PMID- 21842486
TI  - Multimodal biophotonic workstation for live cell analysis.
AB  - A reliable description and quantification of the complex physiology and reactions
      of living cells requires a multimodal analysis with various measurement
      techniques. We have investigated the integration of different techniques into a
      biophotonic workstation that can provide biological researchers with these
      capabilities. The combination of a micromanipulation tool with three different
      imaging principles is accomplished in a single inverted microscope which makes
      the results from all the techniques directly comparable. Chinese Hamster Ovary
      (CHO) cells were manipulated by optical tweezers while the feedback was directly
      analyzed by fluorescence lifetime imaging, digital holographic microscopy and
      dynamic phase-contrast microscopy.

PMID- 21842487
TI  - In vivo measurement of bladder wall oxygen saturation using optical spectroscopy.
AB  - Current diagnosis, follow-up and treatment of patients suffering from bladder
      dysfunction are mainly symptom-targeted. A recently recognized cause of
      continuing bladder function loss is a deteriorated bladder microvasculature.
      Incorporating this aspect into the clinical diagnostic toolbox may improve
      treatment results. Recent developments in the field of optical spectroscopy now
      allow for non-invasive measurement of microvascular blood oxygen saturation in
      living tissue. We have recently reported pre-clinical data that show that this
      marker can be successfully measured in an animal bladder. In the animal model the
      marker differentiated bladders with loss of function from those with normal
      function. In the present paper, we report on the first in vivo measurement of
      this marker in the human bladder, as proof of principle, in the muscle of
      bladders with a normal function.

PMID- 21842488
TI  - Transcriptional profiling in Saccharomyces cerevisiae relevant for predicting
      alachlor mechanisms of toxicity.
AB  - Alachlor has been a commonly applied herbicide and is a substance of
      ecotoxicological concern. The present study aims to identify molecular biomarkers
      in the eukaryotic model Saccharomyces cerevisiae that can be used to predict
      potential cytotoxic effects of alachlor, while providing new mechanistic clues
      with possible relevance for experimentally less accessible eukaryotes. It focuses
      on genome-wide expression profiling in a yeast population in response to two
      exposure scenarios exerting effects from slight to moderate magnitude at
      phenotypic level. In particular, 100 and 264 genes, respectively, were found as
      differentially expressed on a 2-h exposure of yeast cells to the lowest observed
      effect concentration (110 mg/L) and the 20% inhibitory concentration (200 mg/L)
      of alachlor, in comparison with cells not exposed to the herbicide. The datasets
      of alachlor-responsive genes showed functional enrichment in diverse metabolic,
      transmembrane transport, cell defense, and detoxification categories. In general,
      the modifications in transcript levels of selected candidate biomarkers, assessed
      by quantitative reverse transcriptase polymerase chain reaction, confirmed the
      microarray data and varied consistently with the growth inhibitory effects of
      alachlor. Approximately 16% of the proteins encoded by alachlor-differentially
      expressed genes were found to share significant homology with proteins from
      ecologically relevant eukaryotic species. The biological relevance of these
      results is discussed in relation to new insights into the potential adverse
      effects of alachlor in health of organisms from ecosystems, particularly in worst
      case situations such as accidental spills or careless storage, usage, and
      disposal.

PMID- 21842489
TI  - Avoidance, weight loss, and cocoon production assessment for Eisenia fetida
      exposed to C60 in soil.
AB  - Eisenia fetida was used as a model terrestrial organism to assess the potential
      ecotoxicity of molecular pristine C60 in soil. Reproduction (assessed by counting
      cocoon numbers) was hindered only at very high C60 concentrations (5% by weight),
      and C60 (up to 1%) was not avoided and did not hinder earthworm growth. This
      suggests that E. fetida is unlikely to experience acute toxicity as a result of
      C60 occurrence in soil. Whether sublethal toxicity may decrease earthworm
      populations that are chronically exposed to C60 at lower concentrations remains
      to be determined.

PMID- 21842490
TI  - Development of biotic ligand models for chronic manganese toxicity to fish,
      invertebrates, and algae.
AB  - Ecotoxicity tests were performed with fish, invertebrates, and algae to
      investigate the effect of water quality parameters on Mn toxicity. Models were
      developed to describe the effects of Mn as a function of water quality. Calcium
      (Ca) has a protective effect on Mn toxicity for both fish and invertebrates, and
      magnesium (Mg) also provides a protective effect for invertebrates. Protons have
      a protective effect on Mn toxicity to algae. The models derived are consistent
      with models of the toxicity of other metals to aquatic organisms in that divalent
      cations can act as competitors to Mn toxicity in fish and invertebrates, and
      protons act as competitors to Mn toxicity in algae. The selected models are able
      to predict Mn toxicity to the test organisms to within a factor of 2 in most
      cases. Under low-pH conditions invertebrates are the most sensitive taxa, and
      under high-pH conditions algae are most sensitive. The point at which algae
      become more sensitive than invertebrates depends on the Ca concentration and
      occurs at higher pH when Ca concentrations are low, because of the sensitivity of
      invertebrates under these conditions. Dissolved organic carbon concentrations
      have very little effect on the toxicity of Mn to aquatic organisms.

PMID- 21842491
TI  - Strong associations of short-chain perfluoroalkyl acids with serum albumin and
      investigation of binding mechanisms.
AB  - Interactions of perfluoroalkyl acids (PFAAs) with tissue and serum proteins
      likely contribute to their tissue distribution and bioaccumulation patterns.
      Protein-water distribution coefficients (K(PW) ) based on ligand associations
      with bovine serum albumin (BSA) as a model protein were recently proposed as
      biologically relevant parameters to describe the environmental behavior of PFAAs,
      yet empirical data on such protein binding behavior are limited. In the present
      study, associations of perfluoroalkyl carboxylates (PFCAs) with two to 12 carbons
      (C2-C12) and perfluoroalkyl sulfonates with four to eight carbons (C4, C6, and
      C8) with BSA are evaluated at low PFAA:albumin mole ratios and various solution
      conditions using equilibrium dialysis, nanoelectrospray ionization mass
      spectrometry, and fluorescence spectroscopy. Log K(PW) values for C4 to C12 PFAAs
      range from 3.3 to 4.3. Affinity for BSA increases with PFAA hydrophobicity but
      decreases from the C8 to C12 PFCAs, likely due to steric hindrances associated
      with longer and more rigid perfluoroalkyl chains. The C4-sulfonate exhibits
      increased affinity relative to the equivalent chain-length PFCA. Fluorescence
      titrations support evidence that an observed dependence of PFAA-BSA binding on pH
      is attributable to conformational changes in the protein. Association constants
      determined for perfluorobutanesulfonate and perfluoropentanoate with BSA are on
      the order of those for long-chain PFAAs (K(a) ~106/M), suggesting that
      physiological implications of strong binding to albumin may be important for
      short-chain PFAAs.

PMID- 21842492
TI  - Effects of beta-endosulfan on the growth and reproduction of zebrafish (Danio
      rerio).
AB  - Because of persistent organic pollution in aquatic environments, the widely used
      organochlorine pesticide endosulfan, which is a potential endocrine disruptor, is
      expected to pose a significant risk to aquatic organisms. In the present study,
      we explored the potential endocrine-disrupting risk of beta-endosulfan by
      investigating its effect on the growth, reproduction, plasma vitellogenin, and
      organ histology of adult zebrafish. We found that, although beta-endosulfan did
      not significantly affect the growth of zebrafish, it greatly decreased the
      hatching rate, even at a concentration as low as 10 ng/L. Interestingly, the
      decrease of the hatching rate was highly correlated with pathological alterations
      of the testes. Additionally, the values of the gonadosomatic index were
      significantly reduced in female zebrafish treated with 200 ng/L beta-endosulfan,
      which was also closely associated with ovarian histological changes. More
      importantly, a significant increase in the level of vitellogenin was observed in
      all male fish treated with beta-endosulfan. Based on these findings, we conclude
      that beta-endosulfan severely affects the reproductive function of zebrafish and
      the synthesis of vitellogenin in the liver, and thus, beta-endosulfan has a
      serious endocrine disruption function in zebrafish.

PMID- 21842493
TI  - Structure-activity relationship study on the binding of PBDEs with thyroxine
      transport proteins.
AB  - Molecular docking and three-dimensional quantitative structure-activity
      relationships (3D-QSAR) were used to develop models to predict binding affinity
      of polybrominated diphenyl ether (PBDE) compounds to the human transthyretin
      (TTR). Based on the molecular conformations derived from the molecular docking,
      predictive comparative molecular similarity indices analysis (CoMSIA) models were
      developed. The results of CoMSIA models were as follows: leave-one-out (LOO)
      cross-validated squared coefficient q2 (LOO) = 0.827 (full model, for all 28
      compounds); q2 (LOO) = 0.752 (split model, for 22 compounds in the training set);
      leave-many-out (LMO) cross-validated squared coefficient q2 (LMO, two groups) =
      0.723 +/- 0.100 (full model, for all 28 compounds); q2 (LMO, five groups) = 0.795
      +/- 0.030 (full model, for all 28 compounds); and the predictive squared
      correlation coefficient r2(pred)  = 0.928 (for six compounds in the test set).
      The developed CoMSIA models can be used to infer the activities of compounds with
      similar structural characteristics. In addition, the interaction mechanism
      between hydroxylated polybrominated diphenyl ethers (HO-PBDEs) and the TTR was
      explored. Hydrogen bonding with amino acid residues Asp74, Ala29, and Asn27 may
      be an important determinant for HO-PBDEs binding to TTR. Among them, forming
      hydrogen bonds with amino acid residues Asp74 might exert a more important
      function.

PMID- 21842494
TI  - Periadolescent changes of D(2) -AMPA interactions in the rat nucleus accumbens.
AB  - Many aspects of dopamine (DA) systems mature during adolescence. In the nucleus
      accumbens, the modulation of prefrontal cortical synaptic responses by DA becomes
      refined during adolescence with the recruitment of a gamma-amino butyric acid
      (GABA) component. As this GABA component is depolarizing, it remains to be
      determined whether this change affects action potential firing in nucleus
      accumbens neurons. Here we tested whether a D(2) agonist affects AMPA-evoked cell
      firing in slices containing the nucleus accumbens from juvenile (postnatal day,
      PD 28-34) and adult (PD > 60) rats. 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4
      yl)propanoic acid (AMPA) (0.1-0.4 MUM) depolarized nucleus accumbens neurons and
      increased their firing in a dose-dependent manner. The D(2) agonist quinpirole (2
      MUM) had different effects in juvenile vs. adult slices. In the juvenile
      accumbens, quinpirole enhanced AMPA (0.2 MUM) effects on evoked firing in a
      subset of neurons while it had no effect on the rest. In the adult accumbens, the
      D(2) agonist instead attenuated the effect of AMPA on evoked firing, an
      interaction that was blocked by the GABA-A antagonist picrotoxin (50 MUM). Thus,
      D(2) receptors modulate AMPA responses in the nucleus accumbens differently in
      juvenile than adult rats, and the adult effect requires local GABA transmission.
      The incorporation of a GABA component in the modulation of information processing
      in the nucleus accumbens by DA during adolescence may allow for a better contrast
      in cortically activated ensembles.

PMID- 21842495
TI  - New fossils of the oldest North American euprimate Teilhardina brandti
      (Omomyidae) from the paleocene-eocene thermal maximum.
AB  - More than 25 new specimens of Teilhardina brandti, one of the oldest known
      euprimates, are reported from earliest Eocene strata of the southern Bighorn
      Basin, Wyoming. The new fossils include the first upper dentitions, a dentary
      showing the lower dental formula for the first time, and the first postcrania
      ascribed to T. brandti (tarsals and terminal phalanges). The elongated navicular
      and long talar neck suggest that T. brandti was an active arboreal quadruped, and
      the terminal phalanges constitute the oldest evidence for nails in Euprimates.
      Phylogenetic analysis incorporating the new data indicates that T. brandti is
      more derived than T. belgica but less so than T. americana. The hypothesis that
      Teilhardina originated in Asia (T. asiatica) and dispersed westward to Europe (T.
      belgica) and then to North America (T. brandti and T. magnoliana) during the
      earliest Eocene Paleocene-Eocene Thermal Maximum is most consistent with
      available evidence, including the relative age of fossil samples and their stage
      of evolution.

PMID- 21842496
TI  - A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder
      characterized by loss of motor neurons in the brain and spinal cord, leading to
      muscle weakness and eventually death from respiratory failure. ALS is familial in
      about 10% of cases, with SOD1 mutations accounting for 20% of familial cases.
      Here we describe a consanguineous family segregating juvenile ALS in an autosomal
      recessive pattern and describe the genetic variant responsible for the disorder.
      METHODS: We performed homozygosity mapping and direct sequencing to detect the
      genetic variant and tested the effect of this variant on a motor neuron-like cell
      line model (NSC34) expressing the wild-type or mutant gene. RESULTS: We
      identified a shared homozygosity region in affected individuals that spans ~120
      kbp on chromosome 9p13.3 containing 9 RefSeq genes. Sequencing the SIGMAR1 gene
      revealed a mutation affecting a highly conserved amino acid located in the
      transmembrane domain of the encoded protein, sigma-1 receptor. The mutated
      protein showed an aberrant subcellular distribution in NSC34 cells. Furthermore,
      cells expressing the mutant protein were less resistant to apoptosis induced by
      endoplasmic reticulum stress. INTERPRETATION: Sigma-1 receptors are known to have
      neuroprotective properties, and recently Sigmar1 knockout mice have been
      described to have motor deficiency. Our findings emphasize the role of sigma-1
      receptors in motor neuron function and disease.

PMID- 21842497
TI  - Simplified quantification of labile proton concentration-weighted chemical
      exchange rate (k(ws) ) with RF saturation time dependent ratiometric analysis
      (QUESTRA): normalization of relaxation and RF irradiation spillover effects for
      improved quantitative chemical exchange saturation transfer (CEST) MRI.
AB  - Chemical exchange saturation transfer MRI is an emerging imaging technique
      capable of detecting dilute proteins/peptides and microenvironmental properties,
      with promising in vivo applications. However, chemical exchange saturation
      transfer MRI contrast is complex, varying not only with the labile proton
      concentration and exchange rate, but also with experimental conditions such as
      field strength and radiofrequency (RF) irradiation scheme. Furthermore, the
      optimal RF irradiation power depends on the exchange rate, which must be
      estimated in order to optimize the chemical exchange saturation transfer MRI
      experiments. Although methods including numerical fitting with modified Bloch
      McConnell equations, quantification of exchange rate with RF saturation time and
      power (QUEST and QUESP), have been proposed to address this relationship, they
      require multiple-parameter non-linear fitting and accurate relaxation
      measurement. Our work extended the QUEST algorithm with ratiometric analysis
      (QUESTRA) that normalizes the magnetization transfer ratio at labile and
      reference frequencies, which effectively eliminates the confounding relaxation
      and RF spillover effects. Specifically, the QUESTRA contrast approaches its
      steady state mono-exponentially at a rate determined by the reverse exchange rate
      (k(ws) ), with little dependence on bulk water T(1) , T(2) , RF power and
      chemical shift. The proposed algorithm was confirmed numerically, and validated
      experimentally using a tissue-like phantom of serially titrated pH compartments.

PMID- 21842498
TI  - Robust multipoint water-fat separation using fat likelihood analysis.
AB  - Fat suppression is an essential part of routine MRI scanning. Multiecho chemical
      shift based water-fat separation methods estimate and correct for Bo field
      inhomogeneity. However, they must contend with the intrinsic challenge of water
      fat ambiguity that can result in water-fat swapping. This problem arises because
      the signals from two chemical species, when both are modeled as a single discrete
      spectral peak, may appear indistinguishable in the presence of Bo off-resonance.
      In conventional methods, the water-fat ambiguity is typically removed by
      enforcing field map smoothness using region growing based algorithms. In reality,
      the fat spectrum has multiple spectral peaks. Using this spectral complexity, we
      introduce a novel concept that identifies water and fat for multiecho
      acquisitions by exploiting the spectral differences between water and fat. A fat
      likelihood map is produced to indicate if a pixel is likely to be water-dominant
      or fat-dominant by comparing the fitting residuals of two different signal
      models. The fat likelihood analysis and field map smoothness provide
      complementary information, and we designed an algorithm (Fat Likelihood Analysis
      for Multiecho Signals) to exploit both mechanisms. It is demonstrated in a wide
      variety of data that the Fat Likelihood Analysis for Multiecho Signals algorithm
      offers highly robust water-fat separation for 6-echo acquisitions, particularly
      in some previously challenging applications.

PMID- 21842499
TI  - High temporal resolution retrospective motion correction with radial parallel
      imaging.
AB  - A method for motion correction in multicoil imaging applications, involving both
      data collection and reconstruction, is presented. A bit-reversed radial
      acquisition scheme, in conjunction with a rapid self-calibrated parallel imaging
      method, Generalized auto-calibrating partial parallel acquisition (GRAPPA)
      operator for wider radial bands (GROWL), is used to achieve motion correction at
      a high temporal resolution. View-by-view in-plane motion correction is achieved
      in 2D imaging, while 3D motion correction is achieved for every two consecutive
      slice-encoding planes in 3D imaging. In the proposed technique, GROWL contributes
      in two aspects: First, a central k-space circle/cylinder used as the motion-free
      reference is generated from a small number of radial lines/planes; Second,
      undersampled k-space regions resulting from rotation and inconsistent (e.g.
      intraview and nonrigid body) motion can be filled in. When compared with
      navigator-based motion correction methods, the proposed method does not prolong
      scan time and can be applied to short-TR sequences. Magn Reson Med, 2011. (c)
      2011 Wiley-Liss, Inc.

PMID- 21842500
TI  - Comparison of measuring energy metabolism by different (31) P-magnetic resonance
      spectroscopy techniques in resting, ischemic, and exercising muscle.
AB  - Alternate methods to quantify mitochondrial activity or function have been
      extensively used for studying insulin resistance and type 2 diabetes mellitus,
      namely saturation transfer and phosphocreatine (PCr) recovery. As these methods
      are in fact determining different parameters, this study aimed to compare
      saturation transfer results to PCr recovery measurements within the same group.
      Fifteen subjects underwent saturation transfer and ischemic exercise-recovery
      experiments. PCr decrease during ischemia (Q), induced by cuff inflation, served
      as an additional measure of resting ATP (adenosine triphosphate) production. ATP
      synthetic rate (fATP) measured by saturation transfer (0.234 +/- 0.043 mM/s) was
      greater than (Q = 0.0077 +/- 0.0011 mM/s), but correlated well with Q (r = 0.63 P
      = 0.013). Parameters of PCr recovery correlated well with fATP (Q(max,lin) : r =
      0.71, P = 0.003, Q(max,ADP) : r = 0.66, P = 0.007) and Q (Q(max,lin) : r = 0.92,
      P = 0.000002, Q(max,ADP) : r = 0.76, P = 0.001). In conclusion, although
      saturation transfer yields higher ATP synthetic rates than PCr decrease during
      ischemia, their significant correlation indicates that fATP can be used as a
      marker of mitochondrial activity. The finding that both Q and fATP correlate with
      PCr recovery kinetics suggests that skeletal muscle with greater maximal aerobic
      ATP synthetic rates is also metabolically more active at rest. Magn Reson Med,
      2011. (c) 2011 Wiley-Liss, Inc.

PMID- 21842501
TI  - Whole body traveling wave magnetic resonance imaging at high field strength:
      homogeneity, efficiency, and energy deposition as compared with traditional
      excitation mechanisms.
AB  - In 7 T traveling wave imaging, waveguide modes supported by the scanner
      radiofrequency shield are used to excite an MR signal in samples or tissue which
      may be several meters away from the antenna used to drive radiofrequency power
      into the system. To explore the potential merits of traveling wave excitation for
      whole-body imaging at 7 T, we compare numerical simulations of traveling wave and
      TEM systems, and juxtapose full-wave electrodynamic simulations using a human
      body model with in vivo human traveling wave imaging at multiple stations
      covering the entire body. The simulated and in vivo traveling wave results
      correspond well, with strong signal at the periphery of the body and weak signal
      deep in the torso. These numerical results also illustrate the complicated wave
      behavior that emerges when a body is present. The TEM resonator simulation
      allowed comparison of traveling wave excitation with standard quadrature
      excitation, showing that while the traveling wave B +1 per unit drive voltage is
      much less than that of the TEM system, the square of the average B +1 compared to
      peak specific absorption rate (SAR) values can be comparable in certain imaging
      planes. Both systems produce highly inhomogeneous excitation of MR signal in the
      torso, suggesting that B(1) shimming or other parallel transmission methods are
      necessary for 7 T whole body imaging.

PMID- 21842502
TI  - Spatially encoded phase-contrast MRI-3D MRI movies of 1D and 2D structures at
      millisecond resolution.
AB  - This work demonstrates that the principles underlying phase-contrast MRI may be
      used to encode spatial rather than flow information along a perpendicular
      dimension, if this dimension contains an MRI-visible object at only one spatial
      location. In particular, the situation applies to 3D mapping of curved 2D
      structures which requires only two projection images with different spatial phase
      encoding gradients. These phase-contrast gradients define the field of view and
      mean spin-density positions of the object in the perpendicular dimension by
      respective phase differences. When combined with highly undersampled radial fast
      low angle shot (FLASH) and image reconstruction by regularized nonlinear
      inversion, spatial phase-contrast MRI allows for dynamic 3D mapping of 2D
      structures in real time. First examples include 3D MRI movies of the acting human
      hand at a temporal resolution of 50 ms. With an even simpler technique, 3D maps
      of curved 1D structures may be obtained from only three acquisitions of a
      frequency-encoded MRI signal with two perpendicular phase encodings. Here, 3D MRI
      movies of a rapidly rotating banana were obtained at 5 ms resolution or 200
      frames per second. In conclusion, spatial phase-contrast 3D MRI of 2D or 1D
      structures is respective two or four orders of magnitude faster than conventional
      3D MRI.

PMID- 21842503
TI  - Tailored excitation in 3D with spiral nonselective (SPINS) RF pulses.
AB  - Brain images acquired at 3T often display central brightening with spatially
      varying tissue contrast, caused by inhomogeneity in the transmit radiofrequency
      fields used for excitation. Tailored radiofrequency pulses can provide mitigation
      of radiofrequency field inhomogeneity, but previous designs have been unsuitable
      for 3D imaging in rapid pulse sequences. This article presents a nonselective
      pulse design based on a short (1 ms) 3D spiral k-space trajectory that covers low
      spatial frequencies. The resulting excitations are optimized to produce a uniform
      excitation within a specified volume of interest covering the whole brain. B1
      mapping and pulse calculation times were reduced by optimizing in only five
      slices within the brain. The method has been tested with both single and parallel
      transmission: in phantom experiments, normalized root-mean-square error in
      excitation was 0.022 for single and 0.020 for parallel transmission. The
      corresponding results in vivo were 0.066 and 0.055 respectively. A pilot brain
      imaging study using the proposed pulses for excitation within the Alzheimer's
      disease neuroimaging initiative magnetization prepared rapid gradient echo (MP
      RAGE) protocol, yielded excellent image quality with improved signal to noise
      ratio in peripheral brain regions and enhanced uniformity of contrast compared
      with standard excitation. Greatest performance enhancement was achieved using
      parallel transmission, but single channel transmission offers significant
      improvement over standard excitation pulses.

PMID- 21842504
TI  - Heeding the hard lessons of Chernobyl: Japan avoids the worst so far, but experts
      push for long-term monitoring.

PMID- 21842505
TI  - Effect of Candida antarctica lipase B immobilization on the porous structure of
      the carrier.
AB  - A series of poly(GMA-co-EGDMA) resins with identical composition but varying
      particle sizes, pore radii, specific surface areas and specific volumes are
      studied to assess how Candida antarctica lipase B immobilization affects the
      porosity of the copolymer particles. Mercury porosimetry reveals a significant
      change in the average pore size (up to 6.1-fold), the specific surface area (up
      to 3.2-fold) and the specific volume (up to 2.1-fold) of the epoxy resin. A
      similar behaviour is observed for glutaraldehyde-modified epoxy resins. The
      influences of the resin porosity properties on the loading of Candida antarctica
      lipase B during immobilization and on the hydrolytic activity (hydrolysis of p
      nitrophenyl acetate) of the immobilized lipase are studied.

PMID- 21842506
TI  - Functional and highly porous scaffolds for biomedical applications.
AB  - Highly porous functional scaffolds were obtained from linear and cross-linked
      multifunctional poly(epsilon-caprolactone) and poly(L-lactide). The polymers were
      synthesized by ring-opening polymerization of epsilon-caprolactone and L-lactide
      using poly(but-2-ene-1,4-diyl malonate) (PBM) as macroinitiator and stannous 2
      ethylhexanoate. The presence of a double bond in each repeating unit of PBM
      enabled cross-linking of both scaffolds and films. Soft and flexible scaffolds
      were created from cross-linked PBM. The mechanical properties of scaffolds and
      films were evaluated under cyclic conditions, with a focus on the compositions
      and molecular weights. It was obvious that PBM in the polymers and its cross
      linking ability resulted in tunable material characteristics, including an
      increased ability to recover after repeated loading.

PMID- 21842507
TI  - Ultrathin and large-area macroporous polymeric membranes formed through self
      assembly of sub-10 nm elastic nanoparticles.
AB  - A variety of sub-10 nm nanoparticles are successfully prepared by crosslinking of
      polystyrene-b-poly(1,3-butadiene) (PS-b-PB) and polystyrene-b-poly(4-vinyl
      pyridine) (PS-b-P4VP) block copolymer micelles and inverse micelles. Among them,
      the core-crosslinked PS-b-PB micelles can self-assemble into ultrathin (< 10 nm)
      macroporous (pore size <1 um) membranes in a facile way, i.e., by simply drop
      coating the particle solution onto a mica surface. No continuous/porous membranes
      are produced from shell-crosslinked PS-b-PB micelles and both forms of PS-b-P4VP
      micelles. This suggests that the unique structure of the block copolymer
      precursor, including the very flexible core-forming block and the glassy corona
      forming block and the specific block length ratio, directly determines the
      formation of the macroporous membrane.

PMID- 21842508
TI  - Water-free synthesis of polyurethane foams using highly reactive diisocyanates
      derived from 5-hydroxymethylfurfural.
AB  - This paper reports on the synthesis of a new highly reactive diisocyanate monomer
      based on hydroxymethylfurfural. It further describes its catalyst-free conversion
      to linear-chain thermoplastic polyurethanes as well as to cross-linked
      polyurethane foams. In addition, a novel strategy for the synthesis of
      polyurethane foams without the necessity of using water is developed. Nitrogen is
      utilized herein as blowing agent which is formed during Curtius rearrangement of
      a new furan based carboxylic azide into its corresponding diisocyanate. 

PMID- 21842509
TI  - Dual aggregation behavior of porphyrin-cored thiophene dendrimers.
AB  - Two porphyrin-cored thiophene dendrimers T(3T)P and T(7T)P have been successfully
      synthesized and characterized by UV-vis and fluorescence measurements. The self
      assembly of these two water-insoluble free base porphyrins to form both intrinsic
      H- and J-aggregates has been reported for the first time. This intrinsic behavior
      is in contrast to the use of surfactants, dyes, and metal ions to induce
      aggregation behavior on most porphyrin systems. This work emphasizes the
      importance of controlling the size, solvent, and extent of conjugation of
      polythiophene dendron groups in porphyrin systems. These materials may yet be
      applied to polythiophene or porphyrin blend system in energy conversion devices
      with the light-harvesting properties of the polythiophene dendrons.

PMID- 21842510
TI  - Horseradish peroxidase as a catalyst for atom transfer radical polymerization.
AB  - The hemoprotein horseradish peroxidase (HRP) catalyzes the polymerization of N
      isopropylacrylamide with an alkyl bromide initiator under conditions of
      activators regenerated by electron transfer atom transfer radical polymerization
      (ARGET ATRP) in the absence of any peroxide. This is a novel activity of HRP,
      which we propose to name ATRPase activity. Bromine-terminated polymers with
      polydispersity indices (PDIs) as low as 1.44 are obtained. The polymerization
      follows first order kinetics, but the evolution of molecular weight and the PDI
      upon increasing conversion deviate from the results expected for an ATRP
      mechanism. Conversion, M(n) and PDI depend on the pH and on the concentration of
      the reducing agent, sodium ascorbate. HRP is stable during the polymerization and
      does not unfold or form conjugates.

PMID- 21842511
TI  - Electro-active Polymer Actuator Based on Sulfonated Polyimide with Highly
      Conductive Silver Electrodes Via Self-metallization.
AB  - We report here a facile synthesis of high performance electro-active polymer
      actuator based on a sulfonated polyimide with well-defined silver electrodes via
      self-metallization. The proposed method greatly reduces fabrication time and
      cost, and obviates a cation exchange process required in the fabrication of ionic
      polymer-metal composite actuators. Also, the self-metallized silver electrodes
      exhibit outstanding metal-polymer adhesion with high conductivity, resulting in
      substantially larger tip displacements compared with Nafion-based actuators. 

PMID- 21842512
TI  - Atomic force microscopy of microwear traces on Mousterian tools from Myshtylagty
      Lagat (Weasel Cave), Russia.
AB  - Since durable technology emerged between 3.4 and 3.2 million years ago, stone
      tools served as a major material means that hominins used to survive. Determining
      how different lithic tools functioned is a principal question in human evolution.
      The main experimentally based approach to the functional study of lithic
      technology uses stereo and incident-light microscopy, and is known as the Keeley
      Method. Although this method has demonstrated success in linking the morphology
      of microwear traces on flint tools to the function of the tool, there is no
      agreed upon model of how these microwear polishes form. At the same time, the
      characterization of these polishes has been a largely qualitative process.
      Herein, we use the atomic force microscope (AFM) to scan microwear traces on
      Middle Palaeolithic (Mousterian) tools from Weasel Cave, Russia to show
      quantitative data and small scale features of microwear polishes interpreted
      (using the Keeley Method) as due to contact with meat, fresh hide, dry hide,
      bone, wood, and hafting. These results follow those of to the previous AFM study
      on the experimental tools, namely that the meat and dry hide polishes are the
      least developed polishes with smaller changes in roughness and that the bone
      polish and wood polishes are more highly developed polishes and exhibit larger
      changes in roughness.

PMID- 21842514
TI  - A liquid chromatography-tandem mass spectrometry method for the quantitative
      determination of diastereomers of a phosphoramidate nucleotide prodrug (PSI-7851)
      in human plasma.
AB  - A rapid and stereospecific method using high performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) for the separation and determination of PSI
      7851 diastereomers in human K2EDTA plasma has been developed. The analytical
      method involves direct protein precipitation with acetonitrile, followed by
      separation of the diastereomers on a Luna C18 column, positive mode electrospray
      ionization and selected reaction monitoring mode mass spectrometry detection. The
      mobile phase composition and pH were investigated for the resolution of the two
      diastereomers of PSI-7851. The optimized method showed good resolution (R(s)  =
      4.8) within short analysis time (approximately 8 min). The assay range was 5-2500
      ng/mL for both diastereomers using a 1/x2 weighted linear regression analysis for
      standard curve fitting. Replicate sample analysis indicated that intra- and inter
      day accuracy and precision were within +/-15.0%. The recovery of diastereomers
      from human plasma was greater than 85% and no significant matrix effect was
      observed. The method was demonstrated to be sensitive, selective and robust, and
      was successfully used to support clinical studies.

PMID- 21842515
TI  - Sensitive determination of D-lactic acid and L-lactic acid in urine by high
      performance liquid chromatography-tandem mass spectrometry.
AB  - D-lactic acid in urine originates mainly from bacterial production in the
      intestinal tract. Increased D-lactate excretion as observed in patients affected
      by short bowel syndrome or necrotizing enterocolitis reflects D-lactic
      overproduction. Therefore, there is a need for a reliable and sensitive method
      able to detect D-lactic acid even at subclinical elevation levels. A new and
      highly sensitive method for the simultaneous determination of L- and D-lactic
      acid by a two-step procedure has been developed. This method is based on the
      concentration of lactic acid enantiomers from urine by supported liquid
      extraction followed by high-performance liquid chromatography-tandem mass
      spectrometry. The separation was achieved by the use of an Astec ChirobioticTM R
      chiral column under isocratic conditions. The calibration curves were linear over
      the ranges of 2-400 and 0.5-100 umol/L respectively for L- and D-lactic acid. The
      limit of detection of D-lactic acid was 0.125 umol/L and its limit of
      quantification was 0.5 umol/L. The overall accuracy and precision were well
      within 10% of the nominal values. The developed method is suitable for production
      of reference values in children and could be applied for accurate routine
      analysis.

PMID- 21842516
TI  - Anion-exchange HPLC separation of five major rabbit lipoproteins using a
      nonporous diethylaminoethyl-ligated gel with a perchlorate-containing eluent.
AB  - Rabbits are often used as experimental animals in studies of atherosclerosis and
      hyperlipidemia. Although rabbit lipoproteins can be quantitated by sequential
      ultracentrifugation, a simpler and more reproducible method is desirable for
      detailed analyses. The current study describes a method to analyze rabbit
      lipoproteins in plasma by anion-exchange high-performance liquid chromatography
      using a column filled with nonporous, diethylaminoethyl-ligated polymers. A
      solution of NaClO4 was used to adjust the ionic strength of the eluent. The
      method required only 15 MUL of plasma and analysis was completed in 23 min. Five
      lipoprotein fractions (high-density lipoprotein, low-density lipoprotein,
      intermediate-density lipoprotein, very-low-density lipoprotein and chylomicrons)
      were eluted with step-wise increases in a concentration of NaClO4. The post
      column eluate was reacted with an enzymatic reagent to determine total
      cholesterol, and the lipoprotein-cholesterol fraction was calculated according to
      relative peak areas in the chromatogram. The within-day and between-day assay
      coefficients of variation for lipoprotein cholesterol levels ranged between 0.436
      and 7.143% and between 2.905 and 10.526%, respectively. Administering a high-fat
      diet increased lipoprotein-cholesterol concentrations by 6- to 77-fold. The
      method described here was nevertheless able to quantitate levels of lipoprotein
      cholesterol in plasma samples from these rabbits. These results indicate that
      this method may be applied to lipoprotein studies using hyperlipidemic rabbit
      models.

PMID- 21842517
TI  - Head exposure system for a human provocation study to assess the possible
      influence of UMTS-like electromagnetic fields on cerebral blood circulation using
      near-infrared imaging.
AB  - A head exposure setup for efficient and precisely defined exposure of human
      subjects equipped with a near-infrared imaging (NIRI) sensor is presented. In a
      partially shielded anechoic chamber the subjects were exposed to Universal Mobile
      Telecommunications System (UMTS)-like electromagnetic fields (EMF) by using a
      patch antenna at a distance of 4 cm from the head. The non-contact design of the
      exposure setup enabled NIRI sensors to easily attach to the head. Moreover,
      different regions of the head were chosen for localised exposure and simultaneous
      NIRI investigation. The control software enabled the simple adaptation of the
      test parameters during exploratory testing as well as the performance of
      controlled, randomised, crossover and double-blind provocation studies. Four
      different signals with a carrier frequency of 1900 MHz were chosen for the
      exposure: a simple continuous wave signal and three different UMTS signals.
      Furthermore, three exposure doses were available: sham, low (spatial peak
      specific absorption rate (SAR) = 0.18 W/kg averaged over 10 g) and high (spatial
      peak SAR = 1.8 W/kg averaged over 10 g). The SAR assessment was performed by
      measurement and simulation. Direct comparison of measurement and numerical
      results showed good agreement in terms of spatial peak SAR and SAR distribution.
      The variability analysis of the spatial peak SAR over 10 g was assessed by
      numerical simulations. Maximal deviations of -22% and +32% from the nominal
      situation were observed. Compared to other exposure setups, the present setup
      allows for low exposure uncertainty, combined with high SAR efficiency, easy
      access for the NIRI sensor and minimal impairment of test subjects.

PMID- 21842518
TI  - Enhancing and inhibiting effects of benzenediols on chemiluminescence of a novel
      cyclometallated iridium(III) complex.
AB  - A novel chemiluminescence (CL) system, including the cyclometallated iridium(III)
      complex {tris[1-(2,6-dimethylphenoxy)-4-(4-chlorophenyl)phthalazine]iridium},
      potassium permanganate and oxalic acid, is proposed for the determination of
      benzenediols. This method is based on the fact that hydroquinone and catechol
      exhibited an inhibiting effect, while resorcinol exhibited an enhancing effect on
      CL intensity. The optimum conditions for CL emission were investigated. Under
      optimal conditions, the detection limits of hydroquinone, catechol and resorcinol
      were 6.4 * 10(-8), 2.7 * 10(-9) and 8.1 * 10(-7)  mol/L, respectively. The method
      has been successfully applied to the determination of benzenediols in different
      types of water sample. The luminophors of the CL systems were all identified as
      the metal-ligand charge-transfer (MLCT) excited state of the iridium complex.

PMID- 21842519
TI  - Does neoadjuvant chemotherapy reveal disease precluding surgical treatment of
      initially resectable colorectal cancer liver metastases?
AB  - BACKGROUND: The objective of this study is to determine whether neoadjuvant
      chemotherapy reveals occult disease precluding surgical extirpation of initially
      resectable colorectal cancer liver metastases (CRCLM). METHODS: Demographics,
      clinicopathologic tumor characteristics, treatments, and post-operative outcomes
      of patients aged 18-80 years, with one to four initially resectable CRCLM, and
      without concurrent extra-hepatic (EHMD) or previous metastatic disease were
      reviewed. RESULTS: Two hundred and two patients evaluated from 2000 to 2010 met
      study criteria; 88 (43.6%) were given neoadjuvant chemotherapy. Patients treated
      with neoadjuvant chemotherapy were younger (median 58 years vs. 65 years, P =
      0.0096), had shorter disease free interval from resection of primary tumor to
      CRCLM diagnosis (median 0 months vs. 12 months, P < 0.0001), and had more CRCLM
      (median 1 [1-3] vs. 1 [1-2], P = 0.0096) compared to untreated counterparts.
      There were no differences in rates of concurrent EHMD noted intra-operatively and
      not on pre-operative imaging (4.5% vs. 3.5%, P = 0.7290), greater intra
      operatively observed CRCLM compared to pre-operative imaging (25.3% vs. 17.5%, P
      = 0.2449), hepatic resection and/or ablation (97.7% vs. 100.0%, P = 0.9853), or 6
      month disease recurrence after surgical treatment (25.6% vs. 14.9%, P = 0.0882).
      Only two (2.3%) patients treated with neoadjuvant chemotherapy had disease
      progression precluding surgical extirpation. CONCLUSIONS: Neoadjuvant
      chemotherapy for initially resectable CRCLM does not reveal occult disease
      precluding surgical treatment.

PMID- 21842520
TI  - The prognostic value of grade of regression and oncocytic change in rectal
      adenocarcinoma treated with neo-adjuvant chemoradiotherapy.
AB  - BACKGROUND: Pathological staging and regression grading may affect the clinical
      outcome in rectal carcinoma patients treated with neoadjuvant chemoradiation
      (NACRT). Oncocytic change (OC) has also been described in the residual tumor.
      This study assesses the correlation of degree of pathological response and OC
      with clinical outcome. METHODS: Seventy-five cases of rectal adenocarcinoma
      undergoing NACRT followed by surgery were retrospectively analyzed for
      preoperative and post-operative staging, degree of tumor response to NACRT using
      the Dworak Regression score (DR) and Tumor Regression Grading (TRG) systems, as
      well as the proportion of cells showing OC. These parameters were correlated with
      overall survival (OS) and disease-free survival (DFS). RESULTS: Significant
      correlation was found between post-operative T and N stage and OS (P = 0.005 and
      0.002, respectively); and post-operative and preoperative T stage with DFS (P =
      0.002 and 0.02, respectively). Grouping patients by TRG scores (TRG1-3 vs TRG4-5)
      also proved to be a significant independent prognosticator for DFS (P < 0.001).
      The DR score groups and OC (<35% vs. >35%) were not statistically significant
      predictors of clinical outcome. CONCLUSIONS: Post-NACRT T and N staging and the
      TRG system are important prognostic indicators. The presence and extent of OC
      needs to be better understood and further investigated.

PMID- 21842521
TI  - AKT1 polymorphisms and survival of early stage non-small cell lung cancer.
AB  - BACKGROUND AND OBJECTIVES: This study was conducted to investigate the impact of
      polymorphisms in the AKT1 gene on the survival of early stage non-small cell lung
      cancer (NSCLC) patients. METHODS: Three hundred and ten patients with surgically
      resected NSCLC were enrolled. The rs3803300, rs1130214, rs3730358, rs1130233, and
      rs2494732 single nucleotide polymorphisms (SNPs) in the AKT1 gene were
      investigated. The genotype and haplotype associations with overall survival (OS)
      and disease free survival (DFS) were analyzed. RESULTS: The three SNPs
      (rs3803300, rs1130214, and rs2494732) were significantly associated with survival
      outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS
      were decreased in a dose-dependent manner as the number of bad genotypes
      increased (P(trend)  = <1.0 * 10(-4) and 0.001, respectively). Patients with 2
      bad genotypes had a significantly worse OS and DFS compared with those with 0 bad
      genotypes (adjusted hazard ratio (HR) = 3.08, 95% confidence interval (CI) = 1.61
      5.89, P = 0.001; and adjusted HR = 2.04, 95% CI = 1.22-3.43, P = 0.01).
      CONCLUSIONS: These results suggest that the AKT1 polymorphisms could be used as
      prognostic markers for the patients with early-stage NSCLC.

PMID- 21842522
TI  - The prognostic significance of tumor laterality in patients with esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: It has been shown that part of the lymph fluid from the right/dorsal
      side of the esophagus drains directly into the thoracic duct, whereas the lymph
      fluid from the left/ventral side has to pass through lymph nodes before entering
      the duct. We hypothesized that patients with right/dorsal tumors have a poorer
      prognosis than those with left/ventral tumors because cancer cells from the
      right/dorsal quadrant may easily enter the systemic circulation. METHODS: A total
      of 77 patients with pT1b- or pT2-staged cancers treated by esophagectomy without
      neoadjuvant treatment were enrolled in this study. Tumor laterality was
      determined endoscopically. RESULTS: The tumor location was right/dorsal in 45
      patients and left/ventral in 32. The right/dorsal group had a lower lymph node
      stage (pN, P = 0.043) and shorter disease-free survival (P = 0.027). Multivariate
      analysis demonstrated that tumor laterality [hazard ratio (HR): 0.052, 95%
      confidence interval (CI): 0.007-0.37, P = 0.003], pN (HR: 3.8, 95% CI: 1.7-9.1, P
      = 0.001), and tumor size (HR: 1.02, 95% CI: 1-1.04, P = 0.02) were independent
      prognostic factors. CONCLUSIONS: This is the first study to demonstrate a
      relationship between tumor laterality and prognosis in patients with esophageal
      squamous cell carcinoma. These findings need to be validated in a prospective
      large study.

PMID- 21842523
TI  - Supercapacitive energy storage and electric power supply using an aza-fused pi
      conjugated microporous framework.

PMID- 21842524
TI  - Antioxidant activities and functional properties of grass carp (Ctenopharyngodon
      idellus) protein hydrolysates.
AB  - BACKGROUND: Grass carp, with an annual production exceeding 4 * 10(6) t in China
      in 2009, has not been developed into a high-value product. In this study the
      antioxidant activities and functional properties of grass carp protein
      hydrolysates prepared with Alcalase 2.4L (HA) and papain (HP) were investigated.
      The hydrolysate with strongest radical-scavenging activity and reducing power was
      assessed further for changes in its antioxidant activity during simulated
      gastrointestinal digestion. RESULTS: As the degree of hydrolysis (DH) increased,
      the metal-chelating activity of both HA and HP increased while their reducing
      power and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH(*) )-scavenging activity
      decreased (P < 0.05). At the same DH, HP possessed higher DPPH(*) -scavenging
      activity and reducing power than HA (P < 0.05). The metal-chelating activity of
      HP with 10% DH was significantly increased after in vitro gastrointestinal
      metabolism (P < 0.05). Regarding their functional properties, all hydrolysates
      were more than 81% soluble over a wide range of pH (3-8). At the same DH, HP
      showed higher emulsion activity index but lower solubility and foaming capacity
      than HA. CONCLUSION: Grass carp protein hydrolysates showed high solubility over
      a wide pH range and could be used as natural antioxidants in food systems.

PMID- 21842525
TI  - Environmental conditions affect semolina quality in durum wheat (Triticum
      turgidum ssp. durum L.) cultivars with different gluten strength and gluten
      protein composition.
AB  - BACKGROUND: Sowing time may impact semolina and pasta cooking quality by changing
      the environmental conditions during grain filling. The effect of an optimum and a
      delayed sowing time on semolina quality was studied by comparing six cultivars
      under irrigation, in order to isolate temperature from drought effects. RESULTS:
      Protein content was higher in the old cultivars and in the late sowings,
      according to the number of days with temperature between 30 and 40  degrees C
      during ripening. Gluten index increased as temperature rose to a threshold of
      about 30  degrees C, then decreased under higher temperatures. Mixograph
      parameters were less sensitive to high temperatures. Gliadin:glutenin correlated
      with gluten strength. Spaghetti firmness and protein content were positively
      correlated independently of sowing date. Cultivars Trinakria and Cappelli had the
      highest spaghetti firmness (900 and 828 g). CONCLUSIONS: Late sowings may
      represent a way of increasing pasta cooking quality whenever they place grain
      filling under thermal conditions able to increase protein percentage, although
      the accompanying decrease in yield may represent a drawback in environments prone
      to drought stress during ripening. The lower protein percentages of modern durum
      wheat cultivars under conventional sowing times results in a lower pasta cooking
      quality despite higher gluten strength.

PMID- 21842526
TI  - Developmental studies of transgenic maize expressing Cry1Ab on the African stem
      borer, Busseola fusca; effects on midgut cellular structure.
AB  - BACKGROUND: Busseola fusca is a major pest of maize in Africa but unfortunately
      is difficult to control using chemical insecticides. Insect-resistant transgenic
      crops may provide an alternative viable strategy to control this pest. RESULTS:
      Recombinant Cry1Ab (1%) reduced larval weight by 60% over the trial period, while
      larval weight in the control group increased by 25%; no effects on mortality were
      observed. Insect survival, developmental rate and pupal and adult weight were
      significantly reduced (P < 0.05) on maize expressing Cry1Ab (MON810) compared
      with the non-transformed parental line. These differences were more pronounced
      with second-instar larvae than with third-instar larvae. Leaf area consumed by
      Bacillus thuringiensis (Bt)-fed larvae was significantly lower (0.5 cm(2) larva(
      1) day(-1)) compared with the area consumed by control-fed insects (3.3 cm(2)
      larva(-1) day(-1)). EM studies revealed that consumption of Bt maize
      deleteriously affected gut integrity. Effects were observed in columnar cells of
      the midgut epithelium, with the cytoplasm becoming highly vacuolated; the
      microvilli were disorganised, the mitochondria were abnormal and there was an
      increase in the number of lysosomal bodies. The rough endoplasmic reticulum had
      also become dilated. CONCLUSION: This study confirms the potential for Bt maize,
      when used as part of an IPM programme, for control of B. fusca.

PMID- 21842527
TI  - Systemic nematicidal activity of fluensulfone against the root-knot nematode
      Meloidogyne incognita on pepper.
AB  - BACKGROUND: Fluensulfone, a new nematicide of the fluoroalkenyl group, has proved
      to be very effective in controlling root-knot nematodes, Meloidogyne spp., by
      soil application. The systemic activity of this compound against M. incognita on
      peppers via soil drenching and foliar spray was evaluated. RESULTS: Root
      application of fluensulfone via soil drenching showed slight and no nematode
      control activity when applied 4 and 10 days, respectively, after inoculation. A
      single foliar spray of peppers with a fluensulfone solution at 3.0 g L(-1) prior
      to inoculation reduced the galling index by 80% and the number of nematode eggs
      by 73-82% of controls. The reduction in these parameters by fluensulfone was much
      higher than that obtained with oxamyl or fenamiphos at the same concentration.
      This activity was also observed when the plants were sprayed 21 days before
      inoculation. A series of experiments suggested that foliar spray with
      fluensulfone prior to inoculation reduces nematode invasion. However, foliar
      spray after inoculation did not inhibit nematode development inside roots.
      CONCLUSION: Fluensulfone showed relatively high nematode control activity when
      sprayed on the foliage before inoculation. Fluensulfone may be used as a foliar
      application, in addition to soil application, for root-knot nematode control.

PMID- 21842528
TI  - What have the mechanisms of resistance to glyphosate taught us?
AB  - The intensive use of glyphosate alone to manage weeds has selected populations
      that are glyphosate resistant. The three mechanisms of glyphosate resistance that
      have been elucidated are (1) target-site mutations, (2) gene amplification and
      (3) altered translocation due to sequestration. What have we learned from the
      selection of these mechanisms, and how can we apply those lessons to future
      herbicide-resistant crops and new mechanisms of action? First, the diversity of
      glyphosate resistance mechanisms has helped further our understanding of the
      mechanism of action of glyphosate and advanced our knowledge of plant physiology.
      Second, the relatively rapid evolution of glyphosate-resistant weed populations
      provides further evidence that no herbicide is invulnerable to resistance. Third,
      as new herbicide-resistant crops are developed and new mechanisms of action are
      discovered, the weed science community needs to ensure that we apply the lessons
      we have learned on resistance management from the experience with glyphosate.
      Every new weed management system must be evaluated during development for its
      potential to select for resistance, and stewardship programs should be in place
      when the new program is introduced.

PMID- 21842529
TI  - Root-zone temperature and nitrogen affect the yield and secondary metabolite
      concentration of fall- and spring-grown, high-density leaf lettuce.
AB  - BACKGROUND: Understanding the effects of temperature and nitrogen levels on key
      variables, particularly under field conditions during cool seasons of temperate
      climates, is important. Here, we document the impact of root-zone heating and
      nitrogen (N) fertility on the accumulation and composition of fall- and spring
      grown lettuce biomass. A novel, scalable field system was employed. RESULTS:
      Direct-seeded plots containing a uniform, semi-solid, and nearly stable rooting
      medium were established outdoors in 2009 and 2010; each contained one of eight
      combinations of root-zone heating (-/+) and N fertility (0, 72, 144, and 576 mg
      day(-1)). Root-zone heating increased but withholding N decreased biomass
      accumulation in both years. Low N supplies were also associated with greater
      anthocyanin and total antioxidant power but lower N and phosphorus levels. Tissue
      chlorophyll a and vitamin C levels tracked root-zone temperature and N fertility
      more closely in 2009 and 2010, respectively. CONCLUSIONS: Experimentally imposed
      root-zone temperature and N levels influenced the amount and properties of fall-
      and spring-grown lettuce tissue. Ambient conditions, however, dictated which of
      these factors exerted the greatest effect on the variables measured.
      Collectively, the results point to the potential for gains in system
      sustainability and productivity, including with respect to supplying human
      nutritional units.

PMID- 21842530
TI  - [Analysis of the complete mitochondrial genome sequence of Pielomastax zhengi].
AB  - The complete mitochondrial genome sequence of Pielomastax zhengi was determined
      by using long PCR and conserved primer walking approaches. The results showed
      that the entire mitochondrial genome of Pielomastax zhengi is 15 602 bp long with
      A+T content of 71.8%. All 37 genes are conserved in the positions observed in
      those of Locusta migratoria. All the genes are closely assembled by leaving 10
      intergenic spacers in between. Those intergenic spacers are 47 bp in total
      (excluding the A+T rich region), with individual size ranges from 1 bp to 20 bp.
      In addition, there are a total of 52 bp overlapping sequences among 14 genes,
      ranging from 1-8 bp. All protein-coding genes start with a typical initiation
      codon in insects, ATN. Twelve protein-coding genes use the usual TAA and TAG
      termination codons, whereas, the ND5 genes have an incomplete termination codon
      (T). Except the tRNASer (AGN), whose DHU arm is absent; all the other 21 tRNA
      genes have typical clover-leaf secondary structures. But in Pielomastax zhengi,
      the secondary structures of five tRNA (tRNA(Cys), tRNA(Lys), tRNA(Phe),
      tRNA(Pro), tRNA(Arg)) genes can not be predicted by the conventional methods as
      they have only 3-4, rather than 5 base pairs in the TpsiC arm, while, the
      tRNA(Lys) and tRNA(Arg) have only 4 base pairs in the anticode arm. The predicted
      secondary structures of lrRNA and srRNA have 6 domains with 44 helices and 3
      domains with 30 helices, respectively. The results of the rRNA secondary
      structure comparison showed that Pielomastax zhengi is more closely related with
      Locusta migratoria tibetensis than Ruspolia dubia. Like most insects, the
      mitochondrial genome of Pielomastax zhengi has a non-coding A+T rich region
      containing a polythymidine stretch, which may be involved in the replication
      and/or translation initiation of other genes.

PMID- 21842531
TI  - [Microsatellite analysis of genetic variation of the oriental river prawn
      Macrobrachium nipponense in Qiantang River].
AB  - Genetic diversity and genetic structure of 7 wild stocks of oriental river prawn
      Macrobrachium nipponense in Qiantang River, i.e. Wen-yan, Fu-yang, Chang-kou,
      Tong-lu, Xin-an-jiang, She-xian and Xiu-ning, were investigated using 10
      microsatellite DNA markers. The result showed that all the 10 loci were highly
      polymorphic. There was a trend that the level of genetic diversity of wild stocks
      in downstream and midstream were higher than the upstream ones'. Sign test and
      Wilcoxon sign rank test results showed that the stocks in Qiantang River had no
      bottleneck effect, and the number of stocks had not declined recently. F(ST)
      among stocks ranged from 0.0201 to 0.1069. Analysis of molecular variance (AMOVA)
      revealed that a higher portion (93.48%) of variations existed within individuals,
      while lower portion (6.52%) existed among stocks. F(ST) and AMOVA analysis across
      all stocks and loci indicated the medium level of divergence among the stocks.
      The NJ clustering tree based on D(A) genetic distance demonstrated that the
      stocks of adjacent geographical position clustered together. 413 individuals
      obtained from six wild stocks could be divided into two potential populations
      based on the genetic structure. This study demonstrated that genetic diversity
      and genetic structure of M. nipponense stocks were relevant to geographical
      position where they survived.

PMID- 21842532
TI  - Cloning and expression analysis of a long type peptidoglycan recognition protein
      (PGRP-L) from Xenopus tropicalis.
AB  - Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition
      receptors (PRRs) of the immune system, which bind and hydrolyze bacterial
      peptidoglycan. Here, a long type PGRP (PGRP-L) was first cloned in the lower
      vertebrate species Xenopus tropicalis (Xt). The XtPGRP-L possessed a conserved
      genomic structure with five exons and four introns. The alignment and
      phylogenetic analysis indicated that XtPGRP-L might be a type of amidase-like
      PGRP. The 3-D model showed that XtPGRP-L possessed a conserved structure compared
      with the Drosophila PGRP-Lb. During embryonic development, XtPGRP-L was not
      expressed until the 72 h tadpole stage. In adult tissues, it was strongly
      expressed in the liver, lung, intestine, and stomach. Furthermore, after LPS
      stimulation, the expression of XtPGRP-L was up-regulated significantly in the
      liver, intestine and spleen, indicating that XtPGRP-L may play an important role
      in the innate immunity of Xenopus tropicalis.

PMID- 21842533
TI  - [Expression of Bm-TFF2 mutants in Escherichia coli and their cell migration
      promoting activity].
AB  - Bm-TFF2, a trefoil factor from the large-webbed bell toad (Bombina maxima), can
      stimulate cell migration and inhibit cell apoptosis. To study the structure
      function relationship of Bm-TFF2, we constructed wild-type and mutated Bm-TFF2
      plasmids and expressed recombinant proteins in E. coli. The wild-type Bm-TFF2
      gene encoding mature peptide was obtained by RT-PCR, while the N-terminal, C
      terminal and two arginine mutated Bm-TFF2 clones were constructed, and ligated
      into pET-32a(+) expression vectors. The fusion proteins were induced by IPTG at
      37 Degrees Celsius. The mutant Bm-TFF2 fusion proteins expressed mainly in the
      inclusion bodies. The mutant (TRX)/Bm-TFF2 could be purified by using Ni(2+)
      chelating chromatography and reverse-phase HPLC from the inclusion body
      supernatant. The fusion proteins were analyzed by SDS-PAGE and Western blotting.
      The yield of mutant Bm-TFF2 fusion proteins of above 95% purity was about 20
      mg/L. All three recombinant mutant proteins can promote the migration of AGS
      cells in a dose-dependent manner with no obvious activity difference.

PMID- 21842534
TI  - Identification of Z-OTU protein during zebrafish oogenesis and early
      embryogenesis.
AB  - Zebrafish (Danio rerio) Z-OTU, containing OTU and TUDOR domains, was predicted to
      be a member of OTU-related protease, a family of the deubiquitylating enzymes
      (DUBs). A previous report from our laboratory clearly describes the expression
      patterns of z-otu mRNA. Here, we characterized the Z-OTU protein during zebrafish
      oogenesis and early embryogenesis. After prokaryotic expression, the recombinant
      protein of the OTU domain and GST was purified and injected into rabbits to
      obtain the polyclonal antibody-anti-Z-OTU, which was used for
      immunohistochemistry in zebrafish ovaries and embryos. Interestingly, obvious
      differences existed between the expression patterns of z-otu mRNA and its protein
      during oogenesis and early embryogenesis. In stage I oocytes, z-otu mRNA was
      detected in cytoplasm while its protein existed in the germinal vesicle. In
      addition, its protein was distributed during entire oogenesis, while mRNA was not
      detected in oocytes at stage IV or mature oocytes. The z-otu mRNA disappeared
      after midblastula transition (MBT) and its protein gradually decreased after this
      stage. We inferred that Z-OTU protein, like other OTU-related protease with DUB
      activity, was required for germinal vesicle breakdown of oocytes during meiosis,
      germinal vesicle migration, and embryo cleavage maintenance.

PMID- 21842535
TI  - Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus
      monkey embryonic stem cells.
AB  - Rhesus monkey embryonic stem (rES) cells have similar characteristics to human ES
      cells, and might be useful as a substitute model for preclinical research. Notch
      signaling is involved in the formation of bile ducts, which are composed of
      cholangiocytes. However, little is known about the role of Notch signaling in
      cholangiocytic commitment of ES cells. We analyzed the effect of Notch signaling
      on the induction of cholangiocyte-like cells from rES cells. About 80% of
      definitive endoderm (DE) cells were generated from rES cells after treatment with
      activin A. After treatment with BMP4 and FGF1 on matrigel coated wells in serum
      free medium, rES-derived DE gave rise to cholangiocyte-like cells by expression
      of cholangiocytic specific proteins (CK7, CK18, CK19, CK20, and OV-6) and genes
      (GSTPi, IB4, and HNF1beta). At the same time, expression of Notch 1 and Notch 2
      mRNA were detected during cell differentiation, as well as their downstream
      target genes such as Hes 1 and Hes 5. Inhibition of the Notch signal pathway by L
      685458 resulted in decreased expression of Notch and their downstream genes. In
      addition, the proportion of cholangiocyte-like cells declined from approximately
      90% to approximately 20%. These results suggest that Notch signaling may play a
      critical role in cholangiocytic development from ES cells.

PMID- 21842536
TI  - Metabolism and thermoregulation between Mrs Hume's Pheasant (Syrmaticus humiae)
      and Elliot's Pheasant (S. ellioti).
AB  - To understand metabolic adaptations, the basal metabolic rate (BMR) of Mrs Hume's
      Pheasant (Syrmaticus humiae) and Elliot's Pheasant (Syrmaticus ellioti) were
      investigated. Metabolic rate (MR), body temperature (T(b) ) and thermal
      conductance (C) were determined in both species at a temperatrue range of 5-35
      Degrees Celsius, respectively. Oxygen consumption was measured with a closed
      circuit respirometer. The thermal neutral zones (TNZ) were 24.5-31.6 Degrees
      Celsius, and 23.0-29.2 Degrees Celsius, respectively. With a temperature range of
      5-35 Degrees Celsius, Mrs Hume's Pheasant and Elliot's Pheasant could maintained
      stable T(b) at a mean of (40.47 +/- 0.64) and (40.36 +/- 0.10) Degrees Celsius,
      respectively. Mean BMRs within TNZs were (1.36 +/- 0.84) mLO2/(g.h) for Mrs
      Hume's Pheasant and (2.03 +/- 0.12) mLO2/(g.h) for Elliot's Pheasant, which were
      77% and 86% of the expected value based on their body mass, respectively. Thermal
      conductance of Mrs Hume's Pheasant and Elliot's Pheasant were (0.12 +/- 0.01) and
      (0.17 +/- 0.01) mLO2/(g.h.Degrees Celsius), below the lower critical temperature,
      respectively, which were 119% and 124% of the expected value based on their body
      mass, respectively. The ecophysiological characteristics of these species were
      low metabolic rate, high body temperature, and high thermal conductance, which
      allow both species to better adapt to the warmer climate environment in south
      China.

PMID- 21842537
TI  - Afferent and efferent pathways in the visual system of the freshwater snail
      Planorbarius corneus.
AB  - Afferent and efferent neural elements of the retina and central ganglia in the
      freshwater snail Planorbarius corneus were labelled using retrograde transport of
      neurobiotin through the optic nerve. Axons of at least some photoreceptor cells
      become direct contributors to the optic nerve as no synaptic junctions could be
      detected. The processes enter the cerebral ganglion and form a dense bundle of
      thin afferent fibres, the so-called optical neuropil. Efferent neurons were
      revealed in all ganglia, except the buccal ones. Some of the ascending axons
      branch in the cerebral ganglia, cross the cerebro-cerebral commissure, reach the
      contralateral eye and form arborizations in the eye cup. Some efferent neurons
      send axons to different peripheral nerves as well: n.n. intestinalis, pallialis
      dexter, pallialis sinister internus et externus. Serotonin- and FMRF-amide-ergic
      fibres were revealed in the optic nerve. These fibres belong to those central
      neurons which send their axons to the ipsilateral eye only. They form abundant
      varicoses in the eye cup and nuclear layer of the retina, and possibly help to
      regulate retinal sensitivity to light.

PMID- 21842538
TI  - [A traumatic brain injury model for distinguishing between transplanted neural
      cells and host cells in vivo].
AB  - To perform electrophysiological recording and other investigations on
      transplanted neural cells in vivo, we used mechanical damage to establish a
      special traumatic brain injury model that could distinguish transplanted cells
      from host cells. The morphology of the trauma-induced holes in the cortex of the
      rat brain was regular. The model was stable and repeatable. Neural stem cells
      were transplanted into the trauma-induced hole, and were able to survive for a
      long time. Most of the transplanted cells differentiated into neurons, and only a
      small amount turned into glia cells. There was a clear boundary between the host
      cells and the transplanted cells. Single cell electrophysiological recording on
      transplanted neural cells were detected in vivo. This study established a stable
      and repeatable traumatic brain injury model, which could be used to conduct in
      vivo electrophysiological recording research on transplanted neural cells.

PMID- 21842539
TI  - [Impairment effects of tail suspension stress on spatial memory and its reversal
      learning in mice].
AB  - Present work investigated the effects of tail suspension stress (TSS) on spatial
      memory acquisition, consolidation, and its reversal learning in mice. Eighty-one
      adult male KM mice were divided into four groups (each group including a TSS
      subgroup and its control subgroup): absolute spatial memory acquisition and
      consolidation groups (group AA and CA); relative spatial memory acquisition and
      consolidation groups (group AR and CR). TSS (20 min) was performed immediately
      before (acquisition) or after (consolidation) a daily training. Results showed
      that there was no significant difference between control animals and TSS animals
      in each group in early spatial memory training days (5-8 d of training). Along
      with training, the performance of control animals improved significantly, but the
      performance of TSS animals improved slightly (group AA, CA and AR) or even did
      not change (group CR) (P<0.01). Reversal learning was also impaired in TSS
      animals (P<0.01). The results indicated that TSS could impair spatial memory
      acquisition, consolidation and reversal learning (especially the relative spatial
      memory consolidation and its reversal learning) in mice.

PMID- 21842540
TI  - [Effects of Pinus armandii seed size on rodents caching behavior and it's spatio
      temporal variations].
AB  - Pinus armandii, a native pine species, has large (about 300 mg), wingless seeds,
      and distributes from central to western China at an altitude of 1000-3300 m. To
      determine how the seed size affects rodents caching behavior, tagged seed
      releasing and tracking experiments were conducted at 3 sites in Northwest Yunnan
      province in 2006 and 2007. Our data indicated that for all sites and both years,
      compared with the smaller seeds, the proportions of cached large seeds were
      significantly higher, whereas the consumed ones were significantly lower.
      Meanwhile, the mean and maximum values of caching distances were also
      significantly increased in large seeds. Seed fate was different between the two
      years and within the three sites as there have different rodent community
      compositions.

PMID- 21842541
TI  - Behavioral migration diversity of the Yangtze River Japanese Eel, Anguilla
      japonica, based on otolith Sr/Ca ratios.
AB  - The Yangtze River estuary is the main production area of Anguilla japonica in
      China, as well as the only existing fishery area for adult eels. Japanese eels
      are distributed in the main rivers and many tributaries from the Yangtze River
      estuary to the upper Jinsha River, which extend to nearly 3 000 km. However,
      their migration behaviors remain relatively unknown. We analyzed the biological
      characteristics of 153 specimens of silver eels collected from the Jingjiang
      section of Yangtze River (31(o)30'N, 120(o)42'E) between September and November,
      2008, and tested the sagittal Sr/Ca ratios of 27 specimens. Among the 153
      specimens examined, 85 were female and 68 were male, which translated to a female
      male ratio of 1 : 0.8. The ages of the female specimens ranged from 3 to 7 a
      (average 5.52) with an average total length (TL) of (669 +/- 80) mm, average body
      weight (BW) of (555 +/- 229)g, average condition factor of 1.77 +/- 0.22, and
      average gonad somatic index (GSI) of 1.32 +/- 0.31. The ages of the males ranged
      from 3 to 5 a (average:4.38) with an average TL of (518 +/- 51) mm, average BW of
      (234 +/- 76) g, average condition factor of 1.62 +/- 0.18, and average GSI of
      0.21 +/- 0.11. All biological parameters of females were significantly larger
      than those of the male specimens (P<0.05). According to the average Sr/Ca ratio
      (7.99 +/- 1.05) * 10(-3) of the elver mark of sagitta, 17 individuals (62.96%)
      were river eels and 10 individuals (37.04%) were estuarine eels. Of 16 females,
      13 individuals (81.25%) were river eels and 3 were estuarine eels, while of 11
      males, 36.36% were river eels and 63.64% were estuarine eels. The analysis on
      Sr/Ca ratios for every growth layer group (GLG) indicated there were no
      significant differences between second-age males and females. However,
      significant differences were observed between the third-age, fourth-age, and
      migration-age male and female specimens. This was likely related to the fact that
      second-age eels of both sexes stay in the same inhabitation waters; however, as
      they grow older, they move to different areas.

PMID- 21842542
TI  - Visual modeling reveals cryptic aspect in egg mimicry of Himalayan Cuckoo
      (Cuculus saturatus) on its host Blyth's Leaf Warbler (Phylloscopus reguloides).
AB  - Brood parasitism and egg mimicry of Himalayan Cuckoo (Cuculus saturatus) on its
      host Blyth's Leaf Warbler (Phylloscopus reguloides) were studied in south-western
      China from April to July 2009. The cuckoo laid a white egg with fine brown
      markings on the blunt end. The eggs were conspicuously bigger than the host's
      own, with 2.06 g in mass and 1.91 cm(3) in volume. Visual modeling showed that
      the cuckoo eggs, which from the human eye appeared to mimic the host eggs to a
      great extent, were completely different from the host eggs in both hue and
      chroma. The characters of the Himalayan Cuckoo nestling, reported for the first
      time, included two triangular and black patches on its gape, which appeared from
      four days old and became darker with age and growth. While this character also
      exists in nestlings of Oriental Cuckoo (C. optatus), it has not been found for
      other Cuculus species. Our results reveal cryptic aspects in the cuckoo-host egg
      color matching, which are not visible to the naked human eye, and indicate that
      high mimetic cuckoo eggs rejected by hosts, as determined by human observers in
      previous studies, might not be mimetic as birds see them.

PMID- 21842543
TI  - Acoustic characteristics of the tiger frog, Hoplobatrachus rugulosus, during the
      breeding season.
AB  - We recorded and described the calls and acoustic characteristics of the male
      tiger frog, Hoplobatrachus rugulosus, in an artificial pond during mating season.
      Spectral and temporal call parameters, along with call intensity were analyzed.
      Three harmonics were distinguishable from the spectrogram. Four patterns of
      dominant frequency were found in calls produced late at night, i.e, 3 patterns in
      the first harmonic (located in 500 Hz section, 700 Hz section, and 800 Hz section
      respectively) and 1 in the second harmonic (located in 1 800 Hz section). Call
      duration, call duty cycle, call intensity, and pulse rate were highly variable
      among different patterns of dominant frequency. These call properties could
      provide valuable evidence for further ecological study of this species.

PMID- 21842544
TI  - Localization of stationary pronuclei during conjugation of Paramecium as
      indicated by immunofluorescence staining.
AB  - After the third prezygotic division during conjugation of Paramecium caudatum,
      migratory and stationary pronuclei are produced. The migratory pronuclei remain
      in the paroral region tightly against the conjugating boundaries; while the
      stationary pronuclei are located beside the migratory pronuclei. To date,
      however, it is not clear what causes this close side-by-side localization between
      migratory and stationary pronuclei. In the current study, immunofluorescence
      staining with monoclonal antibody of anti-alpha tubulin indicated that ''U'' or
      ''V'' shaped spindles connected the migratory and stationary pronuclei during the
      third prezygotic division. This observation accounts for the close localization
      between these two types of pronuclei.

PMID- 21842545
TI  - Podcasting as an instructional supplement to online learning: a pilot study.
AB  - There is increasing interest in the use of mobile technologies for nursing
      educational purposes in academic settings, but few evaluative studies exist.
      Understanding the best use of podcasting during distance learning is basic for
      instructional design. This pilot study compared online reading to a supplementary
      podcast to determine graduate nursing students' preferences and usage. Results
      indicated that students did not download the podcast to a mobile device but
      multitasked while listening. The podcast and the readings were equally supported
      as important by nursing students. Podcasting in distance-accessible courses may
      engage students by providing a human voice and thus a better virtual connection.
      Podcasting is only one method of knowledge acquisition; distance learning courses
      should consider providing multiple learner-centered delivery methods, given the
      variety of learning styles.

PMID- 21842546
TI  - Tweet, post, share--a new school of health communication.

PMID- 21842547
TI  - Why HIV leads infectious disease priorities.

PMID- 21842548
TI  - Malignant catarrhal fever in cows due to ovine herpesvirus type 2.

PMID- 21842549
TI  - Blood clotting and coagulation factors: the work of Yale Nemerson. 1980, 1982.
AB  - After developing a blood disorder, Yale Nemerson became interested in hematology.
      This led to his lifelong study of thrombogenic tissue factor and to his
      contributions to developing the modern theory of blood coagulation. The two
      Classic papers reprinted here detail some of Nemerson's studies on coagulation
      factors IX and VII.

PMID- 21842550
TI  - Trans-Atlantic debate: Debate regarding the best surgical option for type IV
      thoracoabdominal aortic aneurysms.

PMID- 21842551
TI  - Decriminalisation of drugs.

PMID- 21842552
TI  - Surgery by flashlight as Joplin team operates through tornado.

PMID- 21842553
TI  - [Benefits and difficulties of combined antibiotic therapy].

PMID- 21842554
TI  - [Eliminating healthcare-associated infections].

PMID- 21842555
TI  - Largest ever DNA methylation dataset for breast cancer completed.
AB  - DNA methylation dataset for human breast tumor tissue could aid in the diagnosis
      of the disease.

PMID- 21842556
TI  - Preface to Renata Gaddini's Italian translation of "The Family and Individual
      Development".

PMID- 21842557
TI  - The precursors of transitional objects and phenomena.

PMID- 21842558
TI  - Creativity and the "nebulous" in Winnicott.

PMID- 21842559
TI  - "Bildung" or the formation of the psychoanalyst.
AB  - As a number of Sigmund Freud's patients and followers in the crucial formative
      years of psychoanalysis were from the German- and Austrian-Jewish educated class,
      and as the then prestigious humanistic tradition was considered essential for the
      formation of analysts, the paper gives a historical account of various discourses
      of "Bildung"so as to explain the particularity of the Freudian psychoanalyst.
      Amongst others, his humanistic aspirations are compared with Thomas Mann's re
      examination of the tradition of "Bildung." It is argued that Freud's specific
      cultural milieu -- the German-Jewish assimilation -- conditioned the form his
      psychological knowledge adopted and the way the analyst was fashioned: the demand
      of breaking away from one's alienating individuality by the objectifying effect
      of a symbolic system. The Freudian ideals of purity and neutrality, the Freudian
      method of self-formation, and the Freudian expert subject thus produced were
      historically and culturally determined and thus subject to variation.

PMID- 21842560
TI  - Closing the gap: nurses and midwives making a difference.

PMID- 21842561
TI  - Nurses and midwives closing the gap  in Indigenous Australian health care.

PMID- 21842562
TI  - How can nursing and midwifery help close the gap in Indigenous health indicators?

PMID- 21842563
TI  - Naming and framing Indigenous  health issues.

PMID- 21842564
TI  - Epilogue.

PMID- 21842565
TI  - The early relationship between Sigmund Freud and Isidor Sadger: a dream (1897)
      and a letter (1902).
AB  - Proceeding from Wittels' comment that Isidor Sadger's essay "The miracle of the
      thinking protein" (1897a) was the day residue for Freud's dream of the norekdal
      style, I suggest that the dream was dreamt between February/April 1897 and autumn
      1897. I go on to consider which of Sadger's publications on Ibsen could have been
      the second day residue for Freud's dream. Against the background of Freud and
      Sadger's relationship in the 1890s, I examine what it was about Sadger's essay
      that could have precipitated the dream. Flechsig's basic conception of the
      connection between brain and mind and Sadger's pre-analytical view of psychic
      phenomena are outlined. Furthermore, a previously unpublished letter from Freud
      to Sadger in 1902 is presented and its possible context discussed. I show that
      Sadger probably already began carrying out analyses in 1898 and that, of Freud's
      immediate circle in Vienna, he was either the first or the second doctor to begin
      analytical work. In addition Sadger already made references to Freud in his
      publications in 1897. In summary, Isidor Sadger was probably the only one of
      Freud's disciples for whom the following combination was true: he became
      interested in Freud's approach before 1900, carried out analyses before 1900,
      publicly spoke out for Freud before 1900, became a member of the Wednesday group
      and stayed in Freud's vicinity for a long time (until 1933).

PMID- 21842566
TI  - Fliess versus Weininger, Swoboda and Freud: the plagiarism conflict of 1906
      assessed in the light of the documents.
AB  - Based on sources that have so far partly been neglected, this paper examines the
      accusations of plagiarism that Fliess levelled against Weininger, Swoboda and
      Freud in 1906, trying to determine to what degree they can or cannot be
      justified. In the case of Weininger it seems clear that his theory of bisexuality
      was stimulated by an indirect communication of Freud which harked back to a
      Fliessian idea. But there is no evidence that he had heard anything about the
      specific version of this theory in which Fliess felt plagiarized. In the case of
      Swoboda any reproach of plagiarism was out of place because he explicitly
      utilized ideas (about periodicity) which had already been published. He did,
      however, veil the extent of his dependence on Fliess, while Fliess ignored the
      originality of Swoboda's psychological (rather than biological) approach. The
      fact that Fliess set the two cases in parallel and related them both to an
      indiscretion of Freud, confirms the paranoid pattern of his accusations. The
      paper concludes that the episode is not suitable to use as evidence for a hostile
      paradigm of studies of Freud.

PMID- 21842567
TI  - Brucke's great-grandson's visit to Freud: a contribution to the understanding of
      Freud's relationship to Ernst Brucke.
AB  - Ernst Brucke's great-grandson paid a visit to Freud on 27 September 1932.
      Previously unknown documents relating to this visit, which Freud mentioned in his
      "Shortest Chronicle" ("Kurzeste Chronik"), provide evidence that this was Franz
      Theodor Brucke, 24 years old at the time. During the conversation, there was
      mention of the biography of Ernst Brucke, written in 1928 by his grandson, Ernst
      Theodor, the father of Franz Theodor Brucke, of which Freud had no knowledge.
      After he received a copy of the book, Freud quickly responded with a previously
      unknown letter to Franz Theodor Brucke, in which he emphasized Brucke's "capacity
      for love" and corrected details in the biography, including the cause of the blow
      to Brucke's nose. The relationship of Freud and Brucke will be described in a
      review of known sources and it will be shown that Brucke functioned to a great
      extent and into old age as an ego ideal for Freud. He also represented Freud's
      high standards, while Ernst Fleischl, who is mentioned twice in the letter by
      Freud, epitomizes the danger of failure.

PMID- 21842568
TI  - Ilse Lehiste. 31.01.1922-25.12.2010.

PMID- 21842569
TI  - Freud, the "via regia," and Alexander the Great.
AB  - This article explores the ancient classical background to Freud's use of the
      phrase "via regia" (Royal Road) and Freud's affiliation with Alexander the Great.

PMID- 21842570
TI  - How do macro-level contexts and policies affect the employment chances of
      chronically ill and disabled people? Part I: The impact of recession and
      deindustrialization.
AB  - Low employment rates of chronically ill and disabled people are of serious
      concern. Being out of work increases the risk of poverty and social exclusion,
      which may further damage the health of these groups, exacerbating health
      inequalities. Macro-level policies have a potentially tremendous impact on their
      employment chances, and these influences urgently need to be understood as the
      current economic crisis intensifies. In Part I of this two-part study, the
      authors examine employment trends for people who report a chronic illness or
      disability, by gender and educational level, in Canada, Denmark, Norway, Sweden,
      and the United Kingdom in the context of economic booms and busts and
      deindustrialization. People with the double burden of chronic illness and low
      education have become increasingly marginalized from the labor market.
      Deindustrialization may have played a part in this process. In addition, periods
      of high unemployment have sparked a downward trend in employment for already
      marginalized groups who did not feel the benefits when the economy improved.
      Norway and Sweden have been better able to protect the employment of these groups
      than the United Kingdom and Canada. These contextual differences suggest that
      other macro-level factors, such as active and passive labor market polices, may
      be important, as examined in part II.

PMID- 21842571
TI  - How do macro-level contexts and policies affect the employment chances of
      chronically ill and disabled people? Part II: The impact of active and passive
      labor market policies.
AB  - The authors investigate three hypotheses on the influence of labor market
      deregulation, decommodification, and investment in active labor market policies
      on the employment of chronically ill and disabled people. The study explores the
      interaction between employment, chronic illness, and educational level for men
      and women in Canada, Denmark, Norway, Sweden, and the United Kingdom, countries
      with advanced social welfare systems and universal health care but with varying
      types of active and passive labor market policies. People with chronic illness
      were found to fare better in employment terms in the Nordic countries than in
      Canada or the United Kingdom. Their employment chances also varied by educational
      level and country. The employment impact of having both chronic illness and low
      education was not just additive but synergistic. This amplification was strongest
      for British men and women, Norwegian men, and Danish women. Hypotheses on the
      disincentive effects of tighter employment regulation or more generous welfare
      benefits were not supported. The hypothesis that greater investments in active
      labor market policies may improve the employment of chronically ill people was
      partially supported. Attention must be paid to the differential impact of macro
      level policies on the labor market participation of chronically ill and disabled
      people with low education, a group facing multiple barriers to gaining
      employment.

PMID- 21842572
TI  - Class relations and all-cause mortality: a test of Wright's social class scheme
      using the Barcelona 2000 Health Interview Survey.
AB  - The aim of this study is to test the effects of neo-Marxian social class and
      potential mediators such as labor market position, work organization, material
      deprivation, and health behaviors on all-cause mortality. The authors use
      longitudinal data from the Barcelona 2000 Health Interview Survey (N=7526), with
      follow-up interviews through the municipal census in 2008 (95.97% response rate).
      Using data on relations of property, organizational power, and education, the
      study groups social classes according to Wright's scheme: capitalists, petit
      bourgeoisie, managers, supervisors, and skilled, semi-skilled, and unskilled
      workers. Findings indicate that social class, measured as relations of control
      over productive assets, is an important predictor of mortality among working
      class men but not women. Workers (hazard ratio = 1.60; 95% confidence interval,
      1.10-2.35) but also managers and small employers had a higher risk of death
      compared with capitalists. The extensive use of conventional gradient measures of
      social stratification has neglected sociological measures of social class
      conceptualized as relations of control over productive assets. This concept is
      capable of explaining how social inequalities are generated. To confirm the
      protective effect of the capitalist class position and the "contradictory class
      location hypothesis," additional efforts are needed to properly measure class
      among low-level supervisors, capitalists, managers, and small employers.

PMID- 21842573
TI  - Monitoring social determinants of health inequalities: the impact of unemployment
      among vulnerable groups.
AB  - Surveillance of social determinants of health inequalities is an essential but
      still underdeveloped issue in public health. Existing research has identified
      unemployment as an important social determinant of health inequalities. This
      cross-sectional study investigates the impact of unemployment on mental health
      outcomes among vulnerable groups, using the 2006 Catalonian Health Survey
      (N=8591). The authors estimate the prevalence ratios and differences (excess of
      prevalence) for poor mental health in the unemployed and employed, with 95
      percent confidence intervals. After taking into account the interactions among
      social mechanisms of inequality and related factors, the authors identified seven
      vulnerable groups to monitor. Primary findings indicate that unemployment has a
      greater adverse effect on the mental health of male manual workers, single
      mothers, main-earner women, and manual workers without unemployment benefits for
      both sexes. Findings support the need to devote more research to the surveillance
      of unemployment as a social determinant of health inequalities, to identify
      additional unemployment indicators, and to consider how various social mechanisms
      of inequality interact with each other to produce health inequalities among
      vulnerable groups.

PMID- 21842574
TI  - Preventive control of breast and cervical cancer in immigrant and native women in
      Spain: the role of country of origin and social class.
AB  - The study describes the periodic use of cervical and breast cancer screening by
      women residing in Spain, according to their country of origin, and analyzes
      whether the observed associations are modified by social class. A cross-sectional
      design was used, with the study population consisting of women residing in Spain
      in 2006, ages 25-65 years (N = 10,093) and 40-69 years (N = 6674) in the cervical
      and breast cancer screening groups, respectively. The information source was
      Spain's National Health Survey of 2006. The dependent variables were: undergoing
      periodic cervical cancer screening (every 5 years or less) and breast cancer
      screening (every 2 years or less). The independent variables were: country of
      origin, social class, health care coverage, cohabitation, and age. A descriptive
      analysis was carried out, and robust Poisson regression models were fitted. Women
      from low-income countries underwent fewer periodic screening exams for cervical
      cancer and breast cancer. Independent of country of origin, women from the manual
      classes underwent fewer screening exams than those from the non-manual classes.
      In the 50-69 years age group, it was mainly women from the manual classes from
      low-income countries who underwent fewer periodic mammograms. Having only public
      health care coverage and not cohabiting with a partner were also associated with
      lower prevalences of use.

PMID- 21842575
TI  - The impact of neoliberal "political attack" on health: the case of the "Scottish
      effect".
AB  - The health impact of neoliberal "shock treatment" has been explored in relation
      to the former USSR, but much remains to be done to ascertain its impact
      elsewhere. The authors consider the "Scottish Effect" in health-the unexplained
      excess mortality in Scotland, compared with the rest of Britain, after accounting
      for deprivation. A prevalent but as yet untested view is that this effect is
      linked to the neoliberal "political attack" against the organized working class,
      implemented by the post-1979 U.K. Conservative governments. The article begins to
      develop and test this view in the form of a "political attack hypothesis". It
      shows how the west of Scotland became a particular target for the political
      attack planned by the U.K. Conservative Party prior to its election in 1979;
      outlines how such an attack might affect health; and shows that after 1979 the
      United Kingdom as a whole was exposed to neoliberalism in a way other European
      nations were not and, crucially, that the west of Scotland was more vulnerable to
      its damaging effects than other U.K. regions. The authors conclude that it is now
      appropriate to explore more fully the role of neoliberal political attack in
      creating the "Scottish Effect" in health.

PMID- 21842576
TI  - "Responsibilizing" a healthy Britain: personal debt, employment, and welfare.
AB  - Growing evidence suggests that experiences of financial strain and over
      indebtedness can contribute to problems of physical and mental health. This
      article contends that there is a need to carefully examine recent neoliberally
      informed symbolic and material transformations in the practices and experiences
      of employment, welfare, and subjectivity in order to provide an appropriately
      sophisticated analysis of experiences of debt and mental health. An illusion of
      economic growth has been based on increasing levels of often traumatic personal
      debt and a low-wage labor force compelled into increasingly problematic practices
      of employment. In recent years, a concerted neoliberal assault on subjectivity,
      modes of employment, minimum incomes, and practices of welfare governance has
      effectively constituted new forms of poverty and personal sustenance through
      deregulated sub-prime credit markets. The variable and multifunctional nature of
      personal debt has provided a substrate for neoliberal public policy by
      systematically reinforcing the development of a low-wage labor market and by
      representing a means through which to transfer collective risk into private
      responsibility. This article suggests that traditional ways of knowing and acting
      upon the mental and physical health difficulties associated with problems of debt
      and material deprivation fail to adequately acknowledge the political and
      economic role of personal debt growth.

PMID- 21842577
TI  - Commercial influence and global nongovernmental public action in health and
      pharmaceutical policies.
AB  - Nongovernmental public action has been effective in influencing global agenda
      setting in health and pharmaceutical policies, yet its record in influencing
      solutions to the problems identified has been notably more limited. While trade
      policies have been particularly resistant to change, more substantial changes are
      observable in global health policies and global health governance. However, some
      of the directions of change may not be conducive to the democratic accountability
      of global health governance, to the wise use of public resources, to health
      systems development, or to longer-term access to health care within developing
      countries. The authors argue that observed changes in global health policies can
      be understood as accommodating to corporate concerns and priorities. Furthermore,
      the changing global context and the commercialization of global public action
      itself pose sharp challenges to the exercise of influence by global
      nongovernmental public actors. Nongovernmental organizations not only face a
      major challenge in terms of the imbalance in power and resources between
      themselves and corporate interest groups when seeking to influence policymaking;
      they also face the problem of corporate influence on public action itself.

PMID- 21842578
TI  - Liberalizing the health care market: the new government's ambition for the
      English National Health Service.
AB  - England's National Health Service (NHS) faces the prospect of a radical overhaul
      by the current coalition government, with the aim of improving the quality and
      efficiency of health services. The government has identified the increased use of
      competition between providers as a primary lever to achieve its goals and is
      creating a competitive market comprising state, private, and not-for-profit
      providers. This market will be overseen by an independent economic regulator with
      powers to intervene and shape local markets for health services. While the use of
      market incentives is not wholly novel, if implemented, these new reforms imply a
      rapid expansion of the scope and scale of competitive market forces within the
      NHS. This article examines the government's current proposals for increased use
      of competition and considers its potential impact in the light of the available
      evidence. It argues that despite some research evidence pointing to the
      potentially beneficial effects of competition on quality and efficiency, there
      are also risks of adverse outcomes. Consequently, there is significant
      uncertainty as to whether this policy will deliver the desired objectives.

PMID- 21842579
TI  - The deepening crisis in U.S. health care: a review of data.
AB  - This report presents information on the state of the U.S. health system in 2010.
      It includes data on the uninsured and underinsured and their access to health
      care, on socioeconomic inequality in health care, and on the rising costs of the
      U.S. health system. It also presents information on the role of corporate money
      in health care, focusing on the pharmaceutical industry, Medicare HMOs, and
      corporate-government conflicts of interest. The author includes results from
      public opinion polls on health system reform and recent data on international
      health systems and international system comparisons. The article concludes with
      an update on the U.S. federal health reform legislation.

PMID- 21842580
TI  - Subharmonic contrast microbubble signals for noninvasive pressure estimation
      under static and dynamic flow conditions.
AB  - Our group has proposed the concept of subharmonic aided pressure estimation
      (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the
      noninvasive estimation of hydrostatic blood pressures. An experimental system for
      in vitro SHAPE was constructed based on two single-element transducers assembled
      confocally at a 60 degree angle to each other. Changes in the first, second and
      subharmonic amplitudes of five different ultrasound contrast agents were measured
      in vitro at static hydrostatic pressures from 0-186 mmHg, acoustic pressures from
      0.35-0.60 MPa peak-to-peak and frequencies of 2.5-6.6 MHz. The most sensitive
      agent and optimal parameters for SHAPE were determined using linear regression
      analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI).
      This implementation of SHAPE was then tested under dynamic-flow conditions and
      compared to pressure-catheter measurements. Over the pressure range studied, the
      first and second harmonic amplitudes reduced approximately 2 dB for all contrast
      agents. Over the same pressure range, the subharmonic amplitudes decreased by 9
      14 dB and excellent linear regressions were achieved with the hydrostatic
      pressure variations (r = 0.98, p < 0.001). Optimal sensitivity was achieved at a
      transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid
      (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE
      on a convex transducer with a frequency range from 1.5-4.5 MHz and acoustic
      pressures from 0-3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In
      conclusion, subharmonic contrast signals are a good indicator of hydrostatic
      pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the
      most sensitive for subharmonic pressure estimation. Real-time SHAPE has been
      implemented on a commercial scanner and offers the possibility of allowing
      pressures in the heart and elsewhere to be obtained noninvasively.

PMID- 21842581
TI  - Noninvasive assessment of wall-shear rate and vascular elasticity using combined
      ARFI/SWEI/spectral Doppler imaging system.
AB  - The progression of atherosclerotic disease is a complex process believed to be a
      function of the localized mechanical properties and hemodynamic loading
      associated with the arterial wall. It is hypothesized that measurements of
      cardiovascular stiffness and wall-shear rate (WSR) may provide important
      information regarding vascular remodeling, endothelial function and the growth of
      soft lipid-filled plaques that could help a clinician better predict the
      occurrence of clinical events such as stroke. Two novel ARFI based imaging
      techniques, combined on-axis/off-axis ARFI/Spectral Doppler Imaging (SAD-SWEI)
      and Gated 2D ARFI/Spectral Doppler Imaging (SAD-Gated), were developed to form co
      registered depictions of B-mode echogenicity, ARFI displacements, ARF-excited
      transverse wave velocity estimates and estimates ofwall-shear rate throughout the
      cardiac cycle. Implemented on a commercial ultrasound scanner, the developed
      techniques were evaluated in tissue-mimicking and steady-state flow phantoms and
      compared with conventional techniques, other published study results and
      theoretical values. Initial in vivo feasibility of the method is demonstrated
      with results obtained from scanning the carotid arteries of five healthy
      volunteers. Cyclic variations over the cardiac cycle were observed in on-axis
      displacements, off-axis transverse-wave velocities and wall-shear rates.

PMID- 21842582
TI  - Ultrafast photoacoustic imaging and its application to real-time 3D imaging with
      improved focusing.
AB  - The restricted temporal resolution ofphotoacoustic imaging due to limited frame
      rates often prohibits its applications in areas such as real-time 3D imaging.
      This paper presents an ultrasound/photoacoustic multimodality imaging system that
      provides an ultrafast frame rate and consists of an ultrasound transducer array
      with plane wave excitation and a laser with pulse repetition frequency up to 2000
      Hz. Its application to real-time 3D photoacoustic imaging is demonstrated and a
      synthetic-aperture focusing technique is applied to improve the elevational
      focusing quality of the mechanically-scanned 1D array. A 3D frame rate of 12 Hz
      in a volume covering a 19.2 mm x 19.2 mm scanning surface is demonstrated.

PMID- 21842583
TI  - Progress in ring array transducers for real-time 3D ultrasound guidance of
      cardiac interventional devices.
AB  - As a treatment for aortic stenosis, several companies have recently introduced
      prosthetic heart valves designed to be deployed through a catheter using an
      intravenous or transapical approach. This procedure can either take the place of
      open heart surgery with some ofthe devices or delay it with others. Real-time 3D
      ultrasound could enable continuous monitoring of these structures before, during
      and after deployment. We have developed a 2D ring array integrated with a 30
      French catheter that is used for transapical prosthetic heart valve implantation.
      The transducer array was built using three 46 cm long flex circuits from
      MicroConnex (Snoqualmie, WA) which terminate in an interconnect that plugs
      directly into our system cable; thus, no cable soldering is required. This
      transducer consists of 210 elements at 0.157 mm interelement spacing and operates
      at 5 MHz. Average measured element bandwidth was 26% and average round-trip 50
      ohm insertion loss was -58.1 dB after correcting for diffractive losses. The
      transducer was wrapped around the 1 cm diameter lumen of a heart-valve deployment
      catheter. Prosthetic heart valve images were obtained in water-tank studies.

PMID- 21842584
TI  - 7.5 MHz dual-layer transducer array for 3-D rectilinear imaging.
AB  - The difficulties associated with fabrication and interconnection have limited the
      development of 2-D ultrasound transducer arrays with a large number ofelements
      (>5000). In previous work, we described a 5 MHz center frequency PZT-P[VDF-TrFE]
      dual-layer transducer that used two perpendicular 1-D arrays for 3-D rectilinear
      imaging. This design substantially reduces the channel count as well as
      fabrication complexity, which makes 3-D imaging more realizable. Higher
      frequencies (>5 MHz) are more commonly used in clinical applications or imaging
      targets near transducers, such as the breast, carotid and musculoskeletal tissue.
      In this paper, we present a 7.5 MHz dual-layer transducer array for 3-D
      rectilinear imaging. A modified acoustic stack model was designed and fabricated.
      PZT elements were sub-diced to eliminate lateral coupling. This sub-dicing
      process made the PZT into a 2-2 composite material, which could help improve
      transducer sensitivity and bandwidth. Full synthetic-aperture 3-D data sets were
      acquired by interfacing the transducer with a Verasonics data-acquisition system
      (VDAS). Offline 3-D beamforming was then performed to obtain volumes of a
      multiwire phantom and a cyst phantom. The generalized coherence factor (GCF) was
      applied to improve the contrast of cyst images. The measured -6 dB fractional
      bandwidth of the transducer was 71% with a center frequency of 7.5 MHz. The
      measured lateral beamwidths were 0.521 mm and 0.482 mm in azimuth and elevation,
      respectively, compared with a simulated beamwidth of 0.43 mm.

PMID- 21842585
TI  - Thirty years of Acta Myologica.

PMID- 21842586
TI  - The microglial-motoneuron dialogue in ALS.
AB  - Neuroinflammation is a pathological hallmark of neurodegenerative diseases
      including amyotrophic lateral sclerosis (ALS), and is characterized by activated
      microglia at sites of neuronal injury. In ALS, neurons do not die alone; neuronal
      injury is noncell-autonomous and depends upon a well-orchestrated dialogue
      between motor neurons and microglia. Evidence from transgenic models expressing
      mutant superoxide dismutase 1 (SOD) suggests that the dialogue between motor
      neurons and microglia initially protects motor neurons. However, with increasing
      stress and injury within motor neurons, induced by the presence of misfolded
      proteins such as mSOD1, mitochondrial function and axoplasmic flow are impaired
      and endoplasmic reticulum stress is induced; misfolded proteins themselves or
      alternate signals are released from motor neurons and activate microglia.
      Activated microglia, in turn, switch from anti-inflammatory and neuroprotective
      to proinflammatory and neurotoxic. Neurotoxic signaling from motor neurons
      promotes microglial release of reactive oxygen species and pro-inflammatory
      cytokines further enhancing motor neuron stress and cell injury and initiating a
      self-propagating cycle of motor neuron injury and cell death. A greater
      understanding of how to restore the imbalance between neuroprotection and
      cytotoxicity will depend upon a greater understanding of the motor neuron
      microglial dialogue.

PMID- 21842587
TI  - Cardiological manifestations of mitochondrial respiratory chain disorders.
AB  - Mitochondrial Respiratory Chain Disorders (MRCD) are a heterogeneous group of
      disorders that share the involvement of the cellular bioenergetic machinery due
      to molecular defects affecting the mitochondrial oxidative phosphorylation system
      (OXPHOS). Clinically, they usually involve multiple tissues although they tend to
      mainly affect nervous system and skeletal muscle. Cardiological manifestations
      are frequent and include hypertrophic or dilated cardiomyopathies and heart
      conduction defects, being part of adult or infantile multisystemic mitochondrial
      disorders or, less frequently, presenting as isolated clinical condition. The aim
      of this review is to update the cardiological manifestations in both adult and
      infantile mitochondrial disorders going briefly over mitochondrial genetics.
      Cardiac involvement is a common feature associated with early and late onset
      forms of MRCD. In particular cases, these conditions should be considered into
      the diagnostic algorithm of idiopathic cardiomyopathies. Physicians strictly
      related with this disorders need to be aware of heart complications and therefore
      periodical cardiological examinations should be performed in such patients.
      Finally, therapeutic strategies are suggested to treat cardiac disorders in MRCD

PMID- 21842588
TI  - Activation of NF-kappaB pathway in Duchenne muscular dystrophy: relation to age.
AB  - Muscle degeneration in Duchenne muscular dystrophy (DMD) is exacerbated by
      increased oxidative stress and the endogenous inflammatory response, with a key
      role played by nuclear factor kappa-B (NF-kappaB) and other related factors such
      as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. However the time
      course of expression of these molecules and the relation with the amount of
      necrosis and regeneration have never been investigated. The expression of NF
      kappaB, the cytokines TNF-alpha and IL-6 and the antioxidant enzyme glutathione
      peroxidase (GPx) was studied in muscle samples from 14 patients with DMD aged
      between 2 and 9 years. Moreover a quantitative morphological evaluation was
      performed to evaluate necrotic and regenerative areas. The highest percentage of
      necrosis was revealed within 4 years of age, with a significant negative
      correlation with age (p < 0.003), which paralleled to a significant decrement of
      regenerating area (p < 0.0004). We reported the novel observation that the number
      of NF-kappaB positive fibers and the NF-kappaB DNA-binding activity, revealed by
      EMSA, are high at two years of life and significantly decline with age (p <
      0.0005 and p < 0.0001). The expression of TNF-alpha, IL-6 and GPx was upregulated
      in DMD muscles compared to controls and significantly increased with age on real
      time PCR analysis (p < 0.0002; p < 0.0005; p < 0.03 respectively) and ELISA (p <
      0.002; p < 0.02; p < 0.0001 respectively). Since anti-inflammatory and anti
      oxidant drugs are nowadays being translated to clinical studies in DMD, the
      reported insights on these therapeutic targets appear relevant. Further studies
      on the interactions among these pathways in different DMD phases and on the
      response of these cascades to treatments currently under investigation are needed
      to better elucidate their relevance as therapeutic targets.

PMID- 21842589
TI  - Mesoangioblasts of inclusion-body myositis: a twofold tool to study pathogenic
      mechanisms and enhance defective muscle regeneration.
AB  - Mesoangioblasts are a class of adult stem cells of mesoderm origin, potentially
      useful for the treatment of primitive myopathies of different etiology. Extensive
      in vitro and in vivo studies in animal models of muscular dystrophy have
      demonstrated the ability of mesoangioblast to repair skeletal muscle when
      injected intra-arterially. In a previous work we demonstrated that
      mesoangioblasts obtained from diagnostic muscle biopsies of IBM patients display
      a defective differentiation down skeletal muscle and this block can be corrected
      in vitro by transient MyoD transfection. We are currently investigating different
      pathways involved in mesoangioblasts skeletal muscle differentiation and
      exploring alternative stimulatory approaches not requiring extensive cell
      manipulation. This will allow to obtain safe, easy and efficient molecular or
      pharmacological modulation of pro-myogenic pathways in IBM mesoangioblasts. It is
      of crucial importance to identify factors (ie. cytokines, growth factors)
      produced by muscle or inflammatory cells and released in the surrounding milieu
      that are able to regulate the differentiation ability of IBM mesoangioblasts. To
      promote myogenic differentiation of endogenous mesoangioblasts in IBM muscle, the
      modulation of such target molecules selectively dysregulated would be a more
      handy approach to enhance muscle regeneration compared to transplantation
      techniques. Studies on the biological characteristics of IBM mesoangioblasts with
      their aberrant differentiation behavior, the signaling pathways possibly involved
      in their differentiation block and the possible strategies to overcome it in
      vivo, might provide new insights to better understand the etiopathogenesis of
      this crippling disorder and to identify molecular targets susceptible of
      therapeutic modulation.

PMID- 21842590
TI  - HIV-related neuromuscular diseases: nemaline myopathy, amyotrophic lateral
      sclerosis and bibrachial amyotrophic diplegia.
AB  - The human immunodeficiency virus (HIV) causes diverse disorders of the brain,
      spinal cord and peripheral nerves. Rarely, polymyositis and myoglobinuria are
      seen. Two other neuromuscular syndromes in people with HIV antibodies are
      nemaline myopathy and bibrachial amyotrophic diplegia, a form of motor neuron
      disease. The associations between these diseases and the possibility that HIV
      infection could be a risk factor for either amyotrophic lateral sclerosis (ALS)
      itself or other motor neuron diseases are investigated.

PMID- 21842591
TI  - Continuous muscle activity, Morvan's syndrome and limbic encephalitis: ionic or
      non ionic disorders?
AB  - The early pathophysiologic study showed increasing evidence that autoimmunity is
      implicated in the pathogenesis of neuromyotonia. Antibodies to voltage gated
      potassium channel were detected in the serum of patients who had peripheral
      nerves hyperexcitability and also Morvan's disease or limbic encephalitis. These
      discoveries offered new approaches to treatments. Recently, antibodies previously
      attributed to VGKC recognise 2 surface antigens LGI1 and CASPR2 into the VGKC
      complex. Finally, VGKC antibodies are directed to 2 proteins the first one is a
      key hippocampic protein containing pre and post synaptic proteins. The second one
      CASPR2 is an hippocampic and paranodal protein. There clinical significance is
      different: hyperexcitability, limbic encephalitis without thymoma for LGI1,
      hyperexcitability, Morvan limbic encephalitis and frequent thymoma for CASPR2. In
      conclusion, the term NMT--LE--VGKC should be changed to NMT--LE with LGII and
      CASPR2 antibodies and classified as auto immune synaptic disorders. Mutations in
      genes encoding both these proteins are found in hereditary epilepsy and other
      syndromes. Various potassium channelopathies are closely linked to Morvan's
      syndromes. A new classification of antibodies will be necessary.

PMID- 21842592
TI  - Sporadic-inclusion body myositis (s-IBM) is not so prevalent in Istanbul/Turkey:
      a muscle biopsy based survey.
AB  - In a muscle biopsy based study, only 9 out of 5450 biopsy samples, received from
      all parts of greater Istanbul area, had typical clinical and most suggestive
      light microscopic sporadic-inclusion body myositis (s-IBM) findings. Two other
      patients with and ten further patients without characteristic light microscopic
      findings had referring diagnosis of s-IBM. As the general and the age-adjusted
      populations of Istanbul in 2010 were 13.255.685 and 2.347.300 respectively, the
      calculated corresponding 'estimated prevalences' of most suggestive s-IBM in the
      Istanbul area were 0.679 X 10(-6) and 3.834 X 10(-6). Since Istanbul receives
      heavy migration from all regions of Turkey and ours is the only muscle pathology
      laboratory in Istanbul, projection of these figures to the Turkish population was
      considered to be reasonable and an estimate of the prevalence of s-IBM in Turkey
      was obtained. The calculated 'estimated prevalence' of s-IBM in Turkey is lower
      than the previously reported rates from other countries. The wide variation in
      the prevalence rates of s-IBM may reflect different genetic, immunogenetic or
      environmental factors in different populations.

PMID- 21842593
TI  - A correlative study of quantitative EMG and biopsy findings in 31 patients with
      myopathies.
AB  - A direct correlation of QEMG with muscle biopsy findings might help delineate the
      sensitivity of QEMG in identifying muscle pathology as well as provide
      information on electrophysiological-histological correlations. In a study of 31
      patients with a variety of myopathies we found that the sensitivity of QEMG was
      between 24 to 69% depending of the specific method of signal analysis. The
      positive predictive value of abnormal QEMG was more than 90% while its negative
      predictive value was only about 20%. Amplitude outlier analysis was superior
      especially in minimally weak muscles (MRC > 4) and was particularly sensitive at
      detecting increased variability in fiber size and more subtle myopathic changes.

PMID- 21842594
TI  - Desmin A213V substitution represents a rare polymorphism but not a mutation and
      is more prevalent in patients with heart dilation of various origins.
AB  - Several desmin mutations have been described in patients with cardiomyopathies
      and distal myopathies. Among them, A213V substitution has been associated with
      three completely different clinical phenotypes: restrictive cardiomyopathy,
      dilated cardiomyopathy and isolated distal myopathy. However, the identification
      of this substitution also in control subjects has highlighted the question if the
      A213V shift represents a conditional mutation, giving rise to cardiomyopathy only
      in the presence of other predisposing factors. The aim of the present work was to
      study the potential role of this substitution in predisposing to heart dilation.
      Methods and results. We screened 108 patients with heart dilation due to ischemic
      heart disease, alcoholic cardiomyopathy or viral myocarditis, and 300 healthy
      controls for the presence of A213V substitution by direct sequencing and
      confirmed the results by site-specific restriction. In the control group A213V
      substitution was identified in 3 out of 300 patients, representing a rare
      polymorphism with a frequency of approximately 1%, which corresponds to the
      earlier reported frequency. In the study group A213V substitution was found in 5
      out of 108 cases, corresponding to approximately 4.6% (p < 0.035). Therefore we
      conclude that A213V desmin substitution represents a conditional mutation, i.e. a
      rare polymorphism that plays a role as a predisposing factor resulting in
      maladaptive heart remodelling in the presence of other pathological factors.

PMID- 21842595
TI  - Right ventricular obstructive hypertrophic cardiomyopathy in primary myo
      adenylate deaminase deficiency.
AB  - MyoAdenylate Deaminase Deficiency (MADD) is a relatively common metabolic
      disorder of the skeletal muscle. Patients with MADD usually show an impaired
      bioenergetic production and a clinical spectrum with either exercise-induced
      muscle pain, fatigue and/or rhabdomyolysis. Left ventricular hypertrophy as well
      as other types of cardiac involvement have been reported in patients with primary
      MADD. We describe herein a case of a 61-year-old woman with biochemical and
      genetic evidence of Myo-Adenylate Deaminase deficiency, in whom we found a right
      ventricular hypertrophic cardiomyopathy leading to severe outflow tract dynamic
      obstruction.

PMID- 21842596
TI  - [Histological atlas of immunoglobulin (IgA) nephropathy].

PMID- 21842597
TI  - [Membranous nephropathy. Preface].

PMID- 21842598
TI  - [Roles of igG4 subclass and cellular immunity in idiopathic membranous
      nephropathy].

PMID- 21842599
TI  - [Pathogenic mechanism of membranous glomerulonephritis obtained from Heymann
      nephritis and human membranous glomerulonephritis].

PMID- 21842600
TI  - [Epidemiology of membranous nephropathy in Japan].

PMID- 21842601
TI  - [Pathology of membranous nephropathy].

PMID- 21842602
TI  - [Membranous nephropathy: up to date].

PMID- 21842603
TI  - [Secondary membranous nephropathy].

PMID- 21842604
TI  - [Secondary membranous nephropathy: The topics of membranous lupus nephritis].

PMID- 21842605
TI  - [Treatment and prognosis of idiopathic membranous nephropathy in guidelines for
      nephrotic syndrome].

PMID- 21842606
TI  - [Successful rituximab therapy for MALT lymphoma complicating cryoglobulinemic
      glomerulonephritis].
AB  - We report a case of nephrotic syndrome associated with MALT lymphoma. The patient
      was a 66-year-old woman who had a 21-year history of MALT lymphoma. She was
      admitted to our hospital for the evaluation of systemic edema and purpura during
      two months. Urinary protein excretion was quantified at 3.3 g/24h. Serum
      creatinine was elevated to 1.63 mg/dL. An immunoserological investigation showed
      the presence of IgM-kappa type monoclonal cryoglobulin accompanied by a decreased
      serum complement level. HCV infection was negative. A renal biopsy specimen
      revealed membranoproliferative glomerulonephritis (MPGN) with cryoglobulin
      deposition and focal atypical lymphoid cells infiltration in the renal
      interstitium. Immunoperoxidase staining of the atypical lymphoid cell population
      was positive for CD20 and CD79. Combined therapy with prednisolone, plasma
      exchange and rituximab was commenced. Her proteinuria disappeared and renal
      function improved after rituximab therapy. In our case, nephrotic syndrome due to
      cryoglobulinemic glomerulonephritis was successfully treated mainly by rituximab.

PMID- 21842607
TI  - [Case of fanconi syndrome positive for anti-M2 antibodies revealed by severe
      hypokalemia and multiple bone fracture].
AB  - A 38-year-old female developed pain in the right leg in 2006. In 2007, the
      diagnosis of femoral head necrosis was made based on MR images, and femoral head
      prosthetic replacement was performed. In April 2009, she visited a local hospital
      for low back pain, and was referred to our department due to electrolyte
      abnormalities on hemanalysis. Since marked hypokalemia (K=2.5 mEq/L),
      hypophosphatemia, hyperchloric metabolic acidosis, proteinuria, and urinary blood
      sugar suggested Fanconi syndrome, she was admitted for close examination. Bone
      survey showed a marked decrease in the amount of bone particularly in the four
      limbs and fracture at the proximal 1/3 of the left ulnar bone. In the lumbar
      spine, scoliosis and vertebral deformity were observed. Since impaired P re
      absorption and unselected aminoaciduria and osteomalacia were also present, the
      diagnosis of Fanconi syndrome was made. On admission, ventricular tachycardia
      developed due to hypokalemia, requiring immediate electrolyte correction. For
      differentiation from acquired Fanconi syndrome, various examinations were
      performed. No apparent cause was found except for the positive antimitochondrial
      antibody-M2 (anti-M2). In this case, no data suggested liver dysfunction, and
      subsequent liver biopsy also showed no significant pathological findings pointing
      to PBC. We encountered a patient with Fanconi syndrome positive for anti-M2. This
      case may attract interest, particularly in the mechanism of nephropathy due to
      anti-M2, and therefore, this case is reported with a literature review.

PMID- 21842608
TI  - [Case of distal renal tubular acidosis complicated with renal diabetes insipidus,
      showing aggravation of symptoms with occurrence of diabetes mellitus].
AB  - We report herein a 27-year-old male case of inherited distal renal tubular
      acidosis complicated with renal diabetes insipidus, the symptoms of which were
      aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he
      was diagnosed as having inherited distal renal tubular acidosis and thereafter
      supplementation of both potassium and alkali was started to treat his hypokalemia
      and metabolic acidosis. At the age of 4 years, calcification of the bilateral
      renal medulla was detected by computed tomography. Subsequently his urinary
      volume gradually increased and polyuria of approximately 4 L/day persisted. At
      the age of 27 years, he became fond of sugar-sweetened drinks and also often
      forgot to take the medicine. He was admitted to our hospital due to polyuria of
      more than 10 L day, muscle weakness and gait disturbance. Laboratory tests
      disclosed worsening of both hypokalemia and metabolic acidosis in addition to
      severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and
      cessation of medications can induce osmotic diuresis and aggravate hypokalemia
      and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced
      damage of his urinary concentration ability and enhancement of the renin
      angiotensin system occurred and thereby possibly worsened his hypokalemia and
      metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis
      might have exacerbated hypokalemia further, dehydration and hypokalemia were
      treated first. Following intensive treatment, these abnormalities were improved,
      but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and
      deficit of renal responses to antidiuretic hormone suggested that the polyuria
      was attributable to the preexisting renal diabetes insipidus possibly caused by
      bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti
      inflammatory drugs were not effective for the treatment of diabetes insipidus in
      the present case.

PMID- 21842609
TI  - Nurses' failure to report changes not material to death claim. MacDonald v.
      Harris Methodist HEB Hospital, 02-10-00267-CV TXCA2 (7/7/2011)-TX.

PMID- 21842610
TI  - RN administered 125 mg of benadryl to two-year-old. Case on point: K. D. v.
      Adrianne Chambers, RN, 49A04-1010-CT-636 (7/13/2011)-IN.

PMID- 21842611
TI  - NY: Asymptomatic pt. died from heart attack: judgment for nurse and drs.
      affirmed. Makinen v. Torelli, 2011-31882 NYMISC (7/7/2011)-NY.

PMID- 21842612
TI  - First responders failed to meet standard of care - pt. died. Case on point: King
      v. St. Barnabas Hospital, 2011-05641 NYAPP1 (6/30/2011)-NY.

PMID- 21842613
TI  - Randomized controlled trials in schizophrenia: opportunities, limitations, and
      trial design alternatives.
AB  - State-of-the art clinical trial design and methodology are enormously important
      for the advancement of the field. In contrast, the critical relevance of trial
      conduct and implementation have only more recently been the focus of discussion
      and research. Although randomized controlled trials are generally considered the
      gold standard for the assessment of pharmacologic and nonpharmacologic
      interventions in medicine, trials are vulnerable to complications and influences
      that can seriously compromise their success. Like interventions, trial design and
      conduct are also contextual. They need to be individualized and adapted to a
      number of relevant variables, such as setting, population, illness phase,
      interventions, patient and rater expectations and biases, and the overall aims of
      the investigation. While this means that there is no unified approach possible,
      certain general principles and guidelines require careful consideration.
      Knowledge of basic solutions and alternatives, and the recognition of the complex
      challenges that need to be addressed proactively can help to minimize unwanted
      outcomes, including trial failure and uninformative or falsely negative outcomes.
      Moreover, novel design alternatives need to be explored that target sample
      enrichment according to the study question and enhancement of precision in the
      measurement of relevant outcomes. We propose two novel design strategies that
      take advantage of the recently validated early antipsychotic response paradigm
      (that has also been observed with antidepressants and mood stabilizers). In the
      "early responder randomized discontinuation design" all patients are assigned to
      the active drug, and only those who had at least a minimal response at 2 weeks
      are enrolled in a double-blind, placebo-controlled discontinuation trial,
      enriching the placebo controlled trial portion with true drug responders. In the
      mirror image "early nonresponder randomized dose increase or augmentation
      design," early nonresponders at 2 weeks are assigned to staying on the medication
      or going either to a higher dose or an augmentation agent. It is hoped that
      through increased attention to the issues raised in this article and further
      refinement of trial methodology and conduct, the field will make much needed
      additional progress in the prevention and treatment of schizophrenia.

PMID- 21842614
TI  - Ethical issues in naturalistic versus controlled trials.
AB  - Ethical core issues in research with human subjects are related to informed
      consent and risk-benefit assessment. This is valid for all types of studies.
      However, there has been much greater focus of ethical considerations on
      controlled clinical trials than on naturalistic trials, probably because the
      former are interventional in nature and may have unknown and perhaps severe
      somatic risks, whereas naturalistic studies seem not to intervene but only to
      observe, and therefore are assumed to have fewer or almost no risks. However,
      there are also ethical implications in naturalistic trials, although their weight
      is differently accentuated, more with potential, more with potential
      psychological burdens of the observational procedures and more with potential
      physical risks in interventional trials. This will be elaborated with examples of
      placebo-controlled trials and of incidental findings in screenings, of marketing
      influences on observational studies, and of psychological burdens by survey
      interviews. The ethical implications will be analyzed within a more general
      framework. Finally, recommendations will be offered.

PMID- 21842615
TI  - Assessing the benefit: risk ratio of a drug--randomized and naturalistic
      evidence.
AB  - Randomized evidence from clinical trials and naturalistic evidence collected from
      pharmacoepidemiology and pharmacovigilance activities both contribute to the
      initial and continuous assessment of the benefits and risks of a drug, ie, the
      balance between therapeutic efficacy and safety risks. Benefit-risk assessment
      (BRA) mainly relies on a qualitative assessment of quantitative data. Current
      attempts to quantify BRA are reviewed and discussed, along with the expectations
      of regulatory authorities such as the Food and Drug Administration and the
      European Medicines Agency. No method provides a fully satisfactory solution
      regarding BRA, because it is difficult to reduce its multidimensional aspect to
      simple metrics, in a context where other therapeutic alternatives play a role.
      Consistency and transparency are key in this assessment, which is performed
      throughout the whole drug life cycle. BRA is mainly based on randomized clinical
      studies during clinical development, and it is continued and consolidated by
      naturalistic data once the drug is on the market.

PMID- 21842616
TI  - Evaluation of psychiatric interventions in an observational study: issues in
      design and analysis.
AB  - Characteristics of randomized controlled clinical trials (RCTs) and observational
      studies of psychiatric intervention effectiveness are contrasted. Randomization
      drives treatment assignment in an RCT, whereas clinician and patient selection
      determine treatment in an observational study. Strengths and weaknesses of
      randomized and observational designs are considered. The propensity adjustment, a
      statistical approach that allows for intervention evaluation in a nonrandomized
      observational study, is described here. The plausibility of propensity adjustment
      assumptions must be carefully evaluated. This data analytic strategy is
      illustrated with the longitudinal observational data from the National Institute
      of Mental Health Collaborative Depression Study. Evaluations presented here
      examine acute and maintenance antidepressant effectiveness and demonstrate
      effectiveness of the higher categorical doses.

PMID- 21842617
TI  - Effectiveness studies: advantages and disadvantages.
AB  - In recent years, so-called "effectiveness studies," also called "real-world
      studies" or "pragmatic trials," have gained increasing importance in the context
      of evidence-based medicine. These studies follow less restrictive methodological
      standards than phase III studies in terms of patient selection, comedication, and
      other design issues, and their results should therefore be better generalizable
      than those of phase III trials. Effectiveness studies, like other types of phase
      IV studies, can therefore contribute to knowledge about medications and supply
      relevant information in addition to that gained from phase III trials. However,
      the less restrictive design and inherent methodological problems of phase IV
      studies have to be carefully considered. For example, the greater variance caused
      by the different kinds of confounders as well as problematic design issues, such
      as insensitive primary outcome criteria, unblinded treatment conditions,
      inclusion of chronic refractory patients, etc, can lead to wrong conclusions. Due
      to these methodological problems, effectiveness studies are on a principally
      lower level of evidence, adding only a complementary view to the results of phase
      III trials without falsifying their results.

PMID- 21842618
TI  - Pragmatic vs explanatory trials: the pragmascope tool to help measure differences
      in protocols of mental health randomized controlled trials.
AB  - In the pragmatic-explanatory continuum, a randomized controlled trial (RCT) can
      at one extreme investigate whether a treatment could work in ideal circumstances
      (explanatory), or at the other extreme, whether it would work in everyday
      practice (pragmatic). How explanatory or pragmatic a study is can have
      implications for clinicians, policy makers, patients, researchers, funding
      bodies, and the public. There is an increasing need for studies to be open and
      pragmatic; however, explanatory trials are also needed. The previously developed
      Pragmatic-explanatory continuum indicator summary (PRECIS) was adapted into the
      Pragmascope tool to assist mental health researchers in designing RCTs, taking
      the pragmatic-explanatory continuum into account. Ten mental health trial
      protocols were randomly chosen and scored using the tool by three independent
      raters. Their results were compared for consistency and the tool was found to be
      reliable and practical. This preliminary work suggests that evaluating different
      domains of an RCT at the protocol level is useful, and suggests that using the
      Pragmascope tool presented here might be a practical way of doing this.

PMID- 21842619
TI  - A pragmatic view on pragmatic trials.
AB  - Clinical trials have been the main tool used by the health sciences community to
      test and evaluate interventions, Trials can fall into two broad categories:
      pragmatic and explanatory. Pragmatic trials are designed to evaluate the
      effectiveness of interventions in real-life routine practice conditions, whereas
      explanatory trials aim to test whether an intervention works under optimal
      situations. Pragmatic trials produce results that can be generalized and applied
      in routine practice settings. Since most results from exploratory trials fail to
      be broadly generalizable, the "pragmatic design" has gained momentum. This review
      describes the concept of pragmatism, and explains in particular that there is a
      continuum between pragmatic and explanatory trials, rather than a dichotomy.
      Special focus is put on the limitations of the pragmatic trials, while
      recognizing the importance for and impact of this design on medical practice.

PMID- 21842620
TI  - Biomarkers in development of psychotropic drugs.
AB  - Biomarkers have been receiving increasing attention, especially in the field of
      psychiatry In contrast to the availability of potent therapeutic tools including
      pharmacotherapy, psychotherapy, and biological therapies, unmet needs remain in
      terms of onset of action, stability of response, and further improvement of the
      clinical course. Biomarkers are objectively measured characteristics which serve
      as indicators of the causes of illnesses, their clinical course, and modification
      by treatment. There exist a variety of markers: laboratory markers which comprise
      the determination of genetic and epigenetic markers, neurotransmitters, hormones,
      cytokines, neuropeptides, enzymes, and others as single measures;
      electrophysiological markers which usually comprise electroencephalography (EEG)
      measures, and in particular sleep EEG and evoked potentials, magnetic
      encephalography, electrocardiogram, facial electromyography, skin conductance,
      and others; brain imaging techniques such as cranial computed tomography,
      magnetic resonance imaging, functional MRI, magnetic resonance spectroscopy,
      positron emission tomography, and single photon emission computed tomography; and
      behavioral approaches such as cue exposure and challenge tests which can be used
      to induce especially emotional processes in anxiety and depression. Examples for
      each of these domains are provided in this review. With a view to developing more
      individually tailored therapeutic strategies, the characterization of patients
      and the courses of different types of treatment will become even more important
      in the future.

PMID- 21842621
TI  - Using a sharp instrument to parse apart strategy and consistency: an evaluation
      of PPT and its assumptions.
AB  - Potential Performance Theory (PPT) is a general theory for parsing observed
      performance into the underlying strategy and the consistency with which it is
      used. Although empirical research has supported that PPT is useful, it is
      desirable to have more information about the bias and standard errors of PPT
      findings. It also is beneficial to know the effects of violations of PPT
      assumptions. The authors present computer simulations that evaluate bias and
      standard errors at varying levels of strategy, consistency, and number of trials
      per participant. The simulations show that, when the assumptions are true, there
      is very little bias and the standard errors are low when there are moderate or
      large numbers of trials per participant (e.g., N=50 or N=100). But when the
      independence assumption is violated, PPT provides biased findings, although the
      bias is quite small unless the violations are large.

PMID- 21842622
TI  - That community becomes you? An examination of community differences in self
      objectification and related variables.
AB  - The authors surveyed women from 2 communities: Anchorage, Alaska (N =51), an
      urban area, and Haines, Alaska (N=41), an isolated rural community. Participants
      from Haines scored lower on measures of self-objectification, internalization of
      sociocultural attitudes toward appearance, participation in beauty enhancement
      behaviors, and perceived normative beauty enhancement behaviors. Women from
      Haines also engaged in more empowering exercise (i.e., yoga and outdoor
      exercise). Internalization of sociocultural attitudes toward appearance mediated
      the relation between perceived normative beauty enhancement behaviors and self
      objectification for women living in both communities. The current study suggests
      that communities may present opportunities to engage in activities that influence
      one's predisposition to self-objectify. The nonexperimental nature of this study,
      however, prevents the definitive establishment of the direction of causality
      between variables.

PMID- 21842623
TI  - An investigation of the accuracy of standardized path coefficients.
AB  - Given the popular and ever-increasing use of path analytic research paradigms in
      the social sciences, it is desirable to conduct an investigation into the
      accuracy of the standardized path coefficients that are often the end-product of
      these paradigms. In pursuit of this goal, population parameters were preset
      concerning the correlations between all of the variables and their reliability
      coefficients. Based on these parameters, thousands of experiments were generated
      with varying numbers of cases (n). For each experiment, at each level of n,
      standard path analyses were conducted, and standardized path coefficients were
      obtained. These standardized path coefficients were then compared against the
      population path coefficients on which the simulations were based to determine
      their accuracy. The findings indicate mixed evidence for the accuracy of path
      analysis research paradigms.

PMID- 21842624
TI  - Object naming in dyslexic children: more than a phonological deficit.
AB  - In the present study, the authors investigate how some visual factors related to
      early stages of visual-object naming modulate naming performance in dyslexia. The
      performance of dyslexic children was compared with 2 control groups-normal
      readers matched for age and normal readers matched for reading level-while
      performing a discrete naming task in which color and dimensionality of the
      visually presented objects were manipulated. The results showed that 2
      dimensional naming performance improved for color representations in control
      readers but not in dyslexics. In contrast to control readers, dyslexics were also
      insensitive to the stimulus's dimensionality. These findings are unlikely to be
      explained by a phonological processing problem related to phonological access or
      retrieval but suggest that dyslexics have a lower capacity for coding and
      decoding visual surface features of 2-dimensional representations or problems
      with the integration of visual information stored in long-term memory.

PMID- 21842625
TI  - It's a just world no matter which way you look at it.
AB  - According to the confluence theory (D. Trafimow, 2009), there is a general
      tendency of associated mental elements to become compatible with each other. It
      is possible to derive a reversibility principle from this theory; effects that
      have been shown to go in 1 direction also can be shown to go in the other
      direction. Two experiments applied these ideas to just-world phenomena. In
      Experiment 1, the authors replicated traditional just-world effects but also
      demonstrated that they occur in the reverse direction. In Experiment 2, the
      authors extend the notion of compatibility by showing that the value participants
      assigned to luck is influenced by the assumed goodness or badness of the person
      involved. The authors also obtained a "contagion" effect whereby a person
      associated with the target person was tainted by the target person's goodness or
      badness.

PMID- 21842626
TI  - Getting ready for 5010.

PMID- 21842628
TI  - Outsourcing ambulatory billing and collections.

PMID- 21842627
TI  - Reform and consumer-directed health care can benefit your revenue cycle.

PMID- 21842629
TI  - Front-desk operations: disastrous or dynamic?

PMID- 21842630
TI  - Coding procedures involving the knee.

PMID- 21842631
TI  - [Review on biosynthesis of podophyllotoxin].
AB  - Podophyllotoxin (PTOX) is an extremely important plant-derived natural product,
      of which derivatives, like etoposide and teniposide, have been widely applied in
      therapies for cancers and venereal wart. A durable, intense plant extraction of
      podophyllotoxin posed a severe pressure on wild resources; researchers
      consequently sought to explore new sources, like cultivation, plant cell or organ
      culture, and chemical synthesis. Understanding biosynthesis of PTOX is one of the
      basic necessary steps for standard cultivation of medicinal plants and metabolite
      engineering. An important progress has been made in this field during the last
      two decades, particularly in the last ten years. Although a number of reviews
      concerning the related topic have existed, we specifically deal with biosynthesis
      of podophyllotoxin with an emphasis on the literatures of the past decade,
      highlighting characterization of genes encoding synthetic enzymes and down-stream
      metabolism of PTOX. The present review focuses on several key biosynthesis
      processes, important metabolites, function of related enzymes, and
      characterization of cDNA encoding the enzymes. Finally, the author proposed a
      hypothetical biosynthetic scheme of podophyllotoxin and perspectives.

PMID- 21842632
TI  - [Research progress of chromanone derivatives from Calophyllum].
AB  - Calophyllum plants have great pharmaceutical value. Some species of this genus
      are used in folk medicine to treat and cure diseases, such as toothache,
      rheumatism, diarrhea, chronic ulcers, skin infections, and wounds. The genus is
      known to be rich in chromanone derivatives, and some of these compounds have
      antiviral, antifungal, antibacterial, cytotoxic, and other activities. In order
      to come to a more complete understanding of chromanone derivatives and gain new
      bioactive constituents from Calophyllum, chemical structures, pharmacological
      activities, and biogenesis of chromanone derivatives from Calophyllum have been
      discussed in this review.

PMID- 21842633
TI  - [Mechanisms and effects of chinese herbal medicine delaying progression of
      chronic renal failure].
AB  - In this review,firstly,it has been discussed the mechanisms of Chinese herbal
      medicine ameliorating glomerulosclerosis and renal interstitial fibrosis during
      the progression of chronic renal failure (CRF) by improving glomerular
      hemodynamics turbulence, podocyte injury, transforming growth factor (TGF)-beta
      over-expression, hyperlipidemia, macrophage infiltration, tubular epithelial
      myofibroblast transdifferentiation, and nephrotoxicity of proteinuria.
      Secondly,it has been reported the clinical effects of Chinese herbal medicine
      improving renal function and some clinical complications in the patients with
      progressive CRF through various treatments including oral administration or
      coloclysis of Chinese herbal medicine, oral administration combined with
      coloclysis of Chinese herbal medicine, and colonic dialysis combined with
      coloclysis of Chinese herbal medicine. Finally,it has been reviewed the
      beneficial influences of Chinese herbal medicine on metabolic dysequilibrium of
      calcium and phosphonium, microinflammatory state, and uremic toxins in patients
      with uremia.

PMID- 21842634
TI  - [Surveys on resources and varieties on Chinese markets of crude drug mahuang].
AB  - Many species of the genus Ephedra plants are used as Chinese traditional
      medicines, in Chinese which are known as "Mahuang" (Ephedrae Herba). In order to
      get a clear picture of resources distribution and varieties on Chinese markets of
      the crude drug Mahuang and provide scientific basis for their resource
      conservation and sustainable use, during recent years we conducted field
      investigations and market researches many times. The results showed that the most
      common species on the Chinese markets was E. sinica (33/38 commercial samples),
      followed by E. intermedia (5/38 commercial samples), which was also used in local
      clinics in Qing-hai, Gansu and Xinjiang province, no E. equisetina was found in
      the market. We noticed that the resources of both official and non-official
      plants of Mahuang, especially Zhong-Mahuang and Muzei-Mahuang, were seriously
      damaged in the past decade because of the ecological environment damage and over
      digging. Zhong-Mahuang was distinguished in Ningxia and north Gansu, which was
      once one of the most distribution areas and contains more than 10,000 t Zhong
      Mahuang. Muzei-Mahuang was distinguished in most places and distributed sparsely
      around Altay Mountains in northeast in Xinjiang. Thus, Cultivation of Mahuang,
      especially Zhong-Mahuang and Muzei-Mahuang should be greatly developed. At the
      same time, wild resources of Mahuang must be preserved strictly, i.e., proper
      method of cutting Ephedra plant could prevent the damage of the resource.

PMID- 21842635
TI  - [Responses of physiological ecology and quality evaluation of Rehmannia gltinosa
      in continuous cropping].
AB  - OBJECTIVE: To study responses of physiological ecology and quality evaluation of
      Rehmannia glutinosa in continuous cropping. METHOD: The potted plant R. glutinosa
      which consists of first cropping, 1 year continuous cropping and 2 year
      continuous cropping were used as experimental materials. The photosynthetic
      activity, descending axis vitality, the protective enzymes system and MDA content
      were measured, the quality was evaluated by FTIR and HPLC. RESULT: Continuous
      cropping reduced the content of chlorophyll in the non-first cropping R.
      glutinos, the photosynthetic activity and descending axis vitality were weakened.
      Because of the increase of the free radical in the R. glutinos due to the
      continuous cropping, the activity of protective enzymes including POD, SOD and
      CAT were enhanced and MDA content were increased, more importantly the medical
      potency declined . And along with the increasing years of the continuous
      cropping, this effect becomes even stronger. CONCLUSION: Continuous cropping
      affects the descending axis ability of absorbing water and nutrition and
      photosynthesis are inhibited R. glutinosa, at the same time, it also causes the
      disorders of antioxidation systems in R. glutinos, resulting in continuous
      cropping obstacle and decline of the medicinal materials quality.

PMID- 21842636
TI  - [Preliminary study on promoting effects of endophytic fungi to growth of
      Rehmannia glutinosa].
AB  - In previous studies, four endophytic fungi were isolated from different swollen
      roots of Rehmannia glutinosa. It's thought that Ceratobasidium sp. , one of the
      discovered endophytic fingi, was a major promoter for the growth of the roots. In
      this study, symbiotic experiments were performed to measure the effects of
      different endophytic fingi cultivated with R. glutinosa. The results showed that
      the R. glutinosa had significant increases in the size of roots and amount of
      chlorophyll cultivated with Ceratobasidium sp. And it was tested that
      indoleacetic acid secreted by Ceratobasidium sp. maybe the effective factor for
      the promotion of the growth.

PMID- 21842637
TI  - [Studies on macroscopic and microscopic identification of Cordyceps sinensis and
      its counterfeits].
AB  - OBJECTIVE: To provide a rapid, simple, accurate and reproducible identification
      method from which Cordyceps sinensis can be distinguished from other species.
      METHOD: To observe the larva and stroma of Cordyceps family with macroscopic
      identification method, and with powder microscopic identification method. RESULT
      AND CONCLUSION: For macroscopic, only stroma of C. sinensis is mostly non
      inflated, and un-obtuse at the tip, the caterpillar annulations of C. sinensis
      and the C. gracilis is distinct, about 20-30, and feet of above two are 8 pairs,
      4 of 8 pairs are relatively distinct. The above appearance shows its unique
      characteristic. For microscopic identification, only C. sinensis exists
      microtrichia, the tip is pointed. The arranging order of stubby setae is
      irregular, the tip is blunt while the basal is gradually broader; the top of some
      setae bends slightly like a hook.

PMID- 21842638
TI  - [Study on sequence characterized amplified region (SCAR) markers of Cornus
      officinalis].
AB  - OBJECTIVE: To establish sequence characterized amplified region markers of Cornus
      officinalis and provide a scientific basis for molecular identification of C.
      officinalis. METHOD: The random primer was screened through RAPD to obtain
      specific RAPD marker bands. The RAPD marker bands were separated, extracted,
      cloned and sequenced. Both ends of the sequence of RAPD marker bands were
      determined. A pair of specific primers was designed for conventional PCR
      reaction, and SCAR marker was acquired. RESULT: Four pairs of primers were
      designed based on the sequence of RAPD marker bands. The DNA of the seven
      varieties of C. officinalis was amplified by using YST38 and YST43 primer. The
      results showed that seven varieties of C. officinalis were able to produce a
      single PCR product. It was an effective way to identify C. officinalis. The
      varieties with cylindrical and long-pear shape fruits amplified by YST38 showed a
      specific band, which could be used as the evidence of variety identification.
      Seven varieties of C. oficinalis were amplified by using primer YST39. But the
      size of band of the variety with spindly shape fruit (35,0400 bp) was about 300
      bp, which was shorter than those of the variety with the other shape fruits of C.
      officinalis (650-700 bp). The variety with the spindly shape fruit could be
      identified through this difference. The primer YST92 could produce a fragment
      from 600-700 bp in the varieties with cylindrical and long-pear shape fruits, a
      fragment from 200-300 bp in the varieties with oval and short-cylindrical shape
      fruits and had no fragment in the varieties with long cylindrical, elliptic and
      short-pear shape fruits, which could be used to select the different shapes of C.
      officinalis. CONCLUSION: SCAR mark is established and can be used as the basis
      for breeding and distinguishing the verieties of C. officinalis.

PMID- 21842639
TI  - [Comparasion of polysaccharides in parent root, daughter root and rootlet of
      Aconitum carmichaeli].
AB  - OBJECTIVE: To study the polysaccharides contents and monosaccharide compositions
      in parent root, daughter root and rootlet of Aconitum carmichaeli. METHOD: The
      conversion coefficient of A. carmichaeli polysaccharide to glucose was obtained
      by refined polysaccharides, and then the contents of crude polysaccharides in
      parent root, daughter root and rootlet were determined by sulfuric-phenol
      spectrometry method; analysis of monosaccharide compositions in polysaccharides
      from A. carmichaeli was carried out by pre-column derivatization high performance
      liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone (PMP). RESULT: The
      contents of polysaccharides in parent root, daughter root and rootlet were
      22.02%, 33.53% and 6.10%, respectively. Parent root, daughter root and rootlet
      mainly contained glucose, and in addition they contained a small amount of
      galacturonic acid, galactose and arabinose. Daughter root contained mannose yet,
      and rootlet still contained mannose, rhamnose and xylose. CONCLUSION: The method
      is simple, rapid, and accurate. The content of polysaccharide in rootlet is
      lowest, and monosaccharide compositions in rootlet are significantly different
      from parent root and daughter root.

PMID- 21842640
TI  - [Rapid analysis of psoralen and isopsoralen in Psoralea corylifolia by microwave
      assisted extraction].
AB  - OBJECTIVE: To establish a convenient and rapid method of microwave-assisted
      extraction (MAE) for the extraction of psoralen and isopsoralen in Psoralea
      corylifolia. METHOD: The effects of various parameters on the MAE were
      investigated with several single-factor tests, and compared with the traditional
      extraction. RESULT: The optimal conditions of MAE were as follows: the extractine
      time was 3 min, and the ratio of solvent to material was 400 mL x g(-1) by using
      methanol as the solvent. Compared with soxhlet extraction, heat reflux
      extraction, and ultrasound-assisted extraction, MAE needed only 3 min to give the
      highest yield of psoralen and isopsoralen, while the other extraction methods
      needed several hours and gave lower yield. CONCLUSION: The proposed method has
      greatly shortened extraction time and improved extraction yield, so it provides a
      neotype, simple and rapid measure for the separation of psoralen and isopsoralen
      from P. corylifolia.

PMID- 21842641
TI  - [Study on quality control of herbal material of paeony formula granule by near
      infrared diffuse reflection spectroscopy].
AB  - OBJECTIVE: To develop a novel method to determine fastly and nondestructively the
      content of paeoniflorin, albiflorin and moisture in Radix Paeoniae Alba with near
      infrared diffuse reflection spectroscopy. METHOD: Multivariate calibration models
      based on PLS algorithm were developed to correlate the spectra and the
      corresponding values determined by the reference method. RESULT: The corelation
      coefficients (R2) of the calibration models were 0.938, 0.943 and 0.976, and the
      prediction average relative deviation for paeoniflorin, albiflorin and moisture
      content were 6.5%, 0.23% and 3.8%, respectively. CONCLUSION: The NIRS
      determination method is rapid, accurate, nondestructive and non-pollution. It can
      dispose the samples without complicated pretreatment. It is qualified to analyze
      rapidly traditional Chinese medicine whose components are complex. NIRS can be
      used to control the quality of herbal material of paeony formula granule.

PMID- 21842642
TI  - [Preparation and anti-oxidant activity of cinnamic acid derivatives-g-CTS].
AB  - OBJECTIVE: To prepare cinnamic acid derivatives-g-CTS and to study its
      antioxidation activity. METHOD: The ability of catching oxygen of the products
      and raw material were determined through two methods, Marklund method and trace
      pyrogallic acid method, with autoxidation reaction of pyrogallol as the oxygen
      anion source. RESULT: The antioxidation activities of all products were better
      than the raw material. CONCLUSION: Cinnamic acid derivatives-g-CTS is suitable as
      the O2-* -capture agent.

PMID- 21842643
TI  - [Comparison of acute toxicity of extract of unprocessed indian atringbush root
      and its two different processed products].
AB  - OBJECTIVE: To compare the acute toxicity and content of daphnoretin among
      extracts of unprocessed indian string-bush root and its two different processed
      products, and to provide a basis for discussion of the mechanism of two processed
      methods. METHOD: Extracts of unprocessed indian stringbush root and processed
      indian stringbush root with "sweat" and "artificial sweat" were prepared. The
      mice were intragastrically administrated once with these three extracts, the
      mortalities of mice were observed, and the median lethal dose (LD50) of different
      extracts were calculated with Bliss method. The determination of daphnoretin in
      these three samples was performed by high performance liquid chromatography.
      RESULT: The LD50 of indian stringbush root extracts, indian stringbush root
      processed with "sweat" and with "artificial sweat" were 46.678, 72.190, 67.953 g
      x kg(-1), respectively. The contents of daphnoretin in unprocessed indian
      stringbush root, indian stringbush root processed with "sweat" and with
      "artificial sweat" were 0.189%, 0.407% and 0.345%, respectively. CONCLUSION: The
      toxicity of indian stringbush root processed with both "sweat" and "artificial
      sweat" is lower than that of the original rude drug. But the decreasion of
      toxicity of processed products is not by the reduced daphoretin content.

PMID- 21842644
TI  - [In vivo transmigration of active ingredients from Gastrodia elata in
      dachuanxiong fang].
AB  - OBJECTIVE: To investigate the substance basis of Gastrodia elata in Dachuanxiong
      Fang (DF) by serum pharmacochemistry, so that the quality of DF as well as its
      preparations can be effectively and systemically controlled. METHOD: The
      chromatographic peaks of blank plasma, blank cerebrospinal fluid, drug-contained
      plasma and cerebrospinal fluid were compared by HPLC fingerprints. The absorbed
      ingredients of the active parts extracted from G. elata were structurally
      identified by HPLC-DAD-MS". RESULT: Two components, which were definitely
      detectable in rat plasma following the oral administration of the active parts
      from G. elata, were identified as gastrodin and parishin. In rat cerebrospinal
      fluid, there are, however, no obvious peaks that belong to the ingredients from
      G. elata. CONCLUSION: Research on in vivo transmigration of ingredients from G.
      elata is favorable to the clarification of its active substance basis.

PMID- 21842645
TI  - [Removal of plumbum ion from the extract of Lonicera japonica by gamma
      mercaptopropyl-modified silica gel].
AB  - OBJECTIVE: To remove plumbum ion from the extract of Lonicera japonica by gamma
      mercaptopropyl-modified silica gel (MPS). METHOD: The reference plumbum ion
      solution was added into the extract of L. japonica as the tested samples. The
      static and dynamic adsorptions were investigated to evaluate the influent factors
      on the removal of plumbum ion in the extract. The solid content and HPLC profiles
      of the extract were determined to evaluate the process changes. RESULT: MPS
      showed excellent adsorption charateristics to remove plumbum ion from the extract
      of L. japonica, with fast adsorption rate and more than 80% removal efficiency.
      The optimum parameters were as follows: 6 times sample volume, 10 times of height
      to diameter, and 6 BV x h(-1) of flow velocity, at the temperature of 25 degrees
      C. During the removal process, obvious changes of solid content and HPLC profiles
      were not observed. CONCLUSION: MPS could be used to remove plumbum ion from
      extract of L. japonica.

PMID- 21842646
TI  - [Liposoluble constituents from Iodes cirrhosa and their neuroprotective and
      potassium channel-blocking activity].
AB  - OBJECTIVE: To study the chemical constituents of Iodes cirrhosa and evaluate
      their bioactivity. METHOD: The compounds were isolated and purified by various
      kinds of column chromatography methods and their structures were determined by
      spectroscopic data analysis. Neuroprotective assay against serum deprivation
      induced SH-SYSY-JNK3 cell apoptosis was evaluated by MTr method while potassium
      channel-blocking activity was assayed in both non-specific and specific K+
      channel-regulator screening models. RESULT: Twenty-one compounds were obtained
      from an EtOAc portion of an ethanolic extract of the root of I. cirrhosa. Their
      structures were elucidated as 1beta, 3beta-dihydroxyurs-9(11),12-diene(1),
      bauerenyl acetate(2),3beta-hydroxy-11-oxo-olean-12-enyl palmitate(3), 3beta
      acetoxy-urs-12-ene-11-one(4), betulinic acid(5), stigmasta-5, 22-diene-3beta
      ol(6), 7beta-hydroxystigmasterol(7), stigmasta-5, 22diene-3beta-ol3-O-beta-D
      glucopyranoside(8),scopoletin(9),scopolin(10),clovamide(11),methyl 3,5-di-O
      caffeoylquinate(12),3,5-dicaffeoylquinic acid(13),2,6-dimethoxy-1,4
      benzoquinone(14), protocatechualdehyde(15), vanillin(16), protocatechuic
      acid(17), vanillic acid(18),caffeic acid(19),azelaic acid(20),and succinic
      acid(21). Compound 3,4,6,9,10,14,15,18 and 20 showed neuroprotective activities
      against serum deprivation induced SH-SYSY-JNK3 cell apoptosis at a concentration
      of 1.0 x 10(6) mol x L(1) with relative protection rates of 177%, 144%, 137%,
      137%, 143%, 145%, 137%, 189%, 130%, respectivley. Compound 16 could increase
      DiBAC4(3) fluorescence response in both non-specific and specific K+ channel
      regulator screening models at the concentration of 1.0 x 10(-5) mol x L(-1).
      CONCLUSION: Compound 1 was a new compound and all compounds were isolated from
      this genus for the first time. Compounds 3,4,6,9,10,14,15,18 and 20 showed
      neuroprotective activities while 16 exhibited K+ channel-blocking activity.

PMID- 21842647
TI  - [Alkaloids and anthraquinones from branches and leaves of uvaria kurzii].
AB  - OBJECTIVE: To investigate the chemical constituents of the branches and leaves of
      Uvaria kurzii. METHOD: The compounds were isolated and purified by silica gel and
      Sephadex LH-20 column chromatographic methods. Their chemical structures were
      elucidated on the basis of physicochemical properties and spectral data. RESULT:
      Nine compounds were isolated and identified as: bidebiline A(1), annobraine (2),
      oxoputerine (3), atherospermidine (4), liriodenine (5), physcion (6), questin
      (7), rubiadin 3-methyl ether (8), emodin (9). CONCLUSION: Compound 1-4, 6-9 were
      isolated from the genus Uvaria for the first time. Compound 3-5 showed
      inhabitation activities against tumor cell lines A549, Bel7402, BGC823, HCT-8,
      A2780, respectively.

PMID- 21842648
TI  - [Studies on chemical constituents in roots of Helicteres angustifolia].
AB  - OBJECTIVE: To study the chemical constituents of the roots of Helicteres
      angustifolia. METHOD: The compounds were isolated and purified by column
      chromatographic methods on silica gel, Sephadex LH-20, ODS and preparative HPLC.
      Their structures were elucidated on the basis of physicochemical properties and
      spectral data. RESULTS: Fourteen compounds were isolated from this plant. Their
      structures were identified as methyl helicterate(1),3-acetoxybetulin(2),3beta
      acetoxy-27-(p-hydroxyl)benzoyloxylup-20(29)-en-28-oic acid methyl ester(3),3beta
      acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid(4),3beta-acetoxybetulinic
      acid(5),pyracrenic acid(6),cucurbitacin D(7),cucurbitacin B(8),isocucurbitacin
      D(9),3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl ester
      (10),beta-sitosterol(11),2alpha,7beta,20alpha-trihydroxy-3beta,21-dimethoxy-5
      pregnene(12), hexadecanoic acid(13), and daucosterol(14), respectively.
      CONCLUSION: Compounds 5,8,9,13, 14 were isolated from this plant for the first
      time.

PMID- 21842649
TI  - [Chemical constituents from Exochorda racemosa].
AB  - OBJECTIVE: To study the chemical constituents of Exochorda racemosa. METHOD:
      Compounds were isolated and purified by silica gel, Sephadex LH-20, MCI gel and
      RP-18 column chromatography, and their structures were determined by
      spectroscopic analysis. RESULT: Twenty compounds were isolated and identified as
      N-p-coumaroyl-N'-caffeoylputrescine (1), sutherlandin trans-p-coumarate (2),
      apigenin 7-O-methylglucuronide (3), astragalin (4), nicotiflorin (5), kaempferol
      3-neohesperidoside (6), rutin (7), apigenin (8), luteolin (9), linalool-1-oic
      acid (10), betulalbuside A (11), ursolic acid (12) , corosolic acid (13),
      gynuramide II (14), beta-sitosterol (15), daucosterol (16), uridine (17),
      adenosine (18), syringin (19), and trans4-hydroxycinnamic acid (20),
      respectively. CONCLUSION: All compounds were obtained from this plant for the
      first time, moreover, 1 was reported as a new natural product, and 2 is a
      naturally rare cyanogenic glycoside.

PMID- 21842650
TI  - [HPLC characteristic fingerprint of Moghania philippinensis root].
AB  - OBJECTIVE: To study HPLC characteristic fingerprint of Moghania philippinensis
      and provide a reliable method for scientific evaluation and quality control.
      METHOD: The chromatographic separation was performed on a Kromasil C15 column
      (4.6 mm x 250 mm, 5 microm). The mobile phase consisted of acetonitrile and water
      containing 0.3% acetic acid in gradient elution. The column temperature was set
      at 40 degrees C and the detection wavelength was at 254 nm. RESULT: The developed
      HPLC fingerprint method above was applied to analyze 23 batches of crude herbs of
      Moghania philippinensis. The total 22 peaks were selected as the characteristic
      peaks. And five of them were identified as genistein, genistin, 5,7,3',4'
      tetrahydroxy-6,8-diprenylisoflavone, 5,7,4'-trihydroxy-6,8-diprenylisoflavone and
      flemiphilippinin E by matching their retention time, UV spectra data with those
      of the authentic chemical reference substances. CONCLUSION: The method is simple,
      accurate and reproducible. It is suitable for the quality control of M.
      philippinensis.

PMID- 21842651
TI  - [Proteomic research on anti-atherosclerosis mechanism of curcumin in RAW264.7].
AB  - OBJECTIVE: Two-dimensional difference gel electrophoresis and mass spectrum were
      used to study the anti-atherosclerosis mechanism of curcumin. METHOD: The
      proteins from RAW264.7 cell and RAW264.7 cell treated with 25 micromol x L(-1)
      curcumin were labeled with Cy3 or Cy5 randomly. Each Cy3-labeled sample and Cy5
      labeled sample was mixed on the same 2-D gel along with a Cy2-labeled mixture of
      all samples as an internal standard and run on the same gel. The gels were
      scanned under different wave-length light after electrophoresis. All images were
      analyzed by DeCyder 6.5 software, and the different proteins were identified by
      mass spectrum. RESULT: The expression of ATP synthesis H+ transporting, MHC class
      II, non-muscle myosin alkali light chain and cytochrome b5 increased in the
      RAW264.7 cell treated with 25 micromol x L(-1) curcumin, while the expression of
      phosphodiesterase 4D, elF-3, Hnrpf protein, vimentin, nucleophosminl and Ranbp 1
      decreased. CONCLUSION: The anti-atherosclerosis mechanism of curcumin is the
      result of enhancement of the cell inflammation, antioxidant activity and
      inhibition of cholesterol transport, reduce of the accumulation of intracellular
      cholesterol and other factors. In addition, curcumin also had the effect of anti
      tumor through regulated tumor cell differentiation and apoptosis.

PMID- 21842652
TI  - [Researches on pyretic pulmonary syndrome model interfered by Scutellariae Radix
      based on variation of biomarker].
AB  - OBJECTIVE: Metabonomics researches of Scutellariae Radix interfering pyretic
      pulmonary syndrome had been done, to determine the specific biomarkers of pyretic
      pulmonary syndrome, and to approach the mechanism that Scutellariae Radix
      interfered the variation of these biomarkers. METHOD: Metabonomics technique,
      UPLC-Q-TOF/MS analytical means and PCA statistical methods were utilized to
      investigate the trajectory change and inter-relationship of urinary metabolome of
      rats treated differently. RESULT: Six specific biomarkers were determined which
      could represent Streptococcus pneumoniae-induced pyretic pulmonary syndrome in
      rats. Scutellariae Radix could significantly adjust the ascended biomarkers to
      the normal level. Meanwhile two of these biomarkers were identified as Delta-12
      prostaglandin J2 and indoxyl sulfate. CONCLUSION: There was a good therapeutic
      function of Scutellariae Radix on pyretic pulmonary syndrome, which was
      elucidated on the metabolic aspects. There was also a correlationship between the
      mechanism of Scutellariae Radix curing pyretic pulmonary syndrome and the six
      specific biomarkers.

PMID- 21842653
TI  - [Gambogenic acid inhibits proliferation of A549 cells through apoptosis
      inducing].
AB  - To explore gambogenic acid (GNA)-induced apoptosis and underlying mechanism in
      vivo. A549 nude mice xenografts were used as in vivo model to study anticancer
      effect of GNA by observing tumor growth curve and weight of the tumor.
      Ultrastructure of A549 cells treated by GNA was observed by TE. Expression of COX
      2 and VEGF were detected by immunohistochemistry. TUNEL assay was applied in
      examining apoptosis index of tumor cells. The tumor isolated from mice treated by
      GNA (8, 16 mg kg(-1)) took on a slow growth condition compared with control
      group. The results suggested that weight and volume of the tumor from
      experimental groups were remarkably decreased compared with control group (P <
      0.05). Ultrastructure change of the tumor, such as vacuolization, abnormal
      distribution of the heterochromosome, volume of the tumor cells, even apoptotic
      bodies, were observed in GNA-treated group. While no apparent morphological
      change was observed in the normal group. Typical apoptotic characteristics could
      be distinctly observed in the mouse treated by GNA for 20 days and apoptosis
      index in GNA-treated group was significantly higher than model group. Expression
      of COX-2 and VEGF were significantly down-regulated in GNA-treated groups in
      comparison with control group (P < 0.01). These results indicate that GNA could
      affect the development and progression of A549 cells through inducing apoptosis,
      mediating the expression of VEGF in vascular cells and COX-2 in tumor cells.

PMID- 21842654
TI  - [Protective effects of puerarin against 1-methyl-4-phenylpyridinium-induced
      mitochondrial apoptotic death in differentiated SH-SY5Y cells].
AB  - It is well known that puerarin possesses protective activity on neurodegenerative
      diseases. However, the exact path way involved in the protective effect of
      puerarin on MPP+ -induced cell death is unclear. In this study, we focused on
      mitochondria im pairment in the apoptotic process of MPP+ -elicited SH-SY5Y cells
      and detected the protection of puerarin. As evidenced by Trypan blue assay, the
      cell viability was significantly decreased by 1 mmol x L(-1) MPP+, but reversed
      by different concentrations puerarin pre treatment. Flow cytometer analysis
      revealed that MPP+ -induced SH-SY5Y cells apoptosis and arrested the cells in
      G2/M phase, where as puerarin pretreatment concentration dependently reversed the
      apoptosis ratio. In addition to the apoptosis ratio, 50.0 micromol x L(-1)
      puerarin pretreatment even altered the MPP+ -induced G2/M phase arrest. JC-1
      assay suggested that MPP+ significantly opened MMP of the SH-SYSY cells;
      pretreatment with puerarin attenuated the deterioration of the MMP. Both ELISA
      and Western blotting showed that puerarin prevented the release of cytochrome c
      from the mitochondrial interior to the cystol elicited by MPP+. DNA ladder showed
      that typical DNA ladder was present in the MPP+ -induced SH-SY5Y cells.
      Additionally, MPP+ enhanced caspase-9 and caspase-3 ac tivity, respectively,
      while not caspase-8. However,the enhancement was concentration dependently
      blocked by puerarin pretreatment. Taken together, puerarin can modulate
      mitochondrial membrane potential and inhibit the cytochrome c releasing-caspase
      cascade to pre vent MPP+ -induced cell injury.

PMID- 21842655
TI  - [Influences of Oxytropis falcata on proliferation of SMMC-7721 hepatocarcinoma
      cells and expression of MMP-2].
AB  - OBJECTIVE: To investigate the influences of extracts of Oxytropis falcata on
      proliferation of SMMC-7721 cells and expression of MMP-2 (matrix
      metalloproteinase-2). METHOD: SMMC-7721 cells were treated for 24 h with five
      fractions obtained from 0. falcata in different concentrations. Inhibition on
      proliferation of the SMMC-7721 cells was assessed by MT method. Secretion of MMP
      2 was measured by ELISA in the supernatant of SMMC-7721 cells treated with
      fractions of essential oil and total flavonoids for 24 h. Transcription of mRNA
      of MMP-2 was detected by Real-time PCR. RESULT: In MT assay, essential oil and
      total flavonoids showed potential antiproliferative activity on SMMC-7721 in a
      concentration dependent manner. Data of ELISA showed that fraction of essential
      oil suppressed secretion of MMP-2 significantly. Results of Real-time PCR
      indicated that both essential oil and total flavonoids restrained expression of
      mRNA of MMP-2. CONCLUSION: It suggested that essential oil and total flavonoids
      of O. falcata inhibit proliferation of SMMC-7721 cells through down-regulating
      secretion and expression of MMP-2 in cells. However, further experiments are
      necessary to carry out to investigate the potential mechanism.

PMID- 21842656
TI  - [Glossy ganoderma spore oil promotes apoptosis of human lung adenocarcinoma SPC
      A1 through downregulation of miR-21].
AB  - OBJECTIVE: To investigate the effects of glossy ganoderma spore oil on the
      proliferation, apoptosis, expression of miR-21 and its target genes of human lung
      adenocarcinoma SPC-A1 cell line, and to explore its possible mechanism. METHOD:
      The SPC-A1 cells were treated with glossy ganoderma spore oil for 24 and 48
      hours. The inhibition growth efficacy was determined using cell count kit (CCK
      8). Cell morphological changes were observed by light microscopy. Cell apoptosis
      was analyzed by flow cytometry. The expression of miR-21, PTEN and PDCD4 were
      determined by Real-time PCR. RESULT: Glossy ganoderma spore oil concentration
      dependently inhibited the SPC-A1 cell's proliferation. When the concentration of
      glossy ganoderma spore oil attained to 0.2%, the cells' morphology changed
      obviously. Glossy ganoderma spore oil could induce the apoptosis of SPC-A1 cells
      at low concentration. Glossy ganoderma spore oil down-regulated the expression of
      miR-21 and up-regulated the expression of PTEN and PDCD4 significantly.
      CONCLUSION: glossy ganoderma spore oil could inhibit the proliferation obviously
      and cause the changes of cell morphology. Furthermore, glossy ganoderma spore oil
      induced apoptosis of SPC-A1 cell through down-regulating the expression of miR-21
      and up-regulating tumor suppressors.

PMID- 21842657
TI  - [Influence of iridoid from Valeriana jatamansi on 5-HT and 5-HIAA in rats with
      irritable bowel syndrome].
AB  - OBJECTIVE: To investigate the mechanism of iridoid from Valeriana jatamansi
      treating irritable bowel syndrome. METHOD: Sixty male SD rats were equally
      divided into 6 groups (2 controls, 1 model and 3 treatment doses) with 10 rats
      per group. The test groups were administered with iridoid (24.92, 12.46, 6. 23 mg
      x kg(-1)) while the control groups were administered with fluoxetine (2.5 mg x
      kg(-1), positive control) or distilled water (negative control). The model was
      established by chronic stress and independent feeding. The influence of iridoid
      from V. jatamansi on 5-HT and 5-HIAA in colon, serum and hypothalamic were
      observed in all groups. RESULT: In the model group, the content of 5-HT in colon
      and serum increased significantly, but the content of 5-HT in hypothalamic
      decreased significantly. The content of 5-HIAA and the value of 5-HT/5-HIAA had
      no significant change. In three iridoid-treated groups, the content of 5-HT in
      colon and serum decreased, but the content of 5-HT in hypothalamic increased. The
      content of 5-HIAA had no significant change. The value of 5-HT/5-HIAA in colon
      and serum reduced. CONCLUSION: The mechanism of iridoid from V. jatamansi
      treating irritable bowel syndrome may be related to the regulation effect to the
      levels of 5-HT from Gastrointestinal to central nervous system.

PMID- 21842658
TI  - [Therapeutic effects of saponins from Achyranthes bidentata in SHRsp].
AB  - OBJECTIVE: To study the therapeutic effects of saponins from Achyranthes
      bidentata (SAB) in stroke-prone sponyaneously hypertension rats (SHRsp). METHOD:
      Sixty SHRsp were randomly divided into five groups: SAB 0.10, 0.20, 0.40 g x kg(
      1), Huatuo Zaizao pill group (positive control group) 2.5 g x kg(-1) and
      pathologic group (n=10). SAB and Huatuo Zaizao pill were used through filing
      stomach everyday for 20 days, pathologic group was given distilled water. The
      effects of SAB on blood pressure, changes of nerve state, death rate, brain index
      and the pathologic changes of hippocampal neuron of SHRsp were observed. RESULT:
      SAB could markedly decrease brain index, death rate of SHRsp after stroke. SAB
      could improve nerve state of SHRsp after stroke. Also SAB could prolong survival
      time and prevent pathologic change of hippocampal neuron of SHRsp after stroke.
      CONCLUSION: SAB is advantageous of therapying the stroke in SHRsp.

PMID- 21842659
TI  - [UPLC-MS analysis of constituents of dachuanxiong fang active parts absorbed into
      blood].
AB  - OBJECTIVE: To study the constituents absorbed into blood following the
      intragstric administration of Dachuanxiong Fang active parts(DCXF) to the
      experimental migrainous model rats induced by nitroglycerin. METHOD: The UPLC-MS
      was used as the analytic method. The DCXF, Chuanxiong active parts, Tianma active
      parts, gastrodin, ferulic acid and senkyunolide I were used as the control
      samples. The information on the total ion chromatogram, mass chromatogram and the
      mass spectrogram were synthetically analyzed to confirm the constituents absorbed
      into blood. RESULT: Ten of the DCXF constituents were detected in the rats plasma
      post the intragastric administration of DCXF, in whitch four including gastrodin
      came from Tianma active parts and six including ferulic acid and senkyunolide I
      from Chuanxiong active parts. CONCLUSION: The findings abtained from the study
      can provide the useful information for the determination of bioactive substances
      of the DCXF.

PMID- 21842660
TI  - [Investigation on pattern of quality control for Chinese materia medica based on
      famous-region drug and bioassay--the work reference].
AB  - Selection and standardization of the work reference are the technical issues to
      be faced with in the bioassay of Chinese materia medica. Taking the bioassay of
      Coptis chinensis. as an example, the manufacture process of the famous-region
      drugs extraction was explained from the aspects of original identification,
      routine examination, component analysis and bioassay. The common technologies
      were extracted, and the selection and standardization procedures of the work
      reference for the bioassay of Chinese materia medica were drawn up, so as to
      provide technical support for constructing a new mode and method of the quality
      control of Chinese materia medica based on the famous-region drugs and bioassay.

PMID- 21842661
TI  - The organization of thanatology.
AB  - This article explores, using Wilensky's Model of Professionalization, the
      emergence of professional organizations within the thanatology. The authors
      review the history of four organizations--The Foundation of Thanatology, Ars
      Moriendi, The Forum for Death Education and Counseling (now the Association for
      Death Education and Counseling: A Thanatology Organization [ADEC]), and The
      International Work Group on Death, Dying, and Bereavement (IWG). The authors
      speculate on some of the reasons that the first two failed while IWG and ADEC
      remain viable-while noting challenges that these remaining thanatological
      organizations will experience as they seek to continue to stay relevant.

PMID- 21842662
TI  - Relationship to the bereaved and perceptions of severity of trauma differentiate
      elements of posttraumatic growth.
AB  - The field of bereavement and grief has been expanding to recognise the potential
      for growth following the loss of a loved one. This study sought to examine the
      effect of the relationship to the deceased and perceptions of the severity of the
      trauma on dimensions of posttraumatic growth. Participants were 146 people who
      had lost either: a) a first degree relative, b) a second degree relative, or c) a
      non-related friend. Results demonstrated that both severity and the relationship
      to the bereaved differentiate posttraumatic growth outcomes. For example,
      participants who had lost a first degree relative reported higher levels of
      growth than those who had lost a second degree relative. Consistent with previous
      research in general trauma populations, the more severe the loss was rated, the
      higher the levels of growth. Implications for practice are discussed.

PMID- 21842663
TI  - Coping with the ultimate deprivation: narrative themes in a parental bereavement
      support group.
AB  - Support groups are often used to help individuals cope with challenging and
      unusual life circumstances through narration. Yet, little is known about specific
      meta-communication within a support group setting and in what ways these
      interactions may benefit participants. This study uncovers narrative themes that
      were expressed during a series of support group meetings specific to bereaved
      parents. Three central narratives were revealed in the analysis including the
      death story narrative, coping/negotiating narrative, and connecting through
      communication with others narrative. This research underscores the vital outlet
      that the support group serves for participants and the communicative means by
      which subjective healing can occur.

PMID- 21842664
TI  - Surviving grief: An analysis of the exchange of hope in online grief communities.
AB  - Online grief communities represent relatively new forms of peer support. However,
      the degree to which they are helpful for individual grieving processes is
      unknown. To date, no research has evaluated the type or quality of support
      exchanged in online grief communities. To begin to address these questions, this
      study analyzed 564 messages from internet grief websites to: (1) classify the
      type of helping skills used, and (2) extract themes contained in the content of
      the messages. Messages selected for analysis were the first response to an
      original post, assuming they would be the first effort to provide support to a
      grieving individual. Results revealed a majority of responses contained self
      disclosure. Themes in the messages suggested provision of more than "one-way"
      support; messages themes also included exchanging hope for the future by sharing
      one's own story, validating the grief experience, providing resources, and
      exchanging psychosocial support. Clinical implications and research
      recommendations are discussed.

PMID- 21842665
TI  - Perinatal loss and parental grief: the challenge of ambiguity and disenfranchised
      grief.
AB  - Following perinatal loss, a type of ambiguous loss, bereaved couples struggle
      with and experience distress due to various forms of ambiguity. Moreover, the
      juxtaposition of their grief with society's minimization often disenfranchises
      them from traditional grieving processes. The purpose of this study was to
      explore sources of ambiguity and disenfranchised grief related to perinatal loss.
      Audio-taped interviews with 13 bereaved couples at 2, 6, and 13 months following
      the death of their fetus or infant were analyzed. Several categories of ambiguity
      and disenfranchised grief emerged, pertaining to: (a) the viability of the
      pregnancy; (b) the physical process of pregnancy loss; (c) making arrangements
      for the remains; and (d) sharing the news. This study uncovers the many sources
      of ambiguity and disenfranchised grief that bereaved couples face in interactions
      with family, friends, society, and healthcare professionals. These insights may
      inform healthcare professionals in their attempts to ease distress related to
      perinatal loss.

PMID- 21842666
TI  - [Results of Norwood type operation for interrupted aortic arch complex; surgical
      decision making].
AB  - BACKGROUND: Interrupted aortic arch (IAA) is associated with a multitude of
      lesions ranging from isolated ventricular septal defect to hypoplastic left
      ventricle or severe subaortic stenosis (SAS). Left ventricular outflow
      obstruction such as SAS continues to be an important factor for deciding the
      surgical procedure between univentricular and biventricular repairs. METHODS: A
      retrospective study was conducted in 8 consecutive infants aged 14 to 117 days
      and operated on between 2004 and 2009. Seven patients had undergone bilateral
      pulmonary artery banding for pulmonary high flow regulation. All patients
      underwent Norwood-type operation (4 with systemic to pulmonary artery shunt, 3
      with right ventricle to pulmonary artery shunt, and 1 with bidirectional Glenn
      shunt). RESULTS: One patient died 2 months after surgery due to respiratory
      failure. The others were discharged in a good condition. One patient underwent
      Rastelli-type operation and biventricular circulation was achieved. The other 6
      patients were all Fontan candidates. CONCLUSION: Satisfactory initial palliation
      can be achieved by Norwood-type operation for IAA with severe SAS or hypoplastic
      left ventricular-aortic complex.

PMID- 21842667
TI  - [Stump consolidation after video-assisted thoracoscopic segmentectomy].
AB  - Pulmonary segmentectomy by video-assisted thoracic surgery (VATS) is used for
      minimally invasive surgery for removal of small lung neoplasms, and stump
      consolidation is one of the potential postoperative complications. The objective
      of the present study is to clarify the incidence of stump consolidation and its
      predictive factors by assessing patients who underwent VATS segmentectomy in our
      department. Stump consolidation was defined as atelectatic lesions along the
      surgical stump with >10 mm thickness in horizontal sectional view by computed
      tomography, at least 3 months after surgery. Between February 2007 and September
      2010, 70 patients (38 men and 32 women) with primary lung cancer (43 patients)
      and metastatic pulmonary tumor (27 patients) underwent VATS segmentectomy. Stump
      consolidations were seen in 7 patients. Univariate analysis showed the
      significant difference for the period of performed operation. Left-sided
      operation, especially segmentectomy of left S(1+2), was another predictive
      factor, though not significant. Stump consolidation after VATS segmentectomy can
      be deueloped by conbined workspace for stapling and misidentification of
      intersegmental plane. When division of the intersegmental plane is difficult,
      open thoracotomy should be undertaken to prevent such compliance.

PMID- 21842668
TI  - [New technique of bilateral pulmonary artery banding using half-closed surgical
      clips; an experimental study].
AB  - Bilateral pulmonary artery banding (PAB) using constrictive tapes encircled
      around both pulmonary arteries entails frequent post-debanding residual pulmonary
      artery stenosis. We devised a new technique of bilateral PAB using half-closed
      surgical clips. Surgical clips, applied half-closed around both pulmonary
      arteries, transform the cross sections of the pulmonary arteries into diamond
      shapes, and reduce their cross sectional areas without significantly reducing
      their circumferences. Animal experiment using beagles indicated that bilateral
      PAB using half-closed surgical clips is technically feasible and reproducible,
      causes less pulmonary arterial intimal proliferation and entails lower risk of
      residual pulmonary artery stenosis than bilateral PAB using constrictive tapes.

PMID- 21842669
TI  - [Three-dimensional display simulation of lung surgery using "active shutter
      glasses"].
AB  - We have reported preoperative 3-dimensional (3D) simulation of thoracoscopic lung
      surgery using self-made software and internet shareware of 3D-modeler. Using
      "active shutter glasses", we have tried the "3D display simulation" of lung
      surgery. 3D display was more effective to grasp clear 3D interrelation between
      the bronchii and pulmonary vascular system than those in images of currently in
      use with the same information volume.

PMID- 21842670
TI  - [Acute massive pulmonary thromboembolism with cardiac arrest].
AB  - Acute massive pulmonary thromboembolism (APE) is still associated with a high
      mortality rate. Furthermore, significantly higher mortality rates are observed in
      patients who underwent cardiopulmonary resuscitation (CPR) because of severe
      brain damage or multiple organ failure. We present successfully treated 4
      patients who were transferred from outside hospitals under continuous CPR. Three
      of 4 patients required percutaneous cardiopulmonary support (PCPS).
      Preoperatively, all 4 patients had no brain damage despite of CPR for a maximum
      of 40 minutes. Open pulmonary thrombectomy was successfully performed under on
      pump beating cardiopulmonary support. All patients dramatically improved and were
      discharged without any complication. When hemodynamic instability or cardiac
      arrest occurs in patients with APE, rapid CPR, rapid diagnosis with
      echocardiography, and quick PCPS establishment are keys in our management
      strategy.

PMID- 21842671
TI  - [Successful preoperative respiratory rehabilitation in patients with aortic valve
      stenosis associated with severe respiratory dysfunction].
AB  - We describe 2 cases of aortic valve stenosis with severe pulmonary dysfunction.
      Preoperative respiratory rehabilitation programmed by the rehabilitation doctors
      was cautiously undertaken to improve their exercise tolerance and respiratory
      reserve. These 2 patients underwent aortic valve replacement eventually.
      Postoperative course in each patient was uneventful without respiratory
      complication. Preoperative respiratory rehabilitation can be performed in the
      high risk patient with severe pulmonary dysfunction as long as careful risk
      management is guaranteed.

PMID- 21842672
TI  - [Total arch replacement using a long elephant trunk for chronic dissecting
      aneurysm of a distal aortic arch].
AB  - A 74-year-old man was diagnosed with Stanford type B early thrombosed aortic
      dissection. Computed tomography (CT) 2 years later revealed that an aneurysm of
      the distal arch had enlarged from a maximal diameter of 47 mm to 62 mm and
      involved the descending aorta. Total arch replacement using a quadrifurcated arch
      graft proceeded through a median sternotomy under deep hypothermic
      cardiopulmonary bypass (20 degrees C) and selective brain perfusion. The long
      elephant trunk of another prosthesis was inserted into the descending aorta and a
      distal anastomosis was constructed immediately after the left common carotid
      artery. The post-operative course was uneventful and CT at that time revealed
      complete thrombo-exclusion of the aneurysm surrounding the long elephant trunk.
      This method was very useful for reducing the duration of circulatory arrest and
      bleeding, as well as the risk of postoperative complications.

PMID- 21842673
TI  - [Coronary artery stenting as a bridge to surgery in a patient with Stanford type
      A acute aortic dissection involving left main trunk of coronary artery].
AB  - An 80-year-old woman was transferred to our hospital with sudden onset of chest
      pain. Electorocardiogram (ECG) showed ST-segment elevation of VI-V3 and aV(L)
      leads suggestive of acute coronary syndrome. On emergent coronary angiography,
      left main trunk (LMT) was externally compressed only at diastolic phase, showing
      acute type A aortic dissection involving the left coronary artery. A bare metal
      stent was promptly implanted to LMT to restore coronary blood flow because of her
      hemodynamic instability. Soon after this procedure, ischemic changes disappeared
      on ECG and she was transferred to the operating room in stable hemodynamic
      condition without chest discomfort. Emergent graft replacement of ascending aorta
      and proximal portion of transverse arch was successfully performed. As the bare
      metal stent had been properly implanted at the LMT and weaning from
      cardiopulmonary bypass was uneventful regardless of decreased left ventricular
      wall motion of anteroseptal area, coronary artery bypass grafting was not
      performed. A "bridge to surgery" use of coronary stenting was very effective as a
      life saving procedure for the patients with acute aortic dissection involving the
      left coronary artery.

PMID- 21842674
TI  - [Reoperation of Blalock-Taussig shunt for double outlet right ventricle and
      pulmonary atresia in an adult].
AB  - A 36-year-old man was admitted to our hospital due to dyspnea and pneumonia. He
      had undergone left classical Blalock-Taussig shunt at 5 years old and right
      modified Blalock-Taussig shunt at 16 years old, because he was judged as no
      indication for any radical operation. Since the last surgery, he had stopped
      visiting hospital. Computed tomography showed pneumonia and pulmonary embolism in
      the left lower lung and occlusion of the right modified Blalock-Taussig shunt.
      After pneumonia was improved by antibiotic treatment, he underwent reoperation of
      the right modified Blalock-Taussig shunt using 8 mm knitted Dacron graft.
      Postoperative course was uneventful and dyspnea and cyanosys were improved. We
      successfully treated a complicated case of an adult congenital heart disease by
      reoperation of the right modified Blalock-Taussig shunt.

PMID- 21842675
TI  - [Diaphragmatic metastasis from uterine corpus cancer].
AB  - We report a case of metastatic diaphragm tumor from uterine corpus cancer. A 72
      year-old female had a tumor on right diaphragm 4-years after operation for
      uterine corpus cancer. After chemotherapy, tumor resection was performed by right
      lung basal segmentectomy, partial liver resection, and partial diaphragm
      resection. The pathological examination revealed adenocarcinoma, compatible with
      uterine corpus cancer, metastasizing in diaphragm and involving lung and liver.
      After the operation, a local recurrence occurred at parasternal lymph node, which
      is considered to be present on the efferent route of lymph flow from diaphragm.

PMID- 21842676
TI  - [Adult Bochdalek hernia combined with pneumothorax].
AB  - A 71-year-old man, who had been given a diagnosis of Bochdalek hernia in infancy,
      was referred to our hospital for dyspnea The chest X-ray and computed tomography
      (CT) showed left pneumothorax with bullas and intestines in his left thoracic
      cavity. He was admitted to our hospital and a chest tube was inserted into the
      left pleural cavity. The left lung expanded immediately and air leakage was
      stopped. He became asymptomatic and he was discharged from the hospital on the
      8th day. Most Bochdalek hernias are observed in infancy, and adult cases combined
      with pneumothorax and bullas are very rare.

PMID- 21842677
TI  - [Mitral regurgitation with concomitant atrial septal aneurysm; report of a case].
AB  - A 64-year-old female was admitted to our hospital because of severe dyspnea.
      Echocardiography revealed mitral valve regurgitation and atrial septal aneurysm
      (ASA). After instituting medical treatment for congestive heart failure,
      euvolemic status was achieved, and the patient underwent; (1) prosthetic patch
      repair for ASA; (2) mitral valvuloplasty with partial quadrangular resection of
      the posterior mitral leaflet; and (3) mitral annuloplasty using Physio ring.
      Pathological examination revealed myxomatous degeneration of the mitral valve,
      but the resected atrial septum was without any abnormality. ASA can lead to
      cerebral or pulmonary embolism even in the absence of an atrial septal defect.
      However, ASA without atrial septal defect is typically asymptomatic and rarely
      requires surgical correction. By contrast, ASA with concomitant mitral valve
      prolapse is associated with a high risk of cerebral or pulmonary embolism.
      Aspirin therapy is indicated for the prevention of thromboembolism in patients
      with ASA who do not undergo surgical management, and these patients also require
      careful observation.

PMID- 21842678
TI  - [Isolated infective endocarditis located in the tricuspid valve; report of a
      case].
AB  - We report surgically treated case of tricuspid valve endocarditis in a non-drug
      addict. A 74-year-old man with no history of cardiac disease was admitted to our
      hospital for persistent pyrexia. The blood culture was negative. Echocardiography
      showed vegetations attached to the tricuspid valve with mild tricuspid
      regurgitation. Intravenous antibiotics therapy was unable to control the
      infection. So we performed tricuspid valve repair and annuloplasty using an
      artificial ring. The postoperative course was uneventful. After prophylactic
      antibiotic administration for 15 weeks, he was afebrile for 1 week without any
      medication. Thereafter he was discharged and has been free from any complication
      for over 16 months.

PMID- 21842679
TI  - [Primary lung cancer with pulmonary hypertrophic osteoarthropathy mimicking bone
      metastasis; report of a case].
AB  - A 64-year-old man visited our hospital, due to right shoulder pain and fever.
      Chest X-ray revealed a well-defined tumor in the upper field of the left lung,
      and the histological diagnosis was adenocarcinoma. Bone scintigraphy demonstrated
      abnormal accumulation localized in the right shoulder joints. Although bone
      metastasis was highly suspected, pulmonary resection was performed to remove
      infected pulmonary tumor. A week after pulmonary resection, his shoulder pain
      dramatically improved, and abnormal accumulation in bone scan decreased
      definitely 1 month later. In conclusions, this is an atypical case of
      hypertrophic osteoarthropathy accompanying lung cancer.

PMID- 21842680
TI  - [Surgery for pulmonary actinomycosis that was difficult to differentiate from
      lung cancer; report of a case].
AB  - We herein report a case of pulmonary actinomycosis that was difficult to
      differentiate from lung cancer. The patient was a 53-year-old man who visited our
      hospital with a chief complaint of bloody sputum. Computed tomography (CT) showed
      a tumor in the anterior basal segment (S8) of the left lower lobe that contained
      a low density area, and because elevated C-reactive protein (CRP) was also
      observed, the patient was diagnosed with a lung abscess. As no improvements were
      seen after 4 months of antibiotic administration, and accumulation was observed
      at the same site on positron emission tomography (PET), the patient was diagnosed
      with lung cancer and underwent surgery. Following segmental resection, the
      patient was found to have pulmonary actinomycosis. It is necessary to consider
      pulmonary actinomycosis in patients with lung tumors.

PMID- 21842681
TI  - [Draft of guidelines for human body dissection for clinical anatomy education and
      research and commentary].
AB  - This article analyses the Draft of Guidelines for Human Body Dissection for
      Clinical Anatomy Education and Research drawn by the Study Group for Future
      Training Systems of Surgical Skills and Procedures established by the Fiscal Year
      2010 research program of the Ministry of Health, Labor and Welfare. The purpose
      of the Draft of Guidelines is: First, to lay out the required basic guidelines
      for human cadaver usage to allow medical and dental faculty to conduct clinical
      education and research in accordance with existing regulations. Second, the
      guidelines are expected to give physicians a regulatory framework to carry out
      cadaver training in accordance with the current legal framework. This article
      explains the Draft of Guidelines in detail, outlines the future of cadaver
      training, and describes issues which must still be solved.

PMID- 21842682
TI  - [Final report of the working group for the future planning of the Japanese
      Association of Anatomists].
AB  - The working group for the future planning of the Japanese Association of
      Anatomists (JAA) has been working to address the issues that were consulted from
      the president of JAA since October 2009. After making the interim report in March
      2010, a public hearing for general members of the JAA was held and a final report
      was submitted to the President in January 2011. The report contains the analysis
      of the current situation, the directions in which we should proceed, and
      recommendations of concrete actions that JAA should take for each issue. The
      issues discussed were as follows: 1. Future prospects of anatomy and
      morphological sciences. How can we maintain the specialties of morphological and
      anatomical sciences in the rapidly advancing field of life sciences and develop
      collaborations with other fields? 2. Improvement of the JAA academic meetings.
      How can we increase JAA members and young participants in the academic meetings
      of the JAA? 3. Fostering the next generation of young researchers. How can we
      increase young researchers graduated from the schools of Medicine or Dentistry?
      4. Future prospects of education of gross anatomy. Prospects of education in
      gross anatomy and the body donation registration system in relation with some new
      cadaver-related movements.

PMID- 21842683
TI  - [Examination of the inspiratory flow rates of COPD patients in Japanese medical
      facilities].
AB  - Chronic obstructive pulmonary disease (COPD) is treated primarily with inhalation
      therapy. However, as many COPD patients are elderly, whether or not patients
      inhale dry powder at an adequate inspiratory flow rate requires investigation. We
      therefore conducted a multicenter investigation of the effects of height, body
      weight, age, disease severity, and other factors on inspiratory flow rate in COPD
      patients. METHODS: We measured inspiratory flow rates and forced expiratory
      volume in the first second (FEV1) with the In-Check Dial (Clement Clarke) fitted
      with a discus adapter in 175 COPD patients of 40 years old and over (mean age
      71.3, men 89.1%, women 10.9%). RESULTS: A total of 98.9% of the patients had an
      inspiratory flow rate exceeding 30L/minute. Two patients had a rate of 30L/minute
      or less. The mean inspiratory flow rate was 98 +/- 30L/minute overall, 104 +/-
      27L/minute in mild COPD, 109 +/- 28L/minute in moderate COPD, 91 +/- 26L/minute
      in severe COPD, 71 +/- 24L/minute in very severe COPD, and 83 +/- 28L/minute in
      patients 75 years and older. Inspiratory flow rates significantly correlated with
      body mass index and FEV1. CONCLUSION: Most elderly patients with COPD maintained
      a sufficient inspiratory flow rate when inhaling dry powder.

PMID- 21842684
TI  - [Inconsistency in the A-DROP system of the JRS guidelines for the management of
      community-acquired pneumonia and its outcome in adults].
AB  - We evaluated the consistency of the A-DROP system for community-acquired
      pneumonia (CAP) and its outcomes, and developed a new severity classification of
      community-acquired pneumonia using nonlinear discriminant analysis. A total of
      615 patients with CAP were enrolled between 2004 and 2009. A poor outcome was
      defined as patients requiring ventilation and/or death from CAP. We investigated
      the influence of prognostic factors on CAP severity and outcome using a logistic
      regression model to obtain the coefficient, and a contingency table. The optimal
      cutoff points for age and BUN were calculated from receiver-operating
      characteristic (ROC) curves. The influence of respiratory failure was
      approximately twice that of other prognostic factors. The optimal cutoff point
      for age was 83 years old, and that for BUN was 23mg/dl. We found inconsistencies
      in the equivalence of all prognostic factors and the addition-scoring method in
      predicting outcome. To ensure consistency between the A-DROP system and outcome,
      we believe that the weight of respiratory failure, threshold of classification,
      and cutoff points for age and BUN should be revised.

PMID- 21842685
TI  - [Successful treatment of invasive pulmonary aspergillosis with a fungus ball and
      infiltration by the long-term administration of liposomal amphotericin B].
AB  - A 64-year-old diabetic man was admitted because his general condition had not
      improved despite the admini stration of voriconazole in another hospital, and his
      condition had become critical. Chest CT demonstrated a large fungus ball and
      consolidation around a cavity in the right lung. Aspergillusfumigatus was
      detected on a sputum culture. Based on these findings, we diagnosed invasive
      aspergillosis and administered high-dose (5mg/kg) liposomal amphotericin B (L
      AMB) for 8 weeks, which resulted in the improvement of his general condition and
      the disappearance of the fungus ball, without severe adverse events.

PMID- 21842686
TI  - [A case of lung cancer with endometrial metastasis].
AB  - A 50-year-old woman was admitted because of chest pain and lumbago. A chest X-ray
      film showed a 4-cm mass in the left lower lung field. Computed tomography scans
      revealed a nodule with spicule formation in the left lower lobe, and therefore we
      strongly suspected lung cancer. Fiberoptic bronchoscopy yielded a diagnosis of
      adenocarcinoma. However, since she had metrorrhagia we performed an endometrial
      biopsy. Histologically, the endometrium was similar to the lung lesion, with
      positive staining for thyroid transcription factor-1 (TTF-1), and lung cancer
      with endometrial metastasis was therefore diagnosed. Although lung cancer with
      endometrial metastasis is rare, it should be included in the differential
      diagnosis in patients with gynecological symptoms such as metrorrhagia.

PMID- 21842687
TI  - [A case of alveolar hemorrhage caused by gefitinib].
AB  - Although drug-induced interstitial pneumonitis caused by gefitinib is well
      recognized in Japan, reports of alveolar hemorrhage caused by gefitinib are very
      rare. We encountered a case of alveolar hemorrhage thought to be caused by
      gefitinib. A 74-year-old woman with non-small cell lung cancer (adenocarcinoma;
      cT4NOM0, stage IIIB) had been receiving gefitinib as second-line therapy from
      January 2009. However, bloody sputum and nasal bleeding were observed 2 weeks
      after the initiation of gefitinib therapy. Chest radiography and computed
      tomography revealed ground-glass opacities predominantly in the lower lung
      fields. Bronchoscopy was performed, and the bronchoalveolar lavage fluid obtained
      from the right B8 was bloody. Her symptoms and chest ground-glass opacities
      improved after the withdrawal of gefitinib. Based on these clinical findings, we
      diagnosed alveolar hemorrhage caused by gefitinib. If chest radiography or
      computed tomography findings of gefitinib-treated patients show ground-glass
      opacities, the possibility of not only interstitial pneumonitis, but also
      alveolar hemorrhage should be considered in the differential diagnosis.

PMID- 21842688
TI  - [Two cases of type I respiratory failure managed by the highFO nebulizer].
AB  - Among conventional oxygen therapies there are currently no devices which can
      supply a high oxygen level of over 60%. The HighFO nebulizer (Koike Medical) is a
      new device which is able to supply an oxygen flow rate of over 35l/min, and a
      high concentration of oxygen. We report 2 cases of type I respiratory failure
      managed by the HighFO nebulizer. Case 1: A 70-year-old man with lung cancer had
      an acute exacerbation of radiation pneumonitis during chemoradiotherapy. We gave
      him an oxygen mask with a reserve bag, but his condition worsened. We then used
      the HighFO nebulizer followed by non-invasive positive pressure ventilation. He
      began to recover and we again used the HighFO nebulizer during the weaning
      period. Case 2: A 74-year-old man presented with acute exacerbation of
      interstitial pneumonitis. We started steroid pulse therapy, HighFO nebulizer
      treatment and physiotherapy to prevent disuse syndrome. We were able to raise his
      exercise stress levels due to the high concentration of oxygen provided by the
      HighFO nebulizer. We believe that the HighFO nebulizer is useful for type-I
      respiratory failure as well as interstitial pneumonia. However, oxygen toxicity
      is a potential problem, so we must accumulate more cases in order to fully assess
      the risks and benefits of this new modality.

PMID- 21842689
TI  - [A case of small cell lung cancer that presented with paraneoplastic syndrome].
AB  - A 65-year-old man had suffered from systemic erythema from November 2008 and had
      noticed gradually progressing weakness in the upper and lower limbs. He received
      medical treatment in another hospital but his symptoms did not improve. He was
      admitted to our hospital for treatment of diabetes in June 2009, and his chest X
      ray images and CT scans showed a mass shadow in the right upper lobe with hilar
      and mediastinal lymphadenopathy. We performed bronchoscopy, and diagnosed small
      cell lung cancer (T2N2M1, stage IV). However, he had hand grip weakness and
      continuing upper and lower limb muscle weakness, and therefore electromyography
      was performed, which showed the presence of waxing in the right leg.
      Subsequently, a diagnosis of Lambert-Eaton myasthenic syndrome was made. As he
      also showed ataxia of the left lower extremity, we also diagnosed paraneoplastic
      cerebellar degeneration. We gave the patient chemotherapy consisting of
      carboplatin and etoposide which resulted in the disappearance of his waxing, and
      his grip strength and erythema immediately improved with regression of the tumor
      after 1 course of chemotherapy. We report a case of small cell lung cancer
      associated with Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar
      degeneration and erythema which presented as paraneoplastic syndrome, which
      improved with chemotherapy.

PMID- 21842690
TI  - [A case of valsartan-induced pneumonitis with marked elevation of serum KL-6].
AB  - A 64-year-old man, who had been treated with valsartan for hypertension since
      about 2 months previously, was admitted with exertional dyspnea. A chest X-ray
      film on admission showed infiltrative shadows in bilateral lower lung fields.
      Chest computed tomographic images showed diffuse ground-glass opacities,
      consolidation and traction bronchiectasis. His serum KL-6 level was markedly
      elevated, to 7,360 U/ml. Despite the withdrawal of valsartan, his symptoms
      deteriorated, and a drug lymphocyte stimulation test was positive for valsartan.
      Based on these findings, we diagnosed valsartan-induced pneumonitis.
      Glucocorticoids were administered, and his symptoms, chest radiograph findings
      and serum KL-6 level all improved. Currently, angiotensin II receptor blockers
      (ARBs), including valsartan, are often used as the first drug of choice to treat
      hypertension, but they can cause drug-induced pneumonitis. It has been previously
      reported that serum KL-6 levels may reflect the clinical activity of drug-induced
      pneumonitis. In cases of drug-induced pneumonitis with a high level of serum KL
      6, glucocorticolds should be started at an early stage.

PMID- 21842691
TI  - [An elderly case of anomalous systemic arterial supply to the normal basal
      segment of the left lower lobe and summary of reports of the disease in Japan].
AB  - A 69-year-old asymptomatic woman was admitted because of an abnormal chest
      shadow. Chest X-ray films showed a tumorous shadow behind the heart. Chest CT
      scans showed an aberrant artery branching from the thoracic aorta and supplying
      the left basal segment, but the bronchial tree was normal. The left lung vein was
      normal but wide, and the left lower pulmonary artery could not be observed. Based
      on these findings, we diagnosed anomalous systemic arterial supply to the normal
      basal segment of the left lower lobe. Because this patient had a high risk of
      heart failure and pulmonary hypertension, we decided to perform a left lower
      lobectomy, but she refused the operation. As this disease is generally found in
      younger patients, diagnosis in older age, as in the present case, is rare. In
      this report we also summarize 39 other reports of this disease in Japan.

PMID- 21842692
TI  - [A brain abscess as a complication of hepatopulmonary syndrome coexisting with
      interstitial pneumonia].
AB  - A 76-year-old woman with a 20-year history of chronic hepatitis C was referred to
      our hospital for worsening exertional dyspnea. She had been given a diagnosis of
      interstitial pneumonia based on chest computed tomography findings 5 years
      previously. Contrast-enhanced echocardiography confirmed an intrapulmonary right
      to-left shunt, and therefore we diagnosed hepatopulmonary syndrome comorbid with
      interstitial pneumonia. In July 2009 she was admitted to our hospital with a low
      grade fever, headache, and vomiting. We diagnosed a left cerebellar brain abscess
      caused by Streptococcus intermedius. She underwent stereotactic burr-hole
      drainage and received vancomycin, piperacillin and cefotaxime. Cases of brain
      abscess secondary to hepatopulmonary syndrome are rare. Nevertheless, we should
      be aware of this complication of hepatopulmonary syndrome.

PMID- 21842693
TI  - [Two cases of drug-induced intrathoracic lesions caused by mesalazine in patients
      with ulcerative colitis].
AB  - We encountered 2 cases of drug-induced intrathoracic lesions caused by allergic
      reactions to mesalazine in patients with ulcerative colitis. Case 1: A 26-year
      old man had a fever, cough and exertional dyspnea after 1 month of mesalazine
      treatment. He was hospitalized because of bilateral pulmonary infiltrates on a
      chest X-ray film. Case 2: A 27-year-old woman complained of fever and left back
      pain that exacerbated after 2 weeks of mesalazine treatment. She was hospitalized
      because of bilateral pulmonary effusions on chest CT. Both patients showed a
      positive reaction to a drug lymphocyte stimulation tests (DLST) for mesalazine.
      The first case was given a diagnosis of eosinophilic pneumonia by bronchoscopic
      examination, and responded to steroid therapy after discontinuation of
      mesalazine. The second case was given a diagnosis of pleuritis and improved on
      cessation of Mesalazine treatment.

PMID- 21842694
TI  - [A case of Sjogren syndrome coexistent with MALT lymphoma occurring along the
      parotid gland and trachea].
AB  - A 62-year-old woman with Sjogren syndrome was admitted for computed tomographic
      (CT) evaluation of a thickened trachea and parotid tumor. She had been given a
      diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma 6 years
      previously, and had undergone surgical resection of the parotid tumor. Endoscopic
      examination revealed an annular tumor that had formed a stricture in the mid
      trachea. Pathologic specimens were obtained by surgical resection of the parotid
      tumor and bronchoscopic biopsy of the tracheal tumor. Both histological
      examinations revealed MALT-type marginal zone B-cell lymphoma. Because CD20
      immunostaining was positive, the patient received 6 cycles of rituximab plus
      cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) without any
      signs of major toxicity. All lesions disappeared after treatment, and this
      patient remained disease-free for 40 months.

PMID- 21842695
TI  - [A case of miliary tuberculosis showing diffuse alveolar hemorrhage].
AB  - A 43-year-old diabetic man had a productive cough and high fever and was admitted
      to another hospital. His condition did not improve despite treatment with
      Cefepime, and he was transferred to our hospital. Chest X-ray films and CT
      findings showed pulmonary infiltration and diffuse ground-glass opacities in
      bilateral lung fields, but disseminated nodules were not identified. Since his
      bronchial lavage fluid (BALF) was bloody, we suspected diffuse alveolar
      hemorrhage due to vasculitis. Steroid pulse therapy was given, and his fever and
      chest X-ray findings completely improved. However, 1 week later, he again
      suffered a high fever and bloody sputum, and a chest X-ray film showed granular
      shadows in bilateral lung fields. He died of respiratory failure on the 18th
      hospital day despite treatment and mechanical ventilation. An autopsy revealed
      many necrotizing epithelioid granulomas in both lungs, the liver, the spleen,
      both kidneys and both adrenal glands. These findings indicated miliary
      tuberculosis, and a culture of his sputum and BALF finally revealed mycobacterium
      tuberculosis. Marked alveolar hemorrhage and a hyaline membrane were also found
      in both lungs, but vasculitis was not recognized in any organ. We report this
      case, because to the best of our knowledge diffuse alveolar hemorrhage has not
      been reported as the primary symptom of miliary tuberculosis.

PMID- 21842696
TI  - [A case of pulmonary alveolar proteinosis presenting with miniscule ground-glass
      opacity in the apex of the left lung].
AB  - A 66-year-old man was found to have a very small ground-glass opacity in the apex
      of the left lung. Because the ground-glass opacity had slightly enlarged after 2
      years, video-assisted thoracic surgery (VATS) biopsy was performed. The
      histological findings showed the alveolar spaces to be filled with PAS-positive
      granular materials, so pulmonary alveolar proteinosis was diagnosed. Although his
      bronchoalveolar lavage fluid (BALF) did not have a milky appearance, his serum
      and BALF GM-CSF autoantibody and serum KL-6 levels were elevated. Asymptomatic
      pulmonary alveolar proteinosis may appear as very small ground-grass opacities.

PMID- 21842697
TI  - Lymphoma classification: the quiet after the storm.
AB  - The classification of malignant lymphomas remained controversial for over 30
      years. The first scheme was proposed by Rappaport in the '60th and was based on
      incorrect histogenetic concepts. To overcome these limitations, several groups
      formulated new proposals in '70th. Among these two merited attention: the Lukes
      and Collins and the Kiel Classifications. They were based on the assumption that
      each lymphoma category might be related to a precise differentiation step of the
      lymphoid system, thus excluding any correlation with histiocytes, present on the
      Rappaport scheme. The Kiel Classification became very popular in Europe, while
      the one of Luke and Collins did not meet success in the United States (U.S.). In
      1978, the National Cancer Institute proposed an international trial to compare
      the classifications used in Europe and U.S. The result was the genesis of the
      Working formulation, the tool for lymphoma classification in the U.S. up to the
      early '90th, but which was conversely rejected in Europe. In order to get over
      this lack of transatlantic communication, in 1994 the Revised European-American
      Lymphoma (REAL) Classification was proposed by the International Lymphoma Study
      Group. Its goal was to list "real" entities, each defined by the presence of
      homogeneous morphologic, phenotypic, cytogenetic, molecular, and clinical
      criteria, along with the possible recognition of its normal counterpart. The REAL
      Classification became the model for the WHO Classification of all haematopoietic
      tumours published in 2001. The present review aims to analyse future perspectives
      after the fourth edition of the WHO Classification released in 2008.

PMID- 21842698
TI  - Pathobiology of acute lymphoblastic leukemia.
AB  - In the present review, the authors described the pathobiological features of B-
      and T-ALL, which appear to be quite heterogeneous with regard to molecular
      pathogenesis. The last edition of the World Health Organization Classification
      considered this aspect by defining many entities based on genetic findings. This
      approach is not only important for prognostic stratification, but also in the
      near future will surely represent the basis for the definition of patient
      specific therapeutic approaches. A striking example is Ph+ acute lymphoblastic
      leukemia (ALL), which until the advent of tyrosine kinase inhibitors (TKI) has
      been regarded as the most aggressive ALL. The use of imatinib, dasatinib, and
      possibly more recent inhibitors has dramatically changed the clinical scenario,
      offering new opportunities to patients, especially the elderly. Similarly, the
      use of FLT3 inhibitors in mixed lineage leukemia-positive cases, gamma-secretase
      inhibitors in T-ALL, novel TKI, and monoclonal antibodies may represent a
      successful approach in the future.

PMID- 21842699
TI  - Marginal zone lymphoma.
AB  - The term marginal zone lymphoma includes a collection of different diseases with
      some shared morphologic and pathogenic features, but distinctive clinical
      presentation, immunophenotype, molecular abnormalities, and treatment
      recommendations. This review describes the main features of splenic marginal zone
      lymphoma, nodal marginal zone lymphoma, and extranodal marginal zone lymphoma,
      mucosa-associated lymphoid tissue type.

PMID- 21842700
TI  - Pathobiology and diagnosis of follicular lymphoma.
AB  - Follicular lymphoma is one of the most frequent lymphomas in the western
      hemisphere. The diagnosis of this lymphoma is based primarily on morphology and
      immunohistochemistry. Although the basic diagnostic principles have been
      unchanged for decades, the concept of lymphoma pathogenesis and subtyping is
      still being developed. Most importantly, the grading of follicular lymphoma and
      the definition of transformation continue to be controversial. Early lesions of
      follicular lymphoma can be identified using immunohistochemistry, which presents
      a challenge to diagnostic histopathologists, but can by contrast help us to
      understand the pathogenesis of the disease. Histopathologists should be aware of
      variants of this lymphoma that present with specific histologic and clinical
      features, such as pediatric follicular lymphoma.

PMID- 21842701
TI  - Chronic lymphocytic leukemia: the pathologist's view of lymph node
      microenvironment.
AB  - Chronic lymphocytic leukemia (CLL), an indolent B-cell malignancy frequently
      diagnosed in the elderly, is characterized by the relentless accumulation of CD5+
      monoclonal B cells that proliferate in the appropriate tissue microenvironments.
      Despite many advances achieved by molecular and functional studies, our knowledge
      of the reciprocal relationship between the CLL cell and its microenvironment at
      the tissue level is still largely incomplete. In this review we present the
      relevant current information on the tissue microenvironmental features of CLL,
      focusing on the events that appear to occur in the lymph node. Special attention
      is devoted to analyzing the properties of both neoplastic and nonneoplastic
      bystander cells within proliferation centers, the mysterious structures that
      likely represent the actual proliferative compartment.

PMID- 21842703
TI  - Infectious agents and lymphoma.
AB  - In the past 25 years revelations on the genesis of human cancer have come at an
      increasing pace. Research on oncogenic infectious agents, especially viruses, has
      helped us to understand the process of malignant transformation of cells because
      the cellular events in viral-driven transformation mirror, often brilliantly,
      basic cellular processes that culminate in cancer, even those not associated with
      viruses. Infectious agents, especially viruses, account for several of the most
      common malignancies-up to 20% of all cancers. Some of these cancers are endemic,
      with a high incidence in certain geographic locations, but sporadic/lower
      incidence in other parts of the world. Lymphomas arise frequently in association
      with infectious agents such as Epstein-Barr virus, human immunodeficiency virus,
      human herpes virus 8, Helicobacter pylori, and hepatitis C virus. In this review,
      we will focus on the association between infectious agents and lymphomas, with a
      look at the molecular mechanisms they use to disturb cell regulation and
      eventually result in cancer.

PMID- 21842702
TI  - Molecular pathogenesis of diffuse large B-cell lymphoma.
AB  - In past years, substantial insight regarding the pathogenesis of diffuse large B
      cell lymphoma has been obtained. Particularly, based on gene expression profile
      analysis, this disease can be classified into distinct phenotypic subgroups and
      specific transcriptional programs have been identified. New technologies like
      next-generation whole genome/exome sequencing and genome-wide single nucleotide
      polymorphism array analysis have revealed novel lesions involved in the
      pathogenesis of this disease. This review focuses on the diversity of genetic
      lesions identified in the different subtypes of diffuse large B-cell lymphoma.

PMID- 21842704
TI  - Booster hepatitis B vaccination not necessary for long-term protection in
      children immunised with hexavalent vaccines.

PMID- 21842705
TI  - Determinants of invasiveness and ability to cause invasive pneumococcal disease,
      pneumonia and acute otitis media of different serotypes of Streptococcus
      pneumoniae.

PMID- 21842706
TI  - Hospital acquired infections in a large north Ugandan hospital.
AB  - INTRODUCTION: Hospital care is a precious gift in Uganda, therefore little
      concern is given to hospital safety and very seldom Hospital Acquired Infection
      (HAI) risk is evaluated. Within a quality improvement hospital program the Board
      of Lacor Hospital, a large Missionary Hospital of north Uganda, ordered an HAI
      control program to be established. The first step of this program was an HAI
      prevalence survey whose results are presented in this paper. METHODS: A one day
      prevalence survey was performed on patients admitted at least 48 hours before the
      survey: short training was offered to qualified nurses and hospital doctors.
      Lacking a suitable microbiological diagnostic service, clinical definitions of
      HAI were adopted. Questionnaires were completed by the nurses and data were
      analyzed and presented to the hospital personnel four days after the survey. A
      HAI control program was agreed and started soon after. RESULTS: The hospital has
      44.000 admissions yearly with 482 beds and main hospital specialties, 410
      patients were surveyed Overall HAI prevalence was 28%, more in surgery (47%) and
      less in pediatrics (21%). Blood stream infections were the most frequent,
      followed by surgical wound infections and Urinary Tract infections, several lower
      respiratory tract infections and few gastrointestinal one. HAI prevalence was
      associated with length of stay in hospital, intravenous cannulas, urinary
      catheters and emergency surgery. Patients with severe low nutrition status,
      anemia and complications of the main disease bringing them to hospital
      experienced higher HAI prevalence. DISCUSSION: This paper shows that HAI can be
      measured also in absence of microbiological service and that Hospital staff are
      ready to evaluate this problem. This high HAI prevalence was not expected by the
      staff and has been a starting point for an hospital HAI control plan.

PMID- 21842707
TI  - @Prevention: a website project for prevention in the healthcare setting.
AB  - In the field of prevention, Internet websites and their related instruments
      constitute valuable tools for healthcare facilities, and particularly for Local
      Healthcare Authorities (LHA). As yet, however, their undoubted potential remains
      largely unexploited. Many LHA websites currently operating in Italy are organized
      in such a way that they fail to make adequate use of this precious resource.
      Indeed, communication regarding prevention is all too often limited to the simple
      reproduction of information and indications in a static and heterogeneous manner,
      so much so that it resembles a mere "online notice-board". The aim of the present
      research was to analyze the current situation and the various innovative
      proposals that have been made, in order to construct a more effective website
      model that could be used nationwide. To this end, the research was carried out
      through a two-pronged approach: on the one hand, all 190 LHA websites in Italy
      were analyzed; on the other, a questionnaire was administered to a sample of
      habitual users of the most modern and widespread social network, Facebook.
      Analysis and elaboration of the data gathered led to the creation of the model
      "@Prevention". This project is intended to introduce an innovative perspective
      into the field of online communication for healthcare prevention by providing a
      highly useful tool for the LHA, healthcare workers and, obviously, citizens.

PMID- 21842708
TI  - Knowledge and attitudes about vaccinations among adolescents.
AB  - PURPOSE: The aim of this study was to investigate among adolescents in Antwerp
      their knowledge about vaccination and to describe their information sources,
      motives and barriers for vaccination. METHODS: In March 2009, adolescents aged
      between 14 and 17 years from three schools with a mixed Belgian and immigrant
      population in Antwerp completed a written questionnaire concerning vaccination.
      The questionnaire was already used and validated in a study in five European
      countries: France, Italy, Spain, Germany and the United Kingdom. RESULTS: In
      total 186 adolescents completed the questionnaire. Most of them (93%) knew that
      vaccination is a method to prevent disease. Most adolescents knew about the
      existence of vaccines against tetanus (94%), hepatitis B (91%) and human
      papillomavirus (87%). The most important sources for information were the family
      physician (83%), the school (79%) and the parents (70%). Their knowledge about
      vaccinations was not related to courses about vaccination at school. CONCLUSIONS:
      The physician, the school and the parents play a key role in the vaccination of
      adolescents. Our results are in many aspects similar to those in the other
      European countries.

PMID- 21842709
TI  - Holistic model-based monitoring of the human health status in an urban
      environment system: pilot study in Verona city, Italy.
AB  - INTRODUCTION: In recent decades the global health paradigm gained an increasing
      systemic characterization. The ecosystem health theory states that a healthy
      ecosystem, whether natural or artificial, significantly contributes to the good
      health status of the human population. METHODS: The present study describes an
      interdisciplinary monitoring model that retrospectively analyzes the intersection
      between the urban environment and citizens. The model analyzes both the
      biophysical and the anthropic subsystems through the application of landscape
      ecology and environmental quality indexes along with human health indicators.
      Particularly, ecological quality of landscape pattern, atmospheric pollution,
      outdoor noise levels and local health indicators were assessed. Verona
      municipality was chosen as study area to test the preliminary efficiency of the
      model. Territory was split into two superimposed layers of land units, which were
      further geo-referentiated with Geographical Information System (GIS) technology.
      Interdependence of any of the analyzed traits was further investigated with
      Fisher exact test. RESULTS: Landscape composition was assessed and an Average
      Ecological Quality (AEQ) score assigned to each land unit. A direct
      proportionality emerged for concentrations of considered air pollutants and
      traffic levels: a spatial model for the atmospheric pollution was drawn. A map
      depicting the distribution of traffic-related noise levels was also drawn. From
      chosen indicators, a quality class score was assigned to every minor and major
      land unit. Age-standardised rates about hospitalizations for the municipal
      population and specific rates for the over-65s/1000 inhabitants were calculated.
      Quality class assignement for each health indicator was graphically rendered.
      After direct standardisation of rates for the population sample, data were
      compared with two reference populations, the Regional population and the Local
      Socio-sanitary Unit (ULSS20) population. Standardised hospitalization rates for
      the whole municipal population always resulted lower than the ULSS20 rates,
      except for auditory pathologies. It was notable that rates of hospitalizations
      for cancerous diseases for Verona municipal population were four times and two
      times lower than the ULSS20 and the Regional population ones, respectively.
      Contingency table were made for the health main indicator (specific rates for the
      over-65s/1000 inhabitants) and the environmental quality key factors of landscape
      ecological quality, outdoor noise level and air pollution. H0 of independence was
      rejected for respiratory pathologies and air pollution and for the triad
      cardiocirculatory pathologies, air pollution and landscape ecological quality at
      (a = 0.05). Fisher exact test confirmed the non-independence of cardiocirculatory
      diseases and biophysical environment and the analogous association for
      respiratory pathologies when comparison was made with global environmental
      quality index. DISCUSSION: The first testing of the model suggests some possible
      elements of implementation and integration which could further enhance it. Among
      them, the subjective investigation of the health status assumes a primary role.
      On the whole the monitoring model seems to effectively represent the real
      complexity of the urban environment systems and should be regarded as an
      important contribution to the new way of health research.

PMID- 21842710
TI  - Comparison of environmental health status in primary schools in different
      districts of Isfahan city in 2008-2009.
AB  - INTRODUCTION: Students spend at least 20% of their time in schools. Training,
      educating and the personality of these students depends on appropriate
      educational methods, proper physical space, and also favorable mental
      environment. Students are considered as a major human resources of any society
      and dealing with their health and promoting educational environment health is in
      fact a kind of investment for future. In this study we examined the status of
      environmental health status in primary school of different districts of Isfahan.
      MATERIALS AND METHODS: This study was a descriptive-analytical study. The number
      of studied samples was 77 schools in Isfahan which were selected by regular
      randomized method The tool used to gather data was a environmental health inquiry
      form for school environments, and consisted of two parts: the first part included
      common school specifications and the second part involved items dealing with
      desirability of various parts of schools.The above forms were filled out in 3
      months by specialists in public health, evaluating the schools and interviewing
      the principals. Then, they were analyzed and a comparison was made between the
      results from various districts. RESULTS: 76.6% of schools complied with the
      standards and 80.5% of classrooms were in desired conditions. Regarding the
      standards for building and classrooms, there was no significant difference
      between various districts. Hygiene services (water closets and basin) and
      drinking water were at desired level and there was no significant difference
      between various districts in this regard, however the district 1 was in undesired
      condition. Regarding collecting and disposing of rubbishes and trashes, 79% of
      schools were in desired condition and 49% of them had hygienic tuck-shops
      according to standards, but there was no significant difference between various
      districts. CONCLUSION: The study showed that the status of environment health is
      at desired level in primary schools in Isfahan, but the health of tuck-shops
      should improve in schools and it needs more attention and interest from
      authorities of Ministry of Education and Ministry of Health and dedicating proper
      budgets to solve their health problems.

PMID- 21842711
TI  - Dance for your health.

PMID- 21842712
TI  - CMS changes telemedicine credentialing rules.

PMID- 21842713
TI  - IT: more than a tool for quality improvement.

PMID- 21842714
TI  - Data collection comes to palliative care.

PMID- 21842715
TI  - RACE program dashes to success.

PMID- 21842716
TI  - Getting a handle on glucose control.

PMID- 21842717
TI  - B cell toll-like receptors with respect to the pathogenesis of Sjogren's
      syndrome.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune immunopathological disease of
      unknown aetiology. It is characterized by focal lymphocyte infiltration and
      inflammation in exocrinne glands, involving especially salivary and lacrimal
      glands. Hypofunction of the glands leads to the decreased glandular secretion
      together with impaired production of saliva and tears, resulting in dryness of
      the mouth and eyes (xerostomia and xerophthalmia, respectively). Some of the
      studies have suggested that Toll-like receptors and B cells play a pivotal role
      in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus,
      rheumatoid arthritis and SS etc. Stimulation of B cells via the TLRs pathway
      leads to several important changes including increase in antibody production,
      differentiation to plasma cells, cytokine production and up-regulation of
      molecules essential for antigen presentation to (autoreactive) T cells.
      Experimental data support the idea that co-engagement of BCR and TLR might be
      sufficient for B cell activation and lead to the failure of tolerance. In human
      naive B cells, most TLRs are expressed at very low or undetectable level, but
      expression of TLR 7 and 9 is rapidly induced by B cell receptor triggering. This
      review will focus on the possible role of B cells and TLRs signaling in the
      pathogenesis of SS.

PMID- 21842718
TI  - Serum level of a soluble form of endoglin (CD105) is decreased after Goeckerman's
      therapy of psoriasis.
AB  - BACKGROUND: Goeckerman's therapy (GT) of psoriasis is based on daily application
      of pharmacy grade coal tar on affected skin with subsequent exposure to UV light.
      Disturbances in angiogenic activity are characteristic for the immunopathogenesis
      of psoriasis. The aim of study was to evaluate the influence of GT of psoriasis
      on proinflammatory and angiogenic activities expressed as changes in levels of
      endoglin (CD105). METHODS: Serum levels of a soluble form of endoglin were
      measured in peripheral blood samples of 38 patients with psoriasis before and
      after therapy. Sixty three otherwise healthy blood donors serve as a control
      group. The efficacy of GT was expressed as changes in Psoriasis Area and Severity
      Index (PASI). RESULTS: PASI score was significantly diminished by GT (p < 0.001).
      Serum levels of soluble CD105 were significantly diminished after GT. The serum
      level of soluble CD105 dropped from 7.85 +/- 2.26 ng/ml before therapy to 7.01 +/
      1.71 ng/ml after therapy (p = 0.0002). Compared to serum levels of soluble CD105
      in healthy blood donors, serum levels of soluble CD105 in patients before GT were
      significantly higher (p < 0.001) and remained elevated after therapy (p < 0.001).
      Angiogenic activity expressed as serum endoglin is diminished in patients with
      psoriasis treated by GT.

PMID- 21842719
TI  - The ameliorating effect of exogenous melatonin on urinary bladder function in
      hyperosmolar bladder overactivity and its influence on the autonomic nervous
      system activity.
AB  - This study was designed to investigate the effects of melatonin on the bladder
      hyperactivity in hyperosmolar-induced overactive bladder (OAB) rats.
      Additionally, the influence of melatonin on the autonomic nervous system (ANS)
      using heart rate variability (HRV) analysis was assessed. 40 rats were divided
      into four groups: I--control (n = 12), II--rats with hyperosmolar OAB (n = 6),
      III--rats with melatonin pretreatment and hyperosmolar OAB (n = 6) and IV-
      control with melatonin pretreatment (n = 6). In group III and IV melatonin in
      dose of 100 mg/kg was given. HRV measurements in 10 rats, as follow: control (n =
      2), control after melatonin treatment (n = 2), rats with hyperosmolar OAB without
      (n = 3), and after (n = 3) melatonin treatment were conducted. This study
      demonstrates marked influence of melatonin on urinary bladder activity in
      hyperosmolar-induced OAB rats. These rats showed significantly reduced the
      detrusor motor overactivity resulting in the improvement of cystometric
      parameters after melatonin treatment when compared to the control, as follow: a
      significant increase of intercontraction interval (70%) and functional bladder
      capacity (67%), as well as a decrease of the basal pressure, detrusor
      overactivity index and motility index of 96%, 439% and 40%, respectively. ANS
      activity analysis revealed sympathetic overactivity in OAB rats, and
      parasympathetic superiority in melatonin treated OAB rats. Melatonin treatment in
      rats with hyperosmolar OAB (group III) caused significant increase of nuHF
      parameter (from 51.00 +/- 25.29 to 76.97 +/- 17.43), as well as a decrease of
      nuLF parameter (from 49.01 +/- 25.26 to 23.03 +/- 17.43) and LF/HF ratio (from
      1.280 +/- 0.980 to 0.350 +/- 0.330). In conclusion, melatonin suppresses
      hyperosmolar OAB, and modulates ANS activity by inhibition of the sympathetic
      drive. Therefore, melatonin may become a useful agent for OAB management.

PMID- 21842720
TI  - Comparative outcomes of total knee arthroplasty on physically active and passive
      patients.
AB  - The physical activity of the population is decreasing due to an increase in
      sedentary lifestyles. The aim of the study was to analyze midterm results of
      total knee arthroplasty according to the lifelong physical activity of the
      patients. We evaluated 37 patients (23 women, 14 men), with age average 70.0
      years (range 53-87). We divided the patients according to lifelong physical
      activity. The active group included 11 patients with any history of physical
      activity and the passive included 26 patients with a sedentary lifestyle. No
      intergroup differences existed in age, gender or preoperative Knee Score. The
      active group had a higher postoperative Knee Score 90.5 (+/- 5.0) compared to the
      passive 87.4 (+/- 5.0). Pain after arthroplasty was experienced significantly
      more in the active group. Between the active 87.3 (+/- 9.3) and passive 67.5 (+/-
      16.7) groups we measured a statistically significant difference in the
      improvement of Functional Score - ability to walk and climb stairs. Sedentary
      lifestyle affects the clinical outcomes of total knee arthroplasty. This data is
      demonstrating that physical activity ameliorate functional postoperative results.

PMID- 21842721
TI  - Recovery from hypoxic pulmonary hypertension in rats.
AB  - To characterize the time frame of changes in pulmonary arterial pressure, right
      ventricular hypertrophy and morphology of small pulmonary arteries male Wistar
      rats were exposed to isobaric hypoxia (3 weeks, F1O2 0.1) and then let to recover
      on air for 1 or 5 weeks. Normoxic animals (group N) served as controls. Mean
      pulmonary arterial pressure (PAP), ratio of the weight of the right heart
      ventricle to the sum of the weights of the left ventricle and septum (RV/LV+S)
      and percentage of double laminated pulmonary vessels ( % DL) were measured at the
      end of hypoxic exposure (group H), after 1 or 5 weeks of recovery (groups 1R and
      5R), and in controls kept in air (group N). Three weeks in hypoxia resulted in
      increase in PAP, RV/LV+S and % DL. After 1 week of recovery RV/LV+S normalized,
      PAP decreased, while % DL did not change. After 5 weeks in air PAP returned to
      control values and % DL diminished significantly but did not normalize. Our
      results suggest that recovery depends on the degree of HPH and that knowledge of
      the time-frame of recovery is important for future studies in our rat model.

PMID- 21842722
TI  - Case 2-2011: cardiac amyloidosis.

PMID- 21842723
TI  - Scrotal mass: a rare complication of ventriculoperitoneal shunt.
AB  - SUMMARY: Ventriculoperitoneal shunts are associated with multiple complications.
      Among them are disconnection and migration of the tubing into the peritoneal
      cavity. Here we describe a case of a fractured ventriculoperitoneal shunt which
      migrated and coiled in the scrotum, masquerading as a scrotal swelling. Removal
      of the shunt via a scrotal incision was performed concomitantly with repair of
      the hernia sac.

PMID- 21842724
TI  - Nasal polyposis and fungal Schizophyllum commune infection: a case report.
AB  - We present a rare case of eosinophilic fungal rhinosinusitis with nasal polyps in
      a 32-year-old woman caused by basidiomycete fungus Schizophyllum commune.
      Diagnosis was done by the endoscopic nasal examination, computed tomography (CT)
      of the paranasal sinuses, the histopathological examination of polyps, the
      presence of eosinophils and fungal hyphae in nasal mucus and by the detection of
      S. commune by culture. The patient was successfully treated by combination of
      oral itraconazole and topical corticosteroid therapy combined with surgery. The
      pathogenesis and diagnosis of allergic fungal rhinosinusitis are also discussed.

PMID- 21842725
TI  - A delayed fatal metastatic Hurthle cell carcinoma.
AB  - Hurthle (oxyphilic or oncocytic) cell carcinoma is a variant of follicular cell
      carcinoma of thyroid. Although this entity of thyroid cancer is well known, its
      occurrence in young patients has scarcely been reported. We report a case of a 26
      year-old male patient, at the time of diagnosis, of Turkish origin, who developed
      a tracheal, pulmonary and mediastinal metastatic Hurthle cell carcinoma with
      bilateral cervical and mediastinal lymphadenopathies. This case illustrates an
      aggressive and metastatic cancer at the time of diagnosis and resistant to all
      treatment options including surgery, chemotherapy and radioactive iodine.

PMID- 21842726
TI  - Suicide attempt by swallowing sponge or pica disorder: a case report.
AB  - INTRODUCTION: There are many ways how children with mental illness have actually
      tried to hurt themselves. Suicidal thinking or attempts always indicate that
      professional help is needed (2). Every object which can be potential dangerous
      should be removed but this is very difficult to do. Some of children with these
      symptoms had Pica diseases. Pica is a medical disorder characterized by an
      appetite for substances largely non-nutritive (e.g. metal, coal, soil, feces,
      paper, soap, gum, etc.) or an abnormal appetite for some things that may be
      considered foods. MATERIAL AND METHODS: The patient swallow sponge from a pillow
      over a long period of time and she came into our hospital with abdominal pain.
      She was 16 years old and had abdominal distension, vomiting, abdominal cramping
      and failure to pass gas or stool. Immediately we suspected mechanical blockade of
      the intestine. Diagnosis was clinically confirmed by X-rays of the abdomen and
      with ultrasound. RESULTS: The operative treatment was indicated and we found the
      proximal bowel distended and the distal segment collapsed. The part of bowel
      necrosis was removed and anastomosis was done. CONCLUSION: When patients are
      determined to attempt suicide or have Pica disorder it is very difficult to
      prevent.

PMID- 21842727
TI  - [Comparative characteristics of lead and cadmium intoxication in the Khanty-Mansi
      autonomous district].
AB  - The Khanty-Mansi Autonomous District (KMAD) occupies a prominent place in the
      economy of Russia in oil and gas production and energy generation. The
      development of hydrocarbon raw material extraction in the district does great
      damage to the environment and nature. This results in the accumulation of toxic
      chemical elements in man. The levels of lead, cadmium, calcium, and zinc were
      measured in the hair of indigenous and non-indigenous populations of the
      district. High lead and cadmium and low calcium and zinc concentration were found
      in indigenous adults and children in the KMAD.

PMID- 21842728
TI  - [Role of the environment in the occurrence of noninfectious diseases of the
      digestive tract in the Primorie Territory].
AB  - The paper presents the results of a hygienic study to identify the leading
      regional risk factors for noninfectious diseases of the digestive tract (DT) in
      the Primorye Territory. Data on 55 environmental factors and registered deaths by
      5 groups of noninfectious DT diseases over 15 years were collected for the study.
      The authors used an original scheme for identifying risk factors for DT diseases,
      by concurrently applying a correlation and regression analysis. The chemical
      composition of portable water from the water supply system, soil contamination by
      trace elements, and socioeconomic factors showed 5.6-23.2% responsibility for the
      geographical distribution of the bulk of DT diseases. At the same time, many
      years' rises in morbidity rates among children and adolescents by 5.6-18.2% and
      adults by as high as 50% are attributable to altered daily diets and
      socioeconomic factors and to reduced access to medical care. The nature of the
      found risk factors allows one to direct the main ways to prevent non-infectious
      DT diseases among the region's population.

PMID- 21842729
TI  - [Role of Aeromonas in the monitoring of a hydroecosystem in the Volga-Caspian
      area].
AB  - The paper gives data obtained over many years on the quantity of bacteria of the
      genus Aeromonas in the hydroecosystems of the delta of the Volga and Caspian Sea
      and in commercial fishes (sturgeon (Acipenseridae), pike perch (Stizostedion),
      carp (Cyprinus carpio), silurus (Silurus glanis), etc.). It provides a detailed
      analysis of their seasonal trends and spatial distribution, markers of their
      pathogenicity, and antibiotic resistance. The findings suggest that Aeromonas is
      a causative agent of sapronoses and meets the criteria for natural focal
      infections. They show a wide range of tolerance to the abiotic factors of
      hydroecosystems, as well as mixotrophy and autrophic nutrition in the environment
      and they are of great sanitary and hygienic importance.

PMID- 21842730
TI  - [Assessment of the health status of a population living in the catchment area of
      the Kuibyshev water reservoir].
AB  - An analysis of trends in primary morbidity in the regions belonging to the
      catchment area of the Kuibyshev water reservoir within the Republic of Tatarstan
      has shown its rise in the examined classes of diseases. There is the highest
      increase in morbidity in the areas located in the river basins of Kama, Sviyaga,
      Kazanka, Mesha, which are the main tributaries of the Kuibyshev water reservoir
      in the Republic of Tatarstan. The cumulative hazard index in the assessment of a
      noncancer risk to the health of the population consuming the portable water and
      fish from the Kuibyshev reservoir is 0.34, which suggests that there is no
      serious hazard to human health. With oral intake of lead and cadmium, the cancer
      risk corresponds to the maximum acceptable value.

PMID- 21842731
TI  - [Conceptual model for assessment and management of human risk from transport
      pollution].
AB  - The existing methodology for human health risk assessment allows one to
      appreciably study cause-and-effect relationships between environmental factors
      and human health. Risk management is a logic continuation of the assessment of
      human health risk and it is aimed at substantiating the choice of decisions that
      are best in a specific situation to eliminate or minimize it, to make follow-up
      monitoring of exposures and a risk, to evaluate the efficiency of health
      improving measures and to correct the latter. Risk management involves technical,
      technological, organizational, social, legal, economic, normative, political, and
      other decisions made on the conclusions and estimates obtained when
      characterizing the risk.

PMID- 21842732
TI  - [Cancer risk assessment in a group of traffic officers].
AB  - Air-pollution studies in the area where the traffic officers of the road-patrol
      service of the State Inspectorate for Road Traffic Safety, who patrol road
      traffic safety, breathe at the stationary militia inspection stations (MIS) and
      in the areas of the heaviest motor traffic highways of a city ascertained the
      cancer risk from exposure to carcinogenic agents, such as benzo(a)pyrene,
      benzene, and formaldehyde. The mean concentrations of these substances do not
      exceed the hygienic limits. In terms of the hazard index (1.04) and the
      individual's cancer risk index (4.8 x 10(-5)), the cancer risk for the traffic
      officers of MIS may be considered acceptable. Both indices (1.28 and 1.3 x 10(
      4), respectively) for traffic officers and traffic controllers are suggestive of
      an increased cancer risk, which constitutes a potential threat to a rise in
      cancer morbidity in this occupational group and needs preventive measures to be
      undertaken.

PMID- 21842733
TI  - [The content of hazardous substances in the air of the central laboratory of the
      Astrakhan gas processing plant].
AB  - The degree and nature of air pollution were studied at the central laboratory of
      the Astrakhan gas processing plant. Priority pollutants were established and
      their sources indicated.

PMID- 21842734
TI  - [Hygienic features of working conditions and their impact on the health of women
      engaged in the present-day manufacture of paper wallpaper].
AB  - The purpose of the investigation was to comprehensively assess working conditions
      and their impact on the health of female workers engaged in the manufacture of
      present-day paper wallpaper. A complex of sanitary-and-hygienic, clinical-and
      physiological, sociomedical, and statistical studies was used to tackle the tasks
      set in the investigation. Stage 1 made a sanitary-and-hygienic assessment of
      industrial factors (microclimate, noise, vibration, the content of toxicants and
      dust) in the workplaces of female workers from the papering shops using an Elita
      rolling automatic machine. The following stage analyzed morbidity among the
      workers and identified a number of functional parameters. A combination of poor
      factors characterizing their parameters and exceeding the sanitary standards
      influenced on the workers engaged in the manufacture of paper wallpaper. The
      leading harmful industrial factors are heating microclimate, production noise,
      and the working air level of harmful chemical substances in the working air. The
      production process under such microclimatic conditions causes the body's thermal
      changes characterized by the senses of total warm discomfort and the tension of
      thermoregulatory mechanisms, as confirmed by weighed mean skin temperature
      studies and decreased working capacity. The working conditions in the manufacture
      of wallpaper products are shown to result in an increase in female morbidity.

PMID- 21842735
TI  - [Complex hygienic evaluation of working conditions and environmental protection
      at glass works].
AB  - The working conditions and sanitary-and-hygienic state of the Kvarts glass works
      in the town of Kuvasai were studied. Harmful industrial factors were shown to
      influence on the incidence of disease with temporary disability; atmospheric
      emission of pollutants and discharge of sewage were calculated. The results of
      the analysis were assessed in the hygienic point and necessary recommendations to
      improve working conditions and the environment.

PMID- 21842736
TI  - [Hygienic evaluation of the specific features of eating behavior and
      anthropometric parameters in Kuzbass miners].
AB  - Investigations were conducted in coal mines. The eating behavior and
      anthropometric characteristics of miners became an object of the investigation.
      Questionnaire interviews were carried out to study their eating behavior. Body
      mass index and body composition were determined using the Watson formulas for the
      assessment of anthropometric measurements. The specific features of the miners'
      eating behavior were established. Eating behavioral disorders were ranked by
      prevalence. Eating behavior was shown to be involved in the formation of
      anthropometric characteristics in the miners.

PMID- 21842737
TI  - [The hygienic features of nutrition and elemental status in the children of the
      Orenburg region].
AB  - The paper analyzes the trace element status in the children residing in Orenburg
      and the Sakmarsky District, Orenburg Region. The study was conducted among 2nd
      3rd-form pupils. Their hair samples were used as a biosubstrate to ascertain the
      trace element status; chemical elements were determined in accordance with
      guidelines 4.1.1482-03 and 4.1.1483-03 approved by the Ministry of Health of the
      Russian Federation in 2003. The studies ascertained the children's trace element
      profiles that are indicative of the high prevalence of imbalance in the hair
      content of elements among the rural children in the presence of inadequate
      nutrition in both rural and urban schoolchildren.

PMID- 21842738
TI  - [Hygienic bases for management of bottled drinking water quality].
AB  - The paper analyzes the existing normative requirements, by controlling the
      packaged drinking waters versus tap water; substantiates additions into a list,
      the regulated levels of a number of indices for this type of products, including
      those for the waters designed for babies, and the narrowed list of indices for
      state control. To assure the high quality of finished products, it is shown to be
      important to perform a sanitary-and-epidemiological study of raw water for
      pouring and finished products in full conformity with normative documents and to
      use current water conditioning technologies by the level of major biogenic
      elements to have physiologically adequate waters of high quality.

PMID- 21842739
TI  - [Characteristics of the biochemical status of urban versus rural general
      educational school pupils].
AB  - The paper gives the results of a study of the biochemical status of general
      educational school pupils in Orenburg and the Sakmarsky District, Orenburg
      Region. The findings suggest that biochemical abnormalities found in the urban
      and rural schoolchildren may result from nutrition that is irrational and
      inadequate in terms of their age and gender.

PMID- 21842740
TI  - [Schoolchildren's attitude towards health in the aspect of tobacco smoking: a
      sociohygienic study].
AB  - The paper presents the results of a sociological survey of 1093 Moscow 6th-11th
      form schoolchildren. Their awareness and real behavior are analyzed in the
      context of smoking and health. The adolescents have been found to have
      superficial knowledge of the negative effect of smoking on health. Among the
      schoolchildren, the prevalence of varying intensity smoking is 45.6%.
      Susceptibility to smoking increases by 3 and 5 times in the middle and senior
      classes, respectively. The number of smoking adolescents peaks (41.1%) in the
      10th-11th classes. This group of adolescents shows no gender differences: the
      smoking boys and girls are 42.1 and 40.0%, respectively. Despite the fact that
      the adolescents have a firm grasp of health protection, the reality shows a
      substantial difference between the acceptable values and real behavior.

PMID- 21842741
TI  - [Hygienic aspects of the lifestyle of medical students under the present
      conditions].
AB  - The paper gives the results of a study of the lifestyle of medical students. The
      students' motor activity has been found to be lower and to continue to drop in
      the undergraduates. Examination of the daily routine has shown that 92% of the
      students break the study-and-rest routine; the reported reasons for this are a
      high academic load, a prolonged academic day, a study-work combination, mental
      stress during examinations, and computer-aided learning. The students' nutrition
      is inadequate in major nutrients, poor-quality, irregular, and uncontrolled. The
      college crowd shows a preponderance of bad habits; 85% of cases had these or
      those combinations of risk factors: smoking, low motor activity, overweight,
      alcohol consumption, etc.

PMID- 21842742
TI  - [Changes in the red blood cell system and in the activity of free radical
      processes in rats during chronic nitrite intoxication and alpha-tocopherol
      administration].
AB  - The red blood cell system and the activity of free radical processes were studied
      in pregnant rats during chronic nitrite intoxication (oral 0.2% sodium nitrite
      solution) and during alpha-tocopherol administration (in an intramuscular dose of
      150 mg/kg). In intact pregnant rats, alpha-tocopherol decreased the activity of
      free radical processes and increased the antioxidant potential. Its
      administration to pregnant rats with nitrite intoxication prevents the elevated
      concentration of hemoglobin, considerably decreases the activity of free radical
      processes, and increases the antioxidant activity of serum.

PMID- 21842743
TI  - [Sociohygienic monitoring of the working conditions of workers at an aircraft
      engine factory].
AB  - The authors have improved, modified, and introduced a sociohygienic monitoring
      model proposed by Yu. V. Erofeyev, V. V. Dalmatov, and D. V. Turchaninov (2007)
      in the P. I. Baranov engine association and proposed objective criteria for
      evaluating the work space.

PMID- 21842744
TI  - [Study of the mechanisms of interaction between intestinal bacteriophages and
      polyaluminum coagulants].
AB  - The authors have investigated the adsorption-elution of intestinal bacteriophages
      T2 and MS2 as a model of enteric viruses, by using the coagulants aluminum
      oxychloride (AOX78) and aluminum sulfate (AS). The investigation has ascertained
      the effective removal of the phages from water with AOX78 (98.7-100%) and the low
      efficiency of elution of coliphages from the particles of AOX hydrolysis products
      (0.1-3.7% of the baseline count of bacteriophages), which may suggest that AOX
      has antiviral activity. The above phenomena produced by AS are less evident.

PMID- 21842745
TI  - [Economic evaluation and rationale for human health risk management decisions].
AB  - The priority task of human health maintenance and improvement is risk management
      using the new economic concepts based on the assessment of potential and real
      human risks from exposure to poor environmental factors and on the estimation of
      cost-benefit and cost-effectiveness ratios. The application of economic tools to
      manage a human risk makes it possible to assess various measures both as a whole
      and their individual priority areas, to rank different scenarios in terms of
      their effectiveness, to estimate costs per unit of risk reduction and benefit
      increase (damage decrease).

PMID- 21842746
TI  - [Regional standardization of water chemical substances in case of the Arkhangelsk
      region].
AB  - The paper gives the data characterizing the status of water supply systems, the
      efficiency of waterworks, and the quality of drinking and Severnaya Dvina River
      waters. It generalizes the data characterizing the sanitary-and-epidemiological
      situation and human health in the region. There is evidence for the assumption
      that regional standardization of chemical compounds in the drinking water of
      northern regions should be carried out during water preparation, which confirms
      the conclusions of hygienic and toxic studies previously conducted in individual
      areas and those given in the references.

PMID- 21842747
TI  - [Bioavailability and metabolism of flavonoids].
AB  - In the review the modern data about bioavailability and a metabolism of
      flavonoids is considered. The data about absorption flavonoids in a digestive
      path, participation of microorganisms in their hydrolysis, pharmacokinetic the
      data on the basic classes flavonoids: flavanes (flavan-3-ols), anthocyanes,
      flavones, flavonols and flavanones is cited.

PMID- 21842748
TI  - [The study of polymorphism rs9939609 FTO gene in patients with overweight and
      obesity].
AB  - In 94 persons living in the Moscow region, with a body mass index >25 kg/m2 were
      identified on the polymorphism rs9939609 FTO gene. The results showed that 83% of
      them were carriers of the mutant allele, and 43%--contained the mutant allele in
      the homozygous state. Carriers of the mutant allele rs9939609 FTO gene were
      distinguished by higher absolute and relative values of fat mass and
      triglycerides in serum.

PMID- 21842749
TI  - [Modern presentation of role of nutrition and genetic factors in the development
      of metabolic syndrome].
AB  - The role of dietary and hereditary factors in the development of metabolic
      syndrome is discussed in this review.

PMID- 21842750
TI  - [Bioavailability of nanoparticles of ferric oxide when used in nutrition.
      Experimental results in rats].
AB  - Bioavailability of iron (Fe) introduced in the form of nanoparticles of ferric
      oxide and ferric sulphate was characterized in rats receiving Fe-deficient semi
      synthetic diet. Shown that nanoparticles of ferric oxide as well as the
      traditional form of this trace element (soluble salt of Fe) can restore the
      status of this trace element disturbances due to its scarcity in the diet.

PMID- 21842751
TI  - [The influence assessment of probiotic fermented milk products on intestinal
      microflora, hematological indices and cellular immunity in rats (report 1)].
AB  - Influence of probiotic fermented milk products on the intestinal flora,
      hematological parameters and immune status of the experiment in vivo at rats is
      studied. Entering in digestive tract of probiotic strains of Lactobacillus
      acidophilus NK-1 and Bifidobacterium bifidum 791 at the level of hundreds of
      millions CFU in a day (from 1,7 x 10(8) to 9 x 10(8) CFU) in composition
      fermented milk products renders on the whole positive, but not significant
      statistically influence on the indexes of colon microflora and immune status of
      rats, and it must be extended for the achievement of reliable effect.

PMID- 21842752
TI  - [Influence of lactobacillus strains used in the production of dairy products on
      the agents of food poisoning].
AB  - Study of antagonistic activity of 33 strains of Lactobacillus isolated from the
      industrial preparation of fermented milk products, starter cultures and
      biologically active additives and products of natural fermentation. Antagonistic
      activity was studied by agar diffusion method with holes. Strains isolated from
      products of natural fermentation showed high degree of antagonistic action
      together with industrial strains.

PMID- 21842753
TI  - [Nutritional value of sesame seeds].
AB  - Literature data on the nutritional value of sesame seeds (Sesamum indicum L.),
      their use in feeding the world population and food production are presented.
      Sesame seeds contain up to 55% oil and 20% protein. Sesame proteins are limited
      by lysine but rich in tryptophan and methionine. Sesame oil is rich in linoleic
      and oleic acids, the predominance of gamma-tocopherol over the other isomers of
      vitamin E and high content of fat-soluble lignans (sesamin and sesamolin). Thanks
      to recent sesame oil has a phytoestrogen activity; it has a cholesterol-lowering
      effect.

PMID- 21842754
TI  - [Effectiveness of cultured milk foods, enriched by bifidus bacteria and
      Lactobacillus rhamnosis GG (ATCC 53103, LGG) in patients with slackening of
      motility function of intestines].
AB  - In patients who consumed yogurt and kefir, enriched by bifidus bacteria and
      Lactobacillus rhamnosis GG, improvement of large intestine motor function was
      found.

PMID- 21842755
TI  - [Actual vitamin and main foodstuffs consumption by recovered patients suffered
      from hemorrhagic fever with renal syndrome].
AB  - Actual consumption of vitamins A, E, beta-carotene, ascorbic acid, thiamin,
      pyridoxine and main foodstuffs by recovered patients suffered from hemorrhagic
      fever with renal syndrome has been given. Frequency analysis of foodstuffs
      consumption was used to study actual nourishment of recovered patients. Surplus
      consumption of fat mainly due to the use of saturated fatty acids, deficiency of
      poly unsaturated fatty acids, surplus sugar consumption and predominance of
      proteins of animal origin over proteins of vegetable origin in ration has been
      revealed. Deficiency of water soluble vitamins equals to 41,6-78,7% of all
      examined patients, deficiency of fat water soluble vitamins is lower (21,4
      38,3%).

PMID- 21842756
TI  - [Insulin resistance and carbohydrate metabolism indexes in women of reproductive
      age depending on the type of their breast-feeding in infancy].
AB  - Determine what in women in early age exceptionally on artificial nutrition risk
      beginning insulin resistance and breach carbohydrate metabolism more high than in
      women receive in pectoral age naturally nutrition. This relation especially
      distinctly reveals in women with obesity.

PMID- 21842757
TI  - [Clinical effects of application of taurines in patients with metabolic
      syndrome].
AB  - Study on the influence of taurines (Dibicor) on metabolic indicators in patients
      with of metabolic syndrome showed improvement in carbohydrate metabolism and
      lipid profile in patients with type 2 pancreatic diabetes.

PMID- 21842758
TI  - [Contemporary methods of daily energy expenditure measurement in the system of
      the nutritional status estimation].
AB  - Daily energy expenditure measurement have great significance in such fields of
      research as nutrition, medicine, sport, physical activity, way of life, etc.
      Article is dedicated to the survey of the principal methods of the energy
      expenditure measurement: direct calorimetry, the double labeled water method,
      indirect calorimetry, heart rate monitoring, and accelerometry. For evaluating
      the daily energy expenditure most informative is the combination of indirect
      calorimetry, heart rate monitoring and accelerometry.

PMID- 21842759
TI  - [Methods quantitative for determination of water-soluble vitamins in premixes and
      fortified food products by micellar electrokinetic chromatography on short end of
      the capillary].
AB  - It was purposed new technique by micellar electrokinetic chromatography on short
      end of the capillary (capillary electrophoresis system Agilent 3D CE, DAD, quartz
      capillary HPCE stndrd cap 56 cm, 50 microm, 50 mM borate buffer pH=9,3, 100 mM
      sodium dodecil sulfate) for simultaneous determination of water-soluble vitamins
      (B1, B2, B6, B12, PP, B5, B9, C, B8) in fortified food products and premixes. It
      was observed on 6 samples of vitamin premixes and 28 samples of fortified food
      products using this technique. Our findings are consistent with the results of
      research on certain vitamins, conducted by other methods. The developed technique
      can be used in analysis of water-soluble vitamins in premixes and fortified food
      products.

PMID- 21842760
TI  - [The activity of antioxidant enzymes of erythrocytes under intensive physical
      activity on the background of D-ribose use].
AB  - Biochemical analysis of blood of 30 male rats with 240 +/- 20 g mass and 50
      sportsmen at the age 17-20 years were done. They were subjected by intensive
      physical activity with D-ribose use and without it. Carbohydrate was being put
      into them before and after intensive physical activity during 5-7 days. The dose
      was 30-50 mg/kg of their body mass. Concentration of glucose, lactate and uric
      acids, level of malondialdehyde, activity of superoxide dismutase, glutathione
      peroxidase and glucose-6-phosphate dehydrogenase were defined in the male rats
      and sportsmen blood. It is shown that D-ribose use influences positive by to the
      dynamics of biochemical data in blood. It has taken place owing to the
      intensification of reutilization of purine mononucleotides and the activity of
      pentose cycle, as a result lipid peroxidation of membrane of erythrocytes reduces
      and state of antioxidation system improves.

PMID- 21842768
TI  - Ultrasensitive culture in urinary tract infection diagnosis.

PMID- 21842770
TI  - The physician's role in efforts to slow global warming.

PMID- 21842771
TI  - The race against time: coping with anxiety and depression.

PMID- 21842772
TI  - Self-monitoring and self-management of anticoagulation therapy.

PMID- 21842774
TI  - Global warming and your health.

PMID- 21842773
TI  - Slowing global warming: benefits for patients and the planet.
AB  - Global warming will cause significant harm to the health of persons and their
      communities by compromising food and water supplies; increasing risks of
      morbidity and mortality from infectious diseases and heat stress; changing social
      determinants of health resulting from extreme weather events, rising sea levels,
      and expanding flood plains; and worsening air quality, resulting in additional
      morbidity and mortality from respiratory and cardiovascular diseases. Vulnerable
      populations such as children, older persons, persons living at or below the
      poverty level, and minorities will be affected earliest and greatest, but
      everyone likely will be affected at some point. Family physicians can help reduce
      greenhouse gas emissions, stabilize the climate, and reduce the risks of climate
      change while also directly improving the health of their patients. Health
      interventions that have a beneficial effect on climate change include encouraging
      patients to reduce the amount of red meat in their diets and to replace some
      vehicular transportation with walking or bicycling. Patients are more likely to
      make such lifestyle changes if their physician asks them to and leads by example.
      Medical offices and hospitals can become more energy efficient by recycling,
      purchasing wind-generated electricity, and turning off appliances, computers, and
      lights when not in use. Moreover, physicians can play an important role in
      improving air quality and reducing greenhouse gas emissions by advocating for
      enforcement of existing air quality regulations and working with local and
      national policy makers to further improve air quality standards, thereby
      improving the health of their patients and slowing global climate change.

PMID- 21842776
TI  - Treating warts.

PMID- 21842775
TI  - Treatment of nongenital cutaneous warts.
AB  - Numerous treatments for nongenital cutaneous warts are available, although no
      single therapy has been established as completely curative. Watchful waiting is
      an option for new warts because many resolve spontaneously. However, patients
      often request treatment because of social stigma or discomfort. Ideally,
      treatment should be simple and inexpensive with low risk of adverse effects.
      Salicylic acid has the best evidence to support its effectiveness, but it is slow
      to work and requires frequent application for up to 12 weeks. Cryotherapy with
      liquid nitrogen is a favorable option for many patients, with cure rates of 50 to
      70 percent after three or four treatments. For recalcitrant warts, Candida or
      mumps skin antigen can be injected into the wart every three to four weeks for up
      to three treatments. More expensive treatments for recalcitrant warts are offered
      in many dermatology offices. Photodynamic therapy with aminolevulinic acid has
      the best evidence of effectiveness compared with pulsed dye laser, intralesional
      bleomycin, and surgical removal using curettage or cautery.

PMID- 21842778
TI  - Nonhealing vulvar ulcer.

PMID- 21842777
TI  - Diagnostic approach to chronic constipation in adults.
AB  - Constipation is traditionally defined as three or fewer bowel movements per week.
      Risk factors for constipation include female sex, older age, inactivity, low
      caloric intake, low-fiber diet, low income, low educational level, and taking a
      large number of medications. Chronic constipation is classified as functional
      (primary) or secondary. Functional constipation can be divided into normal
      transit, slow transit, or outlet constipation. Possible causes of secondary
      chronic constipation include medication use, as well as medical conditions, such
      as hypothyroidism or irritable bowel syndrome. Frail older patients may present
      with nonspecific symptoms of constipation, such as delirium, anorexia, and
      functional decline. The evaluation of constipation includes a history and
      physical examination to rule out alarm signs and symptoms. These include evidence
      of bleeding, unintended weight loss, iron deficiency anemia, acute onset
      constipation in older patients, and rectal prolapse. Patients with one or more
      alarm signs or symptoms require prompt evaluation. Referral to a subspecialist
      for additional evaluation and diagnostic testing may be warranted.

PMID- 21842779
TI  - Updated dietary guidelines from the USDA and HHS.

PMID- 21842780
TI  - Do vaginal estrogens increase endometrial proliferation risk?

PMID- 21842781
TI  - Case report: agranulocytosis attributed to levamisole-tainted cocaine.

PMID- 21842783
TI  - Should all children be screened for autism spectrum disorders? Yes: merging
      science, policy, and practice.

PMID- 21842784
TI  - Should all children be screened for autism spectrum disorders? No: screening is
      not ready for prime time.

PMID- 21842785
TI  - FPIN's clinical inquiries. Preventing acute mountain sickness.

PMID- 21842787
TI  - Using canes and walkers.

PMID- 21842786
TI  - Geriatric assistive devices.
AB  - Disability and mobility problems increase with age. Assistive devices such as
      canes, crutches, and walkers can be used to increase a patient's base of support,
      improve balance, and increase activity and independence, but they are not without
      significant musculoskeletal and metabolic demands. Most patients with assistive
      devices have never been instructed on the proper use and often have devices that
      are inappropriate, damaged, or are of the incorrect height. Selection of a
      suitable device depends on the patient's strength, endurance, balance, cognitive
      function, and environmental demands. Canes can help redistribute weight from a
      lower extremity that is weak or painful, improve stability by increasing the base
      of support, and provide tactile information about the ground to improve balance.
      Crutches are useful for patients who need to use their arms for weight bearing
      and propulsion and not just for balance. Walkers improve stability in those with
      lower extremity weakness or poor balance and facilitate improved mobility by
      increasing the patient's base of support and supporting the patient's weight.
      Walkers require greater attentional demands than canes and make using stairs
      difficult. The top of a cane or walker should be the same height as the wrist
      crease when the patient is standing upright with arms relaxed at his or her
      sides. A cane should be held contralateral to a weak or painful lower extremity
      and advanced simultaneously with the contralateral leg. Clinicians should
      routinely evaluate their patients' assistive devices to ensure proper height,
      fit, and maintenance, and also counsel patients on correct use of the device.

PMID- 21842789
TI  - Prostate cancer: who should be treated?

PMID- 21842788
TI  - Treatment options for localized prostate cancer.
AB  - In the United States, more than 90 percent of prostate cancers are detected by
      serum prostate-specific antigen testing. Most patients are found to have
      localized prostate cancer, and most of these patients undergo surgery or
      radiotherapy. However, many patients have low-risk cancer and can follow an
      active surveillance protocol instead of undergoing invasive treatments. Active
      surveillance is a new concept in which low-risk patients are closely followed and
      proceed to intervention only if their cancer progresses. Clinical guidelines can
      help in selecting between treatment or active surveillance based on the cancer's
      stage and grade, the patient's prostate-specific antigen level, and the
      comorbidity-adjusted life expectancy. Radical prostatectomy or external beam
      radiation therapy is recommended for higher-risk patients. These treatments are
      almost equivalent in effectiveness, but have different adverse effect profiles.
      Brachytherapy is an option for low- and moderate-risk patients. Evidence is
      insufficient to determine whether laparoscopic or robotic surgery or cryotherapy
      is superior to open radical prostatectomy.

PMID- 21842790
TI  - Exercise-induced bronchoconstriction: diagnosis and management.
AB  - Exercise-induced bronchoconstriction describes the narrowing of the airway that
      occurs with exercise. More than 10 percent of the general population and up to 90
      percent of persons previously diagnosed with asthma have exercise-induced
      bronchoconstriction. Common symptoms include coughing, wheezing, and chest
      tightness with exercise; however, many athletes will present with nonspecific
      symptoms, such as fatigue and impaired performance. Spirometry should be
      performed initially to evaluate for underlying chronic asthma, although results
      are often normal. An empiric trial of short-acting beta2 agonists or additional
      bronchial provocation testing may be necessary to confirm the diagnosis.
      Nonpharmacologic treatment options include avoiding known triggers, choosing
      sports with low minute ventilation, warming up before exercising, and wearing a
      heat exchange mask in cold weather. Short-acting beta2 agonists are recommended
      first-line agents for pharmacologic treatment, although leukotriene receptor
      antagonists or inhaled corticosteroids with or without long-acting beta2 agonists
      may be needed in refractory cases. If symptoms persist despite treatment,
      alternative diagnoses such as cardiac or other pulmonary etiologies, vocal cord
      dysfunction, or anxiety should be considered.

PMID- 21842791
TI  - Exercise-induced wheezing.

PMID- 21842793
TI  - Photo quiz. A bubble under the tongue of a child.

PMID- 21842795
TI  - Screening for testicular cancer.

PMID- 21842798
TI  - Special issue: Chronic illness care.

PMID- 21842799
TI  - Why I let my patients see my notes.

PMID- 21842802
TI  - Medicare's new home health services requirement.

PMID- 21842803
TI  - Registries made simple.

PMID- 21842805
TI  - Encouraging patients to change unhealthy behaviors with motivational
      interviewing.

PMID- 21842804
TI  - Keys to high-functioning office teams.

PMID- 21842806
TI  - An organized approach to chronic disease care.

PMID- 21842817
TI  - Letting your patients see your notes.

PMID- 21842816
TI  - The perils of employment.

PMID- 21842819
TI  - Challenging the health IT hype.

PMID- 21842820
TI  - Medicare annual wellness visits made easier.

PMID- 21842821
TI  - Structure and synchronicity for better charting.

PMID- 21842822
TI  - Why did your productivity decrease when we hired you?

PMID- 21842823
TI  - The 2011 EHR User Satisfaction Survey: responses from 2,719 family physicians.

PMID- 21842830
TI  - Five signs you may have joined the wrong practice.

PMID- 21842831
TI  - Blood plasma sample preparation method for the assessment of thyroid hormone
      disrupting potency in effect-directed analysis.
AB  - A sample preparation method combining solid-phase extraction (SPE) and liquid
      liquid extraction (LLE) was developed to be used in Effect-Directed Analysis
      (EDA) of blood plasma. Until now such a method was not available. It can be used
      for extraction of a broad range of thyroid hormone (TH)-disruptors from plasma
      with high recoveries. Validation of the method using spiked cow plasma showed
      good recoveries for hydroxylated polybrominated diphenyl ethers (OH-PBDEs; 93.8
      +/- 19.5%), hydroxylated polychlorinated biphenyls (OH-PCBs; 93.8 +/- 15.5%),
      other halogenated phenols (OHPs; 107 +/- 8.1%), and for short-chain (<8 C-atoms)
      perfluoroalkyl substances (PFASs; 85.2 +/- 24.6%). In the same extracts, the
      potency of the compound classes spiked to the cow plasma to competitively bind to
      transthyretin (TTR) was recovered by 84.9 +/- 8.8%. Furthermore, the SPE-LLE
      method efficiently removed endogenous THs from the extracts, thereby eliminating
      their possible contribution to the binding assay response. The SPE-LLE method was
      applied to polar bear plasma samples to investigate its applicability in future
      EDA studies focusing on TH-disrupting compounds in this top predator species that
      is exposed to relatively high levels of bioaccumulating pollutants. A first
      screening revealed TTR-binding potency in the polar bear plasma extracts, which
      could be explained for 60-85% by the presence of OH-PCBs.

PMID- 21842832
TI  - Tocopherol and ascorbate have contrasting effects on the viability of
      microencapsulated Lactobacillus rhamnosus GG.
AB  - The antioxidants, sodium ascorbate and tocopherol, have contrasting effects on
      the viability of microencapsulated Lactobacillus rhamnosus GG (LGG) spray-dried
      powders during storage (4 and 25  degrees C; 32, 57, and 70% relative humidity).
      The addition of tocopherol improved probiotic viability during storage, while the
      incorporation of Na-ascorbate alone or in combination with tocopherol had
      detrimental effects on probiotic survival. The beneficial effect of tocopherol is
      a consequence of its chemical antioxidative action. The reduced viability in Na
      ascorbate containing microcapsule formulations is hypothesized to be due
      primarily to the production of acetic acids arising from chemical degradation
      reactions and the catabolism of ascorbate by LGG. This study highlights the
      importance of considering the detrimental consequences of degradative chemical
      reactions and the metabolic fate of additives on the viability of probiotics when
      designing probiotic encapsulant formulations.

PMID- 21842833
TI  - Oxidative stress, genotoxicity, and vascular cell adhesion molecule expression in
      cells exposed to particulate matter from combustion of conventional diesel and
      methyl ester biodiesel blends.
AB  - Our aim was to compare hazards of particles from combustion of biodiesel blends
      and conventional diesel (D(100)) in old and improved engines. We determined DNA
      damage in A549 cells, mRNA levels of CCL2 and IL8 in THP-1 cells, and expression
      of ICAM-1 and VCAM-1 in human umbilical cord endothelial cells (HUVECs).
      Viability and production of reactive oxygen species (ROS) were investigated in
      all cell types. We collected particles from combustion of D(100) and 20% (w/w)
      blends of animal fat or rapeseed oil methyl esters in light-duty vehicle engines
      complying with Euro2 or Euro4 standards. Particles emitted from the Euro4 engine
      were smaller in size and more potent than particles emitted from the Euro2 engine
      with respect to ROS production and DNA damage, but similarly potent concerning
      cytokine mRNA expression. Particles emitted from combustion of biodiesel blends
      were larger in size, and less or equally potent than particles emitted from
      combustion of D(100) concerning ROS production, DNA damage and mRNA of CCL2 and
      IL8. ICAM-1 and VCAM-1 expression in HUVECs was only increased by D(100)
      particles from the Euro4 engine. This suggests that particle emissions from
      biodiesel in equal mass concentration are less toxic than conventional diesel.

PMID- 21842834
TI  - Hydrolysis of glycosides with microgel catalysts.
AB  - A dormant macromolecular catalyst was prepared by polymerization of an aqueous
      styrene-butyl acrylate miniemulsion in the presence of a new polymerizable
      pentadentate ligand. The catalyst was activated by binding Cu(II) ions to the
      ligand site and then explored for its ability to hydrolyze glycosidic bonds in
      alkaline solution. The performance was correlated to the catalytic activity shown
      by low molecular weight analogs. A turnover rate of up to 43 * 10(-4) min(-1) was
      previously observed for cleavage of the glycosidic bond in selected p
      nitrophenylglycosides with a binuclear, low molecular weight catalyst; by
      contrast, the same reaction is more than 1 order of magnitude faster and has a
      turnover rate of up to 380 * 10(-4) min(-1) when using the prepared
      macromolecular catalyst. The catalyzed hydrolysis is about 10(5)-fold accelerated
      over the uncatalyzed background reaction under the provided conditions, while a
      significant discrimination of the alpha- and beta-glycosidic bond or of the
      galacto- and gluco-configuration in the sugar moiety in the glycoside substrates
      is not observed.

PMID- 21842836
TI  - Nickel-catalyzed tetramerization of alkynes: synthesis and structure of
      octatetraenes.
AB  - In the presence of a catalytic system comprised of NiBr(2)(dppe) and Zn,
      arylacetylenes undergo tetramerization to form linear octatetraenes, generally in
      good to excellent yields. The structure of the coupling products was verified by
      X-ray crystallography.

PMID- 21842835
TI  - Stereoselective synthesis of F-ring saturated estrone-derived inhibitors of
      Hedgehog signaling based on cyclopamine.
AB  - Previous work in this laboratory established that the readily available F-ring
      aromatic analog of cyclopamine is a highly potent inhibitor of Hedgehog
      signaling. The synthesis and biological evaluation of two F-ring saturated
      analogs that are more potent than the F-ring aromatic structure are reported.

PMID- 21842837
TI  - Active DLP hyperspectral illumination: a noninvasive, in vivo, system
      characterization visualizing tissue oxygenation at near video rates.
AB  - We report use of a novel hyperspectral imaging system utilizing digital light
      processing (DLP) technology to noninvasively visualize in vivo tissue oxygenation
      during surgical procedures. The system's novelty resides in its method of
      illuminating tissue with precisely predetermined continuous complex spectra. The
      Texas Instruments digital micromirror device, DMD, chip consisting of 768 by 1024
      mirrors, each 16 MUm square, can be switched between two positions at 12.5 kHz.
      Switching the appropriate mirrors controls the intensity of light illuminating
      the tissue as a function of wavelength, active spectral illumination. Meaning,
      the tissue can be illuminated with a different spectrum of light within 80 MUs.
      Precisely, predetermined spectral illumination penetrates into patient tissue,
      its chemical composition augments the spectral properties of the light, and its
      reflected spectra are detected and digitized at each pixel detector of a silicon
      charge-coupled device, CCD. Using complex spectral illumination, digital signal
      processing and chemometric methods produce chemically relevant images at near
      video rates. Specific to this work, tissue is illuminated spectrally with light
      spanning the visible electromagnetic spectrum (380 to 780 nm). Spectrophotometric
      images are detected and processed visualizing the percentage of oxyhemoglobin at
      each pixel detector and presented continuously, in real time, at 3 images per
      second. As a proof of principle application, kidneys of four live anesthetized
      pigs were imaged before, during, and after renal vascular occlusion. DLP
      Hyperspectral Imaging with active spectral illumination detected a 64.73 +/- 1.5%
      drop in the oxygenation of hemoglobin within 30 s of renal arterial occlusion.
      Producing chemically encoded images at near video rate, time-resolved
      hyperspectral imaging facilitates monitoring renal blood flow during animal
      surgery and holds considerable promise for doing the same during human surgical
      interventions.

PMID- 21842838
TI  - Jasisoquinolines A and B, architecturally new isoquinolines, from a marine sponge
      Jaspis sp.
AB  - Two architecturally new isoquinolines, jasisoquinolines A and B, were isolated
      from a marine sponge Jaspis sp. as cathepsin B inhibitors. Their structures were
      determined by a combination of spectroscopic analyses and chemical methods. Both
      jasisoquinolines A and B inhibit cathepsin B with an IC(50) value of 10 MUg/mL.

PMID- 21842839
TI  - [3+2] coupling of quinone monoacetals by combined acid-hydrogen bond donor.
AB  - The expeditious and efficient [3+2] coupling approach of quinone monoacetals 1
      with alkene nucleophiles 2 by the action of an activated Bronsted acid in the
      presence of a hydrogen bond donor perfluorinated alcohol has been achieved. With
      the optimized combined acid, the reaction could proceed under mild conditions by
      only mixing the two reactants to afford the cycloadducts 3 in a short time
      (within 10 min) with good to quantitative yields.

PMID- 21842840
TI  - Formation of a cyclic dimer containing two mirror image monomers in the solid
      state controlled by van der Waals forces.
AB  - Two new copillar[5]arenes were prepared. They are arranged in two completely
      different motifs, a cyclic dimer containing two monomers with two different
      conformations that are mirror images of each other and linear supramolecular
      polymers in the solid state. Not only has it been shown that to form this kind of
      dimer is a unique feature associated with pillar[5]arene macrocycles but also it
      was demonstrated that weak van der Waals forces can be used to control the self
      organization of monomers during their supramolecular polymerization process.

PMID- 21842842
TI  - Au(CN)n complexes: superhalogens with pseudohalogen as building blocks.
AB  - Electron affinity (EA) is one of the most important factors that govern
      reactivity of atoms and molecules. Chlorine, with the highest electron affinity
      (3.6 eV) of all elements in the periodic table, is a classic example of reactive
      elements. Over past thirty years, much research has been done to expand the scope
      of molecules with electron affinities even larger than that of Cl. These
      molecules, called superhalogens, have the general formula MX(n+1) where M is a
      metal atom, X is a halogen atom, and n is the valency of the metal. In this paper
      we explore the potential of pseudohalogens such as CN, which mimic the chemistry
      of halogens, to serve as building blocks of new superhalogens. Using calculations
      based on density functional theory, we show that when a central Au atom is
      surrounded by CN moieties, superhalogens can be created with electron detachment
      energies as high as 8.4 eV. However, there is a stark contrast between the
      stability of these superhalogens and that of conventional AuF(n) superhalogens.
      Whereas AuF(n) complexes are stable up to n = 5 for neutrals and n = 6 for
      anions, Au(CN)(n) complexes (with CN moieties attached individually) are
      metastable beyond n = 1 for neutrals and n = 3 for anions. We investigate the
      nature and origin of these differences. In addition, we elucidate important
      distinctions between electron affinity (EA) and adiabatic detachment energy
      (ADE), two terms that are often used synonymously in literature.

PMID- 21842841
TI  - Chiral phosphoric acid-catalyzed addition of thiols to N-acyl imines: access to
      chiral N,S-acetals.
AB  - The first catalytic asymmetric method to prepare enantioenriched N,S-acetals
      using chiral BINOL phosphoric acids is reported. The reaction combines N-acyl
      imines with thiols to generate products in excellent yield and
      enantioselectivity. The addition reaction could also be achieved with an
      exceptional substrate to catalyst (S/C) molar ratio. Electron-rich and electron
      deficient aromatic N-acyl imines, as well as a broad range of aliphatic and
      aromatic thiols, showed excellent reactivity.

PMID- 21842843
TI  - First three-dimensional inorganic-organic hybrid material constructed from an
      "inverted Keggin" polyoxometalate and a copper(I)-organic complex.
AB  - A new polyoxometalate (POM) based on a flexible bidentate ligand and "inverted
      Keggin" inorganic building block, namely,
      [Cu(8)L(8)[Mo(12)O(46)(AsPh)(4)](2)].H(2)O (1), where L is 1,3-bis(1,2,4-triazol
      1-yl)propane, has been synthesized under hydrothermal condition. In 1, the
      "inverted Keggin" [Mo(12)O(46)(AsPh)(4)](4-) building blocks are linked by the
      one-dimensional (1D) zigzag [Cu(I)(trans-L)](+) chains and [Cu(I)(4)(cis
      L)(4)](4+) macrocycles to yield a three-dimensional (3D) framework. The compound
      1 represents the first 3D "inverted Keggin" polyoxometalate modified by a
      transition-metal complex. Topologically, the 3D framework can be considered as an
      8-connected net with a Schlafli symbol of 4(22).6(6). As far as we know, compound
      1 is the highest-connected uninodal network topology presently known for POM
      based materials. The compound was characterized by its IR spectrum, UV-vis
      spectrum, thermogravimetric analysis (TGA), and powder X-ray diffraction (XRD)
      patterns. Remarkably, compound 1 exhibits photocatalytic activity for dye
      degradation under visible light irradiation and shows good stability toward
      visible-light photocatalysis.

PMID- 21842844
TI  - Facile assembly of micro- and nanoarrays for sensing with natural cell membranes.
AB  - Microarray technology has facilitated many powerful high-throughput studies in
      the fields of genetics and proteomics, among others. However, preparation of
      microarrays composed of cell-derived membranes with embedded receptors has proven
      difficult. Here we describe a new method for forming microarrays composed of
      synthetic lipid vesicles and natural cell membranes. The method is based upon
      assembly of vesicles and natural membranes into recessed micro- and nanowells and
      using a polydimethylsiloxane (PDMS) block as a "squeegee." This method is used to
      assemble phospholipid vesicles into arrays with micrometer and nanoscale
      dimensions. Native myelin and neuronal lipid raft arrays are also formed in 30
      min or less. We show the natural membrane arrays can be used for sensing lipid
      protein interactions by detecting cholera toxin binding to ganglioside GM1 in
      neuronal lipid rafts. In multicomponent arrays myelin can be distinguished from
      neuronal rafts by antibody binding to cell-specific surface antigens. Finally,
      myelin arrays formed in gold nanowells are used for surface plasmon resonance
      sensing. This assembly approach is simple, broadly applicable, and opens up new
      avenues of research not easily accomplished with standard microarray technology.

PMID- 21842845
TI  - Detection of mercury(II) by quantum dot/DNA/gold nanoparticle ensemble based
      nanosensor via nanometal surface energy transfer.
AB  - An ultrasensitive fluorescent sensor based on the quantum dot/DNA/gold
      nanoparticle ensemble has been developed for detection of mercury(II). DNA
      hybridization occurs when Hg(II) ions are present in the aqueous solution
      containing the DNA-conjugated quantum dots (QDs) and Au nanoparticles. As a
      result, the QDs and the Au nanoparticles are brought into the close proximity,
      which enables the nanometal surface energy transfer (NSET) from the QDs to the Au
      nanoparticles, quenching the fluorescence emission of the QDs. This nanosensor
      exhibits a limit of detection of 0.4 and 1.2 ppb toward Hg(II) in the buffer
      solution and in the river water, respectively. The sensor also shows high
      selectivity toward the Hg(II) ions.

PMID- 21842846
TI  - Targeting the histamine H4 receptor.

PMID- 21842847
TI  - Enantioselective hydroformylation of aniline derivatives.
AB  - We have developed a ligand that reversibly binds to aniline substrates, allowing
      for the control of regioselectivity and enantioselectivity in hydroformylation.
      In this paper we address how the electronics of the aniline ring affect both the
      binding of the substrate to the ligand and the enantioselectivity in this
      reaction.

PMID- 21842848
TI  - Nonvolatile memory device using gold nanoparticles covalently bound to reduced
      graphene oxide.
AB  - Nonvolatile memory devices using gold nanoparticles (AuNPs) and reduced graphene
      oxide (rGO) sheets were fabricated in both horizontal and vertical structures.
      The horizontal memory device, in which a singly and doubly overlayered
      semiconducting rGO channel was formed by simply using a spin-casting technique to
      connect two gold electrodes, was designed for understanding the origin of
      charging effects. AuNPs were chemically bound to the rGO channel through a pi
      conjugated molecular linker. The pi-conjugated bifunctional molecular linker, 4
      mercapto-benzenediazonium tetrafluoroborate (MBDT) salt, was newly synthesized
      and used as a molecular bridge to connect the AuNPs and rGOs. By using a self
      assembly technique, the diazonium functional group of the MBDT molecular linker
      was spontaneously immobilized on the rGOs. Then, the monolayered AuNPs working as
      capacitors were covalently connected to the thiol groups of the MBDT molecules,
      which were attached to rGOs (AuNP-frGO). These covalent bonds were confirmed by
      XPS analyses. The current-voltage characteristics of both the horizontal and
      vertical AuNP-frGO memory devices showed noticeable nonlinear hysteresis, stable
      write-multiple read-erase-multiple read cycles over 1000 s, and a long retention
      time over 700 s. In addition, the vertical AuNP-frGO memory device showed a large
      current ON/OFF ratio and high stability.

PMID- 21842849
TI  - Characterization of the human gastric fluid proteome reveals distinct pH
      dependent protein profiles: implications for biomarker studies.
AB  - Gastric fluid is a source of gastric cancer biomarkers. However, very little is
      known about the normal gastric fluid proteome and its biological variations. In
      this study, we performed a comprehensive analysis of the human gastric fluid
      proteome using samples obtained from individuals with benign gastric conditions.
      Gastric fluid proteins were prefractionated using ultracentrifuge filters (3 kDa
      cutoff) and analyzed by two-dimensional gel electrophoresis (2-DE) and
      multidimensional LC-MS/MS. Our 2-DE analysis of 170 gastric fluid samples
      revealed distinct protein profiles for acidic and neutral samples, highlighting
      pH effects on protein composition. By 2D LC-MS/MS analysis of pooled samples, we
      identified 284 and 347 proteins in acidic and neutral samples respectively (FDR
      <=1%), of which 265 proteins (72.4%) overlapped. However, unlike neutral samples,
      most proteins in acidic samples were identified from peptides in the filtrate
      (i.e., <3 kDa). Consistent with this finding, immunoblot analysis of six
      potential gastric cancer biomarkers rarely detected full-length proteins in
      acidic samples. These findings have important implications for biomarker studies
      because a majority of gastric cancer patients have neutral gastric fluid compared
      to noncancer controls. Consequently, sample stratification, choice of proteomic
      approaches, and validation strategy can profoundly affect the interpretation of
      biomarker findings. These observations should help to refine gastric fluid
      biomarker studies.

PMID- 21842850
TI  - Comment on "Preparation and characterization of silver-poly(vinylidene fluoride)
      nanocomposites: formation of piezoelectric polymorph of poly(vinylidene
      fluoride)".

PMID- 21842851
TI  - Flexible graphene-based electroluminescent devices.
AB  - For the first time, large-area CVD-grown graphene films transferred onto flexible
      PET substrates were used as transparent conductive electrodes in alternating
      current electroluminescence (ACEL) devices. The flexible ACEL device based on a
      single-layer graphene electrode has a turn-on voltage of 80 V; at 480 V (16 kHz),
      the luminance and luminous efficiency are 1140 cd/m(2) and 5.0 lm/W,
      respectively. The turn-on voltage increases and the luminance decreases with
      increasing stacked layers of graphene, which means the single-layer graphene is
      the best optimal choice as the transparent conductive electrode. Furthermore, it
      demonstrates that the graphene-based ACEL device is highly flexible and can work
      very well even under a very large strain of 5.4%, suggesting great potential
      applications in flexible optoelectronics.

PMID- 21842852
TI  - Experimental study of a 4040 spiral-wound forward-osmosis membrane module.
AB  - This paper analyzes the structural features of a spiral-wound forward-osmosis (SW
      FO) membrane module via an experimental approach and presents the relationships
      between the water flux and operating conditions for design and operation of a
      large-scale FO process. The SW FO module has four ports: an inlet/outlet for the
      draw solution and an inlet/outlet for the feed solution. Accordingly, two
      strongly interacting flow streams existed on either side of the membrane with
      spatially variable properties. Unlike the operation of a membrane cell device
      loaded with a small membrane coupon, it was appropriate to operate a housing-type
      FO unit loaded with a 4040 SW FO module with a lower draw flow rate than feed
      flow rate. Because of the structural features of the SW FO module, the draw
      solution flowed inside of the membrane envelope under a considerable pressure in
      order to overcome the flow resistance. The effect of operating conditions on the
      water flux in a 4040 SW FO module was investigated. A water flux equation based
      on a temperature-correction factor (TCF) was proposed to predict the water flux
      at a given temperature. Our study is a good reference point for designing the FO
      process and FO membrane module.

PMID- 21842853
TI  - Application of colloid probe atomic force microscopy to the adhesion of thin
      films of viscous and viscoelastic silicone fluids.
AB  - The adhesive characteristics of thin films (0.2-2 MUm) of linear
      poly(dimethylsiloxane) (PDMS) liquids with a wide range of molecular weights have
      been measured using an atomic force microscope with a colloid probe (diameters 5
      and 12 MUm) for different separation velocities. The data were consistent with a
      residual film in the contact region having a thickness of ~6 nm following an
      extended dwell time before separation of the probe. It was possible to estimate
      the maximum adhesive force as a function of the capillary number, Ca, by applying
      existing theoretical models based on capillary interactions and viscous flow
      except at large values of Ca in the case of viscoelastic fluids, for which it was
      necessary to develop a nonlinear viscoelastic model. The compliance of the atomic
      force microscope colloid beam was an important factor in governing the retraction
      velocity of the probe and therefore the value of the adhesive force, but the
      inertia of the beam and viscoelastic stress overshoot effects were not
      significant in the range of separation velocities investigated.

PMID- 21842854
TI  - Raman spectroscopic study of the tautomeric composition of adenine in water.
AB  - An experimental and theoretical study of the tautomeric composition of adenine
      (Ade) in water using Raman spectroscopy is reported. Experimental resonance Raman
      spectra of adenine at excitation wavelengths of 200, 218, and 266 nm were
      compared with quantum-mechanical calculations of N(9)H- and N(7)H-adenine
      tautomers and their cations. Both theoretical and experimental studies of
      nonresonance Raman spectra (457 nm excitation) of adenine were also performed for
      comparison. A satisfactory agreement of the calculated results with the
      experimental data was obtained. The Raman spectra are interpreted, and the basic
      regularities of the Raman intensity distribution are explained. On the basis of
      the analysis performed, the tautomeric composition of adenine in water is
      revealed. It is shown that the Ade-N(9),N(1)H(+) cation is the predominant form
      and that some neutral forms of Ade-N(9)H and Ade-N(7)H tautomers exist in water
      at pH 3.

PMID- 21842855
TI  - Hot water treatment (chronic upper lethal temperature) mitigates biofouling by
      the invasive asian mussel Limnoperna fortunei in industrial installations.
AB  - Since its introduction in South America around 1990, the freshwater mussel
      Limnoperna fortunei has become a major fouling pest for most industrial plants
      that use raw river or lake water, chiefly for cooling purposes. We assessed the
      tolerance of the mussel to upper lethal temperatures as an economical and
      environmentally innocuous method of controlling its fouling in industrial
      installations. Survival of juvenile (7 +/- 2 mm in length) and adult (21 +/- 2
      mm) individuals, acclimated to 12 and 28  degrees C, was evaluated under
      laboratory conditions. At 38-43  degrees C, all mussels die after 0.7 to 17.5 h,
      regardless of acclimation temperature and size class. At 34-36  degrees C, total
      mortality takes 25.0 to 644.3 h, regardless of the size of the animals, but
      mussels acclimated at 12  degrees C die significantly faster that those
      acclimated at 28  degrees C. Comparison of these results with the range of
      conditions currently used in the industry indicates that heat treatment is a
      viable alternative for an efficient control of this Asian mussel in fouled
      systems.

PMID- 21842856
TI  - Mechanism of YF3 nanoparticle formation in reverse micelles.
AB  - This article reports an investigation of the mechanism of YF(3) nanoparticle
      formation in two variants of the reverse microemulsion precipitation method.
      These two variants involve the addition of F(-), either as a microemulsion or
      directly as an aqueous solution, to Y(3+) dispersed in nonionic reverse micelles.
      The two methods yield amorphous and single-crystal nanoparticles, respectively.
      The kinetics of reagent mixing are studied by (19)F NMR and colorimetric model
      reactions, and the particle growth is monitored by TEM. Mixing and nucleation are
      shown to occur within seconds to minutes whereas particle growth continues for 4
      to 48 h, depending on the particle type. Moreover, the growth rate remains
      constant during most of the growth period, indicating that Ostwald ripening is
      the most probable growth mechanism. The single-emulsion method also produces a
      minority amorphous population that exhibits significantly different growth
      kinetics, attributed to a coagulation mechanism. Secondary growth experiments,
      involving the addition of precursor ions to mature particles, have been conducted
      to evaluate the relative importance of nucleation and the competitive growth of
      existing particle populations. The key differences between the two methods reside
      in the nucleation step. In the case of the classical method, nucleation occurs
      upon intermicellar collisions and under conditions of comparable concentrations
      of Y(3+) and F(-). This method generates more numerous stable nuclei and smaller
      particles. In the single-microemulsion method, nucleation occurs in the presence
      of excess F(-) through the interaction of Y(3+)-containing micelles with
      microdroplets of aqueous F(-). These conditions lead to the formation of
      crystalline particles and a wider size distribution of unstable nuclei.

PMID- 21842857
TI  - Importance of domain closure for the autoactivation of ERK2.
AB  - Extracellular signal-regulated kinases 1 and 2 (ERK1 and -2, respectively) play a
      critical role in regulating cell division and have been implicated in cancer. In
      addition to activation by MAPK/ERK kinases 1 and 2 (MEK1 and -2, respectively),
      certain mutants of ERK2 can be activated by autophosphorylation. To identify the
      mechanism of autoactivation, we have performed a series of molecular dynamics
      simulations of ERK1 and -2 in various stages of activation as well as the
      constitutively active Q103A, I84A, L73P, and R65S ERK2 mutants. Our simulations
      indicate the importance of domain closure for autoactivation and activity
      regulation, with that event occurring prior to folding of the activation lip and
      of loop L16. Results indicate that the second phosphorylation event, that of
      T183, disrupts hydrogen bonding involving D334, thereby allowing the kinase to
      lock into the active conformation. On the basis of the simulations, three
      predictions were made. G83A was suggested to impede activation; K162M was
      suggested to perturb the interface between the N- and C-domains leading to
      activation, and Q64C was hypothesized to stop folding of loop L16, thereby
      perturbing the homodimerization interface. Functional analysis of the mutants
      validated the predictions concerning the G83A and Q64C mutants. The K162M mutant
      did not autoactivate as predicted, however, which may be due to the location of
      the residue on the protein surface near the ED substrate docking domain.

PMID- 21842858
TI  - Double lactonization in triarylamine-conjugated dimethyl diethynylfumarate:
      formation of intensely colored and luminescent quadrupolar molecules including a
      missing structural isomer of Pechmann dyes.
AB  - Acid-induced double lactonization in triarylamine-conjugated dimethyl
      diethynylfumarate E-1 opens up a new synthetic route to Pechmann dyes. This one
      pot reaction affords three donor-acceptor-donor quadrupolar molecules (P(55)-1,
      P(66)-1, and P(56)-1); P(56)-1 comprises a missing structural isomer of Pechmann
      dyes. They are intensely colored and brightly luminescent. An organic field
      effect transistor device fabricated with P(66)-1 functions as a p-type
      semiconductor.

PMID- 21842859
TI  - Probing roles of lipopolysaccharide, type 1 fimbria, and colanic acid in the
      attachment of Escherichia coli strains on inert surfaces.
AB  - The roles of bacterial surface polymers in reversible (phase I) and irreversible
      (phase II) attachment (i.e., lipopolysaccharides (LPS), type 1 fimbria, and
      capsular colanic acid (CA)) were investigated in situ by combining fluorescence
      microscopy and atomic force microscopy. Fluorescence microscopy was used to
      evaluate the phase I attachment by counting the total number of cells on the
      substrata, and AFM was applied to image the phase II cells and measure the
      lateral detachment force to characterize phase II attachment. Also, by comparing
      the number of cells in phases I and II, the transformation ratio was calculated
      and used as an index to evaluate the roles of different polymers in the
      attachment process. Escherichia coli K-12 and its six mutants, which had
      different surface polymers in terms of LPS structures, CA contents, and type 1
      fimbriae, were used as the test strains. Six different materials were applied as
      substrata, including glass, two metals (aluminum and stainless steel), and three
      plastics (polyvinyl chloride, polycarbonate, and polyethylene). The results
      indicated that LPS significantly enhanced phases I and II attachment as well as
      the transformation ratio from phase I to II. Like LPS, type 1 fimbriae largely
      increased the phase I attachment and the transformation ratio; however, they did
      not significantly influence the adhesion strength in phase II. CA had a negative
      effect on attachment in phases I and II by decreasing the adhered number of cells
      and the lateral detachment force, respectively, but had no influence on the
      transformation ratio.

PMID- 21842860
TI  - Multitarget structure-activity relationships characterized by activity-difference
      maps and consensus similarity measure.
AB  - Dual and triple activity-difference (DAD/TAD) maps are tools for the systematic
      characterization of structure-activity relationships (SAR) of compound data sets
      screened against two or three targets. DAD and TAD maps are two- and three-
      dimensional representations of the pairwise activity differences of compound data
      sets, respectively. Adding pairwise structural similarity information into these
      maps readily reveals activity cliff regions in the SAR for one, two, or three
      targets. In addition, pairs of compounds in the smooth regions of the SAR and
      scaffold hops are also easily identified in these maps. Herein, DAD and TAD maps
      are employed for the systematic characterization of the SAR of a benchmark set of
      299 compounds screened against dopamine, norepinephrine, and serotonin
      transporters. To reduce the well-known dependence of the activity landscape on
      the structural representation, five selected 2D and 3D structure representations
      were used to characterize the SAR. Systematic analysis of the DAD and TAD maps
      reveals regions in the landscape with similar SAR for two or the three targets as
      well as regions with inverse SAR, i.e., changes in structure that increase
      activity for one target, but decrease activity for the other target. Focusing the
      analysis on pairs of compounds with high structure similarity revealed the
      presence of single-, dual-, and triple-target activity cliffs, i.e., small
      changes in structure with high changes in potency for one, two, or the three
      targets, respectively. Triple-target scaffold hops are also discussed. Activity
      cliffs and scaffold hops were also quantified and represented using two recently
      proposed approaches namely, mean Structure Activity Landscape Index (mean SALI)
      and Consensus Structure-Activity Similarity (SAS) maps.

PMID- 21842861
TI  - Localization and speciation of arsenic in soil and desert plant Parkinsonia
      florida using MUXRF and MUXANES.
AB  - Parkinsonia florida is a plant species native to the semidesert regions of North
      America. The cultivation characteristics of this shrub/tree suggest that it could
      be used for phytoremediation purposes in semiarid regions. This work describes,
      through the use of synchrotron MUXRF and MUXANES techniques and ICP-OES, the
      arsenic (As) accumulation and distribution in P. florida plants grown in two
      soils spiked with As at 20 mg kg(-1). Plants grown in a sandy soil accumulated at
      least twice more As in the roots compared to plants grown in a loamy soil. The
      lower As accumulation in plants grown in the loamy soil corresponded to a lower
      concentration of As in the water-soluble fraction (WSF) of this soil. LC-ICP-MS
      speciation analysis showed only As(V) in the WSF from all treatments. In
      contrast, linear combination XANES speciation analysis from the root tissues
      showed As mainly present in the reduced As(III) form. Moreover, a fraction of the
      reduced As was found coordinating to S in a form consistent with As-Cys(3). The
      percentage of As coordinated to sulfur was smaller for plants grown in the loamy
      soil when compared to the sandy soil.

PMID- 21842862
TI  - PUB-MS: a mass spectrometry-based method to monitor protein-protein proximity in
      vivo.
AB  - The common techniques to study protein-protein proximity in vivo are not well
      adapted to the capabilities and the expertise of a standard proteomics
      laboratory, typically based on the use of mass spectrometry. With the aim of
      closing this gap, we have developed PUB-MS (for proximity utilizing biotinylation
      and mass spectrometry), an approach to monitor protein-protein proximity, based
      on biotinylation of a protein fused to a biotin-acceptor peptide (BAP) by a
      biotin-ligase, BirA, fused to its interaction partner. The biotinylation status
      of the BAP can be further detected by either Western analysis or mass
      spectrometry. The BAP sequence was redesigned for easy monitoring of the
      biotinylation status by LC-MS/MS. In several experimental models, we demonstrate
      that the biotinylation in vivo is specifically enhanced when the BAP- and BirA
      fused proteins are in proximity to each other. The advantage of mass spectrometry
      is demonstrated by using BAPs with different sequences in a single experiment
      (allowing multiplex analysis) and by the use of stable isotopes. Finally, we show
      that our methodology can be also used to study a specific subfraction of a
      protein of interest that was in proximity with another protein at a predefined
      time before the analysis.

PMID- 21842863
TI  - Synthesis and Diels-Alder cycloadditions of exo-imidazolidin-2-one dienes.
AB  - An efficient and versatile synthesis of novel exo-imidazolidin-2-one dienes is
      described. This involves the base-assisted condensation/cyclization cascade
      reaction of the monoimino derivatives of diacetyl with a series of isocyanates.
      This methodology enables preparation of symmetrical dienes, as long as the
      substrates have the same N substituent. Moreover, use of different N-substituted
      starting materials leads to formation of nonsymmetrical dienes. The reactivity of
      these dienes was evaluated in Diels-Alder reactions, showing a high reactivity.

PMID- 21842864
TI  - Conformation-dependent QSPR models: logPOW.
AB  - Quantitative structure-property relationships for predicting the water-octanol
      partition coefficient, logP(OW), are reported. The models are based on local
      properties calculated at the standard isodensity surface using semiempirical
      molecular orbital theory and use descriptors obtained as the areas of the surface
      found in each bin in a predefined binning scheme. The effect of conformation is
      taken into account but was found to have little effect on the predictive power of
      the models. A detailed error analysis suggests that the accuracy of the models is
      limited by that of the experimental data and that the best possible performance
      is approximately +/-0.5 log units. The models yield a local hydrophobicity
      function at the surface of the molecules.

PMID- 21842865
TI  - An n->pi* interaction in aspirin: implications for structure and reactivity.
AB  - Stereoelectronic effects modulate molecular structure, reactivity, and
      conformation. We find that the interaction between the ester and carboxyl
      moieties of aspirin has a previously unappreciated quantum mechanical character
      that arises from the delocalization of an electron pair (n) of a donor group into
      the antibonding orbital (pi*) of an acceptor group. This interaction affects the
      physicochemical attributes of aspirin and could have implications for its
      pharmacology.

PMID- 21842866
TI  - Discrimination between Shiraz wines from different Australian regions: the role
      of spectroscopy and chemometrics.
AB  - This study reports the use of UV-visible (UV-vis), near-infrared (NIR), and
      midinfrared (MIR) spectroscopy combined with chemometrics to discriminate among
      Shiraz wines produced in five Australian regions. In total, 98 commercial Shiraz
      samples (vintage 2006) were analyzed using UV-vis, NIR, and MIR wavelength
      regions. Spectral data were interpreted using principal component analysis (PCA),
      linear discriminant analysis (LDA), and soft independent model of class analogy
      (SIMCA) to classify the wine samples according to region. The results indicated
      that wine samples from Western Australia and Coonawarra can be separated from the
      other wines based on their MIR spectra. Classification results based on MIR
      spectra also indicated that LDA achieved 73% overall correct classification,
      while SIMCA 95.3%. This study demonstrated that IR spectroscopy combined with
      chemometric methods can be a useful tool for wine region discrimination.

PMID- 21842867
TI  - Gold nano-popcorn attached SWCNT hybrid nanomaterial for targeted diagnosis and
      photothermal therapy of human breast cancer cells.
AB  - Breast cancer presents greatest challenge in health care in today's world. The
      key to ultimately successful treatment of breast cancer disease is an early and
      accurate diagnosis. Current breast cancer treatments are often associated with
      severe side effects. Driven by the need, we report the design of novel hybrid
      nanomaterial using gold nano popcorn-attached single wall carbon nanotube for
      targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human
      breast cancer cell sensing have been performed in 10 cancer cells/mL level, using
      surface enhanced Raman scattering of single walls carbon nanotube's D and G
      bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS
      assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and
      it will be able to distinguish it from other non targeted MDA-MB breast cancer
      cell line and HaCaT normal skin cell line. Our results also show that 10 min of
      photothermal therapy treatment by 1.5 W/cm(2) power, 785 nm laser is enough to
      kill cancer cells very effectively using S6 aptamer attached hybrid
      nanomaterials. Possible mechanisms for targeted sensing and operating principle
      for highly efficient photothermal therapy have been discussed. Our experimental
      results reported here open up a new possibility for using aptamers modified
      hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell
      lines quickly.

PMID- 21842868
TI  - Understanding the errors of SHAPE-directed RNA structure modeling.
AB  - Single-nucleotide-resolution chemical mapping for structured RNA is being rapidly
      advanced by new chemistries, faster readouts, and coupling to computational
      algorithms. Recent tests have shown that selective 2'-hydroxyl acylation by
      primer extension (SHAPE) can give near-zero error rates (0-2%) in modeling the
      helices of RNA secondary structure. Here, we benchmark the method using six
      molecules for which crystallographic data are available: tRNA(phe) and 5S rRNA
      from Escherichia coli, the P4-P6 domain of the Tetrahymena group I ribozyme, and
      ligand-bound domains from riboswitches for adenine, cyclic di-GMP, and glycine.
      SHAPE-directed modeling of these highly structured RNAs gave an overall false
      negative rate (FNR) of 17% and a false discovery rate (FDR) of 21%, with at least
      one helix prediction error in five of the six cases. Extensive variations of data
      processing, normalization, and modeling parameters did not significantly mitigate
      modeling errors. Only one varation, filtering out data collected with
      deoxyinosine triphosphate during primer extension, gave a modest improvement (FNR
      = 12%, and FDR = 14%). The residual structure modeling errors are explained by
      the insufficient information content of these RNAs' SHAPE data, as evaluated by a
      nonparametric bootstrapping analysis. Beyond these benchmark cases, bootstrapping
      suggests a low level of confidence (<50%) in the majority of helices in a
      previously proposed SHAPE-directed model for the HIV-1 RNA genome. Thus, SHAPE
      directed RNA modeling is not always unambiguous, and helix-by-helix confidence
      estimates, as described herein, may be critical for interpreting results from
      this powerful methodology.

PMID- 21842869
TI  - Clay-mediated synthesis of silver nanoparticles exhibiting low-temperature
      melting.
AB  - Nanohybrids of silver nanoparticles (AgNPs) supported on mica clay were
      synthesized by in situ reduction of silver nitrate in an aqueous solution. The
      required mica platelets of high aspect ratio were previously prepared by the
      exfoliation of mica clay stacks in a multilayered structure through an ionic
      exchange reaction with poly(oxypropylene)-amine-salt. The exfoliated nanoscale
      mica platelets (Mica) are polydispersed such that each platelet is 300-1000 nm in
      width and 1 nm in thickness. These platelets possess ionic charges in the form of
      =SiO(-)Na(+) at 120 mequiv/100 g and are suitable for supporting AgNPs in the
      process of in situ reduction of silver nitrate. Transmission electronic
      microscopy revealed the formation of AgNPs with a narrow size distribution of ca.
      8 nm in diameter on the rim of individual Mica platelets. However, the pristine
      layered Mica structure without exfoliation failed to produce a fine AgNP
      distribution but instead generated particles larger than 30 nm and some
      precipitates. Characterization by differential scanning calorimetry and field
      emission scanning electron microscopy revealed that the fine AgNPs on Mica
      platelets exhibited a low melting temperature of 110  degrees C. The AgNP/Mica
      nanohybrid not containing an organic dispersant is considered to be a "naked"
      silver particle.

PMID- 21842870
TI  - Sustained release of transgenic human factor IX: preparation, characterization,
      and in vivo efficacy.
AB  - The current regimen of factor IX (FIX) injection is of an episodic format, which
      leads to limited efficacy. A sustained release dosage form is beneficial in terms
      of reducing the injection frequency and improving the therapeutic effectiveness.
      The aim of this study was to formulate a new microsphere form of a FIX-containing
      preparation to diminish these shortcomings. Using the water-in-oil-in-water
      (W/O/W) double emulsion technique, injectable long-acting FIX microspheres were
      prepared with transgenic recombinant human FIX (rhFIX) and poly(lactic-co
      glycolic acid) (PLGA) polymer. The rhFIX microspheres prepared had diameters
      ranging between 25-350 MUm and easily passed through a small-gauge-number needle
      for subcutaneous injection. In in vitro release testing, the microspheres had a
      sustained release profile featuring an initial burst and sustained release
      spanning a 5-day period. In in vivo pharmacodynamic testing, normalization of the
      bleeding of hemophilic mice was maintained for 5 days with microsphere injection
      as compared with 2 days with native rhFIX. Taken together, these results
      indicated that long-acting FIX microspheres were successfully prepared for
      potential use in hemophilic prophylaxis.

PMID- 21842871
TI  - Nanoseeding via dual surface modification of alkyl monolayer for site-controlled
      electroless metallization.
AB  - In this work, an attempt to fabricate nanostructured metallization patterns on
      SiO(2) dielectric layers is made by using plasma-patterned self-assembled
      monolayers (SAMs), in conjunction with a novel aqueous seeding and electroless
      process. Taking octadecyltrichlorosilane (OTS) as a test material, the authors
      demonstrate that optimizing the N(2)-H(2) plasma conditions leads to the
      successive conversion of the topmost aliphatic chains of alkyl SAMs to carboxyl
      (COOH) and hydroxyl (C-OH) functional groups, which was previously found in alkyl
      SAMs only by exposure to "oxygen-based" plasma. Further modifying the plasma
      exposed (either COOH or C-OH terminated) regions with an aqueous solution (SC-1)
      creates surface functionalities that are viable for site-controlled metallic
      seeding (e.g., Co or Ni) with an adsorption selectivity of greater than 1000:1.
      Neither the combination of costly PdCl(2) and complex additives nor the demerits
      of the associated aqueous chemistry (e.g., seed agglomeration and seed
      sparseness) are involved. Therefore, the seed particles are only 3 nm in size.
      Simultaneously, there are sufficient particle densities previously unattainable
      for electroless deposition to trigger highly resolved Cu metallization patterns
      with a film thickness of less than 10 nm. The formation of the seed-adsorbing
      sites is discussed, based on a plasma-dissociated, water-mediated chemical
      oxidation route.

PMID- 21842872
TI  - Spin control in oxamato-based manganese(II)-copper(II) coordination polymers with
      brick-wall layer architectures.
AB  - Two new heterobimetallic manganese(II)-copper(II) coordination polymers of
      formulas [Mn(2)Cu(2)(Me(3)mpba)(2)(H(2)O)(6)].8H(2)O (1) and
      [Mn(2)Cu(2)(Me(4)ppba)(2)(H(2)O)(6)].8H(2)O (2) [Me(3)mpba = 2,4,6-trimethyl-N,N'
      1,3-phenylenebis(oxamate) and Me(4)ppba = 2,3,5,6-tetramethyl-N,N'-1,4
      phenylenebis(oxamate)] have been synthesized following a molecular-programmed
      self-assembly method from the corresponding dicopper(II) complexes acting as
      metalloligands toward Mn(II) ions. 1 and 2 consist of neutral Mn(II)(2)Cu(II)(2)
      layers with a brick-wall structure made up of oxamato-bridged Mn(II)Cu(II) chains
      connected through double meta- (1) and para-substituted (2) permethylated
      phenylene spacers. Overall magnetic (1) and nonmagnetic (2) layer ground states
      result from the ferro- and antiferromagnetic interchain interactions between the
      oxamato-bridged Mn(II)Cu(II) ferrimagnetic chains across m- and p-phenylene
      spacers, respectively. Interestingly, compound 1 exhibits a long-range
      ferromagnetic ordering with a rather high Curie temperature (T(C)) of 20.0 K.

PMID- 21842873
TI  - Nucleophilic addition of sulfonamides to bromoacetylenes: facile preparation of
      pyrroles.
AB  - Nucleophilic addition of sulfonamides to 1-bromo-1-alkynes provided (Z)-N-(1
      bromo-1-alken-2-yl)-p-toluenesulfonamides in good yield and in a highly regio-
      and stereoselective manner. Treatment of product (Z)-N-(1-bromo-1-octen-2-yl)-N
      allyl-p-toluenesulfonamide with a palladium catalyst under Heck conditions
      afforded 1-(p-toluenesulfonyl)-2-hexyl-4-methylpyrrole in good yield. Other
      pyrroles with various substituents can also be prepared in good yield by this
      method.

PMID- 21842874
TI  - Activation-dependent adsorption of cytokines and toxins related to liver failure
      to carbon beads.
AB  - In the course of severe pathological conditions, such as acute liver failure and
      sepsis, toxic metabolites and mediators of inflammation are released into the
      patient's circulation. One option for the supportive treatment of these
      conditions is plasmapheresis, in which plasma, after being separated from the
      cellular components of the blood, is cleansed by adsorption of harmful molecules
      on polymers or activated carbon. In this work, the adsorption characteristics of
      activated carbon beads with levels of activation ranging from 0 to 86% were
      assessed for both hydrophobic compounds accumulating in liver failure (bilirubin,
      cholic acid, phenol and tryptophan) and cytokines (tumor necrosis factor alpha
      and interleukin-6). Progressive activation resulted in significant gradual
      reduction of both bulk density and mean particle size, in an increase in the
      specific surface area, and to changes in pore size distribution with progressive
      broadening of micropores. These structural changes went hand in hand with
      enhanced adsorption of small adsorbates, such as IL-6 and cholic acid and, to a
      lesser extent, also of large molecules, such as TNF-alpha.

PMID- 21842876
TI  - Argiotoxin in the closed AMPA receptor channel: experimental and modeling study.
AB  - Binding of argiotoxin in the closed state of Ca(2+)-permeable AMPA receptor
      channels was studied using electrophysiological and molecular modeling
      approaches. Experimental study unambiguously revealed that argiotoxin is trapped
      in the closed AMPA receptor channels after agonist dissociation. Docking of the
      argiotoxin to the channel model based on recently published X-ray structure
      demonstrated that the drug can be effectively accommodated in the cavity of the
      closed channel only if the terminal moiety of the molecule penetrates in the
      narrow portion of the pore below the selectivity filter. Combining these results,
      we conclude that the selectivity filter of the AMPA receptor channels is not
      sterically occluded in the closed state.

PMID- 21842875
TI  - Characterization of noninnocent metal complexes using solid-state NMR
      spectroscopy: o-dioxolene vanadium complexes.
AB  - (51)V solid-state NMR (SSNMR) studies of a series of noninnocent vanadium(V)
      catechol complexes have been conducted to evaluate the possibility that (51)V NMR
      observables, quadrupolar and chemical shift anisotropies, and electronic
      structures of such compounds can be used to characterize these compounds. The
      vanadium(V) catechol complexes described in these studies have relatively small
      quadrupolar coupling constants, which cover a surprisingly small range from 3.4
      to 4.2 MHz. On the other hand, isotropic (51)V NMR chemical shifts cover a wide
      range from -200 to 400 ppm in solution and from -219 to 530 ppm in the solid
      state. A linear correlation of (51)V NMR isotropic solution and solid-state
      chemical shifts of complexes containing noninnocent ligands is observed. These
      experimental results provide the information needed for the application of (51)V
      SSNMR spectroscopy in characterizing the electronic properties of a wide variety
      of vanadium-containing systems and, in particular, those containing noninnocent
      ligands and that have chemical shifts outside the populated range of -300 to -700
      ppm. The studies presented in this report demonstrate that the small quadrupolar
      couplings covering a narrow range of values reflect the symmetric electronic
      charge distribution, which is also similar across these complexes. These
      quadrupolar interaction parameters alone are not sufficient to capture the rich
      electronic structure of these complexes. In contrast, the chemical shift
      anisotropy tensor elements accessible from (51)V SSNMR experiments are a highly
      sensitive probe of subtle differences in electronic distribution and orbital
      occupancy in these compounds. Quantum chemical (density functional theory)
      calculations of NMR parameters for [VO(hshed)(Cat)] yield a (51)V chemical shift
      anisotropy tensor in reasonable agreement with the experimental results, but
      surprisingly the calculated quadrupolar coupling constant is significantly
      greater than the experimental value. The studies demonstrate that substitution of
      the catechol ligand with electron-donating groups results in an increase in the
      HOMO-LUMO gap and can be directly followed by an upfield shift for the vanadium
      catechol complex. In contrast, substitution of the catechol ligand with electron
      withdrawing groups results in a decrease in the HOMO-LUMO gap and can directly be
      followed by a downfield shift for the complex. The vanadium catechol complexes
      were used in this work because (51)V is a half-integer quadrupolar nucleus whose
      NMR observables are highly sensitive to the local environment. However, the
      results are general and could be extended to other redox-active complexes that
      exhibit coordination chemistry similar to that of the vanadium catechol
      complexes.

PMID- 21842877
TI  - Memory effects on adsorption tubes for mercury vapor measurement in ambient air:
      elucidation, quantification, and strategies for mitigation of analytical bias.
AB  - The short- and long-term memory effects associated with measurements of mercury
      vapor in air using gold-coated silica adsorption tubes have been described. Data
      are presented to quantify these effects and to determine their dependence on
      certain relevant measurement parameters, such as number of heating cycles used
      for each analysis, age of adsorption tube, mass of mercury on adsorption tube,
      and the length of time between analyses. The results suggest that the long-term
      memory effect is due to absorption of mercury within the bulk gold in the
      adsorption tube, which may only be fully liberated by allowing enough time for
      this mercury to diffuse to the gold surface. The implications of these effects
      for air quality networks making these measurements routinely has been discussed,
      and recommendations have been made to ensure any measurement bias is minimized.

PMID- 21842878
TI  - A molecular half-wave rectifier.
AB  - This paper describes the performance of junctions based on self-assembled
      monolayers (SAMs) as the functional element of a half-wave rectifier (a simple
      circuit that converts, or rectifies, an alternating current (AC) signal to a
      direct current (DC) signal). Junctions with SAMs of 11-(ferrocenyl)-1
      undecanethiol or 11-(biferrocenyl)-1-undecanethiol on ultraflat, template
      stripped Ag (Ag(TS)) bottom electrodes, and contacted by top electrodes of
      eutectic indium-gallium (EGaIn), rectified AC signals, while similar junctions
      based on SAMs of 1-undecanethiol-SAMs lacking the ferrocenyl terminal group-did
      not. SAMs in these AC circuits (operating at 50 Hz) remain stable over a larger
      window of applied bias than in DC circuits. AC measurements, therefore, can
      investigate charge transport in SAM-based junctions at magnitudes of bias
      inaccessible to DC measurements. For junctions with SAMs of alkanethiols,
      combining the results from AC and DC measurements identifies two regimes of bias
      with different mechanisms of charge transport: (i) low bias (|V| < 1.3 V), at
      which direct tunneling dominates, and (ii) high bias (|V| > 1.3 V), at which
      Fowler-Nordheim (FN) tunneling dominates. For junctions with SAMs terminated by
      Fc moieties, the transition to FN tunneling occurs at |V| ~ 2.0 V. Furthermore,
      at sufficient forward bias (V > 0.5 V), hopping makes a significant contribution
      to charge transport and occurs in series with direct tunneling (V ? 2.0 V) until
      FN tunneling activates (V ? 2.0 V). Thus, for Fc-terminated SAMs at forward bias,
      three regimes are apparent: (i) direct tunneling (V = 0-0.5 V), (ii) hopping plus
      direct tunneling (V ~ 0.5-2.0 V), and (iii) FN tunneling (V ? 2.0 V). Since
      hopping does not occur at reverse bias, only two regimes are present over the
      measured range of reverse bias. This difference in the mechanisms of charge
      transport at forward and reverse bias for junctions with Fc moieties resulted in
      large rectification ratios (R > 100) and enabled half-wave rectification.

PMID- 21842879
TI  - Application of synchrotron microprobe methods to solid-phase speciation of metals
      and metalloids in house dust.
AB  - Determination of the source and form of metals in house dust is important to
      those working to understand human and particularly childhood exposure to metals
      in residential environments. We report the development of a synchrotron
      microprobe technique for characterization of multiple metal hosts in house dust.
      We have applied X-ray fluorescence for chemical characterization and X-ray
      diffraction for crystal structure identification using microfocused synchrotron X
      rays at a less than 10 MUm spot size. The technique has been evaluated by
      application to archived house dust samples containing elevated concentrations of
      Pb, Zn, and Ba in bedroom dust, and Pb and As in living room dust. The technique
      was also applied to a sample of soil from the corresponding garden to identify
      linkages between indoor and outdoor sources of metals. Paint pigments including
      white lead (hydrocerussite) and lithopone (wurtzite and barite) are the primary
      source of Pb, Zn, and Ba in bedroom dust, probably related to renovation activity
      in the home at the time of sampling. The much lower Pb content in the living room
      dust shows a relationship to the exterior soil and no specific evidence of Pb and
      Zn from the bedroom paint pigments. The technique was also successful at
      confirming the presence of chromated copper arsenate treated wood as a source of
      As in the living room dust. The results of the study have confirmed the utility
      of this approach in identifying specific metal forms within the dust.

PMID- 21842880
TI  - Advances in surface plasmon resonance sensing with nanoparticles and thin films:
      nanomaterials, surface chemistry, and hybrid plasmonic techniques.
AB  - Nanomaterials developed for localized surface plasmon resonance (LSPR) are
      increasingly integrated to classical prism-based SPR sensors, providing enhanced
      sensitivity and lower detection limits. The unique properties of these novel
      nanomaterials in addition to novel surface chemistry to minimize nonspecific
      adsorption and surface plasmon-coupled techniques with other spectroscopic or
      mass spectrometry techniques are highlighted in this article.

PMID- 21842881
TI  - From NMR relaxation to fractional Brownian dynamics in proteins: results from a
      virtual experiment.
AB  - In a recent simulation study [J. Chem. Phys. 2010, 133, 145101], it has been
      shown that the time correlation functions probed by nuclear magnetic resonance
      (NMR) relaxation spectroscopy of proteins are well described by a fractional
      Brownian dynamics model, which accounts for the wide spectrum of relaxation rates
      characterizing their internal dynamics. Here, we perform numerical experiments to
      explore the possibility of using this model directly in the analysis of
      experimental NMR relaxation data. Starting from a molecular dynamics simulation
      of the 266 residue protein 6PGL in explicit water, we construct virtual (15)N
      R(1), R(2), and NOE relaxation rates at two different magnetic fields, including
      artificial noise, and test how far the parameters obtained from a fit of the
      model to the virtual experimental data coincide with those obtained from an
      analysis of the MD time correlation functions that have been used to construct
      these data. We show that in most cases, close agreement is found. Acceptance or
      rejection of parameter values obtained from relaxation rates are discussed on a
      physical basis, therefore avoiding overfitting.

PMID- 21842882
TI  - Bistable charge configuration of donor systems near the GaAs(110) surfaces.
AB  - In gated semiconductor devices, the space charge layer that is located under the
      gate electrode acts as the functional element. With increasing gate voltage, the
      microscopic process forming this space charge layer involves the subsequent
      ionization or electron capture of individual dopants within the semiconductor. In
      this Letter, a scanning tunneling microscope tip is used as a movable gate above
      the (110) surface of n-doped GaAs. We study the build-up process of the space
      charge region considering donors and visualize the charge states of individual
      and multi donor systems. The charge configuration of single donors is determined
      by the position of the tip and the applied gate voltage. In contrast, a two donor
      system with interdonor distances smaller than 10 nm shows a more complex
      behavior. The electrostatic interaction between the donors in combination with
      the modification of their electronic properties close to the surface results in
      ionization gaps and bistable charge switching behavior.

PMID- 21842883
TI  - Quantitative label-free characterization of avidin-biotin assemblies on silanized
      glass.
AB  - In this study, a time-of-flight secondary ion mass spectrometer TOF-SIMS,
      operating in the event-by-event bombardment/detection mode was used to
      characterize avidin-biotin assemblies on silane-modified glass substrates. SIMS
      was used to analyze several variants of the biointerface, including avidin
      physically adsorbed on a monofunctional acryl silane surface and covalently
      attached on monofunctional (amine terminated) and bifunctional (amine and acryl
      terminated) silanes. The goal of these studies was to determine density of avidin
      and biotin layers chemically or physically adsorbed on silanized glass substrate.
      An individual impact of a C(60) projectile used in this study creates a
      hemispherical crater (~10 nm in diameter) and emits large numbers of secondary
      ions from the same nanovolume. Thus, a single impact enables one to unfold
      distinct secondary ions that span the thickness of the assembled film. This
      method was used to monitor the presence of glass, silane, and protein ions and to
      estimate the thickness and density of the avidin layer. In addition, we employed
      the double coincidence mass spectrometry approach to identify ions coemitted from
      a specific stratum of the biointerface. This approach was used to determine
      density of biotin and avidin immobilization while eliminating interferences from
      isobaric ions that originated from other constituents on the surface. Overall,
      novel TOF-SIMS quantitative approaches employed here were useful for examining
      complex biointerfaces and determining both lateral and in depth composition of
      the film.

PMID- 21842884
TI  - Metabolomic analysis of Ranunculus spp. as potential agents involved in the
      etiology of equine grass sickness.
AB  - Identification of toxic or harmful agents continues to be a key goal in
      agricultural chemistry. This paper reports a metabolomic analysis of Ranunculus
      repens and related species, which were recently postulated to be cocausative
      agents in the etiology of equine grass sickness (EGS). Specifically, samples
      collected at EGS sites were compared with those from non-EGS sites. Furthermore,
      interspecific and seasonal variations and the species' response to edaphic and
      climatic factors were investigated. (1)H NMR spectroscopy in combination with
      multivariate data analysis was applied to the crude methanol extracts of the
      Ranunculus samples, as well as their chloroform fractions. Samples from EGS sites
      were significantly different from control samples. The metabolite composition
      varied greatly between different Ranunculus species. No significant changes could
      be observed between samples collected in different seasons. This work provides
      strong evidence that Ranunculus is involved in the etiology of EGS and has
      implications for agricultural management of pastures.

PMID- 21842886
TI  - Localized electron transfer and the effect of tunneling on the rates of
      Ru(bpy)3(2+) oxidation and reduction as measured by scanning electrochemical
      microscopy.
AB  - The kinetics of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)) oxidation and
      reduction in acetonitrile were investigated by steady-state voltammetry using
      scanning electrochemical microscopy (SECM). The SECM setup was placed inside a
      drybox for carrying out experiments in an anhydrous atmosphere and in the absence
      of oxygen. The standard rate constant, k degrees , for Ru(bpy) oxidation at a Pt
      electrode (radius, a = 5 MUm) was 0.7 +/- 0.1 cm/s, which is smaller than k
      degrees  for Ru(bpy) reduction measured under the same conditions (>=3 cm/s).
      This is attributed to the 2,2'-bipyridine ligands having an electron-transfer
      (ET) blocking effect on the oxidation of the ruthenium(II) center, as opposed to
      the reduction, which involves ET to the exposed ligands. Thus, tunneling effects
      may be important in considering the ET in this molecule.

PMID- 21842885
TI  - Polyamines are traps for reactive intermediates in furan metabolism.
AB  - Furan is toxic and carcinogenic in rodents. Because of the large potential for
      human exposure, furan is classified as a possible human carcinogen. The detailed
      mechanism by which furan causes toxicity and cancer is not yet known. Since furan
      toxicity requires cytochrome P450-catalyzed oxidation of furan, we have
      characterized the urinary and hepatocyte metabolites of furan to gain insight
      into the chemical nature of the reactive intermediate. Previous studies in
      hepatocytes indicated that furan is oxidized to the reactive alpha,beta
      unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), which reacts with
      glutathione (GSH) to form 2-(S-glutathionyl)succinaldehyde (GSH-BDA). This
      intermediate forms pyrrole cross-links with cellular amines such as lysine and
      glutamine. In this article, we demonstrate that GSH-BDA also forms cross-links
      with ornithine, putrescine, and spermidine when furan is incubated with rat
      hepatocytes. The relative levels of these metabolites are not completely
      explained by hepatocellular levels of the amines or by their reactivity with GSH
      BDA. Mercapturic acid derivatives of the spermidine cross-links were detected in
      the urine of furan-treated rats, which indicates that this metabolic pathway
      occurs in vivo. Their detection in furan-treated hepatocytes and in urine from
      furan-treated rats indicates that polyamines may play an important role in the
      toxicity of furan.

PMID- 21842887
TI  - Selective mono- to perarylations of tetrabromothiophene by a cyclobutene-1,2
      diylbisimidazolium preligand.
AB  - (Cyclobut-1-ene-1,2-diyl)bis(1-methylimidazolium)tetrafluoroborate is applied as
      preligand in palladium-catalyzed cross-coupling reactions starting from
      tetrabromothiophene for the synthesis of mono-, bi-, tri-, and tetraaryl
      substituted thiophenes bearing up to four different aryl rings. A synthetic kit
      for preparations of nine different substitution patterns of arylated thiophenes
      is presented by application of only one single catalyst system. In agreement with
      DFT calculations, which predict energetically low rotational barriers in triaryl
      3-bromothiophenes and tetraarylthiophenes, no NOE effects between adjacent aryl
      rings are detectable. The regioselectivity of their syntheses has therefore been
      elucidated by reduction of triaryl-3-bromothiophene to 2,3,5-triarylthiophene
      followed by HMBC, HSQC, and NOESY NMR measurements. Additionally, results of an X
      ray single structure analysis are presented.

PMID- 21842888
TI  - Impacts of climate and feeding conditions on the annual accumulation (1986-2009)
      of persistent organic pollutants in a terrestrial raptor.
AB  - The relationships between climate variability, feeding conditions, and the annual
      accumulation of polychlorinated biphenyls (PCB), 1,1-dichloro-2,2-bis (p
      chlorophenyl) ethylene (p,p'-DDE) and polybrominated diphenyl ethers (PBDE) in
      eggs (n = 168) of tawny owls (Strix aluco) were assessed over a 24-year period
      (1986-2009) in Central Norway. Winter climate variables included the North
      Atlantic Oscillation (NAO) and snow conditions, whereas feeding conditions were
      assessed using vole abundance. The concentrations of all compounds declined
      between 79% (p,p'-DDE) and 86% (PBDE) over the time period. For PCB and p,p'-DDE,
      the accumulation was positively associated with snow depth, and negatively
      associated with NAO (i.e., high accumulation in cold and dry winters) when vole
      abundance was low, suggesting trade-offs between winter severity and feeding
      conditions. That is, females mobilize more body fat reserves in cold winters when
      feeding conditions are poor, which results in increased circulating contaminant
      concentrations and maternal transfer to the eggs. Owls may also have been forced
      to feed on prey with higher contaminant loads due to restricted prey
      availability. For the recently banned PBDEs, the accumulation was high when NAO
      was low, while snow depth was positively associated with PBDE accumulation only
      when feeding conditions were good. This suggests somewhat different dynamics of
      PBDE in the environment or in the owls, compared to PCB and p,p'-DDE. However,
      climate and feeding conditions explained as much of the annual variation in
      concentrations of all POPs, as the overall decreasing trend over the 24 years.
      Hence, such factors should be considered in monitoring programs for POPs.
      Moreover, to better understand the mechanisms of climate effects on POP
      accumulation, future studies should measure pollutants in different components of
      the food chain.

PMID- 21842889
TI  - Challenges to modeling "cold pool" meteorology associated with high pollution
      episodes.

PMID- 21842890
TI  - A reactive Ru-binaphtholate building block with self-tuning hapticity.
AB  - A versatile Ru-BINO building block is reported, which offers a straightforward
      entry point into the chemistry of atropisomeric binaphtholate complexes of
      ruthenium. Reaction of RuCl(2)(PPh(3))(3)6a with Tl(2)((S)-BINO) affords Ru((S)
      BINO)(PPh(3))(2)7 as a mixture of isomers: in 7', the BINO ligand is bound via
      eta(3)-CCO,eta(1)-O' donors, and in symmetrical 7", via eta(3)-CCO,eta(3)-O'C'C'
      interactions. The bis(enolate) BINO bonding mode in the latter, not previously
      observed for any metal, underscores the remarkable geometric and electronic
      flexibility of the binaphtholate moiety. The BINO ligand proves able to stabilize
      complexes containing as few as two, and as many as four, additional ligands in 7
      and its derivatives, enabling a synthetic versatility that contrasts with that of
      the superficially similar o-catecholate complex Ru(o-cat)(PPh(3))(3). As with the
      important achiral Ru precursor 6a, complex 7 undergoes facile transformation into
      a range of products under mild conditions, including acetonitrile, pyridine, and
      vinylidene derivatives. Single-crystal X-ray structures are reported for three of
      these complexes: Ru(eta(3),eta(3)-(S)-BINO)(PPh(3))(2)7", Ru(eta(3),eta(1)-(S)
      BINO)(PPh(3))(2)(MeCN) 9, and Ru(eta(3),eta(1)-(S)-BINO)(PPh(3))(py)(2)11.
      (13)C{(1)H} NMR signatures are proposed for new and known BINO coordination modes
      (eta(1)-O,eta(1)-O'; eta(1)-C1,eta(1)-O'; eta(3)-CCO,eta(3)-O'C'C'; eta(3)
      CCO,eta(1)-O'; eta(6)-C(6),eta(1)-O'), as a potential aid to further developments
      in late-metal BINO chemistry.

PMID- 21842891
TI  - Spiral superstructures of amyloid-like fibrils of polyglutamic acid: an infrared
      absorption and vibrational circular dichroism study.
AB  - Amyloid fibrils, which are often associated with certain degenerative disorders,
      reveal a number of intriguing spectral properties. However, the relationship
      between the structure of fibrils and their optical traits remains poorly
      understood. Poly(L-glutamic) acid is a model polypeptide shown recently to form
      amyloid-like fibrils with an atypical infrared amide I' band at 1595 cm(-1),
      which has been attributed to the presence of bifurcated hydrogen bonds coupling
      C?O and N-D groups of the main chains to glutamate side chains. Here we show that
      this unusual amide I' band is observed only for fibrils grown from pure
      enantiomers of the polypeptide, whereas fibrils precipitating from equimolar
      mixtures of poly(L-glutamic) and poly(D-glutamic) acids have amide I' bands at
      1684 and 1612 cm(-1), which are indicative of a typical intermolecular
      antiparallel beta-sheet. Pure enantiomers of polyglutamic acid form spirally
      twisted superstructures whose handedness is correlated to the amino acid
      chirality, while fibrils prepared from the racemate do not form scanning electron
      microscopy (SEM)-detectable mesoscopically ordered structures. Vibrational
      circular dichroism (VCD) spectra of beta-aggregates prepared from mixtures of all
      L- or D-polyglutamic acid in varying ratios indicate that the enhancement of VCD
      intensity correlates with the presence of the twisted superstructures. Our
      results demonstrate that both IR absorption and enhanced VCD are sensitive to
      subtle packing defects taking place within the compact structure of amyloid
      fibrils.

PMID- 21842892
TI  - Probing the role of chain length on the diffusion dynamics of pi-conjugated
      polymers by fluorescence correlation spectroscopy.
AB  - We investigate the role of the chain length and molecular weight distribution on
      the diffusion dynamics of freshly synthesized MEH-PPV polymer chains. For the
      above purpose, a new technique based on combination of size exclusion
      chromatography (SEC) with fluorescence correlation spectroscopy (FCS) is
      developed to probe the diffusion dynamics of a narrow molecular weight
      distribution of fractionated samples of 20-500 kDa. The narrow dispersed samples
      were characterized by absorbance, emission, and time-resolved fluorescence decay
      techniques. The results revealed that the properties of fractionated samples were
      almost uniform for a wide range of molecular weights. A maximum entropy based
      method for FCS data analysis is employed to obtain the correct diffusion
      coefficients of the polymer chains with heterogeneous dynamics. The FCS
      experiment on the unfractionated broad molecular weight sample is not enough to
      establish the correlation between the molecular weight of the chains with
      diffusion dynamics and emphasized the need for relatively monodispersed pi
      conjugated polymers. FCS results show that higher molecular weight chains diffuse
      much faster than shorter ones. Atomic force microscopy revealed that 300 kDa
      polymers produced 130 nm particles, whereas 50 kDa polymer chains formed
      micrometer size aggregates. At higher molecular weights, the strong chain
      interactions promote the formation of globular (or tightly packed) particles
      which diffuse faster in solution. The low molecular weight chains experience
      strong interparticle interaction; as a consequence, the diffusion of chains
      becomes slower. In the present investigation, we demonstrate the need for the
      narrow polydisperse sample for establishing the correlation between diffusion
      dynamics and chain length (or molecular weights) of pi-conjugated polymers using
      a single molecule spectroscopy technique such as FCS.

PMID- 21842894
TI  - Protein-ligand interaction energies with dispersion corrected density functional
      theory and high-level wave function based methods.
AB  - With dispersion-corrected density functional theory (DFT-D3) intermolecular
      interaction energies for a diverse set of noncovalently bound protein-ligand
      complexes from the Protein Data Bank are calculated. The focus is on major
      contacts occurring between the drug molecule and the binding site. Generalized
      gradient approximation (GGA), meta-GGA, and hybrid functionals are used. DFT-D3
      interaction energies are benchmarked against the best available wave function
      based results that are provided by the estimated complete basis set (CBS) limit
      of the local pair natural orbital coupled-electron pair approximation (LPNO
      CEPA/1) and compared to MP2 and semiempirical data. The size of the complexes and
      their interaction energies (DeltaE(PL)) varies between 50 and 300 atoms and from 
      1 to -65 kcal/mol, respectively. Basis set effects are considered by applying
      extended sets of triple- to quadruple-zeta quality. Computed total DeltaE(PL)
      values show a good correlation with the dispersion contribution despite the fact
      that the protein-ligand complexes contain many hydrogen bonds. It is concluded
      that an adequate, for example, asymptotically correct, treatment of dispersion
      interactions is necessary for the realistic modeling of protein-ligand binding.
      Inclusion of the dispersion correction drastically reduces the dependence of the
      computed interaction energies on the density functional compared to uncorrected
      DFT results. DFT-D3 methods provide results that are consistent with LPNO-CEPA/1
      and MP2, the differences of about 1-2 kcal/mol on average (<5% of DeltaE(PL))
      being on the order of their accuracy, while dispersion-corrected semiempirical
      AM1 and PM3 approaches show a deviating behavior. The DFT-D3 results are found to
      depend insignificantly on the choice of the short-range damping model. We propose
      to use DFT-D3 as an essential ingredient in a QM/MM approach for advanced virtual
      screening approaches of protein-ligand interactions to be combined with similarly
      "first-principle" accounts for the estimation of solvation and entropic effects.

PMID- 21842893
TI  - In vitro cellular uptake and dimerization of signal transducer and activator of
      transcription-3 (STAT3) identify the photosensitizing and imaging-potential of
      isomeric photosensitizers derived from chlorophyll-a and bacteriochlorophyll-a.
AB  - Among the photosensitizers investigated, both ring-D and ring-B reduced chlorins
      containing the m-iodobenzyloxyethyl group at position-3 and a carboxylic acid
      functionality at position-17(2) showed the highest uptake by tumor cells and
      light-dependent photoreaction that correlated with maximal tumor-imaging
      [positron emission tomography (PET) and fluorescence] and long-term photodynamic
      therapy (PDT) efficacy in BALB/c mice bearing Colon26 tumors. However, among the
      ring-D reduced compounds, the isomer containing the 1'-m-iobenzyloxyethyl group
      at position-3 was more effective than the corresponding 8-(1'-m
      iodobenzyloxyethyl) derivative. All photosensitizers showed maximum uptake by
      tumor tissue 24 h after injection, and the tumors exposed with light at low
      fluence and fluence rates (128 J/cm(2), 14 mW/cm(2)) produced significantly
      enhanced tumor eradication than those exposed at higher fluence and fluence rate
      (135 J/cm(2), 75 mW/cm(2)). Interestingly, dose-dependent cellular uptake of the
      compounds and light-dependent STAT3 dimerization have emerged as sensitive rapid
      indicators for PDT efficacy in vitro and in vivo and could be used as in vitro/in
      vivo biomarkers for evaluating and optimizing the in vivo treatment parameters of
      the existing and new PDT candidates.

PMID- 21842895
TI  - Kinetic resolution of hindered Morita-Baylis-Hillman adducts by Rh(I)-catalyzed
      asymmetric 1,4-addition/beta-hydroxyelimination.
AB  - A kinetic resolution of hindered Morita-Baylis-Hillman adducts has been
      successfully achieved in excellent selectivities via Rh(I)-catalyzed asymmetric
      1,4-addition/beta-hydroxyelimination with the use of a chiral sulfinamide/olefin
      hybrid ligand. This study provides a novel and efficient access to both optically
      active hindered highly functionalized alkenes and Morita-Baylis-Hillman adducts.

PMID- 21842896
TI  - Isoreticular expansion of metal-organic frameworks with triangular and square
      building units and the lowest calculated density for porous crystals.
AB  - The concept and occurrence of isoreticular (same topology) series of metal
      organic frameworks (MOFs) is reviewed. We describe the preparation,
      characterization, and crystal structures of three new MOFs that are isoreticular
      expansions of known materials with the tbo (Cu(3)(4,4',4''-(benzene-1,3,5-triyl
      tris(benzene-4,1-diyl))tribenzoate)(2), MOF-399) and pto topologies
      (Cu(3)(4,4',4''-(benzene-1,3,5-triyl-tribenzoate)(2), MOF-143; Cu(3)(4,4',4''
      (triazine-2,4,6-triyl-tris(benzene-4,1-diyl))tribenzoate)(2), MOF-388). One of
      these materials (MOF-399) has a unit cell volume 17 times larger than that of the
      first reported material isoreticular to it, and has the highest porosity (94%)
      and lowest density (0.126 g cm(-3)) of any MOFs reported to date.

PMID- 21842897
TI  - Silylation of the uranyl ion using B(C6F5)3-activated Et3SiH.
AB  - Addition of 2 equiv of HSiEt(3) to UO(2)((Ar)acnac)(2) ((Ar)acnac =
      ArNC(Ph)CHC(Ph)O, Ar = 3,5-(t)Bu(2)C(6)H(3)) in the presence of 1 equiv of
      B(C(6)F(5))(3) results in formation of the U(V) bis(silyloxide) complex
      [U(OSiEt(3))(2)((Ar)acnac)(2)][HB(C(6)F(5))(3)] (1) in 80% yield. Also produced
      in the reaction, as a minor product, is
      U(OSiEt(3))(OB{C(6)F(5)}(3))((Ar)acnac)(2) (2). Interestingly, thermolysis of 1
      at 85  degrees C for 24 h also results in formation of 2, concomitant with
      production of Et(3)SiH. Addition of 1 equiv of Cp(2)Co to 1 results in formation
      of U(OSiEt(3))(2)((Ar)acnac)(2) (3) and [Cp(2)Co][HB(C(6)F(5))(3)] (4), which can
      be isolated in 61% and 71% yields, respectively. Complexes 1-3 have been
      characterized by X-ray crystallography, while the solution-phase redox properties
      of 1 have been measured with cyclic voltammetry.

PMID- 21842898
TI  - Bioaccumulation and effects of CdTe/CdS quantum dots on Chlamydomonas reinhardtii
      - nanoparticles or the free ions?
AB  - In order to properly assess the environmental risk of engineered nanoparticles
      (ENP), it is necessary to determine their fate (including dissolution,
      aggregation, and bioaccumulation) under representative environmental conditions.
      CdTe/CdS quantum dots (QD), such as those used in medical imaging, are known to
      release Cd(2+) due (mainly) to the dissolution of their outer shell. In this
      study, Chlamydomonas reinhardtii was exposed to either a soluble Cd salt or QD at
      similar concentrations of total Cd. Free Cd concentrations were measured using
      the Absence of Gradients and Nernstian Equilibrium Stripping technique. QD
      dissolution increased with decreasing pH and with increasing QD concentration.
      When exposed to QD, bioaccumulation was largely accounted for by dissolved Cd.
      Nonetheless, QD were shown to be taken up by the cells and to provoke unique
      biological effects. Whole transcriptome screening using RNA-Seq analysis showed
      that the free Cd and the QD had distinctly different biological effects.

PMID- 21842899
TI  - Influence of scaffold size on bactericidal activity of nitric oxide-releasing
      silica nanoparticles.
AB  - A reverse microemulsion synthesis was used to prepare amine-functionalized silica
      nanoparticles of three distinct sizes (i.e., 50, 100, and 200 nm) with similar
      amine content. The resulting hybrid nanoparticles, consisting of N-(6
      aminohexyl)aminopropyltrimethoxysilane and tetraethoxysilane, were highly
      monodisperse in size. N-Diazeniumdiolate nitric oxide (NO) donors were
      subsequently formed on secondary amines while controlling reaction conditions to
      keep the total amount of NO released constant for each particle size. The
      bactericidal efficacy of the NO-releasing nanoparticles against Pseudomonas
      aeruginosa increased with decreasing particle size. Additionally, smaller
      diameter nanoparticles were found to associate with the bacteria at a faster rate
      and to a greater extent than larger particles. Neither control (non-NO-releasing)
      nor NO-releasing particles exhibited toxicity toward L929 mouse fibroblasts at
      concentrations above their respective minimum bactericidal concentrations. This
      study represents the first investigation of the bactericidal efficacy of NO
      releasing silica nanoparticles as a function of particle size.

PMID- 21842900
TI  - Asymmetric catalysis of Diels-Alder reactions with in situ generated heterocyclic
      ortho-quinodimethanes.
AB  - The Diels-Alder reaction is probably the most powerful technology in the
      synthetic repertoire for single-step constructions of complex chiral molecules.
      The synthetic power of this fundamental pericyclic transformation has greatly
      increased with the emergence of asymmetric catalytic variants, and research aimed
      at further expanding its potential is still exciting and fascinating the chemical
      community. Here, we document the first asymmetric catalytic Diels-Alder reaction
      of in situ generated heterocyclic ortho-quinodimethanes (oQDMs), reactive diene
      species that have never before succumbed to a catalytic approach. Asymmetric
      aminocatalysis, that uses chiral amines as catalysts, is the enabling strategy to
      induce the transient generation of indole-, pyrrole- or furan-based oQDMs from
      simple starting materials, while directing the pericyclic reactions with
      nitroolefins and methyleneindolinones toward a highly stereoselective pathway.
      The approach provides straightforward access to polycyclic heteroaromatic
      compounds, which would be difficult to synthesize by other catalytic methods, and
      should open new synthetic pathways to complex chiral molecules using
      nontraditional disconnections.

PMID- 21842901
TI  - Using river distance and existing hydrography data can improve the geostatistical
      estimation of fish tissue mercury at unsampled locations.
AB  - Mercury in fish tissue is a major human health concern. Consumption of mercury
      contaminated fish poses risks to the general population, including potentially
      serious developmental defects and neurological damage in young children.
      Therefore, it is important to accurately identify areas that have the potential
      for high levels of bioaccumulated mercury. However, due to time and resource
      constraints, it is difficult to adequately assess fish tissue mercury on a basin
      wide scale. We hypothesized that, given the nature of fish movement along
      streams, an analytical approach that takes into account distance traveled along
      these streams would improve the estimation accuracy for fish tissue mercury in
      unsampled streams. Therefore, we used a river-based Bayesian Maximum Entropy
      framework (river-BME) for modern space/time geostatistics to estimate fish tissue
      mercury at unsampled locations in the Cape Fear and Lumber Basins in eastern
      North Carolina. We also compared the space/time geostatistical estimation using
      river-BME to the more traditional Euclidean-based BME approach, with and without
      the inclusion of a secondary variable. Results showed that this river-based
      approach reduced the estimation error of fish tissue mercury by more than 13% and
      that the median estimate of fish tissue mercury exceeded the EPA action level of
      0.3 ppm in more than 90% of river miles for the study domain.

PMID- 21842902
TI  - Molecular complexity via C-H activation: a dehydrogenative Diels-Alder reaction.
AB  - Traditionally, C-H oxidation reactions install oxidized functionality onto a
      preformed molecular skeleton, resulting in a local molecular change. The use of C
      H activation chemistry to construct complex molecular scaffolds is a new area
      with tremendous potential in synthesis. We report a Pd(II)/bis-sulfoxide
      catalyzed dehydrogenative Diels-Alder reaction that converts simple terminal
      olefins into complex cycloadducts in a single operation.

PMID- 21842903
TI  - Tandem Prins/Friedel-Crafts cyclization for stereoselective synthesis of
      heterotricyclic systems.
AB  - Homoallylic substrates such as (E)-6-arylhex-3-enyl alcohols, N-tosylamides, and
      thiols undergo smooth cross-coupling with various aldehydes in the presence of 10
      mol % Sc(OTf)(3) and 30 mol % TsOH to afford the trans-fused hexahydro-1H
      benzo[f]isochromenes, N-tosyloctahydrobenzo[f]isoquinolines, and hexahydro-1H
      benzo[f]isothiochromenes, respectively. However, the cross-coupling of (Z)
      olefins such as 6-arylhex-3-enyl alcohols, N-tosylamides, and thiols with
      aldehydes affords the corresponding hexahydro-1H-benzo[f]isochromenes, N
      tosyloctahydrobenzo[f]isoquinolines, and hexahydro-1H-benzo[f]isothiochromenes
      with complete cis selectivity via intramolecular Prins-, aza-Prins-, and thia
      Prins/Friedel-Crafts cyclizations, respectively. Though the Prins cyclization
      proceeds smoothly under the influence of Sc(OTf)(3), high conversions and
      enhanced reaction rates are achieved using a mixture of Sc(OTf)(3) and TsOH
      (1:3).

PMID- 21842904
TI  - Amplification, mutation, and sequencing of a six-letter synthetic genetic system.
AB  - The next goals in the development of a synthetic biology that uses artificial
      genetic systems will require chemistry-biology combinations that allow the
      amplification of DNA containing any number of sequential and nonsequential
      nonstandard nucleotides. This amplification must ensure that the nonstandard
      nucleotides are not unidirectionally lost during PCR amplification
      (unidirectional loss would cause the artificial system to revert to an all
      natural genetic system). Further, technology is needed to sequence artificial
      genetic DNA molecules. The work reported here meets all three of these goals for
      a six-letter artificially expanded genetic information system (AEGIS) that
      comprises four standard nucleotides (G, A, C, and T) and two additional
      nonstandard nucleotides (Z and P). We report polymerases and PCR conditions that
      amplify a wide range of GACTZP DNA sequences having multiple consecutive
      unnatural synthetic genetic components with low (0.2% per theoretical cycle)
      levels of mutation. We demonstrate that residual mutation processes both
      introduce and remove unnatural nucleotides, allowing the artificial genetic
      system to evolve as such, rather than revert to a wholly natural system. We then
      show that mechanisms for these residual mutation processes can be exploited in a
      strategy to sequence "six-letter" GACTZP DNA. These are all not yet reported for
      any other synthetic genetic system.

PMID- 21842905
TI  - Dynamic properties of microemulsions in the single-phase channels.
AB  - We have studied the dynamic and rheological properties in the single-phase
      channels of a microemulsion system with a mixed anionic/nonionic surfactant
      system and decane from the aqueous to the oil phase. One isotropic channel,
      called the "upper" channel, begins at the L(3) phase (sponge-like phase) of the
      binary surfactant mixture on the water side and passes with a shallow minimum for
      the surfactant composition to the oil side. The other "lower" single-phase
      channel begins at the micellar L(1) phase and ends in the middle of the phase
      diagram. Both isotropic channels are separated by a huge anisotropic single phase
      L(alpha) channel that reaches from the water side to 90% of oil in the solvent
      mixture. The structural relaxation time of the viscous fluids could be measured
      with electric birefringence (EB) measurements, where a signal is caused by the
      deformation of the internal nanostructure of the fluids by an electric field. For
      the L(3) phase, the EB signal can be fitted with a single time constant. With
      increasing oil in the upper channel, the main structural relaxation time passes
      over a maximum and correlates with the viscosity. Obviously, this time constant
      controls the viscosity of the fluid (eta(o) = G'.tau). It is remarkable that the
      longest structural relaxation time increases three decades, and the viscosity
      increases two decades when 10% of oil is solubilized into the L(3) phase.
      Conductivity data imply that the fluid in the upper channel has a bicontinuous
      structure from the L(3) phase to the microemulsion with only 10% oil. In this oil
      range, the conductivity decreases three decades, and the electric birefringence
      signals are complicated because of a superposition of up to three processes. For
      higher oil ratios, the structure obviously changes to a HIPE (high internal phase
      emulsion) structure with water droplets in the oil matrix.

PMID- 21842906
TI  - Experimental and computational study of the formation mechanism of the
      diammoniate of diborane: the role of dihydrogen bonds.
AB  - The mechanism of formation of ammonia borane (NH(3)BH(3), AB) and the diammoniate
      of diborane ([H(2)B(NH(3))(2)][BH(4)], DADB) in the reaction between NH(3) and
      THF.BH(3) was explored experimentally and computationally. Ammonia diborane
      (NH(3)BH(2)(MU-H)BH(3), AaDB), a long-sought intermediate proposed for the
      formation of DADB, was directly observed in the reaction using (11)B NMR
      spectroscopy. The results indicate that dihydrogen bonds between the initially
      formed AB and AaDB accelerate the formation of DADB in competition with the
      formation of AB.

PMID- 21842907
TI  - Physicochemical properties of soy protein: effects of subunit composition.
AB  - Soy protein elastomer (SPE) exhibits elastic, extensible, and sticky properties
      in its native state and displays great potential as an alternative to wheat
      gluten. The objective of this study was to better understand the roles of soy
      protein subunits (polypeptides) contributing to the functional properties of SPE.
      Six soy protein samples with different subunit compositions were prepared by
      extracting the proteins at various pH values on the basis of the different
      solubilities of conglycinin (7S) and glycinin (11S) globulins. Soy protein
      containing a large amount of high molecular weight aggregates formed from alpha'
      and alpha subunits exhibited stronger viscoelastic solid behavior than other soy
      protein samples in terms of dynamic elastic and viscous modules. Electrophoresis
      results revealed that these aggregates are mainly stabilized through disulfide
      bonds, which also contributed to higher denaturation enthalpy as characterized by
      DSC and larger size protein aggregates observed by TEM. Besides, the most
      viscoelastic soy protein sample exhibited flat and smooth surfaces of the protein
      particles as observed by SEM, whereas other samples had rough and porous particle
      surfaces. It was proposed that the ability of alpha' and alpha to form aggregates
      and the resultant proper protein-protein interaction in soy proteins are the
      critical contributions to the continuous network of SPE.

PMID- 21842908
TI  - Comparative study of the interaction of O2 and C2H4 with small vanadium clusters
      from density functional theory.
AB  - We have studied C(2)H(4) and O(2) molecules separately or simultaneously for
      adsorption on V(n) (n = 2-8) clusters, and V(n) clusters catalyzed ethylene
      oxidation to acetaldehyde using spin-polarized density functional theory
      calculations. Molecular adsorption and clear size-dependent adsorption energy are
      predicted for C(2)H(4). O(2) is dissociately adsorbed with nearly constant
      adsorption energy. In the case of coadsorption, O(2) and C(2)H(4) adsorb on the
      V(n) surface simultaneously. Each keeps the same adsorption form, molecular or
      dissociative, as in separate adsorption. The noted cooperative effect is noted in
      C(2)H(4) and O(2) coadsorption, which activates the C-C double bond of C(2)H(4)
      and favors its oxidization. Furthermore, both the separate and coadsorptions
      result in magnetic enhancement or reduction of V(n), which is found to be
      dependent on the cluster size and the adsorbates. In addition, we reveal the
      reaction mechanism of V(2) (V(6))-catalyzed ethylene oxidation to acetaldehyde
      and find the overall reaction is exothermic and barrierless.

PMID- 21842909
TI  - A photochemical on-off switch for tuning the equilibrium mixture of H2 nuclear
      spin isomers as a function of temperature.
AB  - The photochemical interconversion of the two allotropes of the hydrogen molecule
      [para-H(2) (pH(2)) and ortho-H(2) (oH(2))] incarcerated inside the fullerene
      C(70) (pH(2)@C(70) and oH(2)@C(70), respectively) is reported. Photoexcitation of
      H(2)@C(70) generates a fullerene triplet state that serves as a spin catalyst for
      pH(2)/oH(2) conversion. This method provides a means of changing the pH(2)/oH(2)
      ratio inside C(70) by simply irradiating H(2)@C(70) at different temperatures,
      since the equilibrium ratio is temperature-dependent and the electronic triplet
      state of the fullerene produced by absorption of the photon serves as an "on-off"
      spin catalyst. However, under comparable conditions, no photolytic pH(2)/oH(2)
      interconversion was observed for H(2)@C(60), which was rationalized by the
      significantly shorter triplet lifetime of H(2)@C(60) relative to H(2)@C(70).

PMID- 21842910
TI  - Hydrogen bonding behaviors of binary systems containing the ionic liquid 1-butyl
      3-methylimidazolium trifluoroacetate and water/methanol.
AB  - The hydrogen-bonding properties of binary systems consisting of a representative
      Bronsted acidic hydrophilic ionic liquid (IL) 1-butyl-3-methylimidazolium
      trifluoroacetate ([Bmim][CF(3)CO(2)]) and a cosolvent, water or methanol, over
      the entire concentration range have been investigated by methods of attenuated
      total reflectance infrared spectroscopy, (1)H NMR spectroscopy, and quantum
      chemical calculations. It has been found that the hydrogen-bonding interactions
      between the anion [CF(3)CO(2)](-), rather than the cation, and the cosolvent
      molecules are dominant at low concentration of cosolvent. The H-bond interaction
      site between the IL anion and water/methanol is the O atom in the -COO group,
      while the -CF(3) group makes a positive contribution by donating electron to the
      carboxylic group, forming a cooperative hydrogen-bonding system. For the cation
      [Bmim](+), although the C2-H is the favorable proton donor in H-bonding
      interactions, the water/methanol molecules form H-bonds with the alkyl C-H at low
      water/methanol concentration due to the stronger interaction between C2-H and
      [CF(3)CO(2)](-). Interestingly, we found that the interaction between methanol
      and the IL is stronger than that between water and the IL because the methyl
      group in methanol has a positive contribution to the formation of H-bonds. The
      following sequential order of interaction strength is established: [Bmim](+)
      methanol-[CF(3)CO(2)](-) > [Bmim](+)-water-[CF(3)CO(2)](-) > [Bmim](+)
      [CF(3)CO(2)](-) > [CF(3)CO(2)](-)-methanol > [CF(3)CO(2)] (-)-water > [Bmim](+)
      methanol > [Bmim] (+)-water.

PMID- 21842911
TI  - Evaluation of different multidimensional LC-MS/MS pipelines for isobaric tags for
      relative and absolute quantitation (iTRAQ)-based proteomic analysis of potato
      tubers in response to cold storage.
AB  - Cold-induced sweetening in potato tubers is a costly problem for the food
      industry. To systematically identify the proteins associated with this process,
      we employed a comparative proteomics approach using isobaric, stable isotope
      coded labels to compare the proteomes of potato tubers after 0 and 5 months of
      storage at 5  degrees C. We evaluated both high pH reverse phase (hpRP) liquid
      chromatography (LC) and off-gel electrophoresis (OGE) as first dimension
      fractionation methods followed by nanoLC-MS/MS, using two high performance mass
      spectrometry platforms (Q-TOF and Orbitrap). We found that hpRP-LC consistently
      offered better resolution, reduced expression ratio compression, and a more MS
      compatible workflow than OGE and consistently yielded more unique peptide/protein
      identifications and higher sequence coverage with better quantification. In this
      study, a total of 4463 potato proteins were identified, of which 46 showed
      differential expressions during potato tuber cold storage. Several key proteins
      important in controlling starch-sugar conversion, which leads to cold-induced
      sweetening, as well as other proteins that are potentially involved in this
      process, were identified. Our results suggest that the hpRP-RP shotgun approach
      is a feasible and practical workflow for discovering potential protein candidates
      in plant proteomic analysis.

PMID- 21842912
TI  - Size of free neutral CO2 clusters from carbon 1s ionization energies.
AB  - Free neutral CO(2) clusters were produced by adiabatic expansion and
      characterized by carbon 1s (C1s) photoelectron spectroscopy using synchrotron
      radiation. The shift in C1s ionization energy (IE) between the cluster and the
      monomer, i.e., DeltaIE = IE(cluster) - IE(monomer), was found to vary
      systematically with the experimental conditions. A functional relationship is
      established between the mean cluster size in the beam, <N>, and DeltaIE, in good
      agreement with theoretical calculations of shifts in ionization energy for model
      clusters. This makes it possible to use core-level photoelectron spectroscopy to
      monitor the mean cluster size and also to estimate <N> from expansion conditions.

PMID- 21842913
TI  - Visualization and analysis of the complexome network of Saccharomyces cerevisiae.
AB  - Most processes in the cell are delivered by protein complexes, rather than
      individual proteins. While the association of proteins has been studied
      extensively in protein-protein interaction networks (the interactome), an
      intuitive and effective representation of complex-complex connections (the
      complexome) is not yet available. Here, we describe a new representation of the
      complexome of Saccharomyces cerevisiae. Using the core-module-attachment data of
      Gavin et al. (  Nature     2006  ,   440  ,   631 - 6  ), protein complexes in
      the network are represented as nodes; these are connected by edges that represent
      shared core and/or module protein subunits. To validate this network, we examined
      the network topology and its distribution of biological processes. The complexome
      network showed scale-free characteristics, with a power law-like node degree
      distribution and clustering coefficient independent of node degree. Connected
      complexes in the network showed similarities in biological process that were
      nonrandom. Furthermore, clusters of interacting complexes reflected a higher
      level organization of many cellular functions. The strong functional
      relationships seen in these clusters, along with literature evidence, allowed 44
      uncharacterized complexes to be assigned putative functions using guilt-by
      association. We demonstrate our network model using the GEOMI visualization
      platform, on which we have developed capabilities to integrate and visualize
      complexome data.

PMID- 21842915
TI  - Relativistic-consistent electron densities of the coinage metal clusters M2, M4,
      M4(2-), and M4Na2 (M = Cu, Ag, Au): a QTAIM study.
AB  - We employ second-order Moller-Plesset perturbation theory level in combination
      with recently developed pseudopotential-based correlation consistent basis sets
      to obtain accurate relativistic-consistent electron densities for small coinage
      metal clusters. Using calculated electron densities, we employ Bader's quantum
      theory of atoms in molecules (QTAIM) to gain insights into the nature of metal
      metal bonding in the clusters M(2), M(4), M(4)(2-), and M(4)Na(2) (M = Cu, Ag,
      Au). For the simplest case of the metal dimer, M(2), we correlate the strength of
      the metal-metal bond with the value of the electron density at the bond critical
      point, the total energy density at the bond critical point, the sharing
      (delocalization) index, and the values of the two principle negative curvatures.
      We then consider changes to the metal-metal bonding and charge density
      distribution upon the addition of two metal atoms to form the metal tetramer,
      M(4), and then followed by the addition of an electron pair to form M(4)(2-) and
      finally followed by the addition of two alkali metal (sodium) ions to form
      M(4)Na(2). Using topological properties of the electron density, we present
      evidence for the existence of sigma-aromaticity in Au(4)(2-). We also report the
      existence of two non-nuclear attractors in the molecular graph of Cu(4)(2-) and
      large negative charge accumulation in the nonbonded Cu basins of this cluster.

PMID- 21842916
TI  - Palladium induced macrocyclic preorganization for stabilization of a
      tetrathiafulvalene mixed-valence dimer.
AB  - Ditopic metalation of a flexible "Pacman"-like tetrathiafulvalene (TTF) modified
      Schiff-base-calixpyrrole results in the stabilization upon oxidation of an
      otherwise difficult-to-access mixed-valence TTF radical dimer. EPR and optical
      spectroscopies were used to characterize the mixed-valence species.

PMID- 21842917
TI  - Communication: Conformation state diagram of polypeptides: a chain length induced
      alpha-beta transition.
AB  - By using a generic coarse grained polypeptide model, we perform multicanonical
      molecular dynamics simulations for determining the equilibrium conformation state
      diagram of a single homopolypeptide chain as a function of the chain length and
      temperature. The state diagram highlights the thermal regimes of stability for
      various conformational patterns in polypeptides, including swollen, random and
      collapsed coils, globular structures, extended and bended alpha helices, and
      compact beta bundles. Remarkably, at low temperatures we observe a sharp
      transition from extended alpha helix to compact beta bundles as the chain length
      increases. This finding indicates that the chain length is one of the intrisic
      factors that can trigger alpha-beta transformations in a broad class of
      polypeptides.

PMID- 21842918
TI  - Communication: Where does the first water molecule go in imidazole?
AB  - Supersonic jet FTIR spectroscopy supplemented by (18)O substitution shows
      unambiguously that water prefers to act as an O-H...N hydrogen bond donor towards
      imidazole, instead of acting as a N-H...O acceptor. Previous matrix isolation,
      helium droplet, and aromatic substitution experiments had remained ambiguous, as
      are standard quantum chemical calculations. The finding is supported by a study
      of the analogous methanol complexes and by higher level quantum chemical
      calculations.

PMID- 21842919
TI  - Communication: Iteration-free, weighted histogram analysis method in terms of
      intensive variables.
AB  - We present an iteration-free weighted histogram method in terms of intensive
      variables that directly determines the inverse statistical temperature, beta(S) =
      ?S/?E, with S the microcanonical entropy. The method eliminates iterative
      evaluations of the partition functions intrinsic to the conventional approach and
      leads to a dramatic acceleration of the posterior analysis of combining
      statistically independent simulations with no loss in accuracy. The synergistic
      combination of the method with generalized ensemble weights provides insights
      into the nature of the underlying phase transitions via signatures in beta(S)
      characteristic of finite size systems. The versatility and accuracy of the method
      is illustrated for the Ising and Potts models.

PMID- 21842920
TI  - Using a pruned basis, a non-product quadrature grid, and the exact Watson normal
      coordinate kinetic energy operator to solve the vibrational Schrodinger equation
      for C2H4.
AB  - In this paper we propose and test a method for computing numerically exact
      vibrational energy levels of a molecule with six atoms. We use a pruned product
      basis, a non-product quadrature, the Lanczos algorithm, and the exact normal
      coordinate kinetic energy operator (KEO) with the pi(t)MUpi term. The Lanczos
      algorithm is applied to a Hamiltonian with a KEO for which MU is evaluated at
      equilibrium. Eigenvalues and eigenvectors obtained from this calculation are used
      as a basis to obtain the final energy levels. The quadrature scheme is designed,
      so that integrals for the most important terms in the potential will be exact.
      The procedure is tested on C(2)H(4). All 12 coordinates are treated explicitly.
      We need only ~1.52 * 10(8) quadrature points. A product Gauss grid with which one
      could calculate the same energy levels has at least 5.67 * 10(13) points.

PMID- 21842921
TI  - Effective Hamiltonian of liquid-vapor curved interfaces in mean field.
AB  - We analyze a one-component simple fluid in a liquid-vapor coexistence state,
      which forms an arbitrarily curved interface. By using an approach based on
      density functional theory, we obtain an exact and simple expression for the grand
      potential at the level of mean field approximation that depends on the density
      profile and the short-range interaction potential. By introducing the step
      function approximation for the density profile, and using general geometric
      arguments, we expand the grand potential in powers of the principal curvatures of
      the surface and find consistency with the Helfrich phenomenological model in the
      second order approximation.

PMID- 21842922
TI  - The relationship between double excitation amplitudes and Z vector components in
      some post-Hartree-Fock correlation methods.
AB  - The relationship between Z vector components and excitation amplitudes is
      analyzed for several post-Hartree-Fock correlation methods limited to double
      excitation amplitudes. An analytical formula approximating the Z vector for the
      coupled cluster doubles method is presented and shown to be quite accurate. This
      approximation is also used to determine the prefactor of the norm of doubly
      excited states in averaged coupled pair functional-type energy functionals self
      consistently leading to better agreement with coupled cluster results.

PMID- 21842923
TI  - Improving the convergence of closed and open path integral molecular dynamics via
      higher order Trotter factorization schemes.
AB  - Higher order factorization schemes are developed for path integral molecular
      dynamics in order to improve the convergence of estimators for physical
      observables as a function of the Trotter number. The methods are based on the
      Takahashi-Imada and Susuki decompositions of the Boltzmann operator. The methods
      introduced improve the averages of the estimators by using the classical forces
      needed to carry out the dynamics to construct a posteriori weighting factors for
      standard path integral molecular dynamics. The new approaches are straightforward
      to implement in existing path integral codes and carry no significant overhead.
      The Suzuki higher order factorization was also used to improve the end-to-end
      distance estimator in open path integral molecular dynamics. The new schemes are
      tested in various model systems, including an ab initio path integral molecular
      dynamics calculation on the hydrogen molecule and a quantum water model. The
      proposed algorithms have potential utility for reducing the cost of path integral
      molecular dynamics calculations of bulk systems.

PMID- 21842924
TI  - A method for treating the passage of a charged hard sphere ion as it passes
      through a sharp dielectric boundary.
AB  - In the implicit solvent models of electrolytes (such as the primitive model
      (PM)), the ions are modeled as point charges in the centers of spheres (hard
      spheres in the case of the PM). The surfaces of the spheres are not polarizable
      which makes these models appropriate to use in computer simulations of
      electrolyte systems where these ions do not leave their host dielectrics. The
      same assumption makes them inappropriate in simulations where these ions cross
      dielectric boundaries because the interaction energy of the point charge with the
      polarization charge induced on the dielectric boundary diverges. In this paper,
      we propose a procedure to treat the passage of such ions through dielectric
      interfaces with an interpolation method. Inspired by the "bubble ion" model (in
      which the ion's surface is polarizable), we define a space-dependent effective
      dielectric coefficient, epsilon(eff)(r), for the ion that overlaps with the
      dielectric boundary. Then, we replace the "bubble ion" with a point charge that
      has an effective charge q/epsilon(eff)(r) and remove the portion of the
      dielectric boundary where the ion overlaps with it. We implement the
      interpolation procedure using the induced charge computation method [D. Boda, D.
      Gillespie, W. Nonner, D. Henderson, and B. Eisenberg, Phys. Rev. E 69, 046702
      (2004)]. We analyze the various energy terms using a spherical ion passing
      through an infinite flat dielectric boundary as an example.

PMID- 21842925
TI  - A practical integral equation for the structure and thermodynamics of hard sphere
      Coulomb fluids.
AB  - A closure for the Ornstein-Zernike equation is presented, applicable for fluids
      of charged, hard spheres. From an exact, but intractable closure, we derive the
      radial distribution function of nonlinearized Debye-Huckel theory by subsequent
      approximations, and use the information to formulate a new closure by an
      extension of the mean spherical approximation. The radial distribution functions
      of the new closure, coined Debye-Huckel-extended mean spherical approximation,
      are in excellent agreement with those resulting from the hyper-netted chain
      approximation and molecular dynamics simulations, in the regime where the latter
      are applicable, except for moderately dilute systems at low temperatures where
      the structure agrees at most qualitatively. The method is numerically more
      efficient, and more important, convergent in the entire temperature-density
      plane. We demonstrate that the method is accurate under many conditions for the
      determination of the structural and thermodynamic properties of homogeneous,
      symmetric hard-sphere Coulomb systems, and estimate it to be a valuable basis for
      the formulation of density functional theories for inhomogeneous or highly
      asymmetric systems.

PMID- 21842926
TI  - High purity chemical etching and thermal passivation process for Ge(001) as
      nanostructure template.
AB  - An advanced two-step cleaning process of the Ge(001) surface for nanoscience
      requirements is presented. First, wet-chemical etching with a variant of the
      Piranha solution (H(2)SO(4), H(2)O(2), H(2)O) is used to remove contaminants as
      well as the native oxide layer. Second, passivation of the surface is achieved by
      a rapid thermal oxidation step, leading to a homogeneous protective oxide layer.
      The thickness of the oxide layer is tuned to be thick enough to protect the
      surface, yet thin enough to be completely removed by thermal treatment in ultra
      high vacuum. The application of this recipe results in an outstandingly clean and
      atomically flat surface, with carbon contamination at the detection limit of x
      ray photoelectron spectroscopy. Scanning tunneling microscopy and electron
      diffraction reveal a long range ordered surface with typical terrace diameters of
      ~100 nm, suitable for the growth of atomic-scale nanostructures.

PMID- 21842927
TI  - Dynamical regimes on the Cl + H2 collisions: inelastic rainbow scattering.
AB  - While Cl + H(2) reactive collisions have been a subject of numerous experimental
      and theoretical studies, inelastic collisions leading to rotational energy
      transfer and/or vibrational excitation have been largely ignored. In this work,
      extensive quantum mechanical calculations covering the 0.5-1.5 eV total energy
      range and various initial rovibrational states have been carried out and used to
      perform a joint study of inelastic and reactive Cl + H(2) collisions.
      Quasiclassical trajectories calculations complement the quantum mechanical
      results. The analysis of the inelastic transition probabilities has revealed the
      existence of two distinct dynamical regimes that correlate with low and high
      impact parameters, b, and are neatly separated by glory scattering. It has been
      found that while high-b collisions are mainly responsible for |Deltaj| = 2
      transitions which dominate the inelastic scattering, they are very inefficient in
      promoting higher |Deltaj| transitions. The effectiveness of this type of
      collision also drops with rotational excitation of H(2). In contrast, reactive
      scattering, that competes with |Deltaj| > 2 inelastic transitions, is exclusively
      caused by low-b collisions, and it is greatly favored when the reactants get
      rotationally excited. Previous studies focusing on the reactivity of the Cl +
      H(2) system established that the van der Waals well located in the entrance
      channel play a key role in determining the mechanism of the collisions. Our
      results prove this to be also a case for inelastic processes, where the origin of
      the double dynamical regime can be traced back to the influence exerted by this
      well that shapes the topology of the entrance channel of the Cl-H(2) system.

PMID- 21842928
TI  - Polycyclic aromatic hydrocarbon-isomer fragmentation pathways: case study for
      pyrene and fluoranthene molecules and clusters.
AB  - We report on measurements of the ionization and fragmentation of polycyclic
      aromatic hydrocarbon (PAH) targets in Xe(20+) + C(16)H(10) and Xe(20+) +
      [C(16)H(10)](k) collisions and compare results for the two C(16)H(10) isomers:
      pyrene and fluoranthene. For both types of targets, i.e., for single PAH
      molecules isolated in vacuum or for isomerically pure clusters of one of the
      molecules, the resulting fragment spectra are surprisingly similar. However, we
      do observe weak but significant isomer effects. Although these are manifested in
      very different ways for the monomer and cluster targets, they both have at their
      roots small differences (<2.5 eV) between the total binding energies of neutral,
      and singly and multiply charged pyrene and fluoranthene monomers. The results
      will be discussed in view of the density functional theory calculations of
      ionization and dissociation energies for fluoranthene and pyrene. A simple
      classical over-the-barrier model is used to estimate cross sections for single-
      and multiple-electron transfer between PAHs and ions. Calculated single and
      multiple ionization energies, and the corresponding model PAH ionization cross
      sections, are given.

PMID- 21842929
TI  - Dissociative double ionization of 1-bromo-2-chloroethane irradiated by an intense
      femtosecond laser field.
AB  - The dissociative double ionization and multi-photon ionization of 1-bromo-2
      chloroethane (BCE) irradiated by the 800 nm femtosecond laser field have been
      investigated by dc-slice imaging technology. The charged parent ion ratio
      [BCE(2+)]/[BCE(+)] was measured, and the corresponding ionization process
      including non-sequential double ionization and sequential double ionization was
      analyzed. The sliced images of different photo-dissociated ions were detected,
      and the corresponding kinetic energy release (KER) distributions were calculated
      and extracted. Furthermore, the dissociative double ionization channels,
      attributed to the cleavage of the C-C, C-Br, and C-Cl bonds by the Coulombic
      repulsive forces, were discussed, and the revised equilibrium distance R(e)*, the
      energy ratio E(exp)/E(coul), and the value a=?(R(e)*)/(E(exp)/E(coul)) were
      calculated.

PMID- 21842930
TI  - Quantifying cooperative intermolecular interactions for improved carbon dioxide
      capture materials.
AB  - We have optimized the geometry and calculated interaction energies for over 100
      different complexes of CO(2) with various combinations of electron accepting
      (Lewis acid) and electron donating (Lewis base) molecules. We have used the
      recently developed explicitly correlated coupled cluster singles doubles and
      perturbative triples [CCSD(T)-F12] methods and the associated VXZ-F12 (where X =
      D,T,Q) basis sets. We observe only modest changes in the geometric parameters of
      CO(2) upon complexation, which suggests that the geometry of CO(2) adsorbed in a
      nanoporous material should be similar to that of CO(2) in gas phase. When CO(2)
      forms a complex with two Lewis acids via the two electron rich terminal oxygen
      atoms, the interaction energy is less than twice what would be expected for the
      same complex involving a single Lewis acid. We consider a series of complexes
      that exhibit simultaneous CO(2)-Lewis acid and CO(2)-Lewis base intermolecular
      interactions, with total interaction energies spanning 14.1-105.9 kJ mol(-1). For
      these cooperative complexes, we find that the total interaction energy is greater
      than the sum of the interaction energies of the constituent complexes.
      Furthermore, the intermolecular distances of the cooperative complexes are
      contracted as compared to the constituent complexes. We suggest that metal
      organic-framework or similar nanoporous materials could be designed with
      adsorption sites specifically tailored for CO(2) to allow cooperative
      intermolecular interactions, facilitating enhanced CO(2) adsorption.

PMID- 21842931
TI  - Structure of the alkali-metal-atom + strontium molecular ions: towards
      photoassociation and formation of cold molecular ions.
AB  - The potential energy curves, permanent and transition dipole moments, and the
      static dipolar polarizability, of molecular ions composed of one alkali-metal
      atom and a strontium ion are determined with a quantum chemistry approach. The
      molecular ions are treated as effective two-electron systems and are treated
      using effective core potentials including core polarization, large gaussian basis
      sets, and full configuration interaction. In the perspective of upcoming
      experiments aiming at merging cold atom and cold ion traps, possible paths for
      radiative charge exchange, photoassociation of a cold lithium or rubidium atom
      and a strontium ion are discussed, as well as the formation of stable molecular
      ions.

PMID- 21842932
TI  - Theoretical investigation of rotationally inelastic collisions of the methyl
      radical with helium.
AB  - Rotationally inelastic collisions of the CH(3) molecule in its ground X(2)A(2)''
      electronic state have been investigated. We have determined a potential energy
      surface (PES) for the interaction of rigid CH(3), frozen at its equilibrium
      geometry, with a helium atom, using a coupled-cluster method that includes all
      single and double excitations, as well as perturbative contributions of connected
      triple excitations [RCCSD(T)]. The anisotropy of the PES is dominated by
      repulsion of the helium by the hydrogen atoms. The dissociation energy D(e) was
      computed to equal 27.0 cm(-1). At the global minimum, the helium atom lies in the
      CH(3) plane between two C-H bonds at an atom-molecule separation R = 6.52 bohr.
      Cross sections for collision-induced rotational transitions have been determined
      through quantum scattering calculations for both nuclear spin modifications.
      Rotationally inelastic collisions can cause a change in the rotational angular
      momentum n and its body-frame projection k. Because of the anisotropy of the PES
      due to the hydrogen atoms, there is a strong propensity for Deltak = +/-3
      transitions. Thermal rate constants for state-specific total collisional removal
      have also been determined.

PMID- 21842933
TI  - The study for the incipient solvation process of NaCl in water: the observation
      of the NaCl-(H2O)n (n = 1, 2, and 3) complexes using Fourier-transform microwave
      spectroscopy.
AB  - Pure rotational spectra of the sodium chloride-water complexes, NaCl-(H(2)O)(n)
      (n = 1, 2, and 3), in the vibronic ground state have been observed by a Fourier-
      transform microwave spectrometer coupled with a laser ablation source. The (37)Cl
      isotopic species and a few deuterated species have also been observed. From the
      analyses of the spectra, the rotational constants, the centrifugal distortion
      constants, and the nuclear quadrupole coupling constants of the Na and Cl nuclei
      were determined precisely for all the species. The molecular structures of NaCl
      (H(2)O)(n) were determined using the rotational constants and the molecular
      symmetry. The charge distributions around Na and Cl nuclei in NaCl are
      dramatically changed by the complex formation with H(2)O. Prominent dependences
      of the bond lengths r(Na-Cl) on the number of H(2)O were also observed. By a
      comparison with results of theoretical studies, it is shown that the structure of
      NaCl-(H(2)O)(3) is approaching to that of the contact ion-pair, which is
      considered to be an intermediate species in the incipient solvation process.

PMID- 21842934
TI  - The air-broadened, near-infrared CO2 line shape in the spectrally isolated
      regime: evidence of simultaneous Dicke narrowing and speed dependence.
AB  - Frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) was employed to
      measure air-broadened CO(2) line shape parameters for transitions near 1.6 MUm
      over a pressure range of 6.7-33 kPa. The high sensitivity of FS-CRDS allowed for
      the first measurements in this wavelength range of air-broadened line shape
      parameters on samples with CO(2) mixing ratios near those of the atmosphere. The
      measured air-broadening parameters show several percent deviations (0.9%-2.7%)
      from values found in the HITRAN 2008 database. Spectra were fit with a variety of
      models including the Voigt, Galatry, Nelkin-Ghatak, and speed-dependent Nelkin
      Ghatak line profiles. Clear evidence of line narrowing was observed, which if
      unaccounted for can lead to several percent biases. Furthermore, it was observed
      that only the speed-dependent Nelkin-Ghatak line profile was able to model the
      spectra to within the instrumental noise level because of the concurrent effects
      of collisional narrowing and speed dependence of collisional broadening and
      shifting.

PMID- 21842935
TI  - The identification of a solvated electron pair in the gaseous clusters of Na(
      )(H2O)n and Li(-)(H2O)n.
AB  - By first principles calculations, we explore the possibility that Na(-)(H(2)O)(n)
      and Li(-)(H(2)O)(n) clusters, which have been measured previously by
      photoelectron experiments, could serve as gas-phase molecular models for the
      solvation of two electrons. Such models would capture the electron-electron
      interaction in a solution environment, which is missed in the well-known anionic
      water clusters (H(2)O)(n) (-). Our results show that by n = 10, the two loosely
      bound s electrons in Li(-)(H(2)O)(n) are indeed detached from lithium, and they
      could exist in either the singlet (spin-paring) or the triplet (spin-coupling)
      state. In contrast, the two electrons would prefer to stay on the sodium atom in
      Na(-)(H(2)O)(n) and on the surface of the cluster. The formation of a solvated
      electron pair and the variation in solvation structures make these two cluster
      series interesting subjects for further experimental investigation.

PMID- 21842936
TI  - Rotational spectrum of asymmetric top molecules in combined static and laser
      fields.
AB  - We examine the impact of the combination of a static electric field and a non
      resonant linearly polarized laser field on an asymmetric top molecule. Within the
      rigid rotor approximation, we analyze the symmetries of the Hamiltonian for all
      possible field configurations. For each irreducible representation, the
      Schrodinger equation is solved by a basis set expansion in terms of a linear
      combination of symmetric top eigenfunctions respecting the corresponding
      symmetries, which allows us to distinguish avoided crossings from genuine ones.
      Using the fluorobenzene and pyridazine molecules as prototypes, the rotational
      spectra and properties are analyzed for experimentally accessible static field
      strengths and laser intensities. Results for energy shifts, orientation,
      alignment, and hybridization of the angular motion are presented as the field
      parameters are varied. We demonstrate that a proper selection of the fields gives
      rise to a constrained rotational motion in three Euler angles, the wave function
      being oriented along the electrostatic field direction, and aligned in other two
      angles.

PMID- 21842937
TI  - Quantum molecular dynamic simulations of warm dense carbon monoxide.
AB  - Using quantum molecular dynamic simulations, we have studied the thermophysical
      properties of warm dense carbon monoxide under extreme conditions. The principal
      Hugoniot pressure up to 286 GPa, which is derived from the equation of state, is
      calculated and compared with available experimental and theoretical data. The
      chemical decomposition of carbon monoxide has been predicted at 8 GPa by means of
      pair correlation function and the charge density distribution. Based on Kubo
      Greenwood formula, the dc electrical conductivity and the optical reflectivity
      are determined, and the nonmetal-metal transition for shock compressed carbon
      monoxide is observed around 40 GPa.

PMID- 21842938
TI  - Modeling the first stages of Cu precipitation in alpha-Fe using a hybrid
      atomistic kinetic Monte Carlo approach.
AB  - We simulate the coherent stage of Cu precipitation in alpha-Fe with an atomistic
      kinetic Monte Carlo (AKMC) model. The vacancy migration energy as a function of
      the local chemical environment is provided on-the-fly by a neural network,
      trained with high precision on values calculated with the nudged elastic band
      method, using a suitable interatomic potential. To speed up the simulation,
      however, we modify the standard AKMC algorithm by treating large Cu clusters as
      objects, similarly to object kinetic Monte Carlo approaches. Seamless matching
      between the fully atomistic and the coarse-grained approach is achieved again by
      using a neural network, that provides all stability and mobility parameters for
      large Cu clusters, after training on atomistically informed results. The
      resulting hybrid algorithm allows long thermal annealing experiments to be
      simulated, within a reasonable CPU time. The results obtained are in very good
      agreement with several series of experimental data available from the literature,
      spanning over different conditions of temperature and alloy composition. We
      deduce from these results and relevant parametric studies that the mobility of Cu
      clusters containing one vacancy plays a central role in the precipitation
      mechanism.

PMID- 21842939
TI  - Molecular dynamics studies to understand the mechanism of heat accommodation in
      homogeneous condensing flow of carbon dioxide.
AB  - Using molecular dynamics (MD), we have studied the mechanism of heat
      accommodation between carbon dioxide clusters and monomers for temperatures and
      cluster size conditions that exist in homogeneous condensing supersonic expansion
      plumes. The work was motivated by our meso-scale direct simulation Monte Carlo
      and Bhatnagar-Gross-Krook based condensation simulations where we found that the
      heat accommodation model plays a key role in the near-field of the nozzle
      expansion particularly as the degree of condensation increases [R. Kumar, Z. Li,
      and D. Levin, Phys. Fluids 23, 052001 (2011)]. The heat released by nucleation
      and condensation and the heat removed by cluster evaporation can be transferred
      or removed from either the kinetic or translational modes of the carbon dioxide
      monomers. The molecular dynamics results show that the time required for gas
      cluster interactions to establish an equilibrium from an initial state of non
      equilibrium is less than the time step used in meso-scale analyses [R. Kumar, Z.
      Li, and D. Levin, Phys. Fluids 23, 052001 (2011)]. Therefore, the good agreement
      obtained between the measured cluster and gas number density and gas temperature
      profiles with the meso-scale modeling using the second energy exchange mechanism
      is not fortuitous but is physically based. Our MD simulations also showed that a
      dynamic equilibrium is established by the gas-cluster interactions in which
      condensation and evaporation processes take place constantly to and from a
      cluster.

PMID- 21842940
TI  - Accurate quantum-mechanical rate constants for a linear response Azzouz-Borgis
      proton transfer model employing the multilayer multiconfiguration time-dependent
      Hartree approach.
AB  - The multilayer multiconfiguration time-dependent Hartree (ML-MCTDH) method is
      applied to simulate the quantum dynamics and thermal rate constant of the Azzouz
      Borgis model of proton transfer in a polar solvent. To this end, the original
      atomistic potential is mapped to a system-bath model. Employing the flux
      correlation function formalism and importance sampling techniques, accurate
      quantum mechanical rate constants are obtained, which provide a benchmark for
      evaluating approximate approaches to study the quantum dynamics of condensed
      phase chemical reactions. Furthermore, the validity of the mapping procedure is
      discussed based on the comparison of the classical dynamics of the original
      atomistic Azzouz-Borgis model and the mapped system-bath model.

PMID- 21842941
TI  - The mean reaction force: a method to study the influence of the environment on
      reaction mechanisms.
AB  - The mean reaction force is introduced as the negative derivative of the free
      energy along a predefined reaction path. In analogy to the reaction force, this
      descriptor allows detailed characterization of different processes of the
      reaction mechanism and the assignment of electronic and structural free energy
      contributions to activation barriers. Due to its free energy dependence, the mean
      reaction force represents a new tool to study the influence of the environment on
      the reaction mechanism. Moreover, it enables the separation of catalytic effects
      in structural and electronic components responsible for the free energy barrier
      reduction of a reaction. To validate the method, the intramolecular proton
      transfer in tryptophan was studied in the gas phase, in aqueous solution and at
      the vacuum-water interface employing molecular dynamics simulation in combination
      with ab initio calculations and the quantum molecular/molecular mechanics (QM/MM)
      methodology. The obtained results were compared to static vacuum and continuum
      calculations. The mean reaction force distinguishes structural rearrangements as
      the dominant free energy component to reach the transition state from the neutral
      form, whereas electronic reorganization predominates the activation of the
      zwitterion in aqueous solution. In addition, it identifies the origin of the
      reduction of the activation barrier for desolvated functional groups at the water
      vacuum interface as the absence of hydrogen bonds which stabilize charge
      delocalized species.

PMID- 21842942
TI  - Molecular dynamics simulation of liquid trimethylphosphine.
AB  - Structural and dynamical properties of liquid trimethylphosphine (TMP),
      (CH(3))(3)P, as a function of temperature is investigated by molecular dynamics
      (MD) simulations. The force field used in the MD simulations, which has been
      proposed from molecular mechanics and quantum chemistry calculations, is able to
      reproduce the experimental density of liquid TMP at room temperature. Equilibrium
      structure is investigated by the usual radial distribution function, g(r), and
      also in the reciprocal space by the static structure factor, S(k). On the basis
      of center of mass distances, liquid TMP behaves like a simple liquid of almost
      spherical particles, but orientational correlation due to dipole-dipole
      interactions is revealed at short-range distances. Single particle and collective
      dynamics are investigated by several time correlation functions. At high
      temperatures, diffusion and reorientation occur at the same time range as
      relaxation of the liquid structure. Decoupling of these dynamic properties starts
      below ca. 220 K, when rattling dynamics of a given TMP molecules due to the cage
      effect of neighbouring molecules becomes important.

PMID- 21842943
TI  - Adsorption of monovalent and divalent cations on planar water-silica interfaces
      studied by optical reflectivity and Monte Carlo simulations.
AB  - Adsorption on planar silica substrates of various monovalent and divalent cations
      from aqueous solution is studied by optical reflectivity. The adsorbed amount is
      extracted by means of a thin slab model. The experimental data are compared with
      grand canonical Monte Carlo titration simulations at the primitive model level.
      The surface excess of charge due to adsorbed cations is found to increase with pH
      and salt concentration as a result of the progressive dissociation of silanol
      groups. The simulations predict, in agreement with experiments, that the surface
      excess of charge from divalent ions is much larger than from monovalent ions. Ion
      ion correlations explain quantitatively the enhancement of surface ionization by
      multivalent cations. On the other hand, the combination of experimental and
      simulation results strongly suggests the existence of a second ionizable site in
      the acidic region. Variation of the distance of closest approach between the ions
      and surface sites captures ion specificity of water-silica interfaces in an
      approximate fashion.

PMID- 21842944
TI  - An empirical dependence of frequency in the oscillatory sorption of H2 and D2 in
      Pd on the first ionization potential of noble gases.
AB  - Oscillatory heat evolution in sorption of H(2) and D(2) in Pd can be induced by
      an admixture of ~10 vol.% of an inert gas (He, Ne, Ar, Kr, or N(2)) to either
      isotope prior to its contact with palladium powder. The oscillations are
      represented in the form of a calorimetric time series, recorded using a gas flow
      through microcalorimeter at the temperatures of 75  degrees C for D(2) and 106 
      degrees C for H(2). For both D(2) and H(2), the oscillation parameters change as
      a function of the kind of inert gas used: the amplitude increases and the
      frequency decreases in passing from He to Kr. An empirical dependence of the
      oscillation frequencies observed for various admixtures and normalized with
      respect to Kr has been found. Accordingly, the frequency is a function of a
      product of the first ionization potential and the square root of atomic mass of
      the inert gas (He, Ne, Ar, Kr, or N(2)). On the other hand, invariance of the
      thermal effects of sorption is evident from the integrated areas under the
      calorimetric time series yielding the molar heats of sorption conserved,
      irrespective of the inert gas admixture. A novel calibration procedure has been
      devised in order to deal with an instability of calibration factor arising in
      desorption of H(2) and D(2) from Pd. A method of dynamic calibration factor made
      it possible to obtain a good agreement between the heats of sorption and
      desorption of both H(2) and D(2) within individual sorption-desorption cycles for
      all inert gas admixtures.

PMID- 21842945
TI  - Reverse nonequilibrium molecular dynamics simulation of thermal conductivity in
      nanoconfined polyamide-6,6.
AB  - A new molecular dynamics simulation method, with coupling to external baths, is
      used to perform equilibrium simulations on polyamide-6,6 trimers nanoconfined
      between graphene surfaces, in equilibrium with the bulk polymer. The method is
      coupled with the reverse nonequilibrium molecular dynamics simulation technique
      to exchange heat in the direction normal to the surfaces. To be able to study the
      effect of confinement on the heat conductance in nanoconfined pores, in this work
      a number of simulations on systems with different pore sizes are done. It is
      concluded that the coefficient of heat conductivity depends on the degree of
      polymer layering between the surfaces and on the pore width. Our results further
      indicate a considerable temperature drop at the interface between the surfaces
      and polymer. The calculated Kapitza lengths depend on the intersurface distance
      and on the layering of the polymer nanoconfined between the surfaces.

PMID- 21842946
TI  - Determining concentration depth profiles in fluorinated networks by means of
      electric force microscopy.
AB  - By means of electric force microscopy, composition depth profiles were measured
      with nanometric resolution for a series of fluorinated networks. By mapping the
      dielectric permittivity along a line going from the surface to the bulk, we were
      able to experimentally access to the fluorine concentration profile. Obtained
      data show composition gradient lengths ranging from 30 nm to 80 nm in the near
      surface area for samples containing from 0.5 to 5 wt. % F, respectively. In
      contrast, no gradients of concentration were detected in bulk. This method has
      several advantages over other techniques because it allows profiling directly on
      a sectional cut of the sample. By combining the obtained results with x-ray
      photoelectron spectroscopy measurements, we were also able to quantify F/C ratio
      as a function of depth with nanoscale resolution.

PMID- 21842947
TI  - Modulation of the thermodynamic, kinetic, and magnetic properties of the hydrogen
      monomer on graphene by charge doping.
AB  - The thermodynamic, kinetic, and magnetic properties of the hydrogen monomer on
      doped graphene layers were studied by ab initio simulations. Electron doping
      heightens the diffusion potential barrier, while hole doping lowers it. However,
      both kinds of dopings heighten the desorption potential barrier. The underlying
      mechanism was revealed by investigating the effect of charge doping on the bond
      strength of graphene and on the electron transfer and the coulomb interaction
      between the hydrogen monomer and graphene. The kinetic properties of H and D
      monomers on doped graphene layers during both the annealing process (annealing
      time t(0) = 300 s) and the constant-rate heating process (heating rate alpha =
      1.0 K/s) were simulated. Macroscopic diffusion of hydrogen monomers on graphene
      can be achieved when the doping-hole density reaches 5.0 * 10(13) cm(-2). Both
      electron and hole dopings linearly reduce the total magnetic moment and exchange
      splitting, which was explained by a simple exchange model. The laws found in this
      work had been generalized to explain many phenomena reported in literature. This
      study can further enhance the understanding of the interaction between hydrogen
      and graphene and was expected to be helpful in the design of hydrogenated
      graphene-based devices.

PMID- 21842948
TI  - 1,2-Dibromoethane on Cu(100): bonding structure and transformation to C2H4.
AB  - Temperature-programmed reaction/desorption, mass spectrometry, reflection
      absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and density
      functional theory calculations have been employed to explore the reaction and
      bonding structure of 1,2-C(2)H(4)Br(2) on Cu(100). Both the trans and gauche
      conformers are found to dissociate by breaking the C-Br bonds on clean Cu(100) at
      115 K, forming C(2)H(4) and Br atoms. Theoretical investigations for the possible
      paths of 1,2-C(2)H(4)Br(2) -> C(2)H(4) + 2Br on Cu(100) suggest that the barriers
      of the trans and gauche molecules are in the ranges of 0-4.2 and 0-6.5 kcal/mol,
      respectively. The C-Br scission temperature of C(2)H(4)Br(2) is much lower than
      that (~170 K) of C(2)H(5)Br on Cu(100). Adsorbed Br atoms can decrease the
      dissociation rate of the 1,2-C(2)H(4)Br(2) molecules impinging the surface. The
      1,2-C(2)H(4)Br(2) molecules adsorbed in the first monolayer are structurally
      distorted. Both the trans and gauche molecules exist in the second monolayer, but
      with no preferential adsorption orientation. However, the trans molecule is the
      predominant species in the third or higher layer formed at 115 K. The layer
      structure is not thermally stable. Upon heating the surface to 150 K, the
      orientation of the trans 1,2-C(2)H(4)Br(2) molecules in the layer changes,
      leading to the rotation of the BrCCBr skeletal plane toward the surface normal on
      average and the considerable growth of the CH(2) scissoring peak. On oxygen
      precovered Cu(100), decomposition of 1,2-C(2)H(4)Br(2) to form C(2)H(4) is
      hampered and no oxygenated hydrocarbons are formed. The presence of the oxygen
      atoms also increases the adsorption energy of the second-layer molecules.

PMID- 21842949
TI  - Ab initio calculations of the reaction pathways for methane decomposition over
      the Cu (111) surface.
AB  - Growth of large-area, few-layer graphene has been reported recently through the
      catalytic decomposition of methane (CH(4)) over a Cu surface at high temperature.
      In this study, we used ab initio calculations to investigate the minimum energy
      pathways of successive dehydrogenation reactions of CH(4) over the Cu (111)
      surface. The geometries and energies of all the reaction intermediates and
      transition states were identified using the climbing image nudged elastic band
      method. The activation barriers for CH(4) decomposition over this Cu surface are
      much lower than those in the gas phase; furthermore, analysis of electron density
      differences revealed significant degrees of charge transfer between the
      adsorbates and the Cu atoms along the reaction path; these features reveal the
      role of Cu as the catalytic material for graphene growth. All the dehydrogenation
      reactions are endothermic, except for carbon dimer (C(2)) formation, which is,
      therefore, the most critical step for subsequent graphene growth, in particular,
      on Cu (111) surface.

PMID- 21842950
TI  - Replica exchange molecular dynamics of the thermodynamics of fibril growth of
      Alzheimer's Abeta42 peptide.
AB  - The growth of amyloid fibrils is studied by replica exchange molecular dynamics
      in an implicit solvent. Our data indicate that extremely long simulation times
      (at least a few hundred ns) are necessary to study the thermodynamics of fibril
      elongation in detail. However some aspects of the aggregation process are already
      accessible on the time scales available in the present study. A peak in the
      specific heat indicates a docking temperature of T(dock) ~ 320 K. Irreversible
      locking requires lower temperatures with the locking temperature estimated as
      T(lock) ~ 280 K. In our simulation the fibril grows from both sides with the C
      terminal of the incoming monomer attaching to the C-terminal of the peptides in
      the fibril forming a beta-sheet on the fibril edge. Our simulation indicates that
      the C-terminal is crucial for aggregation.

PMID- 21842951
TI  - Energy design for protein-protein interactions.
AB  - Proteins bind to other proteins efficiently and specifically to carry on many
      cell functions such as signaling, activation, transport, enzymatic reactions, and
      more. To determine the geometry and strength of binding of a protein pair, an
      energy function is required. An algorithm to design an optimal energy function,
      based on empirical data of protein complexes, is proposed and applied. Emphasis
      is made on negative design in which incorrect geometries are presented to the
      algorithm that learns to avoid them. For the docking problem the search for
      plausible geometries can be performed exhaustively. The possible geometries of
      the complex are generated on a grid with the help of a fast Fourier transform
      algorithm. A novel formulation of negative design makes it possible to
      investigate iteratively hundreds of millions of negative examples while
      monotonically improving the quality of the potential. Experimental structures for
      640 protein complexes are used to generate positive and negative examples for
      learning parameters. The algorithm designed in this work finds the correct
      binding structure as the lowest energy minimum in 318 cases of the 640 examples.
      Further benchmarks on independent sets confirm the significant capacity of the
      scoring function to recognize correct modes of interactions.

PMID- 21842952
TI  - Communication maps computed for homodimeric hemoglobin: computational study of
      water-mediated energy transport in proteins.
AB  - Frequency-resolved communication maps provide a coarse-grained picture of energy
      transport in nanoscale systems. We calculate communication maps for homodimeric
      hemoglobin from Scapharca inaequivalvis and sample them to elucidate energy
      transfer pathways between the binding sites and other parts of the protein with
      focus on the role of the cluster of water molecules at the interface between the
      globules. We complement analysis of communication maps with molecular simulations
      of energy flow. Both approaches reveal that excess energy in one heme flows
      mainly to regions of the interface where early hydrogen bond rearrangements occur
      in the allosteric transition. In particular, energy is carried disproportionately
      by the water molecules, consistent with the larger thermal conductivity of water
      compared to proteins.

PMID- 21842953
TI  - Sequence correlations shape protein promiscuity.
AB  - We predict analytically that diagonal correlations of amino acid positions within
      protein sequences statistically enhance protein propensity for nonspecific
      binding. We use the term "promiscuity" to describe such nonspecific binding.
      Diagonal correlations represent statistically significant repeats of sequence
      patterns where amino acids of the same type are clustered together. The predicted
      effect is qualitatively robust with respect to the form of the microscopic
      interaction potentials and the average amino acid composition. Our analytical
      results provide an explanation for the enhanced diagonal correlations observed in
      hubs of eukaryotic organismal proteomes [J. Mol. Biol. 409, 439 (2011)]. We
      suggest experiments that will allow direct testing of the predicted effect.

PMID- 21842955
TI  - Nucleated polymerization with secondary pathways. II. Determination of self
      consistent solutions to growth processes described by non-linear master
      equations.
AB  - Nucleated polymerisation processes are involved in many growth phenomena in
      nature, including the formation of cytoskeletal filaments and the assembly of
      sickle hemoglobin and amyloid fibrils. Closed form rate equations have, however,
      been challenging to derive for these growth phenomena in cases where secondary
      nucleation processes are active, a difficulty exemplified by the highly non
      linear nature of the equation systems that describe monomer dependent secondary
      nucleation pathways. We explore here the use of fixed point analysis to provide
      self-consistent solutions to such growth problems. We present iterative solutions
      and discuss their convergence behaviour. We establish a range of closed form
      results for linear growth processes, including the scaling behaviours of the
      maximum growth rate and of the reaction end-point. We further show that a self
      consistent approach applied to the master equation of filamentous growth allows
      the determination of the evolution of the shape of the length distribution
      including the mean, the standard deviation, and the mode. Our results highlight
      the power of fixed-point approaches in finding closed form self-consistent
      solutions to growth problems characterised by the highly non-linear master
      equations.

PMID- 21842954
TI  - Nucleated polymerization with secondary pathways. I. Time evolution of the
      principal moments.
AB  - Self-assembly processes resulting in linear structures are often observed in
      molecular biology, and include the formation of functional filaments such as
      actin and tubulin, as well as generally dysfunctional ones such as amyloid
      aggregates. Although the basic kinetic equations describing these phenomena are
      well-established, it has proved to be challenging, due to their non-linear
      nature, to derive solutions to these equations except for special cases. The
      availability of general analytical solutions provides a route for determining the
      rates of molecular level processes from the analysis of macroscopic experimental
      measurements of the growth kinetics, in addition to the phenomenological
      parameters, such as lag times and maximal growth rates that are already
      obtainable from standard fitting procedures. We describe here an analytical
      approach based on fixed-point analysis, which provides self-consistent solutions
      for the growth of filamentous structures that can, in addition to elongation,
      undergo internal fracturing and monomer-dependent nucleation as mechanisms for
      generating new free ends acting as growth sites. Our results generalise the
      analytical expression for sigmoidal growth kinetics from the Oosawa theory for
      nucleated polymerisation to the case of fragmenting filaments. We determine the
      corresponding growth laws in closed form and derive from first principles a
      number of relationships which have been empirically established for the kinetics
      of the self-assembly of amyloid fibrils.

PMID- 21842956
TI  - Nucleated polymerization with secondary pathways. III. Equilibrium behavior and
      oligomer populations.
AB  - We explore the long-time behavior and equilibrium properties of a system of
      linear filaments growing through nucleated polymerisation. We show that the
      length distribution for breakable filaments evolves through two well defined
      limiting cases: first, a steady state distribution determined by the balance of
      breakage and elongation is reached; upon monomer depletion at the end of the
      growth phase, an equilibrium length distribution biased towards smaller filament
      fragments emerges. We furthermore compute the time evolution of the concentration
      of small oligomeric filament fragments. For frangible filaments, oligomers are
      present both at early times and at equilibrium, whereas in the absence of
      fragmentation, oligomers are only present in significant quantities at the
      beginning of the polymerisation reaction. Finally, we discuss the significance of
      these results for the biological consequences of filamentous protein aggregation.

PMID- 21842957
TI  - A test of the bidirectional association between sleep and mood in bipolar
      disorder and insomnia.
AB  - The present study investigates sleep, mood, and the proposed bidirectional
      relationship between the two in psychiatric disorders. Participants with
      interepisode bipolar disorder (n = 49), insomnia (n = 34), and no psychiatric
      history (n = 52) completed seven consecutive days of sleep diaries and mood
      measures. The interepisode bipolar and insomnia participants exhibited greater
      sleep disturbance than the healthy control individuals. Negative mood was equally
      heightened in both interepisode bipolar disorder and insomnia, and there were no
      differences between the three groups in positive mood. Total wake time was
      associated with next morning negative mood in bipolar disorder, whereas evening
      negative mood was associated with subsequent total wake time in both bipolar
      disorder and insomnia. Additionally, positive mood was associated with subsequent
      total wake time for the insomnia group. Results support the theory that
      disruptions in nighttime sleep and daytime mood may be mutually maintaining and
      suggest the potential importance of transdiagnostic or universal processes.

PMID- 21842958
TI  - An invariant dimensional liability model of gender differences in mental disorder
      prevalence: evidence from a national sample.
AB  - Epidemiological studies of categorical mental disorders consistently report that
      gender differences exist in many disorder prevalence rates and that disorders are
      often comorbid. Can a dimensional multivariate liability model be developed to
      clarify how gender impacts diverse, comorbid mental disorders? We pursued this
      possibility in the National Epidemiologic Survey on Alcohol and Related
      Conditions (NESARC; N = 43,093). Gender differences in prevalence were systematic
      such that women showed higher rates of mood and anxiety disorders, and men showed
      higher rates of antisocial personality and substance use disorders. We next
      investigated patterns of disorder comorbidity and found that a dimensional
      internalizing-externalizing liability model fit the data well, where
      internalizing is characterized by mood and anxiety disorders, and externalizing
      is characterized by antisocial personality and substance use disorders. This
      model was gender invariant, indicating that observed gender differences in
      prevalence rates originate from women and men's different average standings on
      latent internalizing and externalizing liability dimensions. As hypothesized,
      women showed a higher mean level of internalizing, while men showed a higher mean
      level of externalizing. We discuss implications of these findings for
      understanding gender differences in psychopathology and for classification and
      intervention.

PMID- 21842959
TI  - Can psychopathic offenders discern moral wrongs? A new look at the
      moral/conventional distinction.
AB  - A prominent view of psychopathic moral reasoning suggests that psychopathic
      individuals cannot properly distinguish between moral wrongs and other types of
      wrongs. The present study evaluated this view by examining the extent to which
      109 incarcerated offenders with varying degrees of psychopathy could distinguish
      between moral and conventional transgressions relative to each other and to
      nonincarcerated healthy controls. Using a modified version of the classic
      Moral/Conventional Transgressions task that uses a forced-choice format to
      minimize strategic responding, the present study found that total psychopathy
      score did not predict performance on the task. Task performance was explained by
      some individual subfacets of psychopathy and by other variables unrelated to
      psychopathy, such as IQ. The authors conclude that, contrary to earlier claims,
      insufficient data exist to infer that psychopathic individuals cannot know what
      is morally wrong.

PMID- 21842960
TI  - The extent and nature of imagery during worry and positive thinking in
      generalized anxiety disorder.
AB  - Clients in treatment for Generalized Anxiety Disorder (GAD) were compared to a
      control group to assess the extent and nature of imagery during worry or while
      thinking about a personally relevant positive future event. Two methods were used
      to assess mentation and were completed in counter balanced order within the worry
      and positive conditions. One method assessed the occurrence of imagery by
      requiring participants to categorize their mentation as verbal thoughts or images
      every 10 s. The other method involved participants estimating the duration of any
      imagery that occurred in the previous 10 s. Imagery during worry occurred less
      often than while thinking about a positive event for both groups, but GAD clients
      had a more pronounced deficit of imagery during worry than the control group.
      Images that occurred were briefer during worry than while thinking about a
      positive future event and were briefer in the GAD than the control group for both
      worry and positive conditions. The results thus confirmed that imagery is less
      common during worry in clients with GAD but also demonstrated that the imagery
      that does occur in GAD is briefer.

PMID- 21842961
TI  - Depression socialization within friendship groups at the transition to
      adolescence: the roles of gender and group centrality as moderators of peer
      influence.
AB  - Tests of interpersonal theories of depression have established that elevated
      depression levels among peers portend increases in individuals' own depressive
      symptoms, a phenomenon known as depression socialization. Susceptibility to this
      socialization effect may be enhanced during the transition to adolescence as the
      strength of peer influence rises dramatically. Socialization of depressive
      symptoms among members of child and adolescent friendship groups was examined
      over a 1-year period among 648 youth in grades six through eight. Sociometric
      methods were utilized to identify friendship groups and ascertain the prospective
      effect of group-level depressive symptoms on youths' own depressive symptoms.
      Hierarchical linear modeling results revealed a significant socialization effect
      and indicated that this effect was most potent for (a) girls and (b) individuals
      on the periphery of friendship groups. Future studies would benefit from
      incorporating child and adolescent peer groups as a developmentally salient
      context for interpersonal models of depression.

PMID- 21842962
TI  - Generalizing the nomological network of psychopathy across populations differing
      on race and conviction status.
AB  - Psychopathy has shown good construct validity in samples of Caucasian inmates.
      However, little is known about how well the nomological network surrounding
      psychopathy generalizes to non-Caucasian and nonincarcerated populations. Using
      longitudinal and concurrent data from the middle sample of the Pittsburgh Youth
      Study, this study demonstrates that the validity of total- and facet-level
      psychopathy is preserved in African American and nonincarcerated samples.
      Specifically, similar patterns of association were obtained for child variables
      (child psychopathy, socioeconomic status, risk status, parenting, delinquency,
      peer delinquency, and impulsivity) and adult variables (children, education,
      incarceration, unemployment, personality, substance use, and antisocial
      personality disorder) across ethnicity and conviction status.

PMID- 21842963
TI  - Anticipatory pleasure predicts motivation for reward in major depression.
AB  - Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or
      experiences, is a cardinal symptom of depression. This deficit in hedonic
      processing has been posited to influence depressed individuals' motivation to
      engage in potentially rewarding experiences. Accumulating evidence indicates that
      hedonic processing is not a unitary construct but rather consists of an
      anticipatory and a consummatory phase. We examined how these components of
      hedonic processing influence motivation to obtain reward in participants
      diagnosed with major depression and in never-disordered controls. Thirty-eight
      currently depressed and 30 never-disordered control participants rated their
      liking of humorous and nonhumorous cartoons and then made a series of choices
      between viewing a cartoon from either group. Each choice was associated with a
      specified amount of effort participants would have to exert before viewing the
      chosen cartoon. Although depressed and control participants did not differ in
      their consummatory liking of the rewards, levels of reward liking predicted
      motivation to expend effort for the rewards only in the control participants; in
      the depressed participants, liking and motivation were dissociated. In the
      depressed group, levels of anticipatory anhedonia predicted motivation to exert
      effort for the rewards. These findings support the formulation that anhedonia is
      not a unitary construct and suggest that, for depressed individuals, deficits in
      motivation for reward are driven primarily by low anticipatory pleasure and not
      by decreased consummatory liking.

PMID- 21842964
TI  - Sleep normalization and decrease in dissociative experiences: evaluation in an
      inpatient sample.
AB  - We conducted a longitudinal study to investigate the relation between sleep
      experiences and dissociative symptoms in a mixed inpatient sample at a private
      clinic evaluated on arrival and at discharge 6 to 8 weeks later. Using
      hierarchical regression analyses and structural equation modeling, we found a
      link between sleep experiences and dissociative symptoms and determined that
      specifically decreases in narcoleptic experiences rather than insomnia accompany
      a reduction in dissociative symptoms. Although sleep improvements were associated
      with a general reduction in psychopathology, this reduction could not fully
      account for the substantial and specific effect that we found for dissociation.
      Our findings are consistent with Watson's (2001) hypothesis that disruptions in
      the sleep-wake cycle lead to intrusions of sleep phenomena into waking
      consciousness, resulting in dissociative experiences. Accordingly, sleep hygiene
      may contribute to the treatment or prevention of dissociative symptoms.

PMID- 21842965
TI  - Discounting of probabilistic rewards is associated with gambling abstinence in
      treatment-seeking pathological gamblers.
AB  - Individuals with addictive disorders, including substance abusers and
      pathological gamblers, discount or devalue rewards delayed in time more than
      controls. Theoretically, preference for probabilistic rewards is directly related
      to gambling, but limited empirical research has examined probabilistic
      discounting in individuals with pathological gambling. This study evaluated
      probability and delay discounting in treatment-seeking pathological gamblers and
      their association with gambling treatment outcomes during and after treatment. At
      time of treatment entry, 226 pathological gamblers completed probability and
      delay discounting tasks. They were then randomized to one of three treatment
      conditions, and gambling behavior was measured throughout treatment and at a 1
      year follow-up assessment. After controlling for possibly confounding variables
      and treatment condition, more shallow probability discounting was associated with
      greater reductions in amounts wagered during treatment and likelihood of gambling
      abstinence at the end of treatment and throughout the follow-up period. No
      associations were noted between delay discounting and gambling treatment
      outcomes. These data suggest that probability discounting may be an important
      construct in understanding pathological gambling and its treatment.

PMID- 21842966
TI  - Developmental emergence of alcohol use disorder symptoms and their potential as
      early indicators for progression to alcohol dependence in a high risk sample: a
      longitudinal study from childhood to early adulthood.
AB  - This study characterized developmental emergence of individual alcohol use
      disorder (AUD) symptoms, and evaluated their ability as early indicators of
      progression into alcohol dependence (AD), conditional upon gender, parental
      alcohol dependence, early onset of drinking, and level of delinquent behavior at
      onset. The two parameters of interest were (a) likelihood of specific AUD symptom
      appearance once drinking has begun, and (b) primacy of symptom appearance as an
      indicator of likelihood for eventual move into diagnosis. We analyzed prospective
      data from a community sample of high risk youth from childhood to early
      adulthood. Symptoms that were at higher probability of being experienced at
      drinking onset and that could serve as good indicators for the early stage of
      disease progression were: persistent desire or unsuccessful efforts to control
      alcohol use (AD4), and continued use despite having persistent or recurrent
      interpersonal problems (AA4). Tolerance (AD1) may serve as an indicator for the
      intermediate stage of progression. Young people tended to be at an elevated risk
      for developing AD6 (activities given up), AD7 (physical/psychological problems),
      and AA3 (legal problems) in later years so these symptoms may be good indicators
      for later stages of progression. In addition to being male, an early onset
      drinker, or high in delinquent behavior, drinkers who experienced AA4 or AD1 as
      first symptoms were at higher risk for progression to AD. We also identified two
      high risk clusters: late onset drinkers with AA4 as first symptom, and children
      of alcoholics with AD1 as first symptom.

PMID- 21842967
TI  - Bidirectional links and concurrent development of parent-child relationships and
      boys' offending behavior.
AB  - This study examined different types of longitudinal associations (i.e.,
      directional links and overlapping developmental changes) between children's
      delinquency and the quality of parent-child relationships from middle childhood
      to late adolescence. We used 10-wave interview data of 503 boys, their primary
      caregivers, and their teachers. Our first aim was to unravel the direction of
      effects between parent-child relationships and children's offending. Cross-lagged
      panel models revealed bidirectional links over time between poorer quality parent
      child relationships and boys' offending across late childhood (age 7-10), early
      adolescence (age 10-13) and middle adolescence (age 13-16). Second, we examined
      the associations between mean changes in delinquency, on the one hand, and mean
      changes in relationship quality, on the other hand. Although parent-child
      relationships improved during childhood, their quality decreased in early
      adolescence and remained stable in middle adolescence. Delinquency increased only
      in middle adolescence. In five out of six models, the slope factors of
      relationship quality and offending were strongly correlated, indicating that
      stronger increases in delinquency were associated with stronger decreases in
      parent-child relationship quality across childhood, early adolescence, and middle
      adolescence. The discussion focuses on the theoretical implications of these two
      types of longitudinal associations.

PMID- 21842968
TI  - Examining the relationship between parenting types and patterns of student
      alcohol-related behavior during the transition to college.
AB  - The present study sought to examine parenting influences on student alcohol use
      through the use of a holistic, person-centered approach in order to accomplish
      three distinct research aims: (a) identify groups of college students with unique
      profiles of perceived parenting characteristics, (b) identify groups of college
      students with unique profiles of alcohol-related correlates, and (c) examine the
      extent to which profiles of perceived parenting characteristics are associated
      with profiles of college alcohol-related risk. A sample of 1,153 first-year
      university students (17-20 years-of-age) was assessed on a host of perceived
      parenting and self-reported alcohol-related items. Four profiles of perceived
      parenting (High Quality, High Monitoring, Anti-Alcohol, Pro-Alcohol) were found
      using latent profile analysis (LPA). Five profiles of student alcohol-related
      characteristics (Abstainers, Past Drinkers, Light Drinkers, High Risk Drinkers,
      Extreme Risk Drinkers) were also found using LPA. Latent transition analysis
      illustrated that students who perceived their parents as belonging to the Pro
      Alcohol profile had much higher probabilities of belonging in the High Risk
      Drinker or Extreme Risk Drinker profiles than students in all other perceived
      parenting profiles. In addition to alcohol-specific parenting characteristics,
      aspects of parent-teen relationship quality may also be integral in the
      prevention of college alcohol misuse. Finally, this study observed complex
      patterns of parenting and alcohol behaviors, such that the profiles could be
      interpreted as qualitatively distinct types of individuals. These unique profiles
      suggest that a targeted approach reflecting the profiles found in the current
      study might greatly enhance prevention program efficacy.

PMID- 21842970
TI  - Clearing the smoke: parental influences on non-smokers' attentional biases to
      smoking-related cues.
AB  - Children who have a parent who smokes are more likely to begin smoking than their
      peers who do not have a family history of smoking behavior. The goal of this
      study was to explore a potential mechanism to explain this relationship. It was
      hypothesized that college-age nonsmokers who have smoking parents would express
      an attentional bias for smoking-related cues relative to those without smoking
      parents. Participants were grouped according to whether one or both of their
      parents smoked (n=32) or neither parent smoked (n=31). A dot-probe paradigm was
      used in which picture pairs that consisted of a smoking-related picture and a
      nonsmoking control picture were displayed for either 500 or 2,000 ms. Each
      picture pair contained either human elements or objects alone. Attentional bias
      was calculated by subtracting reaction times to the smoking stimuli from
      nonsmoking stimuli as a function of content and presentation time. Participants
      with at least one smoking parent demonstrated an attentional bias to smoking
      related pictures relative to control pictures when displayed for 2,000 ms, but
      only when they did not contain human content. Participants without a smoking
      parent showed no attentional bias. These results suggest that college-age
      nonsmokers who have smoking parents may be at-risk for late-onset smoking
      initiation because of their enhanced attention to smoking-related cues.

PMID- 21842969
TI  - Social norms and self-efficacy among heavy using adolescent marijuana smokers.
AB  - Adolescence is a time in which individuals are particularly likely to engage in
      health-risk behaviors, with marijuana being the most prevalent illicit drug used.
      Perceptions of others' use (i.e., norms) have previously been found to be related
      to increased marijuana use. Additionally, low refusal self-efficacy has been
      associated with increased marijuana consumption. This cross-sectional study
      examined the effects of normative perceptions and self-efficacy on negative
      marijuana outcomes for a heavy using adolescent population. A structural equation
      model was tested and supported such that significant indirect paths were present
      from descriptive norms to marijuana outcomes through self-efficacy. Implications
      for prevention and intervention with heavy using adolescent marijuana users are
      discussed.

PMID- 21842971
TI  - Guidelines for the evaluation of dementia and age-related cognitive change.

PMID- 21842972
TI  - Lesbian, gay, and bisexual victimization in the military: an unintended
      consequence of "Don't Ask, Don't Tell"?
AB  - The integration of lesbian, gay, and bisexual (LGB) individuals into the U.S.
      military is a long-standing and politically and socially divisive issue.
      Exclusionary and pseudo-inclusionary policies that restrict openly LGB
      individuals from military service are also of long duration. Yet LGB
      servicemembers have continued to serve covertly in the military for many decades.
      Moreover, political issues and social conventions associated with "Don't Ask,
      Don't Tell" (DADT) have diverted focus from imperative research issues, such as
      LGB servicemembers and incidents of victimization in the military. Research is
      reviewed to evaluate such victimization, which is conceptualized as resulting
      from a convergence of sexual stigma, conservative gender role beliefs, and sexual
      prejudice. DADT, in combination with overarching difficulties intrinsic to sexual
      orientation research, serves to augment LGB victimization and reduce victim
      reports and help seeking. Consequently, there is a deficient evidence base for
      assisting LGB servicemembers and for advancing research, prevention efforts, and
      policy changes. Implications of repealing DADT are discussed, as are future
      directions for LGB military research.

PMID- 21842973
TI  - Effects of message, source, and context on evaluations of employee voice
      behavior.
AB  - The article contained a production-related error. In Table 5, the four values in
      the rows for Study 1 Prosocial motives and Study 1 Constructive voice should have
      been shifted one column to the right, to the Direct and Total Performance
      evaluations columns. All versions of this article have been corrected.] Although
      employee voice behavior is expected to have important organizational benefits,
      research indicates that employees voicing their recommendations for
      organizational change may be evaluated either positively or negatively by
      observers. A review of the literature suggests that the perceived efficacy of
      voice behaviors may be a function of characteristics associated with the (a)
      source, (b) message, and (c) context of the voice event. In this study, we
      manipulated variables from each of these categories based on a model designed to
      predict when voice will positively or negatively impact raters' evaluations of an
      employee's performance. To test our model, we conducted 3 laboratory studies in
      which we manipulated 2 source factors (voicer expertise and trustworthiness), 2
      message factors (recommending a solution and positively vs. negatively framing
      the message), and 2 context factors (timing of the voice event and organizational
      norms for speaking up vs. keeping quiet). We also examined the mediating effects
      of liking, prosocial motives, and perceptions that the voice behavior was
      constructive on the relationships between the source, message, and context
      factors and performance evaluations. Generally speaking, we found that at least
      one of the variables from each category had an effect on performance evaluations
      for the voicer and that most of these effects were indirect, operating through
      one or more of the mediators. Implications for theory and future research are
      discussed.

PMID- 21842974
TI  - The paradox of intragroup conflict: a meta-analysis.
AB  - Since the meta-analysis by De Dreu and Weingart (2003b) on the effects of
      intragroup conflict on group outcomes, more than 80 new empirical studies of
      conflict have been conducted, often investigating more complex, moderated
      relationships between conflict and group outcomes, as well as new types of
      intragroup conflict, such as process conflict. To explore the trends in this new
      body of literature, we conducted a meta-analysis of 116 empirical studies of
      intragroup conflict (n = 8,880 groups) and its relationship with group outcomes.
      To address the heterogeneity across the studies included in the meta-analysis, we
      also investigated a number of moderating variables. Stable negative relationships
      were found between relationship and process conflict and group outcomes. In
      contrast to the results of De Dreu and Weingart, we did not find a strong and
      negative association between task conflict and group performance. Analyses of
      main effects as well as moderator analyses revealed a more complex picture. Task
      conflict and group performance were more positively related among studies where
      the association between task and relationship conflict was relatively weak, in
      studies conducted among top management teams rather than non-top management
      teams, and in studies where performance was measured in terms of financial
      performance or decision quality rather than overall performance.

PMID- 21842975
TI  - Alternative reference points and outcome evaluation: the influence of affect.
AB  - Two studies examined the effect of affective states on decision outcome
      evaluation under the presence or absence of salient alternative reference points.
      Alternative reference points exist when there are 2 possible referents from which
      an outcome can be evaluated, and the outcome is judged as good from the
      perspective of one referent and bad from the perspective of the other. The
      results support a motivational process of evaluating outcomes in which
      individuals select the reference point that allows them to maintain positive mood
      or improve negative mood. Mood measurements taken before and after the task
      revealed that those in positive moods maintained their mood whether or not they
      had alternative reference points in the evaluation of their outcomes. Those in
      negative affective states improved their mood only when there was an alternative
      reference point that allowed the outcome to be compared favorably; when there was
      no such alternative reference point, they maintained their negative mood.

PMID- 21842976
TI  - Motivating proteges' personal learning in teams: a multilevel investigation of
      autonomy support and autonomy orientation.
AB  - This study examined the roles of 3 multilevel motivational predictors in
      proteges' personal learning in teams: an autonomy-supportive team climate,
      mentors' autonomy support, and proteges' autonomy orientation. The authors
      followed 305 proteges in 58 teams for 12 weeks and found that all 3 predictors
      were positively related to the proteges' personal learning in teams and that an
      autonomy-supportive team climate augmented the effects of mentors' autonomy
      support and proteges' autonomy orientation on proteges' personal learning in
      teams. Proteges' personal learning in teams mediated the interactive effects of
      an autonomy-supportive team climate with mentors' autonomy support or proteges'
      autonomy orientation on proteges' behavioral and attitudinal outcomes, including
      their organizational citizenship behaviors and job involvement. The findings of
      this study provide business researchers and practitioners with valuable insights
      into the management of autonomy.

PMID- 21842977
TI  - When does transformational leadership enhance employee proactive behavior? The
      role of autonomy and role breadth self-efficacy.
AB  - Two multisource studies address the interactive effects of personal and
      contextual variables on employees' proactive behavior. In line with previous
      work, we find positive main effects of transformational leadership, role breadth
      self-efficacy, and job autonomy on employee proactive behavior (personal
      initiative in Study 1 and prosocial proactive behavior in Study 2). As expected,
      a 3-way interaction qualifies these main effects: In situations of high autonomy,
      transformational leadership relates positively to proactive behavior for
      individuals high (but not low) on self-efficacy. Vice versa, in situations low on
      job autonomy, transformational leadership relates positively to proactive
      behavior for individuals low (but not high) on self-efficacy. This pattern is
      found both for self-ratings and peer-ratings of employees' proactive behavior in
      Study 1 and for supervisor ratings of such behavior in Study 2.

PMID- 21842978
TI  - Hamsters' (Mesocricetus auratus) memory in a radial maze analog: the role of
      spatial versus olfactory cues.
AB  - The golden hamster's (Mesocricetus auratus) performance on radial maze tasks has
      not been studied a lot. Here we report the results of a spatial memory task that
      involved eight food stations equidistant from the center of a circular platform.
      Each of six male hamsters depleted the food stations along successive choices.
      After each choice and a 5-s retention delay, the hamster was brought back to the
      center of the platform for the next choice opportunity. When only one baited
      station was left, the platform was rotated to evaluate whether olfactory traces
      guided hamsters' choices. Results showed that despite the retention delay
      hamsters performed above chance in searching for food. The choice distributions
      observed during the rotation probes were consistent with spatial memory and could
      be explained without assuming guidance by olfactory cues. The radial maze analog
      we devised could be useful in furthering the study of spatial memory in hamsters.

PMID- 21842979
TI  - Turtles (Pseudemys nelsoni) learn about visual cues indicating food from
      experienced turtles.
AB  - We investigated whether turtles (Pseudemys nelsoni) could learn about a visual
      object cue to obtain food reinforcement by observing conspecifics that had
      learned the task. This study was designed with a three part task which, if
      completed by the observer turtles, would provide evidence of their abilities to
      learn from other turtles using stimulus enhancement, goal emulation, or copying.
      All four P. nelsoni turtles tested after observation of a trained demonstrator,
      whom they had direct access to during the demonstrator training trials, learned
      not only to follow another turtle to the stimulus indicating food, but also, in
      the absence of the demonstrator, to approach the correct stimulus regardless of
      spatial position. Therefore, all four P. nelsoni turtles tested showed evidence
      of stimulus enhancement learning. This is the first experimental study of social
      learning in any aquatic reptile demonstrating that they have the ability to learn
      from conspecifics.

PMID- 21842980
TI  - Paw preference is not affected by postural demand in a nonprimate mammal (Felis
      silvestris catus).
AB  - Previously, it has been thought that handedness is unique to humans. Recently, it
      has been found that hand or paw preferences are common among a variety of
      vertebrate species. Different models have been put forth to describe the
      evolution of primate handedness. In this study we aimed to explore whether these
      models can also be used to predict manual laterality in nonprimate mammalian
      groups. The cat (Felis silvestris catus) is a good nonprimate model for manual
      laterality, as cats frequently use paws to catch and hold prey. Cats were exposed
      to two standardized manual laterality tasks, differing in postural demand.
      Subjects (N = 28) were forced to use either a stable or unstable body posture
      (i.e., sitting or standing vs. vertical clinging) to extract food items from a
      plastic box attached at two different heights. We revealed that cats exhibited
      paw preferences at an individual level with about 40% left, 30% right, 30%
      nonlateralized subjects. Postural demand was linked to task difficulty: the
      unstable body posture was found to be significantly more difficult than the
      stable body posture. However, these differences in postural demand and task
      difficulty did not lead to differences in direction or strength of paw
      preference. Findings suggested that nonprimate mammals differ from primates in
      their sensitivity to task related factors, such as postural demand. Results
      coincide with those of some prosimians, providing support for the hypothesis that
      postural demand and the associated task complexity became influencing factors on
      manual laterality in the course of primate evolution.

PMID- 21842981
TI  - Evidence for kinship information contained in the rhesus macaque (Macaca mulatta)
      face.
AB  - The ability to recognize kin is an important social skill for primates. Humans
      are adept at using facial similarity to recognize likely kin, and there is
      evidence that nonhuman primates are also able to use facial similarity to make
      judgments about kinship. However, if and how nonhuman primate faces actually
      contain kinship information remains unclear. To test whether there is objectively
      measurable facial similarity in related nonhuman primates, we compared facial
      measurements from related (paternal half-sisters) and unrelated adult female
      rhesus macaques (Macaca mulatta). Facial measurements were first summarized into
      5 factors using a principal component analysis. Differences in these factors
      between the faces of related macaques were compared with differences between the
      faces of random unrelated macaques and of age-matched unrelated macaques. The
      difference in facial measurements between related macaques was significantly
      smaller than the difference in facial measurements of either group of unrelated
      macaques, constituting an objective measure of facial similarity in macaque kin.
      These results indicate that kinship information is contained in the rhesus
      macaque face and suggest that nonhuman primates may rely in part on facial
      similarity to distinguish kin.

PMID- 21842982
TI  - Do reef fish, Variola louti and Scarus niger, perform amodal completion? Evidence
      from a field study.
AB  - In terms of visual perception, coral reefs are structurally complex habitats.
      Therefore, visual stimuli that invoke territorial behavior in fish, causing them
      to respond to potential intruders and competitors, may be fragmented. Amodal
      completion was recently shown in a fish species. Here, we presented a mirror
      covered by occluders, with different squared openings arranged in a vertical or a
      horizontal broken line or a checkerboard formation, within their natural
      territories in the reef. Single small openings in the occluders did not trigger
      an attack on the reflected image, while specific configurations of them did so,
      suggesting that fish recognized an intruder in the fragmented image. The results
      suggest the use of amodal completion by fish although other possibilities cannot
      be rejected.

PMID- 21842983
TI  - Megachiropteran bats (Pteropus) utilize human referential stimuli to locate
      hidden food.
AB  - Spontaneous point-following behavior has been considered an indicator of advanced
      social cognition unique to humans. Recently, it has been suggested that a close
      evolutionary relationship with humans could result in similar social skills in
      domesticated species. An alternative view is that the mechanism is not genetic
      domestication alone but instead a combination of phylogenetic and ontogenetic
      variables. Here we test the necessity of phylogenetic domestication by
      investigating the point-following behavior of a captive population of
      nondomesticated megachiropteran bats (Pteropus pumilus, Pteropus rodricensis,
      Pteropus conspicillatus, Pteropus vampyrus). Three of five subjects were highly
      successful in following an unfamiliar human's point to a target location,
      providing the first empirical evidence of cross-species social referencing in
      bats. The three successful bats were all born in captivity and socialized to
      humans early in life, whereas unsuccessful bats were wild-born individuals. This
      study provides evidence that referential point following is not restricted to
      domesticated animals and indicates that early experience may be important.
      Megachiropteran bats may prove to be a useful model for studying social
      behaviors.

PMID- 21842984
TI  - Reformulating and testing the perfectionism model of binge eating among
      undergraduate women: a short-term, three-wave longitudinal study.
AB  - The perfectionism model of binge eating (PMOBE) is an integrative model
      explaining why perfectionism is related to binge eating. This study reformulates
      and tests the PMOBE, with a focus on addressing limitations observed in the
      perfectionism and binge-eating literature. In the reformulated PMOBE, concern
      over mistakes is seen as a destructive aspect of perfectionism contributing to a
      cycle of binge eating via 4 binge-eating maintenance variables: interpersonal
      discrepancies, low interpersonal esteem, depressive affect, and dietary
      restraint. This test of the reformulated PMOBE involved 200 undergraduate women
      studied using a 3-wave longitudinal design. As hypothesized, concern over
      mistakes appears to represent a vulnerability factor for binge eating.
      Bootstrapped tests of mediation suggested concern over mistakes contributes to
      binge eating through binge-eating maintenance variables, and results supported
      the incremental validity of the reformulated PMOBE beyond perfectionistic
      strivings and neuroticism. The reformulated PMOBE also predicted binge eating,
      but not binge drinking, supporting the specificity of this model. The
      reformulated PMOBE offers a framework for understanding how key contributors to
      binge eating work together to generate and to maintain binge eating.

PMID- 21842985
TI  - Can Beck's theory of depression and the response style theory be integrated?
AB  - There are obvious similarities between the cognitive constructs of A. T. Beck's
      (1976) cognitive theory and the response style theory (S. Nolen-Hoeksema & J.
      Morrow, 1991). Different propositions of J. A. Ciesla and J. E. Roberts (2007)
      and S. Lyubomirsky and S. Nolen-Hoeksema (1993, 1995) concerning associations of
      2 response styles, brooding and reflection, with constructs of Beck's cognitive
      theory (schemata, cognitive errors, cognitive triad, automatic thoughts) were
      tested. Model comparisons were based on a 4-week study in which 397 participants
      completed self-report instruments at 2 time points. A model allowing schemata to
      influence brooding and reflection that influence the other cognitive variables of
      Beck's cognitive theory fits the data better than the other integrated models.
      However, although schemata were significant predictors of both response styles,
      neither response style did significantly predict other cognitive variables. A
      comparison of the integrated model with Beck's original cognitive theory revealed
      that Beck's original theory fits the data better than the integrated model,
      whereas both models explain about the same amount of variance. Thus, an
      integration of Beck's theory and the response style theory are not supported.

PMID- 21842986
TI  - Development and initial validation of the inventory of Microaggressions Against
      Black Individuals.
AB  - The present article describes the development and initial validation of the
      Inventory of Microaggressions Against Black Individuals (IMABI) using a sample of
      385 undergraduates who self-identified as Black or African American. The IMABI is
      a 14-item, unidimensional measure of racial microaggressions that captures both
      microinsults and microinvalidations. The present findings support the IMABI as a
      reliable and valid measure of microaggressions that was associated with general
      distress and perceived stress. Importantly, the association between the IMABI and
      psychological adjustment persisted even when social desirability and another
      measure of race-related stress were included in the analyses. Discussion focuses
      on the potential implications of the IMABI for understanding the daily
      experiences and psychological adjustment of Black individuals.

PMID- 21842987
TI  - Longitudinal genetic analysis of anxiety sensitivity.
AB  - Anxiety sensitivity is associated with both anxiety and depression and has been
      shown to be heritable. Little, however, is known about the role of genetic
      influence on continuity and change of symptoms over time. The authors' aim was to
      examine the stability of anxiety sensitivity during adolescence. By using a
      genetically sensitive design, the authors were also able to investigate the
      extent to which genetic and environmental factors influence anxiety sensitivity
      over time. Self-reports of anxiety sensitivity were obtained for over 1,300 twin
      and sibling pairs at 3 time points. Data were analyzed using multivariate genetic
      models. Anxiety sensitivity was moderately heritable at all time points with
      substantial nonshared environmental contributions. Time 1 genetic factors
      accounted for continuity of symptoms at Times 2 and 3. New genetic factors at
      Time 2 also influenced Time 3 symptoms. New nonshared environmental influences
      emerged at each time point. Analysis of a latent factor of trait anxiety
      sensitivity revealed some stable nonshared environmental influences. Genetic
      effects were generally stable over time, with new genetic influences emerging in
      late adolescence. Environmental influences on anxiety sensitivity were, on the
      whole, more time specific; however, some stable environmental influences were
      also found.

PMID- 21842988
TI  - Come rain or come shine: individual differences in how weather affects mood.
AB  - There is a widespread belief that weather affects mood. However, few studies have
      investigated this link, and even less is known about individual differences in
      people's responses to the weather. In the current study, we sought to identify
      weather reactivity types by linking self-reported daily mood across 30 days with
      objective weather data. We identified four distinct types among 497 adolescents
      and replicated these types among their mothers. The types were labeled Summer
      Lovers (better mood with warmer and sunnier weather), Unaffected (weak
      associations between weather and mood), Summer Haters (worse mood with warmer and
      sunnier weather), and Rain Haters (particularly bad mood on rainy days). In
      addition, intergenerational concordance effects were found for two of these
      types, suggesting that weather reactivity may run in the family. Overall, the
      large individual differences in how people's moods were affected by weather
      reconciles the discrepancy between the generally held beliefs that weather has a
      substantive effect on mood and findings from previous research indicating that
      effects of weather on mood are limited or absent.

PMID- 21842989
TI  - Processing orientation and emotion recognition.
AB  - There is evidence that some emotional expressions are characterized by diagnostic
      cues from individual face features. For example, an upturned mouth is indicative
      of happiness, whereas a furrowed brow is associated with anger. The current
      investigation explored whether motivating people to perceive stimuli in a local
      (i.e., feature-based) rather than global (i.e., holistic) processing orientation
      was advantageous for recognizing emotional facial expressions. Participants
      classified emotional faces while primed with local and global processing
      orientations, via a Navon letter task. Contrary to previous findings for identity
      recognition, the current findings are indicative of a modest advantage for face
      emotion recognition under conditions of local processing orientation. When primed
      with a local processing orientation, participants performed both significantly
      faster and more accurately on an emotion recognition task than when they were
      primed with a global processing orientation. The impacts of this finding for
      theories of emotion recognition and face processing are considered.

PMID- 21842990
TI  - Emotional regulation of fertility decision making: what is the nature and
      structure of "baby fever"?
AB  - Baby fever-a visceral physical and emotional desire to have a baby-is well known
      in popular culture, but has not been empirically studied in psychology. Different
      theoretical perspectives suggest that desire for a baby is either superfluous to
      biological sex drives and maternal instincts, a sociocultural phenomenon
      unrelated to biological or evolutionary forces, or an evolved adpatation for
      regulating birth timing, proceptive behavior, and life history trajectories. A
      series of studies (involving 337 undergraduate participants and 853 participants
      from a general population Internet sample) found that: (a) a simple scale measure
      could elicit ratings of desire frequency; (b) these ratings exhibited significant
      sex differences; (c) this sex difference was distinct from a general desire for
      sexual activity; and (d) these findings generalize to a more diverse online
      population. Factor analyses of ratings for desire elicitors/inhibitors identified
      three primary factors underlying baby fever. Baby fever appears to be a real
      phenomenon, with an underlying multifactorial structure.

PMID- 21842991
TI  - Mapping cardiac physiology and parenting processes in maltreating mother-child
      dyads.
AB  - Child maltreatment (CM) lies on an extreme end of the continuum of parenting-at
      risk, and while CM has been linked with a variety of behavioral indicators of
      dysregulation in children, less is known about how physiological markers of
      regulatory capacity contribute to this association. The present study examined
      patterns of mother and child physiological regulation and their relations with
      observed differences in parenting processes during a structured interaction.
      Abusing, neglecting, and non-CM mothers and their 3- to 5-year-old children
      completed a resting baseline and moderately challenging joint task. The
      structural analysis of social behavior was used to code mother-child interactions
      while simultaneous measures of respiratory sinus arrhythmia were obtained.
      Results indicated that physically abusive mothers were more likely to react to
      children's positive bids for autonomy with strict and hostile control, than
      either neglecting or non-CM mothers. CM exposure and quality of maternal
      responding to children's autonomous bids were uniquely associated with lower
      parasympathetic tone in children. Results provide evidence of neurodevelopmental
      associations between early CM exposure, the immediate interactive context of
      parenting, and children's autonomic physiology.

PMID- 21842992
TI  - Cultural influences on positive father involvement in two-parent Mexican-origin
      families.
AB  - A growing body of research documents the importance of positive father
      involvement in children's development. However, research on fathers in Latino
      families is sparse, and research contextualizing the father-child relationship
      within a cultural framework is needed. The present study examined how fathers'
      cultural practices and values predicted their fifth-grade children's report of
      positive father involvement in a sample of 450 two-parent Mexican-origin
      families. Predictors included Spanish- and English-language use, Mexican and
      American cultural values, and positive machismo (i.e., culturally related
      attitudes about the father's role within the family). Positive father involvement
      was measured by the child's report of his or her father's monitoring, educational
      involvement, and warmth. Latent variable regression analyses showed that fathers'
      machismo attitudes were positively related to children's report of positive
      father involvement and that this association was similar across boys and girls.
      The results of this study suggest an important association between fathers'
      cultural values about men's roles and responsibilities within a family and their
      children's perception of positive fathering.

PMID- 21842993
TI  - An introduction to the special section on U.S. military operations: effects on
      military members' partners and children.
AB  - The deployment of U.S. military personnel to global hot spots, whether as
      combatants or as peacekeepers, has increased attention to the psychological well
      being of military personnel and their family members. Despite the growing
      awareness that deployments have reverberating effects on all family members,
      theoretical explanations and empirical research on the impact of deployment on
      couple, family, and child adjustment, factors that serve to protect families from
      the demands of military employment, and effective methods of treating the mental
      health needs of military families are needed. The seven papers in this section
      increase our understanding of how the demands of U.S. military operations impact
      couples, family functioning, parenting, and child psychological adjustment and
      provide an additional resource for mental health professionals who work with
      these families.

PMID- 21842994
TI  - The case for treating depression in military spouses.
AB  - The increased operational tempo associated with current deployments to Operation
      Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) is placing considerable
      strain on military families. Among other sequelae of OIF and OEF deployment,
      findings from recent studies suggest high rates of depression in spouses of
      service members. This review presents a rationale for targeting depression among
      military spouses. It examines how stressors relating to the deployment cycle may
      contribute to depression in spouses and outlines the effects of spousal
      depression on the mental health of service members and their children. Mental
      health services currently available to military spouses as well as barriers to
      their care are also described. Considerations for the adaptation of treatment to
      their unique circumstances and needs are discussed.

PMID- 21842995
TI  - Evaluation of an education day for families of children with obstetrical brachial
      plexus palsy.
AB  - Children with obstetrical brachial plexus palsy may have chronic physical
      impairment in their affected upper extremity. Affected children and their
      families may benefit from psychosocial interventions including therapeutic
      relationships with health professionals, meeting other families living with
      obstetrical brachial plexus palsy, support groups, and social work. One method of
      addressing psychosocial needs is through a support and education day. The purpose
      of this quality improvement project is to evaluate parental perceptions of a
      support and education day called the "Brachial Plexus Family Day." Families of
      children with obstetrical brachial plexus palsy who attended the Brachial Plexus
      Family Day completed a questionnaire to evaluate the different programs offered
      during the day. The families also ranked the importance of different psychosocial
      supports offered in the clinic. Sixty-three out of 69 families completed the
      questionnaire. Each program of the Brachial Plexus Family Day was rated as good
      or excellent by the respondents. Ninety-seven percent of respondents rated
      meeting other families and children with obstetrical brachial plexus palsy as
      helpful supports. Attending a Brachial Plexus Family day event (86%), followed by
      connecting with a doctor (60%), and physical or occupational therapist (59%) were
      the highest ranked supports reported by the families. The parents and caregivers
      that attended the Brachial Plexus Family Day rated the program highly. This group
      also valued the opportunity to connect with other families and children affected
      with the same condition.

PMID- 21842996
TI  - Subliminal activation of social ties moderates cardiovascular reactivity during
      acute stress.
AB  - OBJECTIVE: The quality of one's personal relationships has been reliably linked
      to important physical health outcomes, perhaps through the mechanism of
      physiological stress responses. Most studies of this mechanism have focused on
      whether more conscious interpersonal transactions influence cardiovascular
      reactivity. However, whether such relationships can be automatically activated in
      memory to influence physiological processes has not been determined. The primary
      aims of this study were to examine whether subliminal activation of relationships
      could influence health-relevant physiological processes and to examine this
      question in the context of a more general relationship model that incorporates
      both positive and negative dimensions. METHOD: We randomly assigned participants
      to be subliminally primed with existing relationships that varied in their
      underlying positivity and negativity (i.e., indifferent, supportive, aversive,
      ambivalent). They then performed acute psychological stressors while
      cardiovascular and self-report measures were assessed. RESULTS: Priming negative
      relationships was associated with greater threat, lower feelings of control, and
      higher diastolic blood pressure reactivity during stress. Moreover, priming
      relationships high in positivity and negativity (ambivalent ties) was associated
      with the highest heart rate reactivity and greatest respiratory sinus arrhythmia
      decreases during stress. Exploratory analyses during the priming task itself
      suggested that the effects of negative primes on biological measures were
      prevalent across tasks, whereas the links to ambivalent ties was specific to the
      subsequent stressor task. CONCLUSIONS: These data highlight novel mechanisms by
      which social ties may impact cardiovascular health, and further suggest the
      importance of incorporating both positivity and negativity in the study of
      relationships and physical health.

PMID- 21842997
TI  - Daily sleep quality and mood as predictors of pain in children with juvenile
      polyarticular arthritis.
AB  - OBJECTIVE: Children with arthritis experience frequent pain, but the predictors
      of daily pain variations are largely unidentified. The goal of this study was to
      examine sleep quality as a predictor of pain in children with arthritis and to
      determine whether mood moderates this relationship. METHOD: In this prospective,
      longitudinal study children with polyarticular arthritis (n = 51, ages 8-16
      years) tracked daily symptoms, including sleep quality over 2 months. Self
      reported daily pain intensity, as indicated on a visual analog scale, was used as
      the primary outcome measure in multilevel models. RESULTS: Poorer sleep quality
      was associated with higher next-day pain ratings (p < .01). Mood moderated this
      relationship such that as positive mood increased, the relationship between poor
      sleep quality and high pain weakened (p < .01). Daily pain did not predict
      nightly sleep quality (p > .05). CONCLUSIONS: Sleep quality is an important
      predictor of pain in children with arthritis. These findings add to the growing
      body of literature on the use of daily diaries for analyzing patterns of pain,
      sleep, and mood in children with chronic painful conditions.

PMID- 21842998
TI  - Numbers can be worth a thousand pictures: individual differences in understanding
      graphical and numerical representations of health-related information.
AB  - OBJECTIVE: Informed medical decision making requires comprehending statistical
      information. We aimed to improve the understanding of conveying health-related
      statistical information with graphical representations compared with numerical
      representations. First, we investigated whether the iconicity of representations
      (i.e., their abstractness vs. concreteness) affected comprehension and recall of
      statistical information. Second, we investigated whether graph literacy helps to
      identify individuals who comprehend graphical representations better than
      numerical representations. METHOD: Participants (N = 275) were randomly assigned
      to receive different representations of health-related statistical information,
      ranging from very low iconicity (numbers) to very high iconicity (icon arrays
      including photographs). Comprehension and recall of the information were
      assessed. Additionally, participants rated the accessibility of the information
      and the attractiveness of the representation. Graph literacy was assessed by
      means of a recently developed scale. RESULTS: The only difference between
      representations that affected comprehension and recall was the difference between
      graphics and numbers; the actual level of iconicity of graphics did not matter.
      Individuals with high graph literacy had better comprehension and recall when
      presented with graphics instead of numbers, and they rated graphical information
      as more accessible than numerical information, whereas the reverse was true for
      individuals with low graph literacy, F(4, 185) = 2.60, p = .04, eta(p)(2) = .05,
      and F(4, 245) = 2.71, p = .03, eta(p)(2) = .04, respectively. Both groups judged
      graphical representations as more attractive than numerical representations.
      CONCLUSION: An assessment of graph literacy distinguished individuals who are
      best informed with graphical representations of statistical information from
      those who are better informed with numerical representations.

PMID- 21842999
TI  - Motives for volunteering are associated with mortality risk in older adults.
AB  - OBJECTIVE: The purpose of this study is to examine the effects of motives for
      volunteering on respondents' mortality risk 4 years later. METHODS: Logistic
      regression analysis was used to examine whether motives for volunteering
      predicted later mortality risk, above and beyond volunteering itself, in older
      adults from the Wisconsin Longitudinal Study. Covariates included age, gender,
      socioeconomic variables, physical, mental, and cognitive health, health risk
      behaviors, personality traits, received social support, and actual volunteering
      behavior. RESULTS: Replicating prior work, respondents who volunteered were at
      lower risk for mortality 4 years later, especially those who volunteered more
      regularly and frequently. However, volunteering behavior was not always
      beneficially related to mortality risk: Those who volunteered for self-oriented
      reasons had a mortality risk similar to nonvolunteers. Those who volunteered for
      other-oriented reasons had a decreased mortality risk, even in adjusted models.
      CONCLUSIONS: This study adds to the existing literature on the powerful effects
      of social interactions on health and is the first study to our knowledge to
      examine the effect of motives on volunteers' subsequent mortality. Volunteers
      live longer than nonvolunteers, but this is only true if they volunteer for other
      oriented reasons.

PMID- 21843000
TI  - The relationship between implicit and explicit believability of exercise-related
      messages and intentions.
AB  - OBJECTIVE: This research explored whether implicit or explicit believability of
      exercise advertising predicted attitudes and intentions. It was hypothesized that
      implicit believability would be a stronger predictor of attitudes than explicit
      believability and that implicit believability would predict intentions. METHOD:
      Undergraduate student participants (N = 306) viewed health promotion or
      appearance-based exercise-related advertisements. They completed an implicit
      believability task followed by questionnaires of issue involvement, attention
      paid to the advertisements, explicit believability, exercise attitudes, and
      intentions to exercise. Participants listed 5 thoughts they had when viewing the
      advertisements. Health and appearance models were tested using structural
      equation modeling. Thoughts were coded and valence (negative statements
      subtracted from positive), believability, and motivation indices were created.
      Correlations between indices and model variables were calculated. RESULTS: Both
      models were good fits of the data. In the health condition, explicit
      believability did not predict attitudes or intentions but implicit believability
      predicted attitudes and explicit believability. In the appearance condition,
      implicit believability was negatively related to intentions, but was not related
      to explicit believability or attitudes. There were small positive correlations
      between attitudes and the thought-listing valence index in both conditions.
      CONCLUSIONS: The results indicate that exercise-related health promotion messages
      are believable and that the initial reaction to them coincides with reflective
      attitudes. However, if appearance messages are believed (even if not explicitly),
      the effects may be detrimental. It is important to include implicit measures in
      messaging research as they allow for a more complete understanding of how health
      messages may influence related cognitions.

PMID- 21843001
TI  - The mediating role of partner communication frequency on condom use among African
      American adolescent females participating in an HIV prevention intervention.
AB  - OBJECTIVE: Although effective HIV prevention interventions have been developed
      for adolescents, few interventions have explored whether components of the
      intervention are responsible for the observed changes in behaviors
      postintervention. This study examined the mediating role of partner communication
      frequency on African American adolescent females' condom use postparticipation in
      a demonstrated efficacious HIV risk-reduction intervention. METHODS: As part of a
      randomized controlled trial, African American adolescent females (N = 715), 15-21
      years, seeking sexual health services, completed a computerized interview at
      baseline (prior to intervention) and again 6 and 12 months follow-up post
      intervention participation. The interview assessed adolescents' sexual behavior
      and partner communication skills, among other variables, at each time point.
      Using generalized estimating equation (GEE) techniques, both logistic and linear
      regression models were employed to test mediation over the 12-month follow-up
      period. Additional tests were conducted to assess the significance of the
      mediated models. RESULTS: Mediation analyses observed that partner communication
      frequency was a significant partial mediator of both proportion of condom
      protected sex acts (p = .001) and consistent condom use (p = .001). CONCLUSION:
      Partner communication frequency, an integral component of this HIV intervention,
      significantly increased as a function of participating in the intervention,
      partially explaining the change in condom use observed 12 months
      postintervention. Understanding what intervention components are associated with
      behavior change is important for future intervention development.

PMID- 21843002
TI  - Masking misfit in confirmatory factor analysis by increasing unique variances: a
      cautionary note on the usefulness of cutoff values of fit indices.
AB  - Fit indices are widely used in order to test the model fit for structural
      equation models. In a highly influential study, Hu and Bentler (1999) showed that
      certain cutoff values for these indices could be derived, which, over time, has
      led to the reification of these suggested thresholds as "golden rules" for
      establishing the fit or other aspects of structural equation models. The current
      study shows how differences in unique variances influence the value of the global
      chi-square model test and the most commonly used fit indices: Root-mean-square
      error of approximation, standardized root-mean-square residual, and the
      comparative fit index. Using data simulation, the authors illustrate how the
      value of the chi-square test, the root-mean-square error of approximation, and
      the standardized root-mean-square residual are decreased when unique variances
      are increased although model misspecification is present. For a broader
      understanding of the phenomenon, the authors used different sample sizes, number
      of observed variables per factor, and types of misspecification. A theoretical
      explanation is provided, and implications for the application of structural
      equation modeling are discussed.

PMID- 21843003
TI  - Marginal mean weighting through stratification: a generalized method for
      evaluating multivalued and multiple treatments with nonexperimental data.
AB  - Propensity score matching and stratification enable researchers to make
      statistical adjustment for a large number of observed covariates in
      nonexperimental data. These methods have recently become popular in psychological
      research. Yet their applications to evaluations of multi-valued and multiple
      treatments are limited. The inverse-probability-of-treatment weighting method,
      though suitable for evaluating multi-valued and multiple treatments, often
      generates results that are not robust when only a portion of the population
      provides support for causal inference or when the functional form of the
      propensity score model is misspecified. The marginal mean weighting through
      stratification (MMW-S) method promises a viable nonparametric solution to these
      problems. By computing weights on the basis of stratified propensity scores, MMW
      S adjustment equates the pretreatment composition of multiple treatment groups
      under the assumption that unmeasured covariates do not confound the treatment
      effects given the observed covariates. Analyzing data from a weighted sample,
      researchers can estimate a causal effect by computing the difference between the
      estimated average potential outcomes associated with alternative treatments
      within the analysis of variance framework. After providing an intuitive
      illustration of the theoretical rationale underlying the weighting method for
      causal inferences, the article demonstrates how to apply the MMW-S method to
      evaluations of treatments measured on a binary, ordinal, or nominal scale
      approximating a completely randomized experiment; to studies of multiple
      concurrent treatments approximating factorial randomized designs; and to
      moderated treatment effects approximating randomized block designs. The analytic
      procedure is illustrated with an evaluation of educational services for English
      language learners attending kindergarten in the United States.

PMID- 21843004
TI  - Memory functioning in children and adolescents with autism.
AB  - OBJECTIVE: Memory functioning in children and adolescents ages 5-19 with autism
      (n = 50) and typically developing controls (n = 36) was assessed using a clinical
      assessment battery, the Test of Memory and Learning (TOMAL). METHOD: Participant
      groups were statistically comparable in age, nonverbal IQ, handedness, and head
      circumference, and were administered the TOMAL. RESULTS: Test performance on the
      TOMAL demonstrated broad differences in memory functioning in the autism group,
      across multiple task formats, including verbal and nonverbal, immediate and
      delayed, attention and concentration, sequential recall, free recall, associative
      recall, and multiple-trial learning memory. All index and nearly all subtest
      differences remained significant even after comparing a subset of the autism
      group (n = 36) and controls that were matched for verbal IQ (p > .05). However,
      retention of previously remembered information after a delay was similar in
      autism and controls. CONCLUSIONS: These findings indicate that performance on
      measures of episodic memory is broadly reduced in autism, and support the
      conclusion that information encoding and organization, possibly due to
      inefficient cognitive processing strategies, rather than storage and retrieval,
      are the primary factors that limit memory performance in autism.

PMID- 21843006
TI  - Age effects in emotional prospective memory: cue valence differentially affects
      the prospective and retrospective component.
AB  - While first studies suggested that emotional task material may enhance
      prospective memory performance in young and older adults, the extent and
      mechanisms of this effect are under debate. The authors explored possible
      differential effects of cue valence on the prospective and retrospective
      component of prospective memory in young and older adults. Forty-five young and
      41 older adults performed a prospective memory task in which emotional valence of
      the prospective memory cue was manipulated (positive, negative, neutral). The
      multinomial model of event-based prospective memory was used to analyze effects
      of valence and age on the two prospective memory components separately. Results
      revealed an interaction indicating that age differences were smaller in both
      emotional valence conditions. For older adults positive cues improved the
      prospective component, while negative cues improved the retrospective component.
      No main effect of valence was found for younger adults on an overt accuracy
      measure, but model-based analyses showed that the retrospective component was
      enhanced in the positive compared with the negative cue condition. The study
      extends the literature in demonstrating that processes underlying emotional
      effects on prospective memory may differ depending on valence and age.

PMID- 21843005
TI  - Anger and sadness in response to an emotionally neutral film: evidence for age
      specific associations with well-being.
AB  - When the association between emotion and well-being is being considered, positive
      emotions usually come to mind. However, negative emotions serve important
      adaptive functions and particular negative emotions may be especially adaptive at
      different stages of adult development. We examined the associations between self
      reported negative emotions in response to an emotionally neutral, thematically
      ambiguous film and subjective well-being among 76 young (age 20-29), 73 middle
      aged (age 40-49), and 73 older (age 60-69) adults. Results indicated that higher
      self-reported anger in response to the film was associated with higher well-being
      for middle-aged adults, but not for young and older adults. Higher self-reported
      sadness in response to the film was associated with higher well-being for older
      adults, but not for young and middle-aged adults. These findings were stronger
      for cognitive well-being (i.e., satisfaction with life) than for affective well
      being (i.e., ratio of dispositional positive to negative affect) and were
      specific to these emotions (not found for self-reported disgust or fear) and to
      the emotionally neutral film (not found for sad or disgusting films). Results are
      discussed in terms of the functions that anger and sadness are thought to serve
      and the control opportunities afforded in midlife and late life that render these
      functions differentially adaptive.

PMID- 21843007
TI  - Age-related differences in interhemispheric visuomotor integration measured by
      the redundant target effect.
AB  - Presentation of bilateral redundant visual stimuli produces faster reaction times
      (RT) than presentation of a single unilateral stimulus; an effect known as the
      redundant target effect (RTE; Miller, 1982), and is a means of testing
      interhemispheric visuomotor integration (Ouimet, 2009). RTEs that exceed
      expectations, based on Miller's race model of inequality (RMI), are referred to
      as "enhanced RTEs" and imply neural coactivation. Paradoxically, enhanced RTEs
      are observed in cases of corpus callosum disruption. The Hemispheric Coactivation
      Hypothesis accounts for this paradox by positing that bihemispheric processing
      occurs to both unilateral and bilateral stimuli in the normal brain, but occurs
      only with bilateral stimuli in the disconnected brain. Neuroimaging has revealed
      decreases in the microstructural integrity of the corpus callosum with age (Ota
      et al., 2006), but research investigating the bilateral RTE in healthy older
      individuals is lacking. The present study investigated the bilateral RTE in
      healthy younger and healthy older adults using simple RT and choice RT tasks. Our
      prediction that older individuals would show significantly larger RTEs than
      younger individuals was found to be true for both tasks. Tests of the RMI
      produced little evidence for coactivation. The crossed-uncrossed difference,
      generally used as a means of testing visuomotor interhemispheric transfer, was
      also investigated, but no age effects were found. The observation of greater RTE
      in age is congruent with the Hemispheric Coactivation hypothesis (Miller, 2004)
      in which callosal disconnection is associated with increased RTE.

PMID- 21843008
TI  - The role of source memory in older adults' recollective experience.
AB  - Younger adults' "remember" judgments are accompanied by better memory for the
      source of an item than "know" judgments. Furthermore, remember judgments are not
      merely associated with better memory for individual source features but also with
      bound memory for multiple source features. However, older adults, independent of
      their subjective memory experience, are generally less likely to "bind" source
      features to an item and to each other in memory (i.e., the associative deficit).
      In two experiments, we tested whether memory for perceptual source features,
      independently or bound, is also the basis for older adults' remember responses or
      if their associative deficit leads them to base their responses on other types of
      information. The results suggest that retrieval of perceptual source features,
      individually or bound, forms the basis for younger but not for older adults'
      remember judgments even when the overall level of memory for perceptual sources
      is closely equated (Experiment 1) and when attention is explicitly directed to
      the source information at encoding (Experiment 2).

PMID- 21843009
TI  - Estradiol and progesterone modify the effects of the serotonin reuptake
      transporter polymorphism on serotonergic responsivity to citalopram.
AB  - Individual vulnerability to psychopathologies is linked to a number of genetic
      polymorphisms including the serotonin transporter (5HTT) promoter polymorphic
      region (5HTTLPR). A single copy of the short variant (s-variant) allele of
      5HTTLPR confers increased susceptibility to anxiety disorders and depression and
      decreased efficacy of serotonin-releasing agents in pharmacotherapy compared to
      the homozygous long 5HTTLPR variant (l/L). The data suggesting that the 5HTTLPR
      polymorphism modulates the efficacy of serotonin-releasing agents in
      pharmacotherapy is inconsistent. Other factors such as age, gender, and hormonal
      status could interact with 5HTTLPR genotype to affect individual physiological
      and behavioral responses to serotonin reuptake inhibitors such as citalopram.
      Indeed, estradiol and progesterone, the primary female steroid hormones, exert an
      array of effects on the serotonergic system, including 5HTT expression. The
      present study used ovariectomized female rhesus monkeys to determine the
      interaction between the 5HTTLPR polymorphism and the effects of midfollicular
      levels of estradiol and luteal levels of progesterone on serotonergic
      responsivity to acute citalopram administration. The increase in serum prolactin,
      a surrogate measure of serotonin activity, following citalopram administration
      was significantly larger in l/L females than in s-variant females over the course
      of two hours during concurrent estradiol and progesterone hormone replacement
      only. These data suggest that ovarian function and the 5HTTLPR polymorphism
      interact to gate serotonergic reactivity in females, suggesting that clinicians
      should be aware of the ovarian status and 5HTTLPR genotype of women when
      considering serotonergic pharmacotherapy in women.

PMID- 21843010
TI  - Psychomotor stimulant effects of cocaine in rats and 15 mouse strains.
AB  - Relative to intravenous drug self-administration, locomotor activity is easier to
      measure with high throughput, particularly in mice. Therefore its potential to
      predict differences in self-administration between genotypes (e.g., targeted
      mutations, recombinant inbred strains) is appealing, but such predictive value is
      unverified. The main goal of this study was to evaluate the utility of the
      locomotor assay for accurately predicting differences in cocaine self
      administration. A second goal was to evaluate any correlation between activity in
      a novel environment, and cocaine-induced hyperactivity, between strains. We
      evaluated locomotor activity in male and female Sprague-Dawley rats and 15 mouse
      strains (129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ,
      C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, and outbred Swiss Webster
      and CD-1/ICR), as well as cocaine self-administration in BALB substrains. All but
      BALB/cJ mice showed locomotor habituation and significant cocaine-induced
      hyperactivity. BALB/cJ mice also failed to self-administer cocaine. BALB/cByJ
      mice showed modest locomotor habituation, cocaine-induced locomotion, and cocaine
      self-administration. As previously reported, female rats showed greater cocaine
      induced locomotion than males, but this was only observed in one of 15 mouse
      strains (FVB/NJ), and the reverse was observed in two strains (129X1/SvJ,
      BALB/cByJ). The intriguing phenotype of the BALB/cJ strain may indicate some
      correlation between all-or-none locomotion in a novel environment, and stimulant
      and reinforcing effects of cocaine. However, neither novelty- nor cocaine-induced
      activity offered a clear prediction of relative reinforcing effects among
      strains. Additionally, these results should aid in selecting mouse strains for
      future studies in which relative locomotor responsiveness to psychostimulants is
      a necessary consideration.

PMID- 21843011
TI  - Psychomotor stimulation by dopamine D1-like but not D2-like agonists in most
      mouse strains.
AB  - Many neurological and psychiatric disorders are treated with dopamine modulators.
      Studies in mice may reveal genetic factors underlying those disorders or
      responsiveness to various treatments, and species and strain differences both
      complicate the use of mice and provide valuable tools. We evaluated psychomotor
      effects of the dopamine D1-like agonist R-6-Br-APB and the dopamine D2-like
      agonist quinelorane using a locomotor activity procedure in 15 mouse strains
      (inbred 129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ,
      C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, outbred Swiss Webster, and
      CD-1) and Sprague-Dawley rats, using groups of both females and males. Both D1
      and D2 stimulation produced hyperactivity in the rats, and surprisingly, only two
      mouse strains were similar in that regard (C3H/HeJ, SPRET/EiJ). In contrast, the
      majority of mouse strains exhibited hyperactivity only with D1 stimulation,
      whereas D2 stimulation had no effect or decreased activity. BALB substrains, A/J
      and FVB/NJ mice showed only decreased activity after either D1 or D2 stimulation.
      CAST/EiJ mice exhibited hyperactivity exclusively with D2 stimulation. Sex
      differences were observed but no systematic trend emerged: For example, of the
      five strains in which a main factor of sex was identified for the stimulant
      effects of the D1 agonist, responsiveness was greatest in females in three of
      those strains and in males in two of those strains. These results should aid in
      the selection of mouse strains for future studies in which D1 or D2
      responsiveness is a necessary consideration in the experimental design.

PMID- 21843012
TI  - Attitudes toward emotions.
AB  - The present work outlines a theory of attitudes toward emotions, provides a
      measure of attitudes toward emotions, and then tests several predictions
      concerning relationships between attitudes toward specific emotions and emotional
      situation selection, emotional traits, emotional reactivity, and emotion
      regulation. The present conceptualization of individual differences in attitudes
      toward emotions focuses on specific emotions and presents data indicating that 5
      emotions (anger, sadness, joy, fear, and disgust) load on 5 separate attitude
      factors (Study 1). Attitudes toward emotions predicted emotional situation
      selection (Study 2). Moreover, attitudes toward approach emotions (e.g., anger,
      joy) correlated directly with the associated trait emotions, whereas attitudes
      toward withdrawal emotions (fear, disgust) correlated inversely with associated
      trait emotions (Study 3). Similar results occurred when attitudes toward emotions
      were used to predict state emotional reactivity (Study 4). Finally, attitudes
      toward emotions predicted specific forms of emotion regulation (Study 5).

PMID- 21843013
TI  - Buyer's remorse or missed opportunity? Differential regrets for material and
      experiential purchases.
AB  - Previous research has established that experiential purchases tend to yield
      greater enduring satisfaction than material purchases. The present work suggests
      that this difference in satisfaction is paralleled by a tendency for material and
      experiential purchases to differ in the types of regrets they elicit. In 5
      studies, we find that people's material purchase decisions are more likely to
      generate regrets of action (buyer's remorse) and their experiential purchase
      decisions are more likely to lead to regrets of inaction (missed opportunities).
      These results were not attributable to differences in the desirability of or
      satisfaction provided by the two purchase types. Demonstrating the robustness of
      this effect, we found that focusing participants on the material versus
      experiential properties of the very same purchase was enough to shift its
      dominant type of regret. This pattern of regret is driven by the tendency for
      experiences to be seen as more singular--less interchangeable--than material
      purchases; interchangeable goods tend to yield regrets of action, whereas
      singular goods tend to yield regrets of inaction.

PMID- 21843014
TI  - Seeking security or growth: a regulatory focus perspective on motivations in
      romantic relationships.
AB  - Using a multimethod approach, we examined how regulatory focus shapes people's
      perceptual, behavioral, and emotional responses in different situations in
      romantic relationships. We first examined how chronic regulatory focus affects
      romantic partners' support perceptions and problem-solving behaviors while they
      were engaged in a conflict resolution discussion (Study 1). Next, we
      experimentally manipulated regulatory focus and tested its effects on partner
      perceptions when individuals recalled a prior conflict resolution discussion
      (Study 2). We then examined how chronic regulatory focus influences individuals'
      emotional responses to hypothetical relationship events (Study 3) and identified
      specific partner behaviors to which people should respond with regulatory goal
      congruent emotions (Study 4). Strongly prevention-focused people perceived their
      partners as more distancing and less supportive during conflict (Studies 1 and
      2), approached conflict resolution by discussing the details related to the
      conflict (Study 1), and experienced a negative relationship outcome with more
      agitation (Study 3). Strongly promotion-focused people perceived their partners
      as more supportive and less distancing (Studies 1 and 2), displayed more creative
      conflict resolution behavior (Study 1), and experienced a negative relationship
      outcome with more sadness and a favorable outcome with more positive emotions
      (Study 3). In Study 4, recalling irresponsible and responsible partner behaviors
      was associated with experiencing more prevention-focused emotions, whereas
      recalling affectionate and neglectful partner behaviors was associated with more
      promotion-focused emotions. The findings show that regulatory focus and approach
      avoidance motivations influence certain interpersonal processes in similar ways,
      but regulatory focus theory also generates novel predictions on which approach
      avoidance models are silent.

PMID- 21843015
TI  - Residential mobility breeds familiarity-seeking.
AB  - Why are American landscapes (e.g., housing developments, shopping malls) so
      uniform, despite the well-known American penchant for independence and
      uniqueness? We propose that this paradox can be explained by American mobility:
      Residential mobility fosters familiarity-seeking and familiarity-liking, while
      allowing individuals to pursue their personal goals and desires. We reason that
      people are drawn to familiar objects (e.g., familiar, national chain stores) when
      they move. We conducted 5 studies to test this idea at the levels of society,
      individuals, and situations. We found that (a) national chain stores do better in
      residentially mobile places than in residentially stable places (controlling for
      other economic and demographic factors; Study 1); (b) individuals who have moved
      a lot prefer familiar, national chain stores to unfamiliar stores (Studies 2a and
      2b); and (c) a residential mobility mindset enhances the mere exposure and
      familiarity-liking effect (Studies 4 and 5). In Study 5, we demonstrated that the
      link between mobility and familiarity-liking was mediated by anxiety evoked by
      mobility.

PMID- 21843016
TI  - The buffering effect of resilience on depression among individuals with spinal
      cord injury: a structural equation model.
AB  - OBJECTIVE: To translate the theoretical constructs from a model of resilience
      into a structural equation model and evaluate relationships among the model's
      theoretical constructs associated with resilience and the occurrence of
      depressive symptoms. DESIGN: Quantitative descriptive research design using
      structural equation modeling (SEM). PARTICIPANTS: Two-hundred and fifty-five
      individuals with SCI recruited from the Canadian Paraplegic Association (CPA).
      OUTCOME MEASURES: Outcome was measured by the Center for Epidemiologic Studies
      Depression Scale. RESULTS: The resilience model fit the data relatively well:
      chi2 (200, N = 255) = 451.57, p < .001; chi2/df = 2.26; CFI = .92, RMSEA = 0.070
      (90% CI: 0.062-0.079), explaining 77% of the variance in depressive
      symptomatology. Severity of SCI-related stressors significantly influenced
      perceived stress (beta = .60) and perceived stress, in turn, affected depressive
      symptoms (beta = .66), characteristics of resilience (beta = -.43), and social
      support (beta = -.26). The resilience characteristics had an inverse relationship
      with depressive symptoms (beta = -.29). No direct relationship was found between
      severity of SCI-related stressors and depressive symptoms. CONCLUSIONS: Findings
      provide support for the resilience model and suggests characteristics of
      resilience "buffer" the perceptions of stress on depressive symptoms. The
      resilience model may be useful to guide clinical interventions designed to
      improve the mental health of individuals with SCI.

PMID- 21843017
TI  - The effects of group monitoring on fatigue-related einstellung during
      mathematical problem solving.
AB  - Fatigue resulting from sleep deficit can lead to decreased performance in a
      variety of cognitive domains and can result in potentially serious accidents. The
      present study aimed to test whether fatigue leads to increased Einstellung (low
      levels of cognitive flexibility) in a series of mathematical problem-solving
      tasks. Many situations involving fatigue and problem solving also involve people
      working in teams. However, little research has considered the role of social
      processes in managing the effects of fatigue. Research into the group monitoring
      hypothesis suggests that membership in a team can offset the effects of impairing
      factors such as fatigue upon performance. Thus, the present study also aimed to
      test whether group membership exacerbates or ameliorates the negative effects of
      fatigue. During the course of a weekend military training exercise, participants
      (N = 171) attempted to solve a series of problems either alone or in a team, and
      while either reasonably alert (nonfatigued) or fatigued through sleep deficit.
      Fatigued problem solvers working alone showed increased Einstellung. In contrast,
      and in line with the group monitoring hypothesis, teams of fatigued problem
      solvers did not experience increased Einstellung. The present study also showed
      that teams with a group member who was relatively less fatigued experienced less
      Einstellung than other groups. These effects persisted even once participants
      were cued toward more direct strategies. These findings highlight the risk of
      Einstellung when fatigued and also the importance of team membership with
      reference to problem solving in an occupational context.

PMID- 21843018
TI  - Response latency as a predictor of the accuracy of children's reports.
AB  - Researchers have explored various diagnostic cues to the accuracy of information
      provided by child eyewitnesses. Previous studies indicated that children's
      confidence in their reports predicts the relative accuracy of these reports, and
      that the confidence-accuracy relationship generally improves as children grow
      older. In this study, we examined the added contribution of response latency to
      the prediction of children's accuracy over and above that of confidence ratings.
      In Experiments 1 and 2, 2nd and 5th graders studied picture-event pairs and were
      tested using forced-choice, 2-alternative, or 5-alternative questions. In
      Experiment 3, children watched a slideshow depicting a story and were tested by 5
      alternative questions about story details. The children indicated their
      confidence in each response, and response latency was measured. The results of
      all experiments suggested that children in both age groups relied on response
      latency as a cue for confidence, and this reliance contributed to the success
      with which they monitored the accuracy of their reports. When the test format was
      easy (Experiment 1), 2nd graders were as accurate as 5th graders in monitoring
      the accuracy of their answers, and the latency of their responses was no less
      predictive of accuracy. When the task was more difficult, age differences
      emerged. Nevertheless, in all experiments and for both age groups, response
      latency was found to have added value for predicting accuracy over and above that
      of confidence. Theoretical and practical implications of these findings for
      predicting the accuracy of children's reports are discussed.

PMID- 21843019
TI  - Context-gated statistical learning and its role in visual-saccadic decisions.
AB  - Adaptive behavior in a nonstationary world requires humans to learn and track the
      statistics of the environment. We examined the mechanisms of adaptation in a
      nonstationary environment in the context of visual-saccadic inhibition of return
      (IOR). IOR is adapted to the likelihood that return locations will be refixated
      in the near future. We examined 2 potential learning mechanisms underlying
      adaptation: (a) a local tracking or priming mechanism that facilitates behavior
      that is consistent with recent experience and (b) a mechanism that supports
      retrieval of knowledge of the environmental statistics based on the contextual
      features of the environment. Participants generated sequences of 2 saccadic eye
      movements in conditions where the probability that the 2nd saccade was directed
      back to the previously fixated location varied from low (.17) to high (.50). In
      some conditions, the contingency was signaled by a contextual cue (the shape of
      the movement cue). Adaptation occurred in the absence of contextual signals but
      was more pronounced in the presence of contextual cues. Adaptation even occurred
      when different contingencies were randomly intermixed, showing the parallel
      formation of multiple associations between context and statistics. These findings
      are accounted for by an evidence accumulation framework in which the resting
      baseline of decision alternatives is adjusted on a trial-by-trial basis. This
      baseline tracks the subjective prior beliefs about the behavioral relevance of
      the different alternatives and is updated on the basis of the history of recent
      events and the contextual features of the current environment.

PMID- 21843020
TI  - Success modulates consolidation of a visuomotor adaptation task.
AB  - Consolidation is a time-dependent process that is responsible for the storage of
      information in long-term memory. As such, it plays a crucial role in motor
      learning. Prior research suggests that some consolidation processes are triggered
      only when the learner experiences some success during practice. In the present
      study, we tested whether consolidation processes depend on the objective
      performance of the learner or on the learner's subjective evaluation of his or
      her own performance (i.e., how successful the learner believes he or she is).
      Four groups of participants performed 2 sessions of a visuomotor adaptation task
      for which they had to learn a new internal model of limb kinematics; these
      sessions were either 5 min or 24 hr apart. The task was identical for all
      participants, but each group was given a difficult or an easy objective that
      affected the participants' evaluation of their own performance during the initial
      practice session. All groups adapted their movements similarly to the rotation of
      the visual feedback during the first session. However, when retested the
      following day, participants who had a 24-hr rest interval and had initially
      experienced success performed significantly better than those who did not feel
      successful or who were given a 5-min rest interval. Our results indicate that a
      certain level of subjective success must be experienced to trigger certain
      consolidation processes.

PMID- 21843021
TI  - Consistency of handedness, regardless of direction, predicts baseline memory
      accuracy and potential for memory enhancement.
AB  - Research has shown that consistently right-handed individuals have poorer memory
      than do inconsistently right- or left-handed individuals under baseline
      conditions but more reliably exhibit enhanced memory retrieval after making a
      series of saccadic eye movements. From this it could be that consistent versus
      inconsistent handedness, regardless of left/right direction, is an important
      individual difference factor in memory. Or, more specifically, it could be the
      presence or absence of consistent right-handedness that matters for memory. To
      resolve this ambiguity, we compared consistent and inconsistent left- and right
      handers on associative recognition tests taken after saccades or a no-saccades
      control activity. Consistent-handers exhibited poorer memory than did
      inconsistent-handers following the control activity, and saccades enhanced
      retrieval for consistent-handers only. Saccades impaired retrieval for
      inconsistent-handers. None of these effects depended on left/right direction.
      Hence, this study establishes handedness consistency, regardless of direction, as
      an important individual difference factor in memory.

PMID- 21843022
TI  - Polarity correspondence in metaphor congruency effects: structural overlap
      predicts categorization times for bipolar concepts presented in vertical space.
AB  - Previous research has shown that words presented on metaphor congruent locations
      (e.g., positive words UP on the screen and negative words DOWN on the screen) are
      categorized faster than words presented on metaphor incongruent locations (e.g.,
      positive words DOWN and negative words UP). These findings have been explained in
      terms of an interference effect: The meaning associated with UP and DOWN vertical
      space can automatically interfere with the categorization of words with a
      metaphorically incongruent meaning. The current studies test an alternative
      explanation for the interaction between the vertical position of abstract
      concepts and the speed with which these stimuli are categorized. Research on
      polarity differences (basic asymmetries in the way dimensions are processed)
      predicts that +polar endpoints of dimensions (e.g., positive, moral, UP) are
      categorized faster than -polar endpoints of dimensions (e.g., negative, immoral,
      DOWN). Furthermore, the polarity correspondence principle predicts that stimuli
      where polarities correspond (e.g., positive words presented UP) provide an
      additional processing benefit compared to stimuli where polarities do not
      correspond (e.g., negative words presented UP). A meta-analysis (Study 1) shows
      that a polarity account provides a better explanation of reaction time patterns
      in previous studies than an interference explanation. An experiment (Study 2)
      reveals that controlling for the polarity benefit of +polar words compared to 
      polar words did not only remove the main effect of word polarity but also the
      interaction between word meaning and vertical position due to polarity
      correspondence. These results reveal that metaphor congruency effects should not
      be interpreted as automatic associations between vertical locations and word
      meaning but instead are more parsimoniously explained by their structural overlap
      in polarities.

PMID- 21843023
TI  - On the existence of semantic working memory: evidence for direct semantic
      maintenance.
AB  - Despite widespread acknowledgment of the importance of online semantic
      maintenance, there has been astonishingly little work that clearly establishes
      this construct. We review the extant work relevant to short-term retention of
      meaning and show that, although consistent with semantic working memory, most
      data can be accommodated in other ways. Using a new concurrent probe paradigm, we
      then report experiments that implicate a semantic maintenance capacity that is
      independent of phonological or visual maintenance that may build on a mechanism
      of direct semantic maintenance. Experiments 1 through 5 established that while
      subjects maintain the meaning of a word, a novel delay-period marker of semantic
      retention, the semantic relatedness effect, is observed on a concurrent lexical
      decision task. The semantic relatedness effect refers to slowed response times
      when subjects make a lexical decision to a probe that is associatively related to
      the idea they are maintaining, compared to when the probe is unrelated. The
      semantic relatedness effect occurred for semantic but not for phonological or
      visual word-form maintenance, dissipated quickly after maintenance ends, and
      survived concurrent articulatory suppression. The effect disappeared when
      subjects performed our immediate memory task with a long-term memory strategy
      rather than with active maintenance. Experiment 6 demonstrated a parallel
      phonological relatedness effect that occurs for phonological but not semantic
      maintenance, establishing a full double dissociation between the effects of
      semantic and phonological maintenance. These findings support a distinct semantic
      maintenance capacity and provide a behavioral marker through which semantic
      working memory can be studied.

PMID- 21843024
TI  - Reflections of distraction in memory: transfer of previous distraction improves
      recall in younger and older adults.
AB  - Three studies explored whether younger and older adults' free recall performance
      can benefit from prior exposure to distraction that becomes relevant in a memory
      task. Participants initially read stories that included distracting text. Later,
      they studied a list of words for free recall, with half of the list consisting of
      previously distracting words. When the memory task was indirect in its use of
      distraction (Study 1), only older adults showed transfer, with better recall of
      previously distracting compared with new words, which increased their recall to
      match that of younger adults. However, younger adults showed transfer when cued
      about the relevance of previous distraction both before studying the words (Study
      2) and before recalling the words (Study 3) in the memory test. Results suggest
      that both younger and older adults encode distraction, but younger adults require
      explicit cueing to use their knowledge of distraction. In contrast, older adults
      transfer knowledge of distraction in both explicitly cued and indirect memory
      tasks. Results are discussed in terms of age differences in inhibition and source
      constrained retrieval.

PMID- 21843025
TI  - Aging and retrospective revaluation of causal learning.
AB  - In a 2-stage causal learning task, young and older participants first learned
      which foods presented in compound were followed by an allergic reaction (e.g.,
      STEAK-BEANS-> REACTION) and then the causal efficacy of 1 food from these
      compounds was revalued (e.g., BEANS-> NO REACTION). In Experiment 1, unrelated
      food pairs were used, and although there were no age differences in compound- or
      single-cue-outcome learning, older adults did not retrospectively revalue the
      causal efficacy of the absent target cues (e.g., STEAK). However, they had weaker
      within-compound associations for the unrelated foods, and this may have prevented
      them from retrieving the representations of these cues. In Experiment 2, older
      adults still showed no retrospective revaluation of absent cues even though
      compound food cues with pre-existing associations were used (e.g., STEAK-POTATO),
      and they received additional learning trials. Finally, in Experiment 3, older
      adults revalued the causal efficacy of the target cues when small, unobtrusive
      icons of these cues were present during single-cue revaluation. These findings
      suggest that age-related deficits in causal learning for absent cues are due to
      ineffective associative binding and reactivation processes.

PMID- 21843026
TI  - Application of geographic information systems to the analysis of private dental
      practices distribution in Western Australia.
AB  - INTRODUCTION: Western Australia (WA), Australia's largest state, consists of
      approximately one-third of the country's landmass and has a population of
      approximately 2 million people. However, over 85% of this population live in a
      handful of urban centres with the majority (1.6 million) living in the state
      capital, Perth. Healthcare provision in this complex environment is difficult and
      a clear understanding of the distribution of the population and health service
      suppliers is critical to understanding and addressing the problem. The vast
      majority (80% or more) of oral health care in WA is provided by private
      practitioners on a fee-for-service basis. Although previous studies have examined
      the macro-level distribution of dentists, this study utilized a high acuity
      examination to examine the distribution of private dental practices in WA,
      especially in rural and remote areas. METHODS: Dental practice locations were
      collected from open access sources and geo-coded. Population data were obtained
      from the Australian Bureau of Statistics and divided by census districts. The
      Index of Relative Socio-Economic Disadvantage (IRSD) was aggregated to census
      district level. Population and socio-economic data were then geo-coded using
      ArcGIS v9 (ESRI; Redlands, CA, USA). With Perth primary post office used as a
      central datum point, a sequence of maps at differing magnification was overlayed
      with a grid of latitude and longitude lines, or graticules. RESULTS: Of the 602
      dental practices mapped, 75% were within 32 km of the Perth General Post Office,
      and 95% were within 256 km. In metropolitan Perth, fewer dental practices were
      located in areas that have residents of lower socioeconomic status and the
      density of distribution of these practices was greatest in the inner city region.
      CONCLUSION: This study highlights the complex nature of providing care to
      irregularly distributed populations in economic environments that are driven by
      factors not purely related to disease burden.

PMID- 21843027
TI  - The effect of dentin desensitizer on shear bond strength of conventional and self
      adhesive resin luting cements after aging.
AB  - This study tested the impact of Gluma Desensitizer on the shear bond strength
      (SBS) of two conventional (RelyX ARC, Panavia 21) and two self-adhesive (RelyX
      Unicem, G-Cem) resin luting cements after water storage and thermocycling. Human
      third molars (N=880) were embedded in acrylic resin. The buccal dentin was
      exposed. Teeth were randomly divided into four main groups, and the following
      cements were adhered: 1) RelyX ARC, 2) Panavia 21, 3) RelyX Unicem, and 4) G-Cem.
      In half of the teeth in each group, dentin was treated with Gluma Desensitizer.
      In the conventional cement groups, the corresponding etchant and adhesive systems
      were applied. SBS of the cements was tested after 1 hour (initial); at 1, 4, 9,
      16, and 25 days of water storage; and at 1, 4, 9, 16, and 25 days of
      thermocycling. SBS data were analyzed by one-way analysis of variance (ANOVA);
      this was followed by the post hoc Scheffe test and a t-test. Overall, the highest
      mean SBS (MPa) was obtained by RelyX ARC (ranging from 14.6 +/- 3.9 to 17.6 +/-
      5.2) and the lowest by Panavia 21 in combination with Gluma Desensitizer (ranging
      from 0.0 to 2.9 +/- 1.0). All tested groups with and without desensitizer showed
      no significant decrease after aging conditions compared with baseline values
      (p>0.05). Only the Panavia 21/Gluma Desensitizer combination showed a significant
      decrease after 4 days of thermocyling compared with initial values and 1 day
      thermocycling. Self-adhesive cements with Gluma Desensitizer showed increased SBS
      after aging conditions (ranging from 7.4 +/- 1.4 to 15.2 +/- 3) compared with
      groups without desensitizer (ranging from 2.6 +/- 1.2 to 8.8 +/- 2.9). No
      cohesive failures in dentin were observed in any of the test groups. Although
      self-adhesive cements with and without desensitizer presented mainly adhesive
      failures after water storage (95.8%) and thermocyling (100%), conventional cement
      (RelyX ARC) showed mainly mixed failures (90.8% and 89.2%, after water storage
      and thermocyling, respectively). Application of the Gluma Desensitizer to dentin
      before cementation had a positive effect on the SBS of self-adhesive cements.

PMID- 21843028
TI  - Microhardness of composite materials with different organic phases in deep class
      II cavities: an in vitro study.
AB  - OBJECTIVE: This study compared the microhardness of three composite resins with
      different organic matrices in deep class II cavities. MATERIALS AND METHOD: A
      total of 36 extracted molars were randomly assigned to six groups and
      standardized class II cavities were prepared. The cavity design comprised three
      steps in a mesiodistal direction with an increasing depth (2, 4, and 6 mm).
      Twelve cavities each were restored using Filtek Supreme (FS), Quixfil (QF), and
      Filtek Silorane (SI). The materials were applied in incremental layers of 2 mm
      and cured either with Halogen Translux Energy (HTE) (n=18) or LED Bluephase C8
      (LED) (n=18). Subsequently, the specimens were cross-sectioned, and microhardness
      was determined in various depths and at two different distances from the matrix.
      RESULTS: QF yielded the highest KHN microhardness values (92.67 +/- 12.77),
      followed by FS (65.53 +/- 19.52) and SI (57.67 +/- 8.33). Composites cured with
      LED achieved higher KHN values. All materials showed the highest microhardness
      values within the superficial increments and at a distance of 1000 MUm from the
      matrix.

PMID- 21843029
TI  - Caregiver attitudes to gynaecological health of women with intellectual
      disability.
AB  - BACKGROUND: There is little information available related to the reproductive
      health of people with intellectual disability (ID). The aims of the present study
      are to describe caregiver attitudes and to examine determinants of gynaecological
      health for women with ID. METHOD: We recruited 1152 caregivers (response
      rate=71.87%) and analysed their responses to a mailed-out, self-administered,
      structured questionnaire. We divided attitudinal perceptions of reproductive
      health into 4 domains: menstruation, menopause, sex education, and preventive
      healthcare. Each domain in turn had 5 issues (questions), with scores of 1 to 4
      given according to the level of agreement with each issue (low to high score:
      strongly disagree, disagree, agree, and strongly agree). The total sum score for
      each domain was 5-20 (total score range: 20-80). RESULTS: The respondents'
      attitudinal mean score was 57.78+/-4.64 (range: 48-75). The multiple logistic
      regression model revealed that the factors of "workplace training in reproductive
      health" (OR=1.793, 95% CI=1.31-2.46), "felt satisfied with public reproductive
      health services for the client" (OR=0.694, 95% CI=0.53-0.92), and "scores of
      reproductive health knowledge" (OR=1.735, 95% CI=1.29-2.34) were significantly
      correlated with attitudinal score level toward gynaecological health for women
      with ID. CONCLUSIONS: The study highlights that service authorities should
      address health policy initiatives to continue providing workplace training in
      reproductive health, public reproductive health services. There is also a need
      for caregivers to increase their knowledge of reproductive health.

PMID- 21843031
TI  - Disconnected expectations: staff, family, and supported employee perspectives
      about retirement.
AB  - BACKGROUND: Australia has few policies to support the transition of older people
      with intellectual disability from employment to retirement. This study aimed to
      identify the possibilities and barriers to retirement for older employees in
      supported employment services. METHOD: Five distinct participant groups discussed
      retirement in 6 separate focus group interviews: staff from disability
      accommodation (7) and employment services (7), members of mainstream activity
      programs for older people (4), family members (5), and supported employees (2
      groups of 6 people). RESULTS: Participants perceived retirement as a risk to the
      well-being and participation of employees. Participants were pessimistic about
      the availability of necessary support in retirement. The need for additional
      resources and skills was identified, but the utility of inclusion strategies was
      not recognised. Continued segregation through specialist programs or adaptation
      of existing employment programs was the most commonly suggested retirement option
      by staff and family members. CONCLUSION: Perceptions did not reflect the current
      policy imperatives of social participation. This poses an additional obstacle to
      conceptualising, planning, and supporting quality of life for older people with
      intellectual disability.

PMID- 21843030
TI  - Transforming staff practice through active support.
AB  - BACKGROUND: Active support is being introduced in many residential and respite
      homes in an effort to improve engagement in meaningful activity of people with
      intellectual disability. METHOD: A train-the-trainer approach was used in a large
      government organisation that supports people with intellectual disability in
      Australia. Five apprentice trainers were trained to provide active support
      training to 65 staff associated with 6 group homes. These 5 trainers were then
      monitored to provide training to 54 staff in another 6 group homes. Staff
      evaluated their interactive training experiences, and pre and post outcome data
      were collected for a small number of service users from the second set of group
      homes, along with staff outcome data regarding residential working practices,
      group home management, and staffing practices. RESULTS: The train-the-trainer
      model proved to be an effective strategy for training large numbers of staff. The
      interactive training component was particularly effective and was associated with
      improvements in service user engagement in domestic tasks and decreased
      depression levels. Staff job satisfaction increased and significant improvements
      were recorded in residential working practices. CONCLUSIONS: Active support
      training is an effective strategy for empowering staff to better support people
      with an intellectual disability to be meaningfully engaged in daily activities.
      There are implications for organisations related to ongoing implementation and
      practice improvement.

PMID- 21843032
TI  - Avoiding institutional outcomes for older adults living with disability: the use
      of community-based aged care supports.
AB  - BACKGROUND: Most people with a disability want to remain living in their own home
      as they age. Without additional support, people with a disability may not be able
      to avoid moving into residential aged care, attending day programs, or becoming
      isolated from participation in the wider community. This study examined whether
      participants perceived access to community-based aged care supports assisted with
      avoiding receiving more institutional models of service as they age. METHOD:
      Qualitative research processes were used to explore the perceptions of 60
      individuals with a disability aged 50 years and over, in relation to ageing and
      the value of community-based aged care. RESULTS: Findings indicated that
      participants receiving community-based aged care supports reported benefits
      including opportunities to develop relationships, maintain daily living skills
      and participate in community activities. CONCLUSION: Due to a lack of confidence
      in the availability of access to mainstream community-based aged care services,
      many participants felt vulnerable or unsure about their future and ability to
      remain living in their own home. Several participants commented that this meant
      that an undesired early relocation into residential aged care or congregate
      disability services appeared inevitable.

PMID- 21843033
TI  - The development of vocabulary in Spanish children with Down syndrome:
      comprehension, production, and gestures.
AB  - BACKGROUND: Our main purpose was to compare the lexical development of Spanish
      children with Down syndrome (DS) and children with typical development (TD) to
      investigate the relationship between cognitive and vocabulary development in
      comprehension and oral and gestural production. METHOD: Participants were 186
      children with DS and 186 children with TD, with a mental age (MA) of 8-29 months
      and matched on gender and MA. Information about vocabulary was obtained using a
      new Spanish adaptation of the MacArthur-Bates CDI for children with DS. RESULTS:
      No significant differences in oral production were found. Lexical comprehension
      and gestural production of children with DS were superior. Similar to children
      with TD, gestural production in children with DS decreased as oral production
      increased. CONCLUSION: Our study provides evidence to support that lexical
      comprehension and gesture production are strengths in children with DS. With
      respect to oral production, our results do not support a specific dissociation
      between cognitive and lexical development.

PMID- 21843034
TI  - An initial evaluation of a long-term, sustainable, integrated community-based
      physical activity program for adults with intellectual disability.
AB  - BACKGROUND: Physical activity (PA) programs for adults with intellectual
      disability (ID) have positive impacts, at least in the short term. No research
      has been reported on the effect of long-term engagement in PA programs for adults
      with ID. This paper explores the physical and psychosocial benefits gained by two
      individuals with mild ID who participated in a long-term PA program. METHOD:
      Accelerometery was used to collect PA data during the program and for 7-day
      periods outside of the program. To explore the psychosocial outcomes gained from
      participating in the program, participants and their caregivers were interviewed
      about their participation experiences. RESULTS: Across time, a decrease in the
      amount of light activity engaged in during sessions was found, with participants
      gradually increasing their moderate to vigorous activity. Psychosocial benefits,
      including meeting new people and gaining social acknowledgement were reported by
      participants and caregivers. CONCLUSIONS: Long-term, sustainable, low cost PA
      programs (such as the one under investigation) can minimise barriers to physical
      activity for people with ID.

PMID- 21843037
TI  - Immunogenicity of two oat varieties, in relation to their safety for celiac
      patients.
AB  - OBJECTIVE: Most of the recent studies suggest that oats are well tolerated by
      celiac disease (CD) patients. However, it is still possible that different oat
      cultivars may display different biological properties relevant for CD
      pathogenesis. We aimed to investigate biological and immunological properties of
      two oat varieties, Avena genziana and Avena potenza, in relation to their safety
      for CD patients. MATERIAL AND METHODS: Phosphorylation of extracellular signal
      regulated kinase (ERK) and trans-epithelial electrical resistance (TEER) were
      evaluated in CaCo-2 cells treated with peptic-tryptic (PT) digests from the two
      oats and from gliadin (PTG). With the same PT-digests, duodenal biopsies from 22
      CD patients were treated in vitro for 24 h and density of CD25+ cells in lamina
      propria and of intraepithelial CD3+ T cells was measured, as well as crypt cell
      proliferation and epithelial expression of interleukin 15. Finally, interferon
      gamma (IFN-gamma) production was measured as evidence of gliadin-specific T-cell
      activation by PT-digests. RESULTS: In contrast to PTG, oats PT-digests were not
      able to induce significant increase in ERK phosphorylation and decrease in TEER
      in CaCo-2 cells. In the organ culture system, oats PT-digests, unlike PTG, did
      not induce significant increase in crypt enterocyte proliferation, increase in
      interleukin 15 expression or in lamina propria CD25+ cells. Nevertheless Avena
      potenza increased intraepithelial T-cell density, while Avena genziana-induced
      IFN-gamma production in 3/8 CD intestinal T cell lines. CONCLUSIONS: Our data
      show that Avena genziana and Avena potenza do not display in vitro activities
      related to CD pathogenesis. Some T-cell reactivity could be below the threshold
      for clinical relevance.

PMID- 21843038
TI  - Evaluation of root resorption following rapid maxillary expansion using cone-beam
      computed tomography.
AB  - OBJECTIVE: To evaluate the root resorption after rapid maxillary expansion (RME)
      via cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Records of 25
      patients who had undergone RME with tooth-borne banded expander were obtained
      from the archive of the orthodontic department. CBCT data were reconstructed with
      surface and volume rendering, and the volumetric images were manipulated to
      display the root surfaces from various orientations. On these three-dimensional
      images, permanent first molars and first and second premolars were segmented, and
      their roots were isolated. Volumes of roots were calculated. The difference
      between pre-expansion and postexpansion root volumes was statistically evaluated
      with a paired-samples t-test. Also, the percentage of root volume loss was
      calculated for each root and statistically compared with each other with one-way
      analysis of variance at the P < .05 level. RESULTS: The difference between the
      pre-expansion and postexpansion root volumes was statistically significant for
      all roots investigated. Maximum volume decrease was observed for the mesiobuccal
      root of first molar teeth (18.60 mm(3)). It was determined that the distobuccal
      root of first molar teeth was less affected from the expansion procedure (9.47
      mm(3)). No statistically significant difference was found for the percentage of
      root volume loss. CONCLUSION: Following RME treatment, significant root volume
      loss was observed for all investigated posterior teeth. However, the percentage
      of volume loss was not statistically different among roots.

PMID- 21843039
TI  - Emergency colectomy for fulminant Clostridium difficile colitis: Striking the
      right balance.
AB  - The number of reported cases of Clostridium difficile (CD) infections has
      increased markedly worldwide. CD causes a spectrum of clinical syndromes, ranging
      from mild diarrhea to a very severe illness in the form of pseudomembranous
      colitis (PMC), toxic megacolon, leading to colonic perforation, peritonitis, and
      even death. In today's practice, toxic megacolon is more often caused by
      pseudomembranous colitis than ulcerative colitis. There is urgent need to
      establish clear guidelines about how and when to refer patients with fulminant CD
      colitis to surgeons. Furthermore, there is no strict protocol for the timing of
      surgical intervention. The aim of this review is to review the available evidence
      about the criteria for referral to surgeons and timing for surgery. Medline
      search was carried out for articles published on fulminant CD colitis with
      emergency colectomy from 1966 to 2010. There were no prospective randomized
      trails. All retrospective cohort and case control studies were included. We
      excluded case reports, letters, and studies with less than five patients. Our
      search showed that patients with confirmed or suspected CD who failed to respond
      to maximum medical therapy and develop three of the following should be referral
      for surgical assessment: abdominal pain, abdominal distension, localized
      tenderness, pyrexia >38 degrees C, and tachycardia >100 beats per minute. In
      addition to the above, if the patient is above 65 years old and develops four of
      the following, they should be considered for an emergency colectomy: WBC >16 *
      109/l, lactate >2.2 mmol/l, albumin <30 g/l, blood pressure <90 mm Hg,
      CT/endoscopy evidence of severe colitis in spite of maximum anti-clostridial
      therapy. Colectomy still carries a high mortality rate; however, timely surgical
      intervention in fulminant CD colitis (FCDC) prevents many deaths in selected
      cases. In the absence of published prospective multicenter trial, we suggest that
      our criteria may enhance early diagnosis and consideration of early referral for
      surgery. Ultimately, this may reduce the significant morbidity and mortality
      associated with FCDC.

PMID- 21843040
TI  - Vitreous amyloidosis in two large mainland Chinese kindreds resulting from
      transthyretin variant Lys35Thr and Leu55Arg.
AB  - OBJECTIVE: To describe the clinical and pathological findings of two large
      mainland Chinese kindreds with vitreous amyloidosis and associated transthyretin
      mutation. METHODS: Twenty individuals from two kindreds with vitreous amyloidosis
      were ascertained. The transtheretin (TTR) gene of each individual was analyzed,
      and a clinical examination was obtained on the index patient. RESULTS: Vitreous
      amyloidosis and radiculopathy were the significant findings in affected
      individuals. Vitrectomy was performed on the severely affected individuals, with
      resulting postoperative visual acuity of 20/80 to 20/25. Congo red staining
      demonstrated amyloid in the vitreous specimen. In Case A, DNA sequencing of exon
      2 in the TTR gene revealed a base-pair substitution at codon 35, AAG > ACG
      (Lys35Thr). In Case B, a missense mutation of leucine-to-arginine substitution
      was identified at amino acid position 55 in exon 3, CTG > CGG (Leu55Arg).
      CONCLUSIONS: TTR Lys35Thr and Leu55Arg mutations are associated with vitreous
      amyloidosis. The phenotype is variable, with vitreous opacities occurring
      earlier, and sometimes as the sole signs of amyloidotic polyneuropathies (FAPs).
      Vitrectomy improves vision in some patients with vitreous amyloidosis.

PMID- 21843041
TI  - Five-year progression-free survival in 577 patients operated on with laparoscopic
      radical prostatectomy for localized prostate cancer.
AB  - OBJECTIVE: Laparoscopic radical prostatectomy (LRP) was introduced in the
      Department of Urology, Oslo University Hospital, in 2002. The aim of this study
      was to report mid-term oncology results and survival data. MATERIAL AND METHODS:
      From February 2002 to November 2007, 582 consecutive patients with localized
      prostate cancer underwent LRP. Data were collected prospectively into a database.
      RESULTS: Mean and median follow-up after LRP was 30.3 months (+/- 15.5) and 36.0
      months (range 3-72). Five patients (1%) were lost during follow-up. Two patients
      died of prostate cancer during the study period and 10 patients died of other
      causes. The overall positive surgical margin (PSM) rate was 29% and decreased to
      13% for the last 100 patients. The overall PSA progression-free survival (PFS)
      was 85% at 3 years and 73% at 5 years. Gleason score in the tumour specimen, pT
      stage and surgical margins were statistical significant independent predictors of
      biochemical PFS. CONCLUSION: These oncology results and 5-year PFS data after LRP
      are in line with other reports.

PMID- 21843042
TI  - The inter-relation between epithelial cells of Malassez and vessels studied
      immunohistochemically in the periodontal membrane of human primary and permanent
      teeth.
AB  - BACKGROUND: Only few immunohistochemical studies have focused on the periodontal
      membrane in human primary teeth. Recently, studies on epithelial cells of
      Malassez and innervation have been published. Studies on the inter-relation
      between vessels and the epithelial cells of Malassez are seemingly lacking. AIM:
      he aim of this immunohistochemical study is to describe the histological inter
      relation between epithelial cells of Malassez and vessels in the periodontal
      membrane close to the root surface of human primary and permanent teeth. METHODS:
      Twenty-nine human primary teeth and 15 permanent teeth were extracted in
      connection with dental treatment. The teeth were fixated, embedded in paraffin,
      cut in serial sections and examined immunohistochemically for epithelial cells of
      Malassez using wide spectrum screening and vessels using Von Willebrand Factor
      VIII. RESULTS: The study showed that vessels and epithelial cells of Malassez are
      seen parallel to the root surface. The vessels are seen on that side of the
      epithelial cells of Malassez, which are not facing the root surface. CONCLUSION:
      The vascularization appeared similar in primary and permanent teeth.

PMID- 21843044
TI  - A non-paternalistic value theory of occupational therapy: a comment to Dige.
AB  - In an article by Morten Dige in the Scandinavian Journal of Occupational Therapy,
      a value theory for occupational therapy is developed where the goals of
      occupational therapy, i.e. activity and participation, are seen as valuable in
      themselves. Such a value theory opens up for a paternalistic approach towards the
      person in need of occupational therapy who risks being excluded from certain
      types of activities and the theory even risks excluding certain groups of
      persons. In this comment to Dige, it is argued that adopting a more subjective
      approach to value, in which activity and participation are instrumental to values
      such as subjective well-being or the fulfilment of desires, the risk of inherent
      paternalism and exclusion is minimized. Moreover, activity and participation can
      still maintain their central role as goals of occupational therapy.

PMID- 21843045
TI  - Working memory training for patients with acquired brain injury: effects in daily
      life.
AB  - OBJECTIVE: Working memory deficits are common after brain injury and cause
      multiple problems for patients in daily life. Research has shown that it is
      possible to improve working memory functioning by training. The aim of this study
      was to examine whether patients with moderate to severe cognitive deficits after
      brain injury could profit from working memory training and if that training had
      any impact on their daily life activities. A training programme was designed
      consisting of computerized training software (Cogmed QM), coaching, education,
      and peer support. The design was a prospective cohort study in a naturalistic
      setting at an outpatient centre for persons with acquired brain injury. METHODS:
      Participants were 18 patients, aged 17-64, who had difficulties in daily life
      pertaining to working memory deficits. Data were collected pre- and post-training
      and at a six-month follow-up. RESULTS: Despite relatively severe cognitive
      deficits patients were able to carry out a demanding training programme with
      positive results. The computerized training showed a significant improvement on
      trained working memory tasks. Patients starting at a low training level improved
      the most. Self-rating measurements and interviews indicated that patients
      experienced fewer cognitive problems in daily life after training. The effect was
      maintained at the six month follow-up. Training results were not affected by age
      or time post-injury (1-22 years).

PMID- 21843046
TI  - Nephrogenic adenoma of the bladder in a prune belly syndrome patient: case report
      and review of the literature.
AB  - Nephrogenic adenoma (NA) is a rare lesion of the urinary tract widely considered
      to be a metaplastic response to urothelial injury. Herein, we present the case of
      an 8-year-old male with prune belly syndrome who presented with gross hematuria.
      Investigation revealed a bladder mass; however, upon cystoscopic examination,
      multiple polypoid lesions were identified. Microscopic examination revealed NA of
      the bladder. To our knowledge, this is the second reported case of NA of the
      bladder in association with prune belly syndrome.

PMID- 21843048
TI  - Abnormal histone acetylation and methylation levels in esophageal squamous cell
      carcinomas.
AB  - To investigate whether alterations in histone modifications occur in esophageal
      squamous cell carcinoma (ESCC), we measured histone H3/ H4 acetylation and
      H3K4/H3K27 methylation levels, as well as the expression of chromatin modifier
      genes in tumor and healthy esophageal tissue from ESCC patients. We found
      evidence of global H3 and H4 hypoacetylation, H3K4 and H3K27 hypermethylation in
      ESCC tissue. Both H3 hypoacetylation and H3K27 hypermethylation correlated with
      the severity and histological differentiation of the tumor, and H3K4
      hypermethylation also correlated with tumor differentiation. Our results suggest
      that aberrant histone modifications may play an important role in the development
      and progression of ESCC.

PMID- 21843047
TI  - Polymorphisms in interleukin-6-6331 influences the susceptibility of a Chinese
      population to gastric cancer.
AB  - We investigated the association of Interleukin (IL)-6-6331 polymorphisms with
      susceptibility to gastric cancer in 375 patients with gastric cancer and 386 age-
      and gender-matched healthy controls. After adjustment for the potential
      confounding effects of gender and age, IL-6-6331TC genotype was associated with a
      decreased risk of gastric cancer compared with the CC genotype. Further
      stratification analyses indicated that the protective effect of TC genotype was
      also observed in poorly differentiated gastric cancer, noncardia gastric cancer,
      and intestinal-type gastric cancer, respectively. These results suggest that the
      IL-6-6331 polymorphism is involved in susceptibility to developing gastric
      cancer.

PMID- 21843049
TI  - Two-year clinical experience with tomotherapy: the French national cancer
      institute project on implementing new technology.
AB  - The pooled 2-year clinical experience using three tomotherapy units installed in
      France in 2007 is presented. Treatment indications and protocols were devised for
      each disease site and were the result of a consensus. A total of 642 patients
      were treated for central nervous system, head and neck, thoracic, abdominal, and
      pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and
      0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5
      chronic toxicity. The use of tomotherapy in a broad clinical practice is safe,
      and acute and chronic toxicity both are acceptable for all anatomical locations.

PMID- 21843050
TI  - IGF1R-targeted therapy and its enhancement of doxorubicin chemosensitivity in
      human osteosarcoma cell lines.
AB  - Type-I insulin-like growth factor receptor (IGF1R) and its signaling play an
      important role in osteosarcomagenesis, tumor progression, and chemoresistance.
      The purpose of this study was to investigate both the effect and mechanisms of
      IGF1R inhibition by tyrphostin AG1024 in the presence or absence of doxorubicin
      in a panel of six osteosarcoma cell lines and a self-established doxorubicin
      resistant cell line. We are the first to indicate that targeting IGF1R together
      with doxorubicin achieved additive anti-osteosarcoma growth effect, accompanied
      with increased apoptosis, cytotoxicity, and dual cell cycle arrests. In
      conclusion, IGF1R inhibition can enhance doxorubicin chemotherapy in some
      osteosarcoma cell lines.

PMID- 21843051
TI  - New perspectives on zoledronic acid in breast cancer: potential augmentation of
      anticancer immune response.
AB  - A small subset of T cells (gamma-delta T cells) is able to recognize
      phosphoantigens that are overexpressed in some cancer cells and may selectively
      target and kill cancer cells with high levels of phosphoantigen. Moreover,
      nitrogen-containing bisphosphonates, such as zoledronic acid, are able to induce
      accumulation of specific phosphoantigens in some cancer cells. A recent
      preclinical study showed that gamma-delta T cells effectively targeted and killed
      zoledronic acid-treated estrogen-receptor-positive breast cancer cells. These new
      data provide growing insight into a potential mechanism of action for some of the
      anticancer activity demonstrated by zoledronic acid in breast cancer clinical
      trials.

PMID- 21843053
TI  - Post-operative subcutaneous fat necrosis in a newborn: a case report.
AB  - Subcutaneous fat necrosis of the newborn (ScFN) is an uncommon condition of
      neonates and infants. The disorder is caused by generalized and local tissue
      hypoperfusion. The ScFN tends to improve spontaneously with or without some
      severe complications such as hypercalcemia. The ScFN may occur as iatrogenic
      after hypothermic surgical interventions. We present iatrogenic ScFN in a newborn
      with uncomplicated hypercalcemia due to cold exposure on operating table during
      at an umbilical cord hernia operation. To our knowledge, this is the first report
      of a patient in whom ScFN occurred during a commonly performed and relatively
      short-term "nonhypothermic" operation.

PMID- 21843052
TI  - Recombinant modified vaccinia virus ankara (MVA) expressing wild-type human p53
      induces specific antitumor CTL expansion.
AB  - The p53 gene product is an attractive target for tumor immunotherapy. The present
      study aims to understand the potential of MVAp53 vaccine to induce expansion of
      p53-specific cytotoxic T lymphocyte ex vivo in cancer patients. The result
      indicated that 14 of 23 cancer patients demonstrated p53-specific IFN-gamma
      production, degranulation, cell proliferation, and lysis of p53 overexpressed
      human tumor cell lines. These experiments show that MVAp53 stimulation has the
      potential to induce the expansion of p53-specific cytotoxic T lymphocyte from the
      memory T cell repertoire. The data suggest that MVAp53 vaccine is an ideal
      candidate for cancer immunotherapy.

PMID- 21843054
TI  - Intrauterine fetal death due to cardiac rhabdomyomas.
AB  - A 21-year-old patient, in her first and regularly controlled uneventful
      pregnancy, was admitted to hospital due to lower leg edema, hypertension,
      proteinuria, and weight gain. Fetal death occurred the next day and a female
      nonhydropic fetus, 40 cm CH, 1460 grams, at 29-week gestation was delivered. An
      autopsy showed no visible gross abnormalities except in the heart. The heart was
      enlarged, with five intramural and subendocardial nodules, 0.3 to 1 cm in size,
      three in the left ventricular free wall, and one in the right ventricle and right
      atrium, sharply demarcated, reddish-gray, moderately firm, with the typical
      appearance of rhabdomyoma.

PMID- 21843055
TI  - Cardiac myxoma with glandular differentiation: an immunohistochemical and
      ultrastructural study.
AB  - A case of cardiac myxoma with glandular differentiation is reported. The patient
      did not have elements of the Carney triad or syndrome. The tumor was mainly
      composed of characteristic stellate cells in a focally collagenized, myxoid
      stroma, along with aggregates of glandular-forming epithelial cells, with mucin
      containing intra- and intercellular lumina. Ultrastructurally, these gland spaces
      displayed short, straight microvilli and junctional complexes. The epithelial
      cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin
      was positive in the stellate cells and negative in the epithelial component. The
      potential origin from pluripotent mesenchymal cells or from seeded stem cells is
      hypothesized for glandular differentiation in myxomas. Further studies are
      required to unravel the relationship between stellate cells and the diverse
      heterologous components reported in these tumors.

PMID- 21843056
TI  - Ultrastructural features of human atherosclerosis.
AB  - Healthy human arteries are composed of three layers: the intima, the media, and
      the adventitia. Endothelial cells, which form the tunica intima, provide the
      physical interface between blood and surrounding tissue, regulate nutrient and
      blood component traffic, and participate in many physiologic events, such as
      hemostasis, inflammation, and angiogenesis. Within the tunica media, smooth
      muscle cells and extracellular matrix proteins, such as elastin, collagen, and
      proteoglycans, are quantitatively the largest components of the aortic vascular
      wall. The structural changes with atherosclerosis are currently considered
      degenerative phenomena, which primarily involve a sequence of reactions within
      the intima and include monocyte recruitment and macrophage formation, lipid
      deposition, smooth muscle cell migration, proliferation, and extracellular matrix
      synthesis. The molecular and cellular mechanisms underlying the disease cascade
      have been thoroughly investigated in experimental animals and cell culture, but
      the question of how these models can correctly mimic the human course of the
      disease remains open to debate. In the present review the basic structure of
      healthy human arteries and the pathological events occurring during the
      atherosclerotic process have been examined by both transmission and scanning
      electron microscopy. Human atherosclerotic lesions are presented and described in
      the following order: initial lesions, fatty dots and streaks, intermediate
      lesions, atheroma and fibrofatty plaques, and complicated lesions.

PMID- 21843057
TI  - Sensory innervation of the female human umbilical skin: morphological studies.
AB  - BACKGROUND: Sensory stimuli are conducted by several cutaneous sensory nerves and
      tactile corpuscles. The latter are specialized sensory organs that represent the
      starting point of many afferent sensory pathways. To date, our knowledge about
      the distribution of the sensory innervation in the umbilical skin of females is
      incomplete. AIM OF THE STUDY: To elucidate the morphology of the cutaneous
      innervation of the normal female umbilical skin. MATERIALS AND METHODS: Biopsies
      of normal umbilical skin were obtained from female patients undergoing umbilical
      hernial repair. The specimens were processed for both immunohistological
      (antibodies against PGP9.5, pan-neuronal marker, and S-100 protein, marker of
      Schwann cells) and ultrastructural (transmission electron microscopy)
      examinations. RESULTS: The authors found abundant genital end-bulb-like
      structures, numerous epidermal and dermal Merkel cells, Meissner and Ruffini
      corpuscles, intraepidermal nerve terminals, and multiple free nerve endings
      surrounding the ducts and acini of the sweat glands. CONCLUSIONS: The umbilical
      skin of females has abundant sensory innervation similar to that of the glans
      penis.

PMID- 21843058
TI  - Meckel syndrome with Caroli disease and choledochal cysts.
AB  - Meckel syndrome is a lethal autosomal recessive disorder characterized by the
      triad of cystic renal dysplasia, occipital encephalocele, or other anomaly of the
      central nervous system and post-axial polydactyly. Malformation of the ductal
      plate is an integral component of Meckel syndrome. Ductal plate malformations
      include congenital hepatic fibrosis, biliary hamartoma, autosomal dominant
      polycystic liver disease, Caroli disease, and choledochal cyst. The occurrence of
      cystic hepatic disease, Caroli disease, and choledochal cyst have not been
      highlighted. This is a report of a 26-week fetus with features of Meckel
      syndrome, Caroli disease, and choledochal cyst.

PMID- 21843059
TI  - Bevacizumab pharmacogenetics in tumor treatment: still looking for the right
      pieces of the puzzle.

PMID- 21843060
TI  - Pharmacogenomics for tailoring cardiovascular and anticancer drugs: from
      genotyping to whole-genome sequencing.

PMID- 21843062
TI  - Pharmacogenomics, biochemistry, toxicology, microbiology and cancer research in
      one go.
AB  - Arylamine N-acetyltransferases (NATs) are phase II xenobiotic metabolizing
      enzymes playing a key role in the detoxification and metabolic activation of
      aromatic amine xenobiotics. The triennial International NAT Workshop has been an
      important academic meeting where developments in the study of NATs and aromatic
      amine metabolism have been presented. The 2010 Workshop took place in University
      Paris Diderot Paris, France. Topics included: structures and functions of
      eukaryotic and prokaryotic NATs, gene regulation and expression of human NATs,
      polymorphisms and their effects, arylamine metabolism and toxicity. Nomenclature
      issues were also discussed.

PMID- 21843063
TI  - A hub for bench-to-bedside pharmacogenomic-based research.
AB  - In 2003 Duke University (Durham, NC, USA) launched the Institute for Genome
      Sciences & Policy (IGSP) as an interdisciplinary network of centers comprised of
      scientists, engineers and physicians, as well as experts in law, business,
      economics public policy and ethics. Within this environment, the IGSP and its
      Center for Genomic Medicine form the hub for pharmacogenomic research discovery
      initiatives through collaborations with other scientific and clinical units at
      the Duke University Medical Center. The Center for Genomic Medicine specifically
      focuses on developing strategies for translating and implementing pharmacogenomic
      discoveries into the clinical arena; therefore, by harnessing the resources of
      the IGSP as well as other complementary centers on campus, Duke University is
      poised to accelerate the development of novel pharmacgenomic paradigms for the
      prevention and treatment of disease. These new treatment paradigms can,
      potentially, ensure that the right dose of the right drug is prescribed to the
      right individual - an often stated goal of personalized medicine and
      pharmacogenomics.

PMID- 21843064
TI  - SNPs in ADAMTS13.
AB  - The multidomain metalloprotease ADAMTS13 limits thrombus formation via the
      cleavage of large multimeric forms of von Willebrand factor. Deficiency of
      functional ADAMTS13 is associated with a number of disease pathologies including
      thrombotic thrombocytopenic purpura, cardiovascular disease and inflammation. To
      date, deficiency is known to result from mutations in the ADAMTS13 gene or from
      inhibitory and non-neutralizing antibodies. The exact contributory effect of
      genetic variation in ADAMTS13 on observable pathology is unclear, and
      specifically, polymorphisms of ADAMTS13 have not been the focus of much
      systematic study. Here we have amassed an up-to-date collection of ADAMTS13
      polymorphisms described in the literature and from the National Center for
      Biotechnology Information's SNP database. This article considers the effect that
      these polymorphisms may have on the expression and function of ADAMTS13 and
      speculates on their relevance in future therapies based on pharmacogenomics.

PMID- 21843065
TI  - Pharmacogenomics of oral antidiabetic medications: current data and
      pharmacoepigenomic perspective.
AB  - Type 2 diabetes mellitus (T2DM) is an increasingly prevalent disease. Several
      classes of drugs are currently available to treat T2DM patients; however,
      clinical response to these drugs often exhibits significant variation among
      individuals. For the oral antidiabetic drug classes of sulfonylureas,
      nonsulfonylurea insulin secretagogs, biguanides and thiazolidinediones,
      pharmacogenomic evidence has accumulated demonstrating an association between
      specific gene polymorphisms and interindividual variability in their therapeutic
      and adverse reaction effects. These polymorphisms are in genes of molecules
      involved in metabolism, transport and therapeutic mechanisms of the
      aforementioned drugs. Overall, it appears that pharmacogenomics has the potential
      to improve the management of T2DM and help clinicians in the effective
      prescribing of oral antidiabetic medications. Although pharmacogenomics can
      explain some of the heterogeneity in dose requirements, response and incidence of
      adverse effects of drugs between individuals, it is now clearly understood that
      much of the diversity in drug effects cannot be solely explained by studying the
      genomic diversity. Epigenomics, the field that focuses on nongenomic
      modifications that influence gene expression, may expand the scope of
      pharmacogenomics towards optimization of drug therapy. Therefore,
      pharmacoepigenomics, the combined analysis of genetic variations and epigenetic
      modifications, holds promise for the realization of personalized medicine.
      Although pharmacoepigenomics has so far been evaluated mainly in cancer
      pharmacotherapy, studies on epigenomic modifications during T2DM development
      provide useful data on the potential of pharmacoepigenomics to elucidate the
      mechanisms underlying interindividual response to oral antidiabetic treatment. In
      summary, the present article focuses on available data from pharmacogenomic
      studies of oral antidiabetic drugs and also provides an overview of T2DM
      epigenomic research, which has the potential to boost the development of
      pharmacoepigenomics in antidiabetic treatment.

PMID- 21843066
TI  - Relationship between P-glycoprotein and second-generation antipsychotics.
AB  - The membrane transport protein P-glycoprotein (P-gp) is an interesting candidate
      for individual differences in response to antipsychotics. To present an overview
      of the current knowledge of P-gp and its interaction with second-generation
      antipsychotics (SGAs), an internet search for all relevant English original
      research articles concerning P-gp and SGAs was conducted. Several SGAs are
      substrates for P-gp in therapeutic concentrations. These include amisulpride,
      aripiprazole, olanzapine, perospirone, risperidone and paliperidone. Clozapine
      and quetiapine are not likely to be substrates of P-gp. However, most
      antipsychotics act as inhibitors of P-gp, and can therefore influence plasma and
      brain concentrations of other substrates. No information was available for
      sertindole, ziprasidone or zotepine. Research in animal models demonstrated
      significant differences in antipsychotic brain concentration and behavior owing
      to both P-gp knockout and inhibition. Results in patients are less clear, as
      several external factors have to be accounted for. Patients with polymorphisms
      which decrease P-gp functionality tend to perform better in clinical settings.
      There is some variability in the findings concerning adverse effects, and no
      definitive conclusions can be drawn at this point.

PMID- 21843067
TI  - Pharmacogenetic testing to predict antipsychotic-induced weight gain: a
      systematic review.
AB  - Weight gain is an important side effect of antipsychotic drugs. Since the high
      interindividual difference in weight gain suggests that genetic factors play a
      role in this weight gain, studies have tried to identify these factors. Most of
      these studies were carried out in the past few years and focussed largely on
      receptor polymorphisms, although some tried to explain the variation in weight
      gain by differences in pharmacokinetics. Unfortunately, the results of these
      association studies are often conflicting, which makes it hard to apply this
      genetic knowledge in daily clinical practice. This article summarizes the
      findings of these association studies and focuses on differences in study
      methodology in an attempt to explain why study results could have been
      conflicting. Furthermore, the feasibility of genetic testing in today's clinical
      practice is discussed, using a model that consists of four components; analytical
      validity, clinical validity, clinical utility and ethical, legal and social
      issues.

PMID- 21843073
TI  - Unusual presentation of congenital infantile fibrosarcoma in seven infants with
      molecular-genetic analysis.
AB  - Congenital infantile fibrosarcoma (CIFS) is a rare mesenchymal tumor that
      primarily presents in the soft tissue of the distal extremities and occasionally
      in unusual locations such as the lung and retroperitoneum. Herein, we report
      seven cases of unusual presentations of CIFS. These cases include three in the
      lungs, one in the retroperitoneum with cord compression, one in the posterior
      trunk, one in the heart, and one infratemporal involving the sphenoid bone. All
      tumors demonstrated CIFS's characteristic t(12;15)(p13;q25) and associated ETV6
      NTRK3 gene fusion. One of the three lung cases was previously reported as primary
      bronchopulmonary fibrosarcoma (PBPF), but molecular analysis of the paraffin
      embedded tissue revealed the ETV6-NTRK3 gene fusion consistent with CIFS. We show
      that CIFS may occur in unusual sites including visceral locations, and we propose
      that neoplasms displaying the ETV6-NTRK3 gene fusion represent the visceral
      components of CIFS.

PMID- 21843074
TI  - Termination of resuscitation of nontraumatic cardiopulmonary arrest: resource
      document for the National Association of EMS Physicians position statement.
AB  - In the development of an emergency medical services (EMS) system, medical
      directors should consider the implementation of protocols for the termination of
      resuscitation (TOR) of nontraumatic cardiopulmonary arrest. Such protocols have
      the potential to decrease unnecessary use of warning lights and sirens and save
      valuable public health resources. Termination-of-resuscitation protocols for
      nontraumatic cardiopulmonary arrest should be based on the determination that an
      EMS provider did not witness the arrest, there is no shockable rhythm identified,
      and there is no return of spontaneous circulation (ROSC) prior to EMS transport.
      Further research is needed to determine the need for direct medical oversight in
      TOR protocols and the duration of resuscitation prior to EMS providers'
      determining that ROSC will not be achieved. This paper is the resource document
      to the National Association of EMS Physicians position statement on the
      termination of resuscitation for nontraumatic cardiopulmonary arrest.

PMID- 21843075
TI  - Tregs in immunotherapy: opportunities and challenges.

PMID- 21843076
TI  - Tumor-reactive CD4+ T cells: plasticity beyond helper and regulatory activities.

PMID- 21843077
TI  - Therapeutic potential of targeting TNF/TNFR family members in asthma.

PMID- 21843078
TI  - DIAPREV-IT study of diabetes therapy Diamyd(r) receives further funding and will
      continue despite disappointing Phase III trial results.

PMID- 21843079
TI  - Use of ipilimumab in melanoma.

PMID- 21843080
TI  - Phacilitate Barcelona active immunotherapeutics forum. 11-13 May 2011, Barcelona,
      Spain.
AB  - The era of active immunotherapy has now been successfully ushered into the
      clinical realm of advanced prostate cancer. The successful clinical trial
      development and US FDA approval of sipuleucel-T (Provenge(r)) has revamped the
      therapeutic paradigm for advanced prostate cancer. Nonetheless, physician and
      patient education as well as regulatory pathways and manufacturing efficiencies
      are still required in order to optimize patient care. These topics were covered
      at the Phacilitate Barcelona Active Immunotherapeutics Forum.

PMID- 21843081
TI  - Development of bavituximab, a vascular targeting agent with immune-modulating
      properties, for lung cancer treatment.
AB  - Bavituximab is a chimeric monoclonal antibody directed against the membrane
      phospholipid phosphatidylserine. Phosphatidylserine exposure is increased on
      endothelial cells and apoptotic cancer cells in solid tumors, allowing tumor
      specific targeting of bavituximab. Bavituximab binding results in tumor vessel
      occlusion and enhanced antitumor immunity. Preclinical investigations have
      demonstrated efficacy as monotherapy and in combination with other modalities
      against multiple cancer types. Phase I clinical trials of bavituximab monotherapy
      and in combination with chemotherapy in adults with refractory solid tumors have
      been completed. Phase II trials of bavituximab in combination with chemotherapy
      for the first- and second-line treatment of advanced non-small-cell lung cancer
      are currently ongoing. This article summarizes the preclinical development and
      clinical experience with bavituximab in non-small-cell lung cancer.

PMID- 21843082
TI  - Tumor-associated dendritic cells: molecular mechanisms to suppress antitumor
      immunity.
AB  - Evaluation of: Watkins SK, Zhu Z, Riboldi E et al. FOXO3 programs tumor
      associated DCs to become tolerogenic in human and murine prostate cancer. J.
      Clin. Invest. 121(4), 1361-1372 (2011). Tumor-associated dendritic cells (TADCs)
      have been described as immune-suppressive cells in cancers, and part of the
      molecular mechanisms has emerged. The transcription factor FOXO3--one of the
      tumor suppressors--is overexpressed in TADCs that have been infiltrated in human
      prostate cancers and TRAMP mouse model of prostate cancers, and induces the
      expression of immune-suppressive genes including indoleamine-2,3-dioxygenase
      (IDO1), arginase (ARG1) and TGF-beta. Adoptive transfer of T helper cells or
      silencing of FOXO3 by siRNAs repressed the expression of FOXO3 gene and inhibited
      the tolerogenicity of TADCs. Therefore, inhibition of FOXO3 signals might be a
      clue for improvement of cancer immunotherapy.

PMID- 21843083
TI  - Neem leaf glycoprotein inhibits CD4+CD25+Foxp3+ Tregs to restrict murine tumor
      growth.
AB  - BACKGROUND: The presence of Tregs in tumors is associated with compromised tumor
      specific immune responses and has a clear negative impact on survival of cancer
      patients. Thus, downregulation of Tregs is considered as a promising cancer
      immunotherapeutic approach. We have reported previously that neem leaf
      glycoprotein (NLGP) prophylaxis restricts tumor growth in mice by immune
      activation. In continuation, here, involvement of NLGP in the modulation of Tregs
      in association with tumor growth restriction is investigated. RESULTS: NLGP
      downregulates CD4+CD25+Foxp3+ Tregs within tumors. NLGP-mediated downregulation
      of CCR4 along with its ligand CCL22 restricts Treg migration at the tumor site.
      NLGP is not apoptotic to Tregs but significantly downregulates the expression of
      Foxp3, CTLA4 and GITR. It also reverses the functional impairment of T-effector
      cells by Tregs, in terms of IFN-gamma secretion, cellular proliferation and tumor
      cell cytotoxicity. NLGP also facilitates reconditioning of tumor microenvironment
      (hostile) by increasing IFN-gamma and IL-12 but decreasing IL-10, TGF-beta, VEGF
      and IDO, creating an antitumor niche. Interaction between Foxp3, p-NFATc3 and p
      Smad2/3, needed for successful Treg function, is also inhibited by NLGP.
      CONCLUSION: All of these coordinated events might result in inhibition of Treg
      associated-tumor growth and therefore increased survivability of mice having NLGP
      treatment before or/and after tumor inoculation. Thus, the possibility of NLGP
      being an excellent tool as a T-cell anergy breaker by abrogating the suppressor
      functions of Tregs in cancer needs to be explored further in the clinic.

PMID- 21843085
TI  - Immunotherapy of allergic contact dermatitis.
AB  - The term 'immunotherapy' refers to treating diseases by inducing, enhancing or
      suppressing immune responses. As allergy is an excessive, detrimental immune
      reaction to otherwise harmless environmental substances, immunotherapy of
      allergic disease is aimed at the induction of tolerance toward sensitizing
      antigens. This article focuses on the historical developments, present state and
      future outlook for immunotherapy with haptens as a therapeutic modality for
      allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in
      respiratory allergies, attempts were undertaken at curing allergic contact
      dermatitis by means of controlled administration of the sensitizing haptens.
      Animal and human experiments confirmed that tolerance to haptens can be induced
      most effectively when the induction of tolerance precedes attempted
      sensitization. In real life, however, therapy is sought by people who are already
      sensitized and an effective reversal of hypersensitivity seems more difficult to
      achieve. Decades of research on Rhus hypersensitivity led to a conclusion that
      immunotherapy can suppress Rhus dermatitis, however, only to a limited degree,
      for a short period of time, and at a high risk of side effects, which makes this
      method therapeutically unprofitable. Methodological problems with most available
      studies of immunotherapy of contact allergy to nickel make any definite
      conclusions impossible at this stage.

PMID- 21843084
TI  - Successful immunotherapy of canine flea allergy with injected Actinomycetales
      preparations.
AB  - AIMS: Can heat-killed, borate-buffered suspensions of Gordonia bronchialis,
      Rhodococcus coprophilus or Tsukamurella inchonensis be used to treat canine flea
      allergy? MATERIALS & METHODS: Organisms cultured on Sauton's medium into
      stationary phase were autoclaved in borate-buffered saline and stored at 10 mg
      wet weight/ml. Intradermal injections of 0.1 ml containing 1 mg of bacilli were
      administered on the first and 20th days of the study. G. bronchialis and R.
      coprophilus were most effective in a pilot study of a small number of dogs with
      flea allergy. A larger number of affected dogs were then randomized to receive
      placebo or either of the two selected reagents. The extent and severity of
      allergic signs and symptoms were scored and blood samples were collected just
      before the first injection and 28 days after the second. RESULTS: Both selected
      reagents reduced the extent and severity of lesions (p < 0.001) and reduced
      scratching. Eosinophil numbers were reduced (p < 0.0001) between the first and
      second assessment. CONCLUSIONS: Injections of G. bronchialis or R. coprophilus
      effectively reduce the signs and symptoms of flea allergy in dogs.

PMID- 21843087
TI  - Complex interplays in immune T-cell differentiation and developmental fate
      determination.
AB  - Aspects relevant to immune T-cell differentiation and fate determination have
      been examined and discussed in the context of transcription factors, initiating
      cytokines in association with cognate antigen activation. It appears that the
      differentiation optional program, in light of recent results related to genetic
      as well as epigenetic mechanisms, is not predetermined and irreversibly fixed;
      rather, there is some degree of flexibility allowing the manipulation of
      remodeling the already differentiated effector cell subsets/lineages. From the
      progress obtained it will be possible, in the near future, to tailor and obtain
      various well-defined and efficient immune effector cell subsets/cell lineages for
      translational applications in autoimmunity, infectious diseases, graft rejection
      as well as cancer in safe conditions.

PMID- 21843086
TI  - Cryptococcus neoformans galactoxylomannan is a potent negative immunomodulator,
      inspiring new approaches in anti-inflammatory immunotherapy.
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen responsible for life
      threatening infections in immunocompromised individuals and occasionally in those
      with no known immune impairment. The fungus is endowed with several virulence
      factors, including capsular polysaccharides that play a key role in virulence.
      The capsule is composed of 90-95% glucuronoxylomannan (GXM), 5-8%
      galactoxylomannan (GalXM) and <1% mannoproteins. Capsular polysaccharides are
      shed into tissue where they produce many deleterious effects. Since GalXM has a
      smaller molecular mass, the molar concentration of GalXM in polysaccharide that
      is shed could exceed that of GXM in C. neoformans exopolysaccharides. Moreover,
      GalXM exhibits a number of unusual biologic properties both in vitro and in vivo.
      Here, we summarize the principal immunomodulatory effects of GalXM described
      during the last 20 years, particularly the mechanisms leading to induction of
      apoptosis in T lymphocytes, B lymphocytes and macrophages. Since the capacity of
      GalXM to induce widespread immune suppression is believed to contribute to the
      virulence of C. neoformans, this property might be exploited therapeutically to
      dampen the aberrant activation of immune cells during autoimmune disorders.

PMID- 21843089
TI  - Facemask use by children during infectious disease outbreaks.
AB  - An overview of available literature on the use of protective facemasks by
      children for protection from respiratory infectious agents reveals relatively few
      articles dealing specifically with the topic, despite their use during recent
      outbreaks (eg, severe acute respiratory syndrome, pandemic influenza). Little is
      known about the physiological and psychological burdens imposed by these devices
      and a child's ability to correctly use and tolerate them. This article focuses on
      the myriad issues associated with protective facemask use by children in the hope
      of educating public health personnel, healthcare professionals, and families on
      their limitations and associated risks, and in the hope of fostering much-needed
      research.

PMID- 21843090
TI  - Predicting participation in ultrasound hip screening from message framing.
AB  - The use of ultrasound (US) screening for developmental dysplasia of the hip (DDH)
      is an innovation in preventive child health care in the Netherlands. What is not
      known is whether parents will accept this screening method and will actually
      participate in it. It is widely known that health behaviors can be influenced by
      the framing of information. The objective of this study was to examine the
      influence of a gain- versus loss-framed brochure on parental participation in US
      screening for DDH. In total, 4150 parents of infants born between August 2007 and
      December 2008 received either a gain-framed or a loss-framed brochure. Parents
      could participate in the screening when their infant was 3 months old. The
      participation rate in the US screening was 74.3%. In contrast to the predictions
      of prospect theory, the results indicated that parents who had received the gain
      framed message were more likely to participate in the screening compared to
      parents who had received the loss-framed message. This effect may be explained by
      the low risk perception of parents and by the possibility that the screening was
      perceived as a health-affirming behavior rather than an illness-detecting
      behavior. To increase participation rates, it is recommended that parents be
      informed about the positive aspects of partaking in screening for DDH.

PMID- 21843091
TI  - Web 2.0 and health communication.

PMID- 21843092
TI  - The prospects for Web 2.0 Technologies for Engagement, Communication, and
      Dissemination in the Era of Patient-Centered Outcomes Research: selected articles
      developed from the Eisenberg Conference Series 2010 Meeting.

PMID- 21843093
TI  - Realizing the promise of Web 2.0: engaging community intelligence.
AB  - Discussions of Health 2.0, a term first coined in 2005, were guided by three main
      tenets: (a) health was to involve more participation, because an evolution in the
      web encouraged more direct consumer engagement in their own health care; (b) data
      was to become the new "Intel Inside" for systems supporting the vital decisions
      in health; and (c) a sense of collective intelligence from the network would
      supplement traditional sources of knowledge in health decision making. Interests
      in understanding the implications of a new paradigm for patient engagement in
      health and health care were kindled by findings from surveys such as the National
      Cancer Institute's Health Information National Trends Survey, showing that
      patients were quick to look online for information to help them cope with
      disease. This article considers how these 3 facets of Health 2.0--participation,
      data, and collective intelligence--can be harnessed to improve the health of the
      nation according to Healthy People 2020 goals. The authors begin with an
      examination of evidence from behavioral science to understand how Web 2.0
      participative technologies may influence patient processes and outcomes, for
      better or worse, in an era of changing communication technologies. The article
      then focuses specifically on the clinical implications of Health 2.0 and offers
      recommendations to ensure that changes in the communication environment do not
      detract from national (e.g., Healthy People 2020) health goals. Changes in the
      clinical environment, as catalyzed by the Health Information Technology for
      Economic and Clinical Health Act to take advantage of Health 2.0 principles in
      evidence-based ways, are also considered.

PMID- 21843094
TI  - Dissemination 2.0: closing the gap between knowledge and practice with new media
      and marketing.
AB  - Despite substantial investments in public health and clinical research at the
      national level, and significant advancements in these areas of science, few
      evidence-based programs and services are rapidly implemented in health care or
      public health practice as a result of failures of dissemination. A significant
      gap in current processes to disseminate and implement effective programs relates
      to the lack of systems and infrastructure to facilitate distribution of
      scientific research products to potential end users, including clinicians and
      other practitioners. In this article, the authors assert that Web 2.0
      technologies can be leveraged to enhance dissemination efforts and increase the
      implementation of evidence-based programs and services in everyday practice. The
      authors describe the research-to-practice delivery process and highlight gaps in
      the supply chain necessary to translate research findings into evidence-based
      practice. The authors critically evaluate the 4 most prominent strategies
      currently used to promote dissemination and implementation of research evidence
      in practice, and they detail how each can be improved by leveraging Web 2.0
      technologies to enhance dissemination of research evidence. Last, the authors
      provide examples and suggestions for capitalizing on Web 2.0 technologies to
      enhance dissemination efforts and ensure that evidence-based research products
      reach intended end users and are implemented in clinical practice.

PMID- 21843095
TI  - Using Web 2.0 technologies to enhance evidence-based medical information.
AB  - This article invokes research on information seeking and evaluation to address
      how providers of evidence-based medical information can use Web 2.0 technologies
      to increase access to, enliven users' experiences with, and enrich the quality of
      the information available. In an ideal scenario, evidence-based medical
      information can take appropriate advantage of community intelligence spawned by
      Web 2.0 technologies, resulting in the ideal combination of scientifically sound,
      high-quality information that is imbued with experiential insights from a
      multitude of individuals. To achieve this goal, the authors argue that people
      will engage with information that they can access easily, and that they perceive
      as (a) relevant to their information-seeking goals and (b) credible. The authors
      suggest the utility of Web 2.0 technologies for engaging stakeholders with
      evidence-based medical information through these mechanisms, and the degree to
      which the information provided can and should be trusted. Last, the authors
      discuss potential problems with Web 2.0 information in relation to decision
      making in health contexts, and they conclude with specific and practical
      recommendations for the dissemination of evidence-based health information via
      Web 2.0 technologies.

PMID- 21843096
TI  - The potential of cellular technology to mediate social networks for support of
      chronic disease self-management.
AB  - Productive interactions among patients, friends/family, and health care
      providers, as outlined by the Chronic Care Model, are important for promoting
      adherence to recommended care and good health outcomes among adults with a
      chronic illness. Characteristics of these interactions--active participation,
      collaboration, and data sharing among constituents--are the same as those of
      social networks organized around Web 2.0 principles and technology. Thus, the Web
      2.0 framework can be used to configure social networks without the inherent
      spatiotemporal constraints of face-to-face interactions that remain prevalent in
      health care delivery. In this article, the author outlines various design
      principles and decisions for a pilot study in which cellular technology was used
      to mediate interactions between adults with Type 2 diabetes and supporters (i.e.,
      family members or friends selected by the patients who agree provide support) to
      motivate regular self-monitoring of blood glucose (among the diabetes
      participants). Participants generally found the network to be relatively easy to
      use. Some diabetes patients reported improved attention to self-monitoring; and,
      patient-selected supporters indicated improvements in emotional and instrumental
      support that should benefit diabetes patients' lifestyle and health.

PMID- 21843097
TI  - Exploring the potential of Web 2.0 to address health disparities.
AB  - This article addresses use of the Internet and Web 2.0 technologies by racial and
      ethnic minorities and explores the potential opportunities and challenges in
      leveraging Web 2.0 approaches to impact health disparities. These opportunities
      and challenges include developing approaches and methods to (a) identify
      strategies for integrating social media into health promotion interventions
      focused on major health-related issues that affect members of medically
      underserved groups; (b) amalgamate techniques to leverage and connect social
      media technologies to other evidence-informed online resources; (c) integrate
      health communication best practices, including addressing health literacy issues;
      (d) capitalize on social networking to enhance access and communication with
      health care providers; and (e) advance current efforts and ongoing expansion of
      research participation by individuals from underserved communities.

PMID- 21843098
TI  - News coverage of health-related issues and its impacts on perceptions: Taiwan as
      an example.
AB  - This article examines how health news gets framed and the influence of exposure
      to news framed differently. A content analysis of Taiwanese newspapers indicates
      that health news in general, and H1N1 flu news in particular, is more likely to
      use alarm rather than coping frames. According to an experiment, exposure to H1N1
      flu news in an alarm frame evokes greater fear and increases perceived severity
      and vulnerability, though it does not help develop prevention and treatment
      efficacy. A survey of the general public also shows that attention and exposure
      to televised news coverage of the H1N1 flu are associated with greater levels of
      worry and perceptions of the severity of and vulnerability to this health
      problem, but they are not related to issue knowledge, detection, or prevention
      efficacy. Thus, it is important for news coverage to provide information that
      increases the audience's efficacy when alerting it to health threats.

PMID- 21843099
TI  - Why addressing the poor and underinsured is vexing.

PMID- 21843100
TI  - The Relationship between female sexual arousal and response bias in women with
      and without provoked vestibulodynia.
AB  - Smaller correlations have typically been found between genital and subjective
      sexual arousal in female versus male samples. This study evaluated the
      association between response bias and the relationship between genital and
      subjective arousal (i.e., concordance) in women with (n = 20) and without (n =
      21) provoked vestibulodynia. Participants (M = 21.27 years, SD = 2.27) underwent
      blood flow imaging via a laser Doppler imager to assess genital responsiveness to
      a visual erotic stimulus; subjective arousal was assessed during and following
      the film. The relationships between three types of subjective arousal ratings
      (perceived sexual arousal, perceived genital responsiveness, and reported desire
      to engage in sexual activity) and two forms of socially desirable responding
      (impression management and self-deceptive enhancement) were examined. Concordance
      estimates were statistically non-significant in both groups, with the exception
      of the desire to engage in sexual activity, which was moderately correlated with
      genital arousal in the control group. Impression management was not a
      statistically significant moderator of the relationship between genital and
      subjective arousal, but was moderately negatively related to the three forms of
      subjective arousal ratings in the provoked vestibulodynia group. The results
      highlight the importance of assessing response bias in laboratory studies
      comparing women with and without sexual dysfunction.

PMID- 21843102
TI  - Child injury prevention in Vietnam: achievements and challenges.
AB  - As with other South Asian countries, injury is becoming a leading cause of death
      and morbidity among children in Vietnam. In response to the increasing burden of
      child injury, government and non-government agencies in Vietnam have combined
      efforts during the last decade to develop and implement various child injury
      prevention strategies and programmes. This article provides, through a review of
      relevant documents and interviews with major stakeholders, an overview of these
      efforts and highlights major challenges to child injury prevention in the
      country. The findings point to notable achievements in terms of increasing
      awareness of injury facing children at all levels in the community and developing
      a sound injury prevention policy framework in a relatively short period of time.
      However, much needs to be done to implement necessary environmental and
      legislative changes, strengthen child injury surveillance and injury prevention
      research; and to improve access to health services. The insight into the
      experience of Vietnam could benefit other low- and middle-income countries with a
      high burden of child injury.

PMID- 21843103
TI  - Risk of anti-EGFR monoclonal antibody-related hypomagnesemia: systematic review
      and pooled analysis of randomized studies.
AB  - INTRODUCTION: The typical class side effect of anti-epidermal growth factor
      receptor (EGFR) monoclonal antibodies (panitumumab and cetuximab) is a cutaneous
      maculopapular rash, although hypomagnesemia is also described to be a frequent
      adverse event. The purpose of our meta-analysis is to evaluate the frequency and
      the relative risk of hypomagnesemia in patients treated with cetuximab or
      panitumumab in randomized trials. AREA COVERED: Eligible studies included
      prospective randomized Phase III controlled trials in which cetuximab or
      panitumumab were compared with standard anti-neoplastic therapy or best
      supportive care. Summary incidence rates and relative risks with 95% confidence
      intervals were calculated. EXPERT OPINION: The overall incidence of
      hypomagnesemia was 17% among the patients who received the treatment, whose risk
      of developing hypomagnesemia turned out to be significantly increased compared
      with the patients treated with control medication, with an overall relative risk
      of 5.83 (p < 0.00001), where 3.87 refers to cetuximab and 12.55 to panitumumab.
      The addition of anti-EGFR monoclonal antibodies to standard anticancer therapy
      showed a significantly increased risk of hypomagnesemia compared with controls.
      The risk seems to be even higher for panitumumab, probably correlated with the
      increased risk of other adverse events (e.g., diarrhea and dehydration).
      Hypomagnesemia does not seem to be linked with any serious complications.

PMID- 21843104
TI  - Laboratory markers of mast cell and basophil activation in monitoring rush
      immunotherapy in bee venom-allergic children.
AB  - AIM: To evaluate markers of mast cell and basophil activation in children
      undergoing the initial phase of honeybee venom immunotherapy (VIT). PATIENTS &
      METHODS: Five children (four boys and one girl) aged 9.5-18 years with severe
      systemic bee sting reactions and confirmed IgE-mediated allergy were enrolled.
      Plasma and urine concentrations of 9alpha,11beta-PGF2 and serum tryptase levels
      were measured at four time points and peripheral blood basophil count and CD63
      expression were measured at three time points in the course of VIT, including 5
      day rush initial immunotherapy (cumulative dose of 223 ug of bee venom allergen)
      and two subsequent maintenance doses of 100 ug. RESULTS: In the first 40 days of
      VIT, there was a decrease in mean plasma levels of 9alpha,11beta-PGF2 (from 41.5
      to 27.9 pg/ml; p < 0.05), accompanied by an increase in baseline basophil
      activation (from 2 to 15%; p < 0.05). The median serum tryptase levels increased
      from 3.45 to 4.40 ng/ml during rush phase and subsequently returned to initial
      values (statistically not significant). In four patients, the basophil activation
      test in response to bee venom allergens remained positive throughout the study.
      The fifth patient was basophil activation test-negative at all three
      measurements, and a post hoc analysis revealed clinical peculiarities that are
      discussed in the paper. CONCLUSIONS: Our preliminary results indicate that plasma
      levels of 9alpha,11beta-PGF2 decrease while numbers of activated basophils
      increase during the initial phase of bee venom rush immunotherapy in children.

PMID- 21843105
TI  - Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) inhibitors.
AB  - Inhibitors of topoisomerase I (Top1) that result in stalled Top1 cleavage
      complexes (Top1cc) are commonly employed against cancer. Combination chemotherapy
      with DNA repair inhibitors can potentially improve response to these widely used
      chemotherapeutics. One line of inquiry focuses on inhibitors of tyrosyl-DNA
      phosphodiesterase 1 (Tdp1), a repair enzyme for Top1cc. Tdp1 catalyzes the
      hydrolysis of DNA adducts covalently linked to the 3'-phosphate of DNA, including
      Top1-derived peptides and also 3'-phosphoglycolates. Tdp1 inhibitors should
      synergize not only with Top1-targeting drugs (camptothecins,
      indenoisoquinolines), but also with bleomycin, topoisomerase II (Top2) inhibitors
      (etoposide, doxorubicin) and DNA alkylating agents. Here, we summarize the
      structure-activity relationship obtained from the reported Tdp1 inhibitors.
      Better understanding of Top1cc repair in vivo coupled with detailed structural
      studies on Tdp1-inhibitor interaction will be crucial in guiding the rational
      design of Tdp1 inhibitors.

PMID- 21843107
TI  - The redesigned follitropin alfa pen injector: results of the patient and nurse
      human factors usability testing.
AB  - OBJECTIVES: A redesigned pen injector for administration of follitropin alfa
      (follitropin alpha) has been developed for use in fertility treatment cycles. Pre
      summative and summative usability testing was undertaken to assess the risk of
      dosing errors compared with the existing follitropin alpha pen. The study also
      assessed proper use of and dose selection with the redesigned pen. METHODS:
      Infertile women who were trying to conceive and specialist nurses were recruited
      from four cities in Germany. Usability goals relating to proper use of the pen
      device were defined from a risk assessment and further categorized as critical
      and functional operational goals. Individual, non-interventional, standardized,
      usability tests were performed with patients and nurses by four experienced
      research professionals using questionnaires that also included ease-of-use
      ratings. A non-standardized qualitative analysis of nurse-patient training
      sessions was performed in the presence of a research professional; reasons for
      confidence, safety, possible misunderstandings and risks when handling the pen
      were noted. RESULTS: The overall risk of dosing errors with the redesigned pen
      was not higher than with the existing pen. No unexpected operational risks and no
      major concerns regarding the risk of misuse or dosing errors were identified.
      CONCLUSIONS: The study provides useful practical information on the redesigned
      pen from both patient and nurse perspectives.

PMID- 21843108
TI  - PAMUS: placenta accreta management across the United States.
AB  - OBJECTIVE: There is lack of consensus regarding the optimal strategy for
      management of abnormal placentation. We set out to determine the actual practices
      of providers across the United States (U.S.). METHODS: This was a cross-sectional
      survey of maternal-fetal medicine providers in the U.S. registered with the
      Society for Maternal Fetal Medicine (SMFM). Questions regarding management
      strategies for placenta accreta were addressed by the survey. Both univariable
      and multivariable analyses were performed to determine if a relationship between
      demographic factors and management strategies exists. RESULTS: Approximately 64%
      of responders were male and 62% had been in practice less than or equal to 20
      years. The respondents represented all the major regions of the U.S. and the
      majority had performed one to five cases in the past year. The gestational age at
      delivery varied by both the number of years in practice and by geographic
      location. About 35% of providers report the use of ureteral stents and 36% of
      providers use internal femoral artery balloons though this varied by region.
      Regional differences and recent experience play a role in whether to attempt
      placental removal first. Though the majority of providers believe hysterectomy is
      the only management option for accreta, 32% of providers have attempted
      conservative management. CONCLUSIONS: There is wide variation in the actual
      practices of physicians in the U.S. with regard to management of placenta
      accreta.

PMID- 21843109
TI  - Rhesus monkey cardiosphere-derived cells for myocardial restoration.
AB  - BACKGROUND AIMS: Cardiosphere-derived cells (CDC) have been proposed as a
      promising myocardial stem cell source for cardiac repair. They have been isolated
      from human, porcine and rodent cardiac biopsies. However, their usefulness for
      myocardial restoration remains controversial. We aimed to determine the survival,
      differentiation and functional effects of Rhesus monkey CDC (RhCDC) in a mouse
      model of myocardial infarction. METHODS: RhCDC were isolated and characterized by
      flow cytometry and reverse transcriptase (RT)-polymerase chain reaction (PCR) and
      compared with human CDC. They were injected intramyocardially into severe
      combined immune deficiency (SCID) beige mice after ligature of the left anterior
      descending artery (LAD). Phosphate-buffered saline (PBS) served as placebo.
      Medium treatment alone was used to distinguish between cellular and non-cellular
      effects. Animals were divided into a non-infarcted control group (n = 7), infarct
      control groups (n = 24), medium-treated infarct groups (n = 35) and RhCDC-treated
      infarct groups (n = 33). Follow-up was either 1 or 4 weeks. LV function was
      assessed by pressure-volume loop analysis. Differentiation was analyzed by
      immunhistochemical profiling and RT-PCR. RESULTS: Proliferating RhCDC grafts were
      detected after transplantation in an acute infarct model. RhCDC as well as medium
      treatment protected myocardium within the infarct area and improved LV function.
      RhCDC had a superior regenerative effect than medium alone. CONCLUSIONS: For the
      first time, RhCDC have been used for the restoration of infarcted myocardium.
      RhCDC proliferated in vivo and positively influenced myocardial remodeling. This
      effect could be mimicked by treatment with unconditioned medium alone,
      emphasizing a non-cellular paracrine therapeutic mechanism. However, as a robust
      cardiac stem cell source, CDC might be useful to evoke prolonged paracrine
      actions in cardiac stem cell therapy.

PMID- 21843111
TI  - Fetal hydronephrosis: does adding an extra parameter improve detection of
      neonatal uropathies?
AB  - OBJECTIVE: The aim of this study is to assess the correlation of the average
      antero-posterior, transverse and longitudinal diameters of the fetal renal pelvis
      to neonatal outcome. METHODS: This retrospective study evaluates the neonatal
      outcome of all fetuses with suspected pyelectasis on ultrasonographic examination
      between May 1997 and March 2006. During this time, 764 fetuses with pyelectasis
      and 1285 renal units were scanned. We defined fetal pyelectasis as mild if the
      ARP was >= 5-<10 mm, moderate if ARP >= 10-<15 mm and severe if ARP >= 15 mm. A
      total of 612 fetuses met the inclusion criteria. The Corteville criteria in the
      third trimester (antero-posterior diameter >= 7 mm) and an antero-posterior
      diameter (AP) of >= 10 mm were compared with the ARP and likelihood ratio's
      calculated. Ultrasonographic evaluation took place in the third trimester if
      fetal pyelectasis was diagnosed as an isolated finding in the second trimester.
      This last ultrasonographic examination was used for final analysis and as a
      guideline for postnatal follow-up. Neonatal outcome was assessed by reviewing
      medical records, ultrasonographic, renographic and voiding cysto-urethrographic
      results. RESULTS: Of all the fetuses diagnosed with renal pelvis dilatation in
      the third trimester of pregnancy, 73 (11.9%) infants needed postnatal surgery.
      The majority of the postnatal surgery was performed in the group of fetuses with
      severe hydronephrosis (8.2%). This resulted in a LR of 5.81 and a post-test
      probability of 61.3%. In total, 78.8% of the fetuses with hydronephrosis had
      spontaneous resolution across all grades of severity on the first postnatal
      ultrasonogaphic investigation or during their follow-up. In 9.3% of the cases,
      uropathies were diagnosed, but no surgical intervention had taken place during
      the follow-up period. Using the Corteville criteria as gold standard for the
      third trimester (AP >= 7 mm), 11 (1.8%) patients would not have been diagnosed
      with uropathies. And in the case of AP >= 10 mm, 5.1% of the cases would have
      been missed. CONCLUSION: An ARP of >= 5 mm in the second and/or third trimester
      of pregnancy enables a better detection of patients with uropathies and
      indication for surgery as compared with AP >= 10 mm, but renders almost similar
      results compared with the Cortville criteria (AP >= 7 mm) in the third trimester.

PMID- 21843110
TI  - Immediate versus delayed switch from levodopa/carbidopa to
      levodopa/carbidopa/entacapone: effects on motor function and quality of life in
      patients with Parkinson's disease with end-of-dose wearing off.
AB  - OBJECTIVE: Assess motor function and quality of life (QoL) in Parkinson's disease
      (PD) subjects with end-of-dose wearing off (EODWO), comparing immediate and
      delayed switch (IS, DEL) to levodopa/carbidopa/entacapone (LCE). BACKGROUND: LCE
      treatment improves motor function in PD patients with EODWO. Correlations with
      QoL have not been previously assessed. METHODS: A 16-week, prospective,
      randomized, multicenter, open-label study in PD subjects on stable
      levodopa/carbidopa (LC) doses with EODWO. The IS subjects switched to LCE at
      baseline; DEL subjects at week 4. The primary efficacy variable was UPDRS III
      score (baseline to week 4). QoL measurements (PDQUALIF, PDQ-39) were assessed at
      baseline, weeks 4, 8, and study endpoint. RESULTS: The intent-to-treat population
      comprised 350/359 patients (IS, n = 177; DEL, n = 173). A significant decrease in
      UPDRS III scores at week 4 was observed (IS, 3.7U, p < .0001; DEL, 1.8U, p =
      .0018). Group differences favored IS (1.9U, p = .0148). At week 8, IS subjects
      had significant total score decreases in PDQUALIF (2.5U, p = .0133) and PDQ-39
      (5.8U, p = .0001). In the mobility and activities of daily living PDQ-39
      subdomains, IS subjects had significantly larger week 4 decreases (versus DEL p =
      .0331 and p = .0125, respectively). Adverse events included diarrhea (14.5%),
      nausea (12.3%), and dizziness (8.4%). CONCLUSION: The IS provided greater motor
      improvement at week 4 and improved QoL at week 8.

PMID- 21843112
TI  - alpha1-antitrypsin insufficiency is a possible contributor to preterm premature
      rupture of membranes.
AB  - OBJECTIVE: alpha1-antitrypsin (AAT) is protective of tissue damage induced by
      enzymes of inflammatory cell source. Inflammatory cells are involved in preterm
      labor, preterm premature rupture of membrane (PPROM) and term premature rupture
      of membrane (PROM). The purpose of this research was to examine whether plasma
      concentration and activity of AAT differ between these manifestations. METHODS:
      In a prospective case control study, blood samples were assayed for AAT
      concentration and activity in 71 individuals. AAT concentration and activity were
      measured by standard methods. RESULTS: No significant differences were found
      between AAT levels (p = 0.497) and activity (p = 0.879) in preterm and term
      labor. AAT levels and activity in PPROM and PROM were not significantly different
      as well (p = 0.748 and p = 0.880, respectively). While 69 out of 71 patients
      displayed normal circulating levels of AAT, 2 PPROM patients out of 15 had
      abnormally low, previously undiagnosed,AAT concentrations, and had subsequently
      developed complications that were absent in the other groups. CONCLUSIONS: No
      statistically significant differences were demonstrated in the levels of AAT
      between patients with preterm and term labor, nor between preterm and term PROM.
      Yet, unexpectedly, patients that had marked AAT deficiency belonged exclusively
      to the PPROM group.

PMID- 21843113
TI  - Solving the problems of practice-based education.

PMID- 21843114
TI  - Unintended pregnancy in Australia: what more can we do?

PMID- 21843116
TI  - Australian dispensing doctors' prescribing: quantitative and qualitative
      analysis.
AB  - OBJECTIVE: To evaluate the prescribing practices of Australian dispensing doctors
      (DDs) and to explore their interpretations of the findings. DESIGN, PARTICIPANTS
      AND SETTING: Sequential explanatory mixed methods. The quantitative phase
      comprised analysis of Pharmaceutical Benefits Scheme (PBS) claims data of DDs and
      non-DDs, 1 July 2005-30 June 2007. The qualitative phase involved semi-structured
      interviews with DDs in rural and remote general practice across Australian
      states, August 2009-February 2010. MAIN OUTCOME MEASURES: The number of PBS
      prescriptions per 1000 patients and use of Regulation 24 of the National Health
      (Pharmaceutical Benefits) Regulations 1960 (r. 24); DDs' interpretation of the
      findings. RESULTS: 72 DDs' and 1080 non-DDs' PBS claims data were analysed
      quantitatively. DDs issued fewer prescriptions per 1000 patients (9452 v 15 057;
      P = 0.003), even with a similar proportion of concessional patients and patients
      aged > 65 years in their populations. DDs issued significantly more r. 24
      prescriptions per 1000 prescriptions than non-DDs (314 v 67; P = 0.008).
      Interviews with 22 DDs explained that the fewer prescriptions were due to
      perceived expectation from their peers regarding prescribing norms and the need
      to generate less administrative paperwork in small practices. CONCLUSIONS:
      Contrary to overseas findings, we found no evidence that Australian DDs
      overprescribed because of their additional dispensing role.

PMID- 21843115
TI  - Predictors of accuracy of diagnosis of chronic obstructive pulmonary disease in
      general practice.
AB  - OBJECTIVES: To compare the clinical diagnosis of chronic obstructive pulmonary
      disease (COPD) with results of post-bronchodilator spirometry in general
      practice, and examine practitioner, practice and patient characteristics
      associated with agreement between clinical and spirometric diagnoses. DESIGN,
      SETTING AND PARTICIPANTS: General practitioners from practices in Sydney
      identified eligible patients aged 40-80 years seen in the past year and
      prescribed respiratory medications whom they regarded as having COPD. Between
      November 2006 and April 2008, we collected information on the GPs and their
      practices, and demographic information, smoking status, comorbidities,
      respiratory medicines use, vaccination status, quality of life and spirometry
      results for participating patients. MAIN OUTCOME MEASURES: Frequency of COPD
      diagnosis on spirometry; odds ratios for characteristics associated with
      agreement between clinical and spirometric diagnoses. RESULTS: 56 GPs from 44
      practices participated in the study. Of 1144 eligible patients, 445 were
      recruited (mean age, 65 years; 49% male). Of these, 257 (57.8%) had post
      bronchodilator spirometry consistent with COPD +/- asthma, 16 (3.6%) had asthma
      only, 82 (18.4%) had normal spirometry, and 90 (20.2%) had other spirometric
      diagnoses. Having a spirometer in the practice was not predictive of agreement
      between clinical and spirometric diagnoses. Older patient age was significantly
      associated with correct diagnosis, while higher numbers of comorbidities were
      associated with misdiagnosis. CONCLUSIONS: A substantial proportion of patients
      clinically identified as having COPD in general practice do not have the
      condition according to spirometric criteria, with inaccurate diagnosis more
      common in patients with comorbidities. Policy and practice change is needed to
      support the use of spirometry in primary care.

PMID- 21843117
TI  - Taking a stab.

PMID- 21843118
TI  - Referral pathways in colorectal cancer: findings from a qualitative study in
      general practice.

PMID- 21843119
TI  - General practice and preventive health care: a view through the eyes of community
      members.
AB  - OBJECTIVE: To identify barriers to, and enablers of, the uptake of preventive
      care in general practice from the perspective of community members, and to
      explore their sense of the effectiveness of that care. DESIGN, PARTICIPANTS AND
      SETTING: Qualitative study involving 18 focus groups comprising 85 community
      members aged over 25 years, from two areas of metropolitan Melbourne that were
      identified as being of high and low socioeconomic status (SES). The study was
      performed between 25 May and 9 December 2010. Groups were stratified by age, sex
      and location (high or low SES). MAIN OUTCOME MEASURES: Factors related to
      practitioners, patients and structure and organisation that may act as barriers
      to and/or enablers of preventive care in general practice. RESULTS: Participants
      saw preventive care as legitimate in general practice when it was associated with
      concrete action or a test, but rated their general practitioners as poor at
      delivering prevention. Trust, rapport and continuity of care were viewed as
      enablers for participants to engage in prevention with their GP. Barriers to
      participants seeking preventive care through their GPs included lack of knowledge
      about what preventive care was relevant to them, consultations focused
      exclusively on acute-care concerns, time pressures and the cost of consultations.
      CONCLUSIONS: A disconnect exists between patient perceptions of prevention in
      general practice and government expectations of this sector at a time when
      general practice is being asked to increase its focus and effectiveness in this
      field.

PMID- 21843120
TI  - The Refugee Health Network of Australia: towards national collaboration on health
      care for refugees.

PMID- 21843121
TI  - Access to primary health care services by community-based asylum seekers.
AB  - OBJECTIVES: To determine whether community-based asylum seekers experience
      difficulty in gaining access to primary health care services, and to determine
      the impact of any difficulties described. DESIGN, SETTING AND PARTICIPANTS:
      Qualitative study using semi-structured interviews between September and November
      2010. Participants were community-based asylum seekers who attended the Asylum
      Seekers Centre of New South Wales, and health care practitioners and staff from
      the Asylum Seekers Centre and the NSW Refugee Health Service. RESULTS: We
      interviewed 12 asylum seekers, three nurses, one general practitioner and one
      manager. Asylum seekers' responses revealed that their access to primary health
      care was limited by a range of barriers including Medicare ineligibility, health
      care costs and the effects of social, financial and psychological stress. Limited
      access contributed to physical suffering and stress in affected asylum seekers.
      Participants providing care noted some improvement in access after recent
      government policy changes. However, they noted inadequate access to general
      practitioners, and dental, mental health and maternity care, and had difficulty
      negotiating pro-bono services. Both groups commented on the low availability of
      interpreters. CONCLUSIONS: Access to primary health care in Australia for
      community-based asylum seekers remains limited, and this has a negative effect on
      their physical and mental health. Further action is needed to improve the
      affordability of health care and to increase the provision of support services to
      community-based asylum seekers; extending Medicare eligibility would be one way
      of achieving this.

PMID- 21843122
TI  - Sex of the GP--20 years on.
AB  - OBJECTIVE: Previous research with the Australian Morbidity and Treatment Survey
      (1990-1991) showed significant differences in general practitioner
      characteristics and patient mix of male and female GPs. Even after adjusting for
      these, it was seen that male and female GPs managed different types of medical
      conditions. The proportion of female GPs increased from 19.6% in 1990-1991 to
      37.1% in 2009-2010. This study investigates whether differences remain two
      decades later. DESIGN AND SETTING: Analysis of 2009-2010 Bettering the Evaluation
      and Care of Health (BEACH) data examining GP characteristics, patient encounter
      characteristics, patient reasons for encounter (RFE), problem types managed and
      management methods used, by GP sex. Whether GP sex was an independent predictor
      of problem types being managed, or management methods used, was tested using
      multiple logistic regressions and Poisson regression. PARTICIPANTS: 988 GPs
      recorded 98 800 GP-patient encounters. MAIN OUTCOME MEASURE: Adjusted differences
      in clinical activity of male and female GPs. RESULTS: After adjustment, compared
      with male GPs, females recorded more RFEs about general and unspecified issues
      and endocrine, female genital, pregnancy and family planning problems; and fewer
      concerning the musculoskeletal, respiratory, skin and male genital systems.
      Female GPs managed more general and unspecified, digestive, circulatory,
      psychological, endocrine, female genital and social problems; recorded nearly 20%
      more clinical treatments and referrals; recorded nearly 10% more imaging and
      pathology tests; and 4.3% fewer medications. CONCLUSIONS: After two decades, even
      with increased numbers of female GPs, the differences in problems managed by male
      and female GPs remain, and will probably continue. Female GPs use more resources
      per encounter, but may not use more resources in terms of annual patient care.

PMID- 21843123
TI  - Chronic disease management items in general practice: a population-based study of
      variation in claims by claimant characteristics.
AB  - OBJECTIVE: To describe how Medical Benefits Schedule (MBS) chronic disease (CD)
      item claims vary by sociodemographic and health characteristics in people with
      heart disease, asthma or diabetes. DESIGN, SETTING AND PARTICIPANTS: A cross
      sectional analysis of linked unit-level MBS and survey data from the first
      102,934 participants enrolled in the 45 and Up Study, a large-scale cohort study
      in New South Wales, who completed the baseline survey between January 2006 and
      July 2008. MAIN OUTCOME MEASURE: Claim for any general practitioner CD item
      within 18 months before enrolment, ascertained from MBS records. RESULTS: The
      proportion of individuals making claims for MBS CD items was 18.5% for asthma,
      22.3% for heart disease, and 44.9% for diabetes. Associations between participant
      characteristics and a claim for a CD item showed similar patterns across the
      three diseases. For heart disease and asthma, people most likely to claim a CD
      item were women, older, of low income and education levels, with multiple chronic
      conditions, fair or poor self-rated health, obesity and low physical activity
      levels. The pattern of claims was slightly different for participants with
      diabetes in that there was no significant association with number of chronic
      conditions, smoking or physical activity. CONCLUSIONS: Many individuals with self
      reported CD do not claim CD items. People with diabetes and individuals with
      greatest need based on health, socioeconomic and lifestyle risk factors are the
      most likely to claim CD items.

PMID- 21843124
TI  - Ram's horn nails.

PMID- 21843125
TI  - Increased bulk-billing for general practice consultations in regional and remote
      areas, 2002-2008.

PMID- 21843126
TI  - The general practitioner's role in providing mental health services to
      Australians, 1997 and 2007: findings from the national surveys of mental health
      and wellbeing.
AB  - OBJECTIVES: To compare the findings of the 1997 and 2007 Australian national
      surveys of mental health and wellbeing (NSMHWBs) with respect to the role of
      general practitioners in providing mental health services. DESIGN, SETTING AND
      PARTICIPANTS: There were 10,641 participants Australia-wide in the 1997 survey
      and 8841 in the 2007 survey. Data were gathered through face-to-face interviews
      using a written questionnaire. MAIN OUTCOME MEASURES: Rates of use of GPs and
      other health care providers for treatment of mental health problems; levels of
      met and unmet need for mental health services reported by those accessing GP
      services. RESULTS: Between 1997 and 2007, the proportion of people accessing any
      mental health care service within the previous 12 months increased significantly,
      from 12.4% to 21.4% (P < 0.01), although the proportion accessing GP care for
      mental health problems did not increase. In both surveys, nearly 60% of
      individuals with self-assessed mental health problems sought no professional help
      for their problems, although about 80% of these non-users had seen GPs about
      other matters. The proportions of participants who reported receiving sufficient
      information, medication and/or therapy for their mental health problem increased
      significantly over the 10-year period. However, unmet need for information also
      increased. In both surveys, over 90% of participants aged 60 years or over with
      self-assessed mental health problems reported obtaining no help for their mental
      health problem despite seeing a GP for other reasons. CONCLUSION: Despite a
      significant rise in the use of mental health services, the role of GPs in
      providing such services has not increased.

PMID- 21843127
TI  - How generalisable are results of studies conducted in practice-based research
      networks? A cross-sectional study of general practitioner demographics in two New
      South Wales networks.
AB  - OBJECTIVE: To compare the demographics of general practitioners in two practice
      based research networks (PBRNs) and to explore the generalisability of research
      findings from these PBRNs. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional
      questionnaire-based study of two geographically-based PBRNs--Hunter New England
      Central Coast Network of Research General Practices (NRGP) and Primary Healthcare
      Research Network-General Practice (PHReNet-GP)--during August-September 2010. All
      183 GP members of both PBRNs were invited to participate; of these, 140 (77%)
      participated. MAIN OUTCOME MEASURES: GPs' demographics, use of languages other
      than English in consultations, and previous participation in research. Practices'
      use of practice nurses. Socioeconomic status and rurality or urbanicity of
      practice location. RESULTS: Compared with PHReNet-GP GPs, NRGP GPs were more
      likely to work in a practice employing a practice nurse (100% v 53.8%; 95% CI for
      difference, 30.5%-61.8%; P < 0.001), worked in larger practices (2.9 more full
      time-equivalent GPs per practice; 95% CI, 2.1-3.6; P < 0.001), and were less
      likely to work in a major city (33.7% v 89.7%; 95% CI for difference, 42.8%
      69.3%; P < 0.001). NRGP GPs also worked in practices with a different spectrum of
      socioeconomic disadvantage, and were less likely to have been involved in
      research as a researcher (35.4% v 76.9%; 95% CI for difference, 25.3%-57.8%; P <
      0.001). Fewer NRGP GPs consulted in languages other than English (8.9% v 64.1%;
      95% CI for difference, 39.1%-71.2%; P < 0.001). There were also differences
      between these and national general practice statistics. CONCLUSIONS: These
      results suggest possible lack of generalisability of findings from some types of
      studies conducted in single PBRNs. In such circumstances, collaboration of PBRNs
      may produce more generalisable results.

PMID- 21843128
TI  - Keeping the connection.

PMID- 21843129
TI  - Lessons for Australian primary care reform from New Zealand, that great change
      laboratory.

PMID- 21843130
TI  - When big isn't beautiful: lessons from England and Scotland on primary health
      care organisations.
AB  - United Kingdom primary care trusts resembled the primary health care
      organisations (PHCOs) that have been proposed for Australia--for example,
      Medicare Locals. They resulted in a loss of innovation, creativity, motivation
      and morale among general practitioners and other front-line staff. English
      primary care trusts are being abolished and L80 billion will be handed over to GP
      commissioners. Management theory and practical experience shows repeatedly the
      dangers of reorganising into larger units. Lessons for Australia are to defer
      deciding on the size of PHCOs until their purposes are clear, to enshrine the
      principle of subsidiarity, and to opt for networking of the current Divisions of
      General Practice over mergers. So far, debate on the functions and structures of
      PHCOs has been muted. It is now time for vigorous debate.

PMID- 21843131
TI  - Can we trust the PCEHR not to leak?

PMID- 21843132
TI  - In-practice and distance consultant on-call general practitioner supervisors for
      Australian general practice?
AB  - Increasing numbers of medical students and junior doctors learn and work in
      general practice. Increased supervisory responsibilities for general
      practitioners threaten the quality of care provided to patients and the income
      thus derived. Incremental changes to infrastructure and funding are welcome, but
      insufficient. Alternative models must be funded, trialled and evaluated. One such
      model, involving consultant on-call GP supervisors, is proposed.

PMID- 21843136
TI  - NHMRC funding for primary health care research, 2000-2008.

PMID- 21843137
TI  - Teaching and patient payment.

PMID- 21843140
TI  - High throughput technologies in drug discovery.

PMID- 21843142
TI  - Support vector machine based prediction of P. falciparum proteasome inhibitors
      and development of focused library by molecular docking.
AB  - The emergence and spread of Plasmodium falciparum resistance to existing
      antimalarials emphasize the impelling search for novel drug targets and
      chemotherapeutic compounds. The ubiquitin-proteasome system plays a major role in
      overall protein turnover, in eukaryotic cells including plasmodia. 20S beta
      subunit is the catalytic core of this proteolytic machinery, and hence most of
      the inhibitors developed are being targeted towards this component. Inhibition of
      the proteasome is established as a promising strategy to develop novel
      antimalarial drugs. The present study reports identification of novel drug-like
      20S proteasome inhibitors with potential activity against the 20S beta subunit of
      P. falciparum using a combination of ligand based (Support Vector Machines) and
      receptor based (molecular docking) techniques. The robust learning and
      generalizing capability of Support Vector Machines (SVM) has been exploited to
      classify proteasome inhibitors and non-inhibitors, targeted towards P. falciparum
      20S proteasome. SVM model has been trained using 170 molecular descriptors of 64
      inhibitors and 208 putative non-inhibitors of 20S proteasome. The non-linear
      classifier based on Radial Basis Function (RBF) kernel yielded highest
      classification accuracy in comparison to the linear classifier. The best
      classifier had 5-fold Cross-Validation (CV) accuracy of 97% and Area Under Curve
      (AUC) of 0.99 reflecting good accuracy of the model. The SVM model rapidly
      classified compounds with potential proteasomal activity. Subsequently, molecular
      docking studies aided the generation of focused collection of compounds with good
      binding affinity towards the substrate-binding site of 20S beta subunit. The
      novel drug-like 20S proteasome inhibitors identified in this study can be a good
      starting point to develop novel antimalarial drugs.

PMID- 21843143
TI  - Integration of virtual and high throughput screening in lead discovery settings.
AB  - In the last decade mass screening strategies became the main source of leads in
      drug discovery settings. Although high throughput (HTS) and virtual screening
      (VS) realize the same concept the different nature of these lead discovery
      strategies (experimental vs theoretical) results that they are typically applied
      separately. The majority of drug leads are still identified by hit-to-lead
      optimization of screening hits. Structural information on the target as well as
      on bound ligands, however, make structure-based and ligand-based virtual
      screening available for the identification of alternative chemical starting
      points. Although, the two techniques have rarely been used together on the same
      target, here we review the existing prominent studies on their true integration.
      Various approaches have been shown to apply the combination of HTS and VS and to
      better use them in lead generation. Although several attempts on their
      integration have only been considered at a conceptual level, there are numerous
      applications underlining its relevance that early-stage pharmaceutical drug
      research could benefit from a combined approach.

PMID- 21843141
TI  - Discovery of cationic polymers for non-viral gene delivery using combinatorial
      approaches.
AB  - Gene therapy is an attractive treatment option for diseases of genetic origin,
      including several cancers and cardiovascular diseases. While viruses are
      effective vectors for delivering exogenous genes to cells, concerns related to
      insertional mutagenesis, immunogenicity, lack of tropism, decay and high
      production costs necessitate the discovery of non-viral methods. Significant
      efforts have been focused on cationic polymers as non-viral alternatives for gene
      delivery. Recent studies have employed combinatorial syntheses and parallel
      screening methods for enhancing the efficacy of gene delivery, biocompatibility
      of the delivery vehicle, and overcoming cellular level barriers as they relate to
      polymer-mediated transgene uptake, transport, transcription, and expression. This
      review summarizes and discusses recent advances in combinatorial syntheses and
      parallel screening of cationic polymer libraries for the discovery of efficient
      and safe gene delivery systems.

PMID- 21843144
TI  - Current trends in virtual high throughput screening using ligand-based and
      structure-based methods.
AB  - High throughput in silico methods have offered the tantalizing potential to
      drastically accelerate the drug discovery process. Yet despite significant
      efforts expended by academia, national labs and industry over the years, many of
      these methods have not lived up to their initial promise of reducing the time and
      costs associated with the drug discovery enterprise, a process that can typically
      take over a decade and cost hundreds of millions of dollars from conception to
      final approval and marketing of a drug. Nevertheless structure-based modeling has
      become a mainstay of computational biology and medicinal chemistry, helping to
      leverage our knowledge of the biological target and the chemistry of protein
      ligand interactions. While ligand-based methods utilize the chemistry of
      molecules that are known to bind to the biological target, structure-based drug
      design methods rely on knowledge of the three-dimensional structure of the
      target, as obtained through crystallographic, spectroscopic or bioinformatics
      techniques. Here we review recent developments in the methodology and
      applications of structure-based and ligand-based methods and target-based
      chemogenomics in Virtual High Throughput Screening (VHTS), highlighting some case
      studies of recent applications, as well as current research in further
      development of these methods. The limitations of these approaches will also be
      discussed, to give the reader an indication of what might be expected in years to
      come.

PMID- 21843145
TI  - Cloud computing approaches to accelerate drug discovery value chain.
AB  - Continued advancements in the area of technology have helped high throughput
      screening (HTS) evolve from a linear to parallel approach by performing system
      level screening. Advanced experimental methods used for HTS at various steps of
      drug discovery (i.e. target identification, target validation, lead
      identification and lead validation) can generate data of the order of terabytes.
      As a consequence, there is pressing need to store, manage, mine and analyze this
      data to identify informational tags. This need is again posing challenges to
      computer scientists to offer the matching hardware and software infrastructure,
      while managing the varying degree of desired computational power. Therefore, the
      potential of "On-Demand Hardware" and "Software as a Service (SAAS)" delivery
      mechanisms cannot be denied. This on-demand computing, largely referred to as
      Cloud Computing, is now transforming the drug discovery research. Also,
      integration of Cloud computing with parallel computing is certainly expanding its
      footprint in the life sciences community. The speed, efficiency and cost
      effectiveness have made cloud computing a 'good to have tool' for researchers,
      providing them significant flexibility, allowing them to focus on the 'what' of
      science and not the 'how'. Once reached to its maturity, Discovery-Cloud would
      fit best to manage drug discovery and clinical development data, generated using
      advanced HTS techniques, hence supporting the vision of personalized medicine.

PMID- 21843146
TI  - Virtual high throughput screening in new lead identification.
AB  - Drug discovery continues to be one of the greatest contemporary challenges and
      rational application of modelling approaches is the first important step to
      obtain lead compounds, which can be optimised further. Virtual high throughput
      screening (VHTS) is one of the efficient approaches to obtain lead structures for
      a given target. Strategic application of different screening filters like
      pharmacophore mapping, shape-based, ligand-based, molecular similarity etc., in
      combination with other drug design protocols provide invaluable insights in lead
      identification and optimization. Screening of large databases using these
      computational methods provides potential lead compounds, thus triggering a
      meaningful interplay between computations and experiments. In this review, we
      present a critical account on the relevance of molecular modelling approaches in
      general, lead optimization and virtual screening methods in particular for new
      lead identification. The importance of developing reliable scoring functions for
      non-bonded interactions has been highlighted, as it is an extremely important
      measure for the reliability of scoring function. The lead optimization and new
      lead design has also been illustrated with examples. The importance of employing
      a combination of general and target specific screening protocols has also been
      highlighted.

PMID- 21843147
TI  - Modern drug discovery technologies: opportunities and challenges in lead
      discovery.
AB  - The identification of promising hits and the generation of high quality leads are
      crucial steps in the early stages of drug discovery projects. The definition and
      assessment of both chemical and biological space have revitalized the screening
      process model and emphasized the importance of exploring the intrinsic
      complementary nature of classical and modern methods in drug research. In this
      context, the widespread use of combinatorial chemistry and sophisticated
      screening methods for the discovery of lead compounds has created a large demand
      for small organic molecules that act on specific drug targets. Modern drug
      discovery involves the employment of a wide variety of technologies and expertise
      in multidisciplinary research teams. The synergistic effects between experimental
      and computational approaches on the selection and optimization of bioactive
      compounds emphasize the importance of the integration of advanced technologies in
      drug discovery programs. These technologies (VS, HTS, SBDD, LBDD, QSAR, and so
      on) are complementary in the sense that they have mutual goals, thereby the
      combination of both empirical and in silico efforts is feasible at many different
      levels of lead optimization and new chemical entity (NCE) discovery. This paper
      provides a brief perspective on the evolution and use of key drug design
      technologies, highlighting opportunities and challenges.

PMID- 21843148
TI  - Vitamin E-related inhibition of monocyte 5-lipoxygenase and cardiovascular
      outcome in maintenance hemodialysis patients.
AB  - A daily supplement of vitamin E is recommended for the secondary prevention of
      cardiovascular events in end-stage renal disease patients on maintenance
      hemodialysis. Vitamin E has been entrusted with therapeutic properties against
      cardiovascular disease for more than 60 years. Several epidemiological studies
      and intervention trials have been performed with vitamin E, and some of them
      showed that it prevents atherosclerosis. For a long time, vitamin E was assumed
      to act by decreasing the oxidation of low-density lipoproteins, a key step in
      atherosclerosis initiation. However, at the cellular level vitamin E interferes
      with smooth muscle cell proliferation, platelet aggregation, monocyte adhesion,
      and oxidized low-density lipoproteins uptake and cytokine production, all
      reactions implied in the progression of atherosclerosis. Recent research points
      out that these effects may be not only the result of the antioxidant activity of
      vitamin E but also of its distinct molecular actions. These biological properties
      of vitamin E may allow to design better strategies for primary and secondary
      prevention of cardiovascular disease, with a potential exploitation of vitamin E
      supplements in primary and secondary prevention of major adverse cardiovascular
      events in all uremic patients. In this review, we also outline relevant patents
      on vitamin E and lipoxygenase inhibitors.

PMID- 21843149
TI  - Development of novel drug delivery prototypes devices for targeted delivery drug
      therapy at the molecular level in aqueous media.
AB  - A novel approach in target specific molecular prototype drug delivery system
      concerns the attempt to employ radical affording substances (RAS) or radical
      quenching substances (RQS) as prodrugs able to produce irreversible damage on the
      desired target and therefore to stimulate cellular apoptosis. However, radical
      species generated can react quickly within the chemical environment prior to
      reaching its proper site of action. In this short communication, we report our
      investigations towards developing two alternative novel, simple, flexible and
      effective drug delivery systems that provide optimal dosage of drugs precisely
      where and when needed and therefore achieve and sustain a complex delivery
      profile. We have demonstrated the application of two effective molecular
      prototype delivery systems able to harness free radical reactivity within the
      laboratory where biological processes can be studied and controlled, leading to
      the prevention of disease and the development of new treatments for disease
      states mediated by free radicals.

PMID- 21843150
TI  - Emerging role of hydrogen sulfide in health and disease: critical appraisal of
      biomarkers and pharmacological tools.
AB  - H2S (hydrogen sulfide) is a well known and pungent gas recently discovered to be
      synthesized enzymatically in mammalian and human tissues. In a relatively short
      period of time, H2S has attracted substantial interest as an endogenous gaseous
      mediator and potential target for pharmacological manipulation. Studies in
      animals and humans have shown H2S to be involved in diverse physiological and
      pathophysiological processes, such as learning and memory, neurodegeneration,
      regulation of inflammation and blood pressure, and metabolism. However, research
      is limited by the lack of specific analytical and pharmacological tools which has
      led to considerable controversy in the literature. Commonly used inhibitors of
      endogenous H2S synthesis have been well known for decades to interact with other
      metabolic pathways or even generate NO (nitric oxide). Similarly, commonly used
      H2S donors release H2S far too quickly to be physiologically relevant, but may
      have therapeutic applications. In the present review, we discuss the enzymatic
      synthesis of H2S and its emerging importance as a mediator in physiology and
      pathology. We also critically discuss the suitability of proposed 'biomarkers' of
      H2S synthesis and metabolism, and highlight the complexities of the currently
      used pharmacological H2S 'donor' molecules and 'specific' H2S synthesis
      inhibitors in their application to studying the role of H2S in human disease.

PMID- 21843151
TI  - A dynamic scaffolding mechanism for rhodopsin and transducin interaction in
      vertebrate vision.
AB  - The early steps in vertebrate vision require fast interactions between Rh
      (rhodopsin) and Gt (transducin), which are classically described by a collisional
      coupling mechanism driven by the free diffusion of monomeric proteins on the disc
      membranes of rod and cone cells. Recent findings, however, point to a very low
      mobility for Rh and support a substantially different supramolecular
      organization. Moreover, Rh-G(t) interactions seem to possibly occur even prior to
      light stimuli, which is also difficult to reconcile with the classical scenario.
      We investigated the kinetics of interaction between native Rh and G(t) in
      different conditions by surface plasmon resonance and analysed the results in the
      general physiological context by employing a holistic systems modelling approach.
      The results from the present study point to a mechanism that is intermediate
      between pure collisional coupling and physical scaffolding. Such a 'dynamic
      scaffolding', in which prevalently dimeric Rh and G(t) interact in the dark by
      forming transient complexes (~25% of G(t) is precoupled to Rh), does not slow
      down the phototransduction cascade, but is compatible with the observed
      photoresponses on a broad scale of light stimuli. We conclude that Rh molecules
      and Rh-G(t) complexes can both absorb photons and trigger the visual cascade.

PMID- 21843152
TI  - Changing landscapes.

PMID- 21843153
TI  - Parenteral nutrition for patients with advanced ovarian malignancy.
AB  - BACKGROUND: Parenteral nutrition (PN) in patients with disseminated ovarian
      cancer remains controversial. The role of PN in providing nutrition and improving
      quality of life is unclear. The present study aimed to determine the pattern of
      prescribing in a large teaching hospital, and to identify subgroups where the use
      of PN was justified. METHODS: Sixty-five patients with advanced ovarian carcinoma
      received PN between January 2002 and May 2008. A retrospective case note review
      was undertaken to retrieve data on PN prescribing and outcomes in terms of
      duration of PN provision, complications, and survival. RESULTS: Three subgroups
      were identified. Group I consisted of 18 (28%) patients who received PN for a
      median [interquartile range (IQR)] of 5 (2-11) days. The majority of these 18
      patients (n = 13, 72%) had disease-related terminal bowel obstruction. Out of 18
      of these patients, 17 (95%) had poor performance status. The median (IQR)
      survival was 12 (6-28) days. Group II consisted of 40 (61%) patients who were re
      established on enteral nutrition. The median (IQR) duration of PN administration
      was 10 (6-17) days. The most common indication of PN was protracted ileus (n =
      25, 63%). Out of 40 of these patients, 35 (88%) patients had good performance
      status. The median (IQR) survival was 264 (96-564) days. The third group of
      patients required home PN (n = 7, 11%). Four (58%) patients had short bowel
      syndrome and three (42%) had terminal intestinal obstruction. All of the patients
      had good performance status. The median (IQR) duration of PN administration and
      survival was 241 (90-305) days. CONCLUSIONS: Administration of PN appears to be
      justified in those patients with a good performance status (i.e. patients capable
      of self-care), which constituted three-quarters of this cohort. In the remaining
      patients with poor performance status, and particularly those with terminal
      intestinal obstruction, PN administration was difficult to justify. PN should not
      be denied based purely on the pathology, although cautious judgment is required
      to select those who are most likely to benefit.

PMID- 21843154
TI  - An evaluation of an Internet-based approach to weight loss with low glycaemic
      load principles.
AB  - BACKGROUND: The prevalence of overweight and obesity is increasing worldwide at
      an alarming rate. An Internet-based weight-loss programme has the potential to
      reach larger numbers of people than traditional face-to-face programmes. A
      growing body of evidence supports the use of low glycaemic load (GL) diets for
      weight loss. The present study aimed to investigate the efficacy of an Internet
      based weight-loss programme that included foods with a low GL. METHODS: One
      hundred and three volunteers, with a body mass index (BMI) >=28 kg m(-2) ,
      enrolled into an Internet weight-loss programme. A dietitian counselled
      participants over the Internet via weekly interactive chat rooms and monthly e
      mails. Participants self-recorded body weight and food intake directly on to the
      Internet site. Weight, BMI and waist circumference were measured, and dietary
      data collected, at baseline and 6 months. RESULTS: Seventy participants completed
      the 6-month weight-loss programme. Among these, mean weight, BMI and waist
      circumference significantly decreased by 3.5 kg (95% CI = 2.3-4.7), 1.2 kg m(-2)
      (95% CI = 0.8-1.7) and 4.8 cm (95% CI = 2.8-6.8), of baseline values respectively
      (P < 0.001). Twenty-five (36%) of the 70 participants lost a clinically
      significant amount of weight (>5% of initial body weight). CONCLUSIONS: This
      descriptive study has shown that an Internet-based weight-loss programme with low
      GL principles can promote weight loss. This type of intervention and approach
      could be used to enhance other weight-loss strategies.

PMID- 21843155
TI  - Current literature.

PMID- 21843156
TI  - Patterns of rabies occurrence in Bhutan between 1996 and 2009.
AB  - This study was conducted to evaluate incidence and seasonal trends of rabies in
      dogs and other domestic animals in Bhutan from 1996 to 2009. Time series analysis
      approach was used to determine the seasonal trend and temporal association
      between species-specific rabies cases in animals. A total of 814 rabies cases
      were reported during the 14-year period, of which cattle and domestic dogs
      accounted for 55% (447/814) and 39% (317/814) of the cases, respectively. The
      remaining 6% of the cases (50/814) were reported in horses (2%), cats (2%), pigs
      (1%) and goats (1%). Rabies cases were reported throughout the year with more
      reports during spring and summer months. The annual patterns of cases were stable
      from 1996 to 2005, but the incidence increased during 2006 and 2008. Fifty-nine
      of the 205 sub-districts reported rabies in animals from 1996 to 2009 with
      increased incidences in the four districts in southern Bhutan, an area located
      close to the border towns of India. A significant (P < 0.05) positive cross
      correlation was observed between the number of cases in dogs and other domestic
      animals at time lags (months) 1-3 with the highest correlation (r = 0.94, P <
      0.05) observed at time lag 0 (same month) indicating that the peak in rabies
      incidences occur in the same month when both dogs and other domestic animal cases
      are reported. Regression analysis predicted rabies in other domestic animal when
      there are reports of rabies in dogs during the previous months. This study
      provides useful information about the epidemiology of rabies that can be used to
      plan a rabies control programme in Bhutan.

PMID- 21843158
TI  - Anti-ageing--fact, fiction or faction?

PMID- 21843159
TI  - Palatal and mandibular tori in a Romanian removable denture-wearing population.
AB  - OBJECTIVE: To establish the prevalence of palatal tori (TP) and mandibular tori
      (TM) in a Romanian denture-wearing population in order to see how or if tori
      influenced the denture design or the treatment planning. BACKGROUND DATA:   There
      are no available data regarding tori in an elderly Romanian population and its
      implication for treatment planning. It could be considered a local factor
      influencing the quality of prosthetic treatment. MATERIAL AND METHOD: Tori
      prevalence was investigated in 251 patients, with an average age of 62years. A
      statistical analysis was made, using odds ratio (OR) for the distribution related
      to gender and the Chi-squared test for the differences in prevalence related to
      age groups. Treatment planning difficulties because of presence of tori were
      recorded. RESULTS: Frequency of TP was significantly higher in both genders
      (OR=2.0661 and p=0.0446) and non-significant frequency for distribution between
      genders for TM (OR=0.9421 and p=0.8273). The differences in age groups showed
      both tori types have a variable prevalence related to age. The most frequent
      location for TP was found in the posterior one-third and two-thirds of the palate
      and for TM in the canine and first premolar area presenting with different sizes.
      CONCLUSIONS: Tori prevalence in our study group is high and is significantly
      related to age (p<0.05) having a peak at over 60 years. The preferential site of
      TP in the posterior palatal area and this location has an impact on decision
      making in treatment planning for the upper denture.

PMID- 21843160
TI  - Replacing a failed implant adjacent to the implant-supported restoration in the
      anterior region after ridge augmentation procedure.
AB  - BACKGROUND: Dental professionals will have to deal with more implant failure and
      related complications due to the increase in popularity of this form of therapy.
      OBJECTIVES: There have been only a few reports on replacing failed implants at
      the same sites. This report may provide more detailed information about the re
      implantation procedure and the results to the operator and less motivated
      patient. MATERIALS AND METHODS: The implant failure occurred after a 3-year
      period of loading in the anterior region. next to an implant-supported
      prosthesis. Ridge augmentation was performed with staged placement of an implant.
      RESULTS: The implant was re-installed after ridge augmentation with deproteinised
      bovine bone and absorbable membrane, with the implant-supported prosthesis
      functioning well up to the final evaluation. CONCLUSION: This case report shows
      the possibility of treating the failed implant in the older population using a
      staged approach and it may give more detailed information about the re
      implantation procedure and results to the operator and less motivated patient.
      Further evaluations over longer periods are necessary to establish whether this
      procedure offers long-term benefits to patients.

PMID- 21843163
TI  - Methods to counter scientific misconduct in medical journals: text-matching
      software programs.

PMID- 21843164
TI  - Re: 'Risk factors for gestational diabetes mellitus: implications for the
      application of screening guidelines'. Teh WT, Teede HJ, Paul E et al. ANZJOG
      2011; 51: 26-30.

PMID- 21843167
TI  - Why has radiotherapy utilisation not improved since 1999?

PMID- 21843168
TI  - Are we ready for dual-time point FDG PET imaging?

PMID- 21843169
TI  - Comparison of readers' detection of right-sided and left-sided breast cancers and
      microcalcifications.
AB  - INTRODUCTION: Aim of this study was to determine if there is a statistically and
      clinically significant difference in diagnostic performance (cancer diagnosis)
      and perceptual performance (microcalcification detection) when detecting left
      sided or right-sided breast cancers and microcalcifications. METHODS: Eight
      radiologist readers (8-20 years experience in radiology, five current
      BreastScreen readers) read a set of 100 digital mammograms (23/100 had proven
      malignancies and 52/100 had confirmed microcalcifications) for three reads
      (random case order in each read). The same mammograms were presented on two
      reads, serving as the baseline reads. The data from these reads were used to
      calculate intra-observer variability (presented in an earlier study). The
      experimental read consisted of left-right mirror images of the original
      mammograms. In each read, the radiologists were requested to 'clear' or 'call
      back' cases and to indicate if any microcalcifications (benign and malignant)
      were present on the mammograms. Reading conditions were standardised. RESULTS:
      Comparison of intra-reader performance difference for left-sided versus right
      sided breast cancers and microcalcifications with intra-observer variability for
      breast cancer diagnosis and microcalcification detection, respectively, revealed
      no clinically significant difference between left-sided and right-sided
      detections. Per-case analysis showed more left-sided breast cancers and
      microcalcifications correctly detected. This left-right difference in detection
      did not reach statistical significance, P-value of 0.28 for cancer diagnosis and
      0.74 for microcalcification detection. CONCLUSION: There is no statistically or
      clinically significant difference between left-sided and right-sided breast
      cancer diagnosis and microcalcification detection in a group of experienced
      radiologists. Individual reading patterns do not affect detection rates of left
      sided and right-sided cancers and microcalcifications.

PMID- 21843170
TI  - Diagnostic accuracy of diffusion-weighted MRI for identifying hepatocellular
      carcinoma with liver explant correlation.
AB  - BACKGROUND: The goal of this study was to use liver explant correlation to assess
      the diagnostic accuracy of diffusion-weighted (DW)-MRI for hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Thirty-seven patients were
      retrospectively identified who had undergone liver transplantation and had
      preoperative, respiratory-triggered, single-shot echo-planar DW-MRI. Two
      independent blinded observers evaluated the DW-MRI images for HCC and comparison
      was made with the explanted specimens. RESULTS: By pathology, 29 HCCs (mean
      largest diameter 2.0 cm; range 0.7-4.0 cm) were identified in 20 patients.
      Sensitivity and specificity for reader 1 were 55 and 92%, and for reader 2 were
      45 and 100%. There was 'substantial' inter-observer agreement (kappa = 0.64).
      CONCLUSION: DW-MR is not sensitive enough for HCC to be used as a stand-alone
      sequence, although its high specificity suggests that it is likely valuable as a
      component of a liver MRI protocol.

PMID- 21843171
TI  - Usefulness of C-arm CT during superselective infusion chemotherapy for advanced
      head and neck carcinoma.
AB  - PURPOSE OF THE STUDY: To evaluate the usefulness of C-arm computed tomography
      (CT) during superselective intra-arterial infusion chemotherapy for advanced head
      and neck carcinoma. METHODS: C-arm CT was performed during superselective intra
      arterial infusion chemotherapy for 11 patients with advanced head and neck
      carcinoma located in the hypopharynx (n = 3), maxillary sinus (n = 3), oropharynx
      (n = 1), larynx (n = 1), extra-auditory canal (n = 1), tonsil (n = 1) and tongue
      (n = 1). The usefulness of C-arm CT during superselective catheterisation was
      evaluated. RESULTS: On arteriography, nine tumours showed tumour stains and two
      in the oropharynx or tonsil showed no obvious tumour stains. C-arm CT was
      performed one to four times (mean +/- standard deviation, 2.5 +/- 0.8) in each
      patient during a single procedure. C-arm CT clearly showed not only the vascular
      territory of the selected branch but also the tumour itself in all patients.
      Intra-arterial infusion chemotherapy was performed through one to three branches
      (mean, 1.7 +/- 0.9) according to C-arm CT findings without any complications.
      CONCLUSION: C-arm CT during superselective intra-arterial infusion chemotherapy
      was useful to determine the arterial supply of head and neck carcinoma. C-arm CT
      may replace conventional CT during superselective arteriography in this
      procedure.

PMID- 21843172
TI  - Adult bronchopulmonary dysplasia: computed tomography pulmonary findings.
AB  - INTRODUCTION: This study aimed to describe the structural pulmonary sequelae of
      bronchopulmonary dysplasia (BPD) in adulthood. SUBJECTS AND METHODS: Fifty-one
      adult survivors (36 females and 15 males; median age 20 years) of BPD underwent
      high-resolution inspiratory and expiratory computed tomography of the chest. The
      scans were evaluated independently by two thoracic radiologists blinded to the
      patient's clinical details using a standardised scoring system. RESULTS: Abnormal
      findings were seen in 50 (98%), the most common of which were subpleural
      triangular opacities (94%), linear opacities (90%), air trapping (65%) and
      emphysema (47%). The kappa values were derived by simplifying the score for each
      finding as present or absent. The kappa values for these findings were 0.65,
      0.20, 0.58 and 0.54, respectively. CONCLUSIONS: Common findings were triangular,
      linear opacities and gas trapping. Emphysema diagnosis was more prevalent than
      previous studies, which may have been enhanced by improved technical factors.

PMID- 21843173
TI  - Dual-time-point (18)F-FDG-PET/CT imaging in the assessment of suspected
      malignancy.
AB  - INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess
      whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging
      improved the evaluation of suspected malignancy and if there was any resulting
      change in management. METHODS: A total of 53 patients with suspected malignancy
      were investigated by performing two static acquisitions started at mean times t =
      64 and t = 155 min after the tracer injection. The total number of malignant
      lesions was 133 and the total number of benign lesions was 61. Visual and
      semiquantitative analysis was performed on both the early and delayed images.
      RESULTS: Overall, there was a significant improvement (P < 0.001) in the
      sensitivity of delayed imaging (94%) compared with early imaging (77%) in
      detecting malignant lesions, without a reduction in specificity. In 10 patients,
      13 malignant lesions were undetected on early imaging alone but detected on
      delayed imaging. In seven patients, 10 malignant lesions were incorrectly
      classified as 'likely benign' on early imaging but correctly reported as 'likely
      malignant' on delayed imaging. Management was altered in 2 out of 17 patients.
      Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual
      time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from
      benign intra-abdominal lesions but did not improve the evaluation of pulmonary
      lesions. CONCLUSIONS: (18)F-FDG-PET/CT imaging should be performed as late as
      reasonably possible after tracer administration in order to increase tumour-to
      background contrast and thereby improve the sensitivity of demonstrating
      additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in
      the evaluation of intra-abdominal lesions but does not improve the overall
      evaluation of pulmonary lesions.

PMID- 21843174
TI  - MRI in evaluation of perianal fistula.
AB  - This essay illustrates the usefulness of MRI in evaluating perianal fistulas, a
      common disease, notorious for recurrence if not assessed and treated adequately.
      MRI exquisitely depicts the perianal anatomy and shows the fistulous tracks and
      their associated ramifications and abscesses. It thus provides an excellent
      preoperative understanding of the disease, enabling selection of the most
      appropriate surgical treatment and therefore minimising all chances of
      recurrence.

PMID- 21843175
TI  - Experience of fluoroscopy-aided thoracoscopic resection of pulmonary nodule
      localised with Lipiodol in a child.
AB  - We report the case of a 12-year-old boy with a huge liver tumour 20 cm in
      diameter with multiple lung metastases. Six months after systemic chemotherapy
      was initiated, all tumours had disappeared with the exception of the liver tumour
      and a tiny lung tumour 2.5 mm in diameter. Fluoroscopy-assisted thoracoscopic
      resection of the pulmonary nodule was performed to evaluate whether viable tumour
      tissue remained in the lung lesion. Before moving the patient to the operating
      room, the nodule was marked by Lipiodol under CT fluoroscopic guidance with the
      patient under local anaesthesia. This procedure allowed correct visualisation of
      the area that should be resected.

PMID- 21843176
TI  - Dual thyroid ectopia: a case report.
AB  - Dual thyroid ectopia is a very rare clinical entity, and only 28 cases have been
      reported previously in the literature. We describe another case in which CT
      established the diagnosis preoperatively and prevented an unnecessary surgery.

PMID- 21843177
TI  - The role of radiotherapy for T4 non-melanoma skin carcinoma.
AB  - INTRODUCTION: To review outcomes of patients treated with radiotherapy (RT) for
      T4 non-melanoma skin cancer (NMSC). METHODS: A retrospective chart review was
      performed of 21 patients who received RT for T4 NMSC from 2004 to 2010. Outcomes
      of treatment efficacy, RT technique and patient morbidity were analysed. Twelve
      patients (57.1%) were treated definitively without prior treatment, five (23.8%)
      were recurrent lesions and four (19.1%) were treated postoperatively. Ten
      patients (47.6%) had evidence of bony erosion at presentation, and four (19.1%)
      had nodal disease. Intensity-modulated radiotherapy (IMRT), three-dimensional
      conformal RT and electron treatment were included RT techniques. RESULTS: Median
      follow-up was 12 months (range, 5-48 months). Twelve patients (57.1%) following
      RT required no further treatment and had no disease recurrence. Three patients
      (14.3%) required salvage treatment and are disease-free following all treatment.
      Tumours treated initially or postoperatively had improved control rates following
      RT compared with recurrent lesions (58.3% and 100% vs. 20%). Sixty percent of
      patients treated with IMRT achieved local control following RT, and 80% were
      disease-free following surgical salvage treatment. Squamous cell carcinoma (SCC)
      histology, presence of bony erosion and/or nodal disease was associated with a
      higher incidence of disease recurrence. CONCLUSIONS: Patients presenting with
      untreated lesions, smaller tumour volumes (<70 cm(3)) postoperatively, basal cell
      histology and absence of bone erosion or nodal disease have improved local
      control and outcomes. Basal cell carcinoma and SCC should be staged and treated
      as two separate disease entities. The use of IMRT for advanced skin cancer
      warrants further investigation.

PMID- 21843178
TI  - Assessment of prostatic fiducial marker introduction: patient morbidity, staff
      satisfaction and improved treatment field placement.
AB  - INTRODUCTION: Increased accuracy when using fiducial markers for prostate
      localisation is well documented. This project aimed to establish the improvement
      in accuracy when using gold markers for daily prostate localisation, to assess
      patient satisfaction and morbidity from the transrectal implantation of gold seed
      markers and establish staff attitudes towards the newly introduced processes.
      METHODS: Twenty patients with prostate cancer had three gold seeds implanted into
      the base, apex and central zone of the prostate transrectally using ultrasound
      guidance. Surveys were conducted to assess staff and patient satisfaction with
      the process of gold seed localisation. The gold markers were used to localise the
      prostate on a daily basis using megavoltage electronic portal imaging.
      Measurements were taken to establish the increase in accuracy when using gold
      fiducial markers compared with using the surrounding bony anatomy. RESULTS: Inter
      fraction motion (1 standard deviation (SD)) of the fiducial markers was 2.20,
      4.28 and 4.27 mm in the LR, SI and AP directions, respectively. Intra-fraction
      prostate motion (1 SD) was measured as 0.8 mm LR, 1.1 mm SI and 2.0 mm AP. The
      patient survey showed that the insertion and associated side effects were
      acceptable, with 5% of patients stating that the seed insertion was worse than
      the prostate biopsy, and 23.1% of patients experienced short duration (1-2 days)
      haematuria. The staff survey showed that daily online image guidance was
      achievable without affecting patient throughput. Thirty percent of treatment
      staff believed that performing online daily localisation did not add any extra
      time to a standard treatment, and the remaining 70% thought that the added time
      was minimal (2-4 min). CONCLUSIONS: Gold fiducial markers are an accurate,
      reliable and tolerable method of daily prostate localisation.

PMID- 21843179
TI  - Work engagement in cancer workers in Queensland: the flip side of burnout.
AB  - INTRODUCTION: The study aimed to investigate factors associated with work
      engagement and burnout in cancer workers in Queensland. METHODS: A cross
      sectional survey of 579 cancer workers in Queensland was undertaken. Burnout was
      measured using the Oldenberg Burnout Inventory (OLBI) and work engagement was
      measured using the Utrecht Work and Well-being Survey. Multiple regression
      analyses were performed to identify explanatory variables that were independently
      associated with burnout and work engagement. RESULTS: The survey response rate
      was 57%. Total levels of burnout and work engagement in the sample were 31.1% and
      34.5%, respectively. Multiple regression analyses showed that shift work, 6-9
      years experience, working >20 hours/week, administrative professional stream and
      being single were associated with higher levels of burnout. There was a positive
      association between work engagement and nonshift workers, <5 years experience,
      medical and allied health workers, and workers >45 years of age. In this study,
      gender, income, hours of direct patient care, location of the centre in regional
      centres or within the private setting did not have an independent effect on the
      levels of burnout or work engagement. There was a negative association between
      burnout and work engagement (P < 0.001). CONCLUSIONS: Approximately one-third of
      the workers sampled reported burnout. Conversely, one-third reported being highly
      engaged in their work. Further research is required to study the effectiveness of
      interventions to improve personal resources and prevent burnout. Understanding
      the factors associated with work engagement is equally important in designing
      organisational programs to enhance employee engagement.

PMID- 21843180
TI  - A decade of investment in radiotherapy in New South Wales: why does the gap
      between optimal and actual persist?
AB  - BACKGROUND: There is a gap between optimal and actual radiotherapy utilization
      (RTU) rates in New South Wales (NSW). It is uncertain if this is because these
      investments have been insufficient to meet demand, or demand has been over
      estimated. In this study we assess trends in infrastructure, staffing and
      productivity in NSW over the last 10 years. METHODS: The NSW Radiotherapy
      Management Information System reports annually on activity including new
      patients, new courses, retreatments, attendances, radiotherapy fields and Area
      Health Service (AHS) of residence. Data are obtained from interstate radiotherapy
      departments that treat NSW residents. A census of equipment and staffing is
      reported. RTU was defined as the number of new cases in a year treated by
      radiotherapy divided by the number of new cases of cancer in that year. RESULTS:
      From 1999 to 2008, 115,941 NSW residents received at least one course of
      radiotherapy. During this time period there were 325,965 new diagnoses of cancer
      reported by the Central Cancer Registry. RTU was 38% in 1999 and in 2008. The
      number of linear accelerators increased from 34 to 42 between 1999 and 2008 but
      the number of accelerators per 1000 new cases of cancer remained static at 1.2.
      For AHSs, there was a significant relationship between more linear accelerators
      per 1000 patients and higher RTU (P = 0.0023). CONCLUSION: Radiotherapy
      utilization in NSW has remained at 38% for the period 1999 to 2008 because
      investment in new facilities only just kept pace with the increase in the number
      of new cases of cancer with an indication for radiotherapy. Some regional AHS
      have shown significant increases in RTU with new facilities.

PMID- 21843181
TI  - Sparing of the hippocampus, limbic circuit and neural stem cell compartment
      during partial brain radiotherapy for glioma: a dosimetric feasibility study.
AB  - INTRODUCTION: The aim of this study was to assess the feasibility of sparing
      contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and
      limbic circuit during partial brain radiotherapy (PBRT). METHODS AND MATERIALS:
      Treatment plans were generated for five hemispheric high-grade gliomas, five
      hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each,
      standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as
      IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem
      cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for
      late effects (BED(late effects)) was generated for limbic circuit, hippocampus
      and NSC. Per cent relative reduction in mean physical dose and BED was calculated
      for each plan (standard vs. sparing). RESULTS: We were able to reduce physical
      dose and BED(late effects) to these critical structures by 23.5-56.8% and 23.6
      66%, respectively. CONCLUSION: It is possible to spare contralateral limbic
      circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas
      using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem
      low-grade gliomas. This approach may reduce late cognitive sequelae of cranial
      radiotherapy.

PMID- 21843183
TI  - Academic self-concept in high school: predictors and effects on adjustment in
      higher education.
AB  - Academic self-concept is considered a relevant psychological construct
      influencing many educational outcomes directly or indirectly. Therefore, the
      major focus of the current study is on the predictors and effects of academic
      self-concept in late adolescence. First, we studied the simultaneous effects of
      individual, class-average and school-average achievement (i.e., assessed by
      school grades) on academic self-concept in the final year of high school, thereby
      replicating and extending previous research on the big-fish-little-pond effect
      model. Second, the predictive value of high school academic self-concept for
      academic adjustment and success in the first year of higher education was
      examined. The sample comprised 536 twelfth grade students (44% boys) recruited
      from 24 schools (67 classes) that were representative with regard to geographical
      region and educational network in Flanders. Structural equation modeling showed
      that, when examining the joint contribution of school- and class-average
      achievement, only class-average achievement was significantly and negatively
      associated with academic self-concept. Furthermore, a significant effect of
      academic self-concept in high school on academic adjustment and success in higher
      education (in addition to any effects of high school academic achievement) was
      found. These results highlight the importance of considering academic self
      concept in educational research and policy.

PMID- 21843184
TI  - Corporal punishment of children: changing the culture.

PMID- 21843186
TI  - Physical punishment of children: can we continue to accept the status quo?
AB  - All children require discipline, although physical punishment is just one form of
      discipline. Parental use of physical punishment is inter-generational. There is
      now evidence that physical punishment of children is not only less effective than
      other forms of discipline but can also lead to aggressive behaviour in childhood
      and adult life. Twenty-nine countries, including New Zealand, have laws against
      physical punishment in the home. Australian attitudes are slowly changing in
      favour of less use of physical punishment, but there is a long way to go. As
      advocates for children, paediatricians should not be content to accept the status
      quo.

PMID- 21843187
TI  - From small beginnings: the euthanasia of children with disabilities in Nazi
      Germany.
AB  - Although they are the lesser known Nazi atrocities, it is estimated that some
      5000-8000 children with physical and intellectual disabilities were killed in
      Nazi Germany under a programme of euthanasia. Chronologically, they were a
      precedent, being the Nazis' first organised and systematic killing programme that
      would later enlarge to include adults with disabilities and ultimately, to the
      broader programme of racially motivated 'euthanasia' of the holocaust. The
      programme intimately involved medical staff, including a number of
      paediatricians, many of whom would go unpunished and continue to practice for
      many years after the war. This paper outlines the origins and development of the
      programme, examines how families were involved and affected and looks at what
      motivated the medical staff involved with the killing. The history of the Nazi
      child euthanasia programme has a number of important lessons for practicing
      doctors and health policy-makers in the 21st century.

PMID- 21843188
TI  - Treatment experiences of children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - AIM: To gain insight into the treatment experiences of children and adolescents
      diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHODS:
      Convenience sampling was used to recruit eligible parents and carers at
      paediatric clinics of the Children's, Youth and Women's Health Service to
      participate in an interview to discuss experiences, using a semi-structured
      questionnaire. RESULTS: Thirty-five interviews were conducted. Twenty-five
      subjects had trialled an average of 1.5 interventions prior to receiving an ADHD
      diagnosis, namely, dietary modifications (46%), behavioural therapy (24%),
      learning assistance (8%) and natural remedies (8%). Following an ADHD diagnosis,
      25 subjects tried an average of 2.8 interventions, most commonly behavioural
      therapies (48%), expressive therapies (48%) and fish oil (36%). All subjects
      started psychostimulant medication after receiving an ADHD diagnosis. Despite 52%
      of parents expressing initial reluctance towards psychostimulants, 97% reported
      positive experiences with use in terms of schooling, social interaction and
      family life. Of those being treated with psychostimulants, 22 (73%) were
      concurrently using other treatments at the time of interview. CONCLUSIONS: Few
      patients use psychostimulant medication in isolation, with the majority of
      parents using multiple approaches to manage their child's behaviour. Parents
      tried a variety of therapies before commencing psychostimulant medication, often
      because of fears regarding psychostimulant safety. Parents were generally happy
      with the results gained; however adolescents interviewed were less convinced of
      the benefits of psychostimulants.

PMID- 21843190
TI  - Beware the lymphopenia: a case of severe combined immunodeficiency.
AB  - We present a case of a 2-month-old boy with partially treated meningitis and
      suspected Pneumocystis carinii pneumonia. A full blood count revealed profound
      lymphopenia. The child was diagnosed with adenosine deaminase deficiency, a rare
      cause of severe combined immunodeficiency (SCID). SCID is an immunological
      emergency and must be considered in any lymphopaenic infant with opportunistic
      infection. We discuss adenosine deaminase-deficient SCID, which can involve
      multiple systems and in which other treatment options apart from bone marrow
      transplant are available.

PMID- 21843191
TI  - How effective is adenoidectomy alone for treatment of obstructive sleep apnoea in
      a child who presents with adenoid hypertrophy?

PMID- 21843192
TI  - A yellow-brown plaque on the scalp.

PMID- 21843193
TI  - Fatal anaphylaxis in a 15-year-old boy with Down syndrome.

PMID- 21843194
TI  - Neonatal resuscitation performance.

PMID- 21843195
TI  - First study of the F508del mutation in Malaysian children diagnosed with cystic
      fibrosis.

PMID- 21843196
TI  - Enhanced magnetic resonance imaging of Guillain-Barre syndrome.

PMID- 21843198
TI  - My, your and our needs for safety and security: relatives' reflections on using
      information and communication technology in dementia care.
AB  - AIM: The present paper reports on a study aimed at describing relatives'
      reflections on different kinds of information and communication technology (ICT)
      devices that are used or can be used in the daily care of persons with dementia.
      BACKGROUND: Many persons with dementia continue living in their own homes, which
      requires the support of their relatives. One way to meet the needs of relatives
      and persons with dementia is to use ICT. METHODS: An interview study was
      conducted in Sweden (2007-2008) with a purposive sample of 14 spouses of a person
      with dementia. Qualitative content analysis was used to identify categories and
      themes in the data. FINDINGS: Relatives' reflections on the use of ICT were
      described as ICT - a support in daily life, ICT - internal and external
      conditions and ICT - the decision to use or not use. Based on these categories, a
      theme was revealed: shifting between different perspectives: my, your and our
      needs for safety and security. CONCLUSION: Relatives struggle to create a
      situation of safety and security in daily life for themselves and the persons
      with dementia. ICT devices with the right functionality and used at the right
      time are regarded as useful in solving everyday problems. In the decision to use
      or not use ICT, the opportunity to create a safe and secure environment
      overshadows potential ethical problems. Providing early information about ICT to
      persons with dementia and their relatives could facilitate joint decision-making
      regarding use of ICT.

PMID- 21843199
TI  - Factors associated with the use of institutional long-term care in Japan.
AB  - AIM: Institutionalization is a potential cost burden for long-term care (LTC)
      systems in many developed countries. Japan implemented an LTC insurance system in
      April 2000 and control of institutionalization has been one of its major issues.
      This study used over 2.1 million national representative administrative records
      to determine the factors that contribute to care use and the availability of
      local LTC facilities associated with the use of institutional LTC in Japan.
      METHODS: Factors associated with the 1-year institutional use of individuals were
      examined by a multivariate logistic regression analysis. In addition, we
      determined the impact of the regional capacities of LTC and medical institutions
      and the regional deviations of institutional LTC use using standardized use rates
      estimated from the demography and disability levels of regional LTC users.
      RESULTS: We found that subjects aged 85 years or older had more than twice as
      high a risk as those aged less than 74 years and that the risk of use increased
      more than eight times at the highest disability level. In addition, the regional
      capacity of LTC institutions promoted the use of those institutions, whereas that
      of general beds had a suppressive effect on such use, possibly due to social
      hospitalization. CONCLUSION: Our results suggest that the use of LTC institutions
      is accelerated by the age and disability level of users as well as the regional
      availability of such institutions and that an appropriate supply of LTC
      institutions could increase their use and potentially improve the efficiency of
      medical care.

PMID- 21843200
TI  - Comparison of the psychosocial quality of life in hemodialysis patients between
      the elderly and non-elderly using a visual analogue scale: the importance of
      appetite and depressive mood.
AB  - AIM: The number of hemodialysis (HD) patients is increasing along with their mean
      age in Japan. The assessment of their psychosocial status and quality of life
      (QOL) is therefore becoming more and more important along with laboratory data or
      comorbidities. METHODS: We examined the psychosocial status of 211 HD patients
      (72 elderly and 139 non-elderly) and compared the difference between elderly and
      non-elderly patients using a visual analogue scale (VAS). We then examined how
      QOL affected mortality rate in 3-year prospective follow up. We assessed 10 items
      of QOL: health condition, appetite, sleep, mood, memory, family relationships,
      friendship, economical status, life satisfaction in daily life, and happiness
      with qualified self-evaluating questionnaires along with laboratory data and
      comorbidities. Furthermore, we investigated the correlation between the scores of
      mood and geriatric depression scale (GDS)-15. RESULTS: There was no difference in
      VAS scores between elderly and non-elderly patients. Lower VAS scores for
      appetite and mood correlated with higher mortality in HD patients, especially in
      the non-elderly. VAS scores for mood correlated with GDS-15 in HD patients.
      CONCLUSIONS: More attention should be paid to appetite and the diagnosis and
      therapy of depressive mood to improve the prognosis of HD patients, especially
      for the non-elderly.

PMID- 21843201
TI  - Aggressive behavior in patients with dementia: correlates and management.
AB  - AIM: To consider the phenomenon of aggressive behavior perpetrated by people with
      dementia. METHODS: We searched electronic databases and key journals using the
      search terms: aggressive behavior; dementia; behavioral and psychological
      symptoms. RESULTS: Aggressive behavior (AB) is probably one of the principal
      problems in dementia. Aggression is linked to internal factors (depression,
      psychosis, pain) and external determinants (caregiver burden, social stimulation,
      quality of caregiver-patient relationship). It has been suggested that
      challenging behavior in people with dementia reflects their premorbid personality
      traits. CONCLUSION: Over the course of the illness AB occurs in 30 to 50% of
      patients and causes extreme stress for caregivers. Careful identification of
      target symptoms and their consequences, non-pharmacological approaches, and use
      of the least harmful medication for the shortest period of time should be the
      guiding principle of treatment.

PMID- 21843202
TI  - Distribution, characterization and genetic bases of erythromycin resistance in
      staphylococci and enterococci originating from livestock.
AB  - The occurrence of staphylococci and enterococci expressing increased resistance
      to erythromycin (ERY) and, in particular, to macrolide-lincosamide-streptogramin
      B (MLS(B) ) antibiotics was investigated in dairy cattle, pigs and turkeys. Three
      hundred rectal (cloacal) swabs of each animal species were examined. A total of
      120 and 71 staphylococci and enterococci, respectively, with increased resistance
      to ERY were identified. These were most frequent in turkeys (42.3% of positive
      animals), followed by pigs and dairy cattle (6.7% and 6.0% of positive animals,
      respectively). Similarly, MLS(B) -resistant isolates colonized predominantly
      turkeys (29.7% of animals), while their occurrence in pigs and dairy cattle was
      only sporadic (0.8% of animals). At least one of the erm genes encoding for
      MLS(B)  resistance was found in 56.7% and 69.0% of staphylococci and enterococci,
      respectively. The erm(C) gene prevailed in staphylococci while the erm(B) gene
      was predominant in enterococci. Macrolide efflux genes msr(A) and msr(C) were
      also frequent in staphylococci and enterococci, respectively. Macrolide
      inactivation gene mph(C) occurred mainly in staphylococci. In staphylococci,
      methicillin resistance was rarely detected (7.5% of isolates), but resistance to
      telithromycin (ketolides) was frequent in both staphylococci and enterococci
      (89.2% and 47.9% of isolates, respectively). This study showed that turkeys
      represent an important source of ERY (MLS(B) )-resistant cocci. In addition,
      resistance to ketolides was also frequent.

PMID- 21843203
TI  - A field block for breast cancer surgery: technical aspects and a pilot study.

PMID- 21843204
TI  - Effects of listening to music on pain intensity and pain distress after surgery:
      an intervention.
AB  - AIMS: To evaluate the effects of music listening on pain intensity and pain
      distress on the first and second postoperative days in abdominal surgery patients
      and the long-term effects of music on the third postoperative day. BACKGROUND:
      Music has been found to relieve pain intensity in surgery patients. There are
      only a few studies on music intervention in abdominal surgery. Music intervention
      studies assessing multidimensional pain such as pain intensity and pain distress
      are also scarce. DESIGN: Prospective clinical study with two parallel groups.
      METHODS: Patients undergoing elective abdominal surgery (n = 168) were divided
      into either a music group (n = 83) or a control group (n = 85). Patients assessed
      pain intensity and pain distress in bed rest, during deep breathing and in
      shifting position once in the evening of the operation day and on the first and
      second postoperative days in the morning, at noon and in the evening. On the
      third postoperative day, the patients assessed their pain intensity and pain
      distress only once. RESULTS: In the music group, the patients' pain intensity and
      pain distress in bed rest, during deep breathing and in shifting position were
      significantly lower on the second postoperative day compared with control group
      of patients. On the third postoperative day, when long-term effects of music on
      pain intensity and pain distress were assessed, there were no significant
      differences between music and control groups. CONCLUSION: This study demonstrates
      that the use of music alleviates pain intensity and pain distress in bed rest,
      during deep breathing and in shifting position after abdominal surgery on the
      second postoperative day. Music intervention is safe, inexpensive and easily used
      to improve the healing environment for abdominal surgery patients. RELEVANCE TO
      CLINICAL PRACTICE: Music intervention should be offered as an adjunct alternative
      to pharmacological pain relief after abdominal surgery in nursing practice.

PMID- 21843205
TI  - Protective effects of a magnesium magnetic isotope (Mg25)-exchanging nanoparticle
      (25MgPMC16 ) on mitochondrial functional disorders in esmolol-induced cardiac
      arrest in rats.
AB  - In cardiac surgery, agents are needed to produce temporary cardiac arrest
      (cardioplegia). One of these agents is esmolol (ESM) which is a short-acting
      selective beta-1 adrenergic receptor antagonist and its overdose causes diastolic
      ventricular arrest. The (25) MgPMC(16) (porphyrin adducts of cyclohexil fullerene
      C60) is known as a nanoparticle which has a cardioprotective effect when the
      heart is subjected to stressful conditions. In this study, we aimed to confirm
      the deleterious effects of ESM overdose on cardiac mitochondria and identify any
      protective effects of (25) MgPMC(16) in male Wistar rats. Esmolol 100 mg kg(-1)
      (LD50 = 71 mg kg(-1) ) was injected intravenously (i.v.) into tail vein to induce
      cardiac arrest. This dose was obtained from an ESM dose-response curve which
      induces at least 80% arrest in rats. (25) MgPMC(16) at three different doses (45,
      90 and 224 mg kg(-1) ) was injected i.v. as pretreatment, eight hours before ESM
      injection. (25) MgCl(2) or (24) MgPMC(16) were used as controls. Following
      cardiac arrest, the heart was removed and the mitochondria extracted.
      Mitochondrial viability and the adenosine 5'-diphosphate sodium salt
      hydrate/Adenosine 5'-triphosphate disodium salt hydrate (ADP/ATP) ratio were
      measured as biomarkers of mitochondrial function. Results indicate that (25)
      MgPMC(16) caused a significant increase in mitochondrial viability and decrease
      in ADP/ATP ratio. No significant changes were seen with (24) MgPMC(16) or (25)
      MgCl(2) . It is concluded that cardiac arrest induced by ESM overdose leads to a
      significant decrease in mitochondrial viability and their ATP levels, whereas
      pretreatment by (25) MgPMC(16) can protect mitochondria by increasing ATP level
      through liberation of Mg into cells and the improvement of hypoxia.

PMID- 21843207
TI  - A qualitative study exploring the nurse telephone follow-up of patients returning
      home with a colostomy.
AB  - AIM: The aim of this study was to explore and describe the content of telephone
      intervention conversations conducted by an enterostomal nurse with patients
      discharged home with a colostomy. BACKGROUND: People discharged home with a new
      colostomy often encounter stoma-related difficulties. Postdischarge care with
      telephone follow-up by an enterostomal nurse is a helpful way to provide support
      for patients and ensure continuity of care. There is a paucity of studies
      reporting the content of telephone follow-up of colostomy patients. Information
      on the content of such follow-up is important in helping to formulate telephone
      call protocols that can help these patients. DESIGN: A qualitative exploratory
      study conducted in a university-based cancer centre in China. METHODS: The
      contents of 25 intervention phone calls to colostomy patients from January-August
      2009 were subject to qualitative content analysis. RESULTS: Five themes emerged
      from the qualitative content analysis: 'education for stoma care', 'access to
      stoma care', 'encouraging stoma self-care', 'resuming normal living' and 'general
      postoperative problems'. CONCLUSIONS: Colostomy patients experienced stoma
      related problems and difficulties after discharge, most of which could be
      effectively managed via telephone follow-up by an enterostomal nurse. The
      telephone follow-up satisfied patients' need for information and facilitated
      their adjustment to the permanent stoma. The findings suggested that patients had
      unmet needs after discharge and needed follow-up on returning home. RELEVANCE TO
      CLINICAL PRACTICE: This study provides important information to guide practice
      and education. The themes extracted from the qualitative content analysis provide
      a useful framework to guide the nurse in discussing care with the stoma patients
      and ensuring patients' adjustment to the permanent stoma. Further work can be
      done using this framework to develop protocols as standards of care and education
      materials when educating nurse specialists in stoma care.

PMID- 21843206
TI  - Biofilm growth alters regulation of conjugation by a bacterial pheromone.
AB  - Conjugation is an important mode of horizontal gene transfer in bacteria,
      enhancing the spread of antibiotic resistance. In clinical settings, biofilms are
      likely locations for antibiotic resistance transfer events involving nosocomial
      pathogens such as Enterococcus faecalis. Here we demonstrate that growth in
      biofilms alters the induction of conjugation by a sex pheromone in E. faecalis.
      Mathematical modelling suggested that a higher plasmid copy number in biofilm
      cells would enhance a switch-like behaviour in the pheromone response of donor
      cells with a delayed, but increased response to the mating signal. Alterations in
      plasmid copy number, and a bimodal response to induction of conjugation in
      populations of plasmid-containing donor cells were both observed in biofilms,
      consistent with the predictions of the model. The pheromone system may have
      evolved such that donor cells in biofilms are only induced to transfer when they
      are in extremely close proximity to potential recipients in the biofilm
      community. These results may have important implications for development of
      chemotherapeutic agents to block resistance transfer and treat biofilm-related
      clinical infections.

PMID- 21843208
TI  - Outdoor air pollution and respiratory health in Asia.
AB  - With the rapid economic development occurring in the last decade in many
      countries of Asia, the level of air pollution has increased from both industrial
      and motor vehicle emissions. Compared with Europe and North America, the
      potential health effects of this increasing air pollution in Asia remain largely
      unmeasured. Recent data published by the Health Effects Institute from some major
      cities in India and China reveal that a 10 ug/m(3)  increase in PM(10)  was
      associated with an increase in mortality of 0.6% in daily all-natural cause
      mortality, with higher risks being found at extremes of high temperatures and in
      the lowest economically advantaged population. Other Asian studies have confirmed
      the link between hospital admissions for the worsening of COPD and the increase
      in asthma prevalence to levels of outdoor air pollutants. Although potential
      health effects appear to be similar to already-published Western data, it is
      important that further studies be carried out in Asia that will inform the public
      and the authorities of the necessity to curb levels of outdoor air pollutants to
      acceptable levels.

PMID- 21843209
TI  - Interproximal cervical lesions caused by incorrect flossing technique.
AB  - This case report describes an interproximal cervical lesion caused by the
      incorrect use of dental floss. A 58-year-old man who was asymptomatic, presented
      with unusual notch-like cervical lesions. After clinical and radiographical
      examinations, it was concluded that the aetiology of these lesions was an
      incorrect flossing technique. The treatment plan included extraction of maxillary
      3rd molars and re-education of the patient in oral hygiene technique. CONCLUSION:
      These lesions are irreversible and often go undiagnosed; therefore, it is
      important for the clinician to be familiar with the clinical presentation and
      aetiology.

PMID- 21843210
TI  - Histochemical detection of glycoconjugates in the inner perivitelline layer of
      Japanese quail (Coturnix japonica).
AB  - The avian inner perivitelline layer (IPVL), a homologous structure to the
      mammalian zona pellucida, is deposited between the granulosa cells and the oocyte
      cell membrane during folliculogenesis. In this glycohistochemical study, a panel
      of fluorescein isothiocyanate (FITC)-labelled lectins was used to characterise
      and localise the oligosaccharide sequences of the IPVL glycoproteins at different
      stages of follicular development in the quail ovary. Deacetylation and sialidase
      digestion were also performed prior to lectin cytochemistry. Contrary to mammals,
      where the topographical distribution of these carbohydrates is not uniformly
      distributed throughout the zona pellucida, indicating the regionalisation of
      oligosaccharide chains, our results demonstrated a homogenous lectin staining of
      the comparatively thin IPVL. We also found variations in the presence and
      distribution of the carbohydrate residues in the IPVL during different stages of
      follicular growth. The IPVL of pre-vitelline follicles distinctly stains with
      WGA, sWGA and SBA, demonstrating the presence of D-GlcNAc, Neu5Ac and alpha-D
      GalNac in the glycoproteins of the forming IPVL. No staining was found with ConA
      (specific for alpha-D-Man, alpha-D-Glc), LCA (alpha-D-Man, alpha-D-Glc), PNA
      (beta-D-Gal-(1-3)-D-GalNAc, VAA (Gal), DBA (alpha-D-GalNAc(1-3)-GalNAc and UEA-I
      (alpha-L-Fuc). With continuing follicular growth of the oocyte and the follicle,
      this staining pattern changed. LCA and PNA-staining in the IPVL became distinctly
      positive. As the IPVL of immature oocytes distinctly stains with WGA/sWGA-FITC,
      but spermatozoa do not bind to immature zona, it appears questionable that
      carbohydrate residues detected by WGA/sWGA play a major role in sperm-IPVL
      binding, as suggested in previous investigations.

PMID- 21843211
TI  - Perceived family health in persons with prostate cancer and their family members.
AB  - AIMS AND OBJECTIVES: To describe perceived family health in persons with prostate
      cancer and their family members. An additional purpose was to describe the
      associations between the background variables of persons with prostate cancer and
      their family members and perceived family health. BACKGROUND: Prostate cancer in
      one family member affects the health of the whole family. It is important to
      study perceived family health in families of persons with prostate cancer and
      associated factors. DESIGN: A cross-sectional study. METHOD: Data were collected
      using the Family Functioning, Health and Social Support (FAFHES) scale, modified
      for use in this study. Questionnaires were distributed to 100 persons with
      prostate cancer treated with surgery or radiation therapy and 100 family members
      at one Finnish university hospital in April-October 2009. Responses were received
      from 76 persons and 71 family members, a response rate of 74%. RESULTS: Persons
      with prostate cancer and family members rated family health good despite prostate
      cancer. Family members reported higher levels of illness-related ill-being than
      persons with prostate cancer. Family health was associated with the person's age,
      basic education, employment status, number of family member's visits to the
      hospitalised patient, first symptom of prostate cancer and previous
      hospitalisations were associated with. Family health was associated with the
      family member's basic and vocational education. CONCLUSIONS: The results show
      that nursing care should pay attention to family members of persons with prostate
      cancer and that support to them should be a natural part of a good care of
      persons with prostate cancer. RELEVANCE TO CLINICAL PRACTICE: The quality of
      prostate cancer care should be improved to provide more individualised and family
      focussed services.

PMID- 21843214
TI  - Getting the evidence straight in emergency diagnostics.
AB  - The interpretation and optimal application of the myriad of diagnostic modalities
      at the emergency physician's (EP's) disposal is a core challenge of clinical
      practice. Connecting the wealth of scientific literature that informs our
      understanding of test performance, including elements of the history and the
      physical examination, is a daunting task. Translating this knowledge into
      improved patient outcomes requires two fundamentals; the first involves getting
      the evidence "straight" through systematic approaches that highlight quality work
      and methods for getting evidence to the point of need. This commentary discusses
      the potential impact of the first installment in the "evidence-based diagnostics"
      series of the journal, highlighting how this work complements existing resources
      of evidence-based medicine. In addition, a vision is presented for how the
      insight from this series can achieve integration into the clinical and academic
      mission of emergency medicine.

PMID- 21843215
TI  - Ketamine/propofol versus midazolam/fentanyl for procedural sedation and analgesia
      in the emergency department: a randomized, prospective, double-blind trial.
AB  - OBJECTIVES: The authors performed a prospective, double-blinded, randomized trial
      with emergency department (ED) patients requiring procedural sedation and
      analgesia (PSA) for repair of deep traumatic lacerations and reduction of bone
      fractures, to compare the ketamine/propofol (ketofol) combination with the
      midazolam/fentanyl (MF) combination. METHODS: Sixty-two patients scheduled for
      PSA who presented between January 2009 and June 2009 were enrolled prospectively.
      Thirty-one were randomly assigned to the ketofol group, and 31 were assigned to
      the MF group. RESULTS: The median starting doses were 0.75 mg/kg of both ketamine
      and propofol (interquartile range [IQR] = 0.75 to 1.5 mg/kg), 0.04 mg/kg
      midazolam (IQR = 0.04 to 0.06 mg/kg), and 2 MUg/kg fentanyl (IQR = 2 to 3
      MUg/kg). There were no significant differences in sedation time between the
      groups. There were no differences in physician satisfaction (p = 0.065).
      Perceived pain in the ketofol group, as measured by the Visual Analog Scale
      (VAS), was significantly lower than in the MF group (median ketofol = 0, IQR = 0
      1 vs. median MF = 3, IQR = 1-6; p < 0.001). Only one patient in each group
      required bag-mask ventilation, and neither of them were intubated. CONCLUSIONS:
      The ketamine/propofol combination provides adequate sedation and analgesia for
      painful procedures and appears to be a safe and useful technique in the ED.

PMID- 21843213
TI  - Evidence-based diagnostics: adult septic arthritis.
AB  - BACKGROUND: Acutely swollen or painful joints are common complaints in the
      emergency department (ED). Septic arthritis in adults is a challenging diagnosis,
      but prompt differentiation of a bacterial etiology is crucial to minimize
      morbidity and mortality. OBJECTIVES: The objective was to perform a systematic
      review describing the diagnostic characteristics of history, physical
      examination, and bedside laboratory tests for nongonococcal septic arthritis. A
      secondary objective was to quantify test and treatment thresholds using derived
      estimates of sensitivity and specificity, as well as best-evidence diagnostic and
      treatment risks and anticipated benefits from appropriate therapy. METHODS: Two
      electronic search engines (PUBMED and EMBASE) were used in conjunction with a
      selected bibliography and scientific abstract hand search. Inclusion criteria
      included adult trials of patients presenting with monoarticular complaints if
      they reported sufficient detail to reconstruct partial or complete 2 * 2
      contingency tables for experimental diagnostic test characteristics using an
      acceptable criterion standard. Evidence was rated by two investigators using the
      Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than
      one similarly designed trial existed for a diagnostic test, meta-analysis was
      conducted using a random effects model. Interval likelihood ratios (LRs) were
      computed when possible. To illustrate one method to quantify theoretical points
      in the probability of disease whereby clinicians might cease testing altogether
      and either withhold treatment (test threshold) or initiate definitive therapy in
      lieu of further diagnostics (treatment threshold), an interactive spreadsheet was
      designed and sample calculations were provided based on research estimates of
      diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits. RESULTS: The
      prevalence of nongonococcal septic arthritis in ED patients with a single acutely
      painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%).
      With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or
      skin infection overlying a prosthetic joint (+LR = 15.0), history, physical
      examination, and serum tests do not significantly alter posttest probability.
      Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte
      sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely.
      The interval LR for synovial white blood cell (sWBC) counts of 0 * 10(9)-25 *
      10(9)/L was 0.33; for 25 * 10(9)-50 * 10(9)/L, 1.06; for 50 * 10(9)-100 *
      10(9)/L, 3.59; and exceeding 100 * 10(9)/L, infinity. Synovial lactate may be
      useful to rule in or rule out the diagnosis of septic arthritis with a +LR
      ranging from 2.4 to infinity, and negative likelihood ratio (-LR) ranging from 0
      to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the
      causative organism within 3 hours. Based on 56% sensitivity and 90% specificity
      for sWBC counts of >50 * 10(9)/L in conjunction with best-evidence estimates for
      diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis
      test threshold is 5%, with a treatment threshold of 39%. CONCLUSIONS: Recent
      joint surgery or cellulitis overlying a prosthetic hip or knee were the only
      findings on history or physical examination that significantly alter the
      probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 *
      10(9)/L) can increase, but not decrease, the probability of septic arthritis.
      Future ED-based diagnostic trials are needed to evaluate the role of clinical
      gestalt and the efficacy of nontraditional synovial markers such as lactate.

PMID- 21843216
TI  - Assessing bladder volumes in young children prior to instrumentation: accuracy of
      an automated ultrasound device compared to real-time ultrasound.
AB  - OBJECTIVES: Automated bladder ultrasound (ABUS) devices are portable and designed
      to provide automated measurement of bladder volume. They are simple and require
      minimal training compared to conventional real-time ultrasound (RTUS). Their most
      common application in the acute pediatric setting is to assess bladder volumes
      prior to performing invasive urine collection such as suprapubic aspiration (SPA)
      in children younger than 2 years of age. However, data on ABUS in young children
      are limited. The aim of this study was to assess the repeatability and accuracy
      of one type of ABUS, the BladderScan, in measuring of bladder volume in children
      aged 0 to 24 months when compared with RTUS. METHODS: Healthy children aged 24
      months and younger were scanned twice, 1 hour apart, using ABUS and RTUS. ABUS
      readings were performed by two senior pediatric emergency physicians who both
      completed three readings for each child. The measurements were repeated using a
      second ABUS machine in case of machine variability. RTUS measurements were
      performed by a pediatric sonographer who was blinded to the ABUS results. ABUS
      and RTUS measurements were compared by Bland-Altman analysis to determine the
      repeatability coefficient (repeatability) and the limits of clinical agreement
      (accuracy). RESULTS: Bladder volume measurements were performed on 61 children
      aged 0 to 24 months (31 males; mean +/- SD = age 11 +/- 6.2 months; range = 0 to
      24 months) using both the ABUS and the RTUS. There was wide variation between
      ABUS and RTUS measurements. The repeatability coefficient within ABUS readings
      was 20 mL. By Bland-Altman analysis, the 95% limits of agreement between ABUS and
      RTUS were -31 to +19 mL. ABUS also detected no values between 0 and 10 mL.
      CONCLUSIONS: This study showed poor repeatability and accuracy in bladder volume
      measurements using BladderScan ABUS when compared to RTUS. The ABUS method does
      not appear to be a reliable method for assessing bladder volumes in children aged
      0 to 24 months prior to bladder instrumentation.

PMID- 21843217
TI  - Comparison of an informally structured triage system, the emergency severity
      index, and the manchester triage system to distinguish patient priority in the
      emergency department.
AB  - OBJECTIVES: The objective was to compare the validity of an existing informally
      structured triage system with the Emergency Severity Index (ESI) and the
      Manchester Triage System (MTS). METHODS: A total of 900 patients were
      prospectively triaged by six trained triage nurses using the three systems.
      Triage ratings of 421 (48%) patients treated only by emergency department (ED)
      physicians were compared with a reference standard determined by an expert panel.
      The percentage of undertriage, the sensitivity, and the specificity for each
      urgency level were calculated. The relationship between urgency level, resource
      use, hospitalization, and length of stay (LOS) in the 900 triaged patients was
      determined. RESULTS: The percentage of undertriage using the ESI (86 of 421; 20%)
      was significantly higher than in the MTS (48 of 421; 11%). When combining urgency
      levels 4 and 5, the percentage of undertriage was 8% for the informally
      structured system (ISS), 14% for the ESI, and 11% for the MTS. In all three
      systems, sensitivity for all urgency levels was low, but specificity for levels 1
      and 2 was high (>92%). Sensitivity and specificity were significantly different
      between ESI and MTS only in urgency level 4. In all 900 patients triaged, urgency
      levels across all systems were associated with significantly increased resource
      use, hospitalization rate, and LOS. CONCLUSIONS: All three triage systems appear
      to be equally valid. Although the ESI showed the highest percentage of
      undertriage and the ISS the lowest, it seems preferable to use a verifiable,
      formally structured triage system.

PMID- 21843218
TI  - High plasma lactate levels are associated with increased risk of in-hospital
      mortality in patients with pulmonary embolism.
AB  - OBJECTIVES: The objective was to investigate the prognostic value of plasma
      lactate in patients with acute pulmonary embolism (PE). METHODS: This was a
      retrospective study at the emergency department (ED) of a third-level teaching
      hospital. The authors considered consecutive patients with a diagnosis of PE
      established by lung scan or spiral computed tomography (CT) and confirmed by
      pulmonary angiography if necessary. Only patients for whom plasma lactate levels
      had been tested within 6 hours from presentation to the ED were included. Primary
      outcome was in-hospital death due to any cause; secondary outcome was mortality
      related to PE. RESULTS: From September 1997 to June 2006, a total of 384 patients
      were diagnosed with PE in the ED. Of these patients, 287 had registered plasma
      lactate levels and were included in this analysis. Included patients had a mean
      age of 70 (SD +/- 15 years, range = 18 to 100 years), 163 (57%) were female, 26
      (9%) showed systolic blood pressure lower than 100 mm Hg at presentation, and 160
      (56%) had echocardiographic evidence of right ventricular dysfunction (RVD).
      Twenty patients died during their hospital stay (7%). Plasma lactate levels >= 2
      mmol/L were associated with in-hospital mortality from all causes (odds ratio
      [OR] = 4.60, 95% confidence interval [CI] = 1.57 to 13.53) and with PE-related
      mortality (OR = 4.94, 95% CI = 1.38 to 17.63), independent of hypotension or RVD
      at presentation. CONCLUSIONS: High plasma lactate was associated with increased
      in-hospital mortality in this sample of patients with acute PE.

PMID- 21843219
TI  - A population-based study of the association between socioeconomic status and
      emergency department utilization in Ontario, Canada.
AB  - OBJECTIVES: The relative effects of socioeconomic status (SES) and health status
      on emergency department (ED) utilization are controversial. The authors examined
      this in a setting with universal health coverage. METHODS: For Ontario
      participants age 20-74 years, Canadian Community Health Survey 2000 to 2001
      responses were linked to Ontario Health Insurance Plan (OHIP) physician
      utilization data for 1999 to 2001 and the National Ambulatory Care Reporting
      System (NACRS) for ED utilization in 2002. SES was defined primarily according to
      high school completion and secondarily according to income. The primary outcome
      was less urgent ED visit, defined as Canadian Triage and Acuity Scale (CTAS) 4 or
      5 and not admitted to hospital. RESULTS: The weighted sample was 9,323,217.
      Overall, 31.4% of the sample used an Ontario ED in 2002. The majority of visits
      (59.1%) were classified as less urgent. Fair or poor self-perceived health was
      the largest predictor of ED use, regardless of visit urgency. Respondents with
      low education were more likely to have both less urgent visits (odds ratio [OR] =
      1.65, 95% confidence interval [CI] = 1.35 to 1.94) and more urgent visits (OR =
      1.39, 95% CI = 1.09 to 1.68) after controlling for age, sex, income, self
      perceived health, urban or rural location, regular doctor, and non-ED physician
      visits. Education was not associated with having less urgent versus more urgent
      visits (OR = 0.92, 95% CI = 0.68 to 1.14). CONCLUSIONS: In a setting with
      universal health insurance, worse health status is the largest predictor of ED
      utilization, but low SES is independently associated with increased use of the
      ED, regardless of visit urgency. This study lends support to findings in other
      health systems that those using EDs are more ill and more disadvantaged.

PMID- 21843220
TI  - Predicting hospital admissions at emergency department triage using routine
      administrative data.
AB  - OBJECTIVES: To be able to predict, at the time of triage, whether a need for
      hospital admission exists for emergency department (ED) patients may constitute
      useful information that could contribute to systemwide hospital changes designed
      to improve ED throughput. The objective of this study was to develop and validate
      a predictive model to assess whether a patient is likely to require inpatient
      admission at the time of ED triage, using routine hospital administrative data.
      METHODS: Data collected at the time of triage by nurses from patients who visited
      the ED in 2007 and 2008 were extracted from hospital administrative databases.
      Variables included were demographics (age, sex, and ethnic group), ED visit or
      hospital admission in the preceding 3 months, arrival mode, patient acuity
      category (PAC) of the ED visit, and coexisting chronic diseases (diabetes,
      hypertension, and dyslipidemia). Chi-square tests were used to study the
      association between the selected possible risk factors and the need for hospital
      admission. Logistic regression was applied to develop the prediction model. Data
      were split for derivation (60%) and validation (40%). Receiver operating
      characteristic curves and goodness-of-fit tests were applied to the validation
      data set to evaluate the model. RESULTS: Of 317,581 ED patient visits, 30.2%
      resulted in immediate hospital admission. In the developed predictive model, age,
      PAC status, and arrival mode were most predictive of the need for immediate
      hospital inpatient admission. The c-statistic of the receiver operating
      characteristic (ROC) curve was 0.849 (95% confidence interval [CI] = 0.847 to
      0.851). The goodness-of-fit test showed that the predicted patients' admission
      risks fit the patients' actual admission status well. CONCLUSIONS: A model for
      predicting the risk of immediate hospital admission at triage for all-cause ED
      patients was developed and validated using routinely collected hospital data.
      Early prediction of the need for hospital admission at the time of triage may
      help identify patients deserving of early admission planning and resource
      allocation and thus potentially reduce ED overcrowding.

PMID- 21843221
TI  - Copeptin and peroxiredoxin-4 independently predict mortality in patients with
      nonspecific complaints presenting to the emergency department.
AB  - OBJECTIVES: Patients presenting to emergency departments (ED) with nonspecific
      complaints (NSCs) such as "not feeling well,""feeling weak,""being
      tired,""general deterioration," or other similar chief complaints that do not
      have a readily identifiable probable etiology are a common patient group at risk
      for adverse outcomes. Certain biomarkers, which have not yet been tested for
      prognostic value when applied to ED patients with NSCs, have emerged as useful
      tools for predicting prognosis in patients with a variety of diseases. This study
      tested the hypothesis that two of these novel markers, copeptin (a C-terminal
      portion of provasopressin) and/or peroxiredoxin-4 (Prx4), an enzyme that degrades
      hydrogen peroxide, singly or together are helpful in predicting death in the near
      term among patients presenting to the ED with NSCs. METHODS: The Basel Non
      specific Complaints (BANC) study is a delayed type cross-sectional diagnostic
      study with a prospective 30-day follow-up. ED patients with NSCs were
      consecutively enrolled. Patients with vital parameters out of the normal range
      were excluded. The primary endpoint of this study was the predictive value of
      copeptin and Prx4 for 30-day mortality in patients with NSCs. Measurement of both
      copeptin and Prx4 was performed in serum samples with sandwich immunoluminometric
      assays. RESULTS: On follow-up at 30 days after ED presentation, 28 of 438
      patients with NSC had died. Copeptin and Prx4 concentrations were significantly
      higher in nonsurvivors than in survivors (Kruskal-Wallis test, p = 0.0001 and p <
      0.0001, respectively). In univariate models, Prx4 (likelihood ratio [LR] chi(2) =
      22.24, p < 0.00001, concordance index [C-index] = 0.749) and copeptin (LR chi(2)
      = 16.98, p = 0.00004, C-index = 0.724) were both predictive of 30-day mortality,
      and elevated levels were associated with an increased mortality. The bivariable
      model, which included both Prx4 and copeptin (LR chi(2) = 28.22, p < 0.00001, C
      index = 0.783), allows a significantly better prediction than the univariate Prx4
      (p = 0.00025) and copeptin models (p = 0.00099), respectively. Both biomarkers
      provided independent and additional information to clinical risk scores (Katz
      Activities of Daily Living [ADL] and Charlson Comorbidity Index [CCI], all p <
      0.0005). CONCLUSIONS: Copeptin and Prx4 are new prognostic markers in patients
      presenting to the ED with NSCs. Copeptin and Prx4 might be valuable tools for
      risk stratification and decision-making in this patient group.

PMID- 21843222
TI  - Randomized crossover trial comparing physical strain on advanced life support
      providers during transportation using real-time automated feedback.
AB  - BACKGROUND: Feedback devices provide verbal and visual real-time information on
      cardiopulmonary resuscitation (CPR) quality. Feedback devices can improve the
      quality of CPR during transportation. It remains unclear if feedback has an
      effect on the physical strain felt by providers during ongoing CPR. OBJECTIVES:
      The objective was to assess the influence of real-time automated feedback on
      physical strain of rescuers during ongoing chest compressions in different means
      of transportation. METHODS: The study was a randomized crossover trial comparing
      physical strain on advanced life support (ALS) providers during chest
      compressions using real-time automated feedback in different transport
      environments: 1) a moving ambulance and 2) a flying helicopter. The authors
      measured objective and subjective measures of physical strain and calculated the
      difference in the rate pressure product (RPP) after 8 minutes of external chest
      compressions. RESULTS: There was no difference in the RPP (mean intraindividual
      difference = 21; 95% confidence interval [CI] = -1,438 to 1,480; p = 0.98)
      between using the feedback device versus no feedback. There was no significant
      interaction of vehicle type on the effect of feedback on the RPP. Feedback
      resulted in a significant mean perceived exertion reduction of a Borg scale score
      by 0.89 points (95% CI = 0.42 to 1.35; p < 0.001). For systolic and diastolic
      blood pressure, for serum lactate concentrations, and for the modified Nine Hole
      Peg Test (NHPT; measurement of fine motor skills), we found no statistically
      significant differences. CONCLUSIONS: Feedback devices for CPR during
      transportation do not have an effect on objective components of physical strain,
      but decrease perceived exertion in experienced rescuers in an experimental
      setting.

PMID- 21843223
TI  - Africa's first emergency medicine training program at the University of Cape
      Town/Stellenbosch University: history, progress, and lessons learned.
AB  - Africa's first residency training program in emergency medicine (EM) was
      established at the University of Cape Town (UCT)/Stellenbosch University (SUN) in
      2004. There have since been four classes for a total of 29 graduates from this
      program who are practicing, teaching, and leading EM. This article describes the
      structure of the program and discusses the history and major drivers behind its
      founding. We report major changes, cite ongoing challenges, and discuss lessons
      learned from the program's first 7 years that may help advise other nascent
      training programs in developing countries.

PMID- 21843224
TI  - Quality and consistency of guidelines for the management of mild traumatic brain
      injury in the emergency department.
AB  - OBJECTIVES: The objective was to provide an overview of the recommendations and
      quality of evidence-based clinical practice guidelines (CPGs) for the emergency
      management of mild traumatic brain injury (mTBI), with a view to informing best
      practice and improving the consistency of recommendations. METHODS: Electronic
      searches of health databases (MEDLINE, EMBASE, The Cochrane Library, PsycINFO),
      CPG clearinghouse websites, CPG developer websites, and Internet search engines
      up to January 2010 were conducted. CPGs were included if 1) they were published
      in English and freely accessible, 2) their scope included the management of mTBI
      in the emergency department (ED), 3) the date of last search was within the past
      10 years (2000 onward), 4) systematic methods were used to search for evidence,
      and 5) there was an explicit link between the recommendations and the supporting
      evidence. Four authors independently assessed the quality of the included CPGs
      using the Appraisal of Guidelines, Research and Evaluation (AGREE) Instrument.
      The authors extracted and categorized recommendations according to initial
      clinical assessment, imaging, management, observation, discharge planning, and
      patient information and follow-up. RESULTS: The search identified 18 potential
      CPGs, of which six met the inclusion criteria. The included CPGs varied in scope,
      target population, size, and guideline development processes. Four CPGs were
      assessed as "strongly recommended." The majority of CPGs did not provide
      information about the level of stakeholder involvement (mean AGREE standardized
      domain score = 57%, range = 25% to 81%), nor did they address the
      organizational/cost implications of applying the recommendations or provide
      criteria for monitoring and review of recommendations in practice (mean AGREE
      standardized domain score = 46.6%, range = 19% to 94%). Recommendations were
      mostly consistent in terms of the use of the Glasgow Coma Scale (GCS) score
      (adult and pediatric) to assess the level of consciousness, initial assessment
      criteria, the use of computed tomography (CT) scanning as imaging investigation
      of choice, and the provision of patient information. The CPGs defined mTBI in a
      variety of ways and described different rules to determine the need for CT
      scanning and therefore used different criteria to identify high-risk patients.
      CONCLUSIONS: Higher-quality CPGs for mTBI are consistent in their recommendations
      about assessment, imaging, and provision of patient information. There is not,
      however, an agreed definition of mTBI, and the quality of future CPGs could be
      improved with better reporting of stakeholder involvement, procedures for
      updating, and greater consideration of the applicability of the recommendations
      (cost implications, monitoring procedures). Nevertheless, guideline developers
      may benefit from adapting existing CPGs to their local context rather than
      investing in developing CPGs de novo.

PMID- 21843225
TI  - Pan-Asian Resuscitation Outcomes Study (PAROS): rationale, methodology, and
      implementation.
AB  - Disease-based registries can form the basis of comparative research to improve
      and inform policy for optimizing outcomes, for example, in out-of-hospital
      cardiac arrest (OHCA). Such registries are often lacking in resource-limited
      countries and settings. Anecdotally, survival rates for OHCA in Asia are low
      compared to those in North America or Europe, and a regional registry is needed.
      The Pan-Asian Resuscitation Outcomes Study (PAROS) network of hospitals was
      established in 2009 as an international, multicenter, prospective registry of
      OHCA across the Asia-Pacific region, to date representing a population base of 89
      million in nine countries. The network's goal is to provide benchmarking against
      established registries and to generate best practice protocols for Asian
      emergency medical services (EMS) systems, to impact community awareness of
      prehospital emergency care, and ultimately to improve OHCA survival. Data are
      collected from emergency dispatch, ambulance providers, emergency departments,
      and in-hospital collaborators using standard protocols. To date (March 2011),
      there are a total of 9,302 patients in the database. The authors expect to
      achieve a sample size of 13,500 cases over the next 2 years of data collection.
      The PAROS network is an example of a low-cost, self-funded model of an Asia
      Pacific collaborative research network with potential for international
      comparisons to inform OHCA policies and practices. The model can be applied
      across similar resource-limited settings.

PMID- 21843226
TI  - The evolution of academic performance in emergency medicine journals: viewpoint
      from 2000 to 2009 journal citation reports.
AB  - OBJECTIVES: Emergency medicine (EM) is a young but rapidly growing field. An
      evaluation of academic performance and the growing impact of EM journals would
      help to elucidate the increase in the number of EM scientific studies. The
      authors used the Journal Citation Reports (JCR) database to investigate the
      scientific achievements of EM journals in the past 10 years. METHODS: This was a
      literature review study. All data were collected from the JCR database. Journals
      listed in the EM category from 2000 to 2009 were included. Eleven categories that
      were considered most closely related to EM by a consensus of the authors were
      chosen for comparison, including cardiac and cardiovascular systems, clinical
      neurology, critical care medicine, gastroenterology and hepatology, infectious
      diseases, general and internal medicine, pediatrics, respiratory system, surgery,
      toxicology, and urology and nephrology. Data on journals in the EM category were
      collected, including journal title, language, journal country or territory,
      impact factor for each year, total number of EM journals for each year, and the
      EM category aggregate impact factor (available from 2003 to 2009). The variables
      in the comparison group included the number of journals in each of the 11
      clinical medicine categories from 2000 to 2009 and the aggregate impact factors
      for 2003 to 2009. The category aggregate impact factor and journal impact factor
      were adopted as representative of category and journal academic performance.
      Linear regression was used to assess the trend of aggregate impact factor and
      journal impact factor. The slope (beta) of the linear regression was used to
      represent the evolution of performance. The relationship between the 2000 EM
      journal impact factor and the impact factor trend of EM journals between 2000 and
      2009 was measured by Pearson correlation coefficient to evaluate the evolution
      difference between journals with different initial impact factors. RESULTS: In
      2000, all 12 EM journals were published in the United States or Europe, and the
      language of all was English. In 2009, 10% (2/19) of the journals originated from
      outside North America and Europe, and 16% (3/19) were non-English-language
      journals. The number of EM journals increased 58% from 2000 to 2009, twice the
      increase in the total number of JCR-listed journals, and rank first in the rate
      of journal number increase among categories of clinical medicine. The impact
      factor of all EM journals showed an increasingly positive trend since 2000. The
      impact factor increased faster for high impact factor EM journals than for low
      impact-factor EM journals. CONCLUSIONS: An increasing number of international EM
      journals have appeared over the past 10 years. Every EM journal exhibited a
      positive impact factor trend, but the gap between EM journals' impact factors has
      widened in the past 10 years.

PMID- 21843227
TI  - The Institute of Medicine (IOM) report of 2011 and the future of academic
      dentistry.

PMID- 21843229
TI  - Modified complete-arch impression technique for facilitating esthetic and
      biomechanical precision in complete-arch rehabilitation.
AB  - Treating complex cases is clinically and technically challenging, yet highly
      rewarding to both patient and clinician when successfully completed. Precision in
      the fit of the restorations, the definitive occlusal scheme, and the esthetic
      result are the key elements to long-term success. Clinicians should aim to
      achieve the same level of precision when treating these cases as they do when
      treating simple cases; however, with the numerous stages and increased complexity
      involved comes the potential for errors to compound and magnify as treatment
      progresses. Areas particularly prone to difficulties are the making of a complete
      arch impression and the ability to maintain patient comfort and eliminate
      unwanted dental emergencies throughout the time-consuming treatment. This report
      illustrates the techniques and concepts used to achieve esthetic and
      biomechanical precision when treating complex cases. Specific emphasis is placed
      on the importance of an accurate complete-arch impression technique, the detail
      of which is described in the article.

PMID- 21843228
TI  - In vitro study of fracture load and fracture pattern of ceramic crowns: a finite
      element and fractography analysis.
AB  - PURPOSE: This in vitro study investigated the null hypothesis that metal-free
      crowns induce fracture loads and mechanical behavior similar to metal ceramic
      systems and to study the fracture pattern of ceramic crowns under compressive
      loads using finite element and fractography analyses. MATERIALS AND METHODS: Six
      groups (n = 8) with crowns from different systems were compared: conventional
      metal ceramic (Noritake) (CMC); modified metal ceramic (Noritake) (MMC); lithium
      disilicate-reinforced ceramic (IPS Empress II) (EMP); leucite-reinforced ceramic
      (Cergogold) (CERG); leucite fluoride-apatite reinforced ceramic (IPS d.Sign)
      (SIGN); and polymer crowns (Targis) (TARG). Standardized crown preparations were
      performed on bovine roots containing NiCr metal dowels and resin cores. Crowns
      were fabricated using the ceramics listed, cemented with dual-cure resin cement,
      and submitted to compressive loads in a mechanical testing machine at a 0.5
      mm/min crosshead speed. Data were submitted to one-way ANOVA and Tukey tests, and
      fractured specimens were visually inspected under a stereomicroscope (20*) to
      determine the type of fracture. Maximum principal stress (MPS) distributions were
      calculated using finite element analysis, and fracture origin and the correlation
      with the fracture type were determined using fractography. RESULTS: Mean values
      of fracture resistance (N) for all groups were: CMC: 1383 +/- 298 (a); MMC: 1691
      +/- 236 (a); EMP: 657 +/- 153 (b); CERG: 546 +/- 149 (bc); SIGN: 443 +/- 126 (c);
      TARG: 749 +/- 113 (b). Statistical results showed significant differences among
      groups (p < 0.05) represented by different lowercase letters. Metal ceramic
      crowns presented fracture loads significantly higher than the others. Ceramic
      specimens presented high incidence of fractures involving either the core or the
      tooth, and all fractures of polymer crown specimens involved the tooth in a
      catastrophic way. Based on stress and fractographic analyses it was determined
      that fracture occurred from the occlusal to the cervical direction. CONCLUSIONS:
      Within the limitations of this study, the results indicated that the use of
      ceramic and polymer crowns without a core reinforcement should be carefully
      evaluated before clinical use due to the high incidence of failure with tooth
      involvement. This mainly occurred for the polymer crown group, although the
      fracture load was higher than normal occlusal forces. High tensile stress
      concentrations were found around and between the occlusal loading points.
      Fractographic analysis indicated fracture originating from the load point and
      propagating from the occlusal surface toward the cervical area, which is the
      opposite direction of that observed in clinical situations.

PMID- 21843230
TI  - Replacement of a lost removable partial dental prosthesis using ball-attachment
      analogs: a clinical report.
AB  - Attachment-retained removable partial dental prostheses (RPDPs) may be lost.
      Although in such situations, the RPDP should be remade, no method has yet been
      described for replacing lost attachment-retained RPDPs. This report describes a
      method for fabrication of a replacement for a lost maxillary RPDP using ball
      attachment analogs.

PMID- 21843232
TI  - Live wires: when is the analyst at work?

PMID- 21843233
TI  - Laura - or the sexual borders of need.

PMID- 21843234
TI  - Response to Jacques Andre's 'Laura - or the sexual borders of need'.

PMID- 21843235
TI  - 'Laura' falling down: comments and fantasies about Jacques Andre's essay.

PMID- 21843236
TI  - From one room to the other: a story of contamination. The relationship between
      child and adult analysis.
AB  - Does the analyst who works with both children and adults using ostensibly the
      same theoretical model perform similar mental operations in these two fields? The
      author suggests that child analysis is rooted in a different creative process
      from that of adults. Comparing the analysis of children to painting and that of
      adults to writing, and making use of the debate between Virginia Woolf and her
      sister Vanessa Bell on the relative merits of words and images, the author
      explores the psychoanalytic debate on the role of child analysis in the
      development of psychoanalytic theory and practice. Child analysis, initially
      regarded as an application of psychoanalysis, ended up acting as a catalyst for a
      true epistemological revolution in the 20th century through the work of Klein and
      Bion. Playing is not only an alternative medium to words for representing the
      unconscious but a different method for giving shape to representations through a
      specific creative process. The reverie which is born in the child analyst's
      consulting room reproduces itself through the body's actions during play, whereas
      in the adults' consulting room the analyst's capacity to dream presupposes the
      suspension of action. Child analysis, deploying a distinctive creative process
      that makes use of the body and serves itself of action in its development, may be
      said to rest on a similar creative process to that of figurative art. For this
      reason, the child analyst's mind relates to objects in a different way, being in
      a more prolonged state of fusion with these as a result of 'concentration of the
      body'. The significance of the unspeakable things that take place can often only
      be conceptualized in apres-coup. Although this difference in the development of
      the process suggests a significant distinction between the two 'arts' of child
      and adult analysis, the aesthetic sensitivity acquired through child analysis can
      be profitably used with adults, as will be demonstrated with the help of several
      clinical examples.

PMID- 21843237
TI  - Matte Blanco's thought and epistemological pluralism in psychoanalysis.
AB  - It can be seen that, although psychoanalytic pluralism is widespread, there is
      still a spirit of intolerance among the different theoretical schools. Matte
      Blanco's work allows us to think about these questions in a fresh way. Direct
      psychic experience, felt to be an indivisible whole, is characterized by the
      symmetrical mode (close to the unconscious) and projects itself in a multiple and
      decondensed manner on to the asymmetrical mode (consciousness, thought). Thus,
      psychical facts (for example, what the patient says and feels during the session)
      can be accounted for by multiple conscious representations which, however, are
      not mutually contradictory (e.g. in different theoretical approaches). Affective
      factors linked to the hope of reviving 'oceanic feelings' of fusion with a
      unified and unifying theory of the subject-analyst are also explored insofar as
      they lead to the tendency of analysts to exclude one another.

PMID- 21843238
TI  - On the construction of thinking.
AB  - In this study the author attempts to widen our understanding of language and
      thought construction by using Chinese ideograms as a model. This allows us to
      understand how concrete internal objects can coalesce to form abstract internal
      objects, e.g. concepts, ideas, symbols, and metaphors. One can establish a
      pictorial language that antedates verbal language. This is the case in the dream
      work that we routinely study. Thus, this study delves into the physiology of the
      alpha function. To this end the author not only relies on psychoanalytic concepts
      but also on concepts from philosophy and from language itself. The author
      presents the ideograms not only for discussion but also for their visual impact.
      If we really want to understand pictorial images, they must be seen and not just
      discussed from a theoretical point of view. Based on this understanding the
      author advances a proposal for the technique used in treating patients who cannot
      establish mental representations for their affect. And the technical proposal is
      illustrated in two clinical cases.

PMID- 21843239
TI  - Beyond the image.
AB  - By imposing itself as the dominant model of modern medicine, the biomedical model
      leaves little or no place for the psychical/subjective dimension of illnesses.
      The author presents a clinical case illustrating the essential contribution
      psychoanalysis can make to understanding the causes of a serious neurological
      disorder of indeterminate origin, its psychic determinism and its unconscious
      dimension. This original contribution argues in favour of the idea that
      understanding the development of neurological disorders associated with an
      unexplained lesion cannot be reduced exclusively to the organic level, and must
      not overlook the notion of unconscious. More generally, it emphasizes that body
      and mind form an integrated inseparable unit, thus breaking with the traditional
      dualistic conception of the human being.

PMID- 21843240
TI  - Reflections on the clinical implications of symbolism.
AB  - We start by stressing the idea that the process itself of constructing the symbol
      in its different components and its vicissitudes is centrally important to
      contemporary psychoanalysis as symbols are essential for thinking and for storing
      emotional experiences in our memory and for conveying our affects to others and
      to ourselves. Our implicit idea is that internal attacks are not directed only at
      the internal objects, but also include attacks on the structure or forms of the
      mental representations before and while they become constituted in symbols. It is
      by this means that destructive impulses invade the processes of symbolic
      construction. Symbols can lose their plasticity and thus silence the emotions and
      therefore cut off the patient from their meanings. Our clinical material allows
      us to increase our understanding of how the formal qualities of symbols operate
      in mental life, and how they can interfere in the capacity to work through
      emotional experiences. Finally, our reflections based on the analysis of a
      patient with difficulty in relating with the meanings of the symbols he produced
      will highlight the importance of the analyst's reverie along the process of
      formulating an interpretation. This paper is also part of a development in the
      study of the process of reverie.

PMID- 21843241
TI  - Shadows, ghosts and chimaeras: on some early modes of handling psycho-genetic
      heritage.
AB  - This paper describes three early developmental modes of handling the individual's
      psycho-genetic heritage. The first one, which characterizes normal development,
      is called living with the shadow of one's heritage. The shadow (of history, of
      life and death) is a natural counterpart of the self. The second mode, which
      accounts for more disturbed patients, is called living under the shadows of
      heritage. This type is characterized by an unconscious phantasy of the person
      being haunted by persecutory and vindictive ghosts instead of benign ancestors.
      The third mode, which might be encountered in severely disturbed patients, is
      being the shadow. This mode, called Chimerism, describes a confused organism
      which may turn against itself as parts of it are experienced as alien. On the
      unconscious level this signifies a heritage which cannot be experienced or
      mentalized as such. Rather, it is a complete chaos with moments where the hardly
      existent self is experienced as a bizarre object made up of non-combining, welded
      parts. These three modes will be examined with the help of material drawn from
      two analyses: of an autistic boy and of an adult patient who was persecuted by an
      unspeakable, horrific ancestral past.

PMID- 21843242
TI  - Reading Susan Isaacs: toward a radically revised theory of thinking.
AB  - The author views Isaacs's (1952) paper, The nature and function of phantasy, as
      making an important contribution to the development of a radically revised
      psychoanalytic theory of thinking. Perhaps Isaacs's most important contribution
      is the notion that phantasy is the process that creates meaning, and that
      phantasy is the form in which all meanings - including feelings, defense
      'mechanisms,' impulses, bodily experiences, and so on - exist in unconscious
      mental life. The author discusses both explicit formulations offered by Isaacs as
      well as his own extensions of her ideas. The latter include (1) the idea that
      phantasying generates not only unconscious psychic content, but also constitutes
      the entirety of unconscious thinking; (2) the notion that transference is a form
      of phantasying that serves as a way of thinking for the first time (in relation
      to the analyst) emotional events that occurred in the past, but were too
      disturbing to be experienced at the time they occurred and (3) a principal aim
      and function of phantasy is that of fulfilling the human need to get to know and
      understand the truth of one's experience. The author concludes by discussing the
      relationship between Isaacs's concept of phantasy and Bion's concepts of alpha
      function and the human need for the truth, as well as the differences between
      Fairbairn's and Isaacs's conceptions of the nature of unconscious internal object
      relationships.

PMID- 21843243
TI  - Dynamics of psychoanalytic supervision: a heuristic model.
AB  - This paper presents a heuristic model for the dynamics of psychoanalytic
      supervision. It is not a manual for how to perform supervision, but a model for
      how to identify and think about the complex elements and forces influencing the
      supervisory process. The point of departure is that psychoanalysis is a composite
      craft in which seemingly contrary elements like strict rules and creative
      intuitions have their place and interact. Several aspects of supervision are
      discussed: aims, learning processes, teaching methods, relationship, emotional
      atmosphere and evaluation. Competence is given a pivotal place in the model. The
      main feature of the model is that these aspects of supervision are all seen as
      suspended in a field of dynamic tensions between phenomena in real or apparent
      opposition. One example of this is the tension in the supervisory relationship
      between supervisor as instructor acting as an authority for the candidate whilst
      being a mentor fostering autonomy in the candidate. It is argued that related
      kinds of dynamics characterize several aspects of psychoanalytic supervision and
      that these tensions are inherent in analytic work. In conclusion a key word
      picture of the model is presented.

PMID- 21843244
TI  - Love, drive and desire in the works of Freud, Lacan and Proust.
AB  - Both Freud and Lacan have made love the object of scientific enquiry, which is in
      itself remarkable, since we usually turn this subject over to literary and
      philosophical treatment. This article discusses Freud and Lacan's contributions
      to the psychology of love through dialogue with Marcel Proust's seminal novel,
      Remembrance of Things Past, with special emphasis on the middle sections. The
      point of departure is love's manifestation in the analytical situation. Freud has
      described transference love as both resistance and as an extreme variant of
      normal falling in love, to which Lacan adds the deceptive character of
      transference. From transference love the investigation continues to the
      contradictions Freud has described in Three Essays on the Theory of Sexuality as
      love's affectionate and sensual currents. Lacan contributes the concept of
      desire, which must be distinguished from drive and love. The differentiation
      between desire, drive and love introduces the perspective necessary for a
      psychoanalytic reading of Proust's opus. The main objective is a reading of the
      protagonists, Albertine and the Baron de Charlus, as representatives of the
      vicissitudes of love and drive, respectively.

PMID- 21843245
TI  - The OEdipus complex, crystallizer of the debate between psychoanalysis and
      anthropology.
AB  - The way that anthropologists understand the Oedipus complex, in particular, is a
      good example of how they understand psychoanalysis in general. Indeed, it has
      crystallized a set of reactions marked by ignorance, misunderstanding, distortion
      and screening out and at the same time has provoked suspicion among
      anthropologists as to psychoanalysis, according to the preconceptions of the
      various schools of thought and authors implied, and this from the very first
      contacts up to nowadays. In what way did the psychoanalysts contribute to this
      and what representation did they, in turn, elaborate of anthropology? The purpose
      of this paper is to expose the epistemological and historical conditions of the
      emergence of this debate, and then to develop it by following chronology up to
      the 1950s and 1960s, while differentiating three major cultural areas, Great
      Britain, the USA and France, in order to get a clearer picture. From that point
      on, we will try to diversify our inquiry and to formulate some interpretative
      hypotheses. In particular, we think that a traumatic event may have inaugurated
      and organized the history of the relationship between the two disciplines,
      producing a situation of acculturation with multiple impacts, if we identify them
      with two cultures coming into contact: what is at stake here is Totem and Taboo
      in which Freud carries through the first major psychoanalytical approach of the
      interpretation of ethnographic facts, that leads him to transplant the
      universality of the Oedipus complex to the very root of the first social
      institutions and to pinpoint the presence of unconscious processes in their
      genesis.

PMID- 21843246
TI  - Catharsis: Psychoanalysis and the theatre.
AB  - The notion of catharsis, in relation to tragedy, was introduced by Aristotle in
      his work Poetics. Over the centuries, Aristotle's innovative and enigmatic
      reference to this process has been widely commented on and given rise to intense
      controversy. In 1895, Freud and Breuer reconsidered this notion in their Studies
      on Hysteria, where they present the so-called cathartic therapeutic method. It is
      not, however, this aspect of psychoanalytical theory that the author of this
      article seeks to elucidate: drawing on a detailed study of the references to
      tragic catharsis in the work of Freud and Lacan, the author proposes to examine
      their implications for psychoanalytic treatment.With specific reference to
      Freud's article Psychopathic characters on the stage (1905) and Lacan's
      commentary on Sophocles' Antigone (1960), the author argues that catharsis is to
      be understood not so much as a mechanism of discharge linked to abreaction, but
      rather as the actual analytic process itself during which the Subject is
      'unveiled' and thus faced with the enigma of his own desire.

PMID- 21843247
TI  - Lewis Carroll and psychoanalysis: why nothing adds up in wonderland.
AB  - Each generation of psychoanalyst has found different things to value and
      sometimes to censure in Lewis Carroll's remarkable fiction and flights of fancy.
      But what does Carroll's almost 'surrealist' perspective in the Alice stories tell
      us about the rituals and symbols that govern life beyond Wonderland and Looking
      Glass World? Arguing that Carroll's strong interest in meaning and nonsense in
      these and later works helps make the world strange to readers, the better to show
      it off-kilter, this essay focuses on Jacques Lacan's Carroll - the writer
      logician who stressed, as Lacan did, the difficulty and price of adapting to the
      symbolic order. By reconsidering Lacan's 1966 homage to the eccentric Victorian,
      I argue that Carroll's insight into meaning and interpretation remains of key
      interest to psychoanalysts intent on hearing all that he had to say about psychic
      life.

PMID- 21843248
TI  - On: Letter from Jerusalem.

PMID- 21843249
TI  - On: Unacknowledged and acknowledged trauma.

PMID- 21843251
TI  - Dr Paul Weston and the bloodstained couch.

PMID- 21843252
TI  - N-Nicotinoyl dopamine, a novel niacinamide derivative, retains high antioxidant
      activity and inhibits skin pigmentation.
AB  - We synthesized a novel derivative of a well-known skin-lightening compound
      niacinamide, N-nicotinoyl dopamine (NND). NND did not show inhibitory effects of
      tyrosinase and melanin synthesis in B16F10 mouse melanoma cells. However, NND
      retains high antioxidant activity without affecting viability of cells. In a
      reconstructed skin model, topical applications of 0.05% and 0.1% NND induced skin
      lightening and decreased melanin production without affecting the viability and
      morphology of melanocytes and overall tissue histology. Moreover, no evidence for
      skin irritation or sensitization was observed when 0.1% NND emulsion was applied
      onto the skin of 52 volunteers. The effect of NND on skin lightening was further
      revealed by pigmented spot analyses of human clinical trial. Overall, NND
      treatment may be a useful trial for skin lightening and treating pigmentary
      disorders.

PMID- 21843253
TI  - Double lumen aortic arch or persistence of fifth aortic arch?- Report of a case
      with no associated cardiac defects and literature review.
AB  - Different vascular abnormalities have been reported under the denomination of
      "persistence of the fifth aortic arch." Detailed studies on experimental
      embryology raised the discussion about the existence of the fifth aortic arch as
      an embryological structure, both in humans and mammals. In 1969 the Van Praaghs
      described the occurrence of double left aortic arch, denominating such anomaly as
      persistence of the fifth arch. We describe here a female patient showing the
      presence of an anomalous vessel in parallel with the aortic arch. The finding was
      occasional, during a preoperative evaluation for cholecystectomy.

PMID- 21843254
TI  - Left ventricular torsion and strain in patients with repaired tetralogy of Fallot
      assessed by speckle tracking imaging.
AB  - BACKGROUND: In patients with tetralogy of Fallot (TOF), left ventricular (LV)
      dysfunction is an important factor associated with poor clinical outcome.
      OBJECTIVE: The purpose of this study was to investigate the torsion and
      multidirectional strain of the LV in patients with TOF. METHODS:
      Echocardiographic images were prospectively acquired in 29 patients who underwent
      TOF repair (age range, 5-25 years) and in 29 normal controls. Torsion and
      circumferential and longitudinal strain of the LV were assessed using speckle
      tracking imaging. RESULTS: The torsion in patients was smaller compared to that
      in the controls due to small apical rotation and/or inverse basal rotation (P <
      0.01). Torsion and untwisting rates decreased with increasing age (R = 0.37, P <
      0.05). Basal circumferential strain and strain rate (SR) at systole and diastole
      decreased with age (R = 0.58; R = 0.57; R = 0.57, all P < 0.001) and were smaller
      in patients compared to those in the controls (all P < 0.01). Septal longitudinal
      strain and SR at systole and diastole decreased with age (R = 0.52; R = 0.62; R =
      0.71, all P < 0.001) and were smaller than those of the controls (P < 0.01),
      although lateral longitudinal strain and SR were relatively maintained.
      CONCLUSION: Abnormal torsion and strain pattern of the LV were observed in
      patients without symptoms of cardiac failure. Assessment of torsion and strain is
      a very sensitive tool to detect the early deterioration of LV function in
      patients with TOF.

PMID- 21843256
TI  - Ventricular torsion and untwisting: further insights into mechanics and timing
      interdependence: a viewpoint.
AB  - Ventricular torsion and untwisting are essential for normal ventricular function
      and their mechanisms are related to the temporal responses of the helical and
      circular muscle fibers that comprise cardiac architecture. Explanation of the
      presystolic isovolumic contraction (IVC) period is essential for analysis of
      these interactions. Structural and imaging studies by magnetic resonance, speckle
      tracking, velocity vector encoding, and sonomicrometer crystals are described to
      define why and how different muscular components contract asynchronously.
      Mechanical and functional relationships are described for pre-systolic IVC,
      torsion, postejection isovolumic interval, and rapid and slow filling. Circular
      fibers dominate to cause pre- and posttwisting global counterclockwise and
      clockwise movement, and helical fibers govern torsion whereby the base rotates
      clockwise and apex counterclockwise; untwisting cannot begin until torsion is
      completed. Prolonged torsion extends into the postejection isovolumic interval
      and delays untwisting, and is caused by prolonged contraction of the right-handed
      helical arm or descending segment of the helical ventricular myocardial band that
      narrows the ~80 ms "timing hiatus" between end of shortening of the descending
      and the ascending segment or left-handed arm of the helical muscle. Longer
      torsion duration by this mechanism becomes the common theme for unbalanced
      torsion and untwisting in diastolic dysfunction, physiological, structural, and
      electrical disease processes, whose management may be guided by changing the
      interconnected reasons for these adverse mechanical and timing factors.

PMID- 21843257
TI  - Operative drains after pancreatic resection--the Titanic is sinking.

PMID- 21843258
TI  - Islet cell autotransplantation and chronic pancreatitis--still options.

PMID- 21843259
TI  - Antitumour activity of sunitinib in combination with gemcitabine in experimental
      pancreatic cancer.
AB  - BACKGROUND: Gemcitabine (Gem) has limited clinical benefits in pancreatic ductal
      adenocarcinoma (PDAC). Sunitinib (Su) is a novel, multi-target receptor tyrosine
      kinase inhibitor that has antitumour activities. This study tested the benefits
      of combined gemcitabine and sunitinib in PDAC. METHODS: Cell viability and
      protein expression were evaluated by WST-1 assay and Western blotting. Tumour
      growth and survival experiments were performed in murine xenografts. RESULTS: In
      PDAC cells, Gem, Su and Su + Gem, respectively, caused 28%, 22% and 48%
      inhibition in proliferation at 100 nM. In endothelial cells, Gem, Su and Su +
      Gem, respectively, caused 49%, 32% and 72% inhibition in proliferation. In
      fibroblasts, Gem, Su and Su + Gem, respectively, caused 65%, 14% and 79%
      inhibition in proliferation. Su increased apoptosis, as evidenced by the cleavage
      of caspase-3 and PARP-1 proteins. Net tumour growth compared with controls in the
      Gem, Su and Su + Gem groups was 57%, 6% and 1%, respectively. Intratumoral
      proliferative activity was reduced by 33%, 82% and 75% in the Gem, Su and Su +
      Gem groups, respectively, compared with controls. Median survival in the control,
      Su, Gem and Su + Gem groups was 16, 21, 24 and 30 days, respectively (P=0.007).
      CONCLUSIONS: These findings support a combination approach using multi-target
      antiangiogenic agents such as sunitinib with standard gemcitabine therapy in the
      treatment of PDAC.

PMID- 21843260
TI  - The prognostic importance of lymphovascular invasion in cholangiocarcinoma above
      the cystic duct: a new selection criterion for adjuvant therapy?
AB  - OBJECTIVE: Criteria for selecting patients to receive adjuvant chemotherapy in
      cases of resected intrahepatic or hilar cholangiocarcinoma (CC) are lacking. Some
      clinicians advocate the provision of adjuvant therapy in patients with lymph node
      (LN)-positive disease; however, nodal assessment is often inadequate. The aim of
      this study was to identify a surrogate criterion based on primary tumour
      characteristics. METHODS: All patients who underwent resection for hilar or
      intrahepatic CC at a single institution between January 2000 and September 2009
      were identified from a prospectively maintained database. Pathological factors
      were recorded. The primary outcome assessed was overall survival (OS). RESULTS:
      In total, 69 patients underwent resection for hilar (n=34) or intrahepatic (n=35)
      CC. Their median age was 66 years and 27 patients (39%) were male. Median follow
      up was 22 months and median OS was 17 months. Median tumour size was 5 cm.
      Overall, 23% of patients had a positive resection margin, 44% had perineural
      invasion, 32% had lymphovascular invasion (LVI) and 25% had positive LNs. The
      median number of LNs removed was two and the median number of positive LNs was
      zero. The presence of LVI was associated with reduced OS (11.9 months vs. 23.1
      months; P=0.023). After accounting for all other adverse tumour factors, the
      presence of LVI persisted as the only negative prognostic factor for OS on
      multivariate Cox regression. CONCLUSIONS: In patients who had undergone resection
      of hilar or intrahepatic CC, the presence of LVI was strongly associated with
      reduced OS. Thus the finding of LVI may potentially be used as a criterion in the
      selection of patients for adjuvant chemotherapy.

PMID- 21843261
TI  - Lymphadenectomy in the staging and treatment of intrahepatic cholangiocarcinoma:
      a population-based study using the National Cancer Institute SEER database.
AB  - OBJECTIVES: Although lymphatic spread is common in intrahepatic
      cholangiocarcinoma (ICC), lymphadenectomy is not widely performed as part of
      operative resection in this disease. The objectives of this study were to assess
      national trends for lymphadenectomy and its impact on survival in patients with
      ICC. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End
      Results (SEER) registry was queried to identify patients with ICC (n=4893)
      reported during 1988-2007. Kaplan-Maier and Cox proportional hazards regression
      were used to analyse survival. RESULTS: Five-year overall survival (OS) was 5.2%.
      Lymph node (LN) status was available for 48.9% (n=2391) of patients. Histologic
      LN evaluation was performed in 13.5% (n=658) of patients for a median of two
      (interquartile range: 1-3) LNs. During the study period, the frequency of
      histologic LN assessment (P=0.78) did not change in liver resection patients. In
      the 733 resected patients, positive vs. negative LN status was associated with
      worse 5-year OS of 8.4% vs. 25.9%, respectively (hazard ratio=1.8; P<0.001).
      CONCLUSIONS: Nodal status is an important prognostic factor for survival in
      patients diagnosed with ICC. In the USA, few patients undergo hepatic resection
      with lymphadenectomy; therefore, the clinical benefit of formal lymphadenectomy
      in ICC remains unknown.

PMID- 21843262
TI  - Laparoscopic spleen-preserving distal pancreatectomy in elderly subjects: splenic
      vessel sacrifice may be associated with a higher rate of splenic infarction.
AB  - BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy has gained
      popularity in recent years. Splenic preservation can be achieved with or without
      splenic vessel preservation (SVP). The potential morbidity of this approach in
      patients aged >70 years has not been well defined. METHODS: Ten patients aged >70
      years underwent attempted laparoscopic spleen-preserving distal pancreatectomy
      within a 2-year period. Multiple patient parameters were examined and chi-squared
      analysis was used to evaluate the association between the operative technique
      (SVP or splenic vessel division [SVD]) and splenic infarction. The Mann-Whitney
      test was used to compare the SVP and SVD groups with regard to age, estimated
      blood loss (EBL), operating time, splenic volume and length of stay (LoS).
      RESULTS: Median age was 81 years (range: 71-92 years). Operating room time, LoS,
      EBL and complication rates were similar to those reported in published series of
      younger patients. In four patients, the splenic vessels were divided in a manner
      relying on short gastric collateral flow; SVP was achieved in all other patients.
      All four patients who underwent SVD developed splenic infarcts and three required
      splenectomy to manage this (P=0.002). Median LoS was increased in the SVD group
      (9.3 days vs. 4.3 days; P=0.053). Estimated blood loss was higher in the SVP
      group (200 ml vs. 100 ml; P=0.091). One pancreatic leak occurred. There were no
      mortalities. CONCLUSIONS: Spleen-preserving laparoscopic distal pancreatectomy
      can be performed safely in elderly patients, with results comparable with those
      achieved in younger subjects. However, elderly patients undergoing division of
      the splenic artery and vein may be at higher risk for splenic infarct and the
      aetiology of this is unclear.

PMID- 21843263
TI  - Recurrent hepatocellular carcinoma after liver transplant: identifying the high
      risk patient.
AB  - BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver
      transplantation (LT) is rarely curable. However, in view of the advent of new
      treatments, it is critical that patients at high risk for recurrence are
      identified. METHODS: Patients undergoing LT for HCC at a single centre between
      2002 and 2010 were reviewed and data on clinical parameters and explant pathology
      were analysed to determine factors associated with HCC recurrence. All necrotic
      and viable tumour nodules were included in explant staging. All patients
      underwent LT according to the United Network for Organ Sharing (UNOS) Model for
      End-stage Liver Disease (MELD) tumour exception policies. RESULTS: Liver
      transplantation was performed in 122 patients with HCC during this period. Rates
      of recurrence-free survival in the entire cohort at 1 year and 3 years were 95%
      and 89%, respectively. Thirteen patients developed HCC recurrence at a median of
      14 months post-LT. In univariate analysis the factors associated with HCC
      recurrence were bilobar tumours, vascular invasion, and stage exceeding either
      Milan or University of California San Francisco (UCSF) Criteria. Multivariate
      analysis showed pathology outside UCSF Criteria was the major predictor of
      recurrence; when pathology outside UCSF Criteria was found in combination with
      vascular invasion, the predicted 3-year recurrence-free survival was only 26%.
      CONCLUSIONS: Explant pathology can be used to predict the risk for recurrent HCC
      after LT, which may allow for improved adjuvant and management strategies.

PMID- 21843264
TI  - Radiologic and intraoperative detection of need for mesenteric vein resection in
      patients with adenocarcinoma of the head of the pancreas.
AB  - OBJECTIVE: The need for mesenteric venous resection (MVR) is determined by a
      combination of preoperative radiologic and intraoperative surgical assessments. A
      single-centre review was performed to determine how efficient these processes are
      in evaluating the need for MVR. METHODS: A retrospective study was performed of
      343 patients who received resection for adenocarcinoma of the head of the
      pancreas, 100 of whom underwent MVR. Three radiologic signs (abutment, fat plane
      obliteration, focal narrowing) were evaluated for their ability to predict the
      need for MVR. Pathologic assessment was performed to determine if MVR had been
      necessary to achieve negative-margin (R0) resection. Microscopic tumour in the
      vein wall, or within 1 mm of the vein wall, was considered to indicate that MVR
      had been necessary to achieve an R0 resection. RESULTS: Radiologic evaluation
      (showing any of the three signs) had sensitivity of only 60%. Overall, 40% of the
      patients who required MVR showed none of the signs. Specificity was 77%. A total
      of 80% of patients who underwent MVR had either microscopic invasion or abutment.
      R0 resection at the vein margin was achieved in 98% of patients in both the MVR
      and non-MVR groups. CONCLUSIONS: Preoperative radiologic evaluation is not highly
      reliable in predicting the need for MVR. Therefore, surgical teams performing
      resections of cancers of the head of the pancreas must be skilled in MVR as the
      need for this procedure may arise unexpectedly. Surgical assessment of the need
      for MVR has an accuracy of about 80% and is nearly 100% accurate in determining
      when MVR is not required.

PMID- 21843265
TI  - Engineered T cells for pancreatic cancer treatment.
AB  - OBJECTIVE: Conventional chemotherapy and radiotherapy produce marginal survival
      benefits in pancreatic cancer, underscoring the need for novel therapies. The aim
      of this study is to develop an adoptive T cell transfer approach to target
      tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen
      that is frequently expressed by pancreatic cancer cells. METHODS: Expression of
      PSCA on cell lines and primary tumour samples was confirmed by
      immunohistochemistry. Healthy donor- and patient-derived T cells were isolated,
      activated in vitro using CD3/CD28, and transduced with a retroviral vector
      encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these
      cells to kill tumour cells was analysed by chromium-51 (Cr(51)) release. RESULTS:
      Prostate stem cell antigen was expressed on >70% of the primary tumour samples
      screened. Activated, CAR-modified T cells could be readily generated in
      clinically relevant numbers and were specifically able to kill PSCA-expressing
      pancreatic cancer cell lines with no non-specific killing of PSCA-negative target
      cells, thus indicating the potential efficacy and safety of this approach.
      CONCLUSIONS: Prostate stem cell antigen is frequently expressed on pancreatic
      cancer cells and can be targeted for immune-mediated destruction using CAR
      modified, adoptively transferred T cells. The safety and efficacy of this
      approach indicate that it deserves further study and may represent a promising
      novel treatment for patients with pancreatic cancer.

PMID- 21843266
TI  - Duct-to-duct biliary reconstruction in patients with primary sclerosing
      cholangitis undergoing liver transplantation.
AB  - BACKGROUND: Reconstruction of biliary drainage after liver transplantation (LTx)
      in patients with primary sclerosing cholangitis (PSC) has been a matter of
      controversy. Over recent years, the traditional method of Roux-en-Y
      hepaticojejunostomy (RY) has been challenged by duct-to-duct (DD) biliary
      reconstruction. METHODS: This study represents a retrospective review of biliary
      complications, patient and graft survival after LTx in PSC patients based on type
      of biliary reconstruction. Outcomes of DD reconstruction in this group of
      patients and non-PSC patients are compared. RESULTS: A total of 53 primary LTx
      procedures were performed for PSC between August 2005 and July 2010. Seven
      patients were excluded because unexpected cholangiocarcinoma was found in the
      explants (n=3) or because they received partial livers (n=4). Biliary
      reconstruction was performed as DD in 18 patients and RY in 28 patients. There
      were no bile leaks. Anastomotic stricture occurred in two (11%) patients in the
      DD group and one (4%) in the RY group. Two (7%) patients in the RY group
      developed non-PSC intrahepatic strictures and one had recurrence of PSC. Rates of
      1- and 3-year patient and graft survival in the RY and DD groups were 96.7% and
      96.7%, and 100% and 94.5%, respectively. In a group of 34 randomly selected
      patients transplanted for a non-PSC diagnosis with DD reconstruction during the
      same period, the anastomotic stricture rate was 9% and 1- and 3-year patient and
      graft survival rates were 97.0% and 88.5%; differences were not significant.
      CONCLUSIONS: Duct-to-duct biliary reconstruction at the time of LTx in selected
      PSC patients is both effective and safe, and shows outcomes comparable with those
      of RY reconstruction in these patients and those of DD reconstruction in non-PSC
      patients.

PMID- 21843267
TI  - Laparoscopic treatment of liver tumours using a two-needle probe bipolar
      radiofrequency ablation device.
AB  - BACKGROUND: Many hepatobiliary centres are increasingly utilizing
      thermocoagulative devices such as bipolar-radiofrequency ablation (B-RFA).
      Compared with monopolar-radiofrequency ablation (M-RFA), B-RFA does not require
      grounding pads, thereby avoiding dermal burn injuries, and does not position
      probes directly into the tumour but rather on the perimeter. Additionally, B-RFA
      can precoagulate parenchyma to assist in hepatic resection. Herein, we report our
      early experience using B-RFA. METHODS: A retrospective review identified 68
      patients who underwent M-RFA or B-RFA between June 2004 and September 2010 in an
      academic centre. Peri-operative metrics were analysed. RESULTS: M-RFA was used to
      treat 30 patients, whereas B-RFA was used for 17 patients. There were no
      differences in peri-operative metrics, survival or disease recurrence between M
      RFA and B-RFA. Seventeen additional patients underwent B-RFA precoagulation
      during laparoscopic resection (segmentectomy in eleven patients and multi
      segmental resection in six patients). Four patients with multifocal disease
      underwent procedures that combined B-RFA with resection. CONCLUSIONS: The early
      experience utilizing B-RFA demonstrates equivalency to M-RFA with respect to peri
      operative metrics and survival. Moreover, B-RFA can be utilized to precoagulate
      tissue during a planned resection, making it not only a useful tool for tumour
      therapy but also a useful adjunct during surgical resections.

PMID- 21843268
TI  - Is intra-operative ultrasound still useful for the detection of a hepatic tumour
      in the era of modern pre-operative imaging?
AB  - BACKGROUND: The current role of intra-operative ultrasound (IOUS) is questioned
      because of recent progress in medical imaging. The aim of the present study was
      to determine the accuracy of IOUS in the detection of a hepatic tumour (HT)
      compared with a pre-operative multi-detector computed tomography (MDCT) scan and
      magnetic resonance imaging (MRI). METHODS: This retrospective study included 418
      patients evaluated using an 8-slice MDCT scan (SCAN8), 64-slice MDCT scan
      (SCAN64) and MRI alone or combined with a computed tomography (CT) scan. The
      pathological result was used as a gold standard. RESULTS: Correlation rates for
      the number of detected lesions compared with pathology results were 0.627 for
      SCAN8, 0.785 for SCAN64, 0.657 for MRI and 0.913 for IOUS. Compared with
      pathology, the rate of concordance was significantly higher with IOUS (0.871)
      than with SCAN8 (0.736; P=0.011), SCAN64 (0.792; P<0.001) and MRI (0.742;
      P<0.001). IOUS was responsible for a change in operative strategy in 16.5% of
      patients. Surgery was extended in 12.4%, limited in 1.7% and abandoned in 2.4%.
      CONCLUSIONS: Compared with cross-sectional pre-operative imaging, IOUS is still
      superior for the detection of HT and the planning of surgery. IOUS remains
      recommended as a routine procedure in patients having a hepatic resection in the
      era of modern pre-operative imaging.

PMID- 21843269
TI  - Novel three-dimensional imaging technique improves the accuracy of hepatic
      volumetric assessment.
AB  - BACKGROUND: With pre-operative prediction of liver volume becoming increasingly
      important to safely carry out complex hepatic resections, the aim of the present
      study was to validate the accuracy of a three-dimensional (3-D) liver surgery
      operative planning software in performing hepatic volumetry. METHODS: Between
      1999 and 2007, we performed 29 live donor liver resections for transplantation.
      Eleven patients had pre-operative volumetry performed by radiologists from either
      computed tomography (CT) or magnetic resonance (MR) imaging with documentation of
      the corresponding specimen weight. Retrospectively, images were uploaded into
      ScoutTM where 3-D models of each case were generated to perform volumetry. A
      correlational analysis was performed followed by an accuracy comparison. RESULTS:
      Estimations by both radiologists and ScoutTM were significantly correlated with
      the specimen weights, P <= 0.0001. Compared with radiologists' volumetry, ScoutTM
      significantly improved overall accuracy [per cent error (PE) 20.0% +/- 5.3 vs.
      32.9% +/- 5.7, P=0.005], accuracy of CT-based estimations (PE 23.2% +/- 6.7 vs.
      37.2% +/- 6.9, P=0.023) and accuracy of the left lateral section (PE 11.1% +/-
      3.9 vs. 26.6% +/- 6.8, P=0.027). DISCUSSION: This 3-D planning software is a
      valid tool for use in volumetry. Significance is greatest for CT-based models of
      the left lateral section. This approach gives surgeons the ability to assess
      volumetrics and actively plan resections.

PMID- 21843271
TI  - RNase Y is responsible for uncoupling the expression of translation factor IF3
      from that of the ribosomal proteins L35 and L20 in Bacillus subtilis.
AB  - RNase Y is a novel endoribonuclease affecting global mRNA metabolism. We show
      that this nuclease affects the expression of the Bacillus subtilis infC-rpmI-rplT
      operon, encoding translation initiation factor IF3 and the ribosomal proteins L35
      and L20. This operon is autoregulated by a complex L20-dependent transcription
      attenuation mechanism. L20 binds to a phylogenetically conserved domain on the 5'
      untranslated region of the infC mRNA which mimics the L20 binding sites on 23S
      rRNA. We have identified a second promoter (P1) upstream of the previously
      identified promoter (P2). The P1, but not the P2, readthrough transcript is
      stabilized in a strain depleted for RNase Y. However, under these conditions infC
      biosynthesis is repressed threefold. We show that the unprocessed P1 transcript
      is non-functional for IF3 translation but fully competent to express the co
      transcribed ribosomal protein genes. RNase Y cleavage of the P1 transcript
      creates an entry site for the 5'-3' exonucleolytic activity of RNase J1 which
      degrades the infC mRNA when translation initiation efficiency is low. A second
      RNase Y cleavage is crucial for initiating degradation of the prematurely
      terminated infC leader RNAs, including the L20 operator complex, which permits
      efficient recycling of the L20 protein.

PMID- 21843273
TI  - Meta-analysis of neuropsychological functioning in euthymic bipolar disorder: an
      update and investigation of moderator variables.
AB  - OBJECTIVES: Cognitive impairment is frequently observed among individuals with
      bipolar disorder during acute and euthymic phases of the illness. The purpose of
      this study was to provide an updated meta-analysis on the neuropsychological
      functioning of euthymic bipolar disorder individuals and to explore study design,
      demographic, and clinical variables that could moderate observed effects.
      METHODS: Searches were conducted on Medline and PsychInfo databases and 28
      studies were selected that met inclusion criteria. A total of 28 cognitive
      variables were examined in the meta-analysis. The effects of four continuous
      (age, percent female, education, and illness duration) and two dichotomous
      (clinical course and diagnostic rigor) moderator variables were explored.
      RESULTS: Compared to controls, euthymic bipolar disorder individuals demonstrated
      impaired neuropsychological functioning across almost all domains, with medium
      large effect sizes. Notably, vocabulary and word reading did not differ from
      controls. Sex did not impact neuropsychological functioning, and
      neuropsychological impairment decreased as education increased. Contrary to
      expectations, age and illness duration were negatively correlated with cognitive
      impairment. Diagnostic rigor of euthymia did not appear to impact effect sizes;
      however, clinical course received some tentative support as a moderator variable.
      CONCLUSIONS: Current results suggest that generalized, rather than specific,
      cognitive impairment characterizes euthymic bipolar disorder. Age, illness
      duration, education, and clinical course may moderate these broad cognitive
      effects. Against this general impairment backdrop, there may be a relative
      preservation of crystallized verbal ability.

PMID- 21843272
TI  - The impact of neurocognitive impairment on occupational recovery of clinically
      stable patients with bipolar disorder: a prospective study.
AB  - OBJECTIVE: Many patients with bipolar disorder do not regain their premorbid
      level of occupational functioning even after mood episodes have resolved. The
      reasons for this are not well understood. We evaluated the relationship between
      neurocognition and occupational function in bipolar disorder patients, following
      symptomatic recovery. METHODS: A total of 79 previously employed adults with
      bipolar I disorder who achieved symptomatic recovery (i.e., at least six weeks
      clinically euthymic) following a manic episode underwent a neurocognitive
      evaluation and assessment of occupational functioning. Study participants were
      evaluated every three months thereafter for up to nine months. Factor analysis
      was applied to reduce the initial set of neurocognitive variables to five
      domains: episodic memory, working memory/attention, executive function, visual
      scanning, and speed of processing. Multiple logistic regression models were used
      to examine the joint predictive values of these domains for determining
      occupational recovery. RESULTS: At the time of symptomatic recovery, four of five
      neurocognitive factors were significant predictors of concomitant occupational
      recovery and the fifth, executive function, showed a trend in the same direction.
      For those not occupationally recovered at baseline, longitudinal analyses
      revealed that changes between baseline and the three-month follow-up timepoint in
      most cognitive domains were robust and highly significant predictors of
      occupational recovery at three months. CONCLUSIONS: These findings indicate that
      better neurocognitive function in multiple domains and improvement in these
      domains over time are strongly predictive of subsequent occupational recovery.
      Treatments that target cognitive deficit may therefore have potential for
      improving long-term vocational functioning in bipolar illness.

PMID- 21843274
TI  - Insight in bipolar disorder: associations with cognitive and emotional processing
      and illness characteristics.
AB  - OBJECTIVE: To investigate the multifactorial relationship between illness
      insight, cognitive and emotional processes, and illness characteristics in
      bipolar disorder patients. METHODS: Data from 85 euthymic or mildly to moderately
      depressed bipolar disorder patients were evaluated. Insight was measured using
      the Mood Disorder Insight Scale (total score and subscale scores: awareness of
      illness, symptom attribution, and need for treatment). Cognitive and emotional
      functioning was measured in four domains (processing speed, memory, executive
      functioning, and emotional learning) in addition to premorbid IQ. Illness
      characteristics were assessed using the Mini-International Neuropsychiatric
      Interview, the Questionnaire for Bipolar Disorder, and the Inventory of
      Depressive Symptomatology-self rating scale. Regression analyses were performed
      for the whole sample. Post-hoc, interactions with lifetime psychotic features
      (LPF) were statistically tested and if significant, analyses were repeated for
      patients with (n = 36) and without (n = 49) LPF separately. RESULTS: In the whole
      group, better insight was associated with lower processing speed, better memory
      performance, increased emotional learning, higher level of depressive symptoms,
      and longer duration of illness. Patients with LPF had worse awareness of illness,
      but better symptom attribution than patients without LPF. No group differences
      for need for treatment and overall insight were found. Finally, processing speed
      significantly predicted subscores for symptom attribution in patients with LPF
      only. CONCLUSIONS: Cognitive functioning as well as impairments in emotional
      learning and psychotic features independently contributes to impaired insight in
      bipolar disorder. Processing speed seems to be a key variable in the prediction
      of insight in patients with LPF and not in patients without LPF.

PMID- 21843275
TI  - Cognitive styles in hypomanic episodes of bipolar I disorder.
AB  - OBJECTIVES: Cognitive vulnerability-stress theories have recently been extended
      to bipolar disorder by suggesting that an activation of negative cognition might
      lead to depressive mood episodes and an activation of positive cognition might
      lead to manic mood episodes. Alternatively, the manic defense hypothesis claims
      that hypomanic and manic states are not the opposite of depression but rather
      contain similar underlying negative cognitions. The objective of this study was
      to further evaluate these theories by examining the cognitive patterns in bipolar
      I hypomania. METHODS: We compared 15 hypomanic bipolar I disorder patients, 26
      remitted bipolar I disorder patients, and 21 healthy individuals in a cross
      sectional study. All participants completed the Dysfunctional Attitude Scale, the
      Attributional Style Questionnaire, the Emotional Stroop Task, and the Emotional
      Auditory Verbal Learning Test. RESULTS: Hypomanic bipolar disorder individuals
      showed cognitions associated with depressive states as well as cognitions
      associated with manic states. The results for the remitted bipolar disorder
      patients paralleled those for the control group. CONCLUSION: Dysfunctional
      cognition in bipolar disorder seems to relate to state rather than to trait.
      Hypomania includes depression-related as well as mania-related cognitions and can
      therefore not be considered as the mere opposite of depression.

PMID- 21843276
TI  - Visuospatial working memory deficits in remitted patients with bipolar disorder:
      susceptibility to the effects of GABAergic agonists.
AB  - OBJECTIVES: Visuospatial working memory (VSWM) deficit under high working memory
      (WM) load deserves further investigation as a potential trait marker for bipolar
      disorder (BPD). However, VSWM performances may depend on basic neurocognitive
      processes and are possibly compromised by neurocognitive effects of psychotropic
      medications. METHODS: A total of 32 remitted BPD patients and 39 healthy controls
      undertook parametric VSWM tasks and assessments for selective attention,
      sustained attention, psychomotor speed, mental flexibility, and Wechsler Adult
      Intelligence Scale-III full IQ. Using a multivariate model and trend analysis and
      controlling for other basic neurocognitive ability, the effects of mood
      stabilizers, antipsychotics, GABAergic agonists, and anticholinergics on VSWM
      performances were explored by post-hoc analysis comparing performances across WM
      loads between healthy controls and patients treated and not treated with a
      specific medication. RESULTS: Remitted BPD patients showed more pronounced
      performance declines in VSWM performances as WM loads increased, indicating
      inefficient VSWM processing. The VSWM deficits of remitted patients were
      independent of their impairments in attentional processes or psychomotor speed.
      Among the medications, only GABAergic agonists were associated with impaired VSWM
      performances. CONCLUSIONS: Remitted BPD patients had WM-load-dependent VSWM
      processing deficits after controlling for neurocognitive performances. As these
      deficits were associated with the use of GABAergic agonists, altered GABAergic
      neurotransmission might be involved with the underlying mechanisms of the
      impaired VSWM processing of BPD. Since GABAergic agonist use is often continued
      from the acute to the remitted phase in BPD and might potentially affect the
      functional recovery, clinicians should be aware of these neurocognitive side
      effects, even at low dosages. Close monitoring and timely discontinuation of
      GABAergic agonists is of utmost importance for clinical practice.

PMID- 21843277
TI  - Suicidal attempts in bipolar disorder: results from an observational study
      (EMBLEM).
AB  - OBJECTIVES: To compare patients with and without a history of suicidal attempts
      in a large cohort of patients with bipolar disorder and to identify variables
      that are associated with suicidal behavior. METHODS: European Mania in Bipolar
      Longitudinal Evaluation of Medication (EMBLEM) is a two-year, prospective,
      observational study that enrolled 3,684 adult patients with bipolar disorder and
      initiated or changed oral treatment for an acute manic/mixed episode. Of those,
      2,416 patients were eligible for the two-year follow-up. Only baseline
      characteristics were studied in the present study, included sociodemographic
      data, psychiatric history and comorbidities, history of suicide attempts, history
      of substance use problems, compliance with treatment, inpatient admissions, and
      functional status. Symptom severity was assessed using the Clinical Global
      Impression-Bipolar Disorder (CGI-BP) scale, the Young Mania Rating Scale (YMRS),
      and the 5-item Hamilton Depression Rating Scale (HAMD-5). A logistic regression
      model identified baseline variables independently associated with a history of
      suicidal behavior. RESULTS: Of the 2,219 patients who provided data on their
      lifetime history of suicide attempts, 663 (29.9%) had a history of suicidal
      behavior (at least one attempt). Baseline factors associated with a history of
      suicidal behavior included female gender, a history of alcohol abuse, a history
      of substance abuse, young age at first treatment for a mood episode, longer
      disease duration, greater depressive symptom severity (HAMD-5 total score),
      current benzodiazepine use, higher overall symptom severity (CGI-BP: mania and
      overall score), and poor compliance. CONCLUSIONS: These factors may be considered
      as potential characteristics to identify subjects at risk for suicidal behavior
      throughout the course of bipolar disorder.

PMID- 21843278
TI  - The burden of obesity among adults with bipolar disorder in the United States.
AB  - OBJECTIVES: Previous studies of clinical samples of adults with bipolar disorder
      (BD) suggest that there is increased prevalence of obesity and that obesity is
      associated with greater BD severity. We therefore examined this topic in a
      representative epidemiologic sample. METHODS: The 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions was used to determine
      whether the prevalence of obesity is elevated among subjects with lifetime BD,
      and whether obesity is associated with greater severity of BD. RESULTS: The age-,
      race-, and sex-adjusted prevalence of obesity was significantly greater among
      subjects with BD versus controls [odds ratio (OR) = 1.65, 95% confidence interval
      (CI): 1.45-1.89, p < 0.001]. Obesity among subjects with BD was significantly
      positively associated with greater age, female sex, comorbid anxiety and medical
      conditions, and depression-related treatment utilization, and significantly
      negatively associated with past-year substance use disorder (SUD). In
      multivariable analyses, obesity among adults with BD was positively associated
      with age, comorbid anxiety disorders, duration of depressive episodes, and
      history of hospitalization for depression, and negatively associated with past
      year SUD. CONCLUSIONS: The increased prevalence of obesity in BD and its
      association with illness severity, particularly in relation to depression, cannot
      be attributed to biases inherent in treatment-seeking samples. Future studies are
      needed to examine the direction of the observed associations and to develop
      preventive and treatment strategies seeking to mitigate the burden of obesity in
      BD.

PMID- 21843279
TI  - Progressive neurostructural changes in adolescent and adult patients with bipolar
      disorder.
AB  - OBJECTIVES: Several lines of evidence suggest that bipolar disorder is associated
      with progressive changes in gray matter volume (GMV), particularly in brain
      structures involved in emotional regulation and expression. The majority of these
      studies however, have been cross-sectional in nature. In this study we compared
      baseline and follow-up scans in groups of bipolar disorder and healthy subjects.
      We hypothesized bipolar disorder subjects would demonstrate significant GMV
      changes over time. METHODS: A total of 58 bipolar disorder and 48 healthy
      subjects participated in structural magnetic resonance imaging (MRI). Subjects
      were rescanned 3-34 months after their baseline MRI. MRI images were segmented,
      normalized to standard stereotactic space, and compared voxel-by-voxel using
      statistical parametrical mapping software (SPM2). A model was developed to
      investigate differences in GMV at baseline, and associated with time and
      episodes, as well as in comparison to healthy subjects. RESULTS: We observed
      increases in GMV in bipolar disorder subjects across several brain regions at
      baseline and over time, including portions of the prefrontal cortex as well as
      limbic and subcortical structures. Time-related changes differed to some degree
      between adolescent and adult bipolar disorder subjects. The interval between
      scans positively correlated with GMV increases in bipolar disorder subjects in
      portions of the prefrontal cortex, and both illness duration and number of
      depressive episodes were associated with increased GMV in subcortical and limbic
      structures. CONCLUSIONS: Our findings support suggestions that widely observed
      progressive neurofunctional changes in bipolar disorder patients may be related
      to structural brain abnormalities in anterior limbic structures. Abnormalities
      largely involve regions previously noted to be integral to emotional expression
      and regulation, and appear to vary by age.

PMID- 21843280
TI  - Striatal dopamine transporter availability in unmedicated bipolar disorder.
AB  - OBJECTIVES: Dopamine transmission abnormalities have been implicated in the
      etiology of bipolar disorder (BPD). However, there is a paucity of receptor
      imaging studies in BPD, and little information is available about the dopamine
      system in BPD. Reuptake of synaptic dopamine by the dopamine transporter (DAT) is
      the principal mechanism regulating dopamine neurotransmission, and is often used
      as a marker for presynaptic dopamine function. This positron emission tomography
      (PET) study investigated whether DAT availability differed between BPD and
      healthy control subjects. METHODS: A total of 11 unmedicated BPD patients in
      either the euthymic or depressed phase and 13 closely matched healthy subjects
      underwent PET imaging with the DAT-selective radiotracer [(11) C]CFT and a
      structural magnetic resonance imaging (MRI) scan. Striatal binding potential
      (BP(ND) ) was estimated using the multilinear reference tissue model. Region of
      interest and analyses were conducted to test for differences in [(11) C]CFT
      BP(ND) between groups. RESULTS: Unmedicated BPD subjects had significantly lower
      DAT availability relative to healthy controls in bilateral dorsal caudate.
      CONCLUSIONS: The results of this study support the hypothesis that there are
      abnormalities in the dopaminergic system in BPD, and suggest that DAT
      availability may be related to the neuropathology of BPD. Future studies are
      needed to determine if DAT availability cycles with disease phase.

PMID- 21843281
TI  - Tract-specific white matter structural disruption in patients with bipolar
      disorder.
AB  - OBJECTIVES: A growing body of evidence suggests that, independent of localized
      brain lesions, mood disorders can be associated with dysfunction of brain
      networks involved in the modulation of emotional and cognitive behavior. We used
      diffusion tensor (DT) tractography to quantify the presence and extent of
      structural injury to the connections between the amygdala and other brain
      regions, which included the subgenual, the supragenual and posterior cingulate,
      the parahippocampal, the orbitofrontal and dorsolateral prefrontal cortices, as
      well as the insula. METHODS: Using a 3.0 Tesla scanner, conventional and DT
      magnetic resonance imaging sequences of the brain were acquired from 15 adult
      patients with major depressive disorder (MDD), 15 with bipolar disorder (BD), and
      21 age-matched healthy controls. Using FSL software, diffusivity changes of the
      white matter (WM) fiber bundles belonging to the emotional network were measured.
      RESULTS: Compared to controls and MDD patients, BD patients had significantly
      decreased average fractional anisotropy, increased average mean diffusivity, and
      increased average axial and radial diffusivity values in the majority of the WM
      fiber bundles connecting structures of the anterior limbic network (p-values
      ranging from 0.002 to 0.040). Medication load did not influence the results with
      the exception of lithium, which was associated with normal diffusivity values in
      tracts connecting the amygdala with the subgenual cingulate cortex. CONCLUSIONS:
      We detected specific WM abnormalities, suggestive of disrupted integrity of fiber
      bundles in the brains of patients with BD. These abnormalities might contribute
      to understanding both mood dysregulation and cognitive disturbances in BD, and
      might provide an objective marker to monitor treatment efficacy in this
      condition.

PMID- 21843282
TI  - A preliminary study of sleep in adolescents with bipolar disorder, ADHD, and non
      patient controls.
AB  - OBJECTIVES: To compare the sleep of adolescents with bipolar disorder (BD) to
      groups of adolescents with attention-deficit hyperactivity disorder-combined type
      (ADHD-C) and those without psychopathology. METHODS: A sample of 13 adolescents
      diagnosed with BD who were not in the midst of a mood episode, 14 adolescents
      with ADHD-C, and 21 healthy controls, all between the ages of 11 and 17 years
      served as participants. They were psychiatrically evaluated using a structured
      diagnostic interview and completed four nights of in-home sleep monitoring using
      actigraphy and sleep diaries. RESULTS: Sleep diary estimates of sleep indicated
      that participants with BD experienced more awakenings than their peers with ADHD,
      whereas actigraphic estimates revealed that participants with BD slept longer and
      with less wakefulness than their peers. CONCLUSIONS: In between mood episodes,
      adolescents with BD experience their sleep as more fragmented than that of their
      peers but do not exhibit more disturbed sleep as estimated by actigraphy. The
      possible influence of psychotropic medication is an important consideration when
      assessing sleep in the context of BD.

PMID- 21843283
TI  - Clinical symptoms and neurocognitive performance: potential impact of substance
      use.

PMID- 21843286
TI  - A method for control of an implantable rotary blood pump for heart failure
      patients using noninvasive measurements.
AB  - We propose a deadbeat controller for the control of pulsatile pump flow (Q(p) )
      in an implantable rotary blood pump (IRBP). Noninvasive measurements of pump
      speed and current are used as inputs to a dynamical model of Q(p) estimation,
      previously developed and verified in our laboratory. The controller was tested
      using a lumped parameter model of the cardiovascular system (CVS), in combination
      with the stable dynamical models of Q(p) and differential pressure (head)
      estimation for the IRBP. The control algorithm was tested with both constant and
      sinusoidal reference Q(p) as input to the CVS model. Results showed that the
      controller was able to track the reference input with minimal error in the
      presence of model uncertainty. Furthermore, Q(p) was shown to settle to the
      desired reference value within a finite number of sampling periods. Our results
      also indicated that counterpulsation yields the minimum left ventricular stroke
      work, left ventricular end diastolic volume, and aortic pulse pressure, without
      significantly affecting mean cardiac output and aortic pressure.

PMID- 21843287
TI  - The quest for a solution.

PMID- 21843290
TI  - Development and hydrodynamic evaluation of a novel inflow cannula in a mechanical
      circulatory support system for bridge to decision.
AB  - Recent progress in the development of implantable rotary blood pumps realized
      long-term mechanical circulatory support (MCS) for bridge to transplant, bridge
      to recovery, or a destination therapy. Meanwhile, a short-term MCS system is
      becoming necessary for bridge to decision. We developed a novel inflow cannula
      for the short-term MCS system, which gives sufficient bypass flow with minimal
      invasion at insertion, and evaluated its hydrodynamic characteristics. The novel
      inflow cannula, named the Lantern cannula, is made of elastic silicone reinforced
      with metal wires. The cannula tip has six slits on the side. This cannula tip can
      be extended to the axial direction by using an introducer and can be reduced in
      diameter, and the Lantern cannula enables easy insertion into the left ventricle
      apex with minimal invasion. The sufficient bypass flow rate can be obtained due
      to low pressure loss. Moreover, this Lantern shape also resists suction
      complication around the cannula tip. The pressure loss through the Lantern
      cannula was measured using a mock circulation and compared with two commercially
      available venous cannulae (Sarns4882, Terumo, Tokyo, Japan and Stockert V122-28,
      Sorin Group, Tokyo, Japan), which have almost same diameter as the Lantern
      cannula. Moreover, the flow patterns around the cannula tip were numerically
      analyzed by computational fluid dynamics (CFD). Acute animal experiment was also
      performed to confirm the practical effectiveness of the Lantern cannula. The
      pressure loss of the Lantern cannula was the lowest compared with those of the
      commercially available venous cannulae in in vitro experiment. CFD analysis
      results demonstrated that the Lantern cannula has low pressure loss because of
      wide inflow orifice area and a bell mouth, which were formed via Lantern shape.
      The highest bypass flow was obtained in the Lantern cannula because of the low
      pressure loss under pulsatile condition in in vivo experiments. The Lantern
      cannula demonstrated superior hydrodynamic characteristics as the inflow cannula
      in terms of pressure loss due to its specially designed Lantern shape.

PMID- 21843291
TI  - In vitro evaluation of a compliant inflow cannula reservoir to reduce suction
      events with extracorporeal rotary ventricular assist device support.
AB  - Limited preload sensitivity of rotary left ventricular assist devices (LVADs)
      renders patients susceptible to harmful atrial or ventricular suction events.
      Active control systems may be used to rectify this problem; however, they usually
      depend on unreliable sensors or potentially inaccurate inferred data from, for
      example, motor current. This study aimed to characterize the performance of a
      collapsible inflow cannula reservoir as a passive control system to eliminate
      suction events in extracorporeal, rotary LVAD support. The reservoir was
      evaluated in a mock circulation loop against a rigid cannula under conditions of
      reduced preload and increased LVAD speed in both atrial and ventricular
      cannulation scenarios. Both cases demonstrated the ease with which chamber
      suction events can occur with a rigid cannula and confirm that the addition of
      the reservoir maintained positive chamber volumes with reduced preload and high
      LVAD speeds. Reservoir performance was dependent on height with respect to the
      cannulated chamber, with lower placement required in atrial cannulation due to
      reduced filling pressures. This study concluded that a collapsible inflow cannula
      is capable of minimizing suction events in extracorporeal, rotary LVAD support.

PMID- 21843292
TI  - Intuitive use and usability of ventricular assist device peripheral components in
      simulated emergency conditions.
AB  - Ventricular assist devices (VADs) are now increasingly used to prolong the lives
      of end-stage heart failure patients. These patients vary greatly in age,
      alertness, activity, and home environment. In daily routine, but especially in
      emergencies or in conjunction with non-VAD-correlated diseases, the untrained,
      intuitive use and application of VAD peripherals by relatives, laypersons, and
      paramedics becomes important. Correct intuitive use may be a matter of life and
      death. The aim of this study was to evaluate the intuitive usability of these
      systems and to identify key features needed to optimize intuitive use. Paramedics
      (n=96) were confronted with a simulated emergency situation involving VAD
      peripherals mounted on a dummy. Three conditions were simulated: the VAD
      disconnected from its power source (n=44); both VAD batteries empty (n=44); and a
      discharged VAD battery mistakenly connected in place of a charged one (n=8). Two
      VAD systems were assessed: the Heartware HVAD and the Thoratec HeartMate II. An
      appropriate emergency card developed by our center was available in each case.
      Actions were videotaped, response times were measured, and a standardized
      questionnaire was completed after the simulation. The problem was solved by 71%
      of the participants (HVAD 83%, HMII 60%) with 87% using the emergency card. Only
      4% could solve the problem without. Cardiac massage, which was unnecessary, was
      started by 44%, while 18% complained about unnecessarily difficult conditions
      (e.g., irritation from the acoustic alarm, complexity of the emergency card,
      error-prone procedures). Better component labeling (e.g., displays, control
      elements, connectors) was recommended by 56%. A thoroughly color-coded connection
      system was especially desired. Cable- and connector-related difficulties were
      reported by 23%. The study indicated that VAD systems should be self-explaining,
      with clear labeling of components and connectors, that a clearer emergency card
      is pivotal and that similar basic handling and emergency procedures for all VAD
      types would be desirable.

PMID- 21843293
TI  - Results of animal experiments with the fourth model of the undulation pump total
      artificial heart.
AB  - Animal experiments using a total artificial heart in a goat are not easy to
      perform. The fourth model of the undulation pump total artificial heart (UPTAH4),
      which was designed to perform a long-term physiological experiment including
      pulsatile and nonpulsatile TAH operations with a conductance- and arterial
      pressure-based control method named 1/R control, was implanted in 31 goats
      weighing 38.5 to 60.4 kg (average of 46.8 kg). The 1/R control is a physiological
      flow control method of TAH developed with a conductance (1/R: reciprocal of a
      resistance) parallel circuit model. The survival periods were from 0.1 to 153
      days (average of 14.5 days). The causes of termination were postoperative
      bleeding in eight goats, respiratory failure in five goats, device failure in 14
      goats, dissected aneurysm in two goats, and thrombus in one goat. The thrombus
      case was the longest surviving goat. The respiratory failure tended to occur when
      the extracorporeal circulation time was prolonged. Autotransfusion was effective
      for the prolongation of survival time. The left-right balance control and the
      suction control were performed successfully in all goats. The 1/R control was
      performed for a long time in five goats that survived for more than 1 month. With
      three goats that survived for 48, 52, and 53 days mainly with the pulsatile mode,
      the 1/R control was stable. With a goat that survived for 73 days, the
      nonpulsatile mode with the 1/R control could be tested for 3 weeks. With the
      longest surviving goat that was maintained mainly with the pulsatile mode, the
      1/R control was unstable, possibly due to the mismatching of the response time of
      the control system between the computer and the body. However, liver and kidney
      functions were almost normal, and the total protein level recovered. Further
      study to stabilize the 1/R control in the UPTAH is necessary.

PMID- 21843294
TI  - Alterations in red blood cell volume and hemoglobin concentration, viscoelastic
      properties, and mechanical fragility caused by continuous flow pumping in calves.
AB  - In this study, we have analyzed the changes in mean corpuscular volume (MCV),
      mean corpuscular hemoglobin concentration (MCHC), and the dynamic deformability
      and mechanical fragility of red blood cells (RBCs) in five male Holstein calves
      (body weight: 95.6 +/- 10.8 kg) whose circulation was partially supported with a
      novel magnetically levitated extracorporeal centrifugal blood pump MedTech Dispo.
      One hour after the pumping has started, the MCV increased and the MCHC decreased
      by 1.064 +/- 0.006 and 0.906 +/- 0.050 times, respectively, as compared with
      those of the prepumped blood (P < 0.05). The deformability index L/W, where L and
      W are the long and short axes of the two-dimensional RBC images, respectively,
      sheared by a cyclically reversing shear flow increased indicating that the RBCs
      pumped for 1 h exhibited more elastic characteristics (P < 0.05). In addition,
      when the pumped blood cells were sheared for 30 min with a uniform shear stress
      of 25.38 Pa, the hemolysis level decreased dramatically as compared with the
      control blood, as more fragile RBCs were destroyed by pumping, leaving behind
      less fragile RBCs. All these characteristics of the RBCs exposed to continuous
      flow resemble those of young RBCs having larger MCV, lower MCHC, higher
      elasticity, and lower fragility. In conclusion, during continuous flow pumping,
      the RBCs having relatively lower threshold for hemolysis to mechanical shear
      stress generated by continuous flow blood pump (CFBP) are destroyed first and
      removed from circulation in the early stage of application of CFBP, thus leaving
      behind less fragile and stronger RBCs.

PMID- 21843295
TI  - How can we achieve infection-resistant percutaneous energy transfer?
AB  - Clinical records show ever increasing functional times of rotary blood pumps
      implanted in patients. With longer functional time, the problem of driveline
      infection is becoming more urgent. No material or scaffold has been found, which
      allows a permanent and stable ingrowth of skin cells that would prevent
      (pathogenic) germs entering the body. Usually, the epithelial cells die at the
      exit site and new cells form a sulcus around the driveline, which grows deeper
      and finally becomes infected. The purpose of this project is to present a
      solution to this problem by elaborating a new mechanism, the active skin
      penetrating device. The device is composed of a tube with a 5-mm diameter, a
      protective sleeve that surrounds the catheter exit site, and an active traction
      device. The protective sleeve is made of thin polyurethane covered with
      polyethylenterephtalat (PET, i.e. Dacron) fibers to permit the attachment of
      keratinocytes, similar to the standard driveline. The active traction device
      exerts a constant pull on the protective sleeve. The ingrown keratinocytes slowly
      give way and the protective sleeve gradually moves out of the body at a rate of a
      few millimeters per week. Meanwhile, the keratinocytes transform into horny cells
      and are then shed as in natural skin. Therefore, the formation of a sulcus is
      avoided, and the protective sleeve remains infection-free. In a first proof of
      the concept, four of the new devices and 10 control devices were implanted in
      goats. The devices remained infection-free for a period of 420 days, whereas four
      of the 10 control devices became infected. On the basis of these experiments, the
      active skin-penetrating device has been further developed and is being tested
      again in goats in a refined version. The results so far indicate that with the
      active-skin penetrating device an infection-resistant percutaneous energy
      transfer can be achieved for a prolonged period of time.

PMID- 21843296
TI  - One-month biocompatibility evaluation of the pediatric TinyPump in goats.
AB  - The TinyPump is an extracorporeal, magnetically driven centrifugal blood pump
      with its impeller suspended magnetically and hydrodynamically to provide short
      term mechanical circulatory support for children and infants. We have previously
      demonstrated that the in vivo experiments of the experimental TinyPump showed
      acceptable stable performance at pump flows averaging around 1.0 L/min with low
      hemolytic and thrombogenic properties for up to 2 weeks. We present here the 1
      month in vivo evaluation of the TinyPump, whose design was modified further for
      more durable operation. The pump was implanted as a left ventricular assist
      device in five goats (12.5-26.7 kg), with inflow inserted into the left
      ventricular apex and outflow anastomosed to the descending aorta. Five animals
      were supported for 110 pump days, with mean pump flow of 1.19 +/- 0.03 L/min at a
      pump speed of 2679 +/- 97 rpm. Two animals reached the scheduled end point of 30
      days without device failure, and mean plasma-free hemoglobin was 1.7 +/- 0.8
      mg/dL. Hematologic and biochemical data of these two animals showed no evidence
      of cardiovascular, renal, or hepatic dysfunction. Although further experiments
      are needed, the modified TinyPump offers promise as a short-term mechanical
      circulatory support device in pediatric population.

PMID- 21843297
TI  - Evaluation of hydraulic radial forces on the impeller by the volute in a
      centrifugal rotary blood pump.
AB  - In many state-of-the-art rotary blood pumps for long-term ventricular assistance,
      the impeller is suspended within the casing by magnetic or hydrodynamic means.
      For the design of such suspension systems, profound knowledge of the acting
      forces on the impeller is crucial. Hydrodynamic bearings running at low clearance
      gaps can yield increased blood damage and magnetic bearings counteracting high
      forces consume excessive power. Most current rotary blood pump devices with
      contactless bearings are centrifugal pumps that incorporate a radial diffuser
      volute where hydraulic forces on the impeller develop. The yielding radial forces
      are highly dependent on impeller design, operating point and volute design. There
      are three basic types of volute design--singular, circular, and double volute. In
      this study, the hydraulic radial forces on the impeller created by the volute in
      an investigational centrifugal blood pump are evaluated and discussed with regard
      to the choice of contactless suspension systems. Each volute type was tested
      experimentally in a centrifugal pump test setup at various rotational speeds and
      flow rates. For the pump's design point at 5 L/min and 2500 rpm, the single
      volute had the lowest radial force (~0 N), the circular volute yielded the
      highest force (~2 N), and the double volute possessed a force of approx. 0.5 N.
      Results of radial force magnitude and direction were obtained and compared with a
      previously performed computational fluid dynamics (CFD) study.

PMID- 21843299
TI  - Characterization of 215 simple sequence repeat markers in creeping bentgrass
      (Agrostis stolonifera L.).
AB  - Creeping bentgrass (Agrostis stolonifera L.) is a versatile, cross-pollinated,
      temperate and perennial turfgrass species. It occurs naturally in a wide variety
      of habitats and is also cultivated on golf courses, bowling greens and tennis
      courts worldwide. Isozymes and amplified fragment length polymorphisms (AFLPs)
      have been used to determine genetic diversity, and restriction fragment length
      polymorphisms (RFLPs) and random amplified polymorphic DNA (RAPDs) were used to
      construct a genetic linkage map of this species. In the current report, we
      developed and characterized 215 unique genomic simple sequence repeat (SSR)
      markers in creeping bentgrass. The SSRs reported here are the first available
      markers in creeping bentgrass to date. Eight hundred and eighteen alleles were
      amplified by 215 SSR loci, an average of 3.72 alleles per locus. Fifty-nine per
      cent of those alleles segregated in a 1:1 Mendelian fashion (P > 0.05). Twenty
      two per cent had a distorted segregation ratio (P <= 0.05). These SSR markers
      will be useful for assessing genetic diversity in creeping bentgrass and will be
      important for the development of genetic linkage maps and identifying
      quantitative trait loci. These markers could enhance breeding programmes by
      improving the efficiency of selection techniques.

PMID- 21843300
TI  - The message for MODY.

PMID- 21843302
TI  - Disturbed vibrotactile sense in finger pulps in patients with Type 1 diabetes-
      correlations with glycaemic level, clinical examination and electrophysiology.
AB  - AIMS: In a cohort of men and women with Type 1 diabetes, prospectively followed
      for > 20 years, vibrotactile sense in fingers was investigated and related to
      neurophysiological tests, glycaemic level and clinical score. METHODS: Out of 58
      patients, diagnosed at the age of 15-25 years and recruited 1984-1985, 32
      patients (13 women, median age 52 years, range 44-75 years; 19 men, median age 52
      years, range 39-69 years; median duration 33.5 years, range 21-52 years) accepted
      follow-up in 2006. Vibration thresholds were measured in finger pulps of index
      and little fingers bilaterally at seven frequencies and related to results of
      touch (monofilaments), tactile discrimination (two-point discrimination test),
      electrophysiology (median nerve function), glycaemic level (HbA(1c) levels since
      1984-1985) and a clinical score. RESULTS: Vibrotactile sense was reduced in
      finger pulps, mainly in men, compared with an age- and gender-matched healthy
      control group with normal HbA(1c) . Vibration thresholds were increased,
      particularly at 250 and 500 Hz, in both index and little finger pulps. Touch and
      tactile discrimination correlated with vibration thresholds, but not with each
      other or with electrophysiology. HbA(1c) levels (at follow-up or mean values from
      five follow-ups since recruitment) did not correlate with any nerve function
      variables. Clinical scores correlated with vibrotactile sense, particularly at
      higher frequencies (> 125 Hz), but not with total Z-scores of electrophysiology.
      Duration of disease did not correlate with any variables. CONCLUSIONS:
      Examination of vibration thresholds in index and little finger pulps may be
      valuable to detect neuropathy, where thresholds correlate with symptoms and
      tests.

PMID- 21843301
TI  - Urine C-peptide creatinine ratio is an alternative to stimulated serum C-peptide
      measurement in late-onset, insulin-treated diabetes.
AB  - AIMS: Serum C-peptide measurement can assist clinical management of diabetes, but
      practicalities of collection limit widespread use. Urine C-peptide creatinine
      ratio may be a non-invasive practical alternative. The stability of C-peptide in
      urine allows outpatient or community testing. We aimed to assess how urine C
      peptide creatinine ratio compared with serum C-peptide measurement during a mixed
      meal tolerance test in individuals with late-onset, insulin-treated diabetes.
      METHODS: We correlated the gold standard of a stimulated serum C-peptide in a
      mixed-meal tolerance test with fasting and stimulated (mixed-meal tolerance test,
      standard home meal and largest home meal) urine C-peptide creatinine ratio in 51
      subjects with insulin-treated diabetes (diagnosis after age 30 years, median age
      66 years, median age at diagnosis 54, 42 with Type 2 diabetes, estimated
      glomerular filtration rate > 60 ml min(-1) 1.73 m(-2) ). RESULTS: Ninety-minute
      mixed-meal tolerance test serum C-peptide is correlated with mixed-meal tolerance
      test-stimulated urine C-peptide creatinine ratio (r = 0.82), urine C-peptide
      creatinine ratio after a standard breakfast at home (r = 0.73) and urine C
      peptide creatinine ratio after largest home meal (r = 0.71). A stimulated
      (largest home meal) urine C-peptide creatinine ratio cut-off of 0.3 nmol/mmol had
      a 100% sensitivity and 96% specificity (area under receiver operating
      characteristic curve = 0.99) in identifying subjects without clinically
      significant endogenous insulin secretion (mixed-meal tolerance test-stimulated C
      peptide < 0.2 nmol/l). In detecting a proposed serum C-peptide threshold for
      insulin requirement (stimulated serum C-peptide < 0.6 nmol/l), a stimulated
      (largest home meal) urine C-peptide creatinine ratio cut-off of 0.6 nmol/mmol had
      a sensitivity and specificity of 92%. CONCLUSION: In patients with insulin
      treated diabetes diagnosed after age 30 years, urine C-peptide creatinine ratio
      is well correlated with serum C-peptide and may provide a practical alternative
      measure to detect insulin deficiency for use in routine clinical practice.

PMID- 21843303
TI  - Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2
      diabetes: influences of glycaemic control, obesity and social disadvantage.
AB  - AIMS: To compare obstetric and perinatal outcomes in women with Type 1 and Type 2
      diabetes and relate these to maternal risk factors. METHODS: Prospective cohort
      study of 682 consecutive diabetic pregnancies in East Anglia during 2006-2009.
      Relationships between congenital malformation, perinatal mortality and perinatal
      morbidity (large for gestational age, preterm delivery, neonatal care) with
      maternal age, parity, ethnicity, glycaemic control, obesity and social
      disadvantage were examined using bivariable and multivariate models. RESULTS:
      There were 408 (59.8%) Type 1 and 274 (40.2%) Type 2 diabetes pregnancies. Women
      with Type 2 diabetes were older (P < 0.001), heavier (P < 0.0001), more
      frequently multiparous (P < 0.001), more ethnically diverse (p < 0.0001) and more
      socially disadvantaged (P = 0.0004). Although women with Type 2 diabetes had
      shorter duration of diabetes (P < 0.0001) and better pre-conception glycaemic
      control [HbA(1c) 52 mmol/mol (6.9%) Type 2 diabetes vs. 63 mmol/l (7.9%) Type 1
      diabetes; p < 0.0001), rates of congenital malformation and perinatal mortality
      were comparable. Women with Type 2 diabetes had fewer large-for-gestational-age
      infants (37.6 vs. 52.9%, P < 0.0008), fewer preterm deliveries (17.5 vs. 37.1%, P
      < 0.0001) and their offspring had fewer neonatal care admissions (29.8 vs. 43.2%,
      P = 0.001). Third trimester HbA(1c) (OR 1.35, 95% CI 1.09-1.67, P = 0.006) and
      social disadvantage (OR 0.80, 95% CI 0.67-0.98; P = 0.03) were risk factors for
      large for gestational age. CONCLUSIONS: Despite increased age, parity, obesity
      and social disadvantage, women with Type 2 diabetes had better glycaemic control,
      fewer large-for-gestational-age infants, fewer preterm deliveries and fewer
      neonatal care admissions. Better tools are needed to improve glycaemic control
      and reduce the rates of large for gestational age, particularly in Type 1
      diabetes.

PMID- 21843304
TI  - The Finnish Diabetes Risk Score is associated with insulin resistance but not
      reduced beta-cell function, by classical and model-based estimates.
AB  - AIMS: The Finnish Diabetes Risk Score (FINDRISC) is widely used for risk
      stratification in Type 2 diabetes prevention programmes. Estimates of beta-cell
      function vary widely in people without diabetes and reduced insulin secretion has
      been described in people at risk for diabetes. The aim of this analysis was to
      evaluate FINDRISC as a tool to characterize reduced beta-cell function in
      individuals without known diabetes. METHODS: In this population-based cohort from
      the Hoorn municipal registry, subjects received an oral glucose tolerance test
      and a meal tolerance test on separate days, in random order, within 2 weeks. One
      hundred and eighty-six subjects, age 41-66 years, with no known Type 2 diabetes
      were included. Of those, 163 (87.6%) had normal glucose metabolism and 23 (12.4%)
      had abnormal glucose metabolism (19 with impaired glucose metabolism; four with
      newly diagnosed Type 2 diabetes based on study results). Insulin sensitivity and
      beta-cell function (classical: insulinogenic index; ratio of areas under
      insulin/glucose curves; model-based: glucose sensitivity; rate sensitivity;
      potentiation) estimates were calculated from oral glucose tolerance test and meal
      tolerance test data. RESULTS: FINDRISC was associated with insulin sensitivity (r
      = -0.41, P < 0.0001), insulin/glucose areas under the curve (meal tolerance test:
      r = 0.29, P < 0.0001; oral glucose tolerance test: r = 0.21, P = 0.01) and
      potentiation factor (meal tolerance test: r = 0.21, P = 0.01). After adjusting
      for insulin sensitivity, these associations with beta-cell function were no
      longer significant. CONCLUSIONS: After adjustment for insulin sensitivity,
      FINDRISC was not associated with reduced beta-cell function in subjects without
      known Type 2 diabetes. While insulin secretion and insulin sensitivity are both
      components in Type 2 diabetes development, insulin sensitivity appears to be the
      dominant component behind the association between FINDRISC and diabetes risk.

PMID- 21843305
TI  - Initiation of insulin glargine in patients with Type 2 diabetes in suboptimal
      glycaemic control positively impacts health-related quality of life. A
      prospective cohort study in primary care.
AB  - AIMS: To study prospectively the impact of initiating insulin glargine in
      suboptimally controlled insulin-naive patients with Type 2 diabetes on health
      related quality of life in relation to glycaemic control. METHODS: Insulin-naive
      Dutch patients with Type 2 diabetes in suboptimal glycaemic control (HbA(1c) > 53
      mmol/mol; 7%) on maximum dose of oral glucose-lowering medications were included
      from 363 primary care practices (n = 911). Patients started insulin glargine and
      were followed up for 6 months. At baseline (start insulin therapy), 3 and 6
      months, HbA(1c) was measured and patients completed self-report health-related
      quality of life measures, including emotional well-being (World Health
      Organization-5 well-being index), fear of hypoglycaemia (Hypoglycaemia Fear
      Survey) and diabetes symptom distress (Diabetes Symptom Checklist-revised). Data
      were analysed using generalized estimating equations analysis. RESULTS: HbA(1c)
      (mmol/mol; %) decreased from 69 +/- 16; 8.5 +/- 1.7 to 60 +/- 11; 7.6 +/- 1.0 and
      57 +/- 11; 7.3 +/- 1.0 at 3 and 6 months, respectively (P < 0.001). Pre-insulin
      BMI (kg/m(2) ) was 30 +/- 5.7, which remained stable at 3 months (30 +/- 5.8) and
      increased to 31 +/- 5.9 at 6 months (P = 0.004); no significant changes in self
      reported symptomatic and severe hypoglycaemia were observed, while nocturnal
      hypoglycaemia slightly decreased. The Hypoglycaemia Fear Survey score decreased
      from 14.6 +/- 16.2 to 12.1 +/- 15.2 and 10.8 +/- 14.4 at 3 and 6 months,
      respectively (P < 0.001). The Diabetes Symptom Checklist-revised score decreased
      from 15 +/- 14 to 10 +/- 12 and 10 +/- 13 (P < 0.001), with most pronounced
      reductions in hyperglycaemic symptoms and fatigue. The World Health Organization
      5 score increased from 57 +/- 25.3 to 65 +/- 21.6 at 3-month follow-up and 67 +/-
      21.8 at 6-month follow-up (P < 0.001). CONCLUSIONS: Results of this observational
      study demonstrate combined glycaemic and health-related quality of life benefits
      of initiating insulin glargine in patients with Type 2 diabetes in routine
      primary care.

PMID- 21843306
TI  - Behaviour and metabolic control in children with Type 1 diabetes mellitus on
      insulin pump therapy: 2-year follow-up.
AB  - AIMS: This study investigated whether continuous subcutaneous insulin infusion is
      associated with sustained improvement in behaviour and metabolic control.
      METHODS: Children with Type 1 diabetes mellitus (n = 27, 8-18 years old) who had
      been assessed previously prior to commencing continuous subcutaneous insulin
      infusion, and 6-8 weeks later, were re-evaluated 2 years after commencing insulin
      pump therapy. Behaviour was reassessed using the Behavioral Assessment System for
      Children-2nd edition (BASC-2) and current HbA(1c) levels were recorded. RESULTS:
      Two years after commencing continuous subcutaneous insulin infusion, parent
      reported internalizing and externalizing symptoms were significantly lower than
      pre-insulin pump therapy commencement levels. Self reports of internalizing and
      externalizing problems did not differ significantly across the three assessment
      points. There was no significant difference between pre-insulin pump therapy
      HbA(1c) and HbA(1c) after 2 years on continuous subcutaneous insulin infusion,
      despite an initial improvement 6-8 weeks after commencing the therapy.
      CONCLUSIONS: Children with Type 1 diabetes mellitus showed sustained improvements
      in parent-reported behaviour, but not in self reports of behaviour or in
      metabolic control 2 years after commencement of continuous subcutaneous insulin
      infusion.

PMID- 21843307
TI  - Validation of an abbreviated adherence measure for young people with Type 1
      diabetes.
AB  - AIMS: Adherence to diabetes-related tasks is an important construct. The Diabetes
      Self-Management Profile is a validated, semi-structured interview assessing
      adherence in paediatric patients with Type 1 diabetes. We created and validated a
      brief questionnaire version of the Diabetes Self-Management Profile called the
      Diabetes Self-Management Questionnaire. METHODS: Young people with Type 1
      diabetes, ages 9-15 years (n = 338) and their parents provided data from chart
      review, interview and questionnaires. RESULTS: Diabetes Self-Management
      Questionnaire scores correlated significantly with Diabetes Self-Management
      Profile scores, HbA(1c) , blood glucose monitoring frequency and other measures
      associated with adherence and/or glycaemic control (P <= 0.01 for all). Young
      people and parent scores were correlated (r = 0.55, P < 0.0001). The Diabetes
      Self-Management Questionnaire demonstrated modest internal consistency
      (Cronbach's alpha = 0.59), adequate for a brief measure of multidimensional
      adherence. In addition, factor analysis confirmed one factor. CONCLUSIONS: This
      brief adherence questionnaire demonstrated construct validity in young people 9
      15 years old and their parents and may have utility in clinical and research
      settings.

PMID- 21843308
TI  - Economic impact of moderate weight loss in patients with Type 2 diabetes: the
      Fremantle Diabetes Study.
AB  - AIM: To assess the change in the cost of diabetes medication attributable to
      moderate weight loss in patients with Type 2 diabetes. METHODS: Longitudinal data
      collected annually from 590 patients participating in the observational,
      community-based Fremantle Diabetes Study were examined to determine whether
      moderate weight loss (>= 5% of initial body weight) was independently associated
      with diabetes medication cost during 4 years' follow-up. RESULTS: Overall, the
      weight of the cohort decreased significantly during 4.3 +/- 0.4 years' follow-up
      by 1.3 +/- 6.2 kg (-1.4 +/- 7.9% baseline body weight; trend P < 0.001). Moderate
      weight loss was achieved by 31%. HbA(1c) improved significantly in the group with
      moderate weight loss compared with the group without moderate weight loss [-4 +/-
      16 mmol/mol (-0.3 +/- 1.5%) vs. 0 +/- 17 mmol/mol (0.0 +/- 1.5%), P = 0.015].
      Mean (bias-corrected 95% confidence intervals) diabetes medication costs were
      $A820 ($A744-907) during follow-up. As the cost distribution was highly right
      skewed and contained zeros, it was square root (?) transformed before multiple
      linear regression analysis. The most parsimonious model of baseline associates of
      ?(diabetes medication cost) included glycaemic control, diabetes treatment,
      diabetes duration, BMI, systolic blood pressure, serum HDL cholesterol
      (negative), taking lipid-lowering medication and age (negative) (adjusted R(2) =
      73.6%). After adjusting for these variables, ?(diabetes medication cost) was
      negatively associated with moderate weight loss (P = 0.026). After entering
      average values for the cohort into the model, the cost of diabetes medications
      between baseline and fourth review for an average patient with no weight loss was
      $A752 compared with $A652 for a patient who attained moderate weight loss, a
      saving of $A100 (-13.3%). DISCUSSION: These data highlight the economic and
      clinical benefits of moderate weight loss in Type 2 diabetes.

PMID- 21843309
TI  - The Caulobacter crescentus chromosome replication origin evolved two classes of
      weak DnaA binding sites.
AB  - The Caulobacter crescentus replication initiator DnaA and essential response
      regulator CtrA compete to control chromosome replication. The C. crescentus
      replication origin (Cori) contains five strong CtrA binding sites but only two
      apparent DnaA boxes, termed G-boxes (with a conserved second position G,
      TGATCCACA). Since clusters of DnaA boxes typify bacterial replication origins,
      this discrepancy suggested that C. crescentus DnaA recognizes different DNA
      sequences or compensates with novel DNA-binding proteins. We searched for novel
      DNA sites by scanning mutagenesis of the most conserved Cori DNA. Autonomous
      replication assays showed that G-boxes and novel W-boxes (TCCCCA) are essential
      for replication. Further analyses showed that C. crescentus DnaA binds G-boxes
      with moderate and W-boxes with very weak affinities significantly below DnaA's
      capacity for high-affinity Escherichia coli-boxes (TTATCCACA). Cori has five
      conserved W-boxes. Increasing W-box affinities increases or decreases autonomous
      replication depending on their strategic positions between the G-boxes. In vitro,
      CtrA binding displaces DnaA from proximal G-boxes and from distal W-boxes
      implying CtrA-DnaA competition and DnaA-DnaA cooperation between G-boxes and W
      boxes. Similarly, during cell cycle progression, CtrA proteolysis coincides with
      DnaA binding to Cori. We also observe highly conserved W-boxes in other
      replication origins lacking E. coli-boxes. Therefore, strategically weak DnaA
      binding can be a general means of replication control.

PMID- 21843310
TI  - Anomalous diffusion imposed by dendritic spines (Commentary on Santamaria et
      al.).

PMID- 21843311
TI  - Primary parotid gland lymphoma: a case report.
AB  - INTRODUCTION: Mucosa associated lymphoid tissue lymphomas are the most common
      lymphomas of the salivary glands. The benign lymphoepithelial lesion is also a
      lymphoproliferative disease that develops in the parotid gland. In the present
      case report, we describe one case of benign lymphoepithelial lesion with a
      subsequent low transformation to grade mucosa associated lymphoid tissue lymphoma
      appearing as a cystic mass in the parotid gland. CASE PRESENTATION: A 78-year-old
      Caucasian female smoker was referred to our clinic with a non-tender left facial
      swelling that had been present for approximately three years. The patient
      underwent resection of the left parotid gland with preservation of the left
      facial nerve through a preauricular incision. The pathology report was consistent
      with a low-grade marginal-zone B-cell non-Hodgkin lymphoma (mucosa associated
      lymphoid tissue lymphoma) following benign lymphoepithelial lesion of the gland.
      CONCLUSIONS: Salivary gland mucosa associated lymphoid tissue lymphoma should be
      considered in the differential diagnosis of cystic or bilateral salivary gland
      lesions. Parotidectomy is recommended in order to treat the tumor and to ensure
      histological diagnosis for further follow-up planning. Radiotherapy and
      chemotherapy should be considered in association with surgery in disseminated
      forms or after removal.

PMID- 21843312
TI  - Downregulation of CDKN2A and suppression of cyclin D1 gene expressions in
      malignant gliomas.
AB  - BACKGROUND: Malignant gliomas are the most common in central nervous system
      cancer. Genome-wide association study identifies that CDKN2A was a susceptibility
      loci for glioma. The CDKN2A/cyclin-dependent kinase 4, 6/Retinoblastoma protein
      (Rb) pathway is thought to play a crucial role in malignant gliomas pathogenesis.
      We have investigated the expression of CDKN2A for potential correlations with
      malignant gliomas grade and potential role of CDKN2A on malignant gliomas
      pathogenesis. METHODS: Tumour tissue samples from 61 patients suffering from
      malignant gliomas were investigated. The expression levels of CDKN2A were
      detected using immunohistochemical staining and western blot. Overexpression and
      knockdown of CDKN2A were performed in human glioma cell lines. Subsequently,
      colony formation, growth curves and CDKN2A-Cyclin-Rb pathway were analyzed.
      RESULTS: Here we show that a lower expression of CDKN2A and a higher expression
      of cyclin D1 in the patients with high-grade malignant gliomas than low-grade
      gliomas, respectively. Moreover, overexpression of CDKN2A inhibits growth of
      glioma cell lines by suppression of cyclin D1 gene expression. CONCLUSIONS: Our
      study suggests that CDKN2A as a malignant gliomas suppressor gene, appears to be
      useful for predicting behaviour of high-grade malignant gliomas. CDKN2A-Cyclin-Rb
      pathway plays a key role on malignant gliomas formation and that therapeutic
      targeting of this pathway may be useful in malignant gliomas treatment.

PMID- 21843313
TI  - Use of electronic personal health record systems to encourage HIV screening: an
      exploratory study of patient and provider perspectives.
AB  - BACKGROUND: When detected, HIV can be effectively treated with antiretroviral
      therapy. Nevertheless in the U.S. approximately 25% of those who are HIV-infected
      do not know it. Much remains unknown about how to increase HIV testing rates. New
      Internet outreach methods have the potential to increase disease awareness and
      screening among patients, especially as electronic personal health records (PHRs)
      become more widely available. In the US Department of Veterans' Affairs medical
      care system, 900,000 veterans have indicated an interest in receiving electronic
      health-related communications through the PHR. Therefore we sought to evaluate
      the optimal circumstances and conditions for outreach about HIV screening. In an
      exploratory, qualitative research study we examined patient and provider
      perceptions of Internet-based outreach to increase HIV screening among veterans
      who use the Veterans Health Administration (VHA) health care system. FINDINGS: We
      conducted two rounds of focus groups with veterans and healthcare providers at
      VHA medical centers. The study's first phase elicited general perceptions of an
      electronic outreach program to increase screening for HIV, diabetes, and high
      cholesterol. Using phase 1 results, outreach message texts were drafted and then
      presented to participants in the second phase. Analysis followed modified
      grounded theory.Patients and providers indicated that electronic outreach through
      a PHR would provide useful information and would motivate patients to be screened
      for HIV. Patients believed that electronic information would be more convenient
      and understandable than information provided verbally. Patients saw little
      difference between messages about HIV versus about diabetes and cholesterol.
      Providers, however, felt patients would disapprove of HIV-related messages due to
      stigma. Providers expected increased workload from the electronic outreach, and
      thus suggested adding primary care resources and devising methods to smooth the
      flow of patients getting screened. When provided a choice between unsecured
      emails versus PHRs as the delivery mechanism for disease screening messages, both
      patients and providers preferred PHRs. CONCLUSIONS: There is considerable
      potential to use PHR systems for electronic outreach and social marketing to
      communicate to patients about, and increase rates of, disease screening,
      including for HIV. Planning for direct-to-patient communications through PHRs
      should include providers and address provider reservations, especially about
      workload increases.

PMID- 21843314
TI  - HIF-1alpha effects on angiogenic potential in human small cell lung carcinoma.
AB  - BACKGROUND: Hypoxia-inducible factor-1 alpha (HIF-1alpha) maybe an important
      regulatory factor for angiogenesis of small cell lung cancer (SCLC). Our study
      aimed to investigate the effect of HIF-1alpha on angiogenic potential of SCLC
      including two points: One is the effect of HIF-1alpha on the angiogenesis of SCLC
      in vivo. The other is the regulation of angiogenic genes by HIF-1alpha in vitro
      and in vivo. METHODS: In vivo we used an alternative method to study the effect
      of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell
      transplantation tumor on the chick embryo chorioallantoic membrane (CAM) surface.
      In vitro we used microarray to screen out the angiogenic genes regulated by HIF
      1a and tested their expression level in CAM transplantation tumor by RT-PCR and
      Western-blot analysis. RESULTS: In vivo angiogenic response surrounding the SCLC
      transplantation tumors in chick embryo chorioallantoic membrane (CAM) was
      promoted after exogenous HIF-1alpha transduction (p < 0.05). In vitro the changes
      of angiogenic genes expression induced by HIF-1alpha in NCI-H446 cells were
      analyzed by cDNA microarray experiments. HIF-1alpha upregulated the expression of
      angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26
      , 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98
      , 3.74- fold respectively. In addition, the expression of these angiogenic
      factors were also upregulated by HIF-1alpha in the transplantion tumors in CAM as
      RT-PCR and Western-blot analysis indicated. CONCLUSIONS: These results indicated
      that HIF-1alpha may enhance the angiogenic potential of SCLC by regulating some
      angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1alpha may be a
      potential target for the gene targeted therapy of SCLC.

PMID- 21843315
TI  - Computational archaeology of the Pristionchus pacificus genome reveals evidence
      of horizontal gene transfers from insects.
AB  - BACKGROUND: The recent sequencing of nematode genomes has laid the basis for
      comparative genomics approaches to study the impact of horizontal gene transfer
      (HGT) on the adaptation to new environments and the evolution of parasitism. In
      the beetle associated nematode Pristionchus pacificus HGT events were found to
      involve cellulase genes of microbial origin and Diapausin genes that are known
      from beetles, but not from other nematodes. The insect-to-nematode horizontal
      transfer is of special interest given that P. pacificus shows a tight association
      with insects. RESULTS: In this study we utilized the observation that
      horizontally transferred genes often exhibit codon usage patterns more similar to
      that of the donor than that of the acceptor genome. We introduced GC-normalized
      relative codon frequencies as a measure to detect characteristic features of P.
      pacificus orphan genes that show no homology to other nematode genes. We found
      that atypical codon usage is particularly prevalent in P. pacificus orphans. By
      comparing codon usage profiles of 71 species, we detected the most significant
      enrichment in insect-like codon usage profiles. In cross-species comparisons, we
      identified 509 HGT candidates that show a significantly higher similarity to
      insect-like profiles than genes with nematode homologs. The most abundant gene
      family among these genes are non-LTR retrotransposons. Speculating that
      retrotransposons might have served as carriers of foreign genetic material, we
      found a significant local clustering tendency of orphan genes in the vicinity of
      retrotransposons. CONCLUSIONS: Our study combined codon usage bias, phylogenetic
      analysis, and genomic colocalization into a general picture of the computational
      archaeology of the P. pacificus genome and suggests that a substantial fraction
      of the gene repertoire is of insect origin. We propose that the Pristionchus
      beetle association has facilitated HGT and discuss potential vectors of these
      events.

PMID- 21843316
TI  - Orthoretroviral-like prototype foamy virus Gag-Pol expression is compatible with
      viral replication.
AB  - BACKGROUND: Foamy viruses (FVs) unlike orthoretroviruses express Pol as a
      separate precursor protein and not as a Gag-Pol fusion protein. A unique
      packaging strategy, involving recognition of briding viral RNA by both Pol
      precursor and Gag as well as potential Gag-Pol protein interactions, ensures Pol
      particle encapsidation. RESULTS: Several Prototype FV (PFV) Gag-Pol fusion
      protein constructs were generated to examine whether PFV replication is
      compatible with an orthoretroviral-like Pol expression. During their analysis,
      non-particle-associated secreted Pol precursor protein was discovered in
      extracellular wild type PFV particle preparations of different origin,
      copurifying in simple virion enrichment protocols. Different analysis methods
      suggest that extracellular wild type PFV particles contain predominantly mature
      p85(PR-RT) and p40(IN) Pol subunits. Characterization of various PFV Gag-Pol
      fusion constructs revealed that PFV Pol expression in an orthoretroviral manner
      is compatible with PFV replication as long as a proteolytic processing between
      Gag and Pol proteins is possible. PFV Gag-Pol translation by a HIV-1 like
      ribosomal frameshift signal resulted in production of replication-competent
      virions, although cell- and particle-associated Pol levels were reduced in
      comparison to wild type. In-frame fusion of PFV Gag and Pol ORFs led to increased
      cellular Pol levels, but particle incorporation was only marginally elevated.
      Unlike that reported for similar orthoretroviral constructs, a full-length in
      frame PFV Gag-Pol fusion construct showed wildtype-like particle release and
      infectivity characteristics. In contrast, in-frame PFV Gag-Pol fusion with C
      terminal Gag ORF truncations or non-removable Gag peptide addition to Pol
      displayed wildtype particle release, but reduced particle infectivity. PFV Gag
      Pol precursor fusion proteins with inactivated protease were highly deficient in
      regular particle release, although coexpression of p71(Gag) resulted in a
      significant copackaging of these proteins. CONCLUSIONS: Non-particle associated
      PFV Pol appears to be naturally released from infected cells by a yet unknown
      mechanism. The absence of particle-associated Pol precursor suggests its rapid
      processing upon particle incorporation. Analysis of different PFV Gag-Pol fusion
      constructs demonstrates that orthoretroviral-like Pol expression is compatible
      with FV replication in principal as long as fusion protein processing is
      possible. Furthermore, unlike orthoretroviruses, PFV particle release and
      infectivity tolerate larger differences in relative cellular Gag/Pol levels.

PMID- 21843317
TI  - Selection of hepatitis C virus resistant to ribavirin.
AB  - BACKGROUND: Given the side effects associated with intravenous injections of
      interferon, an interferon-free regimen for the treatment of HCV infections is
      highly desirable. Recently published clinical studies show that interferon-free
      combination therapies containing ribavirin are efficacious, suggesting that an
      interferon-free therapy could be adopted in the near future. Therefore,
      understanding HCV resistance to ribavirin could be of major importance. In an
      approach to understand the effect of ribavirin on HCV replication and HCV
      resistance, we have selected a ribavirin resistant mutant of HCV in vitro.
      METHODS: We serially passed the J6/JFH1 strain of HCV in Huh7D cells (a Huh7 cell
      derivative more permissive to HCV replication) in the presence of different
      concentrations of ribavirin. Virus replication was assessed by detection of HCV
      antigens by immunfluorscence of infected cells and titration of recovered virus
      present in the supernatant. cDNAs from virus RNA grown in 0 or 250 uM
      concentrations of ribavirin were synthesized by RT-PCR, and sequenced. RESULTS: A
      concentration of 125 uM of ribavirin did not have a dramatic effect on HCV
      replication, while 500 uM of ribavirin lead to viral extinction. Concentrations
      of 250 uM of ribavirin dramatically reduced virus replication which was sustained
      over six passages. At passage seven viral resurgence began and over two passages
      the level of virus reached that of the wild type virus grown without ribavirin.
      Virus recovered from these cultures were more resistant to 250 uM ribavirin than
      wild type virus, and showed no difference in replication relative to wild type
      virus when grown in the absence of ribavirin. The ribavirin resistant virus
      accumulated multiple synonymous and non-synonymous mutations that are presently
      being analyzed for their relationship to ribavirin resistance. CONCLUSIONS: It is
      possible to select a ribavirin resistant mutant of HCV that can replicate to
      levels similar to wild type virus grown without ribavirin. Analysis of the
      mutations responsible for the ribavirin resistance may aid in understanding the
      mechanism of action of ribavirin.

PMID- 21843319
TI  - Full recovery of a 13-year-old boy with pediatric Ramsay Hunt syndrome using a
      shorter course of aciclovir and steroid at lower doses: a case report.
AB  - INTRODUCTION: Reports on children with Ramsay Hunt syndrome are limited in the
      literature, resulting in uncertainty regarding the clinical manifestations and
      outcome of this syndrome. Treatment for Ramsay Hunt syndrome is usually with
      antivirals, although there is no evidence for beneficial effect on the outcome of
      Ramsay Hunt syndrome in adults (insufficient data on children exists). Here, we
      report a case of Ramsay Hunt syndrome occurring in a child who inadvertently
      received a lower dose of aciclovir and steroid administered for shorter than is
      usual. Our patient made a full recovery. CASE PRESENTATION: A 13-year-old African
      boy presented to our out-patients department with an inability to move the right
      side of his face for one week. He had previously been seen by the doctor on call,
      who prescribed aciclovir 200 mg three times per day and prednisone 20 mg once
      daily, both orally for five days, with a working diagnosis of Bell's palsy. After
      commencement of aciclovir-prednisone, while at home, our patient had headache,
      malaise, altered taste, vomiting after feeds, a ringing sound in his right ear as
      well as earache and ear itchiness. Additionally, he developed numerous fluid
      filled pimples on his right ear. On presentation, a physical examination revealed
      a right-sided lower motor neuron facial nerve palsy and a healing rash on the
      right pinna. On direct questioning, our patient admitted having had chicken pox
      about three months previously. Based on the history and physical examination,
      Ramsay Hunt syndrome was diagnosed. Our patient was lost to follow-up until 11
      months after the onset of illness; at this time, his facial nerve function was
      normal. CONCLUSIONS: This case report documents the clinical manifestations and
      outcome of pediatric Ramsay Hunt syndrome; a condition with few case reports in
      the literature. In addition, our patient made a full recovery despite
      inadvertently receiving a lower dose of aciclovir and steroid administered for
      shorter than is usual.

PMID- 21843318
TI  - Genotypic and functional properties of early infant HIV-1 envelopes.
AB  - BACKGROUND: Understanding the properties of HIV-1 variants that are transmitted
      from women to their infants is crucial to improving strategies to prevent
      transmission. In this study, 162 full-length envelope (env) clones were generated
      from plasma RNA obtained from 5 HIV-1 Clade B infected mother-infant pairs.
      Following extensive genotypic and phylogenetic analyses, 35 representative clones
      were selected for functional studies. RESULTS: Infant quasispecies were highly
      homogeneous and generally represented minor maternal variants, consistent with
      transmission across a selective bottleneck. Infant clones did not differ from the
      maternal in env length, or glycosylation. All infant variants utilized the CCR5
      co-receptor, but were not macrophage tropic. Relatively high levels (IC50 >= 100
      MUg/ml) of autologous maternal plasma IgG were required to neutralize maternal
      and infant viruses; however, all infant viruses were neutralized by pooled sera
      from HIV-1 infected individuals, implying that they were not inherently
      neutralization-resistant. All infant viruses were sensitive to the HIV-1 entry
      inhibitors Enfuvirtide and soluble CD4; none were resistant to Maraviroc.
      Sensitivity to human monoclonal antibodies 4E10, 2F5, b12 and 2G12 varied.
      CONCLUSIONS: This study provides extensive characterization of the genotypic and
      functional properties of HIV-1 env shortly after transmission. We present the
      first detailed comparisons of the macrophage tropism of infant and maternal env
      variants and their sensitivity to Maraviroc, the only CCR5 antagonist approved
      for therapeutic use. These findings may have implications for improving
      approaches to prevent mother-to-child HIV-1 transmission.

PMID- 21843320
TI  - Lobar pneumonia caused by Ralstonia pickettii in a sixty-five-year-old Han
      Chinese man: a case report.
AB  - INTRODUCTION: Ralstonia pickettii is a gram-negative, oxidase-positive bacillus
      and is an emerging pathogen found in infections described in hospital settings.
      The cases reported in the literature mostly are nosocomial infections due to
      contaminated blood products, sterile water, saline, treatment fluids and venous
      catheters. Human infection unrelated to contaminated solutions is rare. We report
      a case of lobar pneumonia and pulmonary abscess caused by Ralstonia pickettii in
      an older patient. CASE PRESENTATION: A sixty-five-year old Han Chinese man
      presented having had cough, expectoration, chest pain and fever lasting for
      twenty days. His medical history was notable for hypertension over the previous
      ten years, and the habit of smoking for forty years. A thoracic computed
      tomography scan supported the diagnosis of right-sided lobar pneumonia. A lung
      biopsy was done and pathological analysis confirmed lobar pneumonia. Two lung
      biopsy specimens from separate sites grew Ralstonia pickettii. After six days, a
      repeat thoracic scan revealed a right-sided abscess. A thoracentesis was
      performed and the purulent fluid grew Ralstonia pickettii. The chest tube
      remained inserted to rinse the cavity with sterile sodium chloride. He received
      an antibiotic course of intravenous cefoperazone sodium-sulbactam sodium for
      eighteen days and imipenem-cilastatin for twelve days. A repeat chest X-ray
      revealed resolution of the pulmonary abscess and improvement of pneumonia. He
      remained afebrile and free of respiratory symptoms after treatments. CONCLUSION:
      This case demonstrates a Ralstonia pickettii infection in the absence of an
      obvious nosocomial source. It is possible that such cases will become common in
      the future. Therefore, further studies are needed to evaluate its sensitivity to
      common antibiotics.

PMID- 21843321
TI  - Blunt cerebrovascular trauma causing vertebral arteryd issection in combination
      with a laryngeal fracture: a case report.
AB  - INTRODUCTION: The diagnosis and therapy of blunt cerebrovascular injuries has
      become a focus since improved imaging technology allows adequate description of
      the injury. Although it represents a rare injury the long-term complications can
      be fatal but mostly prevented by adequate treatment. CASE PRESENTATION: A 33-year
      old Caucasian man fell down a 7-meter scarp after losing control of his quad bike
      in a remote area. Since endotracheal intubation was unsuccessfully attempted due
      to the severe cervical swelling as well as oral bleeding an emergency tracheotomy
      was performed on scene. He was hemodynamically unstable despite fluid
      resuscitation and intravenous therapy with vasopressors and was transported by a
      helicopter to our trauma center. He had a stable fracture of the arch of the
      seventh cervical vertebra and fractures of the transverse processes of C5-C7 with
      involvement of the lateral wall of the transverse foramen. An abort of the left
      vertebral artery signal at the first thoracic vertebrae with massive hemorrhage
      as well as a laryngeal fracture was also detected. Further imaging showed
      retrograde filling of the left vertebral artery at C5 distal of the described
      abort. After stabilization and reconfirmation of intracranial perfusion during
      the clinical course weaning was started. At the time of discharge, he was aware
      and was able to move all extremities. CONCLUSION: We report a rare case of a
      patient with vertebral artery dissection in combination with a laryngeal fracture
      after blunt trauma. Thorough diagnostic and frequent reassessments are
      recommended. Most patients can be managed with conservative treatment.

PMID- 21843322
TI  - A modified surgical technique in the management of eyelid burns: a case series.
AB  - INTRODUCTION: Contractures, ectropion and scarring, the most common sequelae of
      skin grafts after eyelid burn injuries, can result in corneal exposure, corneal
      ulceration and even blindness. Split-thickness or full-thickness skin grafts are
      commonly used for the treatment of acute eyelid burns. Plasma exudation and
      infection are common early complications of eyelid burns, which decrease the
      success rate of grafts. CASE PRESENTATION: We present the cases of eight
      patients, two Chinese women and six Chinese men. The first Chinese woman was 36
      years old, with 70% body surface area second or third degree flame burn injuries
      involving her eyelids on both sides. The other Chinese woman was 28 years old,
      with sulfuric acid burns on her face and third degree burn on her eyelids. The
      six Chinese men were aged 21, 31, 38, 42, 44, and 55 years, respectively. The 38
      year-old patient was transferred from the ER with 80% body surface area second or
      third degree flame burn injuries and third degree burn injuries to his eyelids.
      The other five men were all patients with flame burn injuries, with 7% to 10%
      body surface area third degree burns and eyelids involved. All patients were
      treated with a modified surgical procedure consisting of separation and loosening
      of the musculus orbicularis oculi between tarsal plate and septum orbital,
      followed by grafting a large full-thickness skin graft in three days after burn
      injury. The use of our modified surgical procedure resulted in 100% successful
      eyelid grafting on first attempt, and all our patients were in good condition at
      six-month follow-up. CONCLUSIONS: This new surgical technique is highly
      successful in treating eyelid burn injuries, especially flame burn injuries of
      the eyelid.

PMID- 21843323
TI  - Bardet-Biedl syndrome with end-stage kidney disease in a four-year-old Romanian
      boy: a case report.
AB  - BACKGROUND: Bardet-Biedl syndrome is a significant genetic cause of chronic
      kidney disease in children. Kidney abnormalities are a major cause of morbidity
      and mortality in Bardet-Biedl syndrome, but the onset of end-stage renal disease
      at an early age and continuous ambulatory peritoneal dialysis, however, are not
      commonly mentioned in the literature. CASE PRESENTATION: We present the case of a
      four-year-old Romanian boy who presented to our department with 'febrile
      seizures'. After an initial evaluation, we diagnosed our patient as having
      hypertension, severe anemia and end-stage renal disease. He met the major and
      minor criteria for the diagnosis of Bardet-Biedl syndrome and underwent
      continuous ambulatory peritoneal dialysis. CONCLUSIONS: Close follow-up for renal
      involvement in patients with Bardet-Biedl syndrome and Alstrom syndrome from an
      early age is highly recommended to prevent end-stage renal disease and so renal
      replacement therapy can be started immediately.

PMID- 21843324
TI  - Pulmonary histoplasmosis presenting as chronic productive cough, fever, and
      massive unilateral consolidation in a 15-year-old immune-competent boy: a case
      report.
AB  - INTRODUCTION: Severe histoplasmosis is known to be among the AIDS-defining
      opportunistic infections affecting patients with very low CD4 cell counts in
      histoplasmosis-endemic areas. Histoplasma capsulatum var. duboisii is common in
      West and Central Africa, where it occurs in both HIV/AIDS and non-HIV patients.
      Few cases of life-threatening histoplasmosis in immune-competent individuals have
      been reported worldwide. CASE REPORT: We describe a case of pulmonary
      histoplasmosis diagnosed on the basis of autopsy and histological investigations.
      A 15-year old East African immune-competent boy with a history of smear-positive
      tuberculosis and a two-year history of rock cutting presented to our hospital
      with chronic productive cough, fever, and massive unilateral consolidation. At
      the time of presentation to our hospital, this patient was empirically treated
      for recurrent tuberculosis without success, and he died on the seventh day after
      admission. The autopsy revealed a huge granulomatous lesion with caseation, but
      no acid-fast bacilli were detected on several Ziehl-Neelsen stains. However,
      periodic acid-Schiff staining was positive, and the histological examination
      revealed features suggestive of Histoplasma yeast cells. CONCLUSION: Severe
      pulmonary histoplasmosis should be considered in evaluating immune-competent
      patients with risk factors for the disease who present with pulmonary symptoms
      mimicking tuberculosis.

PMID- 21843325
TI  - Cardiovascular events in early RA are a result of inflammatory burden and
      traditional risk factors: a five year prospective study.
AB  - INTRODUCTION: Co-morbidity and mortality due to cardiovascular disease (CVD) are
      increased in patients with rheumatoid arthritis (RA). Most published studies in
      this field are retrospective or cross sectional. We investigated the presence of
      traditional and disease related risk factors for CVD at the onset of RA and
      during the first five years following diagnosis. We also evaluated their
      potential for predicting a new cardiovascular event (CVE) during the five-year
      follow-up period and the modulatory effect of pharmacological treatment. METHODS:
      All patients from the four northern-most counties of Sweden with early RA are,
      since December 1995, consecutively recruited at diagnosis (T0) into a large
      survey on the progress of the disease. Information regarding cardiovascular co
      morbidity and related predictors was collected from clinical records and
      supplemented with questionnaires. By April 2008, 700 patients had been included
      of whom 442 patients had reached the five-year follow-up (T5). RESULTS: Among the
      442 patients who reached T5 during the follow-up period, treatment for
      hypertension increased from 24.5 to 37.4% (P < 0.001)), diagnosis of diabetes
      mellitus (DM) from 7.1 to 9.5% (P < 0.01) whilst smoking decreased from 29.8 to
      22.4% (P < 0.001) and the BMI from 26.3 to 25.8 (P < 0.05), respectively. By T5,
      48 patients had suffered a new CVE of which 12 were fatal. A total of 23 patients
      died during the follow-up period. Age at disease onset, male sex, a previous CVE,
      DM, treatment for hypertension, triglyceride level, cumulative disease activity
      (area under the curve (AUC) disease activity score (DAS28)), extra-articular
      disease, corticosteroid use, shorter duration of treatment with disease modifying
      anti-rheumatic drugs (DMARDs) and use of COX-2 inhibitors increased the hazard
      rate for a new CVE. A raised erythrocyte sedimentation rate (ESR) at inclusion
      and AUC DAS28 at six months increased the hazard rate of CVE independently whilst
      DMARD treatment was protective in multiple Cox extended models adjusted for sex
      and CV risk factors. The risk of a CVE due to inflammation was potentiated by
      traditional CV risk factors. CONCLUSIONS: The occurrence of new CV events in very
      early RA was explained by traditional CV risk factors and was potentiated by high
      disease activity. Treatment with DMARDs decreased the risk. The results may have
      implications for cardio-protective strategies in RA.

PMID- 21843326
TI  - The laval questionnaire: a new instrument to measure quality of life in morbid
      obesity.
AB  - BACKGROUND: Our recent review of the literature uncovered eleven obesity-specific
      quality of life questionnaires, all with incomplete demonstration of their
      measurement properties. Our objective was to validate a new self-administered
      questionnaire specific to morbid obesity to be used in clinical trials. The study
      was carried out at the bariatric surgery clinic of Laval Hospital, Quebec City,
      Canada. METHODS: This study followed our description of health-related quality of
      life in morbid obesity from which we constructed the Laval Questionnaire. Its
      construct validity and responsiveness were tested by comparing the baseline and
      changes at 1-year follow-up in 6 domain scores (symptoms, activity/mobility,
      personal hygiene/clothing, emotions, social interactions, sexual life) with those
      of questionnaires measuring related constructs (SF-36, Impact of Weight on
      Quality of Life-Lite, Rosenberg Self-Esteem Scale and Beck Depression Inventory
      II). RESULTS: 112 patients (67 who got bariatric surgery, 45 who remained on the
      waiting list during the study period) participated in this study. The analysis of
      the discriminative function of the questionnaire showed moderate-to-high
      correlations between the scores in each domain of our instrument and the
      corresponding questionnaires. The analysis of its evaluative function showed (1)
      significant differences in score changes between patients with bariatric surgery
      and those without, and (2) moderate-to-high correlations between the changes in
      scores in the new instrument and the changes in the corresponding questionnaires.
      Most of these correlations met the a priori predictions we had made regarding
      their direction and magnitude. CONCLUSION: The Laval Questionnaire is a valid
      measure of health-related quality of life in patients with morbid obesity and is
      responsive to treatment-induced changes.

PMID- 21843327
TI  - The contrasting roles of PPARdelta and PPARgamma in regulating the metabolic
      switch between oxidation and storage of fats in white adipose tissue.
AB  - BACKGROUND: The nuclear receptors peroxisome proliferator-activated receptor
      gamma (PPARgamma) and peroxisome proliferator-activated receptor delta
      (PPARdelta) play central roles in regulating metabolism in adipose tissue, as
      well as being targets for the treatment of insulin resistance. While the role of
      PPARgamma in regulating insulin sensitivity has been well defined, research into
      PPARdelta has been limited until recently due to a scarcity of selective
      PPARdelta agonists. RESULTS: The metabolic effects of PPARgamma and PPARdelta
      activation have been examined in vivo in white adipose tissue from ob/ob mice and
      in vitro in cultured 3T3-L1 adipocytes using (1)H nuclear magnetic resonance
      spectroscopy and mass spectrometry metabolomics to understand the receptors'
      contrasting roles. These steady state measurements were supplemented with (13)C
      stable isotope substrate labeling to assess fluxes, in addition to respirometry
      and transcriptomic microarray analysis. The metabolic effects of the receptors
      were readily distinguished, with PPARgamma activation characterized by increased
      fat storage, synthesis and elongation, while PPARdelta activation caused
      increased fatty acid beta-oxidation, tricarboxylic acid cycle rate and oxidation
      of extracellular branch chain amino acids. Stimulated glycolysis and increased
      fatty acid desaturation were common pathways for the agonists. CONCLUSIONS:
      PPARgamma and PPARdelta restore insulin sensitivity through varying mechanisms.
      PPARdelta activation increases total oxidative metabolism in white adipose
      tissue, a tissue not traditionally thought of as oxidative. However, the
      increased metabolism of branch chain amino acids may provide a mechanism for
      muscle atrophy, which has been linked to activation of this nuclear receptor.
      PPARdelta has a role as an anti-obesity target and as an anti-diabetic, and hence
      may target both the cause and consequences of dyslipidemia.

PMID- 21843328
TI  - Saleability of anti-malarials in private drug shops in Muheza, Tanzania: a
      baseline study in an era of assumed artemisinin combination therapy (ACT).
AB  - BACKGROUND: Artemether-lumefantrine (ALu) replaced sulphadoxine-pymimethamine
      (SP) as the official first-line anti-malarial in Tanzania in November 2006. So
      far, artemisinin combination therapy (ACT) is contra-indicated during pregnancy
      by the national malaria treatment guidelines, and pregnant women depend on SP for
      Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being
      dispensed by private drug stores, but it is unknown to which extent. If
      significant, it may undermine its official use for IPTp through induction of
      resistance. The main study objective was to perform a baseline study of the
      private market for anti-malarials in Muheza town, an area with widespread anti
      malarial drug resistance, prior to the implementation of a provider training and
      accreditation programme that will allow accredited drug shops to sell subsidized
      ALu. METHODS: All drug shops selling prescription-only anti-malarials, in Muheza
      town, Tanga Region voluntarily participated from July to December 2009.
      Qualitative in-depth interviews were conducted with owners or shopkeepers on
      saleability of anti-malarials, and structured questionnaires provided
      quantitative data on drugs sales volume. RESULTS: All surveyed drug shops
      illicitly sold SP and quinine (QN), and legally amodiaquine (AQ). Calculated
      monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local
      brands of SP accounted for 74% of sales volume, compared to AQ (13%), QN (11%)
      and ACT (2%). CONCLUSIONS: In community practice, the saleability of ACT was
      negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated
      in the national anti-malarial policy. It is a major reason for concern that such
      drug-pressure in the community equals de facto intermittent presumptive
      treatment. In an area where SP drug resistance remains high, unregulated SP
      dispensing to people other than pregnant women runs the risk of eventually
      jeopardizing the effectiveness of the IPTp strategy. Further studies are
      recommended to find out barriers for ACT utilization and preference for self
      medication and to train private drug dispensers.

PMID- 21843329
TI  - Splenic autotransplantation in a patient with human immunodeficiency virus
      infection: a case report.
AB  - INTRODUCTION: Splenectomy is performed mostly because of traumatic events that
      cause rupture of the spleen. Postsplenectomy, a patient has a higher risk of
      developing sepsis. Autotransplantation of splenic tissue decreases the risk of
      opportunistic infection and sepsis, but its role in patients with human
      immunodeficiency virus is debated because the spleen is a replication site,
      especially during the asymptomatic phase of this infection. We present a case of
      a patient with human immunodeficiency virus infection who was admitted to our
      hospital for a traumatic rupture of the spleen and underwent spleen
      autotransplantation. CASE PRESENTATION: A 36-year-old Caucasian man was admitted
      to the shock trauma center of our hospital after a car accident. Anamnesis showed
      that the patient had been human immunodeficiency virus-positive for 13 years. A
      computed tomography scan showed abundant fluid collection in his superior and
      inferior abdomen caused by splenic rupture, with no other associated intra
      abdominal lesions. During surgery, the spleen appeared severely damaged. A
      splenectomy was performed, and 35 g of splenic tissue was autotransplanted in a
      pouch created in the omentum. No complications occurred after surgery, and our
      patient was discharged from our hospital nine days after the operation. One year
      later, computed tomography and scintigraphy showed that the transplanted tissue
      was functioning well. CONCLUSIONS: Autotransplantation of splenic tissue
      decreases the risk of opportunistic infection and sepsis, and it might also be
      useful in patients with human immunodeficiency virus. Other studies need to be
      done to validate this hypothesis.

PMID- 21843330
TI  - Computed tomography colonography imaging of pneumatosis intestinalis after
      hyperbaric oxygen therapy: a case report.
AB  - INTRODUCTION: Pneumatosis intestinalis is a condition characterized by the
      presence of submucosal or subserosal gas cysts in the wall of digestive tract.
      Pneumatosis intestinalis often remains asymptomatic in most cases but may
      clinically present in a benign form or less frequently in fulminant forms.
      Treatment for such conditions includes antibiotic therapy, diet therapy, oxygen
      therapy and surgery. CASE PRESENTATION: The present report describes the case of
      a 56-year-old Swiss-born man with symptomatic pneumatosis intestinalis resistant
      to all treatment except hyperbaric oxygen therapy, as showed by computed
      tomography colonography images performed before, during and after treatment.
      CONCLUSIONS: The current case describes the response to hyperbaric oxygen therapy
      using virtual colonoscopy technique one month and three months after treatment.
      Moreover, after six months of follow-up, there has been no recurrence of
      digestive symptoms.

PMID- 21843331
TI  - Iatrogenic newborn weight loss: knowledge translation using a study protocol for
      your maternity setting.
AB  - BACKGROUND: In our original study of newborn weight loss, we determined there
      were positive correlations among newborn weight loss, neonatal output, and the IV
      fluids mothers received before their babies' birth. Basically, an increase in
      maternal IV fluids is correlated to an increase in neonatal output and newborn
      weight loss. When assessing newborn weight change, our recommendation is to
      change baseline from birth weight to a weight measured at 24 hours. The purpose
      of this paper is to provide a protocol for clinicians to collect and analyze data
      from their own maternity site to determine if the newborns experience such an
      iatrogenic weight loss and to make decisions about how to assess newborn weight
      changes. METHODS: We recommend a prospective observational study with data
      collected about maternal fluids, neonatal output, and newborn weight
      measurements. The methods we suggest include specifics about recruitment, data
      collection, and data analysis. DISCUSSION: Quality assurance and research ethics
      considerations are described. We also share practical information that we learned
      from our original study. Ultimately, to encourage knowledge translation and
      research uptake, we provide a protocol and sound advice to do a research study in
      your maternity setting.

PMID- 21843332
TI  - Increased human defensine levels hint at an inflammatory etiology of
      bisphosphonate-associated osteonecrosis of the jaw: an immunohistological study.
AB  - BACKGROUND: Human beta-defensins (hBD) are antimicrobial peptides that are an
      integral part of bone innate immunity. Recently, it could be shown that
      expression of hBD-1, -2 and -3 were upregulated in cases of osteomyelitis of the
      jaws. In order to gain insight into the possible impairment of hBD metabolism in
      bisphosphonate-associated osteonecrosis of the jaws (BONJ), the present
      exploratory study was designed so as to determine the qualitative and
      quantitative expression of afore mentioned hBDs in BONJ and infected
      osteoradionecrosis (ORN), both of which represent inflammatory bone diseases.
      METHODS: Bone samples were collected from patients with BONJ (n = 20) and ORN (n
      = 20). Non-infected healthy bone samples (n = 20) were included as controls.
      Immunohistological staining in an autostainer was carried out by the (Strept-ABC)
      method against hBD-1,-2,-3. Specific positive vs. negative cell reaction of
      osteocytes (labeling index) near the border of bony resection was determined and
      counted for quantitative analysis. Number of vital osteocytes vs. empty
      osteocytes lacunae was compared between groups. RESULTS: hBD-1,-2 and -3 could be
      detected in BONJ as well as ORN and healthy bone samples. Immunoreactivity
      against hBD-2 and -3 was significantly higher in BONJ than in ORN and healthy jaw
      bone samples. Number of empty osteocyte lacunae was significantly higher in ORN
      compared with BONJ (P = 0.001). CONCLUSION: Under the condition of BONJ an
      increased expression of hBD-1,-2,-3 is detectable, similarly to the recently
      described upregulation of defensins in chronically infected jaw bones. It remains
      still unclear how these findings may relate to the pathoetiology of these
      diseases and whether this is contributing to the development of BONJ and ORN or
      simply an after effect of the disease.

PMID- 21843333
TI  - Global organization of protein complexome in the yeast Saccharomyces cerevisiae.
AB  - BACKGROUND: Proteins in organisms, rather than act alone, usually form protein
      complexes to perform cellular functions. We analyze the topological network
      structure of protein complexes and their component proteins in the budding yeast
      in terms of the bipartite network and its projections, where the complexes and
      proteins are its two distinct components. Compared to conventional protein
      protein interaction networks, the networks from the protein complexes show more
      homogeneous structures than those of the binary protein interactions, implying
      the formation of complexes that cause a relatively more uniform number of
      interaction partners. In addition, we suggest a new optimization method to
      determine the abundance and function of protein complexes, based on the
      information of their global organization. Estimating abundance and biological
      functions is of great importance for many researches, by providing a quantitative
      description of cell behaviors, instead of just a "catalogues" of the lists of
      protein interactions. RESULTS: With our new optimization method, we present
      genome-wide assignments of abundance and biological functions for complexes, as
      well as previously unknown abundance and functions of proteins, which can provide
      significant information for further investigations in proteomics. It is strongly
      supported by a number of biologically relevant examples, such as the relationship
      between the cytoskeleton proteins and signal transduction and the metabolic
      enzyme Eno2's involvement in the cell division process. CONCLUSIONS: We believe
      that our methods and findings are applicable not only to the specific area of
      proteomics, but also to much broader areas of systems biology with the concept of
      optimization principle.

PMID- 21843334
TI  - TP53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma among
      Italian patients.
AB  - BACKGROUND: Single-nucleotide polymorphisms within TP53 gene (codon 72 exon 4,
      rs1042522, encoding either arginine or proline) and MDM2 promoter (SNP309;
      rs2279744), have been independently associated with increased risk of several
      cancer types. Few studies have analysed the role of these polymorphisms in the
      development of hepatocellular carcinoma. METHODS: Genotype distribution of TP53
      codon 72 and MDM2 SNP309 in 61 viral hepatitis-related hepatocellular carcinoma
      cases and 122 blood samples (healthy controls) from Italian subjects were
      determined by PCR and restriction fragment length polymorphism (RFLP). RESULTS:
      Frequencies of TP53 codon 72 alleles were not significantly different between
      cases and controls. A significant increase of MDM2 SNP309 G/G and T/G genotypes
      were observed among hepatocellular carcinoma cases (Odds Ratio, OR = 3.56, 95%
      Confidence Limits, 95% CI = 1.3-9.7; and OR = 2.82, 95% CI = 1.3-6.4,
      respectively). CONCLUSIONS: These results highlight a significant role of MDM2
      SNP309 G allele as a susceptibility gene for the development of viral hepatitis
      related hepatocellular carcinoma among Italian subjects.

PMID- 21843335
TI  - Policy challenges for the pediatric rheumatology workforce: Part II. Health care
      system delivery and workforce supply.
AB  - The United States pediatric population with chronic health conditions is
      expanding. Currently, this demographic comprises 12-18% of the American child and
      youth population. Affected children often receive fragmented, uncoordinated care.
      Overall, the American health care delivery system produces modest outcomes for
      this population. Poor, uninsured and minority children may be at increased risk
      for inferior coordination of services. Further, the United States health care
      delivery system is primarily organized for the diagnosis and treatment of acute
      conditions. For pediatric patients with chronic health conditions, the typical
      acute problem-oriented visit actually serves as a barrier to care. The biomedical
      model of patient education prevails, characterized by unilateral transfer of
      medical information. However, the evidence basis for improvement in disease
      outcomes supports the use of the chronic care model, initially proposed by Dr.
      Edward Wagner. Six inter-related elements distinguish the success of the chronic
      care model, which include self-management support and care coordination by a
      prepared, proactive team. United States health care lacks a coherent policy
      direction for the management of high cost chronic conditions, including rheumatic
      diseases. A fundamental restructure of United States health care delivery must
      urgently occur which places the patient at the center of care. For the pediatric
      rheumatology workforce, reimbursement policies and the actions of health plans
      and insurers are consistent barriers to chronic disease improvement. United
      States reimbursement policy and overall fragmentation of health care services
      pose specific challenges for widespread implementation of the chronic care model.
      Team-based multidisciplinary care, care coordination and self-management are
      integral to improve outcomes. Pediatric rheumatology demand in the United States
      far exceeds available workforce supply. This article reviews the career choice
      decision-making process at each medical trainee level to determine best
      recruitment strategies. Educational debt is an unexpectedly minor determinant for
      pediatric residents and subspecialty fellows. A two-year fellowship training
      option may retain the mandatory scholarship component and attract an increasing
      number of candidate trainees. Diversity, work-life balance, scheduling
      flexibility to accommodate part-time employment, and reform of conditions for
      academic promotion all need to be addressed to ensure future growth of the
      pediatric rheumatology workforce. 

PMID- 21843336
TI  - The influence of a series of five dry cupping treatments on pain and mechanical
      thresholds in patients with chronic non-specific neck pain--a randomised
      controlled pilot study.
AB  - BACKGROUND: In this preliminary trial we investigated the effects of dry cupping,
      an ancient method for treating pain syndromes, on patients with chronic non
      specific neck pain. Sensory mechanical thresholds and the participants' self
      reported outcome measures of pain and quality of life were evaluated. METHODS:
      Fifty patients (50.5 +/- 11.9 years) were randomised to a treatment group (TG) or
      a waiting-list control group (WL). Patients in the TG received a series of 5
      cupping treatments over a period of 2 weeks; the control group did not. Self
      reported outcome measures before and after the cupping series included the
      following: Pain at rest (PR) and maximal pain related to movement (PM) on a 100
      mm visual analogue scale (VAS), pain diary (PD) data on a 0-10 numeric rating
      scale (NRS), Neck Disability Index (NDI), and health-related quality of life (SF
      36). In addition, the mechanical-detection thresholds (MDT), vibration-detection
      thresholds (VDT), and pressure-pain thresholds (PPT) were determined at pain
      related and control areas. RESULTS: Patients of the TG had significantly less
      pain after cupping therapy than patients of the WL group (PR: Delta-22.5 mm, p =
      0.00002; PM: Delta-17.8 mm, p = 0.01). Pain diaries (PD) revealed that neck pain
      decreased gradually in the TG patients and that pain reported by the two groups
      differed significantly after the fifth cupping session (Delta-1.1, p = 0.001).
      There were also significant differences in the SF-36 subscales for bodily pain
      (Delta13.8, p = 0.006) and vitality (Delta10.2, p = 0.006). Group differences in
      PPT were significant at pain-related and control areas (all p < 0.05), but were
      not significant for MDT or VDT. CONCLUSIONS: A series of five dry cupping
      treatments appeared to be effective in relieving chronic non-specific neck pain.
      Not only subjective measures improved, but also mechanical pain sensitivity
      differed significantly between the two groups, suggesting that cupping has an
      influence on functional pain processing. TRIAL REGISTRATION: The trial was
      registered at clinicaltrials.gov (NCT01289964).

PMID- 21843337
TI  - Interventions targeting social isolation in older people: a systematic review.
AB  - BACKGROUND: Targeting social isolation in older people is a growing public health
      concern. The proportion of older people in society has increased in recent
      decades, and it is estimated that approximately 25% of the population will be
      aged 60 or above within the next 20 to 40 years. Social isolation is prevalent
      amongst older people and evidence indicates the detrimental effect that it can
      have on health and wellbeing. The aim of this review was to assess the
      effectiveness of interventions designed to alleviate social isolation and
      loneliness in older people. METHODS: Relevant electronic databases (MEDLINE,
      EMBASE, ASSIA, IBSS, PsycINFO, PubMed, DARE, Social Care Online, the Cochrane
      Library and CINAHL) were systematically searched using an extensive search
      strategy, for randomised controlled trials and quasi-experimental studies
      published in English before May 2009. Additional articles were identified through
      citation tracking. Studies were included if they related to older people, if the
      intervention aimed to alleviate social isolation and loneliness, if intervention
      participants were compared against inactive controls and, if treatment effects
      were reported. Two independent reviewers extracted data using a standardised
      form. Narrative synthesis and vote-counting methods were used to summarise and
      interpret study data. RESULTS: Thirty two studies were included in the review.
      There was evidence of substantial heterogeneity in the interventions delivered
      and the overall quality of included studies indicated a medium to high risk of
      bias. Across the three domains of social, mental and physical health, 79% of
      group-based interventions and 55% of one-to-one interventions reported at least
      one improved participant outcome. Over 80% of participatory interventions
      produced beneficial effects across the same domains, compared with 44% of those
      categorised as non-participatory. Of interventions categorised as having a
      theoretical basis, 87% reported beneficial effects across the three domains
      compared with 59% of interventions with no evident theoretical foundation.
      Regarding intervention type, 86% of those providing activities and 80% of those
      providing support resulted in improved participant outcomes, compared with 60% of
      home visiting and 25% of internet training interventions. Fifty eight percent of
      interventions that explicitly targeted socially isolated or lonely older people
      reported positive outcomes, compared with 80% of studies with no explicit
      targeting. CONCLUSIONS: More, well-conducted studies of the effectiveness of
      social interventions for alleviating social isolation are needed to improve the
      evidence base. However, it appeared that common characteristics of effective
      interventions were those developed within the context of a theoretical basis, and
      those offering social activity and/or support within a group format.
      Interventions in which older people are active participants also appeared more
      likely to be effective. Future interventions incorporating all of these
      characteristics may therefore be more successful in targeting social isolation in
      older people.

PMID- 21843338
TI  - An observational study of associations among maternal fluids during parturition,
      neonatal output, and breastfed newborn weight loss.
AB  - BACKGROUND: Newborn weight measurements are used as a key indicator of
      breastfeeding adequacy. The purpose of this study was to explore non-feeding
      factors that might be related to newborn weight loss. The relationship between
      the intravenous fluids women receive during parturition (the act of giving birth,
      including time in labour or prior to a caesarean section) and their newborn's
      weight loss during the first 72 hours postpartum was the primary interest.
      METHODS: In this observational cohort study, we collected data about maternal
      oral and IV fluids during labour or before a caesarean section. Participants (n =
      109) weighed their newborns every 12 hours for the first three days then daily to
      Day 14, and they weighed neonatal output (voids and stools) for three days.
      RESULTS: At 60 hours (nadir), mean newborn weight loss was 6.57% (SD 2.51; n =
      96, range 1.83-13.06%). When groups, based on maternal fluids, were compared
      (<=1200 mls [n = 21] versus > 1200 [n = 53]), newborns lost 5.51% versus 6.93% (p
      = 0.03), respectively. For the first 24 hours, bivariate analyses show positive
      relationships between a) neonatal output and percentage of newborn weight lost
      (r(96) = 0.493, p < 0.001); and b) maternal IV fluids (final 2 hours) and
      neonatal output (r(42) = 0.383, p = 0.012). At 72 hours, there was a positive
      correlation between grams of weight lost and all maternal fluids (r(75) = 0.309,
      p = 0.007). CONCLUSIONS: Timing and amounts of maternal IV fluids appear
      correlated to neonatal output and newborn weight loss. Neonates appear to
      experience diuresis and correct their fluid status in the first 24 hours. We
      recommend a measurement at 24 hours, instead of birth weight, for baseline when
      assessing weight change. Because practices can differ between maternity settings,
      we further suggest that clinicians should collect and analyze data from dyads in
      their care to determine an optimal baseline measurement.

PMID- 21843339
TI  - Intratracheal transplantation of human umbilical cord blood-derived mesenchymal
      stem cells attenuates Escherichia coli-induced acute lung injury in mice.
AB  - BACKGROUND: Human umbilical cord blood (UCB)-derived mesenchymal stem cells
      (MSCs) attenuate hyperoxic neonatal lung injury primarily through anti
      inflammatory effects. We hypothesized that intratracheal transplantation of human
      UCB-derived MSCs could attenuate Escherichia coli (E. coli)-induced acute lung
      injury (ALI) in mice by suppressing the inflammatory response. METHODS: Eight
      week-old male ICR mice were randomized to control or ALI groups. ALI was induced
      by intratracheal E. coli instillation. Three-hours after E. coli instillation,
      MSCs, fibroblasts or phosphate-buffered saline were intratracheally administered
      randomly and survival was analyzed for 7 days post-injury. Lung histology
      including injury scores, myeloperoxidase (MPO) activity, and protein levels of
      interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and
      macrophage inflammatory protein (MIP)-2 as well as the wet-dry lung ratio and
      bacterial counts from blood and bronchoalveolar lavage (BAL) were evaluated at 1,
      3, and 7 days post-injury. Levels of inflammatory cytokines in the lung were also
      profiled using protein macroarrays at day 3 post-injury which showed peak
      inflammation. RESULTS: MSC transplantation increased survival and attenuated lung
      injuries in ALI mice, as evidenced by decreased injury scores on day 3 post
      injury and reduced lung inflammation including increased MPO activity and protein
      levels of IL-1alpha, IL-1beta, IL-6, TNF-alpha, and MIP-2 on day 3 and 7 post
      injury. Inflammatory cytokine profiles in the lungs at day 3 post-injury were
      attenuated by MSC transplantation. MSCs also reduced the elevated lung water
      content at day 3 post-injury and bacterial counts in blood and BAL on day 7 post
      injury. CONCLUSIONS: Intratracheal transplantation of UCB-derived MSCs attenuates
      E. coli-induced ALI primarily by down-modulating the inflammatory process and
      enhancing bacterial clearance.

PMID- 21843340
TI  - Hand-grip strength is a simple and effective outcome predictor in esophageal
      cancer following esophagectomy with reconstruction: a prospective study.
AB  - BACKGROUND: Surgery for esophageal cancer usually carries considerable
      complication and mortality rate. Adequate preoperative evaluation is mandatory to
      decrease complication rate. Hand-grip strength is a useful measure to assess the
      extent of aging, nutrition and patient's overall condition. Because preoperative
      nutrition state and physiologic aging process play important roles in
      postoperative recovery, we would like to know if hand-grip strength is an
      adequate tool for such evaluation. MATERIAL AND METHODS: From January 1st, 2007
      to December 31, 2008, there was 68 cases underwent esophagectomy with
      reconstruction due to esophageal cancer in our hospital. After excluding 7
      patients of incomplete data and loss of follow-up, there were 61 patients
      included in the study. RESULTS: There were 54 men and 7 women. The mean age is
      60.7. Most of patients had squamous cell carcinoma. Patient with weak hand-grip
      strength prior to operation had exceedingly high rates of complication and
      mortality within 6 months after operation. Compared to other risk factors, low
      grip strength has highest relative risks for both mortality and morbidity.
      CONCLUSION: Because test for hand-grip strength is cheap, not time-consuming and
      has high predictive value, it may be included in routine preoperative evaluation.

PMID- 21843341
TI  - Exploring pathway interactions in insulin resistant mouse liver.
AB  - BACKGROUND: Complex phenotypes such as insulin resistance involve different
      biological pathways that may interact and influence each other. Interpretation of
      related experimental data would be facilitated by identifying relevant pathway
      interactions in the context of the dataset. RESULTS: We developed an analysis
      approach to study interactions between pathways by integrating gene and protein
      interaction networks, biological pathway information and high-throughput data.
      This approach was applied to a transcriptomics dataset to investigate pathway
      interactions in insulin resistant mouse liver in response to a glucose challenge.
      We identified regulated pathway interactions at different time points following
      the glucose challenge and also studied the underlying protein interactions to
      find possible mechanisms and key proteins involved in pathway cross-talk. A large
      number of pathway interactions were found for the comparison between the two diet
      groups at t = 0. The initial response to the glucose challenge (t = 0.6) was
      typed by an acute stress response and pathway interactions showed large overlap
      between the two diet groups, while the pathway interaction networks for the late
      response were more dissimilar. CONCLUSIONS: Studying pathway interactions
      provides a new perspective on the data that complements established pathway
      analysis methods such as enrichment analysis. This study provided new insights in
      how interactions between pathways may be affected by insulin resistance. In
      addition, the analysis approach described here can be generally applied to
      different types of high-throughput data and will therefore be useful for analysis
      of other complex datasets as well.

PMID- 21843342
TI  - Comparison of genomic and proteomic data in recurrent airway obstruction affected
      horses using Ingenuity Pathway Analysis(r).
AB  - BACKGROUND: Recurrent airway obstruction (RAO) is a severe chronic respiratory
      disease affecting horses worldwide, though mostly in the Northern hemisphere.
      Environmental as well as genetic factors strongly influence the course and
      prognosis of the disease. Research has been focused on characterization of
      immunologic factors contributing to inflammatory responses, on genetic linkage
      analysis, and, more recently, on proteomic analysis of airway secretions from
      affected horses. The goal of this study was to investigate the interactions
      between eight candidate genes previously identified in a genetic linkage study
      and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from
      healthy and RAO-affected horses. The analysis was carried out with Ingenuity
      Pathway Analysis(r) bioinformatics software. RESULTS: The gene with the greatest
      number of indirect interactions with the set of proteins identified is
      Interleukin 4 Receptor (IL-4R), whose protein has also been detected in BALF.
      Interleukin 21 receptor and chemokine (C-C motif) ligand 24 also showed a large
      number of interactions with the group of detected proteins. Protein products of
      other genes like that of SOCS5, revealed direct interactions with the IL-4R
      protein. The interacting proteins NOD2, RPS6KA5 and FOXP3 found in several
      pathways are reported regulators of the NFkappaB pathway. CONCLUSIONS: The
      pathways generated with IL-4R highlight possible important intracellular
      signaling cascades implicating, for instance, NFkappaB. Furthermore, the proposed
      interaction between SOCS5 and IL-4R could explain how different genes can lead to
      identical clinical RAO phenotypes, as observed in two Swiss Warmblood half
      sibling families because these proteins interact upstream of an important cascade
      where they may act as a functional unit.

PMID- 21843343
TI  - Strong cardiovascular prognostic implication of quantitative left atrial
      contractile function assessed by cardiac magnetic resonance imaging in patients
      with chronic hypertension.
AB  - BACKGROUND: Progressive left ventricular (LV) diastolic dysfunction due to
      hypertension (HTN) alters left atrial (LA) contractile function in a predictable
      manner. While increased LA size is a marker of LV diastolic dysfunction and has
      been shown to be predictive of adverse cardiovascular outcomes, the prognostic
      significance of altered LA contractile function is unknown. METHODS: A
      consecutive group of patients with chronic hypertension but without significant
      valvular disease or prior MI underwent clinically-indicated CMR for assessment of
      left ventricular (LV) function, myocardial ischemia, or viability. Calculation of
      LA volumes used in determining LA emptying functions was performed using the
      biplane area-length method. RESULTS: Two-hundred and ten patients were included
      in this study. During a median follow-up of 19 months, 48 patients experienced
      major adverse cardiac events (MACE), including 24 deaths. Decreased LA
      contractile function (LAEF(Contractile)) demonstrated strong unadjusted
      associations with patient mortality, non-fatal events, and all MACE. For every
      10% reduction of LAEF(Contractile), unadjusted hazards to MACE, all-cause
      mortality, and non-fatal events increased by 1.8, 1.5, and 1.4-folds,
      respectively. In addition, preservation of the proportional contribution from LA
      contraction to total diastolic filling (Contractile/Total ratio) was strongly
      associated with lower MACE and patient mortality. By multivariable analyses,
      LAEF(Contractile) was the strongest predictor in each of the best overall models
      of MACE, all-cause mortality, and non-fatal events. Even after adjustment for
      age, gender, left atrial volume, and LVEF, LAEF(Contractile) maintained strong
      independent associations with MACE (p < 0.0004), all-cause mortality (p <
      0.0004), and non-fatal events (p < 0.0004). CONCLUSIONS: In hypertensive patients
      at risk for left ventricular diastolic dysfunction, a decreased contribution of
      LA contractile function to ventricular filling during diastole is strongly
      predictive of adverse cardiac events and death.

PMID- 21843344
TI  - Development and evaluation of a web-based breast cancer cultural competency
      course for primary healthcare providers.
AB  - BACKGROUND: To develop and evaluate a continuing medical education (CME) course
      aimed at improving healthcare provider knowledge about breast cancer health
      disparities and the importance of cross-cultural communication in provider
      patient interactions about breast cancer screening. METHODS: An interactive web
      based CME course was developed and contained information about breast cancer
      disparities, the role of culture in healthcare decision making, and demonstrated
      a model of cross-cultural communication. A single group pre-/post-test design was
      used to assess knowledge changes. Data on user satisfaction was also collected.
      RESULTS: In all, 132 participants registered for the CME with 103 completing both
      assessments. Differences between pre-/post-test show a significant increase in
      knowledge (70% vs. 94%; p < .001). Ninety-five percent of participants agreed
      that the web based training was an appropriate tool to train healthcare providers
      about cultural competency and health disparities. CONCLUSION: There was an
      overall high level of satisfaction among all users. Users felt that learning
      objectives were met and the web-based format was appropriate and easy to use and
      suggests that web-based CME formats are an appropriate tool to teach cultural
      competency skills. However, more information is needed to understand how the CME
      impacted practice behaviors.

PMID- 21843345
TI  - Media composition influences yeast one- and two-hybrid results.
AB  - Although yeast two-hybrid experiments are commonly used to identify protein
      interactions, the frequent occurrence of false negatives and false positives
      hampers data interpretation. Using both yeast one-hybrid and two-hybrid
      experiments, we have identified potential sources of these problems: the media
      preparation protocol and the source of the yeast nitrogen base may not only
      impact signal range but also effect whether a result appears positive or
      negative. While altering media preparation may optimize signal differences for
      individual experiments, media preparation must be reported in detail to replicate
      studies and accurately compare results from different experiments.

PMID- 21843346
TI  - Effects of acute adult and early-in-life bladder inflammation on bladder
      neuropeptides in adult female rats.
AB  - BACKGROUND: The purpose of the present study was to determine how acute adult
      and/or prior early-in life (EIL; P14-P16) exposure to bladder inflammation
      affects bladder content of calcitonin gene related peptide (CGRP) and substance P
      (SP). Estrous cycle influences were also studied in the adult-treatment
      conditions. METHODS: In Experiment 1, intravesical zymosan or isoflurane
      anesthesia alone was administered to adult female rats. Bladders and serum were
      collected 24 hours later during each phase of the estrous cycle. In Experiment 2,
      zymosan or anesthesia alone was administered EIL and as adults, with bladder
      tissue collection 24 h later. RESULTS: In general, Experiment 1 showed that
      bladder content of both CGRP and SP was increased by inflammation. This effect
      was significant when data were collapsed across all phases of the estrous cycle,
      but was only significant during proestrus when individual comparisons were made
      during each phase of estrous. Also, adult bladder inflammation significantly
      reduced estradiol levels. In Experiment 2, bladder content of CGRP and SP was
      significantly increased in rats receiving EIL and/or adult inflammation. Bladder
      weights were also significantly increased by inflammation. CONCLUSIONS: These
      data indicate that bladder CGRP and SP are maximally increased during the
      proestrus phase of the estrous cycle in inflamed adult female rats. EIL exposure
      to bladder inflammation alone can also produce an increase in CGRP and SP lasting
      into adulthood. Therefore, EIL experience with bladder inflammation may
      predispose an organism to experience a painful bladder disorder as an adult by
      increasing primary afferent content of CGRP and/or SP.

PMID- 21843347
TI  - Lipopolysaccharide-induced Notch signaling activation through JNK-dependent
      pathway regulates inflammatory response.
AB  - BACKGROUND: Notch and TLR pathways were found to act cooperatively to activate
      Notch target genes and to increase the production of TLR-induced cytokines in
      macrophages. However, the mechanism of LPS-induced Notch activation and its role
      in sepsis still remains unclear. METHODS: We analyzed the expression patterns of
      Notch components in a LPS-stimulated murine macrophage cell line using real-time
      PCR and western blotting. The role of DAPT, a gamma-secretase inhibitor that is
      known to be a potent Notch inhibitor, in LPS-induced cytokine release and
      experimental sepsis in mice was also explored. Student's t-test was used to
      analyze the difference between the two groups. RESULTS: We found that Notch
      signaling was activated after LPS stimulation. The expression of Jagged 1, a
      Notch ligand, induced by LPS occurred in a JNK-dependent manner. In addition,
      Notch target genes were upregulated by early Notch-independent activation
      followed by delayed Notch-dependent activation after LPS stimulation. Disruption
      of Notch signaling by DAPT attenuated the LPS-induced inflammatory responses,
      including vascular endothelial growth factor (VEGF) and high-mobility group box
      chromosomal protein 1 (HMGB1), both in vitro and in vivo and partially improved
      experimental sepsis survival. CONCLUSIONS: These findings support the existence
      of a synergistic effect of Notch signaling and the LPS pathway both in vitro and
      in vivo. Therefore, in the future Notch inhibitors may be utilized as adjunctive
      agents for the treatment of sepsis syndrome.

PMID- 21843348
TI  - Dominance of variant A in human herpesvirus 6 viraemia after renal
      transplantation.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6), mostly variant B reactivation in renal
      transplant patients has been published by other authors, but the pathogenetic
      role of HHV-6 variant A has not been clarified. Our aims were to examine the
      prevalence of HHV-6, to determine the variants, and to investigate the
      interaction between HHV-6 viraemia, human cytomegalovirus (HCMV) infection and
      clinical symptoms. METHODS: Variant-specific HHV-6 nested PCR and quantitative
      real-time PCR were used to examine blood samples from renal transplant patients
      and healthy blood donors for the presence and load of HHV-6 DNA and to determine
      the variants. Active HHV-6 infection was proved by RT-PCR, and active HCMV
      infection was diagnosed by pp65 antigenaemia test. RESULTS: HHV-6 viraemia was
      significantly more frequent in renal transplant patients compared to healthy
      blood donors (9/200 vs. 0/200; p = 0.004), while prevalence of HHV-6 latency was
      not significantly different (13/200 vs. 19/200; p > 0.05). Dominance of variant A
      was revealed in viraemias (8/9), and the frequency of HHV-6A was significantly
      higher in active infections compared with latency in renal transplant patients
      (8/9 vs. 2/13; p = 0.0015). Latency was established predominantly by HHV-6B both
      in renal transplant patients and in healthy blood donors (11/13 and 18/19). There
      was no statistical significant difference in occurrence of HCMV and HHV-6
      viraemia in renal transplant patients (7/200 vs. 9/200). Statistical analysis did
      not reveal interaction between HHV-6 viraemia and clinical symptoms in our study.
      CONCLUSIONS: Contrary to previous publications HHV-6A viraemia was found to be
      predominant in renal transplant patients. Frequency of variant A was
      significantly higher in cases of active infection then in latency.

PMID- 21843349
TI  - The proteasome inhibitor MG132 reduces immobilization-induced skeletal muscle
      atrophy in mice.
AB  - BACKGROUND: Skeletal muscle atrophy is a serious concern for the rehabilitation
      of patients afflicted by prolonged limb restriction. This debilitating condition
      is associated with a marked activation of NFkappaB activity. The ubiquitin
      proteasome pathway degrades the NFkappaB inhibitor IkappaBalpha, enabling
      NFkappaB to translocate to the nucleus and bind to the target genes that promote
      muscle atrophy. Although several studies showed that proteasome inhibitors are
      efficient to reduce atrophy, no studies have demonstrated the ability of these
      inhibitors to preserve muscle function under catabolic condition. METHODS: We
      recently developed a new hindlimb immobilization procedure that induces
      significant skeletal muscle atrophy and used it to show that an inflammatory
      process characterized by the up-regulation of TNFalpha, a known activator of the
      canonical NFkappaB pathway, is associated with the atrophy. Here, we used this
      model to investigate the effect of in vivo proteasome inhibition on the muscle
      integrity by histological approach. TNFalpha, IL-1, IL-6, MuRF-1 and
      Atrogin/MAFbx mRNA level were determined by qPCR. Also, a functional measurement
      of locomotors activity was performed to determine if the treatment can shorten
      the rehabilitation period following immobilization. RESULTS: In the present
      study, we showed that the proteasome inhibitor MG132 significantly inhibited
      IkappaBalpha degradation thus preventing NFkappaB activation in vitro. MG132
      preserved muscle and myofiber cross-sectional area by downregulating the muscle
      specific ubiquitin ligases atrogin-1/MAFbx and MuRF-1 mRNA in vivo. This effect
      resulted in a diminished rehabilitation period. CONCLUSION: These finding
      demonstrate that proteasome inhibitors show potential for the development of
      pharmacological therapies to prevent muscle atrophy and thus favor muscle
      rehabilitation.

PMID- 21843350
TI  - An evaluation of the preoperative hemoglobin level as a prognostic factor for
      oral squamous cell carcinoma.
AB  - BACKGROUND: Hypoxia seems to be an influencing factor for oral squamous cell
      carcinomas (SCC), and several immunohistochemical markers have been discussed in
      this regard. The aim of the present study was to evaluate preoperative hemoglobin
      levels as a prognostic factor for oral SCC. MATERIALS AND METHODS: The files of
      287 patients who had been treated for oral SCC between 1999 and 2008 were studied
      retrospectively. Hemoglobin levels between 1 and 5 days prior to surgical
      treatment were compared to Tumor (T)- and Nodal (N)- status, local recurrence,
      and lymph node metastases rate. The minimum follow-up period was 12 months.
      RESULTS: From a total of 287 patients with oral SCC, 205 (71.4%) were in the
      normal hemoglobin (Hb) group (female Hb >= 12.0 g/dl; male Hb >= 13.0 g/dl), 53
      (18.5%) in the mild anemia (female Hb = 11.0-11.9 g/dl; male Hb = 11.0-12.9
      g/dl), and 29 (10.1%) in the severe anemia group (female & male Hb<11.0 g/dl).
      Anemia was significant for the development of lymph node metastasis (p = 0.005)
      as well as for local recurrence (p = 0.001). No significant correlation was found
      to the initial T status (p = 0.183). CONCLUSION: Our data suggests that an Hb of
      below 11 g/dl contributes to and is an indicator for a poor prognosis.
      Consequently, pre-treatment Hb corrections may significantly improve outcome, but
      further investigations, including blood transfusion/application of erythropoietin
      due to tumor anemia, independent of intraoperative blood-loss are necessary to
      ascertain their role in an improved survival.

PMID- 21843351
TI  - CMV retinitis screening and treatment in a resource-poor setting: three-year
      experience from a primary care HIV/AIDS programme in Myanmar.
AB  - BACKGROUND: Cytomegalovirus retinitis is a neglected disease in resource-poor
      settings, in part because of the perceived complexity of care and because
      ophthalmologists are rarely accessible. In this paper, we describe a pilot
      programme of CMV retinitis management by non-ophthalmologists. The programme
      consists of systematic screening of all high-risk patients (CD4 <100 cells/mm3)
      by AIDS clinicians using indirect ophthalmoscopy, and treatment of all patients
      with active retinitis by intravitreal injection of ganciclovir. Prior to this
      programme, CMV retinitis was not routinely examined for, or treated, in Myanmar.
      METHODS: This is a retrospective descriptive study. Between November 2006 and
      July 2009, 17 primary care AIDS clinicians were trained in indirect
      ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in
      intravitreal injection. Evaluation of training by a variety of methods documented
      high clinical competence. Systematic screening of all high-risk patients (CD4
      <100 cells/mm3) was carried out at five separate AIDS clinics throughout Myanmar.
      RESULTS: A total of 891 new patients (1782 eyes) were screened in the primary
      area (Yangon); the majority of patients were male (64.3%), median age was 32
      years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in
      24% (211/891) of these patients. Bilateral disease was present in 36% of
      patients. Patients with active retinitis were treated with weekly intravitreal
      injection of ganciclovir, with patients typically receiving five to seven
      injections per eye. A total of 1296 injections were administered. CONCLUSIONS: A
      strategy of management of CMV retinitis at the primary care level is feasible in
      resource-poor settings. With appropriate training and support, CMV retinitis can
      be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like
      other major opportunistic infections.

PMID- 21843352
TI  - Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with
      a positive maternal outcome: case report.
AB  - Lassa fever (LF) is a devastating viral disease prevalent in West Africa. Efforts
      to take on this public health crisis have been hindered by lack of infrastructure
      and rapid field deployable diagnosis in areas where the disease is prevalent.
      Recent capacity building at the Kenema Government Hospital Lassa Fever Ward (KGH
      LFW) in Sierra Leone has lead to a major turning point in the diagnosis,
      treatment and study of LF. Herein we present the first comprehensive rapid
      diagnosis and real time characterization of an acute hemorrhagic LF case at KGH
      LFW. This case report focuses on a third trimester pregnant Sierra Leonean woman
      from the historically non-endemic Northern district of Tonkolili who survived the
      illness despite fetal demise. Employed in this study were newly developed
      recombinant LASV Antigen Rapid Test cassettes and dipstick lateral flow
      immunoassays (LFI) that enabled the diagnosis of LF within twenty minutes of
      sample collection. Deregulation of overall homeostasis, significant hepatic and
      renal system involvement, and immunity profiles were extensively characterized
      during the course of hospitalization. Rapid diagnosis, prompt treatment with a
      full course of intravenous (IV) ribavirin, IV fluids management, and real time
      monitoring of clinical parameters resulted in a positive maternal outcome despite
      admission to the LFW seven days post onset of symptoms, fetal demise, and a
      natural still birth delivery. These studies solidify the growing rapid
      diagnostic, treatment, and surveillance capabilities at the KGH LF Laboratory,
      and the potential to significantly improve the current high mortality rate caused
      by LF. As a result of the growing capacity, we were also able to isolate Lassa
      virus (LASV) RNA from the patient and perform Sanger sequencing where we found
      significant genetic divergence from commonly circulating Sierra Leonean strains,
      showing potential for the discovery of a newly emerged LASV strain with expanded
      geographic distribution. Furthermore, recent emergence of LF cases in Northern
      Sierra Leone highlights the need for superior diagnostics to aid in the
      monitoring of LASV strain divergence with potentially increased geographic
      expansion.

PMID- 21843353
TI  - Hemodynamic monitoring and management in patients undergoing high risk surgery: a
      survey among North American and European anesthesiologists.
AB  - INTRODUCTION: Several studies have demonstrated that perioperative hemodynamic
      optimization has the ability to improve postoperative outcome in high-risk
      surgical patients. All of these studies aimed at optimizing cardiac output and/or
      oxygen delivery in the perioperative period. We conducted a survey with the
      American Society of Anesthesiologists (ASA) and the European Society of
      Anaesthesiology (ESA) to assess current hemodynamic management practices in
      patients undergoing high-risk surgery in Europe and in the United States.
      METHODS: A survey including 33 specific questions was emailed to 2,500 randomly
      selected active members of the ASA and to active ESA members. RESULTS: Overall,
      368 questionnaires were completed, 57.1% from ASA and 42.9% from ESA members.
      Cardiac output is monitored by only 34% of ASA and ESA respondents (P = 0.49)
      while central venous pressure is monitored by 73% of ASA respondents and 84% of
      ESA respondents (P < 0.01). Specifically, the pulmonary artery catheter is being
      used much more frequently in the US than in Europe in the setup of high-risk
      surgery (85.1% vs. 55.3% respectively, P < 0.001). Clinical experience, blood
      pressure, central venous pressure, and urine output are the most widely
      indicators of volume expansion. Finally, 86.5% of ASA respondents and 98.1% of
      ESA respondents believe that their current hemodynamic management could be
      improved. CONCLUSIONS: In conclusion, these results point to a considerable gap
      between the accumulating evidence about the benefits of perioperative hemodynamic
      optimization and the available technologies that may facilitate its clinical
      implementation, and clinical practices in both Europe and the United States.

PMID- 21843354
TI  - What do we have to know from migrants' past exposures to understand their health
      status? a life course approach.
AB  - Empirical findings show that morbidity and mortality risks of migrants can
      differ considerably from those of populations in the host countries. However,
      while several explanatory models have been developed, most migrant studies still
      do not consider explicitly the situation of migrants before migration. Here, we
      discuss an extended approach to understand migrant health comprising a life
      course epidemiology perspective.The incorporation of a life course perspective
      into a conceptual framework of migrant health enables the consideration of risk
      factors and disease outcomes over the different life phases of migrants, which is
      necessary to understand the health situation of migrants and their offspring.
      Comparison populations need to be carefully selected depending on the study
      questions under consideration within the life course framework.Migrant health
      research will benefit from an approach using a life course perspective. A
      critique of the theoretical foundations of migrant health research is essential
      for further developing both the theoretical framework of migrant health and
      related empirical studies.

PMID- 21843355
TI  - Calcitonin substitution in calcitonin deficiency reduces particle-induced
      osteolysis.
AB  - BACKGROUND: Periprosthetic osteolysis is a major cause of aseptic loosening in
      joint arthroplasty. This study investigates the impact of CT (calcitonin)
      deficiency and CT substitution under in-vivo circumstances on particle-induced
      osteolysis in Calca -/- mice. METHODS: We used the murine calvarial osteolysis
      model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10
      C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided
      into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles
      (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with
      UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and
      calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle
      implantation and calcitonin substitution (Group 6). Analytes were extracted from
      serum and urine. Bone resorption was measured by bone histomorphometry. The
      number of osteoclasts was determined by counting the tartrate-resistant acid
      phosphatase (TRACP) + cells. RESULTS: Bone resorption was significantly increased
      in Calca -/- mice compared with their corresponding WT. The eroded surface in
      Calca -/- mice with particle implantation was reduced by 20.6% after CT
      substitution. Osteoclast numbers were significantly increased in Calca -/- mice
      after particle implantation. Serum OPG (osteoprotegerin) increased significantly
      after CT substitution. CONCLUSIONS: As anticipated, Calca -/- mice show extensive
      osteolysis compared with wild-type mice, and CT substitution reduces particle
      induced osteolysis.

PMID- 21843356
TI  - Birth outcomes in South African women receiving highly active antiretroviral
      therapy: a retrospective observational study.
AB  - BACKGROUND: Use of highly active antiretroviral therapy (HAART), a triple-drug
      combination, in HIV-infected pregnant women markedly reduces mother to child
      transmission of HIV and decreases maternal morbidity. However, there remains
      uncertainty about the effects of in utero exposure to HAART on foetal
      development. METHODS: Our objectives were to investigate whether in utero
      exposure to HAART is associated with low birth weight and/or preterm birth in a
      population of South African women with advanced HIV disease. A retrospective
      observational study was performed on women with CD4 counts <=250 cells/mm3
      attending antenatal antiretroviral clinics in Johannesburg between October 2004
      and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks)
      were compared between those exposed and unexposed to HAART during pregnancy.
      Effects of different HAART regimen and duration were assessed. RESULTS: Among
      HAART-unexposed infants, 27% (60/224) were low birth weight compared with 23%
      (90/388) of early HAART-exposed (exposed <28 weeks gestation) and 19% (76/407) of
      late HAART-exposed (exposed >=28 weeks) infants (p = 0.05). In the early HAART
      group, a higher CD4 cell count was protective against low birth weight (AOR 0.57
      per 50 cells/mm3 increase, 95% CI 0.45-0.71, p < 0.001) and preterm birth (AOR
      0.68 per 50 cells/mm3 increase, 95% CI 0.55-0.85, p = 0.001). HAART exposure was
      associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%,
      or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and
      efavirenz-based regimens having the strongest associations with preterm birth
      (AOR 5.4, 95% CI 2.1-13.7, p < 0.001, and AOR 5.6, 95% CI 2.1-15.2, p = 0.001,
      respectively). CONCLUSIONS: In this immunocompromised cohort, in utero HAART
      exposure was not associated with low birth weight. An association between NNRTI
      based HAART and preterm birth was detected, but residual confounding is
      plausible. More advanced immunosuppression was a risk factor for low birth weight
      and preterm birth, highlighting the importance of earlier HAART initiation in
      women to optimize maternal health and improve infant outcomes.

PMID- 21843357
TI  - Spontaneous adrenal pheochromocytoma rupture complicated by intraperitoneal
      hemorrhage and shock.
AB  - MEN2A is a hereditary syndrome characterized by medullary thyroid carcinoma,
      hyperparathyroidism, and pheochromocytoma. Classically patients with a
      pheochromocytoma initially present with the triad of paroxysmal headaches,
      palpitations, and diaphoresis accompanied by marked hypertension. However,
      although reported as a rare presentation, spontaneous hemorrhage within a
      pheochromocytoma can present as an abdominal catastrophe. Unrecognized, this
      transformation can rapidly result in death. We report the only documented case of
      a thirty eight year old gentleman with MEN2A who presented to a community
      hospital with hemorrhagic shock and peritonitis secondary to an unrecognized
      hemorrhagic pheochromocytoma. The clinical course is notable for an inability to
      localize the source of hemorrhage during an initial damage control laparotomy
      that stabilized the patient sufficiently to allow emergent transfer to our
      facility, re-exploration for continued hemorrhage and abdominal compartment
      syndrome, and ultimately angiographic embolization of the left adrenal artery for
      control of the bleeding. Following recovery from his critical illness and
      appropriate medical management for pheochromocytoma, he returned for interval
      bilateral adrenal gland resection, from which his recovery was unremarkable. Our
      review of the literature highlights the high mortality associated with the
      undertaking of an operative intervention in the face of an unrecognized
      functional pheochromocytoma. This reinforces the need for maintaining a high
      index of suspicion for pheochromocytoma in similar cases. Our case also
      demonstrates the need for a mutimodal treatment approach that will often be
      required in these cases.

PMID- 21843358
TI  - Quality of life assessment as a predictor of survival in non-small cell lung
      cancer.
AB  - BACKGROUND: There are conflicting and inconsistent results in the literature on
      the prognostic role of quality of life (QoL) in cancer. We investigated whether
      QoL at admission could predict survival in lung cancer patients. METHODS: The
      study population consisted of 1194 non-small cell lung cancer patients treated at
      our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ
      C30 prior to initiation of treatment. Patient survival was defined as the time
      interval between the date of first patient visit and the date of death from any
      cause/date of last contact. Univariate and multivariate Cox regression evaluated
      the prognostic significance of QoL. RESULTS: Mean age at presentation was 58.3
      years. There were 605 newly diagnosed and 589 previously treated patients; 601
      males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III,
      348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as
      well as physical function predicted patient survival in the entire study
      population. Every 10-point increase in physical function was associated with a
      10% increase in survival (95% CI = 6% to 14%, p < 0.001). Similarly, every 10
      point increase in global QoL was associated with a 9% increase in survival (95%
      CI = 6% to 11%, p < 0.001). Furthermore, physical function, nausea/vomiting,
      insomnia, and diarrhea (p < 0.05 for all) in newly diagnosed patients, but only
      physical function (p < 0.001) in previously treated patients were predictive of
      survival. CONCLUSIONS: Baseline global QoL and physical function provide useful
      prognostic information in non-small cell lung cancer patients.

PMID- 21843359
TI  - Gene expression profiling of human whole blood samples with the Illumina WG-DASL
      assay.
AB  - BACKGROUND: Microarray-based gene expression analysis of peripheral whole blood
      is a common strategy in the development of clinically relevant biomarker panels
      for a variety of human diseases. However, the results of such an analysis are
      often plagued by decreased sensitivity and reliability due to the effects of
      relatively high levels of globin mRNA in whole blood. Globin reduction assays
      have been shown to overcome such effects, but they require large amounts of total
      RNA and may induce distinct gene expression profiles. The Illumina whole genome
      DASL assay can detect gene expression levels using partially degraded RNA samples
      and has the potential to detect rare transcripts present in highly heterogeneous
      whole blood samples without the need for globin reduction. We assessed the
      utility of the whole genome DASL assay in an analysis of peripheral whole blood
      gene expression profiles. RESULTS: We find that gene expression detection is
      significantly increased with the use of whole genome DASL compared to the
      standard IVT-based direct hybridization. Additionally, globin-probe negative
      whole genome DASL did not exhibit significant improvements over globin-probe
      positive whole genome DASL. Globin reduction further increases the detection
      sensitivity and reliability of both whole genome DASL and IVT-based direct
      hybridization with little effect on raw intensity correlations. Raw intensity
      correlations between total RNA and globin reduced RNA were 0.955 for IVT-based
      direct hybridization and 0.979 for whole genome DASL. CONCLUSIONS: Overall, the
      detection sensitivity of the whole genome DASL assay is higher than the IVT-based
      direct hybridization assay, with or without globin reduction, and should be
      considered in conjunction with globin reduction methods for future blood-based
      gene expression studies.

PMID- 21843360
TI  - Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of
      the literature and two pediatric cases.
AB  - Severe acute graft versus host disease (GvHD) is a life-threatening complication
      after allogeneic hematopoietic stem cell transplantation. Human mesenchymal
      stromal cells (MSCs) play an important role in endogenous tissue repair and
      possess strong immune-modulatory properties making them a promising tool for the
      treatment of steroid-refractory GvHD. To date, a few reports exist on the use of
      MSCs in treatment of GvHD in children indicating that children tend to respond
      better than adults, albeit with heterogeneous results.We here present a review of
      the literature and the clinical course of two instructive pediatric patients with
      acute steroid-refractory GvHD after haploidentical stem cell transplantation,
      which exemplify the beneficial effects of third-party transplanted MSCs in
      treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis
      of clinical studies addressing the outcome of patients with steroid-refractory
      GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61
      children). Our meta-analysis demonstrates that the overall response-rate is high
      (73.8%) and confirms, for the first time, that children indeed respond better to
      treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%,
      respectively).These data emphasize the significance of this therapeutic approach
      especially in children and indicate that future prospective studies are needed to
      assess the reasons for the observed differential response-rates in pediatric and
      adult patients.

PMID- 21843361
TI  - Axillary lymph node dissection for breast cancer utilizing Harmonic Focus(r).
AB  - BACKGROUND: For patients with axillary lymph node metastases from breast cancer,
      performance of a complete axillary lymph node dissection (ALND) is the standard
      approach. Due to the rich lymphatic network in the axilla, it is necessary to
      carefully dissect and identify all lymphatic channels. Traditionally, these
      lymphatics are sealed with titanium clips or individually sutured. Recently, the
      Harmonic Focus(r), a hand-held ultrasonic dissector, allows lymphatics to be
      sealed without the utilization of clips or ties. We hypothesize that ALND
      performed with the Harmonic Focus(r) will decrease operative time and reduce post
      operative complications. METHODS: Retrospective review identified all patients
      who underwent ALND at a teaching hospital between January of 2005 and December of
      2009. Patient demographics, presenting pathology, treatment course, operative
      time, days to drain removal, and surgical complications were recorded.
      Comparisons were made to a selected control group of patients who underwent
      similar surgical procedures along with an ALND performed utilizing hemostatic
      clips and electrocautery. A total of 41 patients were included in this study.
      RESULTS: Operative time was not improved with the use of ultrasonic dissection,
      however, there was a decrease in the total number of days that closed suction
      drainage was required, although this was not statistically significant.
      Complication rates were similar between the two groups. CONCLUSION: In this case
      matched retrospective review, there were fewer required days of closed suction
      drainage when ALND was performed with ultrasonic dissection versus clips and
      electrocautery.

PMID- 21843362
TI  - Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS)
      treated with anthracycline-containing chemotherapy.
AB  - BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a
      heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes.
      The aim of this study was to evaluate whether lymphopenia at diagnosis would have
      an adverse effect on survival in patients with PTCL-NOS treated with
      anthracycline-containing chemotherapy. METHODS: A total of 118 patients with PTCL
      NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions
      were included. RESULTS: Thirty-six patients (30.5%) had a low absolute lymphocyte
      count (ALC, < 1.0 * 109/L) at diagnosis. Patients with lymphopenia had shorter
      overall survival (OS) and progression-free survival (PFS) rates compared with
      patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate
      analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores
      and lymphopenia were both associated with shorter OS and PFS. Treatment-related
      mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P =
      0.003). In patients considered high-intermediate/high-risk based on IPI scores,
      lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001,
      respectively). CONCLUSION: This study suggests that lymphopenia could be an
      independent prognostic marker to predict unfavorable OS and PFS in patients with
      PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to
      further stratify high-risk patients using IPI scores.

PMID- 21843363
TI  - The predictability of serum anti-Mullerian level in IVF/ICSI outcomes for
      patients of advanced reproductive age.
AB  - BACKGROUND: The role of serum anti-Mullerian hormone (AMH) as predictor of in
      vitro fertilization outcomes has been much debated. The aim of the present study
      is to investigate the practicability of combining serum AMH level with biological
      age as a simple screening method for counseling IVF candidates of advanced
      reproductive age with potential poor outcomes prior to treatment initiation.
      METHODS: A total of 1,538 reference patients and 116 infertile patients aged
      greater than or equal to 40 years enrolled in IVF/ICSI cycles were recruited in
      this retrospective analysis. A reference chart of the age-related distribution of
      serum AMH level for Asian population was first created. IVF/ICSI patients aged
      greater than or equal to 40 years were then divided into three groups according
      to the low, middle and high tertiles the serum AMH tertiles derived from the
      reference population of matching age. The cycle outcomes were analyzed and
      compared among each individual group. RESULTS: For reference subjects aged
      greater than or equal to 40 years, the serum AMH of the low, middle and high
      tertiles were equal or lesser than 0.48, 0.49-1.22 and equal or greater than 1.23
      ng/mL respectively. IVF/ICSI patients aged greater than or equal to 40 years with
      AMH levels in the low tertile had the highest cycle cancellation rate (47.6%)
      with zero clinical pregnancy. The nadir AMH level that has achieved live birth
      was 0.56 ng/mL, which was equivalent to the 36.4th percentile of AMH level from
      the age-matched reference group. The optimum cut-off levels of AMH for the
      prediction of nonpregnancy and cycle cancellation were 1.05 and 0.68 ng/mL,
      respectively. CONCLUSIONS: Two criteria: (1) age greater than or equal to 40
      years and (2) serum AMH level in the lowest tertile (equal or lesser than 33.3rd
      percentile) of the matching age group, may be used as markers of futility for
      counseling IVF/ICSI candidates.

PMID- 21843364
TI  - Genetic variants of Anaplasma phagocytophilum from 14 equine granulocytic
      anaplasmosis cases.
AB  - BACKGROUND: Equine Granulocytic Anaplasmosis (EGA) is caused by Anaplasma
      phagocytophilum, a tick-transmitted, obligate intracellular bacterium. In Europe,
      it is transmitted by Ixodes ricinus. A large number of genetic variants of A.
      phagocytophilum circulate in nature and have been found in ticks and different
      animals. Attempts have been made to assign certain genetic variants to certain
      host species or pathologies, but have not been successful so far. The purpose of
      this study was to investigate the causing agent A. phagocytophilum of 14 cases of
      EGA in naturally infected horses with molecular methods on the basis of 4 partial
      genes (16S rRNA, groEL, msp2, and msp4). RESULTS: All DNA extracts of EDTA-blood
      samples of the horses gave bands of the correct nucleotide size in all four
      genotyping PCRs. Sequence analysis revealed 4 different variants in the partial
      16S rRNA, groEL gene and msp2 genes, and 3 in the msp4 gene. One 16S rRNA gene
      variant involved in 11 of the 14 cases was identical to the "prototype" variant
      causing disease in humans in the amplified part [GenBank: U02521]. Phylogenetic
      analysis revealed as expected for the groEL gene that sequences from horses
      clustered separately from roe deer. Sequences of the partial msp2 gene from this
      study formed a separate cluster from ruminant variants in Europe and from all US
      variants. CONCLUSIONS: The results show that more than one variant of A.
      phagocytophilum seems to be involved in EGA in Germany. The comparative genetic
      analysis of the variants involved points towards different natural cycles in the
      epidemiology of A. phagocytophilum, possibly involving different reservoir hosts
      or host adaptation, rather than a strict species separation.

PMID- 21843365
TI  - Yolk sac tumor in a patient with transverse testicular ectopia.
AB  - Transverse testicular ectopia (TTE) is a rare anomaly in which both testes
      descend through a single inguinal canal. We report a case of yolk sac tumor in
      the ectopic testis of a patient with TTE. A 24-year-old man presented to our
      hospital with a left inguinal-mass, right cryptorchidism and elevated alpha
      fetoprotein (AFP). A left herniotomy 3 years earlier demonstrated both testes in
      the left scrotum, one above another positionally. Four months ago, a left scrotal
      mass appeared and radical orchiectomy of both testes revealed testicular yolk sac
      tumor of the ectopic testis. An enlarging left inguinal-mass appeared 2 months
      ago and he was referred to our hospital. Laboratory data showed an elevation of
      AFP (245.5 ng/ml) and a 46 XY karyotype. He underwent bilateral retroperitoneal
      lymph node dissection and simultaneous left inguinal mass dissection.
      Histopathologic examination revealed a diagnosis of recurrent yolk sac tumor in
      the left inguinal mass. The retroperitoneal lymph node was not enlarged and, on
      histopathology, was not involved. The patient has now been followed up for 8
      months without evidence of biochemical or radiological recurrence.

PMID- 21843366
TI  - The protocol of a randomized controlled trial for playgroup mothers: Reminder on
      Food, Relaxation, Exercise, and Support for Health (REFRESH) Program.
AB  - BACKGROUND: Mother's physical activity levels are relatively low, while their
      energy consumption is generally high resulting in 58% of Australian women over
      the age of 18 years being overweight or obese. This study aims to confirm if a
      low-cost, accessible playgroup based intervention program can improve the dietary
      and physical activity behaviours of mothers with young children. METHODS/DESIGN:
      The current study is a randomized controlled trial lifestyle (nutrition and
      physical activity) intervention for mothers with children aged between 0 to 5
      years attending playgroups in Perth, Western Australia. Nine-hundred participants
      will be recruited and randomly assigned to the intervention (n = 450) and control
      (n = 450) groups. The study is based on the Social Cognitive Theory (SCT) and the
      Transtheoretical Model (TTM), and the Precede-Proceed Framework incorporating
      goal setting, motivational interviewing, social support and self-efficacy. The
      six month intervention will include multiple strategies and resources to ensure
      the engagement and retention of participants. The main strategy is home based and
      will include a specially designed booklet with dietary and physical activity
      information, a muscle strength and flexibility exercise chart, a nutrition label
      reading shopping list and menu planner. The home based strategy will be supported
      by face-to-face dietary and physical activity workshops in the playgroup setting,
      posted and emailed bi-monthly newsletters, and monthly Short Message Service
      (SMS) reminders via mobile phones. Participants in the control group receive no
      intervention materials. Outcome measures will be assessed using data that will be
      collected at baseline, six months and 12 months from participants in the control
      and intervention groups. DISCUSSION: This trial will add to the evidence base on
      the recruitment, retention and the impact of community based dietary and physical
      activity interventions for mothers with young children. TRIAL REGISTRATION:
      Australian and New Zealand Clinical Trials Registry ACTRN12609000735257.

PMID- 21843367
TI  - Using scenario tree modelling for targeted herd sampling to substantiate freedom
      from disease.
AB  - BACKGROUND: In order to optimise the cost-effectiveness of active surveillance to
      substantiate freedom from disease, a new approach using targeted sampling of
      farms was developed and applied on the example of infectious bovine
      rhinotracheitis (IBR) and enzootic bovine leucosis (EBL) in Switzerland. Relevant
      risk factors (RF) for the introduction of IBR and EBL into Swiss cattle farms
      were identified and their relative risks defined based on literature review and
      expert opinions. A quantitative model based on the scenario tree method was
      subsequently used to calculate the required sample size of a targeted sampling
      approach (TS) for a given sensitivity. We compared the sample size with that of a
      stratified random sample (sRS) with regard to efficiency. RESULTS: The required
      sample sizes to substantiate disease freedom were 1,241 farms for IBR and 1,750
      farms for EBL to detect 0.2% herd prevalence with 99% sensitivity. Using
      conventional sRS, the required sample sizes were 2,259 farms for IBR and 2,243
      for EBL. Considering the additional administrative expenses required for the
      planning of TS, the risk-based approach was still more cost-effective than a sRS
      (40% reduction on the full survey costs for IBR and 8% for EBL) due to the
      considerable reduction in sample size. CONCLUSIONS: As the model depends on RF
      selected through literature review and was parameterised with values estimated by
      experts, it is subject to some degree of uncertainty. Nevertheless, this approach
      provides the veterinary authorities with a promising tool for future cost
      effective sampling designs.

PMID- 21843368
TI  - Dorsal stream involvement in recognition of objects with transient onset but not
      with ramped onset.
AB  - BACKGROUND: Although the ventral visual stream is understood to be responsible
      for object recognition, it has been proposed that the dorsal stream may
      contribute to object recognition by rapidly activating parietal attention
      mechanisms, prior to ventral stream object processing. METHODS: To investigate
      the relative contribution of the dorsal visual stream to object recognition a
      group of tertiary students were divided into good and poor motion coherence
      groups and assessed on tasks classically assumed to rely on ventral stream
      processing. Participants were required to identify simple line drawings in two
      tasks, one where objects were presented abruptly for 50 ms followed by a white
      noise mask, the other where contrast was linearly ramped on and off over 325 ms
      and replaced with a mask. RESULTS: Although both groups only differed in motion
      coherence performance (a dorsal stream measure), the good motion coherence group
      showed superior contrast sensitivity for object recognition on the abrupt, but
      not the ramped presentation tasks. CONCLUSIONS: We propose that abrupt
      presentation of objects activated attention mechanisms fed by the dorsal stream,
      whereas the ramped presentation had reduced transience and thus did not activate
      dorsal attention mechanisms as well. The results suggest that rapid dorsal stream
      activation may be required to assist with ventral stream object processing.

PMID- 21843369
TI  - Possible association between interleukin-1beta gene and schizophrenia in a
      Japanese population.
AB  - BACKGROUND: Several lines of evidence have implicated the pro-inflammatory
      cytokine interleukin-1beta (IL-1beta) in the etiology of schizophrenia. Although
      a number of genetic association studies have been reported, very few have
      systematically examined gene-wide tagging polymorphisms. METHODS: A total of 533
      patients with schizophrenia (302 males: mean age +/- standard deviation 43.4 +/-
      13.0 years; 233 females; mean age 44.8 +/- 15.3 years) and 1136 healthy controls
      (388 males: mean age 44.6 +/- 17.3 years; 748 females; 46.3 +/- 15.6 years) were
      recruited for this study. All subjects were biologically unrelated Japanese
      individuals. Five tagging polymorphisms of IL-1beta gene (rs2853550, rs1143634,
      rs1143633, rs1143630, rs16944) were examined for association with schizophrenia.
      RESULTS: Significant difference in allele distribution was found between patients
      with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was
      performed separately in each gender, significant difference between patients and
      controls in allele distribution of rs1143633 was observed in females (P =
      0.0073). A trend towards association was also found between rs16944 and female
      patients with schizophrenia (P = 0.032). CONCLUSIONS: The present study shows the
      first evidence that the IL-1beta gene polymorphism rs1143633 is associated with
      schizophrenia susceptibility in a Japanese population. The results suggest the
      possibility that the influence of IL-1beta gene variations on susceptibility to
      schizophrenia may be greater in females than in males. Findings of the present
      study provide further support for the role of IL-1beta in the etiology of
      schizophrenia.

PMID- 21843370
TI  - Peripheral anti-inflammatory effects explain the ginsenosides paradox between
      poor brain distribution and anti-depression efficacy.
AB  - BACKGROUND: The effectiveness of ginseng in preventing and treating various
      central nervous system (CNS) diseases has been widely confirmed. However,
      ginsenosides, the principal components of ginseng, are characterized by poor
      accessibility to the brain, and this pharmacokinetic-pharmacological paradox
      remains poorly explained. Anti-inflammatory approaches are becoming promising
      therapeutic strategies for depression and other CNS diseases; however, previous
      studies have focused largely on anti-inflammatory therapies directed at the
      central nervous system. It is thus of interest to determine whether ginsenosides,
      characterized by poor brain distribution, are also effective in treating
      lipopolysaccharide- (LPS) induced depression-like behavior and neuroinflammation.
      METHODS: In an LPS-induced depression-like behavior model, the antidepressant
      effects of ginseng total saponins (GTS) were assessed using a forced swimming
      test, a tail suspension test, and a sucrose preference test. The anti
      inflammatory efficacies of GTS in brain, plasma, and LPS-challenged RAW264.7
      cells were validated using ELISA and quantitative real-time PCR. Moreover,
      indoleamine 2,3-dioxygenase (IDO) activity in the periphery and brain were also
      determined by measuring levels of kynurenine/tryptophan. RESULTS: GTS
      significantly attenuated LPS-induced depression-like behavior. Moreover, LPS
      induced increases in 5-HT and tryptophane turnover in the brain were
      significantly reduced by GTS. IDO activities in brain and periphery were also
      suppressed after pretreatment with GTS. Furthermore, GTS-associated recovery from
      LPS-induced depression-like behavior was paralleled with reduced mRNA levels for
      IL-1beta, IL-6, TNF-alpha, and IDO in hippocampus. Poor brain distribution of
      ginsenosides was confirmed in LPS-challenged mice. GTS treatment significantly
      decreased production of various proinflammatory cytokines in both LPS-challenged
      mice and RAW264.7 cells. CONCLUSION: This study suggests that the anti-depression
      efficacy of GTS may be largely attributable to its peripheral anti-inflammatory
      activity. Our study also strengthens an important notion that peripheral anti
      inflammation strategies may be useful in the therapy of inflammation-related
      depression and possibly other CNS diseases.

PMID- 21843371
TI  - The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to
      gemcitabine-induced apoptosis by suppressing NF-kappaB activity and down
      regulating Bfl-1.
AB  - Gemcitabine is used to treat several cancers including lung cancer. However,
      tumor cells often escape gemcitabine-induced cell death via various mechanisms,
      which include modulating bcl-2 family members and NF-kappaB activation. We
      previously reported that the C-terminal region of Bfl-1 fused with GFP (BC) is
      sufficient to induce apoptosis in 293T cells. In the present study, we
      investigated the anti-tumor effect of combined BC gene therapy and gemcitabine
      chemotherapy in vitro and in vivo using non-small cell lung cancer cell lines and
      a xenograft model. Cell lines were resistant to low dose gemcitabine (4-40
      ng/ml), which induced NF-kappaB activation and concomitant up-regulation of Bfl-1
      (an NF-kappaB-regulated anti-apoptotic protein). BC induced the apoptosis of A549
      and H157 cells with caspase-3 activation. Furthermore, co-treatment with BC and
      low dose gemcitabine synergistically and efficiently induced mitochondria
      mediated apoptosis in these cells. When administered alone or with low dose
      gemcitabine, BC suppressed NF-kappaB activity, inhibited the nuclear
      translocation of p65/relA, and down-regulated Bfl-1 expression. Furthermore,
      direct suppression of Bfl-1 by RNA interference sensitized cells to gemcitabine
      induced cell death, suggesting that Bfl-1 importantly regulates lung cancer cell
      sensitivity to gemcitabine. BC and gemcitabine co-treatment also showed a strong
      anti-tumor effect in a nude mouse/A549 xenograft model. These results suggest
      that lung cancer cells become resistant to gemcitabine via NF-kappaB activation
      and the subsequent overexpression of Bfl-1, and that BC, which has both pro
      apoptotic and NF-kappaB inhibitory effects, could be harnessed as a gene therapy
      to complement gemcitabine chemotherapy in non-small cell lung cancer.

PMID- 21843372
TI  - Expression of urease by Haemophilus influenzae during human respiratory tract
      infection and role in survival in an acid environment.
AB  - BACKGROUND: Nontypeable Haemophilus influenzae is a common cause of otitis media
      in children and lower respiratory tract infection in adults with chronic
      obstructive pulmonary disease (COPD). Prior studies have shown that H. influenzae
      expresses abundant urease during growth in the middle ear of the chinchilla and
      in pooled human sputum, suggesting that expression of urease is important for
      colonization and infection in the hostile environments of the middle ear and in
      the airways in adults. Virtually nothing else is known about the urease of H.
      influenzae, which was characterized in the present study. RESULTS: Analysis by
      reverse transcriptase PCR revealed that the ure gene cluster is expressed as a
      single transcript. Knockout mutants of a urease structural gene (ureC) and of the
      entire ure operon demonstrated no detectable urease activity indicating that this
      operon is the only one encoding an active urease. The ure operon is present in
      all strains tested, including clinical isolates from otitis media and COPD.
      Urease activity decreased as nitrogen availability increased. To test the
      hypothesis that urease is expressed during human infection, purified recombinant
      urease C was used in ELISA with pre acquisition and post infection serum from
      adults with COPD who experienced infections caused by H. influenzae. A total of
      28% of patients developed new antibodies following infection indicating that H.
      influenzae expresses urease during airway infection. Bacterial viability assays
      performed at varying pH indicate that urease mediates survival of H. influenzae
      in an acid environment. CONCLUSIONS: The H. influenzae genome contains a single
      urease operon that mediates urease expression and that is present in all clinical
      isolates tested. Nitrogen availability is a determinant of urease expression. H.
      influenzae expresses urease during human respiratory tract infection and urease
      is a target of the human antibody response. Expression of urease enhances
      viability in an acid environment. Taken together, these observations suggest that
      urease is important for survival and replication of H. influenzae in the human
      respiratory tract.

PMID- 21843373
TI  - Overexpression of Insig-1 protects beta cell against glucolipotoxicity via SREBP
      1c.
AB  - BACKGROUND: High glucose induced lipid synthesis leads to beta cell
      glucolipotoxicity. Sterol regulatory element binding protein-1c (SREBP-1c) is
      reported to be partially involved in this process. Insulin induced gene-1 (Insig
      1) is an important upstream regulator of Insig-1-SREBPs cleavage activating
      protein (SCAP)-SREBP-1c pathway. Insig-1 effectively blocks the transcription of
      SREBP-1c, preventing the activation of the genes for lipid biosynthesis. In this
      study, we aimed to investigate whether Insig-1 protects beta cells against
      glucolipotoxicity. METHODS: An Insig-1 stable cell line was generated by
      overexpression of Insig-1 in INS-1 cells. The expression of Insig-1 was evaluated
      by RT-PCR and Western blotting, then, cells were then treated with standard (11.2
      mM) or high (25.0 mM) glucose for 0 h, 24 h and 72 h. Cell viability, apoptosis,
      glucose stimulated insulin secretion (GSIS), lipid metabolism and mRNA expression
      of insulin secretion relevant genes such as IRS-2, PDX-1, GLUT-2, Insulin and UCP
      2 were evaluated. RESULTS: We found that Insig-1 suppressed the high glucose
      induced SREBP-1c mRNA and protein expression. Our results also showed that Insig
      1 overexpression protected beta cells from ER stress-induced apoptosis by
      regulating the proteins expressed in the IRE1alpha pathway, such as p-IRE1alpha,
      p-JNK, CHOP and BCL-2. In addition, Insig-1 up-regulated the expression of IRS-2,
      PDX-1, GLUT-2 and Insulin, down-regulated the expression of UCP-2 and improved
      glucose stimulated insulin secretion (GSIS). Finally, we found that Insig-1
      inhibited the lipid accumulation and free fatty acid (FFA) synthesis in a time
      dependent manner. CONCLUSIONS: There results suggest that Insig-1 may play a
      critical role in protecting beta cells against glucolipotoxicity by regulating
      the expression of SREBP-1c.

PMID- 21843374
TI  - Synthetic long oligonucleotides to generate artificial templates for use as
      positive controls in molecular assays: drug resistance mutations in influenza
      virus as an example.
AB  - BACKGROUND: Positive controls are an integral component of any sensitive
      molecular diagnostic tool, but this can be affected, if several mutations are
      being screened in a scenario of a pandemic or newly emerging disease where it can
      be difficult to acquire all the necessary positive controls from the host. This
      work describes the development of a synthetic oligo-cassette for positive
      controls for accurate and highly sensitive diagnosis of several mutations
      relevant to influenza virus drug resistance. RESULTS: Using influenza antiviral
      drug resistance mutations as an example by employing the utility of synthetic
      paired long oligonucleotides containing complementary sequences at their 3' ends
      and utilizing the formation of oligonucleotide dimers and DNA polymerization, we
      generated ~170bp dsDNA containing several known specific neuraminidase inhibitor
      (NAI) resistance mutations. These templates were further cloned and successfully
      applied as positive controls in downstream assays. CONCLUSION: This approach
      significantly improved the development of diagnosis of resistance mutations in
      terms of time, accuracy, efficiency and sensitivity, which are paramount to
      monitoring the emergence and spread of antiviral drug resistant influenza
      strains. Thus, this may have a significantly broader application in molecular
      diagnostics along with its application in rapid molecular testing of all relevant
      mutations in an event of pandemic.

PMID- 21843375
TI  - Cellular prion protein protects from inflammatory and neuropathic pain.
AB  - Cellular prion protein (PrPC) inhibits N-Methyl-D-Aspartate (NMDA) receptors.
      Since NMDA receptors play an important role in the transmission of pain signals
      in the dorsal horn of spinal cord, we thus wanted to determine if PrPC null mice
      show a reduced threshold for various pain behaviours.We compared nociceptive
      thresholds between wild type and PrPC null mice in models of inflammatory and
      neuropathic pain, in the presence and the absence of a NMDA receptor antagonist.
      2-3 months old male PrPC null mice exhibited an MK-801 sensitive decrease in the
      paw withdrawal threshold in response both mechanical and thermal stimuli. PrPC
      null mice also exhibited significantly longer licking/biting time during both the
      first and second phases of formalin-induced inflammation of the paw, which was
      again prevented by treatment of the mice with MK-801, and responded more strongly
      to glutamate injection into the paw. Compared to wild type animals, PrPC null
      mice also exhibited a significantly greater nociceptive response (licking/biting)
      after intrathecal injection of NMDA. Sciatic nerve ligation resulted in MK-801
      sensitive neuropathic pain in wild-type mice, but did not further augment the
      basal increase in pain behaviour observed in the null mice, suggesting that mice
      lacking PrPC may already be in a state of tonic central sensitization.
      Altogether, our data indicate that PrPC exerts a critical role in modulating
      nociceptive transmission at the spinal cord level, and fit with the concept of
      NMDA receptor hyperfunction in the absence of PrPC.

PMID- 21843376
TI  - Protocol--realist and meta-narrative evidence synthesis: evolving standards
      (RAMESES).
AB  - BACKGROUND: There is growing interest in theory-driven, qualitative and mixed
      method approaches to systematic review as an alternative to (or to extend and
      supplement) conventional Cochrane-style reviews. These approaches offer the
      potential to expand the knowledge base in policy-relevant areas - for example by
      explaining the success, failure or mixed fortunes of complex interventions.
      However, the quality of such reviews can be difficult to assess. This study aims
      to produce methodological guidance, publication standards and training resources
      for those seeking to use the realist and/or meta-narrative approach to systematic
      review. METHODS/DESIGN: We will: [a] collate and summarise existing literature on
      the principles of good practice in realist and meta-narrative systematic review;
      [b] consider the extent to which these principles have been followed by published
      and in-progress reviews, thereby identifying how rigour may be lost and how
      existing methods could be improved; [c] using an online Delphi method with an
      interdisciplinary panel of experts from academia and policy, produce a draft set
      of methodological steps and publication standards; [d] produce training materials
      with learning outcomes linked to these steps; [e] pilot these standards and
      training materials prospectively on real reviews-in-progress, capturing
      methodological and other challenges as they arise; [f] synthesise expert input,
      evidence review and real-time problem analysis into more definitive guidance and
      standards; [g] disseminate outputs to audiences in academia and policy. The
      outputs of the study will be threefold:1. Quality standards and methodological
      guidance for realist and meta-narrative reviews for use by researchers, research
      sponsors, students and supervisors2. A 'RAMESES' (Realist and Meta-review
      Evidence Synthesis: Evolving Standards) statement (comparable to CONSORT or
      PRISMA) of publication standards for such reviews, published in an open-access
      academic journal.3. A training module for researchers, including learning
      outcomes, outline course materials and assessment criteria. DISCUSSION: Realist
      and meta-narrative review are relatively new approaches to systematic review
      whose overall place in the secondary research toolkit is not yet fully
      established. As with all secondary research methods, guidance on quality
      assurance and uniform reporting is an important step towards improving quality
      and consistency of studies.

PMID- 21843377
TI  - Clinical use of neuroimaging in dementia: an international perspective.

PMID- 21843378
TI  - Dopaminergic imaging: clinical utility now and in the future.
AB  - Over the past ten years, dopaminergic imaging has become increasingly part of the
      assessment and diagnosis of dementia. There are numerous PET and SPECT ligands
      available that target different steps in the process of neurotransmission.
      Abnormalities in dopaminergic imaging measures are consistent features of
      dementia with Lewy bodies (DLB) and other parkinsonian syndromes, and can be used
      to facilitate diagnosis, particularly in distinguishing between DLB and
      Alzheimer's disease. This review summarizes present knowledge in this area and
      the implications for current and future clinical practice.

PMID- 21843379
TI  - Other magnetic resonance imaging techniques.
AB  - Relatively new developments in MRI, such as functional MRI (fMRI), magnetic
      resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) are rapidly
      developing into imaging modalities that will become clinically available in the
      near future. They have in common that their signal is somewhat easier to
      interpret than structural MRI: fMRI mirrors excess cerebral blood flow, in many
      cases representing brain activity, MRS gives the average volume concentrations of
      specific chemical compounds, and DTI reflects "directedness" of micro-anatomical
      structures, of particular use in white matter where fiber bundle disruption can
      be detected with great sensitivity. While structural changes in MRI have been
      disappointing in giving a diagnosis of sufficient sensitivity and specificity,
      these newer methods hold out hope for elucidating pathological changes and
      differentiating patient groups more rigorously. This paper summarizes promising
      research results that will yet have to be translated into real life clinical
      studies in larger groups of patients (e.g. memory clinic patients). Where
      available, we have tried to summarize results comparing different types of
      dementia.

PMID- 21843380
TI  - An international perspective on advanced neuroimaging: cometh the hour or ivory
      tower?
AB  - Over the past five to ten years, neuroimaging capability for neurodegenerative
      diseases has made remarkable progress. However, debate remains as to the true
      clinical utility of these advanced and costly investigations. Not only is the
      place of these tests in diagnostic algorithms unclear, but the access to them
      varies both within and between countries. We sought to gather informed opinion
      from recognized leaders in the field who can combine both an academic and a
      clinical perspective on the use of neuroimaging in their own countries. Opinion
      is presented from Scotland, Argentina, the Czech Republic, France, the USA and
      Australia. The emerging consensus was one of ongoing caution. While in most
      countries there was a sense that the use of more advanced imaging techniques was
      growing, their hour has not yet cometh. However, these techniques, rather than
      falling from the Ivory Tower, should descend slowly step by step onto fertile and
      receptive clinics from where better clinical guidelines will emerge.

PMID- 21843381
TI  - Guest Editorial: A call for contextualized bioethics: health, biomedical
      research, and security.

PMID- 21843382
TI  - Informed consent: its history, meaning, and present challenges.

PMID- 21843383
TI  - Limits of autonomy in biomedical ethics?: conceptual clarifications.

PMID- 21843384
TI  - Changing ethical frameworks: from individual rights to the common good?

PMID- 21843385
TI  - The communitarian turn: myth or reality?

PMID- 21843386
TI  - The concepts of common good and public interest: from Plato to biobanking.

PMID- 21843387
TI  - Database research: public and private interests.

PMID- 21843388
TI  - Ethical endgames: broad consent for narrow interests; open consent for closed
      minds.

PMID- 21843389
TI  - Tackling epistemological naivety: large-scale information systems and the
      complexities of the common good.

PMID- 21843390
TI  - A social justice framework for health and science policy.

PMID- 21843391
TI  - Health ideologies, objectivism, and the common good: on the rights of dissidents.

PMID- 21843392
TI  - Subjective Well-Being In Later Life: 20 years after the Butterworths monograph
      series on individual and population aging.
AB  - This article discusses developments in theory and research on happiness two
      decades after publication of Psychological Well-Being in Later Life
      (Butterworths, 1991) by Albert Kozma, Michael Stones, and Kevin McNeil. Major
      empirical advances include new knowledge about contributions to happiness
      resulting from genetically related effects and personality. Personality traits
      have stronger relationships with happiness than was apparent 20 years ago and
      contribute to covariance between happiness and some of its predictors. Evolving
      emphases in research include the ways in which genetically related effects
      influence how people shape, and react to, their environment.

PMID- 21843393
TI  - Hormone variations in serum and milk of buffaloes (Bubalus bubalis) as potential
      indicators of treatment with recombinant bovine somatotropin.
AB  - Recombinant bovine somatotropin (rbST) is used to increase milk yield in cows,
      but it has been forbidden in some countries and in the EU. However, rbST misuse
      represents a concern in both bovine and buffalo dairy production. A number of
      studies on rbST treatment have been performed on bovines, but there are few data
      on buffaloes. In this study, we treated eight lactating buffaloes with biweekly
      injections of a slow-release formulation of rbST, for five cycles of
      administration, and analysed total ST and insulin-like growth factor 1 (IGF-1)
      variations in serum and IGF-1 in milk. The aim was to assess their power as
      potential indicators of rbST-treatment. Blood was collected on days 2, 5, 9 and
      14 of each cycle, and milk on days 2, 9 and 14 of cycles 2 and 5. Results showed
      an extraordinary increase in ST levels on day 2 in treated animals, followed by a
      rapid decrease over the following days, while a significant increase in IGF-1 was
      observed both in serum and in milk throughout most of each cycle. These results
      suggest that serum ST levels are a good indicator of treatment. However, the
      rapid decrease after the peak limits the useful period of sample collection.

PMID- 21843394
TI  - Milk fatty acid profile related to energy balance in dairy cows.
AB  - Milk fatty acid (FA) profile is a dynamic pattern influenced by lactational
      stage, energy balance and dietary composition. In the first part of this study,
      effects of the energy balance during the proceeding lactation [weeks 1-21 post
      partum (pp)] on milk FA profile of 30 dairy cows were evaluated under a constant
      feeding regimen. In the second part, effects of a negative energy balance (NEB)
      induced by feed restriction on milk FA profile were studied in 40 multiparous
      dairy cows (20 feed-restricted and 20 control). Feed restriction (energy balance
      of -63 MJ NEL/d, restriction of 49 % of energy requirements) lasted 3 weeks
      starting at around 100 days in milk. Milk FA profile changed markedly from week 1
      pp up to week 12 pp and remained unchanged thereafter. The proportion of
      saturated FA (predominantly 10:0, 12:0, 14:0 and 16:0) increased from week 1 pp
      up to week 12 pp, whereas monounsaturated FA, predominantly the proportion of
      18:1,9c decreased as NEB in early lactation became less severe. During the
      induced NEB, milk FA profile showed a similarly directed pattern as during the
      NEB in early lactation, although changes were less marked for most FA. Milk FA
      composition changed rapidly within one week after initiation of feed restriction
      and tended to adjust to the initial composition despite maintenance of a high
      NEB. C18:1,9c was increased significantly during the induced NEB indicating
      mobilization of a considerable amount of adipose tissue. Besides 18:1,9c, changes
      in saturated FA, monounsaturated FA, de-novo synthesized and preformed FA (sum of
      FA >C16) reflected energy status in dairy cows and indicated the NEB in early
      lactation as well as the induced NEB by feed restriction.

PMID- 21843395
TI  - Pattern of serum protein fractions in dairy cows during different stages of
      gestation and lactation.
AB  - In dairy cows the period of transition from late gestation to early lactation is
      recognized as inducing considerable metabolic adaptation. The aim of this study
      was to analyse modifications in serum protein values occurring during the dry and
      the transition period and during lactation in a group of five Holstein cows of
      high average milk production. For all subjects, selected on the basis of their
      pregnancy status, blood samples were collected at different physiological phases:
      dry period (-60, -30 d to calving), transition period (almost 7 d to calving, 7 d
      after calving), and lactation (weeks 2, 5 and 15 after calving), for a total of
      eight blood samples for each cow. On each blood sample total proteins and
      electrophoresis analysis were performed. On the data obtained, normally
      distributed (P<0.05, Kolmogorov-Smirnov's test), one-way Repeated Measure
      Analysis of Variance (ANOVA), was applied to evaluate the influence of different
      stages of gestation and lactation on the considered parameters. Results showed a
      significant effect on total proteins, alpha1-globulins, beta-globulins, gamma
      globulins and albumin/globulin ratio. Most of the detected modifications were
      related to the transition from gestation to lactation, indicating that it is a
      period of great metabolic stress for cows. On the basis of the obtained results
      we can affirm that the pattern of serum protein fraction rn could give
      information about dehydration, plasma volume expansion and hepatic function
      occurring during the peripartum period in dairy cows.

PMID- 21843396
TI  - Ovarian activity in Fleckvieh, Brown Swiss and two strains of Holstein-Friesian
      cows in pasture-based, seasonal calving dairy systems.
AB  - The objectives of the study were to compare the ovarian activity of Holstein
      Friesian (CH HF), Fleckvieh (CH FV) and Brown Swiss (CH BS) dairy cows of Swiss
      origin with that of Holstein-Friesian (NZ HF) dairy cows of New Zealand origin,
      the latter being used as a reference for reproductive performance in pasture
      based seasonal calving systems. Fifty, second-lactation NZ HF cows were each
      paired with a second-lactation Swiss cow (17, 15 and 18 CH HF, CH FV and CH BS
      respectively) in 13 pasture-based, seasonal-calving commercial dairy farms in
      Switzerland. Ovarian activity was monitored by progesterone profiling from
      calving to first breeding service. CH BS cows produced less energy-corrected milk
      (mean 22.8 kg/d) than the other breeds (26.0-26.5 kg/d) during the first 100 d of
      lactation. CH HF cows had the lowest body condition score (BCS) at calving and
      the greatest BCS loss from calving to 30 d post partum. Commencement of luteal
      activity (CLA) was later for NZ HF than for CH FV (51.5 v. 29.2 d; P <0.01), with
      CH HF and CH BS intermediate (43 d). On average, NZ HF and CH HF cows had one
      oestrous cycle before the onset of the seasonal breeding period; this was less
      (P<0.01) than either CH FV (1.7) or CH BS (1.6). There was a low prevalence of
      luteal persistency (3%) among the studied cows. First and second oestrous cycle
      inter-ovulatory intervals did not differ between breeds (20.5-22.6 d). The luteal
      phase length of CH BS during the second cycle was shorter (10.6 d) than that of
      the other breeds (13.8-16.0 d), but the inter-luteal interval was longer (9.8 d
      v. 7.0-8.0 d). The results suggest that the Swiss breeds investigated have a
      shorter interval from calving to CLA than NZ HF cows.

PMID- 21843397
TI  - Effects of season, milking routine and cow cleanliness on bacterial and somatic
      cell counts of bulk tank milk.
AB  - The aim of the study was to investigate the effects of season, cow cleanliness
      and milking routine on bacterial and somatic cell counts of bulk tank milk. A
      total of 22 dairy farms in Lombardy (Italy) were visited three times in a year in
      different seasons. During each visit, samples of bulk tank milk were taken for
      bacterial and somatic cell counts; swabs from the teat surface of a group of cows
      were collected after teat cleaning and before milking. Cow cleanliness was
      assessed by scoring udder, flanks and legs of all milking cows using a 4-point
      scale system. Season affected cow cleanliness with a significantly higher
      percentage of non-clean (NC) cows during Cold compared with Mild season. Standard
      plate count (SPC), laboratory pasteurization count (LPC), coliform count (CC) and
      somatic cell count, expressed as linear score (LS), in milk significantly
      increased in Hot compared with Cold season. Coagulase-positive staphylococci on
      teat swabs showed higher counts in Cold season in comparison with the other ones.
      The effect of cow cleanliness was significant for SPC, psychrotrophic bacterial
      count (PBC), CC and Escherichia coli in bulk tank milk. Somatic cell count showed
      a relationship with udder hygiene score. Milking operation routine strongly
      affected bacterial counts and LS of bulk tank milk: farms that accomplished a
      comprehensive milking scheme including two or more operations among
      forestripping, pre-dipping and post-dipping had lower teat contamination and
      lower milk SPC, PBC, LPC, CC and LS than farms that did not carry out any
      operation.

PMID- 21843398
TI  - Microscopic differential cell counts in milk for the evaluation of inflammatory
      reactions in clinically healthy and subclinically infected bovine mammary glands.
AB  - Somatic cell count (SCC) is generally regarded as an indicator of udder health. A
      cut-off value of 100*10(3) cells/ml is currently used in Germany to differentiate
      between normal and abnormal secretion of quarters. In addition to SCC,
      differential cell counts (DCC) can be applied for a more detailed analysis of the
      udder health status. The aim of this study was to differentiate somatic cells in
      foremilk samples of udder quarters classified as normal secreting by SCC
      <100*10(3) cells/ml. Twenty cows were selected and 72 normal secreting udder
      quarters were compared with a control group of six diseased quarters (SCC
      >100*10(3) cells/ml). In two severely diseased quarters of the control group (SCC
      of 967*10(3) cells/ml and 1824*10(3) cells/ml) Escherichia coli and
      Staphylococcus aureus were detected. DCC patterns of milk samples (n = 25) with
      very low SCC values of <=6.25*10(3)cells/ml revealed high lymphocyte proportions
      of up to 92%. Milk cell populations in samples (n = 41) with SCC values of (>6.25
      to <=25)*10(3) cells/ml were also dominated by lymphocytes (mean value 47%),
      whereas DCC patterns of milk from udder quarters (n = 6) with SCC values (>25 to
      <=100)*10(3)cells/ml changed. While in samples (n = 3) with SCC values of (27
      33)*10(3) cells/ml macrophages were predominant (35-40%), three milk samples with
      (43-45)*10(3) cells/ml indicated already inflammatory reactions based on the
      predominance of polymorphonuclear leucocytes (PMN) (54-63%). In milk samples of
      diseased quarters PMN were categorically found as dominant cell population with
      proportions of >=65%. Macrophages were the second predominant cell population in
      almost all samples tested in relationship to lymphocytes and PMN. To our
      knowledge, this is the first study evaluating cell populations in low SCC milk in
      detail. Udder quarters classified as normal secreting by SCC <100*10(3) cells/ml
      revealed already inflammatory processes based on DCC.

PMID- 21843399
TI  - Validation of the revised Addenbrooke's Cognitive Examination (ACE-R) for
      detecting mild cognitive impairment and dementia in a Japanese population.
AB  - BACKGROUND: Early detection of dementia will be important for implementation of
      disease-modifying treatments in the near future. We aimed to investigate the
      diagnostic validity and reliability of the Japanese version of the revised
      Addenbrooke's Cognitive Examination (ACE-R J) for identifying mild cognitive
      impairment (MCI) and dementia. METHODS: We translated and adapted the original
      ACE-R for use with a Japanese population. Standard tests for evaluating cognitive
      decline and dementing disorders were applied. A total of 242 subjects (controls =
      73, MCI = 39, dementia = 130) participated in this study. RESULTS: The optimal
      cut-off scores of ACE-R J for detecting MCI and dementia were 88/89 (sensitivity
      0.87, specificity 0.92) and 82/83 (sensitivity 0.99, specificity 0.99)
      respectively. ACE-R J was superior to the Mini-Mental State Examination in the
      detection of MCI (area under the curve (AUC): 0.952 vs. 0.868), while the
      accuracy of the two instruments did not differ significantly in identifying
      dementia (AUC: 0.999 vs. 0.993). The inter-rater reliability (ICC = 0.999), test
      retest reliability (ICC = 0.883), and internal consistency (Cronbach's alpha =
      0.903) of ACE-R J were excellent. CONCLUSION: ACE-R J proved to be an accurate
      cognitive instrument for detecting MCI and mild dementia. Further
      neuropsychological evaluation is required for the differential diagnosis of
      dementia subtypes.

PMID- 21843400
TI  - Sedative use and incident cognitive decline among persons aged 75 years and
      older: a population-based longitudinal study.
AB  - BACKGROUND: Acute exposure to sedative drugs may induce memory impairment, but
      there is mixed evidence that long-term sedative use may result in incident
      cognitive decline. The objective of this study was to investigate the use of
      sedative drugs and incident cognitive decline in a population-based sample of
      persons aged 75 years and older. METHODS: The study sample comprised 781
      participants in the Geriatric Multidisciplinary Strategy for the Good Care of the
      Elderly (GeMS) study in Kuopio, Finland. Data on health status, drug use, and
      sociodemographic factors were elicited during annual nurse interviews from 2004
      to 2007. A linear mixed model was used to compare change in Mini-Mental State
      Examination (MMSE) scores (2005-2007) among users of sedative drugs in 2004 and
      2005 (n = 139) to non-users of sedative drugs from 2004 to 2007 (n = 310). The
      model was adjusted for covariates including age, gender, education, depressive
      symptoms and antipsychotic use. RESULTS: Unadjusted mean MMSE scores were 27.50
      in 2005, 26.58 in 2006, and 25.95 in 2007 among users of sedative drugs.
      Unadjusted mean MMSE scores were 28.05 in 2005, 27.61 in 2006, and 27.09 in 2007
      among non-users of sedative drugs. Adjusted mean MMSE scores were 0.31 points
      lower in 2005, 0.62 points lower in 2006, and 0.93 lower in 2007 among users
      compared to non-users of sedative drugs (P = 0.051). CONCLUSIONS: Sedatives were
      not associated with statistically significant cognitive decline. However,
      clinicians should maintain a judicious approach to prescribing sedative drugs
      given the risk of adverse drug events.

PMID- 21843401
TI  - Daily hassles, physical illness, and sleep problems in older adults with wishes
      to die.
AB  - BACKGROUND: Factors associated with the wish to die should be investigated in
      order to gain more opportunities for preventive interventions targeting older
      adults at risk for suicide. The goal of the research was to study the prevalence
      and associated factors of wishes to die in older adults living in the community
      using the data from a survey on the prevalence of mental disorders in this
      population. METHODS: With a representative sample of community living older
      adults aged 65 years and over (N = 2777), we compared individuals with the wish
      to die (n = 163) to those without the wish to die on the basis of the presence
      and severity of daily hassles, physical illness, and sleep quality. RESULTS:
      Logistic regression revealed that when depression and sociodemographic variables
      were held constant, self-rated physical health, number of chronic illnesses,
      number and intensity of daily hassles, as well as sleep problems were
      significantly associated with the wish to die in older adults. Painful illnesses
      and daytime dysfunction due to sleep problems were also associated factors with
      the wish to die. CONCLUSION: Since desire for death is the first step into the
      suicidal process, health professionals should seriously consider the important
      and unique contribution of these variables in order to have more opportunities
      for detection and intervention.

PMID- 21843402
TI  - Rasch analysis of the International Wellbeing Index in older adults.
AB  - BACKGROUND: The International Wellbeing Index is a measure of general quality of
      life formed by two scales: the Personal Wellbeing Index (PWI) and the National
      Wellbeing Index (NWI). This paper studies the psychometric properties of the PWI
      and NWI, using Rasch analysis and classic psychometric methods. METHODS: The PWI
      and NWI were applied to a representative sample of 1106 community-dwelling
      adults, aged 60 years and over, residing in Spain. Mean +/- standard deviation
      age was 72.07 +/- 7.83 years and 56.3% were women. RESULTS: Five PWI items
      (achieving in life, relationships, safety, community connectedness, and future
      security), and five NWI items (economic situation, state of environment, social
      conditions, business, and national security of the country) fitted the Rasch
      model. After adjusting the response scale format, satisfactory fit was obtained,
      with good reliability (person separation index of 0.91 for both the PSI and NWI),
      local independency of items, and strict unidimensionality. The measures showed
      adequate external construct validity with related measures. CONCLUSIONS: The PWI
      and the NWI, with fewer items and simpler response scale formats, provided valid
      and reliable linear measures in older adults, according to Rasch and classic
      psychometric analyses.

PMID- 21843403
TI  - Public policy versus individual rights and responsibility: an economist's
      perspective.
AB  - Interventions to reduce childhood obesity entail ethical considerations. Although
      a rationale exists for government to intervene in a way that limits individual
      rights while protecting the public's health, a clear economic rationale also
      exists. The markets for goods and services that contribute to obesity are
      characterized by multiple failures that create an economic rationale for
      government to intervene (eg, consumers' lack of accurate information regarding
      obesogenic foods and beverages). If effective public policies for reducing
      obesity and its consequences are to be developed and implemented, individual
      rights and government interests must be balanced.

PMID- 21843404
TI  - State requirements and recommendations for school-based screenings for body mass
      index or body composition, 2010.
AB  - INTRODUCTION: We present a comprehensive picture of state requirements and
      recommendations for body mass index (BMI) and body composition screening of
      children and explore the association between pediatric obesity prevalence and
      state screening policies. METHODS: Researchers completed telephone interviews
      with contacts at the departments of education for all 50 states and reviewed
      state content standards for physical education. RESULTS: Twenty states (40%)
      require BMI or body composition screening, and 9 states (18%) recommend BMI
      screening or a formal fitness assessment that includes a body composition
      component. The prevalence of adolescent obesity was higher in states that require
      BMI screening or fitness assessments with body composition than in states without
      requirements (16.7% vs 13.6%, P = .001). CONCLUSION: Future studies should
      evaluate the effect and cost-effectiveness of BMI and body composition screening
      on child obesity.

PMID- 21843405
TI  - A common denominator: calculating hospitalization rates for ambulatory care
      sensitive conditions in California.
AB  - INTRODUCTION: Chronic health conditions are considered ambulatory care-sensitive
      conditions (ACSC) when the illness is controllable with effective and timely
      outpatient care that can potentially prevent the need for hospitalizations.
      Hospitalization rates for ACSC serve as an indicator of the access to and quality
      of primary care for chronic conditions. Standard methods to calculate
      hospitalization rates incorporate the total population in the denominator instead
      of the total population at risk for a hospitalization. By accounting for people
      with an ACSC, this study compares standard methods to a disease prevalence
      adjusted method to highlight the importance of adjusting for ACSC prevalence when
      using ACSC hospitalizations in assessing primary care outpatient services.
      METHODS: We combined California Health Interview Survey and hospital discharge
      data to calculate standard (crude and age-adjusted) and disease prevalence
      adjusted hospitalization rates for hypertension and congestive heart failure. To
      compare rate calculations, we ranked California counties by their hospitalization
      rate. RESULTS: Counties had high prevalence and low numbers of hospitalizations
      for hypertension; their rankings for hospitalization rates for hypertension did
      not vary, even after accounting for prevalence. In contrast, counties had low
      prevalence and high numbers of hospitalizations for congestive heart failure;
      their rankings varied substantially for congestive heart failure after accounting
      for prevalence. CONCLUSION: Because the number of people diagnosed with an ACSC
      is rising and costs to treat these conditions are increasing, our findings
      suggest that more accurate measures of ACSC hospitalization rates are needed.
      Incorporating disease prevalence will contribute to ACSC research by improving
      the validity of hospitalization rates as a measure for quality of primary care
      services.

PMID- 21843406
TI  - PCD's first annual student research contest: Lui and Wallace examine
      hospitalization rates for at-risk populations.

PMID- 21843407
TI  - Vigorous physical activity among tweens, VERB Summer Scorecard program,
      Lexington, Kentucky, 2004-2007.
AB  - INTRODUCTION: Empirical examinations of the efficacy of community-based programs
      to increase and sustain physical activity among youth are lacking. This study
      describes changes in vigorous physical activity during a 3-year period among
      children aged 9 to 13 years (tweens) in Lexington, Kentucky, following
      introduction of the VERB Summer Scorecard (VSS) intervention. METHODS: A
      community coalition, guided by a marketing plan that addressed motivators for
      tweens to participate in physical activity, designed and implemented VSS. Youth
      used a scorecard to monitor their physical activity, which was verified by
      adults. There were 3,428 students surveyed in 2004; 1,976 in 2006; and 2,051 in
      2007 (mean age for 2004, 2006, and 2007, 12 y). For each year, we performed
      Chi(2) tests and computed summary statistics for age, sex, and grade. Chi-square
      tests and cumulative logit models were used to analyze physical activity trends
      among VSS participants, VSS nonparticipants, and a reference group. RESULTS: The
      proportion of youth who reported frequent vigorous physical activity increased
      from 32% in 2004 to 42% in 2007. The proportion of VSS participants with moderate
      or high levels of vigorous physical activity increased by approximately 17
      percentage points, more than twice the proportion of nonparticipants. CONCLUSION:
      Interventions such as VSS may empower communities to take action to encourage
      greater physical activity among youth.

PMID- 21843408
TI  - Associations of American Indian children's screen-time behavior with parental
      television behavior, parental perceptions of children's screen time, and media
      related resources in the home.
AB  - INTRODUCTION: American Indian children have high rates of overweight and obesity,
      which may be partially attributable to screen-time behavior. Young children's
      screen-time behavior is strongly influenced by their environment and their
      parents' behavior. We explored whether parental television watching time,
      parental perceptions of children's screen time, and media-related resources in
      the home are related to screen time (ie, television, DVD/video, video game, and
      computer use) among Oglala Lakota youth residing on or near the Pine Ridge
      Reservation in South Dakota. METHODS: We collected baseline data from 431 child
      and parent/caregiver pairs who participated in Bright Start, a group-randomized,
      controlled, school-based obesity prevention trial to reduce excess weight gain.
      Controlling for demographic characteristics, we used linear regression analysis
      to assess associations between children's screen time and parental television
      watching time, parental perceptions of children's screen time, and availability
      of media-related household resources. RESULTS: The most parsimonious model for
      explaining child screen time included the children's sex, parental body mass
      index, parental television watching time, how often the child watched television
      after school or in the evening, parental perception that the child spent too much
      time playing video games, how often the parent limited the child's television
      time, and the presence of a VCR/DVD player or video game player in the home
      (F(7,367) = 14.67; P < .001; adjusted R(2) = .37). The presence of a television
      in the bedroom did not contribute significantly to the model. CONCLUSION: Changes
      in parental television watching time, parental influence over children's screen
      time behavior, and availability of media-related resources in the home could
      decrease screen time and may be used as a strategy for reducing overweight and
      obesity in American Indian children.

PMID- 21843409
TI  - Parental exposure to carcinogens and risk for childhood acute lymphoblastic
      leukemia, Colombia, 2000-2005.
AB  - INTRODUCTION: The objective of this study was to determine the risk factors for
      childhood acute lymphoblastic leukemia (ALL) and, in particular, the role of
      parental occupational exposure to carcinogenic and probably carcinogenic
      hydrocarbons before the child's conception. METHODS: For this case-control study,
      cases were children younger than 15 years who were newly diagnosed with ALL
      between January 2000 and March 2005 at 1 of 6 Colombian hospitals. An interview
      with both parents of 170 children (85 cases and 85 individually matched
      neighborhood controls) gathered information about each child's exposures and
      parental demographic and occupational characteristics, medical history, health
      risk behaviors, and pregnancy and birth history. A job-exposure matrix was used
      to classify parental exposure to hydrocarbons on the basis of the main industrial
      activity of each workplace where parents worked before (both parents) or during
      the index pregnancy (mother only). Conditional odds ratios and 95% confidence
      intervals were calculated by period of exposure (preconception, pregnancy, and
      childhood). RESULTS: The risk of childhood ALL was linked to 1) parental
      occupational exposure to hydrocarbons before conception, 2) parental smoking
      before conception, 3) maternal low socioeconomic status during pregnancy, and 4)
      higher maternal age (>=35 y) at the child's birth. CONCLUSION: These findings
      suggest an association between childhood ALL and parental occupational exposure
      to carcinogenic and probably carcinogenic hydrocarbons before conception.
      Outcomes depended on the parent exposed. Future research should investigate the
      additive or multiplicative role of other environmental sources of hydrocarbons.

PMID- 21843410
TI  - An observational study of physical activity in parks in Asian and Pacific
      Islander communities in urban Honolulu, Hawaii, 2009.
AB  - INTRODUCTION: Research on park use among Asians and Pacific Islanders is limited.
      This study examined use and conditions of 6 urban parks, varying in size,
      location, and neighborhood income level, in predominantly Asian and Pacific
      Islander communities in Honolulu, Hawaii. Sociodemographic predictors of park use
      were also identified. METHODS: Observations were conducted from June through
      October 2009. Raters used the System for Observing Play and Recreation in
      Communities to count the number of people in predesignated zones and to code
      their physical activity level as sedentary, moderate, or vigorous. Raters coded
      park conditions on the basis of accessibility and usability, whether equipment
      and supervision were provided, and whether organized activities were occurring.
      Differences associated with sex and age of park users and income level of the
      neighborhood were examined by using chi2 and logistic regression. RESULTS: Raters
      observed 6,477 park users, most of whom were men. Approximately 60% of users were
      sedentary, 26% were engaged in moderate activities, and 14% performed vigorous
      activities. Women and girls were less active than men and boys. More users were
      present in the evenings, but morning users were more active. Although park users
      in low-income neighborhoods were more active than users in high-income
      neighborhoods, fewer people used the low-income parks. Most parks were accessible
      and usable but few provided equipment and supervision. Organized activities were
      rarely observed. CONCLUSION: More efforts should be made to promote parks as a
      physical activity resource in Asian and Pacific Islander communities,
      particularly for women, girls, and low-income residents. More research should be
      conducted to identify barriers and facilitators to park use, especially among
      underrepresented populations.

PMID- 21843411
TI  - Regional and racial differences in smoking and exposure to secondhand smoke: the
      Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
AB  - INTRODUCTION: Stroke mortality rates differ by race and region, and smoking and
      exposure to secondhand smoke are associated with stroke. We evaluated regional
      and racial differences in current smoking and secondhand smoke exposure among
      participants in the Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) study. METHODS: African American and white adults (n = 26,373) aged 45
      years or older were recruited during 2003 through 2007. Logistic regression was
      used to examine the likelihood of current smoking and secondhand smoke exposure
      by race (African American vs white) and region. We compared the buckle of the
      stroke belt (the coastal plain region of North Carolina, South Carolina, and
      Georgia) with the stroke belt (the remainder of North Carolina, South Carolina,
      and Georgia, plus Alabama, Mississippi, Tennessee, Arkansas, and Louisiana) and
      compared each of these regions with the remaining contiguous states. RESULTS:
      Among whites, no regional differences in current smoking were seen, but among
      African Americans, the odds of current smoking were 5% lower in the stroke belt,
      and 24% lower in the stroke buckle than those in the nonbelt region. Similarly,
      among whites no regional differences in exposure to secondhand smoke were found,
      whereas among African Americans, the odds of being exposed to secondhand smoke
      were 14% lower in the stroke buckle than for nonbelt residents. CONCLUSION: These
      data suggest that rates of current smoking and secondhand smoke exposure are not
      higher in regions that have higher stroke mortality and therefore cannot
      contribute to geographic disparities; nevertheless, given that 15% of our
      participants reported current smoking and 16% reported secondhand smoke exposure,
      continued implementation of tobacco control policies is needed.

PMID- 21843412
TI  - Awareness, treatment, and control of hypertension and hypercholesterolemia among
      insured residents of New York City, 2004.
AB  - INTRODUCTION: Health care access and sociodemographic characteristics may
      influence chronic disease management even among adults who have health insurance.
      The objective of this study was to examine awareness, treatment, and control of
      hypertension and hypercholesterolemia, by health care access and sociodemographic
      characteristics, among insured adults in New York City. METHODS: Using data from
      the 2004 New York City Health and Nutrition Examination Survey, we investigated
      inequalities in the diagnosis and management of hypertension and
      hypercholesterolemia among insured adults aged 20 to 64 years (n = 1,334). We
      assessed differences in insurance type (public, private) and routine place of
      care (yes, no), by sociodemographic characteristics. RESULTS: One in 10
      participants with hypertension and 3 in 10 with hypercholesterolemia were unaware
      and untreated. Having a routine place of care was associated with treatment and
      control of hypertension and with awareness, treatment, and control of
      hypercholesterolemia, after adjusting for insurance type, age, sex,
      race/ethnicity, foreign birth, income, and education. Differences in systolic
      blood pressure and total cholesterol between people with versus without a routine
      place of care were 2 to 3 times the difference found between people with public
      versus private insurance. Few differences were associated with sociodemographic
      characteristics after adjusting for routine place of care and insurance type;
      however, male sex, younger age, Asian race, and foreign birth with short-term US
      residence reduced the odds of having a routine place of care. Neither income nor
      education predicted having a routine place of care. CONCLUSION: Sociodemographic
      characteristics may influence chronic disease management among the insured
      through health care access factors such as having a routine place of care.

PMID- 21843413
TI  - Awareness of direct-to-consumer genetic tests and use of genetic tests among
      Puerto Rican adults, 2009.
AB  - INTRODUCTION: Genetic testing remains low among racial/ethnic minority
      populations in the United States. We aimed to determine the prevalence and
      correlates of awareness of direct-to-consumer (DTC) genetic tests and the
      prevalence of genetic test use in a population-based sample of adults in Puerto
      Rico. METHODS: We analyzed data from adults aged 18 years or older who completed
      information on genetic test awareness (n = 611; 96% of study population) from the
      Health Information National Trends Survey conducted in Puerto Rico in 2009. Odds
      ratios with 95% confidence intervals were estimated by using logistic regression
      models to identify factors associated with awareness of DTC genetic tests.
      RESULTS: The majority of respondents (56%) were aware of direct-to-consumer
      genetic tests, and approximately 4% had ever undergone any genetic test.
      Respondents who had never been married were less likely to be aware of DTC tests,
      as were current smokers. Respondents who ever sought cancer information were more
      likely to be aware of these tests. CONCLUSION: We provide the first published
      data on the awareness of DTC genetic tests and on use of genetic testing in
      Puerto Rico. Forty-four percent of our sample of Puerto Rican adults were unaware
      of direct-to-consumer genetic tests. Given the lack of clear benefits of DTC
      genetic tests to the general population, educational interventions should be
      developed to increase awareness and specific knowledge regarding the appropriate
      use of DTC genetic tests among people who are already aware of their existence.

PMID- 21843414
TI  - Strategies implemented by 20 local tobacco control agencies to promote smoke-free
      recreation areas, California, 2004-2007.
AB  - INTRODUCTION: Since 2000, local jurisdictions in California have enacted hundreds
      of policies and ordinances in an effort to protect their citizens from the
      harmful effects of secondhand smoke. We evaluated strategies used by state-funded
      local tobacco control programs to enact local smoke-free policies involving
      outdoor recreational spaces. METHODS: The Tobacco Control Evaluation Center
      analyzed 23 final evaluation reports that discussed adopting local smoke-free
      policies in outdoor recreational facilities in California. These reports were
      submitted for the 2004 through 2007 funding period by local tobacco control
      organizations to the California Department of Public Health, Tobacco Control
      Program. We used a comparative technique whereby we coded passages and compared
      them by locale and case, focusing on strategies that led to the enactment of
      smoke-free policies. RESULTS: Our analysis found the following 6 strategies to be
      the most effective: 1) having a "champion" who helps to carry an objective
      forward, 2) tapping into a pool of potential youth volunteers, 3) collecting and
      using local data as a persuasive tool, 4) educating the community in smoke-free
      policy efforts, 5) working strategically in the local political climate, and 6)
      framing the policy appropriately. CONCLUSION: These strategies proved effective
      regardless of whether policies were voluntary, administrative, or legislative.
      Successful policy enactment required a strong foundation of agency funding and an
      experienced and committed staff. These results should be relevant to other
      tobacco control organizations that are attempting to secure local smoke-free
      policy.

PMID- 21843416
TI  - Child care provider training and a supportive feeding environment in child care
      settings in 4 states, 2003.
AB  - INTRODUCTION: Strategies to prevent adult chronic diseases, including obesity,
      must start in childhood. Because many preschool-aged children spend mealtimes in
      child care facilities, staff should be taught supportive feeding practices for
      childhood obesity prevention. Higher obesity rates among low-income children
      suggest that centers providing care to these children require special attention.
      We compared self-reported feeding practices at child care centers serving low
      income children on the basis of whether they received funding and support from
      the Child and Adult Care Food Program (CACFP), which suggests supportive feeding
      practices. We also assessed training factors that could account for differences
      among centers. METHODS: Eligible licensed child care centers (n = 1600) from
      California, Colorado, Idaho, and Nevada received surveys. Of the 568 responding
      centers, 203 enrolled low-income families and served meals. We analyzed the
      responses of 93 directors and 278 staff for CACFP-funded centers and 110
      directors and 289 staff from nonfunded centers. Chi square analyses, pairwise
      comparisons, t tests, and multiple linear regressions were used to compare CACFP
      funded and nonfunded centers. RESULTS: Significant differences were noted in 10
      of 26 feeding practices between CACFP-funded and nonfunded centers. In each case,
      CACFP-funded centers reported practices more consistent with a supportive feeding
      environment. Forty-one percent of the variance could be explained by training
      factors, including who was trained, the credentials of those providing training,
      and the type of training. CONCLUSION: Our findings suggest that when trained by
      nutrition professionals, child care staff learn, adopt, and operationalize
      childhood obesity prevention feeding guidelines, thereby creating a supportive
      mealtime feeding environment.

PMID- 21843415
TI  - Physician visits and colorectal cancer testing among Medicare enrollees in North
      Carolina and South Carolina, 2005.
AB  - INTRODUCTION: Many Medicare enrollees do not receive colorectal cancer tests at
      recommended intervals despite having Medicare screening coverage. Little is known
      about the physician visits of Medicare enrollees who are untested. Our study
      objective was to evaluate physician visits of enrollees who lack appropriate
      testing to identify opportunities to increase colorectal cancer testing. METHODS:
      We used North Carolina and South Carolina Medicare data to compare type and
      frequency of physician visits for Medicare enrollees with and without a
      colorectal cancer test in 2005. Type of physician visit was defined by the
      physician specialty as primary care, mixed specialty (more than 1 specialty, 1 of
      which was primary care), and nonprimary care. We used multivariate modeling to
      assess the influence of type and frequency of physician visits on colorectal
      cancer testing. RESULTS: Approximately half (46.5%) of enrollees lacked
      appropriate colorectal cancer testing. Among the untested group, 19.8% had no
      physician visits in 2005. Enrollees with primary care visits were more likely to
      be tested than those without a primary care visit. Many enrollees who had primary
      care visits remained untested. Enrollees with visits to all physician types had a
      greater likelihood of having colorectal cancer testing. CONCLUSION: We identified
      3 categories of Medicare enrollees without appropriate colorectal cancer testing:
      those with no visits, those who see primary care physicians only, and those with
      multiple visits to physicians with primary and nonprimary care specialties.
      Different strategies are needed for each category to increase colorectal cancer
      testing in the Medicare population.

PMID- 21843417
TI  - Predictors of repeated PSA testing among black and white men from the Maryland
      Cancer Survey, 2006.
AB  - INTRODUCTION: Blacks have the highest incidence of and death from prostate cancer
      in the United States. Screening with prostate-specific antigen (PSA) may decrease
      mortality. Repeated testing allows for the calculation of PSA velocity (change of
      PSA over time), which may be a more clinically useful test for prostate cancer
      than a single PSA measurement. The objective of this study was to examine whether
      blacks were as likely as whites to report having had repeated PSA testing.
      METHODS: The Maryland Cancer Survey 2006 was a population-based, random-digit
      dialed statewide survey on cancer screening and risk behaviors of adults aged 40
      years or older. We analyzed self-reported information on repeated PSA testing (2
      PSA tests in the preceding 3 years) for 1,721 black and white men. We used
      logistic regression to estimate the effect of race and age on repeated PSA
      testing, adjusting for other covariates. RESULTS: Sixty-five percent of men
      reported ever having had a PSA test; 41% had repeated PSA testing in the past 3
      years. Blacks aged 40 to 49 were more likely to report having repeated PSA
      testing than whites in this age group (adjusted odds ratio [AOR], 3.3; 95%
      confidence interval [CI], 1.6-6.5). Blacks aged 60 to 69 were less likely to
      report repeated PSA testing than whites (AOR, 0.4, 95% CI, 0.2-0.8). No
      difference was seen by race among men aged 50 to 59 and men aged 70 or older.
      Repeated PSA testing was associated with living in an urban area and with having
      higher education, health insurance, a family history of prostate cancer, and
      having discussed cancer screening with a doctor. CONCLUSION: Self-reported
      repeated PSA testing differed by age and race, being higher among blacks aged 40
      to 49 and lower among blacks aged 60 to 69, compared with whites in their
      respective age groups.

PMID- 21843418
TI  - A midpoint process evaluation of the Los Angeles Basin Racial and Ethnic
      Approaches to Community Health Across the US (REACH US) Disparities Center, 2007
      2009.
AB  - BACKGROUND: Racial/ethnic minority groups have higher risks for disease resulting
      from obesity. COMMUNITY CONTEXT: The University of California, Los Angeles, and
      the Los Angeles County Department of Public Health partnered with community
      organizations to disseminate culturally targeted physical activity and nutrition
      based interventions in worksites. METHODS: We conducted community dialogues with
      people from 59 government and nonprofit health and social service agencies to
      develop wellness strategies for implementation in worksites. Strategies included
      structured group exercise breaks and serving healthy refreshments at
      organizational functions. During the first 2 years, we subcontracted with 6
      community-based organizations (primary partners) who disseminated these wellness
      strategies to 29 organizations within their own professional networks (secondary
      worksites) through peer modeling and social support. We analyzed data from the
      first 2 years of the project to evaluate our dissemination approach. OUTCOME:
      Primary partners had difficulty recruiting organizations in their professional
      network as secondary partners to adopt wellness strategies. Within their own
      organizations, primary partners reported significant increases in implementation
      in 2 of the 6 core organizational strategies for promoting physical activity and
      healthy eating. Twelve secondary worksites that completed organizational
      assessments on 2 occasions reported significant increases in implementation in 4
      of the 6 core organizational strategies. INTERPRETATION: Dissemination of
      organizational wellness strategies by trained community organizations through
      their existing networks (train-the-trainer) was only marginally successful.
      Therefore, we discontinued this dissemination approach and focused on recruiting
      leaders of organizational networks.

PMID- 21843419
TI  - Use of indoor tanning devices by high school students in the United States, 2009.
AB  - The objectives of this study were to provide estimates of indoor tanning device
      use among US high school students and provide baseline data before implementation
      of a 10% excise tax on indoor tanning device use mandated by recent federal
      health care reform legislation. We examined the frequency of indoor tanning
      device use by using data from the 2009 national Youth Risk Behavior Survey.
      Overall, 15.6% of students used an indoor tanning device during the 12 months
      before the survey; almost half of those students used an indoor tanning device 10
      or more times. Reported use and frequency of use varied by age, sex, and
      race/ethnicity. Given the high prevalence of indoor tanning device use among US
      high school students and the associated risk of melanoma, strategies to reduce
      exposure must be examined.

PMID- 21843420
TI  - Using a concept map as a tool for strategic planning: The Healthy Brain
      Initiative.
AB  - Concept mapping is a tool to assist in strategic planning that allows planners to
      work through a sequence of phases to produce a conceptual framework. Although
      several studies describe how concept mapping is applied to various public health
      problems, the flexibility of the methods used in each phase of the process is
      often overlooked. If practitioners were more aware of the flexibility, more
      public health endeavors could benefit from using concept mapping as a tool for
      strategic planning. The objective of this article is to describe how the 6
      concept-mapping phases originally outlined by William Trochim guided our
      strategic planning process and how we adjusted the specific methods in the first
      2 phases to meet the specialized needs and requirements to create The Healthy
      Brain Initiative: A National Public Health Road Map to Maintaining Cognitive
      Health. In the first stage (phases 1 and 2 of concept mapping), we formed a
      steering committee, convened 4 work groups over a period of 3 months, and
      generated an initial set of 42 action items grounded in science. In the second
      stage (phases 3 and 4), we engaged stakeholders in sorting and rating the action
      items and constructed a series of concept maps. In the third and final stage
      (phases 5 and 6), we examined and refined the action items and generated a final
      concept map consisting of 44 action items. We then selected the top 10 action
      items, and in 2007, we published The Healthy Brain Initiative: A National Public
      Health Road Map to Maintaining Cognitive Health, which represents the strategic
      plan for The Healthy Brain Initiative.

PMID- 21843421
TI  - Ethical concerns regarding interventions to prevent and control childhood
      obesity.

PMID- 21843422
TI  - Protecting children from harmful food marketing: options for local government to
      make a difference.
AB  - The obesity epidemic cannot be reversed without substantial improvements in the
      food marketing environment that surrounds children. Food marketing targeted to
      children almost exclusively promotes calorie-dense, nutrient-poor foods and takes
      advantage of children's vulnerability to persuasive messages. Increasing
      scientific evidence reveals potentially profound effects of food marketing on
      children's lifelong eating behaviors and health. Much of this marketing occurs in
      nationwide media (eg, television, the Internet), but companies also directly
      target children in their own communities through the use of billboards and
      through local environments such as stores, restaurants, and schools. Given the
      harmful effect of this marketing environment on children's health and the
      industry's reluctance to make necessary changes to its food marketing practices,
      government at all levels has an obligation to act. This article focuses on policy
      options for municipalities that are seeking ways to limit harmful food marketing
      at the community level.

PMID- 21843423
TI  - Childhood obesity: a framework for policy approaches and ethical considerations.
AB  - Although obesity rates among US children have increased during the past 3
      decades, effective public policies have been limited, and the quest for workable
      solutions raises ethical questions. To address these concerns, in 2010, the
      Robert Wood Johnson Foundation convened an expert panel to consider approaches to
      the ethics problems related to interventions for childhood obesity. On the basis
      of recommendations from the expert panel, we propose frameworks for policy
      approaches and ethical aspects of interventions and evaluation. We present these
      frameworks in the context of other papers in this collection and make
      recommendations for public health practice.

PMID- 21843424
TI  - Childhood obesity: issues of weight bias.
AB  - Although the effects of obesity on children's physical health are well
      documented, the social consequences of obesity are less well described and may
      not be addressed in intervention programs. Weight bias may take several forms. It
      may result in teasing and discrimination and may affect employment and
      educational opportunities. Health care providers may limit care of overweight or
      obese children. The media promote weight bias in multiple ways. Some parents are
      biased against their obese children. In an effort to avoid weight bias, new
      efforts to reduce obesity must be evaluated to determine whether these efforts
      do, in fact, add to the problem. It is important to understand that the weight
      bias that obese youth face is just as serious as the physical consequences of
      excessive weight on the welfare of the child.

PMID- 21843425
TI  - Children with special health care needs: acknowledging the dilemma of difference
      in policy responses to obesity.
AB  - Children with special health care needs (SHCN) account for part of the increasing
      prevalence of childhood obesity in the general population and can face an
      elevated risk for obesity. The federal government, in partnership with states,
      has assumed the role of steward for this vulnerable population and supports a
      network of services designed to promote their health through increased access to
      quality health services. Addressing obesity-related health risks among children
      with SHCN requires policies that support family- and community-based initiatives
      in addition to health services. We discuss the ethics of child obesity policy
      from the perspective of children with SHCN and their families, and identify
      salient issues to optimize benefits for children and families. We refer to the
      dilemma of difference to identify policy concerns that are specific to children
      with SHCN and ethically may require different approaches. Determining the
      appropriate mix of inclusive and special obesity prevention initiatives for
      children with SHCN and identifying approaches to ensure their full participation
      in community-based obesity prevention activities present challenges. Children
      with SHCN from low-income and minority communities are particularly vulnerable
      and warrant special attention.

PMID- 21843426
TI  - Public policy versus individual rights in childhood obesity interventions:
      perspectives from the Arkansas experience with Act 1220 of 2003.
AB  - Childhood obesity is a major public health problem. Experts recommend that
      prevention and control strategies include population-based policies. Arkansas Act
      1220 of 2003 is one such initiative and provides examples of the tensions between
      individual rights and public policy. We discuss concerns raised during the
      implementation of Act 1220 related to the 2 primary areas in which they emerged:
      body mass index measurement and reporting to parents and issues related to
      vending machine access. We present data from the evaluation of Act 1220 that have
      been used to address concerns and other research findings and conclude with a
      short discussion of the tension between personal rights and public policy. States
      considering similar policy approaches should address these concerns during policy
      development, involve multiple stakeholder groups, establish the legal basis for
      public policies, and develop consensus on key elements.

PMID- 21843427
TI  - A question of competing rights, priorities, and principles: a postscript to the
      Robert Wood Johnson Foundation symposium on the ethics of childhood obesity
      policy.

PMID- 21843428
TI  - The ethical basis for promoting nutritional health in public schools in the
      United States.
AB  - Schools may have an ethical obligation to act in response to the precipitous
      increase in the incidence of obesity among children. Using a bioethics framework,
      we present a rationale for school programs to improve the nutritional quality of
      students' diets. Because children are required to spend half their waking hours
      in school and because they consume a substantial portion of their daily food
      there, school is a logical focus for efforts to encourage healthy dietary
      behaviors to prevent obesity and its consequent individual and collective costs.
      We suggest that beyond strategic considerations, the concept of the common good
      justifies actions that may appear to conflict with freedom of choice of children,
      parents, and school staff, or with the interests of food and beverage companies.

PMID- 21843429
TI  - Ethical family interventions for childhood obesity.

PMID- 21843430
TI  - [Does free assumption of water from one hour after extubation reduce thirst
      without increasing complications in heart surgery patients?].
AB  - OBJECT: The aim of this study was to assess whether free assumption of water in
      heart surgery patients, as early as one hour after extubation, produces
      measurable differences in thirst, nausea and vomiting. METHODS: Randomized
      controlled trial (pilot phase), by sex and age. Eventual cases of dysphagia are
      identified by both a functional examination and a water test. The sense of thirst
      and sickness are registered 1 hour post-extubation and subsequently at the 3rd,
      6th and 12th hour using an NRS-scale 0-10. Data analysis was performed using a
      logistic regression model. RESULTS: 54 patients have been enrolled in the study.
      The sense of thirst is diminished in 17.39% of female, in 24.29% of male, leading
      to a total reduction in 22.58% of patients. The sense of sickness is arisen in
      13.04% of female, in 2.86% of male, leading to a total rise of 5.38% of patients.
      Moreover, the sensation of thirst is diminished in 33.33% of patients with free
      water intake (treatment group), but only in 16.07% of patients who cannot drink
      water (control group). Finally, as far as the sensation of sickness is concerned,
      our results show a rise of 11.11% in patients with free water intake, higher if
      compared to 1.79% of the control group, but smaller than the value indicated in
      the literature. DISCUSSION: The collected data showed that drinking water from
      one hour after extubation had a positive effect without a significant increase in
      the patient's perception of nausea.

PMID- 21843431
TI  - [Kangaroo Mother Care and conventional care: a review of literature].
AB  - Low birth weight is one of the major health problems throughout the world. All
      such neonates can benefit from an effective and efficient human care model -
      Kangaroo Mother Care. A review of the literature was performed to compare the
      short and long-term outcome of Kangaroo Mother Care to those of conventional care
      (incubator). Short-term outcome considered heart and breathing frequency,
      percutaneous oxygen saturation , transcutaneous oxygen pressure , body
      temperature, sleep-wake cycles, stress and pain. Long-term outcome considered
      mortality, somatic, psycho-motor and cognitive development, the incidence of
      infections and duration of hospitalization. Studies including pre-term neonates
      were also included. 19 of the 80 studies corresponded to the study criteria and
      demonstrated that Kangaroo Mother Care is important because it reduces pain and
      infections, shortens hospitalization, favors breast-feeding: in comparison to
      neonates treated conventionally, this method results in an earlier and better
      cognitive and motor development . Concerning body temperature, there were no
      differences with respect to traditional care. The literature shows that the
      Kangaroo Mother Care method can be a useful "adjunctive" strategy although
      further studies are necessary to clarify aspects such as heart and breathing rate
      and oxygen saturation that appear contradictory.

PMID- 21843432
TI  - [Nursing care of children by game-playing: a review of the literature].
AB  - Hospitalized children live a very critical period of their life, in which they
      prove the experience of separation from their own family, habits and toys. The
      nurse can use recreational activities to relate with children in a funny way.
      This recreational therapy represent a main up to date instrument for the nurse
      who works in paediatrics. Using the game children express themselves, their
      feelings and fears. They re-elaborate and understand the different situations
      they're living and relate with others. This happens normally in the daily life,
      but in particular during stressful situations such as, for example,
      hospitalization (Bianchi di Castelbianco et al., 2007). The purpose of this
      review of literature is to research if there is a connection between the
      recreational activities used by the nurse and pediatric nursing. The
      bibliographical review of this topic allows to describe the recreational
      activities available to the nurse and the way that these activities influence
      pediatric nursing. From this research, it results that the recreational
      activities can positively influence the ministering to needs of the hospitalized
      child.The specific training and putting into practice of up to date recreational
      activities, allow nurses to utilize this approach in pediatric nursing. Key
      words: Nursing care, pediatric nursing, hospitalized children, play, recreational
      activities.

PMID- 21843433
TI  - [Human resources management in a mother and child department: a research study on
      new nursing and obstetric staff].
AB  - To put "human resources" in the first place in a working context is an ambitious
      target. The basic idea is the give more value to the human and professional
      contribution of each individual in order to create an alliance between an
      organization and the people who work in it. In this context, the nursing
      coordinator plays a key role in inserting new staff. In this delicate phase, the
      expectations of new staff may or may not be fulfilled. The aim of the present
      study is to examine the possible difficulties that may occur during this phase.
      The study included 175 new staff and 175 nurses, obstetricians and pediatric
      nurses already at work for a total of 350. Research instruments consisted of two
      anonymous ad hoc questionnaires, the first issued to new staff at the Mother and
      Child Department, the second to staff already working in the same department.
      Results showed a lack of sensitivity towards new staff and a lack of dedicated
      procedures to help them during this delicate phase which is fundamental for their
      future career. Key words: newly assumed staff, work insertion, nurses.

PMID- 21843434
TI  - [Team building in health care by means of outdoor training. Evaluation of the
      experience of a Local Health Authority of Pinerolo].
AB  - It is always difficult to measure the quality and efficacy of a formative event.
      The event assessed in this study was an outdoor course and the aspects considered
      were the degree of satisfaction, the increase of knowledge, modifications in
      behavior and working actions and organized change (4 levels according to
      Kirkpatrick). Data were collected by means of a questionnaire which the 28 course
      participants were asked to fill in. Some aspects were statistically tested to
      evaluate eventual associations between the role of the participant and the answer
      given but these were not found to be significant. Results showed a good levels of
      satisfaction and knowledge increase which, in terms of working procedures and
      individual behavior, resulted in better team-building and mutual appreciation,
      whereas organizational changes were rather limited and sometimes reflected
      disappointment. The study made the Health Authority aware of the value of human
      resources and of the fact that a formative event which acts on feelings and
      behavior may be the key to success in bringing about deep and lasting changes.

PMID- 21843435
TI  - Alzheimer's care at home: a focus on caregivers strain.
AB  - The aging population is increasing worldwide. According to Italian authors, Italy
      is one of the leading and increasing aging populations in the world. Placing more
      numbers on the elderly increases the number of people who will live with dementia
      in the future and in our case of study, in an increase of people with Alzheimer's
      disease. Researchers have demonstrated that Alzheimer's disease comes with aging
      and it eventually affects the person's cognitive, emotional, and physical well
      being. Those who become diagnosed with Alzheimer's will eventually need
      assistance in their daily living, especially when it begins to progress to a
      higher stage. Daily assistance can come from staff at a hospital or from family
      members at home, but whether it is the patient's spouse or offspring, the person
      caring for the patient forms a burden of responsibility on themselves over time.
      The objective of this paper is to discuss and compare the effects of the burden
      placed on the Alzheimer's caregiver: sleep, anxiety and depression, stress, and
      use or nonuse of support services. The focus of this literature review is to
      submit what on the research of caregiver strain at home.

PMID- 21843436
TI  - [Treat to target in rheumatoid arthritis].

PMID- 21843437
TI  - [Carbapenems resistance in Pseudomonas aeruginosa during a 10-year period at
      Rawson Hospital].
AB  - BACKGROUNDS: Pae is a non-fermenting, Gram-negative bacillus that is associated
      with nosocomial infections and can easily be transmitted through the hands of
      health staff from patient to patient. Pae has a wide variety of natural
      resistance mechanisms and a great capacity to acquire new resistance mechanisms
      or to increase the expression of their natural resistance. Carbapenems resistance
      may be offered by impermeability mechanisms, increase in the efflux or enzymatic
      pump (production of carbapenemases). PURPOSE: To determine prevailing carbapenems
      resistance mechanisms in Pae and their evolution. MATERIALS AND METHODS: 372 Pae
      strains were collected during a ten-year period. The strains were identified
      through biochemical tests and performed a sensitivity test through diffusion and
      microbiological method. RESULTS: carbapenems resistance mechanisms for efflux in
      the year 2000 were , 50%; 2001 16.6%, 2002 6.3%, 2003 23.9%, 2004 18%, 2005 8.8%,
      2006 17.8%, 2007 31.8%, 2008 2.5%, 2009 5.2%. As regards impermeability: 2000
      33%, 2001 21.4%, 2002 8.5%, 2003 30.4%, 2004 14.7%, 2005 28.8%, 2006 23.5%, 2007
      13.6%, 2008 2.5%, 2009 5.2%. The microbiological test was negative for all
      studied strains. CONCLUSION: carbapenems resistance during this period was
      offered by impermeability and an increase in the expression of the efflux
      mechanism, not by enzymatic mechanism in our hospital. This is a very important
      issue from an epidemiological point of view because of the rapid horizontal
      transmission of the strains with this resistance mechanism.

PMID- 21843438
TI  - [Approximate entropy of the placebo effect in clinical trials of newer
      antidepressants].
AB  - Recent research concluded that antidepressant drugs are ineffective in treating
      moderate or severe depression. Statistically, there are no differences between
      the results with active drugs or placebo. Some authors have attributed this fail
      to variability or irregularity of the placebo effect in depressed patients or
      artifacts induced by meta-analysis. This fact highlights the difficulties faced
      by the research of psychoactive drugs in depression and revives the debate about
      the usefulness of the employ of placebo in these studies. This study aimed to
      determine the variability of the placebo effect in antidepressant clinical trials
      in simple linear and non-linear complex models. We performed a secondary analysis
      of data from 35 trials presented as evidence to the Food and Drug Administration
      (FDA) for approval of new generation antidepressants, all double-blind controlled
      with placebo in patients with unipolar mild or moderate depressive disorder,
      according to the criteria of "Diagnostic and Statistical Manual of Mental
      Disorders (DSM).Articles reviewed included 5133 patients . We have calculated the
      coefficient of variability, autocorrelation and approximate entropy of the
      placebo and treatment effects to determine whether the variability or regularity
      between different studies should be attributed to meta-analytical methods,
      placebo effect or ineffective treatment itself. The coefficient of variability in
      the placebo group was 26.49% and 18.81% in the treatment group. The placebo
      effect autocorrelation was within the confidential limits while the treatment
      group was outside showed cyclical variation. The approximate entropy value (ApEn
      N=35,m=2,R=2) in the placebo group was 0.5579 and 0.5744 in treatment group,
      leading to the conclusion that placebo effect is highly consistent and regular in
      complex non-linear models. The apparent variability of the placebo effect in
      depressed patients should be due to artifacts induced by simple linear models
      analysis.

PMID- 21843439
TI  - [Role of mitochondria and reactive oxygen species in the progression of heart
      failure].
AB  - Congestive heart failure (CHF) would be associated with mitochondrial
      abnormalities and increased of reactive species of oxygen (ROS). To clarify these
      issues we studied the structure, function of the mitochondrial enzyme nitro oxide
      synthase inducible (iNOS) and lipoperoxidation of membranes, one of their
      products through the peroxide nitrite ion (ONOO-), in the heart muscle of
      patients with heart failure congestive (ICC) grade III and IV (according to New
      York Heart Association). We included 25 patients who underwent cardiovascular
      surgery to biopsies of the heart muscle. They were stratified into a group with
      CHF (n = 18) and control group (n = 7). In di-chas biopsies analyzed the
      enzymatic activity of mitochondrial complex III spectrophotometrically, which was
      measured in mM.ubiquinona-1.mg prot, while the mitochondrial morphology was
      analyzed by the Zeiss electron microscope, the areas were quantified with program
      Axionvision 4.6. Lipoperoxidation of membranes was measured by the presence of
      ONOO-by immunohistochemistry against primary antibody against 3-nitrotyrosine was
      used lab kit system biogenic steptobidin biotin peroxidase (SBA) and coloring
      triamiobencidina (TAB), it is made with semicuantificacion intensity SCORE test.
      The statistical test used was ANOVA. The heart muscle of patients with CHF showed
      that the mitochondrial area was reduced by 78% compared with the control (160.37
      MUm2 +/- 9.87) (936.81 MUm2 +/- 78.48) p 0.0001. There was also a 70% reduction
      in complex III activity compared to control (1.9 10-2 mM ubiq.mim-prot 1.mg +/-
      12.6) (5.79 10-2mM ubiq.mim prot-1.mg +/- 36.6) p . The presence of ONOO-was
      significantly increased in patients with CHF. Alterations ultraestructutural and
      functional mitochondria found in patients with CHF and increased ROS are involved
      in the measures of physiopathology CCI and whites should be taken into account
      for future therapies of this condition.

PMID- 21843440
TI  - [Autoantibodies and systemic vasculitis].

PMID- 21843441
TI  - [The induced sputum allows guide a therapeutic strategy to control bronchial
      asthma].
AB  - In spite of physiopathogenic and therapeutic advances, asthma remains
      uncontrolled. The purpose of this test is to assess whether the instruments
      commonly used in the management of asthma are sufficient tools to control asthma,
      comparing the information provided by clinical evidence with cellular
      inflammatory parameters obtained through the analysis of induced sputum. We
      studied 15 asthmatics under treatment, which were evaluated the asthma control
      status (ACS) by clinical and spirometrical criteria, according to GINA
      recommendations. Then each patient underwent to obtain a sample of induced sputum
      (IE) and it was further analysed as a previously validated technique. From the
      total number of patients, 7 were total controlled patients according to ACS; only
      2 of them had a normal IE cellular pattern while the other 5 presented an
      inflammatory profile in the differential cells count of the IE, forced to make
      adjustments in the anti-inflammatory treatment. One partially controlled patient
      by ACS, revealed inflammatory parameters in IE allowing modify the therapeutic
      schema. In 7 not controlled patients by ACS, the cellular inflammatory
      characteristics in IE, allowed modify therapeutic strategy which achieved control
      of the disease. We concluded that inflamommetry by IE cellular analysis is the
      tool that contributes to optimize the treatment and achieve true control of the
      disease. We suggest including this procedure in clinical practice and proposing a
      strategy for the management of asthma.

PMID- 21843462
TI  - Fluorescence correlation spectroscopy of intact nuclear pore complexes.
AB  - No methods proposed thus far have the sensitivity to measure the transport of
      single molecules through single nuclear pore complexes (NPCs) in intact cells.
      Here we demonstrate that fluorescence correlation spectroscopy (FCS) combined
      with real-time tracking of the center of mass of single NPCs in live, unperturbed
      cells allows us to detect the transport of single molecules in a reference system
      of a pore with high temporal (millisecond) and spatial (limited by diffraction)
      resolution. We find that the transport of the classical receptor karyopherin
      beta1 (Kapbeta1) is regulated so as to produce a peculiar distribution of
      characteristic times at the NPC. This regulation, which is spatially restricted
      to the pore, depends on the properties and metabolic energy of Kapbeta1. As such,
      this method provides a powerful tool for studying nucleocytoplasmic shuttling at
      the nanometer scale under physiological conditions.

PMID- 21843463
TI  - Kinetic proofreading in chromatin remodeling: the case of ISWI/ACF.
AB  - For activation or repression of genes in eukaryotic organisms, the chromatin
      structure has to be adapted. This action is performed at least in part by
      dedicated motor proteins, the chromatin remodeling complexes. Recently,
      investigators have shown some interest in explaining how specific nucleosomes are
      targeted for chromatin remodeling. For this purpose, two kinetic proofreading
      scenarios for gene activation and repression have been put forward. We reanalyze
      both scenarios and show their common points and differences. Further, we propose
      that in gene repression by ISWI/ACF remodelers, which involves the generation of
      regular nucleosomal arrays, an additional proofreading step may be active.

PMID- 21843464
TI  - Computational electrophysiology: the molecular dynamics of ion channel permeation
      and selectivity in atomistic detail.

PMID- 21843465
TI  - Integral control of plant gravitropism through the interplay of hormone signaling
      and gene regulation.
AB  - The interplay between hormone signaling and gene regulatory networks is
      instrumental in promoting the development of living organisms. In particular,
      plants have evolved mechanisms to sense gravity and orient themselves
      accordingly. Here, we present a mathematical model that reproduces plant
      gravitropic responses based on known molecular genetic interactions for auxin
      signaling coupled with a physical description of plant reorientation. The model
      allows one to analyze the spatiotemporal dynamics of the system, triggered by an
      auxin gradient that induces differential growth of the plant with respect to the
      gravity vector. Our model predicts two important features with strong biological
      implications: 1), robustness of the regulatory circuit as a consequence of
      integral control; and 2), a higher degree of plasticity generated by the
      molecular interplay between two classes of hormones. Our model also predicts the
      ability of gibberellins to modulate the tropic response and supports the
      integration of the hormonal role at the level of gene regulation.

PMID- 21843466
TI  - Spacing of integrin ligands influences signal transduction in endothelial cells.
AB  - The physical attributes of the extracellular matrix play a key role in
      endothelium function by modulating the morphology and phenotype of endothelial
      cells. Despite the recognized importance of matrix-cell interactions, it is
      currently not known how the arrangement of adhesive ligands affects the
      morphology, signal transduction processes, and migration of endothelial cells. We
      aimed to study how endothelial cells respond to the average spatial arrangement
      of integrin ligands. We designed functionalized silicon surfaces with average
      spacing ranging from nanometers to micrometers of the peptide arginine-glycine
      aspartic acid (RGD). We found that endothelial cells adhered to and spread on
      surfaces independently of RGD-to-RGD spacing. In contrast, organization within
      focal adhesions (FAs) was extremely sensitive to ligand spacing, requiring a
      nanoscaled average RGD spacing of 44 nm to form lipid raft domains at FAs. The
      localized membrane organization strongly correlated with the signaling
      efficiencies of integrin activation and regulated vascular endothelial growth
      factor (VEGF)-induced signaling events. Importantly, this modulation in signal
      transduction directly affected the migratory ability of endothelial cells. We
      conclude that endothelial cells sense nanoscaled variations in the spacing of
      integrin ligands, which in turn influences signal transduction processes. Average
      RGD spacing similar to that found in fibronectin leads to lipid raft accumulation
      at FAs, enhances sensitivity to VEGF stimulation, and controls migration in
      endothelial cells.

PMID- 21843467
TI  - On the origin of order in the genome organization of ssRNA viruses.
AB  - Single-stranded RNA (ssRNA) viruses form a major class that includes important
      human, animal, and plant pathogens. While the principles underlying the
      structures of their protein capsids are generally well understood, much less is
      known about the organization of their encapsulated genomic RNAs. Cryo-electron
      microscopy and x-ray crystallography have revealed striking evidence of order in
      the packaged genomes of a number of ssRNA viruses. The physical determinants of
      such order, however, are largely unknown. We study here the relative effect of
      different energetic contributions, as well as the role of confinement, on the
      genome packaging of a representative ssRNA virus, the bacteriophage MS2, via a
      series of biomolecular simulations in which different energy terms are
      systematically switched off. We show that the bimodal radial density profile of
      the packaged genome is a consequence of RNA self-repulsion in confinement,
      suggesting that it should be similar for all ssRNA viruses with a comparable
      ratio of capsid size/genome length. In contrast, the detailed structure of the
      outer shell of the RNA density depends crucially on steric contributions from the
      capsid inner surface topography, implying that the various different polyhedral
      RNA cages observed in experiment are largely due to differences in the inner
      surface topography of the capsid.

PMID- 21843468
TI  - Estimating the synaptic current in a multiconductance AMPA receptor model.
AB  - Synaptic transmission starts after the presynaptic neuron has released diffusing
      neurotransmitters, leading to postsynaptic receptor activation and a postsynaptic
      current, mostly mediated by glutamatergic (AMPARs) receptors for excitatory
      neurons. Despite intense experimental and theoretical research, it is still
      unclear how factors such as the synaptic cleft geometry, the organization, the
      number and the multiconductance state of receptors, the geometry of postsynaptic
      density (PSD), and the neurotransmitter release location, shape the mean and the
      variance of the postsynaptic current and its plastic changes. To estimate the
      synaptic current amplitude and to account for the stochastic nature of synaptic
      transmission, we develop a semianalytical method in which we obtain a general
      expression for the coefficient of variation. The method uses the experimental
      data about the multiconductance channels. We find that PSD morphological changes
      can significantly modulate the synaptic current, which is maximally reliable (the
      coefficient of variation is minimal) for an optimal size of the PSD, that depends
      on the vesicular release active zone. We show that this optimal PSD size is due
      to nonlinear phenomena involving the receptor multibinding cooperativity. We
      conclude that changes in the PSD geometry can sustain a form of synaptic
      plasticity, independent of a change in the number of receptors.

PMID- 21843469
TI  - On depolarization-evoked exocytosis as a function of calcium entry: possibilities
      and pitfalls.
AB  - Secretion from many endocrine cells is a result of calcium-regulated exocytosis
      due to Ca2+ influx. Using the patch-clamp technique, voltage pulses can be
      applied to the cells to open Ca2+ channels, resulting in a measurable Ca2+
      current, and evoke exocytosis, which can be seen as an increase in membrane
      capacitance. A common tool for evaluating the relation between Ca2+ influx and
      exocytosis is to plot the increase in capacitance (DeltaC(m)) as a function of
      the integral of the measured Ca2+current (Q). When depolarizations of different
      lengths are imposed, the rate of exocytosis is typically higher for shorter than
      for longer pulses, which has been suggested to result from depletion of a granule
      pool or from Ca2+ current inactivation. It is here demonstrated that DeltaC(m) as
      a function of Q can reveal whether Ca2+ current inactivation masquerades as pool
      depletion. Moreover, it is shown that a convex, cooperativity-like, relation
      between DeltaC(m) and Q surprisingly cannot occur as a result of cooperative
      effects, but can result from delays in the exocytotic process or in Ca2+dynamics.
      An overview of expected DeltaC(m)-versus-Q relations for a range of explicit
      situations is given, which should help in the interpretation of data of
      depolarization-evoked exocytosis in endocrine cells.

PMID- 21843470
TI  - Fragmentation is crucial for the steady-state dynamics of actin filaments.
AB  - Despite the recognition that actin filaments are important for numerous cellular
      processes, and decades of investigation, the dynamics of in vitro actin filaments
      are still not completely understood. Here, we follow the time evolution of the
      length distribution of labeled actin reporter filaments in an unlabeled F-actin
      solution via fluorescence microscopy. Whereas treadmilling and diffusive length
      fluctuations cannot account for the observed dynamics, our results suggest that
      at low salt conditions, spontaneous fragmentation is crucial.

PMID- 21843471
TI  - Computational electrophysiology: the molecular dynamics of ion channel permeation
      and selectivity in atomistic detail.
AB  - Presently, most simulations of ion channel function rely upon nonatomistic
      Brownian dynamics calculations, indirect interpretation of energy maps, or
      application of external electric fields. We present a computational method to
      directly simulate ion flux through membrane channels based on biologically
      realistic electrochemical gradients. In close analogy to single-channel
      electrophysiology, physiologically and experimentally relevant timescales are
      achieved. We apply our method to the bacterial channel PorB from pathogenic
      Neisseria meningitidis, which, during Neisserial infection, inserts into the
      mitochondrial membrane of target cells and elicits apoptosis by dissipating the
      membrane potential. We show that our method accurately predicts ion conductance
      and selectivity and elucidates ion conduction mechanisms in great detail. Handles
      for overcoming channel-related antibiotic resistance are identified.

PMID- 21843472
TI  - Extracellular potassium inhibits Kv7.1 potassium channels by stabilizing an
      inactivated state.
AB  - Kv7.1 (KCNQ1) channels are regulators of several physiological processes
      including vasodilatation, repolarization of cardiomyocytes, and control of
      secretory processes. A number of Kv7.1 pore mutants are sensitive to
      extracellular potassium. We hypothesized that extracellular potassium also
      modulates wild-type Kv7.1 channels. The Kv7.1 currents were measured in Xenopus
      laevis oocytes at different concentrations of extracellular potassium (1-50 mM).
      As extracellular potassium was elevated, Kv7.1 currents were reduced
      significantly more than expected from theoretical calculations based on the
      Goldman-Hodgkin-Katz flux equation. Potassium inhibited the steady-state current
      with an IC(50) of 6.0 +/- 0.2 mM. Analysis of tail-currents showed that potassium
      increased the fraction of channels in the inactivated state. Similarly, the
      recovery from inactivation was slowed by potassium, suggesting that extracellular
      potassium stabilizes an inactivated state in Kv7.1 channels. The effect of
      extracellular potassium was absent in noninactivating Kv7.1/KCNE1 and Kv7.1/KCNE3
      channels, further supporting a stabilized inactivated state as the underlying
      mechanism. Interestingly, coexpression of Kv7.1 with KCNE2 did not attenuate the
      inhibition by potassium. In a number of other Kv channels, including Kv1.5,
      Kv4.3, and Kv7.2-5 channels, currents were only minimally reduced by an increase
      in extracellular potassium as expected. These results show that extracellular
      potassium modulates Kv7.1 channels and suggests that physiological changes in
      potassium concentrations may directly control the function of Kv7.1 channels.
      This may represent a novel regulatory mechanism of excitability and of potassium
      transport in tissues expressing Kv7.1 channels.

PMID- 21843473
TI  - Structural plasticity in self-assembling transmembrane beta-sheets.
AB  - Here we test the hypothesis that membrane-spanning beta-sheets can exhibit
      structural plasticity in membranes due to their ability to shift hydrogen-bonding
      patterns. Transmembrane beta-sheet forming peptides of the sequence AcWL(n),
      where n = 5, 6, or 7, which range from 21 to 27 A in maximum length, were
      incorporated into bilayers made of phosphatidylcholine lipids with saturated acyl
      chains containing 14, 16, or 18 carbons, which are 36-50 A in thickness. The
      effect of the peptide beta-sheets on fluid- and gel-phase bilayers were studied
      with differential scanning calorimetry and circular dichroism spectroscopy. We
      show that AcWL5 forms a stable, peptide-rich gel phase in all three lipids. The
      whole family of AcWL(n) peptides appears to form similarly stable, nonmembrane
      disrupting beta-sheets in all bilayer phases and thicknesses. Bilayers containing
      up to 20 mol % peptide, which is the maximum concentration tested, formed gel
      phases with melting temperatures that were equal to, or slightly higher than, the
      pure lipid transitions. Given the range of peptide lengths and bilayer
      thicknesses tested, these experiments show that the AcWL(n) family of membrane
      inserted beta-sheets exhibit remarkable structural plasticity in membranes.

PMID- 21843474
TI  - Phase-separation and domain-formation in cholesterol-sphingomyelin mixture: pulse
      EPR oxygen probing.
AB  - Membranes made of Chol/ESM (cholesterol/egg sphingomyelin) mixtures were
      investigated using saturation-recovery electron paramagnetic resonance spin
      labeling methods, in which bimolecular collisions of relaxation agents (oxygen or
      nickel ethylenediamine diacetic acid) with spin labels are measured. Liquid
      disordered (l(d)) and liquid-ordered (l(o)) phases, and cholesterol bilayer
      domains (CBDs) were discriminated and characterized by profiles of the oxygen
      transport parameter (OTP). In the l(d) phase, coexisting with the l(o) phase, the
      OTP profile is bell-shaped and lies above that in the pure ESM membrane. Changes
      in the OTP profile across the l(o) phase are complex. When the l(o) phase
      coexists with the l(d) phase, the OTP profile is similar to that across the pure
      ESM membrane but with a steeper bell shape. With an increase in cholesterol
      concentration (up to the cholesterol-solubility threshold), the profile becomes
      rectangular, with low OTP values from the membrane surface to the depth of C9,
      and high values in the membrane center. This approximately threefold increase in
      the OTP occurs at the depth at which the rigid ring structure of cholesterol is
      immersed. Further addition of cholesterol and the formation of the CBD does not
      affect the OTP profile across the l(o) phase. OTP values in the CBD are
      significantly lower than in the l(o) phase.

PMID- 21843475
TI  - Alcohol's effects on lipid bilayer properties.
AB  - Alcohols are known modulators of lipid bilayer properties. Their biological
      effects have long been attributed to their bilayer-modifying effects, but
      alcohols can also alter protein function through direct protein interactions.
      This raises the question: Do alcohol's biological actions result predominantly
      from direct protein-alcohol interactions or from general changes in the membrane
      properties? The efficacy of alcohols of various chain lengths tends to exhibit a
      so-called cutoff effect (i.e., increasing potency with increased chain length,
      which that eventually levels off). The cutoff varies depending on the assay, and
      numerous mechanisms have been proposed such as: limited size of the alcohol
      protein interaction site, limited alcohol solubility, and a chain-length
      dependent lipid bilayer-alcohol interaction. To address these issues, we
      determined the bilayer-modifying potency of 27 aliphatic alcohols using a
      gramicidin-based fluorescence assay. All of the alcohols tested (with chain
      lengths of 1-16 carbons) alter the bilayer properties, as sensed by a bilayer
      spanning channel. The bilayer-modifying potency of the short-chain alcohols
      scales linearly with their bilayer partitioning; the potency tapers off at higher
      chain lengths, and eventually changes sign for the longest-chain alcohols,
      demonstrating an alcohol cutoff effect in a system that has no alcohol-binding
      pocket.

PMID- 21843476
TI  - Theoretical and computational modeling of target-site search kinetics in vitro
      and in vivo.
AB  - Access to genetically encoded data depends on the dynamics of DNA-binding
      proteins searching for specific target sites in the genome. This search process
      is thought to occur by facilitated diffusion-a combination of three-dimensional
      diffusion and one-dimensional sliding. Although facilitated diffusion is capable
      of significantly speeding up the search in vitro, the importance of this
      mechanism in vivo remains unclear. We use numeric simulations and analytical
      theory to model the target-search dynamics of DNA-binding proteins under a wide
      range of conditions. Our models reproduce experimental measurements of search
      rate enhancement within bulk in vitro experiments, as well as the target search
      time for transcription factors measured in vivo. We find that facilitated
      diffusion can accelerate the search process only for a limited range of
      parameters and only under dilute DNA conditions. We address the role of DNA
      configuration and confinement, demonstrating that facilitated diffusion does not
      speed up the search on coiled versus straight DNA. Furthermore, we show that,
      under in vivo conditions, the search process becomes effectively diffusive and is
      independent of DNA configuration. We believe our results cast in a new light the
      role of facilitated diffusion in DNA targeting kinetics within the cell.

PMID- 21843477
TI  - PicoNewton-millisecond force steps reveal the transition kinetics and mechanism
      of the double-stranded DNA elongation.
AB  - We study the kinetics of the overstretching transition in lambda-phage double
      stranded (ds) DNA from the basic conformation (B state) to the 1.7-times longer
      and partially unwound conformation (S state), using the dual-laser optical
      tweezers under force-clamp conditions at 25 degrees C. The unprecedented
      resolution of our piezo servo-system, which can impose millisecond force steps of
      0.5-2 pN, reveals the exponential character of the elongation kinetics and allows
      us to test the two-state nature of the B-S transition mechanism. By analyzing the
      load-dependence of the rate constant of the elongation, we find that the
      elementary elongation step is 5.85 nm, indicating a cooperativity of ~25
      basepairs. This mechanism increases the free energy for the elementary reaction
      to ~94 k(B)T, accounting for the stability of the basic conformation of DNA, and
      explains why ds-DNA can remain in equilibrium as it overstretches.

PMID- 21843478
TI  - Electrostatic braiding and homologous pairing of DNA double helices.
AB  - Homologous pairing and braiding (supercoiling) have crucial effects on genome
      organization, maintenance, and evolution. Generally, the pairing and braiding
      processes are discussed in different contexts, independently of each other.
      However, analysis of electrostatic interactions between DNA double helices
      suggests that in some situations these processes may be related. Here we present
      a theory of DNA braiding that accounts for the elastic energy of DNA double
      helices as well as for the chiral nature of the discrete helical patterns of DNA
      charges. This theory shows that DNA braiding may be affected, stabilized, or even
      driven by chiral electrostatic interactions. For example, electrostatically
      driven braiding may explain the surprising recent observation of stable pairing
      of homologous double-stranded DNA in solutions containing only monovalent salt.
      Electrostatic stabilization of left-handed braids may stand behind the chiral
      selectivity of type II topoisomerases and positive plasmid supercoiling in
      hyperthermophilic bacteria and archea.

PMID- 21843479
TI  - The growth of sickle hemoglobin polymers.
AB  - The measurement of polymer growth is an essential element in characterization of
      assembly. We have developed a precise method of measuring the growth of sickle
      hemoglobin polymers by observing the time required for polymers to traverse a
      photolytically produced channel between a region in which polymers are created
      and a detection region. The presence of the polymer is functionally detected by
      observing its ability to create new polymers through the well-established process
      of heterogeneous nucleation. Using this method, we have determined the rate
      constants for monomer addition to and release from polymer ends, as well as their
      temperature dependences. At 25 degrees C we find k(+) = 84 +/- 2 mM-1 s-1 and k(
      ) = 790 +/- 80 molecules/s from each end. These numbers are in accord with
      differential interference contrast measurements, and their ratio gives a
      solubility measured on individual fibers. The single-fiber solubility agrees with
      that measured in sedimentation experiments. The concentration dependence of the
      monomer addition rate is consistent with monomer addition, but not oligomer
      addition, to growing polymers. The concentration dependence suggests the presence
      of an activation enthalpy barrier, and the rate of monomer addition is not
      diffusion-limited. Analysis of the temperature dependence of the monomer addition
      rate reveals an apparent activation energy of 9.1 +/- 0.6 kcal/mol.

PMID- 21843480
TI  - Prediction of hydrodynamic and other solution properties of rigid proteins from
      atomic- and residue-level models.
AB  - Here we extend the ability to predict hydrodynamic coefficients and other
      solution properties of rigid macromolecular structures from atomic-level
      structures, implemented in the computer program HYDROPRO, to models with lower,
      residue-level resolution. Whereas in the former case there is one bead per
      nonhydrogen atom, the latter contains one bead per amino acid (or nucleotide)
      residue, thus allowing calculations when atomic resolution is not available or
      coarse-grained models are preferred. We parameterized the effective hydrodynamic
      radius of the elements in the atomic- and residue-level models using a very large
      set of experimental data for translational and rotational coefficients (intrinsic
      viscosity and radius of gyration) for >50 proteins. We also extended the
      calculations to very large proteins and macromolecular complexes, such as the
      whole 70S ribosome. We show that with proper parameterization, the two levels of
      resolution yield similar and rather good agreement with experimental data. The
      new version of HYDROPRO, in addition to considering various computational and
      modeling schemes, is far more efficient computationally and can be handled with
      the use of a graphical interface.

PMID- 21843481
TI  - Automated real-space refinement of protein structures using a realistic backbone
      move set.
AB  - Crystals of many important biological macromolecules diffract to limited
      resolution, rendering accurate model building and refinement difficult and time
      consuming. We present a torsional optimization protocol that is applicable to
      many such situations and combines Protein Data Bank-based torsional optimization
      with real-space refinement against the electron density derived from
      crystallography or cryo-electron microscopy. Our method converts moderate- to low
      resolution structures at initial (e.g., backbone trace only) or late stages of
      refinement to structures with increased numbers of hydrogen bonds, improved
      crystallographic R-factors, and superior backbone geometry. This automated method
      is applicable to DNA-binding and membrane proteins of any size and will aid
      studies of structural biology by improving model quality and saving considerable
      effort. The method can be extended to improve NMR and other structures. Our
      backbone score and its sequence profile provide an additional standard tool for
      evaluating structural quality.

PMID- 21843482
TI  - Toward a predictive understanding of slow methyl group dynamics in proteins.
AB  - The development of the most recent generation of molecular mechanics force fields
      promises an increasingly predictive understanding of the protein dynamics
      function relationship. Based on extensive validation against various types of
      experimental data, the AMBER force field ff99SB was benchmarked in recent years
      as a favorable force field for protein simulations. Recent improvements of the
      side chain and backbone potentials, made by different groups, led to the ff99SB
      ILDN and ff99SBnmr1 force fields, respectively. The combination of these
      potentials into a unified force field, termed ff99SBnmr1-ILDN, was used in this
      study to perform a microsecond time scale molecular dynamics simulation of free
      ubiquitin in explicit solvent for validation against an extensive set of
      experimental NMR methyl group residual dipolar couplings. Our results show a high
      level of consistency between the experimental data and the values predicted from
      the molecular dynamics trajectory reflecting a systematically improved
      performance of ff99SBnmr1-ILDN over the original ff99SB force field. Moreover,
      the unconstrained ff99SBnmr1-ILDN MD ensemble achieves a similar level of
      agreement as the recently introduced EROS ensemble, which was constructed based
      on a large body of NMR data as constraints, including the methyl residual dipolar
      couplings. This suggests that ff99SBnmr1-ILDN provides a high-quality
      representation of the motions of methyl-bearing protein side chains, which are
      sensitive probes of protein-protein and protein-ligand interactions.

PMID- 21843483
TI  - Contribution of proteoglycan osmotic swelling pressure to the compressive
      properties of articular cartilage.
AB  - The negatively charged proteoglycans (PG) provide compressive resistance to
      articular cartilage by means of their fixed charge density (FCD) and high osmotic
      pressure (pi(PG)), and the collagen network (CN) provides the restraining forces
      to counterbalance pi(PG). Our objectives in this work were to: 1), account for
      collagen intrafibrillar water when transforming biochemical measurements into a
      FCD-pi(PG) relationship; 2), compute pi(PG) and CN contributions to the
      compressive behavior of full-thickness cartilage during bovine growth (fetal,
      calf, and adult) and human adult aging (young and old); and 3), predict the
      effect of depth from the articular surface on pi(PG) in human aging.
      Extrafibrillar FCD (FCD(EF)) and pi(PG) increased with bovine growth due to an
      increase in CN concentration, whereas PG concentration was steady. This
      maturation-related increase was amplified by compression. With normal human
      aging, FCD(EF) and pi(PG) decreased. The pi(PG)-values were close to equilibrium
      stress (sigma(EQ)) in all bovine and young human cartilage, but were only
      approximately half of sigma(EQ) in old human cartilage. Depth-related variations
      in the strain, FCD(EF), pi(PG), and CN stress profiles in human cartilage
      suggested a functional deterioration of the superficial layer with aging. These
      results suggest the utility of the FCD-pi(PG) relationship for elucidating the
      contribution of matrix macromolecules to the biomechanical properties of
      cartilage.

PMID- 21843484
TI  - Do hydration dynamics follow the structural perturbation during thermal
      denaturation of a protein: a terahertz absorption study.
AB  - We investigate the thermal denaturation of human serum albumin and the associated
      solvation using terahertz (THz) spectroscopy in aqueous buffer solution. Far- and
      near-ultraviolet circular dichroism spectroscopy reveal that the protein
      undergoes a native (N) to extended (E) state transition at temperature <=55
      degrees C with a marginal change in the secondary and tertiary structure. At 70
      degrees C, the protein transforms into an unfolded (U) state with significant
      irreversible disruption of its structures. We measure the concentration- and
      temperature-dependent THz absorption coefficient (alpha) of the protein solution
      using a p-Ge THz difference spectrometer (2.1-2.8 THz frequency range), thereby
      probing the collective protein-water network dynamics. When the solvated protein
      is heated up to 55 degrees C and cooled down again, a reversible change in THz
      absorption is observed. When increasing the temperature up to 70 degrees C, we
      find a dramatic irreversible change of THz absorption. The increase in THz
      absorption compared to bulk water is attributed to a blue shift in the spectrum
      of the solvated protein compared to bulk water. This is supported by measurements
      of THz absorption coefficients using THz time-domain spectroscopy (0.1-1.2 THz
      frequency range). We also use picosecond-resolved fluorescence spectroscopy of
      the tryptophan 214 moiety of human serum albumin. All experimental observations
      can be explained by a change in the hydration dynamics of the solvated protein
      due to the additional exposure of hydrophobic residues upon unfolding.

PMID- 21843485
TI  - Molecular adaptation of photoprotection: triplet states in light-harvesting
      proteins.
AB  - The photosynthetic light-harvesting systems of purple bacteria and plants both
      utilize specific carotenoids as quenchers of the harmful (bacterio)chlorophyll
      triplet states via triplet-triplet energy transfer. Here, we explore how the
      binding of carotenoids to the different types of light-harvesting proteins found
      in plants and purple bacteria provides adaptation in this vital photoprotective
      function. We show that the creation of the carotenoid triplet states in the light
      harvesting complexes may occur without detectable conformational changes, in
      contrast to that found for carotenoids in solution. However, in plant light
      harvesting complexes, the triplet wavefunction is shared between the carotenoids
      and their adjacent chlorophylls. This is not observed for the antenna proteins of
      purple bacteria, where the triplet is virtually fully located on the carotenoid
      molecule. These results explain the faster triplet-triplet transfer times in
      plant light-harvesting complexes. We show that this molecular mechanism, which
      spreads the location of the triplet wavefunction through the pigments of plant
      light-harvesting complexes, results in the absence of any detectable chlorophyll
      triplet in these complexes upon excitation, and we propose that it emerged as a
      photoprotective adaptation during the evolution of oxygenic photosynthesis.

PMID- 21843486
TI  - Nanoparticle diffusion measures bulk clot permeability.
AB  - A clot's function is to achieve hemostasis by resisting fluid flow. Permeability
      is the measurement of a clot's hemostatic potential. It is sensitive to a wide
      range of biochemical parameters and pathologies. In this work, we consider the
      hydrodynamic phenomenon that reduces the mobility of fluid near the fiber
      surfaces. This no-slip boundary condition both defines the gel's permeability and
      suppresses nanoparticle diffusion in gel interstices. Here we report that, unlike
      previous work where steric effects also hindered diffusion, our system
      nanoparticles in fibrin gel-was subject exclusively to hydrodynamic diffusion
      suppression. This result enabled an automated, high-throughput permeability assay
      that used small clot volumes. Permeability was derived from nanoparticle
      diffusion using the effective medium theory, and showed one-to-one correlation
      with measured permeability. This technique measured permeability without
      quantifying gel structure, and may therefore prove useful for characterizing
      similar materials (e.g., extracellular matrix) where structure is uncontrolled
      during polymerization and difficult to measure subsequently. We also report that
      PEGylation reduced, but did not eliminate, the population of immobile particles.
      We studied the forces required to pull stuck PEG particles free to confirm that
      the attachment is a result of neither covalent nor strong electrostatic binding,
      and discuss the relevance of this force scale to particle transport through
      physiological clots.

PMID- 21843487
TI  - Multiple replica repulsion technique for efficient conformational sampling of
      biological systems.
AB  - Here, we propose a technique for sampling complex molecular systems with many
      degrees of freedom. The technique, termed "multiple replica repulsion" (MRR),
      does not suffer from poor scaling with the number of degrees of freedom
      associated with common replica exchange procedures and does not require sampling
      at high temperatures. The algorithm involves creation of multiple copies
      (replicas) of the system, which interact with one another through a repulsive
      potential that can be applied to the system as a whole or to portions of it. The
      proposed scheme prevents oversampling of the most populated states and provides
      accurate descriptions of conformational perturbations typically associated with
      sampling ground-state energy wells. The performance of MRR is illustrated for
      three systems of increasing complexity. A two-dimensional toy potential surface
      is used to probe the sampling efficiency as a function of key parameters of the
      procedure. MRR simulations of the Met-enkephalin pentapeptide, and the 76-residue
      protein ubiquitin, performed in presence of explicit water molecules and totaling
      32 ns each, investigate the ability of MRR to characterize the conformational
      landscape of the peptide, and the protein native basin, respectively. Results
      obtained for the enkephalin peptide reflect more closely the extensive
      conformational flexibility of this peptide than previously reported simulations.
      Those obtained for ubiquitin show that conformational ensembles sampled by MRR
      largely encompass structural fluctuations relevant to biological recognition,
      which occur on the microsecond timescale, or are observed in crystal structures
      of ubiquitin complexes with other proteins. MRR thus emerges as a very promising
      simple and versatile technique for modeling the structural plasticity of complex
      biological systems.

PMID- 21843488
TI  - Analysis of red-fluorescent proteins provides insight into dark-state conversion
      and photodegradation.
AB  - Fluorescent proteins (FPs) are powerful tools that permit real-time visualization
      of cellular processes. The utility of a given FP for a specific experiment
      depends strongly on its effective brightness and overall photostability. However,
      the brightness of FPs is limited by dark-state conversion (DSC) and irreversible
      photobleaching, which occur on different timescales. Here, we present in vivo
      ensemble assays for measuring DSC and irreversible photobleaching under
      continuous and pulsed illumination. An analysis of closely related red FPs
      reveals that DSC and irreversible photobleaching are not always connected by the
      same mechanistic pathway. DSC occurs out of the first-excited singlet state, and
      its magnitude depends predominantly on the kinetics for recovery out of the dark
      state. The experimental results can be replicated through kinetic simulations of
      a four-state model of the electronic states. The methodology presented here
      allows light-driven dynamics to be studied at the ensemble level over six orders
      of magnitude in time (microsecond to second timescales).

PMID- 21843489
TI  - Stoichiometry of reconstituted high-density lipoproteins in the hydrated state
      determined by photon antibunching.
AB  - Apolipoprotein A-I plays a central role in the solution structure of high-density
      lipoproteins. Determining the stoichiometry of lipid-bound apo A-I in the
      hydrated state is therefore fundamental to understanding how high-density
      lipoproteins form and function. Here, we use the quantum optical phenomenon of
      photon antibunching to determine the number of apo A-I molecules bound to
      discoidal lipoproteins and compare this with values obtained by photon-counting
      histogram analysis. Both the photon antibunching and photon-counting analyses
      show that reconstituted high-density lipoprotein particles contain two apo A-I
      molecules, which is in agreement with the commonly accepted double-belt model.

PMID- 21843490
TI  - Single-molecule nanopositioning: structural transitions of a helicase-DNA complex
      during ATP hydrolysis.
AB  - The conformational states of Escherichia coli Rep helicase undergoing ATP
      hydrolysis while bound to a partial-duplex DNA (pdDNA) were studied using single
      molecule FRET. Crystallographic studies showed that Rep bound to single-stranded
      DNA can exist in open and closed conformations that differ in the orientation of
      the 2B subdomain. FRET measurements between eight Rep mutants donor-labeled at
      different residues and pdDNA acceptor-labeled at the junction were conducted at
      each of the four nucleotide states. The positions of donor-labeled residues,
      based on crystal structure, and FRET measurements between these donor molecules
      and the acceptor fluorophore at the DNA junction were used to predict the most
      likely position for the DNA junction using a triangulation algorithm. These
      predicted junction positions are compared with the crystal structure to determine
      whether the open or closed conformation is more consistent with the FRET data.
      Our data revealed that there are two distinct Rep-pdDNA conformations in the
      ATPgammaS and ADP states, an unexpected finding. The primary conformation is
      similar to that observed in nucleotide-free and ADP.Pi states, and the secondary
      conformation is a novel conformation where the duplex DNA and 2B subdomain moved
      as a unit by 13 A relative to the rest of the protein. The primary conformation
      found in all nucleotide states is consistent with the closed conformation of the
      crystal structure however; the secondary conformation is a new conformation that
      has not been observed before. We discuss the possible implications of this newly
      observed conformation.

PMID- 21843491
TI  - Rapid and quantitative imaging of excitation polarized fluorescence reveals
      ordered septin dynamics in live yeast.
AB  - We report an imaging method for fast, sensitive analysis of the orientation of
      fluorescent molecules by employing a liquid-crystal based universal polarizer in
      the optical path of a wide-field light microscope. We developed specific
      acquisition and processing algorithms for measuring the anisotropy and for
      correcting artifacts caused by fluorescence bleaching, background light, and
      differential transmission of optical components. We call this approach the
      Fluorescence LC-PolScope and we used it to analyze the architectural dynamics of
      septin-green fluorescent protein (septin-GFP) constructs in the neck region of
      budding yeast. We describe three different states of highly anisotropic septin
      arrays in which the prevailing orientation of GFP dipoles was either parallel or
      perpendicular to the mother-bud axis. The transitions between these ordered
      states were characterized by transient isotropic states. To analyze the patterns
      of polarized fluorescence, we modeled the alignment of septin-GFP constructs in
      different stages of septin ring formation. Based on our model, our experimental
      data are consistent with the formation of paired rather than single filaments and
      the axis of the alpha-helical septin terminus linked to a GFP molecule is likely
      oriented normal to the cell surface. The Fluorescence LC-PolScope combines the
      molecular specificity of fluorescence tagging with the structural specificity of
      polarized light analysis.

PMID- 21843492
TI  - Real-time vibrational dynamics in chlorophyll a studied with a few-cycle pulse
      laser.
AB  - We use a 6.8-fs laser as the light source for broad-band femtosecond pump-probe
      real-time vibrational spectroscopy to investigate both electronic relaxation and
      vibrational dynamics of the Q(y)-band of Chl-a at 293 K. More than 25 vibrational
      modes coupled to the Q(y) transition are observed. Eleven of them have been
      clarified predominantly due to the excited state, and six of them are concluded
      to be nearly exclusively resulting from the ground-state wave-packet motion.
      Moreover, thanks to the broad-band detection over 5000 cm-1, the modulated
      signals due to the excited state vibrational coherence are observed on both sides
      of the 0-0 transition with equal separation. The corresponding nonlinear process
      has been studied using a three-level model, from which the probe wavelength
      dependence of the phase of the periodic modulation can be calculated. The probe
      wavelength dependence of the vibrational amplitude is interpreted in terms of the
      interaction between the "pump" or "laser," Stokes, and anti-Stokes field
      intermediated by the molecular vibrations. In addition, an excited state
      absorption peak at ~709 nm has been observed. To the best of our knowledge, this
      is the first study of broad-band real-time vibrational spectroscopy in Chl-a.

PMID- 21843493
TI  - Flow of excitation energy in the cryptophyte light-harvesting antenna phycocyanin
      645.
AB  - We report a detailed description of the energy migration dynamics in the
      phycocyanin 645 (PC645) antenna complex from the photosynthetic alga Chroomonas
      CCMP270. Many of the cryptophyceae are known to populate greater depths than most
      other algal families, having developed a 99.5% efficient light-harvesting system.
      In this study, we used femtosecond time-resolved spectroscopy and global analysis
      to characterize the excited-state dynamics of PC645. Several different pump
      colors were selected to excite different fractions of the four phycobiliprotein
      pairs present in the complex. Measurements were also performed at cryogenic
      temperature to enhance spectral resolution and selectively promote downhill
      energy transfers. Upon excitation of the highest-energy bilins
      (dihydrobiliverdins), energy is transferred from the core of the complex to the
      periphery within 0.82 ps. Four bilins (mesobiliverdin (MBV) A/B and
      phycocyanobilins (PCB) 158C/D), which are responsible for the central band of the
      absorption spectrum, show concerted spectral dynamics. These chromophores show a
      biphasic decay with lifetimes of 0.6 ps (MBV) and 5-7 ps (PCB 158) to the lowest
      bilin pair (PCB 82C/D) absorbing around 650-657 nm. Within this lifetime of
      several picoseconds, the excitations reach the PCB 82 bilins on the two poles at
      the smaller sides of PC645. A slow 44-46 ps energy transfer step to the lowest
      energy PCB 82 bilin concludes the dynamics.

PMID- 21843494
TI  - Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in
      patients with chronic pancreatitis.
AB  - BACKGROUND & AIMS: A randomized trial that compared endoscopic and surgical
      drainage of the pancreatic duct in patients with advanced chronic pancreatitis
      reported a significant benefit of surgery after a 2-year follow-up period. We
      evaluated the long-term outcome of these patients after 5 years. METHODS: Between
      2000 and 2004, 39 symptomatic patients were randomly assigned to groups that
      underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009,
      information was collected regarding pain, quality of life, morbidity, mortality,
      length of hospital stay, number of procedures undergone, changes in pancreatic
      function, and costs. Analysis was performed according to an intention-to-treat
      principle. RESULTS: During the 79-month follow-up period, one patient was lost
      and 7 died from unrelated causes. Of the patients treated by endoscopy, 68%
      required additional drainage compared with 5% in the surgery group (P = .001).
      Hospital stay and costs were comparable, but overall, patients assigned to
      endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of
      the patients in the endoscopy group eventually underwent surgery. Although the
      mean difference in Izbicki pain scores was no longer significant (39 vs 22; P =
      .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042).
      Levels of quality of life and pancreatic function were comparable. CONCLUSIONS:
      In the long term, symptomatic patients with advanced chronic pancreatitis who
      underwent surgery as the initial treatment for pancreatic duct obstruction had
      more relief from pain, with fewer procedures, than patients who were treated
      endoscopically. Importantly, almost half of the patients who were treated with
      endoscopy eventually underwent surgery.

PMID- 21843495
TI  - Peripheral blood lymphocyte and monocyte recovery and survival in acute leukemia
      postmyeloablative allogeneic hematopoietic stem cell transplant.
AB  - Many previous studies of immune reconstitution (IR) postallogeneic hematopoietic
      stem cell transplantation (HSCT) have focused on lymphocyte recovery. Recognizing
      that IR involves complex interactions between innate and adaptive immune
      networks, we hypothesized that patterns of both monocyte and lymphocyte recovery
      could provide additional prognostic information. To test our hypothesis, we
      analyzed data from 135 consecutive patients undergoing myeloablative allogeneic
      HSCT for acute myeloid (AML) and lymphoblastic leukemia (ALL) from 2001 to 2010.
      The absolute lymphocyte and monocyte counts (ALC and AMC, respectively) were
      determined longitudinally at days +15, +30, +60, and +100, and correlated with
      clinical outcomes. At the day +30 time point, both ALC and AMC >0.3 * 10(9)
      cells/L were strongly associated with improved survival (overall survival [OS]
      29.6 months versus 5.4 months, P = .006 and 25.3 months versus 5.1 months, P =
      .01 respectively), a pattern that generally continued through the day +100
      evaluation. Multivariate analysis revealed the following independent prognostic
      factors: early disease status at transplantation, the development of chronic
      GVHD, the day +30 AMC, day +100 AMC, and day +100 ALC. To further explore whether
      any inherent patterns in the timing of lymphocyte and monocyte recovery had
      prognostic value post-HSCT, we performed unsupervised hierarchical clustering on
      the longitudinal hematopoietic parameters studied in this cohort. Four clusters
      of patients were identified: clusters A-D. Patient clusters B and D both
      demonstrated improved ALC and AMC recovery at the day +60 and day +100 time
      points and had significantly improved OS compared with clusters A and C (57.8
      months versus 19.7 and 4.4 months, respectively, P < .001). Our data suggest that
      patients with poor lymphocyte and monocyte recovery beyond the day +60 time
      points may be at risk for poorer outcomes, and that further investigation into
      lymphoid/myeloid interactions in developing individualized immunotherapy is
      warranted.

PMID- 21843497
TI  - Desiccating stress induces CD4+ T-cell-mediated Sjogren's syndrome-like corneal
      epithelial apoptosis via activation of the extrinsic apoptotic pathway by
      interferon-gamma.
AB  - We investigated the role of CD4(+) T-cell-produced interferon (IFN)-gamma on
      corneal epithelial apoptosis in a murine desiccating stress (DS) model that
      resembles Sjogren's syndrome. The DS model was generated in C57BL/6 (B6) and B6
      IFN-gamma-knockout (B6gammaKO) mice. Adoptive transfer of CD4(+) T cells from DS
      exposed donor to recombination activating gene (RAG)-1(-/-) recipient mice and
      topical neutralization of IFN-gamma were performed to determine whether IFN-gamma
      produced by pathogenic CD4(+) T cells promotes corneal epithelial apoptosis.
      Apoptosis in corneal epithelia was assessed by evaluating the expression and
      activity of caspases 3, 8, and 9. The activation of caspase-8 mediated increased
      corneal epithelial apoptosis in B6 mice after DS, and this was exacerbated by
      subconjunctival IFN-gamma injection. B6gammaKO mice were resistant to DS-induced
      apoptosis; however, B6gammaKO mice receiving IFN-gamma developed apoptosis
      similar to that observed in B6 wild-type mice. Adoptive transfer of CD4(+) T
      cells from donors subjected to DS increased corneal epithelial apoptosis via
      activation of caspase-8 in recipients, similar to that in the donor mice. Topical
      neutralization of IFN-gamma in adoptive transfer recipients decreased corneal
      epithelial apoptosis. DS, IFN-gamma administration, or CD4(+) T-cell adoptive
      transfer had no effect on the expression and activation of the intrinsic
      apoptosis mediator, caspase-9. CD4(+) T-cell-produced IFN-gamma plays a pivotal
      role in DS-induced corneal epithelial apoptosis via activation of the extrinsic
      apoptotic pathway.

PMID- 21843496
TI  - A detrimental role for invariant natural killer T cells in the pathogenesis of
      experimental dengue virus infection.
AB  - Dengue virus (DENV), a member of the mosquito-borne flaviviruses, is a serious
      public health problem in many tropical countries. We assessed the in vivo
      physiologic contribution of invariant natural killer T (iNKT) cells, a population
      of nonconventional lipid-reactive alphabeta T lymphocytes, to the host response
      during experimental DENV infection. We used a mouse-adapted DENV serotype 2
      strain that causes a disease that resembles severe dengue in humans. On DENV
      challenge, splenic and hepatic iNKT cells became activated insofar as CD69 and
      Fas ligand up-regulation and interferon-gamma production. C57BL/6 mice deficient
      in iNKT cells (Jalpha18(-/-)) were more resistant to lethal infection than were
      wild-type animals, and the phenotype was reversed by adoptive transfer of iNKT
      cells to Jalpha18(-/-) animals. The absence of iNKT cells in Jalpha18(-/-) mice
      was associated with decreased systemic and local inflammatory responses, less
      liver injury, diminished vascular leak syndrome, and reduced activation of
      natural killer cells and neutrophils. iNKT cell functions were not necessary for
      control of primary DENV infection, after either natural endogenous activation or
      exogenous activation with the canonical iNKT cell agonist alpha
      galactosylceramide. Together, these data reveal a novel and critical role for
      iNKT cells in the pathogenesis of severe experimental dengue disease.

PMID- 21843498
TI  - Substituted tryptophans at amyloid-beta(1-40) residues 19 and 20 experience
      different environments after fibril formation.
AB  - Amyloid-beta protein (Abeta) is the principal component of the neuritic plaques
      found in Alzheimer's disease. The predominant Abeta morphology in the plaques is
      fibrillar which has prompted substantial in vitro work to better understand the
      molecular organization of Abeta fibrils. In the current study, tryptophan
      substitutions were made at Abeta(1-40) position 19 (F19W) or 20 (F20W) to
      ascertain environmental differences between the two residues in the fibril
      structure. Kinetic studies revealed similar rates of fibril formation between
      Abeta(1-40) F19W and F20W and both peptides formed typical amyloid fibril
      structures. Abeta(1-40) F19W fibrils displayed a significant tryptophan
      fluorescence blue-shift in lambda(max) (33nm) compared to monomer while Abeta(1
      40) F20W fibrils had a much smaller shift (9nm). Fluorescence quenching
      experiments with water-soluble acrylamide and KI demonstrated that both W19 and
      W20 were much less accessible to quenching in fibrils compared to monomer. Lipid
      soluble TEMPO quenched the fluorescence of Abeta(1-40) F19W fibrils more
      effectively than F20W fibrils in agreement with the fluorescence blue-shift
      results. These findings demonstrate distinct environments between Abeta(1-40)
      residues 19 and 20 fibrils and indicate that while W20 accessibility is
      compromised in Abeta fibrils it resides in a much less hydrophobic environment
      than W19.

PMID- 21843499
TI  - Blocking Daxx trafficking attenuates neuronal cell death following
      ischemia/reperfusion in rat hippocampus CA1 region.
AB  - Previous studies have shown that the death-associated protein (Daxx) shuttles
      between nucleus and cytoplasm under ischemic stress, and the subcellular
      localization of Daxx plays an important role in ischemic neuron death. In this
      study, by blocking the Daxx trafficking, the rat hippocampus CA1 neurons were
      protected against cerebral ischemia/reperfusion, and the molecular mechanism
      underlying this neuroprotection was studied. We found that pretreatment of
      SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), or an anti-oxidant, N
      acetylcysteine (NAC), could not only prevent Daxx from trafficking but also
      increase the number of the surviving CA1 pyramidal cells of hippocampus at 5days
      of reperfusion. Furthermore, knock-down of endogenous Daxx exerted similar
      neuroprotective effect during ischemia/reperfusion. We found the treatment of
      SP600125 or NAC could decrease the activation of Ask1 during ischemia/reperfusion
      and suppress the assembly of the Fas.Daxx.Ask1 signaling module, and in
      succession inhibit JNK activation and c-Jun phosphorylation. This study provides
      the Daxx trafficking as a new potential therapeutic target for ischemic brain
      injury.

PMID- 21843500
TI  - Free cholesterol accumulation impairs antioxidant activities and aggravates
      apoptotic cell death in menadione-induced oxidative injury.
AB  - Although the relationship between hypercholesterolemia and oxidative stress has
      been extensively investigated, direct evidence regarding to the roles of
      cholesterol accumulation in the generations of reactive oxygen species (ROS) and
      apoptotic cell death under oxidative stress is lack. In this study, we
      investigated productions of superoxide anions (O(2)(-)) and nitric oxide (NO),
      and apoptotic cell death in wild type Chinese hamster ovary (CHO) cells and
      cholesterol accumulated CHO cells genetically and chemically. Oxidative stress
      was induced by menadione challenge. The results revealed that abundance of free
      cholesterol (FC) promoted menadione-induced O(2)(-) and NO productions. FC
      accumulation down-regulated eNOS expression but up-regulated NADPH oxidases, and
      inhibited the activities of superoxide dismutase (SOD) and catalase. Treatment of
      menadione increased the expressions of iNOS and qp91 phox, enhanced the
      activities of SOD and catalase in the wild-type CHO cells but inhibited the
      activity of glutathione peroxidase in the cholesterol accumulated CHO cells.
      Moreover, FC abundance promoted apoptotic cell death in these cells. Taken
      together, those results suggest that free cholesterol accumulation aggravates
      menadione-induced oxidative stress and exacerbates apoptotic cell death.

PMID- 21843501
TI  - Thermal, dynamic and structural properties of drug AT1 antagonist olmesartan in
      lipid bilayers.
AB  - It is proposed that AT1 antagonists (ARBs) exert their biological action by
      inserting into the lipid membrane and then diffuse to the active site of AT1
      receptor. Thus, lipid bilayers are expected to be actively involved and play a
      critical role in drug action. For this reason, the thermal, dynamic and
      structural effects of olmesartan alone and together with cholesterol were studied
      using differential scanning calorimetry (DSC), 13C magic-angle spinning (MAS)
      nuclear magnetic resonance (NMR), cross-polarization (CP) MAS NMR, and Raman
      spectroscopy as well as small- and wide angle X-ray scattering (SAXS and WAXS) on
      dipalmitoyl-phosphatidylcholine (DPPC) multilamellar vesicles. 13C CP/MAS spectra
      provided direct evidence for the incorporation of olmesartan and cholesterol in
      lipid bilayers. Raman and X-ray data revealed how both molecules modify the
      bilayer's properties. Olmesartan locates itself at the head-group region and
      upper segment of the lipid bilayers as 13C CP/MAS spectra show that its presence
      causes significant chemical shift changes mainly in the A ring of the steroidal
      part of cholesterol. The influence of olmesartan on DPPC/cholesterol bilayers is
      less pronounced. Although, olmesartan and cholesterol are residing at the same
      region of the lipid bilayers, due to their different sizes, display distinct
      impacts on the bilayer's properties. Cholesterol broadens significantly the main
      transition, abolishes the pre-transition, and decreases the membrane fluidity
      above the main transition. Olmesartan is the only so far studied ARB that
      increases the gauche:trans ratio in the liquid crystalline phase. These
      significant differences of olmesartan may in part explain its distinct
      pharmacological profile.

PMID- 21843502
TI  - Coarse grained model for exploring voltage dependent ion channels.
AB  - The relationship between the membrane voltage and the gating of voltage activated
      ion channels and other systems have been a problem of great current interest.
      Unfortunately, reliable molecular simulations of external voltage effects present
      a major challenge, since meaningful converging microscopic simulations are not
      yet available and macroscopic treatments involve major uncertainties in terms of
      the dielectric used and other key features. This work extends our coarse grained
      (CG) model to simulations of membrane/protein systems under external potential.
      Special attention is devoted to a consistent modeling of the effect of external
      potential due to the electrodes, emphasizing semimacroscopic description of the
      electrolytes in the solution regions between the membranes and the electrodes, as
      well as the coupling between the combined potential from the electrodes plus the
      electrolytes and the protein ionized groups. We also provide a clear connection
      to microscopic treatment of the electrolytes and thus can explore possible
      conceptual problems that are hard to resolve by other current approaches. For
      example, we obtain a clear description of the charge distribution in the entire
      electrolyte system, including near the electrodes in membrane/electrodes systems
      (where continuum models do not seem to provide the relevant results).
      Furthermore, the present treatment provides an insight on the distribution of the
      electrolyte charges before and after equilibration across the membrane, and thus
      on the nature of the gating charge. The different aspects of the model have been
      carefully validated by considering problems ranging for the simple Debye-Huckel,
      and the Gouy-Chapman models to the evaluation of the electrolyte distribution
      between two electrodes, as well as the effect of extending the simulation system
      by periodic replicas. Overall the clear connection to microscopic descriptions
      combined with the power of the CG modeling seems to offer a powerful tool for
      exploring the balance between the protein conformational energy and the
      interaction with the external potential in voltage activated channels. To
      illustrate these features we present a preliminary study of the gating charge in
      the voltage activated Kv1.2 channel, using the actual change in the electrolyte
      charge distribution rather than the conventional macroscopic estimate. We also
      discuss other special features of the model, which include the ability to capture
      the effect of changes in the protonation states of the protein residues during
      the close to open voltage induced transition. This article is part of a Special
      Issue entitled: Membrane protein structure and function.

PMID- 21843504
TI  - Testin, a novel binding partner of the calcium-sensing receptor, enhances
      receptor-mediated Rho-kinase signalling.
AB  - The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis
      and the regulation of other cellular functions including cell proliferation and
      cytoskeletal organisation. The multifunctional nature of the CaR is manifested
      through ligand-dependent stimulation of different signalling pathways that are
      also regulated by partner binding proteins. Following a yeast two-hybrid library
      screen using the intracellular tail of the CaR as bait, we identified several
      novel binding partners including the focal adhesion protein, testin. Testin has
      not previously been shown to interact with cell surface receptors. The sites of
      interaction between the CaR and testin were mapped to the membrane proximal
      region of the receptor tail and the second zinc-finger of LIM domain 1 of testin,
      the integrity of which was found to be critical for the CaR-testin interaction.
      The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation
      and confocal microscopy studies. Ectopic expression of testin in HEK293 cells
      stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect
      on CaR-stimulated ERK signalling. These results suggest an interplay between the
      CaR and testin in the regulation of CaR-mediated Rho signalling with possible
      effects on the cytoskeleton.

PMID- 21843503
TI  - Water wires in atomistic models of the Hv1 proton channel.
AB  - The voltage-gated proton channel (Hv1) is homologous to the voltage-sensing
      domain (VSD) of voltage-gated potassium (Kv) channels but lacks a separate pore
      domain. The Hv1 monomer has dual functions: it gates the proton current and also
      serves as the proton conduction pathway. To gain insight into the structure and
      dynamics of the yet unresolved proton permeation pathway, we performed all-atom
      molecular dynamics simulations of two different Hv1 homology models in a lipid
      bilayer in excess water. The structure of the Kv1.2-Kv2.1 paddle-chimera VSD was
      used as template to generate both models, but they differ in the sequence
      alignment of the S4 segment. In both models, we observe a water wire that extends
      through the membrane, whereas the corresponding region is dry in simulations of
      the Kv1.2-Kv2.1 paddle-chimera. We find that the kinetic stability of the water
      wire is dependent upon the identity and location of the residues lining the
      permeation pathway, in particular, the S4 arginines. A measurement of water
      transport kinetics indicates that the water wire is a relatively static feature
      of the permeation pathway. Taken together, our results suggest that proton
      conduction in Hv1 may occur via Grotthuss hopping along a robust water wire, with
      exchange of water molecules between inner and outer ends of the permeation
      pathway minimized by specific water-protein interactions. This article is part of
      a Special Issue entitled: Membrane protein structure and function.

PMID- 21843505
TI  - Identification of the Drosophila and Tribolium receptors for the recently
      discovered insect RYamide neuropeptides.
AB  - One year ago, we discovered a new family of insect RYamide neuropeptides, which
      has the C-terminal consensus sequence FFXXXRYamide, and which is widely occurring
      in most insects, including the fruitfly Drosophila melanogaster and the red flour
      beetle Tribolium castaneum (F. Hauser et al., J. Proteome Res. 9 (2010) 5296
      5310). Here, we identify a Drosophila G-protein-coupled receptor (GPCR) coded for
      by gene CG5811 and its Tribolium GPCR ortholog as insect RYamide receptors. The
      Drosophila RYamide receptor is equally well activated (EC(50), 1*10(-9)M) by the
      two Drosophila RYamide neuropeptides: RYamide-1 (PVFFVASRYamide) and RYamide-2
      (NEHFFLGSRYamide), both contained in a preprohormone coded for by gene CG40733.
      The Tribolium receptor shows a somewhat higher affinity to Tribolium RYamide-2
      (ADAFFLGPRYamide; EC(50), 5*10(-9)M) than to Tribolium RYamide-1
      (VQNLATFKTMMRYamide; EC(50), 7*10(-8)M), which might be due to the fact that the
      last peptide does not completely follow the RYamide consensus sequence rule.
      There are other neuropeptides in insects that have similar C-terminal sequences
      (RWamide or RFamide), such as the FMRFamides, sulfakinins, myosuppressins,
      neuropeptides F, and the various short neuropeptides F. Amazingly, these
      neuropeptides show no cross-reactivity to the Tribolium RYamide receptor, while
      the Drosophila RYamide receptor is only very slightly activated by high
      concentrations (>10(-6)M) of neuropeptide F and short neuropeptide F-1, showing
      that the two RYamide receptors are quite specific for activation by insect
      RYamides, and that the sequence FFXXXRYamide is needed for effective insect
      RYamide receptor activation. Phylogenetic tree analyses and other amino acid
      sequence comparisons show that the insect RYamide receptors are not closely
      related to any other known insect or invertebrate/vertebrate receptors, including
      mammalian neuropeptide Y and insect neuropeptide F and short neuropeptide F
      receptors. Gene expression data published in Flybase (www.flybase.org) show that
      the Drosophila CG5811 gene is significantly expressed in the hindgut of adult
      flies, suggesting a role of insect RYamides in digestion or water reabsorption.

PMID- 21843506
TI  - Retraction notice to "Downregulation of citrin, a mitochondrial AGC, is
      associated with apoptosis of hepatocytes" [Biochem. Biophys. Res. Commun. 364
      (2007) 937-944].

PMID- 21843507
TI  - All-trans retinoic acid induces cellular senescence by up-regulating levels of
      p16 and p21 via promoter hypomethylation.
AB  - All-trans retinoic acid (ATRA) induces cellular senescence via up-regulation of
      p16 and p21; however, the action mechanism of ATRA is unknown. Here, we show that
      ATRA induces promoter hypomethylation of p16 and p21 via down-regulation of DNA
      methyltransferases 1, 3a, and 3b to facilitate binding of Ets1/2 to the p16
      promoter and p53 to the p21 promoter, resulting in up-regulation of their
      expression and subsequent induction of cellular senescence in HepG2 cells. These
      effects were mediated by retinoic acid receptor beta2 whose promoter was also
      hypomethylated in the presence of ATRA. Therefore, ATRA can be considered as an
      epi-drug in cancer therapy.

PMID- 21843508
TI  - Deletion of P399_E401 in NADPH cytochrome P450 oxidoreductase results in partial
      mixed oxidase deficiency.
AB  - P450 oxidoreductase (POR) is the electron donor for all microsomal P450s
      including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel
      POR mutation P399_E401del in two unrelated Turkish patients with 46,XX disorder
      of sexual development. Recombinant POR proteins were produced in yeast and tested
      for their ability to support steroid metabolizing P450 activities. In comparison
      to wild-type POR, the P399_E401del protein was found to decrease catalytic
      efficiency of 21-hydroxylation of progesterone by 68%, 17alpha-hydroxylation of
      progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%,
      aromatization of androstenedione by 85% and cytochrome c reduction activity by
      80%. Protein structure analysis of the three amino acid deletion P399_E401
      revealed reduced stability and flexibility of the mutant. In conclusion,
      P399_E401del is a novel mutation in POR that provides valuable genotype-phenotype
      and structure-function correlation for mutations in a different region of POR
      compared to previous studies. Characterization of P399_E401del provides further
      insight into specificity of different P450s for interaction with POR as well as
      nature of metabolic disruptions caused by more pronounced effect on specific
      P450s like CYP17A1 and aromatase.

PMID- 21843509
TI  - Remodeling of ribosomal genes in somatic cells by Xenopus egg extract.
AB  - Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei,
      however little is known about the earliest processes associated with the switch
      in the transcriptional program. We show here that an early reprogramming event is
      the remodeling of ribosomal chromatin and gene expression. This occurs within
      hours of extract treatment and is distinct from a stress response. Egg extract
      elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar
      remodeling involves a rapid and stable decrease in ribosomal gene transcription,
      and promoter targeting of the nucleolar remodeling complex component SNF2H
      without affecting occupancy of the transcription factor UBF and the stress
      silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF
      and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse
      effect on rDNA remodeling induced by extract and elicits a stress-type nuclear
      response. Thus, an early event of Xenopus egg extract-mediated nuclear
      reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling
      complex. Condition-specific and rapid silencing of ribosomal genes may serve as a
      sensitive marker for evaluation of various reprogramming methods.

PMID- 21843510
TI  - The N-terminal domain of alpha-dystroglycan, released as a 38 kDa protein, is
      increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
AB  - alpha-Dystroglycan is an extracellular adhesion protein that is known to interact
      with different ligands. The interaction is thought to stabilize the integrity of
      the plasma membrane. The N-terminal part of alpha-dystroglycan may be
      proteolytically processed to generate a small 38 kDa protein (alpha-DG-N). The
      physiological significance of alpha-DG-N is unclear but has been suggested to be
      involved in nerve regeneration and myelination and to function as a potential
      biomarker for neurodegenerative and neuromuscular diseases. In this report we
      show that alpha-DG-N is released into different body fluids, such as lachrimal
      fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the
      significance of alpha-DG-N in CSF we examined the levels of alpha-DG-N and known
      neurodegenerative markers in CSF from patients diagnosed with Lyme
      neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB
      patients, 67% showed a significant increase of CSF alpha-DG-N compared to healthy
      controls. After treatment with antibiotics the CSF alpha-DG-N levels were
      normalized in the LNB patients.

PMID- 21843511
TI  - Biochemical disorders associated with antiproliferative effect of
      dehydroepiandrosterone in hepatoma cells as revealed by LC-based metabolomics.
AB  - DHEA is known to have chemopreventive and antiproliferative activities, and was
      initially thought to be mediated by inhibition of G6PD. Our previous study has
      shown that DHEA may act through interference with energy metabolism. To study the
      effect of pharmacological dose of DHEA on cellular metabolism, and to further
      delineate the mechanism underlying its antiproliferative effect, we applied a
      metabolomic approach to globally profile the changes in metabolites in SK-Hep1
      cells underexpressing G6PD (Sk-Gi) and control cells (Sk-Sc) after DHEA
      treatment. RRLC-TOF-MS was used to identify metabolites, and tandem mass
      spectrometry was used to confirm their identity. DHEA induced changes in
      glutathione metabolism, lipid metabolism, s-adenosylmethionine (SAM) metabolism,
      as well as lysine metabolism. Elevation in level of glutathione disulfide,
      together with a concomitant decrease in level of reduced glutathione, was
      indicative of increased oxidative stress. Depletion of carnitine and its acyl
      derivatives reflected decline in fatty acid catabolism. These changes were
      associated with mitochondrial malfunction and reduction in cellular ATP content.
      Cardiolipin (CL) and phosphatidylcholine (PC) levels decreased significantly,
      suggesting that alterations in lipid composition are causally related to decline
      in mitochondrial function after DHEA treatment. The decline in cellular SAM
      content was accompanied by decreased expression of methionine adenosyltransferase
      genes MAT2A and MAT2B. SAM supplementation partially rescued cells from DHEA
      induced growth stagnation. Our findings suggest that DHEA causes perturbation of
      multiple pathways in cellular metabolism. Decreased SAM production, and
      cardiolipin depletion and the resulting mitochondrial dysfunction underlie the
      antiproliferative effect of DHEA.

PMID- 21843512
TI  - 15-Deoxy-Delta12,14-prostaglandin J2, an electrophilic lipid mediator of anti
      inflammatory and pro-resolving signaling.
AB  - 15-deoxy-Delta(12,14)-prostagandin J(2) (15d-PGJ2) is produced in the inflamed
      cells and tissues as a consequence of upregulation of cyclooxygenase-2 (COX-2).
      15d-PGJ2 is known to be the endogenous ligand of peroxisome proliferator
      activated receptor gamma (PPARgamma) with multiple physiological properties.
      Though one of the terminal products of the COX-2-catalyzed reactions, this
      cyclopentenone prostaglandin exerts potent anti-inflammatory actions, in part, by
      antagonizing the activities of pro-inflammatory transcription factors, such as NF
      kappaB, STAT3, and AP-1, while stimulating the anti-inflammatory transcription
      factor Nrf2. These effects are not necessarily dependent on its activation of
      PPARgamma, but often involves direct interaction with the above signaling
      molecules and their regulators. The locally produced 15d-PGJ2 is also involved in
      the resolution of inflammatory responses. Thus, 15d-PGJ2, especially formed
      during the late phase of inflammation, might inhibit cytokine secretion and other
      events by antigen-presenting cells like dendritic cells or macrophages. 15d-PGJ2
      can also affect the priming and effector functions of T lymphocytes and induce
      their apoptotic cell death. These represent a negative feedback explaining how
      once-initiated immunologic and inflammatory responses are switched off and
      terminated. In this context, 15d-PGJ2 and its synthetic derivatives have
      therapeutic potential for the treatment of inflammatory disorders.

PMID- 21843513
TI  - Intracellular ATP levels determine cell death fate of cancer cells exposed to
      both standard and redox chemotherapeutic agents.
AB  - Cancer cells generally exhibit high levels of reactive oxygen species (ROS) that
      stimulate cell proliferation and promote genetic instability. Since this
      biochemical difference between normal and cancer cells represents a specific
      vulnerability that can be selectively targeted for cancer therapy, various ROS
      generating agents are currently in clinical trials, either as single agents or in
      combination with standard therapy. However, little is known about the potential
      consequences of an increased oxidative stress for the efficacy of standard
      chemotherapeutic agents. In this context, we have assessed the influence of an
      oxidative stress generated by the combination of ascorbate and the redox-active
      quinone menadione on the capacity of melphalan, a common alkylating agent, to
      induce apoptosis in a chronic myelogenous leukemia cell line. Our data show that
      oxidative stress did not inhibit but rather promoted cancer cell killing by
      melphalan. Interestingly, we observed that, in the presence of oxidative stress,
      the type of cell death shifted from a caspase-3 dependent apoptosis to necrosis
      because of an ATP depletion which prevented caspase activation. Taken together,
      these data suggest that ROS-generating agents could be useful in combination with
      standard chemotherapy, even if all the molecular consequences of such an addition
      remain to be determined.

PMID- 21843514
TI  - Valproic acid utilizes the isoleucine breakdown pathway for its complete beta
      oxidation.
AB  - Valproic acid (VPA) is a simple branched medium-chain fatty acid with expanding
      therapeutic applications beyond its prime anticonvulsant properties. AIMS: (1) To
      resolve the underlying basis for the interference of valproate with the
      isoleucine degradative pathway and (2) to shed new light on the enzymology of the
      beta-oxidation pathway of valproate. METHODS: Urine organic acids were analyzed
      by gas chromatography/mass spectrometry. In vitro studies were performed with
      heterologously expressed human 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD)
      and fibroblasts from controls and a patient with MHBD deficiency using 2-methyl-3
      hydroxybutyryl-CoA and 3-hydroxyvalproyl-CoA as substrates. The respective
      enzymatic activities were measured using optimized HPLC procedures. Short-chain
      enoyl-CoA hydratase (ECHS1) immunoprecipitation in a human liver homogenate was
      performed and hydratase activity was measured in the supernatants by HPLC, using
      crotonyl-CoA and Delta(2(E))-valproyl-CoA as substrates. RESULTS: Patients on
      valproate therapy had a moderately increased urinary excretion of the isoleucine
      metabolite 2-methyl-3-hydroxybutyric acid. MHBD was found to convert 3
      hydroxyvalproyl-CoA into 3-ketovalproyl-CoA. MHBD activity in control fibroblasts
      was comparable using both 2-methyl-3-hydroxybutyryl-CoA and 3-hydroxyvalproyl-CoA
      as substrates. In fibroblasts of a patient with MHBD deficiency, there was no
      detectable MHBD activity when 3-hydroxyvalproyl-CoA was used as substrate.
      Samples with immunoprecipitated crotonase had no detectable hydratase activity
      using both crotonyl-CoA and Delta(2(E))-valproyl-CoA as substrates. DISCUSSION:
      This work demonstrates for the first time, that MHBD is the unique enzyme
      responsible for the dehydrogenation of 3-hydroxyvalproyl-CoA. Furthermore, we
      show that crotonase is the major, if not the single hydratase involved in VPA
      beta-oxidation, next to its role in isoleucine catabolism.

PMID- 21843515
TI  - Relevance of both type-1 and type-2 corticotropin releasing factor receptors in
      stress-induced relapse to cocaine seeking behaviour.
AB  - The essential role of corticotropin releasing factor (CRF) and its type-1
      receptor (CRF1) in stress-induced relapse to drug seeking has been demonstrated.
      The bed nucleus of the stria terminalis is the major anatomical substrate for
      this CRF/CRF1 receptor action. More recently, the role of type-2 CRF (CRF2)
      receptors in stress-induced relapse to cocaine seeking has also has been
      documented. The ventral tegmental area is the anatomical substrate for this
      CRF/CRF2 receptor action. The new information involving CRF2 receptors in stress
      induced relapse to cocaine seeking has generated a need for a reappraisal of the
      existing anatomical and pharmacological evidence that have been used to support
      the critical role of CRF1 receptors. The role of CRF2 receptors in stress-induced
      relapse to drug seeking also opens the question of the putative role of the other
      peptides of the CRH family (urocotin-1, urocortin-2 and urocortin-3) that have
      high affinity for CRF2 receptors. In this commentary, the available evidence
      supporting the role of both CRF1 and CRF2 receptors in stress-induced relapse to
      drug seeking is reviewed.

PMID- 21843516
TI  - Interferon-alpha2b and transforming growth factor-beta1 treatments on HCC cell
      lines: Are Wnt/beta-catenin pathway and Smads signaling connected in
      hepatocellular carcinoma?
AB  - Wnt/beta-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC).
      Activated beta-catenin accumulates in the cytosol and nucleus and forms a nuclear
      complex with TCF/LEF factors like TCF4. Interferon-alpha (IFN-alpha) has recently
      been recognized to harbor therapeutic potential in prevention and treatment of
      HCC. Transforming Growth Factor-beta1 (TGF-beta1) is a mediator of apoptosis,
      exerting its effects via Smads proteins. One mode of interaction between Wnt/beta
      catenin and TGF-beta1/Smads pathways is the association of Smads with beta
      catenin/TCF4. In this study we analyzed the effects of IFN-alpha2b and TGF-beta1
      treatments on Wnt/beta-catenin pathway, Smads proteins levels, beta
      catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A
      and Huh7 cell lines. IFN-alpha2b and TGF-beta1 attenuated Wnt/beta-catenin signal
      by decreasing beta-catenin and Frizzled7 receptor proteins contents and the
      interaction of beta-catenin with TCF4. Truncated beta-catenin form present in C3A
      cell line also diminished after treatments. Both cytokines declined Smads
      proteins and their interaction with TCF4. The overall cellular response to
      cytokines was the decrease in proliferation and increase in apoptotic death.
      Treatment with Wnt3a, which elevates beta-catenin protein levels, also generated
      the increment of Smads proteins contents when comparing with untreated cells. In
      conclusion, IFN-alpha2b and TGF-beta1 proved to be effective as modulators of
      Wnt/beta-catenin pathway in HCC cell lines holding both wild-type and truncated
      beta-catenin. Since the inhibition of beta-catenin/TCF4/Smads complexes formation
      may have a critical role in slowing down oncogenesis, IFN-alpha2b and TGF-beta1
      could be useful as potential treatments in patients with HCC.

PMID- 21843517
TI  - Impact of divalent metal ions on regulation of adenylyl cyclase isoforms by
      forskolin analogs.
AB  - Mammalian membranous adenylyl cyclases (mACs) play an important role in
      transmembrane signalling events in almost every cell and represent an interesting
      drug target. Forskolin (FS) is an invaluable research tool, activating AC
      isoforms 1-8. However, there is a paucity of AC isoform-selective FS analogs.
      Therefore, we examined the effects of FS and six FS derivatives on recombinant
      ACs 1, 2 and 5, representing members of different mAC families. Correlations of
      the pharmacological properties of the different AC isoforms revealed pronounced
      differences between ACs 1, 2 and 5. Additionally, potencies and efficacies of FS
      derivatives changed for any given AC isoform, depending on the metal ion, Mg(2+)
      or Mn(2+). The most striking effects of Mg(2+) and Mn(2+) on the diterpene
      profile were observed for AC2 where the large inhibitory effect of BODIPY-FS in
      the presence of Mg(2+) was considerably reduced in the presence of Mn(2+).
      Sequence alignment and docking experiments confirmed an exceptional position of
      AC2 compared to ACs 1 and 5 with respect to the structural environment of the
      catalytic core and cation-dependent diterpene effects. In conclusion, mAC
      isoforms 1, 2 and 5 exhibit a distinct pharmacological diterpene profile,
      depending on the divalent cation present. mAC crystal structures and
      modelling/docking studies provided an explanation for the pharmacological
      differences between the AC isoforms. Our study constitutes an important step
      towards the development of isoform-specific diterpenes exhibiting stimulatory or
      inhibitory effects.

PMID- 21843518
TI  - Comparison of two insulin assays for first-phase insulin release in type 1
      diabetes prediction and prevention studies.
AB  - BACKGROUND: Detection of below-threshold first-phase insulin release or FPIR (1+3
      minute insulin concentrations during an intravenous glucose tolerance test
      [IVGTT]) is important in type 1 diabetes prediction and prevention studies
      including the TrialNet Oral Insulin Prevention Trial. We assessed whether an
      insulin immunoenzymometric assay (IEMA) could replace the less practical but
      current standard of a radioimmunoassay (RIA) for FPIR. METHODS: One hundred
      thirty-three islet autoantibody positive relatives of persons with type 1
      diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both
      assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above
      threshold, uncertain) by the IEMA was derived and validated against FPIR by the
      RIA. RESULTS: The insulin IEMA-based rule accurately classified below- and above
      threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161
      (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was
      more likely among below-threshold vs above-threshold FPIRs by the RIA (64%
      [30/47] vs. 18% [21/114], respectively; p<0.05). CONCLUSIONS: An insulin IEMA for
      FPIR in subjects at risk for type 1 diabetes accurately determined below- and
      above-threshold FPIRs in 2/3 of tests relative to the current standard of the
      insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is
      limiting the insulin RIA for FPIR to the latter given the practical advantages of
      the more specific IEMA.

PMID- 21843519
TI  - Measurement of NT-proBNP with LOCI technology in heart failure patients.
AB  - OBJECTIVES: The aim of our study was to determine NT-proBNP concentrations in
      heart failure (HF) patients with a luminescent oxygen channeling immunoassay
      (LOCI). DESIGN AND METHODS: Seventy HF patients were enrolled. NT-proBNP levels
      were measured with LOCI method and compared to a reference NT-proBNP assay.
      RESULTS: LOCI NT-proBNP levels were significantly correlated with the reference
      NT-proBNP assay and were related to HF severity. CONCLUSIONS: LOCI assay
      demonstrates performances close to the comparative assay for NT-proBNP testing
      and allows a significant reduction of the time of analysis.

PMID- 21843520
TI  - Influence of temperature and period of freezing on the generation of hemolysate
      and blood cell lysate.
AB  - BACKGROUND: There is little information on temperature and period of freezing for
      generating hemolysate and blood cell lysate. MATERIALS AND METHODS: Primary tubes
      containing whole blood were frozen at -20 degrees C and -80 degrees C and then
      serially thawed to assess cell lysis and clinical chemistry tests in centrifuged
      plasma. RESULTS AND CONCLUSIONS: Massive amount of blood cells lysis could only
      be obtained by storing samples 12h at -20 degrees C, or 2h at -80 degrees C.

PMID- 21843521
TI  - The association between ACE polymorphism and risk of colorectal cancer in a
      Chinese population.
AB  - OBJECTIVES: Angiotensin I-converting enzyme (ACE) plays crucial roles not only in
      the regulation of circulatory homeostasis but also in the pathology of
      carcinomas. An insertion-deletion (I/D) polymorphism in intron 16 of ACE gene was
      identified to be functional. We aimed to investigate the association between ACE
      I/D polymorphism and risk of colorectal cancer (CRC). DESIGN AND METHODS: Using
      genomic DNA from 241 CRC patients and 299 control subjects, we genotyped the ACE
      I/D polymorphism using a polymerase chain reaction analysis. RESULTS: We found
      that patients carrying the D allele were associated with an increased risk of
      developing poorly differentiated cancer and metastasis compared with those
      carrying the I allele (OR=1.54, 95%CI, 1.04-2.28; OR=1.56, 95%CI, 1.08-2.26,
      respectively), although no significant association was observed between cases and
      controls in overall analysis. CONCLUSIONS: These findings indicate that the ACE
      I/D polymorphism is likely to play a role in CRC progression.

PMID- 21843522
TI  - Tumor-induced osteomalacia: The tumor may stay hidden!
AB  - We report the case of a patient with severe muscular and articular tenderness
      that caused almost complete immobility. This subject had severe hypophosphatemia
      due to hyperphosphaturia. Fibroblast growth factor 23 (FGF-23) was abnormally
      high and the diagnostic of tumor-induced osteomalacia was made. Despite multiple
      tests, the tumor was not localized. In this report, we discuss different possible
      investigations to localize the tumor. Lastly, we review the potential therapy
      available when tumor is not found and can thus not be excised.

PMID- 21843523
TI  - Identification and modelling of a PPM protein phosphatase fold in the Legionella
      pneumophila deAMPylase SidD.
AB  - The intracellular parasitic bacterium Legionella pneumophila subverts host
      vesicle transport through reversible AMPylation of Rab1. The effector enzyme for
      deAMPylation is SidD. Here a complete PPM protein phosphatase fold catalytic
      domain in SidD is identified and modelled. The SidD model reveals insertions and
      deletions near the metal ion containing catalytic site which presumably determine
      its novel activity. It also sheds light on possible substrate binding residues
      and highlights the lack of an obvious group to act as general acid during
      reaction. Assignment of a PPM fold to SidD offers an important pointer towards
      identification of further deAMPylases.

PMID- 21843524
TI  - TR4 activates FATP1 gene expression to promote lipid accumulation in 3T3-L1
      adipocytes.
AB  - We show that TR4 facilitates lipid accumulation in 3T3-L1 adipocytes via
      induction of the FATP1 gene. Further study showed that TR4 transactivated FATP1
      5' promoter activity via direct binding to the TR4 responsive element located at
      the FATP1 5' promoter region. Constitutive overexpression of TR4 in 3T3-L1
      adipocytes resulted in increased lipid accumulation, accompanied by an increase
      in fatty acid uptake. However, small interfering RNA knockdown of FATP1 abolished
      TR4-enhanced fatty acid uptake. Moreover, microRNA-mediated silencing of TR4 in
      3T3-L1 adipocytes drastically reduced basal FATP1 5' promoter activity and FATP1
      expression with reduced lipid accumulation.

PMID- 21843525
TI  - Parents' testosterone and children's perception of parent-child relationship
      quality.
AB  - We examine the link between parental testosterone and children's perceptions of
      their relationship with their mother and father. Using data from 352
      predominantly white working and middle class families, we find no direct link
      between mother's and father's testosterone and parent-child closeness. However,
      the association between mothers' testosterone and mother-child closeness appears
      to be influenced by the quality of two other family relationships. When father's
      marital satisfaction is low, mothers with high testosterone have a poorer
      relationship with their children. And, when fathers report low levels of intimacy
      with their children, high testosterone women have a poorer relationship with
      their children. No comparable associations were observed among fathers.

PMID- 21843526
TI  - Comparative analysis of hemocyte phagocytosis between six species of arthropods
      as measured by flow cytometry.
AB  - Phagocytosis of pathogens by hemocytes is a rapid-acting immune response and
      represents a primary means of limiting microbial infection in some species of
      arthropods. To survey the relative capacity of hemocyte phagocytosis as a
      function of the arthropod immune response, we examined the extent of phagocytosis
      among a wide taxonomic range of arthropod species including a decapod crustacean
      (Litopenaeus vannamei), three ixodid tick species (Amblyomma americanum,
      Dermacentor variabilis, and Ixodes scapularis), a mosquito species (Aedes
      aegypti), and a larval moth (Manduca sexta). Injected fluorescent beads were used
      as a model to elicit phagocytosis and were measured by flow cytometry, a
      technique provided in detail that may be adapted for use with any species of
      arthropod. The data indicated that smaller arthropods generally had a higher
      proportion of phagocytic cells than larger arthropods.

PMID- 21843527
TI  - Nitric oxide synthase and cyclic GMP signaling in cardiac myocytes: from
      contractility to remodeling.
AB  - Cyclic guanosine 3'5'monophosphate (cGMP) is the common downstream second
      messenger of natriuretic peptides and nitric oxide. In cardiac myocytes, the
      physiological effects of cGMP are exerted through the activation of protein
      kinase G (PKG) signaling, and the activation and/or inhibition of
      phosphodiesterases (PDEs), providing an integration point between cAMP and cGMP
      signals. Specificity of cGMP signals is achieved through compartmentalization of
      cGMP synthesis by guanylate cyclases, and cGMP hydrolysis by PDEs. Increasing
      evidence suggests that cGMP-dependent signaling pathways play an important role
      in inhibiting cardiac remodeling, through the inhibition Ca(2+) handling upstream
      of pathological Ca(2+)-dependent signaling pathways. Thus, enhancing cardiac
      myocyte cGMP signaling represents a promising therapeutic target for treatment of
      cardiovascular disease. This article is part of a Special Issue entitled "Local
      Signaling in Myocytes."

PMID- 21843528
TI  - How ClpX unfolds GFP in stages by pulling.

PMID- 21843529
TI  - Who initiates proteasomal degradation?

PMID- 21843530
TI  - Cooperation and evolutionary dynamics in the public goods game with institutional
      incentives.
AB  - The one-shot public goods game is extended to include institutional incentives
      (i.e. reward and/or punishment) that are meant to promote cooperation. It is
      shown that the Nash equilibrium (NE) outcomes predict either partial or fully
      cooperative behavior in these extended multi-player games with a continuous
      strategy space. Furthermore, for some incentive schemes, multiple NE outcomes are
      shown to emerge. Stability of all these equilibria under standard evolutionary
      dynamics (i.e. the replicator equation and the canonical equation of adaptive
      dynamics) is characterized.

PMID- 21843531
TI  - Agmatine enhances neurogenesis by increasing ERK1/2 expression, and suppresses
      astrogenesis by decreasing BMP 2,4 and SMAD 1,5,8 expression in subventricular
      zone neural stem cells.
AB  - AIM: Our study aimed to demonstrate whether agmatine (Ag) could regulate
      proliferation and cell fate determination of subventricular zone neural stem
      cells (SVZ NSCs). MAIN METHODS: SVZ NSCs were grown in the presence of epidermal
      growth factor (EGF) and basic fibroblast growth factor (bFGF) (20ng/ml) until
      4days in vitro (DIV) and later the culture medium was replaced without EGF and
      bFGF until 11 DIV in the absence (EGF/bFGF(+/-)/Ag(-)) or presence of agmatine
      (EGF/bFGF(+/-)/Ag(+)). Another set SVZ NSCs were maintained with EGF and bFGF
      until 11 DIV without (EGF/bFGF(+/+)/Ag(-)) or with agmatine treatment
      (EGF/bFGF(+/+)/Ag(+)). Agmatine's effect on proliferation and cell death (H and
      PI staining and Caspase-3 immunostaining) was examined at DIV 4 and 11.
      Agmatine's (100MUM) effect on cell fate determination was confirmed by
      immunostaining and Western blot at 11 DIV. KEY FINDINGS: Agmatine treatment
      reduced the neurosphere size and total cell count number dose-dependently in all
      the experimental groups both at DIV 4 and11. Immunoblotting and staining results
      showed that agmatine increased the Tuj1 and Microtubule-associated protein 2
      (MAP2) and decreased the Glial fibrillary acidic protein (GFAP) with no change in
      the Oligo2 protein expressions. This neurogenesis effect of agmatine seems to
      have a relation with Extracellular-signal-regulated kinases (ERK1/2) activation
      and anti-astrogenesis effect is thought to be related with the suppression of
      Bone morphogenetic proteins (BMP) 2,4 and contraction of Sma and Mad (SMAD) 1,5,8
      protein expression. SIGNIFICANCE: This model could be an invaluable tool to study
      whether agmatine treated SVZ NSC transplantation to the central nervous system
      (CNS) injury could trigger neurogenesis and decrypt the full range of molecular
      events involved during neurogenesis in vivo as evidenced in vitro.

PMID- 21843532
TI  - Genistein, isoflavonoids in soybeans, prevents the formation of excess radiation
      induced centrosomes via p21 up-regulation.
AB  - The centrosome is a cytoplasmic organelle which duplicates once during each cell
      cycle, and the presence of excess centrosomes promote chromosome instability
      through chromosome missegregation following cytokinesis. Ionizing radiation (IR)
      can induce extra centrosomes by permitting the continuation of CDK2/Cyclin-A/E
      mediated centrosome duplication when cells are arrested in the cell cycle after
      irradiation. The work described here shows that, in addition to IR, extra
      centrosomes were induced in human U2OS and mouse NIH3T3 cells after treatment
      with agents which include DNA adduct-forming chemicals: benzopyrene (BP), 4
      nitroquinoline 1-oxide (4NQO), a DNA cross linker: cis-diamminedichloro-platinum
      (cisplatin), topoisomerase inhibitors: camptothecin, etoposide, genistein, and
      ultra-violet light (UV). These agents were divided into two categories with
      respect to the regulation of p21, which is an inhibitor of CDK2/Cyclin-A/E:
      specifically, p21 was up-regulated by an IR exposure and treatment with
      topoisomerase inhibitors. However, UV, BP, 4NQO and cisplatin down-regulated p21
      below basal levels. When cells were irradiated with IR in combination with all of
      these agents, except genistein, enhanced induction of extra centrosomes was
      observed, regardless of the nature of p21 expression. Genistein significantly
      suppressed the frequency of IR-induced extra centrosomes in a dose-dependent
      manner, and 20MUg/ml of genistein reduced this frequency to 66%. Consistent with
      this, genistein substantially up-regulated p21 expression over the induction
      caused by IR alone, while other agents down-regulated or marginally affected
      this. This suggests the inhibitory effect of genistein on the induction of extra
      centrosomes occurs through the inactivation of CDK2/Cyclin-A/E via p21 up
      regulation. This hypothesis is supported by the observation that p21 knockdown
      with siRNA reduced the activity of CDK2/Cyclin-A/E and restored the enhanced
      effect of a combined treatment with genistein and IR. These results demonstrate
      the preventive effect of genistein and a crucial role for p21 in IR-induced
      excess centrosomes.

PMID- 21843533
TI  - Mitochondrial DNA damage is sensitive to exogenous H(2)O(2) but independent of
      cellular ROS production in prostate cancer cells.
AB  - Intrinsic oxidative stress through enhanced production of reactive oxygen species
      (ROS) in prostate and other cancers may contribute to cancer progression due to
      its stimulating effect on cancer growth. In this study, we investigate
      differential responses to exogenous oxidative stimuli between aggressive prostate
      cancer and normal cell lines and explore potential mechanisms through
      interactions between cytotoxicity, cellular ROS production and oxidative DNA
      damage. The circular, multi-copy mitochondrial DNA (mtDNA) is used as a sensitive
      surrogate to oxidative DNA damage. We demonstrate that exogenous H(2)O(2) induces
      preferential cytotoxicity in aggressive prostate cancer than normal cells; a
      cascade production of cellular ROS, composed mainly of superoxide (O(2)(-)), is
      shown to be a critical determinant of H(2)O(2)-induced selective toxicity in
      cancer cells. In contrast, mtDNA damage and copy number depletion, as measured by
      a novel two-phase strategy of the supercoiling-sensitive qPCR method, are very
      sensitive to exogenous H(2)O(2) exposure in both cancer and normal cell lines.
      Moreover, we demonstrate for the first time that the sensitive mtDNA damage
      response to exogenous H(2)O(2) is independent of secondary cellular ROS
      production triggered by several ROS modulators regardless of cell phenotypes.
      These new findings suggest different mechanisms underpinning cytotoxicity and DNA
      damage induced by oxidative stress and a susceptible phenotype to oxidative
      injury associated with aggressive prostate cancer cells in vitro.

PMID- 21843534
TI  - Analysis of the common deletions in the mitochondrial DNA is a sensitive
      biomarker detecting direct and non-targeted cellular effects of low dose ionizing
      radiation.
AB  - One of the key issues of current radiation research is the biological effect of
      low doses. Unfortunately, low dose science is hampered by the unavailability of
      easily performable, reliable and sensitive quantitative biomarkers suitable
      detecting low frequency alterations in irradiated cells. We applied a
      quantitative real time polymerase chain reaction (qRT-PCR) based protocol
      detecting common deletions (CD) in the mitochondrial genome to assess direct and
      non-targeted effects of radiation in human fibroblasts. In directly irradiated
      (IR) cells CD increased with dose and was higher in radiosensitive cells.
      Investigating conditioned medium-mediated bystander effects we demonstrated that
      low and high (0.1 and 2Gy) doses induced similar levels of bystander responses
      and found individual differences in human fibroblasts. The bystander response was
      not related to the radiosensitivity of the cells. The importance of signal
      sending donor and signal receiving target cells was investigated by placing
      conditioned medium from a bystander response positive cell line (F11-hTERT) to
      bystander negative cells (S1-hTERT) and vice versa. The data indicated that
      signal sending cells are more important in the medium-mediated bystander effect
      than recipients. Finally, we followed long term effects in immortalized radiation
      sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR.
      In F11-hTERT cells CD level was increased until 35 days after IR then reduced
      back to control level by day 49. In S1-hTERT cells the increased CD level was
      also normalized by day 42, however a second wave of increased CD incidence
      appeared by day 49 which was maintained up to day 63 after IR. This second CD
      wave might be the indication of radiation-induced instability in the
      mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD
      in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation
      induced direct and non-targeted effects.

PMID- 21843535
TI  - Chromosomal aberrations in the bone marrow cells of mice induced by accelerated
      (12)C(6+) ions.
AB  - The whole bodies of 6-week-old male Kun-Ming mice were exposed to different doses
      of (12)C(6+) ions or X-rays. Chromosomal aberrations of the bone marrow (gaps,
      terminal deletions and breaks, fragments, inter-chromosomal fusions and sister
      chromatid union) were scored in metaphase 9h after exposure, corresponding to
      cells exposed in the G(2)-phase of the first mitosis cycle. Dose-response
      relationships for the frequency of chromosomal aberrations were plotted both by
      linear and linear-quadratic equations. The data showed that there was a dose
      related increase in the frequency of chromosomal aberrations in all treated
      groups compared to controls. Linear-quadratic equations were a good fit for both
      radiation types. The compound theory of dual radiation action was applied to
      decipher the bigger curvature (D(2)) of the dose-response curves of X-rays
      compared to those of (12)C(6+) ions. Different distributions of the five types of
      aberrations and different degrees of homogeneity were found between (12)C(6+) ion
      and X-ray irradiation and the possible underlying mechanism for these phenomena
      were analyzed according to the differences in the spatial energy deposition of
      both types of radiation.

PMID- 21843536
TI  - Translational models of schizophrenia.

PMID- 21843538
TI  - Neural correlates of the processing of self-referent emotional information in
      bulimia nervosa.
AB  - There is increasing interest in understanding the roles of distorted beliefs
      about the self, ostensibly unrelated to eating, weight and shape, in eating
      disorders (EDs), but little is known about their neural correlates. We therefore
      used functional magnetic resonance imaging to investigate the neural correlates
      of self-referent emotional processing in EDs. During the scan, unmedicated
      patients with bulimia nervosa (n=11) and healthy controls (n=16) responded to
      personality words previously found to be related to negative self beliefs in EDs
      and depression. Rating of the negative personality descriptors resulted in
      reduced activation in patients compared to controls in parietal, occipital and
      limbic areas including the amygdala. There was no evidence that reduced activity
      in patients was secondary to increased cognitive control. Different patterns of
      neural activation between patients and controls may be the result of either
      habituation to personally relevant negative self beliefs or of emotional blunting
      in patients.

PMID- 21843539
TI  - Where were those rabbits? A new paradigm to determine cerebral lateralisation of
      visuospatial memory function in children.
AB  - In the majority of people, functional differences are observed between the two
      cerebral hemispheres: language production is typically subserved by the left
      hemisphere and visuospatial skills by the right hemisphere. The development of
      this division of labour is not well understood and lateralisation of visuospatial
      function has received little attention in children. In this study we devised a
      child-friendly version of a paradigm to assess lateralisation of visuospatial
      memory using functional transcranial Doppler ultrasound (fTCD). In a group of 24
      adults we found this child-friendly version gave similar results to the original
      version of the task. In addition, fourteen children aged 6-8 years successfully
      completed the child-friendly fTCD task, showing a negative lateralisation index,
      indicating right hemispheric specialisation at the group level. Additionally, we
      assessed effects of task accuracy and reaction time on the lateralisation index.
      No effects were found, at the group level or at the level of single trials, in
      either the adult or the child group. We conclude that this new task reliably
      assesses lateralisation of visuospatial memory function in children as young as 6
      years of age, using fTCD. As such, it holds promise for investigating development
      of lateralisation of visuospatial function in typically and atypically developing
      children.

PMID- 21843540
TI  - Telling one face from another: electrocortical correlates of facial
      characteristics among individual female faces.
AB  - Research investigating the neural correlates of face processing has emphasized
      differences in neural activity when participants view faces versus other stimulus
      categories (e.g., houses). Much less is known about the neural mechanisms
      underlying the discrimination among individual faces. Using a large number of
      female faces, here we show that the amplitude of the face-sensitive N170
      electrocortical component is related to a range of facial characteristics. The
      right N170 amplitude was related to eye color and face width. The left N170
      amplitude was related to eye shape and face proportions, suggesting a functional
      dissociation between hemispheres. In contrast, the amplitude of the P100 and N250
      components was largely unaffected by these facial characteristics. Consistent
      with recent findings in non-human primates, we identify for the first time
      evidence of human electrocortical brain potentials that are sensitive to
      variations in specific facial characteristics, a prerequisite for recognizing the
      identity of individual faces.

PMID- 21843537
TI  - Modeling anxiety using adult zebrafish: a conceptual review.
AB  - Zebrafish (Danio rerio) are rapidly emerging as a useful animal model in
      neurobehavioral research. Mounting evidence shows the suitability of zebrafish to
      model various aspects of anxiety-related states. Here, we evaluate established
      and novel approaches to uncover the molecular substrates, genetic pathways and
      neural circuits of anxiety using adult zebrafish. Experimental approaches to
      modeling anxiety in zebrafish include novelty-based paradigms, pharmacological
      and genetic manipulations, as well as innovative video-tracking, 3D
      reconstructions, bioinformatics-based searchable databases and omics-based tools.
      Complementing traditional rodent models of anxiety, we provide a conceptual
      framework for the wider application of zebrafish and other aquatic models in
      anxiety research. This article is part of a Special Issue entitled 'Anxiety and
      Depression'.

PMID- 21843542
TI  - Resonance mechanism in empathic behavior BEES, BIS/BAS and psychophysiological
      contribution.
AB  - Empathy is related to the natural human ability to understand emotions and
      feelings of others, where a sort of "resonance" mechanism between the observer
      and the observed permits a direct form of understanding. The present study
      explored four different measures related to empathic behavior in a social
      context: autonomic behavior (skin conductance--SCR, and heart rate--HR), personal
      response to empathic scale (BEES), approach-withdrawal attitudes (BIS/BAS), and
      verbal self-report measures. Participants were presented with different
      interpersonal scene types (cooperation, non-cooperation, conflict, indifference),
      and they were required to empathize with them. Different autonomic response
      patterns were found as a function of the interpersonal situations: SCR and HR
      increased in case of conflictual and non-cooperative situations. This result was
      confirmed by self-rating measures on empathy, since emotional involvement and
      valence attributed to the scenes varied in concomitance with psychophysiological
      parameters. Third, high and low BEES subjects showed different empathic behavior:
      high empathic subjects were more responsive (on both self-report and autonomic
      response) to empathy-related situations than low empathic subjects. Finally, BIS
      and BAS attitudes demonstrated a significant relationship with both BEES and
      autonomic patterns: high BAS subjects were more responsive and empathic with
      positive, cooperative situations, whereas high BIS empathized with more negative,
      conflictual situations. The convergence of these multidimensional measures was
      discussed.

PMID- 21843541
TI  - Fos expression following regimens of predator stress versus footshock that
      differentially affect prepulse inhibition in rats.
AB  - Stress is suggested to exacerbate symptoms and contribute to relapse in patients
      with schizophrenia and several other psychiatric disorders. A prominent feature
      of many of these illnesses is an impaired ability to filter information through
      sensorimotor gating processes. Prepulse inhibition (PPI) is a functional measure
      of sensorimotor gating, and known to be deficient in schizophrenia and sometimes
      in post-traumatic stress disorder (PTSD), both of which are also sensitive to
      stress-induced symptom deterioration. We previously found that a psychological
      stressor (exposure to a ferret without physical contact), but not footshock,
      disrupted PPI in rats, suggesting that intense psychological stress/trauma may
      uniquely model stress-induced sensorimotor gating abnormalities. In the present
      experiment, we sought to recreate the conditions where we found this behavioral
      difference, and to explore possible underlying neural substrates. Rats were
      exposed acutely to ferret stress, footshock, or no stress (control). 90 min
      later, tissue was obtained for Fos immunohistochemistry to assess neuronal
      activation. Several brain regions (prelimbic, infralimbic, and cingulate
      cortices, the paraventricular hypothalamic nucleus, the paraventricular thalamic
      nucleus, and the lateral periaqueductal gray) were equally activated following
      exposure to either stressor. Interestingly, the medial amygdala and dorsomedial
      periaqueductal gray had nearly twice as much Fos activation in the ferret-exposed
      rats as in the footshock-exposed rats, suggesting that higher activation within
      these structures may contribute to the unique behavioral effects induced by
      predator stress. These results may have implications for understanding the neural
      substrates that could participate in sensorimotor gating abnormalities seen in
      several psychiatric disorders after psychogenic stress.

PMID- 21843543
TI  - Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal
      death by chronic coenzyme Q10 pretreatment.
AB  - Numerous epidemiological studies have shown an association between pesticide
      exposure and increased risk of developing Parkinson's diseases. Oxidative stress
      generated as a result of mitochondrial dysfunction has been implicated as an
      important factor in the etiology of Parkinson's disease. Previously, we reported
      that chronic dichlorvos exposure causes mitochondrial impairments and
      nigrostriatal neuronal death in rats. The present study was designed to test
      whether Coenzyme Q(10) (CoQ(10)) administration has any neuroprotective effect
      against dichlorvos mediated nigrostriatal neuronal death, alpha-synuclein
      aggregation, and motor dysfunction. Male albino rats were administered dichlorvos
      by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12
      weeks. Results obtained there after showed that dichlorvos exposure leads to
      enhanced mitochondrial ROS production, alpha-synuclein aggregation, decreased
      dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration.
      Pretreatment by Coenzyme Q(10) (4.5 mg/kg ip for 12 weeks) to dichlorvos treated
      animals significantly attenuated the extent of nigrostriatal neuronal damage, in
      terms of decreased ROS production, increased dopamine and its metabolite levels,
      and restoration of motor dysfunction when compared to dichlorvos treated animals.
      Thus, the present study shows that Coenzyme Q(10) administration may attenuate
      dichlorvos induced nigrostriatal neurodegeneration, alpha-synuclein aggregation
      and motor dysfunction by virtue of its antioxidant action.

PMID- 21843544
TI  - Contrasting the processes of texture segmentation and discrimination with static
      and phase-reversing stimuli.
AB  - Regions of visual texture can be automatically segregated from one another when
      they abut but also discriminated from one another if they are separated in space
      or time. A difference in mean orientation between two textures serves to
      facilitate their segmentation, whereas a difference in orientation variance does
      not. The present study further supports this notion, by replicating the findings
      of Wolfson and Landy (1998) in showing that judgments (odd-one-out) made for
      textures that differ in mean orientation were more accurate (and more rapid) when
      the textures were abutting than when separated, whereas judgments of variance
      were made no more accurately for abutting relative to separated textures.
      Interestingly, however, responses were overall faster for textures differing in
      variance when they were separated compared to when they were abutting. This is
      perhaps due to the clear separation boundary, which serves to delineate the
      regions on which to perform some regional estimation of orientation variance. A
      second experiment highlights the phase-insensitivity of texture segmentation, in
      that locating a texture edge (defined by a difference in mean orientation) in
      high frequency orientation-reversing stimuli can be performed at much higher
      frequencies than the discrimination of the same regions but with the texture
      contour masked. Textures that differed in variance did not exhibit this effect. A
      final experiment demonstrates that the phase-insensitive perception of texture
      borders improves with eccentric viewing relative to the fovea, whereas perception
      of the texture regions does not. Together, these experiments show dissociations
      between edge- and region-based texture analysis mechanisms and suggest a fast,
      sign-invariant contour extraction system mediating texture segmentation, which
      may be closely linked to the magnocellular subdivision of visual processing.

PMID- 21843545
TI  - Analyzing electrical activities of pancreatic beta cells using mathematical
      models.
AB  - Bursts of repetitive action potentials are closely related to the regulation of
      glucose-induced insulin secretion in pancreatic beta cells. Mathematical studies
      with simple beta-cell models have established the central principle that the
      burst-interburst events are generated by the interaction between fast membrane
      excitation and slow cytosolic components. Recently, a number of detailed models
      have been developed to simulate more realistic beta cell activity based on
      expanded findings on biophysical characteristics of cellular components. However,
      their complex structures hinder our intuitive understanding of the underlying
      mechanisms, and it is becoming more difficult to dissect the role of a specific
      component out of the complex network. We have recently developed a new detailed
      model by incorporating most of ion channels and transporters recorded
      experimentally (the Cha-Noma model), yet the model satisfies the charge
      conservation law and reversible responses to physiological stimuli. Here, we
      review the mechanisms underlying bursting activity by applying mathematical
      analysis tools to representative simple and detailed models. These analyses
      include time-based simulation, bifurcation analysis and lead potential analysis.
      In addition, we introduce a new steady-state I-V (ssI-V) curve analysis. We also
      discuss differences in electrical signals recorded from isolated single cells or
      from cells maintaining electrical connections within multi-cell preparations.
      Towards this end, we perform simulations with our detailed pancreatic beta-cell
      model.

PMID- 21843546
TI  - Chronic agomelatine and fluoxetine induce antidepressant-like effects in H/Rouen
      mice, a genetic mouse model of depression.
AB  - The novel antidepressant agomelatine behaves as an agonist at melatonergic MT(1)
      and MT(2) receptors and as an antagonist at serotonin 5-HT(2C) receptors. This
      study investigated the effects of agomelatine and fluoxetine in a genetic model
      of depression called H/Rouen mice Male and female H/Rouen (helpless line) and
      NH/Rouen (nonhelpless line) mice, received once daily for 3 weeks agomelatine (10
      and 50 mg/kgi.p.), fluoxetine (10 mg/kgi.p.) or vehicle. Immobility duration in
      the tail suspension test (TST) was assessed on day 1 (D1), day 8 (D8), day 15
      (D15) and day 22 (D22). Locomotor activity in a novel environment was assessed on
      day 18 (D18) and anhedonia (2-bottle sucrose preference test) was considered
      after the end of chronic treatment, from days 22 to 25. Agomelatine (50 mg/kg)
      significantly reduced immobility at D15 (p<0.01), and D22 (p<0.001) in treated
      H/Rouen mice whereas agomelatine at 10 mg/kg did not induce a statistically
      significant change. Fluoxetine reduced immobility at D8 (p<0.01), D15 (p<0.001)
      and D22 (p<0.001). Locomotor activity was unchanged in all treated groups as
      compared to vehicle groups. In the sucrose test, there was a significant decrease
      in sucrose preference in H/Rouen mice compared with NH/Rouen mice receiving
      vehicle. Both agomelatine doses (10 mg/kg (p=0.05) and 50 mg/kg (p<0.001) as well
      as fluoxetine (p<0.001) significantly increased the sucrose preference in H/Rouen
      mice as compared with H/Rouen mice that had received vehicle. These data indicate
      that the novel antidepressant agomelatine has antidepressant-like properties in
      H/Rouen mice, a genetic model of depression.

PMID- 21843547
TI  - The epistemological function of Hill's criteria.
AB  - OBJECTIVE: This article outlines an epistemological framework for understanding
      how Hill's criteria may aid us in establishing a causal hypothesis (A causes B)
      in an observational study. METHOD: We consider Hill's criteria in turn with
      respect to their ability or otherwise to exclude alternative hypotheses (B causes
      A; there is a common cause of A and B; there is no causal connection between A
      and B). RESULTS: We may classify Hill's criteria according to which of the
      alternative hypotheses they are able to exclude, and also on the basis of whether
      they relate to (a) evidence from within observational study or (b) evidence
      independent of that study. It is noted that no criterion is able to exclude the
      common cause hypothesis in a systematic way. CONCLUSION: Observational studies
      are typically weaker than experimental studies, since the latter can
      systematically exclude competing hypotheses, whereas observational studies lack a
      systematic way of ruling out the common cause hypothesis.

PMID- 21843548
TI  - Relationships between hours of sleep and health-risk behaviors in US adolescent
      students.
AB  - OBJECTIVE: To examine associations between insufficient sleep (<8h on average
      school nights) and health-risk behaviors. METHODS: 2007 national Youth Risk
      Behavior Survey data of U.S. high school students (n=12,154) were analyzed.
      Associations were examined on weighted data using multivariate logistic
      regression. RESULTS: Insufficient sleep on an average school night was reported
      by 68.9% of students. Insufficient sleep was associated with higher odds of
      current use of cigarettes (age-adjusted odds ratio [AOR], 1.67; 95% confidence
      interval [CI], 1.45-1.93), marijuana (AOR, 1.52; 95% CI, 1.31-1.76), and alcohol
      (AOR, 1.64; 95% CI, 1.46-1.84); current sexual activity (AOR, 1.41; 95% CI, 1.25
      1.59); seriously considered attempting suicide (AOR, 1.86; 95% CI, 1.60-2.16);
      feeling sad or hopeless (AOR, 1.62; 95% CI, 1.43-1.84); physical fighting (AOR,
      1.40; 95% CI, 1.24-1.60), not being physically active at least 60min >= 5days in
      the past 7days (AOR, 1.16; 95% CI, 1.04-1.29), using the computer >=3h/day (AOR,
      1.58; 95% CI, 1.38-1.80), and drinking soda/pop > 1time/day (AOR, 1.14; 95% CI,
      1.03-1.28). CONCLUSION: Two-thirds of adolescent students reported insufficient
      sleep, which was associated with many health-risk behaviors. Greater awareness of
      the impact of sleep insufficiency is vital.

PMID- 21843549
TI  - Comparative genomics and phylogeny of the IncI1 plasmids: a common plasmid type
      among porcine enterotoxigenic Escherichia coli.
AB  - Increasing reports of multidrug resistance conferred by conjugative plasmids of
      Enterobacteriaceae necessitate a better understanding of their evolution. One
      such group is the narrow-host-range IncI1 plasmid type, known for their ability
      to carry genes encoding resistance to extended-spectrum beta lactamases. The
      focus of this study was to perform comparative sequencing of IncI1 plasmids from
      porcine enterotoxigenic Escherichia coli (ETEC), isolated irrespective of
      antimicrobial susceptibility phenotype. Five IncI1 plasmids of porcine ETEC
      origin and one IncI1 plasmid from a Salmonella enterica serovar Kentucky isolate
      from a healthy broiler chicken were sequenced and compared to existing IncI1
      plasmid sequences in an effort to better understand the overall genetic
      composition of the IncI1 plasmid lineages. Overall, the sequenced porcine ETEC
      IncI1 plasmids were divergent from other sequenced IncI1 plasmids based upon
      multiple means of inferred phylogeny. High occurrences of IncI1 and IncA/C
      plasmid-associated genes and the blaTEM and blaCMY-2 beta lactamase genes were
      observed among porcine ETEC. However, the presence of blaTEM and blaCMY-2 did not
      strongly correlate with IncI1 plasmid possession, suggesting that these plasmids
      in porcine ETEC are not primarily associated with the carriage of such resistance
      genes. Overall, this work suggests a conservation of the IncI1 plasmid backbone
      among sequenced plasmids with a single locus for the acquisition of accessory
      genes, such as those associated with antimicrobial resistance. Furthermore, the
      high occurrence of IncI1 and IncA/C plasmids among clinical E. coli from
      commercial swine facilities is indicative of extensive horizontal gene transfer
      among porcine ETEC.

PMID- 21843550
TI  - Multimodal vessel mapping for precise large area alignment of functional optical
      imaging data to neuroanatomical preparations in marmosets.
AB  - Imaging technologies, such as intrinsic optical imaging (IOI), functional
      magnetic resonance imaging (fMRI) or multiphoton microscopy provide excellent
      opportunities to study the relationship between functional signals recorded from
      a cortical area and the underlying anatomical structure. This, in turn, requires
      accurate alignment of the recorded functional imaging data with histological
      datasets from the imaged tissue obtained after the functional experiment. This
      alignment is complicated by distortions of the tissue which naturally occur
      during histological treatment, and is particularly difficult to achieve over
      large cortical areas, such as primate visual areas. We present here a method that
      uses IOI vessel maps revealed in the time course of the intrinsic signal, in
      combination with vascular casts and vascular lumen labeling techniques together
      with a pseudo three dimensional (p3D) reconstruction of the tissue architecture
      in order to facilitate alignment of IOI data with posthoc histological datasets.
      We demonstrate that by such a multimodal vessel mapping approach, we are able to
      constitute a hook in anatomical-functional data alignment that enables the
      accurate assignment of functional signals over large cortical regions. As an
      example, we present precise alignments of IOI responses showing orientation
      selectivity of primate V1 with anatomical sections stained for cytochrome-oxidase
      reactivity.

PMID- 21843551
TI  - Development of mechanical and thermal nociceptive threshold testing devices in
      unrestrained birds (broiler chickens).
AB  - Behavioural signs of pain are difficult to quantify and interpret in animals.
      Nociceptive threshold testing is therefore a useful method for examining the
      perception and processing of noxious stimuli underlying pain states. Devices were
      developed to measure response thresholds to quantified, ramped mechanical and
      thermal nociceptive stimuli applied to the leg or keel of unrestrained birds. Up
      to 9N mechanical force was delivered via a single round-ended 2mm pin using a
      pneumatic actuator at 0.4Ns(-1). Heat was applied through a small copper element
      at 0.8 degrees Cs(-1) to a maximum of 50 degrees C. The repeatability and
      reliability of threshold measures were validated using 10-12 broiler chickens
      (aged 49-66 days) per site and modality. Mechanical threshold, or skin and
      threshold temperature, were recorded over three sessions across a 36h period.
      Both stimulus types elicited clear, reproducible behavioural responses.
      Mechanical threshold means and 95% confidence intervals were 3.0 (2.8-3.2)N for
      keel and 2.0 (1.8-2.1)N for leg sites. Keel thermal tests gave a mean skin
      temperature of 39.3 (39.1-39.5) degrees C, and threshold of 46.8 (46.6-47.1)
      degrees C. Leg skin temperature was 35.7 (35.6-35.9) degrees C and threshold 42.5
      (42.2-42.8) degrees C. Threshold measures were consistent within and across
      sessions and birds showed individual repeatability across tests within sessions.
      Individual birds' mechanical keel thresholds were also repeatable across
      sessions. The apparatus gave reliable, reproducible measurements of thresholds to
      noxious mechanical and thermal stimuli. The range recorded was comparable with
      previously published nociceptor thresholds in dissected chicken nerve filament
      fibres, and the method appears suitable for studying nociceptive processes in
      broiler chickens.

PMID- 21843552
TI  - Critical studies on binding-based RT-PCR detection of infectious Noroviruses.
AB  - Attempts were made to discriminate between infectious and non-infectious
      Noroviruses (NoVs) based on their viral binding properties followed by reverse
      transcription polymerase chain reaction (RT-PCR). Murine norovirus-1 (MNV-1) was
      employed as a surrogate to test the principle. Detection of both infectious and
      inactivated MNV-1 was investigated by the plaque assay, RT-PCR and binding-based
      RT-PCRs. The cell line RAW 264.7 and the ganglioside GD1a were used as binding
      receptors respectively in combination with RT-PCR. In the second stage of
      testing, similar approaches were applied to the two main genogroups of human NoVs
      (GI and GII). Differentiated Caco-2 cells and pig gastric mucin were tested as
      the binding receptors. Bovine serum albumin (BSA) was used as a non-specific
      binding control. In this study, the binding-based RT-PCRs decreased the detection
      of non-infectious NoVs by 1-3-log(10) while all infectious viral particles were
      detected. No significant difference was observed between the binding-based RT
      PCRs within the concentration range investigated, except the binding level of
      human NoVs GII to pig gastric mucin was higher than to differentiated Caco-2
      cells and BSA. This study indicates an improvement in the evaluation of the
      infectivity of non-cultivable human NoVs. This is also a comprehensive study on
      both specific and non-specific binding properties of NoVs.

PMID- 21843553
TI  - Validation of an internally controlled one-step real-time multiplex RT-PCR assay
      for the detection and quantitation of dengue virus RNA in plasma.
AB  - Dengue is mosquito-borne virus infection that annually causes ~50 million
      clinically apparent cases worldwide. An internally controlled one-step real-time
      multiplex RT-PCR assay was developed for detection and quantitation of DENV RNA
      in plasma sample by using specific primers and fluorogenic TaqMan probes. All
      primers and probes targeted sequences near the 3' end of the NS5 gene. The method
      comprised two multiplex assays and was validated for sensitivity, specificity,
      linearity, reproducibility and precision. An internal control template was spiked
      into each clinical specimen to provide quality assurance for each experimental
      step. The assay allowed for detection of between 0.5 and 3 infectious particles
      per mL, is rapid and has been operationally characterized in 287 Vietnamese
      dengue patients from two therapeutic intervention trials at the Hospital for
      Tropical Diseases, Ho Chi Minh City, Viet Nam.

PMID- 21843554
TI  - The unique antiviral activity of artesunate is broadly effective against human
      cytomegaloviruses including therapy-resistant mutants.
AB  - Current therapy options to treat infections with human cytomegalovirus face
      severe limitations leading to a continued search for novel drug candidates. Here,
      we describe novel characteristics of the strong antiviral potency of the drug
      artesunate. In vitro virus replication systems were applied to analyze a number
      of laboratory and clinically relevant strains of human cytomegalovirus. An
      inhibitory block at a very early stage of infection was demonstrated. Time-of
      addition experiments indicated that the antiviral efficacy could be optimized
      when artesunate was applied as fractional doses consecutively added post
      infection. Artesunate showed a clearly higher anti-cytomegaloviral activity than
      its parental drug artemisinin (approximately 10-fold) or other artesunate-related
      compounds. Mean IC(50) values of artesunate for a variety of standard therapy
      resistant virus mutants were within a 2-fold range compared to wild-type virus.
      Furthermore, a synergistic effect was identified when artesunate was combined
      with the mechanistically distinct antiviral compound maribavir. These findings
      point to unique antiviral properties of artesunate which may offer an advantage
      over standard antiviral therapy particularly in cases of drug resistance.

PMID- 21843555
TI  - Seizure-induced structural and functional changes in the rat hippocampal
      formation: comparison between brief seizures and status epilepticus.
AB  - Prolonged seizures produce death of hippocampal neurons, which is thought to
      initiate epileptogenesis and cause a disruption of hippocampally mediated
      behaviors. This study aimed to evaluate behavioral and neuroanatomical changes
      induced by brief seizures and to compare them with changes induced by prolonged
      seizures. Adult rats were administered 6 brief seizures, elicited by electroshock
      (ECS). Prolonged seizures (status epilepticus, SE) were induced by pilocarpine.
      Two months later, the rats' behavior was tested using the Morris water maze,
      passive avoidance and active avoidance tests. The number of neurons in the
      hippocampal formation was estimated using stereological methods. ECS seizures
      produced loss of neurons, ranging between 14% and 26%, in the dentate hilus,
      subiculum, presubiculum, parasubiculum, and entorhinal layers III and V/VI.
      However, the neuron loss caused by SE in the same structures, as well as in the
      hippocampal CA3 and CA1 fields, ranged between 34% and 50%. SE additionally
      killed many neurons in the dentate granular layer, postsubiculum and entorhinal
      layer II. ECS treatment caused mild impairments in spatial learning and passive
      avoidance, but it was not associated with spontaneous motor seizures. In
      contrast, SE produced a severe disruption of spatial learning, passive and active
      avoidance, and led to the development of spontaneous seizures. These data show
      that both prolonged seizure activity and brief seizures result in structural and
      functional alterations in the temporal lobe circuits, but those caused by
      prolonged seizures are considerably more severe. Hippocampal damage elicited by
      brief seizures does not necessarily lead to spontaneous motor seizures.

PMID- 21843556
TI  - A reverse translational approach to quantify approach-avoidance conflict in
      humans.
AB  - Animal approach-avoidance conflict paradigms have been used extensively to
      characterize effects of anxiolytic agents and probe neural circuitry related to
      anxiety. However, there are few behavioral approaches to measure conflict in
      human populations, limiting the translation of findings from animal conflict
      tasks to human clinical research. We developed a novel approach-avoidance
      conflict (AAC) paradigm involving situations in which the same decision is
      associated with "reward" (points) and "punishment" (negative affective stimuli).
      The AAC task was completed by 95 young adults (56 female) with varying levels of
      self-reported trait anxiety. As expected, conflict-related approach behavior
      correlated with self-reported motivation to approach reward and avoid punishment
      and greater reward level increased approach behavior. Additionally, females
      exhibited less approach behavior than males. Anxiety Sensitivity Index (Physical
      subscale) scores related negatively to approach behavior for males, while
      Behavioral Activation Scale (BAS, Fun Seeking subscale) scores related positively
      to approach behavior for females. Results support the utility of the AAC task as
      a behavioral test that has strong reverse translational features. Findings
      indicate that approach drives and anxiety sensitivity may be important in
      determining conflict behavior for females and males respectively. The approach
      avoidance conflict task offers a novel, translational measure to probe neural
      systems underlying conflict behavior, motivational processes, and anxiety
      disorders.

PMID- 21843557
TI  - Newborn neurons in the adult olfactory bulb: unique properties for specific odor
      behavior.
AB  - The generation of new cells in the adult brain reveals a new form of plasticity
      in the neuronal network. New cells are constantly migrating to and integrating
      into the pre-existing neuronal network in the olfactory bulb. The exact role of
      new neurons in the adult olfactory bulb and in odor behavior remains elusive
      despite continuous progress. The unique properties of these adult-born
      interneurons that distinguish them from pre-existing bulbar neurons allow them to
      adapt the processing of odor information in the neuronal network of the olfactory
      bulb in response to sensory experience. The combination of diverse methods for
      modulating neurogenesis levels with distinct behavioral paradigms has revealed
      that interneurons generated during adulthood play a role in olfactory behavior.
      In this review we provide an overview of the unique properties of adult-born
      neurons that integrate into the olfactory bulb as well as their role in odor
      behavior.

PMID- 21843559
TI  - Effects of sleep deprivation on auditory change detection: a N1-mismatch
      negativity study.
AB  - The effects of sleep deprivation on neural activity underlying stimulus change
      detection are still debated. The aim of this study was to investigate the effects
      of sleep deprivation on the relationship between N1 refractoriness and Mismatch
      Negativity (MMN) as indexes of different stages of change detection.
      Respectively, N1 represents the sensory feature trace creation with stimulus
      repetition and MMN represents the memory-based detection of deviance in a new
      incoming stimulus. Event-related potentials (ERPs) were recorded from 22 healthy
      participants during a passive auditory oddball task after a night of normal sleep
      and after a night of total sleep deprivation (TSD). Importantly, stimulus
      presentation was organized as a train of 10 stimuli, so that N1 refractoriness
      could be measured as amplitude decrease with stimulus repetition within each
      train. Results showed that N1 refractoriness and MMN were not affected by TSD
      suggesting that the change detection process was preserved in our paradigm.
      However, the overall N1 amplitude increased after TSD, an effect that may be
      related to an enhancement of cortical excitability.

PMID- 21843560
TI  - RNA viruses and their silencing suppressors boost Abutilon mosaic virus, but not
      the Old World Tomato yellow leaf curl Sardinia virus.
AB  - Mixed viral infections can induce different changes in symptom development,
      genome accumulation and tissue tropism. These issues were investigated for two
      phloem-limited begomoviruses, Abutilon mosaic virus (AbMV) and Tomato yellow leaf
      curl Sardinia virus (TYLCSV) in Nicotiana benthamiana plants doubly infected by
      either the potyvirus Cowpea aphid-borne mosaic virus (CABMV) or the tombusvirus
      Artichoke mottled crinkle virus (AMCV). Both RNA viruses induced an increase of
      the amount of AbMV, led to its occasional egress from the phloem and induced
      symptom aggravation, while the amount and tissue tropism of TYLCSV were almost
      unaffected. In transgenic plants expressing the silencing suppressors of CABMV
      (HC-Pro) or AMCV (P19), AbMV was supported to a much lesser extent than in the
      mixed infections, with the effect of CABMV HC-Pro being superior to that of AMCV
      P19. Neither of the silencing suppressors influenced TYLCSV accumulation. These
      results demonstrate that begomoviruses differentially respond to the invasion of
      other viruses and to silencing suppression.

PMID- 21843558
TI  - The elusive middle domain of Hsp104 and ClpB: location and function.
AB  - Hsp104 in yeast and ClpB in bacteria are homologous, hexameric AAA+ proteins and
      Hsp100 chaperones, which function in the stress response as ring-translocases
      that drive protein disaggregation and reactivation. Both Hsp104 and ClpB contain
      a distinctive coiled-coil middle domain (MD) inserted in the first AAA+ domain,
      which distinguishes them from other AAA+ proteins and Hsp100 family members.
      Here, we focus on recent developments concerning the location and function of the
      MD in these hexameric molecular machines, which remains an outstanding question.
      While the atomic structure of the hexameric assembly of Hsp104 and ClpB remains
      uncertain, recent advances have illuminated that the MD is critical for the
      intrinsic disaggregase activity of the hexamer and mediates key functional
      interactions with the Hsp70 chaperone system (Hsp70 and Hsp40) that empower
      protein disaggregation.

PMID- 21843561
TI  - Effect of integrin targeting and PEG shielding on polyplex micelle
      internalization studied by live-cell imaging.
AB  - alpha(v)beta(3) and alpha(v)beta(5) integrins are attractive target structures
      for cancer therapy as they are upregulated in tumor and tumor associated host
      cells and play a pivotal role for tumor growth and metastasis. Gene vectors such
      as polyplex micelles consisting of thiolated PEG-block-poly(lysine) copolymers
      complexed with plasmid DNA can be targeted to these specific integrins by
      equipment with a cyclic RGD peptide. In this study, we analyzed the effect of the
      RGD ligand on micelle endocytosis by comparing fluorescently labeled, targeted
      and untargeted micelles in live-cell imaging experiments with highly sensitive
      fluorescence microscopy and flow cytometry. Two micelle types with 12 kDa (PEG12)
      and 17 kDa (PEG17) PEG shell layers were examined to evaluate the influence of
      surface shielding on the internalization characteristics. Our results reveal
      three major effects: First, the RGD ligand accelerates the internalization of
      micelles into integrin expressing HeLa cells without changing the uptake pathway
      of the micelles. Both targeted as well as untargeted micelles are predominantly
      internalized via clathrin mediated endocytosis. Second, the PEG shielding of
      micelles has an important effect on their targeting specificity. At high PEG
      shielding selective endocytosis of integrin targeted micelles occurs, whereas at
      low PEG shielding targeted and untargeted micelles show comparable
      internalization. In addition, PEG17 RGD(+) micelles induce the highest reporter
      gene expression. Third, our data demonstrate a clear influence of the applied
      micelle dose on the internalization of integrin targeted micelles. We propose
      that PEG17 shielded micelles equipped with a cyclic RGD ligand are the favored
      system of choice for clinical therapy as they exhibit higher transgene
      expression, a higher specificity for integrin-dependent endocytosis compared to
      PEG12 shielded micelles, and are functional at low doses as well.

PMID- 21843562
TI  - A strategy to deliver genes to cystic fibrosis lungs: a battle with environment.
AB  - Cystic fibrosis (CF) sputum, a tenacious biopolymer network accumulating in the
      airways, critically interferes with the effectiveness of pulmonary gene delivery.
      To overcome this challenge, nanoparticulate ternary gene-polymer complexes were
      encapsulated in inhalable dry microparticles containing mannitol. When applied on
      a layer of artificial sputum, which comprised major components of CF sputum such
      as DNA and mucin, mannitol microparticles rapidly dissolved in it and enhanced
      transport of nanoparticles across the sputum layer. Despite the improvement of
      nanoparticle transport in the artificial sputum, the gene-polymer complex passing
      the sputum did not show gene transfection because of the significant inactivation
      by DNA and, to a lesser extent, mucin. Particle size measurement suggested that
      aggregation of the gene transfer agents was mainly responsible for the activity
      loss. These results indicate that the delivery of gene transfer agent across CF
      sputum depended not only on the ability to penetrate the sputum but also on
      preservation of the activity during and/or after the transport.

PMID- 21843563
TI  - Coiled-coil based drug-free macromolecular therapeutics: in vivo efficacy.
AB  - We evaluated a new concept in cancer therapy, coiled-coil mediated induction of
      apoptosis in Raji B cells, for treatment of human B-cell lymphoma in a
      preclinical animal model. The system is composed of a pair of complementary
      coiled-coil peptides, CCE and CCK, forming antiparallel heterodimers; Fab'
      fragment of the 1F5 anti-CD20 antibody; and N-(2-hydroxypropyl)methacrylamide
      (HPMA) copolymer. One peptide is conjugated to the Fab' fragment (Fab'-CCE), the
      other is conjugated in multiple grafts to polyHPMA (CCK-P; P is the HPMA
      copolymer backbone). Intravenous administration of Fab'-CCE conjugate, followed
      by the administration of CCK-P produced long-term survivors in SCID (C.B.-17)
      mice bearing human B-lymphoma xenografts. The rationale of the design is the
      absence of low molecular weight drugs and the fact that crosslinking of CD20 at B
      cell surface results in apoptosis. This approach creates a new paradigm for
      manipulating molecular recognition principles in the design of improved cancer
      treatment.

PMID- 21843564
TI  - Evaluation of amorphous solid dispersion properties using thermal analysis
      techniques.
AB  - Amorphous solid dispersions are an increasingly important formulation approach to
      improve the dissolution rate and apparent solubility of poorly water soluble
      compounds. Due to their complex physicochemical properties, there is a need for
      multi-faceted analytical methods to enable comprehensive characterization, and
      thermal techniques are widely employed for this purpose. Key parameters of
      interest that can influence product performance include the glass transition
      temperature (T(g)), molecular mobility of the drug, miscibility between the drug
      and excipients, and the rate and extent of drug crystallization. It is important
      to evaluate the type of information pertaining to the aforementioned properties
      that can be extracted from thermal analytical measurements, in addition to
      considering any inherent assumptions or limitations of the various analytical
      approaches. Although differential scanning calorimetry (DSC) is the most widely
      used thermal analytical technique applied to the characterization of amorphous
      solid dispersions, there are many established and emerging techniques which have
      been shown to provide useful information. Comprehensive characterization of
      fundamental material descriptors will ultimately lead to the formulation of more
      robust solid dispersion products.

PMID- 21843565
TI  - Treatment of atherogenic liver based on the pathogenesis of nonalcoholic fatty
      liver disease: a novel approach to reduce cardiovascular risk?
AB  - Nonalcoholic fatty liver disease (NAFLD), which spans a spectrum of conditions
      ranging from simple steatosis to progressive nonalcoholic steatohepatitis (NASH),
      is the most common chronic liver disease and a relevant public health issue. The
      prevalence of NAFLD depends on adiposity, age, gender and ethnicity. The natural
      history of liver disease in those with NAFLD critically depends on liver
      histological changes. However, cardiovascular mortality is increased in NAFLD,
      particularly in middle-aged adults. Against such a background, this review
      consists of three sections. First, data on NAFLD as a novel mechanism of
      increased cardiovascular risk via hyperinsulinism, pro-thrombotic potential, and
      subclinical inflammation are summarized. Next, the role of atherogenic liver in
      the development of manifestations of oxidative stress and atherosclerosis is
      emphasized. Finally, whether and how treating NAFLD will mechanistically result
      in reduced cardiovascular risk through ameliorated metabolic syndrome is
      discussed.

PMID- 21843566
TI  - Expression of toll-like receptor TLR-2, TLR-3, TLR-4 and TLR-9 is increased in
      placentas from patients with preeclampsia.
AB  - BACKGROUND AND AIMS: Few studies have examined the presence of Toll-like
      receptors (TLRs) in term placentas from women with preeclampsia, such, have
      focused on TLR-4 and TLR-2 analysis. Whereas an increase in TLR-4 immunostaining
      has been observed in preeclampsia, it is even higher in placentas with
      chorioamnionitis compared with normal pregnancy. Expression of TLR-2 has not been
      associated with preeclampsia. The relationship of TLR-3 and TLR-9, which may
      recognize dsRNA or DNA, either derived either from microorganisms or from
      apoptotic cells and thus may be involved with this pathology, has not been
      studied in term placentas. We undertook this study to determine if there are
      changes in the expression and localization of TLR-2, TLR-4, TLR-3 and TLR-9 in
      preeclamptic term placentas as compared with normal placentas. METHODS: A
      prospective, cross-sectional and comparative study was done in a group of ten
      patients with 38-40 gestation weeks, both in preeclamptic and control cases.
      Immunofluorescence detection of TLRs was performed in samples of placenta and
      analyzed by confocal microscopy. RESULTS: It was observed that TLR-2, TLR-3, TLR
      4 and TLR-9 were expressed both in normal and preeclamptic placentas, in the
      trophoblast, at the vascular endothelium (where TLR-2 and TLR-9 staining was
      pronounced), and at placental villous stroma, although increased expression was
      detected in preeclampsia. In addition, co-localization of TLR-2 and TLR-4 as well
      as of TLR-3 and TL9 was found in the trophoblast. CONCLUSIONS: TLR-2, -3, -4 and 
      9 expressions are increased in preeclamptic placentas. However, more studies are
      required to determine the role of TLRs in pregnancy immunology and to establish
      its relationship with preeclampsia.

PMID- 21843567
TI  - Calorie supply does not alleviate running-based taste aversion learning in rats.
AB  - Voluntary running establishes aversion to the paired taste in rats. A proposed
      mechanism underlying this taste aversion learning is energy expenditure caused by
      the running. The energy expenditure hypothesis predicts that running-based taste
      aversion should be alleviated by a calorie supply since this would compensate for
      the energy expended by running. Accordingly, running-based taste aversion would
      be less readily established to a caloric substance (20% sucrose solution) than to
      a noncaloric substance (0.2% sodium saccharin solution). Because the sucrose and
      saccharin aversions were equivalent in Experiment 1, the validity of the energy
      expenditure hypothesis was questioned. Experiments 2 and 3 also pose a problem
      for this hypothesis, as post-session calorie supply by glucose tablets failed to
      alleviate running-based aversion to salty water.

PMID- 21843568
TI  - Social norms and diet in adolescents.
AB  - We hypothesized that adolescents misperceive social norms for food consumption,
      and aimed to test this, and examine associations between perceived norms and
      dietary behaviours. School pupils (n=264) in the UK, aged 16-19 years, completed
      a questionnaire about their own attitudes to, and intake of, fruits and
      vegetables, unhealthy snacks and sugar-sweetened drinks, and their perceptions of
      their peers' attitudes to (injunctive norms), and intake of (descriptive norms),
      the same foods. Misperceptions were calculated from differences between perceived
      norms and median self-reports of peer groups. Respondents overestimated their
      peers' intake of snacks by 1.8 portions a week, and sugar-sweetened drinks by 5.2
      portions, and overestimated how positive their peers' attitudes were towards
      these behaviours. They underestimated their peers' consumption of fruits and
      vegetables by 3.2 portions per week and how positive their peers' attitudes were
      towards fruit and vegetables. Descriptive norms were strongly associated with
      intake of fruit and vegetables, sugar-sweetened drinks, and unhealthy snacks,
      explaining between 17% and 22% of the variance in consumption. There was no
      association between injunctive norms and intake. Descriptive norms indicated that
      misperceptions of peers' food intake were associated with respondents' own
      intake. Interventions to correct misperceptions have the potential to improve
      adolescents' diets.

PMID- 21843569
TI  - Molecular identification of ghrelin receptor (GHS-R1a) and its functional role in
      the gastrointestinal tract of the guinea-pig.
AB  - Ghrelin stimulates gastric motility in vivo in the guinea-pig through activation
      of growth hormone secretagogue receptor (GHS-R). In this study, we identified GHS
      R1a in the guinea-pig, and examined its distribution and cellular function and
      compared them with those in the rat. Effects of ghrelin in different regions of
      gastrointestinal tract were also examined. GHS-R1a was identified in guinea-pig
      brain cDNA. Amino acid identities of guinea-pig GHS-R1a were 93% to horses and
      85% to dogs. Expression levels of GHS-R1a mRNA were high in the pituitary and
      hypothalamus, moderate in the thalamus, cerebral cortex, pons, medulla oblongata
      and olfactory bulb, and low in the cerebellum and peripheral tissues including
      gastrointestinal tract. Comparison of GHS-R1a expression patterns showed that
      those in the brain were similar but the expression level in the gastrointestinal
      tract was higher in rats than in guinea-pigs. Guinea-pig GHS-R1a expressed in HEK
      293 cells responded to rat ghrelin and GHS-R agonists. Rat ghrelin was
      ineffective in inducing mechanical changes in the stomach and colon but caused a
      slight contraction in the small intestine. 1,1-Dimethyl-4-phenylpiperazinium and
      electrical field stimulation (EFS) caused cholinergic contraction in the
      intestine, and these contractions were not affected by ghrelin. Ghrelin did not
      change spontaneous and EFS-evoked [(3)H]-efflux from [(3)H]-choline-loaded ileal
      strips. In summary, guinea-pig GHS-R1a was identified and its functions in
      isolated gastrointestinal strips were characterized. The distribution of GHS-R1a
      in peripheral tissues was different from that in rats, suggesting that the
      functional role of ghrelin in the guinea-pig is different from that in other
      animal species.

PMID- 21843570
TI  - Ghrelin agonists impact on Fos protein expression in brain areas related to food
      intake regulation in male C57BL/6 mice.
AB  - Many peripheral substances, including ghrelin, induce neuronal activation in the
      brain. In the present study, we compared the effect of subcutaneously
      administered ghrelin and its three stable agonists: Dpr(3)ghr ([Dpr(N
      octanoyl)(3)] ghrelin) (Dpr - diaminopropionic acid), YA GHRP-6 (H-Tyr-Ala-His
      DTrp-Ala-Trp-DPhe-Lys-NH(2)), and JMV1843 (H-Aib-DTrp-D-gTrp-CHO) on the Fos
      expression in food intake-responsive brain areas such as the hypothalamic
      paraventricular (PVN) and arcuate (ARC) nuclei, the nucleus of the solitary tract
      (NTS), and area postrema (AP) in male C57BL/6 mice. Immunohistochemical analysis
      showed that acute subcutaneous dose of each substance (5mg/kg b.w.), which
      induced a significant food intake increase, elevated Fos protein expression in
      all brain areas studied. Likewise ghrelin, each agonist tested induced distinct
      Fos expression overall the PVN. In the ARC, ghrelin and its agonists specifically
      activated similarly distributed neurons. Fos occurrence extended from the
      anterior (aARC) to middle (mARC) ARC region. In the latter part of the ARC, the
      Fos profiles were localized bilaterally, especially in the ventromedial portions
      of the nucleus. In the NTS, all substances tested also significantly increased
      the number of Fos profiles in neurons, which also revealed specific location,
      i.e., in the NTS dorsomedial subnucleus (dmNTS) and the area subpostrema (AsP).
      In addition, cells located nearby the NTS, in the AP, also revealed a significant
      increase in number of Fos-activated cells. These results demonstrate for the
      first time that ghrelin agonists, regardless of their different chemical nature,
      have a significant and similar activating impact on specific groups of neurons
      that can be a part of the circuits involved in the food intake regulation.
      Therefore there is a real potency for ghrelin agonists to treat cachexia and food
      intake disorders. Thus, likewise JMV1843, the other ghrelin agonists represent
      substances that might be involved in trials for clinical purposes.

PMID- 21843571
TI  - Relationship between the 17q21 locus and adult asthma in a Czech population.
AB  - Several whole-genome association studies have shown a significant link between
      childhood asthma and the 17q12 chromosome region. We selected tagging single
      nucleotide polymorphisms (SNPs) in the ORMDL3 gene (17q12) to investigate gene
      variability in relation to adult allergic asthma and asthma/atopy traits in a
      Czech Caucasian population of adults. We conducted a case-control association
      study comprising 668 unrelated subjects (337 asthmatic and 331 control subjects).
      Four selected SNPs (rs17608925, rs12603332, rs8076131, and rs3169572) were
      genotyped using the TaqMan SNP Genotyping Assays. The single locus analysis
      showed only a borderline association between rs3169572 variant and asthma (p =
      0.030, p(corr) > 0.05). However, seven different haplotypes were identified;
      among them, the TTAA haplotype was marginally associated with asthma (p = 0.045,
      p(corr) > 0.05) and TCAG haplotype was significantly associated with asthma in
      males (p = 0.009, p(corr) < 0.05, odds ratio = 1.48, 95% confidence interval =
      1.10-2.00). In addition, associations between the ORMDL3 genotypes and the total
      IgE level (p = 0.05, p(corr) > 0.05) and hypersensitivity to the pollen (p =
      0.007, p(corr) < 0.05) were established. However, no relationship between ORMDL3
      SNPs and the pulmonary functions was found (p > 0.05). These findings suggest
      that the genetic variability in the 17q21 region may be one of the risk factors
      also for adult asthma, especially in male individuals.

PMID- 21843572
TI  - Transforming growth factor-beta1 variant Leu10Pro is associated with both lack of
      microfilariae and differential microfilarial loads in the blood of persons
      infected with lymphatic filariasis.
AB  - Antigen testing and ultrasound detection have shown that many persons are
      infected with Wuchereria bancrofti even though they do not have microfilariae
      (Mf) in the blood. To ascertain the role of human host immunogenetics on the lack
      of circulating Mf in the blood, 152 lymphatic filariasis (LF)-infected patients
      comprising 118 patients with microfilaremic (Mf+, patent) infection and 34
      patients with latent (Mf-, antigen-positive) infection were recruited and
      genotyped for association of single nucleotide polymorphisms of TGF-beta1 and
      differential Mf load and/or lack of Mf in the blood from infected persons in
      Ghana. An association was found between the TGF-beta1 Leu10Pro variant and lack
      of Mf in the blood. Patients with latent infection had a higher frequency of the
      Leu/Leu genotype than patients with patent infection (p = 0.03). Secondary
      analysis revealed an association among the three possible Leu10Pro genotypes and
      different Mf loads in the blood. In conclusion, the differential Mf loads and the
      lack of Mf in the blood of patients is likely to have a genetic basis. Because
      the adult worms are responsible for pathology, these results underscore the need
      for a review of using only Mf detection in blood smears for diagnosis of LF
      infection in endemic areas. This information is also important for the mapping
      and surveillance activities of national and global programs for elimination of
      LF.

PMID- 21843573
TI  - MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus
      infection.
AB  - Hepatitis C virus (HCV) has become a major public health issue and is prevalent
      in most countries. We examined several MASP2 functional polymorphisms in 104
      Brazilian patients with moderate and severe chronic hepatitis C using the primers
      set to amplify the region encoding the first domain (CUB1), a critical region for
      the formation of functional mannan-binding lectin (MBL)/MBL-associated serine
      proteases (MASP)-2 complexes, and the fifth domain (CCP2), which is essential for
      C4 cleavage of the MASP2 gene. We identified five single nucleotide polymorphisms
      in patients and controls: p. R99Q, p. D120G, p.P126L, p.D371Y, and p.V377A. Our
      results show that the p.D371Y variant (c.1111 G > T) is associated with
      susceptibility to HCV infection (p = 0.003, odds ratio = 6.33, 95% confidence
      interval = 1.85-21.70). Considered as a dominant function for the T allele, this
      variant is associated with high plasma levels of the MASP-2 in hepatitis C
      patients (p < 0.001). However, further functional investigations are necessary to
      understand the degree of involvement between MASP2 and the HCV susceptibility.

PMID- 21843574
TI  - Association of TAP 1 and 2 gene polymorphisms with human immunodeficiency virus
      tuberculosis co-infection.
AB  - Major histocompatibility complex (MHC) class I binding peptides are carried from
      cytosol to the lumen of the endoplasmic reticulum (ER) by transporter associated
      with antigen processing (TAP), an integral ER membrane protein composed of two
      subunits, TAP1 and TAP2. Polymorphism in TAP genes may influence these proteins
      further affecting the antigen peptide presentation, indirectly resulting in the
      viral escape mechanism from cell-mediated immunity in human immunodeficiency
      virus (HIV). Our aim was to study the influence of these polymorphism in study
      groups with HIV-tuberculosis (TB) (n = 110), TB (n = 105), and HIV (n = 130)
      compared with healthy controls (n = 183), using the tetraprimer amplification
      refractory mutation system (ARMS)-polymerase chain reaction method. Our results
      demonstrated that the GG genotype at TAP1 position 333 and GA genotype at TAP1
      position 637 were positively associated with HIV-TB co-infection and these
      genotypes may act as a risk factor for developing TB co-infection in HIV-positive
      individuals.

PMID- 21843575
TI  - Physico-chemical properties of Salmonella typhi Vi polysaccharide-diphtheria
      toxoid conjugate vaccines affect immunogenicity.
AB  - In this study it was demonstrated that the immunogenicity of Vi polysaccharide
      diphtheria toxoid conjugates was related to the physical and chemical structure
      of the conjugate. Conjugates were prepared in two steps, firstly binding adipic
      acid dihydrazide (ADH) spacer molecules to diphtheria toxoid (DT) carrier protein
      then secondly binding varying amounts of this derivatized DT to a fixed amount of
      Vi capsular polysaccharide purified from Salmonella enterica Serovar Typhi. As
      the amount of DT bound to the Vi increased the size of the conjugate increased
      but also the degree of cross-linking increased. The immunogenicity of the
      conjugates was tested in mice and measured by ELISA for anti Vi and anti DT IgG
      responses, and the results revealed a trend that as the amount of DT bound to the
      Vi increased the anti Vi responses increased. This study establishes a
      correlation between physico-chemical characteristics of the conjugate and the
      magnitude of the anti Vi and anti DT responses.

PMID- 21843576
TI  - Prevention of tick-borne encephalitis by FSME-IMMUN vaccines: review of a
      clinical development programme.
AB  - The need for highly effective tick-borne encephalitis (TBE) vaccines has
      increased globally due to a variety of factors including climate, social,
      economic and demographic changes, which are thought to have promoted the
      expansion of the endemic region of TBE viruses. The first TBE vaccine, FSME-IMMUN
      Inject, was introduced in the 1970s and has been continually improved since then
      to enhance both its safety and immunogenicity. The current formulation was
      established in 2001 and is marketed as FSME-IMMUN. This review summarizes
      findings of the clinical development programme since 2001 regarding determination
      of the optimal dose, conventional and rapid vaccination schedules, vaccination in
      adults, the elderly and special patient populations, safety, immunogenicity, and
      immunopersistence in adults and children, comparison of FSME-IMMUN with another
      commercially available TBE vaccine as well as post-marketing vaccination outcome.
      This successful research programme demonstrated the strong immunogenicity and
      continued safety of the FSME-IMMUN vaccine, which is further confirmed by the
      performance reported under field conditions.

PMID- 21843578
TI  - Hospital-based study of the economic burden associated with rotavirus diarrhea in
      eastern China.
AB  - Rotavirus infection is one of the most common causes of severe diarrhea in China.
      To evaluate the economic burden associated with rotavirus infection of children
      in China, we combined data on the disease burden of rotavirus-associated costs
      for samples comprising 832 outpatients and 604 inpatients from five seaside
      cities. The average social costs and direct medical costs for rotavirus
      associated admissions were calculated to be US $61.64 and US $40.73 for
      outpatients, and US $684.15 and US $559.48 for inpatients, respectively, from
      October 1, 2006 to December 1, 2007. On average, the private cost ranged from US
      $54.64 for outpatients to US $454.24 for inpatients when children suffered from
      rotavirus infection. Accordingly, this cost accounted for 35.19-293% of the
      monthly income of an unskilled or service worker. We estimated that the annual
      number of children with rotavirus diarrhea was 12.10 million. Consequently, the
      total annual direct cost, total annual social cost, and total annual private cost
      were US $271.4 million, US $365.0 million, and US $290.0 million, respectively.
      Furthermore, rotavirus diarrhea affected children's behavior and emotions, which
      had a great influence on the caretakers' quality of life. These data indicate the
      potential requirement for a safe and effective rotavirus vaccine to reduce the
      economic burden associated with rotavirus disease.

PMID- 21843579
TI  - Immune response of Atlantic salmon to recombinant flagellin.
AB  - Many viral vaccines used in aquaculture are unable to stimulate an appropriate
      level of immunity to withstand infection. By targeting specific components of the
      immune system it may be possible to trigger stronger, more effective responses to
      antigens. Flagellin has the ability to stimulate both the soluble and membrane
      bound forms of toll-like receptor 5 (TLR5) in salmon leading to a proinflammatory
      response and activation of both the innate and adaptive immune system. In this
      study flagellin (FlaD from Vibrio anguillarum) was recombinantly produced in two
      forms, full-length (FDL) and a truncated form (FDS) with portions of the N- and C
      termini removed to prevent polymerization. FDS was used to produce an antibody
      that was able to bind both forms of flagellin in immunoblot analysis. In cell
      culture using COS-7 cells, FDL was shown to stimulate the NF-kappaB pathway more
      effectively than FDS. Both forms of flagellin were used as an adjuvant with the
      antigen LPH (Hemocyanin from Limulus polyphemus hemolymph) in an immunization
      dose-response study. FDS and FDL stimulated the innate immune system of salmon
      inducing proinflammatory effects on days 2, 4 and 7 and the gene expression of
      important cytokines such as TNFalpha, IL-6, IL-8, and IL-1beta were significantly
      up-regulated (p<0.05) in the spleen. TLR5S was more highly up-regulated than
      TLR5M indicating that the soluble form of TLR5 may play an important role in the
      innate immune response in salmon. ELISA analysis showed that the use of flagellin
      as an adjuvant with LPH was not able to significantly induce flagellin or LPH
      antibodies. This study shows that flagellin has the potential to be a highly
      effective adjuvant for salmon immunization, but further research is needed.

PMID- 21843580
TI  - Source imaging of P300 auditory evoked potentials and clinical correlations in
      patients with posttraumatic stress disorder.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with abnormal
      information processing. The P300 component of event-related potentials (ERPs) is
      known to be a useful marker of information processing. The purposes of this study
      were to determine the P300 current source density in PTSD patients, and its
      relationship with symptom severity. METHODS: ERPs were recorded in 30 PTSD
      patients and 33 healthy controls while participants were performing the auditory
      oddball task. We compared P300 current source density data--obtained by
      standardized low-resolution brain electromagnetic tomography (sLORETA)--between
      the two groups. The correlation between P300 current source density and clinical
      symptoms (as evaluated using the Korean version of the Structured Interview for
      PTSD--K-SIPS and Davidson Trauma Scale--K-DTS) was conducted. RESULTS: In PTSD
      patients, the current source density of P300 is significantly reduced in the
      inferior frontal gyrus, precentral gyrus, insula, and anterior cingulate compared
      to healthy controls. Total K-DTS scores were correlated with the P300 current
      source density in the posterior cingulate gyrus. The K-SIP B items (re
      experiencing) and K-SIB D items (increased arousal) were positively correlated
      with P300 current source densities in several brain regions located in the
      frontal, parietal, and temporal lobe (p<0.05). Conversely, the K-SIP C items
      (avoidance and numbing) were negatively correlated with P300 current source
      densities in the superior and middle frontal gyri in the frontal lobes (p<0.05).
      CONCLUSION: The P300 current source densities reflected the pathophysiology of
      PTSD patients. PTSD symptoms were related to different neural activities,
      depending on their symptom characteristics.

PMID- 21843581
TI  - Exopolysaccharide of Laetiporus sulphureus var. miniatus downregulates LPS
      induced production of NO, PGE2, and TNF-alpha in BV2 microglia cells via
      suppression of the NF-kappaB pathway.
AB  - Our previous study showed that the exopolysaccharide (EPS) of Laetiporus
      sulphureus var. miniatus was well characterized and prevented cell damage in
      streptozotocin-induced apoptosis. However, little is known about the molecular
      mechanisms underlying its anti-inflammatory effects. Therefore, we attempted in
      this study to determine whether EPS induces a significant inhibition of pro
      inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2
      microglia cells. Our results showed that EPS significantly inhibited LPS-induced
      pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E(2)
      (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha), without any significant
      cytotoxicity. EPS also downregulated mRNA and protein expression of inducible NO
      synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-alpha in LPS-induced BV2
      microglia cells. Our data also revealed that EPS treatment significantly reduced
      translocation of nuclear factor-kappaB (NF-kappaB) subunit p65 and its DNA
      binding activity in LPS-stimulated BV2 microglia cells. Furthermore, we confirmed
      by using proteasome inhibitor N-acetyl-l-cysteine (NAC), that the inhibition of
      NF-kappaB activity influenced the expression of pro-inflammatory genes in LPS
      induced BV2 microglia cells. As expected, NAC suppressed the expression of iNOS,
      COX-2, and TNF-alpha by blocking proteasome-mediated degradation. Taken together,
      our data indicate that EPS inhibits the expression of pro-inflammatory mediators
      by suppressing NF-kappaB activity.

PMID- 21843582
TI  - Comparison of dry, wet and microwave digestion methods for the multi element
      determination in some dried fruit samples by ICP-OES.
AB  - The aim of this study was used to investigate the level of trace metals (Ba, Pb,
      Cd, Mn, Cr, Co, Ni, Cu, Mn, Zn, Sr and Fe) in some dried fruits (Prunus domestica
      L., Ficus carica L., Morus alba L., Vitis vinifera L., Prunus armeniaca L., and
      Malus domestica) samples from Turkey. Trace elements were determined by ICP-OES
      after dry, wet and microwave digestion methods in dried fruit samples. Validation
      of the proposed method was carried out by using a NIST-SRM 1515-Apple Leaves
      certified reference material. Element concentrations in dried fruit samples were
      0.33-1.77 (Ba), 0.12-0.54 (Cd), 0.25-1.03 (Co), 0.45-2.30 (Cr), 0.43-2.74 (Cu),
      0.56-4.87 (Mn), 0.61-2.54 (Ni), 0.40-2.14 (Pb), 2.16-6.54 (Zn), 0.83-12.02 (Al),
      11.82-40.80 (Fe) and 0.16-6.34 (Sr) MUg/g. The analytical parameters show that
      the microwave oven digestion procedure provided best results as compared to the
      wet and dry digestion procedures. The results were compared with the literature
      values.

PMID- 21843583
TI  - 1H NMR study of monocrotaline and its metabolites in human blood.
AB  - Monocrotaline (MCT) is a naturally occurring hepatotoxic pyrrolizidine alkaloid
      found in plants. This investigation is aimed at furthering the understanding of
      the role of blood in mediating the transport of MCT and its reactive metabolites
      in humans. Reactions of monocrotaline and its metabolites, dehydromonocrotaline
      (DHM), retronecine (RET) and dehydroretronecine (DHR) with human blood plasma,
      red blood cells (RBCs), and whole blood were studied in vitro by proton nuclear
      magnetic resonance spectroscopy. In plasma MCT remained intact and weakly
      associated with plasma proteins, and DHM was rapidly hydrolyzed releasing necic
      and lactone acids, and the reactive pyrrolic metabolite. MCT and its metabolite
      DHM were internalized in RBCs to the extent of 46.0% and 48.9% respectively in 30
      min. No polymerization of DHR was observed when incubated with plasma and RBCs.
      The data clearly showed that both human plasma and RBCs could be the carriers for
      the transportation of MCT and its metabolites, DHM, RET and DHR between organs
      and could stabilise the reactive MCT metabolite DHR.

PMID- 21843584
TI  - Alpha-lipoic acid protects against myocardial ischemia/reperfusion injury via
      multiple target effects.
AB  - Myocardial ischemia/reperfusion (MI/R) is a major cause for the events of
      cardiovascular disease. Oxidative stress plays a critical role in the development
      of ischemia/reperfusion (IR) injury. As a potent antioxidant, alpha-lipoic acid
      (LA) has been shown to provide a benefit for the inhibition of IR injury and
      inhibit reactive oxygen species (ROS) generation during MI/R in rats. However,
      the mechanism on the protective effect of LA is still to be clarified. The
      present study was aimed to investigate the protective effect of LA against MI/R
      injury and its mechanisms. We found that 2h of myocardial ischemia followed by
      different time periods of reperfusion resulted in significant increase of
      creatine kinase (CK) activity. MI/R also significantly promoted oxidative stress
      and decreased the activities of antioxidant enzymes. In addition, apoptosis and
      inflammatory response were activated and aggravated in a time-dependent manner by
      MI/R. All these alterations induced by MI/R were attenuated by the administration
      of LA 30 min before reperfusion. These results suggested that LA played a
      protective effect against MI/R injury via antioxidant, anti-apoptotic and anti
      inflammatory effects. These findings may significantly better the understanding
      of the pharmacological actions of LA and advance therapeutic approaches to MI/R
      injury and cardiovascular diseases.

PMID- 21843585
TI  - Ellipticine induces apoptosis in human endometrial cancer cells: the potential
      involvement of reactive oxygen species and mitogen-activated protein kinases.
AB  - Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been shown to
      exhibit antitumor activity in several human malignant tissues including breast,
      thyroid, and ovarian cancers. The antitumor activity of ellipticine is thought to
      be primarily mediated by the induction of DNA damage through the inhibition of
      topoisomerase II and formation of DNA adducts. The human endometrium is known to
      express topoisomerase II. However, the apoptogenic activity of ellipticine and
      the mechanisms underlying its action have not been investigated in endometrial
      cancer cells. In the present study, exposure to ellipticine (1-10MUM) was shown
      to induce apoptosis in RL95-2 human endometrial cancer cells. Ellipticine-induced
      cell death was associated with the accumulation of cells in the G2/M phase of the
      cell cycle and was accompanied by depolarization of the mitochondrial membrane
      potential, release of cytochrome c and apoptosis-inducing factor (AIF) from the
      mitochondrial membrane, and caspase activation. The production of intracellular
      reactive oxygen species (ROS) was increased and sustained at high levels during
      ellipticine treatment. Subsequent to ROS accumulation, extracellular-signal
      regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were activated in
      ellipticine-treated cells. Release of AIF from the mitochondria appeared to be
      affected by caspases, ROS, and ERK. The present data show that the treatment of
      RL95-2 cells with ellipticine induces apoptosis, ellipticine-induced apoptosis is
      mediated by ROS and the activation of MAPKs, and release of AIF is involved in a
      caspase-independent pathway. These results demonstrate the potential of
      ellipticine as a therapeutic strategy for the treatment of human endometrial
      cancers.

PMID- 21843586
TI  - Nickel(II) induced JNK activation-regulated mitochondria-dependent apoptotic
      pathway leading to cultured rat pancreatic beta-cell death.
AB  - Nickel (Ni), a well-known toxic metal, is widely used in electroplating and alloy
      production. It is also significantly implicated in industrial and environmental
      pollution caused by uncontrolled industrial and municipal discharges. In this
      study, we characterized and investigated the cytotoxic effects of Ni exposure and
      their probable toxicological mechanisms in the pancreatic beta-cells. The results
      showed that it was significantly decreased cell viability after exposing
      pancreatic beta-cell-derived RIN-m5F cells to NiCl(2) for 24h in a dose-dependent
      manner. NiCl(2) also increased sub-G1 hypodiploid cells and Annexin V-Cy3 binding
      population in RIN-m5F cells, indicating that it has apoptosis-inducing ability.
      Moreover, the exposure of RIN-m5F cells to NiCl(2) induced distinct signals of
      mitochondria-dependent apoptosis, including mitochondrial dysfunction (the
      disruption of mitochondrial membrane potential (MMP) and increase in
      mitochondrial cytochrome c release into the cytosol), Bak and Bid mRNA up
      regulation, and activation of caspase-3, caspase-7, and caspase-9, and poly(ADP
      ribose) polymerase (PARP) degradation. In addition, NiCl(2) also markedly induced
      the activation of c-Jun N-terminal kinases (JNK), but not of extracellular signal
      regulated kinase (ERK)1/2 and p38. These NiCl(2)-induced apoptosis-related
      signaling responses could be effectively reversed by specific JNK inhibitor
      SP600125. To the best of our knowledge, this study is the first to show that Ni
      causes pancreatic beta-cell death through a JNK activation-regulated mitochondria
      dependent apoptosis-signaling pathway.

PMID- 21843587
TI  - Characterization of steroid hormone receptor activities in 100 hydroxylated
      polychlorinated biphenyls, including congeners identified in humans.
AB  - Hydroxylated polychlorinated biphenyls (OH-PCBs), major metabolites of PCBs, have
      been reported to act as estrogen receptor alpha (ERalpha) agonists or
      antagonists. However, little concern has been paid to the ability of OH-PCBs to
      interfere with other steroid hormone receptors such as ERbeta, androgen receptor
      (AR) or glucocorticoid receptor (GR). In this study, we characterized the
      agonistic and antagonistic activities of available 100 OH-PCBs (39 ortho-, 24
      meta-, and 37 para-OH compounds), including some congeners identified in humans,
      against human ERalpha/beta, AR, and GR using in vitro reporter gene assays. In
      the ERalpha assay, 45 and 9 of the 100 OH-PCBs tested showed agonistic and
      antagonistic activities, respectively. In the ERbeta assay, 45 and 6 compounds
      showed agonistic and antagonistic activities, respectively. In the AR and GR
      assays, although none of the compounds tested showed agonistic activity, 83 and
      30 of the 100 OH-PCBs showed antagonistic activity, respectively. These AR and/or
      GR antagonistic compounds had various patterns of substituent in the structure,
      while relatively potent ERalpha/beta agonistic and antagonistic compounds
      possessed para- and ortho-OH structures, respectively. Three OH-PCBs,
      predominantly identified in human tissues, showed little ERalpha/beta or AR
      activities, apart from the weak ERalpha and/or GR antagonistic activity observed
      in 4-OH-CB107 and 4-OH-CB187. Taken together, these results suggest that a large
      number of OH-PCBs might act as agonists and/or antagonists against ERalpha/beta,
      AR and GR.

PMID- 21843588
TI  - Identification and characterisation of Kunitz-type plasma kallikrein inhibitors
      unique to Oxyuranus sp. snake venoms.
AB  - As part of a wider study on Australian snake venom components, we have identified
      and characterised Kunitz-type protease inhibitors from the venoms of Oxyuranus
      scutellatus and Oxyuranus microlepidotus (Australian taipans) with plasma
      kallikrein inhibitory activity. Each inhibitor had a mass of 7 kDa and was
      purified from the venom as part of a protein complex. Mass spectrometry and N
      terminal sequencing was employed to obtain amino acid sequence information for
      each inhibitor and a recombinant form of the O. scutellatus inhibitor, termed
      TSPI, was subsequently expressed and purified. TSPI was investigated for
      inhibition against a panel of 12 enzymes involved in haemostasis and estimates of
      the K(i) value determined for each enzyme. TSPI was found to be a broad spectrum
      inhibitor with most potent inhibitory activity observed against plasma kallikrein
      that corresponded to a K(i) of 0.057 +/- 0.019 nM. TSPI also inhibited
      fibrinolysis in whole blood and prolonged the intrinsic clotting time. These
      inhibitors are also unique in that they appear to be found only in Oxyuranus sp.
      venoms.

PMID- 21843590
TI  - Small RNAs derived from longer non-coding RNAs.
AB  - Posttranscriptional gene regulation by small RNAs and its crucial impact on
      development, apoptosis, stem cell self-renewal and differentiation gained
      tremendous scientific attention since the discovery of RNA interference (RNAi)
      and microRNAs (miRNAs). However, in the last few years, many more examples for
      regulatory small RNAs were discovered, some of them even with miRNA-like
      functions. Even though these small RNA molecules were previously thought to be
      mere artifacts accumulating during the preparation of RNA libraries, advances in
      sequencing technology revealed that small RNAs derive from hairpin-fold RNA
      structures, for example. Mirtrons, short hairpin RNAs or small RNAs that are
      processed from longer non-coding RNAs such as tRNAs or snoRNAs have been found
      recently and some of them might be involved in the regulation of gene expression
      in different organisms. Furthermore, small RNAs originating from transposable
      elements, heterochromatic regions or convergent transcription units forming
      endogenous short interfering RNAs (endo-siRNAs) are the somatic equivalents of
      the germline-specific Piwi-interacting RNAs (piRNAs) in mediating transposon
      silencing. This review will focus on several recent findings that have added new
      aspects to small RNA-guided gene silencing.

PMID- 21843589
TI  - Non-coding RNA and antisense RNA. Nature's trash or treasure?
AB  - Although control of cellular function has classically been considered the
      responsibility of proteins, research over the last decade has elucidated many
      roles for RNA in regulation of not only the proteins that control cellular
      functions but also for the cellular functions themselves. In parallel to this
      advancement in knowledge about the regulatory roles of RNA there has been an
      explosion of knowledge about the role that epigenetics plays in controlling not
      only long-term cellular fate but also the short-term regulatory control of genes.
      Of particular interest is the crossover between these two worlds, a world where
      RNA can act out its part and subsequently elicit chromatin modifications that
      alter cellular function. Two main categories of RNA are examined here, non-coding
      RNA and antisense RNA both of which perform vital functions in controlling
      numerous genes, proteins and RNA itself. As the activities of non-coding and
      antisense RNA in both normal and aberrant cellular function are elucidated, so
      does the number of possible targets for pharmacopeic intervention.

PMID- 21843591
TI  - Optimal control analysis of a malaria disease transmission model that includes
      treatment and vaccination with waning immunity.
AB  - We derive and analyse a deterministic model for the transmission of malaria
      disease with mass action form of infection. Firstly, we calculate the basic
      reproduction number, R(0), and investigate the existence and stability of
      equilibria. The system is found to exhibit backward bifurcation. The implication
      of this occurrence is that the classical epidemiological requirement for
      effective eradication of malaria, R(0)<1, is no longer sufficient, even though
      necessary. Secondly, by using optimal control theory we derive the conditions
      under which it is optimal to eradicate the disease and examine the impact of a
      possible combined vaccination and treatment strategy on the disease transmission.
      When eradication is impossible, we derive the necessary conditions for optimal
      control of the disease using Pontryagin's Maximum Principle. The results obtained
      from the numerical simulations of the model show that a possible vaccination
      combined with effective treatment regime would reduce the spread of the disease
      appreciably.

PMID- 21843592
TI  - Evaluation of intermolecular forces in a circulating system.
AB  - Intercellular interactions, which are mediated by a variety of complex
      intercellular molecules through the processes of formation and dissociation of
      molecular bonds, play a critical role in regulating cellular functions in
      biological systems. Various approaches are applied to evaluate intercellular or
      molecular bonding forces. To quantify the intermolecular interaction forces, flow
      chamber has become a meaningful technique as it can ultimately mimic the cellular
      microenvironment in vivo under physiological flow conditions. Hydrodynamic forces
      are usually used to predict the intercellular forces down to the single molecular
      level. However, results show that only using hydrodynamic force will overestimate
      up to 30% of the receptor-ligand strength when the non-specific forces such as
      Derjaguin-Landau-Verway-Overbeek (DLVO) forces become un-neglected. Due to the
      nature of high ion concentration in the physiological condition, electrostatic
      force is largely screened which will cause DLVO force unbalanced. In this study,
      we propose to take account of the DLVO force, including van der Waals (VDW) force
      and electrostatic force, to predict the intermolecular forces of a cell doublet
      and cell-substrate model in a circulating system. Results also show that the DLVO
      force has a nonlinear effect as the cell-cell or cell-substrate distance changes.
      In addition, we used the framework of high accuracy hydrodynamic theories proved
      in colloidal systems. It is concluded that DLVO force could not be ignored in
      quantitative studies of molecular interaction forces in circulating system. More
      accurate prediction of intercellular forces needs to take account of both
      hydrodynamic force and DLVO force.

PMID- 21843593
TI  - Hepatocyte growth factor (HGF) regulates blood-testis barrier (BTB) in adult
      rats.
AB  - We have studied the effects of HGF on BTB dynamics in adult rats. We demonstrate
      that, at stages VII-VIII of the epithelium wave when germ cells traverse the BTB,
      HGF reduces the levels of occludin and influences its distribution pattern and
      assembling. Moreover, we report that, at stages VII-VIII, HGF significantly
      increases the amount of active TGF-beta and the amount of uPA present in the
      tubules. For the first time we report that, in the same stages, HGF reduces the
      amount of actin present in the BTB region, in which occludin levels are highest,
      and modifies the morphology of the actin cytoskeleton network. At the level of
      maximal intensity of occludin fluorescence, we report that HGF also modifies the
      colocalization of occludin and actin. Lastly, we demonstrate that HGF is
      maximally expressed at stages VII-VIII, whereas its levels fall in the subsequent
      stages.

PMID- 21843594
TI  - A visual field dependent architecture for second order motion processing.
AB  - The visual system exploits a cortical hierarchy to process complex inputs such as
      those defined by modulations of motion and/or texture. One class of visual
      stimuli, composed of alternate stripes of opposing motion requires at least 2
      separate stages of computation within this cortical hierarchy, thought to involve
      cortical area V1 and extra-striate regions like global motion area MT
      respectively. Using a psychophysical task, we characterise sensitivity to such
      stimuli containing periodic spatial modulations of motion gradients as a function
      of the ratio of the spatial parameters at the two processing levels by
      manipulating the spatial properties of the carrier and modulator. We find band
      passed functions for foveal stimulus presentations showing an optimum sensitivity
      at ratios in the range of r<=10, informative of the coupling relationship between
      frequency channels at the carrier and modulator levels. An annulus stimulus
      (excluding the fovea) with a radius of 15.5 degrees  exhibited optima of
      sensitivity at r>15. This difference in the optimal coupling between filtering
      stages reflects a processing architecture that changes with eccentricity,
      consistent with the previously observed smaller differences between mean
      receptive field sizes in striate and extra-striate filtering stages in the fovea
      compared to the periphery. This is also important for visual psychophysics when
      comparing sensitivity for first and second order stimuli across retinal
      eccentricity.

PMID- 21843595
TI  - Profiles of SUMO and ubiquitin conjugation in an Alzheimer's disease model.
AB  - Alzheimer's disease (AD) is a major cause of disability in the elderly. The
      formation of senile plaques and neurofibrillary tangles are the main hallmarks of
      the disorder, whereas synaptic loss best correlates to the progressive cognitive
      decline. Interestingly, some of the proteins involved in these pathophysiological
      processes have been reported to be subject to posttranslational modification by
      ubiquitin and/or the small ubiquitin-like modifier (SUMO). Here we investigated
      global changes in protein SUMOylation and ubiquitination in vivo in a model of
      AD. We used Tg2576 transgenic mice, which overexpress a mutated human amyloid
      precursor protein (APP) gene implicated in familial AD. As expected, APP protein
      levels were dramatically increased in the hippocampus, cortex and cerebellum of
      Tg2576 mice. A significant increase in the global level of ubiquitinated proteins
      was observed in the hippocampus of Tg2576 mice. Significant or close to
      significant changes in individual bands of SUMO-1 or SUMO-2/3 conjugation were
      apparent in all brain regions investigated, although global levels were unaltered
      between wild-type and transgenic mice. Levels of SUMO-specific conjugating and
      deconjugating enzymes, UBC9 and SENP-1 were also unaltered in any of the brain
      regions analysed. Surprisingly, given the well-documented loss of synaptic
      function, total levels of the excitatory AMPA and kainate receptors were
      unaffected in the Tg2576 mice. These results suggest that alterations in SUMO
      substrate conjugation may occur and that global posttranslational modifications
      by ubiquitin may play an important role in the mechanisms underlying AD.

PMID- 21843596
TI  - Antinociceptive effects of neurotropin in a rat model of central neuropathic
      pain: DSP-4 induced noradrenergic lesion.
AB  - Neurotropin is a nonprotein extract isolated from inflamed skin of rabbits
      inoculated with vaccinia virus, and used for treatment of neuropathic pain. In
      the present study, we have determined whether neurotropin could exert
      antinociceptive action using the central neuropathic pain model that we recently
      established. Rats were randomly allocated to 3 groups: Sham group (n=20), DSP-4
      [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine] group (50mg/kg ip, n=18), and DSP
      4+5,7-DHT [5,7-dihydroxytryptamine] group (ip DSP-4 50mg/kg+icv 5,7-DHT 200MUg,
      n=18). In Sham, DSP-4 and DSP-4+5,7-DHT groups, the effects of ip neurotropin
      (100NU/Kg) on hot-plate latency in rats with no lesion, noradrenergic neuron
      depletion and both noradrenergic and serotonergic neuronal depletion were
      studied, respectively. Rats in each group were subdivided equally to 2 subgroups:
      saline and neurotropin. After completion of the hot-plate tests, each rat was
      decapitated, the cerebral cortex was dissected from its internal structure for
      measurement of norepinephrine contents. Hot-plate latency significantly decreased
      by ~40% 10 days after ip DSP-4 or after ip DSP-4 and 5,7-DHT. Norepinephrine
      contents in DSP-4 treated rats (55.6+/-6.3ng/ng tissue) and DSP-4+5,7-DHT treated
      rats (35.3+/-6.3ng/ng tissue) were significantly lower than those in intact rats
      (131.6+/-5.7ng/ng tissue, p<0.01). Neurotropin significantly increased the area
      under the curve (AUC) of the hot-plate latency in the DSP-4 and DSP-4+5,7-DHT
      groups but not in the Sham group. There was a significant correlation between AUC
      and norepinephrine contents in saline subgroup (p<0.01, r=0.597) but not in
      neurotropin subgroup in DSP-4 group. Neurotropin exerted an antinociceptive
      effect in DSP-4 induced central neuropathic pain. The present data suggest
      neuronal pathways other than descending inhibitory noradrenergic and serotonergic
      systems may be involved in neurotropin mediated antinociception.

PMID- 21843598
TI  - DARPP-32 and Akt regulation in ethanol-preferring AA and ethanol-avoiding ANA
      rats.
AB  - Ethanol and other addictive drugs affect many intracellular phosphorylation and
      dephosphorylation cascades. These cascades are thought to be highly important in
      the regulation of neuronal activity. The present experiments characterized the
      regulation of three key signaling molecules, DARPP-32 (dopamine and cAMP
      regulated phosphoprotein, 32kDa), Akt kinase and ERK1/2 (extracellular signal
      regulated kinase 1 and 2) in ethanol-preferring AA (Alko, alcohol) and ethanol
      avoiding ANA (Alko, non-alcohol) rat lines. Radioactive in situ hybridization was
      used in drug naive animals and Western blotting after acute ethanol
      administration in striatum, hippocampus and prefrontal cortex. The mRNA levels of
      DARPP-32 in striatal areas were higher in ANA rats than in AA rats. There was no
      difference in the striatal enriched phosphatase (STEP61), the downstream target
      of DARPP-32 expression between the rat lines. Ethanol (1.5g/kg) increased
      phosphorylation of DARPP-32 at threonine 34 in both AA and in ANA rats indicating
      that acute ethanol activates DARPP-32 similarly in these rat lines. The
      expression of Akt kinase was higher in the CA1 of hippocampus in ANA than in AA
      rats and acute ethanol activated Akt in hippocampus in ANA but not in AA rats. No
      significant alterations in the regulation of ERK1/2 were found in either rat
      line. Our findings suggest that DARPP-32 and Akt are regulated by ethanol and
      differences in the regulation of these molecules might contribute to the
      dramatically different ethanol drinking patterns seen in AA and ANA rats.

PMID- 21843597
TI  - SOD1 overexpression improves features of the oligodendrocyte precursor response
      in vitro.
AB  - Spinal cord injury (SCI) produces a significant loss of oligodendrocytes (OL) and
      demyelination. The oligodendrocyte precursor cells (OPCs) response includes a
      group of cellular changes in OPCs that are directed to replenish OL loss from the
      injury. However, this adaptive response is hampered and OPCs eventually die or
      fail to differentiate to mature and functional OL. In this study, we wanted to
      evaluate if overexpression of human superoxide dismutase 1 (hSOD1) in OPCs from
      the SOD1 transgenic rat could improve some of the features of the OPC response in
      vitro. We found that hSOD1 overexpression increases the proliferation of OPCs and
      accelerates their differentiation to mature OL in vitro. Furthermore, hSOD1
      overexpression reduces oxidative stress-mediated death in OPCs. These results
      suggest hSOD1 as a therapeutic target to increase OPC response success and
      potentially, OL replacement and remyelination after SCI.

PMID- 21843599
TI  - Asparagus racemosus competitively inhibits in vitro the acetylcholine and
      monoamine metabolizing enzymes.
AB  - Asparagus racemosus (AR) has earlier been reported to possess antidepressant
      activity possibly mediated through the monoaminergic system, and nootropic and
      anti amnestic activities possibly through the cholinergic system. In the present
      study to further understand the mechanism of action, we evaluated the kinetics of
      acetyl (AChE) and butyryl (BuChE) cholinesterases, and monoamine oxidase (MAO-A
      and B) enzyme inhibitory activities of different fractions of AR. The results
      showed that methanolic extract of AR (MAR) significantly inhibited cholinesterase
      and MAO activities as compared to hexane (HAR) and chloroform (CAR) extracts of
      AR as evident from the IC(50) values. The kinetic analysis of enzyme inhibition
      of MAR shows that the V(max) does not change with different concentrations of MAR
      but the K(m) value increases. This indicates that MAR is a non-selective
      competitive inhibitor for both cholinesterase and monoamine oxidase enzymes.
      Evaluation of K(i) values show that MAR inhibited these enzymes less potently
      compared to the respective standard drugs. There seems to be a positive
      correlation between the saponin content and, cholinesterase and monoamine
      inhibitory activities as MAR had 62.20% of saponins, whereas HAR and CAR had no
      measurable saponin content. The non-selective competitive inhibitory activity on
      cholinesterase and monoamine oxidase enzymes can explain many reported
      neuropharmacological activities of AR. AR apart being used as a drug is also used
      as a food. As such AR may have potential drug-drug, drug-food and food-food
      interactions with drugs and foods sharing the cholinergic and monoaminergic
      pathways.

PMID- 21843600
TI  - A novel SCN1A missense mutation causes generalized epilepsy with febrile seizures
      plus in a Chinese family.
AB  - Generalized epilepsy with febrile seizures plus (GEFS(+)) is a common familial
      epilepsy syndrome, which generally develops in childhood. GEFS(+) is caused by
      mutations in the sodium-channel alpha1-subunit (SCN1A). In this report, we
      investigated a Chinese family with an autosomal dominant form of GEFS(+). The
      affected GEFS(+) patients in this family displayed significant inter-family
      clinical heterogeneity. Linkage analysis localized the disease-causing gene to
      chromosome 2q24, where SCN1A is located. Furthermore, DNA sequencing of the whole
      coding region of SCN1A revealed a novel heterozygous nucleotide substitution
      (c.577C>T) causing a missense mutation (p.L193F) in the S3 segment of SCN1A
      domain D1. Our results expand the spectrum of SCN1A mutations and provide novel
      insights between the SCN1A mutations and the clinical variations of GEFS(+).

PMID- 21843601
TI  - Brain-derived neurotrophic factor (BDNF) infusion restored astrocytic plasticity
      in the hippocampus of a rat model of depression.
AB  - Brain-derived neurotrophic factor (BDNF) is closely associated with hippocampal
      plasticity in psychiatric disorders. Glial cells (particularly astrocytes) are
      the most abundant cell type in the central nervous system. Previous studies have
      demonstrated that distinct alterations of astrocytes are associated with major
      depressive disorder, but there is a paucity of data describing whether such
      alterations of astrocytic plasticity are present in depressive-like rat
      hippocampus after BDNF administration. In this paper, we investigated the effects
      of chronic unpredictable mild stress (CUMS) and BDNF infusion on astrocyte
      immunoreactivity in rat hippocampus using sucrose preference test, open field
      test, and Western blot analysis. Results revealed that CUMS induced anhedonic
      like behaviors in sucrose consumption and open field performances, which were
      partially reversed by BDNF infusion. Moreover, CUMS produced decreased glial
      fibrillary acidic protein (GFAP) expression and increased s100 calcium binding
      protein b (s100b) expression in rat hippocampus, which were partially rescued by
      BDNF administration. Therefore, BDNF might restore astrocyte immunoreactivity in
      depressive-like rat hippocampus, providing insights into the potential
      pharmacological role of BDNF in stress-related disorders.

PMID- 21843602
TI  - The thermodynamic and binding properties of the transferrins as studied by
      isothermal titration calorimetry.
AB  - BACKGROUND: In mammals, serum-transferrins transport iron from the neutral
      environment of the blood to the cytoplasm by receptor-mediated endocytosis.
      Extensive in-vitro studies have focused on the thermodynamics and kinetics of
      Fe(3+) binding to a number of transferrins. However, little attention has been
      given to the thermodynamic characterization of the interaction of transferrin
      with its receptor. SCOPE OF REVIEW: Iron-loaded transferrin (Tf) binds with high
      affinity to the specific transferrin receptor (TfR) on the cell surface. The Tf
      TfR complex is then internalized via receptor mediated endocytosis into an
      endosome where iron is released. Here, we provide an overview of recent studies
      that have used ITC to quantify the interaction of various metal ions with
      transferrin and highlight our current understanding of the thermodynamics of the
      transferrin-transferrin receptor system at physiological pH. GENERAL
      SIGNIFICANCE: The interaction of the iron-loaded transferrin with the transferrin
      receptor is a key cellular process that occurs during the normal course of iron
      metabolism. Understanding the thermodynamics of this interaction is important for
      iron homeostasis since the physiological requirement of iron must be
      appropriately maintained to avoid iron-related diseases. MAJOR CONCLUSIONS: The
      thermodynamic data revealed stoichiometric binding of all tested metal ions to
      transferrin with very high affinities ranging between 10(17) and 10(22)M(-1).
      Iron-loaded transferrin (monoferric or diferric) is shown to bind avidly (K~10(7)
      10(8)M(-1)) to the receptor at neutral pH with a stoichiometry of one Tf molecule
      per TfR monomer. Significantly, both the N- and the C-lobe contribute to the
      binding interaction which is shown to be both enthalpically and entropically
      driven. This article is part of a Special Issue entitled Transferrins: Molecular
      mechanisms of iron transport and disorders.

PMID- 21843603
TI  - Epigenetic mechanisms of amyloid-beta production in anisomycin-treated SH-SY5Y
      cells.
AB  - Oxidative stress and inflammation as the pathological components of Alzheimer's
      disease (AD) have been well understood. Among a diversity of mitogen-activated
      protein kinase (MAPK) family members, JNK and p38 MAPK subfamilies are relevant
      to the response of environmental stress, inflammatory stimuli, or other insults.
      Recent studies have demonstrated that epigenetic mechanisms may play a pivotal
      role in AD pathogenesis and development. In the present study, we have
      investigated epigenetic mechanisms such as DNA methylation and histone
      acetylation involved in the activation of stress-related signaling pathways for
      amyloid-beta (Abeta) production. Human neuroblastoma SH-SY5Y cells were treated
      by anisomycin, an activator of stress-related MAPKs (JNK and p38 MAPK). A
      significant increase of intracellular Abeta level in anisomycin-treated SH-SY5Y
      cells was observed. The expression of amyloid-beta precursor protein (APP), beta
      site APP-cleaving enzyme 1 (BACE1), and presenilin 1 (PS1) was upregulated by
      demethylation in three gene promoters associated with the reduction of
      methyltransferases (DNMTs). Meanwhile, an enhanced level of global histone H3
      acetylation accompanied with upregulation of histone acetyltransferases p300/CREB
      binding protein (CBP) and downregulation of histone deacetylases (HDACs) was also
      observed. These findings indicated that the activation of stress-related
      signaling pathways could result in the increased transcription of APP, BACE1, and
      PS1 genes through DNMT-dependent hypomethylation and histone H3 hyperacetylation,
      thus leading to Abeta overproduction. Moreover, our findings provided a novel
      insight into epigenetic mechanisms by which oxidative stress contributes to the
      pathogenesis of AD.

PMID- 21843604
TI  - Spatial and temporal expression patterns of nicotinic acetylcholine alpha9 and
      alpha10 subunits in the embryonic and early postnatal inner ear.
AB  - The expression and function of nicotinic receptor subunits (nAChRs) in the inner
      ear before the onset of hearing is not well understood. We investigated the mRNA
      expression of the alpha9 and alpha10 nAChR subunits in sensory hair cells of the
      embryonic and postnatal rat inner ear. We mapped their spatial and temporal
      expression in cochlear and vestibular hair cells using qPCR, [35S] labeled cRNA
      in situ hybridization, and alpha-bungarotoxin (alpha-Bgt) to label the
      presumptive membrane-bound receptor on cochlear hair cells. The results suggest
      that (1) the mRNA expression of the alpha9 subunit precedes expression of the
      alpha10 subunit in both cochlear and vestibular hair cells, (2) the mRNA
      expression of both the alpha9 and alpha10 subunits occurs earlier in the
      vestibular system than in the cochlea, (3) the mRNA expression of both subunits
      is required for the assembled receptor complexes, and (4) the presumptive
      assembled receptor, at least in the cochlea, is associated with synapse formation
      and the onset of function.

PMID- 21843605
TI  - Differential effect of amyloid beta on the cytochrome P450 epoxygenase activity
      in rat brain.
AB  - One of the prominent features of Alzheimer's disease is the excessive
      accumulation of the protein amyloid beta (Abeta) in certain areas of the brain
      leading to neurodegeneration. Abeta is cytotoxic and disrupts several
      cytoprotective pathways. Recent literature has demonstrated that certain
      cytochrome P450 (CYP) products are neuroprotective, including epoxide metabolites
      of arachidonic acid (AA), epoxyeicosatrienoic acids (EETs). The action of Abeta
      with respect to regionally produced EETs in the brain has yet to be defined.
      Epoxygenases metabolize AA into four regioisomers of EETs (14,15-, 11,12-, 8,9-
      and 5,6-EET). EETs are rapidly degraded into dihydroxyeicosatrienoic acids
      (DiHETEs) by soluble epoxide hydrolase (sEH). To determine the effect of Abeta on
      the epoxygenase activity in different regions of the brain, microsomes were
      prepared from the cerebrum and cerebellum of adult Sprague-Dawley rats and
      incubated with 1 and 10 MUM Abeta for 30 min after which epoxygenase activity
      assay was performed. Mass spectrometry indicated that incubation with Abeta
      reduced 14,15-EET production by 30% as compared to vehicle in the cerebrum, but
      not in the cerebellum. When we separated the cerebrum into cortex and
      hippocampus, significant decrease in the production of total EETs and DiHETEs
      were seen in presence of Abeta (81% and 74%) in the cortex. Moreover, 11,12-EET
      production was decreased to ~70% of vehicle in both cortex and hippocampus.
      Epoxygenase activity in the cultured astrocytes and neurons also showed reduction
      in total EET and DiHETE production (to 80% and ~70% of vehicle respectively) in
      presence of Abeta. Altogether, our data suggest that Abeta reduces epoxygenase
      activity differentially in a region-specific and cell-specific manner. The
      reduction of cytoprotective EETs by Abeta in the cerebrum may make it more prone
      to degeneration than the cerebellum. Further understanding of these interactions
      will improve our ability to protect against the pathology of Alzheimer's disease.

PMID- 21843606
TI  - MNU-induced mammary gland carcinogenesis: chemopreventive and therapeutic effects
      of vitamin D and Seocalcitol on selected regulatory vitamin D receptor pathways.
AB  - The effects of administration of vitamin D3 and Seocalcitol on MNU-induced
      carcinogenesis of mammary gland in Sprague-Dawley rats have been investigated.
      Administration of both substances in a weekly dose of 7 MUg/kg caused prolonged
      latency of mammary gland tumors. The latency of tumors was markedly prolonged for
      30-40 days by Seocalcitol. Using PET analysis, reduction in [18F]2-fluoro-2-deoxy
      d-glucose (FDG) uptake or tumor volume in tumors chemopreventively treated with
      vitamin D3 were detected in MNU-induced tumors, vitamin D3 reduced expression of
      25-hydroxylase (25OHase) (p<0.01) and 24-hydroxylase (24OHase) (p<0.01) and
      Seocalcitol 24OHase. Positive regulation of 25OHase mRNA level after the
      treatment with vitamin D3 was observed in liver, while in kidney, vitamin D3 and
      Seocalcitol induced expression of 24OHase was significant. Our observations
      indicate a cross talk between respective pathways of VDR, RARs/RXRs, TRs and ERs
      in carcinogenesis process.

PMID- 21843607
TI  - Influence of formulation variables in transdermal drug delivery system containing
      zolmitriptan.
AB  - The effects of different formulation variables including pressure sensitive
      adhesive (PSA), thickness of the matrix, solvent system, inclusion of
      crystallization inhibitor, loading amount of drug and enhancers on the
      transdermal absorption of zolmitriptan were investigated. Acrylic adhesive with
      hydroxyl functional group provided good adhesion force and high flux of
      zolmitriptan. Pseudopolymorphs of zolmitriptan were found to possess different
      solid-state properties that affected the permeation rate. Polyoxyethylene alkyl
      ethers significantly increased the permeation of zolmitriptan through hairless
      mouse skin. However, these enhancers induced crystallization of zolmitriptan.
      Kollidon((r)) 30 delayed the crystallization without altering the permeation
      profile of zolmitriptan. Stability studies suggested that terpenes did not induce
      crystallization of zolmitriptan in the patch and stable formulations could be
      produced by using cineole and limonene, or their combination.

PMID- 21843608
TI  - Bioavailability of nevirapine in rats after oral and subcutaneous administration,
      in vivo absorption from gastrointestinal segments and effect of bile on its
      absorption from duodenum.
AB  - Nevirapine is a non-nucleoside reverse transcriptase inhibitor of human
      immunodeficiency virus type-1. The usual dosing regimen is 200 mg twice/day.
      Reducing the dosing frequency would significantly improve treatment adherence and
      quality of life of patients. To study new forms of administration, it is
      necessary to do pre-clinical studies and know the absorption characteristics of
      nevirapine in laboratory animals. However, there are no studies about its
      bioavailability in rats and hardly any about its pharmacokinetic. The objectives
      of this study were to describe the pharmacokinetics of nevirapine in rats after
      intravenous, oral and subcutaneous administration, to assess its absorption by
      different regions of the gastrointestinal tract and to evaluate the effect of
      bile on its intestinal absorption. Nevirapine was well absorbed after oral and
      subcutaneous administration and the bioavailability estimated in rats (91% for
      both administration routes) was practically equal to that reported in humans (91
      93%) after oral administration of therapeutic doses. Nevirapine was absorbed from
      the duodenum, ileum and colon, while absorption from the stomach was very low.
      The rate of absorption was in the order: duodenum>ileum>colon>stomach. The
      presence of bile in the duodenum increased the absorption rate of nevirapine.

PMID- 21843609
TI  - Investigating the effect of solubility and density gradients on local
      hydrodynamics and drug dissolution in the USP 4 dissolution apparatus.
AB  - The aim of this investigation was to evaluate the effect of solubility and
      related solution density gradients, on hydrodynamics and dissolution rate in a
      low velocity pulsing flow, in the USP 4 flow-through dissolution apparatus. The
      paddle apparatus, flow-through apparatus and a free convection system were used
      in dissolution testing, using benzoic acid (BA) and lactose monohydrate (LM),
      representing slightly and freely soluble model compounds, respectively. A flow
      rate of 8 ml min(-1) (22.6 mm diameter cell) was used in the flow-through
      apparatus. Computational fluid dynamics (CFD) simulations were used to analyze
      the effect of the dissolved compounds on local hydrodynamics. A higher
      dissolution rate of both BA and LM was obtained in the free convection system
      compared to the flow-through apparatus, with highest dissolution rate from both
      compounds in the paddle apparatus. The effect of downward flow arising from
      natural convection had a significant effect for the more soluble compound, LM, on
      local fluid velocities, whereas flow reversal induced by the forced convection
      environment was a significant feature impacting on the hydrodynamics in the BA
      species transfer simulation. The effect of solution density on local
      hydrodynamics needs to be considered when selecting dissolution conditions in the
      USP 4 dissolution apparatus.

PMID- 21843610
TI  - Distinct transduction modes of arginine-rich cell-penetrating peptides for cargo
      delivery into tumor cells.
AB  - The application of cell-penetrating peptides (CPPs) for delivering various cargo
      molecules with biological functions into cells has gained much attention in
      recent years. However, the internalization mechanisms and delivery properties of
      CPP-cargo remains controversial. In this study, low- and high-molecular-weight
      cargoes attached to arginine-rich CPPs were employed: the former was the
      fluorescein isothiocyanate-labeled nona-arginine (CPP-FITC), and the latter was
      the fluorescently labeled nona-arginine-avidin complex (CPP-avidin). We measured
      the intracellular trafficking of CPP-FITC and CPP-avidin in four cancer cell
      lines in a series of microenvironments altered by the presence or absence of
      serum, different temperatures and different incubation times. The results
      revealed that CPP-cargo delivery exhibited no specificity toward any cell line,
      but the levels were found to be related to cell type and cargo. Furthermore,
      their endocytic mechanisms were investigated via incubation with related
      endocytic inhibitors. Two different types of CPP-cargo were required to cross the
      plasma membrane to bind to cell surface-associated heparan sulfate proteoglycans
      in a time-dependent manner. CPPs and small cargoes attached to CPP may enter
      cells rapidly via direct translocation in addition to the endocytic route.
      Translocation of large components linked to CPP tended to be mediated by
      macropinocytosis in an energy-dependent manner with slower rates for larger
      compounds. In contrast, the clathrin-dependent pathway is not essential to the
      translocation of either type of CPP-cargo.

PMID- 21843611
TI  - Predicting the human in vivo performance of different oral capsule shell types
      using a novel in vitro dynamic gastric model.
AB  - The disintegration of a capsule shell may determine the onset of drug dissolution
      from capsule formulations. In this study, the release of a rapidly dissolving
      model drug (paracetamol), from two hydroxypropyl methylcellulose capsules
      containing either carageenan (HPMC-C) or gellan gum (HPMC-G) and one hard gelatin
      (HG) capsule, were investigated using a conventional in vitro model, the USP
      dissolution apparatus I, and a novel in vitro model of the human gastric
      compartment, the dynamic gastric model (DGM). The results obtained in vitro were
      compared with in vivo gamma scintigraphy human data and in vivo gastric emptying
      profiles available in the literature. The drug release from HPMC-G capsules,
      observed with the USP dissolution apparatus I, was delayed with respect to the
      other two capsules, while the results obtained from the DGM in the fasted state
      were closer together, which was in agreement with data from the in vivo studies.
      In the fasted state, the capsule rupture times obtained from the DGM were similar
      to those observed by gamma scintigraphy in vivo studies. In the fed state, the
      'apparent' rupture times observed with the DGM were delayed compared to fasted,
      and were even longer than those observed by scintigraphy in vivo for HPMC-G and
      HG capsules. However, these discrepancies can reasonably be explained by
      considering the impact of food upon dispersion of the capsule contents and the
      sampling from the DGM, when compared to the human scintigraphy experiments.

PMID- 21843612
TI  - Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and
      nanomatrix for oral administration to rat.
AB  - Sorafenib is slightly absorbed in the gastrointestinal tract due to its poor
      solubility in water. To improve its absorption, a novel nanoparticulate
      formulation-nanomatrix was used in the study. The nanomatrix was a system
      prepared from a porous material Sylysia((r)) 350 and a pH sensitive polymer
      Eudragit((r)). The formulations were optimized by orthogonal design (L(9)(3(4)))
      and their bioavailability were evaluated in rat, comparing to pH-sensitive
      Eudragit nanoparticles and suspension of sorafenib. In the formulations, the
      ratio of sorafenib to Eudragit((r)) S100 was found to be more important
      determinant of the sorafenib bioavailability than the ratio of sorafenib to
      Sylysia((r)) 350. As for the bioavailability, the AUC(0-36 h) of sorafenib
      nanomatrix was 13-33 times to that of sorafenib suspension, but only 16.8% to
      40.8% that of Eudragit((r)) S100 nanoparticles. This may be resulted from the
      different drug dispersion degree, release character and bioadhension activity.
      However, because all the materials used in the nanomatrix formulation are
      commonly adjuvant, safe, easy to get and cheap, above all, the nanomatrix
      formulation can solve the stability and scaling up problems in the nanoparticles,
      it had potential to develop into a product in the future.

PMID- 21843613
TI  - Novel use patterns of Salvia divinorum: unobtrusive observation using YouTubeTM.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE AND AIMS: The traditional use of the
      Hallucinogenic sage, Salvia divinorum has been of ethnopharmalogical interest for
      some time. This plant, endemic to Oaxaca Mexico and traditionally used by the
      Mazatec, is now utilized worldwide for its psychoactive effects. This use
      demonstrates a novel use pattern which is distinctly different from Mazatec use.
      This study offers a new methodology to study emerging global plant use and
      assesses the users' experience with it. The aim of this research was to develop a
      new methodology to collect and analyze archived data on the World Wide Web,
      specifically videos which depict Salvia divinorum use. METHODS: The basis of the
      methodology for this project was unobtrusive observation which allows the
      researcher to observe without influencing the event which is being observed.
      Qualitative, ethnographic data was used in conjunction with quantitative meta
      data collected by a customized web crawler programed to archive YouTubeTM data.
      RESULTS: Using this methodology enabled us to understand reported uses and the
      users' experiences as expressed on the World Wide Web. The main result of this
      research was the documentation of a distinct, novel use pattern of Salvia
      divinorum which has developed outside of Oaxaca; a use pattern which differs in a
      number of ways from traditional, Mazatec use. The majority of the YouTubeTM
      videos analyzed were found to present indications of a positive Salvia divinorum
      experience. This result highlighted the contradiction between ethnographic data
      and what is reported by the media. Finally the representation of Salvia divinorum
      on YouTubeTM (and by inference the WWW as a whole) is a growing phenomena.
      CONCLUSIONS: While anthropological and more specifically medico-anthropological
      research has, for many years, embraced the dynamics of cultures, until recently,
      ethnopharmalogical research has generally focused on 'traditional' plant use,
      failing to capture the dynamic elements of plant/human interaction and framing
      research in the past or as decontextualized largely descriptive reports. Global
      migration and urban environments formed a basis for looking at the interplay of
      continuity and change. Such cultural dynamics are exacerbated by the
      opportunities which the WWW offers.

PMID- 21843614
TI  - Meta-analysis of the effect of herbal supplement on glycemic control in type 2
      diabetes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A variety of herbs has been used in traditional
      medicine for the treatment of diabetes. However, evidence is limited regarding
      the efficacy of individual herbs for glycemic control. We performed a systematic
      review and meta-analysis to evaluate the effect of herbal supplement on glycemic
      control in type 2 diabetes. MATERIALS AND METHODS: Randomized controlled trials
      were identified through electronic searches (MEDLINE, EMBASE and Cochrane Central
      Register of Controlled Trials) up until February 2011, historical searches of
      relevant articles and personal contact with experts in the area. Studies were
      included in the meta-analysis if they were (1) randomized placebo-controlled
      trial of single herb aimed at assessing glycemic control in type 2 diabetes, (2)
      of at least 8 weeks duration, and (3) reporting HbA(1c). Treatment effect was
      estimated with mean difference in the final value of HbA(1c) and FBG between the
      treatment and the placebo groups. RESULTS: Nine randomized, placebo-controlled
      trials (n = 487 patients) were identified. Ipomoea batatas, Silybum marianum and
      Trigonella foenum-graecum significantly improved glycemic control, whereas
      Cinnamomum cassia did not. The pooled mean differences in HbA(1c) were -0.30%
      (95% CI -0.04% to -0.57%; P = 0.02), -1.92% (95% CI -0.51% to -3.32%; P = 0.008),
      and -1.13% (95% CI -0.11% to -2.14%; P = 0.03), respectively, for Ipomoea
      batatas, Silybum marianum, and Trigonella foenum-graecum. The corresponding
      values for FBG were -10.20mg/dL (95% CI -5.32 mg/dL to -15.08 mg/dL; P<0.0001)
      and -38.05 mg/dL (95% CI -9.54 mg/dL to -66.57 mg/dL; P = 0.009), respectively,
      for Ipomoea batatas and Silybum marianum. CONCLUSIONS: The current evidence
      suggests that supplementation with Ipomoea batatas, Silybum marianum, and
      Trigonella foenum-graecum may improve glycemic control in type 2 diabetes. Such
      effect was not observed with Cinnamomum cassia. Given the limitations of the
      available studies and high heterogeneity of the study results for milk thistle
      and fenugreek, further high quality, large controlled trials using standardized
      preparation are warranted to better elucidate the effects of these herbs on
      glycemic control in type 2 diabetes patients.

PMID- 21843615
TI  - Role of Ocimum basilicum L. in prevention of ischemia and reperfusion-induced
      cerebral damage, and motor dysfunctions in mice brain.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Ocimum (Lamiaceae) has a long history
      of use as culinary and medicinal herbs. Many species are used for their
      antioxidant and neuroprotective activity in various parts of the world. Ocimum
      basilicum Linn. has been used traditionally for the treatment of anxiety,
      diabetes, cardiovascular diseases, headaches, nerve pain, as anticonvulsant and
      anti-inflammatory, and used in a variety of neurodegenerative disorders. AIM OF
      THE STUDY: The present study is designed to investigate the effect of ethyl
      acetate extract of Ocimum basilicum leaves on ischemia and reperfusion-induced
      cerebral damage, and motor dysfunctions in mice. MATERIALS AND METHODS: Global
      cerebral ischemia was induced by bilateral carotid artery occlusion for 15 min
      followed by reperfusion for 24h. Cerebral infarct size was measured using
      triphenyltetrazolium chloride staining. The concentration of thiobarbituric acid
      reactive substances (TBARS) and reduced glutathione (GSH) content was determined
      by colorimetric assay. Short-term memory was evaluated using elevated plus-maze.
      Inclined beam walking was employed to assess motor coordination. Bilateral
      carotid artery occlusion followed by reperfusion produced significant increase in
      cerebral infarct size and lipid peroxidation (TBARS), and reduced GSH content,
      and impaired short-term memory and motor coordination. RESULTS: Pre-treatment
      with standardized ethyl acetate extract of Ocimum basilicum (100 and 200mg/kg,
      p.o.) markedly reduced cerebral infarct size and lipid peroxidation, restored GSH
      content, and attenuated impairment in short-term memory and motor coordination.
      CONCLUSION: The results of the study suggest that Ocimum basilicum could be
      useful clinically in the prevention of stroke.

PMID- 21843616
TI  - Bioassay-guided isolation of norviburtinal from the root of Rehmannia glutinosa,
      exhibited angiogenesis effect in zebrafish embryo model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Rehmannia glutinosa (RR) is commonly
      used as a wound-healing agent in various traditional Chinese herbal formulae;
      while angiogenesis is one of the crucial aspects in wound-healing. AIM OF THE
      STUDY: The objective of the present study was to investigate the angiogenesis
      effects of RR aqueous crude extract and its active component(s) using zebrafish
      model. MATERIALS AND METHODS: The in vivo angiogenesis effect was studied using
      transgenic TG(fli1:EGFP)(y1)/+(AB) zebrafish embryos by observing the capillary
      sprouts formation in sub-intestinal vessel (SIV) of zebrafish embryos after 72 h
      post-fertilization under fluorescence microscopy. RESULTS: Our results indicated
      that RR aqueous crude extract (250 MUg/ml) exhibited significant angiogenesis
      effect, with an increase in capillary sprouts formation in SIV. Following
      sequential solvent partition of the RR aqueous crude extract with
      dichloromethane, ethyl acetate and n-butanol successively, the dichloromethane
      fraction (DCM) was found to have the most sprouts formation in the SIV region.
      Subjected to column chromatography, DCM fraction was further fractionated into
      six sub-fractions and among these tested, the sub-fraction C2 exhibited the most
      potent angiogenesis effect. The major component, C2A, was isolated and identified
      as norviburtinal using nuclear magnetic resonance (NMR) and mass spectrometry
      (MS). The compound norviburtinal (at 50 MUg/ml) was shown to possess significant
      angiogenesis effect in zebrafish model (p < 0.001). CONCLUSIONS: Norviburtinal
      was, for the first time, found in the extract of RR and possessed novel
      angiogenesis effect. Bioassay-guided fractionation suggested that norviburtinal
      was not the only active component responsible for the angiogenesis effect of RR.

PMID- 21843617
TI  - Assessment of the antimicrobial effect of three plants used for therapy of
      community-acquired urinary tract infection in Rio Grande do Sul (Brazil).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The urinary tract infections (UTI) are among the
      infectious diseases of bacterial origin most commonly diagnosed, and may result
      in a significant mortality. The microorganisms most frequently involved in
      community-acquired infections are Escherichia coli and Klebsiella pneumoniae,
      both Gram-negative bacillus of the Enterobacteriaceae family. In southern Brazil,
      it is common the treatment of UTI using herbs and teas, a tradition inherited
      from the ancient indigenous people. Nevertheless, there is still poor scientific
      information about the action of these plants. MATERIALS AND METHODS: Tests
      included the determination of minimum inhibitory concentration (MIC) by
      microdilution method at concentrations of 5000-156.25 MUg/MUL, and evaluation of
      antimicrobial activity by agar disc diffusion method at concentrations 500-12.5
      MUg/MUL, against the microorganisms Escherichia coli and Klebsiella pneumoniae.
      RESULTS: In the tests for MIC and antimicrobial activity by disc diffusion method
      in agar, the growth of Escherichia coli and Klebsiella pneumoniae isolates were
      not inhibited by extracts from Piptochaetium montevidense, Bulbostylis capillaris
      and Juncus capillaceus employed in the study. CONCLUSIONS: Despite the popular
      use of the plants used in this study, there is no relation between the use and
      the expected antimicrobial activity. Prolonged use of these plants may worsen the
      disease and lead to kidney involvement, and in severe cases, lead to death.

PMID- 21843618
TI  - Exploring Tagetes erecta Linn flower for the elastase, hyaluronidase and MMP-1
      inhibitory activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally Tagetes erecta Linn flower is
      claimed to treat skin diseases like sores, burns, wounds, ulcers, eczema and
      several other skin ailments. The aim of the present experiment was to evaluate
      the anti-wrinkle potential of standardized flower extract of Tagetes erecta.
      MATERIALS AND METHODS: The Tagetes erecta extract and fractions were screened for
      hyaluronidase, elastase and matrix metalloproteinase (MMP-1) inhibitory activity
      compared with the activity of standard oleanolic acid. Syringic acid and beta
      amyrin were obtained from the extract and quantified through RP-HPLC. Also the
      compounds were evaluated for anti-wrinkle activity. RESULTS: The methanol extract
      showed significant ((a)P < 0.05) hyaluronidase and elastase inhibition with IC50
      of 11.70 +/- 1.79 MUg mL(-1) and 4.13 +/- 0.93 MUg mL(-1) respectively and better
      MMP-1 inhibition compared to standard oleanolic acid. The isolated compounds
      syringic acid and beta-amyrin found to inhibit enzymes comparable to oleanolic
      acid. The RP-HPLC analysis revealed that good amounts of syringic acid and beta
      amyrin (2.30%, w/w and 0.06%) are present in Tagetes erecta. CONCLUSION: Tagetes
      erecta flower showed effective inhibition of hyaluronidase, elastase and MMP-1.
      Therefore, this experiment further rationalizes the traditional uses of this
      plant, which may be useful as an anti-wrinkle agent.

PMID- 21843619
TI  - Ethyl gallate isolated from Pistacia integerrima Linn. inhibits cell adhesion
      molecules by blocking AP-1 transcription factor.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Galls from Pistacia integerrima Linn.
      (kakadshringhi) have been used as therapeutic agent for various inflammatory
      diseases in Indian system of traditional medicine. However, the active
      constituents underlying the medicinal properties of the Pistacia integerrima
      Linn. have not been thoroughly investigated yet. AIM OF THE STUDY: Deregulated
      expression of cell adhesion molecules (CAMs) on vascular endothelium aggravates
      the inflammatory condition in various chronic diseases. In this work, we aimed to
      identify the active constituent from leaf gall of Pistacia integerrima Linn.
      using CAMs expression assay in activity guided purification, followed by
      determining the molecular mechanism of action. MATERIAL AND METHODS: Cell based
      ELISA for LPS induced CAMs expression in human vein endothelial cells (HUVECs)
      was used for the activity guided isolation form Pistacia galls followed by
      structural determination of active constituent using IR, MS and NMR spectroscopy.
      Mechanism of action of the active constituent was investigated by western blot,
      RT-PCR and EMSA experiments. RESULTS: In our study, ethyl gallate (EG) was
      identified as the active constituent of Pistacia integerrima Linn. for mediating
      its anti-inflammatory activity. It significantly attenuated LPS induced ICAM-1
      and VCAM-1 at the protein and mRNA levels. At a functional level, it inhibited
      the adhesion of neutrophils to LPS activated endothelium. To identify its
      mechanism of action, we demonstrated that EG inhibited LPS induced cell adhesion
      molecules expression by blocking AP-1 transcription factor without affecting
      nuclear transcription factor-kappaB (NF-kappaB). CONCLUSION: Our results suggest
      that EG could be useful as a lead molecule for developing therapeutic agent for
      various inflammatory diseases.

PMID- 21843621
TI  - Nepeta cataria L. var. citriodora (Becker) increases penile erection in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Nepeta cataria (NC), catnip, induces pleasure in
      cats and humans. AIM OF THE STUDY: Because sexual behavior is involved in
      pleasure, the effect of NC on sexual behavior and penile erection was evaluated
      in male rats that were acutely fed chow enriched with 10% NC leaves. Further,
      yawning was monitored because we previously demonstrated that NC modifies
      dopaminergic-related behaviors and that sexual behavior is closely linked with
      the dopaminergic system. The general activity and the motor coordination were
      examined to investigate the possible motor and emotional interferences of the
      sexual performance. MATERIAL AND METHODS: Male rats of the NC group received for
      a 4h period the chow enriched with 10% NC leaves while the control groups
      received regular chow. Fifteen min after the end of the 4h period of NC feeding
      the sexual behavior, apomorphine-induced penile erection and motor coordination
      were observed; the general activity in the open field was assessed 0, 15, 30 and
      60 min after treatment. RESULTS: NC treatment increased male rat's penile
      erection. A slightly facilitation on male rat sexual behavior and a decreased in
      general activity of NC treated rats were observed. No effects on motor
      coordination and yawning episodes were detected by the NC treatment. CONCLUSIONS:
      It was suggested that NC increases penile erection and slightly improves male rat
      sexual behavior by an action on dopaminergic systems.

PMID- 21843620
TI  - (+)-Nootkatone and (+)-valencene from rhizomes of Cyperus rotundus increase
      survival rates in septic mice due to heme oxygenase-1 induction.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Cyperus rotundus have been used
      as traditional folk medicine for the treatment of inflammatory diseases. However,
      the mechanism by which extract of rhizomes of Cyperus rotundus (ECR) elicits anti
      inflammation has not been extensively investigated so far. The aim of the present
      study was to test whether heme oxygenase (HO)-1 induction is involved in the anti
      inflammatory action of ECR. MATERIALS AND METHODS: Induction of HO-1 and
      inhibition of inducible nitric oxide synthase (iNOS)/NO production by ECR and its
      12 constituents (3 monoterpenes, 5 sesquiterpenes, and 4 aromatic compounds) were
      investigated using RAW264.7 cells in vitro. In addition, anti-inflammatory action
      of ECR and its two active ingredients (nookkatone, valencene) were confirmed in
      sepsis animal model in vivo. RESULTS: ECR increased HO-1 expression in a
      concentration-dependent manner, which was correlated with significant inhibition
      of iNOS/NO production in LPS-activated RAW264.7 cells. Among 12 compounds
      isolated from ECR, mostly sesquiterpenes induced stronger HO-1 expression than
      monoterpenes in macrophage cells. Nootkatone and valencene (sesquiterpenes)
      significantly inhibited iNOS expression and NO production in LPS-simulated
      RAW264.7 cells. Inhibition of iNOS expression by nootkatone, valencene, and ECR
      were significantly reduced in siHO-1 RNA transfected cells. Furthermore, all
      three showed marked inhibition of high mobility group box-1 (HMGB1) in LPS
      activated macrophages and increased survival rates in cecal ligation and puncture
      (CLP)-induced sepsis in mice. CONCLUSIONS: Taken together, we concluded that
      possible anti-inflammatory mechanism of ECR is, at least, due to HO-1 induction,
      in which sesquiterpenes such as nootkatone and valencene play a crucial role.

PMID- 21843622
TI  - Phytochemical analysis, antioxidant and anti-inflammatory activities of
      Phyllanthus simplex.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus simplex (Family: Euphorbiacae) is
      widely used in traditional medicines for treatment of various diseases including
      inflammation. MATERIALS AND METHODS: Petroleum ether extract (PSPE) and ethanol
      extract (PSEE) of the whole plant of Phyllanthus simplex were characterized for
      their total phenolics, tannins and flavonoids content. These extracts were
      standardized by HPTLC using phyllanthin and gallic acid respectively as markers.
      Antioxidant activity of extracts was evaluated by the DPPH, hydroxyl and
      superoxide radicals scavenging assay. The total antioxidant capacity of extracts
      was determined. Anti-inflammatory activity was evaluated by their effect on
      nitric oxide (NO) production in isolated rat peritoneal macrophages; carragennan
      induced paw edema and formation of cotton pellet-induced granuloma in rats.
      RESULTS: Abundance of phenolics was found in PSEE. Phyllanthin and gallic acid
      content in PSPE and PSEE were found to be 14.5 and 0.65% (w/w) respectively. PSEE
      showed concentration dependent significant scavenging of DPPH, hydroxyl and
      superoxide radicals with IC(50) values 102.219, 171.485 and 24.73 MUg/ml
      respectively. PSEE significantly inhibited NO production in isolated rat
      peritoneum macrophages. Moreover, it also exhibited significant inhibition of
      carragennan-induced paw edema (58.48 +/- 0.028%, p < 0.001, at 6h, 200 mg/kg oral
      dose) and cotton pellet-induced granuloma formation (45.671 +/- 0.712%, p <
      0.001, at 200mg/kg oral dose). Anti-inflammatory activity of PSEE was found to be
      comparable to diclofenac sodium. CONCLUSIONS: Significant antioxidant and anti
      inflammatory activities were found in PSEE which may be attributed to its high
      phenolic content.

PMID- 21843623
TI  - Antiproliferative activity and standardization of Tecomella undulata bark extract
      on K562 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Tecomella undulata is primarily used
      in the treatment of syphilis, painful swellings and cancer by traditional
      healers. Also, it is claimed to be useful in treating urinary discharges,
      enlargement of spleen, leucorrhoea, leukoderma, tumors, liver disorders,
      gonorrhea, gout and promotes wound healing in Indian traditional system of
      medicine. AIM: To establish a scientific validation for the antitumor effects of
      Tecomella undulata bark and explore the mechanistic pathway in chronic myeloid
      leukemia cell line, K562. The study was further extended to standardize the
      extract using quercetin as biomarker. METHODS: Induction of apoptosis by
      chloroform extract of Tecomella undulata bark (CTUB) was determined by MTT,
      Annexin V and caspase activation assays. The cell cycle analysis was done by flow
      cytometer and nuclear staining by DAPI. The standardization of the extract was
      performed through reverse phase-HPLC method under PDA detection. RESULT: Results
      clearly showed the induction of apoptosis by CTUB in K562 cells. The effect was
      found to be dose dependent, having IC(50) of 30 MUg/ml with activation of FAS,
      FADD, caspase 8, caspase 3/7 and fragmentation of DNA. The bioactive CTUB was
      determined to possess 0.03% (w/w) of quercetin. CONCLUSION: The investigation
      clearly demonstrated the potential antitumor effect of CTUB, thereby validating
      the traditional claim. Quercetin, known to have anticancer activity is being
      reported and quantified for the first time from the bark of Tecomella undulata.

PMID- 21843624
TI  - Direct inhibition of calcineurin by caffeoyl phenylethanoid glycosides from
      Teucrium chamaedrys and Nepeta cataria.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Teucrium chamaedrys L. and Nepeta cataria L.
      (Lamiaceae) are species with traditional uses that relate to the treatment of
      inflammation. Extracts of both species were found to inhibit calcineurin; an
      important regulator of T-cell mediated inflammation that has received little
      attention in ethnopharmacological research. MATERIALS AND METHODS: Extracts and
      isolated compounds were tested against calcineurin in its calmodulin-activated
      and basal un-activated state. Active compounds were isolated using Sephadex LH-20
      gel filtration and HPLC then identified using NMR spectroscopy. RESULTS AND
      CONCLUSIONS: Activity-guided fractionation of Teucrium chamaedrys and Nepeta
      cataria led to the isolation of the caffeoyl phenylethanoid glycosides
      teucrioside, verbascoside and lamiuside A (teupolioside). The three compounds
      inhibited calcineurin both in the presence and absence of calmodulin, suggesting
      a direct interaction with calcineurin. Calcineurin inhibition should be
      considered as a potential mode of action when investigating the immunomodulatory
      activity of caffeoyl phenylethanoid glycoside containing plants.

PMID- 21843625
TI  - Recovery and purification of plant-made recombinant proteins.
AB  - Plants are becoming commercially acceptable for recombinant protein production
      for human therapeutics, vaccine antigens, industrial enzymes, and nutraceuticals.
      Recently, significant advances in expression, protein glycosylation, and gene-to
      product development time have been achieved. Safety and regulatory concerns for
      open-field production systems have also been addressed by using contained systems
      to grow transgenic plants. However, using contained systems eliminates several
      advantages of open-field production, such as inexpensive upstream production and
      scale-up costs. Upstream technological achievements have not been matched by
      downstream processing advancements. In the past 10 years, the most research
      progress was achieved in the areas of extraction and pretreatment. Extraction
      conditions have been optimized for numerous proteins on a case-by-case basis
      leading to the development of platform-dependent approaches. Pretreatment
      advances were made after realizing that plant extracts and homogenates have
      unique compositions that require distinct conditioning prior to purification.
      However, scientists have relied on purification methods developed for other
      protein production hosts with modest investments in developing novel plant
      purification tools. Recently, non-chromatographic purification methods, such as
      aqueous two-phase partitioning and membrane filtration, have been evaluated as
      low-cost purification alternatives to packed-bed adsorption. This paper reviews
      seed, leafy, and bioreactor-based platforms, highlights strategies for the
      primary recovery and purification of recombinant proteins, and compares process
      economics between systems. Lastly, the future direction and research needs for
      developing economically competitive recombinant proteins with commercial
      potential are discussed.

PMID- 21843626
TI  - Production of foreign proteins using plastid transformation.
AB  - In the past decades, the progress made in plant biotechnology has made possible
      the use of plants as a novel production platform for a wide range of molecules.
      In this context, the transformation of the plastid genome has given a huge boost
      to prove that plants are a promising system to produce recombinant proteins. In
      this review, we provide a background on plastid genetics and on the principles of
      this technology in higher plants. Further, we discuss the most recent
      biotechnological applications of plastid transformation for the production of
      enzymes, therapeutic proteins, antibiotics, and proteins with immunological
      properties. We also discuss the potential of plastid biotechnology and the novel
      tools developed to overcome some limitations of chloroplast transformation.

PMID- 21843627
TI  - Delivery of plant-made vaccines and therapeutics.
AB  - As commercial approval of the first, purified, plant-based biopharmaceuticals for
      parenteral delivery to humans approaches, improved strategies for delivery of
      plant-made vaccines and therapeutics are required to ensure their further
      development and to fulfil the prospect of supplying a global solution for
      affordable medicines. To ensure that this occurs, research should investigate and
      characterise the host immune system in addition to the effects of adjuvants and
      carrier vehicles on consistency and efficacy of vaccination. In this review we
      explore the basic understandings of pharmaceutical delivery and its effect on
      immunogenicity in an effort to advance the plant-made pharmaceutical platform.

PMID- 21843629
TI  - Staphylococcus aureus inhibits nuclear factor kappa B activation mediated by
      prolactin in bovine mammary epithelial cells.
AB  - The hormone prolactin (PRL) regulates differentiation and lactation in the bovine
      mammary epithelium. This tissue is especially prone to contracting mastitis, a
      disease characterized by an inflammatory response in the mammary gland.
      Staphylococcus aureus is the infectious agent primarily responsible for mastitis.
      In a previous study, we have shown that bovine PRL (bPRL) stimulates S. aureus
      internalization in bovine mammary epithelial cells (bMECs) by regulating several
      host innate immune elements, which are often modulated by nuclear factor kappa B
      (NF-kappaB). However, it is unknown whether the activation of the NF-kappaB
      transcription factor is regulated by bPRL during S. aureus internalization. The
      objective of this study was to determine the role of NF-kappaB in bPRL-stimulated
      bMECs during S. aureus internalization. Our results showed that bPRL (5 ng/ml)
      induced NF-kappaB activation in bMECs; however, it was inhibited by S. aureus in
      presence of the hormone. When we blocked NF-kappaB activation with
      acetylsalicylic acid, we detected an inhibition in S. aureus internalization
      (48%) in bPRL-stimulated bMECs. The infection-induced inhibition of NF-kappaB
      activation in the presence of bPRL correlates with the downregulation in bPRL
      mediated tumor necrosis factor (TNF)-alpha (27%) and tracheal antimicrobial
      peptide (TAP, 70%) mRNA expression and nitric oxide (NO) production in bMECs. We
      also detected an inhibition in the expression of the bPRL target gene kappa
      casein (50%) under these conditions. Interestingly, these effects are not
      achieved through increased PRL receptor expression (PRLR), as it was inhibited
      (48%) compared to control cells. In conclusion, NF-kappaB activation in bMECs is
      inhibited by S. aureus in the presence of bPRL, suggesting a mechanism by which
      the host innate immune response may be compromised during subclinical mastitis.

PMID- 21843628
TI  - Adenylate cyclase activity of Pseudomonas aeruginosa ExoY can mediate bleb-niche
      formation in epithelial cells and contributes to virulence.
AB  - We previously showed that ADP-ribosylation (ADP-r) activity of ExoS, a type III
      secreted toxin of Pseudomonas aeruginosa, enables bacterial replication in
      corneal and respiratory epithelial cells and correlates with bacterial
      trafficking to plasma membrane blebs (bleb-niche formation). Here, we explored
      another type III secreted toxin, ExoY, for its impact on intracellular
      trafficking and survival, and for virulence in vivo using a murine corneal
      infection model. Chromosomal or plasmid-mediated expression of exoY in invasive
      P. aeruginosa (strain PAO1) enabled bacteria to form and traffic to epithelial
      membrane blebs in the absence of other known effectors. In contrast, plasmid
      expression of any of four adenylate cyclase mutant forms of exoY did not enable
      bleb-niche formation, and bacteria localized to perinuclear vacuoles as for
      effector-null mutant controls. None of the plasmid-complemented bacteria used in
      this study showed ADP-r activity in the absence of ExoS and ExoT. In contrast to
      ADP-r activity of ExoS, bleb-niche formation induced by ExoY's adenylate cyclase
      activity was not accompanied by enhanced intracellular replication. In vivo
      results showed that ExoY-adenylate cyclase activity promoted P. aeruginosa
      corneal virulence in susceptible mice. Together the data show that adenylate
      cyclase activity of P. aeruginosa ExoY, similarly to the ADP-r activity of ExoS,
      can mediate bleb-niche formation in epithelial cells. While this activity did not
      promote intracellular replication in vitro, ExoY conferred increased virulence in
      vivo in susceptible mice. Mechanisms for bleb-niche formation and relationships
      to intracellular replication and virulence in vivo require further investigation
      for both ExoS and ExoY.

PMID- 21843631
TI  - New insights into autoantibody profiles from immune privileged sites in the eye:
      a glaucoma study.
AB  - Glaucoma is a chronic neurodegenerative disease and one of the leading causes of
      blindness. Autoantibody based immune processes are assumed to be involved in its
      pathogenesis. However, it is still unclear to what extent autoantibody patterns
      found in the eye (aqueous humor) are congruent to systemic autoantibodies
      (blood). Consistency would underline the specificity of known serum antibody
      markers for glaucoma. In this study we used antigen microarrays to analyze
      autoantibody reactivities in sera and corresponding aqueous humor samples of
      primary open-angle glaucoma patients (N=37) and non-glaucomatous controls (N=31).
      Compared to control subjects several divergent immunoreactivities were identified
      for the glaucoma group in both body fluids. Interestingly, 20% of the tested
      antigens revealed increased immunoreactivities (e.g., against HSP27, MBP, and
      alpha-1-antitrypsin) and 7.5% decreased immunoreactivities (e.g., against GFAP
      and beta-L-crystallin), thus demonstrating a significant alteration of the
      autoantibody profiles in glaucoma patients. Using an artificial neural network in
      combination with a unique serum autoantibody pattern on prospective sera we were
      able to detect glaucoma with a specificity and sensitivity of approximately 93%.
      The intraindividual comparison revealed a strong correlation of detected
      immunoreactivities in sera and comparative aqueous humor samples in both study
      groups. These results emphasize the specificity of immunoreactions found in blood
      samples of glaucoma patients. Furthermore they indicate the necessity of
      analyzing not only up-regulated but also down-regulated antibody reactivities,
      which might be likewise relevant for the understanding of other diseases.

PMID- 21843630
TI  - C-reactive protein is related to memory and medial temporal brain volume in older
      adults.
AB  - Recent research suggests a central role for inflammatory mechanisms in cognitive
      decline that may occur prior to evidence of neurodegeneration. Limited
      information exists, however, regarding the relationship between low-grade
      inflammation and cognitive function in healthy older adults. This study examined
      the relation between inflammation, verbal memory consolidation, and medial
      temporal lobe volumes in a cohort of older community-dwelling subjects. Subjects
      included 141 functionally intact, community-dwelling older adults with detectable
      (n=76) and undetectable (n=65) levels of C-reactive protein. A verbal episodic
      memory measure was administered to all subjects, and measures of delayed recall
      and recognition memory were assessed. A semiautomated parcellation program was
      used to analyze structural MRI scans. On the episodic memory task, analysis of
      covariance revealed a significant CRP group by memory recall interaction, such
      that participants with detectable levels of CRP evidenced worse performance after
      a delay compared to those with undetectable levels of CRP. Individuals with
      detectable CRP also demonstrated lower performance on a measure of recognition
      memory. Imaging data demonstrated smaller left medial temporal lobe volumes in
      the detectable CRP group as compared with the undetectable CRP group. These
      findings underscore a potential role for inflammation in cognitive aging as a
      modifiable risk factor.

PMID- 21843632
TI  - Tat-enhanced delivery of metallothionein can partially prevent the development of
      diabetes.
AB  - Metallothioneins (MTs) are intracellular low-molecular-weight, cysteine-rich
      proteins with potent metal-binding and redox functions, but with limited membrane
      permeativity. The aim of this study was to investigate whether we could enhance
      delivery of MT-1 to pancreatic islets or beta cells in vitro and in vivo. The
      second goal was to determine whether increased MT-1 could prevent cellular
      toxicity induced by high glucose and free fatty acids in vitro
      (glucolipotoxicity) and ameliorate the development of diabetes induced by
      streptozotocin in mice or delay the development of diabetes by improving insulin
      secretion and resistance in the OLETF rat model of type 2 diabetes. Expression of
      HIV-1 Tat-MT-1 enabled efficient delivery of MT into both INS-1 cells and rat
      islets. Intracellular MT activity increased in parallel with the amount of
      protein delivered to cells. The formation of reactive oxygen species,
      glucolipotoxicity, and DNA fragmentation due to streptozotocin decreased after
      treating pancreatic beta cells with Tat-MT in vitro. Importantly, in vivo,
      intraperitoneal injection resulted in delivery of the Tat-MT protein to the
      pancreas as well as liver, muscle, and white adipose tissues. Multiple injections
      increased radical-scavenging activity, decreased apoptosis, and reduced
      endoplasmic reticulum stress in the pancreas. Treatment with Tat-MT fusion
      protein delayed the development of diabetes in streptozotocin-induced mice and
      improved insulin secretion and resistance in OLETF rats. These results suggest
      that in vivo transduction of Tat-MT may offer a new strategy to protect
      pancreatic beta cells from glucolipotoxicity, may improve insulin resistance in
      type 2 diabetes, and may have a protective effect in preventing islet destruction
      in type 1 diabetes.

PMID- 21843633
TI  - alpha-tocopherol and alpha-tocopheryl phosphate interact with the cannabinoid
      system in the rodent hippocampus.
AB  - alpha-Tocopherol (alpha-TOH), a dietary component of vitamin E, is well known for
      its antioxidant capacity. Nevertheless, recent studies have pointed out non-anti
      radical properties including cellular and genomic actions. Decreased levels of
      alpha-tocopherol in the brain are associated with neuronal dysfunctions ranging
      from mood disorders to neurodegeneration. All these behavioral effects of alpha
      tocopherol deficiency probably do not rely simply on its anti-radical properties,
      but could also be reminiscent of a not-yet characterized neuromodulatory action.
      We have thus measured the direct actions of alpha-tocopherol and of its natural
      phosphate derivative, alpha-tocopheryl phosphate (alpha-TP), on synaptic
      transmission in rodent hippocampus. These compounds had opposite actions on both
      glutamatergic and GABAergic transmission: whereas alpha-TOH potentiated these
      transmissions, alpha-TP inhibited them. Interestingly, these effects were both
      mediated by cannabinoid receptors (CB1Rs), because they were blocked by the CB1R
      antagonist AM251. Although alpha-tocopherol and alpha-tocopheryl phosphate did
      not directly bind CB1R, both alpha-TP and CB1R agonists inhibited forskolin
      evoked Erk1/2 phosphorylation in a nonadditive manner. Furthermore, both alpha
      tocopherol and alpha-tocopheryl phosphate attenuated depolarization-induced
      suppression of excitation and CB1R agonist-mediated hypothermia. Therefore, we
      identify alpha-tocopherol as new lipid modulator of the cannabinoid system in the
      rodent hippocampus, i.e., a novel "non-anti-radical" action of vitamin E, which
      may have some preeminent impact in neuronal disorders associated with vitamin E
      deficiency.

PMID- 21843634
TI  - Transcriptional modulation of the NAD(P)H:quinone oxidoreductase 1 by mercury in
      human hepatoma HepG2 cells.
AB  - NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones plays a
      critical role in cancer prevention. Heavy metals such as mercury (Hg(2+)) alter
      the carcinogenicity of aryl hydrocarbon receptor ligands, mainly by modifying
      various xenobiotic-metabolizing enzymes such as NQO1. Therefore, we examined the
      effect of Hg(2+) on the expression of NQO1 in human hepatoma HepG2 cells. For
      this purpose HepG2 cells were incubated with various concentrations of Hg(2+)
      (2.5, 5, and 10MUM) in the presence and absence of two NQO1 inducers, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and isothiocyanate sulforaphane (SUL), as
      bifunctional and monofunctional inducers, respectively. Analysis of the time
      dependent effect of Hg(2+) revealed that Hg(2+) increased the expression of NQO1
      mRNA in a time-dependent manner. In addition, Hg(2+) increased NQO1 at the mRNA,
      protein, and activity levels in the presence and absence of both NQO1 inducers,
      TCDD and SUL, which coincided with increased nuclear accumulation of Nrf2
      protein. Investigating the effect of Hg(2+) at the transcriptional level revealed
      that Hg(2+) significantly induced the antioxidant-responsive element-dependent
      luciferase reporter gene expression in the absence and the presence of both NQO1
      inducers. NQO1 mRNA and protein decay experiments revealed a lack of
      posttranscriptional and posttranslational mechanisms. Transfecting HepG2 cells
      with siRNA for Nrf2 significantly decreased the Hg(2+)-mediated induction of NQO1
      mRNA and catalytic activity by approximately 90%. In conclusion, we demonstrated
      that Hg(2+) regulates the expression of the NQO1 gene through a transcriptional
      mechanism in human hepatoma HepG2 cells. In addition, Nrf2 is involved in the
      modulation of NQO1 by Hg(2+).

PMID- 21843635
TI  - Age- and sex-related differences in the acquisition and reinstatement of ethanol
      CPP in mice.
AB  - Many people begin to experiment with alcohol during adolescence, an important
      developmental period during which sex differences in the effects of ethanol
      appear. In the present study we evaluated the effect of ethanol (0, 0.625, 1.25
      or 2.5 g/kg) on the acquisition of a conditioned place preference (CPP) in early
      and late adolescent male and female mice. In addition, we assessed the capacity
      of ethanol to induce reinstatement of the CPP after its extinction. CPP was
      induced in early and late adolescent females with 2.5 g/kg, and in early
      adolescent males with 1.25 or 2.5 g/kg of ethanol. No CPP was observed in late
      adolescent males. Priming with ethanol reinstated the CPP induced by the highest
      dose in early adolescent male and early and late adolescent female mice. Our data
      suggest that early adolescents of both sex and late adolescent females are
      particularly vulnerable to the effects of ethanol.

PMID- 21843636
TI  - Stable over-expression of PPARbeta/delta and PPARgamma to examine receptor
      signaling in human HaCaT keratinocytes.
AB  - Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) function
      and receptor cross-talk with other nuclear receptors, including PPARgamma and
      retinoic acid receptors (RARs), was examined using stable human HaCaT
      keratinocyte cell lines over-expressing PPARbeta/delta or PPARgamma. Enhanced
      ligand-induced expression of two known PPAR target genes, adipocyte
      differentiation-related protein (ADRP) and angiopoietin-like protein 4 (ANGPTL4),
      was found in HaCaT keratinocytes over-expressing PPARbeta/delta or PPARgamma.
      Over-expression of PPARbeta/delta did not modulate the effect of a PPARgamma
      agonist on up-regulation of ADRP or ANGPTL4 mRNA in HaCaT keratinocytes. All
      trans retinoic acid (atRA) increased expression of a known RAR target gene, yet
      despite a high ratio of fatty acid binding protein 5 (FABP5) to cellular retinoic
      acid binding protein II, did not increase expression of ANGPTL4 or 3
      phosphoinositide-dependent-protein kinase 1 (PDPK1), even in HaCaT keratinocytes
      expressing markedly higher levels of PPARbeta/delta. While PPARbeta/delta
      dependent attenuation of staurosporine- or UVB-induced poly (ADP-ribose)
      polymerase (PARP) cleavage was not observed, PPARbeta/delta- and PPARgamma
      dependent repression of UVB-induced expression and secretion of inflammatory
      cytokines was found in HaCaT keratinocytes over-expressing PPARbeta/delta or
      PPARgamma. These studies suggest that FABP5 does not transport atRA or GW0742 to
      PPARbeta/delta and promote anti-apoptotic activity by increasing expression of
      PDPK1, or that PPARbeta/delta interferes with PPARgamma transcriptional activity.
      However, these studies demonstrate that stable over-expression of PPARbeta/delta
      or PPARgamma significantly increases the efficacy of ligand activation and
      represses UVB-induced expression of tumor necrosis factor alpha (TNFalpha),
      interleukin 6 (IL6), or IL8 in HaCaT keratinocytes, thereby establishing an
      excellent model to study the functional role of these receptors in human
      keratinocytes.

PMID- 21843638
TI  - Stability of fast oscillations in the mammalian olfactory bulb: experiments and
      modeling.
AB  - In the rat olfactory bulb (OB), fast oscillations of the local field potential
      (LFP) are observed during the respiratory cycle. Gamma-range oscillations (40-90
      Hz) occur at the end of inspiration, followed by beta-range oscillations (15-30
      Hz) during exhalation. These oscillations are highly stereotypical, and their
      frequencies are stable under various conditions. In this study, we investigate
      the effect of stimulus intensity on activity in the OB. Using a double
      cannulation protocol, we showed that although the frequency of the LFP
      oscillation does depend on the respiratory cycle phase, it is relatively
      independent of the intensity of odorant stimulation. In contrast, we found that
      the individual firing rate of mitral OB cells dramatically changed with the
      intensity of the stimulation. This suggests that OB fast oscillation parameters,
      particularly frequency, are fully determined by intrinsic OB network parameters.
      To test this hypothesis, we explored a model of the OB where fast oscillations
      are generated by the interplay between excitatory mitral/tufted cells and
      inhibitory granule cells with graded inhibition. We found that our model has two
      distinct activity regimes depending on the amount of noise. In a low-noise
      regime, the model displays oscillation in the beta range with a stable frequency
      across a wide range of excitatory inputs. In a high-noise regime, the model
      displays oscillatory dynamics with irregular cell discharges and fast
      oscillations, similar to what is observed during gamma oscillations but without
      stability of the oscillation frequency with respect to the network external
      input. Simulations of the full model and theoretical studies of the network's
      linear response show that the characteristics of the low-noise regime are induced
      by non-linearities in the model, notably, the saturation of graded inhibition.
      Finally, we discuss how this model can account for the experimentally observed
      stability of the oscillatory regimes.

PMID- 21843637
TI  - Regulation of basal body and ciliary functions by Diversin.
AB  - The centrosome is essential for the formation of the cilia and has been
      implicated in cell polarization and signaling during early embryonic development.
      A number of Wnt pathway components were found to localize at the centrosome, but
      how this localization relates to their signaling functions is unclear. In this
      study, we assessed a role for Diversin, a putative Wnt pathway mediator, in
      developmental processes that involve cilia. We find that Diversin is specifically
      localized to the basal body compartment near the base of the cilium in Xenopus
      multi-ciliated skin cells. Overexpression of Diversin RNA disrupted basal body
      polarization in these cells, suggesting that tightly regulated control of
      Diversin levels is crucial for this process. In cells depleted of endogenous
      Diversin, basal body structure appeared abnormal and this was accompanied by
      disrupted polarity, shortened or absent cilia and defective ciliary flow. These
      results are consistent with the involvement of Diversin in processes that are
      related to the acquisition of cell polarity and require ciliary functions.

PMID- 21843639
TI  - Adaptive training session for a P300 speller brain-computer interface.
AB  - With a brain-computer interface (BCI), it is nowadays possible to achieve a
      direct pathway between the brain and computers thanks to the analysis of some
      particular brain activities. The detection of even-related potentials, like the
      P300 in the oddball paradigm exploited in P300-speller, provides a way to create
      BCIs by assigning several detected ERP to a command. Due to the noise present in
      the electroencephalographic signal, the detection of an ERP and its different
      components requires efficient signal processing and machine learning techniques.
      As a consequence, a calibration session is needed for training the models, which
      can be a drawback if its duration is too long. Although the model depends on the
      subject, the goal is to provide a reliable model for the P300 detection over
      time. In this study, we propose a new method to evaluate the optimal number of
      symbols (i.e. the number of ERP that shall be detected given a determined target
      probability) that should be spelt during the calibration process. The goal is to
      provide a usable system with a minimum calibration duration and such that it can
      automatically switch between the training and online sessions. The method allows
      to adaptively adjust the number of training symbols to each subject. The
      evaluation has been tested on data recorded on 20 healthy subjects. This
      procedure lets drastically reduced the calibration session: height symbols during
      the training session reach an initialized system with an average accuracy of 80%
      after five epochs.

PMID- 21843640
TI  - A modeling based study on the origin and nature of evoked post-synaptic local
      field potentials in granular layer.
AB  - Understanding population activities of underlying neurons reveal emergent
      behavior as patterns of information flow in neural circuits. Evoked local field
      potentials (LFPs) arise from complex interactions of spatial distribution of
      current sources, time dynamics, and spatial distribution of dipoles apart
      underlying conductive properties of the extracellular medium. We reconstructed
      LFP to test and parameterize the molecular mechanisms of cellular function with
      network properties. The sensitivity of LFP to local excitatory and inhibitory
      connections was tested using two novel techniques. In the first, we used a single
      granule neuron as a model kernel for reconstructing population activity. The
      second technique consisted using a detailed network model. LTP and LTD regulating
      the spatiotemporal pattern of granular layer responses to mossy fiber inputs was
      studied. The effect of changes in synaptic release probability and modulation in
      intrinsic excitability of granule cell on LFP was studied. The study revealed
      cellular function and plasticity were represented in LFP wave revealing the
      activity of underlying neurons. Changes to single cell properties during LTP and
      LTD were reflected in the LFP wave suggesting the sparse recoding function of
      granule neurons as spatial pattern generators. Both modeling approaches generated
      LFP in vitro (Mapelli and D'Angelo, 2007) and in vivo (Roggeri et al., 2008)
      waveforms as reported in experiments and predict that the expression mechanisms
      revealed in vitro can explain the LFP changes associated with LTP and LTD in
      vivo.

PMID- 21843641
TI  - The non-antibiotic properties of tetracyclines: clinical potential in ophthalmic
      disease.
AB  - INTRODUCTION: Beyond their decades of long use as broad-spectrum antibiotics,
      tetracyclines and their derivatives have been shown to exhibit non-antimicrobial
      properties including their ability to interact with matrix metalloproteinases
      (MMP), tissue inhibitors of MMPs, growth factors and cytokines. As such, they are
      capable of affecting inflammation, immunomodulation, cell proliferation, and
      angiogenesis. Although they have been used to treat a variety of conditions
      including acne, cutaneous sarcoid, and rheumatoid arthritis, amongst others,
      their use in treating ophthalmologic disease is in its infancy. MATERIALS AND
      METHODS: A literature review on the role of non-antimicrobial properties of
      tetracyclines, semisynthetic tetracyclines, and chemically modified non
      antibacterial tetracyclines (CMTs) and their clinical properties was performed.
      The effects of these compounds in relation to ophthalmic disease are presented.
      RESULTS: Due to their non-antimicrobial properties, tetracyclines and their
      derivatives are capable of influencing a wide variety of ocular diseases in
      animal models. By affecting expression of MMP-9 and tumor necrosis factor (TNF)
      alpha, these compounds decrease corneal permeability, improve corneal smoothness,
      and reduce meibomian gland dysfunction; this improves the tear film which in turn
      restores the optical quality of the tear film and cornea. Sterile corneal
      ulceration may be inhibited via anticollagenase activity; this has been
      demonstrated in both animal models and case reports. CMTs suppress
      cataractogenesis in a diabetic rat model, possibly by affecting MMPs. With
      respect to retinal disease, tetracyclines can inhibit both microglial-mediated
      cell death and retinal cell apoptosis as well as prevent retinal capillary damage
      via caspase inhibition thus preventing retinal neovascularization. Experimental
      choroidal neovascularization is reduced by inhibition of MMP-2 and MMP-9,
      elevation of pigment epithelial derived growth factor (PEDF), and reduction of
      vascular endothelial growth factor (VEGF) expression via Fas ligand. DISCUSSION:
      Due to their non-antimicrobial properties, tetracyclines and their derivatives
      are capable of influencing a wide variety of ocular disease in animal models.
      Research suggests that they are able to reduce inflammation in the eyelid
      meibomian glands, improve optical clarity of the cornea, retard cataract
      formation, and limit ocular angiogenesis. They may have a role in treating the
      leading causes of vision loss: cataract, age-related macular degeneration, and
      diabetic retinopathy, all of which are anticipated to increase in incidence due
      to the aging population. CONCLUSIONS: Tetracyclines, semisynthetic tetracyclines,
      and CMTs may have a role in the treatment of several important ophthalmologic
      diseases; however, further research is required, including prospective
      multicenter clinical trials.

PMID- 21843642
TI  - Recombinant production of antimicrobial peptides in Escherichia coli: a review.
AB  - Antimicrobial peptides are of great interest due to their potential application
      as novel antibiotics. Large quantities of highly purified peptides are required
      to meet the needs of basic research and clinical trials. Compared with isolation
      from natural sources and chemical synthesis, recombinant approach offers the most
      cost-effective means for large-scale peptide manufacture. Among the systems
      available for heterologous protein production, Escherichia coli has been the most
      widely used host. Antimicrobial peptides produced in E. coli are often expressed
      as fusion proteins, a strategy necessary to mask these peptides' lethal effect
      towards the host and protect them from proteolytic degradation. The present
      article reviews commonly used fusion partners (e.g., solubility-enhancing,
      aggregation-promoting and self-cleavable carriers, etc.), cleavage methods and
      optimization options for antimicrobial peptides production in E. coli. In
      addition, the various approaches developed to generate recombinant human
      antimicrobial peptide LL-37, which offer excellent examples demonstrating
      effective production strategies, were briefly discussed.

PMID- 21843643
TI  - The structure of NS-398 bound to cyclooxygenase-2.
AB  - The cyclooxygenases (COX-1 and COX-2) are membrane-associated, heme-containing
      homodimers that generate prostaglandin H(2) from arachidonic acid (AA) in the
      committed step of prostaglandin biogenesis and are the targets for nonsteroidal
      anti-inflammatory drugs (NSAIDs). N-(2-cyclohexyloxy-4-nitrophenyl)
      methanesulfonamide (NS-398) was the first in a series of isoform-selective drugs
      designed to preferentially inhibit COX-2, with the aim of ameliorating many of
      the toxic gastrointestinal side effects caused by conventional NSAID inhibition.
      We determined the X-ray crystal structure of murine COX-2 in complex with NS-398
      utilizing synchrotron radiation to 3.0A resolution. NS-398 binds in the
      cyclooxygenase channel in a conformation that is different than that observed for
      other COX-2-selective inhibitors, such as celecoxib, with no discernible
      penetration into the side pocket formed in COX-2 by the isoform-specific
      substitutions of I434V, H513R, and I523V. Instead, the methanesulfonamide moiety
      of NS-398 interacts with the side chain of Arg-120 at the opening of the
      cyclooxygenase channel, similar to that observed for acidic, nonselective NSAIDs
      such as indomethacin and flurbiprofen. Our structure validates inhibitor studies
      that identified Arg-120 as a molecular determinant for time-dependent inhibition
      of COX-2 by NS-398.

PMID- 21843644
TI  - The effect of context on the folding of beta-hairpins.
AB  - Small beta-hairpin peptides have been widely used as models for the folding of
      beta-sheets. But how applicable is the folding of such models to beta-structure
      in larger proteins with conventional hydrophobic cores? Here we present multiple
      unfolding simulations of three such proteins that contain the WW domain double
      hairpin beta-sheet motif: cold shock protein A (CspA), cold shock protein B
      (CspB) and glucose permease IIA domain. We compare the behavior of the free motif
      in solution and in the context of proteins of different size and architecture.
      Both Csp proteins lost contacts between the double-hairpin motif and the protein
      core as the first step of unfolding and proceeded to unfold with loss of the
      third beta-strand, similar to the isolated WW domain. The glucose permease IIA
      domain is a larger protein and the contacts between the motif and the core were
      not lost as quickly. Instead the unfolding pathway of glucose permease IIA
      followed a different pathway with beta1 pulling away from the sheet first.
      Interestingly, when the double hairpin motif was excised from the glucose
      permease IIA domain and simulated in isolation in water it unfolded by the same
      pathway as the WW domain, indicating that it is tertiary interactions with the
      protein that alter the motif's unfolding not a sequence dependent effect on its
      intrinsic unfolding behavior. With respect to the unfolding of the hairpins,
      there was no consistent order to the loss of hydrogen bonds between the beta
      strands in the hairpins in any of the systems. Our results show that while the
      folding behavior of the isolated WW domain is generally consistent with the
      double hairpin motif's behavior in the cold shock proteins, it is not the case
      for the glucose permease IIA domain. So, one must be cautious in extrapolating
      findings from model systems to larger more complicated proteins where tertiary
      interactions can overwhelm intrinsic behavior.

PMID- 21843645
TI  - Structural basis for the functional and inhibitory mechanisms of beta-hydroxyacyl
      acyl carrier protein dehydratase (FabZ) of Plasmodium falciparum.
AB  - The beta-hydroxyacyl-acyl carrier protein dehydratase of Plasmodium falciparum
      (PfFabZ) catalyzes the third and important reaction of the fatty acid elongation
      cycle. The crystal structure of PfFabZ is available in hexameric (active) and
      dimeric (inactive) forms. However, PfFabZ has not been crystallized with any
      bound inhibitors until now. We have designed a new condition to crystallize
      PfFabZ with its inhibitors bound in the active site, and determined the crystal
      structures of four of these complexes. This is the first report on any FabZ
      enzyme with active site inhibitors that interact directly with the catalytic
      residues. Inhibitor binding not only stabilized the substrate binding loop but
      also revealed that the substrate binding tunnel has an overall shape of "U". In
      the crystal structures, residue Phe169 located in the middle of the tunnel was
      found to be in two different conformations, open and closed. Thus, Phe169, merely
      by changing its side chain conformation, appears to be controlling the length of
      the tunnel to make it suitable for accommodating longer substrates. The volume of
      the substrate binding tunnel is determined by the sequence as well as by the
      conformation of the substrate binding loop region and varies between organisms
      for accommodating fatty acids of different chain lengths. This report on the
      crystal structures of the complexes of PfFabZ provides the structural basis of
      the inhibitory mechanism of the enzyme that could be used to improve the potency
      of inhibitors against an important component of fatty acid synthesis common to
      many infectious organisms.

PMID- 21843646
TI  - Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response
      with increasing age.
AB  - fMRI studies of aging have revealed increased blood oxygenation level dependent
      (BOLD) response to tasks of executive function with advancing age, which is
      generally interpreted as increased neural activity. However, changes in the
      cerebrovascular system with age can alter the BOLD signal, complicating this
      interpretation. Arterial spin labeling (ASL) allows simultaneous acquisition of
      BOLD and cerebral blood flow (CBF) information and can be used to quantify the
      component parts of the BOLD signal. We used this calibrated BOLD approach in 58
      healthy participants over an age range of 18-71 years to determine the relative
      vascular and neuronal contributions to the age-related BOLD changes in response
      to a Stroop task. The percentage BOLD response increased significantly with
      increasing age but the percentage CBF response did not alter, such that the BOLD
      increase is attributed to a significant reduction in the oxygen metabolism
      response with increasing age. Hence, in this study, the BOLD increase with age
      should be interpreted as a reduction in neural activity. The greatest percentage
      BOLD increases with age were found in the left and right medial frontal gyri and
      the primary motor cortex and were again linked to a reduction in oxygen
      metabolism. On separating the participants into three groups (young, old high
      performers and old low performers), age-related differences in percentage BOLD
      response and oxygen metabolism response could be attributed to the low performing
      old group. This study demonstrates the need to take into account alterations in
      vascular-metabolic coupling and resting blood volume when interpreting changes in
      the BOLD response with aging.

PMID- 21843647
TI  - Phylogenetic utility and evolution of indels: a study in neognathous birds.
AB  - Indels are increasingly used in phylogenetics and play a major role in genome
      size evolution, and yet both the phylogenetic information content of indels and
      their evolutionary significance remain to be better assessed. Using three
      presumably independently evolving nuclear gene fragments (28S rDNA, beta
      fibrinogen, ornithine decarboxylase) from 29 families of neognathous birds, we
      have obtained a topology that is in general agreement with the current molecular
      consensus tree, supports the monophyly of Metaves, and provides evidence for the
      unresolved relationships within the Charadriiformes. Based on the retrieved
      topology, we assess the relative impact of indels and nucleotide substitutions
      and demonstrate that the superposition of the two kinds of data yields a topology
      that could not be obtained from either data set alone. Although only two out of
      three gene fragments reveal the deletion bias, the combined nucleotide insertion
      to-deletion ratio is 0.22, indicating a rapid decrease of intron length. The
      average indel fixation rate in the neognaths is 2.5 times faster than that in
      therian (placental) mammals of similar geologic age. As in mammals, there is a
      considerable variation of indel fixation rate that is 1.5 times higher in
      Galloanseres compared to Neoaves, and 2.4 times higher in the Rallidae compared
      to the average for Neoaves (8.2 times higher compared to the related Gruidae).
      Our results add to the evidence that indel fixation rates correlate with lineage
      specific evolutionary rates.

PMID- 21843648
TI  - Antibody drug conjugates - Trojan horses in the war on cancer.
AB  - Antibody drug conjugates (ADCs) consist of an antibody attached to a cytotoxic
      drug by means of a linker. ADCs provide a way to couple the specificity of a
      monoclonal antibody (mAb) to the cytotoxicity of a small-molecule drug and,
      therefore, are promising new therapies for cancer. ADCs are prodrugs that are
      inactive in circulation but exert their cytotoxicity upon binding to the target
      cancer cell. Earlier unsuccessful attempts to generate ADCs with therapeutic
      value have emphasized the important role each component plays in determining the
      efficacy and safety of the final ADC. Scientific advances in engineering
      antibodies for maximum efficacy as anticancer agents, identification of highly
      cytotoxic molecules, and generation of linkers with increased stability in
      circulation have all contributed to the development of the many ADCs that are
      currently in clinical trials. This review discusses parameters that guide the
      selection of the components of an ADC to increase its therapeutic window,
      provides a brief look at ADCs currently in clinical trials, and discusses future
      challenges in this field.

PMID- 21843649
TI  - Comparative analysis with collagen type II distinguishes cartilage oligomeric
      matrix protein as a primary TGFbeta-responsive gene.
AB  - OBJECTIVE: This study aims to investigate the regulation of expression of
      Cartilage oligomeric matrix protein (COMP), which is predominately expressed by
      chondrocytes and functions to organize the extracellular matrix. Mutations in
      COMP cause two skeletal dysplasias: pseudoachondroplasia and multiple epiphyseal
      dysplasia. The mechanism controlling COMP expression during chondrocyte
      differentiation is still poorly understood. DESIGN: Primary human bone marrow
      derived stem cells were induced to differentiate into chondrocyte by pellet
      cultures. We then compared the temporal expression of COMP with the well
      characterized cartilage-specific Type II collagen (Col2a1), and their response to
      transforming growth factor (TGF)beta and Sox trio (Sox5, 6, and 9) stimulation.
      RESULTS: COMP and Col2a1 expression are differentially regulated by three
      distinct mechanisms. First, upregulation of COMP mRNA precedes Col2a1 by several
      days during chondrogenesis. Second, COMP expression is independent of high cell
      density but requires TGF-beta1. Induction of COMP mRNA by TGF-beta1 is detected
      within 2h in the absence of protein synthesis and is blocked by specific
      inhibitors of the TGFbeta signaling pathway; and therefore, COMP is a primary
      TFGbeta-response gene. Lastly, while Col2a1 expression is intimately controlled
      by the Sox trio, overexpression of Sox trio fails to activate the COMP promoter.
      CONCLUSION: COMP and Col2a1 expression are regulated differently during
      chondrogenesis. COMP is a primary response gene of TGFbeta and its fast induction
      during chondrogenesis suggests that COMP is suitable for rapidly accessing the
      chondrogenic potential of stem cells.

PMID- 21843650
TI  - Changes in mechanics and composition of human talar cartilage anlagen during
      fetal development.
AB  - OBJECTIVE: Fetal cartilage anlage provides a framework for endochondral
      ossification and organization into articular cartilage. We previously reported
      differences between mechanical properties of talar cartilage anlagen and adult
      articular cartilage. However, the underlying development-associated changes
      remain to be established. Delineation of the normal evolvement of mechanical
      properties and its associated compositional basis provides insight into the
      natural mechanisms of cartilage maturation. Our goal was to address this issue.
      MATERIALS AND METHODS: Human fetal cartilage anlagen were harvested from the tali
      of normal stillborn fetuses from 20 to 36 weeks of gestational age. Data obtained
      from stress relaxation experiments conducted under confined and unconfined
      compression configurations were processed to derive the compressive mechanical
      properties. The compressive mechanical properties were extracted from a linear
      fit to the equilibrium response in unconfined compression, and by using the
      nonlinear biphasic theory to fit to the experimental data from the confined
      compression experiment, both in stress-relaxation. The molecular composition was
      obtained using Fourier transform infrared (FTIR), and spatial maps of tissue
      contents per dry weight were created using FTIR imaging. Correlative and
      regression analyses were performed to identify relationships between the
      mechanical properties and age, compositional properties and age, and mechanical
      vs compositional parameters. RESULTS: All of the compositional quantities and the
      mechanical properties excluding the Poisson's ratio changed with maturation.
      Stiffness increased by a factor of ~2.5 and permeability decreased by 20% over
      the period studied. Collagen content and degree of collagen integrity increased
      with age by ~3-fold, while the proteoglycan content decreased by 18%. Significant
      relations were found between the mechanical and compositional properties.
      CONCLUSION: The mechanics of fetal talar cartilage is related to its composition,
      where the collagen and proteoglycan network play a prominent role. An
      understanding of the mechanisms of early cartilage maturation could provide a
      framework to guide tissue-engineering strategies.

PMID- 21843651
TI  - Implantation of bone marrow-derived buffy coat can supplement bone marrow
      stimulation for articular cartilage repair.
AB  - OBJECTIVE: Bone marrow stimulation (BMS) has been regarded as a first line
      procedure for repair of articular cartilage. However, repaired cartilage from BMS
      is known to be unlike that of hyaline cartilage and its inner endurance is not
      guaranteed. The reason presumably came from a shortage of cartilage-forming cells
      in blood clots derived by BMS. In order to increase repairable cellularity, the
      feasibility of autologous bone marrow-derived buffy coat transplantation in
      repair of large full-thickness cartilage defects was investigated in this study.
      METHODS: Rabbits were divided into four groups: the defect remained untreated as
      a negative control; performance of BMS only (BMS group); BMS followed by
      supplementation of autologous bone marrow buffy coat (Buffy coat group);
      transplantation of autologous osteochondral transplantation (AOTS) as a positive
      control. RESULTS: Repair of cartilage defects in the Buffy coat group in a rabbit
      model was more effective than BMS alone and similar to AOTS. Gross findings,
      histological analysis, histological scoring, immunohistochemistry, and chemical
      assay demonstrated that supplementation of autologous bone marrow buffy coat
      after BMS arthroplasty effectively repaired cartilage defects in a rabbit model,
      and was more effective than BMS arthroplasty alone. CONCLUSION: Supplementation
      of autologous bone marrow-derived buffy coat in cases of BMS could be a useful
      clinical protocol for cartilage repair.

PMID- 21843652
TI  - Functional roles of synapsin: lessons from invertebrates.
AB  - Data collected from the invertebrate models have allowed to establish several of
      the basic mechanisms of neuronal function and pioneered the studies on the
      molecular and cellular mechanisms involved in behavioral responses. In the 1970s,
      the first synaptic proteins--including synapsin--being identified, the first
      attempts to evaluate their synaptic function were done using available
      invertebrate preparations. Forty years later, it appears that deductions made
      from invertebrate synapsin were largely validated in vertebrates, probably
      reflecting the phylogenic conservation of some specific synapsin sub-domains. In
      this review, in light of insights got from invertebrate preparations, we discuss
      the role of synapsin in synaptogenesis and synaptic function, especially on short
      term plasticity.

PMID- 21843653
TI  - New insights in endosomal dynamics and AMPA receptor trafficking.
AB  - The trafficking mechanisms that control the density of synaptic AMPA-type
      glutamate receptors have received significant attention because of their
      importance for regulating excitatory synaptic transmission and synaptic
      plasticity in the hippocampus. AMPA receptors are synthesized in the neuronal
      cell body and reach their postsynaptic targets after a complex journey involving
      multiple transport steps along different cytoskeleton structures and through
      various stages of the endocytic pathway. Dendritic spines are important sites for
      AMPA receptor trafficking and contain the basic components of endosomal
      recycling. On induction of synaptic plasticity, internalized AMPA receptors
      undergo endosomal sorting and cycle through early endosomes and recycling
      endosomes back to the plasma membrane (model for long-term potentiation) or
      target for degradation to the lysosomes (model for long-term depression).
      Exciting new studies now provide insight in actin-mediated processes that
      controls endosomal tubule formation and receptor sorting. This review describes
      the path of AMPA receptor internalization up to sites of recycling and summarizes
      recent studies on actin-mediated endosomal receptor sorting.

PMID- 21843654
TI  - High prevalence of Opisthorchis viverrini infection in reservoir hosts in four
      districts of Khon Kaen Province, an opisthorchiasis endemic area of Thailand.
AB  - Khon Kaen, a northeastern province of Thailand, has been considered as one of the
      human opisthorchiasis endemic areas with continuing high prevalence. Unsuccessful
      eradication of the disease is probably from the culture of eating raw and
      undercooked fish of local residence and the parasitic persistency in animal
      reservoir hosts, such as cats and dogs. In cooperation with the other human
      opisthorchiasis control programs in an endemic area of 29 villages in Ban Haet,
      Ban Phai, Chonnabot and Muncha Khiri Districts, Khon Kaen, this study
      investigated the prevalence of Opisthorchis viverrini infection using a formalin
      ether sedimentation method as the gold standard, and hematology and blood
      chemistry of the reservoir hosts in this endemic area. The results showed that
      cats had much higher prevalence (76 of 214, 35.51%) than dogs (3 of 821, 0.37%).
      Hematology between the infected and uninfected cats was not different. Complete
      blood count and biochemistry reflected some altered hepatic functions. However,
      only severely infected cats showed apparent clinical signs, including lethargy,
      diarrhea, ocular and nasal discharges. Moreover, the ultrasonogram of infected
      cats with very high egg per gram (>1500 EPG) showed apparent thickening of the
      gall bladder wall with hyperechoicity of hepatic parenchyma. This study suggests
      that cat is the most important animal reservoir of human opisthorchiasis,
      especially in this endemic area. It is also interesting that villages with
      infection are mostly located in the vicinity of Chi River and two large water
      reservoirs (Lawa and Nong Kongkaew Lakes), but people without infection were away
      from Chi River, on the south of Kudkhow Lake. Further investigation on this
      particular geofactor is essential for effective opisthorchiasis control programs.

PMID- 21843655
TI  - Eight genes expression patterns during visual system regeneration in Dugesia
      japonica.
AB  - Dugesia japonica has become the suitable model system for studying the visual
      system molecular developmental processes because of their simple structure and
      high regenerative capacity. To further dissect the molecular events of genetic
      network controlling the visual system regeneration in D. japonica, we
      investigated the morphogenesis of regenerating eyes under the stereomicroscope
      and the transcripts expression levels of eight genes involved in this process by
      quantitative real-time PCR. The eight genes were Djeya, Djsix-1, Eye53, DjotxA,
      Djpax6, Djopsin, Djnetrin and 1020HH. The results showed that each gene was of
      different expression pattern at distinct regeneration stage and these eight genes
      could be divided into three groups according to the expression levels at
      different time points and the morphogenesis during eye reconstruction: (1) the
      early expression group, including Djeya, Djsix-1, Eye53, and DjotxA, which
      expression levels were significant increase from 1 to 3days after amputation; (2)
      the medium-term expression group, only including one gene, Djpax6, which
      expression level reached the peak on day 5; and (3) the late expression genes,
      including Djopsin, Djnetrin and 1020HH, which gradually increase transcription
      with the eye regeneration. Our data suggested that eye reconstruction was the
      results of polygenic services and the genes in the same group might have similar
      role or function in symphony.

PMID- 21843656
TI  - Gadd45a, Gadd45b and Gadd45g expression during mouse embryonic development.
AB  - Gadd45 proteins have been implicated in the cellular response to physiological or
      environmental stress and the accompanying cell cycle arrest, DNA repair, cell
      survival and senescence or apoptosis. Although their molecular function is well
      studied, the expression and role of Gadd45 genes during embryonic development in
      mice is largely unknown. Here we provide a comprehensive comparison of Gadd45a,
      Gadd45b and Gadd45g expression during mouse embryonic development. In situ
      hybridizations on sectioned and whole mouse embryos show most prominent Gadd45a
      expression in the tip of the closing neural tube, the cranial and dorsal root
      ganglia and the somites. Mouse Gadd45b is expressed strongly in the chorion, but
      only weakly in the embryo proper, including somites and limb buds. Murine Gadd45g
      expression strongly resembles Xenopus and medaka fish expression in primary
      neuron precursors and post-mitotic neurons, indicating a conserved role for
      Gadd45g in vertebrate neurogenesis. Additionally, Gadd45 genes show conserved
      expression during somitogenesis. In summary, Gadd45 genes are expressed in
      evolutionary conserved, but also divergent domains, which predominantly encompass
      areas of cell differentiation, consistent with their established function in
      growth arrest and DNA demethylation.

PMID- 21843657
TI  - Origin and evolution of the worldwide distributed pathogenic amoeboflagellate
      Naegleria fowleri.
AB  - Naegleria fowleri, a worldwide distributed pathogen, is the causative agent of
      primary amoebic meningoencephalitis. Because it is such a fulminant disease, most
      patients do not survive the infection. This pathogen is a free-living
      amoeboflagellate present in warm water. To date, it is well established that
      there are several types of N. fowleri, which can be distinguished based on the
      length of the internal transcribed spacer 1 and a one bp transition in the 5.8S
      rDNA. Seven of the eight known types have been detected in Europe. Three types
      are present in the USA, of which one is unique to this country. Only one of the
      eight types occurs in Oceania (Australia and New Zealand) and Japan. In mainland
      Asia (India, China and Thailand) the two most common types are found, which are
      also present in Europe and the USA. There is strong indication that the
      pathogenic N. fowleri evolved from the nonpathogenic Naegleria lovaniensis on the
      American continent. There is no evidence of virulence differences between the
      types of N. fowleri. Two other Naegleria spp. are pathogenic for mice, but human
      infections due to these two other Naegleria spp. are not known.

PMID- 21843659
TI  - Astrovirus infections in humans and animals - molecular biology, genetic
      diversity, and interspecies transmissions.
AB  - Astroviruses are small, non-enveloped, positive sense, single-stranded RNA
      viruses first identified in 1975 in children suffering from diarrhea and then
      described in a wide variety of animals. To date, the list of animal species
      susceptible to astrovirus infection has expanded to 22 animal species or
      families, including domestic, synantropic and wild animals, avian, and mammalian
      species in the terrestrial and aquatic environments. Astrovirus infections are
      considered among the most common cause of gastroenteritis in children, second
      only to rotavirus infections, but in animals their association with enteric
      diseases is not well documented, with the exception of turkey and mink astrovirus
      infection. Genetic variability has been described in almost all astrovirus
      species sufficiently examined infecting mammals and birds; however, antigenic
      variability has been demonstrated for human astroviruses but is far less
      investigated in animal viruses. Interestingly, there is an increasing evidence of
      recombination events occurring in astroviruses, which contributes to increase the
      genetic variability of this group of viruses. A wide variety of species infected,
      the evident virus genetic diversity and the occurrence of recombination events
      indicate or imply either cross-species transmission and subsequent virus
      adaptation to new hosts or the co-infection of the same host with different
      astroviruses. This can also favor the emergence of novel astroviruses infecting
      animals or with a zoonotic potential. After more than 30 years from their first
      description in humans, there are many exciting streams of research to be explored
      and intriguing questions that remain to be answered about the relatively under
      studied Astroviridae family. In the present work, we will review the existing
      knowledge concerning astrovirus infections in humans and animals, with particular
      focus on the molecular biology, interspecies transmission and zoonotic potential
      of this group of viruses.

PMID- 21843660
TI  - Hematologic toxicities associated with intravenous immunoglobulin therapy.
AB  - Intravenous immunoglobulin (IVIG) is an immunomodulating agent that induces
      beneficial therapeutic responses in children and adults. IVIG is not only used
      for prophylaxis and therapy of infections in patients with primary and secondary
      immunodeficiencies associated with defective antibody production, but also used
      for treatment of patients with systemic inflammatory disorders, autoimmune
      diseases, and neuroimmunologic conditions. IVIG is generally considered a safe
      and efficacious therapeutic modality. However, it is associated with certain
      adverse effects including hematologic complications such as hemolytic anemia,
      leukopenia, neutropenia, monocytopenia, disseminated intravascular coagulation,
      and changes in blood rheology. Venous and arterial thrombotic complications can
      also occur following treatment with IVIG in high risk patients. It is very
      important for clinicians to have the knowledge of those adverse events profiles;
      and this article summarizes hematologic toxicities associated with IVIG therapy
      reported in the literature; and describes strategies for their identification and
      management.

PMID- 21843661
TI  - Microglia and cyclooxygenase-2: possible therapeutic targets of progesterone for
      stroke.
AB  - Previous studies have demonstrated that progesterone (PROG) may be a pleiotropic
      neuroprotective agent. Although there have been reports about the neurotoxicity
      of activated microglia and cyclooxygenase-2 (COX-2) in animal models of ischemic
      stroke, the influence of PROG on the activation of microglia and the expression
      of COX-2 after stroke has not been examined in detail. In this investigation, we
      carried out research about the influence of PROG on cultured microglia by
      detection of the expression of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) in their supernatant fluid before and after induced
      with lipopolysaccharide (LPS) or influenced by PROG with Enzyme-Linked
      Immunosorbent Assay technique in vitro. Moreover, the expression of COX-2 and
      ionized calcium-binding adapter molecule 1 (Iba1) was also detected in the cortex
      of rats that underwent permanent middle cerebral artery occlusion and received
      PROG or vehicle treatment by immunohistochemistry and western blot technique. The
      results revealed that PROG significantly reduced the expression of TNF-alpha and
      IL-1beta in cultured microglia after activated with LPS in vitro. In addition,
      PROG also valuably inhibited the expression of Iba1 and COX-2 after stroke in
      vivo. These observations raised the possibility that PROG can exert its
      neuroprotective effects by inhibiting the activation of microglia and the over
      expression of COX-2 after stroke.

PMID- 21843662
TI  - Stability studies of extracellular domain two of neural-cadherin.
AB  - Neural- (NCAD) and epithelial- (ECAD) cadherin are calcium-dependent cell
      adhesive molecules, and are localized at excitatory and inhibitory synapses
      respectively. They play an important role in synaptogenesis, synapse maintenance
      and plasticity. The extracellular region plays a critical role in cadherin
      mediated cell adhesion, and has five tandemly repeated ectodomains (EC1-EC5).
      Calcium binding is required for dimer formation between first two N-terminal
      domains (EC1-EC2). Despite similarity in the primary structure, the extracellular
      domains of NCAD and ECAD have different intrinsic stability, dimerization
      affinity and kinetics of disassembly. To investigate the origin of these
      differences, we are characterizing the modular domains individually. Here, we
      report studies of NCAD2, EC2 of NCAD. This domain is important for calcium
      binding and is the physical linkage between the dimerization interface in EC1 and
      the membrane proximal modular domains. Thermal-denaturation studies show that
      NCAD2 is less stable than ECAD2 and less influenced by the adjoining 7-residue, N
      and C-terminal linker segments. In addition the NCAD2 constructs are less
      influenced by added salt. This difference is likely due to variation in the
      overall number and distribution of charges on these anionic proteins. Our studies
      indicate that despite their sequence similarity and apparently passive role in
      adhesive dimer formation, EC2 of E- and N-cadherins are distinctly different and
      may contribute to the differences in energetics and kinetics of dimerization.

PMID- 21843663
TI  - Microstructure and mechanical properties of as-cast Zr-Nb alloys.
AB  - On the basis of the microstructures and mechanical properties of as-cast Zr-(0
      24)Nb alloys the effects of phase constitution on the mechanical properties and
      magnetic susceptibility are discussed in order to develop Zr alloys for use in
      magnetic resonance imaging (MRI). The microstructures were evaluated using an X
      ray diffractometer, an optical microscope, and a transmission electron
      microscope; the mechanical properties were evaluated by a tensile test. The
      alpha' phase was dominantly formed with less than 6 mass% Nb content. The omega
      phase was formed in Zr-(6-20)Nb alloys, but disappeared from Zr-22Nb. The beta
      phase dominantly existed in Zr-(9-24)Nb alloys. The mechanical properties as well
      as the magnetic susceptibility of the Zr-Nb alloys varied depending on the phase
      constitution. The Zr-Nb alloys consisting of mainly alpha' phase showed high
      strength, moderate ductility, and a high Young's modulus, retaining low magnetic
      susceptibility. Zr-Nb alloys containing a larger volume of omega phase were found
      to be brittle and, thus, should be avoided, despite their low magnetic
      susceptibility. When the Zr-Nb alloys consisted primarily of beta phase the
      effect of omega phase weakened the mechanical properties, thereby leading to an
      increase in ductility, even with an increase in magnetic susceptibility. The
      minimum value of Young's modulus was obtained for Zr-20Nb, because this
      composition was the phase boundary between the beta and omega phases. However,
      the magnetic susceptibility of the alloy was half that of Ti-6Al-4V alloys. Zr-Nb
      alloys consisting of alpha' or beta phase have excellent mechanical properties
      with low magnetic susceptibility and, thus, these alloys could be useful for
      medical devices used in MRI.

PMID- 21843658
TI  - Population genetics, taxonomy, phylogeny and evolution of Borrelia burgdorferi
      sensu lato.
AB  - In order to understand the population structure and dynamics of bacterial
      microorganisms, typing systems that accurately reflect the phylogenetic and
      evolutionary relationship of the agents are required. Over the past 15 years
      multilocus sequence typing schemes have replaced single locus approaches, giving
      novel insights into phylogenetic and evolutionary relationships of many bacterial
      species and facilitating taxonomy. Since 2004, several schemes using multiple
      loci have been developed to better understand the taxonomy, phylogeny and
      evolution of Lyme borreliosis spirochetes and in this paper we have reviewed and
      summarized the progress that has been made for this important group of vector
      borne zoonotic bacteria.

PMID- 21843664
TI  - Inhibition of smooth muscle cell adhesion and proliferation on heparin-doped
      polypyrrole.
AB  - We have investigated the application of polypyrrole (pPy) as a material to
      influence neointimal cell behaviour. The physico-chemical properties of pPy doped
      with heparin (Hep), para-toluene sulfonate, poly(2-methoxyaniline-5-sulfonic
      acid) (pMAS) and nitrate ions were studied in addition to cell adhesion and
      proliferation studies of neointimal relevant cell lines cultured on the pPy
      substrates. Both smooth muscle (hSMC) and endothelial (hEC) cell types adhered
      and proliferated best on the smooth, hydrophilic pPy/pMAS material. Moreover,
      pPy/Hep is able to support the proliferation of hECs on the surface but inhibits
      hSMC proliferation after 4 days of culture. The inhibitory effect on hSMCs is
      most likely due to the well-known antiproliferative effect of heparin on hSMC
      growth. The results presented indicate that surface exposed heparin binds to the
      putative heparin receptor of hSMCs and is sufficient to inhibit proliferation.
      The application of galvanostatically synthesized pPy/Hep to stent surfaces
      presents a novel bioactive control mechanism to control neointimal cell growth.

PMID- 21843665
TI  - A bootstrap-based regression method for comprehensive discovery of differential
      gene expressions: an application to the osteoporosis study.
AB  - A common purpose of microarray experiments is to study the variation in gene
      expression across the categories of an experimental factor such as tissue types
      and drug treatments. However, it is not uncommon that the studied experimental
      factor is a quantitative variable rather than categorical variable. Loss of
      information would occur by comparing gene-expression levels between groups that
      are factitiously defined according to the quantitative threshold values of an
      experimental factor. Additionally, lack of control for some sensitive clinical
      factors may bring serious false positive or negative findings. In the present
      study, we described a bootstrap-based regression method for analyzing gene
      expression data from the non-categorical microarray experiments. To illustrate
      the utility of this method, we applied it to our recent gene-expression study of
      circulating monocytes in subjects with a wide range of variations in bone mineral
      density (BMD). This method allows a comprehensive discovery of gene expressions
      associated with osteoporosis-related traits while controlling other common
      confounding factors such as height, weight and age. Several genes identified in
      our study are involved in osteoblast and osteoclast functions and bone remodeling
      and/or menopause-associated estrogen-dependent pathways, which provide important
      clues to understand the etiology of osteoporosis. AVAILABILITY: SAS code is
      available from the authors upon request.

PMID- 21843666
TI  - A proteomics view of programmed cell death mechanisms during host-parasite
      interactions.
AB  - Protozoan parasites are responsible for an impressive disease burden in
      developing and less-developed countries. The development of vaccines and
      effective new therapies for dealing with these organisms are among the main gaps
      to be filled in the control of protozoan parasite diseases. Programmed cell death
      (PCD) pathways have gained attention in recent years because they comprise
      complex signalling pathways that can be explored for therapeutic developments. In
      addition, high-resolution proteomics approaches offer the opportunity to
      determine protein patterns associated with either cell survival or cell death.
      This review will focus on proteomics studies of PCD mechanisms during host
      protozoan parasite interactions.

PMID- 21843667
TI  - Proteomic analysis of advanced colorectal cancer by laser capture microdissection
      and two-dimensional difference gel electrophoresis.
AB  - The emergence of laser capture microdissection (LCM) and two-dimensional
      difference gel electrophoresis (2D-DIGE) has been shown to greatly improve the
      accuracy and sensitivity of global protein expression analysis. However, their
      combined use in profiling tumour proteome has rarely been reported. In this
      study, we applied these techniques to profile the protein expression changes of
      the late stage colorectal cancer (CRC) and its liver metastases. The study
      revealed that both the primary and secondary tumours showed a distinct protein
      expression profile compared to normal tissues, but were indistinguishable from
      each other. Differential analysis between the primary tumour and patient-matched
      normal colon mucosa identified a total of 71 proteins to be altered in CRC. Over
      40% of these proteins have been previously reported as CRC-related proteins,
      validating the accuracy of the current analysis. We have also identified many
      previously unknown changes including overexpression of ACY1, HSC70, HnRNP I,
      HnRNP A3, SET, ANP32A and TUFM in CRC, which have been further verified by
      western blotting and immunohistochemistry. This study demonstrated that LCM in
      combination with 2D-DIGE is a powerful tool to analyse the proteome of tumour
      tissues and may lead to the identification of potential novel protein markers and
      therapeutic targets for cancer.

PMID- 21843669
TI  - Simultaneous electrochemical determination of arsenic, copper, lead and mercury
      in unpolluted fresh waters using a vibrating gold microwire electrode.
AB  - In this work, a simple, rapid, reliable and low cost method for simultaneous
      electrochemical determination of As, Cu, Hg and Pb ions, on a vibrating gold
      microwire electrode combined with stripping voltammetry, is described for the
      first time. The multi-element detection was performed in the presence of oxygen
      by differential pulse anodic stripping voltammetry (DPASV) in HCl 0.1 M with NaCl
      0.5 M. This media was found optimum in terms of peak resolution, peak shape and
      sensitivities, and has a composition similar to seawater to which the method
      could potentially be applied. The gold microwire electrode presented well
      defined, undistorted, sharp and reproducible peaks for trace concentrations of
      Cu, Hg and Pb and As presented a reproducible peak with a small shoulder. Using a
      gold vibrating microwire electrode of 25 MUm diameter and 30s deposition time,
      the detection limits of As, Cu, Hg and Pb were 0.07, 0.4, 0.07 and 0.2 MUgL(-1),
      respectively. Possible effects of Al, Cd, Cr, Fe, Mn, Ni, Sb and Zn were
      investigated but did not cause any significant interferences. Finally, the method
      was applied for the simultaneous determination of these four metals in unpolluted
      river water samples and the results were validated by Atomic Absorption
      Spectroscopy with Electrothermal Atomization (AAS-EA) or by Inductively Coupled
      Plasma Mass Spectrometry (ICP-MS).

PMID- 21843668
TI  - Molecular call and response: the physiology of bacterial small RNAs.
AB  - The vital role of bacterial small RNAs (sRNAs) in cellular regulation is now well
      established. Although many diverse mechanisms by which sRNAs bring about changes
      in gene expression have been thoroughly described, comparatively less is known
      about their biological roles and effects on cell physiology. Nevertheless, for
      some sRNAs, insight has been gained into the intricate regulatory interplay that
      is required to sense external environmental and internal metabolic cues and turn
      them into physiological outcomes. Here, we review examples of regulation by
      selected sRNAs, emphasizing signals and regulators required for sRNA expression,
      sRNA regulatory targets, and the resulting consequences for the cell. We
      highlight sRNAs involved in regulation of the processes of iron homeostasis
      (RyhB, PrrF, and FsrA) and carbon metabolism (Spot 42, CyaR, and SgrS).

PMID- 21843670
TI  - Pressurized liquid extraction as a green approach in food and herbal plants
      extraction: A review.
AB  - Pressurized liquid extraction is a "green" technology for the extraction of
      nutraceuticals from foods and herbal plants. This review discusses the extraction
      principles and the optimization of the extraction parameters that improves the
      extraction efficiency. The use of different solvent mixtures and other extraction
      additives to enhance the efficiency of the extraction are discussed. Dynamic mode
      of extraction in Pressurized liquid extraction, and the use of combined and
      hyphenated sample preparation and analytical techniques are presented. This work
      discusses how different studies used Pressurized liquid extraction to enrich
      phenolic compounds, lignans, carotenoids, oils and lipids, essential oils and
      other nutraceuticals from foods and herbal plants.

PMID- 21843671
TI  - Tools for analyzing the phosphoproteome and other phosphorylated biomolecules: a
      review.
AB  - Enrichment, separation and mass spectrometric analysis of biomolecules carrying a
      phosphate group plays an important role in current analytical chemistry.
      Application areas range from the preparative enrichment of phospholipids for
      biotechnological purposes and the separation and purification of plasmid DNA or
      mRNA to the specific preconcentration of phosphoproteins and -peptides to
      facilitate their later identification and characterization by mass spectrometry.
      Most of the recent improvements in this field were triggered by the need for
      phosphopeptide enrichment technology for the analysis of cellular protein
      phosphorylation events with the help of liquid chromatography-mass spectrometry.
      The high sensitivity of mass spectrometry and the possibility to combine this
      technique with different separation modes in liquid chromatography have made it
      the method of choice for proteome analysis. However, in the case of
      phosphoprotein analysis, the low abundance of the resulting phosphopeptides and
      their low quality fragment spectra interfere with the identification of
      phosphorylation events. Recent developments in phosphopeptide enrichment and
      fragmentation technologies successfully helped to overcome these limitations. In
      this review, we will focus on sample preparation techniques in the field of
      phosphoproteomics, but also highlight recent advancements for the analysis of
      other phosphorylated biomolecules.

PMID- 21843672
TI  - Potentiometric stripping analysis of antimony based on carbon paste electrode
      modified with hexathia crown ether and rice husk.
AB  - An electrochemical method based on potentiometric stripping analysis (PSA)
      employing a hexathia 18C6 (HT18C6) and rice husk (RH) modified carbon paste
      electrode (HT18C6-RH-CPE) has been proposed for the subnanomolar determination of
      antimony. The characterization of the electrode surface has been carried out by
      means of scanning electron microscopy, cyclic voltammetry, electrochemical
      impedance spectroscopy and chronocoulometry. By employing HT18C6-RH-CPE, a 12
      fold enhancement in the PSA signal (dt/dE) was observed as compared to plain
      carbon paste electrode (PCPE). Under the optimized conditions, dt/dE (sV(-1)) was
      proportional to the Sb(III) concentration in the range of 1.42*10(-8) to 6.89*10(
      11)M (r=0.9944) with the detection limit (S/N=3) of 2.11*10(-11)M. The practical
      analytical utilities of the modified electrode were demonstrated by the
      determination of antimony in pharmaceutical formulations, human hair, sea water,
      urine and blood serum samples. The prepared modified electrode showed several
      advantages, such as simple preparation method, high sensitivity, very low
      detection limit and excellent reproducibility. Moreover, the results obtained for
      antimony analysis in commercial and real samples using HT18C6-RH-CPE and those
      obtained by inductively coupled plasma-atomic emission spectrometry (ICP-AES) are
      in agreement at the 95% confidence level.

PMID- 21843674
TI  - Convenient, inexpensive quantification of elemental sulfur by simultaneous in
      situ reduction and colorimetric detection.
AB  - Rapid, inexpensive, and convenient methods for quantifying elemental sulfur
      (S(0)) with low or sub-MUgg(-1) limits of detection would be useful for a range
      of applications where S(0) can act as a precursor for noxious off-aromas, e.g.,
      S(0) in pesticide residues on winegrapes or as a contaminant in drywall. However,
      existing quantification methods rely on toxic reagents, expensive and cumbersome
      equipment, or demonstrate poor selectivity. We have developed and optimized an
      inexpensive, rapid method (~15 min per sample) for quantifying S(0) in complex
      matrices. Following dispersion of the sample in PEG-400 and buffering, S(0) is
      quantitatively reduced to H(2)S in situ by dithiothreitol and simultaneously
      quantified by commercially available colorimetric H(2)S detection tubes. By
      employing multiple tubes, the method demonstrated linearity from 0.03 to 100 MUg
      S(0) g(-1) for a 5 g sample (R(2)=0.994, mean CV=6.4%), and the methodological
      detection limit was 0.01 MUg S(0) g(-1). Interferences from sulfite or sulfate
      were not observed. Mean recovery of an S(0) containing sulfur fungicide in grape
      macerate was 84.7% with a mean CV of 10.4%. Mean recovery of S(0) in a colloidal
      sulfur preparation from a drywall matrix was 106.6% with a mean CV of 6.9%.
      Comparable methodological detection limits, sensitivity, and recoveries were
      achieved in grape juice, grape macerate and with 1g drywall samples, indicating
      that the methodology should be robust across a range of complex matrices.

PMID- 21843673
TI  - Selective determination of estrogenic compounds in water by microextraction by
      packed sorbents and a molecularly imprinted polymer coupled with large volume
      injection-in-port-derivatization gas chromatography-mass spectrometry.
AB  - A fully automated protocol consisting of microextraction by packed sorbents
      (MEPS) coupled with large volume injection-in-port-derivatization-gas
      chromatography-mass spectrometry (LVI-derivatization-GC-MS) was developed to
      determine endocrine disrupting compounds (EDCs) such as alkylphenols, bisphenol
      A, and natural and synthetic hormons in river and waste water samples. During
      method optimization, the extraction parameters as ion strength of the water
      sample, the MEPS extraction regime, the volume of organic solvent used for the
      elution/injection step, the type of elution solvents and the selectivity of the
      sorbents were studied. For optimum in-port-derivatization, 10 MUL of the
      derivatization reagent N,O-bis(trimethylsilyl)triufloroacetamide with 1% of
      trimethylchlorosilane (BSTFA+1% TMCS) was used. 17beta-Estradiol-molecularly
      imprinted polymer (MIP) and silica gel (modified with C-18) sorbents were
      examined for the enrichment of the target analytes from water samples and the
      obtained results revealed the high selectivity of the MIP material for extraction
      of substances with estrogen-like structures. Recovery values for most of the
      analytes ranged from 75 to 109% for the C18 sorbent and from 81 to 103% for the
      MIP material except for equilin (on C18 with only 57-66% recovery). Precision
      (n=4) of the entire analysis protocol ranged between 4% and 22% with both
      sorbents. Limits of detection (LODs) were at the low ngL(-1) level (0.02-87, C18
      and 1.3-22, MIP) for the target analytes.

PMID- 21843675
TI  - High-throughput and cost-effective global DNA methylation assay by liquid
      chromatography-mass spectrometry.
AB  - An affordable and fast liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method was developed for the accurate and precise determination of global DNA
      methylation levels in peripheral blood. Global DNA methylation extent was
      expressed as the ratio of methylated 2'-deoxycytidine (5MedC) to 2'
      deoxyguanosine (dG), which were obtained after DNA extraction and hydrolysis and
      determined by positive electrospray LC-ESI-MS/MS. The cost-effective internal
      standards (15)N(3)-dC and (15)N(5)-dG were incorporated for the accurate
      quantification of 5MedC and dG, respectively. The desired nucleoside analytes
      were separated and eluted by LC within 2.5 min on a reverse phase column with a
      limit of detection of 1.4femtomole on column for 5MedC. Sample preparation in 96
      well format has significantly increased the assay throughput and filtration was
      found to be a necessary step to assure precision. Precision was performed with
      repeated analysis of four DNA QC sample over 12 days, with mean intra- and inter
      day CVs of 6% and 11%, respectively. Accuracy was evaluated by comparison with a
      previously reported method showing a mean CV of 4% for 5 subjects analyzed.
      Furthermore, application of the assay using a benchtop orbitrap LCMS in exact
      mass full scan mode showed comparable sensitivity to tandem LCMS using multiple
      reaction monitoring.

PMID- 21843676
TI  - A competitive immunoassay with a surrogate calibrator curve for aflatoxin M1 in
      milk.
AB  - A green enzyme-linked immunosorbent assay (ELISA) to measure aflatoxin M(1)
      (AFM(1)) in milk was developed and validated with a surrogate calibrator curve.
      Polyclonal anti-idiotype (anti-Id) antibody, used as an AFM(1) surrogate, was
      generated by immunizing rabbits with F(ab')(2) fragments from the anti-AFM(1)
      monoclonal antibody (mAb). The rabbits exhibited high specificity to the anti
      AFM(1) mAb, and no cross-reactivity to either of the other anti-aflatoxin mAbs or
      the isotype matched mAb was observed. After optimizing the physicochemical
      factors (pH and ionic strength) that influence assay performance, a quantitative
      conversion formula was developed between AFM(1) and the anti-Id antibody
      (y=31.91x-8.47, r=0.9997). The assay was applied to analyze AFM(1) in spiked milk
      samples. The IC(50) value of the surrogate calibrator curve was 2.4 MUg mL(-1),
      and the inter-assay and intra-assay variations were less than 10.8%; recovery
      ranged from 85.2 to 110.9%. A reference high-performance liquid chromatography
      method was used to validate the developed method, and a good correlation was
      obtained (y=0.81x+9.82, r=0.9922).

PMID- 21843677
TI  - The impact of water and hydrocarbon concentration on the sensitivity of a polymer
      based quartz crystal microbalance sensor for organic compounds.
AB  - Long-term environmental monitoring of organic compounds in natural waters
      requires sensors that respond reproducibly and linearly over a wide concentration
      range, and do not degrade with time. Although polymer coated piezoelectric based
      sensors have been widely used to detect hydrocarbons in aqueous solution, very
      little information exists regarding their stability and suitability over extended
      periods in water. In this investigation, the influence of water aging on the
      response of various polymer membranes [polybutadiene (PB), polyisobutylene (PIB),
      polystyrene (PS), polystyrene-co-butadiene (PSB)] was studied using the quartz
      crystal microbalance (QCM). QCM measurements revealed a modest increase in
      sensitivity towards toluene for PB and PIB membranes at concentrations above 90
      ppm after aging in water for 4 days. In contrast, the sensitivity of PS and PSB
      coated QCM sensors depended significantly on the toluene concentration and
      increased considerably at concentrations above 90 ppm after aging in water for 4
      days. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR
      FTIR) showed that there is a change in the sorption mechanism at higher toluene
      levels for PS and PSB. Positron annihilation lifetime spectroscopy (PALS) studies
      were performed to investigate the free volume properties of all polymers and to
      monitor any changes in the free volume size and distribution due to water and
      toluene exposure. The PALS did not detect any considerable variation in the free
      volume properties of the polymer films as a function of solution composition and
      soaking time, implying that viscoelastic and/or interfacial processes (i.e.
      surface area changes) are probably responsible for variations in the QCM
      sensitivity at high hydrocarbon concentrations. The results suggest that polymer
      membrane conditioning in water is an issue that needs to be considered when
      performing QCM measurements in the aqueous phase. In addition, the study shows
      that the hydrocarbon response is concentration dependant for polymers with a high
      glass transition temperature, and this feature is often neglected when comparing
      sensor sensitivity in the literature.

PMID- 21843678
TI  - Surface plasmon resonance biosensor with high anti-fouling ability for the
      detection of cardiac marker troponin T.
AB  - Designing a surface recognition layer with high anti-fouling ability, high
      affinity, and high specificity is an important issue to produce high sensitivity
      biosensing transducers. In this study, a self-assembled monolayer (SAM)
      consisting of a homogeneous mixture of oligo(ethylene glycol) (OEG)-terminated
      alkanethiolate and mercaptohexadecanoic acid (MHDA) on Au was employed for
      immobilizing troponin T antibody and applied in detecting cardiac troponin T by
      using surface plasmon resonance (SPR). The mixed SAM showed no phase segregation
      and exhibited human serum albumin resistance, particularly with an antibody
      immobilized surface. X-ray photoemission spectra revealed that the chemical
      composition ratio of OEG to the mixed SAM was 69% and the OEG packing density was
      82%. The specific binding of troponin T on the designed surface indicated a good
      linear correlation (R=0.991, P<0.0009) at concentrations lower than 50 MUgmL(-1)
      with the limit of detection of 100 ngmL(-1) using a SPR measuring instrument. It
      is concluded that the mixed SAM functions as designed since it has high detection
      capability, high accuracy and reproducibility, as well as shows strong potential
      to be applied in rapid clinical diagnosis for label-free detection within 2 min.

PMID- 21843679
TI  - Oxidase-functionalized Fe(3)O(4) nanoparticles for fluorescence sensing of
      specific substrate.
AB  - This study reports the development of a reusable, single-step system for the
      detection of specific substrates using oxidase-functionalized Fe(3)O(4)
      nanoparticles (NPs) as a bienzyme system and using amplex ultrared (AU) as a
      fluorogenic substrate. In the presence of H(2)O(2), the reaction pH between
      Fe(3)O(4) NPs and AU was similar to the reaction of oxidase and the substrate.
      The catalytic activity of Fe(3)O(4) NPs with AU was nearly unchanged following
      modification with poly(diallyldimethylammonium chloride) (PDDA). Based on these
      features, we prepared a composite of PDDA-modified Fe(3)O(4) NPs and oxidase for
      the quantification of specific substrates through the H(2)O(2)-mediated oxidation
      of AU. By monitoring fluorescence intensity at 587 nm of oxidized AU, the minimum
      detectable concentrations of glucose, galactose, and choline were found to be 3,
      2, and 20 MUM using glucose oxidase-Fe(3)O(4), galactose oxidase-Fe(3)O(4), and
      choline oxidase-Fe(3)O(4) composites, respectively. The identification of glucose
      in blood was selected as the model to validate the applicability of this proposed
      method.

PMID- 21843680
TI  - Enzyme-based NAND gate for rapid electrochemical screening of traumatic brain
      injury in serum.
AB  - We report on the development of a rapid enzyme logic gate-based electrochemical
      assay for the assessment of traumatic brain injury (TBI). The concept harnesses a
      biocatalytic cascade that emulates the functionality of a Boolean NAND gate in
      order to process relevant physiological parameters in the biochemical domain. The
      enzymatic backbone ensures that a high-fidelity diagnosis of traumatic brain
      injury can be tendered in a rapid fashion when the concentrations of key serum
      based biomarkers reach pathological levels. The excitatory neurotransmitter
      glutamate and the enzyme lactate dehydrogenase were used here as clinically
      relevant input TBI biomarkers, in connection to the low-potential detection of
      the NADH product in the presence of methylene green at a glassy carbon electrode.
      A systematic optimization of the gate and the entire protocol has resulted in the
      effective discrimination between the physiological and pathological logic levels.
      Owing to its robust design, the enzyme-based logic gate mitigates potential
      interferences from both physiological and electroactive sources and is able to
      perform direct measurements in human serum samples. Granted further detailed
      clinical validation, this proof-of-concept study demonstrates the potential of
      the electrochemical assay to aid in the rapid and decentralized diagnosis of TBI.

PMID- 21843681
TI  - Title X: a proud past, an uncertain future.

PMID- 21843682
TI  - Removing the black box warning for depot medroxyprogesterone acetate.

PMID- 21843683
TI  - Termination of second-trimester pregnancy by mifepristone combined with
      misoprostol versus intra-amniotic injection of ethacridine lactate (Rivanol(r)):
      a systematic review of Chinese trials.
AB  - BACKGROUND: Mifepristone combined with misoprostol for second-trimester abortion
      (MM) and intra-amniotic injection of ethacridine lactate (EL; Rivanol(r)) are the
      common methods for termination of second-trimester pregnancy in China. The
      systematic review of relevant literature was conducted to evaluate the
      effectiveness and safety on termination of second-trimester pregnancy using MM,
      introduced in 1988 in China, versus the Chinese routinely used method since 1970 
      - EL. The review was conducted to evaluate mifepristone combined with the
      misoprostol versus intra-amniotic injection of ethacridine lactate in China for
      termination of second-trimester pregnancy with respect to efficacy, side effects,
      complications and so on. STUDY DESIGN: The Cochrane Central Register of
      Controlled Trials, EMBASE, MEDLINE, POPLINE, TOXLINE, World Health Organization
      Department of Reproductive Health and Research, Chinese Biomedical Literature
      Database, Chinese Journal Full-text Database and Chinese Science & Technology
      Journal Database were systematically searched. Reference lists for English and
      Chinese-language reports (published from 1966 to 2008) were searched. All
      randomized controlled trials (RCTs) on second-trimester abortion by combination
      of mifepristone and misoprostol versus ethacridine lactate, which conducted in
      China, were analyzed. Trial quality was assessed, and data extraction was made
      independently by two reviewers. RESULTS: Fifteen original RCTs using MM versus EL
      were included. Three trials used oral misoprostol, six trials used vaginal
      misoprostol, and six trials used oral plus vaginal misoprostol. Failure rate of
      abortion was 2.0% to 5.9% in the MM group and 7.4% to 20.7% in the EL group. The
      incidence of postabortion curettage was similar in the two groups. The time of
      labor and hospitalization for abortion in the MM group were shorter compared with
      EL group. The blood loss within 2 h of abortion in the MM group was significantly
      less than that in the EL group, but the blood loss within 24 h of abortion was
      the same in both groups. More gastrointestinal side effects occurred with the MM
      regimen, whereas cervical injury occurred more often in the EL group.
      CONCLUSIONS: Compared with the intra-amniotic injection of ethacridine lactate,
      mifepristone/misoprostol has a higher success rate and shorter time of labor with
      more gastrointestinal side effects for termination of second-trimester pregnancy.

PMID- 21843684
TI  - Medical vs. surgical abortion: the importance of women's choice.
AB  - BACKGROUND: Using a large national sample of women undergoing an abortion in
      France, we explore the factors associated with medical or surgical abortion. We
      draw particular attention to the influence of women's preferences in the decision
      making process. STUDY DESIGN: The data are drawn from a nationally representative
      survey of 8,245 women undergoing an elective abortion in France in 2007. Analyses
      of factors associated with the type of abortion technique were performed among
      the 4,650 women who were identified as being eligible for the two techniques.
      RESULTS: Sixty-eight percent of all abortions were medical procedures among women
      eligible for both techniques. The type of abortion technique was not dependent on
      women's age, parity, cohabitation status, socioeconomic circumstances nor on the
      type of facility providing the abortion (private or public). Conversely, women's
      participation in the decision-making process was strongly associated with the
      type of abortion method. Among the 50% of women who reported they had been given
      a choice, 84% underwent a medical procedure vs. 52% of those who were not offered
      a choice. Among the 2,286 women who were not involved in the decision, 35%
      indicated they trusted their doctor to make the best choice for them, while 44%
      were told it was too late for a medical procedure, although they had consulted
      before 8 weeks of amenorrhea. CONCLUSION: In this sample of French women who
      participated in a national survey on abortion, those who were involved in the
      decision-making process as to whether to have a medical or surgical procedure
      showed a strong preference for the medical procedure.

PMID- 21843685
TI  - Ovulation resumption after medical abortion with mifepristone and misoprostol.
AB  - BACKGROUND: As an antiprogestin, mifepristone may have an impact on the return to
      ovulation in a manner that is not only attributable to its abortifacient
      activity. Our aim was to measure the time-to-ovulation in women who received
      mifepristone 200 mg orally and misoprostol 800 mcg vaginally for abortion up to
      63 days of gestation. STUDY DESIGN: This planned substudy was part of a
      multicenter randomized trial of mifepristone 200 mg followed immediately or 24 h
      later by misoprostol 800 mcg vaginally. Women who had successful expulsion of the
      gestational sac based on ultrasound examination 1 week after mifepristone
      treatment were enrolled. All subjects used nonhormonal contraception until study
      completion. Baseline serum progesterone (P) levels were drawn on day 8+/-1 after
      mifepristone administration and then twice weekly until the P level was >3 ng/mL,
      consistent with ovulation. The mean time-to-ovulation was calculated using
      interval censored regression to address the censoring due to participant
      discontinuation. RESULTS: Fourteen (52%) of 27 enrolled women completed the
      substudy. The longest period of time that a subject who did not complete the
      study was followed was 29 days. Ovulation occurred 20.6+/-5.1 (range 8-36) days
      after mifepristone administration. Time-to-ovulation was not affected by
      participant age, gestational age, study arm, body mass index or presence or
      absence of human chorionic gonadotropin. CONCLUSIONS: Return to ovulation
      following medical abortion with mifepristone and misoprostol occurs on average 3
      weeks postabortion. Mifepristone 200 mg does not appear to have a lasting effect
      on ovarian function. Our results should be contextualized by the small sample
      size, although this is one of the larger studies on return to ovulation after
      abortion.

PMID- 21843686
TI  - Effects of prophylactic misoprostol administration prior to intrauterine device
      insertion in nulliparous women.
AB  - BACKGROUND: This study was conducted to examine the effects of prophylactic
      misoprostol prior to intrauterine device (IUD) placement in nulliparous women.
      STUDY DESIGN: Nulliparous, reproductive-aged women desiring an IUD for
      contraception were randomized to receive 400 mcg of buccal misoprostol or placebo
      90 min prior to IUD insertion. Subjects completed a series of 100-mm visual
      analogue scales (VAS, anchors: 0=none, 100 mm=worst imaginable) to measure their
      perceived pain at several times points (anticipated pain, leg positioning,
      speculum placement, tenaculum placement, IUD insertion, equipment removal and 5
      min postinsertion). Secondary outcomes included provider "ease of placement" (100
      mm VAS, anchors: 0=easy, 100 mm=extremely difficult), side effects and retention
      of the IUD after 1 month (self-report or clinic visit). The study had 80% power
      (alpha=0.05, one-sided) to detect a reduction with treatment of 20 mm in VAS
      scores with a combined sample size of 34. RESULTS: A total of 40 subjects were
      randomized to receive either misoprostol or placebo, and 35 completed the study.
      Five subjects withdrew (four prior to receiving study medication and one declined
      IUD). Baseline characteristics were similar between groups. There were no
      significant differences in patient-reported pain with IUD placement [misoprostol
      65 mm (SD 21), placebo 55 mm (SD 21), p=.83] or at any other time point.
      Moreover, the misoprostol group reported significantly more preinsertion nausea
      (29% vs. 5%, p=.05) and cramping (47% vs. 16%, p=.04) than the placebo group.
      While provider-reported ease of insertion was not significantly different between
      groups, three placebo patients required additional dilation vs. none in the
      misoprostol group. All 35 subjects underwent follow-up at least 1 month
      postinsertion, and no expulsions were reported. CONCLUSION: Prophylactic
      misoprostol prior to IUD placement in nulliparous women did not reduce patient
      perceived pain, but it did appear to increase preinsertion side effects.

PMID- 21843687
TI  - Immediate postplacental insertion of an intrauterine contraceptive device during
      cesarean section.
AB  - BACKGROUND: An intrauterine device (IUD) is an effective reversible form of
      contraception. We determined the efficacy and safety of immediate postplacental
      IUD insertion during cesarean section. STUDY DESIGN: Two hundred forty-five women
      with term pregnancies delivering by cesarean section between September 2006 and
      December 2007 were included in the study. A copper IUD (TCu 380A) was inserted
      using a ring forceps within 10 min of removing the placenta. The participants
      were examined before hospital discharge and at 6 weeks, 6 months and 12 months
      postpartum. RESULTS: None of the patients were lost to follow-up. There was one
      case of an unplanned pregnancy (0.4%). There were no serious complications
      associated with immediate IUD insertion during cesarean section. The cumulative
      rates of expulsion, removal for bleeding/pain and other medical reasons were
      17.6, 8.2 and 2.4 per 100 women per year, respectively. The continuation rates
      were 81.6% and 62% at 6 and 12 months, respectively. CONCLUSION: Immediate
      postplacental IUD insertion during cesarean section provides adequate protection
      against pregnancy. However, greater than one fourth of the participants
      discontinued IUD use due to spontaneous expulsion or other medical reasons.

PMID- 21843688
TI  - Postpartum insertion of levonorgestrel--intrauterine system at three time
      periods: a prospective randomized pilot study.
AB  - BACKGROUND: The study was conducted to determine the feasibility of
      levonorgestrel-intrauterine system (LNG-IUS) insertion at three different times
      postpartum. STUDY DESIGN: From August 2009 to January 2010, all women desiring
      LNG-IUS for postpartum contraception were offered enrollment into our study and
      randomized to three insertion times: immediate (within 10 min of placenta
      delivery), early (10 min to 48 h postpartum) or interval (>=6 weeks postpartum).
      RESULTS: Forty-six women met inclusion criteria and were analyzed. There was no
      difference in utilization rates at 3 and 6 months between groups (p=.931).
      Expulsion rates were significantly higher and pain during insertion was
      significantly lower in the immediate and early groups (p<.001) when compared to
      the interval group. CONCLUSION: Insertion of LNG-IUS <=48 h postpartum is
      feasible in our institution and may be associated with similar utilization at 6
      months, increased expulsion rates and decreased pain at insertion when compared
      to placement after 6 weeks.

PMID- 21843689
TI  - Unintended pregnancy among women in the US military.
AB  - BACKGROUND: The study was conducted to examine the extent of unintended pregnancy
      among female active-duty military personnel in the US Armed Forces. STUDY DESIGN:
      Data consisted of representative data from active-duty women aged 18-44 years
      (n=3745) from the 2005 Department of Defense Survey of Health Related Behaviors
      Among Active Duty Military Personnel. The proportion of women with an unintended
      pregnancy in the last 12 months, the pregnancy rate and the percentage of all
      pregnancies in the last 12 months that were unintended were calculated. RESULTS:
      An estimated 54% of pregnancies were unintended, based on self-reports. After
      accounting for likely underreporting for abortion, the adjusted unintended
      pregnancy rate was 117 per 1000 women. Younger and less educated women had higher
      rates, as did enlisted women when compared to officers. CONCLUSION: Further
      efforts are needed to reduce unintended pregnancy among women in the military.

PMID- 21843690
TI  - Adherence to dual-method contraceptive use.
AB  - BACKGROUND: Patient characteristics associated with adherence to dual-method
      contraceptive use are not known. STUDY DESIGN: Project PROTECT was a 24-month
      long randomized trial designed to promote the use of dual methods of
      contraception using an individualized computer-based intervention or enhanced
      standard care counseling intervention. We analyzed 463 women with follow-up data
      and examined sustained dual-method use (reported at 2+ interviews). RESULTS:
      While 32% initiated dual-method contraceptive use, only 9% reported sustained
      use. Education increased (RR(adj)=4.42; 95% confidence interval [CI] 1.19-16.42),
      substance abuse decreased (adjusted relative risk [RR(adj)]=0.49; 95% CI 0.24
      0.97), no contraceptive use at baseline decreased (RR(adj)=0.32; 95% CI 0.11
      0.92) and contraceptive stage of change increased (RR(adj)=5.04; 95% CI 1.09
      23.4) adherence to dual-method use. CONCLUSION: To effectively prevent sexually
      transmitted diseases and unplanned pregnancies, dual-method use must be
      consistent and sustained. Future interventions to promote dual-method use should
      focus on high-risk groups and additional dual-method combinations (e.g., barrier
      plus intrauterine devices or implants).

PMID- 21843691
TI  - Adolescents, contraception and confidentiality: a national survey of obstetrician
      -gynecologists.
AB  - BACKGROUND: Given recent legislative efforts to require parental notification for
      the provision of reproductive health care to minors, we sought to assess how
      obstetrician-gynecologists (Ob/Gyns) respond to requests for confidential
      contraceptive services. STUDY DESIGN: Mailed survey of 1800 US Ob/Gyns, utilizing
      a vignette where a 17-year-old college freshman requests birth control pills and
      does not want her parents to know. Criterion variables were the likelihood of
      encouraging her to abstain from sexual activity until she is older, persuading
      her to involve her parents in this decision and prescribing contraceptives
      without notifying her parents. Covariates included physicians' religious,
      demographic and clinical characteristics. RESULTS: Response rate 66%. Most (94%)
      would provide contraceptives without notifying her parents. Half (47%) would
      encourage her to involve a parent, and half (54%) would advise abstinence until
      she is older. Physicians who frequently attend religious services were more
      likely to encourage her to involve her parents (OR 1.9), and to abstain from sex
      until she is older (OR 4.4) but equally likely to provide the contraceptives.
      CONCLUSIONS: Most obstetrician-gynecologists will provide adolescents with
      contraceptives without notifying their parents.

PMID- 21843692
TI  - Sexual, relationship, contraceptive and personal factors influencing emergency
      contraception use: a qualitative study.
AB  - BACKGROUND: Emergency contraception (EC) has not achieved its abortion reduction
      potential in the United States in part due to nonuse. Understanding use behaviors
      may increase EC promotion. STUDY DESIGN: Interviews were conducted with 30 EC
      users aged 18-35 years. Interviews were analyzed for salient themes using
      ATLAS/ti. We used an analytical framework including personal context (life
      circumstances motivating pregnancy prevention), contraceptive context (knowledge,
      attitudes and experience), sexual context (planned/unplanned intercourse) and
      relationship context. RESULTS: Our sample was primarily college-educated,
      nulliparous, single women. EC users were motivated to prevent pregnancy, but
      unwilling or unable to use contraceptive methods due to ambivalence, fear,
      limited access or difficulty with use. Favorable attitudes toward EC, desire to
      defer pregnancy, infrequent intercourse, partner support of EC and relationship
      instability facilitated EC use. CONCLUSIONS: EC fills an important gap in
      preventing pregnancy for motivated women who struggle with contraceptive use.
      Contextual factors informed women's EC behaviors.

PMID- 21843693
TI  - Perceived racial, socioeconomic and gender discrimination and its impact on
      contraceptive choice.
AB  - BACKGROUND: The study was conducted to determine whether perceived racial,
      economic and gender discrimination has an impact on contraception use and choice
      of method. METHODS: We analyzed the first 2,500 women aged 14-45 years enrolled
      in the Contraceptive CHOICE Project, a prospective cohort study aimed to reduce
      barriers to obtaining long-acting reversible contraception. Items from the
      "Experiences of Discrimination" (EOD) scale measured experienced race-, gender-
      and economic-based discrimination. RESULTS: Overall, 57% of women reported a
      history of discrimination. Thirty-three percent reported gender- or race-based
      discrimination, and 24% reported discrimination attributed to socioeconomic
      status (SES). Prior to study enrollment, women reporting discrimination were more
      likely to report any contraception use (61% vs. 52%, p<.001) but were more likely
      to use less effective methods (e.g., barrier methods, natural family planning or
      withdrawal; 41% vs. 32%, p<.001). In adjusted analyses, gender-, race- or SES
      based discrimination were associated with increased current use of less effective
      methods [adjusted risk ratio (aRR) 1.22, 95% confidence interval (CI) 1.06-1.41;
      aRR 1.25, CI 1.08-1.45; aRR 1.23, CI 1.06-1.43, respectively]. After enrollment,
      66% of women with a history of experience of discrimination chose a long-acting
      reversible contraceptive method (intrauterine device or implantable) and 35%
      chose a depo-medroxyprogesterone acetate or contraceptive pill, patch or ring.
      CONCLUSIONS: Discrimination negatively impacts a woman's use of contraception.
      However, after financial and structural barriers to contraceptive use were
      eliminated, women with EOD overwhelmingly selected effective methods of
      contraception. Future interventions to improve access and utilization of
      contraception should focus on eliminating barriers and targeting interventions
      that encompass race-, gender- and economic-based discrimination.

PMID- 21843694
TI  - Changing depot medroxyprogesterone acetate access at a faith-based institution.
AB  - BACKGROUND: Loyola University Medical Center is a Jesuit faith-based hospital
      that previously offered immediate postpartum depot medroxyprogesterone acetate
      (DMPA) for noncontraceptive indications. STUDY DESIGN: We performed a historical
      cohort study comparing patients aged 25 years or less who received immediate
      postpartum DMPA versus women who did not. We used logistic regression to analyze
      associations between patient characteristics and repeat pregnancy within 1 year.
      RESULTS: There was a total of 258 women in our cohort: 105 (40.70%) exposed to
      DMPA. Majorities were non-Caucasian, unmarried, Catholic and received public
      insurance. Multivariable analysis, after adjusting for race and religion, shows a
      statistically significant decrease in repeat pregnancy for patients given
      immediate postpartum DMPA (OR 0.27, 95% CI 0.10-0.72). CONCLUSION: Limits on
      access to DMPA for noncontraceptive indications during the postpartum period
      resulted in significant increases in pregnancy rates for adolescents and young
      adult women at this faith-based institution.

PMID- 21843695
TI  - Oral contraceptive use, iron stores and vascular endothelial function in healthy
      women.
AB  - BACKGROUND: Increased iron stores are associated with greater cardiovascular risk
      in postmenopausal women. Oral contraceptive pill (OCP) use decreases the volume
      of menstrual blood loss and increases iron stores, but the link between OCP use,
      iron stores and cardiovascular risk in premenopausal women has not been
      characterized. STUDY DESIGN: We conducted a cross-sectional study of 23 healthy
      OCP users to determine the association between type and duration of OCP exposure,
      iron stores, and vascular endothelial function [flow-mediated dilation (FMD) in
      the brachial artery]. RESULTS: Median duration of OCP use was 45 months. FMD in
      the brachial artery was significantly associated with progestin type used
      (estranes/gonanes vs. drospirenone) and duration of OCP use (both p<.05) but not
      iron stores. In multivariate analysis, progestin type was the only independent
      predictor of FMD. CONCLUSIONS: Use of OCP containing drospirenone was
      independently associated with greater FMD in the brachial artery and, thus, a
      potentially more favorable cardiovascular risk profile, when compared with use of
      OCP containing estranes/gonanes.

PMID- 21843696
TI  - The effects of condom choice on self-reported condom use among men in Ghana,
      Kenya and South Africa: a randomized trial.
AB  - BACKGROUND: Male condoms are readily available and affordable in many settings,
      but risky sexual acts still go unprotected. STUDY DESIGN: This unblinded
      randomized trial, conducted in Ghana, Kenya and South Africa, was designed to
      assess the impact of providing a choice of condoms on self-reported use and
      uptake over 6 months. RESULTS: We enrolled 1,274 men. The mean subject-specific
      proportion of protected acts with all partners increased from baseline to 6
      months by 0.07 in the control group compared to 0.03 in the choice group
      (p=.025). The observed results were largely consistent across all three
      countries. In the choice group, men clearly preferred one condom type over the
      others, and this preference was consistent across all three countries.
      CONCLUSIONS: Providing one type of male condom in public sector programs appears
      justified. Programs should not focus on the number of brands available, but
      should encourage effective promotion and consistent and correct use of available
      brands.

PMID- 21843697
TI  - Mechanism of action of the Adiana((r)) device: a histologic perspective.
AB  - BACKGROUND: The study was conducted to confirm the mechanism of action of the
      Adiana permanent contraception device by means of histologic analysis of long
      term specimens. STUDY DESIGN: Fifteen specimens were obtained from eight subjects
      undergoing hysterectomy 2 to 4 years after the Adiana procedure. Serial sections
      were stained with hematoxylin and eosin, as well as epithelial membrane antigen
      immunostain. RESULTS: A normal foreign body reaction with minimal chronic
      inflammatory changes was observed in all specimens. Immunostaining for epithelial
      membrane antigen was absent in the interstitial tissue surrounding the matrix.
      CONCLUSION: Histologic analysis of long-term specimens supports the mechanism of
      action of the Adiana permanent contraception device.

PMID- 21843698
TI  - Abstracts of the 2011 North American Forum for Family Planning. Washington, DC,
      USA. October 23-24, 2011.

PMID- 21843699
TI  - Comments to assistant professors Kazim Emre Karasahin and Ugur Keskin.

PMID- 21843700
TI  - Pain and abortion.

PMID- 21843701
TI  - Covered exstrophy with ectopic intestinal tissue and bifid phallus: one-stage
      repair of a complex abnormality.
AB  - Variant presentations of the exstrophy-epispadias complex are rare congenital
      malformations, such as covered exstrophy with bifid phallus. We describe a male
      neonate with covered exstrophy with an intestinal remnant and epispadiac bifid
      phallus. We report this case to emphasize the simultaneous successful repair of
      bifid phallus and exstrophy in this rare complex abnormality.

PMID- 21843702
TI  - Enteric duplication cyst of the pancreas with duplicated pancreatic duct.
AB  - Enteric duplication cyst is one of the rarest forms of cystic lesion of the
      pancreas. We report a unique case of an enteric duplication cyst of the pancreas
      that was communicating with a duplicated pancreatic duct. A 7-year-old girl with
      severe acute abdominal pain was found to have a large cyst that was smoothly
      communicating with the dilated pancreatic duct in the pancreatic tail. Analysis
      of cyst fluid showed elevated levels of amylase, carcinoembryonic antigen (CEA)
      and CA 19-9, and no epithelial cells. Intraoperative cyst pancreatography
      revealed that the pancreatic duct was duplicated in the tail: 1 duct was
      communicating with the cyst, and the other was dilated within the pancreatic
      tail. The patient underwent spleen-preserving distal pancreatectomy and complete
      cyst excision without complication. Because preoperative diagnosis of duplication
      cyst of the pancreas is difficult, this condition should be considered during
      differential diagnosis of atypical cystic lesions of the pancreas. Complete
      excision is desirable for the management of duplication cyst of the pancreas.

PMID- 21843703
TI  - Central pancreatectomy for pancreatoblastoma in a 16-year-old girl.
AB  - Long-term functional results after standard pancreatic resections are a major
      concern, especially in children. An alternative pancreas-sparing procedure (such
      as central pancreatectomy) should be taken into consideration whenever it is
      feasible, and a prolonged survival is expected. Pancreatoblastoma is an unusual
      malignant tumor in childhood. However, in initially resectable tumors, the 15
      year survival is more than 80%. Thus, there is a potential role of a conservative
      pancreatic resection in successful treatment of pancreatoblastoma. The management
      in a case of a 16-year-old girl with a pancreatoblastoma in the body of pancreas
      is presented. Complete surgical resection by central pancreatectomy followed by
      chemotherapy led to a prolonged disease-free survival, with good functional
      results. Central pancreatectomy could be an alternative surgical technique in
      some selected cases of pancreatoblastoma, having the lowest incidence of
      postoperative exocrine and endocrine insufficiency rate and offering the best
      nutritional status.

PMID- 21843704
TI  - Multiple hepatic mesenchymal hamartomas in a premature associated with placental
      mesenchymal dysplasia.
AB  - Placental mesenchymal dysplasia (PMD) is an uncommon disorder that has to be
      differentiated histologically from a partial mole. In contrast to a hydatitiform
      mole, PMD can coexist with a viable fetus. Placental mesenchymal dysplasia is
      characterized by placentomegaly and dilatation of the chorionic vessels. In our
      case, multiple hepatic mesenchymal hamartomas in a preterm were associated with
      PMD. This association is an extremely rare anomaly. Mesenchymal hamartomas occur
      in 5% of all primary liver tumors in children and are generally benign lesions.

PMID- 21843705
TI  - Pseudoangiomatous stromal hyperplasia of the breast in a 10-year-old girl.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion,
      characterized by a dense proliferation of stromal mesenchymal cells of
      myofibroblastic origin forming empty, slitlike channels. The development of PASH
      is subject to hormonal influence and is most commonly seen in premenopausal
      women. In adolescent patients, PASH is rarely reported. Here we report a case of
      PASH presenting in a 10-year-old girl. After the presentation and inconclusive
      radiographic findings, incisional biopsy revealed a soft nodule with
      histopathologic features characteristic of PASH. Immunoperoxidase studies showed
      positive immunoreactivity for CD34 and bcl-2 and negative immunoreactivity for
      CD31 and desmin, supporting the diagnosis of PASH. Because of the benign nature
      of the lesion, excisional biopsy was deferred to minimize damage to the patient's
      developing breast. To our knowledge, this case represents the youngest female
      patient with unequivocal PASH in reported literature.

PMID- 21843706
TI  - Clinical management of cervical ectopic thymus in children.
AB  - OBJECTIVE: Cervical ectopic thymus (CET) is an extremely uncommon etiology of a
      neck mass in an infant. The aim of this study was to study and analyze the
      clinical manifestations, management principles, and pathological diagnosis of
      CET. METHODS: From 1995 to 2010, a total of 25,237 cases of head and neck lesions
      were treated in the Department of Oral and Maxillofacial Surgery, Shanghai Ninth
      People's Hospital. Among these huge numbers of lesions, there were only 3 cases
      of pathological-diagnosed CET presenting as neck masses. These 3 rare cases were
      interesting, and here, we report their clinical management and pathological
      diagnosis. RESULT: Three patients had a pathological diagnosis of CET. Their ages
      ranged from 4 months to 4 years. Clinically, all 3 patients presented with a
      painless neck mass and received surgical resection. Pathological diagnoses are
      based on hematoxylin and eosin and immunohistochemical staining. CONCLUSION:
      Painless swelling or neck mass is the major complaint for CET. Radiologic imaging
      can help determine the extent of the mass and relationship with adjacent
      structures. Surgery with frozen section remains the main method for pathological
      diagnosis and management.

PMID- 21843707
TI  - Gracilis transposition flap for repair of an acquired rectovaginal fistula in a
      pediatric patient.
AB  - Acquired rectovaginal fistulas in the pediatric population are relatively rare
      but are often difficult to treat. We describe a young girl who acquired a
      neorectovaginal fistula after a repeat pull-through procedure for Hirschsprung's
      disease. Durable repair of the fistula was accomplished with a gracilis
      transposition flap, providing a well-vascularized muscle buttress between the
      neorectum and vagina. To our knowledge, this is the first report of a gracilis
      flap in a pediatric patient with an acquired fistula and should be considered for
      this complication after pull-through for Hirschsprung's as well as for other
      perineal fistulas such as those acquired after trauma, infection, or in the
      setting of inflammatory bowel disease.

PMID- 21843708
TI  - Volvulus of the appendix: a case report.
AB  - Volvulus of the appendix is an uncommon phenomenon in children (J Can Med
      Assoc.1966;95:926-927). Only a few reports exist in the literature concerning
      this subject. We describe a 2-year-old child who presented with right lower
      quadrant abdominal pain and was initially diagnosed as ruptured appendicitis with
      abscess. Attempt at computed tomography-guided drainage failed to produce
      purulent drainage, and the child was taken to the operating room for diagnostic
      laparoscopy. Operative findings revealed a volvulus of the appendix, and a
      laparoscopic appendectomy was performed.

PMID- 21843709
TI  - Perineal mass protrusion with rectal mucosa: a rectal duplication that underwent
      exstrophy.
AB  - We present a rare case of a male neonate with a perineal mass with rectal mucosa,
      diagnosed as an exstrophic duplication of the rectum. It was accompanied by a
      cord that was deeply invested in the pelvic diaphragm and was composed of smooth
      muscle, fibrous tissue, and some rectal glands. The association of exstrophic
      rectal duplication with a bifid scrotum, hypospadias, and normal anus has not
      been described previously in the literature.

PMID- 21843710
TI  - Malignant peripheral nerve sheath tumor of the vagus nerve in a teenager with the
      neurofibromatosis 1 gene mutation: a case report.
AB  - Malignant peripheral nerve sheath tumors account for approximately 5% to 10% of
      all soft tissue sarcomas in which 25% to 50% are diagnosed in patients with
      neurofibromatosis 1 (NF1). Tumors are often located in the proximal portion of
      the upper and lower extremities and trunk, whereas cervical vagus nerve
      localizations are extremely rare, and the English literature is limited to
      isolated case reports. Malignant peripheral nerve sheath tumors usually affect
      adults. However, earlier presentation is described in patients with the NF1
      mutation. The authors describe a very rare case of malignant peripheral nerve
      sheath tumor of the vagus nerve in a teenage patient with NF1 focusing on
      surgical management of this uncommon pathology and its histopathologic features
      to underline the importance of differential diagnosis and early treatment of this
      rare and aggressive tumor.

PMID- 21843711
TI  - Necrotizing enterocolitis requiring surgery: outcomes by intestinal location of
      disease in 4371 infants.
AB  - OBJECTIVE: The objective of this study was to determine whether the outcomes of
      infants with surgically managed necrotizing enterocolitis (NEC) differ according
      to whether the location of NEC is in the small bowel, large bowel, or both. STUDY
      DESIGN: A retrospective analysis was performed using the Healthcare Cost and
      Utilization Project Nationwide Inpatient Sample and Kids' Inpatient Database. A
      total of 5374 infants identified as having undergone surgical management of NEC
      were stratified by location of bowel affected as small bowel (SB) only, large
      bowel (LB) only, or both small and large bowel (SB&LB). The type of surgical
      operation performed was used as a proxy for the location of bowel affected.
      RESULTS: Of the 5374 infants with a diagnosis of NEC, 4371 had an operation that
      allowed for stratification by location. The LB group (n = 963) fared the best in
      all outcomes. The SB group (n = 2126) had the longest length of stay and highest
      total hospital charges, and mortality was comparable with that of the SB&LB group
      (n = 1282). CONCLUSIONS: Mortality, length of stay, and total hospital charges
      varied according to location of bowel affected by NEC.

PMID- 21843712
TI  - Comparison of the efficacy of serum amyloid A, C-reactive protein, and
      procalcitonin in the diagnosis and follow-up of necrotizing enterocolitis in
      premature infants.
AB  - PURPOSE: The aim of this study was to compare the efficacy of serum amyloid A
      (SAA) with that of C-reactive protein (CRP), and procalcitonin (PCT) in diagnosis
      and follow-up of necrotizing enterocolitis (NEC) in preterm infants. METHODS: A
      total of 152 infants were enrolled into this observational study. The infants
      were classified into 3 groups: group 1 (58 infants with NEC and sepsis), group 2
      (54 infants with only sepsis), and group 3 (40 infants with neither sepsis nor
      NEC, or control group). The data including whole blood count, CRP, PCT, SAA, and
      cultures that were obtained at diagnosis (0 hour), at 24 and 48 hours, and at 7
      and 10 days were evaluated. RESULTS: A total of 58 infants had a diagnosis of
      NEC. Mean CRP (7.4 +/- 5.2 mg/dL) and SAA (46.2 +/- 41.3 mg/dL) values of infants
      in group 1 at 0 hour were significantly higher than those in groups 2 and 3.
      Although the area under the curve of CRP was higher at 0 hour in infants with
      NEC, there were no significant differences between groups with respect to the
      areas under the curve of SAA, CRP, and PCT at all measurement times. Levels of
      SAA decreased earlier than CRP and PCT in the follow-up of NEC (mean SAA levels
      were 45.8 +/- 45.2, 21.9 +/- 16.6, 10.1 +/- 8.3, and 7.9 +/- 5.1 mg/dL at
      evaluation times, respectively). Levels of CRP and SAA of infants with NEC stages
      II and III were significantly higher than those with only sepsis and/or NEC stage
      I. CONCLUSIONS: Serum amyloid A, CRP, and PCT all are accurate and reliable
      markers in diagnosis of NEC, in addition to clinical and radiographic findings.
      Higher CRP and SAA levels might indicate advanced stage of NEC. Serial
      measurements of SAA, CRP, and PCT, either alone or in combination, can be used
      safely in the diagnosis and follow-up of NEC.

PMID- 21843713
TI  - Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury
      in newborn rats.
AB  - BACKGROUND/PURPOSE: Necrotizing enterocolitis (NEC) is a major cause of mortality
      in neonates and is associated with a disruption in the protective intestinal
      barrier. The precise cause of NEC is elusive. However, ischemia/reperfusion
      injury of the intestine has been considered a major contributing factor. We
      examined the role of Y-27632, a selective Rho-kinase inhibitor, on a
      hypoxia/reoxygenation (H/R)-induced intestinal injury of newborn rat pups.
      METHODS: Hypoxia/reoxygenation was achieved by placing rat pups in an airtight
      chamber aerated with 95% N(2) + 5% CO(2) for 10 minutes followed by 10-minute
      100% oxygen. Forty newborn rat pups were randomly allocated into 4 groups. Group
      1 served as untreated controls. The pups in group 2 were subjected to H/R only.
      In groups 3 and 4, the rats were treated with intraperitoneal injection of 0.3
      and 3 mg kg(-1) day(-1) of Y-27632 for 5 days following H/R, respectively. The
      pups were killed 6 days following the H/R injury. Intestine specimens were
      evaluated for histopathology and biochemical investigation. RESULTS: The
      microscopic lesions in H/R rat pups were virtually the same as those seen in
      neonatal NEC, with severe destruction of villi and crypts. Hypoxia/reoxygenation
      resulted in significant elevation in malondialdehyde levels, but decreased tissue
      nitric oxide levels (P < .05). Protective effects of Y-27632 on H/R-induced
      intestinal injury of newborn rat pups were observed with a significant decrease
      in the intestinal injury score, suppression in malondialdehyde levels, and
      increase in nitric oxide levels (P < .05). CONCLUSIONS: In this experimental
      study, Y-27632 significantly attenuated H/R-induced intestinal injury. These
      findings indicate that inhibition of Rho-kinase may offer a novel therapeutic
      approach in the treatment of NEC.

PMID- 21843714
TI  - Intestinal involvement during 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced
      chronic liver injury in a mouse model.
AB  - PURPOSE: Although a physiologic relationship between intestinal mucosal integrity
      and hepatic function has been previously described, the effect of primary liver
      disease on intestinal mucosal homeostasis has not been previously well
      documented. In the current study, we studied the effects of chronic liver injury
      as a primary injury on enterocyte turnover (proliferation and apoptosis) in a
      mouse model. METHODS: The liver toxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine
      (DDC)-enriched diet was used to induce chronic cholestatic liver injury in mice.
      Livers and intestine were harvested after 3 weeks of dietary treatment of
      histologic analysis and a determination of cell proliferation
      (immunohistochemistry for Ki67), or apoptosis (immunohistochemistry for caspase
      3), as well as a determination of Wnt/beta-catenin signaling activity. RESULTS:
      All DDC-fed animals exhibited histologic evidence of liver damage that was
      associated with the expansion of atypical ductal proliferation near the
      periportal areas and increased oxidative stress. In the intestine, DDC-induced
      liver damage was associated with decreased villus height, decreased enterocyte
      proliferation, and increased cell apoptosis compared with control animals. There
      was also evidence for decreased beta-catenin expression by immunostaining in
      crypt and villus cells of DDC-fed mice compared with control animals. CONCLUSION:
      Primary liver injury and cholestasis is associated with intestinal mucosal
      hypoplasia. Decreased cell proliferation and increased cell apoptosis may be
      responsible for decreased intestinal epithelial cell mass. The observed decrease
      in cell turnover is accompanied by an alteration in Wnt/beta-catenin signaling.

PMID- 21843715
TI  - Congenital biliary dilatation may consist of 2 disease entities.
AB  - BACKGROUND/PURPOSE: This study aims to establish the possible mechanisms of
      pathogenesis of congenital biliary dilatation and to classify the disease
      accordingly. METHODS: Radiologic features of congenital biliary dilatation and
      pancreaticobiliary malunion in 107 affected children were examined and correlated
      with laboratory results. Relative lengths/diameters were calculated to provide
      comparison between children of different ages. Intraluminal pressures of common
      bile duct (CBD) were measured intraoperatively. RESULTS: The minimal relative
      diameters of distal CBD negatively correlated with the maximal relative
      diameters/lengths of dilated CBD, the maximal relative diameters of common
      hepatic duct, and left/right hepatic ducts. The intraluminal pressure in patients
      with a stenotic distal CBD (stenotic group) was significantly higher than that in
      patients with a nonstenotic distal CBD (nonstenotic group). The narrower the
      distal CBD, the more deranged the liver function. Conversely, serum/bile amylase
      levels were more elevated in the nonstenotic group. Common channel protein plugs
      were only found in the nonstenotic group, whereas common hepatic duct strictures,
      intrahepatic duct dilatations, and calculi were detected more frequently in the
      stenotic group. CONCLUSION: We propose to categorize congenital biliary
      dilatation into 2 subgroups: (1) cystic type with stenotic distal CBD associated
      with deranged liver function and common hepatic duct stricture and (2) fusiform
      type with nonstenotic distal CBD associated with pancreatitis and common channel
      protein plugs. Different underlying pathologies of each group require different
      operative strategies.

PMID- 21843716
TI  - Preventive antireflux surgery in neonates with congenital diaphragmatic hernia: a
      single-blinded prospective study.
AB  - OBJECTIVE: Congenital diaphragmatic hernia (CDH) is known to be a predisposing
      factor in gastroesophageal reflux (GER) leading to pulmonary and nutritional
      problems. The aim of this prospective, randomized, patient-blinded study was to
      evaluate the benefit of antireflux surgery at the time of CDH repair. METHODS:
      From 2003 to 2009, 79 neonates with left-sided CDH were included. Forty-three had
      regular hernia closure. Thirty-six patients additionally had fundoplication at
      hernia repair. Follow-up was at 6, 12, and 24 months after birth with a
      standardized questionnaire and a thorax radiograph. Patients with clinical signs
      for GER were evaluated with upper gastrointestinal series and 24-hour pH-metry.
      RESULTS: Seventy-nine of 263 patients participated in this prospective trial.
      Survival rate was 88.61%. The GER symptoms were almost significantly more
      frequent in the group without concomitant fundoplication at the age of 6 months.
      At 24 months, the difference between both groups was not significant anymore.
      Development of body weight in the first 2 years of life was similar in both
      groups. No complications related to initial antireflux surgery were noted.
      CONCLUSION: Patients profit from fundoplication at CDH repair only within the
      first year of life. At the present point of this study, simultaneous
      fundoplication at the time of primary CDH repair cannot be recommended as a
      standard procedure in all patients with left-sided CDH.

PMID- 21843717
TI  - Nitric oxide activity through guanylate cyclase and phosphodiesterase modulation
      is impaired in fetal lambs with congenital diaphragmatic hernia.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with pulmonary
      hypertension and death. Administration of nitric oxide (NO) alone remains
      ineffective in CDH cases. We investigated in near full-term lambs with and
      without CDH the role of guanylate cyclase (GC), the enzyme activated by NO in
      increasing cyclic 3'-5'-guanylosine monophosphate, and the role of
      phosphodiesterase (PDE) 5, the enzyme-degrading cyclic 3'-5'-guanylosine
      monophosphate. METHODS: Congenital diaphragmatic hernia was surgically created in
      fetal lambs at 85 days of gestation. Pulmonary hemodynamics were assessed by
      means of pressure and blood flow catheters (135 days). In vitro, we tested drugs
      on rings of isolated pulmonary vessels. RESULTS: In vivo, sodium nitroprusside, a
      direct NO donor, and methyl-2(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2
      pyridinylmethoxy)-4-(3,4,5 trimethoxyphenyl)-3-isoquinoline carboxylate sulfate
      (T-1032) and Zaprinast, both PDE 5 blockers, reduced pulmonary vascular
      resistance in CDH and non-CDH animals. The activation of GC by sodium
      nitroprusside and the inhibition of PDE 5 by T-1032 were less effective in CDH
      animals. In vitro, the stimulation of GC by 3(5'hydroxymethyl-2'furyl)-1-benzyl
      indazole (YC-1) (a benzyl indazole derivative) and the inhibition of PDE 5 by T
      1032 were less effective in pulmonary vascular rings from CDH animals. The YC-1
      induced vasodilation in rings from CDH animals was higher when associated with
      the PDE 5 inhibitor T-1032. CONCLUSIONS: Guanylate cyclase and PDE 5 play a role
      in controlling pulmonary vascular tone in fetal lambs with or without CDH. Both
      enzymes seem to be impaired in fetal lambs with CDH.

PMID- 21843718
TI  - The utility of computed tomography in the management of patients with spontaneous
      pneumothorax.
AB  - BACKGROUND: Spontaneous pneumothorax may result from rupture of subpleural blebs.
      Computed tomography (CT) has been used to identify blebs to serve as an
      indication for thoracoscopy. We reviewed our experience with spontaneous
      pneumothorax to assess the utility of CT in these patients. METHODS: A
      retrospective review was conducted of all patients who underwent an operation for
      spontaneous pneumothorax from January 1999 to October 2009. All procedures were
      performed thoracoscopically. RESULTS: We identified 39 pneumothoraces in 34
      patients who underwent evaluation and a procedure for spontaneous pneumothorax.
      Mean age was 16.1 years (range, 10-23 years), with an average of 1.7 spontaneous
      pneumothoraces before operation (range, 1-4). Preoperative chest CT scans were
      obtained in 26 cases. Blebs were demonstrated on 8 CT scans. The presence of
      blebs was confirmed at operation in all 8 patients. Of the 18 negative scans, 14
      (77.8%) were found to have blebs intraoperatively, 7 of these patients were
      initially managed nonoperatively and developed recurrence. The sensitivity of CT
      for identifying blebs was 36%. CONCLUSIONS: Chest CT does not appear to be
      precise in the identification of pleural blebs and a negative examination does
      not predict freedom from recurrence. Operative decisions should be based on
      clinical judgment without the use of preoperative CT.

PMID- 21843719
TI  - Clinical features and outcome of physiotherapy in early presenting congenital
      muscular torticollis with severe fibrosis on ultrasonography: a prospective
      study.
AB  - BACKGROUND: It has been reported that ultrasonography (US) can detect the
      severity of congenital muscular torticollis (CMT), and severe fibrosis of the
      sternocleidomastoid (SCM) muscle noted on US is irreversible and likely to
      require surgery. Clinical outcome of CMT depends mainly on the patient's age,
      which is also associated with the severity of fibrosis as determined by US.
      However, there has been no well-designed study to elucidate the true relationship
      among these factors nor a definite consensus on treatment of young infants with
      severe fibrosis in the SCM compared with well-documented reports that late cases
      require surgery. PURPOSE: The purpose of the current study was to investigate
      whether severity of SCM fibrosis on US is correlated with clinical severity and
      outcome of standardized physiotherapy in early presenting CMT. METHODS: Fifty
      patients with a palpable neck mass, initial deficit of passive neck rotation
      (DeltaROT) more than 10 degrees , and age less than 3 months were classified into
      4 US types according to the severity of fibrosis in the SCM and underwent
      standardized physiotherapy and regular assessment. Relationship between US types
      and 2 variables (DeltaROT and treatment duration) and success rate of
      physiotherapy was assessed. RESULTS: None of the cases was classified as type 4.
      Type 3 showed greatest DeltaROT and longest mean treatment duration. Both
      variables showed a significant linear trend of association with US types by P for
      trend (P = .003, P < .001, respectively). Treatment was "successful" in 49
      patients (98%). CONCLUSION: In young infants with CMT, US can document severity;
      and an early and adequate physiotherapy is a good treatment option, particularly
      even in those with severe fibrosis.

PMID- 21843720
TI  - Pediatric genital burns: a 15-year retrospective analysis of outcomes at a level
      1 burn center.
AB  - BACKGROUND/PURPOSE: Burns involving the genitalia and perineum are commonly seen
      in the context of extensive total body surface area (TBSA) burns and rarely as
      isolated injuries because of protection provided by the thighs and the abdomen.
      Genital burns usually result in extended hospital stays and are accompanied by
      severe morbidity and increased mortality. METHODS: A retrospective analysis of
      consecutive pediatric (<18 years) patients with burns involving the genitalia
      admitted to the Saint Barnabas Medical Center Level 1 Burn Unit from January 1,
      1995, to December 31, 2009, was performed. RESULTS: One hundred sixty pediatric
      patients (8.3%) had a genital burn, including 105 patients younger than 5 years
      (65.6%) and 55 patients between 5 and 18 years (34.4%). Overall mean TBSA was
      13.8% +/- 16.8%, mean TBSA (genitalia) was 0.84% +/- 0.25%, mean length of stay
      (LOS) was 11.9 +/- 11.9 days, and mean burn intensive care unit LOS was 4.9 +/-
      9.7 days. CONCLUSIONS: In patients younger than 5 years, a TBSA burn more than
      10% with extensive genitalia involvement is almost always the result of a scald
      injury. Younger patients (<5 years) are more often the victims of abuse, and
      prolonged LOS is the norm (>2 weeks). Patients 5 years or older are more often
      male and usually have a TBSA burn more than 15%.

PMID- 21843721
TI  - Androgen and estrogen receptor expression in the spinal segments of the
      genitofemoral nerve during testicular descent.
AB  - AIM: During testicular descent (TD), the genitofemoral nerve (GFN) is
      masculinized by androgen. This study aimed to test whether androgen receptor
      (AR), estrogen receptor alpha (ERA), or estrogen receptor beta (ERB) are
      expressed during TD in the GFN spinal segments and dorsal root ganglia (DRG) in
      normal and flutamide-treated rats. METHODS: Time-mated Sprague-Dawley dams were
      injected with flutamide (75 mg/kg, subcutaneously (S/C) in sunflower oil) on
      embryonic (E) days 16 to 19. Embryonic and postnatal (P) male L1-2 spinal cord
      segments were collected (E16, E17, E19, P0, P2, and P4) in control and flutamide
      treated groups (n = 5-10). Samples were fixed in 4% paraformaldehyde. Five
      micrometer-thick sections were prepared immunohistochemically for AR, ERA, and
      ERB. RESULTS: During TD, ERB was expressed in L1-2 DRG. Surprisingly, AR was not
      expressed in prenatal DRG, only after P2. There was no ERA expression. Flutamide
      had no effect on AR, ERB, or ERA expression in the L1-2 DRG during TD.
      CONCLUSION: During the E window of androgen sensitivity, the GFN is not directly
      masculinized, with little AR expression and no change with flutamide over this
      period. Estrogen receptor beta is expressed in the DRG during TD. However, its
      relevance is yet to be determined.

PMID- 21843722
TI  - The optimal dose of Adriamycin to create a viable rat model potentially
      applicable to congenital obstructive uropathy.
AB  - PURPOSE: The Adriamycin rat model is an established model for different organ
      anomalies including congenital obstructive uropathy. In the current study, we
      carried out a dose-response analysis to find out the optimal dose of Adriamycin
      to create a viable rat model of obstructive uropathy. METHODS: Thirty time-mated
      Sprague-Dawley rats were divided into 5 groups including 1 control group and 4
      different treatment groups. The 4 Adriamycin dosage regimens investigated in this
      study were 1.25, 1.5, 1.75, and 2 mg/(kg d). Experimental rats (n = 24) were
      injected intraperitoneally with different doses of Adriamycin on gestational days
      7 to 9 (6 rats in each group). Control rats (n = 6) were injected with an
      equivalent volume of saline on the same days. Viable term fetuses were harvested
      on gestational day 21 by cesarean delivery and dissected under a dissecting
      microscope. Serial transverse sections from urinary tract system were obtained
      for histological examination. RESULTS: One hundred thirty-three viable fetuses
      were recovered from Adriamycin-treated rats, and 50 were from rats in the control
      group. There were no resorptions in the control group; however, 52 resorptions
      were recorded in Adriamycin groups. The rates of hydronephrosis and resorptions
      were 60% and 0%, 80.5% and 5.8%, 100% and 17.3%, and 100% and 76.9% at doses of
      1.25, 1.50, 1.75, and 2 mg/(kg d), respectively. Histologic examination of the
      kidneys in the treated groups showed a significant decrease in renal parenchyma
      compared with the control group. CONCLUSIONS: The dosage of 1.5 mg/(kg d) of
      Adriamycin yielded the highest number of viable hydronephrotic fetuses. At this
      dose, urinary abnormalities are milder; but the highest number of viable fetuses
      is provided, which is necessary to create a reproducible and viable animal model.

PMID- 21843723
TI  - Follow-up of acute osteomyelitis in children: the possible role of PET/CT in
      selected cases.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) and/or scintigraphy are commonly
      used for follow-up in children after treatment of acute osteomyelitis. Regularly,
      post-treatment imaging reveals pathological findings even if serum inflammatory
      parameters and clinical presentation are normal. We analyzed combined positron
      emission tomography and multislice computed tomography (PET/CT) for this
      condition. METHODS: Six children received PET/CT after treatment of acute
      osteomyelitis. Post-treatment MRI had revealed suspicious residual and/or
      additional findings. All patients had physiological serum infection parameters
      and no clinical symptoms. RESULTS: Median patient age was 59.5 months (range, 48
      156). No increased 18-Fluor-2-deoxy-D-glucose uptake was observed in 3 patients.
      In 3 patients, there was minimal activity at the site of infection, which,
      however, did not reach the presumed range of osteomyelitis. All children were
      taken off antibiotic medication. No clinical symptoms reoccurred in any of them,
      and repeatedly controlled serum infection parameters were all normal. Median
      follow-up was 33 months (range, 4-65). CONCLUSIONS: The PET/CT was superior to
      MRI in distinguishing between infection and reparative activity within the
      musculoskeletal system in selected children after acute osteomyelitis. The
      termination of antibiotic treatment for children after acute osteomyelitis seems
      justified when laboratory parameters as well as clinical presentation are normal,
      and PET/CT scan is unsuspicious.

PMID- 21843725
TI  - Epidemiology of pediatric cardiac injuries: a National Trauma Data Bank analysis.
AB  - BACKGROUND: Few studies of pediatric cardiac injuries have been conducted in
      large cohorts. We, therefore, investigated the epidemiology of these injuries in
      the United States. METHODS: We identified patients with traumatic cardiac injury
      from the National Trauma Data Bank, using the International Classification of
      Diseases, Ninth Revision, codes. Demographic data, clinical data, and inhospital
      outcomes were compared among 5 age groups. A logistic regression model was used
      to determine adjusted mortality among these groups. RESULTS: Six hundred twenty
      six patients met criteria. Fifty-nine percent sustained cardiac contusion; 36%,
      laceration. Penetrating injuries proved more severe than blunt, having lower
      average Glasgow Coma Scale (6.8 vs 8.7) and higher percentage of patients with
      Glasgow Coma Scale of 8 or lower (68% vs 53%). Associated injuries occurred in
      484 (77%), most common being lung injuries (46%), hemopneumothorax (37%), and rib
      fractures (26%). Eleven percent underwent laparotomy; 9%, thoracotomy; 2%,
      craniotomy/craniectomy; and 0.2%, sternotomy. Complications occurred in 80 (13%),
      most common being cardiac arrest (4%). Firearm injuries result in the highest
      mortality rate (76%), compared with other mechanisms (26%-31%). Crude mortality
      in different age strata showed significant differences that were lost after
      adjustment for confounding variables. CONCLUSIONS: The predominant cardiac injury
      was blunt (65%; 35% sustained penetrating insults), frequently paired with
      contusion. Pediatric cardiac injury is associated with excessive inhospital
      mortality (40%), with no age-related difference in adjusted mortality.

PMID- 21843724
TI  - Mechanism of injury predicts case fatality and functional outcomes in pediatric
      trauma patients: the case for its use in trauma outcomes studies.
AB  - BACKGROUND/PURPOSE: The mechanism of injury (MOI) may serve as a useful adjunct
      to injury scoring systems in pediatric trauma outcomes research. The objective is
      to determine the independent effect of MOI on case fatality and functional
      outcomes in pediatric trauma patients. METHODS: Retrospective review of pediatric
      patients ages 2 to 18 years in the National Trauma Data Bank from 2002 through
      2006 was done. Mechanism of injury was classified by the International
      Classification of Diseases, Ninth Revision, E codes. The main outcome measures
      were mortality, discharge disposition (home vs rehabilitation setting), and
      functional impairment at hospital discharge. Multiple logistic regression was
      used to adjust for injury severity (using the Injury Severity Score and the
      presence of shock upon admission in the emergency department), age, sex, and
      severe head or extremity injury. RESULTS: Thirty-five thousand ninety-seven
      pediatric patients in the National Trauma Data Bank met inclusion criteria. Each
      MOI had differences in the adjusted odds of death or functional disabilities as
      compared with the reference group (fall). The MOI with the greatest risk of death
      was gunshot wounds (odds ratio [OR], 3.52; 95% confidence interval [CI], 2.23
      5.54 95). Pediatric pedestrians struck by a motor vehicle have the highest risk
      of locomotion (OR, 3.30; 95% CI, 2.89-3.77) and expression (OR, 1.65; 95% CI,
      1.22-2.23) disabilities. CONCLUSION: Mechanism of injury is a significant
      predictor of clinical and functional outcomes at discharge for equivalently
      injured patients. These findings have implications for injury prevention,
      staging, and prognosis of traumatic injury and posttreatment planning.

PMID- 21843726
TI  - A preliminary report on the significance of excessively long segment congenital
      hypoganglionosis management during early infancy.
AB  - BACKGROUND/PURPOSE: Excessively long segment of congenital hypoganglionosis is
      rare, and therapeutic strategies to treat this disorder are not well established.
      The purpose of this study is to describe the significance of management in the
      neonatal and early infancy period. PATIENTS AND METHODS: Four patients (aged 1-4
      years) with hypoganglionosis were selected for this study, of which 3 were
      treated at our hospital. In the initial treatment of 3 cases, an intraoperative
      pathological diagnosis was made on the basis of findings from simultaneous
      biopsies taken from the jejunum and sigmoid colon. Retrospective reviews of these
      patients were performed. RESULTS: Initial double-barrel jejunostomy at less than
      50 cm from the ligament of Treitz allowed patients to start oral nutrition within
      a week following surgery. Subsequent refashioning of the initial jejunostomy to
      the Bishop-Koop type was performed at 3 to 6 months of age. Intravenous
      hyperalimentation was required to meet less than 50% of nutritional requirements,
      and patients were able to maintain their body weight within 1.5 SD of the normal
      mean body weight. Liver function test results were also within normal limits in
      the 3 patients treated at our hospital. CONCLUSION: Early diagnosis and treatment
      may help improve the management of patients in the early stages of
      hypoganglionosis.

PMID- 21843727
TI  - Laparoscopically assisted anorectal pull-through for high imperforate anus in
      infants: intermediate results.
AB  - PURPOSE: The aim of this study was to evaluate the clinical outcomes and
      postoperative anal function in infants with congenital high imperforate anus
      treated with laparoscopically assisted anorectal pull-through (LAARP). METHODS:
      From January 2004 to July 2007, 33 patients (28 boys and 5 girls, age ranging
      from 3 to 10 months) with high imperforate anus underwent LAARP. Clinical data of
      the LAARP group were retrospectively compared with those treated by posterior
      sagittal anorectoplasty (PSARP; n = 28) during the same time period. Anorectal
      function of these patients was evaluated using the following 3 methods: the Kelly
      score, anorectal vector volume manometry, and magnetic resonance imaging between
      the ages of 3.1 and 4.4 years. RESULTS: The mean operative time in LAARP and
      PSARP groups was 112.5 +/- 12.4 and 120.4 +/- 18.5 minutes (P > .05),
      respectively. The mean length of hospital stay in the LAARP group was shorter
      than that of PSARP group (11.3 +/- 2.1 vs 14.6 +/- 2.3 days, P < .01). No
      significant difference was observed between LAARP and PSARP groups regarding the
      Kelly score (3.52 +/- 1.42 vs 3.49 +/- 0.82). Although magnetic resonance imaging
      revealed lower malposition rates of rectum in the LAARP group than those of the
      PSARP group at both I-line (3.0% vs 14.3%) and M-line (3.0% vs 10.7%) levels,
      this was not statistically different (P > .05). Compared with the PSARP group,
      lower asymmetric index, larger vector volume, and higher anal canal pressure at
      rest and during voluntary squeeze were observed in LAARP group (P < .05).
      However, there were no significant differences in the length of high-pressure
      zone (15.2 +/- 5.8 vs 15.1 +/- 6.2 mm) and the presence of rectoanal relaxation
      reflex (84.8% vs 85.7%). CONCLUSIONS: Satisfactory fecal continence can be
      achieved in patients with high-type imperforate anus after LAARP.
      Laparoscopically assisted anorectal pull-through has advantages over PSARP,
      including shorter hospital stay and better position of rectum. However, long-term
      follow-up is necessary to compare the benefits of LAARP against PSARP.

PMID- 21843728
TI  - Endosonographic evaluation of anal sphincters in healthy children.
AB  - PURPOSE: To describe the endosonographic anatomy of anal sphincters in healthy
      children and to evaluate the reproducibility of sphincter thickness measurements.
      METHODS: Forty-five healthy children with median age of 3.6 years (range, 1.0
      14.5 years) were studied while under general anesthesia for minor surgery. Anal
      endosonography was performed with a 7- to 10-MHz rotating transducer with a
      diameter of 19 mm. The internal anal sphincter (IAS) and the external anal
      sphincter (EAS) were assessed by 2 independent observers. RESULTS: IAS and EAS
      were identified in all children. The mean thickness of IAS and EAS were 1.3 mm
      and 5.3 mm, respectively. Identification of the inner and outer border of IAS was
      difficult, especially in children younger than 3 years. The thickness of EAS was
      easier to assess, and the interrater reliability for EAS thickness measurements
      was excellent. EAS thickness was positively correlated with the children's age.
      Reflectivity varied within the EAS with frequent hyporeflective areas.
      CONCLUSIONS: Anal endosonography provided visualization of the IAS and EAS in
      children. Assessment of exact IAS thickness was difficult, especially in the
      youngest children. Mean EAS thickness was 5.3 mm, increasing with age.
      Hyporeflective areas of the intact EAS should not be misinterpreted as sphincter
      defects.

PMID- 21843729
TI  - The anomalous clinical anatomy of congenital pouch colon in girls.
AB  - BACKGROUND/PURPOSE: The aim of this study was to evaluate the anomalous clinical
      anatomy of congenital pouch colon (CPC) associated with anorectal agenesis in 22
      consecutive girls managed over a study period of 7 years. METHODS: The 22
      patients were categorized into 2 groups. Group A consisted of 10 patients who
      presented during the neonatal period (n = 9) or as a young infant (n = 1). In
      these patients, only preliminary assessment results were available. Group B (12
      patients) comprised 5 newborns who remained on follow-up and 7 patients who
      presented after the age of 1 year. These 12 patients were assessed and
      investigated in more detail. RESULTS: In group A patients, apart from absence of
      the normal anal opening, the appearance of the external genitalia and perineum
      was essentially normal. Retraction of the labial folds showed radiation of folds
      inward from the margins of the vulval vestibule toward the center, at a point of
      confluence located at a higher level. At laparotomy, the subtypes of CPC were
      type I (n = 4), type II (n = 5), and type III (n = 1). In 8 patients, uterus
      didelphys was present. In all group B patients, the appearance of the external
      genitalia was similar to that in group A patients. However, separate openings of
      the urethra, septate vagina, and vestibular fistula (if present) were visible in
      5 patients, whereas in 3 patients, a single perineal opening was identified. A
      total of 9/12 patients (75%) had urinary incontinence. Examination under
      anesthesia and endoscopy revealed a septate vagina in all 12 patients and an
      open, incompetent bladder neck with reduced bladder capacity in the 9 patients
      with urinary incontinence. The terminal fistula of the colonic pouch opened just
      distal to the bladder neck (n = 1), just posterior and cephalad to the urethral
      opening (n = 2), low in the vestibule (n = 5), and undetermined (n = 4). The
      subtypes of CPC were type I CPC (n = 2), type II CPC (n = 9), and type III CPC (n
      = 1). All 12 patients had uterus didelphys. CONCLUSIONS: The characteristics in
      the anomalous clinical anatomy of CPC in girls, as described here, appear to be
      almost invariable and, especially in regions where CPC is common, should alert
      the clinician to the presence of this malformation.

PMID- 21843730
TI  - The Malone antegrade continence enema procedure: the Amsterdam experience.
AB  - BACKGROUND: The Malone antegrade continence enema (MACE) procedure has been
      previously described as a safe and effective option for the treatment of children
      with chronic defecation disorders when maximal medical therapy and conventional
      treatment have failed. PURPOSE: To evaluate clinical success, complications, and
      quality of life of children with chronic defecation disorders with a MACE stoma.
      METHODS: A retrospective analysis of 23 patients who underwent the construction
      of a MACE stoma was performed. Preoperative and postoperative data were
      evaluated. A specific questionnaire was used to assess patient satisfaction.
      RESULTS: A significant increase was found in defecation frequency (1.0 [range, 0
      4] pretreatment vs 5.5 [range, 0-28] posttreatment per week; P < .006) and a
      significant decrease in fecal incontinence frequency (10 [range, 0-14]
      pretreatment vs 0 [range, 0-14] posttreatment per week; P < .034). Postoperative
      complications of the MACE procedure were fecal leakage (43%), wound infection
      (52%), and stomal stenosis (39%). A total of 86% of the patients were satisfied
      with the results of the Malone stoma (n = 21). CONCLUSIONS: The MACE procedure is
      an effective treatment in children with intractable defecation disorders.
      Postoperative complications are, however, not uncommon. Further refinement of the
      technique focused to reduce the complication rate is necessary to expand the
      application of this approach.

PMID- 21843731
TI  - Laparoscopy and its use in the repair of anorectal malformations.
AB  - INTRODUCTION: Laparoscopy has been used for the treatment of anorectal
      malformations (ARMs) in an attempt to be less invasive and with the hope that it
      would result in a better functional outcome. There remains a significant debate
      about whether these expectations have been fulfilled. METHODS: Seventeen patients
      with ARM for whom laparoscopy was used were retrospectively reviewed. Six were
      operated on primarily by the authors, and 11 cases were referred after a
      laparoscopic repair performed elsewhere. In addition, a literature review was
      performed looking for evidence of less invasiveness and improved functional
      results in patients operated on laparoscopically. RESULTS: The diagnosis was
      imperforate anus with a rectobladder neck fistula in our 6 cases with the fistula
      ligated laparoscopically in each case. In 1 patient, the malformation was
      repaired entirely using laparoscopic technique. The other 5 patients had a
      laparoscopically assisted repair because we had to open the abdomen to taper a
      dilated rectum in 2, mobilize a very high rectum in 2, and take down a distal
      colostomy stoma in 1. Eleven patients were referred with a variety of problems
      after a laparoscopic repair done elsewhere for rectal stricture (5), rectal
      prolapse (4), recurrent rectourethral fistula (3), rectal mislocation (3), failed
      attempted repair leading to fecal incontinence (1), and a posterior urethral
      diverticulum (1). Our literature review included 47 references (involving 323
      patients) published between 1998 and 2010. All studies showed that laparoscopic
      repair of ARMs is feasible. The review, however, did not provide evidence of less
      invasiveness or improved functional results. CONCLUSIONS: Laparoscopy for ARM is
      a less invasive procedure when compared with those operations that would have
      previously required a laparotomy (rectobladder neck fistula). In cases of
      rectoprostatic fistulae, the laparoscopic approach is feasible and avoids a
      lengthy posterior sagittal incision. There is no evidence that the laparoscopic
      approach is a less invasive procedure for other types of ARMs. In cases of
      rectobulbar fistula, congenital anal stenosis, perineal fistula, ARM without
      fistula, the evidence suggests that it may be lead to more complications. There
      is no evidence in the literature demonstrating better functional results in cases
      of ARM operated on laparoscopically.

PMID- 21843732
TI  - Medical management of motility disorders in patients with intestinal failure: a
      focus on necrotizing enterocolitis, gastroschisis, and intestinal atresia.
AB  - BACKGROUND: Intestinal failure (IF) is the dependence upon parenteral nutrition
      to maintain minimal energy requirements for growth and development. It may occur
      secondary to a loss of bowel length, disorders of motility, or both. Short bowel
      syndrome (SBS) is a malabsorptive state resulting from surgical resection,
      congenital defect, or diseases associated with loss of absorptive surface area. A
      particularly vexing problem is associated with whole bowel and/or segmental
      intestinal dysmotility. Motility disorders within the context of SBS and IF may
      relate to rapid intestinal transit secondary to loss of intestinal length,
      dysmotility associated with loss or poor antegrade peristalsis, or gastroparesis.
      Therapy may be classified into medical (prokinetic and antidiarrheal agents) and
      surgical to deal with the overdistended poorly motile bowel. METHODS: We
      performed a systematic review of the literature pertaining to IF, SBS, and
      dysmotility in the pediatric population with gastroschisis, necrotizing
      enterocolitis, and intestinal atresia. In addition to the available treatment
      options, we have provided a review of the literature and a summary of the
      available evidence. CONCLUSION: Despite relatively poor level of evidence
      regarding the application of promotility and antidiarrheal medications in
      patients with SBS and IF, these agents continue to be used. Herein, we provide a
      review of the physiology and pathophysiology of intestinal motility/dysmotility
      and available strategies for the use of promotility and antidiarrheal agents in
      patients with IF/SBS.

PMID- 21843733
TI  - Parapagus conjoined twins with unilateral mesenteric venous outflow.
AB  - This case presents a complication of attempted separation of parapagus conjoined
      twins, related to loss of an intact mesenteric-portal venous axis. Despite known
      lack of a superior mesenteric artery in the right twin, initial evaluation in the
      operating room suggested that separation was possible. After hepatic division,
      however, it became apparent that the mesenteric drainage was not separable; and
      the operation was aborted. Subsequently, significant growth failure and
      hypoglycemia were noted in the right twin. The situation was corrected by
      creating a shunt to reinstitute mesenteric flow to the right twin's liver and
      separating the twin's mesenteric drainage. One year postoperatively, both twins
      are independently nourishing themselves and have been free from hospitalization
      with stable glucoses.

PMID- 21843734
TI  - Esophageal lung: presentation, management, and review of literature.
AB  - Esophageal lung is an extremely rare type of bronchopulmonary foregut
      malformation where a main stem bronchus anomalously arises from the esophagus
      instead of the trachea. Less than 20 cases have been reported, and most of these
      are in association with esophageal atresia. Most cases are treated with
      detachment of the esophageal bronchus with repair of the esophagus and resection
      of the hypoplastic lung. Described herein are the presentation, diagnostic
      workup, and management of 2 such cases of esophageal lung.

PMID- 21843735
TI  - Liver transplantation in a 7-month-old girl with Caroli's disease.
AB  - Caroli's disease (including Caroli's syndrome) is a rare autosomal recessive
      disorder of the liver characterized by diffuse cystic dilatation of the
      intrahepatic bile ducts. The disease may present at any age and is characterized
      by recurrent episodes of biliary obstruction, cholangitis, hepaticolithiasis, and
      liver abscesses. Caroli's syndrome is further associated with congenital hepatic
      fibrosis and portal hypertension. Patients with recurrent complications or
      cirrhosis may die because of recurrent infection, portal hypertension, liver
      failure, or cholangiocarcinoma. Liver transplantation is the treatment of choice
      for these complicated patients. Here we describe the youngest reported patient
      with Caroli's syndrome treated successfully using liver transplantation and
      review the recent literature.

PMID- 21843736
TI  - Traumatic abdominal wall hernia--a case report and literature review.
AB  - We present a case report and comprehensive literature review of pediatric
      traumatic abdominal wall hernia caused by a blow from a bicycle handlebar.
      Traumatic abdominal wall hernia is a rare complication of bicycle handlebar
      injury. An awareness of this entity will help prevent a missed diagnosis.
      Operative repair is met with good outcome.

PMID- 21843737
TI  - Pediatric esophageal leiomyosarcoma: a case report.
AB  - Esophageal leiomyosarcoma accounts for only 0.5% of all esophageal tumors. This
      rare tumor has been reported in middle-aged or elderly patients. In contrast,
      pediatric esophageal leiomyosarcomas have never been reported. The case described
      herein is the first report of an esophageal leiomyosarcoma in a pediatric patient
      with its own characteristics. The patient had symptoms of mild cough without
      dysphagia. The lesion grew rapidly and reached dimensions of 7.0 cm * 5.0 cm *
      6.0 cm in a 3-month period. On computed tomography scan of the chest, the mass
      exhibited mild enhancement after injection of a contrast agent. More evident
      enhancement was found on the 3-minute delayed enhanced computed tomography scan.
      A Phemister operation (transthoracic esophagectomy and esophagogastrostomy) was
      performed on the patient. The patient did not receive adjuvant postoperative
      radiotherapy or chemotherapy. He has been followed for 3 years and is free of
      disease.

PMID- 21843738
TI  - The use of peritoneal venous shunting for intractable neonatal ascites: a short
      case series.
AB  - INTRODUCTION: Intractable ascites in neonates has a varied etiology; and often,
      the cause is idiopathic. The management usually consists of observation,
      diuretics, paracentesis, albumin replacements, and self correction. However, in
      some cases, the above treatment remains unsuccessful. RESULTS: We present 2 cases
      of intractable ascites causing metabolic abnormalities, severe protein and
      immunoglobulin loss, and respiratory compromise. Although the use of
      peritoneovenous shunts for intractable ascites has been reported previously, our
      cases differ in both technique and patient size. Our first patient is an ex-28
      week premature, 1.4-kg infant with intractable ascites for which a peritoneal
      drain was initially placed. After 3 weeks and putting out nearly 300 mL of
      ascitic fluid daily, we placed a peritoneal venous shunt attached to a Medtronic
      pump. A 6.6F Broviac was placed through the Internal Jugular. The Medtronic pump
      was placed subcutaneously on the right chest. The pump was compressed 5 to 10
      times every 8 hours, keeping fluid actively being infused from the belly to the
      vascular system. The second patient was 5 months old, 2.8 kg, with a course
      complicated by necrotizing enterocolitis, prolonged total parenteral nutrition,
      and progressive liver failure and underwent the same procedure. Both patients had
      dramatic responses to the shunting postoperatively, with clinical, radiographic,
      and laboratory evidence of resolution of the ascites. The first patient had the
      shunt removed at 6 months of age and continues to do well, whereas our second
      patient had no recurrence of the ascites, but died about 1 year later from
      cardiopulmonary complications. CONCLUSION: These 2 cases demonstrate that
      peritoneovenous shunting, with the assistance of a Medtronic pump, is an
      effective treatment of intractable neonatal ascites and should be considered
      early in the course before complications develop.

PMID- 21843739
TI  - Communicating esophageal tubular duplication in a newborn infant.
AB  - We describe a communicating esophageal duplication in a newborn infant, without
      any other associated congenital anomalies. The diagnosis of esophageal
      duplication was achieved by a contrast study of the esophagus with diatrizoate
      and computed tomographic scan. Surgical excision of the esophageal duplication
      was carried out. At the 1-year follow-up examination, the patient was doing well.

PMID- 21843740
TI  - A modification of the laparoscopic transcutaneous inguinal hernia repair to
      achieve transfixation ligature of the hernia sac.
AB  - BACKGROUND/PURPOSE: The proposed benefits of laparoscopic inguinal hernia repair
      in the pediatric population include less postoperative pain, smaller scars, and
      easier access to the contralateral groin. This is countered by slightly higher
      recurrence rates reported in some series. These differences are attributable to
      variation in the laparoscopic technique, surgeon experience, and certain anatomic
      features. We describe a modification of the laparoscopic-assisted transcutaneous
      hernia repair that achieves transfixation ligature of the hernia sac and that may
      further reduce recurrence. METHODS: Institutional review board approval was
      obtained, and a retrospective chart review of all patients undergoing repair of
      symptomatic hernias using this new technique was carried out. Data collection
      included demographics, laterality of hernia, operative time, recurrence rate, and
      complications. RESULTS: Twenty-one patients (age 1-144 months) underwent hernia
      repair between October 2009 and October 2010 using a novel technique of
      transcutaneous transfixation ligature of the neck of the hernia sac. The mean
      operative time was 18 minutes (8-35 minutes). Follow-up was from 1 to 12 months.
      There was no intraoperative or postoperative complication and no recurrences to
      date. CONCLUSION: The technique described is a modification of the existing
      laparoscopic-assisted transcutaneous inguinal hernia repair that more closely
      approximates the criterion standard open repair. The technique addresses some
      prevailing concerns with the initially described method of transcutaneous repair,
      and short-term outcomes are positive. Long-term outcomes remain to be defined.

PMID- 21843741
TI  - Urethroplasty and vaginoplasty by a single small bowel interposition graft: a
      novel technique for cloacal reconstruction.
AB  - Despite the advances in surgical management of anorectal malformations, repair of
      cloacal malformations remains a challenging condition for many pediatric
      surgeons. Posterior cloaca is present where urogenital sinus deviates posteriorly
      to form a cloaca with rectum. Often, achieving adequate urethral and vaginal
      length can be challenging. We describe a novel technique where a loop of small
      bowel on a single mesenteric blood supply could be constructed in 2 functional
      tubular structures: one for urethral and the other for vaginal replacement.

PMID- 21843742
TI  - An unusual cause of intestinal obstruction in an infant: phytobezoar within a
      Meckel diverticulum.

PMID- 21843743
TI  - Medico-legal observations concerning a mortal case of granulosa cell tumor of the
      ovary in an 8-month-old infant.

PMID- 21843744
TI  - Demographic correlates of fatigue in the US general population: results from the
      patient-reported outcomes measurement information system (PROMIS) initiative.
AB  - OBJECTIVE: To investigate demographic correlates of fatigue in the US general
      population using a new instrument developed by the Patient-Reported Outcome
      Measurement Information System (PROMIS). First, we examined correlations between
      the new PROMIS instrument and the Functional Assessment of Chronic Illness
      Therapy-Fatigue (FACIT-F) and the SF-36v2 Vitality subscale. Based on prior
      findings, we further examined several demographic correlates of fatigue: whether
      women would report higher levels of fatigue compared to men, and whether married
      people would experience lower levels of fatigue compared to unmarried people. We
      also explored the relationship between age, education, and fatigue. METHODS:
      Analyses were based on fatigue ratings by 666 individuals from the general
      population. Fatigue was assessed with the new PROMIS instrument, the FACIT-F, and
      the SF-36v2 Vitality subscale. Differences in fatigue were examined with
      independent samples t-tests and univariate ANOVAs. RESULTS: The three fatigue
      instruments were highly intercorrelated. Confirming prior reports, women reported
      higher levels of fatigue than men. Married participants reported significantly
      less fatigue than their unmarried counterparts. Univariate ANOVAs yielded a main
      effect for participants' age; younger participants gave significantly higher
      fatigue ratings. We also found a main effect for participants' education.
      Participants with a masters or doctoral degree had significantly lower ratings of
      fatigue than participants with some college education and education up to high
      school. CONCLUSION: Female gender, not being married, younger age and lower
      educational attainment were each associated with increased fatigue in the general
      population and the three fatigue instruments performed equally well in detecting
      the observed associations.

PMID- 21843745
TI  - Measuring disability in patients with chronic fatigue syndrome: reliability and
      validity of the Work and Social Adjustment Scale.
AB  - BACKGROUND: Disability is a defining feature of chronic conditions, and it is an
      increasingly used measure of therapy effectiveness. The Work and Social
      Adjustment Scale (WSAS) is a simple and clear measure of disability. Although the
      scale is widely used, no study has yet investigated its psychometric properties
      in patients with chronic fatigue syndrome (CFS). METHODS: Data from two samples
      of patients were used, one from a multicenter randomized controlled clinical
      trial of treatments for CFS (n =639) and the other from a clinic that specializes
      in CFS (n=384). All patients completed the WSAS as well as other measures.
      RESULTS: Internal consistency and the Spearman-Brown split-half coefficient
      values indicated that the scale is reliable. CFS patients who had comorbid
      diagnoses of depression, anxiety or fibromyalgia had higher WSAS scores. High
      levels of disability were associated with high number of physical symptoms,
      severe fatigue, depression, anxiety, poor sleep quality and poor physical
      fitness, with correlation coefficients ranging between 0.41 and 0.11. Lower
      scores on the WSAS were modestly associated with better physical functioning as
      well as higher levels of physical capacity as assessed by a walking test.
      Sensitivity to change was evaluated in a subgroup of patients who had undergone a
      course of cognitive behavioral therapy. Disability significantly decreased after
      therapy and remained stable at follow-ups. CONCLUSION: The WSAS is a reliable and
      valid assessment tool for disability in patients with CFS.

PMID- 21843746
TI  - Deviations in daily physical activity patterns in patients with the chronic
      fatigue syndrome: a case control study.
AB  - OBJECTIVES: Deviations in daily physical activity patterns may play an important
      role in the development and maintenance of fatigue in the chronic fatigue
      syndrome (CFS). The aim of this study is to gain insight into the objective daily
      physical activity pattern of patients with CFS in comparison with healthy
      controls. The secondary objective is studying the awareness in performing
      physical activities. METHODS: The objective daily physical activity pattern was
      measured with a tri-axial accelerometer in 35 patients with CFS and in 35 age-
      and gender-matched healthy controls. The objective daily physical activity level
      and distribution of physical activities at low, medium and high intensity levels
      during the day were measured. Moreover, variability in performing physical
      activities within and between subjects was computed. Subjective ratings of self
      reported daily physical activity levels were assessed at a visual analog scale.
      RESULTS: CFS patients were significantly less physically active in the afternoon
      and evening, and spent fewer activities at high intensity levels and more at low
      intensity levels. Moreover, CFS patients showed more variability in their own
      physical activity pattern during the afternoon. The heterogeneity in the physical
      activity pattern between subjects within the CFS and control group did not
      differ. Finally, CFS patients were more aware about their daily physical activity
      level than healthy controls. CONCLUSION: CFS patients showed deviations in the
      objectively measured daily physical activity pattern. Future research should
      elucidate the relation between impaired balances in daily physical activity
      patterns and fatigue severity in CFS.

PMID- 21843747
TI  - Higher levels of fatigue are associated with higher CRP levels in disease-free
      breast cancer survivors.
AB  - OBJECTIVE: To investigate the associations between level of fatigue and various
      potential inflammatory biomarkers for fatigue after multivariate adjustments for
      possible confounders in a sample of 299 disease-free survivors of breast cancer
      (BCSs) at a mean of 4 years post diagnosis. METHODS: Medical record data were
      used for cancer-related information, and a follow-up mailed survey collected data
      on fatigue, depression, anxiety and insomnia symptoms as well as information on
      demographics, physical health, medication and lifestyle. Blood samples drawn at
      an outpatient examination were analyzed for leukocyte count, high sensitivity C
      reactive Protein (CRP), interleukin 1 receptor antagonist (IL-1ra), interleukin-6
      (IL-6), soluble tumor necrosis factor receptor type 1 (sTNF-R1) and neopterin.
      RESULTS: Fatigue levels were significantly and positively associated with hsCRP
      (p<.001) and leukocyte count (p=.018), but not with levels of IL-1ra, IL-6, sTNF
      R1 or neopterin in unadjusted analyses. Only hsCRP remained significantly
      associated with fatigue levels in the fully adjusted models (p=.020). Depression
      and self-rated health also remained independently associated with fatigue;
      however these variables were not significantly associated with hsCRP in
      multivariate analyses. CONCLUSION: In general, and after adjustment for potential
      confounders, our hypotheses of positive associations between fatigue and several
      inflammatory markers were not confirmed. However, a small but independent
      association between level of fatigue and hsCRP was observed and supports the
      hypothesis that low-grade inflammation could play a role in the pathogenesis of
      fatigue in BCSs.

PMID- 21843748
TI  - Classification characteristics of the Patient Health Questionnaire-15 for
      screening somatoform disorders in a primary care setting.
AB  - BACKGROUND: This study examines how effectively the Patient Health Questionnaire
      15 (PHQ-15), a self-administered screening instrument, recognizes somatoform
      symptoms and somatoform disorders in a German primary care setting. METHODS: A
      selected sample of 308 patients (mean age 47.2 years, 71.4% women) from two
      regular primary care practices was screened with the PHQ-15 and additionally
      examined with structured interviews. Their primary care physicians rated symptoms
      reported in the interview as either "medically explained" or "medically
      unexplained." RESULTS: Seventy-six percent of the symptoms were judged as
      medically unexplained. The PHQ-15 correlated significantly with the total number
      of symptoms as well as the number of somatoform symptoms (both r=0.63; P<=.001).
      A comparison between the most frequently reported symptoms in the interview and
      the 15 items of the PHQ-15 revealed that even though the PHQ-15 does not
      differentiate between medically explained and medically unexplained symptoms, it
      does catch many somatoform symptoms. When used to predict the diagnosis of a
      somatoform disorder, a cutoff of 10 points in the PHQ-15 was identified as
      optimal, resulting in a sensitivity of 80.2% and specificity of 58.5%. However,
      the cutoff has to be adjusted according to specific research or clinical
      purposes. CONCLUSION: Several previous results could be confirmed, and under
      consideration of some limitations, the PHQ-15 seems to be a valuable tool for
      identifying somatoform symptoms and disorders in primary care.

PMID- 21843749
TI  - A confirmatory factor analysis of the Beck Depression Inventory-II in end-stage
      renal disease patients.
AB  - OBJECTIVE: We sought to examine several competing factor structures of the Beck
      Depression Inventory-II (BDI) in a sample of patients with End-Stage Renal
      Disease (ESRD), in which setting the factor structure is poorly defined, though
      depression symptoms are common. In addition, demographic and clinical correlates
      of the identified factors were examined. METHODS: The BDI was administered to
      clinical sample of 460 ESRD patients attending 4 UK renal centres. Competing
      models of the factor structure of the BDI were evaluated using confirmatory
      factor analysis. RESULTS: The best fitting model consisted of general depression
      factor that accounted for 81% of the common variance between all items along with
      orthogonal cognitive and somatic factors (G-S-C model, CFI=.983, TLI=.979,
      RMSEA=.037), which explained 8% and 9% of the common variance, respectively. Age,
      diabetes, and ethnicity were significantly related to the cognitive factor,
      whereas albumin, dialysis adequacy, and ethnicity were related to the somatic
      factor. No demographic or clinical variable was associated with the general
      factor. CONCLUSION: The general-factor model provides the best fitting and
      conceptually most acceptable interpretation of the BDI. Furthermore, the
      cognitive and somatic factors appear to be related to specific demographic and
      clinical factors.

PMID- 21843750
TI  - The influence of fear of symptoms and perceived control on asthma symptom
      perception.
AB  - OBJECTIVE: Self-reported asthma symptoms correlate only modestly with measures of
      underlying pathophysiological mechanisms. In this study, we investigated the role
      of fear of symptoms and perceived control on respiratory symptom perception in
      patients with asthma. METHODS: Patients with intermittent to moderate persistent
      asthma (N=32) were administered 4 subsequent rebreathing challenges (one using
      100% O(2) and three using 5% CO(2) and 95% O(2)). We manipulated perceived
      control by providing information on the availability/unavailability of rescue
      medication during the challenges (perceived control/no control condition).
      Perceived symptoms and lung function were assessed after each rebreathing
      challenge. RESULTS: Persons with low fear of symptoms reported respiratory
      symptoms to be less unpleasant during the perceived control condition compared to
      the no control condition. The reverse was found for persons with high fear of
      symptoms. The interaction between fear of symptoms and the control manipulations
      was mediated by threat perception. CONCLUSION: Messages intended to increase
      perceived control over symptoms may actually increase threat in persons with high
      fear of symptoms and eventually increase unpleasantness of respiratory
      sensations. This finding underlines the importance of affective processes in the
      perception of asthma symptoms and shows that instructions to patients should take
      pre-existing fear levels into account.

PMID- 21843752
TI  - Quality of life of adolescents with asthma: the role of personality, coping
      strategies, and symptom reporting.
AB  - OBJECTIVE: The aim of this study was to test which personality traits were
      related to quality of life (QOL) of adolescents with asthma, and whether
      relations between personality and QOL were mediated by coping strategies and
      symptom reporting. METHODS: A sample of 405 12 to 16-year-olds with asthma
      completed questionnaires on personality, coping, symptom reporting, and QOL
      (overall QOL and positive effects QOL). The direct relations between personality
      traits and QOL, as well as mediation pathways were tested with structural
      equation modeling. RESULTS: Adolescents high on extraversion and low on
      neuroticism had better overall QOL, while adolescents high on agreeableness had
      better positive-effects QOL. The coping strategy restricted lifestyle fully
      mediated the relation between extraversion and overall QOL, the relation between
      neuroticism and overall QOL was fully mediated by symptom reporting and the
      coping strategy worrying about asthma. The coping strategies positive reappraisal
      and hiding asthma fully mediated the relation between agreeableness and positive
      effects QOL. CONCLUSION: The results show that personality is related to QOL in
      adolescents with asthma. These relations were fully mediated by coping and
      symptom reporting. This study sheds light on the underlying mechanism why
      personality is associated with QOL. The results of this study will help to
      understand what determines QOL in patients with chronic illness in general and
      adolescents with asthma specifically. Furthermore, the results will help to
      design interventions that could facilitate minimizing the negative effects of
      having asthma on the QOL of these adolescents.

PMID- 21843751
TI  - Behavior problems and prevalence of asthma symptoms among Brazilian children.
AB  - OBJECTIVE: Asthma is the most common chronic disease in childhood and has been
      designated a public health problem due to the increase in its prevalence in
      recent decades, the amount of health service expenditure it absorbs and an
      absence of consensus about its etiology. The relationships among psychosocial
      factors and the occurrence, symptomatology, and severity of asthma have recently
      been considered. There is still controversy about the association between asthma
      and a child's mental health, since the pathways through which this relationship
      is established are complex and not well researched. This study aims to
      investigate whether behavior problems are associated with the prevalence of
      asthma symptoms in a large urban center in Latin America. METHODS: It is a cross
      section study of 869 children between 6 and 12 years old, residents of Salvador,
      Brazil. The International Study of Allergy and Asthma in Childhood (ISAAC)
      instrument was used to evaluate prevalence of asthma symptoms. The Child Behavior
      Checklist (CBCL) was employed to evaluate behavioral problems. RESULTS: 19.26%
      (n=212) of the children presented symptoms of asthma. 35% were classified as
      having clinical behavioral problems. Poisson's robust regression model
      demonstrated a statistically significant association between the presence of
      behavioral problems and asthma symptoms occurrence (PR: 1.43; 95% CI: 1.10-1.85).
      CONCLUSION: These results suggest an association between behavioral problems and
      pediatric asthma, and support the inclusion of mental health care in the
      provision of services for asthma morbidity.

PMID- 21843753
TI  - Mental health problems, obstructive lung disease and lung function: findings from
      the general population.
AB  - OBJECTIVE: There is cumulative evidence for a strong association of obstructive
      lung disease, i.e. asthma and COPD, with poor mental health, particularly with
      anxiety disorders and major depression. However, studies relating mental health
      problems to objective measures of lung function as assessed by spirometry are
      lacking. METHODS: The 12-month prevalence of specific psychopathological
      syndromes among 1772 adults from the general population was estimated by a
      structured interview. Additionally, participants underwent spirometry and were
      asked about obstructive lung disease in the year prior to the study. Logistic and
      linear regression models were used to relate obstructive lung disease and
      spirometrically defined airway obstruction to mental health problems. RESULTS:
      Mental health problems were found in 35.7% of the participants. After adjusted
      for sociodemographic, clinical and life-style factors, asthma and chronic
      bronchitis were associated with almost all domains of mental health problems. In
      contrast, independent of its definition, spirometric airflow limitation was only
      related to generalized anxiety (odds ratios ranging from 2.3 to 2.7). A reduced
      ratio of forced expiratory volume in one second to forced vital capacity was
      associated with mental health problems in general and panic and general anxiety
      in particular. CONCLUSION: Our findings suggest an association of objective
      measure of airflow limitation to generalized anxiety and panic. While the causal
      relationship between obstructive lung disease, airflow limitation and anxiety
      remains to be determined, clinicians should pay diagnostic attention to the
      significant overlap of these conditions.

PMID- 21843754
TI  - Physical symptoms 14 months after a natural disaster in individuals with or
      without injury are associated with different types of exposure.
AB  - OBJECTIVE: To investigate whether different types of exposure to the 2004 tsunami
      were associated with physical symptoms 14 months after the disaster and to study
      correlations between survivors' physical and psychological symptoms. METHODS:
      Using a cross-sectional design, 1505 survivors from the 2004 Indian Ocean
      Tsunami, tourists from Stockholm, who had been present in the disaster areas,
      responded to a postal questionnaire. Eight groups based on type of exposure were
      created. Physical symptoms occurring on a daily or weekly basis over the past
      year were investigated in four indices: musculoskeletal, cardiorespiratory,
      neurological, and gastrointestinal. Mental health symptoms (General Health
      Questionnaire-12) and posttraumatic stress symptoms (Impact of Event Scale
      Revised) were also investigated. Multiple logistic regression analyses were
      conducted with controls for background variables and exposure, with physical
      symptoms as outcome variables. The association between physical and psychological
      symptoms was studied with the Spearman Rank Order Correlation. RESULTS: Different
      types of exposure during the disaster were associated with physical symptoms 14
      months later for survivors both with and without severe physical injury. The
      single exposure of life threat, also in combination with other exposures, was
      associated with a higher risk for reporting of physical symptoms. Physical
      symptoms showed modest yet significant correlation with psychological symptoms.
      CONCLUSION: It is important to pay attention to both physical and psychological
      symptoms among disaster survivors whether they have been injured or not. A
      relatively simple questionnaire about physical symptoms may be a good complement
      to the scales used to assess psychological problems after disaster.

PMID- 21843755
TI  - Changes in the coping styles of spouses and the influence of these changes on
      their psychosocial functioning the first year after a patient's stroke.
AB  - OBJECTIVE: The objective of this study was to examine the changes in spouses'
      coping styles that occur in the first year after a patient's stroke and the
      influence of these changes on the spouses' psychosocial functioning. METHODS: A
      total of 211 spouses of patients with stroke were assessed at three different
      time points using self-reported questionnaires (at the time of the patient's
      admission to inpatient rehabilitation, 2 months after discharge and 1 year
      poststroke). We used linear mixed-model and multiple linear regression analyses
      to analyse the data. RESULTS: Spouses' use of an active coping style decreased
      significantly in the first year poststroke. There were no significant overall
      changes in the use of a passive coping style. The use of a passive coping style
      at admission and increases in passive coping style in the first year poststroke
      predicted worse psychosocial functioning 1 year poststroke. The models explained
      between 32% and 50% of the variance in quality of life, depressive symptoms and
      strain. CONCLUSION: The present study indicates that spouses' passive coping
      style is maladaptive poststroke when used in the acute as well as in the chronic
      phase. Use of an active coping style decreases in the first year poststroke, but
      these decreases do not predict psychosocial outcomes.

PMID- 21843756
TI  - Depressive symptoms as a risk factor for the common cold among employees: a 4
      month follow-up study.
AB  - OBJECTIVE: The purpose of this study was to investigate the correlation between
      symptoms of depression in workers and the common cold. METHODS: A follow-up
      survey of workers at 44 small- to medium-sized companies was conducted; 1350
      questionnaires were used in the final analysis. The first survey requested
      information regarding personal information, work characteristics and symptoms of
      depression (Center for Epidemiologic Studies Depression Scale); the second survey
      queried participants who answered the first survey about manifestations of the
      common cold during the previous four months. Odds ratios (ORs) were calculated
      using a logistic regression model, which was adjusted for potential confounders.
      All analyses were stratified according to gender separately. RESULTS: The ORs for
      reporting symptoms of the common cold were 1.36 (95% confidence interval [CI]:
      1.01-1.83) and 2.27 (95% CI: 1.49-3.45) in males and females, respectively. When
      adjusted for age, marital status, educational level, smoking habits, alcohol
      consumption, exercise, sleep duration and job type, the ORs remained significant
      for both genders (male: 1.38; 95% CI: 1.01-1.89; female: 2.08; 95% CI: 1.32
      3.23). CONCLUSIONS: The risk of self-reported manifestations of the common cold
      was higher in workers who reported symptoms of depression.

PMID- 21843757
TI  - For a unified definition of apathy.

PMID- 21843758
TI  - The can-should problem.

PMID- 21843759
TI  - Historical perspectives of The American Association for Thoracic Surgery: Julian
      Johnson (1906-1987).

PMID- 21843760
TI  - Survival after resection of synchronous non-small cell lung cancer.
AB  - OBJECTIVES: Our objective was to determine the long-term survival of patients
      with resected synchronous multiple pulmonary malignant tumors. METHODS: This is a
      multi-institutional retrospective study of patients who underwent surgical
      resection of synchronous (nonbronchioloalveolar) non-small cell lung cancer.
      RESULTS: Between March 1996 and December 2009, 67 patients (30 men) underwent 121
      operations. Forty-four patients had bilateral tumors. Positron emission
      tomographic scans were performed in 58 (87%) patients, computed tomographic scans
      and magnetic resonance imaging of the brain in 53 (79%), and mediastinoscopy in
      56 (84%). N2 lymph nodes were benign in all patients before undergoing resection
      of bilateral tumors of the same histologic type. Types of resection were
      lobectomy in 62, sublobar in 73, and pneumonectomy in 1. Eleven patients (16%)
      had postoperative morbidities. Cancer-specific 3- and 5-year survivals were 73%
      and 69%, respectively, and overall 3- and 5-year survivals were 64% and 53%,
      respectively. Subgroup analysis demonstrated no difference in overall survival at
      5 years between bilateral tumors of the same histologic type (M1a) (49%) versus
      different histologic types 42% (P = .88), or between bilateral tumors (50%) and
      ipsilateral tumors (54%) (P = .83). CONCLUSIONS: The 5-year survival of
      surgically resected, synchronous, N2-negative, nonbronchioloalveolar, non-small
      cell lung cancer is excellent, even in patients who have bilateral lung lesions
      that harbor the same histologic features. Although the new TNM classification
      system labels this disease as clinical stage IV M1a, survival acts more like a
      separate T1 lesion after surgical resection. Thus, surgical resection should be
      considered in appropriately selected patients who have multiple pulmonary
      malignant tumors that are N2 negative.

PMID- 21843762
TI  - Emergency operation for penetrating thoracic trauma in a metropolitan surgical
      service in South Africa.
AB  - INTRODUCTION: This audit examines our total experience with penetrating thoracic
      trauma. It reviews all the patients who were brought alive to our surgical
      service and all who were taken directly to the mortuary. The group of patients
      who underwent emergency operation for penetrating thoracic trauma is examined in
      detail. METHODOLOGY: A prospective trauma registry is maintained by the
      Pietermaritzburg Metropolitan Complex. This database was retrospectively
      interrogated for all patients requiring an emergency thoracic operation for
      penetrating injury from July 2006 till July 2009. A retrospective review of
      mortuary data for the same period was undertaken to identify patients with
      penetrating thoracic trauma who had been taken to the forensic mortuary. RESULTS:
      Over the 3-year period July 2006 to July 2009, a total of 1186 patients, 77 of
      whom were female, were admitted to the surgical services in Pietermaritzburg with
      penetrating thoracic trauma. There were 124 gunshot wounds and 1062 stab wounds.
      A total of 108 (9%) patients required emergency operation during the period under
      review. The mechanism of trauma in the operative group was stab wounds (n = 102),
      gunshot wound (n = 4), stab with compass (n = 1), and impalement by falling on an
      arrow (n = 1). Over the same period 676 persons with penetrating thoracic trauma
      were taken to the mortuary. There were 135 (20%) gunshot wounds of the chest in
      the mortuary cohort. The overall mortality for penetrating thoracic trauma was
      541 (33%) of 1603 for stab wounds and 135 (52%) of 259 for gunshot wounds of the
      chest. Among the 541 subjects with stab wounds from the mortuary cohort, there
      were 206 (38%) with cardiac injuries. In the emergency operation group there were
      11 (10%) deaths. In 76 patients a cardiac injury was identified. The other
      injuries identified were lung parenchyma bleeding (n = 12) intercostal vessels (n
      = 10), great vessels of the chest (n = 6), internal thoracic vessel (n = 2), and
      pericardial injury with no myocardial injury (n = 2). Most patients reached the
      hospital within 60 minutes of sustaining their injury. A subset of 12 patients
      had much longer delays of 12 to 24 hours. Surgical access was via median
      sternotomy in 56 patients and lateral thoracotomy in 52. The overall mortality
      for penetrating cardiac trauma in our series was 217 (76%) of 282. CONCLUSIONS:
      Penetrating thoracic trauma has a high mortality rate of 30% for subjects with
      stab wounds and 52% for those with gunshot wounds. Less than a quarter of
      patients with a penetrating cardiac injury reach the hospital alive. Of those who
      do and who are operated on, about 90 percent will survive. Other injuries
      necessitating emergency operation are lung parenchyma, intercostal vessels and
      internal thoracic vessels, and great vessels of the thorax. Gunshot wounds of the
      thorax remain more lethal than stab wounds.

PMID- 21843763
TI  - Deficiency in comparison of data between mechanical valve studies.

PMID- 21843765
TI  - Late postoperative pericardial effusion.

PMID- 21843768
TI  - Evidence for efficacy of off-pump coronary artery bypass surgery: facts and fads.

PMID- 21843766
TI  - Endocarditis surgery: need for a specific risk scoring system.

PMID- 21843770
TI  - Endoscopic versus open saphenous vein harvest technique in the Randomized On/Off
      Bypass (ROOBY) trial.

PMID- 21843772
TI  - Systems biology and cancer.

PMID- 21843773
TI  - Education, innovation and safe practice in surgical oncology.

PMID- 21843774
TI  - Characterization of positron emission tomography hypoxia tracer uptake and tissue
      oxygenation via electrochemical modeling.
AB  - PURPOSE: Unique uptake and retention mechanisms of positron emission tomography
      (PET) hypoxia tracers make in vivo comparison between them challenging.
      Differences in imaged uptake of two common hypoxia radiotracers, [(61)Cu]Cu-ATSM
      and [(18)F]FMISO, were characterized via computational modeling to address these
      challenges. MATERIALS AND METHODS: An electrochemical formalism describing
      bioreductive retention mechanisms of these tracers under steady-state conditions
      was adopted to relate time-averaged activity concentration to tissue partial
      oxygen tension (PO(2)), a common metric of hypoxia. Chemical equilibrium
      constants of product concentration to reactant concentration ratios were
      determined from free energy changes and reduction potentials of pertinent
      reactions reported in the literature. Resulting transformation functions between
      tracer uptake and PO(2) were compared against measured values in preclinical
      models. Additionally, calculated PO(2) distributions from imaged Cu-ATSM tracer
      activity concentrations of 12 head and neck squamous cell carcinoma (HNSCC)
      patients were validated against microelectrode PO(2) measurements in 69 HNSCC
      patients. RESULTS: Both Cu-ASTM- and FMISO-modeled PO(2) transformation functions
      were in agreement with preclinical measured values within single-deviation
      confidence intervals. High correlation (r(2)=0.94, P<.05) was achieved between
      modeled PO(2) distributions and measured distributions in the patient
      populations. On average, microelectrode hypoxia thresholds (2.5 and 5.0 mmHg)
      corresponded to higher Cu-ATSM uptake [2.5 and 2.0 standardized uptake value
      (SUV)] and lower FMISO uptake (2.0 and 1.4 SUV). Uncertainties in the models were
      dominated by variations in the estimated specific activity and intracellular
      acidity. CONCLUSIONS: Results indicated that the high dynamic range of Cu-ATSM
      uptake was representative of a narrow range of low oxygen tension whose values
      were dependent on microenvironment acidity, while FMISO uptake was representative
      of a wide range of PO(2) values that were independent of acidity. The models shed
      light on possible causes of these discrepancies, particularly as it pertains to
      image contrast, and may prove to be a useful methodology in quantifying
      relationships between other hypoxia tracers. Comprehensive and robust assessment
      of tumor hypoxia prior to as well as in response to therapy may be best provided
      by imaging of multiple hypoxia markers that provide complementary rather than
      interchangeable information.

PMID- 21843775
TI  - Complementary information from magnetic resonance imaging and (18)F
      fluoromisonidazole positron emission tomography in the assessment of the response
      to an antiangiogenic treatment in a rat brain tumor model.
AB  - INTRODUCTION: No direct proof has been brought to light in a link between hypoxic
      changes in glioma models and the effects of antiangiogenic treatments. Here, we
      assessed the sensitivity of the detection of hypoxia through the use of (18)F
      fluoromisonidazole positron emission tomography ([(18)F]-FMISO PET) in response
      to the evolution of the tumor and its vasculature. METHODS: Orthotopic glioma
      tumors were induced in rats after implantation of C6 or 9L cells. Sunitinib was
      administered from day (D) 17 to D24. At D17 and D24, multiparametric magnetic
      resonance imaging was performed to characterize tumor growth and vasculature.
      Hypoxia was assessed by [(18)F]-FMISO PET. RESULTS: We showed that brain hypoxic
      volumes are related to glioma volume and its vasculature and that an
      antiangiogenic treatment, leading to an increase in cerebral blood volume and a
      decrease in vessel permeability, is accompanied by a decrease in the degree of
      hypoxia. CONCLUSIONS: We propose that [(18)F]-FMISO PET and multiparametric
      magnetic resonance imaging are pertinent complementary tools in the evaluation of
      the effects of an antiangiogenic treatment in glioma.

PMID- 21843777
TI  - Postreperfusion myocardial technetium-99m-sestamibi defect corresponds to area at
      risk: experimental results from an ischemia-reperfusion porcine model.
AB  - INTRODUCTION: Technetium-99m-sestamibi (MIBI) is the most frequently used
      myocardial perfusion tracer in patients with ischemic heart disease. In patients
      with acute ST-elevation myocardial infarction, we previously found that the
      defect in myocardial MIBI uptake was the same in patients injected with MIBI
      before primary angioplasty and in patients injected immediately after successful
      treatment. Thus, reperfusion may not be followed by increased uptake of MIBI.
      Instead, the MIBI defect after reperfusion may reflect the area at risk (AAR)
      defined by MIBI injected before treatment. We intended to investigate whether
      myocardial imaging with MIBI administered after reperfusion reflects myocardial
      perfusion or rather the ischemic AAR. METHODS: In 12 pigs, left anterior
      descending coronary artery was totally occluded for 45 min with an angioplasty
      balloon. After a 2-h reperfusion, MIBI was injected intravenously, and (153)Gd
      microspheres were injected in left atrium. AAR and infarct size (IS) were
      determined by histochemical staining. MIBI and microsphere distribution were
      evaluated by counting the sliced left ventricle on a gamma camera. Defects were
      defined as uptake less than 45% of maximum uptake. RESULTS: The mean+/-S.D.
      defect size as a fraction of left ventricle was for MIBI 21%+/-5.5%, AAR 25%+/
      6.3%, IS 13%+/-3.9% and microspheres defect size 7.3%+/-5.5%. MIBI defect size
      overestimated IS (P=.0005) and microspheres defect size (P=.0001), but it was not
      significantly different from AAR (P=.30). CONCLUSION: In a porcine model of
      myocardial infarction after 45 min of ischemia, MIBI administered 120 min after
      reperfusion delineates AAR.

PMID- 21843776
TI  - A (99m)Tc-labeled dual-domain cytokine ligand for imaging of inflammation.
AB  - INTRODUCTION: Interleukin (IL)-1 and IL-18 are potent proinflammatory cytokines
      in inflammation-related diseases. Their actions are regulated by IL-1 receptor
      antagonist (IL-1ra) and IL-18 binding protein (IL-18bp). This study was designed
      to (99m)Tc-radiolabel an IL-1ra and IL-18bp dual-domain cytokine ligand, IL-18bp
      Fc-IL-1ra, for specific inflammation targeting. METHODS: The (99m)Tc-IL-18bp-Fc
      IL-1ra was obtained by direct labeling via 2-iminothiolane reduction. Competitive
      binding of (99m)Tc-labeled and unlabeled IL-18bp-Fc-IL-1ra to rat
      polymorphonuclear leukocytes was assessed in vitro. A mouse ear edema model was
      used to evaluate specific targeting properties of (99m)Tc-IL-18bp-Fc-IL1ra in
      vivo. The correlation between (99m)Tc-IL-18bp-Fc-IL-1ra uptake and (111)In
      labeled polymorphonuclear neutrophil infiltration was studied using ischemic
      reperfused rat hearts. RESULTS: Direct (99m)Tc-labeling yielded a stable dual
      domain cytokine radioligand with radiochemical purity greater than 95% after gel
      filtration. Competitive binding studies showed specific targeting of (99m)Tc-IL
      18bp-Fc-IL-1ra to inflammatory cells. The (99m)Tc-IL-18bp-Fc-IL-1ra uptake was
      1.80+/-0.17 % injected dose per gram (%ID/g) in the inflamed ear without
      blocking, whereas uptake in the presence of IL-18bp-Fc-IL-1ra was 1.09+/-0.08
      %ID/g (P<.05). The amounts of IL-1beta and IL-18 were significantly increased in
      the inflamed ears compared to the vehicle controls. A significant correlation of
      (99m)Tc-IL-18bp-Fc-IL-1ra with (111)In-labeled neutrophil distribution was
      observed in the ischemic-reperfused hearts (P<.001). CONCLUSION: Targeting
      proinflammatory cytokines with (99m)Tc-IL-18bp-Fc-IL-1ra may provide a suitable
      approach for specific detection of inflammatory sites.

PMID- 21843778
TI  - Distribution of adoptively transferred porcine T-lymphoblasts tracked by (18)F-2
      fluoro-2-deoxy-D-glucose and position emission tomography.
AB  - INTRODUCTION: Autologous or allogeneic transfer of tumor-infiltrating T
      lymphocytes is a promising treatment for metastatic cancers, but a major concern
      is the difficulty in evaluating cell trafficking and distribution in adoptive
      cell therapy. This study presents a method of tracking transfusion of T
      lymphoblasts in a porcine model by (18)F-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG)
      and positron emission tomography. METHODS: T-lymphoblasts were labeled with the
      positron-emitting tracer [(18)F]FDG through incubation. The T-lymphoblasts were
      administered into the bloodstream, and the distribution was followed by positron
      emission tomography for 120 min. The cells were administered either intravenously
      into the internal jugular vein (n=5) or intraarterially into the ascending aorta
      (n=1). Two of the pigs given intravenous administration were pretreated with low
      molecular-weight dextran sulphate. RESULTS: The cellular kinetics and
      distribution were readily quantifiable for up to 120 min. High (78.6% of the
      administered cells) heterogeneous pulmonary uptake was found after completed
      intravenous transfusion. The pulmonary uptake was decreased either by
      preincubating and coadministrating the T-lymphoblasts with low-molecular-weight
      dextran sulphate or by administrating them intraarterially. CONCLUSIONS: The
      present work shows the feasibility of quantitatively monitoring and evaluating
      cell trafficking and distribution following administration of [(18)F]FDG-labeled
      T-lymphoblasts. The protocol can potentially be transferred to the clinical
      setting with few modifications.

PMID- 21843779
TI  - Simplified quantification of FDG metabolism in tumors using the autoradiographic
      method is less dependent on the acquisition time than SUV.
AB  - The standard uptake value (SUV) is the most often used semi-quantitative measure
      of (18)F-fluorodeoxyglucose (FDG) uptake. We tested the hypothesis that the
      autoradiographic method with a population-based input curve yields an
      approximation of FDG metabolism represented by the flux value Ki, which is less
      dependent on the acquisition time point than SUV. METHODS: We analyzed 20
      patients with chest tumors (16 males, age 65+/-10 years). After injection of 350
      MBq FDG using the INTEGO PET infusion system, a series of 35 scans of 10- to 300
      s duration were acquired until 45 min. FDG flux was calculated using the Patlak
      method (Ki(patlak)) and also quantified with the autoradiographic method using
      the last acquisition only and the individual image-derived input function
      (Ki(autoreal)), as well as with a population-based input function (Ki(autonorm)).
      In a simulation study, the time courses of tumor SUV, tumor-to-blood ratio and
      tumor Ki values were calculated from 30 to 90 min. RESULTS: The FDG flux values
      (Ki) of the different tumors, obtained with the autoradiographic methods and the
      Patlak method, showed a high correlation. The simulation study showed a 16.8+/
      3.3% increase in the SUV values from 50 to 70 min, but only a 1.3+/-2.8% change
      in the Ki values calculated with the autoradiographic method. CONCLUSION:
      Compared to the SUV, the autoradiographic Ki values are advantageous for various
      reasons. First, they are much less dependent on the time of acquisition than the
      SUV. Second, their calculation does not require the knowledge of the body weight
      or the injected activity. Furthermore, the values are comparable to the ones
      obtained with the widely accepted Patlak method. The method can be easily
      implemented in a clinical setting, as it uses only one static scan.

PMID- 21843780
TI  - Improving the quantitation accuracy in noninvasive small animal single photon
      emission computed tomography imaging.
AB  - INTRODUCTION: Noninvasive imaging of small animals to measure biodistributions
      and pharmacokinetics of radiolabeled agents is increasingly seen as an effective
      alternative to external counting of tissues obtained by sacrifice and dissection.
      However, we have observed important disagreements in measuring the accumulation
      of (111)In-labeled antibodies in organs such as liver and kidneys when comparing
      imaging to ex vivo counting in the same animals. This study was conducted to
      establish whether this discrepancy could be minimized by selecting the region of
      interest (ROI) in images at the appropriate color threshold and by correcting for
      the estimated radioactivity within the blood pool of these organs during imaging.
      METHODS: Vials with known concentrations of (111)In as phantoms were imaged on a
      Bioscan NanoSPECT/CT. Thereafter, an (111)In-DTPA-IgG antibody as the test agent
      was administered intravenously to normal rats, and whole body acquisitions were
      obtained at 2, 24 or 48 h. Immediately following imaging, the animals were
      sacrificed, the tissues were removed for ex vivo counting and the radioactivity
      accumulations were then compared. RESULTS: The phantom measurements showed that
      accuracy depended upon setting the correct ROI and that, in turn, depended upon
      setting the appropriate threshold of the color scale. Under the most unfavorable
      conditions, this error did not exceed 60%. Compared to the results of ex vivo
      counting, quantitation by imaging provided high values in liver and kidneys at
      all three time points by as much as 140%. However, by using the blood
      radioactivity at the time of sacrifice and the known blood volume in these
      organs, the disagreement was reduced in all cases to below 25%. CONCLUSION: In
      this study, the discrepancy in quantitating organ radioactivity accumulations
      between noninvasive imaging and necropsy was primarily due to blood pool
      radioactivity contributing to the in vivo images. The discrepancy may be
      minimized by subtracting an estimate of this contribution.

PMID- 21843781
TI  - Preparation and biological evaluation of (177)Lu conjugated PR81 for
      radioimmunotherapy of breast cancer.
AB  - AIM: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen
      that is over expressed in 80% of breast cancers. In this study, we developed a
      method for indirect labeling of PR81 with lutetium-177 and performed all
      preclinical qualifications in production of a biologic agent for
      radioimmunotherapy of breast cancer. MATERIALS AND METHODS: The radiochemical
      purity and in vitro stability of (177)Lu labeled PR81 was determined by instant
      thin layer chromatography. The immunoreactivity and cell toxicity of the complex
      were tested on MCF7 cell line. The biodistribution and scintigraphy studies were
      performed in BALB/c mice with breast tumor. RESULTS: The radiochemical purity was
      91.2+/-3.8% after 2 h. The in vitro stabilities in phosphate buffer and human
      blood serum were 83.1+/-3.4% and 76.2+/-3.6% at 96 h, respectively. The
      immunoreactivity of the complex was 83.4+/-2.4%. The cell toxicity study showed
      that the complex inhibited 85.2+/-3.4% growth of MCF7 cells at a concentration of
      2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the
      accumulation of the complex at the site of tumors with high sensitivity and
      specificity. CONCLUSION: The results showed that one may consider (177)Lu-DOTA
      PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which
      needs further investigations.

PMID- 21843782
TI  - Preparation and biological evaluation of 3-[(76)Br]bromo-alpha-methyl-L-tyrosine,
      a novel tyrosine analog for positron emission tomography imaging of tumors.
AB  - INTRODUCTION: 3-[(18)F]fluoro-alpha-methyl-l-tyrosine ([(18)F]FAMT) is a useful
      amino acid tracer for positron emission tomography (PET) imaging of malignant
      tumors. FAMT analogs labeled with (76)Br, a positron emitter with a long half
      life (t(1/2)=16.1 h), could potentially be widely used as amino acid tracers for
      tumor imaging. In this study, 3-[(76)Br]bromo-alpha-methyl-l-tyrosine
      ([(76)Br]BAMT) was designed, and its usefulness was evaluated as a novel PET
      tracer for imaging malignant tumors. METHODS: In this study, both [(76)Br]BAMT
      and [(77)Br]BAMT were prepared. The in vitro and in vivo stability of
      [(77)Br]BAMT was evaluated by HPLC analysis. Cellular uptake and retention of
      [(77)Br]BAMT and [(18)F]FAMT were evaluated using LS180 colon adenocarcinoma
      cells. Biodistribution studies were performed in normal mice and in LS180 tumor
      bearing mice, and the tumors were imaged with a small-animal PET scanner.
      RESULTS: [(77)Br]BAMT was stable in vitro but was catabolized after
      administration in mice. Cellular accumulation and retention of [(77)Br]BAMT were
      significantly higher than those of [(18)F]FAMT. In biodistribution studies, the
      tumor accumulation of [(77)Br]BAMT was higher than that of [(18)F]FAMT. However,
      some level of debromination was seen, which caused more retention of
      radioactivity in the blood and organs than was seen with [(18)F]FAMT. PET imaging
      with [(76)Br]BAMT enabled clear visualization of the tumor, and the whole-body
      image using [(76)Br]BAMT was similar to that using [(18)F]FAMT. CONCLUSIONS:
      [(77)Br]BAMT showed high levels of tumor accumulation, and [(76)Br]BAMT enabled
      clear visualization of the tumor by PET imaging. Although an improvement in
      stability is still needed, (76)Br-labeled FAMT analogs could potentially serve as
      PET tracers for the imaging of malignant tumors.

PMID- 21843783
TI  - Characterization of iodinated adrenomedullin derivatives suitable for lung
      nuclear medicine.
AB  - INTRODUCTION: We have recently demonstrated the effectiveness of 99m-technetium
      adrenomedullin (AM) as a new molecular lung imaging agent that could provide
      significant advantages for the diagnosis and follow-up of disorders affecting the
      pulmonary circulation such as pulmonary embolism and pulmonary hypertension.
      Having the possibility to conjugate the targeting molecule with different
      radionuclides would offer more flexibility and potential advantages depending on
      clinical situations. Since various iodine isotopes are currently used in nuclear
      medicine and in pharmacological studies, we have evaluated which iodination
      method should be privileged in order to produce a good iodinated AM-derived
      nuclear medicine agent. METHODS: Synthetic AM was labeled with iodine through
      chemical and lactoperoxidase oxidation methods. Position of the iodine atom on
      the peptide was determined by MALDI-TOF mass spectrometry analysis following
      cyanogen bromide cleavage and carboxypeptidase Y digestion. Binding affinity of
      iodinated AM analogues was evaluated by competition and saturation binding
      experiments on dog lung preparations. RESULTS: In this study, we demonstrated
      that, upon lactoperoxidase oxidation, iodination occurred at Tyr(1) and that this
      radioligand retained higher binding affinity and specificity over preparations
      obtained through chemical oxidation. CONCLUSIONS: These results emphasize the
      fact that even a small chemical modification, i.e. iodination, might deeply
      modify the pharmacological profile of a compound and support observations that
      the C-terminal tail of human AM plays an important role in the AM receptor
      binding process. Consequently, incorporation of a radionuclide to produce an AM
      based nuclear medicine agent should privilege the N-terminus of the molecule.

PMID- 21843784
TI  - Radiosynthesis and in vivo evaluation of [(11)C]MP-10 as a positron emission
      tomography radioligand for phosphodiesterase 10A.
AB  - INTRODUCTION: The aim of this study was to evaluate a newly reported positron
      emission tomography (PET) radioligand [(11)C]MP-10, a potent and selective
      inhibitor of the central phosphodiesterase 10A enzyme (PDE10A) in vivo, using
      PET. METHODS: A procedure was developed for labeling MP-10 with carbon-11.
      [(11)C]MP-10 was evaluated in vivo both in the pig and baboon brain. RESULTS:
      Alkylation of the corresponding desmethyl compound with [(11)C]methyl iodide
      produced [(11)C]MP-10 with good radiochemical yield and specific activity. PET
      studies in the pig showed that [(11)C]MP-10 rapidly entered the brain reaching
      peak tissue concentration at 1-2 min postadministration, followed by washout from
      the tissue. Administration of a selective PDE10A inhibitor reduced the binding in
      all brain regions to the levels of the cerebellum, demonstrating the saturability
      and selectivity of [(11)C]MP-10 binding. In the nonhuman primate, the brain
      tissue kinetics of [(11)C]MP-10 were slower, reaching peak tissue concentrations
      at 30-60 min postadministration. In both species, the observed rank order of
      regional brain signal was striatum>diencephalon>cortical regions=cerebellum,
      consistent with the known distribution and concentration of PDE10A. [(11)C]MP-10
      brain kinetics were well described by a two-tissue compartment model, and
      estimates of total volume of distribution (V(T)) were obtained. Blocking studies
      with unlabeled MP-10 revealed the suitability of the cerebellum as a reference
      tissue and enabled the estimation of regional binding potential (BP(ND)) as the
      outcome measure of specific binding. Quantification of [(11)C]MP-10 binding using
      the simplified reference tissue model with cerebellar input function produced
      BP(ND) estimates consistent with those obtained by the two-tissue compartment
      model. CONCLUSION: We demonstrated that [(11)C]MP-10 possesses good
      characteristics for the in vivo quantification of the PDE10A in the brain by PET.

PMID- 21843785
TI  - Evaluation of (111)In labeled antibodies for SPECT imaging of mesothelin
      expressing tumors.
AB  - INTRODUCTION: Mesothelin is expressed in many cancers, especially in mesothelioma
      and lung, pancreatic and ovarian cancers. In the present study, we evaluate
      (111)In labeled antimesothelin antibodies as an imaging bioprobe for the SPECT
      imaging of mesothelin-expressing tumors. METHODS: We radiolabeled the
      antimesothelin antibodies mAbMB and mAbK1 with (111)In using the p-SCN-bn-DTPA
      chelator. The immunoreactivity, affinity (K(d)) and internalization properties of
      the resulting two (111)In labeled antibodies were evaluated in vitro using
      mesothelin-expressing A431K5 cells. The biodistribution and microSPECT/CT imaging
      studies with (111)In labeled antibodies were performed in mice bearing both
      mesothelin positive (A431K5) and mesothelin negative (A431) tumors. RESULTS: In
      vitro studies demonstrated that (111)In-mAbMB bound with a higher affinity
      (K(d)=3.6+/-1.7 nM) to the mesothelin-expressing A431K5 cells than did the
      (111)In-mAbK1 (K(d)=29.3+/-2.3 nM). (111)In-mAbMB was also internalized at a
      greater rate and extent into the A431K5 cells than was the (111)In-mAbK1.
      Biodistribution studies showed that (111)In-mAbMB was preferentially localized in
      A431K5 tumors when compared to A431 tumors. At the low dose, the peak A431K5
      tumor uptake of 9.65+/-2.65% ID/g (injected dose per gram) occurred at 48 h,
      while at high dose tumor uptake peaked with 14.29+/-6.18% ID/g at 72 h. Non
      specific localization of (111)In-mAbMB was mainly observed in spleen.(111)In
      mAbK1 also showed superior localization in A431K5 tumors than in A431 tumors, but
      the peak uptake was only 3.04+/-0.68% ID/g at 24 h. MicroSPECT/CT studies
      confirmed better visualization of A431K5 tumors with (111)In-mAbMB, than with
      (111)In-mAbK1. CONCLUSION: SPECT imaging of mesothelin expressing tumors was
      demonstrated successfully. Our findings indicate that the antimesothelin antibody
      mAbMB has the potential to be developed into a diagnostic agent for imaging
      mesothelin-expressing cancers.

PMID- 21843787
TI  - Cyclotron production of (99m)Tc: experimental measurement of the
      (100)Mo(p,x)(99)Mo, (99m)Tc and (99g)Tc excitation functions from 8 to 18 MeV.
AB  - INTRODUCTION: The cyclotron-based (100)Mo(p,2n)(99m)Tc transformation has been
      proposed as a viable alternative to the reactor based (235)U(n,f)(99)Mo->(99m)Tc
      strategy for production of (99m)Tc. Despite efforts to theoretically model the
      amount of ground-state (99g)Tc present at end of bombardment for the (p,2n)
      reaction, experimental validation has yet to be performed. The co-production of
      (99g)Tc may have important implications in both the subsequent
      radiopharmaceutical chemistry and patient dosimetry upon injection. METHODS: To
      determine the extent of (99g)Tc co-production, we have experimentally measured
      the (100)Mo(p,x)(99)Mo, (99m)Tc, and (99g)Tc excitation functions in the 8-18 MeV
      range using a combination of natural abundance and 97.42% enriched (100)Mo foils
      along with gamma-ray spectrometry and ICP-MS. Although the excitation functions
      for production of (99)Mo and (99m)Tc have been presented previously in the
      literature, to the best of our knowledge, this work presents the first
      experimental evaluation of the (100)Mo(p,2n)(99g)Tc excitation function. RESULTS:
      From the experimental cross-section measurements, the (99m)Tc production yields
      and (99m)Tc/(99m+g)Tc nuclei ratio were calculated for various thick target
      irradiation conditions. Results suggest that TBq quantities of (99m)Tc can be
      achieved with a (99m)Tc/(99m+g)Tc nuclei ratio that is on par with the current
      (99)Mo/(99m)Tc generator standard eluted at a 24-h frequency. CONCLUSION: These
      findings suggest that the cyclotron production of (99m)Tc may be a feasible
      alternative to the current reactor-based production strategy.

PMID- 21843786
TI  - Striatal adenosine A(2A) receptor-mediated positron emission tomographic imaging
      in 6-hydroxydopamine-lesioned rats using [(18)F]-MRS5425.
AB  - INTRODUCTION: A(2A) receptors are expressed in the basal ganglia, specifically in
      striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain
      region undergoes degeneration of presynaptic dopamine projections and depletion
      of dopamine in Parkinson's disease. We developed an (18)F-labeled A(2A) analog
      radiotracer ([(18)F]-MRS5425) for A(2A) receptor imaging using positron emission
      tomography (PET). We hypothesized that this tracer could image A(2A) receptor
      changes in the rat model for Parkinson's disease, which is created following
      unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into
      the substantia nigra. METHODS: [(18)F]-MRS5425 was injected intravenously in
      anesthetized rats, and PET imaging data were collected. Image-derived percentage
      injected doses per gram (%ID/g) in regions of interest was measured in the
      striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after
      intravenous administration of saline (baseline), D(2) agonist quinpirole (1.0
      mg/kg) or D(2) antagonist raclopride (6.0 mg/kg). RESULTS: Baseline %ID/g reached
      a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly
      thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the
      lesioned side compared to the intact side, and the baseline total %ID/g (data
      from both hemispheres were combined) was significantly higher compared to
      quinpirole stimulation starting from 4.5 min until the end of acquisition at 30
      min. Raclopride did not produce any change in uptake compared to baseline or
      between the hemispheres. CONCLUSION: Thus, increase of A(2A) receptor-mediated
      uptake of radioactive MRS5425 could be a superior molecular target for
      Parkinson's imaging.

PMID- 21843789
TI  - The effects of different ecophysiological factors on ochratoxin A production.
AB  - Mycotoxin biosynthesis is affected by peculiar agro-ecosystem dependent
      conditions. Accordingly, the correlation between mycotoxin contamination and
      environmental condition change scenarios should be carefully considered. This is
      because fungal colonization and mycotoxin contamination could critically impair
      the availability of food products, especially in poor countries. At any time, the
      agricultural products might become susceptible to fungal contamination and
      mycotoxin production in uncontrolled storage. From 2000 to 2010, many studies
      were carried out in the case of the effects of different parameters on ochratoxin
      A (OTA) production by fungi in order to avoid providing the appropriate
      conditions for producing OTA. Water activity (a(w)), temperature, type of species
      and the substrates were introduced as the most important in these articles. This
      paper reviews the major published articles regarding the different
      ecophysiological factors influencing on OTA production.

PMID- 21843788
TI  - The low-energy beta(-) and electron emitter (161)Tb as an alternative to (177)Lu
      for targeted radionuclide therapy.
AB  - INTRODUCTION: The low-energy beta(-) emitter (161)Tb is very similar to (177)Lu
      with respect to half-life, beta energy and chemical properties. However, (161)Tb
      also emits a significant amount of conversion and Auger electrons. Greater
      therapeutic effect can therefore be expected in comparison to (177)Lu. It also
      emits low-energy photons that are useful for gamma camera imaging. METHODS: The
      (160)Gd(n,gamma)(161)Gd->(161)Tb production route was used to produce (161)Tb by
      neutron irradiation of massive (160)Gd targets (up to 40 mg) in nuclear reactors.
      A semiautomated procedure based on cation exchange chromatography was developed
      and applied to isolate no carrier added (n.c.a.) (161)Tb from the bulk of the
      (160)Gd target and from its stable decay product (161)Dy. (161)Tb was used for
      radiolabeling DOTA-Tyr3-octreotate; the radiolabeling profile was compared to the
      commercially available n.c.a. (177)Lu. A (161)Tb Derenzo phantom was imaged using
      a small-animal single-photon emission computed tomography camera. RESULTS: Up to
      15 GBq of (161)Tb was produced by long-term irradiation of Gd targets. Using a
      cation exchange resin, we obtained 80%-90% of the available (161)Tb with high
      specific activity, radionuclide and chemical purity and in quantities sufficient
      for therapeutic applications. The (161)Tb obtained was of the quality required to
      prepare (161)Tb-DOTA-Tyr3-octreotate. CONCLUSIONS: We were able to produce
      (161)Tb in n.c.a. form by irradiating highly enriched (160)Gd targets; it can be
      obtained in the quantity and quality required for the preparation of (161)Tb
      labeled therapeutic agents.

PMID- 21843790
TI  - Appraisal of anti-inflammatory and free radical scavenging activities of ethanol
      extract of Ilex ficoidea Hemsl and Ilex centrochinensis S.Y. Hu.
AB  - This study was to appraise the anti-inflammatory and free radical scavenging
      activities of ethanol extracts of Ilex ficoidea Hemsl (EIFH) and Ilex
      centrochinensis S.Y. Hu (EICC). Anti-inflammatory activities were evaluated using
      xylene-induced ear edema and the cotton pellet granuloma tests. Some antioxidants
      produced during chronic inflammation were quantitated and the DPPH, superoxide
      anion and hydroxyl free radicals scavenging activities in vitro were also
      investigated. EICC showed a significant anti-inflammatory effect during the acute
      inflammation and chronic inflammation without any acute oral toxicity. However,
      EIFH exhibited a negligible anti-acute inflammatory and a moderate anti-chronic
      inflammatory activity. EICC significantly inhibited the formation of MDA and
      markedly raised the activities of SOD, CAT and GSH-Px. EIFH could reduce the
      level of MDA and elevate the activity of SOD only at the high dose. The free
      radical scavenging activities of EICC are higher than that of EIFH. These results
      suggest that EICC possesses significant anti-inflammatory and free radical
      scavenging activities. The anti-inflammatory mechanism is attributed, in part, to
      enhance the activities of antioxidant enzymes.

PMID- 21843791
TI  - Effect of genetic polymorphism of GSTM1 and GSTT1 genotypes on cytogenetic
      biomarkers among coaltar workers.
AB  - Chromosomal aberrations (CAs) in peripheral blood lymphocytes and micronuclei
      (MN) in exfoliated buccal cells have been used for decades as cytogenetic
      biomarkers to investigate genotoxicity among occupationally or environmentally
      exposed population. In our study, we investigated the association of increased
      cytogenetic damage with genetic polymorphism in glutathione-S transferase
      genotypes among occupationally exposed 115 coaltar workers and 105 unexposed
      controls. We found higher mean value of chromosome aberrations (chromatid type
      2.01+/-1.76; chromosomal type-2.22+/-1.73) and buccal micronuclei (BMN-7.10+/
      1.56) in exposed subjects when compared to referents (chromatid type-0.82+/-.51;
      chromosomal type-0.87+/-.54; BMN-5.09+/-2.88). We observed that individuals
      having null genotype of GSTM1 and GSTT1 have significantly higher frequency of
      CAs and MN. Despite of small sample size, our findings suggest a significant
      association between polymorphism of glutathione-S transferase genotypes and
      cytogenetic biomarkers which are considered as early effects of genotoxic
      carcinogens.

PMID- 21843792
TI  - Psidium guajava extract inhibits thymus and activation-regulated chemokine
      (TARC/CCL17) production in human keratinocytes by inducing heme oxygenase-1 and
      blocking NF-kappaB and STAT1 activation.
AB  - Psidium guajava (P. guajava) is a food and medicinal plant with antioxidant, anti
      inflammatory, and anti-allergic activities that support its traditional uses. The
      aim of this study was to determine the effects of P. guajava ethyl acetate
      extract (PGEA) on atopic dermatitis and to investigate the possible mechanisms by
      which PGEA inhibits cytokine-induced Th2 chemokine expression in HaCaT human
      keratinocyte cells. We found that PGEA suppressed the IFN-gamma/TNF-alpha-co
      induced production of thymus and activation-regulated chemokine (TARC) protein
      and mRNA in HaCaT cells. Additionally, PGEA inhibited the TNF-alpha/IFN-gamma-co
      induced activation of NF-kappaB and STAT1 and increased the expression of heme
      oxygenase-1 (HO-1) protein and mRNA. HO-1 inhibitor enhanced the suppressive
      effects of PGEA on TNF-alpha/IFN-gamma-co-induced TARC production and gene
      expression. Collectively, these data demonstrate that PGEA inhibits chemokine
      expression in keratinocytes by inducing HO-1 expression and it suggests a
      possible therapeutic application in atopic dermatitis and other inflammatory skin
      diseases.

PMID- 21843793
TI  - Protective role of Centella asiatica on lead-induced oxidative stress and
      suppressed reproductive health in male rats.
AB  - Centella asiatica has been mentioned in ancient ayurvedic text of the Indian
      system of medicine for its properties to promote intelligence. The objective of
      the present study was to investigate the beneficial effects of C. asiatica on
      lead-induced oxidative stress and suppressed reproductive performance in male
      rats. Significant decrease in the weights of testes and epididymis were observed
      in lead treated animals. Exposure to lead acetate significantly increased
      malondialdehyde levels with a significant decrease in the superoxide dismutase
      and catalase activities in the liver, brain, kidneys and testes of rats.
      Epididymal sperm count, viable sperms, motile sperms and HOS-tail coiled sperms
      decreased significantly in lead-exposed rats. Testicular steroidogenic enzyme
      activities also decreased significantly in lead-exposed rats. No significant
      changes in the selected reproductive variables were observed in the plant extract
      alone treated rats. Whereas, co-administration of aqueous extracts of C. asiatica
      to lead exposed rats showed a significant increase in the weights of reproductive
      organs, reduction in lead-induced oxidative stress in the tissues and improvement
      in selected reproductive parameters over lead-exposed rats indicating the
      beneficial role of C. asiatica to counteract lead-induced oxidative stress and to
      restore the suppressed reproduction in male rats.

PMID- 21843794
TI  - Association of methamidophos and sleep loss on reproductive toxicity of male
      mice.
AB  - This study investigated the effects of organophosphate exposure on the male
      reproductive system of mice submitted to chronic sleep loss condition. Adult
      Swiss mice were distributed into 4 groups: control; methamidophos (MTP); sleep
      restriction (SR); and MTP+SR. The dose of methamidophos was 0.002 mgkg(-1)day(-1)
      (half of the Acceptable Daily Intake). Sleep restriction condition was 21 h day(
      1) during 15 days. In relation to control group, MTP treatment induced a
      significant reduction of 12% on morphologically normal spermatozoa in both MTP
      and MTP+SR groups. In addition, the absolute and relative weights of the seminal
      vesicles were decreased (MTP, -34%; MTP+SR, -45%). Epididymal fat was reduced in
      SR groups (SR, -64%; MTP+SR, -58%). Plasma testosterone levels were significantly
      decreased in MTP and SR groups, and progesterone levels were increased 8 times in
      MTP+SR in comparison with the control group. The corticosterone levels were
      unaffected by MTP or SR conditions. Thus, low dose MTP exposure resulted in
      deleterious effects on the male reproductive system. Sleep loss associated with
      MTP potentiated the effect on steroidogenesis, mainly in terms of progesterone
      levels.

PMID- 21843795
TI  - Evaluation of four Cameroonian medicinal plants for anticancer, antigonorrheal
      and antireverse transcriptase activities.
AB  - Methanol extracts from the leaves, bark and roots of four Cameroonian medicinal
      plants, Bersama engleriana, Cupressus lusitanica, Vitellaria paradoxa and
      Guibourtia tessmannii were tested for their in vitro cytotoxicity, antigonorrheal
      and antireverse transcriptase activities. The XTT (2,3-bis[2-methoxy-4-nitro-5
      sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay, the dilution
      method and reverse transcriptase (RT) assay were used for the investigations.
      Preliminary phytochemical analysis of the extracts was also conducted using
      standard methods. Results showed that all extracts contained compounds belonging
      to the classes of phenols and terpenoids. They were also able to reduce in dose
      dependent manner, the proliferation of the cancer THP-1, DU145, HeLa, MCF-7,
      HepG2 and the normal Vero cells. IC(50) values below 30MUg/ml were noted with
      extract from the three parts of B. engleriana on at least two of the five studied
      cancer cell lines, the lowest value of 5.9MUg/ml being obtained with sample from
      the bark. IC(50) values below 30MUg/ml were also recorded with extracts from the
      leaves (on HeLa cells) and bark (on MCF-7) of G. tessmanii, and that from the
      bark of C. lusitanica on MCF-7. Extracts from B. engleriana and those from the
      bark of V. paradoxa gave the minimal inhibitory concentrations (MIC) values below
      100MUg/ml on most of the 10 tested Nesseria gonorrhoeae strains. Extracts from B.
      engleriana also inhibited more than 80% the activity of the Human Immuno
      deficiency Virus (HIV) enzyme. Finally, the results of the present study provide
      baseline information for the use of B. engleriana, C. lusitanica, G. tessmanii,
      V. paradoxa.

PMID- 21843796
TI  - The protective effect of C-phycocyanin on paraquat-induced acute lung injury in
      rats.
AB  - To investigate the potential protective effect of C-phycocyanin (PC) on paraquat
      (PQ)-induced acute lung injury, rats were divided into control, PQ-treated and
      PQ+PC-treated groups. Rats in PQ-treated group were orally administered with
      50mg/kg PQ, and rats in PQ+PC-treated group were intraperitoneally injected with
      50mg/kg PC after administration of PQ. At 8, 24, 48 and 72h after treatments, GSH
      Px and SOD activities, MDA levels in plasma and BALF, HYP, NF-kappaB, IkappaB
      alpha and TNF-alpha contents in lung tissues were measured. The pathological
      changes in lung were observed. After treatment with PC, the levels of MDA and the
      relative contents of NF-kappaB and TNF-alpha were significantly decreased, the
      activities of GSH-Px and SOD and the relative contents of IkappaB-alpha were
      significantly increased. The degree of rat lung damage was obviously reduced in
      PQ+PC-treated group. The results suggested that PC treatment significantly
      attenuated PQ-induced acute lung injury.

PMID- 21843797
TI  - Association of oxidative stress with the formation of reproductive toxicity from
      mercury exposure on hermaphrodite nematode Caenorhabditis elegans.
AB  - Here we selected HgCl(2) to investigate the mechanism of Hg toxicity on
      reproduction in hermaphrodite nematodes. Accompanied with decrease of brood size,
      Hg exposure caused severe deficits in egg number in uterus, egg laying and
      reproductive structures, including gonad arms and vulva, and formation of
      protruding phenotype for vulva. Meanwhile, Hg exposure induced severe stress
      response and oxidative damage in gonad and vulva. Pre-treatment with vitamin E, a
      potent antioxidant, at the L2-larval stage prevented the oxidative damage and
      formation of reproductive deficits in Hg exposed nematodes; however, pre
      treatment with paraquat, a regent generating superoxide anions, induced more
      severe reproductive deficits in Hg exposed nematodes. Moreover, Hg exposure
      increased expression of clk-2 and isp-1 genes, whose mutations decrease ROS
      production, and decreased expression of mev-1 and gas-1 genes, whose mutations
      increase ROS production. Thus, oxidative stress may be essential for the
      induction of reproductive deficits in Hg exposed hermaphrodite nematodes.

PMID- 21843798
TI  - XRCC1 gene variants and possible links with chromosome aberrations and
      micronucleus in active and passive smokers.
AB  - Tobacco addiction is a major risk for diseases such as cancers, heart attack,
      etc. Tobacco smoke constitutes environmental toxins that are the major
      preventable leading cause of death worldwide. We investigated the influence of
      tobacco smoke on cytogenetic parameters (chromosomal aberrations and micronuclei)
      and the influence of XRCC1 arg399gln polymorphism on the cytogenetic parameters
      of the exposed subjects. The cases for this study include active and passive
      smokers. They were divided into three groups in accordance with duration of
      exposure to tobacco smoke. We observed changes in the frequency of chromosomal
      aberrations and micronuclei among the exposed subjects and controls. Of the three
      groups of exposed subjects, group III of active smokers and group III of passive
      smokers showed higher number of chromosomal aberrations and micronuclei when
      compared to controls, group I and group II of active and passive smokers. The
      XRCC1 arg399gln polymorphic variant gln/gln, influenced the extent of genotoxic
      damage in chromosomes and frequency of in micronuclei the three variants
      (arg/arg, arg/gln and gln/gln), gln/gln harbored significantly (P<0.05) higher
      number of aberrations than the arg/arg and arg/gln. In this context, the results
      observed in our study indicated that the single nucleotide polymorphism on
      XRCC1codon 399 influenced the frequencies of chromosomal aberrations and
      micronuclei.

PMID- 21843799
TI  - Effect of mangrove black tea extract from Ceriops decandra (Griff.) on hematology
      and biochemical changes in dimethyl benz[a]anthracene-induced hamster buccal
      pouch carcinogenesis.
AB  - Effect of the black tea extracted from a mangrove plant species, Ceriops decandra
      (Griff.) was studied on dimethyl benz[a]anthracene (DMBA)-induced changes in
      blood hematology and plasma non-enzymatic antioxidants in male hamsters. Hamsters
      were painted with 0.5% solution of DMBA in liquid paraffin on the right buccal
      pouch three times in a week up to 14 weeks. Each application treated with 0.4mg
      of DMBA. The mangrove black tea extract (MBTE) was administrated orally with
      5mgkg(-1) twice a day and then with DMBA on alternate days. Results showed that
      the DMBA caused a significant (P<0.05) decline in the levels of reduced
      glutathione (GSH), vitamin-C, -E, red blood cells, hemoglobin, mean corpuscular
      volume and hematocrit; and increase in the levels of WBC, platelets, lymphocytes
      and neutrophils. The MBTE prevented the DMBA-induced adverse changes
      significantly in blood and biochemical parameters of the male hamsters. This work
      concluded that the black tea extracted from the coastal mangrove species C.
      decandra prevented the DMBA-induced buccal pouch carcinogenesis in hamsters.

PMID- 21843800
TI  - Bee venom induced cytogenetic damage and decreased cell viability in human white
      blood cells after treatment in vitro: a multi-biomarker approach.
AB  - The aim of this study was to evaluate cytogenotoxic effects of bee venom to human
      lymphocytes and take a look into the mechanisms behind them. Bee venom was tested
      in concentrations ranging from 0.1MUg/ml to 20MUg/ml over different lengths of
      time. Cell viability, type of the cell death, and morphological alterations were
      evaluated using phase-contrast and fluorescent microscopy in addition to DNA
      diffusion assay, whereas cytogenotoxic effects were assessed with the
      micronucleus test. DNA damage and its relation to oxidative stress were evaluated
      combining the standard alkaline and the Fpg-modified comet assay. Our results
      showed lower cell viability, morphological cell alterations, cytogenotoxicity,
      and dominantly necrotic type of cell death in human lymphocytes after treatment
      with bee venom. All the effects were time- and dose-dependent. These results
      provide an insight into the effects of bee venom on the cell structure that could
      be relevant for therapeutic purposes.

PMID- 21843801
TI  - The toxicity potential of pharmaceuticals found in the Douro River estuary
      (Portugal)--experimental assessment using a zebrafish embryo test.
AB  - Fish embryos are a particularly vulnerable stage of development, so they
      represent optimal targets for screening toxicological effects of waterborne
      xenobiotics. Herein, the toxicity potential of two mixtures of pharmaceuticals
      was evaluated using a zebrafish embryo test. One of the mixtures corresponds to
      an environmentally realistic scenario and both have carbamazepine, fenofibric
      acid, propranolol, trimethoprim and sulfamethoxazole. The results evidenced
      morphological alterations, such as spinal deformities and yolk-sac oedemas.
      Moreover, heart rates decreased after both mixture exposures, e.g., at 48hpf,
      highest mixture versus blank control (47.8+/-4.9 and 55.8+/-3.7 beats/30s,
      respectively). The tail lengths also diminished significantly from 3208+/-145MUm
      in blank control to 3130+/-126MUm in highest mixture. The toxicological effects
      were concentration dependent. Mortality, hatching rate and the number of
      spontaneous movements were not affected. However, the low levels of
      pharmaceuticals did interfere with the normal development of zebrafish, which
      indicates risks for wild organisms.

PMID- 21843802
TI  - Benzo(a)pyrene-induced metabolic responses in Manila clam Ruditapes philippinarum
      by proton nuclear magnetic resonance ((1)H NMR) based metabolomics.
AB  - Benzo(a)pyrene is an important polycyclic aromatic hydrocarbon (PAH) which causes
      carcinogenic, teratogenic and mutagenic effects in various species and the level
      of contamination of this toxic agent in the marine environment is of great
      concern. In this study, metabolic responses induced by two doses (0.02 and
      0.2MUM) of BaP were characterized in the gill tissues of Manila clam Ruditapes
      philippinarum after exposure for 24, 48 and 96h. The high dose (0.2MUM) of BaP
      induced the disturbances in energy metabolism and osmotic regulation based on the
      metabolic biomarkers such as succinate, alanine, glucose, glycogen, branched
      chain amino acids, betaine, taurine, homarine, and dimethylamine in clam gills
      after 24h of exposure. In addition, hormesis induced by BaP was found in clams
      exposed to both doses of BaP. Overall, our results demonstrated the applicability
      of metabolomics for the elucidation of toxicological effects of marine
      environmental contaminants in a selected bioindicator species such as the Manila
      clam.

PMID- 21843803
TI  - Molluscicidal activity of cardiac glycosides from Nerium indicum against Pomacea
      canaliculata and its implications for the mechanisms of toxicity.
AB  - Cardiac glycosides from fresh leaves of Nerium indicum were evaluated for its
      molluscicidal activity against Pomacea canaliculata (golden apple snail: GAS)
      under laboratory conditions. The results showed that LC(50) value of cardiac
      glycosides against GAS was time dependent and the LC(50) value at 96 h was as low
      as 3.71 mg/L, which was comparable with that of metaldehyde at 72 h (3.88 mg/L).
      These results indicate that cardiac glycosides could be an effective molluscicide
      against GAS. The toxicological mechanism of cardiac glucosides on GAS was also
      evaluated through changes of selected biochemical parameters, including
      cholinesterase (ChE) and esterase (EST) activities, glycogen and protein contents
      in hepatopancreas tissues of GAS. Exposure to sublethal concentrations of cardiac
      glycosides, GAS showed lower activities of EST isozyme in the later stages of the
      exposure period as well as drastically decreased glycogen content, although total
      protein content was not affected at the end of 24 and 48 h followed by a
      significant depletion at the end of 72 and 96 h. The initial increase followed by
      a decline of ChE activity was also observed during the experiment. These results
      suggest that cardiac glycosides seriously impair normal physiological metabolism,
      resulting in fatal alterations in major biochemical constituents of
      hepatopancreas tissues of P. canaliculata.

PMID- 21843804
TI  - Close association of intestinal autofluorescence with the formation of severe
      oxidative damage in intestine of nematodes chronically exposed to Al(2)O(3)
      nanoparticle.
AB  - In nematodes, acute exposure (24-h) to 8.1-30.6 mg/L Al(2)O(3)-nanoparticles
      (NPs) or Al(2)O(3) did not influence intestinal autofluorescence, whereas chronic
      exposure (10-d) to Al(2)O(3)-NPs at concentrations of 8.1-30.6 mg/L or Al(2)O(3)
      at concentrations of 23.1-30.6 mg/L induced significant increases of intestinal
      lipofuscin accumulation, and formation of severe stress response and oxidative
      damage in intestines. Moreover, significant differences of intestinal
      autofluorescence, stress response and oxidative damage in intestines of Al(2)O(3)
      NPs exposed nematodes from those in Al(2)O(3) exposed nematodes were detected at
      examined concentrations. Oxidative damage in intestine was significantly
      correlated with intestinal autofluorescence in exposed nematodes, and oxidative
      damage in intestine was more closely associated with intestinal autofluorescence
      in nematodes exposed to Al(2)O(3)-NPs than exposed to Al(2)O(3). Thus, chronic
      exposure to Al(2)O(3)-NPs may cause adverse effects on intestinal lipofuscin
      accumulation by inducing the formation of more severe oxidative stress in
      intestines than exposure to Al(2)O(3) in nematodes.

PMID- 21843805
TI  - Rapid detection of ciprofloxacin effects on Fusarium graminearum and F. avenaceum
      cells in modulating environmental pH using a reactive, non-toxic food-dye
      indicator.
AB  - The objective of the study was to assess the effect of ciprofloxacin antibiotic
      on the physiological or phenotypic characteristics of food-borne toxigenic
      Fusarium graminearum and F. avenaceum molds under in vitro conditions. In the
      presence of ciprofloxacin, Fusarium mycelia growth and morphology were altered
      based on the antibiotic concentration range used. Results showed that
      ciprofloxacin in concentrations >=40MUg/mL induced chlamydospore formation in
      Fusaria and as such, this antibiotic should be considered as an important abiotic
      stress factor and growth inhibitor. A novel method was investigated to correlate
      chlamydospore formation with the colour changes observed in FD&C Green Number 3,
      a common water soluble food dye. The antibiotic-treated F. graminearum and F.
      avenaceum isolates produced chamydospores, which in turn altered environmental pH
      with concomitant changes in the colour and intensity of the dye. The colour
      changes observed as a function of environmental pH were supported by instrumental
      methods (pH meter and spectroscopy), and a commercial pH indicator (thymol blue)
      results. In conclusion, we propose that FD&C Green Number 3 can be used as an
      accurate indicator for the rapid assessment of Fusarium molds when grown on
      ciprofloxacin antibiotic-containing substrate. Special emphasis should be given
      to an indirect risk assessment of antibiotic effects on toxic molds.

PMID- 21843806
TI  - Occupational exposure characterization in professional sprayers: clinical utility
      of oxidative stress biomarkers.
AB  - The impact of involuntary exposure to pesticides was studied in a group of
      professional sprayers (S) (25+/-5 years old) exposed to various agrochemicals for
      about 10 years. The results were compared with a group of non exposed people (C).
      S group showed hematological, renal, pancreatic and hepatic biomarkers within the
      reference values established for the general population, including cholinesterase
      activity. In spite of that, all the biochemical tests were statistically
      different compared to C. On the other hand, oxidative stress biomarkers (OSB)
      such as plasma tocopherol and the total reducing ability of plasma were
      significantly decreased, while protein carbonyls, thiobarbituric acid-reactive
      substances, total glutathione and the sum of nitrites and nitrates were increased
      in the exposed group. Results demonstrated that screening laboratory tests could
      not be fully sensitive in detecting sub-clinical exposure to pesticides, and also
      suggest that OSB could be validated and included in health surveillance
      protocols.

PMID- 21843807
TI  - Hydrophobicity-dependent QSARs to predict the toxicity of perfluorinated
      carboxylic acids and their mixtures.
AB  - Perfluorinated carboxylic acids (PFCAs) have wide industrial applications because
      of their unique physicochemical characteristics. However, data on the toxicity of
      much of this chemical class is lacking, particularly with regard to mixture
      toxicity. In this study, the toxicity of individual PFCAs and their mixtures to
      Photobacterium phosphoreum were observed. There was a tendency of increasing
      toxicity from C3 to C14 PFCA and a tendency of decreasing toxicity from C14 to
      C18 PFCA because of "the maximum tolerance of the cell membrane". Using the
      equivalent logK(OW) (octanol-water partition coefficient) and logK(SD) (C(18)
      EmporeTM disks/water partition coefficient), two linear quantitative structure
      activity relationship (QSAR) models were formulated. This indicated both K(SD)
      and K(OW) can describe the hydrophobicity of a single chemical. However, for the
      PFCA mixtures, K(MD) is the more reasonable parameter than K(owmix) to describe
      the hydrophobicity because only the equivalent logK(MD) could be used to predict
      the mixture toxicity.

PMID- 21843808
TI  - The chemopreventive effects of aged garlic extract against cadmium-induced
      toxicity.
AB  - Garlic has been reported in many previous studies as a potent chemopreventive
      agent. The protective effect of garlic has been ascribed to the presence of
      organosulphur compounds (OSC). In this study, the efficacy of aged garlic extract
      (AGE) compared to diallyl disulfide (DADS) in protecting against toxicity induced
      by cadmium (Cd) in 1321N1 and HEK293 cells was investigated. The involvement of
      the transcription factor Nrf2 in this protection was also examined. The results
      show that AGE significantly prevented loss of cell viability in Cd-treated 1321N1
      and HEK293 cells. In comparison DADS had no significant effect in protecting
      HEK293 cells but did protect 1321N1 cells. AGE significantly reduced Cd-induced
      TBARS production and LDH leakage in the two cell lines, and AGE and DADS both
      increased GSH levels in Cd-treated cell lines. Pre-treatment of cells with AGE or
      DADS increased expression of the protective enzyme NAD(P)H:quinone oxidoreductase
      (NQO1), and this was associated with the accumulation of the transcription factor
      Nrf2. These results show that AGE and DADS have beneficial effects against Cd
      induced toxicity, and this protection appears to be mediated via induction of
      cytoprotective enzymes in an Nrf2-dependent manner. This indicates the potential
      for using AGE as a chemoprevention strategy for Cd toxicity.

PMID- 21843809
TI  - Effects of cadmium on proliferation and self-renewal activity of prostate
      stem/progenitor cells.
AB  - Cadmium (Cd) is an occupational and environmental pollutant that induces numerous
      pathological effects, including injuries to prostate. The aim of the present
      study was to investigate the effects of Cd on self-renewal and proliferation of
      prostate stem/progenitor cells (PSPC) and its possible mechanisms. Prostate
      epithelial cells were prepared from mice to form sphere in Matrigel/PrEGM
      supplemented with cadmium chloride (CdCl(2)). The data showed that CdCl(2)
      inhibits sphere-forming ability and proliferation of PSPC in a concentration
      dependent manner. Primary spheres were then passaged to form daughter spheres and
      we found that CdCl(2) suppressed PSPC self-renewal activity, which recovered
      after further passaging. We also detected the protein level of androgen receptor
      (AR) in the spheres of each passage. The results showed that AR in primary
      spheres is suppressed by CdCl(2) in a concentration dependent manner. However, no
      obvious change of AR was found in subsequent passages. The in vivo toxicity of
      CdCl(2) on PSPC was detected by giving mice drinking water with CdCl(2). Our
      results demonstrated in vivo inhibition effect of CdCl(2) on self-renewal
      activity of PSPC. Consistent with in vitro results, self-renewal activity of PSPC
      was recovered after CdCl(2) withdrawal. In addition, CdCl(2) also in vivo
      suppressed PSPC proliferation as indicated by Ki67 immunostaining. Our finding
      suggested that Cd may inhibit proliferation and self-renewal activity of PSPC by
      suppressing AR, which could be important to further understanding the complex
      mechanism of Cd toxicity in prostate.

PMID- 21843810
TI  - Differential gene expression profiles of human leukemia cell lines exposed to
      benzene and its metabolites.
AB  - Benzene is a well-known environmental pollutant that can induce hematotoxicity,
      aplastic anemia, acute myelogenous leukemia, and lymphoma. Benzene toxicity is
      likely mediated through metabolites induced by means of multiple pathways.
      Although benzene metabolites are known to induce oxidative stress and disrupt the
      cell cycle, the mechanism underlying leukemogenesis is not fully understood. The
      aim of this study was to analyze the genome-wide expression profiles of human
      promyelocytic leukemia HL-60 cells that had been exposed to benzene and its
      metabolites. This was carried out using whole human genome oligonucleotide
      microarrays to ascertain potential biomarkers. Genes that were differentially
      expressed (>1.5-fold and p-values <0.05) after exposure to benzene (BZ),
      hydroquinone (HQ), and 1,4-benzoquinone (BQ) were then classified with GO, KEGG
      and GSEA pathway annotation. All genes that were identified were then
      functionally categorized as being involved in the cell cycle, the p53 signaling
      pathway, apoptosis, the MAPK signaling pathway, or the T cell receptor signaling
      pathway. Functionally important genes were further validated by means of real
      time RT-PCR. The results showed that EGR1, PMAIP1, AR, CCL2, CD69, HSPA8,
      SLC7A11, HERPUD1, ELK1, and MKI57 genes altered their expression profiles.
      Similar expression profiles were also found in human erythromyeloblastoid
      leukemia K562 cells and in human leukemic monocyte lymphoma U937 cells. In
      conclusion, gene expression profiles along with GO, KEGG and GSEA pathway
      annotation analysis have provided an insight into the leukemogenesis as well as
      highlighted potential gene-based biomarkers of human leukemia cell lines when
      they are exposed to benzene and its metabolites.

PMID- 21843811
TI  - Antioxidant and antigenotoxic effects of rosemary (Rosmarinus officinalis L.)
      extracts in Salmonella typhimurium TA98 and HepG2 cells.
AB  - In the present study the chemopreventive effects of water soluble AquaROX((r)) 15
      and oil soluble VivOX((r)) 40 rosemary extracts against 4-nitroquinoline-N-oxide
      (NQNO) and 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline (IQ) induced mutagenicity
      in the reverse mutation assays with Salmonella typhimurium TA98 and against t
      butyl hydroperoxide (t-BOOH), benzo(a)pyrene (BaP) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) induced DNA damage in HepG2 cells were
      studied, applying the comet assay. The results showed comparable protective
      effect of AquaROX and VivOX against oxidative DNA damage, whereas protection
      against indirect active genotoxic carcinogens was more efficient by VivOX.

PMID- 21843812
TI  - The effect of alendronate sodium on human erythrocytes.
AB  - Alendronate sodium is a medicine, which is commonly used in osteoporosis
      treatment. Nowadays, this substance is given to patients in tablets, but in
      future it is planned that it will be administrated into human organisms as
      intravenous infusions; therefore, significant interactions of this medicine with
      erythrocytes will be inevitable. It is the reason why we decided to investigate
      the interaction of alendronate sodium with human erythrocytes. The effect of this
      medicine on acetylcholinesterase activity, lipid and protein peroxidation, as
      well as cellular thiol content was examined. Moreover, the effect of alendronate
      sodium on alterations in erythrocytes morphology was assessed. Human erythrocytes
      were incubated with alendronate sodium in the concentrations ranging from 0.33 to
      100 MUM for 1 h and 24 h. No changes have been observed in the parameters
      examined after 1h of incubation of the erythrocytes with this medicine excluding
      the carbonyl groups level. Moreover, no alterations in the activity of
      acetylcholinesterase, the level of thiols as well as in morphology of the
      erythrocytes incubated with alendronate sodium for 24h have been observed. It was
      also proven that alendronate sodium increased the level of reactive oxygen
      species (ROS) but only after 24h of incubation. We have not observed any severe
      changes in cells studied even at the highest dose of bisphosphonates examined,
      thus their usage should not be dangerous for the erythrocytes of people treated
      with these medicines.

PMID- 21843813
TI  - In utero exposure to air pollution lowers erythrocyte antioxidant defense and
      decreases weight in adult mice.
AB  - In this study, we tested the influence of ambient air pollution on different
      phases of development of adult mice. With respect to adult weight, the animals
      that had spent their in utero period exposed to pollution showed less weight gain
      over their lifetime, as well as lower activity levels of the antioxidant enzymes
      catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). Our study
      suggests that contact with atmospheric pollutants during the foetal period
      produces important changes on enzymatic erythrocyte antioxidant defense and
      weight in adult mice.

PMID- 21843814
TI  - Serum unconjugated bisphenol A concentrations in men may influence embryo quality
      indicators during in vitro fertilization.
AB  - Here we assess bisphenol A (BPA) in couples undergoing in vitro fertilization
      (IVF) and indicators of embryo quality; embryo cell number (ECN) and embryo
      fragmentation score (EFS). Twenty-seven couples provided serum on the day of
      oocyte retrieval. Unconjugated BPA was measured by HPLC with Coularray detection.
      Odds ratios (OR) were generated using ordinal logistic regression including
      female and male BPA concentrations, age and race, and day of embryo transfer for
      ECN. Inverse associations are suggested for male BPA with ECN (OR=0.70, P=0.069),
      and EFS (OR=0.54, P=0.009), but not for women. Male BPA exposure may affect
      embryo quality during IVF.

PMID- 21843815
TI  - Is less clinical research being published by surgeons in the United Kingdom?
AB  - INTRODUCTION: Concerns about the decline of surgical research have been expressed
      in parallel to the debate on the future of academic surgery in the United
      Kingdom. The aim of this study was to survey the output of UK surgeons in ten
      high impact general surgical journals between 1987 and 2009 to estimate whether
      less clinical academic activity is occurring. METHODS: Ten general surgical
      journals with consistently the highest impact factors (1.2-7.9) were selected for
      review. All articles excepting letters and news articles were included in the
      study. The region of origin was identified for each paper and classified as USA,
      Japan, Europe, UK and Rest of the World (RoW). In articles from multiple centres,
      the region of the corresponding author was used. RESULTS: Over the study period,
      the annual number of surgical papers published from the UK dropped both in
      absolute values (from 286 to 214) and as a percentage of global output (17.7
      8.8%). The USA also saw a drop (from 867 to 763/yr), while the output has
      increased steadily for Europe (from 266 to 822/yr) and RoW (from 151 to 476/yr).
      In 2009, the percentage of total yearly output was roughly equal for Europe and
      USA (31-33%), UK and Japan (7-8%). CONCLUSIONS: These data suggests that clinical
      surgical research in the UK has suffered over the last 20 years. The declining
      emphasis on research as part of surgical training, the strategic decisions about
      fund allocation, and the increasing role of centres from Europe and RoW may all
      play a role. This limited "snapshot" fails to provide information on the output
      in journals focused on basic science. As more of the current research involves
      collaborations between clinicians and non-clinicians it is likely that many more
      papers were published in such journals during the period analysed. It remains to
      be monitored whether recent initiatives will strengthen academic surgery in the
      UK in future years.

PMID- 21843816
TI  - Audit of trauma case load suitable for a day surgery trauma list and cost
      analysis.
AB  - BACKGROUND: Day surgery trauma lists are becoming an increasingly popular and
      widespread approach to address the inpatient trauma demand on NHS services. A
      'Rapid Access' list initiative was set-up to book patients from an emergency
      pathway who require surgery and also fulfilled the standard day case patient
      criteria but for whom it was safe to wait for over 24 h before going to theatre.
      MATERIALS & METHODS: We performed a prospective audit of the cases undertaken on
      the day surgery trauma list over a 12-month period and analysed the number of
      cases, spectrum of procedures, complications and the cost benefits. RESULTS: A
      total of 119 day surgery trauma cases were performed (42 lists; average of 3
      cases per list; upper limb procedures accounted for 60%.). The overall cost
      benefit for day surgery was calculated as the difference between the tariff and
      the costs for day surgery and inpatient procedures. A cost benefit of L617 per
      case for day surgery over inpatient surgery was noted with a total saving of
      L67,450 for the performed procedures. DISCUSSION: We demonstrate day trauma
      surgery to be a safe and cost effective method of optimising the management of
      the appropriate trauma case workload. Further it reduces demand for inpatient
      beds, provides significant cost savings for the trust and improves patient
      satisfaction.

PMID- 21843817
TI  - Wound infection after reconstructive arterial surgery of the lower limbs: risk
      factors and consequences.
AB  - OBJECTIVE: To identify predictors, and clinical consequences, of postoperative
      wound infection after peripheral vascular surgery. MATERIALS AND METHODS:
      Retrospective cohort study. Potential predictors of wound infection were sought
      among patient related factors and procedure related factors. Patient outcome was
      then analysed according to the incidence of wound infection. RESULTS: Following
      209 procedures, 20 (9.6%) patients suffered a wound infection. On univariate
      analysis, infrainguinal surgery, use of vein graft, and tissue loss were
      associated with wound infection. On multivariate regression, however, only the
      association with use of a vein graft remained (OR = 4.2; 95%CI = 1.2-14.1; P =
      .022): the incidence of wound infection was 16/96 (17%; 95%CI = 9.2-24.1) when a
      vein graft was used and 4/113 (3.5%; 95%CI = .1-7%) when a prosthetic or no graft
      was used. Wound infection was associated with increased mortality (4/20 versus
      9/189; P = .025) but not limb loss (2/20 versus 7/189; P = .208). Median (IQR)
      postoperative hospital stay in patients with wound infection was 22 (15-45) days
      and 8 (5-15) days in those without wound infection (P = .001). CONCLUSIONS: In
      lower limb arterial surgery, wound infection is associated with the use of vein
      grafts, and results in delayed recovery and increased mortality. Measures to
      reduce wound infection should be focussed on such patients.

PMID- 21843818
TI  - Fasciotomy: a call for proper placement.
AB  - INTRODUCTION: It is important that acute compartment syndrome is recognised and
      treated early. Treatment involves surgical decompression and it is imperative
      that this is performed in a timely and appropriate manner. The knowledge of
      plastic and orthopaedic surgery trainees of the safe technique for performing
      lower leg fasciotomy was examined. METHODS: Survey of knowledge of fasciotomy was
      performed amongst plastic and orthopaedic surgery trainees. They were asked to
      fill in a questionnaire during a regional teaching session. RESULTS: There were
      29 respondents; 19 plastic surgery trainees and 10 from orthopaedic surgery. Most
      trainees had little experience of watching, assisting or performing fasciotomies.
      When asked to mark the placement of fasciotomy incisions and plane of dissection,
      only 47% of plastic and 10% of orthopaedic surgery trainees were correct.
      DISCUSSION: Clinical experience and knowledge of lower leg fasciotomy is poor
      amongst trainees surveyed. In this paper, the pathophysiology, diagnosis and
      treatment of compartment syndrome are described. Examples of poorly placed
      fasciotomy incisions, as well as the consequences of these, are also presented.

PMID- 21843819
TI  - Gynaecomastia: a decade of experience.
AB  - BACKGROUND: Gynaecomastia is the most common benign condition of the male breast
      and accounts for up to 80% of male breast referrals. We sought to identify any
      changes in the number of patients referred with the condition and assess its
      impact on clinical practice. METHODS: Patients were identified from two
      prospectively maintained databases. Diagnosis of gynaecomastia was based on
      clinical findings, ultrasound scan (USS) assessment and/or histology. RESULTS:
      There was a significant increase in the number of men referred to a specialist
      unit and diagnosed with gynaecomastia. Gynaecomastia was more prevalent in the
      under twenties age group. Core biopsy (CB) became the histological investigation
      of choice for men with unilateral disease and there was no change in the
      percentage of men undergoing surgery. CONCLUSION: Most men are looking for
      reassurance that their condition is benign and that no intervention is required.
      Thus it is important to offer these men psychological support as part of their
      treatment.

PMID- 21843820
TI  - Enhanced recovery in major colorectal surgery: safety and efficacy in an
      unselected surgical population at a UK district general hospital.
AB  - BACKGROUND: Enhanced Recovery Programmes (ERPs) have been shown to benefit
      recovery following major surgery in selected centres and patient groups, but
      their wider applicability requires continued evaluation. The aims of this study
      were to assess the outcomes of the first 400 consecutive, non-selected patients,
      undergoing major elective colorectal surgery within an Enhanced Recovery
      programme at a UK District General hospital and to examine the effects of patient
      risk factors and operative approach on outcomes. METHODS: Since September 2005
      all patients undergoing major elective colon and rectal surgery at our hospital
      have been treated within an ERP and their data recorded prospectively on a
      database. Safety and efficacy outcomes for the first 400 patients were compared
      using SPSS v14.0 with both a retrospective, pre-ERP group; and according to
      patient risk factors and operative approaches. RESULTS: Median length of stays
      (LOS) reduced from 9 days (IQR 7-11) to 6 days (IQR 5-10) after introduction of
      the ERP (p < 0.001). No statistically significant differences in LOS were
      observed between elderly (>=80 years) and younger patients or between different
      BMI groups. American Society of Anesthesiologists (ASA) grade 3 patients
      demonstrated significantly longer median LOS than those with ASA grades 1 and 2.
      Patients undergoing laparoscopic surgery had median LOS of 6 days (IQR 4-8)
      compared to 7 days (IQR 5-10) for open procedures (p < 0.001). No differences in
      morbidity or mortality were observed between the groups. CONCLUSIONS: Unselected
      application of an ERP in our unit has been associated with reductions in post
      operative LOS. The ERP was safe and effective when applied to all our study
      patients independent of age and BMI. Despite LOS being longer in ASA grade 3
      patients, application of the ERP to this higher risk group was not associated
      with significantly increased morbidity or mortality. Laparoscopic surgery
      resulted in additional modest reductions in LOS compared to open surgery within
      the ERP.

PMID- 21843821
TI  - The management of solitary colorectal liver metastases.
AB  - Surgical resection of solitary colorectal liver metastases is associated with
      long-term survival. Radiofrequency ablation used as the primary treatment option
      of solitary resectable colorectal liver metastases is associated with an
      increased risk of local recurrence that generally leads to worse survival
      compared to resection. In contrast with treatment of other hepatic malignancies,
      radiofrequency ablation is not equivalent to resection for colorectal liver
      metastases and should not be used as an alternative but limited to inoperable
      patients. Although overall survival rate after resection can be up to 71% at 5
      years, the majority of patients develop recurrence. Preoperative chemotherapy
      contributes to decrease the risk of recurrence after resection of colorectal
      liver metastases. In patients with advanced solitary colorectal liver metastasis
      initially non suitable for resection, chemotherapy and portal vein embolization
      contribute to increase the number of surgical candidates whereas radiofrequency
      is rarely an option.

PMID- 21843822
TI  - A focus on surgical preoperative evaluation of the bariatric patient--the
      Cleveland Clinic protocol and review of the literature.
AB  - Bariatric surgery is well established as a safe and effective treatment for
      morbid obesity and related metabolic diseases. As an elective procedure, it is
      critical that individuals considering bariatric surgery should be carefully
      selected, extensively evaluated, and optimized in order to achieve optimal
      outcomes. This patient population has unique and challenging issues, including an
      extensive range of potential medical, psychiatric, and psychological
      comorbidities, and often patients have unrealistic expectations of the surgery.
      Therefore, a multidisciplinary, comprehensive and timely assessment
      preoperatively is of great importance. Individual bariatric units utilise
      different preoperative patient evaluation protocols. There is at present no
      uniformly accepted or recommended practice. In this article we describe what we
      believe are the essential components of a preoperative bariatric surgery
      evaluation, with supporting evidence for each recommendation. We also present a
      protocol currently in practice at a high volume bariatric center of excellence;
      the Bariatric and Metabolic Institute in the Cleveland Clinic, Ohio.

PMID- 21843823
TI  - A review of the relationship between alcohol and oral cancer.
AB  - This paper aims to review the current literature regarding the association
      between alcohol consumption and oral cancer. The authors have discussed the
      constituents of alcohol-containing beverages, the metabolism of ethanol and its
      effect on the oral microflora. The local and systemic carcinogenic effects of
      alcohol have been detailed. The beneficial effects of alcohol consumption on
      general health have also been considered. A possible relationship between alcohol
      containing mouthrinses and oral cancer has been suggested in the literature. The
      authors conclude that this relationship has not yet been firmly established.
      However, the use of alcohol-containing mouthrinses in high-risk populations
      should be restricted, pending the outcome of further research.

PMID- 21843824
TI  - Motion analysis as an outcome measure for hip arthroplasty.
AB  - We review the available literature on the use of motion analysis as an outcome
      measure following total hip arthroplasty. Several studies have investigated
      spatio-temporal parameters of gait, kinematics, kinetics and electromyographic
      outputs following hip arthroplasty. We undertook to review all these studies to
      evaluate the value of motion analysis as an outcome measure. The search of the
      literature yielded eight studies. Motion analysis demonstrates functional
      improvement in patients post-operatively, but the values of the variables
      measured do not reach the same levels as control subjects. Motion analysis does
      not show much difference post-operatively between patients operated on by
      different technique or incision. Furthermore, motion analysis can identify subtle
      functional limitations which may not be detectable with conventional outcome
      measures.

PMID- 21843825
TI  - Risk-adjusted scoring systems can predict surgeons' performance in colorectal
      surgery.

PMID- 21843828
TI  - Evidence-based practice: lost in translation?

PMID- 21843827
TI  - A devastating complication of 'skin popping'.

PMID- 21843829
TI  - Biofeedback improves activities of the lower limb after stroke: a systematic
      review.
AB  - QUESTION: Is biofeedback during the practice of lower limb activities after
      stroke effective in improving performance of those activities, and are any
      benefits maintained after intervention ceases? DESIGN: Systematic review with
      meta-analysis of randomised trials. PARTICIPANTS: People who have had a stroke.
      INTERVENTION: Biofeedback during practice of sitting, standing up, standing, or
      walking. OUTCOME MEASURES: Continuous measures of activity congruent with the
      activity trained. RESULTS: 22 trials met the inclusion criteria and 19 contained
      data suitable for analysis. Effect sizes were calculated as standardised mean
      differences because different outcome measures were used. Since inclusion of all
      trials produced substantial statistical heterogeneity, only trials with a PEDro
      score >4 (11 trials) were included in the final analysis (mean PEDro score 5.7).
      In the short-term, biofeedback improved lower limb activities compared with usual
      therapy/placebo (SMD=0.49, 95% CI 0.22 to 0.75). Lower limb activities were still
      improved compared with usual therapy/placebo 1 to 5 months after the cessation of
      intervention (SMD=0.41, 95% CI 0.06 to 0.75). CONCLUSION: Augmenting feedback
      through the use of biofeedback is superior to usual therapy/placebo at improving
      lower limb activities in people following stroke. Furthermore, these benefits are
      largely maintained in the longer term. Given that many biofeedback machines are
      relatively inexpensive, biofeedback could be utilised more widely in clinical
      practice.

PMID- 21843830
TI  - Home-based exercise improves the quality of life and physical function but not
      the psychological status of people with chronic heart failure: a randomised
      trial.
AB  - QUESTIONS: Are anxiety and depression correlated with physical function,
      disability, and quality of life in people with chronic heart failure? Does 8
      weeks of home-based exercise improve anxiety, depression, physical function,
      disability, and quality of life in these patients? Do the changes in these
      outcomes correlate? DESIGN: Randomised trial. PARTICIPANTS: 51 people with
      clinically stable chronic heart failure were randomised into an experimental
      group (n=24) or a control group (n=27). INTERVENTION: The experimental group
      undertook an individualised home-based exercise program, 30 minutes per session,
      3 sessions per week for 8 weeks, with regular telephone follow-up and
      consultations. The control group maintained their usual activity during this
      period. OUTCOME MEASURES: The Hospital Anxiety and Depression Scale, six-minute
      walk test, Groningen Activity Restriction Scale, and Minnesota Living with Heart
      Failure Questionnaire were administered at baseline and 8 weeks. RESULTS: At
      baseline, anxiety and depression were inversely moderately correlated with
      walking distance, activity, and quality of life. Compared with controls, the
      experimental group improved significantly more in their walking distance (by 21m,
      95% CI 7 to 36) and their quality of life (by 7 points on the 105-point Minnesota
      score, 95% CI 1 to 12). In the experimental group, the changes in quality of life
      correlated moderately strongly with changes in anxiety (r=0.539, p=0.01).
      CONCLUSIONS: Anxiety and depression were associated with physical function,
      disability, and quality of life in people with chronic heart failure. Home-based
      exercise improved quality of life and physical function significantly but not
      psychological status in these patients.

PMID- 21843831
TI  - Localised application of vibration improves passive knee extension in women with
      apparent reduced hamstring extensibility: a randomised trial.
AB  - QUESTION: Does the localised application of vibration over the hamstrings improve
      hamstring extensibility? DESIGN: Randomised controlled trial with concealed
      allocation, intention-to-treat analysis, and assessor blinding. PARTICIPANTS: 30
      non-athletic females (aged 18-22 yrs) with limited hamstring extensibility
      bilaterally. INTERVENTION: The experimental group received 3 sessions of
      localised application of vibration per week for 8 weeks. At each session, 3 sets
      of vibration were applied over the left and right hamstring muscles. The control
      group continued their usual daily activities. Both groups were asked to perform
      no specific exercises during the 8-week intervention period. OUTCOME MEASURES:
      Hamstring muscle extensibility was measured bilaterally at baseline and at the
      end of the 8-week intervention period by measuring passive knee extension in
      supine with 90 deg of hip flexion. RESULTS: At baseline, the mean lack of knee
      extension was 27 deg (SD 9) in the experimental group and 24 deg (SD 8) in the
      control group. At 8 weeks, this had changed to 13 deg (SD 5) in the experimental
      group and 23 deg (SD 9) in the control group. This was a significant treatment
      effect: mean between-group difference of 13 deg (95% CI 11 to 16). CONCLUSION: An
      8-week regimen of localised application of vibration over the hamstring muscles
      significantly reduces knee extension lack in women with reduced range on the
      passive knee extension test.

PMID- 21843832
TI  - Twenty minutes of passive stretching lowers glucose levels in an at-risk
      population: an experimental study.
AB  - QUESTION: Can passive static stretching lower blood glucose in an at-risk
      population? DESIGN: Randomised, within-participant experimental study.
      PARTICIPANTS: 22 adults (17 males) either at increased risk of Type 2 diabetes or
      with Type 2 diabetes. INTERVENTION: The participants reported to the laboratory
      2hr after eating a meal, and drank 355ml of fruit juice (~43g carbohydrate).
      Thirty minutes later, they underwent either a 40min passive static stretching
      regimen or a mock passive stretching regimen. Stretching consisted of six lower
      body and four upper body static passive stretches. For the mock stretches, the
      same positions were adopted, but no tension was applied to the musculature.
      OUTCOME MEASURES: Blood glucose levels for both the stretching and mock
      stretching were analysed from a finger prick sample using a hand-held glucometer.
      Values were obtained at baseline (0min), during the regimen (20min), and after
      the regimen (40min) on both study days. RESULTS: Compared to mock stretch,
      stretching resulted in a significantly greater drop in blood glucose at 20min
      (mean difference 28mg/dL, 95% CI 13 to 43; or 1.57mmol/L, 95% CI 0.72 to 2.39).
      This effect was also statistically significant at 40min (mean difference 24mg/dL,
      95% CI 9 to 39; or 1.35mmol/L, 95% CI 0.50 to 2.17). CONCLUSION: These results
      suggest that passive static stretching of the skeletal muscles may be an
      alternative to exercise to help lower blood glucose levels.

PMID- 21843833
TI  - Musculoskeletal pain is prevalent among recreational runners who are about to
      compete: an observational study of 1049 runners.
AB  - QUESTION: What is the prevalence and nature of musculoskeletal pain in
      recreational runners immediately before a race? DESIGN: Cross-sectional survey.
      PARTICIPANTS: Adults intending to compete in a recreational running race between
      5000 and 10 000 metres. MEASURES: Demographic data collected about the
      respondents included: age, gender, height, weight, duration of running
      experience, distance run per week, number of training sessions per week, training
      surface, and use of coaching. Respondents were asked if they had any pain. If
      pain was present, data were collected regarding its location, duration, current
      intensity, and behaviour. All data were self-reported. RESULTS: Data were
      collected from 1049 runners at five recreational races in Sao Paulo, Brazil. Of
      these respondents, 227 (22%) reported musculoskeletal pain before the race. Male
      respondents reported a greater running experience, a higher distance run per
      week, and a greater body mass index. Despite this, the prevalence of pain was 20%
      among the 796 male respondents and 27% among the 253 female respondents (RR 1.35,
      95% CI 1.05 to 1.72). Where pain was present, it was typical of overuse injuries
      and its duration, intensity, and behaviour were similar between male and female
      respondents. CONCLUSION: The prevalence of musculoskeletal pain in recreational
      runners about to compete is substantial. Physiotherapists might be able to
      circumvent worsening of existing overuse injuries in this population with advice
      and preventive interventions.

PMID- 21843834
TI  - Lack of perceived benefit and inadequate transport influence uptake and
      completion of pulmonary rehabilitation in people with chronic obstructive
      pulmonary disease: a qualitative study.
AB  - QUESTION: What prevents people with chronic obstructive pulmonary disease (COPD)
      from attending and completing pulmonary rehabilitation programs? DESIGN:
      Qualitative design using semi-structured interviews. PARTICIPANTS: 19 adults with
      COPD who had declined to participate and 18 adults with COPD who had not
      completed a pulmonary rehabilitation program at a metropolitan teaching hospital.
      RESULTS: A lack of perceived benefit from pulmonary rehabilitation was a
      significant theme for those who chose not to participate in pulmonary
      rehabilitation. Participants expressed perceptions that exercise was not a
      worthwhile treatment, or that they were already doing enough exercise at home.
      Difficulty getting to the program related to poor mobility, lack of transport,
      and cost of travel was a significant theme, expressed both by those who chose not
      to participate and those who did not complete. Another major theme associated
      with both uptake and completion involved being unwell, with participants
      indicating that the burden of COPD and other comorbidities impacted on
      attendance. Minor themes involved competing demands on time, older age, fatigue,
      program timing, and lack of social support. CONCLUSION: Many people with COPD who
      elect not to take up a referral to pulmonary rehabilitation perceive that they
      would not experience any health benefits from attendance. Difficulties with
      travel to the program and being unwell are barriers to both uptake and
      completion. Improving attendance at pulmonary rehabilitation requires
      consideration of how information regarding the proven benefits of pulmonary
      rehabilitation can be conveyed to eligible patients, along with flexible program
      models that facilitate access and accommodate co-morbid disease.

PMID- 21843835
TI  - Foot orthoses can reduce lower limb overuse injury rate.

PMID- 21843836
TI  - Resistance training preserves skeletal muscle function in patients with COPD who
      are hospitalised with an acute exacerbation.

PMID- 21843837
TI  - Lateral wedge insoles worn for 12 months provided no symptomatic or structural
      benefit for people with medial knee osteoarthritis.

PMID- 21843838
TI  - Rehabilitative ultrasound imaging.
AB  - Neuromuscular deficits have been linked with chronic musculoskeletal conditions.
      The use of ultrasound imaging(USI) to aid rehabilitation of neuromusculoskeletal
      disorders has been called rehabilitative ultrasound imaging (RUSI)and defined as
      'a procedure used by physical therapists to evaluate muscle and related soft
      tissue morphology and function during exercise and physical tasks. RUSI is used
      to assist in the application of therapeutic interventions,providing feedback to
      the patient and physical therapist (Teyhen 2006). Brightness mode (b-mode) USI is
      the most common form used by physical therapists and will be the focus of this
      summary. CLINICAL UTILITY: USI can distinguish between healthy adults and those
      with low back pain (LBP). Those with LBP have decreased muscle thickness, side-to
      side asymmetry,and decreased ability to thicken the muscles during a contraction
      (Teyhen et al 2009). Moreover, when measured by USI, lumbar multifidus muscle
      asymmetry appears to be predictive of future episode of LBP up to three years
      later(Hides et al 2001). Finally, USI can distinguish between changes in muscle
      thickness during common LBP exercises when performed by healthy adults (Teyhen et
      al 2008) and is preliminarily supported as a biofeedback tool to enhance exercise
      effectiveness (Henry and Teyhan 2007). CRITERION-RELATED VALIDITY: In a recent
      systematic review Koppenhaver et al (2009a) concluded that b-mode USI when
      applied in a rehabilitative setting is a valid tool to measure trunk muscle size
      and muscle activation during most submaximal contracted states. When comparing
      muscle thickness obtained by magnetic resonance imaging and USI, researchers have
      demonstrated substantial agreement(ICC 0.84 to -0.95) with only minimal
      differences between the modalities (0.03 to 0.21 cm2) (Hides et al 1995, 2006).
      Although comparisons between electromyography and change in muscle thickness
      obtained by USI have most often demonstrated a curvilinear relationship (Hodges
      et al 2003), the ability of USI to measure muscle activation is likely context
      dependent and is based on the muscle being measured, the task performed, and the
      intensity of the contraction (Koppenhaver et al 2009a). RESPONSIVENESS TO CHANGE:
      Motor control training has been demonstrated to increase multifidus cross
      sectional area (p = 0.004), decrease side-to-side asymmetry, and was associated
      with a 50% reduction in pain (Hides et al 2008b).Additionally, recent evidence
      suggests increased contracted thickness of the lumbar multifidus one week after a
      spinal manipulation was predictive of larger improvements in low back pain
      related disability (Koppenhaver et al 2011).The minimal amount of change
      associated with clinical improvement has yet to be determined. RELIABILITY: In a
      recent systematic review Hebert et al (2009)concluded that the majority of high
      quality studies indicated that RUSI has good intrarater and inter-rater
      reliability (ICC> 0.90). The standard error of measurement was decreased by
      nearly 25% when using a mean of two measures and by 50% when using a mean of
      three measures (Koppenhaver et al 2009b). Novice raters, when properly trained,
      can assess the trunk muscles reliably (ICC 0.86 to 0.94) (Teyhen et al 2011).
      INFLUENCE OF SEX AND BODY MASS INDEX: Muscle thickness and cross sectional area
      is greater in males than females and is associated with increased body mass index
      (Teyhenet al 2007).

PMID- 21843839
TI  - Shoulder Pain and Disability Index (SPADI).
AB  - The Shoulder Pain and Disability Index (SPADI) was developed to measure current
      shoulder pain and disability in an outpatient setting. The SPADI contains 13
      items that assess two domains; a 5-item subscale that measures pain and an 8-item
      subscale that measures disability. There are two versions of the SPADI; the
      original version has each item scored on a visual analogue scale (VAS) and a
      second version has items scored on a numerical rating scale (NRS). The latter
      version was developed to make the tool easier to administer and score (Williams
      et al 1995). Both versions take less than five minutes to complete (Beaton et al
      1996, Williams et al 1995). The questionnaire was developed and initially tested
      in a mixed diagnosis group of male patients presenting to ambulatory care
      reporting shoulder pain (Roach et al 1991). The SPADI has since been used in both
      primary care on mixed diagnosis (Beaton et al 1996, MacDermaid et al 2006) and
      surgical patient populations including rotator cuff disease (Ekeberg et al 2008),
      osteoarthritis, and rheumatoid arthritis (Christie et al 2010), adhesive
      capsulitis (Staples et al 2010, Tveita et al 2008), joint replacement surgery
      (Angst et al 2007), and in a large population-based study of shoulder symptoms
      (Hill et al 2011). The SPADI is available free of charge at several sites, eg,
      www.workcover.com/public/download.aspx?id=799. INSTRUCTIONS TO THE CLIENT AND
      SCORING: In the original version the patient was instructed to place a mark on
      the VAS for each item that best represented their experience of their shoulder
      problem over the last week (Roach et al 1991). Each subscale is summed and
      transformed to a score out of 100. A mean is taken of the two subscales to give a
      total score out of 100, higher score indicating greater impairment or disability.
      In the NRS version (Williams et al 1995) the VAS is replaced by a 0-10 scale and
      the patient is asked to circle the number that best describes the pain or
      disability. The total score is derived in exactly the same manner as the VAS
      version. In each subscale patients may mark one item only as not applicable and
      the item is omitted from the total score. If a patient marks more than two items
      as non applicable, no score is calculated (Roach et al 1991). RELIABILITY AND
      VALIDITY: Reproducibility of the SPADI in the original description was poor, with
      an intraclass correlation coefficient (ICC) of 0.66. A more recent systematic
      review has found reliability coefficients of ICC >= 0.89 in a variety of patient
      populations (Roy et al 2009). Internal consistency is high with Cronbach alpha
      typically exceeding 0.90 (Roy et al 2009, Hill et al 2011). The SPADI
      demonstrates good construct validity, correlating well with other region-specific
      shoulder questionnaires (Paul et al 2004, Bot et al 2004, Roy et al 2009). It has
      been shown to be responsive to change over time, in a variety of patient
      populations and is able to discriminate adequately between patients with
      improving and deteriorating conditions (Beaton et al 1996, Williams et al 1995,
      Roy et al 2009). No large floor or ceiling effects for the SPADI have been
      observed (Bot et al 2004, Roy et al 2009). The minimal clinically important
      difference has been reported to be 8 points; this represents the smallest
      detectable change that is important to the patient (Paul et al 2004). When the
      SPADI is used more than once on the same subject, eg, at initial consultation and
      then at discharge, the minimal detectible change (MDC 95%) is 18 points (Angst et
      al 2008, Schmitt et al 2004). Thus some caution is advised with regard to
      repeated use of the instrument on the same patient. A change score of less than
      this value could be attributed to measurement error.

PMID- 21843843
TI  - [General practitioners between individual and population medicine].

PMID- 21843844
TI  - [Check up 35: what benefits do general practitioners in Brandenburg see?].
AB  - INTRODUCTION: The so-called "Check up 35" is a structured preventive examination
      to be conducted by primary care providers. Recent interviews have shown that
      expectations with regard to this examination vary among physicians; some of them
      expressed doubt that the consultation is useful at all. The aim of this study was
      to representatively examine Brandenburg's family physicians' attitudes towards
      this "Check up". METHODS: 50% of the family physicians listed in the data base of
      the Association of SHI Physicians were randomly selected to receive a mail
      questionnaire (n=748). Participation in the study was voluntary, the
      questionnaires were evaluated anonymously. The physicians were asked about both
      content and assumed benefit of consultations. RESULTS: The questionnaire was
      answered by 37% of the physicians (n=274). In 2008, 40 "Check ups" were conducted
      every three months. 96% of the physicians amended the standard programme with
      additional preventive examinations - most frequently serum creatinine
      measurements. In most of the respectively rated categories, they appreciate the
      usefulness of the examination. In contrast, they take a rather sceptical attitude
      towards the en bloc standard programme. DISCUSSION: The study shows that many
      family physicians are very critical of the "Check up 35"; in particular, this
      applies to the range of scheduled examinations. There are considerable variations
      in the individual shaping of the consultation process among the physicians. They
      use the "Check up" as a tool for individual prevention instead of limiting it to
      the reduced standardised screening as intended.

PMID- 21843845
TI  - [General practitioners' opinion and attitude towards DMPs and the change in
      practice routines to implement the DMP "diabetes mellitus type 2"].
AB  - BACKGROUND: Effective implementation of disease management programmes (DMPs) in
      primary care practices often requires changes in practice workflows and
      responsibilities and acceptance by the parties involved. Within the ELSID study
      (evaluation study of the DMP diabetes mellitus type 2) the physicians' attitudes
      toward DMPs were obtained and an optimised implementation of DMPs was developed
      by conducting a quality management cycle with primary care practice teams. The
      aim was to investigate which practice workflows will have to be changed and what
      kind of barriers to implement these changes are perceived. METHODS: In 78 primary
      care practices of the two German federal states of Rheinland-Pfalz and Sachsen
      Anhalt a quality management cycle was conducted using a structured analysis of
      the current state of DMP workflows and the need for improvement identified.
      Subsequently, an optimised workflow was developed and targets were agreed upon.
      After 6 months, the study team called to inquire about the current state of
      implementation and, if appropriate, actual barriers to change. RESULTS: After 6
      months, 71 practices had been interviewed by phone. 64 of them (90.1%) had agreed
      on at least one target (e.g., to purchase new instrumentation, to regularly
      discuss feedback reports, to set up a patient registry). On average three targets
      had been formulated, and 2 out of 3 had been implemented in the meantime. In most
      cases lack of time was given as the reason for non-implementation. CONCLUSIONS:
      The majority of surveyed practices perceived some need for improvement. But
      sufficient resources (time, staff and money) are required to ensure efficient
      implementation of DMPs in primary care practices and their integration with
      routine processes. A redefinition of responsibilities for DMPs will strengthen
      the role of medical assistants and promote high-quality implementation of these
      programmes.

PMID- 21843847
TI  - [Which criteria affect the cooperation between general practitioners and
      specialists in ambulatory care? A qualitative study about general practitioners'
      perception].
AB  - BACKGROUND: Good cooperation between physicians is an essential requirement for
      quality health care. General practitioners (GPs) have a key role in coordinating
      the various levels of care and physician contacts. Within the scope of the
      "InteraKtion" study of the Competence Centre of General Practice Baden
      Wuerttemberg GPs were interviewed about their experiences and opinions regarding
      their cooperation with specialists. The aim of this study was to identify
      criteria and barriers of the referral process. METHODS: 22 semi-structured
      interviews were conducted among GPs in Heidelberg, Tuebingen and Ulm. Data
      analysis was carried out using ATLAS.ti according to the qualitative content
      analysis by P. Mayring. RESULTS: From the GPs' point of view, the criteria for
      referral to specialists include: specialists' medical skills, good doctor-patient
      relationship and patient satisfaction. In addition, the willingness to arrange
      short-term appointments in urgent cases, timely diagnosis and adequate
      communication were mentioned. The following barriers were pointed out: long
      appointment wait times and the specialists' increased provision of Individual
      Healthcare Services. CONCLUSION: These results indicate that GPs have clear
      criteria for referral to specialists. These findings should find their way into
      future quantitative studies to explore the weighting of the criteria and barriers
      discussed here. Joint training activities or quality circles could improve the
      personal contact between GPs and specialists working in the same region.

PMID- 21843846
TI  - [Practice-based home visit and telephone monitoring of chronic heart failure
      patients: rationale, design and practical application of monitoring lists in the
      HICMan trial].
AB  - BACKGROUND: Patients with chronic heart failure have complex care needs which can
      be addressed by case management interventions. Monitoring lists for heart failure
      were developed and tested as part of a trial evaluating primary care-based case
      management of patients with heart failure (HICMan). METHOD: Design and
      characteristics of the monitoring lists used during the HICMan trial are
      described in order to evaluate technical feasibility and time expenditure. In a
      secondary analysis of data from the HICMan trial descriptive statistics were
      used. RESULTS: Two checklists were developed on the basis of evidence-based
      guidelines to regularly monitor heart failure patients by phone and home visits.
      These checklists contain questions about heart failure symptoms and signs
      (precursors) of clinical deterioration. Ninety-seven heart failure patients (64
      NYHA class I/II, 33 NYHA class III) were monitored for 12 months. Eighteen
      critical incidents like acute angina pectoris or acute dyspnoea occurred during
      the study, two of them leading to immediate hospital admissions. Patients with
      NYHA class III had significantly more potentially clinically relevant incidents
      than patients with NYHA class I/II. Mean [SD, range] time expenditure for
      telephone monitoring was 10min [+/- 5min, 2 to 38min], for home visits 53min [+/-
      13min, 18 to 90min]. Both monitoring lists appeared to be plausible and feasible
      tools for the primary care-based case management of heart failure patients.

PMID- 21843848
TI  - [Domestic violence in patients - underestimated by medical staff: self-report
      data from medical staff of the outpatient clinical settings in Dresden and
      Chemnitz and of the inpatient departments of the Medical University of Dresden in
      Saxony, Germany].
AB  - Medical staffs have a key role in the adequate treatment of victims of domestic
      violence. The present study collects self-report data about subjective
      perception, general knowledge and motivation for further training about domestic
      violence from medical staff of inpatient and outpatient clinical settings. A
      questionnaire was developed and sent to doctors, nursing staff, midwives, and
      psychotherapists working in outpatient clinical settings in Dresden and Chemnitz
      and in the inpatient departments of the Medical University of Dresden in Saxony,
      Germany. 1,107 (23%) of 4,886 distributed questionnaires were returned and
      analysed. The participants reported that they were seldom confronted with the
      consequences of domestic violence in their clinical practice. The unawareness
      among staff in specialised care facilities and advisory centres was highly
      noticeable. More than 90% of the participants did not know the main advisory
      centre for victims of domestic violence. Even if some facilities were known there
      was virtually no contact. The majority was not satisfied with the level of
      support they were able to offer. Further difficulties pointed out by participants
      included lack of time and the assumption that victims were unwilling to answer
      questions about domestic violence. The participants also expressed a high demand
      for further training.

PMID- 21843850
TI  - Reporting quality of conference abstracts on randomised controlled trials in
      gerontology and geriatrics: a cross-sectional investigation.
AB  - Without transparent reporting of how a randomised controlled trial was designed
      and conducted and of the methods used, its internal validity cannot be assessed
      by the reader. A congress abstract is often the only source providing information
      about a trial. In January 2008, an extended CONSORT statement on abstract
      reporting was published. Its impact has yet to be evaluated. Using a slightly
      modified CONSORT checklist comprising 17 items, we thus investigated the
      reporting quality of randomised controlled trials published in the book of
      abstracts presented at the World Congress of Geriatrics and Gerontology in Paris
      in July 2009. A total of n=4,416 abstracts was screened for inclusion; n=129 met
      the inclusion criteria. The overall quality of the abstracts was remarkably poor.
      The primary outcome was mentioned in 34/129 abstracts (26%), none of the
      abstracts reported on the procedure of random allocation of participants or
      clusters, 21/129 abstracts (16%) reported some kind of blinding, and the
      attrition rate was mentioned in only 12/129 abstracts (9%). The majority of
      abstracts fulfilled two items: description of intended intervention for each
      group (102/129; 79%) and general interpretation of results (107/129; 83%). Trial
      status was reported in all abstracts. Both journal editors and committees
      organising congresses are requested to define the use of the CONSORT statement as
      a prerequisite in their guidelines for authors and to instruct reviewers to
      conduct compliance checks. Medical associations should finally endorse the
      indispensability of the CONSORT statement and publish it in their journals.
      Otherwise the intended benefits cannot be fully generated.

PMID- 21843851
TI  - [Graphic synopsis of implementation of German guideline clearing reports in
      national disease management guidelines].
AB  - BACKGROUND: While methods for the production of guidelines (evidence analysis,
      assessment, adaptation) have been continually refined throughout the past years,
      there is a lack of instruments for the production of easily understandable
      synopses. METHODS: Definition of a methodological approach to encompass synopses
      by Spidernet diagrams. RESULTS: Tables of synopses can be generated with distinct
      information to bring down the main results in one Spidernet diagram. This is
      possible for both the entire synopsis and parts of it. DISCUSSION: Guideline
      comparisons require detailed analyses on the one hand and easily understandable
      presentations of their results on the other. CONCLUSION: Guideline synopses can
      be substantially supported by graphic presentation of the results of synopsis.
      Graphic synopsis is also helpful in other cases; it may be used, for example, to
      summarise HTA reports, systematic reviews or guidelines.

PMID- 21843852
TI  - [Effects of guideline-compliant therapy on the survival of primary breast cancer
      patients with: results of a retrospective cohort study].
AB  - PURPOSE: The development and implementation of the "Interdisciplinary S3
      Guideline for the Diagnosis, Treatment and Follow-up Care of Breast Cancer" (3)
      is intended to optimise national health services. This guideline already serves
      both as a basis for the certification of German breast centres and for the
      external comparative quality assurance based on guideline based quality
      indicators. Nevertheless, the effects of the implementation on relevant outcomes
      have not been examined so far. METHODS: The retrospective cohort study analyses
      data of 3,976 female patients with primary breast cancer which were collected at
      the University of Ulm and co-operating certified breast centres between 2001 and
      2005. Based on the S3 guideline, an analysis model was developed to allow for the
      examination of guideline-adherent therapy on the basis of the guideline
      recommendations, and the effects of guideline-adherent compared to not guideline
      adherent therapy on overall (OAS) and recurrence-free survival (RFS) were
      examined subsequently. RESULTS: In total, 2,063 (51.9%) of the 3,976 patients
      were treated in adherence the guideline. In 1,913 (48.1%) patients deviations
      from the guideline recommendations in at least one of the therapeutic options
      were found. The variable "guideline-adherent treatment" had significant influence
      on RFS [p < 0.001; HR=2.20; 95% CI (1.74 to 2.79)] and OAS (p < 0.001; HR=2.57;
      95% CI (1.96 to 3.37)], each adjusted for age, tumour size, nodal status and
      grading. RFS decreases with the number of deviations from guideline
      recommendations [1 to 2 deviations: p < 0.001; HR=2.04; 95% CI (1.60 to 2.60); >=
      3 deviations: p < 0.001; HR=3.64; 95% CI (2.43 to 5.45), also adjusted for age,
      tumour size, nodal status and grading]. Similar results were found for the OAS.
      CONCLUSION: Patients with breast cancer should be treated in adherence to
      guideline recommendations. Deviations and barrier factors will have to be
      evaluated in the future in order to further optimise both the guideline and
      guideline-adherent therapy.

PMID- 21843853
TI  - [Quinth - the quality indicator thesaurus of the Statutory Health Insurance Funds
      Association].

PMID- 21843854
TI  - [Opinion of medical students and medical faculty of the University of Ulm weekend
      seminar "Appraisal of the value of health services", 13 -15 May, 2011 on the
      "Good practice health information" article].

PMID- 21843856
TI  - Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca
      (Hajj) 1432 (2011).

PMID- 21843857
TI  - Fever, fever patterns and diseases called 'fever'--a review.
AB  - Fever is a prominent feature of disease since antiquity. The febrile response is
      orchestrated by the central nervous system through endocrine, neurological,
      immunological and behavioural mechanisms. Other than a regulated rise in body
      temperature, fever is often accompanied by various sickness behaviours, changes
      in metabolic and physiological characteristics of body systems and alterations in
      immune responses. Fever and the febrile response, therefore, remain significant
      contributors to the pathogenesis, clinical presentation and outcome of many
      illnesses and diseases. This review highlights the pathophysiology of the febrile
      response and describes the fever types and patterns, including their clinical
      significance. The various medical illnesses called "fever" are also listed and
      the origins of their appellations discussed.

PMID- 21843858
TI  - Protection of medical and paramedical university students in Lebanon against
      measles, mumps, rubella and varicella: active measures are needed.
AB  - OBJECTIVE: In many countries, universities require students to either show a
      physician-certified proof of immunity or to get vaccinated against measles,
      mumps, rubella and varicella, prior to their registration in medical and
      paramedical majors. The objective of this study was to evaluate the need to
      implement this policy in Lebanon. DESIGN: A cross-sectional study was performed
      on students of the Lebanese University (LU), faculties of Medicine, Dentistry,
      Pharmacy and Public Health. METHODS: The serological immunity status was assessed
      by determining specific antibody titer and the disease and vaccination history of
      502 students was collected. Based on percentages of susceptibility, a cost
      effectiveness analysis was performed to compare systematic vaccination without
      prior serological testing with selective vaccination of seronegative students.
      RESULTS: Percentages of individuals with serologically confirmed immunity against
      varicella, measles, rubella and mumps were 93%, 86%, 88% and 75% respectively,
      and 42% of the students were susceptible to at least one of the pathogens covered
      by the MMR vaccine. Compilation of 186 vaccination records indicated that only 19
      students (10%) had been adequately vaccinated. Moreover, among those, 7 students
      (37%) were still unprotected against at least one virus. Systematic vaccination
      against MMR was found to be 4-5 times less expensive than selective vaccination,
      while selective vaccination of seronegative individuals was more cost-efficient
      for varicella. CONCLUSION: Since, in this population, very few individuals were
      able to present a proof of adequate vaccination, it is recommended to
      systematically vaccinate healthcare students in Lebanon against MMR. For
      varicella, selective vaccination after serological testing should be performed.

PMID- 21843859
TI  - A study of Helicobacter pylori outer-membrane proteins (hom) A and B in Iraq and
      Turkey.
AB  - Helicobacter pylori outer-membrane proteins (hom), especially the homB gene, have
      been suggested as a novel virulence factor. However, no study has been conducted
      in Middle Eastern countries regarding the association between these genes and
      clinical outcome. Gastric biopsies were obtained from 70 and 64 unselected H.
      pylori+ patients from Iraq and Turkey, respectively. PCR was performed to study
      the presence of the homA, homB, and cagA. No association was found between homA
      or homB and clinical outcomes. When Iraqi and Turkish strains were combined as
      Middle Eastern samples, cagA positivity was significantly higher in patients with
      peptic ulcer disease (PUD) than those with non-peptic ulcer disease (NPUD)
      (p=0.003, OR=3.6, CI=1.5-8.8). Two Iraqi strains showed intermediate, non-homA
      non-homB, length PCR products. The function of such gene is yet to be determined.
      In conclusion, hom genes might not be a good indicator for disease prediction in
      the Middle East. More studies are needed to confirm these results and determine
      the function of intermediate length hom.

PMID- 21843860
TI  - Diabetes mellitus and HIV as co-morbidities in tuberculosis patients of rural
      south India.
AB  - OBJECTIVES: Incidence of tuberculosis (TB) is greatest among patients with
      impaired immunity. India is experiencing a double epidemic of HIV and diabetes
      mellitus (DM), both of which are strongly associated with immuno-suppression.
      This study aimed to discover the prevalence of HIV and DM in both the pulmonary
      and extra-pulmonary TB patients of rural south India, retrospectively. METHODS:
      Medical records of 192 microbiologically diagnosed pulmonary TB and 37 extra
      pulmonary TB patients were thoroughly studied and data were extracted. The
      frequency distribution of HIV and DM was evaluated along with other demographic
      details such as age, sex and occupation in both groups. RESULTS: The mean age of
      the pulmonary TB patients was 41.11+/-15.7 years, with significantly higher
      (p<0.0001) preponderance of DM (31.8%) over HIV (8.9%). 72.13% of the diabetic
      patients belonged to the age group of 41-60 years. Extra-pulmonary TB patients
      had a mean age of 34.62+/-12.9, years with a significantly higher (p<0.006) HIV
      prevalence of 32.43% over DM (5.4%). 75% of the HIV patients belonged to the age
      group of 41-60 years. Occupationally, the majority of the pulmonary TB patients
      were agricultural labourers (25.2%) while the majority of the extra-pulmonary TB
      patients were housewives or self employed (18.92%). CONCLUSION: Though more
      importance is being given to HIV-TB coinfection, we cannot overlook DM, which
      showed a significantly higher prevalence in pulmonary TB patients compared to
      HIV. The rising prevalence of DM in high TB burden countries may adversely affect
      TB control.

PMID- 21843861
TI  - Panton-Valentine Leukocidin associated Staphylococcus aureus infections in
      London, England: clinical and socio-demographic characterisation, management,
      burden of disease and associated costs.
AB  - Routine notification of Staphylococcus aureus producing the Panton-Valentine
      Leucocidin toxin (PVL-SA) to the North East & Central London Health Protection
      Unit, a communicable disease control unit covering a population of 2.8 million,
      identified 115 cases in 2009-2010, including 99 skin and soft tissue infections
      (SSTIs), 15 severe infections and one asymptomatic colonisation. Most cases
      occurred in children and young adults, unequally distributed geographically and
      socio-economically. The majority of infections were community acquired and 60%
      were caused by methicillin resistant strains. Overall, 27% of cases had previous
      SSTIs, and 32% had contacts with SSTIs suggestive of PVL-SA albeit these were not
      confirmed microbiologically. This suggests that characteristics of PVL-SA
      infection in cases and their families are not recognised as such leading to delay
      in diagnosis and low case ascertainment. A lack of governance around effective
      case management may also be contributing to the burden of disease. Further
      studies are recommended to evaluate key aspects of PVL-SA management including
      the effectiveness of decolonisation in the elimination of carriage and prevention
      of local spread.

PMID- 21843862
TI  - Fulminant hepatitis in typhoid fever.
AB  - AIM: To report a patient with typhoid fever who presented with fulminant
      hepatitis and was found to have a co-infection with hepatitis A. CASE: An 11-year
      old girl presented with fever and jaundice after arrival from India. Her blood
      culture was positive for Salmonella typhi. While on treatment with ceftriaxone,
      she had worsening of her jaundice with abrupt elevation of liver transaminases
      associated with coagulopathy. She was found to have an associated hepatitis A
      infection. Liver enzymes all reverted back to normal upon follow up. CONCLUSION:
      The association of typhoid fever with hepatitis A can result in fulminant
      hepatitis but in this case, is associated with complete recovery.

PMID- 21843863
TI  - Covalent coercion by Legionella pneumophila.
AB  - Adenylylation of Rab proteins appears to be an intriguing mechanism that
      Legionella pneumophila uses to modulate their activity during infection. Now the
      reverse reaction (deadenylylation) (Neunuebel et al., 2011; Tan and Luo, 2011)
      and a new posttranslational modification (phosphocholination) of Rab1 (Mukherjee
      et al., 2011) have been reported.

PMID- 21843864
TI  - Alphavirus entry: NRAMP leads the way.
AB  - The identity of the receptors that mediate alphavirus entry into host cells has
      been elusive. In this issue of Cell Host & Microbe, Rose et al. (2011) use a
      Drosophila RNAi screen to identify NRAMP, an iron transporter with 12
      transmembrane domains, as a receptor for Sindbis virus in both insect and
      mammalian cells.

PMID- 21843865
TI  - Candida albicans adds more weight to iron regulation.
AB  - The pathogen Candida albicans can occupy both the bloodstream and
      gastrointesintal (GI) tract, niches that differ in iron availability. Chen et al.
      report that a distinct transcription factor, Sef1, alters the conserved fungal
      iron regulatory paradigm. Sef1 is pivotal for bloodstream infection, but
      contributes to GI tract colonization as well.

PMID- 21843866
TI  - Tick salivary proteins offer the lyme disease spirochetes an easy ride and
      another way to hide.
AB  - The ability of the Lyme disease spirochetes to establish an infection in mammals
      is dependent in part on proteins of tick origin. Schuijt et al. (2011)
      investigate the role of the tick-derived protein, TSLPI, in spirochete
      transmission and in the evasion of killing by the lectin complement pathway.

PMID- 21843867
TI  - Natural resistance-associated macrophage protein is a cellular receptor for
      sindbis virus in both insect and mammalian hosts.
AB  - Alphaviruses, including several emerging human pathogens, are a large family of
      mosquito-borne viruses with Sindbis virus being a prototypical member of the
      genus. The host factor requirements and receptors for entry of this class of
      viruses remain obscure. Using a Drosophila system, we identified the divalent
      metal ion transporter natural resistance-associated macrophage protein (NRAMP) as
      a host cell surface molecule required for Sindbis virus binding and entry into
      Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus
      infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated
      binding and infection of Sindbis virus into mammalian cells, and murine cells
      deficient for NRAMP2 were nonpermissive to infection. Alphavirus glycoprotein
      chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis
      virus entry. Given the conserved structure of alphavirus glycoproteins, and the
      widespread use of transporters for viral entry, other alphaviruses may use
      conserved multipass membrane proteins for infection.

PMID- 21843868
TI  - Drifting motions of the adenovirus receptor CAR and immobile integrins initiate
      virus uncoating and membrane lytic protein exposure.
AB  - Viral particle binding to plasma membrane receptors elicits virus motions,
      recruits signaling proteins, and triggers membrane bending and fission, finally
      resulting in endocytic virus uptake. Here we analyze how human adenovirus engages
      its receptor coxsackievirus adenovirus receptor (CAR) and coreceptor alphav
      integrin to move on the plasma membrane. Virus binding to CAR through fiber knobs
      gave rise to diffusive motions and actomyosin-2-dependent drifts, while integrin
      targeted viruses were spatially more confined. Diffusions, drifts, and confined
      motions were specifically observed with viral particles that were subsequently
      internalized. CAR-mediated drifts together with integrin binding supported fiber
      shedding from adenovirus particles, leading to exposure of the membrane-lytic
      internal virion protein VI and enhanced viral escape from endosomes. Our results
      show that adenovirus uncoating is initiated at the plasma membrane by CAR
      drifting motion and binding to immobile integrins.

PMID- 21843869
TI  - An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans
      commensalism and pathogenesis.
AB  - The mammalian gastrointestinal tract and bloodstream are highly disparate
      biological niches that differ in concentrations of nutrients such as iron.
      However, some commensal-pathogenic microorganisms, such as the yeast Candida
      albicans, thrive in both environments. We report the evolution of a transcription
      circuit in C. albicans that controls iron uptake and determines its fitness in
      both niches. Our analysis of DNA-binding proteins that regulate iron uptake by
      this organism suggests the evolutionary intercalation of a transcriptional
      activator called Sef1 between two broadly conserved iron-responsive
      transcriptional repressors, Sfu1 and Hap43. Sef1 activates iron-uptake genes and
      promotes virulence in a mouse model of bloodstream infection, whereas Sfu1
      represses iron-uptake genes and is dispensable for virulence but promotes
      gastrointestinal commensalism. Thus, C. albicans can alternate between genetic
      programs conferring resistance to iron depletion in the bloodstream versus iron
      toxicity in the gut, and this may represent a fundamental attribute of
      gastrointestinal commensal-pathogens.

PMID- 21843870
TI  - A tick mannose-binding lectin inhibitor interferes with the vertebrate complement
      cascade to enhance transmission of the lyme disease agent.
AB  - The Lyme disease agent Borrelia burgdorferi is primarily transmitted to
      vertebrates by Ixodes ticks. The classical and alternative complement pathways
      are important in Borrelia eradication by the vertebrate host. We recently
      identified a tick salivary protein, designated P8, which reduced complement
      mediated killing of Borrelia. We now discover that P8 interferes with the human
      lectin complement cascade, resulting in impaired neutrophil phagocytosis and
      chemotaxis and diminished Borrelia lysis. Therefore, P8 was renamed the tick
      salivary lectin pathway inhibitor (TSLPI). TSLPI-silenced ticks, or ticks exposed
      to TSLPI-immune mice, were hampered in Borrelia transmission. Moreover, Borrelia
      acquisition and persistence in tick midguts was impaired in ticks feeding on
      TSLPI-immunized, B. burgdorferi-infected mice. Together, our findings suggest an
      essential role for the lectin complement cascade in Borrelia eradication and
      demonstrate how a vector-borne pathogen co-opts a vector protein to facilitate
      early mammalian infection and vector colonization.

PMID- 21843871
TI  - The Hypervariable region of Streptococcus pyogenes M protein escapes antibody
      attack by antigenic variation and weak immunogenicity.
AB  - Sequence variation of antigenic proteins allows pathogens to evade antibody
      attack. The variable protein commonly includes a hypervariable region (HVR),
      which represents a key target for antibodies and is therefore predicted to be
      immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed
      the clinically important HVR-containing M proteins of the human pathogen
      Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost
      exclusively against the C-terminal part and not against the N-terminal HVR.
      Similar results were obtained for mice and humans with invasive S. pyogenes
      infection. Nevertheless, only anti-HVR antibodies protected efficiently against
      infection, as shown by passive immunizations. The HVR fused to an unrelated
      protein elicited no antibodies, implying that it is inherently weakly
      immunogenic. These data indicate that the M protein HVR evades antibody attack
      not only through antigenic variation but also by weak immunogenicity, a
      paradoxical observation that may apply to other HVR-containing proteins.

PMID- 21843872
TI  - Nutrient metal sequestration by calprotectin inhibits bacterial superoxide
      defense, enhancing neutrophil killing of Staphylococcus aureus.
AB  - By sequestering manganese and zinc, the neutrophil protein calprotectin plays a
      crucial role in host defense against bacterial and fungal pathogens. However, the
      essential processes disrupted by calprotectin remain unknown. We report that
      calprotectin enhances the sensitivity of Staphylococcus aureus to superoxide
      through inhibition of manganese-dependent bacterial superoxide defenses, thereby
      increasing superoxide levels within the bacterial cell. Superoxide dismutase
      activity is required for full virulence in a systemic model of S. aureus
      infection, and disruption of staphylococcal superoxide defenses by calprotectin
      augments the antimicrobial activity of neutrophils promoting in vivo clearance.
      Calprotectin mutated in two transition metal binding sites and therefore
      defective in binding manganese and zinc does not inhibit microbial growth,
      unequivocally linking the antimicrobial properties of calprotectin to metal
      chelation. These results suggest that calprotectin contributes to host defense by
      rendering bacterial pathogens more sensitive to host immune effectors and
      reducing bacterial growth.

PMID- 21843873
TI  - RNA-Seq-based monitoring of infection-linked changes in Vibrio cholerae gene
      expression.
AB  - Pathogens adapt to the host environment by altering their patterns of gene
      expression. Microarray-based and genetic techniques used to characterize
      bacterial gene expression during infection are limited in their ability to
      comprehensively and simultaneously monitor genome-wide transcription. We used
      massively parallel cDNA sequencing (RNA-seq) techniques to quantitatively catalog
      the transcriptome of the cholera pathogen, Vibrio cholerae, derived from two
      animal models of infection. Transcripts elevated in infected rabbits and mice
      relative to laboratory media derive from the major known V. cholerae virulence
      factors and also from genes and small RNAs not previously linked to virulence.
      The RNA-seq data was coupled with metabolite analysis of cecal fluid from
      infected rabbits to yield insights into the host environment encountered by the
      pathogen and the mechanisms controlling pathogen gene expression. RNA-seq-based
      transcriptome analysis of pathogens during infection produces a robust,
      sensitive, and accessible data set for evaluation of regulatory responses driving
      pathogenesis.

PMID- 21843874
TI  - Improved assessment of control in intermittent exotropia using multiple measures.
AB  - PURPOSE: To develop and validate an improved measure of control in intermittent
      exotropia (XT). DESIGN: Prospective, noninterventional case series. METHODS:
      Twelve children with intermittent XT were evaluated during 4 sessions (2 hours
      apart) over a day, on 2 separate days (8 sessions per child). Control was
      standardized using a scoring system and quantified 3 times during each
      examination. Overall control for a day was calculated as the mean of all 12
      measures. Single measures of control and the mean of 2 (double) and 3 (triple)
      measures over the examination were compared with the respective day mean, and
      first-day measures were compared to the second-day mean. RESULTS: At distance,
      17% (49/287, 95% confidence interval [CI] 13% to 22%) of single measures differed
      from the day mean, whereas only 8% (16/191, 95 CI 5% to 13%) of double measures
      and 5% (5/95, 95% CI 2% to 12%) of triple measures differed. Comparing day 1
      measures to overall mean for day 2, 17% (24/143, 95% CI 11% to 24%) of single
      measures and 17% (22/130, 95% CI 11% to 24%) of double measures differed by more
      than 1 level, whereas 11% (5/47, 95% CI 4% to 23%) of triple measures differed.
      CONCLUSIONS: The mean of 3 assessments of control during a clinic examination
      better represents overall control than a single measure.

PMID- 21843875
TI  - Medicare costs for neovascular age-related macular degeneration, 1994-2007.
AB  - PURPOSE: To assess changes in Medicare payments for neovascular age-related
      macular degeneration (AMD) since introduction of anti-vascular endothelial growth
      factor (VEGF) therapies. DESIGN: Retrospective, longitudinal cohort study.
      METHODS: Using the Medicare 5% sample, beneficiaries with new diagnoses of
      neovascular AMD in 1994 (N = 2497), 2000 (N = 3927), and 2006 (N = 6041) were
      identified using International Classification of Diseases (ICD-9-CM). The total
      first-year health care and eye care costs were calculated for each beneficiary.
      Propensity score matching was used to match individuals in the 2000 and 2006
      cohorts with the 1994 cohort on age, sex, race, Charlson Comorbidity Index, and
      low vision/blindness. RESULTS: The number of beneficiaries newly diagnosed with
      neovascular AMD more than doubled between the 1994 and 2006 cohorts. Overall
      yearly Part B payments per beneficiary increased significantly from $3567 for the
      1994 to $5991 for the 2006 cohort (P < .01) in constant 2008 dollars. Payments
      for eye care alone doubled from $1504 for the 1994 cohort to $3263 for the 2006
      cohort (P < .01). Most of the increase in payments for eye care in 2006 reflected
      payments for anti-VEGF injections, which were $1609 over 1 year. Mean annual
      numbers of visits and imaging studies also increased significantly between the
      1994 and 2006 cohort. Results were similar in the matched sample. CONCLUSIONS:
      The introduction of anti-VEGF intravitreal injections has offered remarkable
      clinical benefits for patients with neovascular AMD, but these benefits have come
      at the cost of an increased financial burden of providing care for these
      patients.

PMID- 21843877
TI  - Management of rhegmatogenous retinal detachment with coexistent macular hole in
      the era of internal limiting membrane peeling.
AB  - PURPOSE: To review outcomes of vitrectomy plus or minus scleral buckling for
      retinal detachment (RD) attributable to peripheral break(s) with noncausal
      macular hole, plus or minus internal limiting membrane (ILM) peeling. DESIGN:
      Retrospective chart review. METHODS: Forty-nine consecutive patients from March
      1, 1998 to March 31, 2009 with RD attributable to peripheral break and macular
      hole were treated by vitrectomy. Five had no scleral buckle placed. Forty-three
      underwent ILM peeling. RESULTS: The main outcome measures were retinal
      reattachment, macular hole status, and vision. Final retinal reattachment rate
      was 95.9% (47/49) with 1 and 100% with 2 operations. Final macular hole closure
      rate was 39/43 with ILM peeling (90.7%), and 2/6 without (33.3%, P value =
      .0041). Mean final acuity was 20/120, and 20/100 if the macular hole was closed.
      CONCLUSION: Vitrectomy, plus or minus scleral buckle, with ILM peeling is
      effective for repair of RD with macular hole. ILM peeling can increase the rate
      of macular hole closure.

PMID- 21843876
TI  - Effects of argon laser trabeculoplasty in the Early Manifest Glaucoma Trial.
AB  - PURPOSE: To analyze reduction of intraocular pressure (IOP) by argon laser
      trabeculoplasty (ALT) in the Early Manifest Glaucoma Trial and factors
      influencing the effect of such treatment. DESIGN: Cohort study based on 127
      patients from the treatment group of the Early Manifest Glaucoma Trial, a
      randomized clinical trial. METHODS: Patients randomized to the treatment arm of
      the Early Manifest Glaucoma Trial received a standard treatment protocol (topical
      betaxolol hydrochloride followed by 360-degree ALT) and then were followed up
      prospectively at 3-month intervals for up to 8 years. One eye per patient was
      included in the analyses. We investigated the relationship between IOP before ALT
      and subsequent IOP reduction and other factors that might have influenced the
      effect of ALT, including stage of the disease, trabecular pigmentation, presence
      of exfoliation syndrome, and treating surgeon. RESULTS: The mean +/- standard
      deviation IOP before ALT and after betaxolol treatment was 18.1 +/- 3.9 mm Hg,
      and the mean +/- standard deviation short-term IOP reduction 3 months after ALT
      was 2.8 +/- 3.9 mm Hg (12.6 +/- 20.5%). The IOP before ALT strongly affected IOP
      reduction (P < .001); each 3-mm Hg higher IOP before ALT value was associated
      with an additional mean IOP reduction of approximately 2 mm Hg. The treating
      surgeons also had a significant impact on IOP reduction (P = 0.001), with mean
      values ranging from 5.8 to -1.3 mm Hg. CONCLUSIONS: In this cohort, which
      included many patients with low IOP levels, IOP before ALT markedly influenced
      the IOP reduction induced by ALT, seen as a much larger decrease in eyes with
      higher IOP before ALT. The treating surgeon also had a significant impact on ALT
      outcome.

PMID- 21843878
TI  - At similar angles, slope walking has a greater fall risk than stair walking.
AB  - According to the CDC, falls are the leading cause of injury for all age groups
      with over half of the falls occurring during slope and stair walking.
      Consequently, the purpose of this study was to compare and contrast the different
      factors related to fall risk as they apply to these walking tasks. More
      specifically, we hypothesized that compared to level walking, slope and stair
      walking would have greater speed standard deviation, greater ankle dorsiflexion,
      and earlier peak activity of the tibialis anterior. Twelve healthy, young male
      participants completed level, slope, and stair trials on a 25-m walkway. Overall,
      during slope and stair walking, medial-lateral stability was less, anterior
      posterior stability was less, and toe clearance was greater in comparison to
      level walking. In addition, there were fewer differences between level and stair
      walking than there were between level and slope walking, suggesting that at
      similar angles, slope walking has a greater fall risk than stair walking.

PMID- 21843879
TI  - Advantages of shift changeovers with meetings: ergonomic analysis of shift
      supervisors' activity in aircraft building.
AB  - Good shift changeovers contribute to ensuring continuity and reliability in shift
      work. In situations where production is not maintained 24 h a day, changeovers
      with meetings (SCM) between the two work teams (written plus oral face-to-face
      handovers) alternate with changeovers without meetings (SCnM; written handovers
      only). An ergonomic work analysis on an aircraft assembly line showed that (1)
      incoming and outgoing operators met during the overlap time allotted by the
      company, and (2) the content of the exchanges was richer for SCMs than for SCnMs.
      SCMs enabled the operators to pass on and process more aspects of their work than
      SCnMs did. SCMs also allowed incoming operators to validate their predictions,
      and enabled both outgoing and incoming operators to update their mental models
      and work together on peripheral aspects of the technical process over a greater
      time span. The findings highlight the importance of allowing overlap time in
      shift work.

PMID- 21843880
TI  - Synthesis and evaluation of an N-acetylglucosamine biosynthesis inhibitor.
AB  - The structural rationale, synthesis and evaluation of an inhibitor designed to
      block glucosamine synthesis by competitively inhibiting the action of glutamine:
      fructose-6-phosphate amidotransferase and subsequently reducing the
      transformation of any glucosamine-6-phosphate formed to UDP-N-acetylglucosamine
      are described. The inhibitor 2-acetamido-2,6-dideoxy-6-sulfo-D-glucose (D
      glucosamine-6-sulfonate) is an analog of glucosamine-6-phosphate in which the
      phosphate group in the latter is replaced with a sulfonic acid group. The
      inhibitor is designed to function by three different modes which together reduce
      UDP-N-acetylglucosamine synthesis. This reduction was confirmed by evaluating the
      effect of the inhibitor on bacterial cell-wall synthesis and by demonstrating
      that it inhibits acetylation of glucosamine-6-phosphate competitively and by
      acting as a surrogate substrate. Inhibition of glucosamine production or suitably
      activated glucosamine in bacteria leads to disruption of the peptidoglycan
      structure, which results in softening, bulging, deformation, fragility and lysis
      of the cells. These modifications were documented by scanning electron microscopy
      for bacteria treated with the inhibitor. They were observed for inhibitor
      concentrations in the 20 mg/mL range for Escherichia coli and Bacillus subtilis
      and the 5 mg/mL range for Rhizobium trifolii.

PMID- 21843881
TI  - Imaging of lytic granule exocytosis in CD8+ cytotoxic T lymphocytes reveals a
      modified form of full fusion.
AB  - Here we imaged the exocytosis of lytic granules from human CD8(+) cytotoxic T
      lymphocytes using rapid total internal reflection microscopy, Lamp-1 tagged with
      mGFP to follow the fate of the lytic granule membrane, and granzyme A, granzyme B
      or serglycin tagged with mRFP to follow the fate of lytic granule cargo. Lytic
      granules were released by full fusion with the plasma membrane, such that the
      entire granule content for all three cargos visualized was released on a
      subsecond time scale. The behavior of GFP-Lamp-1 was, however, more complex.
      While it entered the plasma membrane in all cases, the extent to which it then
      diffused away from the site of exocytosis varied from nearly complete to highly
      restricted. Finally, the diffusion properties upon release of the three cargos
      examined put an upper limit on the size of the macromolecular complex of granzyme
      and serglycin that is presented to the target cell.

PMID- 21843882
TI  - Is dual-phase abdominal CT necessary for the optimal detection of metastases from
      renal cell carcinoma?
AB  - AIM: To determine whether dual-phase abdominal computed tomography (CT) detected
      more metastases than portal-phase CT alone in patients with renal cell carcinoma
      (RCC). MATERIALS AND METHODS: Audit committee approval was obtained. A
      retrospective audit was undertaken in 100 patients who underwent both arterial
      and portal phase CT. The CT images were independently reviewed by two consultant
      radiologists. The presence of metastases in the liver, pancreas, and
      contralateral kidney were recorded for each phase of contrast enhancement.
      RESULTS: Metastases were identified in the liver in 27 patients, pancreas in 12,
      and contralateral kidney in 23 patients. Nine of the 27 (33%) liver metastases,
      three of the 12 (25%) pancreatic metastases, and two of the 23 (9%) renal
      metastases were only detected in the arterial phase, whilst four of the 27 (15%)
      liver metastases, three of the 12 (25%) pancreatic metastases, and two of the 23
      (9%) renal metastases were only detected in the portal phase. Nine patients (9%)
      had metastases only visualized in the arterial phase, and six (6%) only in the
      portal phase. Detection of metastases only visible in the arterial phase led to a
      change of management in two patients (2%). CONCLUSION: The audit results support
      our current standard of dual-phase abdominal CT for optimal detection of RCC
      metastases.

PMID- 21843883
TI  - Male more than female infants imitate propulsive motion.
AB  - Few experimental studies investigate the mechanisms by which young children
      develop sex-typed activity preferences. Gender self-labeling followed by
      selective imitation of same-sex models currently is considered a primary
      socialization mechanism. Research with prenatally androgenized girls and non
      human primates also suggests an innate male preference for activities that
      involve propulsive movement. Here we show that before children can label
      themselves by gender, 6- to 9-month-old male infants are more likely than female
      infants to imitate propulsive movements. Further, male infants' increase in
      propulsive movement was linearly related to proportion of time viewing a male
      model's propulsive movements. We propose that male sex-typed behavior develops
      from socialization mechanisms that build on a male predisposition to imitate
      propulsive motion.

PMID- 21843884
TI  - Single-case research in neuropsychology: a comparison of five forms of t-test for
      comparing a case to controls.
AB  - Five inferential methods employed in single-case studies to compare a case to
      controls are examined; all of these make use of a t-distribution. It is shown
      that three of these ostensibly different methods are in fact strictly equivalent
      and are not fit for purpose; they are associated with grossly inflated Type I
      errors (these exceed even the error rate obtained when a case's score is
      converted to a z score and the latter used as a test statistic). When used as
      significance tests, the two remaining methods (Crawford and Howell's method and a
      prediction interval method first used by Barton and colleagues) are also
      equivalent and achieve control of the Type I error rate (the two methods do
      differ however in other important aspects). A number of broader issues also arise
      from the present findings, namely: (a) they underline the value of accompanying
      significance test results with the effect size for the difference between a case
      and controls, (b) they suggest that less care is often taken over statistical
      methods than over other aspects of single-case studies, and (c) they indicate
      that some neuropsychologists have a distorted conception of the nature of
      hypothesis testing in single-case research (it is argued that this may stem from
      a failure to distinguish between group studies and single-case studies).

PMID- 21843885
TI  - Infertility reversed by glucocorticoids and full-term pregnancy in a couple with
      previously undiagnosed nonclassic congenital adrenal hyperplasia.
AB  - OBJECTIVE: To report the case of a couple with infertility and two unsuccessful
      previous attempts of ovarian stimulation for in vitro fertilization (IVF), whose
      nonclassic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase
      deficiency (21-OHD) was diagnosed and verified by molecular studies. DESIGN: Case
      report. SETTING: Outpatient practice and academic hospital. PATIENT(S): A woman
      with hyperandrogenism, luteal phase deficiency, and polycystic ovaries, and a man
      with oligospermia, a high rate of abnormal forms of spermatozoa (>95%), decreased
      sperm motility, and normal testicular volume. INTERVENTION(S): Ultrasonography,
      semen analysis, endocrinologic assays, corticosteroids. MAIN OUTCOME MEASURE(S):
      Increased basal and adrenocorticotropic hormone (ACTH) stimulated 17alpha
      hydroxyprogesterone (17-OHP) values were detected in both partners. CYP21A2
      genotyping revealed compound heterozygosity in both wife and husband (wife:
      p.P30L/p.P453S; husband: p.P453S /p.V281L). RESULT(S): Hydrocortisone, 30 mg/day
      orally, was administered to both wife and husband. Forty days later, a pregnancy
      was detected. The prospective mother continued to receive hydrocortisone (25
      mg/day) adjusted according to her hormone status. After a full-term uneventful
      pregnancy, a completely normal female was born. The baby had NC-CAH (genotype
      p.P30L/p.V281L). CONCLUSION(S): Nonclassic congenital adrenal hyperplasia, a
      potential cause of infertility in couples, can be successfully treated with
      corticosteroids.

PMID- 21843886
TI  - Assisted reproduction services provision in a developing country: time to act?
AB  - OBJECTIVE: To conduct a survey in a developing country to gauge the extent of
      subfertility and the current state of assisted reproductive technology (ART)
      service provision and explore factors limiting access to ART services. DESIGN:
      Cross-sectional online survey. SETTING: The study was co-ordinated at the Aga
      Khan University Hospital, Nairobi, Kenya. SUBJECT(S): One hundred eighty-eight
      obstetricians and gynecologists registered with the Kenya Obstetrics and
      Gynecology Society were invited to complete the survey. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): None. RESULT(S): A total of 47 responses (25%) were
      received after completion of the survey. The overall rate of subfertility was
      26.1% among the gynecology consultations, with 50% attributed to tubal factors
      and 15% due to male factors. Assisted reproductive service provision
      (IVF/intracytoplasmic sperm injection) was severely limited to only three units,
      despite the reported high rate of tubal disease. The high cost of treatment,
      patients' limited finances, and limited local services were almost universally
      cited as the main barriers to ART services in Kenya. CONCLUSION(S): The demand
      for ART in developing countries is not in doubt. Simplified, less costly, and
      more accessible ART approaches need to be considered in developing countries,
      even though the benefits and outcomes of such approaches may not be apparent
      immediately.

PMID- 21843887
TI  - Fertility clinic, egg donation agency, and sperm bank policies.
AB  - OBJECTIVE: To assess the level of openness in U.S. gamete donation policies
      across fertility clinics, egg donation agencies, and sperm banks. DESIGN:
      Primarily a content analysis of organizational materials (e.g., websites,
      brochures). SETTING: Not applicable. PARTICIPANT(S): A total of 219 fertility
      clinics, 100 egg donation agencies, and 30 sperm banks. INTERVENTION(S): Not
      applicable. MAIN OUTCOME MEASURE(S): Use of donor photographs, anonymity between
      parties, cycle outcome disclosure, and postcycle contact. RESULT(S): Agencies
      were more likely to provide donor photographs, have proactive policies to inform
      donors of the cycle outcome, and have nonanonymous options compared with sperm
      banks and clinics. Sperm banks were more likely to offer institutionalized donor
      identity-release programs. CONCLUSION(S): Clinics, agencies, and sperm banks have
      different policies to address the level of openness between donors, recipients,
      and donor-conceived children. Although agencies generally offer more open
      arrangements, only a minority of organizations restricted all types of contact
      and communication between parties.

PMID- 21843888
TI  - High exposure to progesterone between the end of menstruation and the day of
      triggering final oocyte maturation is associated with a decreased probability of
      pregnancy in patients treated by in vitro fertilization and intracytoplasmic
      sperm injection.
AB  - OBJECTIVE: To investigate the association between the probability of pregnancy
      and hormone exposure between the end of menstruation and the day of triggering
      final oocyte maturation (menstruation-free interval). DESIGN: Prospective study.
      SETTING: University. PATIENT(S): One hundred women (aged <= 39 years) stimulated
      with a fixed dose of recombinant follicle-stimulating hormone (200 IU).
      INTERVENTION(S): Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg)
      used from day 6 of stimulation onward, final oocyte maturation triggered by
      administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as >= 3
      follicles >= 17 mm were present, and hormone assessment performed at initiation
      of stimulation, on the first day after menstruation had stopped, on the day of
      antagonist initiation, and on the day of hCG administration. MAIN OUTCOME
      MEASURE(S): The association between hormone exposure during the menstruation-free
      interval and the probability of ongoing pregnancy. RESULT(S): The exposure to
      progesterone during the menstruation-free interval was statistically
      significantly higher in patients who did not become pregnant compared with those
      who did (4.20 +/- 2.54 vs. 3.13 +/- 1.14, respectively). Binary logistic
      regression confirmed the adverse effect of the increased exposure to progesterone
      for the achievement of pregnancy. CONCLUSION(S): In recombinant follicle
      stimulating hormone/gonadotropin-releasing hormone antagonist in vitro
      fertilization/intracytoplasmic sperm injection cycles, a lower probability of
      pregnancy is associated with a higher exposure to progesterone during the
      menstruation-free interval.

PMID- 21843889
TI  - Combined oral contraceptives in women with menstrual migraine without aura.
AB  - OBJECTIVE: To compare the efficacy of two regimens (21 active pills + 7 placebo
      pills vs. 24 active pills + 4 placebo pills) of combined oral contraception
      (COC), both containing 20 MUg of ethinyl E(2) and 3 mg of drospirenone, in
      improving the severity of pure menstrual migraine without aura. DESIGN:
      Prospective randomized study. SETTING: Patients attending the gynecology
      department of the University of Siena for consultation regarding an appropriate
      contraception. PATIENT(S): Women ages 20 to 35 years (n = 60) suffering from pure
      menstrual migraine without aura. INTERVENTION(S): Three months of contraceptive
      use (ethinyl E(2) 20 MUg/drospirenone 3 mg) in two different regimens: group A
      received 21 active + 7 placebo pills whereas group B received 24 active + 4
      placebo pills. MAIN OUTCOME MEASURE(S): Monthly evaluation of the duration and
      severity of patients' daily headache attacks. RESULT(S): Although both study
      groups demonstrated significant reduction in the intensity and duration of
      menstrual migraine, patients in group B (24/4 COC) reported a significant
      reduction in the intensity and a shorter duration of their menstrual migraine,
      compared with group A (21/7 COC). CONCLUSION(S): The 24/4 COC regimen is
      recommended as the preferred treatment for patients suffering from pure menstrual
      migraine without aura.

PMID- 21843890
TI  - Comparisons of inhibin B versus antimullerian hormone in poor ovarian responders
      undergoing in vitro fertilization.
AB  - OBJECTIVE: To evaluate serum inhibin B as a predictor of poor ovarian response in
      patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF
      ICSI) and to compare it with the performance of antimullerian hormone (AMH).
      DESIGN: Meta-analysis. SETTING: University hospital. PATIENT(S): Patients
      undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Poor ovarian
      response in controlled ovarian hyperstimulation (COH). RESULT(S): Fifteen studies
      on serum inhibin B and 12 studies on AMH were selected for meta-analysis. Both
      basal and stimulated inhibin B levels were statistically significantly lower in
      poor ovarian responders than in controls. The estimated summary receiver
      operating characteristic (ROC) curves suggested that stimulated inhibin B was
      more accurate than basal inhibin B and AMH in the prediction of poor ovarian
      response. CONCLUSION(S): Both basal and stimulated serum inhibin B levels are
      lower in poor responders than in controls. Compared with AMH, stimulated inhibin
      B is a more accurate predictor of ovarian response in patients undergoing IVF,
      making it a potentially useful tool in future IVF practice.

PMID- 21843891
TI  - Analysis of interfacial and micellar behavior of sodium dioctyl sulphosuccinate
      salt (AOT) with zwitterionic surfactants in aqueous media.
AB  - The interfacial and bulk properties of mixtures of the anionic surfactant
      (dioctyl sulphosuccinate sodium salt, AOT) with zwitterionic surfactants 3-(N,N
      dimethyldodecylammonio) propane sulfonate (DPS), 3-(N,N
      dimethyltetradecylammonio) propane sulfonate (TPS), 3-(N,N
      dimethylhexadecylammonio) propane sulfonate (HPS) have been studied employing
      surface tension, fluorescence, and viscometric techniques in aqueous media at 25 
      degrees C. It is observed that these mixtures exhibit synergism and these
      synergistic interactions increase with the enhancement of the hydrocarbon chain
      of the zwitterionic surfactant. The various physicochemical properties such as
      critical micelle concentration (cmc), surface excess concentration (G(max)),
      minimum area per molecule (A(min)), aggregation number (N(agg)), interaction
      parameters (beta(sigma), beta(m)), and thermodynamic parameters such as standard
      Gibbs free energy of adsorption (DeltaG(ads)(o)), excess free energy of
      micellization (DeltaG(ex)), and standard Gibbs free energy of micellization
      (DeltaG(m)(o)) have been evaluated. The negative values of DeltaG(m)(o) and
      DeltaG(ads)(o) show that the micelle formation and adsorption of surfactant at
      the air/solution interface is energetically favorable, while a negative value of
      DeltaG(ex) ensures stability of the mixed micelles formed. The Regular Solution
      Approximation, Motomura and Rosen's approaches have been used to explain and
      compare the results. The packing parameter (p) ensures the formation of vesicles
      or bilayers for AOT+DPS/TPS mixtures, which can potentially be used as delivery
      agents for industrial applications.

PMID- 21843892
TI  - Adsorption of paraquat on mesoporous silica modified with titania: effects of pH,
      ionic strength and temperature.
AB  - The adsorption of the herbicide paraquat (PQ(2+)) on the binary system titania
      silica has been studied in batch experiments by performing adsorption isotherms
      under different conditions of pH, supporting electrolyte concentration, and
      temperature. Adsorption kinetic on the studied material has also been carried out
      and discussed. PQ(2+) adsorption is very low on the bare silica surface but
      important on the composed TiO(2)-SiO(2) adsorbent. In this last case, the
      adsorption increases by increasing pH and decreasing electrolyte concentration.
      There are no significant effects of temperature on the adsorption. The increase
      of the adsorption in TiO(2)-SiO(2) seems to be related to an increase in acid
      sites of the supported titania and to the homogenously dispersion of the TiO(2)
      nanoparticles over the silica support. The adsorption takes place by direct
      binding of PQ(2+) to TiO(2) leading to the formation of surface species of the
      type SiO(2)-TiO(2)-PQ(2+). Electrostatic interactions and charge-transfer and
      outer-sphere complexes formations seem to play a key role in the adsorption
      mechanism. The analysis of thermodynamic parameters suggests that the adsorption
      on TiO(2)-SiO(2) is endothermic and spontaneous in nature.

PMID- 21843893
TI  - On-pump and off-pump coronary artery bypass grafting in patients with left main
      stem disease: a propensity score analysis.
AB  - OBJECTIVE: This study compared safety and efficacy between off-pump coronary
      artery bypass grafting (OPCAB), a relatively new technique, and conventional on
      pump coronary artery bypass grafting (CCAB) in patients with left main stem
      disease. METHODS: In a retrospective, observational, cohort study of
      prospectively collected data on 2375 consecutive patients with left main stem
      disease undergoing isolated CABG (1297 OPCAB, 1078 CCAB) between April 1996 and
      December 2009 at the Bristol Heart Institute, 548 patients undergoing OPCAB were
      matched with 548 patients undergoing CCAB by propensity score. RESULTS: After
      propensity matching, groups were comparable in preoperative characteristics.
      Relative to CCAB, OPCAB was associated with lower in-hospital mortality (0.5% vs
      2.9%; P = .001), incidence of stroke (0% vs 0.9%; P = .02), postoperative renal
      dysfunction (4.9% vs 10.8%; P = .001), pulmonary complications (10.2% vs 16.6%; P
      = .002), and infectious complications (3.5% vs 6.2%; P = .03). The OPCAB group
      received fewer grafts than did the CCAB group (2.7 +/- 0.7 vs 3 +/- 0.7; P =
      .001) and had a lower rate of complete revascularization (88.3% vs 92%; P = .04).
      In multivariable analysis, cardiopulmonary bypass was confirmed to be an
      independent predictor of in-hospital mortality (odds ratio, 5.74; P = .001).
      Survivals at 1, 5, and 10 years were similar between groups (OPCAB, 96.8%, 87.3%,
      and 71.7%; CCAB, 96.8%, 88.6%, and 69.8%). CONCLUSIONS: OPCAB in patients with
      left main stem disease is a safe procedure with reduced early morbidity and
      mortality and similar long-term survival to conventional on-pump
      revascularization.

PMID- 21843894
TI  - In vitro protection of vascular function from oxidative stress and inflammation
      by pulsatility in resistance arteries.
AB  - OBJECTIVE: Resistance arteries remain subject to pulsatility, a potent regulator
      of large elastic artery tone and structure, but the effect is incompletely
      understood. Extracorporeal circulation during cardiac surgery is often associated
      with absence of pulsatility, which may affect vascular tone. To define the role
      of the vascular wall in the inflammatory process that may occur with or without
      pulsatility, we studied resistance arteries functions ex vivo. We measured
      vascular reactivity, oxidative stress, and inflammation in the arterial wall.
      METHODS: Isolated rat mesenteric resistance arteries were mounted in an
      arteriograph and subjected to pulsatility or not in vitro. Arteries were perfused
      with a physiologic salt solution without circulating cells. RESULTS: After 180
      minutes, flow-mediated dilation was higher and pressure-induced myogenic tone
      lower in arteries subjected to pulsatility. Without pulsatility, reactive oxygen
      species and markers of inflammation (monocyte chemotactic protein 1 and tumor
      necrosis factor alpha) were higher than baseline. In perfused mesenteric beds
      under similar conditions, tumor necrosis factor alpha was higher in perfusate
      after 180 minutes of nonpulsatility (5.7 +/- 1.6 pg/mL vs 1.1 +/- 0.4 pg/mL; P <
      .01). In arteries treated with the antioxidant 4-hydroxy-2,2,6,6
      tetramethylpiperidin-1-oxyl (tempol), flow-mediated dilation and myogenic tone
      were similar in nonpulsatile and pulsatile arteries; monocyte chemotactic protein
      1 and nuclear factor kappaB expression levels were not increased in tempol
      treated nonpulsatile arteries. CONCLUSIONS: Absence of pulsatility in resistance
      arteries increased oxidative stress, which in turn induced inflammation and
      preferentially altered pressure and flow-dependent tone, which play a key role in
      control of local blood flow.

PMID- 21843896
TI  - Structural revision of periplocosides and periperoxides, natural
      immunosuppressive agents from the genus Periploca.
AB  - The structures of a series of peroxy function containing pregnane glycosides
      isolated from Periploca sepium and Periploca forrestii were revised to be
      orthoester group bearing ones using 2D NMR spectroscopic techniques, as well as
      chemical transformations and X-ray crystallographic diffraction analysis. The
      orthoester function appears to be an essential structural feature for
      immunosuppressive activity.

PMID- 21843895
TI  - Pitipeptolides C-F, antimycobacterial cyclodepsipeptides from the marine
      cyanobacterium Lyngbya majuscula from Guam.
AB  - Pitipeptolides A (1) and B (2) are cyclic depsipeptides isolated from the marine
      cyanobacterium Lyngbya majuscula from Piti Bomb Holes, Guam. Additional analogues
      have now been isolated by revisiting larger collections of the same
      cyanobacterium. The four identified analogues, pitipeptolides C-F (3-6), are the
      tetrahydro analogue (3), an analogue with a lower degree of methylation (4) as
      well as two homologues (5 and 6) of pitipeptolide A. Their structures were
      elucidated using 2D NMR experiments, chiral HPLC analysis and comparison with
      pitipeptolide A. The identified analogues showed weaker cytotoxic activities
      compared to the two major parent compounds, pitipeptolides A (1) and B (2),
      against HT-29 colon adenocarcinoma and MCF7 breast cancer cells. On the other
      hand, pitipeptolide F (6) was the most potent pitipeptolide in a disc diffusion
      assay against Mycobacterium tuberculosis. The latter finding suggests that the
      structure of pitipeptolides could be optimized for selective antibacterial
      activity.

PMID- 21843897
TI  - In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei.
AB  - During the course of screening to discover antitrypanosomal compounds, 24 known
      plant terpenes (6 sesquiterpenes, 14 sesquiterpene lactones and 4 diterpenes)
      were evaluated for in vitro antitrypanosomal activity against Trypanosoma brucei
      brucei. Among them, 22 terpenes exhibited antitrypanosomal activity. In
      particular, alpha-eudesmol, hinesol, nardosinone and 4-peroxy-1,2,4,5-tetrahydro
      alpha-santonin all exhibited selective and potent antitrypanosomal activities in
      vitro. Detailed here in an in vitro antitrypanosomal properties and
      cytotoxicities of the 24 terpenes compared with two therapeutic antitrypanosomal
      drugs (eflornithine and suramin). This finding represents the first report of
      promising trypanocidal activity of these terpenes. Present results also provide
      some valuable insight with regard to structure-activity relationships and the
      possible mode of action of the compounds.

PMID- 21843898
TI  - Discussion of Arnaldos, M., Pagilla, K., 2010. Effluent dissolved organic
      nitrogen and dissolved phosphorus removal by enhanced coagulation and
      microfiltration. Water Research 44, 5306-5315.

PMID- 21843899
TI  - Occurrence of nine nitrosamines and secondary amines in source water and drinking
      water: Potential of secondary amines as nitrosamine precursors.
AB  - Due to their high carcinogenicity, the control of nitrosamines, a group of
      disinfection by-products (DBPs), is an important issue for drinking water
      supplies. In this study, a method using ultra-performance liquid chromatography
      electrospray ionization tandem mass spectrometry was improved for simultaneously
      analyzing nine nitrosamines in source water and finished water samples of twelve
      drinking water treatment plants (DWTPs) in China. The method detection limits of
      the nine target analytes were 0.2-0.9 ng/L for the source water samples and 0.1
      0.7 ng/L for the finished water samples. Of the nine nitrosamines, six (N
      nitrosodimethylamine (NDMA), nitrosodiethylamine (NDEA), N-nitrosomorpholine
      (NMor), N-nitrosodi-n-butylamine (NDBA), N-nitrosomethylethylamine (NMEA), and N
      nitrosodiphenylamine (NDPhA)) were detected. The total nitrosamine concentrations
      in source water and finished water samples were no detection-42.4 ng/L and no
      detection-26.3 ng/L, respectively, and NDMA (no detection-13.9 ng/L and no
      detection-20.5 ng/L, respectively) and NDEA (no detection-16.3 ng/L and no
      detection-14.0 ng/L, respectively) were the most abundant. Meanwhile, the
      occurrence of nine secondary amines corresponding to the nine nitrosamines was
      also investigated. All of them except for di-n-propylamine were detected in some
      source water and finished water samples, and dimethylamine (no detection-3.9
      MUg/L and no detection-4.0 MUg/L, respectively) and diethylamine (no detection
      2.4 MUg/L and no detection-1.8 MUg/L, respectively) were the most abundant ones.
      Controlled experiments involving chloramination of four secondary amines
      confirmed that dimethylamine, diethylamine, morpholine and di-n-butylamine in
      water can form the corresponding nitrosamines, with diethylamine and morpholine
      showing significantly higher yields than dimethylamine which has already been
      identified as a precursor of NDMA. This study proved that diethylamine,
      morpholine and di-n-butylamine detected in raw water would be one of the
      important the precursors of NDEA, NMOR and NDBA, respectively, in drinking water.

PMID- 21843900
TI  - Carotid artery dissections: thrombosis of the false lumen.
AB  - Carotid artery dissections are the second leading cause of stroke in young
      adults. The hemostatic response to a dissection involves exposure of the
      subendothelium to the intravascular environment. Platelet activation/aggregation
      superimposed by secondary coagulation cascade activity attempts to heal the
      injury. Failure of the hemostatic response to heal the injury may lead to further
      rupture of the intimal and medial layers, which allows for the blood to penetrate
      these layers to create a false lumen. Continued hemorrhaging into the false lumen
      may result in dissection progression or obstruction of blood supply to the true
      lumen and downstream blood vessels. The effects of thrombosis in the true versus
      false lumen may lead to opposite consequences. True lumen clotting may lead to
      ischemic complications of downstream cerebral vasculature, whereas false lumen
      clotting may lead to dissection healing. Current information on clinical outcomes
      and degree of false lumen clotting in a carotid dissection model is limited, and
      most of the available information on this controversial topic has been inferred
      from aortic dissections. Therefore in this report we summarize the present state
      of knowledge of the pathophysiology, detailed hemostatic response to the injury,
      clinical presentation and treatment of carotid dissections. We also emphasize the
      need for future studies to investigate the degree of false lumen clotting on the
      clinical outcomes of carotid dissections.

PMID- 21843901
TI  - Dermoid cyst of the testis with neural tissue in an adult.
AB  - Although some authors question the validity of the diagnosis of dermoid cyst of
      the testis, it does seem to be identical to tumors seen in the ovary and is
      distinct from a mature teratoma of the testis. Previous cases have described
      variants of the "classical" dermoid cyst, including noncutaneous teratomatous
      elements: bone, cartilage, respiratory epithelium, intestinal mucosa. We describe
      a unique case demonstrating a testicular dermoid cyst containing mature neural
      tissue, which has previously not been described in an adult. It has been
      suggested that these tumors are persistent prepubertal teratomas that are known
      to behave in a benign manner.

PMID- 21843902
TI  - Does body mass index "dilute" the predictive property of prostate-specific
      antigen for tumor volume at radical prostatectomy?
AB  - OBJECTIVE: To evaluate the effect of the body mass index (BMI) as it relates to
      the predictive value of the preoperative prostate-specific antigen (PSA) level
      regarding the tumor volume at radical prostatectomy. Stage migration with the
      widespread use of PSA screening is well documented; however, the association
      between the PSA level and tumor volume is less defined. Additionally, the effect
      of obesity on the serum PSA level might cause relative hemodilution and account
      for the decreased predictive ability of the PSA level to determine the tumor
      volume in the modern era. METHODS: We identified 14 293 patients who had
      undergone radical prostatectomy for prostate cancer from 1987 to 2007 and had a
      documented BMI. Using the clinicopathologic variables, we examined the
      relationship among the BMI, preoperative PSA level, and tumor volume at radical
      prostatectomy using multiple linear regression analysis. RESULTS: An elevated BMI
      was associated with an increased pathologic Gleason score (P < .0001), increased
      tumor volume (P < .0001), and increased prostate size (P < .0001). The
      preoperative PSA level correlated significantly with the tumor volume (P <
      .0001). No significant correlation was found between the BMI and preoperative PSA
      level (P = .39). On multivariate analysis, controlling for the BMI, the
      preoperative PSA level remained a significant predictor of the tumor volume (P <
      .0001). The interaction between the preoperative PSA level and BMI in the
      prediction of the tumor volume was not statistically significant (P = .56),
      suggesting that the BMI does not affect the association between the PSA level and
      tumor volume. CONCLUSION: Our results have shown that the predictive ability of
      the PSA level for tumor volume is not affected by the BMI. There does not appear
      to be a need to correct the serum PSA level in relation to the BMI when used in
      preoperative prediction models of the tumor volume.

PMID- 21843903
TI  - A cascade targeting strategy for brain neuroglial cells employing nanoparticles
      modified with angiopep-2 peptide and EGFP-EGF1 protein.
AB  - Targeted drug delivery to selected brain cell types is a crucial step in
      enhancing therapeutic effects while limiting side effects in non-target cells.
      Here we report on the development and evaluation of a new cascade targeting
      delivery system that employs PEG-PCL nanoparticles modified with both an angiopep
      2 peptide and a EGFP-EGF1 protein for precise targeting of brain neuroglial
      cells. Angiopep-2 penetrates the blood-brain barrier and EGFP-EGF1 binds
      neuroglial cells, providing the system with two stages of targeting. In vitro
      studies demonstrated that both bEnd.3 cells and neuroglial cells had a higher
      uptake of angiopep-2 and EGFP-EGF1 conjugated nanoparticles (AENP) as compared to
      unmodified nanoparticles. Ex vivo imaging showed that AENP had higher
      accumulation in the brain over unmodified nanoparticles and EGFP-EGF1 modified
      nanoparticles. Fluorescent in situ hybridization of brain slides demonstrated
      that AENP co-localized with neuroglial cells. Transmission electron microscopy
      further showed that AENP could target and enter neuroglial cells. This newly
      developed cascade targeting delivery system that precisely targets neuroglial
      cells has great potential in the diagnosis and treatment of neuroglial related
      diseases. Replacing EGFP-EGF1 and angiopep-2 with other ligands may extend the
      utility of the system to diagnose and treat organ diseases beyond brain.

PMID- 21843904
TI  - Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the
      treatment of ovarian cancer peritoneal metastasis.
AB  - Peritoneal metastasis is a major cause of morbidity and mortality in ovarian
      cancer. While intraperitoneal chemotherapy and radiotherapy have shown favorable
      clinical results, both are limited by their non-targeted nature. We aimed to
      develop a biologically targeted nanoparticle therapeutic for the treatment of
      ovarian cancer peritoneal metastasis. Folate-targeted nanoparticles encapsulating
      chemotherapy and/or radiotherapy were engineered. Paclitaxel (Ptxl) was used as
      the chemotherapeutic and yittrium-90 ((90)Y) was employed as the therapeutic
      radioisotope. Folate was utilized as the targeting ligand as most ovarian cancers
      overexpress the folate receptor. Nanoparticle characterization studies showed
      monodispersed particles with controlled Ptxl release. Folate targeting ligand
      mediated the uptake of NPs into tumor cells. In vitro efficacy studies
      demonstrated folate-targeted NPs containing chemoradiotherapy was the most
      effective therapeutic compared to folate-targeted NPs containing a single
      therapeutic or any non-targeted NP therapeutics. In vivo efficacy studies using
      an ovarian peritoneal metastasis model showed that folate-targeted NP
      therapeutics were significantly more effective than non-targeted NP therapeutics.
      Among the folate-targeted therapeutics, the NP containing chemoradiotherapy
      appeared to be the most effective. Our results suggest that folate-targeted
      nanoparticles containing chemoradiotherapy have the potential as a treatment for
      ovarian peritoneal metastasis.

PMID- 21843905
TI  - Assessment of carcass contamination with E. coli O157 before and after washing
      with water at abattoirs in Nigeria.
AB  - The study was carried out to assess the level of beef carcass contamination with
      Escherichia coli including O157 strains before and after washing with water.
      Samples of water used for washing carcasses were collected and thirty beef
      carcasses were swabbed within a period of one month in each of three abattoirs
      located in North-Western states of Nigeria. E. coli were enumerated as indicator
      organisms. Using conventional biochemical tests, the isolation rate of E. coli in
      the 120 swab samples collected in each abattoir from external and internal
      surfaces of the carcasses was 58.3% at Kano abattoir, 70.8% at Sokoto abattoir,
      while 76.7% was recorded at Zango abattoir. E. coli counts from external and
      internal surfaces of the carcasses were enumerated as mean log and ranged between
      4.3 Log(10) and 4.6 Log(10) cfu/cm(2) before washing, while the values were 4.6
      Log(10) and 4.9 Log(10) cfu/cm(2) after washing. Data analysis revealed that the
      increase in E. coli counts after washing carcasses with water was statistically
      significant (P<0.05) in all the abattoirs. However, there was no statistically
      significant difference (P>0.05) between the 3 abattoirs in mean log of E. coli
      counts from external surfaces of carcass after washing. E. coli O157 was
      identified from both the water and surfaces of carcasses using Latex
      agglutination kit. A prevalence of 2.8% of E. coli O157 was detected in 360 swab
      samples from 90 beef carcasses examined. E. coli counts from water used in
      washing carcasses were between 22 and 120 cfu/100 ml. Of the 72 water samples,
      3(4.2%) were positive for E. coli O157. In conclusion, there was increased
      contamination of carcasses during processing and water used in washing carcasses
      might have contributed to carcass contamination in all the abattoirs studied due
      to use of non-potable water.

PMID- 21843907
TI  - 6-Substituted imidazo[1,2-a]pyridines: synthesis and biological activity against
      colon cancer cell lines HT-29 and Caco-2.
AB  - A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a
      multicomponent coupling reaction. Most of these compounds were found to exhibit
      excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst
      not showing significant toxicity against white blood cells. Our studies have
      shown that the proteolytic phase of apoptosis was initiated 2 h after treatment
      with these imidazo-[1,2-a]pyridines. The data suggests that the imidazo[1,2
      a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via
      pathway(s) that include the release of cytochrome c from the mitochondria to the
      cytosol and the activation of caspase 3 and caspase 8.

PMID- 21843906
TI  - Altered regulation of tau phosphorylation in a mouse model of down syndrome
      aging.
AB  - Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21) and is
      associated with an increased risk of Alzheimer's disease (AD). Here, using the
      unique transchromosomic Tc1 mouse model of DS we investigate the influence of
      trisomy of Hsa21 on the protein tau, which is hyperphosphorylated in Alzheimer's
      disease. We show that in old, but not young, Tc1 mice increased phosphorylation
      of tau occurs at a site suggested to be targeted by the Hsa21 encoded kinase,
      dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A). We
      show that DYRK1A is upregulated in young and old Tc1 mice, but that young
      trisomic mice may be protected from accumulating aberrantly phosphorylated tau.
      We observe that the key tau kinase, glycogen synthase kinase3-beta (GSK-3beta) is
      aberrantly phosphorylated at an inhibitory site in the aged Tc1 brain which may
      reduce total glycogen synthase kinase3-beta activity. It is possible that a
      similar mechanism may also occur in people with DS.

PMID- 21843908
TI  - Biological evaluation of a novel water soluble sulphur bridged binuclear
      copper(II) thiosemicarbazone complex.
AB  - The reaction of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4(N,N)
      dimethylthiosemicarbazone (HL) with copper(II) nitrate in methanol yielded water
      soluble [{Cu(L)(CH(3)OH)}(2)](NO(3))(2) . H(2)O. Structural analysis revealed
      that the complex consists of centrosymmetric binuclear entities containing square
      pyramidal copper(II) ions bridged through the sulfur atoms. The spectroscopic
      experimental evidences strongly suggested that the ligand and complex could
      interact with calf thymus DNA (CT-DNA) through intercalation. A gel
      electrophoresis assay demonstrated the ability of the complex to cleave the
      pBR322 plasmid DNA. The complex also exhibited a strong binding to bovine serum
      albumin (BSA) over the ligand. Investigations of antioxidative properties showed
      that the complex has strong radical scavenging properties. Further, the cytotoxic
      effect of the complex was examined on HeLa, Hep G2, and HEp-2, which showed that
      the complex exhibited substantial cytotoxic specificity on HeLa over the other
      two.

PMID- 21843909
TI  - Isoeugenol-based novel potent antioxidants: synthesis and reactivity.
AB  - We are attempting to develop the novel phenolic synthetic antioxidants aimed at
      retarding the effects of free radicals and oxidants. The phenolic compounds (7
      12) were synthesized by Friedel-Crafts alkylation of isoeugenol (1) and phenol
      derivatives (2-6) and their structures were determined by spectroscopic methods.
      All the synthesized phenolic compounds (7-12) except 12 are new. Antioxidant and
      radical scavenging activities of synthesized compounds (7-12) were determined by
      using various in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals
      (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS(+)),
      and superoxide anion radicals (O(2)(-)) scavenging, ferric reducing antioxidant
      power (FRAP) and total antioxidant activity by ferric thiocyanate. The
      antioxidant activities of compounds were compared with standard antioxidants such
      as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and trolox as
      positive controls. The results showed that the synthesized compounds, especially
      10 and 11, had better properties than standard antioxidants (BHT, BHA and
      trolox).

PMID- 21843910
TI  - Serum 25-hydroxyvitamin D in early autumn to ensure vitamin D sufficiency in mid
      winter in professional football players.
AB  - BACKGROUND & AIMS: There is growing awareness that vitamin D sufficiency is
      required for overall optimal health. Most experts agree that 25-hydroxyvitamin D
      levels of at least 75 nmol/L, as sufficient vitamin D status. Our aim was to
      investigate the serum 25-hydroxyvitamin D concentration required in mid-October
      to ensure vitamin D sufficiency in early February, and to assess the rate of
      vitamin D insufficiency in both seasons. METHODS: We measured serum 25
      hydroxyvitamin D, parathormone, and other related biochemical parameters, in a
      sample of 28 professional football players homogeneous in factors influencing
      serum 25-hydroxyvitamin D concentration in a sunny area of southern Spain.
      RESULTS: The serum 25-hydroxyvitamin D concentration of 122.7 nmol/L was
      required; 14.3% reached this level. Ninety-three percent had levels >=75 nmol/L
      in mid-October, and 64% had levels <75 nmol/l in early February (chi(2) test, rho
      = 0.001). CONCLUSIONS: Despite the homogeneity in sunlight exposure and vitamin D
      intake few football players reached the level ensuring vitamin D sufficiency in
      mid-winter, and two thirds had vitamin D insufficiency in early February. Given
      our findings, it would be advisable to assess the vitamin D levels in early
      autumn, although additional studies are necessary.

PMID- 21843911
TI  - Living in the "land of no"? Consumer perceptions of healthy lifestyle portrayals
      in direct-to-consumer advertisements of prescription drugs.
AB  - Direct-to-consumer advertising (DTCA) of prescription drugs is the most common
      form of health communication Americans are exposed to. The effects of DTCA on
      prescription requests and utilization are well established, but little is known
      about the effects of advertisements on health behaviors. Many advertisements,
      especially those promoting drugs to prevent or treat cardiovascular disease,
      refer to lifestyle change as a way to improve health. However, no studies have
      examined how consumers interpret these frequently ambiguous messages. We used in
      depth interviews with 45 participants, recruited in Los Angeles, USA between
      April 2007 and July 2008, to explore perceptions of 5 advertisements for drugs
      that prevent or treat cardiovascular disease (Lipitor((r)), Vytorin((r)),
      Zetia((r)), Caduet((r)), Plavix((r))). We found that participants interpreted
      advertising messages within their own life context and identified four
      trajectories for enacting behavior change versus taking prescription drugs:
      Negotiators, Avoiders, Embracers and Jumpstarters. Underlying these four
      typologies were beliefs about whether lifestyle change was something an
      individual could do or was willing to do. Our results also show how an
      advertisement narrative could potentially shift perceptions of causality by
      suggesting that high cholesterol is primarily hereditary, thereby obviating the
      need for lifestyle change. Some participants stated that they would prefer
      lifestyle change to a particular prescription drug, but felt that others would be
      more likely to embrace taking a prescription drug. This "Third Person Effect" may
      be masking participants' intentions by identifying a more socially desirable
      route to therapeutic change. These findings raise questions about how the
      typologies are distributed in the population and how advertising may shift
      consumers' beliefs over time, thereby contributing to new forms of
      medicalization. Effective regulation of DTCA may require expanding scrutiny
      beyond the accuracy of claims about benefits and risks, to also considering the
      broader narratives in which these claims are made.

PMID- 21843912
TI  - Modality differences in timing and temporal memory throughout the lifespan.
AB  - The perception of time is heavily influenced by attention and memory, both of
      which change over the lifespan. In the current study, children (8 yrs), young
      adults (18-25 yrs), and older adults (60-75 yrs) were tested on a duration
      bisection procedure using 3 and 6-s auditory and visual signals as anchor
      durations. During test, participants were exposed to a range of intermediate
      durations, and the task was to indicate whether test durations were closer to the
      "short" or "long" anchor. All groups reproduced the classic finding that "sounds
      are judged longer than lights". This effect was greater for older adults and
      children than for young adults, but for different reasons. Replicating previous
      results, older adults made similar auditory judgments as young adults, but
      underestimated the duration of visual test stimuli. Children showed the opposite
      pattern, with similar visual judgments as young adults but overestimation of
      auditory stimuli. Psychometric functions were analyzed using the Sample Known
      Exactly-Mixed Memory quantitative model of the Scalar Timing Theory of interval
      timing. Results indicate that children show an auditory-specific deficit in
      reference memory for the anchors, rather than a general bias to overestimate time
      and that aged adults show an exaggerated tendency to judge visual stimuli as
      "short" due to a reduction in the availability of controlled attention.

PMID- 21843913
TI  - Human leukocyte antigen-G in cancer: are they clinically relevant?
AB  - The immunotolerant human leukocyte antigen (HLA)-G has direct inhibitory effects
      on natural killer cells (NK), dendritic cells (DC), T cells and can induce
      tolerant regulatory cells. The expression of HLA-G has been correlated with the
      tolerance of the fetus, the acceptance of organ transplants, and the immune
      escape of tumor cells and virus-infected cells. In the context of malignancies,
      aberrant induction of HLA-G expression has been extensively investigated and its
      clinical relevance has been postulated. We here focus on the HLA-G expression in
      malignancies and its relevance to tumor cell immune escaping and disease
      progression.

PMID- 21843915
TI  - A role for maintenance therapy in managing sarcoma.
AB  - Despite the use of recommended chemotherapy regimens, patients with metastatic
      sarcomas have a poor prognosis. To date, the median overall survival for
      metastatic disease remains less than 18 months. First-line treatment of most
      metastatic sarcomas consists of chemotherapy with or without surgical excision of
      residual disease, followed by "watchful waiting" until disease progression or
      recurrence. According to the current treatment paradigm, recommended by United
      States and European clinical guidelines, chemotherapy is administered for a fixed
      number of cycles, and then a watchful waiting approach is taken once a best
      response is achieved. Single-agent doxorubicin remains the standard for treatment
      of most soft-tissue sarcomas (STS), as combination and dose-intense regimens have
      largely failed to improve survival. Combination chemotherapy is the standard
      treatment approach for osteosarcoma and Ewing's sarcoma, but outcomes are poor
      for patients with recurrent disease. In order to improve outcomes (in particular,
      progression-free survival [PFS] and overall survival [OS]), strategies shown to
      be effective in other solid malignancies, such as maintenance therapy and long
      term treatment with targeted therapy, are being investigated in patients with
      advanced sarcomas. One potential promising approach is the use of mammalian
      target of rapamycin (mTOR) inhibitors for maintenance therapy. One such mTOR
      inhibitor, ridaforolimus (AP23573, MK-8669), is currently being evaluated in
      patients with advanced bone and STS in the ongoing Sarcoma mUlti-Center Clinical
      Evaluation of the Efficacy of riDaforolimus (SUCCEED) trial.

PMID- 21843916
TI  - Somatosensory intra-oral activity reveals functional abnormalities in the insula
      of anorexia nervosa suffers.

PMID- 21843914
TI  - Selective targeting of ASIC3 using artificial miRNAs inhibits primary and
      secondary hyperalgesia after muscle inflammation.
AB  - Acid-sensing ion channels (ASICs) are activated by acidic pH and may play a
      significant role in the development of hyperalgesia. Earlier studies show ASIC3
      is important for induction of hyperalgesia after muscle insult using ASIC3-/-
      mice. ASIC3-/- mice lack ASIC3 throughout the body, and the distribution and
      composition of ASICs could be different from wild-type mice. We therefore tested
      whether knockdown of ASIC3 in primary afferents innervating muscle of adult wild
      type mice prevented development of hyperalgesia to muscle inflammation. We cloned
      and characterized artificial miRNAs (miR-ASIC3) directed against mouse ASIC3
      (mASIC3) to downregulate ASIC3 expression in vitro and in vivo. In CHO-K1 cells
      transfected with mASIC3 cDNA in culture, the miR-ASIC3 constructs inhibited
      protein expression of mASIC3 and acidic pH-evoked currents and had no effect on
      protein expression or acidic pH-evoked currents of ASIC1a. When miR-ASIC3 was
      used in vivo, delivered into the muscle of mice using a herpes simplex viral
      vector, both muscle and paw mechanical hyperalgesia were reduced after
      carrageenan-induced muscle inflammation. ASIC3 mRNA in DRG and protein levels in
      muscle were decreased in vivo by miR-ASIC3. In CHO-K1 cells co-transfected with
      ASIC1a and ASIC3, miR-ASIC3 reduced the amplitude of acidic pH-evoked currents,
      suggesting an overall inhibition in the surface expression of heteromeric ASIC3
      containing channels. Our results show, for the first time, that reducing ASIC3 in
      vivo in primary afferent fibers innervating muscle prevents the development of
      inflammatory hyperalgesia in wild-type mice, and thus, may have applications in
      the treatment of musculoskeletal pain in humans.

PMID- 21843917
TI  - Practical use of surimi-like material made from porcine longissimus dorsi muscle
      for the production of low-fat pork patties.
AB  - This study evaluates the effect of replacing fat with surimi-like material (SLM)
      made from the porcine longissimus dorsi muscle on the physicochemical and sensory
      characteristics of pork patties. Pork patties were produced with different levels
      of fat and SLM using a commercial method. Pork patties produced with 20% SLM had
      the lowest fat content (1.76%, P<0.001), and had a higher cooking yield (87.41
      vs. 78.57%, P<0.05) and less shrinkage (4.01 vs. 9.02%, P<0.001) than patties
      produced with 20% back-fat (control). Moreover, patties produced with SLM
      exhibited more acceptable organoleptic characteristics, including tenderness
      (P<0.01) and overall acceptability (P<0.001), than full-fat control patties.
      These results indicated that SLM cannot only be used as a fat replacer, but that
      it also improves the physicochemical and sensory characteristics of low-fat pork
      patties.

PMID- 21843918
TI  - Investigation on the presence of sulphites in fresh meat preparations: estimation
      of an allowable maximum limit.
AB  - Sulphiting agents are commonly used food additives. They are not allowed in fresh
      meat preparations. In this work, 2250 fresh meat samples were analysed to
      establish the maximum concentration of sulphites that can be considered as
      "natural" and therefore be admitted in fresh meat preparations. The analyses were
      carried out by an optimised Monier-Williams Method and the positive samples
      confirmed by ion chromatography. Sulphite concentrations higher than the
      screening method LOQ (10.0 mg . kg(-1)) were found in 100 samples. Concentrations
      higher than 76.6 mg . kg(-1), attributable to sulphiting agent addition, were
      registered in 40 samples. Concentrations lower than 41.3 mg . kg(-1) were
      registered in 60 samples. Taking into account the distribution of sulphite
      concentrations obtained, it is plausible to estimate a maximum allowable limit of
      40.0 mg . kg(-1) (expressed as SO(2)). Below this value the samples can be
      considered as "compliant".

PMID- 21843919
TI  - Factors influencing loco-regional relapse in older breast cancer patients treated
      with tumour resection and tamoxifen.
AB  - BACKGROUND: In breast cancer patients (>=70 years), tumour resection plus
      tamoxifen (T + T) has a higher loco-regional relapse (LR) rate than mastectomy.
      This study examines factors influencing local recurrence in these cases. METHODS:
      Clinical records of 71 patients aged >=70 years, randomised to the T + T arm of 2
      randomised trials were reviewed. Cox Proportional Hazards model was used to
      determine the most significant variables. RESULTS: After 15-years follow-up, LR
      relapse occurred in 29/71, of whom 5 had synchronous metastatic disease. Most
      tumours recurred in the index quadrant. Subsequently 21/24 patients with loco
      regional recurrence only had salvage mastectomy. Three variables significantly
      predicted LR: lympho-vascular invasion (LVI) (HR [95% CI]: 11.18 [4.47, 27.95], p
      < 0.01), ER negative status (HR [95% CI]: 0.27 [0.10, 0.72] p = 0.01), and tumour
      necrosis (HR [95% CI]: 2.65 [1.10, 6.37], p = 0.03). Final margin status was not
      associated with LR. CONCLUSIONS: Tumour resection + Tamoxifen in older patients
      results in long-term local control in the majority with most loco-regional
      failures being salvageable. Risk factors for LR are lympho-vascular invasion, ER
      status and tumour necrosis. Negative tumour excision margins did not
      significantly change local outcome in the absence of radiotherapy. In these older
      patients LVI significantly reduced survival time.

PMID- 21843920
TI  - Mastectomy with immediate breast reconstruction after neoadjuvant chemotherapy
      and radiation therapy. A new option for patients with operable invasive breast
      cancer. Results of a 20 years single institution study.
AB  - PURPOSE: To evaluate the feasability of immediate breast reconstruction (IBR)
      following mastectomy after neoadjuvant chemotherapy (NACT) and radiation therapy
      (RT) for operable invasive breast cancer (OIBC), in terms of incidence of local
      complications, locoregional control and survival. PATIENTS AND METHODS: From 1990
      to 2008, 210 patients were treated by NACT, RT and mastectomy with IBR for OIBC.
      One hundred and seven patients underwent a latissimus dorsi flap with implant
      (LDI), 56 patients a transverse rectus abdominis musculocutaneous (TRAM) flap, 25
      an autologous latissimus dorsi flap (ALD) and 22, a retropectoral implant (RI)
      reconstruction. RESULTS: Forty-six (21.9%) early events were recorded: 20
      necrosis, 9 surgical site infections and 6 haematomas, requiring further surgery
      in 23 patients. More necrosis were observed with TRAM flap reconstructions (p =
      0.000004), requiring more surgical revision than LD reconstructions. Seromas
      represented 42% of early complications in LD reconstructions. Fifty-five patients
      presented with late complications (26.2%) with mainly implant complications
      (capsular contracture, infection, dislocation, deflation) (23.6%), requiring
      reintervention in 14 cases. There were more delayed surgical revisions in RI
      reconstructions (p = 0.0005). The 5 years overall and disease-free survival rates
      were respectively 86.7% and 75.6%. Sixty-four patients presented at least one
      recurrence (30.5%) with 5 local, 9 locoregional and 54 distant relapses.
      CONCLUSION: This therapeutic sequence does not seem to increase the IBR morbidity
      nor alter disease-free and overall survival.

PMID- 21843921
TI  - Surgery following neoadjuvant therapy in patients with HER2-positive locally
      advanced or inflammatory breast cancer participating in the NeOAdjuvant Herceptin
      (NOAH) study.
AB  - AIM: To describe surgical outcomes in patients with HER2-positive locally
      advanced (LABC) or inflammatory breast cancer (IBC) participating in the
      NeOAdjuvant Herceptin (NOAH) study (ISRCTN86043495). PATIENTS AND METHODS: A
      total of 235 patients with HER2-positive disease were randomized to neoadjuvant
      trastuzumab plus chemotherapy (doxorubicin plus paclitaxel, followed by
      paclitaxel, followed by cyclophosphamide, methotrexate and fluorouracil) or
      neoadjuvant chemotherapy alone. Of these patients, 228 received their allocated
      treatment (115 received trastuzumab plus chemotherapy and 113 received
      chemotherapy alone) and were potentially eligible for surgery. Mastectomy was
      required for all patients with IBC and was recommended for all patients with
      LABC. However, breast-conserving therapy could be considered for patients with
      peripheral neoplasms measuring <= 4 cm in diameter at diagnosis, with a favorable
      ratio of tumor to breast volume, or at the patient's request if there had been a
      good response to treatment. RESULTS: As previously reported, the addition of
      trastuzumab to neoadjuvant chemotherapy improved the overall, complete and
      pathological complete response to therapy and significantly improved event-free
      survival (the primary endpoint of the study). Trastuzumab also enabled more
      patients to have breast conserving surgery (BCS) (23% versus 13% respectively)
      without an apparent detrimental effect on local disease control (no patient
      treated with trastuzumab plus chemotherapy had experienced a local recurrence
      after BCS at the time of analysis). CONCLUSIONS: Although this was not an aim of
      the trial, neoadjuvant trastuzumab given concurrently with chemotherapy enabled
      23% of patients with HER2-positive LABC/IBC to avoid mastectomy (including a
      small number of patients with IBC).

PMID- 21843922
TI  - The emerging issue of ratio of metastatic to resected lymph nodes in
      gastrointestinal cancers: an overview of literature.
AB  - The prognosis of gastrointestinal epithelial malignancies is derived from TNM
      staging. The nodal status has the most importance. It guides the subsequent
      adjuvant therapies and gives the oncologist outstanding information about the
      biology of disease. Recently, a growing number of publications seem to be
      attributing importance to a ratio of positive to resected lymph nodes as a bad
      prognostic factor; particularly in gastro-oesophageal carcinomas, colorectal
      carcinomas and also pancreatic cancer. This particular value predicts the best
      significance in optimally (nodal) staged carcinomas, with less accurate, but
      probably equally meaningful information in not adequately resected tumours. Lymph
      node ratio maintains its value even after neo-adjuvant therapy, a factor known to
      be able to reduce lymph nodes' retrieval. The lymph node ratio is most accurate
      when more specialised pathologists in adequate volume cancer centres perform
      treatment and harvest of the lymph nodes. To date, no unconventional radiological
      tool is better able to perform standard armamentarium in correctly defining
      (preoperatively) patient carriers of massive nodal extension. The accurate
      definition of nodal staging is crucial for the potential down-staging benefit of
      neo-adjuvant chemo(radio)therapy on lymph node ratio. In conclusion, lymph node
      ratio stands out as an independent prognostic factor in adequately (nodal)-staged
      gastrointestinal epithelial malignancies and could be useful as a stratification
      factor in future randomised controlled trials.

PMID- 21843923
TI  - Presence of symptoms and timing of surgery do not affect the prognosis of
      patients with primary metastatic breast cancer.
AB  - AIMS: Though most studies on surgical resection of the breast tumor in patients
      with primary distant metastatic breast cancer (MBC) indicated that surgery is
      associated with prolonged overall survival, some state that this effect has been
      confounded by indication and timing of surgery. In this study we analyzed these
      possible confounders and their relation to overall survival. METHODS: To
      determine the impact of potential confounders, individual charts of 279 patients
      with primary MBC were reviewed. RESULTS: The median survival in patients treated
      with surgery of the breast tumor was 39 months, compared to 15 months for those
      without surgery (p < 0.0001). The median survival of patients with symptomatic
      metastatic disease (n = 112) was 19 months, compared to 22 months for those
      without symptomatic disease (n = 167) (p = 0.15). Patients who received surgery
      and whose metastases were detected before surgery of the breast tumor had taken
      place (n = 40) had a median survival of 38 months, compared to 40 months for
      patients in whom the metastatic disease was diagnosed after surgery (n = 43) (p =
      0.81). CONCLUSION: Presence of symptomatic metastatic disease was no significant
      prognostic factor for patients with distant metastasis at diagnosis, neither was
      the timing of surgery. It is unlikely that the prolonged survival after surgery
      is explained by these potentials confounders.

PMID- 21843924
TI  - Clinical commentary in response to: Sensory relearning in peripheral nerve
      disorders of the hand: a web-based survey and Delphi consensus method.

PMID- 21843925
TI  - Memory blocking in schizophrenia reflects deficient retrieval control mechanisms.
AB  - Retrieval interference and orthographic processing were evaluated in
      schizophrenia, schizotypal personality disorder, and non-psychiatric control
      participants using a word fragment completion paradigm. Participants studied
      solutions and later completed corresponding fragments preceded by solutions,
      orthographically similar blocking words, or ampersands. Although schizophrenia
      patients completed fewest fragments, they showed equivalent repetition priming
      and blocking magnitude, supporting intact orthographic processing. Schizophrenia
      patients were more likely to commit intrusions in the blocking condition, whereas
      control participants displayed better mental control because they were more
      likely to withhold the response. These results suggest schizophrenia patients
      show abnormal functioning of control mechanisms responsible for selection and
      inhibition of competitors.

PMID- 21843927
TI  - UK fifth National Colorectal Cancer Consensus Meeting 2010.

PMID- 21843926
TI  - Sensitivity and specificity of the UCSD Performance-based Skills Assessment (UPSA
      B) for identifying functional milestones in schizophrenia.
AB  - Schizophrenia is a highly debilitating illness that often results in disruption
      to independent living and employment. However, "gold standard" methods of
      assessing functional abilities to achieve these milestones are still lacking. In
      a sample of 367 individuals with schizophrenia, we examined the sensitivity and
      specificity of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to
      predict both residential and employment status. Of all individuals residing
      independently, 75.9% scored 78 or above on the UPSA-B, and of all individuals not
      residing independently, 59% scored below 78 on the UPSA-B. Of individuals who
      were employed, 73.9% scored above 82 on the UPSA-B, and of those not employed,
      57.8% scored below 82. These results expand upon both the population base and
      functional milestones with which the UPSA-B is validated, although future work
      should examine whether the UPSA-B can be used as a decision aid in the likelihood
      of success in a longitudinal study, such as at critical transitions (post
      hospitalization, cessation of supported housing).

PMID- 21843928
TI  - Implementation of image-guided brachytherapy for cervix cancer in the UK:
      progress update.
AB  - AIMS: Image-guided brachytherapy (IGBT) is the new gold standard for cervix
      cancer brachytherapy. In 2009, the Royal College of Radiologists (RCR) published
      a guidance document to facilitate the implementation of IGBT for cervix cancer in
      the UK. This paper reports the progress since the publication of the RCR
      document. MATERIALS AND METHODS: Questionnaires were sent to 45 UK centres known
      to offer brachytherapy for cervix cancer in 2011. Replies were received from 43
      (96%) centres. Details collected included brachytherapy machine, imaging
      technique for brachytherapy planning, applicator design and total dose to point A
      from external beam radiotherapy and brachytherapy. The results were compared with
      the 2008 survey reported in the RCR document. RESULTS: The number of centres
      offering computed tomography (CT) or magnetic resonance imaging (MRI)-based IGBT
      for cervix cancer has increased to 32 (71%) in 2011 compared with 12 (26%) in
      2008. Although the most common applicator design in 2011 remains the tandem-ovoid
      applicator (71%), more respondents are using the tandem-ring applicator (29%
      versus 9% in 2008). Only seven (16%) centres are routinely prescribing < 70Gy(10)
      to point A in 2011 compared with 10 (22%) in 2008. CONCLUSION: Considerable
      progress with implementing IGBT for cervix cancer has been made in the UK since
      the publication of the RCR guidance document.

PMID- 21843929
TI  - Testosterone and resistance training effects on muscle nitric oxide synthase
      isoforms in COPD men.
AB  - BACKGROUND: Skeletal muscle dysfunction contributes to exercise limitation in
      COPD. The role of the nitric oxide synthase (NOS) system in muscle dysfunction is
      ill defined. Reduced levels of endothelial NOS (eNOS) and elevated levels of
      inducible NOS (iNOS) in the skeletal muscle of COPD patients have been recently
      reported. We hypothesized that resistance exercise training (R) and/or
      testosterone supplementation (T) would alter the transcription and expression of
      the NOS isoenzymes in COPD skeletal muscle. METHODS: Vastus lateralis biopsies
      were obtained before and after a 10-week intervention in 40 men with severe
      COPD(age 67.7 +/- 8.3, FEV(1) 41.4 +/- 12.6% predicted): placebo + no training
      (P) (n = 11), placebo + resistance training (PR) (n = 8), testosterone + no
      training (T) (n = 11) and testosterone + resistance training (TR) (n = 10)
      groups. eNOS, nNOS and iNOS mRNA and protein levels were measured in each sample.
      mRNA and protein levels were measured using real-time PCR and enzyme-linked
      immunosorbant assay, respectively. RESULTS: eNOS mRNA increased in the TR group
      compared to P and T groups (P < 0.001). eNOS protein was increased in TR and T
      groups after intervention (P < 0.05) but not in the PR group. nNOS protein
      increased in the PR, T, and TR groups (P < 0.05). iNOS protein decreased only in
      the TR group (P = 0.01). CONCLUSION: Resistance training and testosterone
      supplementation increased eNOS and nNOS proteins and decreased iNOS protein in
      the skeletal muscles of men with COPD. These changes in NO system might explain
      some of the favorable effects of these therapies.

PMID- 21843931
TI  - Ischemia modified albumin in the differential diagnosis of pleural effusions.
AB  - The differential diagnosis of pleural effusion often requires invasive
      procedures. Up to 25 percent of pleural effusions can remain undiagnosed with an
      unclear pathogenesis. Therefore new biological markers may increase diagnostic
      yield and provide better understanding of pathogenesis of pleural effusion. We
      hypothesized that new ischemia biomarker, "ischemia modified albumin (IMA)" would
      help in both the differentiation of the underlying etiologies and provide a
      better understanding of pathogenesis of pleural effusions. This study was done
      between December 2009 and September 2010 in the Department of Pulmonary Diseases
      of Gaziantep University Hospital. One hundred and sixteen subjects with pleural
      effusion were included. Pleural and blood IMA levels were measured by ELISA. The
      underlying etiologies of pleural effusions were as follows: transudates (n = 50),
      malignancy (n = 32), tuberculosis (n = 12), pulmonary thromboembolism (n = 6),
      pneumonia (n = 16). The median pleural IMA levels were significantly different
      between the groups (p < 0.000). There were no such differences in the blood
      levels of IMA. The most striking difference in the median pleural IMA levels was
      between transudates and exudates (7986 (25-75%, 5145-56.505) ng/mL; 3376 (25-75%,
      1935-4660) ng/mL; respectively, p = 0.000). The area under the ROC curve was
      0.837 +/- 0.038 for the cut-off level higher than 4711 ng l/mL for the
      differentiation of transudates from exudates (sensitivity, 82%; specificity, 78%;
      95% CI, 0.76 to 0.91; p = 0.0000). In conclusion, the pleural IMA levels are
      higher in transudates compared to exudates. No such differences were observed in
      blood levels of IMA suggesting that there are reasons other than ischemia that
      cause an increase in pleural fluid IMA levels.

PMID- 21843933
TI  - Effects of temperature and temperature shock on the performance and microbial
      community structure of a submerged anaerobic membrane bioreactor.
AB  - Effects of temperature and temperature shock on the performance and microbial
      community structure of a submerged anaerobic membrane bioreactor (SAnMBR)
      treating thermomechanical pulping pressate were studied for 416 days. The results
      showed that the SAnMBR system were highly resilient to temperature variations in
      terms of chemical oxygen demand (COD) removal. The residual COD in treated
      effluent was slightly higher at 55  degrees C than that at 37 and 45  degrees C.
      There were no significant changes in biogas production rate and biogas
      composition. However, temperature shocks resulted in an increase in biogas
      production temporarily. The SAnMBR could tolerate the 5 and 10  degrees C
      temperature shocks at 37  degrees C and the temperature variations from 37 to 45 
      degrees C. The temperature shock of 5 and 10  degrees C at 45  degrees C led to
      slight and significant disturbance of the performance, respectively. Temperature
      affected the richness and diversity of microbial populations.

PMID- 21843932
TI  - Relative contributions of archaea and bacteria to microbial ammonia oxidation
      differ under different conditions during agricultural waste composting.
AB  - The aim of this study was to compare the relative contribution of ammonia
      oxidizing archaea (AOA) and bacteria (AOB) to nitrification during agricultural
      waste composting. The AOA and AOB amoA gene abundance and composition were
      determined by quantitative PCR and denaturing gradient gel electrophoresis
      (DGGE), respectively. The results showed that the archaeal amoA gene was abundant
      throughout the composting process, while the bacterial amoA gene abundance
      decreased to undetectable level during the thermophilic and cooling stages. DGGE
      showed more diverse archaeal amoA gene composition when the potential ammonia
      oxidation (PAO) rate reached peak values. A significant positive relationship was
      observed between the PAO rate and the archaeal amoA gene abundance (R2=0.554;
      P<0.001), indicating that archaea dominated ammonia oxidation during the
      thermophilic and cooling stages. Bacteria were also related to ammonia oxidation
      activity (R2=0.503; P=0.03) especially during the mesophilic and maturation
      stages.

PMID- 21843934
TI  - Effect of pH and nitrite concentration on nitrite oxidation rate.
AB  - The effect of pH and nitrite concentration on the activity of the nitrite
      oxidizing bacteria (NOB) in an activated sludge reactor has been determined by
      means of laboratory batch experiments based on respirometric techniques. The
      bacterial activity was measured at different pH and at different total nitrite
      concentrations (TNO2). The experimental results showed that the nitrite oxidation
      rate (NOR) depends on the TNO2 concentration independently of the free nitrous
      acid (FNA) concentration, so FNA cannot be considered as the real substrate for
      NOB. NOB were strongly affected by low pH values (no activity was detected at pH
      6.5) but no inhibition was observed at high pH values (activity was nearly the
      same for the pH range 7.5-9.95). A kinetic expression for nitrite oxidation
      process including switch functions to model the effect of TNO2 concentration and
      pH inhibition is proposed. Substrate half saturation constant and pH inhibition
      constants have been obtained.

PMID- 21843935
TI  - Inhibition of COX-1 activity and COX-2 expression by 3-(4'-geranyloxy-3'
      methoxyphenyl)-2-trans propenoic acid and its semi-synthetic derivatives.
AB  - Oxyprenylated naturally occurring cinnamic acids displayed efficient and
      promising biological activities. Aim of this study was to characterize the
      effects of 3-(4'-geranyl-3'-methoxy)phenyl-2-trans propenoic acid and its
      selected semi-synthetic analogues, on COX-2 expression and activity, and on COX-1
      activity, in purified systems or in whole cell systems. The anti-inflammatory
      activity of title compounds (1) was tested as inhibition of COX-2 on isolated
      monocytes stimulated with LPS (10 MUg/ml). COX-2 expression was completely
      suppressed when monocytes were incubated with 100 MUM of 3-(4'-geranyl-3'
      methoxy)phenyl-2-trans propenoic acid (1) or 3-(4'-isopentenyloxy)phenyl-2-trans
      propenoic acid (4). Moreover compounds (1) and (4) inhibit dose-dependently LPS
      induced COX-2 expression.

PMID- 21843936
TI  - 3D QSAR and docking study of flavone derivatives as potent inhibitors of
      influenza H1N1 virus neuraminidase.
AB  - Although several flavonoids have been reported to exert inhibitory effects on
      influenza H1N1 neuraminidase (NA), little is known about the structure-activity
      relationship and binding mode. Three dimensional QSAR (quantitative structure
      activity relationship) and molecular docking approaches were applied to explore
      the structural requisites of flavone derivatives for NA inhibitory activity. A
      meaningful QSAR model with R(2) of 0.5968, Q(2) of 0.6457, and Pearson-R value of
      0.8679, was constructed. From the QSAR model, it could be seen how 6-OH, 3'-OH,
      4'-OH, and 8-position substituent affect the NA inhibitory activity. Molecular
      docking study between the most active compound and NA suggested that hydrogen
      bonds, hydrophobic and electrostatic interactions were closely related to NA
      inhibitory activity, 5-OH and 7-OH may be essential for this activity. The
      results provide a set of useful guidelines for the rational design of novel NA
      inhibitors.

PMID- 21843937
TI  - Synthesis and biological evaluation of 4-piperidinecarboxylate and 4
      piperidinecyanide derivatives for T-type calcium channel blockers.
AB  - To obtain selective and potent inhibitor for T-type calcium channel by ligand
      based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives
      were prepared and evaluated for in vitro and in vivo activity against alpha(1G)
      calcium channel. Among them, several compounds showed good T-type calcium channel
      inhibitory activity and minimal off-target activity over hERG channel (%
      inhibition at 10 MUM=61.85-71.99, hERG channel IC(50)=1.57 +/- 0.14-4.98 +/- 0.36
      MUM). Selected compound 31a was evaluated on SNL model of neuropathic pain and
      showed inhibitory effect on mechanical allodynia.

PMID- 21843938
TI  - In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite
      urolithin A.
AB  - Urolithin A is a major metabolite produced by rats and humans after consumption
      of pomegranate juice or pure ellagitannin geraniin. In this study, we
      investigated the anti-inflammatory effect of urolithin A on carrageenan-induced
      paw edema in mice. The volume of paw edema was reduced at 1h after oral
      administration of urolithin A. In addition, plasma in treated mice exhibited
      significant oxygen radical antioxidant capacity (ORAC) scores with high plasma
      levels of the unconjugated form at 1h after oral administration of urolithin A.
      These results indicate strong associations among plasma urolithin A levels, the
      plasma ORAC scores, and anti-inflammatory effects and may help explain a
      mechanism by which ellagitannins confer protection against inflammatory diseases.

PMID- 21843939
TI  - Synthesis and cytotoxicity of 8-cyano-3-substitutedalkyl-5-methyl-4-methylene-7
      methoxy-3,4-dihydropyrido[4,3-d]pyrimidines.
AB  - Synthesis and cytotoxicity of 11 4-methylene pyrido[4,3-d]pyrimidines 5a-k were
      described. Cytotoxicity assay results showed that some compounds had much
      stronger antitumor activity than Fluorouracil against KB cell lines. The most
      active compound 5i exhibited high potency against KB, CNE2, MGC-803 cell lines
      with IC(50) values of 0.48, 0.15, 0.59 MUM, respectively. The preliminary
      structure-activity relationships indicated that the introduction of benzyl groups
      bearing electron-donating function groups is favorable for the activity.

PMID- 21843940
TI  - Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of
      tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents.
AB  - Multidrug resistance in tumor cells poses a major obstacle to efficient
      chemotherapy. Several types of agents have been recognized as multidrug
      resistance inhibitors, among which the tetrahydroisoquinolines is the most
      studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of
      tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects
      in reversing multidrug resistance have been evaluated. The results revealed that
      these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed
      higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line.
      Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02
      cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l
      significantly increased the intracellular accumulation of rhodamine123 in
      K562/A02 cells. Furthermore, these three compounds produced high concentrations
      of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by
      NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our
      results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well
      as multidrug resistance reversal effects.

PMID- 21843941
TI  - Pyrrolidin-3-yl-N-methylbenzamides as potent histamine 3 receptor antagonists.
AB  - On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine
      benzamides (1), a series of related pyrrolidin-3-yl-N-methylbenzamides were
      synthesized and evaluated as H(3) receptor antagonists. In particular, compound
      32 exhibits potent H(3) receptor binding affinity, improved pharmaceutical
      properties and a favorable in vivo profile.

PMID- 21843942
TI  - Outcome of long term active surveillance for estrogen receptor-positive ductal
      carcinoma in situ.
AB  - INTRODUCTION: An option for active surveillance is not currently offered to
      patients with ductal carcinoma in situ (DCIS); however a small number of women
      decline standard surgical treatment for noninvasive cancer. The purpose of this
      study was to assess outcomes in a cohort of 14 well-informed women who elected
      non-surgical active surveillance with endocrine treatment alone for estrogen
      receptor-positive DCIS. METHODS: Retrospective review of 14 women, 12 of whom
      were enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant
      endocrine therapy prior to definitive surgical management. The patients in this
      report withdrew from the parent study opting instead for active surveillance with
      endocrine treatment and imaging. RESULTS: 8 women had surgery at a median follow
      up of 28.3 months (range 10.1-70 months), 5 had stage I IDC at surgical excision,
      and 3 had DCIS alone. 6 women remain on surveillance without evidence of invasive
      disease for a median of 31.8 months (range 11.8-80.8 months). CONCLUSION: Long
      term active surveillance for DCIS is feasible in a well-informed patient
      population, but is associated with risk of invasive cancer at surgical excision.

PMID- 21843943
TI  - Weekly nab-paclitaxel is safe and effective in >=65 years old patients with
      metastatic breast cancer: a post-hoc analysis.
AB  - PURPOSE: This post-hoc analysis of 2 studies investigated the safety and efficacy
      of weekly and every-3-week (q3w) nanoparticle albumin-bound paclitaxel (nab
      paclitaxel) in older patients with metastatic breast cancer (MBC) compared with
      q3w solvent-based paclitaxel and docetaxel. RESULTS: Patients>=65 years (median:
      69) were analyzed. In phase 2 (n=52), overall response rates (ORR) for weekly nab
      paclitaxel were 60-64% vs 22% for q3w nab-paclitaxel and 32% for docetaxel. In
      phase 3 (n=62), ORRs were 27% for q3w nab-paclitaxel and 19% for solvent-based
      paclitaxel. In phase 2, median progression-free survival (PFS) was 18.9 months
      for 150 mg/m2 weekly nab-paclitaxel vs 8.5-13.8 months for all other regimens. In
      phase 3, median PFS for q3w nab-paclitaxel and solvent-based paclitaxel were 5.6
      months and 3.5 months, respectively. Weekly nab-paclitaxel resulted in less
      serious adverse events compared with all other regimens. CONCLUSIONS: Weekly nab
      paclitaxel was safe and more efficacious compared with the q3w schedule and with
      solvent-based taxanes in older patients with MBC.

PMID- 21843944
TI  - Patients 35 years old or younger with operable breast cancer are more at risk for
      relapse and survival: a retrospective matched case-control study.
AB  - It has long been suggested that younger women with breast cancer have less
      favorable prognostic factors and poorer outcomes. Our main objectives were to
      determine whether poor prognosis among young women was independent of other
      common clinicopathologic parameters. We retrospectively analyzed 551 young
      patients (<= 35 years, Group I) and 551 older patients (36-50 years, Group II),
      matched for year of diagnosis, family history of breast cancer, pathologic stage,
      hormone receptor expression and application of adjuvant therapy. Patients in
      Group I had significantly shorter disease-free survival (DFS) than Group II
      (median 23.2 months vs. 28.4 months, P = 0.024). Five-year DFS rate(63.7% vs.
      74.7%, P < 0.001) and overall survival (OS) rate (79.5% vs. 85.6%, P = 0.024) in
      Group I was inferior to those in Group II. Multivariate analysis showed that
      young age was a significantly negative predictor for DFS and OS. Our study thus
      shows that age (<= 35 y/o) is an independent risk factor for prognosis in
      operable breast cancer.

PMID- 21843930
TI  - Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial.
AB  - BACKGROUND: In COPD patients, hyperinflation impairs cardiac function. We
      examined whether lung deflation improves oxygen pulse, a surrogate marker of
      stroke volume. METHODS: In 129 NETT patients with cardiopulmonary exercise
      testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was
      assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac
      function with oxygen pulse (O(2) pulse=VO(2)/HR) at baseline and 6 months.
      Medical and surgical patients were divided into "deflators" and "non-deflators"
      based on change in RV/TLC from baseline (?RV/TLC). We defined deflation as the
      ?RV/TLC experienced by 75% of surgical patients. We examined changes in O(2)
      pulse at peak and similar (iso-work) exercise. Findings were validated in 718
      patients who underwent CPET without ABGs. RESULTS: In the ABG substudy, surgical
      and medical deflators improved their RV/TLC and peak O(2) pulse (median ?RV/TLC 
      18.0% vs. -9.3%, p=0.0003; median ?O(2) pulse 13.6% vs. 1.8%, p=0.12). Surgical
      deflators also improved iso-work O(2) pulse (0.53 mL/beat, p=0.04 at 20 W). In
      the validation cohort, surgical deflators experienced a greater improvement in
      peak O(2) pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical
      deflators improvements in O(2) pulse at rest and during unloaded pedaling (0.32
      mL/beat, p<0.0001 and 0.47 mL/beat, p<0.0001, respectively) corresponded with
      significant reductions in HR and improvements in VO(2). On multivariate analysis,
      deflators were 88% more likely than non-deflators to have an improvement in O(2)
      pulse (OR 1.88, 95% CI 1.30-2.72, p=0.0008). CONCLUSION: In COPD, decreased
      hyperinflation through lung volume reduction is associated with improved O(2)
      pulse.

PMID- 21843945
TI  - A novel amino-benzosuberone derivative is a picomolar inhibitor of mammalian
      aminopeptidase N/CD13.
AB  - A new class of low molecular weight, highly potent and selective non peptidic
      inhibitors of aminopeptidase N (APN/CD13) is described. We report the synthesis
      and in vitro evaluation of racemic substituted analogues of 7-amino
      benzocyclohepten-6-one 1a. We investigated various substitutions on the aromatic
      ring with phenyl and halogen groups. In vitro kinetic studies revealed that these
      compounds are among the most effective APN/CD13 inhibitors found so far.
      Hydrophobic substituents placed at position 1 or 4 on the cycloheptenone 1a led
      to the potent compounds 1c-h,b'-c',f',h' with K(i) in the nanomolar range. The
      key finding of the present work was the observed additive effect of 1,4
      disubstitutions which led to the discovery of the picomolar inhibitor 1d'
      (K(i)=60 pM). The designed inhibitors retain the selectivity of our lead
      structure 1a towards selected members of the aminopeptidase family, combined with
      an impressive increase in inhibitory potency and a conserved stability.

PMID- 21843946
TI  - Volatile organic compounds from rhizobacteria increase biosynthesis of essential
      oils and growth parameters in peppermint (Mentha piperita).
AB  - Volatile organic compounds (VOCs), characterized by low molecular weight and high
      vapor pressure, are produced by all organisms as part of normal metabolism, and
      play important roles in communication within and between organisms. We examined
      the effects of VOCs released by three species of plant growth-promoting
      rhizobacteria (Pseudomonas fluorescens, Bacillus subtilis, Azospirillum
      brasilense) on growth parameters and composition of essential oils (EO) in the
      aromatic plant Mentha piperita (peppermint). The bacteria and plants were grown
      on the same Petri dish, but were separated by a physical barrier such that the
      plants were exposed only to VOCs but not to solutes from the bacteria. Growth
      parameters of plants exposed to VOCs of P. fluorescens or B. subtilis were
      significantly higher than those of controls or A. brasilense-treated plants.
      Production of EOs (monoterpenes) was increased 2-fold in P. fluorescens-treated
      plants. Two major EOs, (+)pulegone and (-)menthone, showed increased biosynthesis
      in P. fluorescens-treated plants. Menthol in A. brasilense-treated plants was the
      only major EO that showed a significant decrease. These findings suggest that
      VOCs of rhizobacteria, besides inducing biosynthesis of secondary metabolites,
      affect pathway flux or specific steps of monoterpene metabolism. Bacterial VOCs
      are a rich source for new natural compounds that may increase crop productivity
      and EO yield of this economically important plant species.

PMID- 21843947
TI  - Over-expression of a grape stilbene synthase gene in tomato induces parthenocarpy
      and causes abnormal pollen development.
AB  - A novel strategy to induce parthenocarpy in tomato fruits by the induction of
      resveratrol biosynthesis in flower tissues was exploited. Two transgenic tomato
      lines were considered: a higher resveratrol-producing (35SS) line, constitutively
      expressing a grape stilbene synthase cDNA, and a lower resveratrol-producing
      (LoxS) line, expressing stilbene synthase under a fruit-specific promoter. The
      expression of the stilbene synthase gene affected flavonoid metabolism in a
      different manner in the transgenic lines, and in one of these, the 35SS line,
      resulted in complete male sterility. Resveratrol was synthesised either in 35SS
      or LoxS tomato flowers, at an even higher extent (about 8-10 times) in the former
      line. We further investigated whether stilbene synthase expression may have
      resulted in impaired naringenin accumulation during flower development. In the
      35SS flowers, naringenin was significantly impaired by about 50%, probably due to
      metabolic competition. Conversely, the amount of glycosylated flavonols increased
      in transgenic flowers, thereby excluding the diminished production of flavonols
      as a reason for parthenocarpy in tomato. We further investigated whether
      resveratrol synthesis may have resulted changes to pollen structure. Microscopic
      observations revealed the presence of few and abnormal flake-like pollen grains
      in 35SS flowers with no germination capability. Finally, the analysis of coumaric
      and ferulic acids, the precursors of lignin and sporopollenin biosynthesis,
      revealed significant depletion of these compounds, therefore suggesting an
      impairment in structural compounds as a reason for pollen ablation. These overall
      outcomes, to the best of our knowledge, reveal for the first time the major role
      displayed by resveratrol synthesis on parthenocarpy in tomato fruits.

PMID- 21843948
TI  - Effect of self-setting alpha-tricalcium phosphate between segments for bone
      healing and hypoaesthesia in lower lip after sagittal split ramus osteotomy.
AB  - AIMS: The aim of this study was to evaluate hypoaesthesia of the lower lip and
      bone formation using self-setting alpha-tricalcium phosphate (Biopex((r)))
      between the proximal and distal segments following sagittal split ramus osteotomy
      (SSRO) with bent absorbable plate fixation. SUBJECTS AND METHODS: The subjects
      were 40 patients (80 sides) who underwent bilateral SSRO setback surgery. They
      were divided into a Biopex((r)) group (40 sides) and a control group (40 sides).
      The Biopex((r)) was inserted into the anterior part of the gap between the
      segments in the Biopex((r)) group. Trigeminal nerve hypoaesthesia in the region
      of the lower lip was assessed bilaterally using the trigeminal somatosensory
      evoked potential (TSEP) method. Ramus square, ramus length, and ramus width, the
      square of the Biopex((r)) at the horizontal plane under the mandibular foramen
      were assessed preoperatively, immediately after surgery, and 1year
      postoperatively by computed tomography (CT). RESULTS: The mean measurable period
      and standard deviation were 9.3+/-15.7weeks in the control group, 5.3+/-8.3weeks
      in the Biopex((r)) group, and there was no significant difference. Ramus square
      after 1year was significantly larger than that prior to surgery and new bone
      formation was found between the segments in both groups (P<0.05). In the
      Biopex((r)) group, the square of the Biopex((r)) after 1year was significantly
      smaller than that immediately after surgery (P<0.05). CONCLUSION: This study
      suggested that inserting Biopex((r)) in the gap between the proximal and distal
      segments was useful for new bone formation and it did not prevent the recovery of
      lower lip hypoaesthesia after SSRO with bent absorbable plate fixation.

PMID- 21843949
TI  - The potential role of JAK2/STAT3 pathway on the anti-apoptotic effect of
      recombinant human erythropoietin (rhEPO) after experimental traumatic brain
      injury of rats.
AB  - Previous studies indicate that administration of recombinant human erythropoietin
      (rhEPO) protects cortical neurons following traumatic brain injury (TBI). The
      mechanisms of rhEPO's neuroprotection are complex and interacting, including anti
      apoptosis. Here we aim to demonstrate the role of janus kinase 2/signal
      transducer and activator of transcription 3 (JAK2/STAT3) pathway on the anti
      apoptotic effect of rhEPO in Feeney free falling TBI model. Activation of
      JAK2/STAT3 in pericontusional cortex was analyzed among rats in Sham, TBI,
      TBI+rhEPO, TBI+rhEPO+AG490 groups (rhEPO: 5000 U/kg day; JAK2 inhibitor AG490: 5
      mg/kg day, intraperitoneal) through Western blotting, electrophoretic mobility
      shift assay. Bcl-2 and Bcl-xl expression (Q-PCR, Western blotting) and cell
      apoptosis (TUNEL) in pericontusional cortex were also detected in each group. As
      a result, we found that TBI could activate JAK2 and STAT3, and increase cell
      apoptosis in pericontusional cortex. RhEPO enhanced the expression of p-JAK2 and
      p-STAT3, up-regulated the mRNA and protein levels of Bcl-2 and Bcl-xl, followed
      by increased cell survival. Moreover, AG490 attenuated rhEPO's neuroprotection by
      down-regulating rhEPO-induced activation of JAK2/STAT3, and inhibiting Bcl-2 and
      Bcl-xl. These results suggest the essential role of JAK2/STAT3 pathway on the
      anti-apoptotic benefit of post-TBI rhEPO treatment.

PMID- 21843950
TI  - IL-1 acts on T cells to enhance the magnitude of in vivo immune responses.
AB  - IL-1 strikingly enhances antigen-driven responses of CD4 and CD8 T cells. It is
      substantially more effective than LPS and when added to a priming regime of
      antigen plus LPS, it strikingly enhances cell expansion. The effect is mediated
      by direct action on CD4 and CD8 T cells; the response occurs when OT-I or OT-II
      cells are transferred to B6 IL-1R1-/- recipients and only cells that express IL-1
      receptors can respond. The major mechanism through which IL-1 enhances responses
      is by increasing survival of responding cells. IL-1 enhances the proportion of
      responding CD4 T cells that differentiate into Th17 cells and increases the
      proportion of responding CD8 cells that express granzyme B. Of a wide range of
      cytokines tested, only IL-1alpha and IL-1beta mediate this function. The potency
      of IL-1 as an enhancer of T cell responses suggests that it could act to enhance
      responses to weak vaccines and that the pathway utilized by IL-1 might be
      considered in the design of new generations of adjuvants.

PMID- 21843951
TI  - U50,488H inhibits neutrophil accumulation and TNF-alpha induction induced by
      ischemia-reperfusion in rat heart.
AB  - The role of the kappa-opioid receptor in inflammation is not well understood. The
      aim of this study was to investigate whether the kappa-opioid receptor agonist
      U50,488H modulates neutrophil accumulation and TNF-alpha induction in an ischemia
      reperfusion injured rat heart model. Rats were randomly exposed to sham
      operation, myocardial ischemia-reperfusion (MI/R) alone, MI/R+U50,488H,
      MI/R+U50,488H+Wortmannin, and MI/R+U50,488H+L-NAME. The results demonstrated that
      compared to MI/R, U50,488H reduced myocardial infarction area, myocardial
      myeloperoxidase (MPO) levels, serum creatinine kinase (CK) levels, and both serum
      and myocardial TNF-alpha production. Increases were seen in NOx levels in the
      myocardium subjected to MI/R injury. All demonstrated effects of U50,488H were
      abolished by Nor-BNI, a selective kappa-opioid receptor antagonist; Wortmannin, a
      specific PI3K inhibitor; or L-NAME, a nitric oxide synthase (NOS) inhibitor. In
      summary, kappa-opioid receptor stimulation with U50,488H produces both
      cardioprotective and anti-inflammatory effects. These effects may be associated
      with an increase in NO production and the inhibition of neutrophil accumulation
      and TNF-alpha induction via a PI3K sensitive pathway in myocardium subjected to
      MI/R.

PMID- 21843952
TI  - Splice variants of mda-7/IL-24 differentially affect survival and induce
      apoptosis in U2OS cells.
AB  - Interleukin-24 (mda-7/IL-24) is a cytokine in the IL-10 family that has received
      a great deal of attention for its properties as a tumor suppressor and as a
      potential treatment for cancer. In this study, we have identified and
      characterized five alternatively spliced isoforms of this gene. Several, but not
      all of these isoforms induce apoptosis in the osteosarcoma cell line U2OS, while
      none affect the survival of the non-cancerous NOK cell line. One of these
      isoforms, lacking three exons and encoding the N-terminal end of the mda-7/IL-24
      protein sequence, caused levels of apoptosis that were higher than those caused
      by the full-length mda-7/IL-24 variant. Additionally, we found that the ratio of
      isoform expression can be modified by the splice factor SRp55. This regulation
      suggests that alternative splicing of mda-7/IL-24 is under tight control in the
      cell, and can be modified under various cellular conditions, such as DNA damage.
      In addition to providing new insights into the function of an important tumor
      suppressor gene, these findings may also point toward new avenues for cancer
      treatment.

PMID- 21843953
TI  - Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by d
      galactosamine and lipopolysaccharide in mice.
AB  - Interleukin-22 (IL-22), a member of the IL-10 cytokine family that is produced by
      activated Th22, Th1 and Th17 cells as well as natural killer cells, plays an
      important role in increase of innate immunity, protection from damage and
      enhancement of regeneration. Here, we examined the effects of IL-22 on acute
      liver failure model induced by d-galactosamine (GalN) and lipopolysaccharide
      (LPS). Administration of recombinant human IL-22 (rhIL-22) reduced the death rate
      markedly and prevented mice from severe hepatic injury, as evidenced by decreased
      serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity as well
      as improved histological signs in liver. Furthermore, IL-22 treatment decreased
      the hepatic malondialdehyde (MDA) contents and increased the reduced glutathione
      levels. Serum tumor necrosis factor alpha (TNF-alpha) level and hepatic caspase-3
      activity were significantly lower in mice administrated with IL-22. Moreover, IL
      22 treatment significantly enhanced activation of STAT3 and up-regulated the
      expression of Bcl-xL, heme oxygenase-1 (HO-1) and redox factor-1 (Ref-1) in the
      liver injury induced by GalN/LPS. Collectively, these data indicate that IL-22
      can provide critical protection against GalN/LPS-induced liver injury through
      anti-apoptotic, anti-oxidant and anti-inflammatory actions.

PMID- 21843955
TI  - Management of valgus extra-articular calcaneus fracture malunions with a lateral
      opening wedge osteotomy.
AB  - A total of 34 cases of symptomatic valgus deformity of the hindfoot secondary to
      a malunited extra-articular calcaneal fracture were corrected with laterally
      based open wedge calcaneal osteotomy. The pre- and postoperative radiographic
      parameters were compared, and a postoperative clinical evaluation was performed
      using the American Orthopedic Foot and Ankle Society ankle and hindfoot scoring
      system. The mean follow-up period was 56.2 (range 24.1 to 97) months. The most
      significant radiographic changes were improvement in the talonavicular coverage
      angle (mean 17.3 degrees ) on the anteroposterior view. The mean postoperative
      American Orthopedic Foot and Ankle Society hindfoot and ankle score was 90, with
      23 excellent, 8 good, and 3 poor results. Laterally based opening wedge osteotomy
      of the calcaneus is effective in the management of a valgus heel resulting from
      malunited extra-articular calcaneal fractures. Lateral decompression of the
      peroneal tendons and the sural nerve was achieved indirectly through opening
      wedge lateral calcaneal osteotomy that shifted the weight-bearing axis laterally.

PMID- 21843956
TI  - Surgical consideration of in situ prosthetic replacement for primary infected
      abdominal aortic aneurysms.
AB  - OBJECTIVES: To review our surgical experience of primary infected abdominal
      aortic aneurysms, with the aim of assessing the safety and durability of in situ
      prosthetic replacement. DESIGN: Retrospective study in a university hospital.
      MATERIALS AND METHODS: Thirty-four patients who underwent surgery for primary
      infected abdominal aortic aneurysms over the past 18 years were reviewed.
      Operative details and outcomes were recorded for analysis. RESULTS: There were
      six suprarenal and 28 infrarenal infections. Salmonellae (18 patients) were the
      most common pathogens. Thirty patients underwent in situ prosthetic replacement,
      two underwent extra-anatomic bypass and two underwent endovascular repair. The
      surgical mortality for overall patients was 18%, and for patients reconstructed
      in situ, 17%. Among the 30 patients reconstructed in situ, four patients who
      underwent concomitant gastrointestinal procedures (e.g., repair of the duodenal
      defect) died. By contrast, 25 of 26 patients without gastrointestinal involvement
      survived surgery. After a median follow-up period of 58 months, two discharged
      patients who underwent in situ reconstruction died of late graft infection.
      CONCLUSIONS: Our experience suggests that in situ prosthetic replacement can be
      performed safely with durable outcomes in the majority of patients with infected
      abdominal aortic aneurysms. Nevertheless, we advise caution when considering this
      technique with concomitant gastrointestinal procedures.

PMID- 21843957
TI  - Differential protein expression in serum of abdominal aortic aneurysm patients -
      a proteomic approach.
AB  - OBJECTIVE: The aim of the study is to investigate the differential expression of
      proteins in serum of abdominal aortic aneurysm (AAA) patients in relation to
      aneurysm size (D(max)) and progression. METHODS: Two-dimensional differential in
      gel electrophoresis (2D-DIGE) together with tandem mass spectrometry (MS/MS) was
      used to analyse the serum proteome from patients with small (D(max) 30-54 mm)
      AAA, either stable (increase D(max) <5 mm year-1; n = 8) or progressive (increase
      D(max) >=5 mm year-1; n = 8), and large (D(max) >= 55 mm; n = 8) AAA. The
      identified proteins were quantitatively validated in a larger population (n =
      80). RESULTS: Several proteins were differentially expressed in serum of small
      stable, small progressive and large AAA. Three validated proteins (immunoglobulin
      G (IgG), alpha1-antitrypsin (alpha1-AT) and Factor XII activity) showed strong
      correlation with D(max). Size combined with either Factor XII activity or alpha1
      antitrypsin had minimal effect on the prognostic value in predicting aneurysm
      progression compared with size alone (area under the curve (AUC), 0.85; 95%
      confidence interval (CI), 0.73-0.97; p < 0.001 and AUC, 0.85; 95% CI, 0.72-0.98;
      p < 0.001 vs. AUC, 0.83; 95% CI, 0.71-0.96; p < 0.001, respectively). CONCLUSION:
      The present study indicates that both Factor XII and alpha1-antitrypsin are found
      in increased amounts in the serum of patients with expanding AAA. However,
      combination of either Factor XII or alpha1-antitrypsin with aneurysm diameter had
      little effect on prediction of aneurysm progression versus diameter alone.

PMID- 21843958
TI  - Iron chelation therapy in thalassemia major: a systematic review with meta
      analyses of 1520 patients included on randomized clinical trials.
AB  - The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX)
      in thalassemia major was assessed. Outcomes were reported as means+/-SD, mean
      differences with 95% CI, or standardized mean differences. Statistical
      heterogeneity was tested using chi2 (Q) and I2. Sources of bias and Grading of
      Recommendations Assessment, Development and Evaluation system (GRADE) were
      considered. Overall, 1520 patients were included. Only 7.4% of trials were free
      of bias. Overall measurements suggest low trial quality (GRADE). The meta
      analysis suggests lower final liver iron concentrations during associated versus
      monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX
      5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002,
      respectively), but no statistically significant difference during DFX 30 mg/kg
      versus DFO (p=0.70), no statistically significant variations in heart T2* signal
      during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14,
      respectively), increases in urinary iron excretion during associated or
      sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and
      improved ejection fraction during associated or sequential versus monotherapy
      treatment (p=0.01 and p<0.00001, respectively). These findings do not support any
      specific chelation treatment. The literature shows risks of bias, and additional
      larger and longer trials are needed.

PMID- 21843959
TI  - Botulinum toxin type A treatment in children with cerebral palsy: evaluation of
      treatment success or failure by means of goal attainment scaling.
AB  - BACKGROUND: There is considerable variability in the amount of response to BTX-A
      treatment between and within patients with cerebral palsy (CP). AIMS: The purpose
      of this retrospective cohort study was to evaluate the clinical responsiveness of
      Botulinum toxin type A (BTX-A) treatment in children with CP and specifically
      delineate features of treatment success and failure. METHODS: Four hundred and
      thirty-eight children (251 boys, 187 girls; mean age 8 years 2 months, SD 4
      years) were included into the study. Goal Attainment Scaling (GAS) was used to
      classify and evaluate treatment efficacy. Two study groups were defined: one
      group with an excellent response (GAS>=60.0) and one group with a lack of
      response (GAS<=40.0) to BTX-A. RESULTS: Seventy-five patients (17.1%) had an
      excellent response and treatment was found to be unsuccessful for 31 patients
      (7.1%). Children with a lack of response to BTX-A were significantly older
      compared to children with a high responsiveness (p=0.0013). In the latter group,
      more children received multi-level injections and fewer children had injections
      in proximal parts of the lower limb compared to the low responsiveness group
      (p=0.0024). Moreover, there was a significant difference in the use of different
      types of casts between both study groups (p=0.0263). CONCLUSION: Age, level of
      treatment and casting seem to be crucial features of BTX-A treatment success or
      failure in children with CP.

PMID- 21843960
TI  - Role of peripheral versus spinal 5-HT(7)  receptors in the modulation of pain
      undersensitizing conditions.
AB  - Several studies have suggested that 5-HT(7)  receptors are involved in
      nociceptive processing but the exact contribution of peripheral versus central 5
      HT(7)  receptors still needs to be elucidated. In the present study, the
      respective roles of peripheral and spinal 5-HT(7)  receptors in the modulation of
      mechanical hypersensitivity were investigated under two different experimental
      pain conditions. In a first set of experiments, the selective 5-HT(7)  receptor
      agonist, E-57431, was systemically, intrathecally or peripherally
      (intraplantarly) administered to rats sensitized by intraplantar injection of
      capsaicin. Oral administration of E-57431 (1.25-10 mg/kg) was found to exert a
      clear-cut dose-dependent reduction of capsaicin-induced mechanical
      hypersensitivity. Interestingly, intrathecal administration of E-57431 (100 MUg)
      also inhibited mechanical hypersensitivity secondary to capsaicin injection. In
      contrast, a dose-dependent enhancement of capsaicin-induced mechanical
      hypersensitivity was observed after local intraplantar injection of E-57431 (0.01
      1 MUg). In a second set of experiments, E-57431 was systemically or intrathecally
      administered to rats submitted to neuropathic pain (spared nerve injury model).
      Significant inhibition of nerve injury-induced mechanical hypersensitivity was
      found after intraperitoneal (10 mg/kg) as well as intrathecal (100 MUg)
      administration of E-57431 in this chronic pain model. These studies provide
      evidence that, under sensitizing neurogenic/neuropathic conditions, activation of
      5-HT(7)  receptors exerts antinociceptive effects at the level of the spinal cord
      and pronociceptive effects at the periphery. The antinociceptive effect mediated
      by central 5-HT(7)  receptors seems to predominate over the pronociceptive effect
      at the periphery when a selective 5-HT(7)  receptor agonist is systemically
      administered.

PMID- 21843962
TI  - Decreased oxidative phosphorylation and PGAM deficiency in horses suffering from
      atypical myopathy associated with acquired MADD.
AB  - Earlier research on ten horses suffering from the frequently fatal disorder
      atypical myopathy showed that MADD (multiple acyl-CoA dehydrogenase deficiency)
      is the biochemical derangement behind atypical myopathy. From five horses that
      died as a result of this disease and seven healthy control horses, urine and
      plasma were collected ante mortem and muscle biopsies were obtained immediately
      post-mortem (2 patients and 7 control horses), to analyse creatine, purine and
      carbohydrate metabolism as well as oxidative phosphorylation. In patients, the
      mean creatine concentration in urine was increased 17-fold and the concentration
      of uric acid approximately 4-fold, compared to controls. The highest degree of
      depletion of glycogen was observed in the patient with the most severe myopathy
      clinically. In this patient, glycolysis was more active than in the other
      patients and controls, which may explain this depletion. One patient demonstrated
      very low phosphoglycerate mutase (PGAM) activity, less than 10% of reference
      values. Most respiratory chain complex activity in patients was 20-30% lower than
      in control horses, complex II activity was 42% lower than normal, and one patient
      had severely decrease ATP-synthase activity, more than 60% lower than in control
      horses. General markers for myopathic damage are creatine kinase (CK) and lactic
      acid in plasma, and creatine and uric acid in urine. To obtain more information
      about the cause of the myopathy analysis of carbohydrate, lipid and protein
      metabolism as well as oxidative phosphorylation is advised. This study expands
      the diagnostic possibilities of equine myopathies.

PMID- 21843961
TI  - Relaxation times and line widths of isotopically-substituted nitroxides in
      aqueous solution at X-band.
AB  - Optimization of nitroxides as probes for EPR imaging requires detailed
      understanding of spectral properties. Spin lattice relaxation times, spin packet
      line widths, nuclear hyperfine splitting, and overall lineshapes were
      characterized for six low molecular weight nitroxides in dilute deoxygenated
      aqueous solution at X-band. The nitroxides included 6-member, unsaturated 5
      member, or saturated 5-member rings, most of which were isotopically labeled. The
      spectra are near the fast tumbling limit with T(1)~T(2) in the range of 0.50-1.1
      MUs at ambient temperature. Both spin-lattice relaxation T(1) and spin-spin
      relaxation T(2) are longer for (15)N- than for (14)N-nitroxides. The dominant
      contributions to T(1) are modulation of nitrogen hyperfine anisotropy and spin
      rotation. Dependence of T(1) on nitrogen nuclear spin state m(I) was observed for
      both (14)N and (15)N. Unresolved hydrogen/deuterium hyperfine couplings dominate
      overall line widths. Lineshapes were simulated by including all nuclear hyperfine
      couplings and spin packet line widths that agreed with values obtained by
      electron spin echo. Line widths and relaxation times are predicted to be about
      the same at 250 MHz as at X-band.

PMID- 21843963
TI  - Prospective speech outcome study in patients with soft palate reconstruction in
      tonsillar cancer.
AB  - For advanced stage tonsil cancer, extensive resection of the soft palate is
      unavoidable. The purpose of this study is to report on the speech outcome
      according to the various types of defects and reconstruction techniques. This
      prospective study was performed on 53 patients of tonsil cancer. The
      postoperative speech function was evaluated for three factors: nasalance, speech
      intelligibility, and velopharyngeal insufficiency. Four reconstruction methods
      used for the soft palate defect: local flap, patch method, Gehanno method, and
      Denude method. Univariate analysis showed that the Denuded reconstruction
      technique, more than one-half of the soft palate resection, and T stage was
      significantly associated for nasalance, speech intelligibility, and
      velopharyngeal insufficiency. Multivariate analysis showed that the Denuded
      reconstruction technique (for patients with extensive soft palate and posterior
      pharyngeal wall defect) was the most significant variable. When the defect of
      tonsil cancer is extensive, especially when it extends to the posterior
      pharyngeal wall, a reconstruction method that can reduce the velopharyngeal cross
      sectional area efficiently, such as the Gehanno method, is preferred.

PMID- 21843964
TI  - Oscillatory activity in the globus pallidus internus: comparison between
      Parkinson's disease and dystonia.
AB  - OBJECTIVE: Deep brain stimulation in the globus pallidus internus (GPi) is used
      to alleviate the motor symptoms of both Parkinson's disease (PD) and dystonia. We
      tested the hypothesis that PD and dystonia are characterized by different
      temporal patterns of synchronized oscillations in the GPi, and that the
      dopaminergic loss in PD makes the basal ganglia more susceptible to oscillatory
      activity. METHODS: Neuronal firing and local field potentials (LFPs) were
      simultaneously recorded from the GPi in four PD patients and seven dystonia
      patients using two independently driven microelectrodes. RESULTS: In the PD
      patients, beta (11-30 Hz) oscillations were observed in the LFPs and the firing
      activity of ~30% of the neurons was significantly coherent with the LFP. However,
      in the dystonia group, the peak frequency of LFP oscillations was lower (8-20 Hz)
      and there was a significantly smaller proportion of neurons (~10%) firing in
      coherence with the LFP (P<0.001). CONCLUSIONS: These findings suggest that
      synchronization of neuronal firing with LFP oscillations is a more prominent
      feature in PD than in dystonia. SIGNIFICANCE: This study adds to the growing
      evidence that dopaminergic loss in PD may increase the sensitivity of the basal
      ganglia network to rhythmic oscillatory inputs.

PMID- 21843965
TI  - Molecular cloning and characterization of two inducible NAD+-adh genes encoding
      NAD+-dependent alcohol dehydrogenases from Acetobacter pasteurianus SKU1108.
AB  - The cytosolic NAD+-dependent alcohol dehydrogenases (NAD+-ADHs) are induced in
      the quinoprotein ADH-(PQQ-ADH) defective Acetobacter pasteurianus SKU1108 mutant
      during growth in an ethanol medium. The adhI and adhII genes, which encode NAD+
      ADH I and ADH II, respectively, of this strain have been cloned and
      characterized. Sequence analyses have revealed that the adhI gene consists of
      1029 bp coding for 342 amino acids, which share 99.71% identity with the same
      protein from A. pasteurianus IFO 3283. Conversely, the adhII gene is composed of
      762 bp encoding for a polypeptide of 253 amino acids, which exhibit 99.60%
      identity with the A. pasteurianus IFO 3283 protein. ADH I is a member of the
      group I Zn-dependent long-chain ADHs, while the ADH II belongs to the group II
      short-chain dehydrogenase/reductase NAD+-ADHs. The NAD+-adh gene disruptants
      exhibited a growth reduction when grown in an ethanol medium. In Escherichia
      coli, ethanol induced adhI and adhII promoter activities by approximately 1.5 and
      2.0 times, respectively, and the promoter activity of the adhII gene exceeded
      that of the adhI gene by approximately 3.5 times. The possible promoter regions
      of the adhI and adhII genes are located at approximately 81-105 bp and 74-92 bp,
      respectively, from their respective ATG start codons. Their repressor regions
      might be located in proximity to these promoters and may repress gene expression
      in the wild-type, where the membrane-bound ADH effectively functions.

PMID- 21843966
TI  - FSH modulatory effect on human granulosa cells: a gene-protein candidate for
      gonadotrophin surge-attenuating factor.
AB  - Previous evidence indicates a homology of gonadotrophin surge-attenuating factor
      (GnSAF) to the carboxyl terminal of human serum albumin (HSA) and the ability of
      human granulosa cells to produce mRNA transcripts corresponding to this fragment,
      but the underlying mechanism is still unknown. This study investigated the role
      of FSH in vitro in the expression of the carboxyl terminal of HSA by human
      luteinized granulosa cells. Cells were cultured on poly-l-lysine-coated
      microscope slides in the absence or presence of 10 ng/ml FSH, followed by in-situ
      hybridization and immunocytochemistry. In the presence of FSH, mRNA transcripts
      corresponding to the carboxyl terminal of the HSA gene and corresponding protein
      could be detected in comparable intensity to that seen by hepatic HepG2 cells
      (positive control). Significantly lower expression was detected in granulosa
      cells cultured without FSH addition (P<0.01), but no expression was detected in
      HeLa cells. These results demonstrate for the first time that FSH stimulates the
      expression of the carboxyl terminal fragment of the HSA gene and corresponding
      protein in human luteinized granulosa cells. Therefore, the carboxyl terminal of
      HSA has a functional role in the ovary and this further supports the notion that
      this HSA fragment is a GnSAF-bioactive entity.

PMID- 21843967
TI  - Who should control how many embryos to transfer: the state or the patient?

PMID- 21843968
TI  - Efficiency of aseptic open vitrification and hermetical cryostorage of human
      oocytes.
AB  - The present study reports, as far as is known for the first time, the safety of
      UV sterilization of liquid nitrogen and hermetical cryostorage of human oocytes
      by comparing the efficiency of fresh and vitrified sibling oocytes of infertile
      patients. A prospective randomized study on sibling oocytes of 31 patients was
      carried out. Metaphase-II oocytes were randomized for intracytoplasmic sperm
      injection and the supernumerary sibling oocytes were vitrified using a novel
      Cryotop aseptic procedure (UV liquid nitrogen sterilization and hermetical
      cryostorage). After unsuccessful attempts with fresh oocytes, vitrified sibling
      oocytes were injected. Mean outcome measures observed were fertilization,
      cleavage and top-quality embryo rates. No significant differences were observed
      between the fresh and vitrified-warmed sibling oocytes: oocyte fertilization was
      88.3% versus 84.9%; cleavage 72.6% versus 71.0%; top-quality embryos 33.8% versus
      26.3% and mean number of transferred embryos 2.6 +/- 0.1 versus 2.5 +/- 0.1,
      respectively. Clinical pregnancy rate per cycle with vitrified-warmed oocytes was
      35.5% (implantation rate 17.1%) and seven healthy babies were born. This study
      demonstrated that UV liquid nitrogen sterilization and hermetical cryostorage
      does not adversely affect the developmental competence of vitrified oocytes,
      allowing safe aseptic open vitrification applicable under strict directives on
      tissue manipulation.

PMID- 21843969
TI  - Reducing multiple pregnancies after assisted reproduction treatment: Quebec says
      'Yes, we can!'.
AB  - Multiple pregnancy (MP) is widely recognized as the single biggest risk to
      children born as a result of assisted reproduction treatment. There is an
      emerging trend in Europe and Canada to promote single-embryo transfer (SET). In
      this issue, Gleicher argues that twin pregnancies should not be seen as an
      unfavourable outcome of assisted reproduction treatment. He argues that SET
      policies 'make no sense' since they will aggravate already unsatisfactory
      population growth in some countries. He also argues that governmental
      intervention to impose SET policies, despite proving successful in reducing MP,
      are inappropriate. The overwhelming evidence in the literature indicates that his
      opinion is not supported by credible data. Views should be based on solid data
      rather than personal judgement. Governmental interventions to reduce twin
      pregnancies, as demonstrated previously in Belgium and now in Quebec, have been
      successful. The risks of twin pregnancies are real and borne by women and
      children, not their doctors. Doctors managing infertile couples are no longer
      entitled to take risks with the health of the next generation.

PMID- 21843970
TI  - No association between endogenous LH and pregnancy in a GnRH antagonist protocol:
      part II, recombinant FSH.
AB  - The association between endogenous LH concentrations during ovarian stimulation
      in a gonadotrophin-releasing hormone (GnRH) antagonist protocol and pregnancy
      likelihood was examined in a large combined analysis of individualized patient
      data obtained after treatment with recombinant FSH and a GnRH antagonist prior to
      IVF/intracytoplasmic sperm injection. Data from 1764 patients from six randomized
      controlled trials were pooled for retrospective analysis. Ongoing pregnancy and
      miscarriage rates for patients stratified by LH percentiles were assessed.
      Patients in the lowest LH quartile (< P25) were younger with a higher predicted
      ovarian reserve and response compared with patients in the highest quartile (>
      P75). With adjustment for identified predictive factors of pregnancy, estimated
      odds ratios (95% confidence interval) for ongoing pregnancy for LH categories <
      P25 versus >= P25, > P75 versus <= P75 and < P25 versus > P75 were 0.96 (0.75
      1.22), 1.13 (0.88-1.45) and 0.89 (0.66-1.21) on stimulation day 8, and 0.96 (0.76
      1.21), 1.03 (0.82-1.30) and 0.95 (0.72-1.26) on the day of human chorionic
      gonadotrophin, respectively. No significant differences in pregnancy or
      miscarriage rates between the LH categories were observed. Endogenous LH
      concentrations have no association with the likelihood of ongoing pregnancy in
      women undergoing ovarian stimulation using a recombinant FSH/GnRH antagonist
      protocol.

PMID- 21843971
TI  - Azoospermia and paternal autosomal ring chromosomes: case report and literature
      review.
AB  - Two men of the same family presented with ring chromosome 22 and azoospermia. The
      literature on all autosomal ring chromosomes and semen abnormalities was
      reviewed. Autosomal ring chromosomes were often associated with a low sperm
      count. This is probably as a result of gamete instability at meiosis due to the
      ring chromosome which leads to an increased breakdown. In addition, ring
      chromosomes transmitted from the parents may manifest quite differently in the
      progeny. Prior to treating these patients with assisted reproduction, appropriate
      counselling should be offered, in view of the varying phenotypic manifestations
      of ring chromosomes in the resulting progeny, and prenatal diagnosis or
      preimplantation diagnosis must be considered.

PMID- 21843972
TI  - And now for some weighty matters.

PMID- 21843973
TI  - Treatment of status epilepticus with plasmapheresis in a patient with thrombotic
      thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a syndrome with numerous
      neurological manifestations including altered mental status and seizures.
      However, status epilepticus (SE) has rarely been reported in this condition.
      Signs may be transient or fluctuate; however, permanent deficits do occur. Its
      prognosis was once considered uniformly poor, with a high mortality rate. Since
      the introduction of plasma infusions and exchanges, the prognosis of the disease
      has improved dramatically; remissions now occur in 80-90% of patients. Altered
      mental status in TTP often resolves with plasmapheresis. Likewise, we
      successfully treated a patient with thrombotic thrombocytopenic purpura (TTP)
      with pronounced clinical effects of status epilepticus with plasmapheresis and
      steroid treatment.

PMID- 21843974
TI  - Colposcopy in special circumstances: Pregnancy, immunocompromise, including HIV
      and transplants, adolescence and menopause.
AB  - The true value of colposcopy in pregnancy is under debate; the examination may be
      more difficult depending on the gestation at which a woman presents. Cervical
      intraepithelial neoplasia does not have an accelerated progression during
      pregnancy, and treatment is usually deferred until postpartum. The prevalence of
      cervical intraepithelial neoplasia is greater in women with immune compromise.
      Those with human immunodeficiency have a higher prevalence, more persistence and
      less regression of human papillomavirus-related infections. Cervical cancer
      remains an AIDS-defining illness. Women who have had renal transplants also have
      a higher risk of developing cervical intraepithelial neoplasia. By contrast,
      other chronic illnesses that require immunosuppressant therapy do not seem to
      show this added risk. In young women, human papillomavirus infection is common
      and cervical intraepithelial neoplasia is also evident, but regression of these
      lesions is frequent and so conservative review may be appropriate. At the
      menopause, colposcopy is often unsatisfactory. The use of human papillomavirus
      testing for triage of low-grade cytological abnormalities may benefit this age
      group.

PMID- 21843975
TI  - Three-dimensional culture of rabbit nucleus pulposus cells in collagen
      microspheres.
AB  - BACKGROUND: Degenerative disc disease poses an increasing threat to our quality
      of life as we age. Existing treatments have limitations. New treatment modalities
      focusing on biologic rather than surgical approach would be appealing. PURPOSE:
      Culturing intervertebral disc cells in a three-dimensional (3D) model that can
      retain cellular characteristics and phenotype is a critical step toward
      understanding how the disc cells respond to and interact with extrinsic signals
      before better therapeutics can be derived. STUDY DESIGN: In this work, we studied
      the culture of rabbit nucleus pulposus (NP) cells in a collagen microsphere
      system and compared their cell morphology and expression of a few potential
      phenotypic markers with that in monolayer culture. METHODS: Specifically, rabbit
      NP cells isolated from both young and old animals were encapsulated and cultured
      in collagen microspheres with different monomeric concentrations and with
      different cell encapsulation density for different period of time. Evaluation on
      the growth kinetics, the viability, the cell morphology, the expression of Types
      I and II collagen, glycosaminoglycans (GAGs), and Keratin 19, and the
      ultrastructure of the fiber meshwork were conducted to compare the microsphere 3D
      culture system and the traditional monolayer cultures. RESULTS: Nucleus pulposus
      cells in two-dimensional culture lost the phenotypic expression of Type II
      collagen and keratin 19 and expressed Type I collagen. In contrast, the 3D
      collagen microsphere culture system consistently outperformed the traditional
      monolayer culture in maintaining a round morphology and preserving the phenotypes
      of NP cells with persistent expression of Type II collagen and Keratin 19. These
      cells also remodeled the template collagen matrix in the microspheres by
      depositing new matrices, including collagen Type II and GAGs in a cell seeding
      density and collagen concentration dependent manner. CONCLUSIONS: This study
      demonstrates the appeal of the 3D collagen microsphere system for NP cell culture
      over traditional monolayer culture because it preserves the phenotypic
      characteristics of NP cells. This system also enables the NP cells to remodel the
      template collagen matrix by depositing new matrices, suggesting an innovative way
      to reconstitute cell-specific and native tissue-like environment in vitro for
      future studies on stem cell matrix niche and interactions of NP cell with
      extrinsic factors.

PMID- 21843976
TI  - Comparison of clinical and pathologic findings of prostate cancers detected
      through screening versus conventional referral in Brazil.
AB  - INTRODUCTION: Data regarding prostate cancer screening in Brazil are limited. We
      compared features of prostate cancers detected through screening versus those
      referred for treatment in Brazil. PATIENTS AND METHODS: Group I included 500 of
      13,754 men whose cancers were detected through screening, and Group II included
      2731 men referred for treatment through the habitual public health system. We
      used Mann-Whitney and chi(2) tests to compare clinical and pathologic findings,
      considering significant any P < 0.05. RESULTS: Median prostate-specific antigen
      (PSA) was lower among screened patients (5.5 ng/mL versus 10.0 ng/mL; P < 0.001).
      Of the screened patients, 170 (34%) had biopsy Gleason score >= 7, compared with
      1265 (46.3%) in the referred group (P < 0.001). Lymph node metastases were
      suspected in 8.6% of the referred versus 3.2% of the screened men (P = 0.002).
      Distant metastases were more common in the referred men (9.3% vs. 3.0%; P <
      0.001). Only 6.0% of the screened cancers were locally advanced at diagnosis (T3
      or T4) versus 26.5% of the referred (P < 0.001). Screened patients had a higher
      proportion of localized tumors after surgery (67.7% vs. 54.2%; P = 0.002).
      Pathology Gleason scores were also lower among screened men (P < 0.01).
      Lymphadenectomies were performed in 166/636 men (26.1%). No nodal metastases were
      found in screened cancers (0/28; 0.0%), while 6/138 referred cancers (4.3%)
      presented nodal involvement (P = 0.3). CONCLUSION: Clinical and pathologic
      characteristics of screen-detected cancers are more favorable than those of
      tumors diagnosed through the Brazilian health system.

PMID- 21843977
TI  - DNA damage response, genetic instability and cancer: from mechanistic insights to
      personalized treatment.

PMID- 21843978
TI  - Risk factors of tissue-expansion failure in burn-scar reconstruction.
AB  - BACKGROUND: Tissue expansion has become invaluable for burn-scar reconstruction.
      However, its use is hindered by the complications that often result in expansion
      failure. This study attempts to identify the risk factors of expansion failure in
      burn patients, as such factors have not been clearly defined. METHODS: This study
      included 62 tissue expansions in 37 burn patients from January 2001 to June 2009.
      Factors including patient's age, sex, co-morbidities, expander size, implantation
      site, volume injected at implantation, preinflation volume ratio (PVR=volume
      injected at implantation/expander size), final inflation volume ratio
      (FIVR=cumulative volume injected at completion of expansion/expander size) and
      expansion duration were analysed. Cases were allocated into success (n=53) and
      failure (n=9) groups. Logistic regression was used in multivariate analysis for
      identifying predictors of expansion failure. RESULTS: The mean age of the
      patients was 29.6 years. The male to female ratio was 1:1.4. Expansion
      complication and failure rates were 53% (n=33) and 14.5% (n=9), respectively. The
      risk factors statistically correlated to expansion failure (p<0.05) were age,
      expander size, PVR and implantation at lower limb. Expansion of lower limbs
      carried a risk of failure 43 times greater than other sites. CONCLUSION: We
      conclude that tissue expansion should be avoided in older patients and in lower
      limbs. The largest possible expander size and inflation at time of implantation
      should be used to lower the risk of expansion failure.

PMID- 21843979
TI  - Evolution of indications for facial transplantation.
AB  - Face transplantation has the unique potential to restore facial form and function
      in patients with severe facial defects. Current indications for face
      transplantation remain limited by unknown long-term outcomes and the requirements
      for lifelong immunosuppression and substantial plans for reconstruction in case
      of failure. We initially obtained Institutional Review Board approval for partial
      face transplantation in patients with defects comprising 25% of the face and/or
      loss of one or more major facial features. We launched an outcome-oriented face
      transplantation study and screened 13 potential patients between February 2008
      and January 2011. Experience gained during screening motivated the expansion of
      indications to include full facial defects and the consideration of patient
      specific complex issues on a case-by-case basis. Although our programme focuses
      on restoring absent or severely compromised motor and sensory functions, we
      recognise aesthetic appearance as a crucial facial function. Patients are
      extensively educated on the risks and benefits of facial transplantation and then
      allowed to play the main role in the decision-making process, as long as no
      absolute exclusion criteria are present. As we learn more about the long-term
      outcomes of face transplantation and safe reduction of immunosuppression, face
      transplant indications may expand from major unreconstructable defects towards
      potentially minor defects.

PMID- 21843980
TI  - Assessment of mechanical ventricular synchrony in Doberman Pinschers with dilated
      cardiomyopathy.
AB  - OBJECTIVES: Loss of temporal synchrony of myocardial contraction has been shown
      to reduce systolic function and be responsible for disease progression in people.
      The objective of this study is the assessment of inter- and intra ventricular
      synchrony in healthy Doberman Pinschers and those with dilated cardiomyopathy
      (DCM) by use of conventional Doppler and tissue velocity imaging. ANIMALS: A
      total of 60 scans from 35 client-owned Doberman Pinschers presented for cardiac
      evaluation were analysed. METHODS: Retrospective analysis of data. Using the
      European Society of Veterinary Cardiology DCM taskforce scoring system, Doberman
      Pinschers were classified into 4 groups: Control (Group 1; n=12), depressed
      systolic function other than DCM (Group 2; n=9), preclinical DCM (Group 3; n=8)
      and symptomatic DCM (Group 4; n=6). The time intervals between the beginning of
      the QRS complex and the peak velocity of pulmonic flow (Q-P) and the peak aortic
      flow (Q-Ao) were used to assess global synchrony between both ventricles. The
      time intervals between the beginning of the QRS complex and the peak myocardial
      systolic velocity (Q-peak S) and the onset of myocardial systolic velocity (Q
      start S) were measured at the base of the right and left ventricular free wall
      (RVFW and LVFW) and interventricular septum (IVS), and used to determine
      segmental longitudinal inter- and intra ventricular synchrony. RESULTS: No
      significant loss of global or segmental longitudinal inter- or intra ventricular
      synchrony was identified between the groups. CONCLUSION: Impairment of
      longitudinal fibre synchrony does not appear to be significantly associated with
      clinical status of DCM in Doberman Pinschers, although it was identified in
      certain individuals.

PMID- 21843982
TI  - Radial imaging with multipolar magnetic encoding fields.
AB  - We present reconstruction methods for radial magnetic resonance imaging (MRI)
      data which were spatially encoded using a pair of orthogonal multipolar magnetic
      fields for in-plane encoding and parallel imaging. It is shown that a direct
      method exists in addition to iterative reconstruction. Standard direct projection
      reconstruction algorithms can be combined with a previously developed direct
      reconstruction for multipolar encoding fields acquired with Cartesian
      trajectories. The algorithm is simplified by recasting the reconstruction problem
      into polar coordinates. In this formulation distortion and aliasing become
      separate effects. Distortion occurs only along the radial direction and aliasing
      along the azimuthal direction. Moreover, aliased points are equidistantly
      distributed in this representation, and, consequently, Cartesian SENSE is
      directly applicable with highly effective unfolding properties for radio
      frequency coils arranged with a radial symmetry. The direct and iterative methods
      are applied to simulated data to analyze basic properties of the algorithms and
      for the first time also measured in vivo data are presented. The results are
      compared to linear spatial encoding using a radial trajectory and quadrupolar
      encoding using a Cartesian trajectory. The direct reconstruction gives good
      results for fully sampled datasets. Undersampled datasets, however, show star
      shaped artifacts, which are significantly reduced with the iterative
      reconstruction.

PMID- 21843981
TI  - A stochastic multi-scale model of electrical function in normal and depleted ICC
      networks.
AB  - Multi-scale modeling has become a productive strategy for quantifying
      interstitial cells of Cajal (ICC) network structure-function relationships, but
      the lack of large-scale ICC network imaging data currently limits modeling
      progress. The single normal equation simulation (SNESIM) algorithm was utilized
      to generate realistic virtual images of small real wild-type (WT) and 5-HT(2B)
      receptor knockout (Htr2b(-/-)) mice ICC networks. Two metrics were developed to
      validate the performance of the algorithm: 1) network density, which is the
      proportion of ICC in the tissue; and 2) connectivity, which reflects the degree
      of connectivity of the ICC network. Following validation, the SNESIM algorithm
      was modified to allow variation in the degree of ICC network depletion. ICC
      networks from a range of depletion severities were generated, and the electrical
      activity over these networks was simulated. The virtual ICC networks generated by
      the original SNESIM algorithm were similar to that of their real counterparts.
      The electrical activity simulations showed that the maximum current density
      magnitude increased as the network density increased. In conclusion, the SNESIM
      algorithm is an effective tool for generating realistic virtual ICC networks. The
      modified SNESIM algorithm can be used with simulation techniques to quantify the
      physiological consequences of ICC network depletion at various physical scales.

PMID- 21843983
TI  - Accurate and efficient optic disc detection and segmentation by a circular
      transformation.
AB  - Under the framework of computer-aided diagnosis, this paper presents an accurate
      and efficient optic disc (OD) detection and segmentation technique. A circular
      transformation is designed to capture both the circular shape of the OD and the
      image variation across the OD boundary simultaneously. For each retinal image
      pixel, it evaluates the image variation along multiple evenly-oriented radial
      line segments of specific length. The pixels with the maximum variation along all
      radial line segments are determined, which can be further exploited to locate
      both the OD center and the OD boundary accurately. Experiments show that OD
      detection accuracies of 99.75%, 97.5%, and 98.77% are obtained for the STARE
      dataset, the ARIA dataset, and the MESSIDOR dataset, respectively, and the OD
      center error lies around six pixels for the STARE dataset and the ARIA dataset
      which is much smaller than that of state-of-the-art methods ranging 14-29 pixels.
      In addition, the OD segmentation accuracies of 93.4% and 91.7% are obtained for
      STARE dataset and ARIA dataset, respectively, that consists of many severely
      degraded images of pathological retinas that state-of-the-art methods cannot
      segment properly. Furthermore, the algorithm runs in 5 s, which is substantially
      faster than many of the state-of-the-art methods.

PMID- 21843984
TI  - Stability and L2 performance analysis of stochastic delayed neural networks.
AB  - This brief focuses on the robust mean-square exponential stability and   L(2)
      performance analysis for a class of uncertain time-delay neural networks
      perturbed by both additive and multiplicative stochastic noises. New mean-square
      exponential stability and   L(2) performance criteria are developed based on the
      delay partition Lyapunov-Krasovskii functional method and generalized Finsler
      lemma which is applicable to stochastic systems. The analytical results are
      established without involving any model transformation, estimation for cross
      terms, additional free-weighting matrices, or tuning parameters. Numerical
      examples are presented to verify that the proposed approach is both less
      conservative and less computationally complex than the existing ones.

PMID- 21843985
TI  - Passivity analysis for discrete-time stochastic Markovian jump neural networks
      with mixed time delays.
AB  - In this paper, passivity analysis is conducted for discrete-time stochastic
      neural networks with both Markovian jumping parameters and mixed time delays. The
      mixed time delays consist of both discrete and distributed delays. The Markov
      chain in the underlying neural networks is finite piecewise homogeneous. By
      introducing a Lyapunov functional that accounts for the mixed time delays, a
      delay-dependent passivity condition is derived in terms of the linear matrix
      inequality approach. The case of Markov chain with partially unknown transition
      probabilities is also considered. All the results presented depend upon not only
      discrete delay but also distributed delay. A numerical example is included to
      demonstrate the effectiveness of the proposed methods.

PMID- 21843986
TI  - Chaotic simulated annealing by a neural network with a variable delay: design and
      application.
AB  - In this paper, we have three goals: the first is to delineate the advantages of a
      variably delayed system, the second is to find a more intuitive Lyapunov function
      for a delayed neural network, and the third is to design a delayed neural network
      for a quadratic cost function. For delayed neural networks, most researchers
      construct a Lyapunov function based on the linear matrix inequality (LMI)
      approach. However, that approach is not intuitive. We provide a alternative
      candidate Lyapunov function for a delayed neural network. On the other hand, if
      we are first given a quadratic cost function, we can construct a delayed neural
      network by suitably dividing the second-order term into two parts: a self
      feedback connection weight and a delayed connection weight. To demonstrate the
      advantage of a variably delayed neural network, we propose a transiently chaotic
      neural network with variable delay and show numerically that the model should
      possess a better searching ability than Chen-Aihara's model, Wang's model, and
      Zhao's model. We discuss both the chaotic and the convergent phases. During the
      chaotic phase, we simply present bifurcation diagrams for a single neuron with a
      constant delay and with a variable delay. We show that the variably delayed model
      possesses the stochastic property and chaotic wandering. During the convergent
      phase, we not only provide a novel Lyapunov function for neural networks with a
      delay (the Lyapunov function is independent of the LMI approach) but also
      establish a correlation between the Lyapunov function for a delayed neural
      network and an objective function for the traveling salesman problem.

PMID- 21843987
TI  - Deep learning regularized Fisher mappings.
AB  - For classification tasks, it is always desirable to extract features that are
      most effective for preserving class separability. In this brief, we propose a new
      feature extraction method called regularized deep Fisher mapping (RDFM), which
      learns an explicit mapping from the sample space to the feature space using a
      deep neural network to enhance the separability of features according to the
      Fisher criterion. Compared to kernel methods, the deep neural network is a deep
      and nonlocal learning architecture, and therefore exhibits more powerful ability
      to learn the nature of highly variable datasets from fewer samples. To eliminate
      the side effects of overfitting brought about by the large capacity of powerful
      learners, regularizers are applied in the learning procedure of RDFM. RDFM is
      evaluated in various types of datasets, and the results reveal that it is
      necessary to apply unsupervised regularization in the fine-tuning phase of deep
      learning. Thus, for very flexible models, the optimal Fisher feature extractor
      may be a balance between discriminative ability and descriptive ability.

PMID- 21843988
TI  - An efficient camera calibration technique offering robustness and accuracy over a
      wide range of lens distortion.
AB  - In the field of machine vision, camera calibration refers to the experimental
      determination of a set of parameters that describe the image formation process
      for a given analytical model of the machine vision system. Researchers working
      with low-cost digital cameras and off-the-shelf lenses generally favor camera
      calibration techniques that do not rely on specialized optical equipment,
      modifications to the hardware, or an a priori knowledge of the vision system.
      Most of the commonly used calibration techniques are based on the observation of
      a single 3-D target or multiple planar (2-D) targets with a large number of
      control points. This paper presents a novel calibration technique that offers
      improved accuracy, robustness, and efficiency over a wide range of lens
      distortion. This technique operates by minimizing the error between the
      reconstructed image points and their experimentally determined counterparts in
      "distortion free" space. This facilitates the incorporation of the exact lens
      distortion model. In addition, expressing spatial orientation in terms of unit
      quaternions greatly enhances the proposed calibration solution by formulating a
      minimally redundant system of equations that is free of singularities. Extensive
      performance benchmarking consisting of both computer simulation and experiments
      confirmed higher accuracy in calibration regardless of the amount of lens
      distortion present in the optics of the camera. This paper also experimentally
      confirmed that a comprehensive lens distortion model including higher order
      radial and tangential distortion terms improves calibration accuracy.

PMID- 21843989
TI  - A unified spectral-domain approach for saliency detection and its application to
      automatic object segmentation.
AB  - In this paper, a visual attention model is incorporated for efficient saliency
      detection, and the salient regions are employed as object seeds for our automatic
      object segmentation system. In contrast with existing interactive segmentation
      approaches that require considerable user interaction, the proposed method does
      not require it, i.e., the segmentation task is fulfilled in a fully automatic
      manner. First, we introduce a novel unified spectral-domain approach for saliency
      detection. Our visual attention model originates from a well-known property of
      the human visual system that the human visual perception is highly adaptive and
      sensitive to structural information in images rather than nonstructural
      information. Then, based on the saliency map, we propose an iterative self
      adaptive segmentation framework for more accurate object segmentation. Extensive
      tests on a variety of cluttered natural images show that the proposed algorithm
      is an efficient indicator for characterizing the human perception and it can
      provide satisfying segmentation performance.

PMID- 21843990
TI  - Multiple descriptions coinciding lattice vector quantizer for wavelet image
      coding.
AB  - Multiple description (MD) coding has been a popular choice for robust data
      transmission over the unreliable network channels. Lattice vector quantization
      provides lower computation for efficient data compression. In this paper, a new
      MD coinciding lattice vector quantizer (MDCLVQ) is presented. The design of the
      quantizer is based on coinciding 2-D hexagonal sublattices. The coinciding
      sublattices are geometrically similar sublattices, with the same index but
      generated by different generator matrices. A novel labeling algorithm based on
      the hexagonal coinciding sublattices is also developed. Performance results of
      the MDCLVQ scheme, together with the new labeling algorithm applied to standard
      test images, show improvements of the central and side decoders, as compared with
      the renowned techniques for several test images.

PMID- 21843991
TI  - Reciprocal focus profile.
AB  - A focus profile having a steeper peak is more resistant to image noise in the
      autofocus (AF) process of a digital camera. However, a focus profile of such
      shape normally has a flatter out-of-focus region on either side of the profile,
      resulting in a slow AF process due to the lack of clue about where the lens
      should move when the lens is in such regions. To address the problem, we provide
      a statistical analysis of the focus profile and show that a strictly monotonic
      transformation of the focus profile preserves the accuracy of the AF. On the
      basis of this analysis, we propose a new focus profile representation that
      transforms the focus profile to the reciprocal domain in which the reciprocal
      focus profile is modeled by a polynomial function. This transformation makes the
      AF mathematically tractable and boosts the search speed. Experimental results are
      shown to demonstrate the advantage of the proposed representation.

PMID- 21843992
TI  - CT reconstruction from parallel and fan-beam projections by a 2-D discrete Radon
      transform.
AB  - The discrete Radon transform (DRT) was defined by Abervuch as an analog of the
      continuous Radon transform for discrete data. Both the DRT and its inverse are
      computable in O(n(2) log n) operations for images of size n * n. In this paper,
      we demonstrate the applicability of the inverse DRT for the reconstruction of a 2
      D object from its continuous projections. The DRT and its inverse are shown to
      model accurately the continuum as the number of samples increases. Numerical
      results for the reconstruction from parallel projections are presented. We also
      show that the inverse DRT can be used for reconstruction from fan-beam
      projections with equispaced detectors.

PMID- 21843993
TI  - Critically sampled wavelets with composite dilations.
AB  - Wavelets with composite dilations provide a general framework for the
      construction of waveforms defined not only at various scales and locations, as
      traditional wavelets, but also at various orientations and with different scaling
      factors in each coordinate. As a result, they are useful to analyze the geometric
      information that often dominate multidimensional data much more efficiently than
      traditional wavelets. The shearlet system, for example, is a particular well
      known realization of this framework, which provides optimally sparse
      representations of images with edges. In this paper, we further investigate the
      constructions derived from this approach to develop critically sampled wavelets
      with composite dilations for the purpose of image coding. Not only do we show
      that many nonredundant directional constructions recently introduced in the
      literature can be derived within this setting, but we also introduce new
      critically sampled discrete transforms that achieve much better nonlinear
      approximation rates than traditional discrete wavelet transforms and outperform
      the other critically sampled multiscale transforms recently proposed.

PMID- 21843994
TI  - A Kalman-filtering approach to high dynamic range imaging for measurement
      applications.
AB  - High dynamic range imaging (HDRI) methods in computational photography address
      situations where the dynamic range of a scene exceeds what can be captured by an
      image sensor in a single exposure. HDRI techniques have also been used to
      construct radiance maps in measurement applications; unfortunately, the design
      and evaluation of HDRI algorithms for use in these applications have received
      little attention. In this paper, we develop a novel HDRI technique based on pixel
      by-pixel Kalman filtering and evaluate its performance using objective metrics
      that this paper also introduces. In the presented experiments, this new technique
      achieves as much as 9.4-dB improvement in signal-to-noise ratio and can achieve
      as much as a 29% improvement in radiometric accuracy over a classic method.

PMID- 21843995
TI  - Framelet-based blind motion deblurring from a single image.
AB  - How to recover a clear image from a single motion-blurred image has long been a
      challenging open problem in digital imaging. In this paper, we focus on how to
      recover a motion-blurred image due to camera shake. A regularization-based
      approach is proposed to remove motion blurring from the image by regularizing the
      sparsity of both the original image and the motion-blur kernel under tight
      wavelet frame systems. Furthermore, an adapted version of the split Bregman
      method is proposed to efficiently solve the resulting minimization problem. The
      experiments on both synthesized images and real images show that our algorithm
      can effectively remove complex motion blurring from natural images without
      requiring any prior information of the motion-blur kernel.

PMID- 21843996
TI  - Nonlinear unsharp masking for mammogram enhancement.
AB  - This paper introduces a new unsharp masking (UM) scheme, called nonlinear UM
      (NLUM), for mammogram enhancement. The NLUM offers users the flexibility 1) to
      embed different types of filters into the nonlinear filtering operator; 2) to
      choose different linear or nonlinear operations for the fusion processes that
      combines the enhanced filtered portion of the mammogram with the original
      mammogram; and 3) to allow the NLUM parameter selection to be performed manually
      or by using a quantitative enhancement measure to obtain the optimal enhancement
      parameters. We also introduce a new enhancement measure approach, called the
      second-derivative-like measure of enhancement, which is shown to have better
      performance than other measures in evaluating the visual quality of image
      enhancement. The comparison and evaluation of enhancement performance demonstrate
      that the NLUM can improve the disease diagnosis by enhancing the fine details in
      mammograms with no a priori knowledge of the image contents. The human-visual
      system-based image decomposition is used for analysis and visualization of
      mammogram enhancement.

PMID- 21843997
TI  - Electromagnetic interference-aware transmission scheduling and power control for
      dynamic wireless access in hospital environments.
AB  - We study the multiple access problem for e-Health applications (referred to as
      secondary users) coexisting with medical devices (referred to as primary or
      protected users) in a hospital environment. In particular, we focus on
      transmission scheduling and power control of secondary users in multiple spatial
      reuse time-division multiple access (STDMA) networks. The objective is to
      maximize the spectrum utilization of secondary users and minimize their power
      consumption subject to the electromagnetic interference (EMI) constraints for
      active and passive medical devices and minimum throughput guarantee for secondary
      users. The multiple access problem is formulated as a dual objective optimization
      problem which is shown to be NP-complete. We propose a joint scheduling and power
      control algorithm based on a greedy approach to solve the problem with much lower
      computational complexity. To this end, an enhanced greedy algorithm is proposed
      to improve the performance of the greedy algorithm by finding the optimal
      sequence of secondary users for scheduling. Using extensive simulations, the
      tradeoff in performance in terms of spectrum utilization, energy consumption, and
      computational complexity is evaluated for both the algorithms.

PMID- 21843998
TI  - Rapid assessment of cardiac contractility on a home bathroom scale.
AB  - Analyzing systolic time intervals-specifically the preejection-period (PEP)-is
      widely accepted as one of the few methods for the noninvasive assessment of
      cardiac contractility. In this paper, we investigated the ballistocardiogram
      (BCG) as a way to noninvasively measure myocardial contractility when combined
      with the ECG. Specifically, we derived a parameter from the BCG and ECG that we
      hypothesized would be highly correlated to PEP. This is the time delay between
      the J-wave peak of the BCG and the R-wave of the ECG, which we refer to as the RJ
      interval. The RJ interval was correlated to PEP (r(2) = 0.86) for 2126 heartbeats
      across ten subjects, with a y-intercept of 138 ms and slope of 1.05. This
      suggests that the RJ interval can be reliably used as a noninvasive assessment of
      cardiac contractility.

PMID- 21843999
TI  - Comprehensive assessment of maize aflatoxin levels in Eastern Kenya, 2005-2007.
AB  - BACKGROUND: Aflatoxin, a potent fungal toxin, contaminates 25% of crops
      worldwide. Since 2004, 477 aflatoxin poisonings associated with eating
      contaminated maize have been documented in Eastern Kenya, with a case-fatality
      rate of 40%. OBJECTIVE: We characterized maize aflatoxin contamination during the
      high-risk season (April-June) after the major harvests in 2005, 2006
      (aflatoxicosis outbreak years), and 2007 (a non-outbreak year). METHODS:
      Households were randomly selected each year from the region in Kenya where
      outbreaks have consistently occurred. At each household, we obtained at least one
      maize sample (n = 716) for aflatoxin analysis using immunoaffinity methods and
      administered a questionnaire to determine the source (i.e., homegrown, purchased,
      or relief) and amount of maize in the household. RESULTS: During the years of
      outbreaks in 2005 and 2006, 41% and 51% of maize samples, respectively, had
      aflatoxin levels above the Kenyan regulatory limit of 20 ppb in grains that were
      for human consumption. In 2007 (non-outbreak year), 16% of samples were above the
      20-ppb limit. In addition, geometric mean (GM) aflatoxin levels were
      significantly higher in 2005 (GM = 12.92, maximum = 48,000 ppb) and 2006 (GM =
      26.03, maximum = 24,400 ppb) compared with 2007 (GM = 1.95, maximum = 2,500 ppb)
      (p-value < 0.001). In all 3 years combined, maize aflatoxin levels were
      significantly higher in homegrown maize (GM = 17.96) when compared with purchased
      maize (GM = 3.64) or relief maize (GM = 0.73) (p-value < 0.0001). CONCLUSIONS:
      Aflatoxin contamination is extreme within this region, and homegrown maize is the
      primary source of contamination. Prevention measures should focus on reducing
      homegrown maize contamination at the household level to avert future outbreaks.

PMID- 21844000
TI  - Climate change, crop yields, and undernutrition: development of a model to
      quantify the impact of climate scenarios on child undernutrition.
AB  - BACKGROUND: Global climate change is anticipated to reduce future cereal yields
      and threaten food security, thus potentially increasing the risk of
      undernutrition. The causation of undernutrition is complex, and there is a need
      to develop models that better quantify the potential impacts of climate change on
      population health. OBJECTIVES: We developed a model for estimating future
      undernutrition that accounts for food and nonfood (socioeconomic) causes and can
      be linked to available regional scenario data. We estimated child stunting
      attributable to climate change in five regions in South Asia and sub-Saharan
      Africa (SSA) in 2050. METHODS: We used current national food availability and
      undernutrition data to parameterize and validate a global model, using a process
      driven approach based on estimations of the physiological relationship between a
      lack of food and stunting. We estimated stunting in 2050 using published modeled
      national calorie availability under two climate scenarios and a reference
      scenario (no climate change). RESULTS: We estimated that climate change will lead
      to a relative increase in moderate stunting of 1-29% in 2050 compared with a
      future without climate change. Climate change will have a greater impact on rates
      of severe stunting, which we estimated will increase by 23% (central SSA) to 62%
      (South Asia). CONCLUSIONS: Climate change is likely to impair future efforts to
      reduce child malnutrition in South Asia and SSA, even when economic growth is
      taken into account. Our model suggests that to reduce and prevent future
      undernutrition, it is necessary to both increase food access and improve
      socioeconomic conditions, as well as reduce greenhouse gas emissions.

PMID- 21844001
TI  - A web-based computerized adaptive testing (CAT) to assess patient perception in
      hospitalization.
AB  - BACKGROUND: Many hospitals have adopted mobile nursing carts that can be easily
      rolled up to a patient's bedside to access charts and help nurses perform their
      rounds. However, few papers have reported data regarding the use of wireless
      computers on wheels (COW) at patients' bedsides to collect questionnaire-based
      information of their perception of hospitalization on discharge from the
      hospital. OBJECTIVE: The purpose of this study was to evaluate the relative
      efficiency of computerized adaptive testing (CAT) and the precision of CAT-based
      measures of perceptions of hospitalized patients, as compared with those of
      nonadaptive testing (NAT). An Excel module of our CAT multicategory assessment is
      provided as an example. METHOD: A total of 200 patients who were discharged from
      the hospital responded to the CAT-based 18-item inpatient perception
      questionnaire on COW. The numbers of question administrated were recorded and the
      responses were calibrated using the Rasch model. They were compared with those
      from NAT to show the advantage of CAT over NAT. RESULTS: Patient measures derived
      from CAT and NAT were highly correlated (r = 0.98) and their measurement
      precisions were not statistically different (P = .14). CAT required fewer
      questions than NAT (an efficiency gain of 42%), suggesting a reduced burden for
      patients. There were no significant differences between groups in terms of gender
      and other demographic characteristics. CONCLUSIONS: CAT-based administration of
      surveys of patient perception substantially reduced patient burden without
      compromising the precision of measuring patients' perceptions of hospitalization.
      The Excel module of animation-CAT on the wireless COW that we developed is
      recommended for use in hospitals.

PMID- 21844002
TI  - Synaptically activated Ca2+ waves and NMDA spikes locally suppress voltage
      dependent Ca2+ signalling in rat pyramidal cell dendrites.
AB  - Postsynaptic [Ca(2+)](i) changes contribute to several kinds of plasticity in
      pyramidal neurons. We examined the effects of synaptically activated Ca(2+) waves
      and NMDA spikes on subsequent Ca(2+) signalling in CA1 pyramidal cell dendrites
      in hippocampal slices. Tetanic synaptic stimulation evoked a localized Ca(2+)
      wave in the primary apical dendrites. The [Ca(2+)](i) increase from a
      backpropagating action potential (bAP) or subthreshold depolarization was reduced
      if it was generated immediately after the wave. The suppression had a recovery
      time of 30-60 s. The suppression only occurred where the wave was generated and
      was not due to a change in bAP amplitude or shape. The suppression also could be
      generated by Ca(2+) waves evoked by uncaging IP(3), showing that other signalling
      pathways activated by the synaptic tetanus were not required. The suppression was
      proportional to the amplitude of the [Ca(2+)](i) change of the Ca(2+) wave and
      was not blocked by a spectrum of kinase or phosphatase inhibitors, consistent
      with suppression due to Ca(2+)-dependent inactivation of Ca(2+) channels. The
      waves also reduced the frequency and amplitude of spontaneous, localized Ca(2+)
      release events in the dendrites by a different mechanism, probably by depleting
      the stores at the site of wave generation. The same synaptic tetanus often evoked
      NMDA spike-mediated [Ca(2+)](i) increases in the oblique dendrites where Ca(2+)
      waves do not propagate. These NMDA spikes suppressed the [Ca(2+)](i) increase
      caused by bAPs in those regions. [Ca(2+)](i) increases by Ca(2+) entry through
      voltage-gated Ca(2+) channels also suppressed the [Ca(2+)](i) increases from
      subsequent bAPs in regions where the voltage-gated [Ca(2+)](i) increases were
      largest, showing that all ways of raising [Ca(2+)](i) could cause suppression.

PMID- 21844003
TI  - Respiratory modulation of muscle sympathetic nerve activity is not increased in
      essential hypertension or chronic obstructive pulmonary disease.
AB  - We examined cardiac and respiratory modulation of muscle sympathetic nerve
      activity (MSNA) in 13 patients with essential hypertension (HT) and 15 with
      chronic obstructive pulmonary disease (COPD), and compared these with a group of
      young healthy controls (YHC) and older healthy controls (OHC). There were no
      significant differences in age of the OHC and HT subjects. MSNA was recorded via
      a tungsten microelectrode inserted percutaneously into the common peroneal nerve.
      Respiration was recorded by a strain-gauge transducer around the chest and ECG
      recorded by surface electrodes. Cardiac and respiratory modulation of MSNA was
      quantified by fitting polynomials to the cross-correlation histograms constructed
      between the sympathetic spikes and ECG or respiration. Cardiac modulation was
      high across all groups, but was significantly lower in COPD (75.9 +/- 4.4%) than
      in the HT (92.4 +/- 3.0%), OHC (93.7 +/- 1.3%) or YHC (89.1 +/- 1.6%) groups.
      Across all groups, respiratory modulation was significantly lower than cardiac
      modulation. Respiratory modulation in HT (45.2 +/- 5.7%) and COPD (37.5 +/- 6.3%)
      was not higher than in the OHC (47.2 +/- 5.4%) or YHC (49.5 +/- 6.0%) groups. We
      have shown that respiratory modulation of MSNA is present in all groups, is
      consistently lower than the magnitude of cardiac modulation, and is not increased
      in HT or COPD, arguing against an amplified respiratory-sympathetic coupling in
      hypertension. Moreover, given that patients with COPD are chronically asphyxic,
      these data indicate that an increased chemical drive does not increase
      respiratory modulation of MSNA.

PMID- 21844004
TI  - Statistics, probability, significance, likelihood: words mean what we define them
      to mean.

PMID- 21844005
TI  - Attack of the catabolic pathways: muscle wasting in the ICU.

PMID- 21844006
TI  - Dramatic decline in the HIV-1 RNA level over calendar time in a large urban HIV
      practice.
AB  - BACKGROUND: We have previously showed that as antiretroviral therapy has improved
      over time since 1995-1996, the likelihood of achieving virologic suppression has
      also improved. Antiretroviral therapy and antiretroviral therapy guidelines have
      continued to evolve, and we wished to determine the trend in human
      immunodeficiency virus (HIV-1) RNA levels over time in HIV-infected persons
      receiving care in our large urban HIV clinical practice in Baltimore, Maryland.
      METHODS: The HIV-1 RNA level was assessed each year from 1996 through 2010 at the
      date closest to 1 July for all patients in care and followed up in the Johns
      Hopkins HIV Clinical Cohort. The clinic population's median HIV-1 RNA level and
      stratified threshold levels were plotted. The demographic characteristics of the
      population were also assessed over time. RESULTS: From 1996 (shortly after highly
      active antiretroviral therapy [HAART] was introduced) to 2010, the median HIV-1
      RNA level decreased from 10,400 to <200 copies/mL. The proportion of patients
      with an HIV-1 RNA level >500 copies/mL decreased from 75% to only 16% during this
      same period. The population itself became older, had a higher proportion of
      women, and a lower proportion of patients with injection drug use as a
      transmission risk, but it was geographically stable. There was an increase in
      HAART use over time. DISCUSSION: Our results demonstrate the remarkable impact of
      increased use of and improved management with HAART in this urban HIV-infected
      population.

PMID- 21844007
TI  - Antiretroviral therapy: now "it just works".

PMID- 21844008
TI  - New strategies in diffuse large B-cell lymphoma: translating findings from gene
      expression analyses into clinical practice.
AB  - Gene expression profiling has had a major impact on our understanding of the
      biology and heterogeneity of diffuse large B-cell lymphoma (DLBCL). Using this
      technology, investigators can identify biologic subgroups of DLBCL that provide
      unique targets for rational therapeutic intervention. This review summarizes
      these potential targets and updates the progress of clinical development of
      exciting novel agents for the treatment of DLBCL. Results of ongoing studies
      suggest that in the near future, we will be able to use gene expression
      profiling, or an accurate surrogate, to define the best therapeutic approach for
      individual patients with DLBCL.

PMID- 21844009
TI  - Colorectal cancers with microsatellite instability display unique miRNA profiles.
AB  - PURPOSE: microRNAs (miRNA) are small noncoding transcripts that play an important
      role in carcinogenesis. miRNA expression profiles have been shown to discriminate
      between different types of cancers. The aim of this study was to analyze global
      miRNA signatures in various groups of colorectal cancers (CRC) based on the
      presence of microsatellite instability (MSI). EXPERIMENTAL DESIGN: We analyzed
      genome-wide miRNA expression profiles in 54 CRC tissues [22 with Lynch syndrome,
      13 with sporadic MSI due to MLH1 methylation, 19 without MSI (or microsatellite
      stable, MSS)] and 20 normal colonic tissues by miRNA microarrays. Using an
      independent set of MSI-positive samples (13 with Lynch syndrome and 20 with
      sporadic MSI), we developed a miRNA-based predictor to differentiate both types
      of MSI by quantitative reverse transcriptase PCR. RESULTS: We found that the
      expression of a subset of nine miRNAs significantly discriminated between tumor
      and normal colonic mucosa tissues (overall error rate = 0.04). More importantly,
      Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI
      tumors; miR-622, miR-1238, and miR-192 were the most differentially expressed
      miRNAs between these two groups. We developed a miRNA-based predictor capable of
      differentiating between types of MSI in an independent sample set. CONCLUSIONS:
      CRC tissues show distinct miRNA expression profiles compared with normal colonic
      mucosa. The discovery of unique miRNA expression profiles that can successfully
      discriminate between Lynch syndrome, sporadic MSI, and sporadic MSS colorectal
      cancers provides novel insights into the role of miRNAs in colorectal
      carcinogenesis, which may contribute to the diagnosis, prognosis, and treatment
      of this disease.

PMID- 21844010
TI  - Dual EGFR/HER2 inhibition sensitizes prostate cancer cells to androgen withdrawal
      by suppressing ErbB3.
AB  - PURPOSE: Patients with recurrent prostate cancer are commonly treated with
      androgen withdrawal therapy (AWT); however, almost all patients eventually
      progress to castration resistant prostate cancer (CRPC), indicating failure of
      AWT to eliminate androgen-sensitive prostate cancer. The overall goal of these
      studies is to determine whether dual inhibition of the receptor tyrosine kinases
      epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness
      of this treatment in prostate cancer. EXPERIMENTAL DESIGN: We used androgen
      dependent LNCaP cells and its CRPC sublines LNCaP-AI and C4-2. Additional data
      were collected in pRNS-1-1 cells stably expressing a mutant androgen receptor (AR
      T877A), and in nude mice harboring CWR22 tumors. Studies utilized EGFR inhibitors
      erlotinib and AG1478, and HER2 inhibitors trastuzumab and AG879. RESULTS: Dual
      EGFR/HER2 inhibition induced apoptosis selectively in androgen-sensitive prostate
      cancer cells undergoing AWT, but not in the presence of androgens, or in CRPC
      cells. We show that AWT alone failed to induce significant apoptosis in androgen
      dependent cells, due to AWT-induced increase in HER2 and ErbB3, which promoted
      survival by increasing Akt phosphorylation. AWT-induced ErbB3 stabilized the AR
      and stimulated PSA, while it was inactivated only by inhibition of both its
      dimerization partners EGFR and HER2 (prostate cancer cells do not express ErbB4);
      but not the inhibition of any one receptor alone, explaining the success of dual
      EGFR/HER2 inhibition in sensitizing androgen-dependent cells to AWT. The
      effectiveness of the inhibitors in suppressing growth correlated with its ability
      to prevent Akt phosphorylation. CONCLUSION: These studies indicate that dual
      EGFR/HER2 inhibition, administered together with AWT, sensitize prostate cancer
      cells to apoptosis during AWT.

PMID- 21844012
TI  - Adoptive transfer of autologous natural killer cells leads to high levels of
      circulating natural killer cells but does not mediate tumor regression.
AB  - PURPOSE: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate
      regression of metastatic melanoma. However, many patients with cancer are
      ineligible for such treatment because their TIL do not expand sufficiently or
      because their tumors have lost expression of antigens and/or MHC molecules.
      Natural killer (NK) cells are large granular lymphocytes that lyse tumor cells in
      a non-MHC-restricted manner. Therefore, we initiated in a clinical trial to
      evaluate the efficacy of adoptively transferred autologous NK cells to treat
      patients with cancers who were ineligible for treatment with TIL. EXPERIMENTAL
      DESIGN: Patients with metastatic melanoma or renal cell carcinoma were treated
      with adoptively transferred in vitro activated autologous NK cells after the
      patients received a lymphodepleting but nonmyeloablative chemotherapy regimen.
      Clinical responses and persistence of the adoptively transferred cells were
      evaluated. RESULTS: Eight patients were treated with an average of 4.7 * 10(10)
      (+/- 2.1 * 10(10)) NK cells. The infused cells exhibited high levels of lytic
      activity in vitro. Although no clinical responses were observed, the adoptively
      transferred NK cells seemed to persist in the peripheral circulation of patients
      for at least one week posttransfer and, in some patients, for several months.
      However, the persistent NK cells in the circulation expressed significantly lower
      levels of the key activating receptor NKG2D and could not lyse tumor cell targets
      in vitro unless reactivated with IL-2. CONCLUSIONS: The persistent NK cells could
      mediate antibody-dependent cell-mediated cytotoxicity without cytokine
      reactivation in vitro, which suggests that coupling adoptive NK cell transfer
      with monoclonal antibody administration deserves evaluation.

PMID- 21844011
TI  - Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor
      phenotype.
AB  - PURPOSE: We compared the metabolic profiles and the association between LDH-A
      expression and lactate production in two isogenic murine breast cancer cell lines
      and tumors (67NR and 4T1). These cell lines were derived from a single mammary
      tumor and have different growth and metabolic phenotypes. EXPERIMENTAL DESIGN:
      LDH-A expression, lactate concentration, glucose utilization, and oxygen
      consumption were measured in cells, and the potential relationship between tumor
      lactate levels [measured by magnetic resonance spectroscopic imaging (MRSI)] and
      tumor glucose utilization [measured by [(18)F]2-deoxy-2-fluoro-D-glucose positron
      emission tomography ([(18)F]FDG-PET)] was assessed in orthotopic breast tumors
      derived from these cell lines. RESULTS: We show a substantial difference in LDH-A
      expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show
      that small orthotopic 4T1 tumors generate 10-fold more lactate than corresponding
      67NR tumors. The high lactate levels in small primary 4T1 tumors are associated
      with intense pimonidazole staining (a hypoxia indicator). Less-intense hypoxia
      staining was observed in the larger 67NR tumors and is consistent with the
      gradual increase and plateau of lactate concentration in enlarging 67NR tumors.
      CONCLUSIONS: Lactate-MRSI has a greater dynamic range than [(18)F]FDG-PET and may
      be a more sensitive measure with which to evaluate the aggressive and metastatic
      potential of primary breast tumors.

PMID- 21844019
TI  - Renewed transmission of dracunculiasis-Chad, 2010.

PMID- 21844013
TI  - Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous
      disruption of glutathione and thioredoxin metabolism.
AB  - PURPOSE: Cancer cells (relative to normal cells) show increased steady-state
      levels of hydroperoxides that are compensated by increased glucose and
      hydroperoxide metabolism. The current study determined whether inhibitors of
      glucose and hydroperoxide metabolism could induce chemoradiosensitization by
      enhancing oxidative stress in lung cancer cells. EXPERIMENTAL DESIGN: A549 and
      NCI-H292 human lung carcinoma cells were treated with 2-deoxy-d-glucose (2DG)
      combined with carboplatin + ionizing radiation (IR). Lung cancer cells were
      further sensitized with inhibitors of glutathione (GSH)- and thioredoxin (Trx)
      dependent metabolism [buthionine sulfoximine (BSO) and auranofin, respectively]
      in vitro and in vivo. RESULTS: When 2DG was combined with carboplatin + IR,
      clonogenic cell killing was enhanced in A549 and NCI-H292 cells, and this
      combination was more effective than paclitaxel + carboplatin + IR. The thiol
      antioxidant (N-acetylcysteine, NAC) was capable of protecting cancer cells from
      2DG + carboplatin -induced cell killing. Simultaneous treatment of cancer cells
      with BSO and auranofin, at doses that were not toxic as single agents, also
      enhanced lung cancer cell killing and sensitivity to 2DG + carboplatin. This
      treatment combination also increased oxidation of both GSH and Trx, which were
      inhibited by NAC. Mice treated with auranofin + BSO showed no alterations in
      circulating leukocytes or red blood cells. Xenograft lung tumor growth in mice
      was more effectively inhibited by treatment with auranofin + BSO + carboplatin
      than animals treated with carboplatin or auranofin + BSO alone. CONCLUSIONS:
      These results show in vitro and in vivo that simultaneous inhibition of GSH and
      Trx metabolism can effectively inhibit lung cancer cell growth and induce
      chemosensitization by a mechanism that involves thiol-mediated oxidative stress.

PMID- 21844020
TI  - Aspergillosis-avoiding a return visit.

PMID- 21844014
TI  - Glutamatergic pathway targeting in melanoma: single-agent and combinatorial
      therapies.
AB  - PURPOSE: Melanoma is a heterogeneous disease where monotherapies are likely to
      fail due to variations in genomic signatures. B-RAF inhibitors have been
      clinically inadequate but response might be augmented with combination therapies
      targeting multiple signaling pathways. We investigate the preclinical efficacy of
      combining the multikinase inhibitor sorafenib or the mutated B-RAF inhibitor
      PLX4720 with riluzole, an inhibitor of glutamate release that antagonizes
      metabotropic glutamate receptor 1 (GRM1) signaling in melanoma cells.
      EXPERIMENTAL DESIGN: Melanoma cell lines that express GRM1 and either wild-type B
      RAF or mutated B-RAF were treated with riluzole, sorafenib, PLX4720, or the
      combination of riluzole either with sorafenib or with PLX4720. Extracellular
      glutamate levels were determined by glutamate release assays. MTT assays and cell
      cycle analysis show effects of the compounds on proliferation, viability, and
      cell-cycle profiles. Western immunoblotting and immunohistochemical staining
      showed apoptotic markers. Consequences on mitogen-activated protein kinase
      pathway were assessed by Western immunoblotting. Xenograft tumor models were used
      to determine the efficacy of the compounds in vivo. RESULTS: The combination of
      riluzole with sorafenib exhibited enhanced antitumor activities in GRM1
      expressing melanoma cells harboring either wild-type or mutated B-RAF. The
      combination of riluzole with PLX4720 showed lessened efficacy compared with the
      combination of riluzole and sorafenib in suppressing the growth of GRM1
      expressing cells harboring the B-RAF(V600E) mutation. CONCLUSIONS: The
      combination of riluzole with sorafenib seems potent in suppressing tumor
      proliferation in vitro and in vivo in GRM1-expressing melanoma cells regardless
      of B-RAF genotype and may be a viable therapeutic clinical combination.

PMID- 21844021
TI  - An end to the era of the US HIV entry ban.

PMID- 21844022
TI  - Does monastic life predispose to the risk of Saint Anthony's fire (herpes
      zoster)?
AB  - BACKGROUND: The consequences of the epidemiology of varicella for zoster
      epidemiology are still debated. We therefore compared the frequency of herpes
      zoster in an adult population with virtually no varicella zoster virus (VZV)
      exposure with that in the general population (GP). METHODS: We performed a
      national, multicenter, observational, exposed versus nonexposed, comparative
      study. The nonexposed population consisted of members of contemplative monastic
      orders (CMO) of the Roman Catholic Church living in 40 isolated monasteries in
      France. The exposed population consisted of a sample of the GP representative of
      the French population in terms of age group, sex, socio-occupational categories,
      and regions. RESULTS: The primary analysis population comprised 920 members of
      CMO (41.5% nuns; mean age, 64.2 years) and 1533 members of the GP (51.9% women;
      mean age, 64.6 years). The reported frequency of zoster was 16.2% among CMO and
      15.1% in the GP (P = .27, adjusted for sex and age). The reported mean age of
      onset of zoster was 54.8 and 48.6 years, respectively (P = .06). CONCLUSIONS:
      This study failed to demonstrate an increased risk or earlier onset of zoster in
      members of CMO not exposed to VZV, compared with that in the GP. Although adults
      highly exposed to VZV could have a reduced risk of zoster, compared with the GP,
      our results suggest that the opposite is not true: adults not exposed to VZV are
      not at increased risk of zoster when compared with the GP, challenging the
      relevance of the assumptions and forecasts of current epidemiological models.

PMID- 21844023
TI  - Absence of exposure to varicella does not increase the risk of zoster.

PMID- 21844024
TI  - Obesity and respiratory hospitalizations during influenza seasons in Ontario,
      Canada: a cohort study.
AB  - BACKGROUND: Previous studies suggest that obesity may be a risk factor for
      complications from pandemic influenza A(H1N1) infection. We aimed to examine the
      association between obesity and respiratory hospitalizations during seasonal
      influenza epidemics and to determine the extent of this association among
      individuals without established risk factors for serious complications due to
      influenza infection. METHODS: We conducted a cohort study over 12 influenza
      seasons (1996-1997 through 2007-2008) of 82545 respondents to population health
      surveys in Ontario, Canada. We included individuals aged 18-64 years who had
      responded to a survey within 5 years prior to the start of an influenza season.
      We used logistic regression to examine the association between self-reported body
      mass index (BMI) and hospitalization for selected respiratory diseases (pneumonia
      and influenza, acute respiratory diseases, and chronic lung diseases), both in
      the entire cohort and stratified by chronic condition status. RESULTS: Obese
      class I (BMI, 30-34.9) (odds ratio [OR], 1.45 [95% confidence interval {CI}, 1.03
      2.05]) and obese class II or III (BMI, >=35) individuals (OR, 2.12 [95% CI, 1.45
      3.10]) were more likely than normal weight individuals to have a respiratory
      hospitalization during influenza seasons. Among obese class II or III
      individuals, the association was present both for those without previously
      identified risk factors (OR, 5.10 [95% CI, 2.53-10.24]) and for those with 1 risk
      factor (OR, 2.11 [95% CI, 1.10-4.06]). CONCLUSIONS: Severely obese individuals
      with and without chronic conditions are at increased risk for respiratory
      hospitalizations during influenza seasons. They should be considered a priority
      group for preventive influenza measures, such as vaccination and treatment with
      antiviral medications.

PMID- 21844025
TI  - Obesity and influenza.

PMID- 21844026
TI  - Inflammatory responses to individual microorganisms in the lungs of children with
      cystic fibrosis.
AB  - BACKGROUND: We hypothesized that the inflammatory response in the lungs of
      children with cystic fibrosis (CF) would vary with the type of infecting
      organism, being greatest with Pseudomonas aeruginosa and Staphylococcus aureus.
      METHODS: A microbiological surveillance program based on annual bronchoalveolar
      lavage (BAL) collected fluid for culture and assessment of inflammation was
      conducted. Primary analyses compared inflammation in samples that grew a single
      organism with uninfected samples in cross-sectional and longitudinal analyses.
      RESULTS: Results were available for 653 samples from 215 children with CF aged 24
      days to 7 years. A single agent was associated with pulmonary infection (>=10(5)
      cfu/mL) in 67 BAL samples, with P. aeruginosa (n = 25), S. aureus (n = 17), and
      Aspergillus species (n = 19) being the most common. These microorganisms were
      associated with increased levels of inflammation, with P. aeruginosa being the
      most proinflammatory. Mixed oral flora (MOF) alone was isolated from 165 BAL
      samples from 112 patients, with 97 of these samples having a bacterial density
      >=10(5) cfu/mL, and was associated with increased pulmonary inflammation (P <
      .001). For patients with current, but not past, infections there was an
      association with a greater inflammatory response, compared with those who were
      never infected (P < .05). However, previous infection with S. aureus was
      associated with a greater inflammatory response in subsequent BAL. CONCLUSIONS:
      Pulmonary infection with P. aeruginosa, S. aureus, or Aspergillus species and
      growth of MOF was associated with significant inflammatory responses in young
      children with CF. Our data support the use of specific surveillance and
      eradication programs for these organisms. The inflammatory response to MOF
      requires additional investigation.

PMID- 21844027
TI  - Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile
      infection in individuals taking concomitant antibiotics for other concurrent
      infections.
AB  - BACKGROUND: Treatment guidelines recommend stopping all implicated antibiotics at
      the onset of Clostridium difficile infection (CDI), but many individuals have
      persistent or new infections necessitating the use of concomitant antibiotics
      (CAs). We used data from 2 phase 3 trials to study effects of CAs on response to
      fidaxomicin or vancomycin. METHODS: Subjects with CDI were treated for 10 days
      with fidaxomicin 200 mg every 12 hours or vancomycin 125 mg every 6 hours,
      assessed for resolution of symptoms, and followed up for an additional 4 weeks
      for evidence of recurrence. Rates of cure, recurrence, and global cure (cure
      without recurrence) were determined for subgroups of subjects defined by CA use
      and treatment group. RESULTS: CAs were prescribed for 27.5% of subjects during
      study participation. The use of CAs concurrent with CDI treatment was associated
      with a lower cure rate (84.4% vs 92.6%; P < .001) and an extended time to
      resolution of diarrhea (97 vs 54 hours; P < .001). CA use during the follow-up
      was associated with more recurrences (24.8% vs 17.7%; not significant), and CA
      administration at any time was associated with a lower global cure rate (65.8% vs
      74.7%; P = .005). When subjects received CAs concurrent with CDI treatment, the
      cure rate was 90.0% for fidaxomicin and 79.4% for vancomycin (P = .04). In
      subjects receiving CAs during treatment and/or follow-up, treatment with
      fidaxomicin compared with vancomycin was associated with 12.3% fewer recurrences
      (16.9% vs 29.2%; P = .048). CONCLUSIONS: Treatment with CAs compromised initial
      response to CDI therapy and durability of response. Fidaxomicin was significantly
      more effective than vancomycin in achieving clinical cure in the presence of CA
      therapy and in preventing recurrence regardless of CA use.

PMID- 21844028
TI  - Serologically confirmed household transmission of 2009 pandemic influenza A
      (H1N1) virus during the first pandemic wave--New York City, April-May 2009.
AB  - BACKGROUND: Understanding transmissibility of influenza viruses within households
      is critical for guiding public health response to pandemics. We studied
      serologically confirmed infection and disease among household contacts of index
      case patients with 2009 pandemic influenza A (H1N1) virus (pH1N1) infection in a
      setting of minimal community pH1N1 transmission. METHODS: We defined index case
      patients as students and staff of a New York City high school with laboratory
      confirmed pH1N1 infection during the earliest phase of the pH1N1 outbreak in
      April 2009. We visited households of index case patients twice, once in early May
      and again in June/July 2009. At each visit, household members (both index case
      patents and household contacts) provided serum samples and completed
      questionnaires about illness and possible risk factors. Serologic testing was
      performed using microneutralization and hemagglutination-inhibition assays.
      RESULTS: Of 79 eligible household contacts in 28 households, 19% had
      serologically confirmed pH1N1 infection, and 28% of those infected were
      asymptomatic. Serologically confirmed infection varied by age among household
      contacts: 36% of contacts younger than 10 years were infected, compared with 46%
      of contacts age 10-18 years, 8% of contacts aged 19-54 years, and 22% of contacts
      aged 55 years and older. CONCLUSIONS: Infection rates were high for household
      contacts of persons with confirmed pH1N1, particularly for contacts aged 10-18
      years, and asymptomatic infection was common. Efforts to reduce household
      transmission during influenza pandemics are important adjuncts to strategies to
      reduce community illness.

PMID- 21844029
TI  - Helical microorganisms in blood smears.

PMID- 21844031
TI  - Late entry to HIV care among Latinos compared with non-Latinos in a southeastern
      US cohort.
AB  - BACKGROUND: Late diagnosis of human immunodeficiency virus (HIV) infection
      remains common despite advances in therapy and prognosis. The southeastern United
      States is a rapidly growing Latino settlement area where ethnic disparities may
      contribute to late presentation to care. METHODS: We assessed demographic and
      clinical factors between racial/ethnic groups at the time of HIV care initiation
      in the University of North Carolina Center for AIDS Research Clinical Cohort. We
      identified independent predictors of late presentation, defined as a CD4(+) T
      lymphocyte (CD4) count <350 cells/mm(3) or an AIDS-defining event (ADE), using
      log-linear binomial regression. RESULTS: During the period 1999-2009, 853
      patients initiated HIV care, of whom 11% were Latino, 28% were white, and 61%
      were black. Median initial CD4 counts were lower for Latino patients (186
      cells/mm(3)) than white patients (292 cells/mm(3); P = .006) and black patients
      (302 cells/mm(3); P = .02). Latino persons were more likely to be late presenters
      than white or black persons (76% vs 58%; P < .001) and accounted for 86%, 75%,
      and 50% of all presenting cases of active tuberculosis, histoplasmosis, and
      toxoplasmosis, respectively. Latino ethnicity, older age, male sex, and earlier
      entry year were independently associated with late presentation (P < .05 for
      all). In multivariable analyses, Latino persons were 1.29 times more likely to
      present to care late than white or black persons (95% confidence interval, 1.15
      1.45). CONCLUSIONS: Latinos are more likely to initiate HIV care later in the
      course of illness than are black and white persons and account for a majority of
      several ADEs. Strategies to improve earlier HIV testing among Latinos in new
      settlement areas are needed.

PMID- 21844032
TI  - Latinos and HIV care in the Southeastern United States: new challenges
      complicating longstanding problems.

PMID- 21844030
TI  - Public health implications for adequate transitional care for HIV-infected
      prisoners: five essential components.
AB  - In the United States, 10 million inmates are released every year, and human
      immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome
      (AIDS) prevalence is several-fold greater in criminal justice populations than in
      the community. Few effective linkage-to-the-community programs are currently
      available for prisoners infected with HIV. As a result, combination
      antiretroviral therapy (cART) is seldom continued after release, and virological
      and immunological outcomes worsen. Poor HIV treatment outcomes result from a
      myriad of obstacles that released prisoners face upon reentering the community,
      including homelessness, lack of medical insurance, relapse to drug and alcohol
      use, and mental illness. This article will focus on 5 distinct factors that
      contribute significantly to treatment outcomes for released prisoners infected
      with HIV and have profound individual and public health implications: (1)
      adaptation of case management services to facilitate linkage to care; (2)
      continuity of cART; (3) treatment of substance use disorders; (4) continuity of
      mental illness treatment; and (5) reducing HIV-associated risk-taking behaviors
      as part of secondary prevention.

PMID- 21844033
TI  - Sex differences in the incidence of peripheral neuropathy among Kenyans
      initiating antiretroviral therapy.
AB  - BACKGROUND: Peripheral neuropathy (PN) is common among patients receiving
      antiretroviral therapy (ART) in resource-limited settings. We report the
      incidence of and risk factors for PN among human immunodeficiency virus (HIV)
      infected Kenyan adults initiating ART. METHODS: An inception cohort was formed of
      adults initiating ART. They were screened for PN at baseline and every 3 months
      for 1 year. We used the validated Brief Peripheral Neuropathy Screen (BPNS) that
      includes symptoms and signs (vibration perception and ankle reflexes) of PN.
      RESULTS: Twenty-two (11%) of 199 patients had PN at baseline screening. One
      hundred fifty patients without evidence of PN at baseline were followed for a
      median of 366 days (interquartile range, 351-399). The incidence of PN was 11.9
      per 100 person-years (95% confidence interval [CI], 6.9-19.1) and was higher in
      women than men (17.7 vs 1.9 per 100 person-years; rate ratio, 9.6; 95% CI, 1.27
      72, P = .03). In stratified analyses, female sex remained statistically
      significant after adjustment for each of the following variables: age, CD4 cell
      count, body mass index, ART regimen, and tuberculosis treatment. Stratifying
      hemoglobin levels decreased the hazard ratio from 9.6 to 7.40 (P = .05), with
      higher levels corresponding to a lower risk of PN. CONCLUSIONS: HIV-infected
      Kenyan women were almost 10 times more likely than men to develop PN in the first
      year of ART. The risk decreased slightly at higher hemoglobin levels. Preventing
      or treating anemia in women before ART initiation and implementing BPNS during
      the first year of ART, the period of highest risk, could ameliorate the risk of
      PN.

PMID- 21844037
TI  - The European Medicines Agency: an overview of its mission, responsibilities, and
      recent initiatives in cancer drug regulation.
AB  - The European Medicines Agency (EMA) is responsible for the scientific evaluation
      of medicines developed by pharmaceutical companies for use in the European Union
      (EU). Since 2005, the agency has become responsible for the approval of all new
      oncology drugs in the EU. In this article we describe the mission, role, and
      responsibilities of the EMA, and provide a brief summary of recent initiatives
      related to cancer drug regulation. The EMA recently published its Road Map to
      2015. Over the next 5 years, the agency aims to continue to stimulate drug
      development in areas of unmet medical needs. Concerning drug safety, one of the
      priorities over the next few years will be to establish a more proactive approach
      in ensuring patient safety. This is the result of new EU legislation coming into
      force in 2012 that will strengthen the way the safety of medicines for human use
      is monitored in the EU. In terms of its general operation, the agency is
      committed to increased openness and transparency, and to build on its
      interactions with stakeholders, including members of academia, health care
      professionals, patients, and health technology assessment bodies. The agency
      recently created an oncology working party to expand the current guideline for
      the development and evaluation of cancer drugs. The guideline focuses on both
      exploratory and confirmatory studies for different types of agents. The current
      revision will address a number of topics, including the use of biomarkers as an
      integrated part of drug development and the use of progression-free survival as a
      primary endpoint in registration trials.

PMID- 21844038
TI  - The key elements of a comprehensive global mammal conservation strategy.
AB  - A global strategy is necessary to achieve the level of coordination, synergy and
      therefore optimization of resources to achieve the broad goal of conserving
      mammals worldwide. Key elements for the development of such a strategy include:
      an institutional subject that owns the strategy; broad conservation goals,
      quantitative targets derived from them and appropriate indicators; data on the
      distribution of species, their threats, the cost-effectiveness of conservation
      actions; and a set of methods for the identification of conservation priorities.
      Previous global mammal research investigated phylogeny, extinction risk, and the
      species and areas that should be regarded as global conservation priorities. This
      theme issue presents new key elements: an updated Red List Index, a new list of
      evolutionarily distinct and globally endangered species, new high-resolution
      mammal distribution models, a global connectivity analysis and scenarios of
      future mammal distribution based on climate and land-cover change. Area
      prioritization schemes account for mammalian phylogeny, governance and cost
      benefit of measures to abate habitat loss. Three discussion papers lay the
      foundations for the development of a global unifying mammal conservation
      strategy, which should not be further deterred by the knowledge gaps still
      existing.

PMID- 21844039
TI  - The changing fates of the world's mammals.
AB  - A recent complete assessment of the conservation status of 5487 mammal species
      demonstrated that at least one-fifth are at risk of extinction in the wild. We
      retrospectively identified genuine changes in extinction risk for mammals between
      1996 and 2008 to calculate changes in the International Union for Conservation of
      Nature (IUCN) Red List Index (RLI). Species-level trends in the conservation
      status of mammalian diversity reveal that extinction risk in large-bodied species
      is increasing, and that the rate of deterioration has been most accelerated in
      the Indomalayan and Australasian realms. Expanding agriculture and hunting have
      been the main drivers of increased extinction risk in mammals. Site-based
      protection and management, legislation, and captive-breeding and reintroduction
      programmes have led to improvements in 24 species. We contextualize these
      changes, and explain why both deteriorations and improvements may be under
      reported. Although this study highlights where conservation actions are leading
      to improvements, it fails to account for instances where conservation has
      prevented further deteriorations in the status of the world's mammals. The
      continued utility of the RLI is dependent on sustained investment to ensure
      repeated assessments of mammals over time and to facilitate future calculations
      of the RLI and measurement against global targets.

PMID- 21844040
TI  - Investing in evolutionary history: implementing a phylogenetic approach for
      mammal conservation.
AB  - Under the impact of human activity, global extinction rates have risen a thousand
      times higher than shown in the fossil record. The resources available for
      conservation are insufficient to prevent the loss of much of the world's
      threatened biodiversity during this crisis. Conservation planners have been
      forced to prioritize their protective activities, in the context of great
      uncertainty. This has become known as 'the agony of choice'. A range of methods
      have been proposed for prioritizing species for conservation attention; one of
      the most strongly supported is prioritizing those species that maximize
      phylogenetic distinctiveness (PD). We evaluate how a composite measure of
      extinction risk and phylogenetic isolation (EDGE) has been used to prioritize
      species according to their degree of unique evolutionary history (evolutionary
      distinctiveness, ED) weighted by conservation urgency (global endangerment, GE).
      We review PD-based approaches and provide an updated list of EDGE mammals using
      the 2010 IUCN Red List. We evaluate how robust this method is to changes in
      phylogenetic uncertainty, knowledge of taxonomy and extinction risk, and examine
      how mammalian species that rank highly in EDGE score are representative of the
      collective from which they are drawn.

PMID- 21844041
TI  - What spatial data do we need to develop global mammal conservation strategies?
AB  - Spatial data on species distributions are available in two main forms, point
      locations and distribution maps (polygon ranges and grids). The first are often
      temporally and spatially biased, and too discontinuous, to be useful
      (untransformed) in spatial analyses. A variety of modelling approaches are used
      to transform point locations into maps. We discuss the attributes that point
      location data and distribution maps must satisfy in order to be useful in
      conservation planning. We recommend that before point location data are used to
      produce and/or evaluate distribution models, the dataset should be assessed under
      a set of criteria, including sample size, age of data, environmental/geographical
      coverage, independence, accuracy, time relevance and (often forgotten)
      representation of areas of permanent and natural presence of the species.
      Distribution maps must satisfy additional attributes if used for conservation
      analyses and strategies, including minimizing commission and omission errors,
      credibility of the source/assessors and availability for public screening. We
      review currently available databases for mammals globally and show that they are
      highly variable in complying with these attributes. The heterogeneity and
      weakness of spatial data seriously constrain their utility to global and also sub
      global scale conservation analyses.

PMID- 21844042
TI  - Global habitat suitability models of terrestrial mammals.
AB  - Detailed large-scale information on mammal distribution has often been lacking,
      hindering conservation efforts. We used the information from the 2009 IUCN Red
      List of Threatened Species as a baseline for developing habitat suitability
      models for 5027 out of 5330 known terrestrial mammal species, based on their
      habitat relationships. We focused on the following environmental variables: land
      cover, elevation and hydrological features. Models were developed at 300 m
      resolution and limited to within species' known geographical ranges. A subset of
      the models was validated using points of known species occurrence. We conducted a
      global, fine-scale analysis of patterns of species richness. The richness of
      mammal species estimated by the overlap of their suitable habitat is on average
      one-third less than that estimated by the overlap of their geographical ranges.
      The highest absolute difference is found in tropical and subtropical regions in
      South America, Africa and Southeast Asia that are not covered by dense forest.
      The proportion of suitable habitat within mammal geographical ranges correlates
      with the IUCN Red List category to which they have been assigned, decreasing
      monotonically from Least Concern to Endangered. These results demonstrate the
      importance of fine-resolution distribution data for the development of global
      conservation strategies for mammals.

PMID- 21844043
TI  - Global patterns of fragmentation and connectivity of mammalian carnivore habitat.
AB  - Although mammalian carnivores are vulnerable to habitat fragmentation and require
      landscape connectivity, their global patterns of fragmentation and connectivity
      have not been examined. We use recently developed high-resolution habitat
      suitability models to conduct comparative analyses and to identify global
      hotspots of fragmentation and connectivity for the world's terrestrial
      carnivores. Species with less fragmentation (i.e. more interior high-quality
      habitat) had larger geographical ranges, a greater proportion of habitat within
      their range, greater habitat connectivity and a lower risk of extinction. Species
      with higher connectivity (i.e. less habitat isolation) also had a greater
      proportion of high-quality habitat, but had smaller, not larger, ranges, probably
      reflecting shorter distances between habitat patches for species with restricted
      distributions; such species were also more threatened, as would be expected given
      the negative relationship between range size and extinction risk. Fragmentation
      and connectivity did not differ among Carnivora families, and body mass was
      associated with connectivity but not fragmentation. On average, only 54.3 per
      cent of a species' geographical range comprised high-quality habitat, and more
      troubling, only 5.2 per cent of the range comprised such habitat within protected
      areas. Identification of global hotspots of fragmentation and connectivity will
      help guide strategic priorities for carnivore conservation.

PMID- 21844044
TI  - Complete, accurate, mammalian phylogenies aid conservation planning, but not
      much.
AB  - In the face of unprecedented global biodiversity loss, conservation planning must
      balance between refining and deepening knowledge versus acting on current
      information to preserve species and communities. Phylogenetic diversity (PD), a
      biodiversity measure that takes into account the evolutionary relationships
      between species, is arguably a more meaningful measure of biodiversity than
      species diversity, but cannot yet be applied to conservation planning for the
      majority of taxa for which phylogenetic trees have not yet been developed. Here,
      we investigate how the quality of data on the taxonomy and/or phylogeny of
      species affects the results of spatial conservation planning in terms of the
      representation of overall mammalian PD. The results show that the better the
      quality of the biodiversity data the better they can serve as a basis for
      conservation planning. However, decisions based on incomplete data are remarkably
      robust across different levels of degrading quality concerning the description of
      new species and the availability of phylogenetic information. Thus, given the
      level of urgency and the need for action, conservation planning can safely make
      use of the best available systematic data, limited as these data may be.

PMID- 21844045
TI  - Governance factors in the identification of global conservation priorities for
      mammals.
AB  - Global conservation priorities have often been identified based on the
      combination of species richness and threat information. With the development of
      the field of systematic conservation planning, more attention has been given to
      conservation costs. This leads to prioritizing developing countries, where costs
      are generally low and biodiversity is high. But many of these countries have poor
      governance, which may result in ineffective conservation or in larger costs than
      initially expected. We explore how the consideration of governance affects the
      selection of global conservation priorities for the world's mammals in a
      complementarity-based conservation prioritization. We use data on Control of
      Corruption (Worldwide Governance Indicators project) as an indicator of
      governance effectiveness, and gross domestic product per capita as an indicator
      of cost. We show that, while core areas with high levels of endemism are always
      selected as important regardless of governance and cost values, there are clear
      regional differences in selected sites when biodiversity, cost or governance are
      taken into account separately. Overall, the analysis supports the concentration
      of conservation efforts in most of the regions generally considered of high
      priority, but stresses the need for different conservation approaches in
      different continents owing to spatial patterns of governance and economic
      development.

PMID- 21844046
TI  - Prioritizing conservation investments for mammal species globally.
AB  - We need to set priorities for conservation because we cannot do everything,
      everywhere, at the same time. We determined priority areas for investment in
      threat abatement actions, in both a cost-effective and spatially and temporally
      explicit way, for the threatened mammals of the world. Our analysis presents the
      first fine-resolution prioritization analysis for mammals at a global scale that
      accounts for the risk of habitat loss, the actions required to abate this risk,
      the costs of these actions and the likelihood of investment success. We evaluated
      the likelihood of success of investments using information on the past frequency
      and duration of legislative effectiveness at a country scale. The establishment
      of new protected areas was the action receiving the greatest investment, while
      restoration was never chosen. The resolution of the analysis and the
      incorporation of likelihood of success made little difference to this result, but
      affected the spatial location of these investments.

PMID- 21844047
TI  - The future of terrestrial mammals in the Mediterranean basin under climate
      change.
AB  - The Mediterranean basin is considered a hotspot of biological diversity with a
      long history of modification of natural ecosystems by human activities, and is
      one of the regions that will face extensive changes in climate. For 181
      terrestrial mammals (68% of all Mediterranean mammals), we used an ensemble
      forecasting approach to model the future (approx. 2100) potential distribution
      under climate change considering five climate change model outputs for two
      climate scenarios. Overall, a substantial number of Mediterranean mammals will be
      severely threatened by future climate change, particularly endemic species.
      Moreover, we found important changes in potential species richness owing to
      climate change, with some areas (e.g. montane region in central Italy) gaining
      species, while most of the region will be losing species (mainly Spain and North
      Africa). Existing protected areas (PAs) will probably be strongly influenced by
      climate change, with most PAs in Africa, the Middle East and Spain losing a
      substantial number of species, and those PAs gaining species (e.g. central Italy
      and southern France) will experience a substantial shift in species composition.

PMID- 21844048
TI  - Future hotspots of terrestrial mammal loss.
AB  - Current levels of endangerment and historical trends of species and habitats are
      the main criteria used to direct conservation efforts globally. Estimates of
      future declines, which might indicate different priorities than past declines,
      have been limited by the lack of appropriate data and models. Given that much of
      conservation is about anticipating and responding to future threats, our
      inability to look forward at a global scale has been a major constraint on
      effective action. Here, we assess the geography and extent of projected future
      changes in suitable habitat for terrestrial mammals within their present ranges.
      We used a global earth-system model, IMAGE, coupled with fine-scale habitat
      suitability models and parametrized according to four global scenarios of human
      development. We identified the most affected countries by 2050 for each scenario,
      assuming that no additional conservation actions other than those described in
      the scenarios take place. We found that, with some exceptions, most of the
      countries with the largest predicted losses of suitable habitat for mammals are
      in Africa and the Americas. African and North American countries were also
      predicted to host the most species with large proportional global declines. Most
      of the countries we identified as future hotspots of terrestrial mammal loss have
      little or no overlap with the present global conservation priorities, thus
      confirming the need for forward-looking analyses in conservation priority
      setting. The expected growth in human populations and consumption in hotspots of
      future mammal loss mean that local conservation actions such as protected areas
      might not be sufficient to mitigate losses. Other policies, directed towards the
      root causes of biodiversity loss, are required, both in Africa and other parts of
      the world.

PMID- 21844049
TI  - Community structure and diversity of tropical forest mammals: data from a global
      camera trap network.
AB  - Terrestrial mammals are a key component of tropical forest communities as
      indicators of ecosystem health and providers of important ecosystem services.
      However, there is little quantitative information about how they change with
      local, regional and global threats. In this paper, the first standardized
      pantropical forest terrestrial mammal community study, we examine several aspects
      of terrestrial mammal species and community diversity (species richness, species
      diversity, evenness, dominance, functional diversity and community structure) at
      seven sites around the globe using a single standardized camera trapping
      methodology approach. The sites-located in Uganda, Tanzania, Indonesia, Lao PDR,
      Suriname, Brazil and Costa Rica-are surrounded by different landscape
      configurations, from continuous forests to highly fragmented forests. We obtained
      more than 51 000 images and detected 105 species of mammals with a total sampling
      effort of 12 687 camera trap days. We find that mammal communities from highly
      fragmented sites have lower species richness, species diversity, functional
      diversity and higher dominance when compared with sites in partially fragmented
      and continuous forest. We emphasize the importance of standardized camera
      trapping approaches for obtaining baselines for monitoring forest mammal
      communities so as to adequately understand the effect of global, regional and
      local threats and appropriately inform conservation actions.

PMID- 21844050
TI  - Mapping and navigating mammalian conservation: from analysis to action.
AB  - Although mammals are often seen as important objects of human interest and
      affection, many are threatened with extinction. A range of efforts have been
      proposed and much work has been done to try to conserve mammals, but there is
      little overall understanding of what has worked and why. As a result, there is no
      global-scale, coordinated approach to conserving all mammals. Rather,
      conservation efforts are usually focused at jurisdictional levels where relevant
      legislation and policies are in force. To help build the framework for a global
      scale approach, in this paper we review the many ways that have been proposed for
      conserving mammals. First, we examine the overall pattern of threat faced by
      mammals at the global level. Secondly, we look at the major structuring issues in
      prioritizing and planning mammal conservation, examining in particular the roles
      of values and scale and a set of approaches to conservation, each of which varies
      along a continuum. Finally, we lay out the steps necessary to move from planning
      to implementing mammalian conservation.

PMID- 21844051
TI  - Reconciling global mammal prioritization schemes into a strategy.
AB  - The huge conservation interest that mammals attract and the large datasets that
      have been collected on them have propelled a diversity of global mammal
      prioritization schemes, but no comprehensive global mammal conservation strategy.
      We highlight some of the potential discrepancies between the schemes presented in
      this theme issue, including: conservation of species or areas, reactive and
      proactive conservation approaches, conservation knowledge and action, levels of
      aggregation of indicators of trend and scale issues. We propose that recently
      collected global mammal data and many of the mammal prioritization schemes now
      available could be incorporated into a comprehensive global strategy for the
      conservation of mammals. The task of developing such a strategy should be
      coordinated by a super-partes, authoritative institution (e.g. the International
      Union for Conservation of Nature, IUCN). The strategy would facilitate funding
      agencies, conservation organizations and national institutions to rapidly
      identify a number of short-term and long-term global conservation priorities, and
      act complementarily to achieve them.

PMID- 21844052
TI  - Estimating the probability of abusive head trauma: a pooled analysis.
AB  - CONTEXT AND OBJECTIVE: To determine which combinations of clinical features
      assist in distinguishing abusive head trauma (AHT) from nonabusive head trauma.
      METHODS: Individual patient data from 6 comparative studies of children younger
      than 3 years with intracranial injury were analyzed to determine the association
      between AHT and combinations of apnea; retinal hemorrhage; rib, skull, and long
      bone fractures; seizures; and head and/or neck bruising. An aggregate analysis of
      data from these studies used multiple imputation of combined clinical features
      using a bespoke hotdeck imputation strategy, which accounted for uncertainty
      arising from missing information. RESULTS: Analyzing 1053 children (348 had AHT),
      excluding nonsignificant variables (gender, age, skull fractures), for a child
      with an intracranial injury and 1 or 2 of the 6 features, the positive predictive
      value (PPV) of AHT varies from 4% to 97% according to the different combinations.
      Although rarely recorded, apnea is significantly associated with AHT (odds ratio
      [OR]: 6.89 [confidence interval: 2.08-22.86]). When rib fracture or retinal
      hemorrhage was present with any 1 of the other features, the OR for AHT is >100
      (PPV > 85%). Any combination of 3 or more of the 6 significant features yielded
      an OR of >100 (PPV for AHT > 85%). CONCLUSIONS: Probabilities of AHT can be
      estimated on the basis of different combinations of clinical features. The model
      could be further developed in a prospective large-scale study, with an expanded
      clinical data set, to contribute to a more refined tool to inform clinical
      decisions about the likelihood of AHT.

PMID- 21844053
TI  - Recurrence risk for autism spectrum disorders: a Baby Siblings Research
      Consortium study.
AB  - OBJECTIVE: The recurrence risk of autism spectrum disorders (ASD) is estimated to
      be between 3% and 10%, but previous research was limited by small sample sizes
      and biases related to ascertainment, reporting, and stoppage factors. This study
      used prospective methods to obtain an updated estimate of sibling recurrence risk
      for ASD. METHODS: A prospective longitudinal study of infants at risk for ASD was
      conducted by a multisite international network, the Baby Siblings Research
      Consortium. Infants (n = 664) with an older biological sibling with ASD were
      followed from early in life to 36 months, when they were classified as having or
      not having ASD. An ASD classification required surpassing the cutoff of the
      Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an
      expert clinician. RESULTS: A total of 18.7% of the infants developed ASD. Infant
      gender and the presence of >1 older affected sibling were significant predictors
      of ASD outcome, and there was an almost threefold increase in risk for male
      subjects and an additional twofold increase in risk if there was >1 older
      affected sibling. The age of the infant at study enrollment, the gender and
      functioning level of the infant's older sibling, and other demographic factors
      did not predict ASD outcome. CONCLUSIONS: The sibling recurrence rate of ASD is
      higher than suggested by previous estimates. The size of the current sample and
      prospective nature of data collection minimized many limitations of previous
      studies of sibling recurrence. Clinical implications, including genetic
      counseling, are discussed.

PMID- 21844054
TI  - Alleged cases of vaccine encephalopathy rediagnosed years later as Dravet
      syndrome.
AB  - Dravet syndrome is a rare epileptic encephalopathy linked to mutations in SCN1A
      (neuronal sodium channel alpha1 subunit) and characterized by an onset in infancy
      with polymorphous seizure types and developmental decline. It was reported
      recently that a proportion of patients previously diagnosed with alleged vaccine
      encephalopathy might possess SCN1A mutations and clinical histories that enabled
      a diagnosis of Dravet syndrome, but these results have not been replicated. We
      present here the cases of 5 children who presented for epilepsy care with
      presumed parental diagnoses of alleged vaccine encephalopathy caused by pertussis
      vaccinations in infancy. Their conditions were all rediagnosed years later, with
      the support of genetic testing, as Dravet syndrome. We hope that these cases will
      raise awareness of Dravet syndrome among health care providers who care for
      children and adolescents and aid in earlier recognition and diagnosis.

PMID- 21844055
TI  - Quality-of-care indicators for children with sickle cell disease.
AB  - OBJECTIVE: To develop a set of quality-of-care indicators for the management of
      children with sickle cell disease (SCD) who are cared for in a variety of
      settings by addressing the broad spectrum of complications relevant to their
      illness. METHODS: We used the Rand/University of California Los Angeles
      appropriateness method, a modified Delphi method, to develop the indicators. The
      process included a comprehensive literature review with ratings of the evidence
      and 2 rounds of anonymous ratings by an expert panel (nominated by leaders of
      various US academic societies and the National Heart, Lung, and Blood Institute).
      The panelists met face-to-face to discuss each indicator in between the 2 rounds.
      RESULTS: The panel recommended 41 indicators that cover 18 topics; 17 indicators
      described routine health care maintenance, 15 described acute or subacute care,
      and 9 described chronic care. The panel identified 8 indicators most likely to
      have a large positive effect on improving quality of life and/or health outcomes
      for children with SCD, which covered 6 topics: timely assessment and treatment of
      pain and fever; comprehensive planning; penicillin prophylaxis; transfusion; and
      the transition to adult care. CONCLUSIONS: Children with SCD are at risk for
      serious morbidities and early mortality, yet efforts to assess and improve the
      quality of their care have been limited compared with other chronic childhood
      conditions. This set of 41 indicators can be used to assess quality of care and
      provide a starting point for quality-improvement efforts.

PMID- 21844056
TI  - Use of models to identify cost-effective interventions: pertussis vaccination for
      pediatric health care workers.
AB  - OBJECTIVE: Acellular pertussis vaccine is safe and effective in adults. An
      explicit recommendation for pertussis booster vaccination in pediatric health
      care workers is based on the importance of health care workers as a potential
      source of infection for patients. However, limited information is available on
      the economic attractiveness of this intervention. We sought to evaluate the
      health-economic attractiveness of a diphtheria-tetanus-acellular pertussis
      booster vaccination program for health care workers in a pediatric intensive care
      setting. METHODS: We developed a Markov model to calculate the cost-effectiveness
      of vaccinating NICU health care workers in different proportions ranging from the
      current strategy of no pertussis booster vaccination program to a vaccination
      program that achieves between 25% and 95% vaccine coverage. RESULTS:
      Implementation of a vaccination program that achieves 25% coverage was projected
      to be cost-saving compared with no vaccine program. At all coverage levels the
      intervention reduced costs, increased life expectancy, and was cost-effective.
      Projections were most sensitive to the risk of a pertussis introduction via an
      infected health care worker. Once the monthly risk of an introduction exceeded
      ~0.3%, implementation of an immunization program with at least 25% coverage
      provided both greater health and greater economic benefits than having no vaccine
      program. CONCLUSIONS: The implementation of a hospital-based and funded
      diphtheria-tetanus-acellular pertussis vaccine program administered through an
      occupational health program is cost-effective or cost-saving in the context of
      pediatric health care facilities in which many of the patients are at risk of
      serious morbidity and mortality should they acquire pertussis while hospitalized.

PMID- 21844057
TI  - Strategies for addressing barriers to publishing pediatric quality improvement
      research.
AB  - BACKGROUND: Advancing the science of quality improvement (QI) requires
      dissemination of the results of QI. However, the results of few QI interventions
      reach publication. OBJECTIVE: To identify barriers to publishing results of
      pediatric QI research and provide practical strategies that QI researchers can
      use to enhance publishability of their work. METHODS: We reviewed and summarized
      a workshop conducted at the Pediatric Academic Societies 2007 meeting in Toronto,
      Ontario, Canada, on conducting and publishing QI research. We also interviewed 7
      experts (QI researchers, administrators, journal editors, and health services
      researchers who have reviewed QI manuscripts) about common reasons that QI
      research fails to reach publication. We also reviewed recently published
      pediatric QI articles to find specific examples of tactics to enhance
      publishability, as identified in interviews and the workshop. RESULTS: We found
      barriers at all stages of the QI process, from identifying an appropriate quality
      issue to address to drafting the manuscript. Strategies for overcoming these
      barriers included collaborating with research methodologists, creating incentives
      to publish, choosing a study design to include a control group, increasing sample
      size through research networks, and choosing appropriate process and clinical
      quality measures. Several well-conducted, successfully published QI studies in
      pediatrics offer guidance to other researchers in implementing these strategies
      in their own work. CONCLUSION: Specific, feasible approaches can be used to
      improve opportunities for publication in pediatric, QI, and general medical
      journals.

PMID- 21844058
TI  - Comparative effectiveness of antibiotic treatment strategies for pediatric skin
      and soft-tissue infections.
AB  - OBJECTIVE: To compare the effectiveness of clindamycin, trimethoprim
      sulfamethoxazole, and beta-lactams for the treatment of pediatric skin and soft
      tissue infections (SSTIs). METHODS: A retrospective cohort of children 0 to 17
      years of age who were enrolled in Tennessee Medicaid, experienced an incident
      SSTI between 2004 and 2007, and received treatment with clindamycin (reference),
      trimethoprim-sulfamethoxazole, or a beta-lactam was created. Outcomes included
      treatment failure and recurrence, defined as an SSTI within 14 days and between
      15 and 365 days after the incident SSTI, respectively. Adjusted models stratified
      according to drainage status were used to estimate the risk of treatment failure
      and time to recurrence. RESULTS: Among the 6407 children who underwent drainage,
      there were 568 treatment failures (8.9%) and 994 recurrences (22.8%). The
      adjusted odds ratios for treatment failure were 1.92 (95% confidence interval
      [CI]: 1.49-2.47) for trimethoprim-sulfamethoxazole and 2.23 (95% CI: 1.71-2.90)
      for beta-lactams. The adjusted hazard ratios for recurrence were 1.26 (95% CI:
      1.06-1.49) for trimethoprim-sulfamethoxazole and 1.42 (95% CI: 1.19-1.69) for
      beta-lactams. Among the 41 094 children without a drainage procedure, there were
      2435 treatment failures (5.9%) and 5436 recurrences (18.2%). The adjusted odds
      ratios for treatment failure were 1.67 (95% CI: 1.44-1.95) for trimethoprim
      sulfamethoxazole and 1.22 (95% CI: 1.06-1.41) for beta-lactams; the adjusted
      hazard ratios for recurrence were 1.30 (95% CI: 1.18-1.44) for trimethoprim
      sulfamethoxazole and 1.08 (95% CI: 0.99-1.18) for beta-lactams. CONCLUSIONS:
      Compared with clindamycin, use of trimethoprim-sulfamethoxazole or beta-lactams
      was associated with increased risks of treatment failure and recurrence.
      Associations were stronger for those with a drainage procedure.

PMID- 21844059
TI  - Use of a pressure guidewire in fetal cardiac intervention for critical aortic
      stenosis.
AB  - Fetal cardiac intervention for critical aortic stenosis (AS) with evolving
      hypoplastic left heart syndrome is performed in an attempt to maintain a
      biventricular circulation postnatally. The procedure has been hindered by
      technical challenges and poor candidate selection. We report here the novel use
      of a pressure guidewire during aortic valvuloplasty in a fetus at 21 weeks'
      gestation with critical AS and evolving hypoplastic left heart syndrome. Use of a
      pressure guidewire during fetal cardiac intervention offers several potential
      advantages over existing protocols. This technique augments fetal ultrasound as
      it relates to operator awareness of catheter and wire position (with continuous
      monitoring of pressure waveforms), improves on intraprocedural fetal hemodynamic
      monitoring and responsiveness to resuscitation, and provides a rich new data set
      of invasive fetal hemodynamics. This data set offers tremendous potential with
      regards to improving candidate selection and postintervention prognostication. In
      addition, we provide the first, to our knowledge, characterization of
      intracardiac pressures in a human fetus with congenital heart disease. Given the
      realized and potential benefits associated with this technique, use of a pressure
      guidewire may become standard of care for all fetal cardiac interventions.

PMID- 21844060
TI  - Anogenital human papillomavirus in sexually abused and nonabused children: a
      multicenter study.
AB  - OBJECTIVES: To characterize the epidemiology of genital human papillomavirus
      (HPV) infection in children without previous consensual sexual activity,
      comparing HPV prevalence by certainty of child sexual abuse (CSA). PATIENTS AND
      METHODS: Patients presenting for evaluation of CSA in 8 sites in Atlanta,
      Houston, Harrisburg, and New York City were recruited along with patients
      presenting for unrelated health visits. CSA certainty was classified as definite,
      probable, possible, or no evidence following published guidelines and the results
      of history, physical examination, and laboratory tests. Urine and swabs of
      external genitalia were tested for HPV using L1 consensus polymerase chain
      reaction. RESULTS: The study included 576 participants (89.9% female) aged 6
      months to 13 years (mean: 7.9); 534 of whom were evaluated for CSA and 42 for
      unrelated reasons. Of those evaluated for CSA, 14 had genital warts. One or more
      HPV types were detected in 11.8% (61 of 517) of participants with adequate
      samples. HPV detection was more likely among abused participants (definite,
      probable, or possible) than among participants without evidence of CSA (13.7% and
      1.3%, respectively; P < .0001) and increased with certainty of abuse (8.4%,
      15.6%, and 14.5% in participants with possible, probable, and definite CSA,
      respectively; P < .0001). Participants aged 10 years or older had a higher
      prevalence of HPV (20.6%) than others (5.6%) (P < .0001). CSA, anogenital warts,
      and age were independently associated with HPV detection. CONCLUSIONS: HPV
      detection was associated with CSA and increased with CSA certainty. In this
      population, genital HPV seemed to behave as a sexually transmitted infection.

PMID- 21844061
TI  - Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates
      renal scarring.
AB  - OBJECTIVE: To determine if glucocorticoids can prevent renal scar formation after
      acute pyelonephritis in pediatric patients. METHODS: Patients younger than 16
      years diagnosed with their first episode of acute pyelonephritis with a high risk
      of renal scar formation (ie, inflammatory volume >= 4.6 mL on technetium-99m
      labeled dimercaptosuccinic acid scan [DMSA] or abnormal renal ultrasonography
      results) were randomly assigned to receive either antibiotics plus
      methylprednisolone sodium phosphate (1.6 mg/kg per day for 3 days [MPD group]) or
      antibiotics plus placebo (placebo group) every 6 hours for 3 days. Patients were
      reassessed by using DMSA 6 months after treatment. The primary outcome was the
      development of renal scars. RESULTS: A total of 84 patients were enrolled: 19 in
      the MPD group and 65 in the placebo group. Patient characteristics were similar
      between the 2 groups, including the acute inflammatory parameters and the initial
      DMSA result. Renal scarring was found in 33.3% of children treated with MPD and
      in 60.0% of those who received placebo (P < .05). The median cortical defect
      volumes on follow-up DMSA were 0.0 mL (range: 0-4.5 mL) and 1.5 mL (range: 0-14.8
      mL) for the MPD and placebo groups, respectively (P < .01). Patients in the MPD
      group experienced faster defervescence after treatment than the placebo group.
      CONCLUSIONS: Adjunctive oral MPD therapy reduced the occurrence and/or severity
      of renal scarring after acute pyelonephritis in these hospitalized children who
      had a high risk of renal scar formation.

PMID- 21844062
TI  - Publishing quality reports: spreading research and innovation.

PMID- 21844063
TI  - Qualitative comparison of blackcurrant and blackcurrant--whey beverages.
AB  - This study provides a qualitative comparison of blackcurrant and blackcurrant
      whey beverages over a 12-month storage period. The amount of extract in the
      beverages was established as 12%, of which 25% was blackcurrant concentrate. Acid
      whey was used for the production of blackcurrant-whey beverages. In comparison to
      blackcurrant-whey beverages, blackcurrant beverages contained significantly more
      glucose, fructose, sucrose, polyphenols and vitamins C and B1. They also had a
      higher level of antioxidant activity against ABTS*+ and DPPH, with the difference
      ranging from 2% to 46%. On the other hand, blackcurrant-whey beverages contained
      more ash, proteins and vitamin B2 and the presence of lactose was detected. They
      were also characterized by higher color parameter values evaluated according to
      the CIE system. A general sensory evaluation awarded blackcurrant beverages with
      0.5-1.3 more points than blackcurrant-whey beverages. A descriptive flavor
      analysis found that blackcurrant taste dominated in both types of beverages;
      however, in blackcurrant-whey beverages, the taste and smell of whey were also
      discernible. Changes in the quality of the beverages were observed during the
      storage period, notably a decrease in their antioxidant properties.

PMID- 21844064
TI  - Fatigue and its relationships with cognitive functioning and depression in
      paediatric multiple sclerosis.
AB  - BACKGROUND: There is limited information on fatigue and its clinical and
      psychosocial correlates in children and adolescents with multiple sclerosis (MS).
      OBJECTIVE: To assess the relationships between fatigue, cognitive functioning and
      depression in paediatric MS. METHODS: The study cohort consisted of patients with
      MS recruited for an Italian collaborative study on cognitive and psychosocial
      functioning in paediatric MS. The present assessment included evaluation of
      fatigue on the Pediatric Quality of Life Inventory-Multidimensional Fatigue
      Scale, cognitive functioning on an extensive neuropsychological battery and
      depression on the Children's Depression Inventory (CDI). A psychiatric interview
      through the Kiddie-SADS-Present and Lifetime Version was also administered.
      RESULTS: In total, 57 patients with relapsing-remitting MS were compared with 70
      healthy controls. Percentages of fatigued patients ranged from 9% to 14%
      according to self-reports, and from 23% to 39% according to parent reports.
      Fatigue was significantly related with higher scores on the CDI (p < 0.03).
      Higher levels of self-reported cognitive fatigue were associated with impaired
      performance on a problem-solving test, whereas higher levels of parent-reported
      cognitive fatigue were associated with impairment on tests of verbal learning,
      processing speed, complex attention and verbal comprehension. CONCLUSIONS: Our
      data show that fatigue can affect a sizeable proportion of paediatric MS
      patients, and confirm the association between fatigue and depressive symptoms in
      MS. They also highlight the difficulties of fatigue assessment in the paediatric
      population and provide a few clues to further research in the field.

PMID- 21844065
TI  - No increase in cancer incidence detected after cyclophosphamide in a French
      cohort of patients with progressive multiple sclerosis.
AB  - BACKGROUND: Cyclophosphamide is still used in progressive forms of multiple
      sclerosis (MS) in view of its suggested efficacy and safety in the short term. No
      data exist on its long-term safety in MS, particularly on the risk of malignancy.
      OBJECTIVE: The objective of this study was to evaluate cancer incidence in MS
      after cyclophosphamide treatment. METHODS: We performed a historical prospective
      study in a cohort of MS patients treated with cyclophosphamide. We collected
      demographic data and medical history from medical databases and patient
      interviews. Reported cancers were histologically confirmed. Cancer incidence was
      compared with the incidence in the general population by estimating standardized
      incidence ratios (SIRs). RESULTS: We included 354 patients, with a median follow
      up of 5 years (range 2-15) after cyclophosphamide treatment. Fifteen patients
      developed a solid cancer, which occurred at a median of 3 years (range 0.5-14)
      after cyclophosphamide introduction. The cumulative incidence of cancer after
      cyclophosphamide was 3.1% at 5 years and 5.9% at 8 years. We found no increase in
      cancer incidence after cyclophosphamide treatment in men (SIR = 0.83, 95%
      confidence interval [CI] 0.30-1.82), women (SIR = 0.99, 95% CI 0.43-1.95), or men
      and women combined (SIR = 0.92, 95% CI 0.50-1.54). CONCLUSION: We found no
      evidence of an increased risk of cancer associated with cyclophosphamide
      treatment in MS patients.

PMID- 21844066
TI  - Serum from interferon-beta-1b-treated patients with early multiple sclerosis
      stabilizes the blood-brain barrier in vitro.
AB  - Interferon-beta (IFN-beta) stabilizes the blood-brain barrier (BBB) in vitro.
      Here we investigated the effect of serum from 15 IFN-beta-1b-treated multiple
      sclerosis (MS) patients on the permeability read-outs of small solutes in an in
      vitro BBB model consisting of human brain microvascular endothelial cells in co
      culture with rat astrocytes. The addition of sera from IFN-beta-treated patients
      resulted in a significantly (p < 0.05) reduced permeability as compared with
      untreated patients. Our findings show that sera from IFN-beta-1b-treated MS
      patients have a stabilizing effect on the in vitro BBB. We suggest an unknown
      potentially pro-inflammatory factor in the serum of MS patients that may lead to
      a BBB dysfunction and can be modulated by IFN-beta.

PMID- 21844067
TI  - Substantial adverse association of visual and vascular comorbidities on visual
      disability in multiple sclerosis.
AB  - BACKGROUND: Visual comorbidities are common in multiple sclerosis (MS) but the
      impact of visual comorbidities on visual disability is unknown. OBJECTIVE: We
      assessed the impact of visual and vascular comorbidities on severity of visual
      disability in MS. METHODS: In 2006, we queried participants of the North American
      Research Committee on Multiple Sclerosis (NARCOMS) about cataracts, glaucoma,
      uveitis, hypertension, hypercholesterolemia, heart disease, diabetes and
      peripheral vascular disease. We assessed visual disability using the Vision
      subscale of Performance Scales. Using Cox regression, we investigated whether
      visual or vascular comorbidities affected the time between MS symptom onset and
      the development of mild, moderate and severe visual disability. RESULTS: Of 8983
      respondents, 1415 (15.9%) reported a visual comorbidity while 4745 (52.8%)
      reported a vascular comorbidity. The median (interquartile range) visual score
      was 1 (0-2). In a multivariable Cox model the risk of mild visual disability was
      higher among participants with vascular (hazard ratio [HR] 1.45; 95% confidence
      interval [CI]: 1.39-1.51) and visual comorbidities (HR 1.47; 95% CI: 1.37-1.59).
      Vascular and visual comorbidities were similarly associated with increased risks
      of moderate and severe visual disability. CONCLUSIONS: Visual and vascular
      comorbidities are associated with progression of visual disability in MS.
      Clinicians hearing reports of worsening visual symptoms in MS patients should
      consider visual comorbidities as contributing factors. Further study of these
      issues using objective, systematic neuro-ophthalmologic evaluations is warranted.

PMID- 21844069
TI  - Images in vascular medicine. The persistent left superior vena cava draining into
      the left atrium via the left superior pulmonary vein.

PMID- 21844068
TI  - Giant syphilitic aortic aneurysm: a case report and review of the literature.
AB  - Thoracic aortic aneurysm formation is a known complication of late syphilis.
      Large aneurysms may cause symptoms via mass effect. When aneurysms compress the
      pulmonary artery, pulmonary arterial hypertension and right heart failure may
      result. We report the case of a 76-year-old man who presented with right heart
      failure secondary to an 11-cm syphilitic thoracic aortic aneurysm, and discuss
      the evolving epidemiology, complications, diagnosis and management of syphilitic
      aortitis.

PMID- 21844070
TI  - Images in vascular medicine: aortic intramural hematoma with dissection in aortic
      medial degeneration.

PMID- 21844071
TI  - Evaluation of effects of eicosapentaenoic acid on Na+-K+-ATPase in sheep
      pulmonary artery.
AB  - In the present study, we have evaluated the effects of eicosapentaenoic acid
      (EPA) on Na(+)-K(+)-ATPase in sheep pulmonary artery. Acute (30 min) and
      prolonged (24 h) exposure of arterial rings to EPA (30 MUM) significantly
      decreased potassium chloride (KCl)-induced relaxation, an index of functional
      Na(+)-K(+)-ATPase activity. In acute exposure, the pD(2) and E (max) (the maximal
      response) values for KCl-induced relaxation were 3.21 +/- 0.33 and 61.58 +/-
      11.30% (n = 5) versus control 3.58 +/- 0.07 and 82.44 +/- 2.36% (n = 24),
      respectively. The pD(2) and E (max) values for KCl-induced relaxation in arterial
      rings exposed to EPA for 24 h in organ culture were 2.52 +/- 0.11 and 55.00 +/-
      5.72% versus control 3.04 +/- 0.19 and 80.74 +/- 11.96%, respectively; n = 4.
      Exposure of the arterial rings to EPA (30 MUM) for 24 h in organ culture,
      significantly decreased (17.58 +/- 2.15%) the protein expression of alpha(1)
      isoform of Na(+)-K(+)-ATPase. Acute exposure to EPA for 30 min significantly
      decreased (21.06 +/- 5.89%) the Na(+)-K(+)-ATPase activity as measured by
      inorganic phosphate (Pi) release. EPA, up to 100 MUM concentration, marginally
      (<10% of 80 mM KCl contraction) increased the basal tone of the pulmonary artery.
      Additionally, EPA (10-30 MUM) had no effect on Mg(2+)-ATPase activity as well as
      on cyclic guanosine monophosphate (cGMP) production. All these results show that
      EPA has inhibitory effect on Na(+)-K(+)-ATPase in sheep pulmonary artery but
      prolonged exposure had no additional effect on sodium pump, and EPA-induced
      inhibition of Na(+)-K(+)-ATPase may be due to attenuation in protein expression
      of alpha(1) isoform of Na(+)-K(+)-ATPase independent of cGMP production.

PMID- 21844072
TI  - ACCF/AHA 2011 health policy statement on therapeutic interchange and
      substitution: a report of the American College of Cardiology Foundation Clinical
      Quality Committee.

PMID- 21844073
TI  - Diabetes mellitus worsens diastolic left ventricular dysfunction in aortic
      stenosis through altered myocardial structure and cardiomyocyte stiffness.
AB  - BACKGROUND: Aortic stenosis (AS) and diabetes mellitus (DM) are frequent
      comorbidities in aging populations. In heart failure, DM worsens diastolic left
      ventricular (LV) dysfunction, thereby adversely affecting symptoms and prognosis.
      Effects of DM on diastolic LV function were therefore assessed in aortic
      stenosis, and underlying myocardial mechanisms were identified. METHODS AND
      RESULTS: Patients referred for aortic valve replacement were subdivided into
      patients with AS and no DM (AS; n=46) and patients with AS and DM (AS-DM; n=16).
      Preoperative Doppler echocardiography and hemodynamics were implemented with
      perioperative LV biopsies. Histomorphometry and immunohistochemistry quantified
      myocardial collagen volume fraction and myocardial advanced glycation end product
      deposition. Isolated cardiomyocytes were stretched to 2.2-MUm sarcomere length to
      measure resting tension (F(passive)). Expression and phosphorylation of titin
      isoforms were analyzed with gel electrophoresis with ProQ Diamond and SYPRO Ruby
      stains. Reduced LV end-diastolic distensibility in AS-DM was evident from higher
      LV end-diastolic pressure (21+/-1 mm Hg for AS versus 28+/-4 mm Hg for AS-DM;
      P=0.04) at comparable LV end-diastolic volume index and attributed to higher
      myocardial collagen volume fraction (AS, 12.9+/-1.1% versus AS-DM, 18.2+/-2.6%;
      P<0.001), more advanced glycation end product deposition in arterioles, venules,
      and capillaries (AS, 14.4+/-2.1 score per 1 mm(2) versus AS-DM, 31.4+/-6.1 score
      per 1 mm2; P=0.03), and higher F(passive) (AS, 3.5+/-1.7 kN/m2 versus AS-DM,
      5.1+/-0.7 kN/m2; P=0.04). Significant hypophosphorylation of the stiff N2B titin
      isoform in AS-DM explained the higher F(passive) and normalization of F(passive)
      after in vitro treatment with protein kinase A. CONCLUSIONS: Worse diastolic LV
      dysfunction in AS-DM predisposes to heart failure and results from more
      myocardial fibrosis, more intramyocardial vascular advanced glycation end product
      deposition, and higher cardiomyocyte F(passive), which was related to
      hypophosphorylation of the N2B titin isoform.

PMID- 21844074
TI  - Donor simvastatin treatment abolishes rat cardiac allograft ischemia/reperfusion
      injury and chronic rejection through microvascular protection.
AB  - BACKGROUND: Ischemia/reperfusion injury may have deleterious short- and long-term
      consequences for cardiac allografts. The underlying mechanisms involve
      microvascular dysfunction that may culminate in primary graft failure or
      untreatable chronic rejection. METHODS AND RESULTS: Here, we report that rat
      cardiac allograft ischemia/reperfusion injury resulted in profound microvascular
      dysfunction that was prevented by donor treatment with peroral single-dose
      simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase and Rho GTPase
      inhibitor, 2 hours before graft procurement. During allograft preservation, donor
      simvastatin treatment inhibited microvascular endothelial cell and pericyte
      RhoA/Rho-associated protein kinase activation and endothelial cell-endothelial
      cell gap formation; decreased intragraft mRNA levels of hypoxia-inducible factor
      1alpha, inducible nitric oxide synthase, and endothelin-1; and increased heme
      oxygenase-1. Donor, but not recipient, simvastatin treatment prevented
      ischemia/reperfusion injury-induced vascular leakage, leukocyte infiltration, the
      no-reflow phenomenon, and myocardial injury. The beneficial effects of
      simvastatin on vascular stability and the no-reflow phenomenon were abolished by
      concomitant nitric oxide synthase inhibition with N-nitro-l-arginine methyl ester
      and RhoA activation by geranylgeranyl pyrophosphate supplementation,
      respectively. In the chronic rejection model, donor simvastatin treatment
      inhibited cardiac allograft inflammation, transforming growth factor-beta1
      signaling, and myocardial fibrosis. In vitro, simvastatin inhibited transforming
      growth factor-beta1-induced microvascular endothelial-to-mesenchymal transition.
      CONCLUSIONS: Our results demonstrate that donor simvastatin treatment prevents
      microvascular endothelial cell and pericyte dysfunction, ischemia/reperfusion
      injury, and chronic rejection and suggest a novel, clinically feasible strategy
      to protect cardiac allografts.

PMID- 21844075
TI  - Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II):
      RenalGuard System in high-risk patients for contrast-induced acute kidney injury.
AB  - BACKGROUND: The RenalGuard System, which creates high urine output and fluid
      balancing, may be beneficial in preventing contrast-induced acute kidney injury.
      METHODS AND RESULTS: The Renal Insufficiency After Contrast Media Administration
      Trial II (REMEDIAL II) trial is a randomized, multicenter, investigator-driven
      trial addressing the prevention of contrast-induced acute kidney injury in high
      risk patients. Patients with an estimated glomerular filtration rate <=30 mL .
      min(-1) . 1.73 m(-2) and/or a risk score >=11 were randomly assigned to sodium
      bicarbonate solution and N-acetylcysteine (control group) or hydration with
      saline and N-acetylcysteine controlled by the RenalGuard System and furosemide
      (RenalGuard group). The primary end point was an increase of >=0.3 mg/dL in the
      serum creatinine concentration at 48 hours after the procedure. The secondary end
      points included serum cystatin C kinetics and rate of in-hospital dialysis.
      Contrast-induced acute kidney injury occurred in 16 of 146 patients in the
      RenalGuard group (11%) and in 30 of 146 patients in the control group (20.5%;
      odds ratio, 0.47; 95% confidence interval, 0.24 to 0.92). There were 142 patients
      (48.5%) with an estimated glomerular filtration rate <=30 mL . min(-1) . 1.73 and
      149 patients (51.5%) with only a risk score >=11. Subgroup analysis according to
      inclusion criteria showed a similarly lower risk of adverse events (estimated
      glomerular filtration rate <=30 mL . min(-1) . 1.73 m(-2): odds ratio, 0.44; risk
      score >=11: odds ratio, 0.45; P for interaction=0.97). Changes in cystatin C at
      24 hours (0.02+/-0.32 versus -0.08+/-0.26; P=0.002) and 48 hours (0.12+/-0.42
      versus 0.03+/-0.31; P=0.001) and the rate of in-hospital dialysis (4.1% versus
      0.7%; P=0.056) were higher in the control group. CONCLUSION: RenalGuard therapy
      is superior to sodium bicarbonate and N-acetylcysteine in preventing contrast
      induced acute kidney injury in high-risk patients. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrial.gov. Unique identifier: NCT01098032.

PMID- 21844076
TI  - Atrial sources of reactive oxygen species vary with the duration and substrate of
      atrial fibrillation: implications for the antiarrhythmic effect of statins.
AB  - BACKGROUND: An altered nitric oxide-redox balance has been implicated in the
      pathogenesis of atrial fibrillation (AF). Statins inhibit NOX2-NADPH oxidases and
      prevent postoperative AF but are less effective in AF secondary prevention; the
      mechanisms underlying these findings are poorly understood. METHODS AND RESULTS:
      By using goat models of pacing-induced AF or of atrial structural remodeling
      secondary to atrioventricular block and right atrial samples from 130 patients
      undergoing cardiac surgery, we found that the mechanisms responsible for the NO
      redox imbalance differ between atria and with the duration and substrate of AF.
      Rac1 and NADPH oxidase activity and the protein level of NOX2 and p22phox were
      significantly increased in the left atrium of goats after 2 weeks of AF and in
      patients who developed postoperative AF in the absence of differences in
      leukocytes infiltration. Conversely, in the presence of longstanding AF or
      atrioventricular block, uncoupled nitric oxide synthase activity (secondary to
      reduced BH4 content and/or increased arginase activity) and mitochondrial
      oxidases accounted for the biatrial increase in reactive oxygen species.
      Atorvastatin caused a mevalonate-reversible inhibition of Rac1 and NOX2-NADPH
      oxidase activity in right atrial samples from patients who developed
      postoperative AF, but it did not affect reactive oxygen species, nitric oxide
      synthase uncoupling, or BH4 in patients with permanent AF. CONCLUSIONS:
      Upregulation of atrial NADPH oxidases is an early but transient event in the
      natural history of AF. Changes in the sources of reactive oxygen species with
      atrial remodeling may explain why statins are effective in the primary prevention
      of AF but not in its management.

PMID- 21844077
TI  - Risk of constrictive pericarditis after acute pericarditis.
AB  - BACKGROUND: Constrictive pericarditis (CP) is considered a rare, dreaded possible
      complication of acute pericarditis. Nevertheless, there is a lack of prospective
      studies that have evaluated the specific risk according to different etiologies.
      The aim of this study is to evaluate the risk of CP after acute pericarditis in a
      prospective cohort study with long-term follow-up. METHODS AND RESULTS: From
      January 2000 to December 2008, 500 consecutive cases with a first episode of
      acute pericarditis (age, 51+/-16 years; 270 men) were prospectively studied to
      evaluate the evolution toward CP. Etiologies were viral/idiopathic in 416 cases
      (83.2%), connective tissue disease/pericardial injury syndromes in 36 cases
      (7.2%), neoplastic pericarditis in 25 cases (5.0%), tuberculosis in 20 cases
      (4.0%), and purulent in 3 cases (0.6%). During a median follow-up of 72 months
      (range, 24 to 120 months), CP developed in 9 of 500 patients (1.8%): 2 of 416
      patients with idiopathic/viral pericarditis (0.48%) versus 7 of 84 patients with
      a nonviral/nonidiopathic etiology (8.3%). The incidence rate of CP was 0.76 cases
      per 1000 person-years for idiopathic/viral pericarditis, 4.40 cases per 1000
      person-years for connective tissue disease/pericardial injury syndrome, 6.33
      cases per 1000 person-years for neoplastic pericarditis, 31.65 cases for 1000
      person-years for tuberculous pericarditis, and 52.74 cases per 1000 person-years
      for purulent pericarditis. CONCLUSIONS: CP is a relatively rare complication of
      viral or idiopathic acute pericarditis (<0.5%) but, in contrast, is relatively
      frequent for specific etiologies, especially bacterial.

PMID- 21844078
TI  - Role of perivascular adipose tissue-derived methyl palmitate in vascular tone
      regulation and pathogenesis of hypertension.
AB  - BACKGROUND: Perivascular adipose tissue (PVAT)-derived relaxing factor (PVATRF)
      significantly regulates vascular tone. Its chemical nature remains unknown. We
      determined whether palmitic acid methyl ester (PAME) was the PVATRF and whether
      its release and/or vasorelaxing activity decreased in hypertension. METHODS AND
      RESULTS: Using superfusion bioassay cascade technique, tissue bath myography, and
      gas chromatography/mass spectrometry, we determined PVATRF and PAME release from
      aortic PVAT preparations of Wistar Kyoto rats and spontaneously hypertensive
      rats. The PVAT of Wistar Kyoto rats spontaneously and calcium dependently
      released PVATRF and PAME. Both induced aortic vasorelaxations, which were
      inhibited by 4-aminopyridine (2 mmol/L) and tetraethylammonium 5 and 10 mmol/L
      but were not affected by tetraethylammonium 1 or 3 mmol/L, glibenclamide (3
      MUmol/L), or iberiotoxin (100 nmol/L). Aortic vasorelaxations induced by PVATRF-
      and PAME-containing Krebs solutions were not affected after heating at 70 degrees
      C but were equally attenuated after hexane extractions. Culture mediums of
      differentiated adipocytes, but not those of fibroblasts, contained significant
      PAME and caused aortic vasorelaxation. The PVAT of spontaneously hypertensive
      rats released significantly less PVATRF and PAME with an increased release of
      angiotensin II. In addition, PAME-induced relaxation of spontaneously
      hypertensive rats aortic smooth muscle diminished drastically, which was
      ameliorated significantly by losartan. CONCLUSIONS: We found that PAME is the
      PVATRF, causing vasorelaxation by opening voltage-dependent K+ channels on smooth
      muscle cells. Diminished PAME release and its vasorelaxing activity and increased
      release of angiotensin II in the PVAT suggest a noble role of PVAT in
      pathogenesis of hypertension. The antihypertensive effect of losartan is
      attributed partly to its reversing diminished PAME-induced vasorelaxation.

PMID- 21844079
TI  - Low prevalence of abdominal aortic aneurysm among 65-year-old Swedish men
      indicates a change in the epidemiology of the disease.
AB  - BACKGROUND: Screening elderly men with ultrasound is an established method to
      reduce mortality from ruptured abdominal aortic aneurysm (AAA; Evidence Level
      1a). Such programs are being implemented and generally consist of a single scan
      at 65 years of age. We report the results from screening 65-year-old men for AAA
      in middle Sweden. METHODS AND RESULTS: All 65-year-old men (n=26,256), identified
      through the National Population Registry, were invited to an ultrasound
      examination. An AAA was defined as a maximum infrarenal aortic diameter of >=30
      mm. In total, 22 187 (85%) accepted, and 373 AAAs were detected (1.7%; 95%
      confidence interval, 1.5 to 1.9). With 127 previously known AAAs (repaired/under
      surveillance) included, the total prevalence of the disease in the population was
      2.2% (95% confidence interval, 2.0 to 2.4). Self-reported smoking (odds ratio,
      3.4; P<0.001), coronary artery disease (odds ratio, 2.0; P<0.001), and
      hypertension (odds ratio, 1.6; P=0.001) were independently associated with AAA in
      a multivariate logistic regression model. Thirteen percent of the entire
      population reported to be current smokers, one third of the frequency reported in
      the 1980s. The observed low prevalence of AAA was explained mainly by this change
      in smoking habits. CONCLUSIONS: On the basis of the observed reduced exposure to
      risk factors, lower-than-expected prevalence of AAA among 65-year-old men,
      unchanged AAA repair rate, and significantly improved longevity of the elderly
      population, the current generally agreed-on AAA screening model can be
      questioned. Important issues to address are the threshold diameter for follow-up,
      the possible need for rescreening at a higher age, and selective screening among
      smokers.

PMID- 21844081
TI  - Clinical and economic outcomes of liberal versus selective drug-eluting stent
      use: insights from temporal analysis of the multicenter Evaluation of Drug
      Eluting Stents and Ischemic Events (EVENT) registry.
AB  - BACKGROUND: Although the benefits of drug-eluting stents (DES) for reducing
      restenosis after percutaneous coronary intervention are well established, the
      impact of alternative rates of DES use on population-level outcomes is unknown.
      METHODS AND RESULTS: We used data from the Evaluation of Drug Eluting Stents and
      Ischemic Events (EVENT) registry to examine the clinical impact and cost
      effectiveness of varying DES use rates in routine care. Between 2004 and 2007,
      10,144 patients undergoing percutaneous coronary intervention were enrolled in
      the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular
      specific costs were assessed prospectively over 1 year of follow-up. Use of DES
      decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007
      (selective use era; n=2557; P<0.001). One-year rates of death or myocardial
      infarction were similar in both eras. Over this time period, the incidence of
      target lesion revascularization increased from 4.1 to 5.1, an absolute increase
      of 1.0 (95 confidence interval, 0.1 to 1.9; P=0.03), whereas total cardiovascular
      costs per patient decreased by $401 (95 confidence interval, 131 to 671;
      P=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal
      versus selective DES era was $16,000 per target lesion revascularization event
      avoided, $27,000 per repeat revascularization avoided, and $433 000 per quality
      adjusted life-year gained. CONCLUSIONS: In this prospective registry, a temporal
      reduction in DES use was associated with a small increase in target lesion
      revascularization and a modest reduction in total cardiovascular costs. These
      findings suggest that although clinical outcomes are marginally better with
      unrestricted DES use, this approach represents a relatively inefficient use of
      healthcare resources relative to several common benchmarks for cost-effective
      care.

PMID- 21844080
TI  - Comparative effectiveness of exercise electrocardiography with or without
      myocardial perfusion single photon emission computed tomography in women with
      suspected coronary artery disease: results from the What Is the Optimal Method
      for Ischemia Evaluation in Women (WOMEN) trial.
AB  - BACKGROUND: There is a paucity of randomized trials regarding diagnostic testing
      in women with suspected coronary artery disease (CAD). It remains unclear whether
      the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise
      treadmill test (ETT) provides incremental information to improve clinical
      decision making in women with suspected CAD. METHODS AND RESULTS: We randomized
      symptomatic women with suspected CAD, an interpretable ECG, and >=5 metabolic
      equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies:
      ETT or exercise MPI. The primary end point was 2-year incidence of major adverse
      cardiac events, defined as CAD death or hospitalization for an acute coronary
      syndrome or heart failure. A total of 824 women were randomized to ETT or
      exercise MPI. For women randomized to ETT, ECG results were normal in 64%,
      indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI
      results were normal in 91%, mildly abnormal in 3%, and moderate to severely
      abnormal in 6%. At 2 years, there was no difference in major adverse cardiac
      events (98.0% for ETT and 97.7% for MPI; P=0.59). Compared with ETT, index
      testing costs were higher for exercise MPI (P<0.001), whereas downstream
      procedural costs were slightly lower (P=0.0008). Overall, the cumulative
      diagnostic cost savings was 48% for ETT compared with exercise MPI (P<0.001).
      CONCLUSIONS: In low-risk, exercising women, a diagnostic strategy that uses ETT
      versus exercise MPI yields similar 2-year posttest outcomes while providing
      significant diagnostic cost savings. The ETT with selective follow-up testing
      should be considered as the initial diagnostic strategy in symptomatic women with
      suspected CAD. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique
      identifier: NCT00282711.

PMID- 21844082
TI  - n-3 polyunsaturated fatty acids in the prevention of atrial fibrillation
      recurrences after electrical cardioversion: a prospective, randomized study.
AB  - BACKGROUND: n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic
      effects and reduce sudden cardiac death. However, their role in the prevention of
      atrial fibrillation remains controversial. We aimed to determine the effect of n
      3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system
      inhibitor on the maintenance of sinus rhythm after direct current cardioversion
      in patients with persistent atrial fibrillation. METHODS AND RESULTS: We
      conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in
      patients with persistent atrial fibrillation, with at least 1 relapse after
      cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone
      system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and
      then underwent direct current cardioversion 4 weeks later. The primary end point
      was the probability of maintenance of sinus rhythm at 1 year after cardioversion.
      Of 254 screened patients, 199 were found to be eligible and randomized. At the 1
      year follow up, the probability of maintenance of sinus rhythm was significantly
      higher in the n-3 PUFAs-treated patients compared with the placebo group (hazard
      ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence
      interval, 0.26 to 0.46], respectively; P=0.0001). CONCLUSIONS: In patients with
      persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone
      system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the
      maintenance of sinus rhythm after direct current cardioversion. Our data suggest
      that n-3 PUFAs may exert beneficial effects in the prevention of atrial
      fibrillation recurrence. Further studies are needed to confirm and expand our
      findings. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01198275.

PMID- 21844083
TI  - Ventricular assist device-associated thrombus.

PMID- 21844085
TI  - Letter by Ranucci et al regarding article, "Comparison between transcatheter and
      surgical prosthetic valve implantation in patients with severe aortic stenosis
      and reduced left ventricular ejection fraction".

PMID- 21844086
TI  - Letter by Subramanian et al regarding article, "Comparison between transcatheter
      and surgical prosthetic valve implantation in patients with severe aortic
      stenosis and reduced left ventricular ejection fraction".

PMID- 21844087
TI  - In vivo assessment of the risk profile of evolving individual coronary plaques: a
      step closer.

PMID- 21844088
TI  - Socking It to cardiac hypertrophy: STIM1-mediated Ca2+ entry in the
      cardiomyocyte.

PMID- 21844089
TI  - Bleeding in very old patients on vitamin K antagonist therapy.

PMID- 21844090
TI  - Prevention of overweight/obesity as a strategy to optimize cardiovascular health.

PMID- 21844091
TI  - The need for regional integrated care for ST-segment elevation myocardial
      infarction.

PMID- 21844092
TI  - Still a kid at heart: hypertrophic cardiomyopathy in the elderly.

PMID- 21844093
TI  - Recurrent left ventricular myocardial infarction: tissue characterization with
      cardiac magnetic resonance imaging.

PMID- 21844094
TI  - Feeling threatened about the future: Whites' emotional reactions to anticipated
      ethnic demographic changes.
AB  - In many Western countries, the proportion of the population that is White will
      drop below 50% within the next century. Two experiments examined how anticipation
      of these future ethnic demographics affects current intergroup processes. In
      Study 1, White Americans who viewed actual demographic projections for a time
      when Whites are no longer a numerical majority felt more angry toward and fearful
      of ethnic minorities than Whites who did not view future projections. Whites who
      viewed the future projections also felt more sympathy for their ingroup than
      Whites in the control condition. In Study 2, the authors replicated the effects
      for intergroup emotions with a sample of White Canadians. White Canadians who
      thought about a future in which Whites were a numerical minority appraised the
      ingroup as more threatened, which mediated the effect of condition on intergroup
      emotions. The authors discuss the implications of these findings for race
      relations in increasingly diverse societies.

PMID- 21844095
TI  - On boredom and social identity: a pragmatic meaning-regulation approach.
AB  - People who feel bored experience that their current situation is meaningless and
      are motivated to reestablish a sense of meaningfulness. Building on the
      literature that conceptualizes social identification as source of meaningfulness,
      the authors tested the hypothesis that boredom increases the valuation of
      ingroups and devaluation of outgroups. Indeed, state boredom increased the liking
      of an ingroup name (Study 1), it increased hypothetical jail sentences given to
      an outgroup offender (Study 2 and Study 3), especially in comparison to an
      ingroup offender (Study 3), it increased positive evaluations of participants'
      ingroups, especially when ingroups were not the most favored ones to begin with
      (Study 4), and it increased the appreciation of an ingroup symbol, mediated by
      people's need to engage in meaningful behavior (Study 5). Several measures ruled
      out that these results could be explained by other affective states. These novel
      findings are discussed with respect to boredom, social identity, and existential
      psychology research.

PMID- 21844096
TI  - Culture of honor and violence against the self.
AB  - Cultures of honor facilitate certain forms of interpersonal violence. The authors
      suggest that these cultures might also promote values and expectations that could
      heighten suicide risk, such as strict gender-role standards and hypersensitivity
      to reputational threats, which could lead people living in such cultures to
      consider death as an option when failure occurs or reputation is threatened
      sufficiently. Study 1 shows that, controlling for a host of statewide covariates,
      honor states in the United States have significantly higher male and female
      suicide rates than do nonhonor states, particularly in nonmetropolitan areas
      among Whites. Study 2 shows that statewide levels of antidepressant prescriptions
      (an indicator of mental health resource utilization) are lower in honor states,
      whereas levels of major depression are higher, and statewide levels of depression
      are associated with suicide rates only among honor states. Finally, Study 3 shows
      that individual endorsement of honor ideology is positively associated with
      depression.

PMID- 21844097
TI  - Vascular dysfunction in experimental diabetes is improved by pentaerithrityl
      tetranitrate but not isosorbide-5-mononitrate therapy.
AB  - OBJECTIVE: Diabetes is associated with vascular oxidative stress, activation of
      NADPH oxidase, and uncoupling of nitric oxide (NO) synthase (endothelial NO
      synthase [eNOS]). Pentaerithrityl tetranitrate (PETN) is an organic nitrate with
      potent antioxidant properties via induction of heme oxygenase-1 (HO-1). We tested
      whether treatment with PETN improves vascular dysfunction in the setting of
      experimental diabetes. RESEARCH DESIGN AND METHODS: After induction of
      hyperglycemia by streptozotocin (STZ) injection (60 mg/kg i.v.), PETN (15
      mg/kg/day p.o.) or isosorbide-5-mononitrate (ISMN; 75 mg/kg/day p.o.) was fed to
      Wistar rats for 7 weeks. Oxidative stress was assessed by optical methods and
      oxidative protein modifications, vascular function was determined by isometric
      tension recordings, protein expression was measured by Western blotting, RNA
      expression was assessed by quantitative RT-PCR, and HO-1 promoter activity in
      stable transfected cells was determined by luciferase assays. RESULTS: PETN, but
      not ISMN, improved endothelial dysfunction. NADPH oxidase and serum xanthine
      oxidase activities were significantly reduced by PETN but not by ISMN. Both
      organic nitrates had minor effects on the expression of NADPH oxidase subunits,
      eNOS and dihydrofolate reductase (Western blotting). PETN, but not ISMN,
      normalized the expression of GTP cyclohydrolase-1, extracellular superoxide
      dismutase, and S-glutathionylation of eNOS, thereby preventing eNOS uncoupling.
      The expression of the antioxidant enzyme, HO-1, was increased by STZ treatment
      and further upregulated by PETN, but not ISMN, via activation of the
      transcription factor NRF2. CONCLUSIONS: In contrast to ISMN, the organic nitrate,
      PETN, improves endothelial dysfunction in diabetes by preventing eNOS uncoupling
      and NADPH oxidase activation, thereby reducing oxidative stress. Thus, PETN
      therapy may be suited to treat patients with cardiovascular complications of
      diabetes.

PMID- 21844098
TI  - Reduced serum vitamin D-binding protein levels are associated with type 1
      diabetes.
AB  - OBJECTIVE: Previous studies have noted a specific association between type 1
      diabetes and insufficient levels of vitamin D, as well as polymorphisms within
      genes related to vitamin D pathways. Here, we examined whether serum levels or
      genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic
      actions of vitamin D, specifically associate with the disorder. RESEARCH DESIGN
      AND METHODS: A retrospective, cross-sectional analysis of VDBP levels used
      samples from 472 individuals of similar age and sex distribution, including 153
      control subjects, 203 patients with type 1 diabetes, and 116 first-degree
      relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP)
      typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this
      cohort to determine potential genetic correlations. In addition, SNP analysis of
      a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and
      1,880 control subjects also was used to determine genotype frequencies. RESULTS:
      Serum VDBP levels were highest in healthy control subjects (median 423.5 ug/mL
      [range 193.5-4,345.0; interquartile range 354.1-]586), intermediate in first
      degree relatives (402.9 ug/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1
      diabetic patients (385.3 ug/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control
      subjects). VDBP levels did not associate with serum vitamin D levels, age, or
      disease duration. However, VDBP levels were, overall, lower in male subjects
      (374.7 ug/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 ug/mL
      [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in
      genotype frequencies of the VDBP polymorphisms were associated with serum VDBP
      levels or between type 1 diabetic patients and control subjects. CONCLUSIONS:
      Serum VDBP levels are decreased in those with type 1 diabetes. These studies
      suggest that multiple components in the metabolic pathway of vitamin D may be
      altered in type 1 diabetes and, collectively, have the potential to influence
      disease pathogenesis.

PMID- 21844099
TI  - Hospitals turning to team-based conflict resolution.

PMID- 21844100
TI  - Penalizing hospitals for bad care.

PMID- 21844101
TI  - Calciphylaxis: a severe complication of renal disease.

PMID- 21844102
TI  - A patient with tremor, part 2: from diagnosis to treatment.

PMID- 21844103
TI  - Not all cardiac arrests are the same.

PMID- 21844104
TI  - Better management of chronic pain care for all.

PMID- 21844105
TI  - The skinny on BMI report cards.

PMID- 21844106
TI  - Getting the numbers right in Africa--a tribal solution.

PMID- 21844107
TI  - Hand sanitizers may increase norovirus risk.

PMID- 21844108
TI  - Predictors of survival after cardiac or respiratory arrest in critical care
      units.
AB  - BACKGROUND: Survival outcomes after cardiac or respiratory arrest occurring
      outside of intensive care units (ICUs) has been well described. We investigated
      survival outcomes of adults whose arrest occurred in ICUs and determined
      predictors of decreased survival. METHODS: We reviewed all records of adults who
      experienced cardiac or respiratory arrest from Jan. 1, 2000, to Apr. 30, 2005, in
      ICUs at four hospitals serving Edmonton, Alberta. We evaluated patient and
      clinical characteristics, as well as survival outcomes during a five-year follow
      up period. We determined risk factors for immediate (within 24 hours) and later
      death. RESULTS: Of the 517 patients included in the study, 59.6% were able to be
      resuscitated, 30.4% survived to discharge from ICU, 26.9% survived to discharge
      from hospital, 24.3% survived to one year, and 15.9% survived to five years.
      Pulseless electrical activity or asystole was the most common rhythm (45.8% of
      the arrests). Survival was lowest among patients with an arrest due to pulseless
      electrical activity or asystole: only 10.6% survived to one year, compared with
      36.3% who had other arrest rhythms (p < 0.001). Independent predictors of
      decreased later survival (eight months or more after arrest) were increasing age
      (adjusted hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.09) and
      longer duration of cardiopulmonary resuscitation (CPR) (adjusted HR 1.38, 95% CI
      1.03-1.83, per additional logarithm of a minute of CPR). INTERPRETATION: Our
      study showed no major improvement in survival following cardiac arrest with
      pulseless electrical activity or asystole as the presenting rhythm in the ICU
      despite many advances in critical care over the previous two decades. The
      independent predictors of death within 24 hours after arrest in an ICU were sex,
      the presenting rhythm and the duration of CPR. Predictors of later death (eight
      months or more after arrest) were age and duration of CPR.

PMID- 21844110
TI  - Lament for the humanities in continuing medical education.

PMID- 21844111
TI  - Using the Edmonton obesity staging system to predict mortality in a population
      representative cohort of people with overweight and obesity.
AB  - BACKGROUND: Anthropometric-based classification schemes for excess adiposity do
      not include direct assessment of obesity-related comorbidity and functional
      status and thus have limited clinical utility. We examined the ability of the
      Edmonton obesity staging system, a 5-point ordinal classification system that
      considers comorbidity and functional status, in predicting mortality in a
      nationally representative US sample. METHODS: We analyzed data from the National
      Health and Human Nutrition Examination Surveys (NHANES) III (1988-1994) and the
      NHANES 1999-2004, with mortality follow-up through to the end of 2006. Adults
      (age >= 20 yr) with overweight or obesity who had been randomized to the morning
      session at the mobile examination centre were scored according to the Edmonton
      obesity staging system. We examined the relationship between staging system
      scores and mortality, and Cox proportional hazards models were adjusted for the
      presence of the metabolic syndrome or hypertriglyceridemic waist. RESULTS: Over
      75% of the cohort with overweight or obesity were given scores of 1 or 2. Scores
      of 4 could not be reliably assigned because specific data elements were lacking.
      Survival curves clearly diverged when stratified by scores of 0-3, but not when
      stratified by obesity class alone. Within the data from the NHANES 1988-1994,
      scores of 2 (hazard ratio [HR] 1.57; 95% confidence interval [CI] 1.16 to 2.13)
      and 3 (HR 2.69; 95% CI 1.98 to 3.67) were associated with increased mortality
      compared with scores of 0 or 1, even after adjustment for body mass index and the
      metabolic syndrome. We found similar results after adjusting for
      hypertriglyceridemic waist (i.e., waist circumference >= 90 cm and a triglyceride
      level >= 2 mmol/L for men; the corresponding values for women were >= 85 cm and
      >= 1.5 mmol/L), as well as in a cohort eligible for bariatric surgery.
      INTERPRETATION: The Edmonton obesity staging system independently predicted
      increased mortality even after adjustment for contemporary methods of classifying
      adiposity. The Edmonton obesity staging system may offer improved clinical
      utility in assessing obesity-related risk and prioritizing treatment.

PMID- 21844112
TI  - Comparison between transcranial Doppler and Coulter counter for detection of
      lipid micro embolization from mediastinal shed blood reinfusion during cardiac
      surgery.
AB  - INTRODUCTION: Lipid micro embolization (LME) from re-transfused shed blood has
      been postulated to be a potential reason for short- and long-term cognitive
      dysfunction after cardiac surgery. The purpose of this investigation was to
      evaluate if transcranial Doppler (TCD) has the capacity to detect LME. METHODS:
      Thirteen patients undergoing cardiopulmonary bypass surgery were investigated.
      Each patient's cerebral circulation was monitored with transcranial Doppler
      during the first two minutes after re-transfusion of shed blood and blood was
      simultaneously sampled and characterised by a Coulter counter. RESULTS: Strong
      correlation was found between embolic loads, as measured by transcranial Doppler
      and Coulter counter (r=0.79, P<0.005). CONCLUSIONS: This pilot study shows that
      non-invasive monitoring by transcranial Doppler could be a potential tool to
      monitor LME during cardiopulmonary bypass surgery.

PMID- 21844113
TI  - Near-infrared spectroscopy as a possible device for continuous monitoring of
      arterial carbon dioxide tension during cardiac surgery.
AB  - BACKGROUND: Insufflation of carbon dioxide (CO(2)) to the operative field has
      been used to prevent major organ injury attributed to air embolisms in cardiac
      surgery. However, it may be preferable to avoid hypercapnia induced by CO(2)
      insufflation, owing to its potentially harmful effect. To investigate the
      effectiveness of near-infrared spectroscopy (NIRS) as a possible method for
      continuous monitoring of arterial CO(2) tension during cardiac surgery, we
      evaluated the correlation between the change in arterial CO(2) tension and the
      change in regional cerebral oxygen saturation (rScO(2)) obtained from NIRS in as
      controlled a condition as possible. METHODS: Thirty patients who underwent
      surgical correction for atrial or ventricular septal defects were enrolled in
      this study. Patients who had pulmonary hypertension or other intracardiac
      anomalies were excluded. Anesthetic and cardiopulmonary bypass (CPB) management
      were conducted according to our standard institutional practice. Data obtained
      from arterial blood gas analyses and corresponding regional cerebral oxygen
      saturation (rScO(2)) recorded from NIRS before and after the insufflations of
      CO(2) during CPB were used for analysis. RESULTS: The change in arterial CO(2)
      tension correlated with the change in rScO(2) in the left hemisphere (r = 0.681,
      p <0.001, y = -1.393 + 0.547x) and right hemisphere (r = 0.690, p <0.001, y = 
      1.999 + 0.486x). To control the effects of other variables, including hematocrit
      and temperature, these relationship were not reduced (left hemisphere: r=0.678,
      p<0.001; right hemisphere: r=0.634, p<0.001). CONCLUSIONS: Since the change in
      regional cerebral oxygen saturation was correlated with the change in arterial
      CO(2) tension during mild hypothermic CPB, NIRS might be a possible non-invasive
      method for monitoring of arterial CO(2) tension without incurring additional cost
      in this setting.

PMID- 21844114
TI  - Subset size, activation threshold and distribution of autoreactive MZ and FO B
      cells do not differ in a sex-specific manner in the NZB/W F1 murine lupus model:
      an experimental mouse study.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) shows a strong sex bias,
      preferentially affecting females, and B cells are thought to play a pivotal role
      in its pathogenesis. Here, we compared the splenic B-cell compartments, their
      autoreactivity and activation threshold of female and male NZB/W F1, a murine
      lupus model reflecting the sex bias observed in patients with SLE. METHODS:
      Autoantibody levels and the amount of autoantibody secreting cells were
      determined using ELISA and ELISPOT. Flow cytometry and immunofluorescence were
      applied to analyse the composition of the splenic B-cell pool. Purified
      follicular (FO) and marginal zone (MZ) B cells were stimulated and the frequency
      of autoreactive cells was determined. Finally, the proliferative response of FO
      and MZ B cells upon stimulation was assessed using CFSE dilution and [(3)H]
      Thymidin incorporation. RESULTS: Higher autoantibody titres were detected in
      female NZB/W F1 mice, which were mainly produced in the spleen. Analysing the
      composition of the splenic B-cell subsets, no differences were found prior to
      disease development. Autoreactive dsDNA-specific B cells were mostly found in the
      MZ compartment, while SmD1((83-119))-reactive cells were more evenly distributed.
      Equal frequencies of autoreactive B cells were found in female and malemice, and
      no difference in the response to polyclonal stimuli of the cells of both sexes
      was detected. CONCLUSIONS: No differences in the composition or functionality of
      splenic B cells were observed that account for the different disease course in
      both sexes.

PMID- 21844115
TI  - Implications of immunosuppressive agents in cardiovascular risks and carotid
      intima media thickness among lupus nephritis patients.
AB  - INTRODUCTION: Patients with systemic lupus erythematosus, particularly with lupus
      nephritis (LN), are at risk of premature cardiovascular (CV) disease. OBJECTIVE:
      To determine the association between immunosuppressive medications, traditional
      CV risk factors and carotid intima media thickness (CIMT) among patients with LN.
      METHODOLOGY: This was a cross-sectional study in which consecutive LN patients
      attending the Nephrology/SLE Clinic were evaluated for traditional CV risk
      factors. Detailed information on their treatment was obtained from their medical
      records. CIMT, an excellent marker of subclinical atherosclerosis, was measured
      by B Mode carotid ultrasound. RESULTS: A total of 82 patients with LN with a mean
      age of 33.9 +/- 9.8( )years were recruited. More than half had hypertension (n =
      55, 67.1%) and dyslipidemia (n = 43, 52.4%) as traditional CV risks. Longer
      history and higher cumulative dose of corticosteroids were associated with
      hypertension, but use of intravenous methylprednisolone was associated with lower
      systolic and diastolic blood pressure and lower serum total cholesterol and
      triglyceride levels (p < 0.05 each). Hydroxychloroquine use was associated with
      lower total serum cholesterol and serum low-density lipoprotein levels (p <
      0.05). Although the use of cyclosporine A (CyA) was associated with hypertension
      (p < 0.05), those who received a lower cumulative dose of CyA had thicker CIMT (r
      (s) = -0.33, p =0.01) and CyA use remained an independent predictor of CIMT
      during linear regression analysis. There were no associations between CIMT and
      cumulative dose and duration of steroids, hydroxychloroquine, azathioprine,
      mycophenolic acid and cyclophosphamide. CONCLUSION: Aggressive treatment of
      severe LN and the use of CyA as a steroid-sparing agent may have protective
      effects against premature atherosclerosis.

PMID- 21844116
TI  - Superior vena cava syndrome - changing etiology in the third millennium.
AB  - Superior vena cava syndrome (SVCS), is diagnosed following different degrees of
      central venous system obstruction, which traditionally was caused by infections,
      tumors or fibrosing mediastinitis. Recently the role of SVC thrombosis secondary
      to indwelling central venous devices or pacemaker leads as well as different
      hypercoagulable states have drawn much attention. In the current review we
      present a 58-year-old female patient who underwent recurrent pacemaker
      replacements due to recurrent infections. The patient was hospitalized with
      superior vena cava syndrome and multiple thrombi in the upper body circulation.
      Additionally the evaluation was conducted for thrombophilia, which revealed the
      presence of high titers of antiphospholipid antibodies, suggesting the concurrent
      diagnosis of the antiphospholipid syndrome (APS). This case reflects the changes
      in the etiology of SVCS, and the need for a comprehensive evaluation of patients,
      in the search for additional factors that may complicate a pacemaker insertion,
      such as the presence of antiphospholipid antibodies. We review the relevant
      literature and highlight the importance for an interdisciplinary approach in the
      treatment of SVCS nowadays.

PMID- 21844117
TI  - Enhanced CCR5+/CCR3+ T helper cell ratio in patients with active cutaneous lupus
      erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is characterized by enhanced interferon alpha
      (IFNalpha) levels in serum and in tissue. Since IFNalpha promotes a Th1-biased
      immune response, we hypothesized that a Th1-associated chemokine receptor profile
      should be a typical finding in patients with active CLE. Therefore, peripheral
      blood mononuclear cells were isolated from patients with different CLE subsets (n
      = 15), healthy controls (n = 13) and patients under immunotherapy with IFNalpha
      (n = 7). T helper cells were analysed by flow cytometry for the expression of the
      chemokines receptor CCR5, indicative for Th1 cells, and of CCR3, indicating Th2.
      In addition, intracellular levels of the type I IFN-inducible MxA protein were
      measured. Patients with widespread active CLE skin lesions had a significantly
      increased expression of CCR5, whereas expression of CCR3 was decreased when
      compared with healthy controls. MxA expression was significantly enhanced in all
      investigated CLE subtypes, with the highest levels in patients with widespread
      skin lesions. The enhanced CCR5/CCR3 ratio closely correlated with the MxA levels
      in peripheral lymphocytes and with disease activity. Our analyses revealed that
      active CLE is associated with a systemic type I IFN effect that appears to induce
      a shift towards a Th1-associated chemokine receptor profile. The CCR5/CCR3 T
      helper cell ratio might therefore represent an indirect marker for the disease
      activity in CLE.

PMID- 21844118
TI  - Comparison of increased venous contrast in ischemic stroke using phase-sensitive
      MR imaging with perfusion changes on flow-sensitive alternating inversion
      recovery at 3 Tesla.
AB  - BACKGROUND: Increased venous contrast in ischemic stroke using susceptibility
      weighted imaging has been widely reported, although few reports have compared
      increased venous contrast areas with perfusion change areas. PURPOSE: To compare
      venous contrast on phase-sensitive MR images (PSI) with perfusion change on flow
      sensitive alternating inversion recovery (FAIR) images, and to discuss the
      clinical use of PSI in ischemic stroke. MATERIAL AND METHODS: Thirty patients
      with clinically suspected acute infarction of the middle cerebral artery (MCA)
      territory within 7 days of onset were evaluated. Phase-sensitive imaging (PSI),
      flow-sensitive alternating inversion recovery (FAIR), diffusion-weighted imaging
      (DWI) and magnetic resonance angiography (MRA) were obtained using 3 Tesla
      scanner. Two neuroradiologists independently reviewed the MR images, as well as
      the PSI, DWI, and FAIR images. They were blinded to the clinical data and to each
      other's findings. The abnormal area of each image was ultimately identified after
      both neuroradiologists reached consensus. We analyzed areas of increased venous
      contrast on PSI, perfusion changes on FAIR images and signal changes on DWI for
      each case. RESULTS: Venous contrast increased on PSI and hypoperfusion was
      evident on FAIR images from 22 of the 30 patients (73%). The distribution of the
      increased venous contrast was the same as that of the hypoperfused areas on FAIR
      images in 16 of these 22. The extent of these lesions was larger than that of
      lesions visualized by on DWI in 18 of the 22 patients. Hypointense signals
      reflecting hemorrhage and no increased venous contrast on PSI and hyperperfusion
      on FAIR images were found in six of the remaining eight patients (20%). Findings
      on PSI were normal and hypoperfusion areas were absent on FAIR images of two
      patients (7%). CONCLUSION: Increased venous contrast on PSI might serve as an
      index of misery perfusion and provide useful information.

PMID- 21844119
TI  - MicroRNA regulation in mammalian adipogenesis.
AB  - Adipogenesis, the complex development from preadipocytes or mesenchymal stem
      cells to mature adipocytes, is essential for fat formation and metabolism of
      adipose tissues in mammals. It has been reported to be regulated by hormones and
      various adipogenic transcription factors which are expressed as a transcriptional
      cascade promoting adipocyte differentiation, leading to the mature adipocyte
      phenotype. Recent findings indicate that microRNAs (miRNAs), a family of small
      RNA molecules of approximately 22 nucleotides in length, are involved in the
      regulatory network of many biological processes, including cell differentiation,
      through post-transcriptional regulation of transcription factors and/or other
      genes. In this review, we focus on the recent understanding of the roles of
      miRNAs in adipogenesis, including the most recent and relevant findings that
      support the role of several miRNAs as pro- or antiadipogenic factors regulating
      adipogenesis in mice, human and cattle to propose the future role of miRNA in
      adipogenesis of farm animal models.

PMID- 21844120
TI  - Solidago chilensis Meyen hydroalcoholic extract reduces JNK/IkappaB pathway
      activation and ameliorates insulin resistance in diet-induced obesity mice.
AB  - Hydroalcoholic extract of Solidago chilensis (Sc) is employed in popular medicine
      to treat inflammatory disease. The low-grade proinflammatory state and the
      activation of serine/threonine kinases in adipose tissue, like c-jun kinase (JNK)
      and IKK, and transcription factors, have an important role in obesity-associated
      insulin resistance. The aim of this study was to further investigate the effects
      of the Sc extract on glucose homeostasis in diet-induced obesity mice. Male Swiss
      mice were randomized to three groups: a control group (C) fed with standard
      laboratory chow; a group with an experimental high-fat diet (HFD); and a group
      fed with a high-fat (45% kcal from fat) diet + extract of Sc (via
      intraperitoneal, 3 mg/kg) (ScHFD). The dietary treatment lasted for eight weeks.
      Subsequently, the expression and phosphorylation of proteins of interest in the
      liver, hypothalamus and skeletal muscle were evaluated by Western blot analysis.
      Body weight, epididymal fat pad mass and liver triglycerides were higher in HFD
      than in control mice, but these parameters were reduced by intraperitoneal
      administration of the extracts (3 mg/kg) to the HFD group. AKT phosphorylation
      stimulated by insulin in the liver, hypothalamus and skeletal muscle was higher
      in ScHFD as compared with HFD mice. Additionally, liver expression of
      phosphoenolpyruvate carboxykinase (PEPCK) and fatty acid synthase were lower in
      ScHFD as compared with HFD mice. Nuclear factor kappaB, p-IkappaB and p-JNK
      levels were higher in HFD when compared with control mice, but they were lowered
      by treatment with extract (ScHFD). In addition, in db/db mice, Sc extract also
      improved liver AKT phosphorylation stimulated by insulin and reduced PEPCK
      expression. The data presented herein show that Sc improves AKT activation. This
      effect may be promoted by reduction of the proinflammatory pathway in the liver
      and hypothalamus. Therefore, systemic action of the Sc components may contribute
      to improve obesity-associated pathophysiology.

PMID- 21844121
TI  - BLCAP induces apoptosis in human Ewing's sarcoma cells.
AB  - Bladder cancer-associated protein (BLCAP) is a novel candidate tumor suppressor
      gene identified from human bladder carcinoma and highly associated with the
      invasion of bladder cancer. We previously reported that it also plays a key role
      in the tumorigenesis and metastasis of human osteosarcoma. In the present study,
      we constructed a recombinant encoding BLCAP cDNA. Overexpression of BLCAP
      resulted in growth inhibition and induced apoptosis of human TC-135 Ewing's
      sarcoma cells in vitro. We further investigated the caspase-3/7 activity and
      expressions of the fusion transcription factor Ewing's sarcoma protein-friend
      leukemia virus integration 1 (EWS-FLI1) and the apoptosis regulator B-cell
      lymphoma 2 (BCL-2). Cell apoptosis was accompanied by the down-regulated
      expression of EWS-FLI1 and BCL-2. Our present results suggest that BLCAP may play
      a role not only in regulating cell proliferation but also in coordinating
      apoptosis through the down-regulation of BCL-2 and EWS-FLI1 in human Ewing's
      sarcoma cells.

PMID- 21844122
TI  - Subclinical vitamin A deficiency does not increase development of tumors in
      irradiated or unirradiated lungs.
AB  - Cancer patients often have subclinical vitamin A deficiencies and low vitamin A
      lung levels. Previous studies showed that subclinical vitamin A deficiency
      increased the severity of pneumonitis induced by whole-lung irradiation in rats.
      Many studies have shown that lung irradiation increases the number of lung tumors
      developing from intravenously injected tumor cells in mice. We examined the
      impact of vitamin A deficiency on the development of lung metastases from a
      highly metastatic syngeneic rat rhabdomyosarcoma in normal rats and rats
      receiving prior lung irradiation. Weanling female WAGrijY rats were randomized to
      receive either a diet lacking both vitamin A and beta-carotene or a control diet.
      After five weeks, the deficient diet significantly decreased levels of retinol in
      the lung and liver but not in the serum, modeling the tissue and blood levels
      seen in prior studies of patients with subclinical vitamin A inadequacy. The
      vitamin A-deficient diet did not alter the number of lung tumors developing from
      intravenously injected tumor cells in unirradiated rats. Whole-lung irradiation
      produced dose-dependent increases in the number of lung tumors developing from
      tumor cells injected intravenously one or 29 d after irradiation. Vitamin A
      deficiency did not alter these dose-response curves, indicating that the more
      intense radiation-induced pneumonitis seen previously in vitamin A-deficient rats
      did not alter the enhancement of metastases produced by whole-lung irradiation.
      Moreover, inadequate vitamin A intake did not influence the growth of tumors
      implanted subcutaneously or increase the number or size of the spontaneous lung
      metastases developing from these subcutaneous tumors. Thus, although low vitamin
      A status influences the development of lung injury and is considered a possible
      modifiable risk factor increasing risk of primary cancer, it did not affect the
      growth of subcutaneous tumors or increase the development of artificial or
      spontaneous lung metastases in this rat model.

PMID- 21844123
TI  - Digital gene expression for non-model organisms.
AB  - Next-generation sequencing technologies offer new approaches for global
      measurements of gene expression but are mostly limited to organisms for which a
      high-quality assembled reference genome sequence is available. We present a
      method for gene expression profiling called EDGE, or EcoP15I-tagged Digital Gene
      Expression, based on ultra-high-throughput sequencing of 27-bp cDNA fragments
      that uniquely tag the corresponding gene, thereby allowing direct quantification
      of transcript abundance. We show that EDGE is capable of assaying for expression
      in >99% of genes in the genome and achieves saturation after 6-8 million reads.
      EDGE exhibits very little technical noise, reveals a large (10(6)) dynamic range
      of gene expression, and is particularly suited for quantification of transcript
      abundance in non-model organisms where a high-quality annotated genome is not
      available. In a direct comparison with RNA-seq, both methods provide similar
      assessments of relative transcript abundance, but EDGE does better at detecting
      gene expression differences for poorly expressed genes and does not exhibit
      transcript length bias. Applying EDGE to laboratory mice, we show that a loss-of
      function mutation in the melanocortin 1 receptor (Mc1r), recognized as a
      Mendelian determinant of yellow hair color in many different mammals, also causes
      reduced expression of genes involved in the interferon response. To illustrate
      the application of EDGE to a non-model organism, we examine skin biopsy samples
      from a cheetah (Acinonyx jubatus) and identify genes likely to control
      differences in the color of spotted versus non-spotted regions.

PMID- 21844124
TI  - Noncoding RNA gene silencing through genomic integration of RNA destabilizing
      elements using zinc finger nucleases.
AB  - Zinc finger nucleases (ZFNs) allow site-specific manipulation of the genome. So
      far, the use of ZFNs to create gene knockouts has been restricted to protein
      coding genes. However, non-protein-encoding RNAs (ncRNA) play important roles in
      the cell, although the functions of most ncRNAs are unknown. Here, we describe a
      ZFN-based method suited for the silencing of protein-coding and noncoding genes.
      This method relies on the ZFN-mediated integration of RNA destabilizing elements
      into the human genome, e.g., poly(A) signals functioning as termination elements
      and destabilizing downstream sequences. The biallelic integration of poly(A)
      signals into the gene locus of the long ncRNA MALAT1 resulted in a 1000-fold
      decrease of RNA expression. Thus, this approach is more specific and 300 times
      more efficient than RNA interference techniques. The opportunity to create a
      variety of loss-of-function tumor model cell lines in different cancer
      backgrounds will promote future functional analyses of important long noncoding
      RNA transcripts.

PMID- 21844125
TI  - Genetic variation in radiation-induced cell death.
AB  - Radiation exposure through environmental, medical, and occupational settings is
      increasingly common. While radiation has harmful effects, it has utility in many
      applications such as radiotherapy for cancer. To increase the efficacy of
      radiation treatment and minimize its risks, a better understanding of the
      individual differences in radiosensitivity and the molecular basis of radiation
      response is needed. Here, we integrated human genetic and functional genomic
      approaches to study the response of human cells to radiation. We measured
      radiation-induced changes in gene expression and cell death in B cells from
      normal individuals. We found extensive individual variation in gene expression
      and cellular responses. To understand the genetic basis of this variation, we
      mapped the DNA sequence variants that influence expression response to radiation.
      We also identified radiation-responsive genes that regulate cell death; silencing
      of these genes by small interfering RNA led to an increase in radiation-induced
      cell death in human B cells, colorectal and prostate cancer cells. Together these
      results uncovered DNA variants that contribute to radiosensitivity and identified
      genes that can be targeted to increase the sensitivity of tumors to radiation.

PMID- 21844126
TI  - The use of high-fidelity simulation to teach home care nursing.
AB  - The use of high-fidelity human patient simulation (HPS) is increasing in nursing
      education, yet little is known about its use in community health. This study
      examined an HPS home care experience to determine effects on three outcomes
      (student satisfaction, self-confidence, and learning). In addition, design
      characteristics of the simulation and demographic characteristics of students
      were examined for correlation with these outcomes. Senior baccalaureate students
      took part in the experience. Results indicated that students were very satisfied
      with the experience and felt it increased their confidence in providing care in
      the home, although learning outcomes were not high. Although no demographic
      characteristics were found to be correlated with outcomes, five design
      characteristics of a simulation were moderately correlated with the outcomes of
      satisfaction and self-confidence, especially support. It is recommended that
      nurse educators design HPS home care simulation experiences that provide student
      support prior to their first home care visit.

PMID- 21844127
TI  - Effects of human endothelial gene polymorphisms on cellular responses to
      hyperglycaemia: role of NOS3 (Glu298Asp) and ACE (I/D) polymorphisms.
AB  - The functional relevance of NOS3 and ACE genetic variations to endothelial cell
      function is largely unstudied. Here we tested the functional relevance of the
      NOS3 (Glu298Asp) polymorphism and ACE (I/D) polymorphism in endothelial cells in
      vitro. Our hypothesis was that these genetic polymorphisms alter endothelial cell
      sensitivity to glucose and 3-nitrotyrosine (3NT). Genotyped HUVECs were incubated
      with glucose, free 3NT or a combination of these two toxicants. Significant
      differences in glucose-induced cell death and free 3NT-induced cell death were
      observed among the NOS3 genotypes. Combined glucose/3NT caused increased toxicity
      among the NOS3 genotypes. No differences were observed among the ACE genotypes in
      their responses to glucose/3NT. These data demonstrate that the NOS3 genotype may
      be an important predictor of, or be mechanistically involved in, endothelial
      vulnerability, whereas the ACE I/D genotype is apparently less important. Thus
      this NOS3 genetic variation may play a role in vulnerability to endothelium
      dependent diabetic vascular complications.

PMID- 21844128
TI  - Fibrin(ogen) may be an important target for methylglyoxal-derived AGE
      modification in elastic arteries of humans.
AB  - Diabetes is associated with increased risk of cardiovascular disease. Advanced
      glycation end-products (AGEs) are considered to be a major pathogenic factor for
      diabetic vascular complications. The levels of AGEs are increased in diabetic
      patients. We have studied the presence of the major AGE methylglyoxal (MGO)
      derived hydroimidazolone in human aorta and carotid arteries, using
      immunohistochemistry (IHC), western blotting and mass spectrometry. By IHC, MGO
      derived modifications were detected mainly associated with cells in intimal
      thickenings and cells in microvessels in adventitia. In type V lesions MGO
      derived AGE was also present, extracellular in the necrotic core and in cells at
      the border of the core. The highest degree of modification was probably
      associated with cell nuclei. By western blotting and mass spectrometry
      fibrin(ogen), the cytoskeleton-associated protein moesin and the nuclear proteins
      lamin A and C were identified as putative main targets for MGO-derived
      modification. LC-MS/MS studies of fibrin(ogen) modified in vitro with low
      concentrations of MGO identified the sites that were most prone to modification.
      These results indicate that AGE modifications occur preferentially on specific
      proteins. The modification of these proteins may play a role in vascular
      dysfunction and development of atherosclerosis in diabetes.

PMID- 21844129
TI  - Development of an electrochemical Limulus amebocyte lysate assay technique for
      portable and highly sensitive endotoxin sensor.
AB  - Here, we report the development of an electrochemical detection method for
      endotoxin based on the Limulus amebocyte lysate (LAL) assay. A mixture of LAL
      reagent and endotoxin sample solution was incubated for 1 h. The endotoxin
      activated a cascade reaction of zymogens contained in the LAL to generate p
      nitroaniline (pNA) which was then electrochemically detected by differential
      pulse voltammetry (DPV). The generated pNA gave a clear peak at -0.75 V vs.
      silver/silver chloride (Ag/AgCl), which increased with the concentration of
      endotoxin in the LAL assay solution. This DPV detection was performed using an
      electrode chip device fabricated from a diamond-like carbon-coated glass
      substrate. This chip device could detect as low as 10 endotoxin units l(-1) at
      room temperature within 1 h. This novel electrochemical method for the detection
      of endotoxin appears promising for the development of compact, low-cost and easy
      to-use sensors for on-site monitoring of potentially contaminated medical
      supplies, including dialysis fluid, transplanted tissue and culture medium for
      assisted reproduction.

PMID- 21844130
TI  - Immunization with an anti-idiotypic antibody against the broadly
      lipopolysaccharide-reactive antibody WN1 222-5 induces Escherichia coli R3-core
      type specific antibodies in rabbits.
AB  - The mouse monoclonal antibody (mAb) WN1 222-5 recognizes a carbohydrate epitope
      in the inner core region of LPS that is shared by all strains of Escherichia coli
      and Salmonella enterica and is able to neutralize their endotoxic activity in
      vitro and in vivo. Immunization of mice with mAb WN1 222-5 yielded several anti
      idiotypic mAbs one of which (mAb S81-19) competitively inhibited binding of mAb
      WN1 222-5 to E. coli and Salmonella LPS. After immunization of rabbits with mAb
      S81-19, the serological responses towards LPS were characterized at intervals
      over two years. Whereas the serological response against the anti-idiotype
      developed as expected, the anti-anti-idiotypic response against LPS developed
      slowly and antibodies appeared after 200 d that bound to E. coli LPS of the R3
      core-type and neutralized its TNF-alpha inducing capacity for human peripheral
      mononuclear cells. We describe the generation of a novel anti-idiotypic antibody
      that can induce LPS core-reactive antibodies upon immunization in rabbits and
      show that it is possible, in principle, to obtain LPS neutralizing antibodies by
      anti-idiotypic immunization against the mAb WN1 222-5. The mimicked epitope
      likely shares common determinants with the WN1 222-5 epitope, yet differences
      with respect to either affinity or specificity do exist, as binding to smaller
      oligosaccharides of the inner core was not observed.

PMID- 21844131
TI  - Targeted therapy for NSCLC: ALK inhibition.
AB  - PURPOSE: The purpose of this review article is to describe the emerging data of
      ALK receptor tyrosine kinaase inhibitors in ALK mutation positive NSCLC. SUMMARY:
      ALK mutations have been identified in approximately 2.4-13% of patients with
      NSCLC, occurring more frequently in adenocarcinomas and never and light smokers.
      Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET
      tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at
      nanomolar concentrations. A phase II study demonstrated an overall response rate
      of 57% (95% CI, 46 to 68), with the most common toxicity grade I fatigue and
      visual disturbances. Elevations in lever function tests were also reported.
      CONCLUSION: The ALK receptor tyrosine kinase inhibitor crizotinib may be an
      effective therapy in ALK mutated NSCLC and is currently being compared to
      standard chemotherapy for advanced or metastatic NSCLC.

PMID- 21844132
TI  - Effect of imatinib therapy with and without turmeric powder on nitric oxide
      levels in chronic myeloid leukemia.
AB  - Nitric oxide (NO) is involved in different stages of malignancies. Increased
      levels of NO have been reported in different leukemias. Imatinib is the preferred
      drug for the treatment of chronic myeloid leukemia (CML). Turmeric powder
      contains curcumin which has anti-leukemic property and also decreases NO
      synthesis. This study was conducted on fifty patients of CML divided into two
      groups, group A receiving imatinib alone and group B receiving turmeric powder
      along with imatinib for six weeks. Nitric oxide levels were estimated in these
      patients before and after receiving therapy and were analyzed statistically.
      Nitric oxide levels were found to be significantly decreased in both the groups,
      but more significantly in group B after receiving the respective treatments.
      Thus, curcumin acts as an adjuvant to imatinib in decreasing the NO levels and
      may help in the treatment of CML patients.

PMID- 21844134
TI  - Endoluminal versus open repair of descending thoracic aortic rupture: a review of
      the National Trauma Databank.
AB  - OBJECTIVES: Open repair for blunt thoracic aortic injury is associated with
      significant mortality. Interest in less invasive methods of repair has developed
      and results of several clinical studies have shown successful emergency repair
      with endovascular stent grafting. The purpose of this report was to compare
      endoluminal versus open repair of traumatic thoracic aortic injury in the
      National Trauma Databank. METHODS: We queried the databank from 2002 to 2006. We
      selected patients who had one of their International Classification of Disease-9
      Diagnoses as 901.0, 'injury to the thoracic aorta', whose mechanism of injury was
      motor vehicle accident, fall or other transport, whose discharge disposition was
      known, and who received an endovascular or open repair. RESULTS: The search
      resulted in 997 patients, one of whom had both procedures listed and was excluded
      from the analysis, 72% were males. A total of 875 underwent open repair and 121
      had endoluminal repair. Both groups were similar in terms of age, demographics,
      associated injuries and hemodynamic status on presentation. Neither method of
      repair conferred significant advantage of survival, length of stay or ventilator
      days. Furthermore, there was no significant difference of pulmonary, renal,
      cardiac, infectious and neurologic complications between the two methods.
      CONCLUSION: Our findings suggest that in a large unselected population,
      endoluminal repair for aortic thoracic injury is not associated with decreased
      mortality or overall morbidity. Long-term data for endoluminal repair and its
      durability are lacking, especially in young patients. It may be premature to
      adopt endoluminal repair as the method of choice for all of these patients.

PMID- 21844135
TI  - Residential segregation, health behavior and overweight/obesity among a national
      sample of African American adults.
AB  - We examined the role of residential segregation in 5+ daily fruit/vegetable
      consumption, exercise, and overweight/obesity among African Americans by linking
      data on the 11,142 African American adults in the 2000 Behavioral Risk Factor
      Surveillance System to 2000 census data on the segregation of metropolitan
      statistical areas (MSAs). Multi-level modeling revealed that after controlling
      for individual-level variables, MSA Segregation and Poverty contributed to
      fruit/vegetable consumption, MSA Poverty alone contributed to exercise, and MSA
      Segregation alone contributed to overweight/obesity. These findings highlight the
      need for research on the built-environments of the segregated neighborhoods in
      which most African Americans reside, and suggest that neighborhood disparities
      may contribute to health disparities.

PMID- 21844136
TI  - Do beta-blockers alter dyspnea and fatigue in advanced lung cancer? A
      retrospective analysis.
AB  - INTRODUCTION: Dyspnea is common in lung cancer and may be partially attributable
      to increased ventilatory drive due to muscle weakness. The sympathetic component
      of this pathway might be mitigated by beta-blockers. METHODS: A retrospective
      review of new patients with stage III-IV non-small lung cancer or any small cell
      lung cancer was undertaken to assess the impact of beta-blocker use on dyspnea
      and fatigue. Data were abstracted for clinical characteristics, beta-blocker use,
      and pre-treatment Edmonton Symptom Assessment System dyspnea and fatigue scores.
      RESULTS: Of 348 patients assessed, 202 met eligibility criteria. The median age
      was 67, 55.4% were female, 18.8% had chronic obstructive pulmonary disease
      (COPD), and 5.9% had active coronary artery disease. Over 60% of patients scored
      4/10 or higher on their dyspnea and fatigue scores. While dyspnea and fatigue
      were moderately associated, no association was found between beta-blocker use and
      either symptom. Recorded dosages of beta-blockers were low. COPD was associated
      with dyspnea and fatigue, while anemia was associated with fatigue. CONCLUSIONS:
      Dyspnea and fatigue are prevalent and increased in the presence of COPD and
      anemia. No association between beta-blocker use and dyspnea or fatigue scores was
      observed. This may be attributable to inadequate dosing or to retrospective bias.

PMID- 21844137
TI  - Qualitative research in evidence-based medicine: improving decision-making and
      participation in randomized controlled trials of cancer treatments.
AB  - BACKGROUND: Since the 1990s there has been increasing emphasis on 'evidence-based
      medicine'. The randomized controlled trial is widely regarded as the 'gold
      standard' study design for evaluating interventions. However, placing too strong
      an emphasis on a phase III trial, to the neglect of earlier development and
      piloting work, may result in weaker interventions that are more difficult to
      evaluate and less likely to be implemented. AIM: To illustrate the benefits and
      outcomes of qualitative research at the early stages of the research continuum.
      SETTING/PARTICIPANTS: Two cancer studies are evaluated in which the best
      treatment option is uncertain: ASPECTS (A Study of Patients ExperienCes of
      TreatmentS) and ProtecT (Prostate Testing for Cancer and Treatment). DESIGN: To
      examine decision-making in relation to palliative chemotherapy for advanced
      cancer, ASPECTS was a qualitative study involving non-participant observation and
      recording of oncology consultations. During the ProtecT feasibility study,
      recruitment interviews were routinely audiotaped and in-depth interviews
      conducted with men to explore their understanding of treatment options and
      randomization to trial arms. RESULTS: ASPECTS identified that insufficient
      information was given to patients about the survival benefits of palliative
      chemotherapy with implications for informed consent. ProtecT illustrated the
      effective use of qualitative research methods to resolve recruitment and
      randomization problems for a randomized controlled trial. CONCLUSIONS: These
      studies illustrate the value of qualitative research, particularly during the
      earlier phases of the research continuum. Such research may generate hypotheses,
      strengthen the development and implementation of interventions and enhance their
      evaluation: all of which are essential to evidence-based medicine.

PMID- 21844138
TI  - Designing and conducting randomized controlled trials in palliative care: A
      summary of discussions from the 2010 clinical research forum of the Australian
      Palliative Care Clinical Studies Collaborative.
AB  - Rigorous clinical research in palliative care is challenging but achievable.
      Trial participants are likely to have deteriorating performance status, co
      morbidities and progressive disease. It is difficult to recruit patients, and
      attrition unrelated to the intervention being trialled is high. The aim of this
      paper is to highlight practical considerations from a forum held to discuss these
      issues by active palliative care clinical researchers. To date, the Australian
      Palliative Care Clinical Studies Collaborative (PaCCSC) has randomized more than
      500 participants across 12 sites in 8 Phase III studies. Insights from the 2010
      clinical research forum of the PaCCSC are reported. All active Australian
      researchers in palliative care were invited to present their current research and
      address three specific questions: (1) What has worked well? (2) What didn't work
      well? and (3) How should the research be done differently next time? Fourteen
      studies were presented, including six double-blind, randomized, controlled, multi
      site trials run by the PaCCSC. Key recommendations are reported, including
      guidance on design; methodologies; and strategies for maximizing recruitment and
      retention. These recommendations will help to inform future trial design and
      conduct in palliative care.

PMID- 21844139
TI  - Influence of Janus kinase inhibition on interleukin 6-mediated induction of acute
      phase serum amyloid A in rheumatoid synovium.
AB  - OBJECTIVE: Inhibition of intracellular signal transduction is considered to be a
      therapeutic target for chronic inflammation. The new Janus kinase (JAK)3
      inhibitor CP690,550 has shown efficacy in the treatment of rheumatoid arthritis
      (RA). We investigated the influence of JAK/STAT inhibition using CP690,550 on the
      induction of acute-phase serum amyloid A (SAA), which is triggered by interleukin
      6 (IL-6) stimulation in rheumatoid fibroblast-like synoviocytes (RA-FLS).
      METHODS: IL-6-stimulated gene expression of the acute-phase serum amyloid A genes
      (A-SAA; encoded by SAA1+SAA2) and SAA4 was analyzed by reverse transcriptase
      polymerase chain reaction. The intracellular signaling pathway mediating the
      effects of CP690,550 on IL-6-stimulated JAK/STAT activation was assessed by
      measuring the phosphorylation levels using Western blots. RESULTS: IL-6 trans
      signaling induced A-SAA messenger RNA (mRNA) expression in RA-FLS. By contrast IL
      6 stimulation did not affect SAA4 mRNA expression, which is expressed
      constitutively in RA-FLS. IL-6 stimulation elicited rapid phosphorylation of JAK2
      and STAT3, which was blunted by CP690,550. CP690,550 abrogated IL-6-mediated A
      SAA mRNA expression in RA-FLS. Similarly, CP690,550 inhibited IL-6-mediated A-SAA
      mRNA expression in human hepatocytes. CONCLUSION: Our data indicated that
      CP690,550 blocked IL-6-induced JAK2/STAT3 activation, as well as the induction of
      A-SAA. Inhibition of IL-6-mediated proinflammatory signaling pathways by
      CP690,550 may represent a new antiinflammatory therapeutic strategy for RA and AA
      amyloidosis.

PMID- 21844140
TI  - Effect of pregnancy on ankylosing spondylitis: a case-control study.
AB  - OBJECTIVE: To evaluate the effect of pregnancy on ankylosing spondylitis (AS).
      METHODS: Our study aimed to determine the severity of back pain and stiffness pre
      , during, and postpartum in patients with AS and controls, and corresponding
      extraarticular symptoms. RESULTS: Nineteen female patients with AS (35
      pregnancies) and 33 controls (77 pregnancies) were studied. Improvement in pain
      was reported in 51% of AS patients, predominantly in the first trimester, with
      significant improvement in pain than stiffness. In both groups, pain worsened in
      later stages, likely secondary to biomechanical loading. Postpartum pain scores
      in AS returned to prepartum levels in general. CONCLUSION: Pregnancy does not
      substantially aggravate disease activity or severity in AS.

PMID- 21844141
TI  - Mortality in patients with biopsy-proven giant cell arteritis: a south australian
      population-based study.
AB  - OBJECTIVE: To compare mortality rates and cause of death in patients with biopsy
      proven giant cell arteritis (GCA) with those in the general population. METHODS:
      Patients with biopsy-proven GCA were identified from pathology reports of
      temporal artery biopsies in South Australia, from January 1, 1992, to December
      31, 2006. All patients with biopsy-proven GCA were linked to the South Australian
      Births, Death and Marriage Registry to identify deaths until December 31, 2006.
      Standardized mortality ratios and relative survival (ratio of observed survival
      in GCA group to expected survival of general South Australian population, matched
      by age, sex, and calendar time) were calculated. The cause of death recorded on
      the death certificate was also documented. RESULTS: There were 225 cases of
      biopsy-proven GCA (163 women and 62 men). The mean age at diagnosis of GCA was
      78.2 years. The mean followup period was 66.2 months (SD 47.1 mo). During the
      followup period, there were 71 deaths in the GCA group (50 women, 21 men). The
      standardized mortality ratio was 0.99 (95% CI 0.77-1.25). The relative survival
      for different followup periods demonstrates that patients with GCA experienced
      similar mortality to the general population (age-matched and sex-matched). Death
      from cardiovascular causes (45%) was the most common, followed by infection (17%)
      and cancer (17%). Infection was a significantly more common cause of death in the
      first year (chi-squared, p = 0.0002). CONCLUSION: Our population-based cohort
      study did not demonstrate any increased mortality risk for patients diagnosed
      with biopsy-proven GCA. The risk of death from infection early in the disease may
      be increased.

PMID- 21844142
TI  - Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma
      (PHAROS): baseline characteristics and description of study population.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) increases mortality in systemic
      sclerosis (SSc). The multicenter PHAROS registry (Pulmonary Hypertension
      Assessment and Recognition of Outcomes in Scleroderma) prospectively follows
      subjects with SSc at high risk for or with incident pulmonary hypertension (PH).
      We describe the registry design and baseline characteristics of subjects enrolled
      during the first 18 months since the start of the study. METHODS: High-risk
      subjects are enrolled and classified as Pre-PAH if they have (1) carbon monoxide
      diffusing capacity (DLCO) < 55% predicted; (2) percentage of predicted forced
      vital capacity/DLCO ratio >= 1.6; or (3) an estimated right ventricular systolic
      pressure > 35 mm Hg on echocardiography. Subjects with right heart
      catheterization (RHC)-confirmed incident PH (mean pulmonary artery pressure >= 25
      mm Hg within previous 6 months) are subclassified into PAH, pulmonary venous
      hypertension secondary to left-side heart disease (PVH), and PH due to
      interstitial lung disease (PH-ILD). Baseline and biannual demographic, clinical,
      and laboratory data and patient-reported health questionnaires are collected.
      RESULTS: There are 237 subjects enrolled in PHAROS. The majority are white (73%)
      and women (87%). There are 166 Pre-PAH and 71 Definite PH subjects (49 PAH, 7
      PVH, and 15 PH-ILD). CONCLUSION: PHAROS is the largest US and Canadian cohort of
      subjects with SSc at high risk for or with incident PAH. PAH-specific therapies
      are approved for 49/71 subjects with RHC-confirmed PAH. Analyses of PHAROS
      registry data will permit identification of risk factors for development of PAH
      among SSc patients at high risk for PAH and enhance understanding of the course
      of SSc-PAH.

PMID- 21844143
TI  - Multiple oral Candida infections in patients with Sjogren's syndrome --
      prevalence and clinical and drug susceptibility profiles.
AB  - OBJECTIVE: To determine the prevalence of oral candidiasis and multiple oral
      Candida infections in patients with primary Sjogren's syndrome (SS), and the
      clinical and drug susceptibility profile. METHODS: Thirty patients with primary
      SS were enrolled in our study. The diagnosis of oral candidiasis was based on the
      clinical manifestation, and confirmed by a concentrated rinse culture. Candida
      spp. assessment was accomplished using standard methods: Sabouraud dextrose agar
      with 50 mg/l chloramphenicol and CHROMagar were used for the rapid screening of
      clinical species, followed by the API 20C system for further species
      identification. In vitro antifungal drug susceptibility of Candida isolates was
      determined by the minimal inhibitory concentrations. RESULTS: In our study, 87%
      (26/30) of subjects had oral candidiasis, in which 42% (11/26) had multiple
      Candida spp. infection. Although C. albicans remains the predominant isolate,
      other rare species such as C. tropicalis, C. glabrata, C. parapsilosis, and C.
      krusei were present, alone or in combination. Chronic atrophic candidiasis is the
      most common clinical type of oral candidiasis in patients with SS. The
      susceptibilities of the 44 Candida isolates to 7 antifungal agents varied
      dramatically. The resistance to azoles was remarkable, and the phenomenon of
      cross-resistance between itraconazole and fluconazole was observed. CONCLUSION:
      Patients with primary SS carry a high risk of oral candidiasis and a high
      frequency of multiple Candida infections. The azole resistance patterns of
      Candida spp. support the necessity for drug susceptibility testing as a routine
      procedure for patients with oral Candida infections.

PMID- 21844144
TI  - Predictors of longterm mortality in patients with and without systemic lupus
      erythematosus on maintenance dialysis: a comparative study.
AB  - OBJECTIVE: To compare the prognosis of patients with and without systemic lupus
      erythematosus (SLE) on dialysis and to determine the factors that affect survival
      after dialysis. METHODS: We used the Taiwan National Health Insurance Research
      Database (NHRI-NHIRD-99182) and collected data on patients who started
      maintenance dialysis between 2001 and 2003. Patients were followed from the
      initiation of dialysis until death, discontinuation of dialysis, or the end of
      2008. We did a Kaplan-Meier analysis of the cohort and used multivariate Cox
      regression analysis to identify significant predictors of survival. RESULTS: Of
      the 22,394 dialysis patients studied, 303 (1.35%) had SLE. Hypertension and
      diabetes were the 2 most common comorbidities associated with dialysis for
      patients with and without SLE. After adjusting for age, sex, dialysis modality,
      and comorbidities, we found no significant survival difference between the 2
      patient groups after 8 years of followup. Multivariate analysis showed that
      increased mortality in the patient group without SLE (p < 0.05) was associated
      with older age (>= 45 years), male sex, initial choice of hemodialysis, diabetes
      mellitus, heart failure, coronary artery disease, cerebrovascular disease, and
      malignancy. In the patient group with SLE, independent predictors of mortality (p
      < 0.05) were older age (>= 65 years), male sex, and diabetes mellitus.
      CONCLUSION: The longterm survival outcome was similar between patients with and
      without SLE who were on dialysis. The factors affecting patient mortality were
      not identical in these 2 groups.

PMID- 21844145
TI  - Idiopathic inflammatory myopathy associated with malignancy: a retrospective
      cohort of 151 Korean patients with dermatomyositis and polymyositis.
AB  - OBJECTIVE: To define the standardized incidence ratio (SIR) of malignancy and
      factors associated with malignancies in Korean patients with dermatomyositis (DM)
      and polymyositis (PM). METHODS: The demographic, clinical, and laboratory
      features of 151 patients diagnosed with DM/PM were compared in patients with and
      without malignancies. RESULTS: Malignancies were found in 23 of 98 patients with
      DM (23.5%) and in 2 of 53 with PM (3.8%). Lung cancer (8 patients) was the most
      common malignancy. Compared with the period-specific, sex-matched, and age
      matched Korean population, the SIR for malignancy in patients with DM was 14.2
      (95% CI 9.0-21.3). Univariate analysis showed that factors associated with
      malignancy included older age (p < 0.001), DM (p = 0.002), dysphagia (p < 0.001),
      the absence of interstitial lung disease (ILD; p = 0.001), and lower elevations
      in aspartate aminotransferase (p = 0.005) and lactate dehydrogenase
      concentrations (p < 0.001). Multivariate analysis showed that factors
      independently associated with malignancy included older age (per 10 years, OR
      2.3, 95% CI 1.6-3.5, p < 0.001), DM (OR 5.9, 95% CI 1.3-26.2, p = 0.020),
      dysphagia (OR 2.6, 95% CI 1.2-6.6, p = 0.042), and the absence of ILD (OR 0.1,
      95% CI 0.01-0.9, p = 0.040). CONCLUSION: DM was associated with a greater risk of
      concomitant malignancies, especially lung cancer, than PM. Independent factors
      associated with malignancies in patients with DM/PM were older age, the presence
      of dysphagia, and the absence of ILD.

PMID- 21844146
TI  - Hepatitis B virus reactivation by immunosuppressive therapy in patients with
      autoimmune diseases: risk analysis in Hepatitis B surface antigen-negative cases.
AB  - OBJECTIVE: To evaluate the risk of reactivation of resolved hepatitis B virus
      (HBV) by immunosuppressive therapy in patients with autoimmune diseases. METHODS:
      Thirty-five patients with autoimmune diseases were included in our study; all
      were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis
      B core antigen-positive. They were followed for 8-124 weeks and clinical outcomes
      were analyzed, including serum levels of HBV-DNA and aminotransferase every 4
      weeks during their immunosuppressive therapy for underlying autoimmune diseases.
      If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody
      against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against
      HBeAg were also monitored every 4 weeks. RESULTS: HBV-DNA was detected in 6 out
      of 35 patients. Anti-HBs titer was significantly lower in the patients in whom
      HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24
      168.50) mIU/ml vs 99.94 (range 0.00-5342.98) mIU/ml, respectively (p = 0.036).
      Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned
      negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died
      due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia.
      Significant elevation of aminotransferase was found in only 1 patient, but HBsAg
      converted to positive in 2 patients and HBeAg converted to positive in 1 patient.
      CONCLUSION: Reactivation of resolved HBV can occur during standard
      immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti
      HBs may carry its risk.

PMID- 21844147
TI  - Cystatin C, renal function, and atherosclerosis in rheumatoid arthritis.
AB  - OBJECTIVE: We examined the hypothesis that cystatin C, a novel marker of renal
      function, is elevated in rheumatoid arthritis (RA) and is associated with
      inflammation and coronary atherosclerosis. METHODS: We measured serum cystatin C,
      creatinine, tumor necrosis factor-alpha and interleukin 6 concentrations,
      coronary artery calcium score (CACS), and Modified Diet in Renal Disease
      estimated glomerular filtration rate in 167 patients with RA and 91 controls.
      RESULTS: Cystatin C was higher in RA patients [median (IQR) 1.16 (0.99-1.35)
      mg/l] than controls [1.01 (0.90-1.19) mg/l; p < 0.001] and correlated positively
      with erythrocyte sedimentation rate (p < 0.001), C-reactive protein (p = 0.01),
      28-joint Disease Activity Score (p = 0.006), and Framingham risk score (FRS; p =
      0.02). Cystatin C was correlated with CACS (p < 0.001) in RA, but this was not
      significant after adjustment for age, race, sex, and FRS (p = 0.44). CONCLUSION:
      Cystatin C concentrations are higher in RA than controls and may reflect
      inflammation and undetected subclinical renal dysfunction. Cystatin C provides
      information regarding the risk of atherosclerosis in RA, but this is not
      independent of the information provided by conventional cardiovascular risk
      factors.

PMID- 21844148
TI  - Clinical and serological hallmarks of systemic sclerosis overlap syndromes.
AB  - OBJECTIVE: To determine the prevalence of systemic sclerosis (SSc) overlap
      syndrome and autoantibody profile in a large single-center cohort. METHODS: SSc
      diagnoses, subsets, and autoantibody profiles were obtained from clinical records
      of patients attending the Centre for Rheumatology, Royal Free Hospital, between
      September 1999 and February 2007. RESULTS: In total, 332 (20%) of 1700 patients
      with SSc had overlap syndrome. This comprised myositis (42.8%), rheumatoid
      arthritis (RA; 32%), Sjogren's syndrome (SS; 16.8%), and systemic lupus
      erythematosus (SLE; 8.4%). Antinuclear antibody was positive in 96.6% of
      patients. Anticentromere antibody (ACA) was exclusively present in limited
      cutaneous SSc (lcSSc) overlap cases (22%), and more common in SSc/SS overlap
      (44.7%), whereas no difference was found in the prevalence of Scl-70 autoantibody
      between lcSSc and diffuse cutaneous SSc overlap groups. U1RNP was more frequent
      in SSc/SLE (44%), while Ro antibody was more likely to be found in SSc/SS
      (29.8%). ACA was absent and anti-Scl-70 was infrequent in SSc/myositis;
      polymyositis-scleroderma antibody was more frequent in this group (33.1%). About
      50% of patients had raised rheumatoid factor (RF), with no difference between
      overlap groups irrespective of RF titer. In contrast, anticyclic citrullinated
      peptide antibody was more frequent in patients with RA features. CONCLUSION:
      About one-fifth of SSc cases had overlap features. There were distinct
      serological features that may predict specific clinical presentation and disease
      course.

PMID- 21844149
TI  - Incidence of tuberculosis among korean patients with ankylosing spondylitis who
      are taking tumor necrosis factor blockers.
AB  - OBJECTIVE: To assess the incidence and relative risk of new tuberculosis (TB)
      infections in Korean patients with ankylosing spondylitis (AS) and patients with
      AS who are undergoing treatment with tumor necrosis factor (TNF) blockers.
      METHODS: New cases of TB were identified by reviewing the medical records of 919
      patients with AS not treated with TNF blockers and those of 354 patients with AS
      treated with adalimumab (n = 66), infliximab (n = 78), or etanercept (n = 210)
      between 2002 and 2009. Reference data were obtained from the Korean National
      Tuberculosis Association. RESULTS: The mean incidence rate of TB was 69.8 per
      100,000 person-years (PY) in the general population, 308 per 100,000 PY in the
      TNF blocker-naive AS cohort, and 561 per 100,000 PY in the TNF blocker-exposed AS
      cohort. The incidence rate of TB in the infliximab-treated AS cohort (540 per
      100,000 PY) was higher than that in the adalimumab-treated AS cohort (490 per
      100,000 PY). No cases of TB occurred in the etanercept-treated AS cohort.
      Comparing the relative risks of TB infections between the TNF blocker-exposed AS
      cohort and the TNF blocker-naive AS cohort, no statistically significant
      difference was identified (risk ratio 0.53; 95% CI 0.144-1.913). CONCLUSION: The
      risk of TB was higher in the TNF blocker-naive AS cohort than it was in the
      general population. However, the risk of TB was not increased in the TNF blocker
      exposed AS cohort compared with the TNF blocker-naive AS cohort. Among patients
      with AS, etanercept is associated with a lower risk of TB compared with
      monoclonal antibodies.

PMID- 21844151
TI  - Tumor necrosis factor-blocking agents for children with enthesitis-related
      arthritis--data from the dutch arthritis and biologicals in children register,
      1999-2010.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of biological agents in
      children with enthesitis-related arthritis (ERA). METHODS: All patients with ERA
      in whom a biological agent was initiated between 1999 and 2010 were selected from
      the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing
      multicenter observational register, data on the course of the disease and
      medication use are retrieved prospectively at the start of the biological agent,
      after 3 months, and yearly thereafter. Inactive disease was assessed in
      accordance with the Wallace criteria. RESULTS: Twenty-two patients with ERA
      started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab
      (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched
      from etanercept to infliximab). Characteristics: 77% were male, 77% had
      enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4
      12.0) years; median followup from the start of the biological agent was 1.2 (IQR
      0.5-2.4) years. Intention-to-treat analysis shows that inactive disease was
      achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after
      15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients
      discontinued etanercept because of ineffectiveness, and switched to adalimumab
      (inactive disease achieved) or infliximab (decline in joints with arthritis after
      3 months of treatment). One patient discontinued etanercept because of remission,
      but had flare and restarted treatment, with good clinical response. No serious
      adverse events occurred. CONCLUSION: Tumor necrosis factor (TNF)-blocking agents
      seem effective and safe for patients with ERA that was previously unresponsive to
      1 or more DMARD. However, a sustained disease-free state could not be achieved,
      and none discontinued TNF-blocking agents successfully.

PMID- 21844150
TI  - Associations of vitamin d binding protein gene polymorphisms with the development
      of peripheral arthritis and uveitis in ankylosing spondylitis.
AB  - OBJECTIVE: Genetic factors account for more than 90% of overall susceptibility to
      ankylosing spondylitis (AS), and recent studies have focused on non-major
      histocompatibility complex genes. Vitamin D binding protein (DBP) is a highly
      polymorphic protein that transports vitamin D and its metabolites. In addition to
      its sterol binding capacity, DBP has many other roles in the inflammatory and
      immune systems, and has been reported to be associated with autoimmune diseases.
      We investigated the association between DBP polymorphisms and susceptibility to
      AS. METHODS: This case-control study was conducted in 223 patients with AS and
      239 ethnically matched controls who were genotyped for 8 single-nucleotide
      polymorphisms (SNP) in the DBP and its promoter. Genomic DNA was isolated from
      peripheral blood leukocytes using the standard phenolchloroform method, and the
      GoldenGate assay was used for genotyping. RESULTS: No significant association was
      found between the susceptibility to AS and DBP polymorphisms. In a subgroup
      analysis of patients with AS, G alleles at rs222016 and rs222020 (OR 0.63, 95% CI
      0.42-0.95, p = 0.03; OR 0.63, 95% CI 0.42-0.95, p = 0.03, respectively) and A
      allele at rs3733359 (OR 0.59, 95% CI 0.39-0.90, p = 0.01) showed the decreased
      risk of peripheral arthritis. G allele at rs4752 showed increased risk of uveitis
      (OR 2.04, 95% CI 1.12-3.72, p = 0.02). On the haplotype analyses, haplotype 2
      (AGGA) protected against the development of peripheral arthritis (p = 0.01) and
      haplotype 3 (GAAG) was associated with an increased likelihood of uveitis (p =
      0.02). CONCLUSION: DBP gene polymorphisms are associated with the development of
      peripheral arthritis and uveitis in Korean patients with AS. Given the influence
      of different DBP variants on the immune system, larger-scale studies are
      warranted to elucidate the role of DBP in the pathogenesis of AS.

PMID- 21844152
TI  - Treatment of mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: a
      retrospective clinical study.
AB  - OBJECTIVE: To retrospectively analyze the clinical course of patients with mucosa
      associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and
      associated Sjogren's syndrome (SS). METHODS: All consecutive patients with SS and
      MALT lymphoma (MALT-SS) diagnosed in the University Medical Center Groningen
      between January 1997 and January 2009 were analyzed. Clinical course and
      treatment outcome of SS and MALT lymphoma were evaluated. RESULTS: From a total
      of 329 patients with SS, 35 MALT-SS patients were identified, with a median
      followup of 76 months (range 16-153 mo). MALT lymphoma was localized in the
      parotid gland in all cases. Treatment consisted of "watchful waiting" (n = 10),
      surgery (n = 3), radiotherapy (n = 1), surgery combined with radiotherapy (n =
      2), rituximab only (n = 13), or rituximab combined with chemotherapy (n = 6).
      Complete response was observed in 14 patients, partial response in 1 patient, and
      stable disease in 20 patients. In 6 of 7 patients with initially high SS disease
      activity (M-protein, cryoglobulins, IgM rheumatoid factor > 100 KIU/l, severe
      extraglandular manifestations), MALT lymphoma progressed and/or SS disease
      activity increased after a median followup of 39 months (range 4-98 mo),
      necessitating retreatment. Only 1 patient with MALT who had low SS disease
      activity showed progression of lymphoma when left untreated. CONCLUSION: An
      initially high SS disease activity likely constitutes an adverse prognostic
      factor for progression of lymphoma and/or SS. Such patients may require treatment
      for both MALT lymphoma and SS. In SS patients with localized asymptomatic MALT
      lymphoma and low SS disease activity, a "watchful waiting" strategy seems
      justified.

PMID- 21844153
TI  - Is small artery elasticity decreased prior to intima-media thickening in patients
      with longstanding rheumatoid arthritis?
AB  - OBJECTIVE: To determine small artery elasticity (SAE) in patients with
      longstanding rheumatoid arthritis (RA) in comparison to healthy controls, and to
      investigate its relation to markers of endothelial cell activation, disease
      activity, joint damage, and the presence of atherosclerosis. METHODS: Forty-nine
      patients with RA and 50 age- and sex-matched healthy controls were studied.
      Traditional cardiovascular risk factors and disease-related factors were
      recorded. SAE was measured noninvasively by pulse-wave analysis (PWA).
      Endothelial activation was assessed by measuring levels of soluble vascular cell
      adhesion molecule-1 (sVCAM-1) and von Willebrand factor (vWF). Carotid intima
      media thickness (IMT), as an indicator of subclinical atherosclerosis, was
      assessed using ultrasonography. RESULTS: Patients with RA had higher body mass
      index, blood pressure, and triglyceride levels and were more often cigarette
      smokers compared to controls. SAE was decreased in RA patients compared to
      controls and was inversely related with age, smoking, blood pressure, vWF, sVCAM
      1, high sensitivity C-reactive protein, and IMT. Presence of RA was independently
      related to SAE in multivariate linear regression analysis. SAE was inversely
      related with the Health Assessment Questionnaire score. No correlation was found
      between SAE and other disease activity markers and damage. IMT in patients and
      controls was not different. CONCLUSION: Small artery elasticity was decreased in
      patients with longstanding RA. The presence of RA was independently associated
      with SAE. Whereas IMT in patients with RA was not increased, we hypothesize that
      endothelial dysfunction, reflected by decreased SAE, is present prior to IMT
      thickening in these patients.

PMID- 21844154
TI  - Biologic disease-modifying drug treatment patterns and associated costs for
      patients with rheumatoid Arthritis.
AB  - OBJECTIVE: To assess the influence of biologic treatment patterns on healthcare
      costs for patients with rheumatoid arthritis (RA) initiating tumor necrosis
      factor-alpha (TNF-alpha) antagonist therapy. METHODS: Patients with 2 RA
      diagnoses (International Classification of Diseases, 9th ed, 714.xx), and without
      psoriasis or Crohn's disease, were identified in a US employer-based insurance
      claims database. A sample of 2545 was constructed based on an index event of
      initiating TNF-alpha antagonist therapy and 30 months of continuous enrollment.
      Baseline characteristics were assessed in the 6-month pre-index period and
      treatment patterns were determined during the 12-month post-index period. Medical
      service and prescription drug costs were analyzed for Months 13-24 using
      multivariate regression analysis to control for baseline characteristics and time
      varying confounding associated with treatment and disease severity. RESULTS: In
      the first year after TNF-alpha initiation, 89% used a single TNF-alpha
      antagonist; only 9% and 2% had switched TNF-alpha antagonists or received non-TNF
      biologic disease-modifying antirheumatic drugs, respectively. Descriptive
      analyses revealed pairwise differences between groups (p < 0.05) in baseline
      characteristics (comorbidities, RA-related procedure use, and prescription drug
      use). Controlling for observed baseline characteristics, costs were greater for
      those treated with multiple vs single TNF-alpha antagonists: annual RA-related
      prescription drug costs ($8,340 vs $7,058; p = 0.012), RA-related healthcare
      costs ($15,048 vs $13,312; p = 0.008), and total healthcare costs ($26,697 vs
      $21,381; p < 0.001). CONCLUSION: In this sample, the majority of patients with RA
      were treated with a single TNF-alpha antagonist over the first year on therapy.
      For those who switched therapy, Year 2 RA-related and total direct healthcare
      costs were higher, adjusting for claims-based measures of RA disease severity.

PMID- 21844155
TI  - Recurrent postural vasovagal syncope: sympathetic nervous system phenotypes.
AB  - BACKGROUND: The pathophysiology of vasovagal syncope is poorly understood, and
      the treatment usually ineffective. Our clinical experience is that patients with
      vasovagal syncope fall into 2 groups, based on their supine systolic blood
      pressure, which is either normal (>100 mm Hg) or low (70-100 mm Hg). We
      investigated neural circulatory control in these 2 phenotypes. METHODS AND
      RESULTS: Sympathetic nervous testing was at 3 levels: electric, measuring
      sympathetic nerve firing (microneurography); neurochemical, quantifying
      norepinephrine spillover to plasma; and cellular, with Western blot analysis of
      sympathetic nerve proteins. Testing was done during head-up tilt (HUT),
      simulating the gravitational stress of standing, in 18 healthy control subjects
      and 36 patients with vasovagal syncope, 15 with the low blood pressure phenotype
      and 21 with normal blood pressure. Microneurography and norepinephrine spillover
      increased significantly during HUT in healthy subjects. The microneurography
      response during HUT was normal in normal blood pressure and accentuated in low
      blood pressure phenotype (P=0.05). Norepinephrine spillover response was
      paradoxically subnormal during HUT in both patient groups (P=0.001), who thus
      exhibited disjunction between nerve firing and neurotransmitter release; this
      lowered norepinephrine availability, impairing the neural circulatory response.
      Subnormal norepinephrine spillover in low blood pressure phenotype was linked to
      low tyrosine hydroxylase (43.7% normal, P=0.001), rate-limiting in norepinephrine
      synthesis, and in normal blood pressure to increased levels of the norepinephrine
      transporter (135% normal, P=0.019), augmenting transmitter reuptake. CONCLUSIONS:
      Patients with recurrent vasovagal syncope, when phenotyped into 2 clinical groups
      based on their supine blood pressure, show unique sympathetic nervous system
      abnormalities. It is predicted that future therapy targeting the specific
      mechanisms identified in the present report should translate into more effective
      treatment.

PMID- 21844156
TI  - Characterization of fractionated atrial electrograms critical for maintenance of
      atrial fibrillation: a randomized, controlled trial of ablation strategies (the
      CFAE AF trial).
AB  - BACKGROUND: Whether ablation of complex fractionated atrial electrograms (CFAE)
      modifies atrial fibrillation (AF) by eliminating drivers or atrial debulking
      remains unknown. This randomized study aimed to determine the effect of ablating
      different CFAE morphologies compared with normal electrograms (ie, debulking
      normal tissue) on the cycle length of persistent AF (AFCL). METHODS AND RESULTS:
      After pulmonary vein isolation left and right atrial CFAE were targeted, until
      termination of AF or abolition of CFAE before DC cardioversion. Ten-second
      electrograms were classified according to a validated scale, with grade 1 being
      most fractionated and grade 5 normal. Patients were randomly assigned to have
      CFAE grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1
      (group 2). An increase in AFCL (mean of left and right atrial appendage) >=5 ms
      after a lesion was regarded as significant. CFAE (n=968) were targeted in 20
      patients. AFCL increased after targeting 51+/-35% of grade 1 CFAE, 30+/-15% grade
      2, 12+/-5% grade 3, 33+/-12% grade 4, and 8+/-15% grade 5 CFAE (P<0.01 for grades
      1, 2, and 4 versus 5; 3 versus 5, not significant). The proportion of lesions
      causing AFCL prolongation was unaffected by the order in which CFAE were
      targeted. CONCLUSIONS: Targeting CFAE is not simply atrial debulking. Ablating
      certain grades of CFAE increases AFCL, suggesting they are more important in
      maintaining AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00894400.

PMID- 21844157
TI  - Acute altitude illnesses.

PMID- 21844158
TI  - Opportunistic chlamydia screening in a general practice consultation.

PMID- 21844159
TI  - Surrogates under scrutiny: fallible correlations, fatal consequences.

PMID- 21844161
TI  - Nature group journal retracts two papers after cancer researcher was found to
      have falsified data.

PMID- 21844164
TI  - Crucial part of US health reform act is unconstitutional, says appeal court.

PMID- 21844165
TI  - Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+
      monocytes.
AB  - Tim-3 and PD-1 are powerful immunoinhibitory molecules involved in immune
      tolerance, autoimmune responses, and antitumor or antiviral immune evasion. A
      current model for Tim-3 regulation during immune responses suggests a divergent
      function, such that Tim-3 acts synergistically with TLR signaling pathways in
      innate immune cells to promote inflammation, yet the same molecule terminates Th1
      immunity in adaptive immune cells. To better understand how Tim-3 might be
      functioning in innate immune responses, we examined the kinetics of Tim-3
      expression in human CD14+ M/M(F) in relation to expression of IL-12, a key
      cytokine in the transition of innate to adaptive immunity. Here, we show that Tim
      3 is constitutively expressed on unstimulated peripheral blood CD14+ monocytes
      but decreases rapidly upon TLR stimulation. Conversely, IL-12 expression is low
      in these cells but increases rapidly in CD14+ M/M(F) in correlation with the
      decrease in Tim-3. Blocking Tim-3 signaling or silencing Tim-3 expression led to
      a significant increase in TLR-mediated IL-12 production, as well as a decrease in
      activation-induced up-regulation of the immunoinhibitor, PD-1; TNF-alpha
      production was not altered significantly, but IL-10 production was increased.
      These results suggest that Tim-3 has a role as a regulator of pro- and anti
      inflammatory innate immune responses.

PMID- 21844167
TI  - The influence of spatial orientation on the perceived path of visual saltatory
      motion.
AB  - Visual saltation is the illusory mislocalization that occurs when multiple
      elements are rapidly presented to two peripheral locations; mislocalized elements
      appear to fill in the intermediate space. We investigated the influence of
      element orientation on the path of illusory saltatory motion. Experiment 1 showed
      that congruence in element orientation at the two locations (horizontal
      horizontal or vertical-vertical) produced rectilinear saltation, while
      incongruent orientations (vertical-horizontal or horizontal-vertical) elicited
      curvilinear saltation consistent with rigid rotation around a common point. In
      curvilinear saltation, mislocalized elements were perceived with an intermediate
      orientation. Experiment 2 showed that the perceived shape of the motion path was
      directly dependent on the salience of orientation information. In Experiment 3,
      we showed that the circular path of curvilinear saltation (induced by orientation
      incongruence) is altered by background motion (wedge-shaped regions of inward and
      outward moving dots) that overlaps only with the inter-element space. An
      ellipsoid path, where the major axis corresponds to the mislocalized element
      overlapping with outward motion and the minor axis corresponds to the
      mislocalized element overlapping with inward motion, is produced. These findings
      reveal that the interpretation of visual saltation arises from high-level
      computations in which the percept is derived through an interaction of form and
      motion.

PMID- 21844166
TI  - TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes.
AB  - IFN-I are pleiotropic cytokines that impact innate and adaptive immune responses.
      In this article, we discuss TLR7/9 versus TLR3/MDA5 signaling in antiviral
      responses and diabetes. pDCs are thought to have a critical role in antiviral
      defense because of their ability to rapidly secrete large amounts of IFN-I
      through TLR7/9 signaling. A recent study demonstrates that although pDCs are a
      source of IFN-I in vivo, their overall contribution to viral containment is
      limited and time-dependent, such that additional cellular sources of IFN-I are
      required to fully control viral infections. dsRNA sensors, such as TLR3 and MDA5,
      provide another important trigger for antiviral IFN-I responses, which can be
      exploited to enhance immune responses to vaccines. In the absence of infection,
      IFN-I production by pDCs or from signaling through dsRNA sensors has been
      implicated in the pathogenesis of autoimmune diseases such as diabetes. However,
      recent data demonstrate that IFN-I production via TLR3 and MDA5 is critical to
      counter diabetes caused by a virus with preferential tropism for pancreatic beta
      cells. This highlights the complexity of the host antiviral response and how
      multiple cellular and molecular components balance protective versus pathological
      responses.

PMID- 21844170
TI  - Teleconsultation via the web: an analysis of the type of questions that Iranian
      patients ask.
AB  - We evaluated an ask-the-doctor service which was set up as one of the accessory
      services of a health education website in Iran. The study lasted for five months.
      A total of 500 enquiries were submitted to the question and answer system. Eighty
      enquiries were excluded because they were duplicated submissions, not replied to
      by doctors or gave insufficient information for a reply. Most enquirers (33%)
      were female and aged 21-35 years. The most frequently asked questions were about
      embarrassing and sensitive topics, particularly on women's health and mental
      health. The majority of the questions were submitted on behalf of the enquirers
      themselves, with only 13% asking for others (children, parents, friends).
      Although there are various problems associated with online consultation, it does
      at least overcome one of the great drawbacks of some cultures, where people are
      reluctant to talk openly about certain matters, even with their doctors.

PMID- 21844171
TI  - Evaluation of teledermatology adoption by health-care professionals using a
      modified Technology Acceptance Model.
AB  - We examined the main factors affecting the intention of physicians to use
      teledermatology using a modified Technology Acceptance Model (TAM). The
      investigation was carried out during a teledermatology pilot study conducted in
      Spain. A total of 276 questionnaires were sent to physicians by email and 171
      responded (62%). Cronbach's alpha was acceptably high for all constructs.
      Theoretical variables were well correlated with each other and with the dependent
      variable (Intention to Use). Logistic regression indicated that the original TAM
      model was good at predicting physicians' intention to use teledermatology and
      that the variables Perceived Usefulness and Perceived Ease of Use were both
      significant (odds ratios of 8.4 and 7.4, respectively). When other theoretical
      variables were added, the model was still significant and it also became more
      powerful. However, the only significant predictor in the modified model was
      Facilitators with an odds ratio of 9.9. Thus the TAM was good at predicting
      physicians' intention to use teledermatology. However, the most important
      variable was the perception of Facilitators to using the technology (e.g.
      infrastructure, training and support).

PMID- 21844172
TI  - Evidence of benefit from telerehabilitation in routine care: a systematic review.
AB  - We systematically reviewed the evidence on the effectiveness of
      telerehabilitation (TR) applications. The review included reports on
      rehabilitation for any disability, other than mental health conditions, and drug
      or alcohol addiction. All forms of telecommunications technology for TR and all
      types of study design were considered. Study quality was assessed using an
      approach that considered both study performance and study design. Judgements were
      made on whether each TR application had been successful, whether reported
      outcomes were clinically significant, and whether further data were needed to
      establish the application as suitable for routine use. Sixty-one scientifically
      credible studies that reported patient outcomes or administrative changes were
      identified through computerized literature searches on five databases. Twelve
      clinical categories were covered by the studies. Those dealing with cardiac or
      neurological rehabilitation were the most numerous. Thirty-one of the studies
      (51%) were of high or good quality. Study results showed that 71% of the TR
      applications were successful, 18% were unsuccessful and for 11% the status was
      unclear. The reported outcomes for 51% of the applications appeared to be
      clinically significant. Poorer-quality studies tended to have worse outcomes than
      those from high- or good-quality studies. We judged that further study was
      required for 62% of the TR applications and desirable for 23%. TR shows promise
      in many fields, but compelling evidence of benefit and of impact on routine
      rehabilitation programmes is still limited. There is a need for more detailed,
      better-quality studies and for studies on the use of TR in routine care.

PMID- 21844169
TI  - Proteostasis and movement disorders: Parkinson's disease and amyotrophic lateral
      sclerosis.
AB  - Parkinson's disease (PD) is a movement disorder that afflicts over one million in
      the U.S.; amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is less
      prevalent but also has a high incidence. The two disorders sometimes present
      together, making a comparative study of interest. Both ALS and PD are
      neurodegenerative diseases, and are characterized by the presence of
      intraneuronal inclusions; however, different classes of neurons are affected and
      the primary protein in the inclusions differs between the diseases, and in some
      cases is different in distinct forms of the same disease. These observations
      might suggest that the more general approach of proteostasis pathway alteration
      would be a powerful one in treating these disorders. Examining results from human
      genetics and studies in model organisms, as well as from biochemical and
      biophysical characterization of the proteins involved in both diseases, we find
      that most instances of PD can be considered as arising from the misfolding, and
      self-association to a toxic species, of the small neuronal protein alpha
      synuclein, and that proteostasis strategies are likely to be of value for this
      disorder. For ALS, the situation is much more complex and less clear-cut; the
      available data are most consistent with a view that ALS may actually be a family
      of disorders, presenting similarly but arising from distinct and nonoverlapping
      causes, including mislocalization of some properly folded proteins and
      derangement of RNA quality control pathways. Applying proteostasis approaches to
      this disease may require rethinking or broadening the concept of what
      proteostasis means.

PMID- 21844173
TI  - Trial of a mobile phone method for recording dietary intake in adults with type 2
      diabetes: evaluation and implications for future applications.
AB  - We evaluated a mobile phone application (Nutricam) for recording dietary intake.
      It allowed users to capture a photograph of food items before consumption and
      store a voice recording to explain the contents of the photograph. This
      information was then sent to a website where it was analysed by a dietitian. Ten
      adults with type 2 diabetes (BMI 24.1-47.9 kg/m(2)) recorded their intake over a
      three-day period using both Nutricam and a written food diary. Compared to the
      food diary, energy intake was under-recorded by 649 kJ (SD 810) using the mobile
      phone method. However, there was no trend in the difference between dietary
      assessment methods at levels of low or high energy intake. All subjects reported
      that the mobile phone system was easy to use. Six subjects found that the time
      taken to record using Nutricam was shorter than recording using the written
      diary, while two reported that it was about the same. The level of detail
      provided in the voice recording and food items obscured in photographs reduced
      the quality of the mobile phone records. Although some modifications to the
      mobile phone method will be necessary to improve the accuracy of self-reported
      intake, the system was considered an acceptable alternative to written records
      and has the potential to be used by adults with type 2 diabetes for monitoring
      dietary intake by a dietitian.

PMID- 21844168
TI  - COPI budding within the Golgi stack.
AB  - The Golgi serves as a hub for intracellular membrane traffic in the eukaryotic
      cell. Transport within the early secretory pathway, that is within the Golgi and
      from the Golgi to the endoplasmic reticulum, is mediated by COPI-coated vesicles.
      The COPI coat shares structural features with the clathrin coat, but differs in
      the mechanisms of cargo sorting and vesicle formation. The small GTPase Arf1
      initiates coating on activation and recruits en bloc the stable heptameric
      protein complex coatomer that resembles the inner and the outer shells of
      clathrin-coated vesicles. Different binding sites exist in coatomer for membrane
      machinery and for the sorting of various classes of cargo proteins. During the
      budding of a COPI vesicle, lipids are sorted to give a liquid-disordered phase
      composition. For the release of a COPI-coated vesicle, coatomer and Arf cooperate
      to mediate membrane separation.

PMID- 21844174
TI  - The feasibility of videoconferencing for neuropsychological assessments of rural
      youth experiencing early psychosis.
AB  - We conducted a pilot study of the feasibility of videoconferencing as a mode of
      neuropsychological assessment in young people (14-30 years) from a rural area of
      New South Wales experiencing early psychosis. All participants (n = 11) completed
      assessments both face-to-face and by videoconference at a bandwidth of 384
      kbit/s. Assessments included confirmation of diagnosis, quality of life and
      neurocognitive functioning. There was a strong correlation between modes of
      assessment for most instruments. Bland-Altman plots indicated that in general the
      mean difference between face-to-face and videoconference modes of assessment was
      close to zero with significant bias only evident for general cognitive
      functioning (WTAR), where videoconferencing produced higher ratings than face-to
      face assessments. Feedback from the participants indicated strong acceptability
      of assessment by videoconferencing, thus supporting further investigation of use
      of this mode of assessment for clinical and research purposes.

PMID- 21844175
TI  - HIV-positive patients in Botswana state that mobile teledermatology is an
      acceptable method for receiving dermatology care.

PMID- 21844176
TI  - Automated home telephone self-monitoring reduces hospitalization in patients with
      advanced heart failure.
AB  - We studied 138 patients admitted for heart failure (HF). Patients were allocated
      one of three treatment strategies. Group 1 (G1, n = 50) were given usual care for
      HF, Group 2 (G2, n = 56) received a multi-disciplinary team approach, while Group
      3 (G3, n = 32) had home telephone self-monitoring. Telemonitoring was based on
      the answers to three simple queries about bodyweight change, dyspnoea and general
      health. The system stratified the HF severity of each patient once a week, and
      recommended a prompt medical appointment or simple follow-up. Over a 12-month
      follow-up period, there were 43 adverse events (cardiovascular deaths and
      rehospitalizations for HF: G1 = 22, G2 = 14, G3 = 7). There was no difference
      between G2 and G3 (P = 0.78) but there was significant disadvantage with usual
      care (P = 0.02 vs. G2 and P = 0.04 vs. G3). Time to re-admission for HF increased
      in G2 and G3 compared to G1 (188 and 198 days vs. 95 days, P = 0.03 and P = 0.02
      respectively). Automated home telephone self-monitoring reduced rehospitalization
      in patients with advanced HF.

PMID- 21844177
TI  - Smartphone applications for pain management.
AB  - Smartphone applications (or apps) are becoming increasingly popular. The lack of
      regulation or guidance for health-related apps means that the validity and
      reliability of their content is unknown. We have conducted a review of available
      apps relating to the generic condition of pain. The official application stores
      for five major smartphone platforms were searched: iPhone, Android, Blackberry,
      Nokia/Symbian and Windows Mobile. Apps were included if they reported a focus on
      pain education, management or relief, and were not solely aimed at health-care
      professionals (HCPs). A total of 111 apps met the inclusion criteria. The
      majority of apps reviewed claimed some information provision or electronic manual
      component. Diary tracking of pain variables was also a common feature. There was
      a low level of stated HCP involvement in app development and content. Despite an
      increasing number of apps being released, the frequency of HCP involvement is not
      increasing. Pain apps appear to be able to promise pain relief without any
      concern for the effectiveness of the product, or for possible adverse effects of
      product use. In a population often desperate for a solution to distressing and
      debilitating pain conditions, there is considerable risk of individuals being
      misled.

PMID- 21844178
TI  - Perception, satisfaction and utilization of the VALUE home telehealth service.
AB  - We conducted a randomized controlled trial to evaluate the perception,
      satisfaction and utilization of a home telehealth service for frail elderly
      people living independently in their home communities. Control group subjects
      continued with their usual care and intervention group subjects were able to
      supplement their usual care with the use of a web portal. The web portal allowed
      videoconferencing and electronic messaging between home care nurses and clients,
      ordering health-related and home care services, access to health-related
      information and general access to the Internet. A total of 99 eligible people (59
      female, 40 male) from one urban and one rural study site agreed to participate in
      the study. Eighty-four subjects were active participants for nine months. There
      were no significant differences in perception of technology between the two
      groups at baseline. At 60-day follow-up, the intervention group was significantly
      more positive towards technology compared to their own baseline (P < 0.001) and
      compared to the 60-day scores for the controls (P < 0.001). The intervention
      group indicated that overall the telehealth service met their expectations (mean
      score 9 out of 10) and they would recommend it to others (mean score 9.5 out of
      10). All subjects were able to use the portal without difficulty after brief
      instructions from the nurses. A total of 1054 videoconferences were conducted
      with the intervention subjects. Fifty-six of these (5%) had to be discontinued
      after successful connection because of technical problems. Intervention subjects
      made fewer emergency department visits than control subjects, more visits to the
      eye doctor, fewer visits in all categories of home care utilization, and lower
      use of transportation services. Frail elderly people are able to adopt home
      telehealth technologies which may enable them to maintain independent living
      arrangements.

PMID- 21844179
TI  - Mobile computing and the quality of home care nursing practice.
AB  - We investigated the effects of the introduction of mobile computing on the
      quality of home care nursing practice in Quebec. The software, which structured
      and organized the nursing activities in patients' homes, was installed
      sequentially in nine community health centres. The completeness of the nursing
      notes was compared in 77 paper records (pre-implementation) and 73 electronic
      records (post-implementation). Overall, the introduction of the software was
      associated with an improvement in the completeness of the nursing notes. All 137
      nurse users were asked to complete a structured questionnaire. A total of 101
      completed questionnaires were returned (74% response rate). Overall, the nurses
      reported a very high level of satisfaction with the quality of clinical
      information collected. A total of 57 semi-structured interviews were conducted
      and most nurses believed that the new software represented a user-friendly tool
      with a clear and understandable structure. A postal questionnaire was sent to
      approximately 1240 patients. A total of 223 patients returned the questionnaire
      (approximately 18% response rate). Overall, patients felt that the use of mobile
      computing during home visits allowed nurses to manage their health condition
      better and, hence, provide superior care services. The use of mobile computing
      had positive and significant effects on the quality of care provided by home
      nurses.

PMID- 21844180
TI  - Managing suicidality in home-based telehealth.
AB  - We describe the case of a US veteran from the war in Afghanistan with post
      traumatic stress disorder (PTSD). The patient was undergoing treatment at home
      via telehealth as part of a research trial. In week six, he presented with severe
      suicidal ideation and required emergency hospitalization. Through a series of
      immediate enhanced communications (i.e. by videoconference) between the patient,
      patient's family, treatment team and local resources, the patient's symptoms were
      assessed to identify suicidality and an intervention was successfully carried
      out, involving the development of a safety plan and eventual transportation to an
      inpatient unit at the local Veterans Administration Medical Center, where he was
      hospitalized for three days. This demonstrates the value of telehealth in
      identifying and treating severe psychiatric symptoms in addition to supporting
      the safety of these procedures to address suicidality.

PMID- 21844181
TI  - A telepsychiatry transition clinic: the first 12 months experience.
AB  - To improve the management of soldiers with combat-related mental health problems,
      an interdisciplinary telepsychiatry service was established between a clinic at
      the Fort Bragg army base and the Veterans Affairs (VA) Medical Center in Salem.
      In the first 12 months of operation, 120 soldiers (105 males) were seen in a
      total of 394 telepsychiatry sessions. The time spent on telepsychiatry by the six
      VA psychiatrists increased from 13 hours in the first month to 41 hours in the
      twelfth month. The number of telepsychiatry sessions increased from nine in the
      first month to 56 in the twelfth month. The mean global assessment of function
      score (GAF) in the soldiers increased significantly (P < 0.001) from 58.0 at
      intake to 62.3 at the last visit. Soldiers received VA telepsychiatry on average
      22 days after the initial consultation with a primary care provider, a reduction
      of at least eight days compared to the previous delay. The majority of soldiers
      (89%) who were treated by VA psychiatrists enrolled in the VA within about six
      months of discharge. Similar VA-US Military collaborations may prove beneficial
      for other military bases that have returning combat soldiers.

PMID- 21844182
TI  - Challenges and opportunities for the adoption of telemedicine in India.

PMID- 21844183
TI  - Downregulation of RBMS3 is associated with poor prognosis in esophageal squamous
      cell carcinoma.
AB  - Deletions on chromosome 3p occur often in many solid tumors, including esophageal
      squamous cell carcinoma (ESCC), suggesting the existence at this location of one
      or more tumor suppressor genes (TSG). In this study, we characterized RBMS3 gene
      encoding an RNA-binding protein as a candidate TSG located at 3p24.
      Downregulation of RBMS3 mRNA and protein levels was documented in approximately
      50% of the primary ESCCs examined. Clinical association studies determined that
      RBMS3 downregulation was associated with poor clinical outcomes. RBMS3 expression
      effectively suppressed the tumorigenicity of ESCC cells in vitro and in vivo,
      including by inhibition of cell growth rate, foci formation, soft agar colony
      formation, and tumor formation in nude mice. Molecular analyses revealed that
      RBMS3 downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb
      phosphorylation. Together, our findings suggest a tumor suppression function for
      the human RBMS3 gene in ESCC, acting through c-Myc downregulation, with genetic
      loss of this gene in ESCC contributing to poor outcomes in this deadly disease.

PMID- 21844184
TI  - Cyclin D1 and cdk4 mediate development of neurologically destructive
      oligodendroglioma.
AB  - Although the molecular changes that characterize gliomas have been studied, the
      pathogenesis of tumor development remains unclear. p21 contributes to
      gliomagenesis by stabilizing cyclin D1-cdk4 kinase complexes, suggesting that
      cyclin D1 and cdk4 may also be required for glial tumor development. In this
      study, we used a mouse model to attempt to confirm this hypothesis, finding that
      cyclin D1 and cdk4 played active roles in not only the tumor but also the tumor
      microenvironment. Loss of cdk4 blocked tumor development, but loss of cyclin D1
      did not prevent gliomas from developing. Instead, loss of cyclin D1 impeded
      progression to higher stages of malignancy. Enforcing expression of cyclin D1 was
      insufficient to correct the progression defect observed in cyclin D1-deficient
      animals. In contrast, restoration of cdk4 in the cdk4-deficient animals restored
      cell proliferation and tumor formation, although at lower tumor grades. Notably,
      the failure of tumors in the cyclin D1- and cdk4-deficient animals to progress to
      higher grades was correlated with a failure to fully activate microglia in the
      tumor microenvironment. Moreover, when platelet-derived growth factor-transformed
      glial cells were engrafted orthotopically into the mice, the tumors that formed
      progressed to high grades in wild-type mice but not cyclin D1-deficient animals.
      Together, our findings establish that the cyclin D1-cdk4 axis is not only
      critical in glial tumor cells but also in stromal-derived cells in the
      surrounding tumor microenvironment that are vital to sustain tumor outgrowth.

PMID- 21844185
TI  - Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses
      radioiodide treatment.
AB  - Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a
      little characterized proto-oncogene that has been implicated in the etiology of
      breast and thyroid tumors. In this study, we created a murine transgenic model to
      target PBF expression to the thyroid gland (PBF-Tg mice) and found that these
      mice exhibited normal thyroid function, but a striking enlargement of the thyroid
      gland associated with hyperplastic and macrofollicular lesions. Expression of the
      sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of
      thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in
      PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures
      from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids
      exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators
      of thyrocyte proliferation, along with upregulation of the downstream
      proliferative marker cyclin D1. We extended and confirmed findings from the mouse
      model by examining PBF expression in human multinodular goiters (MNG), a
      hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated
      relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in
      human primary thyrocytes was sufficient to increase radioiodine uptake. Together,
      our findings indicate that overexpression of PBF causes thyroid cell
      proliferation, macrofollicular lesions, and hyperplasia, as well as repression of
      the critical therapeutic route for radioiodide uptake.

PMID- 21844188
TI  - Extinction partially reverts structural changes associated with remote fear
      memory.
AB  - Structural synaptic changes occur in medial prefrontal cortex circuits during
      remote memory formation. Whether extinction reverts or further reshapes these
      circuits is, however, unknown. Here we show that the number and the size of
      spines were enhanced in anterior cingulate (aCC) and infralimbic (ILC) cortices
      36 d following contextual fear conditioning. Upon extinction, aCC spine density
      returned to baseline, but the enhanced proportion of large spines did not.
      Differently, ILC spine density remained elevated, but the size of spines
      decreased dramatically. Thus, extinction partially erases the remote memory
      network, suggesting that the preserved network properties might sustain
      reactivation of extinguished conditioned fear.

PMID- 21844186
TI  - Common breast cancer susceptibility loci are associated with triple-negative
      breast cancer.
AB  - Triple-negative breast cancers are an aggressive subtype of breast cancer with
      poor survival, but there remains little known about the etiologic factors that
      promote its initiation and development. Commonly inherited breast cancer risk
      factors identified through genome-wide association studies display heterogeneity
      of effect among breast cancer subtypes as defined by the status of estrogen and
      progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC),
      22 common breast cancer susceptibility variants were investigated in 2,980
      Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We
      identified six single-nucleotide polymorphisms, including rs2046210 (ESR1),
      rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and
      rs8100241 (19p13.1), significantly associated with the risk of triple-negative
      breast cancer. Together, our results provide convincing evidence of genetic
      susceptibility for triple-negative breast cancer.

PMID- 21844187
TI  - Associative, bidirectional changes in neural signaling utilizing NMDA receptor-
      and endocannabinoid-dependent mechanisms.
AB  - Persistent, bidirectional changes in synaptic signaling (that is, potentiation
      and depression of the synapse) can be induced by the precise timing of individual
      pre- and postsynaptic action potentials. However, far less attention has been
      paid to the ability of paired trains of action potentials to elicit persistent
      potentiation or depression. We examined plasticity following the pairing of spike
      trains in the touch mechanosensory neuron (T cell) and S interneuron (S cell) in
      the medicinal leech. Long-term potentiation (LTP) of T to S signaling was
      elicited when the T-cell spike train preceded the S-cell train. An interval 0 to
      +1 sec between the T- and S-cell spike trains was required to elicit long-term
      potentiation (LTP), and this potentiation was NMDA receptor (NMDAR)-dependent.
      Long-term depression (LTD) was elicited when S-cell activity preceded T-cell
      activity and the interval between the two spike trains was -0.2 sec to -10 sec.
      This surprisingly broad temporal window involved two distinct cellular
      mechanisms; an NMDAR-mediated LTD (NMDAR-LTD) when the pairing interval was
      relatively brief (<-1 sec) and an endocannabinoid-mediated LTD (eCB-LTD) when
      longer pairing intervals were used (-1 to -10 sec). This eCB-LTD also required
      activation of a presynaptic transient receptor potential vanilloid (TRPV)-like
      receptor, presynaptic Ca(2+) release from intracellular stores and activation of
      voltage-gated Ca(2+) channels (VGCCs). These findings demonstrate that the
      pairing of spike trains elicits timing-dependent forms of LTP and LTD that are
      supported by a complex set of cellular mechanisms involving NMDARs and
      endocannabinoid activation of TRPV-like receptors.

PMID- 21844189
TI  - Intracellular erythrocyte platelet-activating factor acetylhydrolase I
      inactivates aspirin in blood.
AB  - Aspirin (acetylsalicylic acid) prophylaxis suppresses major adverse
      cardiovascular events, but its rapid turnover limits inhibition of platelet
      cyclooxygenase activity and thrombosis. Despite its importance, the identity of
      the enzyme(s) that hydrolyzes the acetyl residue of circulating aspirin, which
      must be an existing enzyme, remains unknown. We find that circulating aspirin was
      extensively hydrolyzed within erythrocytes, and chromatography indicated these
      cells contained a single hydrolytic activity. Purification by over 1400-fold and
      sequencing identified the PAFAH1B2 and PAFAH1B3 subunits of type I platelet
      activating factor (PAF) acetylhydrolase, a phospholipase A(2) with selectivity
      for acetyl residues of PAF, as a candidate for aspirin acetylhydrolase. Western
      blotting showed that catalytic PAFAH1B2 and PAFAH1B3 subunits of the type I
      enzyme co-migrated with purified erythrocyte aspirin hydrolytic activity.
      Recombinant PAFAH1B2, but not its family member plasma PAF acetylhydrolase,
      hydrolyzed aspirin, and PAF competitively inhibited aspirin hydrolysis by
      purified or recombinant erythrocyte enzymes. Aspirin was hydrolyzed by HEK cells
      transfected with PAFAH1B2 or PAFAH1B3, and the competitive type I PAF
      acetylhydrolase inhibitor NaF reduced erythrocyte hydrolysis of aspirin. Exposing
      aspirin to erythrocytes blocked its ability to inhibit thromboxane A(2) synthesis
      and platelet aggregation. Not all individuals or populations are equally
      protected by aspirin prophylaxis, the phenomenon of aspirin resistance, and
      erythrocyte hydrolysis of aspirin varied 3-fold among individuals, which
      correlated with PAFAH1B2 and not PAFAH1B3. We conclude that intracellular type I
      PAF acetylhydrolase is the major aspirin hydrolase of human blood.

PMID- 21844190
TI  - Quenching in Arabidopsis thaliana mutants lacking monomeric antenna proteins of
      photosystem II.
AB  - The minor light-harvesting complexes CP24, CP26, and CP29 have been proposed to
      play a key role in the zeaxanthin (Zx)-dependent high light-induced regulation
      (NPQ) of excitation energy in higher plants. To characterize the detailed roles
      of these minor complexes in NPQ and to determine their specific quenching effects
      we have studied the ultrafast fluorescence kinetics in knockout (ko) mutants
      koCP26, koCP29, and the double mutant koCP24/CP26. The data provide detailed
      insight into the quenching processes and the reorganization of the Photosystem
      (PS) II supercomplex under quenching conditions. All genotypes showed two NPQ
      quenching sites. Quenching site Q1 is formed by a light-induced functional
      detachment of parts of the PSII supercomplex and a pronounced quenching of the
      detached antenna parts. The antenna remaining bound to the PSII core was also
      quenched substantially in all genotypes under NPQ conditions (quenching site Q2)
      as compared with the dark-adapted state. The latter quenching was about equally
      strong in koCP26 and the koCP24/CP26 mutants as in the WT. Q2 quenching was
      substantially reduced, however, in koCP29 mutants suggesting a key role for CP29
      in the total NPQ. The observed quenching effects in the knockout mutants are
      complicated by the fact that other minor antenna complexes do compensate in part
      for the lack of the CP24 and/or CP29 complexes. Their lack also causes some LHCII
      dissociation already in the dark.

PMID- 21844191
TI  - Functional importance of covalent homodimer of reelin protein linked via its
      central region.
AB  - Reelin is a 3461-residue secreted glycoprotein that plays a critical role in
      brain development through its action on target neurons. Although it is known that
      functional reelin protein exists as multimer formed by interchain disulfide
      bond(s) as well as through non-covalent interactions, the chemical nature of the
      multimer assembly has been elusive. In the present study, we identified, among
      122 cysteines present in full-length reelin, the single critical cysteine residue
      (Cys(2101)) responsible for the covalent multimerization. C2101A mutant reelin
      failed to assemble into disulfide-bonded multimers, whereas it still exhibited
      non-covalently associated high molecular weight oligomeric states in solution.
      Detailed analysis of tryptic fragments produced from the purified reelin proteins
      revealed that the minimum unit of the multimer is a homodimeric reelin linked via
      Cys(2101) present in the central region and that this cysteine does not connect
      to the N-terminal region of reelin, which had been postulated as the primary
      oligomerization domain. A surface plasmon resonance binding assay confirmed that
      C2101A mutant reelin retained binding capability toward two neuronal receptors
      apolipoprotein E receptor 2 and very low density lipoprotein receptor. However,
      it failed to show signaling activity in the assay using the cultured neurons.
      These results indicate that an intact higher order architecture of reelin
      multimer maintained by both Cys(2101)-mediated homodimerization and other non
      covalent association present elsewhere in the reelin primary structure are
      essential for exerting its full biological activity.

PMID- 21844192
TI  - Receptor for advanced glycation end products (RAGE) prevents endothelial cell
      membrane resealing and regulates F-actin remodeling in a beta-catenin-dependent
      manner.
AB  - Receptor for advanced glycation end products (RAGE), an immunoglobin superfamily
      cell surface receptor, contributes to the vascular pathology associated with
      multiple disorders, including Alzheimer disease (AD), diabetic complications, and
      inflammatory conditions. However, the underlying mechanisms remain largely
      unclear. Here, using the human umbilical vein endothelial cell line (ECV-304)
      expressing human RAGE, we report that RAGE expression leads to an altered F-actin
      organization and impaired membrane resealing. To investigate the underlying
      mechanisms, we showed that RAGE expression increases beta-catenin level, which
      decreases F-actin stress fibers and attenuates plasma membrane resealing. These
      results thus suggest a negative function for RAGE in endothelial cell membrane
      repair and reveal a new mechanism underlying RAGE regulation of F-actin
      remodeling and membrane resealing.

PMID- 21844193
TI  - Differential oxidant tolerance determined by the key transcription factor Yap1 is
      controlled by levels of the Yap1-binding protein, Ybp1.
AB  - The Saccharomyces cerevisiae transcription factor Yap1 is a central determinant
      of oxidative stress tolerance. This protein is found primarily in the cytoplasm
      in the absence of oxidative stress but, upon exposure to oxidants, rapidly
      translocates to the nucleus and activates expression of target genes. Although
      both diamide and H(2)O(2) have been used to impose oxidative stress on cells,
      these different oxidants trigger Yap1 nuclear localization in distinctly
      different ways. Diamide appears to oxidize particular cysteine residues on Yap1,
      leading to inhibition of association of Yap1 with the nuclear exportin Crm1. Crm1
      would normally transport Yap1 out of the nucleus. H(2)O(2) activation of Yap1
      nuclear localization requires the participation of the glutathione peroxidase
      Gpx3 and the Yap1-binding protein Ybp1. H(2)O(2) exposure triggers formation of a
      dual disulfide bonded Yap1 that is catalyzed by the presence of Gpx3 and Ybp1. In
      the current study, we have determined that two distinct pools of Yap1 exist in
      the cell. These pools are designated by the level of Ybp1. Ybp1 interacts
      directly with Yap1 and these proteins form a stable complex in vivo. Genetic and
      biochemical experiments indicate that Ybp1 is rate-limiting for Yap1 oxidative
      folding during H(2)O(2) stress. The fungal pathogen Candida glabrata expresses a
      protein homologous to Ybp1 called CgYbp1. Overproduction of CgYbp1 elevated
      H(2)O(2) tolerance in this pathogen indicating that the determinative role of
      Ybp1 in setting the level of H(2)O(2) resistance has been evolutionarily
      conserved.

PMID- 21844194
TI  - Substrate tRNA recognition mechanism of a multisite-specific tRNA
      methyltransferase, Aquifex aeolicus Trm1, based on the X-ray crystal structure.
AB  - Archaeal and eukaryotic tRNA (N(2),N(2)-guanine)-dimethyltransferase (Trm1)
      produces N(2),N(2)-dimethylguanine at position 26 in tRNA. In contrast, Trm1 from
      Aquifex aeolicus, a hyper-thermophilic eubacterium, modifies G27 as well as G26.
      Here, a gel mobility shift assay revealed that the T-arm in tRNA is the binding
      site of A. aeolicus Trm1. To address the multisite specificity, we performed an x
      ray crystal structure study. The overall structure of A. aeolicus Trm1 is similar
      to that of archaeal Trm1, although there is a zinc-cysteine cluster in the C
      terminal domain of A. aeolicus Trm1. The N-terminal domain is a typical catalytic
      domain of S-adenosyl-l-methionine-dependent methyltransferases. On the basis of
      the crystal structure and amino acid sequence alignment, we prepared 30 mutant
      Trm1 proteins. These mutant proteins clarified residues important for S-adenosyl
      l-methionine binding and enabled us to propose a hypothetical reaction mechanism.
      Furthermore, the tRNA-binding site was also elucidated by methyl transfer assay
      and gel mobility shift assay. The electrostatic potential surface models of A.
      aeolicus and archaeal Trm1 proteins demonstrated that the distribution of
      positive charges differs between the two proteins. We constructed a tRNA-docking
      model, in which the T-arm structure was placed onto the large area of positive
      charge, which is the expected tRNA-binding site, of A. aeolicus Trm1. In this
      model, the target G26 base can be placed near the catalytic pocket; however, the
      nucleotide at position 27 gains closer access to the pocket. Thus, this docking
      model introduces a rational explanation of the multisite specificity of A.
      aeolicus Trm1.

PMID- 21844195
TI  - Engineering a prokaryotic Cys-loop receptor with a third functional domain.
AB  - Prokaryotic members of the Cys-loop receptor ligand-gated ion channel superfamily
      were recently identified. Previously, Cys-loop receptors were only known from
      multicellular organisms (metazoans). Contrary to the metazoan Cys-loop receptors,
      the prokaryotic ones consist of an extracellular (ECD) and a transmembrane domain
      (TMD), lacking the large intracellular domain (ICD) present in metazoa (between
      transmembrane segments M3 and M4). Using a chimera approach, we added the 115
      amino acid ICD from mammalian serotonin type 3A receptors (5-HT(3A)) to the
      prokaryotic proton-activated Gloeobacter violaceus ligand-gated ion channel
      (GLIC). We created 12 GLIC-5-HT(3A)-ICD chimeras by replacing a variable number
      of amino acids in the short GLIC M3M4 linker with the entire 5-HT(3A)-ICD. Two
      electrode voltage clamp recordings after expression in Xenopus laevis oocytes
      showed that only two chimeras were functional and produced currents upon
      acidification. The pH(50) was comparable with wild-type GLIC. 5-HT(3A) receptor
      expression can be inhibited by the chaperone protein RIC-3. We have shown
      previously that the 5-HT(3A)-ICD is required for the attenuation of 5-HT-induced
      currents when RIC-3 is co-expressed with 5-HT(3A) receptors in X. laevis oocytes.
      Expression of both functional 5-HT(3A) chimeras was inhibited by RIC-3 co
      expression, indicating appropriate folding of the 5-HT(3A)-ICD in the chimeras.
      Our results indicate that the ICD can be considered a separate domain that can be
      removed from or added to the ECD and TMD while maintaining the overall structure
      and function of the ECD and TMD.

PMID- 21844196
TI  - GTP-dependent binding and nuclear transport of RNA polymerase II by Npa3 protein.
AB  - We identified XAB1 in a proteomic screen for factors that interact with human RNA
      polymerase II (RNAPII). Because XAB1 has a conserved Saccharomyces cerevisiae
      homologue called Npa3, yeast genetics and biochemical analysis were used to
      dissect the significance of the interaction. Degron-dependent Npa3 depletion
      resulted in genome-wide transcription decreases, correlating with a loss of
      RNAPII from genes as measured by chromatin immunoprecipitation. Surprisingly,
      however, transcription in vitro was unaffected by Npa3, suggesting that it
      affects a process that is not required for transcription in yeast extracts.
      Indeed, Npa3 depletion in vivo affects nuclear localization of RNAPII; the
      polymerase accumulates in the cytoplasm. Npa3 is a member of the GPN-LOOP family
      of GTPases. Npa3 mutants that either cannot bind GTP or that bind but cannot
      hydrolyze it are inviable and unable to support nuclear transport of RNAPII.
      Surprisingly, we were unable to detect interactions between Npa3 and proteins in
      the classical importin alpha/beta pathway for nuclear import. Interestingly, Npa3
      RNAPII binding is significantly increased by the addition of GTP or its slowly
      hydrolyzable analogue guanosine 5'-3-O-(thio)triphosphate (GTPgammaS). Moreover,
      the Npa3 mutant that binds GTP, but cannot hydrolyze it, binds RNAPII even in the
      absence of added GTP, whereas the mutant that cannot bind GTP is unable to bind
      the polymerase. Together, our data suggest that Npa3 defines an unconventional
      pathway for nuclear import of RNAPII, which involves GTP-dependent binding of
      Npa3 to the polymerase.

PMID- 21844197
TI  - Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed
      rectifier potassium channels revealed by low K+-induced hERG endocytic
      degradation.
AB  - Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks))
      activating delayed rectifier potassium channels. The human ether-a-go-go-related
      gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks).
      Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder
      with a high risk of sudden death. A reduction in extracellular K(+) concentration
      ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature
      hERG channels from the plasma membrane. In the present study, we investigated
      whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our
      data show that when hERG and KCNQ1 were expressed separately in human embryonic
      kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the
      mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1
      were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction.
      Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+)
      conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1
      expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated
      with mature hERG channels that are localized in the plasma membrane. Biophysical
      and pharmacological analyses indicate that although hERG and KCNQ1 closely
      interact with each other, they form distinct hERG and KCNQ1 channels. These data
      extend our understanding of delayed rectifier potassium channel trafficking and
      regulation, as well as the pathology of LQTS.

PMID- 21844198
TI  - Several ADP-ribosylation factor (Arf) isoforms support COPI vesicle formation.
AB  - Newly synthesized proteins and lipids are transported in vesicular carriers along
      the secretory pathway. Arfs (ADP-ribosylation factors), a family of highly
      conserved GTPases within the Ras superfamily, control recruitment of molecular
      coats to membranes, the initial step of coated vesicle biogenesis. Arf1 and
      coatomer constitute the minimal cytosolic machinery leading to COPI vesicle
      formation from Golgi membranes. Although some functional redundancies have been
      suggested, other Arf isoforms have been poorly analyzed in this context. In this
      study, we found that Arf1, Arf4, and Arf5, but not Arf3 and Arf6, associate with
      COPI vesicles generated in vitro from Golgi membranes and purified cytosol. Using
      recombinant myristoylated proteins, we show that Arf1, Arf4, and Arf5 each
      support COPI vesicle formation individually. Unexpectedly, we found that Arf3
      could also mediate vesicle biogenesis. However, Arf3 was excluded from the
      vesicle fraction in the presence of the other isoforms, highlighting a functional
      competition between the different Arf members.

PMID- 21844199
TI  - c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or
      tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in
      mice.
AB  - Sustained JNK activation plays a critical role in hepatotoxicity by acetaminophen
      or GalN/TNF-alpha. To address the importance of JNK translocation to mitochondria
      that accompanies sustained activation in these models, we assessed the importance
      of the expression of a potential initial target of JNK in the outer membrane of
      mitochondria, namely Sab (SH3 domain-binding protein that preferentially
      associates with Btk), also known as Sh3bp5 (SH3 domain-binding protein 5).
      Silencing the expression of Sab in the liver using adenoviral shRNA inhibited
      sustained JNK activation and mitochondrial targeting of JNK and the upstream MKK4
      (MAPK kinase 4), accompanied by striking protection against liver injury in vivo
      and in cultured hepatocytes in both toxicity models. We conclude that
      mitochondrial Sab may serve as a platform for the MAPK pathway enzymes and that
      the interaction of stress-activated JNK with Sab is required for sustained JNK
      activation and toxicity.

PMID- 21844200
TI  - The small GTPase Cdc42 interacts with Niemann-Pick C1-like 1 (NPC1L1) and
      controls its movement from endocytic recycling compartment to plasma membrane in
      a cholesterol-dependent manner.
AB  - Niemann-Pick C1-like 1 (NPC1L1) is a multi-transmembrane protein that mediates
      the absorption of dietary and biliary cholesterol through vesicular endocytosis.
      The subcellular localization of NPC1L1 is regulated by cholesterol. Cholesterol
      depletion induces the transport of NPC1L1 to plasma membrane (PM) from endocytic
      recycling compartment that requires MyoVb.Rab11a.Rab11-FIP2 triple complex, and
      cholesterol-replenishment renders the internalization of NPC1L1 together with
      cholesterol. Here, we find that GTP-bound Cdc42 interacts with NPC1L1.
      Cholesterol depletion regulates the activation of Cdc42 and enhances NPC1L1-Cdc42
      interaction. Overexpression of constitutive GTP-bound Cdc42 mutant form or
      knockdown of Cdc42 inhibits the transport of NPC1L1 to the PM and disturbs the
      cholesterol-regulated binding of NPC1L1 to Rab11a, MyoVb, and actin. Knockdown of
      Cdc42 downstream effectors N-WASP or Arp3 also leads to the similar results. In
      liver-specific Cdc42 knock-out (Cdc42 LKO) mice, NPC1L1 fails to localize to bile
      canaliculi, and the biliary cholesterol cannot be efficiently reabsorbed. These
      results indicate that Cdc42 controls the cholesterol-regulated transport and
      localization of NPC1L1, and plays a role in cholesterol absorption.

PMID- 21844201
TI  - Single-stranded noncoding RNAs mediate local epigenetic alterations at gene
      promoters in rat cell lines.
AB  - A growing number of noncoding RNAs (ncRNAs) are thought to be involved in
      sequence-specific alterations of epigenetic processes, mostly causing gene
      repression. In this study, promoter-associated ncRNAs (pancRNAs >200 nucleotides
      in size) that were endogenously generated from the sense strand at Map2b,
      antisense strand at Nefl, and both strands at Vim were investigated regarding
      their epigenetic potential as positive or negative regulators in rat
      pheochromocytoma (PC12) and fibroblast (normal rat kidney) cell lines. The
      respective antisense pancRNAs were associated with several active chromatin marks
      at the Nefl and Vim promoters. Forced expression of fragments expressing the
      antisense pancRNAs caused sequence-specific DNA demethylation, whereas a decrease
      of expression induced methylation of the same sequences. In contrast, perturbing
      the expression of the two sense pancRNAs did not change the DNA methylation
      status. These results suggest that a fraction of naturally occurring ncRNAs acts
      in cis as a single-stranded form and that the transcriptional orientation of
      pancRNA is important for the establishment of sequence-specific epigenetic
      modifications consistent with open chromatin structure.

PMID- 21844202
TI  - GPIHBP1, an endothelial cell transporter for lipoprotein lipase.
AB  - Interest in lipolysis and the metabolism of triglyceride-rich lipoproteins was
      recently reignited by the discovery of severe hypertriglyceridemia
      (chylomicronemia) in glycosylphosphatidylinositol-anchored high density
      lipoprotein-binding protein 1 (GPIHBP1)-deficient mice. GPIHBP1 is expressed
      exclusively in capillary endothelial cells and binds lipoprotein lipase (LPL)
      avidly. These findings prompted speculation that GPIHBP1 serves as a binding site
      for LPL in the capillary lumen, creating "a platform for lipolysis." More recent
      studies have identified a second and more intriguing role for GPIHBP1-picking up
      LPL in the subendothelial spaces and transporting it across endothelial cells to
      the capillary lumen. Here, we review the studies that revealed that GPIHBP1 is
      the LPL transporter and discuss which amino acid sequences are required for
      GPIHBP1-LPL interactions. We also discuss the human genetics of LPL transport,
      focusing on cases of chylomicronemia caused by GPIHBP1 mutations that abolish
      GPIHBP1's ability to bind LPL, and LPL mutations that prevent LPL binding to
      GPIHBP1.

PMID- 21844203
TI  - Differential regulation of mast cell degranulation versus cytokine secretion by
      the actin regulatory proteins Coronin1a and Coronin1b.
AB  - Mast cell (MC) activation via aggregation of the high affinity IgE receptor
      (FcepsilonRI) causes degranulation and release of proinflammatory mediators in a
      process that involves the reorganization of the actin cytoskeleton. However, the
      regulatory pathways and the molecular links between cytoskeletal changes and MC
      function are incompletely understood. In this study, we provide genetic evidence
      for a critical role of the actin-regulatory proteins Coronin1a (Coro1a) and
      Coro1b on exocytic pathways in MCs: Coro1a(-/-) bone marrow-derived MCs exhibit
      increased FcepsilonRI-mediated degranulation of secretory lysosomes but
      significantly reduced secretion of cytokines. Hyperdegranulation of Coro1a(-/-)
      MCs is further augmented by the additional loss of Coro1b. In vivo, Coro1a(-/
      )Coro1b(-/-) mice displayed enhanced passive cutaneous anaphylaxis. Functional
      reconstitution assays revealed that the inhibitory effect of Coro1a on MC
      degranulation strictly correlates with cortical localization of Coro1a, requires
      its filamentous actin-binding activity, and is regulated by phosphorylation of
      Ser2 of Coro1a. Thus, coronin proteins, and in turn the actin cytoskeleton,
      exhibit a functional dichotomy as differential regulators of degranulation versus
      cytokine secretion in MC biology.

PMID- 21844204
TI  - Loss of Roquin induces early death and immune deregulation but not autoimmunity.
AB  - The substitution of one amino acid in the Roquin protein by the sanroque mutation
      induces a dramatic autoimmune syndrome in mice. This is believed to occur through
      ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained
      differentiation of follicular T helper cells, which induce spontaneous germinal
      center reactions to self-antigens. In this study, we demonstrate that tissue
      specific ablation of Roquin in T or B cells, in the entire hematopoietic system,
      or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of
      Roquin induced elevated expression of ICOS through T cell-intrinsic and 
      extrinsic mechanisms, which itself was not sufficient to break self-tolerance.
      Instead, ablation of Roquin in the hematopoietic system caused defined changes in
      immune homeostasis, including the expansion of macrophages, eosinophils, and T
      cell subsets, most dramatically CD8 effector-like T cells, through cell
      autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to
      perinatal lethality, which was partially rescued on the genetic background of an
      outbred strain. However, not even complete absence of Roquin resulted in overt
      self-reactivity, suggesting that the sanroque mutation induces autoimmunity
      through an as yet unknown mechanism.

PMID- 21844205
TI  - Anti-IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and
      protects against osteoporotic bone loss.
AB  - IL-20 is a proinflammatory cytokine of the IL-10 family that is involved in
      psoriasis, rheumatoid arthritis, atherosclerosis, and stroke. However, little is
      known about the role of IL-20 in bone destruction. We explored the function of IL
      20 in osteoclastogenesis and the therapeutic potential of anti-IL-20 monoclonal
      antibody 7E for treating osteoporosis. Higher serum IL-20 levels were detected in
      patients with osteopenia and osteoporosis and in ovariectomized (OVX) mice. IL-20
      mediates osteoclastogenesis by up-regulating the receptor activator of NF-kappaB
      (RANK) expression in osteoclast precursor cells and RANK ligand (RANKL) in
      osteoblasts. 7E treatment completely inhibited osteoclast differentiation induced
      by macrophage colony-stimulating factor (M-CSF) and RANKL in vitro and protected
      mice from OVX-induced bone loss in vivo. Furthermore, IL-20R1-deficient mice had
      significantly higher bone mineral density (BMD) than did wild-type controls. IL
      20R1 deficiency also abolished IL-20-induced osteoclastogenesis and increased BMD
      in OVX mice. We have identified a pivotal role of IL-20 in osteoclast
      differentiation, and we conclude that anti-IL-20 monoclonal antibody is a
      potential therapeutic for protecting against osteoporotic bone loss.

PMID- 21844206
TI  - The Paf oncogene is essential for hematopoietic stem cell function and
      development.
AB  - Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of
      all blood populations. Here, we show that the proliferating cell nuclear antigen
      associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays
      a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow
      cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia.
      These phenotypes are caused by a cell-intrinsic blockage in the development of
      long-term (LT)-HSCs into multipotent progenitors and preferential loss of
      lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In
      addition, LT-HSCs from Paf(-/-) mice had increased levels of reactive oxygen
      species (ROS), failed to maintain quiescence, and were unable to support LT
      hematopoiesis. The loss of lymphoid progenitors was likely due the increased
      levels of ROS in LT-HSCs caused by treatment of Paf(-/-) mice with the anti
      oxidant N-acetylcysteine restored lymphoid progenitor numbers to that of Paf(+/+)
      mice. Collectively, our studies identify Paf as a novel and essential regulator
      of early hematopoiesis.

PMID- 21844207
TI  - Actomyosin II contractility expels von Willebrand factor from Weibel-Palade
      bodies during exocytosis.
AB  - The study of actin in regulated exocytosis has a long history with many different
      results in numerous systems. A major limitation on identifying precise mechanisms
      has been the paucity of experimental systems in which actin function has been
      directly assessed alongside granule content release at distinct steps of
      exocytosis of a single secretory organelle with sufficient spatiotemporal
      resolution. Using dual-color confocal microscopy and correlative electron
      microscopy in human endothelial cells, we visually distinguished two sequential
      steps of secretagogue-stimulated exocytosis: fusion of individual secretory
      granules (Weibel-Palade bodies [WPBs]) and subsequent expulsion of von Willebrand
      factor (VWF) content. Based on our observations, we conclude that for fusion,
      WPBs are released from cellular sites of actin anchorage. However, once fused, a
      dynamic ring of actin filaments and myosin II forms around the granule, and
      actomyosin II contractility squeezes VWF content out into the extracellular
      environment. This study therefore demonstrates how discrete actin cytoskeleton
      functions within a single cellular system explain actin filament-based prevention
      and promotion of specific exocytic steps during regulated secretion.

PMID- 21844208
TI  - Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates
      epithelial reshaping.
AB  - The zonula adherens (ZA), a type of adherens junction (AJ), plays a major role in
      epithelial cell-cell adhesions. It remains unknown how the ZA is remodeled during
      epithelial reorganization. Here we found that the ZA was converted to another
      type of AJ with punctate morphology (pAJ) at the margins of epithelial colonies.
      The F-actin-stabilizing protein EPLIN (epithelial protein lost in neoplasm),
      which functions to maintain the ZA via its association with alphaE-catenin, was
      lost in the pAJs. Consistently, a fusion of alphaE-catenin and EPLIN contributed
      to the formation of ZA but not pAJs. We show that junctional tension was
      important for retaining EPLIN at AJs, and another force derived from actin fibers
      laterally attached to the pAJs inhibited EPLIN-AJ association. Vinculin was
      required for general AJ formation, and it cooperated with EPLIN to maintain the
      ZA. These findings suggest that epithelial cells remodel their junctional
      architecture by responding to mechanical forces, and the alphaE-catenin-bound
      EPLIN acts as a mechanosensitive regulator for this process.

PMID- 21844209
TI  - Lis1 is essential for cortical microtubule organization and desmosome stability
      in the epidermis.
AB  - Desmosomes are cell-cell adhesion structures that integrate cytoskeletal
      networks. In addition to binding intermediate filaments, the desmosomal protein
      desmoplakin (DP) regulates microtubule reorganization in the epidermis. In this
      paper, we identify a specific subset of centrosomal proteins that are recruited
      to the cell cortex by DP upon epidermal differentiation. These include Lis1 and
      Ndel1, which are centrosomal proteins that regulate microtubule organization and
      anchoring in other cell types. This recruitment was mediated by a region of DP
      specific to a single isoform, DPI. Furthermore, we demonstrate that the epidermal
      specific loss of Lis1 results in dramatic defects in microtubule reorganization.
      Lis1 ablation also causes desmosomal defects, characterized by decreased levels
      of desmosomal components, decreased attachment of keratin filaments, and
      increased turnover of desmosomal proteins at the cell cortex. This contributes to
      loss of epidermal barrier activity, resulting in completely penetrant perinatal
      lethality. This work reveals essential desmosome-associated components that
      control cortical microtubule organization and unexpected roles for centrosomal
      proteins in epidermal function.

PMID- 21844210
TI  - Aurora B dynamics at centromeres create a diffusion-based phosphorylation
      gradient.
AB  - Aurora B kinase is essential for successful cell division and regulates spindle
      assembly and kinetochore-microtubule interactions. The kinase localizes to the
      inner centromere until anaphase, but many of its substrates have distinct
      localizations, for example on chromosome arms and at kinetochores. Furthermore,
      substrate phosphorylation depends on distance from the kinase. How the kinase
      reaches substrates at a distance and how spatial phosphorylation patterns are
      determined are unknown. In this paper, we show that a phosphorylation gradient is
      produced by Aurora B concentration and activation at centromeres and release and
      diffusion to reach substrates at a distance. Kinase concentration, either at
      centromeres or at another chromosomal site, is necessary for activity globally.
      By experimentally manipulating dynamic exchange at centromeres, we demonstrate
      that the kinase reaches its substrates by diffusion. We also directly observe,
      using a fluorescence resonance energy transfer-based biosensor, phosphorylation
      spreading from centromeres after kinase activation. We propose that Aurora B
      dynamics and diffusion from the inner centromere create spatial information to
      regulate cell division.

PMID- 21844211
TI  - The DExD/H box ATPase Dhh1 functions in translational repression, mRNA decay, and
      processing body dynamics.
AB  - Translation, storage, and degradation of messenger ribonucleic acids (mRNAs) are
      key steps in the posttranscriptional control of gene expression, but how mRNAs
      transit between these processes remains poorly understood. In this paper, we
      functionally characterized the DExD/H box adenosine triphosphatase (ATPase) Dhh1,
      a critical regulator of the cytoplasmic fate of mRNAs. Using mRNA tethering
      experiments in yeast, we showed that Dhh1 was sufficient to move an mRNA from an
      active state to translational repression. In actively dividing cells,
      translational repression was followed by mRNA decay; however, deleting components
      of the 5'-3' decay pathway uncoupled these processes. Whereas Dhh1's ATPase
      activity was not required to induce translational inhibition and mRNA decay when
      directly tethered to an mRNA, ATP hydrolysis regulated processing body dynamics
      and the release of Dhh1 from these RNA-protein granules. Our results place Dhh1
      at the interface of translation and decay controlling whether an mRNA is
      translated, stored, or decayed.

PMID- 21844212
TI  - ABT-898 induces tumor regression and prolongs survival in a mouse model of
      epithelial ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and is
      often not diagnosed until late stages due to its asymptomatic nature. Women
      diagnosed with EOC typically undergo surgical debulking followed by chemotherapy;
      however, disease recurrence often occurs. In this study, we evaluated the ability
      of the thrombospondin-1 mimetic peptide, ABT-898, to regress established, late
      stage tumors in a mouse model of human EOC. Ovarian tumors were induced and ABT
      898 treatment was initiated at time points that were representative of late
      stages of the disease to study tumor regression. ABT-898 induced tumor regression
      and reduced the morbidity of treated animals compared with controls. Analysis of
      tumors from ABT-898-treated animals showed reduced abnormal tumor vasculature,
      decreased expression of the proangiogenic compound VEGF, and reduced tumor tissue
      hypoxia. ABT-898 treatment initiated at late-stage disease also significantly
      prolonged disease-free survival compared with control animals. Results from this
      study show that ABT-898 is capable of regressing established ovarian tumors in an
      animal model of the disease. As most women are detected at advanced stage EOC,
      ABT-898 may improve our treatment of ovarian cancer.

PMID- 21844213
TI  - Factors affecting warfarin-related knowledge and INR control of patients
      attending physician- and pharmacist-managed anticoagulation clinics.
AB  - OBJECTIVES: To assess the anticoagulation knowledge and international normalized
      ratio (INR) control among patients on warfarin. METHODS: A cross-sectional study
      with 156 randomly sampled patients from physician- (non-medication therapy
      adherence clinic [non-MTAC]) and pharmacist (MTAC)-run anticoagulation clinics
      using a validated interviewer-administered questionnaire. Patients' INR readings
      from 2008 to 2010 were recorded. RESULTS: Patients on warfarin scored an average
      of 66.5% +/- 36.0% for their knowledge on how warfarin works, 42.9% +/- 44.9% for
      interaction between warfarin and alcohol, and 49.2% +/- 21.1% for adverse
      effects. No significant differences were found between MTAC and non-MTAC patients
      on their knowledge. There was a negative correlation between patients' knowledge
      and age (P = .001, r (s) = -.293) and a positive correlation between patients'
      knowledge and education level (P = .001, r (s) = .365). MTAC patients were found
      to have better INR control than non-MTAC when compared for mean percentage days
      in range (63.4% +/- 18.9% vs 52.5% +/- 18.2%; P = .006) and mean percentage
      visits in range (58.8% +/- 17.9% vs 46.8% +/- 18.6%; P = .001). CONCLUSIONS: MTAC
      patients were found to have better INR control compared to non-MTAC patients. A
      joint cooperation between physicians, pharmacists, and nurses should exist to
      achieve desired therapeutic outcomes.

PMID- 21844214
TI  - The pharmacists' role in improving guideline compliance for thyroid function
      testing in patients with heart failure.
AB  - This single-center retrospective pilot program's objective was to utilize
      outpatient pharmacists to improve laboratory test adherence in chronic heart
      failure (CHF) patients overdue for thyroid function testing, thereby
      demonstrating the value of the outpatient pharmacist and justifying possible
      clinical role expansion. Thyroid disorders may contribute to CHF development,
      progression, and exacerbation. Testing is the standard of care in CHF patients
      per American Heart Association's 2009 Guidelines. Delinquency was defined as labs
      not conducted within 1 year in patients with euthyroid history, within 6 months
      in patients with thyroid dysfunction, abnormal labs at any time without follow
      up, or lab absence after thyroid medication initiation, adjustment, or
      discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent
      thyroid function tests were counseled to get thyroid labs at point of sale, via
      telephone, e-mail, or letter. In collaboration with physicians, pharmacists
      ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients
      with abnormal laboratory results, pharmacists coordinated drug therapy and follow
      up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two
      patients (90%) previously delinquent for thyroid function testing received
      relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests
      not on prior drug therapy received treatment.

PMID- 21844215
TI  - Developing a communication skills training program for pharmacists working in
      Southern African HIV/AIDS contexts: some notes on process and challenges.
AB  - In an attempt to understand why patients do not take medications, researchers are
      increasingly focusing on how communication processes influence adherence
      behaviors. Pharmacists have an important role to play in this regard. However,
      existing communication skills training (CST) programs for pharmacists are not
      necessarily sensitive to the needs of pharmacists working in specific contexts
      such as Southern Africa. In addition, CST programs are often poorly described in
      the literature, lack a theoretical background, and focus excessively on
      evaluation. This article describes the process of developing a CST program for
      pharmacists working in Southern African HIV/AIDS contexts, focusing on
      conceptualization and design. Some shortfalls in current approaches to CST are
      addressed. A number of sources were consulted during the development phase of the
      project, including interactional and focus group research, previously developed
      training models, analysis of currently available CST materials for pharmacists,
      and a literature review. These are discussed and some attention is also given to
      the challenges of implementing and evaluating the program. The project highlights
      the importance of providing CST that is disease- and context-specific, grounded
      in appropriate research and theoretical frameworks, and based on a rigorous
      process of development.

PMID- 21844216
TI  - Probable quetiapine-mediated prolongation of the QT interval.
AB  - PURPOSE: QT prolongation can occur with both first- (FGA) and second-generation
      antipsychotics (SGA). QT prolongation was identified in an adult patient who
      presented to the emergency room with schizophrenia, fluid and electrolyte
      imbalances, and pneumonia. Quetiapine, an SGA, was a component of the
      pharmacotherapy regimen. Based on the Naranjo adverse drug reaction probability
      scale rating criteria, a probable causal association was made. METHODS: PubMed
      and Ovid were searched using the terms antipsychotic, psychotropic, QT interval,
      corrected QT interval (QTc) prolongation, and quetiapine. References were
      examined for additional articles related to antipsychotic drugs and the QT
      interval. DISCUSSION: In this patient, the use of quetiapine was identified as a
      contributing factor in QT prolongation. Prior QT prolongation was experienced
      with ziprasidone, another SGA. The antidepressant and dose remained consistent
      throughout the inpatient course of treatment. Other risk factors in this patient
      included hypokalemia, dehydration, pneumonia, age, gender, and concurrent usage
      of an antidepressant. Dual psychiatric diagnoses, preexisting cardiovascular
      disease, and electrolyte disturbances may increase this risk potential.
      CONCLUSION: Psychiatric patients may be more at risk of cardiovascular
      complications, such as QT interval prolongation. The pharmacist can help evaluate
      risk factors and provide input into the care of all patients, particularly those
      identified as at risk.

PMID- 21844217
TI  - Development of a comprehensive community pharmacy patient intake form compliant
      with OBRA'90 requirements.
AB  - OBJECTIVE: To identify whether community pharmacies are collecting the minimum
      patient information mandated by the Omnibus Budget Reconciliation Act of 1990
      (OBRA'90), and to create an intake form that meets and exceeds these
      requirements. METHODS: Chain, mass merchandiser, supermarket, and wholesale
      pharmacies located within the state of Florida were eligible for selection. Only
      1 pharmacy was selected from each company. The research assistant asked the
      pharmacy employee to describe all information requested from a patient who is
      bringing in a prescription for the first time and/ or provide a blank copy of
      their existing patient intake form. Patient intake information forms were
      collected between July 2008 and February 2009. RESULTS: Of the 10 pharmacies
      included in this study (3 supermarkets, 3 mass merchandisers, 2 wholesale
      pharmacies, and 2 chain pharmacies), 40% of the studied pharmacies collected
      information on patient medications. All pharmacies collected at least 6
      information requirements. Only 1 pharmacy was compliant with OBRA'90 requirements
      evaluated. CONCLUSION: By obtaining this information providers are in a better
      position to assist with avoiding medication errors and to help with the medical
      reconciliation process in health systems.

PMID- 21844218
TI  - Asian student depression in American high schools: differences in risk factors.
AB  - There are inconsistent findings about depression in Asians. This study examined
      risk factors for depression in Asian and Caucasian adolescents. Stratified
      bivariate secondary analyses of risk indicators and depressed mood were performed
      in this cross-sectional study of high school survey data (9th to 12th grades)
      from 2,542 students (198 Asian). Asians had a higher prevalence of depressed
      symptoms, but similar risk factors as Caucasians. Smoking and injury at work were
      major risk factors for depressed mood among Asians. Asian-specific risk factors
      for depression were being foreign-born and having a work-related injury. Asian
      and Caucasian teens have similar risk factors for depressed mood, though being
      foreign born and having a work-related injury are risk factors specific to Asian
      youth, possibly related to social-economic status. Providers of care in school,
      such as school nurses, can be important primary screeners of depression for Asian
      students in particular.

PMID- 21844219
TI  - Coexpression and activation of TRPV1 suppress the activity of the KCNQ2/3
      channel.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective
      cation channel expressed predominantly in peripheral nociceptors. By detecting
      and integrating diverse noxious thermal and chemical stimuli, and as a result of
      its sensitization by inflammatory mediators, the TRPV1 receptor plays a key role
      in inflammation-induced pain. Activation of TRPV1 leads to a cascade of pro
      nociceptive mechanisms, many of which still remain to be identified. Here, we
      report a novel effect of TRPV1 on the activity of the potassium channel KCNQ2/3,
      a negative regulator of neuronal excitability. Using ion influx assays, we
      revealed that TRPV1 activation can abolish KCNQ2/3 activity, but not vice versa,
      in human embryonic kidney (HEK)293 cells. Electrophysiological studies showed
      that coexpression of TRPV1 caused a 7.5-mV depolarizing shift in the voltage
      dependence of KCNQ2/3 activation compared with control expressing KCNQ2/3 alone.
      Furthermore, activation of TRPV1 by capsaicin led to a 54% reduction of KCNQ2/3
      mediated current amplitude and attenuation of KCNQ2/3 activation. The inhibitory
      effect of TRPV1 appears to depend on Ca(2+) influx through the activated channel
      followed by Ca(2+)-sensitive depletion of phosphatidylinositol 4,5-bisphosphate
      and activation of protein phosphatase calcineurin. We also identified physical
      interactions between TRPV1 and KCNQ2/3 coexpressed in HEK293 cells and in rat
      dorsal root ganglia neurons. Mutation studies established that this interaction
      is mediated predominantly by the membrane-spanning regions of the respective
      proteins and correlates with the shift of KCNQ2/3 activation. Collectively, these
      data reveal that TRPV1 activation may deprive neurons from inhibitory control
      mediated by KCNQ2/3. Such neurons may thus have a lower threshold for activation,
      which may indirectly facilitate TRPV1 in integrating multiple noxious signals
      and/or in the establishment or maintenance of chronic pain.

PMID- 21844220
TI  - Mechanism for modulation of gating of connexin26-containing channels by taurine.
AB  - The mechanisms of action of endogenous modulatory ligands of connexin channels
      are largely unknown. Previous work showed that protonated aminosulfonates (AS),
      notably taurine, directly and reversibly inhibit homomeric and heteromeric
      channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32
      channels. The present study investigated the molecular mechanisms of connexin
      channel modulation by taurine, using hemichannels and junctional channels
      composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28
      amino acid "tag" to the carboxyl-terminal domain (CT) of Cx26 (Cx26(T))
      eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells
      and liposomes. Cleavage of all but four residues of the tag (Cx26(Tc)) resulted
      in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine
      inhibition of heteromeric hemichannels (Cx26(Tc)/Cx32). Taurine actions on
      junctional channels were fully consistent with those on hemichannels. Taurine
      induced inhibition of Cx26/Cx32(T) and nontagged Cx26 junctional channels was
      blocked by extracellular HEPES, a blocker of the taurine transporter, confirming
      that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic
      resonance of peptides corresponding to Cx26 cytoplasmic domains showed that
      taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL
      directly interact. ELISA showed that taurine disrupts a pH-dependent interaction
      between the CT and the CT-proximal half of the CL. These studies reveal that AS
      disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing
      channels, causing closure, and that the Cx26CT has a modulatory role in Cx26
      function.

PMID- 21844221
TI  - An acetylcholine receptor lacking both gamma and epsilon subunits mediates
      transmission in zebrafish slow muscle synapses.
AB  - Fast and slow skeletal muscle types in larval zebrafish can be distinguished by a
      fivefold difference in the time course of their synaptic decay. Single-channel
      recordings indicate that this difference is conferred through kinetically
      distinct nicotinic acetylcholine receptor (AChR) isoforms. The underlying basis
      for this distinction was explored by cloning zebrafish muscle AChR subunit cDNAs
      and expressing them in Xenopus laevis oocytes. Measurements of single-channel
      conductance and mean open burst duration assigned alpha(2)betadeltaepsilon to
      fast muscle synaptic current. Contrary to expectations, receptors composed of
      only alphabetadelta subunits (presumed to be alpha(2)betadelta(2) receptors)
      recapitulated the kinetics and conductance of slow muscle single-channel
      currents. Additional evidence in support of gamma/epsilon-less receptors as
      mediators of slow muscle synapses was reflected in the inward current
      rectification of heterologously expressed alpha(2)betadelta(2) receptors, a
      property normally associated with neuronal-type nicotinic receptors. Similar
      rectification was reflected in both single-channel and synaptic currents in slow
      muscle, distinguishing them from fast muscle. The final evidence for
      alpha(2)betadelta(2) receptors in slow muscle was provided by our ability to
      convert fast muscle synaptic currents to those of slow muscle by knocking down
      epsilon subunit expression in vivo. Thus, for the first time, muscle synaptic
      function can be ascribed to a receptor isoform that is composed of only three
      different subunits. The unique functional features offered by the
      alpha(2)betadelta(2) receptor likely play a central role in mediating the
      persistent contractions characteristic to this muscle type.

PMID- 21844223
TI  - Regulating the shuttling of eukaryotic RNA polymerase II.

PMID- 21844222
TI  - Reducing plasma membrane sphingomyelin increases insulin sensitivity.
AB  - It has been shown that inhibition of de novo sphingolipid synthesis increases
      insulin sensitivity. For further exploration of the mechanism involved, we
      utilized two models: heterozygous serine palmitoyltransferase (SPT) subunit 2
      (Sptlc2) gene knockout mice and sphingomyelin synthase 2 (Sms2) gene knockout
      mice. SPT is the key enzyme in sphingolipid biosynthesis, and Sptlc2 is one of
      its subunits. Homozygous Sptlc2-deficient mice are embryonic lethal. However,
      heterozygous Sptlc2-deficient mice that were viable and without major
      developmental defects demonstrated decreased ceramide and sphingomyelin levels in
      the cell plasma membranes, as well as heightened sensitivity to insulin.
      Moreover, these mutant mice were protected from high-fat diet-induced obesity and
      insulin resistance. SMS is the last enzyme for sphingomyelin biosynthesis, and
      SMS2 is one of its isoforms. Sms2 deficiency increased cell membrane ceramide but
      decreased SM levels. Sms2 deficiency also increased insulin sensitivity and
      ameliorated high-fat diet-induced obesity. We have concluded that Sptlc2
      heterozygous deficiency- or Sms2 deficiency-mediated reduction of SM in the
      plasma membranes leads to an improvement in tissue and whole-body insulin
      sensitivity.

PMID- 21844225
TI  - Roles of RSC, Rad59, and cohesin in double-strand break repair.

PMID- 21844224
TI  - Spt6 is required for heterochromatic silencing in the fission yeast
      Schizosaccharomyces pombe.
AB  - Spt6 is a conserved factor, critically required for several transcription- and
      chromatin-related processes. We now show that Spt6 and its binding partner, Iws1,
      are required for heterochromatic silencing in Schizosaccharomyces pombe. Our
      studies demonstrate that Spt6 is required for silencing of all heterochromatic
      loci and that an spt6 mutant has an unusual combination of heterochromatic
      phenotypes compared to previously studied silencing mutants. Unexpectedly, we
      find normal nucleosome positioning over heterochromatin and normal levels of
      histone H3K9 dimethylation at the endogenous pericentric repeats. However, we
      also find greatly reduced levels of H3K9 trimethylation, elevated levels of H3K14
      acetylation, reduced recruitment of several silencing factors, and defects in
      heterochromatin spreading. Our evidence suggests that Spt6 plays a role at both
      the transcriptional and posttranscriptional levels; in an spt6 mutant, RNA
      polymerase II (RNAPII) occupancy at the pericentric regions is only modestly
      increased, while production of small interfering RNAs (siRNAs) is lost. Taken
      together, our results suggest that Spt6 is required for multiple steps in
      heterochromatic silencing by controlling chromatin, transcriptional, and
      posttranscriptional processes.

PMID- 21844226
TI  - Deregulation of the p57-E2F1-p53 axis results in nonobstructive hydrocephalus and
      cerebellar malformation in mice.
AB  - The cyclin-dependent kinase inhibitor (CKI) p57(Kip2) plays a pivotal role in
      cell cycle arrest during development, in particular, in the regulation of the
      entry of proliferating progenitors into quiescence. The gene encoding p57
      undergoes genomic imprinting, and impairment of the regulation of p57 expression
      results in various developmental anomalies in humans and mice. We now show that
      p57 is expressed predominantly in the subcommissural organ and cerebellar
      interneurons in the mouse brain and that mice with brain-specific deletion of the
      p57 gene (Kip2) manifest prominent nonobstructive hydrocephalus as well as
      cerebellar malformation associated with the loss of Pax2-positive interneuron
      precursors and their descendants, including Golgi cells and gamma-aminobutyric
      acid-containing neurons of the deep cerebellar nuclei. These abnormalities were
      found to be attributable to massive apoptosis of precursor cells in the
      developing brain. The morphological defects of the p57-deficient mice were
      corrected by knock-in of the gene for the related CKI p27(Kip1) at the Kip2
      locus. The abnormalities were also prevented by additional genetic ablation of
      p53 or E2F1. Our results thus implicate p57 in cell cycle arrest in the
      subcommissural organ and Pax2-positive interneuron precursors, with the lack of
      p57 resulting in induction of p53-dependent apoptosis due to hyperactivation of
      E2F1.

PMID- 21844227
TI  - QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates
      cancer cell proliferation.
AB  - The histone variant macroH2A1 contains a carboxyl-terminal ~30-kDa domain called
      a macro domain. MacroH2A1 is produced as one of two alternatively spliced forms,
      macroH2A1.1 and macroH2A1.2. While the macro domain of macroH2A1.1 can interact
      with NAD(+)-derived small molecules, such as poly(ADP-ribose), macroH2A1.2's
      macro domain cannot. Here, we show that changes in the alternative splicing of
      macroH2A1 pre-mRNA, which lead to a decrease in macroH2A1.1 expression, occur in
      a variety of cancers, including testicular, lung, bladder, cervical, breast,
      colon, ovarian, and endometrial. Furthermore, reintroduction of macroH2A1.1
      suppresses the proliferation of lung and cervical cancer cells in a manner that
      requires the ability of macroH2A1.1 to bind NAD(+)-derived metabolites.
      MacroH2A1.1-mediated suppression of proliferation occurs, at least in part,
      through the reduction of poly(ADP-ribose) polymerase 1 (PARP-1) protein levels.
      By analyzing publically available expression and splicing microarray data, we
      identified splicing factors that correlate with alterations in macroH2A1
      splicing. Using RNA interference, we demonstrate that one of these factors, QKI,
      regulates the alternative splicing of macroH2A1 pre-mRNA, resulting in increased
      levels of macroH2A1.1. Finally, we demonstrate that QKI expression is
      significantly reduced in many of the same cancer types that demonstrate a
      reduction in macroH2A1.1 splicing.

PMID- 21844228
TI  - Type III secretion system-dependent translocation of ectopically expressed Yop
      effectors into macrophages by intracellular Yersinia pseudotuberculosis.
AB  - Yersinia pseudotuberculosis is a Gram-negative bacterial pathogen. Virulence in
      Y. pseudotuberculosis requires the plasmid-encoded Ysc type III secretion system
      (T3SS), which functions to translocate a set of effectors called Yops into
      infected host cells. The effectors function to antagonize phagocytosis (e.g.,
      YopH) or to induce apoptosis (YopJ) in macrophages infected with Y.
      pseudotuberculosis. Additionally, when antiphagocytosis is incomplete and Y.
      pseudotuberculosis is internalized by macrophages, the bacterium can survive in
      phagosomes. Previous studies have shown that delivery of effectors into host
      cells occurs efficiently when Yersinia is extracellular. However, it is not clear
      whether the T3SS can be utilized by intracellular Y. pseudotuberculosis to
      translocate Yops. This possibility was investigated here using Y.
      pseudotuberculosis strains that express YopJ or YopH under the control of an
      inducible promoter. Bone marrow-derived murine macrophages were infected with
      these strains under conditions that prevented the survival of extracellular
      bacteria. Effector translocation was detected by measuring apoptosis or the
      activities of Yop-beta-lactamase fusion proteins. Results showed that macrophages
      underwent apoptosis when YopJ expression was induced prior to phagocytosis,
      confirming that delivery of this effector prior to or during uptake is sufficient
      to cause cell death. However, macrophages also underwent apoptosis when YopJ was
      ectopically expressed after phagocytosis; furthermore, expression of the
      translocator YopB from intracellular bacteria also resulted in increased cell
      death. Analysis by microscopy showed that translocation of ectopically expressed
      YopH- or YopJ-beta-lactamase fusions could be correlated with the presence of
      viable Y. pseudotuberculosis in macrophages. Collectively, our results suggest
      that the Ysc T3SS of Y. pseudotuberculosis can function within macrophage
      phagosomes to translocate Yops into the host cytosol.

PMID- 21844229
TI  - The novel leptospiral surface adhesin Lsa20 binds laminin and human plasminogen
      and is probably expressed during infection.
AB  - Leptospirosis is an emerging infectious disease caused by pathogenic species of
      Leptospira. In this work, we report the cloning, expression, purification, and
      characterization of two predicted leptospiral outer membrane proteins, LIC11469
      and LIC11030. The LIC11469 protein is well conserved among leptospiral strains,
      while LIC11030 was identified only in Leptospira interrogans. We confirmed by
      surface proteolysis of intact leptospires with proteinase K that these proteins
      are most likely new surface leptospiral proteins. The recombinant proteins were
      evaluated for their capacity to attach to extracellular matrix (ECM) components
      and to plasminogen. The leptospiral protein encoded by LIC11469, named Lsa20
      (leptospiral surface adhesin of 20 kDa), binds to laminin and to plasminogen. The
      binding with both components was not detected when Lsa20 was previously denatured
      or blocked with anti-Lsa20 antibodies. Moreover, Lsa20 binding to laminin was
      also confirmed by surface plasmon resonance (SPR). Laminin competes with
      plasminogen for binding to Lsa20, suggesting the same ligand-binding site. Lsa20
      bound plasminogen could be converted to enzymatically active plasmin, capable of
      cleaving plasmin substrate d-valyl-leucyl-lysine-p-nitroanilide dihydrochloride.
      Lsa20 was recognized by antibodies in confirmed-leptospirosis serum samples,
      suggesting that this protein is expressed during infection. Taken together, our
      results indicate that Lsa20 is a novel leptospiral adhesin that in concert with
      the host-derived plasmin may help the bacteria to adhere and to spread through
      the hosts.

PMID- 21844231
TI  - A naturally occurring single-residue mutation in the translocator domain of
      Neisseria meningitidis NhhA affects trimerization, surface localization, and
      adhesive capabilities.
AB  - Neisseria meningitidis NhhA (Neisseria hia/hsf homologue A) is an oligomeric
      outer membrane protein belonging to the family of trimeric autotransporter
      adhesins. NhhA mediates the interaction of N. meningitidis with human epithelial
      cells and components of the extracellular matrix. The recombinant protein is able
      to induce bactericidal antibodies and hence has also been considered a potential
      vaccine candidate. In this study, we analyzed the production of NhhA in a large
      panel of N. meningitidis strains belonging to different serogroups and clonal
      complexes. We found that trimeric NhhA was produced at different levels by the
      various strains tested. In some strains belonging to the clonal complex ST41/44,
      the protein is detectable only as a monomer. Sequencing of the nhhA gene and
      generation of complementing strains in different genetic backgrounds have proved
      that a single mutation (Gly to Asp) in the translocator domain affected both
      trimerization and surface localization of NhhA. In vitro infection assays showed
      that this mutation impairs meningococcal NhhA-mediated adhesion, suggesting that
      strains carrying the mutation may rely on different strategies or molecules to
      mediate interaction with host cells. Finally, we demonstrated that N.
      meningitidis ST41/44 strains producing the mutated form did not induce killing
      mediated by NhhA-specific bactericidal antibodies. Our data help to elucidate the
      secretion mechanisms of trimeric autotransporters and to understand the
      contribution of NhhA in the evolutionary process of host-Neisseria interactions.
      Also, they might have important implications for the evaluation of NhhA as a
      vaccine candidate.

PMID- 21844230
TI  - Receptor-interacting protein 2 controls pulmonary host defense to Escherichia
      coli infection via the regulation of interleukin-17A.
AB  - Recognition of microbial patterns by host receptors is the first step in a
      multistep sequence leading to neutrophil-dependent host resistance. Although the
      role of membrane-bound sensors in bacterial recognition has been examined in
      detail, the importance of cytosolic sensors in the lungs is largely unexplored.
      In this context, there is a major lack of understanding related to the downstream
      signaling mediators, such as cells and/or molecules, during acute extracellular
      Gram-negative bacterial pneumonia. In order to determine the role of NOD-like
      receptors (NLRs), we used an experimental Escherichia coli infection model using
      mice deficient in the gene coding for the NLR adaptor, receptor-interacting
      protein 2 (RIP2). RIP2(-/-) mice with E. coli infection displayed higher
      bacterial burden and reduced neutrophil recruitment and tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), macrophage inflammatory protein 2 (MIP
      2), and CXCL5/LIX expression, along with attenuated histopathological changes in
      the lungs. Decreased IL-17A levels were observed, along with lower numbers of IL
      17A-producing T cells, in RIP2(-/-) mice after infection. RIP2(-/-) mice also
      show reduced IL-6 and IL-23 levels in the lungs, along with decreased activation
      of STAT3 after infection. Furthermore, activation of NF-kappaB and mitogen
      activated protein kinases (MAPKs) and expression of intercellular adhesion
      molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in the lungs
      of infected RIP2(-/-) mice were attenuated following infection. Although
      neutrophil mobilization to the blood was impaired in RIP2(-/-) mice following
      infection, the expression of CD62P, CD11a/18, CD11b, and CXCR2 on blood and lung
      neutrophils was not altered between infected wild-type (WT) and RIP2(-/-) mice.
      Thus, RIP2 contributes to neutrophil-dependent host defense against an
      extracellular Gram-negative pathogen via (i) IL-17A regulation and (ii)
      neutrophil mobilization to the blood.

PMID- 21844232
TI  - Gene expression profiles of immune mediators and histopathological findings in
      animal models of leptospirosis: comparison between susceptible hamsters and
      resistant mice.
AB  - Leptospirosis is a widespread zoonosis characterized by multiple organ failure
      and variable host susceptibility toward pathogenic Leptospira strains. In this
      study, we put the role of inflammatory mediators in parallel with bacterial
      burdens and organ lesions by comparing a susceptible animal model, the hamster,
      and a resistant one, the Oncins France 1 (OF1) mouse, both infected with virulent
      Leptospira interrogans serovar Icterohaemorrhagiae strain Verdun. Histological
      observations evidenced edema, congestion, hemorrhage, and inflammatory
      infiltration in the organs of hamsters, in contrast to limited changes in mice.
      Using reverse transcription-quantitative PCR techniques, we showed that the
      relative Leptospira burden progressively increased in hamster tissues, while a
      rapid clearance was observed in mouse tissues. The early regulation of the
      proinflammatory mediators interleukin-1beta (IL-1beta), IL-6, tumor necrosis
      factor alpha, and cyclo-oxygenase-2 and the chemokines gamma interferon-inducible
      protein 10 kDa/CXCL10 and macrophage inflammatory protein-1alpha/CCL3 in mouse
      tissues contrasted with their delayed and massive overexpression in hamster
      tissues. Conversely, the induction of the anti-inflammatory cytokine IL-10 was
      faster in the resistant than in the susceptible animal model. The role of these
      cytokines in the pathophysiology of leptospirosis and the implications of their
      differential regulation in the development of this disease are discussed.

PMID- 21844233
TI  - Impact of toll-like receptor 2 deficiency on immune responses to mycobacterial
      antigens.
AB  - In the present study, we addressed the question of whether Toll-like receptor 2
      (TLR2)-mediated innate immunity can contribute to the development of acquired
      immune responses. We immunized TLR2(-/-) and wild-type (WT) mice three times
      subcutaneously with the mycobacterial antigen (Ag19kDa) (a TLR2 ligand) or Ag85A
      (not a TLR2 ligand). One week after the last immunization, sera and spleens were
      collected. To evaluate cellular responses, we measured gamma interferon (IFN
      gamma) after in vitro restimulation of spleen cells with antigen alone or antigen
      pulsed bone marrow-derived macrophages (BMM(Ag)) or pulmonary macrophages
      (PuM(Ag)). Antibody responses were comparable in the two mouse strains, but we
      observed differences in the cellular responses. Recall responses to Ag85A were
      similar in the two strains, but responses to Ag19kDa given alone or presented by
      BMM or PuM were lower in TLR2(-/-) than in WT mice. The largest differences in
      cellular responses were observed when Ag19kDa was presented by PuM. To understand
      this, we analyzed phenotypic and functional differences between BMM and PuM upon
      stimulation with various ligands. Generally, PuM had a lower response to the TLR2
      ligand Pam(3)Cys-Ser-(Lys)(4) trihydrochloride and to anti-CD40 than BMM, as
      measured by cytokine secretion and upregulation of costimulatory molecules. This
      might provide a partial explanation for the lower capacity of PuM when pulsed
      with Ag19kDa, also a TLR2 ligand. Altogether, our results revealed weaknesses in
      the T cell and antigen-presenting cell (APC) compartments of the Ag19kDa
      immunized TLR2(-/-) mice but indicated that specific immune responses could be
      generated in the absence of TLR2 regardless of the characteristics of the antigen
      used.

PMID- 21844234
TI  - Interleukin-1 receptor-associated kinase 4 is essential for initial host control
      of Brucella abortus infection.
AB  - Brucella abortus is a facultative intracellular bacterial pathogen that causes
      abortion in domestic animals and undulant fever in humans. Recent studies have
      revealed that Toll-like receptor (TLR)-initiated immune response to Brucella spp.
      depends on myeloid differentiation factor 88 (MyD88) signaling. Therefore, we
      decided to study the role of the interleukin-1 receptor-associated kinase 4 (IRAK
      4) in host innate immune response against B. abortus. After Brucella infection,
      it was shown that the number of CFU in IRAK-4(-/-) mice was high compared to that
      in IRAK-4(+/-) animals only at 1 week postinfection. At 3 and 6 weeks
      postinfection, IRAK-4(-/-) mice were able to control the infection similarly to
      heterozygous animals. Furthermore, the type 1 cytokine profile was evaluated.
      IRAK-4(-/-) mice showed lower production of systemic interleukin-12 (IL-12) and
      gamma interferon (IFN-gamma). Additionally, a reduced percentage of CD4(+) and
      CD8(+) T cells expressing IFN-gamma was observed compared to IRAK-4(+/-).
      Further, the production of IL-12 and tumor necrosis factor alpha (TNF-alpha) by
      macrophages and dendritic cells from IRAK-4(-/-) mice was abolished at 24 h after
      stimulation with B. abortus. To investigate the role of IRAK-4 in mitogen
      activated protein kinase (MAPK) and NF-kappaB signaling pathways, macrophages
      were stimulated with B. abortus, and the signaling components were analyzed by
      protein phosphorylation. Extracellular signal-regulated kinase 1 (ERK1) and ERK2
      and p38 as well as p65 NF-kappaB phosphorylation was profoundly impaired in IRAK
      4(-/-) and MyD88(-/-) macrophages activated by Brucella. In summary, the results
      shown in this study demonstrated that IRAK-4 is critical to trigger the initial
      immune response against B. abortus but not at later phases of infection.

PMID- 21844235
TI  - Structural and functional interactions between the cholera toxin A1 subunit and
      ERdj3/HEDJ, a chaperone of the endoplasmic reticulum.
AB  - Cholera toxin (CT) is endocytosed and transported by vesicle carriers to the
      endoplasmic reticulum (ER). The catalytic CTA1 subunit then crosses the ER
      membrane and enters the cytosol, where it interacts with its Gsalpha target. The
      CTA1 membrane transversal involves the ER chaperone BiP, but few other host
      proteins involved with CTA1 translocation are known. BiP function is regulated by
      ERdj3, an ER-localized Hsp40 chaperone also known as HEDJ. ERdj3 can also
      influence protein folding and translocation by direct substrate binding. In this
      work, structural and functional assays were used to examine the putative
      interaction between ERdj3 and CTA1. Cell-based assays demonstrated that
      expression of a dominant negative ERdj3 blocks CTA1 translocation into the
      cytosol and CT intoxication. Binding assays with surface plasmon resonance
      demonstrated that monomeric ERdj3 interacts directly with CTA1. This interaction
      involved the A1(2) subdomain of CTA1 and was further dependent upon the overall
      structure of CTA1: ERdj3 bound to unfolded but not folded conformations of the
      isolated CTA1 subunit. This was consistent with the chaperone function of ERdj3,
      as was the ability of ERdj3 to mask the solvent-exposed hydrophobic residues of
      CTA1. Our data identify ERdj3 as a host protein involved with the CT intoxication
      process and provide new molecular details regarding CTA1-chaperone interactions.

PMID- 21844236
TI  - Infection intensity-dependent responses of Anopheles gambiae to the African
      malaria parasite Plasmodium falciparum.
AB  - Malaria remains a devastating disease despite efforts at control and prevention.
      Extensive studies using mostly rodent infection models reveal that successful
      Plasmodium parasite transmission by the African mosquito vector Anopheles gambiae
      depends on finely tuned vector-parasite interactions. Here we investigate the
      transcriptional response of A. gambiae to geographically related Plasmodium
      falciparum populations at various infection intensities and different infection
      stages. These responses are compared with those of mosquitoes infected with the
      rodent parasite Plasmodium berghei. We demonstrate that mosquito responses are
      largely dependent on the intensity of infection. A major transcriptional
      suppression of genes involved in the regulation of midgut homeostasis is detected
      in low-intensity P. falciparum infections, the most common type of infection in
      Africa. Importantly, genes transcriptionally induced during these infections tend
      to be phylogenetically unique to A. gambiae. These data suggest that coadaptation
      between vectors and parasites may act to minimize the impact of infection on
      mosquito fitness by selectively suppressing specific functional classes of genes.
      RNA interference (RNAi)-mediated gene silencing provides initial evidence for
      important roles of the mosquito G protein-coupled receptors (GPCRs) in
      controlling infection intensity-dependent antiparasitic responses.

PMID- 21844237
TI  - Coordinate control of the locus of enterocyte effacement and enterohemolysin
      genes by multiple common virulence regulators in enterohemorrhagic Escherichia
      coli.
AB  - The locus of enterocyte effacement (LEE) pathogenicity island is required for the
      intimate adhesion of enterohemorrhagic Escherichia coli (EHEC) to the intestinal
      epithelial cells. GrlR and GrlA are LEE-encoded negative and positive regulators,
      respectively. The interaction of these two regulators is important for
      controlling the transcription of LEE genes through Ler, a LEE-encoded central
      activator for the LEE. The GrlR-GrlA regulatory system controls not only LEE but
      also the expression of the flagellar and enterohemolysin (Ehx) genes in EHEC.
      Since Ehx levels were markedly induced in a grlR mutant but not in a grlR grlA
      double mutant and significantly increased by overexpression of GrlA in a ler
      mutant, GrlA is responsible for this regulation (T. Saitoh et al., J. Bacteriol.
      190:4822-4830, 2008). In this study, additional investigations of the regulation
      of ehx gene expression determined that Ler also acts as an activator for Ehx
      expression without requiring GrlA function. We recently reported that the LysR
      type regulator LrhA positively controls LEE expression (N. Honda et al., Mol.
      Microbiol. 74:1393-1411, 2009). The hemolytic activity of the lrhA mutant strain
      of EHEC was lower than that of the wild-type strain, and LrhA markedly induced
      ehx transcription in an E. coli K-12 strain, suggesting that LrhA also activates
      the transcription of ehx without GrlA and Ler. Gel mobility shift assays
      demonstrated that Ler and LrhA directly bind to the regulatory region of ehxC.
      Together, these results indicate that transcription of ehx is positively
      regulated by Ler, GrlA, and LrhA, which all act as positive regulators for LEE
      expression.

PMID- 21844238
TI  - Proteomic analysis of Anaplasma phagocytophilum during infection of human myeloid
      cells identifies a protein that is pronouncedly upregulated on the infectious
      dense-cored cell.
AB  - Anaplasma phagocytophilum is an obligate intracellular bacterium that invades
      neutrophils to cause the emerging infectious disease human granulocytic
      anaplasmosis. A. phagocytophilum undergoes a biphasic developmental cycle,
      transitioning between an infectious dense-cored cell (DC) and a noninfectious
      reticulate cell (RC). To gain insights into the organism's biology and
      pathogenesis during human myeloid cell infection, we conducted proteomic analyses
      on A. phagocytophilum organisms purified from HL-60 cells. A total of 324
      proteins were unambiguously identified, thereby verifying 23.7% of the predicted
      A. phagocytophilum proteome. Fifty-three identified proteins had been previously
      annotated as hypothetical or conserved hypothetical. The second most abundant
      gene product, after the well-studied major surface protein 2 (P44), was the
      hitherto hypothetical protein APH_1235. APH_1235 homologs are found in other
      Anaplasma and Ehrlichia species but not in other bacteria. The aph_1235 RNA level
      is increased 70-fold in the DC form relative to that in the RC form.
      Transcriptional upregulation of and our ability to detect APH_1235 correlate with
      RC to DC transition, DC exit from host cells, and subsequent DC binding and entry
      during the next round of infection. Immunoelectron microscopy pronouncedly
      detects APH_1235 on DC organisms, while detection on RC bacteria minimally, at
      best, exceeds background. This work represents an extensive study of the A.
      phagocytophilum proteome, discerns the complement of proteins that is generated
      during survival within human myeloid cells, and identifies APH_1235 as the first
      known protein that is pronouncedly upregulated on the infectious DC form.

PMID- 21844239
TI  - Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in
      polymorphonuclear leukocytes.
AB  - The human pathogen Neisseria gonorrhoeae recruits and interacts extensively with
      polymorphonuclear leukocytes (PMNs) during infection. N. gonorrhoeae is able to
      survive the bactericidal activity of these innate immune cells and can actively
      modulate PMN functions in vitro. PMNs are short-lived cells which readily undergo
      apoptosis, and thus the effect of N. gonorrhoeae infection on PMN survival has
      implications for whether PMNs might serve as an important site of bacterial
      replication during infection. We developed and validated an HL-60 myeloid
      leukemia cell culture model for PMN infection and used both these cells and
      primary PMNs to show that N. gonorrhoeae infection alone does not induce
      apoptosis and furthermore that N. gonorrhoeae can inhibit both spontaneous
      apoptosis and apoptosis induced by the intrinsic and extrinsic apoptosis inducers
      staurosporine (STS) and tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL), respectively. N. gonorrhoeae infection also results in the
      activation of NF-kappaB signaling in neutrophils and induces secretion of an
      identical profile of proinflammatory cytokines and chemokines in both HL-60 cells
      and primary PMNs. Our data show that the HL-60 cell line can be used to
      effectively model N. gonorrhoeae-PMN interactions and that N. gonorrhoeae
      actively inhibits apoptosis induced by multiple stimuli to prolong PMN survival
      and potentially facilitate bacterial survival, replication, and transmission.

PMID- 21844241
TI  - Small bowel feeding tube placement using an electromagnetic tube placement
      device: accuracy of tip location.
AB  - BACKGROUND: An electromagnetic tube placement device (ETPD) monitors tip position
      of feeding tubes (FT) during placement in the digestive tract. It helps to avoid
      airway misplacement and permits positioning into the small bowel (SB). This study
      compares the overall agreement between FT tip location as determined by an ETPD
      vs an abdominal radiograph of the kidneys, ureter, and bladder (KUB). METHODS:
      Using an ETPD, A nurse placed postpyloric FTs in ICU patients. We included all
      patients in whom the ETPD was used for FT placement. Data were prospectively
      recorded for 255 days on the rate of successful postpyloric placement, ETPD
      estimated tip location, and KUB location. RESULTS: 860 tubes were placed in 616
      patients, 719 (83.6%) of which recorded for ETPD and KUB. According to the KUB,
      81% of tubes were in the SB; however, ETPD suggested 89% were beyond the pylorus.
      There was moderate agreement beyond what could be attributed to chance between
      KUB and ETPD tip locations (475 [66.1%], kappa score 0.62 [95% confidence
      interval 0.58-0.67]). More tubes by KUB were distal (134[18.6%]) vs proximal
      (110[15.3%]) to the suspected location by ETPD (P < .0001. Tubes in or distal to
      the second half of the duodenum, according to ETPD were rarely in the stomach
      (<1%). No tubes were proximal to the stomach or placed into the airway.
      CONCLUSIONS: The strong agreement between KUB and ETPD, when tubes were believed
      to be in the second part of the duodenum or beyond, suggests that KUB is
      necessary only when the FT tip is suspected to be in the proximal duodenum.

PMID- 21844240
TI  - The phosphoinositide-3-kinase-Akt signaling pathway is important for
      Staphylococcus aureus internalization by endothelial cells.
AB  - Internalization of Staphylococcus aureus in bovine endothelial cells (BEC) is
      increased by tumor necrosis factor alpha stimulation and NF-kappaB activation.
      Because the phosphoinositide-3-kinase (PI3K)-Akt signaling pathway also modulates
      NF-kappaB activity, we considered whether the internalization of S. aureus by BEC
      is associated with the activity of PI3K and Akt. We found a time- and
      multiplicity of infection-dependent phosphorylation of Akt on Ser473 in BEC
      infected with S. aureus. This phosphorylation was inhibited by LY294002 (LY),
      indicating the participation of PI3K. Inhibition of either PI3K with LY or
      wortmannin, or Akt with SH-5, strongly reduced the internalization of S. aureus.
      Transfection of BEC with a dominant-negative form of the Akt gene significantly
      decreased S. aureus internalization, whereas transfection with the constitutively
      active mutant increased the number of internalized bacterium. Inhibition of PDK1
      activity with OSU-03012 did not affect the level of S. aureus internalization,
      demonstrating that phosphorylation of Akt on Thr308 is not important for this
      process. Compared to the untreated control, the adherence of S. aureus to the
      surface of BEC was unaltered when cells were transfected or incubated with the
      pharmacological inhibitors. Furthermore, Akt activation by internalized S. aureus
      triggered a time-dependent phosphorylation of glycogen synthase kinase-3alpha
      (GSK-3alpha) on Ser21 and GSK-3beta on Ser9 that was partially inhibited with SH
      5. Finally, treatment of BEC with LY prior to S. aureus infection inhibited the
      NF-kappaB p65 subunit phosphorylation on Ser536, indicating the involvement of
      PI3K. These results suggest that PI3K-Akt activity is important for the
      internalization of S. aureus and phosphorylation of GSK-3alpha, GSK-3beta, and NF
      kappaB.

PMID- 21844242
TI  - Parental follow-through of neuropsychological recommendations for childhood
      cancer survivors.
AB  - In the past 40 years, outcomes for children with cancer have changed
      considerably. The survival rate has increased to approximately 80%. With success
      and survival come detriments that often occur over time called late effects of
      cancer treatment. When the central nervous system is treated with radiation or
      chemotherapy, we often see impairment to the senses, cognition, and learning. For
      children who receive central nervous system treatment, follow-up with a
      neuropsychological evaluation is an excellent tool to evaluate learning and
      behavior in relationship to a child's brain. The authors' research examined
      neuropsychological evaluations for common themes related to diagnosis, age, sex,
      and/or treatment received, and the authors investigated whether the families
      implemented recommendations suggested in the neuropsychological evaluation. Less
      than 50% of recommendations from evaluations were implemented. The authors found
      that families need ongoing support and knowledge to implement the
      neuropsychological testing recommendations. Families need assistance navigating
      the school system and advocating for their child's needs. Continued surveillance
      of the child's academic needs by both the psychology and oncology teams is
      essential for long-term success.

PMID- 21844243
TI  - Psychometric and clinical assessment of the 13-item reduced version of the
      fatigue scale-adolescent instrument.
AB  - Fatigue is one of the most common and distressing symptoms experienced by
      adolescents during and after treatment for cancer. The lack of reliable and valid
      instruments has prevented an accurate assessment of the trajectory of fatigue
      among adolescent oncology patients. The purposes of this study were to identify
      the items on the Fatigue Scale-Adolescent (FS-A) that distinguished adolescents
      with high fatigue and to identify the most sensitive and specific score ("cut
      score") in order to identify those in need of a fatigue intervention. Rasch
      methods were used to identify FS-A items that distinguished adolescents with high
      cancer-related fatigue, and results indicated that the 14-item FS-A could be
      reduced to 13 items. The 13-item FS-A was assessed for its psychometric
      properties, with application of the receiver operating characteristics curve
      analysis to the responses from 75 adolescents. The internal consistency
      coefficient was .87, and a 4-factor confirmatory analysis achieved good fit
      coefficients. The identified cut score was 31, with 66.6% sensitivity and 82.6%
      specificity; 16 (21.33%) of the patients scored 31 or higher. The 13-item FS-A
      has acceptable psychometric properties and is able to identify adolescent
      oncology patients with high fatigue.

PMID- 21844245
TI  - Attitudes and health beliefs associated with breast cancer screening behaviors
      among Turkish women.
AB  - PROBLEM: This research was undertaken to determine the attitudes and health
      beliefs of a sample of Turkish women about breast self-examination (BSE),
      clinical breast examination, and mammography. DESIGN: Data were collected by
      means of a researcher-designed questionnaire and the Champion Health Belief Model
      Scale. A total of 1,342 women participated in this study. RESULTS: It was found
      that 10.1% of the women practiced BSE once a month, 19.8% of the women had had a
      clinical breast examination, and 15.0% had had a mammogram. Age and marital
      status were significant variables that influenced whether the women used only one
      or multiple methods for early detection of breast cancer. Participants who had
      higher levels of confidence for BSE and lower perceptions of barriers to BSE were
      more likely to perform BSE. Participants who perceived higher levels of
      confidence to perform BSE were more likely to be using all three early detection
      methods. IMPLICATIONS FOR PRACTICE: Interventions and strategies that help women
      develop confidence in their abilities to perform early breast cancer detection
      methods are likely to encourage them to engage in regular screening for breast
      cancer.

PMID- 21844246
TI  - Cultural safety as an ethic of care: a praxiological process.
AB  - New writings broadening the construct of cultural safety, a construct initiated
      in Aotearoa New Zealand, are beginning to appear in the literature. Therefore, it
      is considered timely to integrate these writings and advance the construct into a
      new theoretical model. The new model reconfigures the constructs of cultural
      safety and cultural competence as an ethic of care informed by a postmodern
      perspective. Central to the new model are three interwoven, co-occurring
      components: an ethic of care, which unfolds within a praxiological process shaped
      by the context. Context is expanded through identifying the three concepts of
      relationality, generic competence, and collectivity, which are integral to each
      client-nurse encounter. The competence associated with cultural safety as an
      ethic of care is always in the process of development. Clients and nurses engage
      in a dialogue to establish the level of cultural safety achieved at given points
      in a care trajectory.

PMID- 21844244
TI  - Physical, mental, and neurocognitive status and employment outcomes in the
      childhood cancer survivor study cohort.
AB  - INTRODUCTION: We examined the relationship of physical, mental, and
      neurocognitive function with employment and occupational status in the Childhood
      Cancer Survivor Study. METHODS: We included survivors 25 years or older with
      available short form-36 (physical and mental health component scores), brief
      symptom inventory (depression, anxiety, and somatization), and neurocognitive
      questionnaire (task efficiency, emotional regulation, organization, and memory).
      We generated relative risks (RR) from generalized linear models for these
      measures on unemployment (n = 5,386) and occupation (n = 3,763) outcomes adjusted
      for demographic and cancer-related factors and generated sex-stratified models.
      RESULTS: Poor physical health was associated with an almost eightfold higher risk
      of health-related unemployment (P < 0.001) compared to survivors with normal
      physical health. Male survivors with somatization and memory problems were
      approximately 50% (P < 0.05 for both) more likely to report this outcome, whereas
      task efficiency limitations were significant for both sexes (males: RR = 2.43, P
      < 0.001; females: RR = 2.28, P < 0.001). Employed female survivors with task
      efficiency, emotional regulation, and memory limitations were 13% to 20% (P <
      0.05 for all) less likely to work in professional or managerial occupations than
      unaffected females. CONCLUSIONS: Physical problems may cause much of the health
      related unemployment among childhood cancer survivors. Whereas both male and
      female survivors with neurocognitive deficits--primarily in task efficiencies-
      are at risk for unemployment, employed female survivors with neurocognitive
      deficits may face poor occupational outcomes more often than males. IMPACT:
      Childhood cancer survivors are at risk for poor employment outcomes. Screening
      and intervention for physical, mental, and neurocognitive limitations could
      improve employment outcomes for this population.

PMID- 21844247
TI  - Social justice: a framework for culturally competent care.
AB  - Nurse scholars with expertise in global health and culturally competent care
      recently proposed standards of practice for culturally competent nursing care
      that are founded on social justice as a broad framework. The purpose of this
      article is to respond to invited dialogue about the standards and to offer
      commentary on social justice and its relationship with context, advocacy,
      leadership, and culturally competent care. A model of culturally competent care
      for vulnerable groups informs this discussion. The context and culture that
      surround migrant and seasonal farmworkers illustrate how social justice
      illuminates their health inequities and necessitates their need for culturally
      competent care. The article concludes with recommendations for culturally
      competent education, practice, and research and offers suggestions for developing
      culturally competent interventions for migrant and seasonal farmworkers.

PMID- 21844248
TI  - Advances in assessment and management of carotid body tumors.
AB  - Evolving technology has the potential to alter the overall management of carotid
      body tumors (CBTs). We review our 35-year experience emphasizing on novel
      modalities available in the evaluation and treatment of CBTs. Medical records of
      27 CBT patients between 1975 and 2009 were retrospectively reviewed. The study
      cohort has been arbitrarily divided into two groups: the early years' group A (18
      patients, 1975-1998) and the later years' group B (9 patients, 1999-2009). The
      most common presenting symptom was a painless lateral neck mass (89%). Octreotide
      scintigraphy and genetic testing were routinely used for group B. In two cases,
      octreotide scintigraphy was coupled with intraoperative radiolocalization of the
      lesion. Preoperative embolization was performed in four CBTs. Among group B
      patients, five were pretreated via a covered stent placement in the external
      carotid artery (ECA). Twenty-three patients (24 CBTs) were eventually operated
      upon. One cardiovascular death, one permanent vocal cord paralysis and six
      transient cranial nerve injuries account for a 4.4% 30-day mortality and a 30.4%
      morbidity with no significant differences among groups. In conclusion,
      appropriate use of new techniques in CBT management has improved diagnostic
      accuracy and early detection without clearly affecting overall outcome in our
      study cohort.

PMID- 21844249
TI  - Redirected behavior in learning tasks: the commercial laying hen (Gallus gallus
      domesticus) as model.
AB  - Redirected behaviors occur when some course of action is thwarted or inhibited
      (frustration). They also occur as adjunctive behaviors in operant conditioning
      tasks, where they might reflect frustration about unrewarded responses. Because
      frustration is associated with stress, which could interfere with learning and
      memory, we studied whether the occurrence of redirected behavior is correlated
      with learning success in a series of visual-cue discrimination tasks. Eleven
      hens, aged 34 wk, were tested on acquisition, reversal, extinction, and
      relearning of a simple visual discrimination task. The experimenters randomly
      assigned red and blue cardboard discs as discriminative stimuli. A correct
      response was recorded when a hen pecked at the correct disc. The learning
      criterion was 90% correct responses in 20 trials in 2 consecutive task sessions.
      The following data were documented: number of pecks needed to achieve the
      learning criterion, latency in choosing, pecks at the experimenter, and pecks at
      the surroundings. The behavioral responses were analyzed using linear mixed model
      ANOVA. Redirected pecking at the surroundings was a significant indicator of
      learning failure in that the more the hens performed this behavior, the more
      trials they needed to complete the discrimination tasks (P = 0.012). The number
      of pecks at the experimenter during the tasks significantly influenced learning
      success (P = 0.020), with hens directing more pecks at the experimenter during
      reversal, reaching the learning criterion in fewer trials (P = 0.027). The more
      the hens pecked at the experimenter during acquisition and extinction, however,
      the more trials they needed to meet the learning criteria (acquisition: P =
      0.048; extinction: P = 0.003). Thus, laying hens are susceptible to the effects
      of frustration as measured in terms of redirected pecking elicited by operant
      procedures in visual discrimination tasks. In general, any situation in which a
      desirable goal is obstructed or an expected reward is omitted may lead to
      frustration-related activities, such as redirected behavior, which could in turn
      lead to abnormal behavior and welfare issues for the animals.

PMID- 21844250
TI  - Effects of incubation temperature on the bone development of broilers.
AB  - Manipulating the development of the leg bone by making simple changes to
      incubation temperature could help reduce the incidence of abnormalities. This
      study tested the hypothesis that increasing or decreasing the temperature of
      chick incubation by 1 degrees C for 3 d during ED 4 to 7 affects hatchability,
      growth, and leg abnormalities of Cobb 500 broilers fed 3 diets: a diet that
      induced tibial dyschondroplasia, a Ca-deficient diet that induced rickets, and a
      P-deficient diet that induced rickets. In experiment 1, eggs hatched earlier, and
      more eggs hatched, at 38.5 degrees C (92.77%) compared with at 37.5 degrees C
      (86.22%). Body weight was lower in chicks incubated at the higher temperature
      compared with those incubated at the lower temperature (44.66 vs. 42.92 g). In
      experiment 2, egg setting times were +17 h for 36.5 degrees C eggs and -10 h for
      38.5 degrees C compared with standard setting at 37.5 degrees C (508 h).
      Hatchability of fertile eggs (92.92%) was highest at 37.5 degrees C and decreased
      at 36.5 degrees C (89.82%) and 38.5 degrees C (81.55%). Body weight was lower
      (48.98 g) at 36.5 degrees C than at 37.5 degrees C (49.57 g) and at 38.5 degrees
      C (50.56 g). Experiment 3 separated effects of incubation temperature and
      incubation time and was conducted with control and Ca-deficient diets. No main
      effects or interactions between incubation temperature or time and bone
      abnormalities were detected. It is important to note that eggs hatched at
      different times in this study. A difference as little as 1 degrees C for 3 d
      during ED 4 to 7 affected hatching time and weight.

PMID- 21844251
TI  - Effects of stocking density on the growth performance and digestive microbiota of
      broiler chickens.
AB  - Increased stocking densities are frequently reported to depress chicken growth
      performance, but the mechanisms behind this are not fully understood. This study
      was conducted to investigate the effects of stocking density on growth
      performance and digestive microbiota, known to be sensitive to environmental
      factors. Chickens were reared at 2 stocking densities, 12 or 17 birds/m(2).
      Growth performance was recorded between d 1 and 39, and litter was scored for
      quality on d 25, 31, and 37. Digestive microbiota was analyzed along the
      digestive tract (crop, ileum, ceca) of 3- and 6-wk-old chickens by using 2
      molecular approaches: a qualitative method (fingerprinting by temporal
      temperature gradient gel electrophoresis) and a quantitative method (real-time
      PCR). An increase in stocking density was found to negatively affect the feed
      conversion ratio (+3.1%) and depress the daily BW gain of broilers (-5.5%) during
      the period from d 32 to 39 (P <= 0.05). Litter quality was reduced with the high
      stocking density as early as d 25. At 3 wk of age, stocking density strongly
      affected the fingerprint profiles of the bacterial community, with the highest
      modifications observed in the crop and ceca (R analysis of similarity = 0.77 and
      0.69, respectively, P <= 0.05). At 6 wk of age, significant differences in the
      fingerprint profiles between the stocking densities appeared in the crop and ceca
      (R analysis of similarity = 0.52 and 0.27, respectively, P <= 0.05). The
      abundance of bacterial groups targeted by real-time PCR was affected by stocking
      density, but only to a limited extent. Because digestive microbiota may have
      consequences on the physiology of the digestive tract, its modification by an
      increase in stocking density may be involved in the reduced growth performance of
      the bird.

PMID- 21844252
TI  - Heat and moisture production by broilers during simulated cold weather transport.
AB  - To ensure broiler welfare during winter transport, it is necessary to manage heat
      and moisture accumulation within the transport vehicles. Hence, it is necessary
      to determine heat production (HP) and moisture production (MP) rates under
      representative conditions. An environmental chamber containing a standard
      transport drawer was used. Cold air was drawn from outside the building, warmed
      to the desired temperature, and passed through the drawer at 0.35 m(3)/s.
      Broilers were fasted for 7 h, placed into the drawer, and exposed to test
      conditions within the chamber for 3 h. Air temperature and RH were measured
      upstream and downstream of the insulated bird compartment at 1-min intervals.
      Differences in the paired temperature and RH values were used to calculate
      sensible HP and MP for each 1 min of confinement. Effects of temperatures between
      -8 and -18 degrees C and a control (+20 degrees C) were measured for birds in 2
      conditions. In condition A, there were 15 birds/drawer. Birds were 32 to 33 d old
      and weighed 1.8 kg. Packing density was approximately 27 kg/drawer (31 kg/m(2)).
      In condition B, there were 19 or 22 birds/drawer. The drawers with 19 birds
      contained birds that were 39 to 40 d old that weighed 2.68 kg. In the drawers
      with 22 birds, the birds were 35 to 36 d old and weighed 2.29 kg. In either case,
      the packing density was approximately 50 kg/drawer (59 kg/m(2)). Thus, the birds
      in condition B were bigger, more numerous, and more tightly packed than the birds
      in condition A. Drawers were balanced for sex. At +20 degrees C, HP and MP rates
      were similar to other published values. However, for both conditions, HP and MP
      rates increased with decreasing exposure temperatures. In condition A, HP was
      6.08 +/- 0.43 W/kg and MP was 4.46 g/h per kg at 20 degrees C compared with 87.5
      +/- 10.3 W/kg and 22.08 +/- 5.05 g/h per kg at -15 degrees C. In condition B, HP
      was 8.12 +/- 1.24 W/kg and MP was 5.53 +/- 1.68 g/h per kg at 20 degrees C
      compared with 45.92 +/- 1.95 W/kg and 12.33 +/- 0.22 g/h per kg at -18 degrees C.

PMID- 21844253
TI  - Does early antipredator training increase the suitability of captive red-legged
      partridges (Alectoris rufa) for releasing?
AB  - This study aimed to evaluate the postrelease survival and spatial distribution of
      farm-bred red-legged partridges (Alectoris rufa) that were subject to a
      prerelease training program based on exemplary behavior and alarm calls given by
      adults that acted as experienced demonstrators in simulated predator encounters
      (wooden raptor models and humans). Two groups of partridges were released in this
      study: trained (intensively reared birds accompanied by tutors) and control
      (chicks reared without tutors). Releases were conducted in the fall and winter
      spring during 2 consecutive years using a total of 44 trained and 40 control
      radio-tagged partridges. Trained partridges showed statistically higher mean
      values of survival (72.7 d), home range (13.04 ha), and dispersion (549.58 m)
      compared with nontrained partridges, with most nontrained birds failing to
      survive more than 2 wk after release. Trained adult partridges showed the best
      survival results (105.2 d). Taking all birds into account, causes of death were
      attributed to terrestrial predators (45%), raptors (18.7%), hunting (11.3%), and
      unknown causes (25%). Although values of variables reported here were lower than
      those reported in wild counterparts, survival time and spatial behavior of
      trained birds were close to that of previous data of parent-reared partridges and
      higher than that of farm-bred birds. This study aimed to confirm the potential of
      prerelease training techniques in present-day rearing systems. Farm-bred game
      birds, which normally suffer from high predation rates after release, could
      highly benefit from the use of cost-effective training techniques based on
      learning from experienced adults.

PMID- 21844254
TI  - Quantitative trait loci associated with the humoral innate immune response in
      chickens were confirmed in a cross between Green-Legged Partridgelike and White
      Leghorn.
AB  - Natural antibodies (NA) create a crucial barrier at the initial steps of the
      innate humoral immune response. The main role of NA in the defense system is to
      bind the pathogens at early stages of infection. Different pathogens are
      recognized by the presence of highly conserved antigen determinant [e.g.,
      lipopolysaccharide (LPS) in gram-negative bacteria or lipoteichoic acid (LTA) in
      gram-positive bacteria]. In chickens, a different genetic background of NA binds
      LPS and LTA antigens, encoded by different QTL. The main objective of this work
      was to confirm known QTL associated with LPS and LTA NA. For this purpose a
      chicken reference population was created by crossing 2 breeds: a commercial
      layer, White Leghorn, and a Polish indigenous chicken, Green-Legged
      Partridgelike. The chromosomal regions analyzed harbored to GGA3, GGA5, GGA6,
      GGA8, GGA9, GGA10, GGA14, GGA15, GGA18, and GGAZ. The data collected consisted of
      the NA titers binding LPS and LTA (determined by ELISA at 12 wk of age) as well
      as the genotypes (30 short tandem repeat markers; average of 3
      markers/chromosome, collected for generations F(0), F(1), and F(2)). The analyses
      were performed with 3 statistical models (paternal and maternal half-sib, line
      cross, and linkage analysis and linkage disequilibrium) implemented in GridQTL
      software (http://www.gridqtl.org.uk/). The QTL study of humoral innate immune
      response traits resulted in the confirmation of 3 QTL associated with NA titers
      binding LPS (located on GGA9, GGA18, and GGAZ) and 2 QTL associated with NA
      titers binding LTA (located on GGA5 and GGA14). A set of candidate genes within
      the regions of the validated QTL has been proposed.

PMID- 21844255
TI  - The effect of dietary protein level on performance characteristics of coccidiosis
      vaccinated and nonvaccinated broilers following mixed-species Eimeria challenge.
AB  - A series of experiments were conducted to investigate the effect of starter diet
      protein levels on the performance of broilers vaccinated with a commercially
      available live oocyst coccidiosis vaccine before subsequent challenge with a
      mixed-species Eimeria challenge. Data indicated that an increasing protein
      concentration in the starter diet improved broiler performance during coccidiosis
      vaccination. Prechallenge performance data indicated that vaccination could
      decrease BW and increase feed conversion ratio. The time period most important
      for the observed effects appeared to be between 13 and 17 d of age. This
      reduction in performance parameters of vaccinated broilers compared with
      nonvaccinated broilers was eliminated by the conclusion of the experiments (27 d)
      in the diet groups with higher protein. Vaccination was effective at generating
      protective immunity against Eimeria challenge, as evidenced by increased (P <
      0.05) BW gain, improved feed conversion, reduced postchallenge mortality, and
      reduced lesion development in vaccinated broilers compared with nonvaccinated
      broilers. These observations support numerous other reports that confirm live
      oocyst vaccination can be used effectively as a preventive against avian
      coccidiosis in commercially reared broilers. More important, these findings
      suggest that reduced protein concentration of starter diets can lead to
      significant losses in broiler performance when using a vaccination program to
      prevent coccidiosis.

PMID- 21844256
TI  - Conjugated linoleic acids alleviate infectious bursal disease virus-induced
      immunosuppression in broiler chickens.
AB  - The immunoregulatory actions of conjugated linoleic acid (CLA) of relevance to
      viral disease pathogenesis and immune responses were investigated. To test the
      hypothesis that CLA ameliorates immunosuppression, we developed a viral challenge
      model by infecting chickens with infectious bursal disease virus (IBDV). After 14
      d of dietary supplementation with either soybean oil or CLA, half of the chickens
      in each group were challenged with IBDV. We examined the effect of CLA on the
      development of lesions (i.e., lymphoid depletion and necrosis) and observed the
      immune responses against IBDV. The IBDV infection depleted lymphocytes in the
      medullary area and significantly stimulated interferon (IFN)-gamma and IL-6 mRNA
      relative expression of bursa (P < 0.05) compared with the uninfected bursa.
      Compared with the CLA diet, lymphocytes depletion was more accentuated in
      chickens fed the control diet, whereas IFN-gamma and IL-6 mRNA relative
      expression were upregulated (P < 0.05). Additionally, histopathological
      examination of the bursa revealed that the pathological changes tended to be more
      severe in infected chickens fed the control diet, which also significantly
      decreased (P < 0.05) on lymphocyte proliferation. Significant interactions were
      found between infection and diets for lymphocyte proliferation, antibody titers,
      and IFN-gamma mRNA relative expression (P < 0.05). The results of this study
      indicate that dietary CLA enhanced immune function in chickens, particularly
      those of the IBDV-immunosuppressive status. Furthermore, at the molecular level,
      the immunoregulatory functions of CLA on chickens are attributable mainly to the
      antiinflammatory properties of CLA and are mediated, at least in part, through
      suppressing IBDV-specific proinflammatory cytokines mRNA relative expression.

PMID- 21844257
TI  - Meta-analytical study of productive and nutritional interactions of mycotoxins in
      broilers.
AB  - A meta-analysis was carried out to study the association of mycotoxins with
      performance, productive indices, and organ weights in broilers. Ninety-eight
      papers published between 1980 and 2009 were used, totaling 1,401 diets and 37,371
      animals. Meta-analysis followed 3 sequential analyses: graphical, correlation,
      and variance-covariance. The mycotoxin presence in diets reduced (P < 0.05) feed
      intake by 12% and weight gain by 14% compared with control group. Ochratoxins and
      aflatoxins were the mycotoxins with the greatest effect on feed intake and bird
      growth, reducing (P < 0.05) feed ingestion by 17 and 11%, respectively, and
      weight gain by 20 and 11%, respectively. The mycotoxin concentration in diets and
      the animal age at challenge were the variables that more improved the coefficient
      of determination for equations to estimate mycotoxin effect on weight gain. The
      mycotoxin effect on growth proved to be greater in young poultry. The residual
      analysis revealed that 65% of the variation in weight gain was explained by feed
      intake. The variation in weight gain of challenged broilers in relation to
      nonchallenged broilers was also influenced by ingestion of nutrients such as
      protein and methionine. Mortality was 8.8 and 2.8 times greater (P < 0.05) in
      groups that received diets with deoxynivalenol and aflatoxins, respectively.
      Mycotoxins also increased (P < 0.05) the relative weight of liver by 15%, of
      kidneys by 11%, of lungs by 9%, and of gizzard by 3%. Mycotoxins influenced
      broiler performance, productive indices, and organ weights. However, the
      magnitude of the effects varied with type and concentration of mycotoxin, animal
      age, and nutritional factors.

PMID- 21844258
TI  - Polymorphisms of chicken toll-like receptor 1 type 1 and type 2 in different
      breeds.
AB  - Toll-like receptors (TLR) mediate immune responses via recognition of pathogen
      associated molecular patterns, thus playing important roles in the host defense.
      Polymorphisms of TLR may affect their recognition of pathogen-associated
      molecular patterns, leading to varied host resistance to pathogenic infections.
      However, little is known regarding the polymorphisms of chicken TLR (ChTLR) among
      breeds. In this study, we cloned ChTLR1 type 1 and type 2 genes from 9 chicken
      breeds (2 commercial breeds and 7 Chinese native breeds) and analyzed their
      sequences. We found 27 amino acid polymorphism sites in ChTLR: 14 sites in type 1
      (8 sites in the extracellular domain, 5 sites in the cytoplasmic domain, and 1
      site in the transmembrane domain) and 13 sites in type 2 (11 sites in the
      extracellular domain, 1 site in the cytoplasmic domain, and 1 site in the
      transmembrane domain). These results demonstrate that ChTLR1 type 1 and type 2
      genes are polymorphic among chicken breeds, suggesting a varied resistance among
      breeds of chicken. This information provides new consideration for future poultry
      breeding and breed improvement.

PMID- 21844259
TI  - Characterization of Escherichia coli isolates from laying hens with
      colibacillosis on 2 commercial egg-producing farms in Korea.
AB  - The present study reports on layer chickens with colibacillosis in 2 commercial
      egg-producing farms (referred to as farm A and farm B, which were managed by the
      same owner and were about 1 km apart) in the middle region of the Korean
      peninsula. The 2 flocks were infected at the initiation of egg laying. They were
      characterized by no previous clinical signs but sudden mortality (2.7-4.0%), with
      severe lesions of septicemia and fibrinous polyserositis. Escherichia coli was
      isolated from the lesions of the infected birds. Serotyping tests identified
      isolates that belonged to somatic groups O1 (12/17), O46 (2/17), O78 (1/17), and
      O84 (1/17) or that were unidentified (1/17). Thirteen of 17 E. coli isolates
      (76.4%) obtained from 11 birds in the 2 flocks showed similar pulsed-field gel
      electrophoresis patterns that were arbitrarily designated as pattern A. The
      isolates had high frequencies of putative virulence genes including 100% [fimC
      (type 1 fimbriae), iucD (aerobactin synthesis), and iss (increased serum
      survival)], 94.1% [cva/cvi (structural genes of colicin V operon) and vat
      (vacuolating autotransporter toxin)], 88.2% [irp2, iron-repressible protein
      (yersinia bactin) synthesis, and fyuA, ferric yersinia uptake], and 82.3% [tsh
      (temperature-sensitive hemagglutinin)]; astA (encoding a heat-stable cytotoxin
      associated with enteroaggregative E. coli) was not associated with the enteric
      disorder. These data suggest that all chickens with colibacillosis on farms A and
      B were likely infected by E. coli strains that are highly pathogenic in avian
      species.

PMID- 21844260
TI  - Enhancement of humoral immune responses to inactivated Newcastle disease and
      avian influenza vaccines by oral administration of ginseng stem-and-leaf saponins
      in chickens.
AB  - Newcastle disease (ND) and avian influenza (AI) are common in the poultry
      industry. The objective of this study was to evaluate the effect of oral
      administration of ginseng stem-and-leaf saponins (GSLS) on the humoral immune
      responses of chickens to inactivated ND and AI vaccines. In experiment 1, oral
      administration of GSLS at a dose of 5 mg/kg of BW for 7 d on the immune response
      in chickens intramuscularly injected with inactivated ND vaccine was evaluated.
      Results showed that GSLS significantly increased the antibody level against ND in
      the serum of chickens. In experiment 2, the same regimen of GSLS was administered
      to chickens inoculated with inactivated AI vaccines, and an enhanced serum
      antibody response to AI vaccination was also observed. Considering the safety of
      GSLS, because no adverse effect was found throughout the experiments, GSLS may be
      a promising oral adjuvant to improve immunization in poultry.

PMID- 21844261
TI  - Dried distillers grains with solubles in laying hen diets.
AB  - A study was conducted to test the inclusion rate of corn dried distillers grains
      with solubles (DDGS) in laying hen diets on egg production (EP) responses for a
      full production cycle. A total of 288 Bovan Single Comb White Leghorn laying hens
      were fed diets containing 0, 5, 10, 15, 20, or 25% DDGS from 24 to 46 wk (phase
      1) and 47 to 76 wk (phase 2) of age. The diets were formulated to be isocaloric
      at 2,775 and 2,816 kcal/kg of ME and isonitrogenous at 16.5 and 16.0% CP for
      phases 1 and 2, respectively. Nutrient retention of both N and P were determined
      by the indicator methods during phase 2. Diets were replicated with 8
      pens/treatment and 6 hens/pen in an unbalanced randomized complete block design.
      Average daily feed intake, EP, and overall weight gain were similar (P = 0.08 to
      0.1) among treatments during the study. Egg weight was affected (P = 0.064) by
      DDGS treatment during phase 1. Hens fed 0, 5, 10, 15, 20, or 25% DDGS had an
      average egg weight of 60.6, 60.4, 60.8, 60.0, 59.0, and 59.0 g, respectively;
      however, no differences were detected in egg weight during phase 2. During phase
      1, diets were formulated based on TSAA, allowing Met to decrease as DDGS
      increased, but during phase 2, diets were formulated to keep Met equal across
      DDGS treatments, allowing TSAA to increase as a result of high Cys in DDGS. Yolk
      color increased with increasing DDGS level; the highest Roche score (P = 0.001)
      was 7.2 for hens fed 25% DDGS. Nitrogen and P retention was greater (P = 0.003)
      in hens fed 25% DDGS. Also, N and P excretion decreased (P = 0.007) linearly as
      DDGS increased. In summary, feeding DDGS up to 25% during EP cycles had no
      negative effects on feed intake, EP, Haugh units, or specific gravity, and
      improved yolk color at the highest levels. Increasing DDGS level beyond 15%
      caused a reduction in egg weight during phase 1 of egg production, though no
      differences were observed in egg weight during phase 2. Nitrogen and P excretion
      were lower at higher inclusion rate of DDGS. Hens fed 25% DDGS had the highest N
      and P retention.

PMID- 21844262
TI  - The effects of dietary fluoride on growth and bone mineralization in broiler
      chicks.
AB  - Fluoride has been shown to have varying degrees of beneficial effects on bone
      mineralization and bone strength, despite its toxic effects on growth and leg
      disorders. Some studies have demonstrated an increase in bone ash resulting from
      F supplementation. The purpose of the present study was to determine whether low
      levels of dietary F would have any beneficial effect on the bone strength and leg
      disorders of young chicks fed P-deficient diets. Effects on BW and feed
      efficiency were also observed to monitor for F toxicity. One-day-old straight-run
      Cobb * Cobb broiler chicks were weighed, randomly allocated to treatment groups,
      housed in electrically heated wire-floored battery brooders, and provided with
      water and feed for ad libitum consumption. Phosphorus-deficient diets were
      formulated to induce P rickets with 2 different P sources. Treatment 1 contained
      feed grade dicalcium phosphate to simulate a commercial diet. Treatment 2
      contained purified dicalcium phosphate to represent a diet with minimal F (~0.46
      mg/kg). Treatments 3 and 4 used purified dicalcium phosphate as the P source and
      contained 10 and 20 mg/kg of F from NaF, respectively. Four more treatments were
      added for experiment 2. Treatments 5, 6, 7, and 8 used purified dicalcium
      phosphate as the P source and contained 30, 40, 50, and 60 mg/kg of F from NaF,
      respectively. The analyzed F values in the diet were lower than the formulated
      values as a result of an unexplained lower than desired rate of recovery (72%) of
      an internal standard. Chicks fed purified calcium phosphate grew better in
      experiment 1 (P < 0.05) and had a lower incidence of P-deficiency rickets in
      experiment 2 (P < 0.01) than did birds fed feed grade dicalcium phosphate.
      Percentage of bone ash was increased by increasing the F level in the diets in
      experiment 1, but not experiment 2. It was concluded that even low levels of F,
      such as those used in the present study, have the potential to increase bone
      quality.

PMID- 21844263
TI  - Effects of xylanase and citric acid on the performance, nutrient retention, and
      characteristics of gastrointestinal tract of broilers fed low-phosphorus wheat
      based diets.
AB  - An experiment was conducted to study the effects of xylanase and citric acid on
      the performance, nutrient retention, jejunal viscosity, and size and pH of the
      gastrointestinal tract of broilers fed a low-P wheat-based diet. The experiment
      was conducted as a 2 * 3 factorial arrangement with 2 levels of xylanase (0 and
      200 mg/kg) and 3 levels of citric acid (0, 20, and 40 g/kg). Each of the 6
      dietary treatments was fed to 4 replicate pens (17 birds/pen) from 0 to 24 d of
      age. Chromium oxide (3 g/kg) was added to the diets as an indigestible marker to
      determine the apparent nutrient retention. No interaction effect was observed
      between xylanase and citric acid in any measured response. Xylanase did not
      affect feed intake but significantly increased BW gain by 3.6% (P < 0.05) from 1
      to 24 d of age and improved G:F by 3.9% (P < 0.01). The inclusion of 40 g/kg of
      citric acid decreased (P < 0.01) BW gain and feed intake by 8.6 and 12.5%,
      respectively. The inclusion of 20 and 40 g/kg of citric acid improved G:F by 2.3
      and 4.5% (P < 0.05), respectively. Xylanase significantly decreased the viscosity
      of digesta and improved the retention of DM, CP, and energy, but did not have a
      significant effect on the retention of fat and P. Inclusion of 20 and 40 g/kg of
      citric acid in the diets increased P retention by 15.8 and 16.3% (P < 0.01),
      respectively. Citric acid significantly decreased the pH of crop contents (P <
      0.05). In conclusion, citric acid, at the 40 g/kg inclusion level, reduced feed
      intake and BW gain but improved G:F and P retention. Xylanase decreased digesta
      viscosity, increased nutrient retention, and consequently improved the
      performance of broilers fed the low-P wheat-based diet. Thus, adding 20 g/kg of
      citric acid, especially in the starter period, and 200 mg/kg of xylanase to low-P
      wheat-based diets can be helpful.

PMID- 21844264
TI  - Evaluation of an indigenous source of rock phosphate as a supplement for broiler
      chickens.
AB  - This study investigated the effects of replacing dicalcium phosphate (DCP) with
      Hazara rock phosphate (HRP) on the growth performance of broiler chickens. The
      purpose was to determine the maximum level of F that could be well tolerated. The
      HRP (13.16% P and 2.98% F) was incorporated into a standard corn- and soybean
      meal-based diet by replacing 0, 25, 50, 75, and 100% of DCP based on P. Each
      treatment consisted of 5 replicate pens of 10 chicks each. The Ca and nonphytate
      P contents of all diets were maintained constant at 1.0 and 0.45%, respectively.
      Replacing 25% DCP with HRP significantly increased average BW gain. Substituting
      100% HRP (562 mg of F/kg) decreased (P < 0.05) BW gain. The BW gain was maximized
      at 63.5:36.5 (DCP:HRP) using a quadratic relationship: BW gain (g) = 1,128.6 +
      2.6848 * HRP - 0.0368 * HRP(2). Increasing the level of HRP decreased feed
      intake: feed intake (g) = 1,987.4 + 2.775 * HRP - 0.0515 * HRP(2). The effect of
      HRP was not pronounced (significant at P < 0.05) until 75% of DCP was replaced by
      HRP. Feed intake decreased by an average 3.77 g with each 1.0% increase in the
      levels of HRP beyond 27% HRP substitution. Replacing DCP with HRP up to 50%
      caused a significant increase in hot carcass weights. The Ca content of tibia was
      a quadratic function of HRP and was predicted to be highest at 56% HRP
      substitution. However, increasing HRP in the diet gradually decreased tibia P
      content (linear function). Serum Ca was increased by substituting HRP for DCP
      (linear effect). Increasing HRP in the diet decreased the P content of the serum
      and was predicted to be lowest (P < 0.05) beyond 50% HRP substitution, suggesting
      poor P availability at high HRP. In conclusion, growth was maximized by feeding
      about 36.5% HRP (205 mg of F/kg) and 63.5% DCP as P supplements. Using a multiple
      range test, it was concluded that between 25 and 50% DCP with HRP replacement
      (141 and 281 mg of F/kg, respectively) could be used safely without significantly
      decreasing the growth performance of broiler chickens.

PMID- 21844265
TI  - Effects of the free fatty acid content in yellow grease on performance, carcass
      characteristics, and serum lipids in broilers.
AB  - This study was conducted to investigate whether the free fatty acid (FFA) content
      of yellow grease would influence the performance and carcass characteristics of
      broiler chicks. A total of 432 one-day-old, male Arbor Acres broilers were
      randomly allotted to 1 of 4 treatments, with each treatment being applied to 6
      pens of 18 chicks. The dietary treatments were based on corn and soybean meal and
      were supplemented with either soybean oil (2.86% FFA) or yellow grease with a low
      (2.74%), medium (12.59%), or high (19.05%) FFA content. The fat sources were
      supplemented at 1.5% of the diet during the starter phase (0 to 21 d) and at 3.0%
      of the diet during the grower phase (22 to 42 d). From d 0 to 42, the BW gains of
      chicks fed diets containing soybean oil and yellow grease with 2.74% FFA were
      similar. As the FFA level in the yellow grease increased, the BW gain of chicks
      decreased (P < 0.01). The reduction in BW gain appeared to be mediated by a
      reduction in feed intake. The dressing percentage and the percentage of breast
      muscle in the carcass were significantly (P < 0.01) lower for broilers fed any
      yellow grease diet compared with birds fed soybean oil. In contrast, abdominal
      fat was significantly increased in diets containing yellow grease. These results
      demonstrate that the performance of birds fed yellow grease with a low content of
      FFA was essentially equal to that of birds fed soybean oil. However, because
      yellow grease samples containing FFA levels greater than 2.74% negatively
      affected bird performance, producers should exercise caution with regard to
      feeding broilers yellow grease with an elevated FFA content. In 42-d-old
      broilers, serum total cholesterol and low-density lipoprotein cholesterol levels
      were elevated in birds fed yellow grease, regardless of the dietary level. In
      contrast, serum high-density lipoprotein cholesterol and triglyceride levels were
      unaffected by dietary treatment. Although dietary FFA may influence triglyceride
      rich lipoprotein metabolism in broilers, an explanation for the observed effects
      remains elusive.

PMID- 21844266
TI  - Energy determination of corn co-products fed to broiler chicks from 15 to 24 days
      of age, and use of composition analysis to predict nitrogen-corrected apparent
      metabolizable energy.
AB  - An experiment (3 trials) was conducted to determine the AME(n) of 15 corn co
      products obtained from various wet and dry milling plants, and to develop
      prediction equations for AME(n) based on chemical composition. Co-products
      included distillers dried grains with solubles (DDGS, n = 6), high-protein
      distillers dried grains (n = 2), corn germ (n = 2), corn germ meal, corn bran
      with solubles, corn gluten meal, corn gluten feed, and dehulled, degermed corn.
      Treatments (15) consisted of 85% inclusion of the corn-soybean meal basal diet
      combined with a 15% inclusion of each corn co-product, as well as a control diet
      containing glucose*H(2)O (15%) at the expense of the co-product. In each trial,
      Ross * Ross 708 chicks (10 birds per pen) were randomly assigned to 16 dietary
      treatments (12 replicate pens; 4 replicate pens per trial). After a 7-d diet
      acclimation period from 15 to 22 d of age, a 48-h total excreta collection was
      conducted for the determination of AME(n). Co-products were analyzed for gross
      energy, CP, moisture, crude fat, starch, crude fiber, ash, total dietary fiber,
      neutral detergent fiber, and acid detergent fiber, and hemicellulose was
      determined by difference. Stepwise regression resulted in the following equation:
      AME(n), kcal/kg of DM = 3,517 + (46.02 * % crude fat, DM basis) - (82.47 * % ash,
      DM basis) - (33.27 * % hemicellulose, DM basis) (R(2) = 0.89; SEM = 191; P <=
      0.01). Removing hemicellulose from the model resulted in the following equation:
      AME(n), kcal/kg of DM = (-30.19 * % neutral detergent fiber, DM basis) + (0.81 *
      gross energy, kcal/kg of DM basis) - (12.26 * % CP, DM basis) (R(2) = 0.87; SEM =
      196; P <= 0.01). These results indicate that nutrient composition may be used to
      generate AME(n) prediction equations for corn co-products fed to broiler chicks.

PMID- 21844267
TI  - The influence of different levels of micronized insoluble fiber on broiler
      performance and litter moisture.
AB  - The effects of different levels of micronized insoluble fiber (MIF) on broiler
      performance and litter moisture were assessed in 320 one-day-old male broilers
      (Ross 308). Feed was supplemented with 0, 0.3, 0.4, or 0.5% MIF during both the
      starter (1 to 14 d) and grower (15 to 42 d) periods. Supplementation of MIF was
      associated with dose dependent increases in daily BW gain and feed conversion
      ratio throughout the experimental period (P < 0.01), whereas feed intake was not
      influenced by MIF concentration. As MIF content increased, the relative weight of
      digestive organs was not changed (P > 0.05). Supplementation of MIF resulted in
      dose dependent increases in the ileal villus height:crypt depth ratio and number
      of goblet cells (P < 0.05), and a dose dependent decrease in litter moisture
      beginning during the third week (P < 0.01). These findings indicate that
      inclusion of 0.5% MIF in feed resulted in the greatest improvements in broiler
      performance, intestinal morphology, and litter moisture.

PMID- 21844268
TI  - Recent advances in research on enzymes for poultry diets.
AB  - Exogenous enzymes have been used extensively in the diets of poultry to improve
      productive performance. Further research, however, is needed to evaluate the
      efficacy of enzyme use and for the expansion of the use of enzymes to accommodate
      the wide array of dietary constituents used in poultry feeding programs. The use
      of effective phytase preparations to improve bird performance and to reduce
      environmental P pollution has shown less than optimum results, partly due to the
      potential negative effects of nontargeted dietary fiber components and to
      confounding influence of inadequate knowledge of accurate P requirements and the
      tendency for the use of excessive safety margins in diet formulation. Targeting
      specific nonstarch polysaccharides (NSP) of wheat, barley, or rye with enzyme
      preparations has proven effective for diets based on these cereals but not for
      corn- and soybean meal-based diets, primarily due to the differences in
      constituent NSP. The increased use of whole flaxseed in poultry diets represents
      an additional research area for effective enzyme development to alleviate
      potential negative effects of constituent NSP components. Such challenges of the
      enzyme development process and their outcomes are presented in this publication.

PMID- 21844269
TI  - Comparison of adipose tissue cellularity in chicken lines divergently selected
      for fatness.
AB  - After 13 generations of divergent selection for abdominal fatness, 2 chicken
      lines (a fat line and a lean line) have been established. To clarify the cellular
      mechanism underlying the differences in fatness between the fat and lean lines,
      cellularity characteristics of the abdominal adipose tissues were analyzed during
      the first 7 wk of age by electron microscopy, proliferating cell nuclear antigen
      staining, and DNA content measurement. The abdominal fat percentage at 7 wk of
      age in the fat chicken line was 3.8 times that of the lean line, and was
      accompanied by a 1.3-fold increase in adipocyte diameter and a 2.4-fold increase
      in adipocyte number. The total cell number of the abdominal fat pad in the fat
      chicken line was 1.9 times that of the lean line at 7 wk of age. However, no
      significant difference was observed in the proliferation rate of stroma vascular
      fraction cells between the 2 chicken lines. These findings suggest that the
      divergently selected fat and lean chickens have different adipose tissue
      ontogeny.

PMID- 21844270
TI  - Steroid hormone content of seminal plasma influences fertilizing ability of sperm
      in White Leghorns.
AB  - Maternal and paternal influences before fertilization can significantly affect
      the ultimate reproductive output. In avian species, previous studies have shown
      that concentrations of testosterone (T) in seminal plasma vary greatly and are
      related to sperm quality. To our knowledge, the presence of other reproductive
      hormones in avian seminal plasma and their potential influences on fertility
      remain unstudied. We measured the concentrations of progesterone (P4), T,
      dihydrotestosterone, and estrogen in seminal and blood plasma collected from
      White Leghorn roosters. Progesterone was the most abundant hormone compared with
      all others measured, and concentrations of P4 in seminal plasma were
      significantly higher than concentrations found in circulation. Given the
      relatively high concentration of seminal plasma P4, we then attempted to
      determine its effect on fertility. Hens were inseminated with semen samples that
      were supplemented with either a high physiological dose of P4 or a control
      vehicle. Fertilization ability of all semen samples was then characterized using
      a perivitelline sperm hole penetration assay. Progesterone treatment
      significantly decreased the ability of sperm to reach and penetrate the egg,
      suggesting that males that deposit more P4 into seminal plasma may have a
      decreased capability to fertilize an egg.

PMID- 21844271
TI  - Intestinal physiology and regulatory T cell response to immediate or delayed
      access to feed and water in Pekin ducklings.
AB  - This study investigated the effects of delayed access to feed and water on early
      duckling growth, selected aspects of intestinal physiology, and immune responses.
      Ducklings were assigned to one of 2 experimental groups. In one treatment group
      (referred to as the fed group), feed and water were provided beginning on d 0,
      and in the other treatment group (referred to as the withheld group), feed and
      water were withheld until d 2. The ducklings in the withheld treatment had lower
      BW at 2 and 6 d posthatch than ducklings in the fed group. At 8 d posthatch (6 d
      postfeeding), the BW of the ducklings in the withheld group was comparable to the
      BW of the 6-d-old ducklings in the fed group. At 2 d posthatch, withheld
      ducklings had lower absolute and relative duodenum plus pancreas weight than fed
      ducklings. At 8 d posthatch (6 d postfeeding), withheld ducklings had higher
      absolute and relative duodenum plus pancreas weight than fed ducklings at 6 d
      posthatch. At 2 d posthatch, mucin 5B mRNA content was approximately 2 times
      lower in withheld ducklings (P = 0.09) than in fed ducklings. At 6 d posthatch,
      mucin 5b mRNA content was approximately 2.5-fold higher in withheld ducklings (P
      = 0.07) than in fed ducklings. Delayed access to feed and water increased the
      CD25(+) cell number in the cecal tonsil at 2, 6, and 8 d posthatch. The IL-10
      content of CD25(+) cells was higher in the withheld ducklings than in the fed
      ducklings at 2 and 6 d posthatch. In conclusion, delaying access of ducklings
      with no experimental pathogen infection to feed and water has no long-term
      effects on early growth parameters, intestinal physiology, and immune responses.

PMID- 21844272
TI  - Semen cryopreservation for the creation of a Spanish poultry breeds cryobank:
      optimization of freezing rate and equilibration time.
AB  - A sperm cryopreservation protocol requiring dimethylacetamide (DMA, 6%) as a
      cryoprotectant was optimized via assays involving different prefreezing
      equilibration times (1, 10, 30, 60, and 120 min at 5 degrees C) and different
      freezing rates achieved by the following: 1) using nitrogen vapor to reduce the
      temperature from 5 degrees C to -85 degrees C at 10 degrees C/min (slow freezing
      rate); 2) using a biological freezer unit in a 2-step method to reduce the
      temperature from 5 degrees C to -35 degrees C at 7 degrees C/min and then from 
      35 degrees C to -140 degrees C at 60 degrees C/min (medium freezing rate); or 3)
      using a biological freezer unit in a 1-step freezing method to reduce the
      temperature from 5 degrees C to -180 degrees C at 60 degrees C/min (rapid
      freezing rate). Heterospermic semen samples from chicken breeds raised as part of
      a Spanish genetic resource conservation program were used in all assays. The 1
      min equilibration treatment was associated with a lower percentage of viable
      thawed spermatozoa than the 30-min treatment (P < 0.05). The remaining sperm
      variables studied were not affected by equilibration time. The medium-rate 2-step
      freezing method was associated with a higher percentage of motile spermatozoa
      after thawing and with greater acrosome integrity (P < 0.05) than the slow
      nitrogen vapor or rapid 1-step methods. Thawed sperm movement quality and plasma
      membrane integrity (as assessed by the hypoosmotic swelling test) were better (P
      < 0.05) in samples frozen by the medium-rate 2-step freezing method than in those
      subjected to the slow nitrogen vapor method. Fertility was not influenced by
      freezing method, although that achieved with the medium rate 2-step freezing
      method showed a trend toward being greater than that achieved with the rapid 1
      step method (P = 0.07). Together, the present results suggest that slow cooling
      rates are not recommendable when using dimethylacetamide. The 2-step freezing
      method may be useful in the establishment of a germplasm bank for Spanish chicken
      breeds.

PMID- 21844273
TI  - Effects of lipopolysaccharide on the expression of proinflammatory cytokines and
      chemokines and influx of leukocytes in the hen ovary.
AB  - The aim of this study was to determine whether the expression of proinflammatory
      cytokines and chemokines in ovarian cells was changed to recruit heterophils and
      T cells in response to lipopolysaccharide (LPS), a gram-negative bacterial
      component. White Leghorn laying hens were intravenously injected with LPS or
      saline and their ovarian follicles and stroma were collected. Changes in the mRNA
      expression of IL-1beta, IL-6, and CXCLi2 in the theca and granulosa layers and
      ovarian stroma were analyzed by quantitative reverse transcriptase PCR, whereas
      proteins of IL-1beta and IL-6 were also identified by Western blot analysis.
      Localization of heterophil-like cells and CD4(+) and CD8(+) T cells was examined
      by general histology and immunohistochemistry. The expressions of IL-1beta, IL-6,
      and CXCLi2 were significantly increased in the granulosa layer, theca layer, and
      stroma tissues by 3 to 6 h after LPS injection. Increase of IL-1beta and IL-6
      proteins in those tissues was also identified 12 h after LPS injection. The LPS
      stimulation resulted in the increased influx of heterophil-like cells and CD4(+)
      T cells, but not CD8(+) cells, in the theca layers of follicles. Saline injection
      affected neither expression of examined proinflammatory cytokines and chemokines
      nor frequencies of immunocompetent cells. These results suggest that ovarian
      follicular cells and stromal cells have the ability to express proinflammatory
      cytokines and chemokines, and their expression is upregulated by LPS in
      association with the recruitment of heterophil-like cells and T cells. These
      responses may play roles in local host defense in ovarian follicles.

PMID- 21844274
TI  - Comparison of environmental and egg microbiology associated with conventional and
      free-range laying hen management.
AB  - Eggs from alternative production practices are a growing niche in the market.
      Meeting consumer requests for greater diversity in retail egg options has
      resulted in some unique challenges such as understanding the food safety
      implications of eggs from alternative production practices. A study was conducted
      to determine what, if any, differences exist between nest run conventional cage
      produced eggs and free range-produced eggs. A sister flock of brown egg layers
      was maintained in conventional cage and free-range production with egg and
      environmental sampling every 6 wk from 20 to 79 wk of age. Aerobic, coliform, and
      yeast and mold populations were monitored. Environmental microbial levels were
      not always indicative of egg contamination levels. When significant differences
      (P < 0.05 and P < 0.0001, dependent on season) were observed among treatments for
      coliforms, shell contamination levels of free-range nest box eggs and free-range
      floor eggs were always greater than those of conventional cage eggs, which
      remained low throughout the study (0.42-0.02 log cfu/mL). Shell yeast and mold
      levels were significantly greater in free-range floor eggs than in free-range
      nest box eggs and conventional cage eggs throughout the entire study. Egg
      contents contamination levels were extremely low for all monitored populations
      and treatments. Season of the year played a role in both environmental and egg
      microbial levels. Winter had the lowest levels of all populations monitored for
      all treatments, except for aerobic free-range floor egg shell emulsions, which
      were increased (3.6 log cfu/mL). Understanding the differences in microbial
      populations present on conventional cage-produced and free range-produced eggs
      can lead to the development of effective cleaning procedures, enhancing food
      safety.

PMID- 21844275
TI  - Comparison of lipid oxidation, messenger ribonucleic acid levels of avian
      uncoupling protein, avian adenine nucleotide translocator, and avian peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha in skeletal muscles from
      electrical- and gas-stunned broilers.
AB  - The aim of this study was to compare the effects of stunning methods [electrical
      stunning (ES) vs. gas stunning (GS)] on lipid oxidation in broiler meat and to
      investigate possible mechanisms of lipid oxidation by measuring plasma variables,
      muscle reactive oxygen species (ROS), and TBA reactive substance (TBARS)
      concentrations, muscle fiber ratios, and mRNA levels of avian uncoupling protein
      (avUCP), avian adenine nucleotide translocator, and avian peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (avPGC-1alpha). Arbor Acres broilers
      (n = 36) were not stunned (control) or were exposed to the following stunning
      treatments: 40% CO(2) + 21% O(2) + N(2); 60% CO(2) + 21% O(2) + N(2); 35 V, 47
      mA, 400 Hz; 50 V, 67 mA, 160 Hz; and 65 V, 86 mA, 1,000 Hz. The ROS level in
      tibialis anterior (TA; P < 0.05) and the TBARS concentration in pectoralis major
      (PM; P < 0.01) were decreased in the GS groups compared with the ES groups at 45
      min postmortem. However, the TBARS concentrations at 24 h postmortem in the PM
      and TA groups were not affected by stunning method (ES or GS). Compared with ES,
      GS caused greater expression of avUCP mRNA (1.47-fold in PM, and 2.41-fold in TA)
      and avPGC-1alpha mRNA (1.42-fold in PM, and 2.08-fold in TA). In conclusion, the
      upregulation of avUCP and avPGC-1alpha reduced ROS accumulation and lipid
      oxidation at 45 min postmortem in the skeletal muscles of broilers stunned with
      hypercapnic moderate oxygenation GS. However, these changes were not sufficient
      to cause a difference in meat lipid oxidation at 24 h postmortem between broilers
      stunned with hypercapnic moderate oxygenation GS and those stunned with low
      current, high-frequency ES.

PMID- 21844276
TI  - Gas mixtures approach to improve turkey meat shelf life under modified atmosphere
      packaging: the effect of carbon monoxide.
AB  - Gas mixtures with CO have been applied to beef and pork meat, but no data have
      been reported regarding their application to poultry meat. The aim of this study
      was to evaluate the effect of an anaerobic gas mixture with CO on the growth of
      spoilage flora, color, and lipid oxidation stability of turkey meat under
      modified atmosphere packaging (MAP) stored at 0 degrees C. Sliced meat samples
      were individually packaged under aerobiosis (aerobic packaging) and in 4
      different modified atmospheres containing different gas mixtures: MAP 1, 50% N(2)
      and 50% CO(2); MAP 2, 0.5% CO, 50% CO(2), and 49.5% N(2); MAP 3, 0.5% CO, 80%
      CO(2), and 19.5% N(2); and MAP 4, 100% N(2). All the samples were stored at 0 +/-
      1 degrees C in the dark for 12 to 25 d. Meat samples packaged in aerobic
      packaging were analyzed for their microbial and physicochemical characteristics
      on d 0, 5, and 12 of storage, which was extended to 19 and 25 d when samples were
      under MAP. For meat packaged with MAP 3, the total mesophilic and psychrotrophic
      counts were significantly lower (P < 0.001) than those observed in condition MAP
      1. The introduction of CO, added to a higher concentration of CO(2), inhibited
      microbial flora in general, with particular action on Brochothrix thermosphacta.
      In terms of microbial quality, the shelf life of turkey meat under the MAP study
      conditions was longer than that of meat in aerobic packaging (5 d): 12 d for
      mixture MAP 4, 19 d for MAP 1 and MAP 2, and 25 d for MAP 3. Only MAP 4 without
      CO(2) or CO prevented lipid oxidation of the meat. The presence of CO in anoxic
      gas mixtures with CO(2) for turkey meat under MAP was useful, giving the bright
      pink color preferred by consumers without leading to the appearance of
      undercooked meat.

PMID- 21844277
TI  - Response surface and neural network models for performance of broiler chicks fed
      diets varying in digestible protein and critical amino acids from 11 to 17 days
      of age.
AB  - Central composite design (CCD; 5 levels and 4 factors), response surface
      methodology (RSM), and artificial neural network-genetic algorithm (ANN-GA) were
      used to evaluate the response of broiler chicks [ADG and feed conversion ratio
      (FCR)] to dietary standardized ileal digestible protein (dP), lysine (dLys),
      total sulfur amino acids (dTSAA), and threonine (dThr). A total of 84 battery
      brooder units of 5 birds each were assigned to 28 diets of CCD containing 5
      levels of dP (18-22%), dLys (1.06-1.30%), dTSAA (0.81-1.01%), and dThr (0.66
      0.86%) from 11 to 17 d of age. The experimental results of CCD were fitted with
      the quadratic and artificial neural network models. A ridge analysis (for RSM
      models) and a genetic algorithm (for ANN-GA models) were used to compute the
      optimal response for ADG and FCR. For both ADG and FCR, the goodness of fit in
      terms of R(2) and MS error corresponding to ANN-GA and RSM models showed a
      substantially higher accuracy of prediction for ANN models (ADG model: R(2) =
      0.99; FCR model: R(2) = 0.97) compared with RSM models (ADG model: R(2) = 0.70;
      FCR model: R(2) = 0.71). The ridge maximum analysis on ADG and minimum analysis
      on FCR models revealed that the maximum ADG may be obtained with 18.5, 1.10,
      0.89, and 0.73% dP, dLys, dTSAA, and dThr, respectively, in diet, and minimum FCR
      may be obtained with 19.44, 1.18, 0.90, and 0.75% of dP, dLys, dTSAA, and dThr,
      respectively, in diet. The optimization results of ANN-GA models showed the
      maximum ADG may be achieved with 19.93, 1.06, 0.90, and 0.76% of dP, dLys, dTSAA,
      and dThr, respectively, in diet, and minimum FCR may be achieved with 18.63,
      1.26, 0.84, and 0.69% of dP, dLys, dTSAA, and dThr, respectively, in diet. The
      results of this study revealed that the platform of CCD (for conducting growth
      trials with minimum treatments), RSM model, and ANN-GA (for experimental data
      modeling and optimization) may be used to describe the relationship between
      dietary nutrient concentrations and broiler performance to achieve the optimal
      target.

PMID- 21844278
TI  - Values and public acceptability dimensions of sustainable egg production.
AB  - The attributes of egg production that elicit values-based responses include the
      price and availability of eggs, environmental impacts, food safety or health
      concerns, and animal welfare. Different social groups have distinct interests
      regarding the sustainability of egg production that reflect these diverse values.
      Current scientifically based knowledge about how values and attitudes in these
      groups can be characterized is uneven and must be derived from studies conducted
      at varying times and using incomplete study methods. In general, some producer
      and consumer interests are translated through markets and are mediated by market
      mechanisms, whereas others are poorly reflected by economic behavior. An array of
      survey and focus group research has been performed to elicit consumer and
      activist beliefs about performance goals they would expect from an egg production
      system. These studies provide evidence that consumers' market behavior may be at
      odds with their ethical and political beliefs about performance goals.

PMID- 21844279
TI  - Integration: valuing stakeholder input in setting priorities for socially
      sustainable egg production.
AB  - Setting directions and goals for animal production systems requires the
      integration of information achieved through internal and external processes. The
      importance of stakeholder input in setting goals for sustainable animal
      production systems should not be overlooked by the agricultural animal
      industries. Stakeholders play an integral role in setting the course for many
      aspects of animal production, from influencing consumer preferences to setting
      public policy. The Socially Sustainable Egg Production Project (SSEP) involved
      the development of white papers on various aspects of egg production, followed by
      a stakeholder workshop to help frame the issues for the future of sustainable egg
      production. Representatives from the environmental, food safety, food retail,
      consumer, animal welfare, and the general farm and egg production sectors
      participated with members of the SSEP coordination team in a 1.5-d workshop to
      explore socially sustainable egg production. This paper reviews the published
      literature on values integration methodologies and the lessons learned from
      animal welfare assessment models. The integration method used for the SSEP
      stakeholder workshop and its outcome are then summarized. The method used for the
      SSEP stakeholder workshop can be used to obtain stakeholder input on sustainable
      production in other farm animal industries.

PMID- 21844281
TI  - Transplanted neurally modified bone marrow-derived mesenchymal stem cells promote
      tissue protection and locomotor recovery in spinal cord injured rats.
AB  - BACKGROUND: Stem cell-based therapy for repair and replacement of lost neural
      cells is a promising treatment for central nervous system (CNS) diseases. Bone
      marrow (BM)-derived mesenchymal stem cells (MSCs) can differentiate into neural
      phenotypes and be isolated and expanded for autotransplantation with no risk of
      rejection. OBJECTIVE: The authors examined whether transplanted neurally induced
      human MSCs (NI hMSCs), developed by a new procedure, can survive, differentiate,
      and promote tissue protection and functional recovery in injured spinal cord
      (ISC) rats. METHODS: Neural induction was achieved by exposing cells
      simultaneously to inhibitors of DNA methylation, histone deacetylation, and
      pharmacological agents that increased cAMP levels. Three groups of adult female
      Sprague-Dawley rats were injected immediately rostral and caudal to the midline
      lesion with phosphate-buffered saline, MSCs, or NI hMSCs, 1 week after a spinal
      cord impact injury at T-8. Functional outcome was measured using the Basso
      Beattie Bresnahan (BBB) locomotor rating scale and thermal sensitivity test on a
      weekly basis up to 12 weeks postinjury. Graft integration and anatomy of spinal
      cord was assessed by stereological, histochemical, and immunohistochemical
      techniques. RESULTS: The transplanted NI hMSCs survived, differentiated, and
      significantly improved locomotor recovery of ISC rats. Transplantation also
      reduced the volume of lesion cavity and white matter loss. CONCLUSION: This
      method of hMSC modification may provide an alternative source of autologous adult
      stem cells for CNS repair.

PMID- 21844282
TI  - Effectiveness of intensive inpatient rehabilitation treatment on disease
      progression in parkinsonian patients: a randomized controlled trial with 1-year
      follow-up.
AB  - BACKGROUND: Rehabilitation treatments have acute beneficial effects in
      Parkinson's disease (PD) patients, but whether the effects persist over time is
      unclear. OBJECTIVE: To assess whether an intensive rehabilitation treatment (IRT)
      is effective in improving motor performance compared with a control group in a 12
      month follow-up, to investigate whether a second cycle administered after 1 year
      has the same efficacy as the first treatment, and to determine whether IRT
      reduces the need for increasing levodopa dosage. METHODS: A total of 50 PD
      patients were randomly assigned to 2 groups; 25 participants had 4 weeks of
      inpatient physical therapy that included treadmill and stabilometric platform
      training. At discharge, these patients were invited to continue doing the learned
      exercises. After 12 months, the same treatment was repeated. The control group of
      25 patients received only pharmacological treatment and was invited to practice
      generic physical exercise at home. The rating scales used for the clinical
      evaluation were the Unified Parkinson's Disease Rating Scale Sections II and III
      (UPDRS II and III) and total (UPDRS tot). RESULTS: The authors found that the
      beneficial effects of IRT persisted over time. A second rehabilitation cycle
      administered after 1 year was as effective as the first treatment. At the end of
      the study, daily medication dosage was reduced in treated patients, whereas it
      was significantly increased in control patients. CONCLUSION: These findings
      suggest that the natural worsening of symptoms associated with PD can be
      effectively counteracted by a properly designed IRT.

PMID- 21844283
TI  - Randomized controlled trial of truncal exercises early after stroke to improve
      balance and mobility.
AB  - BACKGROUND: Sitting balance and the ability to perform selective truncal
      movements are important predictors of functional outcome after stroke. However,
      few clinical trials have evaluated the effect of truncal exercises. OBJECTIVE:
      The authors assessed the effect of additional truncal exercises on truncal
      function, standing balance, and mobility. METHODS: An assessor-blinded randomized
      controlled trial was carried out at a stroke rehabilitation hospital. A total of
      33 participants (mean 35 days post onset) were randomly assigned to an
      experimental group (n = 18) or a control group (n = 15). In addition to
      conventional therapy, the experimental group received 16 hours of truncal
      exercises. The control group received 16 hours of sham treatment. Truncal
      function was evaluated by the Trunk Impairment Scale (TIS) and standing balance
      and mobility by the Tinetti Test. The Romberg with eyes open and eyes closed,
      Four Test Balance Scale (FTBS), Berg Balance Scale (BBS), Rivermead Motor
      Assessment Battery (RMAB), Functional Ambulation Categories, and Dynamic Gait
      Index (DGI) were performed to elucidate the findings of the primary outcome
      measures. RESULTS: A treatment effect was found for the experimental group on the
      TIS (P < .001), Tinetti Test (P < .001), FTBS (P = .014), BBS (P = .007), RMAB (P
      < .001), and DGI (P = .006). CONCLUSIONS: In addition to conventional therapy,
      truncal exercises have a beneficial effect on truncal function, standing balance,
      and mobility in people after stroke.

PMID- 21844284
TI  - Beyond the rhetoric of participatory research in indigenous communities: advances
      in Australia over the last decade.
AB  - Evidence-based approaches to health care have been difficult to achieve in
      Indigenous populations across the world, a situation which has contributed to the
      significant health disparities found in this group. One reason for the inadequacy
      of evidence-based health interventions is that empirical knowledge tends to be
      organized around professional disciplines that are grounded in Western ways of
      knowing. In this article we describe events that have led to more appropriate
      research methods in Australia, and the resulting changes in the research
      community. The principles that have guided Australian research policy development
      might not yet be fully matured, but the improvements we have experienced over the
      last several decades have gone a long way toward acknowledging the significant
      disparities that affect Indigenous people and the role of researchers in
      addressing this issue.

PMID- 21844285
TI  - Development of a patient needs assessment model for pulmonary rehabilitation.
AB  - Patients with chronic obstructive pulmonary disease are often referred to
      pulmonary rehabilitation programs to manage their symptoms and the consequences
      of the disease on their lives. Finding ways to target programs to a specific
      patient's needs could help improve individual response to the program. The
      purpose of this study was to develop a conceptual model for the assessment of
      patients' rehabilitation needs by using a grounded theory approach. Focus groups,
      consultations of medical charts, and a literature review helped us develop a
      conceptual model characterized by the following categories: need recognition,
      knowledge, motivation, expectations, goals, ability to fulfill needs, and the
      ability for personal adjustment. Based on a content matrix reflecting the
      conceptual model and disease consequences, items to be included in a prototype
      instrument were formulated and a preliminary validation phase was conducted.

PMID- 21844286
TI  - Overcoming barriers to the recruitment of nurses as participants in health care
      research.
AB  - Adequate participant recruitment is critical for the successful execution of
      research studies involving human subjects. Participant recruitment can be
      particularly challenging when the intended study participants are health care
      providers as opposed to patients. Discussions of the challenges and successful
      strategies associated with provider recruitment are limited, particularly
      regarding providers other than physicians and settings outside of primary care.
      Using a case study format, we present our experiences recruiting inpatient nurses
      into a study which involved focus group methodology at a United States Veterans
      Health Administration facility. We describe the initial logistical and ethical
      issues involved, various challenges we encountered, and five successful action
      strategies used during a second recruitment wave addressing logistical issues; on
      site recruitment; increased scheduling flexibility and peer-to-peer recruitment;
      attention to the sensitive nature of the research topic; and increased
      involvement of stakeholders. In conclusion, we advocate for multimodal
      recruitment strategies that facilitate ongoing investigator-clinician
      partnerships.

PMID- 21844287
TI  - Cross-group friendships and intergroup attitudes: a meta-analytic review.
AB  - This work identifies how cross-group friendships are conceptualized and measured
      in intergroup research, investigates which operationalizations yield the
      strongest effects on intergroup attitudes, explores potential moderators, and
      discusses the theoretical importance of the findings. Prior meta-analyses have
      provided initial evidence that cross-group friendships are especially powerful
      forms of intergroup contact. Although studies of cross-group friendship have
      grown considerably in recent years, varied assessments leave us without a clear
      understanding of how different operationalizations affect relationships between
      friendship and attitudes. With a greatly expanded database of relevant studies,
      the authors compared friendship-attitude associations across a wide range of
      specific conceptualizations. Time spent and self-disclosure with outgroup friends
      yielded significantly greater associations with attitudes than other friendship
      measures, suggesting that attitudes are most likely to improve when cross-group
      friendships involve behavioral engagement. Processes underlying cross-group
      friendships are discussed, as are implications for future research and
      application.

PMID- 21844288
TI  - Neurocognitive outcomes in young adults with early-onset type 1 diabetes: a
      prospective follow-up study.
AB  - OBJECTIVE: The aim of this study was to reexamine the neurocognitive function of
      a cohort of young adults with early-onset type 1 diabetes and compare their
      cognitive function to a matched control group. We also examined whether cognitive
      function was related to prospectively obtained severe hypoglycemia history, long
      term glycemic control, or severe diabetic ketoacidosis. RESEARCH DESIGN AND
      METHODS: Testing included Wechsler Intelligence Scale for Children and Adults,
      Wechsler Memory Scale, Cattell Culture Fair Intelligence Test (CCFIT), Wisconsin
      Card Sorting Test (WCST), youth and adult self-report, and Beck Depression
      Inventory. We tested 34 control subjects (mean +/- SE, age 19.5 +/- 0.5 years)
      and 33 type 1 diabetic subjects (age 19.3 +/- 0.5 years, age at type 1 diabetes
      onset 3.3 +/- 0.3 years, A1C from diagnosis 8.7 +/- 0.1%, and diabetes duration
      16.0 +/- 0.5 years). RESULTS: There was no difference in full-scale IQ scores in
      type 1 diabetic and control subjects (100.7 +/- 2.0 vs. 102.5 +/- 1.4). There was
      no difference between groups in memory subtests or in reporting of emotional and
      behavioral difficulties. The type 1 diabetes group scored lower on the CCFIT for
      fluid intelligence compared with control subjects (P = 0.028) and also scored
      lower on WCST with more perseverative errors (P = 0.002) and fewer categories
      completed (P = 0.022). CONCLUSIONS: These data suggest no difference in general
      intellectual ability, memory, and emotional difficulties in our cohort of young
      adults with early-onset type 1 diabetes compared with control subjects and no
      deterioration over time. There were, however, findings to suggest subtle changes
      leading to poorer performance on complex tasks of executive function.

PMID- 21844290
TI  - Random blood glucose measurement at antenatal booking to screen for overt
      diabetes in pregnancy: a retrospective study.
AB  - OBJECTIVE: To assess random venous blood glucose (RBG) measurement at antenatal
      booking to detect "overt diabetes in pregnancy" (ODIP). RESEARCH DESIGN AND
      METHODS: A retrospective analysis of regional hospital obstetric data from 2004
      2008 was performed. Universal RBG screening was included at booking. Oral glucose
      tolerance test (OGTT) was administered if RBG >7.0 mmol/L or other indications,
      e.g., if a 50-g glucose challenge test was >7.7 mmol/L at 26-28 weeks. ODIP was
      based upon World Health Organization plasma glucose criteria for diabetes.
      RESULTS: RBG data were collected from 17,852/26,369 (67.7%) pregnancies around
      the initial antenatal visit; 3,007 women had an OGTT. The receiver operator curve
      area under the curve for RBG to detect ODIP was 0.86 (0.80-0.92) (assuming women
      without an OGTT did not have ODIP). CONCLUSIONS: RBG at booking may provide a
      sufficiently sensitive screening tool for the detection of ODIP. We recommend
      further studies and comparison with fasting glucose and HbA(1c).

PMID- 21844289
TI  - Impact of subclinical atherosclerosis on cardiovascular disease events in
      individuals with metabolic syndrome and diabetes: the multi-ethnic study of
      atherosclerosis.
AB  - OBJECTIVE: While metabolic syndrome (MetS) and diabetes confer greater
      cardiovascular disease (CVD) risk, recent evidence suggests that individuals with
      these conditions have a wide range of risk. We evaluated whether screening for
      coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can
      improve CVD risk stratification over traditional risk factors (RFs) in people
      with MetS and diabetes. RESEARCH DESIGN AND METHODS: We assessed CAC and CIMT in
      6,603 people aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis
      (MESA). Cox regression examined the association of CAC and CIMT with coronary
      heart disease (CHD) and CVD over 6.4 years in MetS and diabetes. RESULTS: Of the
      subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual
      CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF
      adjusted hazard ratios for CHD for CAC 1-99 to >=400 vs. 0 in subjects with
      neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged
      from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P
      < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C
      statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added
      negligibly to prediction over RFs. CONCLUSIONS: Individuals with MetS or diabetes
      have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and
      CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can
      stratify risk in people with MetS and diabetes and support the latest
      recommendations regarding CAC screening in those with diabetes.

PMID- 21844295
TI  - Nifedipine affects the course of Salmonella enterica serovar Typhimurium
      infection by modulating macrophage iron homeostasis.
AB  - BACKGROUND: Iron overload can adversely influence the course of infection by
      increasing microbial replication and suppressing antimicrobial immune effector
      pathways. Recently, we have shown that the calcium channel blocker nifedipine can
      mobilize tissue iron in mouse models of iron overload. We therefore investigated
      whether nifedipine treatment affects the course of infection with intracellular
      bacteria via modulation of iron homeostasis. METHODS: The effect of nifedipine on
      intramacrophage replication of bacteria and modulation of cellular iron
      homeostasis was investigated in the murine macrophage cell line RAW264.7, and the
      impact of nifedipine treatment on the course of systemic infection was
      investigated in C57BL/6 mice in vivo. RESULTS: In RAW264.7 cells, nifedipine
      treatment significantly reduced intracellular bacterial survival of Salmonella
      enterica serovar Typhimurium and Chlamydophila pneumoniae. This could be
      attributed to the induction of the iron exporter ferroportin 1, which limited the
      availability of iron for intracellular Salmonella. When C57BL/6 mice were
      infected intraperitoneally with Salmonella and subsequently injected with
      nifedipine for 3 consecutive days, bacterial counts in livers and spleens were
      significantly reduced and survival of the mice significantly was prolonged
      compared with solvent-treated littermates. Nifedipine treatment increased
      expression of ferroportin 1 in the spleen, whereas splenic levels of the iron
      storage protein ferritin and serum iron concentrations were reduced. CONCLUSIONS:
      Our data provide evidence for a novel mechanism whereby nifedipine enhances host
      resistance to intracellular pathogens via limitation of iron availability.

PMID- 21844297
TI  - Adhesin and superantigen genes and the capacity of Staphylococcus aureus to
      colonize the infantile gut.
AB  - Staphylococcus aureus is a pathogen and a skin commensal that is today also
      common in the infant gut flora. We examine the role of S. aureus virulence
      factors for gut colonization. S. aureus isolated from quantitative stool cultures
      of 49 Swedish infants followed from birth to 12 months of age were assessed for
      30 virulence-associated genes, spa type, and agr allele by serial polymerase
      chain reaction (PCR) assays. Strains carrying genes encoding collagen-binding
      protein, and the superantigens S. aureus enterotoxin O/M (SEO/SEM) had higher
      stool counts than strains lacking these genes, whereas genes for S. aureus
      enterotoxin A (SEA) were associated with low counts. A cluster of strains
      belonging to agr allele I and the spa clonal cluster 630 (spa-CC 630) that
      carried genes encoding SEO/SEM, SEC, collagen-binding protein, and elastin
      binding protein were all long-time colonizers. Thus, certain S. aureus virulence
      factors might promote gut colonization.

PMID- 21844298
TI  - S100A4 deficiency is associated with efficient bacterial clearance and protects
      against joint destruction during Staphylococcal infection.
AB  - BACKGROUND: Efficient host defense mechanisms are crucial for survival in sepsis
      and septic arthritis. S100 proteins are reported to have proinflammatory and
      bactericidal properties. The aim of this study was to investigate the role of
      S100A4 in staphylococcal arthritis. METHODS: S100A4 knockout mice (S100A4KO) and
      wild-type counterparts (WT) were intravenously and intra-articularly challenged
      with Staphylococcus aureus strain LS-1. Clinical and morphological signs of
      arthritis and sepsis, phagocytosis, bone mineral density (BMD), and bone
      metabolism were then monitored in S100A4 and WT mice. RESULTS: S100A4KO mice had
      a lower bacterial load in the kidneys than WT mice (P < .05) but developed more
      severe clinical signs of arthritis (P < .001) and had higher levels of
      interleukin 6 and L-selectin (P = .002). S100A4KO mice had fewer morphological
      signs of synovitis and cartilage/bone destruction following intra-articular
      instillation of bacteria. S100A4KO mice were protected from loss of BMD and had
      lower levels of RANKL, MMP3, and MMP9 (P < .05). S100A4 was not bactericidal in
      vitro. CONCLUSIONS: In staphylococcal infection, S100A4 regulates bacterial
      clearance as well as systemic and local inflammatory responses.

PMID- 21844296
TI  - Methicillin-susceptible Staphylococcus aureus endocarditis isolates are
      associated with clonal complex 30 genotype and a distinct repertoire of
      enterotoxins and adhesins.
AB  - BACKGROUND: Using multinational collections of methicillin-susceptible
      Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft
      tissue infections (STIs), we sought to (1) validate the finding that S. aureus in
      clonal complex (CC) 30 is associated with hematogenous complications and (2) test
      the hypothesis that specific genetic characteristics in S. aureus are associated
      with infection severity. METHODS: IE and STI isolates from 2 cohorts were
      frequency matched by geographic origin. Isolates underwent spa typing to infer CC
      and multiplex polymerase chain reaction for presence of virulence genes. RESULTS:
      114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5%
      vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for
      all) and 5 enterotoxins (tst, sea, sed, see, and sei; P <= .005 for all). CC30
      isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05
      for all). CONCLUSIONS: MSSA IE isolates were significantly more likely to be CC30
      and to possess a distinct repertoire of virulence genes than MSSA STI isolates
      from the same region. The genetic basis of this association requires further
      study.

PMID- 21844299
TI  - OatA, a peptidoglycan O-acetyltransferase involved in Listeria monocytogenes
      immune escape, is critical for virulence.
AB  - Microbial pathogens have evolved mechanisms to overcome immune responses and
      successfully infect their host. Here, we studied how Listeria monocytogenes
      evades immune detection by peptidoglycan (PGN) modification. By analyzing L.
      monocytogenes muropeptides, we detected O-acetylated muramic acid residues. We
      identified an O-acetyltransferase gene, oatA, in the L. monocytogenes genome
      sequence. Comparison of PGN from parental and isogenic oatA mutant strains showed
      that the O-acetyltransferase OatA O-acetylates Listeria PGN. We also found that
      PGN O-acetylation confers resistance to different types of antimicrobial
      compounds targeting bacterial cell wall such as lysozyme, beta-lactam
      antibiotics, and bacteriocins and that O-acetylation is required for Listeria
      growth in macrophages. Moreover, oatA mutant virulence is drastically affected in
      mice following intravenous or oral inoculation. In addition, the oatA mutant
      induced early secretion of proinflammatory cytokines and chemokines in vivo.
      These results suggest an important role for OatA in limiting innate immune
      responses and promoting bacterial survival in the infected host.

PMID- 21844302
TI  - HIV-1 RNA rectal shedding is reduced in men with low plasma HIV-1 RNA viral loads
      and is not enhanced by sexually transmitted bacterial infections of the rectum.
AB  - BACKGROUND: Among human immunodeficiency virus (HIV)-infected men who have sex
      with men (MSM) taking combination antiretroviral therapy (cART), the impact of
      rectal sexually transmitted infections (STIs) on rectal HIV-1 shedding is
      unknown. METHODS: Human immunodeficiency virus type 1 (HIV-1) RNA was quantified
      from rectal swabs collected for Neisseria gonorrhoeae (GC) and Chlamydia
      trachomatis (CT) screening of HIV-1-infected MSM. Correlations of STIs with
      rectal viral load were explored using multinomial regression modeling. HIV-1
      coreceptor tropism was predicted from sequencing in a subset of men. RESULTS:
      Thirty-one (39%) of 80 men (59 prescribed combination antiretroviral therapy
      [cART]) had HIV detected in 38 (42%) of 91 rectal swabs. Rectal HIV detection was
      associated with plasma virus loads above 3.15 log10 copies/mL (95% confidence
      limit [CL] 2.73, 3.55) and paired rectal viral loads and plasma viral loads were
      correlated (Kendall's tau [tau] 0.68, Spearman rho [P] = .77). Rectal STIs and
      abnormal anal cytology were not associated with rectal viral load. HIV coreceptor
      distribution was very similar between the plasma and rectum in 3 of 4 men.
      CONCLUSIONS: Plasma and rectal viral load were correlated, and rectal STIs did
      not increase the likelihood of detecting HIV in the rectal secretions in MSM,
      including those with low or undetectable plasma viral load. Suppressing plasma
      viral load is likely to reduce risk of HIV transmission to insertive partners.

PMID- 21844301
TI  - Central nervous system immune activation characterizes primary human
      immunodeficiency virus 1 infection even in participants with minimal
      cerebrospinal fluid viral burden.
AB  - BACKGROUND: Central nervous system (CNS) human immunodeficiency virus (HIV)
      infection and immune activation lead to brain injury and neurological impairment.
      Although HIV enters the nervous system soon after transmission, the magnitude of
      infection and immunoactivation within the CNS during primary HIV infection (PHI)
      has not been characterized. METHODS: This cross-sectional study analyzed
      cerebrospinal fluid (CSF) and blood from 96 participants with PHI and compared
      them with samples from neuroasymptomatic participants with chronic infection and
      >= 200 or < 200 blood CD4 T cells/MUL, and with samples from HIV-seronegative
      participants with respect to CSF and plasma HIV RNA, CSF to serum albumin ratio,
      and CSF white blood cell counts (WBC), neopterin levels, and concentrations of
      chemokines CXCL10 and CCL2. RESULTS: The PHI participants (median 77 days post
      transmission) had CSF HIV RNA, WBC, neopterin, and CXCL10 concentrations similar
      to the chronic infection participants but uniquely high albumin ratios. 18
      participants had <= 100 copies/mL CSF HIV RNA, which was associated with low CSF
      to plasma HIV ratios and levels of CSF inflammation lower than in other PHI
      participants but higher than in HIV-seronegative controls. CONCLUSIONS: Prominent
      CNS infection and immune activation is evident during the first months after HIV
      transmission, though a proportion of PHI patients demonstrate relatively reduced
      CSF HIV RNA and inflammation during this early period.

PMID- 21844300
TI  - A376S in the connection subdomain of HIV-1 reverse transcriptase confers
      increased risk of virological failure to nevirapine therapy.
AB  - BACKGROUND: The clinical relevance of mutations in the connection subdomain and
      the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is
      uncertain. METHODS: The risk of virological failure to nonnucleoside RT inhibitor
      (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients
      who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting
      substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An
      observed association between A376S and virological failure was further
      investigated by testing in vitro NNRTI susceptibility of single site-directed
      mutants and patient-derived recombinant viruses. Enzymatic assays also determined
      the effects of A376S on nevirapine and template-primer binding to HIV-1 RT.
      RESULTS: Virological failure occurred in 142 of 287 (49%) individuals: 77
      receiving nevirapine (67%) and 65 receiving efavirenz (38%) (P < .001).
      Preexisting A376S was associated with an increased risk of virological failure to
      nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7),
      but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2)
      (P value for interaction = .013). A376S conferred selective low-level nevirapine
      resistance in vitro, and led to greater affinity for double-stranded DNA.
      CONCLUSIONS: The A376S substitution in the connection subdomain of HIV-1 RT
      causes selective nevirapine resistance and confers an increased risk of
      virological failure to nevirapine-based ART.

PMID- 21844303
TI  - Limited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus
      infection.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) responses
      contribute to the decline in acute peak viremia following infection. However,
      data on the relative immunogenicity of CD8(+) T-cell epitopes during and after
      acute viremia are lacking. METHODS: We characterized CD8(+) T-cell responses in
      20 acutely infected, antiretroviral-naive individuals with HIV-1 subtype C
      infection using the interferon-gamma enzyme-linked immunosorbent spot assay.
      Eleven of these had not fully seroconverted at the time of analysis. Viruses from
      plasma were sequenced within defined cytotoxic T-lymphocyte (CTL) cell epitopes
      for selected subjects. RESULTS: At approximately 28 days after estimated initial
      infection, CD8(+) T-cell responses were directed against an average of 3 of the
      410 peptides tested (range, 0-6); 2 individuals had no detectable responses at
      this time. At 18 weeks, the average number of peptides targeted had increased to
      5 (range 0-11). Of the 56 optimal Gag CTL epitopes sequenced, 31 were wild-type
      in the infecting viruses, but only 11 of 31 elicited measurable CD8(+) T-cell
      responses. CONCLUSIONS: These data demonstrate that the majority of CD8(+)
      responses are not elicited during acute HIV infection despite the presence of the
      cognate epitope in the infecting strain. There is a need to define factors that
      influence lack of induction of effective immune responses and the parameters that
      dictate immunodominance in acute infection.

PMID- 21844304
TI  - Evaluation of the antiviral response to zanamivir administered intravenously for
      treatment of critically ill patients with pandemic influenza A (H1N1) infection.
AB  - A retrospective nationwide study on the use of intravenous (IV) zanamivir in
      patients receiving intensive care who were pretreated with oseltamivir in the
      Netherlands was performed. In 6 of 13 patients with a sustained reduction of the
      viral load, the median time to start IV zanamivir was 9 days (range, 4-11 days)
      compared with 14 days (range, 6-21 days) in 7 patients without viral load
      reduction (P = .052). Viral load response did not influence mortality. We
      conclude that IV zanamivir as late add-on therapy has limited effectiveness. The
      effect of an immediate start with IV zanamivir monotherapy or in combination with
      other drugs need to be evaluated.

PMID- 21844306
TI  - Hepatitis C Virus nonstructural 5A protein inhibits lipopolysaccharide-mediated
      apoptosis of hepatocytes by decreasing expression of Toll-like receptor 4.
AB  - BACKGROUND: Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) has been
      shown to modulate multiple cellular processes, including apoptosis. The aim of
      this study was to assess the effects of HCV NS5A on apoptosis induced by Toll
      like receptor (TLR) 4 ligand, lipopolysaccharide (LPS). METHODS: Apoptotic
      responses to TLR4 ligands and the expression of molecules involved in TLR
      signaling pathways in human hepatocytes were examined with or without expression
      of HCV NS5A. RESULTS: HCV NS5A protected HepG2 hepatocytes against LPS-induced
      apoptosis, an effect linked to reduced TLR4 expression. A similar downregulation
      of TLR4 expression was observed in Huh-7-expressing genotype 1b and 2a. In
      agreement with these findings, NS5A inhibited the expression of numerous genes
      encoding for molecules involved in TLR4 signaling, such as CD14, MD-2, myeloid
      differentiation primary response gene 88, interferon regulatory factor 3, and
      nuclear factor-kappaB2. Consistent with a conferred prosurvival advantage, NS5A
      diminished the poly(adenosine diphosphate-ribose) polymerase cleavage and the
      activation of caspases 3, 7, 8, and 9 and increased the expression of anti
      apoptotic molecules Bcl-2 and c-FLIP. CONCLUSIONS: HCV NS5A downregulates TLR4
      signaling and LPS-induced apoptotic pathways in human hepatocytes, suggesting
      that disruption of TLR4-mediated apoptosis may play a role in the pathogenesis of
      HCV infection.

PMID- 21844305
TI  - The oral cavity contains abundant known and novel human papillomaviruses from the
      Betapapillomavirus and Gammapapillomavirus genera.
AB  - BACKGROUND: Human papillomaviruses (HPVs) primarily sort into 3 genera:
      Alphapapillomavirus (alpha-HPV), predominantly isolated from mucosa, and
      Betapapillomavirus (beta-HPV) and Gammapapillomavirus (gamma-HPV), predominantly
      isolated from skin. HPV types might infect body sites that are different from
      those from which they were originally isolated. METHODS: We investigated the
      spectrum of HPV type distribution in oral rinse samples from 2 populations: 52
      human immunodeficiency virus (HIV)-positive men and women and 317 men who
      provided a sample for genomic DNA for a prostate cancer study. HPV types were
      detected with the MY09/MY11 and FAP59/64 primer systems and identified by dot
      blot hybridization and/or direct sequencing. RESULTS: Oral rinse specimens from
      35 (67%) of 52 HIV-positive individuals and 117 (37%) of 317 older male
      participants tested positive for HPV DNA. We found 117 type-specific HPV
      infections from the HIV-positive individuals, including 73 alpha-HPV, 33 beta
      HPV, and 11 gamma-HPV infections; whereas, the distribution was 46 alpha-HPV, 108
      beta-HPV, and 14 gamma-HPV infections from 168 type-specific infections from the
      317 male participants. CONCLUSIONS: The oral cavity contains a wide spectrum of
      HPV types predominantly from the beta-HPV and gamma-HPV genera, which were
      previously considered to be cutaneous types. These results could have significant
      implications for understanding the biology of HPV and the epidemiological
      associations of HPV with oral and skin neoplasia.

PMID- 21844307
TI  - Candida albicans Hgt1p, a multifunctional evasion molecule: complement inhibitor,
      CR3 analogue, and human immunodeficiency virus-binding molecule.
AB  - BACKGROUND: The complement system is tightly controlled by several regulators.
      Two of these, factor H (FH) and C4b-binding protein (C4BP), can be acquired by
      pathogens conveying resistance to complement attack. The aim of the study was to
      characterize the FH binding molecule of Candida albicans, a potentially life
      threatening yeast. METHODS: The gene coding for this molecule was identified by
      probing an expression library and homozygous deletion mutants of the respective
      gene were constructed. Binding and functional assays were undertaken to compare
      wild-type and knockout strains. RESULTS: The high-affinity glucose transporter 1
      (CaHgt1p) was identified as an FH-binding molecule. Homozygous hgt1Delta/Delta
      deletion mutants, but not the restored strain in which HGT1 was reintegrated,
      showed a decreased binding of FH and even of C4BP, demonstrating its function as
      an FH- and C4BP-binding protein. This led to an enhanced terminal complement
      complex deposition after incubation with human serum; CaHgt1p thus functions as
      complement inhibitor. hgt1Delta/Delta mutants failed to form rosettes with
      complement-coated sheep erythrocytes, and show reduced binding to HIV-gp160,
      implying that a complement receptor 3 (CR3) moiety, known as fungal HIV binding
      molecule is lacking. CONCLUSIONS: CaHgt1p is a multifunctional evasion molecule,
      as complement inhibitor, CR3 analogue and HIV receptor.

PMID- 21844308
TI  - Strengthening observational evidence for antiviral effectiveness in influenza A
      (H5N1).

PMID- 21844309
TI  - The rice miniature inverted repeat transposable element mPing is an effective
      insertional mutagen in soybean.
AB  - Insertional mutagenesis of legume genomes such as soybean (Glycine max) should
      aid in identifying genes responsible for key traits such as nitrogen fixation and
      seed quality. The relatively low throughput of soybean transformation
      necessitates the use of a transposon-tagging strategy where a single
      transformation event will produce many mutations over a number of generations.
      However, existing transposon-tagging tools being used in legumes are of limited
      utility because of restricted transposition (Ac/Ds: soybean) or the requirement
      for tissue culture activation (Tnt1: Medicago truncatula). A recently discovered
      transposable element from rice (Oryza sativa), mPing, and the genes required for
      its mobilization, were transferred to soybean to determine if it will be an
      improvement over the other available transposon-tagging tools. Stable
      transformation events in soybean were tested for mPing transposition. Analysis of
      mPing excision at early and late embryo developmental stages revealed increased
      excision during late development in most transgenic lines, suggesting that
      transposition is developmentally regulated. Transgenic lines that produced
      heritable mPing insertions were identified, with the plants from the highest
      activity line producing at least one new insertion per generation. Analysis of
      the mPing insertion sites in the soybean genome revealed that features displayed
      in rice were retained including transposition to unlinked sites and a preference
      for insertion within 2.5 kb of a gene. Taken together these findings indicate
      that mPing has the characteristics necessary for an effective transposon-tagging
      resource.

PMID- 21844311
TI  - Citrobacter spp. as a source of qnrB Alleles.
AB  - qnrB is the most common of the five qnr families and has the greatest number of
      allelic variants. Almost two-thirds of the qnrB alleles have been reported in
      Citrobacter spp., and several were shown to be located on the chromosome. In this
      study, PCR was used to investigate the prevalence of plasmid-mediated quinolone
      resistance genes in 71 clinical isolates belonging to the Citrobacter freundii
      complex. Thirty-seven percent contained qnrB alleles, including 7 (qnrB32 to
      qnrB38) that were novel and 1 pseudogene, while none contained qnrA, qnrC, qnrD,
      qnrS, or aac(6')-Ib-cr. When the strains were arrayed by related 16S rRNA
      sequence and further separated into subspecies by biochemical criteria,
      clustering of qnrB-positive strains was evident. In only two strains with qnrB2
      and qnrB4 was quinolone resistance transferable by conjugation, and only these
      strains contained the ISCR1 sequence that is often associated with qnrB on
      plasmids. Five of 26 qnrB-positive strains contained integrase genes, but these
      included the strains with qnrB2 and qnrB4 as well as two strains with other
      transmissible plasmids. In a fully sequenced genome of Citrobacter youngae, a
      member of the C. freundii complex, another novel qnrB allele, qnrB39, occurs in a
      sequence of genes that is 90% identical to sequence surrounding integron
      associated qnrB4 incorporated into plasmids. The chromosome of Citrobacter is the
      likely source of plasmid-mediated qnrB.

PMID- 21844312
TI  - In vitro activity of a novel broad-spectrum antifungal, E1210, tested against
      Aspergillus spp. determined by CLSI and EUCAST broth microdilution methods.
AB  - E1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth
      by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present
      study, we extend these findings by examining the activity of E1210 and comparator
      antifungal agents against Aspergillus spp. by using the methods of the Clinical
      and Laboratory Standards Institute (CLSI) and the European Committee for
      Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as
      amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI
      methods). Seventy-eight clinical isolates of Aspergillus were tested including 20
      isolates of Aspergillus flavus species complex (SC), 22 of A. fumigatus SC, 13 of
      A. niger SC, and 23 of A. terreus SC. The collection included 15 AMB-R (MIC, >= 2
      MUg/ml) isolates of A. terreus SC and 10 itraconazole-R (MIC, >= 4 MUg/ml)
      isolates of A. fumigatus SC (7 isolates), A. niger SC (2 isolates), and A.
      terreus SC (1 isolate). Comparator antifungal agents included anidulafungin,
      caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both
      CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The
      essential agreement (EA; +/- 2 log(2) dilution steps) was 100% for all
      comparisons with the exception of posaconazole versus A. terreus SC (EA = 91.3%).
      The minimum effective concentration (MEC)/MIC(90) values (MUg/ml) for E1210,
      anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole,
      respectively, were as follows for each species: for A. flavus SC, 0.03, <= 0.008,
      0.12, 1, 1, and 1; for A. fumigatus SC, 0.06, 0.015, 0.12, >8, 1, and 4; for A.
      niger SC, 0.015, 0.03, 0.12, 4, 1, and 2; and for A. terreus SC, 0.06, 0.015,
      0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains of A. terreus SC
      (MEC range, 0.015 to 0.06 MUg/ml) and itraconazole-R strains of A. fumigatus SC
      (MEC range, 0.03 to 0.12 MUg/ml), A. niger SC (MEC, 0.008 MUg/ml), and A. terreus
      SC (MEC, 0.015 MUg/ml). In conclusion, E1210 was a very potent and broad-spectrum
      antifungal agent regardless of in vitro method applied, with excellent activity
      against AMB-R and itraconazole-R strains of Aspergillus spp.

PMID- 21844310
TI  - The Arabidopsis bZIP gene AtbZIP63 is a sensitive integrator of transient
      abscisic acid and glucose signals.
AB  - Glucose modulates plant metabolism, growth, and development. In Arabidopsis
      (Arabidopsis thaliana), Hexokinase1 (HXK1) is a glucose sensor that may trigger
      abscisic acid (ABA) synthesis and sensitivity to mediate glucose-induced
      inhibition of seedling development. Here, we show that the intensity of short
      term responses to glucose can vary with ABA activity. We report that the
      transient (2 h/4 h) repression by 2% glucose of AtbZIP63, a gene encoding a basic
      leucine zipper (bZIP) transcription factor partially involved in the Snf1-related
      kinase KIN10-induced responses to energy limitation, is independent of HXK1 and
      is not mediated by changes in ABA levels. However, high-concentration (6%)
      glucose-mediated repression appears to be modulated by ABA, since full repression
      of AtbZIP63 requires a functional ABA biosynthetic pathway. Furthermore, the
      combination of glucose and ABA was able to trigger a synergistic repression of
      AtbZIP63 and its homologue AtbZIP3, revealing a shared regulatory feature
      consisting of the modulation of glucose sensitivity by ABA. The synergistic
      regulation of AtbZIP63 was not reproduced by an AtbZIP63 promoter-5'-untranslated
      region::beta-glucuronidase fusion, thus suggesting possible posttranscriptional
      control. A transcriptional inhibition assay with cordycepin provided further
      evidence for the regulation of mRNA decay in response to glucose plus ABA.
      Overall, these results indicate that AtbZIP63 is an important node of the glucose
      ABA interaction network. The mechanisms by which AtbZIP63 may participate in the
      fine-tuning of ABA-mediated abiotic stress responses according to sugar
      availability (i.e., energy status) are discussed.

PMID- 21844314
TI  - Efficacy of human-simulated exposures of tomopenem (formerly CS-023) in a murine
      model of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus
      infection.
AB  - Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against
      diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin
      resistant Staphylococcus aureus (MRSA), and has a half-life about twice longer
      than the half-lives of other carbapenems such as imipenem and meropenem. Our
      objective in this study was to estimate the efficacy of tomopenem in humans by
      human-simulated exposures in a neutropenic murine thigh infection model against 9
      clinical isolates of P. aeruginosa with MICs of 4 to 32 MUg/ml and 9 clinical
      isolates of MRSA with MICs of 4 to 16 MUg/ml. Human-simulated dosing regimens in
      neutropenic mice were designed to approximate the cumulative percentage of a 24-h
      period that the free drug concentration exceeds the MIC under steady-state
      pharmacokinetic conditions (f%T(MIC)) observed with tomopenem at 750 and 1,500 mg
      given as a 0.5-h infusion three times a day (TID) in humans. As reported
      previously, there was no difference between the target values of P. aeruginosa
      and MRSA required for efficacy (K. Sugihara et al., Antimicrob. Agents Chemother.
      54:5298-5302, 2010). Tomopenem at 750 mg showed bactericidal or bacteriostatic
      effects against 10 of 11 strains of P. aeruginosa and MRSA with MICs of <= 8
      MUg/ml (f%T(MIC) >= 41), and tomopenem at 1,500 mg showed bactericidal effects
      against 16 of 17 strains of P. aeruginosa and MRSA with MICs of <= 16 MUg/ml
      (f%T(MIC) >= 43). Meropenem at 1,000 mg TID was tested for comparison purposes
      and showed bactericidal or bacteriostatic effects against 3 of 4 strains of P.
      aeruginosa with MICs of <= 4 MUg/ml (f%T(MIC) >= 33). From these results,
      tomopenem is expected to be effective with an f%T(MIC) of over 40 against P.
      aeruginosa and MRSA strains with MICs of <= 8 MUg/ml at doses of 750 mg TID and
      strains with MICs of <= 16 MUg/ml at doses of 1,500 mg TID.

PMID- 21844313
TI  - Antibacterial mechanism of action of arylamide foldamers.
AB  - Small arylamide foldamers designed to mimic the amphiphilic nature of
      antimicrobial peptides (AMPs) have shown potent bactericidal activity against
      both Gram-negative and Gram-positive strains without many of the drawbacks of
      natural AMPs. These foldamers were shown to cause large changes in the
      permeability of the outer membrane of Escherichia coli. They cause more limited
      permeabilization of the inner membrane which reaches critical levels
      corresponding with the time required to bring about bacterial cell death.
      Transcriptional profiling of E. coli treated with sublethal concentrations of the
      arylamides showed induction of genes related to membrane and oxidative stresses,
      with some overlap with the effects observed for polymyxin B. Protein secretion
      into the periplasm and the outer membrane is also compromised, possibly
      contributing to the lethality of the arylamide compounds. The induction of
      membrane stress response regulons such as rcs coupled with morphological changes
      at the membrane observed by electron microscopy suggests that the activity of the
      arylamides at the membrane represents a significant contribution to their
      mechanism of action.

PMID- 21844315
TI  - Wide dissemination of Pseudomonas aeruginosa producing beta-lactamase blaKPC-2
      gene in Colombia.
AB  - Ten bla(KPC-2)-harboring Pseudomonas aeruginosa isolates from hospitals located
      in five different Colombian cities have been characterized. Isolates were
      multidrug resistant, belonged to five different pulsotypes, and possessed
      naturally chromosome-encoded bla(AmpC) and bla(OXA-50) genes and the acquired
      bla(KPC-2) gene. In most cases, the bla(KPC-2) genes were carried by plasmids of
      different sizes and were associated with Tn4401b or a new structure containing
      only part of the Tn4401 sequence. This study revealed that several clones of P.
      aeruginosa producing bla(KPC-2) are disseminating in Colombia.

PMID- 21844316
TI  - A novel target-specific, salt-resistant antimicrobial peptide against the
      cariogenic pathogen Streptococcus mutans.
AB  - In this study, we constructed and evaluated a target-specific, salt-resistant
      antimicrobial peptide (AMP) that selectively targeted Streptococcus mutans, a
      leading cariogenic pathogen. The rationale for creating such a peptide was based
      on the addition of a targeting domain of S. mutans ComC signaling peptide
      pheromone (CSP) to a killing domain consisting of a portion of the marine
      derived, broad-spectrum AMP pleurocidin to generate a target-specific AMP. Here,
      we report the results of our assessment of such fusion peptides against S. mutans
      and two closely related species. The results showed that nearly 95% of S. mutans
      cells lost viability following exposure to fusion peptide IMB-2 (5.65 MUM) for 15
      min. In contrast, only 20% of S. sanguinis or S. gordonii cells were killed
      following the same exposure. Similar results were also observed in dual-species
      mixed cultures of S. mutans with S. sanguinis or S. gordonii. The peptide-guided
      killing was further confirmed in S. mutans biofilms and was shown to be dose
      dependent. An S. mutans mutant defective in the CSP receptor retained 60%
      survival following exposure to IMB-2, suggesting that the targeted peptide
      predominantly bound to the CSP receptor to mediate killing in the wild-type
      strain. Our work confirmed that IMB-2 retained its activity in the presence of
      physiological or higher salt concentrations. In particular, the fusion peptide
      showed a synergistic killing effect on S. mutans with a preventive dose of NaF.
      In addition, IMB-2 was relatively stable in the presence of saliva containing 1
      mM EDTA and did not cause any hemolysis. We also found that replacement of serine
      14 by histidine improved its activity at lower pH. Because of its effectiveness,
      salt resistance, and minimal toxicity to host cells, this novel target-specific
      peptide shows promise for future development as an anticaries agent.

PMID- 21844317
TI  - Efficacy of single intravenous injection of peramivir against influenza B virus
      infection in ferrets and cynomolgus macaques.
AB  - We evaluated the efficacy of a single intravenous dose peramivir for treatment of
      influenza B virus infection in ferrets and cynomolgus macaques in the present
      study. A single dose of peramivir (60 mg/kg of body weight) given to ferrets on 1
      day postinfection with influenza B virus significantly reduced median area under
      the curve (AUC) virus titers (peramivir, 8.3 log(10) 50% tissue culture infective
      doses [TCID(50)s] . day/ml; control, 10.7 log(10) TCID(50)s . day/ml; P <
      0.0001). Furthermore, nasal virus titers on day 2 postinfection in ferrets
      receiving a single injection of peramivir (30 mg/kg) and AUCs of the body
      temperature increase in ferrets receiving a single injection of peramivir (30 and
      60 mg/kg) were lower than those in ferrets administered oral oseltamivir
      phosphate (30 and 60 mg/kg/day twice daily for 3 days). In macaques infected with
      influenza B virus, viral titers in the nasal swab fluid on days 2 and 3
      postinfection and body temperature after a single injection of peramivir (30
      mg/kg) were lower than those after oral administration of oseltamivir phosphate
      (30 mg/kg/day for 5 days). The two animal models used in the present study
      demonstrated that inhibition of viral replication at the early time point after
      infection was critical in reduction of AUCs of virus titers and interleukin-6
      production, resulting in amelioration of symptoms. Our results shown in animal
      models suggest that the early treatment with a single intravenous injection of
      peramivir is clinically recommended to reduce symptoms effectively in influenza B
      virus infection.

PMID- 21844318
TI  - Comparative susceptibilities to fidaxomicin (OPT-80) of isolates collected at
      baseline, recurrence, and failure from patients in two phase III trials of
      fidaxomicin against Clostridium difficile infection.
AB  - A 10-day course of oral fidaxomicin (200 mg twice a day [b.i.d.]), a potent new
      macrocyclic drug, was compared to vancomycin (125 mg four times a day [q.i.d.])
      in 1,164 adults (1,105 in the modified intent-to-treat [mITT] population) with
      Clostridium difficile infection in two phase III randomized, double-blind trials
      at sites in North America and 7 European countries. Of 1,105 mITT patients, 792
      (71.7%), including 719/999 (72.0%) in the per-protocol (PP) population, provided
      a C. difficile strain at baseline, of whom 356 received fidaxomicin with 330
      cures (92.7%) and 363 received vancomycin with 329 cures (90.6%). The
      susceptibilities (MIC(90)) of baseline isolates did not predict clinical cure,
      failure, or recurrence for fidaxomicin (MIC(90), 0.25 MUg/ml for both; range, <=
      0.007 to 1 MUg/ml), but there was a one-dilution difference in the MIC(90) (but
      not the MIC(50)) for vancomycin (MIC(90), 2 MUg/ml [range, 0.25 to 8 MUg/ml] for
      cure and 4.0 MUg/ml [range, 0.5 to 4 MUg/ml] for failures). A total of 65 (7.9%)
      "rifaximin-resistant" (MIC > 256 MUg/ml) strains were isolated in both treatment
      groups on enrollment, which increased to 25% for failures at the end of therapy.
      No resistance to either fidaxomicin or vancomycin developed during treatment in
      either of the phase III studies, although a single strain isolated from a cured
      patient had an elevated fidaxomicin MIC of 16 MUg/ml at the time of recurrence.
      All isolates were susceptible to <= 4 MUg/ml of metronidazole. When analyzed by
      restriction endonuclease analysis (REA) type, 247/719 (34.4%) isolates were BI
      group isolates, and the MICs were generally higher for all four drugs tested
      (MIC(90)s: fidaxomicin, 0.5; vancomycin, 2.0; metronidazole, 2.0; and rifaximin,
      >256 MUg/ml) than for the other REA types. There was no correlation between the
      MIC of a baseline clinical isolate and clinical outcome. MIC(90)s were generally
      low for fidaxomicin and vancomycin, but BI isolates had higher MICs than other
      REA group isolates.

PMID- 21844319
TI  - Enhancement of vancomycin activity against biofilms by using ultrasound-targeted
      microbubble destruction.
AB  - Treating biofilm infections on implanted medical devices is formidable, even with
      extensive antibiotic therapy. The aim of this study was to investigate whether
      ultrasound (US)-targeted microbubble (MB) destruction (UTMD) could enhance
      vancomycin activity against Staphylococcus epidermidis RP62A biofilms. Twelve
      hour biofilms were treated with vancomycin combined with UTMD. The vancomycin and
      MB (SonoVue) were used at concentrations of 100 MUg/ml and 30% (vol/vol),
      respectively, in studies in vitro. After US exposure (0.08 MHz, 1.0 W/cm(2), 50%
      duty cycle, and 10-min duration), the biofilms were cultured at 37  degrees C for
      another 12 h. The results showed that many micropores were found in biofilms
      treated with vancomycin combined with UTMD. Biofilm densities (A(570) values) and
      the viable counts of S. epidermidis recovered from the biofilm were significantly
      decreased compared with those of any other groups. Furthermore, the highest
      percentage of dead cells was found, using confocal laser scanning microscopy, in
      the biofilm treated with vancomycin combined with UTMD. The viable counts of
      bacteria in biofilms in an in vivo rabbit model also confirmed the enhanced
      effect of vancomycin combined with UTMD. UTMD may have great potential for
      improving antibiotic activity against biofilm infections.

PMID- 21844320
TI  - Discovery of a novel class of orally active antifungal beta-1,3-D-glucan synthase
      inhibitors.
AB  - The echinocandins are a class of semisynthetic natural products that target beta
      1,3-glucan synthase (GS). Their proven clinical efficacy combined with minimal
      safety issues has made the echinocandins an important asset in the management of
      fungal infection in a variety of patient populations. However, the echinocandins
      are delivered only parenterally. A screen for antifungal bioactivities combined
      with mechanism-of-action studies identified a class of piperazinyl-pyridazinones
      that target GS. The compounds exhibited in vitro activity comparable, and in some
      cases superior, to that of the echinocandins. The compounds inhibit GS in vitro,
      and there was a strong correlation between enzyme inhibition and in vitro
      antifungal activity. In addition, like the echinocandins, the compounds caused a
      leakage of cytoplasmic contents from yeast and produced a morphological response
      in molds characteristic of GS inhibitors. Spontaneous mutants of Saccharomyces
      cerevisiae with reduced susceptibility to the piperazinyl-pyridazinones had
      substitutions in FKS1. The sites of these substitutions were distinct from those
      conferring resistance to echinocandins; likewise, echinocandin-resistant isolates
      remained susceptible to the test compounds. Finally, we present efficacy and
      pharmacokinetic data on an example of the piperazinyl-pyridazinone compounds that
      demonstrated efficacy in a murine model of Candida glabrata infection.

PMID- 21844321
TI  - Clofazimine analogs with efficacy against experimental tuberculosis and reduced
      potential for accumulation.
AB  - The global tuberculosis crisis urgently demands new, efficacious, orally
      available drugs with the potential to shorten and simplify the long and complex
      treatments for drug-sensitive and drug-resistant disease. Clofazimine, a
      riminophenazine used for many years to treat leprosy, demonstrates efficacy in
      animal models of tuberculosis via a novel mode of action. However, clofazimine's
      physicochemical and pharmacokinetic properties contribute to side effects that
      limit its use; in particular, an extremely long half-life and propensity for
      tissue accumulation together with clofazimine's dye properties leads to unwelcome
      skin discoloration. We recently conducted a systematic structure-activity study
      of more than 500 riminophenazine analogs for anti-Mycobacterium tuberculosis
      activity. We describe here the characteristics of 12 prioritized compounds in
      more detail. The new riminophenazine analogs demonstrated enhanced in vitro
      activity compared to clofazimine against replicating M. tuberculosis H37Rv, as
      well as panels of drug-sensitive and drug-resistant clinical isolates. The new
      compounds demonstrate at least equivalent activity compared to clofazimine
      against intracellular M. tuberculosis and, in addition, most of them were active
      against nonreplicating M. tuberculosis. Eleven of these more water-soluble
      riminophenazine analogs possess shorter half-lives than clofazimine when dosed
      orally to mice, suggesting that they may accumulate less. Most importantly, the
      nine compounds that progressed to efficacy testing demonstrated inhibition of
      bacterial growth in the lungs that is superior to the activity of an equivalent
      dose of clofazimine when administered orally for 20 days in a murine model of
      acute tuberculosis. The efficacy of these compounds, along with their decreased
      potential for accumulation and therefore perhaps also for tissue discoloration,
      warrants further study.

PMID- 21844322
TI  - Selective killing of bacterial persisters by a single chemical compound without
      affecting normal antibiotic-sensitive cells.
AB  - We show that 3-[4-(4-methoxyphenyl)piperazin-1-yl]piperidin-4-yl biphenyl-4
      carboxylate (C10), screened out of a chemical library, selectively kills
      bacterial persisters that tolerate antibiotic treatment but does not affect
      normal antibiotic-sensitive cells. C10 led persisters to antibiotic-induced cell
      death by causing reversion of persisters to antibiotic-sensitive cells. This work
      is the first demonstration in which the eradication of bacterial persisters is
      based on single-chemical supplementation. The chemical should be versatile in
      elucidating the mechanism of persistence.

PMID- 21844323
TI  - Identification of protein-protein interaction inhibitors targeting vaccinia virus
      processivity factor for development of antiviral agents.
AB  - Poxvirus uracil DNA glycosylase D4 in association with A20 and the catalytic
      subunit of DNA polymerase forms the processive polymerase complex. The binding of
      D4 and A20 is essential for processive polymerase activity. Using an AlphaScreen
      assay, we identified compounds that inhibit protein-protein interactions between
      D4 and A20. Effective interaction inhibitors exhibited both antiviral activity
      and binding to D4. These results suggest that novel antiviral agents that target
      the protein-protein interactions between D4 and A20 can be developed for the
      treatment of infections with poxviruses, including smallpox.

PMID- 21844324
TI  - Anidulafungin in treatment of experimental invasive infection by Candida
      parapsilosis: in vitro activity, (1-->3)-beta-D-glucan and mannan serum levels,
      histopathological findings, and in vivo efficacy.
AB  - We have evaluated the in vitro activity of anidulafungin (AFG) against 31 strains
      of Candida parapsilosis sensu stricto by using broth microdilution, disk
      diffusion, and minimal fungicidal concentration (MFC) determination procedures.
      The two first methods showed a high level of activity of the drug, while MFCs
      were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs
      were predictive of in vivo outcomes, six strains representing different AFG MICs
      (0.12 to 2 MUg/ml) were tested in a murine model of disseminated infection
      treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG
      was able to prolong the survival of mice infected with all the strains tested but
      was able to reduce the tissue burden of those mice infected only with the strains
      that showed the lowest MIC (0.12 MUg/ml).

PMID- 21844325
TI  - Functional characterization of Tn4401, a Tn3-based transposon involved in blaKPC
      gene mobilization.
AB  - The carbapenemase gene bla(KPC), which is rapidly spreading worldwide, is located
      on a Tn3-based transposon, Tn4401. In a transposition-conjugation assay, Tn4401
      was able to mobilize bla(KPC-2) gene at a frequency of 4.4 * 10(-6)/recipient
      cell. A 5-bp target site duplication was evidenced upon each insertion without
      target site specificity. This study demonstrated that Tn4401 is an active
      transposon capable of mobilizing bla(KPC) genes at high frequency.

PMID- 21844326
TI  - Cellular assay optimization: part II: the use of a simple integrated robotic work
      cell to allow the multiplexed batching of cellular assays.
AB  - This report describes the implementation of an automated work cell with
      commercially available hardware and software, capable of handling up to 15
      separate reagents for performing 96-well or 384-well assays but with a small
      footprint and only a single liquid dispenser and two plate washers. Extremely
      flexible software was used to enable this simple work cell to perform processes
      that would traditionally require a much larger, more expensive automation
      platform. With the development of the C-Myc assays for the targets DYRK, BMX,
      PERK, and FAK, the authors describe a software solution to multibatch assays to
      run simultaneously, reducing reagent dead volume and increasing the efficiency of
      running multiple assays such that the time to generate data across multiple
      targets was significantly shortened. Although a larger automated system with
      multiple robotic arms and extensive equipment would also be able to process
      multiple assays simultaneously, the work cell we have described represents an
      inexpensive and flexible, easily upgradable option suitable for a wider range of
      labs.

PMID- 21844327
TI  - Bioluminescent method for assaying multiple semicarbazide-sensitive amine oxidase
      (SSAO) family members in both 96- and 384-well formats.
AB  - Vascular adhesion protein-1 (VAP-1), also known as semicarbazide-sensitive amine
      oxidase (SSAO) or copper-containing amine oxidase (AOC3, EC 1.4.3.6), catalyzes
      oxidative deamination of primary amines. One endogenous substrate has recently
      been described (Siglec 10), and although its mechanism of action in vivo is not
      completely understood, it is suggested to play a role in immune cell trafficking,
      making it a target of interest for autoimmune and inflammatory diseases. Much of
      the enzymology performed around this target has been conducted with absorbance,
      fluorescent, or radiometric formats that can have some limitations for high
      throughput screening and subsequent compound profiling. The authors present the
      use of a bioluminescent assay, originally developed for monoamine oxidase
      enzymes, in a high-throughput format. It can be used for related SSAOs such as
      AOC1 given their substrate similarity with VAP-1. The authors also demonstrate
      that it is compatible with different sources of VAP-1, both purified recombinant
      and VAP-1 overexpressed on live cells.

PMID- 21844329
TI  - Antigen fingerprinting of polyclonal antibodies raised in immunized chickens with
      tick total proteins: a reservoir for the discovery of novel antigens.
AB  - Identification of tick-protective antigens remains the limiting step in vaccine
      development. The authors have generated several B cell epitope candidates by
      fingerprinting Rhipicephalus (Boophilus) microplus proteins that were
      characterized through bioselection of random peptide phage display libraries
      against polyclonal antibodies antitick proteins. From 280 clones selected and
      sequenced, 107 distinct reactive clones were validated by dot-blot assays. Eight
      consensus motifs were generated, and the most frequent ones were PXXKXH, NXXKXXL,
      and HTS (68.2%, 65%, and 42%, respectively). The consensus sequences identified
      potential vaccine targets by alignment with the protein database of R. microplus,
      which may have putative roles in the host response. Sequences that did not align
      with known proteins but shared extensive homology among each other were
      classified as conformational epitopes. Sequence alignments also recognized
      multiple targets, and the most predominant proteins were identified. Finally,
      immunized mice sera recognized tick proteins, demonstrating that functional
      epitope profiles can be identified through selection of phage-displayed peptide
      libraries with hyperimmune sera and revealing that the epitope-displaying phages
      can be used as potential vaccine immunogens.

PMID- 21844330
TI  - Structure of the budding yeast Saccharomyces cerevisiae centromeric histones Cse4
      H4 complexed with the chaperone Scm3.

PMID- 21844328
TI  - Complementary cell-based high-throughput screens identify novel modulators of the
      unfolded protein response.
AB  - Despite advances toward understanding the prevention and treatment of many
      cancers, patients who suffer from oral squamous cell carcinoma (OSCC) confront a
      survival rate that has remained unimproved for more than 2 decades, indicating
      our ability to treat them pharmacologically has reached a plateau. In an ongoing
      effort to improve the clinical outlook for this disease, we previously reported
      that an essential component of the mechanism by which the proteasome inhibitor
      bortezomib (PS-341, Velcade) induced apoptosis in OSCC required the activation of
      a terminal unfolded protein response (UPR). Predicated on these studies, the
      authors hypothesized that high-throughput screening (HTS) of large diverse
      chemical libraries might identify more potent or selective small-molecule
      activators of the apoptotic arm of the UPR to control or kill OSCC. They have
      developed complementary cell-based assays using stably transfected CHO-K1 cell
      lines that individually assess the PERK/eIF2alpha/CHOP (apoptotic) or the
      IRE1/XBP1 (adaptive) UPR subpathways. An 66 K compound collection was screened at
      the University of Michigan Center for Chemical Genomics that included a unique
      library of prefractionated natural product extracts. The mycotoxin
      methoxycitrinin was isolated from a natural extract and found to selectively
      activate the CHOP-luciferase reporter at 80 uM. A series of citrinin derivatives
      was isolated from these extracts, including a unique congener that has not been
      previously described. In an effort to identify more potent compounds, the authors
      examined the ability of citrinin and the structurally related mycotoxins
      ochratoxin A and patulin to activate the UPR. Strikingly, it was found that
      patulin at 2.5 to 10 uM induced a terminal UPR in a panel of OSCC cells that was
      characterized by an increase in CHOP, GADD34, and ATF3 gene expression and XBP1
      splicing. A luminescent caspase assay and the induction of several BH3-only genes
      indicated that patulin could induce apoptosis in OSCC cells. These data support
      the use of this complementary HTS strategy to identify novel modulators of UPR
      signaling and tumor cell death.

PMID- 21844331
TI  - Divergent ecosystem responses within a benthic marine community to ocean
      acidification.
AB  - Ocean acidification is predicted to impact all areas of the oceans and affect a
      diversity of marine organisms. However, the diversity of responses among species
      prevents clear predictions about the impact of acidification at the ecosystem
      level. Here, we used shallow water CO(2) vents in the Mediterranean Sea as a
      model system to examine emergent ecosystem responses to ocean acidification in
      rocky reef communities. We assessed in situ benthic invertebrate communities in
      three distinct pH zones (ambient, low, and extreme low), which differed in both
      the mean and variability of seawater pH along a continuous gradient. We found
      fewer taxa, reduced taxonomic evenness, and lower biomass in the extreme low pH
      zones. However, the number of individuals did not differ among pH zones,
      suggesting that there is density compensation through population blooms of small
      acidification-tolerant taxa. Furthermore, the trophic structure of the
      invertebrate community shifted to fewer trophic groups and dominance by
      generalists in extreme low pH, suggesting that there may be a simplification of
      food webs with ocean acidification. Despite high variation in individual species'
      responses, our findings indicate that ocean acidification decreases the
      diversity, biomass, and trophic complexity of benthic marine communities. These
      results suggest that a loss of biodiversity and ecosystem function is expected
      under extreme acidification scenarios.

PMID- 21844332
TI  - Parallel adaptive feedback enhances reliability of the Ca2+ signaling system.
AB  - Despite large cell-to-cell variations in the concentrations of individual
      signaling proteins, cells transmit signals correctly. This phenomenon raises the
      question of what signaling systems do to prevent a predicted high failure rate.
      Here we combine quantitative modeling, RNA interference, and targeted selective
      reaction monitoring (SRM) mass spectrometry, and we show for the ubiquitous and
      fundamental calcium signaling system that cells monitor cytosolic and endoplasmic
      reticulum (ER) Ca(2+) levels and adjust in parallel the concentrations of the
      store-operated Ca(2+) influx mediator stromal interaction molecule (STIM), the
      plasma membrane Ca(2+) pump plasma membrane Ca-ATPase (PMCA), and the ER Ca(2+)
      pump sarco/ER Ca(2+)-ATPase (SERCA). Model calculations show that this combined
      parallel regulation in protein expression levels effectively stabilizes basal
      cytosolic and ER Ca(2+) levels and preserves receptor signaling. Our results
      demonstrate that, rather than directly controlling the relative level of
      signaling proteins in a forward regulation strategy, cells prevent transmission
      failure by sensing the state of the signaling pathway and using multiple parallel
      adaptive feedbacks.

PMID- 21844333
TI  - Maternal separation produces lasting changes in cortisol and behavior in rhesus
      monkeys.
AB  - Maternal separation (MS), which can lead to hypothalamic pituitary adrenal axis
      dysfunction and behavioral abnormalities in rhesus monkeys, is frequently used to
      model early adversity. Whether this deleterious effect on monkeys is reversible
      by later experience is unknown. In this study, we assessed the basal hair
      cortisol in rhesus monkeys after 1.5 and 3 y of normal social life following an
      early separation. These results showed that peer-reared monkeys had significantly
      lower basal hair cortisol levels than the mother-reared monkeys at both years
      examined. The plasma cortisol was assessed in the monkeys after 1.5 y of normal
      social life, and the results indicated that the peak in the peer-reared cortisol
      response to acute stressors was substantially delayed. In addition, after 3 y of
      normal social life, abnormal behavioral patterns were identified in the peer
      reared monkeys. They showed decreases in locomotion and initiated sitting
      together, as well as increases in stereotypical behaviors compared with the
      mother-reared monkeys. These results demonstrate that the deleterious effects of
      MS on rhesus monkeys cannot be compensated by a later normal social life,
      suggesting that the effects of MS are long-lasting and that the maternal
      separated rhesus monkeys are a good animal model to study early adversity and to
      investigate the development of psychiatric disorders induced by exposure to early
      adversity.

PMID- 21844334
TI  - Slow intrinsic rhythm in the koniocellular visual pathway.
AB  - Slow rhythmic changes in nerve-cell activity are characteristic of unconscious
      brain states and also may contribute to waking brain function by coordinating
      activity between cortical and subcortical structures. Here we show that slow
      rhythms are exhibited by the koniocellular (K) pathway, one of three visual
      pathways beginning in the eye and projecting through the lateral geniculate
      visual relay nucleus to the cerebral cortex. We recorded activity in pairs and
      ensembles of neurons in the lateral geniculate nucleus of anesthetized marmoset
      monkeys. We found slow rhythms are common in K cells but are rare in
      parvocellular and magnocellular cell pairs. The time course of slow K rhythms
      corresponds to subbeta (<10 Hz) EEG frequencies, and high spike rates in K cells
      are associated with low power in the theta and delta EEG bands. By contrast,
      spontaneous activity in the parvocellular and magnocellular pathways is neither
      synchronized nor strongly linked to EEG state. These observations suggest that
      parallel visual pathways not only carry different kinds of visual signals but
      also contribute differentially to brain circuits at the first synapse in the
      thalamus. Differential contribution of sensory streams to rhythmic brain circuits
      also raises the possibility that sensory stimuli can be tailored to modify brain
      rhythms.

PMID- 21844336
TI  - Palmitoylation controls the dynamics of budding-yeast heterochromatin via the
      telomere-binding protein Rif1.
AB  - The posttranslational addition of palmitate to cysteines occurs ubiquitously in
      eukaryotic cells, where it functions in anchoring target proteins to membranes
      and in vesicular trafficking. Here we show that the Saccharomyces cerevisiae
      palmitoyltransferase Pfa4 enhanced heterochromatin formation at the cryptic
      mating-type loci HMR and HML via Rif1, a telomere regulatory protein. Acylated
      Rif1 was detected in extracts from wild-type but not pfa4Delta mutant cells. In a
      pfa4Delta mutant, Rif1-GFP dispersed away from foci positioned at the nuclear
      periphery into the nucleoplasm. Sir3-GFP distribution was also perturbed,
      indicating a change in the nuclear dynamics of heterochromatin proteins. Genetic
      analyses indicated that PFA4 functioned upstream of RIF1. Surprisingly, the
      pfa4Delta mutation had only mild effects on telomeric regulation, suggesting
      Rif1's roles at HM loci and telomeres were more complexly related than previously
      thought. These data supported a model in which Pfa4-dependent palmitoylation of
      Rif1 anchored it to the inner nuclear membrane, influencing its role in
      heterochromatin dynamics.

PMID- 21844337
TI  - Conjugative DNA transfer into human cells by the VirB/VirD4 type IV secretion
      system of the bacterial pathogen Bartonella henselae.
AB  - Bacterial type IV secretion systems (T4SS) mediate interbacterial conjugative DNA
      transfer and transkingdom protein transfer into eukaryotic host cells in
      bacterial pathogenesis. The sole bacterium known to naturally transfer DNA into
      eukaryotic host cells via a T4SS is the plant pathogen Agrobacterium tumefaciens.
      Here we demonstrate T4SS-mediated DNA transfer from a human bacterial pathogen
      into human cells. We show that the zoonotic pathogen Bartonella henselae can
      transfer a cryptic plasmid occurring in the bartonellae into the human
      endothelial cell line EA.hy926 via its T4SS VirB/VirD4. DNA transfer into
      EA.hy926 cells was demonstrated by using a reporter derivative of this Bartonella
      specific mobilizable plasmid generated by insertion of a eukaryotic egfp
      expression cassette. Fusion of the C-terminal secretion signal of the endogenous
      VirB/VirD4 protein substrate BepD with the plasmid-encoded DNA-transport protein
      Mob resulted in a 100-fold increased DNA transfer rate. Expression of the
      delivered egfp gene in EA.hy926 cells required cell division, suggesting that
      nuclear envelope breakdown may facilitate passive entry of the transferred ssDNA
      into the nucleus as prerequisite for complementary strand synthesis and
      transcription of the egfp gene. Addition of an eukaryotic neomycin
      phosphotransferase expression cassette to the reporter plasmid facilitated
      selection of stable transgenic EA.hy926 cell lines that display chromosomal
      integration of the transferred plasmid DNA. Our data suggest that T4SS-dependent
      DNA transfer into host cells may occur naturally during human infection with
      Bartonella and that these chronically infecting pathogens have potential for the
      engineering of in vivo gene-delivery vectors with applications in DNA vaccination
      and therapeutic gene therapy.

PMID- 21844335
TI  - Sunflower domestication alleles support single domestication center in eastern
      North America.
AB  - Phylogenetic analyses of genes with demonstrated involvement in evolutionary
      transitions can be an important means of resolving conflicting hypotheses about
      evolutionary history or process. In sunflower, two genes have previously been
      shown to have experienced selective sweeps during its early domestication. In the
      present study, we identified a third candidate early domestication gene and
      conducted haplotype analyses of all three genes to address a recent,
      controversial hypothesis about the origin of cultivated sunflower. Although the
      scientific consensus had long been that sunflower was domesticated once in
      eastern North America, the discovery of pre-Columbian sunflower remains at
      archaeological sites in Mexico led to the proposal of a second domestication
      center in southern Mexico. Previous molecular studies with neutral markers were
      consistent with the former hypothesis. However, only two indigenous Mexican
      cultivars were included in these studies, and their provenance and genetic purity
      have been questioned. Therefore, we sequenced regions of the three candidate
      domestication genes containing SNPs diagnostic for domestication from large,
      newly collected samples of Mexican sunflower landraces and Mexican wild
      populations from a broad geographic range. The new germplasm also was genotyped
      for 12 microsatellite loci. Our evidence from multiple evolutionarily important
      loci and from neutral markers supports a single domestication event for extant
      cultivated sunflower in eastern North America.

PMID- 21844338
TI  - Protection from UV-induced skin carcinogenesis by genetic inhibition of the
      ataxia telangiectasia and Rad3-related (ATR) kinase.
AB  - Multiple human epidemiologic studies link caffeinated (but not decaffeinated)
      beverage intake with significant decreases in several types of cancer, including
      highly prevalent UV-associated skin carcinomas. The mechanism by which caffeine
      protects against skin cancer is unknown. Ataxia telangiectasia and Rad3-related
      (ATR) is a replication checkpoint kinase activated by DNA stresses and is one of
      several targets of caffeine. Suppression of ATR, or its downstream target
      checkpoint kinase 1 (Chk1), selectively sensitizes DNA-damaged and malignant
      cells to apoptosis. Agents that target this pathway are currently in clinical
      trials. Conversely, inhibition of other DNA damage response pathways, such as
      ataxia telangiectasia mutated (ATM) and BRCA1, promotes cancer. To determine the
      effect of replication checkpoint inhibition on carcinogenesis, we generated
      transgenic mice with diminished ATR function in skin and crossed them into a UV
      sensitive background, Xpc(-/-). Unlike caffeine, this genetic approach was
      selective and had no effect on ATM activation. These transgenic mice were viable
      and showed no histological abnormalities in skin. Primary keratinocytes from
      these mice had diminished UV-induced Chk1 phosphorylation and twofold
      augmentation of apoptosis after UV exposure (P = 0.006). With chronic UV
      treatment, transgenic mice remained tumor-free for significantly longer (P =
      0.003) and had 69% fewer tumors at the end of observation of the full cohort (P =
      0.019), compared with littermate controls with the same genetic background. This
      study suggests that inhibition of replication checkpoint function can suppress
      skin carcinogenesis and supports ATR inhibition as the relevant mechanism for the
      protective effect of caffeinated beverage intake in human epidemiologic studies.

PMID- 21844339
TI  - Normal hearing is not enough to guarantee robust encoding of suprathreshold
      features important in everyday communication.
AB  - "Normal hearing" is typically defined by threshold audibility, even though
      everyday communication relies on extracting key features of easily audible sound,
      not on sound detection. Anecdotally, many normal-hearing listeners report
      difficulty communicating in settings where there are competing sound sources, but
      the reasons for such difficulties are debated: Do these difficulties originate
      from deficits in cognitive processing, or differences in peripheral, sensory
      encoding? Here we show that listeners with clinically normal thresholds exhibit
      very large individual differences on a task requiring them to focus spatial
      selective auditory attention to understand one speech stream when there are
      similar, competing speech streams coming from other directions. These individual
      differences in selective auditory attention ability are unrelated to age, reading
      span (a measure of cognitive function), and minor differences in absolute hearing
      threshold; however, selective attention ability correlates with the ability to
      detect simple frequency modulation in a clearly audible tone. Importantly, we
      also find that selective attention performance correlates with physiological
      measures of how well the periodic, temporal structure of sounds above the
      threshold of audibility are encoded in early, subcortical portions of the
      auditory pathway. These results suggest that the fidelity of early sensory
      encoding of the temporal structure in suprathreshold sounds influences the
      ability to communicate in challenging settings. Tests like these may help tease
      apart how peripheral and central deficits contribute to communication
      impairments, ultimately leading to new approaches to combat the social isolation
      that often ensues.

PMID- 21844340
TI  - Electrophysiological evidence for the left-lateralized effect of language on
      preattentive categorical perception of color.
AB  - Previous studies have shown that the effect of language on categorical perception
      of color is stronger when stimuli are presented in the right visual field than in
      the left. To examine whether this lateralized effect occurs preattentively at an
      early stage of processing, we monitored the visual mismatch negativity, which is
      a component of the event-related potential of the brain to an unfamiliar stimulus
      among a temporally presented series of stimuli. In the oddball paradigm we used,
      the deviant stimuli were unrelated to the explicit task. A significant
      interaction between color-pair type (within-category vs. between-category) and
      visual field (left vs. right) was found. The amplitude of the visual mismatch
      negativity component evoked by the within-category deviant was significantly
      smaller than that evoked by the between-category deviant when displayed in the
      right visual field, but no such difference was observed for the left visual
      field. This result constitutes electroencephalographic evidence that the
      lateralized Whorf effect per se occurs out of awareness and at an early stage of
      processing.

PMID- 21844341
TI  - Rab3B protein is required for long-term depression of hippocampal inhibitory
      synapses and for normal reversal learning.
AB  - Rab3B, similar to other Rab3 isoforms, is a synaptic vesicle protein that
      interacts with the Rab3-interacting molecule (RIM) isoforms RIM1alpha and
      RIM2alpha as effector proteins in a GTP-dependent manner. Previous studies showed
      that at excitatory synapses, Rab3A and RIM1alpha are essential for
      presynaptically expressed long-term potentiation (LTP), whereas at inhibitory
      synapses RIM1alpha is required for endocannabinoid-dependent long-term depression
      (referred to as "i-LTD"). However, it remained unknown whether i-LTD also
      involves a Rab3 isoform and whether i-LTD, similar to other forms of long-term
      plasticity, is important for learning and memory. Here we show that Rab3B is
      highly enriched in inhibitory synapses in the CA1 region of the hippocampus.
      Using electrophysiological recordings in acute slices, we demonstrate that
      knockout (KO) of Rab3B does not alter the strength or short-term plasticity of
      excitatory or inhibitory synapses but does impair i-LTD significantly without
      changing classical NMDA receptor-dependent LTP. Behaviorally, we found that Rab3B
      KO mice exhibit no detectable changes in all basic parameters tested, including
      the initial phase of learning and memory. However, Rab3B KO mice did display a
      selective enhancement in reversal learning, as measured using Morris water-maze
      and fear-conditioning assays. Our data support the notion that presynaptic forms
      of long-term plasticity at excitatory and inhibitory synapses generally are
      mediated by a common Rab3/RIM-dependent pathway, with various types of synapses
      using distinct Rab3 isoforms. Moreover, our results suggest that i-LTD
      contributes to learning and memory, presumably by stabilizing circuits
      established in previous learning processes.

PMID- 21844342
TI  - Combination therapy utilizing shRNA knockdown and an optimized resistant
      transgene for rescue of diseases caused by misfolded proteins.
AB  - Molecular knockdown of disease proteins and restoration of wild-type activity
      represent a promising but challenging strategy for the treatment of diseases that
      result from the accumulation of misfolded proteins (i.e., Huntington disease,
      amyotrophic lateral sclerosis, and alpha-1 antitrypsin deficiency). In this study
      we used alpha-1 antitrypsin (AAT) deficiency with the piZZ mutant phenotype as a
      model system to evaluate the efficiency of gene-delivery approaches that both
      silence the piZZ transcript (e.g., shRNA) and restore circulating wild-type AAT
      expression from resistant codon-optimized AAT (AAT-opt) transgene cassette using
      adeno-associated virus (AAV) vector delivery. After systemic injection of a self
      complimentary AAV serotype 8 (scAAV8) vector encoding shRNA in piZZ transgenic
      mice, both mutant AAT mRNA in the liver and defected serum protein level were
      inhibited by 95%, whereas liver pathology, as monitored by dPAS and fibrosis
      staining, reversed. To restore blood AAT levels in AAV8/shRNA-treated mice,
      several strategies to restore functional AAT levels were tested, including using
      AAV AAT-opt transgene cassettes targeted to muscle and liver, or combination
      vectors carrying piZZ shRNA and AAT-opt transgenes separately, or a single
      bicistronic AAV vector. With these molecular approaches, we observed over 90%
      knockdown of mutant AAT with a 13- to 30-fold increase of circulating wild-type
      AAT protein from the shRNA-resistant AAT-opt cassette. The molecular approaches
      applied in this study can simultaneously prevent liver pathology and restore
      blood AAT concentration in AAT deficiencies. Based on these observations, similar
      gene-therapy strategies could be considered for any diseases caused by
      accumulation of misfolded proteins.

PMID- 21844343
TI  - Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous
      system synapses.
AB  - Exocytosis of synaptic vesicles (SVs) during fast synaptic transmission is
      mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) complex assembly formed by the coil-coiling of three members of this
      protein family: vesicle SNARE protein, synaptobrevin 2 (syb2), and the
      presynaptic membrane SNAREs syntaxin-1A and SNAP-25. However, it is
      controversially debated how many SNARE complexes are minimally needed for SV
      priming and fusion. To quantify this effective number, we measured the
      fluorescence responses from single fusing vesicles expressing pHluorin (pHl), a
      pH-sensitive variant of GFP, fused to the luminal domain of the vesicular SNARE
      syb2 (spH) in cultured hippocampal neurons lacking endogenous syb2. Fluorescence
      responses were quantal, with the unitary signals precisely corresponding to
      single pHluorin molecules. Using this approach we found that two copies of spH
      per SV fully rescued evoked fusion whereas SVs expressing only one spH were
      unable to rapidly fuse upon stimulation. Thus, two syb2 molecules and likely two
      SNARE complexes are necessary and sufficient for SV fusion during fast synaptic
      transmission.

PMID- 21844344
TI  - Fusion-activated Ca2+ entry via vesicular P2X4 receptors promotes fusion pore
      opening and exocytotic content release in pneumocytes.
AB  - Ca(2+) is considered a key element in multiple steps during regulated exocytosis.
      During the postfusion phase, an elevated cytoplasmic Ca(2+) concentration
      ([Ca(2+)])(c) leads to fusion pore dilation. In neurons and neuroendocrine cells,
      this results from activation of voltage-gated Ca(2+) channels in the plasma
      membrane. However, these channels are activated in the prefusion stage, and
      little is known about Ca(2+) entry mechanisms during the postfusion stage. This
      may be particularly important for slow and nonexcitable secretory cells. We
      recently described a "fusion-activated" Ca(2+) entry (FACE) mechanism in alveolar
      type II (ATII) epithelial cells. FACE follows initial fusion pore opening with a
      delay of 200-500 ms. The site, molecular mechanisms, and functions of this
      mechanism remain unknown, however. Here we show that vesicle-associated Ca(2+)
      channels mediate FACE. Using RT-PCR, Western blot analysis, and
      immunofluorescence, we demonstrate that P2X(4) receptors are expressed on
      exocytotic vesicles known as lamellar bodies (LBs). Electrophysiological,
      pharmacological, and genetic data confirm that FACE is mediated via these
      vesicular P2X(4) receptors. Furthermore, analysis of fluorophore diffusion into
      and out of individual vesicles after exocytotic fusion provides evidence that
      FACE regulates postfusion events of LB exocytosis via P2X(4). Fusion pore
      dilation was clearly correlated with the amplitude of FACE, and content release
      from fused LBs was accelerated in fusions followed by FACE. Based on these
      findings, we propose a model for regulation of the exocytotic postfusion phase in
      nonexcitable cells in which Ca(2+) influx via vesicular Ca(2+) channels regulates
      fusion pore expansion and vesicle content release.

PMID- 21844346
TI  - Fine tuning by human CD1e of lipid-specific immune responses.
AB  - CD1e is a member of the CD1 family that participates in lipid antigen
      presentation without interacting with the T-cell receptor. It binds lipids in
      lysosomes and facilitates processing of complex glycolipids, thus promoting
      editing of lipid antigens. We find that CD1e may positively or negatively affect
      lipid presentation by CD1b, CD1c, and CD1d. This effect is caused by the capacity
      of CD1e to facilitate rapid formation of CD1-lipid complexes, as shown for CD1d,
      and also to accelerate their turnover. Similar results were obtained with antigen
      presenting cells from CD1e transgenic mice in which lipid complexes are assembled
      more efficiently and show faster turnover than in WT antigen-presenting cells.
      These effects maximize and temporally narrow CD1-restricted responses, as shown
      by reactivity to Sphingomonas paucimobilis-derived lipid antigens. CD1e is
      therefore an important modulator of both group 1 and group 2 CD1-restricted
      responses influencing the lipid antigen availability as well as the generation
      and persistence of CD1-lipid complexes.

PMID- 21844345
TI  - Architecture of human telomerase RNA.
AB  - Telomerase is a unique reverse transcriptase that catalyzes the addition of
      telomere DNA repeats onto the 3' ends of linear chromosomes and plays a critical
      role in maintaining genome stability. Unlike other reverse transcriptases,
      telomerase is unique in that it is a ribonucleoprotein complex, where the RNA
      component [telomerase RNA (TR)] not only provides the template for the synthesis
      of telomere DNA repeats but also plays essential roles in catalysis,
      accumulation, TR 3'-end processing, localization, and holoenzyme assembly.
      Biochemical studies have identified TR elements essential for catalysis that
      share remarkably conserved secondary structures across different species as well
      as species-specific domains for other functions, paving the way for high
      resolution structure determination of TRs. Over the past decade, structures of
      key elements from the core, conserved regions 4 and 5, and small Cajal body
      specific RNA domains of human TR have emerged, providing significant insights
      into the roles of these RNA elements in telomerase function. Structures of all
      helical elements of the core domain have been recently reported, providing the
      basis for a high-resolution model of the complete core domain. We review this
      progress to determine the overall architecture of human telomerase RNA.

PMID- 21844347
TI  - Augmin promotes meiotic spindle formation and bipolarity in Xenopus egg extracts.
AB  - Female meiotic spindles in many organisms form in the absence of centrosomes, the
      organelle typically associated with microtubule (MT) nucleation. Previous studies
      have proposed that these meiotic spindles arise from RanGTP-mediated MT
      nucleation in the vicinity of chromatin; however, whether this process is
      sufficient for spindle formation is unknown. Here, we investigated whether a
      recently proposed spindle-based MT nucleation pathway that involves augmin, an 8
      subunit protein complex, also contributes to spindle morphogenesis. We used an
      assay system in which hundreds of meiotic spindles can be observed forming around
      chromatin-coated beads after introduction of Xenopus egg extracts. Spindles
      forming in augmin-depleted extracts showed reduced rates of MT formation and were
      predominantly multipolar, revealing a function of augmin in stabilizing the
      bipolar shape of the acentrosomal meiotic spindle. Our studies also have
      uncovered an apparent augmin-independent MT nucleation process from acentrosomal
      poles, which becomes increasingly active over time and appears to partially
      rescue the spindle defects that arise from augmin depletion. Our studies reveal
      that spatially and temporally distinct MT generation pathways from chromatin,
      spindle MTs, and acentrosomal poles all contribute to robust bipolar spindle
      formation in meiotic extracts.

PMID- 21844348
TI  - Chloroplast lipid droplet type II NAD(P)H quinone oxidoreductase is essential for
      prenylquinone metabolism and vitamin K1 accumulation.
AB  - Lipid droplets are ubiquitous cellular structures in eukaryotes and are required
      for lipid metabolism. Little is currently known about plant lipid droplets other
      than oil bodies. Here, we define dual roles for chloroplast lipid droplets
      (plastoglobules) in energy and prenylquinone metabolism. The prenylquinones-
      plastoquinone, plastochromanol-8, phylloquinone (vitamin K(1)), and tocopherol
      (vitamin E)--are partly stored in plastoglobules. This work shows that NAD(P)H
      dehydrogenase C1 (NDC1) (At5g08740), a type II NAD(P)H quinone oxidoreductase,
      associates with plastoglobules. NDC1 reduces a plastoquinone analog in vitro and
      affects the overall redox state of the total plastoquinone pool in vivo by
      reducing the plastoquinone reservoir of plastoglobules. Finally, NDC1 is required
      for normal plastochromanol-8 accumulation and is essential for vitamin K(1)
      production.

PMID- 21844349
TI  - Profile of Gary Ruvkun.

PMID- 21844350
TI  - Large-scale navigational map in a mammal.
AB  - Navigation, the ability to reach desired goal locations, is critical for animals
      and humans. Animal navigation has been studied extensively in birds, insects, and
      some marine vertebrates and invertebrates, yet we are still far from elucidating
      the underlying mechanisms in other taxonomic groups, especially mammals. Here we
      report a systematic study of the mechanisms of long-range mammalian navigation.
      High-resolution global positioning system tracking of bats was conducted here,
      which revealed high, fast, and very straight commuting flights of Egyptian fruit
      bats (Rousettus aegyptiacus) from their cave to remote fruit trees. Bats returned
      to the same individual trees night after night. When displaced 44 km south, bats
      homed directly to one of two goal locations--familiar fruit tree or cave--ruling
      out beaconing, route-following, or path-integration mechanisms. Bats released 84
      km south, within a deep natural crater, were initially disoriented (but
      eventually left the crater toward the home direction and homed successfully),
      whereas bats released at the crater-edge top homed directly, suggesting
      navigation guided primarily by distal visual landmarks. Taken together, these
      results provide evidence for a large-scale "cognitive map" that enables
      navigation of a mammal within its visually familiar area, and they also
      demonstrate the ability to home back when translocated outside the visually
      familiar area.

PMID- 21844351
TI  - Boundary work for sustainable development: Natural resource management at the
      Consultative Group on International Agricultural Research (CGIAR).
AB  - Previous research on the determinants of effectiveness in knowledge systems
      seeking to support sustainable development has highlighted the importance of
      "boundary work" through which research communities organize their relations with
      new science, other sources of knowledge, and the worlds of action and
      policymaking. A growing body of scholarship postulates specific attributes of
      boundary work that promote used and useful research. These propositions, however,
      are largely based on the experience of a few industrialized countries. We report
      here on an effort to evaluate their relevance for efforts to harness science in
      support of sustainability in the developing world. We carried out a multicountry
      comparative analysis of natural resource management programs conducted under the
      auspices of the Consultative Group on International Agricultural Research. We
      discovered six distinctive kinds of boundary work contributing to the successes
      of those programs-a greater variety than has been documented in previous studies.
      We argue that these different kinds of boundary work can be understood as a dual
      response to the different uses for which the results of specific research
      programs are intended, and the different sources of knowledge drawn on by those
      programs. We show that these distinctive kinds of boundary work require
      distinctive strategies to organize them effectively. Especially important are
      arrangements regarding participation of stakeholders, accountability in
      governance, and the use of "boundary objects." We conclude that improving the
      ability of research programs to produce useful knowledge for sustainable
      development will require both greater and differentiated support for multiple
      forms of boundary work. 

PMID- 21844352
TI  - OCT4 establishes and maintains nucleosome-depleted regions that provide
      additional layers of epigenetic regulation of its target genes.
AB  - Recent epigenome-wide mapping studies describe nucleosome-depleted regions (NDRs)
      at transcription start sites and enhancers. However, these static maps do not
      address causality or the roles of NDRs in gene control, and their relationship to
      transcription factors and DNA methylation is not well understood. Using a high
      resolution single-molecule mapping approach to simultaneously investigate
      endogenous DNA methylation and nucleosome occupancies on individual DNA
      molecules, we show that the unmethylated OCT4 distal enhancer has an NDR, whereas
      NANOG has a clear NDR at its proximal promoter. These NDRs are maintained by
      binding of OCT4 and are required for OCT4 and NANOG expression. Differentiation
      causes a rapid loss of both NDRs accompanied by nucleosome occupancy, which
      precedes de novo DNA methylation. NDRs can be restored by forced expression of
      OCT4 in somatic cells but only when there is no cytosine methylation. These data
      show the central role of the NDRs, established by OCT4, in ensuring the
      autoregulatory loop of pluripotency and, furthermore, that de novo methylation
      follows the loss of NDRs and stabilizes the suppressed state.

PMID- 21844354
TI  - Flow regime, temperature, and biotic interactions drive differential declines of
      trout species under climate change.
AB  - Broad-scale studies of climate change effects on freshwater species have focused
      mainly on temperature, ignoring critical drivers such as flow regime and biotic
      interactions. We use downscaled outputs from general circulation models coupled
      with a hydrologic model to forecast the effects of altered flows and increased
      temperatures on four interacting species of trout across the interior western
      United States (1.01 million km(2)), based on empirical statistical models built
      from fish surveys at 9,890 sites. Projections under the 2080s A1B emissions
      scenario forecast a mean 47% decline in total suitable habitat for all trout, a
      group of fishes of major socioeconomic and ecological significance. We project
      that native cutthroat trout Oncorhynchus clarkii, already excluded from much of
      its potential range by nonnative species, will lose a further 58% of habitat due
      to an increase in temperatures beyond the species' physiological optima and
      continued negative biotic interactions. Habitat for nonnative brook trout
      Salvelinus fontinalis and brown trout Salmo trutta is predicted to decline by 77%
      and 48%, respectively, driven by increases in temperature and winter flood
      frequency caused by warmer, rainier winters. Habitat for rainbow trout,
      Oncorhynchus mykiss, is projected to decline the least (35%) because negative
      temperature effects are partly offset by flow regime shifts that benefit the
      species. These results illustrate how drivers other than temperature influence
      species response to climate change. Despite some uncertainty, large declines in
      trout habitat are likely, but our findings point to opportunities for strategic
      targeting of mitigation efforts to appropriate stressors and locations.

PMID- 21844353
TI  - Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune
      synapses and are targeted by hepatitis C virus.
AB  - RIG-I is a cytosolic pathogen recognition receptor that engages viral RNA in
      infected cells to trigger innate immune defenses through its adaptor protein
      MAVS. MAVS resides on mitochondria and peroxisomes, but how its signaling is
      coordinated among these organelles has not been defined. Here we show that a
      major site of MAVS signaling is the mitochondrial-associated membrane (MAM), a
      distinct membrane compartment that links the endoplasmic reticulum to
      mitochondria. During RNA virus infection, RIG-I is recruited to the MAM to bind
      MAVS. Dynamic MAM tethering to mitochondria and peroxisomes then coordinates MAVS
      localization to form a signaling synapse between membranes. Importantly, the
      hepatitis C virus NS3/4A protease, which cleaves MAVS to support persistent
      infection, targets this synapse for MAVS proteolysis from the MAM, but not from
      mitochondria, to ablate RIG-I signaling of immune defenses. Thus, the MAM
      mediates an intracellular immune synapse that directs antiviral innate immunity.

PMID- 21844355
TI  - Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded
      proteins.
AB  - The consequence of chronic protein misfolding is the basis of many human
      diseases. To combat the deleterious effects of accumulated protein damage, all
      cells possess robust quality-control systems, specifically molecular chaperones
      and clearance machineries, that sense and respond to protein misfolding. However,
      for many protein conformational diseases, it is unclear why this quality-control
      system does not efficiently counter protein aggregation. Previous findings that
      the heat shock response in Caenorhabditis elegans is regulated by thermosensory
      neurons led us to consider whether neuronal activity could also be responsible
      for the inadequate response of an organism to chronic protein misfolding. Here we
      show, in animals expressing polyglutamine expansion proteins and mutant SOD
      1(G93A) in intestinal or muscle cells, that the nervous system does indeed
      control the cellular response to misfolded proteins. Whereas polyglutamine
      expansion-expressing animals with WT thermosensory neurons readily express
      protein aggregates, leading to cellular dysfunction without concomitant up
      regulation of molecular chaperones, modulation of the nervous system results in
      chaperone up-regulation that suppresses aggregation and toxicity. The neuronal
      signal is transmitted through calcium-activated dense core vesicle
      neurosecretion. Cell-nonautonomous control of chaperone expression by the
      thermosensory neurons allows C. elegans to respond differently to acute stress
      such as heat shock, and chronic stress caused by the expression of misfolded
      proteins, suggesting that neuronal signaling determines the course of cellular
      proteotoxicity.

PMID- 21844356
TI  - US3 protein kinase of HSV-1 cycles between the cytoplasm and nucleus and
      interacts with programmed cell death protein 4 (PDCD4) to block apoptosis.
AB  - The U(S)3 protein kinase of herpes simplex virus 1 plays a key role in blocking
      apoptosis induced by viral gene products or exogenous agents. The U(S)3 protein
      kinase is similar to protein kinase A with respect to substrate range and
      specificity. We report that in the yeast two-hybrid system a domain of U(S)3
      essential for antiapoptotic activity reacted with programmed cell death protein 4
      (PDCD4). We report that U(S)3 interacts with PDCD4, that PDCD4 is
      posttranslationally modified in infected cells both in a U(S)3-dependent and 
      independent fashion, and that depletion of PDCD4 by siRNA blocked apoptosis
      induced by a Deltaalpha4 mutant virus. In infected cells, PDCD4 accumulates in
      the nucleus, whereas U(S)3 accumulates in the cytoplasm. Studies designed to
      elucidate the convergence of these proteins led to the discovery that U(S)3
      protein kinase cycles between the nucleus and cytoplasm and that U(S)3 retains
      PDCD4 in infected cell nuclei.

PMID- 21844357
TI  - Larger amygdala but no change in hippocampal volume in 10-year-old children
      exposed to maternal depressive symptomatology since birth.
AB  - Maternal separation and poor maternal care in animals have been shown to have
      important effects on the developing hippocampus and amygdala. In humans, children
      exposed to abuse/maltreatment or orphanage rearing do not present changes in
      hippocampal volumes. However, children reared in orphanages present enlarged
      amygdala volumes, suggesting that the amygdala may be particularly sensitive to
      severely disturbed (i.e., discontinous, neglectful) care in infancy. Maternal
      depressive symptomatology has been associated with reductions in overall
      sensitivity to the infant, and with an increased rate of withdrawn, disengaged
      behaviors. To determine if poor maternal care associated with maternal depressive
      symptomatology has a similar pattern of association to the volumes of the
      hippocampus and amygdala in children, as is the case for severely disturbed
      infant care (orphanage rearing), we measured hippocampal and amygdala volumes as
      well as stress hormone (glucocorticoid) levels in children exposed (n = 17) or
      not (n = 21) to maternal depressive symptomatology since birth. Results revealed
      no group difference in hippocampal volumes, but larger left and right amygdala
      volumes and increased levels of glucocorticoids in the children of mothers
      presenting depressive symptomatology since birth. Moreover, a significant
      positive correlation was observed between mothers' mean depressive scores and
      amygdala volumes in their children. The results of this study suggest that
      amygdala volume in human children may represent an early marker of biological
      sensitivity to quality of maternal care.

PMID- 21844358
TI  - Differential alteration of two aminopeptidases N associated with resistance to
      Bacillus thuringiensis toxin Cry1Ac in cabbage looper.
AB  - The soil bacterium Bacillus thuringiensis (Bt) is the most successfully used
      biopesticide in agriculture, and its insecticidal protein genes are the primary
      transgenes used for insect control in transgenic crops. However, evolution of
      insect resistance to Bt toxins threatens the long-term future of Bt applications.
      To date, cases of resistance to Bt toxins have been reported in agricultural
      situations in six insect species, but the molecular basis for these cases of
      resistance remains unclear. Here we report that the resistance to the Bt toxin
      Cry1Ac in the cabbage looper, Trichoplusia ni, evolved in greenhouses, is
      associated with differential alteration of two midgut aminopeptidases N, APN1 and
      APN6, conferred by a trans-regulatory mechanism. Biochemical, proteomic, and
      molecular analyses showed that in the Cry1Ac-resistant T. ni, APN1 was
      significantly down-regulated, whereas APN6 was significantly up-regulated. The
      Cry1Ac resistance was correlated with down-regulation of APN1 but not with the up
      regulation of APN6. The concurrent up-regulation of APN6 and down-regulation of
      APN1 might play a role in compensating for the loss of APN1 to minimize the
      fitness costs of the resistance. Along with identifying reduced expression of
      APN1 as the molecular basis of Bt resistance selected in an agricultural setting,
      our findings demonstrate the importance of APN1 to the mode of action of Bt toxin
      Cry1Ac.

PMID- 21844359
TI  - Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng
      derived natural product, panaxytriol.
AB  - We describe herein the discovery of a series of panaxytriol (PXT)-derived
      polyacetylene small molecules with promising cytoprotective activity. In mouse
      xenograft models, we have demonstrated the capacity of our synthetic analogs to
      mitigate a range of cancer therapeutic agent-induced toxicities, including body
      weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have
      also been found to reduce radiation-induced body weight loss and lethality in
      mouse models. Moreover, several PXT analogs appear to exhibit moderate in vivo
      antiinflammatory activity as well as in vitro immunoenhancing capabilities. These
      compounds appear to derive their activity through induction of cancer preventive
      phase 2 enzymes. The studies described herein suggest that coadministration of a
      PXT-derived agent with cancer chemotherapeutics or radiation therapy may serve to
      mitigate a range of therapy-associated toxicities.

PMID- 21844360
TI  - Vascular cell-adhesion molecule-1 plays a central role in the proangiogenic
      effects of oxidative stress.
AB  - Oxidative stress exacerbates neovascularization (NV) in many disease processes.
      In this study we investigated the mechanism of that effect. Mice deficient in
      superoxide dismutase 1 (Sod1(-/-) mice) have increased oxidative stress and show
      severe ocular NV that is reduced to baseline by antioxidants. Compared with wild
      type mice with ischemic retinopathy, Sod1(-/-) mice with ischemic retinopathy had
      increased expression of several NF-kappaB-responsive genes, but expression of
      vascular cell-adhesion molecule-1 (Vcam1) was particularly high. Intraocular
      injection of anti-VCAM-1 antibody eliminated the excessive ischemia-induced
      retinal NV. Elements that contributed to oxidative stress-induced worsening of
      retinal NV that were abrogated by blockade of VCAM-1 included increases in
      leukostasis, influx of bone marrow-derived cells, and capillary closure. Compared
      with ischemia alone, ischemia plus oxidative stress resulted in increased
      expression of several HIF-1-responsive genes caused in part by VCAM-1-induced
      worsening of nonperfusion and, hence, ischemia, because anti-VCAM-1 significantly
      reduced the increased expression of all but one of the genes. These data explain
      why oxidative stress worsens ischemia-induced retinal NV and may be relevant to
      other neovascular diseases in which oxidative stress has been implicated. The
      data also suggest that antagonism of VCAM-1 provides a potential therapy to
      combat worsening of neovascular diseases by oxidative stress.

PMID- 21844361
TI  - S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by
      beta-amyloid peptide.
AB  - The activity of Cdk5 and its regulatory subunit p35 is thought to be important in
      both normal brain function and neurodegenerative disease pathogenesis. Increased
      Cdk5 activity, via proteolytic cleavage of p35 to a p25 fragment by the calcium
      activated protease calpain or by phosphorylation at Cdk5(Tyr15), can contribute
      to neurotoxicity. Nonetheless, our knowledge of regulation of Cdk5 activity in
      disease states is still emerging. Here we demonstrate that Cdk5 is activated by S
      nitrosylation or reaction of nitric oxide (NO)-related species with the thiol
      groups of cysteine residues 83 and 157, to form SNO-Cdk5. We then show that S
      nitrosylation of Cdk5 contributes to amyloid-beta (Abeta) peptide-induced
      dendritic spine loss. Furthermore, we observed significant levels of SNO-Cdk5 in
      postmortem Alzheimer's disease (AD) but not in normal human brains. These
      findings suggest that S-nitrosylation of Cdk5 is an aberrant regulatory mechanism
      of enzyme activity that may contribute to the pathogenesis of AD.

PMID- 21844362
TI  - Eocene habitat shift from saline to freshwater promoted Tethyan amphipod
      diversification.
AB  - Current theory predicts that a shift to a new habitat would increase the rate of
      diversification, while as lineages evolve into multiple species, intensified
      competition would decrease the rate of diversification. We used Holarctic
      amphipods of the genus Gammarus to test this hypothesis. We sequenced four genes
      (5,088 bp) for 289 samples representing 115 Gammarus species. A phylogenetic
      analysis showed that Gammarus originated from the Tethyan region with a saline
      ancestry in the Paleocene, and later colonized the freshwater habitat in the
      Middle Eocene. Ancestral range reconstruction and diversification mode analysis
      combined with paleogeological and paleoclimatic evidence suggested that the
      habitat shift from saline to freshwater led to an increased diversification rate.
      The saline lineage of Gammarus dispersed to both sides of the Atlantic at 55
      million years ago (Ma), because of the few barriers between the Tethys and the
      Atlantic, and diversified throughout its evolutionary history with a constant
      diversification rate [0.04 species per million years (sp/My)]. The freshwater
      Gammarus, however, underwent a rapid diversification phase (0.11 sp/My) until the
      Middle Miocene, and lineages successively diversified across Eurasia via
      vicariance process likely driven by changes of the Tethys and landmass. In
      particular, the freshwater Gammarus lacustris and Gammarus balcanicus lineages
      had a relatively high diversification shift, corresponding to the regression of
      the Paratethys Sea and the continentalization of Eurasian lands during the
      Miocene period. Subsequently (14 Ma), the diversification rate of the freshwater
      Gammarus decreased to 0.05 and again to 0.01 sp/My. The genus Gammarus provides
      an excellent aquatic case supporting the hypothesis that ecological opportunities
      promote diversification.

PMID- 21844363
TI  - Molecular serum portraits in patients with primary breast cancer predict the
      development of distant metastases.
AB  - The risk of distant recurrence in breast cancer patients is difficult to assess
      with current clinical and histopathological parameters, and no validated serum
      biomarkers currently exist. Using a recently developed recombinant antibody
      microarray platform containing 135 antibodies against 65 mainly immunoregulatory
      proteins, we screened 240 sera from 64 patients with primary breast cancer. This
      unique longitudinal sample material was collected from each patient between 0 and
      36 mo after the primary operation. The velocity for each serum protein was
      determined by comparing the samples collected at the primary operation and then 3
      6 mo later. A 21-protein signature was identified, using leave-one-out cross
      validation together with a backward elimination strategy in a training cohort.
      This signature was tested and evaluated subsequently in an independent test
      cohort (prevalidation). The risk of developing distant recurrence after primary
      operation could be assessed for each patient, using her molecular portraits. The
      results from this prevalidation study showed that patients could be classified
      into high- versus low-risk groups for developing metastatic breast cancer with a
      receiver operating characteristic area under the curve of 0.85. This risk
      assessment was not dependent on the type of adjuvant therapy received by the
      patients. Even more importantly, we demonstrated that this protein signature
      provided an added value compared with conventional clinical parameters.
      Consequently, we present here a candidate serum biomarker signature able to
      classify patients with primary breast cancer according to their risk of
      developing distant recurrence, with an accuracy outperforming current procedures.

PMID- 21844364
TI  - Transphyletic conservation of developmental regulatory state in animal evolution.
AB  - Specific regulatory states, i.e., sets of expressed transcription factors, define
      the gene expression capabilities of cells in animal development. Here we explore
      the functional significance of an unprecedented example of regulatory state
      conservation from the cnidarian Nematostella to Drosophila, sea urchin, fish, and
      mammals. Our probe is a deeply conserved cis-regulatory DNA module of the SRY-box
      B2 (soxB2), recognizable at the sequence level across many phyla. Transphyletic
      cis-regulatory DNA transfer experiments reveal that the plesiomorphic control
      function of this module may have been to respond to a regulatory state associated
      with neuronal differentiation. By introducing expression constructs driven by
      this module from any phyletic source into the genomes of diverse developing
      animals, we discover that the regulatory state to which it responds is used at
      different levels of the neurogenic developmental process, including patterning
      and development of the vertebrate forebrain and neurogenesis in the Drosophila
      optic lobe and brain. The regulatory state recognized by the conserved DNA
      sequence may have been redeployed to different levels of the developmental
      regulatory program during evolution of complex central nervous systems.

PMID- 21844365
TI  - Phage auxiliary metabolic genes and the redirection of cyanobacterial host carbon
      metabolism.
AB  - Cyanophages infecting the marine cyanobacteria Prochlorococcus and Synechococcus
      encode and express genes for the photosynthetic light reactions. Sequenced
      cyanophage genomes lack Calvin cycle genes, however, suggesting that
      photosynthetic energy harvested via phage proteins is not used for carbon
      fixation. We report here that cyanophages carry and express a Calvin cycle
      inhibitor, CP12, whose host homologue directs carbon flux from the Calvin cycle
      to the pentose phosphate pathway (PPP). Phage CP12 was coexpressed with phage
      genes involved in the light reactions, deoxynucleotide biosynthesis, and the PPP,
      including a transaldolase gene that is the most prevalent PPP gene in
      cyanophages. Phage transaldolase was purified to homogeneity from several strains
      and shown to be functional in vitro, suggesting that it might facilitate
      increased flux through this key reaction in the host PPP, augmenting production
      of NADPH and ribose 5-phosphate. Kinetic measurements of phage and host
      transaldolases revealed that the phage enzymes have k(cat)/K(m) values only
      approximately one third of the corresponding host enzymes. The lower efficiency
      of phage transaldolase may be a tradeoff for other selective advantages such as
      reduced gene size: we show that more than half of host-like cyanophage genes are
      significantly shorter than their host homologues. Consistent with decreased
      Calvin cycle activity and increased PPP and light reaction activity under
      infection, the host NADPH/NADP ratio increased two-fold in infected cells. We
      propose that phage-augmented NADPH production fuels deoxynucleotide biosynthesis
      for phage replication, and that the selection pressures molding phage genomes
      involve fitness advantages conferred through mobilization of host energy stores.

PMID- 21844366
TI  - Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality
      and germ cell defects.
AB  - Mir-290 through mir-295 (mir-290-295) is a mammalian-specific microRNA (miRNA)
      cluster that, in mice, is expressed specifically in early embryos and embryonic
      germ cells. Here, we show that mir-290-295 plays important roles in embryonic
      development as indicated by the partially penetrant lethality of mutant embryos.
      In addition, we show that in surviving mir-290-295-deficient embryos, female but
      not male fertility is compromised. This impairment in fertility arises from a
      defect in migrating primordial germ cells and occurs equally in male and female
      mutant animals. Male mir-290-295(-/-) mice, due to the extended proliferative
      lifespan of their germ cells, are able to recover from this initial germ cell
      loss and are fertile. Female mir-290-295(-/-) mice are unable to recover and are
      sterile, due to premature ovarian failure.

PMID- 21844368
TI  - Computationally designed adeno-associated virus (AAV) Rep 78 is efficiently
      maintained within an adenovirus vector.
AB  - Adeno-associated virus (AAV) is a single-stranded parvovirus retaining the unique
      capacity for site-specific integration into a transcriptionally silent region of
      the human genome, a characteristic requiring the functional properties of the Rep
      78/68 polypeptide in conjunction with AAV terminal repeat integrating elements.
      Previous strategies designed to assemble these genetic elements into adenoviral
      (Ad) backbones have been limited by the general intolerability of AAV Rep
      sequences, prompting us to computationally reengineer the Rep gene by using
      synonymous codon pair recoding. Rep mutants generated by using de novo genome
      synthesis maintained the polypeptide sequence and endonuclease properties of Rep
      78, while dramatically enhancing Ad replication and viral titer yields,
      characteristics indistinguishable from adenovirus lacking coexpressed Rep.
      Parallel approaches using domain swaps encompassing WT and recoded genomic
      segments, coupled with iterative computational algorithms, collectively
      established that 3' cis-acting Rep genetic elements (and not the Rep 78
      polypeptide) retain dominant-acting sequences inhibiting Ad replication. These
      data provide insights into the molecular relationships of AAV Rep and Ad
      replication, while expanding the applicability of synonymous codon pair
      reengineering as a strategy to effect phenotypic endpoints.

PMID- 21844367
TI  - Increased expression of multifunctional serine protease, HTRA1, in retinal
      pigment epithelium induces polypoidal choroidal vasculopathy in mice.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in the elderly. Wet AMD includes typical choroidal neovascularization
      (CNV) and polypoidal choroidal vasculopathy (PCV). The etiology and pathogenesis
      of CNV and PCV are not well understood. Genome-wide association studies have
      linked a multifunctional serine protease, HTRA1, to AMD. However, the precise
      role of HTRA1 in AMD remains elusive. By transgenically expressing human HTRA1 in
      mouse retinal pigment epithelium, we showed that increased HTRA1 induced cardinal
      features of PCV, including branching networks of choroidal vessels, polypoidal
      lesions, severe degeneration of the elastic laminae, and tunica media of
      choroidal vessels. In addition, HTRA1 mice displayed retinal pigment epithelium
      atrophy and photoreceptor degeneration. Senescent HTRA1 mice developed occult
      CNV, which likely resulted from the degradation of the elastic lamina of Bruch's
      membrane and up-regulation of VEGF. Our results indicate that increased HTRA1 is
      sufficient to cause PCV and is a significant risk factor for CNV.

PMID- 21844369
TI  - Remarkable patterns of surface water ordering around polarized
      buckminsterfullerene.
AB  - Accurate description of water structure affects simulation of protein folding,
      substrate binding, macromolecular recognition, and complex formation. We study
      the hydration of buckminsterfullerene, the smallest hydrophobic nanosphere, by
      molecular dynamics simulations using a state-of-the-art quantum mechanical
      polarizable force field (QMPFF3), derived from quantum mechanical data at the
      MP2/aug-cc-pVTZ(-hp) level augmented by CCSD(T). QMPFF3 calculation of the
      hydrophobic effect is compared to that obtained with empirical force fields.
      Using a novel and highly sensitive method, we see polarization increases ordered
      water structure so that the imprint of the hydrophobic surface atoms on the
      surrounding waters is stronger and extends to long-range. We see less water order
      for empirical force fields. The greater order seen with QMPFF3 will affect
      biological processes through a stronger hydrophobic effect.

PMID- 21844370
TI  - Free radical functionalization of surfaces to prevent adverse responses to
      biomedical devices.
AB  - Immobilizing a protein, that is fully compatible with the patient, on the surface
      of a biomedical device should make it possible to avoid adverse responses such as
      inflammation, rejection, or excessive fibrosis. A surface that strongly binds and
      does not denature the compatible protein is required. Hydrophilic surfaces do not
      induce denaturation of immobilized protein but exhibit a low binding affinity for
      protein. Here, we describe an energetic ion-assisted plasma process that can make
      any surface hydrophilic and at the same time enable it to covalently immobilize
      functional biological molecules. We show that the modification creates free
      radicals that migrate to the surface from a reservoir beneath. When they reach
      the surface, the radicals form covalent bonds with biomolecules. The kinetics and
      number densities of protein molecules in solution and free radicals in the
      reservoir control the time required to form a full protein monolayer that is
      covalently bound. The shelf life of the covalent binding capability is governed
      by the initial density of free radicals and the depth of the reservoir. We show
      that the high reactivity of the radicals renders the binding universal across all
      biological macromolecules. Because the free radical reservoir can be created on
      any solid material, this approach can be used in medical applications ranging
      from cardiovascular stents to heart-lung machines.

PMID- 21844372
TI  - Evidence of neutron leakage at the Fukushima nuclear plant from measurements of
      radioactive 35S in California.
AB  - A recent earthquake and the subsequent tsunami have extensively damaged the
      Fukushima nuclear power plant, releasing harmful radiation into the environment.
      Despite the obvious implication for human health and the surrounding ecology,
      there are no quantitative estimates of the neutron flux leakage during the weeks
      following the earthquake. Here, using measurements of radioactive (35)S contained
      in sulfate aerosols and SO(2) gas at a coastal site in La Jolla, California, we
      show that nearly 4 * 10(11) neutrons per m(2) leaked at the Fukushima nuclear
      power plant before March 20, 2011. A significantly higher (35)SO(2-)(4) activity
      as measured on March 28 is in accord with neutrons escaping the reactor core and
      being absorbed by the coolant seawater (35)Cl to produce (35)S by a (n, p)
      reaction. Once produced, (35)S oxidizes to (35)SO(2) and (35)SO(2-)(4) and was
      then transported to Southern California due to the presence of strong prevailing
      westerly winds at this time. Based on a moving box model, we show that the
      observed activity enhancement in (35)SO(2-)(4) is compatible with long-range
      transport of the radiation plume from Fukushima. Our model predicts that (35)SO(2
      )(4), the concentration in the marine boundary layer at Fukushima, was
      approximately 2 * 10(5) atoms per m(3), which is approximately 365 times above
      expected natural concentrations. These measurements and model calculations imply
      that approximately 0.7% of the total radioactive sulfate present at the marine
      boundary layer at Fukushima reached Southern California as a result of the trans
      Pacific transport.

PMID- 21844371
TI  - WAVE regulatory complex activation by cooperating GTPases Arf and Rac1.
AB  - The WAVE regulatory complex (WRC) is a critical element in the control of actin
      polymerization at the eukaryotic cell membrane, but how WRC is activated remains
      uncertain. While Rho GTPase Rac1 can bind and activate WRC in vitro, this
      interaction is of low affinity, suggesting other factors may be important. By
      reconstituting WAVE-dependent actin assembly on membrane-coated beads in
      mammalian cell extracts, we found that Rac1 was not sufficient to engender bead
      motility, and we uncovered a key requirement for Arf GTPases. In vitro, Rac1 and
      Arf1 were individually able to bind weakly to recombinant WRC and activate it,
      but when both GTPases were bound at the membrane, recruitment and concomitant
      activation of WRC were dramatically enhanced. This cooperativity between the two
      GTPases was sufficient to induce WAVE-dependent bead motility in cell extracts.
      Our findings suggest that Arf GTPases may be central components in WAVE
      signalling, acting directly, alongside Rac1.

PMID- 21844373
TI  - Structural basis of simultaneous recruitment of the transcriptional regulators
      LMO2 and FOG1/ZFPM1 by the transcription factor GATA1.
AB  - The control of red blood cell and megakaryocyte development by the regulatory
      protein GATA1 is a paradigm for transcriptional regulation of gene expression in
      cell lineage differentiation and maturation. Most GATA1-regulated events require
      GATA1 to bind FOG1, and essentially all GATA1-activated genes are cooccupied by a
      TAL1/E2A/LMO2/LDB1 complex; however, it is not known whether FOG1 and
      TAL1/E2A/LMO2/LDB1 are simultaneously recruited by GATA1. Our structural data
      reveal that the FOG1-binding domain of GATA1, the N finger, can also directly
      contact LMO2 and show that, despite the small size (< 50 residues) of the GATA1 N
      finger, both FOG1 and LMO2 can simultaneously bind this domain. LMO2 in turn can
      simultaneously contact both GATA1 and the DNA-binding protein TAL1/E2A at
      bipartite E-box/WGATAR sites. Taken together, our data provide the first
      structural snapshot of multiprotein complex formation at GATA1-dependent genes
      and support a model in which FOG1 and TAL1/E2A/LMO2/LDB1 can cooccupy E
      box/WGATAR sites to facilitate GATA1-mediated activation of gene activation.

PMID- 21844374
TI  - Bestatin-based chemical biology strategy reveals distinct roles for malaria M1-
      and M17-family aminopeptidases.
AB  - Malaria causes worldwide morbidity and mortality, and while chemotherapy remains
      an excellent means of malaria control, drug-resistant parasites necessitate the
      discovery of new antimalarials. Peptidases are a promising class of drug targets
      and perform several important roles during the Plasmodium falciparum erythrocytic
      life cycle. Herein, we report a multidisciplinary effort combining activity-based
      protein profiling, biochemical, and peptidomic approaches to functionally analyze
      two genetically essential P. falciparum metallo-aminopeptidases (MAPs), PfA-M1
      and Pf-LAP. Through the synthesis of a suite of activity-based probes (ABPs)
      based on the general MAP inhibitor scaffold, bestatin, we generated specific ABPs
      for these two enzymes. Specific inhibition of PfA-M1 caused swelling of the
      parasite digestive vacuole and prevented proteolysis of hemoglobin (Hb)-derived
      oligopeptides, likely starving the parasite resulting in death. In contrast,
      inhibition of Pf-LAP was lethal to parasites early in the life cycle, prior to
      the onset of Hb degradation suggesting that Pf-LAP has an essential role outside
      of Hb digestion.

PMID- 21844375
TI  - Adaptation of aerobic respiration to low O2 environments.
AB  - Aerobic respiration in bacteria, Archaea, and mitochondria is performed by oxygen
      reductase members of the heme-copper oxidoreductase superfamily. These enzymes
      are redox-driven proton pumps which conserve part of the free energy released
      from oxygen reduction to generate a proton motive force. The oxygen reductases
      can be divided into three main families based on evolutionary and structural
      analyses (A-, B- and C-families), with the B- and C-families evolving after the A
      family. The A-family utilizes two proton input channels to transfer protons for
      pumping and chemistry, whereas the B- and C-families require only one. Generally,
      the B- and C-families also have higher apparent oxygen affinities than the A
      family. Here we use whole cell proton pumping measurements to demonstrate
      differential proton pumping efficiencies between representatives of the A-, B-,
      and C-oxygen reductase families. The A-family has a coupling stoichiometry of 1
      H(+)/e(-), whereas the B- and C-families have coupling stoichiometries of 0.5
      H(+)/e(-). The differential proton pumping stoichiometries, along with
      differences in the structures of the proton-conducting channels, place critical
      constraints on models of the mechanism of proton pumping. Most significantly, it
      is proposed that the adaptation of aerobic respiration to low oxygen environments
      resulted in a concomitant reduction in energy conservation efficiency, with
      important physiological and ecological consequences.

PMID- 21844376
TI  - Sensing membrane stress with near IR-emissive porphyrins.
AB  - Probes embedded within a structure can enable prediction of material behavior or
      failure. Carefully assembled composites that respond intelligently to physical
      changes within a material could be useful as intrinsic sensors. Molecular rotors
      are one such tool that can respond optically to physical environmental changes.
      Here, we propose to use molecular rotors within a polymersome membrane to report
      membrane stress. Using supermolecular porphyrin-based fluorophores as rotors, we
      characterize changes in the optical emission of these near-infrared (NIR)
      emissive probes embedded within the hydrophobic core of the polymersome membrane.
      The configuration of entrapped fluorophore depends on the available space within
      the membrane; in response to increased volume, emission is blue shifted. We used
      this feature to study how shifts in fluorescence correlate to membrane integrity,
      imparted by membrane stress. We monitored changes in emission of these porphyrin
      based fluorophores resulting from membrane stress produced through a range of
      physical and chemical perturbations, including surfactant-induced lysis,
      hydrolytic lysis, thermal degradation, and applied stress by micropipette
      aspiration. This paper comprehensively illustrates the potential for
      supermolecular porphyrin-based fluorophores to detect intrinsic physical changes
      in a wide variety of environments, and suggests how molecular rotors may be used
      in soft materials science and biology as sensors.

PMID- 21844377
TI  - Mesopores provide an amorphous state suitable for studying biomolecular
      structures at cryogenic temperatures.
AB  - In nano-confinements, aqueous solutions can be found to remain in a liquid state
      at subfreezing temperatures. The finding provides a means of entering into
      previously inaccessible temperature regions for studying the dynamics and
      structure of bulk liquid. Here we show that studying biomolecular structures in
      nano-confinements improves the accuracy of cryostructures and provides better
      insight into the relationship between hydration water and biomolecules. Synthetic
      prion protein peptides are studied in two experimental conditions: (i) in
      confined nanochannels within mesoporous materials, and (ii) in vitrified bulk
      solvents, with a temperature range of 50-275 K, using cw/pulse ESR techniques. A
      large inhomogeneous lineshape broadening is only observed for the spectra from
      the vitrified bulk solvent below 70 K, suggesting a possible peptide clustering
      in the solution. The spin-counting and distance measurements by DEER-ESR provide
      further evidence that peptides are dispersed homogeneously in mesopores but
      heterogeneously in vitrified solvents wherein the biomolecular structure is
      disturbed due to heterogeneity in the bulk solvent structure. Our study
      demonstrates that the nanospace within mesoporous materials provides an amorphous
      environment that is better than vitrified bulk solvent for studying biostructures
      at cryogenic temperatures.

PMID- 21844378
TI  - Innate C-H trifluoromethylation of heterocycles.
AB  - Direct methods for the trifluoromethylation of heteroaromatic systems are in
      extremely high demand in nearly every sector of chemical industry. Here we report
      the discovery of a general procedure using a benchtop stable trifluoromethyl
      radical source that functions broadly on a variety of electron deficient and rich
      heteroaromatic systems and demonstrates high functional group tolerance. This C-H
      trifluoromethylation protocol is operationally simple (avoids gaseous CF(3)I),
      scalable, proceeds at ambient temperature, can be used directly on unprotected
      molecules, and is demonstrated to proceed at the innately reactive positions of
      the substrate. The unique and orthogonal reactivity of the trifluoromethyl
      radical relative to aryl radicals has also been investigated on both a complex
      natural product and a pharmaceutical agent. Finally, preliminary data suggest
      that the regioselectivity of C-H trifluoromethylation can be fine-tuned simply by
      judicious solvent choice.

PMID- 21844379
TI  - Reversibility and efficiency in electrocatalytic energy conversion and lessons
      from enzymes.
AB  - Enzymes are long established as extremely efficient catalysts. Here, we show that
      enzymes can also be extremely efficient electrocatalysts (catalysts of redox
      reactions at electrodes). Despite being large and electronically insulating
      through most of their volume, some enzymes, when attached to an electrode,
      catalyze electrochemical reactions that are otherwise extremely sluggish (even
      with the best synthetic catalysts) and require a large overpotential to achieve a
      useful rate. These enzymes produce high electrocatalytic currents, displayed in
      single bidirectional voltammetric waves that switch direction (between oxidation
      and reduction) sharply at the equilibrium potential for the substrate redox
      couple. Notoriously irreversible processes such as CO(2) reduction are thereby
      rendered electrochemically reversible--a consequence of molecular evolution
      responding to stringent biological drivers for thermodynamic efficiency. Enzymes
      thus set high standards for the catalysts of future energy technologies.

PMID- 21844380
TI  - Nucleic acid-binding polymers as anti-inflammatory agents.
AB  - Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can
      be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll
      like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs
      can engender a variety of inflammatory and autoimmune diseases. The redundancy of
      the TLR family encouraged us to seek materials that can neutralize the
      proinflammatory effects of any nucleic acid regardless of its sequence, structure
      or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers
      can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether
      they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic
      administration of such polymers can prevent fatal liver injury engendered by
      proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore
      these polymers represent a novel class of anti-inflammatory agent that can act as
      molecular scavengers to neutralize the proinflammatory effects of various nucleic
      acids.

PMID- 21844381
TI  - Creating compact comparative health care information: what are the key quality
      attributes to present for cataract and total hip or knee replacement surgery?
AB  - BACKGROUND: The recent emphasis on providing comparative health care data to the
      public has resulted in a large amount of online information. To focus on the most
      essential attributes, insight is needed into which attributes are actually
      considered by consumers. OBJECTIVE: To assess which attributes of Dutch hospital
      performance information contribute most to consumers' hospital choice for
      cataract and total hip or knee replacement surgery. DESIGN: Two discrete-choice
      experiments were performed: one for cataract surgery and one for total hip or
      knee replacement surgery. Participants viewed hypothetical hospitals based on
      representative values for 10 attributes (e.g., distance to the hospital, waiting
      time for the surgery, conduct of professionals, information provision,
      complication rate) and were asked to select the hospital they would choose if
      they needed treatment. We used multilevel logistic regression analysis to test
      the effects of the attributes and the interactions between attributes and
      respondent characteristics on consumers' hospital choice. RESULTS: All except one
      attribute (length of the first appointment with the ophthalmologist) contributed
      significantly to consumers' choices. Although some differences were found between
      cataract and hip/knee replacement surgery, the most influential attributes for
      both types of surgeries were distance, waiting time, and the attributes of
      patient safety (complication rate of capsular rupture and the use of procedures
      to prevent adverse effects of thrombosis). Interaction effects were found between
      hospital attributes, on one hand, and age, education, and consumer choice
      orientation, on the other hand. CONCLUSIONS: As for cataract and total hip/knee
      replacement surgery, the attributes that seem most important to consumers when
      choosing a hospital are access (waiting time and distance) and patient safety
      attributes.

PMID- 21844382
TI  - Functional gap junctions accumulate at the immunological synapse and contribute
      to T cell activation.
AB  - Gap junction (GJ) mediates intercellular communication through linked
      hemichannels from each of two adjacent cells. Using human and mouse models, we
      show that connexin 43 (Cx43), the main GJ protein in the immune system, was
      recruited to the immunological synapse during T cell priming as both GJs and
      stand-alone hemichannels. Cx43 accumulation at the synapse was Ag specific and
      time dependent, and required an intact actin cytoskeleton. Fluorescence recovery
      after photobleaching and Cx43-specific inhibitors were used to prove that
      intercellular communication between T cells and dendritic cells is bidirectional
      and specifically mediated by Cx43. Moreover, this intercellular cross talk
      contributed to T cell activation as silencing of Cx43 with an antisense or
      inhibition of GJ docking impaired intracellular Ca(2+) responses and cytokine
      release by T cells. These findings identify Cx43 as an important functional
      component of the immunological synapse and reveal a crucial role for GJs and
      hemichannels as coordinators of the dendritic cell-T cell signaling machinery
      that regulates T cell activation.

PMID- 21844383
TI  - NKT cells are required for complete Freund's adjuvant-mediated protection from
      autoimmune diabetes.
AB  - Autoimmune diabetes in NOD mice can be prevented by application of Ags derived
      from Mycobacterium tuberculosis in the form of bacillus Calmette-Guerin or CFA.
      Disease protection by CFA is associated with a reduction in the numbers of
      pathogenic beta-cell specific, self-reactive CTLs, a phenomenon dependent on the
      presence and function of NK cells. However, the mechanisms by which NK cells are
      activated and recruited by heat-killed M. tuberculosis within CFA are unclear. In
      this study, we report that CFA-mediated NK cell activation and mobilization is
      dependent on CD1d expression. The administration of M. tuberculosis from CFA
      results in rapid NKT cell activation and IFN-gamma secretion both in vitro and in
      vivo. CFA-induced NKT cell activation is intact in MyD88(-/-) mice suggesting
      that the mechanism is independent of TLR signaling. Furthermore, CD1d expression
      was found to be essential for both M. tuberculosis-triggered NKT cell activation
      and CFA-mediated protection of NOD mice from diabetes. Collectively, these
      findings reveal hitherto previously unidentified roles for NKT cells in the
      adjuvant-promoting effects of CFA on innate and adaptive immunity.

PMID- 21844384
TI  - Differential regulation of proximal and distal Vbeta segments upstream of a
      functional VDJbeta1 rearrangement upon beta-selection.
AB  - Developmental stage-specific regulation of transcriptional accessibility helps
      control V(D)J recombination. Vbeta segments on unrearranged TCRbeta alleles are
      accessible in CD4(-)/CD8(-) (double-negative [DN]) thymocytes, when they
      recombine, and inaccessible in CD4(+)/CD8(+) (double-positive [DP]) thymocytes,
      when they do not rearrange. Downregulation of Vbeta accessibility on unrearranged
      alleles is linked with Lat-dependent beta-selection signals that inhibit Vbeta
      rearrangement, stimulate Ccnd3-driven proliferation, and promote DN-to-DP
      differentiation. Transcription and recombination of Vbetas on VDJbeta-rearranged
      alleles in DN cells has not been studied; Vbetas upstream of functional VDJbeta
      rearrangements have been found to remain accessible, yet not recombine, in DP
      cells. To elucidate contributions of beta-selection signals in regulating Vbeta
      transcription and recombination on VDJbeta-rearranged alleles, we analyzed wild
      type, Ccnd3(-/-), and Lat(-/-) mice containing a preassembled functional
      Vbeta1DJCbeta1 (Vbeta1(NT)) gene. Vbeta10 segments located just upstream of this
      VDJCbeta1 gene were the predominant germline Vbetas that rearranged in
      Vbeta1(NT/NT) and Vbeta1(NT/NT)Ccnd3(-/-) thymocytes, whereas Vbeta4 and Vbeta16
      segments located further upstream rearranged at similar levels as Vbeta10 in
      Vbeta1(NT/NT)Lat(-/-) DN cells. We previously showed that Vbeta4 and Vbeta16, but
      not Vbeta10, are transcribed on Vbeta1(NT) alleles in DP thymocytes; we now
      demonstrate that Vbeta4, Vbeta16, and Vbeta10 are transcribed at similar levels
      in Vbeta1(NT/NT)Lat(-/-) DN cells. These observations indicate that suppression
      of Vbeta rearrangements is not dependent on Ccnd3-driven proliferation, and DN
      residence can influence the repertoire of Vbetas that recombine on alleles
      containing an assembled VDJCbeta1 gene. Our findings also reveal that beta
      selection can differentially silence rearrangement of germline Vbeta segments
      located proximal and distal to functional VDJbeta genes.

PMID- 21844385
TI  - Aryl hydrocarbon receptor is critical for homeostasis of invariant gammadelta T
      cells in the murine epidermis.
AB  - An immunoregulatory role of aryl hydrocarbon receptor (AhR) has been shown in
      conventional alphabeta and gammadelta T cells, but its function in skin
      gammadelta T cells (dendritic epidermal T cells [DETC]) is unknown. In this
      study, we demonstrate that DETC express AhR in wild-type mice, and are
      specifically absent in the epidermis of AhR-deficient mice (AhR-KO). We show that
      DETC precursors are generated in the thymus and home to the skin. Proliferation
      of DETC in the skin was impaired in AhR-KO mice, resulting in a >90% loss
      compared with wild type. Surprisingly, DETC were not replaced by alphabeta T
      cells or conventional gammadelta T cells, suggesting a limited time frame for
      seeding this niche. We found that DETC from AhR-KO mice failed to express the
      receptor tyrosine kinase c-Kit, a known growth factor for gammadelta T cells in
      the gut. Moreover, we found that c-kit is a direct target of AhR, and propose
      that AhR-dependent c-Kit expression is potentially involved in DETC homeostasis.
      DETC are a major source of GM-CSF in the skin. Recently, we had shown that
      impaired Langerhans cell maturation in AhR-KO is related to low GM-CSF levels.
      Our findings suggest that the DETCs are necessary for LC maturation, and provide
      insights into a novel role for AhR in the maintenance of skin-specific gammadelta
      T cells, and its consequences for the skin immune network.

PMID- 21844386
TI  - Nephrotic syndrome and subepithelial deposits in a mouse model of immune-mediated
      anti-podocyte glomerulonephritis.
AB  - Subepithelial immune complex deposition in glomerular disease causes local
      inflammation and proteinuria by podocyte disruption. A rat model of membranous
      nephropathy, the passive Heymann nephritis, suggests that Abs against specific
      podocyte Ags cause subepithelial deposit formation and podocyte foot process
      disruption. In this study, we present a mouse model in which a polyclonal sheep
      anti-mouse podocyte Ab caused subepithelial immune complex formation. Mice
      developed a nephrotic syndrome with severe edema, proteinuria, hypoalbuminemia,
      and elevated cholesterol and triglycerides. Development of proteinuria was
      biphasic: an initial protein loss was followed by a second massive increase of
      protein loss beginning at approximately day 10. By histology, podocytes were
      swollen. Electron microscopy revealed 60-80% podocyte foot process effacement and
      subepithelial deposits, but no disruption of the glomerular basement membrane.
      Nephrin and synaptopodin staining was severely disrupted, and podocyte number was
      reduced in anti-podocyte serum-treated mice, indicating severe podocyte damage.
      Immunohistochemistry detected the injected anti-podocyte Ab exclusively along the
      glomerular filtration barrier. Immunoelectron microscopy localized the Ab to
      podocyte foot processes and the glomerular basement membrane. Similarly,
      immunohistochemistry localized mouse IgG to the subepithelial space. The third
      complement component (C3) was detected in a linear staining pattern along the
      glomerular basement membrane and in the mesangial hinge region. However, C3
      deficient mice were not protected from podocyte damage, indicating a complement
      independent mechanism. Twenty proteins were identified as possible Ags to the
      sheep anti-podocyte serum by mass spectrometry. Together, these data establish a
      reproducible model of immune-mediated podocyte injury in mice with subepithelial
      immune complex formation.

PMID- 21844388
TI  - Development and function of innate polyclonal TCRalphabeta+ CD8+ thymocytes.
AB  - Innate CD8 T cells are found in mutant mouse models, but whether they are
      produced in a normal thymus remains controversial. Using the RAG2p-GFP mouse
      model, we found that ~10% of TCRalphabeta(+) CD4(-)CD8(+) thymocytes were innate
      polyclonal T cells (GFP(+)CD44(hi)). Relative to conventional T cells, innate CD8
      thymocytes displayed increased cell surface amounts of B7-H1, CD2, CD5, CD38, IL
      2Rbeta, and IL-4Ralpha and downmodulation of TCRbeta. Moreover, they
      overexpressed several transcripts, including T-bet, Id3, Klf2, and, most of all,
      Eomes. Innate CD8 thymocytes were positively selected, mainly by nonhematopoietic
      MHCIa(+) cells. They rapidly produced high levels of IFN-gamma upon stimulation
      and readily proliferated in response to IL-2 and IL-4. Furthermore, low numbers
      of innate CD8 thymocytes were sufficient to help conventional CD8 T cells expand
      and secrete cytokine following Ag recognition. This helper effect depended on
      CD44-mediated interactions between innate and conventional CD8 T cells. We
      concluded that innate TCRalphabeta(+) CD8 T cells represent a sizeable proportion
      of normal thymocytes whose development and function differ in many ways from
      those of conventional CD8 T cells.

PMID- 21844389
TI  - Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced
      activation in human monocyte-derived dendritic cells.
AB  - Dendritic cells (DCs) are key players in initiating and directing the immune
      response. Therefore, their activation state and functional differentiation need
      to be tightly controlled. The activating stimuli and their signaling networks
      have long been an area of focus in DC research. Recent investigations have also
      shed light on the mechanisms of counterregulation and fine-tuning of DC
      functions. One class of proteins involved in these processes is the family of
      suppressors of cytokine signaling (SOCS), whose members were originally described
      as feedback inhibitors of cytokine-induced JAK/STAT signaling. Essential roles in
      DC function have been assigned to SOCS1 and SOCS3. In this article, we show that
      SOCS2 also is involved in DC regulation. In human and in murine DCs, SOCS2 is a
      highly TLR-responsive gene, which is expressed in a time-delayed fashion
      beginning 8 h after TLR ligation. Functionally, silencing of SOCS2 in DCs results
      in hyperphosphorylation of STAT3 at later time points. As a consequence, SOCS2
      deficient DCs secrete increased amounts of the cytokines IL-1beta and IL-10, both
      being transcriptional targets of STAT3. We propose a model in which SOCS2 acts as
      a negative regulator of TLR-induced DC activation. The delayed expression of
      SOCS2 provides a mechanism of late-phase counterregulation and limitation of
      inflammation-driving DC activity.

PMID- 21844387
TI  - CpG and non-CpG oligodeoxynucleotides directly costimulate mouse and human CD4+ T
      cells through a TLR9- and MyD88-independent mechanism.
AB  - TLR ligands are known to activate APCs, but direct T cell responsiveness to TLR
      ligands is controversial. Because of their clinical relevance, we performed in
      depth studies of the effects of the TLR9-associated ligands,
      oligodeoxynucleotides (ODNs), on highly purified T lymphocytes. Both CpG and non
      CpG ODNs directly costimulate mouse and human CD4(+) T cells, resulting in
      activation marker upregulation, cytokine secretion, elevated TCR phosphorylation,
      and proliferation. Surprisingly, ODN costimulation occurred independently of TLR9
      and MyD88, as well as ICOS, CD28, and TRIF. TLR9-antagonist ODNs likewise
      promoted T cell activation, which has important implications for the study of
      these "inhibitory" ODNs in inflammatory diseases. Cytokine profiling revealed
      that ODNs promote polarization of distinct Th subsets, and that ODNs
      differentially affect human naive and memory T cells. Our studies reveal a
      striking and unexpected ability of ODNs to directly activate and polarize T
      cells, presenting an opportunity to enhance the paradigm for selection of
      therapeutic ODNs in humans.

PMID- 21844390
TI  - Multiple CD4+ T cell subsets produce immunomodulatory IL-10 during respiratory
      syncytial virus infection.
AB  - The host immune response is believed to contribute to the severity of pulmonary
      disease induced by acute respiratory syncytial virus (RSV) infection. Because RSV
      induced pulmonary disease is associated with immunopathology, we evaluated the
      role of IL-10 in modulating the RSV-specific immune response. We found that IL-10
      protein levels in the lung were increased following acute RSV infection, with
      maximum production corresponding to the peak of the virus-specific T cell
      response. The majority of IL-10-producing cells in the lung during acute RSV
      infection were CD4(+) T cells. The IL-10-producing CD4(+) T cells included
      Foxp3(+) regulatory T cells, Foxp3(-) CD4(+) T cells that coproduce IFN-gamma,
      and Foxp3(-) CD4(+) T cells that do not coproduce IFN-gamma. RSV infection of IL
      10-deficient mice resulted in more severe disease, as measured by increased
      weight loss and airway resistance, as compared with control mice. We also
      observed an increase in the magnitude of the RSV-induced CD8(+) and CD4(+) T cell
      response that correlated with increased disease severity in the absence of IL-10
      or following IL-10R blockade. Interestingly, IL-10R blockade during acute RSV
      infection altered CD4(+) T cell subset distribution, resulting in a significant
      increase in IL-17A-producing CD4(+) T cells and a concomitant decrease in
      Foxp3(+) regulatory T cells. These results demonstrate that IL-10 plays a
      critical role in modulating the adaptive immune response to RSV by limiting T
      cell-mediated pulmonary inflammation and injury.

PMID- 21844391
TI  - IL-12p35 subunit contributes to autoimmunity by limiting IL-27-driven regulatory
      responses.
AB  - Contrasting results have emerged from studies performed using IL-12p35(-/-) mice.
      Animals lacking the IL-12p35 subunit can either be protected from or develop
      exacerbated autoimmune diseases, intracellular infections, and delayed-type
      hypersensitivity responses. In this study, we report that mice lacking the IL
      12p35 subunit develop a significantly milder Ag-induced arthritis compared with
      wild-type (WT) mice. Lack of severe inflammation is accompanied by an increase in
      the mRNA levels of the Ebi-3 and p28 subunits and increased secretion of IL-27
      and IL-10. This anti-inflammatory environment contributed to increased
      differentiation of regulatory T and B cells with intact suppressive function.
      Furthermore, IL-12p35(-/-) mice display reduced numbers of Th17 cells compared
      with WT arthritic mice. Neutralization of IL-27, but not the systemic
      administration of IL-12, restored inflammation and Th17 to levels seen in WT
      mice. The restoration of disease phenotype after anti-IL-27 administration
      indicates that the IL-12p35 subunit acts as negative regulator of the developing
      IL-27 response in this model of arthritis.

PMID- 21844392
TI  - HIV-DNA priming alters T cell responses to HIV-adenovirus vaccine even when
      responses to DNA are undetectable.
AB  - Many candidate HIV vaccines are designed to primarily elicit T cell responses.
      Although repeated immunization with the same vaccine boosts Ab responses, the
      benefit for T cell responses is ill defined. We compared two immunization
      regimens that include the same recombinant adenoviral serotype 5 (rAd5) boost.
      Repeated homologous rAd5 immunization fails to increase T cell responses, but
      increases gp140 Ab responses 10-fold. DNA prime, as compared with rAd5 prime,
      directs long-term memory CD8(+) T cells toward a terminally differentiated
      effector memory phenotype with cytotoxic potential. Based on the kinetics of
      activated cells measured directly ex vivo, the DNA vaccination primes for both
      CD4(+) and CD8(+) T cells, despite the lack of detection of the latter until
      after the boost. These results suggest that heterologous prime-boost combinations
      have distinct immunological advantages over homologous prime-boosts and suggest
      that the effect of DNA on subsequent boosting may not be easily detectable
      directly after the DNA vaccination.

PMID- 21844393
TI  - NLRP3/caspase-1-independent IL-1beta production mediates diesel exhaust particle
      induced pulmonary inflammation.
AB  - Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in
      the lung; however, the mechanisms are largely unclear. IL-1beta/IL-1RI signaling
      is crucial in several lung inflammatory responses. Typically, caspase-1 is
      activated within the NLRP3 inflammasome that recognizes several damage-associated
      molecular patterns, which results in cleavage of pro-IL-1beta into mature IL
      1beta. In this study, we hypothesized that the NLRP3/caspase-1/IL-1beta pathway
      is critical in DEP-induced lung inflammation. Upon DEP exposure, IL-1RI knockout
      mice had reduced pulmonary inflammation compared with wild-type mice. Similarly,
      treatment with rIL-1R antagonist (anakinra) and IL-1beta neutralization impaired
      the DEP-induced lung inflammatory response. Upon DEP exposure, NLRP3 and caspase
      1 knockout mice, however, showed similar IL-1beta levels and comparable pulmonary
      inflammation compared with wild-type mice. In conclusion, these data show that
      the DEP-induced pulmonary inflammation acts through the IL-1beta/IL-1RI axis. In
      addition, DEP initiates inflammation independent of the classical NLRP3/caspase-1
      pathway, suggesting that other proteases might be involved.

PMID- 21844394
TI  - Novel highly sensitive IL-10-beta-lactamase reporter mouse reveals cells of the
      innate immune system as a substantial source of IL-10 in vivo.
AB  - In this study, we report on a novel, highly sensitive IL-10 reporter mouse based
      on the reporter enzyme beta-lactamase and the fluorescence resonance energy
      transfer substrate coumarin-cephalosporin-fluorescein (4). In contrast to an IL
      10 reporter mouse model that we generated by using enhanced GFP as reporter and
      allowed tracking IL-10 expression only in T cells, the IL-10-beta-lactamase
      reporter (ITIB) mouse enables us to easily analyze and quantify IL-10 production
      at the single-cell level in all myeloid and lymphoid cell types. Furthermore, the
      ITIB mouse allows studying of the kinetics of IL-10 expression on a single-cell
      basis and provides a valuable tool for in vivo screening of cell type-specific IL
      10-modulating drugs. Remarkably, the ITIB mouse revealed that, although a
      significant portion of each myeloid and lymphoid cell type produces IL-10,
      macrophages represent the major IL-10 producer population in several organs of
      naive mice. Moreover, using the examples of bacterial infection and
      transplantable skin melanoma models, we demonstrate the exceptional applicability
      of the ITIB mouse for the identification of IL-10-producing cells during immune
      responses in vivo. In this study, we identified tumor-infiltrating F4/80(+)
      macrophages as the major source for IL-10 in B16-F10 melanoma in vivo. During
      systemic infection with Yersinia enterocolitica, although the proportion of IL
      10(+) cells increased in each myeloid and lymphoid cell type population,
      infiltrating CD11b(+)Ly6G(+) neutrophils represent a majority among IL-10
      producing cells at the site of infection. We conclude that cells of the innate
      immune system that are involved in immune homeostasis or immune responses are
      substantial sources of IL-10.

PMID- 21844396
TI  - EBI2 guides serial movements of activated B cells and ligand activity is
      detectable in lymphoid and nonlymphoid tissues.
AB  - EBV-induced gene 2 (EBI2) was recently shown to direct the delayed movement of
      activated B cells to interfollicular and outer follicular regions of secondary
      lymphoid organs and to be required for mounting a normal T-dependent Ab response.
      In this study, we show that EBI2 promotes an early wave of Ag-activated B cell
      migration to the outer follicle in mice. Later, when B cells have moved to the T
      zone in a CCR7-dependent manner, EBI2 helps distribute the cells along the B zone
      T zone boundary. Subsequent EBI2-dependent movement to the outer follicle
      coincides with CCR7 downregulation and is promoted by CD40 engagement. Using a
      bioassay, we identify a proteinase K-resistant, hydrophobic EBI2 ligand activity
      in lymphoid and nonlymphoid tissues. Production of EBI2 ligand activity by a cell
      line is sensitive to statins, suggesting production in a 3-hydroxy-3-methyl
      glutaryl-CoA reductase-dependent manner. CD40-activated B cells show sustained
      EBI2-dependent responsiveness to the bioactivity. These findings establish a role
      for EBI2 in helping control B cell position at multiple stages during the Ab
      response and they suggest that EBI2 responds to a broadly distributed lipid
      ligand.

PMID- 21844395
TI  - Separation of mutational and transcriptional enhancers in Ig genes.
AB  - Secondary Ig gene diversification relies on activation-induced cytidine deaminase
      (AID) to create U:G mismatches that are subsequently fixed by mutagenic repair
      pathways. AID activity is focused to Ig loci by cis-regulatory DNA sequences
      named targeting elements. In this study, we show that in contrast to prevailing
      thought in the field, the targeting elements in the chicken IGL locus are
      distinct from classical transcriptional enhancers. These mutational enhancer
      elements (MEEs) are required over and above transcription to recruit AID-mediated
      mutagenesis to Ig loci. We identified a small 222-bp fragment in the chicken IGL
      locus that enhances mutagenesis without boosting transcription, and this sequence
      represents a key component of an MEE. Lastly, MEEs are evolutionarily conserved
      among birds, both in sequence and function, and contain several highly conserved
      sequence modules that are likely involved in recruiting trans-acting targeting
      factors. We propose that MEEs represent a novel class of cis-regulatory elements
      for which the function is to control genomic integrity.

PMID- 21844397
TI  - Survey of high school students' perceptions about their iPod use, knowledge of
      hearing health, and need for education.
AB  - PURPOSE: High school students' knowledge about hearing health and their
      perceptions of how they use personal listening devices (PLDs) including iPods
      were surveyed to determine the need, content, and preferred format for
      educational outreach to them. METHOD: This study was a descriptive convenience
      survey of students at a California high school. An 83-item questionnaire was
      administered in December 2009 to assess students' demographics, knowledge of
      hearing health, perceived iPod use, and risk activities. RESULTS: The response
      rate was 56%. Most of the students perceived that they used iPods safely.
      However, responses indicated that many of the respondents could be at risk of
      injury to themselves or others if they became unaware of their surroundings while
      listening to iPods. Some students were knowledgeable about hearing health and
      safe iPod use, but most needed information about hearing loss and hearing
      conservation. CONCLUSION: Most of the students needed education (e.g., via health
      classes or the Internet) about hearing health, the warning signs of hearing loss,
      and how to prevent hearing loss. Resources for educational audiologists are
      provided.

PMID- 21844398
TI  - The interface of language proficiency and identity: a profile analysis of
      bilingual adolescents and their writing.
AB  - PURPOSE: The purpose of this study was to explore how adolescent English language
      learners' (ELLs') language and literacy experiences impacted their identities as
      bilingual writers. METHOD: Six students were randomly selected from a group of 20
      Spanish-speaking ELLs, ages 11-14, who participated in a larger, mixed-methods
      study on bilingual writing (see Danzak, 2011). The participants produced 10
      written journal entries in their language of choice (English, Spanish, or both)
      and were interviewed. Qualitative analyses were applied to the participants'
      writing and interviews, both individually and cross-case. Findings were
      integrated to some extent with the outcomes of quantitative measures applied to
      the students' writing. RESULTS: Three patterns emerged: ethnic differences,
      language discrimination, and language preference. Also, the students' self
      identification as monolingual or bilingual was reflected in their attitudes
      toward language learning and their outcomes on writing measures. Three portraits
      of emerging bilingual writers are discussed: struggling emerging, dominant
      emerging, and balanced emerging. Language and literacy learning strategies are
      recommended for each. CONCLUSIONS: Qualitative profiles of adolescent ELLs offer
      an understanding of students' experiences and identities that augments
      information provided by quantitative writing measures. Additionally, a mixed
      methods profile analysis may aid in the identification of adolescent ELLs who may
      be struggling with undiagnosed language learning disabilities.

PMID- 21844399
TI  - What is orthographic knowledge?
AB  - PURPOSE: Orthographic knowledge refers to the information that is stored in
      memory that tells us how to represent spoken language in written form.
      Unfortunately, terms used to talk about orthographic knowledge and the two
      individual components that contribute to it have varied widely in the literature.
      Thus, consensus on the term, its meaning, and the tasks used to assess
      orthographic knowledge is needed. METHOD: In this tutorial, the problems and
      inconsistencies in terms and tasks used to define and measure orthographic
      knowledge are reviewed, and suggestions for using specific terms are offered.
      Additionally, orthographic knowledge development, considerations of its role in
      literacy development, and its independence from other factors that contribute to
      literacy development are discussed. Finally, ideas for overcoming current
      obstacles in discussions of orthographic knowledge and suggestions for future
      research endeavors are offered. CONCLUSION: With consensus on what orthographic
      knowledge is and how it should be measured, practitioners should be better
      prepared for assessing orthographic knowledge and implementing instructional
      practices accordingly.

PMID- 21844401
TI  - Educational audiologists: their access, benefit, and collaborative assistance to
      speech-language pathologists in schools.
AB  - PURPOSE: The main goals of this study were to determine if school-based speech
      language pathologists (SLPs) have access to the services of an audiologist and if
      those SLPs felt they obtained benefit from the audiologist's services. Additional
      goals included gathering information about SLPs' (a) understanding of basic
      audiological concepts typical for a school setting, (b) added job
      responsibilities brought about by lack of access to an audiologist, and (c)
      collaboration with audiologists. METHOD: A 36-item survey was e-mailed to 1,000
      SLPs listed with the American Speech-Language-Hearing Association as being
      employed in schools. Two-hundred and nine respondents from 42 states returned the
      survey. RESULTS: Seventy-six percent of the responding SLPs had access at some
      time to an audiologist, with 88% of them believing they received benefit from the
      services provided by that audiologist, primarily in the areas of hearing
      screenings and in-services. Thirty-eight SLPs (58%) who did not have access to an
      audiologist reported having additional job responsibilities. CONCLUSION: Many
      school-based SLPs believed they received benefit from an audiologist when they
      had access to one. Collaboration between these professionals was strong, yet
      findings indicate that audiologists could improve their collaborative efforts
      with SLPs and assist them in working within their scope of practice and
      maintaining their ethical standards.

PMID- 21844400
TI  - Peer victimization among students with specific language impairment, attention
      deficit/hyperactivity disorder, and typical development.
AB  - PURPOSE: The potential contributions of behavioral and verbal liabilities to
      social risk were examined by comparing peer victimization levels in children with
      specific language impairment (SLI) to those in children with attention
      deficit/hyperactivity disorder (ADHD) and typically developing (TD) children.
      METHOD: Sixty children (age range: 7-8 years) participated in the study.
      Standardized verbal measures and parent ratings of behavioral difficulties were
      combined with children's self-reports of their school and peer environments to
      examine the risk for negative peer experiences associated with clinical status.
      RESULTS: Clinical status was associated with elevated levels of victimization,
      especially for participants with SLI. A potential buffering effect for number of
      close friendships was found for participants with ADHD and TD participants, but
      not for participants with SLI. Peer victimization was associated with elevated
      levels of hyperactivity and stronger narrative skills for participants with SLI.
      CONCLUSION: These results highlight the importance of peer victimization in the
      social adjustment of students with developmental language disorders.

PMID- 21844402
TI  - Do developmental communication disorders exist in the signed modality?
      Perspectives from professionals.
AB  - PURPOSE: This study focused on whether developmental communication disorders
      exist in American Sign Language (ASL) and how they might be characterized. ASL
      studies is an emerging field; educators and clinicians have minimal access to
      descriptions of communication disorders of the signed modality. Additionally,
      there are limited resources for assessing ASL acquisition. This article is
      designed to raise clinicians' awareness about developmental communication
      disorders in ASL and categorize types of atypicality that have been witnessed.
      METHOD: We conducted 4 focus groups and one 1-on-1 interview with a total of 22
      adults (7 Deaf, 15 hearing) who work at bilingual-bicultural (ASL-English)
      schools for the Deaf. Experiences of these educators and language professionals
      were analyzed qualitatively using a combination of grounded theory (Charmaz,
      2001; Strauss & Corbin, 1998) and a modified van Kaam approach (Moustakas, 1994).
      RESULTS: Participants confirmed observations of children with suspected
      communication disorders and considered the prevalence, possible etiologies, and
      psychosocial aspects of such disorders in ASL. They reported frustration at the
      lack of diagnostic tools for reliable identification and intervention strategies
      to be used in educational settings. CONCLUSION: This work provides us with
      practitioner accounts proving that developmental communication disorders do exist
      in ASL. Future reports will describe primary data from signers with atypical
      language attributes.

PMID- 21844403
TI  - Classification accuracy of brief parent report measures of language development
      in Spanish-speaking toddlers.
AB  - PURPOSE: The purpose of the current study was to examine the concurrent validity
      and classification accuracy of 3 parent report measures of language development
      in Spanish-speaking toddlers. METHOD: Forty-five Spanish-speaking parents and
      their 2-year-old children participated. Twenty-three children had expressive
      language delays (ELDs) as determined through multiple sources of information, and
      22 had typical language development (TD). Parents completed the Spanish version
      of the Ages and Stages Questionnaire (Spanish ASQ; Squires, Potter, & Bricker,
      1999) and the short-form of the Inventarios del Desarrollo de Habilidades
      Comunicativas Palabras y Enunciados (INV-II; Jackson-Maldonado, Bates, & Thal,
      1992; Jackson-Maldonado et al., 2003), which is the Spanish version of the
      MacArthur-Bates Communicative Development Inventories Words and Sentences form,
      and reported children's 3 longest utterances (M3L-W). Children were administered
      the Preschool Language Scale, Fourth Edition, Spanish Edition (SPLS-4; Zimmerman,
      Steiner, & Pond, 2002) at early childhood centers. RESULTS: All 3 parent report
      measures were significantly correlated with the SPLS-4, establishing their
      concurrent validity. Children with ELDs scored significantly lower than TD
      children on all 3 parent report measures. The Spanish ASQ demonstrated less than
      desirable levels of sensitivity and specificity; both the short-form INV-II and
      M3L-W measures demonstrated favorable sensitivity and specificity. Of these
      measures, M3L-W demonstrated the strongest classification accuracy qualities,
      including sensitivity, negative predictive value, and area under the receiver
      operating characteristics curve. CONCLUSION: The short-form INV-II and M3L-W
      demonstrated highly satisfactory classification accuracy of ELDs, but M3L-W
      demonstrated slightly stronger accuracy. These results indicate that these
      measures may be useful in screening for ELDs in Spanish-speaking toddlers.

PMID- 21844404
TI  - Improving the predictive accuracy of Static-99 and Static-2002 with older sex
      offenders: revised age weights.
AB  - Actuarial risk assessment scales and their associated recidivism estimates are
      generally developed on samples of offenders whose average age is well below 50
      years. Criminal behavior of all types declines with age; consequently, actuarial
      scales tend to overestimate recidivism for older offenders. The current study
      aimed to develop a revised scoring system for two risk assessment tools (Static
      99 and Static-2002) that would more accurately describe older offenders' risk of
      recidivism. Using data from 8,390 sex offenders derived from 24 separate samples,
      age was found to add incremental predictive validity to both Static-99 and Static
      2002. After creating new age weights, the resulting instruments (Static-99R and
      Static-2002R) had only slightly higher relative predictive accuracy. The absolute
      recidivism estimates, however, provided a substantially better fit for older
      offenders than the recidivism estimates from the original scales. We encourage
      evaluators to adopt the revised scales with the new age weights.

PMID- 21844405
TI  - Effect of recurrent laryngeal nerve identification technique in thyroidectomy on
      recurrent laryngeal nerve paralysis and hypoparathyroidism.
AB  - OBJECTIVE: To investigate whether the recurrent laryngeal nerve (RLN)
      identification technique used in thyroidectomy affects RLN paralysis and
      hypoparathyroidism. DESIGN: Patients were allocated into 2 groups according to
      the thyroidectomy technique used to identify the RLN: (1) superior-inferior
      direction, exploring the nerve where it enters the larynx, followed by superior
      pedicle ligation; and (2) inferior-superior direction, following the inferior
      pedicle ligation and identifying the nerve in the tracheoesophageal groove. The
      first and second groups included 67 and 128 patients, respectively. In the first
      group, 19 patients underwent lobo-isthmectomy, and 48 underwent total
      thyroidectomy. In the second group, 42 patients underwent lobo-isthmectomy, and
      86 underwent total thyroidectomy. We performed 115 and 214 RLN dissections in the
      first and second groups, respectively. SETTING: Academic tertiary hospital.
      PATIENTS: The study included 195 consecutive patients, 161 female (82.5%), and 34
      male (17.5%), who underwent thyroidectomy for goiter between January 2006 and
      August 2009. Their mean age was 44.7 years (range, 14-79 years). The mean follow
      up was 26 months (range, 12-42 months). INTERVENTIONS: Unilateral or bilateral
      total thyroidectomies performed using extracapsular dissection with 2 different
      RLN identification techniques. MAIN OUTCOME MEASURES: Incidence of hypocalcemia,
      vocal cord paralysis, hemorrhage, and wound infection. RESULTS: No RLN paralysis
      was observed in the first group. In the second group, unilateral RLN paralysis
      was seen in 2 of 128 patients (1.5%). Groups 1 and 2 included 48 and 86 total
      thyroidectomies, respectively. Temporary hypoparathyroidism was observed in 4
      patients in the first group (8.3%). In the second group, permanent
      hypoparathyroidism was observed only in 4 patients (4.6%), and temporary
      hypoparathyroidism was observed in 14 patients (16.2%). CONCLUSIONS: Comparing
      the 2 groups based on the frequencies of RLN paralysis and hypoparathyroidism, we
      found that complications were significantly lower in the first group (P < .05) in
      terms of hypoparathyroidism. The rate of hypoparathyroidism was significantly
      lower in the thyroidectomies that located the RLN using the superior-inferior
      approach. In our hands, the superior-inferior approach was a safer technique, in
      terms of avoiding complications.

PMID- 21844406
TI  - Endoscopic-assisted gland-preserving therapy for chronic sialadenitis: a German
      and US comparison.
AB  - OBJECTIVE: To determine whether unique patterns of care are evolving in the
      United States compared with Germany in endoscopic management of chronic
      sialadenitis. DESIGN: Comparison of consecutive series of patients. SETTING:
      Academic tertiary salivary referral centers in Germany and the United States.
      PATIENTS: A total of 446 patients having chronic sialadenitis treated with
      salivary endoscopy. MAIN OUTCOME MEASURES: To compare practice patterns and
      outcomes at each location, databases tracking patients having chronic
      sialadenitis treated with salivary endoscopy were searched for the following
      variables: age, sex, involved gland, radiographic studies, endoscopic findings,
      endoscopic-related complications, gland preservation rate, patient symptom
      control, and techniques for managing salivary stones and intraductal scar tissue.
      RESULTS: Significantly more patients in the US cohort had chronic sialadenitis of
      the parotid gland (P = .03) and multiple gland involvement (P < .001). Salivary
      endoscopy was regularly performed using local anesthesia in Germany and using
      general anesthesia in the United States (P < .001). Endoscopic-related
      complication rates were higher (10.9% vs 1.6%) and gland preservation rates lower
      (85.9% vs 98.4%) among US patients; however, patients with intact glands
      demonstrated similar rates of symptom control at both centers (92.7% in the
      United States vs 85.3% in Germany) at the last follow-up visit. The lower rate of
      gland preservation in the United States is largely because of lack of access to
      lithotripsy for larger salivary stones. CONCLUSIONS: Different patterns of care
      are emerging in the endoscopic management of chronic sialadenitis in the United
      States compared with Germany, where these techniques were largely developed.
      Nevertheless, patients with chronic sialadenitis at both locations who undergo
      endoscopic gland-preserving therapy have high rates of gland preservation and
      symptom control.

PMID- 21844407
TI  - Online script concordance test for clinical reasoning assessment in
      otorhinolaryngology: the association between performance and clinical experience.
AB  - OBJECTIVE: To report on the creation and administration of an online Script
      Concordance Test (SCT) for ear, nose, and throat (ENT), the ENT-SCT. DESIGN:
      Prospective study. SETTING: Two tertiary care university centers. PARTICIPANTS:
      In total, 132 individuals were asked to test an ENT-SCT of 20 cases and 94
      questions based on the major educational objectives of the ENT residency program.
      MAIN OUTCOME MEASURES: Three levels of experience were tested: medical students,
      ENT residents, and board-certified otorhinolaryngologists as the expert panel.
      The test's construct validity-whether scores were related to clinical experience
      was statistically analyzed. Reliability was estimated by the Cronbach alpha
      internal consistency coefficient. Participants' perception of the test was
      assessed with the use of a questionnaire. RESULTS: The 65 respondents with usable
      data were medical students (n = 21), ENT residents (n = 22), and experts (n =
      22). Total mean (SD) test scores differed significantly: 76.81 (3.31) for the
      expert panel, 69.05 (4.35) for residents, and 58.29 (5.86) for students. The
      Cronbach alpha coefficient was 0.95. More than two-thirds of the participants
      found the test to be realistic and relevant for assessing clinical reasoning. The
      test was also considered fun, interesting, and intuitive. CONCLUSIONS: The Web
      based ENT-SCT is feasible, reliable, and useful for assessing clinical reasoning.
      This online assessment tool may have applications for residency programs and
      continuing medical education.

PMID- 21844408
TI  - Familial clustering of hemangiomas.
AB  - OBJECTIVES: To assess the degree of relationship among individuals with
      hemangiomas and to evaluate the relative risk (RR) for family members of
      individuals with hemangiomas. DESIGN: Retrospective case-control study. SETTING:
      Utah Population Database. PARTICIPANTS: Data sets of individuals of different
      ages with International Classification of Diseases, Ninth Revision (ICD-9) codes
      for hemangiomas were created from sources having medical records linked to the
      Utah Population Database. Controls were selected who matched cases for sex, birth
      year, and birthplace inside vs outside of Utah. Ten controls were selected per
      case, and sampling was performed without replacement. Kinship analysis tools were
      used to identify pedigrees having excess individuals with hemangiomas. MAIN
      OUTCOME MEASURE: Using conditional logistic regression analysis, RR for
      hemangiomas among several kinship classes was determined. RESULTS: Identified
      were 2514 distinct cases 12 years or younger with ICD-9 code 228.01, and the RR
      for sibs in this group was significantly increased (RR, 2.52; P < .001). Seventy
      three founder families had 5 or more affected descendants with cluster P values
      <= .01; familial standardized incidence ratios ranged from 1.64 to 9.50. Family
      sizes ranged from 546 to 22 291 descendants. CONCLUSIONS: Sibs have increased RR
      for infantile hemangiomas, suggesting a potential genetic contribution to this
      likely multifactorial disease. Identification of large families with distantly
      related individuals will be helpful for future shared segment identification
      analyses.

PMID- 21844409
TI  - Outcomes of sphincter pharyngoplasty and palatal lengthening for velopharyngeal
      insufficiency: a 10-year experience.
AB  - OBJECTIVE: To report our experience in the care of patients treated for
      velopharyngeal insufficiency (VPI) with sphincter pharyngoplasty (SP) with or
      without the addition of palatal lengthening by Furlow palatoplasty (FP). DESIGN:
      Retrospective analysis. SETTING: Tertiary care cleft palate and craniofacial
      clinic. PATIENTS: Forty-six children with VPI, most of whom had palatal clefts,
      treated with SP (1998-2008). INTERVENTIONS: Treatment consisted of SP alone (n =
      20) or SP plus FP (n = 26). MAIN OUTCOME MEASURE: Rate of revision surgery,
      indicating persistent VPI after surgical treatment. RESULTS: Of 46 patients, 6
      (13%) required surgical revision. Regarding need for revision, no statistically
      significant differences were found concerning age, sex, cleft type, syndrome, or
      time between palate repair and SP. Indications for revision included persistent
      hypernasality (n = 2), inferior position (n = 2), flap dehiscence (n = 1), and
      obstructed sleep (n = 1). Postoperative improvement in velopharyngeal competence
      was documented in all revision cases. No patients required a second revision.
      Twenty-six of 46 patients (57%) underwent FP in addition to SP. The remaining 20
      patients (43%) had SP alone. The revision rate was 4% (n = 1) for the SP plus FP
      group and 25% (n = 5) for the SP alone group (P = .04). CONCLUSIONS: Sphincter
      pharyngoplasty is an effective procedure for the management of VPI, with a
      success rate of 87% when using need for surgical revision as the primary outcome
      measure. This number improved to 100% after a single revision, with elimination
      of VPI in all revision cases. Concomitant FP and SP may improve outcomes compared
      with SP alone. Further prospective studies are needed to elucidate this
      relationship.

PMID- 21844410
TI  - Orbital and periorbital infections: a national perspective.
AB  - OBJECTIVES: To describe the epidemiologic features of pediatric orbital and
      periorbital infections from a national perspective and to identify predictors of
      surgery. DESIGN: Analysis of the Kids' Inpatient Database. SETTING:
      Administrative data set. PATIENTS: Pediatric inpatient admissions with an
      International Classification of Diseases, Ninth Revision, Clinical Modification
      diagnosis of orbital cellulitis. MAIN OUTCOME MEASURES: Hospital admission,
      socioeconomic, and clinical variables were examined and predictors of surgical
      intervention were evaluated using logistic regression. RESULTS: A total 5440
      hospital admissions was noted for pediatric orbital cellulitis; of these, 672
      patients (12.4%) underwent surgical intervention. Mean length of stay for all
      patients was 3.8 days; 90.4% were routinely discharged. Patients who had surgery
      were older, with a mean (SE) age of 10.1 (0.29) years compared with 6.1 (0.10)
      years for nonsurgical patients (P < .001). Surgical patients had a significantly
      longer mean hospital stay (7.1 vs 3.4 days, P < .001) and a higher mean cost of
      care ($41 009 vs $13 008, P < .001) compared with nonsurgical patients.
      Demographic predictors of surgical intervention included male sex, admitting
      characteristics, and hospital location. Except for sex, these variables remained
      significant in a multivariate model. Clinically, diplopia is a predictor of
      surgical intervention (odds ratio, 6.3; 95% confidence interval, 3.4-11.7).
      CONCLUSIONS: This study describes the medical and surgical management of
      pediatric orbital and periorbital infections from a national perspective.
      Predictors of surgical intervention include older age, presentation with
      diplopia, and hospital admission via the emergency department. Knowledge of these
      variables facilitates analysis of resource utilization for pediatric orbital
      cellulitis and can be used to optimally triage patients, ultimately reducing
      costs and lengths of stay while preserving quality of care.

PMID- 21844411
TI  - Audiological profile of children and young adults with syndromic and complex
      craniosynostosis.
AB  - OBJECTIVES: To determine syndrome-specific type, severity, and prevalence of
      hearing loss to facilitate follow-up and treatment. DESIGN: Tertiary pediatric
      hospital craniofacial clinic survey study. If insufficient or no data were
      available for a child, he or she was referred to an audiologist for pure-tone
      audiometry. SETTING: Academic research facility. PATIENTS: Information was
      gathered regarding 132 children and young adults with craniosynostosis. MAIN
      OUTCOME MEASURES: The primary outcome was hearing assessment of children and
      young adults with various types of craniosynostosis. A secondary outcome was
      inference regarding the incidence of otitis media among children and young adults
      with craniosynostosis. RESULTS: We found mild or moderate hearing loss in 44.0%
      of patients with Apert syndrome, in 28.5% with Crouzon syndrome, in 62.1% with
      Muenke syndrome, in 28.6% with Saethre-Chotzen syndrome, and in 6.7% with complex
      craniosynostosis. Hearing loss was conductive in most patients with Apert,
      Crouzon, and Saethre-Chotzen syndromes and it was predominantly sensorineural in
      patients with Muenke syndrome. Sensorineural hearing loss at lower frequencies
      was found only in patients with Muenke syndrome. CONCLUSIONS: Most patients with
      syndromic and complex craniosynostosis have recurrent otitis media with effusion,
      causing episodes of conductive hearing loss throughout their lives. Sensorineural
      hearing loss can occur in all 4 syndromes studied but is the primary cause of
      hearing loss in children and young adults with Muenke syndrome. For patients with
      these syndromes, we recommend routine visits to the general practitioner or
      otolaryngologist, depending on national standards of care, to screen for otitis
      media with effusion throughout life. We also advise early screening for
      sensorineural hearing loss among children and young adults with these syndromes.

PMID- 21844412
TI  - Positional dependency in Asian patients with obstructive sleep apnea and its
      implication for hypertension.
AB  - OBJECTIVES: To investigate the relationship of obstructive sleep apnea (OSA) with
      positional dependency and to identify its clinical implication in an Asian
      population. DESIGN: Retrospective analysis. SETTING: Academic tertiary referral
      center. PATIENTS: A total of 1170 adults (1003 men and 167 women; mean [SD] age,
      50.8 [12.9] years) with OSA were included from February 1, 2004, through October
      31, 2008. INTERVENTION AND MAIN OUTCOME MEASURES: All patients underwent full
      night polysomnography. The anthropometric or polysomnographic variables between
      the patients with positional OSA (PPs) and those with nonpositional OSA (NPPs)
      were characterized, and multivariate analysis was performed to find the
      determining factors of positional dependency. The prevalence of hypertension was
      also investigated. RESULTS: Nearly 75% of the patients (874 [74.7%]) had
      positional dependency. Positional dependency was present in 87.0% of the patients
      with mild OSA (apnea hypopnea index [AHI], >=5 but <20), in 84.2% of those with
      moderate OSA (20 <= AHI < 40), and in 43.1% of those with severe OSA (AHI >= 40).
      The prevalence of PPs was 46.4% among severely obese patients (body mass index
      [BMI], >=30, calculated as weight in kilograms divided by height in meters
      squared) and 82.7% among the nonobese patients (BMI < 25) and 74.6% among obese
      patients (25 <= BMI <30). Multivariate analysis showed that the AHI was the most
      dominant variable that determined positional dependency, followed by the BMI. In
      the PP group, the percentages of deep sleep and rapid eye movement sleep were
      significantly greater compared with those in the NPP group. The Epworth
      Sleepiness Scale score was lower in the PP group. The prevalence of hypertension
      was 34.4% and 49.7% in the PP and NPP groups, respectively. CONCLUSIONS: This
      study demonstrates that the prevalence of PPs among Asians is almost three
      fourths of the patients and that the AHI is the most dominant factor for
      determining positional dependency, followed by BMI. The PP group had lower BMI, a
      lower AHI, longer deep sleep, longer rapid eye movement sleep, and less daytime
      sleepiness than did the NPPs. The prevalence of hypertension was also affected by
      positional dependency.

PMID- 21844413
TI  - Use of the modified SNOT-16 in primary care patients with clinically diagnosed
      acute rhinosinusitis.
AB  - OBJECTIVE: To determine the reliability, validity, responsiveness, and the
      minimal important difference (MID) for the Sinonasal Outcome Test-16 (SNOT-16) in
      the measurement of disease-specific quality of life (QOL) in adults with acute
      rhinosinusitis. STUDY DESIGN: Randomized controlled trial to evaluate antibiotic
      treatment for acute rhinosinusitis. SETTING: Ten community practices in St Louis,
      Missouri. METHODS: The modified SNOT-16 was completed at baseline (by both face
      to-face and telephone interviews) and by telephone interview at 3, 7, and 10 days
      by 166 adults with acute rhinosinusitis diagnosed clinically using standardized
      criteria (36% were male, 78% were white). Considering severity and frequency,
      patients rated how much they were bothered by each item using a 4-point scale.
      The mean SNOT-16 score (ranging from 0 [no problem] to 3 [large problem]) was
      compared with the patients' global assessment of change to evaluate
      responsiveness and the MID. RESULTS: The instrument was easy to use and took less
      than 5 minutes to complete. The SNOT-16 score identified statistically
      significant differences in the hypothesized direction for those reporting more or
      less severe symptoms (P = .02) and more or less bother (P < .001) demonstrating
      construct-related validity. The Cronbach alpha ranged from 0.82 to 0.91,
      demonstrating high internal consistency. There was a statistically significant
      decrease in scores with time (multivariate analysis of variance, P < .001). The
      effect sizes at days 3, 7, and 10 were 1.45, 2.34, and 2.90, respectively,
      indicating high sensitivity to clinical change. The MID was 0.5 units.
      CONCLUSION: The modified SNOT-16 is a valid instrument to assess effectiveness of
      interventions to improve disease-specific QOL in adults with acute
      rhinosinusitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00377403.

PMID- 21844414
TI  - The effect of indomethacin on paclitaxel sensitivity and apoptosis in oral
      squamous carcinoma cells: the role of nuclear factor-kappaB inhibition.
AB  - OBJECTIVE: To investigate new strategies to intensify chemosensitivity in head
      and neck squamous cell carcinoma. DESIGN: Oral squamous carcinoma cells were
      examined for nuclear factor-kappaB (NF-kappaB) activation and binding activity by
      paclitaxel, an agent currently used in head and neck cancer chemotherapy.
      Electromobility shift assays were used to assess the effect of indomethacin on NF
      kappaB binding activity. Cell proliferation assays were used to study cell
      sensitivity to paclitaxel. To examine whether cytotoxicity could be increased by
      specifically inhibiting NF-kappaB, a dominant negative cell line, inhibitor kappa
      B-alpha (IkappaBalpha), was stably expressed in CA-9-22 cells. RESULTS:
      Paclitaxel possessed the capacity to functionally activate NF-kappaB, as
      demonstrated by luciferase reporter gene assays and electromobility shift assay.
      Indomethacin was able to inhibit paclitaxel-mediated NF-kappaB activation and
      promote apoptosis of paclitaxel-treated cells at 24 hours. Indomethacin augmented
      the paclitaxel cell-killing effect. The dominant negative IkappaBalpha cell line
      exhibited increased chemosensitization to paclitaxel by 2- to 10-fold.
      CONCLUSIONS: Paclitaxel has the capacity to activate NF-kappaB in oral squamous
      carcinoma cells. Indomethacin can reverse this activation to decrease cell
      proliferation and increase apoptosis. Treatment strategies that combine
      paclitaxel with indomethacin may have therapeutic benefits attributable to
      paclitaxel chemosensitization through NF-kappaB inhibition.

PMID- 21844415
TI  - Current strategies in reconstruction of maxillectomy defects.
AB  - OBJECTIVE: To outline a contemporary review of defect classification and
      reconstructive options. DESIGN: Review article. SETTING: Tertiary care referral
      centers. RESULTS: Although prosthetic rehabilitation remains the standard of care
      in many institutions, the discomfort of wearing, removing, and cleaning a
      prosthesis; the inability to retain a prosthesis in large defects; and the
      frequent need for readjustments often limit the value of this cost-effective and
      successful method of restoring speech and mastication. However, flap
      reconstruction offers an option for many, although there is no agreement as to
      which techniques should be used for optimal reconstruction. Flap reconstruction
      also involves a longer recovery time with increased risk of surgical
      complications, has higher costs associated with the procedure, and requires
      access to a highly experienced surgeon. CONCLUSION: The surgeon and
      reconstructive team must make individualized decisions based on the extent of the
      maxillectomy defect (eg, the resection of the infraorbital rim, the extent of
      palate excision, skin compromise) and the need for radiation therapy.

PMID- 21844416
TI  - Histopathologic findings and clinical manifestations in a patient with dysphonia
      and vocal fold involvement by systemic sclerosis.

PMID- 21844417
TI  - Bilateral olfactory fossa respiratory epithelial adenomatoid hamartomas.

PMID- 21844419
TI  - Radiology quiz case 2. Keratocystic odontogenic tumor (KCOT).

PMID- 21844418
TI  - Radiology quiz case 1. Acute maxillary sinusitis secondary to a migrated dental
      implant obstructing the ostiomeatal complex.

PMID- 21844420
TI  - Radiology quiz case 3. Intralabyrinthine schwannomas (ILS).

PMID- 21844421
TI  - Pathology quiz case 1. Diffuse large B-cell lymphoma (DLBCL) of the thyroid.

PMID- 21844422
TI  - Pathology quiz case 2. Solitary fibrous tumor (SFT) of the hypopharynx.

PMID- 21844423
TI  - Pathology quiz case 3. Heterotopic gastric mucosa (inlet patch).

PMID- 21844424
TI  - Extent of thyroidectomy and survival in the SEER database: a case of citation
      amnesia.

PMID- 21844425
TI  - Eliminating preventable death on the battlefield.
AB  - OBJECTIVE: To evaluate battlefield survival in a novel command-directed casualty
      response system that comprehensively integrates Tactical Combat Casualty Care
      guidelines and a prehospital trauma registry. DESIGN: Analysis of battle injury
      data collected during combat deployments. SETTING: Afghanistan and Iraq from
      October 1, 2001, through March 31, 2010. PATIENTS: Casualties from the 75th
      Ranger Regiment, US Army Special Operations Command. MAIN OUTCOME MEASURES:
      Casualties were scrutinized for preventable adverse outcomes and opportunities to
      improve care. Comparisons were made with Department of Defense casualty data for
      the military as a whole. RESULTS: A total of 419 battle injury casualties were
      incurred during 7 years of continuous combat in Iraq and 8.5 years in
      Afghanistan. Despite higher casualty severity indicated by return-to-duty rates,
      the regiment's rates of 10.7% killed in action and 1.7% who died of wounds were
      lower than the Department of Defense rates of 16.4% and 5.8%, respectively, for
      the larger US military population (P = .04 and P = .02, respectively). Of 32
      fatalities incurred by the regiment, none died of wounds from infection, none
      were potentially survivable through additional prehospital medical intervention,
      and 1 was potentially survivable in the hospital setting. Substantial prehospital
      care was provided by nonmedical personnel. CONCLUSIONS: A command-directed
      casualty response system that trains all personnel in Tactical Combat Casualty
      Care and receives continuous feedback from prehospital trauma registry data
      facilitated Tactical Combat Casualty Care performance improvements centered on
      clinical outcomes that resulted in unprecedented reduction of killed-in-action
      deaths, casualties who died of wounds, and preventable combat death. This data
      driven approach is the model for improving prehospital trauma care and casualty
      outcomes on the battlefield and has considerable implications for civilian trauma
      systems.

PMID- 21844426
TI  - Vitamin D and nonmelanoma skin cancer in a health maintenance organization
      cohort.
AB  - OBJECTIVE: To examine the association of serum 25-hydroxyvitamin D (25-OHD) with
      the risk of nonmelanoma skin cancer (NMSC), defined as squamous cell carcinoma
      (SCC) and basal cell carcinoma (BCC). DESIGN: Cohort study. SETTING: Health
      maintenance organization. PATIENTS: The study included 3223 white health
      maintenance organization patients who sought osteoporosis- or low-bone-density
      related advice from 1997 to 2001. INTERVENTIONS: Vitamin D levels were
      ascertained at the time of the initial appointment, and a sufficient vitamin D
      level was defined as a baseline serum 25-OHD level greater than or equal to 30
      ng/mL (to convert to nanomoles per liter, multiply by 2.496) and as a deficient
      vitamin D level less than 15 ng/mL. MAIN OUTCOME MEASURES: The NMSC cases
      diagnosed between 1997 and 2009 were ascertained using claims data, considering
      first occurrence of specified disease outcome and complete person-years of follow
      up since baseline. Charts were abstracted for histologic subtype and anatomical
      location. RESULTS: More patients were vitamin D insufficient (n = 2257) than
      sufficient (n = 966). There were 240 patients with NMSC: 49 had an SCC, 163 had a
      BCC, and 28 had both. Vitamin D levels greater than 15 ng/mL ("not deficient
      level") were positively associated with NMSC (unadjusted odds ratio [OR], 1.7;
      95% confidence interval [CI], 1.04-2.7), and this association was sustained after
      additional risk factors were adjusted for (adjusted OR, 1.8; 95% CI, 1.1-2.9).
      The 25-OHD levels were similarly positively associated, though statistically
      insignificant, with NMSC occurring on less UV-exposed anatomical locations
      (adjusted OR, 2.2; 95% CI, 0.7-7.0), whether for SCC (adjusted OR, 3.2; 95% CI,
      0.4-24.0) or for BCC, although the risk estimate for BCC was lower (adjusted OR,
      1.7; 95% CI, 0.5-5.8). CONCLUSIONS: An increased baseline serum 25-OHD level was
      significantly associated with an increased NMSC risk. This association was
      positive, though nonsignificant on less UV-exposed body sites, and UV exposure
      remains a likely confounder. The complex and confounded relationship of vitamin
      D, UV, and NMSC makes classic epidemiological investigation difficult in the
      absence of carefully measured history of cumulative UV exposure.

PMID- 21844427
TI  - Guidelines for designing and reporting clinical trials in vitiligo.
AB  - OBJECTIVE: To create guidelines for randomized controlled trials (RCTs)
      investigating interventions used in the management of vitiligo. PARTICIPANTS:
      Guideline developers included authors (clinicians, patient representatives, and a
      statistician) of the Cochrane systematic review "Interventions for Vitiligo" plus
      the coordinator of the vitiligo priority-setting partnership at the Centre of
      Evidence-Based Dermatology at the University of Nottingham. EVIDENCE: The
      guidelines are based on the assessment of the quality of design and reporting of
      RCTs evaluating interventions for vitiligo included in the 2010 update of the
      Cochrane systematic review "Interventions for Vitiligo." CONSENSUS PROCESS: We
      reviewed and commented on the sources of bias in existing RCTs on interventions
      for vitiligo (selection bias, blinding assessment, attrition bias,
      characteristics of participants, interventions, and outcomes) based on the
      findings of the Cochrane review, and we used open discussion on guideline drafts
      focusing on the study question (participants, interventions, and outcomes), study
      design (research methods), and reporting. CONCLUSIONS: Much opportunity exists
      for improving the design and reporting of vitiligo clinical trials. The proposed
      guidelines will help overcome methodologic challenges faced when conducting RCTs
      to answer treatment questions.

PMID- 21844428
TI  - Propranolol vs corticosteroids for infantile hemangiomas: a multicenter
      retrospective analysis.
AB  - OBJECTIVE: To determine whether propranolol therapy is safe and effective and
      superior to oral corticosteroids for treating infantile hemangiomas (IHs).
      DESIGN: Multicenter retrospective chart review. SETTING: University of Miami and
      Miami Children's Hospital, Miami, Florida. Patients  The study included 110
      patients with IHs. MAIN OUTCOME MEASURES: The percentage of clearance was
      quantified by documented serial global photography and clinical examinations
      (length, height, and width) to segregate patients into 2 groups: patients who had
      clearance of 75% or more and patients who had less than 75% clearance. RESULTS:
      The mean duration of treatment was 7.9 months for propranolol and 5.2 months for
      oral corticosteroids. Fifty-six of 68 patients (82%) who were receiving
      propranolol achieved clearance of 75% or more compared with 12 of 42 patients
      (29%) who were receiving oral corticosteroids (P < .01). Adverse effects were
      minimal in the propranolol group: 1 patient had hypoglycemia and 2 patients had a
      nonspecifice skin eruption that was not associated with propranolol therapy. All
      42 patients in the corticosteroid group had 1 or more adverse effects (P < .01).
      Relapse after discontinuation of propranolol therapy occurred in 2 of the 68
      patients; however, both patients responded to propranolol therapy on reinitiation
      of treatment. Surgical referrals after treatment were required in 8 patients
      (12%) in the propranolol group and 12 patients (29%) in the oral corticosteroid
      group (P < .01). CONCLUSIONS: Propranolol therapy was more clinically effective
      and more cost-effective than oral corticosteroids in treating IHs. It also
      resulted in fewer surgical interventions and demonstrated better tolerance, with
      minimal adverse effects, compared with oral corticosteroids. Therefore,
      propranolol should be considered a first-line agent given its safety and efficacy
      in the treatment of IHs.

PMID- 21844429
TI  - Assessing dermatologists' ability to deliver a novel intervention to improve
      patients' use of sun protection: the ABC method of physician-patient
      communication.

PMID- 21844430
TI  - High clinical response rate of Sezary syndrome to immunomodulatory therapies:
      prognostic markers of response.
AB  - OBJECTIVES: To quantify response rates of Sezary syndrome (SS) to multimodality
      immunomodulatory therapy and to identify the important prognostic parameters that
      affect overall response to treatment. DESIGN: Retrospective cohort study.
      SETTING: Cutaneous T-cell lymphoma clinic at The Hospital at the University of
      Pennsylvania. PARTICIPANTS: Ninety-eight patients who met the revised
      International Society for Cutaneous Lymphomas (ISCL) and the European
      Organization of Research and Treatment of Cancer (EORTC) criteria for the
      diagnosis of SS and were seen over a 25-year period at the University of
      Pennsylvania. Intervention Patients were treated with at least 3 months of
      extracorporeal photopheresis and 1 or more systemic immunostimulatory agents.
      MAIN OUTCOME MEASURES: Overall response to treatment was the main measurement of
      outcome. RESULTS: A total of 73 patients had significant improvement with
      multimodality therapy: 30% had complete response, with clearing of all disease (n
      = 29), and 45% had partial response (n = 44). At baseline, the complete response
      group had a lower CD4/CD8 ratio than the nonresponse group (13.2 vs 44.2) (P =
      .04) and a lower median percentage of CD4(+)/CD26(-) cells (27.4% vs 57.2%) (P =
      .01) and CD4(+)/CD7(-) cells (20.0% vs 41.3%) (P < .01). Median monocyte
      percentage at baseline was higher for patients who had a complete response than
      for nonresponders (9.5% vs 7.3%) (P = .02). The partial response group did not
      have any statistically significant variables compared with the nonresponse group.
      CONCLUSIONS: In this large cohort study of patients with SS, a high clinical
      response rate was achieved using multiple immunomodulatory therapies. A lower
      CD4/CD8 ratio, a higher percentage of monocytes, and lower numbers of circulating
      abnormal T cells at baseline were the strongest predictive factors for complete
      response compared with nonresponse and warrant further examination in a larger
      cohort.

PMID- 21844431
TI  - Inferring causation from multiple regression: do not resuscitate?

PMID- 21844432
TI  - Surgery resident training in endoscopy: the saga continues.

PMID- 21844433
TI  - Resident self-other assessor agreement: influence of assessor, competency, and
      performance level.
AB  - OBJECTIVES: To review the literature on self-assessment in the context of
      resident performance and to determine the correlation between self-assessment
      across competencies in high- and low-performing residents and assessments
      performed by raters from a variety of professional roles (peers, nurses, and
      faculty). DESIGN: Retrospective analysis of prospectively collected anonymous
      self-assessment and multiprofessional (360) performance assessments by competency
      and overall. SETTING: University-based academic general surgical program.
      PARTICIPANTS: Sixty-two residents rotating in general surgery. MAIN OUTCOME
      MEASURES: Mean difference for each self-assessment dyad (self-peer, self-nurse,
      and self-attending physician) by resident performance quartile, adjusted for
      measurement error, correlation coefficients, and summed differences across all
      competencies. RESULTS: Irrespective of self-other dyad, residents asked to rate
      their global performance overestimated their skills. Residents in the upper
      quartile underestimated their specific skills while those in the lowest
      performing quartile overestimated their abilities when compared with faculty,
      peers, and especially nurse raters. Moreover, overestimation was greatest in
      competencies related to interpersonal skills, communication, teamwork, and
      professionalism. CONCLUSIONS: Rater, level of performance, and the competency
      being assessed all influence the comparison of the resident's self-assessment and
      those of other raters. Self-assessment of competencies related to behavior may be
      inaccurate when compared with raters from various professions. Residents in the
      lowest-performing quartile are least able to identify their weakness. These data
      have important implications for residents, program directors, and the public and
      suggest that strategies that help the lowest-performing residents recognize areas
      in need of improvement are needed.

PMID- 21844434
TI  - Our trainees' confidence: results from a national survey of 4136 US general
      surgery residents.
AB  - OBJECTIVES: To characterize factors shaping surgery resident confidence and
      determine whether confidence is associated with future specialty training.
      DESIGN: Cross-sectional study. SETTING: Survey administered at the 2008 American
      Board of Surgery In-Service Training Examination. PARTICIPANTS: All categorical
      general surgery residents. INTERVENTIONS: National Study of Expectations and
      Attitudes of Residents in Surgery survey. PARTICIPANTS: reported demographics and
      level of agreement for 46 items regarding confidence, training, and professional
      plans. MAIN OUTCOMES MEASURES: Survey items "My operating skill level is
      appropriate" and "I may not feel confident enough to perform procedures
      independently before training completion." We compared demographics and responses
      among residents who did/not feel confident. RESULTS: Response rate was 77.4%.
      Residents who were female, single, or without children and at a lower
      postgraduate year had less confidence in their operating skill, as did residents
      at larger, university-based programs, in the northeastern United States.
      Residents worried about competence were more likely to believe specialty training
      was needed (71.2% vs 60.2%; P < .001). After adjustment, residents dissatisfied
      with training were less likely to believe their skills were level appropriate
      (odds ratio, 0.13; P < .001) as were residents not comfortable asking for help
      (odds ratio, 0.48; P < .001). After adjustment, women were twice more likely than
      men to worry about competence after training; single residents were 1.36 times
      more likely than married residents to believe their skills were not level
      appropriate. Program location, type, and size remained associated with
      confidence, as did satisfaction and comfort asking for help. Residents worried
      about skills were more likely to plan for fellowship. CONCLUSIONS: Sex, marital
      status, children, and postgraduate year are predictors of confidence, as are
      program location, type, and size. Residency programs may target modifiable
      factors contributing to low surgical confidence.

PMID- 21844435
TI  - Pretraining and posttraining assessment of residents' performance in the fourth
      accreditation council for graduate medical education competency: patient
      communication skills.
AB  - HYPOTHESIS: Structured communication curricula will improve surgical residents'
      ability to communicate effectively with patients. DESIGN AND SETTING: A
      prospective study approved by the institutional review board involved 44
      University of Connecticut general surgery residents. Residents initially
      completed a written baseline survey to assess general communication skills
      awareness. In step 1 of the study, residents were randomized to 1 of 2
      simulations using standardized patient instructors to mimic patients receiving a
      diagnosis of either breast or rectal cancer. The standardized patient instructors
      scored residents' communication skills using a case-specific content checklist
      and Master Interview Rating Scale. In step 2 of the study, residents attended a 3
      part interactive program that comprised (1) principles of patient communication;
      (2) experiences of a surgeon (role as physician, patient, and patient's spouse);
      and (3) role-playing (3-resident groups played patient, physician, and observer
      roles and rated their own performance). In step 3, residents were retested as in
      step 1, using a crossover case design. Scores were analyzed using Wilcoxon signed
      rank test with a Bonferroni correction. RESULTS: Case-specific performance
      improved significantly, from a pretest content checklist median score of 8.5
      (65%) to a posttest median of 11.0 (84%) (P = .005 by Wilcoxon signed rank test
      for paired ordinal data)(n = 44). Median Master Interview Rating Scale scores
      changed from 58.0 before testing (P = .10) to 61.5 after testing (P = .94).
      Difference between overall rectal cancer scores and breast cancer scores also
      were not significant. CONCLUSIONS: Patient communication skills need to be taught
      as part of residency training. With limited training, case-specific skills
      (herein, involving patients with cancer) are likely to improve more than general
      communication skills.

PMID- 21844436
TI  - Liver transplantation for the treatment of liver metastases from neuroendocrine
      tumors: an analysis of the UNOS database.
AB  - OBJECTIVE: To determine outcomes in patients undergoing liver transplantation
      (LT) for metastatic neuroendocrine tumors (NETs). DESIGN: Retrospective analysis.
      SETTING: University of Kentucky Medical Center. PATIENTS: Patients undergoing LT
      performed for NET metastases from October 1, 1988, through January 31, 2008, were
      analyzed using the United Network for Organ Sharing database. Main Outcome
      Measure  Patient survival. RESULTS: During the study period, 87 280 LTs were
      performed. One hundred fifty LTs were performed for metastatic NETs. Among those
      150 patients undergoing LT, 51 patients (34.0%) had carcinoid, 6 had insulinoma
      (4.0%), 3 had glucagonoma (2.0%), 11 had gastrinoma (7.3%), and 9 had vasoactive
      intestinal peptide-secreting tumors (6.0%); an additional 70 (46.7%) had an
      unspecified NET. The mean (SE) age of the patients was 45.1 (12.5) years. The
      mean (SE) cold ischemic time was 8.9 (4.1) hours. One hundred forty-four patients
      were adults and 6 were children. Thirteen patients received another organ at the
      time of LT. During the same period, 4693 patients underwent transplantation for
      hepatocellular carcinoma. Overall, 1-, 3-, and 5-year survival rates for patients
      with NETs undergoing isolated LT were 81%, 65%, and 49%, respectively. No
      difference in survival was observed in patients with carcinoid vs noncarcinoid
      tumors (P = .84). No significant difference was observed in patient survival
      between those with metastatic NETs and those with hepatocellular carcinoma.
      Patients waiting for LT longer than 2 months had improved survival (P = .005).
      CONCLUSIONS: Patients with liver metastases from NETs who were undergoing LT had
      long-term survival similar to that of patients with hepatocellular carcinoma.
      Longer wait times were associated with better outcomes in our series. Waiting for
      disease to stabilize before considering patients with liver metastases from NETs
      for transplantation may be appropriate. Excellent results can be obtained in
      highly selected patients.

PMID- 21844437
TI  - Risk of comorbidities on postoperative outcomes in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: The effect of comorbidities on postoperative outcomes in patients
      with inflammatory bowel disease (IBD) has not been explored adequately. We
      evaluated the prevalence of comorbidities and their effect on postoperative
      outcomes after an IBD-related operation. METHODS: The Nationwide Inpatient Sample
      database was used to identify 35 588 patients with IBD who underwent an IBD
      related operation from January 1, 1995, through December 31, 2005. The presence
      of comorbid illness was assessed using the Elixhauser index. Multiple logistic
      regression analysis was performed to evaluate the effect of comorbidities on
      mortality rate after adjusting for age, sex, race, health insurance status, and
      admission type. Linear regression models were used to evaluate health care
      resource use. RESULTS: Postoperative mortality was 1.9%. As the number of
      comorbidities increased (ie, 0, 1, 2, or >=3), postoperative mortality increased
      (0.4%, 1.5%, 3.3%, and 7.9%, respectively). Congestive heart failure (odds ratio,
      3.50 [95% confidence interval, 2.63-4.62]), liver disease (3.15 [2.00-4.97]),
      thromboembolic disease (4.19 [3.37-5.21]), and renal disease (8.74 [5.44-14.05])
      were associated with a significant increase in mortality rate. Comorbidities
      associated with an increased risk of mortality also were associated with a
      significant increase in length of stay and hospital charges. CONCLUSIONS:
      Comorbidities were common in patients with IBD and they significantly increased
      the risk of postoperative mortality and health care use in patients with IBD.

PMID- 21844438
TI  - Effect of physician and hospital experience on patient outcomes for endovascular
      treatment of aortoiliac occlusive disease.
AB  - OBJECTIVE: To evaluate the effect of physician volume and specialty and hospital
      volume on population-level outcomes after endovascular repair of aortoiliac
      occlusive disease (AIOD). DESIGN: A retrospective cross-sectional analysis of all
      inpatients undergoing endovascular repair of AIOD. Physician volume was
      classified as low (<17 procedures per year [<50th percentile]) or high (>=17
      procedures per year). Physicians were defined as surgeons if they performed at
      least 1 carotid, aortic, or iliac endarterectomy; open aortic repair; above- or
      below-knee amputation; or aortoiliac-femoral bypass. Hospital volume was low
      (<116 procedures per year [<50th percentile]) or high (>=116 procedures per
      year). PATIENTS: Eight hundred eighteen inpatients who underwent endovascular
      repair of AIOD in the Healthcare Cost and Utilization Project Nationwide
      Inpatient Sample from January 2003 through December 2007. SETTING: National
      hospital database. MAIN OUTCOME MEASURES: In-hospital complications and
      mortality, length of stay, and cost. RESULTS: Of the 818 procedures, 59.0% of
      high-volume physicians were surgeons and 65.0% practiced at high-volume
      hospitals. Unadjusted complication rates were significantly higher for low-volume
      compared with high-volume physicians (18.7% vs 12.6%; P = .02); rates were not
      significantly different by physician specialty (P = .88) or hospital volume (P =
      .16). Shorter length of stay was associated with high-volume physicians (P =
      .001), high-volume hospitals (P = .001), and surgeon providers (P = .03), whereas
      decreased cost was associated with physician specialty (P = .004). On
      multivariate analysis, high physician volume was associated with significantly
      lower complications (P = .04); high hospital volume, with shorter length of stay
      (P = .002); and nonsurgeons, with higher costs (P = .05). CONCLUSIONS: Overall,
      volume at the physician and hospital levels appears to be a robust predictor of
      patient outcomes after endovascular interventions for AIOD. Surgeons performing
      endovascular procedures for AIOD have a decreased associated hospital cost
      compared with nonsurgeons.

PMID- 21844439
TI  - Legislating change in surgical residency.
AB  - The Patient Protection and Affordable Care Act, also known as the House of
      Representatives Bill HR 3590, was created to improve the quality of patient care
      and access to health care for American citizens. Provisions of this bill are
      likely to have both intended and unintended consequences on surgical education.
      The purpose of this article is to explore the ways in which HR 3590 may affect
      the educational experience of surgical house officers at teaching hospitals.

PMID- 21844440
TI  - Harvey Cushing's operative treatment of metastatic breast cancer to the central
      nervous system in the early 1900s.
AB  - BACKGROUND: A review of the surgical cases of Harvey Cushing, MD, at The Johns
      Hopkins Hospital provided insight into his early work treating breast cancer
      metastasis to the central nervous system (CNS). At the time, neurologic surgery
      was in its infancy. Metastases of breast carcinoma to the CNS were recognized;
      however, many surgeons of the era adhered to a general principle of not operating
      in these situations. METHODS: The Johns Hopkins Hospital surgical records from
      1896 to 1912 were reviewed. Four cases in which Cushing treated patients with a
      history of breast cancer who were diagnosed as having CNS metastasis were
      selected for further study. RESULTS: Cushing performed surgery on 4 patients with
      suspected CNS metastasis in the early 1900s. For a spinal metastasis, Cushing
      performed a laminectomy and intradural exploratory surgery. His treatments in
      cerebral cases sought to relieve increased intracranial pressure through
      decompression. He resected the lesions when they could be located. CONCLUSIONS:
      From the start of his career as a neurosurgeon, Cushing chose to perform surgery
      on patients with suspected CNS metastasis in an attempt to palliate some of their
      symptoms. Although his patients did not survive long after the procedures, they
      did experience temporary relief of symptoms that likely encouraged Cushing's
      continued operations in such situations and laid the foundation for future
      therapies for these patients.

PMID- 21844441
TI  - Less may be better: axillary dissection is unnecessary in some patients with a
      positive sentinel lymph node.

PMID- 21844442
TI  - Enzyme elevation after coronary bypass surgery: cause or effect?

PMID- 21844443
TI  - Image of the month--quiz case. Paraganglioma.

PMID- 21844444
TI  - Image of the month--quiz case. Typhoid intestinal perforation.

PMID- 21844445
TI  - Image of the month--quiz case. Isolated common hepatic duct injury with anomalous
      right hepatic duct anatomy.

PMID- 21844446
TI  - The "vulnerable stage" of general surgery residency.

PMID- 21844447
TI  - Fixing the mesh in inguinal hernia repair: where do we stand?

PMID- 21844448
TI  - Successful treatment of subacute lupus erythematosus with ustekinumab.

PMID- 21844449
TI  - Prevent rather than treat postherpetic neuralgia by prescribing gabapentin
      earlier in patients with herpes zoster: comment on "incidence of postherpetic
      neuralgia after combination treatment with gabapentin and valacyclovir in
      patients with acute herpes zoster".

PMID- 21844450
TI  - Dermatologists do not yet fully understand the clinical significance of
      antibiotic use and bacterial resistance in patients with acne: comment on
      "Antibiotics, acne, and Staphylococcus aureus colonization.

PMID- 21844452
TI  - Dermoscopic features of skin lesions in patients with mastocytosis.
AB  - OBJECTIVES: To evaluate dermoscopic features in a group of 127 patients with
      mastocytosis in the skin and to investigate the relationship between different
      dermoscopic patterns and other clinical and biological characteristics of the
      disease. DESIGN: Clinical and laboratory data were compared among patients with
      mastocytosis grouped according to the different dermoscopic patterns. SETTING:
      Patients were selected from the Instituto de Estudios de Mastocitosis de Castilla
      La Mancha and the Department of Dermatology of Hospital Universitario Ramon y
      Cajal from April 1 through September 30, 2009. Patients Overall, 127 consecutive
      patients (70 females [55.1%] and 57 males [44.9%]; median age, 17 years; range, 0
      81 years) with mastocytosis in the skin were included in the study. MAIN OUTCOME
      MEASURES: Evaluation of dermoscopic patterns and investigation of potential
      predictive factors for more symptomatic forms of the disease according to the
      need for daily antimediator therapy. RESULTS: Four distinct dermoscopic patterns
      were observed: yellow-orange blot, pigment network, reticular vascular pattern,
      and (most frequently) light-brown blot. A reticular vascular pattern was
      identified in all telangiectasia macular eruptiva and some maculopapular
      mastocytosis. In turn, all patients with mastocytoma displayed the yellow-orange
      blot pattern. The reticular vascular dermoscopic pattern was associated with the
      need for daily antimediator therapy; this pattern, together with serum tryptase
      levels and plaque-type mastocytosis, represented the best combination of
      independent factors to predict the need for maintained antimediator therapy.
      CONCLUSIONS: Dermoscopy is a feasible method for the subclassification of
      mastocytosis. Of note, a reticular vascular pattern is more frequently associated
      with the need for antimediator therapy.

PMID- 21844454
TI  - Usefulness of Interferon-gamma release assays in the diagnosis of erythema
      induratum.
AB  - BACKGROUND: Erythema induratum (EI) manifests as tender indurated nodules on the
      lower legs. It may be associated with concomitant active tuberculosis (TB) and is
      considered a hypersensitivity reaction to mycobacterial antigens. However, the
      results of Mycobacterium cultures are rarely positive, and the tuberculin skin
      test is of limited usefulness in populations exposed to bacille Calmette-Guerin
      (BCG). Interferon-gamma release assays (IGRAs) are alternatives to the tuberculin
      skin test and have high specificity. We explored the use of IGRAs as an adjunct
      in the diagnosis of EI. We describe 5 patients with positive tuberculin skin test
      results and a history of vaccination against BCG or TB in whom IGRAs supported
      the diagnosis of EI. OBSERVATIONS: All patients were initially seen with tender
      nodules on the lower legs and a history of BCG vaccination or TB. Tuberculin skin
      test results were positive, and chest radiographic results were normal. The
      results of Mycobacterium cultures were negative in all patients, and biopsy
      specimens were compatible with EI. Interferon-gamma release assays were performed
      in all patients and supported initiation of anti-TB treatment in 4 of 5 patients.
      Conclusion  Interferon-gamma release assays may have value as an adjunct in the
      diagnosis of EI, particularly in the setting of prior BCG exposure.

PMID- 21844453
TI  - Clonal T-cell receptor beta-chain gene rearrangements in differential diagnosis
      of lymphomatoid papulosis from skin metastasis of nodal anaplastic large-cell
      lymphoma.
AB  - BACKGROUND: In patients with a history of nodal anaplastic large-cell lymphoma
      (ALCL), differentiation of type C lymphomatoid papulosis from cutaneous
      involvement of systemic ALCL may be challenging because the 2 entities may
      exhibit identical histologic features. Although metastatic ALCL generally carries
      the same clone as the primary lymphoma, expression of a distinct clone likely
      represents a distinct process. OBSERVATIONS: A 54-year-old white man had a
      history of anaplastic lymphoma kinase 1-negative ALCL in the right inguinal lymph
      node 6 years ago. A complete response was achieved after 6 cycles of CHOP
      (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone
      administered in 21-day cycles) and radiation therapy. After 31/2 years, the
      patient observed waxing and waning papules and nodules. Examination of the biopsy
      specimen revealed a dense CD30(+) lymphocytic infiltrate; no evidence of systemic
      malignancy was evident on positron emission tomography. Although clinically the
      presentation was consistent with lymphomatoid papulosis, metastatic ALCL had to
      be excluded. Polymerase chain reaction analysis with T-cell receptor gamma-chain
      gene rearrangement (TCR-gammaR) was performed on the original lymph node and new
      skin lesions. Results of the TCR-gammaR analysis were positive for clonality in
      both lesions. However, separate clonal processes were identified. The
      identification of distinct clones supported the clinical impression of
      lymphomatoid papulosis. CONCLUSION: Polymerase chain reaction analysis of TCR
      gammaR is a useful method for distinguishing different clonal processes and is
      recommended when differentiation of primary and secondary lymphoproliferative
      disorders is required.

PMID- 21844455
TI  - Epidermolysis bullosa pruriginosa masquerading as psychogenic pruritus.
AB  - BACKGROUND: Epidermolysis bullosa pruriginosa is a rare clinical subtype of
      dystrophic epidermolysis bullosa characterized by intense pruritus, secondary
      scratching-induced lesions, and pronounced scarring. OBSERVATIONS: We describe a
      patient with epidermolysis bullosa pruriginosa who was misdiagnosed as having
      psychogenic pruritus for several years. Except for nail (toenail) dystrophy, no
      features of the disease were evident among his immediate family members. An
      underlying new heterozygous donor splice-site mutation in the type VII collagen
      gene (IVS55 + 1G>C) was found in both the patient and his family members with
      nail dystrophy. Inheritance was autosomal dominant. The patient was treated with
      cyclosporine and experienced significant reduction in pruritus, with subsequent
      improvement of the skin condition. CONCLUSIONS: Pruritus is an important factor
      in the development of epidermolysis bullosa pruriginosa and is the focus of
      management. Patients with this inherited skin disorder can be easily misdiagnosed
      as having psychogenic pruritus, and this article aims to make physicians aware of
      this diagnostic pitfall.

PMID- 21844457
TI  - Atopic dermatitis and attention-deficit/hyperactivity disorder: is there an
      association?

PMID- 21844458
TI  - Prevalence and etiology of central centrifugal cicatricial alopecia.

PMID- 21844459
TI  - Tender papule on the finger of a child--quiz case.

PMID- 21844460
TI  - Papular eruption in a patient with leukemia--quiz case.

PMID- 21844461
TI  - A bonelike protrusion on the toe--quiz case.

PMID- 21844462
TI  - Skin-colored nodules on the knuckles--quiz case.

PMID- 21844463
TI  - New contrast stain for the rapid diagnosis of onychomycosis.

PMID- 21844464
TI  - Tanning and sun-protection portrayal in magazine images.

PMID- 21844465
TI  - Use of electronic medical records to ascertain depth of SEER-reported melanomas
      of unknown tumor thickness.

PMID- 21844466
TI  - The presence of IgM antiphospholipid antibodies in patients with Henoch-Schonlein
      purpura and recurrent palpable purpura.

PMID- 21844467
TI  - Gluten-free diet in patients with dermatitis herpetiformis: not only a matter of
      skin.

PMID- 21844468
TI  - Psoriasis, addiction, and personality.

PMID- 21844469
TI  - Isolated sarcoidal granulomas on the tongue.

PMID- 21844470
TI  - Melanoma occurring during treatment with fingolimod for multiple sclerosis: a
      case report.

PMID- 21844471
TI  - Lymphomatoid drug reaction to ustekinumab.

PMID- 21844472
TI  - Keratitis-ichthyosis-deafness syndrome: response to alitretinoin and review of
      literature.

PMID- 21844473
TI  - S-100-Negative, CD1a-positive histiocytosis: a new variant with features of both
      indeterminate cells and interstitial dermal dendrocytes.

PMID- 21844474
TI  - Resolution of granular parakeratosis with topical calcitriol.

PMID- 21844475
TI  - Complete response of metastatic malignant hidradenocarcinoma to capecitabine
      treatment.

PMID- 21844476
TI  - Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation
      of keratin 1.

PMID- 21844477
TI  - Occurrence of penile intraepithelial neoplasia following adalimumab treatment for
      psoriatic arthritis.

PMID- 21844478
TI  - Reflectance confocal microscopic features of dermatophytes, scabies, and demodex.

PMID- 21844479
TI  - Auricular keloids: combined therapy with a new pressure device.
AB  - OBJECTIVE: To develop a new, custom-made pressure device that can be used with
      established designs as an adjuvant therapy for optimized treatment of auricular
      keloids. METHODS: Seven patients (4 males, 3 females; mean [SD] age, 22.6 [8.3]
      years) were treated with surgical excision and corticosteroid injection followed
      by application of our new auricular pressure device. RESULTS: All patients
      tolerated the adjuvant therapy and wore the device overnight for 5 nights per
      week. Usage was not interrupted or cancelled. No recurrence was observed during
      the follow-up period (mean [SD] duration of follow-up, 24 [6] months). All
      patients were satisfied with the results; none described pruritus, pain, or
      dysesthesia. CONCLUSION: Overnight usage of the new pressure device seems to be a
      safe and effective extension of established auricular keloid therapy with the
      potential for prophylaxis of recurrence.

PMID- 21844480
TI  - Comparison of effectiveness of silicone gel sheeting with microporous paper tape
      in the prevention of hypertrophic scarring in a rabbit model.
AB  - OBJECTIVE: To determine the effectiveness of treating scars with microporous
      paper tape or silicone gel sheeting (SGS) in preventing hypertrophic scarring.
      METHODS: Forty hypertrophic scars were induced in a validated rabbit ear model.
      Wounds were randomized and bandaged for 30 days with either SGS (20 wounds),
      paper tape (20 wounds), or untreated controls (40 wounds). Two outcome measures
      of hypertrophic scarring included (1) histologic measurement of scar elevation
      index (SEI) and (2) blinded photograph analysis using a visual analog scale.
      RESULTS: In histologic comparison, no difference in mean (SE) SEI between
      treatment groups was seen (paper tape group, 1.32 [0.2]; SGS group, 1.41 [0.18];
      control, 1.35 [0.23]; P = .51). In photographic analysis, both treatment groups
      were superior to the control group (P < .01), whereas no difference was seen
      between the SGS and paper tape groups (P = .88). CONCLUSIONS: Paper tape and SGS
      demonstrated equal effectiveness in the prevention of hypertrophic scarring on
      visual analysis, whereas histologic analysis demonstrated no difference in
      treatment groups from controls. The effectiveness of paper tape in preventing
      hypertrophic scarring in humans will require further laboratory and clinical
      investigation.

PMID- 21844481
TI  - Laser facial nerve welding in a rabbit model.
AB  - OBJECTIVE: To assess the feasibility of laser tissue welding for repair of facial
      nerve injury. METHODS: In a prospective in vivo animal survival surgery model,
      rabbit facial nerve injury was followed by either standard suture neurorrhaphy or
      laser tissue welding using a diode laser (808 +/- 1 nm) to weld biological
      solder. Rabbits were evaluated at 4, 8, 12, and 16 weeks by facial videography
      and electromyography. Histopathological analysis of the repair was performed at 4
      and 16 weeks. RESULTS: Videographic analysis demonstrated the laser tissue
      welding repair trended toward superior outcomes compared with suture neurorrhaphy
      at all 4 time points. Electrophysiological analysis demonstrated similar or
      better results, with statistically significant improvement at week 16 (P < .05).
      Histologic analysis demonstrated no difference in axon organization or
      extravasation between groups; however, the laser nerve repair created a greater
      initial inflammatory reaction. An analysis of operative time demonstrated
      significantly decreased time and ease of use for laser tissue welding.
      CONCLUSIONS: This pilot study demonstrates that laser nerve welding may be an
      expedient, feasible, and safe method for facial nerve repair in a rabbit model.
      Further experiments with larger numbers are needed to provide additional evidence
      that laser tissue welding produces a neurorrhaphy that has functional,
      electrophysiological, and histological results that could rival traditional
      suture neurorrhaphy.

PMID- 21844482
TI  - Effects of renal sympathetic denervation on blood pressure, sleep apnea course,
      and glycemic control in patients with resistant hypertension and sleep apnea.
AB  - Percutaneous renal sympathetic denervation by radiofrequency energy has been
      reported to reduce blood pressure (BP) by the reduction of renal sympathetic
      efferent and afferent signaling. We evaluated the effects of this procedure on BP
      and sleep apnea severity in patients with resistant hypertension and sleep apnea.
      We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3
      women; median age: 49.5 years) who underwent renal denervation and completed 3
      month and 6-month follow-up evaluations, including polysomnography and selected
      blood chemistries, and BP measurements. Antihypertensive regimens were not
      changed during the 6 months of follow-up. Three and 6 months after the
      denervation, decreases in office systolic and diastolic BPs were observed
      (median: -34/-13 mm Hg for systolic and diastolic BPs at 6 months; both P<0.01).
      Significant decreases were also observed in plasma glucose concentration 2 hours
      after glucose administration (median: 7.0 versus 6.4 mmol/L; P=0.05) and in
      hemoglobin A1C level (median: 6.1% versus 5.6%; P<0.05) at 6 months, as well as a
      decrease in apnea-hypopnea index at 6 months after renal denervation (median:
      16.3 versus 4.5 events per hour; P=0.059). In conclusion, catheter-based renal
      sympathetic denervation lowered BP in patients with refractory hypertension and
      obstructive sleep apnea, which was accompanied by improvement of sleep apnea
      severity. Interestingly, there are also accompanying improvements in glucose
      tolerance. Renal sympathetic denervation may conceivably be a potentially useful
      option for patients with comorbid refractory hypertension, glucose intolerance,
      and obstructive sleep apnea, although further studies are needed to confirm these
      proof-of-concept data.

PMID- 21844483
TI  - Guidelines, inertia, and judgment.

PMID- 21844484
TI  - Estrogen receptor GPR30 reduces oxidative stress and proteinuria in the salt
      sensitive female mRen2.Lewis rat.
AB  - The current study assessed whether activation of the novel estrogen receptor
      GPR30 ameliorates salt-dependent renal damage in intact mRen2.Lewis (mRen2)
      females. Hemizygous mRen2 rats were maintained on either a normal salt (0.5% Na)
      or high-salt (HS; 4.0% Na) diet for 10 weeks (5 to 15 weeks of age), and HS
      animals were treated with the GPR30 agonist G-1 or vehicle for 2 weeks. Systolic
      blood pressure markedly increased with HS diet (149+/-3 to 219+/-5 mm Hg;
      P<0.01), but G-1 did not influence pressure (P=0.42). G-1 and estradiol induced
      relaxation of preconstricted mesenteric vessels from normal salt mRen2 rats, but
      both responses were attenuated in the HS group. Despite the lack of an effect on
      blood pressure, G-1 decreased renal hypertrophy, proteinuria, urinary 8
      isoprostane excretion, and tubular 4-hydroxynonenal staining. HS diet
      significantly increased GPR30 mRNA (1.01+/-0.04 versus 1.59+/-0.13; P<0.01) and
      protein (0.60+/-0.31 versus 3.99+/-0.75; P<0.01) in the renal cortex. GPR30 was
      highly expressed in the brush border of proximal tubules and colocalized with
      megalin. Finally, megalin expression was reduced by HS diet and restored with G
      1. We conclude that GPR30-mediated beneficial effects in salt-sensitive mRen2
      females occurred independent of changes in systolic blood pressure. The failure
      of G-1 to influence pressure may reflect a salt-induced impairment in GPR30
      mediated vasorelaxation. The renoprotective actions of GPR30 may involve
      attenuation of tubular oxidative stress and activation of megalin-mediated
      protein reabsorption.

PMID- 21844485
TI  - Angiotensin II upregulates protein phosphatase 2Calpha and inhibits AMP-activated
      protein kinase signaling and energy balance leading to skeletal muscle wasting.
AB  - Congestive heart failure and chronic kidney disease are characterized by
      chronically elevated angiotensin II (Ang II) and muscle wasting. Ang II causes
      skeletal muscle wasting by reducing appetite and by enhancing catabolism. The
      serine/threonine kinase AMP-activated protein kinase (AMPK) functions mainly as a
      sensor of cellular energy status. It is energy sparing and favors ATP generation.
      We hypothesized that Ang II induces muscle wasting in part by inhibiting AMPK
      signaling and altering cellular energy balance. Our results show that Ang II
      infusion in mice reduced gastrocnemius muscle weight by 26% and depleted ATP by
      74%. In addition, Ang II upregulated protein phosphatase 2Calpha by 2.6-fold and
      reduced AMPK phosphorylation and signaling in muscle. Importantly, the
      pharmacological AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside
      restored AMPK activity to levels of pair-fed controls and reversed Ang II
      mediated ATP depletion and muscle wasting. Moreover, 5-aminoimidazole-4
      carboxamide ribonucleoside activated Akt and inhibited Ang II-induced increases
      in E3 ubiquitin ligase expression. These novel results demonstrate critical roles
      for energy depletion and AMPK inhibition in Ang II-induced skeletal muscle
      wasting and suggest a therapeutic potential for AMPK activators in diseases
      characterized by muscle wasting.

PMID- 21844486
TI  - Renal sympathetic denervation: a novel intervention for resistant hypertension,
      insulin resistance, and sleep apnea.

PMID- 21844487
TI  - Central angiotensin (1-7) enhances baroreflex gain in conscious rabbits with
      heart failure.
AB  - In chronic heart failure (CHF), arterial baroreflex function is impaired, in
      part, by activation of the central renin-angiotensin system. A metabolite of
      angiotensin (Ang) II, Ang-(1-7), has been shown to exhibit cardiovascular effects
      that are in opposition to that of Ang II. However, the action of Ang-(1-7) on
      sympathetic outflow and baroreflex function is not well understood, especially in
      CHF. The aim of this study was to determine the effect of intracerebroventricular
      infusion of Ang-(1-7) on baroreflex control of heart rate and renal sympathetic
      nerve activity in conscious rabbits with CHF. We hypothesized that central Ang-(1
      7) would improve baroreflex function in CHF. Ang-(1-7) (2 nmol/1 MUL per hour) or
      artificial cerebrospinal fluid (1 MUL per hour) was infused by an osmotic
      minipump for 4 days in sham and pacing-induced CHF rabbits (n=3 to 6 per group).
      Ang-(1-7) treatment had no effects in sham rabbits but reduced heart rate and
      increased baroreflex gain (7.4+/-1.5 versus 2.5+/-0.4 bpm/mm Hg; P<0.05) in CHF
      rabbits. The Ang-(1-7) antagonist A779 (8 nmol/1 MUL per hour) blocked the
      improvement in baroreflex gain in CHF. Baroreflex gain increased in CHF+Ang-(1-7)
      animals when only the vagus was allowed to modulate baroreflex control by acute
      treatment with the beta-1 antagonist metoprolol, indicating increased vagal tone.
      Baseline renal sympathetic nerve activity was significantly lower, and baroreflex
      control of renal sympathetic nerve activity was enhanced in CHF rabbits receiving
      Ang-(1-7). These data suggest that augmentation of central Ang-(1-7) inhibits
      sympathetic outflow and increases vagal outflow in CHF, thus contributing to
      enhanced baroreflex gain in this disease state.

PMID- 21844488
TI  - Receptor for activated protein kinase C1 regulates cell proliferation by
      modulating calcium signaling.
AB  - Receptor for activated protein kinase C1 (RACK1) is an intracellular scaffolding
      protein known to interact with the inositol-1,4,5-trisphosphate receptor and
      thereby enhance calcium release from the sarcoplasmic reticulum. Because calcium
      signaling may affect vascular smooth muscle cell proliferation, we investigated
      whether RACK1 regulates proliferation of rat preglomerular microvascular smooth
      muscle cells. Western blot analysis indicated that preglomerular microvascular
      smooth muscle cells robustly express RACK1 protein, and coimmunoprecipitation
      experiments demonstrated that RACK1 binds the inositol-1,4,5-trisphosphate
      receptor. RACK1 small interfering RNA (siRNA) decreased RACK1 mRNA and protein
      expression, significantly (P=0.0225) reduced steady-state basal levels of
      intracellular calcium (6712+/-156 versus 7408+/-248, arbitrary fluorescence units
      in RACK1 siRNA-treated versus control cells, respectively) and significantly
      (P<0.0001) decreased cell proliferation by ~50%. Xestospongin C and 2
      aminoethoxydiphenyl borate (antagonists of inositol-1,4,5-trisphosphate
      receptors), cyclopiazonic acid (sarcoplasmic reticulum Ca(2+)-ATPase inhibitor),
      and calmidazolium (calmodulin inhibitor) mimicked the effects of RACK1 siRNA on
      proliferation, and RACK1 siRNA had no additional effects on proliferation in the
      presence of these agents. RACK1 siRNA did not affect the expression of cyclin
      D1/2 or phosphorylation of retinoblastoma protein (progrowth cell cycle
      regulators), yet it caused compensatory decreases in the expression of
      p21(Cip1/Waf1) and p27(Kip1) (antigrowth cell cycle regulators). Like
      preglomerular microvascular smooth muscle cells, glomerular mesangial cells also
      expressed high levels of RACK1, and RACK1 siRNA inhibited their proliferation. In
      conclusion, RACK1 modulates proliferation of preglomerular microvascular smooth
      muscle cells and glomerular mesangial cells, likely via the inositol-1,4,5
      trisphosphate receptor/calcium/calmodulin pathway. RACK1 may represent a novel
      druggable target for treating renal diseases, such as glomerulosclerosis.

PMID- 21844489
TI  - Preeclampsia is associated with persistent postpartum cardiovascular impairment.
AB  - Preeclampsia is associated with asymptomatic global left ventricular abnormal
      function and geometry during the acute phase of the disorder. These subclinical
      abnormalities in cardiac findings are known to be important in cardiovascular
      risk stratification for nonpregnant patients. Furthermore, epidemiological
      studies have also demonstrated a relationship between preeclampsia and cardiac
      morbidity and mortality later in life. The aim of this study was to evaluate the
      postpartum natural history and clinical significance of asymptomatic left
      ventricular impairment known to occur with acute preeclampsia. This was a
      prospective longitudinal case-control study of 64 subjects with preeclampsia and
      78 matched controls. There were 3 time point assessments, pregnancy and 1 and 2
      years postpartum. The assessments included a medical and family history, blood
      pressure profile, echocardiography, and 12-lead ECG. At 1 year postpartum,
      asymptomatic left ventricular moderate-severe dysfunction/hypertrophy was
      significantly higher in preterm preeclampsia (56%) compared with term
      preeclampsia (14%) or matched controls (8%; P values <0.001). The risk of
      developing essential hypertension within 2 years was significantly higher in both
      preterm preeclamptic women and those with persistent left ventricular moderate
      severe abnormal function/geometry. The cardiovascular implications of
      preeclampsia do not end with the birth of the infant and placenta. The majority
      of preterm preeclamptic women have stage B asymptomatic heart failure postpartum,
      and 40% develop essential hypertension within 1 to 2 years after pregnancy. Women
      with a history of preterm preeclampsia may benefit from formal cardiovascular
      risk assessment in the 1 to 2 years after delivery to identify those who would
      benefit from targeted therapeutic intervention.

PMID- 21844490
TI  - Treatment intensification in a hypertension telemanagement trial: clinical
      inertia or good clinical judgment?
AB  - Clinical inertia represents a barrier to hypertension management. As part of a
      hypertension telemanagement trial designed to overcome clinical inertia, we
      evaluated study physician reactions to elevated home blood pressures. We studied
      296 patients from the Hypertension Intervention Nurse Telemedicine Study who
      received telemonitoring and study physician medication management. When a
      patient's 2-week mean home blood pressure was elevated, an "intervention alert"
      prompted study physicians to consider treatment intensification. We examined
      treatment intensification rates and subsequent blood pressure control. Patients
      generated 1216 intervention alerts during the 18-month intervention. Of 922
      eligible intervention alerts, study physicians intensified treatment in 374
      (40.6%). Study physician perception that home blood pressure was acceptable was
      the most common rationale for nonintensification (53.7%). When "blood pressure
      acceptable" was the reason for not intensifying treatment, the mean blood
      pressure was lower than for intervention alerts where treatment intensification
      occurred (135.3/76.7 versus 143.2/80.6 mm Hg; P<0.0001). Blood pressure
      acceptable intervention alerts were associated with the lowest incidence of
      repeat alerts (hazard ratio: 0.69 [95% CI: 0.58 to 0.83]), meaning that the
      patient home blood pressure was less likely to subsequently rise above goal,
      despite apparent clinical inertia. This telemedicine intervention targeting
      clinical inertia did not guarantee treatment intensification in response to
      elevated home blood pressures. However, when physicians did not intensify
      treatment, it was because blood pressure was closer to an acceptable threshold,
      and repeat blood pressure elevations occurred less frequently. Failure to
      intensify treatment when home blood pressure is elevated may, at times, represent
      good clinical judgment, not clinical inertia.

PMID- 21844491
TI  - Is pressure decrease at peak hyperemia attributed to Poiseuille or Bernoulli or
      both?

PMID- 21844492
TI  - Initial experience with transradial access for carotid artery stenting.
AB  - We report our experience using transradial access (TRA) for carotid artery
      stenting (CAS). Eighty-eight patients underwent CAS using a nonfemoral approach,
      79 of them by TRA. Carotid artery stenting was performed using standard
      techniques with a long hydrophilic sheath. Mean age was 69.5 years. A total of 46
      patients were symptomatic and 34 were asymptomatic. Transradial access and
      procedural success were achieved in 98.8% and 96.6% of the cases, respectively.
      There were no deaths, myocardial infarction, or radial access site complications.
      In all, 2 patients sustained a stroke, 1 hemorrhage, and 1 ischemia. Carotid
      artery stenting using TRA was safe and technically feasible.

PMID- 21844493
TI  - Degenerative (true) superficial temporal artery aneurysm: a case report with
      review of literature.
AB  - This is a case report of a 72-year-old female who presented to our clinic with
      right temple mass that was found incidentally on a magnetic resonance imaging
      (MRI) of her head about 2 years ago, as part of a stroke workup. However, it was
      thought to be a sebaceous cyst and left as such. The patient then experienced a
      rapid increase in the size of the mass about 2 weeks prior to her presentation to
      us. On examination, she had a 2 * 2 cm pulsating aneurysmal mass over the right
      temporal fossa, which was felt to be an aneurysm of the superficial temporal
      artery and was confirmed by a color duplex ultrasound examination. Open surgical
      resection with primary ligation of both proximal and distal branches was achieved
      under local anesthesia. Pathology confirmed a true (degenerative) aneurysm of the
      superficial temporal artery. Her postoperative course was uneventful. This case
      report describes this rare entity along with a review of the literature.

PMID- 21844494
TI  - Outcome analyses after the first admission to an intensive care unit in patients
      with advanced cancer referred to a phase I clinical trials program.
AB  - PURPOSE: This study assessed outcomes of individuals with advanced cancer who
      required admission to an intensive care unit (ICU) after referral for an early
      clinical trial because they did not respond to conventional therapy. PATIENTS AND
      METHODS: Outcome analyses were conducted for 212 consecutive patients admitted to
      The University of Texas MD Anderson Cancer Center ICU after being seen in the
      phase I clinic starting on May 1, 2007. All data were obtained by a review of
      electronic medical records of patients. RESULTS: The median survival of 212
      patients with advanced cancer referred to phase I care after the initial ICU
      admission was 3.2 weeks (95% CI, 2.5 to 4.9 weeks). Patients who underwent
      cardiopulmonary resuscitation (CPR) succumbed within a median survival of 1 day
      (75% and 25% estimated survival of 1 and 3 days, respectively). Patients admitted
      for a postsurgical intervention did better than patients admitted for a
      nonsurgical intervention (median survival, 21.5 versus 2.1 weeks; P < .0001). The
      multivariate analysis revealed that a nonsurgical intervention, hypoalbuminemia,
      and higher Acute Physiology and Chronic Health Evaluation II scores were
      associated with poor overall survival. CONCLUSION: The outcome of patients in a
      phase I clinic after initial ICU admission was poor, particularly when admission
      was for a nonsurgical intervention and/or when CPR was needed.

PMID- 21844495
TI  - Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal
      doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2
      randomized phase III trial.
AB  - PURPOSE: Carboplatin/paclitaxel is the standard first-line chemotherapy for
      patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian
      Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether
      carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than
      standard chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with
      stage IC to IV ovarian cancer (age <= 75 years; Eastern Cooperative Oncology
      Group performance status <= 2) were randomly assigned to carboplatin area under
      the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30
      mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free
      survival (PFS). With 632 events in 820 enrolled patients, the study would have
      80% power to detect a 0.80 hazard ratio (HR) of PFS. RESULTS: Eight hundred
      twenty patients were randomly assigned. Disease stages III and IV were prevalent.
      Occurrence of PFS events substantially slowed before obtaining the planned
      number. Therefore, in concert with the Independent Data Monitoring Committee,
      final analysis was performed with 556 events, after a median follow-up of 40
      months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and
      carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58).
      Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and
      carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32).
      Carboplatin/PLD produced a similar response rate but different toxicity (less
      neurotoxicity and alopecia but more hematologic adverse effects). There was no
      relevant difference in global quality of life after three and six cycles.
      CONCLUSION: Carboplatin/PLD was not superior to carboplatin/paclitaxel, which
      remains the standard first-line chemotherapy for advanced ovarian cancer.
      However, given the observed CIs and the different toxicity, carboplatin/PLD could
      be considered an alternative to standard therapy.

PMID- 21844496
TI  - Salivary duct carcinoma: targeting the phosphatidylinositol 3-kinase pathway by
      blocking mammalian target of rapamycin with temsirolimus.

PMID- 21844497
TI  - Bendamustine combined with rituximab in patients with relapsed and/or refractory
      chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic
      Lymphocytic Leukemia Study Group.
AB  - PURPOSE: The objective of this trial was to evaluate safety and efficacy of
      bendamustine combined with rituximab (BR) in patients with relapsed and/or
      refractory chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Seventy
      eight patients, including 22 patients with fludarabine-refractory disease (28.2%)
      and 14 patients (17.9%) with deletion of 17p, received BR chemoimmunotherapy.
      Bendamustine was administered at a dose of 70 mg/m(2) on days 1 and 2 combined
      with rituximab 375 mg/m(2) on day 0 of the first course and 500 mg/m(2) on day 1
      during subsequent courses for up to six courses. RESULTS: On the basis of intent
      to-treat analysis, the overall response rate was 59.0% (95% CI, 47.3% to 70.0%).
      Complete response, partial response, and nodular partial response were achieved
      in 9.0%, 47.4%, and 2.6% of patients, respectively. Overall response rate was
      45.5% in fludarabine-refractory patients and 60.5% in fludarabine-sensitive
      patients. Among genetic subgroups, 92.3% of patients with del(11q), 100% with
      trisomy 12, 7.1% with del(17p), and 58.7% with unmutated IGHV status responded to
      treatment. After a median follow-up time of 24 months, the median event-free
      survival was 14.7 months. Severe infections occurred in 12.8% of patients. Grade
      3 or 4 neutropenia, thrombocytopenia, and anemia were documented in 23.1%, 28.2%,
      and 16.6% of patients, respectively. CONCLUSION: Chemoimmunotherapy with BR is
      effective and safe in patients with relapsed CLL and has notable activity in
      fludarabine-refractory disease. Major but tolerable toxicities were
      myelosuppression and infections. These promising results encouraged us to
      initiate a further phase II trial evaluating the BR regimen in patients with
      previously untreated CLL.

PMID- 21844499
TI  - Chemotherapy-based treatment for castration-resistant prostate cancer.
AB  - Most men with metastatic prostate cancer respond to various types of androgen
      ablation but progress to castration-resistant disease. The TAX 327 and Southwest
      Oncology Group (SWOG) 99-16 clinical trials established docetaxel-based
      chemotherapy as preferred first-line treatment for most men with symptomatic
      metastatic castration-resistant prostate cancer (mCRPC). However, only about half
      receive benefit from docetaxel, and those who respond initially progress and
      eventually die of (or with) mCRPC. Both cellular mechanisms and the tumor
      microenvironment are implicated in the development of resistance to docetaxel.
      New agents are being evaluated for men with mCRPC, either as first-line treatment
      in combination with docetaxel, or in men progressing during or after treatment
      with docetaxel. Thus far, agents evaluated in phase III trials in combination
      with docetaxel have not improved outcome, including the vaccine GVAX, high-dose
      vitamin D (DN-101), and the antiangiogenic agent bevacizumab. In contrast,
      cabazitaxel, a taxane that is not cross-resistant to docetaxel, substantially
      improved the outcome of men progressing during or after treatment with docetaxel
      based chemotherapy when compared with mitoxantrone and prednisone. However,
      translation of benefit of cabazitaxel demonstrated in the TROPIC (Treatment of
      Hormone-Refractory Metastatic Prostate Cancer) trial into general oncologic
      practice will be challenging because this agent may cause serious toxicity. With
      the approval of less toxic hormonal agents (eg, abiraterone acetate) in the
      setting of docetaxel-resistant mCRPC, clinicians will have an opportunity to
      balance benefits and harms of new agents in an individual patient and may be able
      to use different agents in sequence.

PMID- 21844498
TI  - Androgen deprivation therapy and cardiovascular risk.
AB  - PURPOSE: The potential association between androgen deprivation therapy (ADT) and
      cardiovascular mortality (CVM) remains controversial. This study assessed
      mortality outcomes in a large national registry to further elucidate the
      association between treatment selection and cause of mortality. PATIENTS AND
      METHODS: A total of 7,248 men in the CaPSURE registry were analyzed. Treatment
      was categorized as local only, primary ADT monotherapy, local treatment plus ADT,
      and watchful waiting/active surveillance (WW/AS). Competing hazards survival
      analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and
      all-cause mortality. A propensity score-adjusted and a propensity-matched
      analysis were undertaken to adjust for imbalances in covariates among men
      receiving various treatments. RESULTS: Patients treated with ADT or WW/AS had a
      higher likelihood of PCSM than those treated with local therapy alone. Patients
      treated with primary ADT had an almost two-fold greater likelihood of CVM (HR,
      1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however,
      patients treated with WW/AS had a greater than two-fold increased risk of CVM
      (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of
      1,391 patients was unable to find a significant difference in CVM between those
      who did or did not receive ADT. CONCLUSION: Patients matched on propensity to
      receive ADT did not show an association between ADT and CVM. This suggests that
      potential unmeasured variables affecting treatment selection may confound the
      relationship between ADT use and cardiovascular risk. However, an association may
      yet exist, because the propensity score could not include all known risk factors
      for CVM.

PMID- 21844500
TI  - Prognostic factors influencing progression-free survival determined from a series
      of sporadic desmoid tumors: a wait-and-see policy according to tumor
      presentation.
AB  - PURPOSE: Desmoid tumors are mesenchymal fibroblastic/myofibroblastic
      proliferations with locoregional aggressiveness and high ability to recur after
      initial treatment. We present the results of the largest series of sporadic
      desmoid tumors ever published to determine the prognostic factors of these rare
      tumors. PATIENTS AND METHODS: Four hundred twenty-six patients with a desmoid
      tumor at diagnosis were included, and the following parameters were studied: age,
      sex, delay between first symptoms and diagnosis, tumor size, tumor site, previous
      history of surgery or trauma in the area of the primary tumor, surgical margins,
      and context of abdominal wall desmoids in women of child-bearing age during or
      shortly after pregnancy. We performed univariate and multivariate analysis for
      progression-free survival (PFS). RESULTS: In univariate analysis, age, tumor
      size, tumor site, and surgical margins (R2 v R0/R1) had a significant impact on
      PFS. PFS curves were not significantly different for microscopic assessment of
      surgical resection quality (R0 v R1). In multivariate analysis, age, tumor size,
      and tumor site had independent values. Three prognostic groups for PFS were
      defined on the basis of the number of independent unfavorable prognostic factors
      (0 or 1, 2, and 3). CONCLUSION: This study clearly demonstrates that there are
      different prognostic subgroups of desmoid tumors that could benefit from
      different therapeutic strategies, including a wait-and-see policy.

PMID- 21844501
TI  - When bad things happen to good studies.

PMID- 21844502
TI  - How do we define efficacy in comparing osteoclast-targeted agents in metastatic
      breast cancer?

PMID- 21844503
TI  - Population-based study of competing mortality in head and neck cancer.
AB  - PURPOSE: Patients with head and neck cancer (HNC) are at high risk of death
      resulting from noncancer causes and second malignancies (ie, competing
      mortality). Variation in competing mortality risk complicates individual
      treatment choices and design and interpretation of clinical studies. METHODS:
      Using the Surveillance, Epidemiology, and End Results registry, we identified
      34,568 patients with nonmetastatic squamous cell carcinoma of the head and neck
      diagnosed between 1994 and 2003. We developed a multivariable competing-risk
      regression model to stratify patients according to competing mortality risk and
      evaluate the impact of this risk on power loss in clinical studies. RESULTS: The
      5-year cumulative incidences of all-cause mortality, HNC-specific mortality, and
      competing mortality were 51.3% (95% CI, 50.8% to 51.9%), 23.8% (95% CI, 23.3% to
      24.2%), and 27.6% (95% CI, 26.8% to 28.3%), respectively. Factors associated with
      increased competing mortality were increasing age, male sex, black race,
      unmarried status, localized disease, higher socioeconomic status, nonsurgical
      treatment, and hypopharyngeal, nasopharyngeal, and oral cavity subsites. The 5
      year cumulative incidences of competing mortality for patients in low-, medium-,
      and high-risk score tertiles were 20.0% (95% CI, 18.8% to 21.3%), 27.7% (95% CI,
      26.3% to 29.1%), and 33.7% (95% CI, 32.2% to 35.2%), respectively. Compared with
      patients with low competing mortality risk, relative sample sizes required to
      show benefit of a treatment regarding all-cause mortality were 12% and 42% higher
      in the medium- and high-risk groups, respectively. CONCLUSION: Multiple factors
      affect risk of competing mortality among patients with HNC. Risk stratification
      would be useful to identify patients most likely to benefit from treatment
      intensification.

PMID- 21844504
TI  - Bevacizumab in combination with chemotherapy as first-line therapy in advanced
      gastric cancer: a randomized, double-blind, placebo-controlled phase III study.
AB  - PURPOSE: The Avastin in Gastric Cancer (AVAGAST) trial was a multinational,
      randomized, placebo-controlled trial designed to evaluate the efficacy of adding
      bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced
      gastric cancer. PATIENTS AND METHODS: Patients received bevacizumab 7.5 mg/kg or
      placebo followed by cisplatin 80 mg/m(2) on day 1 plus capecitabine 1,000 mg/m(2)
      twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients
      unable to take oral medications. Cisplatin was given for six cycles; capecitabine
      and bevacizumab were administered until disease progression or unacceptable
      toxicity. The primary end point was overall survival (OS). Log-rank test was used
      to test the OS difference. RESULTS: In all, 774 patients were enrolled; 387 were
      assigned to each treatment group (intention-to-treat population), and 517 deaths
      were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine
      cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard
      ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free
      survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037)
      and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved
      with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional
      differences in efficacy outcomes. The most common grade 3 to 5 adverse events
      were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo
      plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8%
      v 11%). No new bevacizumab-related safety signals were identified. CONCLUSION:
      Although AVAGAST did not reach its primary objective, adding bevacizumab to
      chemotherapy was associated with significant increases in progression-free
      survival and overall response rate in the first-line treatment of advanced
      gastric cancer.

PMID- 21844506
TI  - Randomized, double-blind, controlled trial of early endoscopic ultrasound-guided
      celiac plexus neurolysis to prevent pain progression in patients with newly
      diagnosed, painful, inoperable pancreatic cancer.
AB  - PURPOSE: Celiac plexus neurolysis (CPN) is currently used as salvage therapy for
      morphine-resistant pancreatic cancer pain. Endoscopic ultrasound-guided CPN (EUS
      CPN) can be performed early, at the time of EUS. We hypothesized that early EUS
      CPN would reduce pain and morphine consumption, increase quality of life (QOL),
      and prolong survival. PATIENTS AND METHODS: Patients were eligible if referred
      for EUS for suspected pancreatic cancer with related pain. If EUS and EUS-guided
      fine-needle aspiration cytology confirmed inoperable adenocarcinoma, patients
      were randomly assigned to early EUS-CPN or conventional pain management. Pain
      scores (7-point Likert scale), morphine equivalent consumption, and QOL scores
      (Digestive Disease Questionnaire-15) were assessed at 1 and 3 months. RESULTS:
      Five hundred eighty eligible patients were seen between April 2006 and December
      2008. Ninety-six patients were randomly assigned (48 patients per study arm).
      Pain relief was greater in the EUS-CPN group at 1 month and significantly greater
      at 3 months (difference in mean percent change in pain score = -28.9 [95% CI, 
      67.0 to 2.8], P = .09, and -60.7 [95% CI, -86.6 to -25.5], P = .01,
      respectively). Morphine consumption was similar in both groups at 1 month
      (difference in mean change in morphine consumption = -1.0 [95% CI, -47.7 to
      49.2], P = .99), but tended toward lower consumption at 3 months in the
      neurolysis group (difference in mean change in morphine consumption = -49.5 [95%
      CI, -127.5 to 7.0], P = .10). There was no effect on QOL or survival. CONCLUSION:
      Early EUS-CPN reduces pain and may moderate morphine consumption in patients with
      painful, inoperable pancreatic adenocarcinoma. EUS-CPN can be considered in all
      such patients at the time of diagnostic and staging EUS.

PMID- 21844507
TI  - Cardiovascular toxicity of androgen deprivation therapy: a new door opens.

PMID- 21844508
TI  - Reimbursement for advance care planning: why should intensivists care?

PMID- 21844505
TI  - Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front
      surgery and intensive timing radiation for malignant glioma.
AB  - PURPOSE: Despite aggressive therapies, median survival for malignant gliomas is
      less than 15 months. Patients with unmethylated O(6)-methylguanine-DNA
      methyltransferase (MGMT) fare worse, presumably because of temozolomide
      resistance. AdV-tk, an adenoviral vector containing the herpes simplex virus
      thymidine kinase gene, plus prodrug synergizes with surgery and
      chemoradiotherapy, kills tumor cells, has not shown MGMT dependency, and elicits
      an antitumor vaccine effect. PATIENTS AND METHODS: Patients with newly diagnosed
      malignant glioma received AdV-tk at 3 * 10(10), 1 * 10(11), or 3 * 10(11) vector
      particles (vp) via tumor bed injection at time of surgery followed by 14 days of
      valacyclovir. Radiation was initiated within 9 days after AdV-tk injection to
      overlap with AdV-tk activity. Temozolomide was administered after completing
      valacyclovir treatment. RESULTS: Accrual began December 2005 and was completed in
      13 months. Thirteen patients were enrolled and 12 completed therapy, three at
      dose levels 1 and 2 and six at dose level 3. There were no dose-limiting or
      significant added toxicities. One patient withdrew before completing prodrug
      because of an unrelated surgical complication. Survival at 2 years was 33% and at
      3 years was 25%. Patient-reported quality of life assessed with the Functional
      Assessment of Cancer Therapy-Brain (FACT-Br) was stable or improved after
      treatment. A significant CD3(+) T-cell infiltrate was found in four of four
      tumors analyzed after treatment. Three patients with MGMT unmethylated
      glioblastoma multiforme survived 6.5, 8.7, and 46.4 months. CONCLUSION: AdV-tk
      plus valacyclovir can be safely delivered with surgery and accelerated radiation
      in newly diagnosed malignant gliomas. Temozolomide did not prevent immune
      responses. Although not powered for efficacy, the survival and MGMT independence
      trends are encouraging. A phase II trial is ongoing.

PMID- 21844509
TI  - Are we ready to say that sex and race are key risk factors for COPD?

PMID- 21844510
TI  - The airway epithelium as a regulator of Th2 responses in asthma.

PMID- 21844511
TI  - Ventilator discontinuation: why are we still weaning?

PMID- 21844513
TI  - Baseline values and short serial change: a "road map" for a poor early outcome in
      idiopathic pulmonary fibrosis.

PMID- 21844512
TI  - Predicting mortality in patients with acute lung injury.

PMID- 21844514
TI  - Are obliterative pulmonary vascular lesions reversible?

PMID- 21844515
TI  - Altered autonomic nervous system function in sickle cell disease.

PMID- 21844516
TI  - Recommended reading from the hospital clinic (barcelona, Spain) pulmonary and
      critical care fellows: alvar agusti, program director.

PMID- 21844517
TI  - Susuk.

PMID- 21844518
TI  - Ventilator-associated pneumonia and cuff shape.

PMID- 21844519
TI  - "COPD-Lite": do you like the taste?

PMID- 21844520
TI  - Teaching NeuroImages: MRI changes of ictal cortical edema and tumor progression
      in a patient with astrocytoma.

PMID- 21844521
TI  - Teaching NeuroImages: Gravity reverses paradoxical herniation in the sinking
      brain syndrome.

PMID- 21844524
TI  - Glycine and its synaptic interactions: functional and clinical implications.

PMID- 21844526
TI  - Imaging findings in encephalocraniocutaneous lipomatosis.

PMID- 21844527
TI  - Child neurology: Brachial plexus birth injury: what every neurologist needs to
      know.
AB  - While most often transient, brachial plexus birth injury can cause permanent
      neurologic injury. The major risk factors for brachial plexus birth injury are
      fetal macrosomia and shoulder dystocia. The degree of injury to the brachial
      plexus should be determined in the neonatal nursery, as those infants with the
      most severe injury--root avulsion--should be referred early for surgical
      evaluation so that microsurgical repair of the plexus can occur by 3 months of
      life. Microsurgical repair options include nerve grafts and nerve transfers. All
      children with brachial plexus birth injury require ongoing physical and
      occupational therapy and close follow-up to monitor progress.

PMID- 21844528
TI  - Right brain: The blind spot.

PMID- 21844529
TI  - Association between weekend hospital presentation and stroke fatality.

PMID- 21844530
TI  - Teaching NeuroImages: Acquired Chiari malformation with syringohydromyelia caused
      by posterior fossa.

PMID- 21844531
TI  - Retraction. A clinical trial of pulpotomy vs. root canal therapy of mature
      molars. J Dent Res 89:1080-1085.

PMID- 21844532
TI  - Summaries for patients: causes and effects of delays in surgery for hip fracture.

PMID- 21844533
TI  - Summaries for patients: screening for bladder cancer: recommendations from the
      U.S. Preventive Services Task Force.

PMID- 21844534
TI  - Summaries for patients: management of chronic heart failure in adults: guidelines
      from the National Institute For Health and clinical excellence.

PMID- 21844535
TI  - ACP Journal Club. Review: angiotensin-receptor blockers do not increase adverse
      cardiovascular outcomes.

PMID- 21844536
TI  - ACP Journal Club. Calcium plus vitamin D was associated with increased
      cardiovascular risk in women not taking personal calcium supplements.

PMID- 21844537
TI  - ACP Journal Club. Review: oral drugs for type 2 diabetes, alone or in
      combination, have different relative benefits and harms for surrogate endpoints.

PMID- 21844538
TI  - ACP Journal Club. Review: high-calorie supplements increase weight in persons
      with dementia and feeding problems; no evidence exists for other outcomes.

PMID- 21844539
TI  - ACP Journal Club. Review: evidence for the effectiveness of acupuncture for pain
      is mixed.

PMID- 21844540
TI  - ACP Journal Club. Review: cardiac resynchronization reduces mortality and
      hospitalizations in patients with either more or less symptomatic HF.

PMID- 21844541
TI  - ACP Journal Club. Meta-analysis: high-dose statin pretreatment prevents
      periprocedural cardiac events in patients having PCI.

PMID- 21844542
TI  - ACP Journal Club. CABG added no benefit to medical therapy for preventing death
      in CAD with heart failure.

PMID- 21844543
TI  - ACP Journal Club. Review: stenting increases stroke but decreases periprocedural
      MI compared with endarterectomy in carotid artery disease.

PMID- 21844544
TI  - ACP Journal Club. An antimicrobial, antithrombotic lock solution reduced catheter
      related bloodstream infections in patients receiving dialysis.

PMID- 21844545
TI  - ACP Journal Club. Review: rosiglitazone increases risk for cardiovascular
      outcomes and mortality compared with pioglitazone in type 2 diabetes.

PMID- 21844546
TI  - ACP Journal Club. Active surveillance and use of barrier precautions did not
      reduce colonization and infection with MRSA and VRE in adult ICUs.

PMID- 21844547
TI  - Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan
      in the treatment of H1N1 influenza: a randomized trial.
AB  - BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan
      may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare
      the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating
      uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized,
      controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING:
      Eleven hospitals from 4 provinces in China. PATIENTS: 410 persons [corrected]
      aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza.
      INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction
      (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae),
      200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no
      intervention (control). Interventions and control were given for 5 days.
      MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes
      included symptom scores and viral shedding determined by using real-time reverse
      transcriptase polymerase chain reaction. RESULTS: Significant reductions in the
      estimated median time to fever resolution compared with the control group (26.0
      hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20%
      to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001),
      and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001).
      Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with
      oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The
      interventions and control did not differ in terms of decrease in symptom scores
      (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and
      vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus
      infection. Missing viral data precluded definitive conclusions about viral
      shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in
      combination, reduced time to fever resolution in patients with H1N1 influenza
      virus infection. These data suggest that maxingshigan-yinqiaosan may be used as
      an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING
      SOURCE: Beijing Science and Technology Project and Beijing Nova Program.

PMID- 21844548
TI  - Causes and effects of surgical delay in patients with hip fracture: a cohort
      study.
AB  - BACKGROUND: The clinical effect of surgical delay in older patients with hip
      fracture is controversial. Discrepancies among study findings may be due to
      confounding that is caused by the reason for the delay or a differential effect
      on patient risk subgroups. OBJECTIVE: To assess the effect of surgical delay on
      hospital outcomes according to the cause of delay. DESIGN: Prospective cohort
      study. SETTING: A hip fracture unit in a university hospital in Spain. PATIENTS:
      2250 consecutive elderly patients with hip fracture. MEASUREMENTS: Time to
      surgery, reasons for surgical delay, adjusted in-hospital death, and risk for
      complications. RESULTS: Median time to surgery was 72 hours. Lack of operating
      room availability (60.7%) and acute medical problems (33.1%) were the main
      reasons for delays longer than 48 hours. Overall, rates of hospital death and
      complications were 4.35% and 45.9%, respectively, but were 13.7% and 74.2% in
      clinically unstable patients. Longer delays were associated with higher mortality
      rates and rates of medical complications. After adjustment for age, dementia,
      chronic comorbid conditions, and functionality, this association did not persist
      for delays of 120 hours or less but did persist for delays longer than 120 hours
      (P = 0.002 for overall time effect on death and 0.002 for complications). The
      risks were attenuated after adjustment for the presence of acute medical
      conditions as the cause of the delay (P = 0.06 for time effect on mortality and
      0.31 on medical complications). Risk for urinary tract infection remained
      elevated (odds ratio, 1.54 [95% CI, 0.99 to 2.44]). No interaction between delay
      and age, dementia, or functional status was found. LIMITATION: This was a single
      center study without postdischarge follow-up. CONCLUSION: The reported
      association between late surgery and higher morbidity and mortality in patients
      with hip fracture is mostly explained by medical reasons for surgical delay,
      although some association between very delayed surgery and worse outcomes
      persists. PRIMARY FUNDING SOURCE: None.

PMID- 21844549
TI  - Comparative effectiveness of pain management interventions for hip fracture: a
      systematic review.
AB  - BACKGROUND: Pain management is integral to the management of hip fracture.
      PURPOSE: To review the benefits and harms of pharmacologic and nonpharmacologic
      interventions for managing pain after hip fracture. DATA SOURCES: 25 electronic
      databases (January 1990 to December 2010), gray literature, trial registries, and
      reference lists, with no language restrictions. STUDY SELECTION: Multiple
      reviewers independently and in duplicate screened 9357 citations to identify
      randomized, controlled trials (RCTs); nonrandomized, controlled trials (non
      RCTs); and cohort studies of pain management techniques in older adults after
      acute hip fracture. DATA EXTRACTION: Independent, duplicate data extraction and
      quality assessment were conducted, with discrepancies resolved by consensus or a
      third reviewer. Data extracted included study characteristics, inclusion and
      exclusion criteria, participant characteristics, interventions, and outcomes.
      DATA SYNTHESIS: 83 unique studies (64 RCTs, 5 non-RCTs, and 14 cohort studies)
      were included that addressed nerve blockade (n = 32), spinal anesthesia (n = 30),
      systemic analgesia (n = 3), traction (n = 11), multimodal pain management (n =
      2), neurostimulation (n = 2), rehabilitation (n = 1), and complementary and
      alternative medicine (n = 2). Overall, moderate evidence suggests that nerve
      blockades are effective for relieving acute pain and reducing delirium. Low-level
      evidence suggests that preoperative traction does not reduce acute pain. Evidence
      was insufficient on the benefits and harms of most interventions, including
      spinal anesthesia, systemic analgesia, multimodal pain management, acupressure,
      relaxation therapy, transcutaneous electrical neurostimulation, and physical
      therapy regimens, in managing acute pain. LIMITATIONS: No studies evaluated
      outcomes of chronic pain or exclusively examined participants from nursing homes
      or with cognitive impairment. Systemic analgesics (narcotics, nonsteroidal anti
      inflammatory drugs) were understudied during the search period. CONCLUSION: Nerve
      blockade seems to be effective in reducing acute pain after hip fracture. Sparse
      data preclude firm conclusions about the relative benefits or harms of many other
      pain management interventions for patients with hip fracture. PRIMARY FUNDING
      SOURCE: Agency for Healthcare Research and Quality.

PMID- 21844550
TI  - Screening for bladder cancer: U.S. Preventive Services Task Force recommendation
      statement.
AB  - DESCRIPTION: Update of the 2004 U.S. Preventive Services Task Force (USPSTF)
      recommendation statement on screening for bladder cancer. METHODS: The USPSTF
      performed a targeted literature search for new evidence on the benefits and harms
      of screening, the accuracy of primary care-feasible screening tests, and the
      benefits and harms of treatment. RECOMMENDATION: The USPSTF concludes that the
      current evidence is insufficient to assess the balance of benefits and harms of
      screening for bladder cancer in asymptomatic adults (I statement).

PMID- 21844551
TI  - Management of chronic heart failure in adults: synopsis of the National Institute
      For Health and clinical excellence guideline.
AB  - DESCRIPTION: The National Institute for Health and Clinical Excellence released
      its first clinical guideline on heart failure in 2003. This synopsis describes
      the update of that guideline, which was released in August 2010 and discusses the
      diagnosis, treatment, and monitoring of heart failure. METHODS: Guideline
      developers considered clinical evidence, health economic analyses, clinical
      expert opinion, and patient views. Systematic literature searches were performed,
      and an original decision model assessed the cost-effectiveness of serial
      measurement of serum natriuretic peptide to monitor patients with chronic heart
      failure. RECOMMENDATIONS: First, this guideline update describes the role of
      serum natriuretic peptide measurement, echocardiography, and specialist
      assessment in the diagnosis of heart failure. Second, it presents a pathway for
      pharmacologic treatment, rehabilitation, and pacing therapy (including
      implantable cardioverter-defibrillator and cardiac resynchronization therapy) for
      patients with heart failure and left ventricular systolic dysfunction and
      patients with heart failure and preserved ejection fraction. Finally, it explains
      the recommendation to monitor patients with heart failure by using serial
      measurement of serum natriuretic peptide.

PMID- 21844552
TI  - Ethics and the law: is there common ground on informed consent for disparities in
      hospital outcomes?
AB  - The association between procedure volume at institutions and outcomes of cancer
      surgeries has been widely published in the medical literature; discussed in the
      lay press; and, during the past 15 years, incorporated into quality improvement
      endeavors. In certain cases, institutional volume has become a proxy for quality.
      Despite the vast amount of retrospective data on this topic, physicians generally
      have been unsure how to approach the information and interpret it for their
      patients. Even more challenging to some physicians has been deciding whether the
      data oblige them to either direct patients with cancer to high-volume centers for
      care or discuss the data with these patients as part of informed consent. An
      additional challenge is that physicians must understand laws related to these
      issues and that these laws are unclear. This article reviews the ethical
      arguments for including disparities in hospital outcomes as part of informed
      consent and examines whether legal precedent can shed light on this debate.

PMID- 21844553
TI  - Hip fracture: a complex illness among complex patients.

PMID- 21844555
TI  - On being observed.

PMID- 21844554
TI  - The evolving story of guidelines and health care: does being NICE help?

PMID- 21844556
TI  - The doctor I want to be.

PMID- 21844557
TI  - Surveillance for hepatocellular carcinoma.

PMID- 21844558
TI  - Surveillance for hepatocellular carcinoma.

PMID- 21844559
TI  - Screening for osteoporosis: U.S. Preventive Services Task Force recommendation
      statement.

PMID- 21844560
TI  - Surveillance for hepatocellular carcinoma.

PMID- 21844561
TI  - Screening for osteoporosis: U.S. Preventive Services Task Force recommendation
      statement.

PMID- 21844562
TI  - Combined oral and intranasal corticosteroid therapy for nasal polyps.

PMID- 21844563
TI  - Diagnostic performance of low-radiation-dose coronary computed tomography
      angiography.

PMID- 21844564
TI  - Significant dose differences in donepezil purchased from the United States and
      Canada.

PMID- 21844565
TI  - SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non
      Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target.
AB  - B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is
      characterized by defective apoptosis. We found that the SET oncoprotein, a potent
      inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed
      in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In
      CLL, increased levels of SET correlated significantly with disease severity
      (shorter time to treatment and overall survival). We developed SET antagonist
      peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1
      expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro.
      In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET
      antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These
      data demonstrate that SET is a new treatment target in B-cell malignancies and
      that SET antagonists represent novel agents for treatment of CLL and NHL.

PMID- 21844566
TI  - Leukocyte integrin activation mediates transient neutropenia after G-CSF
      administration.
AB  - After administration of granulocyte colony-stimulating factor (G-CSF), there is a
      marked, albeit transient, drop in circulating neutrophils. To determine the role
      of leukocyte integrins in this disappearance, a dog having canine leukocyte
      adhesion deficiency (CLAD) or CLAD dogs who had undergone gene correction either
      by matched littermate allogeneic transplant or autologous gene therapy were
      evaluated. Shortly after G-CSF administration, a dramatic, yet transient,
      neutropenia was observed in the control littermates. This neutropenia was not as
      marked in the CLAD dogs. In all instances, it was CD18(+) neutrophils that
      preferentially egressed from the circulation. The association of CD18 with this
      rapid loss suggested leukocyte integrin activation after G-CSF administration. To
      determine the activation status of the integrin, a monoclonal antibody
      recognizing the activated alpha-subunit cation binding domain (mAb24) was used to
      evaluate human leukocytes after G-CSF administration. Mirroring the dramatic
      decrease in circulating neutrophil numbers, there was a dramatic and specific
      increase in the activation of the alpha-subunit after G-CSF expression on
      polymorphonuclear leukocytes. This activation, like the drop in neutrophil count,
      was transient. These results demonstrate that the leukocyte integrin on
      circulating neutrophils is transiently activated after G-CSF administration and
      mediates the transient neutropenia observed after G-CSF administration.

PMID- 21844568
TI  - Diseases and disorders associated with excess body weight.
AB  - Excess body weight is a very serious problem, especially in North America and
      Europe. It has been referred to as a "pandemic" since it has progressively
      increased over the past several decades. Moreover, excess body weight
      significantly increases the risk of numerous diseases and clinical disorders,
      including all-cause mortality, coronary and cerebrovascular diseases, various
      cancers, type 2 diabetes mellitus, hypertension, liver disease and asthma, as
      well as psychopathology, among others. Unfortunately, overweight and obesity are
      now common in both young children and adolescents. Although the causes of excess
      body weight are multi-factorial, the most important factors are excess caloric
      intake coupled with limited energy expenditure. Therefore, lifestyle modification
      can significantly reduce the risk of morbidity and mortality and thereby increase
      longevity and improve the quality of life.

PMID- 21844567
TI  - HDM-2 inhibition suppresses expression of ribonucleotide reductase subunit M2,
      and synergistically enhances gemcitabine-induced cytotoxicity in mantle cell
      lymphoma.
AB  - Mantle cell lymphoma (MCL) usually responds well to initial therapy but is prone
      to relapses with chemoresistant disease, indicating the need for novel
      therapeutic approaches. Inhibition of the p53 E3 ligase human homolog of the
      murine double minute protein-2 (HDM-2) with MI-63 has been validated as one such
      strategy in wild-type (wt) p53 models, and our genomic and proteomic analyses
      demonstrated that MI-63 suppressed the expression of the ribonucleotide reductase
      (RNR) subunit M2 (RRM2). This effect occurred in association with induction of
      p21 and cell-cycle arrest at G(1)/S and prompted us to examine combinations with
      the RNR inhibitor 2',2'-difluoro-2'-deoxycytidine (gemcitabine). The regimen of
      MI-63-gemcitabine induced enhanced, synergistic antiproliferative, and
      proapoptotic effects in wtp53 MCL cell lines. Addition of exogenous dNTPs
      reversed this effect, whereas shRNA-mediated inhibition of RRM2 was sufficient to
      induce synergy with gemcitabine. Combination therapy of MCL murine xenografts
      with gemcitabine and MI-219, the in vivo analog of MI-63, resulted in enhanced
      antitumor activity. Finally, synergy was seen with MI-63-gemcitabine in primary
      patient samples that were found to express high levels of RRM2 compared with MCL
      cell lines. These findings provide a framework for translation of the rational
      combination of an HDM-2 and RNR inhibitor to the clinic for patients with
      relapsed wtp53 MCL.

PMID- 21844569
TI  - Grading ductal carcinoma in situ of the breast using an automated proliferation
      index.
AB  - Tumor grade, size and margin status are the most significant factors in
      predicting the behavior of ductal carcinoma in-situ (DCIS). The inclusion of
      necrosis and nuclear grade in the grading of DCIS has demonstrated a fair but
      suboptimal agreement between pathologists. The grading of DCIS was studied and
      compared to the Van Nuys (VN) system, by using our newly proposed unifying
      "nuclear grade + proliferation index (N+P) grading system for invasive
      carcinomas. 162 DCIS tumors were studied including 49 VN I, 31 VN II, and 82 VN
      III cases. The VN and N+P systems were compared with each other and correlated
      with tumor size, ER, PR, p53, Her-2, EGFR, Bcl-2, p27 and p21 status. The two
      systems demonstrated similar frequencies for the different grades and an
      agreement with each other for all of the biomarkers studied. The greatest
      difference between the two systems was observed for those tumors initially
      classified as VN II (94% being down-graded to N+P I) and VN III (80% being down
      graded to N+P II). These results suggest that the N+P system, combining nuclear
      grade with automated MIB-1 count, is a potentially valid and reproducible grading
      system for both non-invasive and invasive mammary carcinomas. It is automated,
      less subjective in assessing mitotic activity and necrosis and correlates with
      other prognostic biomarkers.

PMID- 21844570
TI  - Point-of-care testing for B-type natriuretic peptide in premature neonates with
      patent ductus arteriosus.
AB  - Patent ductus arteriosus (PDA) is highly prevalent in pre-term neonates (PTN) and
      has been recognized as a neonatal co-morbidity. The purpose of this study was to
      determine if levels of brain (or B-type) natriuretic peptide (BNP), a peptide
      secreted by ventricular myocytes in response to volume or pressure overload,
      correlate with the size of the PDA. In a prospective design, 52 PTN (no PDA:
      n=24; PDA: n=28) were studied after obtaining parental consent. Those with
      genetic anomalies and congenital heart disease, except for PDA and patent foramen
      ovale, were excluded. Echocardiographic estimates of the diameters of the PDA (or
      absence of PDA) were made concurrently with capillary blood collection for BNP
      assay. BNP levels in samples from PTN without PDA were 23.6 ng/L (median); 13.1
      to 32.3 ng/L (IQR); initial samples (between days 3 and 7 of life) with small PDA
      (n=11), median 66.1 ng/L; 55.5 to 85.3 ng/L (IQR); with moderate PDA (n=6) median
      284 ng/L; 204 to 622 ng/L (IQR); and with large PDA (n=11) 2410 ng/L median; 420
      to 2770 ng/L (IQR). (p< 0.0001 for ANOVA; groupwise: p<0.05 for both no PDA vs.
      moderate and large PDA); Trend analysis suggested a strong association of BNP
      with size of PDA (p<0.001). Of 17 subjects with moderate to large PDA, pre and
      post-treatment (Ibuprofen; per standard protocol) data were obtained on 12
      subjects. Pre-treatment BNP ranged from 111 to 5000 ng/L; post-treatment BNP
      decreased to 5.0 to 262 ng/L (p = 0.0005). Estimates of decision levels for
      treatment were made by examining dichotomized groups, i.e., no-to-small vs.
      moderate-to-large and using receiver-operator characteristic (ROC) curve analysis
      yielding a value of 123 ng/L. BNP may obviate repeated echocardiography as follow
      up after treatment, or to monitor future course of respiratory distress secondary
      to PDA in PTN.

PMID- 21844571
TI  - Underestimation of recipient DNA in bone marrow by post-transplant chimerism
      analyses using DNA extracted from EDTA-collected aspirate samples in pediatric
      acute myeloid leukemia.
AB  - GOALS: Chimerism analysis (CA) is essential for post-transplant surveillance. DNA
      from bone marrow (BM) aspirates drawn into EDTA specimen tubes (EDTA-BM) is
      widely used for CA. Since EDTA-BM is subject to peripheral dilution, however, DNA
      from aspirate particle smears (PS-BM) might better represent BM chimerism status.
      In this regard, we evaluated the influence of BM sources on CA. PROCEDURES: Study
      subjects were consecutive pediatric AML patients who had experienced relapse
      after allogeneic stem cell transplantation with the interval between CA before
      relapse (pre-relapse) and at relapse <6 months. We compared chimerism status at
      the 2 time-points by fluorescence PCR on STR markers using EDTA-BM vs PS-BM.
      RESULTS: Eight patients were eligible for this study. The recipient DNA (%R) from
      EDTA-BM was 0% at pre-relapse in all except 2 with 1.6% and 1.3%, while %R using
      PS-BM revealed mixed chimerism in all 8, %R ranging 1.6-13.2% (median 3.75%). The
      %R from EDTA-BM was 0.9-79.3% at relapse (29.15%), while %R from PS-BM was 3.8
      86.6% (60.15%). The difference of %R (Delta%R), %R[PS-BM]-% R[EDTA-BM], was
      median 3.15% (1.6-13.2%) at pre-relapse and median 12.1% (2.1-60.7%) at relapse.
      CONCLUSIONS: Our study showed CA using EDTA-BM significantly underestimated %R.
      Our observation might have a ramification to other quantitative workup in
      hematologic malignancy.

PMID- 21844572
TI  - Flow cytometric detection of neutrophil-associated immunoglobulin in patients
      with or without neutropenia and establishment of the reference interval.
AB  - We measured neutrophil-associated immunoglobulin (NAIg) levels using flow
      cytometry to establish the reference interval for NAIg and to estimate NAIg in
      patients with or without neutropenia. Peripheral blood from 152 individuals was
      analyzed for NAIg detection by flow cytometry. Using fluorescescent-conjugated
      anti-CD10 monoclonal antibody and anti-human immunoglobulins, proportions of
      NAIgG, NAIgA, and NAIgM bound to neutrophils were measured. Reference intervals
      for NAIg were set as NAIgG <2.6%, NAIgA <3.2%, and NAIgM <3.4%, representing the
      95th percentile of data from 40 healthy individuals. 63 patients with neutropenia
      showed positivities of 49.2% (31/63) for NAIgG, 50.0% (19/38) for NAIgA, and
      42.9% for (27/63) NAIgM. The proportion of NAIgA-bound neutrophils was higher in
      females (median 10.7% vs 3.0%, P=0.024), and NAIgA positivity rates were
      increased in patients aged less than 10 years (83.3%, P=0.043). NAIg was
      associated with the severity of neutropenia. In particular, NAIgM levels were
      significantly increased in patients with severe neutropenia (P=0.019). In
      addition, NAIg was commonly detected in patients with autoimmune diseases, solid
      organ tumors, hematologic disorders, and lymphoma. Flow cytometry permitted rapid
      detection of NAIg in small samples. Using this method, and using the reference
      intervals defined herein, patients with neutropenia or adverse transfusion
      reactions may be evaluated in a clinically relevant manner.

PMID- 21844573
TI  - Transient dyslipidemia mimicking the plasma lipid profile of Tangier disease in a
      diabetic patient with gram negative sepsis.
AB  - Tangier disease is a rare genetic disorder of lipid metabolism characterized by
      low concentrations of plasma high density lipoprotein (HDL) and low density
      lipoprotein (LDL) cholesterol with normal or elevated levels of triglycerides. In
      this case report we describe a patient with diabetes who experienced an episode
      of urosepsis with a plasma lipid profile resembling Tangier disease. Experimental
      evidence in the literature suggests that similar lipid changes may occur due to
      cytokines released during sepsis. Clinicians should be aware of these changes to
      avoid misdiagnosis of lipid disorders.

PMID- 21844574
TI  - Expression of B7-homolog 1 in Polymyositis.
AB  - OBJECTIVES: Costimulatory molecules are increasingly recognized as crucial for
      stimulation and/ or inhibition of immune responses. The present study was
      undertaken to examine the expression and functional relevance of B7-homolog 1 (B7
      H1) attributed significant immunoregulatory functions in polymyositis in vivo.
      METHODS: 43 muscle biopsy specimens obtained from patients with polymyositis, 26
      cases with limb girdle muscular dystrophies (LGMD) 2B and 21 normal muscle
      samples were analyzed by immunohistochemistry for B7-H1 expression. The clinical
      and histopathologic data were analyzed. RESULTS: B7-H1 was not detectable on
      normal muscle fibers and rarely detectable from patients with LGMD-2B. In
      contrast, its expression was markedly increased on muscle fibers from patients
      with polymyositis, even after short-term immunosuppressive treatment. Positive
      staining mainly localized at the surface of the muscle tissue, rarely in the
      cytoplasm, focused in areas where inflammatory cells lay in close apposition to
      damaged, necrotic or degenerative muscle fibers. The expression of B7-H1 was
      correlated to the degrees of muscular necrosis and clinical muscular strength.
      CONCLUSION: Our results demonstrate that human muscle cells express B7-H1 in
      polymyositis. The muscle-related expression of B7-H1 may be helpful in the
      diagnosis of polymyositis and might be an indicator of prognosis of polymyositis.

PMID- 21844575
TI  - Identification and characterization of OXA-48 producing, carbapenem-resistant
      Enterobacteriaceae isolates in Turkey.
AB  - Carbapenem resistance in Enterobacteriaceae isolates has been reported from
      Turkey and is most often mediated by OXA-48 type carbapenemases. We report the
      identification and characterization of four carbapenem-resistant isolates (three
      Klebsiella pneumoniae and one Escherichia coli) among 515 clinical
      Enterobacteriaceae isolates collected during a 7-month study period in Ankara,
      Turkey. The four isolates were recovered from blood and urine specimens in
      patients with varied clinical manifestations. They had distinct pulsed-field gel
      electrophoresis patterns and harbored a variety of beta-lactamases including
      bla(TEM-1), bla(SHV-12) genes, bla(SHV-11), and/or bla(CTX-M-15). PCR and
      sequencing analysis revealed that the bla(OXA-48) gene was present in all four
      isolates. Our data indicated that the OXA-48-type carbapenemase was the only
      mechanism for carbapenem resistance in our hospital.

PMID- 21844576
TI  - Three Korean patients with maple syrup urine disease: four novel mutations in the
      BCKDHA gene.
AB  - Maple syrup urine disease (MSUD) is a rare, autosomal recessive disorder of
      branched-chain amino acid (BCAA) metabolism caused by dysfunction of the
      multienzyme branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. Although
      a few cases of MSUD have been reported in the Korean population, the genetic
      background of MSUD is not well understood. In this study, we investigated three
      newborn males who were diagnosed with MSUD using a standard newborn screening
      test and amino acid analysis. We screened all coding regions of the BCKDHA,
      BCKDHB and DBT genes for abnormalities using direct sequencing. Changes in these
      genes are associated with MSUD. For one patient with complex deletion/duplication
      mutations, we also performed TOPO TA cloning sequencing. Amino acid analysis
      showed elevated levels of all branched chain amino acids (BCAAs) in all patients.
      Three patients were either homozygous or compound heterozygous for the BCKDHA
      mutations. Patient 1 was homozygous for c.1036C>T (p.R346C); patient 2 was
      heterozygous, with c.632C>T (p.T211M) and c.659C>T (p.A220V); and patient 3 had
      c.1204_1209dupAAACCC (p.L402_P403dup) and c.1280_1282delTGG (p.L427_A428delinsP).
      Among these mutations, c.1036C>T, c.632C>T, c.1204_1209dup and c.1280_1282del
      were novel. These patients had no mutations in either the BCKDHB or the DBT gene.
      Although this study included only three patients, the five different mutations in
      these patients may indicate mutational heterogeneity in Korean patients with
      MSUD. In addition, the BCHDHA gene may present a primary target for clinical
      genetic analysis. To the best of our knowledge, this is the first report of
      genetically confirmed MSUD in Korea.

PMID- 21844577
TI  - Papillary tumor of the pineal region: two case studies and a review of the
      literature.
AB  - Papillary tumor of the pineal region (PTPR) is a newly recognized distinct entity
      in the 2007 World Health Organization nomenclature. This tumor is characterized
      by epithelial-appearing areas with papillary features and more densely cellular
      areas that often display ependymal-like differentiation. Ultrastructurally, this
      rare neuroepithelial tumor possesses neuroendocrine, secretory, and ependymal
      organelles that likely originate from the subcommissural organ (SCO) near the
      aqueduct of Sylvius. To date, approximately fifty-seven described cases worldwide
      have been recognized, with ages ranging from 5 years to 66 years (mean age=32
      years). Clinical presentation most often includes headache and obstructive
      hydrocephalus. The tumor, which is well circumscribed, may be cystic and
      radiographically is often considered to be consistent with the findings of a
      pineocytoma. Microscopic evaluation often demonstrates a lesion with papillary
      areas lined by epithelioid tumor cells with eosinophilic cytoplasm and more
      cellular areas with cells exhibiting clear or vacuolated cytoplasm. Perivascular
      and true rosettes may be identified. Distinctive immunohistochemical features
      including reactivity for keratins (AE1/AE3, CAM 5.2, CK18) and only focal GFAP
      staining help distinguish this neoplasm from an ependymoma. The relative paucity
      of data compiled for this tumor makes giving an accurate diagnosis and prognosis
      a daunting task. We discuss two additional cases of PTPR that presented to us
      within a three-month span in order to more fully elucidate the possible
      presentations of this rare entity. Furthermore, we examine now 59 reported cases
      of PTPR in order to review the current diagnostic and treatment modalities in
      addition to exploring emerging research encompassing this unusual neoplasm.

PMID- 21844578
TI  - Two novel PEX1 mutations in a patient with Zellweger syndrome: the first Korean
      case confirmed by biochemical, and molecular evidence.
AB  - Peroxisome biogenesis disorders (PBD) represent a spectrum of genetic disorders
      characterized by impaired peroxisome assembly. Zellweger syndrome (ZS) is the
      most severe form of PBD and is characterized by craniofacial abnormalities,
      severe hypotonia, neonatal seizures, ocular abnormalities, psychomotor
      retardation, hepatomegaly and increased levels of very long chain fatty acids
      (VLCFA). The most common mutation associated with the PBD is PEX1. Here, the
      first Korean patient with ZS confirmed by clinical, biochemical, and molecular
      findings is reported. Two novel mutations of the PEX1 gene were identified in the
      patient with ZS. The patient was a compound heterozygote for c.2034_2035delCA and
      c.2845C>T mutations of the PEX1 gene. Both mutations are novel findings and were
      inherited from the patient's parents. In summary, here the first Korean case of
      ZS is reported that was confirmed by two novel mutations of the PEX1 gene.

PMID- 21844579
TI  - The utility of fluorescence in situ hybridization (FISH) analysis in diagnosing
      graft versus host disease following orthotopic liver transplant.
AB  - Graft versus host disease (GVHD) following liver transplant occurs in 0.1-2% of
      patients and portends a poor prognosis. Affected organs include skin, the
      gastrointestinal tract and bone marrow. We present the case of a 61 year old
      female who developed skin rash and pancytopenia following sex-mismatched second
      liver transplant for autoimmune hepatitis. Initial skin biopsies revealed
      vacuolar interface change, keratinocyte necrosis and a mild mononuclear
      superficial perivascular infiltrate. The bone marrow was markedly hypocellular
      with scattered CD8 positive T lymphocytes. FISH analysis revealed chimerism with
      the presence of male donor cells in the skin and bone marrow biopsies. This case
      illustrates the diagnostic utility of FISH in detecting the presence of donor
      derived cells in tissues affected by GVHD.

PMID- 21844580
TI  - CKIT mutation in therapy-related acute myeloid leukemia with MLLT3/MLL chimeric
      transcript from t(9;11)(p22;q23).
AB  - Gain-of-function mutations of the CKIT gene have been reported to specifically
      occur in core-binding factor (CBF) acute myeloid leukemia (AML) with a poor
      prognostic implication. Here we report a case of therapy-related AML with
      t(9;11)(p22;q23) who had CKIT mutation. A 48-year-old woman with breast cancer
      received partial mastectomy followed by 6 cycles of adjuvant chemotherapy and
      radiation therapy. At 28 months from the diagnosis of breast cancer, she was
      diagnosed as having AML with blasts 81% in bone marrow. Cytogenetic analysis
      revealed t(9;11)(p22;q23), and FISH showed 96.5% of MLL break-apart signals. RT
      PCR study revealed MLL(11q23)/MLLT3(9p22) chimeric transcript. FLT3-ITD and NPM1
      mutations were both negative. Unexpectedly, mutation analyses for CKIT identified
      D816Y mutation. The patient received induction chemotherapy and achieved complete
      remission at 1 month. To the best of our knowledge, this is the first report on
      CKIT mutation in therapy-related AML with MLL rearrangement.

PMID- 21844581
TI  - A novel PHKA2 gross deletion mutation in a Korean patient with X-linked liver
      glycogenosis type I.
AB  - X-linked liver glycogenosis (XLG) is caused by a mutation in the PHKA2 gene which
      encodes the alpha subunit of phosphorylase kinase (PHK). Although XLG is not a
      rare disease, there have been no reports of PHKA2 mutations in Koreans. A 5-year
      old boy presented with easy fatigability and hepatomegaly. Liver enzymes were
      increased and liver histology revealed deposition of glycogen. The PHK activity
      was markedly decreased compared to control. No amplification was observed at exon
      8 of the PHKA2 gene, as a result of the deletion of exon 8. Sequence analysis
      revealed a hemizygous deletion in the region of exon 8
      (c.717+781_864+225del1626). The patient was diagnosed as having XLG I. To the
      best of our knowledge, this is the first report of XLG I in Koreans.

PMID- 21844582
TI  - A note from history: microscopic contributions of pioneer pathologists.

PMID- 21844583
TI  - Lipid droplets: size matters.
AB  - The lipid droplet (LD), an organelle that exists ubiquitously in various
      organisms, from bacteria to mammals, has attracted much attention from both
      medical and cell biology fields. The LD in white adipocytes is often treated as
      the prototype LD, but is rather a special example, considering that its size,
      intracellular localization and molecular composition are vastly different from
      those of non-adipocyte LDs. These differences confer distinct properties on
      adipocyte and non-adipocyte LDs. In this article, we address the current
      understanding of LDs by discussing the differences between adipocyte and non
      adipocyte LDs.

PMID- 21844584
TI  - The cell cycle, including the mitotic cycle and organelle division cycles, as
      revealed by cytological observations.
AB  - It is generally believed that the cell cycle consists essentially of the mitotic
      cycle, which involves mitosis and cytokinesis. These processes are becoming
      increasingly well understood at the molecular level. However, successful cell
      reproduction requires duplication and segregation (inheritance) of all of the
      cellular contents, including not only the cell-nuclear genome but also
      intracellular organelles. Eukaryotic cells contain at least three types of double
      membrane-bounded organelles (cell nucleus, mitochondria and plastids), four types
      of single membrane-bounded organelles (endoplasmic reticulum, Golgi apparatus,
      lysosomes and microbodies) and the cytoskeleton, which comprises tubulin-based
      structures (including microtubules, centrosome and spindle) and actin
      microfilaments. These membrane-bounded organelles cannot be formed de novo and
      daughter organelles must be inherited from parent organelles during cell cycle.
      Regulation of organelle division and its coordination with the progression of the
      cell cycle involves a sequence of events that are subjected to precise spatio
      temporal control. Considering that the cells of higher animals and plants contain
      many organelles which tend to behave somewhat randomly, there is little
      information concerning the division and inheritance of these double- and single
      membrane-bounded organelles during the cell cycle. Here, we summarize the current
      cytological and morphological knowledge of the cell cycle, including the division
      cycles of seven membrane-bounded and some non-membrane-bounded organelles. The
      underlying mechanisms and the biological relevance of these processes are
      discussed, particularly with respect to cells of the primitive alga
      Cyanidioschyzon merolae that have a minimum of organelles. We discuss unsolved
      problems and future perspectives opened by recent studies.

PMID- 21844585
TI  - Insights into the molecular organization of the neuron by cryo-electron
      tomography.
AB  - Despite great progress in the identification and characterization of the key
      molecular players in neuronal function, remarkably little is known about their
      supramolecular organization. Cryo-electron tomography (cryo-ET), providing three
      dimensional views of the molecular components of the cell in their native, fully
      hydrated environment, is uniquely positioned to elucidate the native architecture
      of the molecular machinery of the neuron. In our laboratory, we employ cryo-ET to
      study neuronal morphology in a variety of experimental systems and develop
      methods to extract quantitative and functional information from tomographic data.
      This approach has allowed us to shed light onto the intricate organization of the
      molecules of the synaptic cleft and the presynaptic cytomatrix, providing
      evidence for their functional roles. Also, cryo-ET of cultured neurons is
      beginning to open new perspectives on neuronal ultrastructure and the
      architecture of synaptic complexes in situ. Here, we will review these findings
      and discuss future directions towards the elucidation of the molecular landscape
      of the neuron.

PMID- 21844586
TI  - Electron crystallography for structural and functional studies of membrane
      proteins.
AB  - Membrane proteins are important research targets for basic biological sciences
      and drug design, but studies of their structure and function are considered
      difficult to perform. Studies of membrane structures have been greatly
      facilitated by technological and instrumental advancements in electron microscopy
      together with methodological advancements in biology. Electron crystallography is
      especially useful in studying the structure and function of membrane proteins.
      Electron crystallography is now an established method of analyzing the structures
      of membrane proteins in lipid bilayers, which resembles their natural biological
      environment. To better understand the neural system function from a structural
      point of view, we developed the cryo-electron microscope with a helium-cooled
      specimen stage, which allows for analysis of the structures of membrane proteins
      at a resolution higher than 3 A. This review introduces recent instrumental
      advances in cryo-electron microscopy and presents some examples of structure
      analyses of membrane proteins, such as bacteriorhodopsin, water channels and gap
      junction channels. This review has two objectives: first, to provide a personal
      historical background to describe how we came to develop the cryo-electron
      microscope and second, to discuss some of the technology required for the
      structural analysis of membrane proteins based on cryo-electron microscopy.

PMID- 21844587
TI  - From electron energy-loss spectroscopy to multi-dimensional and multi-signal
      electron microscopy.
AB  - This review intends to illustrate how electron energy-loss spectroscopy (EELS)
      techniques in the electron microscope column have evolved over the past 60 years.
      Beginning as a physicist tool to measure basic excitations in solid thin foils,
      EELS techniques have gradually become essential for analytical purposes, nowadays
      pushed to the identification of individual atoms and their bonding states. The
      intimate combination of highly performing techniques with quite efficient
      computational tools for data processing and ab initio modeling has opened the way
      to a broad range of novel imaging modes with potential impact on many different
      fields. The combination of Angstrom-level spatial resolution with an energy
      resolution down to a few tenths of an electron volt in the core-loss spectral
      domain has paved the way to atomic-resolved elemental and bonding maps across
      interfaces and nanostructures. In the low-energy range, improved energy
      resolution has been quite efficient in recording surface plasmon maps and from
      them electromagnetic maps across the visible electron microscopy (EM) domain,
      thus bringing a new view to nanophotonics studies. Recently, spectrum imaging of
      the emitted photons under the primary electron beam and the spectacular
      introduction of time-resolved techniques down to the femtosecond time domain,
      have become innovative keys for the development and use of a brand new multi
      dimensional and multi-signal electron microscopy.

PMID- 21844588
TI  - Grain boundary atomic structures and light-element visualization in ceramics:
      combination of Cs-corrected scanning transmission electron microscopy and first
      principles calculations.
AB  - Grain boundaries and interfaces of crystals have peculiar electronic structures,
      caused by the disorder in periodicity, providing the functional properties, which
      cannot be observed in a perfect crystal. In the vicinity of the grain boundaries
      and interfaces, dopants or impurities are often segregated, and they play a
      crucial role in deciding the properties of a material. Spherical aberration (Cs)
      corrected scanning transmission electron microscopy (STEM), allowing the
      formation of sub-angstrom-sized electron probes, can directly observe grain
      boundary-segregated dopants. On the other hand, ceramic materials are composed of
      light elements, and these light elements also play an important role in the
      properties of ceramic materials. Recently, annular bright-field (ABF)-STEM
      imaging has been proposed, which is now known to be a very powerful technique in
      producing images showing both light- and heavy-element columns simultaneously. In
      this review, the atomic structure determination of ceramic grain boundaries and
      direct observation of grain boundary-segregated dopants and light elements in
      ceramics were shown to combine with the theoretical calculations. Examples are
      demonstrated for well-defined grain boundaries in rare earth-doped Al(2)O(3) and
      ZnO ceramics, CeO(2) and SrTiO(3) grain boundary, lithium battery materials and
      metal hydride, which were characterized by Cs-corrected high-angle annular dark
      field and ABF-STEM. It is concluded that the combination of STEM characterization
      and first-principles calculation is very useful in interpreting the structural
      information and in understanding the origin of the properties in various
      ceramics.

PMID- 21844589
TI  - Topics in recent studies with high-voltage electron microscopes.
AB  - In this article, topics in recent studies with high-voltage electron microscopes
      (HVEMs) are reviewed. High-voltage electron microscopy possesses a number of
      advantages that cannot be afforded by conventional electron microscopy, thus
      providing a unique microscopy technique in both materials science and biological
      science. One of these advantages is the capability of continuously observing
      phenomena using a variety of electron microscopy techniques simultaneously with
      the introduction of the displacement of atoms from lattice points. This has
      enabled in-depth studies on such fundamental subjects as the crystalline-to
      amorphous-to-crystalline transition, the motion properties of point defects and
      the one-dimensional diffusion of dislocation loops. Electron tomography studies
      using HVEMs take advantage of the large observable thickness of a specimen. In
      addition, by combining different advantages, a number of advanced applications in
      materials science have been carried out, including analyses of the atomic
      structure of a reduction-induced reconstructed surface and the atomic mechanism
      behind the self-catalytic vapor-liquid-solid growth of an oxide nanowire. As long
      as excellent and invaluable studies that cannot be carried out without HVEMs
      appear in succession, it is necessary to make the utmost efforts to improve these
      microscopes.

PMID- 21844590
TI  - Atom world based on nano-forces: 25 years of atomic force microscopy.
AB  - Scanning tunneling microscopy (STM) has opened up the new nanoworlds of scanning
      probe microscopy. STM is the first-generation atomic tool that can image,
      evaluate and manipulate individual atoms and consequently can create
      nanostructures by true bottom-up methods based on atom-by-atom manipulation.
      Atomic force microscopy is a second-generation atomic tool that has followed the
      footsteps of STM, and which is now opening doors to a new atom world based on
      using nanoscale forces.

PMID- 21844591
TI  - New views of materials through aberration-corrected scanning transmission
      electron microscopy.
AB  - The successful correction of third-order and, more recently, fifth-order
      aberrations has enormously enhanced the capabilities of the scanning transmission
      electron microscope (STEM), by not only achieving record resolution, but also
      allowing near 100% efficiency for electron energy loss spectroscopy, and higher
      currents for two-dimensional spectrum imaging. These advances have meant that the
      intrinsic advantages of the STEM, incoherent imaging and simultaneous collection
      of multiple complementary images can now give new insights into many areas of
      materials physics. Here, we review a number of examples, mostly from the field of
      complex oxides, and look towards new directions for the future.

PMID- 21844592
TI  - Electron holography study of electric field variations.
AB  - This paper presents a review of the recent electron holography studies on
      electric field variation that have been carried out using multifunctional
      specimen holders. In addition to the standard inner potential analysis, studies
      on electric field variations around field emission tips have been carried out.
      The electric field variations caused by ballistic emission in the case of a field
      emitter made of a TaSi(2) nanowire have been analyzed using electron holography.
      The charges and electric fields in electrophotographic materials such as toner
      particles and organic photoconductors have been quantitatively evaluated after
      equipping the specimen holder with a piezodriving probe to shield the specimens
      from electron irradiation. The conductivity and electric field variations in the
      case of Ag-based conductive adhesives have been analyzed by applying an electric
      current through the holder. Finally, the characteristic charging effect induced
      by electron irradiation in biological specimens has been studied. It has also
      been pointed out that under certain experimental conditions, the stationary
      orbits of electron-induced secondary electrons can be located by electric field
      visualization.

PMID- 21844593
TI  - Electron microscopy at a sub-50 pm resolution.
AB  - An aberration-corrected electron microscope developed in CREST project has been
      applied for imaging atoms and clusters buried inside crystals. The resolution of
      the microscope in scanning transmission electron microscopy (STEM) has
      experimentally proved to be better than 47 pm by use of a cold-field emission gun
      at 300 kV. The high resolution has given an advantage for imaging light elements
      such as lithium atoms discriminating one by one. Moreover, a three-dimensional
      structure imaging has been demonstrated for dopant clusters by a sub-50 pm STEM,
      using its high depth resolution.

PMID- 21844594
TI  - Convergent-beam electron diffraction.
AB  - This paper reviews the convergent-beam electron diffraction (CBED) technique.
      Point- and space-group determination methods of ordinary crystals are described,
      along with an example of the determination method for Sr3Ru2O7. The symmetry
      determination of one-dimensionally incommensurate crystals and quasicrystals is
      explained. The large-angle CBED technique, which is indispensable for lattice
      defect and lattice strain analysis, is also described. A real procedure for
      lattice strain analysis is provided, using an example of a multilayer Si1
      xGe(x)/Si material. A nanometer-scale crystal structure refinement method and
      charge density and crystal potential determination method by CBED are briefly
      described.

PMID- 21844595
TI  - Picoscale science and nanoscale engineering by electron microscopy.
AB  - A future scanning/transmission electron microscope is proposed to be a
      comprehensive machine that is capable of providing picoseconds time-resolved
      information at sub-nanometer scale and even at picometer scale, spatial
      resolution. At the same time, physical and chemical properties can be measured in
      situ from a region as small as a few nanometers by introducing local electric,
      mechanical, thermal, magnetic and/or optical stimulations/excitations under
      vacuum or even in a quasi-ambient environment. It is anticipated that nanoscopy
      and picoscopy will be key tools for studying picoscale science and developing
      nanoscale technology related to materials science, biology, physics and
      chemistry.

PMID- 21844596
TI  - In commemoration of Journal of Electron Microscopy's 60th anniversary.

PMID- 21844597
TI  - In celebration of the 60th anniversary of Journal of Electron Microscopy.

PMID- 21844599
TI  - Dynamics of the mammalian sperm membrane modification leading to fertilization: a
      cytological study.
AB  - Fertilization occurs when the sperm penetrates the egg, resulting in the
      combination of paternal and maternal genomes for the propagation of generations.
      To perform the task, the mammalian sperm membrane system, constructed during
      spermatogenesis, undergoes biochemical and cytological modifications. In this
      review, the following three points are discussed: (i) the nature of the acrosomal
      membrane disclosed by various types of microscopy, including transmission
      electron microscopy and the recently developed high-resolution fluorescence
      microscopy, (ii) the nascent acrosomal membrane dysfunction during acrosome
      biogenesis and (iii) the modification of the sperm membrane during sperm-egg
      interaction.

PMID- 21844600
TI  - Another 60 years in electron microscopy: development of phase-plate electron
      microscopy and biological applications.
AB  - It has been six decades since the concept of phase-plate electron microscopy was
      first reported by Boersch, but an experimental report on a phase plate with a
      theoretically rational performance has only recently been released by a group
      including the present author. Currently, many laboratories around the world are
      attempting to develop a wide range of phase plates to enhance the capabilities of
      transmission electron microscopy. They are reporting not only advantages of their
      own developments but also a fundamental problem inherent to electron beam
      devices, namely charging, i.e. the accumulation of electrostatic charge. In this
      report, we review the 60-year history of phase-plate development, with a
      particular focus on the fundamental issue of phase-plate charging. Next, we
      review biological applications of qualified phase plates, which have been
      successful in avoiding charging to some extent. Finally, we compare and discuss
      electron microscopic images, taken with or without phase plates, of biological
      targets such as proteins (GroEL and TRPV4), protein complexes (flagellar motor),
      viruses (T4 phage, epsilon-15 phage and herpes simplex virus), bacterial
      (cyanobacteria) and mammalian (PtK2) cells.

PMID- 21844598
TI  - The origins and evolution of freeze-etch electron microscopy.
AB  - The introduction of the Balzers freeze-fracture machine by Moor in 1961 had a
      much greater impact on the advancement of electron microscopy than he could have
      imagined. Devised originally to circumvent the dangers of classical thin-section
      techniques, as well as to provide unique en face views of cell membranes, freeze
      fracturing proved to be crucial for developing modern concepts of how biological
      membranes are organized and proved that membranes are bilayers of lipids within
      which proteins float and self-assemble. Later, when freeze-fracturing was
      combined with methods for freezing cells that avoided the fixation and
      cryoprotection steps that Moor still had to use to prepare the samples for his
      original invention, it became a means for capturing membrane dynamics on the
      millisecond time-scale, thus allowing a deeper understanding of the functions of
      biological membranes in living cells as well as their static ultrastructure.
      Finally, the realization that unfixed, non-cryoprotected samples could be deeply
      vacuum-etched or even freeze-dried after freeze-fracturing opened up a whole new
      way to image all the other molecular components of cells besides their membranes
      and also provided a powerful means to image the interactions of all the
      cytoplasmic components with the various membranes of the cell. The purpose of
      this review is to outline the history of these technical developments, to
      describe how they are being used in electron microscopy today and to suggest how
      they can be improved in order to further their utility for biological electron
      microscopy in the future.

PMID- 21844601
TI  - From electron microscopy to molecular cell biology, molecular genetics and
      structural biology: intracellular transport and kinesin superfamily proteins,
      KIFs: genes, structure, dynamics and functions.
AB  - Cells transport and sort various proteins and lipids following synthesis as
      distinct types of membranous organelles and protein complexes to the correct
      destination at appropriate velocities. This intracellular transport is
      fundamental for cell morphogenesis, survival and functioning not only in highly
      polarized neurons but also in all types of cells in general. By developing quick
      freeze electron microscopy (EM), new filamentous structures associated with
      cytoskeletons are uncovered. The characterization of chemical structures and
      functions of these new filamentous structures led us to discover kinesin
      superfamily molecular motors, KIFs. In this review, I discuss the identification
      of these new structures and characterization of their functions using molecular
      cell biology and molecular genetics. KIFs not only play significant roles by
      transporting various cargoes along microtubule rails, but also play unexpected
      fundamental roles on various important physiological processes such as learning
      and memory, brain wiring, development of central nervous system and peripheral
      nervous system, activity-dependent neuronal survival, development of early
      embryo, left-right determination of our body and tumourigenesis. Furthermore, by
      combining single-molecule biophysics with structural biology such as cryo
      electrom microscopy and X-ray crystallography, atomic structures of KIF1A motor
      protein of almost all states during ATP hydrolysis have been determined and a
      common mechanism of motility has been proposed. Thus, this type of studies could
      be a good example of really integrative multidisciplinary life science in the
      twenty-first century.

PMID- 21844602
TI  - Perspectives on electron cryo-tomography of vitreous cryo-sections.
AB  - A major objective of modern structural biology is to appreciate the cellular
      organization by elucidating the spatial arrangement of macromolecular complexes
      within a cell. Cryogenic sample preparation, combined with cryo-ultramicrotomy,
      enables large cells and pieces of biological tissues to be thinned for electron
      cryo-tomography, which provides a three-dimensional view of the biological
      sample. There are, however, limitations associated with the technique that must
      be realized, addressed and overcome for the procedure to become mainstream. Here,
      we provide perspectives on the continued advancements in cryogenic sample
      preparation for vitreous cryo-sectioning, image collection and post-image
      processing that have expanded the attainable information limit within the three
      dimensional reconstructions of cells and pieces of biological tissues.

PMID- 21844605
TI  - Effect of object width on muscle and joint forces during thumb-index finger
      grasping.
AB  - The objective of this study was to identify the impact of modifying the object
      width on muscle and joint forces while gripping objects. The experimental
      protocol consisted to maintain horizontally five objects of different widths
      (3.5, 4.5, 5.5, 6.5, and 7.5 cm) with a thumb-index finger grip. Subjects were
      required to grasp spontaneously the object without any instruction regarding the
      grip force (GF) to apply. A biomechanical model of thumb-index finger pinch was
      developed to estimate muscle and joint forces. This model included
      electromyography, fingertip force, and kinematics data as inputs. The finger
      joint postures and the GF varied across the object widths. The estimated muscle
      forces also varied significantly according to the object width. Interestingly, we
      observed that the muscle force/GF ratios of major flexor muscles remain
      particularly stable with respect to the width whereas other muscle ratios
      differed largely. This may argue for a control strategy in which the actions of
      flexors were preserved in spite of change in joint postures. The estimated joint
      forces tended to increase with object width and increased in the distal-proximal
      sense. Overall, these results are of importance for the ergonomic design of
      handheld objects and for clinical applications.

PMID- 21844606
TI  - Altered alignment of the shoulder girdle and cervical spine in patients with
      insidious onset neck pain and whiplash-associated disorder.
AB  - Clinical theory suggests that altered alignment of the shoulder girdle has the
      potential to create or sustain symptomatic mechanical dysfunction in the cervical
      and thoracic spine. The alignment of the shoulder girdle is described by two
      clavicle rotations, i.e, elevation and retraction, and by three scapular
      rotations, i.e., upward rotation, internal rotation, and anterior tilt. Elevation
      and retraction have until now been assessed only in patients with neck pain. The
      aim of the study was to determine whether there is a pattern of altered alignment
      of the shoulder girdle and the cervical and thoracic spine in patients with neck
      pain. A three-dimensional device measured clavicle and scapular orientation, and
      cervical and thoracic alignment in patients with insidious onset neck pain (IONP)
      and whiplash-associated disorder (WAD). An asymptomatic control group was
      selected for baseline measurements. The symptomatic groups revealed a
      significantly reduced clavicle retraction and scapular upward rotation as well as
      decreased cranial angle. A difference was found between the symptomatic groups on
      the left side, whereas the WAD group revealed an increased scapular anterior tilt
      and the IONP group a decreased clavicle elevation. These changes may be an
      important mechanism for maintenance and recurrence or exacerbation of symptoms in
      patients with neck pain.

PMID- 21844604
TI  - Associations between pre-pregnancy obesity and asthma symptoms in adolescents.
AB  - BACKGROUND: The high prevalence of children's asthma symptoms, worldwide, is
      unexplained. We examined the relation between maternal pre-pregnancy weight and
      body mass index (BMI), and asthma symptoms in adolescents. METHODS: Data from
      6945 adolescents born within the Northern Finland Birth Cohort 1986 were used.
      Prospective antenatal and birth outcome data, including maternal pre-pregnancy
      weight and BMI, and asthma symptoms in adolescent offspring at age 15-16 years,
      were employed. Logistic regression analyses were performed to examine the
      associations between relevant prenatal factors and asthma symptoms during
      adolescence. RESULTS: Current wheeze (within the past year) was reported by 10.6%
      of adolescents, and physician-diagnosed asthma by 6.0%. High maternal pre
      pregnancy BMI was a significant predictor of wheeze in the adolescents (increase
      per kilogram per square metre unit; 2.7%, 95% CI 0.9 to 4.4 for ever wheeze;
      3.5%, 95% CI 1.3 to 5.8 for current wheeze), and adjusting for potential
      confounders further increased the risk (2.8%, 95% CI 0.5 to 5.1; 4.7%, 95% CI 1.9
      to 7.7, respectively). High maternal pre-pregnancy weight, in the top tertile,
      also significantly increased the odds of current wheeze in the adolescent by 20%
      (95% CI 4 to 39), and adjusting for potential confounders further increased the
      risk (OR=1.52, 95% CI 1.19 to 1.95). Results were similar for current asthma.
      Furthermore, these significant associations were observed only among adolescents
      without parental history of atopy but not among those with parental history of
      atopy. CONCLUSIONS: The association demonstrated here between maternal pre
      pregnancy overweight and obesity, and asthma symptoms in adolescents suggests
      that increase in asthma may be partly related to the rapid rise in obesity in
      recent years.

PMID- 21844607
TI  - Shoulder muscular activity during isometric three-point kneeling exercise on
      stable and unstable surfaces.
AB  - The purpose of this study was to determine if performing isometric 3-point
      kneeling exercises on a Swiss ball influenced the isometric force output and EMG
      activities of the shoulder muscles when compared with performing the same
      exercises on a stable base of support. Twenty healthy adults performed the
      isometric 3-point kneeling exercises with the hand placed either on a stable
      surface or on a Swiss ball. Surface EMG was recorded from the posterior deltoid,
      pectoralis major, biceps brachii, triceps brachii, upper trapezius, and serratus
      anterior muscles using surface differential electrodes. All EMG data were
      reported as percentages of the average root mean square (RMS) values obtained in
      maximum voluntary contractions for each muscle studied. The highest load value
      was obtained during exercise on a stable surface. A significant increase was
      observed in the activation of glenohumeral muscles during exercises on a Swiss
      ball. However, there were no differences in EMG activities of the scapulothoracic
      muscles. These results suggest that exercises performed on unstable surfaces may
      provide muscular activity levels similar to those performed on stable surfaces,
      without the need to apply greater external loads to the musculoskeletal system.
      Therefore, exercises on unstable surfaces may be useful during the process of
      tissue regeneration.

PMID- 21844608
TI  - Differences in geriatric anthropometric data between DXA-based subject-specific
      estimates and non-age-specific traditional regression models.
AB  - Age, obesity, and gender can have a significant impact on the anthropometrics of
      adults aged 65 and older. The aim of this study was to investigate differences in
      body segment parameters derived using two methods: (1) a dual-energy x-ray
      absorptiometry (DXA) subject-specific method (Chambers et al., 2010) and (2)
      traditional regression models (de Leva, 1996). The impact of aging, gender, and
      obesity on the potential differences between these methods was examined. Eighty
      three healthy older adults were recruited for participation. Participants
      underwent a whole-body DXA scan (Hologic QDR 1000/W). Mass, length, center of
      mass, and radius of gyration were determined for each segment. In addition,
      traditional regressions were used to estimate these parameters (de Leva, 1996). A
      mixed linear regression model was performed (alpha = 0.05). Method type was
      significant in every variable of interest except forearm segment mass. The
      obesity and gender differences that we observed translate into differences
      associated with using traditional regressions to predict anthropometric variables
      in an aging population. Our data point to a need to consider age, obesity, and
      gender when utilizing anthropometric data sets and to develop regression models
      that accurately predict body segment parameters in the geriatric population,
      considering gender and obesity.

PMID- 21844609
TI  - Relative net vertical impulse determines jumping performance.
AB  - The purpose of this investigation was to determine the relationship between
      relative net vertical impulse and jump height in a countermovement jump and
      static jump performed to varying squat depths. Ten college-aged males with 2
      years of jumping experience participated in this investigation (age: 23.3 +/- 1.5
      years; height: 176.7 +/- 4.5 cm; body mass: 84.4 +/- 10.1 kg). Subjects performed
      a series of static jumps and countermovement jumps in a randomized fashion to a
      depth of 0.15, 0.30, 0.45, 0.60, and 0.75 m and a self-selected depth (static
      jump depth = 0.38 +/- 0.08 m, countermovement jump depth = 0.49 +/- 0.06 m).
      During the concentric phase of each jump, peak force, peak velocity, peak power,
      jump height, and net vertical impulse were recorded and analyzed. Net vertical
      impulse was divided by body mass to produce relative net vertical impulse.
      Increasing squat depth corresponded to a decrease in peak force and an increase
      in jump height and relative net vertical impulse for both static jump and
      countermovement jump. Across all depths, relative net vertical impulse was
      statistically significantly correlated to jump height in the static jump (r =
      .9337, p < .0001, power = 1.000) and countermovement jump (r = .925, p < .0001,
      power = 1.000). Across all depths, peak force was negatively correlated to jump
      height in the static jump (r = -0.3947, p = .0018, power = 0.8831) and
      countermovement jump (r = -0.4080, p = .0012, power = 0.9050). These results
      indicate that relative net vertical impulse can be used to assess vertical jump
      performance, regardless of initial squat depth, and that peak force may not be
      the best measure to assess vertical jump performance.

PMID- 21844612
TI  - Forces and moments on the knee during kneeling and squatting.
AB  - Euler angle decomposition and inverse dynamics were used to determine the knee
      angles and net forces and moments applied to the tibia during kneeling and
      squatting with and without kneepads for 10 subjects in four postures: squatting
      (Squat), kneeling on the right knee (One Knee), bilateral kneeling near full
      flexion (Near Full) and bilateral kneeling near 90 degrees  flexion (Near 90).
      Kneepads affected the knee flexion (p = .002), medial forces (p = .035), and
      internal rotation moments (p = .006). Squat created loading conditions that had
      higher varus (p < .001) and resultant moments (p = .027) than kneeling. One Knee
      resulted in the highest force magnitudes and net moments (p < .001) of the
      kneeling postures. Thigh-calf and heel-gluteus contact forces decreased the
      flexion moment on average by 48% during Squat and Near Full.

PMID- 21844611
TI  - Relationship between eccentric hip torque and lower-limb kinematics: gender
      differences.
AB  - The purposes of this study were to compare lower-limb kinematics between genders,
      and determine the relationships among eccentric hip abductor and lateral rotator
      torques and lower-limb kinematics. The movements of the pelvis, femur, and knee
      were calculated for 16 women and 16 men during the single-leg squat. Eccentric
      hip abductor and lateral rotator torques were measured using an isokinetic
      dynamometer. The results showed that women had greater contralateral pelvic
      depression, femur adduction, and knee abduction than men. The eccentric hip
      abductor and lateral rotator torques were correlated with coronal plane femur and
      knee movements in the overall sample. When the genders were analyzed separately,
      it was observed that women with greater eccentric hip abductor torque exhibited
      less femur adduction and femur medial rotation, and greater knee adduction
      excursion. No significant relationship was observed between the isokinetic and
      kinematic variables in the male group. The differences between the genders help
      to explain the greater rate of knee disorders observed in women. Moreover, the
      eccentric hip abduction action seemed to be more important in women to control
      the lower-limb movements.

PMID- 21844613
TI  - Rotational biomechanics of the elite golf swing: benchmarks for amateurs.
AB  - The purpose of this study was to determine biomechanical factors that may
      influence golf swing power generation. Three-dimensional kinematics and kinetics
      were examined in 10 professional and 5 amateur male golfers. Upper-torso
      rotation, pelvic rotation, X-factor (relative hip-shoulder rotation), O-factor
      (pelvic obliquity), S-factor (shoulder obliquity), and normalized free moment
      were assessed in relation to clubhead speed at impact (CSI). Among professional
      golfers, results revealed that peak free moment per kilogram, peak X-factor, and
      peak S-factor were highly consistent, with coefficients of variation of 6.8%,
      7.4%, and 8.4%, respectively. Downswing was initiated by reversal of pelvic
      rotation, followed by reversal of upper-torso rotation. Peak X-factor preceded
      peak free moment in all swings for all golfers, and occurred during initial
      downswing. Peak free moment per kilogram, X-factor at impact, peak X-factor, and
      peak upper-torso rotation were highly correlated to CSI (median correlation
      coefficients of 0.943, 0.943, 0.900, and 0.900, respectively). Benchmark curves
      revealed kinematic and kinetic temporal and spatial differences of amateurs
      compared with professional golfers. For amateurs, the number of factors that fell
      outside 1-2 standard deviations of professional means increased with handicap.
      This study identified biomechanical factors highly correlated to golf swing power
      generation and may provide a basis for strategic training and injury prevention.

PMID- 21844614
TI  - A comparison of kinematics between overarm throwing with 20% underweight,
      regular, and 20% overweight balls.
AB  - The aim of this study was to compare the kinematics in throwing with a regular
      weighted handball with 20% lighter and heavier balls in female experienced
      handball players. In total, eight joint movements during the throw were analyzed.
      The analysis consisted of maximal angles, angles at ball release, and maximal
      angular velocities of the joint movements and their timings during the throw.
      Results on 24 experienced female team handball players (mean age 18.2 +/- 2.1
      years) showed that the difference in ball weight affected the maximal ball
      velocity. The difference in ball release velocity was probably a result of the
      significant differences in kinematics of the major contributors to overarm
      throwing: elbow extension and internal rotation of the shoulder. These were
      altered when changing the ball weight, which resulted in differences in ball
      release velocity.

PMID- 21844610
TI  - Preferential quadriceps activation in female athletes with incremental increases
      in landing intensity.
AB  - The purpose of this study was to identify alterations in preparatory muscle
      activation patterns across different drop heights in female athletes. Sixteen
      female high school volleyball players performed the drop vertical jump from three
      different drop heights. Surface electromyography of the quadriceps and hamstrings
      were collected during the movement trials. As the drop height increased, muscle
      activation of the quadriceps during preparatory phase also increased (p < .05).
      However, the hamstrings activation showed no similar increases relative to drop
      height. Female athletes appear to preferentially rely on increased quadriceps
      activation, without an increase in hamstrings activation, with increased
      plyometric intensity. The resultant decreased activation ratio of the hamstrings
      relative to quadriceps before landing may represent altered dynamic knee
      stability and may contribute to the increased risk of ACL injury in female
      athletes.

PMID- 21844615
TI  - Can the effect of soft tissue artifact be eliminated in upper-arm internal
      external rotation?
AB  - The purpose of this study was to quantify the effect of soft tissue artifact
      during three-dimensional motion capture and assess the effectiveness of an
      optimization method to reduce this effect. Four subjects were captured performing
      upper-arm internal-external rotation with retro-reflective marker sets attached
      to their upper extremities. A mechanical arm, with the same marker set attached,
      replicated the tasks human subjects performed. Artificial sinusoidal noise was
      then added to the recorded mechanical arm data to simulate soft tissue artifact.
      All data were processed by an optimization model. The result from both human and
      mechanical arm kinematic data demonstrates that soft tissue artifact can be
      reduced by an optimization model, although this error cannot be successfully
      eliminated. The soft tissue artifact from human subjects and the simulated soft
      tissue artifact from artificial sinusoidal noise were demonstrated to be
      considerably different. It was therefore concluded that the kinematic noise
      caused by skin movement artifact during upper-arm internal-external rotation does
      not follow a sinusoidal pattern and cannot be effectively eliminated by an
      optimization model.

PMID- 21844616
TI  - Commercial video frame rates can produce reliable results for both normal and CP
      spastic gait's spatiotemporal, angular, and linear displacement variables.
AB  - To investigate what sampling frequency is adequate for gait, the correlation of
      spatiotemporal parameters and the kinematic differences, between normal and CP
      spastic gait, for three sampling frequencies (100 Hz, 50 Hz, 25 Hz) were
      assessed. Spatiotemporal, angular, and linear displacement variables in the
      sagittal plane along with their 1st and 2nd derivatives were analyzed.
      Spatiotemporal stride parameters were highly correlated among the three sampling
      frequencies. The statistical model (2 * 3 ANOVA) gave no interactions between the
      factors group and frequency, indicating that group differences were invariant of
      sampling frequency. Lower frequencies led to smoother curves for all the
      variables, with a loss of information though, especially for the 2nd derivatives,
      having a homologous effect as the one of oversmoothing. It is proposed that in
      the circumstance that only spatiotemporal stride parameters, as well as angular
      and linear displacements are to be used, in gait reports, then commercial video
      camera speeds (25/30 Hz, 50/60 Hz when deinterlaced) can be considered as a low
      cost solution to produce acceptable results.

PMID- 21844617
TI  - Direct kinematic modeling of the upper limb during trunk-assisted reaching.
AB  - The study proposes a rigid-body biomechanical model of the trunk and whole upper
      limb including scapula and the test of this model with a kinematic method using a
      six-dimensional (6-D) electromagnetic motion capture (mocap) device. Large
      unconstrained natural trunk-assisted reaching movements were recorded in 7
      healthy subjects. The 3-D positions of anatomical landmarks were measured and
      then compared to their estimation given by the biomechanical chain fed with joint
      angles (the direct kinematics). Thus, the prediction errors was attributed to the
      different joints and to the different simplifications introduced in the model.
      Large (approx. 4 cm) end-point prediction errors at the level of the hand were
      reduced (to approx. 2 cm) if translations of the scapula were taken into account.
      As a whole, the 6-D mocap seems to give accurate results, except for prono
      supination. The direct kinematic model could be used as a virtual mannequin for
      other applications, such as computer animation or clinical and ergonomical
      evaluations.

PMID- 21844618
TI  - Tracking pedestrians using local spatio-temporal motion patterns in extremely
      crowded scenes.
AB  - Tracking pedestrians is a vital component of many computer vision applications,
      including surveillance, scene understanding, and behavior analysis. Videos of
      crowded scenes present significant challenges to tracking due to the large number
      of pedestrians and the frequent partial occlusions that they produce. The
      movement of each pedestrian, however, contributes to the overall crowd motion
      (i.e., the collective motions of the scene's constituents over the entire video)
      that exhibits an underlying spatially and temporally varying structured pattern.
      In this paper, we present a novel Bayesian framework for tracking pedestrians in
      videos of crowded scenes using a space-time model of the crowd motion. We
      represent the crowd motion with a collection of hidden Markov models trained on
      local spatio-temporal motion patterns, i.e., the motion patterns exhibited by
      pedestrians as they move through local space-time regions of the video. Using
      this unique representation, we predict the next local spatio-temporal motion
      pattern a tracked pedestrian will exhibit based on the observed frames of the
      video. We then use this prediction as a prior for tracking the movement of an
      individual in videos of extremely crowded scenes. We show that our approach of
      leveraging the crowd motion enables tracking in videos of complex scenes that
      present unique difficulty to other approaches.

PMID- 21844619
TI  - Quantifying and transferring contextual information in object detection.
AB  - Context is critical for reducing the uncertainty in object detection. However,
      context modeling is challenging because there are often many different types of
      contextual information coexisting with different degrees of relevance to the
      detection of target object(s) in different images. It is therefore crucial to
      devise a context model to automatically quantify and select the most effective
      contextual information for assisting in detecting the target object.
      Nevertheless, the diversity of contextual information means that learning a
      robust context model requires a larger training set than learning the target
      object appearance model, which may not be available in practice. In this work, a
      novel context modeling framework is proposed without the need for any prior scene
      segmentation or context annotation. We formulate a polar geometric context
      descriptor for representing multiple types of contextual information. In order to
      quantify context, we propose a new maximum margin context (MMC) model to evaluate
      and measure the usefulness of contextual information directly and explicitly
      through a discriminant context inference method. Furthermore, to address the
      problem of context learning with limited data, we exploit the idea of transfer
      learning based on the observation that although two categories of objects can
      have very different visual appearance, there can be similarity in their context
      and/or the way contextual information helps to distinguish target objects from
      nontarget objects. To that end, two novel context transfer learning models are
      proposed which utilize training samples from source object classes to improve the
      learning of the context model for a target object class based on a joint maximum
      margin learning framework. Experiments are carried out on PASCAL VOC2005 and
      VOC2007 data sets, a luggage detection data set extracted from the i-LIDS data
      set, and a vehicle detection data set extracted from outdoor surveillance
      footage. Our results validate the effectiveness of the proposed models for
      quantifying and transferring contextual information, and demonstrate that they
      outperform related alternative context models.

PMID- 21844621
TI  - Mean shift trackers with cross-bin metrics.
AB  - Cross-bin metrics have been shown to be more suitable than bin-by-bin metrics for
      measuring the distance between histograms in various applications. In particular,
      a visual tracker that minimizes the earth mover's distance (EMD) between the
      candidate and reference feature histograms has recently been proposed. This
      tracker was shown to be more robust than the Mean Shift tracker, which employs a
      bin-by-bin metric. In each frame, the former tracker iteratively shifts the
      candidate location by one pixel in the direction opposite to the EMD's gradient
      until no improvement is made. This optimization process involves the clustering
      of the candidate feature density in feature space, as well as the computation of
      the EMD between the candidate and reference feature histograms after each shift
      of the candidate location. In this paper, alternative trackers that employ cross
      bin metrics as well, but that are based on Mean Shift (MS) iterations, are
      derived. The proposed trackers are simpler and faster due to 1) the use of MS
      based optimization, which is not restricted to single pixel shifts, 2) abstention
      from any clustering of feature densities, and 3) abstention from EMD computations
      in multidimensional spaces.

PMID- 21844622
TI  - Vision-based analysis of small groups in pedestrian crowds.
AB  - Building upon state-of-the-art algorithms for pedestrian detection and multi
      object tracking, and inspired by sociological models of human collective
      behavior, we automatically detect small groups of individuals who are traveling
      together. These groups are discovered by bottom-up hierarchical clustering using
      a generalized, symmetric Hausdorff distance defined with respect to pairwise
      proximity and velocity. We validate our results quantitatively and qualitatively
      on videos of real-world pedestrian scenes. Where human-coded ground truth is
      available, we find substantial statistical agreement between our results and the
      human-perceived small group structure of the crowd. Results from our automated
      crowd analysis also reveal interesting patterns governing the shape of pedestrian
      groups. These discoveries complement current research in crowd dynamics, and may
      provide insights to improve evacuation planning and real-time situation awareness
      during public disturbances.

PMID- 21844623
TI  - Tracking mobile users in wireless networks via semi-supervised colocalization.
AB  - Recent years have witnessed the growing popularity of sensor and sensor-network
      technologies, supporting important practical applications. One of the fundamental
      issues is how to accurately locate a user with few labeled data in a wireless
      sensor network, where a major difficulty arises from the need to label large
      quantities of user location data, which in turn requires knowledge about the
      locations of signal transmitters or access points. To solve this problem, we have
      developed a novel machine learning-based approach that combines collaborative
      filtering with graph-based semi-supervised learning to learn both mobile users'
      locations and the locations of access points. Our framework exploits both labeled
      and unlabeled data from mobile devices and access points. In our two-phase
      solution, we first build a manifold-based model from a batch of labeled and
      unlabeled data in an offline training phase and then use a weighted k-nearest
      neighbor method to localize a mobile client in an online localization phase. We
      extend the two-phase colocalization to an online and incremental model that can
      deal with labeled and unlabeled data that come sequentially and adapt to
      environmental changes. Finally, we embed an action model to the framework such
      that additional kinds of sensor signals can be utilized to further boost the
      performance of mobile tracking. Compared to other state-of-the-art systems, our
      framework has been shown to be more accurate while requiring less calibration
      effort in our experiments performed on three different testbeds.

PMID- 21844624
TI  - A multimedia retrieval framework based on semi-supervised ranking and relevance
      feedback.
AB  - We present a new framework for multimedia content analysis and retrieval which
      consists of two independent algorithms. First, we propose a new semi-supervised
      algorithm called ranking with Local Regression and Global Alignment (LRGA) to
      learn a robust Laplacian matrix for data ranking. In LRGA, for each data point, a
      local linear regression model is used to predict the ranking scores of its
      neighboring points. A unified objective function is then proposed to globally
      align the local models from all the data points so that an optimal ranking score
      can be assigned to each data point. Second, we propose a semi-supervised long
      term Relevance Feedback (RF) algorithm to refine the multimedia data
      representation. The proposed long-term RF algorithm utilizes both the multimedia
      data distribution in multimedia feature space and the history RF information
      provided by users. A trace ratio optimization problem is then formulated and
      solved by an efficient algorithm. The algorithms have been applied to several
      content-based multimedia retrieval applications, including cross-media retrieval,
      image retrieval, and 3D motion/pose data retrieval. Comprehensive experiments on
      four data sets have demonstrated its advantages in precision, robustness,
      scalability, and computational efficiency.

PMID- 21844625
TI  - Holistic context models for visual recognition.
AB  - A novel framework to context modeling based on the probability of co-occurrence
      of objects and scenes is proposed. The modeling is quite simple, and builds upon
      the availability of robust appearance classifiers. Images are represented by
      their posterior probabilities with respect to a set of contextual models, built
      upon the bag-of-features image representation, through two layers of
      probabilistic modeling. The first layer represents the image in a semantic space,
      where each dimension encodes an appearance-based posterior probability with
      respect to a concept. Due to the inherent ambiguity of classifying image patches,
      this representation suffers from a certain amount of contextual noise. The second
      layer enables robust inference in the presence of this noise by modeling the
      distribution of each concept in the semantic space. A thorough and systematic
      experimental evaluation of the proposed context modeling is presented. It is
      shown that it captures the contextual "gist" of natural images. Scene
      classification experiments show that contextual classifiers outperform their
      appearance-based counterparts, irrespective of the precise choice and accuracy of
      the latter. The effectiveness of the proposed approach to context modeling is
      further demonstrated through a comparison to existing approaches on scene
      classification and image retrieval, on benchmark data sets. In all cases, the
      proposed approach achieves superior results.

PMID- 21844626
TI  - Partially supervised speaker clustering.
AB  - Content-based multimedia indexing, retrieval, and processing as well as
      multimedia databases demand the structuring of the media content (image, audio,
      video, text, etc.), one significant goal being to associate the identity of the
      content to the individual segments of the signals. In this paper, we specifically
      address the problem of speaker clustering, the task of assigning every speech
      utterance in an audio stream to its speaker. We offer a complete treatment to the
      idea of partially supervised speaker clustering, which refers to the use of our
      prior knowledge of speakers in general to assist the unsupervised speaker
      clustering process. By means of an independent training data set, we encode the
      prior knowledge at the various stages of the speaker clustering pipeline via 1)
      learning a speaker-discriminative acoustic feature transformation, 2) learning a
      universal speaker prior model, and 3) learning a discriminative speaker subspace,
      or equivalently, a speaker-discriminative distance metric. We study the
      directional scattering property of the Gaussian mixture model (GMM) mean
      supervector representation of utterances in the high-dimensional space, and
      advocate exploiting this property by using the cosine distance metric instead of
      the euclidean distance metric for speaker clustering in the GMM mean supervector
      space. We propose to perform discriminant analysis based on the cosine distance
      metric, which leads to a novel distance metric learning algorithm-linear
      spherical discriminant analysis (LSDA). We show that the proposed LSDA
      formulation can be systematically solved within the elegant graph embedding
      general dimensionality reduction framework. Our speaker clustering experiments on
      the GALE database clearly indicate that 1) our speaker clustering methods based
      on the GMM mean supervector representation and vector-based distance metrics
      outperform traditional speaker clustering methods based on the "bag of acoustic
      features" representation and statistical model-based distance metrics, 2) our
      advocated use of the cosine distance metric yields consistent increases in the
      speaker clustering performance as compared to the commonly used euclidean
      distance metric, 3) our partially supervised speaker clustering concept and
      strategies significantly improve the speaker clustering performance over the
      baselines, and 4) our proposed LSDA algorithm further leads to state-of-the-art
      speaker clustering performance.

PMID- 21844627
TI  - Sparse Algorithms Are Not Stable: A No-Free-Lunch Theorem.
AB  - We consider two desired properties of learning algorithms: sparsity and
      algorithmic stability. Both properties are believed to lead to good
      generalization ability. We show that these two properties are fundamentally at
      odds with each other: A sparse algorithm cannot be stable and vice versa. Thus,
      one has to trade off sparsity and stability in designing a learning algorithm. In
      particular, our general result implies that l(1)-regularized regression (Lasso)
      cannot be stable, while l(2)-regularized regression is known to have strong
      stability properties and is therefore not sparse.

PMID- 21844628
TI  - Does the cost function matter in Bayes decision rule?
AB  - In many tasks in pattern recognition, such as automatic speech recognition (ASR),
      optical character recognition (OCR), part-of-speech (POS) tagging, and other
      string recognition tasks, we are faced with a well-known inconsistency: The Bayes
      decision rule is usually used to minimize string (symbol sequence) error,
      whereas, in practice, we want to minimize symbol (word, character, tag, etc.)
      error. When comparing different recognition systems, we do indeed use symbol
      error rate as an evaluation measure. The topic of this work is to analyze the
      relation between string (i.e., 0-1) and symbol error (i.e., metric, integer
      valued) cost functions in the Bayes decision rule, for which fundamental analytic
      results are derived. Simple conditions are derived for which the Bayes decision
      rule with integer-valued metric cost function and with 0-1 cost gives the same
      decisions or leads to classes with limited cost. The corresponding conditions can
      be tested with complexity linear in the number of classes. The results obtained
      do not make any assumption w.r.t. the structure of the underlying distributions
      or the classification problem. Nevertheless, the general analytic results are
      analyzed via simulations of string recognition problems with Levenshtein (edit)
      distance cost function. The results support earlier findings that considerable
      improvements are to be expected when initial error rates are high.

PMID- 21844629
TI  - The light field camera: extended depth of field, aliasing, and superresolution.
AB  - Portable light field (LF) cameras have demonstrated capabilities beyond
      conventional cameras. In a single snapshot, they enable digital image refocusing
      and 3D reconstruction. We show that they obtain a larger depth of field but
      maintain the ability to reconstruct detail at high resolution. In fact, all
      depths are approximately focused, except for a thin slab where blur size is
      bounded, i.e., their depth of field is essentially inverted compared to regular
      cameras. Crucial to their success is the way they sample the LF, trading off
      spatial versus angular resolution, and how aliasing affects the LF. We show that
      applying traditional multiview stereo methods to the extracted low-resolution
      views can result in reconstruction errors due to aliasing. We address these
      challenges using an explicit image formation model, and incorporate Lambertian
      and texture preserving priors to reconstruct both scene depth and its
      superresolved texture in a variational Bayesian framework, eliminating aliasing
      by fusing multiview information. We demonstrate the method on synthetic and real
      images captured with our LF camera, and show that it can outperform other
      computational camera systems.

PMID- 21844630
TI  - Accelerated hypothesis generation for multistructure data via preference
      analysis.
AB  - Random hypothesis generation is integral to many robust geometric model fitting
      techniques. Unfortunately, it is also computationally expensive, especially for
      higher order geometric models and heavily contaminated data. We propose a
      fundamentally new approach to accelerate hypothesis sampling by guiding it with
      information derived from residual sorting. We show that residual sorting innately
      encodes the probability of two points having arisen from the same model, and is
      obtained without recourse to domain knowledge (e.g., keypoint matching scores)
      typically used in previous sampling enhancement methods. More crucially, our
      approach encourages sampling within coherent structures and thus can very rapidly
      generate all-inlier minimal subsets that maximize the robust criterion. Sampling
      within coherent structures also affords a natural ability to handle
      multistructure data, a condition that is usually detrimental to other methods.
      The result is a sampling scheme that offers substantial speed-ups on common
      computer vision tasks such as homography and fundamental matrix estimation. We
      show on many computer vision data, especially those with multiple structures,
      that ours is the only method capable of retrieving satisfactory results within
      realistic time budgets.

PMID- 21844631
TI  - High accuracy and visibility-consistent dense multiview stereo.
AB  - Since the initial comparison of Seitz et al., the accuracy of dense multiview
      stereovision methods has been increasing steadily. A number of limitations,
      however, make most of these methods not suitable to outdoor scenes taken under
      uncontrolled imaging conditions. The present work consists of a complete dense
      multiview stereo pipeline which circumvents these limitations, being able to
      handle large-scale scenes without sacrificing accuracy. Highly detailed
      reconstructions are produced within very reasonable time thanks to two key stages
      in our pipeline: a minimum s-t cut optimization over an adaptive domain that
      robustly and efficiently filters a quasidense point cloud from outliers and
      reconstructs an initial surface by integrating visibility constraints, followed
      by a mesh-based variational refinement that captures small details, smartly
      handling photo-consistency, regularization, and adaptive resolution. The pipeline
      has been tested over a wide range of scenes: from classic compact objects taken
      in a laboratory setting, to outdoor architectural scenes, landscapes, and
      cultural heritage sites. The accuracy of its reconstructions has also been
      measured on the dense multiview benchmark proposed by Strecha et al., showing the
      results to compare more than favorably with the current state-of-the-art methods.

PMID- 21844632
TI  - Image restoration by matching gradient distributions.
AB  - The restoration of a blurry or noisy image is commonly performed with a MAP
      estimator, which maximizes a posterior probability to reconstruct a clean image
      from a degraded image. A MAP estimator, when used with a sparse gradient image
      prior, reconstructs piecewise smooth images and typically removes textures that
      are important for visual realism. We present an alternative deconvolution method
      called iterative distribution reweighting (IDR) which imposes a global constraint
      on gradients so that a reconstructed image should have a gradient distribution
      similar to a reference distribution. In natural images, a reference distribution
      not only varies from one image to another, but also within an image depending on
      texture. We estimate a reference distribution directly from an input image for
      each texture segment. Our algorithm is able to restore rich mid-frequency
      textures. A large-scale user study supports the conclusion that our algorithm
      improves the visual realism of reconstructed images compared to those of MAP
      estimators.

PMID- 21844633
TI  - Dot scissor: a single-click interface for mesh segmentation.
AB  - This paper presents a very easy-to-use interactive tool, which we call dot
      scissor, for mesh segmentation. The user's effort is reduced to placing only a
      single click where a cut is desired. Such a simple interface is made possible by
      a directional search strategy supported by a concavity-aware harmonic field and a
      robust voting scheme that selects the best isoline as the cut. With a concavity
      aware weighting scheme, the harmonic fields gather dense isolines along concave
      regions which are natural boundaries of semantic components. The voting scheme
      relies on an isoline-face scoring mechanism that considers both shape geometry
      and user intent. We show by extensive experiments and quantitative analysis that
      our tool advances the state-of-the-art segmentation methods in both simplicity of
      use and segmentation quality.

PMID- 21844634
TI  - Constructing and drawing regular planar split networks.
AB  - Split networks are commonly used to visualize collections of bipartitions, also
      called splits, of a finite set. Such collections arise, for example, in
      evolutionary studies. Split networks can be viewed as a generalization of
      phylogenetic trees and may be generated using the SplitsTree package. Recently,
      the NeighborNet method for generating split networks has become rather popular,
      in part because it is guaranteed to always generate a circular split system,
      which can always be displayed by a planar split network. Even so, labels must be
      placed on the "outside" of the network, which might be problematic in some
      applications. To help circumvent this problem, it can be helpful to consider so
      called flat split systems, which can be displayed by planar split networks where
      labels are allowed on the inside of the network too. Here, we present a new
      algorithm that is guaranteed to compute a minimal planar split network displaying
      a flat split system in polynomial time, provided the split system is given in a
      certain format. We will also briefly discuss two heuristics that could be useful
      for analyzing phylogeographic data and that allow the computation of flat split
      systems in this format in polynomial time.

PMID- 21844635
TI  - Output-sensitive algorithms for finding the nested common intervals of two
      general sequences.
AB  - The focus of this paper is the problem of finding all nested common intervals of
      two general sequences. Depending on the treatment one wants to apply to duplicate
      genes, Blin et al. introduced three models to define nested common intervals of
      two sequences: the uniqueness, the free-inclusion, and the bijection models. We
      consider all the three models. For the uniqueness and the bijection models, we
      give O(n + N(out))-time algorithms, where N(out) denotes the size of the output.
      For the free-inclusion model, we give an O(n(1+epsilon) + N(out))-time algorithm,
      where epsilon > 0 is an arbitrarily small constant. We also present an upper
      bound on the size of the output for each model. For the uniqueness and the free
      inclusion models, we show that N(out) = O(n2). Let C = Sigma(g?Gamma) o1(g)o2(g),
      where Gamma is the set of distinct genes, and o1(g) and o2(g) are, respectively,
      the numbers of copies of gene g in the two given sequences. For the bijection
      model, we show that N(out) = O(Cn). In this paper, we also study the problem of
      finding all approximate nested common intervals of two sequences on the bijection
      model. An O(deltan + N(out))-time algorithm is presented, where delta denotes the
      maximum number of allowed gaps. In addition, we show that for this problem N(out)
      is O(deltan3).

PMID- 21844636
TI  - The impact of normalization and phylogenetic information on estimating the
      distance for metagenomes.
AB  - Metagenomics enables the study of unculturable microorganisms in different
      environments directly. Discriminating between the compositional differences of
      metagenomes is an important and challenging problem. Several distance functions
      have been proposed to estimate the differences based on functional profiles or
      taxonomic distributions; however, the strengths and limitations of such functions
      are still unclear. Initially, we analyzed three well-known distance functions and
      found very little difference between them in the clustering of samples. This
      motivated us to incorporate suitable normalizations and phylogenetic information
      into the functions so that we could cluster samples from both real and synthetic
      data sets. The results indicate significant improvement in sample clustering over
      that derived by rank-based normalization with phylogenetic information,
      regardless of whether the samples are from real or synthetic microbiomes.
      Furthermore, our findings suggest that considering suitable normalizations and
      phylogenetic information is essential when designing distance functions for
      estimating the differences between metagenomes. We conclude that incorporating
      rank-based normalization with phylogenetic information into the distance
      functions helps achieve reliable clustering results.

PMID- 21844637
TI  - Exploiting the functional and taxonomic structure of genomic data by
      probabilistic topic modeling.
AB  - In this paper, we present a method that enable both homology-based approach and
      composition-based approach to further study the functional core (i.e., microbial
      core and gene core, correspondingly). In the proposed method, the identification
      of major functionality groups is achieved by generative topic modeling, which is
      able to extract useful information from unlabeled data. We first show that
      generative topic model can be used to model the taxon abundance information
      obtained by homology-based approach and study the microbial core. The model
      considers each sample as a "document," which has a mixture of functional groups,
      while each functional group (also known as a "latent topic") is a weight mixture
      of species. Therefore, estimating the generative topic model for taxon abundance
      data will uncover the distribution over latent functions (latent topic) in each
      sample. Second, we show that, generative topic model can also be used to study
      the genome-level composition of "N-mer" features (DNA subreads obtained by
      composition-based approaches). The model consider each genome as a mixture of
      latten genetic patterns (latent topics), while each functional pattern is a
      weighted mixture of the "N-mer" features, thus the existence of core genomes can
      be indicated by a set of common N-mer features. After studying the mutual
      information between latent topics and gene regions, we provide an explanation of
      the functional roles of uncovered latten genetic patterns. The experimental
      results demonstrate the effectiveness of proposed method.

PMID- 21844638
TI  - Structural SCOP superfamily level classification using unsupervised machine
      learning.
AB  - One of the major research directions in bioinformatics is that of assigning
      superfamily classification to a given set of proteins. The classification
      reflects the structural, evolutionary, and functional relatedness. These
      relationships are embodied in a hierarchical classification, such as the
      Structural Classification of Protein (SCOP), which is mostly manually curated.
      Such a classification is essential for the structural and functional analyses of
      proteins. Yet a large number of proteins remain unclassified. In this study, we
      have proposed an unsupervised machine learning approach to classify and assign a
      given set of proteins to SCOP superfamilies. In the method, we have constructed a
      database and similarity matrix using P-values obtained from an all-against-all
      BLAST run and trained the network with the ART2 unsupervised learning algorithm
      using the rows of the similarity matrix as input vectors, enabling the trained
      network to classify the proteins from 0.82 to 0.97 f-measure accuracy. The
      performance of ART2 has been compared with that of spectral clustering, Random
      forest, SVM, and HHpred. ART2 performs better than the others except HHpred.
      HHpred performs better than ART2 and the sum of errors is smaller than that of
      the other methods evaluated.

PMID- 21844639
TI  - A computational model for estimating recruitment of primary afferent fibers by
      intraneural stimulation in the dorsal root ganglia.
AB  - Primary afferent microstimulation has been proposed as a method for activating
      cutaneous and muscle afferent fibers to restore tactile and proprioceptive
      feedback after limb loss or peripheral neuropathy. Large populations of primary
      afferent fibers can be accessed directly by implanting microelectrode arrays in
      the dorsal root ganglia (DRG), which provide a compact and stable target for
      stimulating a diverse group of sensory fibers. To gain insight into factors
      affecting the number and types of primary afferents activated, we developed a
      computational model that simulates the recruitment of fibers in the feline L7
      DRG. The model comprises two parts. The first part is a single-fiber model used
      to describe the current-distance relation and was based on the McIntyre
      Richardson-Grill model for excitability. The second part uses the results of the
      singe-fiber model and published data on fiber size distributions to predict the
      probability of recruiting a given number of fibers as a function of stimulus
      intensity. The range of intensities over which exactly one fiber was recruited
      was approximately 0.5-5 uA (0.1-1 nC per phase); the stimulus intensity at which
      the probability of recruiting exactly one fiber was maximized was 2.3 uA.
      However, at 2.3 uA, it was also possible to recruit up to three fibers, albeit
      with a lower probability. Stimulation amplitudes up to 6 uA were tested with the
      population model, which showed that as the amplitude increased, the number of
      fibers recruited increased exponentially. The distribution of threshold
      amplitudes predicted by the model was similar to that previously reported by in
      vivo experimentation. Finally, the model suggested that medium diameter fibers
      (7.3-11.5 um) may be recruited with much greater probability than large diameter
      fibers (12.8-16 um). This model may be used to efficiently test a range of
      stimulation parameters and nerve morphologies to complement results from
      electrophysiology experiments and to aid in the design of microelectrode arrays
      for neural interfaces.

PMID- 21844640
TI  - Observation of interface carrier states in no-common-atom heterostructures
      ZnSe/BeTe.
AB  - The existence of intrinsic carrier interface states in heterostructures with no
      common atom at the interface (such as ZnSe/BeTe) is shown experimentally by
      ellipsometry and photoluminescence spectroscopy. These states are located on
      interfaces and lie inside the effective bandgap of the structure; they are
      characterized by a high density and a long lifetime. A tight binding model
      confirms theoretically the existence of these states in ZnSe/BeTe
      heterostructures for a ZnTe-type interface, in contrast to the case of the BeSe
      type interface for which they do not exist.

PMID- 21844641
TI  - Enhanced 3D fluorescence live cell imaging on nanoplasmonic substrate.
AB  - We have created a randomly distributed nanocone substrate on silicon coated with
      silver for surface-plasmon-enhanced fluorescence detection and 3D cell imaging.
      Optical characterization of the nanocone substrate showed it can support several
      plasmonic modes (in the 300-800 nm wavelength range) that can be coupled to a
      fluorophore on the surface of the substrate, which gives rise to the enhanced
      fluorescence. Spectral analysis suggests that a nanocone substrate can create
      more excitons and shorter lifetime in the model fluorophore Rhodamine 6G (R6G)
      due to plasmon resonance energy transfer from the nanocone substrate to the
      nearby fluorophore. We observed three-dimensional fluorescence enhancement on our
      substrate shown from the confocal fluorescence imaging of chinese hamster ovary
      (CHO) cells grown on the substrate. The fluorescence intensity from the
      fluorophores bound on the cell membrane was amplified more than 100-fold as
      compared to that on a glass substrate. We believe that strong scattering within
      the nanostructured area coupled with random scattering inside the cell resulted
      in the observed three-dimensional enhancement in fluorescence with higher
      photostability on the substrate surface.

PMID- 21844642
TI  - Preparation of graphene by jet cavitation.
AB  - Despite its bright prospects, graphene faces challenges including issues
      concerning mass production. Here we present a totally green approach whereby
      common crystal graphite can be exfoliated into graphene sheets in aqueous
      solution by jet cavitation. This is possible mainly because the tensile stress
      caused by graphite-solution interfacial reflection of compressive waves acts an
      intensive 'suction disk' on the graphite flakes. We confirm the presence of
      graphene sheets by diverse characterizations. The graphene yield by our method is
      estimated as ~ 4 wt%, which could potentially be improved by further processing.
      The method, of a mechanical nature, is powerful compared to the traditional low
      throughput micromechanical cleavage. Our work here illustrates jet cavitation as
      a facile, low cost, timesaving and laborsaving route, which can potentially be
      scaled up to mass production of graphene.

PMID- 21844643
TI  - In situ tensile testing of nanofibers by combining atomic force microscopy and
      scanning electron microscopy.
AB  - A nanomechanical testing set-up is developed by integrating an atomic force
      microscope (AFM) for force measurements with a scanning electron microscope (SEM)
      to provide imaging capabilities. Electrospun nanofibers of polyvinyl alcohol
      (PVA), nylon-6 and biological mineralized collagen fibrils (MCFs) from antler
      bone were manipulated and tensile-tested using the AFM-SEM set-up. The complete
      stress-strain behavior to failure of individual nanofibers was recorded and a
      diversity of mechanical properties observed, highlighting how this technique is
      able to elucidate mechanical behavior due to structural composition at nanometer
      length scales.

PMID- 21844644
TI  - Nanoshells for in vivo imaging using two-photon excitation microscopy.
AB  - Gold nanoshells have been intensively investigated and applied to various
      biomedical fields because of their flexible optical tunability and biological
      compatibility. They hold great potential to serve as luminescent contrast agents
      excitable with near-infrared (NIR) lasers. In this paper, we describe the
      development of nanoshells with a peak of plasmon resonance at 800 nm and their
      subsequent use for in vivo blood vessel imaging using two-photon excitation
      microscopy at an excitation wavelength of 750 nm. We were able to image single
      nanoshell particles in blood vessels and generate optical contrast for blood
      vessel structure using luminescent signals. These results confirm the feasibility
      of engineering nanoshells with controlled optical properties for single-particle
      based in vivo imaging.

PMID- 21844645
TI  - Connectedness percolation in monodisperse rod systems: clustering effects.
AB  - A model is presented that examines the impact of local clustering upon the
      percolation behaviour of interpenetrable rod-like particles. The percolation
      threshold, as well as percolation and backbone probabilities, are evaluated as
      functions of the particle aspect ratio and degree of clustering by way of an
      analogy to a lattice site percolation problem. The formation of local, physically
      connected cliques of particles is shown to raise the percolation threshold whilst
      reducing the percolation and backbone fractions for a fixed volume fraction of
      particles.

PMID- 21844646
TI  - Space of symmetry matrices with elements 0, +/-1 and complete geometric
      description; its properties and application.
AB  - A fixed set, that is the set of all lattice metrics corresponding to the
      arithmetic holohedry of a primitive lattice, is a natural tool for keeping track
      of the symmetry changes that may occur in a deformable lattice [Ericksen (1979).
      Arch. Rat. Mech. Anal. 72, 1-13; Michel (1995). Symmetry and Structural
      Properties of Condensed Matter, edited by T. Lulek, W. Florek & S. Walcerz.
      Singapore: Academic Press; Pitteri & Zanzotto (1996). Acta Cryst. A52, 830-838;
      and references quoted therein]. For practical applications it is desirable to
      limit the infinite number of arithmetic holohedries, and simplify their
      classification and construction of the fixed sets. A space of 480 matrices with
      cyclic consecutive powers, determinant 1, elements from {0, +/-1} and geometric
      description were analyzed and offered as the framework for dealing with the
      symmetry of reduced lattices. This matrix space covers all arithmetic holohedries
      of primitive lattice descriptions related to the three shortest lattice
      translations in direct or reciprocal spaces, and corresponds to the unique list
      of 39 fixed points with integer coordinates in six-dimensional space of lattice
      metrics. Matrices are presented by the introduced dual symbol, which sheds some
      light on the lattice and its symmetry-related properties, without further digging
      into matrices. By the orthogonal lattice distortion the lattice group-subgroup
      relations are easily predicted. It was proven and exemplified that new symbols
      enable classification of lattice groups on an absolute basis, without metric
      considerations. In contrast to long established but sophisticated methods for
      assessing the metric symmetry of a lattice, simple filtering of the symmetry
      operations from the predefined set is proposed. It is concluded that the space of
      symmetry matrices with elements from {0, +/-1} is the natural environment of
      lattice symmetries related to the reduced cells and that complete geometric
      characterization of matrices in the arithmetic holohedry provides a useful tool
      for solving practical lattice-related problems, especially in the context of
      lattice deformation.

PMID- 21844647
TI  - Direct methods: a paradox with regard to the convergence of random phase trials
      toward solutions.
AB  - A frustrating observation, based on an R(min) variance analysis within the 'shake
      and bake' framework of direct methods phasing, is described. The variance of
      R(min) can on occasion identify large subsets of phases that have a significantly
      lower mean phase error than the entire direct methods phase set of otherwise
      unsuccessful phasing trials for which the overall phase error occasionally dips
      below 75 or 80 degrees . This is the first time, other than for a handful of
      Sigma1 phase indications in optimal situations, that a priori phase estimates
      have been attained for large numbers of E values, prior to solving the structure.
      Although the a priori variance of R(min) is a useful tool for identifying such
      phases, the a posteriori phase refinement shifts indicated by its minimum often
      prevent a successful convergence to the solution. Similar efforts to encourage
      solution convergences in the realm of real space have also been discouraging.

PMID- 21844648
TI  - Mathematical aspects of molecular replacement. I. Algebraic properties of motion
      spaces.
AB  - Molecular replacement (MR) is a well established method for phasing of X-ray
      diffraction patterns for crystals composed of biological macromolecules of known
      chemical structure but unknown conformation. In MR, the starting point is known
      structural domains that are presumed to be similar in shape to those in the
      macromolecular structure which is to be determined. A search is then performed
      over positions and orientations of the known domains within a model of the
      crystallographic asymmetric unit so as to best match a computed diffraction
      pattern with experimental data. Unlike continuous rigid-body motions in Euclidean
      space and the discrete crystallographic space groups, the set of motions over
      which molecular replacement searches are performed does not form a group under
      the operation of composition, which is shown here to lack the associative
      property. However, the set of rigid-body motions in the asymmetric unit forms
      another mathematical structure called a quasigroup, which can be identified with
      right-coset spaces of the full group of rigid-body motions with respect to the
      chiral space group of the macromolecular crystal. The algebraic properties of
      this space of motions are articulated here.

PMID- 21844649
TI  - About the hybrid Fourier syntheses: a probabilistic approach.
AB  - The difference electron density has recently been revisited via the method of
      joint probability distribution functions [Burla et al. (2010). Acta Cryst. A 66,
      347-361]. New Fourier coefficients were devised which were the basis of a new ab
      initio method for the solution of the phase problem (i.e. VLD, vive la
      difference). In this paper we study the joint probability distribution functions
      P(F, F(p), F(Q)), where F(Q) is the structure factor corresponding to the ideal
      hybrid Fourier synthesis rho(Q) = taurho - omegarho(p) and tau and omega are any
      pair of real numbers. New Fourier coefficients for the calculations of any hybrid
      synthesis are obtained, and the properties of the corresponding electron-density
      maps are discussed. The first applications show the correctness of our
      theoretical approach and suggest possible applications in phasing procedures.

PMID- 21844650
TI  - Iteratively reweighted least squares in crystal structure refinements.
AB  - The use of robust techniques in crystal structure multipole refinements of small
      molecules as an alternative to the commonly adopted weighted least squares is
      presented and discussed. As is well known, the main disadvantage of least-squares
      fitting is its sensitivity to outliers. The elimination from the data set of the
      most aberrant reflections (due to both experimental errors and incompleteness of
      the model) is an effective practice that could yield satisfactory results, but it
      is often complicated in the presence of a great number of bad data points, whose
      one-by-one elimination could become unattainable. This problem can be
      circumvented by means of a robust least-squares regression that minimizes the
      influence of outliers. This work is aimed at showing the capability of a robust
      regression to achieve an higher reliability of the least-squares estimates with
      respect to the traditional weighted least-squares crystal structure refinement in
      terms of both accuracy and precision. The results can be considered encouraging
      and represent a starting point for future developments.

PMID- 21844651
TI  - Anisotropy of extinction: extrapolation to the kinematical limit by gamma-ray
      diffraction.
AB  - A direct experimental approach to the problem of anisotropic extinction is
      presented. Structure-factor measurements from a vanadium and a niobium crystal,
      performed with four gamma-ray wavelengths in the range 0.02-0.06 A, substantiate
      the adequacy of Zachariasen's theory [Acta Cryst. (1967), 23, 558-564] in high
      energy diffraction, which provides a theoretical basis for the extrapolation to
      zero extinction values. Fitting of the theoretical curve to the observed points,
      placed on a common scale, allows determination of the kinematical structure
      factor value without the need for a particular model of anisotropy in the mosaic
      structure.

PMID- 21844652
TI  - Radial integrals for the magnetic form factor of 5d transition elements.
AB  - The radial integrals, <linear span>j(L)<linear span>, where L = 0, 2, 4, for
      several electronic configurations in the 5d electrons of transition metal atoms
      and ions are calculated using radial wavefunctions from the pseudo-relativistic
      Hartree-Fock method in the Cowan program. The resultant values are fitted to
      Gaussian analytical expressions with four exponential terms, and the fitted
      coefficients are tabulated. This table can be used to interpret the magnetic form
      factor measurements for 5d transition metals.

PMID- 21844653
TI  - Bayesian algorithms for recovering structure from single-particle diffraction
      snapshots of unknown orientation: a comparison.
AB  - The advent of X-ray free-electron lasers promises the possibility to determine
      the structure of individual particles such as microcrystallites, viruses and
      biomolecules from single-shot diffraction snapshots obtained before the particle
      is destroyed by the intense femtosecond pulse. This program requires the ability
      to determine the orientation of the particle giving rise to each snapshot at
      signal levels as low as ~10(-2) photons per pixel. Two apparently different
      approaches have recently demonstrated this capability. Here we show they
      represent different implementations of the same fundamental approach, and
      identify the primary factors limiting their performance.

PMID- 21844654
TI  - Atomic resolution imaging using the real-space distribution of electrons
      scattered by a crystalline material.
AB  - We present an alternative atomic resolution incoherent imaging technique derived
      from scanning transmission electron microscopy (STEM) using detectors in real
      space, in contrast to conventional STEM that uses detectors in diffraction space.
      The images obtained from various specimens have a resolution comparable to
      conventional high-angle annular dark-field (HAADF) STEM with good contrast, which
      seems to be very robust with respect to thickness, focus and imaging conditions.
      The results of the simulations are consistent with the experimental results and
      support the interpretation of the real-space STEM image contrast as being a
      result of aberration-induced displacements of the high-angle scattered electrons.

PMID- 21844655
TI  - Genetic variation and haplotype structures of the glutathione S-transferase genes
      GSTA1 and GSTA2 in Japanese colorectal cancer patients.
AB  - Glutathione S-transferases (GSTs) play a vital role in the phase II
      biotransformation of many chemicals, including anticancer drugs. In this study,
      to elucidate the haplotype structures of the two closely related alpha-class
      genes GSTA1 and GSTA2, we screened for genetic variation in 214 Japanese
      colorectal cancer patients who received oxaliplatin-based chemotherapy. By direct
      resequencing of the 5'-flanking region, all the exons, and their flanking introns
      for 107 patients, 29 and 27 variants were identified in GSTA1 and GSTA2,
      respectively. The known functional single nucleotide polymorphisms (SNPs) 
      567T>G, -69C>T, and -52G>A in GSTA1*B were found at allele frequencies of 0.140.
      Of the four major GSTA2 allelic variants reported previously (GSTA2*A, *B, *C,
      and *E), only GSTA2*B (frequency = 0.154), *C (0.706), and *E (0.140) were
      detected. Following linkage disequilibrium analysis, haplotypes of both genes
      were separately estimated. Then, rapid genotyping methods for 7 and 6 SNPs
      tagging common haplotypes of GSTA1 and GSTA2, respectively, were developed using
      the single-base extension assay, and an additional 107 patients were genotyped.
      Finally, haplotype combinations of both genes were classified into 3 major types:
      GSTA1*A-GSTA2*C, GSTA1*A-GSTA2*B, and GSTA1*B-GSTA2*E. These findings will be
      useful in pharmacogenomic studies on xenobiotics including anticancer drugs.

PMID- 21844656
TI  - Metabolomic analysis reveals novel isoniazid metabolites and hydrazones in human
      urine.
AB  - Isoniazid (INH) is a first-line drug for tuberculosis control; the side effects
      of INH are thought to be associated with its metabolism, and this study was
      designed to globally characterize isoniazid metabolism. Metabolomic strategies
      were used to profile isoniazid metabolism in humans. Eight known and seven novel
      INH metabolites and hydrazones were identified in human urine. The novel products
      included two hydroxylated INH metabolites and five hydrazones. The two novel
      metabolites were determined as 2-oxo-1,2-dihydro-pyridine-4-carbohydrazide and
      isoniazid N-oxide. Five novel hydrazones were produced by condensation of
      isoniazid with keto acids that are intermediates in the metabolism of essential
      amino acids, namely, leucine and/or isoleucine, lysine, tyrosine, tryptophan, and
      phenylalanine. This study enhances our knowledge of isoniazid metabolism and
      disposition and may offer new avenues for investigating INH-induced toxicity.

PMID- 21844657
TI  - Expression of cytochromes p450 in fetal, infant, and juvenile liver of cynomolgus
      macaques.
AB  - Preclinical data of fetal, infant, and juvenile animals are important for the
      prediction of drug toxicity in fetuses and children. However, expression of drug
      metabolizing enzymes, including cytochromes P450 (CYPs), have not been fully
      investigated in fetal, infant, or juvenile liver of the cynomolgus macaque, an
      animal species important for preclinical studies. In this study, hepatic
      expression of 20 cynomolgus macaque CYPs (mfCYPs) in the CYP1-4 subfamilies that
      are relevant to drug metabolism was measured in fetuses, infants, and juveniles
      using DNA microarrays. Expression of most mfCYPs, including those moderately or
      abundantly expressed in postnatal livers such as mfCYP2A23, mfCYP2A24, mfCYP2B6,
      mfCYP2C9, mfCYP2C19, mfCYP2C76, mfCYP2D17, mfCYP2E1 mfCYP3A4, and mfCYP3A5, was
      much less abundant in fetal livers, but increased substantially after birth. In
      contrast, expression of mfCYP2C8 in fetal livers was not substantially different
      from postnatal livers. Since human CYP3A7 is expressed more abundantly in fetal
      livers than in adult livers, mfCYP3A7, an ortholog of human CYP3A7, was analyzed
      by quantitative polymerase chain reaction. Expression of mfCYP3A7 in fetal livers
      was much lower than that in postnatal livers, and greatly increased after birth,
      unlike the expression of human CYP3A7. These results indicate that expression of
      most mfCYPs examined was low in fetal livers, but increased greatly in postnatal
      livers, with a few exceptions such as mfCYP2C8.

PMID- 21844658
TI  - Discovery of genetic variants in CYP1D1: implication for functional integrity of
      CYP1D1 in cynomolgus macaques and rhesus macaques.
AB  - The cytochrome P450 (CYP) 1 family consists of the CYP1A, CYP1B, CYP1C, and CYP1D
      subfamilies. In humans, CYP1A1, CYP1A2, and CYP1B1 are expressed and encode
      functional enzymes, whereas CYP1D1P (formerly known as CYP1A8P) is present as a
      pseudogene as a result of five nonsense mutations in exon 2 and exon 7 of the
      putative coding region. We previously identified CYP1D1 in macaques and found
      that it was expressed and functional in liver. Moreover, the nonsense mutations
      in exon 2 and exon 7 were not found in the 20 cynomolgus macaques and 10 rhesus
      macaques analyzed in that previous study. These results raised the possibility
      that CYP1D1 is a functional gene in macaques; however, the possibility that
      nonsense mutations are present in other exons cannot be excluded. In this study,
      we sought to identify genetic variants of CYP1D1 in 63 cynomolgus macaques and 30
      rhesus macaques; we did not find nonsense mutations in any coding exon of the
      animals analyzed. Moreover, 15 of the 63 cynomolgus macaques were analyzed by
      quantitative polymerase chain reaction, confirming hepatic expression of CYP1D1
      in all 15 animals. These results suggest that CYP1D1 is most likely functional in
      cynomolgus macaques and rhesus macaques.

PMID- 21844659
TI  - Depleted leukocyte mitochondrial DNA copy number in metabolic syndrome.
AB  - AIMS: Metabolic syndrome (MetS) is characterized by a group of defects of
      metabolic origin which are possibly involved in mitochondrial DNA (mtDNA)
      alteration of mtDNA content [Lee et al. Exp Biol Med, 2007; 232(5):592-606]. The
      present study was undertaken to ascertain whether alteration of leukocyte mtDNA
      copy number is related to MetS. METHODS: Eighty non-MetS subjects and 50 subjects
      with MetS were recruited. The mtDNA copy number of leukocytes from each group of
      subjects was measured using quantitative polymerase chain reaction. RESULTS: The
      mtDNA copy number of leukocytes in subjects with MetS was significantly lower
      than that of non-MetS subjects. Depleted mtDNA copy number is correlated with
      lower plasma HDL, higher triglyceride, higher HOMA-IR and hypertension, and is
      even more sensitive to MetS criteria. CONCLUSIONS: Depleted leukocyte mtDNA copy
      number is related to the severity of MetS. Alteration of mtDNA copy number in
      leukocytes is proposed as a MetS biomarker involved in the bioenergetic change of
      mitochondria.

PMID- 21844660
TI  - Mean common or mean maximum carotid intima-media thickness as primary outcome in
      lipid-modifying intervention studies.
AB  - AIM: Carotid intima-media thickness (CIMT) measurements are used as a disease
      outcome in randomized controlled trials that assess the effects of lipid
      modifying treatment. It is unclear whether common CIMT or mean maximum CIMT
      should be used as the primary outcome. We directly compared both measurements
      using aspects that are of great importance in deciding which is most favorable
      for use in clinical trials. METHODS: A literature search was performed (PUBMED,
      up to March 31, 2008). Fifteen trials with lipid-modifying treatment were
      identified that had information on both outcome measures. Common CIMT and mean
      maximum CIMT were compared on reproducibility, strength of relation with LDL and
      HDL cholesterol and congruency of their results (harm/neutral/beneficial) with
      data from event trials. RESULTS: Findings showed that the reported
      reproducibility was high for both measurements, although a direct comparison was
      not possible. The relationship between the achieved LDL-C and HDL-C levels with
      CIMT progression was modest and showed no difference in magnitude between CIMT
      measurements. CIMT progression rates differed across carotid segments with the
      highest progression rates observed in the bifurcation segment. Treatment effects
      differed across carotid segments without a clear preference pattern. Trials using
      mean maximum CIMT progression more often (12 out of 15 studies) paralleled the
      findings of event trials in contrast to the mean common CIMT (11 out of 15
      studies), a difference not reaching statistical significance. CONCLUSIONS: Based
      on the literature, with equal results for reproducibility (assumed), lipid
      relationship and congruency with event findings, but with treatment effects that
      differ across carotid segments that can not be predicted, the mean maximum CIMT
      as the primary outcome may be preferred in trials on the impact of lipid
      modifying interventions. One advantage is that information on mean common CIMT
      can generally be obtained easily in protocols assessing mean maximum CIMT, but
      not the other way around.

PMID- 21844662
TI  - Editorial to the 25th anniversary issue in microbes and environments.

PMID- 21844664
TI  - [Why don't you reconfirm about "food safety"?].

PMID- 21844665
TI  - Common variants at the promoter region of the APOM confer a risk of rheumatoid
      arthritis.
AB  - Although the genetic component in the etiology of rheumatoid arthritis (RA) has
      been consistently suggested, many novel genetic loci remain to uncover. To
      identify RA risk loci, we performed a genome-wide association study (GWAS) with
      100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk
      locus (APOM gene) was re-sequenced to discover novel promoter and coding variants
      in a group of the subjects. Replication was performed with the independent case
      control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a
      novel SNP associated with RA at the APOM gene in the MHC class III region on
      6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 * 10-7). Three more
      polymorphisms were identified at the promoter region of the APOM by the re
      sequencing. For the replication, we genotyped the four SNP loci in the
      independent case-control set. The association of rs805297 identified by GWAS was
      successfully replicated (OR = 1.40, P = 6.65 * 10-5). The association became more
      significant in the combined analysis of discovery and replication sets (OR =
      1.56, P = 2.73 * 10-10). The individuals with the rs805297 risk allele (A) at the
      promoter region showed a significantly lower level of APOM expression compared
      with those with the protective allele (C) homozygote. In the logistic regressions
      by the phenotype status, the homozygote risk genotype (A/A) consistently showed
      higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These
      results indicate that APOM promoter polymorphisms are significantly associated
      with the susceptibility to RA.

PMID- 21844666
TI  - Genome wide association studies and prion disease.
AB  - Over the last decade remarkable advances in genotyping and sequencing technology
      have resulted in hundreds of novel gene associations with disease. These have
      typically involved high frequency alleles in common diseases and with the advent
      of next generation sequencing, disease causing recessive mutations in rare
      inherited syndromes. Here we discuss the impact of these advances and other gene
      discovery methods in the prion diseases. Several quantitative trait loci in mouse
      have been mapped and their human counterparts analysed (HECTD2, CPNE8); other
      candidate genes regions have been chosen for functional reasons (SPRN, CTSD).
      Human genome wide association has been done in variant Creutzfeldt-Jakob disease
      (CJD) and are ongoing in larger collections of sporadic CJD with findings around,
      but not clearly beyond, the levels of statistical significance required in these
      studies (THRB-RARB, STMN2). Future work will include closer integration of animal
      and human genetic studies, larger and combined genome wide association, analysis
      of structural genetic variantion and next generation sequencing studies involving
      the entire coding exome or genome.

PMID- 21844668
TI  - GM crops in Africa: challenges in Egypt.

PMID- 21844669
TI  - Rapeseed species and environmental concerns related to loss of seeds of
      genetically modified oilseed rape in Japan.
AB  - Feral rapeseed in Japan consists of Brassica rapa, B. juncea and B. napus, mostly
      produced by escape from crops. Brassica rapa and B. juncea were introduced from
      abroad long ago as leaf and root vegetables and as an oil crop and breeders have
      developed various cultivars. Brassica napus was introduced in the late 1800s,
      mainly as an oil crop. Rapeseed production in Japan is low, and most demand is
      met by imports from Canada (94.4% of the 2009 trade volume). Recently,
      spontaneous B. napus, including genetically modified (GM) herbicide-resistant
      individuals, has been detected along Japanese roads, probably originating from
      seeds lost during transportation of imports. As GM oilseed production increases
      abroad, the probability of escape of GM oilseed rape in Japan will increase,
      raising environmental biosafety concerns related to the impact of feral rapeseed
      on heirloom brassicaceous crops. In this paper, we review the history of rapeseed
      introduction in Japan and future concerns.

PMID- 21844670
TI  - Effect on soil chemistry of genetically modified (GM) vs. non-GM maize.
AB  - The effects of genetically modified (GM) maize (Zea mays L.) expressing the
      Bacillus thuringiensis Berliner Cry1Fa2 protein (Bt) and phosphinothricin or
      glyphosate herbicide tolerance on soil chemistry (organic matter, N, P, K and
      pH), compared with non-GM controls, were assessed in field and pot experiments.
      In the field experiment, NH(4)(+) was significantly higher in soil under the crop
      modified for herbicide tolerance compared to the control (mean values of 11 and
      9.6 mg N/kg respectively) while P was significantly higher in soil under the
      control compared to under the GM crop (mean values of 6.9 and 6.4 dg P/kg,
      respectively). No significant differences were found as a result of growing
      Bt/herbicide tolerant maize. In the pot experiment, using soils from three sites
      (Gongzhuling, Dehui and Huadian), significant effects of using Bt maize instead
      of conventional maize were found for all three soils. In the Gongzhuling soil, P
      was significantly higher in soil under the control compared to under the GM crop
      (mean values of 4.8 and 4.0 dg P/kg, respectively). For the Dehui soil, the pH
      was significantly higher in soil under the control compared to under the GM crop
      (mean values for {H(+)} of 1.1 and 2.4 MUM for the control and the GM crop
      respectively). In the Huadian soil, organic matter and total N were both higher
      in soil under the GM crop than under the control. For organic matter, the mean
      values were 3.0 and 2.9% for the GM crop and the control, respectively, while for
      total nitrogen the mean values were 2.02 and 1.96% for the GM crop and the
      control respectively. Our results indicate that growing GM crops instead of
      conventional crops may alter soil chemistry, but not greatly, and that effects
      will vary with both the specific genetic modification and the soil.

PMID- 21844671
TI  - Identification of maize embryo-preferred promoters suitable for high-level
      heterologous protein production.
AB  - The production of heterologous proteins in plants at levels consistent with
      commercialization of protein products requires molecular tools to ensure high
      level transgene expression. The identification of strong promoters, preferably
      specific to the target expression tissue, is a focus for improving foreign
      protein yields using transgenic cereals as a production system. Thus, there is a
      requirement for strong embryo preferred monocot promoters. We obtained the
      sequences of 500 randomly selected maize cDNA clones to determine gene expression
      profiles in embryo tissues at multiple stages during development. Promoters
      corresponding to the most abundant clones were identified and isolated. These
      promoters were fused to the b-glucuronidase reporter and their tissue specificity
      and developmental expression characteristics assessed in transgenic maize. All of
      the isolated promoters tested drove transgene expression predominantly in the
      embryo and were most active late in embryogenesis during storage protein
      deposition. One of the most active promoters assessed by transgene expression was
      associated with the globulin-1 protein. Sequence identified here extended
      approximately 1.6 kb distal to the previously identified extent of the globulin-1
      promoter, and this additional sequence boosted expression over two-fold. The
      extended globulin-1 promoter sequence isolated in this study has the potential
      for driving transgene expression at higher levels than those previously reported
      for cereals. Also, other highly active embryo promoters identified here offer
      opportunities to express multiple foreign proteins simultaneously at high levels
      in embryo tissues, while avoiding concerns over gene silencing due to the
      repeated use of a single promoter.

PMID- 21844672
TI  - GMOs in Africa: opportunities and challenges in South Africa.

PMID- 21844673
TI  - Towards much more efficient biofuel crops - can sugarcane pave the way?
AB  - A triple challenge will confront world plant production in a few forthcoming
      decades: population increase, worsening of growth conditions and changeover from
      fossil-based to renewable energy and raw materials. The challenge cannot be met
      without utilizing the best modern biological techniques, genetic modification
      included. In the current era of rapid environmental changes, plant breeding
      should take even greater responsibility for food, feed, fiber and fuels than in
      the past. There are good prospects for remarkable improvements in yield level and
      energy efficiency of plant production, as is exemplified with the cases of modern
      crop and especially sugarcane improvement in consideration. For example, sugar
      content, biomass yield, pest and disease resistance, environmental safety and
      resource use efficiency of biofuel crop production can be essentially improved on
      the basis of new genetic know-how and taking advantage of the richness of genetic
      resources available in the Plant Kingdom. In particular, the natural reservoir of
      10,000 wild grass species should be exploited in the purest way possible, by
      means of modern and precise GM methods. Consequently, our vital needs in biofuel
      crop production can be fulfilled without increasing crop production areas
      untenably at the expense of the remaining wilderness or compromising food
      security in the world.

PMID- 21844674
TI  - Genetic engineering for increasing fungal and bacterial disease resistance in
      crop plants.
AB  - We review the current and future potential of genetic engineering strategies used
      to make fungal and bacterial pathogen-resistant GM crops, illustrating different
      examples of the technologies and the potential benefits and short-falls of the
      strategies. There are well- established procedures for the production of
      transgenic plants with resistance towards these pathogens and considerable
      progress has been made using a range of new methodologies. There are no current
      commercially available transgenic plant species with increased resistance towards
      fungal and bacterial pathogens; only plants with increased resistance towards
      viruses are available. With an improved understanding of plant signaling pathways
      in response to a range of other pathogens, such as fungi, additional candidate
      genes for achieving resistance are being investigated. The potential for
      engineering plants for resistance against individual devastating diseases or for
      plants with resistance towards multiple pathogens is discussed in detail.

PMID- 21844675
TI  - RNA interference in designing transgenic crops.
AB  - RNA interference (RNAi) is a sequence specific gene silencing mechanism,
      triggered by the introduction of dsRNA leading to mRNA degradation. It helps in
      switching on and off the targeted gene, which might have significant impact in
      developmental biology. Discovery of RNAi represents one of the most promising and
      rapidly advancing frontiers in plant functional genomics and in crop improvement
      by plant metabolic engineering and also plays an important role in reduction of
      allergenicity by silencing specific plant allergens. In plants the RNAi
      technology has been employed successfully in improvement of several plant species
      by increasing their nutritional value, overall quality and by conferring
      resistance against pathogens and diseases. The review gives an insight to the
      perspective use of the technology in designing crops with innovation, to bring
      improvement to crop productivity and quality.

PMID- 21844676
TI  - Emergence of minor pests becoming major pests in GE cotton in China: what are the
      reasons? What are the alternatives practices to this change of status?
AB  - A recent study in China by Lu et al.(1) shows that populations of an occasional
      cotton pest, mirid bugs (Heteroptera: Miridae), increased following the
      introduction of genetically engineered (GE) cotton plants. The GE cotton produces
      a delta-endotoxin from the bacteria Bacillus thuringiensis (Bt) to control the
      cotton bollworm. Before the introduction of Bt cotton in China, mirid bugs were
      usually controlled by broad-spectrum pesticide sprays targeted against the cotton
      bollworm, Helicoverpa armigera Hubner (Lepidoptera: Noctuidae), the most
      important pest of cotton in China. The effectiveness of the control of H.
      armigera by Bt cotton cultivation has resulted in a decrease in the amount of
      insecticides used on Bt cotton compared to conventional cotton. This has led to a
      lack of control of mirids on Bt cotton due to the reduction in broad-spectrum
      insecticide use and consequently to a transformation of a minor pest to a main
      one. We discuss the scientific evidence available in the literature of this
      phenomenon. We examine the reasons of the emergence of minor pests to become
      major pests in Bt cotton in China and possible solutions to this change of
      status.

PMID- 21844677
TI  - Trait stacking in transgenic crops: challenges and opportunities.
AB  - In recent years, there has been a rapid increase in the planting of transgenic
      crops with stacked traits. Most of these products have been formed by
      conventional breeding, i.e. the crossing of transgenic plant (event) containing
      individual transgenes with other event(s) containing single or double transgenic
      traits. Many biotech companies are developing stacked trait products with
      increasing numbers of insect and herbicide tolerance genes for controlling a
      broad range of insect pests and weeds. There has also been an increase in
      development of technologies for molecular stacking of multiple traits in a single
      transgene locus. In this review we look at the status of stacked trait products,
      crop trait stacking technologies and the technical challenges we are facing. We
      also review recent progress in developing technology for assembling large
      transgene arrays in vitro (molecular stacks), their delivery to crop plants and
      issues they pose for transgene expression.

PMID- 21844678
TI  - Genetic modification of wood quality for second-generation biofuel production.
AB  - How the abundant tree biomass resources can be efficiently used for future
      biofuel production has attracted a great deal of interest and discussion in the
      past few years. Capable technologies are expected to be developed to realize the
      production of biofuel from wood biomass. A significant effort is put into the
      field of modifying wood properties of trees and simplifying the process of
      biomass-to-ethanol conversion, which includes mainly genetic engineering of
      lignin, cellulose and hemicellulose of woods. Current research in this field has
      achieved some promising results and opened up new opportunities to utilize wood
      biomass efficiently. This review will discuss the main developments in genetic
      modification of lignin, cellulose and hemicellulose biosynthesis in trees as well
      as other potential genetic technology of biofuel production from wood biomass.

PMID- 21844680
TI  - Expression, detection of candidate function and homology modeling for Vicia
      villosa ornithine delta-aminotransferase.
AB  - The accumulation of compatible solutes during stress in plant cell is well
      documented. Proline is one of these solutes which accumulate in the cytosol in
      response to drought or salinity stress in plants. Proline has several functions
      during stress just like osmotic adjustment, osmoprotection, free radical
      scavenger and antioxidant. Ornithine delta-aminotransferase (delta-OAT) is an
      important enzyme in proline biosynthetic pathway. It catalyzes the transamination
      of ornithine to pyrroline-5-carboxylate which can be reduced into proline.
      Expression of ornithine delta-aminotransferase gene isolated from Vicia villosa
      (VvOAT) showed protein with a molecular mass of 63 KDa which is compatible with
      the predicted mass and after VvOAT gene delivery into E. coli host HB101, VvOAT
      gene enhanced its salt tolerance. Homology modeling of VvOAT was performed based
      on the crystal structure of the ornithine delta-aminotransferase from humans (PDB
      code 2OATA). With this model, a flexible docking study with the substrate and
      inhibitors was performed. The results indicated that PHE170 and ASN171 in VvOAT
      are the important determinant residues in binding as they have strong hydrogen
      bonding contacts with the substrate and inhibitors. All the obtained results
      indicated the efficiency of utilizing this gene in conferring salt tolerance.

PMID- 21844683
TI  - GM in the media.

PMID- 21844681
TI  - Expression of S-adenosyl methionine decarboxylase gene for polyamine accumulation
      in Egyptian cotton Giza 88 and Giza 90.
AB  - Developing drought tolerance in Egyptian cotton varieties is a strategic goal
      considering the need to expand cotton cultivated area and water scarcity in the
      Nile valley. In the present study, increasing levels of polyamine accumulation
      via expressing S-adenosyl methionine decarboxylase (SAMDC) gene was the main
      goal. SAMDC cDNA isolated from Saccharomyces cerevisiae isolate was isolated and
      genetically engineered into Egyptian cotton varieties Giza 88 as an extra long
      staple and Giza 90 as a long staple by means of particle bombardment through
      meristem transformation.T(0) transgenic plants were screened using basta
      herbicide (200 mg/l). RT- PCR analysis was used to confirm gene expression while
      gene integration was confirmed by Southern blot analysis. Control plants from
      Giza 88 and Giza 90 were subjected to drought regime using different
      concentrations of PEG 6000 (2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 17%, and 20%) for 9
      hrs to record drought stress symptoms and determine the potential concentration
      level for inducing polyamine accumulation. 17% of PEG 6000 was considered the
      sublethal concentration showing drought stress symptoms and therefore was used as
      potential stress concentration for estimating the level for spermine accumulation
      in both control and transgenic Giza varieties. T(1) transgenic plants grown under
      induced drought stress regime were tested positive for gene integration and
      expression and subjected to HPLC analysis to determine levels of spermine as
      polyamine accumulated compound in response to drought stress regime. Elevated
      spermine accumulation in Egyptian cotton varieties Giza 88 and Giza 90, were
      compared as non transgenic plants grown under same induced drought conditions
      with T(1) transgenic plants using reverse-phase HPLC analysis. Elevated spermine
      accumulation expressing SAMDC gene reflect main cause for increasing drought
      tolerance in both transgenic varieties.

PMID- 21844684
TI  - Cell type-specific expression of sodium transporters improves salinity tolerance
      of rice.

PMID- 21844685
TI  - Vehicles and ways for efficient nuclear transformation in plants.
AB  - Transgenic science and technology are fundamental to the state-of-art plant
      molecular genetics and crop improvement. The new generation of technology
      endeavors to introduce genes 'stably' into 'site-specific' locations and in
      'single copy' without the integration of extraneous vector 'backbone' sequences
      or 'selectable markers'. Numerous plant transformation technologies have
      developed with the aim of achieving these objectives. Here we discuss some of
      these technologies, which can push the development of 'better transgenic plants
      with desirable characters only'.

PMID- 21844679
TI  - Maturity and ripening-stage specific modulation of tomato (Solanum lycopersicum)
      fruit transcriptome.
AB  - Tomato (Solanum lycopersicum) fruit is a model to study molecular basis of fleshy
      fruit development and ripening. We profiled gene expression during fruit
      development (immature green and mature green fruit) and ripening (breaker stage
      onwards) program to obtain a global perspective of genes whose expression is
      modulated at each stage of fruit development and ripening. A custom made cDNA
      macroarray containing cDNAs representing various metabolic pathways, defense,
      signaling, transcription, transport, cell structure and cell wall related
      functions was developed and used to quantify changes in the abundance of
      different transcripts. About 34 % of 1066 unique expressed sequence tags (ESTs)
      printed on the macroarray were differentially expressed during tomato fruit
      ripening. Out of these, 25 % genes classify under metabolism and protein
      biosynthesis/degradation related processes, while a significant proportion
      represented stress-responsive genes and about 44 % represented genes with unknown
      functions. RNA gel blot analysis validated changes in a few representative genes.
      Although the mature green fruit was found transcriptionally quiescent, the K
      means cluster analysis highlighted coordinated up or down regulation of genes
      during progressive ripening; emphasizing that ripening is a transcriptionally
      active process. Many stress-related genes were found up-regulated, suggesting
      their role in the fruit ripening program.

PMID- 21844686
TI  - Transgenic rice plants expressing cry1Ia5 gene are resistant to stem borer (Chilo
      agamemnon).
AB  - The stem borer, Chilo agamemnon Bles., is the most serious insect pest in rice
      fields of the Egyptian Nile Delta. To induce rice plant resistance to Chilo
      agamemnon, the cry1Ia5 gene was introduced to rice plants (Oryza sativa L.). The
      integration of the cry1Ia5 gene into the plant genome was confirmed using PCR and
      Southern blot analyses. The obtained plantlets were transferred to the greenhouse
      until seeds were collected. Northern blot analysis of the T1 plants confirmed the
      expression of the cry1Ia5 gene. The insecticidal activity of the transgenic
      plants against the rice stem borer Chilo agamemnon were tested. The third larval
      instars were fed on stem cuts from three transgenic lines (L1, L2 and L3) as well
      as cuts from the control (gfp-transgenic) plants for one week and the mortality
      percentage was daily recorded. Transgenic line-3 showed the highest mortality
      percentage after one day (50%) followed by L2 (25%) then L1 (0%). Two days post
      treatment the mortality percentage increased to 70, 45 and 25% for transgenic
      lines 1, 2 and 3 respectively. Mortality of 100% was recorded four days post
      treatment, while those fed on the gfp-transgenic rice (control) showed 0%
      mortality. Thus, transgenic plants showed high resistance to stem borers and can
      serve as a novel genetic resource in breeding programs. Transgenic plants
      expressing BT protein were normal in phenotype with as good seed setting as the
      nontransgenic control plants.

PMID- 21844687
TI  - Compositional safety of event DAS-40278-9 (AAD-1) herbicide-tolerant maize.
AB  - Event DAS-40278-9 maize expresses the aryloxyalkanoate dioxygenase-1 enzyme,
      which was originally identified in the soil bacterium Sphingobium
      herbicidovorans. This enzyme degrades 2,4-dichlorophenoxyacetic acid (2,4-D) and
      aryloxyphenoxypropionate herbicides (e.g., haloxyfop, cyhalofop, quizalofop,
      etc.); therefore, plants that contain this enzyme are tolerant to these
      herbicides. We employed the substantial equivalence approach to investigate the
      compositional safety of event DAS-40278-9 maize. A total of 82 different
      compositional analyses were conducted to evaluate the equivalence of event DAS
      40278-9 and conventional maize. Analyte levels within the transgenic entries were
      either within literature ranges for non-transgenic maize or statistically
      indistinguishable from the non-transgenic near-isogenic hybrid, thus indicating
      substantial equivalence between event DAS-40278-9 and its conventional
      counterpart. These results agree with dozens of published studies for other
      transgenic events where input traits were found to have a negligible effect on
      crop composition compared with traditional breeding methods.

PMID- 21844688
TI  - Development of a simple and effective protocol for Agrobacterium tumefaciens
      mediated leaf disc transformation of commercial tomato cultivars.
AB  - The transformation of tomato (Solanum lycopersicum) through Agrobacterium
      tumefaciens is still far from being routine, particularly when it comes to
      commercial varieties. In the present paper, we present an efficient and simple
      protocol for leaf disc transformation of three Vietnamese tomato cultivars (DM8,
      MTS, FM372C) by comparing shoot regeneration media for expanding leaves and
      examining different parameters of inoculation, co-culture and selection
      conditions. The present transformation method requires neither feeder layers of
      cell suspension cultures nor pre-culture. The data clearly show that appropriate
      cytokinin- and auxin combinations and concentrations provide competent tissues
      for transformation. Supplementing of 8 uM trans-zeatin and 5 uM indoleacetic acid
      (IAA) into pre-treatment, inoculation and co-culture media resulted in higher
      frequency of transformation and stronger GUS-expression than that of media
      supplemented with 4 uM trans-zeatin and 2 uM IAA. The experiments also exhibited
      that tomato leaf tissues were more sensitive to glufosinate after inoculation
      with Agrobacteria compared to the untreated controls, so a more sophisticated
      scheme for the glufosinate selection had to be established.

PMID- 21844689
TI  - Generation of transplastomic lettuce with enhanced growth and high yield.
AB  - We generated transplastomic lettuce plants expressing cyanobacterial fructose-1,6
      /sedoheptulose-1,7-bisphosphatase (FBP/SBPase) in chloroplasts. Their
      photosynthetic capacity and productivity were increased 1.3-fold and 1.6-fold,
      respectively, compared with control plants transformed with pRL200, indicating
      that the introduction of the enzyme affects the photosynthetic capacity and
      growth of lettuce plants at ambient CO(2) levels (360 ppm).

PMID- 21844690
TI  - Detection of genomic changes in transgenic Bt rice populations through genetic
      fingerprinting using amplified fragment length polymorphism (AFLP).
AB  - A highly precise molecular marker technique, Amplified Fragment Length
      Polymorphism (AFLP) was used to characterize the changes in genomic structure
      occurred due to introduction of foreign gene and/ or due to the induced tissue
      culture stress during the development of various transgenic Bt rice populations.
      The transgenic rice plants having complex to simple Bt gene and selectable marker
      gene organizations were selected from the six insect resistant Bt rice lines. Our
      results clearly demonstrate that integration pattern, extent of rearrangement of
      foreign DNA and method of transformation may influence the genomic changes in
      transgenic rice populations. Eleven of fourteen AFLP primer combinations tested,
      generated distinct scorable banding pattern, which were further used in this
      study. Three primer combinations E-TA / M-CTT (IRRI-NPT), E-AG / M-CAC (Tulasi)
      and E-AA / M-CAG (IR 68899B) produced only monomorphic bands in all the
      transgenic and control rice plants .A percentage of 0.61% of 430 million bases of
      haploid rice genome were examined by the use of 11 AFLP primer combinations
      employed in this study. The DNA fingerprints generated by AFLP analysis, of each
      Bt rice population was compared with their respective non-transgenic control and
      was found to be > 97% similar. This indicated that the introduction of Bt gene
      into the genome of six rice varieties showed few genomic changes. The comparison
      shows that fewer changes were observed among the transgenic plants developed by
      Agrobacterium infection than that of developed through particle bombardment.
      Transgene integration pattern and their copy number were associated with the
      extent of genomic changes observed in the transgenic Bt rice varieties. AFLP
      fingerprints of the six transgenic rice varieties evidenced few, but consistent
      polymorphic bands between the transgenic individuals with different PI values.
      Relationships among the transgenic populations with their control rice plants
      were expressed in the form of dendrograms.

PMID- 21844691
TI  - Novel Vip3A Bacillus thuringiensis (Bt) maize approaches high-dose efficacy
      against Helicoverpa zea (Lepidoptera: Noctuidae) under field conditions:
      Implications for resistance management.
AB  - Sweet corn, Zea mays L., transformed to express a novel vegetative insecticidal
      protein, Vip3A (event MIR162, Syngenta Seeds, Inc..), produced by the bacterium,
      Bacillus thuringiensis (Bt), was evaluated over four field seasons in Maryland
      and two field seasons in Minnesota for efficacy against the corn earworm,
      Helicoverpa zea (Boddie). Hybrids expressing the Vip3A protein and pyramided in
      hybrids also expressing the Cry1Ab Bt protein (event Bt11, ATTRIBUTE((r)),
      Syngenta Seeds, Inc.) were compared to hybrids expressing only Cry1Ab or to
      genetically similar non-Bt hybrids each year. In addition to H. zea efficacy,
      results for Ostrinia nubilalis (Hubner) and Spodoptera frugiperda (J.E. Smith)
      are presented. Over all years and locations, the non-Bt hybrids, without
      insecticide protection, averaged between 43 and 100% ears infested with a range
      of 0.24 to 1.74 H. zea larvae per ear. By comparison, in the pyramided Vip3A x
      Cry1Ab hybrids, no larvae were found and only minimal kernel damage (likely due
      to other insect pests) was recorded. Hybrids expressing only Cry1Ab incurred a
      moderate level of H. zea feeding damage, with surviving larvae mostly limited to
      the first or second instar as a result of previously documented growth inhibition
      from Cry1Ab. These results suggest that the Vip3A protein, pyramided with Cry1Ab,
      appears to provide the first "high-dose" under field conditions and will be
      valuable for ongoing resistance management.

PMID- 21844692
TI  - Stable integration and expression of a plant defensin in tomato confers
      resistance to fusarium wilt.
AB  - Plant defensins are small cysteine-rich peptides which belong to a group of
      pathogenasis related defense mechanism proteins. The proteins inhibit the growth
      of a broad range of microbes and are highly stable under extreme environmental
      stresses. Tomato cultivation is affected by fungal disease such as Fusarium wilt.
      In order to overcome fungal damages, transgenic tomato plants expressing the
      Medicago sativa defensin gene MsDef1 under the control of the CaMV 35S promoter
      were developed. The Fusarium-susceptible tomato (Lycobersicum esculentum Mill)
      cultivar CastleRock was used for transformation to acquire fungal resistance.
      Hypocotyl with a part of cotyledon (hypocotyledonary) for young tomato seedlings
      were used as an explant material and transformation was performed using the
      biolistic delivery system. Bombarded shoots were selected on regeneration medium
      supplemented with hygromycin and suitable concentrations of BA, zeatin ripozide
      and AgNO(3). Putative transgenic plantlets of T(0) were confirmed by PCR analysis
      using primers specific for the transgene and the transformation frequency
      obtained was 52.3%. Transformation and transcription of transgenes were confirmed
      in T(1) by PCR, Southern hybridizations, and reverse-transcription PCR (RT-PCR).
      The copy numbers of integrated transgene into tomato genome ranged between 1-3
      copies. Greenhouse bioassay was performed on the transgenic T(1) and T(2) young
      seedlings and non-transgenic controls by challenging with a vigorous isolate of
      the fungal pathogen Fusarium oxysporum f. sp. Lycopersici. The level of fungal
      infectivity was determined using RT-PCR with tomatinase specific primers.
      Transgenic lines were more resistant to infection by fusarium than the control
      plants. These results indicated that overexpressing defensins in transgenic
      plants confer resistance to fungal pathogens.

PMID- 21844693
TI  - GM in the media.

PMID- 21844694
TI  - Safety risks of cryptic reading frames and gene disruption due to crop
      transgenesis: what are the odds?

PMID- 21844695
TI  - Impact of GM crops on biodiversity.
AB  - The potential impact of GM crops on biodiversity has been a topic of interest
      both in general as well as specifically in the context of the Convention on
      Biological Diversity. Agricultural biodiversity has been defined at levels from
      genes to ecosystems that are involved or impacted by agricultural production
      (www.cbd.int/agro/whatis.shtml). After fifteen years of commercial cultivation, a
      substantial body of literature now exists addressing the potential impacts of GM
      crops on the environment. This review takes a biodiversity lens to this
      literature, considering the impacts at three levels: the crop, farm and landscape
      scales. Within that framework, this review covers potential impacts of the
      introduction of genetically engineered crops on: crop diversity, biodiversity of
      wild relatives, non-target soil organisms, weeds, land use, non-target above
      ground organisms, and area-wide pest suppression. The emphasis of the review is
      peer-reviewed literature that presents direct measures of impacts on
      biodiversity. In addition, possible impacts of changes in management practises
      such as tillage and pesticide use are also discussed to complement the literature
      on direct measures. The focus of the review is on technologies that have been
      commercialized somewhere in the world, while results may emanate from non
      adopting countries and regions. Overall, the review finds that currently
      commercialized GM crops have reduced the impacts of agriculture on biodiversity,
      through enhanced adoption of conservation tillage practices, reduction of
      insecticide use and use of more environmentally benign herbicides and increasing
      yields to alleviate pressure to convert additional land into agricultural use.

PMID- 21844696
TI  - Genetically engineered resistance to Plum pox virus infection in herbaceous and
      stone fruit hosts.
AB  - Plum pox virus (PPV), a Potyvirus, is the causal agent of sharka, the most
      detrimental viral disease affecting stone fruit trees. This review focuses on
      research carried out to obtain PPV- resistant transgenic plants and on how
      biotechnological strategies evolved in light of the scientific advances made
      during the last several years. Successful RNA silencing strategies that confer
      high level of resistance to strains of PPV have been developed and tested under
      laboratory and greenhouse conditions. Moreover, field tests showed that transgene
      mediated RNA silencing was effective in protecting plum plants against aphid
      mediated PPV infection. The new emerging biotechnological approaches for
      conferring PPV resistance are discussed.

PMID- 21844697
TI  - Global impact of biotech crops: environmental effects 1996-2009.
AB  - This paper updates the assessment of the impact commercialised agricultural
      biotechnology is having on global agriculture from an environmental perspective.
      It focuses on the impact of changes in pesticide use and greenhouse gas emissions
      arising from the use of biotech crops. The technology has reduced pesticide
      spraying by 393 million kg (-8.7%) and, as a result, decreased the environmental
      impact associated with herbicide and insecticide use on these crops (as measured
      by the indicator the Environmental Impact Quotient (EIQ)) by 17.1 %. The
      technology has also significantly reduced the release of greenhouse gas emissions
      from this cropping area, which, in 2009, was equivalent to removing 7.8 million
      cars from the roads.

PMID- 21844698
TI  - Production of early flowering transgenic barley expressing the early flowering
      allele of Cryptochrome2 gene.
AB  - This work was carried out in order to develop early flowering barley lines. These
      lines will be useful to producers by enabling multiple crops within a single
      season and increasing production. Transgenic barley plants containing the natural
      early flowering time AtCRY2 allele from the Cape Verde Island (Cvi) ecotype of
      Arabidopsis have been generated using biolistic transformation. Immature embryo
      derived calli of two commercially important barley cultivars (El-Dwaser and El
      Taif), were transformed using a pCAMBIA-2300 plasmid harboring a genomic fragment
      containing the AtCRY2-Cvi allele. Transformation was performed utilizing 600
      immature embryos for each cultivar. Stable transformation was confirmed in T 0
      and T 1 plants by using genomic PCR, RT-PCR and western blot analysis with AtCRY2
      specific primers and antibodies, respectively. The transformation efficiency was
      5.6% and 3.4% for El-Dwaser and El-Taif cultivars, respectively. Seeds from
      several T 1 lines were germinated on kanamycin plates and the lines that
      contained a single locus were selected for further evaluation. The transformed
      barley plants showed the specific AtCRY2-Cvi flowering phenotype, i.e. early
      flowering and day length insensitivity, compared to the non transgenic plants.
      The time to flowering in transgenic T 1 plants was assessed and two lines
      exhibited flowering more than 25 days earlier than the parental cultivars under
      short day conditions.

PMID- 21844699
TI  - Evaluation of salt tolerance in ectoine-transgenic tomato plants (Lycopersicon
      esculentum) in terms of photosynthesis, osmotic adjustment, and carbon
      partitioning.
AB  - Ectoine is a common compatible solute in halophilic bacteria. Its biosynthesis
      originates from L-aspartate beta-semialdehyde and requires three enzymes: L-2, 4
      diaminobutyric acid aminotransferase (gene: ect B), L-2,4-diaminobutyric acid
      acetyl transferase (gene: ect A) and L-ectoine synthase (gene: ect C).
      Genetically engineered tomato plants expressing the three H. elongata genes
      (ectA, ectB, and ectC) generated showed no phenotypic abnormality. Expression of
      the ectoine biosynthetic genes was detected in the T3 transgenic plants by
      Northern blot analysis. The ectoine accumulating T3 plants were evaluated for
      salt tolerance by examining their photosynthestic activity, osmotic adjustment
      and carbon partitioning. Nuclear magnetic resonance (NMR) detected the
      accumulation of ectoine. The concentration of ectoine increased with increasing
      salinity. The transgenic lines showed higher activities of peroxidase, while the
      malondialdehyde (MDA) concentration was decreased under salinity stress
      condition. In addition, preservation of higher rates of photosynthesis and turgor
      values as compared to control was evident. Within a week of ( 13) CO 2 feeding,
      salt application led to increases in the partitioning of ( 13) C into roots at
      the expense of ( 13) C in the other plant parts. These results suggest that under
      saline conditions ectoine synthesis is promoted in the roots of transgenic
      plants, leading to an acceleration of sink activity for photosynthate in the
      roots. Subsequently, root function such as water uptake is improved, compared
      with wild-type plants. In this way, the photosynthetic rate is increased through
      enhancement of cell membrane stability in oxidative conditions under salt stress.

PMID- 21844700
TI  - Transformation of the US bread wheat 'Butte 86' and silencing of omega-5 gliadin
      genes.
AB  - Complex groups of proteins determine the unique functional properties of wheat
      flour and are sometimes responsible for food intolerances and allergies in
      individuals that consume wheat products. Transgenic approaches can be used to
      explore the functions of different flour proteins, but are limited to the few
      wheat cultivars that can be transformed and also by the lack of detailed
      information about genes and proteins expressed in grain from those cultivars. The
      US bread wheat Butte 86 has been extensively characterized and a comprehensive
      proteome map was developed in which flour proteins were distinguished by mass
      spectrometry and associated with specific gene sequences. Here, this information
      has been used to design an RNA interference construct to silence the expression
      of genes encoding omega gliadins that trigger the food allergy wheat-dependent
      exercise-induced anaphylaxis (WDEIA). The construct was introduced into immature
      embryos from Butte 86 using biolistics and bialaphos-resistant plants were
      regenerated. Stable transformation and inheritance of the transgene were
      confirmed by PCR. Analysis of proteins in grain from transgenic plants
      demonstrated that the omega-5 gliadins were either absent or substantially
      reduced relative to non-transformed controls. The ability to genetically
      transform Butte 86 makes it possible to alter flour composition in a targeted
      manner in a commercial US wheat cultivar and should accelerate future research on
      flour quality and immunogenic potential.

PMID- 21844701
TI  - Development of multiplex and construct specific PCR assay for detection of cry2Ab
      transgene in genetically modified crops and product.
AB  - An efficient detection system for trait validation and screening of GMOs is a
      much sought after procedure, which could also help in regulatory compliance.
      Currently, in India, a number of cry2Ab transgene carrying GM crops are
      undergoing field trial i.e., MON15985 cotton, Bt rice, Bt okra, Bt corn, Bt
      brinjal, Bt potato and Bt tomato. In this study, we report a qualitative assay
      for detection for cry2Ab (326 bp). Further, the amplification compatibility with
      promoter, p35S (195 bp), terminator, t-nos (180 bp) and marker gene, npt II ( 215
      bp) was also confirmed using Bt cotton event MON15985 as reference material. The
      detection sensitivity was 0.1% that is far below the requirement of the stringent
      European Union (EU) regulations of 0.9%. The target DNA when spiked with either
      MECH-12 (cry1Ac), RR-soya (epsps) or MON-810 (cry1Ab) showed no inhibitory effect
      on cry2Ab detection. Moreover, the cry2Ab specific transgene construct (1.9 kb)
      was amplified and its identity confirmed by a nested PCR. Hence, a comprehensive
      multiplex PCR method for detection of cry2Ab gene in a GM crop/products was
      established. This is possibly a first report showing concurrent amplification of
      cry2Ab transgene, promoter, terminator and marker gene.

PMID- 21844702
TI  - Genital chlamydia, genital herpes, Trichomonas vaginalis and gonorrhea
      prevalence, and risk factors among nearly 70,000 randomly selected women in 4
      Nordic countries.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of women reporting
      ever having genital chlamydia, genital herpes, Trichomonas vaginalis, and
      gonorrhea, and to identify factors associated with each of these sexually
      transmitted infections (STIs). METHODS: The study was based on a large cross
      sectional survey conducted in 2004-2005 among randomly sampled women (18-45
      years) from the computerized population registries in Denmark, Iceland, Norway,
      and Sweden. A total of 69,567 women were included in the study. RESULTS: The
      overall prevalence in Denmark, Iceland, Norway, and Sweden was 1.5% for reporting
      ever having had Trichomonas vaginalis, 1.9% for gonorrhea, 4.8% for genital
      herpes, and 17.0% for genital chlamydia. The prevalence of each of these STIs
      varied with birth cohort and country. In addition, they were strongly associated
      with lifetime number of partners and having a previous diagnosis of another
      sexually transmitted infection. Moreover, a diagnosis of genital chlamydia or
      gonorrhea was associated with early age at first intercourse and smoking
      initiation. Finally, reporting genital chlamydia was associated with early age at
      drinking initiation, and ever use of hormonal contraceptives and condoms.
      CONCLUSION: Genital chlamydia occurs frequently among women in the Nordic
      countries. Risk-taking behavior, particularly sexual behavior, is strongly
      associated with STIs, which suggest that further information is needed about STIs
      and their consequences, targeting high-risk groups. There is also a need for
      continued monitoring of STIs in order to follow the prevalence and to gain
      further knowledge about risk factors.

PMID- 21844704
TI  - Current world literature.

PMID- 21844707
TI  - The epidemic of type 1 diabetes: what is it telling us?
AB  - PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disorder which affects
      millions around the world. The incidence of T1D in children is increasing
      worldwide at a rate that cannot be explained by genetics alone. This review
      explores the recent research regarding possible causes of this epidemic. RECENT
      FINDINGS: Investigation into T1D epidemiology has recently focused on several
      hypotheses. These theories include the role of infections, early childhood diet,
      vitamin D exposure, environmental pollutants, increased height velocity, obesity,
      and insulin resistance in the risk for T1D. Over the past year, the evidence has
      strengthened for early childhood infections, dietary proteins, and insulin
      resistance as risk factors for T1D, but not for vitamin D exposure or
      environmental pollutants. SUMMARY: Investigation into the source of the current
      epidemic of T1D has shed light on several possible causes, but has not provided
      definitive answers, yet.

PMID- 21844706
TI  - 2011 Update: antigen-specific therapy in type 1 diabetes.
AB  - PURPOSE OF REVIEW: To update on the clinical trials using antigen-specific
      therapies in autoimmune diabetes. RECENT FINDINGS: Type 1 diabetes is now a
      predictable disease with the measurement of islet autoantibodies, and the
      incidence is increasing dramatically. Well tolerated and effective interventions
      are needed to stop the underlying autoimmune destruction of insulin-producing
      beta cells. Beta-cell antigens, insulin and glutamic acid decarboxylase, are
      being used to preserve endogenous insulin production in individuals with new
      onset diabetes and to prevent diabetes. The results of antigen-specific immune
      intervention trials are reviewed and consideration is given to future directions
      for inducing tolerance in type 1 diabetes. SUMMARY: Antigen-specific immune
      therapies act by enhancing regulatory T cell function, in animal models often
      locally and selectively in islets or pancreatic lymph nodes while inhibiting
      effector T cells. This therapeutic pathway provides a safe treatment to preserve
      beta cell function in new-onset diabetic individuals with the GAD-Alum vaccine
      being the most extensively studied therapy. Insulin is being used in many forms
      to prevent diabetes and stop the underlying autoimmune process. For the future,
      combination immune therapies targeting different pathways in the immune system
      will be needed to effectively induce sustained tolerance in type 1 diabetes.

PMID- 21844708
TI  - Review on monogenic diabetes.
AB  - PURPOSE OF REVIEW: The goal of this review is to provide an update on the
      different forms of monogenic diabetes, including maturity-onset diabetes of the
      young (MODY) and neonatal diabetes (permanent and transient neonatal diabetes).
      RECENT FINDINGS: Monogenic diabetes accounts for approximately 1-2% of diabetes
      cases and results from mutations that primarily reduce beta-cell function.
      Individuals with islet autoantibody negative youth-onset forms of diabetes should
      be evaluated for either glucokinase-MODY or transcription factors MODY. The mild
      fasting hyperglycemia found in glucokinase-MODY typically does not necessitate
      pharmacological treatment, whereas patients with MODY caused by transcription
      factor mutations can often be successfully treated with low-dose sulfonylurea.
      Neonatal diabetes is defined as diabetes onset within the first 6 months of life
      and most individuals with permanent neonatal diabetes can be treated with high
      dose sulfonylurea. SUMMARY: The discovery of the genetic cause of monogenic
      diabetes has greatly advanced our understanding and management of these uncommon
      forms of diabetes.

PMID- 21844709
TI  - Update on the withdrawal of dopamine agonists in patients with
      hyperprolactinemia.
AB  - PURPOSE OF REVIEW: Despite the widespread use of dopamine agonists for patients
      with prolactinomas and symptomatic idiopathic hyperprolactinemia for many
      decades, the optimal treatment strategy and duration of treatment is still not
      evident. This review highlights the effects of dopamine agonist withdrawal in
      patients with idiopathic hyperprolactinemia and prolactinomas in detail,
      including the factors influencing the success of treatment outcome. RECENT
      FINDINGS: It appeared that a subgroup of patients with a high likelihood of
      achieving remission could be identified on clinical criteria, which were
      incorporated in the Pituitary Society 2006 consensus guidelines. A recent
      systematic review and meta-analysis, however, demonstrated that the pooled
      proportion of patients with persisting normoprolactinemia after dopamine agonist
      withdrawal was only 21%, with a higher treatment success in idiopathic
      hyperprolactinemia (32%), compared with both microprolactinomas (21%) and
      macroprolactinomas (16%). In a random effects meta-regression, longer treatment
      duration was associated with treatment success. The probability of treatment
      success was highest when cabergoline was used for at least 2 years.
      Recommendations have now been adjusted accordingly in the 2011 Endocrine Society
      Practical guideline. SUMMARY: Hyperprolactinemia will recur after dopamine
      agonist withdrawal in a considerable proportion of patients, but not all dopamine
      agonists have comparable efficacy. The optimal withdrawal strategy still needs to
      be determined in further studies.

PMID- 21844710
TI  - The role of interventional venous sampling in localising neuroendocrine tumours.
AB  - PURPOSE OF REVIEW: This review focuses on the role of interventional venous
      sampling in the diagnosis and localization of neuroendocrine tumours (NETs), and
      its role in relation to conventional and novel imaging techniques. RECENT
      FINDINGS: Imaging of NETs has evolved together with advances in imaging
      technology. Imaging localization plays an important role in the subsequent
      management of these tumours. This article provides an overview of the application
      of venous sampling in the localization of NETs, presented with current evidence
      to support its continued role in the diagnostic work-up of pituitary,
      parathyroid, pancreatic, adrenal and ovarian endocrine disease. SUMMARY:
      Interventional venous sampling continues to be a highly sensitive modality in the
      localization of NETs. Although significant advances in noninvasive anatomic and
      functional imaging modalities have reduced the reliance of this well established
      technique, the latest literature continues to support its important role in the
      diagnostic armament of these unique and rare tumours.

PMID- 21844711
TI  - Recent advances in pituitary tumor management.
AB  - PURPOSE OF REVIEW: Advances in the neurosurgical management of pituitary tumors
      have included the refinement of surgical access and significant progress in
      navigation technology to help further reduce morbidity and improve outcome.
      Similarly, stereotactic radiosurgery has evolved to become an integral part in
      pituitary tumors not amenable to medical or surgical treatment. RECENT FINDINGS:
      The evolution of minimally invasive surgery has evolved toward endoscopic versus
      microscopic trans-sphenoidal approaches for pituitary tumors. Debate exists
      regarding each approach, with advocates for both championing their cause.
      Stereotactic and fractional radiosurgery have been shown to be a safe and
      effective means of controlling tumor growth and ensuring hormonal stabilization,
      with longer-term data available for GammaKnife compared with CyberKnife. SUMMARY:
      The advances in trans-sphenoidal surgical approaches, navigation technological
      improvements and the current results of stereotactic radiosurgery are discussed.

PMID- 21844712
TI  - Current world literature.

PMID- 21844713
TI  - Sexually transmitted infections and hepatitis in men with a history of
      incarceration.
AB  - BACKGROUND: Men entering correctional facilities have high rates of human
      immunodeficiency virus, sexually transmitted infections (STI), and hepatitis.
      Many prisons offer screening, treatment, and vaccination services; however,
      little is known about the rates of these infections in men after release to the
      community. METHODS: Young men were recruited from prisons in Mississippi, Rhode
      Island, and Wisconsin as part of a human immunodeficiency virus/STI/hepatitis
      intervention study. Participants were offered screening for Neisseria gonorrhoeae
      (GC), Chlamydia trachomatis, trichomoniasis, syphilis, hepatitis B (HBV) and C
      (HCV) 6 months after release. Logistic regression was performed to identify
      associations with prevalent infections. RESULTS: Of 248 eligible men, 178 (71.8%)
      participated. Their mean age was 22.5 years, and 92% reported multiple lifetime
      incarcerations. At 6-month postrelease, 79% reported unprotected vaginal or anal
      sex, and 26% tested positive for 1 or more infections (GC, 1%; C. trachomatis,
      12%; trichomoniasis, 8%; syphilis, 0%; HCV, 6%; HBV, 1%). Of all, 55% were
      susceptible to HBV infection. Active STI (GC, C. trachomatis, or trichomoniasis)
      was associated with less education (odds ratios [OR], 2.25; P < 0.05). HCV
      infection was associated with injection drug use (OR, 69.70; P < 0.05) and being
      white (OR, 7.54; P < 0.05). HBV susceptibility was associated with older age (OR,
      3.02; P < 0.05), more education (OR, 2.39; P < 0.05), or incarceration in
      Mississippi (OR, 6.69; P < 0.05) or Rhode Island (OR, 2.84; P < 0.05).
      CONCLUSIONS: Effective screening and prevention programs are needed for this
      population before and after release from custody to prevent acquisition and
      further transmission of these infections.

PMID- 21844714
TI  - High Chlamydia and gonorrhea incidence and reinfection among performers in the
      adult film industry.
AB  - BACKGROUND: Adult film industry (AFI) performers engage in unprotected oral,
      vaginal, and anal sex with multiple partners, increasing the likelihood of
      acquisition and transmission of human immunodeficiency virus and other sexually
      transmitted diseases. Current industry practice does not require condom use;
      instead it relies upon limited testing. We sought to estimate the annual
      cumulative incidence of chlamydia (CT) and gonorrhea (GC) and assess the rate of
      reinfection among AFI performers. METHODS: We retrieved all CT and GC cases
      diagnosed among performers between 2004 and 2008 in Los Angeles, CA and reported
      to the health department surveillance registry. Using 2008 data, we estimated
      ranges for CT and GC annual cumulative incidences based on assumptions of the
      population size of performers. For cases reported between 2004 and 2007, we
      determined the CT and/or GC reinfection rate within 1 year. RESULTS: Lower bounds
      for the annual cumulative incidences of CT and GC among AFI performers were
      estimated to be 14.3% and 5.1%, respectively. The reinfection rate within 1 year
      was 26.1%. Female performers were 27% more likely to be reinfected as compared
      with male performers (prevalence ratio, 1.27; 95% confidence interval, 1.09
      1.48). CONCLUSION: CT and GC infections are common and recurrent among
      performers. Control strategies, including promotion of condom use, are needed to
      protect workers in this industry, as testing alone will not effectively prevent
      workplace acquisition and transmission. Additional legislation that places more
      responsibility on the production companies is needed to ensure the safety and
      health of performers.

PMID- 21844715
TI  - Prevalence of bacterial vaginosis and vulvovaginal candidiasis mixed infection in
      a southeastern american STD clinic.
AB  - Bacterial vaginosis (BV) was diagnosed in 72.5% of female participants. Among
      women with BV, 33.1% were colonized with yeast. Vulvovaginal candidiasis was
      observed in 15.7% of participants irrespective of BV status. Overall, the
      prevalence of BV/vulvovaginal candidiasis mixed infections among young women was
      observed to be 4.4%.

PMID- 21844716
TI  - Couples, sexual networks, populations: implications for use of coitus
      interruptus.

PMID- 21844717
TI  - Letter to the Editor from Planned Parenthood Federation of America's National
      Director of Education Initiatives.

PMID- 21844718
TI  - Will chlamydia screening reach young people in deprived areas in England?
      Baseline analysis of the English National Chlamydia Screening Programme delivery
      in 2008.
AB  - BACKGROUND: The National Chlamydia Screening Programme (NCSP) was established in
      England to control chlamydia in people <25 years. This study examined variations
      in NCSP delivery in 2008, its first full year of national coverage, by comparing
      the distribution of screening venues and coverage with the risk of testing
      positive in men and women by socioeconomic circumstances (SEC) and age. METHODS:
      A total of 550,000 NCSP screening records from 2008 were linked to the Index of
      Multiple Deprivation 2007. NCSP provision (venues/1000 population aged 13-24
      years) was examined by SEC. NCSP coverage (tests/target population) and
      chlamydial positivity (positive results/[positive + negative results]) were
      examined separately in men and women by SEC and age. Odds ratios for positivity
      were calculated, adjusted for socioeconomic quintile, age, ethnicity, behavior,
      and screening provider. RESULTS: NCSP coverage was just 4.1% (95% confidence
      interval [CI]: 4.0-4.1) in men and 9.6% (95% CI: 9.5-9.6) in women. Screening
      provision and coverage were highest in more socioeconomically deprived areas
      where chlamydia positivity was also highest. The adjusted odds for testing
      positive in the most deprived areas was 1.4 (95% CI: 1.3-1.5) times higher in men
      and 1.4 (95% CI: 1.4-1.5) times higher in women than the least deprived areas.
      CONCLUSIONS: In the first year in which all areas delivered screening, the NCSP's
      total coverage was low, particularly in men. However, coverage was higher in
      deprived populations, who were also at increased risk of testing positive for
      infection. This analysis provides a baseline by which to monitor social
      variations in NCSP delivery as coverage expands.

PMID- 21844719
TI  - Loss to follow-up among adults attending human immunodeficiency virus services in
      England, Wales, and Northern Ireland.
AB  - AIM: To assess the extent to which human immunodeficiency virus (HIV)-diagnosed
      adults attending HIV-services in England, Wales, and Northern Ireland are lost to
      follow-up or attend services intermittently. METHODS: A cohort of HIV-diagnosed
      adults was created by linking records across the 1998 to 2007 national annual
      Survey of Prevalent HIV Infections Diagnosed. The records were also linked to the
      national HIV and acquired immune deficiency syndrome New Diagnoses Database (n =
      61,495) and to Office for National Statistics death records. Patterns of HIV
      service attendance were analyzed. RESULTS: On average, 90% of adults attending
      HIV-services in any one year attended the following year. Nearly 5% of adults
      attending services in any one year were lost to follow-up, a further 4%
      subsequently attended services intermittently, whereas less than 2% died.
      Cumulatively, 19% of adults seen for HIV care between 1998 and 2006 were lost to
      follow-up by the end of 2007. Factors associated with loss to follow-up included
      being the following: female; aged 15 to 34 years; black-African or "other"
      ethnicity; not on antiretroviral therapy; recently diagnosed; and infected
      outside the United Kingdom. CONCLUSIONS: Although the majority of HIV-diagnosed
      adults in England, Wales, and Northern Ireland attended HIV-services regularly,
      cumulatively nearly 1 in 5 adults were lost to follow-up between 1998 and 2007.
      Innovative strategies focusing on those most likely to drop out of regular care
      should be developed to maintain regular service engagement and to ensure optimal
      care.

PMID- 21844720
TI  - Examining the components of population-level sexual behavior trends from 1993 to
      2007 in an open ugandan cohort.
AB  - INTRODUCTION: Sexual behavior changes are widely cited as contributing factors to
      sexually transmitted disease trends. We explore a rarely examined aspect of
      behavior trends in an open cohort--the relative impact of individuals' changing
      reported behavior versus new responses due to a changing respondent base.
      METHODS: Respondents from an open cohort in Uganda annually answer questions on
      sexual behavior. We describe the impacts on behavior trends of: respondents'
      changing reported behavior, migration, mortality, changing eligibility for
      indicator inclusion, changing survey participation, and misreporting. We report
      contributions to trends on the following factors: condom use, ever had sex, age
      at first sex, and number of sexual partners and casual partners. RESULTS: Main
      trend contributions varied by indicator. Condom use trends were influenced by
      individuals' changing responses and by increasing condom use among in-migrants
      and newly interviewed people. Sexual partners were driven by fewer partners among
      newly interviewed people, although increase of partners in 1999, 2004, and 2006
      stemmed mainly from people changing answers. Thirty-nine percent of responses to
      age at first sex among 17- to 20-year-olds were inconsistent--different ages in
      different years. Early trends in the factor "ever had sex" among 15- to 19-year
      olds were driven by people changing their answers--including ever to never, an
      impossible sequence. Comparing behavior in one year to mortality in the next, we
      found little evidence of higher mortality among higher risk takers. DISCUSSION:
      In an open cohort, various factors contribute to sexual behavior trends. When
      reporting sexual behavior trends, researchers should acknowledge the contributing
      factors and attempt to separate the role of interindividual versus
      intraindividual changes.

PMID- 21844721
TI  - Population-based surveillance for neonatal herpes in New York City, April 2006
      September 2010.
AB  - BACKGROUND: Population-based data for neonatal herpes simplex virus (HSV)
      infection are needed to describe disease burden and to develop and evaluate
      prevention strategies. METHODS: From April 2006 to September 2010, routine
      population-based surveillance was conducted using mandated provider and
      laboratory reports of neonatal HSV diagnoses and test results for New York City
      resident infants aged <=60 days. Case investigations, including provider
      interviews and review of infant and maternal medical charts and vital records,
      were performed. Hospital discharge data were analyzed and compared with
      surveillance data findings. RESULTS: Between April 2006 and September 2010, New
      York City neonatal HSV surveillance detected 76 cases, for an average incidence
      of 13.3/100,000 (1/7519) live births. Median annual incidence of neonatal HSV
      estimated from administrative data for 1997 to 2008 was 11.8/100,000. Among
      surveillance cases, 90.8% (69/76) were laboratory confirmed. Among these, 40.6%
      (28/69) were HSV-1; 39.1% (27/69) were HSV-2; and 20.3% (14/69) were untyped. The
      overall case-fatality rate was 17.1% (13/76). Five cases were detected among
      infants aged >42 days. In all, 80% (20/25) of the case-infants delivered by
      cesarean section were known to have obstetric interventions that could have
      increased risk of neonatal HSV transmission to the infant before delivery. Over
      half (68%, or 52/76) of all cases lacked timely or ideal diagnostics or
      treatment. CONCLUSIONS: Administrative data may be an adequate and relatively
      inexpensive source for assessing neonatal HSV burden, although they lack the
      detail and timeliness of surveillance. Prevention strategies should address HSV
      1. Incubation periods might be longer than expected for neonatal HSV. Cesarean
      delivery might not be protective if preceded by invasive procedures. Provider
      education is needed to raise awareness of neonatal HSV and to assure appropriate
      testing and treatment.

PMID- 21844722
TI  - Monitoring trends and epidemiologic correlates of neonatal herpes: is mandated
      case reporting the answer?

PMID- 21844723
TI  - Barriers to HIV testing among HIV/AIDS concurrently diagnosed persons in New York
      City.
AB  - OBJECTIVES: To assess barriers to human immunodeficiency virus (HIV) testing,
      health care contacts history, and HIV testing history among patients diagnosed
      concurrently with HIV and acquired immunodeficiency syndrome (AIDS). METHODS: We
      surveyed patients concurrently diagnosed with HIV/AIDS who had participated in
      the partner notification program of the New York City Department of Health and
      Mental Hygiene, between January 2008 and December 2008. RESULTS: The most common
      reason interviewees volunteered for delaying testing (64%) was that they did not
      believe they were at risk for HIV. When read a list of potential barriers, 69% of
      interviewees replied affirmatively that they did not test for HIV because they
      did not believe they were at risk, and 52% replied affirmatively that they did
      not test because they thought their behaviors kept them safe from getting HIV.
      Half of all interviewees reported having insurance during part or all of the year
      before they were diagnosed with HIV/AIDS, and 70% had at least 1 health care
      visit in the year before they were diagnosed with HIV/AIDS. CONCLUSIONS: A lack
      of perception of risk was the most common reason for not testing for HIV sooner
      among these concurrently diagnosed patients. The majority of these patients were
      accessing medical care, indicating that this population could have benefited from
      routine HIV testing.

PMID- 21844724
TI  - Implementation of expedited partner therapy among women with chlamydia infection
      at an urban family planning clinic.
AB  - BACKGROUND: Reinfection with chlamydia is common and expedited partner therapy
      (EPT) decreases reinfection in clinical trials. Many clinical practices have
      adopted EPT as the principal treatment strategy for male partners. Little is
      known about its application and effectiveness in a community setting. METHODS: We
      conducted a retrospective cohort study of all female patients with chlamydia
      between 2004 and 2005 at a university-based family planning clinic. We abstracted
      demographic and clinical information from charts, including partner treatment
      strategy. We collected data on reinfection at 3 months and 1 year using a
      computerized database of laboratory results within the medical system. RESULTS:
      During 2004 to 2005, 499 women tested positive for chlamydia. Of the 466 women
      treated, EPT was given to 323 women (69.3%). No baseline characteristics were
      associated with EPT provision. Only 40% of women returned for a retest within 3
      months. Reinfection at 3 months was 4.8%. Patients who received EPT were as
      likely to be reinfected than those who did not receive EPT (odds ratio, 1.6; 95%
      confidence interval, 0.2-13.7). CONCLUSIONS: Although EPT was not associated with
      decreased reinfection, it remains an option for partner treatment. This study
      highlights the ongoing need to address compliance with retesting within 3 months.

PMID- 21844725
TI  - Human immunodeficiency virus, sexually transmitted infections, and risk behaviors
      among clients of sex workers in Guatemala: are they a bridge in human
      immunodeficiency virus transmission?
AB  - OBJECTIVES: Clients of female sex workers (FSWs) are an important target group
      for human immunodeficiency virus/sexually transmitted infection (HIV/STI)
      prevention. This study aimed to estimate their HIV and other STI prevalence,
      examine their risk behaviors, and evaluate their role as a bridge population in
      the spread of HIV/STIs. METHODS: A cross-sectional study was performed among 553
      clients recruited in commercial sex sites in the province of Escuintla,
      Guatemala. They were interviewed and tested for HIV and other STIs. RESULTS: Half
      of the clients who were approached refused participation. Median age was 28.9
      years; 57.7% had a regular partner, of whom, 10.1% had concurrent noncommercial
      partnerships. Consistent condom use with FSWs and regular partners was 72.5% and
      17.1%, respectively. Approximately 18% formed a bridge, and 40.0% a potential
      bridge. Among those who provided samples (70.5% provided a blood sample and
      89.7%, urine sample), prevalence of HIV, syphilis, gonorrhea, chlamydia, and
      herpes simplex virus 2 was 1.5%, 1.0%, 0.8%, 5.5%, and 3.4%, respectively.
      Unprotected sex with FSWs and drug use just before sex were risk factors for
      having any STI (9.8% of participants). Bridge clients were significantly less
      educated, more employed, paid lower prices to the FSW just visited, and had a
      previous STI. CONCLUSIONS: There is a relatively high prevalence of HIV in
      clients compared to national estimates, and a substantial proportion of them act
      as a bridge for HIV/STI transmission between FSWs and the general population in
      Escuintla. Given that this is fuelling the current HIV epidemic, preventive
      interventions addressing this hard-to-reach group are urgently required.

PMID- 21844726
TI  - Chlamydia trachomatis infection among 15- to 35-year-olds in Baltimore, MD.
AB  - BACKGROUND: Chlamydia trachomatis (Ct) is the most frequently reported infectious
      disease in the United States. This article reports population and subpopulation
      prevalence estimates of Ct and correlates of infection among 15- to 35-year-olds
      in Baltimore, MD. METHODS: The Monitoring STIs Survey Program (MSSP) monitored
      sexually transmitted infection (STI) prevalence among probability samples of
      residents of Baltimore, a city with high STI rates. MSSP respondents completed
      telephone audio computer-assisted self-interviews and provided biospecimens for
      STI testing. RESULTS: Among 2120 Baltimore residents aged 15 to 35 years, the
      estimated prevalence of chlamydia was 3.9% (95% confidence interval [CI]: 2.8,
      5.0). Prevalence was 5.8% (95% CI: 4.1, 7.6) among black MSSP respondents versus
      0.7% (95% CI: 0.0, 1.4) among nonblack respondents; all but 4 infections detected
      were among black respondents. Sexual behaviors and other factors associated with
      infection were far more prevalent among black than nonblack Baltimore residents.
      Racial disparities persisted after adjustment for sociodemographic, behavioral,
      and health factors. CONCLUSION: The MSSP highlights a higher Ct prevalence among
      young people in Baltimore than in the United States overall, with notable racial
      disparities in infection and associated risk behaviors. Public health efforts are
      needed to improve the diagnosis and treatment of asymptomatic infections in this
      population.

PMID- 21844727
TI  - Resistance to azithromycin of Neisseria gonorrhoeae isolates from 2 cities in
      China.
AB  - BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae (NG) is a public
      health concern globally, and azithromycin-resistant NG isolates have been
      identified in many countries. This study aimed to investigate azithromycin
      susceptibility in NG and to genetically characterize the azithromycin-resistant
      isolates identified in 2 cities in China. METHODS: NG isolates (n = 318) were
      cultured from patients attending 2 sexually transmitted infection clinics in
      Nanjing and Chongqing, China, between 2008 and 2009. Minimum inhibitory
      concentration (MIC) of azithromycin, tetracycline, ciprofloxacin, spectinomycin
      and ceftriaxone was determined using the agar dilution method. NG strains ATCC
      49226 and WHO G, J, L, and P were used for quality control. Azithromycin
      resistant isolates were defined as having an MIC value equal to or greater than
      that of strain WHO P, which is internationally recognized as azithromycin
      resistant (MIC = 2 mg/L), and genotyped using NG multiantigen sequence typing.
      RESULTS: The MIC values of strain WHO P for azithromycin were 2 to 4 mg/L in all
      runs, which showed that the method provided consistent and reliable MIC values.
      Seventeen isolates (5.3%) showed resistance to azithromycin. Among these isolates
      (n = 17), 11 sequence types (STs) were identified by NG multiantigen sequence
      typing, of which 5 were novel. The most common ST was ST3356, represented by 6
      isolates. ST1866 was represented by 2 isolates, which were isolated from patients
      with an unknown relationship, and both isolates were highly resistant to
      azithromycin, i.e., displayed an MIC of >64 mg/L. CONCLUSIONS: A relatively high
      prevalence of azithromycin-resistant NG strains implies that azithromycin should
      not be recommended for the treatment of gonococcal urethritis or cervicitis in
      China.

PMID- 21844728
TI  - Antimicrobial resistant gonorrhea in Atlanta: 1988-2006.
AB  - Gonococcal isolates (n = 4336) were collected from men with urethritis at the
      Fulton County STD Clinic between 1988 and 2006. Antimicrobial susceptibility was
      performed by agar dilution. Increasing numbers of isolates from men who have sex
      with men and with fluoroquinolone resistance were noted. New antimicrobials
      effective against gonorrhea are urgently needed.

PMID- 21844729
TI  - Screening of oropharynx and anorectum increases prevalence of Chlamydia
      trachomatis and Neisseria gonorrhoeae infection in female STD clinic visitors.
AB  - BACKGROUND: The relevance of screening of oropharynx and anorectum in addition to
      endocervical tests for detection of Chlamydia trachomatis and Neisseria
      gonorrhoeae infection is unclear in women, while there is a documented benefit of
      this approach in men who have sex with men. METHODS: Female visitors to the
      sexually transmitted disease (STD) clinic were asked about their sexual practice
      as a part of the routine electronic patient file. In addition to tests for
      endocervical infection, swabs were taken from the oropharynx and anorectum to
      test for C. trachomatis and N. gonorrhoeae based on the history of sexual
      contact. Routinely, all electronic patient files are anonymously included in a
      database for surveillance purposes. In this observational study, we analyzed all
      consultations in the database over an 18 months period. RESULTS: A total of 4299
      consultations were registered; 10% of women had endocervical chlamydia and 1.1%
      had gonorrhea. The detection rates for C. trachomatis and N. gonorrhoeae from
      oropharyngeal samples were 1.9% and 0.8%, and from anorectal samples 8.7% and
      1.7%, respectively. Except for 2 cases of pharyngeal gonorrhea, all oropharyngeal
      and anorectal infections were asymptomatic. Inclusion of oropharyngeal and
      anorectal tests in the screening protocol was associated with a percentage
      increase in prevalence of chlamydia by 9.5% and gonorrhea by 31%, relative to
      tests for endocervical tests alone. The percentage increase in prevalence was
      higher than that for the symptom-based approach (3.7% and 10.4%, respectively).
      CONCLUSIONS: Inclusion of oropharyngeal and anorectal tests in the STD screening
      protocol increases the prevalence of chlamydia and gonorrhea in women. Screening
      of anatomical sites based on sexual history is preferred over a symptom-based
      protocol.

PMID- 21844730
TI  - A simple new method to triangulate self-reported risk behavior data--the bean
      method.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)/sexually transmitted disease (STD)
      related interventions rely on self-reported risk behavioral data, which are
      biased toward social desirability. It is warranted to develop methods for data
      triangulation. METHODS: Some questions on HIV/STD-related behaviors that were
      asked in 5 face-to-face (FTF) surveys were repeated at the end of the surveys,
      using the newly developed bean method (BM), which requested participants to
      transfer a bean of a particular color from a large jar to a smaller one,
      depending on whether the answer was affirmative (yellow, white, green, or red) or
      not (black); both jars contained 500 mixed-up colored beans. At the end of each
      day, the number of beans for each color was counted and was compared with the
      results of the FTF interviews. Participants were ensured that the researchers
      would not trace their responses. RESULTS: Among female sex workers who were
      noninjecting drug users, the BM as compared with the FTF interviews, reported
      higher prevalence of inconsistent condom use in the last 6 months, unprotected
      sex with the last client, and STD in the last 6 months. Among men who have sex
      with men in Hong Kong, the BM as compared to the FTF interviews, reported higher
      prevalence of unprotected sex with another man and having >3 sex partners in the
      last 12 months. No statistically significant between-method differences were
      reported among injecting drug users. CONCLUSIONS: Results of HIV/STD-related
      behaviors are dependent on mode of data collection. The simple BM can be used
      regularly to triangulate self-reported HIV-related behavioral data obtained from
      FTF interviews.

PMID- 21844731
TI  - Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae among asymptomatic
      women attending the Capital Health region clinics in Kuwait.
AB  - BACKGROUND: Data on the prevalence of Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) infections are not available in Kuwait. This study was conducted
      to determine the prevalence of CT and NG in asymptomatic women attending 4
      primary health care clinics in the Capital Health region. METHODS: A total of
      9239 married women who attended the primary health care centers were offered
      screening tests for CT and NG over a period of 5 years. Of these, 8539 (92.4%)
      accepted participation. Low-vaginal secretions were collected and investigated
      using a molecular strand displacement amplification method. Biodata of all
      participating women were carefully recorded including age, parity, and
      nationality. Unmarried women were excluded since nonmarital sex in Kuwait is
      illegal. RESULTS: Of the 8539 women screened, 69.5% were Kuwaitis while 30.5%
      were non-Kuwaitis. About 51.3% were aged <=40 years. The overall prevalence of CT
      and NG was 2.1% and 1.5%, respectively. The prevalence rates of CT and NG in
      Kuwaitis versus non-Kuwaitis were 1.9% and 2.3% and 1.4% and 1.6%, respectively.
      Both CT and NG were detected more in younger than older women; 1.6% versus 0.5%
      (<=40 years) and 1.2% versus 0.3% (>40 years), respectively. Higher prevalence of
      both infections was recorded in women in monogamous than polygamous marriages and
      in illiterate than educated women. CONCLUSIONS: The prevalence of CT and NG among
      asymptomatic women in Kuwait is low compared with rates from other Gulf
      Cooperation Council countries. Consequently, screening of asymptomatic women is
      not cost effective and is questionable.

PMID- 21844732
TI  - Congenital syphilis, a reemergent disease in Mexico: its epidemiology during the
      last 2 decades.
AB  - OBJECTIVE: To describe the epidemiologic profile of congenital syphilis in Mexico
      between 1990 and 2009. METHODS: The database of the General Direction of
      Epidemiology at the Ministry of Health in Mexico about congenital syphilis was
      reviewed. Data corresponding to the period between 1990 and 2009 were analyzed in
      every state of the Mexican republic. RESULTS: A total of 1717 cases of congenital
      syphilis were reported during the study period. A 16.6% increase was observed
      between 2005 and 2009 and the quinquennium between 2000 and 2004. A trend toward
      increase in the incidence of congenital syphilis was observed with 2.9 new cases
      for each 100,000 babies born alive. The states that displayed significant
      positive trends were as follows: Baja California, Colima, Chihuahua, Jalisco,
      Nayarit, Sinaloa, and Zacatecas. CONCLUSIONS: An increase in the number of cases
      of congenital syphilis is observed; the northern states are the ones that
      contribute the most to the statistics. There is a real need to refine the
      epidemiologic operations to detect and treat the cases of maternal and congenital
      syphilis in the country.

PMID- 21844733
TI  - Evaluation of patients' preferences for genital herpes treatment.
AB  - BACKGROUND: Genital herpes (GH) is widespread, and detrimental to patients'
      quality of life. It is not always adequately treated, however, with potential
      consequences for patients' well-being and healthcare costs. Involving patients in
      treatment decisions can increase their satisfaction and adherence. We
      investigated patients' preferences for different GH treatments. METHODS: A
      discrete choice experiment was administered to 154 subjects with GH. Subjects
      chose between different treatment options: episodic, suppressive, or no
      treatment, described according to: chance of GH recurrence; chance of
      transmitting the GH virus to a partner; chance of becoming infected with HIV;
      number of tablets to be taken every day and during an outbreak; and out-of-pocket
      cost. Subjects' willingness to pay and probability of treatment uptake were
      estimated. RESULTS: Subjects preferred antiviral treatment to no treatment, and
      subjects receiving suppressive treatment preferred this treatment to no
      treatment. Effect of treatment on GH recurrence and HIV infection rates was a
      significant influence on subject's choice, as were the number of tablets taken
      daily and during an outbreak and out-of pocket treatment cost. Subjects were
      willing to pay between $15.50 and $73.41 for treatment. Subjects' willingness to
      pay depends on the type of treatment and their current treatment. CONCLUSIONS:
      Subjects' preferences are influenced by both the treatment they follow and
      attributes of treatment including cost. Knowledge of patients' preferences,
      together with their clinical status, could help decision-makers to optimize
      therapy uptake and success.

PMID- 21844734
TI  - Knowing a sexual partner is HIV-1-uninfected is associated with higher condom use
      among HIV-1-infected adults in Kenya.
AB  - The relation between awareness of sexual partner's HIV serostatus and unprotected
      sex was examined in HIV clinic enrollees. Increased condom use was associated
      with knowing that a partner was HIV-negative (adjusted odds ratio = 5.99; P <
      0.001) versus not knowing partner's status. Partner testing may increase condom
      use in discordant couples.

PMID- 21844735
TI  - Identification of sexual networks through molecular typing of quinolone-resistant
      Neisseria gonorrhoeae in Ontario, Canada.
AB  - Neisseria gonorrhoeae multi-antigen sequence typing technique demonstrated
      multiple sexual transmission networks in Ontario, Canada. Isolates with novel
      sequences had higher odds of originating in Toronto but had no association with
      heightened population-level quinolone exposure. Neisseria gonorrhoeae multi
      antigen sequence typing technique can be a useful tool for investigation of
      multidrug-resistant N. gonorrhoeae emergence in North America.

PMID- 21844736
TI  - Cost-effectiveness analysis of Chlamydia trachomatis screening via internet-based
      self-collected swabs compared with clinic-based sample collection.
AB  - BACKGROUND: Although the Centers for Disease Control and Prevention have
      recommended population-wide Chlamydia trachomatis screening of sexually active
      women less than 26 years of age, more than half of sexually active young women
      are not routinely screened. A Website (IWTK, www.iwantthekit.org), was developed
      in 2004 to promote home-based sample collection. METHODS: A decision tree was
      designed to model a hypothetical cohort of 10,000 women per year who order an
      internet-based C. trachomatis screening kit. We compared the incremental cost
      effectiveness of 2 screening strategies: self-sampling via the IWTK website, and
      traditional, clinic-based screening by the same cohort of women who used IWTK.
      Probabilities and costs were estimated for each node in the decision tree.
      Estimates were derived from primary data, published data, and unpublished health
      data. RESULTS: The internet-based screening strategy prevented 35.5 more cases of
      pelvic inflammatory disease and saved an additional $41,000 in direct medical
      costs as compared with the clinic-based screening strategy. CONCLUSION: Our model
      estimates demonstrated that an internet-based, self-swab screening strategy was
      cost-effective compared with the traditional, clinic-based screening strategy.
      Assuming that the popularity of the use of the internet as a resource for
      information about healthcare and sexually transmitted infections leads to an
      increased use of IWTK, the public health benefit of this cost-effective strategy
      will be even greater.

PMID- 21844737
TI  - Partner notification of sexually transmitted diseases: practices and preferences.
AB  - BACKGROUND: Timely notification and treatment of sex partners exposed to a
      sexually transmitted disease (STD) is essential to reduce reinfection and
      transmission. Our objectives were to determine factors associated with patient
      initiated notification of sex partners and preferences regarding standard partner
      referral versus expedited partner therapy (EPT). METHODS: Participants diagnosed
      with gonorrhea, chlamydia, trichomoniasis, or nongonococcal urethritis within the
      previous year were administered a baseline survey asking about demographics,
      sexual history, and partner treatment preferences (standard partner referral vs.
      EPT). They identified up to 4 sex partners within the past 2 months, and answered
      questions on relationship characteristics, quality, and notification self
      efficacy. At follow-up, participants with a current STD were asked whether they
      notified their partners. Generalized estimating equations were used to evaluate
      the associations between predictor variables and partner notification. RESULTS:
      Of the 201 subjects enrolled, 157 had a current STD diagnosis, and 289 sex
      partners were identified. The rate of successful partner notification was 77.3%
      (157/203 sex partners). Partner notification was increased if the subject had a
      long-term relationship with a sex partner (odds ratio: 3.07; 95% confidence
      interval: 1.43, 6.58), considered the partner to be a main partner (odds ratio:
      2.53; 95% confidence interval: 1.43, 6.58), or had increased notification self
      efficacy. Overall, participants did not prefer EPT over standard referral;
      however, females, those with higher education levels, and those with a prior STD
      preferred EPT. CONCLUSIONS: Patient-initiated partner referral is more successful
      in patients with increased self-efficacy who have stronger interpersonal
      relationships with their sex partners.

PMID- 21844738
TI  - Trichomonas vaginalis infection in women who submit self-obtained vaginal samples
      after internet recruitment.
AB  - BACKGROUND: Submission of self-obtained vaginal samples (SOVs) collected at home
      could remove barriers that women face in getting tested for sexually transmitted
      infections (STIs). Internet recruitment of SOVs is highly acceptable. METHODS:
      Sexually active women >=14 years were recruited by an educational Internet
      program, available at: www.iwantthekit.org (IWTK), which offered free testing for
      trichomonas as part of a panel, which also offered testing for chlamydia and
      gonorrhea. Kits were ordered online, SOVs were sent through US mail to the
      laboratory, and tested by nucleic acid amplification tests. Demographics and
      sexual risk factors were accessed by questionnaires. Women called or were
      contacted to receive their results. RESULTS: Of women requesting kits, 1525 (43%)
      returned swabs by mail. In all, 61% were <25 years, 52% were black, and 80% were
      single. Vaginal discharge was reported by 44%, prevalence for trichomonas was 10%
      (10% for chlamydia, 1% for gonorrhea), and 18% had at least one prevalent STI.
      Multivariate logistic regression demonstrated several significantly associated
      risks factors as follows: adjusted odds ratio for black race was 2.69; for
      residence of Illinois, 3.85; for not having health insurance, 1.57; for lack of a
      bachelor's degree, 5.53; for having 2 to 15 partners, 1.60; for having >=16
      partners in previous year, 3.51; for being bisexual, 2.0; for not always using
      condoms, 3.04; and for having a partner who had a previous STI, 1.71. Age was not
      associated with trichomonas infection. All infected women were treated.
      CONCLUSIONS: A high prevalence of trichomonas and high sexual risk factors were
      demonstrated. Internet recruitment was a useful method of screening women for
      trichomonas infection.

PMID- 21844739
TI  - Clinician and patient recognition of anogenital herpes disease in HIV positive
      men who have sex with men.
AB  - Anogenital ulcers caused by herpes simplex virus type 2 (HSV-2) are associated
      with an increased risk of human immunodeficiency virus (HIV) transmission. When
      compared with clinician examination, HIV/HSV-2 coinfected men who have sex with
      men are frequently unaware of anogenital ulcers. These data highlight the
      importance of condom use and the need for new HSV-2 prevention strategies.

PMID- 21844740
TI  - Factors associated with herpes simplex virus type 2 incidence in a cohort of
      human immunodeficiency virus type 1-seronegative Kenyan men and women reporting
      high-risk sexual behavior.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) is an important cause of genital
      ulcers and can increase the risk for human immunodeficiency virus type 1 (HIV-1)
      transmission. Our objective was to determine the incidence and correlates of HSV
      2 infection in HIV-1-seronegative Kenyan men reporting high-risk sexual behavior,
      compared with high-risk HIV-1-seronegative women in the same community. METHODS:
      Cohort participants were screened for prevalent HIV-1 infection. HIV-1-uninfected
      participants had regularly scheduled follow-up visits, with HIV counseling and
      testing and collection of demographic and behavioral data. Archived blood samples
      were tested for HSV-2. RESULTS: HSV-2 prevalence was 22.0% in men and 50.8% in
      women (P < 0.001). HSV-2 incidence in men was 9.0 per 100 person-years, and was
      associated with incident HIV-1 infection (adjusted incidence rate ratio [aIRR],
      3.9; 95% confidence interval [CI], 1.3-12.4). Use of soap for genital washing was
      protective (aIRR, 0.3; 95% CI, 0.1-0.8). Receptive anal intercourse had a
      borderline association with HSV-2 acquisition in men (aIRR, 2.0; 95% CI, 1.0-4.1;
      P = 0.057), and weakened the association with incident HIV-1. Among women, HSV-2
      incidence was 22.1 per 100 person-years (P < 0.001 compared with incidence in
      men), and was associated with incident HIV-1 infection (aIRR, 8.9; 95% CI, 3.6
      21.8) and vaginal washing with soap (aIRR, 1.9; 95% CI, 1.0-3.4). CONCLUSIONS:
      HSV-2 incidence in these men and women is among the highest reported, and is
      associated with HIV-1 acquisition. Although vaginal washing with soap may
      increase HSV-2 risk in women, genital hygiene may be protective in men.

PMID- 21844741
TI  - Human immunodeficiency virus prevalence is increasing among men who have sex with
      men in China: findings from a review and meta-analysis.
AB  - BACKGROUND AND METHOD: Multiple studies reported a fast-spreading human
      immunodeficiency virus (HIV) epidemic among men who have sex with men (MSM) in
      China. This study aimed to estimate the magnitude and time trends of HIV
      prevalence among MSM in different geographical regions of China through a
      systemic review and meta-analysis. RESULTS: A total of 94 articles were
      identified (25 in English and 69 in Chinese) and analyzed. National HIV
      prevalence among Chinese MSM has increased over this period, from 1.4% (95%
      confidence interval [CI]: 0.8%-2.4%) in 2001 to 5.3% (95% CI: 4.8%-5.8%) in 2009.
      MSM in Southwest China have the highest HIV prevalence, of 11.4% (95% CI: 9.6%
      13.5%) in comparison with other regions, which range 3.5% to 4.8%. CONCLUSION:
      Significant increases in HIV prevalence among MSM were consistently observed
      across all Chinese regions. There is an urgent need for implementation of
      effective public health interventions to curb the spread of HIV infection among
      MSM across China, especially in the Southwest.

PMID- 21844742
TI  - Human immunodeficiency virus testing behaviors among US adults: the roles of
      individual factors, legislative status, and public health resources.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommended an "opt
      out" human immunodeficiency virus (HIV) testing strategy in 2006 for all persons
      aged 13 to 64 years at healthcare settings. We conducted this study to identify
      individual, health, and policy factors that may be associated with HIV testing in
      US adults. METHODS: The 2008 Behavioral Risk Factors Surveillance System data
      were utilized. Individuals' residency states were classified into 4 categories
      based on the legislation status to HIV testing laws in 2007 and HIV/acquired
      immune deficiency syndrome morbidity. A multivariate logistic regression
      adjusting for survey designs was performed to examine factors associated with HIV
      testing. RESULTS: A total of 281,826 adults aged 18 to 64 years answered HIV
      testing questions in 2008. The proportions of US adults who had ever been tested
      for HIV increased from 35.9% in 2006 to 39.9% in 2008. HIV testing varied across
      the individual's characteristics including sociodemographics, access to regular
      health care, and risk for HIV infection. Compared with residents of "high
      morbidity-opt out" states, those living in "high morbidity-opt in" states with
      legislative restrictions for HIV testing had a slightly lower odds of being
      tested for HIV (adjusted odds ratio = 0.96; 95% confidence interval = 0.92,
      1.01). Adults living in "low morbidity" states were significantly less likely to
      be tested for HIV, regardless of legislative status. CONCLUSIONS: To implement
      routine HIV testing in the general population, the role of public health
      resources should be emphasized and legislative barriers should be further
      reduced. Strategies need to be developed to reach people who do not have regular
      access to health care.

PMID- 21844743
TI  - Health care seeking among men with genital ulcer disease in South Africa:
      correlates and relationship to human immunodeficiency virus-1 and herpes simplex
      virus type 2 detection and shedding.
AB  - BACKGROUND: Episodic acyclovir therapy has been added to genital ulcer disease
      (GUD) syndromic management guidelines in several sub-Saharan African countries
      with human immunodeficiency virus (HIV) epidemics. We examined the correlates of
      health care seeking in men with GUD and its relationship to HIV-1 and herpes
      simplex virus type 2 outcomes. METHODS: Men with GUD (n = 615) were recruited
      from primary health care clinics in Gauteng province, South Africa for a
      randomized controlled trial of episodic acyclovir therapy. We used baseline
      survey and sexually transmitted infection/HIV-testing data to examine delay in
      health care seeking (defined as time from ulcer recognition to baseline study
      visit). RESULTS: Median delay in health care seeking for GUD was 5 days, and one
      quarter of men had previously sought care for the current ulcer. Previous care
      seekers were older, had more episodes of ulceration in the past year, and were
      more likely to test seropositive for HIV-1 and HSV-2. Delay in health care
      seeking was significantly associated with age, education level, and sex during
      the ulceration episode. Delays in care seeking were related to poorer HIV-1
      outcomes; these findings were valid after controlling for advanced HIV.
      CONCLUSIONS: Interventions to help shorten the duration between ulcer recognition
      and health care seeking for men with GUD are needed.

PMID- 21844744
TI  - Antibiotic-resistant phenotypes and genotypes of Neisseria gonorrhoeae isolates
      in Japan: identification of strain clusters with multidrug-resistant phenotypes.
AB  - OBJECTIVES: To determine the antibiotic susceptibility and the genotype
      distributions of N. gonorrhoeae isolates in Fukuoka, Japan, and to evaluate the
      specific associations between genotypes and antibiotic resistance. METHODS:
      Antibiotic susceptibility testing and N. gonorrhoeae multiantigen sequence typing
      (NG-MAST) were performed on 242 and 239 N. gonorrhoeae isolates, respectively, in
      Fukuoka, Japan in 2008. RESULTS: No isolates showed resistance to spectinomycin,
      ceftriaxone, or cefixime, although 34 (14.0%) and 149 (61.6%) isolates displayed
      decreased susceptibility to ceftriaxone (minimum inhibitory concentration range,
      0.06-0.5 mg/L) and cefixime (minimum inhibitory concentration range, 0.06-0.5
      mg/L), respectively. Furthermore, 171 (70.7%), 68 (28.1%), 39 (16.1%), and 1
      (0.4%) isolates were resistant to ciprofloxacin, tetracycline, penicillin, and
      azithromycin, respectively. The 239 isolates were divided by NG-MAST into 67
      sequence types (STs); the 4 most common STs were ST2958 (20.5%), ST4018 (7.5%),
      ST1407 (6.7%), and ST4487 (5.9%). ST2958 and ST1407 were characterized by a
      multidrug-resistant phenotype, whereas ST4018 and ST4487 presented a susceptible
      phenotype. Interestingly, ST1407, which is now common in Europe and Australia,
      was identified as a predominant ST in this study. CONCLUSIONS: This is the first
      report combining N. gonorrhoeae antibiotic susceptibility testing with molecular
      typing by using NG-MAST in Japan. Although a large diversity in NG-MAST was
      identified, based on comparisons with the international data, the ST1407 with a
      multidrug-resistant phenotype currently seems to be circulating worldwide.

PMID- 21844745
TI  - Cytomegalovirus proctitis: a rare and disregarded sexually transmitted disease.
AB  - A review of published cases and a recently managed patient is presented, which
      describes the clinical features of cytomegalovirus proctitis. About half of the
      reports describe sexually transmitted cytomegalovirus proctitis following anal
      intercourse, which typically presents with rectal bleeding and a mononucleosis
      like syndrome. This condition resolves spontaneously and may be associated with
      human immunodeficiency virus infection.

PMID- 21844746
TI  - Recurrent PID, subsequent STI, and reproductive health outcomes: findings from
      the PID evaluation and clinical health (PEACH) study.
AB  - PEACH trial data were used to evaluate the relationship between subsequent
      sexually transmitted infection and recurrent pelvic inflammatory disease on
      infertility and chronic pelvic pain (CPP). Recurrent pelvic inflammatory disease
      was associated with an almost 2-fold increase in infertility and more than 4-fold
      increase in CPP. Subsequent sexually transmitted infection was associated with
      CPP, but not infertility.

PMID- 21844748
TI  - Outcomes of HIV partner services for people with HIV and STD coinfection versus
      new HIV diagnosis: implications for HIV prevention strategies.

PMID- 21844747
TI  - Bacterial vaginosis and risk for Trichomonas vaginalis infection: a longitudinal
      analysis.
AB  - BACKGROUND: Bacterial vaginosis (BV) and Trichomonas vaginalis (TV) have been
      estimated to affect one-quarter to one-third of sexually active women worldwide,
      and are often found concurrently. Few studies have examined this relationship
      longitudinally to better understand the direction and temporality of this
      association. METHODS: Between 2005 and 2006, a cohort of 853 young, sexually
      active women was followed in Mysore, India; participants were interviewed and
      tested for BV and TV at baseline, and at 3- and 6-month visit. Generalized
      estimating equations were used to estimate how changes in vaginal flora between
      consecutive visits-as defined by Nugent diagnostic criteria for BV-were related
      to the risk of TV infection at the latter visit, adjusted for sociodemographic
      and behavioral covariates. Treatment was offered to women with TV and/or
      symptomatic BV. RESULTS: After adjustment for covariates, participants with
      abnormal vaginal flora at 2 consecutive visits had 9 times higher risk of TV (95%
      CI: 4.1, 20.0) at the latter visit, relative to those with persistently normal
      flora. An increased risk of TV was also observed for participants whose flora
      status changed from normal to abnormal (adjusted risk ratio: 7.11, 95% CI: 2.8,
      18.2) and from abnormal to normal (adjusted risk ratio: 4.50, 95% CI: 1.7, 11.8).
      CONCLUSIONS: Women experiencing abnormal flora during a 3-month span appear to
      have significantly increased risk of acquiring TV infection. Women of
      reproductive age in low-resource settings found to have abnormal vaginal flora
      should be assessed for TV.

PMID- 21844749
TI  - Ending a failed intervention: STD performance measures.

PMID- 21844750
TI  - Clinical applications of submucosal endoscopy.
AB  - PURPOSE OF REVIEW: Submucosal endoscopy with mucosal flap (SEMF), a new
      diagnostic and therapeutic intervention of flexible endoscopy, has been examined
      from the perspective of developmental laboratory work, procedural details, and
      results of early clinical experiences. RECENT FINDINGS: Diagnostic natural
      orifice translumenal endoscopic surgery (NOTES) procedures, endolumenal achalasia
      myotomy, and submucosal tumor excision have been clinically performed with a SEMF
      method. The outcomes of these procedures were equivalent to standard surgery but
      with reduced morbidity. Some were accomplished under conscious sedation within
      the endoscopy unit. SUMMARY: The SEMF procedure was originally developed to
      provide safe access to the peritoneal cavity for NOTES procedures. In the SEMF
      method, the submucosal layer is endoscopically tunneled and the resultant space
      is used as an endoscopic path into deeper layers of the gut wall and an offset
      exit to the peritoneal cavity. Key to the method is the overlying mucosa which
      serves as a sealant flap minimizing the risk of soiling a body cavity with
      lumenal contents and the ease by which the entry point into the submucosal
      working space can be closed. Positive outcomes of the early SEMF clinical
      experiences validate that the submucosa can be transformed into a promising novel
      working space for flexible endoscopy.

PMID- 21844751
TI  - Beyond conventional endoscopic ultrasound: elastography, contrast enhancement and
      hybrid techniques.
AB  - PURPOSE OF REVIEW: Endoscopic ultrasound (EUS) recently became a technique with a
      major clinical impact in digestive diseases. EUS determines a change in the
      diagnosis and management of more than half of examined patients. This review
      summarizes recent advances in the complementary EUS examination modalities such
      as elastography and microbubble contrast enhancement. RECENT FINDINGS: EUS
      elastography is a well documented method that allows characterization and
      differentiation of pancreatic cancer and chronic pancreatitis. Quantitative
      elastography methods, especially based on computer analyses, retrieve numeric
      values and possibly eliminate the human bias. The use of contrast-enhanced EUS
      also allows a better visualization and differentiation of focal pancreatic
      lesions. A hypoenhanced mass as compared with the surrounding pancreatic
      parenchyma is highly suggestive for pancreatic adenocarcinoma, whereas a
      hyperenhanced lesion indicates an inflammatory mass. Furthermore, hybrid EUS
      imaging techniques (in combination with computed tomography or magnetic
      resonance) might be useful for an increased diagnostic confidence. SUMMARY:
      Despite its advantages in assessing the organs situated near the gastrointestinal
      tract, EUS is still an operator-dependent technique. The new EUS examination
      modalities incorporated in modern ultrasound systems allow a highly accurate
      diagnosis.

PMID- 21844752
TI  - Molecular mechanisms of pancreatic injury.
AB  - PURPOSE OF REVIEW: Despite being a subject of much scientific scrutiny, the
      pathogenesis of acute pancreatitis is still not well understood. This article
      reviews recent advances in our understanding of acute pancreatitis. RECENT
      FINDINGS: Zymogen activation, observed within acini early during acute
      pancreatitis for a long time, was shown to be sufficient to induce acute
      pancreatitis. Another key early event, NFkappaB activation, has previously been
      shown to induce acute pancreatitis. The relationship between these two key early
      steps is beginning to be clarified. Mechanisms of zymogen activation - pathologic
      calcium signaling, pH changes, colocalization and autophagy, and of NFkappaB
      activation have been investigated intensively along with potential therapeutic
      targets both upstream and downstream of these key events. Additional key findings
      have been elucidation of the role of bioenergetics and the dual role of oxidative
      stress in acute pancreatitis, recognition of endoplasmic reticulum stress as an
      early step and the status of duct cells as important entities in pancreatic
      injury. SUMMARY: Current findings have provided further insight into the roles
      and mechanisms of zymogen activation and inflammatory pathways in pancreatic
      injury. Future studies, which will be of great importance in identifying
      therapeutic targets, are being undertaken to establish the relative contributions
      of these pathways during acute pancreatitis.

PMID- 21844753
TI  - Chronic pancreatitis.
AB  - PURPOSE OF REVIEW: We review important new clinical observations in chronic
      pancreatitis made in the past year. RECENT FINDINGS: Tropical pancreatitis
      associates with SPINK1 and/or CFTR gene mutations in approximately 50% of
      patients, similar to the frequency in idiopathic chronic pancreatitis.
      Corticosteroids increase secretin-stimulated pancreatic bicarbonate
      concentrations in autoimmune pancreatitis (AIP) by restoring mislocalized CFTR
      protein to the apical ductal membrane. Most patients with asymptomatic
      hyperenzymemia have pancreatic lesions of unclear significance or no pancreatic
      lesions. Common pitfalls in the use of diagnostic tests for exocrine pancreatic
      insufficiency (EPI) confound interpretation of findings in irritable bowel
      syndrome and severe renal insufficiency. Further study is needed to improve the
      accuracy of endoscopic ultrasonography (EUS) to diagnose chronic pancreatitis.
      Celiac plexus block provides short-term pain relief in a subset of patients.
      SUMMARY: Results of this year's investigations further elucidated the genetic
      associations of tropical pancreatitis, a reversible mislocalization of ductal
      CFTR in AIP, the association of asymptomatic pancreatic hyperenzymemia with
      pancreatic disorders, limitations of diagnostic tests for EPI, diagnosis of
      chronic pancreatitis by EUS and endoscopic pancreatic function testing and
      treatment of pain.

PMID- 21844756
TI  - Current world literature.

PMID- 21844754
TI  - Genetics of pancreatitis.
AB  - PURPOSE OF REVIEW: Chronic pancreatitis is a syndrome characterized by chronic
      inflammation of the pancreas, with variable pain, calcifications, necrosis, fatty
      replacement, fibrosis and scarring and other complications. Disease
      susceptibility, severity, progression and pain patterns vary widely and do not
      necessarily parallel one another. Much of the variability in susceptibility to
      recurrent acute and chronic pancreatitis is now clearly shown to be related to
      genetic differences between patients. This review highlights recent advances and
      future directions in genetic research. RECENT FINDINGS: The strongest risk
      factors are associated with genetic variations in PRSS1, SPINK1, CFTR, and to a
      lesser extent, CTRC and CASR. The latest research suggest that a single factor
      rarely causes pancreatitis, and the majority of patients with recurrent acute and
      chronic pancreatitis have multiple variants in a gene, or epistatic interactions
      between multiple genes, coupled with environmental stressors. SUMMARY: Pancreatic
      diseases have a strong genetic component. Rather than a classic Mendelian
      disorder, recurrent acute and chronic pancreatitis represents truly complex
      diseases with the interaction and synergism of multiple genetic and environmental
      factors. The future will require new predictive models to guide prevention and
      therapy.

PMID- 21844757
TI  - Morbidity pattern of low-birth-weight infants in an urban slum of Kolkata, India.
AB  - BACKGROUND: Low birth weight (birth weight<2500 g) is one of the major
      determinants of neonatal morbidity as well as mortality and these are known to be
      significantly higher in these infants. OBJECTIVE: To study the morbidity pattern
      of low-birth-weight (LBW) infants in an urban slum in Kolkata, India. MATERIALS
      AND METHODS: A follow-up community-based study was undertaken in 2004-2005 in an
      urban slum of Chetla (Kolkata, West Bengal, India), among 126 singleton live-born
      babies, who were followed up for 9 months at 15+/-5 days interval by home visits.
      RESULTS: Incidence of LBW was 28.6%. Morbidity episodes and hospitalization rate
      were more in LBW than in normal-birth-weight infants. Overall, gastrointestinal
      infection and acute respiratory infection were predominant in both LBW and normal
      birth-weight babies. CONCLUSION AND RECOMMENDATIONS: Although morbidity episodes
      as well as hospitalization rate were lower compared with other studied slums of
      India, there is still room for further improvement of health status of these
      babies. Adequate care, exclusive breast-feeding, and proper nutrition of the LBW
      infants must be ensured to have healthy lifestyle free from morbidity.

PMID- 21844758
TI  - Microbial content of Yarmuk River and King Abdulla Canal waterways in Jordan.
AB  - AIM: The aim of this study was to monitor the microbiological contamination of
      the water of Yarmuk River (YR) and King Abdulla Canal (KAC) in Jordan for 6
      months (June-November 2000) for their aerobic plate count, total coliforms, fecal
      coliforms, fecal Streptococci, Staphylococcus aureus, Salmonella, fungi, algae,
      and protozoa. MATERIAL AND METHODS: Water samples were collected monthly for 6
      months (June-November 2000) from three generally representable locations of each
      of YR and KAC. The procedures of Standard Methods for the Examination of Water
      and Waste Water were, in general, used. RESULTS: The average counts in log colony
      forming units/ml water were 5.4, 4.9 aerobic plate counts; 3.4, 3.5 total
      coliforms; 2.0, 1.9 fecal coliforms; 1.7, 1.6 S.aureus; and 1.7, 1.7 fungi (molds
      and yeasts), respectively. The presumptive tests for Salmonellae were positive in
      all samples of the two waterways. Average algae and protozoa counts during 4
      months (July-October) in 5-l water samples as log/liter were 6.7, 6.9 in Yarmuk
      River and 3.2, 3.4 in King Abdulla Canal, respectively. The microbial contents of
      the sediments of the two waterways and temperature, pH, electric conductivity,
      turbidity, and dissolved oxygen were also recorded. CONCLUSION AND
      RECOMMENDATIONS: From the public point of view, the microbial water quality of
      the two waterways is not suitable for drinking before treatment; it is, however,
      suitable for agricultural restricted irrigation.

PMID- 21844759
TI  - Assessment of exposure of Egyptian infants to aflatoxin M1 through breast milk.
AB  - BACKGROUND: Mothers are exposed to many toxins that can reach their infants
      through breast milk. One of these toxins is aflatoxins, produced by Aspergillus
      fungus. Aspergillus colonizes grains, especially in tropical regions where there
      is high temperature and humidity. Aflatoxins are highly toxic, mutagenic,
      teratogenic, and carcinogenic. One of these is aflatoxin B1 that is excreted in
      breast milk as aflatoxin M1 (AFM1). MATERIALS AND METHODS: This is a cross
      sectional study in which 150 mother-infant dyads were included. All the infants
      were exclusively breastfed. Infant weights' standard deviation scores were
      documented at birth and at 6 months. At 6 months, before starting weaning, AFM1
      was measured in breast milk by enzyme-linked immunosorbent assay and by liver
      enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for
      all mothers and infants. RESULTS: Ninety-eight mothers (65.3%) had AFM1-positive
      breast milk samples (AFM1>0.05 MUg/l according to the European Community and
      Codex Alimentarius). AFM1 levels ranged between 0.2 and 19.0 MUg/l (mean: 7.1+/
      5.0 MUg/l). In cases considered negative, AFM1 levels ranged between 0.01and 0.05
      MUg/l (mean: 0.04+/-0.01 MUg/l). Infants of AFM1-positive mothers had lower
      weight standard deviation scores at birth and at 6 months (P=0.04 and 0.0001).
      ALT and aspartate aminotransferase of mothers and ALT of infants were
      significantly higher in dyads having AFM1-positive breast milk (P=0.0001, 0.0001,
      and 0.03, respectively). CONCLUSION: Aflatoxins represent a real threat in Egypt.
      The higher liver enzymes in AFM1-positive cases might represent an alarm toward
      future development of hepatocellular carcinoma. RECOMMENDATIONS: Cooperation of
      ministries is recommended to combat this problem. The public should be educated
      about proper food storage and about the hazards of aflatoxin ingestion.

PMID- 21844760
TI  - Relationship between obesity and other risk factors and skin disease among adult
      Saudi population.
AB  - BACKGROUND: Obesity is accused for a wide spectrum of dermatologic diseases; no
      previous follow-up study has been conducted to investigate these conditions in
      adult male and female Saudi population. OBJECTIVES: To describe obesity pattern
      using BMI and to assess the association between obesity and certain skin diseases
      among adult Saudi population. MATERIALS AND METHODS: A retrospective cohort study
      of 2-year duration was conducted. The study sample was randomly selected from
      dermatology clinics at Qassim. Male cohorts were 61 obese adults and 48 nonobese
      adults. Female cohorts were 32 obese adults and 36 nonobese adults. Measurement
      of BMI, waist-hip ratio, fasting glucose, blood pressure, and dermatological
      examination was performed. RESULTS: Skin disease incidence was significantly
      increased among exposed rather than nonexposed cohorts with a relative risk of
      2.3 in male cohort and 2.3 in female cohort. Acanthosis nigricans and striae
      distensae incidence increased in exposed men and women with highly significant
      difference from nonexposed groups. Skin tag incidence significantly increased in
      the exposed male cohorts only but not the female cohort. Hirsutism, dry skin,
      pruritis, and planter keratosis all showed nonsignificant differences. The most
      frequently reported infections in obese men were tinea pedis (18%), intertrigo
      (14.7%), and bacterial folliculitis (13.1%) with significant difference. BMI was
      the only risk factor that regresses on skin disease occurrence in study groups.
      CONCLUSION AND RECOMMENDATIONS: Our study linked incidence of acanthosis
      nigricans and striae distensae to obesity in both female and male adult
      population but showed sex difference for other skin diseases, which raised many
      questions and requires further longer duration follow-up studies.

PMID- 21844761
TI  - Pediatric cardiomyopathies over the last decade: a retrospective observational
      epidemiology study in a tertiary institute, Egypt.
AB  - BACKGROUND: Pediatric cardiomyopathy (CM) is a rare, life-threatening disorder of
      unknown etiology. Data on CM in Egypt are scarce as there is no national
      registry. This study was an effort to understand the demographic features,
      clinical presentation, and frequency of different types of childhood CM in Egypt.
      MATERIALS AND METHODS: Medical files of all children diagnosed with CM in the
      last decade (1997-2007) and referred to the Pediatric Cardiology Clinic at Ain
      Shams University, Children's Hospital (Cairo, Egypt), were reviewed. This study
      included 124 (6.6%) cardiomyopathic patient files from a total of 1876 cardiac
      patients that were followed up at the Pediatric Cardiology Clinic during the 10
      year study period. RESULTS: In the last decade (1997-2007), children with CM
      represented 6.6% of all children with cardiovascular diseases followed at the
      Pediatric Cardiology Clinic; 73 were boys (58.9%) and 51 were girls (41.1%), with
      a mean age of 3.82+/-3.99 years. Parental consanguinity was positive in 19.4% of
      patients and a history of preceding viral infection was present in one patient
      (0.8%). Eight patients had a similarly affected sibling (6.5%). CONCLUSION AND
      RECOMMENDATIONS: Data on CM in Egypt are scarce, highlighting the urgent need for
      a national registry for CM (a) to allow more accurate assessment of the size of
      this problem, especially in children; (b) to minimize loss of follow-up data when
      patients move from one region to another; and (c) to allow screening of family
      members of a proband case.

PMID- 21844762
TI  - Epidemiology of sleep disorders in patients with chronic renal disease in Cairo,
      Egypt.
AB  - BACKGROUND: Many patients with end-stage renal disease undergoing dialysis
      therapy suffer from sleep disturbances. The aims of this study were to determine
      the prevalence of sleep disorders in patients with end-stage renal disease on
      maintenance dialysis and to determine the risk factors underlying these
      disorders. PATIENTS AND METHODS: A total of 264 patients on maintenance dialysis
      were enrolled in the study. Demographic, renal, and dialysis data were recorded.
      Using Personal Professional Interviews, we assessed the presence of the following
      sleep disorders: insomnia, restless leg syndrome (RLS), and obstructive sleep
      apnea syndrome (OSAS). Moreover, to determine the prevalence of sleep
      disturbances and the possible effect of demographic or clinical data on sleep, we
      divided our population into two groups: with and without sleep disorders.
      RESULTS: The prevalence of sleep disorders was 61.4%. The survey revealed the
      presence of insomnia (57.6%), RLS (56.4%), and OSAS (21.2%). Insomnia, RLS, and
      OSAS were significantly associated with inadequate dialysis, hyperphosphatemia,
      and hypoalbuminemia. Insomnia and RLS were also significantly associated with
      anemia. Significant independent association was observed between insomnia and
      both RLS and OSAS as well as between RLS and OSAS. CONCLUSION: The survey showed
      a high prevalence of sleep disruption in dialytic populations. Our data might
      help nephrologists to deal with patients with uremia with possible sleep
      disorders.

PMID- 21844763
TI  - Factors associated with cesarean deliveries at Women Specialized Hospital Riyadh,
      King Fahd Medical City, Kingdom of Saudi Arabia.
AB  - BACKGROUND: The risks and safety of cesarean section (CS) differ from place to
      place in the world. According to the World Health Organization, the best outcomes
      for mothers and babies appear to occur with CS rates of 5-15%. Increasing
      maternal age and high parity are among the chief determinants of cesarean
      deliveries. MATERIALS AND METHODS: A retrospective cohort study was done at the
      tertiary care facility, King Fahd Medical City, Riyadh from 1 January to 31
      December 2008. Observations were recorded from the labor ward registers. Sample
      size estimated was n=2192. A total of 2907 patients were recruited. All CS at
      viable gestation were included. Vaginal deliveries were taken as the comparison
      group. Non probability convenient sampling was done. Factors associated with
      cesarean deliveries were analyzed using univariate and bivariate analysis
      methods. Level of significance was set at P<=0.05 and confidence interval
      (CI)=95% respectively. RESULTS: Independent sample t test and Pearson's chi
      square test showed that increasing maternal age, parity (P=0.0001 and 0.002
      respectively), and prematurity (P=0.0001) were significant associates for CS.
      Binary logistic regression also confirmed significant association of increasing
      parity and prematurity (P=0.02 and 0.0001 respectively). Non-reassuring
      cardiotocography was the most common indication for CS. CONCLUSION AND
      RECOMMENDATIONS: Increasing maternal age and parity as well as prematurity were
      the factors significantly associated with CS. Fetomaternal outcome was comparable
      between vaginal and abdominal deliveries, despite the high CS rate. Non
      reassuring cardiotocography was the most common indication. Secondary tests for
      evaluation of fetal well being might help to reduce the high CS rate.

PMID- 21844764
TI  - Letters.

PMID- 21844765
TI  - I am a nurse.

PMID- 21844767
TI  - Taking code blue education to the units.

PMID- 21844770
TI  - Exploring perceptions of nursing image in an inner-city hospital.

PMID- 21844773
TI  - Chronic obstructive pulmonary disease.

PMID- 21844774
TI  - Surviving posttraumatic stress disorder.

PMID- 21844775
TI  - Take a cool look at therapeutic hypothermia.

PMID- 21844777
TI  - Taking a novice nurse under your wing.

PMID- 21844778
TI  - Growing up a nurse.

PMID- 21844779
TI  - Take precautions with audible alarms on ventilators.

PMID- 21844780
TI  - Stoplight system for pressure ulcer risk assessment.

PMID- 21844782
TI  - Spinal epidural hematoma.

PMID- 21844783
TI  - Magnet resonance imaging safety of the Vibrant Soundbridge system: a review.
AB  - OBJECTIVE: To review the current knowledge on magnetic resonance imaging (MRI)
      safety of the Vibrant Soundbridge (VSB) system, an implantable, active middle ear
      implant. DATA SOURCES: National Library of Medicine's online database and
      clinical reports. STUDY SELECTION: All available articles from 1995 to 2010 on
      MRI compatibility of the VSB and other active middle ear implants. RESULTS: Minor
      demagnetization was found for alignments of the magnets antiparallel to the
      magnetic field of the scanner, which played no clinically important role. In some
      cases, the torque forces upon MRI scanning can lead to pain and/or dislocation of
      the implant or dislocation of the floating mass transducer (FMT) depending on its
      type of positioning and attachment in the middle ear. Consecutive need of
      revision surgery is possible. Voltage induction may cause loud audible sounds;
      however, there were no reports for cochlear hearing loss. No significant heating
      effects upon MRI scanning were reported. Image artifacts occur especially because
      of the large magnet. In none of the patient or temporal bone studies, the
      ossicles, round or oval window, or other middle ear structures were injured, and
      there was no functional loss of the implant performance (i.e., demagnetization of
      the FMT). CONCLUSION: MRI examinations of up to 1.5T may be of crucial diagnostic
      importance to the patients implanted with a VSB, but there seems no serious risk
      of harm to the patient or damage to the VSB. A dislocation of the FMT can be
      possible during MRI, and this does depend on transducer position and the security
      of the transducer to the vibratory structure and the coupling mode used. The next
      generation of VSB systems should consider those possible changes in its design.

PMID- 21844784
TI  - Unilateral vestibular loss due to systemically administered gentamicin.
AB  - OBJECTIVE: To report the little known fact that systemically administered
      gentamicin can cause severe unilateral, rather than only bilateral vestibular
      loss. METHODS: This is a retrospective review of patients presenting with
      imbalance and oscillopsia due to a compensated, selective unilateral vestibular
      loss, who denied ever experiencing vertigo, but who had been administered
      systemic gentamicin during a hospital admission just before their symptoms began.
      RESULTS: From 1993 to 2011, 18 such patients were identified from the records of
      our tertiary referral Balance Disorders Clinic. The fact that they had been
      administered gentamicin was confirmed only when the hospital charts were
      examined. Only 4 of 18 patients knew or suspected that they had been administered
      gentamicin; none had been administered gentamicin at the authors' hospital.
      CONCLUSION: These results mean that any patient presenting with imbalance due to
      a compensated, selective unilateral vestibular loss, who has never experienced
      vertigo, should be closely questioned about any hospital admission just before
      symptoms started and the hospital records for that admission requisitioned and
      scrutinized for possible gentamicin therapy.

PMID- 21844785
TI  - The ossicle of Paaw.
AB  - Some anatomists have reported more than 3 ossicles within the middle ear. The
      most widely discussed of these is the lenticular ossicle, which we now understand
      to be the lenticular process forming the distal tip of the long process of the
      incus. Another supernumerary ossicle, within the stapes tendon, has also been
      described by a number of anatomists. Here, we examine the history of this
      ossicle's discovery, the sources of confusion concerning its existence in humans,
      and its presence in some mammalian species. We also discuss the variability in
      the nomenclature of supernumerary ossicles for historical accounts.

PMID- 21844786
TI  - What's new in Shock, September 2011?

PMID- 21844789
TI  - Adenosine diphosphate receptor antagonist clopidogrel sulfate attenuates LPS
      induced systemic inflammation in a rat model.

PMID- 21844787
TI  - The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via
      alternative activation of macrophages and IL-10 production by B1 cells.
AB  - Localized tissue hypoxia is a feature of infection and inflammation, resulting in
      the upregulation of the transcription factors hypoxia-inducible factor 1alpha and
      nuclear factor kappaB (NF-kappaB) via inhibition of oxygen sensing hydroxylase
      enzymes. Previous studies have demonstrated a beneficial role for the hydroxylase
      inhibitor dimethyloxallyl glycine (DMOG) in inflammatory conditions, including
      experimental colitis, by regulating the activity of hypoxia-inducible factor 1
      and NF-kappaB. We have demonstrated in vivo that pretreatment with DMOG
      attenuates systemic LPS-induced activation of the NF-kappaB pathway. Furthermore,
      mice treated with DMOG had significantly increased survival in LPS-induced shock.
      Conversely, in models of polymicrobial sepsis, DMOG exacerbates disease severity.
      Dimethyloxallyl glycine treatment of mice promotes M2 polarization in macrophages
      within the peritoneal cavity, resulting in the downregulation of proinflammatory
      cytokines such as TNF-alpha. In addition, in vivo DMOG treatment upregulates IL
      10 expression, specifically in the peritoneal B1 cell population. This study
      demonstrates cell type-specific roles for hydroxylase inhibition in vivo and
      provides insight into the mechanism underlying the protection conveyed by DMOG in
      models of endotoxic shock.

PMID- 21844790
TI  - Change in temperature profile may precede fever and be an early indicator of
      sepsis: a case report.

PMID- 21844792
TI  - Blood transfusion: the patient's experience.
AB  - OBJECTIVE: Blood transfusion is a standard treatment for anemia in both
      inpatients and outpatients. Nonetheless, few studies on the therapy have examined
      the patient's perspective. This study therefore sought to identify how well
      patients understand the role of blood transfusion in their treatment and whether
      it causes them discomfort. METHODS: All medically stable adults who had received
      a blood transfusion at an Ohio hospital over a five-week period in 2009 were
      identified; a convenience sample of 21 of those patients participated in
      semistructured interviews lasting 15 to 30 minutes. The researchers recorded and
      transcribed the interviews and performed a thematic analysis. RESULTS: Four
      themes emerged: paternalism and decision making, patients' knowledge, blood
      safety and administration, and the nurse's role. Participants said that because a
      physician decided the transfusion would take place, they didn't understand that
      there were other options for treating their anemia; pretransfusion written
      materials weren't adequate to explain risks and benefits of the procedure; they
      had concerns about the safety of the blood supply; and they valued nurses'
      opinions. CONCLUSIONS: These qualitative findings suggest that clinicians may be
      missing opportunities to improve patients' knowledge of and comfort with blood
      transfusion and that they can better meet patients' needs before, during, and
      after the procedure. Further research is warranted. KEYWORDS: blood transfusion,
      lived experience, patient education, qualitative research.

PMID- 21844793
TI  - Ultrasound-guided injection techniques for the low back and hip joint.
AB  - Ultrasound has become a useful adjunct to many procedures performed in
      rehabilitation medicine. It has the advantages of cost-effectiveness, lack of
      radiation, and readiness of use and the ability to make dynamic examinations
      possible compared with other imaging tools. Through dynamic examinations, needles
      can be guided accurately to the target sites to increase the success rates of
      aspiration and injection procedures. At present, ultrasound-guided caudal
      epidural, sacroiliac joint, piriformis muscle, and hip-joint injections are
      commonly practiced in rehabilitation medicine. Perhaps the only disadvantage of
      ultrasound-guided injection technique is the long learning curve that is required
      for the physiatrists to be well acquainted with the simultaneous manipulation of
      ultrasound transducers, placement of needles, and the correct interpretation of
      musculoskeletal sonographic images. This is the first of two review articles on
      ultrasound-guided injections. This article will review the selected ultrasound
      guided injection techniques that are performed in the low-back and hip-joint
      areas. Sonographic images and schematic illustrations of these ultrasound-guided
      injection techniques will be shown.

PMID- 21844794
TI  - p53 codon 72 polymorphism and coronary artery disease: evidence of association
      with left ventricular ejection fraction.
AB  - INTRODUCTION: Recently, there has been a surge of interest on the possible
      relationship between p53 polymorphism and coronary atherosclerosis. The authors
      have investigated the possible association of p53 codon 72 polymorphism with left
      ventricular ejection fraction (LVEF) in subjects with and without coronary artery
      disease (CAD). METHODS: The authors have studied 198 subjects admitted
      consecutively to Valmontone Hospital for CAD and 129 subjects admitted for
      cardiovascular diseases without CAD. Fifty-nine subjects admitted for CAD to
      Division of Cardiac Surgery of Tor Vergata University were also studied. All
      subjects were from the white population. The p53 polymorphism was evaluated using
      the restriction fragment length polymorphism polymerase chain reaction. RESULTS:
      p53 codon 72 polymorphism is a significant independent predictor of LVEF in
      subjects with CAD but not in subjects with cardiovascular disease without CAD. In
      subjects with CAD, LVEF is significantly lower in subjects carrying the *Pro
      variant than in *Arg/*Arg subjects. This effect is more evident in subjects with
      a positive history of infarction. CONCLUSIONS: Our study points to a significant
      relationship of p53 codon 72 polymorphism with cardiac function in subjects with
      CAD.

PMID- 21844796
TI  - Case scenario: perioperative management of a multigravida at 34-week gestation
      diagnosed with abnormal placentation.

PMID- 21844797
TI  - Critical care and cirrhosis: outcome and benefit.
AB  - PURPOSE OF REVIEW: The incidence of cirrhosis is growing steadily and this cohort
      of patients will present in ever-greater numbers to critical care with acute
      decompensation, usually secondary to an inter-current event or following elective
      surgery. This review examines the evidence for treatment options and outcomes.
      RECENT FINDINGS: Outcome of cirrhotics presenting with end-organ dysfunction is
      steadily improving and their outcomes are not as poor as sometimes suggested.
      Treatment options for variceal bleeding and renal dysfunction are evolving and
      outcomes improving. SUMMARY: Critical care support should be offered to patients
      with cirrhosis and in high-risk variceal bleed patients transhepatic
      portosystemic shunt should be considered.

PMID- 21844798
TI  - Pulmonary hypertension in critical care.
AB  - PURPOSE OF REVIEW: To review the contemporary management of patients with
      pulmonary hypertension in critical care. RECENT FINDINGS: The normal mean
      pulmonary artery pressure (mPAP) at rest is 14+/-3  mmHg and pulmonary
      hypertension is considered when mPAP is greater than or equal to 25  mmHg at
      rest. The classification of pulmonary hypertension has been redefined recently
      and updated in 2009 and could help to guide the management of patients with
      pulmonary hypertension in critical care. The management of pulmonary hypertension
      in ICU is based on expert opinion. Among the diagnostic and monitoring tools
      available, echocardiography provides useful information noninvasively, although
      pulmonary artery catheter must be used in case of complicated situations. Calcium
      sensitizers, a new class of inotrope, have inotropic effects and induce
      dilatation of the pulmonary, systemic, and coronary vasculature and thus could be
      useful in case of right ventricular failure (RVF), particularly in patients with
      acute respiratory distress syndrome (ARDS). By increasing the pulmonary
      vasodilator response to inhaled nitric oxide and preventing the rebound pulmonary
      vasoconstriction which occurs following cessation of nitric oxide breathing,
      selective type 5 isoform of phosphodiesterase inhibitors could be useful in
      critically ill patients. SUMMARY: This article reviews recent and key findings on
      the management of pulmonary hypertension in critically ill patients.

PMID- 21844799
TI  - Critical care outcomes: current and future issues.

PMID- 21844800
TI  - Improving outcomes in the early phases after major trauma.
AB  - PURPOSE OF REVIEW: The scope of this review is to describe what is known about
      injury outcomes and the principles by which they can be improved by acute phase
      interventions. Assessing which outcomes matter to trauma patients is important
      both for the evaluation of existing and novel acute interventions and to assess
      the delivery of care within trauma systems' performance improvement frameworks.
      RECENT FINDINGS: Trauma care is moving away from the straightforward assessment
      of simple endpoints such as mortality or amputation. These have limited
      applicability and may not truly demonstrate the effectiveness of some acute
      interventions. Other intermediate or long-term measures are more patient-centred
      but are harder to measure, collect and interpret. Acute interventions improve
      outcomes through a combination of early definitive care concurrent with
      techniques to maintain homeostasis and preserve cells and tissues. These
      interventions need to be delivered within a regional systems framework. Trauma
      systems improve outcomes by reducing randomness and error from trauma care
      pathways. SUMMARY: Improving outcomes in the acute phase of trauma care requires
      the timely delivery of complex interventions with an organized trauma system.
      Research is needed both in developing novel interventions and in developing and
      validating patient-centred and surrogate outcome tools.

PMID- 21844801
TI  - Attributable mortality of ventilator-associated pneumonia.
AB  - PURPOSE OF REVIEW: To critically discuss the attributable mortality of ventilator
      associated pneumonia (VAP) and potential sources of variation. RECENT FINDINGS:
      The review will cover the available estimates (0-50%). It will also explore the
      source of variation because of definition of VAP (being lower if inaccurate),
      case-mix issues (being lower for trauma patients), the severity of underlying
      illnesses (being maximal when the severity of underlying illness is
      intermediate), and on the characteristics and the severity of the VAP episode.
      Another important source of variation is the use of poorly appropriate
      statistical models (estimates biased by lead time bias and competing events). New
      extensions of survival models which take into account the time dependence of VAP
      occurrence and competing risks allow less biased estimation as compared with
      traditional models. SUMMARY: Attributable mortality of VAP is about 6%. Accurate
      diagnostic methods are key to properly estimating it. Traditional statistical
      models should no longer be used to estimate it. Prevention efforts targeted on
      patients with intermediate severity may result in the most important outcome
      benefits.

PMID- 21844802
TI  - Microsporidiosis: not just in AIDS patients.
AB  - PURPOSE OF REVIEW: Microsporidia have emerged as causes of opportunistic
      infections associated with diarrhea and wasting in AIDS patients. This review
      describes recent reports of microsporidiosis in HIV-infected individuals and the
      growing awareness of microsporidiosis in non-HIV-infected populations. RECENT
      FINDINGS: Microsporidia were only rarely recognized as causes of disease in
      humans until the AIDS pandemic. Implementation of combination antiretroviral
      therapy (cART) to curtail HIV replication and restore immune status drastically
      reduced the occurrence of opportunistic infections, including those due to
      microsporidia, in HIV-infected individuals. In developing countries where cART is
      not always accessible, microsporidiosis continues to be problematic. Improvement
      of diagnostic methods over the previous 25 years led to identification of several
      new species of microsporidia, many of which disseminate from enteric to systemic
      sites of infection and contribute to some unexpected lesions. Among non-HIV
      infected but immune-suppressed individuals, microsporidia have infected organ
      transplant recipients, children, the elderly, and patients with malignant disease
      and diabetes. In otherwise healthy immune-competent HIV seronegative populations,
      self-limiting diarrhea occurred in travelers and as a result of a foodborne
      outbreak associated with contaminated cucumbers. Keratitis due to
      microsporidiosis has become problematic and a recent longitudinal evaluation
      demonstrated that non-HIV-infected individuals seropositive for microsporidia who
      had no clinical signs continued to intermittently shed organisms in feces and
      urine. SUMMARY: Greater awareness and implementation of better diagnostic methods
      are demonstrating that microsporidia contribute to a wide range of clinical
      syndromes in HIV-infected and non-HIV-infected people. As such, microsporidia
      should be considered in differential diagnoses if no other cause can be defined.

PMID- 21844803
TI  - Invasive nontyphoidal Salmonella disease: epidemiology, pathogenesis and
      diagnosis.
AB  - PURPOSE OF REVIEW: This review highlights and discusses important publications
      over the past 12 months providing new insights on invasive nontyphoidal
      Salmonella (iNTS) disease. RECENT FINDINGS: There have been informative new
      estimates of the burden of iNTS in Asia and in high-resource, low-incidence
      settings. Important information has emerged in the last year about the
      relationships between HIV, malaria, iNTS and typhoid fever in adults and children
      in Africa. HIV causes susceptibility to iNTS disease, but has been shown to be
      protective against typhoid fever. Clinical guidelines for presumptive diagnosis
      frequently fail to identify iNTS disease in Africa, and there remains a need for
      improved diagnostic tools. Experimental studies in humans have helped us to
      understand the intracellular pathogenesis of iNTS and to direct the search for
      appropriate protein vaccine targets. SUMMARY: The most important remaining gap in
      our knowledge is probably an understanding of how NTS is transmitted, and the
      nature of the relationship between diarrhoeal disease, carriage and invasive
      disease in Africa, so that diagnostic and prevention tools can be appropriately
      directed.

PMID- 21844804
TI  - New Gram-positive antibiotics:  better than vancomycin?
AB  - PURPOSE OF REVIEW: Despite concerns about vancomycin use in the treatment of
      multidrug-resistant Gram positives, evidence for better therapeutic outcomes with
      alternative antibiotics is lacking. This review focuses on recent advances.
      RECENT FINDINGS: Combination therapy with vancomycin-rifampin, although
      associated with better cure rates, resulted in the emergence of high rates of
      rifampin resistance. Of the newer anti-methicillin-resistant Staphylococcus
      aureus (MRSA) antibiotics, ceftopibrole, ortivancin and dalbavancin require
      further development prior to a further assessment by the United States Food and
      Drug Administration. Ceftaroline, telavancin and daptomycin were associated with
      comparable clinical cure rates compared with vancomycin in the treatment of
      complicated MRSA skin and soft tissue infections. In the treatment of hospital
      acquired pneumonia, both telavancin and linezolid resulted in significantly
      greater clinical cure rates compared with vancomycin. Despite greater clinical
      cure rates, no difference in overall or infection-related mortality was detected.
      Of concern is the appearance of daptomycin and linezolid resistance following
      increased use. Toxicity profiles (especially of linezolid) are comparable to
      vancomycin provided short-duration therapy is prescribed. The first reports of
      daptomycin-induced acute eosinophillic pneumonia were described in 2010. SUMMARY:
      Based on current evidence, greater microbiological and clinical cure rates are
      achieved with alternative agents. However, these differences do not translate
      into mortality benefits compared with vancomycin for the treatment of S. aureus
      infections.

PMID- 21844805
TI  - Defining the causes of diarrhea: novel approaches.
AB  - PURPOSE OF REVIEW: Diarrheal disease causes substantial morbidity and mortality
      worldwide; however, defining the microbiologic causes are challenging due to the
      large number of potential enteropathogens that require testing, insensitivity of
      existing conventional methods, the frequent occurrence of mixed infections, and
      high rates of background carriage in many communities. RECENT FINDINGS: Here we
      review recent detection methods for enteropathogens with a particular focus on
      nucleic acid amplification assays. SUMMARY: Nucleic acid amplification assays
      with high sensitivity and throughput now allow screening for multiple
      enteropathogens in stool samples. Interpretation will be complicated by high
      rates of mixed infections and background carriage in many communities. Therefore,
      new detection techniques, including quantitative methods, will need to be
      utilized in conjunction with the clinical context and careful study design. These
      methods should yield new insights into the causes and epidemiology of diarrhea.

PMID- 21844806
TI  - Gastrointestinal infections and the development of irritable bowel syndrome.
AB  - PURPOSE OF REVIEW: Approximately 10% of the millions of persons with functional
      gastrointestinal disorders (FGDs) including irritable bowel syndrome (IBS) had
      their illness onset following an acute bout of infectious diarrhea and are
      referred to as having postinfectious (PI) FGD or PI-IBS. Recent studies have
      helped to identify the pathogenesis and natural history of these disorders.
      RECENT FINDINGS: Groups of patients with acute diarrhea or dysentery (passage of
      grossly bloody stools) are being followed for development of PI-IBS. Persistent
      mucosal inflammation, air trapping in the gut, and alteration of intestinal
      motility contribute to the disease symptoms in genetically susceptible persons.
      The prognosis of postinfectious forms of IBS is more favorable compared with
      people with idiopathic forms of the disorder. SUMMARY: With full characterization
      of postdiarrhea forms of FGDs, we should be able to define the mechanisms of
      disease early in the course of chronic illness and to better understand the more
      common idiopathic forms of the disease. We are likely to identify specific
      alteration of gut pathophysiology in postinfectious FGDs and to then classify
      them not as a poorly characterized group of functional disorders but as specific
      gastrointestinal disorders.

PMID- 21844807
TI  - Coenzyme Q deficiency in muscle.
AB  - PURPOSE OF REVIEW: Coenzyme Q (CoQ) is a vital component of the mitochondrial
      respiratory chain. A number of patients with CoQ deficiency presented with
      different clinical phenotypes, often affecting skeletal muscle, and responded
      well to CoQ supplementation. We discuss recent advances in this field with
      special attention to muscle involvement. RECENT FINDINGS: The identification of
      genetic defects causing CoQ deficiency has allowed to distinguish primary forms,
      due to mutations in biosynthetic genes, from secondary defects caused either by
      mutations in genes unrelated to CoQ biosynthesis or by nongenetic factors. To
      date, none of the patients with genetically proven primary deficiency presented
      with an exclusively (or prominently) myopathic phenotype. Most patients with
      myopathy were found to harbor other genetic defects (mutations in electron
      transferring-flavoprotein dehydrogenase or mitochondrial DNA). The majority of
      patients with CoQ deficiency still lack a genetic diagnosis. The pathogenesis of
      CoQ deficiency cannot be attributed solely to the bioenergetic defect, suggesting
      that other roles of CoQ, including its antioxidant properties or its role in
      pyrimidine metabolism, may also play crucial roles. SUMMARY: Early recognition of
      CoQ deficiency is essential to institute appropriate and timely treatment, thus
      avoiding irreversible tissue damage.

PMID- 21844808
TI  - Cellular alloresponses for rejection-risk assessment after pediatric
      transplantation.
AB  - PURPOSE OF REVIEW: Current immune monitoring practices detect antidonor
      antibodies and antibody-mediated rejection, and are less suited for the detection
      of acute cellular rejection (ACR), the predominant form of rejection after
      transplantation. We review the use of mixed lymphocyte coculture-based assays
      that measure cellular alloresponses, for measurement of the risk of ACR after
      liver, intestine, and kidney transplantation. RECENT FINDINGS: Flow cytometry
      enables the rapid measurement of cellular alloresponses using dilution of the
      intravital dye carboxyfluorescein succinimidyl ester within 72 h or of
      intracellular CD154 in alloantigen-specific T-cells or B-cells within 16 h. Assay
      output is personalized by expressing donor-induced alloresponse as a fraction of
      the third-party alloresponse for each patient. The resulting parameter called the
      immunoreactivity index indicates increased risk of rejection if donor-response
      exceeds third-party response. The rejection-risk threshold immunoreactivity index
      predicts or associates with ACR of liver, kidney, or intestine allografts with
      sensitivity and specificity of 75% or more. Lifelong assessment is facilitated by
      using 'surrogate' donor stimulators from normal human individuals in lieu of
      actual donor cells, without compromising rejection-risk assessment. SUMMARY:
      Cellular alloresponses can measure the risk of ACR accurately in the clinic, so
      that immunosuppression may be managed safely and more effectively in individual
      patients.

PMID- 21844809
TI  - Steroid avoidance in renal transplantation.
AB  - PURPOSE OF REVIEW: The recent surge in the use of steroid-avoidance protocols for
      pediatric renal transplant recipients has been fueled by the numerous adverse
      side effects of steroids and development of alternatives for successful
      immunosuppression. Steroid-avoidance protocols were first attempted in the adult
      population, and with positive outcomes, pediatrics soon followed. As more
      pediatric patients are placed on steroid-avoidance protocols, we must begin
      answering several important questions such as patient and graft outcome, safety
      profiles of various steroid-avoidance induction protocols, viral complications
      and incidence of transplant lymphoproliferative disease (PTLD), metabolic
      benefits, and the affect of steroid minimization on growth. RECENT FINDINGS:
      Initial results from steroid-avoidance protocols show these protocols are safe
      and effective with improved graft survival, metabolic profiles, and linear growth
      without an increase in viremia or PTLD. SUMMARY: Although initial results are
      promising, there is still a lack of long-term data from large, prospective
      randomized trials, and there is not enough data to determine the optimal steroid
      avoidance protocol for pediatric renal transplant recipients.

PMID- 21844810
TI  - Auditory steady state cortical responses indicate deviant phonemic-rate
      processing in adults with dyslexia.
AB  - OBJECTIVES: Speech intelligibility is strongly influenced by the ability to
      process temporal modulations. It is hypothesized that in dyslexia, deficient
      processing of rapidly changing auditory information underlies a deficient
      development of phonological representations, causing reading and spelling
      problems. Low-frequency modulations between 4 and 20 Hz correspond to the
      processing rate of important phonological segments (syllables and phonemes,
      respectively) in speech and therefore provide a bridge between low-level auditory
      and phonological processing. In the present study, temporal modulation processing
      was investigated by auditory steady state responses (ASSRs) in normal-reading and
      dyslexic adults. DESIGN: Multichannel ASSRs were recorded in normal-reading and
      dyslexic adults in response to speech-weighted noise stimuli amplitude modulated
      at 80, 20, and 4 Hz. The 80 Hz modulation is known to be primarily generated by
      the brainstem, whereas the 20 and 4 Hz modulations are mainly generated in the
      cortex. Furthermore, the 20 and 4 Hz modulations provide an objective auditory
      performance measure related to phonemic- and syllabic-rate processing. In
      addition to neurophysiological measures, psychophysical tests of speech-in-noise
      perception and phonological awareness were assessed. RESULTS: On the basis of
      response strength and phase coherence measures, normal-reading and dyslexic
      participants showed similar processing at the brainstem level. At the cortical
      level of the auditory system, dyslexic subjects demonstrated deviant phonemic
      rate responses compared with normal readers, whereas no group differences were
      found for the syllabic rate. Furthermore, a relationship between phonemic-rate
      ASSRs and psychophysical tests of speech-in-noise perception and phonological
      awareness was obtained. CONCLUSIONS: The results suggest reduced cortical
      processing for phonemic-rate modulations in dyslexic adults, presumably resulting
      in limited integration of temporal information in the dorsal phonological
      pathway.

PMID- 21844812
TI  - Eligibility criteria in private and public coverage policies for BRCA genetic
      testing and genetic counseling.
AB  - PURPOSE: : Coverage policies for genetic services for hereditary cancers are of
      interest because the services influence cancer risk reduction for both persons
      with cancer and their family members. We compared coverage policies for BRCA
      genetic testing and genetic counseling among selected payers in the United States
      to illuminate eligibility criteria variation that may explain differential access
      by insurance type. We compared these policies with policies for breast cancer
      screening with magnetic resonance imaging to consider whether payers apply a
      unique policy approach to genetic services. METHODS: : We conducted a case study
      of large private and public payers selected on number of covered lives. We
      examined coverage policies for BRCA genetic testing, genetic counseling, and
      screening with magnetic resonance imaging and the eligibility criteria for each.
      We compared eligibility criteria against National Comprehensive Cancer Network
      guidelines. RESULTS: : Eligibility criteria for BRCA testing were related to
      personal history and family history of cancer. Although private payers covered
      BRCA testing for persons with and without cancer, the local Medicare carrier in
      our study only covered testing for persons with cancer. In contrast, Arizona's
      Medicaid program did not cover BRCA testing. Few payers had detailed eligibility
      criteria for genetic counseling. Private payers have more detailed coverage
      policies for both genetic services and screening with magnetic resonance imaging
      in comparison with public payers. CONCLUSION: : Despite clinical guidelines
      establishing standards for BRCA testing, we found differences in coverage
      policies particularly between private and public payers. Future research and
      policy discussions can consider how differences in private and public payer
      policies influence access to genetic technologies and health outcomes.

PMID- 21844813
TI  - Geriatric care management: role, need, and benefits.
AB  - Care coordination for the older adult is growing based on increases in aging
      populations, fragmentation in healthcare systems, and the desire by many older
      adults to remain in their homes. Geriatric Care Managers (GCMs) guide older
      adults and families in navigating the complexities of the continuum of care and
      with finding available resources for long-term care planning. This article
      reviews the GCM role, which patients may be appropriate for the service, and
      patient benefits.

PMID- 21844811
TI  - An evidence-based approach to establish the functional and clinical significance
      of copy number variants in intellectual and developmental disabilities.
AB  - PURPOSE: Copy number variants have emerged as a major cause of human disease such
      as autism and intellectual disabilities. Because copy number variants are common
      in normal individuals, determining the functional and clinical significance of
      rare copy number variants in patients remains challenging. The adoption of whole
      genome chromosomal microarray analysis as a first-tier diagnostic test for
      individuals with unexplained developmental disabilities provides a unique
      opportunity to obtain large copy number variant datasets generated through
      routine patient care. METHODS: A consortium of diagnostic laboratories was
      established (the International Standards for Cytogenomic Arrays consortium) to
      share copy number variant and phenotypic data in a central, public database. We
      present the largest copy number variant case-control study to date comprising
      15,749 International Standards for Cytogenomic Arrays cases and 10,118 published
      controls, focusing our initial analysis on recurrent deletions and duplications
      involving 14 copy number variant regions. RESULTS: Compared with controls, 14
      deletions and seven duplications were significantly overrepresented in cases,
      providing a clinical diagnosis as pathogenic. CONCLUSION: Given the rapid
      expansion of clinical chromosomal microarray analysis testing, very large
      datasets will be available to determine the functional significance of
      increasingly rare copy number variants. This data will provide an evidence-based
      guide to clinicians across many disciplines involved in the diagnosis,
      management, and care of these patients and their families.

PMID- 21844814
TI  - Review of ectodermal dysplasia: case report on treatment planning and surgical
      management of oligodontia with implant restorations.
AB  - Dental implants have proven to be a reliable modality for the rehabilitation of
      missing teeth. However, there are limited reports on managing anodontia related
      to ectodermal dysplasia in the scientific literature. The severely reduced bone
      quantity due to the congenital absence of multiple natural teeth is the biggest
      challenge for the surgeon. There are a variety of bone augmentation procedures to
      establish adequate bone quantity, and the surgical planning should be used on an
      individual case basis. This is a report of a 19-year-old male patient affected by
      hypohidrotic ectodermal dysplasia. Oligodontia associated with severe atrophy of
      jaws was the chief complaint for seeking treatment. Based on clinical and
      radiographic examinations, 2 bone augmentation procedures were used to obtain
      sufficient width of alveolus for implant placement by performing an onlay bone
      graft in the maxilla and vertical distraction osteogenesis in the mandible. The
      treatment planning was discussed and informed consent was obtained.

PMID- 21844815
TI  - A randomized comparison study of Aquacel Ag and Glucan II as donor site dressings
      with regard to healing time, cosmesis, infection rate, and patient's perceived
      pain: a pilot study.
AB  - This study was undertaken to compare pain, healing time, infection rate, and
      cosmetic outcome between Aquacel Ag (Convatec) and Glucan II (Brennan Medical) as
      donor site dressings. The authors performed a prospective, randomized, patient
      controlled study. Eligible patients had two donor sites harvested. One site was
      dressed with Aquacel Ag and the other site with Glucan II. Patients were followed
      at set time points for 6 months to determine the rate of epithelialization,
      patient's perceived pain, infection rate, and the cosmetic outcome. A total of 20
      patients were enrolled in the study. All patient data were collected through
      reepithelialization. The average time to wound healing for Aquacel Ag was 12.5 +/
      2.07 days compared with Glucan II 12.7 +/- 1.99 days. Perceived pain scores for
      each donor site were recorded. On postoperative day 5, patients reported
      significantly less pain with the Aquacel Ag site (Aquacel Ag 1.75 vs Glucan II
      2.5, P = .02). Three donor sites showed clinical signs of infection (two Glucan
      II and one Aquacel Ag) prompting culture and dressing removal. There was no
      statistically significant difference in cosmetic outcomes of the donor sites at
      any time point. When comparing Aquacel Ag and Glucan II, our study has determined
      that there is no significant difference with regard to healing time, infection
      rates, and cosmetic outcomes. Both dressings are comparable with regard to ease
      of application and postoperative care.

PMID- 21844816
TI  - Metastatic tumor of the heart: description of a case.
AB  - We present the case of a 67-year-old man with a carcinoma of the lung and a
      metastatic tumor of the heart. The diagnosis was made on the basis of
      echocardiogram. In this patient, the first and unique cardiac symptom was
      irreversible sustained ventricular arrhythmia leading to death.

PMID- 21844817
TI  - Spontaneous coronary artery dissection evaluated by optical coherence tomography.
AB  - A 42-year-old woman underwent coronary angiography for acute coronary syndrome.
      It showed a progressive narrowing from the middle segment of the left anterior
      descending artery. Optical coherence tomography (OCT) confirmed the angiographic
      suspicion of spontaneous coronary dissection. OCT also revealed different
      patterns of subjacent disease, imperceptible to the angiography: areas of
      intramural hematoma with blood stasis, progressive compromise of the true lumen,
      and areas with active flow through the false lumen. It also detected the distal
      guidewire going out from the true to the false lumen, a feature of capital
      importance to lead an eventual coronary intervention.

PMID- 21844821
TI  - Valsartan-induced improvement in insulin sensitivity is not paralleled by changes
      in microvascular function in individuals with impaired glucose metabolism.
AB  - BACKGROUND: Individuals with impaired glucose metabolism (IGM) are at high risk
      of developing type 2 diabetes (T2DM). The renin-angiotensin system (RAS) is
      activated in insulin-resistant states and its inhibition resulted in delayed
      onset of T2DM. The underlying mechanisms may include improvement in microvascular
      structure and function, which may increase glucose and insulin delivery to
      insulin-sensitive tissues. We hypothesized that functional and structural
      capillary density is impaired in insulin-resistant individuals with IGM and that
      treatment with the angiotensin-receptor blocker valsartan (VAL) will improve
      insulin sensitivity and microvascular function. METHODS: In this randomized
      controlled trial, individuals with IGM (n = 48) underwent a hyperinsulinaemic
      euglycaemic clamp to assess insulin sensitivity (M-value) and capillaroscopy to
      examine baseline skin capillary density (BCD), capillary density after arterial
      occlusion (PRH) and capillary density during venous occlusion (VEN) before and
      after 26 weeks of VAL or placebo (PLB). Sixteen BMI-matched individuals with
      normal glucose metabolism (NGM) served as controls. RESULTS: Individuals with IGM
      were more insulin resistant (P < 0.001) and had impaired microvascular function
      compared with those with NGM (all P < 0.01). Univariate associations were found
      for microvascular function (BCD, PRH, VEN) and M-value (all P < 0.005). The
      relations were independent of age, sex and BMI. VAL improved insulin sensitivity
      (P = 0.034) and lowered blood pressure as compared with PLB, whereas
      microvascular function remained unchanged. CONCLUSION: In insulin-resistant
      individuals with IGM, impaired functional and structural capillary density was
      inversely associated with insulin sensitivity. VAL improved insulin sensitivity
      without affecting the functional and structural capillary density, indicating
      that other mechanisms may be stronger determinants in the VAL-mediated insulin
      sensitizing effect.

PMID- 21844822
TI  - Prepubertal angiotensin blockade exerts long-term therapeutic effect through
      sustained ATRAP activation in salt-sensitive hypertensive rats.
AB  - OBJECTIVE: We previously showed that the molecule interacting with Ang II type 1
      receptor (AT1R), ATRAP, promotes AT1R internalization and attenuates AT1R
      mediated pathological responses. In this study we examined whether the regulation
      of renal ATRAP expression is related to the development of salt-induced
      hypertension and renal injury as well as to the beneficial effects of AT1R
      blockade. METHODS AND RESULTS: Dahl Iwai salt-sensitive hypertensive and Dahl
      Iwai salt-resistant rats were divided into six groups for the administration of
      vehicle or olmesartan either continuously from 3 to 16 weeks, or transiently from
      weaning to puberty (3-10 weeks), and fed high salt diet from 6 to 16 weeks. In
      Dahl Iwai salt-sensitive rats, not only continuous, but also prepubertal
      olmesartan treatment improved hypertension at 15 weeks. Renal ATRAP expression
      was suppressed in vehicle-treated Dahl Iwai salt-sensitive rats, concomitant with
      up-regulation of renal oxidative stress, inflammation and fibrosis-related
      markers such as p22phox, TGF-beta, fibronectin, monocyte chemotactic protein-1
      and type 1 collagen. However, prepubertal as well as continuous olmesartan
      treatment recovered the suppressed renal ATRAP expression and inhibited the renal
      activation of p22phox, TGF-beta, fibronectin, MCP-1 and type 1 collagen. In Dahl
      Iwai salt-resistant rats, such suppression of renal ATRAP expression or induction
      of renal pathological responses by salt loading was not observed. CONCLUSIONS:
      These results indicate that prepubertal transient blockade of AT1R signaling
      exerts a long-term therapeutic effect on salt-induced hypertension and renal
      injury in Dahl Iwai salt-sensitive rats, partly through a sustained enhancement
      of renal ATRAP expression, thereby suggesting ATRAP a novel molecular target in
      salt-induced hypertension and renal injury.

PMID- 21844823
TI  - Prevalence of the Portuguese population attaining sufficient physical activity.
AB  - PURPOSE: Physical activity has many health benefits, and to implement strategies,
      mainly in those groups with insufficient levels of practice, it is important to
      evaluate physical activity. The main purpose of this study was to describe the
      prevalence of physical activity in the Portuguese population aged 10 yr and older
      using accelerometry. METHODS: The accelerometers were worn for four consecutive
      days, and a valid record was defined as at least 3 d with 10 h of wear time,
      including one weekend day. Considering these conditions, 4696 participants were
      included. RESULTS: According to the recommendations of 60 min.d(-1) of physical
      activity, 36% of participants age 10-11 yr (boys = 51.6%, girls = 22.5%) and 4%
      age 16-17 yr (boys = 7.9%, girls = 1.2%) were considered sufficiently active. In
      adulthood, ~70% of participants age 18-64 yr (men = 76.6%, women = 65.2%) and 35%
      age older than 64 yr (men = 46%, women = 29%) reached the recommendation of 30
      min.d(-1) of physical activity, when counting every minute of moderate or greater
      intensity. Considering bouts of 10 min or more of moderate or greater intensity
      in participants older than 17 yr, the prevalence was 4%-6% at 18-39 yr, 7%-9% at
      40-64 yr, and ~3% in persons age 65 yr or older. CONCLUSIONS: The design and
      implementation of strategies to promote physical activity for health among
      children and adolescents and older adults, particularly girls/women, should be
      encouraged.

PMID- 21844824
TI  - Is there anything special about valerian?

PMID- 21844825
TI  - Menopausal vasomotor symptoms and circulating hemostatic markers: causation or
      just association?

PMID- 21844826
TI  - Distinct cardioprotective effects of 17beta-estradiol and dehydroepiandrosterone
      on pressure overload-induced hypertrophy in ovariectomized female rats.
AB  - OBJECTIVE: We recently reported decreased sigma1 receptor expression in the heart
      after abdominal aortic stenosis in bilateral ovariectomized rats. Here, we use
      ovariectomized female rats to investigate the distinct cardioprotective effects
      of 17beta-estradiol (E2) and dehydroepiandrosterone (DHEA) in pressure overload
      (PO)-induced cardiac dysfunction. METHODS: E2 (0.1 mg/kg) and DHEA (30 mg/kg)
      were administered to rats subcutaneously and orally, respectively, for 14 days
      starting 2 weeks after aortic banding. RESULTS: Both E2 and DHEA treatments
      significantly inhibited PO-induced increases both in heart weight/body weight
      ratio and lung weight/body weight ratios. Both E2 and DHEA also ameliorated
      hypertrophy-induced impairment of left ventricular end-diastolic pressure, left
      ventricular-developed pressure, left ventricular contraction and relaxation (+/-
      dp/dt) rates, heart rate, and mean arterial blood pressure. Notably, DHEA but not
      E2 administration rescued decreased PO-induced sigma1 receptor reduction in the
      heart. Coadministration with N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]
      ethylamine monohydrochloride, an sigma1 receptor antagonist, inhibited DHEA
      induced amelioration of heart dysfunction without altering E2-induced
      cardioprotection. Mechanistically, both E2 and DHEA treatments significantly
      restored PO-induced decreases in protein kinase B (Akt) phosphorylation and Akt
      mediated endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1179). N,N
      Dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]-ethylamine monohydrochloride
      treatment totally abolished DHEA-induced Akt and eNOS phosphorylation without
      altering E2-induced Akt-eNOS activation. CONCLUSIONS: Taken together, these
      results from an ovariectomized rat model of PO-induced cardiac dysfunction show
      that DHEA but not E2 elicits a cardioprotective action through sigma1 receptor
      activation. DHEA-induced Akt-eNOS activation through sigma1 receptors is probably
      associated with its cardioprotective activity.

PMID- 21844827
TI  - Menopausal symptoms among healthy, middle-aged Omani women as assessed with the
      Menopause Rating Scale.
AB  - OBJECTIVE: The aim of this study was to analyze the prevalence and severity of
      climacteric symptoms and associated risk factors among a cohort of healthy,
      middle-aged Omani women. METHODS: In this cross-sectional study, 472 healthy
      Omani women between 40 and 60 years old from the representative regions of Omani
      society were surveyed using the Menopause Rating Scale. The scores obtained were
      plotted against their demographic data and menopausal stage. RESULTS: Overall,
      39.6% of the participants were premenopausal, 15.2% were perimenopausal, and
      43.6% were postmenopausal. The Menopause Rating Scale scoring showed that somatic
      and psychological symptoms occurred more frequently than did urogenital symptoms
      in all three stages. Muscle and joint pain was the most common symptom (73.3%),
      followed by mental and physical exhaustion (47.2%) and anxiety (46.6%). An
      increase in the mean scores for both somatic and psychological symptoms and their
      severity was observed when the following factors were present: progression of
      menopausal stage (mean +/- SD, 22.5 +/- 2.6, 3.6 +/- 2.9, 4.5 +/- 3.2), old age
      (4.2 +/- 3.2) versus young age (2.9 +/- 2.6), single (4.3 +/- 3.3) versus married
      (3.3 +/- 2.9), illiterate (3.9 +/- 3.1) versus educated (2.7 +/- 2.6), and
      sexually inactive (4.4 +/- 3.4) versus sexually active (3.1 +/- 2.7).
      CONCLUSIONS: Omani women were found to exhibit highly atypical symptoms of
      menopause. Increased severity of symptoms was found to be related to age,
      advanced stage of menopause, and lower educational level.

PMID- 21844828
TI  - Otoscopic signs of otitis media.
AB  - BACKGROUND: Lack of agreed-upon diagnostic criteria for acute otitis media (AOM)
      has led to inconsistencies in clinical care, misleading research results, and
      misguided educational efforts. The objective of this study was to examine
      findings that expert otoscopists use when diagnosing AOM. METHODS: A group of
      experienced otoscopists examined 783 children presenting for primary care. In
      addition, endoscopic still images of the tympanic membranes (TMs) were obtained.
      A random sample of 135 of these images was sent for review to a group of 7
      independent physicians who were expert otoscopists. We examined the findings that
      both groups of observers used to distinguish between AOM, otitis media with
      effusion (OME), and no effusion. RESULTS: Among both groups of observers, bulging
      of the TM was the finding judged best to differentiate AOM from OME: 96% of ears
      and 93% of ear image evaluations assigned a diagnosis of AOM by members of the 2
      groups were reported as showing bulging of the TM, compared with 0% and 3%,
      respectively, of ears and ear image evaluations assigned a diagnosis of OME.
      Opacification of the TM was the finding that best differentiated OME from no
      effusion. CONCLUSIONS: We describe findings that are used by experienced
      otoscopists to diagnose AOM and OME. The findings point to the advisability under
      most circumstances of restricting antimicrobial treatment for AOM to children who
      have TM bulging, and they call into question clinical trials of the treatment of
      AOM in which TM bulging has not been a required element for participation.

PMID- 21844829
TI  - Ethanol locks therapy for resolution of fungal catheter infections.
AB  - Ethanol locks have been used to treat catheter infections and to decrease the
      rate at which they occur. Catheter-related infections caused by Candida spp. are
      especially difficult to manage medically and usually require catheter removal. We
      report 3 consecutive patients whose catheter infections caused by Candida were
      successfully treated with a combination of ethanol lock therapy and systemic
      antifungals.

PMID- 21844830
TI  - Patient relapse in the context of drug abuse treatment.
AB  - How do addiction treatment programs integrate the expectation of relapse into
      drug abuse treatment? This article serves as a thought piece to pose questions
      rather than definitive solutions. It reflects a distillation of discussions that
      occurred at the National Institute on Drug Abuse meeting titled "Program Response
      to Patient Relapse," held on July 15, 2009, along with quantitative and
      qualitative information about the patterns and types of discharge policies, which
      factors influence them, and how the culture of drug abuse treatment and the
      personnel interact with this issue. Some existing data on the discharging of
      relapsed patients are identified. A program's response to relapse is usually
      guided by its setting (level of care), philosophy (abstinence vs risk behavior
      reduction), and associated patient behavior ("benign" vs program disruptive). Key
      questions examined in this context include the following: Can different discharge
      policies impact a patient's access to treatment, and what are the implications of
      incorporating a medical model of addiction into discharge policies?

PMID- 21844831
TI  - Open-label pilot study of extended-release naltrexone to reduce drinking and
      driving among repeat offenders.
AB  - OBJECTIVES: A high proportion of persons convicted of driving while impaired
      repeat the offense. Many continue drinking and driving, even when faced with long
      jail terms. Hence, they pose a serious public health threat. This preliminary
      study evaluated extended-release, injectable naltrexone suspension (XR-NTX) and
      supportive therapy in reducing (1) drinking and (2) attempts to drive after
      drinking among repeat driving while impaired offenders with an ignition interlock
      device installed in their vehicles. METHODS: Treatment-seeking volunteers
      received medical management therapy and 3 monthly injections of XR-NTX. We
      compared data on alcohol consumption, alcohol biomarkers, and interlock
      information before, during, and after treatment using summary measures and Sign
      tests. RESULTS: Of 12 consented subjects, 10 received at least 1 injection, and 7
      received all 3 injections. All subjects receiving medication reported a decrease
      in average drinks per day (P < 0.01) and abstinent days (P = 0.02) while on
      treatment versus pretreatment levels. Average daily drinks decreased by 77%, from
      3.0 to 0.69 (P < 0.01), during treatment with XR-NTX. Average drinks per drinking
      day also declined by 39% during treatment, from 6.6 to 4.0 (P = 0.04). Percent
      days abstinent increased by 31%, from 56.8 to 81.96 (P = 0.02), which persisted
      after treatment completion. Biomarkers were consistent with reduced drinking. The
      percentage of vehicular failures to start due to elevated breath alcohol
      decreased from 3.1% of tests to 1.29% of tests. CONCLUSIONS: A randomized,
      controlled clinical trial is needed to demonstrate the efficacy of this promising
      treatment regimen for repeat offenders.

PMID- 21844832
TI  - A simple, novel method for assessing medication adherence: capsule photographs
      taken with cellular telephones.
AB  - OBJECTIVES: Medication nonadherence is an important factor in clinical practice
      and research methodology. Although many methods of measuring adherence have been
      investigated, there is as yet no "gold standard." We compared the usefulness and
      accuracy of a novel measure of adherence, photographs taken by cellular
      telephones with 2 incumbents: capsule count and the Medication Event Monitoring
      System (MEMS). METHOD: Twenty subjects participated in a clinical trial of the
      efficacy of modafinil for the treatment of methamphetamine dependence. Subjects
      were issued cell phones and medication in MEMS Cap equipped bottles and were
      instructed to take 1 capsule a day for 8 weeks, recording adherence with both
      systems. Pill counts were recorded at weekly inpatient visits. Subjects were paid
      for participation and for each capsule photograph and the returned medication
      bottle with MEMS Cap. RESULTS: Capsule count-indicated adherence (proportion of
      prescribed medication taken) was 94.9%. When compared with capsule count, the
      novel method was found to underestimate adherence, whereas MEMS overestimated
      adherence. By using the dosing time data collected, we determined that subjects
      who dosed at a consistent time daily were more likely to adhere to the prescribed
      regimen. We also detected discrepancies in the timestamps recorded by MEMS.
      CONCLUSIONS: Capsule photographs are a useful measure of adherence, allowing more
      accurate time measures and more frequent adherence assessment than MEMS or
      capsule count. Given the ubiquity of cellular telephone use, and the relative
      ease of this adherence measurement method, we believe it is a useful and cost
      effective approach.

PMID- 21844833
TI  - Illicit use of buprenorphine/naloxone among injecting and noninjecting opioid
      users.
AB  - OBJECTIVES: We examined the use, procurement, and motivations for the use of
      diverted buprenorphine/naloxone among injecting and noninjecting opioid users in
      an urban area. METHODS: A survey was self-administered among 51 injecting opioid
      users and 49 noninjecting opioid users in Providence, RI. Participants were
      recruited from a fixed-site syringe exchange program and a community outreach
      site between August and November 2009. RESULTS: A majority (76%) of participants
      reported having obtained buprenorphine/naloxone illicitly, with 41% having done
      so in the previous month. More injection drug users (IDUs) than non-IDUs reported
      the use of diverted buprenorphine/naloxone (86% vs 65%, P = 0.01). The majority
      of participants who had used buprenorphine/naloxone reported doing so to treat
      opioid withdrawal symptoms (74%) or to stop using other opioids (66%) or because
      they could not afford drug treatment (64%). More IDUs than non-IDUs reported
      using diverted buprenorphine/naloxone for these reasons. Significantly more non
      IDUs than IDUs reported ever using buprenorphine/naloxone to "get high" (69% vs
      32%, P < 0.01). The majority of respondents, both IDUs and non-IDUs, were
      interested in receiving treatment for opioid dependence, with greater reported
      interest in buprenorphine/naloxone than in methadone. Common reasons given for
      not being currently enrolled in a buprenorphine/naloxone program included cost
      and unavailability of prescribing physicians. CONCLUSIONS: The use of diverted
      buprenorphine/naloxone was common in our sample. However, many opioid users,
      particularly IDUs, were using diverted buprenorphine/naloxone for reasons
      consistent with its therapeutic purpose, such as alleviating opioid withdrawal
      symptoms and reducing the use of other opioids. These findings highlight the need
      to explore the full impact of buprenorphine/naloxone diversion and improve the
      accessibility of buprenorphine/naloxone through licensed treatment providers.

PMID- 21844834
TI  - The source of methadone in overdose deaths in Western Virginia in 2004.
AB  - OBJECTIVES: Methadone-related overdose deaths increased in the United States by
      468% from 1999 to 2005. Current studies associate the nonmedical use of methadone
      with methadone-related deaths. This study describes medical examiner cases in
      rural Virginia in 2004 with methadone identified by toxicology and compares cases
      according to source of methadone. METHODS: In 2004, all intentional and
      unintentional poisoning deaths from the Office of The Chief Medical Examiner,
      Western District of Virginia, were reviewed to identify cases in which methadone
      was a direct or contributing cause of death. The Virginia Prescription Monitoring
      Program was reviewed for prescription opioids in the name of these identified
      decedents. Decedent participation in local opioid treatment programs (OTP) was
      also assessed. RESULTS: The source of methadone in the 61 methadone-related
      overdose deaths was mostly nonprescribed (67%), although 28% of decedents were
      prescribed methadone for analgesia. Only 5% of decedents were actively enrolled
      in an OTP. The majority of deaths were attributed to polysubstance overdose.
      CONCLUSIONS: The majority of methadone overdose deaths in this study were related
      to illicit methadone use, rather than prescribed or OTP uses. Interventions to
      decrease methadone-related deaths should focus on reduction of nonprescription
      use of methadone.

PMID- 21844835
TI  - Impaired decision making in opiate addiction correlates with anxiety and self
      directedness but not substance use parameters.
AB  - BACKGROUND: Despite a large number of empirical reports of impaired decision
      making in substance use disorders, the underlying factors contributing to such
      deficits remain to be elucidated. This study examined the potential influences of
      personality traits, affective symptoms, and pharmacological variables on decision
      making, as measured by the Iowa Gambling Task (IGT) in a sample of opioid
      dependent patients. METHODS: A total of 46 opioid-dependent patients taking part
      in an opiate maintenance outpatient program and 46 healthy control subjects
      performed the IGT. Personality traits and affective symptoms were examined by
      using Zuckerman Sensation-Seeking Scale, the State-Trait Anxiety Inventory and
      Beck Depression Inventory. In addition, Cloninger Temperament and Character
      Inventory was administered in the patient group. Information on current and life
      time substance use was acquired with a standardized interview. RESULTS: Opioid
      dependent patients performed significantly worse on the IGT than controls. This
      difference disappeared after statistically controlling for trait anxiety, state
      anxiety, disinhibition, depressive symptoms, and lifetime alcohol consumption.
      Trait and state anxiety and self-directedness were significantly associated with
      the IGT final score. Hierarchical regression analyses suggested that self
      directedness differentially moderated the relationships between the anxiety
      variables and IGT performance. CONCLUSIONS: The decision-making impairments
      observed in opioid-dependent patients are influenced by current levels of anxiety
      and the personality markers trait anxiety and self-directedness. Differences in
      decision making between opioid-dependent and healthy individuals may also be due
      to differences in other personality facets, affective symptoms, and alcohol
      consumption. Amount of opioid and other substance intake did not show any
      effects. These results indicate that psychological characteristics may have a
      higher impact on decision-making performance than drug-induced pharmacological
      effects.

PMID- 21844836
TI  - Low risk for hepatitis C seroconversion in methadone maintenance treatment.
AB  - OBJECTIVES: To study the risk factors for seroconversion to hepatitis C virus
      (HCV) infection since admission to methadone maintenance treatment (MMT) and to
      characterize the seronegative admitted group. METHODS: All 657 patients admitted
      to our MMT clinic in Tel Aviv, Israel, between 1993 and 2008 were prospectively
      followed up. Those who were HCV negative (n = 271) with >1 HCV tests (n = 207)
      were included for seroconversion analyses. RESULTS: Proportions of ever drug
      injectors, benzodiazepine abuse, and former USSR immigrants were higher among HCV
      sera-positive versus sera-negative patients on admission to MMT. The incidence of
      HCV seroconversion in MMT was 2/100 person years [py] (25 seroconversions, 1133.9
      py). Seroconversion rates were higher among 44 younger patients (<30 years:
      9.6/100 vs 1.4/100 py, P < 0.0005), among 103 patients with positive urine
      results to benzodiazepines (3.6/100 vs 1/100 py, P = 0.005), among 118 patients
      who injected the drugs (3.9/100 vs 1/100 py, P = 0.003), and among 43 patients
      who dropped out and were readmitted to the MMT (4.3/100 vs 1.7/100 py, P = 0.04).
      There was a trend of higher seroconversion among 61 females (P = 0.1), among 62
      patients with no children (P = 0.1), and among those having hepatitis B antigen
      (n = 7; P = 0.09). Variables that predicted seroconversion were drug injection,
      benzodiazepine abuse, and being younger at admission to MMT. Being a former USSR
      immigrant did not predict seroconversion. CONCLUSIONS: The HCV seroconversion
      rate of patients in MMT is low, also, for former USSR immigrants. The predictors
      for seroconversion were only admission variables (younger age at admission to
      MMT, ever drug injector, and having positive urine to benzodiazepines at MMT
      admission). Specific intervention to eliminate seroconversion is needed for these
      high-risk groups.

PMID- 21844837
TI  - Self-reported alcohol and drug use in pregnant young women: a pilot study of
      associated factors and identification.
AB  - OBJECTIVES: This study describes the factors associated with self-reported
      substance use in pregnant young women attending a hospital clinic and evaluates 3
      ways in its identification. METHODS: A cross-sectional study of 30 pregnant young
      adults who responded to a mail survey containing the CRAFFT screening tool. All
      completed a diagnostic interview that included self-report information on their
      use of alcohol and drugs before and during pregnancy, the T-ACE screening tool,
      and the contexts in which they would be likely to use. Medical records were
      reviewed. RESULTS: One-third of participants consumed alcohol, marijuana, or both
      while pregnant. Many had lifetime diagnoses of alcohol (23%) or cannabis (30%)
      use disorders, but only 1 met criteria for current diagnosis. Age, race,
      education, and children at home were not associated with either prenatal alcohol
      or cannabis use. Before pregnancy, alcohol drinking was associated with prenatal
      alcohol use (P = .02) and prenatal cannabis use (P = .06). Another trend of the
      before-pregnancy cannabis use being associated with prenatal cannabis use (P =
      .08) was observed. Most participants indicated little likelihood of substance use
      in convivial, intimate, or negative coping contexts while pregnant. However,
      participants with prenatal substance use had significantly higher convivial (P =
      .02) and intimate (P = .01) subscale scores of the Drinking Context Scale before
      pregnancy. Compared to the medical record and the T-ACE, the CRAFFT was best in
      identifying prenatal substance use (c-statistic = 0.9). CONCLUSIONS: The CRAFFT
      screening instrument and asking about the contexts during which alcohol might
      have been consumed before pregnancy are promising approaches in the
      identification of prenatal substance use.

PMID- 21844838
TI  - Bethanechol for buprenorphine-related urinary hesitancy: a case series.
AB  - Constipation is a well-known side effect of buprenorphine, but urinary hesitancy
      is less frequently discussed and may go unrecognized. Reported are the 2 cases of
      men older than 50 years who experienced disabling urinary hesitancy with
      buprenorphine and naloxone combination (suboxone) and were successfully treated
      with bethanechol, a cholinergic medication.

PMID- 21844839
TI  - Anatomical correlates to the bands seen in the outer retina by optical coherence
      tomography: literature review and model.
AB  - PURPOSE: To evaluate the validity of commonly used anatomical designations for
      the four hyperreflective outer retinal bands seen in current-generation optical
      coherence tomography, a scale model of outer retinal morphology was created using
      published information for direct comparison with optical coherence tomography
      scans. METHODS: Articles and books concerning histology of the outer retina from
      1900 until 2009 were evaluated, and data were used to create a scale model
      drawing. Boundaries between outer retinal tissue compartments described by the
      model were compared with intensity variations of representative spectral-domain
      optical coherence tomography scans using longitudinal reflectance profiles to
      determine the region of origin of the hyperreflective outer retinal bands.
      RESULTS: This analysis showed a high likelihood that the spectral-domain optical
      coherence tomography bands attributed to the external limiting membrane (the
      first, innermost band) and to the retinal pigment epithelium (the fourth,
      outermost band) are correctly attributed. Comparative analysis showed that the
      second band, often attributed to the boundary between inner and outer segments of
      the photoreceptors, actually aligns with the ellipsoid portion of the inner
      segments. The third band corresponded to an ensheathment of the cone outer
      segments by apical processes of the retinal pigment epithelium in a structure
      known as the contact cylinder. CONCLUSION: Anatomical attributions and subsequent
      pathophysiologic assessments pertaining to the second and third outer retinal
      hyperreflective bands may not be correct. This analysis has identified testable
      hypotheses for the actual correlates of the second and third bands. Nonretinal
      pigment epithelium contributions to the fourth band (e.g., Bruch membrane) remain
      to be determined.

PMID- 21844840
TI  - Analgesic and anti-inflammatory activities of salicylaldehyde 2-chlorobenzoyl
      hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone
      (H(2)LASSBio-1064) and their zinc(II) complexes.
AB  - Salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4
      chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their complexes [Zn(LASSBio
      466)H(2)O](2) (1) and [Zn(HLASSBio-1064)Cl](2) (2) were evaluated in animal
      models of peripheral and central nociception, and acute inflammation. All studied
      compounds significantly inhibited acetic acid-induced writhing response. Upon
      coordination the anti-nociceptive activity was favored in the complex 1.
      H(2)LASSBio-466 inhibited only the first phase of the formalin test, while 1 was
      active in the second phase, like indomethacin, indicating its ability to inhibit
      nociception associated with the inflammatory response. Hence coordination to
      zinc(II) altered the pharmacological profile of H(2)LASSBio-466. H(2)LASSBio-1064
      inhibited both phases but this effect was not improved by coordination. The
      studied compounds did not increase the latency of response in the hot plate
      model, indicating their lack of central anti-nociceptive activity. All compounds
      showed levels of inhibition of zymosan-induced peritonitis comparable or superior
      to indomethacin, indicating an expressive anti-inflammatory profile.

PMID- 21844841
TI  - Selective covalent conjugation of phosphorothioate DNA oligonucleotides with
      streptavidin.
AB  - Protein-DNA conjugates have found numerous applications in the field of
      diagnostics and nanobiotechnology, however, their intrinsic susceptibility to DNA
      degradation by nucleases represents a major obstacle for many applications. We
      here report the selective covalent conjugation of the protein streptavidin (STV)
      with phosphorothioate oligonucleotides (psDNA) containing a terminal
      alkylthiolgroup as the chemically addressable linking unit, using a
      heterobifunctional NHS-/maleimide crosslinker. The psDNA-STV conjugates were
      synthesized in about 10% isolated yields. We demonstrate that the terminal
      alkylthiol group selectively reacts with the maleimide while the backbone sulfur
      atoms are not engaged in chemical conjugation. The novel psDNA-STV conjugates
      retain their binding capabilities for both biotinylated macromolecules and the
      complementary nucleic acid. Moreover, the psDNA-STV conjugate retained its
      binding capacity for complementary oligomers even after a nuclease digestion
      step, which effectively degrades deoxyribonucleotide oligomers and thus the
      binding capability of regular DNA-STV conjugates. The psDNA-STV therefore hold
      particular promise for applications e.g. in proteome research and novel
      biosensing devices, where interfering endogenous nucleic acids need to be removed
      from analytes by nuclease digestion.

PMID- 21844842
TI  - A comparative study of physical and chemical processes for removal of biomass in
      biofilters.
AB  - After 6 months of operation a long-term biofilter was stopped for two weeks and
      then it was started up again for a second experimental period of almost 1.3
      years, with high toluene loads and submitted to several physical and chemical
      treatments in order to remove excess biomass that could affect the reactor's
      performance due to clogging, whose main effect is a high pressure drop.
      Elimination capacity and removal efficiency were determined after each treatment.
      The methods applied were: filling with water and draining, backwashing, and air
      sparging. Different flows and temperatures (20, 30, 45 and 60  degrees C) were
      applied, either with distilled water or with different chemicals in aqueous
      solutions. Treatments with chemicals caused a decrease of the biofilter
      performance, requiring periods of 1 to 2 weeks to recover previous values. The
      results indicate that air sparging with pure distilled water as well as with
      solutions of NaOH (0.01% w/v) and NaOCl (0.01% w/v) were the treatments that
      removed more biomass, working either at 20, 30 or 45  degrees C and at relatively
      low flow rates (below 320 L h(-1)), but with a high biodegradation inhibition
      after the treatments. Dry biomass (g VS) content was determined at three
      different heights of the biofilter in order to carry out each experiment under
      the same conditions. The same amount of dry biomass when applying a treatment was
      established so it could be considered that the biofilm conditions were identical.
      Wet biomass was used as a control of the biofilter's water content during
      treatments. Several batch assays were performed to support and quantify the
      observed inhibitory effects of the different chemicals and temperatures applied.

PMID- 21844843
TI  - Synthesis of porphyrin-dendrimers with a pyrene in the periphery and their cubic
      nonlinear optical properties.
AB  - Dendrons of pyrene derivatives were attached to a porphyrin core. A marked effect
      in solution for the dendrimers was observed in the absorption spectra. All the
      compounds obtained were characterized by (1)H-, (13)C-NMR, FTIR, UV-vis, MALDI
      TOF or FAB+ mass spectrometry and elemental analysis. The cubic nonlinear optical
      behavior of some the synthesized compounds was tested via Z-Scan measurements in
      spin-coated film samples.

PMID- 21844844
TI  - Antimicrobial and antioxidant activities of new metal complexes derived from 3
      aminocoumarin.
AB  - 3-Aminocoumarin (L) has been synthesized and used as a ligand for the formation
      of Cr(III), Ni(II), and Cu(II) complexes. The chemical structures were
      characterized using different spectroscopic methods. The elemental analyses
      revealed that the complexes where M=Ni(II) and Cu(II) have the general formulae
      [ML(2)Cl(2)], while the Cr(III) complex has the formula [CrL(2)Cl(2)]Cl. The
      molar conductance data reveal that all the metal chelates, except the Cr(III)
      one, are non-electrolytes. From the magnetic and UV-Visible spectra, it is found
      that these complexes have octahedral structures. The stability for the prepared
      complexes was studied theoretically using Density Function Theory. The total
      energy for the complexes was calculated and it was shown that the copper complex
      is the most stable one. Complexes were tested against selected types of microbial
      organisms and showed significant activities. The free radical scavenging activity
      of metal complexes have been determined by measuring their interaction with the
      stable free radical DPPH and all the compounds have shown encouraging antioxidant
      activities.

PMID- 21844845
TI  - Pectoral muscle identification in mammograms.
AB  - In most of the approaches of computer-aided detection of breast cancer, one of
      the preprocessing steps applied to the mammogram is the removal/suppression of
      pectoral muscle, as its presence within the mammogram may adversely affect the
      outcome of cancer detection processes. Through this study, we propose an
      efficient automatic method using the watershed transformation for identifying the
      pectoral muscle in mediolateral oblique view mammograms. The watershed
      transformation of the mammogram shows interesting properties that include the
      appearance of a unique watershed line corresponding to the pectoral muscle edge.
      In addition to this, it is observed that the pectoral muscle region is
      oversegmented due to the existence of several catchment basins within the
      pectoral muscle. Hence, a suitable merging algorithm is proposed to combine the
      appropriate catchment basins to obtain the correct pectoral muscle region. A
      total of 84 mammograms from the mammographic image analysis database were used to
      validate this approach. The mean false positive and mean false negative rates,
      obtained by comparing the results of the proposed approach with manually
      identified (ground truth) pectoral muscle boundaries, respectively, were 0.85%
      and 4.88%. A comparison of the results of the proposed method with related state
      of-the-art methods shows that the performance of the proposed approach is better
      than the existing methods in terms of the mean false negative rate. Using
      Hausdorff distance metric, the comparison of the results of the proposed method
      with ground truth shows low Hausdorff distances, the mean and standard deviation
      being 3.85 +/- 1.07 mm.

PMID- 21844846
TI  - Feasibility of using two-dimensional array dosimeter for in vivo dose
      reconstruction via transit dosimetry.
AB  - Two-dimensional array dosimeters are commonly used to perform pretreatment
      quality assurance procedures, which makes them highly desirable for measuring
      transit fluences for in vivo dose reconstruction. The purpose of this study was
      to determine if an in vivo dose reconstruction via transit dosimetry using a 2D
      array dosimeter was possible. To test the accuracy of measuring transit dose
      distribution using a 2D array dosimeter, we evaluated it against the measurements
      made using ionization chamber and radiochromic film (RCF) profiles for various
      air gap distances (distance from the exit side of the solid water slabs to the
      detector distance; 0 cm, 30 cm, 40 cm, 50 cm, and 60 cm) and solid water slab
      thicknesses (10 cm and 20 cm). The backprojection dose reconstruction algorithm
      was described and evaluated. The agreement between the ionization chamber and RCF
      profiles for the transit dose distribution measurements ranged from -0.2% ~ 4.0%
      (average 1.79%). Using the backprojection dose reconstruction algorithm, we found
      that, of the six conformal fields, four had a 100% gamma index passing rate (3%/3
      mm gamma index criteria), and two had gamma index passing rates of 99.4% and
      99.6%. Of the five IMRT fields, three had a 100% gamma index passing rate, and
      two had gamma index passing rates of 99.6% and 98.8%. It was found that a 2D
      array dosimeter could be used for backprojection dose reconstruction for in vivo
      dosimetry.

PMID- 21844847
TI  - A new method to deliver supraclavicular radiation in breast radiotherapy for lung
      sparing.
AB  - Due to the angulation of the breast board used for tangential breast irradiation,
      additional normal lung tissues are included in the supraclavicular field. This
      work investigates a method to reduce the lung volume and dose delivered during
      supraclavicular irradiation for breast cancer. Ten patients included for this
      retrospective study received chest wall and supraclavicular irradiation following
      radical surgery or breast-conserving surgery. Three-dimensional conformal
      radiation therapy plans were generated using the CMS XiO treatment planning
      system. The clinical target volume (CTV) of the supraclavicular irradiation is
      defined as the subcutaneous tissues from 0.5 cm under the anterior skin surface
      to a 3 cm depth. Only the ipsilateral lung is defined as the organ at risk. In
      the new method, the couch is rotated 90 degrees  and the supraclavicular field is
      tilted to maintain a normal incident angle to the breast board rather than the
      couch surface to spare more normal lung tissues. The absolute volume of the
      ipsilateral lung irradiated, and the volumes of lung tissues receiving 5 Gy and
      20 Gy (V5 and V20) are analyzed. The new method can reduce the lung volume
      irradiated by the supraclavicular field significantly. For the ten patients
      investigated, only 5.3% of the ipsilateral lung is irradiated with the new
      method, while 14.9% of the ipsilateral lung is irradiated using the conventional
      method. Compared with the conventional method, the new method reduces V5 by 53.6%
      and V20 by 59.0%. Our new method does not alter the patient positioning for
      breast treatment but rotates the couch to deliver a tilted supraclavicular field
      to maintain adequate CTV coverage and spare more normal lung tissues. The results
      of this study demonstrated that our new method is effective, and that the
      reduction of normal lung tissue volume in the field is significant.

PMID- 21844848
TI  - Dosimetric impact of density variations in Solid Water 457 water-equivalent
      slabs.
AB  - The purpose of this study was to determine the dosimetric impact of density
      variations observed in water-equivalent solid slabs. Measurements were performed
      using two 30 cm * 30 cm water-equivalent slabs, one being 4 cm think and the
      other 5 cm thick. The location and extent of density variations were determined
      by computed tomography (CT) scans. Additional imaging measurements were made with
      an amorphous silicon megavoltage portal imaging device and an ultrasound unit.
      Dosimetric measurements were conducted with a 2D ion chamber array, and a scanned
      diode in water. Additional measurements and calculations were made of small
      rectilinear void inhomogeneities formed with water-equivalent slabs, using a 2D
      ion chamber array and the convolution superposition algorithm. Two general types
      of density variation features were observed on CT images: 1) regions of many
      centimeters across, but typically only a few millimeters thick, with electron
      densities a few percent lower than the bulk material, and 2) cylindrical regions
      roughly 0.2 cm in diameter and up to 20 cm long with electron densities up to 5%
      lower than the surrounding material. The density variations were not visible on
      kilovoltage, megavoltage or ultrasound images. The dosimetric impact of the
      density variations were not detectable to within 0.1% using the 2D ion chamber
      array or the scanning photon diode at distances 0.4 cm to 2 cm beyond the
      features. High-resolution dosimetric calculations using the convolution
      superposition algorithm with density corrections enabled on CT-based datasets
      showed no discernable dosimetric impact. Calculations and measurements on
      simulated voids place the upper limit on possible dosimetric variations from
      observed density variations at much less than 0.6%. CT imaging of water
      equivalent slabs may reveal density variations which are otherwise unobserved
      with kV, MV, or ultrasound imaging. No dosimetric impact from these features was
      measureable with an ion chamber array or scanned photon diode. Consequently, they
      were determined to be acceptable for all clinical use.

PMID- 21844849
TI  - Collision indicator charts for gantry-couch position combinations for Varian
      linacs.
AB  - The use of non-coplanar radiation fields can potentially lead to collisions
      between the gantry and the couch or patient. The collisions are often not
      realized until the plan is finished and the fields are checked on the machine, or
      even later when the patient is already on the table. This paper presents an easy
      method of gauging if a collision is likely between the gantry and couch or
      patient during treatment planning. The method involves creating a chart of
      allowable gantry and couch combinations. The charts contain curves on a polar
      graph of the gantry and couch angle "plane". The curves display the limits of
      collisions for each gantry and couch combination for vertical couch positions 10,
      15 and 20 cm below isocenter and for couch lateral positions of -10, 0, +10 cm,
      covering the majority of couch positions encountered in patient treatments. All
      combinations in the region within the curves (containing the origin) are valid,
      while all combinations outside the curves will result in a collision. The data
      for the charts are collected from measurements of the gantry angle that just
      clears each couch angle. The patient presence was modeled by placing a
      stereotactic body frame on the top of the couch. Separate charts were created for
      couch angles between 0 degrees  and 90 degrees  and between 360 degrees  and 270
      degrees  over all gantry angles. The graphs are easy to create, implement, and
      use in the clinic and help reduce the time, complications, and uncertainties of
      planning with non-coplanar fields.

PMID- 21844850
TI  - Understanding the impact of RapidArc therapy delivery errors for prostate cancer.
AB  - The purpose of this study is to simulate random and systematic RapidArc delivery
      errors for external beam prostate radiotherapy plans in order to determine the
      dose sensitivity for each error type. Ten prostate plans were created with a
      single 360 degrees  arc. The DICOM files for these treatment plans were then
      imported into an in-house computer program that introduced delivery errors.
      Random and systematic gantry position (0.25 degrees , 0.5 degrees , 1 degrees ),
      monitor unit (MU) (1.25%, 2.5%, 5%), and multileaf collimator (MLC) position
      (0.5, 1, 2 mm) errors were introduced. The MLC errors were either random or one
      of three types of systematic errors, where the MLC banks moved in the same (MLC
      gaps remain unchanged) or opposing directions (increasing or decreasing the MLC
      gaps). The generalized equivalent uniform dose (gEUD) was calculated for the
      original plan and all treatment plans with errors introduced. The dose
      sensitivity for the cohort was calculated using linear regression for the gantry
      position, MU, and MLC position errors. Because there was a large amount of
      variability for systematic MLC position errors, the dose sensitivity of each plan
      was calculated and correlated with plan MU, mean MLC gap, and the percentage of
      MLC leaf gaps less than 1 and 2 cm for each individual plan. We found that random
      and systematic gantry position errors were relatively insignificant (< 0.1% gEUD
      change) for gantry errors up to 1 degrees . Random MU errors were also
      insignificant, and systematic MU increases caused a systematic increase in gEUD.
      For MLC position errors, random MLC errors were relatively insignificant up to 2
      mm as had been determined in previous IMRT studies. Systematic MLC shift errors
      caused a decrease of approximately -1% in the gEUD per mm. For systematic MLC gap
      open errors, the dose sensitivity was 8.2%/mm and for MLC gap close errors the
      dose sensitivity was -7.2%/mm. There was a large variability for MLC gap
      open/close errors for the ten RapidArc plans which correlated strongly with MU,
      mean gap width, and percentage of MLC gaps less than 1 or 2cm. This study
      evaluates the magnitude of various simulated RapidArc delivery errors by
      calculating gEUED on various prostate plans.

PMID- 21844851
TI  - 3D heterogeneous dose distributions for total body irradiation patients.
AB  - One major objective of total body irradiation (TBI) treatments is to deliver a
      uniform dose in the entire body of the patient. Looking at 3D dose distributions
      for constant speed (CstSpeed) and variable speed (VarSpeed) translating couch TBI
      treatments, dose uniformity and the effect of body heterogeneities were
      evaluated. This study was based on retrospective dose calculations of 10 patients
      treated with a translating couch TBI technique. Dose distributions for CstSpeed
      and VarSpeed TBI treatments have been computed with Pinnacle3 treatment planning
      system in homogeneous (Homo) and heterogeneous (Hetero) dose calculation modes. A
      specific beam model was implemented in Pinnacle3 to allow an accurate dose
      calculation adapted for TBI special aspects. Better dose coverages were obtained
      with Homo/VarSpeed treatments compared to Homo/CstSpeed cases including smaller
      overdosage areas. Large differences between CstSpeed and VarSpeed dose
      calculations were observed in the brain, spleen, arms, legs, and lateral parts of
      the abdomen (differences between V100% mean values up to 57.5%). Results also
      showed that dose distributions for patients treated with CstSpeed TBI greatly
      depend on the patient morphology, especially for pediatric and overweight cases.
      Looking at heterogeneous dose calculations, underdosages (2%-5%) were found in
      high-density regions (e.g., bones), while overdosages (5%-15%) were found in low
      density regions (e.g., lungs). Overall, Homo/CstSpeed and Hetero/VarSpeed dose
      distributions showed more hot spots than Homo/VarSpeed and were greatly dependent
      on patient anatomy. CstSpeed TBI treatments allow a simple optimization process
      but lead to less dose uniformity due to the patient anatomy. VarSpeed TBI
      treatments require more complex dose optimization, but lead to a better dose
      uniformity independent of the patient morphology. Finally, this study showed that
      heterogeneities should be considered in dose calculations in order to obtain a
      better optimization and, therefore, to improve dose uniformity.

PMID- 21844852
TI  - Dosimetric consequences of rotational setup errors with direct simulation in a
      treatment planning system for fractionated stereotactic radiotherapy.
AB  - The purpose was to determine dose-delivery errors resulting from systematic
      rotational setup errors for fractionated stereotactic radiotherapy using direct
      simulation in a treatment planning system. Ten patients with brain tumors who
      received intensity-modulated radiotherapy had dose distributions re-evaluated to
      assess the impact of systematic rotational setup errors. The dosimetric effect of
      rotational setup errors was simulated by rotating images and contours using a 3
      by 3 rotational matrix. Combined rotational errors of +/- 1 degrees , +/- 3
      degrees , +/- 5 degrees  and +/- 7 degrees  and residual translation errors of 1
      mm along each axis were simulated. Dosimetric effects of the rotated images were
      evaluated by recomputing dose distributions and compared with the original plan.
      The mean volume of CTV that received the prescription dose decreased from 99.3%
      +/- 0.5% (original) to 98.6% +/- 1.6% (+/- 1 degrees ), 97.0% +/- 2.0% (+/- 3
      degrees ), 93.1% +/- 4.6% (+/- 5 degrees ), and 87.8% +/- 14.2% (+/- 7 degrees ).
      Minimal changes in the cold and hot spots were seen in the CTV. In general, the
      increase in the volumes of the organs at risk (OARs) receiving the tolerance
      doses was small and did not exceed the tolerance, except for cases where the OARs
      were in close proximity to the PTV. For intracranial tumors treated with IMRT
      with a CTV-to-PTV margin of 3 mm, rotational setup errors of 3 degrees  or less
      didn't decrease the CTV coverage to less than 95% in most cases. However, for
      large targets with irregular or elliptical shapes, the target coverage decreased
      significantly as rotational errors of 5 degrees  or more were present. Our
      results indicate that setup margins are warranted even in the absence of
      translational setup errors to account for rotational setup errors. Rotational
      setup errors should be evaluated carefully for clinical cases involving large
      tumor sizes and for targets with elliptical or irregular shape, as well as when
      isocenter is away from the center of the PTV or OARs are in close proximity to
      the target volumes.

PMID- 21844853
TI  - Initial experience and clinical comparison of two image guidance methods for SBRT
      treatment: 4DCT versus respiratory-triggered imaging.
AB  - For Stereotactic Body Radiation Therapy (SBRT) treatment of lung and liver, we
      quantified the differences between two image guidance methods: 4DCT and ExacTrac
      respiratory-triggered imaging. Five different patients with five liver lesions
      and one lung lesion for a total of 19 SBRT delivered fractions were studied. For
      the 4DCT method, a manual registration process was used between the 4DCT image
      sets from initial simulation and treatment day to determine the required daily
      image-guided corrections. We also used the ExacTrac respiratory-triggered imaging
      capability to verify the target positioning, and calculated the differences in
      image guidance shifts between these two methods. The mean (standard deviation) of
      the observed differences in image-guided shifts between 4DCT and ExacTrac
      respiratory-triggered image guidance was left/right (L/R) = 0.4 (2.0) mm,
      anterior/posterior (A/P) = 1.4 (1.7) mm, superior/inferior (S/I) = 2.2 (2.0) mm,
      with no difference larger than 5.0 mm in any given direction for any individual
      case. The largest error occurred in the S/I direction, with a mean of 2.2 mm for
      the six lesions. This seems reasonable, because respiratory motion and the
      resulting imaging uncertainties are most pronounced in this S/I direction. Image
      guidance shifts derived from ExacTrac triggered imaging at two extreme breathing
      phases (i.e., full exhale vs. full inhale), agreed well (less than 2.0 mm) with
      each other. In summary, two very promising image guidance methods of 4DCT and
      ExacTrac respiratory-triggered imaging were presented and the image guidance
      shifts were comparable for the patients evaluated in this study.

PMID- 21844854
TI  - Influence of electron density spatial distribution and X-ray beam quality during
      CT simulation on dose calculation accuracy.
AB  - Impact of the various kVp settings used during computed tomography (CT)
      simulation that provides data for heterogeneity corrected dose distribution
      calculations in patients undergoing external beam radiotherapy with either high
      energy photon or electron beams have been investigated. The change of the
      Hounsfield Unit (HU) values due to the influence of kVp settings and geometrical
      distribution of various tissue substitute materials has also been studied. The
      impact of various kVp settings and electron density (ED) distribution on the
      accuracy of dose calculation in high-energy photon beams was found to be well
      within 2%. In the case of dose distributions obtained with a commercially
      available Monte Carlo dose calculation algorithm for electron beams, differences
      of more than 10% were observed for different geometrical setups and kVp settings.
      Dose differences for the electron beams are relatively small at shallow depths
      but increase with depth around lower isodose values.

PMID- 21844855
TI  - Calculation of exit dose for conformal and dynamically-wedged fields, based on
      water-equivalent path length measured with an amorphous silicon electronic portal
      imaging device.
AB  - In this study, we use the quadratic calibration method (QCM), in which an EPID
      image is converted into a matrix of equivalent path lengths (EPLs) and,
      therefore, exit doses, so as to model doses in conformal and enhanced dynamic
      wedge (EDW) fields. The QCM involves acquiring series of EPID images at a
      reference field size for different thicknesses of homogeneous solid water blocks.
      From these, a set of coefficients is established that is used to compute the EPL
      of any other irradiated material. To determine the EPL, the irradiated area must
      be known in order to establish the appropriate scatter correction. A method was
      devised for the automatic calculation of areas from the EPID image that
      facilitated the calculation of EPL for any field and exit dose. For EDW fields,
      the fitting coefficients were modified by utilizing the linac manufacturer's
      golden segmented treatment tables (GSTT) methodology and MU fraction model. The
      nonlinear response of the EPL with lower monitor units (MUs) was investigated and
      slight modification of the algorithm performed to account for this. The method
      permits 2D dose distributions at the exit of phantom or patient to be generated
      by relating the EPL with an appropriate depth dose table. The results indicate
      that the inclusion of MU correction improved the EPL determination. The
      irradiated field areas can be accurately determined from EPID images to within +/
      1% uncertainty. Cross-plane profiles and 2D dose distributions of EPID predicted
      doses were compared with those calculated with the Eclipse treatment planning
      system (TPS) and those measured directly with MapCHECK 2 device. Comparison of
      the 2D EPID dose maps to those from TPS and MapCHECK shows that more than 90% of
      all points passed the gamma index acceptance criteria of 3% dose difference and 3
      mm distance to agreement (DTA), for both conformal and EDW study cases. We
      conclude that the EPID QCM is an accurate and convenient method for in vivo
      dosimetry and may, therefore, complement existing techniques.

PMID- 21844856
TI  - Stability of serrated gold coil markers in prostate localization.
AB  - We investigated the stability of serrated gold coils (Visicoil) implanted within
      the prostate glands of patients undergoing definitive external beam radiotherapy
      for prostate cancer. Radiopaque Visicoils of diameter 0.75 mm and median length 3
      cm (range 2-4 cm) were implanted, one into each lobe of the prostate glands of 30
      patients planned for external beam treatment. The coils were visualized on CT
      simulation and again after 25 fractions of treatment (5 WK). Data from 30
      patients were studied, of whom 19 also received androgen ablation therapy. The
      average change in the distance between the two coils over five weeks of treatment
      was 0.8mm (+/- 0.6 mm), with a maximum of 2.5 mm in one patient. Average residual
      errors (standard deviations) for the positions of individual coil segments after
      five weeks of therapy were only 0.7 mm LAT, 0.6 mm AP, and 0.4 mm SI. The average
      change in distance between the coils over five weeks compared favorably with
      published data regarding marker seed stability. Overall, less than a 2 mm margin
      (i.e., 2 standard deviations) would adequately compensate for positioning
      uncertainty of the coils in more than 95% of cases.

PMID- 21844857
TI  - Characterization of linear accelerator X-ray source size using a laminated beam
      spot camera.
AB  - A laminated beam-spot camera of length 20 cm and effective cross-sectional area
      2.5 cm * 3 cm was designed and constructed for the measurement of X-ray beam-spot
      sizes on different models of Siemens accelerators. With the accelerator gantry at
      180 degrees  and camera positioned on an accessory tray holder, an XV film placed
      in contact with the camera at the distal end of it detected those X-rays that
      were transmitted through the camera. The FWHM of the detected X-ray intensity
      profile in the gun-target (G-T) direction or the orthogonal A-B direction was
      used as a measure of the beam-spot size in that direction. Siemens Mevatron MXEs
      exhibited a beam-spot size of 1.7 +/- 0.2 mm in both the in-plane and cross-plane
      directions for 6 MV photon beams. The beam-spot size observed for a Mevatron MDX
      2 was larger by up to 1 mm, and also was different for the in-plane and cross
      plane directions. For Siemens PRIMUS accelerators, the beam-spot size in the in
      plane direction was found to fall in the range 2.0-2.2 +/- 0.2 mm, whereas the
      beam-spot size in the cross-plane direction fell within 1.7-1.9 +/- 0.2 mm for 6,
      10, and 18 MV photon beams. Assessment of long-term stability of the beam-spot
      size shows the spot size remains fairly stable over time.

PMID- 21844858
TI  - Dosimetric effects of manual cone-beam CT (CBCT) matching for spinal
      radiosurgery: our experience.
AB  - Radiosurgical treatment of cranial or extracranial targets demands accurate
      positioning of the isocenter at the beam and table isocenter, and immobilization
      of the target during treatment. For spinal radiosurgery, the standard approach
      involves matching of cone-beam CT (CBCT) in-room images with the planning CT
      (pCT) to determine translation and yaw corrections. The purpose of this study was
      to assess the accuracy of these techniques compared to advanced automatching
      using mutual information metrics, with consideration given to volume of interest
      (VOI) and optimizing translations and rotations in all axes. The dosimetric
      consequences of our current standard matching techniques were also evaluated. Ten
      consecutive spinal radiosurgery patients treated in the last year were subjected
      to analysis. For purposes of this analysis, the automatch using mutual
      information and a VOI was considered to create "the true isocenter" for
      positioning the patients. Review of the imaging from this automatch confirmed
      perfect superimposition of the two datasets within the VOI. Matching the CBCT to
      the pCT using the automatch allowed assessment of the rotations which had been
      previously ignored. Recalculation of the dose volume histogram was undertaken for
      each patient, assuming displacement of the true isocenter to the treated
      isocenter. Comparisons between the delivered doses and the intended doses were
      made. The mean absolute lateral/vertical/longitudinal translations and vector
      displacement between the manual CBCT-pCT matching isocenter and the true
      isocenter were 0.13, -0.05, and -0.39 mm, with a minimum and maximum individual
      pixel vector shift of 3.2 and 8.94 mm. The mean pitch, yaw, and roll correction
      for automatch was -0.30 degrees , 0.25 degrees , and 0.97 degrees  with a maximum
      of 1.65 degrees , 2.92 degrees , and 1.43 degrees . Four of ten patients had a
      significant change in the coverage of the tumor due to lack of correction of
      translational and rotational errors. The largest errors were observed in patients
      with small and irregular target volumes. Our initial results show that precise
      positioning for spinal radiosurgery cannot be accomplished with manual pCT-CBCT
      matching without a clinical strategy to compensate for rotations. In the absence
      of this, significant underdosing of the tumor may occur.

PMID- 21844859
TI  - Characterization of dose impact on IMRT and VMAT from couch attenuation for two
      Varian couches.
AB  - In intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc
      therapy (VMAT), the use of posterior oblique beams has become common. Beam
      attenuation by the treatment couch is not negligible when the couch is in the
      beam portal. In this study, we established the relationship of relative dose vs.
      beam angle for two Varian 21EX linacs, one equipped with the Exact couch
      (standard couch) with sliding side support rails, and the other equipped with the
      Exact image-guided radiation therapy (IGRT) carbon fiber couch. Measurements were
      performed using an ion chamber placed at the center of an acrylic cylindrical
      phantom positioned at the linac isocenter for 6 MV and 18 MV photon beams.
      Measurements were performed at three different field sizes (3 * 3, 5 * 5, and 10
      * 10 cm2), and were repeated with the phantom positioned at different
      longitudinal locations on the couches. To evaluate beam attenuation by the
      standard couch in a clinical setting, two test IMRT plans and two test VMAT plans
      on the standard couch were delivered. The plans were generated with the sliding
      rails at the "in" position and delivered with the rails at both "in" and "out"
      positions. The dose difference to the ion chamber was determined. For oblique
      fields with 6 MV photons, the standard couch attenuated the radiation beam by up
      to 26.8%, while the carbon fiber IGRT couch attenuated the beam by up to 4.1%. In
      the clinical evaluation, the highest dose difference between rails set at the
      "in" and "out" positions was 2.6% in the IMRT case and 2.1% in the VMAT case. The
      magnitude of potential dose difference has been quantified and could be used for
      a quick estimation of dose difference due to couch attenuation in IMRT and VMAT.

PMID- 21844860
TI  - Physical and dosimetric characteristic of high-definition multileaf collimator
      (HDMLC) for SRS and IMRT.
AB  - Physical and dosimetric characteristics of HDMLC were studied for SRS6, 6, and 10
      MV X-rays from Novalis Tx. This in-built tertiary collimator consists of 60 pairs
      (32 * 0.25 cm; 26 * 0.5 cm and 2 * 0.7 cm) of leaves. Properties of HDMLC studied
      included alignment, readout and radiation field congruence, radiation penumbra,
      accuracy and reproducibility of leaf position and gap width, static and dynamic
      leaf shift, tongue-and-groove effect, leaf transmission and leakage, leaf travel
      speed, and delivery of dynamic conformal arc and IMRT. All tests were performed
      using a calibrated ionization chamber, film dosimetry and DynaLog file analysis.
      Alignment of leaves with isocenter plane was better than 0.03 cm at all gantry
      and collimator positions. The congruence of HDMLC readout and radiation field
      agreed to within +/- 0.03 cm for filed sizes ranging from 1 * 1 to 20 * 20 cm2.
      Mean 80% to 20% penumbra width parallel (perpendicular) to leaf motion was 0.24
      +/- 0.05 (0.21 +/- 0.02) cm, 0.37 +/- 0.12 (0.29 +/- 0.07) cm, and 0.51 +/- 0.13
      (0.43+/- 0.07) cm for SRS6, 6, and 10 MV X-rays, respectively. Circular field
      penumbra was comparable to corresponding square field. Average penumbra of 1 * 20
      cm2 field was effectively constant over off-axis positions of up to 12 cm with
      mean value of 0.16 (+/- 0.01) cm at 1.5 cm depth and 0.38 (+/- 0.04) cm at 10 cm
      depth. Minimum and maximum effective penumbra along the straight diagonal edge of
      irregular fields increased from 0.3 and 0.32 cm at 70 degrees  steep angle to
      0.35 and 0.56 cm at 20 degrees  steep angle. Modified Picket Fence test showed
      average FWHM of 0.18 cm and peak-to-peak distance of 1.99 cm for 0.1 cm band and
      2 cm interband separation. Dynamic multileaf collimation (DMLC) output factor
      remained within +/- 1% for 6 MV and +/- 0.5% for 10 MV X-rays at all gantry
      positions, and was reproducible within +/- 0.5% over a period of 14 months. The
      static leaf shift was 0.03 cm for all energies, while dynamic leaf shift was
      0.044 cm for 10 MV and 0.039 cm for both SRS6 and 6 MV X-rays. The dose
      depression and corresponding tongue-and-groove size were 24% and 0.17 cm for 6 MV
      and 19% and 0.20 cm for 10 MV X-rays. Average transmission through HDMLC was
      1.09%, 1.14% and 1.34% for SRS6, 6 and 10 MV X-rays. Analysis of DynaLog files
      for leaf speed test in arc dynamic mode, delivery test of dynamic conformal arc,
      and step-and-shoot and sliding window IMRT showed at least 95% or more of the
      error counts had misplacements < 0.2 cm, with maximum root mean square (RMS)
      error value calculated at 0.13cm. Accurate and reproducible leaf position and gap
      width, and less leakage and small consistent penumbra over the fields demonstrate
      HDMLC suitable for high-dose resolution SRS and IMRT.

PMID- 21844861
TI  - Impact of the vaginal applicator and dummy pellets on the dosimetry parameters of
      Cs-137 brachytherapy source.
AB  - In this study, dose rate distribution around a spherical 137Cs pellet source,
      from a low-dose-rate (LDR) Selectron remote afterloading system used in
      gynecological brachytherapy, has been determined using experimental and Monte
      Carlo simulation techniques. Monte Carlo simulations were performed using MCNP4C
      code, for a single pellet source in water medium and Plexiglas, and measurements
      were performed in Plexiglas phantom material using LiF TLD chips. Absolute dose
      rate distribution and the dosimetric parameters, such as dose rate constant,
      radial dose functions, and anisotropy functions, were obtained for a single
      pellet source. In order to investigate the effect of the applicator and
      surrounding pellets on dosimetric parameters of the source, the simulations were
      repeated for six different arrangements with a single active source and five non
      active pellets inside central metallic tubing of a vaginal cylindrical
      applicator. In commercial treatment planning systems (TPS), the attenuation
      effects of the applicator and inactive spacers on total dose are neglected. The
      results indicate that this effect could lead to overestimation of the calculated
      F(r,theta), by up to 7% along the longitudinal axis of the applicator, especially
      beyond the applicator tip. According to the results obtained in this study, in a
      real situation in treatment of patients using cylindrical vaginal applicator and
      using several active pellets, there will be a large discrepancy between the
      result of superposition and Monte Carlo simulations.

PMID- 21844862
TI  - Detection of patient setup errors with a portal image - DRR registration software
      application.
AB  - The purpose of this study was to evaluate a custom portal image - digitally
      reconstructed radiograph (DRR) registration software application. The software
      works by transforming the portal image into the coordinate space of the DRR image
      using three control points placed on each image by the user, and displaying the
      fused image. In order to test statistically that the software actually improves
      setup error estimation, an intra- and interobserver phantom study was performed.
      Portal images of anthropomorphic thoracic and pelvis phantoms with virtually
      placed irradiation fields at known setup errors were prepared. A group of five
      doctors was first asked to estimate the setup errors by examining the portal and
      DRR image side-by-side, not using the software. A second group of four
      technicians then estimated the same set of images using the registration
      software. These two groups of human subjects were then compared with an auto
      registration feature of the software, which is based on the mutual information
      between the portal and DRR images. For the thoracic case, the average distance
      between the actual setup error and the estimated error was 4.3 +/- 3.0 mm for
      doctors using the side-by-side method, 2.1 +/- 2.4 mm for technicians using the
      registration method, and 0.8 +/- 0.4mm for the automatic algorithm. For the
      pelvis case, the average distance between the actual setup error and estimated
      error was 2.0 +/- 0.5 mm for the doctors using the side-by-side method, 2.5 +/-
      0.4 mm for technicians using the registration method, and 2.0 +/- 1.0 mm for the
      automatic algorithm. The ability of humans to estimate offset values improved
      statistically using our software for the chest phantom that we tested. Setup
      error estimation was further improved using our automatic error estimation
      algorithm. Estimations were not statistically different for the pelvis case.
      Consistency improved using the software for both the chest and pelvis phantoms.
      We also tested the automatic algorithm with a database of over 5,000 clinical
      cases from our hospital. The algorithm performed well for head and breast but
      performed poorly for pelvis cases, probably due to lack of contrast in the
      megavoltage portal image. The software incorporates an original algorithm to fuse
      portal and DRR images, which we describe in detail. The offset optimization
      algorithm used in the automatic mode of operation is also unique, and may be
      useful if the contrast of the portal images can be improved.

PMID- 21844863
TI  - Evaluation of integrated respiratory gating systems on a Novalis Tx system.
AB  - The purpose of this study was to investigate the accuracy of motion tracking and
      radiation delivery control of integrated gating systems on a Novalis Tx system.
      The study was performed on a Novalis Tx system, which is equipped with Varian
      Real-time Position Management (RPM) system, and BrainLAB ExacTrac gating systems.
      In this study, the two systems were assessed on accuracy of both motion tracking
      and radiation delivery control. To evaluate motion tracking, two artificial
      motion profiles and five patients' respiratory profiles were used. The motion
      trajectories acquired by the two gating systems were compared against the
      references. To assess radiation delivery control, time delays were measured using
      a single-exposure method. More specifically, radiation is delivered with a 4 mm
      diameter cone within the phase range of 10%-45% for the BrainLAB ExacTrac system,
      and within the phase range of 0%-25% for the Varian RPM system during expiration,
      each for three times. Radiochromic films were used to record the radiation
      exposures and to calculate the time delays. In the work, the discrepancies were
      quantified using the parameters of mean and standard deviation (SD). Pearson's
      product-moment correlational analysis was used to test correlation of the data,
      which is quantified using a parameter of r. The trajectory profiles acquired by
      the gating systems show good agreement with those reference profiles. A
      quantitative analysis shows that the average mean discrepancies between BrainLAB
      ExacTrac system and known references are 1.5 mm and 1.9 mm for artificial and
      patient profiles, with the maximum motion amplitude of 28.0 mm. As for the Varian
      RPM system, the corresponding average mean discrepancies are 1.1 mm and 1.7 mm
      for artificial and patient profiles. With the proposed single-exposure method,
      the time delays are found to be 0.20 +/- 0.03 seconds and 0.09 +/- 0.01 seconds
      for BrainLAB ExacTrac and Varian RPM systems, respectively. The results indicate
      the systems can track motion and control radiation delivery with reasonable
      accuracy. The proposed single-exposure method has been demonstrated to be
      feasible in measuring time delay efficiently.

PMID- 21844864
TI  - Evaluation of tomotherapy MVCT image enhancement program for tumor volume
      delineation.
AB  - The aims of this study were to investigate the variability between physicians in
      delineation of head and neck tumors on original tomotherapy megavoltage CT (MVCT)
      studies and corresponding software enhanced MVCT images, and to establish an
      optimal approach for evaluation of image improvement. Five physicians contoured
      the gross tumor volume (GTV) for three head and neck cancer patients on 34
      original and enhanced MVCT studies. Variation between original and enhanced MVCT
      studies was quantified by DICE coefficient and the coefficient of variance. Based
      on volume of agreement between physicians, higher correlation in terms of average
      DICE coefficients was observed in GTV delineation for enhanced MVCT for patients
      1, 2, and 3 by 15%, 3%, and 7%, respectively, while delineation variance among
      physicians was reduced using enhanced MVCT for 12 of 17 weekly image studies.
      Enhanced MVCT provides advantages in reduction of variance among physicians in
      delineation of the GTV. Agreement on contouring by the same physician on both
      original and enhanced MVCT was equally high.

PMID- 21844865
TI  - Individualized margins for prostate patients using a wireless localization and
      tracking system.
AB  - This study investigates the dosimetric benefits of designing patient-specific
      margins for prostate cancer patients based on 4D localization and tracking. Ten
      prostate patients, each implanted with three radiofrequency transponders, were
      localized and tracked for 40 fractions. "Conventional margin" (CM) planning
      target volumes (PTV) and PTVs resulting from uniform margins of 5 mm (5M) and 7
      mm (7M) were explored. Through retrospective review of each patient's tracking
      data, an individualized margin (IM) design for each patient was determined. IMRT
      treatment plans with identical constraints were generated for all four margin
      strategies and compared. The IM plans generally created the smallest PTV volumes.
      For similar PTV coverage, the IM plans had a lower mean bladder (rectal) dose by
      an average of 3.9% (2.5%), 8.5% (5.7%) and 16.2 % (9.8%) compared to 5M, 7M and
      CM plans, respectively. The IM plan had the lowest gEUD value of 23.8 Gy for
      bladder, compared to 35.1, 28.4 and 25.7, for CM, 7M and 5M, respectively.
      Likewise, the IM plan had the lowest NTCP value for rectum of 0.04, compared to
      0.07, 0.06 and 0.05 for CM, 7M and 5M, respectively. Individualized margins can
      lead to significantly reduced PTV volumes and critical structure doses, while
      still ensuring a minimum delivered CTV dose equal to 95% of the prescribed dose.

PMID- 21844866
TI  - Maximum kinetic energy considerations in proton stereotactic radiosurgery.
AB  - The purpose of this study was to determine the maximum proton kinetic energy
      required to treat a given percentage of patients eligible for stereotactic
      radiosurgery (SRS) with coplanar arc-based proton therapy, contingent upon the
      number and location of gantry angles used. Treatment plans from 100 consecutive
      patients treated with SRS at the University of Wisconsin Carbone Cancer Center
      between June of 2007 and March of 2010 were analyzed. For each target volume
      within each patient, in-house software was used to place proton pencil beam spots
      over the distal surface of the target volume from 51 equally-spaced gantry angles
      of up to 360 degrees . For each beam spot, the radiological path length from the
      surface of the patient to the distal boundary of the target was then calculated
      along a ray from the gantry location to the location of the beam spot. This data
      was used to generate a maximum proton energy requirement for each patient as a
      function of the arc length that would be spanned by the gantry angles used in a
      given treatment. If only a single treatment angle is required, 100% of the
      patients included in the study could be treated by a proton beam with a maximum
      kinetic energy of 118 MeV. As the length of the treatment arc is increased to 90
      degrees , 180 degrees , 270 degrees , and 360 degrees , the maximum energy
      requirement increases to 127, 145, 156, and 179 MeV, respectively. A very high
      percentage of SRS patients could be treated at relatively low proton energies if
      the gantry angles used in the treatment plan do not span a large treatment arc.
      Maximum proton kinetic energy requirements increase linearly with size of the
      treatment arc.

PMID- 21844867
TI  - Feasibility study of performing IGRT system daily QA using a commercial QA
      device.
AB  - The purpose of this study was to investigate the feasibility of using a single QA
      device for comprehensive, efficient daily QA of a linear accelerator (Linac) and
      three image-guided stereotactic positioning systems (IGSPSs). The Sun Nuclear
      Daily QA 3 (DQA3) device was used to perform daily dosimetry and mechanical
      accuracy tests for an Elekta Linac, as well as daily image geometric and
      isocenter coincidence accuracy tests for three IGSPSs: the AlignRT surface
      imaging system; the frameless SonArray optical tracking System (FSA) and the
      Elekta kV CBCT. The DQA3 can also be used for couch positioning, repositioning,
      and rotational tests during the monthly QA. Based on phantom imaging, the Linac
      coordinate system determined using AlignRT was within 0.7 mm/0.6 degrees  of that
      of the CBCT system. The difference is attributable to the different calibration
      methods that are utilized for these two systems. The laser alignment was within
      0.5 mm of the isocenter location determined with the three IGSPSs. The ODI
      constancy was +/- 0.5 mm. For gantry and table angles of 0 degrees , the mean
      isocenter displacement vectors determined using the three systems were within 0.7
      mm and 0.6 degrees  of one another. Isocenter rotational offsets measured with
      the systems were all <= 0.5 degrees . For photon and electron beams tested over a
      period of eight months, the output was verified to remain within 2%, energy
      variations were within 2%, and the symmetry and flatness were within 1%. The
      field size and light-radiation coincidence were within 1mm +/- 1 mm. For
      dosimetry reproducibility, the standard deviation was within 0.2% for all tests
      and all energies, except for photon energy variation which was 0.6%. The total
      measurement time for all tasks took less than 15 minutes per QA session compared
      to 40 minutes with our previous procedure, which utilized an individual QA device
      for each IGSPS. The DQA3 can be used for accurate and efficient Linac and IGSPS
      daily QA. It shortens QA device setup time, eliminates errors introduced by
      changing phantoms to perform different tests, and streamlines the task of
      performing dosimetric checks.

PMID- 21844869
TI  - Claudin-4 overexpression is associated with epigenetic derepression in gastric
      carcinoma.
AB  - The tight junction (TJ) protein claudin-4 is aberrantly upregulated in gastric
      cancer, but its clinical significance and the molecular mechanisms underlying
      claudin-4 overexpression in gastric cancer remain unclear. Here, we investigated
      its roles and epigenetic mechanisms regulating CLDN4 expression in gastric
      cancer. We show that increased membranous expression of claudin-4 in gastric
      carcinoma is associated with better patient prognosis, whereas cytoplasmic
      claudin-4 expression did not show a significant association with prognosis.
      Consistent with the correlation of increased membranous claudin-4 with favorable
      clinicopathological factors, claudin-4 overexpression inhibited the migration and
      invasion of gastric cancer cells; in contrast, it did not affect cell growth.
      Claudin-4 expression also increased the barrier function of TJs. Claudin-4
      upregulation was strongly correlated with DNA hypomethylation in both gastric
      tissues and gastric cancer cells. Moreover, CLDN4 expression was repressed in
      normal gastric tissues in association with bivalent histone modifications, and
      loss of repressive histone methylations and gain of active histone modifications
      were associated with CLDN4 overexpression in gastric cancer cells. Interestingly,
      CLDN4 repression could be markedly derepressed by combined treatments that
      simultaneously target both histone modifications and DNA demethylation in CLDN4
      hypermethylated cells, whereas concomitant changes in histone methylations and
      acetylations are required for CLDN4 induction in CLDN4-repressed cells with low
      DNA methylation. Taken together, this study reveals that membranous claudin-4
      expression is associated with gastric cancer progression and that it is an
      independent positive prognosis marker in gastric carcinoma. Furthermore, our
      findings suggest that epigenetic derepression may be a possible mechanism
      underlying CLDN4 overexpression in gastric cancer and that claudin-4 may have
      potential as a promising target for the treatment of gastric cancer.

PMID- 21844870
TI  - Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional
      heteromers with the dopamine D2S receptor in the brain.
AB  - Polymorphic variants of the dopamine D(4) receptor have been consistently
      associated with attention-deficit hyperactivity disorder (ADHD). However, the
      functional significance of the risk polymorphism (variable number of tandem
      repeats in exon 3) is still unclear. Here, we show that whereas the most frequent
      4-repeat (D(4.4)) and the 2-repeat (D(4.2)) variants form functional heteromers
      with the short isoform of the dopamine D(2) receptor (D(2S)), the 7-repeat risk
      allele (D(4.7)) does not. D(2) receptor activation in the D(2S)-D(4) receptor
      heteromer potentiates D(4) receptor-mediated MAPK signaling in transfected cells
      and in the striatum, which did not occur in cells expressing D(4.7) or in the
      striatum of knockin mutant mice carrying the 7 repeats of the human D(4.7) in the
      third intracellular loop of the D(4) receptor. In the striatum, D(4) receptors
      are localized in corticostriatal glutamatergic terminals, where they selectively
      modulate glutamatergic neurotransmission by interacting with D(2S) receptors.
      This interaction shows the same qualitative characteristics than the D(2S)-D(4)
      receptor heteromer-mediated mitogen-activated protein kinase (MAPK) signaling and
      D(2S) receptor activation potentiates D(4) receptor-mediated inhibition of
      striatal glutamate release. It is therefore postulated that dysfunctional D(2S)
      D(4.7) heteromers may impair presynaptic dopaminergic control of corticostriatal
      glutamatergic neurotransmission and explain functional deficits associated with
      ADHD.

PMID- 21844871
TI  - Endogenous knockdown of survivin improves chemotherapeutic response in ALL
      models.
AB  - Although the cure rate of newly diagnosed acute lymphoblastic leukemia (ALL) has
      improved over the past four decades, the outcome for patients who relapse remains
      poor. New therapies are needed for these patients. Our previous global gene
      expression analysis in a series of paired diagnosis-relapse pediatric patient
      samples revealed that the antiapoptotic gene survivin was consistently
      upregulated upon disease relapse. In this study, we demonstrate a link between
      survivin expression and drug resistance and test the efficacy of a novel
      antisense agent in promoting apoptosis when combined with chemotherapy. Gene
      silencing experiments targeting survivin mRNA using either short-hairpin RNA
      (shRNA) or a locked antisense oligonucleotide (LNA-ON) specifically reduced gene
      expression and induced apoptosis in leukemia cell lines. When used in combination
      with chemotherapy, the survivin shRNA and LNA-ON potentiated the chemotherapeutic
      antileukemia effect. Moreover, in a mouse primary xenograft model of relapse ALL,
      the survivin LNA-ON decreased survivin expression in a subset of animals, and
      produced a statistically significant decrease in tumor progression. Taken
      together, these findings suggest that targeting endogenous levels of survivin
      mRNA by LNA-ON methods may augment the response to standard chemotherapy by
      sensitizing otherwise resistant tumor cells to chemotherapy.

PMID- 21844872
TI  - Evolving treatment strategies for patients newly diagnosed with chronic myeloid
      leukemia: the role of second-generation BCR-ABL inhibitors as first-line therapy.
AB  - In patients with chronic myeloid leukemia (CML), disease in the initial chronic
      phase (CP) and subsequent progression are driven by the oncogenic activity of the
      BCR-ABL fusion kinase. Imatinib, a tyrosine kinase inhibitor of BCR-ABL, has been
      the mainstay of first-line therapy for CML for 10 years. Although patients with
      CML-CP respond well to imatinib, those who have delayed reductions in leukemic
      burden during imatinib therapy, such as not achieving a complete cytogenetic
      response (CCyR) by 12 months, have an increased risk of disease progression. It
      has been recognized, with 8 years of observation, that patients who achieve an
      early major molecular response (MMR) on imatinib have a very low probability of
      disease progression. Recent randomized phase 3 trials have shown that first-line
      treatment with dasatinib or nilotinib-more potent BCR-ABL inhibitors-results in
      significantly higher rates and more rapid achievement of CCyR and MMR in
      comparison with standard-dose imatinib. These trials suggest that CML treatment
      can be improved with more potent BCR-ABL inhibition during initial therapy, but
      further follow-up is needed to confirm that the improved response rates with
      dasatinib and nilotinib are maintained long term.

PMID- 21844873
TI  - Persistence of mutant isocitrate dehydrogenase in patients with acute myeloid
      leukemia in remission.

PMID- 21844874
TI  - KIR2DS1 genotype predicts for complete cytogenetic response and survival in newly
      diagnosed chronic myeloid leukemia patients treated with imatinib.
AB  - Natural killer (NK) cells are expanded in chronic myeloid leukemia (CML) patients
      on tyrosine kinase inhibitors (TKI) and exert cytotoxicity. The inherited
      repertoire of killer immunoglobulin-like receptors (KIR) may influence response
      to TKI. We investigated the impact of KIR-genotype on outcome in 166 chronic
      phase CML patients on first-line imatinib treatment. We validated our findings in
      an independent patient group. On multivariate analysis, KIR2DS1 genotype
      (RR=1.51, P=0.03) and Sokal risk score (low-risk RR=1, intermediate-risk RR=1.53,
      P=0.04, high-risk RR=1.69, P=0.034) were the only independent predictors for
      failure to achieve complete cytogenetic response (CCyR). Furthermore, KIR2DS1 was
      the only factor predicting shorter progression-free (PFS) (RR=3.1, P=0.03) and
      overall survival (OS) (RR=2.6, P=0.04). The association between KIR2DS1 and CCyR,
      PFS and OS was validated by KIR genotyping in 174 CML patients on first-line
      imatinib in the UK multi-center SPIRIT-1 trial; in this cohort, KIR2DS1(+)
      patients had significantly lower 2-year probabilities of achieving CCyR (76.9 vs
      87.9%, P=0.003), PFS (85.3 vs 98.1%, P=0.007) and OS (94.4 vs 100%, P=0.015) than
      KIR2DS1(-) patients. The impact of KIR2DS1 on CCyR was greatest when the ligand
      for the corresponding inhibitory receptor, KIR2DL1, was absent (P=0.00006). Our
      data suggest a novel role for KIR-HLA immunogenetics in CML patients on TKI.

PMID- 21844875
TI  - Absence of IL-12Rbeta2 in CD33(+)CD38(+) pediatric acute myeloid leukemia cells
      favours progression in NOD/SCID/IL2RgammaC-deficient mice.
AB  - Childhood acute myeloid leukemia (AML) is a hematological malignancy in which
      tumor burden is continuously replenished by leukemic-initiating cells (ICs),
      which proliferate slowly and are refractory to chemotherapeutic agents. We
      investigated whether interleukin (IL)-12, an immuno-modulatory cytokine with anti
      tumor activity, may target AML blasts (CD45(+)CD33(+)) and populations known to
      contain leukemia ICs (that is, CD34(+)CD38(-), CD33(+)CD38(+) and CD44(+)CD38(-)
      cells). We demonstrate for the first time that: i) AML blasts and their
      CD34(+)CD38(-), CD33(+)CD38(+), CD44(+)CD38(-) subsets express the heterodimeric
      IL-12 receptor (IL-12R), ii) AML cells injected subcutaneously into
      NOD/SCID/Il2rg(-/-) (NSG) mice developed a localized tumor mass containing
      leukemic ICs and blasts that were virtually eliminated by IL-12 treatment, iii)
      AML cells injected intravenously into NSG mice engrafted within the first month
      in the spleen, but not in bone marrow or peripheral blood. At this time, IL-12
      dramatically dampened AML CD45(+)CD33(+), CD34(+)CD38(-), CD33(+)CD38(+) and
      CD44(+)CD38(-) populations, only sparing residual CD33(+)CD38(+) cells that did
      not express IL-12Rbeta2. From 30 to 60 days after the initial inoculum, these IL
      12-unresponsive cells expanded and metastasized in both control and IL-12-treated
      NSG mice. Our data indicate that the absence of IL-12Rbeta2 in pediatric AML
      cells favours leukemia progression in NOD/SCID/IL2Rgammac-deficient mice.

PMID- 21844876
TI  - Taste preferences in association with dietary habits and weight status in
      European children: results from the IDEFICS study.
AB  - BACKGROUND: Increased preference for fat and sugar may have a role in overweight
      and obesity development. However, this effect is likely to vary across different
      food cultures. To date, few studies on this topic have been conducted in children
      and none have employed an international, multi-centre design. OBJECTIVE: To
      document taste preferences for fat and sweet in children from eight European
      countries and to investigate their association with weight status and dietary
      habits. DESIGN: A total of 1696 children aged 6-9 years from survey centres in
      Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary and Spain tasted and
      subsequently chose between a high- versus a low-fat cracker and a natural versus
      a sugar-sweetened apple juice. Children's consumption frequency of fatty and
      sweet foods and demographic variables were obtained from parental-reported
      questionnaires. Weight and height of the children were measured. RESULTS: Fat and
      sweet taste preferences varied substantially across survey centres. Independent
      of survey centre, age, sex, parental education and parental BMI, overweight
      including obesity was positively associated with fat preference and sweet
      preference. Fat preference associations were stronger in girls. Girls, but not
      boys, with a combined preference for fat and sweet had an especially high
      probability of being overweight or obese. Adjusted models with BMI z-score as the
      dependent variable were consistent with results of the analyses with BMI
      categories, but with significant results only for fat preference in girls.
      Frequent consumption of fatty foods was related to fat preference in bivariate
      analyses; however, adjusting for survey centre attenuated the association. Sweet
      preference was not related to consumption of sweet foods, either in crude or in
      adjusted analyses. CONCLUSIONS: Fat and sweet taste preferences are related to
      weight status in European children across regions with varying food cultures.

PMID- 21844877
TI  - Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese
      children.
AB  - OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic
      process and functional polymorphisms in the MMP-9 gene affect MMP-9
      expression/activity, and are associated with cardiovascular diseases. However, no
      study has tested the hypothesis that functional MMP-9 polymorphisms could affect
      MMP-9 levels in obese children. We investigated whether three MMP-9 gene
      polymorphisms (C-1562T (rs3918242), 90(CA)((14-24)) (rs2234681) and Q279R
      (rs17576)), or haplotypes, affect MMP-9 levels in obese children. METHODS: We
      studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue
      inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using
      enzyme-linked immunosorbent assay. RESULTS: We found similar MMP-9 genotypes,
      allelic and haplotypes distributions in the two study groups (P>0.05). However,
      we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or
      the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in
      obese children compared with children with the other genotypes, or with non-obese
      children with the same genotypes (all P<0.05). Moreover, we found lower MMP-9
      levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese
      children carrying the H2 haplotype (which combines the C, H and Q alleles for the
      three polymorphisms, respectively) when compared with obese children carrying the
      other haplotypes, or with non-obese children carrying the same haplotype
      (P<0.05). CONCLUSIONS: Our findings show that MMP-9 genotypes and haplotypes
      affect MMP-9 levels in obese children and adolescents, and suggest that genetic
      factors may modify relevant pathogenetic mechanisms involved in the development
      of cardiovascular complications associated with obesity in childhood.

PMID- 21844878
TI  - Simultaneous postprandial deregulation of the orexigenic endocannabinoid
      anandamide and the anorexigenic peptide YY in obesity.
AB  - BACKGROUND: The endocannabinoid system is a potential pharmacotherapy target for
      obesity. However, the role of this system in human food intake regulation is
      currently unknown. METHODS: To test whether circulating endocannabinoids might
      functionally respond to food intake and verify whether these orexigenic signals
      are deregulated in obesity alongside with anorexigenic ones, we measured plasma
      anandamide (AEA), 2-arachidonoylglycerol (2-AG) and peptide YY (PYY) changes in
      response to a meal in 12 normal-weight and 12 non-diabetic, insulin-resistant
      obese individuals. RESULTS: Both normal-weight and obese subjects had a
      significant preprandial AEA peak. Postprandially, AEA levels significantly
      decreased in normal-weight, whereas no significant changes were observed in obese
      subjects. Similarly, PYY levels significantly increased in normal-weight subjects
      only. No meal-related changes were found for 2-AG. Postprandial AEA and PYY
      changes inversely correlated with waist circumference, and independently
      explained 20.7 and 21.3% of waist variance. Multiple regression analysis showed
      that postprandial AEA and PYY changes explained 34% of waist variance, with 8.2%
      of the variance commonly explained. CONCLUSION: These findings suggest that AEA
      might be a physiological meal initiator in humans and furthermore show that
      postprandially AEA and PYY are concomitantly deregulated in obesity.

PMID- 21844879
TI  - Safety, tolerability and sustained weight loss over 2 years with the once-daily
      human GLP-1 analog, liraglutide.
AB  - OBJECTIVE: Having demonstrated short-term weight loss with liraglutide in this
      group of obese adults, we now evaluate safety/tolerability (primary outcome) and
      long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.
      DESIGN: A randomized, double-blind, placebo-controlled 20-week study with 2-year
      extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year)
      in 19 European clinical research centers. SUBJECTS: A total of 564 adults (n=90
      98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension
      and 268 completed the 2-year trial. Participants received diet (500 kcal deficit
      per day) and exercise counseling during 2-week run-in, before being randomly
      assigned (with a telephone or web-based system) to once-daily subcutaneous
      liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label
      orlistat (120 mg * 3, n=95). After 1 year, liraglutide/placebo recipients
      switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results,
      respectively). The trial ran from January 2007-April 2009 and is registered with
      Clinicaltrials.gov, number NCT00480909. RESULTS: From randomization to year 1,
      liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more
      weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat
      (P?0.0001; intention-to-treat, last-observation-carried-forward). At year 2,
      participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184)
      lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001).
      Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of
      7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by
      15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were
      mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the
      2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%,
      with improvements in blood pressure and lipids. CONCLUSION: Liraglutide is well
      tolerated, sustains weight loss over 2 years and improves cardiovascular risk
      factors.

PMID- 21844881
TI  - An instructive role of donor macrophages in mixed chimeras in the induction of
      recipient CD4(+)Foxp3(+) Treg cells.
AB  - The immune regulatory function of macrophages (Mos) in mixed chimeras has not
      been determined. In the present study, with a multi-lineage B6-to-BALB/c mixed
      chimeric model, we examined the ability of donor-derived splenic Mos in the
      induction of regulatory T cells (Treg). B6 splenic Mos from mixed chimeras
      induced significantly less cell proliferation, more IL-10 and TGF-beta, and less
      IL-2 and IFN-gamma productions of CD4(+) T cells from BALB/c mice than naive B6
      Mos did, whereas they showed similar stimulatory activity to the third part C3H
      CD4(+) T cells. Importantly, highly purified donor F4/80(+)CD11c(-) Mos
      efficiently induced recipient CD4(+)Foxp3(+) Treg cells from CD4(+)CD25(-)Foxp3(
      ) T cells. Furthermore, donor Mos of mixed chimeras produced more IL-10 and less
      IFN-gamma than those of naive mice when cultured with BALB/c but not the third
      party C3H CD4(+) T cells. Induction of recipient CD4(+) Treg cells by donor Mos
      was significantly blocked by anti-IL-10, but not by anti-TGF-beta mAb. Therefore,
      donor Mos have the ability to induce recipient CD4(+)Foxp3(+) Treg cells in a
      donor antigen-specific manner, at least partially, via an IL-10-dependent
      pathway. This study for the first time showed that, in mixed allogeneic chimeras,
      donor Mos could be specifically tolerant to recipients and gained the ability to
      induce recipient but not the third party Foxp3(+) Treg cells. Whether this
      approach is involved in transplant immune tolerance needs to be determined.

PMID- 21844882
TI  - Protection against Nippostrongylus brasiliensis infection in mice is independent
      of GM-CSF.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) is a cytokine with the
      capacity to promote inflammation in a wide variety of infectious and inflammatory
      diseases. These conditions include allergic airway inflammation, which is driven
      by T-helper 2 (Th2) cells. Because of the importance of Th2 cells in parasite
      infections, we have investigated the role of GM-CSF in mice infected with the
      nematode Nippostrongylus brasiliensis. The effect of primary and secondary
      infection was investigated in mice lacking functional genes for GM-CSF (CSF2
      genes) (DeltaGM-CSF mice), and in mice lacking the cytokine receptor common beta
      chain (Deltabeta mice), the latter being unable to signal in response to GM-CSF
      and interleukin (IL)-5. DeltaGM-CSF mice showed no significant defect in parasite
      immunity, measured by larval numbers in the lungs, worm numbers in the intestine
      or egg numbers in the faeces, in either primary or secondary infection. By
      contrast, the Deltabeta mice showed increased parasite burden, with higher
      numbers of lung larvae after secondary infection and higher numbers of intestinal
      worms and faecal eggs after both primary and secondary infection. Unexpectedly,
      there were increased numbers of circulating eosinophils in the DeltaGM-CSF mice,
      associated with significantly reduced larval numbers in the lungs. These results
      indicate that GM-CSF is redundant in protection against N. brasiliensis
      infection, and that the increased susceptibility of Deltabeta mice to infection
      is likely to be attributed to the lack of IL-5 signalling in these mice. The
      results suggest that clinical use of agents that neutralise GM-CSF may not be
      associated with increased risk of parasite infection.

PMID- 21844883
TI  - Return of inactivated whole-virus vaccine for superior efficacy.
AB  - The swine, influenza, H1N1 outbreak in 2009 highlighted the inadequacy of the
      currently used antibody-based vaccine strategies as a preventive measure for
      combating influenza pandemics. The ultimate goal for successful control of newly
      arising influenza outbreaks is to design a single-shot vaccine that will provide
      long-lasting immunity against all strains of influenza A virus. A large amount of
      data from animal studies has indicated that the cross-reactive cytotoxic T (Tc)
      cell response against conserved influenza virus epitopes may be the key immune
      response needed for a universal influenza vaccine. However, decades of research
      have shown that the development of safe T-cell-based vaccines for influenza is
      not an easy task. Here, I discuss the overlooked but potentially highly
      advantageous inactivation method, namely, gamma-ray irradiation, as a mean to
      reach the Holy Grail of influenza vaccinology.

PMID- 21844880
TI  - Growth of Candida albicans hyphae.
AB  - The fungus Candida albicans is often a benign member of the mucosal flora;
      however, it commonly causes mucosal disease with substantial morbidity and in
      vulnerable patients it causes life-threatening bloodstream infections. A striking
      feature of its biology is its ability to grow in yeast, pseudohyphal and hyphal
      forms. The hyphal form has an important role in causing disease by invading
      epithelial cells and causing tissue damage. This Review describes our current
      understanding of the network of signal transduction pathways that monitors
      environmental cues to activate a programme of hypha-specific gene transcription,
      and the molecular processes that drive the highly polarized growth of hyphae.

PMID- 21844884
TI  - Genome-wide meta-analysis identifies variants associated with platinating agent
      susceptibility across populations.
AB  - Platinating agents are used in the treatment of many cancers, yet they can induce
      toxicities and resistance that limit their utility. Using previously published
      and additional world population panels of diverse ancestry totaling 608
      lymphoblastoid cell lines (LCLs), we performed meta-analyses of over 3 million
      single-nucleotide polymorphisms (SNPs) for both carboplatin- and cisplatin
      induced cytotoxicity. The most significant SNP in the carboplatin meta-analysis
      is located in an intron of NBAS (neuroblastoma amplified sequence; P=5.1 * 10(
      7)). The most significant SNP in the cisplatin meta-analysis is upstream of
      KRT16P2 (P=5.8 * 10(-7)). We also show that cisplatin-susceptibility SNPs are
      enriched for carboplatin-susceptibility SNPs. Most of the variants that associate
      with platinum-induced cytotoxicity are polymorphic across multiple world
      populations; therefore, they could be tested in follow-up studies in diverse
      clinical populations. Seven genes previously implicated in platinating agent
      response, including BCL2 (B-cell CLL/lymphoma 2), GSTM1 (glutathione S
      transferase mu 1), GSTT1, ERCC2 and ERCC6, were also implicated in our meta
      analyses.

PMID- 21844885
TI  - Vascular endothelial growth factor polymorphisms and clinical outcome in
      colorectal cancer patients treated with irinotecan-based chemotherapy and
      bevacizumab.
AB  - The aim of the study was to evaluate the association of vascular endothelial
      growth factor (VEGF) genotypes with treatment efficacy in a randomized trial.
      This study compared two chemotherapy regimens (FOLFIRI versus XELIRI) combined
      with bevacizumab, as first-line treatment for metastatic colorectal cancer. DNA
      was extracted from blood samples of 173 patients participating in the trial.
      Genotyping was performed for selected SNPs (VEGF-1154, +936, -634, -2578 and 
      1498). All candidate genotypes were evaluated for associations with overall
      survival (OS), progression-free survival (PFS) and response rate (RR). There were
      no significant differences with respect to the distribution of genotypes in the
      treatment groups. The VEGF-1154 GG genotype was more frequent in patients not
      responding to treatment compared with responders (65.5 versus 39.8%, P = 0.032).
      Furthermore, the VEGF-1154 GG genotype was associated with inferior median OS
      compared with GA (hazards ratio = 1.68; 95% confidence interval: 1.10-2.57; P =
      0.016) or with the alternative genotypes (GA and AA) combined (hazards ratio =
      1.62; 95% confidence interval: 1.09-2.40; P = 0.017). In multivariate analysis,
      the VEGF-1154 GG genotype remained a significant adverse factor for OS. Our
      results support the potential predictive ability of VEGF genotypes in patients
      with metastatic colorectal cancer receiving irinotecan-based chemotherapy plus
      bevacizumab, in terms of RR and OS. However, current results should be validated
      prospectively, in larger cohorts.

PMID- 21844886
TI  - Editor's comments.

PMID- 21844888
TI  - Overcoming the challenges of robot-assisted radical prostatectomy.
AB  - Robot-assisted radical prostatectomy (RARP) is the most commonly performed
      robotic procedure worldwide and is firmly established as a standard treatment
      option for localised prostate cancer. Part of the explanation for the rapid
      uptake of RARP is the reported gentler learning curve compared with the
      challenges of laparoscopic radical prostatectomy (LRP). However, robotic surgery
      is still fraught with potential difficulties and avoiding complications while on
      the steepest part of the learning curve is critical. Furthermore, as surgeons
      progress there is a tendency to take on increasingly complex cases, including
      patients with difficult anatomy and prior surgery, and these cases present a
      unique challenge. Significant intra-abdominal adhesions may be identified
      following open surgery, or dense periprostatic inflammation may be encountered
      following TURP; large prostate gland size and median lobes may alter bladder neck
      anatomy, making difficult subsequent urethro-vesical anastomosis. Even
      experienced robotic surgeons will be challenged by salvage RARP. Approaching
      these problems in a structured manner allows many of the problems to be overcome.
      We discuss some of the specific techniques to deal with these potential
      difficulties and highlight ways to avoid making serious mistakes.

PMID- 21844889
TI  - 18F-fluorocholine for prostate cancer imaging: a systematic review of the
      literature.
AB  - BACKGROUND: Positron emission tomography (PET or combined PET-computed tomography
      (PET/CT)) allows the non-invasive interrogation of metabolic processes using
      radiolabeled probes. Altered choline metabolism has been noted as a
      characteristic of prostate cancer (PCa), and radiolabeled choline and choline
      analogs have been investigated as PET/CT imaging agents for prostate cancer;
      [(18)F]fluoromethyl-dimethyl-2-hydroxyethyl-ammonium ((18)F-FCH) shows particular
      promise as a PCa imaging agent given its favorable physical and pharmacokinetic
      properties. METHODS: We conducted a systematic review of results to date with
      (18)F-FCH. As the tracer was first described by DeGrado in 2001, we limited our
      search from January 2001 to August 2011. RESULTS: In all, 37 studies including
      1244 patients met the inclusion criteria. Studies included those detailing the
      radiosynthesis of (18)F-FCH, preclinical and early clinical dosimetry, and
      biodistribution (n=7); evaluation of local disease (n=6), nodal disease (n=5),
      bone metastases and castrate-resistant disease (n=7), biochemical recurrence
      (n=11), radiotherapy planning (n=7) and sources of false-positive studies (n=2);
      and some studies reported on multiple indications. Potential sources of
      variations in the studies affecting reported performance included case series
      size, variation in extent of disease at imaging (including Gleason grade, and
      PSA), selection of gold standards for comparison and variations in scan
      technique. CONCLUSIONS: On the basis of the review, we suggest potential
      scenarios where this metabolic imaging might be considered for further evaluation
      in clinical trials for guiding PCa management.

PMID- 21844890
TI  - NOPO modulates Egr-induced JNK-independent cell death in Drosophila.
AB  - Tumor necrosis factor (TNF) family ligands play essential roles in regulating a
      variety of cellular processes including proliferation, differentiation and
      survival. Expression of Drosophila TNF ortholog Eiger (Egr) induces JNK-dependent
      cell death, while the roles of caspases in this process remain elusive. To
      further delineate the Egr-triggered cell death pathway, we performed a genetic
      screen to identify dominant modifiers of the Egr-induced cell death phenotype.
      Here we report that Egr elicits a caspase-mediated cell death pathway independent
      of JNK signaling. Furthermore, we show NOPO, the Drosophila ortholog of TRIP
      (TRAF interacting protein) encoding an E3 ubiquitin ligase, modulates Egr-induced
      Caspase-mediated cell death through transcriptional activation of pro-apoptotic
      genes reaper and hid. Finally, we found Bendless and dUEV1a, an ubiquitin
      conjugating E2 enzyme complex, regulates NOPO-triggered cell death. Our results
      indicate that the Ben-dUEV1a complex constitutes a molecular switch that
      bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK
      and caspases respectively.

PMID- 21844891
TI  - A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo.
AB  - Sorting nexins (SNXs) are phosphoinositide-binding proteins implicated in the
      sorting of various membrane proteins in vitro, but the in vivo functions of them
      remain largely unknown. We reported previously that SNX10 is a unique member of
      the SNX family genes in that it has vacuolation activity in cells. We investigate
      the biological function of SNX10 by loss-of-function assay in this study and
      demonstrate that SNX10 is required for the formation of primary cilia in cultured
      cells. In zebrafish, SNX10 is involved in ciliogenesis in the Kupffer's vesicle
      and essential for left-right patterning of visceral organs. Mechanistically,
      SNX10 interacts with V-ATPase complex and targets it to the centrosome where
      ciliogenesis is initiated. Like SNX10, V-ATPase regulates ciliogenesis in vitro
      and in vivo and does so synergistically with SNX10. We further discover that
      SNX10 and V-ATPase regulate the ciliary trafficking of Rab8a, which is a critical
      regulator of ciliary membrane extension. These results identify an SNX10/V-ATPase
      regulated vesicular trafficking pathway that is crucial for ciliogenesis, and
      reveal that SNX10/V-ATPase, through the regulation of cilia formation in various
      organs, play an essential role during early embryonic development.

PMID- 21844892
TI  - Transduction of the Hedgehog signal through the dimerization of Fused and the
      nuclear translocation of Cubitus interruptus.
AB  - The Hedgehog (Hh) family of secreted proteins is essential for development in
      both vertebrates and invertebrates. As one of main morphogens during metazoan
      development, the graded Hh signal is transduced across the plasma membrane by
      Smoothened (Smo) through the differential phosphorylation of its cytoplasmic
      tail, leading to pathway activation and the differential expression of target
      genes. However, how Smo transduces the graded Hh signal via the Costal2
      (Cos2)/Fused (Fu) complex remains poorly understood. Here we present a model of
      the cell response to a Hh gradient by translating Smo phosphorylation information
      to Fu dimerization and Cubitus interruptus (Ci) nuclear localization information.
      Our findings suggest that the phosphorylated C-terminus of Smo recruits the
      Cos2/Fu complex to the membrane through the interaction between Smo and Cos2,
      which further induces Fu dimerization. Dimerized Fu is phosphorylated and
      transduces the Hh signal by phosphorylating Cos2 and Suppressor of Fu (Su(fu)).
      We further show that this process promotes the dissociation of the full-length Ci
      (Ci155) and Cos2 or Su(fu), and results in the translocation of Ci155 into the
      nucleus, activating the expression of target genes.

PMID- 21844893
TI  - Actin regulation during abscission: unexpected roles of Rab35 and endocytic
      transport.

PMID- 21844894
TI  - Defining the nature of human pluripotent stem cell progeny.
AB  - While it is clear that human pluripotent stem cells (hPSCs) can differentiate to
      generate a panoply of various cell types, it is unknown how closely in vitro
      development mirrors that which occurs in vivo. To determine whether human
      embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs)
      make equivalent progeny, and whether either makes cells that are analogous to
      tissue-derived cells, we performed comprehensive transcriptome profiling of
      purified PSC derivatives and their tissue-derived counterparts. Expression
      profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for
      the neural, hepatic, and mesenchymal lineages, and an absence of re-expression
      from exogenous reprogramming factors in hiPSC progeny. However, when compared to
      a tissue-derived counterpart, the progeny of both hESCs and hiPSCs maintained
      expression of a subset of genes normally associated with early mammalian
      development, regardless of the type of cell generated. While pluripotent genes
      (OCT4, SOX2, REX1, and NANOG) appeared to be silenced immediately upon
      differentiation from hPSCs, genes normally unique to early embryos (LIN28A,
      LIN28B, DPPA4, and others) were not fully silenced in hPSC derivatives. These
      data and evidence from expression patterns in early human fetal tissue (3-16
      weeks of development) suggest that the differentiated progeny of hPSCs are
      reflective of very early human development (< 6 weeks). These findings provide
      support for the idea that hPSCs can serve as useful in vitro models of early
      human development, but also raise important issues for disease modeling and the
      clinical application of hPSC derivatives.

PMID- 21844895
TI  - Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and
      dysfunction in mice.
AB  - Recent studies have begun to reveal critical roles of microRNAs (miRNAs) in the
      pathogenesis of cardiac hypertrophy and dysfunction. In this study, we tested
      whether a transforming growth factor-beta (TGF-beta)-regulated miRNA played a
      pivotal role in the development of cardiac hypertrophy and heart failure (HF). We
      observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4
      knockout mice, which developed cardiac hypertrophy. In vitro experiments showed
      that the miR-27b expression could be inhibited by TGF-beta1 and that its
      overexpression promoted hypertrophic cell growth, while the miR-27b suppression
      led to inhibition of the hypertrophic cell growth caused by phenylephrine (PE)
      treatment. Furthermore, the analysis of transgenic mice with cardiomyocyte
      specific overexpression of miR-27b revealed that miR-27b overexpression was
      sufficient to induce cardiac hypertrophy and dysfunction. We validated the
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) as a direct target
      of miR-27b in cardiomyocyte. Consistently, the miR-27b transgenic mice displayed
      significantly lower levels of PPAR-gamma than the control mice. Furthermore, in
      vivo silencing of miR-27b using a specific antagomir in a pressure-overload
      induced mouse model of HF increased cardiac PPAR-gamma expression, attenuated
      cardiac hypertrophy and dysfunction. The results of our study demonstrate that
      TGF-beta1-regulated miR-27b is involved in the regulation of cardiac hypertrophy,
      and validate miR-27b as an efficient therapeutic target for cardiac diseases.

PMID- 21844898
TI  - Experimental arthritis: addressing inflamed joints with peptides.

PMID- 21844896
TI  - Management of pain in multiple sclerosis: a pharmacological approach.
AB  - About half of patients with multiple sclerosis (MS) report pain; treatment for
      pain alone accounts for nearly 30% of the total use of medications for the
      management of all MS-related symptoms. Patients with MS can experience more than
      one type of pain simultaneously and at any point during the disease course, even
      in newly or recently diagnosed cases. Pain in MS can be associated with other
      symptoms, including spasticity, fatigue and mood disorder. Pain sufferers
      experience disruption in daily life activities, work, mood, recreation and
      general enjoyment of life, and report low satisfaction with pain management. Many
      clinical features of pain are often unrecognized by clinicians and are difficult
      for patients to describe. The majority of clinical evidence regarding treatment
      stems from small pilot and open-label studies; therefore, treatment of pain
      associated with MS is often based on anecdotal reports and clinicians'
      experience. The open-label design of the majority of studies, the unavailability
      of large samples and the difficulty of performing placebo-controlled studies
      because of ethical considerations result in insufficient evidence to support or
      refute the effectiveness of pain medications. This Review presents available data
      regarding pharmacological approaches for addressing pain in MS and highlights the
      shortcomings in pain management research.

PMID- 21844899
TI  - Rheumatoid arthritis: which cells produce which cytokines?

PMID- 21844900
TI  - Apoptosis-resistant T cells in SLE: role for the regulatory B subunits of PP2A
      phosphatase.

PMID- 21844897
TI  - Advances in the diagnosis, pathogenesis and treatment of CIDP.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common
      chronic autoimmune neuropathy. Despite clinical challenges in diagnosis-owing in
      part to the existence of disease variants, and different views on how many
      electrophysiological abnormalities are needed to document demyelination-consensus
      criteria seem to have been reached for research or clinical practice. Current
      standard of care involves corticosteroids, intravenous immunoglobulin (IVIg)
      and/or plasmapheresis, which provide short-term benefits. Maintenance therapy
      with IVIg can induce sustained remission, increase quality of life and prevent
      further axonal loss, but caution is needed to avoid overtreatment. Commonly used
      immunosuppressive drugs offer minimal benefit, necessitating the development of
      new therapies for treatment-refractory patients. Advances in our understanding of
      the underlying immunopathology in CIDP have identified new targets for future
      therapeutic efforts, including T cells, B cells, and transmigration and
      transduction molecules. New biomarkers and scoring systems represent emerging
      tools with the potential to predict therapeutic responses and identify patients
      with active disease for enrollment into clinical trials. This Review highlights
      the recent advances in diagnosing CIDP, provides an update on the immunopathology
      including new target antigens, and discusses current treatments, ongoing
      challenges and future therapeutic directions.

PMID- 21844901
TI  - Health policy: reducing radiation exposure time for ureteroscopic procedures.

PMID- 21844902
TI  - Prostate cancer: operate or wait? Nomogram decides.

PMID- 21844903
TI  - Male factor infertility: mutation of sperm defensin causes subfertility.

PMID- 21844904
TI  - Incontinence: should mesh be used to correct anterior vaginal prolapse?

PMID- 21844905
TI  - Bladder cancer: validating the EORTC risk tables in BCG-treated patients.

PMID- 21844906
TI  - Prevention and management of TURP-related hemorrhage.
AB  - Transurethral resection of the prostate (TURP) is the most common surgical
      treatment for benign prostatic hyperplasia (BPH) worldwide, but despite its
      minimally invasive nature, perioperative bleeding remains a common morbidity.
      Anticoagulant and antiplatelet medications are increasingly common in this
      patient population and further contribute to the risk of bleeding and extended
      hospital stay. Preoperative cessation of anticoagulant and antiplatelet drugs is
      recommended but requires risk assessment of thrombotic complications.
      Pharmacologic maneuvers to reduce hemorrhage include perioperative administration
      of 5alpha-reductase inhibitors. Technical considerations include the use of
      hemostatic energy sources such as laser and bipolar technologies. Ultimately, no
      surgical technique is devoid of bleeding risks, and urologists should be aware of
      how best to prevent and treat TURP-related hemorrhage.

PMID- 21844908
TI  - Thyroid function: new guidance for the diagnosis and management of thyroid
      diseases in pregnancy.

PMID- 21844909
TI  - Thyroid cancer: reduced serum VEGF-D levels in metastatic differentiated thyroid
      cancer.

PMID- 21844907
TI  - The G-protein-coupled estrogen receptor GPER in health and disease.
AB  - Estrogens mediate profound effects throughout the body and regulate physiological
      and pathological processes in both women and men. The low prevalence of many
      diseases in premenopausal women is attributed to the presence of 17beta
      estradiol, the predominant and most potent endogenous estrogen. In addition to
      endogenous estrogens, several man-made and plant-derived molecules, such as
      bisphenol A and genistein, also exhibit estrogenic activity. Traditionally, the
      actions of 17beta-estradiol are ascribed to two nuclear estrogen receptors (ERs),
      ERalpha and ERbeta, which function as ligand-activated transcription factors.
      However, 17beta-estradiol also mediates rapid signaling events via pathways that
      involve transmembrane ERs, such as G-protein-coupled ER 1 (GPER; formerly known
      as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling
      and transcriptional regulation. With the discovery of GPER-selective ligands that
      can selectively modulate GPER function in vitro and in preclinical studies and
      with the use of Gper knockout mice, many more potential roles for GPER are being
      elucidated. This Review highlights the physiological roles of GPER in the
      reproductive, nervous, endocrine, immune and cardiovascular systems, as well as
      its pathological roles in a diverse array of disorders including cancer, for
      which GPER is emerging as a novel therapeutic target and prognostic indicator.

PMID- 21844911
TI  - Spondylodiscitis in a patient on chronic hemodialysis.
AB  - BACKGROUND: A 73-year-old man on hemodialysis with a tunneled central venous
      catheter presented to the emergency room with a fever and severe back pain.
      INVESTIGATIONS: Physical examination, laboratory investigations, chest
      radiography, lumbar spine radiography, renal ultrasound, lumbosacral spine MRI
      and transthoracic echocardiography. DIAGNOSIS: Spondylodiscitis as a result of
      methicillin-sensitive Staphylococcus aureus bacteremia. MANAGEMENT: Antibiotic
      therapy with intravenous cefazolin for 6 weeks and oral minocycline for 2 weeks.

PMID- 21844912
TI  - Targeted therapies: An important piece of the localized prostate cancer puzzle?

PMID- 21844910
TI  - The intestinal microbiota and chronic disorders of the gut.
AB  - Mucosal surfaces of the gut are colonized by large numbers of heterogeneous
      bacteria that contribute to intestinal health and disease. In genetically
      susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut
      flora contributes to alterations in the mucosa and local immune system leading to
      gastrointestinal disease. These diseases include enteric infections, such as
      Clostridium difficile infection, small intestinal bacterial overgrowth,
      functional gastrointestinal disorders (including IBS), IBD and colorectal cancer.
      Prebiotics, probiotics and synbiotics (a combination of prebiotics and
      probiotics) have the capacity to reverse pathologic changes in gut flora and
      local immunity. Intestinal health and disease need to be thoroughly characterized
      to understand the interplay between the indigenous microbiota, the immune system
      and genetic host factors. This Review provides a broad overview of the importance
      of the intestinal microbiota in chronic disorders of the gut.

PMID- 21844913
TI  - Targeted therapies: Risk of heart failure with sunitinib.

PMID- 21844914
TI  - Prevention: Small reductions in risk factors equal big savings in health-care
      costs.

PMID- 21844915
TI  - Acute coronary syndromes: APPRAISE-2 results published.

PMID- 21844916
TI  - Antiplatelet therapy: Surgery should not interrupt treatment.

PMID- 21844917
TI  - Hypertension: Baroreflex activation therapy lowers BP.

PMID- 21844918
TI  - The road to biological pacing.
AB  - The field of biological pacing is entering its second decade of active
      investigation. The inception of this area of study was serendipitous, deriving
      largely from observations made by several teams of investigators, whose common
      interest was to understand the mechanisms governing cardiac impulse initiation.
      Research directions taken have fallen under the broad headings of gene therapy
      and cell therapy, and biomaterials research has also begun to enter the field. In
      this Review, we revisit certain milestones achieved through the construction of a
      'roadmap' in biological pacing. Whether the end result will be a clinically
      applicable biological pacemaker is still uncertain. However, promising constructs
      that achieve physiologically relevant heart rates and good autonomic
      responsiveness are now available, and proof of principle studies are giving way
      to translation to large-animal models in long-term studies. Provided that
      interest in the field continues, the next decade should see either biological
      pacemakers become a clinical reality or the improvement of electronic pacemakers
      to a point where the biological approach is no longer a viable alternative.

PMID- 21844919
TI  - The London position statement of the World Congress of Gastroenterology on
      Biological Therapy for IBD with the European Crohn's and Colitis Organisation:
      safety.
AB  - This paper in the series from the World Congress of Gastroenterology addresses
      the safety and immunogenicity of biological therapy. The safety profile in
      randomized controlled studies of all biological agents in Crohn's disease (CD)
      and ulcerative colitis has been generally favorable, but a small percentage of
      patients experience severe side effects on biological therapy, including
      pneumonia, tuberculosis, lymphoma, demyelination, drug-induced lupus, or
      hepatotoxicity. Although there is unequivocal evidence of an increased risk of
      serious infection among patients with rheumatoid arthritis treated with anti
      tumor necrosis factor therapy, the evidence is less clear in CD. The risk of
      infection may be increased by combination therapy with steroids and/or
      immunomodulators. There is a specific risk of the rare gamma delta hepatosplenic
      lymphoma that appears to have a predeliction for young males on combination
      therapy. The alpha4 integrin antagonist natalizumab also carries a specific risk
      of progressive multifocal leucoencephalopathy and reactivation of JC virus
      infection. The immunogenicity of biological therapy is complex: all agents are
      potentially immunogenic and this can be reduced by combination with
      immunomodulators. This may enhance both therapeutic efficacy and the risk of
      infection or malignancy, so the balance of risk and benefit must be judged for
      individual patients.

PMID- 21844920
TI  - Primary sclerosing cholangitis patients with serial polysomy fluorescence in situ
      hybridization results are at increased risk of cholangiocarcinoma.
AB  - OBJECTIVES: A polysomy fluorescence in situ hybridization (FISH) result in a
      pancreatobiliary brushing from a patient with primary sclerosing cholangitis
      (PSC) is very worrisome for carcinoma. However, treatment is not recommended
      unless verified by corroborative evidence of malignancy because of less than
      perfect test specificity in this population. The aim of this study was to
      evaluate the clinical outcome of PSC patients with serial polysomy FISH results.
      METHODS: Patients with PSC underwent endoscopic retrograde
      cholangiopancreatography with brushings when clinically indicated per standard
      practice. Brushings were evaluated by routine cytology and FISH. Retrospective
      review identified patients with a polysomy FISH result without definitive imaging
      or pathological evidence of malignancy at the time of the first polysomy, who
      underwent follow-up examinations including subsequent FISH testing (n=30).
      Patient records were reviewed to determine clinical outcome. RESULTS: In all, 9
      of 13 patients (69%) with a subsequent polysomy result (i.e., serial polysomy)
      were diagnosed with cholangiocarcinoma (CCA) compared with 3 of 17 patients (18%)
      with subsequent non-polysomy results (P=0.008). There was a significant
      difference in time to a diagnosis of CCA between PSC patients with serial
      polysomy compared with those with subsequent non-polysomy (P=0.01). In four
      patients with serial polysomy results, imaging/pathological evidence of CCA was
      not found until 1-2.7 years after the initial polysomy FISH result. CONCLUSIONS:
      FISH may detect polysomic cells in pancreatobiliary brushings before other
      pathological or imaging techniques identify CCA. Patients with serial polysomy
      FISH results are at higher risk for having CCA than those with subsequent non
      polysomy FISH results.

PMID- 21844921
TI  - Esophageal acid exposure decreases intraluminal baseline impedance levels.
AB  - OBJECTIVES: Intraluminal baseline impedance levels are determined by the
      conductivity of the esophageal wall and can be decreased in gastroesophageal
      reflux disease (GERD) patients. The aim of this study was to investigate the
      baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and
      in healthy controls. METHODS: Ambulatory 24-h pH-impedance monitoring was
      performed in (i) 24 GERD patients with and 24 without pathological esophageal
      acid exposure as well as in 10 healthy controls and in (ii) 20 patients with
      refractory GERD symptoms despite PPI, once on PPI and once off PPI. Baseline
      impedance levels in the most distal and the most proximal impedance channels were
      assessed. RESULTS: Median (interquartile range) distal baseline impedance in
      patients with physiological (2,090 (1,537-2,547) Omega) and pathological (781
      (612-1,137) Omega) acid exposure was lower than in controls (2,827 (2,127-3,270)
      Omega, P<0.05 and P<0.001). A negative correlation between 24-h acid exposure
      time and baseline impedance was observed (r=-0.7, P<0.001). In patients measured
      off and on PPI, median distal baseline impedance off PPI was significantly lower
      than on PPI (886 (716-1,354) vs. 1,372 (961-1,955) Omega, P<0.05) and distal
      baseline impedance in these groups was significantly lower than in healthy
      controls (P<0.05 and P<0.001). Proximal baseline impedance did not differ
      significantly between the patients off PPI and on PPI (1,793 (1,384-2,489) vs.
      1,893 (1,610-2,561) Omega); however, baseline impedance values in both
      measurements were significantly lower than in healthy controls (3,648 (2,815
      3,932) Omega, both P<0.001). CONCLUSIONS: These findings suggest that baseline
      impedance is related to esophageal acid exposure and could be a marker of reflux
      induced changes to the esophageal mucosa.

PMID- 21844922
TI  - Statins are associated with a reduced risk of gastric cancer: a population-based
      case-control study.
AB  - OBJECTIVES: Experimental studies have shown that statins have potential
      protective effects against cancer. The aim of this study was to investigate
      whether the use of statins was associated with gastric cancer risk. METHODS: We
      conducted a population-based case-control study in Taiwan. Data were
      retrospectively collected from the Taiwan National health Insurance Research
      Database. Cases consisted of all patients who were aged >=50 years and had a
      first-time diagnosis of gastric cancer for the period between 2005 and 2008. The
      controls were matched to cases by age, sex, and index date. Adjusted odds ratios
      (ORs) and 95% confidence intervals (CIs) were estimated by using multiple
      logistic regression. RESULTS: We examined 337 gastric cancer cases and 1,348
      controls. We found that ever-use of any statin was associated with a significant
      decrease in gastric cancer risk (OR=0.68, 95% CI=0.49-0.95). Compared with no use
      of statins, the adjusted ORs were 0.90 (95% CI=0.60-1.36) for the group having
      been prescribed statins with cumulative defined daily doses (DDDs) <134.25 and
      0.49 (95% CI=0.30-0.79) for the group with cumulative statin use of >=134.25
      DDDs. Also, there was a significant trend toward decreasing gastric cancer risk
      with increasing cumulative dose (chi(2) for linear trend=7.42, P=0.006).
      CONCLUSIONS: The results of this study are the first to suggest that statins may
      reduce the risk of gastric cancer.

PMID- 21844923
TI  - Withdrawing PPI therapy after healing esophagitis does not worsen symptoms or
      cause persistent hypergastrinemia: analysis of dexlansoprazole MR clinical trial
      data.
AB  - OBJECTIVES: Withdrawal of proton pump inhibitors (PPIs) may induce symptoms in
      healthy volunteers, suggesting that discontinuing PPI therapy induces acid-peptic
      disease. Similar assessments in patients with documented acid-related disorders
      are lacking. METHODS: We performed a retrospective analysis of data from 287
      Helicobacter pylori-negative erosive esophagitis (EE) patients healed after 4 or
      8 weeks of therapy with dexlansoprazole modified release (MR) or lansoprazole,
      and then randomized to placebo in 6-month maintenance trials. We compared serum
      gastrin levels and 24-h heartburn severity before enrollment in the healing
      trials (baseline) and after receiving placebo in the 6-month maintenance trials.
      RESULTS: Mean gastrin values at maintenance months 1 and 3 were essentially
      unchanged (median changes, 1.0 and -1.0 pg/ml), showing that gastrin normalized
      within 1 month of discontinuing PPIs and remained flat. Mean heartburn severity
      at maintenance month 1 was <1 on a 5-point scale (1=mild) and significantly lower
      than at baseline (median decrease, 0.41 points; P<=0.001). Heartburn severity in
      patients healed at week 4 or 8 with either PPI was generally similar, suggesting
      that neither longer exposure nor more potent therapy was associated with rebound.
      In those with month 2 data, mean heartburn severity at months 1 and 2 was
      significantly lower than baseline (median decrease, 0.54 and 0.58 points; both
      P<0.001), indicating an ongoing symptom response for 2 months after PPI
      withdrawal. CONCLUSIONS: In H. pylori-negative EE patients, there was no
      indication of recurring heartburn symptom worsening beyond baseline levels within
      2 months of discontinuing 4-8 weeks of PPI therapy.

PMID- 21844924
TI  - Teacher, supervisor, adviser, or mentor?

PMID- 21844928
TI  - Variability in patients with psoriasis: insights into the genotype-phenotype
      relationship.

PMID- 21844929
TI  - The dark side of regulatory T cells in psoriasis.
AB  - Psoriasis is a hereditary disease elicited by chronic activation of cutaneous T
      cells. Delineating the mechanistic interplay of the cell subsets involved is key
      to developing the next generation of effective treatments. In this issue,
      Bovenschen et al. report that regulatory T cells maintain a fine balance between
      the transcription factors Foxp3 and RORgammat. In patients with psoriasis, Tregs
      readily turn into IL-17-expressing cells, thus potentially perpetuating the
      inflammatory process that characterizes the disease. Results demonstrating that
      the histone/protein deacetylation inhibitor trichostatin A can block this
      conversion suggest that an epigenetic modification may underlie regulatory T-cell
      plasticity.

PMID- 21844930
TI  - The yin and the yang of keratin amino acid substitutions and epidermolysis
      bullosa simplex.
AB  - Mutations that change the same amino acid can result in different clinical
      phenotypes. Through in silico modeling and keratin filament assessment of
      genetically engineered HaCaT cells, Natsuga et al., as reported in this issue,
      have demonstrated how changes in charge and structure of a replacement amino acid
      in keratin 14 can cause disease (KRT14pA413P, EB simplex) or no clinical effect
      (KRT14pA413T, polymorphism).

PMID- 21844931
TI  - Interpretation of Skindex-29 scores.
AB  - In this Commentary, we compare two categorizations of a dermatological health
      related quality-of-life (HRQoL) instrument, the Skindex-29. One was created on
      the basis of an anchor-based method, the other on a distribution-based method.
      Differences between the two classifications are discussed, emphasizing the
      importance of the interpretability of HRQoL measures.

PMID- 21844932
TI  - [The price of greediness].

PMID- 21844933
TI  - [Childhood cancer and fertility].

PMID- 21844934
TI  - [Dislocated elbow fractures in the global world].

PMID- 21844935
TI  - [Wryneck in children should be investigated!].

PMID- 21844936
TI  - [We take the back pain patient seriously].

PMID- 21844937
TI  - Our data are good enough.

PMID- 21844938
TI  - [Low dosage naltrexone].

PMID- 21844939
TI  - [Should azithromycin dosing be changed?].

PMID- 21844940
TI  - Strategy plan for radiological research.

PMID- 21844941
TI  - Medicinal prevention of pre-diabetes--no purpose?

PMID- 21844942
TI  - [Trichorhinophalangeal syndrome--clinical presentation and genetics].
AB  - BACKGROUND: The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal
      dysplasia which has a characteristic clinical presentation and is classified in
      types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild
      and many patients probably remain undiagnosed. MATERIAL AND METHODS: The paper is
      based on four case reports and provides a short review of the condition. RESULTS:
      Our four patients all have typical facial features, such as a large nose and thin
      upper lip, thin hair and short curved fingers with characteristic radiological
      findings. The condition is autosomal dominant and caused by a mutation in the
      TRPS1 gene, which codes a gene-regulating protein involved in development of hair
      and modulation of chondrocytes. The diagnosis can be based on clinical findings,
      but DNA-analysis can be of help in unclear situations. Two of our patients were
      diagnosed from clinical and radiological findings, but for the two others genetic
      examinations were done as well. There is no causal treatment, but the diagnosis
      can give patients an explanation of their problems, and genetic counseling for
      the patient and family can be offered. Orthopedic surgery and cosmetic aids are
      valuable for many. INTERPRETATION: In an increasingly technified medical daily
      life, the clinical view is still the most important tool in diagnosing patients
      with this condition.

PMID- 21844943
TI  - [Living conditions and pattern of acute poisonings in Oslo].
AB  - BACKGROUND: Hospitalized patients with acute poisoning come from all classes of
      society. The relationship between living conditions and pattern of poisoning is,
      however, unclear. The aim of this study was to examine the connection between
      living conditions in Oslo and the pattern of acute poisonings, measured by
      incidence, main toxic agents and intention. METHODS: A one-year multi-centre
      study with prospective inclusion of all patients >= 18 years of age with a
      registered address in Oslo admitted to an Oslo hospital with acute poisoning from
      1 April 2003 through 31 March 2004. The 15 city districts were grouped into
      three, according to the official living conditions index in Oslo: city district
      group 1 (best living conditions), city district group 2 (average living
      conditions) and city district group 3 (most difficult living conditions).
      RESULTS: Of a total of 947 patients admitted with acute poisoning as their main
      diagnosis in the study period, 691 were included in the study, 660 of whom had
      self-inflicted poisoning. In city district group 3, the annual incidence of acute
      poisonings was 2.14 per 1000 inhabitants, significantly higher than city district
      group 2, with 1.50 (p < 0.001), and city district group 1, with 1.36 (p < 0.001).
      Measured as intention assessed by the treating physician, suicidal and drug
      related poisonings and those induced by a "cry for help" were more common in city
      district group 3 (0.74, 0.59 and 0.74 per 1000 inhabitants, respectively) than in
      city district group 2 (0.62, 0.40 and 0.41, respectively) and city district group
      1 (0.52, 0.32 and 0.45, respectively). The main toxic agents were predominantly
      benzodiazepines (20 %), ethanol (18 %) and paracetamol (12 %). There were no
      statistically significant differences in the distribution of main toxic agents
      between the city district groups. CONCLUSIONS: The findings show a social
      gradient, with the highest incidence of poisonings in the city district group
      with the most difficult living conditions.

PMID- 21844944
TI  - Fertility-preserving measures for girls and young women with cancer.
AB  - BACKGROUND: Children and young adults with cancer may be rendered infertile as a
      result of their treatment. The purpose of this article is to provide an overview
      of fertility-preserving measures for girls and young women. MATERIAL AND METHODS:
      The article is based on literature searches in the medical databases Medline,
      Pubmed and Scopus and the experience of a Nordic cooperative group on gonadal
      preservation in connection with cancer treatment. RESULTS: There are several
      methods for preserving the fertility of girls and young women with cancer. These
      should form a part of the actual cancer treatment. Cryopreservation of embryos is
      a well established method for adult cancer patients, also in Norway.
      Cryopreservation of eggs and ovarian tissue is to be regarded as still at the
      experimental stage. Research and new methods will improve the options for
      prepubertal children and young adults with disseminated cancer. INTERPRETATION:
      Multidisciplinary cooperation is necessary to ensure that children and young
      cancer patients receive thorough information about the risk of infertility after
      cancer treatment, and about potential fertility-preserving measures.

PMID- 21844945
TI  - Fertility-preserving measures for boys and young men with cancer.
AB  - BACKGROUND: Some types of cancer treatment entail a risk of reduced fertility and
      infertility. Fertility-preserving treatment can reduce the risk for some. The
      purpose of this article is to provide an overview of the risk of infertility
      after treatment of boys and young men with cancer and of fertility-preserving
      measures. MATERIAL AND METHODS: The article is based on literature searches in
      the medical databases Medline, Pubmed and Scopus and on the experience of a
      Nordic medical network collaboration. RESULTS: Cryopreservation of sperm is an
      established method for adult cancer patients in Norway. Vibratory stimulation of
      the penis and electroejaculation with subsequent freezing of sperm may be an
      option for young cancer patients who cannot manage to produce a semen sample with
      the aid of masturbation. Freezing of testicular biopsies may be an option for
      prepubertal boys who are not capable of producing mature sperm. INTERPRETATION:
      There are established methods for cryopreservation of sperm for adult cancer
      patients. The other fertility-preserving measures for boys and young men with
      cancer are regarded as experimental at present.

PMID- 21844946
TI  - [Blepharoptosis test with ice].

PMID- 21844947
TI  - [Scientific misconduct with colloid plasma substitutes].

PMID- 21844948
TI  - [Maternal health in Somalia--from doing something to making a difference?].

PMID- 21844951
TI  - [Expression and regulation of androgen receptor in the androgen-independent
      conversion of prostate cancer cells].
AB  - OBJECTIVE: To investigate the expression and regulation of androgen receptor (AR)
      in prostate cancer cells from androgen dependent to androgen independent.
      METHODS: LNCaP cells were cultured in charcoal-stripped serum for 6 months to
      establish androgen-independent celline (LNCaP-AI). Proliferation of LNCaP-AI was
      assayed by cell viability. Expression of AR mRNA and protein was analyzed by RT
      PCR and Western blot. Wnt signaling pathway inhibitor IWR-1 and proteasome
      inhibitor lactacystin were used to investigate effects of Wnt and proteasome
      pathway on AR expression in LNCaP-AI. RESULTS: LNCaP-AI exhibit enhanced
      proliferation and up-regulated PSA expression compared with LNCaP. During
      androgen deprivation, AR mRNA was up-regulated in a short early stage and then
      declined to a stable level in LNCaP-AI compared with LNCaP, but AR protein kept
      in downward trend. The mRNA and protein expression of AR was decreased by IWR-1
      treatment. AR protein but not mRNA was increased by lactacystin treatment.
      CONCLUSION: The androgen independent prostate cancer cell line was established by
      androgen deprivation, in which the protein expression of AR was dramatically
      decreased. mRNA and protein expression of AR in LNCaP-AI was related to Wnt
      signaling pathway and proteasome pathway. Increased Wnt signaling or decreased
      proteasome pathways contribute the decreased AR protein expression.

PMID- 21844952
TI  - [Expression of glycoprotein non-metastatic melanoma protein B in prostate cancer
      and its significance].
AB  - OBJECTIVE: To investigate the expression of glycoprotein non-metastatic melanoma
      protein B (GPNMB) in prostate cancer and its clinical significance. METHODS: The
      expression of GPNMB was analysed in 63 prostate cancer and 3 heterosexual
      hyperplasia prostate tissue and 8 benign prostatic hyperplasia samples by
      immunohistochemical staining, with integral optical density(IOD) value
      representing expression level of positive cells. RESULTS: The expression of GPNMB
      was lower in benign prostatic hyperplasia (BPH, IOD=70 017.49) than in Atypical
      hyperplasia (IOD=101 547.33, P=0.000 1) . The expression of GPNMB in tumor (IOD=
      162 027.54) was higher than in non-tumor group (IOD=79 290.97), which included
      BPH and atypical hyperplasia (P=0.000 1). But GPNMB expression level was not
      positively elevated with degree of malignancy of prostate cancer. However, the
      expression of GPNMB in low pathological grading(IOD=177 944.30) was higher than
      that in high pathological grading(IOD=150 885.81, P=0.013). CONCLUSION: The
      abnormal expression of GPNMB may play an important role in the development of
      prostate cancer and its detection may be useful for the early diagnosis of
      prostate cancer.

PMID- 21844953
TI  - [Effects of icariin and icariside II on eNOS expression and NOS activity in
      porcine aorta endothelial cells].
AB  - OBJECTIVE: To investigate the effects of icariin and icariside II on eNOS
      expression and NOS activity in endothelial cells and possible mechanisms using
      EGFR over-expressed porcine aorta endothelial (PAE) cell line. METHODS: The EGFR
      gene was transfected into PAE cells and genetic stable cell line (PAE-EGFR) was
      selected. 12.5 MUmol/L of icariin and of icariside II were used to treat the PAE
      and PAE-EGFR cells respectively for 48 h, the eNOS expression in each group was
      observed. EGF was also used to treat the cells to observe the regulatory effects
      of icariin and icariside II on NOS activity. The regulatory effects of icariin
      and icariside II on NOS activity were also observed, and sildenafil was used as a
      control. RESULTS: Western blot showed that the basic value of eNOS expression was
      higher in PAE-EGFR group compared with that in PAE group, both of icariin and
      icariside II increased the eNOS expression in PAE and PAE-EGFR group (P<0.01),
      and the value of eNOS expression was higher in PAE-EGFR group than that in PAE
      group. In the PAE-EGFR cell line, the NOS activity reached (15.37 +/- 1.49) u/mg
      when the concentration of icariside II was 10(-8) mol/L, which was 4.66 u/mg more
      than that in the PAE cell line. When the concentration reached 10(-7), 10(-6) or
      10(-5) mol/L, the change of NOS activity in PAE-EGFR group was greater than that
      in PAE group (P<0.01). icariin also increased the NOS activity in PAE and PAE
      EGFR cells, but the activity was 20% lower compared with icariside II group,
      however, Sildenafil showed no influence on NOS activity. CONCLUSION: Icariin and
      icariside II may increase the eNOS expression through activating EGF-EGFR pathway
      in PAE cell, by which endothelial cells function could be regulated and the
      better effect was noted in icariside II compared to icariin.

PMID- 21844954
TI  - [Changes in morphology and steroidogenic function of aged human Leydig cells].
AB  - OBJECTIVE: To investigate the changes of morphology and steroidogenic function in
      aged human Leydig cells and to understand the mechanism of late onset
      hypogonadism (LOH). METHODS: Ten young and ten aged male subjects were enrolled
      in this study. AMS (Aging Male's Symptoms) scale was used for symptom evaluation.
      Testes species with LOH were utilized as the research model. Then the
      histological changes in testis and ultrastructure of Leydig cells were observed
      by HE staining and electron microscopy (EM), respectively. The serum total
      testosterone concentrations were measured by an ELISA kit. The expressions of
      steroidogenic acute regulatory (StAR) protein and cholesterol-side-chain cleavage
      enzyme (P450scc) were detected by western blot. RESULTS: The scores of AMS in the
      aged group were higher than those in the young group with decreased serum
      testosterone levels (61.25 +/- 7.08 vs. 20.75 +/- 3.73,P<0.001). And the serum
      testosterone level of the aged human was lower than that of the young human
      [(3.12 +/- 0.58) MUg/L vs. (6.29 +/- 1.17) MUg/L,P<0.05]. HE staining showed that
      degenerative changes occurred in the aged human testes. And many swollen
      mitochondria with mitochondrial cristae that disappeared were found in Leydig
      cells of the aged human by EM. The serum total testosterone level of the aged
      human was significantly lower than that of the young group. And the expressions
      of StAR and P450scc protein in the aged group were significantly lower than those
      of the young group. CONCLUSION: Mitochondrial swelling and decreased expressions
      of StAR and P450scc were closely related to the reduced ability of testosterone
      synthesis in aged males. And the exact mechanism needs further investigation.

PMID- 21844955
TI  - [Abnormal expression and significance of MIR-184 in human renal carcinoma].
AB  - OBJECTIVE: To explore the role of microRNA-184(MIR-184) in the development of
      renal cell carcinoma(RCC). METHODS: The expressions of MIR-184 in 51 patients
      with RCC Investigated, normal adjacent tissues (ADTs) matched by fluorescence
      quantitative PCR technology (RT-qPCR) and the correlations analyzed between MIR
      184 expression and the age, gender and clinical stage of RCC patients. RESULTS:
      The average expression of MIR-184 in RCC was -14.664 6 +/- 5.362 4, while that in
      ADTs was -10.408 7 +/- 3.482 7(P<0.01). Bounded with the MIR-184 expression in
      RCC, patients were divided into lower-expression group and higher-expression
      group. Meanwhile, the RCC patients were divided into three groups according to
      the age, gender and clinical stage of the patients. Chi-square statistical
      analysis showed that the expression level of MIR-184 was not significantly
      correlated with the patient's age, gender and clinical stage (respectively:
      P>0.03, P>0.99, P>0.03). CONCLUSION: MIR-184 in RCC was significantly lower than
      that in ADTs, which may have potential significance in the occurrence and
      development of RCC.

PMID- 21844956
TI  - [Study on the correlation of the 5-HTTLPR polymorphism with premature ejaculation
      in Han Chinese population].
AB  - OBJECTIVE: To investigate the relationship between 5-HT transporter gene-linked
      polymorphism (5-HTTPLR) and the clinical characters of premature ejaculation in
      Han Chinese population. METHODS: By case-control study approach, we set primary
      premature ejaculation (PPE) group (119 cases), secondary premature ejaculation
      (SPE) group (60 cases) with IELT < 1 min in more than 90% coitus and normal
      control group (90 cases) with IELT >= 3 min. The gene polymorphism of the 5-HTT
      was detected by polymerase chain reaction analysis in all the cases, and the gene
      frequency differences among the three groups were evaluated. RESULTS: The
      frequency of the genotype S/S was higher in PPE group than in normal control
      group(51.3% vs. 37.8%,P<0.01), and the frequency of genetype L/S was lower in PPE
      group than in normal vontrol group(28.6% vs. 34.4%,P<0.05).The S allele was
      higher in PPE group than in control group (P<0.05), but there was no difference
      between the SPE group and the normal control group. CONCLUSION: The 5-HTTLPR
      polymorphism is associated with PPE, which shows that genetics may play an
      important role in the occurrence of PPE but not of SPE. The etiology of PPE and
      SPE is different.

PMID- 21844957
TI  - [Prostatic adenocarcinoma with glomeruloid structure].
AB  - OBJECTIVE: To investigate the architectural features and frequency of glomeruloid
      features in pathological section of prostatic adenocarcinoma and evaluate the
      association between glomerulations and its clinical data. METHODS: We studied 196
      prostatic adenocarcinoma specimens obtained from needle biopsies or radical
      prostatectomy and their clinical data, and reviewed related literatures. RESULTS:
      Three of the 196 cases showed glomeruloid features, the Gleason score of which
      was 7, 8, and 8, respectively. Of the 3 cases 1 had osseous metastasis and 2
      extraprostatic nervus extension. After 5 to 15 months' follow-up, 1 case died and
      the other 2 still under treatment. CONCLUSION: Glomeruloid structures in the
      prostate represented an uncommon but distinctive growth pattern that was specific
      for malignancy. Glomeruloid structures were usually seen in high-grade
      adenocarcinoma, often with extraprostatic extension.

PMID- 21844958
TI  - [Gender-related differences in pathological characteristics of upper urinary
      tract urothelial carcinoma: analysis of 597 cases].
AB  - OBJECTIVE: To assess the sex differences in pathologic characteristics of Chinese
      patients with upper urinary tract urothelial carcinoma (UUTUC). METHODS: Between
      January 2004 and December 2010, 597 patients (253 men and 344 women) underwent
      surgical management at Peking University First Hospital for pathologically proven
      UUTUC. We reviewed pathological data from these patients, and used univariate
      analysis to determine sex differences. RESULTS: Of the 597 consecutive cases,
      mean age was 67 years ranging from 20 to 94 years. Univariate analyses showed
      that female patients had less proportion of large tumor (P=0.017), local advanced
      tumor (P<0.001) and lymph node metastasis (P=0.022). No significant sex-related
      differences were found in the age, tumor grade, and tumor number. CONCLUSION: In
      Chinese UUTUC patients, female patients were more common. Females are less likely
      to have more advanced pathologic stage than males.

PMID- 21844959
TI  - [Protective effect of heat shock protein 70 and magnesium sulfate supplementation
      on renal ischemia reperfusion injury].
AB  - OBJECTIVE: To investigate whether there is a protective mechanism in exogenous
      magnesium ions supplement in renal ischemia reperfusion injury(IRI ), and to
      study the expression of heat shock protein 70 (HSP70) and HSP70-mRNA in the
      reperfusion injury. METHODS: A total of 90 male Japanese white rabbits (1.8-2.0
      kg) were divided into three groups: ischemia reperfusion group (I-R), MgSO4
      pretreatment group and sham operation group. The right kidney was cut through
      median abdominal incision to make solitary kidney model. The left renal artery
      was blocked for 1 h in I-R group and MgSO4 group. 2.5% MgSO4 1 mL/(kg*h) was
      given through ear vein before the artery was blocked and during the blockeage in
      the MgSO4 group. the kidney cortex tissue was taken 1, 2, 4, 24, 48 and 72 h
      after reperfusion. Immunohistochemical examination was used to determine the
      HSP70 expression. A modified quantitative Real time-PCR was used to quantitate
      HSP70-mRNA in the three groups. Pathological examination was also used to confirm
      the results. RESULTS: Real time-PCR showed that HSP70-mRNA began to increase at
      the end of 1 h, and reached the peak at the end of 2 h in both I-R and MgSO4
      groups, but expression in I-R group which was remarkably higher than that in the
      MgSO4 group at the end of 2 h and 4 h ( P<0.05). HSP70-mRNA levels decreased
      rapidly at the end of 24 h. In I-R group, moderate HSP70 expression could be seen
      in the proximal tubules during immunohistochemical examination after reperfusion
      for 24 h and 48 h. By contrast, there was weak HSP70 expression in the MgSO4
      group 24 h and negative 48 h after reperfusion. Epithelial shedding, border
      brush, inflammatory cell infiltration and protein casts were serious after 24 to
      48 h reperfusion, while only slight tubular cell shedding and necrosis could be
      found in the MgSO4 group at the matched time. CONCLUSION: Magnesium supplement
      can significantly relieve the renal ischemia reperfusion injury. It can inhibit
      the upregulated expression of HSP70 and HSP70-mRNA in vivo, which demonstrates
      that the expression of HSP70 is not necessary in the protective mechanism.

PMID- 21844960
TI  - [Complete transperitoneal laparoscopic nephroureterectomy for upper urinary tract
      urothelial carcinoma].
AB  - OBJECTIVE: To discuss the surgical skills and clinical value of complete
      transperitoneal laparoscopic nephroureterectomy. METHODS: We collected and
      analyzed the clinical data of 25 patients (14 renal pelvic carcinoma and 11
      carcinoma of ulreter, right side 15 and left side 10) who underwent complete
      transperitoneal laparoscopic nephroureterectomy for the upper urinary tract
      urothelial carcinoma (UUT-UC) in Peking University First Hospital from May 2010
      to April 2011. RESULTS: All the operations were successfully done by one surgeon
      with standard 4 or 5 trocars technique. The mean operative time was 150 min (120
      180 min), the blood loss about 20-100 mL (mean 40 mL) and no severe complications
      observed. The postoperative hospital stay was 4-6 days with an average length of
      5.5 days. The mean follow-up was 5.5 (1-11) months. One of 19 patients underwent
      trans urethral resection of bladder tumour (TURBT) for recurrent non-muscle
      invasive bladder tumor. CONCLUSION: Complete transperitoneal laparoscopic
      nephroureterectomy is a minimally invasive, safe and effective way to treat UUT
      UC. The patients recover soon and have a shorter length of stay.

PMID- 21844961
TI  - [Efficacy and safety of transumbilical single-port laparoscopic radical
      nephrectomy].
AB  - OBJECTIVE: To evaluate the efficacy and safety of transumbilical single-port
      laparoscopic radical nephrectomy. METHODS: The clinical data of laparoscopic
      radical nephrectomy performed from June 2010 to October 2010 in Peking University
      Third Hospital were analyzed retrospectively. In the study, 10 patients underwent
      transumbilical single-port laparoscopic radical nephrectomy (LESS) and 15
      received retroperitoneal laparoscopic radical nephrectomy. The data on general
      presentation, tumor size, tumor location, operative time, blood loss,
      complications, Visual Analog Pain Scale (VAPS), postoperative hospital stay,
      pathological results were collected to compare between the two groups. Our
      homemade single-site equipment was used in the LESS approach and the kidney was
      dissociated after being cut off the renal vessel and extracted through the
      umbilical incision. The retroperitoneal approach followed the standard surgical
      procedures, and the specimens were removed from the extended incision. RESULTS:
      All the procedures were completed without conversion to open radical nephrectomy.
      Compared with traditional laparoscopic surgery, the operative time (P=0.001) and
      VAPS (P=0.002) showed significant difference in LESS group,and no difference was
      noted in other factors (P>0.05). There was no secondary bleeding, wound
      infection, intestinal obstruction, incision hernia and other severe postoperative
      complications. The follow-up of 6 to 10 months showed no local recurrence.
      CONCLUSION: Transumbilical single-port laparoscopic radical nephrectomy is
      feasible, effective and safe. It gives a more mini-invasive and cosmetic option
      for young or female patients.

PMID- 21844962
TI  - [Feasibility analysis of laparoscopic transperitoneal and transmesenteric
      pyeloplasty in recurrent ureteropelvic junction obstruction].
AB  - OBJECTIVE: To discuss the feasibility and safety of laparoscopic transperitoneal
      and transmesenteric pyeloplasty for recurrent ureteropelvic junction obstruction
      (UPJO). METHODS: From May 2006 to June 2008, we admitted 5 cases of recurrent
      UPJO who had received open retroperitoneal pyeloplasty with 3 males and 2
      females. They were 19 to 32 years old with the average of 24.5 years and suffered
      from recurrent UPJO 3 to 16 years with the average of 7.8 years after operation.
      They felt discomfort in the lumbar region to different extent and their
      intravenous pyelography (IVP) or computerized tomography for urinary system (CTU)
      showed typical UPJO. The nucleotide renal scan (NRS) revealed that the renal
      excretion was slow, even after intravenous injection of diuretics. The
      laparoscopic transperitoneal and transmesenteric pathway was done in such a way
      that the incision was longitudinal at the mesentery of small intestine near the
      affected ureteropelvic junction (UPJ). The UPJ was isolated to avoid injuring the
      intestine and the mesenteric blood vessels. The UPJO was removed with the routine
      Anderson-Hynes technique and the anastomosis between pelvis and ureter was
      carried out by 2 separate and running sutures. RESULTS: The operating time was
      105-230 min with the average of 165 min and the estimated blood loss was 50 to
      120 mL with the average of 75 mL. Patients left bed on the first day and the
      drainage tube was taken out on the 4th to 5th day after the operation. There were
      no other injuries and complications. By October of 2008, they had been followed
      up for 33 to 49 months with the average of 37.5 months and IVP or CTU and the
      diuretic NRS showed smooth excretion of the operated UPJ. CONCLUSION: As for
      experienced hands, the laparoscopic transperitoneal and transmesenteric
      pyeloplasty is feasible and safe for recurrent UPJO, but it's not recommended to
      the beginners of laparoscopic procedures.

PMID- 21844963
TI  - [Analysis of perioperative complications of laparoscopic radical cystectomy for
      bladder cancer].
AB  - OBJECTIVE: To evaluate operation process and perioperative complications of
      patients who underwent laparoscopic radical cystectomy (LRC). METHODS: The
      clinical data of 49 cases of LRC from October 2004 to June 2010 were reviewed
      retrospectively. Perioperative complications and mortality were analyzed, and so
      were the operative time, blood loss and postoperative hospital stay.
      Perioperative complications were defined as any adverse event within 30 days of
      surgery. All complications were graded according to an established five-grade
      modification of the original Clavien system. RESULTS: The mean operation time was
      418 minutes, the mean blood loss was 514 mL, the transfusion rate was 36.7%, the
      mean transfusion volume was 578 mL, and the average postoperative hospital stay
      was 20 d. For urinary diversion, ileal conduits were constructed in 27 patients
      (55.1%), ileal neobladders in 16 patients (32.7%), and ureterocutaneostomies in 6
      patients (12.2%). A total of 17 patients (34.7%) developed at least one
      perioperative complication. Complications of grades 1-2 occurred in 12 patients
      (24.5%), which included subileus, urinary tract infections, deep venous
      thrombosis of the lower limbs, pneumonia, etc. Complications of grades 3-5
      occurred in 5 patients(10.2%), and one patient died of pulmonary embolism. Ileal
      neobladders and ileal conduits were similar at the operation time, blood loss,
      transfusion rates, postoperative hospital stay and morbidity of perioperative
      complications. CONCLUSION: Morbidity of perioperative complications following LRC
      was still high. The most frequent complications were subileus and urinary tract
      infections. The surgery should be performed on selected patients, and measures
      need to be taken to prevent these complications. Compared with ileal conduits,
      ileal neobladders did not increase the operation time, blood loss and morbidity.

PMID- 21844964
TI  - [Clinical safety and efficacy of a novel intracorporeal combined pneumatic and
      ultrasonic lithotriptor (CQS-01) compared with Swiss LithoClast Master (EMS
      III)].
AB  - OBJECTIVE: To evaluate the safety and efficacy of a new intracorporeal pneumatic
      and ultrasonic lithotriptor (CQS-01). METHODS: Eighty-six patients with renal or
      upper ureteral stones suitable for percutaneous nephrolithotomy (PNL) treatment
      were randomly divided into trial group (treated with CQS-01 device) and control
      group (treated with EMS-III device), with 43 patients in either group
      respectively. All the patients were followed up for 7 +/- 3 days post-operation.
      The data were collected and analyzed with regard to stone burden, postoperative
      stone clearance rate, operation time, stone fragmentation and extraction time,
      volume of extracted stones, changes of red blood cells (RBC) and hemoglobin (Hb),
      occurrence rate of transfusion, changes of blood urea nitrogen (BUN) and
      creatinine (Cr), serum electrolytes, white blood cells (WBC), as well as body
      temperature and adverse events rate at 24 hours and 7 +/- 3 days post PNL
      operation. RESULTS: No significant differences were found between the trial group
      and the control group (P>0.05), in terms of patients demography, renal
      characteristics and stone characteristics. In the trial group and the control
      group, respectively: the postoperative stone-free rate was 76.74% and 79.07%
      (P=0.796) and the partial stone clearance rate was 23.26% and 20.93% (P=0.796),
      the operation time was (92.49 +/- 76.59) min and (87.28 +/- 50.01) min (P=0.485),
      the stone fragmentation and extraction time was (50.16 +/- 57.11) min and (40.59
      +/- 31.01) min (P=0.976), the volume of extracted stones was (10.85 +/- 20.08) mL
      and (5.05 +/- 6.00) mL (P=0.041). There were also no significant differences in
      postoperative RBC and Hb drops, occurrence rate of transfusion, post-operative
      BUN and Cr, body temperature changes, postoperative systemic inflammatory
      response and adverse events rate at 24 hours and 7 +/- 3 days post-operation
      between the trial and control groups (P>0.05). CONCLUSION: There is no
      significant difference in clinical safety, efficacy, and the stone clearance
      capability between CQS-01 device and EMS-III device.

PMID- 21844965
TI  - [Clinical efficacy and safety of percutaneous nephrolithotomy for upper urinary
      tract calculi patients with metabolic syndrome].
AB  - OBJECTIVE: To investigate the efficacy and safety of percutaneous nephrolithotomy
      (PCNL) for upper urinary tract calculi patients complicated with metabolic
      syndrome (MS). METHODS: The clinical data of 66 PCNL cases with upper urinary
      tract calculi from March 2010 to February 2011 were retrospectively reviewed.
      Patients were divided into two groups according to 2004 Diagnostic Criteria of
      Metabolic Syndrome by the Chinese Diabetes Society (CDS). Twenty six upper
      urinary tract calculi patients complicated with metabolic syndrome were defined
      as case group (average aged 52.4 years, 16 males and 10 females). The other 40
      cases without MS served as control group (average aged 45.9 years, 21 males and
      19 females). The stone burden was (7.2 +/- 1.8) cm(3) in case group and (6.4 +/-
      1.3) cm(3) in control group (P=0.712). The stone free rate, operative time, drop
      in hemoglobin level and fever were compared between the two groups. RESULTS: The
      operation time was (87.1 +/- 9.0) min in case group and (87.6 +/- 6.0) min in
      control group (P=0.963). The stone free rate was 76.9% (20/26) vs. 75.0% (30/40),
      P=0.859. The drop in hemoglobin level was (8.4 +/- 1.6) g/L vs. (9.1 +/- 1.4)
      g/L, P=0.739. The incidence of post-operative fever was 38.5% (10/26) vs. 45.0%
      (18/40), P=0.599. CONCLUSION: MS will neither increase the difficulty of surgery,
      nor reduce the stone free rate of PCNL for upper urinary tract calculi. And it
      will not raise the incidence of postoperative complications.

PMID- 21844966
TI  - [Efficacy of transurethral resection of ejaculatory duct for treatment of
      ejaculatory duct obstruction: report of 60 cases].
AB  - OBJECTIVE: To evaluate the effect of transurethral resection of ejaculatory duct
      (TURED) for treatment of ejaculatory duct obstruction (EDO). METHODS: The
      clinical data of 60 cases of EDO from Oct. 2004 to Oct. 2010 were analyzed. The
      diagnostic criteria included semen analyses, fructose in seminal plasma,
      transrectal ultrasonography (TRUS), and vasography if necessary. All the patients
      were treated by TURED. Post-operative semen assay, postoperative patency rate and
      postoperative impregnation rate were followed. RESULTS: Semen analyses in the
      majority of cases showed the typical characteristics of EDO, azoospermia, low
      semen volume (average 1.10 +/- 0.76 mL), low pH (average 6.5 +/- 1.4), absent or
      low semen fructose (average 5.86 +/- 2.19 MUmol/one ejaculation). TRUS showed
      pure dilation of both ejaculatory ducts in 15 cases, prostatic cyst in 6, pure
      dilated seminal vesicles on both sides in 10, unilateral dilated seminal vesicle
      in 4, dilation of both ejaculatory duct and seminal vesicles in 10, dilated
      seminal vesicles with prostatic cyst in 5, unilateral dilated seminal vesicle and
      contralateral aplasia of seminal vesicle in 2, dilated seminal vesicles with
      dilation and calcifications of both ejaculatory ducts in 3. The remaining 5 had
      unilateral dilated ejaculatory duct and seminal vesicle with contralateral
      aplasia of seminal vesicle. In all the cases followed up more than 6 to 78 months
      after TURED, 51 patients (85.0%) had improved semen parameters and 16 patients'
      wives (26.7%) had pregnancies. CONCLUSION: TURED may be the simple, minimally
      invasive and effective method for the treatment of EDO.

PMID- 21844967
TI  - [Factors affecting the results of microsurgical vasoepididymostomy].
AB  - OBJECTIVE: To evaluate the intraoperative factors affecting the patency of
      microsurgical vasoepididymostomy. METHODS: From January 2009 to July 2010, 73 men
      with obstructive azoospermia had undergone longitudinal intussusception
      vasoepididymostomy (LIVE). The mean age (range) was 31 years (23 to 48) for the
      patients and their mean infertility was 50.9 months (2 to 180). All the patients
      were included in three groups by the clinical variables in surgery: anastomosis
      number, anastomosis sites, epididymal fluid analysis. Bilateral and lateral
      anastomosis was in 50 and 23 cases, respectively. The anastomosis on caput,
      corpus and caudal was in 19, 46, and 8 cases respectively. Motile sperm in the
      epididymal fuild continuing flowage could be found in 55 patients. By contrast,
      immotile sperm could be found in 18 patients. Semen analysis was done at the end
      of 3 months, and patency was arbitrarily defined as >10 000 sperm/mL in ejaculate
      in at least one semen analysis after surgery. RESULTS: Of all the patients, 53
      were followed up. Sperm was present in the ejaculate in 38 patients
      postoperatively. The overall patency rate was 71.7% (38/53). Patency rates of
      bilateral surgery and of lateral surgery achieved 80.7% and 27.6%; of caput
      anastomosis 38.5%, of corpus anastomosis 78.8%, of caudal anastomosis 100%, of
      motile sperm with epididymal fluid continuing flowage 83.7% and of immotile sperm
      40%, respectively. In the study, 17 patients (33.3%, 17/53) reported spontaneous
      pregnancy. CONCLUSION: Except for microsurgical technology, bilateral
      anastomosis, corpus or caudal anastomosis, and motile sperm with epididymal fluid
      continuing flowage may improve patency rate postoperatively.

PMID- 21844968
TI  - [Risk factor analysis of post-operative complications in radical cystectomy for
      bladder transitional cell cancer: retrospective assessment from 208 consecutive
      cases].
AB  - OBJECTIVE: To describe early complications (within 90 days) after radical
      cystectomy and to analyze the associated specific risk factors. METHODS: The
      clinical data from 208 consecutive cases of muscle invasive bladder cancer were
      collected and reviewed. Potential variables predictive of early morbidity were
      retrospectively analyzed. RESULTS: Of the 208 subjects, 160 (76.9%)developed at
      least 1 postoperative complication and 46 (22.2%) at least 2 complications. The
      most frequent complications presented were blood loss (75 cases), post-operative
      renal insufficiency (31 cases), and intestinal obstruction (29 cases). In
      univariate analysis, operative time, hypertension and preoperative creatinine
      level were associated with the development of complications. On multivariate
      analysis, operative time, preoperative creatinine level were the significant
      factors. CONCLUSION: Morbidity remains high after radical cystectomy. The
      operative time, preoperative creatinine level and hypertension may be associated
      with the postoperative complications. Acknowledgement of the patients' specific
      risk factors and monitoring perioperative processes may incrementally reduce
      risks and improve outcomes of the patients.

PMID- 21844969
TI  - [Application of ureteral realignment under the guidance of ureteroscope in
      iatrogenic ureteral injuries].
AB  - OBJECTIVE: To determine the value of ureteral realignment under ureteroscope in
      the treatment of iatrogenic ureteral injury. METHODS: In the study, 14 cases of
      ureteral injury were caused by gynecological laparoscopic surgery, with mean age
      being 46 (24 to 71) years. Including 1 bilateral injury, 10 right ureteral
      lesions and 3 left ureteral lesions, 9 of the 15 ureteral lesiors had both
      ureteral fistula and obstruction, and 6 had complete ureteral obstruction. The
      diagnosis was delayed with a median time of 20 (0 to 207) days. Uronephrosis
      ranged from 2.5 to 4.2 cm, and creatinine level of drainage or vaginal discharge
      was 2 439 (655 to 6 317) MUmol/L. Complete ureteral obstruction and urinary
      fistula were seen under a combined retrograde and antegrade study. A guidewire
      could not pass across the injured area of the ureter. Guidewire was indwelled in
      the proximal end ureter by nephrostomy, ureter incision was preformed with the
      ureteroscope under the guidance of fluoroscopy, realignment of proximal and
      distal end of ureteral lesion was made at once, and stents were indwelled.
      Altogether, 15 operations were performed. B-us, KUB, IVP and long term follow up
      were carried out after the operation. RESULTS: Ureteral realignments were
      successful in 14 patients, all stents were in position, and retention time of the
      stents was 12 months. Follow up time lasted from 185 to 964 days. No recurrence
      hydronephrosis was ever seen after the operation. CONCLUSION: Awareness of ureter
      protection should be enhanced within laparoscopic surgery; Ureteral realignment
      under ureteroscope can remedy iatrogenic ureteral injuries by simple and minimum
      invasive operation, and it can also avoid the open operation.

PMID- 21844970
TI  - [Clinical significance of radical cystectomy with extended lymphadenectomy].
AB  - OBJECTIVE: To evaluate the prognosis of patients treated with radical cystectomy
      and extended lymphadenectomy for invasive bladder cancer and to describe the
      association of the primary bladder tumor grade, stage, lymph node status and
      lymph node density with clinical outcomes. METHODS: A retrospective analysis was
      done of 32 consecutive cases with bladder cancer who received radical cystectomy
      and extended lymph node dissection from January 2006 to December 2010 in the
      Department of Urology, Peking University First Hospital. All the patients were
      scheduled for the follow-up. The survival data were analyzed with the tumor
      grade, stage, lymph node status and other factors that might relate to the
      prognosis by statistics. RESULTS: All the cases were diagnosed as invasive
      urothelial bladder cancer by preoperative biopsy or TUR-Bt. During the follow-up,
      6 patients (18.8%) got disease progression, and 4 patients died (12.5%). Overall
      survival rate was 87.5%. In 32 patients, 17 months and 3 year survival rates were
      (88.7 +/- 12.1)% and (81.8 +/- 17.0)%, respectively. From the tumor grade point
      of view, 6 patients belonged to G2, and 26 cases G3. All deaths were graded G3.
      G3-class 3-year survival rate was (74.6 +/- 23.9)% (P> 0.05, compared with G2).
      From the analysis of stage, T1 and T2 stages had no death during the follow-up.
      The 17-month survival rate of T3 group was (60.0 +/- 42.9)%, the 8-month survival
      rate of T4 group was (87.5 +/- 22.9)%. There were 9 patients with positive lymph
      nodes (28.1%) and 23 with negative in (71.9%). The number of dissection lymph
      nodes was from 7-50 ( average 22.8 ). The 17-month survival rate of patients with
      positive lymph node was (50.0 +/- 44.6)%. The 3-year survival rate of patients
      with negative lymph node was (92.3 +/- 14.5)% (P<0.05). The 3-year survival rate
      of patients with lymph node density less than 20% was (88.8 +/- 15.4)%. The 8
      month survival rate of patients with lymph node density greater than 20% was
      (66.7 +/- 53.3)% (P<0.05). CONCLUSION: Radical cystectomy with extended lymph
      node dissection can improve the prognosis of patients with invasive bladder
      cancer. Tumor stage, lymph node status and lymph node density are closely related
      to the patient's survival.

PMID- 21844971
TI  - [Clinical analysis of urothelial cancer after renal transplantation].
AB  - OBJECTIVE: To analyze and summarize the risk factors of malignant tumor after
      renal transplantation. METHODS: We retrospectively analyzed 435 renal recipients
      who underwent renal transplantation in our institute from May 1991 to March 2011,
      and found 14 patients developed malignant tumor, of which 12 were from our
      institute, and the other 2 were referred from other institute. We analyzed the
      risk factors of those tumors for their incidence, classification, time of final
      diagnosis, immunity suppression therapy and prognosis. RESULTS: The incidence of
      malignant tumors after renal transplantation in our hospital was 2.8%.Of the 14
      cases, 11 were urothelial tumor (6 cases developed both in pelvis and ureter, 2
      cases of primary ureter cancer and 3 cases of primary bladder cancer), and the
      other 3 were thyroid carcinoma, colon carcinoma and lymphoma. We carried out
      radical corrections in 13 patients,of whom 10 were in good status, 2 underwent
      the secondary operation in 1 year due to relapse (one patient died in half a year
      due to tumor size expansion), and 1 died from repeated relapse in 3 years.
      Chemotherapy was used for the patient with lymphoma. CONCLUSION: Immunity
      suppression and surgery are associated with the high incidence of maglinant tumor
      (78% were urinary tract tumors) after renal transplantation. The risk of tumor is
      strongly associated with the recipient's survival. The key point of management is
      early diagnosis and treatment. Further attention should be emphasized to painless
      gross hematuria, unconfirmed back pain, hydronephrosis, hydroureter and
      infections.

PMID- 21844972
TI  - [Clinical characteristics of patients with erectile dysfunction-no sexual life].
AB  - OBJECTIVE: To collect clinical data of patients with erectile dysfunction-no
      sexual life (ED-NS), and investigate its characteristics with a simple evaluating
      questionnaire. METHODS: Sixty-one patients who complained erectile dysfunction
      without sexual life for more than six months and 57 normal controls were enrolled
      in our study. The mean age of the ED-NS patients was 26.2 +/- 4.3 years, compared
      with 24.9 +/- 4.1 years of normal controls, without significant difference
      (P>0.05). The erectile function was assessed with a simple questionnaire
      including 16 questions, such as sexual libido, general erectile function,
      nocturnal penile erection, erectile function during foreplay without sexual life,
      erectile function during audio-video sexual stimulation, confidence, depressions,
      etc. The patients filled "yes" or "no" in the blank of the questionnaire
      according to their erectile function. The frequency distributions of each
      question between the two groups were analyzed with chi-square test of four-fold
      table. RESULTS: Compared with normal control group, the frequency distributions
      of 13 questions in ED-NS group were significantly different, such as sexual
      libido (chi2=35.891, P<0.05), confidence of erection (chi2=75.608, P<0.05),
      general erectile function(chi2=54.433, P<0.05), nocturnal penile
      erection(chi2=29.815, P<0.05), erectile function during foreplay without sexual
      life(chi2=21.211, P<0.05), confidence of erection during foreplay without sexual
      life(chi2=70.445, P<0.05), erectile function during audio-video sexual
      stimulation(chi2=34.422, P<0.05), etc. But in both groups, some patients didn't
      have masturbation so that they couldn't answer the masturbation questions.
      CONCLUSION: We have created a new conception about the patients without sexual
      life, erectile dysfunction-no sexual life, which defines it as the inability to
      have enough erection hardness and duration so as to have enough confidence in
      attempting sexual intercourse for more than six months. We will establish a
      special index of the ED-NS questionnaire to assess erectile function of ED-NS.
      Further study is needed.

PMID- 21844973
TI  - [Age-specific reference ranges for prostate specific antigen in 16 222 Chinese
      men].
AB  - OBJECTIVE: To investigate the PSA level of 16 222 asymptematic men in Shenzhen
      who came from different areas of China, in order to find out the PSA levels of
      Chinese men. METHODS: Serum samples of 16 222 men who came to Peking University
      Shenzhen Hospital for health examination were collected, all of whom had no
      symptoms. Their serum PSA levels were measured with MEIA with ILMA instrument.
      RESULTS: The mean PSA level of the 16 222 men in our research was 0.986 MUg/L,
      and the standard deviation was 1.190. The 95% percentile was 2.375 MUg/L. Of all
      the cases ,the 95% percentile of 15 498 was lower than 2.5 MUg/L, about
      95.472%;that of 699 was between 2.5-10.0 MUg/L, about 4.306%;And if took 4.0
      MUg/L as reference value,that of 15 948 cases was below 4.0 MUg/L, about
      98.244%;that of 249 was between 4.0-10.0 MUg/L, about 1.534%;That of only 36
      cases was greater than 10.0 MUg/L, about 0.222%;The 95% percentiles of the
      different age groups were: 10-19 years 0-1.067 MUg/L;20-29 years 0-1.818 MUg/L;30
      39 years 0-1.914 MUg/L;40-49 years 0-2.001 MUg/L;50-59 years 0-2.900 MUg/L;60-69
      years 0-5.862 MUg/L;70-79 years 0-8.536 MUg/L;elder than 80 years 0-12.869
      MUg/L;There were statistic differences between thedifferent age groups.
      CONCLUSION: Our data demonstrate that the mean value of PSA levels of Chinese men
      is 0.986 MUg/L at present stage, and the 95% percentile is 2.375 g/L. Our PSA
      levels of each age group are different from Oesterling's reference values which
      are commonly accepted in the world. The PSA level of Chinese men who are under 60
      years is lower than that of Euramericans, while the PSA level of Chinese men who
      are above 60 years is higher than that of Euramericans. This shows that for the
      men who are under 60 the reference value should be 2.5 MUg/L, while for the men
      who are above 60, we could still use 4 MUg/L as reference value.

PMID- 21844974
TI  - [Investigation on physiological characteristics in "offspring of Lop Nor
      people"].
AB  - OBJECTIVE: To investigate the physiological characteristics in "offspring of Lop
      Nor people", a special population from the Lop Nor dried up in Xinjiang. METHODS:
      A total of 594 subjects were selected by convenience sampling method from Yuli
      County, Xinjiang Uygur Autonomous Region. All data were obtained from each person
      by the questionnaire and standard physical examinations. RESULTS: The prevalence
      of hypertension for "offspring of Lop Nor people" was 47.1% for males and 45.4%
      for females, respectively. The prevalence of high body mass index (BMI>=28
      kg/m(2)) was higher in females than that in males, with 41.2% vs. 32.7%. The
      prevalence of abnormal TG in males was higher than that in females, 36.6% vs.
      25.5% (P=0.003 7). And prevalence of abnormal HDL in males was higher than that
      in females, 9.7% vs. 3.9% (P=0.003 8). The results of multivariate analysis
      revealed that BMI and TG were the risk factors for hypertension in "offspring of
      Lop Nor people" . CONCLUSION: The preliminary results show that the main
      physiological characteristics are high blood lipid, high prevalence of
      hypertension and obesity in "offspring of Lop Nor people". High blood lipid and
      obesity might be the main risk factors for hypertension in this population.

PMID- 21844975
TI  - [Levels of interlukin-6 and tumor necrosis factor-alpha in saliva of patients
      with type 2 diabetes mellitus and oral lichen planus].
AB  - OBJECTIVE: To study the relationship between type 2 diabetes mellitus (T2DM) and
      oral lichen planus (OLP) by detecting the level of salivary tumor necrosis factor
      (TNF-alpha) and interlukin-6 (IL-6). METHODS: Subjects were divided into 4
      groups: T2DM/OLP group 29 patients, T2DM group 39 patients, OLP group 21
      patients, and control group 43 individuals. The salivary interleukin-6 (IL-6) and
      tumor necrosis factor (TNF-alpha) were detected by enzyme-linked immuno sorbent
      assay (ELISA). RESULTS: (1) The level of salivary IL-6 in patients with T2DM/OLP
      [(12.30 +/- 16.03) ng/L] was significantly higher than those in T2DM [(6.29 +/-
      5.91) ng/L] and OLP groups [(3.64 +/- 4.47) ng/L], P<0.05. The level of salivary
      IL-6 was significantly lower in OLP group [(3.64 +/- 4.47) ng/L] than in control
      group [(7.91 +/- 4.05) ng/L], P<0.001. The level of salivary TNF-alpha in T2DM
      group [(8.80 +/- 8.41) ng/L] was significantly lower than those in OLP [(14.02 +/
      9.65) ng/L] and control groups [(15.02 +/- 6.13) ng/L], P<0.05. (2) The level of
      salivary TNF-alpha is significantly negative correlated with pH value of saliva
      in T2DM/OLP group(r=-0.593, P<0.01);The level of salivary TNF-alpha and IL-6 are
      significantly positive correlated with waistline in control
      group(r=0.312,P=0.05).(3) The levels of salivary IL-6 and TNF-alpha were
      positively related to OLP clinical type, P<0.05. (4)When OLP played an overlying
      role on T2DM, the level of TNF-alpha was weakened and that of IL-6 was
      strengthened. CONCLUSION: When T2DM and OLP are in concurrence,there is a
      synergistic effect,and the secretion of IL-6 increases markedly; The level of
      salivary TNF-alpha is associated with local oral environment.

PMID- 21844976
TI  - [Correlation between the quantity of oral mucosal micronucleus cells and
      cancerization].
AB  - OBJECTIVE: To explore the relationship between micronuclei and malignant
      development of oral epithelial dysplasia (OED). METHODS: Oral exfoliated cells
      were smeared from 30 control subjects, 46 patients with oral lichen planus (OLP),
      78 patients with oral leukoplakia (OLK) and hyperplasia, 30 patients with OLK and
      mild OED, 29 patients with OLK and moderate OED, 15 patients with OLK and severe
      OED and 22 patients with oral squamous cell carcinoma (OSCC). RESULTS:
      Micronucleus rates declined according to the order of OSCC, OLK and severe OED,
      OLK and moderate OED, OLK and mild OED, OLK and hyperplasia, OLP and control
      groups (P<0.001). CONCLUSION: Micronuclei may reflect the progression of oral
      epithelial malignant changes. It could be used in monitoring cancerization in
      following up cases regularly.

PMID- 21844977
TI  - [Diagnosis and treatment of complicated deep infiltrated endometriosis: a case
      report and literature review].
AB  - OBJECTIVE: To explore diagnostic and therapeutic methods of patients with deep
      infiltrating endometriosis. METHODS: Clinical data of a case of complicated deep
      infiltrating endometriosis were analyzed retrospectively. RESULTS: A 39-year-old
      female patient with deep infiltrating endometriosis involving the cervix,
      bilateral parametrium, uterosacral ligaments, left ureter, left ovary, pouch of
      Douglas, rectovaginal septum, and vagina, presented as the advanced cervical
      cancer. She went through initial manifestation of hypogastralgia, irregular
      vaginal bleeding and left hydronephrosis. Cervical biopsy and embolism of
      bilateral uterine artery, cervical conization and laparoscopic approach and
      biopsy confirmed the diagnosis. After being treated with gosereline acetate for
      three months, she received a radical removal and ureterolysis. She had no
      evidence of recurrence after two years' follow-up. CONCLUSION: When gynecologists
      make a differential diagnosis of the cervical malignancy, if the clinical
      manifestations are inconsistent with histopathologic examination, possibility of
      deep infiltrating endometriosis should be considered and diagnosed by
      histopathologic examination.

PMID- 21844978
TI  - [Safety of early cardiopulmonary exercise test in myocardial infarction patients
      with acute ST-elevation].
AB  - OBJECTIVE: To investigate the safety of cardiopulmonary exercise testing (CPET)
      early after acute ST-elevation myocardial infarction (STEMI). METHODS: We
      retrospectively reviewed 302 patients who underwent CPET early after STEMI in a
      single exercise laboratory. Demographic data, presence of concomitant diseases,
      characteristics of AMI, angiography findings and the safety of CPET were
      evaluated. RESULTS: 41.7% of the tests were reported to have stopped earlier than
      expected. The most common limiting symptoms were generalized fatigue (67.5%).
      None of the tests terminated because of severe arrhythmia, syncope or sudden
      death. In contrast to patients with incomplete revascularization (IR), the rate
      of stopping earlier than expected was lower in complete revascularization (CR)
      patients (35.1% vs. 49.6%, P=0.040). After being adjusted by the subjects'
      demographic features, clinical characteristics and cardiovascular risk factors,
      IR (P=0.013, OR=1.869, 95%CI 1.139 to 3.067) and left ventricular end-diastolic
      dimension (LVEDD, P=0.018, OR=1.064, 95%CI 1.011 to 1.121) were independent risk
      factors for the limiting symptoms of CPET. CONCLUSION: The experience of this
      laboratory shows that CPET is relatively safe in patients early after STEMI. IR
      and LVEDD are independent risk factors for the limiting symptoms of CPET.

PMID- 21844979
TI  - [Results of long-time follow up of patients who survived more than 5 years after
      liver transplantation: a single center experience].
AB  - OBJECTIVE: To investigate liver transplantation patients who survived for more
      than 5 years for the occurrences of their various long-term complications,
      prevention and treatment. METHODS: By May 31, 2010, totally 69 patients who had
      received liver transplantation from July 2000 to May 2005 in Peking University
      People's Hospital were still alive. We reviewed the clinical data of these
      patients and the recent records of their liver and kidney functions, blood
      pressure, blood sugar and blood fat, etc. The occurrences of their various long
      term complications were summarized and the status of treatment was studied.
      RESULTS: In these 69 patients, 39.1% (27/69) of them were overweight or obese,
      33.3% (23/69) had post transplantation diabetes mellitus (PTDM), 26.1% (18/69)
      had hyperlipemia, 20.3% (14/69) suffered from renal insufficiency, 15.9% (11/69)
      had hypertension and 23.2% (16/69) had hyperuricemia. Interestingly, the
      occurrences of PTDM and hyperlipemia in overweight or obese patients were higher
      than those in normal weight patients (48.2% vs. 23.8% and 40.7% vs. 16.7%,
      P<0.05). In addition, hepatitis B virus (HBV) infection recurred in 4 patients
      out of the 61 patients who had HBV related liver disease pre-operation, and liver
      cancer relapsed in 3 patients out of the 19 patients who had hepatocellular
      carcinoma (HCC) pre-operation. Totally 4 patients received re-transplant during
      the follow-up. CONCLUSION: The occurrences of long-term complications in liver
      transplantation patients who survived for more than 5 years were rather high, so
      the follow-up should be strengthened and procedures done to avoid the
      exacerbation of these complications.

PMID- 21844980
TI  - [Comparison of new portable home electronic uroflowmeter with Laborie
      uroflowmeter].
AB  - OBJECTIVE: To design a new portable home electronic uroflowmeter and compare it
      with traditional methods. METHODS: The system consists of collectors, urine
      conducting apparatus, intelligent cell phone, wireless network communication
      technology, computer analysis and drawing, and data storage technology, etc., and
      can automatically collect voiding information from patients with lower urinary
      tract symptoms(LUTS) Through Bluetooth, the voiding information was sent to the
      patient's intelligent cell phone from the collector, then stored directly by
      intelligent cell phone and wirelessly transmitted to the workstation in hospital.
      The system was primarily tested with regard to accuracy of measurement of the
      voided volume. Multiple doses with known volume were introduced in the system and
      Laborie uroflowmeter. Furthermore, 38 outpatients who had LUTS were tested
      simultaneously with the system and Laborie uroflowmeter. The statistical method
      for assessing agreement between the two methods of clinical measurement was Bland
      Altman analysis. Among the subjects, there were 22 male patients and 16 female
      patients, ranging from 21 to 37 years old, with an average age of 25.5 years, of
      whom, 19 were tested once and 19 patients twice, equaling to 57 tests. RESULTS:
      The system could accurately collect and analyze voiding time, uroflowmetry,
      voided volume, and automatically provide uroflowmetry parameters. The measurement
      error of 100, 200, 300, 500 and 800 mL is less than 5%. 12.28%, 5.26% and 3.51%
      of the Qmax, Qave and voided volume points were beyond the 95% limits of
      agreement. The maximum absolute values of the Qmax, Qave and voided volume
      difference were 0.38 mL/s, 0.70 mL/s and 2.90 mL, respectively.They agreed with
      the recommendation of Standardization International Continence Society.
      CONCLUSION: The new portable home electronic uroflowmeter has good agreement with
      Laborie uroflowmeter,and is a new LUTS monitoring system integrated with correct,
      reliable, real-time, convenient and easy-managing advantages. It is as
      noninvasive and reliable as traditional methods, and its portable feature
      facilitates application out of hospitals. It can also record voiding diaries.

PMID- 21844981
TI  - [Malakoplakia of the prostate: a case report].
AB  - Malakoplakia of the prostate is a rarely reported granulomatous inflammatory
      disorder which may clinically mimic carcinoma of the prostate gland. This paper
      reported 1 case of malakoplakia of the prostate which was successfully diagnosed
      with the use of transrectral ultrasound and ultrasound-guided needle biopsy, and
      the cases and related articles were reviewed. The patient was successfully cured
      by the use of compound sulfamethoxazole tablet (SMZ-TMP) at the same time.
      Histologic examination is required to make the correct diagnosis. Biopsy of the
      prostate and antibiotics should be used clinically.

PMID- 21844982
TI  - [Treatments of erectile dysfunction combined with lower urinary tract symptoms
      associated with benign prostatic hyperplasis].
AB  - Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS)
      and erectile dysfunction (ED) are common conditions seen in aging males. Although
      the exact mechanism of ED combined BPH/LUTS is unknown, treatment with alpha
      adrenergic receptor resistance agents (alpha-ARAs) contributes to some
      improvement in ED, and phosphodiesterase-5 inhibitors (PDE-5I) are also of
      benefit to BPH/LUTS. The action mechanisms of these medications support these
      observed benefits, which are being studied in the basic science and clinical
      settings. Much remains to be investigated, but it is clear that the associations
      between BPH/LUTS and ED lay the foundation for future therapies and possible
      preventative strategies. This article has mainly summarized the advancement of
      epidemiology, basic research and treatment of ED combined with BPH/LUTS with
      alpha-receptor blockers and phosphodiesterase-5 inhibitors.

PMID- 21844983
TI  - [Ketamine-associated urinary tract damage].
AB  - Ketamine is widely used as an anesthetic during surgical procedures in both
      animals and humans. As its unique effects of inducing the dissociative
      hallucinatory,vivid dreams, out-of-body experiences, and delirium, it has
      diverted from legitimate uses to the illicit drug market, and abusing ketamine
      has become a serious social problem. The abusers may use ketamine alone or mixe
      it with other drugs to get an intense pleasure. There are case reports from all
      over the world in recent years that abusing ketamine may induce severe lower
      urinary tract symptoms (LUTS), and a variety of anatomical and functional lesions
      can be found in the urinary tract if further examinations are administrated.
      There is no universally recognized treatment protocols for this syndrome.
      Ketamine cessation or even reduction is the most effective treatment to prevent
      deterioration of the urinary tract, and intravesical instillation of hyaluranic
      acid (cystitstat) and oral pentosan polysulphate (elmiron) may take effect. The
      pathogenesis of ketamine-associated urinary tract destruction is unclear, and
      further study is needed.

PMID- 21844984
TI  - [Prevention and management of erectile dysfunction after laproscopic radical
      prostatectomy].
AB  - Radical prostatectomy remains the standard treatment for men with clinically
      localized prostate cancer. Erectile dysfunction (ED) is a common complication for
      patients who underwent radial prostaectomy (RP). The incidence of ED after RP
      varies dramatically between 20%-90%. With the introduction of nerve-sparing
      technique in RP and penile rehabilitation in early period after RP, erectile
      function can be preserved in many patients. This article reviews the prevention
      and management of erectile dysfunction after laproscopic radical prostatectomy.

PMID- 21844985
TI  - Use the Correlation Coefficient to Summarize Regression Performance?
AB  - The correlation coefficient is commonly used to indicate the quality of fit in
      regression. This practice is questionable.

PMID- 21844986
TI  - The promise of phytoestrogens.

PMID- 21844987
TI  - Non-inferiority clinical trials: Practical issues and current regulatory
      perspective.
AB  - Non-inferiority clinical trials are being performed with an increasing frequency
      now-a-days, because it helps in finding a new treatment that have approximately
      the same efficacy, but may offer other benefits such as better safety profile.
      Non-inferiority clinical trials aim to demonstrate that the test product is no
      worse than the comparator by more than a pre-specified small amount. There are
      several fundamental differences between non-inferiority and superiority trials.
      Some practical issues concerning the non-inferiority trials are assay
      sensitivity, choice of the non-inferiority margin, sample size estimation, choice
      of active-control, and analysis of non-inferiority clinical trials. For serious
      infections such as hospital-acquired bacterial pneumonia/ventilator-associated
      bacterial pneumonia, community-acquired bacterial pneumonia, and acute bacterial
      skin and skin structure infections, the United States Food and Drug
      Administration (US FDA) has recently recommended that it is possible to define a
      reliable and consistent estimate of the efficacy of active treatment relative to
      placebo from available data, which can serve as the basis for defining a new
      inferiority margin for an active-controlled, non-inferiority trial. But for some
      indications with a high rate of resolution without antibacterial drug therapy
      such as acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic
      bronchitis (ABECB), and acute bacterial otitis media (ABOM), the US FDA has
      recommended that the available data will not support the use of a non-inferiority
      design and other trial designs (i.e., superiority designs) should be used to
      provide the evidence of effectiveness in these three indications.

PMID- 21844988
TI  - A brief review on recent developments in animal models of schizophrenia.
AB  - Number of patients suffering from schizophrenia is increasing daily,
      subsequently, increasing the need of proper medication to treat the symptoms and
      eventually improve the patients' condition. However, all the progress for
      designing or discovering medication comes to a standstill, as the symptomatic
      treatment can only be done in the patients, but performing clinical trials with
      all the possible candidate drugs in human beings and patients is unethical. Thus,
      the need arises for proper animal and non-human primate animal models of the
      disease, which would not only serve the purpose of understanding the disease in a
      better physiological setting, but also would allow the scientists to focus on
      developing a therapeutically effective and potent medication for treating this
      hazardous disease. This brief review article focuses on a few animal models which
      are generally used for carrying out studies on schizophrenic symptoms in research
      labs and industry worldwide. The paper also tries to validate the pre-clinically
      available models based on certain specified criteria like the predictive
      constructive and face validity. Thus, the paper gives guidance toward the
      mechanistic and traditional models of schizophrenia applying some of the newer
      principles and helps researchers in deciding a particular relevant model for
      their own purpose.

PMID- 21844989
TI  - Effect of information, education and communication intervention on awareness
      about rational pharmacy practice in pharmacy students.
AB  - BACKGROUND: There is a growing indifference among the pharmacy practitioners
      towards their duty as information providers to the patients. The patients do not
      always get enough desired information about proper use of medicines from the
      prescribers also. This contributes to improper use of medicines by the patients.
      OBJECTIVES: To bring about awareness about rational pharmacy practice in pharmacy
      students for better service to the patients. MATERIAL AND METHODS: The final year
      students of Bachelor of Pharmacy (B. Pharm) from four colleges of Nagpur were
      enrolled for the study after informed consent. Their base knowledge was assessed
      through a written test which comprised of 27 objective questions related to
      rational pharmacy practice. This was followed by a series of seven articles on
      rational medicine use, published in leading local English news daily. The
      participants were reminded to read them on the day of publication of each
      article. As a backup, the articles were displayed on the notice board of
      respective colleges. Second intervention was a half day interactive session where
      series of six lectures were delivered to the participants on the right and wrong
      approaches in pharmacy practice. Posters about the do's and dont's of rational
      pharmacy practice were also displayed at the venue. The session was followed by a
      repeat test using the same pre-test to assess the change. Pre and post
      intervention data was compared using Fisher's Exact test. RESULTS: It was
      observed that the intervention did bring about a positive change in the attitude
      and knowledge of the final year Pharmacy students about rational pharmacy
      practice. DISCUSSION: The role of a pharmacist in health care provision is
      usually overlooked in India. Hence there is strong need for reinforcement in
      final year B. Pharm when most of the students go in for community service. Such
      interventions will be helpful in bringing about a positive change towards
      rational practice of pharmacy. CONCLUSION: This study showed that a properly
      timed and meticulously implemented intervention brings about a positive change in
      the attitude and knowledge of pharmacy students.

PMID- 21844990
TI  - Tacrolimus and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: An
      interaction study in CYP3A5 non-expressors, renal transplant recipients.
AB  - OBJECTIVES: Atherosclerosis is a significant factor affecting long-term outcome
      in renal transplant recipients. Studies have been conducted to determine the
      pharmacogenomic pathways involved in statin efficacy, efficiency, and adverse
      effect likelihood. However, little is known about the influence of statins on
      tacrolimus kinetics. The aim of this study was to investigate possible
      pharmacological interactions between tacrolimus and statins in CYP3A5 non
      expressors, renal transplant recipients. MATERIALS AND METHODS: Twenty-four
      patients, treated with tacrolimus (n=24), methylprednisolone (n=24), and
      mycophenolate mofetil (n=19)/azathioprine (n=1)/everolimus (n=4), participated in
      the study. After an observation time of 112+/-36 days, statins, namely,
      atorvastatin (n=12), simvastatin (n=8), pravastatin (n=2), or fluvastatin (n=2),
      were administered for additional 101+/-34 days. DNA was extracted from whole
      blood sample and polymerase chain reaction followed by restriction fragment
      length polymorphism analysis was used for CYP3A5 genotyping. Student's t-test and
      Mann-Whitney test were used to test the significance of difference in variables
      that passed or did not pass Kolmogorov's normality test, respectively. RESULTS:
      No statistically significant difference was observed in tacrolimus daily dose,
      concentration, concentration/dose ratio, and volume of distribution before and
      during the administration of statins. Statistically significant decrease in serum
      cholesterol was observed after initiation of statins. Renal and hepatic function
      remained unchanged and no skeletal muscle abnormalities were reported.
      CONCLUSIONS: The results of this study show that tacrolimus and statins do not
      interact in terms of efficacy, efficiency, and adverse effect likelihood. No
      significant clinical interaction or effect was observed, even with the use of
      atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus.

PMID- 21844991
TI  - Effect of imatinib on the biochemical parameters of the reproductive function in
      male Swiss albino mice.
AB  - BACKGROUND: Treatment of cancers with cytotoxic agents such as tyrosine kinase
      inhibiting drugs often, but not always, result in transient to permanent
      testicular dysfunction. Germ cells are important targets of many chemicals. Most
      of the drugs are genotoxins and induce irreversible effect on genetic makeup.
      These mutagenic changes are proportionally related to carcinogenesis. This is
      alarmingly dangerous in youth and children, since these effects last longer,
      affecting fertility or forming basis for carcinogenesis. There is paucity of
      reports on planned studies of imatinib on the testicular function. Hence, the
      study was planned to assess the effects of imatinib on biochemical markers of
      testicular functions in male Swiss albino mice. MATERIALS AND METHODS: Male Swiss
      albino mice were treated with imatinib and sacrificed at the end of first,
      second, fourth, fifth, seventh, and tenth week after the last exposure to
      imatinib. The testis were removed, weighed, and processed for biochemical
      analysis. RESULTS: The intratesticular testosterone level was significantly
      (P<0.001) reduced in treated groups and severe effect was observed on week 4 and
      5. The intratesticular lactate dehydrogenase (LDH) level was significantly
      increased by imatinib in all treated groups up to week 5. CONCLUSION: Imatinib
      does affect testosterone and LDH level significantly, but this effect is
      reversible once the drug is withdrawn. This finding may help the clinicians to
      plan and address the fertility-related issues in young patients of reproductive
      age who are being treated with imatinib for gastrointestinal tumors and chronic
      myeloid leukemia.

PMID- 21844992
TI  - Evaluation of the anti-inflammatory activity of Aegle marmelos (Bilwa) root.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to evaluate and compare the
      anti-inflammatory activity of the aqueous root bark extract of Aegle marmelos
      (Bilwa) in experimental acute and chronic inflammatory animal models. MATERIALS
      AND METHODS: Aqueous extract of root bark of Bilwa was prepared and tested for
      anti-inflammatory activity in albino rats weighing 150-280 grams. The animals
      were randomly divided into 3 groups of 6 each; one group served as control and
      other two groups received indomethacin and Bilwa orally 1 hour prior to
      experimentation. The in vivo anti-inflammatory activity was studied using the
      acute (Carrageenan induced paw edema) and chronic (Cotton pellet induced
      granuloma) animal models. Anti-inflammatory activity was expressed as Percent
      inhibition (PI). Statistical analysis was performed using One-way analysis of
      variance (ANOVA) followed by Scheffe's post hoc test. P < 0.05 was considered
      statistically significant. RESULTS: The PI with indomethacin and Bilwa in
      carrageenan induced paw edema were 52.7% and 46% and in cotton pellet induced
      granuloma were 24.7% and 9.2% respectively. Indomethacin showed highly
      significant anti-inflammatory activity in both the models. However, Bilwa showed
      highly significant activity in acute model and but a trend of anti-inflammatory
      activity in chronic model studied. CONCLUSIONS: As Bilwa showed significant anti
      inflammatory activity in the models studied, it can be a promising anti
      inflammatory agent.

PMID- 21844993
TI  - Managing diabetic ketoacidosis in non-intensive care unit setting: Role of
      insulin analogs.
AB  - AIM: To compare the efficacy and safety of rapid acting insulin analog lispro
      given subcutaneously with that of standard low-dose intravenous regular insulin
      infusion protocolin patients with mild to moderate diabetic ketoacidosis.
      MATERIALS AND METHODS: In this prospective, randomized and open trial, 50
      consecutive patients of mild to moderate diabetic ketoacidosis were randomly
      assigned to two groups. The patients in group 1 were treated with intravenous
      regular insulin infusion and admitted in intensive care unit. The patients in
      group 2 were treated with subcutaneous insulin lispro 2 hourly and managed in the
      emergency medical ward. Response to therapy was assessed by duration of treatment
      and amount of insulin administered until resolution of hyperglycemia and
      ketoacidosis, total length of hospital stay, and number of hypoglycemic events in
      the two study groups. RESULTS: The baseline clinical and biochemical parameters
      were similar between the two groups. There were no differences in the mean
      duration of treatment and amount of insulin required for correction of
      hyperglycemia and ketoacidosis. There was no mortality and no difference in the
      length of hospital stay between the two groups. The length of stay and amount of
      insulin required for correction of hyperglycemia was greater in patients who had
      infection as the precipitating cause than those with poor compliance. The
      hypoglycemic events were higher in the regular insulin group (2 vs1) than in the
      lispro group. CONCLUSION: Patients with uncomplicated diabetic ketoacidosis can
      be managed in the medical wards with appropriate supervision and careful
      monitoring. Rapid acting insulin analog lispro is a safe and effective
      alternative to intravenous regular insulin for this subset of patients.

PMID- 21844994
TI  - A biochemical study on the gastroprotective effect of hydroalcoholic extract of
      Andrographis paniculata in rats.
AB  - AIM: The aim of the present study is to evaluate the gastroprotective effect of
      hydroalcoholic extract of Andrographis paniculata (HAEAP) in male albino wistar
      rats. MATERIALS AND METHODS: Rats were pretreated with HAEAP (100,200,500mg/kg b.
      wt for 30 days) and then gastric ulcers were induced by ethanol, aspirin, pylorus
      ligation and cold restraint stress models. Ulcer score was determined in all the
      ulcer models. pH, gastric volume, titrable acidity, pepsin, mucin,
      myeloperoxidase, H(+)K(+)ATPase, thiobarbituric acid reacting substances (TBARS)
      and antioxidant enzyme activities were assayed in ethanol-administered rats.
      RESULTS: The ulcer score was found to be low in HAEAP-pretreated rats. Among the
      doses studied, 200 mg/kg b.wt was found to be optimum for significant ulcer
      reduction. The test drug significantly reduced the acidity, pepsin concentration,
      myeloperoxidase and H(+)K(+)ATPase activities in ethanol-administered rats. The
      elevated TBARS and decreased glutathione (GSH) and mucin levels observed during
      ulcerogenesis were found to be altered in HAEAP-received animals. CONCLUSIONS:
      The ulcer preventing effect of HAEAP may partly be due to its regulating effect
      on H(+)K(+)ATPase activity and /or mucin preserving effects. The flavonoids
      present in the HAEAP might be responsible for the gastroprotective action
      probably by maintaining the antioxidants and thiol status in the gastrointestinal
      tract.

PMID- 21844995
TI  - Nanotechnology in oncology: Characterization and in vitro release kinetics of
      cisplatin-loaded albumin nanoparticles: Implications in anticancer drug delivery.
AB  - CONTEXT: Nanotechnology is an empowering technology that holds promise in cancer
      therapeutics by increasing the ratio of tumor control probability to normal
      tissue complication probability. It can increase the bioavailability of the drug
      at the target site, reduce the frequency of administration and reach otherwise
      lesser-accessible sites. The present study shows the feasibility of the cisplatin
      loaded albumin nanoparticle as a sustained delivery system. AIMS: Cisplatin is
      one of the most widely used chemotherapeutic agents for the treatment of
      malignant disorders. Conventional cisplatin formulation given as intravenous
      infusion has low bioavailability to the target organ in addition to significant
      side-effects, like ototoxicity and nephrotoxicity. The aim of this study was to
      develop a protein-based nanoparticulate system for sustained release of
      cisplatin. MATERIALS AND METHODS: Nanoparticles were prepared by the coacervaton
      method of microcapsulation and chemical cross-linking with glutaraldehyde.
      Particle size was characterized by dynamic light scattering and transmission
      electron microscopy. RESULTS AND CONCLUSIONS: Using the coacervation method,
      nanoparticles of less than 70 nm diameter were produced. Drug encapsulation
      measured by ultraviolet spectroscopy varied from 30% to 80% for different ratios
      of cisplatin and protein. In vitro release kinetics shows that the nanoparticle
      based formulation has biphasic release kinetics and is capable of sustained
      release compared with the free drug (80% release in 45 h). The study proves the
      feasibility of the albumin-based cisplatin nanoparticle formulation as a
      sustained release vehicle of cisplatin.

PMID- 21844997
TI  - Fertility, developmental toxicity and teratogenicity in albino rats treated with
      methanol sub-fraction of Carica papaya seeds.
AB  - OBJECTIVE: To evaluate the status of fertility, developmental stages during
      gestation and teratological changes, if any, following oral administration of
      methanol sub-fraction (MSF) of the benzene chromatographic fraction of the
      chloroform extract of the seeds of Carica papaya in rats. MATERIALS AND METHODS:
      The MSF was administered at the doses of 50 mg contraceptive dose (CD), 100 mg
      (2* CD), 250 mg (5* CD) and 500 mg (10* CD)/kg body wt/day along with vehicle
      treated control using 10 male and 20 female Wistar rats in each group. Necropsies
      were performed one day before the expected parturition. Status of gravid/non
      gravid uterus, the number of corpora lutea in the ovary, implantation status,
      fetal wellbeing, fetal resorption, fetal body weight, external, visceral and
      skeletal malformations were recorded. RESULTS: Pregnancies were recorded in
      vehicle-treated control animals and in the animals treated with 50 mg/kg body
      wt/day. The animals treated with 2* CD, 5* CD and 10* CD did not get pregnant.
      The fetuses and the status of the ovary, uterus and implantation, fetal body
      weight, soft tissues and skeletal structures were recorded normal. Data were
      comparable to those of control. CONCLUSION: The results suggest that the test
      substance had no developmental toxicity and teratogenicity which could affect
      pregnancy, implantation and gestation.

PMID- 21844996
TI  - Protective effects of Phyllanthus amarus aqueous extract against renal oxidative
      stress in Streptozotocin -induced diabetic rats.
AB  - AIM AND OBJECTIVES: In the present study, we have evaluated the
      antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of
      Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats.
      MATERIALS AND METHODS: PAAEt was administered at 200 mg/kg body weight/day to
      normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by
      gavage for eight weeks. During the experimental period, blood was collected from
      fasted rats at 10 days intervals and plasma glucose level was estimated. The
      plasma lipid profile was estimated at the end of experimental period. After the
      treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced
      glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione
      reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST),
      catalase (CAT) and superoxide dismutase (SOD) were also assayed. RESULTS: The
      significant decrease in the body weight, hyperglycemia and hyperlipidemia
      observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt
      treatment in diabetic treated group (DT-group). D-group rats showed increased
      renal oxidative stress with increased LPO and protein oxidation. DT-group showed
      a significant decrease in renal LPO, protein oxidation and a significant increase
      in GSH content and GR, GPx and GST activities when compared with D-group. The
      activities of SOD and CAT decreased significantly in D-group, but were normalized
      in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant
      decrease in lipid profile, renal LPO and protein oxidation, with significant
      increase in renal GSH and activities of antioxidant enzymes compared to normal
      rats (N-group). CONCLUSION: Our results demonstrated that PAAEt with its
      antidiabetic, hypolipidemic and antioxidant properties could be a potential
      herbal medicine in treating diabetes and renal problems.

PMID- 21844998
TI  - Influence of Momordica charantia on oxidative stress-induced perturbations in
      brain monoamines and plasma corticosterone in albino rats.
AB  - OBJECTIVES: The objective of this study was to evaluate the antistress activity
      of Momordica charantia (MC) fruit extract on stress-induced changes in albino
      rats and also to explore attenuating effects of MC on in vitro lipid peroxidation
      in rat brain. MATERIALS AND METHODS: In this study, Wistar albino rats (180-200
      g) were used. Plasma corticosterone and monoamines-5-hydroxy tryptamine (5-HT),
      norepinephrine (NE), epinephrine (E) and dopamine (DA) in cortex, hypothalamus
      and hippocampus regions of brain were determined in animals under different
      stressful conditions. Ethanolic fruit extract of MC, at doses of 200 and 400
      mg/kg, was used. The oxidative stress paradigms used in in vivo models were acute
      stress (AS) and chronic unpredictable stress (CUS). Panax quinquefolium (PQ) was
      used as a standard in in vivo models and ascorbic acid was used as a reference
      standard in the in vitro method. RESULTS: Subjecting the animals to AS
      (immobilization for 150 min once only) resulted in significant elevation of
      plasma corticosterone levels and brain monoamine levels. Pretreatment with MC at
      doses of 200 and 400 mg/kg p.o. significantly countered AS-induced changes and a
      similar effect was exhibited by PQ at 100 mg/kg p.o. In the CUS regimen
      (different stressors for 7 days), plasma corticosterone levels were significantly
      elevated whereas the levels of 5-HT, NE, E, and DA were depleted significantly.
      Pretreatment with MC (200 and 400 mg/kg) attenuated the CUS-induced changes in
      the levels of above monoamines in cortex, hypothalamus, and hippocampus regions
      of brain and plasma corticosterone in a dose-dependent manner. Furthermore, MC
      extract (1000-5000 MUg/mL) exhibited a significant quenching effect on in vitro
      lipid peroxidation indicating its strong antioxidant activity which was compared
      with ascorbic acid. CONCLUSIONS: This study reveals the antistress activity of MC
      as it significantly reverted the stress-induced changes, and the activity might
      be attributed to its antioxidant activity since stress is known to involve
      several oxidative mechanisms.

PMID- 21844999
TI  - Comparison of the effect of vanadium and deferoxamine on acetaminophen toxicity
      in rats.
AB  - AIM: Acetaminophen (APAP) can change to toxic metabolites at high dose; if these
      metabolites are in high amounts, the body will be unable to neutralize them, and
      several tissues including liver will be damaged. In the present study, the effect
      of vanadium was compared with deferoxamine on hepatotoxicity and also kidney
      function during APAP administration in rats. MATERIAL AND METHODS: The study was
      done in 5 groups (5 rats in each group): group I to V, respectively, received
      normal saline, APAP, APAP + deferoxamine, APAP + vanadium, and vanadium. At the
      end of the study, blood was collected and serum was separated for laboratory
      tests. The serum levels of alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), blood urea nitrogen (BUN), creatinine, sodium, and
      potassium were determined. The liver of the rats were separated for tissue
      processing and light microscopic examination. RESULTS: APAP significantly
      increased; ALT level and deferoxamine and vanadium prevented its elevation. Also,
      deferoxamine and vanadium prevented increase of AST by APAP. The change of
      factors, which are related to the kidney function, i.e., BUN, creatinine, sodium,
      and potassium were not considerable. CONCLUSION: Thus, it was observed that
      vanadium had better effect than deferoxamine in the prevention of hepatotoxicity
      induced by APAP.

PMID- 21845000
TI  - Antidiabetic and vasoprotective activity of lithium: Role of glycogen synthase
      kinase-3.
AB  - OBJECTIVES: Lithium is a drug of choice in maniac disorder. Lithium inhibits the
      glycogen synthase kinase-3 (GSK-3), an enzyme involved in the insulin signalling
      pathway. Elevated levels of GSK-3 were found in diabetic rats and humans. We
      aimed to determine the effect of lithium chloride in diabetes and associated
      vascular complications in diabetic rats. MATERIALS AND METHODS: Type 2 diabetes
      was induced by high fat diet and low dose of streptozotocin. Diabetic rats were
      divided into diabetic control and lithium chloride treatment groups. Lithium
      chloride was used as a GSK-3 inhibitor. The treatment was given for 4 weeks.
      Various biochemical parameters were measured before initiation and the end of
      treatment. Systolic blood pressure was measured by the non-invasive tail-cuff
      method, while various biochemical and tissue parameters were estimated for
      efficacy. Vasoreactivity was performed by taking the contractile response of
      H(2)O(2) (10(-6) M to 10(-3)M) and angiotensin II (10(-11) to 10(-7) M) in rat
      thoracic aortas of different groups. Statistical comparisons between all groups
      were performed by using two tailed one-way ANOVA followed by the Dunnett test. P
      values <0.05 were considered statistically significant. RESULTS: Treatment with
      lithium chloride significantly reduced the augmented systolic blood pressure,
      various biochemical parameters, and antioxidant parameters in diabetic-treated
      rats. Treatment also showed the decrease in augmented responses of H(2)O(2) and
      angiotensin II in rat thoracic aortas of treated rats. CONCLUSIONS: We can
      conclude that lithium chloride treatment reduces the diabetic state as well as
      diabetes-induced vascular dysfunction.

PMID- 21845001
TI  - Comparison of nebivolol and atenolol on blood pressure, blood sugar, and lipid
      profile in patients of essential hypertension.
AB  - BACKGROUND: Nebivolol is a third-generation beta-blocker, with highest beta(1)
      selectivity and nitric-oxide-derived vasodilatation. It also exhibits
      antiproliferative and antioxidant property that has beneficial metabolic profile
      compared to second-generation beta blockers like atenolol. This study was planned
      to study the comparative effects of nebivolol and atenolol on metabolic
      parameters in patients with essential hypertension. MATERIALS AND METHODS: A
      prospective, randomized, parallel, open-label clinical study was carried out on
      patients with essential hypertension. The patients were randomly assigned to
      receive tablet atenolol (Group A) and nebivolol (Group B) for a period of 24
      weeks. Investigations were carried out at baseline and at the end of study
      period, that is, 24 weeks. Out of 69 patients, 60 completed the study and the
      data was analyzed using student's t-test. P < 0.05 was considered statistically
      significant. RESULTS: Atenolol and nebivolol both showed significant (P < 0.001)
      antihypertensive action after 24 weeks. Mean blood sugar and lipid profile were
      found to be significantly (P < 0.001) elevated after 24 weeks of treatment with
      atenolol but not with nebivolol. Heart rate was significantly (P < 0.001)
      decreased in both groups at 24 weeks. CONCLUSION: In view of metabolic adverse
      effects of atenolol, nebivolol is the better choice whenever beta-blockers have
      to be used in essential hypertension.

PMID- 21845002
TI  - The protective effect of Rubia cordifolia against lead nitrate-induced immune
      response impairment and kidney oxidative damage.
AB  - OBJECTIVES: To evaluate the in vivo antioxidant activity of the ethanolic extract
      of the roots of Rubia cordifolia (RC) and to study its influence on lead nitrate
      induced impairment of immune responses. MATERIALS AND METHODS: Seventy-two adult
      male Swiss albino mice were used for biochemical and immunological studies and
      were divided into six groups of six mice each. Mice were treated with lead
      nitrate (40 mg/kg, orally) either alone and or in combination with RC (50 and 100
      mg/kg body weight) daily for 40 days. For immunological studies, all mice were
      challenged twice with sheep RBC with on days 14 and 20 of the experiment. The
      immune function was assessed using macrophage yield, viability of macrophage,
      phagocytic index, serum immunoglobulin level, and plaque forming cell count
      (PFC), whereas the oxidative stress was assessed by estimating lipid peroxidation
      (LPO), reduced glutathione (GSH) content, and the activities of superoxide
      dismutase (SOD) and catalase (CAT). RESULTS: Lead nitrate administration induced
      a significant (P<0.001) increase in LPO, whereas a significant (P<0.001)
      depletion of CAT and GSH in renal tissues. In addition, it also showed a
      significant (P<0.001) reduction in macrophage yield, viability of macrophage,
      phagocyte index, serum immunoglobulin level, and PFC in kidney. However,
      combination treatment with RC observed a significant (P<0.001) reversal of lead
      nitrate-induced toxicity on oxidative stress and immunological parameters.
      CONCLUSION: The lead nitrate-induced immunosuppression is due to oxidative stress
      and RC can prevent the same by virtue of its in vivo antioxidant property.

PMID- 21845003
TI  - Effect of Montelukast on bradykinin-induced contraction of isolated tracheal
      smooth muscle of guinea pig.
AB  - AIM: To explore the effect of montelukast on bradykinin-induced tracheal smooth
      muscle contraction of isolated guinea pig trachea. STUDY DESIGN: To study the
      effect of bradykinin in the absence and in the presence of montelukast on the
      isolated tracheal smooth muscle of a guinea pig pretreated with indomethacin (10(
      6)M), phentolamine (10(-5)M), and propranalol (10(-6)M), to eliminate the effect
      of endogenous prostaglandins and catecholamines. The trachealis smooth muscle
      activity was recorded through the Isometric Force Displacement Transducer on a
      Four Channel Oscillograph. A cumulative dose-response relationship was
      demonstrated by adding successive doses of bradykinin on the tracheal strips,
      starting with 11 MUg to 77 MUg of 10(-4) concentration. A similar procedure was
      repeated in the presence of montelukast 0.5 MUg/ml, which, was equal to
      approximate C(max) achieved in vivo with a 10 mg oral dose of montelukast, and in
      the presence of 1 MUg/ml of montelukast. STATISTICAL ANALYSIS: Data was expressed
      as mean +/- standard error (SEM), and was analyzed using the SPSS version 15. A P
      value of less than 0.05 was considered significant. RESULTS: Bradykinin produced
      a dose-dependent, reversible contraction of isolated tracheal smooth muscle.
      Montelukast significantly reduced the bradykinin-induced tracheal smooth muscle
      reactivity and shifted the bradykinin curve to the right and downwards, in the
      presence of both concentrations of montelukast. The mean magnitude of response
      achieved with 77 MUg of bradykinin in the absence of montelukast was 39 mm +/-
      6.26, in the presence of 0.5 MUg/ml of montelukast it was 24.17 mm +/- 4.11, and
      in the presence of 1 MUg/ml of montelukast it was 13 mm +/- 2.6. CONCLUSION: It
      is concluded that montelukast significantly inhibits, in a dose-dependent manner,
      the bradykinin-induced contraction of the guinea pig tracheal smooth muscle, and
      alludes to an interaction between the bradykinin and leukotriene mediators.

PMID- 21845004
TI  - Antihyperglycemic and hypolipidemic activity of methanolic extract of Amaranthus
      viridis leaves in experimental diabetes.
AB  - To investigate the antihyperglycemic and hypolipidemic effects of methanolic
      extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ)
      induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of
      methanolic extract of leaves of Amaranthus viridis was evaluated by using normal
      and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day
      for 21 days. Blood glucose levels and body weight was monitored at specific
      intervals, and different biochemical parameters, serum cholesterol, serum
      triglyceride, high density lipoprotein, low density lipoprotein, very low density
      lipoprotein were also assessed in the experimental animals. Histology of pancreas
      was performed. The statistical data indicated a significant increase in the body
      weight, decrease in the blood glucose, total cholesterol and serum triglycerides
      after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was
      significantly increased when treated with extract. Histologically, focal necrosis
      was observed in the diabetic rat pancreas; however, was less obvious in treated
      groups. The MEAV has beneficial effects in reducing the elevated blood glucose
      level and body weight changes, and improves the lipid profile of STZ induced
      rats.

PMID- 21845005
TI  - Antidiabetic activity of ethanolic extract of tubers of Dioscorea alata in
      alloxan induced diabetic rats.
AB  - OBJECTIVE: To evaluate the antidiabetic activity of ethanolic extract of
      Dioscorea alata in glucose loaded and alloxan induced diabetic rats. MATERIALS
      AND METHODS: The authenticated tubers of D. alata (DA) (JSSCPDP/2008/157) were
      collected from Dharmapuri, Tamil Nadu. The ethanol extract was tested for
      hypoglycemic activity in normal rats. In oral glucose tolerance test, glucose (3
      g/kg, p.o.) was administered to non diabetic control, metformin (250 mg/kg, p.o.)
      and DA extract (100 and 200 mg/kg, p.o.) to treat treated rats. Diabetes mellitus
      was induced by alloxan monohydrate (120 mg/kg, i.p.) in physiological saline
      after overnight fasting for 18 hours. DA extract (100 and 200 mg/kg, p.o.) and
      standard drug metformin (250 mg/kg, p.o.) were administered to diabetic rats for
      21 days. Fasting blood glucose level and changes in body weight were measured on
      days 0, 7, 14, and 21. At the end of 21(st) day, serum lipid profile, total
      protein, albumin, and creatinine were assessed. RESULTS: In glucose loaded normal
      rats, the treatment with the extract of DA had shown a highly significant
      reduction (P < 0.001) in blood glucose levels at the doses of 100 and 200 mg/kg,
      respectively. The extract did not produce hypoglycemic activity at both the dose
      levels in normal, fasted rats. In alloxan induced diabetic rats, the body weight
      of the DA extract treated animals had shown a significant increase (P < 0.001)
      after 21 days treatment. The blood glucose level was reduced significantly by
      47.48% and 52.09% after 21 days treatment at dose levels 100 and 200 mg/kg,
      respectively. Serum lipid levels, total protein, albumin, and creatinine were
      reversed toward near normal in treated rats as compared to diabetic control.
      CONCLUSION: The results indicate that ethanol extract of DA tubers possesses
      significant antidiabetic activity.

PMID- 21845006
TI  - Delayed-onset akathisia due to amisulpride.
AB  - Despite the fact that second-generation antipsychotics have a lower potential to
      cause extrapyramidal side-effects, including akathisia, their incidence is not
      negligible. Recent work suggests that tardive akathisia may have pharmacological
      differences from acute akathisia. In the present study, we have evaluated the
      nature of delayed-onset akathisia in patients on amisulpride monotherapy.
      Overall, we screened 56 patients on amisulpride treatment for 2 months at a
      stabilized amisulpride dose. However, 18 patients with diagnostic and statistical
      manual of mental disorders-IV (DSM-IV) presented with acute or delayed-onset
      akathisia, and all of them also met the entry criteria. The patients were
      evaluated at baseline and at the time when akathisia presented clinically, with
      respect to the Positive and Negative Syndrome Scale and Barnes Akathisia Scale
      (BAS). Using the primary categorical criterion of akathisia (>=2 points of the
      BAS global scale), 12 (21.4%) of the 56 patients experienced delayed-onset
      akathisia, and six (10.7%) showed acute akathisia. The mean time for onset of
      acute or delayed-onset akathisia was 5.8 +/- 2.1 and 39.4 +/- 11.3 days,
      respectively. The mean BAS scores at baseline and after the period of 2 months
      were 1.3 +/- 0.6 and 3.9 +/- 2.4, respectively (P < 0.001). Our results revealed
      that amisulpride could considerably lead to delayed-onset akathisia. However,
      studies comprising larger samples receiving different antipsychotics, and more
      comprehensive assessment, will help to ascertain the role of amisulpride in
      delayed-onset akathisia.

PMID- 21845007
TI  - A comparative study of efficacy and safety of arformoterol and salbutamol
      nebulization as rescue therapy in acute non-severe asthma.
AB  - Arformoterol, a long-acting beta-2 agonist, has a rapid onset and long duration
      of action. Its role as rescue medication in acute asthma attack is undetermined.
      To compare the efficacy and tolerability of arformoterol with salbutamol
      nebulization, a study was conducted among 50 patients with acute non-severe
      asthma. Patients were randomly assigned to group 1 (n = 25) and group 2 (n = 25)
      who received three doses of salbutamol and arformoterol nebulization,
      respectively, at 20-min intervals. The peak expiratory flow rate (PEFR) was
      measured at the baseline and 5 min after each dose. The demographics and baseline
      characteristics were comparable between the two groups. The mean PEFR
      significantly increased in both these groups when compared with the baseline. The
      increases in the PEFR in two groups were similar after the third dose. The
      adverse effects in both these groups were minor. Arformoterol was as effective
      and safe as salbutamol in acute non-severe asthma.

PMID- 21845008
TI  - Effect of Unex on ethylene glycol-induced urolithiasis in rats.
AB  - This study was aimed to evaluate the effectiveness of the Unex capsule on albino
      rats as a preventive agent against the development of kidney stones. The Unex
      capsule is a marketed product of Unijules Life Sciences, Nagpur, containing the
      extracts of Boerhaavia diffusa and Tribulus terrestris. Activity of Unex was
      studied using the ethylene glycol-induced urolithiasis model. Standard drug used
      was Cystone. Several parameters were used including urinary volume, urine pH,
      urine analysis, and serum analysis to assess the activity. The results indicated
      that the administration of Unex to rats with ethylene glycol-induced lithiasis
      significantly reduced and prevented the growth of urinary stones (P < 0.01).
      Also, the treatment of lithiasis-induced rats by Unex restored all the elevated
      biochemical parameters (creatinine, uric acid, and blood urea nitrogen), restored
      the urine pH to normal, and increased the urine volume significantly (P < 0.01)
      when compared to the model control drug. This study supports the usage of Unex in
      urolithiasis and the utility could further be confirmed in other animal models.

PMID- 21845010
TI  - Sodium artesunate-induced diuresis in a patient with malaria.
AB  - Sodium artesunate is used in the treatment of malaria. We report a case of sodium
      artesunate induced diuresis and natriuresis in a patient with malaria. Following
      artesunate administration there was polyuria accompanied by natriuresis that was
      reversed after discontinuation of artesunate treatment. The diuretic effect of
      artesunate can modify the course of renal failure in severe malaria. Prescribers
      should be aware of this effect of artesunate, so that it can be used judiciously
      and to the advantage of patients with severe malaria.

PMID- 21845009
TI  - High anion gap refractory metabolic acidosis as a critical presentation of
      endosulfan poisoning.
AB  - Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such
      insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6
      methano-2,4,3-hexadithioxanthiep in 3-oxide) and it has been widely used in
      agriculture since 1960. The uncontrolled use of these compounds in developing
      countries has resulted in the deaths of animals and humans. Characteristic
      clinical signs following acute exposure are indicative of CNS disturbances or
      overstimulation. Mortality and morbidity rates are high and there is no specific
      antidote. We present an uncommon presentation of endosulfan poisoning in a 32
      year-old male with high anion gap severe refractory metabolic acidosis. The
      patient was treated with continuous renal replacement therapy and was salvaged.
      Till date, there is no case report from India for endosulfan poisoning with
      severe metabolic acidosis and hypotension. Through this case report, we emphasize
      the role of continuous renal replacement therapy as a rescue therapy for
      endosulfan poisoning with severe refractory metabolic acidosis and hypotension,
      even though it is a non dialyzable poison.

PMID- 21845011
TI  - Cholestatic hepatitis with intravenous ceftriaxone.
AB  - Drug-induced liver injury is a major health problem. Its predominant forms
      include acute hepatitis, cholestasis, and a mixed pattern. Ceftriaxone is a third
      generation cephalosporin and is widely used in the postoperative period due to
      its wider spectrum, longer half-life, and better tissue penetrability. Earlier
      cases of high aminotransferase levels and hepatitis have also been reported with
      the use of ceftriaxone. Here we report a case of cholestatic hepatitis with
      intravenous ceftriaxone.

PMID- 21845012
TI  - Propofol-induced violent coughing in a patient with Becker's muscular dystrophy.
AB  - Propofol anesthesia is often associated with decreased incidence of gagging,
      coughing or laryngospasm, and provides intense suppression on airway reflex
      during tracheal intubation and laryngeal mask airway insertion. Propofol
      pretreatment is also effective in reducing the occurrence of opioid-induced
      coughing. These benefits are often attributed to bronchodilator and sedative
      effects of propofol. However, severe coughing following sedative doses of 1%
      propofol has not been reported so far. We report a rare case of violent coughing
      following low-dose propofol infusion in a patient with Becker's muscular
      dystrophy.

PMID- 21845014
TI  - Perspectives regarding intended learning outcomes in pharmacology.

PMID- 21845013
TI  - Deep vein and artery thrombosis associated with cetuximab-based
      chemoradiotherapy.
AB  - Molecular targeted agents have lower hematological toxicity. However, specific
      side-effects such as allergic rashes, skin reactions and high cost limit their
      use. We report a case of 35-year-old male patient with carcinoma of left tonsil
      treated with concurrent cetuximab and radiotherapy. After four weeks of
      treatment, the patient developed sudden onset of pain in the left calf region
      radiating to the left foot. Doppler study of the left lower limb revealed
      complete thrombosis of superficial femoral, popliteal and proximal tibial
      arteries and veins and no flow in anterior tibial artery and lower posterior
      tibial artery. Emergency embolectomy was done. After 48 h of observation, no
      improvement was noted. A repeat Doppler examination showed similar finding.
      Ultimately a left lower limb amputation was done. We report simultaneous arterio
      venous thrombosis associated with cetuximab-based chemoradiotherapy. Oncologists
      should be aware of this possible complication to undertake early intervention.

PMID- 21845015
TI  - A case of look-alike medication errors.

PMID- 21845016
TI  - Direct to consumer advertising of prescription drugs on internet: A Boon or a
      Curse.

PMID- 21845017
TI  - Vaccines for type 1 diabetes in the late stage of clinical development.

PMID- 21845018
TI  - Authors' reply.

PMID- 21845019
TI  - Experimental evaluation of antipyretic and analgesic activities of aspartame.

PMID- 21845020
TI  - Optimization process planning using hybrid genetic algorithm and intelligent
      search for job shop machining.
AB  - Optimization of process planning is considered as the key technology for computer
      aided process planning which is a rather complex and difficult procedure. A good
      process plan of a part is built up based on two elements: (1) the optimized
      sequence of the operations of the part; and (2) the optimized selection of the
      machine, cutting tool and Tool Access Direction (TAD) for each operation. In the
      present work, the process planning is divided into preliminary planning, and
      secondary/detailed planning. In the preliminary stage, based on the analysis of
      order and clustering constraints as a compulsive constraint aggregation in
      operation sequencing and using an intelligent searching strategy, the feasible
      sequences are generated. Then, in the detailed planning stage, using the genetic
      algorithm which prunes the initial feasible sequences, the optimized operation
      sequence and the optimized selection of the machine, cutting tool and TAD for
      each operation based on optimization constraints as an additive constraint
      aggregation are obtained. The main contribution of this work is the optimization
      of sequence of the operations of the part, and optimization of machine selection,
      cutting tool and TAD for each operation using the intelligent search and genetic
      algorithm simultaneously.

PMID- 21845021
TI  - Relations between Executive Function and Academic Achievement from Ages 5 to 17
      in a Large, Representative National Sample.
AB  - This study examined age-related changes in complex executive function (EF) in a
      large, representative sample (N = 2,036) aged 5 to 17 using the Cognitive
      Assessment System (CAS; Naglieri & Das, 1997a). Relations between complex EF and
      academic achievement were examined on a sub-sample (N = 1,395) given the Woodcock
      Johnson Tests of Achievement-Revised (Woodcock & Johnson, 1989). Performance on
      the three complex EF tasks improved until at least age 15, although improvement
      slowed with increasing age and varied some across tasks. Moreover, the different
      developmental patterns in the correlations between completion time and accuracy
      provide clues to developmental processes. Examination of individual achievement
      subtests clarified the specific aspects of academic performance most related to
      complex EF. Finally, the correlation between complex EF and academic achievement
      varied across ages, but the developmental pattern of the strength of these
      correlations was remarkably similar for overall math and reading achievement,
      suggesting a domain-general relation between complex EF and academic achievement.

PMID- 21845023
TI  - SILS Incisional Hernia Repair: Is It Feasible in Giant Hernias? A Report of Three
      Cases.
AB  - Aim. Three incisional ventral abdominal wall hernias were repaired by placing a
      20 * 30 cm composite mesh via single incision of 2 cm. Methods. All three cases
      had previous operations and presented with giant incisional defects clinically.
      The defects were repaired laparoscopically via single incision with the placement
      of a composite mesh of 20 * 30 cm. Nonabsorbable sutures were needed to hang and
      fix the mesh only in the first case. Double-crown technique was used in all of
      the cases to secure the mesh to the anterior abdominal wall. Results. The mean
      operation time was 120 minutes. The patients were mobilized and led for oral
      intake at the first postoperative day. No morbidity occurred. Conclusion.
      Abdominal incisional hernias can be repaired via single incision with a mesh
      application in experienced centers.

PMID- 21845022
TI  - Do women using long-acting reversible contraception reduce condom use? A novel
      study design incorporating semen biomarkers.
AB  - Long-acting reversible contraceptive (LARC) methods are highly effective against
      pregnancy. A barrier to their widespread promotion can include the concern they
      will lead reduced condom use and, thus, will put couples at higher risk for
      sexually transmitted infections (STIs). We review evidence from previous studies
      of condom "migration" associated with the use of LARC and propose a novel study
      design to address the two main methodological issues that have limited these
      earlier studies. Namely, we propose to use a randomized controlled trial design
      and to use a biological marker of semen exposure for measuring changes in condom
      use.

PMID- 21845024
TI  - Histone deacetylases in neural stem cells and induced pluripotent stem cells.
AB  - Stem cells have provided great hope for the treatment of a variety of human
      diseases. However, the molecular mechanisms underlying stem cell pluripotency,
      self-renewal, and differentiation remain to be unveiled. Epigenetic regulators,
      including histone deacetylases (HDACs), have been shown to coordinate with cell
      intrinsic transcription factors and various signaling pathways to regulate stem
      cell pluripotency, self-renewal, and fate determination. This paper focuses on
      the role of HDACs in the proliferation and neuronal differentiation of neural
      stem cells and the application of HDAC inhibitors in reprogramming somatic cells
      to induced pluripotent stem cells (iPSCs). It promises to be an active area of
      future research.

PMID- 21845025
TI  - New retinal imaging for the visualization and analysis of vitreoretinal interface
      (VRI) by short-wavelength scanning laser ophthalmoscope (swSLO).
AB  - BACKGROUND: The purpose of the study was to evaluate vitreoretinal interface
      (VRI) alteration with a short-wavelength scanning laser ophthalmoscope (swSLO),
      the Nidek F-10, and compare the results with those obtained by means of spectral
      domain optical coherence tomography (SD-OCT). METHODS: Thirty-six eyes were
      studied (20 patients, mean age 68 +/- 12.3 years). All patients underwent a
      complete ophthalmologic examination, which comprised SD-OCT and Nidek F-10
      analysis with short-wavelength blue laser. Eyes were divided into four groups
      depending on the degree of VRI alteration observed with the swSLO and SD-OCT.
      Statistical analysis was performed using the Chi-square test. P values less than
      0.05 were considered statistically significant. RESULTS: OCT ANALYSIS: eight eyes
      (22%) grade 0 (no abnormalities), 15 eyes (42%) grade 1 (preretinal cellophane);
      seven (19%) grade 2 (preretinal wrinkling); six (17%) grade 3 (macular pucker or
      hole). Nidek F-10 analysis: seven (19%) grade 0, 16 (45%) grade 1; seven (19%)
      grade 2; six (17%) grade 3. Chi-square = 0.099, P = 0.992. There was no
      statistically significant difference between the two instruments. CONCLUSION:
      Nidek F-10 allows both a quantitative and a qualitative evaluation of VRI and is
      equal to SD-OCT in detecting alteration of the inner portion of the retina,
      providing an easy way to evaluate and map differences in the inner vitreoretinal
      surface.

PMID- 21845026
TI  - Intravitreal bevacizumab alone or combined with triamcinolone acetonide as the
      primary treatment for diabetic macular edema.
AB  - PURPOSE: To compare the efficacy of intravitreal injection of bevacizumab alone
      or combined with intravitreal triamcinolone as the primary treatment for cases
      with diabetic macular edema (DME). METHODS: Ninety eyes were enrolled in one of
      the three study arms; where intravitreal triamcinolone acetonide (IVT) was used
      in group I, IVT/intravitreal bevacizumab (IVT/IVB) in group II, and IVB in group
      III. The visual acuity (VA) and central macular thickness (CMT) were used as the
      outcome measures, where the results of each group were calculated and compared
      with the results of the other. RESULTS: There was significant improvement in the
      VA in the three study groups at weeks 6 and 12; with regards to the intraocular
      pressure (IOP), there was significant difference at week 6 in the IVT and IVT/IVB
      groups, and at week 12 in IVT/IVB group, and nonsignificant difference at week 6
      in the IVB group and at week 12 in IVT and IVB groups. CONCLUSION: From this
      study, we conclude that IVB is an effective drug for treatment of DME, and has a
      long lasting effect when compared with IVT and when compared with combined
      IVT/IVB; adding IVT does not affect the outcome measures except for elevating the
      IOP in treated patients in the early post-injection period.

PMID- 21845027
TI  - Femtosecond-assisted preparation of donor tissue for Boston type 1
      keratoprosthesis.
AB  - We describe a technique for femtosecond laser-assisted preparation of donor
      tissue for Boston type 1 keratoprosthesis to provide accurate double punching of
      the donor tissue for optimized alignment in the visual axis. The technique was
      reproducibly performed in four donor corneas mounted in an artificial anterior
      chamber. This technique can provide optically centered donor tissue with smooth
      trephinated edges.

PMID- 21845028
TI  - Predictive value of visual evoked potentials, relative afferent pupillary defect,
      and orbital fractures in patients with traumatic optic neuropathy.
AB  - BACKGROUND: The purpose of this study was to determine the predictive value of
      flash visual-evoked potentials (VEP), relative afferent pupillary defect, and
      presence of orbital fractures in patients with traumatic optic neuropathy.
      METHODS: A prospective study was conducted in 15 patients with indirect traumatic
      optic neuropathy. All patients underwent a thorough ophthalmic examination.
      Initial visual acuity, final visual acuity, and relative afferent pupillary
      defect were determined, and visual acuity was converted into logMAR units. We
      performed flash VEP and an orbital computed tomography scan in all patients.
      RESULTS: There was a good correlation between relative afferent pupillary defect
      and final visual acuity (r = -0.83), and better initial visual acuity could
      predict better final visual acuity (r = 0.92). According to findings from flash
      VEP parameters, there was a relationship between final visual acuity and
      amplitude ratio of the wave (r = 0.59) and latency ratio of the wave (r = -0.61).
      Neither primary visual acuity nor final visual acuity was related to the presence
      of orbital fractures in the orbital CT scan. CONCLUSION: Patients with traumatic
      optic neuropathy often present with severe vision loss. Flash VEP, poor initial
      visual acuity, and higher grade of relative afferent pupillary defect could
      predict final visual acuity in these patients. Presence of orbital fracture was
      not a predictive factor for primary visual acuity or final visual acuity.

PMID- 21845029
TI  - Unexplained postoperative retinal hemorrhage after 23-gauge sutureless
      vitrectomy.
AB  - We report five cases of unexplained retinal hemorrhage after 23-gauge sutureless
      vitrectomy. A 23-gauge sutureless vitrectomy was performed for four cases of
      macular holes (MH) and one case of macular hole retinal detachment (MHRD).
      Retinal hemorrhages were observed on the first day after surgery and disappeared
      within several months without leaving any recognizable damage. We speculate that
      the retinal hemorrhages might have resulted from repeated collapse of the globe
      through a cannula under air perfusion, but other causes such as retinal vein
      congestion by face-down positioning are also possible.

PMID- 21845030
TI  - Grid photocoagulation combined with intravitreal bevacizumab for recurrent
      macular edema associated with retinal vein occlusion.
AB  - PURPOSE: To report the efficacy of grid photocoagulation combined with
      intravitreal bevacizumab (IVB) for macular edema recurring after previous IVBs
      associated with retinal vein occlusion (RVO). METHODS: This retrospective study
      consisted of 19 eyes with branch retinal vein occlusion (BRVO) and nine eyes with
      central retinal vein occlusion (CRVO), which were treated with grid
      photocoagulation combined with IVB for recurrent macular edema after previous
      IVBs. The mean duration of total follow-up was 29.3 +/- 5.8 months. RESULTS:
      After this combination therapy, foveal thickness was reduced, significant with
      slight improvement in visual acuity (VA). At 1 month after treatment, although 25
      of the 28 eyes showed complete resolution of the cystoid space, the macular edema
      recurred to some extent in 19 eyes. Compared with initial values, final foveal
      thickness was reduced significantly in both BRVO and CRVO groups (P < 0.001), but
      improvement in VA was significant only for eyes with BRVO (P = 0.012). The total
      number of IVB was 2.8 +/- 0.7 for eyes with either BRVO or CRVO. CONCLUSION: Grid
      photocoagulation combined with IVB has a substantial effect on reducing recurrent
      macular edema associated with RVO, but the effect on visual acuity is limited.

PMID- 21845031
TI  - Changes in corneal parameters at confocal microscopy in treated glaucoma
      patients.
AB  - BACKGROUND: The purpose of this study was to evaluate corneal parameters in
      treated glaucoma patients, nontreated glaucoma patients, and normal subjects
      using confocal microscopy. METHODS: Forty patients with primary open-angle
      glaucoma and 22 untreated controls underwent confocal microscopy of the cornea
      using the Heidelberg retinal tomograph cornea module. The glaucoma group was
      divided into two subgroups, ie, patients on medical treatment for at least two
      years before inclusion (with beta-blockers or prostaglandin analogs) and
      nontreated glaucoma patients. The following corneal parameters were evaluated:
      endothelial cell density and number, reflectivity, and tortuosity of sub-basal
      nerves. For reflectivity and tortuosity, a dedicated grading scale ranging from 0
      to 4 was used. Differences between treatments were also evaluated in the treated
      glaucoma group. RESULTS: Number of fibers and reflectivity of the sub-basal
      plexus were significantly lower in glaucoma patients as compared with controls
      (2.5 +/- 0.7 versus 2.9 +/- 0.9, P = 0.006, and 2.3 +/- 0.8 versus 2.7 +/- 0.9, P
      = 0.04, respectively), whereas tortuosity was significantly higher (2.6 +/- 1
      versus 2.0 +/- 0.8, P = 0.007). Endothelial cell density (measured as cells per
      mm(2)) was lower in the glaucoma group comparing treated patients with nontreated
      patients (2826 +/- 285 versus 3124 +/- 272, P = 0.0003). Comparing treated
      patients with nontreated patients, relevant differences were found in number (2.3
      +/- 0.7 versus 2.8 +/- 0.8, P = 0.004), tortuosity (2.8 +/- 1 versus 2.2 +/- 0.8,
      P = 0.004), and reflectivity (2.2 +/- 0.8 versus 2.6 +/- 0.8, P = 0.04). No
      differences in corneal parameters were found between beta-blockers and
      prostaglandin analogs. CONCLUSION: This study shows that differences in corneal
      parameters between glaucoma patients and controls may be due to the medical
      treatments used for glaucoma. These data should be taken into consideration in
      long-standing medical glaucoma treatment and in potential candidates for surgery.

PMID- 21845032
TI  - Critical appraisal of the clinical utility of the dexamethasone intravitreal
      implant (Ozurdex) for the treatment of macular edema related to branch retinal
      vein occlusion or central retinal vein occlusion.
AB  - Macular edema is a common cause of visual loss in patients with retinal vein
      occlusions. Ozurdex((r)), a dexamethasone intravitreal implant, has been shown in
      randomized controlled trials to reduce macular edema and improve visual acuity in
      patients with either branch retinal vein occlusions or central retinal vein
      occlusions. It was approved in the United States in 2009. Since then, new
      therapeutic agents and clinical data have emerged. The purpose of this review is
      to critically evaluate the clinical utility of Ozurdex((r)) in the current
      treatment strategy of macular edema related to retinal vein occlusion.

PMID- 21845033
TI  - Long-term success of intravitreal bevacizumab for choroidal neovascularization
      associated with choroidal osteoma.
AB  - PURPOSE: To describe a case of choroidal osteoma with choroidal
      neovascularization (CNV) that was successfully treated with two intravitreal
      injections of bevacizumab (IVB). DESIGN AND METHODS: Case report on a 12-year-old
      Japanese girl who presented with a sudden decrease in vision in her left eye. At
      the first visit, 2 days after the onset of her symptoms, her visual acuity (VA)
      in her left eye was 0.2. Ophthalmoscopy showed a hemorrhage of 5 disc diameters
      under the retinal pigment epithelium and a serous retinal detachment at the
      posterior pole of the left eye. These findings were confirmed by optical
      coherence tomography. Fluorescein angiography (FA) and indocyanine green
      angiography (ICGA) showed several points of leakage around the fovea, which
      suggested a CNV. From these findings, the patient was diagnosed with choroidal
      osteoma with a CNV. The submacular hemorrhage was from the CNV associated with
      the choroidal osteoma. We treated her with two injections of 1.25 mg/0.05 mL IVB
      with a 4-month interval. RESULTS: The patient's VA in her left eye improved to
      0.7, and this vision was maintained for 4 years. The CNV disappeared in the FA
      and ICGA images and no recurrence was observed after 4 years. CONCLUSION: Our
      findings indicate that IVB is effective in resolving CNV in eyes with an osteoma
      and prevents a decrease of vision in eyes with a choroidal osteoma with a CNV.

PMID- 21845034
TI  - Duloxetine in the management of diabetic peripheral neuropathic pain.
AB  - Diabetic neuropathy affects up to 70% of diabetics, and diabetic peripheral
      neuropathic pain (DPNP) is the most common and debilitating of the diabetic
      neuropathies. DPNP significantly reduces quality of life and increases management
      costs in affected patients. Despite the impact of DPNP, management is poor with
      one-quarter of patients receiving no treatment and many treated with medications
      having little or no efficacy in managing DPNP. Duloxetine is one of two drugs
      approved by the United States Food and Drug Administration for DPNP management.
      Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) proven
      safe, effective, and cost-saving in reducing DPNP symptoms at a dose of 60
      mg/day. Duloxetine doses greater than 60 mg/day for DPNP management are not
      recommended since they are no more efficacious and associated with more side
      effects; addition of pregabalin or gabapentin for these patients may be
      beneficial. Side effects of duloxetine are generally mild and typical for the
      SNRI class including nausea, dizziness, somnolence, fatigue, sweating, dry mouth,
      constipation, and diarrhea. Given its other indications, duloxetine is a
      particularly good choice for DPNP treatment in patients with coexisting
      depression, anxiety, fibromyalgia, or chronic musculoskeletal pain. Duloxetine
      treatment had no clinically significant effect on glycemic control and did not
      increase the risk of cardiovascular events in diabetes patients. However,
      duloxetine use should be avoided in patients with hepatic disease or severe renal
      impairment. Given its safety, efficacy, and tolerability, duloxetine is an
      excellent choice for DPNP treatment in many patients.

PMID- 21845035
TI  - Treatment simplification in HIV-infected adults as a strategy to prevent
      toxicity, improve adherence, quality of life and decrease healthcare costs.
AB  - Since the advent of highly active antiretroviral therapy (HAART), the treatment
      of human immunodeficiency virus (HIV) infection has become more potent and better
      tolerated. While the current treatment regimens still have limitations, they are
      more effective, more convenient, and less toxic than regimens used in the early
      HAART era, and new agents, formulations and strategies continue to be developed.
      Simplification of therapy is an option for many patients currently being treated
      with antiretroviral therapy (ART). The main goals are to reduce pill burden,
      improve quality of life and enhance medication adherence, while minimizing short-
      and long-term toxicities, reducing the risk of virologic failure and maximizing
      cost-effectiveness. ART simplification strategies that are currently used or are
      under study include the use of once-daily regimens, less toxic drugs, fixed-dose
      coformulations and induction-maintenance approaches. Improved adherence and
      persistence have been observed with the adoption of some of these strategies. The
      role of regimen simplification has implications not only for individual patients,
      but also for health care policy. With increased interest in ART regimen
      simplification, it is critical to study not only implications for individual
      tolerability, toxicity, adherence, persistence and virologic efficacy, but also
      cost, scalability, and potential for dissemination and implementation, such that
      limited human and financial resources are optimally allocated for maximal
      efficiency, coverage and sustainability of global HIV/AIDS treatment.

PMID- 21845036
TI  - Management of oropharyngeal candidiasis with localized oral miconazole therapy:
      efficacy, safety, and patient acceptability.
AB  - Oropharyngeal candidiasis is a very common localized infection of the mucus
      membranes of the oropharynx that is most commonly caused by the patient's own
      commensal Candida albicans. It is the most common opportunistic infection
      affecting patients with the human immunodeficiency virus (HIV) and is also quite
      common in patients with hematological malignancies. Effective treatment options
      are of high importance given the worldwide incidence of these disease states and
      the potential for development of oropharyngeal candidiasis in these patients.
      Various systemic and topical treatment options for patients with oropharyngeal
      candidiasis have existed for many years. Miconazole buccal tablets have recently
      been approved by the US Food and Drug Administration for the treatment of
      oropharyngeal candidiasis. Clinical trials have demonstrated noninferiority in
      the treatment of oropharyngeal candidiasis when compared with clotrimazole
      troches in patients with HIV and against miconazole gel in patients with head and
      neck cancer. Miconazole buccal tablets exhibit few drug interactions because of
      low systemic absorption and are generally well tolerated with a safety profile
      similar to comparators. The once-daily dosing schedule may improve patient
      adherence compared with topical alternatives; however, the cost of therapy may be
      a barrier for some patients and should be considered by prescribers compared with
      alternative treatments.

PMID- 21845037
TI  - Outcomes associated with initiation of tiotropium or fluticasone/salmeterol in
      patients with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Adherence to long-acting bronchodilator therapy for management of
      chronic obstructive pulmonary disease (COPD) is a critical clinical and cost
      issue. Low adherence is associated with relatively higher exacerbation rates and
      illness burden. PURPOSE: To compare adherence between patients with COPD
      initiating therapy on tiotropium or fluticasone/salmeterol and examine the
      association between adherence and respiratory-related costs. PATIENTS AND
      METHODS: This retrospective claims data analysis evaluated patients initiating
      tiotropium or combination fluticasone/salmeterol from December 1, 2004 to
      December 31, 2005. Patients had >=1 COPD diagnosis (International Classification
      of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 491.xx, 492.x, 496)
      and were observed during 6-month pre-index and variable (12-18-month) post-index
      periods. Outcomes were adherence to and discontinuation of therapy, and
      respiratory-related inpatient, medical, and total health care costs. Adherence
      was medication possession ratio >=0.80. Discontinuation, adherence, and costs
      were analyzed with Cox proportional hazards regression, logistic regression, and
      generalized linear model regressions, respectively. Regressions controlled for
      demographic, sociodemographic, and health status factors. RESULTS: The study
      population comprised 1561 tiotropium and 2976 fluticasone/salmeterol patients. In
      unadjusted comparisons: 19.5% and 8.5% of tiotropium and fluticasone/salmeterol
      patients, respectively, were adherent (P < 0.001); tiotropium patients versus
      fluticasone/salmeterol patients had higher mean respiratory-related pharmacy
      costs (US$1080 versus US$974, P = 0.002) and health care costs (US$3751 versus
      US$2932, P = 0.031). Regression analysis showed tiotropium patients were 31.6%
      less likely to discontinue therapy (95% confidence interval [CI]: 0.64-0.73) and
      had 2.25 times higher odds of adherence (CI: 1.85-2.73) versus
      fluticasone/salmeterol patients. The associations between index therapy and costs
      were not significant. Adherence versus nonadherence was associated with: 46.9%
      higher health care costs (CI: 1.13-1.91); 37.1% lower medical costs (CI: 0.43
      0.91); and 53.4% lower inpatient costs (CI: 0.30-0.72). CONCLUSION: Patients with
      COPD initiating long-acting bronchodilator therapy were more likely to be
      adherent to tiotropium than to fluticasone/salmeterol. Adherence to either
      tiotropium or to fluticasone/salmeterol was associated with lower respiratory
      related medical and inpatient costs, and with higher respiratory-related total
      health care costs.

PMID- 21845038
TI  - Tiotropium reduces risk of exacerbations irrespective of previous use of inhaled
      anticholinergics in placebo-controlled clinical trials.
AB  - BACKGROUND: Data have highlighted the potential bias introduced by withdrawal of
      inhaled corticosteroids at randomization in chronic obstructive pulmonary disease
      trials examining inhaled corticosteroids. Analyses were conducted to determine
      whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.
      METHODS: A pooled analysis of randomized, double-blind, placebo-controlled,
      parallel-group tiotropium trials of at least six months' duration was performed.
      Trials had similar inclusion and exclusion criteria. Exacerbation definition was
      standardized. Patients were divided into two groups, ie, D (anticholinergics
      discontinued at randomization, previously prescribed) and ND (anticholinergics
      not discontinued, not previously prescribed). RESULTS: Demographics were balanced
      between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative
      smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in
      one second (FEV(1))/forced vital capacity (43% versus 48%), and lower baseline
      FEV(1) (35.8% predicted versus 42.4% predicted) in the D group. In both groups,
      tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P <
      0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR =
      0.85, P = 0.0467 versus 0.79, P = 0.0094). Tiotropium reduced the number of
      exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR
      = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR =
      0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]). CONCLUSION: Tiotropium
      reduced exacerbations in patients who did and did not have anticholinergics
      discontinued upon randomization in clinical trials.

PMID- 21845039
TI  - Nickel nanowires induced and reactive oxygen species mediated apoptosis in human
      pancreatic adenocarcinoma cells.
AB  - BACKGROUND: The ability to evade apoptosis is one of the key properties of
      cancer. The apoptogenic effect of nickel nanowires (Ni NWs) on cancer cell lines
      has never been adequately addressed. Due to the unique physicochemical
      characteristics of Ni NWs, we envision the development of a novel anticancer
      therapeutics specifically for pancreatic cancer. Thus, we investigated whether Ni
      NWs induce ROS-mediated apoptosis in human pancreatic adenocarcinoma (Panc-1)
      cells. METHODS: In this study Ni NWs were fabricated using the electrodeposition
      method. Synthesized Ni NWs were physically characterized by energy dispersive X
      ray analysis, UV-Vis spectroscopy of NanoDrop 2000 (UV-Vis), magnetization study,
      scanning electron microscopy, and transmission electron microscopy. Assessment of
      morphological apoptotic characteristics by phase contrast microscopy (PCM), Ni
      NWs-induced apoptosis staining with ethidium bromide (EB) and acridine orange
      (AO) followed by fluorescence microscopy (FM) was performed. For molecular
      biological and biochemical characterization, Panc-1 cell culture and cytotoxic
      effect of Ni NWs were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyl tetrazolium bromide (MTT) assay. Quantitative apoptosis was analyzed by
      flow cytometry staining with propidium iodide through cell cycle arrest and
      generation of ROS using 2', 7'-dichlorofluorescein diacetate fluorescence
      intensity. In all experiments, Panc-1 cancer cells without any treatment were
      used as the negative controls. RESULTS: The intracellular uptake of Ni NWs
      through endocytosis by Panc-1 cells was observed by PCM. EB and AO staining of FM
      and MTT assay qualitatively and quantitatively confirmed the extent of apoptosis.
      Flow cytometric cell cycle arrest and ROS generation indicated Ni NWs as inducers
      of apoptotic cell death. CONCLUSION: We investigated the role of Ni NWs as
      inducers of ROS-mediated apoptosis in Panc-1 cells. These results suggested that
      Ni NWs could be an effective apoptotic agent for Panc-1 cells and have good
      potential for further research into a clinical treatment selective for pancreatic
      cancer.

PMID- 21845040
TI  - Poly (epsilon-caprolactone) nanofibrous ring surrounding a polyvinyl alcohol
      hydrogel for the development of a biocompatible two-part artificial cornea.
AB  - The study aimed to fabricate and characterize a 2-part artificial cornea as a
      substitute for penetrating keratoplasty in patients with corneal blindness. The
      peripheral part of the artificial cornea consisted of plasma-treated electrospun
      poly (E-caprolactone) (PCL) nanofibers, which were attached to a hydrogel disc of
      polyvinyl alcohol (PVA) as a central optical part. The physical properties of the
      prepared artificial cornea, including morphology, mechanical properties, light
      transmittance, and contact angle, were assessed. Cell attachment and
      proliferation studies were performed on rabbit limbal stem cells. The SEM image
      of the polymeric system showed that the peripheral part formed a highly porous
      scaffold that could facilitate tissue biointegration. Assessment of the
      mechanical properties of the peripheral nanofibrous part and the hydrogel optical
      part showed suitable elasticity. Young's modulus values of the electrospun PCL
      skirt and PVA hydrogel core were 7.5 and 5.3 MPa, respectively, which is in line
      with the elasticity range of natural human cornea (0.3-7 MPa). The light
      transmittance of the central part was >85% when measured in the 400-800 nm
      wavelength range. The plasma-treated PCL nanofibrous scaffold promoted limbal
      stem cell adhesion and proliferation within 10 days. These results confirmed that
      the polymeric artificial cornea showed suitable physical properties and good
      biocompatibility and epithelialization ability.

PMID- 21845041
TI  - Optimizing particle size for targeting diseased microvasculature: from
      experiments to artificial neural networks.
AB  - BACKGROUND: Nanoparticles with different sizes, shapes, and surface properties
      are being developed for the early diagnosis, imaging, and treatment of a range of
      diseases. Identifying the optimal configuration that maximizes nanoparticle
      accumulation at the diseased site is of vital importance. In this work, using a
      parallel plate flow chamber apparatus, it is demonstrated that an optimal
      particle diameter (d(opt)) exists for which the number (n(s)) of nanoparticles
      adhering to the vessel walls is maximized. Such a diameter depends on the wall
      shear rate (S). Artificial neural networks are proposed as a tool to predict n(s)
      as a function of S and particle diameter (d), from which to eventually derive
      d(opt). Artificial neural networks are trained using data from flow chamber
      experiments. Two networks are used, ie, ANN231 and ANN2321, exhibiting an
      accurate prediction for n(s) and its complex functional dependence on d and S.
      This demonstrates that artificial neural networks can be used effectively to
      minimize the number of experiments needed without compromising the accuracy of
      the study. A similar procedure could potentially be used equally effectively for
      in vivo analysis.

PMID- 21845042
TI  - New tumor-targeted nanosized delivery carrier for oligonucleotides:
      characteristics in vitro and in vivo.
AB  - BACKGROUND: The purpose of this study was to investigate the in vitro and in vivo
      characteristics of a new tumor-targeted nanosized delivery carrier for antisense
      oligonucleotide (ASON). METHODS: Polyethylenimine (PEI) was used to condense ASON
      to form nanosized complexes (PEI/ASON), which were then modified using asparagine
      glycine-arginine (NGR) peptide to obtain a tumor-targeted nanosized delivery
      carrier (NGR/PEI/ASON). The conditions required to form PEI/ASON were
      investigated. RESULTS: A linear correlation between the natural logarithm of the
      N/P ratio (PEI to ASON) and the zeta potential of the PEI/ASON complexes was
      found, ranging from 1.5 to 5.0. The pH of the solution strongly influenced the
      zeta potential of the PEI/ASON complexes. PEI/ASON and NGR/PEI/ASON were stable
      in RPMI-1640 culture medium in the presence of Dextran 70. Incorporation of ASON
      into PEI/ASON and NGR/PEI/ASON complexes prevented degradation of ASON by DNase
      I. CONCLUSION: Both ASON/PEI and NGR/PEI/ASON complexes enhanced the uptake of
      ASON by EC9706 cells in vitro. In vivo, NGR/PEI/ASON complexes had the ability to
      target tumor tissues effectively.

PMID- 21845043
TI  - Suitable carriers for encapsulation and distribution of endostar: comparison of
      endostar-loaded particulate carriers.
AB  - BACKGROUND: Particulate carriers are necessary to control the release of endostar
      and prolong its circulation in vivo. The purpose of this study was to identify a
      suitable carrier for the capsulation and delivery of endostar. METHODS: We
      prepared a series of poly (DL-lactide-co-glycolide) (PLGA) and poly (ethylene
      glycol) (PEG)-modified PLGA (PEG-PLGA) particulate carriers, and then
      characterized them according to their ability to prolong the circulation of
      endostar, their physicochemical properties, endostar-loading content, and in
      vitro and in vivo particulate carrier release profiles. RESULTS: All the
      particulate carriers had spherical core shell structures. The PEG-PLGA material
      and nanosize range appeared to enable the carriers to encapsulate more endostar,
      release endostar faster in vitro, and accumulate more endostar in vivo. The drug
      loading capacity of PEG-PLGA and PLGA nanoparticles was 8.03% +/- 3.41% and 3.27%
      +/- 5.26%, respectively, and for PEG-PLGA and PLGA microspheres was 15.32% +/-
      5.61% and 9.21% +/- 4.73%. The cumulative amount of endostar released from the
      carriers in phosphate-buffered saline over 21 days was 23.79%, 20.45%, 15.13%,
      and 10.41%, respectively. Moreover, the terminal elimination half-life of
      endostar in the rabbit was 26.91 +/- 7.93 hours and 9.32 +/- 5.53 hours in the
      PEG-PLGA group and the PLGA nanoparticle group. Peak endostar concentration was
      reached at day 7 in the group treated with subcutaneous injection of PEG-PLGA
      microspheres and at day 14 in the group receiving subcutaneous injection of PLGA
      microspheres. Endostar was detectable in vivo in both groups after injection of
      the particulate carriers. CONCLUSION: PEG-PLGA nanoparticles might be better than
      other nanoparticulate carriers for encapsulation and distribution of endostar.

PMID- 21845044
TI  - Evaluation of injectable silica-embedded nanohydroxyapatite bone substitute in a
      rat tibia defect model.
AB  - In clinical practice, vertebral compression fractures occur after trauma and
      osteoporosis. Kyphoplasty is a minimally invasive procedure using bone filler
      material for the treatment of such fractures. A full synthetic injectable bone
      substitute (SIBS) was manufactured by means of spray drying. The aim of this
      study was to characterize the SIBS and to analyze the remodelling process during
      degradation of the biomaterial and new bone formation after implantation. SIBS is
      an aqueous suspension of donut-like microparticles. These microparticles consist
      of nanocrystallites of synthetic hydroxyapatite embedded in amorphous silica gel.
      After implantation of SIBS in a proximal tibial diaphyseal defect in 52 rats,
      grafts were harvested for subsequent analysis on different days. Newly formed
      bone originating from endosteum was observed on day 6. Hematomas in the medullary
      space and cortical wounds disappeared on day 12. The wound region was completely
      replaced by a composite of newly formed cancellous bone, extracellular matrix,
      and SIBS. At day 63 the cortical defect was fully healed by bone, while newly
      formed bone in the medullary space almost disappeared and was replaced with bone
      marrow. In conclusion, SIBS demonstrated a unique structure with osteoinductive
      and bioresorbable properties, which induced fast bone regeneration. Therefore, a
      clinical application of SIBS for kyphoplasty is promising.

PMID- 21845045
TI  - Selenium nanoparticles inhibit Staphylococcus aureus growth.
AB  - Staphylococcus aureus is a key bacterium commonly found in numerous infections.
      S. aureus infections are difficult to treat due to their biofilm formation and
      documented antibiotic resistance. While selenium has been used for a wide range
      of applications including anticancer applications, the effects of selenium
      nanoparticles on microorganisms remain largely unknown to date. The objective of
      this in vitro study was thus to examine the growth of S. aureus in the presence
      of selenium nanoparticles. Results of this study provided the first evidence of
      strongly inhibited growth of S. aureus in the presence of selenium nanoparticles
      after 3, 4, and 5 hours at 7.8, 15.5, and 31 MUg/mL. The percentage of live
      bacteria also decreased in the presence of selenium nanoparticles. Therefore,
      this study suggests that selenium nanoparticles may be used to effectively
      prevent and treat S. aureus infections and thus should be further studied for
      such applications.

PMID- 21845046
TI  - Receptor-mediated gene delivery by folic acid-modified stearic acid-grafted
      chitosan micelles.
AB  - BACKGROUND: Cationic polymers have been accepted as effective nonviral vectors
      for gene delivery with low immunogenicity unlike viral vectors. However, the lack
      of organ or cell specificity sometimes hampers their application and the
      modification of polymeric vectors has also shown successful improvements in
      achieving cell-specific targeting delivery and in promoting intracellular gene
      transfer efficiency. METHODS: A folic acid-conjugated stearic acid-grafted
      chitosan (FA-CS-SA) micelle, synthesized by a 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide-coupling reaction, was designed for specific receptor-mediated gene
      delivery. RESULTS: Due to the cationic properties of chitosan, the micelles could
      compact the plasmid DNA (pDNA) to form micelle/pDNA complexes nanoparticles. The
      particle size and zeta potential of the FA-CS-SA/pDNA complexes with different
      N/P ratios were 100-200 nm and -20 to -10 mV, respectively. The DNase I
      protection assay indicated that the complexes can efficiently protect condensed
      DNA from enzymatic degradation by DNase I. A cytotoxicity study indicated that
      the micelles exhibited less toxicity in comparison with LipofectamineTM 2000.
      Using SKOV3 and A549 as model tumor cells, the cellular uptake of micelles was
      investigated. CONCLUSION: It was found that cellular uptake of FA-CS-SA in SKOV3
      cells with higher folate receptor expression was faster than that in A549 cells
      with a short incubation time. Luciferase assay and green fluorescent protein
      detection were used to confirm that FA-CS-SA could be an effective gene vector.
      Transfection efficiency of the FA-CS-SA/pDNA complexes in SKOV3 cells was
      enhanced up to 2.3-fold compared with that of the CS-SA/pDNA complexes. However,
      there was no significant difference between the transfection efficiencies of the
      two complexes in A549 cells. Importantly, the transfection efficiency of FA-CS
      SA/pDNA decreased with free FA pretreatment in SKOV3 cells. It was concluded that
      the increase in transfection efficiency of the FA-CS-SA/pDNA complexes was
      attributed to folate receptor-mediated endocytosis.

PMID- 21845047
TI  - Effect of size and processing method on the cytotoxicity of realgar nanoparticles
      in cancer cell lines.
AB  - In this study, the effects of the size and Chinese traditional processing
      (including elutriation, water cleaning, acid cleaning, alkali cleaning) on
      realgar nanoparticles (RN)-induced antitumor activity in human osteosarcoma cell
      lines (MG-63) and hepatoma carcinoma cell lines (HepG-2) were investigated. The
      human normal liver cell line (L-02) was used as control. RN was prepared by high
      energy ball milling technology. The results showed that with the assistance of
      sodium dodecyl sulfate, the size of realgar could be reduced to 127 nm after 12
      hours' ball milling. The surface charge was decreased from 0.83 eV to -17.85 eV
      and the content of As2O3 clearly increased. Except for elutriation, the
      processing methods did not clearly change the size of the RN, but the content of
      As2O3 was reduced dramatically. In vitro MTT tests indicated that in the two
      cancer cell lines, RN cytotoxicity was more intense than that of the coarse
      realgar nanoparticles, and cytotoxicity was typically time- and concentration
      dependent. Also, RN cytotoxicities in the HepG-2 and L-02 cells all increased
      with increasing milling time. Due to the reduction of the As2O3 content, water
      cleaning, acid cleaning, and alkali cleaning decreased RN cytotoxicity in HepG-2,
      but RN after elutriation, with the lowest As2O3 (3.5 mg/g) and the smallest size
      (109.3 nm), showed comparable cytotoxicity in HepG-2 to RN without treatment.
      Meanwhile, RN-induced cytotoxicity in L-02 cells was clearly reduced. Therefore,
      it can be concluded that RN may provide a strong antiproliferation effect in the
      MG-63 and HepG-2 cells. Elutriation processing is a suitable approach to limit
      the dangerous side-effects of As2O3, while maintaining the effectiveness of RN.

PMID- 21845048
TI  - Optimized antimicrobial and antiproliferative activities of titanate nanofibers
      containing silver.
AB  - Titanate nanofibers containing silver have been demonstrated through the
      experiments reported herein to have effective antifungal and antiproliferative
      activities in the presence of UV light. The titanate nanofibers containing silver
      can be fabricated by means of ion exchange followed by a topochemical process in
      an environment suitable for reductive reactions. Excellent antibacterial,
      antifungal, and antiproliferative activities could be demonstrated by both
      Ag2Ti5O11 . xH2O and Ag/titanate (UV light irradiation) due to their unique
      structures and compositions, which have photocatalytic activities to generate
      reactive oxygen species and capabilities to continuously release the silver ions.
      Therefore these materials have the potential to produce a membrane for the
      treatment of superficial malignant tumor, esophageal cancer, or cervical
      carcinoma. They may also hold utility if incorporated into a coating on stents in
      moderate and advanced stage esophageal carcinoma or for endoscopic retrograde
      biliary drainage. These approaches may significantly reduce infections, inhibit
      tumor growth, and importantly, improve quality of life and prolong survival time
      for patients with tumors.

PMID- 21845049
TI  - Histological study of the biodynamics of iron oxide nanoparticles with different
      diameters.
AB  - The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and
      SPIO, respectively) particles that were injected intraperitoneally into 36
      C57BL/6 mice were investigated chronologically. Their distribution was studied
      histologically at six time points by measuring iron-positive areas (MUm2) in
      organ sections stained with Prussian blue. The uptake of the differently sized
      particles was also compared by cultured murine macrophages (J774.1). Iron
      positive areas in the liver were significantly larger in the mice injected with
      USPIO than those injected with SPIO at the first three time points (P < 0.05).
      The amount of USPIO in the lung parenchyma around the airway was larger than that
      of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not
      significantly different. The amount of iron was significantly larger in SPIO-
      than USPIO-treated cultured cells (P < 0.05). In conclusion, it is suggested that
      intra peritoneally injected USPIO particles could be used more quickly than SPIO
      to make Kupffer images of the liver and that both agents could help get lymph
      node images of similar quality.

PMID- 21845050
TI  - Seven years' experience with etidronate in a woman with anorexia nervosa and
      vertebral fractures.
AB  - We report the case of a 30-year-old Japanese woman with anorexia nervosa and
      vertebral fractures who was treated with etidronate. She had a history of
      anorexia nervosa, chronic back pain, osteoporosis, and multiple vertebral
      fractures (morphometric fractures) that responded poorly to treatment with
      alfacalcidol (1 MUg daily) for 1 year and was treated with cyclical etidronate
      (200 mg for 2 weeks every 3 months) for 7 years. The lumbar spine bone mineral
      density (BMD) increased, and the serum alkaline phosphatase and urinary cross
      linked N-terminal telopeptides of type I collagen levels and back pain decreased.
      During the 7-year period of treatment with etidronate, no osteoporotic fractures
      occurred. The patient experienced neither renal dysfunction nor
      hyperparathyroidism caused by osteomalacia. No gastrointestinal tract symptoms
      were observed. Thus, etidronate was effective for increasing the lumbar spine BMD
      and reducing back pain over a 7-year period without causing either osteoporotic
      fractures or adverse events.

PMID- 21845051
TI  - Demonstration of an online tool to assist managed care formulary evidence-based
      decision making: meta-analysis of topical prostaglandin analog efficacy.
AB  - BACKGROUND: The purpose of this paper was to demonstrate the use of an online
      service for conducting a systematic review and meta-analysis of the efficacy of
      topical prostaglandin analogs in reducing intraocular pressure (IOP) in glaucoma
      and ocular hypertension. METHODS: An online service provider (Doctor Evidence)
      reviewed and extracted data from the peer-reviewed literature through September
      2009. Randomized controlled studies of at least three months' duration assessing
      at least two prostaglandin analogs in patients with primary open-angle glaucoma,
      ocular hypertension, or normal-tension glaucoma were included. The primary
      endpoint was mean IOP. Summary estimates were created using random-effects
      models. The Q Chi-square test was used to assess statistical heterogeneity.
      RESULTS: Sixteen studies satisfied the inclusion criteria and were analyzed. On
      average, greater IOP-lowering was seen with bimatoprost relative to latanoprost
      (1 mmHg, P = 0.025) and travoprost (0.8 mmHg, P = 0.033) based on mean IOP after
      12-26 weeks of treatment. No statistical difference was observed in IOP-lowering
      between latanoprost and travoprost (P = 0.841). Findings were similar to
      previously published meta-analyses of topical prostaglandin analogs. CONCLUSION:
      Systematic reviews relying on meta-analytic techniques to create summary
      statistics are considered to be the "gold standard" for synthesizing evidence to
      support clinical decision-making. However, the process is time-consuming, labor
      intensive, and outside the capability of most formulary managers. We have
      demonstrated the effectiveness of a commercial service that facilitates the
      process of conducting such reviews.

PMID- 21845052
TI  - Dexmedetomidine hydrochloride as a long-term sedative.
AB  - Dexmedetomidine undoubtedly is a useful sedative in the intensive care setting
      because it has a minimal effect on the respiratory system. Dexmedetomidine
      infusions lasting more than 24 hours have not been approved since the first
      approval was acquired in the US in 1999. However, in 2008, dexmedetomidine
      infusions for prolonged use were approved in Colombia and in the Dominican
      Republic, and the number of countries that have granted approval for prolonged
      use has been increasing every year. This review discusses the literature
      examining prolonged use of dexmedetomidine and confirms the efficacy and safety
      of dexmedetomidine when it is used for more than 24 hours. Dexmedetomidine was
      administered at varying doses (0.1-2.5 MUg/kg/hour) and durations up to 30 days.
      Dexmedetomidine seems to be an alternative to benzodiazepines or propofol for
      achieving sedation in adults because the incidences of delirium and coma
      associated with dexmedetomidine are lower than the corresponding incidences
      associated with benzodiazepines and propofol, although dexmedetomidine
      administration can cause mild adverse effects such as bradycardia. Controlled
      comparative studies on the efficacy and safety of dexmedetomidine and other
      sedatives in pediatric patients have not been reported. However, dexmedetomidine
      seems to be effective in managing extubation, reducing the use of conventional
      sedatives, and as an alternative for inducing sedation in patients for whom
      traditional sedatives induce inadequate sedation. Prolonged dexmedetomidine
      infusion has not been reported to have any serious adverse effects.
      Dexmedetomidine appears to be an alternative long-term sedative, but further
      studies are needed to establish its efficacy and safety.

PMID- 21845053
TI  - Prolonged-release melatonin for insomnia - an open-label long-term study of
      efficacy, safety, and withdrawal.
AB  - BACKGROUND: Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in
      patients aged 55 years and older. A recent double-blind placebo-controlled study
      demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18-80
      and lack of withdrawal and rebound symptoms upon discontinuation. OBJECTIVE: To
      investigate the efficacy, safety, and withdrawal phenomena associated with 6-12
      months PRM treatment. METHODS: Data from a prospective 6-12-month open-label
      study of 244 community dwelling adults with primary insomnia, who had
      participated in a placebo-controlled, double-blind dose-ranging trial of PRM.
      Patients received PRM nightly, followed by a 2-week withdrawal period. Main
      outcome measures were patient-reported sleep quality ratings (diary), adverse
      events, vital signs, and laboratory tests recorded at each visit, and withdrawal
      symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal
      urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin
      production, was assessed upon discontinuing long-term PRM. RESULTS: Of the 244
      patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96
      completed 12 months of treatment. The mean number of nights by which patients
      reported sleep quality as "good" or "very good" was significantly higher during
      PRM than before treatment. There was no evidence of tolerance to PRM.
      Discontinuation of PRM was not associated with rebound insomnia or withdrawal
      symptoms; on the contrary, residual benefit was observed. PRM was well tolerated,
      and there was no suppression of endogenous melatonin production. CONCLUSION:
      Results support the efficacy and safety of PRM in primary insomnia patients aged
      20-80 throughout 6-12 months of continuous therapy. PRM discontinuation even
      after 12 months was not associated with adverse events, withdrawal symptoms, or
      suppression of endogenous melatonin production.

PMID- 21845055
TI  - Treatment of acute otitis externa with ciprofloxacin otic 0.2% antibiotic ear
      solution.
AB  - BACKGROUND/OBJECTIVE: An inflammation of the cutis and subcutis of the external
      auditory canal is a primary symptom in cases of acute otitis externa. It is
      usually treated locally, since this type of therapy ensures a high concentration
      of the drug and interacts at the site of inflammation with no systemic effects.
      This systematic review compares the efficacy of treatment using a ciprofloxacin
      0.2% solution with other therapeutic options. METHODS: After compiling a catalog
      of search terms, medical databases were searched systematically for randomized,
      controlled studies. This search initially yielded a total of 38 studies which
      were then evaluated by three independent reviewers. The number of studies was
      subsequently reduced to 14: six studies using a ciprofloxacin 0.2% solution, and
      eight studies using both 0.2% and 0.3% solutions. RESULTS: The studies included
      in the review demonstrate the statistical equivalence between the ciprofloxacin
      solution (0.2%) and the reference products PNH (a combination of polymyxin B,
      neomycin sulfate and hydrocortisone), auriculum powder, and a ciprofloxacin foam
      with respect to the cure rate. The research groups consistently observed high in
      vitro activity of ciprofloxacin against Pseudomonas aeruginosa. CONCLUSION: This
      systematic review confirms the hypothesis of ciprofloxacin's noninferiority in
      the treatment of otitis externa, in terms of the cure rate and microbiological
      eradication.

PMID- 21845054
TI  - Current and emerging treatments for the management of myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune neuromuscular disorder. There are several
      treatment options, including symptomatic treatment (acetylcholinesterase
      inhibitors), short-term immunosuppression (corticosteroids), long-term
      immunosuppression (azathioprine, cyclosporine, cyclophosphamide, methotrexate,
      mycophenolate mofetil, rituximab, tacrolimus), rapid acting short-term
      immunomodulation (intravenous immunoglobulin, plasma exchange), and long-term
      immunomodulation (thymectomy). This review explores in detail these different
      treatment options. Potential future treatments are also discussed.

PMID- 21845056
TI  - Bone loss and fractures in multiple sclerosis: focus on epidemiologic and
      physiopathological features.
AB  - Multiple sclerosis (MS) affects the central nervous system leading to disability
      and is complicated by bone loss and fractures. Despite the acceptance of
      osteoporosis and fractures as two major public health problems, in people with MS
      the mechanisms have not been investigated adequately. Physicians and patients
      usually focus on the major cause of disability and neglect the multiple risk
      factors for osteoporosis and fractures in this specific population. This review
      updates the epidemiology and physiopathological mechanisms in MS.

PMID- 21845057
TI  - Looking through the cracks of diabetic candidal balanoposthitis!
AB  - India is becoming an epicentre of type II diabetes mellitus with a crude
      prevalence rate of about 9%. Candida balanoposthitis is a known feature of
      diabetes mellitus especially in Indian males who are predominantly uncircumcised.
      In this country, diabetes is often diagnosed for the first time by
      dermatologists. Diabetes is much more frequently the cause of candida
      balanoposthitis than sexual intercourse in India. Fissuring along with
      balanoposthitis was found to be more common in sexually active males. The
      biomechanical basis of fissuring and the effect of diabetes in this phenomenon
      are explained. The issue of circumcision is debated under various aspects.

PMID- 21845058
TI  - Symptom predictors of response to electroconvulsive therapy in older patients
      with treatment-resistant depression.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) has been used for treatment-resistant
      depression. However, predictors of response to ECT have not been adequately
      studied using the Montgomery and Asberg Depression Rating Scale, especially in
      older patients with treatment-resistant depression. METHODS: This study included
      18 Japanese patients who fulfilled the Diagnostic and Statistical Manual of
      Mental Disorders Fourth Edition Text Revision criteria for a diagnosis of major
      depressive disorder or bipolar disorder with a current major depressive episode,
      and met the definition of treatment-resistant depression outlined by Thase and
      Rush, scoring >=21 on the Montgomery and Asberg Depression Rating Scale. The
      three-factor model of the Montgomery and Asberg Depression Rating Scale was used
      for analysis. Factor 1 was defined by three items, factor 2 by four items, and
      factor 3 by three items, representing dysphoria, retardation, and vegetative
      symptoms, respectively. ECT was performed twice a week for a total of six
      sessions using a Thymatron System IV device with the brief pulse technique.
      Clinical responses were defined on the basis of a >=50% decrease in total
      pretreatment Montgomery and Asberg Depression Rating Scale scores. RESULTS: The
      mean pretreatment factor 2 score for responders (n = 7) was significantly lower
      than that for nonresponders (n = 11). Furthermore, a significant difference in
      mean factor 3 score between responders and nonresponders was observed one week
      after six sessions of ECT, indicating a time lag of response. No significant
      differences were observed for age, number of previous episodes, and duration of
      the current episode between responders and nonresponders. CONCLUSION: This study
      suggests that a low pretreatment factor 2 score is a good predictor of response
      to ECT in older patients with major depression.

PMID- 21845059
TI  - A pilot study on metabolic syndrome and its associated features among Qatari
      schoolchildren.
AB  - AIM: This pilot study aimed to evaluate the individual features of the metabolic
      syndrome (MeS) and its frequency in Qatari schoolchildren aged 6-12 years.
      BACKGROUND: MeS has a strong future risk for development of diabetes and
      cardiovascular diseases. Childhood obesity is increasing the likelihood of MeS in
      children. METHODS: The associated features of MeS were assessed in 67 children.
      They were recruited from the outpatient pediatric clinic at Hamad Medical
      Corporation, Qatar. Height, weight, and waist circumference were measured and
      body mass index was calculated for each child. Fasting blood glucose, total
      cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol and triglycerides (TG) were measured. MeS was defined
      according to the National Cholesterol Education Program Adult Treatment Panel III
      (NCEP-III) which was modified by Cook with adjustment for fasting glucose to
      >=5.6 mM according to recommendations from the American Diabetes Association.
      RESULTS: The overall prevalence of MeS according to NCEP-III criteria was 3.0% in
      children aged 6-12 years. Overweight and obesity was 31.3% in children aged 6-12
      years, according to the International Obesity Task Force criteria. The prevalence
      of MeS was 9.5% in overweight and obese subjects. Increased TG levels represented
      the most frequent abnormality (28.4%) in metabolic syndrome features in all
      subjects, followed by HDL-C (19.4%) in all subjects. CONCLUSION: Increased TG
      levels and low HDL-C were the most frequent components of this syndrome. This
      study showed a significant prevalence of MeS and associated features among
      overweight and obese children. The overall prevalence of MeS in Qatari children
      is in accordance with data from several other countries.

PMID- 21845061
TI  - Effect of hepatic iron concentration and viral factors in chronic hepatitis C
      infected patients with thalassemia major, treated with interferon and ribavirin.
AB  - BACKGROUND: Beta thalassemia major patients are vulnerable to transfusion
      transmitted infection, especially hepatitis C virus (HCV), and iron overload.
      These comorbidities lead to cirrhosis and hepatocellular carcinoma in these
      patients. In order to prevent these complications, treatment of HCV infection and
      regular iron chelating seems to be necessary. The aim of this study was to
      evaluate the effect of hepatic iron concentration (HIC) and viral factors on the
      sustained virological response (SVR) in chronic HCV-infected patients, with beta
      thalassemia major being treated with interferon and ribavirin. MATERIALS AND
      METHODS: We enrolled 30 patients with thalassemia major and chronic HCV who were
      referred to the Hematology Clinic of Guilan University of Medical Sciences,
      between December 2002 and April 2006. HIC was measured by atomic absorption
      spectroscopy before treatment. The viral factors (viral load, genotype) and HIC
      were compared between those who achieved a SVR and nonresponders. RESULTS: Mean
      age of the 30 thalassemic patients, was 22.56 +/- 4.28 years (14-30 years). Most
      patients were male (56.7%). Genotype 1a was seen in 24 (80%) cases. SVR was
      achieved in 15 patients (50%). There were no significant correlations between HIC
      (P = 1.00), viral load (P = 0.414), HCV genotype (P = 0.068), and SVR. No
      difference was observed in viral load (P = 0.669) and HIC (P = 0.654) between
      responders and nonresponders. CONCLUSION: HIC, HCV viral load, and HCV genotype
      were not correlated with virological response, and it seems that there is no need
      to postpone antiviral treatment for more vigorous iron chelating therapy.

PMID- 21845062
TI  - Uterine leiomyoma and its association with menstrual pattern and history of depo
      medroxyprogesterone acetate injections.
AB  - BACKGROUND AND AIM: Despite the high prevalence of uterine leiomyoma, according
      to recent review studies there is uncertainty and a paucity of information
      regarding its predisposing or protective factors. The aim of this study was to
      assess the possible association between menstrual cycle pattern and occurrence of
      surgically treated myomas and also to check if depo-medroxyprogesterone acetate
      (DMPA) injection earlier in reproductive life can affect the later occurrence of
      myomas needing surgical treatment. METHODS: In a case-control study in Ardabil,
      85 women with definite diagnosis of surgically treated uterine leiomyoma and 154
      community controls were enrolled. Possible predictors of myoma including
      menstrual cycle and menstrual bleeding patterns were assessed. Data were analyzed
      using SPSS software (SPSS, IBM, Somers, NY). Odds ratios were used as the main
      statistic in assessing the strength of observed associations. RESULTS: Mean age
      of the participants was 41.8 +/- 8.5 years. Length of menstrual cycle was
      associated with myoma and a higher likelihood of myoma was observed among those
      having shorter menstrual cycles (P < 0.05). Number of menstrual bleeding days was
      also associated with surgically treated myoma and longer bleeding periods
      increased the likelihood of myoma (P < 0.05). Only one of the eight women who had
      a history of depo-medroxyprogesterone acetate injections had developed surgically
      treated uterine leiomyoma and the others belonged to the control group without a
      history of surgical treatment for uterine leiomyoma. CONCLUSION: Menstrual cycle
      pattern is associated with developing leiomyomas requiring surgical treatment.
      DMPA, other than its role in myoma treatment, is also assumed to have a role in
      preventing myomas, but due to the small sample size in this study, larger scale
      prospective trials are needed in the future.

PMID- 21845063
TI  - Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin
      level in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Platelet-derived microparticles (PDMP), selectins, and adiponectin
      play an important role in the development of atherosclerosis in diabetes.
      Miglitol has been shown to have a beneficial effect on postprandial hyperglycemia
      in diabetic patients. However, its influence on platelet activation markers (PDMP
      and soluble CD40 ligand [sCD40L]), selectins, and adiponectin in these patients
      is poorly understood. AIM: We investigated the effect of miglitol on circulating
      levels of PDMP, sCD40L, selectins, and adiponectin in patients with type 2
      diabetes. METHODS: Miglitol (150 mg/day) was administered for 4 months. Levels of
      PDMP, sCD40L, soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin),
      soluble L-selectin (sL-selectin), and adiponectin were measured by enzyme-linked
      immunosorbent assay at baseline, and after 1 and 4 months of treatment. RESULTS:
      The levels of PDMP, sCD40L, sP-selectin, sE-selectin, and sL-selectin were higher
      in diabetic patients than in hypertensive patients, while there were no
      significant differences between hypertensive and hyperlipidemic patients. Before
      miglitol treatment, the adiponectin level of diabetic patients was lower than
      that of hypertensive patients. Miglitol therapy significantly decreased the
      plasma PDMP and sCD40L levels relative to baseline. Miglitol also caused a
      significant decrease of sP-selectin, sE-selectin, and sL-selectin. On the other
      hand, miglitol therapy led to a significant increase in adiponectin after 4
      months of administration compared with baseline. Furthermore, the reduction of
      platelet activation markers and selectins during miglitol therapy was
      significantly greater in the responder (adiponectin-improved) group than the
      nonresponder group of diabetic patients. CONCLUSION: Miglitol has an adiponectin
      dependent anti-atherothrombotic effect that may be beneficial for primary
      prevention of atherothrombosis in patients with type 2 diabetes.

PMID- 21845064
TI  - Gonorrhea infection in women: prevalence, effects, screening, and management.
AB  - Gonorrhea is a set of clinical conditions resulting from infection with the
      sexually-acquired bacterial pathogen Neisseria gonorrhoeae. Acquisition may
      involve multiple mucosal sites in the lower female genital tract, including the
      urethra, cervix, Bartholin's and Skene's glands, as well as the anorectal canal,
      pharynx, and conjunctivae. It may spread to the upper genital tract, uterine
      tubes, abdominal cavity, and other systemic sites. Gonorrhea is the second most
      commonly reported sexually-transmitted infection in the US and rates are higher
      among women than men. Women and infants are affected disproportionately by
      gonorrhea, because early infection may be asymptomatic and also because extension
      of infection is often associated with serious sequelae. Screening is critical for
      infection identification and the prevention or limitation of upper genital tract
      spread, and horizontal and vertical transmission. Routine genital screening is
      recommended annually for all sexually active women at risk for infection,
      including women aged < 25 years and older women with one or more of the following
      risks: a previous gonorrhea infection, the presence of other sexually transmitted
      diseases, new or multiple sex partners, inconsistent condom use, commercial sex
      work, drug use, or human immunodeficiency virus infection with sexual activity or
      pregnancy. Pharyngeal gonococcal infections are common in adolescents, and direct
      culture screening is necessary to identify affected individuals. Nucleic acid
      amplification tests (NAATs) are considered the standard for screening and
      diagnosis. Although urine NAAT testing is most commonly used, there is growing
      support for vaginal swabs collected by providers or patients themselves.
      Resistance to all antibiotics currently recommended for the treatment of
      gonorrhea has been documented and complicates therapeutic strategies. The Centers
      for Disease Control and Prevention recommend treatment of gonorrhea with a single
      class of drugs, ie, the cephalosporins.

PMID- 21845065
TI  - A randomized clinical trial to compare levonorgestrel-releasing intrauterine
      system (Mirena) vs trans-cervical endometrial resection for treatment of
      menorrhagia.
AB  - OBJECTIVE: To compare the acceptability, efficacy, adverse effects, and user
      satisfaction of the levonorgestrel intrauterine system (LNG-IUS) and trans
      cervical resection of the endometrium (TCRE) for the treatment of menorrhagia.
      METHOD: 104 women with menorrhagia were divided into 2 groups: 52 women had the
      LNG-IUS inserted and 52 underwent TCRE. Menstrual pattern, pictorial blood loss
      assessment chart score, adverse effects, and rates of acceptability and
      satisfaction, were recorded at 6 and 12 months after the procedure. RESULTS:
      After a year there were reductions of 93.9% and 88.4% in menstrual blood loss in
      the TCRE and LNG-IUS groups, respectively. Amenorrhea was more common in the TCRE
      group and spotting and systemic effects in the LNG-IUS group. Satisfaction rates
      of the TCRE group were higher than the LNG-IUS group (80.8% vs 69.2%), but the
      difference was not statistically significant. CONCLUSION: Although both
      treatments were found to be equally effective, LNG-IUS was less invasive and can
      be advised for younger women with a desire to preserve fertility.

PMID- 21845066
TI  - Fetal gender ratio in recurrent miscarriages.
AB  - BACKGROUND: The purpose of this study was to evaluate the gender ratio and
      incidence of chromosomal anomalies in the products of conception (POC) from
      recurrent miscarriages. METHODS: We determined the karyotypes of POC from
      patients with recurrent spontaneous miscarriages between 1999 and 2009. RESULTS:
      In total, 313 specimens were successfully karyotyped, with a median gestational
      age of 10 weeks at miscarriage (interquartile range 8-13); 199 (64%) were females
      and 114 (36%) were males. In total, 121 (39%) had abnormal karyotypes, the most
      prevalent of which were chromosome 21 and 16 trisomies, triploidy, and monosomy
      X. CONCLUSION: Our findings suggest that female POC might be more susceptible to
      recurrent miscarriages than male ones during embryogenesis, implantation, and
      initial fetal development.

PMID- 21845067
TI  - Early experience with the da Vinci surgical system robot in gynecological surgery
      at King Abdulaziz University Hospital.
AB  - BACKGROUND: The purpose of this study was to review our experience and the
      challenges of using the da Vinci((r)) surgical system robot during gynecological
      surgery at King Abdulaziz University Hospital. METHODS: A retrospective study was
      conducted to review all cases of robot-assisted gynecologic surgery performed at
      our institution between January 2008 and December 2010. The patients were
      reviewed for indications, complications, length of hospital stay, and conversion
      rate, as well as console and docking times. RESULTS: Over the three-year period,
      we operated on 35 patients with benign or malignant conditions using the robot
      for a total of 62 surgical procedures. The docking times averaged seven minutes.
      The mean console times for simple hysterectomy, bilateral salpingo-oophorectomy,
      and bilateral pelvic lymphadenectomy were 125, 47, and 62 minutes, respectively.
      In four patients, laparoscopic procedures were converted to open procedures,
      giving a conversion rate of 6.5%. All of the conversions were among the first 15
      procedures performed. The average hospital stay was 3 days. Complications
      occurred in five patients (14%), and none were directly related to the robotic
      system. CONCLUSION: Our early experience with the robot show that with proper
      training of the robotic team, technical difficulty with the robotic system is
      limited. There is definitely a learning curve that requires performance of
      gynecological surgical procedures using the robot.

PMID- 21845068
TI  - Twin versus singleton pregnancies: the incidence, pregnancy complications, and
      obstetric outcomes in a Nigerian tertiary hospital.
AB  - BACKGROUND: Twin pregnancy is associated with more pregnancy complications and
      poorer pregnancy outcome than singleton pregnancy. Hence periodic review is
      necessary to improve on the pregnancy outcome. OBJECTIVE: To determine the
      incidence and compare pregnancy complications and obstetric outcomes of twin
      pregnancies and singleton pregnancies. MATERIALS AND METHODS: The twin
      pregnancies (study group) that were delivered at Nnamdi Azikiwe University
      Teaching Hospital (NAUTH), Nnewi, South-East Nigeria from 1st February 2005 to
      31st January 2010 were compared with singleton deliveries (control group) that
      occurred in the same hospital during the same period. RESULTS: A total of 3351
      deliveries were conducted during the study period, of which 113 were twin
      deliveries, giving an incidence of 1:29.6 deliveries. Only 100 case files could
      be retrieved for analysis. The mean parities for the twins and singletons were
      2.7 +/- 2.33 weeks and 1.96 +/- 1.87 weeks whereas the mean gestational age at
      delivery for twin and singleton deliveries were 34 +/- 5.2 weeks and 38.7 +/- 2.4
      weeks respectively (P < 0.05). The mean birth weights were 3.14 +/- 0.73 kg and
      2.3 +/- 1.0 kg for singletons and twins respectively (P < 0.05). Hypertensive
      disorders of pregnancy, cord prolapse, malpresentation, premature rupture of
      membranes, low Apgar scores, cesarean section rate, and perinatal death were
      significantly higher in twin pregnancies than in singleton. CONCLUSION: The
      incidence of twin pregnancy over the study period was high and was significantly
      associated with more pregnancy complications and poorer obstetric outcomes. Close
      antenatal and intrapartum care are needed in order to improve outcome and
      decrease complications.

PMID- 21845069
TI  - Kaposi sarcoma of the adrenal gland resembling epithelioid angiosarcoma: a case
      report.
AB  - Patients with human immunodeficiency virus infection are known to have increased
      risk of various neoplasms, including Kaposi sarcoma, which classically involves
      the skin and mucosal locations. The anaplastic variant of Kaposi sarcoma is rare
      and poorly documented in the literature. It is characterised clinically by a more
      aggressive behaviour and increased metastatic potential, and histologically by
      increased cellularity, mitotic rate, and rarely by epithelioid angiosarcoma-like
      morphology. We report herein a 64-year-old man with a long-standing history of
      human immunodeficiency virus infection who developed a right adrenal tumor with a
      high-grade anaplastic angiosarcoma-like morphology. Immunohistochemistry for
      human herpes virus-8 was strongly positive in the tumor cells. To the best of our
      knowledge, this is the first report of an anaplastic Kaposi sarcoma in the
      adrenal gland.

PMID- 21845070
TI  - One-Year Plasma N-linked Glycome Intra-individual and Inter-individual
      Variability in the Chicken Model of Spontaneous Ovarian Adenocarcinoma.
AB  - Spontaneous epithelial ovarian cancer (EOC) in the chicken presents a similar
      pathogenesis compared with humans including CA-125 expression and genetic
      mutational frequencies (e.g., p53). The high prevalence of spontaneous EOC
      chickens also provides a unique experimental model for biomarker discovery at the
      genomic, proteomic, glycomic, and metabolomic level. In an effort to exploit this
      unique model for biomarker discovery, longitudinal plasma samples were collected
      from chickens at three month intervals for one year. The study described herein
      involved cleaving the N-glycans from these longitudinal chicken plasma samples
      and analyzing them via nanoLC-FTMS/MS. Glycans identified in this study were
      previously found in human plasma and this work provides a promising methodology
      to enable longitudinal studies of the N-linked plasma glycome profile during EOC
      progression. The structure, abundance, and intra-variability and inter
      variability for 35 N-linked glycans identified in this study are reported. The
      full potential of the chicken model for biomarker discovery has yet to be
      realized, but the initial interrogation of longitudinally-procured samples
      provides evidence that supports the value of this strategy in the search for
      glycomic biomarkers.

PMID- 21845071
TI  - Isolation of new 40 microsatellite markers in mandarin fish (Siniperca chuatsi).
AB  - In this study, 23 genomic microsatellite DNA markers and 17 express sequence tag
      (EST)-derived microsatellites were developed and characterized using the fast
      isolation by AFLP of sequences containing repeats (FIASCO) method and data mining
      from public EST databases of mandarin fish (Siniperca chuatsi). These polymorphic
      microsatellite markers were then tested for polymorphism in a wild S. chuatsi
      population. The number of alleles at 23 genomic SSRs varied from 2 to 19 with an
      average of 8.0 alleles per locus. The average observed and expected
      heterozygosities were 0.746 and 0.711, respectively. Of 5361 EST sequences
      examined, 3.9% (209) contain microsatellites, and di-nucleotide repeats are the
      most abundant (67.0%), followed by tri-nucleotide (29.7%) and tetra-nucleotide
      repeats (3.3%). The number of alleles at 17 EST-SSRs varied from 2 to 17 with an
      average of 8.4 alleles per locus. The average observed and expected
      heterozygosities were 0.789 and 0.685, respectively. No significant difference of
      loci polymorphism was found between genomic SSRs and EST-SSRs in terms of number
      of alleles and heterozygosities. Results of cross-species utility indicated that
      13 (52.2%) of the genomic-SSRs and 13 (76.5%) of the EST-SSRs were successfully
      cross-amplified in a related species, the golden mandarin fish (Siniperca
      scherzeri).

PMID- 21845074
TI  - Molecular cloning and characterization of cDNA encoding a putative stress-induced
      heat-shock protein from Camelus dromedarius.
AB  - Heat shock proteins are ubiquitous, induced under a number of environmental and
      metabolic stresses, with highly conserved DNA sequences among mammalian species.
      Camelus dromedaries (the Arabian camel) domesticated under semi-desert
      environments, is well adapted to tolerate and survive against severe drought and
      high temperatures for extended periods. This is the first report of molecular
      cloning and characterization of full length cDNA of encoding a putative stress
      induced heat shock HSPA6 protein (also called HSP70B') from Arabian camel. A full
      length cDNA (2417 bp) was obtained by rapid amplification of cDNA ends (RACE) and
      cloned in pET-b expression vector. The sequence analysis of HSPA6 gene showed
      1932 bp-long open reading frame encoding 643 amino acids. The complete cDNA
      sequence of the Arabian camel HSPA6 gene was submitted to NCBI GeneBank
      (accession number HQ214118.1). The BLAST analysis indicated that C. dromedaries
      HSPA6 gene nucleotides shared high similarity (77-91%) with heat shock gene
      nucleotide of other mammals. The deduced 643 amino acid sequences (accession
      number ADO12067.1) showed that the predicted protein has an estimated molecular
      weight of 70.5 kDa with a predicted isoelectric point (pI) of 6.0. The
      comparative analyses of camel HSPA6 protein sequences with other mammalian heat
      shock proteins (HSPs) showed high identity (80-94%). Predicted camel HSPA6
      protein structure using Protein 3D structural analysis high similarities with
      human and mouse HSPs. Taken together, this study indicates that the cDNA
      sequences of HSPA6 gene and its amino acid and protein structure from the Arabian
      camel are highly conserved and have similarities with other mammalian species.

PMID- 21845072
TI  - Teucrium plant species as natural sources of novel anticancer compounds:
      antiproliferative, proapoptotic and antioxidant properties.
AB  - This study deals with total phenolic content, antiproliferative and proapoptotic
      activity of methanolic extracts from different Teucrium species and the effect on
      the prooxidant/antioxidant status in HCT-116 cells. The total phenolic content of
      the extracts was measured spectrophotometricaly and the obtained results ranged
      from 56.62 mg/g to 172.50 mg GA/g. The antiproliferative activity of methanolic
      extracts from different Teucrium species was determined using MTT cell viability
      assay, where IC(50) value was used as a parameter for cytotoxicity. The type of
      cell death was explored by fluorescence microscopy using the acridin
      orange/ethidium bromide method. MTT assay showed that all extracts significantly
      reduced cell viability in a dose-dependent manner, with very low IC(50) values.
      The highest content of phenolic compounds and the best cytotoxic activity on HCT
      116 cells after 24 h of exposure was in T. chamaedrys extract, with IC(50) values
      of 5.48 * 10(-9) MUg/mL. After 72 h, methanolic extract of T. arduini appeared to
      have the best cytotoxic activity on HCT-116, with IC(50) values of 0.37 MUg/mL.
      Treatments caused typical apoptotic morphological changes in HCT-116 cells and
      showed a high percentage of apoptotic cells. The results of the presented
      research indicate that some Teucrium extracts are a very rich source of phenols,
      which may directly contribute to high antiproliferative and proapoptotic
      activity.

PMID- 21845075
TI  - A novel preparation method for camptothecin (CPT) loaded folic acid conjugated
      dextran tumor-targeted nanoparticles.
AB  - In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted
      nanoparticles were produced with a supercritical antisolvent (SAS) technique by
      using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an
      antisolvent. A factorial design was used to reveal the effect of various process
      parameters on the mean particle size (MPS) and morphology of the particles
      formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a
      MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading
      efficiency were 62.13% and 36.12%, respectively. It was found that the
      concentrations of the camptothecin (CPT) and dextran solution had a major
      influence upon morphology and shape of the final product. In addition, the
      samples were characterized by Scanning electron microscopy (SEM), Fourier
      transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC)
      and X-ray diffraction (XRD) with the purpose of developing a suitable targeted
      drug delivery system for cancer chemotherapy.

PMID- 21845073
TI  - Reciprocal roles of angiotensin II and Angiotensin II Receptors Blockade (ARB) in
      regulating Cbfa1/RANKL via cAMP signaling pathway: possible mechanism for
      hypertension-related osteoporosis and antagonistic effect of ARB on hypertension
      related osteoporosis.
AB  - Hypertension is a risk factor for osteoporosis. Animal and epidemiological
      studies demonstrate that high blood pressure is associated with increased calcium
      loss, elevated parathyroid hormone, and increased calcium movement from bone.
      However, the mechanism responsible for hypertension-related osteoporosis remains
      elusive. Recent epidemiological studies indicate the benefits of Angiotensin II
      Receptors Blockade (ARB) on decreasing fracture risks. Since receptors for
      angiotensin II, the targets of ARB, are expressed in both osteoblasts and
      osteoclasts, we postulated that angiotensin II plays an important role in
      hypertension-related osteoporosis. Cbfa1 and RANKL, the important factors for
      maintaining bone homeostasis and key mediators in controlling osteoblast and
      osteoclast differentiation, are both regulated by cAMP-dependent signaling.
      Angiotensin II along with factors such as LDL, HDL, NO and homocysteine that are
      commonly altered both in hypertension and osteoporosis, can down-regulate the
      expression of Cbfa1 but up-regulate RANKL expression via the cAMP signaling
      pathway. We thus hypothesized that, by altering the ratio of Cbfa1/RANKL
      expression via the cAMP-dependent pathway, angiotensin II differently regulates
      osteoblast and osteoclast differentiation leading to enhanced bone resorption and
      reduced bone formation. Since ARB can antagonize the adverse effect of
      angiotensin II on bone by lowering cAMP levels and modifying other downstream
      targets, including LDL, HDL, NO and Cbfa1/RANKL, we propose the hypothesis that
      the antagonistic effects of ARB may also be exerted via cAMP signaling pathway.

PMID- 21845076
TI  - Biodegradable metals for cardiovascular stent application: interests and new
      opportunities.
AB  - During the last decade, biodegradable metallic stents have been developed and
      investigated as alternatives for the currently-used permanent cardiovascular
      stents. Degradable metallic materials could potentially replace corrosion
      resistant metals currently used for stent application as it has been shown that
      the role of stenting is temporary and limited to a period of 6-12 months after
      implantation during which arterial remodeling and healing occur. Although
      corrosion is generally considered as a failure in metallurgy, the corrodibility
      of certain metals can be an advantage for their application as degradable
      implants. The candidate materials for such application should have mechanical
      properties ideally close to those of 316L stainless steel which is the gold
      standard material for stent application in order to provide mechanical support to
      diseased arteries. Non-toxicity of the metal itself and its degradation products
      is another requirement as the material is absorbed by blood and cells. Based on
      the mentioned requirements, iron-based and magnesium-based alloys have been the
      investigated candidates for biodegradable stents. This article reviews the recent
      developments in the design and evaluation of metallic materials for biodegradable
      stents. It also introduces the new metallurgical processes which could be applied
      for the production of metallic biodegradable stents and their effect on the
      properties of the produced metals.

PMID- 21845077
TI  - A rapid method for optimizing running temperature of electrophoresis through
      repetitive on-chip CE operations.
AB  - In this paper, a rapid and simple method to determine the optimal temperature
      conditions for denaturant electrophoresis using a temperature-controlled on-chip
      capillary electrophoresis (CE) device is presented. Since on-chip CE operations
      including sample loading, injection and separation are carried out just by
      switching the electric field, we can repeat consecutive run-to-run CE operations
      on a single on-chip CE device by programming the voltage sequences. By utilizing
      the high-speed separation and the repeatability of the on-chip CE, a series of
      electrophoretic operations with different running temperatures can be
      implemented. Using separations of reaction products of single-stranded DNA
      (ssDNA) with a peptide nucleic acid (PNA) oligomer, the effectiveness of the
      presented method to determine the optimal temperature conditions required to
      discriminate a single-base substitution (SBS) between two different ssDNAs is
      demonstrated. It is shown that a single run for one temperature condition can be
      executed within 4 min, and the optimal temperature to discriminate the SBS could
      be successfully found using the present method.

PMID- 21845078
TI  - Preparation and characterization of catalase-loaded solid lipid nanoparticles
      protecting enzyme against proteolysis.
AB  - Catalase-loaded solid lipid nanoparticles (SLNs) were prepared by the double
      emulsion method (w/o/w) and solvent evaporation techniques, using
      acetone/methylene chloride (1:1) as an organic solvent, lecithin and triglyceride
      as oil phase and Poloxmer 188 as a surfactant. The optimized SLN was prepared by
      lecithin: triglyceride ratio (5%), 20-second + 30-second sonication, and 2%
      Poloxmer 188. The mean particle size of SLN was 296.0 +/- 7.0 nm, polydispersity
      index range and zeta potential were 0.322-0.354 and -36.4 +/- 0.6, respectively,
      and the encapsulation efficiency reached its maximum of 77.9 +/- 1.56. Catalase
      distributed between the solid lipid and inner aqueous phase and gradually
      released from Poloxmer coated SLNs up to 20% within 20 h. Catalase-loaded SLN
      remained at 30% of H(2)O(2)-degrading activity after being incubated with
      Proteinase K for 24 h, while free catalase lost activity within 1 h.

PMID- 21845079
TI  - Controlled delivery of gentamicin using poly(3-hydroxybutyrate) microspheres.
AB  - Poly(3-hydroxybutyrate), P(3HB), produced from Bacillus cereus SPV using a simple
      glucose feeding strategy was used to fabricate P(3HB) microspheres using a solid
      in-oil-water (s/o/w) technique. For this study, several parameters such as
      polymer concentration, surfactant and stirring rates were varied in order to
      determine their effect on microsphere characteristics. The average size of the
      microspheres was in the range of 2 MUm to 1.54 MUm with specific surface areas
      varying between 9.60 m(2)/g and 6.05 m(2)/g. Low stirring speed of 300 rpm
      produced slightly larger microspheres when compared to the smaller microspheres
      produced when the stirring velocity was increased to 800 rpm. The surface
      morphology of the microspheres after solvent evaporation appeared smooth when
      observed under SEM. Gentamicin was encapsulated within these P(3HB) microspheres
      and the release kinetics from the microspheres exhibiting the highest
      encapsulation efficiency, which was 48%, was investigated. The in vitro release
      of gentamicin was bimodal, an initial burst release was observed followed by a
      diffusion mediated sustained release. Biodegradable P(3HB) microspheres developed
      in this research has shown high potential to be used in various biomedical
      applications.

PMID- 21845080
TI  - Molecular characterization of Tob1 in muscle development in pigs.
AB  - Cell proliferation is an important biological process during myogenesis. Tob1
      encoded a member of the Tob/BTG family of anti-proliferative proteins. Our
      previous LongSAGE (Long Serial Analysis of Gene Expression) analysis suggested
      that Tob1 was differentially expressed during prenatal skeletal muscle
      development. In this study, we isolated and characterized the swine Tob1 gene.
      Subsequently, we examined Tob1 chromosome assignment, subcellular localization
      and dynamic expression profile in prenatal skeletal muscle (33, 65 and 90 days
      post-conception, dpc) from Landrace (lean-type) and Tongcheng pigs (obese-type).
      The Tob1 gene was mapped to pig chromosome 12 (SSC12). The Tob1 protein was
      distributed throughout the nucleus and cytoplasm of PK15 cells. During prenatal
      skeletal muscle development, Tob1 was up-regulated and highly expressed in
      skeletal muscle at 90 dpc in Tongcheng pigs but peaked at 65 dpc in Landrace
      pigs. This result suggested that there were different proliferation patterns
      during myogenesis between Tongcheng and Landrace pigs. During postnatal skeletal
      muscle development, the expression of Tob1 increased with aging, indicating that
      the proliferation potential of myoblasts decreased in postnatal muscle
      development. In tissues of adult wuzhishan miniature pigs, the Tob1 gene was
      highly expressed in skeletal muscle. The expression of Tob1 was significantly
      increased at day 6 during C2C12 differentiation time, suggesting a possible role
      in skeletal muscle development. Therefore, this study indicated that Tob1 perhaps
      played an important role in skeletal muscle development.

PMID- 21845082
TI  - Predictivity approach for quantitative structure-property models. Application for
      blood-brain barrier permeation of diverse drug-like compounds.
AB  - The goal of the present research was to present a predictivity statistical
      approach applied on structure-based prediction models. The approach was applied
      to the domain of blood-brain barrier (BBB) permeation of diverse drug-like
      compounds. For this purpose, 15 statistical parameters and associated 95%
      confidence intervals computed on a 2 * 2 contingency table were defined as
      measures of predictivity for binary quantitative structure-property models. The
      predictivity approach was applied on a set of compounds comprised of 437 diverse
      molecules, 122 with measured BBB permeability and 315 classified as active or
      inactive. A training set of 81 compounds (~2/3 of 122 compounds assigned
      randomly) was used to identify the model and a test set of 41 compounds was used
      as the internal validation set. The molecular descriptor family on vertices
      cutting was the computation tool used to generate and calculate structural
      descriptors for all compounds. The identified model was assessed using the
      predictivity approach and compared to one model previously reported. The best
      identified classification model proved to have an accuracy of 69% in the training
      set (95%CI [58.53-78.37]) and of 73% in the test set (95%CI [58.32-84.77]). The
      predictive accuracy obtained on the external set proved to be of 73% (95%CI
      [67.58-77.39]). The classification model proved to have better abilities in the
      classification of inactive compounds (specificity of ~74% [59.20-85.15]) compared
      to abilities in the classification of active compounds (sensitivity of ~64%
      [48.47-77.70]) in the training and external sets. The overall accuracy of the
      previously reported model seems not to be statistically significantly better
      compared to the identified model (~81% [71.45-87.80] in the training set, ~93%
      [78.12-98.17] in the test set and ~79% [70.19-86.58] in the external set). In
      conclusion, our predictivity approach allowed us to characterize the model
      obtained on the investigated set of compounds as well as compare it with a
      previously reported model. According to the obtained results, the reported model
      should be chosen if a correct classification of inactive compounds is desired and
      the previously reported model should be chosen if a correct classification of
      active compounds is most wanted.

PMID- 21845083
TI  - Novel recovery of nano-structured ceria (CeO(2)) from Ce(III)-benzoxazine dimer
      complexes via thermal decomposition.
AB  - N,N-bis(2-hydroxybenzyl)alkylamines, benzoxazine dimers, are the major product
      produced from benzoxazine monomers on mono-functional phenol by the one step ring
      opening reaction. Due to the metal responsive property of benzoxazine dimers, in
      this present work, N,N-bis(5-methyl-2-hydroxybenzyl)methylamine (MMD), N,N-bis (5
      ethyl-2-hydroxybenzyl)methylamine (EMD), and N,N-bis(5-methoxy-2-hydroxybenzyl)
      methyl amine (MeMD), are considered as novel ligands for rare earth metal ion,
      such as cerium(III) ion. The complex formed when the clear and colorless
      solutions of cerium nitrate and benzoxazine dimers were mixed, results in a brown
      colored solution. The metal-ligand ratios determined by the molar ratio and the
      Job's methods were found to be in a ratio of 1:6. To clarify the evidence of the
      complex formation mechanism, the interactions among protons in benzoxazine dimers
      both prior to and after the formation of complexes were determined by means of
      (1)H-NMR, 2D-NMR and a computational simulation. The single phase ceria (CeO(2))
      was successfully prepared by thermal decomposition of the Ce(III)-benzoxazine
      dimer complexes at 600  degrees C for 2 h, was then characterized using XRD. In
      addition, the ceria powder investigated by TEM is spherical with an average
      diameter of 20 nm.

PMID- 21845081
TI  - To remove or not to remove? The challenge of extracting the template to make the
      cavities available in Molecularly Imprinted Polymers (MIPs).
AB  - Template removal is a critical step in the preparation of most molecularly
      imprinted polymers (MIPs). The polymer network itself and the affinity of the
      imprinted cavities for the template make its removal hard. If there are remaining
      template molecules in the MIPs, less cavities will be available for rebinding,
      which decreases efficiency. Furthermore, if template bleeding occurs during
      analytical applications, errors will arise. Despite the relevance to the MIPs
      performance, template removal has received scarce attention and is currently the
      least cost-effective step of the MIP development. Attempts to reach complete
      template removal may involve the use of too drastic conditions in conventional
      extraction techniques, resulting in the damage or the collapse of the imprinted
      cavities. Advances in the extraction techniques in the last decade may provide
      optimized tools. The aim of this review is to analyze the available data on the
      efficiency of diverse extraction techniques for template removal, paying
      attention not only to the removal yield but also to MIPs performance. Such an
      analysis is expected to be useful for opening a way to rational approaches for
      template removal (minimizing the costs of solvents and time) instead of the
      current trial-and-error methods.

PMID- 21845084
TI  - Genetic diversity and differentiation of the orange-spotted grouper (Epinephelus
      coioides) between and within cultured stocks and wild populations inferred from
      microsatellite DNA analysis.
AB  - In the present study, we employed microsatellite DNA markers to analyze the
      genetic diversity and differentiation between and within cultured stocks and wild
      populations of the orange-spotted grouper originating from the South China Sea
      and Southeast Asia. Compared to wild populations, genetic changes including
      reduced genetic diversity and significant differentiation have taken place in
      cultured grouper stocks, as shown by allele richness and heterozygosity studies,
      pairwise F(st), structure, molecular variance analysis, as well as
      multidimensional scaling analysis. Although two geographically adjacent orange
      spotted grouper populations in China showed negligible genetic divergence,
      significant population differentiation was observed in wild grouper populations
      distributed in a wide geographical area from China, through Malaysia to
      Indonesia. However, the Mantel test rejected the isolation-by-distance model of
      genetic structure, which indicated the genetic differentiation among the
      populations could result from the co-effects of various factors, such as
      historical dispersal, local environment, ocean currents, river flows and island
      blocks. Our results demonstrated that microsatellite markers could be suitable
      not only for genetic monitoring cultured stocks but also for revealing the
      population structuring of wild orange-spotted grouper populations. Meanwhile, our
      study provided important information for breeding programs, management of
      cultured stocks and conservation of wild populations of the orange-spotted
      grouper.

PMID- 21845085
TI  - Enabling anticancer therapeutics by nanoparticle carriers: the delivery of
      Paclitaxel.
AB  - Anticancer drugs, such as paclitaxel (PTX), are indispensable for the treatment
      of a variety of malignancies. However, the application of most drugs is greatly
      limited by the low water solubility, poor permeability, or high efflux from
      cells. Nanoparticles have been widely investigated to enable drug delivery due to
      their low toxicity, sustained drug release, molecular targeting, and additional
      therapeutic and imaging functions. This review takes paclitaxel as an example and
      compares different nanoparticle-based delivery systems for their effectiveness in
      cancer chemotherapy.

PMID- 21845086
TI  - Isoniazid proliposome powders for inhalation-preparation, characterization and
      cell culture studies.
AB  - The aims of this study were to develop proliposome powders containing isoniazid
      (INH) in a dry powder aerosol form. INH-proliposome powders were prepared by a
      spray drying method. Proliposome physicochemical properties were determined using
      cascade impactor, X-ray diffraction and differential scanning calorimetry. The
      toxicity of proliposomes to respiratory-associated cell lines and its potential
      to provoke immunological responses from alveolar macrophages (AM) were
      determined. Free INH and INH-proliposome bioactivities were tested in vitro and
      in AM infected with Mycobacterium bovis (M. bovis). Aerosolization properties of
      INH-proliposome powders at 60 L/min, the powders showed mass median aerodynamic
      diameters of 2.99-4.92 MUm, with fine particle fractions (aerosolized particles
      less than 4.4 MUm) of 15-35%. Encapsulation of INH was 18-30%. Proliposome
      formulations containing INH to mannitol ratios of 4:6 and 6:4 exhibited the
      greatest overlapping peak between the drug and mannitol. INH-proliposomes were
      evidently nontoxic to respiratory-associated cells, and did not activate AM to
      produce inflammatory mediators-including interleukin-1beta (IL-1beta), tumor
      necrosis factor-alpha (TNF-alpha), and nitric oxide-at a toxic level. The
      efficacy of INH-proliposome against AM infected with M. bovis was significantly
      higher than that of free INH (p < 0.05). INH-proliposomes are potential
      candidates for an alternative tuberculosis treatment.

PMID- 21845087
TI  - Isolation and characterization of microsatellite loci in the Chinese Cobra Naja
      atra (Elapidae).
AB  - We characterize thirteen polymorphic microsatellite loci isolated from Naja atra
      genomic libraries, which were enriched for AC-motif microsatellites. The thirteen
      loci were screened on a group of 48 individuals from two populations, one in
      Yong'an and the other in Ganzhou. These markers revealed a relatively high degree
      of genetic diversity (4-12 alleles per locus) and heterozygosity (Ho ranged from
      0.213-0.854 and He ranged from 0.301-0.838). Tests for departure from Hardy
      Weinberg equilibrium and for linkage disequilibrium were conducted for each of
      the two populations separately. After sequential Bonferroni correction, none of
      the 13 loci showed significant departures from Hardy-Weinberg equilibrium.
      Hierarchical analysis of molecular variance indicated that a small but
      significant (P < 0.001) proportion (16.0%) of the total variation in the
      microsatellite DNA data were attributable to differences among populations,
      indicating geographical structuring and restricted gene flow. It could be
      attributable to the Wuyi mountains in the area having a sufficiently isolating
      effect to significantly reduce gene flow. Our microsatellite data also showed a
      low N(m) (1.31) value in the two populations from mainland China. Thus, the
      Yong'an and Ganzhou populations could be treated as distinct evolutionarily
      significant units (ESUs). The high level of polymorphism revealed by these
      microsatellite markers will be useful for the study of gene flow, population
      structure and evolutionary history of N. atra.

PMID- 21845088
TI  - Klebsiella pneumoniae yggG gene product: a zinc-dependent metalloprotease.
AB  - Klebsiella pneumoniae causes neonatal sepsis and nosocomial infections. One of
      the strains, K. pneumoniae MGH 78578, shows high level of resistance to multiple
      microbial agents. In this study, domain family, amino acid sequence and topology
      analyses were performed on one of its hypothetical protein, YggG (KPN_03358).
      Structural bioinformatics approaches were used to predict the structure and
      functionality of YggG protein. The open reading frame (ORF) of yggG, which was a
      putative metalloprotease gene, was also cloned, expressed and characterized. The
      ORF was PCR amplified from K. pneumoniae MGH 78578 genomic DNA and cloned into a
      pET14-b vector for heterologous expression in Escherichia coli. The purified YggG
      protein was subsequently assayed for casein hydrolysis under different
      conditions. This protein was classified as peptidase M48 family and subclan
      gluzincin. It was predicted to contain one transmembrane domain by TMpred.
      Optimal protein expression was achieved by induction with 0.6 mM isopropyl
      thiogalactoside (IPTG) at 25  degrees C for six hours. YggG was purified as
      soluble protein and confirmed to be proteolytically active under the presence of
      1.25 mM zinc acetate and showed optimum activity at 37  degrees C and pH 7.4. We
      confirmed for the first time that the yggG gene product is a zinc-dependent
      metalloprotease.

PMID- 21845089
TI  - Silkworm hemolymph down-regulates the expression of endoplasmic reticulum
      chaperones under radiation-irradiation.
AB  - We demonstrated that up-regulation of gene expression of endoplasmic reticulum
      (ER) chaperones (BiP, calnexin, calreticulin, ERp29) and ER membrane kinases
      (IRE1, PERK, ATF6) was induced by radiation in neuronal PC12 cells. However,
      addition of silkworm, Bombyx mori, hemolymph to irradiated cells resulted in an
      obvious decrease in expression of these genes, compared with a single radiation
      treatment. In contrast, one of the ER chaperones, "ischemia-responsive protein 94
      kDa" (irp94), was up-regulated by radiation. However, addition of silkworm
      hemolymph resulted in no change in the expression of irp94, with an expression
      pattern that differed from that of ER chaperones. Based on these results, we
      propose that silkworm hemolymph contains factors that regulate a decrease in the
      expression of ER chaperones under radiation-irradiation conditions, with the
      exception of irp94, which is not down-regulated. We suggest that this difference
      in the molecular character of irp94 may provide a clue to the biological
      functions associated with ER stress pathways, particularly the effects of
      radiation.

PMID- 21845091
TI  - Interactions of antibiotics and methanolic crude extracts of Afzelia Africana
      (Smith.) against drug resistance bacterial isolates.
AB  - Infection due to multidrug resistance pathogens is difficult to manage due to
      bacterial virulence factors and because of a relatively limited choice of
      antimicrobial agents. Thus, it is imperative to discover fresh antimicrobials or
      new practices that are effective for the treatment of infectious diseases caused
      by drug-resistant microorganisms. The objective of this experiment is to
      investigate for synergistic outcomes when crude methanolic extract of the stem
      bark of Afzelia africana and antibiotics were combined against a panel of
      antibiotic resistant bacterial strains that have been implicated in infections.
      Standard microbiological protocols were used to determine the minimum inhibitory
      concentrations (MICs) of the extract and antibiotics, as well as to investigate
      the effect of combinations of the methanolic extract of A. africana stem bark and
      selected antibiotics using the time-kill assay method. The extract of Afzelia
      africana exhibited antibacterial activities against both Gram-negative and Gram
      positive bacteria made up of environmental and standard strains at a screening
      concentration of 5 mg/mL. The MICs of the crude extracts and the antibiotics
      varied between 1 MUg/mL and 5.0 mg/mL. Overall, synergistic response constituted
      about 63.79% of all manner of combinations of extract and antibiotics against all
      test organisms; antagonism was not detected among the 176 tests carried out. The
      extract from A. africana stem bark showed potentials of synergy in combination
      with antibiotics against strains of pathogenic bacteria. The detection of synergy
      between the extract and antibiotics demonstrates the potential of this plant as a
      source of antibiotic resistance modulating compounds.

PMID- 21845090
TI  - Epigenetic therapy for breast cancer.
AB  - Both genetic and epigenetic alterations can control the progression of cancer.
      Genetic alterations are impossible to reverse, while epigenetic alterations are
      reversible. This advantage suggests that epigenetic modifications should be
      preferred in therapy applications. DNA methyltransferases and histone
      deacetylases have become the primary targets for studies in epigenetic therapy.
      Some DNA methylation inhibitors and histone deacetylation inhibitors are approved
      by the US Food and Drug Administration as anti-cancer drugs. Therefore, the uses
      of epigenetic targets are believed to have great potential as a lasting favorable
      approach in treating breast cancer.

PMID- 21845092
TI  - Steady state-Hopf mode interactions at the onset of electroconvection in the
      nematic liquid crystal Phase V.
AB  - We report on a new mode interaction found in electroconvection experiments on the
      nematic liquid crystal mixture Phase V in planar geometry. The mode interaction
      (codimension two) point occurs at a critical value of the frequency of the
      driving AC voltage. For frequencies below this value the primary pattern-forming
      instability at the onset voltage is an oblique stationary instability involving
      oblique rolls, and above this value it is an oscillatory instability giving rise
      to normal traveling rolls (oriented perpendicular to and traveling in the
      director direction). The transition has been confirmed by measuring the roll
      angle and the dominant frequency of the time series, as both quantities exhibit a
      discontinuous jump across zero when the AC frequency is varied near threshold.
      The globally coupled system of Ginzburg-Landau equations that qualitatively
      describe this mode interaction is constructed, and the resulting normal form, in
      which slow spatial variations of the mode amplitudes are ignored, is analyzed.
      This analysis shows that the Ginzburg-Landau system provides the adequate
      theoretical description for the experimentally observed phenomenon. The
      experimentally observed patterns at and higher above the onset allow us to narrow
      down the range of the parameters in the normal form.

PMID- 21845094
TI  - Antiviral activity and mechanism of action of novel thiourea containing chiral
      phosphonate on tobacco mosaic virus.
AB  - Using half-leaf method O,O'-diisopropyl (3-(L-1-(benzylamino)-1-oxo-3-
      phenylpropan-2-yl)thioureido)(phenyl)methyl phosphonate (2009104) was studied for
      its activity on tobacco mosaic virus (TMV). It showed good curative activity in
      vivo and the curative activity at 500 MUg/mL was found to be 53.3%. In vivo
      treatment with the control agent Ningnanmycin at 500 MUg/mL resulted in 51.2%
      inhibition and curative inhibition rates respectively. Dot-ELISA test was
      employed to verify the efficacy of activity of compound 200910 for anti-TMV
      activity. The mechanism of action of compound 2009104 to resist TMV was also
      studied. The results showed that the resistance enzymes PAL, POD, SOD activity
      and chlorophyll content after TMV inoculation K(326) (Nicotiana tabacum K(326))
      of tobacco plants followed by treatment with compound 2009104 were significantly
      enhanced. The study of the effect of compound 2009104 on TMV capsid protein (CP)
      showed that it inhibited the polymerization process of TMV-CP in vitro.

PMID- 21845095
TI  - Variations in content and extractability of durum wheat (Triticum turgidum L. var
      durum) Arabinoxylans associated with genetic and environmental factors.
AB  - Arabinoxylans (AX) represent the most abundant components of non-starch
      polysaccharides in wheat, constituting about 70% of cell wall polysaccharides. An
      important property of AX is their ability to form highly viscous water solutions;
      this peculiarity has a significant impact on the technological characteristics of
      wheat and determines the physiologically positive influence in consumption. Durum
      wheat (Triticum turgidum L. var durum), the raw material for pasta production, is
      one of the most important crops in Italy. As part of a large project aimed at
      improving durum wheat quality, the characterization of the nutritional and
      technological aspects of whole grains was considered. Particular attention was
      addressed to identify the best suited genotypes for the production of innovative
      types of pasta with enhanced functional and organoleptic properties. The
      objective of the present study was to investigate the genetic variability of AX
      by examining a group of durum wheat genotypes collected at two localities in
      Italy for two consecutive years. The environmental influence on AX content and
      extractability was also evaluated. Variability in the AX fraction contents was
      observed; the results indicated that AX fractions of durum wheat grain can be
      affected by the genotype and environment characteristics and the different
      contribution of genotype and environment to total variation was evidenced. The
      genotype * environment (G * E) interaction was significant for all examined
      traits, the variations due to G * E being lower than that of genotype or
      environment. The data and the statistical analysis allowed identification of the
      Italian durum wheat varieties that were consistently higher in total
      arabinoxilans; in addition, principal component analysis biplots illustrated that
      for arabinoxylan fractions some varieties responded differently in various
      environment climatic conditions.

PMID- 21845093
TI  - Putative biomarkers and targets of estrogen receptor negative human breast
      cancer.
AB  - Breast cancer is a progressive and potentially fatal disease that affects women
      of all ages. Like all progressive diseases, early and reliable diagnosis is the
      key for successful treatment and annihilation. Biomarkers serve as indicators of
      pathological, physiological, or pharmacological processes. Her2/neu, CA15.3,
      estrogen receptor (ER), progesterone receptor (PR), and cytokeratins are
      biomarkers that have been approved by the Food and Drug Administration for
      disease diagnosis, prognosis, and therapy selection. The structural and
      functional complexity of protein biomarkers and the heterogeneity of the breast
      cancer pathology present challenges to the scientific community. Here we review
      estrogen receptor-related putative breast cancer biomarkers, including those of
      putative breast cancer stem cells, a minor population of estrogen receptor
      negative tumor cells that retain the stem cell property of self-renewal. We also
      review a few promising cytoskeleton targets for ER alpha negative breast cancer.

PMID- 21845096
TI  - Bioactivities from marine algae of the genus Gracilaria.
AB  - Seaweeds are an important source of bioactive metabolites for the pharmaceutical
      industry in drug development. Many of these compounds are used to treat diseases
      like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain,
      arthritis, as well as viral, bacterial, and fungal infections. This paper offers
      a survey of the literature for Gracilaria algae extracts with biological
      activity, and identifies avenues for future research. Nineteen species of this
      genus that were tested for antibacterial, antiviral, antifungal,
      antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory
      activities are cited from the 121 references consulted.

PMID- 21845097
TI  - Variations of antioxidant properties and NO scavenging abilities during
      fermentation of tea.
AB  - Tea is known as one of the most popular beverages in the world, which is believed
      to be beneficial for health. The main components in tea will change a lot
      depending on the different processes of fermentation, and thus the effects of
      different teas on human health may differ. The aim of this study is to explore
      the varied abilities of reactive oxygen species (ROS) and nitric oxide (NO)
      scavenging during the fermentation of tea. In this study, we conducted the in
      vitro experiments which involved some reaction systems indicating the abilities
      of scavenging ROS and NO. We also investigated the effects of tea and their
      components (catechins, theabrownins, caffeine) on the intracellular levels of ROS
      and NO, using Raw 264.7 cells as the model. We found that regardless of whether
      it was out of cell system or in Raw 264.7 cells, the abilities of scavenging ROS
      would decrease during the fermentation of tea. Further, the post-fermented pu-erh
      tea showed the best effect on inhibiting the lipopolysaccharide (LPS)-induced
      production of NO. These findings indicated that the fermentation process caused a
      change of the components which might be due to the changes of their antioxidant
      properties and NO scavenging abilities.

PMID- 21845098
TI  - Enhanced anti-tumoral activity of methotrexate-human serum albumin conjugated
      nanoparticles by targeting with Luteinizing Hormone-Releasing Hormone (LHRH)
      peptide.
AB  - Active targeting could increase the efficacy of anticancer drugs. Methotrexate
      human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone
      releasing hormone (LHRH) as targeting moieties, with the aim of specifically
      targeting the cancer cells, were prepared. Owing to the high expression of LHRH
      receptors in many cancer cells as compared to normal cells, LHRH was used as the
      targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via
      a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle
      size between 120-138 nm were prepared. The cytotoxicity of LHRH targeted and non
      targeted nanoparticles were determined on the LHRH positive and negative cell
      lines. The internalization of the targeted and non-targeted nanoparticles in LHRH
      receptor positive and negative cells was investigated using flow cytometry
      analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted
      nanoparticles on the LHRH receptor positive cells were significantly more than
      non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by
      LHRH receptor positive cells significantly more than non-targeted nanoparticles.
      There were no significant differences between the uptake of targeted and non
      targeted nanoparticles to the LHRH receptor negative cells. The active targeting
      procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti
      tumoral activity of MTX.

PMID- 21845099
TI  - Identification and categorization of liver toxicity markers induced by a related
      pair of drugs.
AB  - Drug-induced liver injury (DILI) is the primary adverse event that results in the
      withdrawal of drugs from the market and a frequent reason for the failure of drug
      candidates in the pre-clinical or clinical phases of drug development. This paper
      presents an approach for identifying potential liver toxicity genomic biomarkers
      from a liver toxicity biomarker study involving the paired compounds entacapone
      ("non-liver toxic drug") and tolcapone ("hepatotoxic drug"). Molecular analysis
      of the rat liver and plasma samples, combined with statistical analysis, revealed
      many similarities and differences between the in vivo biochemical effects of the
      two drugs. Six hundred and ninety-five genes and 61 pathways were selected based
      on the classification scheme. Of the 61 pathways, 5 were specific to treatment
      with tolcapone. Two of the 12 animals in the tolcapone group were found to have
      high ALT, AST, or TBIL levels. The gene Vars2 (valyl-tRNA synthetase 2) was
      identified in both animals and the pathway to which it belongs, the aminoacyl
      tRNA biosynthesis pathway, was one of the three most significant tolcapone
      specific pathways identified.

PMID- 21845100
TI  - Acid-denatured Green Fluorescent Protein (GFP) as model substrate to study the
      chaperone activity of protein disulfide isomerase.
AB  - Green fluorescent protein (GFP) has been widely used in several molecular and
      cellular biology applications, since it is remarkably stable in vitro and in
      vivo. Interestingly, native GFP is resistant to the most common chemical
      denaturants; however, a low fluorescence signal has been observed after acid
      induced denaturation. Furthermore, this acid-denatured GFP has been used as
      substrate in studies of the folding activity of some bacterial chaperones and
      other chaperone-like molecules. Protein disulfide isomerase enzymes, a family of
      eukaryotic oxidoreductases that catalyze the oxidation and isomerization of
      disulfide bonds in nascent polypeptides, play a key role in protein folding and
      it could display chaperone activity. However, contrasting results have been
      reported using different proteins as model substrates. Here, we report the
      further application of GFP as a model substrate to study the chaperone activity
      of protein disulfide isomerase (PDI) enzymes. Since refolding of acid-denatured
      GFP can be easily and directly monitored, a simple micro-assay was used to study
      the effect of the molecular participants in protein refolding assisted by PDI.
      Additionally, the effect of a well-known inhibitor of PDI chaperone activity was
      also analyzed. Because of the diversity their functional activities, PDI enzymes
      are potentially interesting drug targets. Since PDI may be implicated in the
      protection of cells against ER stress, including cancer cells, inhibitors of PDI
      might be able to enhance the efficacy of cancer chemotherapy; furthermore, it has
      been demonstrated that blocking the reductive cleavage of disulfide bonds of
      proteins associated with the cell surface markedly reduces the infectivity of the
      human immunodeficiency virus. Although several high-throughput screening (HTS)
      assays to test PDI reductase activity have been described, we report here a novel
      and simple micro-assay to test the chaperone activity of PDI enzymes, which is
      amenable for HTS of PDI inhibitors.

PMID- 21845101
TI  - Enhanced chiral recognition by cyclodextrin dimers.
AB  - In this article we investigate the effect of multivalency in chiral recognition.
      To this end, we measured the host-guest interaction of a beta-cyclodextrin dimer
      with divalent chiral guests. We report the synthesis of carbohydrate-based water
      soluble chiral guests functionalized with two borneol, menthol, or
      isopinocampheol units in either (+) or (-) configuration. We determined the
      interaction of these divalent guests with a beta-cyclodextrin dimer using
      isothermal titration calorimetry. It was found that-in spite of a highly
      unfavorable conformation-the cyclodextrin dimer binds to guest dimers with an
      increased enantioselectivity, which clearly reflects the effect of multivalency.

PMID- 21845102
TI  - Chitosan interaction with iron from yoghurt using an in vitro digestive model:
      comparative study with plant dietary fibers.
AB  - The objective of this work was to investigate the interaction of chitosan with
      iron from yoghurt by an in vitro gastrointestinal tract model. Taking into
      account that chitosan is a polysaccharide included in fiber definition by Codex
      Alimentarius; chitosan behavior was studied and compared with different plant
      fiber (wheat, bamboo, apple, psyllium and inulin) behaviors, in the same in vitro
      conditions. Ferrous sulfate was added to yoghurts with each type of fiber. The
      gastric environment was simulated with HCl (pH 1.0-2.0). The duodenal environment
      was simulated with NaHCO(3) (pH 6.8-7.2) and a dialysis tubing cellulose
      membrane. Results showed that chitosan had the highest iron retention percentages
      (53.2% at 30 min; 56.8% at 60 min) interacting in a more pronounced manner with
      iron than the plant fibers used in this work.

PMID- 21845103
TI  - Sida rhomboidea. Roxb leaf extract down-regulates expression of PPARgamma2 and
      leptin genes in high fat diet fed C57BL/6J Mice and retards in vitro 3T3L1 pre
      adipocyte differentiation.
AB  - Sida rhomboidea. Roxb leaf extract (SRLE) is being used by the populace of North
      East India to alleviate symptoms of diabetes and obesity. We have previously
      reported its hypolipidemic and anti-diabetic properties. In this study, we report
      the effect of SRLE on (i) in vivo modulation of genes controlling high fat diet
      (HFD) induced obesity and (ii) in vitro 3T3L1 pre-adipocyte differentiation and
      leptin release. Supplementation with SRLE significantly prevented HFD induced
      increment in bodyweight, plasma lipids and leptin, visceral adiposity and
      adipocyte hypertrophy. Also, SRLE supplementation reduced food intake, down
      regulated PPARgamma2, SREBP1c, FAS and LEP expressions and up-regulated CPT-1 in
      epididymal adipose tissue compared to obese mice. In vitro adipogenesis of 3T3L1
      pre-adipocytes was significantly retarded in the presence of SRLE extract. Also
      decreased triglyceride accumulation, leptin release and glyceraldehyde-3
      Phosphate dehydrogenase activity along with higher glycerol release without
      significant alteration of viability of 3T3L1 pre-adipocytes, was recorded. Our
      findings suggest that prevention of HFD induced visceral adiposity is primarily
      by down regulation of PPARgamma2 and leptin gene expression coupled with
      attenuation of food intake in C57BL/6J mice. SRLE induced prevention of pre
      adipocytes differentiation, and leptin release further substantiated these
      findings and scientifically validates the potential application of SRLE as a
      therapeutic agent against obesity.

PMID- 21845104
TI  - Effect of freeze-drying on the antioxidant compounds and antioxidant activity of
      selected tropical fruits.
AB  - The effects of freeze-drying on antioxidant compounds and antioxidant activity of
      five tropical fruits, namely starfruit (Averrhoa carambola L.), mango (Mangifera
      indica L.), papaya (Carica papaya L.), muskmelon (Cucumis melo L.), and
      watermelon Citruluss lanatus (Thunb.) were investigated. Significant (p < 0.05)
      differences, for the amounts of total phenolic compounds (TPC), were found
      between the fresh and freeze-dried fruit samples, except muskmelon. There was no
      significant (p > 0.05) change, however, observed in the ascorbic acid content of
      the fresh and freeze-dried fruits. Similarly, freeze-drying did not exert any
      considerable effect on beta-carotene concentration of fruits, except for mango
      and watermelon, where significantly (p < 0.05) higher levels were detected in the
      fresh samples. The results of DPPH (2,2-diphenyl-1-picrylhydrazyl) radical
      scavenging and reducing power assays revealed that fresh samples of starfruit and
      mango had relatively higher antioxidant activity. In case of linoleic acid
      peroxidation inhibition measurement, a significant (p < 0.05) but random
      variation was recorded between the fresh and freeze-dried fruits. Overall, in
      comparison to beta-carotene and ascorbic acid, a good correlation was established
      between the result of TPC and antioxidant assays, indicating that phenolics might
      have been the dominant compounds contributing towards the antioxidant activity of
      the fruits tested.

PMID- 21845105
TI  - Vma8p-GFP fusions can be functionally incorporated into V-ATPase, suggesting
      structural flexibility at the top of V1.
AB  - The vacuolar ATPase (V-ATPase) complex of yeast (Saccharomyces cerevisiae) is
      comprised of two sectors, V(1) (catalytic) and V(O) (proton transfer). The
      hexameric (A(3)B(3)) cylinder of V(1) has a central cavity that must accommodate
      at least part of the rotary stalk of V-ATPase, a key component of which is
      subunit D (Vma8p). Recent electron microscopy (EM) data for the prokaryote V
      ATPase complex (Thermus thermophilus) suggest that subunit D penetrates deeply
      into the central cavity. The functional counterpart of subunit D in mitochondrial
      F(1)F(O)-ATP synthase, subunit gamma, occupies almost the entire length of the
      central cavity. To test whether the structure of yeast Vma8p mirrors that of
      subunit gamma, we probed the location of the C-terminus of Vma8p by attachment of
      a large protein adduct, green fluorescent protein (GFP). We found that truncated
      Vma8p proteins lacking up to 40 C-terminal residues fused to GFP can be
      incorporated into functional V-ATPase complexes, and are able to support cell
      growth under alkaline conditions. We conclude that large protein adducts can be
      accommodated at the top of the central cavity of V(1) without compromising V
      ATPase function, arguing for structural flexibility of the V(1) sector.

PMID- 21845106
TI  - Epigenetics: new questions on the response to hypoxia.
AB  - Reduction in oxygen levels below normal concentrations plays important roles in
      different normal and pathological conditions, such as development, tumorigenesis,
      chronic kidney disease and stroke. Organisms exposed to hypoxia trigger changes
      at both cellular and systemic levels to recover oxygen homeostasis. Most of these
      processes are mediated by Hypoxia Inducible Factors, HIFs, a family of
      transcription factors that directly induce the expression of several hundred
      genes in mammalian cells. Although different aspects of HIF regulation are well
      known, it is still unclear by which precise mechanism HIFs activate transcription
      of their target genes. Concomitantly, hypoxia provokes a dramatic decrease of
      general transcription that seems to rely in part on epigenetic changes through a
      poorly understood mechanism. In this review we discuss the current knowledge on
      chromatin changes involved in HIF dependent gene activation, as well as on other
      epigenetic changes, not necessarily linked to HIF that take place under hypoxic
      conditions.

PMID- 21845107
TI  - Microcystin-LR induces apoptosis via NF-kappaB/iNOS pathway in INS-1 cells.
AB  - Cyanobacterial toxins, especially the microcystins, are found in eutrophied
      waters throughout the world, and their potential to impact on human and animal
      health is a cause for concern. Microcystin-LR (MC-LR) is one of the common toxic
      microcystin congeners and occurs frequently in diverse water systems. Recent work
      suggested that apoptosis plays a major role in the toxic effects induced by MC-LR
      in hepatocytes. However, the roles of MC-LR in pancreatic beta cells have not
      been fully established. The aim of the present study was to assess possible in
      vitro effects of MC-LR on cell apoptosis in the rat insulinoma cell line, INS-1.
      Our results demonstrated that MC-LR promoted selectively activation of NF-kappaB
      (increasing nuclear p50/p65 translocation) and increased the mRNA and protein
      levels of induced nitric oxide synthase (iNOS). The chronic treatment with MC-LR
      stimulated nitric oxide (NO) production derived from iNOS and induced apoptosis
      in a dose dependent manner in INS-1 cells. Meanwhile, this effect was inhibited
      by the NF-kappaB inhibitor PDTC, which reversed the apoptosis induced by MC-LR.
      Our observations indicate that MC-LR induced cell apoptosis via an iNOS-dependent
      pathway. A well-known nuclear transcription factor, NF-kappaB, is activated and
      mediates intracellular nitric oxide synthesis. We suggest that the apoptosis
      induced by chronic MC-LR in vivo presents a possible cause of beta-cell
      dysfunction, as a key environmental factor in the development of diabetes
      mellitus.

PMID- 21845108
TI  - Antifungal activity of denture soft lining material modified by silver
      nanoparticles-a pilot study.
AB  - Soft liner materials in oral cavity environments are easily colonized both by
      fungi and dental plaque. These factors are the cause of mucosal infections. The
      microorganism that most frequently colonizes soft liner materials is Candida
      albicans. Colonization occurs on the surface of materials and within materials. A
      solution to this problem might involve modification of soft liner materials with
      silver nanoparticles (AgNPs). In this article, we present results showing the
      antifungal efficacy of silicone soft lining materials modified with AgNPs. The
      modification process was conducted by dissolving both material components (base
      and catalyst) in a colloidal solution of AgNPs and evaporating the solvent.
      Composites with various AgNP concentrations (10, 20, 40, 80, 120 and 200 ppm)
      were examined. The in vitro antifungal efficacy (AFE) of composite samples was
      16.3% to 52.5%.

PMID- 21845110
TI  - Imaging utilization for the staging of clinically localized prostate cancer.

PMID- 21845109
TI  - Molecular basis for chiral selection in RNA aminoacylation.
AB  - The chiral-selective aminoacylation of an RNA minihelix is a potential progenitor
      to modern tRNA-based protein synthesis using l-amino acids. This article
      describes the molecular basis for this chiral selection. The extended double
      helical form of an RNA minihelix with a CCA triplet (acceptor of an amino acid),
      an aminoacyl phosphate donor nucleotide (mimic of aminoacyl-AMP), and a bridging
      nucleotide facilitates chiral-selective aminoacylation. Energetically, the
      reaction is characterized by a downhill reaction wherein an amino acid migrates
      from a high-energy acyl phosphate linkage to a lower-energy carboxyl ester
      linkage. The reaction occurs under the restriction that the nucleophilic attack
      of O, from 3'-OH in the terminal CCA, to C, from C=O in the acyl phosphate
      linkage, must occur at a Burgi-Dunitz angle, which is defined as the O-C=O angle
      of approximately 105 degrees . The extended double helical form results in a
      steric hindrance at the side chain of the amino acid leading to chiral preference
      combined with cation coordinations in the amino acid and the phosphate oxygen.
      Such a system could have developed into the protein biosynthetic system with an
      exclusively chiral component (l-amino acids) via (proto) ribosomes.

PMID- 21845111
TI  - From the Editor's Desk.

PMID- 21845112
TI  - A congressional perspective on organ allocation.

PMID- 21845113
TI  - The organ allocation controversy: how did we arrive here?
AB  - The Department of Health and Human Services (HHS) recently issued a final
      regulation governing the Organ Procurement and Transplantation Network (OPTN)
      that directs the allocation of organs to the sickest patients first without
      regard to a host of medical, geographic, and social factors that members of the
      transplant community view as an essential part of a sound organ allocation
      policy.Current organ allocation mechanisms are based on policies that reflect a
      broad consensus of medical experts and provide equal consideration for both the
      needs of the sickest patients and the efficient use of organs. This system also
      reduces potential waste of organs by minimizing cold ischemic time, increases
      access to transplantation for patients in local communities, provides positive
      incentives for local citizens and medical professionals to support organ donation
      initiatives, and decreases the cost of organ transplantation.Representatives of
      the American Society of Transplant Surgeons have testified before Congress that
      "giving priority to the sickest patients first over broad geographic areas would
      be wasteful and dangerous, resulting in fewer patients transplanted, increased
      death rates, increased retransplantation due to poor organ function, and
      increased overall cost of transplantation." In response, Congress enacted a 1
      year moratorium on the implementation of the HHS rule and provided for a study of
      the current organ allocation policy and HHS regulation by The Institute of
      Medicine.

PMID- 21845114
TI  - Advances in lung transplantation.
AB  - Success in lung transplantation (LT) has been attributed to proper patient and
      donor selection, better preservation and surgical techniques, and experience in
      postoperative management. In 1995, we refined our perioperative management by
      implementing newer perioperative strategies with critical pathways and have
      reduced use of cardio-pulmonary bypass (CPB), thereby improving survival after
      LT. We compared survival, use of CPB, intubation, intensive care unit (ICU) stay,
      and hospital times between PRE (prior to 1995) and POST cohorts to analyze our
      changes in LT. The 1-and 3-year survival rates were 57% and 29% for PRE, and 86%
      and 62% for POST, p < 0.01. The intubation time and ICU and hospital length of
      stay were significantly reduced in the POST cohort. Also, the need for CPB was
      reduced by about 40% in the POST group.

PMID- 21845115
TI  - Evolution of a statewide organ donation, recovery and allocation program: "a
      louisiana perspective".
AB  - This article reviews the evolution, growth, and impact of a structured organ
      recovery program on transplantation in Louisiana and discusses the clinical,
      social, and financial factors that influence the acceptance of organ
      transplantation as a viable treatment option for organ failure which once led
      inexorably to death. The rising number of organ donations and the formulation of
      strategies to increase these numbers to meet the growing need are examined.
      Enactment and enforcement of state and federal legislation making organ donation
      and transplantation available and safer have led to advances in organ donation,
      procurement, informed consent, and organ preservation, a technology that makes
      the use of cadaveric organs possible and durable.

PMID- 21845116
TI  - Current advances in liver transplantation.
AB  - Advances in the medical and surgical management of patients undergoing liver
      transplantation have made transplantation the method of choice for dealing with
      end-stage liver disease. With the availability of anti-viral agents such as
      interferon and ribavirin, pre and post transplant treatment of hepatitis C, the
      most common indication for liver transplantation, is now possible. The use of
      high dose hepatitis B immune globulin (HBIG) and lamivudine has decreased the
      incidence and severity of recurrence of hepatitis B after liver transplantation.
      Multimodal therapy including chemoembolization for hepatocellular carcinoma has
      made liver transplantation a viable option for selected patients with primary
      liver cancer. The development of more potent immunosuppressive agents has
      dramatically decreased the incidence of acute rejection, while the search for a
      solution to the problem of chronic rejection continues. Alcoholic liver disease
      remains a challenge for transplant physicians and surgeons; however, careful
      patient selection results in a relatively low rate of recidivism.Surgical
      advances in liver transplantation have focused on eliminating associated
      morbidity and mortality as well as expanding the donor pool. Veno-venous bypass
      (VVB) and T-tube stenting, which were once considered essential techniques in
      liver transplantation, are now only rarely, if ever, necessary. Operative time,
      blood product usage, and time to extubation, as well as intensive care unit stay,
      have all been significantly reduced by elimination of VVB without associated
      morbidity. Elimination of T-tube usage has also effectively decreased morbidity.
      Donor expansion has become critical as the need for liver transplants exceeds
      donor availability. Use of marginal donors, including older donors, donors with
      up to 40% fat content, and donors with high pressor requirements, has proven to
      be a safe and effective means of increasing the donor pool. In-situ splitting of
      donors is the most promising technical advance in liver transplantation. This
      technique, along with living-related liver transplantation, is very important for
      providing donors to the pediatric population where donor availability is even
      more limited.

PMID- 21845118
TI  - From the Editor's Desk.

PMID- 21845117
TI  - Multicenter studies of Lamivudine for the treatment and prevention of hepatitis B
      after liver transplantation.
AB  - Hepatitis B is a serious liver disease that may require liver transplantation.
      Recurrence of the initial infection in the grafted liver occurs frequently, and
      this is a frequent case of death after transplantation. Treatment of recurrent
      infection with interferon has been ineffective, and the only therapy that has
      been shown to prevent infection is high dose hepatitis B immune globulin (HBIg),
      a material that is very expensive and in short supply. In this article the author
      reviews the experience with lamivudine, an orally available nucleoside analogue,
      as a means of preventing and treating recurrent hepatitis B after liver
      transplantation. The results in both areas look promising, and it is possible
      that lamivudine maintenance therapy may obviate the need for life-long use of
      HBIg after liver transplantation. This will undergo study over the next several
      years in a multicenter trial supported by the National Institutes of Health.

PMID- 21845119
TI  - Cancer Knowledge, Attitudes and Beliefs among African Americans.
AB  - Four hundred two residents of a disadvantaged African American community in New
      Orleans were surveyed to determine their knowledge, attitudes, and beliefs
      regarding cancer and cancer screening. The residents were interviewed in their
      homes by trained community members. Two hundred ninety members of the Ochsner
      Health Plan (OHP) were also surveyed and the results from both groups were
      compared. Both groups were health conscious and expressed a willingness to
      participate in cancer screening. Mean cancer knowledge scores were lower in the
      target population (4.95) when compared with the OHP group (5.84). Thirty-two
      percent of the target population could identify the 7 cancer warning signs versus
      47% of the OHP group. Similar percentages of women in both groups could identify
      risk factors for breast cancer, but a number of etiologic myths were prevalent in
      the African American community. Participants in the African American community
      had a more fatalistic view of cancer and were less trusting of the medical
      community. Cancer screening rates were similar for cervical and colorectal
      cancer, but a significantly higher percentage of women in the OHP group received
      regular mammograms, 83% versus 43% in the target population. Thirty-two percent
      of the target population and 75% of the OHP group stated they had received a
      digital rectal examination. Only 34% of the African American males had received a
      Prostate Specific Antigen test versus 46% in the OHP group. The results of the
      survey identify a number of barriers to cancer screening among the African
      American community and support the need for a culturally sensitive, community
      based cancer education program.

PMID- 21845120
TI  - A selective approach to regional lymphatics in melanoma.
AB  - The management of regional lymphatics in patients with melanoma has evolved over
      the past several decades from delayed lymphadenectomy, to elective resection, to
      the current approach which utilizes sentinel lymph node mapping to accomplish a
      selective approach to performing lymphadenectomy. Sentinel lymphatic mapping
      allows for an opportunity to demonstrate regional lymphatic disease prior to the
      development of lymphadenopathy. Complete resection of a nodal basin can be
      reserved for patients with documented disease in a sentinel node while patients
      with a negative sentinel node can avoid an unnecessary and potentially morbid
      surgery. The preliminary results of sentinel node mapping at Ochsner Medical
      Institutions reflect an outstanding ability to demonstrate the sentinel node in
      patients with trunk and extremity melanoma when radioactive colloid is used in
      combination with a vital blue dye. The results of sentinel node mapping in
      patients with head and neck melanoma have not been as reliable and require
      additional refinements of technique.

PMID- 21845121
TI  - The emergence of a dynamic intervention paradigm in heart failure.
AB  - Traditionally, the heart failure management model has focused on crisis
      intervention, which allows the disease syndrome to progress to a point that
      requires emergent care followed by a cycle of prolonged and repeated
      hospitalizations (such contacts between the patient and care providers occur at
      times when the heart failure syndrome has deteriorated dangerously, and are only
      concerned with resolving the immediate crisis). Over time this approach of
      emergent care results in a marked decline in the patient's quality of life and
      creates a "revolving door" effect with the combined use of emergency department
      and hospital inpatient resources. The alternative is to become proactive and
      optimize treatment before such emergencies arise. This model relies on effective
      continuous outpatient and home care to stabilize the chronic condition and avoid
      hospital admissions. These concepts have led to the development of a new model or
      paradigm of outpatient strategies that have resulted in the creation of
      specialized heart failure disease management centers. This article discusses the
      economic and epidemiological forces that are driving this shift in our treatment
      focus and evaluates strategies that strike an optimum balance between cost
      containment and quality.

PMID- 21845122
TI  - The Family Practitioner's Role in Newborn Delivery at Ochsner.
AB  - Family practice physicians have contributed significantly to the care of
      maternity patients nationwide, but since the 1970s the number of family practice
      physicians delivering babies has decreased at a steady pace. In rural areas
      especially, family physicians are often the sole providers of care. Without these
      rural doctors providing maternal care, the risk of poor maternal/infant outcome
      increases. In the 1990s, it was found that residents of family medicine who are
      taught obstetrics all or in part by other family practice doctors are more likely
      to provide this kind of care when they finish residency. With this information,
      the Residency Review Committee that oversees national residency guidelines added
      the requirement that in all family practice residencies at least one practitioner
      must provide maternity care in an ongoing basis. To meet this challenge the
      country's medical training institutions quickly had to find new ways to teach and
      provide coverage for family practitioners involved in newborn delivery. Ochsner
      has developed credentialling for staff family practitioners to provide this care.
      Staff family practitioners are involved in the prenatal care of pregnant patients
      and have the opportunity to supervise their residents during labor and delivery.
      With the assistance of the obstetrical staff the Family Practice Residents'
      experience has greatly increased, reaching nearly 70 deliveries in 1998 alone
      with projections of over 100 for 1999.

PMID- 21845124
TI  - From the Editor's Desk.

PMID- 21845123
TI  - AIDS - Associated Kaposi's Sarcoma: A Double Jeopardy.

PMID- 21845125
TI  - United in the fight, divided in victory; will we really be successful against big
      tobacco?

PMID- 21845126
TI  - Alton ochsner, MD, 1896-1981 anti-smoking pioneer.

PMID- 21845127
TI  - Carcinoma of the lung and tobacco smoking: a historical perspective.

PMID- 21845128
TI  - Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79
      collected cases and presentation of 7 personal cases.

PMID- 21845129
TI  - The alton ochsner award relating smoking and health.

PMID- 21845130
TI  - Tobacco smoke: chemical carcinogenesis and genetic lesions.
AB  - Lung cancer is the primary cause of cancer-related death in the United States and
      smoking is the major contributing factor. An amazing array of carcinogenic and
      precarcinogenic agents has been identified in cigarette smoke. This review
      addresses the mechanisms by which some of the predominant lung carcinogens
      mutagenize DNA and explores some of the pivotal genes that are both susceptible
      to mutagenesis and contribute to the process of tumorigenesis and carcinogenesis.
      In addition, genes, gene products, and genetic polymorphisms, which curtail the
      processes leading to carcinogenesis, are discussed. The availability of
      clinically serviceable methods for analysis of genetic changes that can
      contribute to lung cancer is imperative to the development of timely, accurate,
      and cost-effective diagnostic and prognostic tests.A more thorough understanding
      of the step-wise conversion of precarcinogens to carcinogens, binding of
      carcinogens to DNA, mutation of DNA, DNA repair, and cellular destruction of
      carcinogens should contribute to the design of drugs that can modify these
      processes. In addition, introduction of genes (such as the p53 tumor supressor
      gene) into susceptible lung cells may impede carcinogenesis. Early stage clinical
      trials for the treatment of lung cancer using this and other genes are presently
      underway.

PMID- 21845131
TI  - Facts to physicians from the alton ochsner center for the elimination of smoking.

PMID- 21845132
TI  - Smoking cessation: the importance of medical intervention.

PMID- 21845134
TI  - From the Editor's Desk.

PMID- 21845133
TI  - Pharmacologic intervention in habitual smoking.
AB  - The health risks associated with smoking justify efforts at cessation. Of the 50
      million smokers in the United States, about 20 million attempt to quit each year.
      Approximately 6% are successful. Nicotine, the addictive agent within tobacco
      smoke, acts to enhance the release of neurotransmitters in the pleasure
      reinforcing area of the brain. Nicotine replacement therapy has been successfully
      used to relieve patients' withdrawal symptoms when cessation has been attempted.
      Nicotine replacement is available as a gum, patch, inhaler, and nasal spray.
      Bupropion, an antidepressant, is the first non-nicotine drug approved for smoking
      cessation. It blocks the neuronal uptake of serotonin and norepinephrine.
      Bupropion, like nicotine replacement therapy, is twice as effective as a placebo
      in smoking cessation.

PMID- 21845135
TI  - Endovascular repair of abdominal aortic aneurysms.
AB  - Endovascular treatment of abdominal aortic aneurysms (AAAs) is an exciting new
      minimally invasive treatment option for patients with this disease. Ochsner
      Clinic has been the only institution in the Gulf South participating in FDA
      clinical trials of these investigational devices. Early results with endovascular
      AAA repair demonstrate a trend towards lower mortality and morbidity when
      compared with traditional open surgery. Length of stay has been reduced by two
      thirds with a marked reduction in postoperative pain and at-home convalescence.
      If the long-term data on efficacy and durability of these devices are good, most
      AAAs in the future will be treated with this minimally invasive technique.

PMID- 21845136
TI  - Cardiopulmonary Rehabilitation, Exercise Training, and Preventive Cardiology: An
      Overview of a Decade of Research at the Ochsner Heart and Vascular Institute:
      Presented in part at Grand Rounds, Research Series, Ochsner Medical Institutions,
      May 17, 1999.
AB  - A decade of research from the Ochsner Heart and Vascular Institute's
      cardiopulmonary rehabilitation and exercise training programs demonstrates the
      benefits of this therapy on coronary risk factors, exercise capacity,
      cardiopulmonary parameters, behavioral characteristics, and quality of life in
      various subgroups of patients, including the elderly, women, obese patients, and
      groups with dyslipidemia and psychological distress, as well as in patients with
      congestive heart failure or severe lung disease. Substantial data from our
      program support the idea that cardiopulmonary rehabilitation and exercise
      training programs are underemphasized and underutilized for the secondary
      prevention of coronary artery disease.

PMID- 21845137
TI  - Practical considerations in the measurement of outcomes in healthcare.
AB  - In the current era of accountability in medicine, information regarding outcomes
      of care can play a pivotal role in medical decision making for physicians, other
      healthcare providers, patients, and administrators. Although the field of
      outcomes assessment has not fully matured, a number of tools and methods can be
      reliably used to produce valid information. Systematic collection and analysis of
      outcomes data can add to the complexity of the medical encounter. Yet, if
      appropriately collected, the information derived can facilitate medical decision
      making and enhance the quality of medical care. This article defines and
      discusses healthcare outcomes, reviews the relevance of outcomes measurement,
      describes practical considerations in, and examples of, outcomes measurement in
      medical practice, and reviews some resources available for outcomes studies or
      projects.

PMID- 21845138
TI  - Selective Outpatient Management of Upper Gastrointestinal Bleeding in the
      Elderly: Results from the SOME Bleeding Study.
AB  - To determine whether elderly patients with upper gastrointestinal bleeding could
      be safely managed as outpatients, 84 patients (65 years and older) were studied
      over a 23-month period. Urgent outpatient endoscopy was performed and clinical as
      well as endoscopic criteria were applied to determine the need for hospital
      admission. Patients with endoscopic findings that indicated a low risk for
      rebleeding were not admitted if they lacked one major or three minor predefined
      clinical criteria. All enrollees were monitored with hematocrit determination and
      clinical assessments for 4 weeks after discharge from the clinic or hospital.
      Twenty-four (29%) patients were treated as outpatients; none rebled. In contrast,
      seven (12%) of the 60 inpatients had one or more rebleeding episodes (p = 0.002).
      Bleeding from peptic ulcer disease was associated with use of nonsteroidal anti
      inflammatory medications in 81% of patients. We conclude that selective
      outpatient management of elderly patients with upper gastrointestinal bleeding
      can be done safely and can potentially reduce health care expenditures.

PMID- 21845139
TI  - The healthy start renal clinic: benefits of tracking and early intervention in
      pre-end stage renal disease patients.
AB  - Several studies have demonstrated a strong association between the benefits of
      pre-end stage renal disease (ESRD) education and decreased length of hospital
      stay (LOS) and hospital charges, delay of renal replacement therapy (RRT), and a
      smooth transition to RRT. The Ochsner Healthy Start Renal Clinic (HSRC) is a
      multidisciplinary early education and tracking program for pre-ESRD patients and
      their families. We identified and educated pre-ESRD patients about kidney
      disease, allowing them to discuss and make informed decisions about their
      treatment and be better prepared to cope with the transition to RRT and the
      changes in their lives resulting from kidney failure. HSRC patients demonstrated
      a significant decrease in length of hospital stay (p = 0.05), a trend towards
      decreased hospital episodes and charges, decreased use of temporary venous
      access, and a smooth transition to RRT. The control group was made up of patients
      who had either refused the structured education or had been referred to HSRC late
      and received only conventional instruction by a social worker at the point where
      dialysis was imminent. We compared the number of episodes of hospitalization,
      LOS, and overall hospital charges for the period immediately surrounding
      initiation of chronic dialysis (2 months before and 1 month following onset) of
      all 36 patients who began chronic hemodialysis in our facility between November
      1997 and November 1998. HSRC patients had LOS half as long (p=0.05), fewer
      hospital episodes, and hospital charges of $5,000 less per patient than the non
      HSRC group. Initial data strongly suggest that early education and intervention
      through the coordination of a multidisciplinary team maximize the continuity of
      patient care.

PMID- 21845140
TI  - Genetic instability in cancer: caretaker and gatekeeper genes.

PMID- 21845141
TI  - Is exercise stress testing a cost-saving strategy for risk assessment of
      pediatric wolff-Parkinson-white syndrome patients?
AB  - BACKGROUND: In Wolff-Parkinson-White syndrome (WPW) patients the loss of pre
      excitation in a single heartbeat during exercise stress testing (EST) is a
      predictor of low risk of sudden death. The purpose of this study was to: 1)
      assess the frequency of loss of pre-excitation in a single heartbeat during
      exercise testing, and 2) compare the cost of EST versus trans-catheter
      electrophysiology study (EPS) in the risk assessment of WPW patients. METHODS: A
      retrospective review of 50 cases of patients with WPW who underwent EST was
      conducted including demographics, history of supraventricular tachycardia,
      associated congenital heart disease, maximum heart rate achieved, and loss of pre
      excitation in a single heartbeat. Hospital costs of EST and EPS were compared.
      RESULTS: Of the 50 patients who underwent EST, 4 (8%), lost pre-excitation in a
      single heartbeat during EST. No differences were found regarding gender, age at
      diagnosis or EST, history of supraventricular tachycardia, presence of congenital
      heart disease or maximal heart rate. A cost comparison, utilizing the cost data:
      EST ($62.75) and EPS ($5,597) found EST to be a cost-saving approach in WPW
      patients. With 4 patients losing pre-excitation during EST, the cost saving of
      EST was $22,388 for this population of WPW patients. CONCLUSIONS: A frequency of
      8% loss of pre-excitation was found in a pediatric sample that underwent EST.
      Additionally, EST was shown to be a cost-saving strategy in risk assessment of
      pediatric WPW patients.

PMID- 21845142
TI  - Less-healthy eating behaviors have a greater association with a high level of
      sugar-sweetened beverage consumption among rural adults than among urban adults.
AB  - BACKGROUND: Sugar-sweetened beverage (SSB) consumption is associated with the
      increasing prevalence of overweight and obesity in the United States; however,
      little is known about how less-healthy eating behaviors influence high levels of
      SSB consumption among rural adults. OBJECTIVE: We assessed the frequency of SSB
      consumption among rural and urban adults, examined the correlates of frequent SSB
      consumption, and determined difference in correlates between rural and urban
      adults in a large region of Texas. DESIGN: A cross-sectional study using data on
      1,878 adult participants (urban=734 and rural=1,144), who were recruited by
      random digit dialing to participate in the seven-county 2006 Brazos Valley
      Community Health Assessment. Data included demographic characteristics, eating
      behaviors (SSB consumption, frequency of fast-food meals, frequency of breakfast
      meals, and daily fruit and vegetable intake), and household food insecurity.
      RESULTS: The prevalence of any consumption of SSB and the prevalence of high
      consumption of SSB were significantly higher among rural adults compared with
      urban counterparts. The multivariable logistic regression models indicated that a
      high level of SSB consumption (>=3 cans or glasses SSB/day) was associated with
      demographic characteristics (poverty-level income and children in the home),
      frequent consumption of fast-food meals, infrequent breakfast meals, low fruit
      and vegetable intake, and household food insecurity especially among rural
      adults. CONCLUSIONS: This study provides impetus for understanding associations
      among multiple eating behaviors, especially among economically and geographically
      disadvantaged adults. New strategies are needed for educating consumers, not only
      about how to moderate their SSB intake, but also how to simultaneously disrupt
      the co-occurrence of undesirable eating and promote healthful eating.

PMID- 21845143
TI  - Oral misoprostol for preventing postpartum haemorrhage in home births in rural
      Bangladesh: how effective is it?
AB  - AIMS: Evidence exists about prevention of postpartum haemorrhage (PPH) by oral
      administration of misoprostol in low-income countries, but effectiveness of
      prevention by lay community health workers (CHW) is not sufficient. This study
      aimed to investigate whether a single dose (400 ug) of oral misoprostol could
      prevent PPH in a community home-birth setting and to assess its acceptability and
      feasibility among rural Bangladeshi women. METHODS: This quasi-experimental trial
      was conducted among 2,017 rural women who had home deliveries between November
      2009 and February 2010 in two rural districts of northern Bangladesh. In the
      intervention district 1,009 women received 400 ug of misoprostol immediately
      after giving birth by the lay CHWs, and in the control district 1,008 women were
      followed after giving birth with no specific intervention against PPH. Primary
      PPH (within 24 hours) was measured by women's self-reported subjective measures
      of the normality of blood loss using the 'cultural consensus model.' Baseline
      data provided socio-economic, reproductive, obstetric, and bleeding disorder
      information. FINDINGS: The incidence of primary PPH was found to be lower in the
      intervention group (1.6%) than the control group (6.2%) (p<0.001). Misoprostol
      provided 81% protection (RR: 0.19; 95% CI: 0.08-0.48) against developing primary
      PPH. The proportion of retained and manually removed placentae was found to be
      higher in the control group compared to the intervention group. Women in the
      control group were more likely to need an emergency referral to a higher level
      facility and blood transfusion than the intervention group. Unexpectedly few
      women experienced transient side effects of misoprostol. Eighty-seven percent of
      the women were willing to use the drug in future pregnancy and would recommend to
      other pregnant women. CONCLUSION: Community-based distribution of oral
      misoprostol (400 ug) by CHW appeared to be effective, safe, acceptable, and
      feasible in reducing the incidence of PPH in rural areas of Bangladesh. This
      strategy should be scaled up across the country where access to skilled
      attendance is limited.

PMID- 21845144
TI  - Profiles and outcome of traditional healing practices for severe mental illnesses
      in two districts of Eastern Uganda.
AB  - BACKGROUND: The WHO estimates that more than 80% of African populations attend
      traditional healers for health reasons and that 40%-60% of these have some kind
      of mental illness. However, little is known about the profiles and outcome of
      this traditional approach to treatment. OBJECTIVE: The purpose of this study was
      to describe the profiles and outcome of traditional healing practices for severe
      mental illnesses in Jinja and Iganga districts in the Busoga region of Eastern
      Uganda. METHODS: Four studies were conducted. Study I used focus group
      discussions (FGDs) with case vignettes with local community members and
      traditional healers to explore the lay concepts of psychosis. Studies II and III
      concerned a cross-sectional survey of patients above 18 years at the traditional
      healer's shrines and study IV was made on a prospective cohort of patients
      diagnosed with psychosis in study III. Manual content analysis was used in study
      I; quantitative data in studies II, III, and IV were analyzed at univariate,
      bivariate, and multivariate levels to determine the association between
      psychological distress and socio-demographic factors; for study IV, factors
      associated with outcome were analyzed. One-way ANOVA for independent samples was
      the analysis used in Study IV. RESULTS: The community gave indigenous names to
      psychoses (mania, schizophrenia, and psychotic depression) and had multiple
      explanatory models for them. Thus multiple solutions for these problems were
      sought. Of the 387 respondents, the prevalence of psychological distress was
      65.1%, where 60.2% had diagnosable current mental illness, and 16.3% had had one
      disorder in their lifetime. Over 80% of patients with psychosis used both
      biomedical and traditional healing systems. Those who combined these two systems
      seemed to have a better outcome. All the symptom scales showed a percentage
      reduction of more than 20% at the 3- and 6-month follow-ups. CONCLUSION:
      Traditional healers shoulder a large burden of care of patients with mental
      health problems. This calls for all those who share the goal of improving the
      mental health of individuals to engage with traditional healers.

PMID- 21845145
TI  - Traditional healers for mental health care in Africa.

PMID- 21845146
TI  - Pulsed ultraviolet light reduces immunoglobulin E binding to Atlantic white
      shrimp (Litopenaeus setiferus) extract.
AB  - Pulsed ultraviolet light (PUV), a novel food processing and preservation
      technology, has been shown to reduce allergen levels in peanut and soybean
      samples. In this study, the efficacy of using PUV to reduce the reactivity of the
      major shrimp allergen, tropomyosin (36-kDa), and to attenuate immunoglobulin E
      (IgE) binding to shrimp extract was examined. Atlantic white shrimp (Litopenaeus
      setiferus) extract was treated with PUV (3 pulses/s, 10 cm from light source) for
      4 min. Tropomyosin was compared in the untreated, boiled, PUV-treated and
      [boiled+PUV]-treated samples, and changes in the tropomyosin levels were
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). IgE binding of the treated extract was analyzed via immunoblot and enzyme
      linked immunosorbent assay (ELISA) using pooled human plasma containing IgE
      antibodies against shrimp allergens. Results showed that levels of tropomyosin
      and IgE binding were reduced following PUV treatment. However, boiling increased
      IgE binding, while PUV treatment could offset the increased allergen reactivity
      caused by boiling. In conclusion, PUV treatment reduced the reactivity of the
      major shrimp allergen, tropomyosin, and decreased the IgE binding capacity of the
      shrimp extract.

PMID- 21845147
TI  - Anthropometric characteristics of hospitalised elderly women: a case-control
      study.
AB  - This study assessed the anthropometric status of 451 hospitalised female patients
      aged 70 or over, at their admission to hospital, in reference to 77 healthy women
      of the same age. The most frequent diseases were circulatory diseases (40.8%),
      mental disorders (29.9%), respiratory diseases (12.4%), endocrine and metabolic
      diseases (11.5%), osteomuscular diseases (8.4%), and traumatisms (6.9%). The
      differences were significantly high for mid-arm circumference (MAC), triceps
      skinfold thickness (TSF), weight, weight/height, and body mass index (BMI). The
      patients with cancers, blood diseases, mental disorders, respiratory disease,
      digestive diseases, or traumatisms had the lowest values. All the indicators
      correlated in a similarly negative way with age. The decreased TSF was more
      pronounced among subjects with respiratory diseases. Measurement of
      anthropometric indicators, TSF in particular, should be part of preventive
      measures aimed at reducing malnutrition and its consequences in a hospital
      setting.

PMID- 21845149
TI  - Prevalence of alcohol use and associated factors in urban hospital outpatients in
      South Africa.
AB  - The aim of this study was to assess the prevalence of alcohol use and associated
      factors among outpatients in an urban hospital in South Africa. The sample
      included 1,532 (56.4% men and women 43.6%) consecutively selected patients from
      different hospital outpatient departments. Results indicate that 41.2% of men and
      18.3% of women were found to be hazardous drinkers, and 3.6% of men and 1.4% of
      women meet criteria for probable alcohol dependence or harmful drinking as
      defined by the Alcohol Use Disorder Identification Test (AUDIT). Two in five
      patients (40.5%) were hazardous or harmful drinkers and/or had anxiety or
      depression. Logistic multiple regression found that for men tobacco use and not
      having been diagnosed with diabetes and for women tobacco use and having been
      diagnosed with migraine headache was associated with hazardous and harmful
      drinking. Although the study is cross-sectional, it does identify groups that may
      be at high risk of alcohol misuse and for whom intervention is urgent. Because
      prevalence of hazardous and harmful alcohol use is high in this population,
      routine screening should be introduced in hospital out-patient settings.

PMID- 21845150
TI  - Geotechnical characterization of mined clay from Appalachian Ohio: challenges and
      implications for the clay mining industry.
AB  - Clayey soil found in coal mines in Appalachian Ohio is often sold to landfills
      for constructing Recompacted Soil Liners (RSL) in landfills. Since clayey soils
      possess low hydraulic conductivity, the suitability of mined clay for RSL in Ohio
      is first assessed by determining its clay content. When soil samples are tested
      in a laboratory, the same engineering properties are typically expected for the
      soils originated from the same source, provided that the testing techniques
      applied are standard, but mined clay from Appalachian Ohio has shown drastic
      differences in particle size distribution depending on the sampling and/or
      laboratory processing methods. Sometimes more than a 10 percent decrease in the
      clay content is observed in the samples collected at the stockpiles, compared to
      those collected through reverse circulation drilling. This discrepancy poses a
      challenge to geotechnical engineers who work on the prequalification process of
      RSL material as it can result in misleading estimates of the hydraulic
      conductivity of the samples. This paper describes a laboratory investigation
      conducted on mined clay from Appalachian Ohio to determine how and why the
      standard sampling and/or processing methods can affect the grain-size
      distributions. The variation in the clay content was determined to be due to
      heavy concentrations of shale fragments in the clayey soils. It was also
      concluded that, in order to obtain reliable grain size distributions from the
      samples collected at a stockpile of mined clay, the material needs to be
      processed using a soil grinder. Otherwise, the samples should be collected
      through drilling.

PMID- 21845148
TI  - The protean toxicities of lead: new chapters in a familiar story.
AB  - Many times in the history of lead toxicology the view that "the problem" has been
      solved and is no longer a major health concern has prevailed, only to have
      further research demonstrate the prematurity of this judgment. In the last
      decade, an extraordinary amount of new research on lead has illustrated, all too
      clearly, that "the problem" has not disappeared, and that, in fact, it has
      dimensions never before considered. Recent risk assessments have concluded that
      research has yet to identify a threshold level below which lead can be considered
      "safe." Although children's intelligence has traditionally been considered to be
      the most sensitive endpoint, and used as the basis for risk assessment and
      standard setting, increased lead exposure has been associated with a wide variety
      of other morbidities both in children and adults, in some cases at biomarker
      levels comparable to those associated with IQ deficits in children. In adults,
      these endpoints include all-cause mortality and dysfunctions in the renal,
      cardiovascular, reproductive, central nervous systems. In children, IQ deficits
      are observed at blood lead levels well below 10 MUg/dL, and the dose-effect
      relationship appears to be supra-linear. Other health endpoints associated with
      greater early-life lead exposure in children include ADHD, conduct disorder,
      aggression and delinquency, impaired dental health, and delayed sexual
      maturation. Studies employing neuroimaging modalities such as volumetric,
      diffusion tensor, and functional MRI are providing insights into the neural bases
      of the cognitive impairments associated with greater lead exposure.

PMID- 21845151
TI  - Anabolic androgenic steroids--use and correlates among gym users--an assessment
      study using questionnaires and observations at gyms in the Stockholm region.
AB  - The purpose of this study was to estimate the prevalence of anabolic androgenic
      steroid (AAS) use and offers to use among gym users in Stockholm County (Sweden),
      and to conduct a comparison of concordance in estimates of AAS and supplements at
      gyms between two data collection methods. A questionnaire was distributed to
      members at 36 training facilities and 1,752 gym users participated in the study.
      An observation study was conducted as covert participant observations at 64 gyms.
      According to the questionnaire, 3.9% of men reported life time use of AAS, 1.4%
      use during the past 12 months and 0.4% AAS use during past 30 days. Not only were
      there similar patterns found in the two methods, i.e., similar age and gender
      distributions for AAS use, but analyses of concordance showed that gyms with a
      higher prevalence of self-reported AAS-use and supplement use (questionnaire)
      showed a significantly higher proportion of observer-assessed AAS users. Analyses
      of individual predictors showed that AAS users were almost always young men,
      regular weight trainers and more often users of drugs and nutritional
      supplements. The higher prevalence of AAS use among gym users than in the general
      population makes the former an appropriate target group for AAS prevention. The
      connection between supplements, drugs and AAS use suggests that effective AAS
      prevention need to focus on several risk factors for AAS use. The clear
      resemblance in estimates between the observation and questionnaire data
      strengthen the credibility of the two methods.

PMID- 21845152
TI  - Polycyclic aromatic hydrocarbon (PAH) exposure and DNA adduct semi-quantitation
      in archived human tissues.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic
      materials, mixtures of which contain multiple known and probable human
      carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled
      meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and
      topical absorption, and subsequently formed metabolites are either rendered
      hydrophilic and excreted, or bioactivated and bound to cellular macromolecules.
      The formation of PAH-DNA adducts (DNA binding products), considered a necessary
      step in PAH-initiated carcinogenesis, has been widely studied in experimental
      models and has been documented in human tissues. This review describes
      immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts
      in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated
      Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts
      concentrate in: basal and supra-basal epithelium of the esophagus, cervix and
      vulva; glandular epithelium of the prostate; and cytotrophoblast cells and
      syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the
      ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA
      adduct accumulation in specific, vulnerable, cell types. This semi-quantative
      method for PAH-DNA adduct measurement could potentially see widespread use in
      molecular epidemiology studies.

PMID- 21845153
TI  - Work and high-risk alcohol consumption in the Canadian workforce.
AB  - This study examined the associations between occupational groups; work
      organization conditions based on task design; demands, social relations, and
      gratifications; and weekly high-risk alcohol consumption among Canadian workers.
      A secondary data analysis was performed on Cycle 2.1 of the Canadian Community
      Health Survey conducted by Statistics Canada in 2003. The sample consisted of
      76,136 employees 15 years of age and older nested in 2,451 neighbourhoods. High
      risk alcohol consumption is defined in accordance with Canadian guidelines for
      weekly low-risk alcohol consumption. The prevalence of weekly high-risk alcohol
      consumption is estimated to be 8.1% among workers. The results obtained using
      multilevel logistic regression analysis suggest that increased work hours and job
      insecurity are associated with elevated odds of high-risk alcohol consumption.
      Gender female, older age, being in couple and living with children associated
      with lower odds of high-risk drinking, while increased education, smoking,
      physical activities, and, and economic status were associated with higher odds.
      High-risk drinking varied between neighbourhoods, and gender moderates the
      contribution of physical demands. The results suggest that work made a limited
      contribution and non-work factors a greater contribution to weekly high-risk
      alcohol consumption. Limits and implications of these results are discussed.

PMID- 21845154
TI  - Identification of candidate genes and physiological pathways involved in gonad
      deformation in whitefish (Coregonus spp.) from Lake Thun, Switzerland.
AB  - In 2000, fishermen reported the appearance of deformed reproductive organs in
      whitefish (Coregonus spp.) from Lake Thun, Switzerland. Despite intensive
      investigations, the causes of these abnormalities remain unknown. Using gene
      expression profiling, we sought to identify candidate genes and physiological
      processes possibly associated with the observed gonadal deformations, in order to
      gain insights into potential causes. Using in situ-synthesized oligonucleotide
      arrays, we compared the expression levels at 21,492 unique transcript probes in
      liver and head kidney tissue of male whitefish with deformed and normally
      developed gonads, respectively. The fish had been collected on spawning sites of
      two genetically distinct whitefish forms of Lake Thun. We contrasted the gene
      expression profiles of 56 individuals, i.e., 14 individuals of each phenotype and
      of each population. Gene-by-gene analysis revealed weak expression differences
      between normal and deformed fish, and only one gene, ictacalcin, was found to be
      up-regulated in head kidney tissue of deformed fish from both whitefish forms,
      However, this difference could not be confirmed with quantitative real-time qPCR.
      Enrichment analysis on the level of physiological processes revealed (i) the
      involvement of immune response genes in both tissues, particularly those linked
      to complement activation in the liver, (ii) proteolysis in the liver and (iii)
      GTPase activity and Ras protein signal transduction in the head kidney. In
      comparison with current literature, this gene expression pattern signals a
      chronic autoimmune disease in the testes. Based on the recent observations that
      gonad deformations are induced through feeding of zooplankton from Lake Thun we
      hypothesize that a xenobiotic accumulated in whitefish via the plankton
      triggering autoimmunity as the likely cause of gonad deformations. We propose
      several experimental strategies to verify or reject this hypothesis.

PMID- 21845155
TI  - Nationwide desert highway assessment: a case study in China.
AB  - The natural environment affects the construction of desert highways. Conversely,
      highway construction affects the natural environment and puts the ecological
      environment at a disadvantage. To satisfy the variety and hierarchy of desert
      highway construction and discover the spatio-temporal distribution of the natural
      environment and its effect on highway construction engineering, an assessment of
      the natural regional divisions of desert highways in China is carried out for the
      first time. Based on the general principles and method for the natural region
      division, the principles, method and index system for desert highway assessment
      is put forward by combining the desert highway construction features and the
      azonal differentiation law. The index system combines the dominant indicator and
      four auxiliary indicators. The dominant indicator is defined by the desert's
      comprehensive state index and the auxiliary indicators include the sand dune
      height, the blown sand strength, the vegetation coverage ratio and the annual
      average temperature difference. First the region is divided according to the
      dominant indicator. Then the region boundaries are amended according to the four
      auxiliary indicators. Finally the natural region division map for desert highway
      assessment is presented. The Chinese desert highways can be divided into three
      sections: the east medium effect region, the middle medium-severe effect region,
      and the west slight-medium effect region. The natural region division map
      effectively paves the way for the route planning, design, construction,
      maintenance and ongoing management of desert highways, and further helps
      environmental protection.

PMID- 21845156
TI  - Genetic risk for alcoholic chronic pancreatitis.
AB  - In recent years many studies have examined the genetic predisposition to
      pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined
      to be a multi-factorial disease, where environmental factors interact with the
      genetic profile of the individual. In this review we discuss the main results
      from studies examining the frequency of genetic mutations in alcoholic chronic
      pancreatitis.

PMID- 21845157
TI  - High tobacco use among lesbian, gay, and bisexual populations in West Virginian
      bars and community festivals.
AB  - With no information on tobacco use for lesbian, gay, or bisexual (LGB)
      populations in West Virginia (WV), it is unclear if nationally-identified LGB
      tobacco disparities also exist in this State. To address this data gap, we
      conducted a community tobacco survey in bars and events associated with the WV
      Pride Parade and Festival. Trained community surveyors used electronic and paper
      survey instruments in bars (n = 6) in three WV cities and community events
      associated with the WV Pride Parade and Festival. We analyzed results from 386
      completed surveys from self-identified LGB individuals. Tobacco use among LGB bar
      patrons and LGB attendees at Pride-affiliated events was elevated (45%), as was
      current cigarette use (41%). Users of cigars and chewing tobacco were frequently
      dual users of cigarettes, with 80% and 60% reporting dual use, respectively. A
      substantial disparity likely exists in tobacco use among LGB West Virginians.
      Targeted interventions addressing tobacco use among LGB West Virginians are
      warranted in these venues, and the addition of a demographic question on sexual
      orientation would improve data collection and monitoring of this disparity.

PMID- 21845159
TI  - Using geographically weighted regression (GWR) to explore spatial varying
      relationships of immature mosquitoes and human densities with the incidence of
      dengue.
AB  - The only way for dengue to spread in the human population is through the human
      mosquito-human cycle. Most research in this field discusses the dengue-mosquito
      or dengue-human relationships over a particular study area, but few have explored
      the local spatial variations of dengue-mosquito and dengue-human relationships
      within a study area. This study examined whether spatial heterogeneity exists in
      these relationships. We used Ordinary Least Squares (OLS) and Geographically
      Weighted Regression (GWR) models to analyze spatial relationships and identify
      the geographical heterogeneities by using the information of entomology and
      dengue cases in the cities of Kaohsiung and Fengshan in 2002. Our findings
      indicate that dengue-mosquito and dengue-human relationships were significantly
      spatially non-stationary. This means that in some areas higher dengue incidences
      were associated with higher vector/host densities, but in some areas higher
      incidences were related to lower vector/host densities. We demonstrated that a
      GWR model can be used to geographically differentiate the relationships of dengue
      incidence with immature mosquito and human densities. This study provides more
      insights into spatial targeting of intervention and control programs against
      dengue outbreaks within the study areas.

PMID- 21845158
TI  - The search for reliable biomarkers of disease in multiple chemical sensitivity
      and other environmental intolerances.
AB  - Whilst facing a worldwide fast increase of food and environmental allergies, the
      medical community is also confronted with another inhomogeneous group of
      environment-associated disabling conditions, including multiple chemical
      sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric
      hypersensitivity, amalgam disease and others. These share the features of poly
      symptomatic multi-organ cutaneous and systemic manifestations, with postulated
      inherited/acquired impaired metabolism of chemical/physical/nutritional
      xenobiotics, triggering adverse reactions at exposure levels far below
      toxicologically-relevant values, often in the absence of clear-cut allergologic
      and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms
      generating measurable disease biomarkers, these environmental hypersensitivities
      are generally ignored by sanitary and social systems, as psychogenic or
      "medically unexplained symptoms". The uncontrolled application of diagnostic and
      treatment protocols not corresponding to acceptable levels of validation, safety,
      and clinical efficacy, to a steadily increasing number of patients demanding
      assistance, occurs in many countries in the absence of evidence-based guidelines.
      Here we revise available information supporting the organic nature of these
      clinical conditions. Following intense research on gene polymorphisms of phase
      I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic
      and metabolic factors are under investigation, in particular free
      radical/antioxidant homeostasis disturbances. The finding of relevant alterations
      of catalase, glutathione-transferase and peroxidase detoxifying activities
      significantly correlating with clinical manifestations of MCS, has recently
      registered some progress towards the identification of reliable biomarkers of
      disease onset, progression, and treatment outcomes.

PMID- 21845160
TI  - Long-term gamma-hydroxybutyric acid (GHB) and disulfiram combination therapy in
      GHB treatment-resistant chronic alcoholics.
AB  - Leading Italian studies support the use of gamma-hydroxybutyric acid (GHB), not
      only in the treatment of the alcohol withdrawal syndrome, but also in maintaining
      alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in
      maintaining abstinence, and it has a better effect on craving than placebo or
      disulfiram. The problem is that about 30-40% of alcoholics are non-responders to
      GHB therapy. In our clinical practice, we speculate that by combining disulfiram
      with GHB treatment we may be able to achieve a kind of 'antagonist' effect by
      using the 'psychological threat' of disulfiram (adversative effect) while taking
      advantage of the anticraving effect of GHB, despite the limitation of its 'non
      blockade' effect on alcohol. In this context, to improve the outcome in GHB long
      term treated alcoholics, we added disulfiram to GHB in the management of GHB
      treatment-resistant alcoholics. In this study we compared retention in treatment
      of 52 patients who were treated with the GHB-disulfiram combination for up to six
      months, with retention for the same subjects considering their most recent
      unsuccessful outpatient long-term treatment with GHB only. An additional
      comparison was carried out on the days of complete abstention from alcohol.
      Thirty four patients (65.4%) successfully completed the protocol and were
      considered to be responders; 18 (34.6%) left the programme, and were considered
      to be non-responders. Considering the days of complete abstinence from alcohol,
      36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12
      stayed for a shorter time and four for the same time. The results of this study
      seem to indicate a higher efficacy of the GHB-disulfiram association compared
      with GHB alone. Randomized controlled trials are now needed to verify this
      hypothesis.

PMID- 21845161
TI  - Assessing environmental risks for established invasive weeds: Dalmatian (Linaria
      dalmatica) and yellow (L. vulgaris) toadflax in North America.
AB  - Environmental risk assessments characterizing potential environmental impacts of
      exotic weeds are more abundant and comprehensive for potential or new invaders
      than for widespread and well-established species such as Dalmatian (Linaria
      dalmatica [L.] Mill.) and yellow (L. vulgaris Mill.) toadflax. Specific effects
      evaluated in our assessment of environmental risks posed by yellow and Dalmatian
      toadflax included competitive displacement of other plant species, reservoirs of
      plant disease, animal and insect use, animal toxicity, human toxicity and
      allergenicity, erosion, and wildfire. Effect and exposure uncertainties for
      potential impacts of toadflax on human and ecological receptors were rated. Using
      publicly available information we were able to characterize ecological and human
      health impacts associated with toadflax, and to identify specific data gaps
      contributing to a high uncertainty of risk. Evidence supporting perceived
      negative environmental impacts of invasive toadflax was scarce.

PMID- 21845162
TI  - A review of frameworks for developing environmental health indicators for climate
      change and health.
AB  - The role climate change may play in altering human health, particularly in the
      emergence and spread of diseases, is an evolving area of research. It is
      important to understand this relationship because it will compound the already
      significant burden of diseases on national economies and public health.
      Authorities need to be able to assess, anticipate, and monitor human health
      vulnerability to climate change, in order to plan for, or implement action to
      avoid these eventualities. Environmental health indicators (EHIs) provide a tool
      to assess, monitor, and quantify human health vulnerability, to aid in the design
      and targeting of interventions, and measure the effectiveness of climate change
      adaptation and mitigation activities. Our aim was to identify the most suitable
      framework for developing EHIs to measure and monitor the impacts of climate
      change on human health and inform the development of interventions. Using
      published literature we reviewed the attributes of 11 frameworks. We identified
      the Driving force-Pressure-State-Exposure-Effect-Action (DPSEEA) framework as the
      most suitable one for developing EHIs for climate change and health. We propose
      the use of EHIs as a valuable tool to assess, quantify, and monitor human health
      vulnerability, design and target interventions, and measure the effectiveness of
      climate change adaptation and mitigation activities. In this paper, we lay the
      groundwork for the future development of EHIs as a multidisciplinary approach to
      link existing environmental and epidemiological data and networks. Analysis of
      such data will contribute to an enhanced understanding of the relationship
      between climate change and human health.

PMID- 21845165
TI  - Assessment of vulnerability to extreme flash floods in design storms.
AB  - There has been an increase in the occurrence of sudden local flooding of great
      volume and short duration caused by heavy or excessive rainfall intensity over a
      small area, which presents the greatest potential danger threat to the natural
      environment, human life, public health and property, etc. Such flash floods have
      rapid runoff and debris flow that rises quickly with little or no advance warning
      to prevent flood damage. This study develops a flash flood index through the
      average of the same scale relative severity factors quantifying characteristics
      of hydrographs generated from a rainfall-runoff model for the long-term observed
      rainfall data in a small ungauged study basin, and presents regression equations
      between rainfall characteristics and the flash flood index. The aim of this study
      is to develop flash flood index-duration-frequency relation curves by combining
      the rainfall intensity-duration-frequency relation and the flash flood index from
      probability rainfall data in order to evaluate vulnerability to extreme flash
      floods in design storms. This study is an initial effort to quantify the flash
      flood severity of design storms for both existing and planned flood control
      facilities to cope with residual flood risks due to extreme flash floods that
      have ocurred frequently in recent years.

PMID- 21845164
TI  - Alcohol consumption and oxidative DNA damage.
AB  - To examine the effects of alcohol consumption on cancer risk, we measured
      oxidative DNA damage and its repair activity in the livers and esophagi of rats
      fed with ethanol. Using our previously designed protocol for feeding rats with a
      high concentration of ethanol, we examined the effects of ethanol consumption on
      8-oxo-Gua generation and repair activity in the livers and esophagi of rats. We
      found that a high concentration of ethanol accompanied with a vitamin-depleted
      diet increased 8-oxo-Gua and its repair activity. 8-Oxo-Gua is known to induce
      point mutations, leading to carcinogenesis. Therefore, these results suggested
      that a high concentration of ethanol and an irregular diet increased liver and
      esophageal cancer risk. On the other hand, we showed that a low concentration of
      ethanol decreased 8-oxo-Gua and its repair activity in the livers of mice treated
      with a carcinogen. Taken together, the effects of ethanol consumption on cancer
      risk depend on the ethanol concentration and the diet pattern.

PMID- 21845163
TI  - Hypothalamic glial-to-neuronal signaling during puberty: influence of alcohol.
AB  - Mammalian puberty requires complex interactions between glial and neuronal
      regulatory systems within the hypothalamus that results in the timely increase in
      the secretion of luteinizing hormone releasing hormone (LHRH). Assessing the
      molecules required for the development of coordinated communication networks
      between glia and LHRH neuron terminals in the basal hypothalamus, as well as
      identifying substances capable of affecting cell-cell communication are
      important. One such pathway involves growth factors of the epidermal growth
      factor (EGF) family that bind to specific erbB receptors. Activation of this
      receptor results in the release of prostaglandin-E(2) (PGE(2)) from adjacent
      glial cells, which then acts on the nearby LHRH nerve terminals to elicit release
      of the peptide. Another pathway involves novel genes which synthesize
      adhesion/signaling proteins responsible for the structural integrity of bi
      directional glial-neuronal communication. In this review, we will discuss the
      influence of these glial-neuronal communication pathways on the prepubertal LHRH
      secretory system, and furthermore, discuss the actions and interactions of
      alcohol on these two signaling processes.

PMID- 21845166
TI  - Change of exposure response over time and long-term risk of silicosis among a
      cohort of Chinese pottery workers.
AB  - An analysis was conducted on a cohort of Chinese pottery workers to estimate the
      exposure-response relationship between respirable crystalline silica dust
      exposure and the incidence of radiographically diagnosed silicosis, and to
      estimate the long-term risk of developing silicosis until the age of 65. The
      cohort comprised 3,250 employees with a median follow-up duration of around 37
      years. Incident cases of silicosis were identified via silicosis registries
      (Chinese X-ray stage I, similar to International Labor Organisation
      classification scheme profusion category 1/1). Individual exposure to respirable
      crystalline silica dust was estimated based on over 100,000 historical dust
      measurements. The association between dust exposure, incidence and long-time risk
      of silicosis was quantified by Poisson regression analysis adjusted for age and
      smoking. The risk of silicosis depended not only on the cumulative respirable
      crystalline silica dust exposures, but also on the time-dependent respirable
      crystalline silica dust exposure pattern (long-term average concentration,
      highest annual concentration ever experienced and time since first exposure). A
      long-term "excess" risk of silicosis of approximately 1.5/1,000 was estimated
      among workers with all annual respirable crystalline silica dust concentration
      estimates less than 0.1 mg/m(3), using the German measurement strategy. This
      study indicates the importance of proper consideration of exposure information in
      risk quantification in epidemiological studies.

PMID- 21845167
TI  - Assessment of the interactions between economic growth and industrial wastewater
      discharges using co-integration analysis: a case study for China's Hunan
      Province.
AB  - We have investigated the interactions between economic growth and industrial
      wastewater discharge from 1978 to 2007 in China's Hunan Province using co
      integration theory and an error-correction model. Two main economic growth
      indicators and four representative industrial wastewater pollutants were selected
      to demonstrate the interaction mechanism. We found a long-term equilibrium
      relationship between economic growth and the discharge of industrial pollutants
      in wastewater between 1978 and 2007 in Hunan Province. The error-correction
      mechanism prevented the variable expansion for long-term relationship at quantity
      and scale, and the size of the error-correction parameters reflected short-term
      adjustments that deviate from the long-term equilibrium. When economic growth
      changes within a short term, the discharge of pollutants will constrain growth
      because the values of the parameters in the short-term equation are smaller than
      those in the long-term co-integrated regression equation, indicating that a
      remarkable long-term influence of economic growth on the discharge of industrial
      wastewater pollutants and that increasing pollutant discharge constrained
      economic growth. Economic growth is the main driving factor that affects the
      discharge of industrial wastewater pollutants in Hunan Province. On the other
      hand, the discharge constrains economic growth by producing external pressure on
      growth, although this feedback mechanism has a lag effect. Economic growth plays
      an important role in explaining the predicted decomposition of the variance in
      the discharge of industrial wastewater pollutants, but this discharge contributes
      less to predictions of the variations in economic growth.

PMID- 21845168
TI  - Seasonal variation of water quality and phytoplankton response patterns in Daya
      Bay, China.
AB  - Data collected from 12 stations in Daya Bay in different seasons in 2002 revealed
      the relation between water quality and phytoplankton response patterns. The
      results showed that Daya Bay could be divided into wet and dry seasons by
      multivariate statistical analysis. Principal component analysis indicated that
      temperature, chlorophyll a and nutrients were important components during the wet
      season (summer and autumn). The salinity and dissolved oxygen were the main
      environmental factors in the dry season (winter and spring). According to non
      metric multidimensional scaling, there was a shift from the large diatoms in the
      dry season to the smaller line-chain taxa in the wet season with the condition of
      a high dissolved inorganic nitrogen and nitrogen to phosphorous concentration
      ratio. Nutrient changes can thus alter the phytoplankton community composition
      and biomass, especially near the aquaculture farm areas. There was no evidence of
      an effect of thermal water from the nearby nuclear power plants on the observed
      changes in phytoplankton community and biomass in 2002.

PMID- 21845169
TI  - The environmental and social influences of HIV/AIDS in sub-Saharan Africa: a
      focus on rural communities.
AB  - The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS)
      pandemic has caused far-reaching effects in sub-Saharan Africa. The pandemic has
      effectively diminished the workforce, increased poverty rates, reduced
      agricultural productivity, and transformed the structure of many rural
      households. HIV/AIDS further strains the already fragile relationship between
      livelihood and the natural and social environments of these regions. Therefore,
      the objective of this review is to characterize the impact of HIV/AIDS on the
      environment and the social infrastructure of rural sub-Saharan Africa. There are
      many aspects of rural life that contribute to disease transmission of HIV/AIDS
      and that pose unique challenges to the population dynamics in sub-Saharan Africa.
      Widespread AIDS-related mortality has caused a decrease in population growth for
      many African countries. In turn, these alterations in population dynamics have
      resulted in a decrease in the percentage of prime-age working adults, as well as
      a gender disparity, whereby, females carry a growing burden of household
      responsibilities. There is a rising proportion of older adults, often females,
      who assume the role of provider and caretaker for other dependent family members.
      These changing dynamics have caused many to exploit their natural surroundings,
      adopting less sustainable land use practices and utilizing protected resources as
      a primary means of generating revenue.

PMID- 21845172
TI  - Global scenarios of air pollutant emissions from road transport through to 2050.
AB  - This paper presents global scenarios of sulphur dioxide (SO(2)), nitrogen oxides
      (NO(x)), and particulate matter (PM) emissions from road transport through to
      2050, taking into account the potential impacts of: (1) the timing of air
      pollutant emission regulation implementation in developing countries; (2) global
      CO(2) mitigation policy implementation; and (3) vehicle cost assumptions, on
      study results. This is done by using a global energy system model treating the
      transport sector in detail. The major conclusions are the following. First, as
      long as non-developed countries adopt the same vehicle emission standards as in
      developed countries within a 30-year lag, global emissions of SO(2), NO(x), and
      PM from road vehicles decrease substantially over time. Second, light-duty
      vehicles and heavy-duty trucks make a large and increasing contribution to future
      global emissions of SO(2), NO(x), and PM from road vehicles. Third, the timing of
      air pollutant emission regulation implementation in developing countries has a
      large impact on future global emissions of SO(2), NO(x), and PM from road
      vehicles, whereas there is a possibility that global CO(2) mitigation policy
      implementation has a comparatively small impact on them.

PMID- 21845171
TI  - Beneficial effects of ethanol consumption on insulin resistance are only
      applicable to subjects without obesity or insulin resistance; drinking is not
      necessarily a remedy for metabolic syndrome.
AB  - Although moderate drinking has been shown to lower insulin resistance levels, it
      is still unclear whether alcoholic beverages could be remedies for insulin
      resistance. To elucidate this, the correlation between levels of ethanol
      consumption and insulin resistance were cross-sectionally examined in 371 non
      diabetic male Japanese workers. Multiple regression analysis demonstrated that
      the ethanol consumption level was inversely correlated with the insulin
      resistance level assessed by homeostatic model assessment (HOMA-IR, p = 0.0014),
      the serum insulin level (p = 0.0007), and pancreatic beta-cell function, also
      assessed by HOMA (HOMA-beta, p = 0.0002), independently from age, body mass index
      (BMI), and blood pressure, liver function tests, and lipid profiles status, as
      well as serum adiponectin. The correlations were true in subjects with normal
      BMIs (up to 25.0 kg/m(2), n = 301) or normal HOMA-IR (up to 2.0 MUIU.mg/MUL.dL n
      = 337), whereas all of them were non-significant in those with excessive BMIs (n
      = 70) or in those with HOMA-IR of more than 2.0 (n = 34). Although it is still
      unclear whether the reductions of these parameters by ethanol consumption are
      truly due to the improvement of insulin resistance, at least, these effects are
      not applicable to subjects with obesity and/or insulin resistance. Thus,
      alcoholic beverages could not be remedies for insulin resistance or metabolic
      syndrome.

PMID- 21845173
TI  - Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe
      Magnus.
AB  - Repeated injection of opioid analgesics can lead to a progressive loss of effect.
      This phenomenon is known as tolerance. Several lines of investigations have shown
      that systemic, intraperitoneal administration or the microinjection of non-opioid
      analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain
      periaqueductal gray matter induces antinociception with some effects of
      tolerance. Our recent study has revealed that microinjection of three drugs
      analgin, ketorolac, and xefocam into the central nucleus of amygdala produce
      tolerance to them and cross-tolerance to morphine. Here we report that repeated
      administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the
      following 4 days result in progressively less antinociception compare to the
      saline control, i.e., tolerance develops to these drugs in male rats. Special
      control experiments showed that post-treatment with the MU-opioid antagonist
      naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs
      on the first day of testing in the tail-flick (TF) reflex and hot plate (HP)
      latency tests. On the second day, naloxone generally had trend effects in both TF
      and HP tests and impeded the development of tolerance to the antinociceptive
      effect of non-opioid analgesics. These findings strongly support the suggestion
      of endogenous opioid involvement in NSAIDs antinociception and tolerance in the
      descending pain-control system. Moreover, repeated injections of NSAIDs
      progressively lead to tolerance to them, cross-tolerance to morphine, and the
      risk of a withdrawal syndrome. Therefore, these results are important for human
      medicine too.

PMID- 21845170
TI  - Features of microglia and neuroinflammation relevant to environmental exposure
      and neurotoxicity.
AB  - Microglia are resident cells of the brain involved in regulatory processes
      critical for development, maintenance of the neural environment, injury and
      repair. They belong to the monocytic-macrophage lineage and serve as brain immune
      cells to orchestrate innate immune responses; however, they are distinct from
      other tissue macrophages due to their relatively quiescent phenotype and tight
      regulation by the CNS microenvironment. Microglia actively survey the surrounding
      parenchyma and respond rapidly to changes such that any disruption to neural
      architecture or function can contribute to the loss in regulation of the
      microglia phenotype. In many models of neurodegeneration and neurotoxicity, early
      events of synaptic degeneration and neuronal loss are accompanied by an
      inflammatory response including activation of microglia, perivascular monocytes,
      and recruitment of leukocytes. In culture, microglia have been shown to be
      capable of releasing several potentially cytotoxic substances, such as reactive
      oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives,
      excitatory amino acids, and cytokines; however, they also produce various
      neurotrophic factors and quench damage from free radicals and excitotoxins. As
      the primary source for pro-inflammatory cytokines, microglia are implicated as
      pivotal mediators of neuroinflammation and can induce or modulate a broad
      spectrum of cellular responses. Neuroinflammation should be considered as a
      balanced network of processes whereby subtle modifications can shift the cells
      toward disparate outcomes. For any evaluation of neuroinflammation and microglial
      responses, within the framework of neurotoxicity or degeneration, one key
      question in determining the consequence of neuroinflammation is whether the
      response is an initiating event or the consequence of tissue damage. As examples
      of environmental exposure-related neuroinflammation in the literature, we provide
      an evaluation of data on manganese and diesel exhaust particles.

PMID- 21845174
TI  - The role of insulin-like growth factor-I in the physiopathology of hearing.
AB  - Insulin-like growth factor-I (IGF-I) belongs to the family of polypeptides of
      insulin, which play a central role in embryonic development and adult nervous
      system homeostasis by endocrine, autocrine, and paracrine mechanisms. IGF-I is
      fundamental for the regulation of cochlear development, growth, and
      differentiation, and its mutations are associated with hearing loss in mice and
      men. Low levels of IGF-I have been shown to correlate with different human
      syndromes showing hearing loss and with presbyacusis. Animal models are
      fundamental to understand the genetic, epigenetic, and environmental factors that
      contribute to human hearing loss. In the mouse, IGF-I serum levels decrease with
      aging and there is a concomitant hearing loss and retinal degeneration. In the
      Igf1(-/-) null mouse, hearing loss is due to neuronal loss, poor innervation of
      the sensory hair cells, and age-related stria vascularis alterations. In the
      inner ear, IGF-I actions are mediated by intracellular signaling networks, RAF,
      AKT, and p38 MAPK protein kinases modulate the expression and activity of
      transcription factors, as AP1, MEF2, FoxM1, and FoxP3, leading to the regulation
      of cell cycle and metabolism. Therapy with rhIGF-I has been approved in humans
      for the treatment of poor linear growth and certain neurodegenerative diseases.
      This review will discuss these findings and their implications in new IGF-I-based
      treatments for the protection or repair of hearing loss.

PMID- 21845176
TI  - A novel elevated plus-maze procedure to avoid the one-trial tolerance problem.
AB  - The elevated plus-maze (EPM) test is one of the most commonly used behavioral
      assays to evaluate anxiety-related behavior in rodents. It is an economic test (5
      min duration) without prior conditioning of the animals. The critical measure for
      anxiety is the time spent in the open arms of the maze. A confounding problem of
      the EPM is the so called one-trial tolerance (OTT), characterized by a marked
      decrease of open arm exploration in spite of treatment with anxiolytic acting
      benzodiazepines upon re-exposure to the EPM. This consistent finding is often
      raised as an evidence for the inappropriateness to re-test rodents in the EPM.
      However, a reliable re-test paradigm would broaden the usability and
      effectiveness of this test. Therefore, we tested how an extension of the inter
      trial interval to 28 days (instead of the usual 24 h), and an additional change
      of the testing room would affect the open arm time and other behaviors on the
      EPM. In two experiments, drug-naive Wistar rats were exposed to the EPM on trial
      1, and treated intraperitoneally with either vehicle or midazolam (0.25 mg/kg) 30
      min before trial 2. Then, trial 2 (28 days after trial 1) was carried out in
      either the same testing room (Experiment 1) or in another unfamiliar room
      (Experiment 2). Twenty-eight days after trial 1 the open arm time of the rats in
      the vehicle treated control rats of both experimental groups was comparable to
      that of the first trial, independent of the testing room. Most importantly, we
      found that the treatment with the benzodiazepine midazolam had a significantly
      anxiolytic-like (i.e., increase of open arm time) effect in trial 2 only when
      conducted in the previously unfamiliar testing room (Experiment 2). We suggest
      that in order to reliably re-test the EPM and to prevent confounding effects due
      to the OTT, an inter-trial interval of 28 days and a change in testing rooms
      reinstates anxiolytic-like actions of benzodiazepines.

PMID- 21845175
TI  - Design of a neurally plausible model of fear learning.
AB  - A neurally oriented conceptual and computational model of fear conditioning
      manifested by freezing behavior (FRAT), which accounts for many aspects of delay
      and context conditioning, has been constructed. Conditioning and extinction are
      the result of neuromodulation-controlled LTP at synapses of thalamic, cortical,
      and hippocampal afferents on principal cells and inhibitory interneurons of
      lateral and basal amygdala. The phenomena accounted for by the model (and
      simulated by the computational version) include conditioning, secondary
      reinforcement, blocking, the immediate shock deficit, extinction, renewal, and a
      range of empirically valid effects of pre- and post-training ablation or
      inactivation of hippocampus or amygdala nuclei.

PMID- 21845177
TI  - Neural mechanisms of impaired fear inhibition in posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) can develop in some individuals who are
      exposed to an event that causes extreme fear, horror, or helplessness (APA,
      1994). PTSD is a complex and heterogeneous disorder, which is often co-morbid
      with depression, substance abuse, and anxiety disorders such as panic or social
      phobia. Given this complexity, progress in the field can be greatly enhanced by
      focusing on phenotypes that are more proximal to the neurobiology of the
      disorder. Such neurobiological intermediate phenotypes can provide investigative
      tools to increase our understanding of the roots of the disorder and develop
      better prevention or intervention programs. In the present paper, we argue that
      the inhibition of fear responses is an intermediate phenotype that is related to
      both the neurocircuitry associated with the disorder, and is linked to its
      clinical symptoms. An advantage of focusing on fear inhibition is that the
      neurobiology of fear has been well investigated in animal models providing the
      necessary groundwork in understanding alterations. Furthermore, because many
      paradigms can be tested across species, fear inhibition is an ideal translational
      tool. Here we review both the behavioral tests and measures of fear inhibition
      and the related neurocircuitry in neuroimaging studies with both healthy and
      clinical samples.

PMID- 21845178
TI  - Electrophysiological correlates of reading the single- and interactive-mind.
AB  - Understanding minds is the cognitive basis of successful social interaction. In
      everyday life, human mental activity often happens at the moment of social
      interaction among two or multiple persons instead of only one-person.
      Understanding the interactive mind of two- or multi-person is more complex and
      higher than understanding the single-person mind in the hierarchical structure of
      theory of mind. Understanding the interactive mind maybe differentiate from
      understanding the single mind. In order to examine the dissociative
      electrophysiological correlates of reading the single mind and reading the
      interactive mind, the 64 channels event-related potentials were recorded while 16
      normal adults were observing three kinds of Chinese idioms depicted physical
      scenes, one-person with mental activity, and two- or multi-person with mental
      interaction. After the equivalent N400, in the 500- to 700-ms epoch, the mean
      amplitudes of late positive component (LPC) over frontal for reading the single
      mind and reading the interactive mind were significantly more positive than for
      physical representation, while there was no difference between the former two. In
      the 700- to 800-ms epoch, the mean amplitudes of LPC over frontal-central for
      reading the interactive mind were more positive than for reading the single mind
      and physical representation, while there was no difference between the latter
      two. The present study provides electrophysiological signature of the
      dissociations between reading the single mind and reading the interactive mind.

PMID- 21845179
TI  - GenNet: A Platform for Hybrid Network Experiments.
AB  - We describe General Network (GenNet), a software plugin for the real time
      experimental interface (RTXI) dynamic clamp system that allows for
      straightforward and flexible implementation of hybrid network experiments. This
      extension to RTXI allows for hybrid networks that contain an arbitrary number of
      simulated and real neurons, significantly improving upon previous solutions that
      were limited, particularly by the number of cells supported. The benefits of this
      system include the ability to rapidly and easily set up and perform scalable
      experiments with hybrid networks and the ability to scan through ranges of
      parameters. We present instructions for installing, running and using GenNet for
      hybrid network experiments and provide several example uses of the system.

PMID- 21845180
TI  - Processing Semblances Induced through Inter-Postsynaptic Functional LINKs,
      Presumed Biological Parallels of K-Lines Proposed for Building Artificial
      Intelligence.
AB  - The internal sensation of memory, which is available only to the owner of an
      individual nervous system, is difficult to analyze for its basic elements of
      operation. We hypothesize that associative learning induces the formation of
      functional LINK between the postsynapses. During memory retrieval, the activation
      of either postsynapse re-activates the functional LINK evoking a semblance of
      sensory activity arriving at its opposite postsynapse, nature of which defines
      the basic unit of internal sensation - namely, the semblion. In neuronal networks
      that undergo continuous oscillatory activity at certain levels of their
      organization re-activation of functional LINKs is expected to induce semblions,
      enabling the system to continuously learn, self-organize, and demonstrate
      instantiation, features that can be utilized for developing artificial
      intelligence (AI). This paper also explains suitability of the inter-postsynaptic
      functional LINKs to meet the expectations of Minsky's K-lines, basic elements of
      a memory theory generated to develop AI and methods to replicate semblances
      outside the nervous system.

PMID- 21845181
TI  - Similar Structures but Different Roles - An Updated Perspective on TLR
      Structures.
AB  - Toll-like receptors (TLRs) are pattern recognition receptors that recognize
      conserved structures in pathogens, trigger innate immune responses, and prime
      antigen-specific adaptive immunity. Elucidation of crystal structures of TLRs
      interacting with their ligands such as TLR1-2 with triacylated lipopeptide, TLR2
      6 with diacylated lipopeptide, TLR4-MD-2 with LPS, and TLR3 with double-stranded
      RNA (dsRNA) have enabled an understanding of the initiation of TLR signaling.
      Agonistic ligands such as LPS, dsRNA, and lipopeptides induce "m" shaped TLR
      dimers in which C-termini converge at the center. Such central convergence is
      necessary to bring the two intracellular receptor TIR domains closer together and
      promote their dimerization, which serves as an essential step in downstream
      signaling. In this review, we summarize TLR ECD structures that have been
      reported to date with special emphasis on ligand recognition and activation
      mechanism.

PMID- 21845182
TI  - Architecture of explanatory inference in the human prefrontal cortex.
AB  - Causal reasoning is a ubiquitous feature of human cognition. We continuously seek
      to understand, at least implicitly and often explicitly, the causal scenarios in
      which we live, so that we may anticipate what will come next, plan a potential
      response and envision its outcome, decide among possible courses of action in
      light of their probable outcomes, make midstream adjustments in our goal-related
      activities as our situation changes, and so on. A considerable body of research
      shows that the lateral prefrontal cortex (PFC) is crucial for causal reasoning,
      but also that there are significant differences in the manner in which
      ventrolateral PFC, dorsolateral PFC, and anterolateral PFC support causal
      reasoning. We propose, on the basis of research on the evolution, architecture,
      and functional organization of the lateral PFC, a general framework for
      understanding its roles in the many and varied sorts of causal reasoning carried
      out by human beings. Specifically, the ventrolateral PFC supports the generation
      of basic causal explanations and inferences; dorsolateral PFC supports the
      evaluation of these scenarios in light of some given normative standard (e.g., of
      plausibility or correctness in light of real or imagined causal interventions);
      and anterolateral PFC supports explanation and inference at an even higher level
      of complexity, coordinating the processes of generation and evaluation with
      further cognitive processes, and especially with computations of hedonic value
      and emotional implications of possible behavioral scenarios - considerations that
      are often critical both for understanding situations causally and for deciding
      about our own courses of action.

PMID- 21845183
TI  - Facilitated auditory detection for speech sounds.
AB  - If it is well known that knowledge facilitates higher cognitive functions, such
      as visual and auditory word recognition, little is known about the influence of
      knowledge on detection, particularly in the auditory modality. Our study tested
      the influence of phonological and lexical knowledge on auditory detection. Words,
      pseudo-words, and complex non-phonological sounds, energetically matched as
      closely as possible, were presented at a range of presentation levels from sub
      threshold to clearly audible. The participants performed a detection task
      (Experiments 1 and 2) that was followed by a two alternative forced-choice
      recognition task in Experiment 2. The results of this second task in Experiment 2
      suggest a correct recognition of words in the absence of detection with a
      subjective threshold approach. In the detection task of both experiments,
      phonological stimuli (words and pseudo-words) were better detected than non
      phonological stimuli (complex sounds), presented close to the auditory threshold.
      This finding suggests an advantage of speech for signal detection. An additional
      advantage of words over pseudo-words was observed in Experiment 2, suggesting
      that lexical knowledge could also improve auditory detection when listeners had
      to recognize the stimulus in a subsequent task. Two simulations of detection
      performance performed on the sound signals confirmed that the advantage of speech
      over non-speech processing could not be attributed to energetic differences in
      the stimuli.

PMID- 21845184
TI  - Broad Themes of Difference between French and Americans in Attitudes to Food and
      Other Life Domains: Personal Versus Communal Values, Quantity Versus Quality, and
      Comforts Versus Joys.
AB  - Analysis of previous literature on the role of food in life in France and the
      United States suggests some fundamental differences in attitudes which may
      generalize outside of the food domain. Questionnaire results from French and
      American adults suggest that, compared to the French, Americans emphasize
      quantity rather than quality in making choices, Americans have a higher
      preference for variety, and Americans usually prefer comforts (things that make
      life easier) over joys (unique things that make life interesting). The American
      preference for quantity over quality is discussed in terms of the American focus
      on abundance as opposed to the French preference for moderation. The American
      preference for variety is reflective of Americans' more personal as opposed to
      communal food and other values.

PMID- 21845186
TI  - Monoclonal Antibodies Bind A SNP-Sensitive Epitope that is Present Uniquely in
      Mycobacterium avium Subspecies Paratuberculosis.
AB  - Due to a close genetic relatedness, there is no known antibody that detects
      Mycobacterium avium subspecies paratuberculosis (MAP), which causes Johne's
      disease in cattle and sheep, and does not cross-react with other M. avium
      subspecies. In the present study, a monoclonal antibody (MAb; 17A12) was
      identified from mice immunized with a cell membrane fraction of MAP strain K-10.
      This antibody is 100% specific as it detected a 25-kDa protein in all 29 MAP
      whole cell lysates, but did not bind to any of the 29 non-paratuberculosis
      strains tested in immunoblot assays. However, the antibody revealed variable
      reactivity levels in MAP strains as it detected higher levels in bovine isolates
      but comparably lower levels in ovine isolates of MAP. In order to identify the
      target binding protein for 17A12, a lambda phage expression library of MAP
      genomic fragments was screened with the MAb. Four reactive clones were
      identified, sequenced and all shown to be overlapping. Further analysis revealed
      all four clones expressed an unknown protein encoded by a sequence that is not
      annotated in the K-10 genome and overlapped with MAP3422c on the opposing DNA
      strand. The epitope of 17A12 was precisely defined to seven amino acids and was
      used to query the K-10 genome. Similarity searches revealed another protein,
      encoded by MAP1025, possessed a similar epitope (one-amino acid mismatch) that
      also reacted strongly to the antibody. A single nucleotide polymorphism (SNP) in
      MAP1025 was then identified by comparative sequence analysis, which results in a
      Pro28His change at residue 28, the first amino acid within the 17A12 epitope.
      This SNP is present in all MAP strains but absent in all non-MAP strains and
      accounts for the specificity of the 17A12 antibody. This new antibody is the
      first ever isolated that binds only to the paratuberculosis subspecies of M.
      avium and opens new possibilities for the specific detection of this significant
      ruminant pathogen.

PMID- 21845188
TI  - Degree and Predictors of Functional Loss of the Operated Kidney following Nephron
      Sparing Surgery: Assessment by Quantitative SPECT of 99m Tc-Dimercaptosuccinic
      Acid Scintigraphy.
AB  - Purpose. To determine the degree and predictors of renal function loss of the
      operated kidney following nephron-sparing surgery (NSS). Material and methods.
      The study group included 113 patients with renal mass who underwent NSS at our
      institution. QDMSA before and 3-6 months after surgery was used for evaluation
      differences in renal function of each kidney. Mean change of percent uptake by
      the kidney was correlated with various clinical and pathological variables.
      Results. The overall average decrease of renal function of the operated kidney as
      measured by QDMSA was 10.5% +/- 2.6 SER. Among the studied variables, the most
      important predictors of postoperative ipsilateral residual kidney function were
      estimated blood loss (EBL), P = 0.0003, duration of warm ischemia, P = 0.008,
      patient's age at surgery, P = 0.024, method used for tumor bed closure, P = 0.06,
      and location of the lesion, P = 0.08. Conclusions. Carful hemostasis, minimal
      duration of arterial clamping, and use of tissue adhesives to seal tumor bed are
      associated with maximal preservation of postoperative residual renal function
      after NSS. These variables should be considered by the operative team when
      planning the surgical procedure .

PMID- 21845187
TI  - Prevention of Post-ERCP Pancreatitis.
AB  - Pancreatitis is the most common complication of ERCP. It can be associated with
      substantial morbidity. Hence, the minimization of both the incidence and severity
      of post-ERCP pancreatitis is paramount. Considerable efforts have been made to
      identify factors that may be associated with an increased risk of this
      complication. In addition, both procedure- and pharmacological-related
      interventions have been proposed that may prevent this complication. This paper
      outlines these interventions and presents the evidence to support their use in
      the prevention of post-ERCP pancreatitis.

PMID- 21845185
TI  - Horizontal gene exchange in environmental microbiota.
AB  - Horizontal gene transfer (HGT) plays an important role in the evolution of life
      on the Earth. This view is supported by numerous occasions of HGT that are
      recorded in the genomes of all three domains of living organisms. HGT-mediated
      rapid evolution is especially noticeable among the Bacteria, which demonstrate
      formidable adaptability in the face of recent environmental changes imposed by
      human activities, such as the use of antibiotics, industrial contamination, and
      intensive agriculture. At the heart of the HGT-driven bacterial evolution and
      adaptation are highly sophisticated natural genetic engineering tools in the form
      of a variety of mobile genetic elements (MGEs). The main aim of this review is to
      give a brief account of the occurrence and diversity of MGEs in natural
      ecosystems and of the environmental factors that may affect MGE-mediated HGT.

PMID- 21845189
TI  - Clinical pharmacology of chemotherapy agents in older people with cancer.
AB  - Populations around the world are aging, and the associated increase in cancer
      incidence has led to the recognition of the importance of geriatric oncology.
      Chronological age is a poor determinant of pharmacological response to cancer
      chemotherapy agents. Age-associated changes in physiology and organ function have
      a significant impact on the clinical pharmacology of cancer chemotherapy agents
      used in cancer treatment. Altered response to medicines in older people is a
      consequence of changes in body composition, organ function, concomitant
      pathophysiology, multiple medications, genetic determinants of drug response, and
      patient's clinical status. These issues highlight the need to individualize the
      management of cancer in the older people with consideration of age-related
      changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive
      therapies.

PMID- 21845190
TI  - PU.1 and Haematopoietic Cell Fate: Dosage Matters.
AB  - The ETS family transcription factor PU.1 is a key regulator of haematopoietic
      differentiation. Its expression is dynamically controlled throughout
      haematopoiesis in order to direct appropriate lineage specification. Elucidating
      the biological role of PU.1 has proved challenging. This paper will discuss how a
      range of experiments in cell lines and mutant and transgenic mouse models have
      enhanced our knowledge of the mechanisms by which PU.1 drives lineage-specific
      differentiation during haematopoiesis.

PMID- 21845191
TI  - ATP-Sensitive Potassium Channel Currents in Eccentrically Hypertrophied Cardiac
      Myocytes of Volume-Overloaded Rats.
AB  - ATP-sensitive potassium channels (K(ATP)) protect the myocardium from hypertrophy
      induced by pressure-overloading. In this study, we determined the effects of
      these channels in volume-overloading. We compared the effects of a K(ATP) agonist
      and a K(ATP) antagonist on sarcolemmal transmembrane current density (pA/pF)
      clamped at 20 mV increments of membrane potential from -80 to +40 mV in
      ventricular cardiac myocytes. The basal outward potassium pA/pF in myocytes of
      volume-overloaded animals was significantly smaller than that in the myocytes of
      sham-operated controls. Treatment of the control myocytes with the K(ATP) agonist
      cromakalim increased pA/pF significantly. This increase was blocked by the K(ATP)
      antagonist glibenclamide. Treatment of the hypertrophied myocytes from volume
      overloaded animals with cromakalim and in the presence and absence of
      glibenclamide did not change pA/pF significantly. These findings suggest that
      eccentrically hypertrophied cardiac myocytes from volume-overloading may be
      unresponsive to specific activation/inactivation of K(ATP) and that dysfunctional
      K(ATP) may fail to protect the myocardium from left ventricular hypertrophy
      associated with volume-overloading.

PMID- 21845192
TI  - Parotid Gland Biopsy as an Additional Diagnostic Tool for Supporting the
      Diagnosis of Sjogren's Syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease characterized by
      keratoconjunctivitis sicca and xerostomia. There are actually no diagnostic
      criteria for SS, but classification criteria based on the revised American
      European criteria have been elaborated. These include subjective criteria: ocular
      and oral symptoms, and objective criteria: ocular, histopathological, oral, and
      serological signs. SS is considered if 4 of the 6 criteria are present, when
      histopathology or serology is positive, or if 3 of any 4 objective criteria are
      present. A patient presented with both ocular and oral symptoms and signs but did
      not meet the SS classification criteria. Indeed, no anti-SSA or anti-SSB
      antibodies were detected, and minor salivary gland biopsy was normal. To further
      understand the origin of the sicca symptoms, a parotid gland biopsy was performed
      and showed important lymphocytic infiltrates. This could account for the sicca
      symptoms and signs since parotid glands are one the major contributors to
      salivary flow. Therefore, parotid gland biopsy could be a useful asset for the
      diagnosis of SS.

PMID- 21845193
TI  - Fluid Retention over the Menstrual Cycle: 1-Year Data from the Prospective
      Ovulation Cohort.
AB  - We report menstrual and mid-cycle patterns of self-reported "fluid retention" in
      765 menstrual cycles in 62 healthy women. Self-reported "fluid retention,"
      commonly described as bloating, is one element of the clinical assessment and
      diagnosis of premenstrual symptoms. These daily diary data were collected as part
      of an observational prospective one-year study of bone changes in healthy women
      of differing exercise characteristics. Ovulation was documented by quantitative
      basal temperature analysis, and serum estradiol and progesterone levels were
      available from initial and final cycles. Fluid retention scores (on a 0-4 scale)
      peaked on the first day of menstrual flow (mean +/- SE : 0.9 +/- 0.1), were
      lowest during the mid-follicular period, and gradually increased from 0.22 +/-
      0.05 to 0.50 +/- 0.09 over the 11 days surrounding ovulation. Mid-cycle, but not
      premenstrual, fluid scores tended to be lower in anovulatory cycles (ANOVA P =
      0.065), and scores were higher around menstruation than at midcycle (P < 0.0001).
      Neither estradiol nor progesterone levels were significantly associated with
      fluid retention scores. The peak day of average fluid retention was the first day
      of flow. There were no significant differences in women's self-perceived fluid
      retention between ovulatory and anovulatory cycles.

PMID- 21845194
TI  - Normal coronary artery patient presenting with left ventricular aneurysm.
AB  - Left ventricular aneurysm (LVA) is one of the most important complications of
      myocardial infarction LVA is strictly defined as a distinct area of abnormal left
      ventricular diastolic contour with systolic dyskinesia or paradoxical bulging.
      LVA usually results from myocardial infarction. Other rare aetiologies of LVA
      include hypertrophic cardiomyopathy, Chagas' disease, sarcoidosis, congenital
      LVA, and idiopathic However, LVA formation in patients with idiopathic dilated
      cardiomyopathy is rarely reported, and the incidence, clinical features, and
      pathogenesis of LVA formation in patients with idiopathic dilated cardiomyopathy
      is not well understood. Here, we present a 45 years old, idiopathic dilated
      cardiomyopathy patient with LVA and normal coronary arteries The pathogenesis of
      LVA formation in patients with idiopathic dilated cardiomyopathy is not clear.
      One acceptable hypothesis is that coronary artery emboli originate from mural
      thrombi, present in some patients with idiopathic dilated cardiomyopathy, which
      develop due to local wall infarction and fibrosis. The local myocardial perfusion
      differences could be seen in idiopathic dilated cardiomyopathy and predominantly
      found in the anteroposterior axis of the left ventricle. Local fibrosis occurs
      more frequently on the anterior wall or posterior wall, and less frequently on
      the lateral or septal wall. In our patient, LVA existed in the septal segments.We
      could not define the exact mechanism of the septal aneurysm in our patient but we
      decided to present this abnormal case, which is different from cases thus far
      reported in the literature.

PMID- 21845196
TI  - Risk Factors and Seroprevalence of Hepatitis C among Patients Hospitalized at
      Mulago Hospital, Uganda.
AB  - The emergence of hepatitis C virus (HCV) and its associated sequelae in Africa is
      a cause for significant concern. Human immunodeficiency virus (HIV) positive
      patients are at an increased risk of contracting HCV infection due to similar
      risk factors and modes of transmission. We investigated the seroprevalence of
      hepatitis C in hospitalized HIV-positive and HIV-negative patients in Mulago
      Hospital, an academic hospital in Uganda. Blood samples were first tested for HCV
      antibodies, and positive tests were confirmed with HCV RNA PCR. We enrolled five
      hundred patients, half HIV-positive and half HIV negative. Overall, 13/500
      patients (2.6%) tested positive for HCV antibodies. There was no difference in
      HCV antibody detection among HIV-positive and HIV-negative patients. Out of all
      risk factors examined, only an age greater than 50 years was associated with HCV
      infection. Traditional risk factors for concurrent HIV and HCV transmission, such
      as intravenous drug use, were exceedingly rare in Uganda. Only 3 of 13 patients
      with detectable HCV antibodies were confirmed by HCV RNA detection. This result
      concurs with recent studies noting poor performance of HCV antibody testing when
      using African sera. These tests should be validated in the local population
      before implementation.

PMID- 21845195
TI  - In vitro differentiation and maturation of human embryonic stem cell into
      multipotent cells.
AB  - Human embryonic stem cells (hESCs), which have the potential to generate
      virtually any differentiated progeny, are an attractive cell source for
      transplantation therapy, regenerative medicine, and tissue engineering. To
      realize this potential, it is essential to be able to control ESC differentiation
      and to direct the development of these cells along specific pathways. Basic
      science in the field of embryonic development, stem cell differentiation, and
      tissue engineering has offered important insights into key pathways and scaffolds
      that regulate hESC differentiation, which have produced advances in modeling
      gastrulation in culture and in the efficient induction of endoderm, mesoderm,
      ectoderm, and many of their downstream derivatives. These findings have lead to
      identification of several pathways controlling the differentiation of hESCs into
      mesodermal derivatives such as myoblasts, mesenchymal cells, osteoblasts,
      chondrocytes, adipocytes, as well as hemangioblastic derivatives. The next
      challenge will be to demonstrate the functional utility of these cells, both in
      vitro and in preclinical models of bone and vascular diseases.

PMID- 21845197
TI  - Cytokine and Phenotypic Cell Profiles of Leishmania infantum Infection in the
      Dog.
AB  - Leishmaniasis has reemerged in recent years showing a wider geographic
      distribution and increased global incidence of human and canine disease than
      previously known. Dogs are the main domestic/peridomestic reservoir hosts of
      zoonotic visceral leishmaniasis caused by Leishmania infantum. Since the
      evolution of leishmaniasis and clinical appearance is a consequence of complex
      interactions between the parasite and host immune response, a profound knowledge
      about the immune profile developed in dog's infection is crucial for vaccine and
      immunomodulatory therapy design. The main goal of this paper is to compile the
      recent advances made on cytokine and phenotypic cell profiles in different
      tissues and organs of dogs infected with L. infantum. This paper also stressed
      that the knowledge of the immune responses developed, namely, in liver, lymph
      node, and spleen is very limited. All data emphasizes that more research on
      canine leishmaniasis is necessary for the development of new and efficacious
      tools to control zoonotic leishmaniasis.

PMID- 21845198
TI  - Use of ghrelin as a treatment for inflammatory bowel disease: mechanistic
      considerations.
AB  - Inflammatory bowel diseases (IBD)-and in particular Crohn's disease-are immune
      mediated processes that result in denuded intestinal mucosa and can produce
      decreased appetite, weight loss, and systemic inflammation. Current treatments
      include anti-inflammatory medications, immunomodulators, and feeding
      interventions. Ghrelin is an endogenous orexigenic hormone that directly
      stimulates growth hormone release, increases gut motility, and has cardiovascular
      and anti-inflammatory properties. Although ghrelin levels are elevated in active
      IBD, administration of ghrelin in most (but not all) animal models of colitis has
      produced improvements in disease activity and systemic inflammation. The
      mechanism for these effects is not known but may relate to decreased
      inflammation, increased motility, increased appetite, and increased colonic blood
      flow. Human trials have not been performed, however, and more research is clearly
      needed.

PMID- 21845199
TI  - Novel lipolytic enzymes identified from metagenomic library of deep-sea sediment.
AB  - Metagenomic library was constructed from a deep-sea sediment sample and screened
      for lipolytic activity. Open-reading frames of six positive clones showed only 33
      58% amino acid identities to the known proteins. One of them was assigned to a
      new group while others were grouped into Families I and V or EstD Family. By
      employing a combination of approaches such as removing the signal sequence,
      coexpression of chaperone genes, and low temperature induction, we obtained five
      soluble recombinant proteins in Escherichia coli. The purified enzymes had
      optimum temperatures of 30-35 degrees C and the cold-activity property. Among
      them, one enzyme showed lipase activity by preferentially hydrolyzing p
      nitrophenyl palmitate and p-nitrophenyl stearate and high salt resistance with up
      to 4 M NaCl. Our research demonstrates the feasibility of developing novel
      lipolytic enzymes from marine environments by the combination of functional
      metagenomic approach and protein expression technology.

PMID- 21845201
TI  - Changes of Photosynthetic Behaviors in Kappaphycus alvarezii Infected by
      Epiphyte.
AB  - Epiphytic filamentous algae (EFA) were noted as a serious problem to reduce the
      production and quality of K. alvarezii. The morphological studies revealed that
      the main epiphyte on K. alvarezii was Neosiphonia savatieri in China. Though the
      harmful effects of EFA on the production of K. alvarezii have been reported, the
      detailed mechanism of the N. savatieri in limiting the production of K. alvarezii
      has not been studied yet. The present paper studied the effects of N. savatieri
      infection on photosynthetic behaviors in K. alvarezii by detecting chlorophyll
      fluorescence transient in vivo. The results revealed that damage of oxygen
      evolving complex (OEC), decrease of active reaction centers (RCs), and the
      plastoquinone (PQ) pool as well as significant reduction in the performance
      indexes (PI) of PSII were caused by the infection of N. savatieri. The influence
      of N. savatieri on photosynthetic activity of K. alvarezii should be one of the
      important reasons to reduce the production of K. alvarezii infected by N.
      savatieri.

PMID- 21845200
TI  - Developing the effective method of spectral harmonic energy ratio to analyze the
      arterial pulse spectrum.
AB  - In this article, we analyze the arterial pulse in the spectral domain. A
      parameter, the spectral harmonic energy ratio (SHER), is developed to assess the
      features of the overly decreased spectral energy in the fourth to sixth harmonic
      for palpitation patients. Compared with normal subjects, the statistical results
      reveal that the mean value of SHER in the patient group (57.7 +/- 27.9) is
      significantly higher than that of the normal group (39.7 +/- 20.9) (P-value =
      .0066 < .01). This means that the total energy in the fourth to sixth harmonic of
      palpitation patients is significantly less than it is in normal subjects. In
      other words, the spectral distribution of the arterial pulse gradually decreases
      for normal subjects while it decreases abruptly in higher-order harmonics (the
      fourth, fifth and sixth harmonics) for palpitation patients. Hence, SHER is an
      effective method to distinguish the two groups in the spectral domain. Also, we
      can thus know that a "gradual decrease" might mean a "balanced" state, whereas an
      "abrupt decrease" might mean an "unbalanced" state in blood circulation and pulse
      diagnosis. By SHER, we can determine the ratio of energy distribution in
      different harmonic bands, and this method gives us a novel viewpoint from which
      to comprehend and quantify the spectral harmonic distribution of circulation
      information conveyed by the arterial pulse. These concepts can be further applied
      to improve the clinical diagnosis not only in Western medicine but also in
      traditional Chinese medicine (TCM).

PMID- 21845202
TI  - Comparative Cytogenetics Analysis of Chlamys farreri, Patinopecten yessoensis,
      and Argopecten irradians with Ct-1 DNA by Fluorescence In Situ Hybridization.
AB  - The chromosomes of Chlamys farreri, Patinopecten yessoensis, and Argopecten
      irradians were studied by FISH using C. farreri C(0)t-1 DNA probes. The results
      showed that C(0)t-1 DNA signals spread on all chromosomes in the three scallops,
      whereas signal density and intensity were different strikingly. Clustering
      brighter signals presented in the centromeric and telomeric regions of most C.
      farreri chromosomes, and in the centromeric or pericentromeric regions of several
      P. yessoensis chromosomes. Comparative analysis of the mapping indicated a
      relatively higher homology in the repetitive DNA sequences of the genome between
      C. farreri and P. yessoensis than that between C. farreri and A. irradians. In
      addition, FISH showed that the distribution of C(0)t-1 DNA clustering signals in
      C. farreri displayed completely similar signal bands between homologous
      chromosomes. Based on the C(0)t-1 DNA fluorescent bands, a more exact karyotype
      of C. farreri has been obtained. In this study, the comparative analysis based on
      C(0)t-1 DNA provides a new insight into the chromosomal reconstructions during
      the evolution process, and it is helpful for understanding an important source of
      genomic diversity, species relationships, and genome evolution.

PMID- 21845203
TI  - Enhanced Antitumoral Activity of Extracts Derived from Cultured Udotea flabellum
      (Chlorophyta).
AB  - Very few studies have been performed to evaluate the effect of culture conditions
      on the production or activity of active metabolites in algae. Previous studies
      suggest that the synthesis of bioactive compounds is strongly influenced by
      irradiance level. To investigate whether the antiproliferative activity of Udotea
      flabellum extracts is modified after cultivation, this green alga was cultured
      under four photon flux densities (PFD) for 30 days. After 10, 20, and 30 days,
      algae were extracted with dichloromethane: methanol and screened for
      antiproliferative activity against four human cancer cell lines (laryngeal-Hep-2,
      cervix-HeLa, cervix squamous-SiHa and nasopharynx-KB) by SRB assay. Lipid and
      phenol content were evaluated by standardized methods on algae organic extracts.
      After 10 days of cultivation, organic U. flabellum extracts showed a significant
      increase in antiproliferative activity on Hela and SiHa cells when compared to
      noncultured algae extracts. Extracts obtained after 10 and 20 days of culture
      were active on KB and Hep-2 cells. Total phenol and polyunsaturated fatty acid
      content in organic extracts changed with cultivation time but not by irradiance
      treatment. Extracts from U. flabellum obtained after 10 and 20 days of culture
      have been selected for fractionation and isolation of active compounds.

PMID- 21845204
TI  - Phytochemical characteristics, free radical scavenging activities, and
      neuroprotection of five medicinal plant extracts.
AB  - The objective of this study was to determine phytochemical characteristics,
      chemiluminescence antioxidant capacities, and neuroprotective effects on PC12
      cells for methanol extracts of Spatholobus suberectus, Uncaria rhynchophylla,
      Alpinia officinarum, Drynaria fortunei, and Crataegus pinnatifida. The C.
      pinnatifida extract (CPE) afforded the greatest yield and total phenolic content.
      The S. suberectus extract (SSE) yielded the greatest total flavonoid content. The
      U. rhynchophylla extract (URE) produced the greatest total tannin content, and
      the A. officinarum extract (AOE) produced the greatest total triterpenoid
      content. The D. fortunei extract, assayed using horseradish peroxidase-luminol
      hydrogen peroxide (H(2)O(2)), and AOE using pyrogallol-luminol assay each
      exhibited better antioxidant activity than the L-ascorbic acid and 6-hydroxy
      2,5,7,8-tetramethylchroman-2-carboxylic acid did. The CPE, SSE, and URE presented
      neurogrowth effects and neuroprotective activities on H(2)O(2)-induced PC12 cell
      death at 0.5-5.0 MUg/mL. The CPE represents a promising medicinal plant source
      for the treatment of H(2)O(2)-induced neurodegenerative disease, because of its
      useful phytochemical characteristics.

PMID- 21845205
TI  - Mechanisms in the adaptation of maternal beta-cells during pregnancy.
AB  - Pancreatic beta-cell mass adapts to changing insulin demands in the body. One of
      the most amazing reversible beta-cell adaptations occurs during pregnancy and
      postpartum conditions. During pregnancy, the increase in maternal insulin
      resistance is compensated by maternal beta-cell hyperplasia and
      hyperfunctionality to maintain normal blood glucose. Although the cellular
      mechanisms involved in maternal beta-cell expansion have been studied in detail
      in rodents, human studies are very sparse. A summary of these studies in rodents
      and humans is described below. Since beta-cell mass expands during pregnancy,
      unraveling the endocrine/paracrine/autocrine molecular mechanisms responsible for
      these effects can be of great importance for predicting and treating gestational
      diabetes and for finding new cues that induce beta-cell regeneration in diabetes.
      In addition to the well known implication of lactogens during maternal beta-cell
      expansion, additional participants are being discovered such as serotonin and
      HGF. Transcription factors, such as hepatocyte nuclear factor-4alpha and the
      forkhead box protein-M1, and cell cycle regulators, such as menin, p27 and p18,
      are important intracellular signals responsible for these effects. In this
      article, we summarize and discuss novel studies uncovering molecular mechanisms
      involved in the maternal beta-cell adaptive expansion during pregnancy.

PMID- 21845206
TI  - Near-atomic-resolution cryo-EM for molecular virology.
AB  - Electron cryo-microscopy (cryo-EM) is a technique in structural biology that is
      widely used to solve the three-dimensional structures of macromolecular
      assemblies, close to their biological and solution conditions. Recent
      improvements in cryo-EM and single-particle reconstruction methodologies have led
      to the determination of several virus structures at near-atomic resolution (3.3 -
      4.6 A). These cryo-EM structures not only resolve the Calpha backbones and side
      chain densities of viral capsid proteins, but also suggest functional roles that
      the protein domains and some key amino acid residues play. This paper reviews the
      recent advances in near-atomic-resolution cryo-EM for probing the mechanisms of
      virus assembly and morphogenesis.

PMID- 21845207
TI  - Partial high-resolution structure of phosphorylated and non-phosphorylated
      leucine-rich amelogenin protein adsorbed to hydroxyapatite.
AB  - The formation of biogenic materials requires the interaction of organic molecules
      with the mineral phase. In forming enamel, the amelogenin proteins contribute to
      the mineralization of hydroxyapatite (HAp). Leucine-rich amelogenin protein
      (LRAP) is a naturally occurring splice variant of amelogenin that comprises
      amelogenin's predicted HAp binding domains. We determined the partial structure
      of phosphorylated and non-phosphorylated LRAP variants bound to HAp using
      combined solid-state NMR (ssNMR) and ssNMR-biased computational structure
      prediction. New ssNMR measurements in the N-terminus indicate a largely extended
      structure for both variants, though some measurements are consistent with a
      partially helical N-terminal segment. The N-terminus of the phosphorylated
      variant is found to be consistently closer to the HAp surface than the non
      phosphorylated variant. Structure prediction was biased using 21 ssNMR
      measurements in the N- and C-terminus at five HAp crystal faces. The predicted
      fold of LRAP is similar at all HAp faces studied, regardless of phosphorylation.
      Largely consistent with experimental observations, LRAP's predicted structure is
      relatively extended with a helix-turn-helix motif in the N-terminal domain and
      some helix in the C-terminal domain, and the N-terminal domain of the
      phosphorylated variant binds HAp more closely than the N-terminal domain of the
      non-phosphorylated variant. Predictions for both variants show some potential
      binding specificity for the {010} HAp crystal face, providing further support
      that amelogenins block crystal growth on the a and b faces to allow elongated
      crystals in the c-axis.

PMID- 21845208
TI  - AIDS-Related Pathology.

PMID- 21845209
TI  - Disease Extent >=4 cm Is a Prognostic Marker of Local Recurrence in T1-2 Breast
      Cancer.
AB  - Despite improvements of the therapy for breast cancer, a proportion of the
      patients still get local recurrence. The status of the surgical margins is the
      most often used parameter for decision regarding additional treatment. However, a
      negative margin is not a guarantee that there is not residual cancer left in the
      breast; additional parameters are needed to better predict the risk of local
      recurrence. The disease extent was evaluated in the surgical specimen from 313
      women after breast-conserving therapy using large-section histology and was
      correlated to the incidence of local recurrence. A disease extent >=4 cm was
      shown to be an independent marker for local recurrence; the cumulative 10-year
      local relapse rate for the group with a disease extent >=4 cm was 20.5%, and for
      the rest 6.7%. We conclude that disease extent >=4 cm seems to be an important
      factor when evaluating the risk for local recurrence.

PMID- 21845210
TI  - Histopathological and genomic grading provide complementary prognostic
      information in breast cancer: a study on publicly available datasets.
AB  - The genomic grade (GG) for breast cancer is thought to be the genomic counterpart
      of histopathological grade (HG). The motivation behind this study was to see
      whether HG retains its prognostic impact even when adjusted for GG, or whether it
      can be replaced by the latter. Four publicly available gene expression datasets
      were analyzed. Kaplan-Meier curves, log rank test, and Cox regression were used
      to study recurrence-free survival (RFS) and distant metastasis-free survival
      (DMFS). HG remained a significant prognostic indicator in low GG tumors (P =
      0.003 for DMFS, P< 0.001 for RFS) but not in high GG tumors. HG grade 2 tumors
      differed significantly from HG grade 1 tumors, underlining the prognostic role of
      intermediate HG tumors. Additionally, GG could stratify HG 1 as well as HG 2
      tumors into distinct prognostic groups. HG and GG add independent prognostic
      information to each other. However, the prognostic effects of both HG and GG are
      time varying, with the hazard ratios of high HG and GG tumors being markedly
      attenuated over time.

PMID- 21845211
TI  - Resistant thyrotoxicosis in a patient with graves disease: a case report.
AB  - Background. Conventional management of thyrotoxicosis includes antithyroid drugs,
      radioactive iodine, and surgery while adjunctive treatment includes beta
      blockers, corticosteroids, inorganic iodide and iopanoic acid. Very rarely,
      patients may be resistant to these modalities and require additional management.
      Case Presentation. A 50-year-old lady presented with weight loss and palpitations
      diagnosed as atrial fibrillation. Her past history was significant for right
      thyroid lobectomy for thyrotoxicosis. Thyroid functions tests at this
      presentation showed free T4 of 6.63 ng/dl (normal range: 0.93-1.7) and TSH of
      <0.005 MUIU/mL (normal range: 0.4-4.0). She was given aspirin, propranolol,
      heparin and carbimazole; however free T4 failed to normalize. Switching to
      propylthiouracil (PTU) did not prove successful. She was then given high doses of
      prednisolone (1 mg/kg/day) and lithium (400 mg twice daily) which prepared the
      patient for radioactive iodine treatment by reducing free T4 levels (2.82 ng/dl).
      Two doses of radioactive iodine were then administered 6 months apart.
      Subsequently she became hypothyroid and was started on thyroid replacement
      therapy. Conclusion. This case highlights management options in patients with
      resistant thyrotoxicosis. Radioactive iodine and surgery are definitive modes of
      treatment in such complex cases while steroids and lithium play an important role
      in preparing patients for more definitive treatment.

PMID- 21845212
TI  - Reproductive Organ of Blow Fly, Chrysomya megacephala (Diptera: Calliphoridae):
      Ultrastructural of Testis.
AB  - This work presents the ultrastructure of testis of the medically important blow
      fly, Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) using light
      microscopy and electron microscopy. Reproductive organ of males was dissected to
      determine the testis in the pupal stage, 3-day-old flies and 7-day-old flies and
      observed under scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM). SEM displayed a smooth surface which is occasionally penetrated
      by tracheoles. TEM of the testis in the pupal stage presents the thick testis
      wall covering underdeveloped cells containing a variable size of an electron
      dense globule. For the 3-day-old males, the testicular wall is formed by an
      external layer, a peritoneal sheath, a muscular layer, a basement membrane, and a
      follicular epithelium. Follicular epithelium presented developing spermatozoa.
      Regarding the 7-day-old males, development of spermatozoa is apparent, displaying
      nucleus, centriolar adjunct, axoneme, and mitochondrial derivatives, with the 9 +
      9 + 2 microtubule pattern of axoneme.

PMID- 21845213
TI  - Measurement of photoreceptor layer in glaucoma: a spectral-domain optical
      coherence tomography study.
AB  - Objective. To measure and compare photoreceptor layer thickness between normal
      and glaucomatous eyes using spectral-domain optical coherence tomography (OCT).
      Methods. Thirty-eight healthy normal volunteers and 47 glaucoma patients were
      included in the analysis. One eye from each participant was randomly selected for
      macula imaging by a spectral-domain OCT (3D OCT-1000, Topcon, Tokyo, Japan). The
      foveal and parafoveal (1.5 mm from the fovea) outer nuclear layer (ONL) and inner
      and outer segments (IS+OS) layer thicknesses were measured by a single masked
      observer. The measurements were repeated 3 times in a random sample of 30 normal
      eyes to determine the repeatability coefficient and intraclass correlation
      coefficient. Results. The measurement variabilities of photoreceptor thickness
      were low. The respective intraclass correlation coefficients of ONL and IS+OS
      thicknesses were 0.96 (95% confidence interval: 0.94-0.98) and 0.82 (95%
      confidence interval 0.70-0.90). While there were no differences in parafoveal ONL
      and IS+OS thicknesses between normal and glaucoma groups (P <= .410), the foveal
      ONL thickness was greater in glaucomatous eyes (P = .011) than in normal eyes.
      Conclusions. Glaucomatous damage may involve structural change in the
      photoreceptor layer.

PMID- 21845214
TI  - Fundus Autofluorescence and Spectral Domain OCT in Central Serous
      Chorioretinopathy.
AB  - Background. To describe the standard autofluorescence (FAF), the near infrared
      autofluorescence (NIA) and optical coherence tomography (OCT) patterns in central
      serous chorioretinopathy, correlating them with fluorescein angiography. Methods.
      Cross-sectional observational study, in which patients with at least seven months
      of CSC underwent ophthalmologic examination, fundus photography, FAF, NIA,
      fluorescein angiography (FA), and spectral-domain OCT. Results. Seventeen eyes of
      thirteen patients were included. The presentation features were a mottled
      hyperFAF in the detached area and areas with pigment mottling. NIA images showed
      areas of hyperNIA similar to FAF and localized areas of hypoNIA, which correlated
      with the points of leakage in the FA. OCT showed pigment epithelium detachment at
      the location of these hypoNIA spots. Discussion. FAF showed increased presence of
      fluorophores in the area of retinal detachment, which is believed to appear
      secondary to lipofuscin accumulation in the RPE or the presence of debris in the
      subretinal fluid. NIA has been related to the choroidal melanin content and there
      were areas of both increased and decreased NIA, which could be explained by
      damage ahead the retina, basically RPE and choroid. These findings, along with
      the PEDs found in the areas of hypoNIA, support the notion of a primary choroidal
      disease in CSC.

PMID- 21845216
TI  - Clinical neurophysiology in Alzheimer's disease.

PMID- 21845215
TI  - Resveratrol, MicroRNAs, Inflammation, and Cancer.
AB  - MicroRNAs are short noncoding RNAs that regulate the expression of many target
      genes posttranscriptionally and are thus implicated in a wide array of cellular
      and developmental processes. The expression of miR-155 or miR-21 is upregulated
      during the course of the inflammatory response, but these microRNAs are also
      considered oncogenes due to their upregulation of expression in several types of
      tumors. Furthermore, it is now well established that inflammation is associated
      with the induction or the aggravation of nearly 25% of cancers. Therefore, the
      above microRNAs are thought to link inflammation and cancer. Recently,
      resveratrol (trans-3,4',5-trihydroxystilbene), a natural polyphenol with
      antioxidant, anti-inflammatory, and anticancer properties, currently at the stage
      of preclinical studies for human cancer prevention, has been shown to induce the
      expression of miR-663, a tumor-suppressor and anti-inflammatory microRNA, while
      downregulating miR-155 and miR-21. In this paper we will discuss how the use of
      resveratrol in therapeutics may benefit from the preanalyses on the status of
      expression of miR-155 or miR-21 as well as of TGFbeta1. In addition, we will
      discuss how resveratrol activity might possibly be enhanced by simultaneously
      manipulating the levels of its key target microRNAs, such as miR-663.

PMID- 21845217
TI  - Amylolytic microorganism from sao paulo zoo composting: isolation,
      identification, and amylase production.
AB  - Composting is a way of transforming the organic waste into fertilizer, minimizing
      the use of inorganic compounds that may contaminate the environment. This
      transformation is the result of the microorganism action, converting complex
      carbon sources into energy. Enzymes that are exported by the microorganisms to
      the surrounding environment mediate this process. The aiming of the present work
      is to prospect the compost produced by the organic composting unit (OCU) of the
      Fundacao Parque Zoologico de Sao Paulo (FPZSP) to find novel starch hydrolyzing
      organisms (SHO) that secrete large amounts of amylases under harsh conditions,
      such as high temperature. We found five bacterial isolates that have amylolytic
      activity induced by soluble starch and 39 degrees C temperature of growth. These
      bacterial strains were identified by MALDI-TOF (Matrix-assisted laser
      desorption/ionization-Time of Flight) analysis, a rapid and efficient methodology
      for microbe identification in large scale. Our results present amylolytic strains
      that belong to diverse taxonomic groups (Solibacillus silvestris, Arthrobacter
      arilaitensis, Isoptericola variabilis, and Acinetobacter calcoaceticus); some of
      them have never been associated with this kind of hydrolytic activity before. The
      information regarding enzyme induction will be important to optimize the
      production by the bacterial isolates, which may be a great value for
      biotechnological applications.

PMID- 21845218
TI  - Vascular stiffness and increased pulse pressure in the aging cardiovascular
      system.
AB  - Aging leads to a multitude of changes in the cardiovascular system, including
      systolic hypertension, increased central vascular stiffness, and increased pulse
      pressure. In this paper we will review the effects of age-associated increased
      vascular stiffness on systolic blood pressure, pulse pressure, augmentation
      index, and cardiac workload. Additionally we will describe pulse wave velocity as
      a method to measure vascular stiffness and review the impact of increased
      vascular stiffness as an index of vascular health and as a predictor of adverse
      cardiovascular outcomes. Furthermore, we will discuss the underlying mechanisms
      and how these may be modified in order to change the outcomes. A thorough
      understanding of these concepts is of paramount importance and has therapeutic
      implications for the increasingly elderly population.

PMID- 21845219
TI  - Nuts improve diet quality compared to other energy-dense snacks while maintaining
      body weight.
AB  - Previous studies have reported that regular nut consumption reduces
      cardiovascular disease (CVD) risk and does not promote weight gain despite the
      fact that nuts are energy-dense. However, no studies have investigated the body
      composition of those regularly consuming nuts compared to similar intakes of
      other snacks of equal energy density. This parallel study (n = 118) examined the
      effects of providing daily portions (~1100 kJ/d) of hazelnuts, chocolate, or
      potato crisps compared to a control group receiving no snacks for twelve weeks.
      Effects on body weight and composition, blood lipids and lipoproteins, resting
      metabolic rate (RMR), appetite indices, and dietary quality were compared. At
      week 12, there was no significant difference in any of the outcome measurements
      between the groups except for dietary quality, which improved significantly in
      the nut group. Nuts can be incorporated into the diet without adversely affecting
      body weight and can improve diet quality.

PMID- 21845220
TI  - Protein and Amino Acid Supplementation Does Not Alter Proteolytic Gene Expression
      following Immobilization.
AB  - Objective. To determine if supplementation of protein and amino acids (PAA)
      decreases skeletal muscle expression of atrophy-related genes, muscle mass, and
      strength during immobilization in humans. Methods. Twenty males wore a lower-limb
      immobilization boot for 28 days and consumed either a PAA supplement (28 g
      protein) or carbohydrate placebo (28 g maltodextrose), while consuming their
      normal daily diet. Testing sessions included dietary analysis, lower-leg girth
      and body composition measurements, strength testing, and gastrocnemius muscle
      biopsies. Muscle was analyzed for mRNA expression of markers in the ubiquitin and
      calpain systems, myostatin, TNF-alpha, and NF-kappaB. Results. All genes of
      interest increased over time (P < .05), but there was no difference between
      groups. Lower-leg girth decreased over time (P = 0.02); however, there were no
      significant changes in body composition or strength. Conclusion. Short-term lower
      limb disuse, despite the absence of significant muscle atrophy, is associated
      with increases in skeletal muscle gene expression of several proteolysis-related
      genes. These changes do not appear to be altered by oral PAA supplementation.

PMID- 21845221
TI  - NAFLD, Estrogens, and Physical Exercise: The Animal Model.
AB  - One segment of the population that is particularly inclined to liver fat
      accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is
      more common in men than in women, after menopause there is a reversal in gender
      distribution. At the present time, weight loss and exercise are regarded as first
      line treatments for NAFLD in postmenopausal women, as it is the case for the
      management of metabolic syndrome. In recent years, there has been substantial
      evidence coming mostly from the use of the animal model, that indeed estrogens
      withdrawal is associated with modifications of molecular markers favouring the
      activity of metabolic pathways ultimately leading to liver fat accumulation. In
      addition, the use of the animal model has provided physiological and molecular
      evidence that exercise training provides estrogens-like protective effects on
      liver fat accumulation and its consequences. The purpose of the present paper is
      to present information relative to the development of a state of NAFLD resulting
      from the absence of estrogens and the role of exercise training, emphasizing on
      the contribution of the animal model on these issues.

PMID- 21845222
TI  - Use of physiologic reasoning to diagnose and manage shock States.
AB  - Shock states are defined by stereotypic changes in well-known physiologic
      parameters. While these well-known changes provide a convenient entry point into
      further evaluation of patients in shock or at risk for shock, use of such
      physiologic evaluation is not commonly seen in clinical medicine. A formal
      description of physiologic reasoning in the diagnosis of shock states is
      presented in this paper. Included with this conceptual framework is a discussion
      of key tests or findings that can be used to differentiate between possible
      diagnoses, and the pairing of treatment strategies to distinct classes of
      physiologic abnormalities. It is hoped that the methodology presented here will
      demonstrate the primacy of physiologic reasoning in the diagnosis and treatment
      of hemodynamic instability. Advantages of this method are speed and accuracy,
      efficient use of resources, and mitigation against sources of medical errors.

PMID- 21845223
TI  - Disruption of circadian rhythms: a crucial factor in the etiology of depression.
AB  - Circadian factors might play a crucial role in the etiology of depression. It has
      been demonstrated that the disruption of circadian rhythms by lighting conditions
      and lifestyle predisposes individuals to a wide range of mood disorders,
      including impulsivity, mania and depression. Also, associated with depression,
      there is the impairment of circadian rhythmicity of behavioral, endocrine, and
      metabolic functions. Inspite of this close relationship between both processes,
      the complex relationship between the biological clock and the incidence of
      depressive symptoms is far from being understood. The efficiency and the timing
      of treatments based on chronotherapy (e.g., light treatment, sleep deprivation,
      and scheduled medication) indicate that the circadian system is an essential
      target in the therapy of depression. The aim of the present review is to analyze
      the biological and clinical data that link depression with the disruption of
      circadian rhythms, emphasizing the contribution of circadian desynchrony.
      Therefore, we examine the conditions that may lead to circadian disruption of
      physiology and behavior as described in depressive states, and, according to this
      approach, we discuss therapeutic strategies aimed at treating the circadian
      system and depression.

PMID- 21845224
TI  - Gene expression profiling in organ transplantation.
AB  - Aim of Review. Huge effort is being made among the transplant community
      investigating novel biomarkers that enable transplant clinicians to identify
      patients at risk for allograft rejection or those who will develop tolerance so
      that immunosuppression could be safely minimized or even ideally withdrawn.
      Despite the important advances achieved in the identification of several
      potential biomarkers of tolerance, rejection, or both, validation and
      demonstration of their clinical utility still needs to be tested, which will need
      international cooperative networks. It is important to note that the
      reproducibility of differently expressed genes might be affected by many factors
      such as gene ranking and selection methods, inherent differences between types,
      and the choice of thresholds. However, because microarray analyses are expensive
      and time consuming and their statistical evaluation is often very difficult, gene
      expression analysis using the RTPCR method is nowadays recommended. Conclusions.
      In the field of organ transplantation, gene-expression-based decision might help
      in improving patient and graft outcome and there are a multitude of studies
      showing that gene-expression profiling is feasible.

PMID- 21845225
TI  - Modeling drug-carrier interaction in the drug release from nanocarriers.
AB  - Numerous nanocarriers of various compositions and geometries have been developed
      for the delivery and release of therapeutic and imaging agents. Due to the high
      specific surface areas of nanocarriers, different mechanisms such as ion pairing
      and hydrophobic interaction need to be explored for achieving sustained release.
      Recently, we developed a three-parameter model that considers reversible drug
      carrier interaction and first-order drug release from liposomes. A closed-form
      analytical solution was obtained. Here, we further explore the ability of the
      model to capture the release of bioactive molecules such as drugs and growth
      factors from various nanocarriers. A parameter study demonstrates that the model
      is capable of resembling major categories of drug release kinetics. We further
      fit the model to 60 sets of experimental data from various drug release systems,
      including nanoparticles, hollow particles, fibers, and hollow fibers.
      Additionally, bootstrapping is used to evaluate the accuracy of parameter
      determination and validate the model in selected cases. The simplicity and
      universality of the model and the clear physical meanings of each model parameter
      render the model useful for the design and development of new drug delivery
      systems.

PMID- 21845226
TI  - Nonatonic obstetric haemorrhage: effectiveness of the nonpneumatic antishock
      garment in egypt.
AB  - The study aims to determine if the nonpneumatic antishock garment (NASG), a first
      aid compression device, decreases severe adverse outcomes from nonatonic
      obstetric haemorrhage. Women with nonatonic aetiologies (434), blood loss > 1000
      mL, and signs of shock were eligible. Women received standard care during the
      preintervention phase (226) and standard care plus application of the garment in
      the NASG phase (208). Blood loss and extreme adverse outcomes (EAO-mortality and
      severe morbidity) were measured. Women who used the NASG had more estimated blood
      loss on admission. Mean measured blood loss was 370 mL in the preintervention
      phase and 258 mL in the NASG phase (P < 0.0001). EAO decreased with use of the
      garment (2.9% versus 4.4%, (OR 0.65, 95% CI 0.24-1.76)). In conclusion, using the
      NASG improved maternal outcomes despite the worse condition on study entry. These
      findings should be tested in larger studies.

PMID- 21845227
TI  - The recurrent vulvovaginal candidiasis: proposal of a personalized therapeutic
      protocol.
AB  - Background. Recurrent vulvovaginal candidiasis (RVC) is an increasing challenge
      in clinical practice. Objective. The purpose of this study was to reduce the
      episodes of RVC through the intake of fluconazole 200 mg/dose with a personalized
      regimen at growing administration intervals with a probiotic. Method. 55 patients
      received a 200 mg fluconazole as an induction dose for 3 alternate days. Symptoms
      resolution after 10-14 days made the patients eligible to continue with a
      maintenance therapy of fluconazole weekly for one month, followed by 200 mg after
      10, 15, 20 and 30 days. Patients were allowed to move on to the next level of
      maintenance therapy only if they were symptom free. Patients were also given a
      probiotic with Beta Glucan and Echinacea Purpurea. Results. Among the 55 patients
      enrolled, four (7%) have withdrawn after the induction phase. 51 patients
      completed the whole therapeutic maintenance period, and eight (15,6%) experienced
      a recurrence before the end of the therapy. Five women (9,8%) relapsed (two after
      2 months and three after 6 months). Conclusion. The positive results of our study
      prove the effectiveness of an individualized protocol for a rather short period,
      with a slowly decreasing administration of fluconazole + probiotic.

PMID- 21845228
TI  - Clinical significance and prognostic impact of subcutaneous or intrastrap
      muscular recurrence of papillary thyroid carcinoma.
AB  - Subcutaneous or intrastrap muscular (SIM) recurrence is rare in papillary thyroid
      carcinoma (PTC) patients, and its clinical significance remains unclear. We
      analyzed 29 patients with PTC who showed SIM recurrence in order to elucidate
      this issue. The incidence of patient age 55 years or older at initial surgery,
      extrathyroid extension, and clinically detected lymph node metastasis was 83%,
      35%, and 46%, respectively. After surgical dissection, 17% of patients showed
      repeated SIM recurrence. Distant recurrence was detected in 45% of patients and
      was more likely to occur in patients with high-risk clinicopathological features.
      In all but one patient in this series, distant recurrence was detected at the
      same time or after the detection of SIM recurrence. Three patients died of PTC,
      but none of these patients died of the development of recurrent SIM lesions.
      These findings suggest that although SIM recurrence is a rare event and is not
      fatal, it is a predictor of distant recurrence especially in patients with high
      risk clinicopathological features. Careful followup is recommended for such
      patients.

PMID- 21845229
TI  - The need for the pathology community to sponsor a whole slide imaging repository
      with technical guidance from the pathology informatics community.

PMID- 21845230
TI  - A data model and database for high-resolution pathology analytical image
      informatics.
AB  - BACKGROUND: The systematic analysis of imaged pathology specimens often results
      in a vast amount of morphological information at both the cellular and sub
      cellular scales. While microscopy scanners and computerized analysis are capable
      of capturing and analyzing data rapidly, microscopy image data remain
      underutilized in research and clinical settings. One major obstacle which tends
      to reduce wider adoption of these new technologies throughout the clinical and
      scientific communities is the challenge of managing, querying, and integrating
      the vast amounts of data resulting from the analysis of large digital pathology
      datasets. This paper presents a data model, which addresses these challenges, and
      demonstrates its implementation in a relational database system. CONTEXT: This
      paper describes a data model, referred to as Pathology Analytic Imaging Standards
      (PAIS), and a database implementation, which are designed to support the data
      management and query requirements of detailed characterization of micro-anatomic
      morphology through many interrelated analysis pipelines on whole-slide images and
      tissue microarrays (TMAs). AIMS: (1) Development of a data model capable of
      efficiently representing and storing virtual slide related image, annotation,
      markup, and feature information. (2) Development of a database, based on the data
      model, capable of supporting queries for data retrieval based on analysis and
      image metadata, queries for comparison of results from different analyses, and
      spatial queries on segmented regions, features, and classified objects. SETTINGS
      AND DESIGN: The work described in this paper is motivated by the challenges
      associated with characterization of micro-scale features for comparative and
      correlative analyses involving whole-slides tissue images and TMAs. Technologies
      for digitizing tissues have advanced significantly in the past decade. Slide
      scanners are capable of producing high-magnification, high-resolution images from
      whole slides and TMAs within several minutes. Hence, it is becoming increasingly
      feasible for basic, clinical, and translational research studies to produce
      thousands of whole-slide images. Systematic analysis of these large datasets
      requires efficient data management support for representing and indexing results
      from hundreds of interrelated analyses generating very large volumes of
      quantifications such as shape and texture and of classifications of the
      quantified features. MATERIALS AND METHODS: We have designed a data model and a
      database to address the data management requirements of detailed characterization
      of micro-anatomic morphology through many interrelated analysis pipelines. The
      data model represents virtual slide related image, annotation, markup and feature
      information. The database supports a wide range of metadata and spatial queries
      on images, annotations, markups, and features. RESULTS: We currently have three
      databases running on a Dell PowerEdge T410 server with CentOS 5.5 Linux operating
      system. The database server is IBM DB2 Enterprise Edition 9.7.2. The set of
      databases consists of 1) a TMA database containing image analysis results from
      4740 cases of breast cancer, with 641 MB storage size; 2) an algorithm validation
      database, which stores markups and annotations from two segmentation algorithms
      and two parameter sets on 18 selected slides, with 66 GB storage size; and 3) an
      in silico brain tumor study database comprising results from 307 TCGA slides,
      with 365 GB storage size. The latter two databases also contain human-generated
      annotations and markups for regions and nuclei. CONCLUSIONS: Modeling and
      managing pathology image analysis results in a database provide immediate
      benefits on the value and usability of data in a research study. The database
      provides powerful query capabilities, which are otherwise difficult or cumbersome
      to support by other approaches such as programming languages. Standardized,
      semantic annotated data representation and interfaces also make it possible to
      more efficiently share image data and analysis results.

PMID- 21845231
TI  - Computer-aided identification of prostatic adenocarcinoma: Segmentation of
      glandular structures.
AB  - BACKGROUND: Identification of individual prostatic glandular structures is an
      important prerequisite to quantitative histological analysis of prostate cancer
      with the aid of a computer. We have developed a computer method to segment
      individual glandular units and to extract quantitative image features, for
      computer identification of prostatic adenocarcinoma. METHODS: TWO SETS OF DIGITAL
      HISTOLOGY IMAGES WERE USED: database I (n = 57) for developing and testing the
      computer technique, and database II (n = 116) for independent validation. The
      segmentation technique was based on a k-means clustering and a region-growing
      method. Computer segmentation results were evaluated subjectively and also
      compared quantitatively against manual gland outlines, using the Jaccard
      similarity measure. Quantitative features that were extracted from the computer
      segmentation results include average gland size, spatial gland density, and
      average gland circularity. Linear discriminant analysis (LDA) was used to combine
      quantitative image features. Classification performance was evaluated with
      receiver operating characteristic (ROC) analysis and the area under the ROC curve
      (AUC). RESULTS: Jaccard similarity coefficients between computer segmentation and
      manual outlines of individual glands were between 0.63 and 0.72 for non-cancer
      and between 0.48 and 0.54 for malignant glands, respectively, similar to an
      interobserver agreement of 0.79 for non-cancer and 0.75 for malignant glands,
      respectively. The AUC value for the features of average gland size and gland
      density combined via LDA was 0.91 for database I and 0.96 for database II.
      CONCLUSIONS: Using a computer, we are able to delineate individual prostatic
      glands automatically and identify prostatic adenocarcinoma accurately, based on
      the quantitative image features extracted from computer-segmented glandular
      structures.

PMID- 21845232
TI  - In Vitro and In Vivo Pre-Clinical Analysis of a F(ab')(2) Fragment of Panitumumab
      for Molecular Imaging and Therapy of HER1 Positive Cancers.
AB  - BACKGROUND: The objective of this study was to characterize the in vitro and in
      vivo properties of the F(ab')(2) fragment of panitumumab and to investigate its
      potential for imaging and radioimmunotherapy. METHODS: The panitumumab F(ab')(2)
      was generated by enzymatic pepsin digestion. After the integrity and
      immunoreactivity of the F(ab')(2) was evaluated, the fragment was radiolabeled.
      In vivo studies included direct quantitation of tumor targeting and normal organ
      distribution of the radiolabeled panitumumab F(ab')(2) as well as planar gamma
      scintigraphy and PET imaging. RESULTS: The panitumumab F(ab')(2) was successfully
      produced by peptic digest. The F(ab')(2) was modified with the CHX-A"-DTPA
      chelate and efficiently radiolabeled with either (111)In or (86)Y. In vivo tumor
      targeting was achieved with acceptable uptake of radioactivity in the normal
      organs. The tumor targeting was validated by both imaging modalities with good
      visualization of the tumor at 24 h. CONCLUSIONS: The panitumumab F(ab')(2)
      fragment is a promising candidate for imaging of HER1 positive cancers.

PMID- 21845235
TI  - Viability analysis of subepithelial connective tissue grafts subjected to a
      mechanical expansion process: a histologic study in dogs.
AB  - The aim of this study was to histologically evaluate the viability of
      mechanically expanded subepithelial connective tissue grafts. Sixteen samples of
      palatal connective tissue were collected from eight beagle dogs. Half of the
      samples were subjected to the expansion procedure and used as subepithelial
      grafts in the canine region, and the samples not subjected to expansion were
      grafted at the contralateral side. After 60 days, biopsies were collected and
      examined histologically by light and confocal laser microscopy and
      immunohistochemically with anti-CD31 antibody for endothelial cells. There were
      no significant differences between the control and test groups. It was concluded
      that this new method to expand the area of connective tissue grafts was not only
      viable biologically, but also decreased surgical risks without increasing
      processing time.

PMID- 21845236
TI  - Reconstruction of the interdental papilla with an underlying subepithelial
      connective tissue graft: technical considerations and case reports.
AB  - This article introduces a surgical technique developed to achieve soft tissue
      augmentation of the interproximal space. The technique was designed to minimize
      surgical trauma and blockage of blood supply to the existing papilla by accessing
      the papillary area through vertical incisions and by elevating a single full
      thickness flap without disrupting the papillary bridge. A free connective tissue
      graft was placed beneath the undermined papilla and secured with sutures.
      Advantages and variations of the technique are discussed.

PMID- 21845237
TI  - Effect of air polishing with glycine and bicarbonate powders on a nanocomposite
      used in dental restorations: an in vitro study.
AB  - Air polishing increases the surface roughness of dental restorations, enhancing
      bacterial adhesion. This in vitro study was the first, to the authors' knowledge,
      to evaluate the effect of sodium bicarbonate and glycine powders, at different
      application distances (2 and 7 mm) and times (5, 10, and 30 seconds), on the
      surface roughness of a nanocomposite material used in restorations. Untreated
      slides were used as controls. Surface roughness was measured using atomic force
      microscopy. Air polishing with glycine powder for 5 seconds, at both application
      distances, determined the lowest surface damage. Even with all the limitations of
      any in vitro analysis, this study further supports the safety of this method of
      air polishing.

PMID- 21845238
TI  - Connective tissue graft and resin glass ionomer for the treatment of gingival
      recession associated with noncarious cervical lesions: a case series.
AB  - This article describes the treatment of gingival recession associated with
      noncarious cervical lesions by a connective tissue graft in combination with a
      resin-modified glass-ionomer restoration (CTG + R). Eleven patients showing the
      association of recession and lesions were selected and treated by CTG + R.
      Bleeding on probing, probing depth, relative gingival recession, clinical
      attachment level, noncarious cervical lesion height, and dentin sensitivity were
      measured. The treatment provided statistically significant gains in clinical
      attachment level and shallow probing depths. The percentage of cervical lesion
      height covered was 74.0% +/- 22.90%. It can be concluded that the presence of
      resin-modified glass-ionomer filling did not interfere with coverage achieved by
      the connective tissue graft.

PMID- 21845239
TI  - Effect of physical and physicochemical surface treatment methods on the tensile
      strength of CAD/CAM-fabricated zirconia posts and cores luted to root canals.
AB  - This study investigated the effect of surface treatments on the retentive
      strength of zirconia posts and cores to root canals. Maxillary central incisors
      (n = 40) were treated endodontically, obturated, and post spaces were prepared.
      Zirconia posts and cores (n = 40) were obtained and assigned randomly to four
      groups (n = 10 per group; control, sandblasting, tribochemical silica coating,
      and tribochemical silica coating + silanization). Posts were cemented adhesively,
      and tensile force was applied. All treatment methods increased the tensile
      strength of zirconia posts and cores compared to the control group (P = .034). No
      significant difference was found between treatment methods. Failure types varied
      depending on the surface treatment method.

PMID- 21845240
TI  - Long-term onlay graft volume maintenance in aggressive periodontitis patients.
AB  - Treatment planning in the esthetic zone has classically presented some of the
      greatest challenges to the practitioner. The purpose of this article is to
      describe a staged, multidisciplinary approach and follow-up to a case of
      aggressive periodontitis. Microbial sampling for suspected periodontopathogens
      was taken before and after treatment. Qualitative polymerase chain reaction
      analysis was done to detect the presence of cytomegalovirus and Epstein-Barr
      virus type 1 6 years after active periodontal therapy. A control computed
      tomography scan taken 5.5 years postaugmentation showed stable bone levels and
      excellent volume maintenance of the transplanted block graft.

PMID- 21845241
TI  - Analysis of tissue neogenesis in extraction sockets treated with guided bone
      regeneration: clinical, histologic, and micro-CT results.
AB  - The aims of this article were to perform a detailed evaluation of the healing of
      extraction sockets covered with a resorbable collagen membrane 12 weeks following
      exodontia and to determine if this device had ossifying properties. Ten
      consecutive subjects in need of extraction of maxillary premolars were recruited.
      Each subject had a hopeless maxillary premolar extracted with minimal trauma.
      Sockets were then covered with a collagen barrier membrane alone. At 12 weeks,
      reentry surgery was performed, clinical measurements were repeated, and bone core
      biopsies were obtained prior to dental implant placement for histologic and
      microcomputed tomography (micro-CT) analysis. Study sites showed mean bone
      regeneration horizontally of 7.7 mm (buccopalatally) and 4.6 mm (mesiodistally).
      Vertical bone repair showed a mean gain of 10.9 mm. Subtraction radiography
      showed a mean apical shift of the crestal bone at the center of the socket of 2.1
      mm (range, 0.7 to 4.3 mm). Micro-CT and histology revealed formation of well
      mineralized tissue at 12 weeks, with a mean percentage of vital bone of 45.87% +/
      12.35%. No signs of membrane ossification were observed. A detailed analysis of
      tissue neogenesis in extraction sites protected by this barrier membrane has
      demonstrated that adequate bone formation for implant placement occurs as early
      as 12 weeks following exodontia, with minimal changes in alveolar ridge
      dimensions. No evidence of membrane ossification was observed.

PMID- 21845242
TI  - Reduction of tooth loss associated with periodontal treatment.
AB  - Comparing tooth loss for populations comprising subjects with periodontal disease
      has been limited by broad and different definitions of disease severity. Numeric
      scores for periodontal disease severity and risk were used to enhance the
      precision of comparing tooth loss for two populations. Both populations received
      routine dental care, but only one received comprehensive periodontal treatment.
      The analysis provides evidence that adding periodontal treatment to routine
      dental care is associated with less tooth loss and more patients who do not lose
      any teeth. Furthermore, it may be possible to nearly eliminate tooth loss
      associated with periodontal disease.

PMID- 21845244
TI  - Anatomical crown width/length ratios of worn and unworn maxillary teeth in Asian
      subjects.
AB  - Crown width/length ratios have been considered an important aspect in the
      esthetic zone. Because previous investigations focused on Caucasian populations,
      limited information is available on other ethnic groups to propose a
      comprehensive approach to anterior maxillary teeth. The purpose of this study was
      to analyze the dimensions of anatomical crowns of maxillary anterior tooth groups
      with respect to width, length, and width/length ratios among an Asian population.
      The tooth dimensions presented in this investigation may serve as guidelines for
      treatment planning in restorative dentistry and periodontal surgery for this
      particular ethnic group.

PMID- 21845243
TI  - Human buccal plate extraction socket regeneration with recombinant human platelet
      derived growth factor BB or enamel matrix derivative.
AB  - The objective of this study was to assess the osseous healing of buccal plate
      extraction socket defects. There were four cohorts: group A (mineral collagen
      bone substitute [MCBS] scaffold alone), group B (MCBS with recombinant human
      platelet-derived growth factor BB [rhPDGF-BB; 0.3 mg/mL]), group C (MCBS with
      enamel matrix derivative [EMD]), and group D (combination of EMD with bone
      ceramic). The primary outcome of bone quality was evaluated using light
      microscopy, backscatter scanning electron microscopy, and histomorphometrics.
      Reentry surgery provided an opportunity for clinical observation of the healed
      ridge morphology. Sixteen patients with buccal wall extraction socket defects
      were randomized into four treatment groups of equal size. Grafting was provided
      at the time of extraction with advancement of the buccal flap for primary
      closure. A trephine core biopsy of the implant site preparation was performed
      after 5 months for implant placement. Histologic examination identified new bone
      healing around the biomaterial scaffolds. Statistically significant differences
      in new bone formation were not observed among the treatment groups. There was a
      histomorphometric trend toward more new bone for the rhPDGF-BB-treated group
      (group B). This group had the most favorable ridge morphology for optimal implant
      placement.

PMID- 21845245
TI  - Management of a coronally advanced lingual flap in regenerative osseous surgery:
      a case series introducing a novel technique.
AB  - One of the crucial factors in the success of guided bone regeneration procedures
      is the correct management of the soft tissues. This allows for stable primary
      wound closure without tension, which can result in premature exposure of the
      augmentation area, jeopardizing the final outcome. The use of vertical and
      periosteal incisions to passivate buccal and lingual flaps in the posterior
      mandible is often limited by anatomical factors. This paper reports on a series
      of 69 consecutive cases introducing a novel surgical technique to release and
      advance the lingual flap coronally in a safe and predictable manner.

PMID- 21845246
TI  - Human histologic verification of osseointegration of an immediate implant placed
      into a fresh extraction socket with excessive gap distance without primary flap
      closure, graft, or membrane: a case report.
AB  - The aim of this research was to verify clinically and histologically whether an
      excessively large horizontal and vertical gap distance of an implant placed into
      an immediate extraction socket would osseointegrate coronally at the implant
      socket interface without primary flap closure, a bone graft, or a barrier
      membrane. An immediate implant and straight-profile healing abutment were placed
      at the palatal aspect of the extraction socket replacing a nonrestorable
      maxillary left canine. The residual horizontal defect measured 4.2 mm
      buccolingually and was allowed to heal by secondary intention. The implant was
      loaded after 5 months and biopsied after 10 months of placement, using the
      coronal portion of the buccal bone. The histologic section of the coronal aspect
      of the implant interface revealed intimate bone contact to the first thread.
      There was reestablishment of the implant biologic width coronal to the bone
      contact with connective tissue and junctional epithelium. This case report
      provides clinical and histologic proof that the immediate placement of implants
      into extraction sockets with an intact buccal wall allows healing and
      osseointegration despite a large gap distance and without primary flap closure, a
      bone graft, or a barrier membrane.

PMID- 21845247
TI  - Biologic rationale of esthetic crown lengthening using innovative proportion
      gauges.
AB  - Research shows that practitioners tend to underestimate the amount of tooth
      structure that must be exposed during a crown lengthening procedure. In the
      anterior portion of the mouth, this can lead to biologic width problems and
      subsequent cosmetic issues. This paper presents a biologically based, step-by
      step approach to periodontal esthetic crown lengthening. Using a series of
      innovative measuring gauges, the ideal clinical crown length of a tooth as well
      as the proper occlusogingival placement of the interproximal papilla will be
      determined based on established, documented tooth proportion relationships. The
      biologic crown length of the tooth, defined as the distance from the incisal edge
      to the bone crest, will subsequently be determined as a function of the clinical
      crown length, with the ultimate goals being adequate tooth structure for the
      placement of a restorative margin, establishment of a healthy dentogingival
      complex, and the placement of an esthetically pleasing definitive restoration.

PMID- 21845248
TI  - Clinical and histologic evaluation of fresh frozen human bone grafts for
      horizontal reconstruction of maxillary alveolar ridges.
AB  - The aims of the present study were to clinically and histologically evaluate
      human fresh frozen bone (FFB) grafts used to treat severe maxillary horizontal
      defects prior to dental implant placement. Ten patients were treated with FFB
      onlay grafts. Measurements using computed tomography scans were recorded
      preoperatively and at 5 months. Six core biopsies were retrieved and processed
      for light microscopy. At baseline, thickness of the maxillary alveolar ridge
      measured 2.3 +/- 0.4 mm; it measured 6.8 +/- 0.5 mm after reconstruction. All
      implants were successful after 24 months. Histologic results showed that FFB
      blocks and new bone were integrated perfectly. Histomorphometry revealed a mean
      percentage of bone of 57.5% +/- 24.7%.

PMID- 21845249
TI  - Prospective evaluation of the use of motorized ridge expanders in guided bone
      regeneration for future implant sites.
AB  - The purposes of this prospective, randomized, controlled clinical investigation
      were to evaluate the performance of motorized ridge expanders (MREs) and to
      compare their results with those achieved using lateral ridge augmentation (LRA).
      Eight subjects with bilateral ridge deformities were selected. One technique was
      used on the right side and the other on the left. Implants were placed 6 months
      after bone augmentation procedures. All measurements were recorded at 2 and 5 mm
      from the most coronal aspect of the crest. The augmentation achieved with both
      techniques was statistically significant: 1.2 mm for LRA and 1.5 mm for MRE 2 mm
      from the crest and 1.5 mm for LRA and 1.6 mm for MRE at 5 mm from the crest. The
      differences between the two techniques were statistically insignificant. The
      amount of expansion achieved in the MRE sites appeared to be negatively
      correlated with the thickness of the cancellous bone (P < .05), and it was not
      affected by the thickness of the cortical plate. The MRE technique appears to be
      as effective as the LRA technique in augmenting the thickness of atrophic ridges.
      Defects treated with MREs showed less bone width contraction during the first 6
      months of healing.

PMID- 21845251
TI  - Controlled synthesis of semiconductor nanostructures in the liquid phase.
AB  - The microstructure (composition, size and shape etc.) of semiconductor
      nanocrystals determine the electronic density of states of semiconductor
      nanomaterials and ultimately determine their optical and electrical properties.
      Semiconductor nanocrystal advanced structures, such as hybrid nanostructures and
      nanocrystal superlattices, not only integrate the function of individual
      nanocrystals, but also brings the materials collective and synchronic properties.
      How to control the monodispersity, composition and structure of as-prepared
      semiconductor nanocrystals during their syntheses, as well as their furthermore
      assembly, has been a hot research area in this decade. This critical review
      focuses on the development of synthetic and assembly methods (techniques) of
      semiconductor nanocrystals processed in the liquid phase. Emphasis is on the
      synthesis methodology, microstructure related properties of semiconductor
      nanocrystals, and their applications (243 references).

PMID- 21845250
TI  - Rational basis for the use of a new clinical procedure in immediately loaded
      implant rehabilitations: a case report.
AB  - This report presents a new clinical protocol that facilitates the diagnostic,
      surgical, and prosthetic phases of immediately loaded implant rehabilitations.
      The proposed technique aims to simplify recording of the centric relation, which
      is usually done immediately after surgery, during the surgical impression phase.
      This shortens operative time while meeting requirements for an accurate
      impression and is thus simple and cost effective. The case report of a maxillary
      full-arch immediately loaded implant rehabilitation in a 45-year-old patient
      illustrates the clinical steps in the proposed procedure and confirms its
      repeatability.

PMID- 21845252
TI  - Crystal structures and magnetism of infinite alternating chains arranged by
      paddle-wheel dinuclear copper and mononuclear copper units.
AB  - The crystal structures and magnetic properties of two novel polyclusters
      {[Cu(3)(tci)(2)(H(2)O)(2)].12H(2)O}(n) (1) and
      {[Cu(3)(tci)(2)(H(2)O)(2)].6H(2)O}(n) (2) (tci = tris(2-carboxyethyl)
      isocyanurate) are investigated. The X-ray crystallographic analysis reveals that
      they contain interesting infinite alternating chains of dinuclear paddle-wheel
      copper and mononuclear copper units arranged in ABBA magnetism exchange mode.
      Variable-temperature magnetic susceptibility measurements on the two polyclusters
      show strong antiferromagnetism couplings between copper ions with exchange
      interactions J = -181.4 cm(-1), zj' = -0.31 cm(-1) for 1, J = -170 cm(-1), zj' = 
      0.42 cm(-1) for 2. With the aim of studying magneto-structural correlation, we
      synthesized a three-dimensional polymer [Cu(3)(tci)(2)(py)(4)(H(2)O)(2)](n) (3)
      based on isolated dinuclear cluster and mononuclear copper units. Fitting the
      susceptibility data yielded J = -176.1 cm(-1), zj' = -0.084 cm(-1) for 3.

PMID- 21845253
TI  - Tanning salons and skin cancer.
AB  - Indoor tanning has substantially grown in USA and Europe, more especially in the
      sun-deprived Northern countries, but also in more sunny countries such as
      Queensland, Australia. Several studies have specifically addressed the prevalence
      of sunbed use by children and adolescents in Northern Europe and in the USA, and
      showed that up to 40-50% of teenagers 15-18 years old had ever used indoor
      tanning, the highest figures being observed among girls in Scandinavia and
      Minnesota. Indoor tanning among adults is mostly prevalent in age classes younger
      than 45. Epidemiological studies have shown that exposure to sunbeds increases
      the risk of both melanoma and non-melanoma skin cancers: a meta-analysis of 19
      studies published before 2006 showed that ever-use of sunbeds was positively
      associated with melanoma (summary relative risk, 1.15; 95% CI, 1.00-1.31), and
      first exposure before 35 years of age significantly increased melanoma risk (7
      studies, RR = 1.75; 95% CI, 1.35-2.26). Further epidemiological data documented
      the links between artificial UV tanning and melanoma: two large case-control
      studies in Minnesota and Australia yielded higher melanoma risks for ever use of
      sunbeds: 1.74 (95%CI, 1.42-2.14) and 1.41 (95%CI, 1.01-1.96) respectively, risk
      increasing with greater use and earlier age at first use. The most compelling
      evidence derives from a large cohort of Norwegian and Swedish women which showed
      that melanoma risk increased with accumulating exposure (RR for solarium use >=1
      time per month in two or three decades, 10-39 years, 2.37 (95%CI, 1.37-4.08)). In
      addition, the analysis of a melanoma epidemic observed in Iceland between 1995
      and 2002, on the trunk of women younger than 50, pointed out the possible role of
      the explosion of exposure to sunbeds in this country after 1985. Exposure to
      artificial ultraviolet is a risk factor for melanoma. Risk appears modest in the
      general population, but concentrates in the population that started sunbed use
      before the age of 35; the risk attributable to sunbed use in melanoma patients
      younger than 30 may be as high as 43 to 76%. Of particular concern is the use of
      sunbeds by adolescents. Use of sunbeds should be strongly discouraged, and banned
      under the age of 18.

PMID- 21845254
TI  - Preparation of hybrid mesoporous silica luminescent nanoparticles with
      lanthanide(III) complexes and their exhibition of white emission.
AB  - We chose dipicolinic acid as a tridentate chelating unit featuring ONO donors to
      react with lanthanide(III) ions to yield tight and protective N(3)O(6)
      environments around the lanthanide(III) ions. We immobilized the lanthanide(III)
      dipicolinic acid complexes on colloidal mesoporous silica with diameter smaller
      than 100 nm by a covalent bond grafting technique and obtained nearly
      monodisperse luminescent Eu-dpa-Si and Tb-dpa-Si functionalized hybrid mesoporous
      silica nanomaterials. These hybrid nanomaterials were characterized by powder X
      ray diffraction, scanning electron microscopy, transmission electron microscopy,
      thermogravimetric analysis, nitrogen adsorption-desorption, and photoluminescence
      spectroscopic techniques. The hybrid mesoporous silica nanoparticles exhibit
      intense emission lines upon UV-light irradiation, owing to the effective
      intramolecular energy transfer from the chromophore to the central lanthanide
      Eu(3+) and Tb(3+) ions. Furthermore, the functionalized nanomaterials can be
      turned to white light materials after annealing at high temperature.

PMID- 21845255
TI  - Synthesis of a chloro protected iridium nitrido complex.
AB  - Intramolecular activation processes of vulnerable ligand C-H bonds frequently
      limit the thermal stability and accessibility of late transition metal complexes
      with terminal metal nitrido units. In this study chloro substitution of the 2,6
      ketimine N-aryl substituents (2,6-C(6)H(3)R(2), R = Cl) of the pyridine, diimine
      ligand is probed to increase the stability of square-planar iridium nitrido
      compounds. The thermal stability of iridium azido precursor and nitrido compounds
      was studied by a combination of thermoanalytical methods (DTG/MS and DSC) and
      were compared to the results for the related complexes with 2,6-dialkyl
      substituted N-aryl groups (R = Me, iPr). The investigations were complemented by
      DFT calculations, which allowed us to unravel details of the thermal
      decomposition pathways and provided mechanistic insights of further conversion
      steps and fluctional processes. The DTG/MS and DSC measurements revealed two
      different types of thermolysis pathways for the azido compounds. For the
      complexes with R = Cl and iPr substituents, two well-separated exothermic
      processes were observed. The first moderately exothermic loss of N(2) is followed
      by a second, strongly exothermic transformation. This contrasts the experimental
      results for the compound with 2,6-dimethyl substituents (R = Me), where both
      steps proceed concurrently in the same temperature range. The separation of the
      two thermal steps in the 2,6-dichloro substituted derivative allowed us to
      develop a protocol for the isolation of the highly insoluble nitrido complex,
      which was characterized by UV/vis, IR-spectroscopy and elemental analysis. Its
      constitution was further confirmed by reaction with silanes, which gave the
      corresponding silyl amido complexes.

PMID- 21845256
TI  - Inhibiting metastasis of breast cancer cells in vitro using gold nanorod-siRNA
      delivery system.
AB  - Breast cancer is the most common malignant disease in women, and it is not the
      primary tumor but its metastasis kills most patients with breast cancer. Anti
      metastasis therapy based on RNA interference (RNAi) is emerging as one of
      promising strategies in tumor therapy. However, construction of an efficient
      delivery system for siRNA is still one of the major challenges. In this work,
      siRNA against protease-activated receptor-1 (PAR-1) which is a pivotal gene
      involved in tumor metastasis was conjugated to gold nanorods (AuNRs) via
      electrostatic interaction and delivered to highly metastatic human breast cancer
      cells. It was demonstrated that the siRNA oligos were successfully delivered into
      the cancer cells and mainly located in vesicle-like structures including
      lysosome. After transfected with the complex of AuNRs and PAR-1 siRNA (AuNRs@PAR
      1 siRNA), expression of PAR-1 at both mRNA and protein levels were efficiently
      down regulated, as evidenced by quantitative real time PCR and flow cytometry
      analysis, respectively. Transwell migration assay confirmed the decrease in
      metastatic ability of the cancer cells. The silencing efficiency of the complex
      was in-between that of TurboFect and Lipofectamine, however, the cytotoxicity of
      the AuNRs was lower than that of the latter two. Taken together, AuNRs with PAR-1
      siRNA are suited for RNAi based anti-metastasis therapy.

PMID- 21845257
TI  - Hydrogen peroxide sensors for cellular imaging based on horse radish peroxidase
      reconstituted on polymer-functionalized TiO2 nanorods.
AB  - We describe the reconstitution of apo-horse radish peroxidase (apo-HRP) onto
      TiO(2) nanorods functionalized with a multifunctional polymer. After
      functionalization, the horse radish peroxidase (HRP) functionalized TiO(2)
      nanorods were well dispersible in aqueous solution, catalytically active and
      biocompatible, and they could be used to quantify and image H(2)O(2) which is a
      harmful secondary product of cellular metabolism. The shape, size and structure
      of TiO(2) nanorods (anatase) were analyzed by transmission electron microscopy
      (TEM), high resolution TEM (HRTEM), electron diffraction (ED) and X-ray
      diffraction (XRD). The surface functionalization, HRP reconstitution and
      catalytic activity were confirmed by UV-Vis, FT-IR, CLSM and atomic force
      microscopy (AFM). Biocompatibility and cellular internalization of active HRP
      reconstituted TiO(2) nanorods were confirmed by a classical MTT cytotoxicity
      assay and confocal laser scanning microscopy (CLSM) imaging, respectively. The
      intracellular localization allowed H(2)O(2) detection, imaging and quantification
      in HeLa cells. The polymer functionalized hybrid system creates a complete sensor
      including a "cell positioning system" in each single particle. The flexible
      synthetic concept with functionalization by post-polymerization modification
      allows introduction of various dyes for sensitisation at different wavelengths
      and introduction of various anchor groups for anchoring on different particles.

PMID- 21845258
TI  - Si/PEDOT:PSS core/shell nanowire arrays for efficient hybrid solar cells.
AB  - A solution filling and drying method has been demonstrated to fabricate
      Si/PEDOT:PSS core/shell nanowire arrays for hybrid solar cells. The hybrid
      core/shell nanowire arrays show excellent broadband anti-reflection, and
      resulting hybrid solar cells absorb about 88% of AM 1.5G photons in the 300-1100
      nm range. The power conversion efficiency (PCE) of the hybrid solar cell reaches
      6.35%, and is primarily limited by direct and indirect interfacial recombination
      of charge carriers.

PMID- 21845259
TI  - Pt(II)-activated coupling of aminoethylferrocene with benzonitrile. A facile
      access route to a new redox-active bis(ferrocenyl-amidine) anion sensor.
AB  - A new heterometallic electroactive compound having the ferrocenyl moiety attached
      to the platinum atom through an amidine functionality has been prepared via
      Pt(II)-mediated nucleophilic addition of beta-aminoethylferrocene to a
      benzonitrile ligand. This neutral receptor shows remarkable electrochemical anion
      sensing redox response to H(2)PO(4)(-).

PMID- 21845260
TI  - Ligand-mediated shape control in the solvothermal synthesis of titanium dioxide
      nanospheres, nanorods and nanowires.
AB  - A versatile synthetic method, based on a solvothermal synthesis technique, has
      been developed for the fabrication of TiO(2) nanocrystals with different shapes,
      such as nanowires, nanorods and nanospheres. The central characteristic of our
      approach is the production of a coordination complex at an intermediate stage of
      the reaction that possesses appropriate symmetry using two distinct ligands,
      oleic acid and oleylamine. Those ligands have different binding strengths, which
      specifically dictate the shape of both the coordination complex and the resulting
      TiO(2) nanostructures. Additionally, this approach yields, for the first time,
      monodisperse, 4 nm anatase TiO(2) nanocrystals by controlling the symmetry of the
      intermediate and solvothermal conditions.

PMID- 21845261
TI  - Synthesis of the C19 methyl ether of aspercyclide A via germyl-Stille
      macrocyclisation and ELISA evaluation of both enantiomers following optical
      resolution.
AB  - Aspercyclide A (1) is a biaryl ether containing 11-membered macrocyclic natural
      product antagonist of the human IgE-FcepsilonRI protein-protein interaction
      (PPI); a key interaction in the signal transduction pathway for allergic
      disorders such as asthma. Herein we report a novel approach to the synthesis of
      the C19 methyl ether of aspercyclide A, employing a Pd(0)-catalysed, fluorous
      tagged alkenylgermane/arylbromide macrocyclisation (germyl-Stille reaction) as
      the key step, and evaluation of both enantiomers of this compound via ELISA
      following optical resolution by CSP-HPLC. A crystal structure for germyl hydride
      27 is also reported.

PMID- 21845267
TI  - Facile derivatization of azide ions using click chemistry for their sensitive
      detection with LC-MS.
AB  - By employing a click reaction, a novel method was developed for the sensitive
      detection of inorganic azides at as low as 21 ppb.

PMID- 21845268
TI  - Nanohybridization of ferrocene clusters and reduced graphene oxides with enhanced
      lithium storage capability.
AB  - Reduced graphene oxide (rGO) sheets attached with ferrocene were prepared, which
      showed improved lithium storage performance, especially at high current
      densities. Here, the ferrocene improves the specific capacity while the rGO
      serves as a light-weight flexible platform to anchor the ferrocene molecules to
      prevent them from dissolving into the aprotic electrolyte.

PMID- 21845269
TI  - Template-free solvothermal synthesis of yolk-shell V2O5 microspheres as cathode
      materials for Li-ion batteries.
AB  - Uniform yolk-shell V(2)O(5) microspheres were synthesized via a facile template
      free solvothermal route and subsequent calcination treatment in air. The
      resulting cathode materials showed a high specific capacity of 220 mA h g(-1)
      after 30 cycles and good rate capability.

PMID- 21845270
TI  - Formation of large 2D nanosheets via PVP-assisted assembly of anatase TiO2
      nanomosaics.
AB  - We demonstrate an unusual formation of large 2D nanosheets from nanomosaic
      building blocks of anatase TiO(2) nanosheets with exposed (001) facets. It is
      proposed that large PVP molecules adsorbed on the (001) facets serve as the
      linker that brings building blocks together, at the same time prevents them from
      stacking along the c-axis.

PMID- 21845271
TI  - Theoretical analysis of reaction kinetics with singlet oxygen molecules.
AB  - A comparative analysis of predictive ability of three approaches to estimate the
      rate constants of reactions of H(2), H, H(2)O and CH(4) with electronically
      excited O(2)(a(1)Delta(g)) and O(2)(b(1)Sigma(g)(+)) molecules is conducted. The
      first approach is based on a detailed ab initio study of potential energy
      surfaces. The second one is known as the "bond energy-bond order" method, and the
      third approach is a modification of the updated method of vibronic terms that
      makes it possible to evaluate the activation energy of reactions involving
      electronically excited species. The comparison showed that the estimates of the
      energy barrier by the updated method of vibronic terms for some reactions can be
      in good agreement with ab initio calculations and available experimental data. It
      was revealed that reactions of O(2)(b(1)Sigma(g)(+)) molecules with H(2), H(2)O
      and CH(4) molecules and with the H atom result in the formation of electronically
      excited species. The reactivity of O(2)(b(1)Sigma(g)(+)) molecules is smaller
      than that of O(2)(a(1)Delta(g)) ones, but much higher as compared to the
      reactivity of ground state O(2) molecules. For each reaction under study
      involving oxygen molecules in the excited electronic states O(2)(a(1)Delta(g))
      and O(2)(b(1)Sigma(g)(+)) the recommended temperature-dependent rate constants
      are presented.

PMID- 21845272
TI  - Influence of water-protein hydrogen bonding on the stability of Trp-cage
      miniprotein. A comparison between the TIP3P and TIP4P-Ew water models.
AB  - We report extensive replica exchange molecular dynamics (REMD) simulations on the
      folding/unfolding equilibrium of Trp-cage miniprotein using the Amber ff99SB all
      atom forcefield and TIP3P and TIP4P-Ew explicit water solvent models. REMD
      simulation-lengths in the 500 ns to the microsecond regime per replica are
      required to adequately sample the folding/unfolding equilibrium. We observe that
      this equilibrium is significantly affected by the choice of the water model.
      Compared with experimental data, simulations using the TIP3P solvent describe the
      stability of the Trp-cage quite realistically, providing a melting point which is
      just a few Kelvins above the experimental transition temperature of 317 K. The
      TIP4P-Ew model shifts the equilibrium towards the unfolded state and lowers the
      free energy of unfolding by about 3 kJ mol(-1) at 280 K, demonstrating the need
      to fine-tune the protein-forcefield depending on the chosen water model. We
      report evidence that the main difference between the two water models is mostly
      due to the different solvation of polar groups of the peptide. The unfolded state
      of the Trp-cage is stabilized by an increasing number of hydrogen bonds,
      destabilizing the alpha-helical part of the molecule and opening the R-D salt
      bridge. By reweighting the strength of solvent-peptide hydrogen bonds by adding a
      hydrogen bond square well potential, we can fully recover the effect of the
      different water models and estimate the shift in population as due to a
      difference in hydrogen bond-strength of about 0.4 kJ mol(-1) per hydrogen bond.

PMID- 21845273
TI  - Biaryl formation in the synthesis of endo and exo-platinacycles.
AB  - The reactions of cis-[Pt(2)(4-MeC(6)H(4))(4)(MU-SEt(2))(2)] with bifunctional
      ligands ArCH=NCH(2)(2-XC(6)H(4)) containing a C-X bond at the ortho positions of
      the benzyl ring (Ar = 4-ClC(6)H(4), X = Br (1d); Ar = 2,4,6-(CH(3))(3)C(6)H(2), X
      = Br (1e); Ar = 2,4,6-(CH(3))(3)C(6)H(2), X = Cl (1f); Ar = 2-CH(3)C(6)H(4), X =
      Br (1h); Ar = 2,6-F(2)C(6)H(3), X = Br (1i)) in refluxing toluene were studied.
      Several types of platinum(II) cyclometallated compounds containing a biaryl
      linkage were obtained: i) endo-five-membered with a Pt-C(sp(2)) bond (2d, 2h),
      ii) endo-six-membered with a Pt-C(sp(3)) bond (2e, 2f), and iii) exo-five
      membered with a Pt-C(sp(2)) bond (2i). The formed biaryl linkage involves the
      metallated ring for 2i and the non-metallated ring for the endo-metallacycles.
      The reaction of compounds 2 with PPh(3) produced the corresponding phosphine
      derivatives, some of which (3d, 3e, 3h and 3i) were characterised
      crystallographically. In addition, compound [PtBr{2
      CH(3)C(6)H(3)C(6)H(4)CH=NCH(2)(2-C(6)H(4)Br)}SEt(2)] (2c) containing a seven
      membered endo-metallacycle was also obtained and characterised
      crystallographically.

PMID- 21845274
TI  - Microfluidic baker's transformation device for three-dimensional rapid mixing.
AB  - We developed a new passive-type micromixer based on the baker's transformation
      and realized a fast mixing of a protein solution, which has lower diffusion
      constant. The baker's transformation is an ideal mixing method, but there is no
      report on the microfluidic baker's transformation (MBT), since it is required to
      fabricate the complicated three-dimensional (3D) structure to realize the MBT
      device. In this note, we successfully fabricate the MBT device by using precision
      diamond cutting of an oxygen-free copper substrate for the mould fabrication and
      PDMS replication. The MBT device with 10.4 mm mixing length enables us to achieve
      complete mixing of a FITC solution (D = 2.6 * 10(-10) m(2) s(-1)) within 51 ms
      and an IgG solution (D = 4.6 * 10(-11) m(2) s(-1)) within 306 ms. Its mixing
      speed is 70-fold higher for a FITC solution and 900-fold higher for an IgG
      solution than the mixing speed by the microchannel without MBT structures. The
      Peclet number to attain complete mixing in the MBT device is estimated to be 6.9
      * 10(4).

PMID- 21845275
TI  - A novel preparation of small TiO2 nanoparticle and its application to dye
      sensitized solar cells with binder-free paste at low temperature.
AB  - TiO(2) nanoparticles with diameter <10 nm were synthesized by a facile, non
      hydrothermal method at low temperature. A porous TiO(2) film electrode consisting
      of the obtained small TiO(2) nanoparticles and commercial TiO(2) nanoparticles
      without any organic binder was prepared at low temperature. The photovoltaic
      performance of the solar cell based on the TiO(2) electrode was investigated by
      the current-voltage and electrochemical impedance spectra. All the experimental
      results indicate that the addition amount of the small TiO(2) nanoparticles in
      the binder-free paste affects the photovoltaic performance of the photoelectrode
      greatly. The overall energy conversion efficiency of the optimized binder-free
      photoelectrode achieves 3.53% without high-temperature sintering. Additionally,
      the performance of the small particles derived from this facile method can be
      comparable with that of small ones obtained from traditionally hydrothermal
      method, indicating the small particles in our study can be applied to flexible
      dye-sensitized solar cells. And the present low-temperature preparation of
      photoelectrode containing small TiO(2) nanoparticles shows an encouraging
      performance on both conductive glass and plastic substrates and could be suited
      in the industrial and large-scale application due to its low energy cost and
      relatively high conversion efficiency.

PMID- 21845276
TI  - Carbon-based layer-by-layer nanostructures: from films to hollow capsules.
AB  - Over the past years, the layer-by-layer (LbL) assembly has been widely developed
      as one of the most powerful techniques to prepare multifunctional films with
      desired functions, structures and morphologies because of its versatility in the
      process steps in both material and substrate choices. Among various functional
      nanoscale objects, carbon-based nanomaterials, such as carbon nanotubes and
      graphene sheets, are promising candidates for emerging science and technology
      with their unique physical, chemical, and mechanical properties. In particular,
      carbon-based functional multilayer coatings based on the LbL assembly are
      currently being actively pursued as conducting electrodes, batteries, solar
      cells, supercapacitors, fuel cells and sensor applications. In this article, we
      give an overview on the use of carbon materials in nanostructured films and
      capsules prepared by the LbL assembly with the aim of unraveling the unique
      features and their applications of carbon multilayers prepared by the LbL
      assembly.

PMID- 21845277
TI  - Cationic polyfluorenes for intracellular delivery of proteins.
AB  - Two cationic polyfluorene derivatives, quaternary amine 1 and guanidine 2
      sheathed systems, were prepared as potential carriers to mediate import of
      proteins into cells without requiring covalent attachment to the protein. Neither
      polymer showed significant cytotoxicities (IC(50) 100 MUM) when exposed to Clone
      9 rat liver cells. Both polymers were shown to mediate import of a series of four
      proteins chosen because they have different pI values, sizes, and variable
      organic fluor attachments. Once inside the cells, the quaternary amine system 1
      released more of its cargo into regions outside the lysosomes. In one exploratory
      experiment, pyrenebutyrate was shown to accelerate import of a protein system by
      polymer 1.

PMID- 21845278
TI  - (S)-Lysine adsorption induces the formation of gold nanofingers on Au{111}.
AB  - STM imaging following the adsorption of (S)-lysine on Au{111} leads to the
      observation of Au nanofingers whose growth directions correlate with the unit
      cell vectors of ordered 2-D phases of lysine. The likely mechanism of surface
      restructuring is discussed.

PMID- 21845279
TI  - Syntheses of mGluR5 PET radioligands through the radiofluorination of
      diaryliodonium tosylates.
AB  - 3-Fluoro-1-((thiazol-4-yl)ethynyl)benzenes constitute an important class of high
      affinity metabotropic glutamate subtype 5 receptor (mGluR5) ligands, some of
      which have been labeled with fluorine-18 (t(1/2) = 109.7 min), to provide
      radioligands for molecular imaging of brain mGluR5 in living animal and human
      subjects with positron emission tomography (PET). Labeling in the 3-fluoro
      position of such ligands can be achieved through aromatic nucleophilic
      substitution of a halide leaving group with [(18)F]fluoride ion when a weakly
      activating m-nitrile group is present, but is generally very low yielding (<8%).
      Here we used a microfluidic reaction platform to show that greatly enhanced (up
      to 6-fold) radiochemical yields can be achieved from suitably synthesized
      diaryliodonium tosylate precursors. The presence of a m-nitrile or other
      activating group is not required. Similar conditions were adopted in a more
      conventional automated radiochemistry platform having a single-pot reactor, to
      produce mGluR5 radioligands with useful radioactivities for PET imaging.

PMID- 21845280
TI  - Flavonoids and their glycosides, including anthocyanins.

PMID- 21845281
TI  - Control of chemoselectivity in Dieckmann ring closures leading to tetramic acids.
AB  - An efficient strategy for the control of the chemoselectivity in Dieckmann ring
      closures leading to tetramic acids derived from serine and alpha-methyl serine is
      reported, and this provides pathways to diversely substituted systems from a
      common starting material.

PMID- 21845282
TI  - A DNA hybridization detection based on fluorescence resonance energy transfer
      between dye-doped core-shell silica nanoparticles and gold nanoparticles.
AB  - A novel and efficient method to evaluate the DNA hybridization based on a
      fluorescence resonance energy transfer (FRET) system, with fluorescein
      isothiocyanate (FITC)-doped fluorescent silica nanoparticles (SiNPs) as donor and
      gold nanoparticles (AuNPs) as acceptor, has been reported. The strategy for
      specific DNA sequence detecting is based on DNA hybridization event, which is
      detected via excitation of SiNPs-oligonucleotide conjugates and energy transfer
      to AuNPs-oligonucleotide conjugates. The proximity required for FRET arises when
      the SiNPs-oligonucleotide conjugates hybridize with partly complementary AuNPs
      oligonucleotide conjugates, resulting in the fluorescence quenching of donors,
      SiNPs-oligonucleotide conjugates, and the formation of a weakly fluorescent
      complex, SiNPs-dsDNA-AuNPs. Upon the addition of the target DNA sequence to SiNPs
      dsDNA-AuNPs complex, the fluorescence restores (turn-on). Based on the restored
      fluorescence, a homogeneous assay for the target DNA is proposed. Our results
      have shown that the linear range for target DNA detection is 0-35.0 nM with a
      detection limit (3sigma) of 3.0 picomole. Compared with FITC-dsDNA-AuNPs probe
      system, the sensitivity of the proposed probe system for target DNA detection is
      increased by a factor of 3.4-fold.

PMID- 21845283
TI  - Chemical vapour deposition of In2O3 thin films from a tris-guanidinate indium
      precursor.
AB  - A new homoleptic sublimable indium(III) guanidinate, (In[(N(i)Pr)(2)CNMe(2)](3)
      (1), was synthesized from a facile high-yield procedure. Compound 1 crystallized
      is a P1 space group; a = 10.5989(14) A, b = 11.0030(15) A, c = 16.273(2) A, alpha
      = 91.190(2) degrees , beta = 96.561(2) degrees , gamma = 115.555(2) degrees ; R =
      3.50%. Thermogravimetric analysis showed 1 to produce elemental indium as a
      residual mass. Thermolysis in a sealed NMR tube showed carbodiimide and
      protonated dimethyl amine by (1)H NMR. Chemical vapour deposition experiments
      above 275  degrees C with air as the reactant gas showed 1 to readily deposit
      cubic indium oxide with good transparency.

PMID- 21845284
TI  - The transition from a molecular to a continuum solvent in electrical double
      layers showing ion-ion correlation effects.
AB  - We analyze, using Monte Carlo simulations, how a dielectric medium, modeled as a
      Stockmayer fluid, modulates the force between two similarly charged surfaces. A
      major objective is to provide a basis for understanding the strengths and
      weaknesses of the primitive model. The system studied has uniformly charged walls
      separated by counterions and solvent, where the latter is kept at constant
      chemical potential as the separation between the walls is varied. For two
      different types of Stockmayer fluids, one with a "low" (epsilon(r) ? 4.4) and one
      with a "high" (epsilon(r) ? 20) relative dielectric permittivity, the size of the
      solvent molecules is varied systematically. As the size of the solvent molecules
      becomes smaller one approaches the continuum limit, where the primitive model
      should give an increasingly more accurate representation. We find that having an
      explicit description of the solvent gives rise to an oscillatory component in the
      force between the surfaces. The wavelength of the oscillations reflects the
      diameter of the solvent molecules. The smaller the solvent molecules the smaller
      are the amplitudes of the oscillations. On integrating the force curves to yield
      interaction free energies the oscillatory features become less apparent. For the
      smallest solvent size studied the interaction curves show clear similarities with
      those obtained from the primitive model. The qualitative effect of the dielectric
      screening is recovered. It is found that the deviations from the mean field
      description also appear for the molecular solvent. All this suggests that there
      are no major deviations due to the neglect of many-body contributions in the
      solvent-averaged potential of the primitive model. This also holds for the
      incompressibility assumption implicitly applied when using the primitive model.

PMID- 21845285
TI  - Halogen bonding or close packing? Examining the structural landscape in a series
      of Cu(II)-acac complexes.
AB  - A series of four bifunctional ligands based on beta-diketonate moieties bearing
      methyl (2), chloro (3), bromo (4) and iodo (5) substituents and their
      corresponding Cu(II) complexes have been synthesized and crystallographically
      characterized in order to explore the possibility of using halogen bonds for the
      directed assembly of predictable architectures in coordination chemistry. The
      four ligands have characteristic O-H...O intramolecular hydrogen bonds and the
      structure of ligand 2 is close packed whereas, ligands 3, 4 and 5 contain
      extended 1-D architectures based on C=O...X halogen bonds. In each case, the
      halogen-bond donor seeks out the most powerful halogen-bond acceptor (based on
      electrostatic considerations). In the corresponding Cu(II) complexes the
      coordination chemistry remains a constant throughout the series, the four
      coordinate metal ion sits in a slightly distorted square-planar arrangement, and
      there are no unexpected appearances of coordinated or non-coordinated solvent
      molecules. Furthermore, the most powerful halogen-bond acceptors have been almost
      depleted of charge as a result of metal chelation and none of the potential
      halogen-bond interactions are capable of competing with the head-to-head close
      packing that is observed in the methyl, chloro, and bromo, substituted Cu(II)
      complexes. The enhanced polarizability of the iodine atom, produces a more
      electropositive surface which means that this structure cannot accommodate a
      linear head-to-head arrangement due to electrostatic repulsion, and thus
      [Cu(5)(2)] adopts a unique close-packed structure very different from the other
      three iso-structural complexes, [Cu(2)(2)]-[Cu(4)(2)].

PMID- 21845286
TI  - A model-driven privacy compliance decision support for medical data sharing in
      Europe.
AB  - OBJECTIVES: Clinical practitioners and medical researchers often have to share
      health data with other colleagues across Europe. Privacy compliance in this
      context is very important but challenging. Automated privacy guidelines are a
      practical way of increasing users' awareness of privacy obligations and help
      eliminating unintentional breaches of privacy. In this paper we present an
      ontology-plus-rules based approach to privacy decision support for the sharing of
      patient data across European platforms. METHODS: We use ontologies to model the
      required domain and context information about data sharing and privacy
      requirements. In addition, we use a set of Semantic Web Rule Language rules to
      reason about legal privacy requirements that are applicable to a specific context
      of data disclosure. We make the complete set invocable through the use of a
      semantic web application acting as an interactive privacy guideline system can
      then invoke the full model in order to provide decision support. RESULTS: When
      asked, the system will generate privacy reports applicable to a specific case of
      data disclosure described by the user. Also reports showing guidelines per Member
      State may be obtained. CONCLUSION: The advantage of this approach lies in the
      expressiveness and extensibility of the modelling and inference languages adopted
      and the ability they confer to reason with complex requirements interpreted from
      high level regulations. However, the system cannot at this stage fully simulate
      the role of an ethics committee or review board.

PMID- 21845287
TI  - Health IT in Asia-Pacific region.
AB  - APAMI 2009 was held in Hiroshima, Japan, on November 22-24, 2009. This issue
      includes two selected papers recommended by the programming committee co-chairs.
      They are "Lessons Learned from Data Mining of WHO Mortality Database" and "Survey
      on Medical Records and EHR in Asia-Pacific Region - Languages, Purposes, IDs and
      Regulations". The theme of APAMI 2009 was "What are the medical records for?" A
      Hiroshima episode; Medical Records at Dr. Ban's Clinic, 9 km from the Epicenter
      of A-Bomb, is included, which lets us think of the fundamental purpose of medical
      records.

PMID- 21845288
TI  - How can eHealth help fix broken health systems?

PMID- 21845289
TI  - Effect of a participatory educational program on primary school teachers'
      knowledge of malaria.
AB  - OBJECTIVE: To describe a participatory educational program for building up
      knowledge on malaria among primary school teachers in a highly endemic city.
      METHODS: An observational study was conducted. A 40-hour course with a
      multidisciplinary and problematizing approach was held in 2008, including 46
      teachers mainly from rural areas of the city of Barcelos, Northern Brazil. The
      participatory educational process was comprised of workshops and practical
      classes. A previously validated questionnaire was applied before and after the
      course to assess teachers' knowledge and subsequently analyzed using qualitative
      and quantitative approaches and open-response thematic analysis. RESULTS: Prior
      to the course, teachers had little information about the transmission mechanisms,
      means of prevention, and the association between malaria and its vectors, and
      their health concepts were limited. After the course, teachers' knowledge of
      malaria increased and they reflected on their role in society. CONCLUSIONS: The
      effect of the educational program on the construction of contextualized knowledge
      of malaria and health indicates the potential of the strategy developed.
      Continuing education processes are required for the maintenance of new knowledge
      and practices directed towards health promotion.

PMID- 21845290
TI  - Quality of information registered on fetal deaths certificates in Sao Paulo,
      Southeastern Brazil.
AB  - OBJECTIVE: To evaluate the quality of information registered on fetal death
      certificates. METHODS: Records were reviewed from 710 fetal deaths registered in
      the consolidated database of deaths from the State System for Data Analysis and
      the Sao Paulo State Secretary of Health, for deaths in Sao Paulo municipality
      (Southeastern Brazil) during the first semester of 2008. Completeness was
      analyzed for variables on fetal death certificates issued by hospitals and
      autopsy service. The death certificates from a sub-sample of 212 fetal deaths in
      hospitals of the National Unified Health System (public) were compared to medical
      records and to the records from Coroners Office. RESULTS: Among death
      certificates, 75% were issues by Coroners Office, with a greater frequency in
      public hospitals (78%). Completeness of variables on death certificates issued by
      hospitals was higher among non-public hospitals. There was greater completeness,
      agreement and sensitivity in death certificates issued by hospitals. There was
      low agreement and high specificity for variables related to maternal
      characteristics. Increased reporting of gender, birth weight and gestational age
      was observed in certificates issued by Coroners Office. Autopsies did not result
      in improved ascertainment of cause of death, with 65.7% identified as unspecified
      fetal death as 24.3% as intrauterine hypoxia, while death certificates by
      hospitals reported 18.1% as unspecified and 41.7% as intrauterine hypoxia.
      CONCLUSIONS: Completeness and the ascertainment of cause of fetal death need to
      be improved. The high proportion of autopsies did not improve information and
      ascertainment of cause of death. The quality of information generated by
      autopsies depends on access to hospital records.

PMID- 21845291
TI  - Sleep, stress and compensatory behaviors in Australian nurses and midwives.
AB  - OBJECTIVE: To describe sleep, stress and compensatory behaviors in nurses and
      midwives. METHODS: The study included 41 midwives and 21 nurses working in
      Australian hospitals between 2005 and 2009. Participation was voluntary. All
      participants recorded on a daily basis their work and sleep hours, levels of
      stress and exhaustion, caffeine intake and use of sleep aids for a month (1,736
      days, 1,002 work shifts). RESULTS: Participants reported moderate to high levels
      of stress and exhaustion on 20-40% of work days; experienced sleep disruption on
      more than 50% of work days; struggled to remain awake on 27% of work days; and
      suffered extreme drowsiness or experienced a near accident while travelling home
      on 9% of workdays. Age, perceived sleep duration and work hours were significant
      predictors of caffeine intake. About 60% of participants reported using sleep
      aids (about 20% reported taking prescription medications and 44% of nurses and 9%
      of midwives reported alcohol use as a sleep aid at least once during the study).
      Stress and workdays were significant predictors of sedative use. Overall, 22%
      reported being indifferent or mildly dissatisfied with their job. CONCLUSIONS:
      Sleep problems, high levels of stress and exhaustion and low job satisfaction are
      prevalent among nurses and midwives. The use of alcohol and sleeping pills as
      sleep aids, and the use of caffeine to help maintain alertness is also common.
      Nurses and midwives may use caffeine to compensate for reduced sleep, especially
      on workdays, and sleeping pills to cope with their daily work-related stress.

PMID- 21845292
TI  - Early detection of cervical cancer according to the discourses of primary care
      midwives in Segovia, Spain.
AB  - OBJECTIVE: To analyze the discourses of primary care midwives on access to and
      utilization of the Cervical Cancer Prevention Program. METHODS: A qualitative
      study was conducted in an area of low population density with a high proportion
      of rural population in Segovia, Spain, between 2008 and 2009. Semi-structured
      interviews were carried out. Ten primary care midwives were interviewed covering
      the 16 basic health districts of the city. Data analysis was based on grounded
      theory methodology. RESULTS: Access to and utilization of the Cervical Cancer
      Prevention Program was associated with attendance to midwife visits, women's
      experiences with cervical smears and their perception of risk of cervical cancer.
      Geographic distance to the health center, difficult access to immigrant women who
      have no health insurance, and being unaware of the program offered are some of
      the perceived barriers. Social exclusion is also perceived as a barrier of access
      to and utilization of the program. The recommendation to participate in the
      program made by the primary care physician was identified as the main
      facilitator. CONCLUSIONS: The midwives perceived inequalities in access to and
      utilization of the Cervical Cancer Prevention Program that are associated to
      individual characteristics of women, and contextual characteristics such as the
      geographical environment where they live and Program's infrastructure. There is
      inequality of access to care of underrepresented groups of women such as
      immigrant women and those residing in rural areas.

PMID- 21845294
TI  - [Human resources for health].

PMID- 21845293
TI  - Edentulism and shortened dental arch in Brazilian elderly from the National
      Survey of Oral Health 2003.
AB  - OBJECTIVE: To describe the distribution of edentulism and estimate the prevalence
      of functional dentition and shortened dental arch among elderly population.
      METHODS: A population-based epidemiological study was carried out with a sample
      of 5,349 respondents aged 65 to 74 years obtained from the 2002 and 2003
      Brazilian Ministry of Health/Division of Oral Health survey database. The
      following variables were studied: gender; macroregion of residence; missing
      teeth; percentage that met the World Health Organization goal for oral health in
      the age group 65 to 74 years (50% having at least 20 natural teeth); presence of
      shortened dental arch; number of posterior occluding pairs of teeth. The Chi
      square test assessed the association between categorical variables. The Kruskal
      Wallis and Mann-Whitney tests were used to assess differences of mean between
      number of posterior occluding pairs teeth, macro-region and gender. RESULTS: The
      elderly population had an average of 5.49 teeth (SD: 7.93) with a median of 0.
      The proportion of completely edentulous respondents was 54.7%. Complete
      edentulism was 18.2% in the upper arch and 1.9% in the lower arch. The World
      Health Organization goal was achieved in 10% of all respondents studied. However,
      only 2.7% had acceptable masticatory function and aesthetics (having at least
      shortened dental arch) and a mean number of posterior occluding pairs of 6.94
      (SD=2.97). There were significant differences of the percentage of respondents
      that met the World Health Organization goal and presence of shortened dental arch
      between men and women. There were differences in shortened dental arch between
      macroregions. CONCLUSIONS: The Brazilian epidemiological oral health survey
      showed high rate of edentulism and low rate of shortened dental arch in the
      elderly population studied, thus suggesting significant functional and aesthetic
      impairment in all Brazilian macroregions especially among women.

PMID- 21845295
TI  - [National agenda for research in human resources for health: generating evidence
      for improving the health sector competences].

PMID- 21845296
TI  - [Supply and demand of medical specialists in the health facilities of the
      Ministry of Health: national, regional and by type of specialty gaps].
AB  - OBJECTIVES: To characterize the supply, demand and the gap of medical specialists
      in facilities of the Ministry of Health of Peru (MINSA) at the national, regional
      and specialty type levels. MATERIALS AND METHODS: Observational, descriptive
      study through which we calculated the supply of medical specialists using
      secondary sources of MINSA. The analysis of the demand for medical specialists
      was based on two methodologies: the need for specialists according to the
      guidelines of classification of the health facilities and according to the
      epidemiological and demographic profile. The arithmetic difference between the
      estimated demand and the supply was the procedure used to calculate the gap of
      medical specialists. RESULTS: The Ministry of Health has a total supply at the
      national level of 6,074 medical specialists of which 61.5% belong to the clinical
      specialties, 33.2% to the surgical specialties, 4.9% specialities related to aid
      to diagnosis and treatment and 0.4% to public health specialties. According to
      the categorization guideline there is a total demand of 11,176 medical
      specialists and according to the epidemiological and demographic profile of
      11,738. The national estimated gaps found are similar in both methods, although
      they differ widely across regions and by type of specialty. At the regional
      level, the gaps are greater in Loreto, Piura, Puno and Madre de Dios when
      estimating the defficit in relation to the supply. Regarding the speciality, the
      gap is greater in the four basic specialties: gynecology and obstetrics,
      pediatrics, internal medicine and general surgery. CONCLUSIONS: There is a waid
      gap between supply and demand of medical specialists at the national and regional
      levels, as a whole representing approximately 45% of the current offer,
      regardless of the estimation method.

PMID- 21845297
TI  - [Labor projection in the countryside and associated factors in newly collegiated
      physicians in Lima, Peru 2010].
AB  - OBJECTIVES: To estimate the prevalence and associated factors with the labor
      porjection in the countryside of physicians from Lima. MATERIALS AND METHODS: We
      conducted a cross-sectional study of 782 physicians who were surveyed during
      their affiliation at Peruvian Medical College during March and April 2010. Labor
      projection in the countryside was defined such as if they responded "inside the
      country" to the question "Where do you plan to be working in the next five
      years?" We used a multiple logistic regression model to find the associated
      factors. RESULTS: The average age of the participants was 25 years, 54% were
      female and 73% graduated in private universities. Only 7.0% reported plans to
      work in the countryside and 0,5% in rural areas. No association with gender,
      place of birth, having physicians in their family, university type, the english
      efficiency, having resided for more than a one year in the provinces and the year
      of completion of internship was found. In the multivariate analysis, we found
      association with having made the internship inside the country (OR: 3.1, 95%CI
      :1.5-6.3), communicate in Quechua (OR: 2.9, CI 1.4- 6.1), both parents born in
      the countryside (OR: 2.8, CI :1.4-5.6), while a monthly salary projection of more
      than $ 1780 dollars (OR: 0.4 CI :0.2-0,8) and living with their nuclear family or
      partner (OR: 0.3, CI :0.1-0.5) were negatively associated. CONCLUSIONS: Labor
      projection of work in the countryside of recently collegiated physicians from
      Lima is low. Some of the factors found can help to design strategies to reverse
      this situation.

PMID- 21845298
TI  - [Supply and demand of clinical practice fields for training undergraduate health
      sciences students in Peru, 2005-2009].
AB  - OBJECTIVES: To describe the supply and demand of clinical fields for
      undergraduate students of Peru. MATERIALS AND METHODS: A descriptive study was
      considering as supply of clinical fields the total number of existing hospital
      beds in Peru. The demand was calculated using the total number of alumni
      registered in health science carrers following the clinical years or the
      internship. We calculated the number of beds per student and the coverage of
      clinical fields nationally and in some selected regions (Lima, Arequipa, La
      Libertad and Lambayeque). RESULTS: In 2009, Peru had 34,539 hospital beds, 78.5%
      of which pertained to the public sector and 48.4% are from Lima. We estimated
      that in 2008 44,032 alumni needed clinical fields, 70% from private universities,
      which grew 65% since 2005. The coverage of clinical fields, considering only
      interns from four carreers (medicine, nursery, obstetrics and dentistry) was only
      31.5% at the national level. The number of beds per student oscillated between
      0.5 in La Libertad to 0.82 in Lima with a national mean of 0.45. CONCLUSIONS: The
      supply of clinical fields for teaching undergraduates is insufficient to satisfy
      the demand, which continues to grow because of private universities, and hence
      requires urgent regulation.

PMID- 21845299
TI  - [Level of knowledge in medical emergencies among medical students of Peruvian
      universities].
AB  - OBJECTIVES: The aim of this study was to evaluate the knowledge about medical
      emergencies of medical students from eleven Peruvian universities. MATERIALS AND
      METHODS: Multicenter, cross-sectional study, conducted between 2007- 2008. We
      used a nominal response, self-administered questionnaire with socio-educational
      questions and ten multiple choice questions on medical emergencies. We obtained a
      nonrandom sample of participants enrolled in universities. We obtained the chi2,
      crude and adjusted ORs with 95% confidence intervals and ulterior multivariate
      analysis. RESULTS: 2,109 medical students participated, the average age was 21
      years (range: 15-32), 51% were males. 53% had taken a previous course related to
      medical emergencies. 60.4% failed the questionnaire, the average score was 4.95
      over a maximum of 10 points and 5.9% obtained between 8-10 points. We found a
      strong association between the university of origin (OR: 0.45, 95% CI 0.38 to
      0.54), the academic stage (OR: 1.55, 95% CI 1.28 to 1.87), when they received the
      course about subject (OR: 0.62, 95% CI 0.50-0.77) and gender (OR: 1.38, 95% CI
      1.15 to 1.65). CONCLUSIONS: Knowledge of medical emergencies in the students of
      the eleven evaluated universities is not good, and we suggest the need of
      evaluating and improving the practical training offered by universities on issues
      regarding the management of medical emergencies.

PMID- 21845300
TI  - [Design of the National Surveillance of Nutritional Indicators (MONIN), Peru 2007
      2010].
AB  - OBJECTIVES: To describe the design and methods of the national surveillance of
      nutritional indicators (MONIN) 2007-2010, carried out by INS/CENAN. MATERIALS AND
      METHODS: MONIN was designed as a continuous (repeated cross-sectional) survey,
      with stratified multi-stage random sampling, considering the universe as all
      under five children and pregnant women residing in Peru, divided into 5
      geographical strata and 6 trimesters (randomly permuted weeks, about 78% of the
      time between November 19, 2007 and April 2, 2010). RESULTS: The total sample was
      3,827 children in 361 completed clusters. The dropout rate was 8.4% in clusters,
      1.8% in houses, and 13.2% in households. Dropout was also 4.2, 13.3, 21.2, 55%
      and 29% in anthropometry, hemoglobin, food intake, retinol and ioduria
      measurements, respectively. CONCLUSIONS: The MONIN design is feasible and useful
      for the estimation of indicators of childhood malnutrition.

PMID- 21845301
TI  - [Prevalence of overwight and obesity among children under five years in Peru 2007
      2010].
AB  - OBJECTIVES: To estimate the prevalence of overweight and obesity in children
      under five in Peru in the years 2007-2010 and to describe according to
      geographical areas, poverty levels, maternal education, breastfeeding, child age,
      sex and birth weight. MATERIALS AND METHODS: continuous (repeated cross
      sectional) multistage, random sampling survey from the universe of children under
      five-years and pregnant women living in Peru, divided into five geographical
      areas. RESULTS: Out of 3,669 children, 50.3% were males (Lima N=680, Remaining
      Coast N=763, Urban Sierra N=719, Rural Sierra N=699, Jungle N=808) having their
      weight and height measured according to international standards. The national
      prevalence of overweight and obesity was 6.9%, with Metropolitan Lima (10.1%) as
      the highest and in the Jungle (2.6%) as the lowest. Age, sex, geographical area
      and birth weight were identified as risk factors through multiple logistic
      regression. CONCLUSIONS: overweight and obesity are higher in Lima, during the
      first year of age and when birth weight is more than 2.5 Kg.

PMID- 21845302
TI  - [Long-lasting insecticide - treated bednet ownership, retention and usage one
      year after their distribution in Loreto, Peru].
AB  - OBJECTIVES: To assess long-lasting insecticide - treated bednet (LLITN)
      ownership, retention and usage one year after their distribution in Loreto, Peru.
      MATERIALS AND METHODS: From July to September 2007, 26,185 LLITNs Olyset Net (r)
      were delivered in 194 targeted communities in the Peruvian Amazon region,
      covering 45,331 people. Two cross-sectional community-based surveys in December
      2007 and July 2008 were undertaken in a sample of 60 targeted communities (30.9%
      out of the total). A semi-structured questionnaire was used to collect necessary
      data to calculate LLITN ownership, retention and usage indicators. RESULTS: High
      LLITN household ownership was showed in both surveys (99.9% and 98.7%,
      respectively). LLITN/ person ratio decreased from 0.58 at the end of the LLITN
      delivery to 0.51 in the second survey, estimating LLITN retention of 87% after 1
      year of intervention. In the first survey, 99.0% of all children <5 years and
      96,0% of pregnant women slept under a LLITN the previous night, while in the
      second survey, 77.7% of children <5 years and 66.3% of pregnant women slept under
      a LLITN the previous night. Big mesh size of LLITN had low people's
      acceptability, reaching only 39.0% in the second survey. CONCLUSIONS: Although
      universal LLITN household ownership remained high, their LLITN usage levels have
      decreased during one-year follow-up period.

PMID- 21845303
TI  - [Study of marine actinomycetes isolated from the central coast of Peru and their
      antibacterial activity against methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant Enterococcus faecalis].
AB  - OBJECTIVES: To determine the antimicrobial potential of marine actinomycetes
      against drug-resistant pathogens represented by strains of methicillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis
      (VRE). MATERIALS AND METHODS: Strains of actinomycetes (29) isolated from marine
      sediment were evaluated by their characteristics in two culture media and by
      testing their inhibitory capacity by in vitro antagonism against multi-drug
      resistant (MDR) pathogenic bacteria for MRSA and VRE. Organic extracts of 3
      selected actinomicetes were processed to determine the minimum inhibitory
      concentration (MIC) of the active compound. RESULTS: Most isolated actinomycetes
      belong to a homogeneous group of write-gray actinomycetes with a good growth in
      Marine Agar. The inhibitory rates of the isolates were above 85% for both
      pathogens with inhibition zones greater than 69 and 78 mm in diameter for MRSA
      and VRE respectively. Dichloromethane extracts of 3 isolates (I-400A, B1-T61, M10
      77) showed strong inhibitory activity of both pathogens, M10-77 being the highest
      actinomycete strain with antibiotic activity against methicillin-resistant S.
      aureus ATCC 43300 and vancomycin-resistant E. faecalis ATCC 51299 with a minimum
      inhibitory concentrations (MIC) of 7.9 and 31.7 MUg/ml respectively. Phylogenetic
      analysis of M10-77 strain showed 99% similarity with the marine species
      Streptomyces erythrogriseus. CONCLUSIONS: Marine sediments of the central coast
      of Peru, are a source of actinomycetes strains showing high capacity to produce
      bioactive compounds able to inhibit pathogens classified as multi-drug-resistant
      such as methicillin-resistant S. aureus and vancomycin-resistant E. faecalis.

PMID- 21845304
TI  - [Cardiovascular risk factors and apolipoproteic profile in a group of adults
      treated in a public health center in Carabobo state, Venezuela].
AB  - OBJECTIVES: To compare serum levels of apolipoproteins A-I and B as well as Apo
      B/Apo A-I and HDL cholesterol/Apo A-I ratios by age, gender and cardiovascular
      risk factors in individuals treated at a Venezuelan public health center.
      MATERIALS AND METHODS: We determined in 221 individuals (44.0 +/- 15.5 years) of
      both genders blood pressure, waist circumference (WC), lipid profile and
      apolipoproteins A-I and B; body mass index (BMI) was calculated from weight and
      height; smoking habit, alcohol intake and consumption pattern were established.
      RESULTS: 27.5% of individuals had low levels of Apo A-I, 45.2% high Apo B and
      60.6% high Apo B/Apo A-I ratio. Serum levels of apolipoproteins and Apo B/Apo A-I
      ratio did not vary with age or gender, while the ratio HDL cholesterol/Apo A-I
      decreased with the age. Obese individuals, smokers, hypertensive,
      hypercholesterolemics, hypertriglyceridemics or with low HDL cholesterol showed
      higher Apo B and Apo B/Apo A-I ratio. Older individuals, smokers or individuals
      with increased LDL cholesterol and triglycerides showed lower HDL cholesterol/Apo
      A-I ratio. Consumption of three or more alcoholic drinks/day was associated with
      decreased Apo B. CONCLUSIONS: These results show high prevalence of altered
      apolipoprotein profile, which is associated with major cardiovascular risk
      factors. The results support the inclusion of the evaluated apolipoproteins in
      laboratory determinations made in public health centers in Venezuela.

PMID- 21845305
TI  - [Diagnosis of drug-related problems in elderly patients at the time of
      hospitalization].
AB  - OBJECTIVES: To diagnose drug-related problems (DRPs) in patients over 64 years of
      age at the time of hospitalization. MATERIALS AND METHODS: The detection of
      overprescription and misprescription of medications was done using the Index of
      Appropriate Drug Use, and for underprescription the Indication of Adequate Drug
      Use in Vulnerable Elderly Adults and the test of the Evaluation of the Underuse
      of Drugs were used. The evaluation of drug adherence and adverse drug reactions
      was completed using the Morisky-Green Questionnaire and the Karch and Lasgna
      Algorithm, respectively. RESULTS: The study was conducted in 100 inpatients in a
      geriatric service in a multi-specialty hospital in Lima, Peru; the median age was
      76.26 +/- 6.91 and 55% were males. After evaluating 555 drugs with the Index of
      Appropriate Drug Use, 254 of them (45.8%) qualified for at least one or more of
      the criteria studied for inadequate prescription, corresponding to 89 of the
      studied patients. We found the underuse (21%) of Warfarin or aspirin by eligible
      patients with auricular fibrillation, and no use (59%) of beta blockers by
      patients with a history of acute myocardial infarction. The non-adherence and
      frequency of adverse reactions that motivated hospitalization were 63% and 24%,
      respectively. CONCLUSIONS: The diagnosis of DRPs in elderly adults at the time of
      hospitalization using valid instruments is extremely useful and should be part of
      the integral geriatric evaluation of the elderly.

PMID- 21845306
TI  - [Atorvastatin induced increase in homologous angiotensin I converting enzyme
      (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular
      hypertrophy in a rat model of diabetic cardiomyopathy].
AB  - OBJECTIVES: This study has investigated the effect of atorvastatin on the
      progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium
      in rats. MATERIALS AND METHODS: Diabetes was induced in Holtzman rats with an
      intraperitoneal injection of streptozotocin. The animals were divided into 3
      groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated
      orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the
      hearts were removed for morphometric studies, collagen content assay and genetic
      expressions of ACE and ACE2 mRNA. RESULTS: Myocardial hypertrophy index and
      collagen deposition were increased in diabetic rats, but not in the treated
      diabetic rats, without producing changes in cholesterol levels. Myocardial ACE
      mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic
      rats. Atorvastatin administration attenuated overexpression of ACE mRNA and
      overexpression of ACE-2 mRNA in diabetic rats. CONCLUSIONS: Our results indicate
      that atorvastatin, independently of its cholesterol-lowering capacity, lowers the
      ACE/ACE2 ratio to normal values and attenuates the development of adverse
      remodeling in the diabetic heart.

PMID- 21845307
TI  - [Seroprevalence of leptospirosis in Puente Piedra, Lima, in 2006].
AB  - Leptospirosis is a disease widely prevalent in tropical areas, but may also be
      present in urban areas. The present study aims to determine the seroprevalence of
      Leptospira in the district of Puente Piedra, where there have been cases of
      severe leptospirosis in recent years. We collected data related to risk factors
      associated with leptospirosis and blood samples from 250 participants, selected
      by random sampling. We found a high prevalence of risk factors in the population
      and using the microscopic agglutination test, antibodies were found in only 3
      participants (1.2%).

PMID- 21845308
TI  - [Mental health in physicians doing the rural and suburban health service in Peru:
      a baseline study].
AB  - The disadvantageous conditions in which young physicians have to do their rural
      and sub-urban health service (SERUMS) may put them in a high risk for mental
      disorders. This study aims to establish the baseline levels of depression and
      alcohol use problems among those physicians scheduled to complete their SERUMS
      during the period 2011-2012. The Center for Epidemiologic Studies Depression
      Scale (CES-D) and the Alcohol Use Disorders Identification Test (AUDIT) were
      administered as screening tests to 493 physicians. Depression scores were met by
      26% females and 14.5% males, and alcohol use problem scores were met by 22%
      females and 26% males. Overall, 39% persons scored for either of both mental
      health entities. Mental health problems seem to be common among young physicians
      scheduled to migrate to their SERUMS. These problems must be addressed to avoid
      greater risks.

PMID- 21845309
TI  - [Tuberculous spondylitis in adults: a case series from a reference hospital in
      Lima, Peru].
AB  - We describe the demographic and clinical characteristics of adult patients with
      tuberculous spondylitis as well as an exploratory analysis that seeked to
      establish patient characteristics that contributed to the development of this
      disorder at a reference hospital in Lima. This is a case-series descriptive study
      where data collection from 33 medical records of patients from 1999 to 2009 was
      done. Eighteen (55%) were male. Median age was 31 years (IQR 23 to 51 years).
      Median time of symptoms was 3 months (IQR 1 to 8 months). The most frequent
      symptom was back pain in 28 (85%). The most frequently affected areas were the
      thoracic spine involved in 28 (60%) cases and lumbar spine in 13 (28%). Pulmonary
      tuberculosis was present in fourteen (42%) cases. Twenty four (73%) patients
      received first line treatment. Treatment duration was 10.5 +/- 4.2 months.
      Clinical and diagnostic characteristics were similar to previous Peruvian case
      reports and current literature.

PMID- 21845310
TI  - [Translational research and its contribution to the decision making process in
      health policies].
AB  - Recently, the translational research model (TR) has been established as a key
      feature in health worldwide. The objectives of this review are: (1) to define the
      TR and describe its complex nature; (2) to identify the components of the TR; (3)
      to link the TR to the decision-making process in health policies; (4) to
      recognize frequent obstacles and challenges of the association between the TR and
      the decision-making process in health policies. A systematic literature review
      was conducted in scientific databases and selected grey literature was done
      including TR and health policy as key words. We found 60 papers. Results show
      that the concept of TR and its theoretical formulation has evolved over time and
      has only recently incorporated the complexity that exists in the transference of
      scientific knowledge to health. International literature shows different
      applications of the TR in both research and clinical practice. The application of
      the TR to public health and health policy decision making is relatively new but
      necessary and could become a priority for health policies in the countries.

PMID- 21845311
TI  - Global Health Workforce Alliance: increasing the momentum for health workforce
      development.
AB  - The Global Health Workforce Alliance was launched in 2006 to provide a joint
      platform for governments, development partners, international agencies, civil
      society organizations, academia, private sector, professional associations, and
      other stakeholders to work together to address a global crisis in human resources
      for health. Five years later the vision and mandate of the Alliance still remain
      valid. Despite advances in bringing the health workforce to the fore in
      international health policy arenas, more available knowledge and tools, and
      encouraging signs of commitments from many countries, health workforce
      bottlenecks continue to prevent many health systems from delivering essential and
      quality health services. Latin America is not spared from the challenges. The
      2010 Second Global Forum on Human Resources for Health provided an opportunity to
      review progress, identify persisting gaps, reach consensus on solutions, and
      renew the momentum for and commitment to acutely needed investment and actions.

PMID- 21845313
TI  - Overcoming the hurdle of implementation: putting human resources for health tools
      into action.
AB  - The global human resources for health (HRH) challenge remains persistent. In
      2006, the World Health Report identified 57 crisis countries, and, despite
      increased attention and investment in strengthening the workforce, those
      countries are still in crisis. While chronic HRH problems still exist, progress
      has been made in some countries where innovative programs have been implemented
      that show promise, or specific initiatives have been scaled up. Yet, these have
      not been substantive enough to move countries out of the "crisis" category. While
      many countries have HRH plans, this paper asserts that a major reason countries
      remain in crisis is the lack of sustained implementation to achieve concrete
      workforce strengthening results. This is true despite the fact that there have
      been major investments in a broad range of tools and resources aimed to support
      implementation of plans and initiatives.Given this picture, the paper states that
      it is critical for HRH leaders to take action to ensure that already available
      tools are disseminated, adapted and used to foster effective implementation at
      the country level. The paper highlights four such tools as examples that can be
      used to build implementation capacity, and acknowledges more like them. Having
      highlighted these tools, the paper concludes by offering recommendations as to
      how to support more results-oriented implementation. These recommendations are
      organized around three linked components: 1) providing sufficient advocacy to
      leadership at the national level to mobilize and commit them to implementation
      action, 2) assembling and managing the requisite assets (including the
      institutional arrangements, people and money) into a coherent and powerful whole,
      and 3) using accountability as a foundational tool to assess progress in
      implementation, track key indicators, celebrate achieving key milestones and
      identify problems when indicators are not achieved.

PMID- 21845312
TI  - Mid-level health providers: a promising resource.
AB  - Mid-level health providers (MLP) are health workers trained at a higher education
      institution for at least a total of 2-3 years, and authorized and regulated to
      work autonomously to diagnose, manage and treat illness, disease and impairments,
      as well as engage in preventive and promotive care. Their role has been
      progressively expanding and receiving attention, in particular in low- and middle
      income countries, as a strategy to overcome health workforce challenges and
      improve access to essential health services and achieve the health related
      targets of the Millennium Development Goals. Evidence, although limited and
      imperfect, shows that, where MLP are adequately trained, supported and integrated
      coherently in the health system, they have the potential to improve distribution
      of health workers and enhance equitable access to health services, while
      retaining quality standards comparable to, if not exceeding, those of services
      provided by physicians. Significant challenges however exist in terms of the
      marginalization and more limited management support of MLP in health systems. The
      expansion of MLP should have priority among the policy options considered by
      countries facing shortage and maldistribution challenges. Improved education,
      supervision, management and regulation practices and integration in the health
      system have the potential to maximize the benefits from the use of these cadres.

PMID- 21845314
TI  - Strategies for increasing the impact of research on human resources for health
      policy development.
AB  - Despite global recognition of the importance of human resources for health (HRH)
      in achieving health system goals, very little is known about what works, for whom
      and under what circumstances, especially for low-income and middle-income
      countries. Several important events and reports have called for increased funding
      and capacity for HRH research in recent years and several initiatives have
      started as a result. Progress has been slow, however. The following strategies
      can be most valuable in ensuring the relevance of the generated evidence for
      decision making and its contribution to stronger health systems. The first is to
      promote national processes to set priorities for HRH research with active
      participation from decision makers. The second is to make conscious efforts to
      scale up primary research to address priority questions and to develop
      sustainable mechanisms to evaluate the impact of current or new HRH strategies to
      feed into the policy making process. The third is to invest in the development of
      systematic reviews to synthesize available evidence and in the adaptation of the
      underlying methods to make them more responsive to the type of questions and the
      nature of research involving HRH issues. The fourth and most important is to
      consistently use a systems approach in framing and addressing research questions.
      While a narrow approach may be more attractive and simple, health systems and the
      problems facing them are not. Increasing the body of evidence that takes into
      account the complexity of health systems, and particularly human resources for
      health, will advance knowledge in this area and will make big strides in the
      quality and usefulness of the generated evidence.

PMID- 21845315
TI  - Addressing the Human Resources for Health crisis in countries: How far have we
      gone? What can we expect to achieve by 2015?
AB  - The World Health Report 2006 identified 57 countries world-wide whose health
      worker to population density fell below a critical threshold of 2.3 per 1,000
      population. This meant that below this critical threshold, a country could not
      provide the basic health services to its population, defined here as 80%
      immunization coverage and 80% skilled birth attendance at delivery. Of the 57
      countries, 36 are located in Africa. This article reviews the progress countries
      have made in addressing their health workforce crisis. It cites 3 of the most
      recent global studies and the indicators used to measure progress. It also
      features the experiences of 8 countries, namely Malawi, Peru, Ethiopia, Brazil,
      Thailand, Philippines, Zambia, Mali. Their situations provide a diverse picture
      of country efforts, challenges, and successes. The article asks the question of
      whether the target of 25% reduction in the number of crisis countries can be
      achieved by 2015. This was a goal set by the World Health Assembly in 2008. While
      the authors wish to remain optimistic about the striving towards this target,
      their optimism must be matched by an adequate level of investment in countries on
      HRH development. The next four years will show how much will really be achieved.

PMID- 21845316
TI  - [Health professionals for a new century: transforming education to strengthen
      health systems in an interdependent world].

PMID- 21845317
TI  - [Remunerations, benefits and labor incentives perceived by health care workers in
      Peru: an analysis comparing the Ministry of Health and the Social Insurance,
      2009].
AB  - OBJECTIVE: To describe the main characteristics of the general salaries situation
      and the incentive policies of health care workers of Peru, comparing them by
      their origin institution and type of contract. MATERIALS AND METHODS: A mixed
      design study was done including both quantitative and qualitative components
      during 2008 and 2009 with both professional and technical personnel of the
      Ministry of Health (MINSA) and the Social Insurance (EsSalud) in Peru. The salary
      structure was primarily evaluated considering incentives, bonuses and other
      remunerations according to position, type of contract and work place. RESULTS:
      Remuneration and bonus policies at the national level are determined by the
      responsibilities and amount of time served. The type of contract is determined by
      the programs of the public system (DL 276) and the private system (DL 728), also
      by the Special Program of Contract Services Administration (CAS) and exclusively
      in MINSA contracting is determined by local health administration Committees
      (CLAS). The salary structure differs between both types of institutions,
      especially with respect to incentives and benefits. An special economic incentive
      for assistance (AETA) is unique to MINSA, but the proportion of assistance varies
      by region. The professionals of MINSA have lower salaries than those of EsSalud,
      in all types of contracts. A professional contracted through CAS generally has a
      lower salary than staff peers in MINSA, though this situation is reversed in
      EsSalud. The lowest salaries are found in contracts made through CLAS.
      CONCLUSIONS: The structure and salary amounts differ between MINSA and EsSalud,
      just as they differ by existing contracting types.

PMID- 21845318
TI  - [Implementation of medical specialists brigades in the areas of Universal Health
      coverage: the Peruvian Ministry of Health experience, 2009-2010].
AB  - Peru has a high degree of inequity reflected in the distribution of morbidity and
      mortality, consistent with the inaccessibility to health care and human resource
      gap, especially in remote areas of the capital. The Peruvian Ministry of Health,
      recognizing the right of all people to quality health care, initiated the
      Universal Health Insurance (AUS), and in this context, increased access to
      specialized care in pilot AUS areas by brigades of specialist doctors. This
      article offers an approach to this strategy presents the management and
      implementation processes, a quantitative analysis with indicators of output /
      efficiency, and provides a qualitative look from the perspective of the members
      of the brigades. Its main findings reflect the lack of effective and efficient
      management, translated in the absence of: production goals, work plans, working
      partnerships with local stakeholders, monitoring and effective supervision,
      recurrent shortages of human and technological resources, and high costs.

PMID- 21845319
TI  - [Plansalud: Decentralized and agreed sector plan for the capacity development in
      health, Peru 2010-2014].
AB  - Human resources are the backbone of health sector actions; however, they are not
      necessarily the area with the greatest attention, therefore, the Ministry of
      Health of Peru (MINSA) together with regional governments, led the Decentralized
      and Agreed Sector Plan for the Capacity Development in Health 2010-2014
      (PLANSALUD) with the aim of strengthening the capacities of Human Resources for
      Health (HRH) and contribute to health care efficient development, quality,
      relevance, equity and multiculturalism, in the context of descentralization, the
      Universal Health Insurance (AUS) and health policies. To achieve this goal, they
      have proposed three components (technical assistance, joint training and
      education - health articulation) that bring together an important set of
      interventions, which are planned and defined according to the national, regional
      and local levels, thus contributing to improve the government capacity,
      capability management and delivery of health services. This paper presents a
      first approach of PLANSALUD, including aspects related to planning, management,
      financing, structure and functioning, as well as monitoring and evaluation
      measures.

PMID- 21845320
TI  - [Process of construction of the national research agenda on Human Resources in
      Health in Peru 2011 - 2014].
AB  - The National Health Authority of Peru, as part of the implementation of national
      priorities for health research in 2010 developed the process of building the
      national research agenda on health manpower (HM). In a scenario of technical
      challenges, national and international policy and under a nation-wide
      participatory approach with key stakeholders in the health system, training and
      aid HM linked to the subject, establishing a socially agreed agenda. Process
      consists of 3 phases: 1. National review of evidence and relevant information on
      RHUS, 2. Consultation with opinion leaders and subject experts, and 3. A
      collaborative space (national workshop) of deliberation, consensus and legitimacy
      of the agenda. Finally, we present the agenda consists of 30 research topics on
      health manpower, to be developed in the period 2011- 2014, and raises the
      challenges and prospects for implementation.

PMID- 21845321
TI  - [Interferon-induced autoimmune thyroiditis in a patient with hepatitis C virus
      infection].
AB  - A 43 year old man presented with asymptomatic elevation of alanine
      aminotransferase (ALT) and no relevant past history. The patient denied being a
      chronic alcohol drinker. Work-up revealed an active hepatitis C, and liver biopsy
      showed active inflammation. Treatment was started with interferon-alfa and
      ribavirin. During the 48 weeks of treatment, the patient developed positive
      thyroid antibodies with varying level of thyrotropin (TSH) and thyroid hormones.
      At follow-up after treatment, the patient continued with hyperthyroidism due to
      Graves' disease. Autoimmune thyroiditis is a common complication of using
      interferon in patients with hepatitis C. In some cases, it is presented as
      hyperthyroidism because of Graves' disease. Thyroid function and thyroid
      antibodies should be evaluated before and during treatment with interferon.

PMID- 21845324
TI  - [Intention in the way of getting the medical diploma among medical interns in
      Peru, 2010].

PMID- 21845325
TI  - [Why do effective interventions to improve childhood survival not reach those who
      most need them?].

PMID- 21845326
TI  - [Research: from hobby to job].

PMID- 21845327
TI  - [Hospital earthquake vulnerability: experiences from the Hospital Regional de Ica
      within four years from the disaster].

PMID- 21845328
TI  - [Childhood malnutrition in Peru: conditionant factors and trends].

PMID- 21845329
TI  - [Rethinking the education of XXI century health professionals: changes and
      actions in a global world].

PMID- 21845331
TI  - Incorporating Brazilian and Latin American perspectives in the ICD-11
      classification of mental and behavioral disorders.

PMID- 21845332
TI  - Gender-related issues in the diagnosis and classification of alcohol use
      disorders among Mexican patients seeking specialized services.
AB  - OBJECTIVE: The objective of the study was to examine the role of gender in the
      endorsement of symptoms included in both the International Classification of
      Diseases-10th Edition and the Diagnostic and Statistical Manual of Mental
      Disorders-4th Edition. METHOD: Six hundred patients treated for alcohol-related
      problems in outpatient services in Mexico were evaluated with the Substance Abuse
      Module of the Composite International Diagnostic Interview. RESULTS: Confirmatory
      factor analyses using the International Classification of Diseases-10th Edition
      and Diagnostic and Statistical Manual of Mental Disorders-4th Edition criteria
      produced two factors that included a combination of abuse/harmful alcohol use and
      dependence symptoms, which explained 40% and 49.2% of the total variance,
      respectively. In the abuse/harmful use groups of patients, symptoms and social
      consequences differed according to gender: withdrawal syndrome, lack of control
      and legal problems were more frequent in men, while women exhibited higher rates
      of attempts to give up alcohol and difficulties to accomplish daily activities.
      Specific gender-related factors differentiated abuse/harmful use from dependence,
      such as loss of control and time spent to drink in the case of men and desire to
      drink among women, according to the Diagnostic and Statistical Manual of Mental
      Disorders-4th Edition dependence criteria; and presence of physical symptoms in
      men and family/social problems, craving, and futile effort to stop drinking in
      women, according to the International Classification of Diseases-10th Edition
      dependence criteria. CONCLUSION: Future classification systems of substance abuse
      disorders should take into account differences between genders in order to help
      closing the treatment gap for women.

PMID- 21845333
TI  - Differential diagnosis between non-pathological psychotic and spiritual
      experiences and mental disorders: a contribution from Latin American studies to
      the ICD-11.
AB  - OBJECTIVE: To review research articles in psychiatry and psychology involving
      Latin American populations and/or produced by Latin American scholars to
      investigate the differential diagnosis between spiritual/anomalous experiences
      and mental disorders in order to contribute to the validity of the International
      Classification of Diseases towards its 11th edition in this area. METHOD: We
      searched electronic databases (PubMed, PsycINFO, Scopus, and SciELO) using
      relevant keywords (possession, trance, religious experience, spiritual
      experience, latin, Brazil) for articles with original psychiatric and
      psychological data on spiritual experiences. We also analyzed the references of
      the articles found and contacted authors for additional references and data.
      RESULTS: There is strong evidence that psychotic and anomalous experiences are
      frequent in the general population and that most of them are not related to
      psychotic disorders. Often, spiritual experiences involve non-pathological
      dissociative and psychotic experiences. Although spiritual experiences are not
      usually related to mental disorders, they may cause transient distress and are
      commonly reported by psychotic patients. CONCLUSION: We propose some features
      that suggest the non-pathological nature of a spiritual experience: lack of
      suffering, lack of social or functional impairment, compatibility with the
      patient's cultural background and recognition by others, absence of psychiatric
      comorbidities, control over the experience, and personal growth over time.

PMID- 21845334
TI  - Melancholia in Latin American studies: a distinct mood disorder for the ICD-11.
AB  - OBJECTIVE: Melancholic depression is a lifetime diagnosis, typically with
      recurrent episodes. Melancholia, a syndrome with a long history and distinctive
      psychopathological features, is differentiated from major depression by the DSM
      IV specifiers and partly described in the International Classification of
      Diseases - 10th edition. Within the present classification, it is frequently seen
      in severely ill patients with major depression and bipolar disorder.
      Nevertheless, it has a distinctive psychopathology and biological homogeneity in
      clinical experience and laboratory test markers, and it is differentially
      responsive to specific treatment interventions according to international
      studies. The objective of this study is to review the literature published by
      Latin American authors about Melancholia. METHOD: We conducted a systematic
      search to identify scientific literature published by Latin American authors
      gathering information relevant to the revision of the classification of mental
      and behavioral disorders in patients with melancholic depression of the
      International Classification of Diseases - 10th edition. The review was
      specifically focused on literature from Brazil and Latin America in order to
      examine the specific Latin American contribution for the study of melancholia as
      a distinct entity. RESULTS AND CONCLUSION: Melancholia can be identified as a
      separate mood disorder with unique psychopathology and psychoneuroendocrinology,
      worthy of separate attention in the classification systems. We therefore suggest
      that melancholia be positioned as a distinct, identifiable mood disorder that
      requires specific treatment.

PMID- 21845335
TI  - The contribution of Latin American and Caribbean countries on culture bound
      syndromes studies for the ICD-10 revision: key findings from a working in
      progress.
AB  - OBJECTIVE: This review aims to verify the scientific evidences for the inclusion
      of culture bound syndromes in the International Classification of Diseases
      towards its 11th edition based on studies from Latin American and Caribbean
      countries. METHOD: Studies were identified in Medline, LILACS and EMBASE
      databases for the period between 1992 and 2008, and then classified according to
      the type of study, to the mental disorder, country and number of publications per
      year. RESULTS: 163 studies were selected and classified: 33 in MedlLne, 90 in
      EMBASE e 40 in LILACS. The percentage of culture bound-syndrome corresponded to
      9% in Medline, 12% in EMBASE e 2.5% in LILACS. Among fifteen studies on cultural
      bound syndromes, two were about "nervios and ataque de nervios", two about
      "susto", four about the relationship between religion beliefs, witchery, trance
      and mental disorders, one with a proposal for new diagnostic category, three
      about theoretic issues and three about the pathoplasty of mental disorders.
      CONCLUSION: The scarcity of studies on culture bound syndromes might be due to
      the indexation problems hindering the screening of studies; lack of interest on
      publishing such studies in indexed journals (publication bias) and due to
      difficulty to access them. There is no robust evidence identified among cross
      cultural studies to recommend changes for International Classification of
      Diseases-11th edition.

PMID- 21845336
TI  - Somatization in Latin America: a review of the classification of somatoform
      disorders, functional syndromes and medically unexplained symptoms.
AB  - OBJECTIVE: medically unexplained symptoms are common and associated with mental
      illness in various contexts. Previous studies show that Latin American
      populations are prone to somatization. Given the reformulation of the
      International Classification of Diseases towards its 11th edition the
      peculiarities of the population from this region of the world shall be taken into
      consideration. The objective of this study is to provide information on
      somatization in Latin American populations to help the decision making about
      medically unexplained symptoms diagnostic categories in the 11th edition of the
      International Classification of Diseases. METHOD: Extensive review of the
      academic production from 1995 to 2011 on somatization in populations of Latin
      American origin. RESULTS: The analysis of 106 studies included in this review was
      divided into 15 categories: systematic reviews, conceptual reviews, prevalence,
      primary care, depression and anxiety, risk factors, violence, organic conditions,
      relationship with health care, ethnicity, culture-bound syndromes, chronic
      fatigue syndrome, fibromyalgia, body dysmorphic disorder, and conversion and
      dissociation. CONCLUSION: The Latin American studies confirm the difficulty in
      defining medically unexplained symptoms categories. The supposed "somatizing
      trace" of Latin cultures may be linked more to cultural and linguistic expression
      than to an ethnic nature, and these peculiarities must be on the agenda for the
      new classification of these phenomena in the Classification of Diseases-11th
      edition.

PMID- 21845337
TI  - A review of Latin American studies on binge eating disorder.
AB  - OBJECTIVE: To review the state of the art of the scientific literature on binge
      eating disorder in Latin America. METHOD: A literature search of studies
      conducted in Latin American countries using the term "binge eating" was performed
      in the following electronic databases: PubMed, LILACS, SciELO, and PsycINFO.
      Selected articles described studies developed with Latin American samples that
      met partial or complete DSM-IV diagnostic criteria for binge eating disorder.
      RESULTS: 8,123 articles were screened and 30 studies met the inclusion criteria
      (18 cross-sectional studies, 5 clinical trials, 4 case reports, 2 validity
      studies, and 1 cohort study). Most of the studies were conducted in Brazil (27),
      one in Argentina, one in Colombia, and one in Venezuela. The prevalence of binge
      eating disorder among obese people attending weight loss programs ranged between
      16% and 51.6%. The comparison between obese people with and without binge eating
      disorder showed a tendency of higher weight, longer history of weight
      fluctuation, more concern about shape and weight, and association with
      psychiatric comorbidity in those with binge eating disorder. CONCLUSION: Binge
      eating disorder is a detectable phenomenon in Latin America with clinical
      features similar to those found in the international literature. This review
      provides support for the consideration of binge eating disorder as a distinct
      eating disorder in the International Classification of Diseases - 11th edition.

PMID- 21845338
TI  - Effect of tamoxifen on the coronary vascular reactivity of spontaneously
      hypertensive female rats.
AB  - Tamoxifen has been associated with a reduction in the incidence of myocardial
      infarction. However, the effects of tamoxifen on coronary reactivity have not
      been fully elucidated. The objective of this study was to determine the effects
      of chronic treatment with tamoxifen on coronary vascular reactivity in
      spontaneously hypertensive rats (SHR). Female SHR were divided into four groups
      (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10
      mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized
      and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate
      (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were
      measured. MAP and HR were reduced (9.42 and 11.67%, respectively) in the
      OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular
      reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to
      acetylcholine (2-64 ug) when compared to the OVX group (P < 0.01) and this
      response was similar to that of the SHAM group. The adenosine-induced vasodilator
      response was greater in the TAMOX group compared to the SHAM and OVX groups (P <
      0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 +/- 3.6 and 130
      +/- 1.5 mmHg) than in OVX and SHAM groups (96 +/- 2 and 119 +/- 2.3 mmHg; P <
      0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced
      by acetylcholine and increased the adenosine-induced vasodilatory response, as
      well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on
      coronary vascular reactivity after menopause.

PMID- 21845339
TI  - Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene
      polymorphisms in the survival of head and neck cancer.
AB  - The association of education, tobacco smoking, alcohol consumption, and
      interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head
      and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of
      445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox
      regression was used to estimate hazard ratios (HR) and 95% confidence intervals
      (95%CI) of disease-specific survival according to anatomical sites of the head
      and neck. Mean age was 56 years and most patients were males (87.6%). Subjects
      with 5 or more years of schooling had better survival in larynx cancer. Smoking
      had no effect on HNSCC survival, but alcohol consumption had a statistically
      significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15
      1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with
      better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor
      survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI =
      0.61-2.85). IL-2 -384 G/T was associated with better survival in oral
      cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer
      (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for
      larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx
      cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42
      2.07), and C/C reduced mortality in larynx cancer. In general, our results are
      similar to previous reports on the value of education, smoking, alcohol
      consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC,
      but the risks due to these variables are small and estimates imprecise.

PMID- 21845340
TI  - Toxic effects of mercury, lead and gadolinium on vascular reactivity.
AB  - Heavy metals have been used in a wide variety of human activities that have
      significantly increased both professional and environmental exposure.
      Unfortunately, disasters have highlighted the toxic effects of metals on
      different organs and systems. Over the last 50 years, the adverse effects of
      chronic lead, mercury and gadolinium exposure have been underscored. Mercury and
      lead induce hypertension in humans and animals, affecting endothelial function in
      addition to their other effects. Increased cardiovascular risk after exposure to
      metals has been reported, but the underlying mechanisms, mainly for short periods
      of time and at low concentrations, have not been well explored. The presence of
      other metals such as gadolinium has raised concerns about contrast-induced
      nephropathy and, interestingly, despite this negative action, gadolinium has not
      been defined as a toxic agent. The main actions of these metals, demonstrated in
      animal and human studies, are an increase of free radical production and
      oxidative stress and stimulation of angiotensin I-converting enzyme activity,
      among others. Increased vascular reactivity, highlighted in the present review,
      resulting from these actions might be an important mechanism underlying increased
      cardiovascular risk. Finally, the results described in this review suggest that
      mercury, lead and gadolinium, even at low doses or concentrations, affect
      vascular reactivity. Acting via the endothelium, by continuous exposure followed
      by their absorption, they can increase the production of free radicals and of
      angiotensin II, representing a hazard for cardiovascular function. In addition,
      the actual reference values, considered to pose no risk, need to be reduced.

PMID- 21845341
TI  - Strength and power training did not modify cardiovascular responses to aerobic
      exercise in elderly subjects.
AB  - Resistance training increases muscle strength in older adults, decreasing the
      effort necessary for executing physical tasks, and reducing cardiovascular load
      during exercise. This hypothesis has been confirmed during strength-based
      activities, but not during aerobic-based activities. This study determined
      whether different resistance training regimens, strength training (ST, constant
      movement velocity) or power training (PT, concentric phase performed as fast as
      possible) can blunt the increase in cardiovascular load during an aerobic
      stimulus. Older adults (63.9 +/- 0.7 years) were randomly allocated to: control
      (N = 11), ST (N = 13, twice a week, 70-90% 1-RM) and PT (N = 15, twice a week, 30
      50% 1-RM) groups. Before and after 16 weeks, oxygen uptake (VO(2)), systolic
      blood pressure (SBP), heart rate (HR), and rate pressure product (RPP) were
      measured during a maximal treadmill test. Resting SBP and RPP were similarly
      reduced in all groups (combined data = -5.7 +/- 1.2 and -5.0 +/- 1.7%,
      respectively, P < 0.05). Maximal SBP, HR and RPP did not change. The increase in
      measured VO(2), HR and RPP for the increment in estimated VO(2) (absolute load)
      decreased similarly in all groups (combined data = -9.1 +/- 2.6, -14.1 +/- 3.9, 
      14.2 +/- 3.0%, respectively, P < 0.05), while the increments in the
      cardiovascular variables for the increase in measured VO(2) did not change. In
      elderly subjects, ST and PT did not blunt submaximal or maximal HR, SBP and RPP
      increases during the maximal exercise test, showing that they did not reduce
      cardiovascular stress during aerobic tasks.

PMID- 21845342
TI  - Electrocardiogram sensitivity in left ventricular hypertrophy according to gender
      and cardiac mass.
AB  - BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG)
      sensitivity when diagnosing Left Ventricular Hypertrophy (LVH), with gender and
      cardiac mass being two of the most important ones OBJECTIVE: To evaluate the
      influence of gender on the sensitivity of some of the criteria used to detect
      LVH, according to the progression of ventricular hypertrophy degree. METHODS:
      According to gender and the degree of LVH at the echocardiogram, the patients
      were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to
      detect LVH was assessed between men and women, according to the LVH degree.
      RESULTS: Of the 874 patients, 265 were males (30.3%) and 609, females (69.7%).
      The [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria
      showed high discriminatory power in the diagnosis of LVH between men and women in
      the three groups with LVH, with a superior performance in the male population and
      highlighting the importance of the [(S + R) X QRS] and Perugia scores.
      Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac
      mass. The examination is more sensitive in men, highlighting the importance of
      the [(S + R) X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of
      the ECG increases with the cardiac mass. The examination is more sensitive in
      men, highlighting the importance of the [(S + R) X QRS] and Perugia scores.

PMID- 21845343
TI  - Factors associated with increased radial augmentation index in hypertensive
      individuals.
AB  - BACKGROUND: Arterial stiffness is a variable predictor of morbidity and mortality
      and a possible marker of vascular injury. Its non-invasive assessment by radial
      tonometry and analysis of the augmentation index (r-AI) allows identifying
      patients exposed to higher cardiovascular risk. OBJECTIVE: To analyze the
      influence of r-AI on clinical-biochemical variables and its influence on the
      prevalence of target-organ damage in hypertensive patients. METHODS: 140
      consecutive hypertensive patients, followed-up in an outpatient clinic, were
      analyzed in a cross-sectional study. Blood pressure (BP) levels and r-AI were
      obtained by applanation tonometry of the radial artery (HEM-9000AI, Onrom). The
      patients were allocated into r-AI tertiles (r-AI < 85%; 85< r-AI < 97%; r-AI >
      97%). RESULTS: The sample was predominantly composed of women (56.4%), mean age
      of 61.7 +/- 11.7 years and body mass index 29.6 +/- 6.1 Kg/m2. The highest
      tertile showed higher proportion of women (p = 0.001), higher systolic BP (p =
      0.001) and pulse pressure (p = 0.014), and lower weight (p = 0.044), height (p <
      0.001) and heart rate (p < 0.001). Multivariate analysis demonstrated that weight
      (beta = -0.001, p = 0.017), heart rate (beta = -0.001, p = 0.007) and central
      pressure (beta = 0.015, p < 0.001) correlated independently with r-AI. In
      logistic regression analyses, the 3rd r-AI tertile was associated to lower levels
      of diabetes (DM) (OR = 0.41; 95% CI 0.17-0.97; p = 0.042). CONCLUSION: This study
      demonstrated that weight, heart rate and central BP were independently related to
      r-AI.

PMID- 21845344
TI  - Profile and scientific production of CNPq researchers in cardiology.
AB  - BACKGROUND: Systematic assessments of the scientific production can optimize
      resource allocation and increase research productivity in Brazil. OBJECTIVE: The
      aim of this study was to evaluate the profile and scientific production of
      researchers in the field of Cardiology who have fellowship in Medicine provided
      by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. METHODS:
      The curriculum Lattes of 33 researchers with active fellowships from 2006 to 2008
      were included in the analysis. The variables of interest were: gender,
      affiliation, tutoring of undergraduate, masters and PhD students, and scientific
      production and its impact. RESULTS: : There was predominance of males (72.7%) and
      of fellowship level 2 (56.4%). Three states of the Federation were responsible
      for 94% of the researchers: SP (28; 71.8%), RS (4; 10.3%), e RJ (3; 9.1%). Four
      institutions are responsible for about 82% of researchers: USP (13; 39.4%), UNESP
      (5; 15.2%), UFRGS (4; 12.1%) e UNIFESP (3; 9.1%). During all academic careers,
      the researchers published 2.958 journal articles, with a mean of 89 articles per
      researcher. Of total, 55% and 75% were indexed at Web of Science and Scopus
      databases, respectively. The researchers received a total of 19648 citations at
      the database Web of Science, with a median of 330 citations per researcher (IQ =
      198-706). The average number of citations per article was 13.5 citations (SD =
      11.6). CONCLUSION: Our study has shown that researchers in the field of
      cardiology have a relevant scientific production. The knowledge of the profile of
      researchers in the field of Cardiology will probably enable effective strategies
      to qualitatively improve the scientific output of Brazilian researchers.

PMID- 21845345
TI  - [Fetal surgery in Brazil].

PMID- 21845346
TI  - [Comparison of Doppler indexes to predict small infants for gestational age in
      pregnant women with hypertensive syndromes].
AB  - PURPOSE: to determine the best Doppler flow velocimetry index to predict small
      infants for gestational age (SGAI), in pregnant women with hypertensive
      syndromes. METHODS: a cross-sectional study was conducted enrolling 129 women
      with high blood pressure, submitted to doppler velocimetry up to 15 days before
      delivery. Women with multiple fetuses, fetal malformations, genital bleeding,
      placental abruption, premature rupture of fetal membranes, smoking, use of
      illicit drugs, and chronic diseases were excluded. A receiver operating
      characteristic (ROC) curve for each Doppler variable was constructed to diagnose
      SGAI and the sensitivity (Se), specificity (Sp), positive (PLR) and negative
      (NLR) likelihood ratio were calculated. RESULTS: the area under the ROC curve for
      the middle cerebral artery resistance index was 52% (p=0.79) with Se, Sp, PLR,
      and NLR of 25.0, 89.1, 2.3 and 0.84% for a resistance index lower than 0.70,
      respectively. While the area under the ROC curve for the resistance index of the
      umbilical artery was 74% (p=0.0001), with Se=50.0%, Sp=90.0%, PLR=5.0 and
      NLR=0.56, for a resistance index higher or equal to 0.70. The area under the ROC
      curve for the resistance index umbilical artery/middle cerebral artery ratio was
      75% (p=0.0001). When it was higher than 0.86, the Se, Sp, PLR and NLR were 70.8,
      80.0, 3.4 and 0.36%, respectively. For the resistance index of the middle
      cerebral artery/uterine artery ratio, the area under the ROC curve was 71%
      (p=0.0001). We found a Se=52.2%, Sp=85.9%, PLR=3.7 and NLR=0.56, when the ratio
      was lower than 1.05. When we compared the area under the ROC curve of the four
      doppler velocimetry indexes, we observed that only the resistance index umbilical
      artery/middle cerebral artery, resistance index middle cerebral artery/uterine
      artery and resistance index umbilical artery ratios seem to be useful for the
      prediction of SGA. CONCLUSION: in patients with high blood pressure during
      pregnancy, all doppler velocimetry parameters, except the middle cerebral artery
      resistance index, can be used to predict SGAI. The umbilical artery/middle
      cerebral artery ratio seems to be the most recommended one.

PMID- 21845347
TI  - [Validity of classical fetal weight charts in the Portuguese population].
AB  - PURPOSE: to assess the validity of several fetal weight charts, commonly used in
      Portugal, to classify its population. METHODS: observational retrospective study.
      Singleton birth data was analyzed, from a two- year period (May 2008 to April
      2010), from pregnancies with an ultrasound in the same institution, between the
      8th and 14th gestational week. Upon data validation, percentiles for each
      completed gestational week were created, smoothed by a quadratic function,
      analyzed and compared to the tables more commonly utilized, in the institution
      and country, by using Z-scores, percentile comparison, sample 10th percentile
      detection sensibility and birthweight means comparison. RESULTS: a total of 5,378
      newborns (NB) were born in the period; 2,195 (42%) NB were included, born from
      the 24th to 42nd gestational week, allowing statistical analysis from the 34th to
      the 41st week. There were differences in the mean birthweight for each
      gestational age, between references and with the sample, as well as between
      sexes. The 10th percentile from some references has shown differences ranging
      from -288g at 37 weeks (-11% in Lubchenco et al. data), with and +133g at 34
      weeks (+7,6% with Carrascosa et al. data) compared to the values found with the
      sample. Differences were also found concerning the sensitivity of the
      identification of a sample birthweight below the 10th percentile, which was
      between 14.1 and 100%, depending on the reference used. DISCUSSION: the
      limitation of these kinds of reference values must be remembered and minimized,
      with the adoption of regionally or nationally produced references, contemplating
      other variables, such as sex, with precisely known gestation duration and with
      validation of the utilized references in loco.

PMID- 21845348
TI  - [Screening of infection by human immunodeficiency virus at the time of delivery].
AB  - PURPOSE: to evaluate the frequency of HIV tests performed during prenatal care
      and rapid tests ordered for pregnant women admitted at the time of delivery.
      METHOD: this was a cross-sectional study with 711 pregnant women at delivery
      during the period from January to July 2010. Women admitted for clinical control
      and those that did not allow their clinical data to be included in the study were
      excluded. The chi2 test or the Fisher's Exact test was used for comparison of the
      proportion in univariate analysis. All the variables with p<0.25 were included in
      the logistic regression model, called initial model. The analyses were carried
      out using the SPSS software, with the level of significance set at 5%. RESULTS:
      the mean age of the patients was 25.77 +/-6.7 years and the maximum and minimum
      age was 44 and 12 years, respectively. The average gestational age at the time of
      attendance was 38.41 +/-6.7 weeks. Of these patients, 96.3% (n=685) had prenatal
      care and 11.1% (n=79) received prenatal care at our facility. The average number
      of prenatal care visits was 6.85 +/-2.88, but 28.1% had less than six visits. We
      identified 10 HIV-positive pregnant women (1.4%) and two patients were known to
      be HIV positive. The others (n=8) were screened at birth and therefore did not
      receive ARV prophylaxis during the prenatal period. Three patients were admitted
      during the expulsion period and also did not receive intrapartum antibiotic
      prophylaxis. However, all newborns were evaluated, with lactation being
      suppressed and artificial milk being used. CONCLUSIONS: despite the measures
      established by the Ministry of Health, there are still flaws in the approach to
      these patients. Only with the participation of managers and professionals
      involved in care it will be possible to correct the direct actions that enable
      the effective prevention of vertical transmission of HIV.

PMID- 21845349
TI  - [Nutritional status of lactanting adolescents in different postpartum weeks].
AB  - PURPOSE: to evaluate changes in the nutritional status of lactating adolescents
      in different postpartum weeks. METHOD: this is an analytical, observational,
      longitudinal study. Lactating adolescents were followed-up from the 5th to the
      15th postpartum week (PPW). The nutritional status was evaluated in the 5th, 10th
      and 15th PPW by the Body Mass Index (BMI/age). A colorimetric method was used to
      determine hemoglobin level and microcentrifugation to define hematocrit. ANOVA
      with repeated measures was used to compare means, followed by the Tukey post
      test. The level of significance was 5%. RESULTS: modification in nutritional
      status was observed from the pregestational period to the 15th PPW, with a
      reduction in the frequency of lactating adolescents with low weight (from 21% to
      9%) and a rise in the frequency of overweight (21% to 27%) and eutrophic (58% to
      64%) adolescents. Although mean hemoglobin (12.3 +/- 1.7 g/dL) and hematocrit
      (39.0 +/- 4.0%) levels were normal, a high frequency of anemia (30%) was observed
      throughout the study period. CONCLUSION: the present results show that the body
      weight of lactating adolescents rises during the lactation period and could lead
      to a higher frequency of obesity among adolescents. Anemia is still a nutritional
      problem, not only during pregnancy, but also during the postpartum period. It is
      necessary to prevent and treat probable subclinical nutritional deficiencies at
      this biological time.

PMID- 21845350
TI  - [Translation and validation into Portuguese of a questionnaire to evaluate the
      severity of urinary incontinence].
AB  - PURPOSE: to translate into Portuguese, culturally adapt and validate the
      Incontinence Severity Index (ISI) questionnaire. METHODS: two Brazilian
      translators carried out the translation of the ISI into Portuguese and a version
      was generated by consensus. This version was back-translated by two other native
      English speaking translators. The differences between versions were resolved and
      the version was pre-tested in a pilot study. One week later, the ISI was
      reapplied to complete the retest. The final version of the ISI was applied
      together with the one-hour pad test to women with stress urinary incontinence.
      For the validation of the ISI, the reliability (internal consistency and test
      retest) and the construct were evaluated. RESULTS: the reliability of the
      instrument was tested using the Cronbach alpha coefficient, with a general result
      of 0.93, demonstrating excellent reliability and consistency of the instrument.
      The intraclass correlation coefficient and the standard errors of measurement
      were 0.96 and 0.43, respectively. The Pearson correlation revealed a strong
      positive correlation (r=0.72, p<0.0001) between the results of the ISI
      questionnaire and the one-hour pad test. CONCLUSION: the culturally adapted
      version of the ISI translated into Brazilian Portuguese presented satisfactory
      reliability and survey validity and was considered to be valid for the evaluation
      of the severity of urinary incontinence.

PMID- 21845351
TI  - [Urinary symptoms and the pelvic floor muscle function after delivery].
AB  - PURPOSE: to evaluate the prevalence of urinary symptoms and association between
      pelvic floor muscle function and urinary symptoms in primiparous women 60 days
      after vaginal delivery with episiotomy and cesarean section after labor. METHODS:
      a cross-sectional analysis was conducted on women from an out patient clinic in
      Sao Paulo state, Brazil, 60 days after delivery. Pelvic floor muscle function was
      assessed by surface electromyography (basal tone, maximal voluntary contraction
      and mean sustained contraction) and by a manual muscle test (grades 0-5). In an
      interview, the urinary symptoms were identified and women with difficulty to
      understand, with motor/neurological impairment, pelvic surgery, diabetes,
      restriction for vaginal palpation and practicing exercises for pelvic floor
      muscles were excluded. The chi2 and Fisher Exact test were used to compare
      proportions and the Mann-Whitney test was used to analyze mean differences.
      RESULTS: 46 primiparous were assessed on average 63.7 days postpartum. The most
      prevalent symptoms were nocturia (19.6%), urgency (13%) and increased daytime
      urinary frequency (8.7%). Obese and overweight women had 4.6 times more of these
      symptoms (PR=4.6 [95%CI; 1.2-18.6; p value=0.0194]). Stress urinary incontinence
      was the most prevalent incontinence (6.5%). The mean values found for the basic
      tone, maximal voluntary contraction and sustained contraction were: 3 uV, 14.6 uV
      and 10.3 uV. Most of the women (56.5%) had grade 3 muscular strength. There was
      no association between urinary symptoms and pelvic floor muscle function.
      CONCLUSION: the prevalence of urinary symptoms was low 60 days postpartum and
      there was no association between pelvic floor muscle function and urinary
      symptoms.

PMID- 21845352
TI  - [Inflammatory bowel disease: Crohn's disease and pregnancy: case report].
AB  - The Crohn's disease, a form of inflammatory bowel disease, is frequent in women
      of childbearing age. Its management requires greater attention during pregnancy.
      We report a case of refractory Crohn's disease in a pregnant patient that evolued
      to ileocolectomy at puerperium. The literature regarding pregnant patients with
      Crohn's disease was reviewed, including counseling of patients and investigation
      of active disease, and the existing data was summarized on the safety of
      medications used to treat Crohn's disease in pregnancy and breastfeeding.

PMID- 21845353
TI  - Sleep problems and sickness absence among middle-aged employees.
AB  - OBJECTIVE: The aim of this study was to examine whether sleep problems predict
      subsequent sickness absence among middle-aged public sector employees. METHODS:
      The data included 5391 female and 1454 male employees of the City of Helsinki
      from questionnaire surveys at baseline in 2000-2002. These data were
      prospectively linked to the employer's sickness absence register data, with a
      mean follow-up time of 4.1 years. Using Poisson regression analysis, we examined
      associations between sleep problems (none, rare, occasional, and frequent), as
      indicated by the Jenkins Sleep Questionnaire, and self-certified short (1-3 days)
      and medically confirmed intermediate (4-14 days) and long (>=15 days) sickness
      absence spells. Sociodemographic factors, working conditions, work-family
      interface, health behaviors, and health status were obtained from the baseline
      surveys. RESULT: At baseline, 21% of women and 17% of men reported frequent sleep
      problems. Frequent sleep problems were associated with subsequent sickness
      absence spells irrespective of length of absence among both women and men after
      adjusting for age. After full adjustment for all covariates, the associations
      attenuated but remained for self-certified sickness absence [risk ratio (RR) for
      women 1.40, 95% confidence interval (95% CI) 1.25-1.56 and RR 1.59, 95% CI 1.24
      2.03 for men], and medically confirmed intermediate (RR 1.34, 95% CI 1.17-1.52
      and RR 1.35, 95% CI 1.02-1.77, for women and men, respectively) and long (RR
      1.58, 95% CI 1.29-1.94 and RR 1.44, 95% CI 0.93-2.21, for women and men,
      respectively) sickness absence spells. Occasional sleep problems were also
      associated with sickness absence, but the associations were somewhat weaker.
      CONCLUSION: In occupational healthcare, sleep problems should be addressed to
      prevent their occurrence and subsequent ill-health and sickness absence.

PMID- 21845355
TI  - [Meeting of the Working Group on Gynecological and Breast Pathology].

PMID- 21845357
TI  - [Report of the Working Group on Orthopedic Pathology].

PMID- 21845356
TI  - [High-grade prostatic intraepithelial neoplasia: the only accepted prostate
      cancer precursor lesion].
AB  - For many tumors the early detection of precursor lesions of invasive cancer has
      an impact on the clinical course. The high-grade prostatic intraepithelial
      neoplasia (HG-PIN) is the only accepted facultative precursor lesion for acinar
      prostate cancer. While HG-PIN shows many similarities to prostate cancer it is
      most probably not a precursor of every prostate cancer variant. However, the
      detection of HG-PIN in needle biopsies is a significant risk factor for the
      subsequent diagnosis of invasive prostate cancer. Low-grade PIN (LG-PIN),
      proliferative inflammatory atrophy (PIA), and atypical adenomatous hyperplasia
      are no longer considered to be true precursor lesions.

PMID- 21845354
TI  - Drug therapy of post-stroke aphasia: a review of current evidence.
AB  - This review considers the role of drug therapy in the treatment of post-stroke
      aphasia, the evidence for efficacy of different agents, and the theory-based
      explanations of drug-related benefits for aphasia rehabilitation. Pharmacological
      interventions modulating stroke-induced disruption of diverse neurotransmitters
      may improve language and communication deficits in aphasic patients through
      facilitation of brain plasticity and long-term potentiation. However, benefits
      are not evident for all compounds and refinement in clinical trial designs is
      required. Some pharmacological trials have failed because drug treatment was not
      combined with speech-language therapy, while other trials combining drugs with
      intensive model-driven therapies also failed probably because of short-trial
      duration, inadequate sample selection, or lack of drug action. Preliminary data
      reveals that combining neuroscience-based intensive aphasia techniques
      (constraint-induced aphasia therapy) and drugs acting on cholinergic and
      glutamatergic neurotransmitter systems are associated with better outcomes than
      other strategies and long-term maintenance of benefits. Although further studies
      are needed, current state of the evidence suggests that drug therapy may play a
      key role in the treatment of post-stroke aphasia.

PMID- 21845358
TI  - [Non-serrated precursor lesions of colorectal tumours].
AB  - Non-serrated precursor lesions of colorectal tumours include conventional
      adenomas (tubular, tubulovillous and villous), inflammatory bowel disease
      associated dysplasia (intraepithelial neoplasia), and hamartoma-associated
      dysplasia. This short review summarizes the current literature on the adenoma
      carcinoma sequence, focusing on colonic stem cells and functional crypt
      organization, patterns of stem cell division, niche succession and clonal
      conversion in the formation of a monocryptal adenoma. The process of clonal
      interaction between neighboring crypts as well as the development of large
      monoclonal adenomas from small polyclonal precursor lesions is discussed in
      detail. Finally, the molecular pathogenesis as well as the clinical significance
      of inflammatory bowel disease- and hamartoma-associated carcinogenesis is
      addressed.

PMID- 21845359
TI  - [Evaluation of a renal biopsy: what information is important for nephrologists?].
AB  - A kidney biopsy is an important and frequently used diagnostic tool in routine
      nephrology. In order to obtain relevant clinical information from a renal biopsy
      close cooperation between clinicians and pathologists is mandatory. The better
      the information obtained from nephrologists and the better the understanding by
      nephrologists and the quality of the kidney biopsy, the more rewarding is the
      information from pathologists. The following paper will discuss some practical
      aspects regarding the interaction between nephrology and pathology which may not
      be known or poorly handled and may thus cause misunderstanding. In order to
      facilitate interaction between clinicians and pathologists some guidelines
      concerning the procedure and work-up of routine kidney biopsies have been
      established and will be discussed in detail.

PMID- 21845360
TI  - [Molecular diagnosis of HPV infections].
AB  - Carcinogenic human papillomaviruses (HPV) cause the majority of cervical cancers
      and other anogenital cancers. Large randomized trials have shown that HPV testing
      can be efficiently used for primary cervical cancer screening. Other applications
      include the triage of abnormal cytology results and the follow-up of women after
      treatment. Many assays have been developed to measure DNA, RNA and proteins of
      HPV and the various tests can have very different applications. It is important
      to rigorously validate HPV assays before they are implemented in screening or
      clinical care.

PMID- 21845361
TI  - [Mitosis in early invasive malignant melanoma. How reliable is histogenetic
      classification at stage pT1?].
AB  - Since early February 2010 we have been implementing the latest version of the
      2009 AJCC Melanoma Staging and Classification in our institution. Since,
      according to the guidelines for stage pT1 melanomas, the number of mitoses/mm(2)
      is of particular significance, we have been able to observe a notable shift from
      pT1a to pT1b. Highlighting the mitotic count as one of the key features of the
      diagnosis of malignant melanoma, we observed that the major part of stage
      switched melanomas belonged to a minimally invasive subset of melanomas
      previously categorized as pT1a UICC (7(th) edition). A level of reasonable doubt
      remains regarding the distinct histogenetic classification of mitosis as early
      stage melanoma with regard to their epithelial or melanocytic origin.

PMID- 21845362
TI  - 1H, 13C, and 15N resonance assignments and secondary structure prediction of the
      full-length transition state regulator AbrB from Bacillus anthracis.
AB  - The AbrB protein is a transcription factor that regulates the expression of
      numerous essential genes during the cells transition phase state. AbrB from
      Bacillus anthracis is, nototriously, the principal protein responsible for
      anthrax toxin gene expression and is highly homologous to the much-studied AbrB
      protein from Bacillus subtilis having 85% sequence identity and the ability to
      regulate the same target promoters. Here we report backbone and sidechain
      resonance assignments and secondary structure prediction for the full-length AbrB
      protein from B. anthracis.

PMID- 21845363
TI  - Backbone and sidechain 1H, 13C and 15N chemical shift assignments of the
      hydrophobin DewA from Aspergillus nidulans.
AB  - Hydrophobins are proteins secreted by filamentous fungi that are able to self
      assemble into monolayers at hydrophobic:hydrophilic interfaces. The layers are
      amphipathic and can reverse the wettability of surfaces. Hydrophobins have
      several roles in fungal development, including the formation of coatings on
      fungal structures to render them hydrophobic. Here we report the backbone and
      sidechain assignments for the class I hydrophobin DewA from the fungus
      Aspergillus nidulans.

PMID- 21845364
TI  - Vitamin D metabolism and signaling in the immune system.
AB  - Vitamin D has emerged as a pleiotropic regulator of human physiology, and recent
      work has revealed that it has several roles in control of human immune system
      function. Vitamin D was originally characterized for its role in calcium
      homeostasis, and the active form, 1,25-dihydroxyvitamin D (1,25D), can be
      produced in the kidney by 1alpha-hydroxylation of circulating 25-hydroxyvitamin D
      catalyzed by the enzyme CYP27B1. Renal CYP27B1 expression is regulated by calcium
      regulatory inputs, and 1,25D produced in the kidney was thought to function
      largely as an endocrine hormone. However, it is now clear that CYP27B1 is
      expressed in numerous tissues, and that 1,25D acts at several sites in the body
      in an intracrine or paracrine manner. In particular, both CYP27B1 and the vitamin
      D receptor (VDR) are expressed in several cell types in the immune system, where
      CYP27B1 production is controlled by a number of immune-specific inputs. Recent
      research has opened several windows on the molecular mechanisms by which 1,25D
      signaling regulates both innate and adaptive immune responses in humans.
      Moreover, intervention trials are beginning to provide evidence that vitamin D
      supplementation can bolster clinical responses to infection. This review will
      discuss recent developments in our understanding of how immune signaling controls
      local vitamin D metabolism and how, in turn, the 1,25D-bound VDR modulates immune
      system function. A particular emphasis will be placed on the interplay between
      vitamin D signaling and signaling through different classes of pattern
      recognition receptors in the production of antimicrobial peptides during innate
      immune responses to microbial infection.

PMID- 21845367
TI  - Bioaccumulation and glutathione-mediated detoxification of copper and cadmium in
      Sphagnum squarrosum Crome Samml.
AB  - Physiological and biochemical responses, metal bioaccumulation and tolerance
      potential of Sphagnum squarrosum Crome Samml. to Cu and Cd were studied to
      determine its bioindication and bioremediation potential. Results suggest that
      glutathione treatment increases the metal accumulation potential and plays a
      definite role in heavy metal scavenging. High abundance of Sphagnum in metal-rich
      sites strongly suggests its high metal tolerance capabilities. This experiment
      demonstrates that S. squarrosum is able to accumulate and tolerate a high amount
      of metals and feasibility of its application as bioindicator and remediator test
      species of metal-contaminated environment.

PMID- 21845365
TI  - Vitamin D and the skin: Physiology and pathophysiology.
AB  - The keratinocytes of the skin are unique in being not only the primary source of
      vitamin D for the body, but in possessing both the enzymatic machinery to
      metabolize the vitamin D produced to active metabolites (in particular
      1,25(OH)(2)D) and the vitamin D receptor (VDR) that enables the keratinocytes to
      respond to the 1,25(OH)(2)D thus generated. Numerous functions of the skin are
      regulated by vitamin D and/or its receptor. These include inhibition of
      proliferation, stimulation of differentiation including formation of the
      permeability barrier, promotion of innate immunity, regulation of the hair
      follicle cycle, and suppression of tumor formation. Regulation of these actions
      is exerted by a number of different coregulator complexes including the
      coactivators vitamin D receptor interacting protein (DRIP) complex also known as
      Mediator and the steroid receptor coactivator (SRC) family (of which SRC 2 and 3
      are found in keratincytes), the inhibitor hairless (Hr), and beta-catenin whose
      impact on VDR function is complex. Different coregulators appear to be involved
      in different VDR regulated functions. This review will examine the various
      functions of vitamin D and its receptor in the skin, and explore the mechanisms
      by which these functions are regulated.

PMID- 21845368
TI  - Oxidized low density lipoproteins--do we know enough about them?
AB  - Since the discovery of oxidized low density lipoprotein (Ox-LDL), over 5,000
      articles have appeared on the topic with over 400 articles appearing every year
      during the past decade. LDL contains esterified polyunsaturated fatty acid
      containing lipids, such as, phosphatidylcholine (PtdCho) and cholesterol esters
      (CE). Peroxidation of polyunsaturated fatty acid (PUFA) containing lipids has
      been known for a long time. Numerous studies have documented that peroxidized
      lipids as well as products derived from their decomposition, particularly
      aldehydes, have deleterious biological properties. This concept has been
      exemplified in the study of atherosclerosis. A plethora of in vitro and animal
      studies, as well as human epidemiological and correlatory studies, have supported
      the notion that oxidative processes and the formation of Ox-LDL might contribute
      to atherosclerosis. Yet the negative outcomes of human clinical trials with alpha
      tocopherol and other antioxidants have convinced even staunch supporters of the
      hypothesis to take a step backwards and reconsider reasons of their failure and
      suggest alternative approaches. Ox-LDL is a complex mixture of numerous chemical
      entities, many of them are yet uncharacterized. Why and how it is formed or its
      nature in vivo is poorly understood. It is recognized by numerous cell surface
      receptors, which are ubiquitously expressed in many different cell types. These
      receptors might perform a variety of functions. In addition, components of Ox-LDL
      might also have favorable effects that are difficult to dissociate from its
      pathological effects. In this review, the nature of Ox-LDL and potential problems
      in inhibiting its formation are discussed.

PMID- 21845366
TI  - Extragonadal actions of chorionic gonadotropin.
AB  - The primary embryonic signal in primates is chorionic gonadotropin (CG,
      designated hCG in humans), that is classically associated with corpus luteum
      rescue and progesterone production. However, research over the past decade has
      revealed the presence of the hCG receptor in a variety of extragonadal tissues.
      Additionally, discoveries of the multiple variants of hCG, namely, native hCG,
      hyperglycosylated hCG (hyp-hCG) and the beta- subunit of the hyperglycosylated
      hCG (hCG-free beta) has established a role for extragonadal actions of hCG. For
      the initiation and maintenance of pregnancy, hCG mediates multiple placental,
      uterine and fetal functions. Some of these include development of
      syncytiotrophoblast cells, mitotic growth and differentiation of the endometrium,
      localized suppression of the maternal immune system, modulation of uterine
      morphology and gene expression and coordination of intricate signal transduction
      between the endometrium. Recurrent pregnancy loss, pre-eclampsia and
      endometriosis are associated with altered responses of hCG, all of which have a
      detrimental effect on pregnancy. A role for hyp-hCG in mediating the development
      of both trophoblastic and non-trophoblastic tumors has also been suggested. Other
      significant non-gonadal applications of hCG include predicting preeclampsia,
      determining the risk of Down's syndrome and gestational trophoblastic disease,
      along with relaxing myometrial contractility and preventing recurrent
      miscarriages. Presence of hCG free-beta in serum of cancer patients enables its
      usage as a diagnostic tumor marker. Thus, the extragonadal functions of hCG
      encompasses a wide spectrum of applications and is an open area for continued
      investigation.

PMID- 21845369
TI  - Simultaneously occurring tumours within the same cerebello-pontine angle:
      refining literature definitions and proposal for classification.
AB  - We report on an unusual case of a patient, not affected by neurofibromatosis,
      harbouring two radiologically spatially contiguous tumours within the same
      cerebello-pontine angle. Pathological findings were consistent with the diagnosis
      of two spatially distinct primary tumours, namely a meningioma and a schwannoma.
      We proposed a classification of tumours occurring at the same location consistent
      with the different spatial arrangement and histological nature of these
      conditions. The correct classification of these nosological entities will allow
      further more accurate evaluations of these cases in order to clarify the
      pathogenesis, prognosis and best treatment of each one.

PMID- 21845370
TI  - Subtemporal transtentorial resection of cavernous malformations involving the
      pyramidal tract in the upper pons and mesencephalon.
AB  - BACKGROUND: Lateral approaches to the brain stem for the resection of the
      cavernous malformations are preferred in order to avoid the structures within the
      floor of the fourth ventricle. The entry behind the pyramidal tract (PT) is
      usually carried out through the posterolateral surface of the brain stem. The
      more straightforward lateral approach below the temporal lobe is used rarely
      because of potential risks. METHODS: The outcome after resection of the
      cavernomas involving the PT in the mesencephalon and the upper pons via the
      subtemporal transtentorial approach in nine patients was analysed. Mapping of the
      PT by direct electrical stimulation was used in the last four patients. RESULTS:
      The subtemporal transtentorial approach enabled adequate exposure of the lateral
      and anterolateral surface of the midbrain and the upper pons. No adverse events
      from the elevation of the temporal lobe were encountered. Direct electrical
      stimulation using a bipolar electrode with the parameters of 100 Hz, 1 ms, and 3
      9 mA evoked motor responses in three of four patients. It allowed placing the
      incision in the lateral surface of the midbrain behind the PT or between the
      fibres of the upper and the lower extremity. No worsening of the PT functions was
      observed in the series. CONCLUSIONS: The subtemporal transtentorial approach
      enables adequate exposure of the lateral and the anterolateral surface of the
      mesencephalon and upper pons, allowing neurophysiological mapping of the PT and
      thus avoiding its damage during removal of the cavernoma.

PMID- 21845371
TI  - A fluorescence and fluorescence probe study of benzonaphthyridines.
AB  - A series of benzo[b][1,8]naphthyridines has been synthesized by Friedlander
      condensation of 2-aminoquinoline-3-carbaldehyde 1 (o-aminoaldehyde) with
      alicyclic ketones in basic medium. Benzonaphthyridines branched with various side
      chains and substituents are prepared with the aim of being investigated as a good
      fluorescent material. Electronic absorption and fluorescence properties of some
      representative benzonaphthyridines in organic solvents, water-dioxane, and SDS,
      CTAB and Triton-X-100 micelles have been examined. The linear correlation between
      solvent polarity and fluorescence properties is observed. This study may provide
      new directions for the development of fluorescence probes as reporters of
      microenvironments of organized assemblies.

PMID- 21845372
TI  - Spectroscopic and molecular modeling studies of the interaction between 4'-O
      (alpha-L-oleandrosyl)daunorubicin and human serum albumin and its analytical
      application.
AB  - 4'-O-(alpha-L-oleandrosyl)daunorubicin (ODNR) is a disaccharide analogue of
      daunorubicin with potent antitumor activity against leukemia cell line K562 cells
      and colon cancer cell line SW620 cells. In this paper, the binding interaction of
      ODNR with human serum albumin (HSA) was investigated under simulative
      physiological conditions by fluorescence spectroscopy in combination with UV
      absorption spectroscopy and molecular modeling method. A strong fluorescence
      quenching reaction of ODNR to HSA was observed and the quenching mechanism was
      suggested as static quenching according to the Stern-Volmer equation. The binding
      constants (K) at different temperatures as well as thermodynamic parameters,
      enthalpy change (DeltaH) and entropy change (DeltaS), were calculated according
      to relevant fluorescent data and Van't Hoff equation. The hydrophobic interaction
      was a predominant intermolecular force in order to stabilize the complex, which
      was in agreement with the results of molecular modeling study. In addition, the
      effects of other ions on the binding constants were also studied. Moreover, the
      synchronous fluorescence technique was successfully employed to determine the
      total proteins in serum, urine and saliva samples at room temperature under the
      optimum conditions with a wide linear range and satisfactory results.

PMID- 21845373
TI  - Determination of Judd-Ofelt intensity parameters of pure samarium(III) complexes.
AB  - This work reports an alternative aproach to obtain the Judd-Ofelt intensity
      parameters of Sm(III) complexes with the general formula: [Sm(tta)(3)(L)(n)],
      with L = H(2)O, triphenylphosphine oxide (tppo), 2,2'-bipyridine (bipy) and 1,10
      phenantroline (phen); n = 2 for H(2)O and tppo and n = 1 for phen and bipy, using
      the absorption spectra of rare earth complexes where the powders are dispersed in
      KBr pellets. This approach can be applied to other complexes of rare earth ions
      that have spin allowed transitions and it is validated by comparing the emission
      spectra of the complexes with those dispersed in KBr pellets.

PMID- 21845374
TI  - Pancreatic involvement by plasma cell neoplasms.
AB  - INTRODUCTION: Pancreatic involvement by plasma cell neoplasms is an extremely
      rare event, with only 50 cases described in the literature. They can present as a
      primary solitary extramedullary plasmacytoma or plasmacytoma secondary to a
      plasma cell myeloma. Clinical manifestations are due to the presence of a
      pancreatic mass usually in the pancreas head, which causes extra-biliary
      obstruction and abdominal pain. METHODS: Abdominal imaging including CT scan or
      endoscopic ultrasound with fine-needle aspiration tissue sampling is essential
      for the initial diagnostic procedure. However, immunohistochemical analysis of
      the biopsy specimen or flow cytometry of the aspirated material is crucial to
      prove the monoclonality and the final diagnosis of a plasma cell neoplasm.
      DISCUSSION: Management of these situations include radiotherapy, chemotherapy,
      surgery or combined therapy. Novel medications including the immunomodulatory
      drugs or the proteasome inhibitors followed by consolidation with intensive
      chemotherapy and haematopoietic stem cell transplantation are nowadays used as
      upfront treatment in the cases associated to a plasma cell myeloma. CONCLUSION:
      Despite the rarity, plasma cell neoplasms should be considered in the
      differential diagnosis of obstructive jaundice and pancreatic neoplasms since
      they are potentially treatable situations.

PMID- 21845376
TI  - Dunking pancreaticojejunostomy versus duct-to-mucosa anastomosis.
AB  - Following the resectional aspect of pancreaticoduodenectomy, three anastomoses
      are used to reestablish gastrointestinal continuity. The pancreatic-enteric
      anastomosis is by far the most problematic, and has been considered by many the
      Achilles heel of the pancreaticoduodenal resection. Multiple clinical trials have
      been published focusing on improving outcomes of the pancreatic-enteric
      anastomosis, including elements such as the use of prophylactic octreotide, the
      use of sealants, stenting of the pancreatic duct, and surgical technique. There
      are two widely used methods to accomplish an end-to-side pancreaticojejunostomy
      (PJ) after pancreaticoduodenectomy: either invagination PJ or duct-to-mucosa PJ.
      Two prospective randomized trials have evaluated these techniques, the first a
      trial by Bassi and co-authors, and the second a trial by Berger et al. In this
      article we will focus on our current technique for both invagination
      pancreaticojejunostomy and duct-to-mucosa pancreaticojejunostomy, recognizing
      that careful surgical technique, surgeon experience, and surgical volume are
      factors that are important in yielding the best outcomes. 

PMID- 21845375
TI  - Advances in small bowel imaging.
AB  - The small intestine has been difficult to examine by traditional endoscopic and
      radiologic techniques. Within the past 10 years, advances have led to an
      explosion of technologies that facilitate examination of the entire small
      intestine. Wireless video capsule endoscopy, deep enteroscopy using balloon
      assisted or spiral techniques, computer tomography (CT) and magnetic resonance
      (MR) enterography have facilitated the diagnosis, monitoring, and management of
      patients with small intestinal diseases. These technologies are complementary,
      each with its advantages and limitations. Capsule endoscopy provides a detailed
      view of the mucosal surface and has excellent patient acceptance, but does not
      allow therapeutics. Deep enteroscopy allows careful inspection of the mucosa and
      therapeutics, but is time consuming and invasive. Enterography (CT or MR) allows
      examination of the small bowel wall and surrounding structures. The initial best
      test for detecting small intestinal disease depends on clinical presentation and
      an astute differential diagnosis.

PMID- 21845377
TI  - Association of low serum adiponectin levels with erosive esophagitis in men: an
      analysis of 2405 subjects undergoing physical check-ups.
AB  - BACKGROUND: Obesity is a risk factor for gastro-esophageal reflux disease (GERD).
      It is generally considered that intra-abdominal pressure in obese subjects is
      involved in the pathogenesis of GERD through acid exposure to the esophagus.
      Recently, visceral fat has been recognized as an endocrine organ that secretes
      various adipocytokines including adiponectin. The aim of this study was to
      elucidate the relation between adiponectin and erosive esophagitis. METHODS: This
      was a cross-sectional retrospective observational study: 2405 consecutive
      subjects who underwent screening esophago-gastro-duodenoscopy with serum
      adiponectin measurement as part of their physical check-up programs were
      analyzed. Clinical factors were compared between subjects with and without
      erosive esophagitis. The association between adiponectin and erosive esophagitis
      was assessed using a bootstrapping re-sampling method after adjustment for
      factors that tended to be different in univariate analysis. RESULTS: Serum
      adiponectin levels were significantly lower in those with erosive esophagitis
      (8.17 MUg/ml) than in those without (10.1). The erosive esophagitis group had a
      greater body mass index (BMI) and waist circumference (WC) and a higher
      prevalence of hiatal hernia. Using the bootstrap method, with a lower adiponectin
      cut-off value of 3-7 MUg/ml, the lower limit of the 95% confidence interval of
      the adjusted odds ratio consistently exceeded 1 after adjustment for BMI and
      hiatal hernia in men. When adjusting for WC instead of BMI, the effect of
      adiponectin was reduced but remained significant at a lower cut-off value (3-3.5
      MUg/ml). CONCLUSIONS: Low serum adiponectin levels may be associated with an
      increased risk for erosive esophagitis in men.

PMID- 21845378
TI  - Percutaneous radiofrequency ablation therapy for hepatocellular carcinoma: a
      proposed new grading system for the ablative margin and prediction of local tumor
      progression and its validation.
AB  - BACKGROUND: In the present study we classified the radicality of percutaneous
      radiofrequency thermal ablation (RFA) therapy according to the extent of the
      ablated margin. We measured the local recurrence rate for each radicality grade
      to evaluate the significance of the grading system in assessing the therapeutic
      effectiveness of RFA and predicting local tumor progression. METHODS: This
      retrospective study involved 269 patients with solitary hypervascular
      hepatocellular carcinoma who had undergone RFA. The mean +/- SD observation
      period after RFA, number of treatment sessions, and tumor diameter were 25.7 +/-
      19.9 months, 1.2 +/- 0.5, and 2.1 +/- 0.7 cm, respectively. Patients were
      evaluated using dynamic computed tomography. We classified the radicality of RFA
      treatment into four grades (R grades: A, B, C, and D) according to the extent of
      the ablated tumor margin, calculated the post-RFA cumulative local recurrence
      rate for each R grade, and analyzed the factors (patient characteristics,
      biochemical data, contiguous vessels, and tumor marker) contributing to local
      recurrence. RESULTS: The cumulative local recurrence rates at 3 years were 6.7,
      17.6, 55.8, and 82.2% for Grades A, B, C, and D, respectively. Using univariate
      analysis, R grade, tumor size (> 2 cm), and des-gamma-carboxy prothrombin (DCP)
      (> 200 mA U/mL) were shown to be significant factors contributing to local
      recurrence. However, using multivariate analysis, only the R grade was found to
      be a significant independent factor. CONCLUSIONS: The proposed R grading method
      is a valid and useful method for assessing treatment efficacy, and for predicting
      local tumor progression after RFA.

PMID- 21845379
TI  - A developmental neuroscience of borderline pathology: emotion dysregulation and
      social baseline theory.
AB  - Theoretical and empirical research has linked poor emotion regulation abilities
      with dysfunctional frontolimbic circuitry. Consistent with this, research on
      borderline personality disorder (BPD) finds that frontolimbic dysfunction is a
      predominant neural substrate underlying the disorder. Emotion regulation is
      profoundly compromised in BPD. However, BPD is also associated with broad
      impairment across multiple domains, including impulse control, interpersonal
      relationships, and cognitive functioning. To date, BPD research has focused
      largely on single areas of dysfunction, failing to account for overlap at either
      the biological or behavioral levels of analysis. We examine the literature on
      frontolimbic dysfunction in BPD within the context of Coan's social baseline
      theory. Social baseline theory proposes that healthy human functioning is
      dependent upon adequate social support and that, at baseline, biological systems
      are adapted to operate interdependently rather than independently. The social
      baseline perspective is particularly useful for understanding borderline
      personality development because the impulsive and emotionally dysregulated
      behaviors common among those with BPD occur almost invariably within an
      interpersonal context. We discuss clinical and research implications of this
      work.

PMID- 21845381
TI  - Does metformin work for everyone? A genome-wide association study for metformin
      response.

PMID- 21845380
TI  - Elevated appraisals of the negative impact of naturally occurring life events: a
      risk factor for depressive and anxiety disorders.
AB  - The tendency to appraise naturally occurring life events (LEs) as having high
      negative impact may be a predisposing factor for the development of depression
      and anxiety disorders. In the current study, appraisals of the negative impact of
      recent LEs were examined in relationship to depressive and anxiety disorders in a
      sample of 653 adolescents who were administered diagnostic and life stress
      interviews at ages 15 and 20. Participants' appraisals of the negative impact of
      LEs reported at age 15 were statistically adjusted using investigator-based
      ratings to control for objective differences across LEs. Higher appraisals of the
      negative impact of LEs were associated with both past and current depressive and
      anxiety disorders at age 15 and predicted subsequent first onsets of depressive
      and anxiety disorders occurring between ages 15 and 20. In addition, appraisals
      of the negative impact of LEs were particularly elevated among those experiencing
      both a depressive and anxiety disorder over the course of the study. The findings
      suggest that systematically elevated appraisals of the negative impact of LEs are
      a predisposing factor for depression and anxiety disorders and may represent a
      specific risk factor for co-morbid depression and anxiety in mid-adolescence and
      early adulthood.

PMID- 21845382
TI  - Tc-99m-BrIDA hepatobiliary (HIDA) scan has a low sensitivity for detecting
      biliary complications after orthotopic liver transplantation in patients with
      hyperbilirubinemia.
AB  - BACKGROUND: Tc-99m-BrIDA hepatobiliary scans are noninvasive tests for detecting
      biliary leaks and obstructions. However, there is low sensitivity and specificity
      in patients with hyperbilirubinemia. Biliary complications (BC) are the Achilles
      heel of orthotopic liver transplantation (OLT). We questioned whether
      hyperbilirubinemia in liver transplant recipients rendered HIDA scanning less
      dependable. METHODS: HIDA findings were compared to endoscopic retrograde
      cholangiopancreatography, laparotomy, and clinical course. Results were
      categorized as follows: true positive (TP), true negative (TN), false positive
      (FP), false negative (FN), or nondiagnostic/inconclusive. We searched for
      variables associated with erroneous or nondiagnostic tests which we defined as
      all examinations determined to be FP, FN and/or nondiagnostic/inconclusive.
      RESULTS: Thirty-four patients underwent a HIDA scan. The sensitivity and
      specificity were 70 and 100%. The sensitivity of HIDA improved to 100% in
      patients with a total bilirubin (TB) <5 mg/dl. Inconclusive and FN patients had a
      total bilirubin >5 mg/dl. One FN had a TB <5 mg/dl, but was determined
      inconclusive due to the roux-en-Y. CONCLUSION: HIDA scans performed when the
      total bilirubin was <5 mg/dl had a high sensitivity and specificity for detecting
      biliary complications after OLT. However, when the total bilirubin exceeded 5
      mg/dl, the specificity was still 100% but the numbers of
      nondiagnostic/inconclusive and FN exams were increased.

PMID- 21845383
TI  - Microarray analysis highlights immune response of pacific oysters as a
      determinant of resistance to summer mortality.
AB  - Summer mortality of Crassostrea gigas is the result of a complex interaction
      between oysters, their environment, and pathogens. A high heritability was
      estimated for resistance to summer mortality, which provided an opportunity to
      develop lines of oysters that were resistant (R) or susceptible (S) to summer
      mortality. Previous genome-wide expression profiling study of R and S oyster
      gonads highlighted reproduction and antioxidant defense as constitutive pathways
      that operate differentially between these two lines. Here, we show that signaling
      in innate immunity also operates differentially between these lines, and we
      hypothesize that this is at the main determinant of their difference in survival
      in the field. A reanalysis of our published microarray data using separate ANOVAs
      at each sampling date revealed a specific "immune" profile at the date preceding
      the mortality. In addition, we conducted additional microarray profiling of two
      other tissues, gills, and muscle, and both showed an overrepresentation of immune
      genes (46%) among those that are differentially expressed between the two lines.
      Eleven genes were pinpointed to be simultaneously differentially expressed
      between R and S lines in the three tissues. Among them, ten are related to
      "Immune Response." For these genes, the kinetics of R mRNA levels between
      sampling dates appeared different just before the morality peak and suggests that
      under field conditions, R oysters had the capacity to modulate signaling in
      innate immunity whereas S oysters did not. This study enhances our understanding
      of the complex summer mortality syndrome and provides candidates of interest for
      further functional and genetics studies.

PMID- 21845384
TI  - Extracellular metalloproteases from bacteria.
AB  - Bacterial extracellular metalloproteases (BEMPs) are a large group of metal
      containing proteases secreted by heterotrophic bacteria. In this review, the
      diversity, structural characteristics, mechanisms of maturation, physiological
      roles, and applications of BEMPs are described. BEMPs are distributed among nine
      families of metalloproteases because of differences in primary sequences and
      structural characteristics. Until now, all of the BEMPs identified have been
      endoproteases harboring one catalytic Zn(2+) in the active centers. BEMPs are
      usually synthesized as inactive zymogens with a propeptide that is covalently
      linked to and inhibits the catalytic domain. The removal of the propeptides of
      BEMPs is dependent on other proteases or an autocleavage process. The main
      physiological function of BEMPs is to degrade environmental proteins and peptides
      for bacterial heterotrophic nutrition. As extracellular proteases, BEMPs vary
      greatly in enzymology properties to adapt to their respective environments. BEMPs
      have been widely used in the food and pharmaceutical industries. In order to
      broaden the application of BEMPs, it is essential to explore novel BEMPs and
      apply gene/protein engineering to improve the production and properties of
      promising BEMPs.

PMID- 21845385
TI  - Extracellular production of Streptomyces exfoliatus poly(3-hydroxybutyrate)
      depolymerase in Rhodococcus sp. T104: determination of optimal biocatalyst
      conditions.
AB  - The phaZ ( Sex ) gene encoding poly(3-hydroxybutyrate) depolymerase from
      Streptomyces exfoliatus has been successfully cloned and expressed in Rhodococcus
      sp. T104 for the first time. Likewise, the recombinant enzyme was efficiently
      produced as an extracellular active form and purified to homogeneity by two
      hydrophobic chromatographic steps. MALDI-TOF analysis showed that the native
      enzyme is a monomer. Circular dichroism studies have revealed a secondary
      structure showing 25.6% alpha-helix, 21.4% beta-sheet, 17.1% beta-turns, and
      35.2% random coil, with a midpoint transition temperature (T (m)) of 55.8 
      degrees C. Magnesium and calcium ions enhanced the enzyme activity, whereas
      manganese inhibited it. EDTA moderately decreased the activity, and the enzyme
      was completely deactivated at 3 M NaCl. Chemical modification studies indicated
      the presence of the catalytic triad serine-histidine-carboxylic acid in the
      active site. High-performance liquid chromatography (HPLC)-mass spectrometry (MS)
      analysis of PHB products of enzymatic hydrolysis showed monomers and dimers of 3
      hydroxybutyric acid, demonstrating that PHB depolymerase is an exo-hydrolase.
      Addition of methyl-beta-cyclodextrin simultaneously increased the activity as
      well as preserved the enzyme during lyophilization. Finally, thermoinactivation
      studies showed that the enzyme is highly stable at 40  degrees C. All these
      features support the potential industrial application of this recombinant enzyme
      in the production of (R)-3-hydroxyalkanoic acid derivatives as well as in the
      degradation of bioplastics.

PMID- 21845386
TI  - Investigation of the potential of biocalorimetry as a process analytical
      technology (PAT) tool for monitoring and control of Crabtree-negative yeast
      cultures.
AB  - Biological reaction calorimetry, also known as biocalorimetry, has led to
      extensive applications in monitoring and control of different bioprocesses. A
      simple real-time estimator for biomass and growth rate was formulated, based on
      in-line measured metabolic heat flow values. The performance of the estimator was
      tested in a unique bench-scale calorimeter (BioRC1), improved to a sensitivity
      range of 8 mW l(-1) in order to facilitate the monitoring of even weakly
      exothermic biochemical reactions. A proportional-integral feedback control
      strategy based on these estimators was designed and implemented to control the
      growth rate of Candida utilis, Kluyveromyces marxianus and Pichia pastoris by
      regulating an exponential substrate feed. Maintaining a particular specific
      growth rate throughout a culture is essential for reproducible product quality in
      industrial bioprocesses and therefore a key sequence for the step from quality by
      analysis to quality by design. The potential of biocalorimetry as a reliable
      biomass monitoring tool and as a key part of a robust control strategy for
      aerobic fed-batch cultures of Crabtree-negative yeast cells in defined growth
      medium was investigated. Presenting controller errors of less than 4% in the best
      cases, the approach paves the way for the development of a generally applicable
      process analytical technology platform for monitoring and control of microbial
      fed-batch cultures.

PMID- 21845387
TI  - Effect of two routes of administration of dexamethasone on pain, edema, and
      trismus in impacted lower third molar surgery.
AB  - PURPOSE: The aim of the present study was to compare pain, edema, and trismus in
      the postoperative period following third molar surgery using 8 mg of
      dexamethasone administered either orally or through local injection. METHODS: A
      prospective, controlled, randomized trial was carried out involving 60 lower
      third molar surgeries in 67 patients between October 2008 and June 2009. The
      sample was randomly divided into three groups: group A (local injection), group B
      (tablets), and group C (control). In all cases, either ostectomy or crown
      sectioning was employed. On the second and seventh day following surgery, linear
      edema was determined using facial landmarks, and maximal mouth opening
      measurements were performed. Postoperative pain was recorded using a visual
      analog scale. RESULTS: Patient age ranged from 14 to 37 years (mean, 21.0 years).
      With regard to pain, edema, and trismus, the two administration routes tested
      (local injection and tablets) demonstrated similar efficacy, and both methods
      achieved better results in comparison to the control group. CONCLUSION: Both the
      oral administration and local injection of dexamethasone proved effective in
      reducing pain, edema, and trismus compared to control group following lower third
      molar surgeries, achieving similar results.

PMID- 21845388
TI  - Association between somatization subscale score and serotonin transporter
      availability in healthy volunteers--a single photon emission computed tomography
      study with [123I] ADAM.
AB  - RATIONALE AND OBJECTIVE: Serotonin is one of the key neuromodulators involved in
      fundamental cerebral functions and behaviors. Previous study has demonstrated
      that somatization symptoms are probably associated with central serotonergic
      circuits, which are implicated in anxiety and nociception regulation. This study
      aims to examine the correlation between somatization subscale score and serotonin
      transporter (SERT) availability in healthy volunteers. METHODS: Sixty-four
      healthy participants, 26 males and 38 females, were enrolled from the community
      and were administered the single somatization subscale of the Chinese symptom
      checklist 90 revised (SCL90-R). Single photon emission computed tomography with
      [(123)I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine was also
      performed to examine SERT availability. RESULTS: The somatization scores were
      negatively correlated with SERT availability (Spearman's rho = -0.35, p = 0.005),
      particularly in males (Spearman's rho = -0.54, p = 0.004). CONCLUSION: This
      result reconfirmed the correlation between central serotonergic activity and the
      intensity of somatization symptoms, even in healthy participants. However, a
      gender difference exists in this correlation.

PMID- 21845389
TI  - The safety of studies with intravenous Delta9-tetrahydrocannabinol in humans,
      with case histories.
AB  - RATIONALE: Delta-9-tetrahydrocannabinol (THC) is one of the few cannabinoid
      receptor ligands that can be used to probe the cannabinoid system in humans.
      Despite increasing interest in the cannabinoid receptor system, use of
      intravenous THC as a research tool has been limited by concerns about its abuse
      liability and psychoactive effects. OBJECTIVES: This study aims to evaluate the
      safety of all intravenous THC studies conducted at this center for the past 13
      years. METHODS: Included were 11 studies with 266 subjects (14 schizophrenia
      patients and 252 healthy subjects, of whom 76 were frequent cannabis users), 351
      active THC infusions, and 226 placebo infusions. Subjects were monitored for
      subjective and physical adverse events and followed up to 12 months beyond study
      participation. RESULTS: There was one serious and 70 minor adverse events in 9.7%
      of subjects and 7.4% of infusions, with 8.5% occurring after the end of the test
      day. Nausea and dizziness were the most frequent side effects. Adverse events
      were more likely to be associated with faster infusion rates (2-5 min) and higher
      doses (>2.1 mg/70 kg). Of 149 subjects on whom long-term follow-up data were
      gathered, 94% reported either no change or a reduction in their desire to use
      cannabis in the post-study period, 18% stated that their cannabis use decreased,
      and 3% stated that it increased in the post-study period. CONCLUSIONS: With
      careful subject selection and screening, risk to subjects is relatively low.
      Safeguards are generally sufficient and effective, reducing both the duration and
      severity of adverse events.

PMID- 21845391
TI  - Case of metastatic pulmonary carcinoma in optic disc diagnosed from results of
      biopsy performed during vitrectomy surgery.
AB  - BACKGROUND: Most intraocular metastatic tumors occur in the uveal tract, while
      isolated metastasis to the optic nerve is rarely found. We report a case of
      metastasis to the optic disc from primary lung cancer, diagnosed from biopsy
      findings obtained during a vitrectomy. PATIENT AND METHODS: A 69-year-old male
      presented with gradual visual impairment due to a milky white tumour that
      extended from the optic disc into the vitreous cavity. A systemic examination
      revealed primary squamous cell lung cancer. RESULTS: A biopsy specimen was
      obtained from the optic disc tumor during a vitrectomy, which led to a diagnosis
      of metastasis from lung cancer. Despite courses of chemotherapy and radiotherapy,
      the patient died of brain metastasis. DISCUSSION: There are few reports of
      secondary optic disc tumors and pathological biopsy findings are rare. When a
      milky white tumor is observed extending from the optic disc, a possible
      differential diagnosis is metastatic neoplasm.

PMID- 21845390
TI  - Effects of intravitreal bevacizumab (Avastin) on the porcine retina.
AB  - BACKGROUND: To evaluate the effects of intravitreal bevacizumab (Avastin) on the
      porcine retina, with respect to structural alterations, expression of proteins
      involved in apoptosis (bax, caspase-3, caspase-9) and gliosis (vimentin, GFAP),
      expression of factors which influence the development of vascular edema (VEGF,
      PEDF), and of membrane channels implicated in retinal osmohomeostasis (Kir4.1,
      aquaporin-1, aquaporin-4). METHODS: One eye of seven adult pigs received a single
      intravitreal injection of bevacizumab (1.25 mg). Control eyes received buffered
      saline. For light and electron microscopy, the eyes were prepared 3 (one animal)
      and 7 days (two animals) after injection. Retinal slices were immunostained
      against gliosis- and apoptosis-related proteins. The gene expression was
      determined in the neuroretina and the retinal pigment epithelium of the remaining
      four animals with real-time RT-PCR 2 days after injection of bevacizumab.
      RESULTS: Intravitreal bevacizumab did not induce alterations in the retinal
      structure, neither at light microscopic nor at electron microscopic level. The
      photoreceptors were well-preserved; no signs of photoreceptor damage or
      mitochondrial swelling were observed. Bevacizumab did also not induce reactive
      gliosis (as indicated by the unaltered immunolocalization of the glial proteins
      vimentin, GFAP, and glutamine synthetase) or apoptosis (as indicated by the
      unaltered immunolocalization of bax, caspase-3, and caspase-9). Intravitreal
      bevacizumab decreased the transcriptional expression of VEGF-A, and increased the
      expression of Kir4.1 in the neuroretina and pigment epithelium, and of PEDF in
      the pigment epithelium. Bevacizumab did not alter the transcriptional expression
      of GFAP, bax, caspase-3, VEGF receptor-1 and -2, and aquaporin-1 and -4.
      CONCLUSIONS: A single intravitreal injection of bevacizumab does not result in
      structural changes of the porcine retina, nor in induction of gliosis or
      apoptosis. The bevacizumab-induced transcriptional downregulation of VEGF and
      upregulation of Kir4.1 might protect the retina from the development of vascular
      and cytotoxic edema.

PMID- 21845392
TI  - Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus,
      postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a
      homozygous NPHP3 mutation.
AB  - We report the rare association of Caroli disease (intrahepatic bile duct ectasia
      associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia,
      situs inversus, postaxial polydactyly, and preauricular fistulas in a female
      child. She presented with end-stage renal disease at the age of 1 month, followed
      by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile
      ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined
      liver-kidney transplantation was performed at the age of 4 years, with excellent
      outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation,
      confirming that this malformation complex is a ciliopathy. CONCLUSION: This rare
      association required an exceptional therapeutic approach: combined simultaneous
      orthotopic liver and kidney transplantation in a situs inversus recipient. The
      long-term follow-up was excellent with a very good evolution of the renal and
      hepatic grafts and normalization of growth and weight. This malformation complex
      has an autosomal recessive inheritance with a 25% recurrence risk in each
      pregnancy.

PMID- 21845393
TI  - Catastrophic antiphospholipid syndrome: first signs in the neonatal period.
AB  - The term "catastrophic" antiphospholipid syndrome (CAPS) is used to define a
      subset of the antiphospholipid syndrome (APS) characterized by the clinical
      evidence of three or more organ involvement by thrombotic events in a short
      period of time and with laboratory confirmation of the presence of
      antiphospholipid antibodies. We describe a male infant first admitted at 17 days
      old for necrotizing enteritis complicated by cardiac and renal failure. Because
      of progressive renal function deterioration, a renal biopsy was performed at 8
      months old, and histopathologic examination was compatible with renal venous
      thrombosis. Laboratory searching for vascular, prothrombotic, and metabolic
      disease was negative. Five months later, he developed two different episodes (20
      day range) of ischemic stroke. Genetic test for thrombophilic conditions was
      positive for two different mutations, and repeatedly high titers of lupus
      anticoagulant, anticardiolipin, and anti-beta2glicoprotein I antibodies were
      found. He was treated successfully with anticoagulants and showed a favorable
      clinical evolution. To the best of our knowledge, this is the youngest patient
      reported with probable CAPS. Although rare, APS/CAPS in the neonatal period or in
      the first year of life must be suspected in infants presenting with thrombotic
      phenomena. The present case illustrates the importance of an early diagnosis and
      treatment to enhance possibilities of survival.

PMID- 21845396
TI  - Sagittal balance parameters influence indications for lumbar disc arthroplasty or
      ALIF.
AB  - Chronic lower back pain is a potentially incapacitating condition associated with
      disc degeneration. Although therapy is primarily pharmaceutical, surgery
      comprising arthrodesis constitutes an alternative. Anterior intersomatic lumbar
      arthrodesis (ALIF, anterior interbody lumbar fusion) is the reference approach,
      although total disc arthroplasty may also be undertaken. Analysis of pelvic and
      spinal parameters provides the best indication of sagittal balance. MATERIALS AND
      METHODS: This was a prospective study in a continuous series of 99 patients
      presenting chronic lower back pain due to disc disease. Pelvic incidence, sacral
      slope, pelvic tilt, spino-sacral angle (SSA) and the four back types in the
      Roussouly classification were studied in radiographs of the whole spine under
      load using an EOS imaging system. RESULTS: The pre-operative SSA value for the
      study population was 126.09 degrees  +/- 8.45 degrees  and the mean spine tilt
      angle was 90 degrees  compared with 95 degrees  in healthy subjects. Following
      surgery, the SSA was considerably increased in the discal arthroplasty, resulting
      in a significantly more balanced spinal position. In the group of patients
      undergoing arthrodesis using the ALIF technique, no such significant improvement
      was found despite the use of a lordosis cage. We showed that in cases of low
      pelvic incidence, it was necessary to maintain a Roussouly type 1 or 2 back
      without increasing lordosis. The results demonstrated the value of L4-L5 disc
      prostheses in these subjects. L5-S1 arthrodesis seemed a more suitable approach
      for treating patients with elevated sacral slope (back type 3 or 4). This new
      type of analysis of sagittal parameters should be performed prior to all surgical
      procedures involving lumbar prostheses.

PMID- 21845398
TI  - Effect of the erbium:yttrium-aluminum-garnet laser or diamond bur cavity
      preparation on the marginal microleakage of class V cavities restored with
      different adhesives and composite systems.
AB  - The aim of this in vitro study was to compare the microleakage of Er:YAG laser
      and diamond bur on different bonding systems in class V restorations. Class V
      cavities were prepared with Er:YAG laser or diamond bur on 80 intact human
      molars. Teeth were randomly distributed into ten groups and cavities were
      restored with CeramX duo (DENTSPLY) or Filtek Silorane (3M/ESPE) using different
      bonding materials (One Coat 7.0 (Coltene), XP Bond (DENTSPLY), Clearfil Protect
      Bond (Kuraray), AdperSE (3M/ESPE), and Silorane System Adhesive (3M/ESPE). All
      specimens were subjected to thermocycling and load cycling. After being immersed
      in silver nitrate dye, the specimens were sectioned. Microleakage was evaluated
      by stereomicroscope and SEM. Data were statistically analyzed by one-way ANOVA,
      Kruskal-Wallis, and Mann-Whitney tests. Statistically differences were found
      between groups (p > 0.05) and cavities prepared with the Er:YAG laser showed
      higher microleakage than diamond bur. The microleakage of different bonding
      systems was influenced by the choice of diamond bur or Er:YAG laser for class V
      composite cavity preparation.

PMID- 21845399
TI  - A computational model of the hippocampus that represents environmental structure
      and goal location, and guides movement.
AB  - Hippocampal place cells (PCs) are believed to represent environmental structure.
      However, it is unclear how and which brain regions represent goals and guide
      movements. Recently, another type of cells that fire around a goal was found in
      rat hippocampus (we designate these cells as goal place cells, GPCs). This
      suggests that the hippocampus is also involved in goal representation. Assuming
      that the activities of GPCs depend on the distance to a goal, we propose an
      adaptive navigation model. By monitoring the population activity of GPCs, the
      model navigates to shorten the distance to the goal. To achieve the distance
      dependent activities of GPCs, plastic connections are assumed between PCs and
      GPCs, which are modified depending on two reward-triggered activities: activity
      propagation through PC-PC network representing the topological environmental
      structure, and the activity of GPCs with different durations. The former activity
      propagation is regarded as a computational interpretation of "reverse replay"
      phenomenon found in rat hippocampus. Simulation results confirm that after
      reaching a goal only once, the model can navigate to the goal along almost the
      shortest path from arbitrary places in the environment. This indicates that the
      hippocampus might play a primary role in the representation of not only the
      environmental structure but also the goal, in addition to guiding the movement.
      This navigation strategy using the population activity of GPCs is equivalent to
      the taxis strategy, the simplest and most basic for biological systems. Our model
      is unique because this simple strategy allows the model to follow the shortest
      path in the topological map of the environment.

PMID- 21845400
TI  - The role of EMT in renal fibrosis.
AB  - It is clear that the well-described phenomenon of epithelial-mesenchymal
      transition (EMT) plays a pivotal role in embryonic development, wound healing,
      tissue regeneration, organ fibrosis and cancer progression. EMTs have been
      classified into three subtypes based on the functional consequences and biomarker
      context in which they are encountered. This review will highlight findings on
      type II EMT as a direct contributor to the kidney myofibroblast population in the
      development of renal fibrosis, specifically in diabetic nephropathy, the
      signalling molecules and the pathways involved in type II EMT and changes in the
      expression of specific miRNA with the EMT process. These findings have provided
      new insights into the activation and development of EMT during disease processes
      and may lead to possible therapeutic interventions to suppress EMTs and
      potentially reverse organ fibrosis.

PMID- 21845401
TI  - Transforming growth factor-beta signaling in tumor initiation, progression and
      therapy in breast cancer: an update.
AB  - Transforming growth factor-beta (TGF-beta) is a ubiquitous cytokine playing an
      essential role in cell proliferation, differentiation, apoptosis, adhesion and
      invasion, as well as in cellular microenvironment. In malignant diseases, TGF
      beta signaling features a growth inhibitory effect at an early stage but
      aggressive oncogenic activity at the advanced malignant state. Here, we update
      the current understanding of TGF-beta signaling in cancer development and
      progression with a focus on breast cancer. We also review the current approaches
      of TGF-beta signaling-targeted therapeutics for human malignancies.

PMID- 21845402
TI  - The analysis of receptor-binding cancer antigen expressed on SiSo cells (RCAS1)
      immunoreactivity within the microenvironment of the ovarian cancer lesion
      relative to the applied therapeutic strategy.
AB  - RCAS1 is involved in generating the suppressive profile of the tumor
      microenvironment that helps cancer cells evade immune surveillance. The status of
      the cells surrounding the cancer nest may affect both the progression of the
      cancer and the development of metastases. In cases of ovarian cancer, a large
      number of patients do not respond to the applied therapy. The patient's response
      to the applied therapy is directly linked to the status of the tumor
      microenvironment and the intensity of its suppressive profile. We analyzed the
      immunoreactivity of RCAS1 on the cells present in the ovarian cancer
      microenvironment in patients with the disease; these cells included macrophages
      and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity
      levels within these cells, taking into consideration the clinical stage of the
      cancer and the therapeutic strategy applied, such as the number of chemotherapy
      regiments, primary cytoreductive surgery, or the presence of advanced ascites. In
      the patients who did not respond to the therapy we observed significantly higher
      immunoreactivity levels of RCAS1 within the cancer nest than in those patients
      who did respond; moreover, in the non-responsive patients we found RCAS1 within
      both macrophages and carcinoma-associated fibroblasts. RCAS1 staining may provide
      information about the intensity of the immuno-suppressive microenvironment
      profile found in cases of ovarian cancer and its intensity may directly relate to
      the clinical outcome of the disease.

PMID- 21845403
TI  - Age and estrogen-based hormone therapy affect systemic and local IL-6 and IGF-1
      pathways in women.
AB  - A thorough understanding of the role of estrogens on aging-related muscle
      weakness is lacking. To clarify the molecular mechanisms underlying the effects
      of hormone replacement therapy (HRT) on skeletal muscle, we analyzed systemic
      protein and local mRNA levels of factors related to interleukin 6 (IL-6) and
      insulin-like growth factor 1 (IGF-1) pathways in 30- to 35-year-old (n = 14)
      women (without hormonal contraceptives) and in 54- to 62-year-old monozygotic
      female twin pairs discordant for HRT (n = 11 pairs, mean duration of HRT 7.3 +/-
      3.7 years). Biopsies were taken from vastus lateralis muscle and from abdominal
      adipose tissue. We found, first, that the systemic levels of IL-6 receptors sIL
      6R and sgp130 are sensitive to both age and HRT concomitant with the changes in
      body composition. The serum levels of sgp130 and sIL-6R were 16% and 52% (p <=
      0.001 for both variables) higher in postmenopausal women than in premenopausal
      women, and 10% and 9% lower (p = 0.033 and p < 0.001, respectively) in the HRT
      using than in their non using co-twins. After adjustment for body fat amount, the
      differences were no more significant. Second, the transcript analyses emphasize
      the impact of adipose tissue on systemic levels of IL-6, sgp130 and sIL6R, both
      at pre- and postmenopausal age. In muscle, the most notable changes were 28%
      lower gene expression of IGF-1 splice variant Ea (IGF-1Ea) and 40% lower
      expression of splice variant Ec (IGF-1Ec) in the postmenopausal non-users than in
      premenopausal women (p = 0.016 and 0.019, respectively), and 28% higher
      expression of IGF1-receptor in HRT users than in non-users (p = 0.060). The
      results tend to demonstrate that HRT has positive anti-catabolic effect on aging
      skeletal muscle.

PMID- 21845404
TI  - Influence of the supporting die structures on the fracture strength of all
      ceramic materials.
AB  - This study investigated the influence of the elastic modulus of supporting dies
      on the fracture strengths of all-ceramic materials used in dental crowns. Four
      different types of supporting die materials (dentin, epoxy resin, brass, and
      stainless steel) (24 per group) were prepared using a milling machine to simulate
      a mandibular molar all-ceramic core preparation. A total number of 96 zirconia
      cores were fabricated using a CAD/CAM system. The specimens were divided into two
      groups. In the first group, cores were cemented to substructures using a dual
      cure resin cement. In the second group, cores were not cemented to the supporting
      dies. The specimens were loaded using a universal testing machine at a crosshead
      speed of 0.5 mm/min until fracture occurred. Data were statistically analyzed
      using two-way analysis of variance and Tukey HSD tests (alpha = 0.05). The
      geometric models of cores and supporting die materials were developed using
      finite element method to obtain the stress distribution of the forces. Cemented
      groups showed statistically higher fracture strength values than non-cemented
      groups. While ceramic cores on stainless steel dies showed the highest fracture
      strength values, ceramic cores on dentin dies showed the lowest fracture strength
      values among the groups. The elastic modulus of the supporting die structure is a
      significant factor in determining the fracture resistance of all-ceramic crowns.
      Using supporting die structures that have a low elastic modulus may be suitable
      for fracture strength tests, in order to accurately reflect clinical conditions.

PMID- 21845405
TI  - A model program for hepatitis B vaccination and education of schoolchildren in
      rural China.
AB  - OBJECTIVES: Incomplete hepatitis B virus (HBV) vaccine coverage and poor HBV
      related knowledge in China leave millions of children unprotected from this life
      threatening infection. To address these gaps, a pilot program for HBV education
      and vaccination was launched in rural China. METHODS: In 2006, public and private
      organizations in the US and China collaborated to provide HBV education and
      vaccination to 55,000 school-age children in the remote, highly HBV-endemic area
      of Qinghai Province. The impact of the educational program on HBV-related
      knowledge was evaluated among more than 2,800 elementary school students.
      RESULTS: Between September 2006 and March 2007, the three-shot hepatitis B
      vaccine series was administered to 54,680 students, with a completion rate of
      99.4%. From low pre-existing knowledge levels, classroom educational sessions
      statistically significantly increased knowledge about HBV risks, symptoms,
      transmission, and prevention. CONCLUSIONS: This program offers an effective and
      sustainable model for HBV catch-up vaccination and education that can be
      replicated throughout China, as well as in other underserved HBV-endemic regions,
      as a strategy to reduce chronic HBV infection, liver failure, and liver cancer.

PMID- 21845406
TI  - Intersectoral action for health at a municipal level in Cuba.
AB  - OBJECTIVE: To consider how Cuba's acknowledged achievement of excellent health
      outcomes may relate to how health determinants are addressed intersectorally.
      METHODS: Our team of Canadian and Cuban researchers and health policy
      practitioners undertook a study to consider the organization and practices
      involved in addressing health determinants in 2 municipalities (1 urban and 1
      rural). The study included a questionnaire of municipal Health Council members
      and others involved in health and non-health sectors, key informant interviews of
      policy makers, focus groups in each municipality and examination of three common
      case scenarios. RESULTS: Regular engagement of different sectors and other
      agencies in addressing health determinants was quite systematic and comparable in
      both municipalities. Specific policies and organizational structures in support
      of intersectoral actions were frequently cited and illustrated in case scenarios
      that demonstrate how maintenance of regular linkages facilitates regular pursuit
      of intersectoral approaches. CONCLUSIONS: The study demonstrates the feasibility
      of examining processes of intersectoral action for health processes and suggests
      that further examination in evaluating factors such as training, particular
      practices, etc., can be a fruitful direction to pursue comparatively and with
      analytical designs.

PMID- 21845407
TI  - Seasonal features of Heterophyopsis continua metacercariae in perches,
      Lateolabrax japonicus, and infectivity to the final host.
AB  - As the second intermediate host, the perch Lateolabrax japonicus provides
      metacercariae of Heterophyopsis continua to man. Fry of the perch arrive at and
      grow to mid-sized fish in the brackish water of Jinju Bay, South Korea. The H.
      continua metacercariae occur in perch as small and mid-sized forms in July and
      grow to the large form by August. The size distribution of metacercariae shifts
      dominantly to the large form in September and then remains as it was. Adult H.
      continua recovery was high from experimental chicks infected with the medium and
      large metacercariae collected in September and reduced to half from the chicks
      infected with those of October. Collectively, the H. continua metacercariae grew
      to the large form in about 20 days and achieved infectivity to chicks after 2
      months in the perches.

PMID- 21845408
TI  - Ultrastructural insights into morphology and reproductive mode of Blastocystis
      hominis.
AB  - To understand well the morphology and reproductive mode of Blastocystis hominis,
      with the help of transmission electron microscopy and scanning electron
      microscopy the ultrastructural details of B. hominis from fresh diarrheal
      specimens and cultured strains were observed. In both fecal samples and culture
      conditions, there were vacuolar and granular forms. In diarrhea, it exists in
      multivacuolar, avacuolar, and amoeboid forms. In the in vitro culture, vacuolar
      form could transform to granular form. The most commonly noticed structure on the
      cell surface was surface coat with diversity in appearance (the funiform,
      lamellar, filiform, and floccose in different thickness) and distributions. Three
      modes of reproduction were confirmed, they were binary fission, plasmotomy, and
      budding. Under the impact of host's response, the ultrastructures of surface
      coat, nucleus, and mitochondrion-like organelle sometimes changed.

PMID- 21845409
TI  - Efficacy of Eimeria tenella rhomboid-like protein as a subunit vaccine in
      protective immunity against homologous challenge.
AB  - The immune responses and protective efficacy against homologous challenge in
      chickens elicited by recombinant proteins of a rhomboid-like gene (ETRHO1) from
      Eimeria tenella was investigated in the present study. When chickens were
      immunized with the recombinant rhomboid antigen, specific antibody was generated
      by ELISA assay. In comparison with the PBS group, the expression levels of
      interleukin-2, interferon-gamma, as well as the percentages of CD4+ and CD8+
      cells in the group immunized with the recombinant rhomboid proteins were
      significantly increased (p < 0.01, p < 0.05, and p < 0.05, respectively). These
      results suggest that rhomboid was capable of eliciting humoral and cell-mediated
      immunity response in birds. Challenge experiments demonstrated that the
      recombinant rhomboid protein could provide chickens with a protection rate around
      77.3%. Numbers of oocysts and cecal lesion from chickens in the group immunized
      with recombinant rhomboid proteins decreased significantly, and the body weight
      increased significantly when compared with chickens in the PBS group (p < 0.05).
      These results suggested that the recombinant rhomboid antigen was able to impart
      partial protection against homologous challenge in chicken and could be a
      potential candidate for an E. tenella vaccine development.

PMID- 21845410
TI  - First record of anisakid juveniles (Nematoda) in the European seabass
      Dicentrarchus labrax (family: Moronidae), and their role as bio-indicators of
      heavy metal pollution.
AB  - This study assessed the anisakid nematode distribution pattern in the fish
      collected from coasts of Mediterranean Sea, Egypt, during the period September
      2010-April 2011. Two hundred thirty out of 300 (76.7%) Dicentrarchus labrax
      (European seabass) marine fishes belonging to family Moronidae were dissected and
      found to be infected with larva three nematodes. The larvae had been studied by
      light and scanning electron microscopy. The present work represents the first
      record of the presence of the parasite in this fish in the Mediterranean Sea. The
      concentrations of some heavy metals (Pb, Zn, Fe, Cd, Cu, Mn, Ni) in parasites as
      well as in tissues of fish were measured. The presented results showed that the
      nematode parasites are able to accumulate heavy metals in their tissues and in
      some cases that they are able to accumulate large amounts of heavy metals in a
      higher amount than host tissues. This demonstrated their sustainability as
      bioindicators of environmental pollution by removing heavy metals and help in the
      survival of fish.

PMID- 21845411
TI  - Anthelmintic effect of Mentha spp. essential oils on Echinococcus granulosus
      protoscoleces and metacestodes.
AB  - The aim of the present work was to determine the in vitro effect of Mentha
      piperita and Mentha pulegium essential oils against Echinococcus granulosus and
      to compare the effectiveness of both oils according to the exposure time and
      concentration. Although both treatments had a protoscolicidal effect, M. pulegium
      had a considerably stronger effect than M. piperita. Essential oil of M. pulegium
      produced dose- and time-dependent effects. Maximal protoscolicidal effect was
      observed after 12 days of incubation and reached 0% after 18 days. This lack of
      viability was proved during the determination of infectivity into mice. Essential
      oil of M. piperita produced only a time-dependent effect. At 24 days p.i., the
      viability of protoscoleces decreased to approximately 50%. Scanning and
      transmission electron microscopy (SEM and TEM) demonstrated the drug-induced
      ultrastructural damage. On the other hand, a loss of turgidity was detected in
      all M. pulegium-treated cysts respective of the drug concentration. There was a
      correlation between the intensity of damage and the concentration of the
      essential oil assayed. Studies by SEM revealed that the germinal layer of treated
      cysts lost the feature multicellular structure. M. pulegium essential oil showed
      piperitone oxide as main compound in their composition, and we suggest that this
      component could be responsible of the markedly anthelmintic effect detected. Our
      data suggest that essential oils of Mentha spp. can be a promising source of
      potential protoscolicidal agents. The isolation of active anthelmintic
      constituents is in progress and may lead to the discovery of compounds with
      improved therapeutic value.

PMID- 21845412
TI  - Description of Sarcocystis anasi sp. nov. and Sarcocystis albifronsi sp. nov. in
      birds of the order Anseriformes.
AB  - On the basis of the already published morphological, 18S rDNA, 28S rDNA data
      (Kutkiene et al., Parasitol Res 99:562-565, 2006; Parasitol Res 102:691-696,
      2008; Parasitol Res 104:329-336, 2009), and ITS-1 region investigation results of
      sarcocysts presented in this paper, Sarcocystis albifronsi sp. nov. from the
      white-fronted goose (Anser albifrons) and Sarcocystis anasi sp. nov. from the
      mallard duck (Anas platyrhynchos) are described.

PMID- 21845413
TI  - Enantiomerical pharmacokinetic prevalence of (+) albendazole sulphoxide in
      Trichinella spiralis muscle larvae.
AB  - In a previous work, it was demonstrated that (+) albendazole sulphoxide (SOABZ)
      has higher anthelmintic activity than (-) SOABZ (Bolas-Fernandez et al. J
      Parasitol 90:407-409, 2004). In this work, the pharmacokinetics characteristics
      of SOABZ and its enantiomeric forms were studied in an ex vivo model system for
      Trichinella spiralis isolated muscle larvae. To this end, samples of either
      racemic or purified SOABZ enantiomers were added to the incubation medium.
      Quantification of either albendazole, racemic SOABZ or its enantiomers was
      performed by validated HPLC methods and the effect of different SOABZ
      concentrations in relation to time of contact with the larvae was also analysed.
      Obviously, higher concentration of SOABZ in the medium leads to higher
      concentrations of SOABZ inside the larvae which increased in an exponential mode,
      thus indicating a simple diffusion process. At least 18 h of contact with the
      drug was required to achieve anthelmintic effects. Besides, after this time, the
      concentration of (+) SOABZ inside the larvae was significantly higher than that
      of the (-) SOABZ. From these results, it can be concluded that the higher
      activity found in the previous work is clearly related to the pharmacokinetic
      prevalence of (+) enantiomer inside the larvae.

PMID- 21845415
TI  - [Seeing sounds? The visualization of acoustic phenomena in heart diagnostics].
AB  - During the nineteenth century physiologists and clinicians developed several
      graphical recording systems for the mechanical registration of heart sounds.
      However, none of these replaced traditional methods of auscultation. The paper
      describes criticism of the aural sense as one of the driving forces behind the
      development of phonocardiography and analyses its variants from a technological
      and clinical perspective. Against the background of the physiological "method of
      curves," the parameters that prevented the implementation of phonocardiography
      against overwhelming odds are highlighted. Contemporaries denied specific
      evidence beyond auscultation. Many clinicians also feared that the art of
      auscultation was being undermined by the new, reproducible mechanical methods.
      The paper argues that phonocardiography was on the one hand regarded as
      impractical in clinical settings; on the other hand-and even more important
      implicit practices, tacit knowledge and cultural models fostered skepticism
      against the new method. The argument of "self-evidence"-often connected to
      medical images, curves, graphs or tables-was not valid for the visualization of
      cardiac sounds in the opinion of the promoters of acoustic heart sound
      registration and its individual interpretation. Rather, the acts of subjective
      hearing and objectively reporting what was heard seemed "self-evident" for
      pathophysiological characteristics and the development of a diagnosis. Therefore,
      auscultation and phonocardiography coexisted with different emphases. While
      auscultation remained the method of choice for a bedside diagnosis,
      phonocardiography played its role in differential diagnostics or research
      settings.

PMID- 21845414
TI  - Cellular immune responses in Echinostoma caproni experimentally infected mice.
AB  - The Echinostoma caproni-mice system is extensively used as an experimental model
      for the study of the factors involved in the establishment of chronic intestinal
      helminth infections. Although several parameters of the immunobiology of the host
      parasite system have been studied in detail, the current knowledge of the
      cellular responses in these infections is still scarce. In the present paper, we
      analyze the kinetics of the circulating CD3(+) and CD19(+) cell populations and
      the different T-cell phenotype profiles in mice experimentally infected with E.
      caproni. Whereas the CD3(+) populations remained stable during the complete
      experiment, a marked increase in CD19(+) cells was observed from 4 weeks post
      infection and beyond. Similarly, a marked increase in CD8(+) cell populations was
      observed in the 2 week post-infection. Our results show that E. caproni infection
      in mice alters the peripheral lymphoid cell populations, which may be important
      to determine the course of the infection. In this sense, CD8(+) cells can be
      essential in relation to their role as a source of IFN-gamma.

PMID- 21845416
TI  - Hepatoid adenocarcinoma of the transverse colon.

PMID- 21845417
TI  - Colorectal carcinoma in different age groups : a histopathological analysis.
AB  - PURPOSE: Although colorectal cancer is typical in the older population, tumor
      onset before age 40 is not infrequent. However, the behavior, characteristics,
      and prognosis of this disease in young patients are unclear when compared to the
      older population. It is believed that young patients have a poor prognosis. We
      hypothesized that young patients have a poor prognosis because they have advanced
      stage cancer with more aggressive pathologic features. METHODS: Using a
      university hospital database, we analyzed the histopathological features of three
      groups of patients with a diagnosis of colorectal cancer: young age group
      (patients 40 years and younger), intermediate age group (patients 41-80 years
      old), and old age group (patients 81 years and older). RESULTS: A total of 653
      cases of colorectal cancer were analyzed. The young age group comprised 48
      patients (7.4%), the intermediate age group comprised 538 patients (82.4%) and
      the old age group consisted of 67 patients (10.3%).The gender distribution was
      similar between the groups. The mean age of the young, intermediate, and old age
      groups were 34.5 (+/-5.0), 61.7 (+/-11.1) and 85.1 (+/-4.6) years old,
      respectively. The pathological features analyzed such as lymph node involvement,
      tumor histological classification and grade, venous, neural and lymphatic
      invasion, T and N classification of the TNM System, and Astler-Coller
      classification were similar between the age groups. CONCLUSIONS: The colorectal
      histopathological features in young patients are similar to older patients. More
      aggressive characteristics or more advanced stage are not seen in younger
      patients.

PMID- 21845418
TI  - Postoperative complications after closure of a diverting ileostoma--differences
      according to closure technique.
AB  - PURPOSE: The aim of this study was to compare three methods for closure of a
      diverting ileostoma according to development of postoperative small-bowel
      obstruction (SBO) and anastomotic leakage (AL). METHODS: Complications arising
      within 30 days after closure of a defunctioning loop ileostomy in 351 patients
      during the period 1999-2006 were studied retrospectively by evaluation of case
      records. The techniques employed were: hand-sewn anastomosis without bowel
      resection, hand-sewn anastomosis with bowel resection and stapled anastomosis.
      RESULTS: Of the 351 patients, 149 had a hand-sewn anastomosis without bowel
      resection (HS), 70 had a hand-sewn anastomosis with bowel resection (HSR) and 132
      patients had a stapled anastomosis (S). The total number of SBOs was 44 patients
      (12.5%). In the two hand-sewn groups, 15.5% (34 patients) suffered postoperative
      SBO compared to 7.6% (10 patients) in the stapled group (p = 0.029). No
      difference in AL could be found between the groups, where the overall frequency
      was 2.8% (10 patients). Median hospital stay was 6 days in the HS group, 5 days
      in the HSR group and 4 days in the S group (p = 0.001). CONCLUSION: In the
      present study, stapled anastomosis was associated with a lower frequency of
      postoperative SBO and a shorter hospital stay compared to sutured anastomosis
      (either with or without a short small-bowel resection) after closure of a
      diverting ileostoma.

PMID- 21845419
TI  - Another Hb with inclusion bodies beta-thalassemia, owing to Hb Durham-N.C.
      [beta114(G16) Leu > Pro]. First case described in Hispanic populations.

PMID- 21845420
TI  - The role of radiotherapy in endometrial cancer: current evidence and trends.
AB  - Adjuvant treatment of patients with endometrial cancer is tailored to clinical
      pathological prognostic factors. Pelvic radiation therapy for stage I endometrial
      cancer (EC) provides a highly significant improvement of local control, but
      without survival advantage. Low-risk EC patients have a very favorable prognosis,
      and should be observed after surgery. Use of adjuvant radiotherapy (RT) is
      limited to patients with high-intermediate or high-risk factors. For those with
      high-intermediate risk features, vaginal brachytherapy alone provides excellent
      vaginal control with less morbidity and better quality of life than pelvic
      external beam RT (EBRT). For patients with stage I-III EC with high-risk
      features, the use of adjuvant chemotherapy alone has not shown survival benefit
      as compared to pelvic EBRT. A first trial comparing pelvic EBRT with or without
      adjuvant chemotherapy has shown better progression-free survival with combined
      therapy. Current ongoing trials are exploring the role of combined RT and
      chemotherapy, compared to chemotherapy or RT alone.

PMID- 21845421
TI  - Ongoing development of monoclonal antibodies and antibody drug-conjugates in
      lymphoma.
AB  - Rituximab, a monoclonal antibody (mAb) directed against CD20, has changed
      practices in the treatment of patients with B-cell lymphoma. The large success of
      rituximab has contributed to validate immunotherapy with monoclonal antibodies as
      a valuable strategy in lymphoma. Recently, better-engineered anti-CD20-mAbs have
      been designed to improve efficacy and safety. Also, new antibodies targeting
      other lymphoma subtypes including T-cell lymphoma and Hodgkin's disease have been
      developed. Ongoing pharmacology development is concentrating on immuno-drug
      conjugates combining the toxicity of chemotherapy, isotopes, or toxins with the
      specificity of mAbs. This article offers an overview on the development of new
      antibodies and immuno conjugates in lymphoma.

PMID- 21845422
TI  - [Photodynamic diagnostics of bladder carcinoma].
AB  - The question whether conventional cystoscopy should always be performed together
      with fluorescent diagnostic procedures remains to be answered. The current
      article presents the current literature dealing with this topic. Particularly for
      relevant carcinoma in situ lesions of the bladder there is no obvious advantage
      for photodynamic diagnostics compared to conventional cystoscopy with consistent
      use of urine cytology.

PMID- 21845423
TI  - [Renal masses in pregnancy. Diagnostics and therapeutic management].
AB  - Cancer is the second most common cause of death in women of childbearing age.
      However, renal cell carcinoma (RCC) is a rare tumor in this collective with an
      incidence far below 5/100,000 cases per year. Therefore, medical experience with
      respect to diagnostics and therapeutic management of newly diagnosed RCC in
      pregnant women is scarce and the number of published cases low. However, recent
      studies indicated that higher estrogen levels and multigravidity could be
      associated with a higher risk of RCC. The aim of this article is to summarize the
      clinical experience in treating pregnant women with renal cancer against the
      background of those cases published in the literature.

PMID- 21845424
TI  - [Incidence and long-term prognosis of papillary renal cancer. Results of a
      retrospective multicenter study].
AB  - OBJECTIVES: Papillary renal cell carcinoma (pRCC) represents the largest subgroup
      of non-clear-cell kidney cancer. In this retrospective multicenter study, we
      assessed tumor characteristics and long-term prognosis of patients with pRCC in
      comparison with conventional clear-cell cancer (ccRCC). METHODS: We evaluated
      2,804 patients who had undergone renal surgery for pRCC or ccRCC between 1990 and
      2006. The mean follow-up was 65 months. RESULTS: Both pRCC and ccRCC groups were
      comparable concerning age, tumor grade and the incidence of regional lymph node
      metastasis at diagnosis. The percentage of male patients was higher in pRCC than
      in ccRCC (76.0% vs. 63.6%), pRCC patients suffered less often from advanced
      tumors (22.3% vs. 38.1%), visceral metastasis at diagnosis (8.1% vs. 14.5%) and
      died less frequently due to RCC progression (16.3% vs. 29.6%). Applying
      multivariable analyses pRCC was found to be an independent predictor of a
      favorable clinical course for patients with organ-confined RCC. In contrast in
      advanced disease papillary histology was significantly associated with a poor
      prognosis and early tumour-related death. CONCLUSIONS: pRCC seem to be stratified
      into two different prognostic groups. Localized pRCC has a significantly better
      prognosis than ccRCC. In contrast, advanced pRCC is characterized by a worse
      clinical outcome. Whether these two different pRCC cohorts are consistent with
      the recently defined types 1 and 2 pRCC subtypes or are characterized by other
      typical genetic alterations, which would lead to a novel pRCC subclassification
      is currently under investigation within the German Renal Cancer Network.

PMID- 21845425
TI  - [High-dose chemotherapy and residual tumor resection in male germ cell tumors].
AB  - As a consequence of the unsatisfactory results of conventional dose salvage
      regimens, in particular for patients with poor prognostic features at the time of
      relapse or in patients with refractory disease, high-dose chemotherapy (HDCT) was
      introduced into clinical practice in the late 1980s. The combination of
      carboplatin and etoposide (CE) still remains the backbone of most high-dose
      regimens. Multiple modifications with more dose escalations or addition of
      further drugs have been explored, most often with increased toxicity. With
      improved expertise in supportive care and the use of peripheral blood stem cells,
      hematopoetic recovery has been significantly shortened and the initial high
      treatment-related mortality reduced from more than 10% to about 3%. Since the
      incorporation of HDCT, even patients with unfavorable prognostic features or
      patients with second or subsequent relapses can achieve long-term remission.
      Following HDCT residual tumor resection plays a major role in achieving these
      long-term results. The proportion of vital residual tumor after HDCT is much
      higher than in patients after conventional chemotherapy. The role of HDCT remains
      controversial particularly as a first-line treatment and less so in the first
      salvage setting. As these patients are rare HDCT and residual tumor resection
      should only be be provided by high-volume centers with sufficient expertise in
      performing these complex procedures.

PMID- 21845426
TI  - [Ischemic testicular necrosis following vasectomy: rare and typical complications
      of an outpatient procedure].
AB  - Taking the clinical case of a patient who developed unilateral testicular
      necrosis following vasectomy as a starting point, the early and late
      complications of this procedure are described based on a literature review.In the
      USA 7% of all men undergo vasectomy, as compared to 2% in Germany. Early
      postoperative complications include bleeding/hematoma (0.5-18%), infection (0.3
      32.9%), epididymitis (0.4-6.1%), granuloma (0.07-90%), and rare complications
      such as vas deferens abscess, vesicular gland abscess, vasovenous fistula,
      testicular necrosis, arteriovenous fistula, pulmonary embolism, endocarditis,
      scrotal skin necrosis and Fournier's disease which mostly have been reported in
      the form of case reports. Late complications are chronic pain (0.5-18%), pain
      during sex (2.9%), hydrocele (0-4%) as well as spermatocele (1.6%). There is a
      failure rate of 4.3-16% as concluded from the number of patients with nonmotile
      sperm in the post-vasectomy semen analysis. The postoperative paternity rate is 0
      4%.Bilateral vasectomy is a secure way of contraception; perioperative and late
      complications are on an average rare, however, with a range up to 90%. In
      individual cases severe complications occur, which should be detected at an early
      stage. Therefore a close follow-up should be maintained after this outpatient
      procedure. One should ask for risk factors of endocarditis or thrombosis
      preoperatively. The patient should be informed of the possible loss of a testicle
      because of the severity of this complication. Postoperative semen analysis is
      obligatory.

PMID- 21845427
TI  - [German Urological Associations under National Socialism].
AB  - The Deutsche Gesellschaft fur Urologie (German Urological Association),
      established in 1907, was a German-Austrian medical society in which Jewish
      physicians held important positions. When the Nazis seized power in 1933, the
      Austrian Hans Rubritius was president of the society. The non-German presidency
      and the exclusion of Jewish colleagues from the professional society and medical
      practice led to a halt of the society's activities. At the same time in the mid
      1930s, German urologists founded the Gesellschaft Reichsdeutscher Urologen
      (Association of Reichs-German Urologists) whose members aligned themselves with
      Nazi health policies and in turn received professional and personal benefits.

PMID- 21845428
TI  - Evaluation of the MTHFR A1298C variant in leukoaraiosis.
AB  - Vascular demyelinization of the white matter of the brain is referred to as
      leukoaraiosis (LA). This very frequent entity is associated with a cognitive
      decline, thereby resulting in a deteriorating quality of life. Besides poorly
      controlled hypertension and aging, its development is reported to be associated
      with an elevated serum homocysteine level. Although the methylenetetrahydrofolate
      reductase (MTHFR) C677T genetic variant is associated with an elevated serum
      homocysteine level, it has not been proved to be an independent risk factor for
      LA. The aim of the present study was to examine whether the MTHFR A1298C genetic
      variant, which is also believed to be unfavorable, is associated with the
      presence of LA. The clinical and genetic data on 198 LA patients and 235
      neuroimaging alteration-free controls were analyzed. The presence of the A1298C
      or the 1298CC variant was calculated to be a risk factor for LA, as compared with
      the absence of both of them. The clustering of the heterozygous A1298C and C677T
      variants was proved to involve the risk of LA. Our results suggest that the MTHFR
      A1298C variant confers an independent genetic risk of LA, and this pathological
      role may be amplified by the MTHFR C677T variant.

PMID- 21845429
TI  - A lipoxin A4 analog ameliorates blood-brain barrier dysfunction and reduces MMP-9
      expression in a rat model of focal cerebral ischemia-reperfusion injury.
AB  - LXA(4) methyl ester (LXA(4)ME), a lipoxin A(4) analog, reduces ischemic insult in
      the rat models of transient or permanent cerebral ischemic injury. We
      investigated whether LXA(4)ME could ameliorate blood-brain barrier (BBB)
      dysfunction after stroke by reducing matrix metalloproteinase (MMP)-9 expression.
      Adult male rats were subjected to 2-h middle cerebral artery occlusion (MCAO)
      followed by 24-h reperfusion. Brain infarctions were detected by
      triphenyltetrazolium chloride (TTC) staining. BBB dysfunction was determined by
      examining brain edema and Evans Blue extravasation. Temporal expression of MMP-9
      was determined by zymography and Western blot. The presence of tissue inhibitors
      of metalloproteinase-1 (TIMP-1) was also determined by Western blot in tissue
      protein sample. Brain edema and Evans Blue leakage were significantly reduced
      after stroke in the LXA(4)ME group and were associated with reduced brain infarct
      volumes. MMP-9 activity and expression were inhibited by LXA(4)ME after stroke.
      In addition, LXA(4)ME significantly increased TIMP-1 protein levels. Our results
      indicate that LXA(4)ME reduces brain injury by improving BBB function in a rat
      model of MCAO, and that a relationship exists between BBB permeability and MMP-9
      expression following ischemic insult. Furthermore, these results suggest that
      LXA(4)ME-mediated reduction of MMP-9 following stroke are attributed to increased
      TIMP-1 expression.

PMID- 21845430
TI  - A novel mutation in CACNA1S gene associated with hypokalemic periodic paralysis
      which has a gender difference in the penetrance.
AB  - Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder
      characterized by periodic attacks of muscle weakness associated with a decrease
      in the serum potassium level. Several mutations in the skeletal muscle calcium
      channel alpha-subunit gene CACNA1S have been documented to be causative for
      HypoPP, but mutations in other genes have also been implicated in HypoPP. To
      further reveal the genetic causes of HypoPP, we genotyped members of a five
      generational Chinese family with HypoPP patients and identified a novel His916Gln
      mutation in all male HypoPP patients of the family. Clinical analysis
      demonstrated that the penetrance of the mutation was complete in male carriers,
      but we did not find evident clinical features in female carriers. This study
      expanded the spectrum of CACNA1S mutations associated with HypoPP and
      demonstrated a gender difference in the penetrance of the disease.

PMID- 21845432
TI  - Tissue expression of Toll-like receptors 2 and 4 in sporadic human colorectal
      cancer.
AB  - BACKGROUND: Toll-like receptors (TLRs) play an important role in innate immunity
      by sensing a variety of pathogens and inducing acquired immunity. To test our
      hypothesis that dysregulation of innate immune responses acts to trigger
      carcinogenesis, we studied the expression of TLR2 and 4 in sporadic human
      colorectal cancer tissue. METHODS: In specimens of cancerous and noncancerous
      colorectal tissue obtained at surgery, mRNA expression levels of TLR2 and 4 were
      quantified by TaqMan real-time polymerase chain reaction and compared between the
      two types of tissue. To confirm TLR2 and TLR4 protein expression levels,
      immunohistochemical analysis was performed using the same samples. RESULTS: TLR2
      mRNA expression was significantly higher in cancerous tissue than in noncancerous
      tissue, while TLR4 mRNA expression did not differ significantly.
      Immunohistochemical analysis revealed stronger staining for TLR2 in cancerous
      mucosal epithelial cells than in noncancerous tissue. Staining for TLR4 in the
      lamina propria of the mucosa was equally weakly positive in noncancerous tissue
      and cancerous tissue. This TLR-specific difference in expression suggested that
      such expression does not only reflect a local inflammatory response to cancer
      infiltration, i.e., if this was the case, both TLR2 and 4 expression would
      probably be up-regulated. Our results suggest that TLR2 expression might be
      involved in sporadic colorectal carcinogenesis, whereas TLR4 is not.

PMID- 21845433
TI  - New synthesis--duplicated genes in the ecological interactions of plants with
      their environment.

PMID- 21845431
TI  - Endothelium--role in regulation of coagulation and inflammation.
AB  - By its strategic position at the interface between blood and tissues, endothelial
      cells control blood fluidity and continued tissue perfusion while simultaneously
      they direct inflammatory cells to areas in need of defense or repair. The
      endothelial response depends on specific tissue needs and adapts to local
      stresses. Endothelial cells counteract coagulation by providing tissue factor and
      thrombin inhibitors and receptors for protein C activation. The receptor PAR-1 is
      differentially activated by thrombin and the activated protein C/EPCR complex,
      resulting in antithrombotic and anti-inflammatory effects. Thrombin and
      vasoactive agents release von Willebrand factor as ultra-large platelet-binding
      multimers, which are cleaved by ADAMTS13. Platelets can also facilitate leukocyte
      endothelium interaction. Platelet activation is prevented by nitric oxide,
      prostacyclin, and exonucleotidases. Thrombin-cleaved ADAMTS18 induces
      disintegration of platelet aggregates while tissue-type plasminogen activator
      initiates fibrinolysis. Fibrin and products of platelets and inflammatory cells
      modulate the angiogenic response of endothelial cells and contribute to tissue
      repair.

PMID- 21845434
TI  - Genetic variation of lodgepole pine, Pinus contorta var. latifolia, chemical and
      physical defenses that affect mountain pine beetle, Dendroctonus ponderosae,
      attack and tree mortality.
AB  - Plant secondary chemistry is determined by both genetic and environmental
      factors, and while large intraspecific variation in secondary chemistry has been
      reported frequently, the levels of genetic variation of many secondary
      metabolites in forest trees in the context of potential resistance against pests
      have been rarely investigated. We examined the effect of tree genotype and
      environment/site on the variation in defensive secondary chemistry of lodgepole
      pine, Pinus contorta var. latifolia, against the fungus, Grosmannia clavigera
      (formerly known as Ophiostoma clavigerum), associated with the mountain pine
      beetle, Dendroctonus ponderosae. Terpenoids were analyzed in phloem samples from
      887, 20-yr-old trees originating from 45 half-sibling families planted at two
      sites. Samples were collected both pre- and post-inoculation with G. clavigera.
      Significant variation in constitutive and induced terpenoid compounds was
      attributed to differences among families. The response to the challenge
      inoculation with G. clavigera was strong for some individual compounds, but
      primarily for monoterpenoids. Environment (site) also had a significant effect on
      the accumulation of some compounds, whereas for others, no significant
      environmental effect occurred. However, for a few compounds significant family x
      environment interactions were found. These results suggest that P. c. latifolia
      secondary chemistry is under strong genetic control, but the effects depend on
      the individual compounds and whether or not they are expressed constitutively or
      following induction.

PMID- 21845435
TI  - Squatting test: a dynamic postural manoeuvre to study baroreflex sensitivity.
AB  - INTRODUCTION: Squatting is an active posture test that can be used to assess
      baroreflex sensitivity. Indeed, the shift from squatting to standing imposes a
      major orthostatic stress leading to rapid and large changes in arterial blood
      pressure (BP) and heart rate (HR) allowing precise baroreflex assessment.
      MATERIAL AND METHODS: BP and HR can be continuously and non-invasively monitored
      with a Finapres device. RESULTS: The standing to squatting transition is
      accompanied by rises in BP, pulse pressure and cardiac output, mainly due to
      increased venous return, and by a secondary reduction in HR. Conversely, the
      squatting to standing transition is associated with an immediate drop in BP and
      both reflex tachycardia and vasoconstriction. This mirror changes in BP and HR,
      mimicking those observed with the classical pharmacological approach using
      vasopressor/vasodilating agents, allows the calculation of the so-called
      baroreflex gain. DISCUSSION: The present review describes the haemodynamic
      changes occurring in normal subjects during the shifts from standing to squatting
      and from squatting to standing and discusses the underlying cardiovascular and
      autonomic mechanisms. CONCLUSION: This careful analysis in healthy individuals
      should help in the understanding of disturbances that may be observed in patients
      with autonomic dysfunction, such as in diabetic patients with cardiovascular
      autonomic neuropathy.

PMID- 21845436
TI  - The musculocutaneous infrahyoid flap: surgical key points.
AB  - For the first time in 1979, it was described by Wang that the infrahyoid
      musculocutaneous flap (IHMC flap) appears to be extremely suitable for medium
      sized head and neck defect. Nevertheless, this flap remains unpopular because of
      its pretended lack of reliability. The aim of this study is to describe the
      surgical key points and to expose its main advantages. An IHMC flap was achieved
      on 32 patients to repair tissue loss due to surgical resection of a squamous cell
      carcinoma of the upper aero-digestive tract, from March 2006 to January 2010.
      Medical records of each of these patients were retrospectively analysed by the
      investigators including the detailed clinical, pathological and operative
      reports. No patient presented with total flap necrosis. However, we experienced
      four skin paddles necrosis. In two cases, the necrosis was total and in two cases
      partial. All donor sites were closed primarily without any tension. One patient
      showed a major dehiscence of the neck skin incision that required a pectoralis
      major flap. The IHMC flap is reliable and the harvesting technique is simple when
      the surgical key points are respected. Its advantages make it a convenient flap
      for medium-sized head and neck defect.

PMID- 21845437
TI  - Cushion bearings versus large diameter head metal-on-metal bearings in total hip
      arthroplasty: a short-term metal ion study.
AB  - INTRODUCTION: Metal-on-metal total hip arthroplasty (MOM THA) has the advantage
      of replicating the femoral head size, but the postoperative elevation of serum
      metal ion levels is a cause for concern. Metal-on-polycarbonate-urethane is a new
      cushion bearing featuring a large diameter metal head coupled with a
      polycarbonate-urethane liner. AIM: The aim of this study was to assess and
      compare serum cobalt (Co) and chromium (Cr) levels in a group of 15 patients
      treated with a cushion bearing THA system (Group A) and a group of 15 patients
      treated with a MOM THA system (Group B) at short-term. At a mean follow-up of
      27.3 months (18-35 months), in Group A the median Cr and Co serum levels were
      significantly lower than in Group B, measuring 0.24 MUg/L (0.1-2.1 MUg/L) and 0.6
      MUg/L (0.29-2.3 MUg/L) compared to 1.3 MUg/L (0.1-9 MUg/L, p < 0.001) and 2.9
      MUg/L (0.85-13.8 MUg/L, p < 0.001) respectively. RESULTS: All patients
      demonstrated an excellent clinical result, as shown by the Harris and Oxford hip
      scores. The cushion bearing THA studied in this paper showed clinical outcomes
      similar to the MOM THA bearing, with the advantage of no significant metal ion
      elevation in the serum. CONCLUSION: These findings warrant the continued clinical
      study of compliant bearing options.

PMID- 21845438
TI  - Efficacy and safety of CHG regimen (low-dose cytarabine, homoharringtonine with G
      CSF priming) as induction chemotherapy for elderly patients with high-risk MDS or
      AML transformed from MDS.
AB  - BACKGROUND: To evaluate the efficacy and toxicity of CHG regimen (low-dose
      cytarabine, homoharringtonine with G-CSF priming) as an induction chemotherapy
      for elderly patients with high-risk MDS or acute myeloid leukemia transformed
      from MDS (MDS-AML). METHODS: Thirty-three untreated patients (21 high-risk MDS
      and 12 MDS-AML) were enrolled in this study. Each patient was administered with
      the CHG regimen comprised of low-dose cytarabine (25 mg/day, days 1-14) and
      homoharringtonine (1 mg/day, days 1-14) by intravenous continuous infusion in
      combination with G-CSF (300 MUg/day) by subcutaneous injection from day 0 until
      neutrophil count recovery to 2.0 * 10(9)/L. RESULTS: The overall response rate
      (OR) was 66.7% after one course of the CHG regimen with 19 patients reaching CR
      (57.6%) and 3 patients reaching partial remission (PR) (9.1%). The median overall
      survival (OS) was 15.0 months. Patients with normal serum lactate dehydrogenase
      (LDH) appeared longer median OS when compared to patients with high LDH level (18
      months vs. 5 months, P = 0.011). Grade 3/4 thrombocytopenia occurred in 28% of
      patients, neutropenia in 34%. No treatment-related deaths occurred during the
      induction therapy. CONCLUSIONS: These data suggest that the CHG priming regimen
      is effective and safe as a novel induction therapy for elderly patients with high
      risk MDS and MDS-AML. The results need to be conformed in further study involving
      a larger cohort of patients.

PMID- 21845441
TI  - Validation of reference genes for estimating wound age in contused rat skeletal
      muscle by quantitative real-time PCR.
AB  - Gene expression profiling by quantitative real-time PCR (RT-qPCR) is a valuable
      tool in forensic science for estimating the age of a wound. To accurately assess
      gene expression levels over time in injured tissue, the genes used as internal
      reference standards must be carefully validated for transcriptional stability.
      This study examined the transcriptional stability of nine potential reference
      genes (beta-actin, GAPDH, RPL32, PGK1, SDHA, RPL13, HPRT, Tbp, and Ywhaz) in
      contused rat skeletal muscle by RT-qPCR. The raw Ct values were determined for
      each candidate gene at different time points following contusion, and the data
      were analyzed by the NormFinder, geNorm, and BestKeeper validation programs. The
      reference genes RPL13 and RPL32 were the most stably expressed genes in contused
      skeletal muscle, whereas PGK1 was the least stable. The commonly used reference
      genes beta-actin and GAPDH appeared to be too unstable for normalization of RT
      qPCR expression profiling in contused muscle. The reference genes RPL13 and RPL32
      were also the best combination for multianalysis. The use of RPL13 and RPL32 as
      internal standards may improve the accuracy of gene expression studies aimed at
      determining the age of early wounds in forensic investigations.

PMID- 21845440
TI  - Lipid metabolism modulation by the P2X7 receptor in the immune system and during
      the course of infection: new insights into the old view.
AB  - For decades, scientists have described numerous protein pathways and functions.
      Much of a protein's function depends on its interactions with different partners,
      and those partners can change depending on the cell type or system. The P2X7
      receptor (P2X7R) is one such multifunctional protein that is related to multiple
      partners and signaling pathways. The relationship between P2X7R and different
      enzymes involved in lipid metabolism represents a relatively new field in P2X7R
      research. This field of research began in epithelial cells and currently includes
      immune and nervous cells. The P2X7R-lipid metabolism pathway is related to many
      biological functions of P2X7R, such as cell death and pathogen clearance, and
      this signaling pathway may be involved in many functions that are dependent on
      bioactive lipids. In the present review, we will attempt to summarize data
      related to the P2X7R-lipid metabolism pathway, focusing on signaling pathways and
      their biological relevance to the immune system and infection.

PMID- 21845442
TI  - Can treating the diastolic blood pressure below a certain value increase
      cardiovascular risk?
AB  - The appearance of cardiovascular events when the diastolic blood pressure is
      lowered to some critical level is referred to as a "J-curve." Extensive data
      document the presence of a J-curve appearing when the diastolic blood pressure is
      lowered by antihypertensive medication to a level below 65 mm Hg, particularly in
      patients with underlying coronary heart disease even if such disease has not been
      clinically evident. Caution is needed in the more intensive and widespread
      treatment of hypertensive patients to avoid a J-curve.

PMID- 21845443
TI  - Can catheter-based renal denervation be used safely and effectively to
      substantially reduce blood pressure in treatment-resistant hypertensive patients?

PMID- 21845444
TI  - Expression and secretion of the human erythropoietin using an optimized cbh1
      promoter and the native CBH I signal sequence in the industrial fungus
      Trichoderma reesei.
AB  - The human erythropoietin (HuEPO) structural gene was fused with the secretion
      signal of the Trichoderma reesei cellobiohydrolase I and controlled by a newly
      optimized cbh1 promoter in an integrated expression vector pTrCBH-EPO. The
      recombinant HuEPO construct was transformed into two different T. reesei strains,
      a protease-deficient strain RutC-30 M3, and a glycosylation-modified strain T108.
      After lactose induction, the heterologous rHuEPO was found to be stably expressed
      in the selected transformants T47 (derived from RutC-30 M3) and T112 (derived
      from T108), which were shown to have high genetic stability. Secretion of
      erythropoietin in these transformants was further confirmed by SDS-PAGE and
      western blot analysis. Moreover, the secreted rHuEPO from T112 had an apparent
      molecular weight of 32 kDa, which was higher than from T47 (28 kDa) and similar
      to that of mammals (more than 30 kDa). These results demonstrate the potential of
      using industrial filamentous fungi for the production of human-derived
      erythropoietin.

PMID- 21845445
TI  - Fermentation of Korean red ginseng by Lactobacillus plantarum M-2 and its
      immunological activities.
AB  - We investigated ginsenoside transformation by fermentation of red ginseng with
      Lactobacillus plantarum M-2. We also examined the anti-metastasis and immune
      stimulating activities of EtOH extracts of fermented red ginseng (FRG-E) in
      animal and human subjects. Total sugar decreased from 85.5 mg mL(-1) to 44.1 mg
      mL(-1) with increasing culture time during the fermentation with L. plantarum M
      2. Uronic acid content reached a maximum level (534.3 MUg mL(-1)) at 3 days of
      fermentation and decreased thereafter. Ginsenoside metabolites increased from
      4,637.0 to 7,581.1 MUg mL(-1) after 4 days. The prophylactic intraperitoneal
      injection of FRG-E (500 MUg mouse(-1)) inhibited lung metastasis about 81.1%,
      while the inhibitory effect against tumor metastasis by treatment of EtOH extract
      from non-fermented red ginseng (NFRG-E) was 66.9%. Immunoglobulin A (IgA) and G
      (IgG) levels in the serum of healthy subjects were higher after FRG-E
      administration than at baseline, whereas NFRG-E induced reductions of these
      variables related to immunity. At 1 week, the change in IgA level by FRG-E (5.14
      mg mL(-1)) was significantly higher than that by NFRG-E (-14.50 mg mL(-1); p <
      0.05). It was concluded that the immunological activities of FRG-E were higher
      than those of NFRG-E, indicating that fermentation helped enhance the
      immunological activities of red ginseng.

PMID- 21845446
TI  - Assessing the viability of bacterial species in drinking water by combined
      cellular and molecular analyses.
AB  - The question which bacterial species are present in water and if they are viable
      is essential for drinking water safety but also of general relevance in aquatic
      ecology. To approach this question we combined propidium iodide/SYTO9 staining
      ("live/dead staining" indicating membrane integrity), fluorescence-activated cell
      sorting (FACS) and community fingerprinting for the analysis of a set of tap
      water samples. Live/dead staining revealed that about half of the bacteria in the
      tap water had intact membranes. Molecular analysis using 16S rRNA and 16S rRNA
      gene-based single-strand conformation polymorphism (SSCP) fingerprints and
      sequencing of drinking water bacteria before and after FACS sorting revealed: (1)
      the DNA- and RNA-based overall community structure differed substantially, (2)
      the community retrieved from RNA and DNA reflected different bacterial species,
      classified as 53 phylotypes (with only two common phylotypes), (3) the percentage
      of phylotypes with intact membranes or damaged cells were comparable for RNA- and
      DNA-based analyses, and (4) the retrieved species were primarily of aquatic
      origin. The pronounced difference between phylotypes obtained from DNA extracts
      (dominated by Betaproteobacteria, Bacteroidetes, and Actinobacteria) and from RNA
      extracts (dominated by Alpha-, Beta-, Gammaproteobacteria, Bacteroidetes, and
      Cyanobacteria) demonstrate the relevance of concomitant RNA and DNA analyses for
      drinking water studies. Unexpected was that a comparable fraction (about 21%) of
      phylotypes with membrane-injured cells was observed for DNA- and RNA-based
      analyses, contradicting the current understanding that RNA-based analyses
      represent the actively growing fraction of the bacterial community. Overall, we
      think that this combined approach provides an interesting tool for a concomitant
      phylogenetic and viability analysis of bacterial species of drinking water.

PMID- 21845447
TI  - Diagnosing ulnar neuropathy at the elbow using magnetic resonance neurography.
AB  - INTRODUCTION: Early diagnosis of ulnar neuropathy at the elbow is important.
      Magnetic resonance neurography (MRN) images peripheral nerves. We evaluated the
      usefulness of elbow MRN in diagnosing ulnar neuropathy at the elbow. METHODS: The
      MR neurograms of 21 patients with ulnar neuropathy were reviewed retrospectively.
      MRN was performed prospectively on 10 normal volunteers. The MR neurograms
      included axial T1 and axial T2 fat-saturated and/or axial STIR sequences. The
      sensitivity and specificity of MRN in detecting ulnar neuropathy were determined.
      RESULTS: The mean ulnar nerve size in the symptomatic and normal groups was 0.12
      and 0.06 cm(2) (P < 0.001). The mean relative signal intensity in the symptomatic
      and normal groups was 2.7 and 1.4 (P < 0.01). When using a size of 0.08 cm(2),
      sensitivity was 95% and specificity was 80%. DISCUSSION: Ulnar nerve size and
      signal intensity were greater in patients with ulnar neuropathy. MRN is a useful
      test in evaluating ulnar neuropathy at the elbow.

PMID- 21845449
TI  - [Karl Jaspers :  Tasks and limitations of psychotherapy].
AB  - Using Jaspers' methodically critical attitude (methodenkritische Einstellung) we
      distinguish three aspects of his understanding of psychotherapy: (1)
      psychotherapy gains scientific quality via methodical strictness (and is
      therefore independent of a therapist's weltanschauung); (2) psychotherapy is a
      (more or less) 'hermeneutical' method of self-enlightenment, offering limited
      statements with respect to one's life conduct; and (3) psychotherapy oversteps
      its epistemological limits if gaining the status of a weltanschauung, instead of
      leading to (existential) philosophizing in the face of transcendence. Following
      Jaspers we try to answer the question: What are the limits of psychotherapeutic
      methods with respect to questions of life conduct? The most important limit is
      the unbreakable linkage between the style of one's life conduct and the
      (personally) experienceable (superpersonal) sense of life, which cannot be
      disrupted with the means of any justifiable belief or falsifiable knowledge.
      Quite to the contrary, this existential linkage is the starting point of many
      psychotherapeutic interventions.

PMID- 21845448
TI  - HER2-based recombinant immunogen to target DCs through FcgammaRs for cancer
      immunotherapy.
AB  - Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long
      lasting antitumor effector cells aiming to control cancer progression. DC
      targeting is a critical step in the design of DC vaccines in order to optimize
      delivery and processing of the antigen, and several receptors have been
      characterized for this purpose. In this study, we employed the FcgammaRs to
      target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2
      Fc) composed of the immunogenic sequence of the human tumor-associated antigen
      HER2 (aa 364-391) and the Fc domain of a human IgG(1). In a mouse model, HER2-Fc
      cDNA vaccination activated significant T cell-mediated immune responses towards
      HER2 peptide epitopes as detected by IFN-gamma ELIspot and induced longer tumor
      latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies
      indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs
      through the FcgammaRs resulting in protein cross-processing and in the activation
      of autologous HER2-specific CD8(+) T cells from breast cancer patients.

PMID- 21845450
TI  - [Fingolimod treatment for multiple sclerosis patients. Infectiological aspects
      and recommendations for vaccinations].
AB  - Since April 2011 fingolimod (FTY 720, Gilenya(r)), a new oral treatment, is
      available for relapsing-remitting multiple sclerosis (MS) in Germany. Adverse
      effects in pre-marketing clinical controlled multicenter studies have led to
      specific precautions that have to be followed before initiating treatment.
      According to the European Union prescribing information fingolimod is not to be
      used as a first-line treatment, but is licensed as a second-line option or
      escalating therapy of MS. During treatment physical and neurological examinations
      as well as regular blood counts should be performed. The immunosuppressive mode
      of action of fingolimod requires increased awareness of infectious complications.
      Due to two fatal herpetic infections during the TRANSFORMS trial all patients
      without a history of chicken pox or without vaccination against varicella zoster
      virus (VZV) should be tested for antibodies to VZV. Comparably to other
      immunosuppressive treatment strategies the immune response to vaccines may be
      hampered during treatment with fingolimod. Thus, on the one hand, vaccination
      gaps should be closed before initiation of fingolimod treatment and, on the other
      hand, success of vaccinations during fingolimod therapy may have to be checked by
      antibody titre assessment.

PMID- 21845451
TI  - [Critical illness polyneuropathy und polymyopathy. How certain is the clinical
      diagnosis in patients with weaning failure?].
AB  - A frequent cause of weaning failure and the resultant long-term artificial
      ventilation is the generalized weakness syndrome in the sense of critical illness
      polyneuropathy or polymyopathy. However, hardly any information is presently
      available regarding the necessary intensity of the diagnostic workup for reaching
      or excluding a diagnosis with certainty in the neurological examination or
      regarding the additional diagnostic value of electrophysiological studies in
      patients receiving long-term acute care suspected of having critical illness
      polyneuropathy and polymyopathy. Therefore, the goal of this investigation was to
      address these questions. A total of 280 patients with complicated weaning were
      included in the study. All patients underwent clinical examination by a
      specialist in neurology and electrophysiological workup performed by another
      specialist. Among the patients studied, the greatest possible certainty of the
      diagnosis (positive predictive value) of the clinical examination was 97.9% [95%
      confidence interval (CI) 69.4-99.9] and the best certainty of excluding the
      diagnosis (negative predictive value) was 88.9% (95% CI 82.7-93.0). Thus, in
      difficult-to-wean patients who were considered to probably have the diagnosis of
      critical illness polyneuropathy or polymyopathy as assessed by a specialist,
      little additional information is gained from an electrophysiological study, which
      is hence dispensable in these cases.

PMID- 21845452
TI  - [Arthur Simons on tonic neck reflexes in persons with hemiplegia. From the years
      1916 to 1919].
AB  - Tonic neck reflexes described in 1921 by Magnus and deKlejn in animals and men
      were studied in hemiplegic patients who were mainly victims of WWI by Arthur
      Simons, a neurologist in Berlin and coworker of Hermann Oppenheim. The effect of
      the asymmetric neck reflexes after head rotation was restricted to the paralyzed
      side: tonus (spasms) of extension and adduction during mid-position of the head
      or head version to the paralyzed side; flexion tonus and abduction during head
      version to the non-paralyzed side; and flexion tonus (spasms) of the paralyzed
      limbs during flexion of the head and extension spasms by head extension. More
      than this, hemiplegic "Mitbewegungen" or associated reactions (Walshe) were
      observed. They are elicited by conscious innervations of the unaffected side,
      e.g. by fist closure, and are increased or varied by head rotation, the tonic
      neck reflexes. They occurred in 25%. A film with Arthur Simons as examiner from
      the years 1916-1919 shows these nearly forgotten phenomena. Their everyday
      significance was already stressed in 1920, long before the rules of antispastic
      positions were defined by Bobath.

PMID- 21845453
TI  - The seasonal and spatial patterns of ingestion of polyfilament nylon fragments by
      estuarine drums (Sciaenidae).
AB  - INTRODUCTION: Artisanal fisheries in tropical estuaries are an important economic
      activity worldwide. However, gear (e.g. ropes, nets, buoys, crates) and vessels
      are often in use under dangerous conditions. Polyfilament nylon ropes are used
      until they are well beyond human and environmental safety limits. Severe wear and
      tear results in the contamination of the environment with micro-fragments. The
      spread of these fragments in the marine environment and their ingestion by the
      biota are documented in the scientific literature and are increasing concerns.
      The aim of this study was to evaluate the ingestion of plastic fragments by two
      fish (drum) species in relation to seasonal, habitat and fish size-class
      variation. MATERIALS AND METHODS: The stomach contents of 569 individuals of
      Stellifer brasiliensis and Stellifer stellifer from the main channel of the
      Goiana Estuary were examined to identify variation in the number and the weight
      of plastic fragments and relate this variation to differences among the seasons
      (early dry, late dry, early rainy and late rainy), the habitats within the
      estuary (upper, middle and lower) and the size classes of the fish (juveniles,
      sub-adults and adults). RESULTS: Plastic fragments were found in 7.9% of the
      individuals of these two drum species captured from December 2005 to August 2008.
      Nylon fragments occurred in 9.2% of S. stellifer and 6.9% of S. brasiliensis
      stomachs. The highest number of nylon fragments ingested was observed in adults
      during the late rainy season in the middle estuary. DISCUSSION: Blue polyfilament
      nylon ropes are used extensively in fisheries and can be lost, inappropriately
      discarded or damaged during use in the estuary. These fragments were the only
      type of plastic detected during this study. The ingestion of nylon fragments by
      fish probably occurred during the animals' normal feeding activities. During the
      rainy season, the discharge of freshwater transports nylon fragments to the main
      channel and makes the fragments more available to fish. Fishery activities are
      responsible for a significant amount of the marine debris found in the estuary.
      CONCLUSIONS: The ingestion of fragments of nylon threads by fish is a
      demonstrated form of pollution in the Goiana Estuary. The physiological and
      toxicological consequences of the ingestion of this type of debris are unknown,
      as is the actual extent of the problem worldwide. The solutions to the problem
      are in the hands of authorities and communities alike because the good care and
      timely replacement of gear requires education, investment and effective policies.

PMID- 21845454
TI  - Cluster of symptoms in women with breast cancer treated with curative intent.
AB  - PURPOSE: The purpose of this study is to verify that there is a cluster of
      symptoms in women with breast cancer who were treated with curative intent and
      are free of disease. METHODS: One hundred and thirty-eight patients were
      recruited from the Mastology Department of Hospital A.C. Camargo with breast
      cancer, who have been treated with curative intent and concluded adjuvant
      chemotherapy 3-24 months prior who may or may not be using hormone therapy. The
      characterization of the sample was made through descriptive statistics (mean,
      standard deviation, median, and percentage). For evaluation of the cluster of
      symptoms, the following were used: Pearson correlation coefficient among the
      scales of Profile of Mood States, EORTC-QLQ-C30, and EORTC-BR23 and a factor
      analysis with principal components analysis with promax rotation (oblique). For
      the extraction of factors, an eigenvalue of 1 was considered, and to evaluate the
      permanence of symptom factor, a load greater than 0.40 was considered.
      Statistical significance was defined as p value <0.05. RESULTS: Through factor
      analysis of data, three distinct groupings were observed. Factor 1 corresponds to
      the psychoemotional symptoms and grouped as depression, confusion, anger,
      tension, fatigue, and breast symptoms. Factor 2 corresponds to physical symptoms,
      which include pain, dyspnea, arm symptoms, and insomnia. Finally, factor 3
      corresponds to gastrointestinal symptoms (inappetence, diarrhea, nausea, and
      vomiting). CONCLUSIONS: Through the data presented, the cluster of symptoms could
      be verified in women with breast cancer who were treated with curative intent and
      free of disease.

PMID- 21845455
TI  - Application of modified organo-nanoclay as the sorbent for zinc determination by
      FAAS: an optimization study of an online pre-concentration system.
AB  - An online column pre-concentration technique, coupled with flame atomic
      absorption spectrometry, was developed using a column filled with nanoclay
      modified with morin. For this purpose, zinc was determined in the water and
      biological samples. The sample solution was passed through the modified nanoclay
      column. The adsorbed zinc was subsequently eluted from the column with nitric
      acid solution. The optimization step was performed using two-level fractional
      factorial (2(5-2)) and Box-Behnken designs. Firstly, the fractional factorial
      design was performed for preliminary evaluation of the significant factors. The
      results showed that pH, amount of morin, and concentration of eluent were
      significant. The Box-Behnken experimental design was carried out in order to
      determine the optimum conditions. The optimum conditions were found to be at pH
      5.8, 1.8 mg L(-1) of morin and 3.0 mol L(-1) of eluent concentration. Under these
      optimum conditions, the limit of detection was found to be 0.11 MUg L(-1).
      Furthermore, the relative standard deviation of the ten replicate determinations
      was <2.8.0%. The method was validated by analyzing the zinc using a certified
      reference material that is NRCC-SLRS-4 riverine water. The developed procedure
      was applied to the extraction and determination of zinc in the water and
      biological samples.

PMID- 21845456
TI  - [Cancer-related fatigue and its psychosocial burden].
AB  - Cancer-related fatigue (CRF) is a highly prevalent and the most distressing
      symptom during and after treatment for cancer. It is characterized by feelings of
      physical and mental tiredness, weakness, and lack of energy and is not influenced
      by rest or sleep. Approximately 40% of patients suffer from CRF at diagnosis and
      nearly all patients experience fatigue during the course of cancer therapy. The
      impact of CRF on daily living and patient quality of life (QoL) is substantial.
      It profoundly affects patient quality of life and limits personal, social and
      occupational roles. The fatigue is also associated with significant levels of
      distress and it imposes a financial burden by limiting the ability to work. The
      underlying causes of CRF are poorly understood as are the relationship between
      fatigue and psychosocial distress, depression or anxiety. This paper seeks to
      give an overview of cancer-related fatigue and its psychosocial burden.

PMID- 21845457
TI  - Outcomes of severely injured adult trauma patients in an Australian health
      service: does trauma center level make a difference?
AB  - BACKGROUND: Trauma centers are designated to provide systematized
      multidisciplinary care to injured patients. Effective trauma systems reduce
      patient mortality by facilitating the treatment of injured patients at
      appropriately resourced hospitals. Several U.S. studies report reduced mortality
      among patients admitted directly to a level I trauma center compared with those
      admitted to hospitals with less resources. It has yet to be shown whether there
      is an outcome benefit associated with the "level of hospital" initially treating
      severely injured trauma patients in Australia. This study was designed to
      determine whether the level of trauma center providing treatment impacts
      mortality and/or hospital length of stay. METHODS: Outcomes were evaluated for
      severely injured trauma patients with an Injury Severity Score (ISS) > 15 using
      NSW Institute of Trauma and Injury Management data from 2002-2007 for our
      regional health service. To assess the association between trauma centers and
      binary outcomes, a logistic regression model was used. To assess the association
      between trauma centers and continuous outcomes, a multivariable linear regression
      model was used. Sex, age, and ISS were included as covariates in all models.
      RESULTS: There were 1,986 trauma presentations during the 6-year period. Patients
      presenting to a level III trauma center had a significantly higher risk of death
      than those presenting to the level I center, regardless of age, sex, ISS, or
      prehospital time. Peer review of deaths at the level III center identified
      problems in care delivery in 15 cases associated with technical errors, delay in
      decision making, or errors of judgement. CONCLUSION: Severely injured patients
      treated at a level III center had a higher mortality rate than those treated at a
      level I center. Most problems identified occurred in the emergency department and
      were related to delays in care provision. This research highlights the importance
      of efficient prehospital, in-hospital, and regional trauma systems, performance
      monitoring, peer review, and adherence to protocols and guidelines.

PMID- 21845458
TI  - Outcome after open repair of ruptured abdominal aortic aneurysm in patients >80
      years old: a systematic review and meta-analysis.

PMID- 21845460
TI  - Helix pomatia agglutinin binding glycoproteins in thyroid tumors.
AB  - BACKGROUND: Binding of the lectin Helix pomatia agglutinin (HPA) has been shown
      to be associated with poor prognosis in many human cancers, but not in thyroid
      cancer. The aims of the present study were to assess alteration in cellular
      glycosylation, detected by HPA binding, in thyroid tumors; to determine if such
      altered glycosylation carries any prognostic significance; and to analyze
      qualitative and quantitative differences of HPA-binding glycoproteins in various
      thyroid tumors. METHODS: Lectin histochemistry was performed on 110 archival
      paraffin wax embedded specimens of various thyroid tumors excised between the
      years 1983-1993. Demographic data, histological data, and time to death were
      recorded, and multivariate Cox regression analysis was performed to determine a
      prognostic model for patient survival based on the data. Helix pomatia agglutinin
      binding glycoproteins were isolated from 128 fresh specimens of various thyroid
      tissues by affinity chromatography, analyzed by SDS-PAGE and western blotting.
      RESULTS: There was a marked qualitative difference in the profile of HPA-binding
      glycoproteins, with the malignant thyroid tumors showing a heterogeneous profile
      of numerous HPA binding glycoprotein bands. Lectin histochemistry showed
      significant positive HPA binding in malignant thyroid tumors (p = 0.0009). Kaplan
      Meir survival analysis revealed that among patients who died of their disease
      those with HPA-positive tumors had a significantly shorter survival (p = 0.009).
      CONCLUSIONS: This is the first study showing that HPA binding glycoproteins are
      synthesized by thyroid tumors. Thyroid cancers show a broader profile of HPA
      binding glycoproteins compared to benign thyroid tumors, and positive HPA binding
      is significantly associated with shorter survival and poorer prognosis in thyroid
      cancers.

PMID- 21845461
TI  - Indications, imaging technique, and reading of cardiac computed tomography:
      survey of clinical practice.
AB  - OBJECTIVES: To obtain an overview of the current clinical practice of cardiac
      computed tomography (CT). METHODS: A 32-item questionnaire was mailed to a total
      of 750 providers of cardiac CT in 57 countries. RESULTS: A total of 169
      questionnaires from 38 countries were available for analysis (23%). Most CT
      systems used (94%, 207/221) were of the latest generation (64-row or dual-source
      CT). The most common indications for cardiac CT was exclusion of coronary artery
      disease (97%, 164/169). Most centres used beta blockade (91%, 151/166) and
      sublingual nitroglycerine (80%, 134/168). A median slice thickness of 0.625 mm
      with a 0.5-mm increment and an 18-cm reconstruction field of view was used.
      Interpretation was most often done using source images in orthogonal planes (92%,
      155/169). Ninety percent of sites routinely evaluate extracardiac structures on a
      large (70%) or cardiac field of view (20%). Radiology sites were significantly
      more interested in jointly performing cardiac CT together with cardiology than
      cardiologists. The mean examination time was 18.6 +/- 8.4 min, and reading took
      on average 28.7 +/- 17.8 min. CONCLUSIONS: Cardiac CT has rapidly become
      established in clinical practice, and there is emerging consensus regarding
      indications, conduct of the acquisition, and reading.

PMID- 21845462
TI  - Comparison of diffusion-weighted MR imaging and FDG PET/CT to predict
      pathological complete response to neoadjuvant chemotherapy in patients with
      breast cancer.
AB  - OBJECTIVE: To compare the use of diffusion-weighted MR imaging (DWI) and (18)F
      FDG PET/CT to predict pathological complete response (pCR) in breast cancer
      patients receiving neoadjuvant chemotherapy. METHODS: Thirty-four women with 34
      invasive breast cancers underwent DWI and PET/CT before and after chemotherapy
      and before surgery. The percentage changes in the apparent diffusion coefficient
      (ADC) and the standardised uptake value (SUV) were calculated, and the diagnostic
      performances for predicting pCR were evaluated using receiver operating
      characteristic (ROC) curve analysis. RESULTS: After surgery, 7/34 patients
      (20.6%) were found to have pCR. A( z ) values for DWI, PET/CT and the combined
      use of DWI and PET/CT were 0.910, 0.873 and 0.944, respectively. The best cut
      offs for differentiating pCR from non-pCR were a 54.9% increase in the ADC and a
      63.9% decrease in the SUV. DWI showed 100% (7/7) sensitivity and 70.4% (19/27)
      specificity and PET/CT showed 100% sensitivity and 77.8% (21/27) specificity.
      When DWI and PET/CT were combined, there was a trend towards improved specificity
      compared with DWI. CONCLUSIONS: DWI and FDG PET/CT show similar diagnostic
      accuracy for predicting pCR to neoadjuvant chemotherapy in breast cancer
      patients. The combined use of DWI and FDG PET/CT has the potential to improve
      specificity in predicting pCR.

PMID- 21845463
TI  - Dual source multidetector CT-angiography before Transcatheter Aortic Valve
      Implantation (TAVI) using a high-pitch spiral acquisition mode.
AB  - OBJECTIVES: Transcatheter Aortic Valve Implantation (TAVI) is an alternative to
      surgical valve replacement in high risk patients. Angiography of the aortic root,
      aorta and iliac arteries is required to select suitable candidates, but contrast
      agents can be harmful due to impaired renal function. We evaluated ECG-triggered
      high-pitch spiral dual source Computed Tomography (CT) with minimized volume of
      contrast agent to assess aortic root anatomy and vascular access. METHODS: 42
      patients (82 +/- 6 years) scheduled for TAVI underwent dual source (DS) CT
      angiography (CTA) of the aorta using a prospectively ECG-triggered high-pitch
      spiral mode (pitch = 3.4) with 40 mL iodinated contrast agent. We analyzed aortic
      root/iliac dimensions, attenuation, contrast to noise ratio (CNR), image noise
      and radiation exposure. RESULTS: Aortic root/iliac dimensions and distance of
      coronary ostia from the annulus could be determined in all cases. Mean aortic and
      iliac artery attenuation was 320 +/- 70 HU and 340 +/- 77 HU. Aortic/iliac CNR
      was 21.7 +/- 6.8 HU and 14.5 +/- 5.4 HU using 100 kV (18.8 +/- 4.1 HU and 8.7 +/-
      2.6 HU using 120 kV). Mean effective dose was 4.5 +/- 1.2 mSv. CONCLUSIONS: High
      pitch spiral DSCTA can be used to assess the entire aorta and iliac arteries in
      TAVI candidates with a low volume of contrast agent while preserving diagnostic
      image quality.

PMID- 21845464
TI  - Detection of intrarenal microstructural changes with supersonic shear wave
      elastography in rats.
AB  - OBJECTIVES: To evaluate, in a rat model of glomerulosclerosis, whether ultrasonic
      shear wave elastography detects kidney cortex stiffness changes and predicts
      histopathological development of fibrosis. MATERIALS AND METHODS: Three groups
      were studied transversally: a control group (n = 8), a group after 4 weeks of L
      NAME administration (H4, n = 8), and a group after 6 weeks (H6, n = 15). A fourth
      group was studied longitudinally (n = 8) before, after 4 weeks and after 7 weeks
      of L-NAME administration. Shear modulus of renal cortex was quantified using
      supersonic shear imaging technique. Urine was analysed for dosage of
      protein/creatinine ratio. Kidneys were removed for histological quantification of
      fibrosis. RESULTS: Diseased rats showed an increased urinary protein/creatinine
      ratio. Cortical stiffness expressed as median (interquartile range) was 4.0 kPa
      (3.3-4.5) in control kidneys. It increased in all but one pathological groups:
      H4: 7.7 kPa (5.5-8.6) (p < 0.01); H6: 4.8 kPa (3.9-5.9) (not significant); in the
      longitudinal cohort, from 4.5 kPa (3.1-5.9) to 7.7 kPa (5.9-8.3) at week 4 (p <
      0.05) and to 6.9 kPa (6.1-7.8) at week 7 (p < 0.05). Stiffness values were
      correlated with the proteinuria/creatininuria ratio (r = 0.639, p < 0.001).
      CONCLUSIONS: Increased cortical stiffness is correlated with the degree of renal
      dysfunction. More experience in other models is necessary to understand its
      relationship with microstructural changes.

PMID- 21845465
TI  - Invasive warm-season grasses reduce mycorrhizal root colonization and biomass
      production of native prairie grasses.
AB  - Soil organisms play important roles in regulating ecosystem-level processes and
      the association of arbuscular mycorrhizal (AM) fungi with a plant species can be
      a central force shaping plant species' ecology. Understanding how mycorrhizal
      associations are affected by plant invasions may be a critical aspect of the
      conservation and restoration of native ecosystems. We examined the competitive
      ability of old world bluestem, a non-native grass (Caucasian bluestem
      [Bothriochloa bladhii]), and the influence of B. bladhii competition on AM root
      colonization of native warm-season prairie grasses (Andropogon gerardii or
      Schizachyrium scoparium), using a substitutive design greenhouse competition
      experiment. Competition by the non-native resulted in significantly reduced
      biomass production and AM colonization of the native grasses. To assess plant
      soil feedbacks of B. bladhii and Bothriochloa ischaemum, we conducted a second
      greenhouse study which examined soil alterations indirectly by assessing biomass
      production and AM colonization of native warm-season grasses planted into soil
      collected beneath Bothriochloa spp. This study was conducted using soil from four
      replicate prairie sites throughout Kansas and Oklahoma, USA. Our results indicate
      that a major mechanism in plant growth suppression following invasion by
      Bothriochloa spp. is the alteration in soil microbial communities. Plant growth
      was tightly correlated with AM root colonization demonstrating that mycorrhizae
      play an important role in the invasion of these systems by Bothriochloa spp. and
      indicating that the restoration of native AM fungal communities may be a
      fundamental consideration for the successful establishment of native grasses into
      invaded sites.

PMID- 21845466
TI  - The influence of patellar position on soft tissue balance in minimal incision
      total knee arthroplasty.
AB  - PURPOSE: This study aims to clarify the influence of surgical exposure on intra
      operative soft tissue balance measurements using a new tensor in minimal incision
      total knee arthroplasty (TKA). METHODS: Sixty patients with osteoarthritis of the
      knee received minimal incision TKAs. Twenty patients received a posterior
      stabilized TKA using a quadriceps sparing approach, and the other forty patients,
      using a limited medial parapatellar (mini) approach. After femoral trial
      placement, soft tissue balance was measured using an offset type tensor at full
      extension and 90 degrees  of knee flexion, with the patella both laterally
      retracted and reduced. The joint component gap and varus imbalance were used to
      assess the difference in patellar position and surgical exposure. RESULTS: At
      extension, the joint component gap and varus imbalance showed no statistical
      difference regardless of patellar position in either TKA. However, the joint
      component gaps decreased at 90 degrees  of flexion when the patella was laterally
      retracted in both TKAs. Additionally, a significantly smaller joint gap was
      observed in the quadriceps sparing TKA than the mini-TKA with a retracted patella
      at 90 degrees  of flexion. Varus ligament imbalances decreased with the patella
      laterally retracted at 90 degrees  of flexion in the quadriceps sparing TKA, not
      in the mini-TKA. CONCLUSION: Surgeons should be aware of the influence in
      surgical exposure of the joint gap and ligament balance during patella shift in
      minimal incision TKA. LEVEL OF EVIDENCE: III.

PMID- 21845467
TI  - Computer-assisted mosaic arthroplasty using patient-specific instrument guides.
AB  - PURPOSE: Success of mosaic arthroplasty requires that the transplanted plugs be
      positioned to reconstruct the curvature and height of the original articular
      surface. This case report demonstrates how to achieve correct plug positioning
      using patient-specific instrument guides manufactured on a 3D printer. METHODS:
      Using a 3D computer model of bone and cartilage, the harvesting of plugs and
      their placement at the defect site was planned on the computer. Instrument guides
      were manufactured in thermoplastic on a 3D printer; the bottom surface of the
      guides fit to the contour of the knee and the top surface contained holes to
      precisely position the surgical instruments. The instrument guides were used on a
      young female patient to repair a large articular cartilage defect in the left
      knee. RESULTS: The patient showed an increased range of motion in the knee and
      also a decrease in pain and discomfort at her 2-year follow-up. A CT arthrogram
      at 2 years postoperative showed a smooth and appropriate contour of the
      reconstructed cartilage over the defect. CONCLUSIONS: Image-based preoperative
      planning and the use of patient-specific instrument guides can yield a good
      patient outcome without requiring optically tracked intraoperative guidance.

PMID- 21845468
TI  - The role of chronic kidney disease as a predictor of outcome after
      revascularisation of the ulcerated diabetic foot.
AB  - AIMS/HYPOTHESIS: The aim of the study was to stratify the risk of diabetic
      patients with leg ulcer or gangrene undergoing infrainguinal revascularisation
      for critical limb ischaemia. METHODS: The study cohort included 732
      revascularisation procedures performed in 597 diabetic patients with ulcer or
      gangrene. Logistic regression and CART analysis were used for identification of
      predictors of 1-year outcome. RESULTS: Logistic regression showed that chronic
      kidney disease (CKD) class (OR 1.38, 95% CI 1.16, 1.65) was an independent
      predictor of 1-year leg salvage (area under the receiver operating characteristic
      [ROC] curve 0.60, 95% CI 0.54, 0.65). The terminal nodes of the CART for 1-year
      leg salvage were CKD classes 4-5, the level (infrapopliteal vs femoropopliteal
      revascularisation), type of revascularisation (bypass surgery vs percutaneous
      transluminal angioplasty) and gangrene (area under the ROC curve 0.62, 95% CI
      0.57, 0.68). Logistic regression showed that pulmonary disease (OR 1.76, 95% CI
      1.11, 2.78), CKD class (OR 1.43, 95% CI 1.24, 1.65), foot gangrene (OR 1.76, 95%
      CI 1.21, 2.60) and patient age (OR 1.02, 95% CI 1.01, 1.04) were independent
      predictors of 1-year amputation-free survival (area under the ROC curve 0.65, 95%
      CI 0.60, 0.69). The terminal nodes of the CART for 1-year amputation-free
      survival were CKD classes 3-5, patient's age of >= 75 years and foot gangrene
      (area under the ROC curve 0.64, 95% CI 0.60, 0.68). CONCLUSIONS/INTERPRETATION:
      CKD is a formidable risk factor for poor intermediate outcome after infrainguinal
      revascularisation in diabetic patients with foot ulcer or gangrene. CART analysis
      indicates that foot gangrene is also a significant risk factor for adverse
      outcome.

PMID- 21845469
TI  - Taking care of the challenging tension headache patient.
AB  - Tension type headache (TTH) is the most common primary headache disorder, but it
      is a diagnosis for which patients infrequently present for evaluation in the
      outpatient setting. Performing a thorough evaluation and establishing the correct
      diagnosis is essential in formulating an effective treatment plan. There are many
      complex issues that, although not causative, may play an exacerbating role in
      TTH. This article reviews the epidemiology, diagnosis, and pharmacologic
      treatment of TTH. In addition, nonpharmacologic treatment approaches, sleep
      dysfunction, and temporomandibular dysfunction are reviewed.

PMID- 21845470
TI  - Prospective audit and feedback on antibiotic prescription in an adult hematology
      oncology unit in Singapore.
AB  - We evaluated the impact of a prospective audit and feedback antimicrobial
      stewardship program (ASP) on antibiotic prescription and resistance trends in a
      hematology-oncology unit in a university hospital (National University Cancer
      Institute, Singapore [NCIS]). A prospective interrupted time-series study
      comprising 11-month pre-intervention (PIP) and intervention evaluation phases
      (IEP) flanking a one-month implementation phase was carried out. Outcome measures
      included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and
      all antibiotics (encompassing audited and non-audited antibiotics), and the
      incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal
      and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and
      DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital.
      There were 580 ASP recommendations from 1,276 audits, with a mean monthly
      compliance of 86.9%. Significant reversal of prescription trends towards reduced
      prescription of audited (coefficient = -2.621; 95% confidence interval [CI]: 
      4.923, -0.319; p = 0.026) and all evaluated antibiotics (coefficient = -4.069;
      95% CI: -8.075, -0.063; p = 0.046) was observed. No changes were seen for both
      internal and external controls, except for the reversal of prescription trends
      for cephalosporins hospital-wide. Antimicrobial resistance did not change over
      the time period of the study. Adverse outcomes-the majority unavoidable-occurred
      following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be
      implemented in the complex setting of hematology-oncology inpatients.

PMID- 21845471
TI  - Triple inhibitory activity of Cliona celata against TNF-alpha-induced matrix
      metalloproteinase-9 production via downregulated NF-kappaB and AP-1, enzyme
      activity, and migration potential.
AB  - Extracellular matrix-degrading protease, matrix metalloproteinase-9 (MMP-9), is
      known to be involved in vascular smooth muscle cell (SMC)'s aberrant
      proliferation and movement in atherosclerotic lesions. During screening of the
      MMP-9-inhibitory compounds from marine animal resources, we have found that the
      ethyl acetate extract from Cliona celata (ECC) effectively inhibits the SMC
      derived MMP-9 enzyme activity and gene expression. In addition, the ECC
      effectively repressed the migration potential of the tumor necrosis factor-alpha
      (TNF-alpha)-stimulated human aortic smooth muscle cell (HASMC). As assessed by
      Western blot analysis, the produced MMP-9 protein levels in the TNF-alpha-induced
      HASMC were significantly decreased by the concomitant treatment of ECC at the 50-
      to 300-MUg/mL concentration ranges. In addition, in the RT-PCR experiment, the
      expressed MMP-9 mRNA levels in the TNF-alpha-induced HASMC were seemingly
      decreased by ECC treatment at the same concentration ranges (50-300 MUg/mL). For
      the action mechanism(s) of ECC to the phenotype changes in HASMC, we have further
      evaluated the ECC's pharmacological activities on the signal molecules which are
      importantly linked in the MMP-9 expression and cell migration potential of HASMC.
      We have found that extracellular signal-regulated kinase 1 and 2 (ERK1/2)
      phosphorylation as a target point is suppressed by the ECC treatment in the TNF
      alpha-treated HASMC. Using electrophoretic mobility shift assay, the nuclear
      extracts purified from ECC-treated HASMCs were shown to decrease the binding
      potentials on the labeled nuclear factor-kappaB (NF-kappaB) and activator protein
      1 probes. NF-kappaB p65 and phosphorylated c-Jun contents were also decreased in
      the purified nuclear extracts from the ECC-treated HASMC, as confirmed by Western
      blot analysis. Finally, it was shown that the ECC-treated HASMCs were less
      migrated when compared to the TNF-alpha-treated cells, as confirmed by HASMC
      migration assays using the 8-MUm pore transwell membranes. From these results, it
      was proposed that ECC has a potentially applicable anti-atherosclerotic activity.

PMID- 21845472
TI  - Comparing efficacy of alpha1D-receptor antagonist naftopidil and alpha1A/D
      receptor antagonist tamsulosin in management of distal ureteral stones.
AB  - PURPOSE: To compare the efficacy of alpha(1)D-receptor antagonist Naftopidil and
      alpha(1)A/D-receptor antagonist Tamsulosin in management of distal ureteral
      stones. MATERIALS AND METHODS: A total of 131 patients with distal ureteral
      stones were included in the study from December 2008 to September 2010. The
      patients were randomized to 3 groups: group 1 (43 patients), those receiving 10
      mg naftopidil once daily; group 2 (45 patients), those receiving 0.4 mg
      tamsulosin once daily; and group 3 (43 patients) were given a watchful waiting
      and served as control group. All patients were followed up for 2 weeks.
      Ultrasonography and kidney-ureters-bladder (KUB) were performed on day 7 and 14.
      At the end of the follow-up period, patients who failed to expel the stone were
      scheduled to undergo ESWL or ureteroscopy. RESULTS: Stone expulsion was observed
      in 31 patients in group 1 (72.1%), 37 patients in group 2 (82.2%), and 13
      patients in group 3 (30.2%). A statistically significant difference was noted
      with Chi-square testing between groups 1 and 3, and groups 2 and 3 (P = 0.000 and
      P = 0.000, respectively). Average time to expulsion was 7.6 +/- 2.26 days (range
      1-12 days) in group 1, 7.7 +/- 1.94 days (range 2-11 days) in group 2, and 9.4 +/
      2.48 days (range 6-14 days) in group 3. A statistically significant difference
      was observed in time to expulsion between groups 1 and 3, and groups 2 and 3 (P =
      0.000, P = 0.001, respectively) by ANOVA testing. The side effects encountered in
      the study groups were generally mild and did not require cessation of therapy in
      any patient. CONCLUSIONS: Naftopidil could significantly increase spontaneous
      passage of distal ureteral stones with low side effects. The stone expulsion rate
      is similar for the tamsulosin.

PMID- 21845473
TI  - Psychoactive substance use and the risk of motor vehicle crash injuries in
      southern Taiwan.
AB  - The purpose of this study was to examine the association between psychoactive
      drug use and motor vehicle crash (MVC) injuries requiring hospitalization in
      southern Taiwan. A case-control study was conducted in southern Taiwan from
      January 2009 to December 2009. The cases included car or van drivers who were
      involved in MVCs and required hospitalization. Demographic and trauma-related
      data were collected from questionnaires and hospital and ambulance records. Urine
      and/or blood samples were collected on admission. The controls consisted of
      drivers who were randomly recruited while driving on public roads. Study subjects
      were interviewed and asked to provide urine samples. All blood and urine samples
      were tested for alcohol and a number of other legal and illegal drugs. Only those
      subjects who provided urine and/or blood specimens were included in the study.
      During the study period, 254 case patients and 254 control drivers were enrolled.
      The analysis showed an odds ratio (OR) of 3.41 (95% confidence intervals (95%
      CI), 1.76-6.70; p < 0.001) for persons taking benzodiazepines, and an OR of 3.50
      (95% CI, 1.81-6.85; p < 0.001) for those taking alcohol (blood alcohol
      concentrations (BAC) >= 0.8 g/l) with regard to hospitalizations due to MVCs. For
      persons taking combinations of benzodiazepines and alcohol, the OR increased to
      5.12 (95% CI: 1.77-15.91, p < 0.001). This study concluded that drug use among
      motor vehicle drivers increases the risk of MVCs that require hospitalization.
      From a public health perspective, the high risk ratios are concerning, and
      preventive measures are warranted.

PMID- 21845474
TI  - The roles of P2X7 receptor in regional-specific microglial responses in the rat
      brain following status epilepticus.
AB  - Recently, we have reported that astroglial activations in response to status
      epilepticus (SE) show regional-specific manners in the rat hippocampus. However,
      it is unknown that microglial responses to SE would show regional-specific
      patterns. Therefore, the present study was designed to elucidate the regional
      specific microglial activation and relationship between P2X7 receptor functions
      and SE-induced microglial responses in the rat brain. Following SE, microglia
      appeared amoeboid or phagocytic in the dentate gyrus and the piriform cortex. In
      contrast, elongated microglia were observed in the CA1 hippocampal regions and
      the frontoparietal cortex. In the dentate gyrus, the CA1 hippocampal regions, and
      the frontoparietal cortex, these microglial activation accelerated by BzATP (a
      P2X7 receptor agonist)-infusion, but inhibited by OxATP (a P2X7 receptor
      antagonist). However, SE-induced microglial activation in the piriform cortex was
      not affected by BzATP or OxATP-infusion. Therefore, our findings indicate that SE
      induced microglial activation may show regional-specific manners, and suggest
      that P2X7 receptor function differently modulates SE-induced microglial responses
      in distinct brain regions.

PMID- 21845475
TI  - A possible synaptic configuration underlying coeruleospinal inhibition of
      visceral nociceptive transmission in the rat.
AB  - A synaptic arrangement underlying descending inhibition from the locus
      coeruleus/subcoeruleus (LC/SC) on visceral nociceptive transmission in the spinal
      cord was investigated in the anesthetized rat. Extracellular recordings were made
      from the L(6)-S(2) segmental level using a carbon filament glass microelectrode
      (4-6 MOmega). Colorectal distention (CRD) was produced by inflating a balloon
      inside the descending colon and rectum. All neurons tested responded to both CRD
      and to cutaneous pinch (a force of 613 g/mm(2)), indicating that nociceptive
      signals from visceral organs and nociceptive signals from the cutaneous receptive
      field converge on a single neuron. These neurons were divided into two groups
      based on their response to CRD: short latency-abrupt and short latency-sustained
      neurons. Electrical stimulation of the LC/SC (30 or 50 MUA, 100 Hz, 0.1 ms
      pulses) inhibited both CRD-evoked and cutaneous pinch-evoked responses in short
      latency-abrupt and short latency-sustained neurons. When graded CRD (20, 40, 60,
      and 80 mmHg) was delivered, LC/SC stimulation produced a reduction in slope of
      the linear CRD intensity-response magnitude curve without a change in the
      response threshold in both short latency-abrupt (n = 42) and short latency
      sustained neurons (n = 11). This result suggests that coeruleospinal inhibition
      of visceral nociceptive transmission is due to a synaptic configuration in which
      inhibitory and excitatory terminals are in close spatial proximity, including
      presynaptic inhibition.

PMID- 21845477
TI  - Letter from the editors-in-chief.

PMID- 21845476
TI  - The magnetic resonance spectroscopy findings of extrapontine myelinolysis in a
      patient with acute lymphoblastic leukemia.
AB  - The magnetic resonance (MR) spectroscopy findings of extrapontine myelinolysis
      have been rarely reported. Herein, we present MR spectroscopy findings as well as
      the conventional MR and diffusion MR findings of an acute lymphoblastic leukemia
      patient with extrapontine myelinolysis. Advanced MR imaging including diffusion
      weighted imaging and MR spectroscopy may be helpful to exclude other pathologies
      in the differential diagnosis and make the diagnosis when there is a diagnostic
      difficulty on cases clinically suspicious for extrapontine myelinolysis.

PMID- 21845478
TI  - [Reality of provision of care in Germany in the fields of orthopedics and
      casualty surgery].

PMID- 21845479
TI  - A clinical commentary on the article "biomaterials advances in patches for
      congenital heart defect repair" : cardiac bioengineering for congenital heart
      disease: time for progress.

PMID- 21845480
TI  - A new technique for sphincter-preserving anal fistula repair using a novel radial
      emitting laser probe.
AB  - Anal fistula repair still remains challenging. Up to 30% of fistulas persist
      after surgery despite many improvements in surgical skills and technique. One
      major reason for surgical failure is a persistent fistula track or remnants of
      the fistula epithelium which could not be removed during surgery. To overcome
      this problem, a novel technique was developed using a newly invented radial
      emitting laser probe ("FiLaCTM", Biolitec, Germany) to destroy the fistula
      epithelium and to simultaneously obliterate the remaining fistula track. In a
      pilot study, we operated on 11 patients with cryptoglandular anal fistula. All
      patients underwent previous surgery up to 6 times prior to definitive surgery. In
      the primary operation, the initial abscess was drained, the internal opening of
      the fistula identified and seton drainage placed. During fistula repair, we used
      the flap technique for conventional closure of the internal opening. The
      remaining fistula track was cleaned mechanically, the laser inserted into the
      track and energy applied homogeneously at a wavelength of 1,470 nm and 13 watt.
      While providing continuous retraction of the probe, the remaining epithelium was
      destroyed and the fistula track obliterated. The median follow-up was 7.4 months.
      Nine out of 11 fistulas showed primary healing (81.8%). Only one minor form of
      incontinence (limited soiling) was observed and no complications occurred. The
      use of a novel diode laser source and a radial emitting laser probe in addition
      to conventional surgery is a very promising new technique in sphincter-preserving
      anal fistula repair. The observed healing rate is high. Due to minimized trauma
      to the sphincter muscle, there are good short-term functional results without
      observable procedure-related complications.

PMID- 21845481
TI  - [Therapy-resistant aggressive cystic lesion of the mandible].
AB  - Several extensive surgical interventions of a cystic lesion in the left mandible
      were followed by recurrences. The lesion extended from the primary mandibular
      region into the area of pterygopalatine fossa finally infiltrating the orbital
      region and the skull base. Histological results could never demonstrate a
      malignancy with certainty. Due to the patient's poor general condition, the
      refusal for further surgical inventions and due to the malignoma-like growth
      pattern radiation treatment was performed. However, this had no effect on tumor
      progression.

PMID- 21845482
TI  - [(No) Fear of audits? Control is good, trust is better. Audits as a core element
      of quality management].
AB  - Quality management (QM) cannot be successfully implemented and performed without
      audits. The PDCA (Plan-Do-Check-Act) cycle is the core component of QM systems.
      In this cycle an audit represents the crucial step "check". Audits verify whether
      the performed actions and their results conform to the requirements. It is
      especially important to verify whether the principles of QM are omnipresent and
      fully implemented in a department or institution. The announcement of an audit
      may cause mixed feelings or even anxiety among the personnel to be audited.
      Without previous information and training the audit may be perceived as an act of
      control and intrusion into departmental affairs. The colleagues often fear
      sanctions if lapses are found or consider the audit to be a cross-examination.
      However, an audit is rather meant to be a helpful aid and a chance to
      continuously improve the departmental QM system by means of a constructive
      communication among colleagues. In the year 2009 the European Commission
      published guidelines for the performance of clinical audits in medical radiology,
      including diagnostic radiology, nuclear medicine and radiation therapy (Council
      Directive 97 / 43 / EURATOM). The aim is an optimal protection of the individual
      from the hazards of ionizing radiation and the directive expects radiological
      departments to perform clinical audits in accordance with national procedures.

PMID- 21845483
TI  - [Laparoscopic anterior versus posterior fundoplication : new evidence level from
      meta-analysis].

PMID- 21845485
TI  - Paramedian thoracic epidural training model.

PMID- 21845484
TI  - [Microsurgical techniques for breast reconstruction].
AB  - The results of a survey show that less then 10% of affected women are aware of
      the various options for breast reconstruction. However, in modern medicine the
      correlation between emotional well-being and physical health has been established
      as an important factor. The first successful autologous breast reconstruction was
      performed by Czerny in 1895. After introduction of silicon implants for breast
      augmentation this method was also increasingly used for breast reconstruction.
      Worldwide most reconstructions are implant based, however the symptomatic rate of
      capsular contracture is up to 38% and the reoperation rate for implant-based
      reconstruction and radiotherapy up to 35%. Autologous reconstruction procedures
      have a significantly lower complication rate. This article describes the modern
      microsurgical techniques for breast reconstruction and discusses the indications
      and achievable results.

PMID- 21845486
TI  - Harmonization of regulatory approaches for evaluating therapeutic equivalence and
      interchangeability of multisource drug products: workshop summary report.
AB  - Regulatory approaches for evaluating therapeutic equivalence of multisource (or
      generic) drug products vary among different countries and/or regions.
      Harmonization of these approaches may decrease the number of in vivo
      bioequivalence studies and avoid unnecessary drug exposure to humans. Global
      harmonization for regulatory requirements may be promoted by a better
      understanding of factors underlying product performance and expectations from
      different regulatory authorities. This workshop provided an opportunity for
      pharmaceutical scientists from academia, industry and regulatory agencies to have
      open discussions on current regulatory issues and industry practices,
      facilitating harmonization of regulatory approaches for establishing therapeutic
      equivalence and interchangeability of multisource drug products.

PMID- 21845487
TI  - Use of a pharmaceutically adulterated dietary supplement, Pai You Guo, among
      Brazilian-born women in the United States.
AB  - BACKGROUND: Pai You Guo is a weight loss supplement manufactured in China and
      adulterated with the banned pharmaceutical products sibutramine and
      phenolphthalein. The US Food and Drug Administration (FDA) announced a voluntary
      recall of Pai You Guo in 2009, yet clinicians have noted its continued use among
      Brazilian-born women in Massachusetts. OBJECTIVE: To assess prevalence of Pai You
      Guo use, associated side effects, modes of acquisition, and impact of FDA
      regulatory action on these outcomes. DESIGN: Cross-sectional study using an
      anonymous questionnaire. PARTICIPANTS: Women <=60 years of age, born in Brazil
      who attended one primary care clinic or one of six churches in Massachusetts.
      MAIN MEASURES: Prevalence of use, how users first heard about the product,
      location of purchase, associated side effects, patterns of use before and after
      the FDA recall. KEY RESULTS: Twenty-three percent (130/565) of respondents
      reported using Pai You Guo. In multivariate analysis, obesity (adj OR 3.7, p
      value <0.001) and lack of insurance (adj OR 2.6, p-value 0.005) were associated
      with use. The majority of users (85%) reported at least one side effect. Dry
      mouth (59%), anxiety (29%), and insomnia (26%) were most commonly reported
      adverse effects. Nearly thirty-percent of users (38/130) purchased Pai You Guo
      from local stores and 9% (11/130) purchased it over the Internet. The majority of
      respondents (79/130; 61%) purchased Pai You Guo after the FDA recall. No
      respondent was aware of the FDA recall. CONCLUSIONS: Use of this pharmaceutically
      adulterated supplement is common among Brazilian-born women in Massachusetts. The
      FDA alerts and recall did not appear to decrease its use.

PMID- 21845488
TI  - Assessing balance and mobility to track illness and recovery in older inpatients.
AB  - BACKGROUND: Archetypal symptoms and signs are commonly absent in frail older
      people who are acutely unwell. This challenges both recognition of illness and
      monitoring of disease progression in people at high risk of prolonged hospital
      stays, institutionalization and death. OBJECTIVE: To determine whether bedside
      assessment of balance and mobility could track acute changes in the health status
      of older people admitted to hospital. DESIGN: Prospective cohort study.
      PARTICIPANTS: Four hundred nine patients, with a mean age of 81.8 years, admitted
      to general medical and rehabilitation wards at a tertiary care teaching hospital
      in Halifax, Nova Scotia. No patient refused assessment, and the only exclusion
      criterion was age. INTERVENTIONS: The Hierarchical Assessment of Balance and
      Mobility (HABAM) was completed daily during the first 2 weeks of admission. For
      each patient, frailty status was measured on admission by a Frailty Index based
      on a Comprehensive Geriatric Assessment (FI-CGA). MAIN MEASURES: Death and
      discharge destination. KEY RESULTS: Poor performance in balance, transfers and
      mobility was associated with adverse outcomes. Forty-eight percent of patients
      with the lowest scores in all three domains died, compared with none with the
      highest scores. The relative risk of death for people who deteriorated during the
      first 48 h of admission was 17.1 (95% confidence interval: 4.9-60.3). Changes in
      HABAM scores were related to the discharge destination: patients discharged home
      showed the greatest rate of improvement, whereas those discharged to institutions
      stabilised at a lower level of performance. Fitter patients tended to have better
      performance on admission and faster recovery. CONCLUSIONS: Daily bedside
      observation of mobility and balance allows assessment of acute changes in the
      health of older people. Frailty slows recovery of mobility and balance, and
      reduces recovery potential. By identifying patients most vulnerable to adverse
      outcomes, the HABAM and FI-CGA may facilitate risk stratification in older people
      admitted to hospital.

PMID- 21845490
TI  - The FOUR score predicts outcome in patients after traumatic brain injury.
AB  - BACKGROUND: The most widely used and most studied coma score to date is the
      Glasgow Coma Scale (GCS), which is used worldwide to assess level of
      consciousness and predict outcome after traumatic brain injury (TBI). Our aim was
      to determine whether the Full Outline of UnResponsiveness (FOUR) score is an
      accurate predictor of outcome in TBI patients and to compare its performance to
      GCS. METHODS: We prospectively identified TBI patients admitted to our Neuro-ICU
      between July 2010 and February 2011. We enrolled 51 patients. The FOUR score and
      GCS were determined by one of the investigators. Outcomes were in-hospital
      mortality, and poor neurologic outcome (Glasgow Outcome Scale (GOS) 1-3 and
      Modified Rankin Scale (mRS) score 3-6) at 3-6 months. RESULTS: There was a high
      degree of internal consistency for both the FOUR score (Cronbach's alpha = 0.89)
      and GCS (Cronbach's alpha = 0.85). In terms of predictive power for in-hospital
      mortality, the area under the receiver operating characteristic (ROC) curve was
      0.93 for FOUR score and 0.89 for GCS. In terms of predictive power of poor
      neurologic outcome at 3-6 months, the area under the ROC curve was 0.85 for FOUR
      score and 0.83 for GCS as evidenced by GOS 1-3, and 0.80 for FOUR score and 0.78
      for GCS as evidenced by mRS 3-6. The odds ratio (OR) for in-hospital mortality
      was 0.64 (0.46-0.88) from FOUR score and 0.63 (0.45-0.89) from GCS, for poor
      neurologic outcome was 0.67 (0.53-0.85) from FOUR score and 0.65 (0.51-0.83) from
      GCS for GOS, and was 0.71 (0.57-0.87) from FOUR score and 0.71 (0.57-0.87) from
      GCS for mRS. CONCLUSION: The FOUR score is an accurate predictor of outcome in
      TBI patients. It has some advantages over GCS, such as all components of FOUR
      score but not GCS can be rated in intubated patients.

PMID- 21845489
TI  - Brain tissue oxygen-based therapy and outcome after severe traumatic brain
      injury: a systematic literature review.
AB  - Observational clinical studies demonstrate that brain hypoxia is associated with
      poor outcome after severe traumatic brain injury (TBI). In this study, available
      medical literature was reviewed to examine whether brain tissue oxygen (PbtO2)
      based therapy is associated with improved patient outcome after severe TBI.
      Clinical studies published between 1993 and 2010 that compared PbtO2-based
      therapy combined with intracranial and cerebral perfusion pressure (ICP/CPP)
      based therapy to ICP/CPP-based therapy alone were identified from electronic
      databases, Index Medicus, bibliographies of pertinent articles, and expert
      consultation. For analysis, each selected paper had to have adequate data to
      determine odds ratios (ORs) and confidence intervals (CIs) of outcome described
      by the Glasgow outcome score (GOS). Seven studies that compared ICP/CPP and PbtO2
      to ICP/CPP-based therapy were identified. There were no randomized studies and
      no comparison studies in children. Four studies, published in 2003, 2009, and
      2010 that included 491 evaluable patients were used in the final analysis. Among
      patients who received PbtO2-based therapy, 121(38.8%) had unfavorable and 191
      (61.2%) had a favorable outcome. Among the patients who received ICP/CPP-based
      therapy 104 (58.1%) had unfavorable and 75 (41.9%) had a favorable outcome.
      Overall PbtO2-based therapy was associated with favorable outcome (OR 2.1; 95% CI
      1.4-3.1). Summary results suggest that combined ICP/CPP- and PbtO2-based therapy
      is associated with better outcome after severe TBI than ICP/CPP-based therapy
      alone. Cross-organizational practice variances cannot be controlled for in this
      type of review and so we cannot answer whether PbtO2-based therapy improves
      outcome. However, the potentially large incremental value of PbtO2-based therapy
      provides justification for a randomized clinical trial.

PMID- 21845491
TI  - Gray matters: a deployed physician's perspective on combat medicine in Iraq.
AB  - A female physician who was serving as a first-year medicine resident in Manhattan
      in September 2001 writes this paper. It details her experience of signing up for
      military service as a result of the September 11th attack on the United States.
      She lays out the surroundings, atmosphere, and reactions of those around her
      during the attack and details her own personal motivations for joining the
      military, her need to take control and help those in need heal while also trying
      to heal herself. Grateful, yet haunted by her experience, she provides an
      intimate glimpse into her time serving as a combat physician at a trauma hospital
      in Balad, Iraq during the 2007 military surge. A trained geriatrician and
      palliative care physician she recounts the stories of several patients that have
      forever shaped her life and explores the contradictions and ethical challenges
      she faced while caring for them ultimately struggling with the uncertainty of
      whether what she was truly doing was good for those she served or herself.

PMID- 21845492
TI  - Forming state collaborations to diversify the nation's health workforce: the
      experience of the sullivan alliance to transform the health professions.
AB  - Diversifying the nation's health professions is essential in order to maintain a
      vigorous health workforce, able to respond to the needs of all Americans. The
      inability of the health workforce to keep pace with the changing demographics of
      the nation is a major cause of the persistent inequities in access to quality
      health care for ethnic and racial minorities in the U.S. Ethnic and racial
      minorities have been underrepresented in the genetic counseling profession since
      its inception, despite vigorous professional initiatives to remedy this
      situation. Mittman and Downs published a critical review of these initiatives
      detailing recommendations for change in this journal in 2008. One of their major
      recommendations was the need to learn from, and join, efforts with other health
      professions in seeking to increase professional diversity in genetic counseling.
      This paper reviews new findings on issues impacting health workforce diversity in
      the nation, presents a case study of a national best practice to diversify the
      health workforce and illuminates actions that can be taken by the genetic
      counseling profession. The Sullivan Alliance to Diversify the Health Professions
      is a culmination of two historic initiatives for addressing the dearth of
      minority health professionals and is a national catalyst for increasing diversity
      within the health professions by forging state collaborations among institutions
      of higher education, health professions schools and other key stakeholders.

PMID- 21845493
TI  - Reading between the lines: a comparison of responders and non-responders to a
      family history questionnaire and implications for cancer genetic counselling.
AB  - Family history questionnaires (FHQ) are useful tools for cancer genetic
      counseling, providing an informational basis for pedigree construction and
      individualized cancer risk assessment. Reported return rates of mailed FHQs
      amongst familial cancer clinics that utilize them are lower than desired however,
      and it is unknown whether patients perceive required completion of a FHQ as a
      barrier to access of cancer genetics services. This study critically evaluated
      the use of a mailed FHQ for all routine new patient referrals to a single
      hereditary cancer clinic in Quebec, Canada. Reasons for response/non-response to
      a FHQ and the effect of administration of a questionnaire on patients' self
      reported level of motivation to pursue genetic counseling, were examined. Of 112
      eligible individuals referred during the study period, 86 completed a semi
      structured telephone survey; of these, 45% had returned the mailed FHQ prior to
      the telephone survey (Responders) and 55% had not (Non-responders). Overall, the
      majority of participants indicated a FHQ is an acceptable and understandable
      method of collecting family history information. Most prevalent reasons for not
      returning the FHQ were (bad) timing (56%), and difficulty accessing family
      history information (46%). Non-response was significantly associated with
      difficulty in asking relatives for the requested information (p = 0.011), and Non
      responders cited fewer overall perceived benefits of cancer genetic counseling as
      compared with Responders (p < 0.0001). One quarter of Non-responders returned the
      mailed FHQ following administration of the telephone survey, suggesting
      implementation of a follow-up prompt is a cost-effective way to increase
      response.

PMID- 21845494
TI  - HER2-positive gastric cancer.

PMID- 21845495
TI  - Inverse association between miR-194 expression and tumor invasion in gastric
      cancer.
AB  - BACKGROUND: MiR-194 has been shown to be specifically expressed in the human
      gastrointestinal tract and may play an antimetastatic role in primary liver
      cancer cells. However, the role of miR-194 in gastric cancer is still unclear.
      METHODS: Total RNA was extracted from tissues of 119 patients with gastric cancer
      and three gastric cancer cell lines (SGC-7901, MGC-803, and BGC-823). Expression
      levels of miR-194 were determined by real-time polymerase chain reaction (PCR).
      Moreover, a MTT proliferation assay and transwell cell invasion assay were
      performed to study the effect of miR-194 on SGC-7901 cell proliferation and
      invasion. Finally, we used real-time PCR and western blot to verify which gene
      was the target of miR-194 in gastric cancer. RESULTS: Though there was no
      significant difference between cancerous and matching noncancerous tissues, we
      found patients with lower expression of miR-194 tended to have larger tumor size
      (P = 0.002) and more advanced pT stage (P = 0.028) in gastric cancer. Moreover,
      the expression of miR-194 was significantly lower in Borrmann IV type gastric
      cancer than in Borrmann I, II, and III types (P = 0.019). Furthermore, an in
      vitro invasion assay indicated that the penetrated cell intensity after miR-194
      mimics transfection was significantly lower than the control. However,
      overexpression of miR-194 had little effect on the SGC-7901 cell cycle and
      proliferation. The results of real-time PCR and western blot highlighted that miR
      194 interacted with N-cadherin and negatively regulated its expression at the
      translational level. CONCLUSION: These findings imply that miR-194 might play an
      important role in gastric cancer invasion and progression.

PMID- 21845496
TI  - Comparison of clinicopathologic factors in 122 patients with resected pancreatic
      and ileal neuroendocrine tumors from a single institution.
AB  - BACKGROUND: Recent population-based studies have demonstrated significant
      differences in outcome between patients with pancreatic and ileal neuroendocrine
      tumors. The objective of this study was to examine the clinicopathologic
      differences between ileal and pancreatic neuroendocrine tumors following
      resection. METHODS: A retrospective chart review was performed and data on
      clinicopathologic variables, biochemical markers, and follow-up of patients with
      resected ileal (INETs) and pancreatic (PNETs) neuroendocrine tumors were
      collected. The t test or analysis of variance (ANOVA) was used to compare means.
      Survival analysis was performed using the Kaplan-Meier method. RESULTS: Between
      1998 and 2010, 122 patients with PNETs and INETs were explored (70 PNETs and 52
      INETs). Several variables were found to be significantly different between
      patients in both groups. INETs were more often associated with flushing (44 vs.
      14%; P < 0.001) and diarrhea (63 vs. 16%; P < 0.001) and were more often
      associated with elevation in preoperative serum levels of pancreastatin (88 vs.
      42%; P < 0.001), chromogranin A (78 vs. 54%; P = 0.036), and serotonin (90 vs.
      43%; P < 0.001). INETs more frequently had vascular invasion on pathology (96 vs.
      60%; P < 0.001), and presented more often with nodal and/or distant metastases
      (77 vs. 37%; P < 0.001). There was no significant difference in overall survival
      between patients in both groups. CONCLUSION: In this series, patients with INETs
      presented with a more advanced stage of disease compared with PNETs, had higher
      preoperative levels of 3 markers, and were more often symptomatic. Despite these
      factors, there was no significant difference in overall survival between patients
      with these 2 tumor types.

PMID- 21845497
TI  - Soluble CXCL16 in preoperative serum is a novel prognostic marker and predicts
      recurrence of liver metastases in colorectal cancer patients.
AB  - PURPOSE: This study was designed to identify novel and reliable serum prognostic
      markers in patients with colorectal cancer (CRC). METHODS: Based on cytokine
      array analysis, we identified soluble CXCL16 as a novel prognostic serum marker.
      Serum levels of CXCL16 were assessed in 314 CRC patients and 20 normal volunteers
      by enzyme-linked immunosorbent assay, and their relationships with
      clinicopathologic findings, including survival, were investigated. Proliferation,
      invasion, and wound healing assays were used to investigate the biological role
      of soluble CXCL16 in CRC cells, by exposure of HT-29 cells to recombinant CXCL16.
      RESULTS: The median serum CXCL16 concentration in CRC patients was significantly
      higher than that in normal volunteers. In addition, serum CXCL16 levels increased
      significantly in accordance with the progression of UICC stage classification.
      Elevated serum CXCL16 level was significantly associated with poor survival and
      was an independent prognostic marker in CRC patients. Furthermore, in stage I-III
      CRC patients who underwent curative intent surgery, elevated serum CXCL16 levels
      were significantly associated with metachronous liver recurrence and poor
      survival. Recombinant soluble CXCL16 promoted the epithelial-mesenchymal
      transition (EMT) phenotype characterized by impaired E-cadherin production and
      induction of vimentin in vitro. In addition, recombinant soluble CXCL16 promoted
      cell growth, migration, and invasion in a CRC cell line. CONCLUSIONS: In this
      study, we identified CXCL16 as a novel prognostic marker. Preoperative high serum
      levels of CXCL16 were associated with metachronous liver recurrence and poor
      prognosis in CRC patients. Soluble CXCL16 may play an important role in liver
      metastases through the induction of EMT.

PMID- 21845498
TI  - Skin-sparing mastectomy and immediate autologous breast reconstruction in locally
      advanced breast cancer patients: a UBC perspective.
AB  - PURPOSE: To describe the clinical outcomes of patients with locally advanced
      breast cancer (LABC) receiving neoadjuvant chemotherapy and preoperative
      radiotherapy, followed by skin-sparing mastectomy (SSM) and immediate autologous
      breast reconstruction (IABR). METHODS: A retrospective review of 30 LABC patients
      who underwent SSM and IABR between 1997 to 2007 was performed. Data were drawn
      from patient records and the University of British Columbia (UBC) Breast
      Reconstruction and British Columbia Cancer Agency databases. RESULTS: All 30
      patients received neoadjuvant chemotherapy, preoperative radiotherapy, SSM, and
      IABR. Fifteen patients (50%) had stage IIIA disease, 13 (43%) stage IIIB, and 2
      (6.7%) stage IIIC. Reconstruction types included the pedicled transverse rectus
      myocutaneous flap (n = 24), the latissimus dorsi flap (n = 5), and a combination
      of transverse rectus myocutaneous and latissimus dorsi flap (n = 1). The median
      follow-up was 3.51 years (range 1-9.4 years). Local complications included
      mastectomy flap necrosis (n = 3), partial flap necrosis (n = 1), fat necrosis (n
      = 1), seroma (n = 3), infection (n = 2), and flap fibrosis (n = 1). The incidence
      of donor site complications was 20%. Overall 5-year actuarial locoregional
      relapse-free, distant relapse-free, and disease-specific survival rates were 80,
      65, and 68%, respectively. Excellent or good physician-rated aesthetic results
      were achieved in 66% of patients. CONCLUSIONS: The UBC protocol avoids
      irradiation of the autologous breast reconstruction. Outcomes compare with
      findings from similar studies with respect to local recurrence, distant relapse,
      overall survival, and surgical complication rates. Neoadjuvant chemotherapy and
      preoperative radiotherapy in LABC patients desiring autologous breast
      reconstruction can be considered a safe option.

PMID- 21845499
TI  - Strategy for nonresponder breast cancer patients to neoadjuvant treatment.

PMID- 21845500
TI  - Sinusoidal obstruction syndrome impairs long-term outcome of colorectal liver
      metastases treated with resection after neoadjuvant chemotherapy.

PMID- 21845501
TI  - Teaching children with dyslexia to spell in a reading-writers' workshop.
AB  - To identify effective treatment for both the spelling and word decoding problems
      in dyslexia, 24 students with dyslexia in grades 4 to 9 were randomly assigned to
      treatments A (n=12) or B (n=12) in an after-school reading-writers' workshop at
      the university (thirty 1-h sessions twice a week over 5 months). First, both
      groups received step 1 treatment of grapheme-phoneme correspondences (gpc) for
      oral reading. At step 2, treatment A received gpc training for both oral reading
      and spelling, and treatment B received gpc training for oral reading and
      phonological awareness. At step 3, treatment A received orthographic spelling
      strategy and rapid accelerated reading program (RAP) training, and treatment B
      continued step 2 training. At step 4, treatment A received morphological
      strategies and RAP training, and treatment B received orthographic spelling
      strategy training. Each treatment also had the same integrated reading-writing
      activities, which many school assignments require. Both groups improved
      significantly in automatic letter writing, spelling real words, compositional
      fluency, and oral reading (decoding) rate. Treatment A significantly outperformed
      treatment B in decoding rate after step 3 orthographic training, which in turn
      uniquely predicted spelling real words. Letter processing rate increased during
      step 3 RAP training and correlated significantly with two silent reading fluency
      measures. Adding orthographic strategies with "working memory in mind" to phonics
      helps students with dyslexia spell and read English words.

PMID- 21845502
TI  - Population composition, public policy, and the genetics of smoking.
AB  - In this article, we explore the effect of public policy on the extent to which
      genes influence smoking desistance. Using a sample of adult twins (n(mz) = 363,
      n(dz) = 233) from a large population registry, we estimate Cox proportional
      hazards models that describe similarity in the timing of smoking desistance among
      adult twin pairs. We show that identical twin pairs are significantly more likely
      to quit smoking within a similar time frame compared with fraternal twin pairs.
      Importantly, we then show that genetic factors for smoking desistance increase in
      importance following restrictive legislation on smoking behaviors that occurred
      in the early and mid-1970s. These findings support the social push perspective
      and make important contributions to the social demography and genetic
      epidemiology of smoking as well as to the gene-environment interaction
      literatures.

PMID- 21845503
TI  - Prevalence of questioning regarding life-sustaining treatment and time
      utilisation by forgoing treatment in francophone PICUs.
AB  - PURPOSE: Our goal is to assess the prevalence of questioning about the
      appropriateness of initiating or maintaining life-sustaining treatments (LST) in
      French-speaking paediatric intensive care units (PICUs) and to evaluate time
      utilisation related to decision-making processes (DMP). METHODS: 18-month,
      multicentre, prospective, descriptive, observational study in 15 French-speaking
      PICUs. RESULTS: Among the 5,602 children admitted, 410 died (7.3%), including 175
      after forgoing LST (42.7% of deaths). LST was questioned in 308 children (5.5%)
      with a prevalence of 13.3 per 100 patient-days. More than 30% of children
      survived despite the appropriateness of LST being questioned (23% despite a
      decision to forgo treatment). Median caregiver time spent on making and
      presenting the decisions was 11 h per child. CONCLUSIONS: In this study, on any
      given day in each 10-bed PICU, there was more than one child for whom a DMP was
      underway. Of children, 23% survived despite a decision to forgo LST being made,
      which underlines the need to elaborate a care plan for these children. Also, DMP
      represented a large amount of staff time that is undervalued but necessary to
      ensure optimal palliative practice in PICU.

PMID- 21845504
TI  - Factors associated with increased risk of readmission to intensive care in
      Australia.
AB  - PURPOSE: To determine the epidemiology, in-hospital mortality, trends, patient
      characteristics and predictors of intensive care unit (ICU) readmission in
      Australia. METHODS: A retrospective longitudinal study of data for 38 Australian
      ICUs extracted from the Australian and New Zealand Intensive Care Society Adult
      Patient Database (ANZICS-ADP) for the years 2000-2007. Demographic, diagnostic,
      physiological and outcome data were analysed. A multivariate model was
      constructed to identify risk factors for ICU readmission. Outcomes examined
      included observed and risk-adjusted in-hospital mortality. RESULTS: A total of
      247,103 patients were discharged alive from their first ICU admission; 13,598
      (5.5%) were readmitted at least once. Variables associated with an odds ratio
      greater than 1.05 for readmission (p < 0.001) were an initial ICU admission
      source other than elective surgery, any chronic health variable on severity
      scoring, tertiary hospital ICU and discharge between 6 p.m. and 6 a.m. Five
      initial diagnoses were associated with an odds ratio (OR) greater than 2 for
      readmission (p < 0.001). In-hospital mortality in readmitted patients was 20.7%
      compared with 4.4% in those not readmitted. Readmission rates have not changed
      over the study period. After adjustment for illness severity and readmission
      propensity, ICU readmission remained significantly associated with in-hospital
      mortality (OR 5.4, 95%, confidence interval (CI) 5.1-5.7). CONCLUSIONS: Many risk
      factors for increased ICU readmission were identified in this study including ICU
      discharge between 6 p.m. and 6 a.m. This was the only modifiable variable
      studied. Prospective studies are required to identify other factors and to
      determine whether interventions may reduce ICU readmission and its high
      associated in-hospital mortality.

PMID- 21845505
TI  - Palmitoyl ascorbate liposomes and free ascorbic acid: comparison of anticancer
      therapeutic effects upon parenteral administration.
AB  - PURPOSE: To evaluate and compare anticancer therapeutic effect of palmitoyl
      ascorbate liposomes (PAL) and free ascorbic acid (AA). METHODS: Liposomes
      incorporating palmitoyl ascorbate (PA) were prepared and evaluated for PA content
      by HPLC. To elucidate mechanism of action of cell death in vitro, effect of
      various H(2)O(2) scavengers and metal chelators on PA-mediated cytotoxicity was
      studied. Effect of various combinations of PAL and free AA on in vitro
      cytotoxicity was evaluated on 4T1 cells. In vivo, PAL formulation was modified
      with polyethylene glycol; effect of PEGylation on in vitro cytotoxicity was
      evaluated. Biodistribution of PEG-PAL formulation was investigated in female
      Balb/c mice bearing murine mammary carcinoma (4T1 cells). In vivo anticancer
      activity of PEG-PAL (PEG-PAL equivalent to 20 mg/kg of PA injected intravenously
      on alternate days) was compared with free AA therapy in same model. RESULTS: PEG
      PAL treatment was significantly more effective than free AA treatment in slowing
      tumor growth. CONCLUSIONS: Nanoparticle formulations incorporating PA can kill
      cancer cells in vitro. The mechanism of PA cytotoxicity is based on production of
      extracellular reactive oxygen species and involves intracellular transition
      metals.

PMID- 21845506
TI  - Prediction of the mechanical behaviour of crystalline solids.
AB  - PURPOSE: To explore the use of crystal inter-planar d-spacings and slip-plane
      interaction energies for predicting and characterising mechanical properties of
      crystalline solids. METHODS: Potential relationships were evaluated between
      mechanical properties and inter-planar d-spacing, inter-planar interaction
      energy, and dispersive surface energy as determined using inverse gas
      chromatography (IGC) for a set of pharmaceutical materials. Inter-planar
      interaction energies were determined by molecular modelling. RESULTS: General
      trends were observed between mechanical properties and the largest inter-planar d
      spacing, inter-planar interaction energies, and IGC dispersive surface energy. A
      number of materials showed significant deviations from general trends. Weak
      correlations and outliers were rationalised. CONCLUSIONS: Results suggest that
      the highest d-spacing of a material could serve as a first-order indicator for
      ranking mechanical behaviour of pharmaceutical powders, but with some
      reservation. Inter-planar interaction energy normalised for surface area shows
      only a weak link with mechanical properties and does not appear to capture
      essential physics of deformation. A novel framework linking mechanical properties
      of crystals to the distinct quantities, slip-plane energy barrier and inter
      planar interaction (detachment) energy is proposed.

PMID- 21845507
TI  - Elucidation of degradants in acidic peak of cation exchange chromatography in an
      IgG1 monoclonal antibody formed on long-term storage in a liquid formulation.
AB  - PURPOSE: An IgG1 therapeutic monoclonal antibody showed an increase in acidic or
      pre-peak by cation exchange chromatography (CEX) at elevated temperatures, though
      stable at 2-8 degrees C long-term storage in a liquid formulation.
      Characterization effort was undertaken to elucidate the degradants in CEX pre
      peak and effect on biological activity. METHODS: Purified CEX fractions were
      collected and analyzed by peptide mapping, size exclusion, intact and reduced
      alkylated reversed phase techniques. Biophysical characterization, isoelectric
      focusing and Isoquant analysis were also performed to determine nature of
      degradants. Bioassay and surface plasmon resonance experiments were performed to
      determine the impact on biological activity of the degradants. RESULTS: No major
      degradation due to oxidation, clipping or aggregation was detected;
      conformational differences between purified fractions observed were not
      significant. Sialic acid, N-terminal glutamine cyclization and glycation
      differences contributed to the CEX pre-peak in the mAb control sample; increase
      in CEX pre-peak at 25 degrees C and higher was caused by additive degradation
      pathways of deamidation, related isomerization and clipping. CONCLUSIONS: The
      observed CEX pre-peak increase was caused by multiple degradations, especially
      deamidation and clipping. This elucidation of degradants in CEX peaks may apply
      to other therapeutic IgG1 monoclonal antibodies.

PMID- 21845508
TI  - Comparison of late complications of retropubic and transobturator slings in
      stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: To compare the late complication profiles between
      retropubic and transobturator slings used for stress urinary incontinence was the
      objective of the study. METHODS: Between the years 2003 and 2010, 338
      complications of midurethral slings were surgically managed in a tertiary
      referral center. For the purpose of study, we excluded slings that had materials
      other than monofilament polypropylene, patients with previous anti-incontinence
      surgeries, and patients who were suspected of having a neurologic bladder
      condition. This is a prospective and retrospective study of the complications of
      midurethral slings. The characteristics of complications in retropubic and
      transobturator routes were compared and analyzed. RESULTS: Two hundred eighty
      cases with midurethral sling complications were suitable for analysis. Of these,
      retropubic slings constituted 210 and transobturator 70. The time interval
      between the insertion of tape and onset of complications was similar in both
      groups. Within the two groups, obstructive symptoms were seen more frequently in
      the retropubic tapes group. Compared to the retropubic tapes group, the
      transobturator group had more number of complications related to persistent pain
      (10% tension-free vaginal tapes vs. 32% transobturator tapes), dyspareunia (3%
      vs. 18%), and tape-related infections (4% vs. 18%). There were no significant
      differences among the complication rates pertaining to de novo overactive bladder
      (49% vs. 44%), obstructive symptoms (48% vs. 30%), and contraction of sling
      material (5% vs. 8%). CONCLUSIONS: Obstructive complications were seen more
      commonly in the retropubic tapes compared to the transobturator tapes.
      Transobturator tapes were more frequently associated with persistent pain,
      dyspareunia, and tape-related infections as compared to retropubic tapes.

PMID- 21845509
TI  - Paget-Schroetter syndrome treated with cutting-balloon angioplasty.
AB  - Here, a case of Paget-Schroetter Syndrome in a 25-year-old guitar player is
      reported. After thrombolysis, conventional angioplasty failed to dilate the
      underlying subclavian stenosis both before and after first-rib excision with
      scalenus anterior and medius division. For the third attempt at angioplasty, a
      cutting balloon was used, which immediately produced a good result. Venography at
      4-year follow-up showed no restenosis and no functional deficit. This case report
      demonstrates that cutting-balloon angioplasty may be considered when conventional
      balloon fails and may have greater durability than conventional balloon
      angioplasty in the treatment of Paget-Schroetter syndrome.

PMID- 21845510
TI  - A sweet heart: increased cardiac glucose uptake in patients with lipoprotein
      lipase deficiency.

PMID- 21845511
TI  - Outcomes of right vs. left colectomy for colon cancer.
AB  - BACKGROUND: Right colectomy (RC) is generally believed to be a simpler operation
      with better outcomes than left colectomy (LC). Our study was primarily intended
      to compare patient characteristics and perioperative outcomes between RC and LC
      in colon cancer patients, and secondarily to identify factors that increase the
      risk of developing postoperative abdominal abscess and/or anastomotic leak.
      METHODS: Using the 2007 Nationwide Inpatient Sample database, we evaluated
      patients who underwent elective RC and LC for colon cancer. RESULTS: A total of
      50,799 patients underwent elective RC and LC for malignancy during 2007 (RC,
      63.5%; LC, 36.5%). Overall, 9.6% were performed laparoscopically (RC, 9.7% vs.
      LC, 9.5%, P = 0.39). The majority of patients were Caucasian; 54.2% of RC and
      46.5% LC patients were female (P < 0.01). RC patients were older (mean age, 70.8
      vs. 65.8 years, P < 0.01) and had more comorbidities. While LC had more overall
      intraoperative complications (RC, 0.30% vs. LC, 1.32%, P < 0.01), RC had higher
      overall incidence of postoperative complications (28.43% vs. 26.75%, P < 0.01).
      Mean length of hospital stay (RC, 7.37 days vs. LC, 7.38 days) and in-hospital
      mortality (RC, 1.37% vs. LC, 1.49%) were similar in both groups. Multivariate
      analysis identified Native American race [adjusted odd ratio (AOR), 2.02],
      chronic renal failure (AOR, 1.97), congestive heart failure (AOR, 1.72), chronic
      pulmonary disease (AOR, 1.40), metastatic disease (AOR, 1.34), male gender (AOR,
      1.23), and LC (AOR, 1.12) all independently increased the risk of abscess and/or
      leak. CONCLUSIONS: RC patients were older and had more comorbidities and
      postoperative complications. Patient characteristics and comorbidities were more
      important in determining overall postoperative complications than anastomotic
      types.

PMID- 21845512
TI  - Conservative management of isolated sectoral duct injury with bile leak (type C
      injury): important and essential initial step in the management, not an option.

PMID- 21845513
TI  - How to teach uncommon and highly complex operations.
AB  - The Surgical Council on Resident Education (SCORE) was officially formed by six
      surgical organizations in 2006 with the goal of improving general surgery
      residency training through the development of an explicit curriculum. As a
      result, SCORE has identified a group of "essential" operations which believes
      that residents should be competent to perform by the end of training. Other
      "complex" operations require additional training beyond residency. Currently,
      operative data submitted by residents suggest that there are significant gaps
      between ideal and actual operative experience. A particularly difficult challenge
      is to train residents to perform procedures that are rarely encountered.

PMID- 21845514
TI  - Pilot study of adjuvant chemotherapy with 3-week combination of S-1 and cisplatin
      for patients with stage II-IV (M0) gastric cancer.
AB  - PURPOSE: The feasibility of a 3-week combination of S-1 and cisplatin as an
      adjuvant chemotherapy for patients with curatively resected gastric cancer was
      investigated. EXPERIMENTAL DESIGN: Korean patients with stage II-IV (M0) gastric
      adenocarcinoma who underwent a gastrectomy with D2 lymph node resection were
      enrolled. The S-1 was administered orally at 80 mg/m(2) divided into two daily
      doses for 14 days, while the cisplatin was administered at 60 mg/m(2)
      intravenously over 2 h every 21 days. The patients received a maximum of six
      cycles. RESULTS: From January 2006 to July 2010, 74 patients were included in
      this study. The median patient age was 56 years (range, 22-71), and 51.4% (38/74)
      of the patients had a performance status of 0. The median number of chemotherapy
      cycles administered was 6 (range, 1-6). The median relative dose intensity was
      86.4% for S-1 and 80.0% for cisplatin. With a median follow-up duration of 13.9
      months, the median relapse-free survival (RFS) and overall survival (OS) have not
      yet been reached. Fifteen relapses (20.3%) were documented. Plus, the estimated
      RFS rate was 60.5% at 3 years. The treatments were generally well tolerated. The
      most frequently observed grade 3-4 hematological toxicity was neutropenia
      (35.1%), and only 1 cycle of neutropenic fever occurred. The most frequently
      observed grade 3-4 non-hematological toxicities were nausea (4.1%) and asthenia
      (4.1%), and all the other grade 3-4 non-hematological toxicities were observed in
      less than 3% of the patients. CONCLUSIONS: Postoperative adjuvant S-1 plus
      cisplatin for 18 weeks was found to be feasible for patients with stage II-IV
      (M0) gastric adenocarcinoma following complete surgical resection.

PMID- 21845515
TI  - Immunosuppressive effects and mechanisms of leflunomide in dengue virus infection
      of human dendritic cells.
AB  - BACKGROUND: Dengue virus (DENV) infection is a serious public health issue
      without specific treatment. We examined the potential immunomodulatory effects of
      leflunomide, a dihydroorotate dehydrogenase inhibitor commonly prescribed for
      arthritis, in DENV-stimulated monocyte-derived dendritic cells (mo-DCs). METHODS:
      mo-DCs were prepared from purified monocytes. Cytokine and chemokine
      concentrations were determined by enzyme-linked immunosorbent assay. Expression
      of cell surface markers or viral E protein was measured by flow cytometry. The
      activation of transcription factors and kinases was determined by electrophoretic
      mobility shift assays, Western blotting, or immunoprecipitation kinase assays.
      Chemotaxis assays were used to determine cell migration. RESULTS: Leflunomide at
      therapeutic concentrations inhibited cytokine and chemokine production from DENV
      infected mo-DCs. Leflunomide suppressed mo-DC maturation by downregulating the
      expression of both CD80 and CD86. In addition, leflunomide inhibited DENV-induced
      mo-DC migration and mo-DC response to chemoattractants CCL19 and CCL21.
      Inhibition of mo-DC migration was likely due to the suppression of CCR7
      expression on mo-DCs. These events were associated with the suppression of
      nuclear factor kappa B and activator protein-1 signaling pathways by leflunomide.
      CONCLUSIONS: Leflunomide preserves immunosuppressive effects, inhibiting
      activation of DENV-stimulated mo-DCs. Leflunomide may be helpful in the
      development of therapeutics for DENV infection.

PMID- 21845516
TI  - Altered phenotype and functionality of circulating immune cells characterize
      adult patients with nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is a chronic inflammatory liver disease
      associated with insulin resistance and its metabolic consequences. Leukocyte
      mobilization, intrahepatic activation, and an exacerbated production of reactive
      oxygen species (ROS) and cytokines contribute to the development of NASH. Though
      alterations in peripheral blood (PB) T cell proportions and functionality remain
      unidentified, they might play a main role in NASH progression. We have compared
      the phenotype and Th1/Th2 commitment of peripheral immune cell reservoirs in
      adult patients and controls as well as the ability of neutrophils and monocytes
      to handle an ex vivo challenge. Also, we correlated those parameters with the
      main histological characteristics in NASH. Compared with controls, patients
      showed increased numbers of CD4(+) cells and both CD4(+) and CD8(+) CD45RO
      subsets together with a higher frequency of IFN-gamma-producing CD4(+) and CD8(+)
      T cells. We also found a decreased number of CD4(+) and CD8(+) CD45RA subsets.
      The distinctive production of IFN-gamma highlights the significance of the
      observed skewed frequencies of PB T cells. Whereas ROS production by monocytes
      from NASH patients did not differ from controls, circulating neutrophils
      displayed a particularly higher phorbol myristate acetate-induced production of
      ROS. A negative correlation between oxidative burst and fibrosis grade was
      observed. This study reveals the presence of a characteristic profile of
      peripheral immune cells in NASH. We also discuss the probable influence of
      obesity on some of our present findings.

PMID- 21845521
TI  - Air quality as respiratory health indicator: a critical review.
AB  - As part of the European Public Health project IMCA II validity and practicability
      of "air pollution" as a respiratory health indicator were analyzed. The
      definitions of air quality as an indicator proposed by the WHO project ECOEHIS
      and by IMCA I were compared. The public availability of the necessary data was
      checked through access to web-based data-bases. Practicability and interpretation
      of the indicator were discussed with project partners and external experts. Air
      quality serves as a kind of benchmark for the good health-related environmental
      policy. In this sense, it is a relevant health indicator. Although air quality is
      not directly in the responsibility of health policy, its vital importance for the
      population's health should not be neglected. In principle, data is available to
      calculate this IMCA indicator for any chosen area in Europe. The indicator is
      relevant and informative, but calculation and interpretation need input from
      local expert knowledge. The European health policy is well advised to take air
      quality into account. To that end, an interdisciplinary approach is warranted.
      The proposed definition of air quality as a (respiratory) health indicator is
      workable, but correct interpretation depends on expert and local knowledge.

PMID- 21845517
TI  - 3beta-Hydroxysterol-Delta24 reductase plays an important role in long bone growth
      by protecting chondrocytes from reactive oxygen species.
AB  - Desmosterolosis is an autosomal recessive disease caused by mutations in the
      3beta-hydroxysterol-Delta24 reductase (DHCR24) gene, with severe developmental
      anomalies including short limbs. We utilized DHCR24 knockout (KO) mice to study
      the underlying bone pathology. Because the KO mice died within a few hours after
      birth, we cultured metatarsal bones from newborn mice. The growth of bones from
      KO mice was significantly retarded after 1 week of culture. Absence of
      proliferating chondrocytes in the growth plate and abnormal hypertrophy of
      prehypertrophic chondrocytes were observed in the bones from KO mice.
      Hypertrophic differentiation was evidenced by higher expression of Indian
      hedgehog, alkaline phosphatase, and matrix metalloproteinase 13. Since elevated
      levels of reactive oxygen species (ROS) during chondrogenesis are known to
      inhibit proliferation and to initiate chondrocyte hypertrophy in the growth
      plate, and since DHCR24 acts as a potent ROS scavenger, we hypothesized that the
      abnormal chondrocyte proliferation and differentiation in KO mice were due to
      decreased ROS scavenging activity. Treatment with an antioxidant, N-acetyl
      cysteine, could correct the abnormalities observed in the bones from KO mice.
      Treatment of bones from wild-type mice with U18666A, a chemical inhibitor of
      DHCR24, resulted in short broad bones with a disrupted proliferating zone.
      Treatment of ATDC cells with hydrogen peroxide (H(2)O(2)) induced hypertrophic
      changes as evidenced by the expression of the marker genes specific for
      hypertrophic chondrocyte differentiation. H(2)O(2)-induced hypertrophic change
      was prevented by adenoviral delivery of DHCR24. Induction of chondrocyte
      differentiation in ATDC cells by insulin was associated with increased ROS
      production that was markedly enhanced by treatment of ATDC5 cells with DHCR24
      siRNA. This is the first demonstration that DHCR24 plays an important role in
      long bone growth by protecting chondrocytes from ROS.

PMID- 21845522
TI  - Case-crossover design: air pollution and health outcomes.
AB  - OBJECTIVES: The objective of this study was to investigate variants of case
      crossover design for assessing correlations between counts of health events over
      time and exposure to ambient air pollution. For illustrative purposes, daily
      emergency department (ED) visits for depression among females were considered.
      MATERIALS AND METHOD: Ambient nitrogen dioxide (NO(2)) was used as a principal
      ambient air pollutant. In addition, sulphur dioxide (SO(2)) and carbon monoxide
      (CO) were considered. Different configurations of the control periods (every 1,
      2, ..., 10 days) and different forms (linear, natural splines) of meteorological
      factors in the applied conditional logistic regression models were used. The
      sequence of overlapping age intervals was defined ([0, 19], [1, 20], and so on)
      and each age group was analyzed separately. The results for the defined age
      sequences allow identifying age ranges in which the effects are strongest.
      RESULTS: Consequently, for example, different age ranges for patients for which
      ED visits for depression were correlated with NO(2) and SO(2) were identified.
      This age-interval difference explains the very often observed phenomenon whereby
      two air pollutants used in one model may not show correlations with health
      outcomes. In this situation they affect separate age groups. The results also
      show dependency on number-defined control periods for the applied case-crossover
      technique. The opposite statistical conclusions may be generated by using
      different control schemas. CONCLUSIONS: The results support the hypothesis that
      ED visits for depressive disorder may be correlated with exposure to ambient air
      pollution.

PMID- 21845523
TI  - Comparison of the level of aggression towards healthcare workers within Podlaskie
      Voivodeship.
AB  - OBJECTIVES: The aim of this study was to estimate the level of exposure and
      average intensity of aggression towards particular professional groups of
      healthcare workers. MATERIALS AND METHODS: Study participants (n = 1498) were
      employed at open and closed healthcare units within Podlaskie Voivodeship: 493
      nurses, 504 midwives and 501 physicians. The MDM Questionnaire was applied.
      RESULTS: Aggression originating from patients was experienced by 92% of nurses,
      86% of doctors, and 74% of midwives examined. Aggressive behavior of co-working
      physicians concerned 55% of midwives, 54% of nurses and 40% of physicians. The
      highest average levels of patient aggression, ranging between 2.20 and 3.31, were
      reported by nurses. CONCLUSIONS: Nurses are the group most exposed to most
      aggression forms and sources. Physicians are least exposed to aggression, except
      for aggression manifested by patients.

PMID- 21845524
TI  - Effects of kinesio taping in a physical therapist with acute low back pain due to
      patient handling: a case report.
AB  - OBJECTIVES: The paper describes the case of a physical therapist with acute Low
      Back Pain (LBP) due to patient handling and the efficacy of Kinesio Taping (KT)
      around the trunk in the treatment of this occupational LBP. MATERIALS AND
      METHODS: KT was applied around the trunk for 3 days, for an average of 10 h/day.
      Kinesio tape was applied with 130-140% stretch to the rectus abdominis, internal
      oblique, erector spinae, and latissimus dorsi muscles, which are activated in the
      process of lifting. RESULTS: Following the KT application, the 'Visual Analog
      Scale' and 'Oswestry Disability Questionnaire scores' gradually decreased and
      active trunk range of motion limited by the LBP increased progressively. The
      physical therapist no longer complained of LBP and was able to handle patients
      without any pain. CONCLUSIONS: Hence, continuous application of KT around the
      trunk may be a supplementary treatment method for acute LBP in physical
      therapists and enable continuous patient handling without any loss of work time
      due to occupational LBP. In addition, KT may also be applicable for the
      prevention and treatment of occupational LBP in other professions involving
      lifting heavy objects.

PMID- 21845525
TI  - [Life is moving. Abstracts of the 22nd German Geriatric Congress of the German
      Society for Geriatrics. September 22-24, 2011. Klinikum Bad Branstedt, Germany].

PMID- 21845526
TI  - Spectrophotometric quantification of lactose in solution with a peroxidase-based
      enzymatic cascade reaction system.
AB  - A spectrophotometric assay was developed for the quantification of lactose in
      aqueous solution via a one-pot enzymatic cascade reaction at 25  degrees C and pH
      7.2. Lactose (0.2-1.8 mM), E. coli beta-galactosidase (beta-Gal), Aspergillus
      niger glucose oxidase (GOD), horseradish peroxidase (HRP) and o-phenylenediamine
      (OPD) were incubated, and the increase in absorbance at 417 nm (A (417)) due to
      the formation of DAP (2,3-diaminophenazine), the dimeric oxidation product of
      OPD, was followed. The increase in A (417) was found to depend linearly on the
      initial lactose concentration via three consecutive but simultaneously occurring
      enzymatic reaction steps catalyzed by beta-Gal, GOD, and HRP. No pre-incubation
      of lactose with beta-Gal is needed with this simple lactose assay.

PMID- 21845527
TI  - Microchip-based cellular biochemical systems for practical applications and
      fundamental research: from microfluidics to nanofluidics.
AB  - By combining cell technology and microchip technology, innovative cellular
      biochemical tools can be created from the microscale to the nanoscale for both
      practical applications and fundamental research. On the microscale level, novel
      practical applications taking advantage of the unique capabilities of
      microfluidics have been accelerated in clinical diagnosis, food safety,
      environmental monitoring, and drug discovery. On the other hand, one important
      trend of this field is further downscaling of feature size to the 10(1)-10(3) nm
      scale, which we call extended-nano space. Extended-nano space technology is
      leading to the creation of innovative nanofluidic cellular and biochemical tools
      for analysis of single cells at the single-molecule level. As a pioneering group
      in this field, we focus not only on the development of practical applications of
      cellular microchip devices but also on fundamental research to initiate new
      possibilities in the field. In this paper, we review our recent progress on
      tissue reconstruction, routine cell-based assays on microchip systems, and
      preliminary fundamental method for single-cell analysis at the single-molecule
      level with integration of the burgeoning technologies of extended-nano space.

PMID- 21845528
TI  - Multivariate classification of pigments and inks using combined Raman
      spectroscopy and LIBS.
AB  - The authenticity of objects and artifacts is often the focus of forensic analytic
      chemistry. In document fraud cases, the most important objective is to determine
      the origin of a particular ink. Here, we introduce a new approach which utilizes
      the combination of two analytical methods, namely Raman spectroscopy and laser
      induced breakdown spectroscopy (LIBS). The methods provide complementary
      information on both molecular and elemental composition of samples. The potential
      of this hyphenation of spectroscopic methods is demonstrated for ten blue and
      black ink samples on white paper. LIBS and Raman spectra from different inks were
      fused into a single data matrix, and the number of different groups of inks was
      determined through multivariate analysis, i.e., principal component analysis,
      soft independent modelling of class analogy, partial least-squares discriminant
      analysis, and support vector machine. In all cases, the results obtained with the
      combined LIBS and Raman spectra were found to be superior to those obtained with
      the individual Raman or LIBS data sets.

PMID- 21845529
TI  - Studying pigments on painted plaster in Minoan, Roman and early Byzantine Crete.
      A multi-analytical technique approach.
AB  - Wall paintings spanning two millennia of Cretan painting history and technology
      were analysed in an effort to determine similarities and evolutions of painting
      materials and technology. A multi-technique approach was employed that combined
      the use of (a) laser-induced breakdown spectroscopy (LIBS) and Raman
      microspectroscopy, based on mobile instrumentation, appropriate for rapid,
      routine-level object characterization, and (b) non-destructive X-ray
      diffractometry (XRD), performed directly on the wall painting fragment, which
      provides detailed information on the minerals constituting the paint. Elemental
      analysis data obtained through LIBS were compared with molecular and crystal
      structure information from Raman spectroscopy and XRD. Cross-sections from
      selected samples were also investigated by means of optical microscopy and
      scanning electron microscopy coupled to micro-probe analysis and X-ray mapping
      that enabled identification of several mineral components of the paint confirming
      the results of the XRD analysis. In parallel, replica wall paintings, created
      with known pigments and binding media for reference purposes, were examined with
      optical microscopy and stain tested for organic materials. The overall study
      shows that the LIBS and Raman techniques offer key advantages, such as instrument
      mobility and speed of data collection and interpretation that are particularly
      important when dealing with on-site investigations. Thus, they are capable of
      providing important compositional information in an effective manner that enables
      quick surveying of wall paintings and permit targeted sample selection for
      further analysis by advanced laboratory techniques.

PMID- 21845534
TI  - Obesity and ADHD: clinical and neurobiological implications.
AB  - Although quite overlooked, increasing evidence points to a significant
      association between attention-deficit/hyperactivity disorder (ADHD) and obesity.
      Here, we present an updated systematic review and a critical discussion of
      studies on the relationship between ADHD and obesity, with a particular emphasis
      on the possible behavioral, neurobiological, and genetics underlying mechanisms.
      Available empirically based studies indicate that the prevalence of ADHD in
      clinical samples of patients seeking treatment for their obesity is higher than
      that in the general population. Moreover, although still limited, current
      evidence shows that individuals with ADHD have higher-than-average body mass
      index z-scores and/or significantly higher obesity rates compared with subjects
      without ADHD. Three mechanisms underlying the association between ADHD and
      obesity have been proposed: (1) obesity and/or factors associated with it (such
      as sleep-disordered breathing and deficits in arousal/alertness) manifest as ADHD
      like symptoms; (2) ADHD and obesity share common genetics and neurobiological
      dysfunctions, involving the dopaminergic and, possibly, other systems (e.g.,
      brain-derived neurotropic factor, melanocortin-4-receptor); and (3) impulsivity
      and inattention of ADHD contribute to weight gain via dysregulated eating
      patterns. With regards to the possible clinical implications, we suggest that it
      is noteworthy to screen for ADHD in patients with obesity and to look for
      abnormal eating behaviors as possible contributing factors of obesity in patients
      with ADHD. If further studies confirm a causal relationship between ADHD and
      obesity, appropriate treatment of ADHD may improve eating patterns and, as a
      consequence, weight status of individuals with both obesity and ADHD.

PMID- 21845535
TI  - Mechanisms related to neuron injury and death in cerebral hypoxic ischaemia.
AB  - Cerebral hypoxic-ischaemic injury is involved in many central nervous system
      diseases. The mechanisms of neuron injury and death in cerebral hypoxic ischaemia
      remain unclear. There have been many theories on pathogenesis of neuron injury
      and death in cerebral hypoxic ischaemia, such as the toxicity of excitatory amino
      acid, NO, the production of oxygen free radicals, chondriosome injury, complement
      component, injury of immunological inflammation, matrix metalloproteinase,
      dopamine, Ca2+ overloading, cell apoptosis and so on. The aim of this review is
      to describe recent observations regarding the mechanisms of neuron injury and
      death in cerebral hypoxic ischaemia.

PMID- 21845536
TI  - Expression of mutated isocitrate dehydrogenase-1 in gliomas is associated with
      p53 and EGFR expression.
AB  - Gliomas are the most common primary brain tumours. Several independent studies
      have shown that isocitrate dehydrogenase 1 (IDH1) mutation in diffuse gliomas is
      associated with a more favourable patient outcome. The aim of this study was to
      evaluate the prognostic relevance of an antibody specifically detecting the R132H
      point mutation of IDH1 in tissue sections in a large series of human gliomas.
      Surgical specimens of 220 consecutive patients with infiltrative low and high
      grade gliomas were included in this retrospective study. In multivariate
      analysis, IDH expression did not reach significance (p = 0.122) in regard to
      prognosis, in contrast to WHO grade and age at time of surgery (p < 0.001, Cox
      regression). A significant correlation of p53 expression to mutated IDH1 and
      histological grading and an inverse correlation to truncated EGFR expression were
      observed (p < 0.001, Mann-Whitney test). In sum, our results indicate that
      IDHR132H mutation correlates significantly with p53 and inversely with EGFR
      mutations. Further studies should investigate whether these correlations reflect
      involvement of these three molecules in a common signalling pathway.

PMID- 21845530
TI  - Recombinant human Hsp70 protects against lipoteichoic acid-induced inflammation
      manifestations at the cellular and organismal levels.
AB  - It has been previously reported that pretreatment with exogenous heat shock
      protein 70 (Hsp70) is able to protect cells and animals from the deleterious
      effects of bacterial lipopolysaccharide (LPS) produced by Gram-negative bacteria.
      However, the effects of Hsp70 pretreatment on lipoteichoic acid (LTA) challenge
      resulted from Gram-positive bacteria infection have not been fully elucidated. In
      this study, we demonstrated that preconditioning with human recombinant Hsp70
      ameliorates various manifestations of systematic inflammation, including reactive
      oxygen species, TNFalpha, and CD11b/CD18 adhesion receptor expression induction
      observed in different myeloid cells after LTA addition. Therefore, exogenous
      Hsp70 may provide a mechanism for controlling excessive inflammatory responses
      after macrophage activation. Furthermore, in a rat model of LTA-induced sepsis,
      we demonstrated that prophylactic administration of exogenous human Hsp70
      significantly exacerbated numerous homeostatic and hemodynamic disturbances
      induced by LTA challenge and partially normalized the coagulation system and
      multiple biochemical blood parameters, including albumin and bilirubin
      concentrations, which were severely disturbed after LTA injections. Importantly,
      prophylactic intravenous injection of Hsp70 before LTA challenge significantly
      reduced mortality rates. Thus, exogenous mammalian Hsp70 may serve as a powerful
      cellular defense agent against the deleterious effects of bacterial pathogens,
      such as LTA and LPS. Taken together, our findings reveal novel functions of this
      protein and establish exogenous Hsp70 as a promising pharmacological agent for
      the prophylactic treatment of various types of sepsis.

PMID- 21845537
TI  - Analysis of the prognostic significance of selected morphological and
      immunohistochemical markers in ependymomas, with literature review.
AB  - AIM: Ependymal tumours are relatively uncommon primary neoplasms of the central
      nervous system. Histological criteria distinguishing ependymoma and anaplastic
      ependymoma are not clear-cut and other parameters are required to allow more
      precise prognostication in these tumours. We analysed the histological and
      immunohistochemical features of these tumours (Ki-67, cyclin D1, EGFR, hTERT,
      Olig2) and correlated them with the clinical outcome. MATERIAL AND METHODS: We
      analysed 39 patients with grade II ependymoma (30) and anaplastic ependymoma (9).
      Twenty-eight tumours developed in children and the remaining 11 patients were
      adults with intracranial and intraspinal tumours. Eighteen patients died during
      the follow-up period. RESULTS AND CONCLUSIONS: Overall survival was reduced
      significantly for paediatric patients and patients with intracranial tumour. High
      grade tumours, increased mitotic index and increased cellularity had an
      unfavourable influence on survival. Other histological parameters such as nuclear
      atypia, necrosis and microvascular proliferation did not alter the survival rate.
      Increased Ki-67 and cyclin D1 indices correlated with worse prognosis.
      Furthermore, any level of cyclin D1 expression in WHO grade II ependymomas was
      strongly associated with higher risk of death. No correlation was identified
      between Olig2, EGFR and hTERT expression and the outcome of the patients.

PMID- 21845538
TI  - Radiation-induced lowered neurogenesis associated with shortened latency of
      inhibitory avoidance memory response.
AB  - The neural system is less sensitive to radiation than other late-responding
      organs and tissues such as the kidney and lung. The generation of new neurons in
      the adult mammalian brain has been documented in several works. Many studies show
      that adult hippocampal neurogenesis relates to hippocampal function, in several
      ways. In this study, we assessed the effect of single and fractionated cobalt
      radiation on neurogenesis in the dentate gyrus of the hippocampal formation. The
      irradiation time for delivering 2 Gy (for fractionated dose radiation) and 10 Gy
      (for single dose radiation) at maximum depth were respectively 1.98 min and 9.92
      min. To study the association with memory function we examined inhibitory
      avoidance memory using a step-through device. Brains were withdrawn and fixed,
      and then sections were stained with cresyl violet for neurons. We found that a 10
      Gy dose can induce lower neurogenesis in the dentate gyrus of the hippocampus (p
      < 0.05), in such a way that a fractionated dose (5 fractions of 2 Gy) is more
      effective than a single dose (one fraction of 10 Gy). Moreover, a fractionated
      dose could reduce step-through latency corresponding to damaged inhibitory
      avoidance memory (p < 0.05). Synergic action of an anaesthetic drug may be the
      cause of more reduction of neurogenesis in fractionated irradiated rats. There
      was no significant difference in latency of the inhibitory avoidance memory
      response between the single 10 Gy group and the sham group, while fractionated 10
      Gy could reduce latency. Different mechanisms of action in the two regimens of
      irradiation may be a reason.

PMID- 21845539
TI  - Astroglia disturbances during development of the central nervous system in
      fetuses with Down's syndrome.
AB  - Down's syndrome (DS), caused by aneuploidy of chromosome 21, is the most common
      chromosomal disorder. The most significant symptom of this disorder is mental
      retardation. Neuropathological changes found in the DS central nervous system
      (CNS), such as reduced number of neurons, alteration of synapses and synaptic
      spines or delayed myelination have been widely described. But there are only a
      few studies of DS-related glia disturbances. A growing number of astroglia new
      functions have recently been described. In our study we compared the number of
      astrocytes and radial glial cells in the frontal lobe of DS fetuses at 18-20
      weeks of gestation with that observed in age-matched controls. We found a
      substantially increased number of glial fibrillary acid protein (GFAP) positive
      cells in all age range samples of DS brains. We also noticed that in our study
      astrocytes in DS brains seem to be morphologically more mature than in controls
      of corresponding age. The same observation was made for radial glia. Taking into
      consideration the role played by astroglia during CNS development we believe that
      any change in their number, reduced or increased, can affect CNS development and
      lead to disturbances of both neurogenesis and synaptogenesis. A possible
      correlation between the increased number of astroglia and disturbances in CNS
      development is discussed.

PMID- 21845540
TI  - Research on alteration of neurons in vagal nuclei in medulla oblongata in
      newborns with respiratory distress.
AB  - Neuronal and axonal degenerative changes in motor vagal neurons (DMNV) and
      sensory vagal neurons (nTS) in the medulla oblongata in newborns were studied.
      Material was taken from the autopsies of newborns, live and dead newborns, in
      different gestational weeks (aborted, immature, premature and mature). 46 cases
      were studied. Material for research was taken from the medulla oblongata and lung
      tissue. Serial horizontal incisions were made in the medulla oblongata (+/- 4
      mm), commencing from the obex, where the DMNV and nTS vagal nuclei were explored.
      Fixed cuttings in buffered formalin (10%) were used for histochemical staining.
      Serial cuttings were done with a microtome (7 um). Pulmonary infections, being
      significant (p < 0.05), have an important place when studying respiratory
      distress (RD) in newborns. Morphological changes of nerve cells in DMNV and nTS
      nuclei in the medulla oblongata in newborns in different gestational weeks are
      more emphasized in matures in comparison to aborted and immature (p < 0.05).
      Depending on the lifetime of dead newborns, neuronal morphological changes in
      vagus nerve nuclei are significant (p < 0.05). Therefore, it can be concluded
      that pulmonary infections are often caused due to dramatic respiratory distress
      in newborns, while hypoxaemic changes in the population of vagus nerve neurons in
      respiratory distress are more emphasized in matures.

PMID- 21845541
TI  - Expression of 8-oxoguanine DNA glycosylase 1 (OGG1) and the level of p53 and TNF
      alphalpha proteins in peripheral lymphocytes of patients with Alzheimer's
      disease.
AB  - The aim of the study was to determine the extent of oxidative DNA damage (levels
      of 8-oxo2dG) and expression of OGG1 and p53 and TNF-alpha proteins in lymphocytes
      of Alzheimer's disease (AD) patients and a control group. The studies were
      conducted on 41 patients with AD, including 25 women and 16 men aged 34-84 years.
      The control group included 51 individuals, 20 women and 31 men aged 22-83 years.
      The level of 8-oxo2dG was determined using HPLC/EC/UV, and the level of OGG1 and
      p53 and TNF-alpha proteins was determined with the Western blot method. The
      results showed that both proteins participating in DNA repair (OGG1, p53) and the
      inflammatory protein TNF-alpha are involved in pathogenesis of neurodegenerative
      diseases. It also seems that a specific system for DNA repair (OGG1) may
      contribute to downregulation of the inflammatory factor (TNF-alpha) level,
      especially in the early stages of dementia. Moreover, the results showed that p53
      protein can fulfil its function in DNA damage repair only in early stages of
      dementia. It is possible that OGG1 and p53 and TNF-alpha proteins together or
      separately may be involved in pathogenesis of AD by repair of oxidative DNA
      damage and/or apoptosis.

PMID- 21845542
TI  - Presence of L-kynurenine aminotransferase III in retinal ganglion cells and
      corpora amylacea in the human retina and optic nerve.
AB  - BACKGROUND: Corpora amylacea (CAm) are a hallmark of aging and neurodegeneration.
      The presence of kynurenine aminotransferases I and II (KAT I and II) in CAm in
      the human retina and optic nerve has been already shown. The present study aimed
      to examine kynurenine aminotransferase III (KAT III) immunoreactivity in CAm in
      the human retina and optic nerve. MATERIAL AND METHODS: Polyclonal antibody
      against KAT III was used on sections of human eyes enucleated due to malignant
      uveal melanoma. PAS-stained sections of CAm were compared with KAT III stained
      ones. RESULTS: KAT III immunoreactivity was observed in CAm in the retina,
      prelaminar, laminar and retrolaminar region of the optic nerve with similar
      location to PAS-stained sections. The most intense staining was observed in the
      retrolaminar part of the optic nerve. KAT III immunoreactivity was also present
      in the cytoplasm of retinal ganglion cells. CONCLUSIONS: Expression of KAT III in
      CAm in the human retina and optic nerve indicates that this enzyme may be
      relevant in mechanisms of neurodegeneration leading to CAm formation.

PMID- 21845543
TI  - Interleukin 17 receptor in multiple sclerosis patients treated with interferon
      beta-1a.
AB  - Interleukin 17 (IL-17) and its receptor IL-17R1 produced by T-helper cells named
      Th17 are involved in the pathology of autoimmune diseases. In contrast to the at
      least partially explained role of IL-17 in pathology of multiple sclerosis, the
      significance of IL-17R in MS is unclear. Therefore we have studied the expression
      of IL-17R in the stable phase of multiple sclerosis treated by interferon beta
      1a. The studied material consisted of 20 MS patients with relapsing-remitting
      form of the disease, and fulfilling the diagnostic McDonald et al. criteria. The
      patients were treated subcutaneously every second day with 30 mg of interferon
      beta -1a (Betaferon). The interleukin 17 receptor level was measured by the ELISA
      immunoassay test using RayBio human IL-17R ELISA kit. After three months of
      therapy with interferon beta -1a the level of IL-17R was significantly higher
      than that established at the starting point. The level of IL-17R after 6 months
      of therapy was insignificantly higher than established in the previous study
      group (3 months of therapy). While it remains difficult to pinpoint the exact
      significance of upregulation of IL-17R in the early period of therapy, the
      present findings should be taken into account when considering the
      pharmacodynamics of interferon action in MS in view of the opinions on the
      crucial role of IL-17 in pathology of MS and suggestions that it may constitute a
      drug target in autoimmunological diseases.

PMID- 21845544
TI  - Rosiglitazone protects the dorsal root ganglion cells and sciatic nerve after
      crush in rat.
AB  - The aim of this study was to investigate the histological changes in the dorsal
      root ganglion (DRG) and the sciatic nerve in rats after sciatic nerve crush (SNC)
      and treatment with rosiglitazone. The rats were divided into four groups, each
      including seven animals, and underwent the following intervention. Group I:
      control animals which received carboxy methyl cellulose (0.5 w/v, p.o.). Group
      II: sham operated animals whose skin of the posterior thigh was opened, closed
      and the animals received the vehicle (carboxy methyl cellulose). Group III: SNC
      animals; the animals received the vehicle. Group IV: SNC with rosiglitazone (5
      mg/kg body weight/day) dissolved in the vehicle. On the 28th day the fifth lumbar
      DRG and sciatic nerve were removed. Volume of the dorsal root ganglion, total
      volume and number of cells (A and B cells) of DRG, total surface area of the
      cells, and total number, diameter and cross-sectional area of the myelinated
      nerve fibres were estimated using stereological techniques. No change was
      observed in volume of the DRG, but all of the other parameters were decreased
      after nerve crush. In SNC+ rosiglitazone treated rats, the parameters decreased
      but to a lesser extent in comparison with the non-treated SNC group. It can be
      concluded that rosiglitazone has a protective effect on the DRG cells and sciatic
      nerve after crush in rats.

PMID- 21845546
TI  - [Interview - muscular dystrophies - worldwide search for patients].

PMID- 21845548
TI  - [Not Available].

PMID- 21845547
TI  - [What are the young academics in O und U doing?].

PMID- 21845549
TI  - [Not Available].

PMID- 21845550
TI  - [Not Available].

PMID- 21845551
TI  - [Not Available].

PMID- 21845552
TI  - [Childhood trauma and health care: to know is to recognize and to acknowledge].

PMID- 21845553
TI  - [The aftermath of the reduction in inpatient care and treatment; a retrospective
      study that considers the extent to which a group of chronic psychiatric patients
      made use of the Amsterdam mental health services].
AB  - BACKGROUND: The move towards less hospital care and more community care for
      psychiatric patients began in the eighties. Chronic patients possibly have not
      really benefited from the new procedures. AIM: To find out whether chronic
      psychiatric patients in Amsterdam were receiving adequate care and made good use
      of the available psychiatric services. METHOD: We amalgamated the registration
      details of three mental health care institutions in Amsterdam over the period 1-1
      2000 to 1-1-2005. RESULTS: In 2005 4576 patients met the criteria for chronic
      mental illness. In five years, the number of patients in mental health care had
      risen by 50%. Most of these patients had received care via specialised
      programmes. 38% of chronic patients had no access to specialised programmes, many
      of which had waiting lists. Only 6.5% of chronic patients received long-term
      inpatient care. Not many long-term psychiatric patients used the acute
      psychiatric services. Each year only 10% of long-term psychiatric patients were
      admitted to a psychiatric hospital. If admitted, they spent a much longer time in
      hospital. The average number of days spent in hospital rose from 86 in 2000 to
      131 in 2004. Crisis contacts increased in line with the increase in the numbers
      of chronic patients in care, but these crisis contacts were registered mainly
      with the patient treatment team and not with the municipal acute psychiatric
      service. CONCLUSION: Only a small proportion of long-term psychiatric patients
      make use of the acute psychiatric services.

PMID- 21845554
TI  - [Medical students and their attitude to psychiatry].
AB  - BACKGROUND: The attitudes of medical students to psychiatry are important for the
      future care of patients with psychiatric (co)morbidity. Up till now the attitude
      of medical students to psychiatry has not been investigated in the Netherlands
      and the Dutch-speaking part of Belgium. AIM: To measure the attitude of third
      year medical students towards psychiatry by means of the ATP-30. This is a
      validated instrument, used internationally. To determine the extent to which
      medical students' attitudes were influenced by the psychiatry curriculum and by
      some sociodemographic determinants and which aspects of a career - according to
      earlier Dutch research - made students decide to opt for a particular specialism.
      METHOD: Our research was of the prospective cohort type; without controls. The
      design was a pre- and post design. RESULTS: Attitudes to psychiatry were
      generally positive (n = 262, ATP score: 106.1, sd 10.9, ATP score <= 90 was
      regarded as negative) and improved after students received instruction in
      psychiatry. Men were less positive than women. Students who previously had
      positive experiences with the psychiatric services had higher scores. Foreign
      students, mainly from non-Western countries, had lower scores. After these
      foreign students had completed their studies in the Netherlands, there was no
      longer any significant difference between the scores of the two groups.
      CONCLUSION: Attitudes to psychiatry are positive within our cohort. Tuition has a
      positive effect on students' attitudes. The less positive score of the foreign
      students at the start of their course is probably due to the fact that they were
      not familiar with psychiatry and psychiatric services.

PMID- 21845555
TI  - [Body-directed techniques on psychomotor therapy for people with schizophrenia: a
      review of the literature].
AB  - BACKGROUND: Patients with schizophrenia frequently undergo a disturbance of body
      experience. This can occur during an acute psychotic phase or during a period of
      remission. AIM: To investigate the scientific evidence of the effects of
      introducing body-directed techniques into psychomotor therapy for patients with
      schizophrenia. METHOD: PubMed, PEDro, CINAHL, psycINFO and SPORTDiscus were
      searched form 1 January, 2000, tot 1 January 2011, for reports of randomised
      controlled trials, controlled clinical trials and for studies wit a different
      design. The Tijdschrift voor Psychiatrie (the Dutch Journal of Psychiatry), the
      Tijdschrift voor Vaktherapie (The Journal for Special therapies) and Actuele
      Themata (Actual Themes) in psychomotor therapy were also screened. The quality of
      the methodology was assessed with the help of a checklist. Evidence for the
      efficacy of the interventions was summarised on the basis of a best-evidence
      synthesis. RESULT: Eleven studies satisfied our inclusion and exclusion criteria.
      There was a strong evidence for the reduction of psychiatric symptoms after yoga
      and reduced feelings of anxiety and stress after progressive muscle relaxation.
      There is limited evidence for yoga in reducing feelings of anxiety and stress and
      for body-directed group techniques in reducing negative symptoms. Qualitative
      research reported that mindfulness - and massage-techniques were able to
      considerably reduce feelings of stress. There is no evidence for the beneficial
      effects of dancing techniques. CONCLUSION: A body-directed approach can be
      effective an deserves to be included in the multidisciplinary treatment of
      schizophrenia.

PMID- 21845556
TI  - [Assisted suicide in psychiatry; current situation and notes on a recent case].
AB  - BACKGROUND: The Dutch legal system grants psychiatric patients the right to
      assisted suicide but imposes strict conditions. The matter, however, remains
      controversial. Many psychiatrists are reluctant to become involved in assisted
      suicide because they are not familiar with the procedure that has to be followed,
      nor are they clear about the precise meaning of 'acting responsibly'. AIM: To
      provide an overview of the procedure to be followed and of the criteria to be met
      when a psychiatrist is wondering whether to grant a patient's request for
      assistance with suicide. METHOD: We analyse the law, jurisprudence and medical
      ethics and the special problems that arise in the case of psychiatric patients.
      RESULTS: We describe the developments in law and psychiatric practice which have
      led to greater recognition of the autonomy of the patient. The final decision
      depends on an assessment of the patient's competence and his ability to
      articulate his request clearly and on the hopelessness engendered by unbearable
      suffering. CONCLUSION: In the future there may be an increase in the number of
      cases of assisted suicide in psychiatry now that procedures and criteria have
      been established which are in accordance with the Dutch legal system.

PMID- 21845557
TI  - [The 'good death' in the Flemish psychiatry].

PMID- 21845558
TI  - [Peri-orbital oedema and therapy-resistant hypertension: unusual side-effects of
      clozapine].
AB  - A 49-year-old male, known to have been suffering from paranoid schizophrenia for
      10 years, was treated twice with clozapine. Although the clozapine alleviated his
      psychosis, the patient developed peri-orbital oedema repeatedly. As a result he
      requested a switch to a different antipsychotic. Also, while the patient was on
      clozapine, it proved difficult to regulate his hypertension. A possible
      explanation for these two side-effects is that clozapine blocks the renal
      dopamine D4 receptor, preventing it from performing its normal natriuretic and
      diuretic function. In view of the high but largely unnoticed incidence of
      hypertension in patients on clozapine (4%), we advise that such patients should
      receive structured somatic screening in a clinical setting.

PMID- 21845559
TI  - [Vitamin D deficiency and psychiatric patients].
AB  - A poor diet and a lack of exposure to sunlight are common in patients with a
      psychiatric disorder. Both factors play a major role in the development of
      vitamin D deficiency. The prevalence of vitamin D deficiency might be higher in
      psychiatric patients due to the symptoms of the psychiatric disorder itself. By
      way of illustration, we focus on two patients who were diagnosed with a severe
      vitamin D deficiency during admission to a psychiatric clinic. In addition, we
      give advice regarding the diagnosis and treatment of vitamin D deficiency.

PMID- 21845560
TI  - [Reaction on '"Histrionic personality disorder with regression and conversion": a
      meningioma'].

PMID- 21845561
TI  - Analysis of the mortality probability of preoperative MRI features in malignant
      astrocytomas.
AB  - AIM: The aim of the present study is to analyze the effects of the MRI features
      on the recurrence time and prognosis, and to emphasize the analyses of mortality
      risks in malignant astrocytomas. MATERIAL AND METHODS: The effects of
      preoperative MRI features on prognosis were studied for follow-up period of 45
      months, from November 1999 to August 2003, on a total of 79 patients' 41 cases of
      total resection and 38 cases of subtotal resection diagnosed to have malignant
      astrocytoma subsequent to craniotomy. RESULTS: The cases of gross total resection
      had 2.2 times as high survival rate as those in the subtotal resection group (p <
      0.01). The comparison of the cases in the groups in relation to their ages
      revealed that mortality rate rose 4.35 times (p < 0.01) in the age group of 60
      years and above, and 2.1 times in the age group of 45-59 years. When cases
      without necrosis were compared with the group containing necrosis of grade 1, 2,
      3, it was observed that the probability of mortality increased 3.84 (p < 0.01),
      4.15 times (p < 0.01) in the case of necrosis of grade 2 and 3, respectively by
      means of Cox regression model. CONCLUSION: Necrosis in preoperative MRI of
      malignant astrocytomas seems to be an important clinical marker of the prognosis.

PMID- 21845562
TI  - Natural course of the arteriovenous malformations of the brain initially
      presented by hemorrhage: analysis of a clinical series of 39 patients.
AB  - AIM: AVM because of outstanding tendency toward bleeding, even though 20 times
      more rare then aneurysm on the blood vessels of the brain and her own specific
      anatomical structure even today represents big neurosurgical challenge. MATERIAL
      AND METHODS: Series which is shown here consists of 39 patients which were
      hospitalized in the institute for neurosurgery of the Clinical Center of Serbia
      in the period between 1995 and 2004. This group was exposed to symptomatic
      therapy or it was estimated that surgery, embolization and radio surgery.
      RESULTS: Combined type of venous drainage brings a high risk (p < 0.001) from
      repeated bleeding. Combined artery bringing from different flows (p < 0.05)
      contributes to genesis of 'steal phenomenon', in combination with deep venous
      drainage it presents predisposing anatomical characteristics for repeated
      bleeding (p < 0.001) according to our results should present AVM with dimensions
      2.5 to 5 cm localized in eloquent zone of big brain with combined type of venous
      drainage and cobined artery bringing from vertebro-basilar flow and carotid flow.
      CONCLUSION: Perception of natural course of AVM point to certainly more benign
      pathology in regard to other vascular malformations. Specific anatomical
      structure requires planning of treatment from case to case, most often
      combination of embolization, radio surgery and surgical treatment.

PMID- 21845563
TI  - Use of tape measure in people with or without back pain in assessment of
      reposition error.
AB  - AIM: Examining lumbar repositioning error (RE) using a tape measure in
      nonspecific low back pain (NLBP) and control groups and determining whether RE is
      different in subjects with nonspecific back pain than in controlled subjects.
      MATERIAL AND METHODS: The study was totally applied to 36 subjects of whom 18
      were healthy subjects and 18 were NLBP patients. The ability of the subjects to
      take the targeted positions was assessed. In subjects with NLBP the evaluation of
      the pain was assessed by using Visual Analog Scale (VAS), and disability
      measurement was made using Oswestry Disability Index (ODI). RESULTS: RE was found
      in all the measurements except for lumbar flexion with eyes open(p=0.15) in
      control group (p < 0.05). There were RE for all the measurements in NLBP grpup (p
      < 0.05). When RE of two groups compared only lumbar flexion with eyes open
      measurement (p = 0.04) in NLBP group was higher then control group. CONCLUSION:
      As a result of our study, it has been seen that RE measurement of the lumbar
      spine with tape measure, which is cheap and clinically practical, is a reliable
      method, and can be used in the assessment of NLBP patients and in the
      determination of the rehabilitation program.

PMID- 21845564
TI  - Does disc space height of fused segment affect adjacent degeneration in ALIF? A
      finite element study.
AB  - AIM: The restoration of disc space height of fused segment is essential in
      anterior lumbar interbody fusion, while the disc space height in many cases
      decreased postoperatively, which may adversely aggravate the adjacent segmental
      degeneration. However, no literature available focused on the issue. MATERIAL AND
      METHODS: A normal healthy finite element model of L3-5 and four anterior lumbar
      interbody fusion models with different disc space height of fused segment were
      developed. 800 N compressive loading plus 10 Nm moments simulating flexion,
      extension, lateral bending and axial rotation were imposed on L3 superior
      endplate. The intradiscal pressure, the intersegmental rotation, the tresca
      stress and contact force of facet joints in L3-4 were investigated. RESULTS:
      Anterior lumbar interbody fusion with severely decreased disc space height
      presented with the highest values of the four parameters, and the normal healthy
      model presented with the lowest values except, under extension, the contact force
      of facet joints in normal healthy model is higher than that in normal anterior
      lumbar interbody fusion model. With disc space height decrease, the values of
      parameters in each anterior lumbar interbody fusion model increase gradually.
      CONCLUSION: Anterior lumbar interbody fusion with decreased disc space height
      aggravate the adjacent segmental degeneration more adversely.

PMID- 21845565
TI  - The surgical treatment of plagiocephaly.
AB  - AIM: Anterior plagiocephaly usually occurs with premature synostosis of the
      ipsilateral half of the coronal suture. The forehead is flattened on the affected
      side, with a backward and upward displacement of the affected orbit. The bulging
      of the calvaria may occur in the contralateral parietal area. MATERIAL AND
      METHODS: This article presents the surgical techniques used over 7 years to treat
      plagiocephalic children. Eleven patients with unilateral coronal synostosis
      treated during 2003-2010 were analyzed retrospectively. The study included
      reviews of pre and postoperative computed tomography scans, operative techniques,
      clinical outcomes and complications. Unilateral orbital advancement with "tongue
      in groove" was performed in 5, and bilateral orbital advancement in 6 cases. Pre
      and postoperative anthropometric measurements were used to document the amount of
      advancement of the elevated and recessed orbita, and the amount of withdrawal of
      the contralateral side. RESULTS: The mean age of the patients at time of surgery
      was 11 months. The preoperative values of the orbital height and retrusion were
      0.68 cm and 1.87 cm, respectively. They were recorded as -0.1cm and 0,63 cm,
      postoperatively. Mean follow-up was 36 months, neither neurological sequelae nor
      other significant complications were encountered. CONCLUSION: The surgical
      corrections have resulted in significant improvements in skull shape and high
      patient/parent satisfaction.

PMID- 21845566
TI  - Surgical timing of the subependymal giant cell astrocytoma (SEGA) with the
      patients of tuberous sclerosis complex.
AB  - AIM: Tuberous sclerosis complex has shown a wide variety of clinical, pathologic
      and radiologic manifestations. Many tumor types are found in tuberous sclerosis,
      which includes subependimal giant cell astrositoma. The aim of this study is to
      focus on surgical timing of the tumor. MATERIAL AND METHODS: This study included
      37 children with tuberous sclerosis presenting to Erciyes Univercity Medical
      School, whose hospital record were retrospectively evaluated between 1995 and
      2010. Of the 5 patients had diagnosed with the subependymal giant cell
      astrocytoma and three patients were opereted on. RESULTS: In the 27 of the
      patients had subependimal nodules (73%), cortical tubers were in the 19 patients
      (51,4%), giant cell astrositoma (SEGA) were in the 5 patients (13,5%). Mental
      retardation in different level was detected in the 18 patients (48.6%). The other
      clinical findings of the patients were angiomyolipomas (37.8%), hypomelanotic
      macules (91.9%), Convulsion (54.1%), adenoma sebaceum (32.4%) , West syndrome
      (16.22%), shagreeen patch (16.2%), intracardiac tumor (37.8%), subungual fibroma
      (2.7%), fibroadenom in the neck (2.7%). CONCLUSION: A multidisciplinary approach
      is essential for an early, accurate diagnosis and proper management of affected
      individuals. The early surgical menagement for subependimal giant cell
      astrocytoma are recommended, and also periodic monitoring even for asymptomatic
      patients with subependymal nodules.

PMID- 21845567
TI  - Memory difficulties of adult patients with shunted hydrocephalus: a clinical
      study.
AB  - AIM: The purpose of this prospective study was to describe memory problems of
      adult patients with hydrocephalus. MATERIAL AND METHODS: The research group
      consisted of healthy adults (control group) and hydrocephlic adults
      (hydrocephalus group). The hydrocephalus group (n: 19) had no clinical signs or
      symptoms of increased intracerebral pressure. The control group (n:20) was chosen
      from healthy adults. Both groups were evaluated by an experienced neuro
      psychologist blinded to the groups. The examiner performed a battery of three
      different neuropsychological tests (Raven Standart Progressive Matrices, RSPM;
      Rey-Osterrieth Complex Figure Test, RCFT; and Rey Auditory-Verbal Learning Test,
      AVLT) to all groups. RESULTS: Almost all subtest scores of the AVLT and RCFT
      remained significant after the RSPM scores were controlled. Almost all
      neuropsychological test results of the hydrocephalus group were significantly
      worse than control group. CONCLUSION: This prospective study showed that adult
      patients with hydrocephalus have serious problems in memory function which might
      be directly caused by the hydrocephalus.

PMID- 21845568
TI  - A new endoscopic surgical classification and invasion criteria for pituitary
      adenomas involving the cavernous sinus.
AB  - AIM: There are two major problems for the pituitary adenomas invading the
      Cavernous Sinus (CS); differentiation of extension and invasion and inability to
      demonstrate the medial wall via preoperative imaging methods. Two important
      corridors are defined in endoscopic cavernous sinus approaches; the lateral and
      medial corridor. MATERIAL AND METHODS: A retrospective analysis was performed in
      400 endoscopic transphenoidal approaches and 360 pituitary adenomas underwent
      endoscopic transphenoidal surgery in our department between September 1997 and
      December 2010. 48 patients affected by the tumours involving the cavernous sinus
      were included in this study. RESULTS: We performed an intraoperative evaluation
      of cavernous sinus invasion considering visualization of the medial wall defect,
      intracavernous ICA segments, minor tumour extensions through small focal pit
      holes of the medial wall of CS or confirming carotid segments of CS by micro
      doppler. Cavernous sinus involvement was classified into three types according to
      the medial and lateral corridor extension of the tumor as 25 isolated medial
      corridor involvement (Type I), 5 isolated lateral corridor involvement (Type II)
      and 18 total involvement (Type III). CONCLUSION: Our classification depends on
      fully surgical endoscopic approach supported by neuroimaging techniques and
      anatomical studies and shows a good predictive value for all cavernous sinus
      involvement.

PMID- 21845569
TI  - The effects of analgesia-sedation on the immune system before and after cerebral
      digital subtraction angiography.
AB  - AIM: Cerebral digital subtraction angiography (DSA) is an invasive procedure and
      may cause inflammatory responses in the body. This study aims to provide cytokine
      and lymphocyte profile in a population of patients underwent cerebral DSA.
      MATERIAL AND METHODS: Forty-one male patients who admitted for cerebral DSA were
      included in this study. Patients were divided into two groups: Group I (n = 7)
      included patients who did not receive analgesia-sedation and group II (n = 34)
      received analgesia-sedation before procedure. For the molecules, a venous blood
      samples from every patient was collected before and after cerebral DSA. RESULTS:
      Cytokine levels in group I showed a trend to increase in the majority of the
      molecules after the procedure except IL-1beta. In group II, cytokines showed
      variable trend. When comparing the two groups regarding cytokine levels after
      cerebral DSA, IL-1beta, IL-10, IL-12, and IFN-gamma levels increased
      significantly in group II. Comparing the two groups with respect to lymphocytes
      after cerebral DSA showed that CD56 levels were significantly higher in group II
      and other parameters did not show significant differences. CONCLUSION: It can be
      possible that delimitation of the action(s) of the cytokines affecting the
      secretion or activation of CD56 (natural killer) may avoid complications of
      inflammation after invasive procedures.

PMID- 21845570
TI  - Computed tomography findings in cerebral hydatid disease.
AB  - AIM: To describe imaging findings of cerebral hydatid cysts on computed
      tomography of brain. MATERIAL AND METHODS: We retrospectively reviewed CT scans
      of brain in 5 patients with pathologically confirmed hydatid cysts in cerebral
      hemispheres. The patients were scanned either on a spiral (single slice) CT or on
      multidetector-row CT before and after intravenous injection of iodinated contrast
      material. RESULTS: All the patients were children aged 8 to 13 years with 3 boys
      and 2 girls. Features of raised intracranial tension were present in all the
      cases at presentation. CT findings of a large intracerebral cystic lesion with
      significant mass effect and without any calcification or enhancement were common
      in all 5 cases. Perilesional edema was present in 1 case. Cerebral hydatid was
      seen as either a homogenous fluid attenuation unilocular cyst (3 cases) or a
      unilocular cyst with few peripheral daughter cysts (1 case) or cyst filled by
      multiple daughter cysts inside (1 case). All the cases were operated and cyst was
      removed completely after craniotomy. CONCLUSION: Accurate preoperative diagnosis
      of cerebral hydatid by CT followed by surgery with care to avoid cyst rupture can
      result in favorable outcome.

PMID- 21845571
TI  - Neuroprotective effect of memantine on hippocampal neurons in infantile rat
      hydrocephalus.
AB  - AIM: The effect of memantine administration on hippocampal neurons of the
      infantile rats with kaolin induced hydrocephalus was investigated. MATERIAL AND
      METHODS: Hydrocephalus was induced by injecting kaolin into the cisterna magna of
      3-weeks old Sprague-Dawley rat pups. One group received a single daily dose of
      20mg/kg memantine i.p. following hydrocephalus induction for a period of two
      weeks. By the end of the two-week period, animals were radiologically evaluated
      by magnetic resonance imaging and then sacrificed to get their cerebrums removed.
      Both immunohistochemical analysis of nitric oxide synthase activity and
      quantification of spared neurons in CA1, CA2 and CA3 regions of hippocampus were
      performed. RESULTS: In hydrocephalus-induced rats considerable neuronal loss
      associated with significantly increased nitric oxide synthase immunoreactivity
      were determined in all hippocampal regions. However, memantine treated rats
      showed significantly higher number of spared neuron counts and reduced nitric
      oxide synthase immunoreactivity in CA1 and CA2 regions compared with the non
      treated rats. CONCLUSION: The findings of the study show that hippocampal neurons
      may constitute important targets for injury secondary to hydrocephalic process in
      experimental infantile hydrocephalus. Early anti-excitotoxic treatment with
      memantine seems to have a neuroprotective effect especially in the CA1 and CA2
      subunits of the hippocampus.

PMID- 21845572
TI  - Ultrastructural changes in the Liliequist membrane in the hydrocephalic process
      and its implications for the endoscopic third ventriculostomy procedure.
AB  - AIM: Fenestration of Liliequist membrane (LM) during endoscopic third
      ventriculostomy (ETV) is extremely important for the success of the procedure. It
      is noteworthy that LM usually shows a tough and dense stucture in long-standing
      hydrocephalus cases different from its usual arachnoidal membrane-like structure
      observed in new-onset hydrocephalus cases. The structural variation of LM in
      different hydrocephalic states was investigated histologically in this study.
      MATERIAL AND METHODS: Specimens of LM obtained during endoscopic fenestration in
      11 cases were examined under transmission-electron-microscopy. Six cases had long
      standing hydrocephalus and five had new-onset triventricular hydrocephalus. None
      of the cases had a history of infection or hemorrhage. RESULTS: In cases with
      long-standing hydrocephalus, ultrastructural examinations revealed the existence
      of regular and dense bundles of type-I collagen among the fibroblast-like cells,
      which were closely connected by dense desmosomes and gap-junctions. In cases with
      new-onset hydrocephalus, it was observed that the cells usually had long
      cytoplasmic extentions and were connected with loose desmosomes. Sparse type-I
      collagen bundles were observed rarely among the cells. CONCLUSION: These results
      suggest that the structure of LM may change with the duration of the
      hydrocephalic process. This may help explain the tough and dense LM stucture
      observed during the ETV procedure in cases with long-standing-hydrocephalus.

PMID- 21845573
TI  - Neuroprotective effect of ACE inhibitors in glutamate - induced neurotoxicity:
      rat neuron culture study.
AB  - AIM: Glutamate is known to be neurotoxic at concentrations of 10-6M and 10-7M.
      Angiotensin converting enzyme (ACE) inhibitors can be assumed to be
      neuroprotective as they open the mitochondrial adenosine triphosphate-sensitive
      potassium channels by inhibiting the degradation of bradykinin. In this study, we
      investigated whether the ACE inhibitors captopril, ramipril and perindopril have
      protective effects in glutamate-induced neurotoxicity in newborn rat cerebral
      cortex cell cultures. MATERIAL AND METHODS: Viability tests were performed among
      ACE inhibitors by constituting groups of control and 10-7M and 10-6M glutamate
      doses in newborn rat cortex cultures. RESULTS: While the mean viable cell number
      was 0.47+/-0.06 in the control group, it was 0.37+/-0.03 in the group exposed to
      10-7M glutamate (p < 0.05) and 0.37+/-0.01 in the group exposed to 10-6M
      glutamate (p < 0.05). Captopril was used at a dose of 10 MUM, perindopril was
      used at a dose of 1 MUM, and ramipril was used at a dose of 30 MUM against 10-7M
      and 10-6M glutamate. Ramipril and perindopril reversed the toxicity against 10-6M
      glutamate (p < 0.05). The neuroprotective properties of captopril, perindopril
      and ramipril were not found to be statistically significant against 10-7M
      glutamate at the doses mentioned above. CONCLUSION: Data obtained from this study
      indicate that ramipril and perindopril can prevent 10-6M glutamate-induced
      neurotoxicity.

PMID- 21845574
TI  - Subarachnoid, subdural and interdural spaces at the clival region: an anatomical
      study.
AB  - AIM: We aimed to show the significance of the anterior pontine membrane as a
      determining structure between the subdural and subarachnoid space in the clival
      region. MATERIAL AND METHODS: Five adult cadaver heads and five cerebral
      hemispheres were used. The skull vault and hemipheres were removed by sectioning
      through the pontomesencephalic junction. Five other heads hemispheres were
      removed but the arachnoid membrane was protected and the cerebral side of the
      clival dura mater was dissected. In another specimen, the dural porus of the
      abducens nerve was sectioned for histological evaluation. Three cases of hematoma
      at the clivus were presented to support our findings. RESULTS: The anterior
      pontine membrane is the arachnoid membrane forming the anterior wall of the
      prepontine cistern with its lateral extension at the skull base. This membrane
      forms the subdural and subarachnoid spaces by forming a barrier between the
      clival dura mater and neurovascular structures of the brainstem. There were rigid
      fibrous trabeculations between both cerebral and periosteal dural layers forming
      the basilar plexus as the interdural space in the clivus. CONCLUSION: The
      anterior pontine membrane separates the subdural and subarachnoid spaces at the
      clival region. The hematomas of the clival region require to be evaluated with
      consideration given to the existance of the subdural space.

PMID- 21845575
TI  - A morphometric study of foramen ovale.
AB  - AIM: To note the morphological variations and morphometric details of foramina
      ovale in dry adult skulls of Indian origin. MATERIAL AND METHODS: 82 dry adult
      human skulls of unknown sex and of Indian origin were obtained and variations in
      appearance and number of foramen ovale were noted. The length and width of the
      foramina ovale of both sides were determined using digital Vernier calipers and
      area (A) was also calculated and analyzed. RESULTS: Out of 82 adult skulls, the
      values for the right side was 7.64 +/- 1.194 mm, 5.128 +/- 0.827 mm and 30.808 +/
      7.545 mm2 and for the left side the values was 7.561 +/- 1.123 mm, 5.244 +/-
      0.950 mm and 31.310 +/- 8.262 mm2 respectively, for the mean length, width and
      area of the foramen ovale. The shape of foramen was typically ovale in most of
      the skulls (56.70%) with some bony variations such as spine, tubercles etc.
      CONCLUSION: There was no statistically significant difference between the two
      sides in length, width and area of foramen ovale and there was a positive
      correlation between lengths and areas of both sides.

PMID- 21845576
TI  - Accessory transverse foramina in the cervical spine: incidence, embryological
      basis, morphology and surgical importance.
AB  - AIM: To study the incidence of accessory foramina transversaria in cervical spine
      and to analyze them morphologically with emphasize on their embryological and
      surgical importance. MATERIAL AND METHODS: The study included 363 human cervical
      vertebrae which were procured from the bone collections of the Department of
      Anatomy. The foramen transversarium was observed macroscopically on both sides of
      all the vertebras, the accessory foramina were noted. RESULTS: Out of 363
      specimens, only 6 (1.6%) vertebrae showed the accessory foramina. Among them 5
      (1.4%) vertebra had double foramina and only 1 (0.3%) vertebra showed three
      foramina. Only 1 (0.3%) vertebrae showed the foramen on both sides and the
      remaining 5 (1.4%) had unilateral foramina. Among the unilateral, 4 were present
      on the right side and only 1 was on the left side. No vertebrae showed the
      absence of foramen transversarium. CONCLUSION: The present study observed the
      accessory foramina transversarium in 1.6% of cases. The unilateral presence was
      more common than the bilateral. The surgical anatomy of these variations is
      important for the neurosurgeons and radiologists for interpreting the computed
      tomogram and magnetic resonance image scans. Their morphological knowledge is
      clinically important since the course of the vertebral artery may be distorted in
      such situations.

PMID- 21845577
TI  - Anatomic variations of the median nerve in the carpal tunnel: a brief review of
      the literature.
AB  - Carpal tunnel syndrome (CTS) is a common focal peripheral neuropathy. Increased
      pressure in the carpal tunnel results in median nerve compression and impaired
      nerve perfusion, leading to discomfort and paresthesia in the affected hand.
      Surgical division of the transverse carpal ligament is preferred in severe cases
      of CTS and should be considered when conservative measures fail. A through
      knowledge of the normal and variant anatomy of the median nerve in the wrist is
      fundamental in avoiding complications during carpal tunnel release. This paper
      aims to briefly review the anatomic variations of the median nerve in the carpal
      tunnel and its implications in carpal tunnel surgery.

PMID- 21845578
TI  - Comparison of simultaneous shunting to delayed shunting in infants with
      myelomeningocele in terms of shunt infection rate.
AB  - AIM: Timing of shunt insertion in infants with myelomeningocele (MM) and
      hydrocephalus (HCP) has been debated. Many authors have suggested to perform the
      repair of MM and shunt insertion during same operation. However, there is also an
      opposite view. MATERIAL AND METHODS: We analyzed retrospectively 166 patients who
      underwent MM Sac repair to evaluate whether there are difference between these
      two methods in terms of shunt infection rate. RESULTS: In the same session, V-P
      (ventriculoperitoneal) shunt placement was performed onto 65 infants within the
      first 48 hours of postnatal and 36 infants were operated 48 hours after birth. In
      separate sessions, repair of MM were performed onto 29 infants within the first
      48 hours of postnatal and shunting was peformed 7 days after sac repair. 14
      infants were performed MM sac repair 48 hours after birth, then shunt was applied
      7 days after closure of MM. Shunt infection rate in concurrently operated groups
      was markedly high (12.3 % in early surgery, 33.3% in late surgery); in
      separatedly operated groups' shunt infection rate was lower (3.44% in early
      surgery, 14.29% in late surgery). CONCLUSION: We propose to perform V-P shunt
      placement and MM repair in separate sessions.

PMID- 21845579
TI  - Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.
AB  - Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors
      manifested as hyperthyroidism with goiter in the presence of elevated TSH. We
      present a case with pituitary adenoma secreting both TSH and growth hormone (GH)
      with the prominent clinical findings of hyperthyroidism but without clinical
      findings of acromegaly. Pituitary magnetic resonance imaging revealed a
      macroadenoma. Transsphenoidal surgery was performed twice. The
      immunohistochemical staining showed that tumor cells were strongly reactive to GH
      and relatively mildly reactive to TSH. Control pituitary imaging revealed a
      residual macroadenoma, and long acting octreotide treatment was administered.
      After two years of the treatment, tumor size remained the same while thyroid
      function tests and insulin-like growth factor 1 (IGF-I) values returned to normal
      ranges. In conclusion, we always recommend hormonal examinations for all patients
      who have pituitary adenoma without signs and symptoms of acromegaly.

PMID- 21845580
TI  - Spinal metastasis of occult lung carcinoma causing cauda equine syndrome with
      lumbar spinal stenosis.
AB  - AIM: Cancers that metastasize to the cauda equina are uncommon. Only seventeen
      cases were reported. Those from pulmonary squamous cell carcinoma was never been
      published to our knowledge. MATERIAL AND METHODS: A 79-year-old male patient
      presented with low back pain since 1 year and severe sacral pain irradiating to
      the left leg, paraparesis, urinary dysfunction and leg weakness since one week.
      RESULTS: Preoperative magnetic resonance images of the lumbar spine showed an
      intradural spinal mass in L2-3 with infiltration of the cauda equina; the lesion
      measured 13 mm craniocaudally and 11 mm anteroposteriorly, and thus occupied the
      majority of the intrathecal space at that level. The magnetic resonance images,
      surgical treatment, and related pathophysiology are reviewed. CONCLUSION: The
      majority of cauda equina tumors are primary tumors, and metastases are very rare.
      Especially old patients with intradural mass and rapidly progressive cauda equina
      syndrome should be evaluated for a primary malignancy to avoid an unnecessary
      spinal operation.

PMID- 21845581
TI  - Scissors in brain: an unusual presentation of tribal culture in India.
AB  - AIM: To observe the neurological complications arising from various tribal
      practices and their management. Penetrating head injuries comprise only a small
      number of total head injuries. A penetrating head injury by deliberate attempt to
      treat an ailment is almost unheard of. MATERIAL AND METHODS: We present here a
      case of penetrating head injury caused by stabbing a scissor in head by a local
      witch doctor in order to treat a psychiatric ailment. RESULTS: The patient was
      taken up for for surgery and managed accordingly. Relevant literature was
      reviewed regarding various foreign bodies in traumatic missile and non missile
      brain injuries and their surgical management.

PMID- 21845582
TI  - Elevated skull fractures in pediatric age group: report of two cases.
AB  - Elevated fractures of the skull, which are rarely reported in the literature, are
      always compound, have maximal neurological deficits at presentation and have been
      reported only in adults. We report two cases of elevated skull fractures in the
      pediatric age group, one of which was a simple elevated fracture and presented
      with delayed neurological deterioration. The etiologies were a fall in first case
      and an animal attack (bear maul) in the second case as reported for the first
      time. One of the cases presented with delayed onset of left focal hemispheric
      signs. The first case underwent debridement, duraplasty and reduction of fracture
      whereas in the second case the bone flap was not replaced immediately because of
      gross contamination. Both patients had an excellent outcome. Elevated skull
      fractures are not uncommon in the pediatric age group. Compound elevated skull
      fractures should be managed early as open depressed fractures. Reduction of a
      simple elevated fracture presenting with neurological deficits not explained by
      any other lesion can result in a good outcome.

PMID- 21845583
TI  - Bilateral pneumothorax during subdural-peritoneal shunting.
AB  - Pneumothorax is a very rare complication of ventriculoperitoneal shunting in
      children. We report a case of an iatrogenic bilateral tension pneumothorax during
      the placement of a subdural-peritoneal shunting. After the placement of
      peritoneal catheter, oxygen saturation of the patient quickly decreased,
      hypotension and bradycardia occurred. Intraoperative x-rays showed the
      pneumothorax. A thoracostomy tube was inserted and attached to an underwater
      seal. Vital signs improved in a short time period. The radiological improvement
      had been achieved in four days. Early diagnosis and prompt intervention are life
      saving for this complication. To avoid this complication, the tip of the shunt
      tunneler should be always palpable during the placement of the peritoneal
      catheter, especially in children's shunt surgery.

PMID- 21845584
TI  - Avulsion fracture of the anterior iliac crest after bone graft harvest: case
      report and review of techniques, risk factors and treatment.
AB  - The anterior iliac crest is the harvest site preferred by many surgeons because
      of the quantity and quality of bone obtainable and the simplicity of harvesting
      techniques. Avulsion fracture of the iliac crest following bone grafting is an
      extremely rare occurrence. We present a case report of avulsion fracture of the
      anterior iliac crest following bone graft harvesting for anterior cervical fusion
      in a 63-year-old man. Non-operative treatment was the method of our treatment in
      the patient. By means of the presented case, iliac crest bone grafting
      techniques, risk factors of avulsion fracture, and treatment options were
      reviewed.

PMID- 21845585
TI  - Cerebral tuberculoma mimicking high grade glial tumor.
AB  - Tuberculosis has been an important public health problem in both developing and
      develop nations. Tuberculosis of the central nervous system is rare. Tuberculosis
      meningitis and tuberculoma are the two most important manifestations of
      tuberculosis of the CNS. Intracranial tuberculomas may be solitary or multiple.
      Solitary tuberculomas may be indistinguishable from cranial abscess or primary
      brain tumor. It is necessary to rule out tuberculoma in patients with
      intracranial mass lesions. We present a case of tuberculoma mimicking a high
      grade glial tumor on magnetic resonance imaging and clinical presentation. A 30
      year-old woman presented with one-month history of epilepsy. Cranial magnetic
      resonance imaging showed a left occipital peripheral ring-enhanced lesion with
      central necrosis. There was a strong suspicion of glial tumor. The lesion was
      totally excised with left occipital craniotomy. Histological examination of mass
      revealed a tuberculoma. The patient was treated with antituberculous
      chemotherapy.

PMID- 21845586
TI  - Pseudoaneurysm of the superficial temporal artery following revision of a middle
      cerebral artery aneurysm clipping: case report and review of the literature.
AB  - Pseudoaneurysms of the superficial temporal artery are mostly traumatic in
      origin. Here, a case of a superficial temporal artery aneurysm that emerged
      following a recraniotomy is presented. A 59-year-old woman was admitted with
      subarachnoid hemorrhage. She underwent a pterional craniotomy and clipping of a
      saccular aneurysm of middle cerebral artery bifurcation. A control digital
      subtraction angiography on the 3rd postoperative day revealed partial filling of
      the aneurysm and a revision was performed. The second control digital subtraction
      angiography on the 4th postoperative day of the revision showed a pseudoaneurysm
      of the left superficial temporal artery. The pseudoaneurysm was excised
      successfully under local anesthesia. In conclusion, pseudoaneurysm of the
      superficial temporal artery should be considered among the early postoperative
      complications of the surgical procedures at the superficial temporal artery
      territory. Although some conservative approaches are used, excision of the
      aneurysm is recommended for treatment.

PMID- 21845587
TI  - Ulnar nerve entrapment in Guyon's canal due to recurrent carpal tunnel syndrome:
      case report.
AB  - Guyon's canal syndrome is a compression neuropathy of the ulnar nerve entrapment
      at the wrist. Compression of the ulnar nerve at the wrist by a ganglion, lipomas,
      diseases of the ulnar artery, fractures of the hamate and trauma are common
      etiologcal factors. Unlike Guyon's canal syndrome, carpal tunnel syndrome (CTS)
      is the most common nerve entrapment of the upper extremity. Although, open (OCTR)
      or endoscopic carpal tunnel release (ECTR) is highly effective in relieving pain,
      failure with carpal tunnel release is seldom seen. In this paper, we presented a
      patient with ulnar nerve entrapment associated with recurrent CTS and discussed
      the possible pathomechanism with a review of current literature.

PMID- 21845588
TI  - Myogenic and melanotic differentiated medulloblastoma: case report.
AB  - Medulloblastoma is the most common malignant tumor of childhood and usually
      arises from the cerebellar vermis. Several histological types of medulloblastoma
      have been described. Myogenic and melanotic differentiated medulloblastoma are
      seldom seen. We present a case diagnosed as myogenic medulloblastoma with focal
      areas of melanotic differentiation. A 4-year-old boy was admitted due to
      headache, nausea and vomiting for a month. MRI revealed a heterogeneous enhanced
      posterior fossa tumor rising from the fourth ventricle. He was operated and
      pathological examination of the specimen revealed myogenic medulloblastoma with
      myogenic and melanotic differentiation. According to our knowledge there are six
      cases reported in the literature so far. Oncogenic factors in medulloblastoma
      development are controversial. Presence of multiple differentiation patterns
      supports a pluripotent origin for these tumors.

PMID- 21845589
TI  - Polytetrafluoroethylene sponge syringosubarachnoid shunt.
AB  - Syringomyelia is condition in which a cyst or cavity forms inside the spinal
      cavity. Its management always remains a difficult. A variety of surgical
      techniques have been used in management of syringomyelia. Syringosubarachnoid
      shunt remains an effective method in management of syringomyelia. Shunt tube
      obstruction remains an important complication of shunt procedure. We describe a
      novel technique of use of polytetrafluoroethylene sponge shunt for
      syringosubarachnoid shunt in patient with large syrinx and Chiari 1 malformation.
      Polytetrafluoroethylene sponge is a non irritant material with multiple
      porosities that is less susceptible to blockages or kinking. It could provide a
      good alternative technique in syringosubarachnoid shunting.

PMID- 21845590
TI  - Posterolateral extrusion of C7-D1 intervertebral disc associated with intradiscal
      hematoma.
AB  - A case of an extruded cervical intervertebral disc at C7-D1 level with
      intradiscal hematoma in a 68-year-old male patient is presented. MR imaging
      showed a posterolateral extradural hemorrhagic lesion at C7-D1 level. It was
      suggestive of an epidural hematoma or a bleed within a neoplasm. A posterior
      approach was adopted and an extruded intervertebral disc with intradiscal
      hematoma was found and completely excised. Extruded cervical disc with
      intradiscal hematoma in a 68-year-old male has never been hitherto reported in
      the literature. The uniqueness of the case is the extruded cervical disc with
      hematoma within it presenting at an advanced age and unusual radiological
      features on MR imaging. The clinical presentation, radiological features and
      surgical management of this rare condition are discussed and the relevant
      literature is briefly reviewed.

PMID- 21845591
TI  - Synergistic associations of depression and apolipoprotein E genotype with
      incidence of dementia.
AB  - OBJECTIVES: A cohort study of Japanese-American men suggested interactive effects
      of depression and apolipoprotein E (APOE) e4 allele on risk of incident dementia.
      In another sample of East Asian origin, we sought to replicate the findings and
      to explore individual depressive symptoms where this interaction was most
      evident. METHODS: Of 625 Korean community elders without dementia at baseline,
      518 (83%) were followed over a 2.4-year period and were clinically assessed for
      incident dementia. Depression was identified by the Geriatric Mental State
      Schedule (GMS), and nine individual depressive symptoms relevant to DSM-IV major
      depressive episode criteria were extracted. APOE genotype was ascertained.
      Covariates included age, gender, education, and disability. RESULTS: There were
      synergistic interactions between depression and APOE e4 on incident dementia
      independent of covariates. This interaction was particularly strong for four
      depressive symptoms: depressed mood, worthlessness, concentration difficulty, and
      suicidal ideation. CONCLUSIONS: We were able to replicate the previous study,
      finding that, at least in East Asian origin populations, the APOE e4 allele is a
      stronger predictor of incident dementia in the presence of depressive syndrome,
      and particular depressive symptoms.

PMID- 21845593
TI  - Religious and spiritual beliefs in outpatients suffering from Parkinson Disease.
AB  - OBJECTIVE: Personality changes are known to occur in idiopathic Parkinson's
      Disease (PD). The aim of the study was to evaluate whether religious and
      spiritual beliefs in PD patients are different from age-matched controls. DESIGN:
      Eighty-three PD participants, 79 hypertensive individuals not affected by PD and
      88 healthy subjects participated to a cross-sectional study. The Royal Free
      Interview (RFI) was used to evaluate participants' beliefs. The Hospital Anxiety
      and Depression Scale (HADS) was applied to monitor emotional distress. RESULTS:
      There was no statistical evidence of a difference between PD participants and the
      two control groups, the only exception being observed between the left PD onset
      group and the controls, where the total RFI score was about 5 points higher (t
      test: p = 0.0273). RFI total score was uncorrelated with age, severity of illness
      and depression, but was strongly dependent on the type of beliefs. The percentage
      of PD participants suffering from anxiety and depression was high (right onset:
      54.8%; left onset: 68.6%), while only 15.2% of the hypertensive participants, and
      none of the healthy controls, had a HADS score above 10 points. Total RFI score
      was higher in women. CONCLUSION: PD participants maintain their Faith in spite of
      the disease severity. Differences are found between right and left onset of PD.
      The possible beneficial effect of religious coping is discussed.

PMID- 21845592
TI  - A brief dementia screener suitable for use by non-specialists in resource poor
      settings--the cross-cultural derivation and validation of the brief Community
      Screening Instrument for Dementia.
AB  - OBJECTIVE: Brief screening tools for dementia for use by non-specialists in
      primary care have yet to be validated in non-western settings where cultural
      factors and limited education may complicate the task. We aimed to derive a brief
      version of cognitive and informant scales from the Community Screening Instrument
      for Dementia (CSI-D) and to carry out initial assessments of their likely
      validity. METHODS: We applied Mokken analysis to CSI-D cognitive and informant
      scale data from 15 022 participants in representative population-based surveys in
      Latin America, India and China, to identify a subset of items from each that
      conformed optimally to item response theory scaling principles. The validity
      coefficients of the resulting brief scales (area under ROC curve, optimal
      cutpoint, sensitivity, specificity and Youden's index) were estimated from data
      collected in a previous cross-cultural validation of the full CSI-D. RESULTS:
      Seven cognitive items (Loevinger H coefficient 0.64) and six informant items
      (Loevinger H coefficient 0.69) were selected with excellent hierarchical scaling
      properties. For the brief cognitive scale, AUROC varied between 0.88 and 0.97,
      for the brief informant scale between 0.92 and 1.00, and for the combined
      algorithm between 0.94 and 1.00. Optimal cutpoints did not vary between regions.
      Youden's index for the combined algorithm varied between 0.78 and 1.00 by region.
      CONCLUSION: A brief version of the full CSI-D appears to share the favourable
      culture- and education-fair screening properties of the full assessment, despite
      considerable abbreviation. The feasibility and validity of the brief version
      still needs to be established in routine primary care.

PMID- 21845594
TI  - The prevalence and predictors of passive death wishes in Europe: a 2-year follow
      up of the Survey of Health, Ageing, and Retirement in Europe.
AB  - OBJECTIVES: This study evaluated regional variations (South, Centre, and North of
      Europe) in passive death wishes (wish to die) and predictors of passive death
      wishes, using a cross-national longitudinal design. METHODS: The Survey of
      Health, Ageing, and Retirement in Europe (SHARE) is a cross national European
      survey of individuals over the age of 50 and their spouse of any age. This study
      relied on wave 1 and 2 of SHARE. Passive death wishes were evaluated using an
      item from the Euro-D. A variety of clinical and sociodemographic variables were
      evaluated as potential predictors. RESULTS: The rate of passive death wishes was
      significantly lower in Northern Europe (4.6%) than in Southern (8.5%) and Central
      Europe (7.0%). Older adults, females, those reporting more depressive symptoms,
      more medical conditions, and lower levels of hope in wave 1 were more likely to
      report passive death wishes in wave 2, unrelated to geographic region. In
      contrast, passive death wishes reported in wave 1 were a stronger risk for
      passive death wishes in wave 2 for Northern Europeans than for Southern
      Europeans. CONCLUSIONS: Despite notable geographic differences in the prevalence
      rate of passive death wishes, most predictors evaluated in the present study
      function similarly across the three European regions.

PMID- 21845595
TI  - In-hospital death according to dementia diagnosis in acutely ill elderly
      patients: the REPOSI study.
AB  - OBJECTIVE: The aim of the study was to explore the association of dementia with
      in-hospital death in acutely ill medical patients. METHODS: Thirty-four internal
      medicine and 4 geriatric wards in Italy participated in the Registro Politerapie
      SIMI-REPOSI-study during 2008. One thousand three hundred and thirty two in
      patients aged 65 years or older were enrolled. Logistic regression models were
      used to evaluate the association of dementia with in-hospital death. Socio
      demographic characteristics, morbidity (single diseases and the Charlson Index),
      number of drugs, and adverse clinical events during hospitalization were
      considered as potential confounders. RESULTS: One hundred and seventeen
      participants were diagnosed as being affected by dementia. Patients with dementia
      were more likely to be women, older, to have cerebrovascular diseases, pneumonia,
      and a higher number of adverse clinical events during hospitalization. The
      percentage of patients affected by dementia who died during hospitalization was
      higher than that of patients without dementia (9.4 versus 4.9%). After
      multiadjustment, the diagnosis of dementia was associated with in-hospital death
      (OR = 2.1; 95% CI = 1.0-4.5). Having dementia and at least one adverse clinical
      event during hospitalization showed an additive effect on in-hospital mortality
      (OR = 20.7; 95% CI = 6.9-61.9). CONCLUSIONS: Acutely ill elderly patients
      affected by dementia are more likely to die shortly after hospital admission.
      Having dementia and adverse clinical events during hospital stay increases the
      risk of death.

PMID- 21845597
TI  - Depression in Alzheimer's disease: specificity of depressive symptoms using three
      different clinical criteria.
AB  - BACKGROUND: Previous studies report contradictory results on whether the symptoms
      of depression in Alzheimer's disease patients are the same as in cognitively
      normal persons. Thus, provisional criteria for depression in Alzheimer's disease
      (PDC-dAD) have been developed. AIM: To examine which symptoms in AD patients are
      significant in diagnosing depression according to PDC-dAD compared to those for
      the DSM-IV-TR and ICD-10 criteria. METHODS: We included 112 patients with
      Alzheimer's disease. They were interviewed by a psychiatrist who diagnosed
      depression according to PDC-dAD, DSM-IV-TR and ICD-10. Without knowledge of that
      diagnosis, trained nurses interviewed the caregivers of the patients using the
      Cornell scale for depression in dementia (CSDD). RESULTS: Mean age of the
      patients was 83.0 (s.d. 7.9), 77 (69.6%) were female. The proportion with
      depression according to each set of criteria was: PDC-dAD 53.5%, ICD-10, 47.3%
      and DSM-IV-TR, 34.8%. Sadness, loss of interest and agitation/retardation were
      the most prevalent symptoms in depressed subjects as evaluated by the
      psychiatrists. According to CSDD sadness, anxiety, suicidal thoughts, poor self
      esteem, multiple physical complaints and pessimism best distinguished the
      depressed patients from the non-depressed. In multiple logistic regression
      analyses poor self-esteem, delusion and multiple physical complaints best
      predicted depression using PDC-dAD criteria, whereas sadness, suicidal thoughts
      and poor self-esteem best predicted depression using ICD-10 and DSM-IV-TR.
      CONCLUSION: The most significant symptoms for a depressive disorder in AD are
      pretty much the same as for patients without dementia using the DSM-IV-TR and ICD
      10 criteria, whereas they differ using the PDC-dAD criteria.

PMID- 21845596
TI  - A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation
      trial following response to haloperidol treatment of psychosis and agitation in
      Alzheimer's disease.
AB  - OBJECTIVE: In patients with Alzheimer's disease (AD) with psychosis or agitation
      that respond to haloperidol treatment, to evaluate the risk of relapse following
      discontinuation. METHODS: In outpatients with AD with symptoms of psychosis or
      agitation, responders to 20 weeks of haloperidol (0.5-5 mg daily) were randomized
      to a 24-week, double-blind pilot trial of discontinuation on placebo versus
      continuation haloperidol. Phase A response criteria were minimum 50% reduction in
      three target symptoms, and improvement on the Clinical Global Impression-Change
      (CGI-C) score for psychosis/agitation. Phase B relapse criteria required 50%
      worsening in target symptoms and on the CGI-C. alpha = 0.1 was the significance
      criterion in this pilot study. RESULTS: Of 44 patients, 22 patients responded in
      Phase A. The sum score of target symptoms, and Brief Psychiatric Rating Scale
      (BPRS) psychosis and hostile suspiciousness factor scores, decreased in Phase A
      (p's < 0.001). Extrapyramidal signs increased in Phase A (p < 0.01). Of 22
      responders, 21 patients entered Phase B, and 20 had at least one follow-up visit.
      Four of 10 patients (40%) on continuation haloperidol relapsed compared to eight
      of 10 patients on placebo (80%, chi(2)  = 3.3, p = 0.07). In survival analyses,
      time to relapse was shorter on placebo than haloperidol (chi(2)  = 4.1, p =
      0.04). CONCLUSIONS: Haloperidol open treatment was efficacious, and relapse was
      greater on placebo than with haloperidol continuation. In patients with AD who
      have psychosis or agitation and respond to antipsychotic medication, the
      increased risk of relapse after discontinuation needs to be weighed against the
      side effects associated with continuing the medication.

PMID- 21845598
TI  - How do the PHQ-2, the PHQ-9 perform in aging services clients with cognitive
      impairment?
AB  - OBJECTIVE: To examine the performance of the Patient Health Questionnaire-2 (PHQ
      2) and the PHQ-9 in detecting current major depressive episode (MDE) in aging
      services care management clients who screen positive for cognitive impairment
      (CI). METHODS: Cross-sectional observational study of 236 care management clients
      ages >=60 years recruited from an Upstate NY aging services agency. The test
      characteristics of the PHQ-2 and PHQ-9 to screen for depression were calculated
      using the Structured Clinical Interview for DSM-IV (SCID) to identify MDE (gold
      standard). CI was identified with the Six-Item Screen (SIS). RESULTS:
      Participants had a mean age of 77 years, 68% female, 16% non-white, and 26% had
      less than a high school education. 16% of participants had CI identified by >=2
      errors on SIS. Of these, 41% had positive PHQ-2 (scores >=3), 43% had positive
      PHQ-9 (scores >=10), while 24% met criteria for MDE. In the sample with CI, the
      PHQ-2, using a cutoff of 3, had sensitivity = 0.78, specificity = 0.71, and
      receiver operating characteristic (ROC) area under the curve (AUC) = 0.81,
      compared with 0.79, 0.82, and 0.88, respectively, for those without CI. In the
      sample with CI, the PHQ-9, using a cutoff of 10, had sensitivity = 0.89,
      specificity = 0.71, and AUC = 0.85, compared with 0.85, 0.89, and 0.91,
      respectively, for those without CI. CONCLUSIONS: Cognitive status should be
      considered when using the PHQ as a depression screener due to poorer specificity
      in seniors with CI.

PMID- 21845599
TI  - Detecting cognitive impairment in individuals at risk for cardiovascular disease:
      the "Clock-in-the-Box" screening test.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance on the Clock
      in-the-Box (CIB), a screening measure for cognitive function, relative to
      neuropsychological testing in an older population with cardiovascular risk.
      METHODS: A prospective cohort of older patients (>50 years) with cardiovascular
      risk was recruited to perform the CIB and complete a brief neuropsychological
      battery consisting of Trailmaking tests, the Hopkins Verbal Learning Test (HVLT),
      and fluency tasks. Performance on the CIB was scored according to standard
      criteria (range 0-8, 0-worst). The performance on the total CIB, working memory
      subscale (CIB-WM), and planning/organization (COB-PO) was compared to
      neuropsychological measures. RESULTS: The cohort (n = 127) was older (age 67 +/-
      7 years) and diverse with 33% female (n = 42) and 42% non-white race (n = 53).
      Cardiac risk factors were prevalent: hypertension (83%), hyperlipidemia (74%),
      overweight (84%), diabetes (48%), prior cardiac disease (39%), and smoking (11%).
      The CIB (mean 6.5 +/- 1.3) took 84 +/- 21 s on average to complete and had good
      inter-rater reliability (kappa = 0.809, p < 0.01). The CIB-WM subscale was
      significantly correlated with performance on Trailmaking B and HVLT learning,
      recall, and recognition. The CIB-PO subscale was significantly associated with
      semantic and phonemic fluency, Trailmaking B, and HVLT learning and recall. In
      regression modeling, CIB-WM significantly predicted performance on HVLT learning,
      recall, and retention. CIB-PO subscale predicted performance on Trailmaking B,
      HVLT learning, and HVLT recall. CONCLUSIONS: The CIB is a brief cognitive
      screening instrument with good reliability and predictive validity in a CV risk
      population. The CIB-WM and CIB-PO subscales could provide utility for clinicians.

PMID- 21845600
TI  - Test Your Memory test: diagnostic utility in a memory clinic population.
AB  - BACKGROUND: Test Your Memory (TYM) test is a recently described cognitive test
      instrument designed to be self-administered under medical supervision. The
      pragmatic role of such self-administered tests in cognitive clinics has not
      previously been examined. We investigated the diagnostic utility of the TYM as an
      independent test to differentiate patients with and without dementia at initial
      clinical diagnostic interview in dedicated memory clinics. METHODS: TYM was
      administered to consecutive new patient referrals to two memory clinics
      independent of other tests [Mini-Mental State Examination (MMSE) and the
      Addenbrooke's Cognitive Examination-Revised] which were used to establish
      diagnoses according to standard diagnostic criteria (DSM-IV), and results were
      compared. RESULTS: In a cohort of 224 patients, 35% fulfilling clinical
      diagnostic criteria for dementia, TYM proved easy to use and acceptable to
      patients. Downward adjustment of the TYM test cutoff to <=30/50, compared to
      <=42/50 used in the index study, proved necessary to maximise test accuracy and
      specificity. Using this revised cutoff, TYM showed comparable diagnostic utility
      (sensitivity 0.73, specificity 0.88, positive predictive value 0.77, negative
      predictive value 0.86 and area under receiver operating characteristic curve
      0.89) to the MMSE and the Addenbrooke's Cognitive Examination-Revised for the
      differentiation of cases of dementia from non-dementia. CONCLUSIONS: TYM is a
      useful screening test in the cognitive function clinic setting, with patients who
      fall below the designated cutoff requiring further investigation to ascertain a
      cause for their cognitive impairment. Self-administered tests such as TYM may be
      of particular value in situations where clinician time is limited.

PMID- 21845601
TI  - The effect of age on prevalence, type and diagnosis of personality disorder in
      psychiatric inpatients.
AB  - OBJECTIVE: To examine age-related differences in personality disorder (PD)
      comorbidity and in their diagnosis in psychiatric inpatients. METHODS: Two
      hundred thirty-one consenting adults consecutively admitted to inpatient
      psychiatry units and aged between the age of 18 and 100 were assessed using the
      Structured Clinical Interview for DSM IV Axis I and II (SCID-I and -II), after
      excluding cognitively impaired, non-English speaking, short stay and respite
      patients. Hospital files were audited for clinical diagnoses, in particular for
      recorded PDs. Rates of PD prevalence and clinician diagnosis were compared for
      young (n = 76), middle-age (n = 57) and older (n = 98) patients. RESULTS:
      Significant personality comorbidity was evident at all ages, but rates were
      lowest in the older group. PD was present in 73.7% of young, 71.9% of middle-age
      and 58.8% of older patients. Complex PD was more common in young patients. Only
      19.8% of PDs were noted by their clinicians to have PD. CONCLUSION: Comorbid PD
      is common in psychiatric inpatient groups regardless of age but seldom diagnosed
      clinically.

PMID- 21845602
TI  - Reliability of the Rowland Universal Dementia Assessment Scale (RUDAS) via video
      conferencing.

PMID- 21845603
TI  - Biocatalytic pre-treatment processes of cotton: industrial application of
      academic research.

PMID- 21845730
TI  - Is the adhesive material secreted by sea urchin tube feet species-specific?
AB  - Sea urchin adoral tube feet are highly specialized organs that have evolved to
      provide efficient attachment to the substratum. They consist of a disk and a stem
      that together form a functional unit. Tube foot disk tenacity (adhesive force per
      unit area) and stem mechanical properties (e.g., stiffness) vary between species
      but are apparently not correlated with sea urchin taxa or habitats. Moreover,
      ultrastructural studies of sea urchin disk epidermis pointed out differences in
      the internal organization of the adhesive secretory granules among species. This
      prompted us to look for interspecific variability in the composition of echinoid
      adhesive secretions, which could explain the observed variability in adhesive
      granule ultrastructure and disk tenacity. Antisera raised against the footprint
      material of Sphaerechinus granularis (S. granularis) were first used to locate
      the origin of adhesive footprint constituents in tube feet by taking advantage of
      the polyclonal character of the generated antibodies. Immunohistochemical assays
      showed that the antibodies specifically labeled the adhesive secretory cells of
      the disk epidermis in the tube feet of S. granularis. The antibodies were then
      used on tube foot histological sections from seven other sea urchin species to
      shed some light on the variability of their adhesive substances by looking for
      antibody cross-reactivity. Surprisingly, no labeling was observed in any of the
      species tested. These results indicate that unlike the adhesive secretions of
      asteroids, those of echinoids do not share common epitopes on their constituents
      and thus would be "species-specific." In sea urchins, variations in the
      composition of adhesive secretions could therefore explain interspecific
      differences in disk tenacity and in adhesive granule ultrastructure.

PMID- 21845732
TI  - Cranial muscles of the anurans Leiopelma hochstetteri and Ascaphus truei and the
      homologies of the mandibular adductors in Lissamphibia and other gnathostomes.
AB  - The frogs Ascaphus truei and Leiopelma hochstetteri are members of the most basal
      lineages of extant anurans. Their cranial muscles have not been previously
      described in full and are investigated here by dissection. Comparison of these
      taxa is used to review a controversy regarding the homologies of the jaw adductor
      muscles in Lissamphibia, to place these homologies in a wider gnathostome
      context, and to define features that may be useful for cladistic analysis of
      Anura. A new muscle is defined in Ascaphus and is designated m. levator anguli
      oris. The differences noted between Ascaphus and Leiopelma are in the penetration
      of the jaw adductor muscles by the mandibular nerve (V3). In the traditional view
      of this anatomy, the paths of the trigeminal nerve branches define homologous
      muscles. This scheme results in major differences among frogs, salamanders, and
      caecilians. The alternative view is that the topology of origins, insertions, and
      fiber directions are defining features, and the nerves penetrate the muscle mass
      in a variable way. The results given here support the latter view. A new model is
      proposed for Lissamphibia, whereby the adductor posterior (levator articularis)
      is a separate entity, and the rest of the adductor mass is configured around it
      as a folded sheet. This hypothesis is examined in other gnathostomes, including
      coelacanth and lungfish, and a possible sequence for the evolution of the jaw
      muscles is demonstrated. In this system, the main jaw adductor in teleost fish is
      not considered homologous with that of tetrapods. This hypothesis is consistent
      with available data on the domain of expression of the homeobox gene engrailed 2,
      which has previously not been considered indicative of homology. Terminology is
      discussed, and "adductor mandibulae" is preferred to "levator mandibulae" to
      align with usage in other gnathostomes.

PMID- 21845731
TI  - Uterine and chorioallantoic angiogenesis and changes in the uterine epithelium
      during gestation in the viviparous lizard, niveoscincus conventryi (Squamata:
      Scincidae).
AB  - We used immunofluorescent confocal microscopy and scanning electron microscopy to
      quantify uterine vascularity and to describe uterine surface morphology during
      gestation in pregnant females of the lecithotrophic lizard Niveoscincus
      coventryi. As uterine angiogenesis and epithelial cell morphology are thought to
      be under progesterone control, we studied the effect of a progesterone receptor
      antagonist (mifepristone) on uterine and chorioallantoic microvasculature and
      features of the uterine epithelial surfaces. Although intussuceptive angiogenesis
      was observed in both, uterine and chorioallantoic, vascular beds during
      gestation, the only significant increases were in the diameters of the uterine
      vessels. An ellipsoid vessel-dense area grows in the mesometrial hemisphere of
      the developing conceptus, which parallels the expansion of the allantois to form
      the chorioallantoic placenta. Uterine surface topography changed during
      gestation. In particular, uterine blood vessels bulge over the luminal surface to
      form marked ridges on the uterine embryonic hemisphere, especially during the
      last stage of pregnancy, and ciliated cells are maintained in the embryonic and
      abembryonic hemispheres but disappear in both the mesometrial and antimesometrial
      poles. This distinct regionalization of uterine ridges and ciliated cells in the
      uterine surface and in the shape of the epithelial component of the chorion might
      be related to the function of both chorioallantoic and yolk sac placentae during
      gestation. There was no significant difference between females treated with or
      without mifepristone, which may be related to the partial function of
      mifepristone as a progestin antagonist and/or with the function and time of
      action of progesterone in the uterus during gestation in N. coventryi.
      Differences in the pattern of angiogenesis and uterine surface morphology during
      gestation among squamates may be related to the functional diversity of the
      uterine component of the different placentae and probably reflect its diverse
      evolutionary history.

PMID- 21845733
TI  - Mechanisms of cell death of thymocytes induced by polyunsaturated,
      monounsaturated and trans-fatty acids.
AB  - Polyunsaturated fatty acids (PUFAs) are rapidly cytotoxic to isolated murine
      thymocytes, and the degree of cell death has been correlated with changes in
      membrane fluidity, elevation of intracellular calcium concentration and
      generation of reactive oxygen species. We have compared the degree of cell death
      and increase in membrane fluidity of C-20 and C-22 omega-3 and 6 PUFAs to those
      induced by monounsaturated and trans-fatty acids, and find that concentrations
      which induce comparable increases in membrane fluidity do not cause comparable
      cell death. The C-18 omega-6 causes a decrease in membrane fluidity, yet is the
      most potent in causing cell death. Omega-6 PUFAs are more cytotoxic than omega-3
      PUFAs, while monounsaturated and trans-fats show little cytotoxicity and only at
      much higher concentrations. Cell death is preceded by reductions of both plasma
      and mitochondrial membrane potential, and occurs via apoptosis. These results
      indicate that cell death is due to mechanisms other than changes in membrane
      fluidity.

PMID- 21845734
TI  - USP7 regulates the stability and function of HLTF through deubiquitination.
AB  - Human helicase-like transcription factor (HLTF) is a functional homologue of
      yeast Rad5 that regulates error-free replication through DNA lesions. HLTF
      promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear
      antigen (PCNA) that is required for maintaining genomic stability. Here, we
      identified the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a
      novel regulator of HLTF stability. We found that USP7 interacted with and
      stabilized HLTF after genotoxic stress. Furthermore, USP7 mediated
      deubiquitination significantly prolonged the half-life of HLTF, which in turn
      increased PCNA polyubiquitination. More intriguingly, silencing of USP7 rendered
      A549 cells highly sensitive to DNA damage and over-expression of HLTF attenuated
      this sensitivity. Thus, our results delineate a previously unknown USP7-HLTF-PCNA
      molecular network controlling DNA damage response.

PMID- 21845735
TI  - Human immunodeficiency virus type 1 Nef in human monocyte-like cell line THP-1
      expands treg cells via toll-like receptor 2.
AB  - CD4(+) CD25(+) regulatory T cells (Tregs) represent a unique T-cell lineage that
      is endowed with the ability to actively suppress immune responses in order to
      inhibit pathogenic damage resulting from over activation of the immune system. In
      human immunodeficiency virus-1 (HIV-1) infection, suppression of the immune
      response by Tregs appears to play an opposing role that promotes chronic viral
      infection. Treg expansion is known as a marker of the severity of HIV infection
      and as a potential prognostic marker of disease progression. HIV-1 Nef is one of
      the earliest expressed viral regulatory genes whose expression may play an
      important role in regulating Treg cells. We established a THP-1 cell line stably
      expressing HIV-1 Nef and showed that Nef protein was a potent factor for
      increasing Treg numbers in vitro. We further found that TLR2 plays a critical
      role in the increase in Treg cells induced by Nef using TLR2-specific siRNA. Our
      results suggest new strategies for therapeutic and preventive interventions of
      HIV infection.

PMID- 21845736
TI  - Deciphering the regulatory codes in bacterial genomes.
AB  - Interactions between cis-regulatory elements and trans-acting factors are
      fundamental for cellular functions such as transcription. With the revolution in
      microarrays and sequencing technologies, genome-wide binding locations of trans
      acting factors are being determined in large numbers. The richness of the genome
      scale information has revealed that the nature of the bacterial transcriptome and
      regulome are considerably more complex than previously expected. In addition, the
      emerging view of the bacterial transcriptome is revising the concept of the
      operon organization of the genome. This review describes current advances in the
      genome-scale analysis of the interaction between cis-regulatory elements and
      trans-acting factors in microorganisms.

PMID- 21845737
TI  - Characterization of skin abnormalities in a mouse model of osteogenesis
      imperfecta using high resolution magnetic resonance imaging and Fourier transform
      infrared imaging spectroscopy.
AB  - Evaluation of the skin phenotype in osteogenesis imperfecta (OI) typically
      involves biochemical measurements, such as histologic or biochemical assessment
      of the collagen produced from biopsy-derived dermal fibroblasts. As an
      alternative, the current study utilized non-invasive magnetic resonance imaging
      (MRI) microscopy and optical spectroscopy to define biophysical characteristics
      of skin in an animal model of OI. MRI of skin harvested from control, homozygous
      oim/oim and heterozygous oim/+ mice demonstrated several differences in anatomic
      and biophysical properties. Fourier transform infrared imaging spectroscopy (FT
      IRIS) was used to interpret observed MRI signal characteristics in terms of
      chemical composition. Differences between wild-type and OI mouse skin included
      the appearance of a collagen-depleted lower dermal layer containing prominent
      hair follicles in the oim/oim mice, accounting for 55% of skin thickness in
      these. The MRI magnetization transfer rate was lower by 50% in this layer as
      compared to the upper dermis, consistent with lower collagen content. The MRI
      transverse relaxation time, T2, was greater by 30% in the dermis of the oim/oim
      mice compared to controls, consistent with a more highly hydrated collagen
      network. Similarly, an FT-IRIS-defined measure of collagen integrity was 30%
      lower in the oim/oim mice. We conclude that characterization of phenotypic
      differences between the skin of OI and wild-type mice by MRI and FT-IRIS is
      feasible, and that these techniques provide powerful complementary approaches for
      the analysis of the skin phenotype in animal models of disease.

PMID- 21845739
TI  - A simple and low-cost device for generating hyperpolarized contrast agents using
      parahydrogen.
AB  - A detailed description of the construction and use of a device for
      hyperpolarization of select contrast agents is presented. The device is based on
      molecular incorporation of the spin-order inherent to parahydrogen, followed by
      order transfer to a metastable heteronuclear alignment. Design considerations and
      experimental results relating to catalyst/solvent choice and handling, solvent
      heating, efficient gas entrainment and spin-order transfer are described. The
      resulting degree of hyperpolarization is shown to be substantial, ranging from a
      few to over 50%, depending on the choice of target molecule. Finally, the use of
      the hyperpolarized agent is demonstrated in a series of in vivo images.

PMID- 21845738
TI  - T2 measurement of J-coupled metabolites in the human brain at 3T.
AB  - Proton T(2) relaxation times of metabolites in the human brain were measured
      using point resolved spectroscopy at 3T in vivo. Four echo times (54, 112, 246
      and 374 ms) were selected from numerical and phantom analyses for effective
      detection of the glutamate multiplet at ~ 2.35 ppm. In vivo data were obtained
      from medial and left occipital cortices of five healthy volunteers. The cortices
      contained predominantly gray and white matter, respectively. Spectra were
      analyzed with LCModel software using volume-localized calculated spectra of brain
      metabolites. The estimate of the signal strength vs. TE was fitted to a
      monoexponential function for estimation of apparent T(2) (T(2)(?)). T(2)(?) was
      estimated to be similar between the brain regions for creatine, choline,
      glutamate and myo-inositol, but significantly different for N-acetylaspartate
      singlet and multiplet. T(2)(?)s of glutamate and myo-inositol were measured as
      181 +/- 16 and 197 +/- 14 ms (mean +/- SD, N = 5) for medial occipital cortices,
      and 180 +/- 12 and 196 +/- 17 ms for left occipital cortices, respectively.

PMID- 21845740
TI  - Three-dimensional transperineal ultrasound findings associated with anal
      incontinence after intrapartum sphincter tears in primiparous women.
AB  - OBJECTIVE: Three-dimensional transperineal sonography (3D-TPS) performed in women
      following third- or fourth-degree intrapartum tears repaired with the overlapping
      technique demonstrates characteristic signs. The aim of this study was to
      investigate the correlation of these signs with clinical complaints of
      incontinence. METHODS: This was a prospective observational study. Sixty
      primiparous women underwent 3D-TPS 3-42 (mean, 10.6) months after surgical repair
      of third- or fourth-degree postpartum sphincter tears with the overlapping
      technique and were evaluated for clinical degree of incontinence using the St
      Mark's Incontinence Score (SMIS) questionnaire. The following signs were assessed
      on 3D-TPS: interruption of the internal anal sphincter or external anal
      sphincter, 'half moon' sign, changes in the mucosal folds and thickening of the
      external anal sphincter in the area of sphincter repair. As a comparison group,
      27 primiparous women after normal vaginal delivery, without clinically recognized
      anal sphincter tears, were evaluated similarly, 3-37 (mean, 9.9) months
      postpartum. RESULTS: Abnormal sonographic signs were apparent in 35 (58.3%) of 60
      women in the study group, and 39 (65%) of 60 had some clinical complaints of
      incontinence 3-42 months after delivery, most of a mild degree. Higher SMIS
      results were found in women of the study group than in those of the comparison
      group (mean (SD) 2.80 (0.481) vs. 1.15 (0.365); P = 0.018). The rates of
      incontinence were similar between the women in the study group with normal
      ultrasound findings and the women in the comparison group (9/25 vs. 10/27;
      relative risk (RR) = 0.97, 95% CI, 0.47-1.97). CONCLUSIONS: Sonographic signs of
      anal sphincter tear and repair had disappeared at follow-up examination in almost
      half of the patients, and therefore this examination should be deferred from the
      early postpartum period. A substantial proportion of women report some complaint
      of incontinence after sphincter repair, most of a slight degree. Such complaints
      are associated with abnormal 3D-TPS findings at follow up, while in women with a
      normal 3D-TPS scan the rate of incontinence complaints is similar to that in
      women after normal delivery.

PMID- 21845741
TI  - Value of three-dimensional power Doppler to predict clinical and histological
      response to neoadjuvant chemotherapy in locally advanced cervical carcinoma.
AB  - OBJECTIVE: Platinum-based neoadjuvant chemotherapy followed by radical
      hysterectomy is an alternative therapeutic strategy for locally advanced cervical
      carcinoma but variables used to predict chemotherapy response are not well
      defined. We investigated the potential of three-dimensional (3D) power Doppler in
      predicting response to neoadjuvant chemotherapy. METHODS: We enrolled 61 eligible
      patients with locally advanced cervical carcinoma who underwent neoadjuvant
      chemotherapy followed by surgery or radiation. Before the initial chemotherapy,
      we measured 3D power Doppler vascular indices, including vascularization index
      (VI), flow index (FI) and vascularization flow index (VFI), of the whole cervical
      carcinoma. We also measured two-dimensional (2D) hemodynamic parameters, such as
      resistance index and pulsatility index, at three random spots inside the tumor.
      The associations of all parameters with clinical and histological responses to
      chemotherapy were evaluated through univariable and multiple logistic regression
      analysis. RESULTS: The clinical and histological response rates to chemotherapy
      were 70.5% and 70.7%, respectively. Univariable logistic regression analysis
      showed that VI, FI and VFI were significantly higher in clinical responders than
      in non-responders (P < 0.05), and that FI was significantly higher in
      histological responders (P = 0.012). Multiple logistic regression analysis showed
      that FI was the only significant factor associated with both clinical and
      histological responses. The best FI cut-off values were 35.3 and 37.3 for
      clinical response and histological response, respectively (with sensitivity 86.0%
      and 73.2%, and specificity 72.2% and 64.7%). Interestingly, none of the 2D
      hemodynamic parameters was significantly correlated with either response.
      CONCLUSION: FI is a potential marker for predicting both clinical and
      histological responses to chemotherapy in patients with locally advanced cervical
      carcinoma.

PMID- 21845742
TI  - First-trimester detection of structural abnormalities and the role of aneuploidy
      markers.
AB  - OBJECTIVES: To determine the sensitivity of first-trimester ultrasound for
      diagnosing different structural anomalies in chromosomally normal pregnancies,
      and to establish the role of aneuploidy markers in the detection of
      abnormalities. METHODS: This was a retrospective study of chromosomally normal
      singleton pregnancies with an 11-14-week scan performed in our center during 2002
      2009. The ultrasound examination included an early fetal anatomy survey and
      assessment of nuchal translucency, ductus venosus blood flow and nasal bone.
      RESULTS: Among 13 723 scanned first-trimester pregnancies with no genetic
      anomalies and complete follow-up, 439 fetuses (3.2%) were found to present with
      structural anomalies (194 with major anomalies and 245 with only minor
      anomalies). Forty-nine per cent of major structural anomalies were detected
      during the first-trimester scan, the highest rates corresponding to acrania
      (17/17), holoprosencephaly (three of three), hypoplastic left heart syndrome
      (10/10), omphalocele (six of six), megacystis (seven of eight) and hydrops (eight
      of nine). Higher than expected detection rates were obtained for skeletal (69%)
      and cardiac (57%) defects, coincidentally showing the highest presence of an
      increased nuchal translucency or abnormal ductus venosus blood flow (38% and 52%,
      respectively). The finding of an absent nasal bone did not appear to be
      associated with structural defects. CONCLUSION: About half of major structural
      abnormalities can be diagnosed in the first trimester. Increased nuchal
      translucency or abnormal ductus venosus blood flow appear to be associated with
      cardiac and skeletal defects and may facilitate early detection.

PMID- 21845743
TI  - Cervical length at 30-32 weeks and the risk of Cesarean delivery in twin
      pregnancies.
AB  - OBJECTIVES: To estimate the association between the cervical length (CL)
      measurement at 30-32 weeks and the mode of delivery in twin pregnancies. METHODS:
      This was a retrospective study of a cohort, from 2005-2010, of 265 twin
      pregnancies with a CL measurement at 30-32 weeks. We compared the CL measurement
      at 30-32 weeks based on mode of delivery. We then analyzed our data across four
      subgroups, based on the CL measurement quartiles at 30-32 weeks. We performed
      this analysis in all patients, and also performed a planned subgroup analysis of
      130 patients who attempted a vaginal delivery. RESULTS: In all patients,
      including those who attempted a vaginal delivery, the mean CL at 30-32 weeks was
      significantly shorter in women who delivered vaginally compared with women who
      had a Cesarean section. The likelihood of Cesarean delivery increased
      significantly with increasing CL measurement across the groups defined by
      measurement quartiles. On adjusted analysis controlling for maternal age, race,
      in-vitro fertilization, chorionicity, induction of labor and prior vaginal
      delivery, the CL measurement at 30-32 weeks was independently associated with
      mode of delivery. CONCLUSIONS: In twin pregnancies, the CL at 30-32 weeks is
      significantly associated with the likelihood of Cesarean delivery. A longer CL
      may represent underdevelopment of the uterus, leading to a higher risk of
      Cesarean delivery in labor at term.

PMID- 21845744
TI  - Ultrasonographic appearance of metastatic non-gynecological pelvic tumors.
AB  - OBJECTIVE: To describe the ultrasound (sonomorphologic and vascular)
      characteristics of metastatic non-gynecological pelvic tumors, and to identify
      ultrasound characteristics typical of the most common non-gynecological pelvic
      tumors. METHODS: In 92 patients with a pelvic mass who had undergone ultrasound
      examination with subsequent surgery or tru-cut biopsy revealing a metastatic non
      gynecological tumor origin, we analyzed retrospectively the sonomorphologic and
      vascular parameters. All parameters were evaluated for the whole group of non
      gynecological tumors as well as separately for each specific tumor type. The
      findings were compared with those from 100 women with epithelial ovarian cancer.
      RESULTS: We found that CA 125, size of tumor, echogenicity, homogeneity of solid
      portion, mobility, and presence of ovarian crescent sign, parenchymal metastases
      and suspicious necrosis were individual statistically significant discriminators
      (P < 0.01) between the metastatic non-gynecological tumor group and the
      epithelial ovarian cancer group. CONCLUSIONS: Metastatic non-gynecological tumors
      in the pelvis have a significantly different sonomorphologic pattern compared
      with primary epithelial ovarian cancer. This pattern is dependent on the primary
      origin of the tumor. Doppler parameters, however, cannot differentiate between
      primary ovarian cancer and metastatic non-gynecological tumors.

PMID- 21845745
TI  - [Current situation and future development in modernization of TCM].

PMID- 21845746
TI  - [Marrow mesenchymal stem cell transplantation with sodium alginate gel for repair
      of spinal cord injury in mice].
AB  - OBJECTIVE: To investigate the effects of sodium alginate gels on marrow
      mesenchymal stem cell transplantation for repair of spinal cord injury (SCI) in
      mice. METHODS: In the present study, effects of different sterilization methods
      and concentrations of sodium alginate gels were examined. Marrow mesenchymal stem
      cells (mMSCs) were isolated from mice and cultured. Cells were cultured with
      sodium alginate gels and MTT assay was applied to determine the cell viability.
      Mice spinal cord injury was induced by spinal cord transection. mMSCs were
      transplanted into the cavity of injured spinal cord with sodium alginate gels.
      The effects of sodium alginate gel were assessed by BMS scales and
      immunofluorescence staining for NF-200. RESULTS: Compared with liquid form, solid
      form sodium alginate gel prepared with high pressure vapor sterilization had a
      better effect on cell viability. SCI mice treated with 10 % sodium alginate gel
      and mMSCs achieved higher score in BMS scale as well as higher expression of NF
      200 compared with the untreated SCI group. CONCLUSION: Sodium alginate gel
      prepared with solid form sterilization induces mMSCs proliferation and thus can
      be used as the carrier of stem cell in treatment of SCI.

PMID- 21845747
TI  - [Effect of purple sweet potato on lipid metabolism and oxidative stress in
      hyperlipidemic rats].
AB  - OBJECTIVE: To investigate the effect of purple sweet potato on lipid metabolism
      and oxidative stress in hyperlipidemic rats. METHODS: Forty male SD rats were
      randomly divided into 4 groups: normal control group, high-fat control group,
      high purple sweet potato groups, low purple sweet potato group. The rats were fed
      with different diets for 6w respectively. RESULTS: Serum TC, TG levels were
      significantly lower in high dosage group than in high-fat control group; while
      only serum TG was significantly lower in low dosage group than in high-fat
      control group, these changes started at the third week and lasted to the end of
      experiment. Serum LDL-C and AI levels were significantly lower in high and low
      dosage group than in high-fat control group, whereas, serum HDL-C was
      significantly higher than that in high-fat control group at w3 and lasted to the
      end of experiment. Serum SOD was significantly higher in high and low dosage
      group than in high-fat control group, whereas, serum MDA was significantly lower
      than that in high-fat control group at w6. CONCLUSION: Purple sweet potato can
      decrease serum lipids and reduce hepatic oxidative stress in hyperlipidemic rats.

PMID- 21845748
TI  - [Anti-tumor activity of components isolated from purple sweet potato
      polysaccharides].
AB  - OBJECTIVE: To isolate and purify components from polysaccharides of purple sweet
      potato (PPSP) and to test their anti-tumor activity. METHODS: DEAE-Cellulose and
      CM-Cellulose exchange chromatography were applied to separate components of PPSP.
      The anti-tumor activities of each component were measured by MTT assay on Hela
      and HepG(2) cells and their monosaccharide composition were analyzed by TLC
      chromatography, followed by infrared spectroscopy studies. RESULTS: Through weak
      anion exchange chromatography and gradient elution by sodium chloride solution,
      four components were separated and named as PPSP, PPSPII, PPSPIII and PPSPIV,
      respectively. MTT tests showed that PPSP II and PPSPIII inhibited Hela and HepG2
      tumor cells in a certain extent. The structural analysis revealed that PPSPI was
      mainly composed of glucose and galactose, PPSP II was composed of glucose and had
      a typical absorption peak of beta-D-glucose chitosan pyranose, PPSP III was a
      glycoprotein showing a protein absorption peak. CONCLUSION: Four components were
      separated from PPSP successfully, among which PPSP II and PPSP III shows anti
      tumor activities on Hela and HepG(2) cells in vitro.

PMID- 21845749
TI  - [Effect of purple sweet potato flavonoids on metabolism of glucose and lipids in
      diabetic rats].
AB  - OBJECTIVE: To investigate the effects of purple sweet potato flavonoids (PSPF) on
      blood glucose and lipids levels in diabetic rats. METHODS: Diabetes was induced
      by intraperitoneal injection of streptozotocin (STZ, 65 mg.kg(-1)) in rats. The
      changes of fasting blood glucose and lipids levels in serum and body weight, food
      and fluid intake of diabetic rats treated with PSPF were examined. RESULTS:
      Diabetic symptoms were ameliorated after rats were fed with PSPF. The fasting
      blood glucose (FBG), GSP, TC, TG, LDL-C were decreased and serum HDL-C levels
      were increased (P<0.01) in high, medium dose PSPF groups; while FBG, serum GSP,
      TG, LDL-C were also improved in low dose group (P<0.05 or P<0.01). CONCLUSION:
      Purple sweet potato flavonoids can decrease the blood glucose and lipids levels
      in diabetic rats.

PMID- 21845750
TI  - [Components of myrsinane-type diterpenes from Euphorbia prolifera].
AB  - OBJECTIVE: To extract and isolate the component from myrsinane-type diterpenes of
      Euphorbia prolifera. METHODS: Petroleum extraction and chromatography on the
      silica gel were used to extract and isolate the diterpenes of Euphorbia
      prolifera. RESULTS: Eight components of myrsinol diterpenes were isolated,
      namely: Proliferin A(1), Proliferin B (2), Proliferin C(3), Proliferin D(4),
      Euphorprolitherin B(5), Euphorprolitherin D(6), SPr5(7) and 14-desoxo-3-O
      prorionyl-5, 15-di-O-acetyl-7-O-nicotinoyl-myrsinol-14beta-acetate(8). Their
      structures were identified with mass-spectroscopic methods and NMR techniques.
      The cytotoxicity of compounds 1, 2, and 4 against cancer cells was evaluated,
      with compound 1 being active against A2780 cancer cells (IC(50) 7.7 MUmol/L).
      CONCLUSION: Myrsinane-type diterpene Proliferin A from Euphorbia prolifera shows
      cytotoxic effect against human ovarian cancer cell line A2780.

PMID- 21845751
TI  - [Comparison of behavioral effects of psychoactive drugs between two strains of
      mice].
AB  - OBJECTIVE: To compare the behavioral effects of psychoactive drugs between two
      strains of mice. METHODS: The Kunming (KM) and ICR mice were injected
      intraperitoneally with caffeine (3, 10, 30, 100 mg/kg), ephedrine (3, 10, 30, 100
      mg/kg), diazepam (1, 3,1 0 mg/kg) and chloral hydrate (10, 30, 100 mg/kg),
      respectively. Ten min after injection, the locomotor activity in the open field
      was recorded for 2 h. The total distance, the distance ratio to total distance
      and the time in central region were analyzed for each drugs. Thirty min after
      injection, the latent time in the passive avoidance test was measured in a
      shuttle box. RESULTS: Caffeine and diazepam prolonged the latent time, and
      ephedrine and chloral hydrate decreased the latent time, but there were no
      differences between the two strains. The two strains of mice exhibited
      significant differences in the total distance after injection of ephedrine 10
      mg/kg, diazepam 3 mg/kg and chloral hydrate 100 mg/kg. Compared to KM mice, ICR
      mice exhibited an increase in the distance ratio and the time in central region
      after injection of ephedrine 10-100 mg/kg, but a decrease after diazepam 3-10
      mg/kg. CONCLUSION: KM and ICR mice show no differences in latent time, but
      significant differences in the total distance, the distance ratio and the time in
      central region in the locomotor activity. Therefore, selection of mouse strains
      is important in the study of psychoactive drugs.

PMID- 21845752
TI  - [Protective effect of Jiangbaiweiyan tablet on ethanol-induced gastric mucosa
      injury in rats].
AB  - OBJECTIVE: To investigate the effect of Jiangbaiweiyan tablet, a Chinese medicine
      compound composed of Alpinta Officinarum, Cyperus Rotundus, Bulbus Lilii and
      Rlindera Strychnifolia, on ethanol-induced gastric mucosa injury in rats.
      METHODS: Acute gastric ulcer was induced in rats with absolute ethyl alcohol. The
      ulcer index was used to evaluate the extent of the gastric mucosa injury.
      RESULTS: The ulcer indexes of the model group, the mid-dose (1.08 g x kg(-1) x d
      (-1)1) and high-dose (2.16 g x kg(-1) x d-(-1)) of Jiangbaiweiyan tablet groups
      were 141.58+/-47.43, 24.83+/-23.04 and 2.12+/-2.58, respectively (P<0.01).
      CONCLUSION: Jiangbaiweiyan tablet has protective effects on ethanol-induced
      gastric mucosa injury in rats, which may be related to anti-oxidation and
      enhancing tissue regeneration capacity.

PMID- 21845753
TI  - [Study on determination and pharmacokinetics of metabolites from Folium Mori
      extract in rats].
AB  - OBJECTIVE: To establish a RP-HPLC method for simultaneous determination of total
      quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of
      Folium Mori extract (FME). METHODS: After a single dose of FME (110 mg/kg) was
      taken, rat plasma samples were collected. The samples were hydrolyzed with
      hydrochloric acid (c=3.0 mol/L), the mixed solution was extracted with ether
      acetone mixture. The total quercetin, kaempferol and isorhamnetin in plasma
      samples were determined by HPLC, pharmacokinetic parameters were calculated by
      DAS 3.0 software. RESULTS: The method was linear over the concentration ranges of
      0.0545-8.70, 0.0954-14.7 and 0.0545-8.55 MUg/ml for quercetin, kaempferol and
      isorhamnetin, respectively (r=0.9979, 0.9993, 0.9981). The absolute recoveries
      were 85.3%-86.1%, 79.4%-86.7% and 62.8%-89.7%, respectively and the assay
      recoveries were all from 94.7% to 107%. The relative standard deviation (RSD) of
      intra-and inter-day were less than 9.5% and 9.8%, respectively. The main
      pharmacokinetic parameters were as follows: T(1/2z) was 92.7, 67.9 and 54.2 h;
      Tmax was 0.400, 0.400 and 3.87 h; AUC(0-infinity) was 68.0, 67.5 and 32.8 mg/h/L;
      MRT(0-infinity) was 128, 85.2 and 72.0 h for quercetin, kaempferol and
      isorhamnetin, respectively. CONCLUSION: The method established in this study is
      accurate, reliable and reproducible, and can be applied for determination of
      total quercetin, kaempferol and isorhamnetin in rat plasma after oral
      administration of FME; the pharmacokinetic studies showed that the distribution
      of drugs is rapid and elimination is very slow.

PMID- 21845754
TI  - [Inhibitive effect of C-21 steroidal glycosides of Cynanchum auriculatum on rat
      glioma cells in vitro].
AB  - OBJECTIVE: To evaluate the inhibitive effect of C-21 steroidal glycosides from
      the root of Cynanchum auriculatum (CGB) on rat glioma C6 cells. METHODS: C6 cells
      were treated with CGB for 24, 48,72 h at concentration of 30, 60, 120 mg/L,
      respectively. MTT assay was used for evaluating cell viability; fluorescence
      activated cell sorting analysis after Annexin V/propidium iodide staining or
      single propidium iodide staining was used to test cell apoptosis and cell cycle.
      RESULTS: CGB at 30, 60, 120 mg/L concentration-dependently decreased C6 cell
      viability (P<0.001). CGB at 60 and 120 mg/L induced C6 cell apoptosis and cell
      cycle arrest. The fraction of G0/G1 cells was increased (P<0.05) and that of S
      phase cells was decreased (P<0.01). CONCLUSION: CGB can inhibit the growth of rat
      glioma C6 cells, and induce apoptosis and G0/G1 cell cycle arrest.

PMID- 21845755
TI  - [Comparison on antitumor activity of cisplatin-loaded liposomes and nanoparticles
      in vitro].
AB  - OBJECTIVE: To compare the differences in antitumor activity between cisplatin
      (CDDP)-loaded liposomes and nanoparticles in vitro. METHODS: CDDP-gelatin
      nanoparticles (GPs-Pt) and CDDP-liposomes with similar size, zeta potential, drug
      loading efficiency and in vitro release property were prepared. The uptake in
      A549 cells and elimination kinetics were evaluated and antitumor activity was
      determined by MTT test. The internalization pathways of nanocarriers were studied
      with inhibitors. RESULTS: Internalization of two nanocarriers was clathrin and
      actin dependent. Pt accumulation delivered by GPs-Pt was significantly higher
      than that of liposomes. However, the results of kinetic analysis showed that
      liposomes had longer cellular retention, and the MRT and AUC were 3 times and
      twice of GPs-Pt, respectively. The IC(50) of liposomes was significantly lower
      than GPs-Pt. The values were 2.94+/-0.21 and 20.70+/-1.05 MUg/ml, respectively.
      CONCLUSION: Nanocarriers with similar pharmaceutical parameters can induce
      differences in cellular internalization and elimination, which influence the
      antitumor activity eventually. Compared with gelatin nanoparticle, liposome is
      preferable for cisplatin delivery.

PMID- 21845756
TI  - [Porphyrinated polyimide nanofibrous membrane for rapid detection of trace amount
      of methanol vapor].
AB  - OBJECTIVE: To prepare novel electrospun porphyrinated polyimide nanofibrous
      membrane for rapid detection of trace amount of methanol vapor. METHODS:
      Porphyrin chromophore was copolymerized into polyimide backbones and the
      porphyrinated polyimide nanofibrous membrane was prepared by electrospinning
      technique. By optimizing the processing parameters, such as solution
      concentration and electrospinning voltage, nanofibrous membrane with three
      dimensional and large surface-to-area ratio structure was fabricated for trace
      amount of methanol vapor sensing applications. RESULTS: The obtained nanofibrous
      membrane preserved typical photophysical properties of porphyrin chromophores
      with uniformly fine and smooth fiber diameter. When exposed to methanol vapor, a
      red-shift of the absorption spectra and decrease in the emission intensities was
      observed, while no significant changes were seen when the membrane contacting
      with other common alcohols. After five times of 150 ppm methanol vapor quenching
      and nitrogen gas regeneration, the fluorescence of the membrane remained
      unchanged, indicating a good reversibility. CONCLUSION: Combining the specific
      optical properties of porphyrin with large surface-area-to-volume ratio of
      nanofibrous membranes, a porphyrinated polyimide nanofibrous membrane has been
      facilely fabricated for trace methanol vapor detection. The sensing membrane
      exhibits good sensitivity, selectivity and reproducibility.

PMID- 21845757
TI  - [Association of thrombospondin-1 gene N700S polymorphism with coronary artery
      disease].
AB  - OBJECTIVE: To investigate the association of thrombospondin-1 (TSP- 1) gene
      A8831G (N700S) polymorphism with coronary artery disease (CAD). METHODS: This
      study was conducted with a case-control design including 178 patients with CAD
      (55 AMI) and 158 healthy subjects. The TSP-1 N700S polymorphism was determined by
      polymerase chain reaction and restriction fragment length polymorphism analysis.
      RESULTS: No significant difference of the AG genotype in CAD group and control
      group (1.7% compared with 0.6%, P=0.375) was detected. None of the homozygotes
      was detected for the G allele. The prevalence of the G allele was not
      significantly different between CAD group and controls (0.8% compared with 0.3%,
      P=0.376). No significant difference of the AG genotype in AMI group and control
      group (3.6% compared with 0.6%, P=0.104). The prevalence of G allele was not
      significantly different between AMI patients and controls (1.8% compared with
      0.3%, P=0.364). CONCLUSION: There are TSP-1 N700S polymorphisms in Chinese
      Zhejiang Han people, but the TSP-1 N700S variant shows a much lower prevalence
      compared with Western populations and may be not a potential risk for CAD and
      AMI.

PMID- 21845758
TI  - [Establishment of NCAM L1 minigene model and its splicing patterns in different
      cell lines].
AB  - OBJECTIVE: To establish a minigene model of neural cell adhesion molecule L1
      (NCAM L1) gene and to study its splicing patterns in different cell lines.
      METHODS: Using human genetic cDNA as template, the NCAM L1 minigene fragment was
      amplified and inserted into eukaryotic expression vector. The minigene was
      transfected into 4 cell lines and the splicing patterns of NCAM L1 minigene in
      these cell lines were studied. RESULTS: The splicing patterns of NCAM L1 minigene
      were different in individual cell lines. In PFSK and Hela cell lines, two
      splicied isoforms were generated but in COS-1 and R28 cell lines, only one
      isoform existed. CONCLUSION: NCAM L1 minigene model can be used in alternative
      splicing analysis.

PMID- 21845759
TI  - [Application of digital photography in color matching in dentistry].
AB  - OBJECTIVE: To develop a new color matching method in dentistry by application of
      digital photography. METHODS: Digital photographs were obtained of Vitapan 3D
      Master shade guide and natural teeth under the same condition, the L*a*b* values
      of each digital photography were assessed and analyzed by Photoshop CS4. RESULTS:
      The Vitapan 3D-Master shade guide was divided into 5 groups, the L* values were
      similar in each group, but decreased from group 1 to 5. The a* values of L1.5 and
      L2.5 were minimum, R1.5 and R2.5 were maximum and M1-M3 were intermediate.
      Compared with Vitapan 3D-Master shade guide, the L*a*b* values of natural teeth
      were higher. CONCLUSION: Digital photography can basically reflect the color of
      Vitapan 3D-Master shade guide, and provides a reference for color matching in
      dentistry.

PMID- 21845760
TI  - [Evaluation of different methods in determination of low level HBsAg].
AB  - OBJECTIVE: To evaluate chemiluminescent immunoassay (CLIA),
      electrochemiluminescent immunoassay (ECLIA) and ELISA in determination of low
      level HBsAg. METHODS: According to the standard of CLIA Architect i2000, 70
      samples were divided into three groups by HBsAg concentration : <1 ng/ml, 1-5
      ng/ml and >4 ng/ml. The samples were also determined by ECLIA MODULAR<E>170 and
      ELISA, and the results were compared with those measured by CLIA Architect i2000.
      RESULTS: The concordance rates of ECLIA MODULAR<E>170 with Architect i2000 was
      79.2% for <1 ng/ml group, 100% for 1-5 ng/ml group, 100% for >4 ng/ml group. And
      the concordance rates of ELISA with Architect i2000 was 0 % for <1 ng/ml group,
      45.5% for 1-5 ng/ml group and 100 % for >4 ng/ml group. CONCLUSION: For
      determination of low level HBsAg,CLIA Architect i2000 and ECLIA MODULAR<E>170
      have high credibility. ELISA is also credible when HBsAg >5 ng/ml, but not for
      low level HBsAg, especially for HBsAg <1 ng/ml.

PMID- 21845761
TI  - [Mechanism of NMDA receptor-dependent neuronal survival and neuroprotection].
AB  - NMDA (N-methyl-D-aspartate) receptors are a subtype of glutamate receptor, and
      play an important role in both synaptic transmission and synaptic plasticity.
      When excessively excited, NMDA receptors can cause cell death in many
      neuropathological scenarios such as OGD (oxygen and glucose deprivation) and
      brain injury. However, recent studies have revealed that under the physical and
      some pathological conditions, NMDA receptor could promote neuronal survival and
      protect neurons from damage.

PMID- 21845762
TI  - [Research progress on spindle assembly checkpoint gene BubR1].
AB  - BubR1 gene is a homologue of the mitotic checkpoint gene Mad3 in budding yeast
      which is highly conserved in mammalian. BubR1 protein is a key component
      mediating spindle assembly checkpoint activation. BubR1 safeguards accurate
      chromosome segregation during cell division by monitoring kinetochore-microtubule
      attachments and kinetochore tension. There is a dose-dependent effect between the
      level of BubR1 expression and the function of spindle assembly checkpoint. BubR1
      deficient would lead to mitotic progression with compromised spindle assembly
      checkpoint because cells become progressively aneuploid. Recently, it has been
      reported that BubR1 also plays important roles in meiotic, DNA damage response,
      cancer, infertility, and early aging. This review briefly summarizes the current
      progresses in studies of BubR1 function.

PMID- 21845763
TI  - [Current progress in research on epigenetic effects of air pollution].
AB  - Air pollution is associated with numerous diseases. In recent years,researches
      have increasingly showed that epigenetic modifications usually occur at the early
      stage of diseases, and make greater contributions to the occurrence and
      development of diseases compared to genetic abnormalities. Thus, researches on
      epigenetic effects of air pollution would serve for better understanding the
      interaction between air pollutants and genome in the pathogenesis of disease.
      Meanwhile, in order to reduce the exposure to air pollution and diminish the
      adverse effects related, further studies are needed to identify epigenetic
      biomarkers of air pollution so that we can take timely and effective measures in
      disease prevention.

PMID- 21845765
TI  - Carcinogenicity of radiofrequency electromagnetic fields.

PMID- 21845766
TI  - First hand: on graciousness.

PMID- 21845767
TI  - NY: Did delay in ER treatment cause injury?: Court refused to overturn $4 million
      settlement. Caruso v. Northeast Emergency Medical Associates, P.C., 2011-05598 NY
      APP 3, (6/30/2011)-NY.

PMID- 21845769
TI  - [Economic evaluation and rationale for human health risk management decisions].
AB  - The priority task of human health maintenance and improvement is risk management
      using the new economic concepts based on the assessment of potential and real
      human risks from exposure to poor environmental factors and on the estimation of
      cost-benefit and cost-effectiveness ratios. The application of economic tools to
      manage a human risk makes it possible to assess various measures both as a whole
      and their individual priority areas, to rank different scenarios in terms of
      their effectiveness, to estimate costs per unit of risk reduction and benefit
      increase (damage decrease).

PMID- 21845768
TI  - [A functional subsystem of sanitary-and-epidemiological situation surveillance of
      the unified state system for prevention and elimination of emergence situations].
AB  - Mass destructions of the social infrastructure and household systems under
      stressors in the areas of emergency situations involve marked sanitary-and
      epidemiological problems in a region's population, which in turn give rise to the
      activation of routes of transmission and formation of infectious and parasitic
      diseases. The most important lines of activities of supervising the sanitary-and
      epidemiological situation under emergencies are to timely assess the sanitary-and
      epidemiological situation, to predict, to organize, and to correct sanitary-and
      antiepidemic measures.

PMID- 21845770
TI  - [Essential hypertension as an occupational disease in engine crew members].
AB  - The paper raises the question as to whether essential hypertension should be
      included into a list of occupational diseases (intellectual, sensory, and
      emotional workloads and working conditions) in engine crew members. In the engine
      crew members of the South-Eastern Railway, the cases and days lost because of
      illness and temporary disability are higher than those in the whole railway. 32%
      of the engine drivers (assistants) are followed up for diagnosed essential
      hypertension. Hypertension (49.7%) is the main reason for suspending engine crew
      members from work as evidenced by train pre-trip medical examinations. The
      working conditions (noise, infrasound, mcroclimate) in train engineer's cabs do
      not meet the sanitary requirements; in this connection the occupational disease
      sensorineural hearing loss is also registered.

PMID- 21845771
TI  - [The factors influencing tobacco smoking in the middle school age pupils of
      Moscow].
AB  - The high prevalence of tobacco smoking among modern-day children and adolescents
      largely determines a poor prognosis of human health in future. Smoking prevention
      among children and adolescents in general educational facilities is the most
      promising measure to solve this sociomedical problem. The investigation was
      undertaken to study smoking prevalence among middle school age pupils, to
      identify the major factors contributing to their taking up smoking, and to define
      information sources and the pupils' awareness about the negative impact of
      smoking.

PMID- 21845772
TI  - [Evaluation of the mental status of high school students and its correction
      program].
AB  - Mental health indicators were studied using the cross-sectional method in
      students over 3 years of their education (2005-2008). A representative sample
      comprised 1787 first-to-third-year students from three largest high schools in
      the city. The regularities of the students' mental changes were defined during
      education: with the advancing ages of the examinees, the indicators of attention
      and logical thought increased due to the occurrence of neuroemotional imbalance
      (the emergence of depression and lower adaptation level; p < or = 0.05). A
      comprehensive target health protection program for high school students has been
      elaborated and introduced.

PMID- 21845773
TI  - [Monitoring of biological contamination of household water supply objects].
AB  - Biological contamination of environmental objects was monitored in 245 monitoring
      points of the region according to the monitoring observation program. In 2005
      2008, the proportion of drinking water samples from the distributing network of
      household water supply systems, which meet no hygienic standards, is 1.3 to 1.8%
      and the proportion of those from non-centralized water supply sources is 6.2%,
      which is due to a weak protectability of aquifers from their surface
      contamination. Comprehensive assessment of household water supply factors has
      indicated that water preparation and transportation are key links in the
      formation of household water supply problems.

PMID- 21845774
TI  - Bibliography. Nosocomial and healthcare-related infections. Current world
      literature.

PMID- 21845775
TI  - A comparative study of thin coatings of Au/Pd, Pt and Cr produced by magnetron
      sputtering for FE-SEM.
AB  - Visualization of structural details of specimens in field emission scanning
      electron microscopy (FE-SEM) requires optimal conductivity. This paper reports on
      the differences in conductive layers of Au/Pd, Pt and Cr, with a thickness of 1.5
      3.0 nm, deposited by planar magnetron sputtering devices. The coating units were
      used under standard conditions for source-substrate distance, current, HT and
      argon pressure. Carbon films, deposited by high-vacuum evaporation on small,
      freshly cleaved pieces of mica, were used as substrate and mounted on copper
      grids for TEM and SEM inspection. Au/Pd, Pt and, to a lesser extent, Cr coatings
      varied in particle density, size and shape. Au/Pd coatings have a slightly more
      granular appearance than Cr and Pt coatings, but this is strongly dependent on
      the type of sputtering device employed. In FE-SEM images there is almost no
      difference in contrast and particle size between the Au/Pd layer and the Pt
      layers of a similar thickness. The nuclei of Au/Pd are rather small with almost
      no growth to the sides or in height, making Au/Pd coatings a good alternative to
      chromium and platinum for FE-SEM of biological tissues because of its higher
      yield of secondary electrons.

PMID- 21845776
TI  - [Now the National Board of Health is sleeping again--or is it a question of
      discrimination?].

PMID- 21845777
TI  - [Comment on neurofeedback].

PMID- 21845778
TI  - [Diagnostics evaluation of periodontal diseases prevalence in the condition of
      big industrial region of Kazakhstan].

PMID- 21845779
TI  - The 5th International Conference on Bio-Inspired Models of Network, Information
      and Computing Systems (BIONETICS 2010) special track on bioinformatics.

PMID- 21845780
TI  - [Whitening process influence upon the colour of nanocomposite materials].

PMID- 21845781
TI  - Special issue on semantic descriptions of medical web resources: technologies to
      support their creation, maintenance and access.

PMID- 21845782
TI  - [Significance of neutral zone registration in the rehabilitation process of a
      patient with partial mandibulectomy: a case report].

PMID- 21845783
TI  - [Traumatic injuries of primary teeth: epidemiology, classification, approaches to
      diagnostics and treatment].

PMID- 21845784
TI  - [Root canal irrigation - component of endodontic treatment success].

PMID- 21845785
TI  - Effective date of requirement for premarket approval for three class III
      preamendments devices. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule to require the
      filing of a premarket approval application (PMA) or a notice of completion of a
      product development protocol (PDP) for the following three class III
      preamendments devices: Ventricular bypass (assist) device; pacemaker repair or
      replacement material; and female condom. The Agency has summarized its findings
      regarding the degree of risk of illness or injury designed to be eliminated or
      reduced by requiring the devices to meet the statute's approval requirements and
      the benefits to the public from the use of the devices. This action implements
      certain statutory requirements.

PMID- 21845786
TI  - [Proceedings of the 11th Scientific Conference on Tobacco, Health and Social
      Consequences, 1010, Poznan].

PMID- 21845787
TI  - [Abstracts of the Tenth Congress of the Hungarian Radiotherapy Society. Szeged,
      20-22. May 2011].

PMID- 21845788
TI  - [Proceedings of the 73rd National SIMLII Congress, 1-4 December 2010, Rome,
      Italy. Part 2].

PMID- 21845789
TI  - The effect of periodontal therapy on preterm birth and low birth weight: is the
      jury still out?

PMID- 21845790
TI  - Rural hospital charges due to ambulatory care sensitive conditions in the United
      States, by insurance type, 2000 to 2004.
AB  - In this policy brief, we estimate and document rural hospital charges due to
      ambulatory care sensitive conditions (ACSCs) in the United States, by insurance
      type, from 2000 to 2004. ACSCs are specific adverse health conditions that can be
      managed in an ambulatory setting and should not require hospitalization. Hospital
      charges due to ACSCs are reported by region and payment source (private
      insurance, Medicare, Medicaid, uninsured). Community hospitals are important
      safety-net providers, and ACSC-related hospital expenditures in those hospitals
      could reflect the consequences of uninsurance and underinsurance (inhibiting
      access to ambulatory services). Research about the trends of ACSC-related
      hospitalizations can contribute to the assessment of the access to and quality of
      primary health care systems across US regions over time. Our study used
      nationwide hospital inpatient discharge data to examine the trends and regional
      variations of rural hospital charges due to ACSCs.

PMID- 21845791
TI  - The learning files: feeding the infant and young child.

PMID- 21845792
TI  - [Tuberculosis].

PMID- 21845793
TI  - Soul man meets the blind watchmaker: C.G. Jung and neo-Darwinism.
AB  - C.G. Jung's name has recently been connected with neo-Darwinian theories. One
      major reason for this connection is that Jungian psychology is based on the
      suggestion that there exists a universal structure of the mind that has its own
      evolutionary history. On this crucial point, Jungians and neo-Darwinian
      evolutionary psychologists agree. However, it will be argued in this paper that,
      although Jungian psychology opposes the "tabula rasa" doctrine (mind as a blank
      state), Jung cannot be regarded as the founding father of evolutionary
      psychology. From the scientific perspective, Jung's biological assumptions are
      simply untenable and have been for many decades. In his attempt to fuse biology,
      spirit, and the unconscious, Jung ended in speculative flights of imagination
      that bear no resemblance to modern neo-Darwinian theories. The premise of the
      paper is that, when Jungian psychology is presented to us as a scientific
      psychology that has implications for the development of neo-Darwinian psychology,
      we should be on guard and examine the evidence.

PMID- 21845794
TI  - Depression and health related quality of life among HIV-infected people.
AB  - BACKGROUND AND OBJECTIVES: Little is known about the impact of comorbid
      psychiatric symptoms in health related quality of life (HRQL) in patients with
      HIV infection. The aim of this investigation was to describe depressive symptoms
      and the impact in HRQL in HIV infected people. MATERIALS AND METHODS: A cross
      sectional study over 150 HIV-outpatients in a tertiary hospital was designed.
      Depression data were obtained using the Beck Depression Inventory, Second Edition
      (BDI-II) inventory. HRQL data were collected by disease-specific questionnaire
      MOS-HIV. Researchers' team designed a specific template to get rest of the data.
      RESULTS: Almost three-quarters of the population were men. After adjusting for
      gender and age, HIV-related symptoms and presence of depression were found to be
      negatively associated with all the Medical Outcomes Study HIV Health Survey (MOS
      HIV) general domains and in the Physical Health Summary score and Mental Health
      Summary score. CONCLUSIONS: Optimization of HRQL is particularly important now
      that HIV is a chronic disease with the prospect of long-term survival. Quality of
      life and depression should be monitored in follow-up of HIV infected patients.
      Comorbid psychiatric conditions may serve as markers for impaired functioning and
      well-being in persons with HIV.

PMID- 21845795
TI  - Nicotine restores monoamine neurotransmitter changes in the cortex and
      hippocampus of reserpinized rats as a model of depression.
AB  - BACKGROUND AND OBJECTIVES: A number of studies have shown that nicotine has an
      antidepressant-like effect. The prevalence of smoking is much higher in people
      suffering from depression. In addition, the administration of nicotine from
      transdermal nicotine patch can exert antidepressant activity in nonsmokers and
      the continuous infusion of nicotine to rats attenuates learned helplessness, a
      putative behavioral model of depression. The aim of the present study is to
      elucidate the neurochemical effect of nicotine on monoamine levels in the
      cerebral cortex and hippocampus of reserpinized rats as a model of depression.
      MATERIALS AND METHODS: In the present study, rats were divided into control
      animals treated with saline and reserpinized group which received a daily i.p
      injection of reserpine for 15 days to establish the animal model of depression.
      Starting from the 16th day, the reserpinized rats were divided into reserpinized
      rats, and reserpinized rats treated daily with nicotine (0.4 mg/kg) for 15 and 30
      days. After decapitation, the cerebral cortex and hippocampus of each rat were
      dissected out. The levels of monoamine neurotransmitters (serotonin,
      norepinephrine and dopamine) were measured in each area using a
      spectrofluorimeter. RESULTS: The daily i.p injection of reserpine induced a
      significant decrease in monoamine levels in the cortex and hippocampus. Nicotine
      administration restored the changes in monoamine neurotransmitters induced by
      reserpine in both areas after 30 days. DISCUSSION: The data of the present study
      suggest that the antidepressant-like effect of nicotine could be mediated by the
      effect of nicotine on monoamine neurotransmitters in the cortex and hippocampus
      of rat brain.

PMID- 21845796
TI  - Buprenorphine/naloxone versus methadone in opioid dependence: a longitudinal
      survey.
AB  - BACKGROUND AND OBJECTIVES: Buprenorphine and methadone are widely used for the
      treatment of opioid dependence, but their diversion and/or misuse are frequent.
      In principle, buprenorphine/naloxone combination therapy should be associated
      with a lower frequency of drug abuse/misuse than methadone. This study assessed
      the efficacy of the substitution of buprenorphine treatment with the
      buprenorphine/naloxone combination in opioid-dependent patients. MATERIAL AND
      METHODS: 3812 drug-addicted outpatients selected from 10 Italian Public Services
      for Addiction (Ser.T.) centres in Naples (Italy) were enrolled: 3105 (81.5%) were
      treated with methadone and 707 (18.5%) with buprenorphine. The buprenorphine
      treatment was switched to buprenorphine/naloxone (4:1), and the patients were
      followed for about 1 year. The number of subjects still on treatment after 1
      year, their status according to social, educational and toxicologic (assessed by
      a urine toxicology test) parameters were assessed. RESULTS: 1 year after the
      therapy switch, the number of patients still on treatment was similarly reduced
      with methadone (2883; -7.5%) and buprenorphine/naloxone (632; -10.6%; p=0.369).
      However, in patients treated with buprenorphine/naloxone, a significant
      improvement was reported in social life status (63% versus 39% of the
      buprenorphine/naloxone and methadone treated subjects, respectively, were
      married/cohabiting p<0.001), in the educational level (43% of
      buprenorphine/naloxone treated versus 32% of the methadone treated subjects
      obtained at least a high school certificate, p<0.001) and in the toxicological
      conditions (53% of buprenorphine/naloxone treated subject versus 30% of methadone
      treated individuals had opioid- and cocaine- negative urine tests, p<0.001).
      DISCUSSION: These preliminary data suggest that buprenorphine/naloxone treatment
      of opioid dependence reduces the percentage of treated subjects similarly to
      methadone, and is associated with an improvement in social life, educational and
      toxicological conditions, compared with methadone treatment. However, we cannot
      exclude a selection bias, i.e. patients who were more likely to stabilize their
      opiate dependence switched to buprenorphine/naloxone.

PMID- 21845797
TI  - Anti-Candida albicans biofilm activity by Cassia spectabilis standardized
      methanol extract: an ultrastructural study.
AB  - BACKGROUND AND OBJECTIVE: Candida (C.) albicans infection in its biofilm mode of
      growth has taken centre point with the increasing recognition of its role in
      human infections due to the development of resistance to the commonly used
      antibiotic or phenotypic adaptation within the biofilm. Hence, in this study the
      inhibitory effect of methanol extract of Cassia (C.) spectabilis leaves was
      evaluated against biofilm forming C. albicans. MATERIALS AND METHODS: Anti-yeast
      activities were carried out using disc diffusion assay and broth dilution method
      against biofilm forming C. albicans. C. spectabilis leaves extract was assessed
      using XTT (2,3-bis [2-Methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5
      carboxanilide) reduction assay for biofilm quantification with positive control
      fluconazole. Scanning electron microscopic (SEM) and confocal scanning laser
      microscopy (CLSM) analysis further revealed reduction in C. albicans biofilm by
      C. spectabilis leaves extract. RESULTS AND DISCUSSION: The methanol extract of C.
      spectabilis showed a favorable antiyeast activity against C. albicans with MIC
      (Minimum Inhibitory Concentration) value of 6.25 mg/ml. Fluconazole and leaves
      extract showed 95.4% and 96.9% biofilm reduction respectively. The main changes
      observed under scanning electron microscopy after C. spectabilis leaves extract
      treatment were cellular damage and disruption in biofilms of C. albicans. The
      ultrastructural changes visualized by SEM were further confirmed using CLSM
      study. CONCLUSIONS: The results from this research conclusively exhibit the in
      vitro anti-biofilm potential of C. spectabilis leaves extract against Candida
      biofilm.

PMID- 21845798
TI  - Occurrence of enterotoxigenic Aeromonas species in foods of animal origin in
      North East India.
AB  - OBJECTIVE: The aim of the present study was to isolate and identify Aeromonas
      (A.) species and assess their toxin producing ability in foods of animal origin
      from North East India. MATERIALS AND METHODS: A total of 332 animal food samples
      (fish, poultry meat, pork and chevon) of which 38 (11.44%) isolates were
      identified by the 16S rRNA technique were included in the study. The
      enterotoxigenicity of the isolates was measured by the Mouse Paw Oedema Test
      (MPOT), rabbit ileal loop (RIL) and vascular permeability reaction (VPR) test.
      RESULTS: Maximum positivity was shown by the samples from fish (13.13%), followed
      by poultry meat (11.5%), pork (9.85%) and chevon (2.5%). A. hydrophila was the
      predominant species (92.10%) followed by A. sobria (5.26%) and A. caviae (2.63%).
      CONCLUSIONS: All the Aeromonas strains isolated by culture methods expressed
      enterotoxigenicity by MPOT, RIL assay and VPR test.

PMID- 21845799
TI  - Protective and curative effects of the 15 KD isolated protein from the Peganum
      harmala L. seeds against carbon tetrachloride induced oxidative stress in brain,
      tests and erythrocytes of rats.
AB  - BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the protective and
      curative effects of the 15 KD protein isolated from the seeds of Peganum harmala
      L. against carbon tetrachloride (CCl4) induced oxidative stress in rats.
      MATERIALS AND METHODS: In the protective study, animals were pretreated
      intraperitoneally with 15 KD isolated protein at doses of 4 and 8 mg/kg body
      weight as well as vitamin C (250 mg/kg body weight p.o) for 7 days and then
      challenged with CCl4 orally (1 ml/kg body weight) in olive oil (50%) for 2 days.
      In the curative study, rats were administered CCl4 orally for 2 days, then
      treated intraperitoneally with 15 KD protein (4 and 8 mg/kg body weight) and
      orally with vitamin C. RESULTS: Administration of CCl4 induced induction in
      malondialdehyde (MDA) and decrease in reduced glutathione (GSH) levels as well as
      glutathione-S-transferase (GST) activity in brain, testes and erythrocytes. The
      activity of acetylcholinesterase (AchE) in brain was also inhibited by CCl4
      administration. CONCLUSIONS: Treatment of rats either pre or post CCl4
      intoxication successfully alleviated the oxidative stress in the brain, testes
      and erythrocytes of the experimental animals. Data also showed that the isolated
      protein possessed strong antioxidant activity comparable to that of vitamin C.

PMID- 21845800
TI  - Antimicrobial and antioxidant activities of the various extracts of Verbascum
      pinetorum Boiss. O. Kuntze (Scrophulariaceae).
AB  - BACKGROUND AND OBJECTIVES: The present study was performed to evaluate the in
      vitro antimicrobial and antioxidant properties of various extracts of Verbascum
      (V.) pinetorum, a member of Scrophulariaceae family. While the antimicrobial
      activity of various extracts of V. pinetorum was determined with agar-well
      diffusion method, the antioxidant activity was examined with two complementary
      test systems, namely 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging
      and beta-carotene/linoleic acid test systems. RESULTS: The hexane extract
      exhibits antimicrobial activity against few microorganisms. However,
      dichloromethane, direct methanol and methanol/chloroform extracts are effective
      on a broad range of microorganisms. Among the tested bacteria Haemophilus
      influenzae was found to be the most sensitive bacterium. The 50% (IC50)
      inhibition activity of the methanolic extract of V. pinetorum on the free radical
      DPPH was determined as 13.04 mg/ml. In the case of the linoleic acid system,
      oxidation of linoleic acid was inhibited by methanolic extract of V. pinetorum,
      which showed 89.39% inhibition that is quite close to the value of the synthetic
      antioxidant reagent butylhydroxytoluene (BHT), 92.46%. Iridoid glycosides,
      flavonoids and saponins were determined as the major natural compounds in the
      methanolic extracts. The total phenolic components of V. pinetorum were found as
      42.45 mg/g gallic acid equivalent. CONCLUSION: The results provide evidence that
      the extracts of V. pinetorum contained iridoid glycosides, flavonoids, saponins
      and phenolic compounds which may be responsible for the substantial antimicrobial
      and antioxidant activities.

PMID- 21845801
TI  - Long dose exposure of hydrogen peroxide (H2O2) in albino rats and effect of
      Podophyllum hexandrum on oxidative stress.
AB  - OBJECTIVES: The effect of Podophyllum hexandrum methanolic extract and alpha
      tocopherol in reducing oxidative stress in male albino rats was evaluated.
      MATERIALS AND METHODS: Lipid peroxidation was monitored by measuring
      malondialdehyde (MDA) level in different tissues of rats. Activities of free
      radical scavenging enzymes (superoxide dismutase, glutathione peroxidase and
      catalase) were determined using H2O2 decomposition. RESULTS: Results showed that
      administration of H2O2 (0.1%) in drinking water of the rats, for 25 weeks,
      increased the malondialdehyde levels in liver, kidney and lung tissues of all the
      rats. However, rats receiving Podophyllum hexandrum extract and alpha-tocopherol
      had lower MDA levels in a dose dependent manner, which indicates decreased lipid
      peroxidation in these rats. Increase in the catalase activity appears to be a
      response to H2O2 accumulation. The decrease in the activity of catalase and
      increase in the activity of superoxide dismutase and glutathione peroxidase in
      different organs of the rats receiving Podophyllum hexandrum extract and alpha
      tocopherol indicates the protective effect of the plant in combating oxidative
      stress undergone by the rats. OBJECTIVES: Rhizome of Podophyllum hexandrum have
      been ethnomedically claimed to possess a wide array of biological activities
      including anticancer activity. MATERIALS AND METHODS: To verify the folklore
      claim, this study was performed in a six Human carcinoma cell lines, Lung (A
      549), Prostate (PC-3), Colon (Colo-25), Breast (MCF-7), Neuroblastoma (IMR-32)
      and CNS (SF-295) MCF-7 and MDA-MB-231. RESULTS: Methanol and 70% ethanolic
      extracts of the rhizome of Podophyllum hexandrum showed highest cytotoxic effect
      on MCF-7 (Breast) and Colo-25 (Colon) cell line, as determined with
      sulforhodamine-B (SRB) assay. CONCLUSIONS: These findings 1 - showed that
      Podophyllum hexandrum extract may ameliorate H2O2 induced oxidative stress by
      decreasing lipid peroxidation via alteration of the antioxidant defense system of
      the rats. 2 - these data also showed the anticancer activity of the plant
      extracts on different human cancer cell lines. However, further investigation is
      needed to assess the molecular mechanisms mediated anticancer activities of this
      plant.

PMID- 21845802
TI  - An in vivo and in silico approach to elucidate the tocotrienol-mediated
      fortification against infection and inflammation induced alterations in
      antioxidant defense system.
AB  - BACKGROUND: Tocotrienol (Tocomin) are naturally occurring analogues of vitamin E
      family and has been reported to possess a potent free radical scavenging
      activity. In the present study we have initially investigated protective role of
      tocotrienol against infection and inflammation induced alterations in tissues
      antioxidant defense system, as well as speculated, via in silico docking studies,
      that tocotrienol can act by directly binding to antioxidant enzymes. MATERIALS
      AND METHODS: Syrian hamsters were injected with bacterial lipopolysaccharide
      (LPS, 200 microg), zymosan (20 mg), or turpentine (0.5 ml) to mimic acute
      infection, acute systemic inflammation, and acute localized inflammation,
      respectively, which are responsible for the generation of plenty of free radicals
      that causes oxidative stress. Tocomin (10 mg) was administered daily for 10 days
      before and 12 h after lipopolysaccharides (LPS) or 24 h after turpentine or
      zymosan injection. Molecular docking studies were performed using Autodock 4.0.
      RESULTS: Our results show a significant decrease in the activities of
      antiperoxidative enzymes, glutathione reductase (GR), glutathione peroxidase
      (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione-s-transferase
      (GST), as well as reduced glutathione (GSH), in liver and kidney of LPS,
      turpentine or zymosan stressed hamsters. Feeding of 10 mg Tocomin to stressed
      hamsters was quite effective in reversing/normalizing the altered levels of
      enzymatic and nonenzymatic antioxidants in liver and kidney. In order to explore
      the interaction between tocotrienol and antioxidant enzymes a molecular docking
      study was performed. The results showed good interaction in term of binding
      energy and inhibition constant in the following order GR > CAT > SOD > GST > GPx.
      CONCLUSION: Our in vivo and in silico results for the first time indicate that
      tocotrienol significantly alleviate the condition of oxidative stress not only by
      its potent free radical scavenging properties but also may be by interacting
      directly and strongly with antioxidant enzymes as proved by molecular docking
      simulations.

PMID- 21845803
TI  - Inositol safety: clinical evidences.
AB  - Myo-inositol is a six carbon cyclitol that contains five equatorial and one axial
      hydroxyl groups. Myo-inositol has been classified as an insulin sensitizing agent
      and it is commonly used in the treatment of the Polycystic Ovary Syndrome (PCOS).
      However, despite its wide clinical use, there is still scarce information on the
      myo-inositol safety and/or side effects. The aim of the present review was to
      summarize and discuss available data on the myo-inositol safety both in non
      clinical and clinical settings. The main outcome was that only the highest dose
      of myo-inositol (12 g/day) induced mild gastrointestinal side effects such as
      nausea, flatus and diarrhea. The severity of side effects did not increase with
      the dosage.

PMID- 21845804
TI  - Factors influencing quality of life after total laryngectomy: a study of 92
      patients.
AB  - BACKGROUND AND OBJECTIVES: Total laryngectomy is a radical surgery for advanced
      laryngeal cancer. In the present study we evaluate the influencing factors for
      long term quality of life of 92 laryngectomees. PATIENTS AND METHODS: 92 patients
      who underwent laryngectomy for laryngeal cancer in the University Hospital of
      Patras, Greece were evaluated using a modified version of the EORTC-QOL-C30
      questionnaire. The patients were distributed into 6 groups based on time elapsed
      between surgical treatment and completion of the questionnaire, ranging from 2
      years for group 1 to 9-10 years for group 6. RESULTS: The mean value of
      psychological status (p=0.01), smelling disorders (p=0.032), mood change
      (p=0.003) were statistically significant in regard to the patient's overall view
      of their life postsurgically. Coexisting illness (defined as diabetes,
      hypertension or prostate disease which required medication on daily basis or
      hospitalization more than two times a year) was also significantly affecting
      (p=0.021) the patient's oral communication skills. CONCLUSION: Quality of life is
      affected by functional disabilities and the psychological state of the patients.
      No statistically significant improvement over time was noted in our series.

PMID- 21845805
TI  - Ketoprofen 2.5% gel: a clinical overview.
AB  - Ketoprofen (KP), a nonsteroidal anti-inflammatory drug (NSAID), possesses
      analgesic, antipyretic and anti-inflammatory properties. Oral KP is widely used
      in musculoskeletal pain and inflammation in muscles and joints, including
      arthritis pain, osteoarthritis, stiffness of the joints, soft tissue rheumatism,
      and sports injuries. In common with all NSAIDs, oral KP has been associated with
      systemic adverse events and in particular gastrointestinal disorders. Topical
      application of the active ingredient is locally effective and at the same time
      minimises the risk of systemic adverse events. Pharmacokinetic studies show that
      serum levels of the active ingredient following topical KP 2.5% gel are less than
      1% of those reported after oral dosing, thereby providing good levels of pain
      relief without the systemic adverse events normally associated with oral NSAIDs.
      In comparative studies, topical KP 2.5% gel twice daily showed clinical benefits
      in patients with a range of musculoskeletal conditions. KP 2.5% gel is generally
      well tolerated but the treated skin area should not be exposed to direct
      sunlight, including solarium (sunbeds), during the treatment and for 2 weeks
      afterwards as topical photosensitization has been reported. To our knowledge,
      this is the first overview on the use of topical KP (tKP) 2.5% gel which includes
      data from both clinical trials and from 'real-life' clinical practice.

PMID- 21845806
TI  - Update on low molecular weight heparins at the beginning of third millennium.
      Focus on reviparin.
AB  - BACKGROUND: This review provides an outline of the main pharmacological and
      clinical features of low molecular weight heparins (LMWHs) and a wider
      description of reviparin. The basic pharmacological properties of LMWHs are
      compared with those of unfractionated heparin, showing clear advantages of the
      former, mainly as for pharmacokinetic profile. DESIGN: Consequently LMWHs are
      characterized by a more predictable behaviour. A key issue is the lack of
      "bioequivalence": LMWHs are in fact distinct chemical entities, with typical
      pharmacological and clinical profile for each agent. Therefore, they are not
      reciprocally interchangeable. The efficacy and safety of reviparin, a second
      generation LMWH, has been evaluated in many clinical trials as both thrombosis
      prevention and treatment. Reviparin use is documented in general and orthopaedic
      surgery. In patients undergoing abdominal surgery reviparin resulted more
      effective and better tolerated than unfractionated heparin (UFH). In total hip
      replacement patients, reviparin compared favourably with enoxaparin, showing the
      same efficacy but better safety. In patients who undergone total hip replacement,
      also the long-term, out of hospital prevention of deep vein thrombosis (DVT) has
      been proven. CONCLUSIONS: The comparison with acenocoumarol demonstrated that
      reviparin was more effective in preventing DVT recurrences and far better
      tolerated than oral anticoagulant treatment. Reviparin was also effective and
      well tolerated in immobilised patients following leg injury with plaster casts or
      braces applications. Positive results were also obtained in the treatment of
      venous thromboembolism in well-designed studies on large patient populations. In
      this indication reviparin compared favourably with iv UFH. As for the use in
      cardiology patient, reviparin is at present the only approved LMWH for the
      prevention of acute thrombotic events in patients undergoing percutaneous
      transluminal coronary angioplasty.

PMID- 21845807
TI  - Use of macrogol 4000 in chronic constipation.
AB  - BACKGROUND: Chronic constipation is a common functional disorder of the
      gastrointestinal tract, affecting up to 35% of the general population, and
      especially the elderly. However, its definition as perceived by the patient can
      vary, making it difficult to understand the problem and find appropriate
      therapeutic measures. The approach to chronic constipation, thus, needs a
      thorough understanding of the patient's complaint and the main pathophysiological
      mechanism requiring treatment. Lifestyle changes do not usually meet with
      complete patient satisfaction. Other treatments include different types of
      laxatives. Of these, osmotic laxatives appear one of the most effective and are,
      therefore, frequently prescribed. DESIGN: This review will cover the topic of
      osmotic laxatives, specifically focusing on polyethylene glycol (PEG/macrogol
      4000) in chronic constipation and as a key agent for bowel cleansing prior to
      colonoscopy. PEG formulations, including macrogol 4000, are safe, effective
      treatments for constipation, even in children and elderly patients. Macrogol 4000
      may well be more palatable than combined formulations (macrogol 3350 with
      electrolytes), which could help improve adherence to the long-term treatment
      required for chronic constipation. CONCLUSIONS: PEG/macrogol is also recommended
      as an effective option for bowel cleansing prior to colonoscopy. The improved
      cost-effectiveness of macrogol over other commonly prescribed laxatives, such as
      lactulose, should be taken into consideration.

PMID- 21845808
TI  - Selective lymphadenectomy for penile cancer.
AB  - INTRODUCTION: Lymph node treatment in patients with penile cancer has been longly
      debated in the last 15 years, with surgeons advocating therapeutic
      lymphadenectomy and others advocating selective lymphadenectomy (SLND). MATERIALS
      AND METHODS: We evaluated the outcome of clinically node negative penile cancer
      patients treated with SLND. Since March 2000, 35 node negative penile cancer
      patients were operated on mainly at the Division of Plastic Surgery, San
      Gallicano Institute, Rome (Italy), with SLND. RESULTS: A sentinel node was
      detected in 34 out of 35 patients (42 groins). With a minimum of five years
      follow up, metastases were noted in 5 out of 35 patients. Out of the remaining 30
      patients, 2 developed node metastases in the operated inguinal region (6.6%).
      DISCUSSION: SLND for penile cancer compared to surveillance only greatly improves
      survival rate and disease-free rate (91% vs 79% after 3 years follow-up).
      Identification of more specific markers for SCC lymph node metastases will make
      the false negative-rate drop further.

PMID- 21845809
TI  - Primer malignant melanoma of kidney: a case report.
AB  - We report a case of malignant melanoma of the kidney presenting as a primary
      tumor. This tumor was found incidentally in a 67-year-old man. This is a rare
      primer malign melanoma case of the kidney in 67-year old man, with no history of
      melanoma, presenting with an asymptomatic solitary renal mass. The patient
      underwent a right radical nephrectomy, We discuss the probability that this tumor
      is renal in origin and directly linked to the origin of malignant melanoma.

PMID- 21845810
TI  - Passive smoking and respiratory allergies in adolescents.
AB  - OBJECTIVE: The aim of our study was to investigate impact of active and passive
      smoking on total and specific serum IgE levels and on incidence of developing
      allergic diseases (i.e. asthma, rhinitis) in a group of Croatian adolescents.
      METHODS: Our study consisted of random sample of one hundred fifty-five (155)
      voluntary pupils (80 males and 75 females), with mean age of 16.72 +/- 1.25
      years, from one high school in the city of Varazdin (north-west part of Croatia).
      Their smoking habits were examined by interview administered by a single trained
      survey worker while diagnosis of allergic disease (i.e. asthma and allergic
      rhinits) had to be previously confirmed by physician. Total and specific serum
      IgE levels were determined using enzyme-linked immunosorbent assay (ELISA) method
      in Central Laboratory of Clinic for lung diseases Jordanovac, Zagreb (Croatia).
      RESULTS: Statistically significant higher prevalence of allergic diseases was
      found in the group of passive smokers as opposed to nonsmokers (chi2=9.29,
      p=0.002) as well as in active smokers compared to nonsmokers (chi2=4.45,
      p=0.034). Also, total IgE (IU/ml) was significantly higher in passive smokers
      when compared to non-smokers (t=13.039, p<0.01), and in passive smokers as
      opposed to active smokers as well (t=4.960, p<0.01), while difference in its
      level between active smokers and non-smokers was not statistically significant.
      The level of specific IgE to Dermatophagoides pteronyssinus between active
      smokers, passive smokers and non-smokers resulted to be not statistically
      significant. CONCLUSIONS: Results of the study indicate that clinical
      manifestations of allergic diseases are more frequent in smokers (both active and
      passive) than in nonsmokers. Our investigation leads us to a presumption of a
      possibly more harmful effect of passive than active smoking in the adolescent
      high school population. Statistically highest IgE level in passive smokers as
      opposed to non-smokers or smokers could be attributed to longer duration of
      exposure to tobacco smoke in passive smokers and tobacco's potential cumulative
      effect on allergic senzitisa-tion, although investigations with more precised and
      detailed mesures including higher number of participants are warranted.

PMID- 21845811
TI  - Huge expanding extrapleural haematoma in a coronary artery disease patient:
      conservative or surgical treatment?

PMID- 21845812
TI  - Segmental tuberous sclerosis in a patient presenting as unilateral facial
      angiofibromas, periungual fibromas and Shagreen patch.
AB  - Tuberous sclerosis (TS) known as Epiloia and Bourneville's disease is an
      autosomal dominant inherited disorder that can affect many organ systems.
      Tuberous sclerosis has many forms of clinical presentation. Rarely, multiple
      facial angiofibromas of unilateral distribution have been reported. We describe a
      patient with unilateral facial angiofibromas, periungual fibromas and Shagreen
      patch.

PMID- 21845813
TI  - Endodontic quality: at what cost.

PMID- 21845814
TI  - The new role for hygienists in modern practices.

PMID- 21845815
TI  - Oral medicine and the teenage patient.

PMID- 21845816
TI  - Irrigation: when to use what.

PMID- 21845817
TI  - Ultra-thin veneers: beautiful and natural.

PMID- 21845818
TI  - Considerations when restoring a nonvital tooth.

PMID- 21845819
TI  - T-scan dental force analysis for routine dental examination.

PMID- 21845820
TI  - Improving aesthetics in a narrow jaw with composite, Part 2.

PMID- 21845821
TI  - Midfacial development in adult obstructive sleep apnea.

PMID- 21845822
TI  - Intraoral repair of a zirconia-based restoration.

PMID- 21845823
TI  - [Bacteriology of ethmoidal sinus in chronic rhinosinusitis with and without nasal
      polyps].
AB  - OBJECTIVE: To compare the bacteriologic features of anterior ethmoidal biopsy
      specimens between chronic rhinosinusitis without nasal polyps (CRSNP-), chronic
      rhinosinusitis with nasal polyps(CRSNP+) and control patients. METHOD: The biopsy
      specimens obtained during the nasal endoscopic surgery were cultured for aerobic
      and anaerobic bacteria. RESULT: One hundred and nineteen biopsy specimens were
      processed for homogenization and semiquantitatively bacterial culture of aerobe
      and anaerobe. Bacterial culture were positive in 104 specimens (total culture
      positive rate was 87.4%). The positive rate of aerobe or facultative anaerobe
      culture were 86.5%, 85.7%, 90.0% in CRSNP- group, CRSNP+ group and control group,
      respectively. There were no significant differences between 3 groups (P > 0.05).
      Mixed growth of aerobe and anaerobe bacteria were mainly detected in the biopsy
      specimens and the positive rate were 78.4%, 81.0% and 85.0% in CRSNP- group,
      CRSNP+ group and control group. There were no significant differences in 3 groups
      (P > 0.05). The most common aerobe bacteria found in 3 groups were coagulase
      negative staphylococci and corynebacterium species and there were no significant
      differences between 3 groups (P > 0.05). The positive rate of anaerobic bacteria
      culture were 78.4%,76.2% and 77.5% in 3 groups. There were no significant
      differences between the groups (P > 0.05). Propionibacterium and
      peptostreptococcus species were the most common anaerobes, and there were no
      significant differences between 3 groups (P > 0.05). CONCLUSION: There are no
      significant differences in the bacteriologic features of ethmoidal biopsy
      specimens between CRSNP+, CRSNP- and control patients. Therefore, bacterial
      infection may not play a key role in the pathogenesis of nasal polyps in CRS
      patients.

PMID- 21845824
TI  - [Relationship between nasal obstruction symptoms and objective parameters of
      acoustic rhinometry].
AB  - OBJECTIVE: To investigate the relationship between the subjective sensation of
      nasal obstruction and the corresponding objective parameters of acoustic
      rhinometry. METHOD: Three hundred and sixty-five patients with nasal diseases
      were divided into two groups: one group included 220 cases with nasal
      obstruction, and the second group of 145 cases without nasal obstruction. Seventy
      healthy adults were selected as control. Each one were assessed for nasal minimal
      cross-sectional area (NMCA), volume of nasal cavity (NV), nasal airway resistance
      (NAR) and distance of the minimal cross section area from the nostril (DCAN) by
      using acoustic rhinometry, and the subjective test were performed using the VAS
      scores. The results were statistically analyzed. RESULT: NV, DCAN and NAR had a
      significant difference between nasal obstruct group and control group (P < 0.05).
      The VAS score had linear correlation with NMCA, NV, DCAN and NAR, and the
      correlation coefficient were R(NAR) = 0.7385, R(NV) = -0.853 2, R(NMCA) = -0.745
      4 and R(DCAN) = 0.369 7, respectively. CONCLUSION: Since NAR and NV coincide with
      the subjective perception of patients with nasal obstruction, they can be used as
      the sensitive parameters to evaluate subjective symptoms of patients.

PMID- 21845825
TI  - [Treatment of maxillary cyst with endoscopic fenestration in nasal bottom].
AB  - OBJECTIVE: To explore the feasibility of treatment of maxillary cyst with only
      fenestration in nasal bottom by nasal endoscope. METHOD: Eighteen patients with
      maxillary cyst manifested with facial swelling or hard palate bulging were
      diagnosed by CT scan and needle aspiration biopsy, and then underwent cystic
      fenestration operations with the tooth in cyst kept intact. RESULT: After over 2
      years follow-up with endoscope (partly CT scanned), recurrent infection was not
      noticed in all cases, contour of maxilla was well preserved with ostium patent
      and cystic cavity markedly shrinks. CONCLUSION: Endoscopic fenestration in nasal
      bottom only is a safe, reliable, and effective procedure in the treatment of
      maxillary cyst.

PMID- 21845826
TI  - [Prevalence of allergens for Changsha patients with allergic rhinitis].
AB  - OBJECTIVE: To investigate the allergens in patients with allergic rhinitis, to
      find common allergens of Changsha and to provide statistic basis for a reasonable
      prevention and treatment. METHOD: The allergens in 1437 patients with allergic
      rhinitis in Changsha were detected by skin prick test. RESULT: Eight hundred and
      ninety-eight (62.49%)of 1437 cases presented positive reaction. Among positive
      cases in inhalation group, the most common allergen was flour mite (98.33%), then
      were house dust mite (94.54%), mycetes II (19.27%) and weed (18.37%). Shrimp
      (35.41%) was the most common allergens in food group. And in childhood,
      adolescence and adulthood prick-positive cases, the ratio of more than 2 positive
      allergens were about 8.57%,18.04%, 19.15%. CONCLUSION: The study shows that the
      flour mite and house dust mite are the most common allergens in Changsha.

PMID- 21845827
TI  - [Endoscopic sinus surgery for multi-structural abnormality in nasal cavity].
AB  - OBJECTIVE: To evaluate the indications and effects of endoscopic surgery for
      patients with multi-structural abnormality in nasal cavity. METHOD: Endoscopic
      surgery were used in management of 304 patients with multi-abnormal anatomy with
      nasal septoplasty, middle and inferior turbinatoplasty, ethmoidectomy and so on.
      RESULT: The patients were followed up for six months or more and no post
      operative complications were found. Of 304 patients, 278 cases were cured, 23
      cases improved and 3 cases ineffective. Total effective rate was 99.0%.
      CONCLUSION: According to the specific lesion situation, it is able to obtain a
      satisfactory cure rate with treatment on multi-structural abnormality by
      endoscopic surgery and post-operative nasal lavage in the principle of minimal
      invasion and retaining mucosal function.

PMID- 21845828
TI  - [Expression of microtubule-associated protein 1 light chain 3 in laryngeal
      carcinoma].
AB  - OBJECTIVE: To investigate the expression of microtuble-associated protein 1 light
      chain 3 (LC3) in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression
      of LC3 in 50 cases of LSCC, 45 cases of para-carcinoma, 10 cases of laryngeal
      papilloma and 16 cases of polyp of vocal cord were detected by
      immunohistochemistry (MaxVision method). Expression level of LC3 mRNA was assayed
      by RT-PCR in 41 of LSCC, 41 of para-carcinoma tissue and 11 of polyp of vocal
      cord. RESULT: The positive rates of LC3 protein expression were 60.0%, 93.3%,
      90.0%, 93.8% in LSCC tissue, para-carcinoma, laryngeal papilloma and poly of
      vocal card tissues, respectively. The positive rates of LC3 were significantly
      lower in LSCC than in para-carcinoma and poly of vocal cord (chi2 = 18.135, P <
      0.01). The mRNA levels of LC3 were significantly lower in LSCC than in para
      carcinoma and poly of vocal cord (0.57 +/- 0.08 )vs (0.99 +/- 0.11) and (1.07 +/-
      0.05) , F = -255.872, P < 0.01. The expression of LC3 were related to tumor
      location and pathological grade (P < 0.05), but not related to age, T stage,
      clinical stage and lymphoid metastasis (P > 0.05). CONCLUSION: Expression of LC3
      are down-regulated in LSCC. The change of autophagic capacity may play an
      important role in occurrence and development of LSCC.

PMID- 21845829
TI  - [Expression of CK19 mRNA and EGFR mRNA in the peripheral blood and its
      relationship with lymphatic metastasis in laryngeal carcinoma model].
AB  - OBJECTIVE: To explore clinical evaluate of CK19 mRNA and EGFR mRNA for diagnosis
      of laryngeal carcinoma micrometastasis, correlation between circulation tumor
      cell and lymph node metastasis. METHOD: Of 30 nude mice, 25 were randomly divided
      into 5 experimental groups (5 mice in each group), 5 were acted as control group.
      The mice were killed 2,4,6,8 and 10 weeks after injection. The expression of CK19
      and EGFR mRNA in the peripheral blood and tumor tissue were detected by RT-PCR
      assay. The expression of EGFR in tumor tissue were detected by
      immunohistochemistry and lymph node transfer were confirmed using continuous
      pathological dying. RESULT: None of CK19 and EGFR mRNA were detected in
      peripheral blood of control group, CK19 mRNA-positive rate was 48% and 80% in
      peripheral blood and tumor tissue from the experimental group, respectively, and
      EGFR mRNA-positive rate was 36% and 76%, respectively. Lymph node metastasis
      happened in the exponential growth phase and transfer rate was 60%(15/25). The
      expression of CK19 mRNA and EGFR mRNA in lymphatic metastasis groups was higher
      than that of control, with a positive correlation between lymphatic metastasis
      and CTC (r = 0.655 , P < 0.01). The protein positive expression rate of EGFR were
      88%(22/25) in tumor tissue. All peripheral blood expressed EGFR concomitant EGFR
      expressing in tumor tissues, and a high expression of EGFR in tumor tissue
      displayed high expression of EGFR in peripheral blood as well. CONCLUSION: The
      expression of CK19 and EGFR mRNA in the peripheral blood can provide predictive
      information of lymphatic metastasis, EGFR mRNA might be a new target of treatment
      and diagnosis for malignant tumour.

PMID- 21845830
TI  - [Experimental study on the impact of urban inhalable particles on allergic
      rhinitis of rats].
AB  - OBJECTIVE: In order to study the effect of inhalable particles on provocation of
      rat allergic rhinitis model and its possible mechanism. METHOD: After basic
      sensitizing the experimental rats with OVA by intraperitoneal injection, three
      groups were provocated by solo OVA, PM10+OVA and solo PM10 through nasal cavity
      respectively. The control group was sensitized by NS instead of OVA, and then
      provocated by NS as the method of experimental groups. The symptoms of rat during
      the provocation were observed and recorded. Then, the rats were sacrificed 24
      hours after the last provocation, and the expression of IL-4 in nasal mucosa were
      detected by immunohistochemical method. RESULT: The groups of OVA and PM10+OVA
      both had provocated the obvious symptoms of allergic rhinitis, while the groups
      of PM10 and NS had the symptoms of scratching nose occasionally. By statistical
      analysis of the amount of IL-4 positive cells, there were significant differences
      between each experimental group and NS group, and there was significant
      difference between three experimental groups. The amount of IL-4 positive cells
      in PM10+OVA group was obviously higher than that in other groups. CONCLUSION: In
      the period of provocation the rat allergic rhinitis, the inhalable particles play
      a synergic role with allergen, and it can aggravate the symptoms of allergic
      rhinitis.

PMID- 21845831
TI  - [Preface for special issue on biological products].
AB  - Biological products are a kind of special agents for the prevention, diagnosis,
      and treatment of diseases. The research and development of biological products
      come from the combined knowledge of many subjects, such as microbiology,
      immunology, molecular biology, cytology, genetic engineering and fermentation
      technology. Biological products industry is the core and the hot spot of the
      biotechnology industry. In recent years, China has made some advances in
      biological products research and development. To promote biological products
      research in China, invited reviews and selected research articles were published
      in this special issue of "Biological Products". The reviews and research articles
      focus on the field of the biological products for the prevention, diagnosis, and
      treatment of disease.

PMID- 21845832
TI  - [Fish interferon response and its molecular regulation: a review].
AB  - Interferon response is the first line of host defense against virus infection.
      Recent years have witnessed tremendous progress in understanding of fish innate
      response to virus infection, especially in fish interferon antiviral response. A
      line of fish genes involved in interferon antiviral response have been identified
      and functional studies further reveal that fish possess an IFN antiviral system
      similar to mammals. However, fish virus-induced interferon genes contain introns
      similar to mammalian type III interferon genes although they encode proteins
      similar to type I interferons, which makes it hard to understand the evolution of
      vertebrate interferon genes directly resulting in a debate on nomenclature of
      fish interferon genes. Actually, fish display some unique mechanisms underlying
      interferon antiviral response. This review documents the recent progress on fish
      interferon response and its molecular mechanism.

PMID- 21845833
TI  - [Application of multi-copies in expression of smaller peptides: a review].
AB  - The technology of genetic engineering has been widely used to express
      macromolecules such as enzymes. However, it is difficult to detect and purify the
      micromolecules such as small peptides, because of their instability and
      degradability. Construction of multi-copy recombinant expression plasmid can be
      achieved by inserting multiple target genes or expression cassette containing
      target genes with the same orientation into expression vector. This is effective
      to increase the expression level of small peptides. In this article we described
      four methods in order to provide some optional methods and ideas for the
      expression of active small peptides.

PMID- 21845834
TI  - [Genesis, development and application prospect of antibody library: a review].
AB  - Antibodies are immunoglobulins specifically introduced by immunity response of
      high animals, with the responsibility for recognising and cleaning out specific
      antigens. Antibody is not only a powerful weapon against pathogen invasion in the
      organism, but also a tool for specific molecular recognition used in basic
      scientific research. The diversity of antibody molecules resulted in the concept
      of antibody library; each individual animal is a natural antibody library. In the
      post-genome era, in order to fit various "omics", especially for proteomics
      requirement of high throughput technology, some gene engineering antibody
      libraries and antibody alternative libraries have been constructed based on phage
      display technology. Yet, more and more in vitro display systems such as ribosome
      display, mRNA display have been used for antibody library study, and that present
      more advantages than phage display. This mini review outlines the genesis,
      development and application prospect of antibody libraries according to the
      published reviews and research articles, and offers up to date development and
      application prospect of antibody library technology.

PMID- 21845835
TI  - [Aptamers: characteristics and applications in pathogenic microorganism].
AB  - Aptamers are a group of artificial oligonucleotides identified by exponential
      enrichment system evolution technology (Selective expansion of ligands by
      exponential enrichment, SELEX). Aptamers have been widely used in basic research,
      clinical diagnostics, and nano-technology. In this article we will introduce the
      technology of aptamer and summarize its applications in medical microbiology.

PMID- 21845836
TI  - [Overview of Gp96 mediated immunity].
AB  - As a member of the HSP90 family, heat shock protein (HSP) Gp96 is one of the most
      abundant proteins in the endoplasmic reticulum (ER), which displayed important
      molecular chaperones function in cells. Gp96 can stimulate the production of
      cytokines by activating the antigen presentation cells (such as dendritic cell,
      et al) in innate immunity. It is capable of eliciting an antigen-specific
      cytotoxic T lymphocyte (CTL) immune response to eliminate pathogens and tumors by
      facilitating antigen cross-presentation in adaptive immunity. Gp96 is also an
      ideal adjuvant in many recent researches. Here, we review the progress that
      addresses the role of biological characteristics, immunogenic mechanism that may
      be involved in the induction of anti-infection immune response and antitumor
      immunity, which may guide the new vaccine strategies with the knowledge of Gp96
      antigen complexes.

PMID- 21845837
TI  - [Mechanism of intravenous immunoglobulin therapy for severe hand-foot-mouth
      disease: a review].
AB  - Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by various
      enteroviruses. Recently, large HFMD outbreaks caused by enterovirus type 71
      (EV71) have been frequently reported in China, posing great threats on children's
      health. There is no specific antiviral therapy for severe HFMD, and patient
      management mainly depends on supportive and symptomatic treatment. Intravenous
      immunoglobulin (IVIG) is a pharmaceutical preparation of human IgG that is pooled
      from thousands of healthy blood donors, and contained neutralization antibodies
      against various enteroviruses, including EV71. IVIG therapy should be carefully
      administrated for severe HFMD considering its role on passive immunization
      against EV71 and immune regulation.

PMID- 21845838
TI  - [Recombinant adeno-associated virus vector related impurities].
AB  - Recombinant adeno-associated virus (rAAV)-based vectors that can stably express
      therapeutic genes in vivo without detectable side-effect have shown great promise
      for human gene therapy. A major challenge for translation of promising research
      to clinical development is how to establish clinically compatible purification
      methods in separating rAAV from potentially pathogenic impurities, especially
      rAAV vector-related impurities, a class of impurities corresponding to AAV
      particles that closely resemble bona fide vectors and are difficult to remove. In
      this review we summarize the assembly process of rAAV vector-related impurities
      and their characteristics differed with rAAV vectors, and evaluate several
      current technologies to prevent their formation or separate them from rAAV
      stocks.

PMID- 21845839
TI  - [Current views on rare diseases research and orphan drugs development].
AB  - Interest in rare diseases research and orphan drugs development has been
      increased distinctly in recent years. The number of affected people with rare
      diseases is considerable around the world and the formulation of national and
      international incentive policies to accelerate orphan drugs development, aiming
      at offering facilities and necessary conditions for patient access to treatment,
      gains favorable results. In particular, more measures should be taken to catalyze
      further progress due to behindhand level in this field in China. Additionally,
      therapeutic methods of rare diseases were also discussed.

PMID- 21845840
TI  - [Current status and trends in blood biologicals].
AB  - Blood products are those biologicals derived from plasma or obtained by
      recombinant technologies. This overview covers the characteristics and
      classification of plasma proteins, the current status of products (albumin,
      immunoglobulins, coagulation factors and microcontent proteins), as well as the
      likely trends in the near future. Human serum albumin is one of the earliest,
      safest and most widely used proteins in the pharmaceutical field. The approval
      and development of high-purity plasma albumin, recombinant human albumin and HSA
      fusion proteins provide a favorable prospect for the therapeutic protein. Normal
      immunoglobulin contains antibodies to all the micro-organisms prevalent in the
      donor population. The IMIG is relatively simple to prepare and use, and the side
      effects are acceptable; IVIG is used mainly to treat patients with primary
      immunodeficiency syndromes; SCIG preparations can be used in selecting suitable
      patients for home therapy and have occurred fewer adverse systemic reactions;
      specific immunoglobulins contain concentrations of antibody to an individual
      organism or toxin at a higher titer than normal immunoglobulin and can not be
      replaced in clinical use. The plasma-derived or recombinant coagulation factors
      are used to treat the patients with congenital or acquired factor deficiency. The
      products such as Fibrinogen, FVII, FVIII, von Willebrand complex, FIX/PCC, FXI,
      FXIII and so on, have been widely used and proved to be effective. The
      development of recombinant FVIIa is now as a good bypassing product to
      haemophilia with inhibitors. The Fibrinogen and thrombin play a very important
      role in surgery hemostasis. Moreover, microcontent proteins including protein C,
      antithrombin, alpha 1-AT, tPA have been licensed and used in clinical treatment;
      a number of other small field proteins are under produced research or pre
      clinical investment. The ongoing development of new recombinant plasma proteins
      is providing alternatives for patients, but the distinct position and the
      potential impact of plasma-derived preparations are unique, furthermore the
      development of new plasma protein is still a hot spot in global pharmaceutics.
      Nowadays, a relative difference exists in the development of blood products
      between our nation and developed countries, so the domestic manufacturers are
      faced with chances and challenges.

PMID- 21845841
TI  - [Establishment of a stable and inducible mammalian cell line expressing influenza
      virus A M2 protein].
AB  - Matrix protein 2(M2) is an integral tetrameric membrane protein of influenza A
      virus, which functions as ion channel. M2 sequence has shown remarkable
      conservation, so there has been growing interest in it as "universal" vaccine. In
      order to establish a stable 293 cell line that express M2 protein under the
      control of the tetracycline operator, M2 gene was obtained by PCR amplification
      from the plasmid containing the segment 7 of influenza A virus strain A/PR/8/34
      firstly. The PCR product was cloned into BamH I/Not I restriction site of
      pcDNA5/FRT/TO vector, and cotransfected with pOG44 which express Flp recombinase
      into Flp-In T-REx-293 cell. Integration of pcDNA5/FRT/TO-M2 into the cell genome
      at the Flp Recombination Target (FRT) site brought the SV40 promoter and the
      initiation codon in frame with the hygromycin resistance gene. Thus, stable cell
      lines were selected for hygromycin resistance. The expression of M2 protein from
      hygromycin-resistant cell was induced by addition of tetracycline into the cell
      culture media, and then tested by indirect immunofluorescence assay (IFA). 16
      strains with high expression of M2 were selected. After subculturing for more
      than ten passages, the cell lines still stably expressed M2 protein. No M2
      protein could be detected without tetracycline induction, suggesting that the
      expression was strictly controlled by tetracycline operator. The cell lines
      expressing M2 will be useful for further functional studies of M2 protein,
      detection of immune response against natural structure M2 protein and development
      of live attenuated influenza virus vaccine with reverse genetics technique.

PMID- 21845842
TI  - [Constructing a phage-displayed random mutation library of HIV-1 Tat38-61 at the
      sites of 51 and 55 amino acids in basic region].
AB  - We constructed a phage-displayed random mutation library of Tat38-61(51N/55N),
      for studying the molecular evolution screening of HIV-1 Tat38-61 epitope. We used
      primers containing the random nucleotide sequences, and introduced the random
      mutations at the sites of 51 and 55 amino acids coding sequences into full-length
      Tat sequences by overlapping PCR. With the randomly mutated full-length Tat as
      template, the Tat38-61(51N/55N) mutants which contained recognition sequences for
      the Xba I in both ends were amplified by PCR using the designed primers. The
      mutants were cloned into Xba I site in the phagemid vector pCANTAB5S, then the
      recombinants were transformed into E. coli TG1, a phage-displayed the random
      mutation library of Tat38-61(51N/55N) was constructed by the rescue of help virus
      M13KO7. The results showed that the library consisted of about 5.0 x 10(6)
      colonies and the phage library titer was 2.65 x 10(12) TU/mL. More than 56.50%
      colonies in the library were positive for insertion. Sequence analysis showed
      that the nucleotides encoding amino acids at the sites of 51 and 55 distributed
      randomly. The constructed mutation library could meet the requirements for the
      following molecular evolution screening, and might prepare the Tat mutants for
      the further study of new Tat vaccine candidates.

PMID- 21845843
TI  - [Purification and characterization of a kringle-deficit mutant of human
      plasminogen with Arg-Gly-Asp tripeptide expressed in Pichia pastorsis].
AB  - To obtain a recombinant human plasminogen (hPLG) with potential anti-platelet
      aggregation activity, we cloned the cDNA coding Pro544 to Asn791 of hPLG, a
      kringle-deficit derivative (hPLG-deltaK). The Pro559 in activation loop was then
      mutated into Asp559 to provide Arg-Gly-Asp (RGD) motif. The constructed
      pPICZalphaA-RGD-HPLG-deltaK plasmid was expressed in yeast Pichia pastoris GS115,
      which produced RGD-hPLG-deltaK about 0.160 g/L broth. After affinity
      chromatography, the purity of the recombinant protein reached above 90%. Western
      blotting test confirmed that it retained the immunological reaction capability as
      human PLG. Its urokinase activation rate in 24 hours and its fibrinolytic
      activity made no deference against native hPLG-deltaK (P=0.630, n=5).
      Importantly, after activation by urokinase, RGD-hPLG-deltaK showed a
      significantly higher platelet aggregation inhibition rate (Ri) (21.8% +/- 1.57%)
      than hPLG-deltaK (3.8% +/- 0.33%) (P=0.000, n=5). These results proved that we
      constructed an hPLG mutant with anti-platelet aggregation activity, which made a
      foundation for developing innovative thrombolytic drugs with multifunction.

PMID- 21845844
TI  - [Immunological efficiency induced by HIV-1 p24 DNA combined with P24 protein].
AB  - New strategies to improve vaccine efficacy against human immunodeficiency virus
      type 1 (HIV-1) are still required. DNA vaccines, exhibiting potential advantages
      over conventional vaccines for their simplicity and versatility, can induce
      specific humoral and cellular immune responses. We developed a recombinant pVAX1
      DNA vector carrying p24 gene of HIV-1. The results showed that pVAX1 mediated
      gene possessed the ability of effective expression in both transfected 293T cells
      and BALB/c mice. And pVAX1-p24 DNA prime and boost immunization can induce
      significant P24-specific humoral immune responses and cellular immune responses
      in BALB/c mice. Furthermore, immunization with pVAX1-p24 DNA prime and protein
      boost induced 7.3 to 8.0-fold greater p24-specific humoral responses than pVAX1
      p24 DNA prime and boost, while the cellular immune responses induced by combined
      immunization was lower. The results suggested that pVAX1-p24 DNA and P24 protein
      vaccine is a promising HIV-1 vaccine, and the selections of the immunization
      strategies are important for the immunization results.

PMID- 21845845
TI  - [Development of a killed but metabolically active anthracis vaccine candidate
      strain].
AB  - Anthrax is a zoonosis caused by Bacillus anthracis, which seriously affects human
      health. In recent years, a special phenomenon is found that the metabolic active
      of a bacterium remains after it is killed. To development of a KBMA (killed but
      metabolically active) Bacillus anthracis vaccine candidate strain, a plasmid pMAD
      and a recombinase system Cre-loxP were used to knockout the uvrAB gene of B.
      anthracis AP422 which lacks both of two plasmids pXO1 and pXO2. The results of
      PCR and RT-PCR shows that uvrAB genes were deleted from B. anthracis AP422
      chromosome successfully. The constructed B. anthracis AP422deltauvrAB was
      inactivated by photochemical treatment (PCT) including an exposure in a long-wave
      length ultraviolet (UVA) light and a treatment of 8-Methoxypsoralen (8-MOP), then
      the metabolic activity were detected by the method of MTS. The results showed
      that the killed B. anthracis AP422deltauvrAB maintained a highly metabolic
      activity for at least 4 hours, showing a state of KBMA. The KBMA strain of B.
      anthracis AP422deltauvrAB provides the prospective vaccine candidate strain for
      anthrax.

PMID- 21845846
TI  - [Enhancement of cellular and humoral immune responses of HBV DNA vaccine by HSP70
      and gp96].
AB  - While currently therapeutic vaccines for chronic hepatitis B virus (HBV)
      infection are actively being developed to complement standard antiviral
      treatments, their immune activity, especially T cell activity, remains to be
      further improved. Here, we investigated the role of heat shock proteins HSP70 and
      gp96 on cellular and humoral immunity, using the main structure antigens of
      hepatitis core (HBcAg) and surface (HBsAg) as the DNA vaccine. By ELISPOT (enzyme
      linked immunospot assay), IFN-gamma intracellular staining, [3H]-thymidine
      incorporation and ELISA (enzyme linked immunosorbent assay) analyses, we showed
      that immunization with HBsAg/HBcAg DNA formulation along with HSP70 or gp96
      induced significant increase of T-cell (about 1-6-fold) and antibody (about 20%
      60%) immunity against HBsAg and HBcAg. These results may provide bases for
      designing HSP70- and gp96-based vaccines aimed at eliciting T-cell responses for
      therapeutic applications.

PMID- 21845847
TI  - [Preparation and application of a colloidal gold strip to detect the rabies
      antibody].
AB  - To develop a specific, rapid, and convenient immunochromatography assay (ICA) to
      detect the rabies antibody in clinical sample from immuned dogs by rabies
      vaccine. Colloidal gold particles labeled with purified rabies virus (CVS11) were
      used as the detector reagent. The staphylococcal protein A (SPA) and pured rabbit
      anti-rabies virus IgG were blotted on the test and control regions of
      nitrocellulose membrane. Then the strip was assembled with sample pad, absorbing
      pad, and dorsal shield. The assay samples (261 dog's serum) were collected from
      Wildlife Rabies Disease Diagnostic Laboratories of Ministry of Agriculture in
      China, Institute of Military Veterinary, Academy of Military Medical Sciences and
      other six provinces, including rabies virus positive and negative serum. The
      performance of the strip was compared to fluorescent antibody virus
      neutralization test. The neutralizing antibody titer could be detected above 0.5
      IU. The strip did not change of performance when stored at room temperature for
      12 months. It may offer reference of neutralizing antibody titer level after dogs
      immuned rabies vaccine and determin whether the dogs need to be immuned again.

PMID- 21845848
TI  - [Indirect ELISA for detection of antibodies against swine influenza virus
      (H1N1)].
AB  - In order to detect antibody against swine influenza virus (H1N1), HA1 region of
      hemagglutinin gene in epidemic swine influenza virus (H1N1) strain was amplified
      and subcloned into prokaryotic expression vector pET30a. Then recombinant HA1
      protein was expressed by Escherichia coli BL21. The purified recombinant HA1
      protein was obtained after the treatment of denaturing, refolding and affinity
      chromatography with immobilized nickel chelating NTA (Ni-NTA). An indirect enzyme
      linked immunosorbent assay (ELISA) method was established using the purified
      protein as antigen. Then 785 swine serum samples collected during 2008-2009 were
      detected by this method, and the positive ratio was 15.54%. There were
      diversities among provinces (8%-47%). The diagnostic specificity and diagnostic
      sensitivity of this method arrived at 91% and 95% respectively, using the results
      of IDEXX ELISA kit as reference.

PMID- 21845849
TI  - [Preparation and characterization of follwing the national standard anti-Brucella
      abortus serum, bovine].
AB  - To prepare anti-Brucella abortus serum used for calibrate the agglutination test
      follwing the national standard, 4 anti-Brucella abortus sera were obtained from 4
      cows infected with Brucella abortus naturally. By potency testing, the third
      serum was selected. Sterility, vaccum degree, residual moisture, uniformity and
      stability of this standard material were tested and proved to meet the national
      standard. Referring to the international standard, RBT (Rose-Bengal plate
      agglutination test), SAT (standard tube agglutination) and CFT (complement
      fixation test) titers of this standard material were measured to be 1:160 "+" 1:2
      400 "++" and 1:800 "++", which are identical with the collaborative assay
      results. International unit of the standard material is 4 000 IU/mL.

PMID- 21845850
TI  - [Selection and genotyping of lactobacillus with potential preventive effect by
      repetitive element sequence-based PCR analysis].
AB  - We selected and characterized isolates of Lactobacillus crispatus (L. crispatus)
      for potential preventing infections of the female reproductive tract. We cultured
      vaginal swabs from healthy volunteers on de Man, Rogosa and Sharpe (MRS) agar and
      identified the isolates at the species level by 16S rRNA sequence and genotyped
      the isolates of Lactobacillus by PCR amplification of repetitive bacterial DNA
      elements (rep-PCR). Furthermore, 10 L. crispatus strains were assessed for
      hydrogen peroxide (H2O2) and acid production. Overall 65 isolates were confirmed
      to be Lactobacillus by sequence analogy, among them 19 were L. crispatus, 17 were
      Lactobacillus jensenii and 12 were Lactobacillus fermentum. rep-PCR produced
      specie and strain-specific genomic fingerprints for the Lactobacillus isolates.
      The selected 10 L. crispatus isolates produced highly acidic environment after
      growth in MRS. The isolates T22-3 and T29-5 demonstrated high production of H2O2.
      This study indicated that there are individual differences with vaginal
      Lactobacillus colonization, and strain diversity within vaginal L. crispatus
      isolates, T22-3 and T29-5 might be candidates for restoring urogenital health
      environment in females.

PMID- 21845851
TI  - [Association of ankle-brachial index with clinical coronary heart disease, stroke
      in aged Chinese hypertensive men].
AB  - OBJECTIVE: To assess the clinical significance of ankle-brachial index(ABI) in
      aged Chinese hypertensive men and to determine the association of ABI with
      clinical coronary heart disease, stroke. METHODS: Ankle-brachial index (ABI) was
      measured by means of peripheral vascular lab in aged hypertensive men from 301
      Hospital and Anzhen Hospital while the clinical characteristics of the study
      population were investigated and collected. ABI < or = 0.9 was defined as
      peripheral arterial disease (PAD), 1.01 - 1.30 as borderline PAD. RESULTS: There
      were 244 aged Chinese hypertensive men with antihypertensive treatment and with
      mean age 76.47 +/- 9.75 enrolled in this study, in whom 15 men with missing data
      except general information and ABI measurement. The mean ABI was 0.941 +/- 0.258
      with the highest frequency 1.01 - 1.30. Eighty five men were diagnosed as PAD, 22
      as borderline PAD, 135 normal ABI and 2 with ABI > 1.3. ABI and rate of
      hypertension control in PAD and borderline PAD men were significantly lower than
      those with normal ABI. In both PAD and borderline PAD patients, the hypertension
      duration (except in borderline PAD), creatinine level, neutrophil count (except
      in borderline PAD), percentage of alcohol drinking, prevalence of diabetes
      mellitus (except in borderline PAD), coronary artery disease, stroke and
      dyslipidemia (except in borderline PAD) were significantly higher than those with
      normal ABI patients. The prevalences of PAD, borderline PAD, coronary artery
      disease and stroke in this study population were 35.1%, 9.1%, 64.0%, 40.5%,
      respectively. The prevalences of PAD, borderline PAD, coronary artery disease and
      stroke increased significantly with increasing age. Logistic regression analysis
      showed that lower ABI was inversely associated with clinical coronary artery
      disease and stroke after adjustment for age, body mass index, hypertension
      duration, rate of hypertension control, systolic blood pressure, diastolic blood
      pressure, status of smoking, alcohol drinking, diabetes mellitus, dyslipidemia.
      The fully-adjusted odds ratios (ORs) for PAD and borderline PAD group compared
      with normal ABI group for the prevalence of coronary artery disease, and stroke
      demonstrated that these conditions were conversely related to ABI. CONCLUSION:
      Aged hypertensive men have high prevalence of PAD. Low ABI level was
      independently associated with coronary artery disease and stroke.

PMID- 21845852
TI  - [Study on SNP/T3541G in erythropoietin gene in ethnic population from northern
      China].

PMID- 21845853
TI  - [Clinical usefulness of carotid arterial wave intensity in noninvasively
      assessing left ventricular performance in different hypertensive remodeling
      hearts].
AB  - OBJECTIVE: To evaluate wave intensity (WI) on left ventricular (LV) performance
      in the different hypertensive remolding hearts. METHODS: 105 hypertensive and 98
      control subjects were underwent noninvasive evaluation of carotid arterial wave
      intensity, LV structure and function. RESULTS: (1) There were increasing trends
      in the levels of blood pressure, LV end-diastolic diameter and LV mass index in
      the control, normal geometry group, concentric remodeling group, concentric and
      eccentric hypertrophy group. LV ejection fraction increased in the concentric
      hypertrophy group and decreased in the eccentric hypertrophy group in which mid
      wall fractional shortening showed a decreasing trend. LV diastolic filling
      pressure presented increased progression accompanied by LV remodeling (P < 0.05).
      (2) Transient acceleration wave intensity (W1) in hypertensive subjects were
      higher than that in the control (P < 0.05). Transient deceleration wave intensity
      (W2) was lower than that in the control (P < 0.05). (3) W1 in the concentric
      hypertrophy group was higher and lower in the eccentric hypertrophy, compared
      with that in the control group, normal geometry group and concentric remodeling
      group (P < 0.05). W2 was lower in concentric hypertrophy group and eccentric
      hypertrophy group than that in the control, normal geometry group and concentric
      remodeling group (P < 0.05). CONCLUSION: WI is a noninvasively obtained,
      clinically useful parameter for evaluation of LV performance.

PMID- 21845854
TI  - [The distribution and mechanism of coronary arteriole cell resting membrane
      potential in guinea pigs].
AB  - OBJECTIVE: To investigate the distribution and mechanism of coronary arteriole
      (CA) cell resting membrane potential (RP) in guinea pigs. METHODS: Cell RP was
      recorded by intracellular microelectrode in isolated guinea pig coronary
      arteriole (diameter < 100 microm). RESULTS: (1) Experiments were carried out in
      112 cells with a mean RP of (-65 +/- 4.2)mV, the distribution of coronary
      arteriole cell RP fitted by Gaussian function was bimodal, one peak was -43 mV
      termed high RP, the other was -74 mV termed low RP. 10 mmol/L K+ and 3 micromol/
      L acetylcholine(ACh) induced hyperpolarization in high-RP cells with (-7.4 +/-
      0.87) mV (n = 13) and (-15 +/- 1.24) mV (n = 16) respectively, and induced
      depolarization in low-RP cells with (9.6 +/- 1.2) mV (n = 23) and (8.7 +/- 0.69)
      mV (n = 15) respectively. (2) The inward rectifier K+ channel (K(ir)) blocker
      Ba2+ caused concentration-dependent depolarization in low-RP cells with an EC50
      of 120 micromol/L 100 micromol/L Ba2+ or higher could shift low-RP cells to high
      RP state, the response of these cells to high K+ and ACh became a
      hyperpolarization. CONCLUSION: The distribution of coronary vascular cell RP is
      bimodal, high K+ and ACh induce different responses in low and high RP cells. The
      two RP states are exchangeable mainly due to all-or-none conductance changes of
      K(ir).

PMID- 21845855
TI  - [Mitochondrial permeability transition pore opening changes with age and its
      mechanism].

PMID- 21845856
TI  - [Effect of hypoxia on activation of the peripheral blood T lymphocyte in rats].
AB  - OBJECTIVE: To explore the effect of hypoxia on the peripheral blood T lymphocyte
      subsets and co-stimulatory molecules in rats so as to provide the basis for
      studying the intervention measure. METHODS: Before hypoxia and during hypoxia at
      8 000 m for 8 h, 3 d, 6 d and 10 d the change of peripheral blood T lymphocyte
      subsets and co-stimulatory molecules in rats were detected by flowcytometer with
      three-color immunofluorescence label. RESULTS: Rats were exposed to hypoxia at 8
      000 m for 8 hours, and CD3+, CD8+, CD8+ CD28- lymphocyte percentages were
      significantly decreased (P < 0.01) compared with that before hypoxia. After 3
      days of hypoxia, besides aforesaid change, CD4+ CD28+ lymphocyte percentage also
      prominently decreased (P < 0.01) and CD4+ CD28- prominently increased (P < 0.01).
      After 6 and 10 days of hypoxia, CD3+, CD4+ lymphocyte percentages were further
      decreased, while CD8+ CD28+ lymphocyte percentage significantly increased (P <
      0.01). CONCLUSION: After exposed to hypoxia at 8 000 m for 8 hours and 3 days,
      activation of CD8+ and CD4+ T lymphocyte was prominently decreased, while with
      the prolong of exposed time activation of CD8+ T lymphocyte was significantly
      increased.

PMID- 21845857
TI  - [Effects of carbon monoxide inhalation on severe limb ischemia/reperfusion injury
      and its damages lead to shock].
AB  - OBJECTIVE: To study the protective effect of carbon monoxide (CO) inhalation on
      the serious limb ischemia/reperfusion (I/R) injury, and which effects caused to
      shock in rats. METHODS: 36 SD rats were randomly divided into I/R, I/R + CO (RC),
      sham operation (S) groups. I/R injury models were made by the occlusion of the
      femoral artery for 8 h and the reperfusion for 12 h, 10 d. Before reperfusion of
      2 h, RC group started to breathe medical air containing CO (the volume fraction
      of CO: 0.075%) continuously, until after reperfusion for 4 h, a total of
      inhalation 6 h. S, I/R groups exposed to air, breathe freely. Caudal artery
      pressures (CAP), ten days survival rate, serum lactate dehydrogenase (LDH) and
      creatine kinase (CK) activity, limb wet - to - dry weight ratio (W/D) and the
      pathologic changes of limb were observed. RESULTS: Once the reperfusion started,
      the CAP decreased rapidly in I/R group, and the mean reduced to(5.3259 +/-
      0.3832) kPa when reperfusion for 8 h. Compared to I/R group, the CAP decreased
      slower and smaller in RC group, moreover, its mean reduced to (8.3300 +/- 0.4224)
      kPa when reperfusion for 8 h. The 10 d survival rate in I/R group was that 8 rats
      died all between reperfusion for 13 - 20 h. Only 1 rat died in RC group and the
      other 7 rats were still alive when reperfusion for 10 d. Compared to I/R group,
      the pathological features of the ischemic limb were significant ly improved, and
      the figures of W/D, serum LDH and CK value were remarkable lower in RC group (P <
      0.05). CONCLUSION: Inhaling exogenous low-dose CO has a reverse regulation in the
      blood pressure decline caused by serious limb I/R injury in rats. And at the same
      time, it can effectively prevent the occurrence of shock, reduce physical damage,
      significantly increase the survival rate of animals.

PMID- 21845858
TI  - [The expression of ACE, AT1, ACE2, MAS on heart from WKY and SHR].

PMID- 21845859
TI  - [The protective of Shenfu injections on hemodynamics and myocardial enzyme after
      myocardial ischemia/reperfusion injury].
AB  - OBJECTIVE: To study the protective effect of Shenfu (Chinese traditional
      medicine) injections on myocardial ischemia/reperfusion (I/R) injury in rabbits.
      METHODS: Thirty rabbits were divided into three groups (n = 10) randomly: control
      group, myocardial ischemia/ reperfusion group (MI/RI) and Shenfu injections
      extract group, three groups of rabbits were fed respectively with standard diet.
      After giving medicine 10 minutes, the myocardial ischemia/reperfusion injury
      animal model was established by ligaturing rabbits left ventricutar branch of
      coronary artery, and observing the changes of enzyme/hemodynamics during
      myocardial ischemia/reperfusion. RESULTS: In model group myocardial function of
      shrink went down, the amount of malondialdehyde (MDA) was higher, the activity of
      superoxide dismutase (SOD), glutathine peroxidease (GSH-Px), Na(+) -K(+) -ATP and
      Ca(2+) -ATP were lower, lactic dehydrogenase (LDH) and creatine kinase(CK) were
      released compared with those in model group. Shenfu injections could recover left
      ventricular systolic pressure (LVSP) and +/- dp/dt(max), decrease left
      ventricular end-diastolic pressure(LVEDP), inhibit the increasing of MDA, LDH and
      CK, and increase the activaty of SOD, GSH-PX, Na(+) -K(+) -ATP and Ca(2+) -ATP.
      CONCLUSION: Shenfu injections can obviously protect myocardial
      ischemia/reperfusion injury.

PMID- 21845860
TI  - [Effects of hydrogen sulfide on myocardial mitochondrial injury during acute
      myocardial ischemia in rats].
AB  - OBJECTIVE: To investigate the effect of hydrogen sulfide (H2S) on mitochondrial
      function in acute myocardial ischemia in rats. METHODS: Acute myocardial ischemia
      models were established by ligating the left anterior descending coronary artery
      (LADC) of rats. Fourty-eight male SD rats were randomly divided into 6 groups (n
      = 8): sham operation group, ischemia group, ischemia + sodium hydrosulfide (NaHS)
      low, middle and high dose groups and ischemia + DL-proparglycine(PPG) group. The
      ultrastructures of myocardial mitochondria were observed with electron
      microscope. The content of H2S in plasma and the activity of cystathionine-gamma
      lyase (CSE) in myocardial tissue of rats were respectively detected. The swelling
      and activity of myocardial mitochondria were determined. The activities of
      ATPase, GSH-Px, SOD and the content of malondial-dehyde (MDA) in myocardial
      mitochondria of rats were also measured. RESULTS: Compared with those of the sham
      operation group, the content of H2S in plasma, the activity of CSE in myocardial
      tissue and the activity of myocardium mitochondria were significantly decreased.
      The activities of ATPase, SOD, GSH-Px in myocardial mitochondria were
      significantly decreased, The content of malondial dehyde(MDA) in myocardial
      mitochondria and the swelling of mitochondria were distinctly increased in the
      ischemia group (P < 0.01). Compared with those of the ischemia group, the content
      of H2S in plasma and the activity of CSE in myocardial tissue were increased, and
      the activities of mitochondria, ATPase, SOD, and GSH-Px in myocardial
      mitochondria were significantly increased in ischemia + NaHS low, middle and high
      dose groups; the swelling of mitochondria and the content of MDA in myocardial
      mitochondria were significantly decreased in ischemia + NaHS middle and high-dose
      groups (P < 0.05 or P < 0.01). The administration of PPG could partially reduce
      the myocardial protection of hydrogen sulfide (P < 0.05 or P < 0.01). CONCLUSION:
      It could be concluded that the administration of hydrogen sulfide could enhance
      the activities of mitochondrial ATPase, SOD, GSH-Px, decrease the level of
      mitochondrial lipid peroxidation, and play a protective effect against acute
      myocardial ischemia.

PMID- 21845861
TI  - [The effects of thrombopoietin on the fibrogenesis of bone marrow stromal cells
      in absence of megakaryocytes].
AB  - OBJECTIVE: In order to investigate whether or not thrombopoietin (TPO) could
      promote the fibrogenesis of bone marrow stromal cells in absence of
      megakaryocytes (MKs). METHODS: Improved dexter culture system with various TPO
      concentrations was used for ex vivo culture of bone marrow stromal cells.
      Relative proliferation index, the expressions of fibronectin, laminin and type IV
      collagen, and the systhesis of type III procollagen were detected at different
      time points during culture process. RESULTS: TPO stimulated the proliferation of
      bone marrow stromal cells. Relative proliferation index of the stromal cells
      increased with the TPO concentration increasing, and was not related to the
      exposure time. The expressions of fibronectin, laminin, and type IV collagen
      appeared stronger in the TPO groups than those in the control group. But the
      expressions of these molecules were not dependent upon the culture time. TPO
      could accelerate the synthesis of type III procollagen in bone marrow stromal
      cells, and this acceleration was unrelated to the TPO concentration. CONCLUSION:
      These findings suggested that TPO could stimulate the stromal cells with a
      consequence of increased syntheses and secretions of the extracellular matrix and
      collagen in absence of MKs. In other words, TPO could promote the fibrogenesis of
      bone marrow stromal cells without the existence of MKs.

PMID- 21845862
TI  - [Correlation between atrial fibrillation and serum brain natriuretic peptide].

PMID- 21845863
TI  - [Experimental study of recording and analysing electrophysiological signals from
      corticospinal tract in rats].
AB  - OBJECTIVE: To explore the recording method of the electrophysiological signals in
      corticospinal tract (CST) of adult rats by plugging microelectrodes and analyze
      the characteristics of these signals. These could provide some valuable and basic
      neural electrophysiological information for further research of recovering and
      refunctioning after spinal cord injury. METHODS: The microelectrodes were plugged
      into the corticospinal tract at the T8 spinal section of Sprague-Dawley rats and
      the neuro-electrical signals were identified and recorded from CST by means of
      the Cerebus System. The characteristics of the recorded signals were described
      with the help of the Offline sorter and Neuroexplorer softwares, including the
      wavelength, amplitude, discharging frequency, the synchrony among the multi
      discharging units from the same electrode and two different electrodes, analysis
      of interspike interval (ISI), etc. RESULTS: The continuous and steady spontaneous
      electrophysiological signals were recorded from CST. Three or four types of
      discharging signals originated from different discharging units were collected
      with each electrode. The waveform of the signals appeared bidirectional. The
      wavelengths were 0.6 - 1.3 ms with wave amplitudes at a grade of hundred
      microvoltage and high signal-noise ratios. The LFB staining proved that the
      electrodes were accurately plugged into the corticospinal tract. CONCLUSION: The
      neuro-electrical signals at a grade of hundred microvoltage could be recorded
      stably from the corticospinal tract of rats by the Cerebus System with the
      microelectrodes, which provided valuable and basic neural electrophysiological
      information for further research on recovering and refunctioning after spinal
      cord injury (SCI) by analyzing the characteristics of electrophysiological
      signals.

PMID- 21845864
TI  - [Calcitonin gene related peptide is involved with exercise-induced
      cardioprotection].

PMID- 21845865
TI  - [Effects of neuroactive steroid allopregnanolone on the damage of cortical
      neurons].
AB  - OBJECTIVE: To investigate the protective mechanism of neuroactive steroid
      allopregnanolone on N-methyl-D-aspartate (NMDA) induced toxicity in primary mouse
      cortical neurons. METHODS: Primary cultured mouse cortical neurons were subjected
      to allopregnanolone, the expression of beta-aminobutyric acid receptor beta2
      subunit (beta2-GABA-R) mRNAs was detected by RT-PCR and Akt phosphorylation was
      assayed by Western blot using Akt-phosphoserine 473-specific antibody. After the
      cultured mouse cortical neurons were pretreated with or without allopregnanolone
      prior to treatment with NMDA , DNA isolated was analyzed by agarose gel
      electrophoresis and proteins collected were analyzed by Western blot with anti
      cleaved-PARP, anti-cleaved caspase-3, and anti-cleaved caspase-9 antibodies.
      RESULTS: When cultured mouse cortical neurons were exposed to allopregnanolone
      both the expression of beta2-GABA-R mRNAs and Akt phosphorylation increased.
      Allopregnanolone inhibited the NMDA-induced apoptosis and decreased the level of
      active-PARP, active-caspase-3 and active-caspase-9 notably at a final
      concentration of 5 x 10(6) mol/L. CONCLUSION: Pretreatment with allopregnanolone
      may be neuroprotective on NMDA-induced neuronal cells apoptosis by increasing
      beta2-GABA-R expression and Akt phosphorylation.

PMID- 21845866
TI  - [Effect of ischemic postconditioning on the expression of P38 after focal
      cerebral ischemia reperfusion in rat].

PMID- 21845867
TI  - [The study of plasma proteomic changes in a patient with high-altitude cerebral
      edema].
AB  - OBJECTIVE: High-altitude cerebral edema (HACE) is one of the most serious acute
      mountain sickness and its underlying mechanism is still unknown clearly. The aim
      of this study was to determine the changes of plasma proteins in high altitude
      cerebral edema patients for discovering essential biomarkers used for the routine
      prophylaxis, diagnosis and treatment. METHODS: Plasma protein profiling two
      dimensional gel electrophoresis followed by mass spectrometry was used to explore
      protein alterations in one patient with high-altitude cerebral edema (HACE).
      Striking differences in two-dimensional gel proteomes of plasma were observed
      between high-altitude cerebral edema (HACE) and high-altitude pulmonary edema
      (HAPE) and between high-altitude cerebral edema (HACE) and mild acute mountain
      sickness (mAMS). Furthermore, apolipoprotein E altered in high-altitude cerebral
      edema was validated by ELISA. RESULTS: Different six spots were found in this
      study from the comparison between HACE and HAPE, and there were different six
      spots which were detected from the plasma of HACE patient in comparison to mAMS.
      Apolipoprotein E was identified in the two groups of comparative maps and results
      of ELISA consisted with the results of 2-DE. CONCLUSION: In this study, we used
      proteomic approach to explore HACE firstly and found different proteins that were
      probably associated with HACE. This would offer a clue to a better understanding
      of HACE for precaution, diagnosis and treatment.

PMID- 21845868
TI  - [The primary study on changes of proteome of the prefrontal cortex between
      morphine-addicted and withdrawal rats].

PMID- 21845869
TI  - [Expression and function of autophagy after ischemia/reperfusion in rats
      hippocampus neuron].
AB  - OBJECTIVE: To explore the expression of autophagy after ischemia/reperfusion and
      its possible function in rats hippocampus neurons. METHODS: After 2 hours oxygen
      glucose deprivation and different periods time of reperfusion (OGD/R) treatment
      in primary hippocampal neurons, neuron viability was evaluated by MTT assay,
      specific structure of autophagosome and specific protein of autophagy microtubule
      associated protein 1 light chain 3 B (LC3B) were detected by transmission
      electron microscope and immunofluorescence respectively. The inhibitor of
      autophagy 3-Methyladenine (3-MA) was also used to exam the viability of neurons.
      RESULTS: Treatment by OGD/R markedly reduced neuronal viability. Compared to the
      control group, autophagy existed in different time periods after OGD/R shown both
      in transmission electron microscope and immunofluorescence. Application of 3-MA
      significantly reduced neuronal viability. CONCLUSION: Oxygen-glucose deprivation
      can activate autophagy in rat hippocampus neurons, which may resist the injury
      during ischemia/reperfusion.

PMID- 21845870
TI  - [The progressive effects of chronic intermittent hypoxia on cognitive function
      and the cholinergic neuron in rats].
AB  - OBJECTIVE: To investigate the relation between the progressive effects of chronic
      intermittent hypoxia (CIH) on cognitive function and the change of cholinergic
      neuron. METHODS: Forty adult male Sprague-Dawley rats were randomly averagely
      divided into four groups: control group, CIH 1 week group, CIH 3 week group and
      CIH 5 week group. The cognitive function was assessed by the Morris Water Maze.
      The necrosis neurons in prefrontal cortex and hippocampus were observed and
      counted. The cholin acetyltransferase (ChAT) immunostained cells in prefrontal
      cortex and hippocampus were identified and quantitated. RESULTS: The spatial
      learning and memory impairments progressed from 1 to 5 5 weeks in rats. Compared
      with the control group, the cognitive impairments in CIH5w group were significant
      (P < 0.05). The degeneration or necrosis neurons in prefrontal cortex and
      hippocampus were significantly increased in CIH rats, and worsen gradually along
      with the hypoxia. The ChAT immunostained cells in prefrontal cortex and
      hippocampus were gradually reduced. The ChAT immunostained cells of prefrontal
      cortex and hippocampus in CIH3w group and CIH5w group were less than that in
      control group (P < 0.05). CONCLUSION: Chronic intermittent hypoxia induced slowly
      progressive spatial learning and memory impairments in rats, which maybe
      associated with the damage of neurons and the reduction of ChAT in prefrontal
      cortex and hippocampus.

PMID- 21845871
TI  - [The anti-injury effect of breviscapine injection on the hypoxic ischemic brain
      damage of neonatal rats and the expression of Bcl-2 and Bax].
AB  - OBJECTIVE: To observe the protective effect of Breviscapine injection on the
      hypoxic ischemic brain damage of neonatal rats, and the expression of Bcl-2 and
      Bax. METHODS: In this experiment 7-day-old newborn rat with hypoxic-ischemic
      brain damage model was used and divided into four groups: sham group, model
      group, control with sterile water for injection group and Breviscapine injection
      group. Breviscapine injection group was divided into large, medium, and small
      doses. Used thionin staining and immunohistochemical staining to assay the
      neuronal density, histological grade, and the expresssion of Bcl-2 and Bax
      protein in the CA1 hippocampus of each group , the number of positive cells and
      the integral optical density (IOD) of the immunostaining on Bcl-2, Bax protein
      expression in the CA1 hippocampus. RESULTS: Sham group, there was no significant
      neuronal damage and no obvious positive cells of Bcl-2 and Bax in the CA1
      hippocampus. In model group and control with sterile water for injection group,
      the level of Bcl-2, Bax expression peaked at 3 d after hypoxic-ischemic brain
      damage (HIBD) (P < 0.05 vs other groups), the value of neuronal density (ND) was
      decreased, and histological grade (HG) was increased compared with that in the
      sham group (P < 0.05). Breviscapine injection group, compared with control with
      sterile water for injection group, the expression of Bcl-2 protein was further
      increased, IOD value increased, while the expression of Bax protein was
      decreased, IOD value decreased, the value of ND increased, and HG decreased.
      CONCLUSION: Breviscapin injection maybe reduce the delayed neuronal death, and
      reduce the apoptosis of neuron after severe brain injury through improving the
      expression of Bcl-2 protein and inhibiting expression of Bax. The study would
      provide a fine theoretical foundation for clinical therapy of neonatal HIBD.

PMID- 21845872
TI  - [Changes of VEGF, TNF-alpha, IL-6 and NO in serum of patients with HAPE].
AB  - OBJECTIVE: To explore the possible pathophysiological process and mechanisms
      underlying the development and formation of high altitude pulmonary edema(HAPE)
      by observing the changes in contents of VEGF, TNF-alpha, IL-6 and NO in serum
      from the initiated and recovery of HAPE patients. METHODS: We studied 10 HAPE
      patients in a Chinese population. The patients were divided into two groups
      including HAPE initiate group and the recovery group. Contents of VEGF, TNF
      alpha, IL-6 and NO in serum of the two groups were determined to study the
      process of HAPE. RESULTS: VEGF levels in the HAPE initiate one and the recovery
      groups were (167.9 +/- 26.5 and 53.1 +/- 17.0 pg/ ml), respectively. There was a
      significant decrease of VEGF content in recovery one compared to the HAPE group.
      The same results for TNF-alpha were gained. The levels of TNF-alpha in recovery
      group was much lower than that in the HAPE initiate one. They were (29.2 +/- 6.8)
      pg/ml and (86.2 +/- 24.1) pg/ml, respectively. The contents of IL-6 in HAPE
      initiate group and the recovery group were (32.3 +/- 16.5) pg/ml and (12. 5 +/-
      8.0) pg/ml, respectively. But no significance existed. The level of NO in HAPE
      initiate group was (33.8 +/- 3.3) micromol/L, and it remarkably increased to
      (74.1 +/- 6.2) micromol/L in recovery one. CONCLUSION: VEGF, TNF-alpha, IL-6 and
      NO participated in the different aspects of the pathophysiological process and
      might have influence on HAPE.

PMID- 21845873
TI  - [Effect of lactulose on interleukin-18 madiatid multiple orgern function in
      severe burned rats].

PMID- 21845874
TI  - [Primary study on changes of serum proteomics in rabbit superior mesenteric
      artery occlusion shock].
AB  - OBJECTIVE: To explor the changes of serum proteomics in rabbits superior
      mesenteric artery occlusion (SMAO) shock as well as its possible effect in SMAO
      shock. METHODS: SMAO shock model in rabbits were induced by occlusion of the
      superior mesenteric artery, serum samples were obtained from rabbits before and
      after SMAO shock, proteins in samples were separated by two-dimensional
      electrophoresis(2-DE), spots in the 2-DE map were detected and evaluated by
      PDQuest software 8.0. The spots with different expression level were subjected to
      matrix assisted laser desorption/ionization-time of flight-time of flight-mass
      spectrometry (MALDI-TOF-TOF-MS) for identification, the protein database was
      searched to further characterized the differential proteins. RESULTS: 19
      differential protein spots were screened out in the 2-DE maps, 11 proteins were
      up-regulated and 8 proteins were down-regulated in SMAO shock rabbits' s serum. 4
      of the 19 differential protein spots were selected for MALDI-TOF-TOF-MS study,
      and 2 of the 4 differential protein spots were identified satisfactoryly as
      paraoxonase and haptoglobin, which content were increased in rabbits' s serum
      after SMAO shock. CONCLUSION: Serum proteomics of rabbit change remarkablely
      before and after SMAO shock, paraoxonase and haptoglobin may be associated with
      the compensation after SMAO shock.

PMID- 21845875
TI  - [Cyclooxygenase-2 overexpression and vascular endothelial growth factor
      expression in pharyngeal tissue of patients with OSAHS correlates with
      angiogenesis].
AB  - OBJECTIVE: To reseach the correlations between cyclooxygenase-2 (COX-2) and
      vascular endothelial growth factor (VEGF) expressions and angiogenesis in
      pharyngeal tissue of patients with obstructive sleep apnea hypopnea syndrome
      (OSAHS). METHODS: Biopsies were obtained by uvulopalatopharyngoplasty from 40
      patients with mild to severe OSAHS. Control specimens of palatopharyngeal and
      palatoglossal arch mucosa were retreved from 6 patients with chronic tonsillitis
      and proved have no related disorders. HE was used to observe the changes of
      pharyngeal tissue, immunohistochemical staining with antibodies against COX-2,
      VEGF, microvessel density (MVD) (marked with CD34). RESULTS: COX-2 and VEGF
      mainly expressed at pavement-epithelium and glandular epithelium of pharyngeal
      tissue, and stronger COX-2 and VEGF expression was found in midrange and severe
      OSAHS than mild and control group (P < 0.01), so as MVD. COX-2 expression was
      correlated positively with VEGF expression, and had significant correlation with
      MVD. VEGF expression had the same correlation with MVD. These three targets had
      considerable relation with apnea hypopnea index (AHI) and lowest O2 saturation at
      night. CONCLUSION: There was angiogenesis which had important relationship with
      hypoxia degree in patients of OSAHS, and COX-2 and VEGF play a crucial role in
      its development.

PMID- 21845876
TI  - [Effect of polydatin on learning and memory and expression of NR2B in the
      prefrontal cortex of rats with chronic alcoholism].

PMID- 21845877
TI  - [Improvement effect of vitamins B1, B2 and PP supplementation on substance
      metabolism of mice exposed to acute hypoxia].
AB  - OBJECTIVE: To explore the improvement effect of vitamins B1, B2, PP
      supplementation to the metabolism changes of carbohydrates, lipids, protein and
      energy in mice exposed to acute hypoxia. METHODS: Fifty male Kunming mice were
      randomly divided into normal, acute hypoxia, acute hypoxia plus 2 times, 4 times
      and 8 times vitamins B1, B2, PP supplemented groups. All mice were fed
      corresponding diets for two weeks and then except the normal group were exposed
      to a simulated altitude of 6 000 meters for 8 hours. The changes of glucose,
      pyruvate, lactate, urea nitrogen, free fatty acids and beta-hydroxybutyric acid
      from serum, liver glycogen and blood adenosine triphosphate (ATP) concentration
      were measured. RESULTS: After being exposed to acute hypoxia, the mice glucose,
      liver glycogen, pyruvate, lactate, free fatty acids, beta-hydroxybutyric acid and
      urea nitrogen level were increased significantly (P < 0.05), while blood ATP
      concentration was decreased. In the vitamins B1, B2 and PP supplemented groups,
      these changes were improved. CONCLUSION: The significant changes in carbohydrate,
      lipid and protein metabolism were observed in mice exposed to acute hypoxia, and
      the supplementation of vitamins B1, B2 and PP was proved to be beneficial in
      improving some metabolic pathways. It is suggested that the supplemented dose of
      four times was good.

PMID- 21845878
TI  - [The reduced antioxidation ability in the serum in the early Parkinson's disease
      rats].

PMID- 21845879
TI  - [Effects of training on plasma content of nitric oxide, endothelin and NO/ET
      system in rats fed with high methionine diet].
AB  - OBJECTIVE: To observe the effects of training on plasma content of NO, ET and
      NO/ET system in rats fed with high methionine diets. METHODS: Male Wistar rats
      were randomly divided into normal diet group (CR), high methionine diet group
      (MR) and high methionine diet plus 90 min swimming group (T+ MR). Rats in MR and
      T+ MR group were fed with the diet which contained 3%of methionine for eight
      weeks, but rats in control group were fed with ordinary diet. After breeding for
      eight weeks homocysteine (Hcy) level, T-NOS, NO and ET were measured. RESULTS:
      Plasma homocysteine of MR increased twofold as compared with that of CR,whereas
      plasma NO/ET of MR descended significantly (P < 0.05), suggesting that
      hyperhomocysteinemia was induced by the high methionine diet, and plasma NO/ET
      system was out of balance. Plasma homocysteine content of T+ MR obviously
      descended, plasma T-NOS, NO and NO/ET ascended obviously (P < 0.05) as compared
      with that of MR, and the above indicators of group T + MR were not different as
      compared with that of CR (P > 0.05). CONCLUSION: Proper training can descend
      plasma homocysteine level of rats fed with high methionine diet and better
      balance between NO and ET to prevent developing of hyperhomocysteinemia.

PMID- 21845880
TI  - [The roles of PPAR-gamma/PGC-1alpha to Nrf2/gamma-GCS-h in lung of guinea pigs
      with bronchial asthma].
AB  - OBJECTIVE: To investigate the expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma
      GCS-h in lung of guinea pigs with bronchial asthma, and to explore the roles of
      them. METHODS: Forty adult male guinea pigs were randomly divided into 4 groups:
      the control group (group A), asthmatic group ( group B), dexamethasone group
      (group C) and rogridone group (group D), 10 guinea pigs in each group. The
      asthmatic model was established by the ovalbumin challenge method. Expressions of
      PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h mRNA in lung tissue were assayed by in
      situ hybridization. Expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h
      protein were detected by immunohischemistry and by Western blot. RESULTS: In situ
      hybridization showed that the expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma
      GCS-h mRNA in lung tissue were the lowest in group B and the comparison among
      groups showed statistical significant (all P < 0.01). Immunohistochemistry and
      Western blot indicated that the value of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS
      h protein in lung tissue were the lowest in group B, and expressed primarily in
      nucleus, the differences being statistically significant (all P < 0.01). There
      was positive correlation between PPAR-gamma and PGC-1. gamma-GCS-h mRNA also
      positively correlated between PPAR-gamma/PGC-1alpha and Nrf2 in nucleus, and the
      expression of Nrf2 was also positively correlated with PPAR-gamma/ PGC-1alpha.
      CONCLUSION: In acute asthmatic models induced by ovalbumin, the expressions of
      PPAR-alpha/PGC-1alpha and Nrf2/gamma-GCS-h were decreased, and PPARgamma/PGC
      1alpha could up-regulate the expressions of Nrf2/gamma-GCS-h to increase the
      antioxidant defense of tissues, thus being implicated that PPARgamma/PGC-1alpha
      might play important roles in the pathogenesis and prevention of asthma.

PMID- 21845881
TI  - [The effect of apigenin on reproductive axis in female rats].

PMID- 21845882
TI  - [Effects of ambroxol combined with low-dose heparin on TNF-alpha and IL-1beta in
      rabbits with acute lung injury].
AB  - OBJECTIVE: To investigate the intervention and mechanism of ambroxol combined
      with low-dose heparin on oxidative stress, TNF-alpha and IL-1beta in rabbits with
      acute lung injury (ALI). METHODS: Twenty-four healthy Japanese rabbits were
      randomly divided into three groups: (1) Normal saline control group (NC), (2)
      Oleic acid injury group (OA), (3) Ambroxol + low-dose heparin therapy group (AH).
      After the success of ALI model, AH group was injected ambroxol + low-dose
      heparin, while the NC group and OA group were injected the same dose of normal
      saline by the same method. Arterial oxygen tension (PaO2), tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta) at different time points were
      determined. The pathological manifestation of both side lungs was observed at the
      end of expeiment. The activity of glutathione peroxidase (GSH-Px), superoxide
      dismutase (SOD), xanthine oxidase (XO) and the content of malondialdehyde (MDA)
      in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate were tested.
      The apoptosis index was detected. The lung wet/dry (W/D) ratio was calculated.
      The pathological changes in lung tissue were observed by light microscopy, and
      the ultrastructural changes of lung tissue were observed by electron microscopy.
      RESULTS: (1) The instructive injury induced by ALI observed under electron
      microscope and light microscope and W/D was decreased significantly in AH group.
      (2) PaO2 was improved significantly in AH group, compared with that in OA group
      (P < 0.01). (3) The activity of GSH-Px and SOD in AH group increased
      significantly (P < 0.01 or P < 0.05) but the activity of XO and the content of
      MDA decreased significantly (P < 0.01), compared with those in OA group. (4)
      Except the content of IL-1beta in serum before treatment, the content of IL-1beta
      and TNF-alpha in serum, BALF, lung tissue homogenate of OA group increased
      significantly (P < 0.01), and those were obviously improved in AH group. (5)
      Apoptosis index (AI) in AH group decreased significantly (P < 0.01) compared with
      that in OA group. CONCLUSION: In ALI induced by OA, IL-1beta and TNF-alpha
      increases significantly and involved in the occurrence and development of ALI.
      Ambroxol combined with low-dose heparin can reduce lung cells oxidative stress to
      inhibit the release of IL-1beta and TNF-alpha, which play a role in the treatment
      of ALI.

PMID- 21845883
TI  - [The relationship between endoplasmic reticulum stress and its particular
      apoptosis way caspase-12 and apoptosis in renal cortex of diabetic rats].
AB  - OBJECTIVE: To investigate the expressions of 78-kDa glucose-regulated protein
      (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of
      diabetic rats. METHODS: Uninephrectomized Wistar rats were used to induce
      diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8
      weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell
      nuclear antigen (PCNA) were examined by immunohistochemistry. Flow cytometry was
      used to detect the levels of protein of GRP78 and Caspase-12. Apoptosis was
      evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick
      end labeling (TUNEL) and Flow cytometry. Serum creatinine, blood urea nitrogen
      and 24-hour urine protein excretion were checked. RESULTS: Compared with those in
      normal control group, the numbers of apoptosis and the expression of GRP78,
      Caspase-12 in glomerular and tubular cells were much higher in the diabetic
      kidneys at 8 weeks. There was no significant difference between group A and group
      B. CONCLUSION: Activation of endoplasmic reticulum stress may play an important
      role in the development of diabetic nephropathy.

PMID- 21845884
TI  - [A study on the effects of compound oil of semen spinosa, semen orientalis, and
      jasminoides on soothing nerves and improving mental capacities in mice].

PMID- 21845885
TI  - [Intragastric and subcutaneous administration of yolk antibodies against
      adipocyte plasma membrane proteins on growth and fat deposition in rats].
AB  - OBJECTIVE: To study the effects of different administrations of antibodies
      against adipocyte plasma membrane proteins on growth and fat deposition in rats.
      METHOD: Ninety six female SD rats that weighed approximately 140 g were allotted
      randomly into four groups which were given negitive control yolk and positive
      yolk containing antibody (IgY) against adipocyte plasma membrane (APM) proteins
      by intragastric administration (i.g.) and subcutaneous injection (s.c.)
      respectively. Rats were given 1 ml of yolk for every three days in i.g. groups.
      Rats were given 1 ml of yolk for 4 consecutive days, and the procedure was
      repeated after one month. The trial lasted for 75 days after which rats were
      slaughtered for carcass analysis and sampling. RESULTS: The body weight gain and
      food intake of rats were not different between treatment and control groups. In
      i.g. goups, positive yolk decreased mesemteric fat index, paramertrial fat index
      and perirenal fat index (P < 0.05), reduced serum triglycerides (P < 0.05) and
      increased serum free fatty acids (FFA) (P < 0.01), and also decreased serum
      leptin, insulin and TNF-alpha levels ( P < 0.01 or P < 0.05), but did not affect
      gastrocnemius muscle index and serum cholesterol. In s.c. groups, positive yolk
      increased gastrocnemius muscle index (P < 0.05), reduced serum triglycerides and
      serum leptin (P < 0.01), increased serum TNF-alpha (P < 0.05), but did not affect
      adipose tissue depots, serum FFA, cholesterol and insulin. CONCLUSION:
      Administration of yolk antibody against APM proteins could effectively improve
      body composition of rats, and the treatment by intragastric administration could
      give better effect than by subcutaneous injection.

PMID- 21845886
TI  - [Effects of salvia miltiorrhiza injection on gentamicin-induced expression of
      nitric oxide synthase isoforms in guinea pig cochlea].
AB  - OBJECTIVE: To investigate the effects of salvia miltiorrhiza injection (SM) on
      gentamicin (GM)-induced expression of nitric oxide synthase (NOS) isoforms in
      guinea pig cochlea, and to explore the protective mechanism of SM on GM-induced
      ototoxicity. METHODS: 40 guinea pigs were randomly assigned to 4 groups: control
      group, GM group, SM group and GM plus SM group. Expression of NOS isoforms in the
      guinea pig cochlea was detected by the SABC method of immunohistochemistry and
      microscope image analysis technique. Auditory threshold was tested by auditory
      brainstem response (ABR) measurement. RESULTS: Inducible NOS (iNOS/NOS II)
      expression and ABR threshold in GM plus SM group were both significantly declined
      as compared with those in GM group (P < 0.01). Moreover, change of iNOS
      expression was in high correlation with that of ABR threshold ([r] > 0.7, P <
      0.01). While expression of neuronal NOS (nNOS/NOS I) and endothelial NOS (eNOS /
      NOS III) showed no significant differences in all groups. CONCLUSION: SM had no
      effect on the expression of nNOS and eNOS, but could inhibit iNOS high-expression
      induced by GM to reduce excessive generation of NO, therefore SM could protect
      against GM ototoxicity.

PMID- 21845888
TI  - [Women boxing athletes' EMG of upper limbs and lumbar muscles in the training of
      air striking of straight punch].
AB  - OBJECTIVE: To study training effect of upper limbs and lumbar muscles in the
      proceed of air striking of straight punch by analyzing boxing athletes' changes
      of electromyogram (EMG). METHODS: We measured EMG of ten women boxing athletes'
      upper arm biceps (contractor muscle), upper arm triceps (antagonistic muscle),
      forearm flexor muscle (contractor muscle), forearm extensor muscle (antagonistic
      muscle), and lumbar muscles by ME6000 (Mega Electronics Ltd.). The stipulated
      exercise was to do air striking of straight punch with loads of 2.5 kg of
      dumbbell in the hand until exhausted. RESULTS: In the proceed of exercise-induce
      exhausted, the descend magnitude and speed of median frequency (MF) in upper limb
      antagonistic muscle exceeded to contracting muscle, moreover, the work percentage
      showed that contractor have done a larger percentage of work than antagonistic
      muscle. Compared with world champion's EMG, the majority of ordinary athletes'
      lumbar muscles MF revealed non-drop tendency, and the work percentage showed that
      lumbar muscles had a very little percentage of work. CONCLUSION: After comparing
      the EMG test index in upper limb and lumbar muscle of average boxing athletes
      with that of the world champion, we find the testees lack of the training of
      upper limb antagonistic muscle and lumbar muscle, and more trainings aimed at
      these muscles need to be taken.

PMID- 21845887
TI  - [Effect of a simulated He-O2 saturation dive to 65 msw on oxidative stress in
      humans].
AB  - OBJECTIVE: To investigate whether a simulated He-O2 saturation dive to 65 msw
      would affect oxidative balance in humans. METHODS: Seven divers participated in a
      simulated saturation dive to 0.75 MPa (65 msw). 24-h urine samples were collected
      twice before, twice during, and twice after the dive, then were analyzed for
      contents of superoxide dismutase (SOD), malondialdehyde (MDA), total amino acid
      (T-AA) and total anti-oxidant capacity (T-AOC). Meanwhile, total urine volume and
      body weight were measured. RESULTS: The content of T-AA was higher. (P < 0.05)
      than the base value in final decompression, but reverse to normal at one week
      after decompression. There were no changes in contents of SOD, MDA and T-AOC
      during and after the dive compared with their basic value. Total urine volume was
      lower (P < 0.05, vs basic value) at first day in chamber, then returned to
      normal. Body weight gradually increased after compression till the end of
      decompression (higher than basic value, P < 0.05). CONCLUSION: These data
      indicate that simulated saturation dive to 65 msw may not induce obvious
      oxidative damage, but it is necessary to monitor 24-h urine volume and oxidative
      sress by time in order to prevent from tissue injury.

PMID- 21845889
TI  - [Which direction, please, to the future?].

PMID- 21845890
TI  - [Congress of the International Council of Nurses in Malta. Recruiting Indians].

PMID- 21845891
TI  - [Medicine and nursing in the tension field of delegation. It all depends on
      internal solutions].

PMID- 21845892
TI  - [New course of studies "psychiatric nursing/psychological health". The entire
      spectrum in view].

PMID- 21845893
TI  - [Motivation and occupational chances of non certified caregivers. "I am only just
      a nurse's aide"...].

PMID- 21845894
TI  - [Uniform education in nursing. Prepared for every situation in life].

PMID- 21845895
TI  - [Advanced nursing practice - a path to better health care? The country needs
      specialists].

PMID- 21845896
TI  - [Quality indicators in geriatric nursing - method and design. It all depends on
      the outcome].

PMID- 21845897
TI  - [Compression in varicose ulcer. What is the effect of this measure?].

PMID- 21845898
TI  - [Personnel shortage in nursing. Innovative strategies to address the crisis].

PMID- 21845899
TI  - [Practicum in nursing and health management. Learning between studies and
      profession].

PMID- 21845900
TI  - [Benefit of the OSCE (objective structured clinical examination) method. Change
      in the examination culture].

PMID- 21845901
TI  - [The Clinical Learning Environment Supervision Scale. Evaluating the clinical
      learning environment].

PMID- 21845902
TI  - [A vote for generalized nursing education. One, two or three?].

PMID- 21845903
TI  - [Key indicator arthritis. Not just a disease of the elderly].

PMID- 21845904
TI  - [Challenge for routine nursing: implementing new standards. Between routine and
      quality].

PMID- 21845905
TI  - Steps in the analysis of synthetic biology.

PMID- 21845906
TI  - Learning health care systems and justice.

PMID- 21845907
TI  - Unreconcilable differences?

PMID- 21845908
TI  - Unreconcilable differences?

PMID- 21845909
TI  - Unreconcilable differences?

PMID- 21845910
TI  - Unreconcilable differences?

PMID- 21845911
TI  - Unreconcilable differences?

PMID- 21845912
TI  - A thousand little deaths.

PMID- 21845913
TI  - On regularity and regulation, health claims and hype.

PMID- 21845914
TI  - The legislative process is not fit for the abortion debate.

PMID- 21845915
TI  - Too much to ask?

PMID- 21845916
TI  - Case study. Too much to ask? Commentary.

PMID- 21845917
TI  - The ethics of synthetic biology: guiding principles for emerging technologies.

PMID- 21845918
TI  - Staying sober about science.

PMID- 21845919
TI  - Of microbes and men.

PMID- 21845920
TI  - The intrinsic scientific value of reprogramming life.

PMID- 21845921
TI  - Interests, identities, and synthetic biology.

PMID- 21845922
TI  - Can research and care be ethically integrated?
AB  - Medical ethics assumes a clear boundary between clinical research and clinical
      medicine: one produces knowledge for the benefit of future patients, while the
      other provides optimal care to individuals right now. It also assumes that the
      two cannot be integrated without sacrificing the needs of the current patient to
      those of future patients. But integration could allow us to provide better care
      to everyone, now and in the future.

PMID- 21845923
TI  - Dead rights.

PMID- 21845924
TI  - Medicine that's a little too personalized.

PMID- 21845925
TI  - A genetic instrumental variables analysis of the effects of prenatal smoking on
      birth weight: evidence from two samples.
AB  - There is a large literature showing the detrimental effects of prenatal smoking
      on birth and childhood health outcomes. It is somewhat unclear though, whether
      these effects are causal or reflect other characteristics and choices by mothers
      who choose to smoke that may also affect child health outcomes or biased
      reporting of smoking. In this paper we use genetic markers that predict smoking
      behaviors as instruments to address the endogeneity of smoking choices in the
      production of birth and childhood health outcomes. Our results indicate that
      prenatal smoking produces more dramatic declines in birth weight than estimates
      that ignore the endogeneity of prenatal smoking, which is consistent with
      previous studies with non-genetic instruments. We use data from two distinct
      samples from Norway and the United States with different measured instruments and
      find nearly identical results. The study provides a novel application that can be
      extended to study several behavioral impacts on health and social and economic
      outcomes.

PMID- 21845928
TI  - Integrating social science and genetics: news from the political front.
AB  - There has been growing interest in the use of genetic models to expand the
      understanding of political preferences, attitudes, and behaviors. Researchers in
      the social sciences have begun incorporating these models and have revealed that
      genetic differences account for individual differences in political beliefs,
      behaviors, and responses to the political environment. The first Integrating
      Genetics and the Social Sciences Conference, held at Boulder, Colorado in May of
      2010, brought together these researchers. As a result, we jointly review the last
      5 years of research in this area. In doing so, we explicate the methods,
      findings, and limitations of behavior genetic approaches, including twin designs,
      association studies, and genome-wide analyses, in their application toward
      exploring political preferences.

PMID- 21845927
TI  - Stressful life events and depression among adolescent twin pairs.
AB  - Using the twin pairs sample from the National Longitudinal Study ofAdolescent
      Health, we estimate bivariate Cholesky models for the influence of stressful life
      events (SLEs) on depressive symptoms. We show that depressive symptoms
      (h2Depression = .28) and dependent SLEs (events influenced by an individual's
      behavior) are both moderately heritable (h2SLE Dependent = .43). We find no
      evidence for the heritability of independent SLEs. Results from the bivariate
      Cholesky model suggest that roughly one-half of the correlation between
      depression and dependent SLEs is due to common genetic factors. Our findings
      suggest that attempts to characterize the causal effect of SLEs on mental health
      should limit their list of SLEs to those that are outside of the control of the
      individual.

PMID- 21845926
TI  - Inflammatory gene variants in the Tsimane, an indigenous Bolivian population with
      a high infectious load.
AB  - The Tsimane of lowland Bolivia are an indigenous forager-farmer population living
      under conditions resembling pre-industrial European populations, with high
      infectious morbidity, high infection and inflammation, and shortened life
      expectancy. Analysis of 917 persons ages 5 to 60+ showed that allele frequencies
      of 9 SNPs examined in the apolipoprotein E (apoE), C-reactive protein (CRP), and
      interleukin-6 (IL-6) genes differed from some European, African, and north Asian
      derived populations. The apoE2 allele was absent, whereas four SNPs related to
      CRP and IL-6 were monomorphic: CRP (rs1800947, rs3093061, and rs3093062) and IL-6
      (rs1800795). No significant differences in apoE, CRP, and IL-6 variants across
      age were found CRP levels were higher in carriers of two CRP proinflammatory
      SNPs, whereas they were lower in carriers of apoE4. Taken together the evidence
      for (1) different allele frequencies between the Tsimane and other populations
      and (2) the correlations of CRP and apoE alleles with blood CRP may suggest that
      these variants are under selection in response to a high infection environment.

PMID- 21845929
TI  - Social science methods for twins data: integrating causality, endowments, and
      heritability.
AB  - Twins have been extensively used in economics, sociology, and behavioral genetics
      to investigate the role of genetic endowments on a broad range of social,
      demographic, and economic outcomes. However, the focus in these literatures has
      been distinct.: The economic literature has been primarily concerned with the
      need to control for unobserved endowments--including as an important subset,
      genetic endowments--in analyses that attempt to establish the impact of one
      variable, often schooling, on a variety of economic, demographic, and health
      outcomes. Behavioral genetic analyses have mostly been concerned with decomposing
      the variation in the outcomes of interest into genetic, shared environmental, and
      non-shared environmental components, with recent multivariate analyses
      investigating the contributions of genes and the environment to the correlation
      and causation between variables. Despite the fact that twins studies and the
      recognition of the role of endowments are central to both of these literatures,
      they have mostly evolved independently. In this paper we develop formally the
      relationship between the economic and behavioral genetic approaches to the
      analyses of twins, and we develop an integrative approach that combines the
      identification of causal effects, which dominates the economic literature, with
      the decomposition of variances and covariances into genetic and environmental
      factors that are the primary goal of behavioral genetic approaches. We apply this
      integrative ACE-beta approach to an illustrative investigation of the impact of
      schooling on several demographic outcomes such as fertility and nuptiality and
      health.

PMID- 21845930
TI  - Checklist and pictorial key to fourth-instar larvae of mosquitoes (Diptera:
      Culicidae) of Saudi Arabia.
AB  - The Kingdom of Saudi Arabia includes fauna from three zoogeographic regions: the
      Afrotropical, Oriental, and Palaearctic regions. To study the mosquito (Diptera:
      Culicidae) fauna of these regions in Saudi Arabia, larval collections were made
      at 15 sites during 2005-2006. Thirty-three species representing nine genera were
      found. Six species, Anopheles culicifacies Giles s.l., Anopheles subpictus Grassi
      s.l., Culex arbieeni Salem, Culex simpsoni Theobald, Culex univittatus Theobald,
      and Ochlerotatus detritus Haliday are reported for the first time for Saudi
      Arabia. An annotated checklist and an illustrated key to the fourth-instar larvae
      of the 33 species are presented, along with some remarks about problematic
      species. Eleven species of genus Anopheles Meigen, five species of tribe Aedini,
      13 species of genus Culex L., two species of genus Culiseta Felt, one species of
      genus Lutzia Theobald, and one species of genus Uranotaenia Lynch Arribatlzaga
      were recorded during the study.

PMID- 21845931
TI  - Morphology and identification of first instars of African blow flies (Diptera:
      Calliphoridae) commonly of forensic importance.
AB  - Scanning electron microscopy images of the first instars of Calliphora
      croceipalpis Jaennicke, 1876; Chrysomya chloropyga (Wiedemann, 1818); Chrysomya
      marginalis (Wiedemann, 1830); and Chrysomya putoria (Wiedemann, 1830) (Diptera:
      Calliphoridae) are presented for the first time, and the following morphological
      structures are documented: pseudocephalon, antenna, maxillary palpus, facial
      mask, labial lobe, thoracic and abdominal spinulation, spiracular field,
      posterior spiracles, and anal pads. Light microscopy photographs and line
      illustrations are provided for the cephaloskeleton in lateral and ventral views,
      and the "ectostomal sclerite" and "chitinized teeth" of the cephaloskeleton are
      recognized as integral parts of the mouthhooks. New diagnostic features of the
      cephaloskeleton and the spinulation of the abdominal segments are described.
      These results allow refinement, clarification, and correction of earlier
      descriptions, which are reviewed. The relative taxonomic importance of various
      morphological characters of the first instars of necrophagous blow flies is
      discussed, and details of the cephaloskeleton and the spinulation of the
      abdominal segments are highlighted as the characters most useful for species
      identification. Finally, a key for identifying first instars of common African
      carrion blow flies is provided.

PMID- 21845932
TI  - Ectoparasites (Insecta and Acari) associated with bats in southeastern Brazil.
AB  - The result of a survey of ectoparasites infesting bats in southeastern Brazil is
      presented. Of 181 bats belonging to 16 species, 10 (34.1%) were infested by
      streblid flies (Streblidae), nine (33.5%) by spinturnicid mites (Spinturnicidae),
      and five (8.3%) by macronyssid mites (Macronyssidae). One species of the families
      Trombiculidae and Myobiidae was found. A total of 195 streblids, 178
      spinturnicids, and 76 macronyssids was collected. Paratrichobius longicrus was
      the most abundant bat fly species (50 specimens). The spinturnicid mite
      Periglischrus iheringi was the most abundant ectoparasite species (159 specimens)
      and was recorded on three different bat species; Radfordiella desmodi was the
      most numerous macronyssid (69 specimens).

PMID- 21845933
TI  - Description of nymphal stages of Periglischrus cubanus (Acari, Spinturnicidae),
      parasites from Erophylla sezekorni bombifrons (Chiroptera) from Puerto Rico with
      observations on the nymphal stages and host-parasite relationships within the
      genus Periglischrus.
AB  - The adults of Periglischrus cubanus were described by Dusbabek (1968). In this
      study, we describe the nymphal stages of this species and make some general
      observations on nymphal stages in the genus Periglischrus.

PMID- 21845934
TI  - Diversity of phlebotomine sand flies (Diptera: Psychodidae) in Ibitipoca State
      Park, Minas Gerais, Brazil.
AB  - Leishmaniasis is a complex of zoonotic diseases that are endemic to many
      Brazilian states. They are transmitted to the vertebrates by the bite of the
      hematophagous female sand fly (Diptera: Psychodidae) vectors. Despite the
      increasing occurrence of visceral and cutaneous leishmaniasis cases in large
      urban centers, their transmission continues to occur primarily in a wild
      environment and may be associated with professional activities, ecotourism
      activities, or both. This study investigates the ecological parameters of the
      sand flies present in Ibitipoca State Park, Minas Gerais, Brazil. During 2009,
      systematic collections of sand flies were made monthly using HP light traps
      installed at five sites, including three natural settings (a cave, riparian
      vegetation, and a rain forest), the tourist and researchers' accommodations, and
      a surrounding domestic livestock area. In total, 161 sand flies (seven species)
      were collected, the most abundant, particularly in the surrounding domestic
      livestock area, being Lutzomyia (Psychodopygus) lloydi (Antunes, 1937).
      Furthermore, a previously unidentified Lutzomyia (Sciopemyia) sp. was prevalent
      in the cave environment. There are no existing records of the occurrence of
      leishmaniasis in Ibitipoca State Park; however, the some species of the subgenus
      Psychodopygus are known vectors of Leishmania spp in Brazil. Hence, the presence
      of a species of this genus in areas surrounding the park may represent a risk to
      ecotourism and the local inhabitants. Our study shows the importance of regular
      monitoring of the various areas used by humans to determine the distribution and
      spread of sand fly vectors for preventive management to forestall potential risk
      to health and consequent effect on ecotourists.

PMID- 21845935
TI  - Distribution of Rhipicephalus (Boophilus) microplus and Rhipicephalus (Boophilus)
      annulatus (Acari: Ixodidae) infestations detected in the United States along the
      Texas/Mexico border.
AB  - Species identification and global positioning system coordinates of infestations
      of cattle fever ticks, Rhipicephalus (Boophilus) annulatus (Say) and
      Rhipicephalus (Boophilus) microplus (Canestrini), were determined for 790
      specimens submitted to the National Veterinary Services Laboratory between 1
      October 1999 and 30 September 2010. Cattle fever tick specimens obtained by
      personnel of the United States Department of Agriculture-Animal and Plant Health
      Inspection Service-Cattle Fever Tick Eradication Program from infested cattle and
      wildlife along the Texas/ Mexico border were submitted for identification, as
      required by the program. A geographic information system database was developed
      that incorporates location, collection, and infestation records. Submitted ticks
      came from 11 Texas counties and were comprised of 19.5% R. (B.) annulatus and
      80.5% R. (B.) microplus. Maps produced from this study locate and define the
      parapatric boundary between R. (B.) annulatus and R. (B.) microplus.

PMID- 21845936
TI  - Vital statistics of Triatominae (Hemiptera: Reduviidae) under laboratory
      conditions: III. Rhodnius neglectus.
AB  - Five cohorts of 100 eggs of Rhodnius neglectus Lent 1954 (Hemiptera Reduviidae)
      were reared simultaneously in the laboratory under constant conditions (26 +/- 1
      degrees C and 60 +/- 10% RH), with mortality and fecundity data recorded weekly.
      We calculated stage-specific developmental times, age-specific mortality and
      fecundity, stage-specific and total preadult mortality, and the intrinsic rate of
      natural increase (r0 = 0.21), the finite population growth rate (h = 1.23), the
      net reproductive rate (R0 = 314.24), and the generation time (T = 21.45 wk).
      Elasticity analysis showed that the dominant life-history traits determining
      lamda were the adult female survival, and the survival of instar V nymphs
      (molting into adult females). Adult females dominated the stage-specific
      reproductive value, and the egg stage dominated the stable stage distribution
      (SSD). The damping ratio (p = 1.11) suggests a relatively rapid period of
      recovery to a disturbed SSD. Results were compared with previous values from the
      literature and conform relatively well, considering that environmental conditions
      were not always the same. Compared with two other species of the same genus,
      Rhodnius neivai Lent 1953 and Rhodnius prolixus Stal 1859, R. neglectus ranked
      higher in fecundity (total eggs/ female /life) and in female longevity,
      intermediate in the intrinsic rate of natural increase (r0), and lower in
      developmental time and mortality. By fitting a logistic model of population
      growth to the density field values of a spontaneous colonization of two field
      experimental chicken coops we estimated the intrinsic rate of natural increase
      and carrying capacity parameters, and compared the former with our laboratory
      results.

PMID- 21845937
TI  - Diversity, geographic distribution, and habitat-specific variations of microbiota
      in natural populations of the chicken mite, Dermanyssus gallinae.
AB  - Dermanyssus gallinae is considered to be the most economically significant
      ectoparasite to affect egg-laying poultry in Europe. This mite can also act as a
      vector for a number of pathogens. The array of bacteria associated with D.
      gallinae mites could provide insight into the biology and population dynamics of
      arthropods, but at the present time little information is available. To
      understand the intra- and interpopulation diversity of its associated microbiota,
      we analyzed the whole internal bacterial community of natural populations of D.
      gallinae originating from two types of poultry farm habitats (standard and free
      range) in two regions of France (Brittany and the Rhone-Alpes). Total DNA was
      extracted from individual or pooled mites, and polymerase chain reaction temporal
      temperature gradient gel electrophoresis of 16S rRNA was then done to separate
      bacterial DNA fragments associated with the host arthropod. A large diversity of
      bacteria was detected, but principally firmicutes and gamma-Proteobacteria.
      Between-group analyses of temporal temperature gradient gel electrophoresis
      banding patterns revealed that bacterial populations clustered into categories
      according to their geographic origin and the habitat specifics of the farms. Some
      degree of stability of bacterial populations was observed within a specific time
      scale. These results suggest that environmental factors either recent (e.g.,
      poultry farming practices) or long-standing (e.g., geographic isolation) may
      affect the bacterial communities present in D. gallinae. Further knowledge of the
      microbiota associated with D. gallinae and its variation would indeed offer new
      perspectives for biological control methods to prevent the establishment,
      proliferation, and transmission of pathogenic bacteria.

PMID- 21845938
TI  - Population ecology and movement of the American cockroach (Dictyoptera:
      Blattidae) in sewers.
AB  - The population size, age-class structure, and movement of the American cockroach,
      Periplaneta americana (L.) (Dictyoptera: Blattidae), were studied in three sewers
      in Penang, Malaysia, from September 2008 to October 2009. Eighteen to 20 glass
      jar traps (two per manhole) were deployed for a 24-h period during each sampling
      occasion at each sewer. Adults and nymphs were active throughout the study
      period, with an average monthly trap catch of 57-97 adults and 79-99 nymphs. The
      mean proportions of adults and nymphs at the three sewers ranged from 0.47 to
      0.57. Of the 2177 male and 2717 female cockroaches marked and released over the
      three sewers, recapture rates were 29.4-45.8 and 30.8-47.0%, respectively. The
      proportion of marked males and females did not differ significantly from the
      proportion of recaptured marked males and females. However, the mean number of
      times a marked female was recaptured was significantly greater than that of
      males. Of the 783 males and 1,030 females that were marked and recaptured, 19.4
      and 24.7%, respectively, had moved between manholes, and significantly more
      females than males moved between manholes. Of the 406 recaptured marked adults
      that moved between manholes, 90.4% moved a distance of 2-20 m from their initial
      release site; one male moved 192 m, the longest distance recorded. Trap catch on
      each sampling occasion was positively correlated with daily mean temperature. The
      number of cockroach movements between manholes also was correlated with the mean
      daily minimum temperature.

PMID- 21845939
TI  - Biogeography of Triatoma sanguisuga (Hemiptera: Reduviidae) on two barrier
      islands off the coast of Georgia, United States.
AB  - Thirty-three Triatoma sanguisuga (LeConte) adults and nymphs were collected
      during June and July 2009, at five sites on Cumberland Island and two sites on
      Sapelo Island, Georgia, to assess genetic diversity within and between sites. All
      but three specimens were found in a peridomestic habitat. The entire length (699
      bp) of the cytochrome oxidase II mitochondrial gene was sequenced for each
      specimen. Twelve haplotypes were identified, nine from Cumberland Island and
      three from Sapelo Island. No haplotypes were shared between the two islands,
      indicating there is limited or no movement of gene flow between the islands.
      Phylogenetic relationships among the haplotypes were determined using both
      neighbor-joining and maximum parsimony analyses. The phylogenetic trees from both
      analyses were similar, with no distinct clades on either tree devoted to
      haplotypes from a single island. A haplotype network structure was determined
      using nested clade analysis, which produced two haplotype networks, one
      containing only specimens found on Cumberland Island. The second network included
      specimens from both islands, with the ancestral haplotype from Sapelo Island.
      This pilot study is the first to highlight triatomine populations in the
      southeastern United States using the cytochrome oxidase II mitochondrial gene,
      and indicates strong population structuring along the Georgia Coast.

PMID- 21845940
TI  - Cost of integrated vector control with improved sanitation and road
      infrastructure coupled with the use of slow-release Bacillus sphaericus granules
      in a tropical urban setting.
AB  - A field test of integrated vector control was conducted in a tropical urban
      setting with a combination of a floating, slow-release, granular formulation of
      Bacillus sphaericus and environmental engineering measures (renovation of roads,
      collective water pumps, and cesspool lids). The targets were Culex
      quinquefasciatus and Anopheles gambiae in the two biggest towns of Burkina Faso
      (West Africa). Within the intervention zone, water pumping stations were improved
      and the surroundings drained to prevent the accumulation of stagnant water. Roads
      were leveled and given either simple gutters on each side or a concrete channel
      on one side to drain runoff water. Garbage containers were installed to provide
      an alternative to the drainage channels for waste disposal. Septic tanks were
      modified so that they could be emptied without destroying their lid. This study
      showed that it is possible to implement mosquito control in a tropical urban
      environment with teams of young people rapidly trained to apply a biological
      larvicide without any tools other than an iron bar to lift cesspool lids.
      Environmental improvements were initially costly, but demanded little subsequent
      expenditure. Local inhabitants' committees were mobilized to provide people with
      information and monitor the efficacy of the measures. Compared with what people
      spent individually on mosquito prevention and malaria medicine, these measures
      were not expensive, but many expected the community to pay for them from existing
      taxes, e.g., for water treatment and disposal. The necessary funding and
      logistics require a municipal organization with neighborhood support, if the
      measures are to be effective.

PMID- 21845941
TI  - Acaricidal effect of essential oils from Lippia graveolens (Lamiales:
      Verbenaceae), Rosmarinus officinalis (Lamiales: Lamiaceae), and Allium sativum
      (Liliales: Liliaceae) against Rhipicephalus (Boophilus) microplus (Acari:
      Ixodidae).
AB  - Acaricidal effects of three essential oils extracted from Mexican oregano leaves
      (Lippia graveolens Kunth), rosemary leaves (Rosmarinus officinalis L.), and
      garlic bulbs (Allium sativum L.) on 10-d-old Rhipicephalus (Boophilus) microplus
      (Canestrini) tick larvae were evaluated by using the larval packet test bioassay.
      Serial dilutions of the three essential oils were tested from a starting
      concentration of 20 to 1.25%. Results showed that both Mexican oregano and garlic
      essential oils had very similar activity, producing high mortality (90-100%) in
      all tested concentrations on 10-d-old R. microplus tick larvae. Rosemary
      essential oil produced >85% larval mortality at the higher concentrations (10 and
      20%), but the effect decreased noticeably to 40% at an oil concentration of 5%,
      and mortality was absent at 2.5 and 1.25% of the essential oil concentration.
      Chemical composition of the essential oils was elucidated by gas chromatography
      mass spectrometry analyses. Mexican oregano essential oil included thymol
      (24.59%), carvacrol (24.54%), p-cymene (13.6%), and y-terpinene (7.43%) as its
      main compounds, whereas rosemary essential oil was rich in a-pinene (31.07%),
      verbenone (15.26%), and 1,8-cineol (14.2%), and garlic essential oil was rich in
      diallyl trisulfide (33.57%), diallyl disulfide (30.93%), and methyl allyl
      trisulfide (11.28%). These results suggest that Mexican oregano and garlic
      essential oils merit further investigation as components of alternative
      approaches for R. microplus tick control.

PMID- 21845942
TI  - Susceptibility of sylvatic Triatoma infestans from Andeans valleys of Bolivia to
      deltamethrin and fipronil.
AB  - We describe the susceptibility to deltamethrin and fipronil of four sylvatic
      Triatoma infestans populations from the Andean valleys of Bolivia. Fifty percent
      lethal doses were determined from topical application of insecticide on first
      instars, and mortality was assessed after 24 h for deltamethrin and 48 h for
      fipronil. In comparison with a reference strain from Argentina, the Bolivian
      populations showed deltamethrin 50 percent lethal dose ratios ranging from 1.9 to
      17.4. In the case of fipronil, an insecticide never used for control of T.
      infestans, the Bolivian populations showed even higher variation in toxic
      response, with relative susceptibilities ranging from 0.5 to 139.2. However,
      although the sylvatic T infestans toxicological profiles differ from each other
      and from those of the domiciliary population studied in this work, there were no
      significant differences in the activities of P450 mono-oxygenases and pyrethroid
      esterases between the reference strain and the studied populations.

PMID- 21845943
TI  - Identification of mosquito biting deterrent constituents from the Indian folk
      remedy plant Jatropha curcas.
AB  - An investigation of the Indian folk remedy plant Jatropha curcas L., was
      performed to identify the constituents responsible for the mosquito biting
      deterrent activity of the oil. J. curcas seed oil is burned in oil lamps in India
      and parts of Africa to repel biting insects, primarily mosquitoes. The seed oil
      was thoroughly analyzed by 1H NMR, 13C NMR, high-performance liquid
      chromatography-refractive index, and gas chromatography-flame ionization
      detection to identify the constituents in the oil. Identified constituents, both
      free fatty acids and triglycerides, were evaluated for activity in Aedes aegypti
      (L.) (Diptera: Culicidae) biting deterrent assays. Furthermore, an oil
      condensation trap was used to demonstrate that free fatty acids or triglycerides
      are partially volatilized during the combustion process. These compounds were
      found to be responsible for the biting deterrency of the burned oil.
      Specifically, oleic, palmitic, linoleic, and stearic acids were all active at 25
      nmol/cm2 above that of solvent control in Ae. aegypti biting deterrent assays.
      Oleic, palmitic, and linoleic acids were all more active than stearic acid in the
      same bioassay. Evaluation of the triglycerides containing each of these fatty
      acids revealed that tripalmitin, tristearin, trilinolein, and triolein all
      demonstrated significant activity above a solvent control at 10 microg/cm2,
      whereas tripalmitin was the most active. Due to literature reports suggesting
      larvicidal activity of the oil, J. curcas seed oil and its free fatty acid
      constituents also were evaluated against 1-d-old Ae. aegypti larvae up to 500
      ppm. Oleic acid was the only fatty acid having larvicidal activity against 1-d
      old Ae. aegypti larvae, with an LD50 of 47.9 ppm.

PMID- 21845944
TI  - Toxicity of Brazilian plant seed extracts to two strains of Aedes aegypti
      (Diptera: Culicidae) and nontarget animals.
AB  - Seed ethanolic extracts of 21 Brazilian plants were evaluated for ovicidal,
      larvicidal, and pupicidal activities against insecticide-susceptible (SS) and
      field-collected (FC) strains of Aedes aegypti (L.) (Diptera: Culicidae), as well
      as for their effects on nontarget organisms. Myracrodruon urundeuva Fr. Allemao
      extract was highly toxic to both mosquito strains. Schinopsis brasiliensis Engler
      extract showed low toxicity and was 38-68 times less toxic to Ae. aegypti larvae
      than was M. urundeuva extract. The pupicidal activity (LC50) of 14 plant seed
      extracts ranged between 9 and 433/g/ml, and toxicities were comparable to both
      mosquito strains. Piptadenia moniliformis Benth. and Luetzelburgia auriculata
      (Allemao) Ducke extracts showed the highest activities against pupae of FC and SS
      strains. None of the extracts showed 100% ovicidal activity. In addition, the
      active extracts did not show high acute toxicity to mice (LD50 > 1.5 g/kg),
      except that of Enterolobium contortisiliquum (Vell.) Morong. Most of the active
      extracts exhibited low toxicity against brine shrimp (Artemia sp.) nauplii. The
      extracts of M. urundeuva, P. moniliformis, and L. auriculata are promising
      sources of recognized classes of insecticidal compounds with good selectivity
      against immature stages of Ae. aegypti.

PMID- 21845945
TI  - Avian hosts of Ixodes pacificus (Acari: Ixodidae) and the detection of Borrelia
      burgdorferi in larvae feeding on the Oregon junco.
AB  - Larval and nymphal western blacklegged tick, Ixodes pacificus Cooley & Kohls
      (Acari: Ixodidae), were collected from birds, rodents, and lizards at Quail Ridge
      Reserve located in Napa County in northwestern California. Species from three
      vertebrate classes were sampled simultaneously from two transects during two
      consecutive spring seasons. Feeding larval and nymphal ticks were removed and
      preserved for counting, examination and testing for the presence of Borrelia
      burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner. Mean infestations with
      I. pacificus subadults on lizards were 10.0, on birds 2.9, and on rodents 1.3. I.
      pacificus larvae (204) collected from 10 avian species and (215) collected from
      two rodent species were tested for the presence of B. burgdorferi s.s. via real
      time polymerase chain reaction. Three B. burgdorferi-infected larvae were taken
      from two Junco hyemalis and two infected larvae from one Neotoma fuscipes Baird.
      This is the detection of B. burgdorferi ss in an Ixodes pacificus larvae feeding
      on a Junco hyemalis L., [corrected] in western North America.

PMID- 21845946
TI  - Molting success of Ixodes scapularis varies among individual blood meal hosts and
      species.
AB  - The blacklegged tick (Ixodes scapularis) is an important vector of emerging human
      pathogens. It has three blood-feeding stages, as follows: larva, nymph, and
      adult. Owing to inefficient transovarial transmission, at least for the Lyme
      disease agent (Borrelia burgdorferi), larval ticks rarely hatch infected, but
      they can acquire infection during their larval blood meal. Nymphal ticks are
      primarily responsible for transmitting pathogens to hosts, including humans. The
      transition from uninfected host-seeking larva to infectious host-seeking nymph is
      therefore a key aspect of human risk of infection. It can be divided into a
      series of steps, as follows: finding a host, taking a blood meal, becoming
      infected, molting, and overwintering. The chance of succeeding in each of these
      steps may depend on the species identity of the blood meal host. We used a
      Bayesian method to estimate the molting success of larval I. scapularis collected
      from four commonly parasitized species of birds and eight commonly parasitized
      small and mid-sized mammals found in the forests of Dutchess County, New York. We
      show that molting success varies substantially among host species; white-footed
      mice, veeries, and gray catbirds support particularly high molting success,
      whereas ticks feeding on short-tailed shrews, robins, and wood thrushes were less
      successful. We also show that larval molting success varies substantially between
      individual blood meal hosts, and that this intraspecific variability is much
      higher in some species than in others. The causes of both inter- and
      intraspecific variation in molting success remain to be determined.

PMID- 21845947
TI  - Meteorological and hydrological influences on the spatial and temporal prevalence
      of West Nile virus in Culex mosquitoes, Suffolk County, New York.
AB  - The factors determining the spatial and temporal distribution of West Nile virus
      (family Flaviviridae, genus Flavivirus, WNV) activity are not well understood.
      Here, we explore the effects of hydrological and meteorological conditions on WNV
      infection among Culex genus mosquitoes collected during 2001-2009 in Suffolk
      County, Long Island, NY. We show that WNV infection rates in assayed pools of
      Culex mosquitoes are associated in both space and time with hydrological and
      meteorological variability. Specifically, wet winter, warm and wet spring
      conditions, and dry summer conditions are associated with the increased local
      prevalence of WNV among Culex mosquitoes during summer and fall. These findings
      indicate that within Suffolk County, and for a given year, areas at risk for
      heightened WNV activity may be identified in advance by using hydrology model
      estimates of land surface wetness and observed meteorological conditions.

PMID- 21845948
TI  - Assessment of Stomoxys calcitrans (Diptera: Muscidae) as a vector of porcine
      reproductive and respiratory syndrome virus.
AB  - Porcine Reproductive and respiratory syndrome (PRRS) is a globally significant
      swine disease caused by an arterivirus. The virus replicates in alveolar
      macrophages of infected pigs, resulting in pneumonia in growing pigs and late
      term abortions in sows. Outbreaks occur on disparate farms within an area despite
      biosecurity measures, suggesting mechanical transport by arthropods. We
      investigated the vector potential of stable flies, Stomoxys calcitrans (L.)
      (Diptera: Muscidae), in the transmission of porcine reproductive and respiratory
      syndrome virus (family Arteriviridae, genus Arterivirus, PRRSV) under laboratory
      conditions. Stable flies were collected around PRRS-negative boar stud barns in
      North Carolina and tested for presence of the virus. Stable flies were collected
      on alsynite traps placed near the exhaust fan of the close-sided tunnel
      ventilated buildings, suggesting blood seeking flies are attracted by olfactory
      cues. No flies were positive for PRRSV. We assessed transmission of the virus
      through an infective bite by feeding laboratory reared stable flies on blood
      containing virus and transferring them to naive pigs for subsequent bloodmeals.
      Transmission of the virus to naive pigs by infective bites failed in all
      attempts. The volume of blood contained within the closed mouthparts of the
      stable fly seems to be insufficient to deliver an infective dose of the virus.
      Stable flies are unlikely to transmit PRRSV from one pig to another while blood
      feeding. The fate of the virus after a bloodmeal remains to be determined.

PMID- 21845949
TI  - Transmission efficiency of Francisella tularensis by adult american dog ticks
      (Acari: Ixodidae).
AB  - The American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), has been
      implicated as a potential bridging vector to humans of Francisella tularensis,
      the etiological agent of tularemia. Since the initial studies evaluating vector
      competency of D. variabilis were conducted, F. tularensis has been subdivided
      into subspecies and clades that differ in their geographical distribution in the
      United States and in the severity of infections caused in humans. Here, we
      demonstrate that D. variabilis nymphs efficiently acquire, transtadially
      maintain, and transmit each of the strains tested (clades A1b and A2, and type
      B). Transmission efficiency by adult females was similarly high among infection
      groups and ranged from 58% for type B to 89% for A2 infections. In addition, we
      demonstrated that transmission can occur shortly after tick attachment. These
      findings support the concept that D. variabilis adults may play a significant
      role in epizootic transmission of F. tularensis, and as a bridging vector to
      humans.

PMID- 21845950
TI  - Acquisition and subsequent transmission of Borrelia hermsii by the soft tick
      Ornithodoros hermsi.
AB  - Tick-borne relapsing fever is caused by spirochetes within the genus Borrelia.
      The hallmark of this disease is recurrent febrile episodes and high spirochete
      densities in mammalian blood resulting from immune evasion. Between episodes of
      spirochetemia when bacterial densities are low, it is unknown whether ticks can
      acquire the spirochetes, become colonized by the bacteria, and subsequently
      transmit the bacteria once they feed again. We addressed these questions by
      feeding ticks, Omnithodoros hermsi Wheeler (Acari: Argasidae),daily on an
      infected mouse during low andhigh levels of spirochete infections. This study
      demonstrates that spirochete acquisition by the tick vector can occur during low
      levels of mammalian infection and that once a spirochetemic threshold is attained
      within the blood, nearly 100% of ticks become colonized by Borrelia hermsii.

PMID- 21845951
TI  - Test of recrudescence hypothesis for overwintering of eastern equine
      encephalomyelitis virus in gray catbirds.
AB  - Eastern equine encephalitis virus (EEEV; family Togaviridae, genus Alphavirus)
      epizootics are infrequent, but they can lead to high mortality in infected horses
      and humans. Despite the importance of EEEV to human and animal health, little is
      known about how the virus overwinters and reinitiates transmission each spring,
      particularly in temperate regions where infected adult mosquitoes are unlikely to
      survive through the winter. One hypothesis to explain the mechanism by which this
      virus persists from year to year is the spring recrudescence of latent virus in
      avian reservoir hosts. In this study, we tested the recrudescence hypothesis with
      gray catbirds (Dumatella carolinensis) captured in northern Ohio (July-August
      2007). Birds were experimentally infected with EEEV on 1 October 2007. In January
      2008, they were then exposed to exogenous testosterone and/or extended
      photoperiod to initiate reactivation of latent EEEV infection. All birds became
      viremic with EEEV, with mean viremia of 6.0 log10 plaque-forming units/ml serum
      occurring at 1 d postinoculation. One male in the testosterone, long-day
      treatment group had EEEV viral RNA in a cloacal swab collected on 18 January
      2008. Otherwise, no other catbirds exhibited reactivated infections in cloacal
      swabs or blood. Antibody titers fluctuated over the course of the study, with
      lowest titers observed in January 2008, which corresponded with the lowest mean
      weight of the birds. No EEEV viral RNA was detected in the blood, kidney, spleen,
      brain, liver, and lower intestine upon necropsy at 19 wk postinfection.

PMID- 21845952
TI  - Blood meal identification and prevalence of avian malaria parasite in mosquitoes
      collected at Kushiro wetland, a subarctic zone of Japan.
AB  - In Japan, the prevalence of avian Plasmodium in birds and mosquitoes has been
      partially examined in the temperate and subtropical zones; however, mosquitoes in
      the Japanese subarctic zone have not been adequately investigated. In this study,
      mosquito collections and avian Plasmodium detections from the mosquito samples
      were carried out to demonstrate the avian Plasmodium transmission between vector
      mosquitoes and birds inhabiting in Kushiro Wetland, subarctic zone of Japan. A
      total of 5657 unfed mosquitoes from 18 species and 320 blood-fed mosquitoes from
      eight species was collected in summer 2008, 2009, and 2010. Three Aedes esoensis
      that fed on Hokkaido Sika Deer and one unfed Culex pipiens group were found to be
      positive for avian Plasmodium by polymerase chain reaction. This is the first
      report of the detection of avian Plasmodium DNA from mosquitoes distributing in
      the subarctic zone of Japan. The blood meals were successfully identified to
      captive or wild animals, including seven mammalian species, four bird species,
      and one amphibian species. These results indicated that infected birds with avian
      Plasmodium inhabited and direct contacts occurred between the infected birds and
      mosquitoes in Kushiro Wetland, Hokkaido, Japan.

PMID- 21845953
TI  - Assessing the use of diurnal resting shelters by Culiseta melanura (Diptera:
      Culicidae).
AB  - Twenty resting shelters were set on the edge of a known Culiseta breeding habitat
      in four groups of five to support a 4 x 4 Latin square field experiment.
      Collection times were 0900, 1100, 1300, and 1500 hours and systematically rotated
      for the order by which each group of five boxes was collected. Mosquitoes were
      collected from resting shelters by chloroform anesthetization. Collections were
      identified to species, sex, and physiological status of the females (nonblooded
      or blood-fed and gravid). More than 77% of the mosquitoes collected were Culiseta
      melanura (Coquillett). Analyses included means and SE for total collections and
      shelter-day (number collected per units) and means comparison by t-test and
      general linear model with Student-Newman-Keuls or least significant differences
      means tests for replicate, group, time, and interactions of time and group. There
      were few significant differences among or between shelter-day means but more
      blood-fed and gravid female Cs. melanura were collected at 1300 hours than any
      other time. Results confirm the effectiveness of resting shelters in a
      surveillance program for Cs. melanura, demonstrate the flexibility of resting
      shelters as a surveillance tool, and suggest that Cs. melanura will move to more
      acceptable resting sites during daylight.

PMID- 21845954
TI  - Thermal sensitivity of Aedes aegypti from Australia: empirical data and
      prediction of effects on distribution.
AB  - An understanding of physiological sensitivity to temperature and its variability
      is important for predicting habitat suitability for disease vectors under
      different climatic regimes. In this study, we characterized the thermal
      sensitivity of larval developmental rates and survival in several Australian
      mainland populations of the dengue virus vector Aedes aegypti. Males developed
      more rapidly than females, but there were no differences among populations for
      development time or survival despite previously demonstrated genetic
      differentiation for neutral markers. Optimal development and survival
      temperatures were 37 degrees C and 25 degrees C, respectively. The values for
      maximal development and survival were similar to standard functions used in the
      container inhabiting simulation (CIMSIM) model for predicting population dynamics
      ofAe. aegypti populations, but CIMSIM assumed a lower optimal temperature. Heat
      stress experiments indicated that larvae could withstand water temperatures up to
      44 degrees C regardless of the rate at which temperature was increased. Results
      from development time measured under constant temperatures could predict
      development time under fluctuating conditions, whereas CIMSIM predicted faster
      rates of development. This difference acts to reduce the predicted potential
      number of generations of Ae. aegypti per year in Australia, although it does not
      influence its predicted distribution, which depends critically on the nature of
      the aquatic breeding sites.

PMID- 21845955
TI  - Human-induced expanded distribution of Anopheles plumbeus, experimental vector of
      West Nile virus and a potential vector of human malaria in Belgium.
AB  - For the majority of native species, human-created habitats provide a hostile
      environment that prevents their colonization. However, if the conditions
      encountered in this novel environment are part of the fundamental niche of a
      particular species, these low competitive environments may allow strong
      population expansion of even rare and stenotopic species. If these species are
      potentially harmful to humans, such anthropogenic habitat alterations may impose
      strong risks for human health. Here, we report on a recent and severe outbreak of
      the viciously biting and day-active mosquito Anopheles plumbeus Stephens, 1828,
      that is caused by a habitat shift toward human-created habitats. Although
      historic data indicate that the species was previously reported to be rare in
      Belgium and confined to natural forest habitats, more recent data indicate a
      strong population expansion all over Belgium and severe nuisance at a local
      scale. We show that these outbreaks can be explained by a recent larval habitat
      shift of this species from tree-holes in forests to large manure collecting pits
      of abandoned and uncleaned pig stables. Further surveys of the colonization and
      detection of other potential larval breeding places of this mosquito in this
      artificial environment are of particular importance for human health because the
      species is known as a experimental vector of West Nile virus and a potential
      vector of human malaria.

PMID- 21845956
TI  - Secondary kill effect of deltamethrin on Triatoma infestans.
AB  - Control of the Chagas disease vector, Triatoma infestans, relies on the
      application of pyrethroid insecticides, especially deltamethrin. We performed
      laboratory studies to determine whether a T. infestans nymph that comes into
      contact with a deltamethrin-treated surface horizontally transfers the
      insecticide to subsequent triatomines. We found that a triatomine that walks on a
      deltamethrin-treated surface for a short period of time has the ability to
      transport the insecticide in concentrations sufficient to kill other triatomines
      with which it comes into contact. The effect was limited to high-density
      environments, and mortality as a result of secondary exposure was greater among
      second-instar nymphs compared with fifth-instar nymphs. Our results suggest that
      deltamethrin could be killing triatomines through both direct and indirect
      contact, although it remains unclear whether the phenomenon occurs in natural
      conditions.

PMID- 21845957
TI  - A case study of Megaselia scalaris (Diptera: Phoridae) causing ocular myiasis in
      a western hognose snake.
AB  - Late instar larvae of the scuttle fly, Megaselia scalaris Loew, were found near
      the right eye of a live captive-reared western hognose snake, Heterodon nasicus
      Baird and Girard. Dissection and removal of the snake's dorsal cranial bones
      revealed tissue degradation of the infected eye, the optic nerve, and the brain
      case; we suggest that these factors contributed to the death of this snake. This
      case study further demonstrates the opportunistic behavior of M. scalaris.

PMID- 21845958
TI  - Multiplex polymerase chain reaction diagnostics of bed bug (Hemiptera:
      Cimicidae).
AB  - Cimex lectularius L. (Hemiptera: Cimicidae) is a widespread blood feeding pest of
      humans around the world, including North America, and has recently undergone a
      resurgence. A molecular diagnostic technique applying multiplex polymerase chain
      reaction (PCR) was developed to distinguish bed bug eggs, leg fragments, and
      degraded samples from other arthropods that frequently occur in human dwellings.
      A 410-428-bp region of the mitochondrial DNA 16S rRNA gene was used. To design C.
      lectularius-specific PCR primers, DNA sequences of various bed bug samples from
      the United States, Canada, and Australia, along with sequences of other Cimicidae
      and arthropods that often occur in dwellings, were considered. Based on DNA
      sequence variation, one reverse PCR primer specific for C. lectularius was
      identified. Multiplex PCR using three primers will yield a 417- and 140-bp
      amplicon for C. lectularius and a single 410-428-bp amplicon for other taxa. This
      assay was successful in identifying C. lectularius eggs, leg fragments, and
      degraded samples. This technique should provide a reliable, quick, and economical
      technique for identifying C. lectularius, when morphological identification is
      not possible.

PMID- 21845959
TI  - Behavioral observations and sound recordings of free-flight mating swarms of Ae.
      Aegypti (Diptera: Culicidae) in Thailand.
AB  - Sound plays an important role in the mating behavior of mosquitoes, including
      Aedes aegypti (L). Males orient to the fundamental wing beat frequency of
      females, and both sexes actively modulate their flight tone before mating to
      converge at harmonic frequencies. The majority of studies on mosquito mating
      acoustics have been conducted in the laboratory using tethered individuals. In
      this study, we present the first free-flight recording of naturally forming Ae.
      aegypti swarms in Thailand. We describe mating behaviors and present results on
      the flight tone frequency and dynamics of wild pairs in free flight. To assess
      the importance of these behaviors in vector control programs, especially those
      using genetically modified mosquitoes, it will be critical to use methods, such
      as those described in this work, to measure mosquito mating behaviors in the
      field.

PMID- 21845960
TI  - Identification and validation of reference genes for quantitative real-time
      polymerase chain reaction in Cimex lectularius.
AB  - Quantitative real-time polymerase chain reaction (qRT-PCR) has emerged as robust
      methodology for gene expression studies, but reference genes are crucial for
      accurate normalization. Commonly used reference genes are housekeeping genes that
      are thought to be nonregulated; however, their expression can be unstable across
      different experimental conditions. We report the identification and validation of
      suitable reference genes in the bed bug, Cimex lectularius, by using qRT-PCR. The
      expression stability of eight reference genes in different tissues (abdominal
      cuticle, midgut, Malpighian tubules, and ovary) and developmental stages (early
      instar nymphs, late instar nymphs, and adults) of pesticide-susceptible and
      pesticide-exposed C. lectularius were analyzed using geNorm, NormFinder, and
      BestKeeper. Overall expression analysis of the eight reference genes revealed
      significant variation among samples, indicating the necessity of validating
      suitable reference genes for accurate quantification of mRNA transcripts.
      Ribosomal protein (RPL18) exhibited the most stable gene expression across all
      the tissue and developmental-stage samples; a-tubulin revealed the least
      stability across all of the samples examined. Thus, we recommend RPL18 as a
      suitable reference gene for normalization in gene expression studies of C.
      lectularius.

PMID- 21845961
TI  - Combining piperonyl butoxide and dinotefuran restores the efficacy of
      deltamethrin mosquito nets against resistant Anopheles gambiae (Diptera:
      Culicidae).
AB  - One strategy suggested for the management of mosquito insecticide resistance
      consists of combining a pyrethroid with an insecticide that has a different mode
      of action. To restore the efficacy of deltamethrin (pyrethroid) against
      pyrethroid-resistant strain of Anopheles gambiae Giles (VKPR: homozygous Kdr),
      deltamethrin was combined with the neonicotinoid insecticide dinotefuran and
      piperonyl butoxide (PBO). Bednets impregnated with deltamethrin, dinotefuran, and
      PBO alone and in combination were tested in the laboratory. Knockdown (KD) and
      mortality were measured using WHO cone tests on susceptible and pyrethroid
      resistant adult mosquitoes. The combination of deltamethrin and PBO was
      synergistic against resistant female An. gambiae (58.2% mortality). Both
      mortality and knockdown time (KDt(50/95) values) of the tricomponent mixture on
      the VKPR strain were similar to the insecticidal activity of deltamethrin on the
      pyrethroid-susceptible KIS strain (98.8 and 100% mortality, respectively). The
      three-compound mixture of deltamethrin + PBO + dinotefuran showed an insecticidal
      efficacy greater than the deltamethrin + PBO mixture to the extent of completely
      restoring the efficacy of deltamethrin on pyrethroid-resistant An. gambiae.

PMID- 21845962
TI  - Host-feeding patterns of native Culex pipiens and invasive Aedes albopictus
      mosquitoes (Diptera: Culicidae) in urban zones from Barcelona, Spain.
AB  - The feeding patterns of haematophagous arthropods are of major importance in the
      amplification and transmission of infectious disease agents to vertebrate hosts,
      including humans. The establishment of new vector populations in nonnative range
      might alter transmission networks. The Asian tiger mosquito Aedes albopictus
      (Skuse) represents an example of how an invasive species can alter the risk of
      viral transmission to humans. Blood meal molecular identification from two
      sympatric mosquito species (the invasive Ae. albopictus and the native Culex
      pipiens) was carried out by polymerase chain reaction-based methods. Samples were
      collected in Barcelona metropolitan area, Spain, from June to October 2009 as
      part of a monitoring-control program. Blood meals were identified to the species
      level in 30 Ae. albopictus and 43 Cx. pipiens. Ae. albopictus acquired blood
      exclusively from human hosts (100%), whereas Cx. pipiens fed on a diversity of
      avian and mammalian hosts, including 35.7% of blood meals from humans. Based on
      mosquito diet, our results suggest that the Ae. albopictus invasion in Spain
      might increase the risk of virus transmission to humans and could support local
      outbreaks of imported tropical viruses such as dengue and chikungunya. However,
      in the studied area, the presence of this invasive species would have a
      negligible effect on the transmission of zoonotic agents such as West Nile virus.
      However, Cx. pipiens could amplify and transmit West Nile virus, but avian
      contribution to its diet was lower than that reported in North America. Feeding
      patterns of these mosquito species may help to understand the flavivirus
      outbreaks recently reported in southwestern Europe.

PMID- 21845963
TI  - Medical discoveries in the ghettos: the anti-typhus battle.

PMID- 21845964
TI  - Conspiracy in Paris, November 1938: medical fraud as pretext for the
      Kristallnacht pogrom.
AB  - This medical history essay claims that a medical fraud was committed by the
      authorities and was used as a pretext for the November 1938 anti-jewish
      Kristallnacht pogrom throughout the Third Reich. The suggested conspiracy covered
      up the real cause of death of the German Embassy's secretary in Paris. Baron
      Ernst vom Rath had been shot by a Jewish teenager who was frantic because of the
      plight of his family. A surgical analysis of the victim's injuries, and of the
      medical attention he received, suggests the likelihood of medical malpractice
      which led to his preventable demise.

PMID- 21845965
TI  - Albert Uffenheimer: pediatrician and public health advocate before Nazi rule.
AB  - Before World War lI the number of Jewish physicians practicing pediatric medicine
      in Germany was very high, but soon after the National Socialists came to power
      the discrimination against Jewish physicians began. One of them, Dr. Albert
      Uffenheimer, serves as a moving example of this persecution. Dr. Uffenheimer was
      engaged in the fight against the high infant mortality and was instrumental in
      the creation of public health facilities for counselling parents. In 1925 he
      became Director of the Children's Hospital in Magdeburg and within a short time
      had improved the medical care of both infants and mothers. In April 1933, two
      months after the Nazi takeover, he was dismissed from his post at the Children's
      Hospital in Magdeburg and immigrated to the United States. Dr. Uffenheimer was a
      pioneer in the field of public health before such new concepts were recognized as
      important. As such he should be remembered as a founding father of social
      pediatrics in Germany.

PMID- 21845966
TI  - Anti-DNA activity in systemic lupus erythematosus.

PMID- 21845967
TI  - Characteristics of rotavirus gastroenteritis in hospitalized children in Israel.
AB  - BACKGROUND: Diarrhea is a leading cause of child mortality worldwide. Rotavirus
      is one of the most common causes of severe diarrhea and dehydration in children.
      OBJECTIVES: To compare the demographic, clinical and laboratory characteristics
      of patients with rotavirus gastroenteritis to those with other causes of
      gastroenteritis. METHODS: The medical records of children aged 0-18 years
      hospitalized with acute gastroenteritis in our facility between 1 January 2004
      and 31 March 2006 were retrieved. Patients with rotavirus gastroenteritis were
      compared with patients who were rotavirus negative. RESULTS: The study group
      comprised 533 patients; 202 tested positive for rotavirus and 331 tested
      negative. Compared to patients with rotavirus-negative gastroenteritis, patients
      with rotavirus-positive gastroenteritis had a higher incidence of vomiting
      (185/202 vs. 212/331, 92% vs. 64%, P < 0.001), lethargy (67/202 vs. 51/331, 33%
      vs. 15%, P < 0.001), and dehydration (81/202 vs. 78/331, 40% vs. 24%, P < 0.001).
      The need for intravenous rehydration therapy and the duration of hospitalization
      were higher in patients with rotavirus gastroenteritis. CONCLUSIONS: Vomiting and
      dehydration are more common in hospitalized children with rotavirus
      gastroenteritis than in children with gastroenteritis due to other causes.

PMID- 21845968
TI  - In vivo oxidation, platelet activation and simultaneous occurrence of natural
      immunity in atherosclerosis-prone mice.
AB  - BACKGROUND: Several murine models are susceptible to atherosclerosis, such as low
      density-lipoprotein receptor-deficient (LDLR-/-) and apolipoprotein E-deficient
      (apoE-/-) mice, and are used for studying pathophysiological mechanisms.
      Atherosclerotic lesions in the aortic valve and thoracic/abdominal aorta are
      commonly associated with hyperlipidemia. We recently demonstrated the development
      of large atherosclerotic plaques in Helicobacter pylori-infected heterozygous
      LDLR+/- apoE+/- mice. OBJECTIVES: To measure novel biomarkers related to
      atherosclerosis, blood coagulation, and oxidative stress in order to investigate
      their possible pathogenic roles in atherosclerosis-prone mice. METHODS: Mice were
      fed with a normal chow diet or high-fat diet and sacrificed at different age
      intervals to measure aortic plaque size. Plasma cholesterol was enzymatically
      measured. Enzyme-linked immunosorbent assay was used to measure oxidized LDL
      (oxLDL)/beta-2-glycoprotein I (beta2GPI) complexes, immunoglobulin M (IgM)
      antibodies against native LDL, oxLDL, or oxLDL/beta2GPI, and urine 11-dehydro
      thromboxane B2 (11-dhTxB2) or 8-hydroxy-deoxyguanosine. RESULTS: There was a
      parallel increase in plaque size, plasma cholesterol, and urinary 11-dhTxB2 in
      atherosclerosis-prone mice. In contrast to atherosclerosis-prone strains, an
      elevation of urinary 11-dhTxB2 with no significant plaque generation was observed
      in LDLR+/- 1 apoE+/- mice. The atherogenic autoantigen oxLDL/beta2GPI complex was
      detected only in LDLRI mice. These levels seem to depend on plaque size. IgM
      antibodies against oxLDL in apoE-/- mice were found, accompanied by
      atherosclerotic progression. CONCLUSIONS: Progression of atherosclerotic lesions
      was associated not only with hypercholesterolemia but also with platelet
      activation and natural autoimmune-mediated regulatory mechanism(s) in murine
      models.

PMID- 21845969
TI  - Cystic tumors of the pancreas: high malignant potential.
AB  - BACKGROUND: Cystic tumors of the pancreas are rare, accounting for 10% of
      pancreatic cysts and 1% of all pancreatic tumors; surgery is dictated by their
      malignant potential. OBJECTIVES: To evaluate the malignancy rate of pancreatic
      cystic tumors and patient outcome, and to determine predictors for malignant
      potential. METHODS: We retrospectively reviewed the medical records of patients
      who underwent pancreatic resection for cystic tumors between January 1996 and
      December 2007. RESULTS: The charts showed that 116 patients were operated on for
      a pancreatic cystic tumor; most were women (63%). The chief complaint was
      abdominal pain (57%). Incidental detection occurred in 27%. Preoperative workup
      included ultrasound, tomography, endoscopic ultrasound and fine-needle aspiration
      biopsy. Indications for surgery were mucinous tumor, symptomatic or enlarging
      cyst under surveillance, high carcinoembryonic antigen levels within the cyst,
      and typical manifestations of intraductal papillary mucinous tumor (IPMT). All
      tumors but one were resectable. Whipple operation was performed in 40%, distal
      pancreatectomy in 55% and total pancreatectomy in 5%. Mucinous tumors were found
      in 40%, of which 37T were cystadenocarcinoma and/or borderline tumor. IPMT was
      found in 39%; 38% of them with cancer. Other pathologies included symptomatic
      serous cystadenomas, neuroendocrine cystic tumors and pseudopapillary tumors. The
      perioperative mortality rate was 2.6%. Five-year survival rates for patients with
      benign vs. invasive/borderline mucinous neoplasms was 90% vs. 59%, and for non
      invasive vs. invasive IPMT 89% vs. 45% respectively. CONCLUSIONS: Cystic tumors
      of the pancreas should be carefully evaluated. Surgery should be considered when
      a mucinous component is suspected due to the high rate of malignancy. Complete
      resection carries a high cure rate even in the presence of cancer.

PMID- 21845970
TI  - Efficacy of treatment for glioblastoma multiforme in elderly patients (65+): a
      retrospective analysis.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is an ultimately fatal disease that
      affects patients of all ages. Elderly patients (65 years and older) constitute a
      special subgroup of patients characterized by a worse prognosis and frequent
      comorbidities. OBJECTIVES: To assess the efficacy of different treatment
      modalities in terms of survival in elderly patients with GBM. METHODS: Using
      retrospective analysis, we extracted, anonymized and analyzed the files of 74
      deceased patients (aged 65 or older) treated for GBM in a single institution.
      RESULTS: Mean survival time was 8.97 months and median survival time 7.68 months.
      Patients who underwent tumor resection had a mean survival of 11.83 months, as
      compared to patients who underwent no surgical intervention or only biopsy and
      had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full
      radiation treatment had amean survival of 11.31 months, compared to patients who
      received only partial radiotherapy or none at all and had a mean survival of 4.09
      months (P < 0.0001). Patients who underwent chemotherapy had a mean survival of
      12.4 months, compared to patients who did not receive any chemotherapy andhad a
      mean survival of 5.89 months (P < 0.001). CONCLUSIONS: Age alone should not be a
      factor in the decision on which treatment should be given. Treatment should be
      individualized to match the patient's overall condition and his or her wishes,
      while taking into consideration the better overall prognosis expected with
      aggressive treatment.

PMID- 21845971
TI  - Functional outcome of elderly survivors of ischemic stroke: a retrospective study
      comparing nonhypercholesterolemic and hypercholesterolemic patients.
AB  - BACKGROUND: Total cholesterol is significantly associated with increased risk of
      ischemic stroke. Patients with ischemic stroke and high cholesterol levels may
      show better functional outcome after rehabilitation. OBJECTIVES: To study the
      possible interrelations between hypercholesterolemia and functional outcome in
      elderly survivors of ischemic stroke. METHODS: We conducted a retrospective chart
      review study of consecutive patients (age > or = 60 years) with acute stroke
      admitted to a geriatric rehabilitation ward in a university-affiliated hospital.
      The presence or absence of hypercholesterolemia was based on registry data
      positive for hypercholesterolemia, defined as total cholesterol > or = 200 mg/dl
      (5.17 mmol/L). Functional outcome of patients with hypercholesterolemia (Hchol)
      and without (NHchol) was assessed by the Functional Independence Measurement
      scale (FIM) at admission and discharge. Data were analyzed by t-test and chi
      square test, as well as linear regression analysis. RESULTS: The complete data
      for 551 patients (age range 60-96 years) were available for final analysis; 26.7%
      were diagnosed as having hypercholesterolemia. Admission total FIM scores were
      significantly higher in patients with Hchol (72.1 +/- 24.8) compared with NHchol
      patients (62.2 +/- 24.7) (P < 0.001). A similar difference was found at discharge
      (Hchol 90.8 +/- 27.9 vs. NHchol 79.7 +/- 29.2, P < 0.001). However, total FIM
      change upon discharge was similar in both groups (18.7 +/- 13.7 vs. 17.6 +/-
      13.7, P = 0.4). Regression analyses showed that high Mini Mental State
      Examination scores (beta = 0.13, P = 0.01) and younger age (beta = -0.12, P =
      0.02) were associated with higher total FIM change scores upon discharge. Total
      cholesterol was not associated with better total FIM change on discharge (beta = 
      0.012, P = 0.82). CONCLUSIONS: Elderly survivors of stroke with Hchol who were
      admitted for rehabilitation showed higher admission and discharge FIM scores but
      similar functional FIM gains as compared to NHchol patients. High cholesterol
      levels may be useful in identifying older individuals with a better
      rehabilitation potential.

PMID- 21845972
TI  - Current changes in the management and outcome of patients with curable colorectal
      cancer.
AB  - BACKGROUND: Major changes in the evaluation and treatment of curable colorectal
      cancer (CRC) have emerged in the last two decades. These changes have led to
      better patient outcome overtime. OBJECTIVES: To evaluate the impact of these
      changes as reflected in the difference in long-term outcome of a consecutive
      group of recently laparoscopically operated curable CRC patients and a
      consecutive group of patients operated 20 years earlier in the same department.
      METHODS: Data of the new group were taken from our prospectively collected data
      of patients who underwent elective laparoscopic surgery for CRC in recent years.
      Data regarding patients operated on 20 years ago were retrieved from previous
      prospectively collected data on the long-term survival of CRC patients operated
      in the same department. RESULTS: The recently operated group comprised 203
      patients and the previous group 199 patients. Perioperative mortality was 0.5% in
      the new group versus 1.5% in the old group (not significant). There were more
      early-stage and more proximal tumors in the recently operated group. A Kaplan
      Meier 5-year survival analysis revealed no difference between stage I patients of
      the two groups. However, there was a significant increase in 5-year survival in
      the new group for stage II (85% vs. 63%, P = 0.004) and for stage III patients
      (57% vs. 39%, P = 0.01). This trend was maintained after removing the rectal
      cancer patients from the calculated data. CONCLUSIONS: We have demonstrated
      improved survival for stage II and ILL CRC patients overa 20-year period in the
      same medical center. This change most likely reflects advances both in imaging
      techniques leading to more accurate staging and in adjuvant treatments.

PMID- 21845973
TI  - Pheochromocytoma: progress and challenges.

PMID- 21845974
TI  - Cardiopulmonary resuscitation in the pregnant patient--an update.

PMID- 21845975
TI  - Malignant pheochromocytoma of the urinary bladder: challenges in diagnosis and
      management.

PMID- 21845976
TI  - Basilar artery occlusion presenting as a tonic-clonic seizure.

PMID- 21845977
TI  - Healing of refractory leg ulcer in a patient with thalassemia intermedia and
      hypercoagulability after 14 years of unresponsive therapy.

PMID- 21845978
TI  - Melanosis enteri discovered on capsule endoscopy of the small bowel.

PMID- 21845979
TI  - Metastatic breast cancer imitating acute diverticulitis.

PMID- 21845980
TI  - Mind the gap: policy and practice in the reform of healthcare.

PMID- 21845981
TI  - The role of individual diligence in improving safety.
AB  - PURPOSE: This paper aims to be a theoretical examination of the role of
      individuals in sponsoring and facilitating effective, systemic change in
      organisations. Using reports of a number of high-profile initiatives to improve
      patient safety, it seeks to analyse the role of individual health care
      professionals in developing and facilitating new systems of care that improve
      safety and quality. DESIGN/METHODOLOGY/APPROACH: The paper uses recent work in
      sociology that is concerned with the phenomenon of "sociological citizenship".
      The authors test whether successful initiators of change in health care can be
      described as sociological citizens. This notion of sociological citizens is
      applied to a number of highly successful initiatives to improve safety and
      quality to extrapolate the factors associated with individual clinician
      leadership, which may have affected the success of such endeavours. FINDINGS: In
      each of the examples analysed the initiators of change can be characterised as
      sociological citizens. In reviewing the roles of these charismatic individuals it
      is evident that they see the relational interdependence between the individuals
      and organisations and that they use this information to achieve both professional
      and organisational objectives. RESEARCH LIMITATIONS/IMPLICATIONS: The paper uses
      a case study method to investigate the usefulness of the role of sociological
      citizenship in interventions that aim to improve patient safety. The paper
      reviews the key concepts and uses of the concept of sociological citizenship to
      produce a framework against which the case studies were assessed. PRACTICAL
      IMPLICATIONS: The authors suggest that a goal of policy for improving patient
      safety should be directed to the problem of how hospitals and health care
      organisations can create the conditions for encouraging the individual diligence
      and care that is needed to support reliable, safe health care practices. SOCIAL
      IMPLICATIONS: Improving the safety and quality of health care is an important
      public health initiative. It has also proven to be difficult to achieve sustained
      reductions in the harm caused by the occurrence of adverse events in health care.
      The process of linking individual diligence with service outcomes may help to
      overcome one of the enduring struggles of health care systems around the world:
      the policy-practice divide. ORIGINALITY/VALUE: The paper directs attention
      towards the role of sociological citizenship in health care systems and
      organisations.

PMID- 21845982
TI  - Introducing innovation in a management development programme for a UK primary
      care organisation.
AB  - PURPOSE: The aim of this paper is to examine the introduction of innovation as
      part of a management development programme at a primary care organisation, a
      legal form known as a Primary Care Trust (PCT), in the UK.
      DESIGN/METHODOLOGY/APPROACH: The paper draws on experience of managing a
      successful management development programme for a PCT. The report of the case
      study analyses the key events that took place between 2008 and 2010, from direct
      observation, surveys, discussion and documentary evidence. FINDINGS: The Northern
      PCT has partnerships with a number of educational providers to deliver their
      leadership and management development programmes. A close working relationship
      had developed and the programme is bespoke - hence it is current and of practical
      use to the UK's National Health Service (NHS). In addition, there are regular
      meetings, with module leaders gaining a firsthand understanding of the
      organisation's needs and aspirations. This has resulted in a very focused and
      personalised offering and a genuine involvement in the programme and individuals
      concerned. RESEARCH LIMITATIONS/IMPLICATIONS: The research was conducted among a
      relatively small sample, and there is a lack of previous literature evidence to
      make significant comparisons. PRACTICAL IMPLICATIONS: The paper identifies key
      implications for practitioners and educators in this area. ORIGINALITY/VALUE:
      This paper is one of few to investigate innovation and improvement in the NHS,
      and is unique in that it uses the lenses of a management development programme to
      explore this important, and under-researched, topic.

PMID- 21845983
TI  - High performance work systems: the gap between policy and practice in health care
      reform.
AB  - PURPOSE: Studies of high-performing organisations have consistently reported a
      positive relationship between high performance work systems (HPWS) and
      performance outcomes. Although many of these studies have been conducted in
      manufacturing, similar findings of a positive correlation between aspects of HPWS
      and improved care delivery and patient outcomes have been reported in
      international health care studies. The purpose of this paper is to bring together
      the results from a series of studies conducted within Australian health care
      organisations. First, the authors seek to demonstrate the link found between high
      performance work systems and organisational performance, including the perceived
      quality of patient care. Second, the paper aims to show that the hospitals
      studied do not have the necessary aspects of HPWS in place and that there has
      been little consideration of HPWS in health system reform.
      DESIGN/METHODOLOGY/APPROACH: The paper draws on a series of correlation studies
      using survey data from hospitals in Australia, supplemented by qualitative data
      collection and analysis. To demonstrate the link between HPWS and perceived
      quality of care delivery the authors conducted regression analysis with tests of
      mediation and moderation to analyse survey responses of 201 nurses in a large
      regional Australian health service and explored HRM and HPWS in detail in three
      casestudy organisations. To achieve the second aim, the authors surveyed human
      resource and other senior managers in all Victorian health sector organisations
      and reviewed policy documents related to health system reform planned for
      Australia. FINDINGS: The findings suggest that there is a relationship between
      HPWS and the perceived quality of care that is mediated by human resource
      management (HRM) outcomes, such as psychological empowerment. It is also found
      that health care organisations in Australia generally do not have the necessary
      aspects of HPWS in place, creating a policy and practice gap. Although the chief
      executive officers of health service organisations reported high levels of
      strategic HRM, the human resource and other managers reported a distinct lack of
      HPWS from their perspectives. The authors discuss why health care organisations
      may have difficulty in achieving HPWS. ORIGINALITY/VALUE: Leaders in health care
      organisations should focus on ensuring human resource management systems,
      structures and processes that support HPWS. Policy makers need to consider HPWS
      as a necessary component of health system reform. There is a strong need to
      reorient organisational human resource management policies and procedures in
      public health care organisations towards high performing work systems.

PMID- 21845984
TI  - Mind the gap: Understanding utilisation of evidence and policy in health care
      management practice.
AB  - PURPOSE: The paper aims to take a reflective stance on the relationship between
      policy/evidence and practice, which, the authors argue, is conceptually under
      developed. The paper aims to show that current research perspectives fail to
      frame evidence and policy in relation to practice. DESIGN/METHODOLOGY/APPROACH: A
      qualitative study was conducted in the English NHS in four Primary Care Trusts
      (PCTs). Seventy-five observations of meetings and 52 semi-structured interviews
      were completed. The approach to data analysis was to explore and reconstruct
      narratives of PCT managers' real practices. FINDINGS: The exploratory findings
      are presented through two kinds of narratives. The first narrative vividly
      illustrates the significance of the active involvement, skills and creativity of
      health care practitioners for policy implementation. The second narrative
      elucidates how problems of collaboration among different experts in PCTs might
      emerge and affect evidence utilisation in practice. PRACTICAL IMPLICATIONS: The
      findings exemplify that policies are made workable in practice and, hence, policy
      makers may also need to be mindful of practical intricacies and conceive policy
      implementation as an iterative process. ORIGINALITY/VALUE: The contribution of
      this paper lies in offering an alternative and important perspective to the
      debate of utilisation of policy/evidence in health care management and in
      advancing existing understanding of health care management practice. The paper's
      rich empirical examples demonstrate some important dimensions of the complexity
      of practice.

PMID- 21845985
TI  - Inconsistency in health care professional work: Employment in independent sector
      treatment centres.
AB  - PURPOSE: The purpose of this paper is to investigate the impact of recent
      outsourcing and public-private partnership (PPPs) arrangements on the consistency
      of professional employment in health care. DESIGN/METHODOLOGY/APPROACH: A case
      study methodology is applied. FINDINGS: The paper finds that multiple
      arrangements for employment within the ISTC creates numerous sources for
      inconsistency in employment: across the workplace, within professional groups and
      with national frameworks for health care employment. These are identified as
      having implications for organisational outcomes, threatening the stability of
      current partnerships, and partially stymieing intended behavioural change.
      RESEARCH LIMITATIONS/IMPLICATIONS: The study is a single case study of an
      independent sector treatment centre. Future research is required to investigate
      wider trends of employment in heterogeneous outsourcing and PPP arrangements.
      PRACTICAL IMPLICATIONS: The paper informs both managers and clinical
      professionals of the unanticipated complexities and practical challenges that can
      arise in partnerships and outsourcing arrangements. ORIGINALITY/VALUE: The paper
      presents a unique in-depth investigation of employment within recently
      established ISTCs, and highlights important employment changes for the core
      health care workforce and high-status professionals in the evolving health care
      organisational landscape.

PMID- 21845986
TI  - Barriers in implementation of evidence-based practice: Supported employment in
      Swedish context.
AB  - PURPOSE: The aim of this paper is to identify initial barriers influencing
      implementation of supported employment (SE). SE, according to the individual
      placement and support (IPS) approach, has been recognised as an evidence-based
      method to help people with severe mental illness to find regular employment.
      DESIGN/METHODOLOGY/APPROACH: A systematic implementation evaluation of the first
      randomised controlled SE (IPS) trial in Sweden was conducted in August 2008 and
      August 2009. Data were collected on a regular basis from SE employment
      specialists, process heads, clients and representatives from mental health care
      units and vocational services (social insurance and public employment offices)
      using interviews, non-participant observations and document analysis. FINDINGS:
      SE employment specialists reported that existing regulations for social insurance
      and employment regulations presented major obstacles to implementation.
      Difficulties were reported in cooperation with handling officers at the
      vocational services. Scepticism towards persons with mental illness was common
      and employers expected to receive subsidies if they hired a person with mental
      illness. SE participants expressed fear of losing their social benefits.
      ORIGINALITY/VALUE: The results illuminate a collision between an innovative
      evidence-based practice and the existing systems for social benefits and work
      rehabilitation.

PMID- 21845987
TI  - Financing public healthcare institutions in Ghana.
AB  - PURPOSE: The financing of healthcare services has been of a major concern to all
      governments in the face of increasing healthcare costs. For developing countries,
      where good health is considered a poverty reduction strategy, it is imperative
      that the hospitals used in the delivery of healthcare services are well financed
      to accomplish their tasks. The purpose of this paper is to examine how public
      hospitals in Ghana are financed, and the challenges facing the financing modes
      adopted. DESIGN/METHODOLOGY/APPROACH: To achieve the objectives of the study, one
      major public healthcare institution in Ghana became the main focus. FINDINGS: The
      findings of the study revealed that the main sources of financing the public
      healthcare institution are government subvention, internally-generated funds and
      donor-pooled funds. Of these sources, the internally generated fund was regarded
      as the most reliable, and the least reliable was the donor-pooled funds. Several
      challenges associated with the various financing sources were identified. These
      include delay in receipt of government subvention, delay in the reimbursement of
      services provided to subscribers of health insurance schemes, influence of
      government in setting user fees, and the specifications to which donor funds are
      put. ORIGINALITY/VALUE: The findings of this study have important implications
      for improving the financing of public healthcare institutions in Ghana. A number
      of recommendations are provided in this regard.

PMID- 21845988
TI  - Operational and contextual drivers of hospital costs.
AB  - PURPOSE: The purpose of this paper is to examine empirically how operational
      performance and contextual factors contribute to differences in overall patient
      care costs across different hospitals. DESIGN/METHODOLOGY/APPROACH:
      Administrative data are employed from a sample of hospitals in New York State to
      construct measures of contextual factors, operational performance, and cost per
      patient. Operational performance and cost variables are adjusted to account for
      case mix differences across hospitals. Hierarchical regression is used to analyze
      the effects of contextual and operational variables on cost performance.
      FINDINGS: Increased length of stay, increased patient volume, and educational
      mission were associated with higher cost per patient. Mortality performance was
      associated with lower cost per patient. However, it was not found that location,
      size, or ownership status had a significant relationship with cost performance.
      PRACTICAL IMPLICATIONS: This paper identifies several significant relationships
      between contextual and operational variables and hospital costs. From a
      managerial perspective, these findings highlight the fact that some drivers of
      cost in hospitals are under the control of managers. One of the primary cost
      drivers in the study is length of stay, which implies that there is significant
      room for improvement in healthcare performance through a focus on operational
      excellence. ORIGINALITY/VALUE: For researchers, the present study highlights the
      relative importance of operational versus contextual factors, with respect to
      cost performance in hospitals. The results of this study also provide direction
      for additional research into the role operational performance might play in
      determining the overall organizational performance in a hospital.

PMID- 21845989
TI  - Women leaders: the social world of health care.
AB  - PURPOSE: The purpose of this paper is to illustrate a microcosm of the
      complexities that women face in a masculine environment.
      DESIGN/METHODOLOGY/APPROACH: Ten women administrators were selected from one
      Southeastern University in the USA, using criterion sampling. The interviews of
      five women from male-dominated colleges (greater than 50 percent male faculty-MD)
      and five from female-dominated fields (FD) were analyzed. For further study, the
      texts of the four women from healthcare colleges were compared with the six from
      non-healthcare fields. Interviewees were asked questions about their background,
      leadership and power. Confidentiality was adhered to according to the
      university's IRB guidelines and policies. FINDINGS: The social world of the
      healthcare Deans was evident and was shaped around a "rigid hierarchy of
      authority and power" that goes beyond gender and is stratified among health
      related professions. ORIGINALITY/VALUE: This examination of the hierarchical
      discourse of power within the social world of healthcare gives valuable
      instruction for women's negotiation through adaptation.

PMID- 21845990
TI  - CEO perceptions of organizational consensus and its impact on hospital
      restructuring outcomes.
AB  - PURPOSE: Increased competition and resource scarcity have caused hospitals to
      seek internal efficiencies by restructuring their structures and processes. The
      purpose of this paper is to examine the effects of an organization's orientation
      toward control and learning and the use of process facilitators on perceived
      organizational consensus on outcomes related to cost, quality, and the ability to
      sustain implemented changes following a major hospital restructuring.
      DESIGN/METHODOLOGY/APPROACH: Data from 263 hospitals from across the USA were
      collected. Factor analysis was employed to develop scales measuring the
      organization's emphasis on learning, controls, and processes. Regression analysis
      then examined their relationship to the consensus on restructured outcomes.
      FINDINGS: The findings suggest a positive relationship between a learning
      orientation and processes with improved perceived agreement on restructuring
      outcomes. Hospitals with control orientations have a negative relationship with
      perceived organizational consensus. RESEARCH LIMITATIONS/IMPLICATIONS: The
      research has some limitations. The primary data for both the CEOs' and employees'
      perspectives comes from hospital CEOs. Also, the study is a cross-sectional study
      and lacks longitudinal information. It also includes mostly not-for-profit
      hospitals, with 100 or more beds, in urban areas. Practical implications -
      Hospitals will continue to feel pressures for the need to restructure and change.
      The findings suggest that hospitals achieve better results if they foster a
      learning orientation and put in place processes to facilitate the challenges of
      change. Although control systems are important, executives should realize that
      they might impede organizational efforts during organizational change. Hospitals
      may succeed in their change efforts by balancing adequate control and learning
      that are supported by processes to facilitate restructuring efforts.
      ORIGINALITY/VALUE: The work provides an original study on the effects of an
      organization's orientation of learning and controls and change processes on the
      perceived consensus of restructuring outcomes. The dichotomy of learning and
      controls has not been applied to hospital consensus on outcomes. The research
      suggests that hospitals can improve their change efforts by implementing
      appropriate processes and greater learning mechanisms. During times of stress and
      change hospitals often become more control oriented, which may create greater
      misalignments and ineffective change. Managers should learn from the research
      that appropriate processes and learning will provide better consensus and more
      effective change.

PMID- 21845991
TI  - Efficiency and productivity of hospitals in Vietnam.
AB  - PURPOSE: The purpose of this paper is to examine the relative efficiency and
      productivity of hospitals during the health reform process.
      DESIGN/METHODOLOGY/APPROACH: Data envelopment analyses method (DEA) with the
      input-oriented variable-returns-to-scale model was used to calculate efficiency
      scores. Malmquist total factor productivity index approach was then employed to
      calculate productivity of hospitals. Data of 101 hospitals was extracted from
      databases of the Ministry of Health, Vietnam from the years 1998 to 2006.
      FINDINGS: There was evidence of improvement in overall technical efficiency from
      65 per cent in 1998 to 76 per cent in 2006. Hospitals' productivity progressed
      around 1.4 per cent per year, which was mainly due to the technical efficiency
      improvement. Furthermore, provincial hospitals were more technically efficient
      than their central counterparts and hospitals located in different regions
      performed differently. ORIGINALITY/VALUE: The paper provides an insight in the
      performance of Vietnamese public hospitals that has been rarely examined before
      and contributes to the existing literature of hospital performance in developing
      countries

PMID- 21845992
TI  - Assessing hospitals' readiness for clinical governance quality initiatives
      through organizational climate.
AB  - PURPOSE: The purpose of this paper is to consider organisational climate as the
      vehicle to get an understanding, map and enhance the appropriate organisational
      culture for good clinical governance (CG). Based on this assertion, the purpose
      of this research is fourfold: to investigate CG attributes embedded in Greek
      hospitals' climate; to test the validity and reliability of the Clinical
      Governance Climate Questionnaire (CGCQ) and highlight the dimensions of CG
      climate in the Greek context; to illuminate the "red flag" aspects of hospital's
      climate and areas shaping the perceptions of the quality of the provided
      services; and to explore the influence of hospital's legal status on CG climate
      and service quality. DESIGN/METHODOLOGY/APPROACH: Empirical research using the
      CGCQ was conducted in three Greek NHS hospitals. A total of 214 usable
      questionnaires completed by the hospitals' personnel were gathered. FINDINGS: The
      validity and reliability tests proved that the study's five-dimension structure
      of CGCQ is capable of conceptualising the basic elements of CG climate in the
      Greek context. Hospital's climate was found to be not supportive to successful CG
      implementation, and areas that demand attention were illuminated. Hospital's
      legal status seems to mediate CG climate and service quality. PRACTICAL
      IMPLICATIONS: CGCQ proved to be a useful tool for managers and policymakers to
      trace "problematic" areas of hospital's climate and develop strategies for
      successful CG initiatives. ORIGINALITY/VALUE: The paper contributes to the field
      of health care management, since it demonstrates that CG climate can be used as a
      "gauge" of the prevailing CG culture. CGCQ is revealed as a valid, reliable and
      flexible tool.

PMID- 21845993
TI  - Venous thromboembolism in shoulder surgery: a systematic review.
AB  - Although it is generally believed that venous thromboembolism (VTE) after
      shoulder surgery is very rare, there are increasing reports of deep venous
      thrombosis (DVT) and pulmonary embolism (PE) associated with shoulder surgery. To
      our knowledge only few studies have reviewed the available evidence on the
      subject. The purpose of this study was to review the available evidence in the
      published literature regarding incidence, risk factors, diagnosis and management
      of DVT/PE following shoulder surgery (Level IV evidence).

PMID- 21845994
TI  - The volar portal in wrist arthroscopy.
AB  - Wrist arthroscopy is not only a diagnostic tool; it has also developed into a
      valuable treatment alternative for several wrist disorders. All of the standard
      portals are dorsally located, leaving the dorsal sector of the radiocarpal and
      midcarpal joint partially invisible. A volar portal has been developed through
      the bed of the flexor carpi radialis tendon, thus expanding the therapeutic
      possibilities. We report our personal experience with the use of a volar portal
      in 28 of 206 (14%) wrist arthroscopies. No technical problems or neurovascular
      complications were encountered. We think the standardized approach as described
      is valuable and safe.

PMID- 21845995
TI  - Primary subacute osteomyelitis of the talus in children: a case series and
      review.
AB  - Subacute haematogenous osteomyelitis of the talus in children is a rare
      condition. All previously reported cases have been managed by hospital admission
      with surgical debridement and antibiotics or by intravenous antibiotic therapy
      followed by oral antibiotics. This case series documents the management of the
      condition at our institution and reviews the current published literature. We
      conclude that with appropriate patient selection, primary subacute haematogenous
      osteomyelitis of the paediatric talus can be managed on an out-patient basis with
      oral antibiotic therapy.

PMID- 21845996
TI  - Open reduction and internal fixation of humeral non-unions: radiological and
      functional results.
AB  - This study aimed at assessing the effectiveness of open reduction and plate
      fixation combined with autogenous bone grafting in the treatment of non-united
      fractures of the humeral shaft. Forty six patients (27 men, 19 women; mean age,
      35.6 years; range, 23-53 years) were operated on for non-union of a diaphyseal
      fracture of the humerus. Sixteen patients had surgical treatments and 30 patients
      had non-surgical treatments prior to operation. They were operated on average 7.8
      months (6-17) following their initial treatment. None of the nonunions were
      infected. Radial nerve deficit was present in no patient. Treatment included open
      reduction and plate fixation combined with autogenous bone grafting. The mean
      follow-up period was 26 months (range: 13-41). No patient was lost to follow-up.
      The operative time averaged 91 minutes (range: 68-123). Union was achieved in all
      patients in a mean of 6.1 months (range: 5-13). There were nine postoperative
      complications (superficial infection in 5 and radial nerve palsy in 4). The
      infections resolved after local treatment. The radial nerve palsies recovered
      spontaneously. On clinical evaluation, shoulder range of motion was excellent in
      41 patients (89.1%), and moderate in five patients (10.9%). Elbow range of motion
      was excellent in 30 patients (65.2%), moderate in 14 patients (30.4%) and poor in
      2 patients (4.4%). Functional results were excellent in 24 patients (522%), good
      in 14 patients (30.4%), fair in 6 patients and poor in 2 patients (04.4%). In
      this study, plate fixation combined with autogenous bone grafting appeared as a
      safe and effective option in non-infected non-union of the humeral shaft.

PMID- 21845997
TI  - Linked total elbow arthroplasty as treatment of distal humerus nonunions in
      patients older than 70 years.
AB  - Treatment of distal humerus nonunions may be challenging, especially in the
      elderly patient. Total elbow replacement has been proposed as an option in
      selected patients, but a high index of complications has been reported. We
      present the results of a linked elbow replacement in six patients older than 70
      years with a symptomatic nonunion of the distal humerus. At a mean follow-up of
      40 months, average range of motion was from 15 degrees to 125 degrees of flexion
      extension. Only one patient had moderate pain in the elbow, but all six were
      satisfied with the results of the operation. The arthroplasty allowed all
      patients to do basic tasks of daily living activities. Our results are
      encouraging, and show that linked elbow replacement is a good option in elderly
      patients with symptomatic nonunions of the distal humerus. Appropriate selection
      of ideal candidates for this procedure is a key factor in reducing the risk of
      complications.

PMID- 21845998
TI  - Provider volume and short term complications after elective total hip
      replacement: an analysis of Belgian administrative data.
AB  - The relationship between provider volume and short term complications after an
      elective total hip replacement was studied on Belgian hospital discharge
      administrative database from 2004. The analysis included 11 856 patients.
      Hospitals were classified in low-volume (< or = 60/interventions per year),
      medium volume (61-110) or high volume (>110). Surgeons were labelled low-volume
      (< or = 6), medium volume (7-20) or high volume (>20). After adjustment for age,
      sex, principal diagnosis and comorbidity, surgeon volume was much more predictive
      of short term complications than centre volume. Patients treated by small volume
      surgeons (respectively medium volume surgeons) had a 43% higher odds of
      complications than patients operated by high volume surgeons (respectively 37%).
      Despite some limitations, Belgian administrative hospital discharge databases can
      be used to assess the volume outcome relationship for orthopaedic surgery. The
      study has emphasized the need to closely monitor individual performance, for
      hospitals and surgeons. Providers requiring further auditing can be effectively
      identified with funnel plots used routinely in quality control programs.

PMID- 21845999
TI  - Initial stability of tibial components in primary knee arthroplasty. A cadaver
      study comparing cemented and cementless fixation techniques.
AB  - The purpose of this roentgen stereophotogrammetric analysis (RSA) study was to
      evaluate the initial stability of cemented and cementless tibial components in
      vitro. Twenty tibia specimens were matched into two groups. In the first group,
      the tibial trays were cemented superficially and in the second group cementless
      fixation with stem and screws was performed. An axial load of 2000 N for 1000 and
      10,000 cycles was applied onto the specimens and RSA was performed. The
      experimental results after 1000 cycles showed a higher migration with significant
      differences for the parameters maximum lift off (p = 0.011) and maximum total
      point motion (p = 0.002) in the cementless group. After 10,000 cycles, the
      migration in the cementless group increased significantly for maximum lift off (p
      = 0.043), maximum subsidence (p = 0.045) and maximum total point motion (p =
      0.013). The higher migration rates in the cementless group demonstrate a lower
      initial mechanical stability of cementless tibial components which can cause an
      early component loosening.

PMID- 21846000
TI  - Reliability of the hip-to-ankle radiograph in determining the knee and implant
      alignment after total knee arthroplasty.
AB  - Hip-to-ankle radiographs have been used to evaluate lower limb alignment before
      and after total knee arthroplasty. However, earlier studies have inappropriately
      used correlation to assess the reproducibility of the radiographs. We determined
      the reliability of the hip-to-ankle radiograph using the Bland-Altman analysis.
      Two consecutive hip-to-ankle radiographs were obtained in 52 patients (52 knees)
      after total knee arthroplasty. There was an excellent agreement between
      mechanical axis angles, tibiofemoral angles, and femoral and tibial component
      alignment in the two radiographs. There was also an excellent agreement between
      all intra and interobserver analyses. The hip-to-ankle radiograph appears to be a
      reliable and reproducible means for determining the alignment of the knee in the
      coronal plane after total knee arthroplasty. In routine follow-up, the short
      anteroposterior knee radiograph may provide sufficient information. However, only
      the hip-to-ankle radiograph provides accurate information on the weightbearing
      mechanical axis in patients with suspected lower limb malalignment.

PMID- 21846001
TI  - Knee arthroscopy and driving. Results of a prospective questionnaire survey and
      review of the literature.
AB  - Orthopaedic surgeons routinely advise patients when to drive after surgical
      procedures. There are however very few guidelines concerning the return to
      driving after an orthopaedic operation. We performed a literature search and
      found very limited studies or research regarding this topic and in particular
      following arthroscopic surgery. We subsequently conducted a prospective
      questionnaire survey from one hundred knee arthroscopy patients attending
      outpatient follow-up clinics. Results showed the advice given to patients was
      delivered by doctors of differing levels of experience, but interestingly the
      majority of patients did not know the grade of doctor they were being consented
      by. Our study has highlighted that the advice given to patients was inconsistent.
      Patients returned to driving over a variety of time frames from one day to
      greater than three weeks. No adverse events were reported but 14% chose not to
      answer this question. We have illustrated the need for thorough consenting,
      further research in this area, and the development of universal guidelines
      surrounding the return to driving after surgery.

PMID- 21846002
TI  - Factors affecting isokinetic muscle strength before and after anterior cruciate
      ligament reconstruction.
AB  - The purpose of this study was to evaluate the factors affecting muscle strength
      of ACL-deficient knees before and after ACL reconstruction. The study included
      122 male patients who underwent primary ACL reconstruction with a bone-patellar
      tendon-bone autograft. Preoperative loss and change in muscle strength in both
      extensor and flexor muscle groups after ACL reconstruction were calculated
      separately at 60 degrees/sec and 180 degrees/sec angular velocities. We evaluated
      the effect of surgical delay on the preoperative deficit and on its change after
      surgery. Muscle strength change after ACL reconstruction was also evaluated in
      relation to patient compliance to treatment. The longer the delay of ACL
      reconstruction the more the muscle strength deficit of flexor and extensor
      muscles increased. In the ACL deficient knees with high strength deficit,
      improvement in muscle strength was higher after ACL reconstruction for both
      muscle groups. When delay of ACL reconstruction was short and the patient was
      compliant to treatment, flexor muscle strength recovery was early. Shortening the
      delay to reconstruction had a positive influence on muscle strength after ACL
      reconstruction when preoperative muscle strength deficit was high.

PMID- 21846003
TI  - Indirect reduction and hybrid external fixation in management of comminuted
      tibial plateau fractures.
AB  - The aim of the present study is to assess the results of indirect reduction and
      hybrid external fixation in management of comminuted tibial plateau fractures.
      The study included 28 patients with high-energy tibial plateau fractures
      (Schatzker type V and VI). The ages ranged from 22 to 58 years with an average of
      35 years. The trauma was a road traffic accident in 16 cases and a fall from a
      height in 12 cases. Concomitant soft tissue injuries were present in 18 cases
      such as skin wounds in 6 cases, excessive swelling with skin blisters in 9 cases,
      and compartment syndrome in 3 cases. After clinical and radiological evaluation
      all the patients were treated by indirect reduction using a traction table and a
      hybrid external fixator. The average time to healing was 3.2 months. At the final
      follow-up the range of knee movement ranged from 0 degrees-140 degrees with an
      average of 110 degrees. The results were satisfactory in 23 cases and
      unsatisfactory in 5 cases according to the Rasmussen knee functional score.
      Complications included pin tract infection in 12 cases, an extension lag in 2
      cases, varus deformity of about 15 degrees in one case, deep infection in one
      case and early osteoarthritic changes in 2 cases. Hybrid external fixation is a
      good method for treatment of comminuted tibial plateau fractures. It allows for
      early joint movement and reduces the risk of serious complications.

PMID- 21846004
TI  - The anterolateral incision for pilon fracture surgery: an anatomic study of
      cutaneous blood supply.
AB  - The purpose of this study was to examine the blood supply to the adjacent skin
      and its vulnerability to anterolateral tibial plating performed with fibular
      plating through a single surgical incision. Ten lightly embalmed cadaver legs
      without a history of lower extremity trauma or surgery with a mean age of 71
      years (range, 57 to 87 years) were used for this investigation. Each specimen was
      injected with a commercially available silicone compound through the popliteal
      artery. The left leg was plated through a modified extensile Bohler approach and
      the right leg served as the control. Each leg was anatomically dissected. All
      measurements were taken using a digital caliper by a single investigator. A mean
      of 93 (range, 4 to 17) perforating arteries were present and in the proximity of
      the fibula plate. Our findings suggest the potential for iatrogenic soft tissue
      breakdown along the posterior border of the anterolateral surgical incision in
      this procedure as a result of compromised blood supply to the skin.

PMID- 21846005
TI  - The outcome of locking plate fixation for the treatment of periarticular
      metastases.
AB  - Periarticular bone metastasis may be treated with endoprosthetic reconstruction.
      The extensive surgery required may not, however, be appropriate for all patients.
      Our aim was to establish whether locking plates provide good functional outcomes
      and a durable construct when used in the management of metastatic disease.
      Prospective data collection was performed. Twenty one patients underwent surgery
      for periarticular metastatic tumours. The median duration of followup for
      surviving patients is one year. There have been no cases of implant failure and
      no requirement for revision surgery. Pain relief was excellent or good in the
      majority of patients. Patients who had sustained a fracture prior to fixation had
      restoration of their WHO performance status. All patients had a dramatic
      improvement in their MSTS scores. The median pre-operative score was 15% (0%-37%)
      improving to a median score of 80% (75%-96%) post operatively. Locking plates
      were found to provide reliable fixation and excellent functional restoration in
      selected patients suffering from periarticular metastatic bone disease.

PMID- 21846006
TI  - Balloon kyphoplasty: scintigraphy as the ultimate decision maker?
AB  - Balloon kyphoplasty is still controversial as a treatment for vertebral
      compression fractures (VCFs) due to osteoporosis. Nevertheless, the authors
      conducted a prospective study in 60 patients about the effectiveness of
      scintigraphy, after the conventional roentgenographic examination, as an ultimate
      decision maker for the identification of the levels to be treated. Seventy-one
      levels were radiographically and scintigraphically positive, were seen as active,
      and thus treated. Thirty-seven levels were radiographically negative but positive
      scintigraphically, were considered as imminent fractures, and thus treated. Ten
      levels were positive radiographically, but negative scintigraphically, and were
      not treated as they were considered as healed. The Oswestry Disability Score
      (100% = worst possible condition) improved from 38.8% +/- 39.5% at baseline, to
      2.38% +/- 3.99% on the first postoperative day (p < 0.001), to 2.00% +/- 3.40% at
      1 month (p < 0.001) and to 1.93% +/- 3.33% at 6 months (p < 0.001). This
      preliminary study gives a hint that scintigraphy might work as the ultimate
      decision maker, even when plain radiographs are negative. Further studies will be
      needed to compare patients with VCFs positive radiographically and
      scintigraphically, and other patients with VCFs negative radiographically, but
      positive scintigraphically.

PMID- 21846007
TI  - A quantitative assessment of facial protection systems in elective hip
      arthroplasty.
AB  - We aimed to assess the risk to surgeons of blood splatter during total hip
      arthroplasty. Hoods from personal protection systems used in 34 consecutive total
      hip replacements were collected and the area of blood splatter was measured and
      compared to goggles and visors. Thirty one primary THA's (13 cemented, 4 hybrid,
      14 uncemented) and 3 revisions (1 hybrid, 2 uncemented) were collected. Splashes
      were detected on all of the masks with a mean of 034% cover. Splatter was
      greatest for the operating surgeon, followed by the first assistant, though the
      difference was not statistically significant. Operating personnel were at greater
      risk of contamination during uncemented arthroplasty (p < 0.0001; 95% CI). On
      average 50.60% and 45.40% of blood cover was outside the area protected by
      goggles and visors respectively. There was a significant difference between the
      Personal Protection Systems (PPS) and goggles (p = 0.0231; 95% CI) as well as
      between the PPS and visors (p = 0.0293; 95% CI).

PMID- 21846008
TI  - Screening femoral heads from living donors: a prospective study comparing swab
      agar versus bone fragment-broth culture.
AB  - Femoral heads are an important source of allograft bone used in reconstructive
      orthopaedic surgery. The sterility of donor material is of major importance for
      the recipient. Femoral heads intraoperatively retrieved during hip arthroplasty
      from medically screened living donors are routinely checked with a surface swab
      to exclude microbiological contamination. There is, however, evidence that swab
      cultures have limited sensitivity. We therefore prospectively compared two ways
      of screening femoral heads. Bacterial recovery from swabs in Amies transport
      medium taken intraoperatively, subsequently transported to the microbiology
      laboratory and inoculated on agar and in broth was compared with the recovery
      from a bone fragment also taken intraoperatively but immediately inoculated into
      Wilkins Chalgren broth. Forty femoral heads were tested with both methods.
      Bacteria were cultured neither from the femoral surface swabs nor from the
      femoral fragments. Consequently no distinct conclusions regarding the sensitivity
      of both techniques could be drawn. In addition the bacterial yield of two swabs
      in Amies transport medium streaked on a variety of culture media other than the
      conventional agar plates was also studied. Culturing of these swabs resulted in
      the detection of bacteria that are predominantly considered contaminants.

PMID- 21846009
TI  - Fluoroscopic exposure in modern spinal surgery.
AB  - The widespread use of minimally invasive and other spinal procedures raises
      concern about the peroperative radiation exposure to surgeon and patient. The
      authors noted the fluoroscopy time and the radiation dose, as read from the image
      amplifier, in 95 spinal procedures. The results of this prospective study varied
      widely between different operations. Percutaneous surgery was associated with
      more exposure than open surgery. For instance, the average radiation dose per
      pedicle screw was 3.2 times higher with percutaneous insertion than with an open
      approach. Therefore, efforts to reduce fluoroscopy time and radiation exposure
      should be made when using minimally invasive percutaneous surgical techniques.
      Preventive measures for the surgeon, such as lead aprons and gloves, thyroid
      shields, radioprotective glasses and staying away from the beam are recommended.
      Still from the surgeon's view-point, source inferior positioning of the image
      amplifier is indicated for the AP view, as well as monitoring of the radiation
      exposure. Finally, the difference in fluoroscopy time and radiation exposure
      between surgeons for the same procedure stresses the fact that peroperative
      radiation may be reduced by simple awareness and by training.

PMID- 21846010
TI  - The modified bone-patellar tendon-bone allograft in single-bundle anterior
      cruciate ligament reconstruction.
AB  - Bone-patellar tendon-bone graft has been an attractive option for single-bundle
      anterior cruciate ligament reconstruction in clinical practice. However, the
      graft-tunnel mismatch in the proximal part of the tibial tunnel and the ultimate
      strength after postoperative ligamentization process have been potential problems
      for the traditional 10-mm wide graft. We modified the traditional bone-patellar
      tendon-bone allograft to make it double-layer, as an ideal substitute graft for
      single-bundle anterior cruciate ligament reconstruction with better graft-tunnel
      match and higher initial graft strength.

PMID- 21846011
TI  - Combined arthroscopic techniques in the treatment of non-union of the anterior
      tibial spine.
AB  - We report a non-united tibial spine fracture with instability of the anterior
      cruciate ligament in a twenty-year-old soccer player. The patient underwent
      arthroscopy with debridement of scar tissue around the fracture site, reduction
      and fixation of the bony insertion of the ACL using screw and washer, and femoral
      notchplasty. More than one year after the initial surgery, the patient fully
      recovered knee stability and function. We have demonstrated that the additional
      problems caused by a non-union of a tibial spine fracture can be dealt with in
      one arthroscopic session.

PMID- 21846012
TI  - Intra-operative imaging technique to aid safe placement of screws in percutaneous
      fixation of pelvic and acetabular fractures.
AB  - Percutaneous internal fixation of pelvic fractures is becoming increasingly more
      popular among trauma surgeons worldwide due to reduced surgical related morbidity
      and facilitation of early mobilisation. Visualisation of the pelvic bony anatomy
      during percutaneous fixation is difficult, making the procedure technically
      demanding. We present a simple and easy intra-operative imaging technique that
      helps to confirm safe positioning of screws, particularly in the narrow anterior
      acetabular column, by use of radiopaque contrast medium to define the
      appropriately drilled track.

PMID- 21846013
TI  - Delayed fixation of displaced bilateral, atraumatic, femoral neck fractures in a
      patient with pregnancy related osteomalacia.
AB  - We present the case of a woman diagnosed with simultaneous displaced
      intracapsular femoral neck fractures following the birth of her second child. No
      traumatic event was identified. Diagnosis was delayed as the cause of her pain
      was thought to be non-skeletal in origin. Radiological and serological
      investigations were diagnostic of osteomalacia. Surgical fixation of her
      fractures was further delayed due to profound hypocalcaemia. Despite the delays,
      fixation with bilateral dynamic hip screws resulted in union with no evidence of
      avascular necrosis at 2 years follow-up. We believe this to be the first report
      of atraumatic bilateral femoral neck fractures and it shows that a good result
      can be achieved even in the presence of delayed fixation.

PMID- 21846014
TI  - Femoral prosthesis neck fracture following total hip arthroplasty: a case report.
AB  - Fracture of the femoral prosthesis neck following total hip arthroplasty is not
      common. We report a case of femoral prosthesis neck fracture in an adult male
      patient following modular, uncemented total hip arthroplasty. This case report
      further emphasizes the importance of the potentially high loading situation in
      the prosthetic femoral neck. On the other hand, the occurrence of a femoral
      prosthesis neck fracture in a cementless system denotes a well fixed distal stem
      and calls for a difficult revision procedure usually requiring an extended
      trochanteric osteotomy for stem retrieval.

PMID- 21846015
TI  - Massive recurrent tumoral calcinosis: a rare presentation.
AB  - Tumoral calcinosis is an autosomal recessive, metabolic disorder, characterised
      by deposition of calcium salts in the subcutaneous tissues of the body. We
      present a case of massive, recurrent tumoral calcinosis in a 32-year-old male
      patient.

PMID- 21846016
TI  - Vascular injury involving proximal medial-to-lateral oblique locking screw
      insertion in tibial intramedullary nailing.
AB  - Orthopaedic surgeons have reported increased neurologic complications with the
      employment of next-generation tibial nail fixation with variable proximal and
      distal locking options. However, vascular injury due to oblique screw placement
      has not been documented. We describe a case in which a medial-to-lateral oblique
      locking screw led to significant vascular injury. The judicious use of these
      screws and their relative contribution to fracture stability should be carefully
      considered for individual cases. Additionally, drill penetration through the far
      tibial cortex may not be obvious and utilizing oscillation or reverse drilling
      techniques may be of benefit. Lastly, the forward thrust of the popliteal artery
      with the use of a positioning bump in the popliteal fossa may place the vascular
      structure at increased risk of injury. Employing means to avoid these injuries
      and minimize risks in pertinent patients is of utmost importance.

PMID- 21846017
TI  - Trait anger as a mediator of difficulties with emotion regulation and female
      perpetrated psychological aggression.
AB  - Recent research has demonstrated the devastating impact of female-perpetrated
      psychological aggression in intimate relationships broadly and dating
      relationships specifically. With the perpetration of psychological aggression in
      dating relationships occurring at shockingly high rates, prevention programming
      for dating violence should target this form of aggression. Toward this end, it is
      important to understand the antecedent conditions that increase one's risk for
      perpetrating psychological aggression. This study sought to examine two possible
      risk factors for perpetrating psychological aggression among female
      undergraduates (N = 145), namely, emotion regulation and trait anger. Findings
      showed that difficulties with emotion regulation and trait anger were associated
      with increased psychological aggression perpetration, and trait anger mediated
      the link between emotion regulation and psychological aggression. Implications of
      these findings for prevention programming and future research are discussed.

PMID- 21846018
TI  - The efficacy of a high school rape prevention program in Israel.
AB  - Sexual violence against women and girls in Israel is rather prevalent. To address
      this problem, the Association of Rape Crisis Centers in Israel (ARCCI) provides
      rape prevention programs for middle to high school teens. These programs have
      been in place for several decades, but their effectiveness has not been evaluated
      empirically to date. This study seeks to fill this gap by performing an
      evaluation of one such preventive program. Three hundred and ninety-four 11th
      graders completed a preintervention and postintervention questionnaire, assessing
      their rape-related attitudes and behaviors. Results indicate a significant
      improvement following the workshop in the understanding of what distinguishes
      rape from mutually consensual relations, along with a substantial shift in many
      rape-supportive attitudes. At the same time, some victim blaming still remained.
      Likewise, self-reported behavioral changes were minimal, possibly because of a
      ceiling effect. Implications for future rape prevention programs in Israel are
      discussed.

PMID- 21846019
TI  - The influence of childhood maltreatment and self-control on dating violence: a
      comparison of college students in the United States and South Korea.
AB  - Various aspects of social learning and self-control theories have been applied to
      partner violence among multiple samples in the United States, but these
      theoretical approaches have been less commonly studied cross-culturally.
      Consequently, childhood maltreatment and low self-control have been identified as
      risk factors for various outcomes in primarily American samples. This study
      examined the relationships between childhood maltreatment, low self-control, and
      dating violence among college students in South Korea and the United States.
      Findings indicated that experiencing childhood maltreatment and having low self
      control were key predictors of perpetration and victimization for both
      psychological and physical relationship violence. Witnessing interparental
      violence during childhood was less consistently predictive of one's involvement
      in a violent dating relationship. Implications for theory and policy are
      discussed.

PMID- 21846020
TI  - Using the Internet to prescreen participants for research on interpersonal
      violence: experimental design considerations.
AB  - Internet-based testing has become increasingly popular in recent years due
      largely to the availability of computers and the Web to research participants.
      For researchers studying interpersonal violence, Internet-based methodologies can
      also be used as a prescreening device to identify a population of interest, such
      as individuals reporting violence in their relationships. However, several
      challenges exist with this approach. This article evaluates the use of an
      Internet-based prescreening device to identify potential participants for a study
      on interpersonal violence, highlighting challenges encountered with this
      methodology, and offers suggestions for improvement in experimental design when
      conducting Internet-based screenings of interpersonal violence.

PMID- 21846021
TI  - Victimization in young urban adults and depressed mood: understanding the
      interplay of coping and gender.
AB  - Violence exposure has a significant impact on victims' psychological well-being.
      This study examined the relationship between two types of violence exposures
      (threats and physical assaults), coping styles (emotion focused, avoidant, and
      problem focused), gender, and depression among 211 (147 females and 64 males)
      young urban adults (ages 18-24). Most participants (60%) endorsed being
      physically assaulted, whereas many (40%) endorsed being threatened. Hierarchical
      multiple regressions were conducted. As hypothesized, women reported using more
      emotion-focused coping and reported greater depression than men. Avoidant coping
      was a predictor for increased depression for both men and women. However, women
      who employed problem-focused coping after their first physical assault reported
      lower rates of depression. These findings have implications for designing early
      interventions.

PMID- 21846022
TI  - Intimate partner violence: the effect of gender and contextual factors on
      community perceptions of harm, and suggested victim and criminal justice
      responses.
AB  - Using a vignette to depict physical violence by an intimate partner, a 2
      (perpetrator gender) X 2 (participant gender) X 2 (frequency) X 2 (intent to
      cause harm) between subjects factorial design was used to examine under what
      circumstances individuals perceive: an incident should be illegal, the extent of
      harm, and appropriate victim and criminal justice responses. There were 868
      participants from the Brisbane (Australia) community (48.5% males). The actions
      of male perpetrators were viewed more seriously and the victims were recommended
      to seek more forms of assistance when the perpetrator was male. There were few
      differences in perceptions of violence according to participant gender. The
      frequency of the violence affected the participant's responses but the intentions
      of the perpetrator did not. Results are discussed in terms of stereotypes of
      intimate partner violence (IPV) and the implications for help-seeking behavior by
      victims.

PMID- 21846023
TI  - Female victimization and intimate partner violence after the May 12, 2008,
      Sichuan earthquake.
AB  - This study investigates the impact of the earthquake that occurred on May 12,
      2008 in Sichuan, China on stressed families already experiencing domestic
      violence. We hypothesized that cumulative postdisaster stress would increase
      marital aggression and that the well-being of victims would deteriorate following
      the quake. A total of 186 women were recruited for this study. Results show that
      all types of family violence, including psychological aggression and physical
      violence between partners, increased after the earthquake. We provided
      preliminary evidence that psychological aggression was significantly associated
      with the detrimental effects on victims' mental and physical functioning. The
      findings support the need for violence assessment among victims of earthquakes,
      and we recommend that violence prevention be considered as part of the
      intervention during such natural disasters.

PMID- 21846024
TI  - Children's appraisals as mediators of the relationship between domestic violence
      and child adjustment.
AB  - This study examines the relationships among variables that were likely to mediate
      the effects of exposure to domestic violence on children's internalizing problems
      (i.e., children's appraisals of domestic violence and their perceptions of family
      relationships). The study was conducted with 79 children exposed to domestic
      violence, including 41 boys and 38 girls, aged between 9 and 12 years old.
      Indicators used for children's appraisals of violence were attribution of blame
      and perceived threat. Children's perceptions of family relationships were based
      on their levels of parentification and the degree of their loyalty conflicts. A
      path analysis was used to verify the predictive model's pathways and to test the
      multiple mediator effects. Findings confirm the contribution of mediating
      variables and also reflect the association between self-blame and children's
      parentification. The results stress the relevance of evaluating the combined role
      of different potential mediators to provide a better understanding of the impact
      of domestic violence on children.

PMID- 21846025
TI  - [Combined injury of biliary ducts and vessels during cholecystectomy:
      peculiarities of clinical course and surgical tactics].
AB  - The results of treatment of 56 patients, in whom in 1984-2010 yrs, while
      performing cholecystectomy, a biliary duct injury have occurred, were analyzed,
      including 26 (main group)--with combined injury of biliary ducts and brunches of
      common hepatic artery, 30 (control group)--with isolated complete biliary ducts.
      High hepaticojejunostomy have constituted the main method of operation in a
      control group. In the main group in 2 patients there were attempts made to
      restore the arterial blood flow with subsequent performance of reconstructive
      intervention on biliary ducts. In 16 (61.5%) patients, due to adequate collateral
      blood supply presence, the bile outflow was restored using hepaticojejunostomy
      formation, and in 8 (30.8%)--hepatic resection of various volume was needed,
      because of hepatic abscesses formation. The results of treatment of patients in
      these groups have differed not essentially, while applying differentiated
      approach (positive results were achieved in 93.3 and 84.6% of patients,
      accordingly). So, in patients with combined injury of biliary ducts and branches
      of hepatic artery, while performance of cholecystectomy, it is necessary to apply
      multimodal tactics of treatment, taking into account the peculiarities of
      clinical course.

PMID- 21846026
TI  - [Application of esophagoplasty in cicatricial postburn esophageal stricture].
AB  - The results of the affected esophagus substitution, using a large intestine
      segment, in postburn stenosis in 42 patients were analyzed. Complete cicatricial
      esophageal impassability, impossibility or dangerous bougienage, rapid occurrence
      of the stricture recurrence, anamnesis data about perforation occurrence,
      presence of esophageal fistula have constituted the indications for the
      intervention performance. The best results were achieved while application of
      isoperistaltic retrosternal coloesophagoplasty, using left half of large
      intestine. The early postoperative complication was partial insufficiency of the
      neck anastomosis sutures and the late one--formation of its cicatricial
      stricture. Three patients died (postoperative lethality was 7.1%).

PMID- 21846027
TI  - [Efficacy of the immunomodulating therapy in complex treatment of gastric cancer
      complicated by acute hemorrhage using radical operations].
AB  - The results of radical operative treatment of 10 patients, suffering gastric
      cancer, complicated by an acute hemorrhage, using immunomodulating therapy, were
      presented. The immunomodulator application have promoted the natural cells
      killers cytological activity raising, the tumoral antigens (AG) elimination, as
      well as to enhance the neutrophils bactericidal and phagocytic activity, the
      circulating immune complexes (AG+IgG), (AG+IgM) formation and their deducing from
      an organism.

PMID- 21846028
TI  - [Enteral tube feeding of patients with duodenal ulcer before and after the
      operation].
AB  - The results of treatment of 947 patients, suffering duodenal ulcer stenosis, to
      whom the enteral nutrition (EN) probe was introduced before and after operation,
      were analyzed. There was noted a positive impact of EN on metabolic processes,
      water-electrolyte balance, lowering of operative-anesthesiologic risk, lethality
      and postoperative complications rate, securing possibility of operative
      intervention performance in a planned order.

PMID- 21846029
TI  - [Application of Sorbilact in the treatment and prophylaxis of postoperative
      intestinal paresis after reconstructive operations on the biliary ducts].
AB  - The activity of complex preparation Sorbilact was studied up in the patients,
      suffering obturative jaundice after surgical interventions on
      hepatopancreatoduodenal zone organs. Preparation Sorbilact causes antishock,
      proenergetic, desintoxication, diuretic and procinetic intestinal effects. The
      Sorbilact inclusion in complex of postoperative treatment of patients secures
      possibility of early administration of the enteral probe nutrition, promotes the
      trophic state optimization as well as the rehabilitation period duration
      shortening.

PMID- 21846030
TI  - [Application of the ASSES scale for the assessment of patient state severity and
      outcome prediction of acute pancreatitis].
AB  - There was estimated the severity state in 129 patients, suffering an acute
      pancreatitis, using the ASSES, SAPS, APACHE II and V. S. Savelyev's scales.
      Trustworthy differences of their values were established in survivors and the
      dead patients immediately after admitting to the hospital, before the operation,
      in 1-2 and 3-4 days after the operation. The best accuracy in predicting of
      outcome after the patient admittance to the hospital and in early postoperative
      period was noted while using the ASSES scale. The sum more than 13 points after
      admittance to the hospital and before the operation, as well as more than 16
      points on the first-second and the third-fourth postoperative days, according to
      the ASSES scale, witnesses unfavorable prognosis of the disease.

PMID- 21846031
TI  - [Application of penthrox preparation in patients with traumatic disease].
AB  - Indications for preparation Pentrox application in injured persons, suffering
      traumatic disease, were substantiated. The pain syndrome dynamics while
      conducting analgesia, was investigated, using simple verbal scale.

PMID- 21846032
TI  - [Ultrastructural changes of the capillary endotheliocytes in the muscle tissue of
      patients with chronic ischemia of the extremities after transplantation of the
      progenitor fetal liver cells].
AB  - Taking into account impossibility of reconstruction-restoration operations
      performance in cases of the distal arterial bed affection, it is necessary to
      find out and elaborate the methods of indirect revascularization. The cells
      transplantation performance for stimulation of reparation and angiogenesis in the
      affected extremity is considered a perspective direction of treatment. Essential
      stimulation of angiogenesis occurs after transplantation of progenitor stem cells
      of a fetal liver according to the data, obtained in experiment on laboratory
      animals. Later, transplantation of the cells was accomplished in patients with
      chronic ischemia of the extremities. Using method of electron microscopy of
      endotheliocvtes of the muscular tissue capillaries there was proved, that the
      cells transplantation causes essential stimulation of angiogenesis in patients,
      suffering chronic ischemia and constitutes a perspective method of indirect
      revascularization.

PMID- 21846033
TI  - [Actual issues of the surgery of elderly patients].
AB  - The results of 1516 operations, directed on complications prophylaxis and quality
      of life improvement, performed in 1004 senile patients, were analyzed. The
      expedience of application of epidural anesthesia in such patients was
      substantiated.

PMID- 21846034
TI  - [Cryosurgery, reloading and renewal].
AB  - The work constitutes an attempt to analyze and to determine the causes of
      problems concerning the cryosurgical methods of treatment development as well as
      the possible ways of their solving, Along with vivid progress in cryosurgical
      technologies taking place, cryosurgery is developing actively and need the
      conduction of profound scientific investigations in this field. It is possible to
      reveal a real potential of cryosurgery after scientific experimental--practical
      base creation, aiming at introduction of cryosurgical methods in a full volume
      into clinical medicine.

PMID- 21846035
TI  - [Application of combined videothoracoscopic resection in thoracic surgery].
AB  - The method of combined videothoracoscopic atypical pulmonary resection,
      permitting to apply endostaplers and standard staplers in one intervention
      procedure, was elaborated. The method was applied in 47 patients in various
      pulmonary diseases without severe complications, all the patients are alive.
      Economic expedience of the method application, permitting to reduce usage of
      endostaplers, was shown.

PMID- 21846036
TI  - [Treatment of purulent wounds using vacuum-therapy].
AB  - The results of treatment of complex wounds in 115 patients, in 56 of whom vacuum
      therapy was conducted, were analyzed. The duration of a bandage holding
      constitutes 1 - 3 days at average. The peculiarities of clinical course, the
      dynamics of the wounds microbic spillage, cellular content in the wounding
      prints, phagocytic activity and phagocytic number, the phagocytosis completeness
      index were estimated and calculated. Application of vacuum-therapy have promoted
      the earlier cleansing and epithelization of the wounds as well as the tissues
      reparation occurrence and the laboratory indices normalization.

PMID- 21846037
TI  - [Application of the puncture-drainage interventions under ultrasonographic
      control in the treatment of pancreatic pseudocysts].
AB  - Results of the puncture-drainage interventions under ultrasonographic
      investigation in the treatment of 100 patients, suffering pancreatic gland
      pseudocysts in various stages of its formation, were presented. The data obtained
      witness the method efficacy, permitting to achieve, in complex of treatment,
      reconvalescence of 74.7% patients, while external drainage application, and of
      26.9%--while puncture sanation performance.

PMID- 21846038
TI  - [Observation of thoracoabdominal wounds with damage of the rectum, sigmoid colon
      mesentery, penetrating wounds of the stomach, spleen and left hemidiaphragm].

PMID- 21846039
TI  - [Observation of the ascending colon evagination through cecostoma].

PMID- 21846040
TI  - [The pancreatic gland stump processing using high-frequency ablation: simple,
      rapid, safe].

PMID- 21846041
TI  - [The message about unreliability of publications].

PMID- 21846042
TI  - [Influence of some environmental factors in urban areas on public health (review
      of literature)].
AB  - The authors present results of studies concerning influence of environmental
      factors in urban areas on public health. Modern men indoors and outdoors are
      exposed simultaneously to multiple hazards with levels sometimes exceeding
      physiologic tolerance, and some of these hazards could be assigned to risk
      factors. Preventive medicine requires new theoretic basis for prophylactic
      activities grounded on medical ecologic and biologic views explaining cause
      effect relationships between mechanisms of human health in connection with
      environmental hazards.

PMID- 21846043
TI  - [Climate and ecologic state of urban areas in Eastern Kazakhstan].
AB  - Ust-Kamenogorsk territory was demonstrated to have climate peculiarities
      depending on local relief and unfavorable wind conditions of ventilation, that
      could promote formation of highly chemically loaded zones. Suggested evaluation
      methods provide qualitative and quantitative assessment of climate parameters for
      individual areas of residence. Marking areas according to residence comfort for
      population, based on analysis of geographic position of the studied territory, in
      accordance with repetition of meteorologic processes, could specify major factors
      influencing climate on urban territories of modem Kazakhstan cities.

PMID- 21846045
TI  - [Problem of noise as an ecologic factor on urban territories].
AB  - The authors evaluated levels of transport noise in intensive automobile traffic
      of Ust-Kamenogorsk. Noise on traffic area appeared to spread not only onto the
      area nearing the road, but deeply into housing blocks. Thus, the area exposed to
      the most severe noise covers blocks and districts situated along highways of
      citywide importance. Reasons of high noise level are: blocks and districts are
      not isolated from noise passing from highways, greenery planting is insufficient,
      most territories intended for recreation and children playgrounds are used for
      traffic.

PMID- 21846044
TI  - [Hygienic evaluation of ambient air pollution in Ust'-Kamenogorsk].
AB  - The article deals with hygienic evaluation of Ust-Kamenogorsk ambient air
      pollution with nitrogen dioxide, carbon dioxide, phenol and suspended solids.
      Ambient air samples were taken in 36 points over 3 days at 6 am, noon, 6 and 9 pm
      (local time) during warm season (August) and cold season (December). According to
      the results obtained, the authors divided Ust-Kamenogorsk territory into 2 areas,
      based on IAP4 (index of air pollution): conditionally dirty area--over 7;
      conditionally clean area--under 7. Findings are high pollution with suspended
      solids, nitrogen dioxide, sulphur dioxide and phenol over all territory of the
      city. But "conditionally dirty" area demonstrated the highest level of ambient
      air pollution.

PMID- 21846046
TI  - [Monitoring public health state in solving ecologic problems of cities].
AB  - The article covers morbidity and demographic changes in inhabitants of
      territories subjected to high geochemical load, exemplified by Ust-Kamenogorsk of
      East Kazakhstan region over 2005-2009. The authors revealed some unfavorable
      trends in medical and social processes in the region. The most sensitive to
      anthropogenic pollution are: infant mortality, general morbidity among
      adolescents and children, primary morbidity among children and adults, when
      compared to the reference area (Shiutchinsk).

PMID- 21846047
TI  - [Microelemental and cytologic state of children in urban areas].
AB  - Microelemental and cytomorphologic studies among preschoolers living in East
      Kazakhstan revealed accumulation of toxic metals (lead, mercury, cadmium) in hair
      and lower essential microelements (copper, selenium) in urine, increased number
      of cells with vacuole dystrophy, phagocyted, apoptotic (residual bodies) and
      degenerated cells, mastocytes, acaryotes in nasal and buccal epithelium.
      Noninvasive studies (of hair, urine, nasal and buccal epithelium) are sensitive,
      informative and prognostically valuable tests for diagnosis of ecologically
      dependent disorders.

PMID- 21846048
TI  - [Comparative evaluation of morbidity in Temirtau and Shiutchinsk].
AB  - The authors compared morbidity among residents of Temirtau near influence of iron
      industry enterprises, with Shiutchinsk situated in resort area was taken as a
      reference region. The morbidity was studied through retrospective analysis over
      2005-2009. The study over the 5 years proved steady 1.1-1.4 times increase of
      general morbidity level. Major entities increased were ophthalmologic diseases,
      circulatory system and endocrine diseases. Incidence structure among urban adults
      was presented by leading circulatory and respiratory diseases, significant place
      was occupied by ophthalmologic diseases, digestive system diseases, nervous
      system and locomotory system diseases.

PMID- 21846050
TI  - [Contemporary state and prospects of occupational pathologic service in
      Kazakhstan].
AB  - Present healthcare care system in Kazakhstan Republic does not provide priority
      medical and sanitary care for workers, so measures on medical management and
      health protection for workers are necessary. One of the main priorities in
      governmental activities of Karakhstan Republic is health care system--an
      integral, developed, socially oriented system providing availability, quality,
      oportuneness and continuity of medical care. That necessitates elaboration of
      Strategy Management Plan in occupational pathology and progressive model of
      Occupational Therapy service in Kazakhstan.

PMID- 21846049
TI  - [State of clinical and neurologic condition of Temirtau inhabitants].
AB  - The article covers results of studies concerning psychologic and clinical
      neurologic state of Temirtau inhabitants. Early clinical forms of cerebro
      vascular diseases were more frequent among males, but cryptogenic
      encephalopathies were more prevalent among females. Among the males examined, the
      early clinical signs of cerebro-vascular diseases were seen in all age groups,
      more often at the age of 20-29. Among the females, cryptogenic encephalopathies
      were more often at the age over 40. Early clinical forms of cerebro-vascular
      diseases and cryptogenic encephalopathies were associated with asthenic, astheno
      hypochondriac, astheno-depressive syndrome and vegetative dysfunction syndrome.
      The group with early clinical signs of cerebro-vascular diseases was
      characterized by prevalent asthenic syndrome, but the cryptogenic encephalopathy
      group had more often astheno-hypochondriac syndrome.

PMID- 21846051
TI  - [Evaluating occupational conditions of communication operators as professional
      users of videodisplay terminals].
AB  - The article present analysis of data concerning hygienic evaluation of telephone
      and communication operators in "Kazakhtelekom" corporation of Karaganda, who use
      vidiodisplay terminals in occupational activities. Complex of occupational
      hazards revealed--discomfortable microclimate, inadequate illumination, higher
      levels of noise and electromagnetic rays--determines occupational health risk for
      videodisplay terminal users. The authors specified and implemented measures on
      preserving performance and health (change of videodisplay terminal, increase of
      workplace square, occupational exercises).

PMID- 21846052
TI  - [Ageing pace in workers engaged into chromium ores processing].
AB  - The authors revealed premature ageing pace in risk group occupations engaged into
      chromium ores processing. Major occupations with increased ageing pace vs.
      population standard are defined. The studies proved that such occupations as
      "furnace operator", "feeder", "refractory gunman" have ageing pace increased to 5
      10 years in accordance with age and length of service in hazardous conditions.
      Such changes promotes health disorders marked by more frequent chronic diseases
      and general morbidity with transitory disablement.

PMID- 21846053
TI  - [Immune homeostasis parameters in chromium production workers].
AB  - The authors studied immune homeostasis parameters in chromium production workers
      and presented changes in cellular, humoral immunity and sensibilization to
      chromium in main occupational groups of workers. Findings are that occupational
      contact with chromium compounds results in T-immune deficiency. Allergic tests
      also revealed higher sensibilization to 6-valent chromium.

PMID- 21846054
TI  - [Medical rehabilitation efficiency in chronic dust bronchitis patients].
AB  - Medical examination covered 41 workers with long length of service in coal and
      mining industry, diagnosed as having "Chronic obstructive dust bronchitis", who
      received a complex of therapeutic and prophylactic measures including traditional
      broncholytic therapy, physical therapy and exercise therapy. 20 patients of main
      group received additional complex "Vobenzyme + Vitrum + herbal tea + aeration".
      Efficiency of medical rehabilitation was assessed through external respiration
      parameters--maximal effect was seen among the main group members (reliable
      increase of forced vital capacity, peak flow and maximal flow at 25% forced vital
      capacity).

PMID- 21846055
TI  - [Influence of hyperhomocysteinemic on the wavelet-analysis of cerebral blood
      flow].
AB  - The objective of this study is to assess the effect of different blockers of a
      vessel tone on the cerebral blood flowmotion in rats using spectral analysis
      based on wavelets transform of the periodic oscillations of the cerebral laser
      Doppler flowmetry signal. Three frequency intervals were identified (0.01-0.04
      Hz, 0.04-0.126 Hz, 0.126-0.4 Hz) corresponding to endothelial, neurogenic and
      myogenic origins. It was increase of amplitude in endothelial interval during
      acute hyperhomocysteinemie. We suppose that modulation factors form the value of
      cerebral flow which supports on constant level during autoregulation.

PMID- 21846056
TI  - [The answer reaction of system complement on correction of hypoxia of hydazepam
      and succinic acid].
AB  - Investigated functionally activation of human complement in vivo an model of high
      hypoxia (6-7,5 km) as without correction, so at the phone of medicine hydazepam
      and succinic acid. Discover that by analysis of the sensitive to complement
      components one can estimate effects of high hypoxia and her pharmacological
      correction.

PMID- 21846057
TI  - [Application of alpha-tocopherol acetate prevents swelling of brain slices during
      the autoblood clot action].
AB  - The swelling of olfactory cortex slices of the hypertensive SHR rats under the
      long autoblood action have been studied. The influence of a preincubation of
      slices with vitamins E, C and D on a degree of swelling have been detected by
      their weighing before and after exposure to autoblood. The water-soluble form of
      vitamin E have exerted a substantial antiswelling action exceeding the same of
      vitamin D, whereas vitamin C had no any effect.

PMID- 21846058
TI  - [Inotropic reaction of myocardium rats with postinfarction and diabetic
      remodeling on extrasistolic influences].
AB  - Studied inotropic reaction papillary muscles of rats with postinfarction and
      diabetic remodeling on extrasistolic influences. It was found, that excitability
      of myocardium rats raises at a diabetes induced streptozotocin. Postextrasistolic
      contraction of myocardium rats with postinfarction cardiosclerosis it was
      considerably oppressed, and rhythmoinitropic reaction of myocardium rats was
      comparable to reaction of intact myocardium at a diabetes induced streptozotocin.
      The combination postinfarction and diabetic influence is paradoxical promoted
      preservation postextrasistolic potentiation of myocardium rats.

PMID- 21846059
TI  - [The time analysis of distribution cardio intervals at loading testing].
AB  - On the basis of the analysis of distribution cardio intervals received at loading
      testing, it's modeling and time criteria causing adaptable potential and
      describing a vegetative homeostasis during the loading and regenerative periods
      are determined.

PMID- 21846060
TI  - [Pathogenetic aspects of proteolysis and hemorrhagic pancreatonecrosis and
      methods of their correction].
AB  - In the work you can find the results of the research on modeling of acute
      experimental pancreatitis caused by injecting solution of tripsin and vipera
      berus venom. All the visceral organs are involved, that corresponds to common to
      the human and animal pathological processes (induction of proteolysis and DIC
      syndrome). The results of the research show and prove the effectiveness of
      sandostatin and anti-ophidic serum influence on the proteolytic processes, blood
      coagulation. Thus, this research gives the opportunity to possibly expand the
      usage of sandostatin and anti-ophidic serum on treatment diseases with the
      participation of cascade proteolytic processes.

PMID- 21846061
TI  - [Formation of the compensation answer in the system "lipid peroxidation -
      antioxidant protection" in rats with alimentary dislipidemia].
AB  - It is investigated conditions of system "lipid peroksidation - antioxidant
      protection" at rats of the line Wistar at prolonged formation alimentary
      dyslipidemia (DLP). It is established, that at formation DLP during 46 days in
      cells there was no increase in resistance and capacity of processes antioxidant
      protection. In prolonged DLP (90 days) was characterized by occurrence of the
      compensation-adaptive answer in the system "lipid peroksidation - antioxidant
      protection".

PMID- 21846062
TI  - [Trigger mechanism of neuroprotective effect of ischemic preconditioning].
AB  - Analysis of literature data indicates that adenosine, glutamate, NO, reactive
      oxygen species, erythropoietin, interleukin-1 are triggers of delayed
      preconditioning of brain. The issue of involvement of bradykinin, opioids, TNF
      alpha in preconditioning remains unclear, although possibility of these compounds
      to induce a state of increased tolerance to ischemia does not induce a doubt. It
      was established that adenosine receptor agonists, bradykinin, opioids, NO* donors
      can mimic a phenomenon of early preconditioning.

PMID- 21846063
TI  - [Determination of reduced homocysteine fraction in blood plasma with HPLC-MS].
AB  - Homocysteine is a bioactive compound involved in many impotant processes of
      clinical significance. High sensitivity methods associated with preparation of
      oxidation-resistant derivatives are of demand for determination of different
      homocysteine fractions. In this work a derivatization agent N-ethylmaleinimide
      (NEM) was proposed by us for detection of reduced homocysteine fraction with HPLC
      MS. Linearity, detection limit, and precision were 25-1500 nM, 10 nM, and 95-105%
      respectively, with reproducibility within 12%.

PMID- 21846064
TI  - [Prospective survey of erectile dysfunction after external beam radiotherapy for
      prostate cancer].
AB  - OBJECTIVE: We prospectively evaluated the effect of external beam radiotherapy on
      erectile function in patients with localized or locally advanced prostate cancer
      using the Japanese version of the International Index of Erectile Function (IIEF)
      survey. PATIENTS AND METHODS: From 2000 to 2007, we identified 55 patients who
      underwent external beam radiotherapy at our institution for localized or locally
      advanced prostate cancer and could respond to the IIEF survey. The patients did
      not receive neo- and/or adjuvant hormone therapy and they were followed-up for at
      least 12 months after radiotherapy. Mean patient age was 69 years and the mean
      PSA level before radiotherapy was 24.9 ng/ml. RESULTS: First we evaluated the
      change of the erectile function domain score over time before and after
      radiotherapy. The population of severe erectile dysfunction (ED) increased while
      those with no or mild ED decreased after radiotherapy. The erectile function and
      intercourse satisfaction domain score of the IIEF declined significantly after
      radiotherapy, however, the orgasmic function, sexual desire, and overall
      satisfaction domain scores did not change after external beam radiation. Of the
      34 patients who had erectile function at baseline, 10 patients could maintain
      erectile function 12 months after radiotherapy. Though there were no significant
      differences in clinical features between patients who could maintain erectile
      function and those who had worsening erectile function 12 months after
      radiotherapy, the sexual desire domain score before radiotherapy was
      significantly higher in patients who could maintain erectile function than their
      counterparts. CONCLUSION: Using the IIEF survey, external beam radiation was
      found to affect erectile function in patients with localized or locally advanced
      prostate cancer.

PMID- 21846065
TI  - [Predictors of operative blood loss in patients undergoing small incision radical
      prostatectomy].
AB  - We performed 82 cases of small incision radical prostatectomy from July, 2003 to
      September, 2009. There were 38 cases of cT1c, 41 cases of cT2, and 3 cases of
      cT3. Mean operative time was 222 +/- 31.7 (min.). Mean operative blood loss was
      1,232 +/- 583 (ml). We evaluated factors predicting operative blood loss, such as
      prostate volume, body mass index (BMI), age, and preoperative PSA level. Group
      with smaller prostate volume and group with lower BMI showed significantly less
      blood loss compared to that of a higher group (p = 0.0009, p = 0.0014,
      respectively). Multivariate analysis showed that prostate volume and BMI were
      significant predictors for operative blood loss (p = 0.0005, p = 0.0122,
      respectively). Prostate volume and BMI may be a useful predictor for operative
      blood loss.

PMID- 21846066
TI  - [Cholesterol granuloma of the kidney: a case report].
AB  - A 58-year-old woman was referred to our outpatient clinic for further examination
      of a mass detected in the right kidney on follow-up ultrasonography performed for
      active surveillance of right ovarian cancer. Ultrasonography and computed
      tomography showed a cyst (diameter, 30 mm) with an irregular wall in the middle
      of the right kidney. Right nephrectomy was performed since malignancy was
      suspected. Histological findings of the mass indicated cholesterol granuloma.
      Although cholesterol granulomas in the middle ear have been frequently reported,
      those in other organs have been reported in few studies. In this patient, the
      cholesterol granuloma could be barely distinguished from the cancer by using
      imaging techniques.

PMID- 21846067
TI  - [A case of renal malacoplakia that was difficult to distinguish from cystic renal
      cell carcinoma].
AB  - A 66 years old man visited our hospital with a chief complaint of right flank
      pain and abdominal palpable mass. Abdominal enhanced computed tomography scan
      showed a large cystic mass with infiltrating surrounding tissue in the right
      kidney. We diagnosed it infected cystic renal cell carcinoma because of high
      grade fever and acute inflammatory response. It was surgically unresectable
      tumor. Therefore, percutaneous puncture and drainage was performed under
      ultrasound guidance. In the culture of drainage fluid, Escherichia coli (E. coli)
      was isolated. Then, we confirmed reduction in the size of the tumor, right
      radical nephrectomy was performed. Because of tumor invasion to ascending colon,
      we performed the excision of right kidney together with ascending colon.
      Histological study confirmed target-shaped Michaelis-Gutmann body, and the
      definitive diagnosis was malacoplakia of the kidney. We reported a case of renal
      malacoplakia that was difficult to distinguish from cystic renal cell carcinoma.
      Our case is 12th case of renal malacoplakia in the Japanese literature.

PMID- 21846068
TI  - [Renal allograft rupture attributed to coughing while asleep: a case report].
AB  - Renal allograft rupture (RAR) is a rare but serious complication of renal
      transplantation. The most common cause of RAR is acute rejection but other causes
      have increased in frequency with advances in immunosuppressive therapy. We report
      a patient with RAR attributed to coughing while asleep. A 53-year-old male
      received a living-donor renal transplantation for end-stage renal failure due to
      diabetic nephropathy. The clinical course was satisfactory, and he was discharged
      on the 12th postoperative day with a serum creatinine level of 1.24 mg/dl. On the
      24th morning, he felt sudden swelling and pain over the incision area soon after
      a big cough. Ultrasound and computed tomography revealed a perinephric hematoma.
      Emergency surgical exploration showed complete laceration of the abdominal fascia
      and 4-cm rupture at the anterolateral aspect of the kidney. High intra-abdominal
      pressure when coughing had torn the fascia, and the graft appeared to have
      ruptured under the fascial tension. Bleeding was controlled with a polyglactin
      910 2/0 mattress parenchymal suture enforced with application of a fibrin tissue
      adhesive collagen fleece. Twelve months after the repair, the patient's renal
      function was stable with a serum creatinine level of 1.3 mg/dl.

PMID- 21846069
TI  - [A case of prednisolone therapy for radiation-induced hemorrhagic cystitis].
AB  - Hemorrhagic cystitis resulting from radiation to pelvic visceral malignant
      lesions often might be incurable and there have been no established definitive
      treatment. We experienced a case with severe radiation-induced hemorrhagic
      cystitis refractory to conventional therapy. The treatment with oral
      administration of prednisolone was performed and obtained a successful result.
      Gross hematuria disappeared in 2 weeks in this case. This experience suggested
      that oral administration of prednisolone could be considered the treatment for
      patients with radiation-induced hemorrhagic cystitis when usual treatments
      including transurethral electro-coagulation are unsuccessful.

PMID- 21846070
TI  - [Intravesical migration of intrauterine contraceptive device (IUCD) with stone
      formation].
AB  - Migration of an intrauterine contraceptive device (IUCD) into the bladder and
      secondary stone formation are uncommon complications associated with the
      insertion of IUCD. To our knowledge, there have been no such reported cases in
      Japan. In the present report, we describe the case of a 59-year-old woman who
      underwent an operation for the removal of an IUCD from the bladder, which had
      been inserted 30 years ago. The patient was referred to our facility because of
      hematuria and recurrent urinary tract infections. A plain film revealed a
      calcified mass in the pelvis, and cystoscopy revealed a fully mobile calculus in
      the bladder. During a transurethral cystolithotripsy, the IUCD was found within
      the calculus and removed transurethrally. No fistulae or defects were found in
      the bladder wall.

PMID- 21846071
TI  - The future of gerontological nursing.
AB  - Spring 2010 marked the passage of the Patient Protection and Affordable Care Act;
      however, soon after this landmark legislation passed, legal and political
      challenges ensued to change key features of the law. In this environment of
      proposed changes to transform the U.S. health care system, the Institute of
      Medicine released its report titled The Future of Nursing: Leading Change,
      Advancing Health in October 2010. The groundbreaking consensus report calls for a
      transformation of nursing at practice, education, and leadership levels. This
      article briefly summarizes findings and key recommendations with an emphasis on
      areas most relevant to the future of gerontological nursing. In addition, various
      implementation actions promoted through the Robert Wood Johnson Foundation's
      Future of Nursing Campaign and the AARP Center to Champion Nursing are discussed
      to encourage gerontological nurses to participate in current and future debates.

PMID- 21846072
TI  - Readiness for practice: the senior practicum experience.
AB  - Nursing students must be prepared to enter the practice environment ready to
      competently care for patients. The purpose of this study was to examine factors
      hypothesized to influence senior nursing students' perceptions of readiness for
      practice and to determine their level of comfort performing skills independently.
      This study also validates an investigator-developed instrument, the Casey-Fink
      Readiness for Practice Survey. Factor loading indicated four components tested by
      subscales in the survey: clinical problem solving, learning techniques,
      professional identity, and trials and tribulations. The greatest challenges
      reported by students were managing multiple patient care assignments,
      communicating with physicians, and caring for dying patients. Clinical
      competency, role development, and career planning support were areas in which
      students desired more assistance during their senior practicum course. Most
      survey respondents voiced confidence in their ability to problem solve and felt
      ready to assume the professional nursing role.

PMID- 21846073
TI  - Structural and psychological empowerment and reflective thinking: is there a
      link?
AB  - Baccalaureate nursing education prepares students to become registered nurses in
      evolving health care systems. During their program, students' perceptions of
      empowerment in the nursing profession begin to form, and they are introduced to
      the process of reflective thinking. The purpose of this integrative literature
      review is unique in that three concepts are examined and linked-structural
      empowerment (as conceptualized by Kanter), psychological empowerment (as
      described by Spreitzer), and reflective thinking (as characterized by Mezirow)
      and a theoretical model for testing is proposed. In examining the conceptual
      links, it is apparent that all three are required for learning and nursing
      practice. By preparing students to be empowered, reflective professionals, it is
      proposed that they will be more effective in their academic and future practice
      work. The conceptual links and proposed model described in this article provide
      the foundation for building a body of evidence to support or refute this
      contention.

PMID- 21846074
TI  - Concept mapping a baccalaureate nursing program: a method for success.
AB  - The understanding of curricular design and development is paramount for faculty.
      For novice faculty, learning teaching methods commonly takes precedence over
      understanding curriculum development. Professional accrediting bodies of nursing
      programs require curriculum course content to be pertinent and flow logically.
      Baccalaureate nursing programs can choose to be accredited by the Commission on
      Collegiate Nursing Education. The purpose of this article is to describe an
      educational innovation that one College of Nursing implemented to orient new
      faculty to the curriculum and prepare for an accreditation renewal. Assigned
      faculty developed and implemented a concept mapping process aimed to evaluate and
      revise course content based on national standards and guidelines. Undergraduate
      faculty understanding and ownership of the curriculum was evident throughout the
      process. The concept mapping process proved to be an innovative approach to
      enhance the curriculum and equip faculty with an understanding of the
      relationship between concepts and course content.

PMID- 21846075
TI  - Publication bias and outcome reporting bias: agomelatine as a case example.
AB  - Publication bias and outcome reporting bias contribute to distorted perceptions
      of drug efficacy and the underreporting of adverse events. To demonstrate these
      biases, this article describes how the clinical profile of the antidepressant
      agent agomelatine (Valdoxan((r))) has been presented in the literature.
      Agomelatine has been systematically assessed in 10 short-term placebo-controlled
      studies and three long-term placebo-controlled relapse prevention studies. Five
      published trials demonstrated clinically modest but statistically significant
      benefits over placebo. Five unpublished trials did not find agomelatine more
      effective than placebo, but in two of these studies the active comparison drug
      (fluoxetine [Prozac((r))] or paroxetine [Paxil((r))]) was more effective than
      placebo. Agomelatine was more effective than placebo in one of three relapse
      prevention studies, but only the positive study was published. Based on what is
      evident in the entire published and unpublished dataset, agomelatine does not
      have a tremendously superior sleep and sexual effects profile. The risk of liver
      toxicity is also not prominently highlighted in the published literature.

PMID- 21846077
TI  - Baby Boomers: are we ready for their impact on health care?
AB  - As the first of the Baby Boomer generation turns 65 this year, there is rising
      fear that a crisis awaits related to many mental health resources. This article
      describes the characteristics of Baby Boomers, their future mental health needs,
      and the extent of the impending insufficiency of mental health resources to meet
      those needs. Recommendations to address the unprecedented mental health demands
      of this generation are presented.

PMID- 21846076
TI  - Outcomes of parental mental illness on children: a qualitative study from Iran.
AB  - Children of parents with mental illness are a substantial, yet marginalized
      group. This study, as part of a more extensive research project, used grounded
      theory to explore the outcomes of parental mental illness on their children.
      Seventeen informants were interviewed at a mental hospital in the city of Qazvin,
      Iran. The participants were selected using purposeful and theoretical sampling.
      Interviews were analyzed using Strauss and Corbin's method. It was revealed that
      parental mental illness leads to five major outcomes that involve communication,
      mental, educational, economic, and extra roles factors. As such, it is suggested
      that these children should be considered within health care plans and that policy
      makers, nurses, and other health care providers use these findings for preventive
      and educational purposes.

PMID- 21846078
TI  - Grief and loss of a caregiver in children: a developmental perspective.
AB  - Grief is one's response to loss. Each person's expression of grief is unique and
      influenced by factors such as age, culture, and previous exposure to loss.
      Whether or not children grieve has been debated, with some proponents stating
      that children do not grieve at all until they are adolescents, and others
      asserting that infants are capable of grief. The most common conclusion is that
      children of all ages do grieve, although their grief is different from that of
      adults. Children's grief is also closely related to developmental stage, so
      children of varying ages also grieve differently. Therefore, supporting a
      grieving child is relative to his or her stage of development. For this reason,
      it is important for practitioners working with grieving children to understand
      the manifestations of grief at various developmental stages, to provide competent
      support to children of all ages who experience loss.

PMID- 21846079
TI  - Sleep deprivation: consequences for students.
AB  - During the adolescent years, a delayed pattern of the sleep-wake cycle occurs.
      Many parents and health care providers are not aware that once established, these
      poor sleep habits can continue into adulthood. Early school hours start a pattern
      of sleep loss that begins a cycle of daytime sleepiness, which may affect mood,
      behavior, and increase risk for accidents or injury. These sleep-deprived habits
      established in adolescence can often lead to problems during college years. Sleep
      hygiene can be initiated to help break the cycle, along with education and
      implementation of a strict regimen. Monitoring all adolescents and college-aged
      students for sleep insufficiency is imperative to improve both academic and
      emotional well-being.

PMID- 21846080
TI  - Another face of health care disparity: stigma of mental illness.
AB  - In many everyday situations, individuals with mental illness face stigma that
      leads to discrimination. A growing body of evidence suggests that those with
      mental illness experience disparities in health care and that their medical needs
      are often overlooked. The purpose of this article is to increase awareness to
      this problem. Fictional vignettes in which individuals with mental illness seek
      medical care are presented, followed by discussion on the role discrimination may
      play in the level of care these patients received. To help alleviate disparities,
      nurses are encouraged to advocate and speak out when they suspect discrimination
      is affecting the quality of care of those with mental illness.

PMID- 21846081
TI  - Aging in place versus nursing home care: comparison of costs to Medicare and
      Medicaid.
AB  - The objective of this study was to compare the community-based, long-term care
      program called Aging in Place (AIP) and nursing home care, in terms of cost to
      the Medicare and Medicaid programs. A retrospective cohort design was used in
      this study of 39 nursing home residents in the Midwest who were matched with 39
      AIP participants. The AIP program consisted of a combination of Medicare home
      health, Medicaid home and community-based services (HCBS), and intensive nurse
      care coordination. Controlling for high inpatient Medicare cost in the 6 months
      prior and the 10 most frequently occurring chronic conditions, multiple
      regression was used to estimate the relationship of the AIP program on Medicare
      and Medicaid costs. Total Medicare and Medicaid costs were $1,591.61 lower per
      month in the AIP group (p < 0.01) when compared with the nursing home group over
      a 12-month period. The findings suggest that the provision of nurse-coordinated
      HCBS and Medicare home health services has potential to provide savings in the
      total cost of health care to the Medicaid program while not increasing the cost
      of the Medicare program.

PMID- 21846082
TI  - Highly enantioselective intermolecular Stetter reactions of beta-aryl acceptors:
      alpha-ketoester moiety as handle for activation and synthetic manipulations.
AB  - The use of beta,gamma-unsaturated-alpha-ketoesters in the intermolecular Stetter
      reaction furnishes 1,2,5-tricarbonyl compounds in high yield and excellent
      enantioselectivity. The alpha,delta-diketoesters generated using this methodology
      serve as useful synthetic building blocks via chemo- and diastereoselective
      transformations.

PMID- 21846083
TI  - Ideal rate of collision of cylinders in simple shear flow.
AB  - The collision of particles influences the behavior of suspensions through the
      formation of aggregates for adhesive particles or through the contributions of
      solid-body contacts to the stress for nonadhesive particles. The simplest
      estimate of the collision rate, termed the ideal collision rate, is obtained when
      particles translate and rotate with the flow but have no hydrodynamic or
      colloidal interactions. Smoluchowski calculated the ideal collision frequency of
      spherical particles in 1917. So far, little work has been done to understand rate
      of collision for nonspherical particles. In this work, we calculate the ideal
      collision rate for cylindrical particles over a broad range of particle aspect
      ratios r defined as the ratio of length to diameter. Monte Carlo simulations are
      performed with initial relative positions and orientations that model the rate of
      approach of noninteracting particles following Jeffery orbits with several
      choices of the orbit distribution. The role of rotational motion of particles on
      collision frequency is elucidated by comparing the ideal collision rate
      calculations with similar calculations for nonrotating particles. It is shown
      that the ratio of the collision rate of cylinders to that of spheres that
      circumscribe the cylinders is proportional to 1/rr(e) for r ? 1 and r(e) for r ?
      1. Here, r(e) is the effective aspect ratio defined as the aspect ratio of a
      spheroid having the same period of rotation as the cylinder. The effective aspect
      ratio of the cylindrical particles was determined using finite element
      calculations of the torque on nonrotating cylinders with their axes parallel to
      the velocity and velocity gradient directions. In addition to deriving the total
      collision rate, we categorize collisions as side-side, edge-side, and face-edge
      based on the initial point of contact. Most collisions are found to be side-edge
      for r ? 1 and face-edge for r ? 1, suggesting that nonlinear aggregates will
      develop if particles stick at the point of first contact.

PMID- 21846084
TI  - CH...O hydrogen bonds in "clicked" diketopiperazine-based amide rotaxanes.
AB  - Two amide [2]rotaxanes were synthesized in high yields using a novel N,N'
      dipropargyl diketopiperazine axle centerpiece as the template to which the
      stoppers are attached through "click chemistry". (1)H and 2D NMR spectra provide
      evidence for two different H-bonding motifs, in one of which the triazole CH
      groups form C-H...O?C bonds with the wheel carbonyl O atoms. This motif can be
      controlled and switched reversibly by competitive anion binding.

PMID- 21846085
TI  - Investigating the interaction of cellulose nanofibers derived from cotton with a
      sophisticated 3D human lung cell coculture.
AB  - Cellulose nanofibers are an attractive component of a broad range of
      nanomaterials. Their intriguing mechanical properties and low cost, as well as
      the renewable nature of cellulose make them an appealing alternative to carbon
      nanotubes (CNTs), which may pose a considerable health risk when inhaled. Little
      is known, however, concerning the potential toxicity of aerosolized cellulose
      nanofibers. Using a 3D in vitro triple cell coculture model of the human
      epithelial airway barrier, it was observed that cellulose nanofibers isolated
      from cotton (CCN) elicited a significantly (p < 0.05) lower cytotoxicity and (pro
      )inflammatory response than multiwalled CNTs (MWCNTs) and crocidolite asbestos
      fibers (CAFs). Electron tomography analysis also revealed that the intracellular
      localization of CCNs is different from that of both MWCNTs and CAFs, indicating
      fundamental differences between each different nanofibre type in their
      interaction with the human lung cell coculture. Thus, the data shown in the
      present study highlights that not only the length and stiffness determine the
      potential detrimental (biological) effects of any nanofiber, but that the
      material used can significantly affect nanofiber-cell interactions.

PMID- 21846086
TI  - Effect of Goji (Lycium barbarum) on expression of genes related to cell survival.
AB  - This study investigated the interrelationship between Lycium barbarum (goji) and
      gene expression in mouse spleen. Oligomicroarray technology was employed to
      explore the comprehensive response of gene expression and to screen candidate
      marker genes in the spleens of mice fed a goji suspension. Goji was micronized by
      media milling and then used to evaluate the effect of size reduction. The average
      diameter of nano/submicrometer goji was about 100 nm, which exhibited no
      cytotoxicity to cell lines IEC-6 (rat normal small intestinal cell line) and Caco
      2 (human colon adenocarcinoma cell line). It was found that three genes, TNF,
      Nfkb1, and Bcl-2, were up-regulated and two genes, APAF-1 and caspase-3, were
      down-regulated by goji. This phenomenon could be helpful for cytoprotection when
      cells undergo stress or damage that induces the apoptotic pathway. Size reduction
      into nano/submicrometer scale enhanced bioactivity.

PMID- 21846087
TI  - Shell cross-linked micelle-based nanoreactors for the substrate-selective
      hydrolytic kinetic resolution of epoxides.
AB  - Shell cross-linked micelles (SCMs) containing Co(III)-salen cores were prepared
      from amphiphilic poly(2-oxazoline) triblock copolymers. The catalytic activity of
      these nanoreactors for the hydrolytic kinetic resolution of various terminal
      epoxides was investigated. The SCM catalysts showed high catalytic efficiency
      and, more significantly, substrate selectivity based on the hydrophobic nature of
      the epoxide. Moreover, because of the nanoscale particle size and the high
      stability, the catalyst could be recovered easily by ultrafiltration and reused
      with high activity for eight cycles.

PMID- 21846088
TI  - Simulating picosecond iron K-edge X-ray absorption spectra by ab initio methods
      to study photoinduced changes in the electronic structure of Fe(II) spin
      crossover complexes.
AB  - Recent time-resolved X-ray absorption experiments probing the low-spin to high
      spin photoconversion in Fe(II) complexes have monitored the complex interplay
      between electronic and structural degrees of freedom on an ultrafast time scale.
      In this study, we use transition potential (TP) and time-dependent (TD) DFT to
      simulate the picosecond time-resolved iron K-edge X-ray absorption spectrum of
      the spin crossover (SCO) complex, [Fe(tren(py)(3))](2+). This is achieved by
      simulating the X-ray absorption spectrum of [Fe(tren(py)(3))](2+) in its low-spin
      (LS), (1)A(1), ground state and its high-spin (HS), (5)T(2), excited state. These
      results are compared with the X-ray absorption spectrum of the high-spin analogue
      (HSA), [Fe(tren(6-Me-py)(3))](2+), which has a (5)T(2) ground state. We show that
      the TP-DFT methodology can simulate a 40 eV range of the iron K-edge XANES
      spectrum reproducing all of the major features observed in the static and
      transient spectra of the LS, HS, and HSA complexes. The pre-edge region of the K
      edge spectrum, simulated by TD-DFT, is shown to be highly sensitive to metal
      ligand bonding. Changes in the intensity of the pre-edge region are shown to be
      sensitive to both symmetry and pi-backbonding by analysis of relative electric
      dipole and quadrupole contributions to the transition moments. We generate a
      spectroscopic map of the iron 3d orbitals from our TD-DFT results and determine
      ligand field splitting energies of 1.55 and 1.35 eV for the HS and HSA complexes,
      respectively. We investigate the use of different functionals finding that hybrid
      functionals (such as PBE0) produce the best results. Finally, we provide a
      detailed comparison of our results with theoretical methods that have been
      previously used to interpret Fe K-edge spectroscopy of equilibrium and time
      resolved SCO complexes.

PMID- 21846089
TI  - Anti-inflammatory endiandric acid analogues from the roots of Beilschmiedia
      tsangii.
AB  - Bioassay-guided fractionation of roots of Beilschmiedia tsangii led to the
      isolation of six new endiandric acid analogues: tsangibeilin A (1), tsangibeilin
      B (2), endiandramide A (3), endiandric acid K (4), endiandric acid L (5), and
      endiandramide B (6). Also isolated were two new lignans, beilschminol A (7) and
      tsangin C (8), and six known compounds. The structures of 1-8 were determined by
      spectroscopic techniques. Compounds 3 and 6 exhibited potent iNOS inhibitory
      activity, with IC(50) values of 9.59 and 16.40 MUM, respectively.

PMID- 21846090
TI  - Evolution of ordering in iron oxide nanoparticle monolayers using electrophoretic
      deposition.
AB  - Iron-oxide nanoparticle monolayers and multilayers were assembled using dc
      electrophoretic deposition. The rate of deposition and the total particle
      deposition were controlled by varying the concentration of nanoparticles and the
      deposition time, respectively. Using scanning electron microscopy, we performed a
      time-resolved study that demonstrated the growth of the monolayer from a single
      isolated nanoparticle to a nearly complete layer. We observed tight, hexagonal
      packing of the nanoparticles indicating strong particle-particle interaction.
      Multilayer growth was assessed using scanning electron microscopy and atomic
      force microscopy, revealing a monolayer-by-monolayer growth process.

PMID- 21846091
TI  - Antimalarial beta-carbolines from the New Zealand ascidian Pseudodistoma opacum.
AB  - One tetrahydro-beta-carboline, (-)-7-bromohomotrypargine (1), and three
      alkylguanidine-substituted beta-carbolines, opacalines A, B, and C (2-4), have
      been isolated from the New Zealand ascidian Pseudodistoma opacum. The structures
      of the metabolites were determined by analysis of mass spectrometric and 2D NMR
      spectroscopic data. Natural products 2 and 3, synthetic debromo analogues 8 and
      9, and intermediate 16 exhibited moderate antimalarial activity toward a
      chloroquine-resistant strain of Plasmodium falciparum, with an IC50 range of 2.5
      14 MUM. The biosynthesis of 1-4 is proposed to proceed via a Pictet-Spengler
      condensation of 6-bromotryptamine and the alpha-keto acid transamination product
      of either arginine or homoarginine. Cell separation and 1H NMR analysis of P.
      opacum identified tetrahydro-beta-carboline 1 to be principally located in the
      zooids, while fully aromatized analogues 2-4 were localized to the test.

PMID- 21846092
TI  - Synthesis, structure, negative thermal expansion, and photocatalytic property of
      Mo doped ZrV2O7.
AB  - A new series of compounds identified in the phase diagram of ZrO(2)-V(2)O(5)
      MoO(3) have been synthesized via the solution combustion method. Single crystals
      of one of the compounds in the series, ZrV(1.50)Mo(0.50)O(7.25), were grown by
      the melt-cool technique from the starting materials with double the MoO(3)
      quantity. The room temperature average crystal structure of the grown crystals
      was solved using the single crystal X-ray diffraction technique. The crystals
      belong to the cubic crystal system, space group Pa3 (No. 205) with a = 8.8969 (4)
      A, V = 704.24 (6) A(3), and Z = 4. The final R(1) value of 0.0213 was achieved
      for 288 independent reflections during the structure refinement. The Zr(4+)
      occupies the special position (4a) whereas V(5+) and Mo(6+) occupy two unique
      (8c) Wyckoff positions. Two fully occupied O atoms, (24d) and (4b), one partially
      occupied O atom (8c) have been identified for this molybdovanadate, which is a
      unique feature for these crystals. The structure is related to both ZrV(2)O(7)
      and cubic ZrMo(2)O(8). The temperature dependent single crystal studies show
      negative thermal expansion above 370 K. The compounds have been characterized by
      powder X-ray diffraction, solid-state UV-vis diffuse reflectance spectra,
      scanning electron microscopy (SEM), and transmission electron microscopy (TEM).
      The photocatalytic activity of these compounds has been investigated for the
      degradation of various dyes, and these compounds show specificity toward the
      degradation of non-azoic dyes.

PMID- 21846093
TI  - Multifunctional magnetic materials obtained by insertion of spin-crossover
      Fe(III) complexes into chiral 3D bimetallic oxalate-based ferromagnets.
AB  - The syntheses, structures, and magnetic properties of compounds of formula
      [Fe(III)(5-Clsal(2)-trien)][Mn(II)Cr(III)(ox)(3)].0.5(CH(3)NO(2)) (1), [Fe(III)(5
      Brsal(2)-trien)][Mn(II)Cr(III)(ox)(3)] (2), and [In(III)(5-Clsal(2)
      trien)][Mn(II)Cr(III)(ox)(3)] (3) are reported. The structure of the three
      compounds, which crystallize in the orthorhombic P2(1)2(1)2(1) chiral space
      group, presents a 3D chiral anionic network formed by Mn(II) and Cr(III) ions
      linked through oxalate ligands with inserted [Fe(III)(5-Clsal(2)-trien)](+),
      [Fe(III)(5-Brsal(2)-trien)](+), and [In(III)(5-Clsal(2)-trien)](+) cations. The
      magnetic properties indicate that the three compounds undergo long-range
      ferromagnetic ordering at ca. 5 K. On the other hand, the inserted Fe(III)
      cations undergo a partial spin crossover in the case of 1 and 2.

PMID- 21846094
TI  - Cucurbit[8]uril rotaxanes.
AB  - The synthesis of [2]rotaxanes, each comprising a viologen core threaded through a
      cucurbit[8]uril (Q8, Figure 1) macrocycle and stoppered by tetraphenylmethane
      groups, and their binding to second guests as inclusion complexes in organic and
      aqueous media are described. Stoppering was observed to have little effect on
      binding. Chemical modification of the threaded guest was used to control
      solubility and binding characteristics, thus demonstrating a novel approach to
      making artificial receptors with readily modifiable properties.

PMID- 21846095
TI  - Formation of bimetallic Au-Pd and Au-Pt nanoparticles under hydrothermal
      conditions and microwave irradiation.
AB  - The reduction of chlorocomplexes of gold(III) from muriatic solutions by
      nanocrystal powders of palladium and platinum at 110 and 130  degrees C under
      hydrothermal conditions and the action of microwave irradiation has been
      investigated. The structure and composition of the solid phase have been
      characterized by transmission electron microscopy, X-ray diffraction, X-ray
      photoelectron spectroscopy, and chemical methods. Bimetallic particles with a
      core-shell structure have been revealed. The obtained particles are established
      to have a core of the metal reductant covered with a substitutional solid (Au,
      Pd) solution in case of palladium, and isolated by a gold layer in the case of
      platinum. The main reason for such a difference is the ratio between the rates of
      aggregation and reduction. It has been shown by the example of the Au-Pd system
      that the use of microwave irradiation allows us not only to accelerate the
      synthesis of particles but also to obtain more homogeneous materials in
      comparison with conventional heating.

PMID- 21846096
TI  - Structure-activity relationships in tripodal transmembrane anion transporters:
      the effect of fluorination.
AB  - A series of easy-to-make fluorinated tripodal anion transporters containing urea
      and thiourea groups have been prepared and their anion transport properties
      studied. Vesicle anion transport assays using ion-selective electrodes show that
      this class of compound is capable of transporting chloride through a lipid
      bilayer via a variety of mechanisms, including chloride/H(+) cotransport and
      chloride/nitrate, chloride/bicarbonate, and to a lesser extent an unusual
      chloride/sulfate antiport process. Calculations indicate that increasing the
      degree of fluorination of the tripodal transmembrane transporters increases the
      lipophilicity of the transporter and this is shown to be the major contributing
      factor in the superior transport activity of the fluorinated compounds, with a
      maximum transport rate achieved for clog P = 8. The most active transporter 5
      contained a urea functionality appended with a 3,5-bis(trifluoromethyl)phenyl
      group and was able to mediate transmembrane chloride transport at receptor to
      lipid ratios as low as 1:250000. Proton NMR titration and single crystal X-ray
      diffraction revealed the ability of the tripodal receptors to bind different
      anions with varying affinities in a 1:1 or 2:1 stoichiometry in solution and in
      the solid state. We also provide evidence that the most potent anion transporters
      are able to induce apoptosis in human cancer cells by using a selection of in
      vitro viability and fluorescence assays.

PMID- 21846097
TI  - Rapid determination of ractopamine in swine urine using surface-enhanced Raman
      spectroscopy.
AB  - Ractopamine is approved for use in swine to improve carcass leanness in the
      United States, but banned in the European Union and China because ractopamine
      residue may pose health risks. This study investigated the possibility of
      applying surface-enhanced Raman spectroscopy (SERS) for analysis of ractopamine
      in swine urine. Ractopamine (0.1-10 MUg mL(-1)) was added to urine samples
      collected from 20 swine to prepare a total of 240 samples. A simple
      centrifugation, a liquid-liquid extraction (LLE) method, and a more complicated
      method involving liquid-liquid extraction and solid-phase extraction (LLE-SPE)
      were used to extract ractopamine from urine samples. Principal component analysis
      (PCA) and partial least-squares (PLS) regression were used for spectral data
      analyses. Although no satisfactory result was obtained with the centrifugation
      method, ractopamine could be detected at levels of 0.8 and 0.4 MUg mL(-1) with
      the LLE and LLE-SPE extraction methods, respectively. The R2 of the PLS model of
      actual ractopamine values versus predicted values was 0.74 for the LLE method and
      0.73 for the LLE-SPE method. The SERS method with simple sample preparation has
      great potential for rapid analysis of ractopamine in swine urine.

PMID- 21846098
TI  - Stabilization of alkaline phosphatase with Au@Ag2O nanoparticles.
AB  - Here, we report that a conductive Au@Ag(2)O nanoparticle structure significantly
      enhances the stability of alkaline phosphatase (AlkP) in the presence of the
      inhibitors urea and l-phenylalanine (Phe). The enzyme/nanoparticle construct is
      prepared by associating the enzyme with citrate-capped Au particles, and then
      adding Ag(+). UV-vis and XPS spectroscopy and transmission electron microscopy
      confirm the core@shell structure. AlkP activity was quantified in the presence
      and absence of the two inhibitors using a time-resolved colorimetric assay. The
      results indicate that 21% of the initial active AlkP is incorporated into the
      nanoparticle structure. More importantly, however, the Au@Ag(2)O core@shell host
      reduces the inhibitory effect of urea and Phe by factors ranging from 3 to 12,
      depending on the inhibitor and its concentration, compared to the wild-type
      enzyme.

PMID- 21846100
TI  - Chiral conversion and memory of TPPS J-aggregates in complex micelles: PEG-b
      PDMAEMA/TPPS.
AB  - In the presence of tryptophan (Trp), complex micelles were prepared by 5,10,15,20
      tetrakis(4-sulfonatophenyl) porphyrin (TPPS) and poly(ethylene glycol)-block
      poly(2-(dimethylamino)ethyl methylacrylate) (PEG-b-PDMAEMA) in aqueous solutions
      at pH 1.8. Different mixing sequences led to different morphologies. Spheres and
      nanorods of small size were obtained in sequence I (P/Trp+TPPS) where TPPS was
      added into the mixed solution of PEG-b-PDMAEMA and Trp. More nanorods of larger
      length were achieved in sequence II (TPPS/Trp+P) where the copolymer was added as
      the last component. Two types of supramolecular chirality of TPPS aggregates
      caused by mixing sequences were investigated. In (P/Trp+TPPS), the circular
      dichroism (CD) signal of H-band was in line with the chirality of Trp while that
      of J-band exhibited an opposite signal (Chirality I). In (TPPS/Trp+P), chiral
      signals at both H- and J-bands followed that of Trp (Chirality II). The
      conversion between the two types of chirality can be accomplished by modulating
      the molar ratio of the repeating units on block PDMAEMA to TPPS, or a cycle of pH
      1.8-5.5-1.8 processing on the micelle solution. In addition, the supramolecular
      chirality can be memorized via strong electrostatic interaction with achiral
      copolymer even after removal of the chiral template, but only Chirality II can be
      cyclically "switched-off-on".

PMID- 21846099
TI  - Orosensory stimulation effects on human saliva proteome.
AB  - Saliva flow induced by 6-gingerol (pungent), hydroxy-alpha/beta-sanshools
      (tingling), and citric acid (sour) was measured, and the time-dependent changes
      in the whole saliva proteome were analyzed by means of 2D-PAGE, followed by
      tryptic in-gel digestion and MALDI-TOF-MS peptide mass fingerprint analysis. The
      proteins showing significantly decreased abundance after oral 6-gingerol
      stimulation were identified as glutathione S-transferase P, the heat shock
      protein beta-1, the heat shock 70 kDa protein 1, annexin A1, and cytoplasmic beta
      actin, whereas prolactin inducible proteins (PIP), short palate, lung and nasal
      epithelium carcinoma-associated protein 2 (SPLUNC2), zinc-alpha-2-glycoproteins
      (Zn-alpha-GP), and carbonic anhydrase VI (CAVI) were found with increased
      abundance. As the effects of this study were observed instantaneously upon
      stimulation, any proteome modulation is very likely to result from the release of
      proteins from preformed vesicles and not from de novo synthesis. The elevated
      levels of SPLUNC2, Zn-alpha-GP, and CAVI might be interpreted to trigger innate
      protective mechanisms in mucosal immunity and in nonimmune mucosal defense and
      might play an important role during the initial stage of inflammation.

PMID- 21846101
TI  - Three dimensional models of Cu(2+)-Abeta(1-16) complexes from computational
      approaches.
AB  - Elucidation of the coordination of metal ions to Abeta is essential to understand
      their role in its aggregation and to rationally design new chelators with
      potential therapeutic applications in Alzheimer disease. Because of that, in the
      last 10 years several studies have focused their attention in determining the
      coordination properties of Cu(2+) interacting with Abeta. However, more important
      than characterizing the first coordination sphere of the metal is the
      determination of the whole Cu(2+)-Abeta structure. In this study, we combine
      homology modeling (HM) techniques with quantum mechanics based approaches (QM) to
      determine plausible three-dimensional models for Cu(2+)-Abeta(1-16) with three
      histidines in their coordination sphere. We considered both epsilon and delta
      coordination of histidines 6, 13, and 14 as well as the coordination of different
      possible candidates containing oxygen as fourth ligand (Asp1, Glu3, Asp7, Glu11,
      and CO(Ala2)). Among the 32 models that enclose COO(-), the lowest energy
      structures correspond to [O(E3),N(delta)(H6),N(epsilon)(H13),N(epsilon)(H14)]
      (1), [O(E3),N(delta)(H6),N(delta)(H13),N(delta)(H14)] (2), and
      [O(D7),N(epsilon)(H6),N(delta)(H13),N(delta)(H14)] (3). The most stable model
      containing CO(Ala2) as fourth ligand in the Cu(2+) coordination sphere is
      [O(c)(A2),N(epsilon)(H6),N(delta)(H13),N(epsilon)(H14)] (4). An estimation of the
      relative stability between Glu3 (1) and CO(Ala2) (4) coordinated complexes seems
      to indicate that the preference for the latter coordination may be due to solvent
      effects. The present results also show the relationship between the peptidic and
      metallic moieties in defining the overall geometry of the complex and illustrate
      that the final stability of the complexes results from a balance between the
      metal coordination site and amyloid folding upon complexation.

PMID- 21846102
TI  - Contribution of telomere G-quadruplex stabilization to the inhibition of
      telomerase-mediated telomere extension by chemical ligands.
AB  - Inhibition of telomerase activity through stabilizing telomere G-quadruplex with
      small chemical ligands is emerging as a novel strategy for cancer therapy. For
      the large number of ligands that have been reported to inhibit telomerase
      activity, it is difficult to validate the contribution of G-quadruplex
      stabilization to the overall inhibition. Using a modified telomere repeat
      amplification protocol (TRAP) method to differentiate the telomere G-quadruplex
      independent effect from dependent ones, we analyzed several ligands that have
      high affinity and/or selectivity to telomere G-quadruplex. Our results show that
      these ligands effectively inhibited telomerase activity in the absence of
      telomere G-quadruplex. The expected G-quadruplex-dependent inhibition was only
      obvious for the cationic ligands at low K(+) concentration, but it dramatically
      decreased at physiological concentration of K(+). These observations demonstrate
      that the ligands are much more than G-quadruplex stabilizers with a strong G
      quadruplex-irrelevant off-target effect. They inhibit telomerase via multiple
      pathways in which stabilization of telomere G-quadruplex may only make a minor or
      neglectable contribution under physiologically relevant conditions depending on
      the stability of telomere G-quadruplex under ligand-free conditions.

PMID- 21846103
TI  - Quantitative characterization of temperature-independent and temperature
      dependent protein-protein interactions in highly nonideal solutions.
AB  - The interaction among each of three dilute "tracer" proteins (bovine serum
      albumin, superoxide dismutase, and ovomucoid) at a concentration of 2 mg/mL and
      each of two "crowder" proteins (ovomucoid and BSA) at concentrations up to 100
      mg/mL was characterized by analysis of dependence of the equilibrium gradients of
      both tracer and crowder upon the concentration of crowder. The equilibrium
      gradients of both crowder proteins were found to be independent of temperature
      over the range 5-37  degrees C. The equilibrium gradients of tracer BSA and
      ovomucoid in the complementary crowder species were likewise found to be
      independent of temperature over this range, indicating that interaction among
      these tracers and crowders is predominantly repulsive and essentially entirely
      entropic in nature. The equilibrium gradient of tracer SOD in BSA was also found
      to be independent of temperature over this range, but the gradient of tracer SOD
      in ovomucoid depended significantly upon temperature in a manner indicating a
      significant enthalpic (attractive) component of the overall interaction between
      SOD and ovomucoid. The experimental data are analyzed using model-free expansions
      of the thermodynamic activity coefficients of tracer and crowder in powers of the
      concentration of crowder and using approximate statistical thermodynamic models
      based upon highly simplified descriptions of molecular structure and
      interactions. Detailed analysis of the results indicates a relatively small
      contribution of nonspecific attraction to the total protein-protein interaction,
      which is dominated by steric repulsion.

PMID- 21846104
TI  - Changes in water-soluble vitamins and antioxidant capacity of fruit juice-milk
      beverages as affected by high-intensity pulsed electric fields (HIPEF) or heat
      during chilled storage.
AB  - The effect of high-intensity pulsed electric fields (HIPEF) or thermal processes
      and refrigerated storage on water-soluble vitamins and antioxidant capacity of
      beverages containing fruit juices and whole (FJ-WM) or skim milk (FJ-SM) was
      assessed. Peroxidase (POD) and lipoxygenase (LOX) inactivation as well as color
      changes were also studied. High vitamin C retention was observed in HIPEF and
      thermally treated beverages, but a significant depletion of the vitamin during
      storage occurred, which was correlated with antioxidant capacity. HIPEF treatment
      did not affect the concentration of group B vitamins, which also remained
      constant over time, but thermally treated beverages showed lower riboflavin
      (vitamin B2) concentration. With regard to enzyme activity, thermal processing
      was more effective than HIPEF on POD and LOX inactivation. The color of the
      beverages was maintained after HIPEF processing and during storage. Consequently,
      HIPEF processing could be a feasible technology to attain beverages with fruit
      juices and milk with high vitamin content and antioxidant potential.

PMID- 21846105
TI  - Direct and reliable patterning of plasmonic nanostructures with sub-10-nm gaps.
AB  - Nanoscale gaps in metal films enable strong field enhancements in plasmonic
      structures. However, the reliable fabrication of ultrasmall gaps (<10 nm) for
      real applications is still challenging. In this work, we report a method to
      directly and reliably fabricate sub-10-nm gaps in plasmonic structures without
      restrictions on pattern design. This method is based on a lift-off process using
      high-resolution electron-beam lithography with a negative-tone hydrogen
      silsesquioxane (HSQ) resist, where the resulting nanogap size is determined by
      the width of the patterned HSQ structure, which could be written at less than 10
      nm. With this method, we fabricated densely packed gold nanostructures of varying
      geometries separated by ultrasmall gaps. By controlling structure sizes during
      lithography with nanometer precision, the plasmon resonances of the resulting
      patterns could be accurately tuned. Optical and surface-enhanced Raman scattering
      (SERS) measurements on the patterned structures show that this technique has
      promising applications in the fabrication of passively tunable plasmonic
      nanostructures with ultrasmall gaps.

PMID- 21846106
TI  - Ecotoxicological effects of activated carbon amendments on macroinvertebrates in
      nonpolluted and polluted sediments.
AB  - Amendment of contaminated sediment with activated carbon (AC) is a remediation
      technique that has demonstrated its ability to reduce aqueous concentrations of
      hydrophobic organic compounds. The application of AC, however, requires
      information on possible ecological effects, especially effects on benthic
      species. Here, we provide data on the effects of AC addition on locomotion,
      ventilation, sediment avoidance, mortality, and growth of two benthic species, 
      Gammarus pulex  and  Asellus aquaticus , in clean versus polycyclic aromatic
      hydrocarbon (PAH) contaminated sediment. Exposure to PAH was quantified using 76
      MUm polyoxymethylene passive samplers. In clean sediment, AC amendment caused no
      behavioral effects on both species after 3-5 days exposure, no effect on the
      survival of  A. aquaticus , moderate effect on the survival of  G. pulex  (LC(50)
      = 3.1% AC), and no effects on growth. In contrast, no survivors were detected in
      PAH contaminated sediment without AC. Addition of 1% AC, however, resulted in a
      substantial reduction of water exposure concentration and increased survival of 
      G. pulex  and  A. aquaticus  by 30 and 100% in 8 days and 5 and 50% after 28 days
      exposure, respectively. We conclude that AC addition leads to substantial
      improvement of habitat quality in contaminated sediments and outweighs ecological
      side effects.

PMID- 21846108
TI  - Solution and microbial controls on the formation of reduced U(IV) species.
AB  - Reduction of U(VI) to U(IV) as the result of direct or indirect microbial
      activity is currently being explored for in situ remediation of subsurface U
      plumes, under the assumption that U(IV) solubility is controlled by the low
      solubility mineral uraninite (U(IV)-dioxide). However, recent characterizations
      of U in sediments from biostimulated field sites, as well as laboratory U(VI)
      bioreduction studies, report on the formation of U(IV) species that lack the
      U?O(2)?U coordination of uraninite, suggesting that phases other than uraninite
      may be controlling U(IV) solubility in environments with complexing surfaces and
      ligands. To determine the controls on the formation of such nonuraninite U(IV)
      species, the current work studied the reduction of carbonate-complexed U(VI) by
      (1) five Gram-positive  Desulfitobacterium  strains, (2) the Gram-negative
      bacteria  Anaeromyxobacter dehalogenans  2CP-C and  Shewanella putrefaciens 
      CN32, and (3) chemically reduced 9,10-anthrahydroquinone-2,6-disulfonate
      (AH(2)QDS, a soluble reductant). Further, the effects of 0.3 mM dissolved
      phosphate on U(IV) species formation were explored. Extended X-ray absorption
      fine structure (EXAFS) spectroscopy analysis demonstrated that the addition of
      phosphate causes the formation of a nonuraninite, phosphate-complexed U(IV)
      species, independent of the biological or abiotic mode of U(VI) reduction. In
      phosphate-free medium, U(VI) reduction by  Desulfitobacterium  spp. and by
      AH(2)QDS resulted in nonuraninite, carbonate-complexed U(IV) species, whereas
      reduction by  Anaeromyxobacter  or  Shewanella  yielded nanoparticulate
      uraninite. These findings suggest that the Gram-positive  Desulfitobacterium 
      strains and the Gram-negative  Anaeromyxobacter  and  Shewanella  species use
      distinct mechanisms to reduce U(VI).

PMID- 21846109
TI  - Synthesis and structure-activity relationships of varied ether linker analogues
      of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7
      dihydro-5h-imidazo[2,1-b][1,3]oxazine (PA-824).
AB  - New analogues of antitubercular drug PA-824 were synthesized, featuring
      alternative side chain ether linkers of varying size and flexibility, seeking
      drug candidates with enhanced metabolic stability and high efficacy. Both alpha
      methyl substitution and removal of the benzylic methylene were broadly tolerated
      in vitro, with a biaryl example of the latter class exhibiting an 8-fold better
      efficacy than the parent drug in a mouse model of acute  Mycobacterium
      tuberculosis  infection and negligible fragmentation to an alcohol metabolite in
      liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and
      pentynyloxy) provided greater potencies against replicating  M. tb  (monoaryl
      analogues), with propynyl ethers being most effective under anaerobic
      (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and
      biaryl derivatives, aerobic activity was maximal with the original (OCH(2))
      linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than
      the parent drug in the acute model, and it was slightly superior to
      antitubercular drug OPC-67683 in a chronic infection model.

PMID- 21846107
TI  - Gold nanoparticles: a revival in precious metal administration to patients.
AB  - Gold has been used as a therapeutic agent to treat a wide variety of rheumatic
      diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus
      erythematosus. Although the use of gold has been largely superseded by newer
      drugs, gold nanoparticles are being used effectively in laboratory based clinical
      diagnostic methods while concurrently showing great promise in vivo either as a
      diagnostic imaging agent or a therapeutic agent. For these reasons, gold
      nanoparticles are therefore well placed to enter mainstream clinical practice in
      the near future. Hence, the present review summarizes the chemistry,
      pharmacokinetics, biodistribution, metabolism, and toxicity of bulk gold in
      humans based on decades of clinical observation and experiments in which gold was
      used to treat patients with rheumatoid arthritis. The beneficial attributes of
      gold nanoparticles, such as their ease of synthesis, functionalization, and shape
      control are also highlighted demonstrating why gold nanoparticles are an
      attractive target for further development and optimization. The importance of
      controlling the size and shape of gold nanoparticles to minimize any potential
      toxic side effects is also discussed.

PMID- 21846110
TI  - Block versus random amphiphilic copolymers as antibacterial agents.
AB  - We examined the antibacterial and hemolytic activities in a series of amphiphilic
      block and random copolymers of poly(vinyl ether) derivatives prepared by base
      assisting living cationic polymerization. Block and random amphiphilic copolymers
      with similar monomer compositions showed the same level of activity against 
      Escherichia coli . However, the block copolymers are much less hemolytic compared
      to the highly hemolytic random copolymers. These results indicate that the
      amphiphilic copolymer structure is a key determinant of activity. Furthermore,
      the block copolymers induced dye leakage from lipid vesicles consisting of  E.
      coli -type lipids, but not mammalian lipids, while the random copolymers
      disrupted both types of vesicles. In addition, both copolymers displayed
      bactericidal and hemolytic activities at concentrations 1 or 2 orders of
      magnitude lower than their critical (intermolecular) aggregation concentrations
      (CACs), as determined by light scattering measurements. This suggests that
      polymer aggregation or macromolecular assembly is not a requisite for the
      antibacterial activity and selectivity against bacteria over human red blood
      cells (RBCs). We speculate that different single-chain conformations between the
      block and random copolymers play an important role in the antibacterial action
      and underlying antibacterial mechanisms.

PMID- 21846111
TI  - Mono- and dinitrosyls on copper(I) site in a zeolite model: effects of static
      correlation.
AB  - Multiconfigurational RASSCF/RASPT2 approach has been applied to investigate
      bonding of one and two nitric oxide (NO) molecules to a simple model of Cu(I)
      site in zeolite environment, Cu(I)[Al(OH)(4)]. Two binding modes were considered
      for the mononitrosyls and four alternative structures for the dinitrosyls (each
      one in either singlet or triplet state). Stabilities of the mono- and dinitrosyl
      complexes obtained from the multireference calculations were compared to the
      previously reported coupled cluster CCSD(T) results, as well as to DFT
      calculations performed here with various functionals, either hybrid or nonhybrid
      ones. RASSCF calculations provided also a qualitative insight into the electronic
      structure of the studied complexes, concerning mainly the interaction between the
      Cu and the NO ligand, and between the two NO fragments. Whereas the electronic
      structure of the mononitrosyls is dominated by a single configuration, the
      dinitrosyls have a considerably multireference character. Various effects of
      nondynamical correlation have been pointed out for these interesting species,
      trying to assess their impact on performance of the tested DFT methods.

PMID- 21846112
TI  - Assessing the effectiveness of thin-layer sand caps for contaminated sediment
      management through passive sampling.
AB  - The effectiveness of thin-layer sand capping for contaminated sediment management
      (capping with a layer of thickness comparable to the depth of benthic
      interactions) is explored through experiments with laboratory-scale microcosms
      populated with the deposit-feeding oligochaete, Ilyodilus templetoni. Passive
      sampling of pore water concentrations in the microcosms using
      polydimethylsiloxane (PDMS)-coated fibers enabled quantification of high
      resolution vertical concentration profiles that were used to infer contaminant
      migration rates and mechanisms. Observed concentration profiles were consistent
      with models that combine traditional contaminant transport processes (sorption
      retarded diffusion) with bioturbation. Predictions of bioaccumulation based on
      contaminant pore water concentrations within the surface layer of the cap
      correlated well with observed bioaccumulation (correlation coefficient of 0.92).
      The results of this study show that thin-layer sand caps of contaminated
      sediments can be effective at reducing the bioaccumulation of polycyclic aromatic
      hydrocarbons (PAHs) provided the thickness of the cap layer exceeds the depth of
      organism interaction with the sediments and the pore water concentrations within
      the biologically active zone remain low (e.g., when molecular diffusion controls
      transport from the underlying sediment layer).

PMID- 21846113
TI  - In situ carboxyl activation using a silatropic switch: a new approach to amide
      and peptide constructions.
AB  - The novel reactivity of O-silylthionoesters with amine nucleophiles to generate
      oxoamides (rather than thioamides) is described. A straightforward first
      generation trimethylsilylation protocol using bistrimethylsilylacetamide (BSA)
      combined with the unique reactivity of the O-silylthionoesters toward 1 degrees 
      and 2 degrees  amines to generate oxoamides provides the simplest means of
      activating a thiol acid for peptide bond formation at neutral pH. Excellent
      stereoretention is observed.

PMID- 21846115
TI  - Deciphering the protective role of nitric oxide against salt stress at the
      physiological and proteomic levels in maize.
AB  - Saline stress is a major factor that limits crop yield. Nitric oxide (NO) is
      functional during plant growth, development, and defense responses. In the
      present study, the protective role of NO in alleviating saline stress in maize at
      the physiological and proteomic levels was examined. Our results showed that salt
      treatment quickly induced NO accumulation and addition of the NO donor S-nitroso
      N-acetylpenicillamine (SNAP) efficiently eliminated the inhibitory effect of salt
      on shoot growth and photosynthesis and inhibited salt-inducible H2O2
      accumulation. These effects could be reversed by NO metabolic scavengers and
      inhibitors. Further proteomic and Western blotting analysis revealed that NO
      induced G-protein-associated protein accumulation and antioxidant enzymes
      activities, in addition to activation of defense proteins, energy metabolism, and
      cell structure/division in salt-treated maize seedlings. Controlling the G
      protein status with G-protein activators or inhibitors also affected NO
      generation and root and stem growth in maize seedlings after saline stress. On
      the basis of these results, we propose that NO enhances salt tolerance in maize
      seedlings by enhancing antioxidant enzyme activities and controlling H2O2 levels,
      and these effects are accompanied by diverse downstream defense responses. During
      this process, G-protein signaling is an early event that works upstream of NO
      biogenesis.

PMID- 21846116
TI  - Size- and temperature-dependent charge transport in PbSe nanocrystal thin films.
AB  - We report the size- and temperature-dependence of electron transport in thin
      films of PbSe nanocrystals. Upon increasing temperature over the range 28-200 K,
      the electron transport underwent a transition in mechanism from Efros-Shklovskii
      variable-range-hopping (ES-VRH) to nearest-neighbor-hopping (NNH). The transition
      occurred at higher temperatures for films with smaller particles. The electron
      localization length, estimated from the ES-VRH model, was comparable to the
      nanocrystal size and scaled systematically with nanocrystal diameter. The
      activation energy from the NNH regime was also size-dependent, which is
      attributed both to size-dependent Coulomb effects and the size-distribution of
      nanocrystals.

PMID- 21846117
TI  - Uncertainty in life cycle greenhouse gas emissions from United States natural gas
      end-uses and its effects on policy.
AB  - Increasing concerns about greenhouse gas (GHG) emissions in the United States
      have spurred interest in alternate low carbon fuel sources, such as natural gas.
      Life cycle assessment (LCA) methods can be used to estimate potential emissions
      reductions through the use of such fuels. Some recent policies have used the
      results of LCAs to encourage the use of low carbon fuels to meet future energy
      demands in the U.S., without, however, acknowledging and addressing the
      uncertainty and variability prevalent in LCA. Natural gas is a particularly
      interesting fuel since it can be used to meet various energy demands, for
      example, as a transportation fuel or in power generation. Estimating the
      magnitudes and likelihoods of achieving emissions reductions from competing end
      uses of natural gas using LCA offers one way to examine optimal strategies of
      natural gas resource allocation, given that its availability is likely to be
      limited in the future.  In this study, the uncertainty in life cycle GHG
      emissions of natural gas (domestic and imported) consumed in the U.S. was
      estimated using probabilistic modeling methods. Monte Carlo simulations are
      performed to obtain sample distributions representing life cycle GHG emissions
      from the use of 1 MJ of domestic natural gas and imported LNG. Life cycle GHG
      emissions per energy unit of average natural gas consumed in the U.S were found
      to range between -8 and 9% of the mean value of 66 g CO(2)e/MJ. The probabilities
      of achieving emissions reductions by using natural gas for transportation and
      power generation, as a substitute for incumbent fuels such as gasoline, diesel,
      and coal were estimated. The use of natural gas for power generation instead of
      coal was found to have the highest and most likely emissions reductions (almost a
      100% probability of achieving reductions of 60 g CO(2)e/MJ of natural gas used),
      while there is a 10-35% probability of the emissions from natural gas being
      higher than the incumbent if it were used as a transportation fuel. This
      likelihood of an increase in GHG emissions is indicative of the potential failure
      of a climate policy targeting reductions in GHG emissions.

PMID- 21846118
TI  - Halogenated 2'-benzoylpyridine thiosemicarbazone (XBpT) chelators with potent and
      selective anti-neoplastic activity: relationship to intracellular redox activity.
AB  - Iron chelators of the 2'-benzoylpyridine thiosemicarbazone (BpT) class show
      substantial potential as anticancer agents. To explore structure-activity
      relationships, new BpT analogues were designed that incorporated halogen
      substituents on the noncoordinating phenyl group (XBpTs). These XBpT ligands
      exhibited potent antiproliferative activity with some analogues exceeding that of
      the parent BpT compound. Importantly, there was an appreciable therapeutic index
      in vitro, as mortal cells were significantly less affected by these chelators
      relative to neoplastic cells. The addition of a halogen led to a halogen-specific
      increase in the redox potential of XBpT-Fe complexes. Probing for chelator
      induced intracellular reactive oxygen species (ROS) with the fluorescent probe,
      2',7'-dichlorofluorescein, revealed a 1.5-4.7-fold increase in fluorescence upon
      incorporation of Cl, Br, or I to the parent analogues. Furthermore, an important
      structure-activity relationship was deduced where the addition of halogens led to
      a positive correlation between intracellular ROS generation and antiproliferative
      activity in the more hydrophilic BpT parent compounds.

PMID- 21846119
TI  - Promising fast energy transfer system via an easy synthesis: Bodipy-porphyrin
      dyads connected via a cyanuric chloride bridge, their synthesis, and
      electrochemical and photophysical investigations.
AB  - The boron dipyrrin (Bodipy) chromophore was combined with either a free-base or a
      Zn porphyrin moiety (H(2)P and ZnP respectively), via an easy synthesis involving
      a cyanuric chloride bridging unit, yielding dyads Bodipy-H(2)P (4) and Bodipy-ZnP
      (5). The photophysical properties of Bodipy-H(2)P (4) and Bodipy-ZnP (5) were
      investigated by UV-Vis absorption and emission spectroscopy, cyclic voltammetry,
      and femtosecond transient absorption spectroscopy. The comparison of the
      absorption spectra and cyclic voltammograms of dyads Bodipy-H(2)P (4) and Bodipy
      ZnP (5) with those of their model compounds Bodipy, H(2)P, and ZnP shows that the
      spectroscopic and electrochemical properties of the constituent chromophores are
      essentially retained in the dyads indicating negligible interaction between them
      in the ground state. In addition, luminescence and transient absorption
      experiments show that excitation of the Bodipy unit in Bodipy-H(2)P (4) and
      Bodipy-ZnP (5) into its first singlet excited state results in rapid Bodipy to
      porphyrin energy transfer-k(4) = 2.9 * 10(10) s(-1) and k(5) = 2.2 * 10(10) s(-1)
      for Bodipy-H(2)P (4) and Bodipy-ZnP (5), respectively-generating the first
      porphyrin-based singlet excited state. The porphyrin-based singlet excited states
      give rise to fluorescence or undergo intersystem crossing to the corresponding
      triplet excited states. The title complexes could also be used as precursors for
      further substitution on the third chlorine atom on the cyanuric acid moiety.

PMID- 21846120
TI  - Enhanced performance of dye-sensitized solar cells by utilization of an external,
      bifunctional layer consisting of uniform beta-NaYF4:Er3+/Yb3+ nanoplatelets.
AB  - Uniform beta-NaYF(4):Er(3+)/Yb(3+) hexagonal nanoplatelets were synthesized via a
      modified hydrothermal route, and the nanoplatelets were applied as an external,
      bifunctional layer in a novel DSC configuration consisting of only one internal
      TiO(2) transparent layer. Approximately 10% enhancements of photocurrent and
      overall DSC efficiency are demonstrated by the addition of the external layer,
      which exhibits two functions of light reflecting and near-infrared (NIR) light
      harvesting. The novel DSC configuration not only simplifies the DSC fabrication
      process but also eliminates charge recombination induced by the conducting up
      converting nanocrystals when used internally thus opening the path for other more
      efficient up-converting nanocrystals to be designed and applied.

PMID- 21846121
TI  - Cocrystals of quercetin with improved solubility and oral bioavailability.
AB  - Flavonoids have been studied extensively due to the observation that diets rich
      in these compounds are associated with lower incidences of many diseases. One of
      the most studied flavonoids, quercetin, is also the most abundant of these
      compounds in the plant kingdom. Numerous therapeutic bioactivities have been
      identified in vitro. However, its in vivo efficacy in pure form is limited by
      poor bioavailability, primarily due to its low solubility and consequent low
      absorption in the gut. Cocrystallization has gained attention recently as a means
      for improving the physicochemical characteristics of a compound. Here, we
      synthesized and evaluated four new cocrystals of quercetin (QUE):
      quercetin:caffeine (QUECAF), quercetin:caffeine:methanol (QUECAF.MeOH),
      quercetin:isonicotinamide (QUEINM), and quercetin:theobromine dihydrate (QUETBR .
      2H(2)O). Each of these cocrystals exhibited pharmacokinetic properties that are
      vastly superior to those of quercetin alone. Cocrystallization was able to
      overcome the water insolubility of quercetin, with all four cocrystals exhibiting
      some degree of solubility. The QUECAF and QUECAF.MeOH cocrystals increased the
      solubility of QUE by 14- and 8-fold when compared to QUE dihydrate. We
      hypothesized that this improved solubility would translate into enhanced systemic
      absorption of QUE. This hypothesis was supported in our pharmacokinetic study.
      The cocrystals outperformed QUE dihydrate with increases in bioavailability up to
      nearly 10-fold.

PMID- 21846122
TI  - Detection of synthetic testosterone use by novel comprehensive two-dimensional
      gas chromatography combustion-isotope ratio mass spectrometry.
AB  - We report the first demonstration of comprehensive two-dimensional gas
      chromatography combustion-isotope ratio mass spectrometry (GC*GCC-IRMS) for the
      analysis of urinary steroids to detect illicit synthetic testosterone use, of
      interest in sport doping. GC coupled to IRMS (GCC-IRMS) is currently used to
      measure the carbon isotope ratios (CIRs, delta(13)C) of urinary steroids in
      antidoping efforts; however, extensive cleanup of urine extracts is required
      prior to analysis to enable baseline separation of target steroids. With its
      greater separation capabilities, GC*GC has the potential to reduce sample
      preparation requirements and enable CIR analysis of minimally processed urine
      extracts. Challenges addressed include online reactors with minimized dimensions
      to retain narrow peak shapes, baseline separation of peaks in some cases, and
      reconstruction of isotopic information from sliced steroid chromatographic peaks.
      Difficulties remaining include long-term robustness of online reactors and urine
      matrix effects that preclude baseline separation and isotopic analysis of low
      concentration and trace components. In this work, steroids were extracted,
      acetylated, and analyzed using a refined, home-built GC*GCC-IRMS system. 11
      Hydroxyandrosterone and 11-ketoetiocolanolone were chosen as endogenous reference
      compounds because of their satisfactory signal intensity, and their CIR was
      compared to target compounds androsterone and etiocholanolone. Separately, a
      GC*GC-quadrupole MS system was used to measure testosterone (T)/epitestosterone
      (EpiT) concentration ratios. Urinary extracts of urine pooled from professional
      athletes and urine from one individual that received testosterone gel (T-gel) and
      one individual that received testosterone injections (T-shots) were analyzed. The
      average precisions of delta(13)C and Deltadelta(13)C measurements were
      SD(delta(13)C) approximately +/-10/00 (n = 11). The T-shot sample resulted in a
      positive for T use with a T/EpiT ratio of >9 and CIR measurements of
      Deltadelta(13)C > 50/00, both fulfilling World Anti-Doping Agency criteria. These
      data show for the first time that synthetic steroid use is detectable by GC*GCC
      IRMS without the need for extensive urine cleanup.

PMID- 21846123
TI  - Use of catalytic fluoride under neutral conditions for cleaving silicon-oxygen
      bonds.
AB  - This Article describes the development of conditions for cleaving silicon-oxygen
      bonds using catalytic quantities of fluoride at neutral pH in mixed organic
      aqueous solutions that contain buffer. A variety of silicon protecting groups can
      be removed under these conditions, which show tolerance for acid- and base
      sensitive groups. A modified procedure also is presented using catalytic fluoride
      in anhydrous dimethyl sulfoxide-methanol, which generates primarily volatile
      silicon byproducts.

PMID- 21846124
TI  - Role of biofilms in sorptive removal of steroidal hormones and 4-nonylphenol
      compounds from streams.
AB  - Stream biofilms play an important role in geochemical processing of organic
      matter and nutrients, however, the significance of this matrix in sorbing trace
      organic contaminants is less understood. This study focused on the role of stream
      biofilms in sorbing steroidal hormones and 4-nonylphenol compounds from surface
      waters using biofilms colonized in situ on artificial substrata and subsequently
      transferred to the laboratory for controlled batch sorption experiments.
      Steroidal hormones and 4-nonylphenol compounds readily sorb to stream biofilms as
      indicated by organic matter partition coefficients (K(om), L kg(-1)) for 17beta
      estradiol (10(2.5-2.8) L kg(-1)), 17alpha-ethynylestradiol (10(2.5-2.9) L kg(
      1)), 4-nonylphenol (10(3.4-4.6) L kg(-1)), 4-nonylphenolmonoethoxylate (10(3.5
      4.0) L kg(-1)), and 4-nonylphenoldiethoxylate (10(3.9-4.3) L kg(-1)). Experiments
      using water quality differences to induce changes in the relative composition of
      periphyton and heterotrophic bacteria in the stream biofilm did not significantly
      affect the sorptive properties of the stream biofilm, providing additional
      evidence that stream biofilms will sorb trace organic compounds under of variety
      of environmental conditions. Because sorption of the target compounds to stream
      biofilms was linearly correlated with organic matter content, hydrophobic
      partition into organic matter appears to be the dominant mechanism. An analysis
      of 17beta-estradiol and 4-nonylphenol hydrophobic partition into water, biofilm,
      sediment, and dissolved organic matter matrices at mass/volume ratios typical of
      smaller rivers showed that the relative importance of the stream biofilm as a
      sorptive matrix was comparable to bed sediments. Therefore, stream biofilms play
      a primary role in attenuating these compounds in surface waters. Because the
      stream biofilm represents the base of the stream ecosystem, accumulation of
      steroidal hormones and 4-nonylphenol compounds in the stream biofilm may be an
      exposure pathway for organisms in higher trophic levels.

PMID- 21846125
TI  - Biosynthesis of unnatural bacteriochlorophyll c derivatives esterified with
      alpha,omega-diols in the green sulfur photosynthetic bacterium Chlorobaculum
      tepidum.
AB  - Unnatural bacteriochlorophyll (BChl) c derivatives possessing a hydroxy group at
      the terminus of a hydrocarbon chain at the 17-propionate were biosynthesized in
      the green sulfur photosynthetic bacterium Chlorobaculum tepidum. Addition of
      exogenous 1,8-octanediol, 1,12-dodecanediol, and 1,16-hexadecanediol in acetone
      to liquid cultures resulted in accumulation of BChl c monoesterified with the
      corresponding diols. The relative ratios of the novel BChl c derivatives
      esterified with 1,8-, 1,12-, and 1,16-diols to totally producing BChl c were 8.2,
      50.2, and 57.6% in the cells grown with additive alpha,omega-diols at
      concentrations of 1.5, 0.06, and 0.06 mM, respectively, at the final
      concentration. The homologue composition of BChl c derivatives esterified with
      these alpha,omega-diols was similar to that of original, coexisting BChl c
      esterified with farnesol (BChl c(F)), suggesting that esterification of
      alpha,omega-diols occurred at the last step of the BChl c biosynthetic pathway by
      BChl c synthase, BchK, in the same manner as in BChl c(F). Chlorosomes, which
      were isolated from cells grown in the presence of exogenous alpha,omega-diols,
      contained a ratio and a composition of BChl c derivatives esterified with the
      diols similar to those in the whole cells, indicating that these BChl c
      derivatives were actually present in chlorosomes. Q(y) absorption bands of C.
      tepidum cells containing the novel BChl c derivatives were shifted to a shorter
      wavelength, although their bandwidths were analogous to those of cells obtained
      by normal cultivation. Circular dichroism spectra of cells that had BChl c
      derivatives esterified with alpha,omega-diols exhibited S-shaped signals in the
      Q(y) region, whose polarities were the reverse of those of cells grown in the
      normal medium and by supplementation with neat acetone as a control experiment.
      These spectral features of C. tepidum possessing BChl c derivatives esterified
      with alpha,omega-diols imply that the novel BChl c derivatives possessing a
      hydroxy group at the terminus of a hydrocarbon chain affect their self-assembly
      in chlorosomes.

PMID- 21846126
TI  - Direct identification of dyes in textiles by direct analysis in real time-time of
      flight mass spectrometry.
AB  - We present here a method requiring no sample preparation for direct
      identification of the organic dye compounds quercetin, indigotin, and alizarin in
      reference materials, in solution, and also in situ in dyed fibers by use of
      direct analysis in real time (DART) ionization and high-resolution time-of-flight
      mass spectrometry. Exact mass determinations on small samples of dyed textiles
      were completed in less than 1 min. With the ability to identify flavonoid,
      indigoid, and anthraquinone classes of dyes, this technique shows early promise
      as an additional analytical tool in the challenging analysis of organic dyes in
      rare cultural heritage materials and possesses the unique advantages of
      sensitivity and simplicity without the preparatory procedures required by other
      methods.

PMID- 21846127
TI  - Kinetics of the oxidation of quercetin by 2,2-diphenyl-1-picrylhydrazyl (dpph*).
AB  - In methanol/water, dpph(*) bleaching (519 nm) by quercetin, QH(2), exhibits
      biphasic kinetics. The dpph(*) reacts completely with the quercetin anion within
      100 ms. Subsequent slower bleaching involves solvent and QH(2) addition to
      quinoid products. The fast reaction is first-order in dpph(*) but only ca. 0.38
      order in [QH(2)]. This extraordinary nonintegral order is attributed to
      reversible formation of pi-stacked {QH(-)/dpph(*)} complexes in which electron
      transfer to products, {QH(*)/dpph(-)}, is slow (k(ET) ~ 10(5) s(-1)).

PMID- 21846128
TI  - Structural and mechanistic analysis of a novel class of shikimate dehydrogenases:
      evidence for a conserved catalytic mechanism in the shikimate dehydrogenase
      family.
AB  - Shikimate dehydrogenase (SDH) catalyzes the reversible NADPH-dependent reduction
      of 3-dehydroshikimate to shikimate. This reaction represents the fourth step of
      the shikimate pathway, the essential route for the biosynthesis of the aromatic
      amino acids in plants, fungi, bacteria, and apicomplexan parasites. The absence
      of this pathway in animals makes it an attractive target for herbicides and
      antimicrobials. At least four functionally distinct enzyme classes, AroE, YdiB,
      SDH-like (SdhL), and AroE-like1 (Ael1), utilize shikimate as a substrate in vitro
      and form the SDH family. Crystal structures have been determined for AroE, YdiB,
      and SdhL. In this study, we have determined the first representative crystal
      structure of an Ael1 enzyme. We demonstrate that Ael1 shares a similar overall
      structure with the other members of the SDH family. This high level of structural
      conservation extends to the active sites of the enzymes. In particular, an
      ionizable active site lysine and aspartate are present in all SDH homologues. Two
      distinct biochemical roles have been reported for this Lys-Asp pair: as binding
      residues in YdiB and as a catalytic dyad in AroE and SdhL. Here, we establish
      that the residues function as a catalytic dyad in Ael1 and, interestingly, in at
      least one YdiB homologue. The conservation of three-dimensional fold, active site
      architecture, and catalytic mechanism among members of the SDH family will
      facilitate the design of drugs targeting the shikimate pathway.

PMID- 21846129
TI  - Molecule and electron transfer through coordination-based molecular assemblies.
AB  - This study provides insight into the internal structure of surface-confined
      molecular assemblies. The permeability of the layer-by-layer grown thin films can
      be controlled systematically by varying their composition and the structure of
      their molecular components. Moreover, the thickness can be used to control
      molecule permeation versus electron transfer.

PMID- 21846130
TI  - Organic triplet excited states of gold(I) complexes with oligo(o- or m
      phenyleneethynylene) ligands: conjunction of steady-state and time-resolved
      spectroscopic studies on exciton delocalization and emission pathways.
AB  - A series of mononuclear and binuclear gold(I) complexes containing oligo(o- or m
      phenyleneethynylene) (PE) ligands, namely [PhC=C(C(6)H(4)-1,2-C=C)(n
      1)Au(PCy(3))] (n = 2-4, 4a-c), [MU-{C=C-(1,2-C(6)H(4)C=C)(n)}{Au(PCy(3))}(2)] (n
      = 1-6, 8, 5a-g), [PhC=C(C(6)H(4)-1,3-C=C)(n-1)Au(PCy(3))] (n = 2-4, 6a-c), and
      [MU-{C=C-(1,3-C(6)H(4)C=C)(n)}{Au(PCy(3))}(2)] (n = 1, 2, 7a,b), were synthesized
      and structurally characterized. Extensive spectroscopic measurements have been
      performed by applying combined methods of femtosecond transient absorption (fs
      TA), fs time-resolved fluorescence (fs-TRF), and nanosecond time-resolved
      emission (ns-TRE) coupled with steady-state absorption and emission spectroscopy
      at both ambient and low (77 K) temperatures to directly probe the temporal
      evolution of the excited states and to determine the dynamics and spectral
      signatures for the involved singlet (S(1)) and triplet (T(1)) excited states. The
      results reveal that S(1) and T(1) both feature ligand-centered electronic
      transitions with pipi* character associated with the phenyl and acetylene
      moieties. The (3)pipi* emission of the PE ligands is switched on by the
      attachment of [Au(PCy(3))](+) fragment(s) due to the heavy-atom effect.
      T(1)((3)pipi*) was found to form with nearly unity efficiency through intersystem
      crossing (ISC) from S(1)((1)pipi*). The ISC time constants were determined to be
      ~50, 35, and 40 ps for 4b and 6a,b, respectively. Dual emission composed of
      fluorescence from S(1) and phosphorescence from T(1) were observed for most of
      the complexes except 5a and 7a, where only phosphorescence was found. The
      fluorescence at ambient temperature is accounted for by both the short-lived
      prompt fluorescence (PF) and long-lived delayed fluorescence (DF, lifetime on
      microsecond time scale). Explicit evidence was presented for a triplet-triplet
      annihilation mechanism for the generation of DF. Ligand length and substitution
      dependent dynamics of T(1) are the key factors governing the dual emission
      character of the complexes. By extrapolation from the plot of emission energy
      against the PE chain length of the [Au(PCy(3))](+) complexes with oligo(o-PE) or
      oligo(m-PE) ligands, the triplet emission energies were estimated to be ~530 and
      ~470 nm for poly(o-PE) and poly(m-PE), respectively. Additionally, we assign the
      unusual red shifts of 983 cm(-1) from [PhC=CAu(PCy(3))] (1) to [MU-{1,3
      (C=C)(2)C(6)H(4)}{Au(PCy(3))}(2)] (7a) and 462 cm(-1) from 7a to [MU(3)-{1,3,5
      (C=C)(3)C(6)H(3)}{Au(PCy(3))}(3)] (8) in the phosphorescence energies to
      excitonic coupling interactions between the C=CAu(PCy(3)) arms in the triplet
      excited states. These complexes, together with those previously reported
      [Au(PCy(3))](+) complexes containing oligo(p-PE) ligands ( J. Am. Chem. Soc. 2002
      , 124 , 14696 - 14706 ), form a collection of oligo(phenyleneethynylene)
      complexes exhibiting organic triplet emission in solution under ambient
      conditions. The remarkable feature of these complexes in exhibiting TTA prompted
      DF in conjunction with high formation efficiency of T(1)((3)pipi*) affords an
      opportunity for emission spectra to cover a wide range of wavelengths. This may
      have implication in the development of PE-based molecular materials for future
      optical applications.

PMID- 21846131
TI  - Enantioselective conjugate addition of alkenylboronic acids to indole-appended
      enones.
AB  - An enantioselective addition of alkenylboronic acids and alkynylboronic esters to
      unprotected indole-appended enones is reported. This transformation proceeds with
      high enantioselectivity and high product yields via the use of catalytic amounts
      of 3,3'-bis(pentafluorophenyl)-BINOL and Mg(Ot-Bu)(2). A range of alpha-branched
      indole derivatives are available from the transformation.

PMID- 21846132
TI  - Lysozyme adsorption on polyethylene surfaces: why are long simulations needed?
AB  - The adsorption of lysozyme onto a polyethylene (PE) surface in an aqueous
      environment was investigated via molecular dynamics (MD) simulation. The
      adsorption can be divided into three processes: diffusion to the surface,
      dehydration induced by hydrophobic surface-protein interactions, and
      denaturation. The dehydration process is very long, around 70 ns. Structural
      deformations start soon after the protein reaches the surface and continue during
      the whole trajectory. The hydrophobic residues are slowly driven toward the
      surface, inducing changes in the protein's secondary structure. The protein's
      secondary structural components near the surface are more disturbed than those
      farther away from the surface. The lysozyme is adsorbed with its long axis
      parallel to the surface and displays an anisotropic mobility on the surface that
      is probably due to the intrinsic structure of the PE surface. Our study
      demonstrates the need for long-time atomistic simulation in order to gain a
      complete understanding of the adsorption process.

PMID- 21846133
TI  - Nanostructural studies on monoelaidin-water systems at low temperatures.
AB  - In recent years, lipid based nanostructures have increasingly been used as model
      membranes to study various complex biological processes. For better understanding
      of such phenomena, it is essential to gain as much information as possible for
      model lipid structures under physiological conditions. In this paper, we focus on
      one of such lipids--monoelaidin (ME)--for its polymorphic nanostructures under
      varying conditions of temperature and water content. In the recent contribution
      (Soft Matter, 2010, 6, 3191), we have reported the phase diagram of ME above 30 
      degrees C and compared with the phase behavior of other lipids including
      monoolein (MO), monovaccenin (MV), and monolinolein (ML). Remarkable phase
      behavior of ME, stabilizing three bicontinuous cubic phases, motivates its study
      at low temperatures. Current studies concentrate on the low-temperature (<30 
      degrees C) behavior of ME and subsequent reconstruction of its phase diagram over
      the entire temperature-water composition space (temperature, 0-76  degrees C; and
      water content, 0-70%). The polymorphs found for the monoelaidin-water system
      include three bicontinuous cubic phases, i.e., Ia3d, Pn3m, and Im3m, and lamellar
      phases which exhibit two crystalline (L(c1) and L(c0)), two gel (L(beta) and
      L(beta*)), and a fluid lamellar (L(alpha)) states. The fluid isotropic phase
      (L(2)) was observed only for lower hydrations (<20%), whereas hexagonal phase
      (H(2)) was not found under studied conditions. Nanostructural parameters of these
      phases as a function of temperature and water content are presented together with
      some molecular level calculations. This study might be crucial for perception of
      the lyotropic phase behavior as well as for designing nanostructural assemblies
      for potential applications.

PMID- 21846134
TI  - Investigation of the low-frequency vibrations of crystalline tartaric acid using
      terahertz spectroscopy and solid-state density functional theory.
AB  - The room temperature and cryogenic terahertz (THz) spectra (10-95 cm(-1)) of l
      tartaric acid and dl-tartaric acid were investigated. At 293 K, the l-tartaric
      acid spectrum showed four absorption features at 36.4, 61.6, 78.7, and 87.3 cm(
      1) in the experimental spectrum. Once cooled to 78 K, these features narrowed and
      shifted to 35.9, 63.4, 81.1, and 90.1 cm(-1). The THz spectrum of dl-tartaric
      acid is significantly different, containing only a single absorption at 79.9 cm(
      1) at room temperature, which shifts to 82.9 cm(-1) at 78 K. Solid-state density
      functional theory calculations [B3LYP/6-311G(2d,2p)] were performed to simulate
      the crystalline structure of both molecular solids and to assign the observed
      spectral features to specific atomic motions. The THz spectrum of l-tartaric acid
      is particularly interesting in that it contains a theoretically unaccounted for
      spectral feature that may arise from second-order phonon processes and also
      exhibits an anomalous red-shifting absorption feature with cooling that is shown
      to originate from negative thermal expansion of the crystal.

PMID- 21846135
TI  - Five-dimensional incommensurate structure of the melilite electrolyte
      [CaNd]2[Ga]2[Ga2O7]2.
AB  - Melilite-type gallium oxides are potential intermediate temperature electrolytes
      for solid oxide fuel cells. Single crystals of [CaNd](2)[Ga](2)[Ga(2)O(7)](2)
      grown using an optical floating zone furnace have been investigated using
      transmission electron microscopy and powder and single-crystal X-ray diffraction.
      The anion array topologically conforms to a [(3.5.4.5)(2), 3.5.3.5] network that
      contains distorted pentagonal tunnels. The distortion is necessary to achieve
      space filling and accommodate structural misfit between the layers. Satisfactory
      bond lengths and angles are obtained through two-dimensional modulation in the
      tetragonal based plane, leading to five-dimensional symmetry in the superspace
      group P(4-)2(1)m(alpha,alpha,0)00s((a-)a,0)000, alpha = 0.2319(2), with
      modulation vectors q(1) = alpha(a* + b*) and q(2) = alpha(-a* + b*). Both
      displacive and occupational modulations are found. Through this mechanism,
      melilites are primed to accommodate mobile oxygen interstitials, suggesting a
      rational approach to crystallochemical tailoring that will enhance ionic
      diffusion and optimize electrolyte performance.

PMID- 21846136
TI  - Integrated sample pretreatment system for N-linked glycosylation site profiling
      with combination of hydrophilic interaction chromatography and PNGase F
      immobilized enzymatic reactor via a strong cation exchange precolumn.
AB  - An integrated sample pretreatment system, composed of a click maltose hydrophilic
      interaction chromatography (HILIC) column, a strong cation exchange (SCX)
      precolumn, and a PNGase F immobilized enzymatic reactor (IMER), was established
      for the simultaneous glycopeptide enrichment, sample buffer exchange, and online
      deglycosylation, by which the sample pretreatment for glycoproteome could be
      performed online automatically, beneficial to improve the efficiency and
      sensitivity of the N-linked glycosylation site identification. With such a
      system, the deglycosylated glycopeptide from the digests of avidin with the
      coexistence of 50 times (mass ratio) BSA could be selectively detected, and the
      detection limit as low as 5 fmol was achieved. Moreover, the sample pretreatment
      time was significantly shortened to ~1 h. Such a system was further successfully
      applied for analyzing the digest of the soluble fraction extracted from rat
      brain. A total of 120 unique glycoprotein groups and 196 N-linked glycosylation
      sites were identified by nanoreversed phase liquid chromatography-electrospray
      ionization-tandem mass spectrometry (nanoRPLC-ESI-MS/MS), with the injected
      digests amount as 6 MUg. All these results demonstrate that the integrated system
      is of great promise for N-linked glycosylation site profiling and could be
      further online coupled with nanoHPLC-ESI-MS/MS to achieve high-throughput
      glycoproteome analysis.

PMID- 21846137
TI  - Control of the fluorescence of dye-antibody conjugates by (2-hydroxypropyl)-beta
      cyclodextrin in fluorescence microscopy and flow cytometry.
AB  - When proteins are conjugated to fluorescent organic dyes, fluorescence emission
      of the dye molecules is usually decreased, sometimes up to 50-70%. This quenching
      phenomenon has been acknowledged for decades, but as yet, there are no simple,
      practical methods to control the fluorescence of dyes conjugated to proteins,
      especially for dyes conjugated to immunoglobulins. Here, we report that the
      addition of (2-hydroxypropyl)-beta-cyclodextrin (HPbetaCD) to dye-antibody
      conjugates can increase fluorescence up to 2.5-fold in cell imaging and flow
      analysis. This method may be an effective way to increase the sensitivity of
      detection of fluorescent organic labels used in immunology, histochemistry, and
      cell biology.

PMID- 21846138
TI  - Scalable, stereocontrolled total syntheses of (+/-)-axinellamines A and B.
AB  - The development of a simple, efficient, scalable, and stereocontrolled synthesis
      of a common intermediate en route to the axinellamines, massadines, and
      palau'amine is reported. This completely new route was utilized to prepare the
      axinellamines on a gram scale. In a more general sense, three distinct and
      enabling methodological advances were made during these studies: (1) an ethylene
      glycol-assisted Pauson-Khand cycloaddition reaction, (2) a Zn/In-mediated Barbier
      type reaction, and (3) a TfNH(2)-assisted chlorination-spirocyclization.

PMID- 21846139
TI  - Inhibitors of androgen receptor activation function-2 (AF2) site identified
      through virtual screening.
AB  - The androgen receptor (AR) is one of the most studied drug targets for the
      treatment of prostate cancer. However, all current anti-androgens directly
      interact with the AR at the androgen binding site, which is prone to resistant
      mutations, calling for new strategies of the AR inhibition. The current study
      represents the first attempt to use virtual screening to identify inhibitors of
      activation function-2 (AF2) of the human AR. By combining large-scale docking
      with experimental approaches, we were able to identify several small molecules
      that interact with the AF2 and effectively prevent the transcriptional activation
      of the AR. The crystallographic structure of one of these inhibitors in complex
      with the AR provides critical insight into the corresponding protein-ligand
      interactions and suitable for future hit optimization. Taken together, our
      results provide a promising ground for development of novel anti-androgens that
      can help to address the problem of drug resistance in prostate cancer.

PMID- 21846140
TI  - Critical assessment of the formation of ionic-liquid-based aqueous two-phase
      systems in acidic media.
AB  - In this work, the ability of Na(2)SO(4) and ionic liquids to induce the formation
      of acidic aqueous two-phase systems (ATPS) is investigated. Ternary phase
      diagrams, tie lines, and tie-line lengths for several systems were determined and
      reported at 298 K and atmospheric pressure. It is here shown that among the ionic
      liquids studied only those containing long alkyl side chains at the ions and/or
      anions with low hydrogen bond basicity are capable of undergoing liquid-liquid
      demixing in the presence of Na(2)SO(4) aqueous solutions. The results obtained
      indicate that, besides the salting-out ability of the inorganic salt, the pH of
      the aqueous solution plays a crucial role toward the formation of ionic-liquid
      based ATPS. In acidic media the range of ionic liquids that are able to undergo
      ATPS formation is substantially reduced when compared to alkaline aqueous salt
      solutions. The use of inorganic salts and ionic liquids to promote acidic ATPS is
      envisaged as particularly valuable in the extraction of compounds that exhibit
      low acid dissociation constants.

PMID- 21846141
TI  - Composition and mechanism of antitumor effects of Hericium erinaceus mushroom
      extracts in tumor-bearing mice.
AB  - We investigated antitumor effects of the following four extracts of freeze-dried
      Hericium erinaceus mushrooms in Balb/c mice intracutaneously transplanted on the
      backs with CT-26 colon cancer cells: HWE, hot water extraction by boiling in
      water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W for 3 min; and ACE
      and AKE, boiling in 1% HCl or 3% NaOH for 2 h. HWE and MWE with a higher content
      of beta-glucans, determined by an assay kit, than ACE and MKE were active in all
      bioassays. Gas chromatography/mass spectrometry analyses showed the presence of
      40, 27, 16, and 13 compounds, respectively, in the four extracts. Daily
      intraperitoneal (ip) injections of HWE and MWE for 2 weeks significantly reduced
      tumor weights by 38 and 41%. Tumor regressions were associated with changes in
      the following cancer biomarkers as compared to phosphate buffer (PBS)-treated
      control mice: 2.7- and 2.4-fold increases in cytolytic activity of splenic
      natural killer (NK) cells; restored nitric oxide production and phagocytosis in
      peritoneal macrophages to 95-98% of normal levels; ~2-fold increase in released
      pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6 from macrophages; and ~56 and ~60% reductions in the number of
      blood vessels inside the tumor. The pro-angiogenic factors vascular endothelial
      growth factor (VEGF), cyclooxygenase 2 (COX-2), and 5-lipoxygenase (5-LOX) were
      also significantly reduced in mRNA and protein expression by tumor genes. Enzyme
      linked immunosorbent assay of tumor cells confirmed reduced expression of COX-2
      and 5-LOX (32 and 31%). Reduced COX-2 and 5-LOX expression down-regulated VEGF
      expression, resulting in inhibition of neo-angiogenesis inside the tumors. The
      results indicate that induction of NK activity, activation of macrophages, and
      inhibition of angiogenesis all contribute to the mechanism of reduction of tumor
      size.

PMID- 21846142
TI  - Single-run electrochemical determination of melamine in dairy products and pet
      foods.
AB  - A simple electrochemical approach, which does not require any expensive and
      complex instruments, is established for the selective and quantitative
      recognition of melamine in diary products and pet foods. During a
      preconcentration step (at 1.8 V versus Ag/AgCl), the formation of a polymer film
      from melamine on a preanodized screen-printed carbon electrode was identified by
      SEM and XPS. The as-formed polymer was found to be electroactive with a
      reversible redox peak, and hence square-wave voltammetry was applied to further
      increase the detection sensitivity to meet the detection limit for application in
      real sample analysis. Simply with a medium exchange procedure, melamine was
      selectively detected with a detection limit (S/N=3) of 0.8 MUM (i.e., 98.3 ppb)
      by square-wave voltammetry. Lower than 1 ppm of melamine in real samples can be
      easily detected with good recoveries of 98.7-100.9% by the proposed approach. The
      recovery tests established for external calibration and standard addition
      techniques verified that the analysis can be done in a single-run measurement.

PMID- 21846143
TI  - Dual path mechanism in the thermal reduction of graphene oxide.
AB  - Graphene is easily produced by thermally reducing graphene oxide. However, defect
      formation in the C network during deoxygenation compromises the charge carrier
      mobility in the reduced material. Understanding the mechanisms of the thermal
      reactions is essential for defining alternative routes able to limit the density
      of defects generated by carbon evolution. Here, we identify a dual path mechanism
      in the thermal reduction of graphene oxide driven by the oxygen coverage: at low
      surface density, the O atoms adsorbed as epoxy groups evolve as O(2) leaving the
      C network unmodified. At higher coverage, the formation of other O-containing
      species opens competing reaction channels, which consume the C backbone. We
      combined spectroscopic tools and ab initio calculations to probe the species
      residing on the surface and those released in the gas phase during heating and to
      identify reaction pathways and rate-limiting steps. Our results illuminate the
      current puzzling scenario of the low temperature gasification of graphene oxide.

PMID- 21846144
TI  - Bioconjugation of neutral protease on silk fibroin nanoparticles and application
      in the controllable hydrolysis of sericin.
AB  - Bombyx mori silk fibroin is a protein-based macromolecular biopolymer with
      remarkable biocompatibility. Silk fiber was degummed and subjected to a series of
      treatments, including dissolution and dialysis, to yield an aqueous solution of
      silk fibroin, which was introduced rapidly into excess acetone to produce
      crystalline silk fibroin nanoparticles (SFNs). The SFNs were conjugated
      covalently with a neutral protease (NP) using glutaraldehyde as the cross-linking
      reagent. The objective of this study was to determine the optimal conditions for
      biosynthesis of the SFN-NP bioconjugates. First, SFN-NP was obtained by covalent
      cross-linking of SFN and NP at an SFN/NP ratio of 5-8 mg:1 IU with 0.75%
      glutaraldehyde for 6 h at 25  degrees C. When adding 50 IU of the enzyme, the
      residual activity of biological conjugates was increased to 31.45%. Studies on
      the enzyme activity of SFN-NP and its kinetics showed that the stability of SFN
      NP bioconjugates was greater than that of the free enzyme, the optimum reactive
      temperature range was increased by 5-10  degrees C, and the optimum pH value
      range was increased to 6.5-8.0. Furthermore, the thermal stability was improved
      to some extent. A controlled hydrolysis test using the poorly water-soluble
      protein sericin as a substrate and SFN-NP as the enzyme showed that the longer
      the reaction time (within 1 h), the smaller the molecular mass (<30 kDa) is of
      the sericin peptide produced. The SFN-NP bioconjugate is easily recovered by
      centrifugation and can be used repeatedly. The highly efficient processing
      technology and the use of SFN as a novel vector for a protease has great
      potential for research and the development of food processing.

PMID- 21846145
TI  - Solvation and crystal effects in bilirubin studied by NMR spectroscopy and
      density functional theory.
AB  - The open-chain tetrapyrrole compound bilirubin was investigated in chloroform and
      dimethyl sulfoxide solutions by liquid-state NMR and as solid by (1)H, (13)C, and
      (15)N magic-angle spinning (MAS) solid-state NMR spectroscopy. Density functional
      theory (DFT) calculations were performed to interpret the data, using the B3LYP
      exchange-correlation functional to optimize geometries and to compute NMR
      chemical shieldings by the gauge-including atomic orbital method. The dependence
      of geometries and chemical shieldings on the size of the basis sets was
      investigated for the reference molecules tetramethylsilane, NH(3), and H(2)O, and
      for bilirubin as a monomer and in clusters consisting of up to six molecules. In
      order to assess the intrinsic errors of the B3LYP approximation in calculating
      NMR shieldings, complete basis set estimates were obtained for the nuclear
      shielding values of the reference molecules. The experimental liquid-state NMR
      data of bilirubin are well reproduced by a monomeric bilirubin molecule using the
      6-311+G(2d,p) basis set for geometry optimization and for calculating chemical
      shieldings. To simulate the bilirubin crystal, a hexameric model was required. It
      was constructed from geometry-optimized monomers using information from the X-ray
      structure of bilirubin to fix the monomeric entities in space and refined by
      partial optimization. Combining experimental (1)H-(13)C and (1)H-(15)N NMR
      correlation spectroscopy and density functional theory, almost complete sets of
      (1)H, (13)C, and (15)N chemical shift assignments were obtained for both liquid
      and solid states. It is shown that monomeric bilirubin in chloroform solution is
      formed by 3-vinyl anti conformers, while bilirubin crystals are formed by 3-vinyl
      syn conformers. This conformational change leads to characteristic differences
      between the liquid- and solid-state NMR resonances.

PMID- 21846147
TI  - Human immunoglobulin E (IgE) binding to heated and glycated ovalbumin and
      ovomucoid before and after in vitro digestion.
AB  - This study focuses on the effect of heating and Maillard reaction (MR) on the in
      vitro digestibility and rabbit IgG- and human IgE-binding properties of ovalbumin
      (OVA) and ovomucoid (OM) to estimate the impact of processing on their
      allergenicity. With the human sera studied, heat treatment significantly reduced
      IgE binding to both OVA and OM, whereas MR reduced the IgE binding to OVA but
      increased IgE binding to OM. In contrast, heat treatment significantly favored
      OVA digestibility but glycation impaired it, and these treatments did not affect
      the digestibility of OM. The changes observed in the digestibility affected the
      immunogenicity of the digests accordingly, so that the higher the digestibility,
      the lower the antibody binding. Heat treatment and glycation by MR showed an
      influence on the potential allergenicity of the main egg white proteins that
      could be related to their resistance to denaturation and digestive enzymes.

PMID- 21846146
TI  - Assessing helical protein interfaces for inhibitor design.
AB  - Structure-based design of synthetic inhibitors of protein-protein interactions
      (PPIs) requires adept molecular design and synthesis strategies as well as
      knowledge of targetable complexes. To address the significant gap between the
      elegant design of helix mimetics and their sporadic use in biology, we analyzed
      the full set of helical protein interfaces in the Protein Data Bank to obtain a
      snapshot of how helices that are critical for complex formation interact with the
      partner proteins. The results of this study are expected to guide the systematic
      design of synthetic inhibitors of PPIs. We have experimentally evaluated new
      classes of protein complexes that emerged from this data set, highlighting the
      significance of the results described herein.

PMID- 21846149
TI  - Dynamics of nucleosomes assessed with time-lapse high-speed atomic force
      microscopy.
AB  - A fundamental challenge of gene regulation is the accessibility of DNA within
      nucleosomes. Recent studies performed by various techniques, including single
      molecule approaches, led to the realization that nucleosomes are quite dynamic
      rather than static systems, as they were once considered. Direct data are needed
      to characterize the dynamics of nucleosomes. Specifically, if nucleosomes are
      dynamic, the following questions need to be answered. What is the range of
      nucleosome dynamics? Is a non-ATP-dependent unwrapping of nucleosomes possible?
      What are the factors facilitating the large-scale opening and unwrapping of
      nucleosomes? In previous studies using time-lapse atomic force microscopy (AFM)
      imaging, we were able, for the first time, to observe spontaneous, ATP
      independent unwrapping of nucleosomes. However, low temporal resolution did not
      allow visualization of various pathways of nucleosome dynamics. In the studies
      described here, we applied high-speed time-lapse AFM (HS-AFM) capable of
      visualizing molecular dynamics on the millisecond time scale to study the
      nucleosome dynamics. The mononucleosomes were assembled on a 353 bp DNA substrate
      containing nucleosome-specific 601 sequence. With HS-AFM, we were able to observe
      the dynamics of nucleosome on a subsecond time scale and visualize various
      pathways of nucleosome dynamics, such as sliding and unwrapping to various
      extents, including complete dissociation. These studies highlight an important
      role of electrostatic interactions in chromatin dynamics. Overall, our findings
      shed new light on nucleosome dynamics and provide a novel hypothesis for the
      mechanisms controlling the spontaneous dynamics of chromatin.

PMID- 21846150
TI  - Self-sorting phenomena in complex supramolecular systems.

PMID- 21846151
TI  - Direct detection of beta-agonists by use of gold nanoparticle-based colorimetric
      assays.
AB  - beta-Agonists fed to animals for human consumption pose a serious threat to human
      health. Fast, broad-spectrum detection methods are needed for on-site screening
      of various types of beta-agonists from animal feeds, meats, and animal body
      fluids. We developed a colorimetric assay that uses gold nanoparticle (AuNP)
      plasmon absorption to realize quick detection of beta-agonists from liquid
      samples. beta-Agonists showed the capability of directly reducing HAuCl(4) into
      atomic gold, which involved oxidation of the amine or phenol group on the benzene
      ring of the beta-agonists. The resulting atomic gold formed AuNPs spontaneously,
      which had strong plasmon absorption at 528 nm. The linear relationship between
      the concentrations of beta-agonists and the AuNPs plasmon absorbance granted
      quantitative determination of beta-agonists in solution. The AuNPs colorimetric
      assay showed different sensitivities toward beta-agonists with different
      substituent groups on the aromatic ring. beta-Agonists with phenol groups had a
      lower limit of quantitation (LOQ) than those with amine groups. High-resolution
      transmission electron microscopy (TEM) images revealed the sizes of the AuNPs
      were in the range 15-25 nm, while X-ray energy-dispersive spectroscopic data
      suggested the smaller particles observed in TEM with lower contrast may be salt
      particles from the buffer solution. The developed colorimetric assay can
      potentially be used for the detection of beta-agonists and their analogues from
      serum, urine, and other liquid samples in the presence of interference from
      common antibiotics and glucose.

PMID- 21846152
TI  - Mechanistic insights for block copolymer morphologies: how do worms form
      vesicles?
AB  - Amphiphilic diblock copolymers composed of two covalently linked, chemically
      distinct chains can be considered to be biological mimics of cell membrane
      forming lipid molecules, but with typically more than an order of magnitude
      increase in molecular weight. These macromolecular amphiphiles are known to form
      a wide range of nanostructures (spheres, worms, vesicles, etc.) in solvents that
      are selective for one of the blocks. However, such self-assembly is usually
      limited to dilute copolymer solutions (<1%), which is a significant disadvantage
      for potential commercial applications such as drug delivery and coatings. In
      principle, this problem can be circumvented by polymerization-induced block
      copolymer self-assembly. Here we detail the synthesis and subsequent in situ self
      assembly of amphiphilic AB diblock copolymers in a one pot concentrated aqueous
      dispersion polymerization formulation. We show that spherical micelles, wormlike
      micelles, and vesicles can be predictably and efficiently obtained (within 2 h of
      polymerization, >99% monomer conversion) at relatively high solids in purely
      aqueous solution. Furthermore, careful monitoring of the in situ polymerization
      by transmission electron microscopy reveals various novel intermediate structures
      (including branched worms, partially coalesced worms, nascent bilayers, "octopi",
      "jellyfish", and finally pure vesicles) that provide important mechanistic
      insights regarding the evolution of the particle morphology during the sphere-to
      worm and worm-to-vesicle transitions. This environmentally benign approach (which
      involves no toxic solvents, is conducted at relatively high solids, and requires
      no additional processing) is readily amenable to industrial scale-up, since it is
      based on commercially available starting materials.

PMID- 21846153
TI  - Click approaches to functional water-sensitive organotriethoxysilanes.
AB  - The derivatization of functional organic fragments with triethoxysilyl groups to
      afford hydrolyzable organosilanes with targeted properties using the copper
      catalyzed alkyne azide cycloaddition reaction under strictly anhydrous conditions
      is described according to two approaches, starting from five silylated
      substrates. This high yield, fast, and selective method is applicable to a wide
      range of substrates and is expected to lead to important achievements in the
      field of functional hybrid silica.

PMID- 21846154
TI  - Aliskiren as add-on therapy in the treatment of hypertensive diabetic patients
      inadequately controlled with valsartan/HCT combination: a placebo-controlled
      study.
AB  - BACKGROUND: Hypertension frequently coexists with diabetes mellitus, resulting in
      increased cardiovascular risk. Thus, BP control is crucial in decreasing
      morbidity and mortality in this difficult-to-treat patient population. OBJECTIVE:
      The objective of this study was to evaluate the efficacy and safety of aliskiren
      in hypertensive patients with diabetes not adequately responsive to the
      combination of valsartan and hydrochlorothiazide (HCT). METHODS: After a 1- to 4
      week washout period, patients with a mean sitting diastolic BP (msDBP) >=95 mmHg
      were treated with valsartan 160 mg for 2 weeks followed by valsartan/HCT 160
      mg/25 mg for an additional 4 weeks (single-blind active run-in period). Patients
      whose msDBP remained >=85 mmHg after the active run-in period were randomized (1
      : 1) to receive aliskiren 150 mg (n = 184) or placebo (n = 179) as add-on therapy
      for 6 weeks. Aliskiren was then force-titrated to 300 mg once daily for another 6
      weeks. Efficacy variables were: the change in msDBP and mean sitting systolic BP
      (msSBP) from baseline to week 12 endpoint, diastolic response (msDBP <80 mmHg or
      reduction of at least 10 mmHg), and BP control rate (<130/80 mmHg). RESULTS: Of
      the 363 patients randomized, 328 (90.4%) completed the study (aliskiren and
      placebo groups: 89.7% and 91.1%, respectively). At week 12 endpoint, the least
      squares mean (LSM) changes in msDBP (aliskiren vs placebo: -5.8 vs -4.8 mmHg; p =
      0.2767) and msSBP (aliskiren vs placebo: -7.3 vs -4.8 mmHg; p = 0.0725) were
      numerically greater in patients treated with aliskiren compared with those
      treated with placebo; however, this difference was not statistically significant.
      The proportion of diastolic responders (aliskiren and placebo: 68.5% and 72.9%,
      respectively; p = 0.8482) and patients achieving BP control (aliskiren and
      placebo: 16.0% and 16.4%, respectively; p = 0.7511) were similar for both groups.
      Overall, 63 (34%) and 59 (33%) patients in the aliskiren and placebo groups,
      respectively, experienced adverse events (AEs). The most commonly reported AEs
      were headache (placebo group: 6.1%) and dizziness (aliskiren group: 4.4%).
      Aliskiren was well tolerated. CONCLUSION: The reductions in BP with aliskiren
      added to valsartan/HCT in this study were numerically greater compared with
      placebo added to valsartan/HCT, although not statistically significant.

PMID- 21846155
TI  - Extracorporeal shock wave therapy for ischemic cardiovascular disorders.
AB  - Ischemic heart disease is the leading cause of death and a major cause of
      hospital admissions, with the number of affected patients increasing worldwide.
      The current management of ischemic heart disease has three major therapeutic
      options: medication, percutaneous coronary intervention (PCI), and coronary
      artery bypass grafting (CABG). However, the prognosis for patients with severe
      ischemic heart disease without indications for PCI or CABG still remains poor due
      to the lack of effective treatments. It is therefore crucial to develop
      alternative therapeutic strategies for severe ischemic heart disease.
      Extracorporeal shock wave (SW) therapy was introduced clinically more than 20
      years ago to fragment kidney stones, which has markedly improved the treatment of
      urolithiasis. We found that a low-energy SW (about 10% of the energy density used
      for urolithiasis) effectively increases the expression of vascular endothelial
      growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study,
      we initiated in vivo studies and have demonstrated that extracorporeal cardiac SW
      therapy with a low-energy SW up-regulates the expression of VEGF, induces
      neovascularization, and improves myocardial ischemia in a porcine model of
      chronic myocardial ischemia, without any adverse effects in vivo. On the basis of
      promising results in animal studies, we performed a series of clinical studies in
      patients with severe coronary artery disease without indication for PCI or CABG,
      including, firstly, an open trial followed by a placebo-controlled, double-blind
      study. In both studies, our extracorporeal cardiac SW therapy improved symptoms,
      exercise capacity, and myocardial perfusion in patients with severe coronary
      artery disease. Importantly, no procedural complications or adverse effects were
      noted. The SW therapy was also effective in ameliorating left ventricular
      remodeling after acute myocardial infarction (MI) in pigs and in enhancing
      angiogenesis in hind-limb ischemia in rabbits. Based on these animal studies, we
      are also conducting clinical studies in patients with acute MI and in those with
      peripheral artery disease. Thus, our extracorporeal cardiac SW therapy appears to
      be an effective, safe, and non-invasive angiogenic approach in cardiovascular
      medicine and its indication could be extended to a variety of ischemic diseases
      in the near future. In this article, we briefly summarize our work in animals and
      humans, and discuss the advantages and perspectives of our extracorporeal SW
      therapy.

PMID- 21846156
TI  - Lomitapide.
AB  - Aegerion Pharmaceuticals is developing lomitapide, a small-molecule, microsomal
      triglyceride transfer protein (MTP) inhibitor, for the treatment of both familial
      and primary hypercholesterolemia. Oral, once-daily lomitapide will be targeted at
      patients resistant to HMG-CoA reductase inhibitors (statins) either due to
      abnormalities in liver function or to discontinuation because of muscle pain. An
      oral formulation of lomitapide is in phase III development for homozygous
      familial hypercholesterolemia (hyperlipoproteinemia type IIa) in the US, Canada,
      Italy, and South Africa. This review discusses the key development milestones and
      therapeutic trials of this drug.

PMID- 21846157
TI  - The role of direct renin inhibition in clinical practice: focus on combination
      therapy.
AB  - Monotherapy with most antihypertensive agents reduces systolic BP by about 10
      mmHg ('Rule of 10'). Thus, the majority of hypertensive patients require
      combination therapy to achieve BP goals. In this review, we provide a brief
      overview of the renin-angiotensin-aldosterone system (RAAS) and discuss the
      rationale, clinical evidence, and shortcomings related to the use of angiotensin
      converting enzyme (ACE) inhibitors in combination with angiotensin II type 1
      receptor antagonists (angiotensin receptor blockers [ARBs]). We summarize the
      rationale and clinical evidence supporting the use of the direct renin inhibitor
      (DRI) aliskiren, particularly in combination with other antihypertensive classes,
      including in high-risk patients with diabetes mellitus and with or without
      diabetic nephropathy. DRIs may be useful in combination with ACE inhibitors or
      ARBs as they provide a more complete blockade of the RAAS, effectively
      suppressing residual angiotensin II production and the counter-regulatory
      increase in plasma renin activity observed in patients receiving monotherapy with
      ACE inhibitors or ARBs.

PMID- 21846158
TI  - Years of potential life lost and indirect costs of melanoma and non-melanoma skin
      cancer: a systematic review of the literature.
AB  - Skin cancer is the most common form of cancer in the US, and an important public
      health concern both in the US and throughout the world. Given high incidence
      rates among young adults and the large number of deaths, skin cancer has the
      potential to result in significant years of potential life lost (YPLL) and lost
      productivity. The purpose of this study was to systematically review the
      published literature on the YPLL and the value of productivity loss from
      morbidity and premature mortality resulting from melanoma and non-melanoma skin
      cancer (NMSC). Employing pre-defined search terms and inclusion/exclusion
      criteria, systematic searches were conducted in MEDLINE, EMBASE, CINAHL and
      Econlit. We selected studies that measured the societal burden of melanoma and
      NMSC - through estimating either the YPLL and/or the indirect costs. We
      identified 16 relevant studies meeting our criteria, six were from the US and ten
      were from other industrialized countries; ten of the studies reported results on
      YPLL, eight on mortality costs and five on morbidity costs. Some studies reported
      results in more than one category. From each eligible article and report, we
      extracted detailed information on the study population/country, study design,
      data analysis methods and study results. Data abstracted for each eligible study
      included estimated number of YPLL, YPLL per death and morbidity and mortality
      costs. The average number of YPLL per death was approximately 15 for melanoma and
      10 for NMSC. We found the costs attributable to melanoma and NMSC ranged from
      $US39.2 million to $US28.9 million for morbidity and $US3.3 billion to $US1.0
      billion for mortality, respectively. It is clear from the published literature
      that skin cancer leads to significant YPLL and indirect costs associated with
      premature mortality and morbidity. Prevention and early detection efforts are
      important in helping reduce the incidence of melanoma and NMSC, and the related
      deaths and productivity losses.

PMID- 21846159
TI  - Metformin-induced leukocytoclastic vasculitis: a case report.

PMID- 21846160
TI  - A model to estimate the potential for a physical activity-induced reduction in
      healthcare costs for the elderly, based on pedometer/accelerometer data from the
      Nakanojo Study.
AB  - The rising healthcare costs associated with an aging population have become an
      urgent fiscal problem. However, evidence of the efficacy of preventive programmes
      is limited, since almost all studies have involved only small numbers of highly
      selected participants. This article examines potential physical activity-induced
      decreases in healthcare expenses, applying a theoretical model to the Nakanojo
      Study of habitual physical activity and health in an entire elderly community.
      The Nakanojo Study has shown substantial associations of health with both step
      count and the duration of moderate effort (intensity >3 metabolic equivalents
      [METs]). Participants are classed as 'dependent' (n = 800) or 'independent' (n =
      4400); the latter category is divided arbitrarily into quartiles, based on
      physical activity patterns (Q1-Q4; n = 1100 for each quartile). The five groups
      show a graded prevalence of various morbidities, including dependency,
      depression, osteoporosis, fractures, hypertension, diabetes mellitus,
      hyperlipidaemia, ischaemic heart diseases, cerebrovascular diseases, cancer and
      dementia. Consequently, annual healthcare expenditures (based on 2009 published
      Japanese costs associated with each of these conditions) differ by about yen
      (Y)197 900 ($US1979) per person between dependent individuals and those in group
      Q1, Y20 700 ($US207) between Q1 and Q2, Y14 600 ($US146) between Q2 and Q3, and
      Y5300 ($US53) between Q3 and Q4. Accepting a causal relationship between physical
      activity and health, and assuming that an increase in physical activity induces a
      benefit that is uniform across conditions and diseases, respective morbidity
      prevalences and associated healthcare costs seem likely to decrease as physical
      activity increases. Thus, if the physical activity of only 5% of each group could
      be increased by a single ranking (pedometer/accelerometer scores of 2000
      steps/day and 5-10 min/day at >3 METs and/or an adjusted questionnaire score of
      10 MET hours/week), one might predict average savings across this population of
      about Y12 600 ($US126) per person, or 3.7%, of total medical expenses, including
      Y9800 ($US98) of public nursing care insurance costs and an additional Y2800
      ($US28) of national health insurance expenditures. The impact of various changes
      in the prevalence of physical activity can be simulated using our model. In
      principle, savings should increase if more people increase their physical
      activity, and/or the magnitude of individual increases in physical activity is
      greater. Nevertheless, our analysis suggests that if even a small fraction of
      individuals in the three least active groups were to make a single-rank increase
      in their habitual physical activity as a result of focused health support and the
      promotion of physical activity, a significant reduction in medical expenses might
      be anticipated, justifying investment in preventive programmes. We now propose to
      test the validity of the present simulations on a national basis, obtaining
      accurate and objective evidence of change in individual physical activity
      patterns using an advanced design of pedometer/accelerometer.

PMID- 21846161
TI  - Skin conditions in figure skaters, ice-hockey players and speed skaters: part I -
      mechanical dermatoses.
AB  - Figure skaters, ice-hockey players and speed skaters experience a range of
      dermatologic conditions and tissue-related injuries on account of mechanical
      trauma, infectious pathogens, inflammatory processes and environmental factors
      related to these competitive pursuits. Sports medicine practitioners, family
      physicians, dermatologists and coaches should be familiar with these skin
      conditions to ensure timely and accurate diagnosis and management of affected
      athletes. This review is Part I of a subsequent companion review and provides a
      comprehensive review of mechanical dermatoses experienced by ice-skating
      athletes, including skater's nodules and its variants, pump bumps, piezogenic
      pedal papules, talon noir, skate/lace bite, friction bullae, corns and calluses,
      onychocryptosis, skater's toe and skate blade-induced lacerations. These injuries
      result from friction, shear forces, chronic pressure and collisions with surfaces
      that occur when athletes endure repetitive jump landings, accelerated starts and
      stops and other manoeuvres during rigorous training and competition. Ill-fitting
      skates, improper lacing techniques and insufficient lubrication or protective
      padding of the foot and ankle often contribute to the development of skin
      conditions that result from these physical and mechanical stresses. As we will
      explain, simple measures can frequently prevent the development of these
      conditions. The treatment of skater's nodules involves reduction in chronic
      stimulation of the malleoli, and the use of keratolytics and intralesional
      steroid injections; if malleolar bursitis develops, bursa aspirations may be
      required. Pump bumps, which result from repetitive friction posteriorly, can be
      prevented by wearing skates that fit correctly at the heel. Piezogenic pedal
      papules may be treated conservatively by using heel cups, compressive stockings
      and by reducing prolonged standing. Talon noir usually resolves without
      intervention within several weeks. The treatment of skate bite is centred on
      reducing compression by the skate tongue of the extensor tendons of the anterior
      ankle, which can be accomplished by use of proper lacing techniques, increasing
      pliability of the skate tongue and using protective padding, such as Bunga
      PadsTM. Anti-inflammatory medications and cold compresses can also help reduce
      inflammation. Friction bullae are best managed by careful lancing of painful
      blisters and application of petrolatum or protective dressings to accelerate
      healing; preventative measures include the use of well fitting skates, proper
      lacing techniques and moisture-wicking socks. Corns and calluses are similarly
      best prevented by the use of well fitted skates and orthotic devices.
      Symptomatic, debridement reduces the irritant effect of the thick epidermis, and
      can be accomplished by soaking the area in warm water followed by paring.
      Application of creams with high concentrations of urea or salicylic acid can also
      soften callosities. Cases of onychocryptosis benefit from warm soaks, antibiotic
      ointments and topical steroids to reduce inflammation, but sometimes chemical or
      surgical matricectomies are required. Preventative measures of both
      onychocryptosis and skater's toe include cutting toenails straight across to
      allow for a more equal distribution of forces within the toe box. Finally, the
      prevention and treatment of lacerations, which constitute a potentially fatal
      type of mechanical injury, require special protective gear and acute surgical
      intervention with appropriate suturing. The subsequent companion review of skin
      conditions in ice skaters will discuss infectious, inflammatory and cold-induced
      dermatoses, with continued emphasis on clinical presentation, diagnosis,
      treatment and prevention.

PMID- 21846162
TI  - Amputees and sports: a systematic review.
AB  - Amputation of a limb may have a negative impact on the psychological and physical
      well-being, mobility and social life of individuals with limb amputations.
      Participation in sports and/or regular physical activity has a positive effect on
      the above mentioned areas in able-bodied individuals. Data concerning
      participation in sports or regular physical activity together with its benefits
      and risks for individuals with limb amputations are scarce. No systematic review
      exists that addresses a wide range of outcomes such as biomechanics,
      cardiopulmonary function, psychology, sport participation and sport injuries.
      Therefore, the aim of this article is to systematically review the literature
      about individuals with limb amputations and sport participation. MEDLINE
      (PubMed), EMBASE, CINAHL(r) and SportDiscus(r) were searched without time or
      language restrictions using free text words and MeSH terms. The last search date
      was 31 March 2010. Books, internet sites and references of included papers were
      checked for papers relevant to the topic under review. Papers were included if
      the research topic concerned sports and a minimum of ten individuals with limb
      amputations were part of the study population. Papers were excluded if they
      included individuals with amputations of body parts other than upper or lower
      limbs or more distal than the wrist or ankle, or if they consisted of case
      reports, narrative reviews, books, notes or letters to the editor. Title,
      abstract and full-text assessments were performed by two independent observers
      following a list of preset criteria. Of the 3689 papers originally identified, 47
      were included in the review. Most of the included studies were older than 10
      years and had cross-sectional designs. Study participants were generally younger
      and often had more traumatic amputations than the general population of
      individuals with limb amputations. Heterogeneity in population characteristics,
      intervention types and main outcomes made data pooling impossible. In general,
      sports were associated with a beneficial effect on the cardiopulmonary system,
      psychological well-being, social reintegration and physical functioning. Younger
      individuals with unilateral transtibial amputations achieve better athletic
      performance and encounter fewer problems when participating in sports compared
      with older individuals with bilateral transfemoral amputations. Regardless of
      their amputation level, individuals with limb amputations participate in a wide
      range of recreational activities. The majority of them were not aware of the
      sport facilities in their area and were not informed about available recreational
      activities. Sport prosthetic devices were used mostly by competitive athletes.
      For football, the injury rate and pattern of the players with an amputation were
      similar to those of able-bodied players. Individuals with limb amputations appear
      to benefit both physically and psychologically from participation in sports
      and/or regular physical activity. Therefore, sports should be included in
      rehabilitation programmes, and individuals with limb amputations should be
      encouraged to pursue a physically active life following hospital discharge.

PMID- 21846163
TI  - Repeated-sprint ability - part II: recommendations for training.
AB  - Short-duration sprints, interspersed with brief recoveries, are common during
      most team sports. The ability to produce the best possible average sprint
      performance over a series of sprints (<=10 seconds), separated by short (<=60
      seconds) recovery periods has been termed repeated-sprint ability (RSA). RSA is
      therefore an important fitness requirement of team-sport athletes, and it is
      important to better understand training strategies that can improve this fitness
      component. Surprisingly, however, there has been little research about the best
      training methods to improve RSA. In the absence of strong scientific evidence,
      two principal training theories have emerged. One is based on the concept of
      training specificity and maintains that the best way to train RSA is to perform
      repeated sprints. The second proposes that training interventions that target the
      main factors limiting RSA may be a more effective approach. The aim of this
      review (Part II) is to critically analyse training strategies to improve both RSA
      and the underlying factors responsible for fatigue during repeated sprints (see
      Part I of the preceding companion article). This review has highlighted that
      there is not one type of training that can be recommended to best improve RSA and
      all of the factors believed to be responsible for performance decrements during
      repeated-sprint tasks. This is not surprising, as RSA is a complex fitness
      component that depends on both metabolic (e.g. oxidative capacity,
      phosphocreatine recovery and H+ buffering) and neural factors (e.g. muscle
      activation and recruitment strategies) among others. While different training
      strategies can be used in order to improve each of these potential limiting
      factors, and in turn RSA, two key recommendations emerge from this review; it is
      important to include (i) some training to improve single-sprint performance (e.g.
      'traditional' sprint training and strength/power training); and (ii) some high
      intensity (80-90% maximal oxygen consumption) interval training to best improve
      the ability to recover between sprints. Further research is required to establish
      whether it is best to develop these qualities separately, or whether they can be
      developed concurrently (without interference effects). While research has
      identified a correlation between RSA and total sprint distance during soccer,
      future studies need to address whether training-induced changes in RSA also
      produce changes in match physical performance.

PMID- 21846164
TI  - Induction and decay of short-term heat acclimation in moderately and highly
      trained athletes.
AB  - A rethinking of current heat-acclimation strategies is required as most research
      and advice for improving physiological strain in the heat includes maintaining
      hydration using long-term acclimation protocols (>10 days). Furthermore, these
      strategies have tended to use untrained and moderately trained participants.
      Therefore, the aims of this review were to (i) investigate the effectiveness of
      short-term heat acclimation (STHA) with moderately and highly trained athletes;
      (ii) determine the importance of fluid regulatory strain, which has a thermally
      independent role in heat adaptation; (iii) assess the impact of STHA on a marker
      of thermotolerance (inducible heat-shock protein 70 [HSP70]); and (iv) provide
      further information on the decay of acclimation to heat. The review suggests that
      5-day STHA is effective, and adaptations may be more pronounced after fluid
      regulatory strain from a dehydration-acclimation regimen. Furthermore, highly
      trained athletes may have similar physiological gains to those who are less
      trained using STHA. However, research has tended to focus on untrained or
      moderately trained participants and more information is required for highly
      trained populations. HSP70 response is upregulated across STHA. This indicates
      increased thermotolerance and protective adaptive change that may indicate HSP70
      response as a useful marker of heat acclimation. Physiological adaptations after
      heat acclimation are relatively short term and may vanish only a few days or
      weeks after removal from heat exposure. From a practical perspective 5-day STHA
      may be the preferred acclimation regimen for moderately and highly trained
      athletes as it has been shown to be effective, less expensive and less likely to
      disrupt the tapering for competition in elite performers. Furthermore, updated
      information on the time course of acclimation decay may allow a reliable estimate
      of how long individuals can be free from heat exposure before reacclimation is
      required. This is particularly pertinent in present times as many athletes,
      civilians and military personnel increasingly have to relocate to different
      climates of the world, often within a short period of time.

PMID- 21846166
TI  - A systematic program of research regarding the assessment of speech-language
      pathology competencies.
AB  - This paper explores the nature and development of competence in speech-language
      pathology and is informed by the development and validation of a competency-based
      assessment tool to assess Australian speech-language pathology students'
      professional performance in the workplace (COMPASS). Background is provided on
      speech-language pathology competency frameworks in Australia and a systematic
      program of research to validate this assessment tool. Findings relevant to
      understanding the nature and development of speech-language pathology competency
      are described. The domains of competence considered important for practice were
      found to extend beyond specific processes of professional practice to include
      generic competencies of reasoning, communication, lifelong learning, and
      professionalism. The achievement of competency was identified as developmental,
      and clinical educators were found to validly and reliably identify seven levels
      of competency development. Competency may transfer across the scope of practice,
      and marginal students' performances were characterized by a high degree of
      variability. These findings are discussed in relation to the profession's
      understanding of competency and speech-language pathology education, professional
      development, and further research.

PMID- 21846165
TI  - Effects of acute carbohydrate supplementation on endurance performance: a meta
      analysis.
AB  - Research on the performance effects of acute carbohydrate supplementation is
      comprehensive. Here we present the first meta-analytic review of this research.
      METHODS: Eighty-eight randomized crossover studies in which carbohydrate
      supplements were consumed with or without protein before and/or during exercise
      provided 155 estimates for performance effects in time-to-exhaustion tests or in
      time trials with or without a preload. For the mixed-model meta-analysis, all
      effects were converted into percentage changes in mean power in a non-preloaded
      time trial and weighted using percentage standard errors derived from exact p
      values (in a minority of studies) or from estimated errors of measurement (in all
      other studies). Publication bias was assessed with a plot of t-values for the
      random-effect solutions versus standard errors. Probabilistic inferences were
      derived with reference to thresholds for small, moderate and large effects on
      performance of 0.5, 1.5 and 2.7%. RESULTS: Publication bias was reduced by
      excluding studies with a standard error >1.25%. In the remaining 73 studies and
      122 estimates, the meta-analysed performance effects of carbohydrate supplements
      ranged from clear large improvements of ~6% to clear moderate impairments of ~2%.
      The best supplement inferred from the analysis consisted of a ~3-10% carbohydrate
      plus-protein drink providing ~0.7 g/kg/h glucose polymers, ~0.2 g/kg/h fructose
      and ~0.2 g/kg/h protein. Substantial increases in the benefit of a supplement
      were probably small with an additional 9-hour fast and with the inclusion of ~0.2
      g/kg/h of protein, probably small to moderate with ingesting the first bolus not
      at the start of exercise but 1-4 hours before exercise, and possibly small with
      increasing the frequency of ingestion by three boluses per hour. Substantial
      reductions in the benefit of a supplement were possibly moderate with a
      supplement providing >0.25 g/kg/h fructose, and possibly small with an increase
      in ambient temperature of 10 degrees C. The effect in subjects with maximal
      oxygen consumption higher by 10 mL/kg/min was probably trivial, and the effects
      of exercise duration were dependent on the concentration of carbohydrate plus
      protein in the supplement. The effect of including salt was unexpectedly trivial,
      and the effect of gender was unclear. CONCLUSIONS: Carbohydrate supplements with
      an appropriate composition and administration regimen can have large benefits on
      endurance performance. More research and better reporting are required to
      investigate the moderating effects of gender and salt.

PMID- 21846167
TI  - Influence of L2 proficiency on kinematic duration of single words: Real and novel
      word production by Bengali-English speakers.
AB  - The study explored the influence of second language proficiency on the kinematic
      duration of single words. Participants produced real and novel words with
      variable stress targets (e.g., trochaic and iambic) embedded in first language
      (L1) and second language (L2) sentence frames. Participants were monolingual
      English speakers (n=10) and Bengali-English bilinguals with early exposure to
      English (n=10) and late exposure to English (n=10). Bengali was the L1 and
      English was the L2 for all 20 bilingual participants. Duration of lip movements
      for the target real and novel words was analysed. Results suggest that kinematic
      duration of single words was not influenced by speakers' L2 proficiency. However,
      L2 proficiency influenced foreign accent ratings for the real words, but not the
      novel words. Kinematic duration and perception of accent were not correlated,
      which might imply that accent reduction might not always be a direct consequence
      of shorter word duration.

PMID- 21846168
TI  - Adult Hearing Screening: what comes next?

PMID- 21846170
TI  - Months in space: synaesthesia modulates attention and action.
AB  - Month-space synaesthetes experience months as sequences arranged in spatially
      defined configurations. While most works on synaesthesia have studied its
      perceptual implications, this study focuses on the synaesthetic influence on a
      synaesthete's action behaviour. S.M., a month-space synaesthete, and 5 matched
      controls performed a spatial Stroop-like task in a haptics and virtual reality
      combined environment, which was especially designed to simulate S.M.'s three
      dimensional synaesthetic experience. In the experiment, a circle and a word were
      presented simultaneously. The word consisted of either a month name or a
      direction name and was located at the centre of the screen, while the circle was
      displayed in one of four peripheral positions-top, bottom, right, or left. When
      S.M. was asked to ignore the word and reach for the circle, no effects were
      found. In contrast, when she was asked to ignore the circle and reach for a
      location indicated by the word, a congruency effect was found for both months and
      direction words. Crucially, these effects were evident in all measurements of
      reaching performance (i.e., path, velocity, and trajectory of movement). Our
      findings revealed that for month-space synaesthetes, months trigger spatial
      shifts of attention in a similar manner as directions do. Moreover, these shifts
      of attention affected not only latent cognitive processes (i.e., reaction time)
      but also overt behaviour (i.e., entire hand movements).

PMID- 21846171
TI  - Antidiarrheal mechanism of Carpolobia lutea leaf fractions in rats.
AB  - CONTEXT: Carpolobia lutea G. Don (Polygalaceae) leaf is reputable as an
      antidiarrheal agent among the Efik and Ibibio tribe of Akwa Ibom State, Nigeria.
      The crude extract is reported to show antidiarrheal and antiulcer effects in
      rodents. OBJECTIVE: The isolation and characterization of drug molecules from the
      leaf fraction with antidiarrheal bioactivity and determination of mechanism of
      action are reported. MATERIAL AND METHODS: Gradient extraction by maceration
      yielding n-hexane, chloroform, ethyl acetate, and ethanol fractions (770 mg/kg)
      were used to establish the fractions suitable for drug discovery. The
      antidiarrheal effect of the leaf fractions of Carpolobia lutea was evaluated
      using castor oil-induced diarrhea, castor oil-induced intestinal transit, and
      enteropooling. RESULTS: Results indicate that all fractions produced a
      significant (p < 0.01-0.001) decrease in castor oil-induced diarrhea in rats.
      This effect was not antagonized by isosorbide dinitrate (150 mg/kg, p.o),
      diphenoxylate (5 * 10-3 mg/kg p.o) and yohimbine (1 mg/kg, s.c.) except for the
      chloroform fraction. The ethyl acetate fraction produced 100% inhibition of
      intestinal transit, an effect greater than pure drug. Phytochemical analysis of
      the ethyl acetate fraction yielded polyphenolic compounds. CONCLUSION: The leaf
      fractions contain two types of antidiarrheal agents, one mediating its effect
      through alpha1-presynaptic adrenoceptor while the other does not. Polyphenols
      isolated may in part lend credence for observed antidiarrheal activity.

PMID- 21846172
TI  - Cytotoxic and antioxidant activities of selected Lamiales species from Mexico.
AB  - CONTEXT: Methanol extracts obtained from eight species belonging to four families
      of the Lamiales order native to Mexico were investigated for biological action.
      OBJECTIVE: Cytotoxicity and antioxidant activity of methanol extracts have been
      investigated. MATERIALS AND METHODS: Cytotoxic activity was evaluated by the
      sulphorhodamine B protein staining assay against KB (nasopharyngeal), HEp-2
      (larynx), HF-6 (colon), MCF7 (breast), PC-3 (prostate), and Ca Ski (cervix)
      carcinoma cell lines. To analyze the antioxidant activity, common stable radicals
      chromogens, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS+) and DPPH
      (1,1-diphenyl-2-picrylhydrazyl) were used. The ferric reducing antioxidant power
      (FRAP) and the total phenolic content of the samples were also determined.
      RESULTS: Some of the extracts, such as Limosella aquatica L. (Scrophulariaceae),
      Mimulus glabratus Kunth. (Phrymaceae), Pedicularis mexicana Zucc. ex Benth.
      (Orobanchaceae), and Penstemon campanulatus (Cav.) Willd. (Plantaginaceae)
      displayed remarkably selective cytotoxic activity. However, the extract from
      Veronica americana (Raf.) Schwein (Plantaginaceae) showed the highest activity
      with IC50 values of 1.46 and 0.169 g/ MUL on PC-3 and HF-6 cells, respectively.
      With the exception of M. glabratus, all the extracts showed different degrees of
      antioxidant activity with IC50 values from 0.89 up to 1.8 in the ABTS assay; from
      0.49 up to 1.25 mg/mL in the DPPH assay and with the FRAP evaluation, 36 to 68
      equivalents in mM of FeSO4. V. americana also showed the highest antoxidant
      activity with IC50 values from 0.491 and 0.892 mg/mL, on DPPH and ABTS assays,
      respectively. DISCUSSION AND CONCLUSION: These findings demonstrated that the
      species studied have great potential cytotoxic and antioxidant activity.

PMID- 21846173
TI  - Nootropic, anxiolytic and CNS-depressant studies on different plant sources of
      shankhpushpi.
AB  - CONTEXT: Shankhpushpi, a well-known drug in Ayurveda, is extensively used for
      different central nervous system (CNS) effects especially memory enhancement.
      Different plants are used under the name shankhpushpi in different regions of
      India, leading to an uncertainty regarding its true source. Plants commonly used
      under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus
      alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn.
      (Leguminosae). OBJECTIVE: To find out the true source of shankhpushpi by
      evaluating and comparing memory-enhancing activity of the three above mentioned
      plants. Anxiolytic, antidepressant and CNS-depressant activities of these three
      plants were also compared and evaluated. MATERIALS AND METHODS: The nootropic
      activity of the aqueous methanol extract of each plant was tested using elevated
      plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS
      depressant studies were evaluated using EPM, Porsolt?s swim despair and
      actophotometer models, respectively. RESULTS: C. pluricaulis extract (CPE) at a
      dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p <
      0.001). E. alsinoides extract (EAE) and C. ternatea extract (CTE) showed maximum
      memory-enhancing and anxiolytic activity (p < 0.001) at 200 and 100?mg/kg,
      respectively. Amongst the three plants, EAE and CTE showed significant (p <
      0.05), while CPE did not exhibit any antidepressant activity. All the three
      plants showed CNS-depressant action at higher dose levels. DISCUSSION AND
      CONCLUSIONS: The above results showed all the three plants possess nootropic,
      anxiolytic and CNS-depressant activity. The results of memory-enhancing activity
      suggest C. pluricaulis to be used as true source of shankhpushpi.

PMID- 21846174
TI  - Aqueous extract of Boerhaavia diffusa root ameliorates ethylene glycol-induced
      hyperoxaluric oxidative stress and renal injury in rat kidney.
AB  - INTRODUCTION: Boerhaavia diffusa Linn. (Nyctaginaceae) is widely used in
      traditional Indian medicines against renal afflictions including calcium oxalate
      (CaOx) urolithiasis and is known for antioxidant activity. OBJECTIVE: The present
      study was designed to investigate the ameliorating effect of aqueous extract of
      B. diffusa roots (BDE) in hyperoxaluric oxidative stress and renal cell injury.
      MATERIAL AND METHODS: In vitro antioxidant activity of BDE was estimated in terms
      of total phenolic content and 1,1-diphenyl-2-picryl hydrazyl free radical
      scavenging activity. Wistar albino rats were given 0.75% v/v ethylene glycol in
      drinking water to induce chronic hyperoxaluria and simultaneously BDE was given
      to nephrolithiasic treated rats at the dose of 100 and 200 mg/kg b.w. orally for
      28 days. Urinary volume, oxalate, serum creatinine, blood urea nitrogen (BUN),
      malondialdehyde (MDA) and antioxidant enzyme (SOD, CAT, GST, GPx) were evaluated.
      RESULTS AND DISCUSSION: BDE extract was found to posses a high total phenolic
      content and exhibited significant free radicals scavenging activity. Oxalate
      excretion significantly increased in hyperoxaluric animals as compared to control
      which was protected in BDE-treated animals. BDE treatment significantly reduced
      level of MDA and improved the activity of antioxidant enzymes followed by
      reduction in BUN and serum creatinine. In addition, BDE reduced the number of
      CaOx monohydrate crystals in the urine. Histological analysis depicted that BDE
      treatment inhibited deposition of CaOx crystal and renal cell damage. CONCLUSION:
      The present study reveals that antioxidant activity of BDE significantly protects
      against hyperoxaluric oxidative stress and renal cell injury in urolithiasis.

PMID- 21846175
TI  - Drug monitoring of a case of citalopram overdosage.
AB  - Selective serotonin reuptake inhibitors are widely prescribed drugs without
      recognized cardiovascular risk. We report the case of a 54-year-old patient who
      developed QTc interval prolongation, followed by ventricular fibrillation
      episodes, 10 hours after admission to the ICU, in the setting of a citalopram
      overdose. Citalopram plasma values dropped from 5.88 to 0.34 mg/L at 9 days
      postadmission. The patient was treated by oral activated charcoal, and final
      outcome was favorable.

PMID- 21846176
TI  - The extent of food advertising to children on UK television in 2008.
AB  - OBJECTIVE: To provide the most comprehensive analysis to date of the extent of
      food advertising on UK television channels popular with young people following
      regulatory reform of this type of marketing activity. METHODS: UK television was
      recorded 06:00-22:00 h for a weekday and a weekend day every month between
      January and December 2008 for 14 of the most popular commercial channels
      broadcasting children's/family viewing. Recordings were screened for
      advertisements, which were coded according to predefined categories including
      whether they were broadcast in peak/non-peak children's viewing time. Food
      advertisements were coded as core (healthy)/non-core (unhealthy)/miscellaneous
      foods. RESULTS: Food and drinks were the third most heavily advertised product
      category, and there were a significantly greater proportion of advertisements for
      food/drinks during peak compared to non-peak children's viewing times. A
      significantly greater proportion of the advertisements broadcast around soap
      operas than around children's programmes were for food/drinks. Children's
      channels broadcast a significantly greater proportion of non-core food
      advertisements than the family channels. There were significant differences
      between recording months for the proportion of core/non-core/miscellaneous food
      advertisements. CONCLUSIONS: Despite regulation, children in the UK are exposed
      to more TV advertising for unhealthy than healthy food items, even at peak
      children's viewing times. There remains scope to strengthen the rules regarding
      advertising of HFSS foods around programming popular with children and adults
      alike, where current regulations do not apply. Ongoing, systematic monitoring is
      essential for evaluation of the effectiveness of regulations designed to reduce
      children's exposure to HFSS food advertising on television in the UK.

PMID- 21846177
TI  - NPR-C protects embryonic stem cells from apoptosis by regulating p53 levels.
AB  - The identification of intrinsic factors required for propagation of self-renewing
      embryonic stem (ES) cells is important to improve the efficiency of expansion of
      ES cells for therapeutic purposes. Here, we report a novel role for natriuretic
      peptide receptor-C (NPR-C) in the survival of murine ES cells. We found that NPR
      C was highly expressed in ES cells and was downregulated during ES cell
      differentiation. Knockdown of NPR-C in ES cells by using a small-interfering RNA
      resulted in apoptotic cell death, and the induction of p53 protein expression.
      Conversely, chemical inhibition of p53 by alpha-pifithrin significantly reduced
      apoptosis in NPR-C-deficient cells. cANF((4-23)), a selective NPR-C agonist,
      protected ES cells against oxidative stress-induced apoptosis, and blocked
      activation of p53 and Nanog suppression in the presence of DNA-damaging agents.
      Thus, NPR-C is required to control DNA damage-induced p53 levels to maintain ES
      cell self-renewal.

PMID- 21846178
TI  - Fetal cells in the murine maternal lung have well-defined characteristics and are
      preferentially located in alveolar septum.
AB  - The transfer of fetal cells to maternal organs occurs in mouse and human
      pregnancy. Techniques such as polymerase chain reaction and flow cytometry do not
      permit study of fetal cell morphology or anatomic location. Using a green
      fluorescent protein (GFP) transgenic mouse model, our objective was to determine
      whether GFP+ signal emanates from intact or degraded fetal cells, and whether
      they have a characteristic appearance and location within maternal lung. Four
      wild-type female mice were mated to males homozygous for the Gfp transgene and
      studied at days e16-18. Controls were 2 females mated to wild-type males.
      Morphologic appearance and anatomic position of each GFP+ object within maternal
      lung was recorded. GFP signals were sufficiently bright to be visualized without
      anti-GFP antibody and were confirmed by confocal microscopy to be separate from
      fluorescent artifact. Of 438 GFP+ objects detected, 375 (85.6%) were from intact
      cells, and 63 (14.4%) were acellular. Four distinct categories of intact cells
      were observed. Of these, 23.2% had mononuclear morphology with a relatively large
      nucleus and GFP+ cytoplasm (Group A). An additional group of cells (10.1%) had
      mononuclear morphology and podocyte extensions (Group B). The remainder of cells
      had fragmented nuclei or cytoplasm. Both intact cells and acellular fragments
      were predominantly localized to the maternal alveolar septum (P<0.0001). This
      study demonstrates that fetal GFP+ cells are predominantly located in the
      alveolar septum and have characteristic morphologies, although it remains unclear
      whether these represent distinct categories of cells or degrading cells.
      Nevertheless, this naturally acquired population of fetal cells in maternal lung
      should be considered in studies of lung biology and repair.

PMID- 21846179
TI  - The ovarian follicular pool and reproductive outcome in women.
AB  - Both quantitative and qualitative aspects of the ovarian reserve are inversely
      related to age, hence the relationship existing between low quantity and low
      quality may be only indirect and depending on their strong relationship with the
      third variable, namely women's age. However the possibility exists that they may
      also be directly related. The objective of this study was to investigate the
      relationship between ovarian reserve and female reproductive outcome. Eight
      published studies reporting histological data on the human ovaries have been
      carefully reviewed. Only studies where the reproductive history of women was
      reported have been included for the analysis. The non-growing follicle count was
      plotted versus age and the best fit line through the data was calculated. All
      patients were assigned as to be above or below the calculated median hence
      differentiating women with high or low ovarian reserve for their age. A similar
      number of pregnancies ended in miscarriage in women with low and high ovarian
      reserve. The number of deliveries per woman in both the groups was not
      statistically different. The results of the study do not support the hypothesis
      that quality and quantity of the follicular pool are directly related.

PMID- 21846181
TI  - Molecular study of five Chinese patients with 46XX partial 17a-hydroxylase/17,20
      lyase deficiency.
AB  - CONTEXT: Partial 17a-hydroxylase/17,20 lyase deficiency (17OHD) is a rare subtype
      of 17OHD caused by CYP17 gene mutations. OBJECTIVE: Five Chinese 46,XX patients
      and one family with partial 17OHD were genotyped. PATIENTS: The five patients
      derived from different families and one of them had another patient in family.
      The diagnosis of partial 17OHD was established through clinical and laboratory
      characteristics in Peking Union Medical College Hospital, China, from 2000 to
      2010. RESULTS: Seven CYP17 gene mutations are identified from these patients.
      Among them, R449C and L209P are two novel missense mutations. Four patients are
      found to have a compound heterozygous mutations and one patient has only one
      mutation. The patients with family history are also found to have parent origin
      of gene mutations. CONCLUSION: Two novel missense mutations in CYP1 7 are found
      in this study. Comparing with previous reports, the different combination of
      mutations may have various effects on the activities of the 17-hydroxylase
      and/or17,20-lyase.

PMID- 21846180
TI  - 14S,21R-dihydroxy-docosahexaenoic acid treatment enhances mesenchymal stem cell
      amelioration of renal ischemia/reperfusion injury.
AB  - Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve
      treatment of renal failure. The prohealing functions of MSCs have been found to
      be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy
      docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article,
      using a murine model of renal ischemia/reperfusion (I/R) injury, we found that
      treatment with 14S,21R-diHDHA enhanced MSC amelioration of renal I/R injury.
      Treated MSCs more efficiently inhibited I/R-induced elevation of serum creatinine
      levels, reduced renal tubular cell death, and inhibited infiltration of
      neutrophils, macrophages, and dendritic cells in kidneys. Conditioned medium from
      treated MSCs reduced the generation of tumor necrosis factor-alpha and reactive
      oxygen species by macrophages under I/R conditions. Infusion of treated MSCs more
      efficiently reduced I/R-damage to renal histological structures compared with
      untreated MSCs (injury score: 7.9+/-0.4 vs. 10.5+/-0.5). Treated MSCs were
      resistant to apoptosis in vivo when transplanted under capsules of I/R-injured
      kidneys (active caspase-3+ MSCs: 4.2%+/-2.8% vs. 11.7%+/-2.4% of control) and in
      vitro when cultured under I/R conditions. Treatment with 14S,21R-diHDHA promoted
      viability of MSCs through a mechanism involving activation of the
      phosphoinositide 3-kinase -Akt signaling pathway. Additionally, treatment of MSCs
      with 14S,21R-diHDHA promoted secretion of renotrophic hepatocyte growth factor
      and insulin growth factor-1. Similar results were obtained when 14S,21RdiHDHA was
      used to inhibit apoptosis of human MSCs (hMSCs) and to increase the generation of
      renotrophic cytokines from hMSCs. These findings provide a lead for new
      strategies in the treatment of acute kidney injury with MSCs.

PMID- 21846182
TI  - Prognosis of patients with t(8;16)(p11;p13) acute myeloid leukemia.

PMID- 21846183
TI  - Antibacterial and modulatory effect of Stryphnodendron rotundifolium.
AB  - CONTEXT: Stryphnodendron rotundifolium Mart. (Leguminosae), a tree in Northeast
      Brazil (Chapada do Araripe), is used in popular medicine to treat different
      processes such as inflammation and infectious diseases, mainly caused by
      bacterial pathogens. OBJECTIVE: This study determined the modulatory and
      antimicrobial activity of the hydroethanol extract of dried stem bark, the most
      used form of this natural product, as a remedy by the traditional communities,
      against standard and clinical isolates of Escherichia coli and Staphylococcus
      aureus. MATERIAL AND METHODS: The antibacterial and modulatory activities of the
      hydroalcoholic extract from the leaves were obtained by
      maceration/hydrodistillation method and assayed by microdilution. RESULTS: In the
      microbiological assays, growth inhibition was demonstrated by this extract
      against the bacterial strains tested, with minimal inhibitory concentration (MIC)
      values of 512 MUg/mL. However, when a subinhibitory concentration (MIC/8 = 64
      MUg/mL) was combined with conventional antimicrobial drugs (gentamicin,
      kanamycin, amikacin and neomycin), the extract showed a potentiating effect,
      reducing the MIC for all drugs assayed in a range between 312.5 and 2.4 MUg/mL.
      CONCLUSIONS: We indicate that the extract of S. rotundifolium showed potential
      synergistic antibiotic activity. With the results obtained, these extracts proved
      to be a promising source of antibacterial and modulatory agents.

PMID- 21846184
TI  - Use of interim [18F]fluorodeoxyglucose-positron emission tomography is not
      justified in diffuse large B-cell lymphoma during first-line immunochemotherapy.
AB  - In diffuse large B-cell lymphoma (DLBCL), the response to first-line
      immunochemotherapy remains somewhat unpredictable. Interim
      [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) (PET-int)
      analysis could be an important tool in the prompt shift to intensified regimens.
      We prospectively evaluated the effectiveness of PET-int carried out at mid
      treatment with standard immunochemotherapy in predicting relapse in a series of
      85 consecutive patients with DLBCL. PET-int results were dichotomized as positive
      or negative using the recently validated five-point scale scoring system. This
      examination was also compared with interim computed tomography (CT-int) and final
      PET (PET-fin). End-points were: complete remission (CR), positive predictive
      value (PPV) of refractoriness and relapse, negative predictive value (NPV),
      overall survival (OS) and progression-free survival (PFS). Observation time was
      fixed to 24 months unless preceded by a DLBCL-related event. The PPV of PET-int
      was 58% and the NPV was 77%. CR was correlated with both PET-int and CT-int (p <
      0.0001), but in multivariate analysis only CT-int was correlated with CR (p =
      0.002). CT-int and PET-fin were predictive of both OS and PFS, whereas PET-int
      was predictive only of OS (p = 0.013). In Cox regression only PET-fin was
      predictive for both OS (p = 0.004) and PFS (p = 0.005). PET-int was unable to
      discriminate those chemosensitive patients who would later relapse. We therefore
      believe that the use of this expensive radioactive tool is not justified as an
      interim analysis.

PMID- 21846185
TI  - Survival of patients with hematological malignancy admitted to the intensive care
      unit: prognostic factors and outcome compared to unselected medical intensive
      care unit admissions, a parallel group study.
AB  - Improved survival in patients with hematological malignancy (HM) admitted to the
      intensive care unit (ICU) has largely been reported in uncontrolled cohorts from
      single academic institutions. We compared hospital mortality between 147 patients
      with HM and 147 general medical admissions to five non-specialist ICUs. The
      proportion of patients surviving to hospital discharge was significantly worse in
      patients with HM (27% vs. 56%; p < 0.001). Six-month and 1-year survival in
      patients with HM was 21% and 18%, respectively. HM, greater age, mechanical
      ventilation (MV) and acute physiology and chronic health evaluation (APACHE) II
      score were independent predictors of poor outcome. For patients with HM, culture
      proven infection, age, MV and inotropes were negative predictors. Disease
      specific factors including hematological diagnosis, neutropenia, remission
      status, prior stem cell transplant, time from diagnosis to admission and degree
      of prior treatment were not predictive. Overall survival of patients with HM was
      worse than that recently reported from specialist units.

PMID- 21846186
TI  - A112, a tamibarotene dimethylaminoethyl ester, may inhibit human leukemia cell
      growth more potently than tamibarotene.
AB  - A112 is a tamibarotene dimethylaminoethyl ester considered a candidate compound
      for the treatment of acute promyelocytic leukemia (APL) and acute myeloid
      leukemia (AML). Our goal in this study was to evaluate the efficacy of anti
      cancer activity, beginning by studying its inhibitory effects on leukemia cells
      and then comparing it to tamibarotene. A112 effectively inhibited the growth of
      HL-60 and NB4 cells as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The inhibitory effect of A112 was
      confirmed in mice in which A112 delayed the growth of HL-60 xenografts after 3
      weeks' injection. The efficacy of A112 on leukemia cell growth was stronger than
      that of tamibarotene at the same dosage. The detection of A112 and tamibarotene
      in plasma of rats showed that A112 might sustain release of its hydrolysate
      tamibarotene, and the concentration was maintained at a higher level and for a
      longer time than that of tamibarotene injection. We studied the differentiation
      morphologies of leukemic cells exposed to A112 or tamibarotene. The number of
      differentiated NB4 cells was increased, suggesting that A112 possessed
      differentiation activity in the inhibition of leukemia growth. Further studies
      showed that the expression of CD11b, a marker of terminal granulocyte
      differentiation, was increased as estimated by flow cytometry with a direct
      immunofluorescence assay. A112 was found to induce the activation of
      CCAAT/enhancer-binding protein beta (C/EBPbeta) and cyclin-dependent kinase (CDK)
      inhibitors p21(Waf1/cip1) and p27(Kip1) while cell growth was inhibited. These
      activities of A112 were greater than those of tamibarotene. The higher efficacy
      of A112 was also evidenced by induction of apoptosis in leukemia cells. A112
      induced a greater number of annexin V-positive cells than did tamibarotene as
      measured by flow cytometry analysis. Treatment of mice with A112 resulted in
      stronger terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      staining in HL-60 xenografts. Western blot analysis revealed that A112 increased
      the expression of caspase-3, caspase-9 and cleaved poly(ADP-ribose) polymerase
      (PARP) in leukemia cells both in vitro and in vivo, indicating that induction of
      apoptosis was involved in the inhibition of leukemia growth. Taken together,
      these results suggest that A112 is a highly effective derivative of trans
      retinoic acid and a potential candidate compound for the treatment of leukemia.

PMID- 21846187
TI  - Myelomeningocele and pregnancy: a case report and review of the literature.
AB  - The improvement of antenatal management and surgical techniques has greatly
      increased the survival rate of infants with spina bifida. More of these women are
      reaching adulthood and reproductive age and therefore could become pregnant.
      Pregnancy complications depend on the kind of spina bifida and subject's
      condition.We report a case of woman with a severe kyphoscoliosis, that
      progressively affects lung capacity until 32 weeks of gestation, when she
      underwent caesarean section.These patients deserve careful obstetric care,
      genetic counselling and urological, obstetric, neurological and anaesthetic
      management.

PMID- 21846190
TI  - Could it be advantageous to tune the temperature controller during radiofrequency
      ablation? A feasibility study using theoretical models.
AB  - PURPOSE: To assess whether tailoring the Kp and Ki values of a proportional
      integral (PI) controller during radiofrequency (RF) cardiac ablation could be
      advantageous from the point of view of the dynamic behaviour of the controller,
      in particular, whether control action could be speeded up and larger lesions
      obtained. METHODS: Theoretical models were built and solved by the finite element
      method. RF cardiac ablations were simulated with temperature controlled at 55
      degrees C. Specific PI controllers were implemented with Kp and Ki parameters
      adapted to cases with different tissue values (specific heat, thermal
      conductivity and electrical conductivity) electrode-tissue contact
      characteristics (insertion depth, cooling effect of circulating blood) and
      electrode characteristics (size, location and arrangement of the temperature
      sensor in the electrode). RESULTS: The lesion dimensions and T(max) remained
      almost unchanged when the specific PI controller was used instead of one tuned
      for the standard case: T(max) varied less than 1.9 degrees C, lesion width less
      than 0.2 mm, and lesion depth less than 0.3 mm. As expected, we did observe a
      direct logical relationship between the response time of each controller and the
      transient value of electrode temperature. CONCLUSION: The results suggest that a
      PI controller designed for a standard case (such as that described in this
      study), could offer benefits under different tissue conditions, electrode-tissue
      contact, and electrode characteristics.

PMID- 21846189
TI  - Radiofrequency ablation combined with liposomal quercetin to increase tumour
      destruction by modulation of heat shock protein production in a small animal
      model.
AB  - PURPOSE: To investigate the effect of heat shock protein (HSP) modulation on
      tumour coagulation by combining radiofrequency (RF) ablation with adjuvant
      liposomal quercetin and/or doxorubicin in a rat tumour model. METHODS: Sixty
      R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved
      study. Initially, 60 tumours (n=6, each subgroup) were randomised into five
      groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1 mg/kg),
      (3) IV liposomal quercetin followed 24 h later with RF, (4) RF followed 15 min
      later by IV liposomal doxorubicin (8 mg/kg), (5) IV liposomal quercetin 24 h
      before RF followed by IV liposomal doxorubicin 15 min post-ablation. Animals were
      sacrificed 4 or 24 h post-treatment and gross coagulation diameters were
      compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved
      caspase-3 expression. Comparisons were performed by using Student t-tests or
      ANOVA. RESULTS: Combination RF-quercetin significantly increased coagulation size
      compared with either RF or liposomal quercetin alone (13.1+/-0.7 mm vs. 8.8+/-1.2
      mm or 2.3+/-1.3 mm, respectively, P<0.001 for all comparisons). Triple therapy
      (quercetin-RF-doxorubicin) showed larger coagulation diameter (14.5+/-1.0 mm) at
      24 h than quercetin-RF (P=0.016) or RF-doxorubicin (13.2+/-1.3 mm, P=0.042).
      Combination quercetin-RF decreased Hsp70 expression compared with RF alone at
      both 4 h (percentage of stained cells/hpf 22.4+/-13.9% vs. 38.8+/-16.1%, P<0.03)
      and 24 h (45.2+/-10.5% vs. 81.1+/-3.6%, P<0.001). Quercetin-RF increased cleaved
      caspase-3 expression at both 4 h (percentage of stained cells/hpf 50.7+/-13.4%
      vs. 41.9+/-15.1%, P<0.03) and 24 h (37.4+/-7.8% vs. 33.2+/-6.5%, P=0.045); with,
      triple therapy (quercetin-RF-doxorubicin) resulting in the highest levels of
      apoptosis (45.1+/-10.7%) at 24 h. Similar trends were observed for rim thickness.
      CONCLUSIONS: Suppression of HSP production using adjuvant liposomal quercetin can
      increase apoptosis and improve RF ablation-induced tumour destruction. Further
      increases in tumour coagulation can be seen including an additional anti-tumour
      adjuvant agent such as liposomal doxorubicin.

PMID- 21846191
TI  - CT-guided radiofrequency ablation prolonged metastatic survival in patients with
      liver metastases from nasopharyngeal carcinoma.
AB  - PURPOSE: The aim of this retrospective study was to evaluate the technical
      efficacy and survival following CT-guided radiofrequency ablation (RFA) of liver
      metastases (LM) from nasopharyngeal carcinoma (NPC) and to determine prognostic
      factors. MATERIALS AND METHODS: Between 2000 and 2008, 376 patients with LM from
      NPC were identified. Of these 17 patients with 31 LM from NPC underwent CT-guided
      percutaneous RFA. We assessed the technical effectiveness, complications and
      prognostic value of LM characteristics including timing (synchronous versus
      metachronous), number, size, presence of extra hepatic metastases and treatment
      regimen. Survival rates were calculated using the Kaplan-Meier method. RESULTS:
      Technical success was achieved in 30/31 metastases (96.7%). The median overall
      survival was 16.5 months from the time of diagnosis of LM for all the 376 NPC
      patients with LM, and 48.1 months for the 17 NPC patients with LM who received
      RFA treatment. Of the 376 patients, 111 had 1-3 LM who did not receive RFA
      treatment, with a median survival of 25.9 months compared to 48.1 months for the
      14 patients with 1-3 LM who received RFA. CONCLUSION: CT-guided RFA of LM from
      NPC can be performed with a high degree of technical effectiveness and offers the
      promise of improved survival in selected patients.

PMID- 21846192
TI  - Effects of magnetic induction hyperthermia and radiotherapy alone or combined on
      a murine 4T1 metastatic breast cancer model.
AB  - PURPOSE: The purpose of this study was to explore the effects of MIH and
      radiotherapy alone or combined on metastatic breast cancer and the underlying
      mechanisms. MATERIALS AND METHODS: A murine 4T1 metastatic breast cancer model
      was established and randomly assigned into four treatment groups: C (control), R
      (radiotherapy), MIH, and MIH+R. Tumour volume, lung metastasis, the expression of
      Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were
      evaluated. RESULTS: Group MIH + R showed significantly reduced tumour volume,
      lung metastasis, improved survival and increased Bax expression compared to group
      R or MIH (P<0.05). MMP-9 expression in the primary tumour tissue was
      significantly increased in group R compared to the other groups (P<0.05), which
      could be brought down by combined MIH treatment. Group MIH +R showed
      significantly higher CD4(+) T cell percentage as well as CD4(+)/CD8(+) cell ratio
      than group R (P<0.05). Group MIH+R showed significantly higher serum levels of
      TNF-alpha, IFN-gamma and IL-2 than group R (P<0.05). CONCLUSIONS: MIH not only
      promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell
      death, but also improves cellular immunity in mice under radiotherapy and
      decreases the potential of radiotherapy to enhance MMP-9 expression, which leads
      to significant improvement in lung metastasis and overall survival of mice under
      combined treatment of MIH and R. This study is the first to have explored the
      effect of combined hyperthermia and radiotherapy on tumour metastasis and the
      underlying mechanisms. It provides insights into the application of MIH as an
      adjuvant to radiotherapy for metastatic breast cancer.

PMID- 21846193
TI  - Hyperthermia protects mice against chronic unpredictable stress-induced anxiety
      like behaviour and hippocampal CA3 cell apoptosis.
AB  - PURPOSE: It is widely accepted that chronic stress can induce anxiety; however,
      the cellular and molecular mechanisms of stress-induced anxiety are far from
      being elucidated. Hyperthermia has been shown to induce expression of heat shock
      proteins (HSPs) to provide protection against a variety of stresses. To our
      knowledge, the effect of hyperthermia on the development of chronic unpredictable
      stress (CUS)-induced anxiety has not been studied. This study was to determine
      the relationship between hyperthermia induced Hsp72 and CUS related anxiety.
      MATERIALS AND METHODS: Heat shock factor 1 knockout (hsf1(-/-)) and wild-type
      (hsf1(+/+)) mice were subjected to CUS with or without hyperthermia treatment.
      Anxiety-like behaviours were evaluated by elevated plus maze and open field
      tests. Apoptosis in the hippocampal CA3 area was detected by TUNEL staining.
      Hsp72 protein level in the hippocampus was measured by Western blot. RESULTS: CUS
      caused significant apoptosis in hippocampal CA3 cells in both hsf1(-/-) and
      hsf1(+/+) mice, which significantly correlated with anxiety-like behaviours.
      Hyperthermia induced Hsp72 expression in hsf1(+/+) mice, but not in hsf1(-/-)
      mice. Importantly, hyperthermia protected hsf1(+/+) mice against developing CUS
      related anxiety-like behaviours and reduced CUS-induced apoptosis in hippocampal
      CA3 cells. In contrast, hyperthermia exhibited no protective role in hsf1(-/-)
      mice. CONCLUSIONS: Apoptosis of hippocampal CA3 cells is involved in the
      development of anxiety-like behaviours underlying CUS. Hsp72 protein is a crucial
      player in the protective effect of hyperthermia against CUS-induced apoptosis and
      development of anxiety-like behaviours. Our study suggests hyperthermia is an
      effective treatment for CUS-induced mood disorders.

PMID- 21846194
TI  - The critical limiting temperature and selective brain cooling: neuroprotection
      during exercise?
AB  - There is wide consensus that long duration exercise in the heat is impaired
      compared with cooler conditions. A common observation when examining exercise
      tolerance in the heat in laboratory studies is the critical limiting core
      temperature (CLT) and the apparent attenuation in central nervous system (CNS)
      drive leading to premature fatigue. Selective brain cooling (SBC) purportedly
      confers neuroprotection during exercise heat stress by attenuating the increase
      in brain temperature. As the CLT is dependent on heating to invoke a reduction in
      efferent drive, it is thus not compatible with SBC which supposedly attenuates
      the rise in brain temperature. Therefore, the CLT and SBC hypotheses cannot be
      complimentary if the goal is to confer neuroprotection from thermal insult as it
      is counter-intuitive to selectively cool the brain if the purpose of rising brain
      temperature is to down-regulate skeletal muscle recruitment. This presents a
      circular model for which there is no apparent end to the ultimate physiological
      outcome; a 'hot brain' selectively cooled in order to reduce the CNS drive to
      skeletal muscle. This review will examine the postulates of the CLT and SBC with
      their relationship to the avoidance of a 'hot brain' which together argue for a
      theoretical position against neuroprotection as the key physiological strategy in
      exercise-induced hyperthermia.

PMID- 21846195
TI  - Mild hyperthermia enhances human monocyte-derived dendritic cell functions and
      offers potential for applications in vaccination strategies.
AB  - Dendritic cell (DC)-based immunotherapy has been shown to be a promising strategy
      for anti-cancer therapy. Nevertheless, only a low overall clinical response rate
      has been observed in vaccinated patients with advanced cancer and therefore
      methods to improve DC immuno-stimulatory functions are currently under intense
      investigation. In this respect, we exposed human monocyte-derived DCs to a
      physiological temperature stress of 40 degrees C for up to 24 h followed by
      analysis for (i) expression of different heat shock proteins, (ii) survival,
      (iii) cell surface maturation markers, (iv) cytokine secretion, and (v) migratory
      capacity. Furthermore, we examined the ability of heat-shocked DCs to prime naive
      CD8(+) T cells after loading with MelanA peptide, by transfection with MelanA
      RNA, or by transduction with MelanA by an adenovirus vector. The results clearly
      indicate that in comparison to control DCs, which remained at 37 degrees C, heat
      treated cells revealed no differences concerning the survival rate or their
      migratory capacity. However, DCs exposed to thermal stress showed a time
      dependent enhanced expression of the immune-chaperone heat shock protein 70A and
      both an up-regulation of co-stimulatory molecules such as CD80, CD83, and CD86
      and of the inflammatory cytokine TNF-alpha. Moreover, these cells had a markedly
      improved capacity to prime autologous naive CD8(+) T cells in vitro in an antigen
      specific manner, independent of the method of antigen-loading. Thus, our strategy
      of heat treatment of DCs offers a promising means to improve DC functions during
      immune activation which, as a physical method, facilitates straight-forward
      applications in clinical DC vaccination protocols.

PMID- 21846196
TI  - Induction of a tumour-specific CTL response by exosomes isolated from heat
      treated malignant ascites of gastric cancer patients.
AB  - PURPOSE: Tumour cell-derived exosomes may represent a novel type of cancer
      vaccine. However, the immunogenicity of exosomes derived from tumour cells has
      been shown to be poor. Therefore, in this study, exosome immunogenicity following
      heat treatment of exosomes from malignant ascites obtained from gastric cancer
      patients was evaluated. MATERIALS AND METHODS: Tumour-derived exosomes were
      isolated from heat-treated and untreated malignant ascites of gastric cancer
      patients using serial centrifugation and sucrose gradient ultracentrifugation.
      Next, in vitro experiments were performed to investigate the influence of heat
      treatment on exosome immunogenicity. RESULTS: Exosomes from heat-treated
      malignant ascites of gastric cancer patients (HS exosomes) were found to contain
      higher concentrations of heat shock proteins, Hsp70 and Hsp60, than exosomes
      derived from untreated malignant ascites obtained from gastric cancer patients.
      Additional in vitro studies suggest that exosomes derived from heat-treated
      malignant ascites are able to promote dendritic cell (DC) maturation and induce a
      tumour-specific cytotoxic T lymphocyte (CTL) response. CONCLUSIONS: Overall,
      these results demonstrate that exposure to heat stress can improve the
      immunogenicity of exosomes obtained from malignant ascites of gastric cancer
      patients.

PMID- 21846197
TI  - A feasibility study for non-invasive thermometry using non-linear ultrasound.
AB  - PURPOSE: High intensity focused ultrasound (HIFU) is used during hyperthermia
      cancer treatment to increase the tumour temperature. For an adequate and safe
      application it is important to measure the temperature in the heated region,
      preferably in a non-invasive manner and by the same modality as used for heating.
      The goal of this feasibility study is two-fold; first, it is investigated whether
      the acoustic non-linearity parameter B/A is most suitable for measuring
      temperature changes, second, a non-invasive thermometry method based on B/A is
      proposed and demonstrated. MATERIAL AND METHODS: Water is used to confirm that
      B/A is a sensitive acoustic medium parameter that is practically applicable for
      non-invasive thermometry. Next, a thermometry method is proposed that employs the
      ratios between the fundamental and the higher harmonic frequency components of a
      non-linear acoustic wave. The method determines these ratios for a measured
      acoustic pulse that has traversed a certain medium, and compares these with
      temperature dependent reference ratios for the same medium. The method is
      demonstrated using simulated measurements of an acoustic plane wave propagating
      in glycerol. RESULTS: Results obtained for water show that B/A is more sensitive
      for temperature changes than other practical acoustic parameters. For a
      combination of 16 simulated measurements, it is demonstrated that temperature can
      be predicted non-invasively with zero bias and a standard deviation of 2 degrees
      C if the noise level does not exceed -40 dB. CONCLUSION: The suitability of B/A
      as a basis for non-invasive thermometry is confirmed, and a non-invasive
      thermometry method based on B/A is proposed and successfully demonstrated.

PMID- 21846198
TI  - Efficacy of microwave hyperthermia and chemotherapy in the presence of gold
      nanoparticles: an in vitro study on osteosarcoma.
AB  - OBJECTIVE: Hyperthermia, generated using microwave (MW), infrared, ultrasound and
      other methods, is often utilised as an adjuvant technique to sensitise cancer
      lesions to radiation therapy and chemotherapy. In the current research, MW
      hyperthermia efficacy in synergism with chemotherapy was investigated in the
      presence and absence of gold nanoparticles (GNPs). MATERIALS AND METHODS: Saos-2
      cell line derived from human osteogenic sarcoma was used in the study. Various
      experiments were performed on the cells in the presence of doxorubicin and GNPs
      with MW hyperthermia. All required control groups were also considered. The in
      vitro experiments were conducted for GNPs of 20 and 40 nm, each at two
      concentrations of 13.2 and 26.4 ug/mL. After 48 hours, MTT assay was performed in
      order to evaluate the effectiveness of therapeutic parameters on cell survival.
      RESULTS: In groups with GNP-incubated cells, the cell survival was more than 95%.
      After chemotherapy, survival was determined as 37.1% and 62.8% with and without
      40 nm GNPs, respectively. Following the combined treatment of hyperthermia and
      chemotherapy, survival declined to 17% and 4.1% in the presence of 20 and 40 nm
      GNPs, respectively. GNPs of 40 nm diameter and 26.4 ug/mL concentration showed
      the highest synergistic effect on MW hyperthermia, combination of MW hyperthermia
      and chemotherapy, and chemotherapy, respectively. Dox with 40 nm GNPs had a
      higher cell destruction rate in comparison to chemotherapy alone. CONCLUSION:
      Although no cytotoxicity was observed from GNP incubation alone, their presence
      along with MW led to a decrease in survival rate, such that the lethal effects of
      MW hyperthermia with GNPs were comparable with that of doxorubicin. All combined
      treatments in the presence of 40 nm GNPs produced a higher efficiency in
      comparison to similar groups without GNPs and with 20 nm GNPs.

PMID- 21846199
TI  - Hypolipidemic effects of different angiocarp parts of Alpinia zerumbet.
AB  - CONTEXT: In utilization of Alpinia zerumbet (Pers.) Burtt and Smith
      (Zingiberaceae) (AZ), usually the angiocarps are discarded without further use.
      OBJECTIVE: We speculate whether the angiocarps could show hypolipidemic effect.
      METHODS AND METHODS: Several diets were prepared: Alpinia seed powder (ASP);
      Alpinia seed powder/husk (ASH): 40/60; and Alpinia seed essential oil (ASO): 0.01
      0.10%. Sprague-Dawley rats divided into 11 groups were fed these diets for 8
      weeks and tested for the hypolipidemic bioactivity. RESULTS: The fecal neutral
      cholesterol excretion was increased, and the serum total triglyceride (TG) was
      significantly reduced from 153.7 mg/dL in the high-fat group (H) to 114.3-119.8
      mg/dL by ASO; to 116.3-147.9 mg/dL by ASP; and to 116.2-145.3 mg/dL by ASH.
      Activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were
      almost unaffected. The high-density lipoprotein (HDL) levels were mostly raised
      by ASO to 180.3-200.8 mg/dL. The lowdensity lipoprotein (LDL) levels were mostly
      reduced to 66.8-82.6 mg/dL by ASH. The level of arachidonic acid was mostly
      raised to 0.50-0.60% by ASO, compared with 0.37% of group H. More importantly,
      the significant reduction in hepatic TG and total cholesterol (TC) implicated a
      crucial liver protective effect. DISCUSSION AND CONCLUSION: ASP and ASH consisted
      of high crude-fiber content, while ASO consisted of seed essential oil. Both the
      seed essential oil and the whole powder of AZ previously had been reported to
      possess potent hypolipidemic bioactivity. Conclusively, the hypolipidemic effect
      can be attributed to the combined effect of the essential oil and the crude
      fiber.

PMID- 21846200
TI  - Regulatory and ethical issues for phase I in utero gene transfer studies.
AB  - Clinical gene transfer research has involved adult and child subjects, and it is
      expected that gene transfer in fetal subjects will occur in the future. Some
      genetic diseases have serious adverse effects on the fetus before birth, and
      there is hope that prenatal gene therapy could prevent such disease progression.
      Research in animal models of prenatal gene transfer is actively being pursued.
      The prospect of human phase I in utero gene transfer studies raises important
      regulatory and ethical issues. One issue not previously addressed arises in
      applying U.S. research regulations to such studies. Specifically, current
      regulations state that research involving greater than minimal risk to the fetus
      and no prospect of direct benefit to the fetus or pregnant woman is not
      permitted. Phase I studies will involve interventions such as needle insertions
      through the uterus, which carry risks to the fetus including spontaneous abortion
      and preterm birth. It is possible that these risks will be regarded as exceeding
      minimal. Also, some regard the probability of therapeutic benefit in phase I
      studies to be so low that these studies do not satisfy the regulatory requirement
      that they "hold out the prospect of direct benefit" to subjects. On the basis of
      these considerations, investigators and institutional review boards might
      reasonably conclude that some phase I in utero studies are not to be permitted.
      This paper identifies considerations that are relevant to such judgments and
      explores ethically acceptable ways in which phase I studies can be designed so
      that they are permitted by the regulations.

PMID- 21846201
TI  - In vivo and in vitro pharmacological activity of Aristolochia tagala (syn:
      Aristolochia acuminata) root extracts.
AB  - CONTEXT: Aristolochia tagala Cham. (syn: Aristolochia acuminata Lam.)
      (Aristolochiaceae), known as Nallayishwari in Telugu, has been of interest to
      researchers because of its traditional uses for treating rheumatic pains and
      fever. OBJECTIVE: The anti-inflammatory activity of the petroleum ether, ethyl
      acetate, and ethanol extracts of A. tagala roots were investigated for the first
      time. MATERIALS AND METHODS: In vivo and in vitro anti-inflammatory effects were
      investigated employing the carrageenan-induced hind paw edema in rats and the
      macrophage cell line RAW264.7 stimulated with proinflammatory stimuli
      (lipopolysaccharide interferon gamma or the calcium ionophore A23187) to
      determine PGE(2) or LTB(4) release, respectively. RESULTS: All the extracts
      exhibited anti-inflammatory effects which were found to be significant (p <
      0.001) at 200 and 400 mg/kg, p.o, in rats tested and the ethyl acetate extract
      inhibited the induction of PGE(2) with IC(50) = 39.1 mg mL(-1) and LTB(4) with
      IC(50) = 29.5 mg mL(-1). DISCUSSION AND CONCLUSION: These findings demonstrate
      that the A. tagala roots have excellent anti-inflammatory activity and validate
      the traditional indications of this plant in its origin country.

PMID- 21846203
TI  - Synthesis and characterization of novel dioxoacridine sulfonamide derivatives as
      new carbonic anhydrase inhibitors.
AB  - Novel dioxoacridine sulfonamide compounds were synthesized from reaction of
      cyclic 1,3-diketones, sulfanilamide (4-amino benzene sulfonamide) and aromatic
      aldehydes. The structures of these compounds were confirmed by using spectral
      analysis (IR, H-NMR, (13)C-NMR, and mass). Human carbonic anhydrase isoenzymes
      (hCA I and hCA II) were purified from erythrocyte cells by affinity
      chromatography. The inhibitory effects of sulfanilamide, acetazolamide (AAZ), and
      newly synthesized sulfonamides on hydratase and esterase activities of these
      isoenzymes have been studied in vitro. The IC(50) values of compounds for
      esterase activity are 0.71-0.11 uM for hCA I and 0.45-0.12 uM for hCA II,
      respectively. The K(i) values of these inhibitors were determined as 0,38-0,008
      uM for hCA I and 0,19-0,001 uM for hCA II, respectively.

PMID- 21846204
TI  - Paternal genetic history of the Basque population of Spain.
AB  - This study examines the genetic variation in Basque Y chromosome lineages using
      data on 12 Y-short tandem repeat (STR) loci in a sample of 158 males from four
      Basque provinces of Spain (Alava, Vizcaya, Guipuzcoa, and Navarre). As reported
      in previous studies, the Basques are characterized by high frequencies of
      haplogroup R1b (83%). AMOVA analysis demonstrates genetic homogeneity, with a
      small but significant amount of genetic structure between provinces (Y-short
      tandem repeat loci STRs: 1.71%, p = 0.0369). Gene and haplotype diversity levels
      in the Basque population are on the low end of the European distribution (gene
      diversity: 0.4268; haplotype diversity: 0.9421). Post-Neolithic contribution to
      the paternal Basque gene pool was estimated by measuring the proportion of those
      haplogroups with a Time to Most Recent Common Ancestor (TMRCA) previously dated
      either prior (R1b, I2a2) or subsequent to (E1b1b, G2a, J2a) the Neolithic. Based
      on these estimates, the Basque provinces show varying degrees of post-Neolithic
      contribution in the paternal lineages (10.9% in the combined sample).

PMID- 21846205
TI  - Genomic evidence for an African expansion of anatomically modern humans by a
      Southern route.
AB  - There is general agreement among scientists about a recent (less than 200,000 yrs
      ago) African origin of anatomically modern humans, whereas there is still
      uncertainty about whether, and to what extent, they admixed with archaic
      populations, which thus may have contributed to the modern populations' gene
      pools. Data on cranial morphology have been interpreted as suggesting that,
      before the main expansion from Africa through the Near East, anatomically modern
      humans may also have taken a Southern route from the Horn of Africa through the
      Arabian peninsula to India, Melanesia and Australia, about 100,000 yrs ago. This
      view was recently supported by archaeological findings demonstrating human
      presence in Eastern Arabia >90,000 yrs ago. In this study we analyzed genetic
      variation at 111,197 nuclear SNPs in nine populations (Kurumba, Chenchu, Kamsali,
      Madiga, Mala, Irula, Dalit, Chinese, Japanese), chosen because their genealogical
      relationships are expected to differ under the alternative models of expansion
      (single vs. multiple dispersals). We calculated correlations between genomic
      distances, and geographic distances estimated under the alternative assumptions
      of a single dispersal, or multiple dispersals, and found a significantly stronger
      association for the multiple dispersal model. If confirmed, this result would
      cast doubts on the possibility that some non-African populations (i.e., those
      whose ancestors expanded through the Southern route) may have had any contacts
      with Neandertals.

PMID- 21846206
TI  - Geographic patterns of craniofacial variation in pre-Hispanic populations from
      the Southern Cone of South America.
AB  - In this study we analyzed the relationships and patterns of spatial variation
      from morphological cranial variability of 17 population samples representing the
      ancient inhabitants of the central territory of Argentina (archaeologically known
      as "Sierras Centrales") and other pre-Hispanic populations from different
      ecological and geographic regions of the Southern Cone of South America
      (Argentina and Uruguay), based on the analysis of 10 craniofacial measurements.
      Results obtained from D2 distances can be interpreted as evidence of a similar
      biological history for the populations that inhabited the Sierras Centrales and
      the population of Santiago del Estero. Matrix correlation analysis demonstrated
      that craniometric variation is significantly influenced by geography, suggesting
      that populations that lived at lower geographical distance share more biological
      similarity. Global spatial autocorrelation analysis suggests a clinal pattern for
      the biological variation, although Moran's I estimates calculated for each
      variable demonstrate that only nasal height and breadth show this spatial pattern
      of variation. Results from spatial regression techniques show a significant
      effect of altitude modeling nasal shape, in agreement with previous studies
      suggesting that nasal morphology is strongly influenced by environment variables.

PMID- 21846207
TI  - Migration in Afro-Brazilian rural communities: crossing demographic and genetic
      data.
AB  - Many studies have used genetic markers to understand global migration patterns of
      our species. However, there are only few studies of human migration on a local
      scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural
      communities, using demographic data and ten Ancestry Informative Markers. In
      addition to the description of migration and marriage structures, we carried out
      genetic comparisons between the three populations, as well as between locals and
      migrants from each community. Genetic admixture analyses were conducted according
      to the gene-identity method, with Sub-Saharan Africans, Amerindians, and
      Europeans as parental populations. The three analyzed Afro-Brazilian rural
      communities consisted of 16% to 30% of migrants, most of them women. The age
      pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While
      endogamous marriages predominated, exogamous marriages were mainly patrilocal.
      Migration dynamics are apparently associated with matrimonial customs and other
      social practices of such communities. The impact of migration upon the
      populations' genetic composition was low but showed an increase in European
      alleles with a concomitant decrease in the Amerindian contribution. Admixture
      analysis evidenced a higher African contribution to the gene pool of the studied
      populations, followed by the contribution of Europeans and Amerindians,
      respectively.

PMID- 21846208
TI  - Sex distribution of offspring-parents obesity: Angel's hypothesis revisited.
AB  - This study, which is based on two cross sectional surveys' data, aims to
      establish any effect of parental obesity sex distribution of offspring and to
      replicate the results that led to the hypothesis that obesity may be associated
      with sex-linked recessive lethal gene. A representative sample of 4,064 couples
      living in Renfrew/Paisley, Scotland was surveyed 1972-1976. A total of 2,338
      offspring from 1,477 of the couples screened in 1972-1976, living in Paisley,
      were surveyed in 1996. In this study, males represented 47.7% among the total
      offspring of the couples screened in 1972-1976. In the first survey there was a
      higher male proportion of offspring (53%, p < 0.05) from parents who were both
      obese, yet this was not significant after adjustment for age of parents. Also,
      there were no other significant differences in sex distribution of offspring
      according to body mass index, age, or social class of parents. The conditions of
      the original 1949 study of Angel ( 1949 ) (which proposed a sex-linked lethal
      recessive gene) were simulated by selecting couples with at least one obese
      daughter. In this subset, (n = 409), obesity in fathers and mothers was
      associated with 26% of offspring being male compared with 19% of offspring from a
      non-obese father and obese mother. Finally we conclude that families with an
      obese father have a higher proportion of male offspring. These results do not
      support the long-established hypotheses of a sex-linked recessive lethal gene in
      the etiology of obesity.

PMID- 21846212
TI  - Early detection of prostate cancer: is screening in general practice justifiable?

PMID- 21846209
TI  - Inflammation and genetics: an insight in the centenarian model.
AB  - The number of centenarians is growing worldwide. This specific cohort has aroused
      the attention of scientists worldwide and is considered one of the most valuable
      models to study the mechanisms involved in the aging process. In fact, they have
      reached the extreme limits of human life span and, most important of all, they
      show relatively good health being able to perform their routine daily life.
      Because they have escaped the common lethal diseases, the role of their genetic
      background has been brought into focus. In fact, sequence variations, in a
      variety of pro- or anti-inflammatory cytokine genes, have been found to influence
      successful ageing and longevity. The key role played by cytokines has been also
      confirmed in centenarians as we know that inflammation has been related to
      several pathological burdens (e.g., obesity, atherosclerosis, and diabetes).
      Successful ageing seems to be related to an optimal functioning of the immune
      system, pointing out that polymorphisms for the immune system genes, which are
      involved in the regulation of immune-inflammatory responses, may play a key role
      in the genetics of ageing. This review provides an update in the field of ageing
      related to inflammation and genetics.

PMID- 21846214
TI  - Learning characteristics of the CERAD word list in an elderly VA sample.
AB  - The Consortium to Establish a Registry for Alzheimer's Disease (Morris et al.,
      1989) neuropsychological battery, including its 10-word list-learning task,
      remains in clinical and research use. The present study examined learning
      characteristics of this word list in a clinical series of elderly military
      veterans referred for neuropsychological evaluation of suspected dementia.
      Findings are presented establishing specific normative data by age, education,
      race, and diagnosis on learning outcomes including total new learning, delayed
      recall, and recognition memory. In addition, variables such as primacy and
      recency, intrusion and repetition errors, learning slope, and across-trial
      consistency are reported. There were no unexpected between-group findings, and
      the current data may be valuable as a reference when patients with similar
      demographic and health backgrounds are evaluated.

PMID- 21846213
TI  - Conformational changes in the novel redox sensor protein HbpS studied by site
      directed spin labeling and its turnover in dependence on the catalase-peroxidase
      CpeB.
AB  - AIMS: To establish conditions to study the oligomeric assembly of heme-binding
      protein (HbpS) in solution by applying the tools of site-directed spin labeling
      combined with pulse electron paramagnetic resonance (SDSL EPR) spectroscopy, as
      well as to analyze redox stress-based conformational changes in HbpS subunits
      within the oligomer in solution. In vivo elucidation of molecular mechanisms that
      control the downregulation of the novel redox-system HbpS-SenS-SenR. RESULTS:
      Using a set of specifically generated HbpS mutants, and SDSL EPR spectroscopy, we
      show the octomeric assembly of HbpS in solution, and demonstrate that iron
      mediated stress induces conformational changes in HbpS subunits within the
      octamer. We further demonstrate that the catalase-peroxidase CpeB protects HbpS
      from hydrogen peroxide (H(2)O(2))-mediated oxidative attack in vivo. Moreover,
      chromosomal inactivation of cpeB results in an enhanced sensitivity of the mutant
      to redox-cycling compounds. INNOVATION: SDSL EPR has been used in this work for
      the first time to monitor redox-mediated conformational changes in a redox
      sensing protein in solution. This work substantially explains redox-dependent
      dynamics in HbpS at the atomic level, and presents novel molecular mechanisms
      supporting downregulation of a signaling cascade. CONCLUSION: Iron-mediated
      stress induces movements of subunits within the HbpS octomeric assembly. We
      suggest a motion of the C-terminal alpha-helix toward the preceding helical
      segment. These events upregulate the activity of the HbpS-SenS-SenR system, in
      which HbpS acts as an accessory element. The mycelia-associated CpeB, under the
      control of HbpS-SenS-SenR, protects the extracellular HbpS from oxidation in
      vivo. Thus, de novo synthesized HbpS proteins downregulate the HbpS-SenS-SenR
      signaling cascade.

PMID- 21846215
TI  - IQ and ability across the adult life span.
AB  - The experience of cognitive decline can be a potent source of anxiety and concern
      for many people. While an IQ consistent with estimated optimal levels or
      previously recorded scores may indicate no significant change in cognitive
      function, the patient may be accurately reporting a normal age-related
      deterioration in actual ability. The aim of this article is to chart the age
      related changes in intellectual abilities evident on the Wechsler Adult
      Intelligence Scales-Fourth Edition (WAIS-IV). The norms from the WAIS-IV manual
      were examined to plot the age-related changes in Full-Scale IQ (FSIQ) and
      composite scores across the adult life span, while holding actual ability level
      constant across the age groups. Here we present a graphical representation of the
      normal cognitive developments and declines in FSIQ, Verbal Comprehension,
      Perceptual Reasoning, Working Memory, and Processing Speed across the adult life
      span. This graphical representation provides a rational basis for the
      identification of atypical profiles/complaints of cognitive deterioration that
      may require further specialist neuropsychological evaluation. These graphs can be
      used to provide reassurance for healthy adults with concerns of cognitive decline
      and as an educative tool for their referring agencies.

PMID- 21846216
TI  - Differential sensitivity of TOMAL subtests and index scores to pediatric
      traumatic brain injury.
AB  - The objective of the present study was to examine and compare the subtest, index,
      and factor scores of the Test of Memory and Learning (TOMAL), using receiver
      operating characteristic curves, to investigate their sensitivity and specificity
      to traumatic brain injury (TBI) in children and adolescents. One hundred and
      fifty participants who had sustained TBI were compared to 150 controls matched on
      age and gender from the TOMAL's standardization sample. Results indicated that
      the greatest area under the curve (AUC) was for the Object Recall (OR) subtest
      score, the Composite Memory Index (CMI), and the attention factor score. The
      optimal CMI cutoff score for a TBI diagnosis was 83. When factor scores were
      compared, the attention factor and two verbal factors had significantly larger
      AUCs than the three nonverbal factors. These findings suggest that the OR subtest
      and CMI are most sensitive to TBI, and that when components were broken into
      factors with no overlapping subtests, attention and verbal memory were optimal
      for classifying TBI.

PMID- 21846217
TI  - Clock drawing and mini-mental state examination in patients with traumatic brain
      injury.
AB  - The aim of this study was to compare the performances of patients with mild,
      moderate, and severe traumatic brain injury (TBI) on the Clock Drawing Test
      (CDT), the Mini-Mental State Examination (MMSE), and neuropsychological measures
      as well as to correlate these measures with outcome assessed by the Extended
      Glasgow Outcome Score. This study was conducted in an acute care early
      rehabilitation setting on 102 patients with mild, 30 with moderate, and 30 with
      severe TBI. Patients with moderate and severe TBI showed more impairment on the
      CDT compared with those with mild TBI. Similar results were obtained for the
      MMSE, F ((2,159df)) = 3.789, p = .025. Finally, a receiver-operating
      characteristic analysis showed that the CDT and the Trail-Making Test-Part B (TMT
      B) in combination have the potential for prediction of outcome in a TBI
      population. In conclusion, this combination of the CDT and the TMT-B seems to be
      useful for early assessment of TBI patients.

PMID- 21846218
TI  - Patients with major depression show intact memory performance--given optimal
      conditions.
AB  - In the present study, verbal and visual memory functioning in a group of
      recurrent major depressive disorder patients were investigated. The study
      included 48 participants: 24 patients and 24 control subjects. Verbal and visual
      memory were investigated using the California Verbal Learning Test and the Rey
      Complex Figure Test. The results show that the depressed patients performed
      significantly worse compared with the controls on the very first trial in the
      verbal memory test. On all other conditions, the patients showed intact verbal
      memory, while visual memory was impaired. It is important to highlight the intact
      verbal memory performance in the acute phase of illness to detect cognitive
      strengths in this patient group.

PMID- 21846219
TI  - Psychometric data for the NFL neuropsychological test battery.
AB  - As part of a comprehensive league-wide study of concussion, the National Football
      League's Committee on Mild Traumatic Brain Injury sponsored a neuropsychological
      testing program from 1996 through 2001. Nearly 1,000 athletes participated
      voluntarily in the study. Traditional paper-and-pencil neuropsychological tests
      were used for baseline assessment. Neuropsychological tests used in the study
      included the Hopkins Verbal Learning Test-Revised, the Brief Visuospatial Memory
      Test-Revised, Trail-Making Tests (Parts A and B), and the Controlled Oral Word
      Association Test. We present a factor analysis of these baseline data on 513
      athletes who completed all of the neuropsychological tests and present normative
      psychometric data on the multiple baseline tests employed.

PMID- 21846221
TI  - Length of illness does not predict cognitive dysfunction in chronic fatigue
      syndrome.
AB  - Neuropsychological studies have shown cognitive impairment in chronic fatigue
      syndrome (CFS), particularly in information-processing speed. The aim of this
      study was to examine the evolution of cognitive impairment in CFS. The evolution
      is one of the most disabling aspects of the CFS, and it has received little
      attention in the literature. Fifty-six women with CFS were assessed with
      neuropsychological tests. Patients were divided into three groups based on the
      duration of the disease. There were no differences between groups in terms of
      cognitive function. The cognitive impairment in CFS was not found to be more
      severe with longer disease duration. These data suggest that there is no
      progressive cognitive impairment in patients with CFS. Therefore, the cognitive
      deficits in CFS should be treated with cognitive rehabilitation programs focused
      on improving emotional distress associated to the illness and on promoting
      functional abilities.

PMID- 21846220
TI  - Predictors of HVOT performance in Parkinson's disease.
AB  - Evidence suggests that the Hooper Visual Organization Test (HVOT) has naming and
      executive components that vary in size depending on neurological diagnosis. The
      current study used a sample of individuals with Parkinson's disease (PD) to
      demonstrate for the first time that an executive measure can be the best
      predictor of HVOT performance. Forty-eight nondemented and nondepressed
      individuals with idiopathic PD completed the HVOT and other measures of
      visuoperception, executive function, and visual confrontation naming. Despite
      average performance on all neuropsychological measures, an executive measure,
      time to complete Trail-Making Test Part B minus time to complete Part A, was
      clearly the best predictor of HVOT performance in a standard regression. The
      pattern of neurocognitive predictors is unlike that reported in healthy
      individuals and other patient samples. This finding suggests that the presence of
      a neuropathological process can alter neurocognitive correlates even when
      performance is intact, and supports the contention that executive function is
      paramount in the cognitive profile associated with PD.

PMID- 21846225
TI  - Introduction: long-term care needs in Hong Kong.

PMID- 21846226
TI  - Long-term care policy in Hong Kong: challenges and future directions.
AB  - In comparison to residential care services, home and community care services in
      Hong Kong remain underfunded and underdeveloped. The government's long-term care
      policies have resulted in an overreliance on subsidized long-term care services
      in the form of institutional care services. The quality of services offered by
      private residential care facilities is a cause for concern. Population aging,
      evolving family structures, and changes in residential living patterns are
      expected to continue to put a strain on resources for services for the elderly in
      the near future. This article provides an overview of the many issues surrounding
      long-term care in Hong Kong and offers potential directions for the future
      development of long-term care services.

PMID- 21846227
TI  - Psychological distress among Chinese adult-child caregivers: the effects of
      behavioral and cognitive components of care.
AB  - This study examined the effects of behavioral and cognitive components of care on
      caregivers' psychological distress among adult children who were the primary
      caregivers of frail older adults living in the community in Hong Kong. The sample
      was drawn from a 2008 data set that was used to determine the eligibility for
      long-term care in Hong Kong. Logistic regressions evaluated the association
      between caregiver psychological distress and the behavioral and cognitive
      components of care with a range of covariates. About 35% of the caregivers showed
      signs of psychological distress. Caregivers who provided more care for
      instrumental activities of daily living (IADLs), demonstrated a greater intensity
      of care, lived with the care recipient, or became dissatisfied with the amount of
      support received from other family members and friends were more likely to
      express psychological distress. Providing emotional support to the care recipient
      and being unable to continue providing care were negatively associated with
      psychological distress, after controlling for the sociodemographic status and
      health status of the care recipient.

PMID- 21846230
TI  - The Clark Tibbits Award Lecture.

PMID- 21846228
TI  - An evaluation of the factor structure of the Instrumental Activities of Daily
      Living Involvement and Capacity scales of the Minimum Data Set for Home Care for
      elderly Chinese Community dwellers in Hong Kong.
AB  - The objective of this study was to evaluate the factor structure of the
      Instrumental Activities of Daily Living (IADL) Involvement and Capacity scales of
      the Chinese version of the Minimum Data Set-Home Care (MDS-HC) in a sample of
      Chinese older adults living in Hong Kong (n=3,523). The results of confirmatory
      factor analyses supported the one-factor model for both IADL Involvement and IADL
      Capacity scales. Evidence indicated that both scales had good internal
      consistency (.88) and were reliable and valid in assessing IADL among elderly
      Chinese community dwellers.

PMID- 21846231
TI  - Marginal gerontology and the curriculum palette.
AB  - The thrust of human development over the life course is individuation. Birth
      groups grow more heterogeneous with age. Aside from there being a number of
      commonalities among members of cohorts, the stamp of life lived tends to increase
      individual differences, whether these be in organ functioning or other physical
      measures or social, psychological or economic characteristics. At the same time,
      there are large modal tendencies with age that have import for policy making,
      service planning, and social institutions. This article asks: How does
      gerontology reconcile the individual and the group? What must educational
      gerontology do to help capture individuation? How can the educational gerontology
      curriculum encourage not just the accumulation of facts and information but a
      deeper wisdom, a knowing, about what it means to grow older? This article
      suggests that our content, our methods, and our values have limitations. The
      standard educational gerontology curriculum provides the primary colors or core
      for understanding but needs to be augmented with a fuller palette. This palette
      should be both more comprehensive and less prescriptive, being adaptable to
      minority, sub-group, and other cultural contexts. The aim is to complement
      gerontology's traditional focus on the what and the how, with an appreciation of
      the who and the why, recognizing both the external persona and the internal self
      as important to understanding and teaching about human aging.

PMID- 21846232
TI  - Teaching and learning experiences in a collaborative distance-education
      environment.
AB  - The Great Plains Distance Education Alliance (Great Plains IDEA) emphasizes the
      importance of a collaborative environment for instructors and students in
      distance education. The authors highlight a number of important principles for
      distance-education programs and point out similarities and differences when
      compared to traditional face-face-to classes such as communication, classroom
      management, connectivity, and technical challenges. They summarize general topics
      concerning the faculty, the syllabus, office hours, the calendar, and
      announcements. Three essential lesson components are noted: an overview, the
      lesson itself, and supplemanetary material. The authors also take the student
      perspective, emphasizing the diversity of students, the importance of computer
      proficiency, and student interactions. Finally, they summarize a first round of
      course evaluations in the Great Plains IDEA gerontology master's program.

PMID- 21846233
TI  - European Master's Program in Gerontology (EuMaG): goals, curriculum, and
      students.
AB  - The European Master's Program in Gerontology (EuMaG) started in September 2003
      with support from the European Commission. The EuMaG is a modular, 2-year, part
      time international training program about the aging process and its societal
      implications. The multidisciplinary curriculum comprises four domains of
      gerontology (i.e., social gerontology, psychogerontology, health gerontology, and
      biogerontology). Recently, a module on research and academic writing has been
      added to the core program. EuMaG emphasizes international comparison, focusing on
      current European debates concerning-among other things-policy and care for older
      adults. Members of several gerontology programs deliver the program across
      Europe. Guest lecturers from the wider EuMaG consortium are invited during the
      core modules. All institutes are involved in aging research, which provides ample
      opportunities to inform students about the latest research. Part of the standard
      curriculum is the Summer School, which is a collaborative endeavor of the VU
      University Amsterdam and one of the partner universities of the larger European
      network. Since the start of EuMaG in 2003, a mix of participants with respect to
      age, nationality, and background has entered EuMaG. More than 100 students
      subscribed for (parts) of the EuMaG program. Students evaluate the EuMaG as
      highly informative and inspiring and appreciate the possibility to build an
      international network of gerontologists.

PMID- 21846234
TI  - The Great Plains IDEA Gerontology Program: an online, interinstitutional graduate
      degree.
AB  - The Great-Plains IDEA Gerontology Program is a graduate program developed and
      implemented by the Great Plains Interactive Distance Education Alliance (Great
      Plains IDEA). The Great Plains IDEA (Alliance) originated as a consortium of
      Colleges of Human Sciences ranging across the central United States. This
      Alliance's accomplishments have included faculty development in online distance
      education, development of cooperative approaches to graduate education among
      faculty and institutions, and development of quality graduate programming. In
      this article, the process of developing a national model for collaboration is
      discussed, the barriers that the program overcame are highlighted, and the
      lessons learned through implementing a graduate program in gerontology are
      presented. The outcomes of the assessment conducted across seven states to
      determine interest in an online gerontology graduate program and the findings
      from program evaluation efforts are presented.

PMID- 21846235
TI  - Demonstrating the value of gerontology in troubled times: taking the Future Self
      exercise from the classroom to the community.
AB  - Gerontologists at state-funded universities are being challenged to demonstrate
      the value of their programs amid looming budget cuts. This article, third in a
      series reporting research and development of the Future Self exercise, suggests
      that the latest iteration of the exercise is an effective way to demonstrate the
      value of a gerontology program to community members. The article describes
      adaptation of the classroom exercise, and results of evaluation of presentations
      of the adapted exercise to 15 community and professional groups in Nebraska and
      Kansas during the past two years. Implications for future research and practice
      are identified.

PMID- 21846236
TI  - A landscape for training in dementia knowledge translation (DKT).
AB  - Meaningful translation of dementia research findings from the bench to the
      bedside is dependent on the quality of the knowledge to transfer and the
      availability and skills of investigators engaged in the knowledge translation
      process. Although there is no shortage of research on dementia, the latter has
      been more challenging. Results from a survey of 173 researchers from across
      Canada suggest that workshops and self-paced online training in dementia
      knowledge translation are needed to bridge the research-to-practice gap. Sharing
      information among professionals and with the public and formulating actionable
      messages to policy makers are primary goals.

PMID- 21846237
TI  - Students and teachers' preferences for undergraduate dementia education in
      Western Australia.
AB  - Medical graduates require positive attitudes toward older people with cognitive
      impairment, in addition to knowledge and skills in the diagnosis and management
      of dementia. The Student Training Project in Dementia (STriDE) project was
      conducted to ensure that these needs are met through curricula in Western
      Australian medical schools. Two medical schools in Perth, Western Australia,
      participated. Mixed methods were utilized comprising a) focus groups and
      interviews and b) a survey of teachers and students. Participants recommended
      clearer structure and standardization in the curriculum to ensure that all
      students receive similar educational experiences regardless of hospital
      placement. Both teachers, and to a lesser extent students, held positive
      attitudes toward older people. Teachers tended to be more dissatisfied with
      current curricula than students. Teachers and learners endorsed a broad range of
      teaching and learning methods, assessments, and skills/competencies. The results
      of this study present major challenges for professional entry dementia education
      given the breadth, flexibility, and depth of dementia education recommended by
      teachers and learners.

PMID- 21846238
TI  - Paradise lost?: rural life and nutritional well being in the 21st century.

PMID- 21846239
TI  - Food intake patterns and body mass index in older adults: a review of the
      epidemiological evidence.
AB  - The relationship between food intake patterns and obesity remains unclear. The
      objective of the present review was to evaluate the current body of literature on
      food intake patterns of older adults and their associations with weight status,
      including obesity and waist circumference. Eleven observational studies were
      identified and reviewed. Diets characterized by more favorable dietary scores or
      indices were generally inversely related to body mass index. Results from data
      driven approaches were inconsistent. Findings from this literature review suggest
      that there is no clear relationship between food intake patterns and body mass
      index or waist circumference in older adults. Limitations, including
      heterogeneity of food intake patterns and study populations, hinder the ability
      to make clear comparisons. Continued efforts to elucidate the relationship
      between food intake patterns and weight status indicators in older adults,
      including longitudinal analyses and use of novel statistical approaches for food
      intake pattern identification, are warranted.

PMID- 21846240
TI  - Using photovoice methodology to investigate facilitators and barriers to food
      acquisition and preparation by rural older women.
AB  - This research investigates facilitators and barriers that rural women aged 65 to
      75 years in Southwestern Ontario experience in acquiring and preparing food
      through the use of photovoice methodology. Eighteen participants in five rural
      communities used a camera and log book to document their experiences and
      perspectives relating to the acquisition and preparation of food, and they each
      participated in two focus groups to engage in critical dialogue and knowledge
      sharing regarding the meaning and significance of the pictures they took.
      Analysis of photographs, log books, and focus group data revealed 13 themes, 3
      emerging as facilitators to food acquisition and preparation (availability of
      food, social networks and values, personal values and resources), 5 as barriers
      (adjusting to changing family size, winter weather, food labeling issues, grocery
      shopper resources, limited physical capacity), and 5 as both facilitators and
      barriers (economics, valuing a healthy diet, technology changes, transportation,
      location and nature of grocery stores). Data also revealed rurality, age, and
      gender as foundationally influential factors affecting rural older women's food
      acquisition and preparation.

PMID- 21846241
TI  - Purchasing habits of senior farmers' market shoppers: utilizing the theory of
      planned behavior.
AB  - The purpose of this study was to understand fresh fruit and vegetable purchasing
      habits among senior farmers' market shoppers using the theory of planned
      behavior. A survey instrument was developed to collect information on seniors'
      fruit and vegetable purchasing habits. A convenience sample of seniors shopping
      at farmers' markets was employed. A total of 184 surveys were collected.
      Respondents were divided into two groups based on response to a question of
      whether they received Senior Farmers' Market Nutritional Program (SFMNP) checks:
      35 were on the SFMNP and 149 were not. Results indicated attitudes, subjective
      norms (SN), and perceived behavioral control (PBC) were all significantly
      correlated with intentions at the p < 0.01 level. Attitude had the strongest
      association with intentions (0.730), followed by PBC (0.666) and SN (0.587).
      Regression analysis was significant and explained 66% of the variance (F =
      86.151, p < 0.001, adjusted R square = 0.656). Results indicated attitude to be
      the strongest predictor of seniors' intentions to purchase more fresh fruits and
      vegetables at farmers' markets. Senior programs may find this information useful
      when promoting fresh fruits and vegetables for senior citizens. These findings
      may also benefit farmers' markets while promoting fresh fruits and vegetables.

PMID- 21846242
TI  - Healthy eating perceptions of older adults living in Canadian rural and northern
      communities.
AB  - Aging produces physiologic changes that can affect the nutritional health of the
      older adult. It is estimated that 80% of community-dwelling older adults have
      inadequate intakes of four or more nutrients. Socioeconomic factors, such as
      income and geographic location, can also play an important role in nutritional
      status; however, limited research is available that specifically explores this.
      The purpose of this qualitative study was to examine the healthy eating
      perceptions of older adults residing in rural and northern communities in one
      Canadian province. Five focus groups were conducted in three rural and two
      northern Manitoba communities. Thirty-nine older adults participated in audio
      recorded focus groups. Five themes emerged from the discussions. All respondents
      stated that healthy eating was important, but knowledge deficits were observed
      regarding label reading, understanding and visualizing portion sizes, and vitamin
      D recommendations and sources. Food programs were not commonly attended by
      participants due to availably and resistance. Regularly delivered nutrition
      education programs would assist in providing current nutrition information to
      older adults and their families in rural settings.

PMID- 21846243
TI  - Rural and urban older African caregivers coping with HIV/AIDS are nutritionally
      compromised.
AB  - This article describes the nutritional status of a group of rural and urban free
      living African older surrogate parents caring for HIV/AIDS orphans and
      grandchildren. Multiple sources of data collection were used, including
      anthropometry, biochemical analyses, and quantitative questionnaires. The diets
      of these older participants were marginal. The rural to urban geographical
      transition in these older persons is characterized by a better micronutrient and
      trace element intake; however, urban dwellers also had higher fat intakes,
      increasing the risk for cardiovascular disease. These results suggest that to be
      a surrogate grandparent provides a special meaning to the life of men that needs
      to be better understood. However, the diets of these older people caring for
      HIV/AIDS-affected children were more compromised than those of non-caregivers.

PMID- 21846244
TI  - Oral health status and chewing ability is related to mini-nutritional assessment
      results in an older adult population in Thailand.
AB  - In a cross-sectional study, we investigated the relationship of Mini-Nutrition
      Assessment (MNA) results with chewing ability tests and oral examinations (number
      of teeth present and functional tooth units (FTUs)). The participants were 612
      older people (Mean [SD] age: 68.8 [5.9]). According to the MNA score, 25.1% of
      participants were categorized as having normal nutrition, 67.2% were categorized
      as at risk of malnourishment, and 7.7% were categorized as having malnutrition.
      The mean numbers of teeth present and FTUs were [15.5] and [8.9], respectively.
      The ANCOVA analyses adjusted for age and gender showed that participants with
      malnutrition had lower numbers of teeth present (8.8), FTUs (8.4), and chewing
      ability (6.8) than those with normal nutrition (13.3, 10.4 and 7.8) (p < 0.05).
      Nutritional status was associated with mean numbers of teeth present, FTUs, and
      chewing ability. Therefore, it was concluded that retention of natural teeth with
      appropriate numbers of FTUs by replacing missing teeth with dentures and
      improving chewing ability will help the reduce risk of malnutrition in older
      adults.

PMID- 21846245
TI  - Anthropometric, body composition, and blood pressure measures among rural elderly
      adults of Asian Indian origin: the Santiniketan aging study.
AB  - The number of older adults is increasing in industrialized and in developing
      countries. The present community-based cross sectional work was undertaken to
      study the anthropometric, body composition, and blood pressure characteristics of
      rural-dwelling elderly adults of Asian Indian origin. A total of 300 individuals
      (Male = 157 and Female = 143) from the Bolpur-Sriniketan area of West Bengal,
      India, took part in the study. Participants were divided into four age-groups:
      Group I, 55-59 years (Male:Female = 55:61); Group II, 60-64 years (Male:Female =
      41:33); Group III, 65-69 years (Male:Female = 27:21); Group IV, 70 years and
      older (Male:Female = 34:28). Anthropometric measures were taken using standard
      techniques. Body mass index, waist-hip ratio, and the sum of four skin folds were
      subsequently computed. Body composition measures, namely percentage of body fat,
      fat mass, fat free mass, arm muscle circumference, arm muscle area, and arm fat
      area, were calculated accordingly. Left-arm systolic (SBP) and diastolic blood
      pressures (DBP) were also measured, and mean arterial pressure was subsequently
      calculated. Overall observations in the study population indicate a predominance
      of body weights below the normal body mass index of 25 kg/m(2). More than half
      the subjects reported the lack of adequate sanitation facilities and education
      levels were generally low. Rates of smoking (65.6%) and habitual consumption of
      alcohol (38.9%) were high in male participants. Upon comparison across the four
      age groups, results revealed decreases in percent body fat, fat mass, and mid
      upper arm muscle circumference for Groups III and IV versus Group I for men and
      for Group IV versus I for women. The overall trend for both SBP and DBP was for
      small increases with age in men in contrast to slight decreases with age in
      women. Our findings of generally low body weights, detrimental age-related
      changes in body composition, and a number of other health-related concerns
      highlight the high level of nutritional risk in rural dwelling older adults of
      Asian Indian Origin. Clinicians conducting assessments in this population need to
      take these measures into account in order to fully account for potential health
      risks.

PMID- 21846247
TI  - Early, high quality enteral nutrition significantly improves outcome in head
      trauma patients.

PMID- 21846246
TI  - Targeting expression of the leukemogenic PML-RARalpha fusion protein by
      lentiviral vector-mediated small interfering RNA results in leukemic cell
      differentiation and apoptosis.
AB  - Acute promyelocytic leukemia (APL) results from a chromosomal translocation that
      gives rise to the leukemogenic fusion protein PML-RARalpha (promyelocytic
      leukemia-retinoic acid alpha receptor). Differentiation of leukemic cells and
      complete remission of APL are achieved by treatment of patients with
      pharmacological doses of all-trans retinoic acid (ATRA), making APL a model
      disease for differentiation therapy. However, because patients are resistant to
      further treatment with ATRA on relapse, it is necessary to develop alternative
      treatment strategies to specifically target APL. We therefore sought to develop a
      treatment strategy based on lentiviral vector-mediated delivery of small
      interfering RNA (siRNA) that specifically targets the breakpoint region of PML
      RARalpha. Unlike treatment with ATRA, which resulted in differentiation of
      leukemic NB4 cells, delivery of siRNA targeting PML-RARalpha into NB4 cells
      resulted in both differentiation and apoptosis, consistent with the specific
      knockdown of PML-RARalpha. Intraperitoneal injection of NB4 cells transduced with
      lentiviral vectors delivering PML-RARalpha-specific siRNA but not control siRNA
      prevented development of disease in nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) mice. Taken together, these results indicate that
      development of PML-RARalpha-specific siRNA may represent a promising treatment
      strategy for ATRA-resistant APL.

PMID- 21846248
TI  - Efficacy and safety of dopamine agonists in traumatic brain injury: a systematic
      review of randomized controlled trials.
AB  - In the intensive care unit, dopamine agonists (DA) have been used in traumatic
      brain injury (TBI) patients to augment or accelerate cognitive recovery and
      rehabilitation. However, the efficacy and safety of DA in this population is not
      well established. We conducted a systematic review of randomized controlled
      trials (RCTs) examining the clinical efficacy and safety of DA in patients with
      TBI. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled
      Trials, comparing DA to either placebo, standard treatment, or another active
      comparator. There was no restriction for age, date, or language of publication.
      Sensitivity analyses were planned to evaluate the potential effect of timing of
      TBI, age, drugs, and year of publication on efficacy. Among the 790 citations
      identified, 20 RCTs evaluating methylphenidate, amantadine, and bromocriptine
      were eligible. Significant clinical heterogeneity was observed between and within
      studies, which precluded any pooling of data. Efficacy outcomes included mainly
      neuropsychological measures of cognitive functioning. A total of 76 different
      neuropsychological tests were used, but most of them (59%) only once. Only 5
      studies systematically assessed safety. No trend could be drawn from the analysis
      of efficacy and safety. Important sources of bias in the studies were of major
      concern. Considering the absence of consensus regarding clinical outcome, the
      lack of safety assessment, and the high risk of bias in the included trials, more
      research is warranted before DA can be recommended in critically ill TBI
      patients.

PMID- 21846249
TI  - Preface to second edition of special issue: social work with the military:
      current practice challenges and approaches to care.

PMID- 21846250
TI  - No one leaves unchanged: insights for civilian mental health care professionals
      into the military experience and culture.
AB  - This article aims to elucidate an understanding of military culture and
      experience, so as to better frame the services offered by civilian clinicians.
      Service members indoctrinated into such an influential culture can experience
      adjustment problems upon reentry into the larger society, and thus professional
      counselors and social workers must be ready to address the reintegration process
      with veteran clients. Furthermore, this article highlights a few of the major
      mental health concerns that are prevalent in combat veterans, especially for
      those returning from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom
      (OEF), and presents a brief overview of treatment modalities implemented both
      within and outside of the military. Practical therapeutic suggestions for
      clinicians with little or no knowledge of the military are discussed. The
      objective is to educate and prepare civilian mental health practitioners to
      administer culturally sensitive prevention and intervention services to meet the
      unique needs of this population.

PMID- 21846251
TI  - Care coordination in military traumatic brain injury.
AB  - Traumatic brain injury (TBI)-an injury to the brain that may or may not create
      lasting impairment for the survivor-has been recognized as a major public health
      problem by the Centers for Disease Control ( Langlois, Rutland-Brown, & Thomas,
      2006 ). Ongoing conflicts in Iraq and Afghanistan have highlighted the problem
      for the military ( Warden, 2006 ). Many soldiers are exposed to severe impact to
      the head resulting in TBI. As those with TBI transition to their home locality,
      civilian social workers and other providers will be involved in their care. This
      article examines the medical and emotional implications of mild TBI and offers
      suggestions for care of those affected, both the service member and his/her
      family.

PMID- 21846252
TI  - Women and men who have served in Afghanistan/Iraq: coming home.
AB  - The experience of war changes people - some will acknowledge that the changes are
      positive and some will feel the opposite or a combination, but that it changes a
      person cannot be disputed. For those who return, the experience of reintegration
      to civilian life or as a respite before redeployment can present numerous
      challenges. The research presented in this article reports the findings on
      interviews with over 800 service members who had returned from either Afghanistan
      or Iraq. The Post Deployment Reintegration Scale was used to refine the areas
      that respondents identified as positive or negative in their reintegration
      experience. Implications for practice with returning service members are noted.

PMID- 21846253
TI  - Family resilience and the fortunes of war.
AB  - Military families have been a subject of concern due to increasing divorce rates
      and child maltreatment that have been directly linked to the number and length of
      combat deployments. In contrast many military families show positive resilience
      in the wake of multiple deployments. This article looks at several special
      situations where military families are faced with serious challenges after
      deployment: soldiers returning with post-traumatic stress disorder, soldiers
      receiving serious injuries, and those killed in action. McCubbin's Family
      Resilience Model is applied as a theoretical tool for understanding not only the
      stressors military families face, but other factors that buffer stress and assist
      in problem solving and coping.

PMID- 21846254
TI  - Operation Iraqi Freedom/Operation Enduring Freedom: exploring wartime death and
      bereavement.
AB  - Military deaths are often sudden, unanticipated, traumatic, and/or violent in
      nature and involve the death of a young adult. More than 5,500 service members
      have died as a result of their service in the wars in Afghanistan (2001) and Iraq
      (2003) in combat- or non-combat- related incidences. As the death toll continues
      to rise, service members and their families struggle with the visible and
      invisible wounds of war. This article explores wartime death, trauma, and
      bereavement experienced by those survivors affected by service members who have
      died as a result of their military service in Operation Iraqi Freedom (OIF) and
      Operation Enduring Freedom (OEF). It recognizes the circumstantial and cultural
      factors of the death as well as the grief and trauma experiences of survivors.
      Resources and suggested interventions of support are highlighted.

PMID- 21846255
TI  - VA integrated post-combat care: a systemic approach to caring for returning
      combat veterans.
AB  - The Department of Veterans Affairs (VA's) mission is to care for those who have
      borne the battle. As medical technology has advanced, more and more of our
      returning combat Veterans survive what would have been fatal wounds in previous
      conflicts ( Gawande, 2004 ). But survival is only the immediate goal-our job is
      to restore Veterans to the greatest level of health, independence, and quality of
      life that is medically possible. The VA is achieving this goal through close
      collaboration with the Department of Defense (DoD) to facilitate a smooth
      transition and continuum of care that ensures Veterans and Service Members
      receive the care they deserve. This article describes VA's system of Veteran
      centered, post-combat care programs that rely on significant involvement of
      social workers to support Service Members, Veterans and their families through
      recovery, rehabilitation, and re-integration into their home communities.

PMID- 21846256
TI  - Psychological status as a function of residual scarring and facial asymmetry
      after surgical repair of cleft lip and palate.
AB  - Objective : Objective measure of scarring and three-dimensional (3D) facial
      asymmetry after surgical correction of unilateral cleft lip (UCL) and unilateral
      cleft lip (UCLP). It was hypothesized that the degree of scarring or asymmetry
      would be correlated with poorer psychological function. Design : In a cross
      sectional design, children underwent 3D imaging of the face and completed
      standardized assessments of self-esteem, depression, and state and trait anxiety.
      Parents rated children's adjustment with a standard scale. Setting : Glasgow
      Dental School, School of Medicine, College of Medical, Veterinary and Life
      Sciences. Patients : Fifty-one children aged 10 years with UCLP and 43 with UCL
      were recruited from the cohort treated with the surgical protocol of the CLEFTSIS
      managed clinical network in Scotland. Methods : Objective assessment to determine
      the luminance and redness of the scar and facial asymmetry. Depression, anxiety,
      and a self-esteem assessment battery were used for the psychological analysis.
      Results : Cleft cases showed superior psychological adjustment when compared with
      normative data. Prevalence of depression matched the population norm. The
      visibility of the scar (luminance ratio) was significantly correlated with lower
      self-esteem and higher trait anxiety in UCLP children (P  =  .004). Similar but
      nonsignificant trends were seen in the UCL group. Parental ratings of poorer
      adjustment also correlated with greater luminance of the scar. Conclusions : The
      objectively defined degree of postoperative cleft scarring was associated with
      subclinical symptoms of anxiety, depression, and low self-esteem.

PMID- 21846257
TI  - Nasal changes after presurgical nasoalveolar molding (PNAM) in the unilateral
      cleft lip nose.
AB  - PURPOSE: Nasal reconstruction for patients with unilateral cleft lip and palate
      (UCLP) is a challenge for the reconstructive surgeon. Presurgical nasoalveolar
      molding (PNAM) was introduced to reshape the cleft nasal structures prior to lip
      repair. This study analyzed two-dimensional nasal changes before and after PNAM
      in patients with complete UCLP. METHODS: Thirty UCLP patients (19 males; 11
      females) who received PNAM before lip repair were included in this study. PNAM
      was applied for 100 days. Nasal casts were obtained before and after PNAM.
      Frontal and 45 degrees  standardized digital photographs were taken from all
      casts, and a photogrammetric analysis (16 linear, six angular, and two area
      measurements) was performed. Paired Student's t tests were used to search for
      differences by time, and time versus side (cleft versus noncleft). RESULTS:
      Significant reduction of cleft columella deviation with an increase in columella
      length, nostril height, and axial inclination on the cleft side were recorded.
      This resulted in an increase in the projection of the nasal tip. The noncleft
      measurements remained without significant changes. The cleft nostril area
      increased significantly more than the noncleft side by 90% with PNAM treatment.
      Significant normal growth changes were observed in nasal width and nasal height.
      CONCLUSION: A favorable reshaping of the nose after PNAM was achieved, resulting
      in an improvement in form before lip surgery. These changes lead to improved
      nasal symmetry before primary lip and nasal reconstruction in UCLP patients.

PMID- 21846258
TI  - Palate dimensions in six-year-old children with unilateral cleft lip and palate:
      a six-center study on dental casts.
AB  - OBJECTIVE: To compare palatal dimensions in 6-year-old children with unilateral
      cleft lip and palate (UCLP) treated by different protocols with those of noncleft
      children. DESIGN: Retrospective intercenter outcome study. Patients : Upper
      dental casts from 129 children with repaired UCLP and 30 controls were analyzed
      by the trigonometric method. SETTING: Six European cleft centers. Main outcome
      measures : Sagittal, transverse, and vertical dimensions of the palate were
      observed. STATISTICS: Palate variables were analyzed with descriptive methods and
      nonparametric tests. Regarding several various characteristics measured on a
      relatively small number of subjects, hierarchical, k-means clustering, and
      principal component analyses were used. RESULTS: Mean values of the observed
      dimensions for five cleft groups differed significantly from the control (p <
      .05). The group with one-stage closure of the cleft differed significantly from
      all other cleft groups in most variables (p < .05). Principal component analysis
      of all 159 cases identified three clusters with specific morphologic
      characteristics of the palate. A similar number of treated children were
      classified into each cluster, while all children without clefts were classified
      in the same cluster. The percentage of treated children from a particular group
      that fit this cluster ranged from 0% to 70% and increased with age at palatal
      closure and number of primary surgical procedures. CONCLUSION: At 6 years of age,
      children with stepwise repair and hard palate closure after the age of two more
      frequently result in palatal dimensions of noncleft control than children with
      earlier palatal closure and one-stage cleft repair.

PMID- 21846259
TI  - Alleviation of post-radical prostatectomy cavernosal fibrosis: future directions
      and potential utility for PDE5 inhibitors.
AB  - Reversion of cavernosal fibrosis remains a controversial issue. The relative
      smooth muscle cells' loss that happens with cavernosal nerve damage and their
      impact on deterioration of erectile function were demonstrated in several
      studies. Furthermore, chronic ischemia that occurs with aging and medical co
      morbidities is associated with the reduction of nitric oxide-cyclic guanosine
      monophosphate and ultimately cavernosal fibrosis. Despite the encouraging recent
      results of the role of phosphodiesterase type 5 inhibitors in the prevention of
      post-prostatectomy erectile dysfunction, debate regarding the exact mechanism of
      PDE5 inhibitors in prevention, amelioration and reversion of penile fibrosis
      still exists. Recently, several reports suggested that PDE5 inhibitors may
      improve endothelial function and decrease arterial stiffness, introducing this
      class of compounds as potential drugs for the treatment of erectile dysfunction
      associated penile fibrosis. In this editorial, we intended to address the role of
      PDE5 inhibitors as a promising treatment to alleviate or reverse ED associated
      cavernosal fibrosis.

PMID- 21846260
TI  - Factor Xa subsite mapping by proteome-derived peptide libraries improved using
      WebPICS, a resource for proteomic identification of cleavage sites.
AB  - Proteomic identification of protease cleavage site specificity (PICS) is a recent
      proteomic approach for the easy mapping of protease subsite preferences that
      determines both the prime- and non-prime side specificity concurrently. Here we
      greatly facilitate user access by providing an automated and simple web-based
      data-analysis resource termed WebPics (http://clipserve.clip.ubc.ca/pics/). We
      demonstrate the utility of WebPics analysis of PICS data by determining the
      substrate specificity of factor Xa from P6-P6', an important blood coagulation
      protease that proteolytically generates thrombin from prothrombin. PICS confirms
      existing data on non-prime site specificity and refines our knowledge of factor
      Xa prime-site selectivity.

PMID- 21846261
TI  - Use of Trial 1 of the Test of Memory Malingering (TOMM) as a screening measure of
      effort: suggested discontinuation rules.
AB  - Trial 1 of the Test of Memory Malingering (TOMM) has been suggested as a
      screening tool, with several possible cut-off scores proposed. The purpose of the
      present study was to replicate the utility of previously suggested cut-off scores
      and to characterize neuropsychological profiles of persons who "pass" the TOMM
      but obtain Trial 1 scores < 45 and of persons with cognitive disorders. A total
      of 229 veterans were administered the TOMM as part of a neuropsychological
      evaluation. Trial 1 scores >= 41 and <= 25 showed good utility as discontinuation
      scores for adequate and poor effort, respectively, beyond which administration of
      additional trials were unnecessary. Findings suggest better Trial 1 performance
      is significantly related to better speeded mental flexibility and memory.

PMID- 21846262
TI  - Questioning implicit motor learning as instantiated by the pursuit-tracking task.
AB  - The effect of concurrent visual feedback on the implicit learning of repeated
      segments in a task of pursuit tracking has been tested. Although this feedback
      makes it possible to regulate the positional error during the movement, it could
      also induce negative guidance effects. To test this hypothesis, a first set of
      participants (N=42) were assigned to two groups, which performed either the
      standard pursuit-tracking task based on the experimental paradigm of Pew ( 1974 ;
      group F-ST), or a task called "movement reproduction" in which the feedback was
      suppressed (group noF-ST). A second set of participants (N=26) performed in the
      same feedback condition groups but in a dual-task situation (F-DT and noF-DT;
      Experiment 2). The results appear to confirm our predictions since the
      participants in groups without feedback, contrary to those in groups with
      feedback, succeeded with practice in differentiating their performances as a
      function of the nature of the segments (repeated or nonrepeated) both in simple
      (Experiment 1) and in dual-task (Experiment 2) situations. These experiments
      indicate that the feedback in the pursuit-tracking task induces a guidance
      function potentially resulting in an easiness tracking that prevents the
      participants from learning the repetition.

PMID- 21846263
TI  - Cytotoxic compounds from the leaves of Gaillardia aristata Pursh. growing in
      Egypt.
AB  - Ten compounds, neopulchellin (1), 6alpha- hydroxyneopulchellin (2), beta
      sitosterol-3-O-beta-D-glucoside (3), apigenin (4), quercitin (5), eupafolin (6),
      kaempferol-3-methoxy-7-O-alpha-L-rhamnoside (7), apigenin-7-O-beta-D
      glucopyranoside (8), alpha-amyrin (9) and beta-sitosterol (10), were isolated
      from the leaves of Gaillardia aristata by applying bioassay guided fractionation.
      The cytotoxicity was traced against two human cancer cell lines (breast (MCF7)
      and colon (HCT116)). The highest cytotoxicity was revealed by compounds 1 and 2
      (isolated from chloroform extract); with IC(50) values of 0.43, 0.32 ug mL(-1)
      against MCF7 and 0.46, 0.34 ug mL(-1) against HCT116, respectively. Compounds 9
      and 10 (isolated from the n-hexane extract) exhibited lower IC(50) values of
      3.05, 2.35 ug mL(-1) against MCF7 and 3.05, 2.35 ug mL(-1) against HCT116,
      respectively, while compounds 4-7 obtained from the ethyl acetate extract
      revealed the lowest cytotoxicity. Identification of the aforementioned compounds
      was carried out on the basis of their physico-chemical properties and spectral
      analysis (UV, EI/MS, 1D and 2D).

PMID- 21846264
TI  - ChemT, an open-source software for building template-based chemical libraries.
AB  - In computational chemistry, vast quantities of compounds are generated, and there
      is a need for cheminformatic tools to efficiently build chemical compound
      libraries. Several software tools for drawing and editing compound structures are
      available, but they lack options for automatic generation of chemical libraries.
      We have implemented ChemT, an easy-to-use open-source software tool that
      automates the process of preparing custom-made template-based chemical libraries.
      ChemT automatically generates three-dimensional chemical libraries by inputting a
      chemical template and the functional groups of interest. The graphical user
      interface of ChemT is self-explanatory, and a complete tutorial is provided.
      Several file formats are accepted by ChemT, and it is possible to filter the
      generated compounds according to different physicochemical properties. The
      compounds can be subject to force field minimization, and the resulting three
      dimensional structures recorded on commonly used file formats. ChemT may be a
      valuable tool for investigators interested in using in silico virtual screening
      tools, such as quantitative structure-activity relationship modelling or
      molecular docking, in order to prioritize compounds for further chemical
      synthesis. To demonstrate the usefulness of ChemT, we describe an example based
      on a thieno[3,2-b]pyridine template. ChemT is available free of charge from our
      website at http://www.esa.ipb.pt/~ruiabreu/chemt .

PMID- 21846265
TI  - Measuring the approximate number system.
AB  - Recent theories in numerical cognition propose the existence of an approximate
      number system (ANS) that supports the representation and processing of quantity
      information without symbols. It has been claimed that this system is present in
      infants, children, and adults, that it supports learning of symbolic mathematics,
      and that correctly harnessing the system during tuition will lead to educational
      benefits. Various experimental tasks have been used to investigate individuals'
      ANSs, and it has been assumed that these tasks measure the same system. We tested
      the relationship across six measures of the ANS. Surprisingly, despite typical
      performance on each task, adult participants' performances across the tasks were
      not correlated, and estimates of the acuity of individuals' ANSs from different
      tasks were unrelated. These results highlight methodological issues with tasks
      typically used to measure the ANS and call into question claims that individuals
      use a single system to complete all these tasks.

PMID- 21846266
TI  - Expertise and gambling: using type 2 signal detection theory to investigate
      differences between regular gamblers and nongamblers.
AB  - This paper presents an experimental investigation into how individuals make
      decisions under uncertainty when faced with different payout structures in the
      context of gambling. Type 2 signal detection theory was utilized to compare
      sensitivity to bias manipulations between regular nonproblem gamblers and
      nongamblers in a novel probability-based gambling task. The results indicated
      that both regular gamblers and nongamblers responded to the changes of rewards
      for correct responses (Experiment 1) and penalties for errors (Experiment 2) in
      setting their gambling criteria, but that regular gamblers were more sensitive to
      these manipulations of bias. Regular gamblers also set gambling criteria that
      were more optimal. The results are discussed in terms of an expertise
      transference hypothesis.

PMID- 21846267
TI  - Shifting attention among working memory representations: testing cue type,
      awareness, and strategic control.
AB  - It is well known that visual working memory (VWM) performance is modulated by
      attentional cues presented during encoding. Interestingly, retrospective cues
      presented after encoding, but prior to the test phase also improve performance.
      This improvement in performance is termed the retro-cue benefit. We investigated
      whether the retro-cue benefit is sensitive to cue type, whether participants were
      aware of their improvement in performance due to the retro-cue, and whether the
      effect was under strategic control. Experiment 1 compared the potential cueing
      benefits of abrupt onset retro-cues relying on bottom-up attention, number retro
      cues relying on top-down attention, and arrow retro-cues, relying on a mixture of
      both. We found a significant retro-cue effect only for arrow retro-cues. In
      Experiment 2, we tested participants' awareness of their use of the informative
      retro-cue and found that they were aware of their improved performance. In
      Experiment 3, we asked whether participants have strategic control over the retro
      cue. The retro-cue was difficult to ignore, suggesting that strategic control is
      low. The retro-cue effect appears to be within conscious awareness but not under
      full strategic control.

PMID- 21846278
TI  - Hard work at home: musculoskeletal pain among female homemakers.
AB  - This study explores the relationship between housework and musculoskeletal
      symptoms among homemakers, adjusting for social, demographic and economic
      factors. A cross-sectional survey was carried out on 435 women from Nabaa, a low
      income community in Lebanon. In total, 77% of women reported having
      musculoskeletal pain in the previous 12 months. Both psychosocial and physical
      factors showed significant associations with musculoskeletal symptoms. Related
      psychosocial factors included feelings of stress associated with homemaking and
      homemakers' number of children and self-rated health. The physical factors
      associated with musculoskeletal pain were feeling fatigued at the end of a
      housework day, working long hours and working in awkward postures or frequently
      engaging in repetitive hand movements. Ergonomic stressors were also associated
      with pain in the back and upper and lower extremities. Women from this community
      engage in a large number of hours of housework that, alongside other factors,
      were associated with high prevalence of musculoskeletal pain. PRACTITIONER
      SUMMARY: This study contributes to the literature by studying women's housework
      activities in association with musculoskeletal pain. The role of women in
      homemaking activities is explored together with physical exposures leading to
      reported symptoms. This study adds a perspective of a Middle Eastern context to
      the literature of women's musculoskeletal health.

PMID- 21846279
TI  - Alternative approaches to the design of four-burner stoves.
AB  - The spatial arrangement of stove hotplates and associated controls and linkages
      has been of concern to ergonomists. In this study, two different approaches were
      used to determine preferred arrangements. In the first, one group of participants
      were given locations of controls and asked to place hotplates; a second group was
      given hotplate locations and asked to place controls. In each case, linkages were
      to be indicated. In the second approach, drawings of stove layouts with controls
      and linkages were given. Scales of preference of control/hotplate layouts were
      established. Arrangements having high spatial congruence between hotplate and
      controls were nominated and most preferred by participants in the first approach.
      In the second approach, it was found possible to discriminate between
      arrangements that had high spatial congruence and high compatibility between
      hotplate and control and, hence, to determine 'best' designs in terms of
      participant preferences. STATEMENT OF RELEVANCE: Most research on stove layout
      has been with hotplates in a square arrangement. Two different approaches to
      design show the importance of spatial congruence between hotplate and control for
      obtaining preferred designs having high compatibility, which are superior from an
      ergonomics viewpoint.

PMID- 21846281
TI  - Relationship between prolonged standing and symptoms of varicose veins and
      nocturnal leg cramps among women and men.
AB  - The relationships between occupational characteristics and symptoms of varicose
      veins and nocturnal leg cramps and their gender differences were explored in a
      Korean population. The study population was 2165 workers from various occupations
      (55.6% female). Multiple logistic regression analyses were conducted to reveal
      factors related to symptoms of varicose veins and nocturnal leg cramps. The
      prevalence of varicose veins and nocturnal leg cramps was higher among women than
      men. The characteristics of standing work were different according to gender. In
      gender stratified analysis, the odds ratio of varicose veins was significantly
      high for prolonged standing for male and female workers. However, the odds ratio
      of nocturnal leg cramps was only significant among prolonged standing male
      workers. The models including gender, prolonged standing and occupations in this
      order presented that gender is not significantly associated with varicose veins
      after occupations were added to the model. Prolonged standing at work may be a
      more important risk factor for varicose veins and nocturnal leg cramps than
      biological differences between women and men. Therefore, effective interventions
      to interrupt or reduce prolonged standing at work should be implemented for the
      prevention of varicose veins and nocturnal leg cramps. PRACTITIONER SUMMARY: This
      paper shows associations between occupational characteristics and symptoms of
      varicose veins and nocturnal leg cramps and their gender differences. These
      findings will contribute to knowledge of gender-specific occupational risk
      factors for symptoms in the distal lower extremities.

PMID- 21846282
TI  - Cognitive task demands, self-control demands and the mental well-being of office
      workers.
AB  - The cognitive task demands of office workers and the self-control demands of
      their work roles were measured in a sample of 196 employees in two different
      office layouts using a self-report questionnaire, which was circulated
      electronically. Multiple linear regression analysis revealed that both factors
      were associated with mental well-being, but not with physical well-being, while
      controlling for exposure to psychosocial stressors. The interaction between
      cognitive task demands and self-control demands had the strongest association
      with mental well-being, suggesting that the deleterious effect of one was greater
      when the other was present. An exploratory analysis revealed that the association
      was stronger for employees working in a large open-plan office than for those
      working in smaller offices with more privacy. Frustration of work goals was the
      cognitive task demand having the strongest negative impact on mental well-being.
      Methodological limitations and scale psychometrics (particularly the use of the
      NASA Task Load Index) are discussed. STATEMENT OF RELEVANCE: Modern office work
      has high mental demands and low physical demands and there is a need to design
      offices to prevent adverse psychological reactions. It is shown that cognitive
      task demands interact with self-control demands to degrade mental well-being. The
      association was stronger in an open-plan office.

PMID- 21846283
TI  - The effect of flooring on musculoskeletal symptoms in the lower extremities and
      low back among female nursing assistants.
AB  - This study examines the effect of changing the floor from a 2-mm homogenous vinyl
      floor to a 4-mm heterogeneous vinyl floor (1.5-mm wear layer and 2.5-mm foam
      layer) on musculoskeletal symptoms in the lower extremities and low back among
      nursing assistants in a geriatric care centre. A pre-post design with a reference
      group consisting of nursing assistants from a similar geriatric care centre was
      used. Follow-up measurements were carried out 12 and 24 months after the
      intervention by means of questionnaires. At the 1-year follow-up, the pain
      intensity score in the feet of the intervention group had decreased compared with
      the baseline value and remained statistically significant at the 2-year follow
      up. The decrease in pain intensity score of the feet in the intervention group
      was statistically significantly different from the reference group, both after 1
      and 2 years. PRACTITIONER SUMMARY: The results show the importance of flooring in
      the workplace with regard to reducing musculoskeletal symptoms. Appropriate
      flooring is especially important in the female-dominated health care sector,
      where workers must stand or walk for long periods.

PMID- 21846284
TI  - Risk of musculoskeletal injury among cleaners during vacuuming.
AB  - This study aimed to examine the risk of work-related upper-limb musculoskeletal
      disorders in cleaning workers during the work task of vacuuming. In total, 24
      cleaning workers were observed while they performed vacuum cleaning tasks in the
      normal course of their employment in government schools, hospitality and
      commercial office space sectors. Risk of upper-limb musculoskeletal disorders
      were rated using three observational assessment tools: Manual Task Risk
      Assessment (ManTRA); Quick Exposure Check (QEC); the Rapid Upper Limb Assessment
      (RULA). Mean results (e.g. ManTRA wrist/hand cumulative wrist score 18.67 +/-
      1.27, QEC neck score 13 +/- 1.77, RULA score 6.54 +/- 0.509) demonstrated that
      cleaning workers who perform the task of vacuum cleaning are at risk of work
      related upper-limb musculoskeletal injury, regardless of whether they use a back
      pack or canister machine. Government school cleaners experienced greater risk of
      work-related upper-limb musculoskeletal disorders than workers in either the
      hospitality or commercial office space sectors. PRACTITIONER SUMMARY: Cleaning
      workers in Australia are mostly female, ageing and of non-English-speaking
      backgrounds and involved in repetitive manual tasks. Their occupation is low
      status. This research confirms that vacuuming tasks are a risk for cleaning
      workers and highlights the need for further research to improve conditions for
      these workers.

PMID- 21846285
TI  - A critical review on physical factors and functional characteristics that may
      explain a sex/gender difference in work-related neck/shoulder disorders.
AB  - The objective of this paper is to critically review recent literature on physical
      and functional sex/gender (s/g) differences, with focus on physical determinants
      associated with neck/shoulder musculoskeletal injuries. It is well known that
      there are s/g differences in anthropometrical and functional body characteristics
      (e.g. size and strength). However, s/g differences may be wrongly attributed if
      data analysis does not include appropriate corrections (e.g. by strength for
      endurance). Recent literature on motor control shows that there may indeed be s/g
      differences in muscle coordination and movement strategies during upper limb
      tasks that are not currently explained by methodological inadequacies. Moreover,
      recent studies have shown differences between men and women in sensory
      hypersensitivity characteristics associated with neck/shoulder injuries. Taken
      together, the literature points to the importance of accounting for possible s/g
      differences at all levels of the biopsychosocial system in order to better
      understand sex- and gender-specific issues relevant to workplace health.
      PRACTITIONER SUMMARY: This article critically reviews recent literature and a
      conceptual model highlighting s/g differences in physical and functional
      characteristics related to neck/shoulder musculoskeletal disorders (NSMSD).
      Findings have implications on understanding how personal factors may affect NSMSD
      risk. With better understanding, practitioners can make more appropriate
      decisions to prevent work-related NSMSD.

PMID- 21846286
TI  - Participation of Danish and immigrant cleaners in a 1-year worksite intervention
      preventing physical deterioration.
AB  - Worksite health promotion is seldom offered to workers who are low-educated and
      multi-ethnic, possibly due to an assumption that they are more reluctant to
      participate. Furthermore, little has been done to promote health at female
      dominated workplaces. The main aim of this study was to investigate differences
      in participation among immigrant and Danish cleaners throughout a 1-year
      randomised controlled study tailored to cleaners and carried out in predominantly
      female workplaces. No significant differences in ethnicity were found in consent
      and participation throughout the 1-year intervention. Dropout was equally
      distributed among Danish and immigrant cleaners. This study indicates that a
      worksite health promotion intervention among a female-dominated, high-risk
      occupation such as cleaning can be equally appealing for Danes and immigrants.
      PRACTITIONER SUMMARY: This study provides insight about participation of Danish
      and immigrant cleaners in a worksite health promotion intervention in a
      predominantly female occupation. For attaining high participation and low dropout
      in future worksite health promotion interventions among cleaners, the
      intervention ought to not only target the ethnic background of the workers, but
      also to be specifically tailored to the job group.

PMID- 21846287
TI  - 3-D breast anthropometry of plus-sized women in South Africa.
AB  - Exploratory retail studies in South Africa indicate that plus-sized women
      experience problems and dissatisfaction with poorly fitting bras. The lack of 3-D
      anthropometric studies for the plus-size women's bra market initiated this
      research. 3-D body torso measurements were collected from a convenience sample of
      176 plus-sized women in South Africa. 3-D breast measurements extracted from the
      TC(2) NX12-3-D body scanner 'breast module' software were compared with
      traditional tape measurements. Regression equations show that the two methods of
      measurement were highly correlated although, on average, the bra cup size
      determining factor 'bust minus underbust' obtained from the 3-D method is
      approximately 11% smaller than that of the manual method. It was concluded that
      the total bust volume correlated with the quadrant volume (r = 0.81), cup length,
      bust length and bust prominence, should be selected as the overall measure of
      bust size and not the traditional bust girth and the underbust measurement.
      STATEMENT OF RELEVANCE: This study contributes new data and adds to the knowledge
      base of anthropometry and consumer ergonomics on bra fit and support, published
      in this, the Ergonomics Journal, by Chen et al. (2010) on bra fit and White et
      al. (2009) on breast support during overground running.

PMID- 21846288
TI  - Work organisation and gender among hospital cleaners in Quebec after the merger
      of 'light' and 'heavy' work classifications.
AB  - In Quebec, Canada, cleaning tasks were once divided into 'light' or 'heavy'
      cleaning, assigned respectively to women and men. These categories are being
      merged; in principle, both genders are assigned the same tasks. Activity analysis
      using observations and interviews examined work activity of male and female
      cleaners in two hospitals. In one hospital, work activity could be compared
      before (time 1) and after the work reorganisation (time 2). Some gender
      segregation of tasks appeared to have persisted at time 2, in both hospitals.
      Some route assignments contained components that were difficult for all cleaners,
      especially women of average strength. Only about one-third of the recommendations
      for improvement made at time 1 had been carried out by time 2, 12 years later. In
      a low-status job, it may be hard to meet equality, health and efficiency goals
      because commitment to improving equipment and worksite design may be lacking.
      PRACTITIONER SUMMARY: Current attempts to desegregate jobs should be accompanied
      by attention to physical job demands in order to protect employee health and
      access to equal employment. The study also shows the need to follow up ergonomic
      interventions, particularly in low-status jobs such as cleaning, where
      recommendations can be forgotten.

PMID- 21846289
TI  - Musculoskeletal disorders among female carpet weavers in Iran.
AB  - The aim of this study was to determine factors associated with self-reported
      upper extremity musculoskeletal disorders (UEMSDs) among female carpet weavers.
      Data on demographic characteristics and workplace factors were collected from 626
      female carpet weavers. Type of carpet weaving looms, weaving style (Persian vs.
      Turkish), daily working hours and work experience as well as personal factors
      including age and marital status were significantly and independently associated
      with self-reported UEMSDs (p < 0.05), while education, handedness and weight of
      weaving comb were not. A major finding of this study was the significant
      association between weaving style and UEMSDs. Better measures of the
      biomechanical requirements of carpet weaving tasks in Persian and Turkish weaving
      types are required to understand better their influences on the health of weavers
      and on UEMSDs in particular. Poor workstation design, in particular, design
      inappropriate for the anthropometric dimensions of weavers, was a major risk
      factor for musculoskeletal symptoms in carpet weaving. Therefore, this industry
      should develop equipment adapted to women's sizes and shapes. PRACTITIONER
      SUMMARY: This article provides an insight into the risk factors associated with
      self-reported UEMSDs among female carpet weavers, identifying major factors
      associated with upper extremity musculoskeletal symptoms and exploring guidelines
      for designing weaving workstations.

PMID- 21846290
TI  - A new approach to the measurement of adaptive behavior: development of the PEDI
      CAT for children and youth with autism spectrum disorders.
AB  - The use of current adaptive behavior measures in practice and research is limited
      by their length and need for a professional interviewer. There is a need for
      alternative measures that more efficiently assess adaptive behavior in children
      and youth with autism spectrum disorders (ASDs). The Pediatric Evaluation of
      Disability Inventory-Computer Adaptive Test (PEDI-CAT) is a computer-based
      assessment of a child's ability to perform activities required for personal self
      sufficiency and engagement in the community. This study evaluated the
      applicability, representativeness, and comprehensiveness of the Daily Activity,
      Social/Cognitive, and Responsibility domains for children and youth with an ASD.
      Twenty professionals and 18 parents provided feedback via in-person or virtual
      focus groups and cognitive interviews. Items were perceived to represent relevant
      functional activities within each domain. Child factors and assessment
      characteristics influenced parents' ratings. In response to feedback, 15 items
      and additional directions were added to ensure the PEDI-CAT is a meaningful
      measure when used with this population.

PMID- 21846291
TI  - Immunomodulatory effects induced by cytotoxic T lymphocyte antigen 4
      immunoglobulin with donor peripheral blood mononuclear cell infusion in canine
      major histocompatibility complex-haplo-identical non-myeloablative hematopoietic
      cell transplantation.
AB  - BACKGROUND AIMS. Previously, cytotoxic T lymphocyte antigen 4 (CTLA4)
      immunoglobulin (Ig) has been shown to allow sustained engraftment in dog
      leukocyte antigen (DLA)-identical hematopoietic cell transplant (HCT) after non
      myeloablative conditioning with 100 cGy total body irradiation (TBI). In the
      current study, we investigated the efficacy of pre-transplant CTLA4-Ig in
      promoting engraftment across a DLA-mismatched barrier after non-myeloablative
      conditioning. METHODS. Eight dogs were treated with CTLA4-Ig and donor peripheral
      blood mononuclear cells (PBMC) prior to receiving 200 cGy TBI followed by
      transplantation of granulocyte-colony-stimulating factor (G-CSF) mobilized
      peripheral blood stem cells from DLA haplo-identical littermates with post
      grafting immunosuppression. A control group of six dogs was conditioned with 200
      cGy only and transplanted with grafts from DLA haplo-identical littermates
      followed by post-grafting immunosuppression. RESULTS. In vitro and in vivo donor
      specific hyporesponsiveness was demonstrated on day 0 before TBI in eight dogs
      that received CTLA4-Ig combined with donor PBMC infusions. Four of five dogs
      treated with increased doses of CTLA4-Ig achieved initial engraftment but
      eventually rejected, with a duration of mixed chimerism ranging from 12 to 22
      weeks. CTLA4-Ig did not show any effect on host natural killer (NK) cell function
      in vitro or in vivo. No graft-versus-host disease (GvHD) was observed in dogs
      receiving CTLA4-Ig treatment. CONCLUSIONS. Non-myeloablative conditioning with
      200 cGy TBI and CTLA4-Ig combined with donor PBMC infusion was able to overcome
      the T-cell barrier to achieve initial engraftment without GvHD in dogs receiving
      DLA haplo-identical grafts. However, rejection eventually occurred; we
      hypothesize because of the inability of CTLA4-Ig to abate natural killer cell
      function.

PMID- 21846292
TI  - Mesenchymal stromal cell function is not affected by drugs used in the treatment
      of inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Mesenchymal stromal cells (MSC) have both multilineage
      differentiation capacity and immunosuppressive properties. Promising results with
      MSC administration have been obtained in experimental colitis. Clinical
      application of MSC for the treatment of inflammatory bowel disease (IBD) is
      currently under investigation in phase I-III trials in patients with past or
      concurrent immunomodulating therapy. However, little is known about MSC
      interactions with these immunosuppressive drugs. To address this issue we studied
      the combined effect of MSC and IBD drugs in in vitro functionality assays.
      METHODS: The effects of azathioprine, methotrexate, 6-mercaptopurine and anti
      tumor necrosis factor (TNF)-alpha on MSC phenotype, survival, differentiation
      capacity and immunosuppressive capacity were studied. RESULTS: MSC exposed to
      physiologically relevant concentrations of IBD drugs displayed a normal
      morphology and fulfilled phenotypic and functional criteria for MSC.
      Differentiation into adipocyte and osteocyte lineages was not affected and cells
      exhibited normal survival after exposure to the various drugs. MSC suppression of
      peripheral blood mononuclear cell (PBMC) proliferation in vitro was not hampered
      by IBD drugs. In fact, in the presence of 6-mercaptopurine and anti-TNF-alpha
      antibodies, the inhibitory effect of this drug alone was enhanced, suggesting an
      additive effect of pharmacotherapy and MSC treatment. CONCLUSIONS: This study
      demonstrates that, in vitro, MSC phenotype and function are not affected by
      therapeutic concentrations of drugs commonly used in the treatment of IBD. These
      findings are important for the potential clinical use of MSC in combination with
      immunomodulating drugs and anti-TNF-alpha therapy.

PMID- 21846293
TI  - Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment:
      in vitro and in vivo studies.
AB  - BACKGROUND AIMS: Bone marrow (BM)-derived cells appear to be a promising
      therapeutic source for the treatment of acute myocardial infarction (AMI).
      However, the quantity and quality of the cells to be used, along with the
      appropriate time of administration, still need to be defined. We thus
      investigated the use of BM CD34(+)-derived cells as cells suitable for a cell
      therapy protocol (CTP) in the treatment of experimental AMI. METHODS: The need
      for a large number of cells was satisfied by the use of a previously established
      protocol allowing the expansion of human CD34(+) cells isolated from neonatal and
      adult hematopoietic tissues. We evaluated gene expression, endothelial
      differentiation potential and cytokine release by BM-derived cells during in
      vitro culture. Basal and expanded CD34(+) cells were used as a delivery product
      in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac
      function recovery was evaluated after injecting basal or expanded cells. RESULTS:
      Gene expression analysis of in vitro-expanded cells revealed that endothelial
      markers were up-regulated during culture. Moreover, expanded cells generated a
      CD14(+) subpopulation able to differentiate efficiently into VE-cadherin
      expressing cells. In vivo, we observed a cardiac function recovery in mice
      sequentially treated with basal and expanded cells injected 4 h and 7 days after
      CAL, respectively. CONCLUSIONS: Our data suggest that combining basal and
      expanded BM-derived CD34(+) cells in a specific temporal pattern of
      administration might represent a promising strategy for a successful cell-based
      therapy.

PMID- 21846294
TI  - GATA-4 promotes myocardial transdifferentiation of mesenchymal stromal cells via
      up-regulating IGFBP-4.
AB  - BACKGROUND AIMS: GATA-4 is a cardiac transcription factor and plays an important
      role in cell lineage differentiation during development. We investigated whether
      overexpression of GATA-4 increases adult mesenchymal stromal cell (MSC)
      transdifferentiation into a cardiac phenotype in vitro. METHODS: MSC were
      harvested from rat bone marrow (BM) and transduced with GATA-4 (MSC(GATA-4))
      using a murine stem cell virus (pMSCV) retroviral expression system. Gene
      expression in MSC(GATA-4) was analyzed using quantitative reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting. Native cardiomyocytes
      (CM) were isolated from ventricles of neonatal rats. Myocardial
      transdifferentiation of MSC was determined by immunostaining and
      electrophysiologic recording. The transdifferentiation rate was calculated
      directly from flow cytometery. RESULTS: The expression of cardiac genes,
      including brain natriuretic peptide (BNP), Islet-1 and alpha-sarcomeric actinin
      (alpha-SA), was up-regulated in MSC(GATA-4) compared with control cells that were
      transfected with Green Fluorescent Protein (GFP) only (MSC(Null)). At the same
      time, insulin-like growth factor-binding protein (IGFBP)-4 was significantly up
      regulated in MSC(GATA-4). A synchronous beating of MSC with native CM was
      detected and an action potential was recorded. Some GFP (+) cells were positive
      for alpha-SA staining after MSC were co-cultured with native CM for 7 days. The
      transdifferentiation rate was significantly higher in MSC(GATA-4). Functional
      studies indicated that the differentiation potential of MSC(GATA-4) was decreased
      by knockdown of IGFBP-4. CONCLUSIONS: Overexpression of GATA-4 significantly
      increases MSC differentiation into a myocardial phenotype, which might be
      associated with the up-regulation of IGFBP-4.

PMID- 21846295
TI  - A pilot study of the ability of the forced response test to discriminate between
      3-year-old children with chronic otitis media with effusion or with recurrent
      acute otitis media.
AB  - CONCLUSIONS: When used to test 3-year-old children within 3 months of
      tympanostomy tube placement for recurrent acute otitis media (rAOM) or chronic
      otitis media with effusion (cOME) the forced response test (FRT) showed
      relatively minor differences in the active and passive functions of the
      eustachian tube. While the sample size was small, the high variability in all
      test parameters suggests that the FRT alone is not capable of distinguishing
      between children with different expressions of otitis media. OBJECTIVE: The FRT
      was designed to measure the passive and active properties of the eustachian tube.
      We evaluated the ability of that test to discriminate groups of children with
      rAOM or cOME. METHODS: Twenty-two ears (15 children) with a confirmed history of
      rAOM and 24 ears (17 children) with a confirmed history of cOME were tested at 3
      years of age within 3 months of ventilation tube placement. The parameters of the
      FRT were compared between these groups using a two-tailed Student's t test and
      the frequencies of ears evidencing eustachian tube dilation with swallowing were
      compared between groups using a chi(2) test. RESULTS: Passive resistance and one
      measure of active function were significantly higher in the rAOM group. The
      frequency of tubal dilation was not significantly different between groups. There
      were no differences in any of the FRT measures between cOME ears that did and did
      not have acute otitis media by history.

PMID- 21846296
TI  - Maxillary sinus infundibulum narrowing influences sinus abnormalities in spite of
      the presence or absence of allergy.
AB  - CONCLUSION: Maxillary sinus abnormalities were demonstrated to be associated with
      maxillary sinus infundibulum narrowing as well as nasal airflow resistance
      secondary to nonspecific nasal inflammation. OBJECTIVES: There is no consensus
      regarding the pathogenetic roles of allergy and anatomic variations in sinus
      mucosa abnormalities. We investigated the correlation between allergy and
      anatomic variations in sinus abnormalities in chronic rhinitis patients in the
      presence or absence of allergy. METHODS: In all, 148 adult patients with allergic
      rhinitis (AR) and non-allergic rhinitis (NAR) were enrolled. Opacification of
      sinuses, the size of the maxillary sinus infundibulum, Haller cells, and concha
      bullosa were evaluated based on computed tomography (CT) images. Simultaneously,
      nasal airflow resistance was measured. RESULTS: The AR group comprising 105
      patients showed maxillary sinus opacification in 45 patients. In the NAR group
      including 43 patients, soft tissue opacification was observed in 13 patients.
      There was no significant difference in the incidence of sinus opacification
      between the AR and NAR groups. Both nasal resistance and the infundibulum size in
      both the AR and NAR groups with sinus opacification showed significant
      differences from those without sinus abnormalities. The presence of concha
      bullosa influenced the sinus opacification in both the AR and NAR groups.

PMID- 21846297
TI  - Can we modify transplant outcome by improving lymphocyte recovery?

PMID- 21846298
TI  - Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell
      based interferon-beta gene therapy and cisplatin in a mouse melanoma model.
AB  - BACKGROUND AIMS: Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT
      MSC) represent a novel tool for delivering therapeutic genes to tumor cells.
      Interferon (IFN)-beta is a cytokine with pleiotropic cellular functions,
      including anti-proliferative, immunomodulatory and anti-angiogenic activities.
      The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN
      beta and to evaluate the anti-tumor effect of cAT-MSC-IFN-beta combined with
      cisplatin in mouse melanoma model. METHODS: cAT-MSC engineered to express mouse
      IFN-beta were generated using a lentiviral vector (cAT-MSC-IFN-beta) and the
      secreted IFN-beta-induced inhibition of tumor cell growth and apoptosis on B16F10
      cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse
      was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6
      mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days
      later the engineered cAT-MSC were injected subcutaneously every 3 days to death.
      Tumor volume and survival times were measured. RESULTS: The combination treatment
      of cAT-MSC-IFN-beta with cisplatin was more effective in inhibiting the growth of
      melanoma and resulted in significantly extended survival time than both an
      unengineered cAT-MSC-cisplatin combination group and a cisplatin-alone group.
      Interestingly, subcutaneously injected cAT-MSC-IFN-beta were migrated to tumor
      sites. CONCLUSIONS: Our data suggest that canine AT-MSC could serve as a powerful
      cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions.
      Maximal anti-tumor effects were seen when this therapy was combined with a DNA
      damaging chemotherapeutic agent. This study demonstrates the possible
      applicability of AT-MSC-mediated IFN-beta in treating canine and human cancer
      patients.

PMID- 21846299
TI  - The contractile properties of the medial gastrocnemius motor units innervated by
      L4 and L5 spinal nerves in the rat.
AB  - When a muscle innervation originates from more than one spinal cord segment, the
      injury of one of the respective ventral roots evokes an overload, and alters the
      activity and properties of the remaining motor units. However, it is not well
      documented if the three types of motor units are equally represented within the
      innervating ventral roots. Single motor units in the rat medial gastrocnemius
      muscle were studied and their contractile properties as well as distribution of
      different types of motor units belonging to subpopulations innervated by axons in
      L4 and L5 ventral roots were analyzed. The composition of the three physiological
      types of motor units in the two subpopulations was similar. Force parameters were
      similar for motor units belonging to the two subpopulations. However, the twitch
      time parameters were slightly longer in L4 in comparison to L5 motor units
      although the difference was significant only for fast resistant to fatigue motor
      units. The force-frequency relationships in the two subpopulations of motor units
      were not different. Concluding, the two subpopulations of motor units in the
      studied muscle differ in the number of motor units, but contain similar
      proportions of the three physiological types of these units and their contractile
      properties are similar. Therefore, the injury of one ventral root evokes various
      degrees of muscle denervation, but is non-selective in relation to the three
      types of motor units.

PMID- 21846301
TI  - Characterization of excitatory and inhibitory motor neurons to the human gastric
      clasp and sling fibers.
AB  - The aim of this study was to determine the morphology and position of the
      excitatory and inhibitory motor neurons to the human gastric sling and clasp
      fibers. Motor neurons were identified by retrograde staining with 1,1'-didodecyl
      3,3,3',3'-indocarbocyanine perchlorate (DiI), and choline acetyltransferase
      (ChAT) or nitric oxide synthase (NOS) immunoreactivity was then determined in
      these motor neurons. In the sling preparations, 46% of the DiI-stained cells were
      aboral motor neurons, 43% were local motor neurons, and only 10% were descending
      motor neurons. Overall, 58% were immunoreactive for ChAT, and 36% for NOS (P =
      0.042). Sixty-two percent of local, and 66% of aboral DiI-stained motor neurons
      were immunoreactive for ChAT. In the clasp preparations, 52% of the DiI-stained
      cells were descending motor neurons, 45% were local motor neurons, and only 3%
      were aboral neurons. Overall, 31% were immunoreactive for ChAT and 65% for NOS (P
      = 0.039). Eighty-five percent of the DiI-stained descending motor neurons were
      immunoreactive for NOS. All of the cells that were labeled adequately had a
      single axon and a number of filamentous or flattened lobular dendrites, and
      fitted into the broad category of Dogiel type I neurons. In conclusion, the
      majority of the motor neurons to the sling fibers were ChAT-positive excitatory
      neurons from the myenteric plexus of the stomach and the local region, and to the
      clasp were predominantly NOS-positive inhibitory neurons from the esophagus.

PMID- 21846300
TI  - Recognition memory for vibrotactile rhythms: an fMRI study in blind and sighted
      individuals.
AB  - Calcarine sulcal cortex possibly contributes to semantic recognition memory in
      early blind (EB). We assessed a recognition memory role using vibrotactile
      rhythms and a retrieval success paradigm involving learned "old" and "new"
      rhythms in EB and sighted. EB showed no activation differences in occipital
      cortex indicating retrieval success but replicated findings of somatosensory
      processing. Both groups showed retrieval success in primary somatosensory,
      precuneus, and orbitofrontal cortex. The S1 activity might indicate generic
      sensory memory processes.

PMID- 21846302
TI  - Addressing current medical needs in invasive fungal infection prevention and
      treatment with new antifungal agents, strategies and formulations.
AB  - Introduction: Morbidity and mortality associated with invasive fungal infections
      (IFIs) remains unacceptably high. Such diseases represent a substantial burden to
      the healthcare system. New options are needed to address antifungal resistance in
      existing and emerging pathogens and improve treatment outcomes while minimizing
      drug-related toxicities and interactions. Awareness of new and potential future
      options is of great value for those healthcare professionals who care for
      patients with IFIs. Areas covered: A search of PubMed, infectious diseases
      conference abstracts and reference lists from relevant publications was conducted
      and relevant information abstracted. This review describes the limitations of
      existing systemic antifungal therapies (e.g., resistance, drug-drug interactions,
      drug-related toxicities) and summarizes data regarding several emerging
      antifungal compounds including (but not limited to) new triazoles (e.g.
      isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin Z.
      Agents in clinical trials such as (but not limited to) new triazoles (e.g.,
      isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin
      are included. New formulations of existing drugs including reformulations of
      miconazole, posaconazole and amphotericin B are also reviewed. Finally, new or
      novel administration strategies for existing drugs such as combination antifungal
      therapy, antifungal dose escalation, adjunctive use of iron chelators and
      preemptive therapy are discussed. Expert opinion: All present antifungal agents
      have some deficiencies in antifungal spectra, toxicity, pharmacokinetics and/or
      drug-drug interactions, making them less than ideal for some fungal infections.
      Therefore, there remains an urgent need to find safe, effective, rapidly
      fungicidal, broad-spectrum antifungal agents with excellent pharmacodynamics to
      effectively eliminate the fungus from the body with short antifungal courses.

PMID- 21846303
TI  - Inverted BMI rather than BMI is a better proxy for percentage of body fat.
AB  - BACKGROUND: Percentage of body fat (BF%) is a known risk factor for a range of
      healthcare problems but is difficult to measure. An easy to measure proxy is the
      weight/height(2) ratio known as the Body Mass Index (BMI kg/m(2)). However, BMI
      does have some inherent weaknesses which are readily overcome by its inverse iBMI
      (1000/BMI, cm(2)/kg). METHODS: The association between BF% and both BMI and iBMI
      together with their distributional properties was explored using previously
      published data from healthy (n = 2993) and diseased populations (n = 298).
      RESULTS: BMI is skewed whereas iBMI is symmetrical and so is better approximated
      by the normal distribution. The relationship between BF% and BMI is curved, but
      that of iBMI and BF% is linear and thus iBMI explains more of the variation in
      BF% than BMI. For example a unit increase in BMI for a group of thin women
      represents an increase of 2.3% in BF, but for obese women this represents only a
      0.3% increase in BF-a 7-fold difference. The curvature stems from body mass being
      the numerator in BMI but the denominator in BF% resulting in a form of hyperbolic
      curve which is not the case with iBMI. Furthermore, BMI and iBMI have different
      relationships (interaction) with BF% for men and women, but these differences are
      less marked with iBMI. CONCLUSIONS: Overall, these characteristics of iBMI favour
      its use over BMI, especially in statistical models.

PMID- 21846304
TI  - Failure of college students to complete an online alcohol education course as a
      predictor of high-risk drinking that requires medical attention.
AB  - BACKGROUND: AlcoholEdu(r) for College and other computer-based education programs
      have been developed to reduce alcohol use and related problems among students.
      OBJECTIVES: This study investigated whether the failure of incoming first-year
      students to complete AlcoholEdu predicts future high-risk drinking that requires
      medical attention. METHODS: A review of clinical records kept by a single
      university's health service identified 684 undergraduates (classes of 2007-2011)
      who had presented for an alcohol event (September 2003 through June 2008). We
      used survival analysis to determine whether students who partially completed the
      course or failed to take it were disproportionately represented among student
      patients who presented with elevated blood alcohol concentration (BAC). RESULTS:
      Students who failed to take the online course were 4.64 times more likely than
      those who completed it to experience an alcohol event (p < .0001), while those
      students who had partially completed the course were 1.52 times more likely (p <
      .0001). Amount of online alcohol education and gender were not significantly
      related to students' measured BAC level. CONCLUSION: Students who had completed
      AlcoholEdu were less likely to present for an alcohol event than were students
      who partially completed or failed to take the course. Campus administrators
      should consider whether students who fail to complete an online alcohol course
      should be flagged for more focused interventions (e.g., brief motivational
      interview, mandatory education classes). SCIENTIFIC SIGNIFICANCE: This is the
      first study to show a relationship between first-year college students' non
      completion of an online alcohol course and subsequent high-risk drinking that
      requires medical attention.

PMID- 21846306
TI  - What is rational about killing a patient with an overdose?: enlightenment,
      continental philosophy and the role of the human subject in system failure.
AB  - This paper raises the issue of ergonomics' role in giving primacy to fully
      rational individual human actors in the creation of system failure, despite its
      commitment to see action as constrained by design and operational features of
      work. Reflecting on recent contributions to the journal, ergonomics' dilemma is
      considered against Enlightenment assumptions about individual human reason as the
      route to truth and goodness and its critics in continental philosophy. There is a
      pervasive, unstated pact here. What ergonomics chooses to call certain things
      (violations, errors, non-compliance, situation awareness) not only simultaneously
      affirms and denies full rationality on part of the people it studies, it also
      coincides with what the West sees as scientific, true and instrumental. Thus,
      ergonomics research legitimates its findings in terms it is expected to explain
      itself in. But by doing so, it reproduces the very social order it set out to
      repudiate. Statement of Relevance: Ergonomics' choice of words (violations,
      errors, non-compliance) at once affirms and denies full rationality on part of
      the people it studies, reproducing the very social order it is meant to question
      and change.

PMID- 21846307
TI  - Haptic discrimination of different types of pencils during writing.
AB  - Professional artists seem to develop a preference for certain types of pencils
      and paper (Akyuz 1995 ). While theaesthetic outcome may be the obvious reason for
      this preference, haptic feedback may also play a role in selecting media
      (Prytherch and Jerrard 2001 , 2003 ). This suggestion implies that artists may be
      sensitive to vibrotactile signals resulting from the interaction between pencil
      and paper during drawing. Tribological tests showed that H-range leads generate
      more resistance than B-range pencils when writing on a standard 80 g/m 2 paper.
      Moreover, a constant stimulus 2IFC procedure showed that Fine Arts students found
      it easier to discriminate between H-range and HB than B-range and an HB. This
      suggests that the human haptic system may be sensitive to the vibrotactile
      signals generated by the differences in resistance resulting from the interaction
      of leads with the paper's textured surface. Implications for pencil manufacturing
      and simulations of virtual writing are discussed. Statement of Relevance: The
      study assesses the tactile sensitivity of Fine Artists to the physical properties
      of the interaction between different types of lead and a standard printing paper.
      The results may help in designing more responsive drawing instruments as well as
      more realistic virtual drawing interfaces.

PMID- 21846308
TI  - Effects of heated seat and foot heater on thermal comfort and heater energy
      consumption in vehicle.
AB  - Subjective experiments involving 12 different conditions were conducted to
      investigate the effects of heated seats and foot heaters in vehicles on thermal
      sensation and thermal comfort. The experimental conditions involved various
      combinations of the operative temperature in the test room (10 or 20 degrees C),
      a heated seat (on/off) and a foot heater (room operative temperature +10 or +20
      degrees C). The heated seat and foot heater improved the occupant's thermal
      sensation and comfort in cool environments. The room operative temperature at
      which the occupants felt a 'neutral' overall thermal sensation was decreased by
      about 3 degrees C by using the heated seat or foot heater and by about 6 degrees
      C when both devices were used. Moreover, the effects of these devices on vehicle
      heater energy consumption were investigated using simulations. As a result, it
      was revealed that heated seats and foot heaters can reduce the total heater
      energy consumption of vehicles. Statement of Relevance: Subjective experiments
      were conducted to investigate the effects of heated seats and foot heaters in
      vehicles on thermal comfort. The heated seat and foot heater improved the
      occupant's thermal sensation and comfort in cool environments. These devices can
      reduce the total heater energy consumption in vehicles.

PMID- 21846309
TI  - The impact of map orientation and generalisation on congestion decisions: a
      comparison of schematic-egocentric and topographic-allocentric maps.
AB  - Map information for drivers is usually presented in an allocentric-topographic
      form (as with printed maps) or in an egocentric-schematic form (as with road
      signs). The advent of new variable message boards on UK motorways raises the
      possibility of presenting road maps to reflect congestion ahead. Should these
      maps be allocentric-topographic or egocentric-schematic? This was assessed in an
      eye tracking study, with participants viewing maps of a motorway network in order
      to identify whether any congestion was relevant to their intended route. The
      schematic-egocentric maps were responded to most accurately with shorter fixation
      durations suggesting easier processing. In particular, the driver's entrance and
      intended exit from the map were attended to more in the allocentric maps.
      Individual differences in mental rotation ability also seem to contribute to poor
      performance on allocentric maps. The results favour schematic-egocentric maps for
      roadside congestion information, but also provide theoretical insights into map
      rotation and individual differences. Statement of Relevance: This study informs
      designers and policy makers about optimum representations of traffic congestion
      on roadside variable message signs and, furthermore, demonstrates that individual
      differences contribute to problems with processing certain sign types. Schematic
      egocentric representations of a motorway network produced the best results, as
      noted in behavioural and eye movement measures.

PMID- 21846310
TI  - Effects of menu structure and touch screen scrolling style on the variability of
      glance durations during in-vehicle visual search tasks.
AB  - The effects of alternative navigation device display features on drivers' visual
      sampling efficiency while searching forpoints of interest were studied in two
      driving simulation experiments with 40 participants. Given that the number of
      display items was sufficient, display features that facilitate resumption of
      visual search following interruptions were expected to lead to more consistent in
      vehicle glance durations. As predicted, compared with a grid-style menu,
      searching information in a list-style menu while driving led to smaller variance
      in durations of in-vehicle glances, in particular with nine item displays.
      Kinetic touch screen scrolling induced a greater number of very short in-vehicle
      glances than scrolling with arrow buttons. The touch screen functionality did not
      significantly diminish the negative effects of the grid-menu compared with
      physical controls with list-style menus. The findings suggest that resumability
      of self-paced, in-vehicle visual search tasks could be assessed with the measures
      of variance of in-vehicle glance duration distributions. Statement of Relevance:
      The reported research reveals display design factors affecting safety-relevant
      variability of in-vehicle glance durations and provides a theoretical framework
      for explaining the effects. The research can have a significant methodical value
      for driver distraction research and practical value for the design and testing of
      in-vehicle user interfaces.

PMID- 21846311
TI  - User discomfort, work posture and muscle activity while using a touchscreen in a
      desktop PC setting.
AB  - An experimental study was conducted to evaluate physical risk factors associated
      with the use of touchscreen in a desktop personal computer (PC) setting.
      Subjective rating of visual/body discomfort, shoulder and neck muscle activity,
      elbow movement and user-preferred positions of the workstation were quantified
      from 24 participants during a standardised computer use task with a standard
      keyboard and a mouse (traditional setting), with a touchscreen and the standard
      keyboard (mixed-use condition) and with the touchscreen only. The use of a
      touchscreen was associated with a significant increase of subjective discomfort
      on the shoulder, neck and fingers, myoelectric activity of shoulder and neck
      muscles and percentage of task duration that arms were in the air. Participants
      placed the touchscreen closer and lower when using touch interfaces compared with
      the traditional setting. Results suggest that users would need more frequent
      breaks and proper armrests to reduce physical risks associated with the use of a
      touchscreen in desktop PC settings. Statement of Relevance: In this study,
      subjective discomfort, work posture and muscle activity of touchscreen desktop PC
      users were quantitatively evaluated. The findings of this study can be used to
      understand potential risks from the use of a touchscreen desktop PC and to
      suggest design recommendations for computer workstations with the touchscreen.

PMID- 21846312
TI  - The effects of platform motion and target orientation on the performance of
      trackball manipulation.
AB  - The trackball has been widely employed as a control/command input device on
      moving vehicles, but few studies have explored the effects of platform motion on
      its manipulation. Fewer still have considered this issue in designing the user
      interface and the arrangement of console location and orientation simultaneously.
      This work describes an experiment carried out to investigate the performance of
      trackball users on a simple point-and-click task in a motion simulator. By
      varying the orientation of onscreen targets, the effect of cursor movement
      direction on performance is investigated. The results indicate that the platform
      motion and target orientation both significantly affect the time required to
      point and click, but not the accuracy of target selection. The movement times
      were considerably longer under rolling and pitching motions and for targets
      located along the diagonal axes of the interface. Subjective evaluations carried
      out by the participants agree with these objective results. These findings could
      be used to optimise console and graphical menu design for use on maritime
      vessels. STATEMENT OF RELEVANCE: In military situations, matters of life or death
      may be decided in milliseconds. Any delay or error in classification and
      identification will thus affect the safety of the ship and its crew. This study
      demonstrates that performance of manipulating a trackball is affected by the
      platform motion and target orientation. The results of the present study can
      guide the arrangement of consoles and the design of trackball-based graphical
      user interfaces on maritime vessels.

PMID- 21846313
TI  - Explicit control of adaptive automation under different levels of environmental
      stress.
AB  - This article examines the effectiveness of three different forms of explicit
      control of adaptive automation under low- and high-stress conditions,
      operationalised by different levels of noise. In total, 60 participants were
      assigned to one of three types of automation design (free, prompted and forced
      choice). They were trained for 4 h on a highly automated simulation of a process
      control environment, called AutoCAMS. This was followed by a 4-h testing session
      under noise exposure and quiet conditions. Measures of performance,
      psychophysiology and subjective reactions were taken. The results showed that all
      three modes of explicit control of adaptive automation modes were able to
      attenuate the negative effects of noise. This was partly due to the fact that
      operators opted for higher levels of automation under noise. It also emerged that
      forced choice showed marginal advantages over the two other automation modes.
      Statement of Relevance: This work is relevant to the design of adaptive
      automation since it emphasises the need to consider the impact of work-related
      stressors during task completion. During the presence of stressors, different
      forms of operator support through automation may be required than under more
      favourable working conditions.

PMID- 21846314
TI  - Injury risk associated with physical demands and school environment
      characteristics among a cohort of custodial workers.
AB  - Few epidemiological studies have investigated the relationship between work
      exposures and injury risk among custodians. The relationship between injury risk
      and occupational physical demands (e.g. pushing/pulling, lifting) and school
      environment characteristics (e.g. school type, season) was investigated among a
      cohort of 581 school custodians over a 4-year period. In the final Poisson
      regression models, the risk of injury was associated with time spent in
      pushing/pulling tasks in a dose-response manner increasing to a five-fold risk
      among the highest quartile of exposure (risk ratio = 5.15, 95% CI 1.00, 26.5).
      Injury risk was also associated with working during the school year compared to
      the summer, working in a school with grass vs. gravel grounds and working in a
      school with detached classrooms. Results help to target interventions such as
      alternative methods for floor cleaning to reduce the pushing/pulling demands of
      custodial work and to support decisions for alternatives to detached classrooms
      and grass surfaces. Statement of Relevance: This study examines ergonomic factors
      (physical demand exposures, school environment characteristics) associated with
      injury risk among custodial school workers. The findings help schools to target
      interventions to reduce the physical demands associated with injuries and to
      design school environments to reduce exposures.

PMID- 21846315
TI  - Endocrine regulation of neonatal hypoxia: role of glucose, oxygen, and
      epinephrine supplementation.
AB  - Responses of the endocrine system are vital in revealing the mechanisms of
      respiratory activities. The present study focused on changes in insulin and
      triiodothyronine concentration in serum, its receptors in the hearts of hypoxic
      neonatal rats and glucose, oxygen, and epinephrine resuscitated groups. The
      insulin concentration was significantly increased with a significant upregulation
      of receptors in hypoxic neonates. Triiodothyronine content and its receptors were
      significantly decreased in serum and the hearts of hypoxic neonates. The change
      in hormonal levels is an adaptive modification of the endocrine system to
      encounter the stress. The effectiveness of glucose resuscitation to hypoxic
      neonates was also reported.

PMID- 21846316
TI  - Insulation of tumor suppressor genes by the nuclear factor CTCF.
AB  - One of the most outstanding nuclear factors, which has chromatin insulator and
      transcriptional properties and also contribute to genomic organization, is the
      zinc-finger protein CCCTC-binding factor (CTCF). Among its multiple functions, a
      growing amount of evidence implicates CTCF in the epigenetic regulation of genes
      responsible for the control of the cell cycle, and its mis-regulation can lead to
      aberrant epigenetic silencing of genes involved in cancer development. Detailed
      studies are now revealing that CTCF can serve as a barrier against the spread of
      DNA methylation and histone repressive marks over promoter regions of tumor
      suppressor genes. Moreover, new evidences points out to the capacity of CTCF to
      be covalently modified, in particular, through poly(ADP-ribosyl)ation with
      regulatory consequences. An unexplored aspect of CTCF is its intergenic and
      intragenic distribution in certain loci. Such distribution seems to facilitate
      the formation of an optimal chromatin structure and the recruitment of chromatin
      remodelers with the possible incorporation of RNA polymerase II. Therefore, in
      the context of tumor suppressor genes and cancer development, CTCF appears to
      play a relevant role by incorporating a combination of mechanisms involved in the
      protection against epigenetic silencing components and the maintenance of optimal
      higher-order organization of the corresponding loci.

PMID- 21846317
TI  - Zinc as an appetite stimulator - the possible role of zinc in the progression of
      diseases such as cachexia and sarcopenia.
AB  - Zinc is required by humans and animals for many physiological functions, such as
      growth, immune function, and reproduction. Zinc deficiency induces a number of
      physiological problems, including anorexia, growth retardation, dermatitis, taste
      disorder, and hypogonadism. Although it is clear that zinc deficiency produces
      specific and profound anorexia in experimental animals, the connection between
      zinc deficiency and anorexia is less certain. We were the first to show that
      orally, but not intraperitoneally, administered zinc rapidly stimulates food
      intake through orexigenic peptides coupled to the afferent vagus nerve using rats
      during early-stage zinc deficiency without decreased zinc concentrations in
      plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc
      chloride acutely stimulated food intake after short-term zinc deprivation. We
      also found that orally administered zinc sulfate increased the expression of NPY
      and orexin mRNA after administration. Using vagotomized rats, we tested whether
      the increase in food intake after oral administration of zinc was mediated by the
      vagus nerve. In sham-operated rats, the oral administration of zinc stimulated
      food intake, whereas zinc and saline administrations did not exhibit differing
      effects in vagotomized rats. We conclude that zinc stimulates food intake in
      short-term zinc-deficient rats through the afferent vagus nerve with subsequent
      effects on hypothalamic peptides associated with food intake regulation. In this
      review, we describe recent research investigating the roles of zinc as an
      appetite stimulator in food intake regulation, along with research about
      hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about
      anorexia nervosa, cachexia and sarcopenia. The article also presents some
      promising patents on zinc.

PMID- 21846318
TI  - Mycotoxins detection by chromatography.
AB  - Mycotoxins are metabolites and toxic substances produced by certain filamentous
      fungi that frequently contaminate food and agriculture commodities and it may
      cause disease in animals or humans. The toxigenic fungi are responsible for
      mycotoxin production in food that belongs to mainly three genera: Aspergillus,
      Penicillium and Fusarium. The contamination of food by mycotoxins is difficult to
      control in addition, causing economic impacts on public health, so their
      identification and quantifications are very necessary. Various analytical methods
      are developed for the detection and quantification of mycotoxins in order to
      control the residual contents of these toxins. Among them there is a widely used
      chromatography. This paper reports some chromatographic methods for the detection
      and quantification of mycotoxins described in patents and scientific articles.

PMID- 21846319
TI  - Recent patents in food nanotechnology.
AB  - Nanotechnology is a multidisciplinary field of current interest. The huge
      possibilities in most industries are making nanoscience grow at a rapid pace, but
      what is the real impact of nanotechnology in a traditional industry such as food?
      The study of patents published in the last 20 years provides the answer, and the
      results are quite surprising; the food industry is the fifth largest sector in
      terms of patents related to nanotechnology.

PMID- 21846320
TI  - Recent patents on amylose-flavor inclusion complex nano particles preparation and
      their application.
AB  - Lipophilic and hydrophilic compounds that are solubilized in the form of nano
      sized particles, or "nanoparticles", can be used in pharmacology, in the
      production of food additives, cosmetics, and agriculture, as well as in pet foods
      and veterinary products, amongst other uses. This review focuses on nanoparticles
      and methods for the production of soluble nanoparticles and, in particular,
      inclusion complexes of water-insoluble lipophilic and water-soluble hydrophilic
      organic materials, especially flavor compounds. The host molecule is namely V
      amylose or modified starch molecule, which could form a cavity to fix or secure
      guest molecules. Thus, the V-amylose molecular properties and the molecular
      inclusion complex formation mechanism is firstly introduced, then amylose-other
      ingredients inclusion complex preparation and application are listed, finally
      amylose-flavor molecular inclusion complex preparations and its application have
      been overviewed. Through this review, it is concluded that amylose-small chemical
      molecule inclusion complexes, especially amylose-flavor inclusion complexes have
      a marvelous application prospect and have great significance to develop the nano
      product application field. This paper reviews the recent patents on amylose
      flavour inclusion complex nano particles preparation and their application.

PMID- 21846321
TI  - Recent patents on the sterilization of food and biomaterials by supercritical
      fluids.
AB  - Supercritical fluid technology applies the unique characteristics of certain
      substances under particular conditions of pressure and temperature above their
      critical point. In particular, supercritical fluid sterilization provides a
      nonthermal solution to problems related to bacterial, viral, yeast and enzyme
      inactivation in the food and pharmaceutical industries as well as healthcare
      services. Supercritical fluid CO2 is versatile for sterilization due to its non
      reactive nature, ability to penetrate into cells and tissues, reduced energy
      usage and improved quality retention of heat-sensitive substrates. Therefore, the
      purpose of this review is to illustrate the most recent and related patents for
      sterilizing food and biomaterials with supercritical fluids, published and/or
      granted from 2005 to present. Finally, the manuscript reports a discussion on the
      current challenges and development of supercritical fluid sterilization
      particularly for the food industry.

PMID- 21846322
TI  - Patented techniques for acrylamide mitigation in high-temperature processed
      foods.
AB  - Heating foods has many advantages since it adds taste, color, texture and
      minimizes harmful germs, among others. Flavor and aroma compounds are produced
      via the Maillard reaction, where various hazardous compounds may form as well,
      such as acrylamide. Maillard reaction is believed to be the main route for
      acrylamide formation between reducing sugars (glucose and fructose), sucrose, and
      the amino acid asparagine, and, consequently, a variety of technologies have been
      developed to reduce acrylamide concentration in thermally processed foods based
      either on: (i) Changing process parameters (e.g. time and temperature of cooking)
      which inhibits Maillard Reaction; (ii) Reducing acrylamide precursor levels in
      raw materials to be cooked at high temperatures (e.g. by using microorganisms,
      asparaginase, amino acids and saccharides, blanching, etc.). In this paper, most
      of the recent patents for acrylamide reduction in foods processed at high
      temperatures are mentioned and briefly analyzed in order to develop new
      mitigation techniques for acrylamide in different food matrixes.

PMID- 21846323
TI  - Use of modified atmosphere packaging to preserve mushroom quality during storage.
AB  - Mushrooms have attracted much attention due to their excellent nutritional and
      sensory properties. However, they are highly perishable and rapidly lose their
      organoleptic characteristics. Many methods have been employed for mushroom
      storage, such as packaging, blanching, canning, or freeze drying. Among them,
      modified atmosphere packaging (MAP) has been widely employed for preserving fresh
      mushrooms. MAP provides an affordable packaging system that partly avoids
      enzymatic browning, fermentation and other biochemical processes by maintaining a
      controlled gas atmosphere. Several factors, including optimum CO2 and O2 partial
      pressures, permeability, package material, thickness, or product weight, must be
      considered in order to design a suitable modified atmosphere package for
      mushrooms. Thus, different strategies are available to preserve mushroom quality
      after harvest. The article presents some promising patents on use of modified
      atmosphere packaging to preserve mushroom quality during storage.

PMID- 21846324
TI  - Ligand- and protein-based modeling studies of the inhibitors of human cytochrome
      P450 2D6 and a virtual screening for potential inhibitors from the Chinese herbal
      medicine, Scutellaria baicalensis (Huangqin,Baikal Skullcap).
AB  - We have previously examined the binding patterns of various substrates to human
      cytochrome P450 2D6 (CYP2D6) using a series of molecular modeling methods. In
      this study, we further explored the binding modes of various types of inhibitors
      to CYP2D6 using a combination of ligand- and protein-based modeling approaches.
      Firstly, we developed and validated a pharmacophore model for CYP2D6 inhibitors,
      which consisted of two hydrophobic features and one hydrogen bond acceptor
      feature. Secondly, we constructed and validated a quantitative structure-activity
      relationship (QSAR) model for CYP2D6 inhibitors which gave a poor to moderate
      prediction accuracy. Thirdly, a panel of CYP2D6 inhibitors were subject to
      molecular docking into the active site of wild-type and mutated CYP2D6 enzyme. We
      demonstrated that 8 residues in the active site (Leu213, Glu216, Ser217, Gln244,
      Asp301, Ser304, Ala305, and Phe483) played an important role in the binding to
      the inhibitors via hydrogen bond formation and/or pi-pi stacking interaction.
      Apparent changes in the binding modes of the inhibitors have been observed with
      Phe120Ile, Glu216Asp, Asp301Glu mutations in CYP2D6. Finally, we screened for
      potential binders/inhibitors from the Chinese herbal medicine Scutellaria
      baicalensis (Huangqin, Baikal Skullcap) using the established pharmacophore model
      for CYP2D6 inhibitors and molecular docking approach. Overall, 18 out of 40
      compounds from S. baicalensis were mapped to the pharmacophore model of CYP2D6
      inhibitors and most herbal compounds from S. baicalensis could be docked into the
      active site of CYP2D6. Our study has provided insights into the molecular
      mechanisms of interaction of synthetic and herbal compounds with human CYP2D6 and
      further benchmarking studies are needed to validate our modeling and virtual
      screening results.

PMID- 21846325
TI  - Glycoxidation and wound healing in diabetes: an interesting relationship.
AB  - Impaired diabetic wound healing (WH) constitutes a serious diabetic complication
      with increased morbidity, mortality and health expenditure. The exact
      pathogenetic mechanisms have not been fully clarified. A variety of hyperglycemia
      and oxidative stress related factors, have been proposed, including advanced
      glycaction end products (AGE). The existing literature data, support the role of
      AGE in the pathogenesis of diabetic complications, namely micro- and macro-
      angiopathy which underlie delayed diabetic WH. In addition, a large body of
      evidence support a direct negative effect of AGE in the WH process by their
      interference with various components involved in the cascade following skin
      injury. Endogenously formed or exogenously derived AGE, in a similar manner,
      affect negatively the WH process in diabetes. It is obvious that further studies
      are needed to clarify the exact role of AGE in the impaired diabetic WH and offer
      possible new therapeutic strategies.

PMID- 21846326
TI  - Pharmacological management of type 2 diabetes mellitus: an update.
AB  - While lifestyle modifications and metformin are the cornerstone of the initial
      management of type 2 diabetes mellitus, there is an increasing array of second
      and third-line pharmacological agents for this condition. These include
      sulphonylureas, insulin, thiazolidinediones and alpha-glucosidase inhibitors,
      with the more recent addition of glucagon- like peptide-1 agonists, dipeptidyl
      peptidase-IV inhibitors and pramlintide. Moreover, insulin analogues that better
      simulate endogenous insulin secretion have been developed. This review aims to
      provide an update on the current pharmacological management of type 2 diabetes
      mellitus, and to highlight the benefits and limitations of each treatment.

PMID- 21846327
TI  - Dimerization of MT1-MMP during cellular invasion detected by fluorescence
      resonance energy transfer.
AB  - Homodimerization of the membrane-bound collagenase MT1-MMP [membrane-type 1 MMP
      (matrix metalloproteinase)] is crucial for its collagenolytic activity. However,
      it is not clear whether this dimerization is regulated during cellular invasion
      into three-dimensional collagen matrices. To address this question, we
      established a fluorescence resonance energy transfer system to detect MT1-MMP
      dimerization and analysed the process in cells invading through three-dimensional
      collagen. Our data indicate that dimerization occurs dynamically and constantly
      at the leading edge of migrating cells, but not the trailing edge. We found that
      polarized dimerization was not due to ECM (extracellular matrix) attachment, but
      was rather controlled by reorganization of the actin cytoskeleton by the small
      GTPases, Cdc42 (cell division cycle 42) and Rac1. Our data indicate that cell
      surface collagenolytic activity is regulated co-ordinately with cell migration
      events to enable penetration of the matrix physical barrier.

PMID- 21846329
TI  - Alternative pathways of dehydroascorbic acid degradation in vitro and in plant
      cell cultures: novel insights into vitamin C catabolism.
AB  - L-Ascorbate catabolism involves reversible oxidation to DHA (dehydroascorbic
      acid), then irreversible oxidation or hydrolysis. The precursor-product
      relationships and the identity of several major DHA breakdown products remained
      unclear. In the presence of added H2O2, DHA underwent little hydrolysis to DKG
      (2,3-dioxo-L-gulonate). Instead, it yielded OxT (oxalyl L-threonate), cOxT
      (cyclic oxalyl L-threonate) and free oxalate (~6:1:1), essentially
      simultaneously, suggesting that all three product classes independently arose
      from one reactive intermediate, proposed to be cyclic-2,3-O-oxalyl-L
      threonolactone. Only with plant apoplastic esterases present were the esters
      significant precursors of free oxalate. Without added H2O2, DHA was slowly
      hydrolysed to DKG. Downstream of DKG was a singly ionized dicarboxy compound
      (suggested to be 2-carboxy-L-xylonolactone plus 2-carboxy-L-lyxonolactone), which
      reversibly de-lactonized to a dianionic carboxypentonate. Formation of these
      lactones and acid was minimized by the presence of residual unreacted ascorbate.
      In vivo, the putative 2-carboxy-L-pentonolactones were relatively stable. We
      propose that DHA is a branch-point in ascorbate catabolism, being either oxidized
      to oxalate and its esters or hydrolysed to DKG and downstream carboxypentonates.
      The oxidation/hydrolysis ratio is governed by reactive oxygen species status. In
      vivo, oxalyl esters are enzymatically hydrolysed, but the carboxypentonates are
      stable. The biological roles of these ascorbate metabolites invite future
      exploration.

PMID- 21846328
TI  - Adiponectin inhibits leptin signalling via multiple mechanisms to exert
      protective effects against hepatic fibrosis.
AB  - Adiponectin is protective against hepatic fibrosis, whereas leptin promotes
      fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus
      kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway,
      producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3
      (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B)
      are both negative regulators of JAK/STAT signalling, and recent studies have
      demonstrated a role for adiponectin in regulating SOCS-3 expression. In the
      present study we investigate mechanisms whereby adiponectin dampens leptin
      signalling and prevents excess ECM production. We treated culture-activated rat
      HSCs with recombinant adiponectin, leptin, both or neither, and also treated
      adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon
      tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the
      leptin receptor) phosphorylation, and PTP1B expression and activity. We also
      explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb
      association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb
      phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin
      stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was
      lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R
      association and blocks leptin-stimulated formation of extracellular TIMP-1
      (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1)
      complexes in vitro. These results suggest two novel mechanisms whereby
      adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob
      Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting
      JAK2/STAT3 signalling at multiple points.

PMID- 21846330
TI  - The human Suv3 helicase interacts with replication protein A and flap
      endonuclease 1 in the nucleus.
AB  - The hSuv3 (human Suv3) helicase has been shown to be a major player in
      mitochondrial RNA surveillance and decay, but its physiological role might go
      beyond this functional niche. hSuv3 has been found to interact with BLM (Bloom's
      syndrome protein) and WRN (Werner's syndrome protein), members of the RecQ
      helicase family involved in multiple DNA metabolic processes, and in protection
      and stabilization of the genome. In the present study, we have addressed the
      possible role of hSuv3 in genome maintenance by examining its potential
      association with key interaction partners of the RecQ helicases. By analysis of
      hSuv3 co-IP (co-immunoprecipitation) complexes, we identify two new interaction
      partners of hSuv3: the RPA (replication protein A) and FEN1 (flap endonuclease
      1). Utilizing an in vitro biochemical assay we find that low amounts of RPA
      inhibit helicase activity of hSuv3 on a forked substrate. Another single-strand
      binding protein, mtSSB (mitochondrial single-strand-binding protein), fails to
      affect hSuv3 activity, indicating that the functional interaction is specific for
      hSuv3 and RPA. Further in vitro studies demonstrate that the flap endonuclease
      activity of FEN1 is stimulated by hSuv3 independently of flap length. hSuv3 is
      generally thought to be a mitochondrial helicase, but the physical and functional
      interactions between hSuv3 and known RecQ helicase-associated proteins strengthen
      the hypothesis that hSuv3 may play a significant role in nuclear DNA metabolism
      as well.

PMID- 21846331
TI  - Assessing left ventricular systolic function in shock: evaluation of
      echocardiographic parameters in intensive care.
AB  - INTRODUCTION: Assessing left ventricular (LV) systolic function in a rapid and
      reliable way can be challenging in the critically ill patient. The purpose of
      this study was to evaluate the feasibility and reliability of, as well as the
      association between, commonly used LV systolic parameters, by using serial
      transthoracic echocardiography (TTE). METHODS: Fifty patients with shock and
      mechanical ventilation were included. TTE examinations were performed daily for a
      total of 7 days. Methods used to assess LV systolic function were visually
      estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method,
      mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging
      (TDIs), and velocity time integral in the left ventricular outflow tract (VTI).
      RESULTS: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%,
      99%, 95% and 93%, respectively, of all possible examinations. The correlations
      between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to
      0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed
      substantial variation over time, with the poorest results seen for TDIs and
      AVPDm. The repeatability was best for VTI (interobserver coefficient of variation
      (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively),
      and worst for the Simpson method (8.2% and 10.6%, respectively). CONCLUSIONS:
      EBEF and AVPDm provided the best, and Simpson, the worst feasibility when
      assessing LV systolic function in a population of mechanically ventilated,
      hemodynamically unstable patients. Additionally, the Simpson showed the poorest
      repeatability. We suggest that EBEF can be used instead of single-plane Simpson
      when assessing LV ejection fraction in this category of patients. TDIs and AVPDm,
      as markers of longitudinal function of the LV, are not interchangeable with LV
      ejection fraction.

PMID- 21846332
TI  - Validation and comparison of clinical prediction rules for invasive candidiasis
      in intensive care unit patients: a matched case-control study.
AB  - INTRODUCTION: Due to the increasing prevalence and severity of invasive
      candidiasis, investigators have developed clinical prediction rules to identify
      patients who may benefit from antifungal prophylaxis or early empiric therapy.
      The aims of this study were to validate and compare the Paphitou and Ostrosky
      Zeichner clinical prediction rules in ICU patients in a 689-bed academic medical
      center. METHODS: We conducted a retrospective matched case-control study from May
      2003 to June 2008 to evaluate the sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) of each rule. Cases included
      adults with ICU stays of at least four days and invasive candidiasis matched to
      three controls by age, gender and ICU admission date. The clinical prediction
      rules were applied to cases and controls via retrospective chart review to
      evaluate the success of the rules in predicting invasive candidiasis. Paphitou's
      rule included diabetes, total parenteral nutrition (TPN) and dialysis with or
      without antibiotics. Ostrosky-Zeichner's rule included antibiotics or central
      venous catheter plus at least two of the following: surgery, immunosuppression,
      TPN, dialysis, corticosteroids and pancreatitis. Conditional logistic regression
      was performed to evaluate the rules. Discriminative power was evaluated by area
      under the receiver operating characteristic curve (AUC ROC). RESULTS: A total of
      352 patients were included (88 cases and 264 controls). The incidence of invasive
      candidiasis among adults with an ICU stay of at least four days was 2.3%. The
      prediction rules performed similarly, exhibiting low PPVs (0.041 to 0.054), high
      NPVs (0.983 to 0.990) and AUC ROCs (0.649 to 0.705). A new prediction rule
      (Nebraska Medical Center rule) was developed with PPVs, NPVs and AUC ROCs of
      0.047, 0.994 and 0.770, respectively. CONCLUSIONS: Based on low PPVs and high
      NPVs, the rules are most useful for identifying patients who are not likely to
      develop invasive candidiasis, potentially preventing unnecessary antifungal use,
      optimizing patient ICU care and facilitating the design of forthcoming antifungal
      clinical trials.

PMID- 21846333
TI  - The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non
      mammary cell-autonomous fashion through the immune system and modulates T-cell
      homeostasis and functions.
AB  - INTRODUCTION: Mechanisms underlying low-penetrance, common, non-protein coding
      variants in breast cancer risk loci are largely undefined. We showed previously
      that the non-protein coding mammary carcinoma susceptibility locus Mcs5a/MCS5A
      modulates breast cancer risk in rats and women. The Mcs5a allele from the Wistar
      Kyoto (WKy) rat strain consists of two genetically interacting elements that have
      to be present on the same chromosome to confer mammary carcinoma resistance. We
      also found that the two interacting elements of the resistant allele are required
      for the downregulation of transcript levels of the Fbxo10 gene specifically in T
      cells. Here we describe mechanisms through which Mcs5a may reduce mammary
      carcinoma susceptibility. METHODS: We performed mammary carcinoma multiplicity
      studies with three mammary carcinoma-inducing treatments, namely 7,12
      dimethylbenz(a)anthracene (DMBA) and N-nitroso-N-methylurea (NMU) carcinogenesis,
      and mammary ductal infusion of retrovirus expressing the activated HER2/neu
      oncogene. We used mammary gland and bone marrow transplantation assays to assess
      the target tissue of Mcs5a activity. We used immunophenotyping assays on well
      defined congenic rat lines carrying susceptible and resistant Mcs5a alleles to
      identify changes in T-cell homeostasis and function associated with resistance.
      RESULTS: We show that Mcs5a acts beyond the initial step of mammary epithelial
      cell transformation, during early cancer progression. We show that Mcs5a controls
      susceptibility in a non-mammary cell-autonomous manner through the immune system.
      The resistant Mcs5a allele was found to be associated with an overabundance of gd
      T-cell receptor (TCR)+ T-cells as well as a CD62L (L-selectin)-high population of
      all T-cell classes. In contrast to in mammary carcinoma, gdTCR+ T-cells are the
      predominant T-cell type in the mammary gland and were found to be overabundant in
      the mammary epithelium of Mcs5a resistant congenic rats. Most of them
      simultaneously expressed the CD4, CD8, and CD161alpha markers. In cultured T
      cells of Mcs5a resistant congenic rats we found increased mitogen-induced
      proliferation and production of Th1 cytokines IFNg, IL-2, and Tumor Necrosis
      Factor (TNF), but not Th2 cytokines IL-4 and IL-6, or Th17 cytokine IL-17 when
      compared with susceptible control rats. CONCLUSIONS: These data support a
      hypothesis that Mcs5a displays a non-mammary cell-autonomous mechanism of action
      to modulate breast cancer risk through the immune system. The resistant Mcs5a
      allele is associated with alterations in T-cell homeostasis and functions, and
      overabundance of gammadeltaTCR+ T-cells in carcinogen-exposed mammary epithelium.

PMID- 21846334
TI  - High degree of efficacy in the treatment of cyclic vomiting syndrome with
      combined co-enzyme Q10, L-carnitine and amitriptyline, a case series.
AB  - BACKGROUND: Cyclic vomiting syndrome (CVS), defined by recurrent stereotypical
      episodes of nausea and vomiting, is a relatively-common disabling and
      historically difficult-to-treat condition associated with migraine headache and
      mitochondrial dysfunction. Limited data suggests that the anti-migraine therapies
      amitriptyline and cyproheptadine, and the mitochondrial-targeted cofactors co
      enzyme Q10 and L-carnitine, have efficacy in episode prophylaxis. METHODS: A
      retrospective chart review of 42 patients seen by one clinician that met
      established CVS diagnostic criteria revealed 30 cases with available outcome
      data. Participants were treated on a loose protocol consisting of fasting
      avoidance, co-enzyme Q10 and L-carnitine, with the addition of amitriptyline (or
      cyproheptadine in those < 5 years) in refractory cases. Blood level monitoring of
      the therapeutic agents featured prominently in management. RESULTS: Vomiting
      episodes resolved in 23 cases, and improved by > 75% and > 50% in three and one
      additional case respectively. Among the three treatment failures, two could not
      tolerate amitriptyline (as was also the case in the child with only > 50%
      efficacy) and one had multiple congenital gastrointestinal anomalies. Excluding
      the latter case, substantial efficacy (> 75% response) was 26/29 at the start of
      treatment, and 26/26 in those able to tolerate the regiment, including high
      dosages of amitriptyline. CONCLUSION: Our data suggest that a protocol consisting
      of mitochondrial-targeted cofactors (co-enzyme Q10 and L-carnitine) plus
      amitriptyline (or possibly cyproheptadine in preschoolers) coupled with blood
      level monitoring is highly effective in the prevention of vomiting episodes.

PMID- 21846335
TI  - Calibrating ADL-IADL scales to improve measurement accuracy and to extend the
      disability construct into the preclinical range: a systematic review.
AB  - BACKGROUND: Interest in measuring functional status among nondisabled older
      adults has increased in recent years. This is, in part, due to the notion that
      adults identified as 'high risk' for functional decline portray a state that is
      potentially easier to reverse than overt disability. Assessing relatively healthy
      older adults with traditional self-report measures (activities of daily living)
      has proven difficult because these instruments were initially developed for
      institutionalised older adults. Perhaps less evident, are problems associated
      with change scores and the potential for 'construct under-representation', which
      reflects the exclusion of important features of the construct (e.g., disability).
      Furthermore, establishing a formal hierarchy of functional status tells more than
      the typical simple summation of functional loss, and may have predictive value to
      the clinician monitoring older adults: if the sequence task difficulty is
      accelerated or out of order it may indicate the need for interventions. METHODS:
      This review identified studies that employed item response theory (IRT) to
      examine or revise functional status scales. IRT can be used to transform the
      ordinal nature of functional status scales to interval level data, which serves
      to increase diagnostic precision and sensitivity to clinical change. Furthermore,
      IRT can be used to rank items unequivocally along a hierarchy based on
      difficulty. It should be noted that this review is not concerned with contrasting
      IRT with more traditional classical test theory methodology. RESULTS: A
      systematic search of four databases (PubMed, Embase, CINAHL, and PsychInfo)
      resulted in the review of 2,192 manuscripts. Of these manuscripts, twelve met our
      inclusion/exclusion requirements and thus were targeted for further inspection.
      CONCLUSIONS: Manuscripts presented in this review appear to summarise
      gerontology's best efforts to improve construct validity and content validity
      (i.e., ceiling effects) for scales measuring the early stages of activity
      restriction in community-dwelling older adults. Several scales in this review
      were exceptional at reducing ceiling effects, reducing gaps in coverage along the
      construct, as well as establishing a formal hierarchy of functional decline.
      These instrument modifications make it plausible to detect minor changes in
      difficulty for IADL items positioned at the edge of the disability continuum,
      which can be used to signal the onset of progressive type disability in older
      adults.

PMID- 21846336
TI  - Policy challenges for the pediatric rheumatology workforce: Part I. Education and
      economics.
AB  - For children with rheumatic conditions, the available pediatric rheumatology
      workforce mitigates their access to care. While the subspecialty experiences
      steady growth, a critical workforce shortage constrains access. This three-part
      review proposes both national and international interim policy solutions for the
      multiple causes of the existing unacceptable shortfall. Part I explores the
      impact of current educational deficits and economic obstacles which constrain
      appropriate access to care. Proposed policy solutions follow each identified
      barrier.Challenges consequent to obsolete, limited or unavailable exposure to
      pediatric rheumatology include: absent or inadequate recognition or awareness of
      rheumatic disease; referral patterns that commonly foster delays in timely
      diagnosis; and primary care providers' inappropriate or outdated perception of
      outcomes. Varying models of pediatric rheumatology care delivery consequent to
      market competition, inadequate reimbursement and uneven institutional support
      serve as additional barriers to care.A large proportion of pediatrics residency
      programs offer pediatric rheumatology rotations. However, a minority of
      pediatrics residents participate. The current generalist pediatrician workforce
      has relatively poor musculoskeletal physical examination skills, lacking basic
      competency in musculoskeletal medicine. To compensate, many primary care
      providers rely on blood tests, generating referrals that divert scarce resources
      away from patients who merit accelerated access to care for rheumatic disease.
      Pediatric rheumatology exposure could be enhanced during residency by providing a
      mandatory musculoskeletal medicine rotation that includes related musculoskeletal
      subspecialties. An important step is the progressive improvement of many
      providers' fixed referral and laboratory testing patterns in lieu of sound
      physical examination skills.Changing demographics and persistent reimbursement
      disparities will require workplace innovation and legislative reform.
      Reimbursement reform is utterly essential to extending patient access to
      subspecialty care. In practice settings characterized by a proportion of Medicaid
      subsidized patients in excess of the national average (> 41%), institutional
      support is vital. Accelerating access to care will require the most efficient
      deployment of existing, limited resources. Practice redesign of such resources
      can also improve access, e.g., group appointments and an escalating role for
      physician extenders. Multidisciplinary, team-oriented care and telemedicine have
      growing evidence basis as solutions to limited access to pediatric rheumatology
      services.

PMID- 21846337
TI  - The non-random clustering of non-synonymous substitutions and its relationship to
      evolutionary rate.
AB  - BACKGROUND: Protein sequences are subject to a mosaic of constraint. Changes to
      functional domains and buried residues, for example, are more apt to disrupt
      protein structure and function than are changes to residues participating in
      loops or exposed to solvent. Regions of constraint on the tertiary structure of a
      protein often result in loose segmentation of its primary structure into
      stretches of slowly- and rapidly-evolving amino acids. This clustering can be
      exploited, and existing methods have done so by relying on local sequence
      conservation as a signature of selection to help identify functionally important
      regions within proteins. We invert this paradigm by leveraging the regional
      nature of protein structure and function to both illuminate and make use of
      genome-wide patterns of local sequence conservation. RESULTS: Our hypothesis is
      that the regional nature of structural and functional constraints will assert a
      positive autocorrelation on the evolutionary rates of neighboring sites, which,
      in a pairwise comparison of orthologous proteins, will manifest itself as the
      clustering of non-synonymous changes across the amino acid sequence. We introduce
      a dispersion ratio statistic to test this and related hypotheses. Using genome
      wide interspecific comparisons of orthologous protein pairs, we reveal a strong
      log-linear relationship between the degree of clustering and the intensity of
      constraint. We further demonstrate how this relationship varies with the
      evolutionary distance between the species being compared. We provide some
      evidence that proteins with a history of positive selection deviate from genome
      wide trends. CONCLUSIONS: We find a significant association between the
      evolutionary rate of a protein and the degree to which non-synonymous changes
      cluster along its primary sequence. We show that clustering is a non-redundant
      predictor of evolutionary rate, and we speculate that conflicting signals of
      clustering and constraint may be indicative of a historical period of relaxed
      selection.

PMID- 21846338
TI  - Long-term room temperature preservation of corpse soft tissue: an approach for
      tissue sample storage.
AB  - BACKGROUND: Disaster victim identification (DVI) represents one of the most
      difficult challenges in forensic sciences, and subsequent DNA typing is
      essential. Collected samples for DNA-based human identification are usually
      stored at low temperature to halt the degradation processes of human remains. We
      have developed a simple and reliable procedure for soft tissue storage and
      preservation for DNA extraction. It ensures high quality DNA suitable for PCR
      based DNA typing after at least 1 year of room temperature storage. METHODS:
      Fragments of human psoas muscle were exposed to three different environmental
      conditions for diverse time periods at room temperature. Storage conditions
      included: (a) a preserving medium consisting of solid sodium chloride (salt), (b)
      no additional substances and (c) garden soil. DNA was extracted with proteinase
      K/SDS followed by organic solvent treatment and concentration by centrifugal
      filter devices. Quantification was carried out by real-time PCR using commercial
      kits. Short tandem repeat (STR) typing profiles were analysed with 'expert
      software'. RESULTS: DNA quantities recovered from samples stored in salt were
      similar up to the complete storage time and underscored the effectiveness of the
      preservation method. It was possible to reliably and accurately type different
      genetic systems including autosomal STRs and mitochondrial and Y-chromosome
      haplogroups. Autosomal STR typing quality was evaluated by expert software,
      denoting high quality profiles from DNA samples obtained from corpse tissue
      stored in salt for up to 365 days. CONCLUSIONS: The procedure proposed herein is
      a cost efficient alternative for storage of human remains in challenging
      environmental areas, such as mass disaster locations, mass graves and
      exhumations. This technique should be considered as an additional method for
      sample storage when preservation of DNA integrity is required for PCR-based DNA
      typing.

PMID- 21846339
TI  - Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in
      overweight/obese females.
AB  - BACKGROUND: Fat mass (FM) in overweight/obese subjects has a primary role in
      determining low-grade chronic inflammation and, in turn, insulin resistance (IR)
      and ectopic lipid storage within the liver. Obesity, aging, and FM influence the
      growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation
      might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in
      patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen
      volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could
      affect the IGF-I axis status in overweight/obese, independently of HS. METHODS:
      The study population included 48 overweight/obese women (age 41 +/- 13 years;
      BMI: 35.8 +/- 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting
      plasma glucose and insulin, homeostasis model assessment of insulin resistance
      (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high
      sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF
      I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were
      also calculated. FM was determined by bioelectrical impedance analysis. HS
      severity grading (score 0-4 according liver hyperechogenicity) and spleen
      longitudinal diameter (SLD) were evaluated by ultrasound. RESULTS: Metabolic
      syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS
      prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I
      zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA,
      ALT, CRP, were significantly higher in patients with severe HS than in those with
      mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1
      (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS
      severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS
      severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At
      multivariate analysis the best determinants of IGF-I were FM% (beta = -0.49; p =
      0.001) and IGFBP-1 (beta = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3
      ratio (beta = -0.43; p = 0.004). CONCLUSIONS: The present study suggests that
      lower IGF-I status in our study population is associated with higher FM, SLD, CRP
      and more severe HS.

PMID- 21846340
TI  - A meta-review of evidence on heart failure disease management programs: the
      challenges of describing and synthesizing evidence on complex interventions.
AB  - BACKGROUND: Despite favourable results from past meta-analyses, some recent large
      trials have not found heart failure (HF) disease management programs to be
      beneficial. To explore reasons for this, we evaluated evidence from existing meta
      analyses. METHODS: Systematic review incorporating meta-review was used. We
      selected meta-analyses of randomized controlled trials published after 1995 in
      English that examined the effects of HF disease management programs on key
      outcomes. Databases searched: MEDLINE, EMBASE, Cochrane Database of Systematic
      Reviews (CDSR), DARE, NHS EED, NHS HTA, Ageline, AMED, Scopus, Web of Science and
      CINAHL; cited references, experts and existing reviews were also searched.
      RESULTS: 15 meta-analyses were identified containing a mean of 18.5 randomized
      trials of HF interventions +/- 10.1 (range: 6 to 36). Overall quality of the meta
      analyses was very mixed (Mean AMSTAR Score = 6.4 +/- 1.9; range 2-9). Reporting
      inadequacies were widespread around populations, intervention components,
      settings and characteristics, comparison, and comparator groups. Heterogeneity
      (statistical, clinical, and methodological) was not taken into account
      sufficiently when drawing conclusions from pooled analyses. CONCLUSIONS: Meta
      analyses of heart failure disease management programs have promising findings but
      often fail to report key characteristics of populations, interventions, and
      comparisons. Existing reviews are of mixed quality and do not adequately take
      account of program complexity and heterogeneity.

PMID- 21846341
TI  - Early dissemination of bevacizumab for advanced colorectal cancer: a prospective
      cohort study.
AB  - BACKGROUND: We describe early dissemination patterns for first-line bevacizumab
      given for metastatic colorectal cancer treatment. METHODS: We analyzed patient
      surveys and medical records for a population-based cohort with metastatic
      colorectal cancer treated in multiple regions and health systems in the United
      States (US). Eligible patients were diagnosed with metastatic colorectal cancer
      and initiated first-line chemotherapy after US Food & Drug Administration (FDA)
      bevacizumab approval in February 2004. First-line bevacizumab therapy was defined
      as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic
      colorectal cancer. We evaluated factors associated with first-line bevacizumab
      treatment using logistic regression. RESULTS: Among 355 patients, 31% received
      first-line bevacizumab in the two years after FDA approval, including 26% of men,
      41% of women, and 16% of those >= 75 years. Use rose sharply within 6 months
      after FDA approval, then plateaued. 20% of patients received bevacizumab in
      combination with irinotecan; 53% received it with oxaliplatin. Men were less
      likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p =
      0.026). Patients >= 75 years were less likely to receive bevacizumab than
      patients < 55 years (adjusted OR 0.13; 95% CI 0.04-0.46; p = 0.001). CONCLUSIONS:
      One-third of eligible metastatic colorectal cancer patients received first-line
      bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab
      as part of the regimen used in the pivotal study leading to FDA approval.

PMID- 21846342
TI  - A genetically anchored physical framework for Theobroma cacao cv. Matina 1-6.
AB  - BACKGROUND: The fermented dried seeds of Theobroma cacao (cacao tree) are the
      main ingredient in chocolate. World cocoa production was estimated to be 3
      million tons in 2010 with an annual estimated average growth rate of 2.2%. The
      cacao bean production industry is currently under threat from a rise in fungal
      diseases including black pod, frosty pod, and witches' broom. In order to address
      these issues, genome-sequencing efforts have been initiated recently to
      facilitate identification of genetic markers and genes that could be utilized to
      accelerate the release of robust T. cacao cultivars. However, problems inherent
      with assembly and resolution of distal regions of complex eukaryotic genomes,
      such as gaps, chimeric joins, and unresolvable repeat-induced compressions, have
      been unavoidably encountered with the sequencing strategies selected. RESULTS:
      Here, we describe the construction of a BAC-based integrated genetic-physical map
      of the T. cacao cultivar Matina 1-6 which is designed to augment and enhance
      these sequencing efforts. Three BAC libraries, each comprised of 10* coverage,
      were constructed and fingerprinted. 230 genetic markers from a high-resolution
      genetic recombination map and 96 Arabidopsis-derived conserved ortholog set (COS)
      II markers were anchored using pooled overgo hybridization. A dense tile path
      consisting of 29,383 BACs was selected and end-sequenced. The physical map
      consists of 154 contigs and 4,268 singletons. Forty-nine contigs are genetically
      anchored and ordered to chromosomes for a total span of 307.2 Mbp. The unanchored
      contigs (105) span 67.4 Mbp and therefore the estimated genome size of T. cacao
      is 374.6 Mbp. A comparative analysis with A. thaliana, V. vinifera, and P.
      trichocarpa suggests that comparisons of the genome assemblies of these distantly
      related species could provide insights into genome structure, evolutionary
      history, conservation of functional sites, and improvements in physical map
      assembly. A comparison between the two T. cacao cultivars Matina 1-6 and Criollo
      indicates a high degree of collinearity in their genomes, yet rearrangements were
      also observed. CONCLUSIONS: The results presented in this study are a stand-alone
      resource for functional exploitation and enhancement of Theobroma cacao but are
      also expected to complement and augment ongoing genome-sequencing efforts. This
      resource will serve as a template for refinement of the T. cacao genome through
      gap-filling, targeted re-sequencing, and resolution of repetitive DNA arrays.

PMID- 21846343
TI  - Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among
      disaster medical assistance team members after the Great East Japan Earthquake:
      the APOP randomized controlled trial.
AB  - BACKGROUND: On March 11, 2011, a magnitude 9.0 earthquake, the most powerful ever
      recorded in Japan, and a massive tsunami struck off the coast of the Sanriku
      region. A Disaster Medical Assistance Team, a mobile medical team with
      specialized training that is deployed during the acute phase of a disaster, was
      dispatched to areas with large-scale destruction and multiple injured and sick
      casualties. Previous studies have reported critical incident stress (i.e.
      posttraumatic stress disorder symptoms and depressive symptoms) among rescue
      workers as well as the need for screening and prevention for posttraumatic stress
      disorder. So far we have shown in an open trial that posttraumatic stress
      disorder symptoms in critically injured patients can be reduced by taking omega-3
      fatty acids intended to stimulate hippocampal neurogenesis. METHOD/DESIGN: This
      study is designed to determine the effectiveness of attenuating posttraumatic
      distress with omega-3 polyunsaturated fatty acids among Disaster Medical
      Assistance Team members after the Great East Japan Earthquake, and is named the
      APOP randomized controlled trial which is currently ongoing. First, we will
      provide psycho-education on posttraumatic distress, which is common in responders
      to the Disaster Medical Assistance Team members deployed to the disaster area.
      Second, observational research will be conducted to evaluate critical incident
      stress following the completion of medical activities. Third, team members who
      provide consent to participate in the intervention research will be randomly
      divided into a group given an omega-3 fatty acid supplement and a group not given
      the supplements. Outcome will be evaluated at 12 weeks after the supplements are
      shipped to the team members. DISCUSSION: Measures that address critical incident
      stress in disaster responders are important, but there is no substantial evidence
      that links such measures with prevention of posttraumatic stress disorder. Thus,
      any confirmation through this study that the intake of omega-3 fatty acid
      supplements serves as a simple preventative measure for critical incident stress
      will be of great significance. TRIAL REGISTRATION: UMIN Clinical Trials Registry,
      UMIN000005367.

PMID- 21846344
TI  - Barriers to antiretroviral therapy adherence in rural Mozambique.
AB  - BACKGROUND: HIV is treated as a chronic disease, but high lost-to-follow-up rates
      and poor adherence to medication result in higher mortality, morbidity, and viral
      mutation. Within 18 clinical sites in rural Zambezia Province, Mozambique,
      patient adherence to antiretroviral therapy has been sub-optimal. METHODS: To
      better understand barriers to adherence, we conducted 18 community and clinic
      focus groups in six rural districts. We interviewed 76 women and 88 men, of whom
      124 were community participants (CP; 60 women, 64 men) and 40 were health care
      workers (HCW; 16 women, 24 men) who provide care for those living with HIV.
      RESULTS: While there was some consensus, both CP and HCW provided complementary
      insights. CP focus groups noted a lack of confidentiality and poor treatment by
      hospital staff (42% CP vs. 0% HCW), doubt as to the benefits of antiretroviral
      therapy (75% CP vs. 0% HCW), and sharing medications with family members (66% CP
      vs. 0%HCW). Men expressed a greater concern about poor treatment by HCW than
      women (83% men vs. 0% women). Health care workers blamed patient preference for
      traditional medicine (42% CP vs. 100% HCW) and the side effects of medication for
      poor adherence (8% CP vs. 83% CHW). CONCLUSIONS: Perspectives of CP and HCW
      likely reflect differing sociocultural and educational backgrounds. Health care
      workers must understand community perspectives on causes of suboptimal adherence
      as a first step toward effective intervention.

PMID- 21846346
TI  - Stress induced hypertensive response: should it be evaluated more carefully?
AB  - Various diagnostic methods have been used to evaluate hypertensive patients under
      physical and pharmacological stress. Several studies have shown that exercise
      hypertension has an independent, adverse impact on outcome; however, other
      prognostic studies have shown that exercise hypertension is a favorable
      prognostic indicator and associated with good outcome. Exercise hypertension may
      be encountered as a warning signal of hypertension at rest and future
      hypertensive left ventricular hypertrophy. The results of diagnostic stress tests
      support that hypertensive response to exercise is frequently associated with high
      rate-pressure product in hypertensives. In addition to the observations on high
      rate-pressure product and enhanced ventricular contractility in patients with
      hypertension, evaluation of myocardial contractility by Doppler tissue imaging
      has shown hyperdynamic myocardial function under pharmacological stress. These
      recent quantitative data in hypertensives suggest that hyperdynamic myocardial
      function and high rate-pressure product response to stress may be related to
      exaggerated hypertension, which may have more importance than that it has been
      already given in clinical practice.

PMID- 21846345
TI  - Annelid Distal-less/Dlx duplications reveal varied post-duplication fates.
AB  - BACKGROUND: Dlx (Distal-less) genes have various developmental roles and are
      widespread throughout the animal kingdom, usually occurring as single copy genes
      in non-chordates and as multiple copies in most chordate genomes. While the
      genomic arrangement and function of these genes is well known in vertebrates and
      arthropods, information about Dlx genes in other organisms is scarce. We
      investigate the presence of Dlx genes in several annelid species and examine Dlx
      gene expression in the polychaete Pomatoceros lamarckii. RESULTS: Two Dlx genes
      are present in P. lamarckii, Capitella teleta and Helobdella robusta. The C.
      teleta Dlx genes are closely linked in an inverted tail-to-tail orientation,
      reminiscent of the arrangement of vertebrate Dlx pairs, and gene conversion
      appears to have had a role in their evolution. The H. robusta Dlx genes, however,
      are not on the same genomic scaffold and display divergent sequences, while, if
      the P. lamarckii genes are linked in a tail-to-tail orientation they are a
      minimum of 41 kilobases apart and show no sign of gene conversion. No expression
      in P. lamarckii appendage development has been observed, which conflicts with the
      supposed conserved role of these genes in animal appendage development. These Dlx
      duplications do not appear to be annelid-wide, as the polychaete Platynereis
      dumerilii likely possesses only one Dlx gene. CONCLUSIONS: On the basis of the
      currently accepted annelid phylogeny, we hypothesise that one Dlx duplication
      occurred in the annelid lineage after the divergence of P. dumerilii from the
      other lineages and these duplicates then had varied evolutionary fates in
      different species. We also propose that the ancestral role of Dlx genes is not
      related to appendage development.

PMID- 21846347
TI  - Uneventful octreotide LAR therapy throughout three pregnancies, with favorable
      delivery and anthropometric measures for each newborn: a case report.
AB  - INTRODUCTION: The safety of octreotide use, in its short-acting preparation, in
      pregnancy is still unclear. This report provides the first documentation of
      uneventful octreotide LAR use during three pregnancies in a woman with bronchial
      carcinoid-associated adrenocorticotropic hormone-dependent Cushing's syndrome.
      CASE PRESENTATION: A 25-year-old Arabic woman presented to our emergency
      department with rapid onset of headache, flaring acne and hirsutism, facial
      puffiness, weight gain and paroxysmal myopathy, and paranoiac thoughts of rape
      and sexual intimidation. After undergoing surgical removal of a mass by left
      lower lung lobectomy, her residual lung disease medical therapy failed. Chronic
      octreotide LAR injections were initiated as indicated by a positive
      octreoscan.Follow-up revealed a long-lasting positive response to octreotide.
      Avidity of octreotide to somatostatin receptor sub-type 2 was later confirmed by
      a positive somatostatin receptor sub-type 2 in the resected tumor specimen.
      Against our instructions, the patient had three spontaneous pregnancies leading
      to delivery of three full-term healthy children while her octreotide LAR therapy
      continued. CONCLUSION: This case adds more data supporting the potential for the
      safe use of octreotide and the feasibility of octreotide LAR use during
      pregnancy, making compliance with the patient's preference not to withdraw
      octreotide therapy as soon as her pregnancy is confirmed a thoughtful option.

PMID- 21846348
TI  - Trends in induced abortion among Nordic women aged 40-44 years.
AB  - OBJECTIVES: Women aged 40-44 years in 2005 ought to have been subjected to much
      more influence on attitudes and knowledge on contraceptive methods during their
      fertile period than women who were in the same age span in 1975 when the abortion
      laws were introduced. MATERIAL: From official statistics, the rates of induced
      abortion and birth rates in women aged 40-44 years were collected for Sweden,
      Denmark, Norway and Finland for each five-year during the period 1975-2005.
      RESULTS: With the exception of Sweden all other studied Scandinavian countries
      have lowered their abortion rates since 1975 (p<0.001) and reduced the proportion
      of induced abortions in relation to birth rate (p<0.001). In 2005 these countries
      also had lower rates of induced abortion than Sweden in the age group 40-44 years
      (p<0.001). CONCLUSION: There is a significant change in rates of induced abortion
      in women aged 40-44 years in Finland, Norway, Denmark, and at status quo in
      Sweden. 40-44 years in Finland, Norway, Denmark, and at status quo in Sweden.
      This indicates that family planning programs works well in the Nordic countries.
      The differences found may be assumed to possible diverging focus on attitudes or
      ethical considerations.

PMID- 21846349
TI  - Questions asked and answered in pilot and feasibility randomized controlled
      trials.
AB  - BACKGROUND: In the last decade several authors have reviewed the features of
      pilot and feasibility studies and advised on the issues that should be addressed
      within them. We extend this literature by examining published pilot/feasibility
      trials that incorporate random allocation, examining their stated objectives,
      results presented and conclusions drawn, and comparing drug and non-drug trials.
      METHODS: A search of EMBASE and MEDLINE databases for 2000 to 2009 revealed 3652
      papers that met our search criteria. A random sample of 50 was selected for
      detailed review. RESULTS: Most of the papers focused on efficacy: those reporting
      drug trials additionally addressed safety/toxicity; while those reporting non
      drug trials additionally addressed methodological issues. In only 56% (95%
      confidence intervals 41% to 70%) were methodological issues discussed in
      substantial depth, 18% (95% confidence interval 9% to 30%) discussed future
      trials and only 12% (95% confidence interval 5% to 24%) of authors were actually
      conducting one. CONCLUSIONS: Despite recent advice on topics that can
      appropriately be described as pilot or feasibility studies the large majority of
      recently published papers where authors have described their trial as a pilot or
      addressing feasibility do not primarily address methodological issues preparatory
      to planning a subsequent study, and this is particularly so for papers reporting
      drug trials. Many journals remain willing to accept the pilot/feasibility
      designation for a trial, possibly as an indication of inconclusive results or
      lack of adequate sample size.

PMID- 21846350
TI  - A novel amniote model of epimorphic regeneration: the leopard gecko, Eublepharis
      macularius.
AB  - BACKGROUND: Epimorphic regeneration results in the restoration of lost tissues
      and structures from an aggregation of proliferating cells known as a blastema.
      Among amniotes the most striking example of epimorphic regeneration comes from
      tail regenerating lizards. Although tail regeneration is often studied in the
      context of ecological costs and benefits, details of the sequence of tissue-level
      events are lacking. Here we investigate the anatomical and histological events
      that characterize tail regeneration in the leopard gecko, Eublepharis macularius.
      RESULTS: Tail structure and tissue composition were examined at multiple days
      following tail loss, revealing a conserved pattern of regeneration. Removal of
      the tail results in a consistent series of morphological and histological events.
      Tail loss is followed by a latent period of wound healing with no visible signs
      of regenerative outgrowth. During this latent period basal cells of the epidermis
      proliferate and gradually cover the wound. An additional aggregation of
      proliferating cells accumulates adjacent to the distal tip of the severed spinal
      cord marking the first appearance of the blastema. Continued growth of the
      blastema is matched by the initiation of angiogenesis, followed by the re
      development of peripheral axons and the ependymal tube of the spinal cord.
      Skeletal tissue differentiation, corresponding with the expression of Sox9, and
      muscle re-development are delayed until tail outgrowth is well underway.
      CONCLUSIONS: We demonstrate that tail regeneration in lizards involves a highly
      conserved sequence of events permitting the establishment of a staging table. We
      show that tail loss is followed by a latent period of scar-free healing of the
      wound site, and that regeneration is blastema-mediated. We conclude that the
      major events of epimorphic regeneration are highly conserved across vertebrates
      and that a comparative approach is an invaluable biomedical tool for ongoing
      regenerative research.

PMID- 21846351
TI  - A high-resolution integrated map of copy number polymorphisms within and between
      breeds of the modern domesticated dog.
AB  - BACKGROUND: Structural variation contributes to the rich genetic and phenotypic
      diversity of the modern domestic dog, Canis lupus familiaris, although compared
      to other organisms, catalogs of canine copy number variants (CNVs) are poorly
      defined. To this end, we developed a customized high-density tiling array across
      the canine genome and used it to discover CNVs in nine genetically diverse dogs
      and a gray wolf. RESULTS: In total, we identified 403 CNVs that overlap 401
      genes, which are enriched for defense/immunity, oxidoreductase, protease,
      receptor, signaling molecule and transporter genes. Furthermore, we performed
      detailed comparisons between CNVs located within versus outside of segmental
      duplications (SDs) and find that CNVs in SDs are enriched for gene content and
      complexity. Finally, we compiled all known dog CNV regions and genotyped them
      with a custom aCGH chip in 61 dogs from 12 diverse breeds. These data allowed us
      to perform the first population genetics analysis of canine structural variation
      and identify CNVs that potentially contribute to breed specific traits.
      CONCLUSIONS: Our comprehensive analysis of canine CNVs will be an important
      resource in genetically dissecting canine phenotypic and behavioral variation.

PMID- 21846352
TI  - Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors.
AB  - BACKGROUND: While influenza vaccination results in protective antibodies against
      primary infections, clearance of infection is primarily mediated through CD8+ T
      cells. Studying the CD8+ T cell response to influenza epitopes is crucial in
      understanding the disease associated morbidity and mortality especially in at
      risk populations such as the elderly. We compared the CD8+ T cell response to
      immunodominant and subdominant influenza epitopes in HLA-A2+ control, adult
      donors, aged 21-42, and in geriatric donors, aged 65 and older. RESULTS: We used
      a novel artificial Antigen Presenting Cell (aAPC) based stimulation assay to
      reveal responses that could not be detected by enzyme-linked immunosorbent spot
      (ELISpot). 14 younger control donors and 12 geriatric donors were enrolled in
      this study. The mean number of influenza-specific subdominant epitopes per
      control donor detected by ELISpot was only 1.4 while the mean detected by aAPC
      assay was 3.3 (p = 0.0096). Using the aAPC assay, 92% of the control donors
      responded to at least one subdominant epitopes, while 71% of control donors
      responded to more than one subdominant influenza-specific response. 66% of
      geriatric donors lacked a subdominant influenza-specific response and 33% of
      geriatric donors responded to only 1 subdominant epitope. The difference in
      subdominant response between age groups is statistically significant (p =
      0.0003). CONCLUSION: Geriatric donors lacked the broad, multi-specific response
      to subdominant epitopes seen in the control donors. Thus, we conclude that aging
      leads to a decrease in the subdominant influenza-specific CTL responses which may
      contribute to the increased morbidity and mortality in older individuals.

PMID- 21846353
TI  - Visual gene developer: a fully programmable bioinformatics software for synthetic
      gene optimization.
AB  - BACKGROUND: Direct gene synthesis is becoming more popular owing to decreases in
      gene synthesis pricing. Compared with using natural genes, gene synthesis
      provides a good opportunity to optimize gene sequence for specific applications.
      In order to facilitate gene optimization, we have developed a stand-alone
      software called Visual Gene Developer. RESULTS: The software not only provides
      general functions for gene analysis and optimization along with an interactive
      user-friendly interface, but also includes unique features such as programming
      capability, dedicated mRNA secondary structure prediction, artificial neural
      network modeling, network & multi-threaded computing, and user-accessible
      programming modules. The software allows a user to analyze and optimize a
      sequence using main menu functions or specialized module windows. Alternatively,
      gene optimization can be initiated by designing a gene construct and configuring
      an optimization strategy. A user can choose several predefined or user-defined
      algorithms to design a complicated strategy. The software provides expandable
      functionality as platform software supporting module development using popular
      script languages such as VBScript and JScript in the software programming
      environment. CONCLUSION: Visual Gene Developer is useful for both researchers who
      want to quickly analyze and optimize genes, and those who are interested in
      developing and testing new algorithms in bioinformatics. The software is
      available for free download at http://www.visualgenedeveloper.net.

PMID- 21846354
TI  - Protein sequence alignment with family-specific amino acid similarity matrices.
AB  - BACKGROUND: Alignment of amino acid sequences by means of dynamic programming is
      a cornerstone sequence comparison method. The quality of alignments produced by
      dynamic programming critically depends on the choice of the alignment scoring
      function. Therefore, for a specific alignment problem one needs a way of
      selecting the best performing scoring function. This work is focused on the issue
      of finding optimized protein family- and fold-specific scoring functions for
      global similarity matrix-based sequence alignment. FINDINGS: I utilize a
      comprehensive set of reference alignments obtained from structural superposition
      of homologous and analogous proteins to design a quantitative statistical
      framework for evaluating the performance of alignment scoring functions in global
      pairwise sequence alignment. This framework is applied to study how existing
      general-purpose amino acid similarity matrices perform on individual protein
      families and structural folds, and to compare them to family-specific and fold
      specific matrices derived in this work. I describe an adaptive alignment
      procedure that automatically selects an appropriate similarity matrix and
      optimized gap penalties based on the properties of the sequences being aligned.
      CONCLUSIONS: The results of this work indicate that using family-specific
      similarity matrices significantly improves the quality of the alignment of
      homologous sequences over the traditional sequence alignment based on a single
      general-purpose similarity matrix. However, using fold-specific similarity
      matrices can only marginally improve sequence alignment of proteins that share
      the same structural fold but do not share a common evolutionary origin. The
      family-specific matrices derived in this work and the optimized gap penalties are
      available at http://taurus.crc.albany.edu/fsm.

PMID- 21846355
TI  - Role of inducible nitric oxide synthase pathway on methotrexate-induced
      intestinal mucositis in rodents.
AB  - BACKGROUND: Methotrexate treatment has been associated to intestinal epithelial
      damage. Studies have suggested an important role of nitric oxide in such injury.
      The aim of this study was to investigate the role of nitric oxide (NO),
      specifically iNOS on the pathogenesis of methotrexate (MTX)-induced intestinal
      mucositis. METHODS: Intestinal mucositis was carried out by three subcutaneous
      MTX injections (2.5 mg/kg) in Wistar rats and in inducible nitric oxide synthase
      knock-out (iNOS-/-) and wild-type (iNOS+/+) mice. Rats were treated
      intraperitoneally with the NOS inhibitors aminoguanidine (AG; 10 mg/Kg) or L-NAME
      (20 mg/Kg), one hour before MTX injection and daily until sacrifice, on the fifth
      day. The jejunum was harvested to investigate the expression of Ki67, iNOS and
      nitrotyrosine by immunohistochemistry and cell death by TUNEL. The neutrophil
      activity by myeloperoxidase (MPO) assay was performed in the three small
      intestine segments. RESULTS: AG and L-NAME significantly reduced villus and crypt
      damages, inflammatory alterations, cell death, MPO activity, and nitrotyrosine
      immunostaining due to MTX challenge. The treatment with AG, but not L-NAME,
      prevented the inhibitory effect of MTX on cell proliferation. MTX induced
      increased expression of iNOS detected by immunohistochemistry. MTX did not cause
      significant inflammation in the iNOS-/- mice. CONCLUSION: These results suggest
      an important role of NO, via activation of iNOS, in the pathogenesis of
      intestinal mucositis.

PMID- 21846356
TI  - Exploring racial/ethnic differences in substance use: a preliminary theory-based
      investigation with juvenile justice-involved youth.
AB  - BACKGROUND: Racial/ethnic differences in representation, substance use, and its
      correlates may be linked to differential long-term health outcomes for justice
      involved youth. Determining the nature of these differences is critical to
      informing more efficacious health prevention and intervention efforts. In this
      study, we employed a theory-based approach to evaluate the nature of these
      potential differences. Specifically, we hypothesized that (1) racial/ethnic
      minority youth would be comparatively overrepresented in the juvenile justice
      system, (2) the rates of substance use would be different across racial/ethnic
      groups, and (3) individual-level risk factors would be better predictors of
      substance use for Caucasian youth than for youth of other racial/ethnic groups.
      METHODS: To evaluate these hypotheses, we recruited a large, diverse sample of
      justice-involved youth in the southwest (N = 651; M age = 15.7, SD = 1.05, range
      = 14-18 years); 66% male; 41% Hispanic, 24% African American, 15% Caucasian, 11%
      American Indian/Alaska Native). All youth were queried about their substance use
      behavior (alcohol, marijuana, tobacco, illicit hard drug use) and individual
      level risk factors (school involvement, employment, self-esteem, level of
      externalizing behaviors). RESULTS: As predicted, racial/ethnic minority youth
      were significantly overrepresented in the juvenile justice system. Additionally,
      Caucasian youth reported the greatest rates of substance use and substance
      related individual-level risk factors. In contrast, African American youth showed
      the lowest rates for substance use and individual risk factors. Contrary to
      predictions, a racial/ethnic group by risk factor finding emerged for only one
      risk factor and one substance use category. CONCLUSIONS: This research highlights
      the importance of more closely examining racial/ethnic differences in justice
      populations, as there are likely to be differing health needs, and subsequent
      treatment approaches, by racial/ethnic group for justice-involved youth.
      Additionally, this study highlights the need for timely, empirically supported
      (developmentally and cross-culturally) substance abuse interventions for all
      justice-involved youth.

PMID- 21846357
TI  - Induction of stromule formation by extracellular sucrose and glucose in epidermal
      leaf tissue of Arabidopsis thaliana.
AB  - BACKGROUND: Stromules are dynamic tubular structures emerging from the surface of
      plastids that are filled with stroma. Despite considerable progress in
      understanding the importance of certain cytoskeleton elements and motor proteins
      for stromule maintenance, their function within the plant cell is still unknown.
      It has been suggested that stromules facilitate the exchange of metabolites
      and/or signals between plastids and other cell compartments by increasing the
      cytosolically exposed plastid surface area but experimental evidence for the
      involvement of stromules in metabolic processes is not available. The frequent
      occurrence of stromules in both sink tissues and heterotrophic cell cultures
      suggests that the presence of carbohydrates in the extracellular space is a
      possible trigger of stromule formation. We have examined this hypothesis with
      induction experiments using the upper epidermis from rosette leaves of
      Arabidopsis thaliana as a model system. RESULTS: We found that the stromule
      frequency rises significantly if either sucrose or glucose is applied to the
      apoplast by vacuum infiltration. In contrast, neither fructose nor sorbitol or
      mannitol are capable of inducing stromule formation which rules out the
      hypothesis that stromule induction is merely the result of changes in the osmotic
      conditions. Stromule formation depends on translational activity in the cytosol,
      whereas protein synthesis within the plastids is not required. Lastly, stromule
      induction is not restricted to the plastids of the upper epidermis but is
      similarly observed also with chloroplasts of the palisade parenchyma.
      CONCLUSIONS: The establishment of an experimental system allowing the
      reproducible induction of stromules by vacuum infiltration of leaf tissue
      provides a suitable tool for the systematic analysis of conditions and
      requirements leading to the formation of these dynamic organelle structures. The
      applicability of the approach is demonstrated here by analyzing the influence of
      apoplastic sugar solutions on stromule formation. We found that only a subset of
      sugars generated in the primary metabolism of plants induce stromule formation,
      which is furthermore dependent on cytosolic translational activity. This suggests
      regulation of stromule formation by sugar sensing mechanisms and a possible role
      of stromules in carbohydrate metabolism and metabolite exchange.

PMID- 21846358
TI  - Fluxomers: a new approach for 13C metabolic flux analysis.
AB  - BACKGROUND: The ability to perform quantitative studies using isotope tracers and
      metabolic flux analysis (MFA) is critical for detecting pathway bottlenecks and
      elucidating network regulation in biological systems, especially those that have
      been engineered to alter their native metabolic capacities. Mathematically, MFA
      models are traditionally formulated using separate state variables for reaction
      fluxes and isotopomer abundances. Analysis of isotope labeling experiments using
      this set of variables results in a non-convex optimization problem that suffers
      from both implementation complexity and convergence problems. RESULTS: This
      article addresses the mathematical and computational formulation of (13)C MFA
      models using a new set of variables referred to as fluxomers. These composite
      variables combine both fluxes and isotopomer abundances, which results in a
      simply-posed formulation and an improved error model that is insensitive to
      isotopomer measurement normalization. A powerful fluxomer iterative algorithm
      (FIA) is developed and applied to solve the MFA optimization problem. For
      moderate-sized networks, the algorithm is shown to outperform the commonly used
      13CFLUX cumomer-based algorithm and the more recently introduced OpenFLUX
      software that relies upon an elementary metabolite unit (EMU) network
      decomposition, both in terms of convergence time and output variability.
      CONCLUSIONS: Substantial improvements in convergence time and statistical quality
      of results can be achieved by applying fluxomer variables and the FIA algorithm
      to compute best-fit solutions to MFA models. We expect that the fluxomer
      formulation will provide a more suitable basis for future algorithms that analyze
      very large scale networks and design optimal isotope labeling experiments.

PMID- 21846359
TI  - CCR5Delta32 variant and cardiovascular disease in patients with rheumatoid
      arthritis: a cohort study.
AB  - INTRODUCTION: The aim of our study was to analyze the influence of the
      CCR5Delta32 polymorphism in the risk of cardiovascular (CV) events and
      subclinical atherosclerosis among patients with rheumatoid arthritis (RA).
      METHODS: A total of 645 patients fulfilling the American Rheumatism Association
      1987 revised classification criteria for RA were studied. Patients were genotyped
      for the CCR5 rs333 polymorphism using predesigned TaqMan assays. Also, HLA DRB1
      genotyping was performed using molecular-based methods. Carotid intima-media
      thickness, flow-mediated endothelium-dependent dilatation (FMD) and endothelium
      independent vasodilatation, which were used as surrogate markers of subclinical
      atherosclerosis, were measured in a subgroup of patients with no clinical CV
      disease. RESULTS: A lower frequency of carriers of the CCR5Delta32 allele among
      patients with CV events (3.4% versus 11.3%, P = 0.025, odds ratio 0.28, 95%
      confidence interval (95% CI) 0.06 to 0.89) was observed. However, after adjusting
      for gender, age at time of RA diagnosis, and the presence of shared epitope,
      rheumatoid factor and classic CV risk factors in the Cox regression analysis,
      this reduction of CV events in CCR5Delta32 allele carriers was slightly outside
      the range of significance (P = 0.097; hazard ratio 0.37 (95% CI 0.12 to 1.19)).
      Carriers of the CCR5Delta32 deletion also showed higher FMD values than the
      remaining patients (CCR5/CCR5Delta32 patients: 7.03% +/- 6.61% versus CCR5/CCR5
      patients: 5.51% +/- 4.66%). This difference was statistically significant when
      analysis of covariance was performed (P = 0.024). CONCLUSIONS: Our results show a
      potential influence of the CCR5Delta32 deletion on the risk of CV disease among
      patients with RA. This may be due to a protective effect of this allelic variant
      against the development of vascular endothelial dysfunction.

PMID- 21846361
TI  - Health related quality of life in patients with anogenital warts.
AB  - INTRODUCTION: The health-related quality-of-life (HRQoL) instruments are an
      important tool for the evaluation of medical outcomes. Sexually transmitted
      diseases (STDs) influence the patients' life. We aimed to evaluate the HRQoL in
      patients with anogenital warts at the time of and 1 month after the diagnosis.
      MATERIALS AND METHODS: We used the short-form (SF)-36 questionnaire to compare
      the HRQoL of 91 patients with anogenital warts to 53 control subjects with the
      same socioeconomic characteristics. RESULTS: There was no statistical difference
      in the overall HRQoL measurement between the anogenital wart patients and
      controls. However, there was an improvement in the scales of vitality (65.22 +/-
      15.70 vs. 69.04 +/- 14.11, respectively; p < 0.05) and mental health (65.00 +/-
      20.09 vs. 69.43 +/- 18.08, respectively; p < 0.05) in anogenital warts patients
      between the time of diagnosis and 1 month later. Furthermore, there was a
      significant deterioration in the scale of social functioning (73.47 +/- 22.18 vs.
      72.89 +/- 19.28, respectively; p < 0.05). The small sample size is a limitation
      of our study. CONCLUSIONS: HRQoL does not appear to be influenced in anogenital
      wart patients, as measured by the generic instrument SF-36. It is therefore
      important to develop specific instruments for the measurement of HRQoL in this
      group of patients.

PMID- 21846360
TI  - Metabolic network reconstruction and genome-scale model of butanol-producing
      strain Clostridium beijerinckii NCIMB 8052.
AB  - BACKGROUND: Solventogenic clostridia offer a sustainable alternative to petroleum
      based production of butanol--an important chemical feedstock and potential fuel
      additive or replacement. C. beijerinckii is an attractive microorganism for
      strain design to improve butanol production because it (i) naturally produces the
      highest recorded butanol concentrations as a byproduct of fermentation; and (ii)
      can co-ferment pentose and hexose sugars (the primary products from
      lignocellulosic hydrolysis). Interrogating C. beijerinckii metabolism from a
      systems viewpoint using constraint-based modeling allows for simulation of the
      global effect of genetic modifications. RESULTS: We present the first genome
      scale metabolic model (iCM925) for C. beijerinckii, containing 925 genes, 938
      reactions, and 881 metabolites. To build the model we employed a semi-automated
      procedure that integrated genome annotation information from KEGG, BioCyc, and
      The SEED, and utilized computational algorithms with manual curation to improve
      model completeness. Interestingly, we found only a 34% overlap in reactions
      collected from the three databases--highlighting the importance of evaluating the
      predictive accuracy of the resulting genome-scale model. To validate iCM925, we
      conducted fermentation experiments using the NCIMB 8052 strain, and evaluated the
      ability of the model to simulate measured substrate uptake and product production
      rates. Experimentally observed fermentation profiles were found to lie within the
      solution space of the model; however, under an optimal growth objective,
      additional constraints were needed to reproduce the observed profiles--suggesting
      the existence of selective pressures other than optimal growth. Notably, a
      significantly enriched fraction of actively utilized reactions in simulations-
      constrained to reflect experimental rates--originated from the set of reactions
      that overlapped between all three databases (P = 3.52 * 10-9, Fisher's exact
      test). Inhibition of the hydrogenase reaction was found to have a strong effect
      on butanol formation--as experimentally observed. CONCLUSIONS: Microbial
      production of butanol by C. beijerinckii offers a promising, sustainable, method
      for generation of this important chemical and potential biofuel. iCM925 is a
      predictive model that can accurately reproduce physiological behavior and provide
      insight into the underlying mechanisms of microbial butanol production. As such,
      the model will be instrumental in efforts to better understand, and metabolically
      engineer, this microorganism for improved butanol production.

PMID- 21846362
TI  - Application of functionalized nanofluid in thermosyphon.
AB  - A water-based functionalized nanofluid was made by surface functionalizing the
      ordinary silica nanoparticles. The functionalized nanofluid can keep long-term
      stability. and no sedimentation was observed. The functionalized nanofluid as the
      working fluid is applied in a thermosyphon to understand the effect of this
      special nanofluid on the thermal performance of the thermosyphon. The experiment
      was carried out under steady operating pressures. The same work was also explored
      for traditional nanofluid (consisting of water and the same silica nanoparticles
      without functionalization) for comparison. Results indicate that a porous
      deposition layer exists on the heated surface of the evaporator during the
      operating process using traditional nanofluid; however, no coating layer exists
      for functionalized nanofluid. Functionalized nanofluid can enhance the
      evaporating heat transfer coefficient, while it has generally no effect on the
      maximum heat flux. Traditional nanofluid deteriorates the evaporating heat
      transfer coefficient but enhances the maximum heat flux. The existence of the
      deposition layer affects mainly the thermal performance, and no meaningful
      nanofluid effect is found in the present study.

PMID- 21846363
TI  - Renin angiotensin system and gender differences in dopaminergic degeneration.
AB  - BACKGROUND: There are sex differences in dopaminergic degeneration. Men are
      approximately two times as likely as premenopausal women of the same age to
      develop Parkinson's disease (PD). It has been shown that the local renin
      angiotensin system (RAS) plays a prominent role in sex differences in the
      development of chronic renal and cardiovascular diseases, and there is a local
      RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin
      via type 1 (AT1) receptors. RESULTS: In the present study, we observed that
      intrastriatal injection of 6-hydroxydopamine induced a marked loss of
      dopaminergic neurons in the substantia nigra of male rats, which was
      significantly higher than the loss induced in ovariectomized female rats given
      estrogen implants (i.e. rats with estrogen). However, the loss of dopaminergic
      neurons was significantly lower in male rats treated with the AT1 antagonist
      candesartan, and similar to that observed in female rats with estrogen. The
      involvement of the RAS in gender differences in dopaminergic degeneration was
      confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP.
      Significantly higher expression of AT1 receptors, angiotensin converting enzyme
      activity, and NADPH-oxidase complex activity, and much lower levels of AT2
      receptors were observed in male rats than in female rats with estrogen.
      CONCLUSIONS: The results suggest that brain RAS plays a major role in the
      increased risk of developing PD in men, and that manipulation of brain RAS may be
      an efficient approach for neuroprotective treatment of PD in men, without the
      feminizing effects of estrogen.

PMID- 21846364
TI  - Idiopathic eosinophilic parotitis in an eight-year-old boy: a case report.
AB  - INTRODUCTION: A number of medical conditions, some of them recently reported, are
      associated with an increased production of eosinophils. We report the first case
      of eosinophilic parotitis in the literature. CASE PRESENTATION: The patient was
      an eight-year-old Caucasian boy who presented with a two-year history of
      recurring acute parotitis with no fever. He had had a total of five episodes with
      no response to antibiotics, but remission had been achieved with oral
      corticosteroid therapy. We performed allergy tests for inhalant and food
      allergens and for haptens, but the results were all negative. The results of
      echography ruled out sialodochitis. Instead, a swab from the parotid duct led to
      the detection of a high number of eosinophils. CONCLUSIONS: This report is first
      in the literature to describe a case of eosinophilic parotitis, and we suggest
      that a cytological assessment, which is quite simple yet rarely used by
      physicians, be performed when patients with parotitis of uncertain origin are
      under evaluation.

PMID- 21846365
TI  - Topographical aspects in the dynamics of sleep homeostasis in young men:
      individual patterns.
AB  - BACKGROUND: Sleep homeostasis refers to the increase of sleep pressure during
      waking and the decrease of sleep intensity during sleep. Electroencephalography
      (EEG) slow-wave activity (SWA; EEG power in the 0.75-4.5 Hz range) is a marker of
      non-rapid eye movement (NREM) sleep intensity and can be used to model sleep
      homeostasis (Process S). SWA shows a frontal predominance, and its increase after
      sleep deprivation is most pronounced in frontal areas. The question arises
      whether the dynamics of the homeostatic Process S also show regional specificity.
      Furthermore, the spatial distribution of SWA is characteristic for an individual
      and may reflect traits of functional anatomy. The aim of the current study was to
      quantify inter-individual variation in the parameters of Process S and
      investigate their spatial distribution. Polysomnographic recordings obtained with
      27 EEG derivations of a baseline night of sleep and a recovery night of sleep
      after 40 h of sustained wakefulness were analyzed. Eight healthy young subjects
      participated in this study. Process S was modeled by a saturating exponential
      function during wakefulness and an exponential decline during sleep. Empirical
      mean SWA per NREM sleep episode at episode midpoint served for parameter
      estimation at each derivation. Time constants were restricted to a
      physiologically meaningful range. RESULTS: For both, the buildup and decline of
      Process S, significant topographic differences were observed: The decline and
      buildup of Process S were slowest in fronto-central areas while the fastest
      dynamics were observed in parieto-occipital (decrease) and frontal (buildup)
      areas. Each individual showed distinct spatial patterns in the parameters of
      Process S and the parameters differed significantly between individuals.
      CONCLUSIONS: For the first time, topographical aspects of the buildup of Process
      S were quantified. Our data provide an additional indication of regional
      differences in sleep homeostasis and support the notion of local aspects of sleep
      regulation.

PMID- 21846366
TI  - Optimality and evolution of transcriptionally regulated gene expression.
AB  - BACKGROUND: How transcriptionally regulated gene expression evolves under natural
      selection is an open question. The cost and benefit of gene expression are the
      driving factors. While the former can be determined by gratuitous induction, the
      latter is difficult to measure directly. RESULTS: We addressed this problem by
      decoupling the regulatory and metabolic function of the Escherichia coli lac
      system, using an inducer that cannot be metabolized and a carbon source that does
      not induce. Growth rate measurements directly identified the induced expression
      level that maximizes the metabolism benefits minus the protein production costs,
      without relying on models. Using these results, we established a controlled
      mismatch between sensing and metabolism, resulting in sub-optimal transcriptional
      regulation with the potential to improve by evolution. Next, we tested the
      evolutionary response by serial transfer. Constant environments showed cells
      evolving to the predicted expression optimum. Phenotypes with decreased
      expression emerged several hundred generations later than phenotypes with
      increased expression, indicating a higher genetic accessibility of the latter.
      Environments alternating between low and high expression demands resulted in
      overall rather than differential changes in expression, which is explained by the
      concave shape of the cross-environmental tradeoff curve that limits the selective
      advantage of altering the regulatory response. CONCLUSIONS: This work indicates
      that the decoupling of regulatory and metabolic functions allows one to directly
      measure the costs and benefits that underlie the natural selection of gene
      regulation. Regulated gene expression is shown to evolve within several hundreds
      of generations to optima that are predicted by these costs and benefits. The
      results provide a step towards a quantitative understanding of the adaptive
      origins of regulatory systems.

PMID- 21846367
TI  - Autophagy in rat annulus fibrosus cells: evidence and possible implications.
AB  - INTRODUCTION: Programmed cell death of intervertebral disc (IVD) cells plays an
      important role in IVD degeneration, but the role of autophagy, a closely related
      cell death event, in IVD cells has not been documented. The current study was
      designed to investigate the effect of interleukin (IL)-1beta on the occurrence of
      autophagy of rat annulus fibrosus (AF) cells and the interrelationship between
      autophagy and apoptosis. METHODS: Rat AF cells were isolated and exposed, in
      tissue cultures with or without serum, to IL-1beta in different concentrations
      for 24 hours. Ultrastructural analysis, flow cytometry and lysosomal activity
      assessment were performed after the in vitro treatment to determine the presence
      and levels of autophagy. The mRNA expression of autophagy-related proteins
      (Beclin-1, Bcl-2 and microtubule associated protein 1 light chain 3 (LC3)) were
      evaluated using real-time PCR. 3-methyladenine (3-MA), a PI3K inhibitor, was used
      to determine the interaction between autophagy and apoptosis via the suppression
      of autophagy. RESULTS: Autophagy was detected in rat AF cells under serum
      starvation condition by transmission electron microscopy. PCR and flow cytometry
      results showed that IL-1beta enhanced the autophagy-induction effect of serum
      deprivation in a dose-dependent manner. However, IL-1beta alone failed to induce
      autophagy in AF cells cultured without serum starvation. When autophagy was
      suppressed by 3-MA, the apoptosis incidence was increased. Serum supplement also
      partly reversed the autophagy incidence without affecting the apoptosis incidence
      in the same cells. CONCLUSIONS: IL-1beta up-regulates serum deprivation-induced
      autophagy of AF cells in a dose-dependent manner. Autophagy may represent a
      protective mechanism against apoptosis in AF cells and IVD degeneration.

PMID- 21846368
TI  - Feasibility and acceptability of ACT for the community case management of malaria
      in urban settings in five African sites.
AB  - BACKGROUND: The community case management of malaria (CCMm) is now an established
      route for distribution of artemisinin-based combination therapy (ACT) in rural
      areas, but the feasibility and acceptability of the approach through community
      medicine distributors (CMD) in urban areas has not been explored. It is estimated
      that in 15 years time 50% of the African population will live in urban areas and
      transmission of the malaria parasite occurs in these densely populated areas.
      METHODS: Pre- and post-implementation studies were conducted in five African
      cities: Ghana, Burkina Faso, Ethiopia and Malawi. CMDs were trained to educate
      caregivers, diagnose and treat malaria cases in < 5-year olds with ACT. Household
      surveys, focus group discussions and in-depth interviews were used to evaluate
      impact. RESULTS: Qualitative findings: In all sites, interviews revealed that
      caregivers' knowledge of malaria signs and symptoms improved after the
      intervention. Preference for CMDs as preferred providers for malaria increased in
      all sites.Quantitative findings: 9001 children with an episode of fever were
      treated by 199 CMDs in the five study sites. Results from the CHWs registers show
      that of these, 6974 were treated with an ACT and 6933 (99%) were prescribed the
      correct dose for their age. Fifty-four percent of the 3,025 children for which
      information about the promptness of treatment was available were treated within
      24 hours from the onset of symptoms.From the household survey 3700 children were
      identified who had an episode of fever during the preceding two weeks. 1480 (40%)
      of them sought treatment from a CMD and 1213 of them (82%) had received an ACT.
      Of these, 1123 (92.6%) were administered the ACT for the correct number of doses
      and days; 773 of the 1118 (69.1%) children for which information about the
      promptness of treatment was available were treated within 24 hours from onset of
      symptoms, and 768 (68.7%) were treated promptly and correctly. CONCLUSIONS: The
      concept of CCMm in an urban environment was positive, and caregivers were
      generally satisfied with the services. Quality of services delivered by CMDs and
      adherence by caregivers are similar to those seen in rural CCMm settings. The
      proportion of cases seen by CMDs, however, tended to be lower than was generally
      seen in rural CCMm. Urban CCMm is feasible, but it struggles against other
      sources of established healthcare providers. Innovation is required by everyone
      to make it viable.

PMID- 21846370
TI  - Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1
      transgenic rats.
AB  - BACKGROUND: Separately, chronic alcohol ingestion and HIV-1 infection are
      associated with severe skeletal muscle derangements, including atrophy and
      wasting, weakness, and fatigue. One prospective cohort study reported that 41% of
      HIV-infected patients met the criteria for alcoholism, however; few reports exist
      on the co-morbid effects of these two disease processes on skeletal muscle
      homeostasis. Thus, we analyzed the atrophic effects of chronic alcohol ingestion
      in HIV-1 transgenic rats and identified alterations to several catabolic and
      anabolic factors. FINDINGS: Relative plantaris mass, total protein content, and
      fiber cross-sectional area were reduced in each experimental group compared to
      healthy, control-fed rats. Alcohol abuse further reduced plantaris fiber area in
      HIV-1 transgenic rats. Consistent with previous reports, gene levels of myostatin
      and its receptor activin IIB were not increased in HIV-1 transgenic rat muscle.
      However, myostatin and activin IIB were induced in healthy and HIV-1 transgenic
      rats fed alcohol for 12 weeks. Catabolic signaling factors such as TGFbeta1,
      TNFalpha, and phospho-p38/total-p38 were increased in all groups compared to
      controls. There was no effect on IL-6, leukemia inhibitory factor (LIF),
      cardiotrophin-1 (CT-1), or ciliary neurotrophic factor (CNTF) in control-fed,
      transgenic rats. However, the co-morbidity of chronic alcohol abuse and HIV-1
      related protein expression decreased expression of the two anabolic factors, CT-1
      and CNTF. CONCLUSIONS: Consistent with previous reports, alcohol abuse
      accentuated skeletal muscle atrophy in an animal model of HIV/AIDS. While some
      catabolic pathways known to drive alcoholic or HIV-1-associated myopathies were
      also elevated in this co-morbid model (e.g., TGFbeta1), consistent expression
      patterns were not apparent. Thus, specific alterations to signaling mechanisms
      such as the induction of the myostatin/activin IIB system or reductions in growth
      factor signaling via CT-1- and CNTF-dependent mechanisms may play larger roles in
      the regulation of muscle mass in alcoholic, HIV-1 models.

PMID- 21846369
TI  - Integrated miRNA and mRNA expression profiling of mouse mammary tumor models
      identifies miRNA signatures associated with mammary tumor lineage.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs involved in
      regulating gene expression and protein translation. miRNA expression profiling of
      human breast cancers has identified miRNAs related to the clinical diversity of
      the disease and potentially provides novel diagnostic and prognostic tools for
      breast cancer therapy. In order to further understand the associations between
      oncogenic drivers and miRNA expression in sub-types of breast cancer, we
      performed miRNA expression profiling on mammary tumors from eight well
      characterized genetically engineered mouse (GEM) models of human breast cancer,
      including MMTV-H-Ras, -Her2/neu, -c-Myc, -PymT, -Wnt1 and C3(1)/SV40 T/t-antigen
      transgenic mice, BRCA1(fl/fl);p53(+/-);MMTV-cre knock-out mice and the
      p53(fl/fl);MMTV-cre transplant model. RESULTS: miRNA expression patterns
      classified mouse mammary tumors according to luminal or basal tumor subtypes.
      Many miRNAs found in luminal tumors are expressed during normal mammary
      development. miR-135b, miR-505 and miR-155 are expressed in both basal human and
      mouse mammary tumors and many basal-associated miRNAs have not been previously
      characterized. miRNAs associated with the initiating oncogenic event driving
      tumorigenesis were also identified. miR-10b, -148a, -150, -199a and -486 were
      only expressed in normal mammary epithelium and not tumors, suggesting that they
      may have tumor suppressor activities. Integrated miRNA and mRNA gene expression
      analyses greatly improved the identification of miRNA targets from potential
      targets identified in silico. CONCLUSIONS: This is the first large-scale miRNA
      gene expression study across a variety of relevant GEM models of human breast
      cancer demonstrating that miRNA expression is highly associated with mammary
      tumor lineage, differentiation and oncogenic pathways.

PMID- 21846372
TI  - Anomalous origin of the left coronary artery from the pulmonary artery associated
      with an accessory atrioventricular pathway and managed successfully with surgical
      and interventional electrophysiological treatment: a case report.
AB  - INTRODUCTION: The combination of anomalous left coronary artery origin from the
      pulmonary artery and an accessory pathway has not been reported previously in the
      medical literature. In medicine, the coexistence of two clinical causes can lead
      to the same clinical findings, and this can make the researcher's attempt to
      distinguish between the two of them and, hence, the correct diagnosis and
      treatment difficult. CASE PRESENTATION: A six-month-old boy from Pakistan was
      brought to our hospital with tachypnea and supraventricular tachycardia and, on
      the basis of echocardiography and multi-slice computed tomography, was diagnosed
      with an anomalous left coronary artery origin from the pulmonary artery. The
      presence of an anomalous left coronary artery origin from the pulmonary artery
      was not initially recognized, and left ventricular dysfunction was considered as
      a result of supraventricular tachycardia. He underwent direct re-implantation of
      the left coronary artery to the aorta using the trapdoor flap technique.
      Recurrent episodes of supraventricular tachycardia resistant to maximal
      pharmacological treatment occurred post-operatively. A left posterolateral
      accessory pathway was successfully ablated by using a trans-septal approach.
      CONCLUSIONS: It should not be forgotten by anyone that many times in medicine
      what seems obvious is not correct. It can be difficult to distinguish two
      clinical entities, and frequently one is considered a result of the other. This
      is the first report of the coexistence of an anomalous left coronary artery
      origin from the pulmonary artery and recurrent supraventricular tachycardia due
      to an accessory pathway in a child that was treated successfully with combined
      surgical and interventional electrophysiological treatment. This case may
      represent a first educational step in the field of congenital heart disease, that
      is, that anomalies such as an anomalous left coronary artery origin from the
      pulmonary artery may be concealed in a child with other serious cardiac problems,
      in this case mitral regurgitation, dilation of the left ventricle, and recurrent
      episodes of tachycardia.

PMID- 21846371
TI  - Reduced viscosity Barley beta-Glucan versus placebo: a randomized controlled
      trial of the effects on insulin sensitivity for individuals at risk for diabetes
      mellitus.
AB  - BACKGROUND: Prior studies suggest soluble fibers may favorably affect
      glucose/insulin metabolism. METHODS: This prospective, randomized, placebo
      controlled, double blind, parallel group trial evaluated 50 generally healthy
      subjects without prior diagnosis of diabetes mellitus (44 completers), who were
      administered beverages containing placebo (control), lower dose (3 g/d), or
      higher dose (6 g/d) reduced viscosity barley beta-glucan (BBG) extract. Subjects
      (68% women) mean age 56 years, Body Mass Index (BMI) 32 kg/m2 and baseline
      fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining
      Therapeutic Lifestyle Changes (TLC) diet and consumed three 11 oz study beverages
      daily with meals for 12 weeks. The four primary study endpoint measures were
      plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing
      (OGTT)]. RESULTS: Compared to placebo, administration of 3 g/d BBG over 12 weeks
      significantly reduced glucose incremental Area Under the Curve (iAUC) measures
      during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as
      well as the related homeostasis model assessment of insulin resistance (HOMA-IR).
      Beverages were generally well tolerated with no serious adverse experiences and
      no significant differences between groups for adverse experiences. Per protocol
      instruction, subjects maintained body weight. CONCLUSIONS: These findings suggest
      6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity
      among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and
      who experience no change in body weight. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01375803.

PMID- 21846373
TI  - Congenital malaria in Uraba, Colombia.
AB  - BACKGROUND: Congenital malaria has been considered a rare event; however, recent
      reports have shown frequencies ranging from 3% to 54.2% among newborns of mothers
      who had suffered malaria during pregnancy. There are only a few references
      concerning the epidemiological impact of this entity in Latin-America and
      Colombia. OBJECTIVE: The aim of the study was to measure the prevalence of
      congenital malaria in an endemic Colombian region and to determine some of its
      characteristics. METHODS: A prospective, descriptive study was carried out in the
      mothers who suffered malaria during pregnancy and their newborns. Neonates were
      clinically evaluated at birth and screened for Plasmodium spp. infection by thick
      smear from the umbilical cord and peripheral blood, and followed-up weekly during
      the first 21 days of postnatal life through clinical examinations and thick
      smears. RESULTS: 116 newborns were included in the study and 80 umbilical cord
      samples were obtained. Five cases of congenital infection were identified (four
      caused by P. vivax and one by P. falciparum), two in umbilical cord blood and
      three in newborn peripheral blood. One case was diagnosed at birth and the others
      during follow-up. Prevalence of congenital infection was 4.3%. One of the
      infected newborns was severely ill, while the others were asymptomatic and
      apparently healthy. The mothers of the newborns with congenital malaria had been
      diagnosed with malaria in the last trimester of pregnancy or during delivery, and
      also presented placental infection. CONCLUSIONS: Congenital malaria may be a
      frequent event in newborns of mothers who have suffered malaria during pregnancy
      in Colombia. An association was found between congenital malaria and the
      diagnosis of malaria in the mother during the last trimester of pregnancy or
      during delivery, and the presence of placental infection.

PMID- 21846374
TI  - Do differences in profiling criteria bias performance measurements? Economic
      profiling of medical clinics under the Korea National Health Insurance program:
      an observational study using claims data.
AB  - BACKGROUND: With a greater emphasis on cost containment in many health care
      systems, it has become common to evaluate each physician's relative resource use.
      This study explored the major factors that influence the economic performance
      rankings of medical clinics in the Korea National Health Insurance (NHI) program
      by assessing the consistency between cost-efficiency indices constructed using
      different profiling criteria. METHODS: Data on medical care benefit costs for
      outpatient care at medical clinics nationwide were collected from the NHI claims
      database. We calculated eight types of cost-efficiency index with different
      profiling criteria for each medical clinic and investigated the agreement between
      the decile rankings of each index pair using the weighted kappa statistic.
      RESULTS: The exclusion of pharmacy cost lowered agreement between rankings to the
      lowest level, and differences in case-mix classification also lowered agreement
      considerably. CONCLUSIONS: A medical clinic may be identified as either cost
      efficient or cost-inefficient, even when using the same index, depending on the
      profiling criteria applied. Whether a country has a single insurance or a
      multiple-insurer system, it is very important to have standardized profiling
      criteria for the consolidated management of health care costs.

PMID- 21846375
TI  - An R package implementation of multifactor dimensionality reduction.
AB  - BACKGROUND: A breadth of high-dimensional data is now available with
      unprecedented numbers of genetic markers and data-mining approaches to variable
      selection are increasingly being utilized to uncover associations, including
      potential gene-gene and gene-environment interactions. One of the most commonly
      used data-mining methods for case-control data is Multifactor Dimensionality
      Reduction (MDR), which has displayed success in both simulations and real data
      applications. Additional software applications in alternative programming
      languages can improve the availability and usefulness of the method for a broader
      range of users. RESULTS: We introduce a package for the R statistical language to
      implement the Multifactor Dimensionality Reduction (MDR) method for nonparametric
      variable selection of interactions. This package is designed to provide an
      alternative implementation for R users, with great flexibility and utility for
      both data analysis and research. The 'MDR' package is freely available online at
      http://www.r-project.org/. We also provide data examples to illustrate the use
      and functionality of the package. CONCLUSIONS: MDR is a frequently-used data
      mining method to identify potential gene-gene interactions, and alternative
      implementations will further increase this usage. We introduce a flexible
      software package for R users.

PMID- 21846376
TI  - A patient presenting with a perivascular epithelioid cell tumor in the broad
      ligament: a case report.
AB  - INTRODUCTION: Perivascular epithelioid cell tumors are a family of rare
      mesenchymal tumors composed of histologically and immunohistochemically
      distinctive perivascular epithelioid cells. They can originate in any visceral
      organ or soft tissue and include a range of lesions such as angiomyolipoma, clear
      cell 'sugar' tumor of the lung, lymphangioleiomyomatosis and clear cell
      myomelanocytic tumors of the falciparum ligament/ligament teres. Due to their
      rarity and varied sites and presentation, management of these tumors remains
      highly challenging. CASE PRESENTATION: A 46-year-old para 2 Caucasian woman
      initially presented to the general surgeons at our hospital in North West London
      with abdominal pain. Laparoscopy revealed a right broad ligament hematoma, which
      was thought to be iatrogenic in origin, from insertion of the Veress needle at
      the time of surgery, and was managed conservatively. Upon her re-presentation two
      months later with severe pain, ultrasound scanning revealed the hematoma had
      increased in size and she underwent a total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. Histology results from necrotic tissue from the hematoma
      led to a diagnosis of perivascular epithelioid cell tumor. She was then referred
      to a tertiary oncology center, where she underwent several further operations in
      an attempt to debulk the tumor for symptomatic relief of her pain, with limited
      success. She is now taking the immunosuppressive drug sirolimus, which has
      produced a modest reduction in tumor size. She is now 47 months on from initial
      presentation. CONCLUSIONS: A literature search has revealed only six other case
      reports of broad ligament perivascular epithelioid cell tumors, with varied
      presentations and management. The longest duration of follow-up was 21 months.
      Only five other cases of perivascular epithelioid cell tumor managed with
      sirolimus have been reported. We therefore feel that this report highlights some
      of the difficulties in diagnosing perivascular epithelioid cell tumors, and sheds
      light on management strategies for a very rare gynecological tumor in addition to
      sharing our experience in the use of sirolimus in its treatment.

PMID- 21846377
TI  - Cardiogenic shock following administration of propofol and fentanyl in a healthy
      woman: a case report.
AB  - INTRODUCTION: Cardiogenic shock is very uncommon in healthy people. The
      differential diagnosis for patients with acute heart failure in previously
      healthy hearts includes acute myocardial infarction and myocarditis. However,
      many drugs can also depress myocardial function. Propofol and fentanyl are
      frequently used during different medical procedures. The cardiovascular
      depressive effect of both drugs has been well established, but the development of
      cardiogenic shock is very rare when these agents are used. CASE PRESENTATION:
      After a minor surgical intervention, a 32-year-old Caucasian woman with no
      significant medical history went into sudden hemodynamic deterioration due to
      acute heart failure. An urgent echocardiogram showed severe biventricular
      dysfunction and an estimated left ventricular ejection fraction of 20%.
      Extracorporeal life support and mechanical ventilation were required. Five days
      later her ventricular function had fully recovered, which allowed the progressive
      withdrawal of medical treatment. Prior to her hospital discharge, cardiac MRI
      showed neither edema nor pathological deposits on the delayed contrast
      enhancement sequences. At her six-month follow-up examination, the patient was
      asymptomatic and did not require treatment. CONCLUSION: Although there are many
      causes of cardiogenic shock, the presence of abrupt hemodynamic deterioration and
      the absence of a clear cause could be related to the use of propofol and
      fentanyl.

PMID- 21846378
TI  - The head-regeneration transcriptome of the planarian Schmidtea mediterranea.
AB  - BACKGROUND: Planarian flatworms can regenerate their head, including a functional
      brain, within less than a week. Despite the enormous potential of these animals
      for medical research and regenerative medicine, the mechanisms of regeneration
      and the molecules involved remain largely unknown. RESULTS: To identify genes
      that are differentially expressed during early stages of planarian head
      regeneration, we generated a de novo transcriptome assembly from more than 300
      million paired-end reads from planarian fragments regenerating the head at 16
      different time points. The assembly yielded 26,018 putative transcripts,
      including very long transcripts spanning multiple genomic supercontigs, and
      thousands of isoforms. Using short-read data from two platforms, we analyzed
      dynamic gene regulation during the first three days of head regeneration. We
      identified at least five different temporal synexpression classes, including
      genes specifically induced within a few hours after injury. Furthermore, we
      characterized the role of a conserved Runx transcription factor, smed-runt-like1.
      RNA interference (RNAi) knockdown and immunofluorescence analysis of the
      regenerating visual system indicated that smed-runt-like1 encodes a
      transcriptional regulator of eye morphology and photoreceptor patterning.
      CONCLUSIONS: Transcriptome sequencing of short reads allowed for the simultaneous
      de novo assembly and differential expression analysis of transcripts,
      demonstrating highly dynamic regulation during head regeneration in planarians.

PMID- 21846379
TI  - The prevalence of mental health problems among users of NHS stop smoking
      services: effects of implementing a routine screening procedure.
AB  - BACKGROUND: Tobacco dependence among people with mental health problems is an
      issue that deserves attention both from a clinical and from a public health
      perspective. Research suggests that Stop Smoking Services often fail to ask
      clients about underlying mental health problems and thus fail to put in place the
      treatment adaptations and liaison procedures often required to meet the needs of
      clients with a mental health condition who want to stop smoking. This study
      assesses the recording of mental health problems in a large NHS stop smoking
      service in England and examines the effect of implementing a short screening
      procedure on recording mental health conditions. METHODS: Treatment records from
      the Stop Smoking Service covering a period of 13 months were audited. The
      prevalence of reported mental health problems in the six month period before the
      implementation of the mental health screening procedure was compared with that of
      the six month period following implementation. The screening procedure was only
      implemented in the support services directly provided by the Stop Smoking
      Service. Comparisons were also made with third-party sections of the service
      where no such screening procedure was introduced. RESULTS: The prevalence of
      reported mental health problems among a total of n = 4999 clients rose from less
      than 1% before implementation of the screening procedure to nearly 12% in the
      period following implementation, with the change being statistically significant.
      No significant rise was observed over the same period in the sections of the
      service where no screening procedure was implemented. CONCLUSIONS: The absence of
      standard procedures to record mental health problems among service users in many
      stop smoking services is currently likely to prevent the detection of co
      morbidity. Implementing a simple screening procedure appears suitable to increase
      the routine recording of mental health problems in a stop smoking service, which
      is an essential step to ensure services can be tailored and delivered
      appropriately to the client group.

PMID- 21846380
TI  - Succinylcholine versus rocuronium for rapid sequence intubation in intensive
      care: a prospective, randomized controlled trial.
AB  - INTRODUCTION: Succinylcholine and rocuronium are widely used to facilitate rapid
      sequence induction (RSI) intubation in intensive care. Concerns relate to the
      side effects of succinylcholine and to slower onset and inferior intubation
      conditions associated with rocuronium. So far, succinylcholine and rocuronium
      have not been compared in an adequately powered randomized trial in intensive
      care. Accordingly, the aim of the present study was to compare the incidence of
      hypoxemia after rocuronium or succinylcholine in critically ill patients
      requiring an emergent RSI. METHODS: This was a prospective randomized controlled
      single-blind trial conducted from 2006 to 2010 at the University Hospital of
      Basel. Participants were 401 critically ill patients requiring emergent RSI.
      Patients were randomized to receive 1 mg/kg succinylcholine or 0.6 mg/kg
      rocuronium for neuromuscular blockade. The primary outcome was the incidence of
      oxygen desaturations defined as a decrease in oxygen saturation >= 5%, assessed
      by continuous pulse oxymetry, at any time between the start of the induction
      sequence and two minutes after the completion of the intubation. A severe oxygen
      desaturation was defined as a decrease in oxygen saturation >= 5% leading to a
      saturation value of <= 80%. RESULTS: There was no difference between
      succinylcholine and rocuronium regarding oxygen desaturations (succinylcholine
      73/196; rocuronium 66/195; P = 0.67); severe oxygen desaturations
      (succinylcholine 20/196; rocuronium 20/195; P = 1.0); and extent of oxygen
      desaturations (succinylcholine -14 +/- 12%; rocuronium -16 +/- 13%; P = 0.77).
      The duration of the intubation sequence was shorter after succinycholine than
      after rocuronium (81 +/- 38 sec versus 95 +/- 48 sec; P = 0.002). Intubation
      conditions (succinylcholine 8.3 +/- 0.8; rocuronium 8.2 +/- 0.9; P = 0.7) and
      failed first intubation attempts (succinylcholine 32/200; rocuronium 36/201; P =
      1.0) did not differ between the groups. CONCLUSIONS: In critically ill patients
      undergoing emergent RSI, incidence and severity of oxygen desaturations, the
      quality of intubation conditions, and incidence of failed intubation attempts did
      not differ between succinylcholine and rocuronium. TRIAL REGISTRATION:
      ClinicalTrials.gov, number NCT00355368.

PMID- 21846381
TI  - Obesity and craniopharyngioma.
AB  - An epidemic of pediatric obesity has occurred across the world in recent years.
      There are subgroups within the population at high-risk of becoming obese and
      especially of having experience of precocious cardiovascular and metabolic co
      morbidities of obesity. One of these subgroups comprises patients treated for
      childhood cancers and namely survivors of craniopharyngioma. The high incidence
      of obesity in this group makes these patients an important disease model to
      better understand the metabolic disturbances and the mechanisms of weight gain
      among cancer survivors. The hypothalamic-pituitary axis damage secondary to
      cancer therapies or to primary tumor location affect long-term outcomes.
      Nevertheless, the aetiology of obesity in craniopharyngioma is not yet fully
      understood. The present review has the aim of summarizing the published data and
      examining the most accepted mechanisms and main predisposing factors related to
      weight gain in this particular population.

PMID- 21846382
TI  - Polycation stabilization of graphene suspensions.
AB  - Graphene is a leading contender for the next-generation electronic devices. We
      report a method to produce graphene membranes in the solution phase using
      polymeric imidazolium salts as a transferring medium. Graphene membranes were
      reduced from graphene oxides by hydrazine in the presence of the polyelectrolyte
      which is found to be a stable and homogeneous dispersion for the resulting
      graphene in the aqueous solution. A simple device with gold contacts on both
      sides was fabricated in order to observe the electronic properties.

PMID- 21846383
TI  - VACTERL/VATER Association.
AB  - VACTERL/VATER association is typically defined by the presence of at least three
      of the following congenital malformations: vertebral defects, anal atresia,
      cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb
      abnormalities. In addition to these core component features, patients may also
      have other congenital anomalies. Although diagnostic criteria vary, the incidence
      is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The
      condition is ascertained clinically by the presence of the above-mentioned
      malformations; importantly, there should be no clinical or laboratory-based
      evidence for the presence of one of the many similar conditions, as the
      differential diagnosis is relatively large. This differential diagnosis includes
      (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino
      syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns
      syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB
      syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with
      hydrocephalus. Though there are hints regarding causation, the aetiology has been
      identified only in a small fraction of patients to date, likely due to factors
      such as a high degree of clinical and causal heterogeneity, the largely sporadic
      nature of the disorder, and the presence of many similar conditions. New genetic
      research methods offer promise that the causes of VACTERL association will be
      better defined in the relatively near future. Antenatal diagnosis can be
      challenging, as certain component features can be difficult to ascertain prior to
      birth. The management of patients with VACTERL/VATER association typically
      centers around surgical correction of the specific congenital anomalies
      (typically anal atresia, certain types of cardiac malformations, and/or tracheo
      esophageal fistula) in the immediate postnatal period, followed by long-term
      medical management of sequelae of the congenital malformations. If optimal
      surgical correction is achievable, the prognosis can be relatively positive,
      though some patients will continue to be affected by their congenital
      malformations throughout life. Importantly, patients with VACTERL association do
      not tend to have neurocognitive impairment.

PMID- 21846385
TI  - Clinical significance of visceral fat reduction through health education in
      preventing atherosclerotic cardiovascular disease - Lesson from the Amagasaki
      Visceral Fat Study: A Japanese perspective.
AB  - The metabolic syndrome has received worldwide recognition and is useful clinical
      aid in early-preventing atherosclerosis. Visceral adiposity is the main component
      of the metabolic syndrome in Japan, based on ethnic and racial difference in the
      pattern of adiposity. In the Amagasaki Visceral Fat Study, subjects had undergone
      annual health check-ups and then received health education by medical personnel.
      Visceral fat reduction improved hypoadiponectinemia and the number of obesity
      related cardiovascular risk factors, and effectively prevented cardiovascular
      events. The health education that includes voluntary lifestyle modification aimed
      at reducing visceral fat could be useful in preventing cardiovascular events in
      the metabolic syndrome.

PMID- 21846384
TI  - Increased neuroinflammatory and arachidonic acid cascade markers, and reduced
      synaptic proteins, in brain of HIV-1 transgenic rats.
AB  - BACKGROUND: Cognitive impairment has been reported in human immune deficiency
      virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats.
      This impairment has been linked to neuroinflammation, disturbed brain arachidonic
      acid (AA) metabolism, and synapto-dendritic injury. We recently reported
      upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We
      hypothesized that these HIV-1 Tg rats also would show upregulated brain
      inflammatory and AA cascade markers and a deficit of synaptic proteins. METHODS:
      We measured protein and mRNA levels of markers of neuroinflammation and the AA
      cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7
      to 9-month-old HIV-1 Tg and control rats. RESULTS: Compared with control brain,
      HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1
      viral proteins, and significantly higher protein and mRNA levels of (1) the
      inflammatory cytokines interleukin-1beta and tumor necrosis factor alpha, (2) the
      activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA
      selective Ca2+-dependent cytosolic phospholipase A2 (cPLA2)-IVA, secretory sPLA2
      IIA, cyclooxygenase (COX)-2, membrane prostaglandin E2 synthase, 5-lipoxygenase
      (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF
      kappaBp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell
      injury, including significantly decreased levels of brain-derived neurotrophic
      factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines.
      Expression of Ca2+-independent iPLA2-VIA and COX-1 was unchanged. CONCLUSIONS:
      HIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism,
      with a deficit in several synaptic proteins. These changes are associated with
      viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may
      be a useful model for understanding progression and treatment of cognitive
      impairment in HIV-1 patients.

PMID- 21846386
TI  - Association between Body Mass Index and depression: the "fat and jolly"
      hypothesis for adolescents girls.
AB  - BACKGROUND: Results concerning the association between Body Mass Index (BMI) and
      depression in adolescence are conflicting, some describing a linear association
      (increase in BMI with level of depression), some a U-shaped association (both
      underweight and obesity are associated with high levels of depression), and they
      mostly concern small samples. The purpose of this study was to describe the
      association between BMI and depression in a large representative sample of French
      adolescents. METHODS: The association between BMI and depression, measured on the
      Adolescent Depression Rating Scale (ADRS), was tested in a French national
      representative sample of 39542 adolescents aged 17. Self-report data is derived
      from the 2008 ESCAPAD study, an epidemiological study based on a questionnaire
      focused on health and drug consumption. We used spline function analysis to
      describe the association between BMI and depression. RESULTS: The association
      between BMI and depression is significant (p < 0.001) and non-linear for both
      genders, with no effect of parental working and marital status. For boys, there
      is U-shaped association. For girls the shape of the association is complex and
      shows inverted convexity for high levels of BMI. The spline shows higher scores
      for depression among overweight girls than among obese girls. CONCLUSION: There
      is evidence for a gender difference in the association between BMI and depression
      in adolescents, supporting the need to study boys and girls separately.
      Overweight adolescent girls are more likely to be depressed than obese adolescent
      girls, giving support for "fat and jolly" hypothesis not only among older women
      but also among adolescent girls.

PMID- 21846387
TI  - Ligand substitution reactions of a phenolic quinolyl hydrazone; oxidovanadium
      (IV) complexes.
AB  - BACKGROUND: Quinoline ring has therapeutic and biological activities. Quinolyl
      hydrazones constitute a class of excellent chelating agents. Recently, the
      physiological and biological activities of quinolyl hydrazones arise from their
      tendency to form metal chelates with transition metal ions. In this context, we
      have aimed to study the competency effect of a phenolic quinolyl hydrazone (H2L;
      primary ligand) with some auxiliary ligands (Tmen, Phen or Oxine; secondary
      ligands) towards oxidovanadium (IV) ions. RESULTS: Mono- and binuclear
      oxidovanadium (IV) - complexes were obtained from the reaction of a phenolic
      quinolyl hydrazone with oxidovanadium (IV)- ion in absence and presence of
      N,N,N',N'- tetramethylethylenediamine (Tmen), 1,10-phenanthroline (Phen) or 8
      hydroxyquinoline (Oxine). The phenolic quinolyl hydrazone ligand behaves as
      monobasic bidentate (NO- donor with O- bridging). All the obtained complexes have
      the preferable octahedral geometry except the oxinato complex (2) which has a
      square pyramid geometry with no axial interaction; the only homoleptic complex in
      this study. CONCLUSION: The ligand exchange (substitution/replacement) reactions
      reflect the strong competency power of the auxiliary aromatic ligands
      (Phen/Oxine) compared to the phenolic quinolyl hydrazone (H2L) towards
      oxidovanadium (IV) ion; (complexes 2 and 3). By contrast, in case of the more
      flexible aliphatic competitor (Tmen), an adduct was obtained (4). The obtained
      complexes reflect the strength of the ligand field towards the oxidovanadium (IV)
      ion; Oxine or Phen >> phenolic hydrazone (H2L) > Tmen.

PMID- 21846388
TI  - Sequencing of bovine herpesvirus 4 v.test strain reveals important genome
      features.
AB  - BACKGROUND: Bovine herpesvirus 4 (BoHV-4) is a useful model for the human
      pathogenic gammaherpesviruses Epstein-Barr virus and Kaposi's Sarcoma-associated
      Herpesvirus. Although genome manipulations of this virus have been greatly
      facilitated by the cloning of the BoHV-4 V.test strain as a Bacterial Artificial
      Chromosome (BAC), the lack of a complete genome sequence for this strain limits
      its experimental use. METHODS: In this study, we have determined the complete
      sequence of BoHV-4 V.test strain by a pyrosequencing approach. RESULTS: The long
      unique coding region (LUR) consists of 108,241 bp encoding at least 79 open
      reading frames and is flanked by several polyrepetitive DNA units (prDNA). As
      previously suggested, we showed that the prDNA unit located at the left prDNA-LUR
      junction (prDNA-G) differs from the other prDNA units (prDNA-inner). Namely, the
      prDNA-G unit lacks the conserved pac-2 cleavage and packaging signal in its right
      terminal region. Based on the mechanisms of cleavage and packaging of herpesvirus
      genomes, this feature implies that only genomes bearing left and right end prDNA
      units are encapsulated into virions. CONCLUSIONS: In this study, we have
      determined the complete genome sequence of the BAC-cloned BoHV-4 V.test strain
      and identified genome organization features that could be important in other
      herpesviruses.

PMID- 21846389
TI  - Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and
      susceptibility to anti-tuberculosis drugs.
AB  - BACKGROUND: Sudan is a large country with a diverse population and history of
      civil conflict. Poverty levels are high with a gross national income per capita
      of less than two thousand dollars. The country has a high burden of tuberculosis
      (TB) with an estimated 50,000 incident cases during 2009, when the estimated
      prevalence was 209 cases per 100,000 of the population. Few studies have been
      undertaken on TB in Sudan and the prevalence of drug resistant disease is not
      known. METHODS: In this study Mycobacterium tuberculosis isolates from 235
      patients attending three treatment centers in Sudan were screened for
      susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the
      proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by
      spoligotyping. Demographic details of patients were recorded using a structured
      questionnaire. Statistical analyses were conducted to examine the associations
      between drug resistance with risk ratios computed for a set of risk factors
      (gender, age, case status--new or relapse, geographic origin of the patient,
      spoligotype, number of people per room, marital status and type of housing).
      RESULTS: Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least
      rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95%
      CI: 14,34) of previously treated patients. Drug resistance was associated with
      previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for
      resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB.
      Resistance was also associated with the geographic region of origin of the
      patient, being most frequently observed in patients from the Northern region and
      least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: <
      0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR
      TB. The major genotype observed was of the Central Asia spoligotype family
      (CAS1_Delhi), representing 49% of the 232 isolates examined. CONCLUSIONS: We
      conclude that emergence of drug resistant tuberculosis has the potential to be a
      serious public health problem in Sudan and that strengthened tuberculosis control
      and improved monitoring of therapy is needed. Further surveillance is required to
      fully ascertain the extent of the problem.

PMID- 21846390
TI  - Reverse shoulder arthroplasty leads to significant biomechanical changes in the
      remaining rotator cuff.
AB  - OBJECTIVE: After reverse shoulder arthroplasty (RSA) external and internal
      rotation will often remain restricted. A postoperative alteration of the
      biomechanics in the remaining cuff is discussed as a contributing factor to these
      functional deficits. METHODS: In this study, muscle moment arms as well as origin
      to-insertion distance (OID) were calculated using three-dimensional models of the
      shoulder derived from CT scans of seven cadaveric specimens. RESULTS: Moment arms
      for humeral rotation are significantly smaller for the cranial segments of SSC
      and all segments of TMIN in abduction angles of 30 degrees and above (p <= 0.05).
      Abduction moment arms were significantly decreased for all segments (p <= 0.002).
      OID was significantly smaller for all muscles at the 15 degree position (p <=
      0.005), apart from the cranial SSC segment. CONCLUSIONS: Reduced rotational
      moment arms in conjunction with the decrease of OID may be a possible explanation
      for the clinically observed impaired external and internal rotation.

PMID- 21846391
TI  - Psychometric properties and longitudinal validation of the self-reporting
      questionnaire (SRQ-20) in a Rwandan community setting: a validation study.
AB  - BACKGROUND: This study took place to enable the measurement of the effects on
      mental health of a psychosocial intervention in Rwanda. It aimed to establish the
      capacities of the Self-Reporting Questionnaire (SRQ-20) to screen for mental
      disorder and to assess symptom change over time in a Rwandan community setting.
      METHODS: The SRQ-20 was translated into Kinyarwanda in a process of forward and
      back-translation. SRQ-20 data were collected in a Rwandan setting on 418
      respondents; a random subsample of 230 respondents was assessed a second time
      with a three month time interval. Internal reliability was tested using
      Cronbach's alpha. The optimal cut-off point was determined by calculating
      Receiver Operating Curves, using semi-structured clinical interviews as standard
      in a random subsample of 99 respondents. Subsequently, predictive value,
      likelihood ratio, and interrater agreement were calculated. The factor structure
      of the SRQ-20 was determined through exploratory factor analysis. Factorial
      invariance over time was tested in a multigroup confirmatory factor analysis.
      RESULTS: The reliability of the SRQ-20 in women (alpha = 0.85) and men (alpha =
      0.81) could be considered good. The instrument performed moderately well in
      detecting common mental disorders, with an area under the curve (AUC) of 0.76 for
      women and 0.74 for men. Cut-off scores were different for women (10) and men (8).
      Factor analysis yielded five factors, explaining 38% of the total variance. The
      factor structure proved to be time invariant. CONCLUSIONS: The SRQ-20 can be used
      as a screener to detect mental disorder in a Rwandan community setting, but cut
      off scores need to be adjusted for women and men separately. The instrument also
      shows longitudinal factorial invariance, which is an important prerequisite for
      assessing changes in symptom severity. This is a significant finding as in non
      western post-conflict settings the relevance of diagnostic categories is
      questionable. The use of the SRQ-20 can be considered an alternative option for
      measuring the effect of a psychosocial intervention on mental health. TRIAL
      REGISTRATION: Nederlands Trial Register NTR1120.

PMID- 21846392
TI  - Characterization of two common 5' polymorphisms in PEX1 and correlation to
      survival in PEX1 peroxisome biogenesis disorder patients.
AB  - BACKGROUND: Mutations in PEX1 are the most common primary cause of Zellweger
      syndrome. In addition to exonic mutations, deletions and splice site mutations
      two 5' polymorphisms at c.-137 and c.-53 with a potential influence on PEX1
      protein levels have been described in the 5' untranslated region (UTR) of the
      PEX1 gene. METHODS: We used RACE and in silico promoter prediction analysis to
      study the 5' UTR of PEX1. We determined the distribution of PEX1 5' polymorphisms
      in a cohort of 30 Zellweger syndrome patients by standard DNA sequencing. 5'
      polymorphisms were analysed in relation to the two most common mutations in PEX1
      and were incorporated into a novel genotype-phenotype analysis by correlation of
      three classes of PEX1 mutations with patient survival. RESULTS: We provide
      evidence that the polymorphism 137 bp upstream of the ATG codon is not part of
      the UTR, rendering it a promoter polymorphism. We show that the first, but not
      the second most common PEX1 mutation arose independently of a specific upstream
      polymorphic constellation. By genotype-phenotype analysis we identified patients
      with identical exonic mutation and identical 5' polymorphisms, but strongly
      differing survival. CONCLUSIONS: Our study suggests that two different types of
      PEX1 5' polymorphisms have to be distinguished: a 5' UTR polymorphism at position
      c.-53 and a promoter polymorphism 137 bp upstream of the PEX1 start codon. Our
      results indicate that the exonic PEX1 mutation correlates with patient survival,
      but the two 5' polymorphisms analysed in this study do not have to be considered
      for diagnostic and/or prognostic purposes.

PMID- 21846395
TI  - Functional neural correlates of reduced physiological falls risk.
AB  - BACKGROUND: It is currently unclear whether the function of brain regions
      associated with executive cognitive processing are independently associated with
      reduced physiological falls risk. If these are related, it would suggest that the
      development of interventions targeted at improving executive neurocognitive
      function would be an effective new approach for reducing physiological falls risk
      in seniors. METHODS: We performed a secondary analysis of 73 community-dwelling
      senior women aged 65 to 75 years old who participated in a 12-month randomized
      controlled trial of resistance training. Functional MRI data were acquired while
      participants performed a modified Eriksen Flanker Task - a task of selective
      attention and conflict resolution. Brain volumes were obtained using MRI. Falls
      risk was assessed using the Physiological Profile Assessment (PPA). RESULTS:
      After accounting for baseline age, experimental group, baseline PPA score, and
      total baseline white matter brain volume, baseline activation in the left frontal
      orbital cortex extending towards the insula was negatively associated with
      reduced physiological falls risk over the 12-month period. In contrast, baseline
      activation in the paracingulate gyrus extending towards the anterior cingulate
      gyrus was positively associated with reduced physiological falls risk.
      CONCLUSIONS: Baseline activation levels of brain regions underlying response
      inhibition and selective attention were independently associated with reduced
      physiological falls risk. This suggests that falls prevention strategies may be
      facilitated by incorporating intervention components - such as aerobic exercise -
      that are specifically designed to induce neurocognitive plasticity. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT00426881.

PMID- 21846396
TI  - Evolution of response dynamics underlying bacterial chemotaxis.
AB  - BACKGROUND: The ability to predict the function and structure of complex
      molecular mechanisms underlying cellular behaviour is one of the main aims of
      systems biology. To achieve it, we need to understand the evolutionary routes
      leading to a specific response dynamics that can underlie a given function and
      how biophysical and environmental factors affect which route is taken. Here, we
      apply such an evolutionary approach to the bacterial chemotaxis pathway, which is
      documented to display considerable complexity and diversity. RESULTS: We
      construct evolutionarily accessible response dynamics starting from a linear
      response to absolute levels of attractant, to those observed in current-day
      Escherichia coli. We explicitly consider bacterial movement as a two-state
      process composed of non-instantaneous tumbling and swimming modes. We find that a
      linear response to attractant results in significant chemotaxis when sensitivity
      to attractant is low and when time spent tumbling is large. More importantly,
      such linear response is optimal in a regime where signalling has low sensitivity.
      As sensitivity increases, an adaptive response as seen in Escherichia coli
      becomes optimal and leads to 'perfect' chemotaxis with a low tumbling time. We
      find that as tumbling time decreases and sensitivity increases, there exist a
      parameter regime where the chemotaxis performance of the linear and adaptive
      responses overlap, suggesting that evolution of chemotaxis responses might
      provide an example for the principle of functional change in structural
      continuity. CONCLUSIONS: Our findings explain several results from diverse
      bacteria and lead to testable predictions regarding chemotaxis responses evolved
      in bacteria living under different biophysical constraints and with specific
      motility machinery. Further, they shed light on the potential evolutionary paths
      for the evolution of complex behaviours from simpler ones in incremental fashion.

PMID- 21846397
TI  - Murine mammary tumor cells with a claudin-low genotype.
AB  - BACKGROUND: Molecular classification of human breast cancers has identified at
      least 5 distinct tumor subtypes; luminal A, luminal B, Her2-enriched, basal-like
      and claudin-low. The claudin-low subtype was identified in 2007 and is
      characterized by low expression of luminal differentiation markers and claudins
      3, 4 and 7 and high levels of mesenchymal markers. Claudin-low tumors have a
      reported prevalence of 7-14% and these tumors have a poor prognosis. RESULTS: In
      this study we report the characterization of several cell lines established from
      mammary tumors that develop in MTB-IGFIR transgenic mice. Two lines, RM11A and
      RJ348 present with histological features and gene expression patterns that
      resemble claudin-low breast tumors. Specifically, RM11A and RJ348 cells express
      high levels of the mesenchymal genes Zeb1, Zeb2, Twist1 and Twist2 and very low
      levels of E-cadherin and claudins 3, 4 and 7. The RM11A and RJ348 cells are also
      highly tumorigenic when re-introduced into the mammary fat pad of mice.
      CONCLUSIONS: Mammary tumor cells established from MTB-IGFIR transgenic mice can
      be used as in vitro and in vivo model systems to further our understanding of the
      poorly characterized, claudin-low, breast cancer subtype.

PMID- 21846398
TI  - Retroperitoneoscopic radical nephrectomy with a small incision for renal cell
      carcinoma: comparison with the conventional method.
AB  - PURPOSE: When retroperitoneoscopic radical nephrectomy for renal cell carcinoma
      was introduced into our institution, we performed a combined small skin incision
      method. In this method, a small incision was made to approach the retroperitoneal
      space prior to setting trockers and thereafter a LAPDISC was placed in the
      incision to start the retroperitoneoscopic procedure. In this study, we compared
      the outcomes between the combined small skin incision method ("A method"
      hereinafter) and the conventional method ("B method" hereinafter). MATERIAL AND
      METHODS: Among the cases of T1N0M0 suspicious renal cell carcinoma treated at
      Yokohama City University between May 2003 and June 2009, the A method was
      performed in 51 cases and the B method was performed in 33 cases. The factors in
      the outcomes compared between the A and B methods were the duration of procedure,
      volume of bleeding, volume of transfusion, weight of the specimen, incidence of
      peritoneal injury, rate of conversion to open surgery, and perioperative
      complications. RESULTS: The duration of the procedure was 214.4 +/- 46.9 minutes
      in the A method group and 208.1 +/- 36.4 minutes in the B method group (p =
      0.518). The volume of bleeding and the weight of the specimen were 105.5 +/-
      283.2 ml and 335.1 +/- 137.4 g in the A method group and 44.8 +/- 116 ml (p =
      0.247) and 309.2 +/- 126 g (p = 0.385) in the B method group. There was no
      significant difference in all factors analyzed. CONCLUSION: The A method would be
      highly possible to produce stable results, even during the introduction period
      when the staff and the institution are still unfamiliar with the
      retroperitoneoscopic surgery.

PMID- 21846399
TI  - Cut off values of waist circumference and associated cardiovascular risk in
      Egyptians.
AB  - BACKGROUND: Recent guidelines stressed the need to adopt different values of
      waist circumference (WC) measurements to define abdominal obesity in different
      ethnic groups. The aim of this study is to identify WC cutoff points in
      normotensive and hypertensive subjects which are diagnostic of abdominal obesity
      in a Middle Eastern population and the prevalence of abdominal obesity in a
      nationwide sample. METHODS: Data were collected during phase-2 of the Egyptians
      National Hypertension Project survey. Blood pressure, anthropometric measurements
      and laboratory studies were performed according to a standardized protocol by
      trained personnel. To derive the cutoff points for WC, we applied the factor
      analysis on CV risk factors: diabetes mellitus, decrease in HDL-C and increase in
      LDL-C, triglycerides and left ventricular mass index by echocardiography.
      RESULTS: The sample included 2313 individuals above the age of 25 years. WC
      values (mean +/- SD) were 88 +/- 14 cm and 95 +/- 14 cm for normotensive (NT) and
      hypertensive (HT) men respectively, and 89.6 +/- 14.7 cm and 95.7 +/- 15.9 cm for
      NT and HT women respectively. Applying factor analysis, the weighted average
      cutoff points were 93.5 cm for both NT and HT men and 91.5 and 92.5 cm for NT and
      HT women respectively. Based on these thresholds, the prevalence of abdominal
      obesity was 48% in men and 51.5% in women. CONCLUSION: This is the first report
      of specific abdominal obesity cutoff points in a Middle Eastern country. The
      cutoff points were different from the Europid standards. There is a high
      prevalence rate of abdominal obesity among Egyptians which is associated with
      increased prevalence of cardiometabolic risk factors.

PMID- 21846400
TI  - Long-term declines in ADLs, IADLs, and mobility among older Medicare
      beneficiaries.
AB  - BACKGROUND: Most prior studies have focused on short-term (<= 2 years) functional
      declines. But those studies cannot address aging effects inasmuch as all
      participants have aged the same amount. Therefore, the authors studied the extent
      of long-term functional decline in older Medicare beneficiaries who were followed
      for varying time lengths, and the authors also identified the risk factors
      associated with those declines. METHODS: The analytic sample included 5,871 self-
      or proxy-respondents who had complete baseline and follow-up survey data that
      could be linked to their Medicare claims for 1993-2007. Functional status was
      assessed using activities of daily living (ADLs), instrumental ADLs (IADLs), and
      mobility limitations, with declines defined as the development of two of more new
      difficulties. Multiple logistic regression analysis was used to focus on the
      associations involving respondent status, health lifestyle, continuity of care,
      managed care status, health shocks, and terminal drop. RESULTS: The average
      amount of time between the first and final interviews was 8.0 years. Declines
      were observed for 36.6% on ADL abilities, 32.3% on IADL abilities, and 30.9% on
      mobility abilities. Functional decline was more likely to occur when proxy
      reports were used, and the effects of baseline function on decline were reduced
      when proxy-reports were used. Engaging in vigorous physical activity consistently
      and substantially protected against functional decline, whereas obesity,
      cigarette smoking, and alcohol consumption were only associated with mobility
      declines. Post-baseline hospitalizations were the most robust predictors of
      functional decline, exhibiting a dose-response effect such that the greater the
      average annual number of hospital episodes, the greater the likelihood of
      functional status decline. Participants whose final interview preceded their
      death by one year or less had substantially greater odds of functional status
      decline. CONCLUSIONS: Both the additive and interactive (with functional status)
      effects of respondent status should be taken into consideration whenever proxy
      reports are used. Encouraging exercise could broadly reduce the risk of
      functional decline across all three outcomes, although interventions encouraging
      weight reduction and smoking cessation would only affect mobility declines.
      Reducing hospitalization and re-hospitalization rates could also broadly reduce
      the risk of functional decline across all three outcomes.

PMID- 21846401
TI  - Comparative effectiveness of asthma interventions within a practice based
      research network.
AB  - BACKGROUND: Asthma is a chronic lung disease that affects more than 23 million
      people in the United States, including 7 million children. Asthma is a difficult
      to manage chronic condition associated with disparities in health outcomes, poor
      medical compliance, and high healthcare costs. The research network coordinating
      this project includes hospitals, urgent care centers, and outpatient clinics
      within Carolinas Healthcare System that share a common electronic medical record
      and billing system allowing for rapid collection of clinical and demographic
      data. This study investigates the impact of three interventions on clinical
      outcomes for patients with asthma. Interventions are: an integrated approach to
      care that incorporates asthma management based on the chronic care model; a
      shared decision making intervention for asthma patients in underserved or
      disadvantaged populations; and a school based care approach that examines the
      efficacy of school-based programs to impact asthma outcomes including
      effectiveness of linkages between schools and the healthcare providers.
      METHODS/DESIGN: This study will include 95 Practices, 171 schools, and over
      30,000 asthmatic patients. Five groups (A-E) will be evaluated to determine the
      effectiveness of three interventions. Group A is the usual care control group
      without electronic medical record (EMR). Group B practices are a second control
      group that has an EMR with decision support, asthma action plans, and population
      reports at baseline. A time delay design during year one converts practices in
      Group B to group C after receiving the integrated approach to care intervention.
      Four practices within Group C will receive the shared decision making
      intervention (and become group D). Group E will receive a school based care
      intervention through case management within the schools. A centralized database
      will be created with the goal of facilitating comparative effectiveness research
      on asthma outcomes specifically for this study. Patient and community level
      analysis will include results from patient surveys, focus groups, and asthma
      patient density mapping. Community variables such as income and housing density
      will be mapped for comparison. Outcomes to be measured are reduced
      hospitalizations and emergency department visits; improved adherence to
      medication; improved quality of life; reduced school absenteeism; improved self
      efficacy and improved school performance. DISCUSSION: Identifying new mechanisms
      that improve the delivery of asthma care is an important step towards advancing
      patient outcomes, avoiding preventable Emergency Department visits and
      hospitalizations, while simultaneously reducing overall healthcare costs.

PMID- 21846402
TI  - The effects of nationality differences and work stressors on work adjustment for
      foreign nurse aides.
AB  - BACKGROUND: The main purpose of this study was to discuss the nationality
      differences of foreign nurse aides and the effect of work stressors influencing
      work adjustment. And of helping them adapt to Taiwanese society, we summarized
      the difficulties that foreign nurse aides face in Taiwan. METHODS: The subjects
      included 80 foreign nurse aides from the Philippines, Indonesia, and Vietnam who
      worked in long-term care facilities in Tao Yuan County. We recruited volunteers
      at the participating facilities to complete the anonymous questionnaires. The
      return rate of the questionnaire was 88.75%. The validated instruments of
      Hershenson's (1981) and Schaefer and Moos (1993) were adopted to measure work
      stressors and work adjustment, respectively. A forward-backward translation
      process was used in this study. RESULTS: Indonesian foreign nurse aides respect
      their work, and are better workers than Vietnamese and Filipino nurse aids in
      many respects, which shows how the nationality of the foreign nurse aides might
      affect work adjustment. The stress created from patient care tasks influenced the
      foreign nurse aides' personal relationships at work and also affected their
      attitude when they performed their tasks. In addition, pressure from their
      supervisors might have affected their work skills, work habits, personal
      relationships, self-concepts or work attitudes. Moreover, a heavy workload and
      improper scheduling might have affected the personal relationships and work
      attitudes of the foreign nurse aides. It was found that work stressors had a
      significant correlation with work adjustment. CONCLUSIONS: The results of the
      present study indicate that training programs are important factors for work
      adjustment among foreign nurse aides. Furthermore, celebration and leisure
      activities could be provided to release them from work stressors. More effort
      should be put into improving the working environment, namely providing a more
      supportive and enriching atmosphere. Based on these findings, we have a better
      understanding of how to assist foreign nurse aides in the future.

PMID- 21846403
TI  - Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine
      aminotransferase gene expression and enzymatic activity in the rat liver.
AB  - BACKGROUND: Traditional assessment of drug-induced hepatotoxicity includes
      morphological examination of the liver and evaluation of liver enzyme activity in
      serum. The objective of the study was to determine the origin of drug-related
      elevation in serum alanine aminotransferase (ALT) activity in the absence of
      morphologic changes in the liver by utilizing molecular and immunohistochemical
      techniques. METHODS: Sixteen female Sprague-Dawley rats were divided into 2
      groups (control and treated, n = 4 per group) and treated rats were dosed orally
      twice daily (400 mg/kg/day) for 7 days with a VEGFR-2 compound (AG28262), which
      in a previous study caused ALT elevation without morphological changes. Serum of
      both treated and control animals were evaluated on day 3 of treatment and at day
      8. Three separate liver lobes (caudate, right medial, and left lateral) were
      examined for determination of ALT tissue activity, ALT gene expression and
      morphological changes. RESULTS: ALT activity was significantly (p < 0.01)
      elevated on day 3 and further increased on day 8. Histologic changes or increase
      in TUNEL and caspase3 positive cells were not observed in the liver lobes
      examined. ALT gene expression in the caudate lobe was significantly up-regulated
      by 63%. ALT expression in the left lateral lobe was not significantly affected.
      Statistically significant increased liver ALT enzymatic activity occurred in the
      caudate (96%) and right medial (41%) lobes but not in the left lateral lobe.
      CONCLUSIONS: AG28262, a VEFG-r2 inhibitor, causes an increase in serum ALT, due
      in part to both gene up-regulation. Differences between liver lobes may be
      attributable to differential distribution of blood from portal circulation.
      Incorporation of molecular data, such as gene and protein expression, and
      sampling multiple liver lobes may shed mechanistic insight to the evaluation of
      hepatotoxicity.

PMID- 21846404
TI  - Prediction of conformational B-cell epitopes from 3D structures by random forests
      with a distance-based feature.
AB  - BACKGROUND: Antigen-antibody interactions are key events in immune system, which
      provide important clues to the immune processes and responses. In Antigen
      antibody interactions, the specific sites on the antigens that are directly bound
      by the B-cell produced antibodies are well known as B-cell epitopes. The
      identification of epitopes is a hot topic in bioinformatics because of their
      potential use in the epitope-based drug design. Although most B-cell epitopes are
      discontinuous (or conformational), insufficient effort has been put into the
      conformational epitope prediction, and the performance of existing methods is far
      from satisfaction. RESULTS: In order to develop the high-accuracy model, we focus
      on some possible aspects concerning the prediction performance, including the
      impact of interior residues, different contributions of adjacent residues, and
      the imbalanced data which contain much more non-epitope residues than epitope
      residues. In order to address above issues, we take following strategies.
      Firstly, a concept of 'thick surface patch' instead of 'surface patch' is
      introduced to describe the local spatial context of each surface residue, which
      considers the impact of interior residue. The comparison between the thick
      surface patch and the surface patch shows that interior residues contribute to
      the recognition of epitopes. Secondly, statistical significance of the distance
      distribution difference between non-epitope patches and epitope patches is
      observed, thus an adjacent residue distance feature is presented, which reflects
      the unequal contributions of adjacent residues to the location of binding sites.
      Thirdly, a bootstrapping and voting procedure is adopted to deal with the
      imbalanced dataset. Based on the above ideas, we propose a new method to identify
      the B-cell conformational epitopes from 3D structures by combining conventional
      features and the proposed feature, and the random forest (RF) algorithm is used
      as the classification engine. The experiments show that our method can predict
      conformational B-cell epitopes with high accuracy. Evaluated by leave-one-out
      cross validation (LOOCV), our method achieves the mean AUC value of 0.633 for the
      benchmark bound dataset, and the mean AUC value of 0.654 for the benchmark
      unbound dataset. When compared with the state-of-the-art prediction models in the
      independent test, our method demonstrates comparable or better performance.
      CONCLUSIONS: Our method is demonstrated to be effective for the prediction of
      conformational epitopes. Based on the study, we develop a tool to predict the
      conformational epitopes from 3D structures, available at
      http://code.google.com/p/my-project-bpredictor/downloads/list.

PMID- 21846405
TI  - Limb salvage after gas gangrene: a case report and review of the literature.
AB  - Gas gangrene is a necrotic infection of soft tissue associated with high
      mortality, often necessitating amputation in order to control the infection.
      Herein we present a case of gas gangrene of the arm in an intravenous drug user
      with a history of intramuscular injections with normal saline in the shoulder
      used to provoke pain for recovery after drug induced coma. The patient was early
      treated with surgery and antibiotics rendering possible the preservation of the
      limb and some of its function. Additionally, a review of the literature regarding
      case reports of limb salvage after gas gangrene is presented.

PMID- 21846406
TI  - Accuracy of 64-multidetector computed tomography in diagnosis of adnexal tumors.
AB  - BACKGROUND: Adnexal cancers are in fifth place among the tumors with the highest
      mortality in the female population. The aim of the present study was to evaluate
      the accuracy of Multi-detector computed tomography (MDCT) on a 64-multislice CT
      scanner in the detection and differentiation of adnexal masses stages. METHODS:
      During the present prospective study, 95 women with a primary diagnosis of
      ovarian mass in base of clinical examination and ultrasonographic findings
      underwent preoperative evaluation by a 64-slice MDCT with a section thickness of
      0.6 mm, 50% overlap and reconstructed images. Afterward, results of MDCT were
      compared with surgical and histopathological findings, and the sensitivity,
      specificity, positive and negative predictive value and accuracy were determined.
      RESULTS: The mean age of patients was 48.63 +/- 13.93 years. MDCT diagnosed 25
      (26.3%) masses to be benign and 70 (73.7%) to be malignant (sensitivity,
      specificity, positive and negative predictive value and accuracy were 92.8%,
      88.0%, 95.5%, 81.4% and 91.5% respectively). The sensitivity and specificity of
      MDCT in determining local extension was 72.2% and 93.4% respectively. And the
      sensitivity and specificity of MDCT in determining peritoneal seeding and liver
      extension was 81.8% and 93% respectively. Estimated stage was significantly
      agreed with the surgical (Cohen's Kappa (kappa) = 0.891) and histopathological
      findings (kappa = 0.858). CONCLUSION: MDCT is a highly sensitive and specific
      diagnostic method in evaluation of adnexal masses and successfully stage the
      tumor in consistent with surgery and histopathology.

PMID- 21846407
TI  - The time burden of overweight and obesity in primary care.
AB  - BACKGROUND: Overweight and obesity are associated with many conditions treated in
      primary care. Our objectives were: 1) to determine the frequency of weight
      related conditions in a national sample of outpatient visits in the United
      States; 2) to establish the percentage of diagnosis codes and visit codes
      attributable to overweight and obesity; and 3) to estimate time spent to address
      these conditions, including time attributable to overweight and obesity itself.
      METHODS: We analyzed primary care visits from the 2005 and 2006 National
      Ambulatory Medical Care Survey (NAMCS) in the United States. Weight-related
      conditions included diabetes, hypertension, hyperlipidemia, obesity,
      cardiovascular disease, osteoarthritis, and low back pain. We used multivariable
      logistic regression to estimate an odds ratio for each weight-related condition,
      which we then converted to an attributable fraction (AF). The AF represents the
      percentage of diagnosis codes and visit codes attributable to excess weight for
      that condition. We then divided total visit time among all diagnoses and clinical
      items addressed at the primary care visit. Finally, to calculate the time
      attributable to overweight and obesity, we multiplied the AFs by the time spent
      on each weight-related condition. RESULTS: The total number of clinical items
      (diagnoses + medications + tests + counseling) was estimated to be 7.6 per
      patient, of which 2.2 were weight-related. Of a total visit time of 21.77
      minutes, time spent addressing weight-related conditions was 5.65 minutes (30%),
      including 1.75 minutes (8.0%) attributable to overweight and obesity.
      CONCLUSIONS: Approximately 8% of time from primary care visits is attributable to
      overweight and obesity. This estimate is conservative because the NAMCS only
      allows for coding of three diagnoses addressed per visit. Estimates of the time
      burden of overweight and obesity provide data to prioritize weight management for
      prevention and treatment.

PMID- 21846408
TI  - Tight associations between transcription promoter type and epigenetic variation
      in histone positioning and modification.
AB  - BACKGROUND: Transcription promoters are fundamental genomic cis-elements
      controlling gene expression. They can be classified into two types by the degree
      of imprecision of their transcription start sites: peak promoters, which initiate
      transcription from a narrow genomic region; and broad promoters, which initiate
      transcription from a wide-ranging region. Eukaryotic transcription initiation is
      suggested to be associated with the genomic positions and modifications of
      nucleosomes. For instance, it has been recently shown that histone with H3K9
      acetylation (H3K9ac) is more likely to be distributed around broad promoters
      rather than peak promoters; it can thus be inferred that there is an association
      between histone H3K9 and promoter architecture. RESULTS: Here, we performed a
      systematic analysis of transcription promoters and gene expression, as well as of
      epigenetic histone behaviors, including genomic position, stability within the
      chromatin, and several modifications. We found that, in humans, broad promoters,
      but not peak promoters, generally had significant associations with nucleosome
      positioning and modification. Specifically, around broad promoters histones were
      highly distributed and aligned in an orderly fashion. This feature was more
      evident with histones that were methylated or acetylated; moreover, the
      nucleosome positions around the broad promoters were more stable than those
      around the peak ones. More strikingly, the overall expression levels of genes
      associated with broad promoters (but not peak promoters) with modified histones
      were significantly higher than the levels of genes associated with broad
      promoters with unmodified histones. CONCLUSION: These results shed light on how
      epigenetic regulatory networks of histone modifications are associated with
      promoter architecture.

PMID- 21846409
TI  - Improving the efficiency of feed utilization in poultry by selection. 2. Genetic
      parameters of excretion traits and correlations with anatomy of the gastro
      intestinal tract and digestive efficiency.
AB  - BACKGROUND: Poultry production has been widely criticized for its negative
      environmental impact related to the quantity of manure produced and to its
      nitrogen and phosphorus content. In this study, we investigated which traits
      related to excretion could be used to select chickens for lower environmental
      pollution.The genetic parameters of several excretion traits were estimated on
      630 chickens originating from 2 chicken lines divergently selected on apparent
      metabolisable energy corrected for zero nitrogen (AMEn) at constant body weight.
      The quantity of excreta relative to feed consumption (CDUDM), the nitrogen and
      phosphorus excreted, the nitrogen to phosphorus ratio and the water content of
      excreta were measured, and the consequences of such selection on performance and
      gastro-intestinal tract (GIT) characteristics estimated. The genetic correlations
      between excretion, GIT and performance traits were established. RESULTS:
      Heritability estimates were high for CDUDM and the nitrogen excretion rate (0.30
      and 0.29, respectively). The other excretion measurements showed low to moderate
      heritability estimates, ranging from 0.10 for excreta water content to 0.22 for
      the phosphorus excretion rate. Except for the excreta water content, the CDUDM
      was highly correlated with the excretion traits, ranging from -0.64 to -1.00. The
      genetic correlations between AMEn or CDUDM and the GIT characteristics were very
      similar and showed that a decrease in chicken excretion involves an increase in
      weight of the upper part of the GIT, and a decrease in the weight of the small
      intestine. CONCLUSION: In order to limit the environmental impact of chicken
      production, AMEn and CDUDM seem to be more suitable criteria to include in
      selection schemes than feed efficiency traits.

PMID- 21846410
TI  - Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology.
AB  - BACKGROUND: Worldwide, acute leukemia is the most common type of childhood
      cancer. It is particularly common in the Hispanic populations residing in the
      United States, Costa Rica, and Mexico City. The objective of this study was to
      determine the incidence of acute leukemia in children who were diagnosed and
      treated in public hospitals in Mexico City. METHODS: Included in this study were
      those children, under 15 years of age and residents of Mexico City, who were
      diagnosed in 2006 and 2007 with leukemia, as determined by using the
      International Classification of Childhood Cancer. The average annual incidence
      rates (AAIR), and the standardized average annual incidence rates (SAAIR) per
      million children were calculated. We calculated crude, age- and sex-specific
      incidence rates and adjusted for age by the direct method with the world
      population as standard. We determined if there were a correlation between the
      incidence of acute leukemias in the various boroughs of Mexico City and either
      the number of agricultural hectares, the average number of persons per household,
      or the municipal human development index for Mexico (used as a reference of socio
      economic level). RESULTS: Although a total of 610 new cases of leukemia were
      registered during 2006-2007, only 228 fit the criteria for inclusion in this
      study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute
      lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting
      85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic
      leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7%
      (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL
      (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype
      (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per
      million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the
      children (58.8%) were classified as high risk. There was a positive correlation
      between the average number of persons per household and the incidence of the pre
      B immunophenotype (Pearson's r, 0.789; P = 0.02). CONCLUSIONS: The frequency of
      ALL in Mexico City is among the highest in the world, similar to those found for
      Hispanics in the United States and in Costa Rica.

PMID- 21846411
TI  - Comparison of ring artifact removal methods using flat panel detector based CT
      images.
AB  - BACKGROUND: Ring artifacts are the concentric rings superimposed on the
      tomographic images often caused by the defective and insufficient calibrated
      detector elements as well as by the damaged scintillator crystals of the flat
      panel detector. It may be also generated by objects attenuating X-rays very
      differently in different projection direction. Ring artifact reduction techniques
      so far reported in the literature can be broadly classified into two groups. One
      category of the approaches is based on the sinogram processing also known as the
      pre-processing techniques and the other category of techniques perform processing
      on the 2-D reconstructed images, recognized as the post-processing techniques in
      the literature. The strength and weakness of these categories of approaches are
      yet to be explored from a common platform. METHOD: In this paper, a comparative
      study of the two categories of ring artifact reduction techniques basically
      designed for the multi-slice CT instruments is presented from a common platform.
      For comparison, two representative algorithms from each of the two categories are
      selected from the published literature. A very recently reported state-of-the-art
      sinogram domain ring artifact correction method that classifies the ring
      artifacts according to their strength and then corrects the artifacts using class
      adaptive correction schemes is also included in this comparative study. The first
      sinogram domain correction method uses a wavelet based technique to detect the
      corrupted pixels and then using a simple linear interpolation technique estimates
      the responses of the bad pixels. The second sinogram based correction method
      performs all the filtering operations in the transform domain, i.e., in the
      wavelet and Fourier domain. On the other hand, the two post-processing based
      correction techniques actually operate on the polar transform domain of the
      reconstructed CT images. The first method extracts the ring artifact template
      vector using a homogeneity test and then corrects the CT images by subtracting
      the artifact template vector from the uncorrected images. The second post
      processing based correction technique performs median and mean filtering on the
      reconstructed images to produce the corrected images. RESULTS: The performances
      of the comparing algorithms have been tested by using both quantitative and
      perceptual measures. For quantitative analysis, two different numerical
      performance indices are chosen. On the other hand, different types of artifact
      patterns, e.g., single/band ring, artifacts from defective and mis-calibrated
      detector elements, rings in highly structural object and also in hard object,
      rings from different flat-panel detectors are analyzed to perceptually
      investigate the strength and weakness of the five methods. An investigation has
      been also carried out to compare the efficacy of these algorithms in correcting
      the volume images from a cone beam CT with the parameters determined from one
      particular slice. Finally, the capability of each correction technique in
      retaining the image information (e.g., small object at the iso-center) accurately
      in the corrected CT image has been also tested. CONCLUSIONS: The results show
      that the performances of the algorithms are limited and none is fully suitable
      for correcting different types of ring artifacts without introducing processing
      distortion to the image structure. To achieve the diagnostic quality of the
      corrected slices a combination of the two approaches (sinogram- and post
      processing) can be used. Also the comparing methods are not suitable for
      correcting the volume images from a cone beam flat-panel detector based CT.

PMID- 21846412
TI  - Bronchiectasis.
AB  - INTRODUCTION: Bronchiectasis is usually a complication of previous lower
      respiratory infection, and causes chronic cough and copious production of sputum,
      which is often purulent. Bronchiectasis may cause signs of chronic obstructive
      pulmonary disease. It can also be associated with cystic fibrosis and other
      congenital disorders, foreign body inhalation, and other causes of lung damage.
      METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
      following clinical question: What are the effects of treatments in people with
      bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to April 2011 (Clinical
      Evidence reviews are updated periodically; please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE
      evaluation of the quality of evidence for interventions. RESULTS: We found 19
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. CONCLUSIONS: In this systematic review we present information relating
      to the effectiveness and safety of the following interventions: anticholinergic
      therapy, beta(2) agonists, bronchopulmonary hygiene physical therapy,
      corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar
      agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral),
      mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and
      surgery.

PMID- 21846413
TI  - Fungal toenail infections.
AB  - INTRODUCTION: Fungal infections are reported to cause 23% of foot diseases and
      50% of nail conditions in people seen by dermatologists, but are less common in
      the general population, affecting 3% to 5% of people. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of oral treatments for fungal toenail infections?
      What are the effects of topical treatments for fungal toenail infections? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to March 2011 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found 12 systematic reviews, RCTs, or observational studies that met
      our inclusion criteria. We performed a GRADE evaluation of the quality of
      evidence for interventions. CONCLUSIONS: In this systematic review we present
      information relating to the effectiveness and safety of the following
      interventions: amorolfine, butenafine, ciclopirox, fluconazole, griseofulvin,
      itraconazole, ketoconazole, mechanical debridement, terbinafine, and tioconazole.

PMID- 21846414
TI  - Failure of propranolol in the treatment of childhood haemangiomas of the head and
      neck.
AB  - BACKGROUND: Infantile haemangiomas enter a rapid proliferative phase within
      months of birth, before slowly involuting. Those with the potential for
      disfigurement or morbidity require intervention. Propranolol has emerged as an
      effective new treatment modality, with the potential to become the first-line
      treatment of choice. METHODS: Four children with haemangiomas of the head and
      neck were treated with propranolol at a tertiary referral centre. The size of the
      haemangioma and the symptoms resulting from airway compromise were monitored.
      RESULTS: Three of the four children showed a dramatic response to treatment with
      propranolol. However, one child responded initially but was readmitted with
      stridor secondary to new haemangioma proliferation. CONCLUSIONS: We report a
      cautionary case in which a subglottic haemangioma developed contemporaneously
      with propranolol treatment, requiring surgical intervention. This finding
      highlights the need for regular follow up of treatment response, and the need for
      monitoring for treatment side effects.

PMID- 21846415
TI  - Coblation for epistaxis management in patients with hereditary haemorrhagic
      telangiectasia: a multicentre case series.
AB  - OBJECTIVE: To propose radiofrequency coblation as a potential treatment modality
      for mild to moderate epistaxis in patients with hereditary haemorrhagic
      telangiectasia. METHOD: Case reports and review of the world literature
      concerning coblation and other treatment modalities for epistaxis in patients
      with hereditary haemorrhagic telangiectasia. RESULTS: Effective epistaxis control
      was achieved in four out of five cases of hereditary haemorrhagic telangiectasia.
      In the fifth case, we struggled to achieve haemostasis due to disease severity.
      CONCLUSION: Radiofrequency coblation is a novel technique, which was found to be
      a safe, effective, quick and well tolerated treatment option for epistaxis
      management in patients with hereditary haemorrhagic telangiectasia.

PMID- 21846416
TI  - A new era in supraglottitis? An isolated UK case of supraglottitis secondary to
      Neisseria meningitidis.
AB  - OBJECTIVE: We report the first UK case of supraglottitis secondary to Neisseria
      meningitidis. METHOD: Case report with review of the current literature on
      supraglottitis and its aetiology. RESULTS: An 89-year-old woman was referred with
      worsening symptoms of dysphagia, hoarseness and neck discomfort. After
      nasopharyngoscopy and neck X-ray, supraglottitis was diagnosed. Prompt treatment
      comprised nebulised adrenaline, oxygen therapy and intravenous antibiotics.
      Microbiology samples grew N meningitidis, a notifiable disease in the UK. Public
      health officials were informed, and full precautions and prophylactic treatment
      initiated for those at risk. The patient made excellent progress and was
      discharged several days later. DISCUSSION AND CONCLUSION: Supraglottitis occurs
      in <4 per 100 000 population. Following a successful UK childhood immunisation
      programme, most cases occur in adults. Supraglottitis secondary to N meningitidis
      is exceptionally rare, with only seven other reported cases worldwide. Morbidity
      is exceptionally high; over 60 per cent of patients require airway intervention.
      To our knowledge, this is the first reported UK case of supraglottitis secondary
      to N meningitidis. This case highlights the important clinical, diagnostic and
      therapeutic interventions required to prevent complications associated with this
      potentially fatal condition.

PMID- 21846417
TI  - Spectrum of radiological appearances of necrotising external otitis: a pictorial
      review.
AB  - Necrotising external otitis, also known as malignant otitis externa, is an
      aggressive, resorptive osteomyelitis of the temporal bone. Although rare,
      necrotising external otitis is a potentially fatal disease, with complications
      which include temporomandibular joint osteomyelitis, sigmoid sinus thrombosis and
      meningitis. Imaging findings may be subtle, particularly in the early stages. We
      present a broad range of imaging findings which may occur in necrotising external
      otitis cases.

PMID- 21846418
TI  - Cholesteatoma in patients with congenital external auditory canal anomalies:
      retrospective review.
AB  - OBJECTIVE: To review cases of congenital external auditory canal anomaly with
      cholesteatoma, documenting clinical presentation, cholesteatoma site and extent,
      complications, and surgery. METHOD: Retrospective review of all cases of
      congenital canal anomaly with cholesteatoma treated between 1998 and 2009.
      RESULTS: Of 41 cases with canal anomalies, 17 (43.9 per cent) had associated
      cholesteatoma. Medical records were unretrievable for four cases. Of the
      remaining 13 patients (five females and eight males, age range four to 73 years,
      mean 21 years), 10 presented chiefly with recurrent otorrhoea, two with
      postauricular discharge from mastoid abscess, and one with otalgia, postauricular
      tenderness and neck stiffness. Hearing loss was conductive in 10 patients (76.9
      per cent) and sensorineural (severe to profound) in three. No facial nerve palsy
      was documented. Cholesteatoma was seen in all cases on high resolution computed
      tomography, and confirmed intra-operatively. Six patients underwent canalplasty
      with split skin grafting, and seven modified radical mastoidectomy. Six patients
      recovered well, two needed repeated canalplasty for soft tissue restenosis, and
      five needed cautery and split skin grafting for mastoid cavity granulation
      tissue. CONCLUSION: Congenital canal anomaly is uncommon. Canal cholesteatoma
      should be suspected in all cases, and high resolution temporal bone computed
      tomography undertaken in all patients aged four years or more. In patients with
      otorrhoea, the risk of cholesteatoma is greater. Treatment is generally surgery;
      the type depends on the disease extent.

PMID- 21846419
TI  - An arteriovenous malformation within the internal acoustic meatus and
      cerebellopontine angle cistern.
AB  - OBJECTIVES: We report a case of an arteriovenous malformation within the internal
      auditory meatus and cerebellopontine angle, and we discuss its imaging
      appearances and management. CASE REPORT: A 50-year-old man presented with a two
      year history of vertigo. Magnetic resonance imaging and magnetic resonance
      angiography demonstrated a lesion consisting of multiple 'high flow' vessels
      within the left internal auditory meatus and cerebellopontine angle.
      Transarterial embolisation was performed, with obliteration of the arteriovenous
      malformation. CONCLUSION: Arteriovenous malformations of the internal auditory
      meatus and cerebellopontine angle are exceedingly rare. It is important that a
      pre-treatment diagnosis is made, as the management of arteriovenous malformation
      differs from that of other, more common lesions at this site.

PMID- 21846420
TI  - Wegener's granulomatosis mimicking skull base osteomyelitis.
AB  - OBJECTIVE: To report a case of Wegener's granulomatosis mimicking skull base
      osteomyelitis. CASE REPORT: A case of Wegener's granulomatosis is reported in a
      diabetic woman presenting with facial palsy and hearing loss. The clinical course
      of the disease was very similar to that of skull base osteomyelitis, especially
      since the patient was diabetic and the ear swab was positive for pseudomonas. The
      definitive diagnosis was made based on clinical presentation, imaging and serum
      antineutrophil cytoplasmic antibody testing. The patient was started on
      immunosuppressants, and her hearing loss and facial palsy recovered. CONCLUSION:
      Wegener's granulomatosis is a systemic disease with various manifestations. A
      high index of clinical suspicion is required to reach the correct diagnosis. The
      clinician should be alerted to the possibility of Wegener's granulomatosis in the
      presence of: systemic upset out of proportion to the apparent intensity of the
      local lesion; middle-ear disease failing to respond to conventional treatment;
      and a consistently raised erythrocyte sedimentation rate.

PMID- 21846421
TI  - Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive
      changes in 5-HT4 receptor levels.
AB  - Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for
      psychiatric disorder and has been linked to changes in the expression of certain
      5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT
      expression on 5-HT4 receptor levels in both 5-HTT knockout (KO) and
      overexpressing (OE) mice using autoradiography with the selective 5-HT4 receptor
      radioligand, [3H]SB207145. Compared to wild-type (5-HTT+/+) controls, homozygous
      5-HTT KO mice (5-HTT-/-) had reduced 5-HT4 receptor binding site density in all
      brain regions examined (35-65% of 5-HTT+/+). In contrast, the density of 5-HT4
      receptor binding sites was not significantly different between heterozygous 5-HTT
      KO mice (5-HTT-/+) and 5-HTT+/+ mice. The 5-HT synthesis inhibitor p
      chlorophenylalanine (250 mg/kg twice daily for 3 d) abolished the difference in 5
      HT4 binding between 5-HTT-/- and 5-HTT+/+ mice in all brain regions. Compared to
      wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT4 binding
      density across all brain regions, except amygdala (118-164% of WT) and this
      difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20
      mg/kg twice daily, 3 d). Together, these findings suggest that variation in 5-HTT
      expression causes adaptive changes in 5-HT4 receptor levels which are directly
      linked to alterations in 5-HT availability.

PMID- 21846422
TI  - Criminal conviction among offspring with parental history of mental disorder.
AB  - BACKGROUND: Offspring of parents with mental disorder are at risk of a range of
      adverse outcomes. We sought to establish whether such risks extend to offending
      by examining rates of criminal conviction, including conviction for violent and
      sexual offences, among offspring of parents with mental disorder compared to
      offspring without parental disorder. METHOD: From a random sample of the Danish
      population, a cohort aged <=15 years (n=412,117) was followed for the occurrence
      of conviction between January 1981 and December 2006. Incidence rate ratios
      (IRRs) and cumulative incidences for offspring conviction by parental mental
      disorder status were calculated using a Cox regression model. Analyses were
      repeated for conviction for a serious first offence. RESULTS: Offspring with
      history of parental mental disorder had higher rates of conviction than those
      without parental disorder; rates were highest for those with two affected parents
      [IRR 3.39, 95% confidence interval (CI) 3.08-3.73]. The association persisted
      when parental gender, offspring gender and the nature of parental disorder were
      considered. Absolute rates were lower but relative rates higher for female
      offspring (IRR 3.26 for males with two affected parents, 4.52 for females).
      Similar patterns were seen for conviction for serious offences. Associations were
      attenuated after adjustment was made for family socio-economic position (SEP) and
      parental criminality. CONCLUSIONS: Offspring of parents with mental disorder
      represent a group at elevated risk of criminality. This raises the possibility of
      shared familial vulnerability for mental disorder and criminal behaviour, and
      highlights the need to consider early identification and intervention in this
      group.

PMID- 21846423
TI  - A latent class approach to the external validation of respiratory and non
      respiratory panic subtypes.
AB  - BACKGROUND: The phenotypic variance observed in panic disorder (PD) appears to be
      best captured by a respiratory and non-respiratory panic subtype. We compared
      respiratory and non-respiratory panic subtypes across a series of external
      validators (temporal stability, psychiatric co-morbidity, treatment response) to
      determine whether subtypes are best conceptualized as differing: (1) only on
      their symptom profiles with no other differences between them; (2) on a
      quantitative (i.e. severity) dimension only; or (3) qualitatively from one
      another. METHOD: Data from a large epidemiological survey (National Epidemiologic
      Survey on Alcohol and Related Conditions) and a clinical trial (Cross-National
      Collaborative Panic Study) were used. All analytic comparisons were examined
      within a latent class framework. RESULTS: High temporal stability of panic
      subtypes was observed, particularly among females. Respiratory panic was
      associated with greater odds of lifetime major depression and a range of anxiety
      disorders as well as increased treatment utilization, but no demographic
      differences. Treatment outcome data did not suggest that the two PD subtypes were
      associated with differential response to either imipramine or alprazolam.
      CONCLUSIONS: These data suggest that respiratory and non-respiratory panic
      represent valid subtypes along the PD continuum, with the respiratory variant
      representing a more severe form of the disorder.

PMID- 21846424
TI  - The lifetime impact of attention deficit hyperactivity disorder: results from the
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
AB  - BACKGROUND: The aim of the study was to present nationally representative data on
      the lifetime independent association between attention deficit hyperactivity
      disorder (ADHD) and psychiatric co-morbidity, correlates, quality of life and
      treatment seeking in the USA. METHOD: Data were derived from a large national
      sample of the US population. Face-to-face surveys of more than 34 000 adults aged
      18 years and older residing in households were conducted during the 2004-2005
      period. Diagnoses of ADHD, Axis I and II disorders were based on the Alcohol Use
      Disorder and Associated Disabilities Interview Schedule-DSM-IV version. RESULTS:
      ADHD was associated independently of the effects of other psychiatric co
      morbidity with increased risk of bipolar disorder, generalized anxiety disorder,
      post-traumatic stress disorder, specific phobia, and narcissistic, histrionic,
      borderline, antisocial and schizotypal personality disorders. A lifetime history
      of ADHD was also associated with increased risk of engaging in behaviors
      reflecting lack of planning and deficient inhibitory control, with high rates of
      adverse events, lower perceived health, social support and higher perceived
      stress. Fewer than half of individuals with ADHD had ever sought treatment, and
      about one-quarter had ever received medication. The average age of first
      treatment contact was 18.40 years. CONCLUSIONS: ADHD is common and associated
      with a broad range of psychiatric disorders, impulsive behaviors, greater number
      of traumas, lower quality of life, perceived social support and social
      functioning, even after adjusting for additional co-morbidity. When treatment is
      sought, it is often in late adolescence or early adulthood, suggesting the need
      to improve diagnosis and treatment of ADHD.

PMID- 21846425
TI  - A multi-site randomized controlled trial of a cognitive skills programme for male
      mentally disordered offenders: social-cognitive outcomes.
AB  - BACKGROUND: Cognitive skills programmes have been associated with improvements on
      psychometric measures and reductions in antisocial behaviour in mentally
      disordered offenders (MDOs). However, to date there have been no randomized
      controlled trials (RCTs) of such programmes with this population. In the first
      RCT of a cognitive skills programme with MDOs we aimed to determine if
      participation in the Reasoning and Rehabilitation (R&R) programme was associated
      with improvements in social-cognitive skills and thinking styles. METHOD: A total
      of 84 men with a primary diagnosis of psychotic disorder and a history of
      violence were recruited from medium-secure forensic units and allocated to
      receive R&R (n=44) or treatment as usual (TAU; n=40). At baseline and post
      treatment interviews, participants completed questionnaires to assess social
      problem-solving, criminal attitudes, anger experience, blame externalizing and
      perspective-taking. Researchers were not blind to group status. RESULTS: The R&R
      group demonstrated significant improvements on measures of social problem-solving
      relative to the TAU group, some of which were maintained at 12 months post
      treatment. Only half of those allocated to receive R&R completed the full
      programme. In post-hoc analyses programme completers showed improvements in
      social problem-solving at the end of treatment and changes in criminal attitudes
      at 12 months post-treatment. CONCLUSIONS: Among male MDOs, R&R participation was
      associated with improvements in social-cognitive skills, some of which were
      maintained for up to 12 months post-treatment. Our finding that programme
      completers do better may reflect pre-treatment patient characteristics. This
      study establishes that multi-site RCTs can be conducted in medium-secure forensic
      units.

PMID- 21846426
TI  - Guideline concordant monitoring of metabolic risk in people treated with
      antipsychotic medication: systematic review and meta-analysis of screening
      practices.
AB  - BACKGROUND: Despite increased cardiometabolic risk in individuals with mental
      illness taking antipsychotic medication, metabolic screening practices are often
      incomplete or inconsistent. METHOD: We undertook a systematic search and a PRISMA
      (Preferred Reporting Items for Systematic reviews and Meta-Analyses) meta
      analysis of studies examining routine metabolic screening practices in those
      taking antipsychotics both for patients in psychiatric care before and following
      implementation of monitoring guidelines. RESULTS: We identified 48 studies (n=290
      534) conducted between 2000 and 2011 in five countries; 25 studies examined
      predominantly schizophrenia-spectrum disorder populations; 39 studies (n=218 940)
      examined routine monitoring prior to explicit guidelines; and nine studies (n=71
      594) reported post-guideline monitoring. Across 39 studies, routine baseline
      screening was generally low and above 50% only for blood pressure [69.8%, 95%
      confidence interval (CI) 50.9-85.8] and triglycerides (59.9%, 95% CI 36.6-81.1).
      Cholesterol was measured in 41.5% (95% CI 18.0-67.3), glucose in 44.3% (95% CI
      36.3-52.4) and weight in 47.9% (95% CI 32.4-63.7). Lipids and glycosylated
      haemoglobin (HbA1c) were monitored in less than 25%. Rates were similar for
      schizophrenia patients, in US and UK studies, for in-patients and out-patients.
      Monitoring was non-significantly higher in case-record versus database studies
      and in fasting samples. Following local/national guideline implementation,
      monitoring improved for weight (75.9%, CI 37.3-98.7), blood pressure (75.2%, 95%
      CI 45.6-95.5), glucose (56.1%, 95% CI 43.4-68.3) and lipids (28.9%, 95% CI 20.3
      38.4). Direct head-to-head pre-post-guideline comparison showed a modest but
      significant (15.4%) increase in glucose testing (p=0.0045). CONCLUSIONS: In
      routine clinical practice, metabolic monitoring is concerningly low in people
      prescribed antipsychotic medication. Although guidelines can increase monitoring,
      most patients still do not receive adequate testing.

PMID- 21846427
TI  - Response to an unsolicited intervention offer to persons aged >= 75 years after
      screening positive for depressive symptoms: a qualitative study.
AB  - BACKGROUND: Screening can increase detection of clinically relevant depressive
      symptoms, but screen-positive persons are not necessarily willing to accept a
      subsequent unsolicited treatment offer. Our objective was to explore limiting and
      motivating factors in accepting an offer to join a "coping with depression"
      course, and perceived needs among persons aged >=75 years who screened positive
      for depressive symptoms in general practice. METHODS: In a randomized controlled
      trial, in which 101 persons who had screened positive for depressive symptoms
      were offered a "coping with depression" course, a sample of 23 persons were
      interviewed, of whom five (22%) accepted the treatment offer. Interview
      transcripts were coded independently by two researchers. RESULTS: All five
      individuals who accepted a place on the course felt depressed and/or lonely and
      had positive expectations about the course. The main reasons for declining to
      join the course were: not feeling depressed, or having negative thoughts about
      the course effect, concerns about group participation, or about being too old to
      change and learn new things. Although perceived needs to relieve depressive
      symptoms largely matched the elements of the course, most of those who had been
      screened were not (yet) prepared to accept an intervention offer. Many expressed
      the need to discuss this treatment decision with their general practitioner.
      CONCLUSIONS: Although the unsolicited treatment offer closely matched the
      perceived needs of people screening positive for depressive symptoms, only those
      who combined feelings of being depressed or lonely with positive expectations
      about the offered course accepted it. Treatment should perhaps be more
      individually tailored to the patient's motivational stage towards change, a
      process in which general practitioners can play an important role.

PMID- 21846428
TI  - Significant inverse associations of serum n-6 fatty acids with plasma plasminogen
      activator inhibitor-1.
AB  - Epidemiological studies suggested that n-6 fatty acids, especially linoleic acid
      (LA), have beneficial effects on CHD, whereas some in vitro studies have
      suggested that n-6 fatty acids, specifically arachidonic acid (AA), may have
      harmful effects. We examined the association of serum n-6 fatty acids with
      plasminogen activator inhibitor-1 (PAI-1). A population-based cross-sectional
      study recruited 926 randomly selected men aged 40-49 years without CVD during
      2002-2006 (310 Caucasian, 313 Japanese and 303 Japanese-American men). Plasma PAI
      1 was analysed in free form, both active and latent. Serum fatty acids were
      measured with gas-capillary liquid chromatography. To examine the association
      between total n-6 fatty acids (including LA and AA) and PAI-1, multivariate
      regression models were used. After adjusting for confounders, total n-6 fatty
      acids, LA and AA, were inversely and significantly associated with PAI-1 levels.
      These associations were consistent across three populations. Among 915 middle
      aged men, serum n-6 fatty acids had significant inverse associations with PAI-1.

PMID- 21846430
TI  - Parenteral amino acids v. dextrose infusion: an anabolic strategy to minimise the
      catabolic response to surgery while maintaining normoglycaemia in diabetes
      mellitus type 2 patients.
AB  - Loss of body protein and hyperglycaemia represent typical features of the stress
      response to surgery and anaesthesia. This appears to be particularly pronounced
      in patients with diabetes mellitus type 2. The aim of the present study was to
      highlight the greater benefit of amino acids (AA) as represented by positive
      protein balance and maintenance of blood glucose homoeostasis compared with
      dextrose (DEX) in diabetic patients after colorectal surgery. A total of thirteen
      patients underwent a 5 h stable isotope infusion study (2 h fasted, 3 h fed with
      an infusion of AA (n 6) or DEX (n 7)) on the second post-operative day. Glucose
      and protein kinetics were assessed by using the stable isotopes l-[1-13C]leucine
      and [6,6-2H2]glucose. The transition from fasted to fed state decreased
      endogenous glucose production (P < 0.001) in both groups, with a more profound
      effect in the DEX group (P = 0.031). In contrast, total glucose production was
      increased by the provision of DEX while being lowered by AA (P = 0.021). Feeding
      decreased protein oxidation (P = 0.009) and protein synthesis in the AA group,
      whereas DEX infusion did not affect oxidation and even decreased protein
      synthesis. Therefore, only AA shifted protein balance to a positive value, while
      patients in the DEX group remained in a catabolic state (P < 0.001). Parenteral
      nutritional support with AA rather than with DEX is an effective strategy to
      achieve a positive protein balance while maintaining normoglycaemia in diabetic
      patients after colorectal surgery.

PMID- 21846431
TI  - The morphology and genetic characterization of Iheringascaris goai n. sp.
      (Nematoda: Raphidascarididae) from the intestine of the silver whiting and
      spotted catfish off the central west coast of India.
AB  - In this study a new species of nematode, Iheringascaris goai n. sp., is reported
      from two fish hosts, including silver whiting, Sillago sihama, and spotted
      catfish, Arius maculatus, caught off the Central West Coast of India at Goa. The
      new species can be differentiated morphologically from I. inquies, the most
      closely related species collected from cohabiting marine fish. The distinguishing
      characteristics are distinct cuticular striations, a unilateral excretory system,
      the presence of dentigerous ridges on the inner margin of the lips and the ratio
      of oesophagus to body length. In males, the ratio of spicules to body length is
      higher and the number of pre-anal papillae is less in comparison to those in I.
      inquies. In addition, the tail curves ventrad in males, while in females, the
      vulva is post-equatorial. The sequence alignment of 18S rDNA and cytochrome c
      oxidase subunit I with sequences of known species selected from the same
      superfamily shows a significant difference. The morphological and molecular
      differences reported here can, therefore, be used to assign the specimen to a new
      species.

PMID- 21846432
TI  - Expect the unexpected: a case of pelvic splenosis.

PMID- 21846433
TI  - Risk homeostasis: balancing the biological and psychosocial effects of delayed
      childbearing.

PMID- 21846429
TI  - Vitamin D status among adolescents in Europe: the Healthy Lifestyle in Europe by
      Nutrition in Adolescence study.
AB  - An adequate vitamin D status is essential during childhood and adolescence, for
      its important role in cell growth, skeletal structure and development. It also
      reduces the risk of conditions such as CVD, osteoporosis, diabetes mellitus,
      infections and autoimmune disease. As comparable data on the European level are
      lacking, assessment of vitamin D concentrations was included in the Healthy
      Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. Fasting blood
      samples were obtained from a subsample of 1006 adolescents (470 males; 46.8 %)
      with an age range of 12.5-17.5 years, selected in the ten HELENA cities in the
      nine European countries participating in this cross-sectional study, and analysed
      for 25-hydroxycholecalciferol (25(OH)D) by ELISA using EDTA plasma. As specific
      reference values for adolescents are missing, percentile distribution were
      computed by age and sex. Median 25(OH)D levels for the whole population were 57.1
      nmol/l (5th percentile 24.3 nmol/l, 95th percentile 99.05 nmol/l). Vitamin D
      status was classified into four groups according to international guidelines
      (sufficiency/optimal levels >= 75 nmol/l; insufficiency 50-75 nmol/l; deficiency
      27.5-49.99 nmol/l and severe deficiency < 27.5 nmol/l). About 80 % of the sample
      had suboptimal levels (39 % had insufficient, 27 % deficient and 15 % severely
      deficient levels). Vitamin D concentrations increased with age (P < 0.01) and
      tended to decrease according to BMI. Geographical differences were also
      identified. Our study results indicate that vitamin D deficiency is a highly
      prevalent condition in European adolescents and should be a matter of concern for
      public health authorities.

PMID- 21846434
TI  - Planned vaginal delivery versus planned caesarean section: short-term medical
      outcome analyzed according to intended mode of delivery.
AB  - OBJECTIVE: To compare maternal medical outcome after planned vaginal delivery and
      planned Caesarean section. METHODS: We conducted a prospective cohort study of
      healthy primiparous women in Stockholm, Sweden, who were either scheduled for a
      planned Caesarean section (for breech presentation or at maternal request) or
      admitted for a vaginal delivery. Data were analyzed according to intended mode of
      delivery. RESULTS: A total of 541 women were included in the study; of these, 247
      had a Caesarean section and 294 a vaginal delivery. There were sociodemographic
      differences between the groups. No difference in mean estimated blood loss or
      rate of infection was found. Complications in the planned Caesarean section group
      were lower than previously reported. The difference in estimated blood loss
      between women undergoing planned Caesarean section and women who had a vaginal
      delivery was not more than 7%. Morbidity in the planned vaginal delivery group
      was mostly due to operative interventions. The Caesarean section group had a
      longer hospital stay than women who delivered vaginally. CONCLUSION: We found no
      difference in short-term medical outcomes between primiparous women undergoing
      planned Caesarean section and those undergoing planned vaginal delivery after
      analysis according to the intended mode of delivery.

PMID- 21846435
TI  - Using clinical symptoms to predict adverse maternal and perinatal outcomes in
      women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate
      of RiSk) study.
AB  - OBJECTIVES: Preeclampsia is a leading cause of maternal morbidity. The clinical
      challenge lies in predicting which women with preeclampsia will suffer adverse
      outcomes and would benefit from treatment, while minimizing potentially harmful
      interventions. Our aim was to determine the ability of maternal symptoms (i.e.,
      severe nausea or vomiting, headache, visual disturbance, right upper quadrant
      pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or
      dyspnea) to predict adverse maternal or perinatal outcomes. METHODS: We used data
      from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre,
      prospective cohort study designed to investigate the maternal risks associated
      with preeclampsia. Relative risks and receiver operating characteristic (ROC)
      curves were assessed for each preeclampsia symptom and outcome pair. RESULTS: Of
      2023 women who underwent assessment, 52% experienced at least one preeclampsia
      symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or
      perinatal outcome. No symptom and outcome pair, in either of the maternal or
      perinatal groups, achieved an area under the ROC curve value > 0.7, which would
      be necessary to demonstrate a discriminatory predictive value. CONCLUSION:
      Maternal symptoms of preeclampsia are not independently valid predictors of
      maternal adverse outcome. Caution should be used when making clinical decisions
      on the basis of symptoms alone in the preeclamptic patient.

PMID- 21846436
TI  - Risk factors for postpartum hemorrhage: can we explain the recent temporal
      increase?
AB  - OBJECTIVE: To assess risk factors for postpartum hemorrhage (PPH) and the extent
      to which changes in those risk factors may explain the rising incidence of PPH
      recently reported from industrialized countries. METHODS: We carried out a
      hospital-based cohort study of 103 726 consecutive deliveries from January 1,
      1978, to January 31, 2007, from the computerized medical records of a tertiary
      care university maternity hospital in Montreal. We examined adjusted odds ratios
      for any PPH (estimated blood loss > 500 mL for vaginal deliveries, > 1000 mL for
      Caesarean sections), severe PPH (estimated blood loss >= 1500 mL), and PPH
      accompanied by blood transfusion and/or hysterectomy. RESULTS: Major independent
      risk factors for PPH included primiparity, prior Caesarean section, placenta
      previa or low-lying placenta, marginal umbilical cord insertion in the placenta,
      transverse lie, labour induction and augmentation, uterine or cervical trauma at
      delivery, gestational age < 32 weeks, and birth weight >= 4500 g. An overall
      increase in rate of PPH over the study period (OR 1.029; 95% CI 1.024 to 1.034
      per year) disappeared (OR 0.995; 95% CI 0.988 to 1.001 per year) after inclusion
      of maternal age, parity, prior Caesarean section, labour induction and
      augmentation, placenta previa or low-lying placenta, and abnormal placenta, with
      most of the reduction attributable to rises in previous Caesarean section and
      labour augmentation. CONCLUSION: Labour induction, augmentation of labour, and
      prior Caesarean section are significantly associated with the risk of PPH, and
      their increase over the study period largely explains the observed rise in PPH.

PMID- 21846437
TI  - Comparison of demographic and obstetric characteristics of Canadian primiparous
      women of advanced maternal age and younger age.
AB  - OBJECTIVE: The rate of pregnancy at advanced maternal age (AMA) has increased
      during recent decades. The purpose of this study is to compare demographic and
      obstetric characteristics of Canadian primiparous women of AMA with those aged 20
      to 29 years. METHODS: We conducted a secondary analysis of data collected through
      the national Maternity Experiences Survey (MES) of the Canadian Perinatal
      Surveillance System. The sample included 301 primiparous women aged 35 years or
      over and 1,564 primiparous women aged 20 to 29 years. Estimates of prevalence for
      each group and their odds ratios were calculated using sample weights of the
      survey, and variances were calculated using bootstrapping methods adjusting for
      sampling design and weights. RESULTS: Women of AMA were significantly more likely
      to be better educated, to have higher income, to be employed, and to continue to
      work until the end of pregnancy than younger women. They also reported having
      significantly more information on pregnancy, labour, and birth, and they were
      more likely to attend prenatal classes. They were more likely to have had a
      miscarriage or infertility treatment, to request or be offered a Caesarean
      section, and to have a higher rate of Caesarean section. There were no
      significant differences in rates of preterm birth, low birth weight, and small
      for-gestational age infants. CONCLUSION: Pregnant women of AMA differ from
      younger women in demographic characteristics, knowledge level, and some health
      behaviours and pregnancy outcomes. The growing number of pregnancies at AMA
      indicates the need for developing appropriate care plans to address the specific
      needs of this group.

PMID- 21846438
TI  - Economic burden of surgically confirmed endometriosis in Canada.
AB  - OBJECTIVE: To estimate the societal economic burden of illness caused by
      surgically confirmed endometriosis in Canada in 2009, including direct health
      care costs, lost productivity, and lost leisure time costs. METHODS: Using a
      cross-sectional design, direct health care resource use data were obtained from
      nine family physicians and nine gynaecologists from across Canada, who were
      experienced in the treatment of women with surgically confirmed endometriosis.
      Data on alternative treatments and health care providers, as well as work
      absenteeism, lost leisure time, and caregiver time were obtained from a
      convenience sample of 27 women with endometriosis treated at two gynaecology
      clinics in Alberta and Quebec. Unit costs were assigned to resource use items for
      treatment-seeking patients, and total costs for each resource use item were
      aggregated to estimate the societal costs of endometriosis in Canada in 2009,
      across all prevalent cases of surgically confirmed endometriosis. RESULTS: The
      estimated mean annual societal cost of endometriosis was $5,200 per patient (95%
      CI $3,700 to $7,100), with lost productivity and lost leisure time costs
      accounting for 78%. Extrapolating these figures yields an estimated total annual
      cost to Canadian society of $1.8 billion (95% CI $1.3 billion to $2.4 billion)
      attributable to surgically confirmed endometriosis in Canada. CONCLUSION: For
      some women, surgically confirmed endometriosis has a substantial negative impact
      that can result in suffering to the individual and her family, and lead to
      substantial productivity losses. Understanding the interplay between direct
      costs, lost productivity, and quality of life is critical for accurately
      identifying and evaluating effective treatments for this condition.

PMID- 21846439
TI  - [Evaluation of an estrogen vaginal cream for the treatment of dyspareunia: a
      double-blind randomized trial].
AB  - OBJECTIVE: Our objective was to assess the short-term effect of an estrogen cream
      on symptoms associated with provoked vestibulodynia. METHODS: We undertook a
      double-blind randomized trial in women who had experienced dyspareunia satisfying
      the Friedrichcriteria for at least three months. We compared the daily
      application of 3 g of vaginal cream containing 1.875 g of conjugated estrogens
      for six weeks (estrogen group) with the application of a comparable cream without
      estrogens (placebo group). The main outcome was modification of
      dyspareunia,determined by a visual analogue scale of pain from the pretreatment
      period to the post-treatment period. Secondary outcomes were colposcopic
      evaluation of the vulva and pain reported during the swab test. RESULTS: Of 69
      women randomized, 61 participated for the full duration of the trial. Dyspareunia
      was significantly lessened in both groups (estrogen group: 7.4 +/- 1.9 pre
      treatment vs. 4.8 +/- 3.0 post-treatment, P < 0. 01; placebo group:7.1 +/- 1.9
      vs. 4.9 +/- 2. 7, P < 0.01), but the difference observed in terms of decrease
      between the two groups was not found to be significant (P = 0.5). Alternatively,
      the group treated with estrogen cream showed (1) a more substantial decrease of
      the pain reported at the orifices of the Bartholin's glands when palpated with a
      swab (P < 0.01), and (2) a decrease of the inflammation observed at the orifices
      of the Bartholin's glands orifices and the posterior fourchette (P < 0.01).
      CONCLUSION: Applying a vaginal cream, whether it contains estrogens or not, for
      six weeks lessens dyspareunia. Adding estrogens to such a cream could facilitate
      a decrease of the inflammation observed at the orifices of the Bartholin's glands
      and the vestibule.

PMID- 21846440
TI  - Preoperative serum CA 125 level as a predictor for metastasis and survival in
      endometrioid endometrial cancer.
AB  - OBJECTIVE: We wished to determine the relationship between preoperative serum CA
      125 levels and the risk of metastatic disease, recurrent disease, and death in
      women with endometrial cancer. METHODS: We reviewed the records of women with
      endometrial adenocarcinoma of all stages who underwent primary surgery. We
      abstracted multiple data variables, including demographic characteristics, serum
      CA 125 levels, postoperative histopathology results, progression-free survival,
      and overall survival rates. RESULTS: The records of 97 women with endometrial
      carcinoma were analyzed. With a serum CA 125 cut-off level of 35 kU/L, the
      likelihood of disease-related death could be predicted with 70% sensitivity and
      83% specificity; disease progression could be predicted with 60% sensitivity and
      84% specificity; and lymph node metastasis could be predicted with 75%
      sensitivity and 84% specificity. There was a significant relationship between a
      serum CA 125 level >= 35 kU/L and depth of myometrial invasion, cervical stromal
      invasion, stage, frequency of recurrence, and disease-related death. Having deep
      myometrial invasion, cervical stromal involvement, positive peritoneal cytology,
      lymph node metastasis, disease recurrence, and disease-related death were each
      associated with significantly higher mean CA 125 levels. In women with serum CA
      125 levels < 35 kU/L, five-year progression-free survival rates (88%) and overall
      survival rates (92%) were significantly better than in women with levels >= 35
      kU/L (57% and 70%, respectively; P = 0.001 for both). CONCLUSION: Serum CA 125
      levels and extension of disease are highly correlated in women with endometrioid
      endometrial cancer, and elevated CA 125 levels predict a higher risk of disease
      recurrence and death.

PMID- 21846441
TI  - Maternal atrial arrhythmia detected by uterine artery Doppler.
AB  - BACKGROUND: Uterine artery Doppler ultrasound assessment is used to assess
      uteroplacental blood flow and the risk of placental ischemic-thrombotic injury in
      high-risk pregnancies. We report here a case in which this examination identified
      the presence of a maternal atrial arrhythmia. CASE: A 50-year-old woman with no
      significant past medical history received antenatal care in our fetal medicine
      unit clinic because of advanced maternal age, a history of recurrent pregnancy
      loss, multiple uterine fibroids, and a history of in vitro fertilization using
      donated oocytes. Uterine artery Doppler ultrasound was normal at 19 weeks, but
      was repeated at 33 weeks because of abnormal placental texture and maternal
      risks, revealing an irregular maternal heart rhythm. Paroxysmal atrial
      fibrillation was confirmed by Holter monitor at 34 weeks. The patient was
      asymptomatic and declined the cardiologist's recommendation of antepartum and
      postpartum anticoagulation. She remained asymptomatic and had delivery by
      Caesarean section at term. CONCLUSION: Uterine artery Doppler flow studies may
      identify a significant maternal cardiac arrhythmia.

PMID- 21846442
TI  - A rare case of cardiac rhabdomyomas in a dizygotic twin pair.
AB  - Cardiac rhabdomyoma (CR) is the cardiac tumour most commonly diagnosed in utero.
      Eighty percent of CRs are associated with tuberous sclerosis (TS). TS is a rare
      multi-system disease, with autosomal dominant genetic transmission. If the
      parents of an affected child do not have features of TS, then either one parent
      is mosaic for the TS gene mutation or the affected child is the result of a de
      novo germline mutation. We present a case of a dizygotic twin pregnancy
      complicated by CRs in both fetuses at 24 weeks. Twin A died in utero at 28 weeks.
      Preterm labour and delivery of twin B occurred at 33 weeks. Twin B had multiple
      small CRs and a large apical CR. At six weeks after delivery, the CRs had
      disappeared or reduced in size. Regression in the third trimester or postnatally
      is the natural course of CRs. Molecular testing for TS identified two variants in
      the TSC2 gene. The parents were clinically unaffected; however, the father was
      subsequently found on an MRI of the head to have cortical tubers, and he was
      found to carry the pathogenic TSC2 mutation. Since dizygotic twin pregnancy is
      akin to two consecutive pregnancies, the etiology in our case is due to one
      parent having subclinical TS. To the best of our knowledge, this is the first
      such case to be reported.

PMID- 21846443
TI  - The American Heart Association 2010 guidelines for the management of cardiac
      arrest in pregnancy: consensus recommendations on implementation strategies.

PMID- 21846444
TI  - Maternity leave in normal pregnancy.
AB  - OBJECTIVE: To assist maternity care providers in recognizing and discussing
      health- and illness-related issues in pregnancy and their relationship to
      maternity benefits. EVIDENCE: Published literature was retrieved through searches
      of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 using appropriate
      controlled vocabulary (e.g., maternity benefits) and key words (e.g., maternity,
      benefits, pregnancy). Results were restricted to systematic reviews, randomized
      controlled trials/controlled clinical trials, and observational studies. There
      were no date or language restrictions. Searches were updated on a regular basis
      and incorporated in the guideline to December 2009. Grey (unpublished) literature
      was identified through searching the web sites of health technology assessment
      and health technology assessment-related agencies, clinical practice guideline
      collections, clinical trial registries, and national and international medical
      specialty societies.

PMID- 21846445
TI  - Sexual and reproductive health counselling by health care professionals.

PMID- 21846446
TI  - Vaginal blue bullae.

PMID- 21846447
TI  - Factors associated with lower uterine segment thickness near term in women with
      previous caesarean section.
AB  - OBJECTIVE: To estimate the association between potential influencing factors and
      lower uterine segment (LUS) thickness at term in women with previous Caesarean
      section. METHODS: We conducted a cohort study of women with previous low
      transverse Caesarean section undergoing ultrasonographic measurement of LUS
      thickness between 35 and 38 weeks' gestation in a tertiary care centre between
      2006 and 2009. Measurements of the full LUS thickness and the myometrial LUS
      thickness were performed both transabdominally and transvaginally. The thinnest
      measurements for both full and myometrial LUS thicknesses were considered
      dependent variables. Non-parametric analyses, multivariate linear regression
      analyses, and multivariate regression analyses were used to evaluate the
      relationships between LUS thickness and the potential influencing factors of
      maternal age, interdelivery interval, prior vaginal delivery, and several
      characteristics of the previous Caesarean section. RESULTS: In 377 women who
      underwent measurement of LUS thickness, labour before previous Caesarean section
      was the only characteristic associated with a greater full LUS thickness (an
      additional 0.9 mm; 95% CI 0.5 to 1.2 mm) in multivariate linear regression
      analysis. Labour before previous Caesarean section (0.5 mm; 95% CI 0.2 to 0.7 mm)
      and the use of synthetic sutures (as opposed to catgut sutures) for the closure
      of the previous hysterotomy incision (0.3 mm; 95% CI 0.02 to 0.5 mm) were the
      only two variables significantly associated with a thicker myometrial LUS. In
      multivariate regression analysis, three factors were predictive of a full LUS
      thickness of > 2.3 mm: the presence of labour, a recurrent indication for
      Caesarean section, and the use of synthetic sutures for hysterotomy closure at
      previous Caesarean section (P < 0.05). CONCLUSION: Labour at the time of previous
      Caesarean section is associated with a thicker LUS near term in the subsequent
      pregnancy. The use of synthetic sutures for hysterotomy closure is another factor
      potentially associated with a thicker LUS.

PMID- 21846448
TI  - PIERS proteinuria: relationship with adverse maternal and perinatal outcome.
AB  - OBJECTIVE: To examine the ability of three different proteinuria assessment
      methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24
      hour urine collection) to predict adverse pregnancy outcomes. METHODS: We
      performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated
      Estimate of RiSk), in seven academic tertiary maternity centres practising
      expectant management of preeclampsia remote from term in Canada, New Zealand, and
      Australia. Eligible women were those admitted with preeclampsia who had at least
      one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio,
      and/or 24-hour urine collection. Proteinuria assessment was done either visually
      at the bedside (by dipstick) or by hospital clinical laboratories for spot urine
      Pr/Cr and 24-hour urine collection. We calculated receiver operating
      characteristic area under the curve (95% CI) for each proteinuria method and each
      of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal
      outcomes (at any time). Models with AUC >= 0.70 were considered of interest.
      Analyses were run for all women who had each type of proteinuria assessment and
      for a cohort of women ("ALL measures") who had all three proteinuria assessments.
      RESULTS: More women were proteinuric by urinary dipstick (>= 2+, 61.4%) than by
      spot urine Pr/Cr (>= 30 g/mol, 50.4%) or 24-hour urine collection (>= 0.3g/d,
      34.7%). Each proteinuria measure evaluated had some discriminative power, and
      dipstick proteinuria (categorical) performed as well as other methods. No single
      method was predictive of adverse perinatal outcome. CONCLUSION: The measured
      amount of proteinuria should not be used in isolation for decision-making in
      women with preeclampsia. Dipstick proteinuria performs as well as other methods
      of assessing proteinuria for prediction of adverse events.

PMID- 21846449
TI  - Birth technology and maternal roles in birth: knowledge and attitudes of canadian
      women approaching childbirth for the first time.
AB  - OBJECTIVE: To describe Canadian nulliparous women's attitudes to birth technology
      and their roles in childbirth. METHODS: A large convenience sample of low-risk
      women expecting their first birth was recruited by posters in laboratories, at
      the offices of obstetricians, family physicians, and midwives, at prenatal
      classes, and through web-based advertising and invited to complete a paper or web
      based questionnaire. RESULTS: Of the 1318 women completing the questionnaire, 95%
      did so via the web-based method; 13.2% of respondents were in the first
      trimester, 39.8% were in the second trimester, and 47.0% in the third. Overall,
      42.6% were under the care of an obstetrician, 29.3% a family physician, and 28.1%
      a registered midwife. The sample included mainly well-educated, middle-class
      women. The planned place of giving birth ranged from home to hospital, and from
      rural centres to large city hospitals. Eighteen percent planned to engage a
      doula. Women attending obstetricians reported attitudes more favourable to the
      use of birth technology and less supportive of women's roles in their own
      delivery, regardless of the trimester in which the survey was completed. Those
      women attending midwives reported attitudes less favourable to the use of
      technology at delivery and more supportive of women's roles. Family practice
      patients' opinions fell between the other two groups. For eight of the questions,
      "I don't know" (IDK) responses exceeded 15%. These IDK responses were most
      frequent for questions regarding risks and benefits of epidural analgesia,
      Caesarean section, and episiotomy. Women in the care of midwives consistently
      used IDK options less frequently than those cared for by physicians. CONCLUSIONS:
      Regardless of the type of care provider they attended, many women reported
      uncertainty about the benefits and risks of common procedures used at childbirth.
      When grouped by the type of care provider, in all trimesters, women held
      different views across a range of childbirth issues, suggesting that the three
      groups of providers were caring for different populations with different
      attitudes and expectations.

PMID- 21846450
TI  - Multiple births associated with assisted human reproduction in Canada.
AB  - OBJECTIVE: Assisted human reproduction has been associated with increased rates
      of multiple births. Data suggest that twins and higher order multiple pregnancies
      are at risk for pre- and postnatal health complications that contribute to stress
      on both the family and the Canadian health care system. No published Canadian
      data estimate the contribution of assisted human reproduction to multiple birth
      rates. This study was designed to determine the contributions of age and assisted
      human reproduction to multiple birth rates in Canada. METHODS: We performed
      analyses of existing Canadian databases, using a mathematical model from the
      Centers for Disease Control and Prevention. More specifically, data from the
      Canadian Vital Statistics: Births and Stillbirths database were combined with
      data from the Canadian Assisted Reproductive Technologies Register collected by
      the Canadian Fertility and Andrology Society. Datasets were standardized to age
      distributions of mothers in 1978. RESULTS: RESULTS suggest that in vitro
      fertilization, ovulation induction, and age each contribute more to the rates of
      triplets than to twins. As expected, the contribution of natural factors was
      higher to twins than to triplets. CONCLUSION: These are the first Canadian data
      analyzed to separate and measure the contributions of age and assisted
      reproductive technologies to multiple birth rates. Our findings are important for
      guiding physician and patient education and informing the development of
      treatment protocols that will result in lower-risk pregnancies and improved long
      term health for women and their offspring.

PMID- 21846451
TI  - Risk factors for ectopic pregnancy after in vitro fertilization treatment.
AB  - OBJECTIVE: To identify risk factors for ectopic pregnancy after in vitro
      fertilization treatment. METHODS: We conducted a study among women who conceived
      after IVF treatment and evaluated the possible risk factors for ectopic
      pregnancy. The parameters evaluated were demographics of the patients, cause of
      infertility, and risk factors for ectopic pregnancy, including tubal infertility
      and previous ectopic pregnancy. RESULTS: Of 365 women, 18 women had an ectopic
      pregnancy and 347 others had an intrauterine pregnancy (control group). The
      incidence of IVF ectopic pregnancy was 4.9%. The mean age was 34.2 +/- 1.4 years
      in the ectopic group and 34.3 +/- 0.2 years in the control group; mean BMI was
      23.8 +/- 1.0 in the ectopic group and 24.5 +/- 0.9 in the control group. Previous
      ectopic pregnancy, previous IVF ectopic pregnancy, or smoking did not affect the
      occurrence of ectopic pregnancy in this population. Logistic regression analysis
      demonstrated that tubal factor infertility and previous surgery for endometriosis
      were risk factors for IVF ectopic pregnancy. CONCLUSION: Tubal factor infertility
      and previous surgery for endometriosis appear to be risk factors for ectopic
      pregnancy after IVF treatment. Other factors that usually contribute to
      spontaneous ectopic pregnancy, including previous ectopic pregnancy, pelvic
      infection, and smoking, were not risk factors for IVF ectopic pregnancy in our
      study.

PMID- 21846452
TI  - Full-term pregnancy and vaginal delivery after treatment for non-Hodgkin's
      lymphoma of the cervix and lower uterine segment: a case report.
AB  - BACKGROUND: Primary gynaecologic non-Hodgkin's lymphomas are rare. We present a
      case of primary large B-cell lymphoma localized to the lower uterine segment and
      endocervical stroma that was successfully treated with chemotherapy and
      immunotherapy. Treatment was followed by a disease-free interval and successful
      term vaginal delivery. CASE: A 21-year-old nulliparous woman presented with
      dysfunctional uterine bleeding. Radiologic assessment of a posterior lower
      uterine segment mass and pathologic evaluation of cervical biopsies demonstrated
      diffuse large B-cell lymphoma involving the endocervical stroma. The patient was
      treated with chemotherapy and immunotherapy. She had a normal, uncomplicated full
      term pregnancy and spontaneous vaginal delivery six years after treatment.
      CONCLUSION: Aggressive diagnosis and treatment of primary non-Hodgkin's lymphomas
      of the cervix do not preclude the possibility of a successful pregnancy and term
      vaginal delivery.

PMID- 21846453
TI  - Partial herniation through the peritoneal defect of a pfannenstiel incision: a
      rare complication of non-closure.
AB  - BACKGROUND: The Pfannenstiel incision is used almost invariably in Caesarean
      section. With Caesarean section rates increasing, the Pfannenstiel is a commonly
      performed incision. The prevailing recommendation is not to close the peritoneum
      when closing a Pfannenstiel incision, and peritoneal non-closure does not appear
      to statistically influence postoperative complication rates. CASE: A 33-year-old
      woman presented with severe, intermittent lower abdominal pain one year after a
      Caesarean section. Laparoscopy showed a hernial defect at the Pfannenstiel
      incision, between the left rectus abdominis muscle and the anterior rectus
      sheath. Mesh repair was performed with uncomplicated postoperative outcome.
      CONCLUSION: The current case illustrates that complications specific to non
      closure of the peritoneum do arise. We advocate that laparoscopy should be
      considered for any patient with persistent, severe, or atypical pain following a
      Pfannenstiel incision.

PMID- 21846454
TI  - Is there a place for AMH testing in Canada?
AB  - Anti-mullerian hormone (AMH) is a glycoprotein traditionally known for its role
      in male sexual differentiation. More recently, AMH has been studied for its role
      in ovarian folliculogenesis and as a potential marker of ovarian reserve. A
      number of studies have suggested that measurement of serum AMH is a superior test
      of ovarian reserve because it is highly associated with the number of antral
      follicles, has little cycle variability, and declines throughout the reproductive
      lifespan. There is also evidence supporting the ability of AMH levels to predict
      age of menopause. Other studies have shown that measurement of serum AMH can
      predict responsiveness to ovarian follicular stimulation and the risk for ovarian
      hyperstimulation syndrome in women undergoing in vitro fertilization. Given the
      variety of potential applications and favourable test characteristics, it is
      reasonable to ask whether there is a place for providing universal AMH testing in
      Canada.

PMID- 21846455
TI  - Sexual and reproductive health, rights, and realities and access to services for
      first nations, inuit, and metis in Canada.

PMID- 21846456
TI  - Ultrasound in twin pregnancies.
AB  - OBJECTIVE: To review the literature with respect to the use of diagnostic
      ultrasound in the management of twin pregnancies. To make recommendations for the
      best use of ultrasound in twin pregnancies. OUTCOMES: Reduction in perinatal
      mortality and morbidity and short- and long-term neonatal morbidity in twin
      pregnancies. Optimization of ultrasound use in twin pregnancies. EVIDENCE:
      Published literature was retrieved through searches of PubMed and the Cochrane
      Library in 2008 and 2009 using appropriate controlled vocabulary (e.g., twin,
      ultrasound, cervix, prematurity) and key words (e.g., acardiac, twin, reversed
      arterial perfusion, twin-to-twin transfusion syndrome, amniotic fluid). Results
      were restricted to systematic reviews, randomized control trials/controlled
      clinical trials, and observational studies. There were no date restrictions.
      Studies were restricted to those with available English or French abstracts or
      text. Searches were updated on a regular basis and incorporated into the
      guideline to September 2009. Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and health technology
      assessment-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      VALUES: The evidence collected was reviewed by the Diagnostic Imaging Committee
      of the Society of Obstetricians and Gynaecologists of Canada, with input from
      members of the Maternal Fetal Medicine Committee and the Genetics Committee of
      the SOGC. The recommendations were made according to the guidelines developed by
      The Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND
      COSTS: The benefit expected from this guideline is facilitation and optimization
      of the use of ultrasound in twin pregnancy. SUMMARY STATEMENTS: 1. There are
      insufficient data to make recommendations on repeat anatomical assessments in
      twin pregnancies. Therefore, a complete anatomical survey at each scan may not be
      needed following a complete and normal assessment. (III) 2. There are
      insufficient data to recommend a routine preterm labour surveillance protocol in
      terms of frequency, timing, and optimal cervical length thresholds. (II-2) 3.
      Singleton growth curves currently provide the best predictors of adverse outcome
      in twins and may be used for evaluating growth abnormalities. (III) 4. It is
      suggested that growth discordance be defined using either a difference (20 mm) in
      absolute measurement in abdominal circumference or a difference of 20% in
      ultrasound-derived estimated fetal weight. (II-2) 5. Although there is
      insufficient evidence to recommend a specific schedule for ultrasound assessment
      of twin gestation, most experts recommend serial ultrasound assessment every 2 to
      3 weeks, starting at 16 weeks of gestation for monochorionic pregnancies and
      every 3 to 4 weeks, starting from the anatomy scan (18 to 22 weeks) for
      dichorionic pregnancies. (II-1) 6. Umbilical artery Doppler may be useful in the
      surveillance of twin gestations when there are complications involving the
      placental circulation or fetal hemodynamic physiology. (II-2) 7. Although many
      methods of evaluating the level of amniotic fluid in twins (deepest vertical
      pocket, single pocket, amniotic fluid index) have been described, there is not
      enough evidence to suggest that one method is more predictive than the others of
      adverse pregnancy outcome. (II-3) 8. Referral to an appropriate high-risk
      pregnancy centre is indicated when complications unique to twins are suspected on
      ultrasound. (II-2) These complications include: 1. Twin-to-twin transfusion
      syndrome 2. Monoamniotic twins gestation 3. Conjoined twins 4. Twin reversed
      arterial perfusion sequence 5. Single fetal death in the second or third
      trimester 6. Growth discordance in monochorionic twins. Recommendations 1. All
      patients who are suspected to have a twin pregnancy on first trimester physical
      examination or who are at risk (e.g., pregnancies resulting from assisted
      reproductive technologies) should have first trimester ultrasound performed. (II
      2A) 2. Every attempt should be made to determine and report amnionicity and
      chorionicity when a twin pregnancy is identified. (II-2A) 3. Although the
      accuracy in confirmation of gestational age at the first and second trimester is
      comparable, dating should be done with first trimester ultrasound. (II-2A) 4.
      Beyond the first trimester, it is suggested that a combination of parameters
      rather than a single parameter should be used to confirm gestational age. (II-2C)
      5. When twin pregnancy is the result of in vitro fertilization, accurate
      determination of gestational age should be made from the date of embryo transfer.
      (II-1A) 6. There is insufficient evidence to make a recommendation of which fetus
      (when discordant for size) to use to date a twin pregnancy. However, to avoid
      missing a situation of early intrauterine growth restriction in one twin, most
      experts agree that the clinician may consider dating pregnancy using the larger
      fetus. (III-C) 7. In twin pregnancies, aneuploidy screening using nuchal
      transluscency measurements should be offered. (II-2B) 8. Detailed ultrasound
      examination to screen for fetal anomalies should be offered, preferably between
      18 and 22 weeks' gestation, in all twin pregnancies. (II-2B) 9. When ultrasound
      is used to screen for preterm birth in a twin gestation, endovaginal ultrasound
      measurement of the cervical length should be performed. (II-2A) 10. Increased
      fetal surveillance should be considered when there is either growth restriction
      diagnosed in one twin or significant growth discordance. (II-2A) 11. Umbilical
      artery Doppler should not be routinely offered in uncomplicated twin pregnancies.
      (I-E) 12. For defining oligohydramnios and polyhydramnios, the ultrasonographer
      should use the deepest vertical pocket in either sac: oligohydramnios when < 2 cm
      and polyhydramnios when > 8 cm. (II-2B).

PMID- 21846459
TI  - Hypodontia and microdontia: clinical features of a rare syndrome.

PMID- 21846458
TI  - Treatment of severe inflammatory root resorption in a young permanent incisor
      with mineral trioxide aggregate.
AB  - Inflammatory root resorption is a pathologic condition caused by several
      etiologic factors including traumatic dental injury. In this case report, we
      describe treatment of a maxillary lateral incisor affected by severe, perforating
      inflammatory root resorption. An 11-year-old patient presented with a previously
      traumatized, root-filled maxillary lateral incisor associated with pain, mobility
      and a sinus tract. Radiographic examination revealed a large periradicular lesion
      involving pathologic resorption of the apical region of the root. After removal
      of the root canal filling, the tooth was treated with intracanal calcium
      hydroxide for 2 weeks. The calcium hydroxide dressing was then removed and the
      entire root canal was filled with mineral trioxide aggregate. The endodontic
      access cavity was restored with composite resin. After 1 year, advanced osseous
      healing of the periradicular region had occurred and no clinical symptoms were
      apparent.

PMID- 21846460
TI  - Analysis of clinical results of systemic antimicrobials combined with nonsurgical
      periodontal treatment for generalized aggressive periodontitis: a pilot study.
AB  - OBJECTIVE: To assess the clinical benefit of either metronidazole and amoxicillin
      or doxycycline administered immediately after completion of full-mouth scaling
      and root planing (FRP) for treatment of generalized aggressive periodontitis.
      METHODS: Patients, 18 to 40 years of age, referred to the Karadeniz Technical
      University department of periodontology between January 2009 and September 2009
      were randomly chosen for inclusion in the study if radiographic examination
      showed they had >= 20 teeth, clinical attachment loss and a probing pocket depth
      (PPD) >= 6 mm at 2 sites in >= 12 teeth, >= 3 of which were not first molars or
      incisors. Patients were divided into 3 groups and received FRP alone, FRP
      combined with metronidazole and amoxicillin, or FRP combined with doxycycline.
      PPD, clinical attachment level, gingival index, gingival bleeding index and
      plaque index values were measured at baseline and 2 months after treatment.
      RESULTS: Thirty-eight patients with untreated generalized aggressive
      periodontitis participated in the study. In all 3 groups, the periodontal index
      values 2 months after treatment were significantly lower than baseline values (p
      < 0.05). Values for PPD and clinical attachment level were more improved in the
      antibiotic groups than in the FRP group, and more improved in the metronidazole
      and amoxicillin group than in the doxycycline group (p < 0.05). However, no
      statistically significant intergroup difference was observed in the other
      clinical parameters (p > 0.05). Systemic use of metronidazole and amoxicillin or
      doxycycline was clinically superior to FRP for reducing PPDs >= 7 mm (p < 0.05).
      CONCLUSION: Treatment of generalized aggressive periodontitis with FRP alone or
      FRP combined with systemic antibiotics provided significant clinical benefits
      that reduced the need for periodontal surgery. Both antibiotic treatments had
      additional clinical benefits over those of FRP alone.

PMID- 21846461
TI  - Quality of life of patients after allogeneic hematopoietic stem cell
      transplantation with antihuman thymocyte globulin.
AB  - The utility of graft-versus-host disease (GVHD) prophylaxis with cyclosporine
      (CSA), methotrexate (MTX), and antihuman thymocyte globulin (ATG) after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) exists in the
      literature; however, up to now, it has not yet been fully described. This study
      was to observe the influence of adding ATG on GVHD prophylaxis and the quality of
      life (QoL) of 96 hemopathic patients after allo-HSCT. We retrospectively analyzed
      the outcomes of 96 consecutive patients undergoing allo-HSCT, including 54
      patients who received ATG regimen without in vitro T cell depletion (TCD) (ATG
      group) and 42 patients who received neither ATG regimen nor TCD (control group).
      All patients were followed up, and the factors, including age, sex, HLA and ABO
      compatibility, related and unrelated donors, and disease status, were undertaken
      to analysis. All patients in the study achieved trilineage engraftment with full
      donor chimerism. The cumulative incidence of acute GVHD (aGVHD) was lower in the
      ATG group than that in the control group (29.6% versus 57.1%, P = .006), and the
      cumulative incidence of chronic GVHD (cGVHD) was 35.2% for patients with ATG and
      66.7% for patients without ATG (P < .01). Notably, the proportion of patients
      with Karnofsky scores of >90 was 70.4% in the patients with ATG, and 28.6% in the
      patients without ATG (P < .001). Furthermore, the cumulative incidence of
      patients with opportunistic infection was significantly different in both groups
      posttransplantation, with 44.4% and 19.1% in recipient patients with or without
      ATG respectively (P < .05). Additional usage of ATG not only decreases the
      occurrence of aGVHD and cGVHD, but also improves QoL of patients after allo-HSCT
      without affecting stem cell engraftment or overall survival.

PMID- 21846462
TI  - Syntrophin isoforms play specific functional roles in the alpha1D-adrenergic
      receptor/DAPC signalosome.
AB  - alpha(1D)-Adrenergic receptors, key regulators of cardiovascular system function,
      are organized as a multi-protein complex in the plasma membrane. Using a Type-I
      PDZ-binding motif in their distal C-terminal domain, alpha(1D)-ARs associate with
      syntrophins and dystrophin-associated protein complex (DAPC) members utrophin,
      dystrobrevin and alpha-catulin. Three of the five syntrophin isoforms (alpha,
      beta(1) and beta(2)) interact with alpha(1D)-ARs and our previous studies suggest
      multiple isoforms are required for proper alpha(1D)-AR function in vivo. This
      study determined the contribution of each specific syntrophin isoform to
      alpha(1D)-AR function. Radioligand binding experiments reveal alpha-syntrophin
      enhances alpha(1D)-AR binding site density, while phosphoinositol and ERK1/2
      signaling assays indicate beta(2)-syntrophin augments full and partial agonist
      efficacy for coupling to downstream signaling mechanisms. The results of this
      study provide clear evidence that the cytosolic components within the alpha(1D)
      AR/DAPC signalosome significantly alter the pharmacological properties of
      alpha(1)-AR ligands in vitro.

PMID- 21846463
TI  - 10-Gingerol, a component of rikkunshito, improves cisplatin-induced anorexia by
      inhibiting acylated ghrelin degradation.
AB  - Rikkunshito (RKT), a Japanese traditional medicine, has been shown to stimulate
      food intake in rats with cisplatin-induced anorexia; however, the underlying
      mechanisms remain unknown. In this study, we investigated whether RKT is involved
      in the degradation of peripheral ghrelin. RKT inhibited decreases in plasma
      ghrelin level and enhanced acyl- to desacyl-ghrelin (A/D) ratio in cisplatin
      treated rats. Several components of RKT demonstrated inhibitory activity against
      ghrelin deacylating enzymes. In addition, 10-gingerol, a component of RKT,
      inhibited exogenous ghrelin deacylation. Therefore, RKT may enhance plasma acyl
      ghrelin level, at least in part, by inhibiting the circulating ghrelin degrading
      enzyme.

PMID- 21846464
TI  - Two novel rare variants of APOA5 gene found in subjects with severe
      hypertriglyceridemia.
AB  - BACKGROUND: Common variants of APOA5 gene affect plasma triglyceride (TG) in the
      population and a number of rare variants APOA5 have been reported in individuals
      with hypertriglyceridemia (HTG). METHODS: APOA5 was analysed in 98 HTG
      individuals (plasma TG >9 mmol/L) in whom no mutations in LPL and APOC2 had been
      found. RESULTS: Two patients were found to be heterozygous for two novel APOA5
      variants. The first variant (p.L253P) was identified in an obese male who
      consumed a diet rich in fat and simple sugars. He was also a carrier in trans of
      the common TG-raising p.S19W SNP (5*3 haplotype). The second variant (c.295-297
      del GAG, p.E99 del) was found in a lean male with no life style or metabolic
      factors known to affect plasma TG. He was a carrier in trans of the TG-raising
      5*2 haplotype and was homozygous for the rare c.1337T allele of a SNP of GCKR
      gene. No mutations in other genes affecting plasma TG (LMF1 and GPIHBP1) were
      found in these patients. These APOA5 variants, resulted to be deleterious in
      silico, were not found in 350 control subjects. CONCLUSIONS: These novel APOA5
      variants predispose to HTG in combination with other genetic or nutritional
      factors.

PMID- 21846465
TI  - Ub-family modifications at the replication fork: Regulating PCNA-interacting
      components.
AB  - A vast array of proteins is recruited to the replication fork in a dynamic and
      coordinated manner through physical interactions with Proliferating Cell Nuclear
      Antigen, PCNA. How this complex exchange of PCNA binding partners is
      choreographed to ensure proper replication origin licensing, DNA synthesis during
      normal replication or repair of DNA damage, chromatin assembly, DNA methylation,
      histone modification, and sister chromatid cohesion is only beginning to be
      appreciated. In this review, several roles of ubiquitin-related modifications in
      the recruitment and turnover of PCNA-interacting proteins at the replication fork
      are considered.

PMID- 21846467
TI  - A structural insight into the C-terminal RNA recognition motifs of T-cell
      intracellular antigen-1 protein.
AB  - T-cell intracellular antigen-1 (TIA-1) plays a pleiotropic role in cell
      homeostasis through the regulation of alternative pre-mRNA splicing and mRNA
      translation by recognising uridine-rich sequences of RNAs. TIA-1 contains three
      RNA recognition motifs (RRMs) and a glutamine-rich domain. Here, we characterise
      its C-terminal RRM2 and RRM3 domains. Notably, RRM3 contains an extra novel N
      terminal alpha-helix (alpha(1)) which protects its single tryptophan from the
      solvent exposure, even in the two-domain RRM23 context. The alpha(1) hardly
      affects the thermal stability of RRM3. On the contrary, RRM2 destabilises RRM3,
      indicating that both modules are tumbling together, which may influence the RNA
      binding activity of TIA-1.

PMID- 21846468
TI  - Ago1 and Ago2 differentially affect cell proliferation, motility and apoptosis
      when overexpressed in SH-SY5Y neuroblastoma cells.
AB  - Argonaute are a conserved class of proteins central to the microRNA pathway. We
      have highlighted a novel and non-redundant function of Ago1 versus Ago2; the two
      core factors of the miRNA-associated RISC complex. Stable overexpression of Ago1
      in neuroblastoma cells causes the cell cycle to slow down, a decrease in cellular
      motility and a stronger apoptotic response upon UV irradiation. These effects,
      together with a significant increase in p53 levels, suggest that Ago1 may act as
      a tumor-suppressor factor, a function also supported by GEO Profiles microarrays
      that inversely correlate Ago1 expression levels with cell proliferation rates.

PMID- 21846469
TI  - Functional expression of frog and rainbow trout melanocortin 2 receptors using
      heterologous MRAP1s.
AB  - Analysis of the functional expression of the melanocortin 2 receptor (MC2R) from
      a rather broad spectrum of vertebrates indicates that MC2R is exclusively
      selective for the ligand, ACTH, and the melanocortin receptor accessory protein 1
      (MRAP1) is required for high affinity ACTH binding and activation of MC2R. A
      phylogenetic analysis of MRAP1 suggested that tetrapod sequences and bony fish
      sequences may represent two distinct trends in the evolution of the mrap1 gene.
      To test this hypothesis, a frog (Xenopus tropicalis) MC2R was expressed in CHO
      cells either in the presence of a tetrapod (mouse) MRAP1 or a bony fish
      (zebrafish) MRAP1. The response of frog MC2R to different concentrations of human
      ACTH(1-24) was more robust in the presence of mouse MRAP1 than in the presence of
      zebrafish MRAP1. Conversely, the cAMP response mediated by the rainbow trout
      (Oncorhynchus mykiss) MC2R was almost twofold higher and occurred at 1000-fold
      lower ACTH concentration in the presence of zebrafish MRAP1 than in the presence
      of mouse MRAP1. Collectively, these experiments raise the possibility that at
      least two distinct trends have emerged in the co-evolution of MC2R/MRAP1
      interactions during the radiation of the vertebrates.

PMID- 21846470
TI  - Female goats use courtship display as an honest indicator of male quality.
AB  - Due to the differential cost of reproduction in promiscuous species, like
      domesticated goat(s) (Capra hircus), it is expected that females should mate with
      higher quality males, while males should mate with a greater number of females.
      Females may use conspicuous secondary sexual characteristics of males such as
      courtship display to distinguish among high and low quality males. Testosterone
      (T) controls a large suite of secondary sexual characteristics and variation in T
      concentrations may account of differences in courtship rates. Two studies were
      conducted to examine the relationship between T concentrations and courtship rate
      and its role in mammalian female mate choice. Experiment 1 utilized bucks (intact
      males) and Experiment 2 utilized T-replaced wethers (castrated pre-pubertally).
      During the first year of Experiment 2, T-replaced wethers received either vehicle
      control (CON), 25mg or 100mg testosterone propionate (TP). During the second year
      of Experiment 2, T-replaced wethers were treated with either 5mg, 15 mg or 25mg
      TP. For all experiments, mean courtship rates and circulating T concentrations
      were measured, as well as female preference for males displaying different
      courtship frequencies. T concentrations and courtship rate were positively
      correlated for bucks and estrous females preferred high courting bucks. Males
      receiving 25mg and 100mg TP courted females at a similar rate, but both were
      significantly higher than courtship rates of the CON wethers. Courtship rates of
      the 25mg, 15 mg and 5mg TP-treated males were all significantly different.
      Females did not show a preference between the 100mg or 25mg TP-treated wethers,
      however both were preferred in comparison to the CON wethers. Females did not
      show preference between the 25mg or 15 mg TP-treated wethers, however both were
      preferred in comparison to the 5mg TP-treated wethers. Taken together, these
      studies suggest that courtship rate is T-dependent. Further, females can use
      courtship rate to distinguish among males.

PMID- 21846466
TI  - Functional modulation of the metastatic suppressor Nm23-H1 by oncogenic viruses.
AB  - Evidence over the last two decades from a number of disciplines has solidified
      some fundamental concepts in metastasis, a major contributor to cancer associated
      deaths. However, significant advances have been made in controlling this critical
      cellular process by focusing on targeted therapy. A key set of factors associated
      with this invasive phenotype is the nm23 family of over twenty metastasis
      associated genes. Among the eight known isoforms, Nm23-H1 is the most studied
      potential anti-metastatic factor associated with human cancers. Importantly, a
      growing body of work has clearly suggested a critical role for Nm23-H1 in
      limiting tumor cell motility and progression induced by several tumor viruses,
      including Epstein-Barr virus (EBV), Kaposi's sarcoma associated herpes virus
      (KSHV) and human papilloma virus (HPV). A more in depth understanding of the
      interactions between tumor viruses encoded antigens and Nm23-H1 will facilitate
      the elucidation of underlying mechanism(s) which contribute to virus-associated
      cancers. Here, we review recent studies to explore the molecular links between
      human oncogenic viruses and progression of metastasis, in particular the
      deregulation of Nm23-H1 mediated suppression.

PMID- 21846471
TI  - Development of a panel of highly sensitive, equivalent assays for detection of
      antibody responses to velaglucerase alfa or imiglucerase enzyme replacement
      therapy in patients with Gaucher disease.
AB  - Anti-drug antibodies are elicited by virtually all therapeutic proteins, and
      standardized assays are required for clinical monitoring of patients as well as
      for comparing antibody response to different therapeutic proteins in clinical
      trials. Velaglucerase alfa and imiglucerase are enzyme replacement therapies for
      the long-term treatment of type 1 Gaucher disease, a lysosomal storage disease
      resulting from an inherited deficiency of the enzyme glucocerebrosidase. We used
      state-of-the-art tools to develop a panel of assays for detection and
      characterization of antibody responses to velaglucerase alfa and imiglucerase.
      Highly-sensitive, direct bridging electrochemiluminescence screening assays were
      developed using samples from treatment-naive individuals with type 1 Gaucher
      disease to set cut points. A mouse anti-glucocerebrosidase monoclonal antibody
      used as a calibrator was shown to have similar affinity and binding kinetics for
      anti-velaglucerase alfa and anti-imiglucerase antibodies. A quantitative
      radioimmunoprecipitation assay for IgG antibodies was developed to eliminate
      false-positives from the highly sensitive screening assay. Using 59 samples from
      treatment-naive individuals with type 1 Gaucher disease, the confirmatory cut
      points were calculated to be 1.42 ng/mL for anti-velaglucerase alfa antibodies
      and 3.23 ng/mL for anti-imiglucerase antibodies. Isotype-specific indirect
      electrochemiluminescence assays were developed for IgE, IgA, and IgM subclasses.
      The IgE subclass assay was shown to be more sensitive than the confirmatory assay
      using sheep anti-glucocerebrosidase polyclonal antibody cross-linked with
      fragments specific to human IgE, with cut points for anti-velaglucerase alfa or
      anti-imiglucerase antibodies determined to be 0.53 and 0.55 ng/mL, respectively.
      An assay that detects inhibition in vitro of velaglucerase alfa and imiglucerase
      hydrolysis of a synthetic substrate in the presence of antibodies was developed
      to test for neutralizing antibodies. Using 52 individual healthy human donor
      samples and 35 samples from treatment-naive individuals with type 1 Gaucher
      disease, cut points for the velaglucerase alfa and imiglucerase neutralizing
      antibody assays were determined to be 20%, such that a sample with greater than
      20% inhibition of enzyme activity in the presence of antibodies was considered
      positive for neutralizing antibodies. In conclusion, highly sensitive and
      equivalent methods were developed and validated to directly compare antibody
      response to velaglucerase alfa and imiglucerase treatments in patients with
      Gaucher disease, and may contribute to future internationally standardized assays
      for antibody detection in patients with Gaucher disease.

PMID- 21846472
TI  - Studies of the role of tubulin beta II isotype in regulation of mitochondrial
      respiration in intracellular energetic units in cardiac cells.
AB  - The aim of this study was to investigate the possible role of tubulin betaII, a
      cytoskeletal protein, in regulation of mitochondrial oxidative phosphorylation
      and energy fluxes in heart cells. This isotype of tubulin is closely associated
      with mitochondria and co-expressed with mitochondrial creatine kinase (MtCK). It
      can be rapidly removed by mild proteolytic treatment of permeabilized
      cardiomyocytes in the absence of stimulatory effect of cytochrome c, that
      demonstrating the intactness of the outer mitochondrial membrane. Contrary to
      isolated mitochondria, in permeabilized cardiomyocytes (in situ mitochondria) the
      addition of pyruvate kinase (PK) and phosphoenolpyruvate (PEP) in the presence of
      creatine had no effect on the rate of respiration controlled by activated MtCK,
      showing limited permeability of voltage-dependent anion channel (VDAC) in
      mitochondrial outer membrane (MOM) for ADP regenerated by MtCK. Under normal
      conditions, this effect can be considered as one of the most sensitive tests of
      the intactness of cardiomyocytes and controlled permeability of MOM for adenine
      nucleotides. However, proteolytic treatment of permeabilized cardiomyocytes with
      trypsin, by removing mitochondrial betaII tubulin, induces high sensitivity of
      MtCK-regulated respiration to PK-PEP, significantly changes its kinetics and the
      affinity to exogenous ADP. MtCK coupled to ATP synthasome and to VDAC controlled
      by tubulin betaII provides functional compartmentation of ATP in mitochondria and
      energy channeling into cytoplasm via phosphotransfer network. Therefore, direct
      transfer of mitochondrially produced ATP to sites of its utilization is largely
      avoided under physiological conditions, but may occur in pathology when
      mitochondria are damaged. This article is part of a Special Issue entitled
      ''Local Signaling in Myocytes''.

PMID- 21846473
TI  - Effects of exercise training and a hypocaloric diet on female monozygotic twins
      in free-living conditions.
AB  - This paper aims to examine the similarities in effects of exercise training and a
      hypocaloric diet within overweight female monozygotic twin pairs and to assess
      differences in twin partners' responses depending on the timing of exercise bouts
      and main meals. Six previously untrained twin pairs (aged 20-37 years, body fat
      35.8+/-6.3%) performed an identical exercise program (12 bouts endurance and 8
      bouts resistance training) and took part in a nutrition counseling program for a
      period of 28 days. They pursued one identical goal: to lose body weight and fat.
      Each twin partner was randomly assigned to one of the two intervention groups:
      "exercise after dinner" (A) and "exercise before dinner" (B). Subjects followed a
      hypocaloric diet, supervised by a nutritionist, in free-living conditions.
      Reductions in body weight, waist and hip circumference, glucose tolerance, mean
      daily %fat intake, changes in morning resting energy rate and resting metabolic
      rate showed great variation between twin pairs, but only small variation within
      twin pairs. Thus, the genetic influence on the changes in most of the examined
      anthropometric and physiological variables was high. There was no influence of
      the specific timing on the dependent variables.

PMID- 21846474
TI  - Phenylalanine 93 of the human UGT1A10 plays a major role in the interactions of
      the enzyme with estrogens.
AB  - Little is currently known about the substrate binding site of the human UDP
      glucuronosyltransferases (UGTs) and the structural elements that affect their
      complex substrate selectivity. In order to further understand and extend our
      earlier findings with phenylalanines 90 and 93 of UGT1A10, we have replaced each
      of them with Gly, Ala, Val, Leu, Ile or Tyr, and tested the activity of the
      resulting 12 mutants toward eight different substrates. Apart from scopoletin
      glucuronidation, the F90 mutants other than F90L were nearly inactive, while the
      F93 mutants' activity was strongly substrate dependent. Hence, F93L displayed
      high entacapone and 1-naphthol glucuronidation rates, whereas F93G, which was
      nearly inactive in entacapone glucuronidation, was highly active toward
      estradiol, estriol and even ethinylestradiol, a synthetic estrogen that is a poor
      substrate for the wild-type UGT1A10. Kinetic analyses of 4-nitrophenol, estradiol
      and ethinylestradiol glucuronidation by the mutants that catalyzed the respective
      reactions at considerable rates, revealed increased K(m) values for 4-nitrophenol
      and estradiol in all the mutants, whilst the K(m) values of F93G and F93A for
      ethinylestradiol were lower than in control UGT1A10. Based on the activity
      results and a new molecular model of UGT1A10, it is suggested that both F90 and
      F93 are located in a surface helix at the far end of the substrate binding site.
      Nevertheless, only F93 directly affects the selectivity of UGT1A10 toward large
      and rigid estrogens, particularly those with substitutions at the D ring. The
      effects of F93 mutations on the glucuronidation of smaller or less rigid
      substrates are indirect, however.

PMID- 21846475
TI  - Microwave assisted preparation of C1-C11 oxygen-bridged pregnanes.
AB  - 1,11-Epoxysteroids may be obtained by an intramolecular remote functionalization
      using Suarez reagent (diacetoxyiodobenzene/I(2)) and irradiation with visible
      light. We have found that photolysis with visible light may be advantageously
      replaced by microwave irradiation to prepare 1,11-oxygen bridges resulting in
      higher yields and shorter reaction times especially in the case of sensitive
      substrates. Both methodologies were compared on a set of representative 11-alpha
      hydroxypregnanes (3, 8, 10 and 11).

PMID- 21846476
TI  - Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic
      activation of PKCdelta in cell culture and animal models of Parkinson's disease.
AB  - The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular
      and molecular mechanisms underlying selective degeneration of dopaminergic
      neurons in Parkinson's disease (PD). Oxidative stress and caspase activation
      contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In
      the present study, we sought to systematically characterize the key downstream
      signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell
      culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal
      N27 cells with 6-OHDA (100 MUM) for 24h significantly reduced mitochondrial
      activity and increased cytosolic cytochrome c, followed by sequential activation
      of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP
      (10 MUM) significantly attenuated 6-OHDA-induced caspase activities.
      Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein
      kinase C delta (PKCdelta) was completely suppressed by treatment with a caspase-3
      specific inhibitor, Z-DEVD-FMK (50 MUM). Furthermore, expression of caspase-3
      cleavage site-resistant mutant PKCdelta(D327A) and kinase dead PKCdelta(K376R) or
      siRNA-mediated knockdown of PKCdelta protected against 6-OHDA-induced neuronal
      cell death, suggesting that caspase-3-dependent PKCdelta promotes oxidative
      stress-induced dopaminergic degeneration. Suppression of PKCdelta expression by
      siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell
      death. PKCdelta cleavage was also observed in the substantia nigra of 6-OHDA
      injected C57 black mice but not in control animals. Viral-mediated delivery of
      PKCdelta(D327A) protein protected against 6-OHDA-induced PKCdelta activation in
      mouse substantia nigra. Collectively, these results strongly suggest that
      proteolytic activation of PKCdelta is a key downstream event in dopaminergic
      degeneration, and these results may have important translational value for
      development of novel treatment strategies for PD.

PMID- 21846478
TI  - The effect of spatial orientation on detecting motion trajectories in noise.
AB  - A series of experiments investigated the extent to which the spatial orientation
      of a signal line affects discrimination of its trajectory from the random
      trajectories of background noise lines. The orientation of the signal line was
      either parallel (iso-) or orthogonal (ortho-) to its motion direction and it was
      identical in all respects to the noise (orientation, length and speed) except for
      its motion direction, rendering the signal line indistinguishable from the noise
      on a frame-to-frame basis. We found that discrimination of ortho-trajectories was
      generally better than iso-trajectories. Discrimination of ortho-trajectories was
      largely immune to the effects of spatial jitter in the trajectory, and to
      variations in step size and line-length. Discrimination of iso-trajectories was
      reliable provided that step-size was not too short and did not exceed line
      length, and that the trajectory was straight. The new result that trajectory
      discrimination in moving line elements is modulated by line orientation suggests
      that ortho- and iso-trajectory discrimination rely upon two distinct mechanisms:
      iso-motion discrimination involves a 'motion-streak' process that combines motion
      information with information about orientation parallel to the motion trajectory,
      while ortho-motion discrimination involves extended trajectory facilitation in a
      network of receptive fields with orthogonal orientation tuning.

PMID- 21846479
TI  - Mechanostasis in apoptosis and medicine.
AB  - Mechanostasis describes a complex and dynamic process where cells maintain
      equilibrium in response to mechanical forces. Normal physiological loading modes
      and magnitudes contribute to cell proliferation, tissue growth, differentiation
      and development. However, cell responses to abnormal forces include compensatory
      apoptotic mechanisms that may contribute to the development of tissue disease and
      pathological conditions. Mechanotransduction mechanisms tightly regulate the cell
      response through discrete signaling pathways. Here, we provide an overview of
      links between pro- and anti-apoptotic signaling and mechanotransduction signaling
      pathways, and identify potential clinical applications for treatments of disease
      by exploiting mechanically-linked apoptotic pathways.

PMID- 21846477
TI  - Nrf2 protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced
      oxidative injury and steatohepatitis.
AB  - Previous studies demonstrate that Nrf2, a master regulator of antioxidative
      responses, is essential in mediating induction of many antioxidative enzymes by
      acute activation of the AhR. However, the role of Nrf2 in protecting against
      oxidative stress and DNA damage induced by sustained activation of the AhR
      remains unknown and was investigated herein. Tissue and blood samples were
      collected from wild-type (WT) and Nrf2-null mice 21 days after administration of
      a low-toxic dose (10 MUg/kg ip) of TCDD. Only Nrf2-null mice lost body weight
      after TCDD treatment; however, blood levels of ALT were not markedly changed in
      either genotype, indicating a lack of extensive necrosis. Compared to livers of
      TCDD-treated WT mice, livers of TCDD-treated Nrf2-null mice had: 1) degenerated
      hepatocytes, lobular inflammation, marked fat accumulation, and higher mRNA
      expression of inflammatory and fibrotic genes; 2) depletion of glutathione,
      elevation in lipid peroxidation and marker of DNA damage; 3) attenuated induction
      of phase-II enzymes Nqo1, Gsta1/2, and Ugt2b35 mRNAs, but higher induction of
      cytoprotective Ho-1, Prdx1, Trxr1, Gclc, and Epxh1 mRNAs; 4) higher mRNA
      expression of Fgf21 and triglyceride-synthesis genes, but down-regulation of bile
      acid-synthesis genes and cholesterol-efflux transporters; and 5) trend of
      induction/activation of c-jun and NF-kB. Additionally, TCDD-treated Nrf2-null
      mice had impaired adipogenesis in white adipose tissue. In conclusion, Nrf2
      protects livers of mice against oxidative stress, DNA damage, and steatohepatitis
      induced by TCDD-mediated sustained activation of the AhR. The aggravated
      hepatosteatosis in TCDD-treated Nrf2-null mice is due to increased lipogenesis in
      liver and impaired lipogenesis in white adipose tissue.

PMID- 21846480
TI  - Associations between regional socioeconomic deprivation and cancer risk: Analysis
      of population-based Cancer Registry data from Bavaria, Germany.
AB  - OBJECTIVE: Previous research from other countries shows a positive association
      between cancer risk and regional deprivation. This study explores this
      association for lung and colorectal cancers in Germany. METHOD: Regional
      deprivation was assessed by the 'Bavarian Index of Multiple Deprivation'. Cancer
      data were provided by the Cancer Registry of Bavaria (2003-2006). The association
      between cancer risk and regional deprivation was evaluated by multilevel Poisson
      regression analysis. RESULTS: Crude incidence and mortality rates (per 1000
      people) in the least deprived areas were 1.46 and 0.92 for lung cancer, 2.82 and
      0.69 for colorectal cancer. For lung cancer, the age-adjusted relative risk (RR)
      for incidence in the most deprived districts (compared with the least deprived)
      in men was 1.41 (95% CI: 1.28-1.54), for mortality 1.59 (95% CI: 1.40-1.80); in
      women, an elevated RR was seen for mortality (1.24, 95% CI: 1.06-1.46). For
      colorectal cancer, the RR for incidence (men: 1.31, 95% CI: 1.17-1.46; women:
      1.25, 95% CI: 1.12-1.40) and mortality (men: 1.51, 95% CI: 1.28-1.80; women:
      1.49, 95% CI: 1.26-1.77) was always highest in the most deprived districts.
      CONCLUSION: At the district level in Bavaria, the risk for lung and colorectal
      cancers mostly increases with increasing regional deprivation.

PMID- 21846481
TI  - The clinical implication and prognostic predictors of tigecycline treatment for
      pneumonia involving multidrug-resistant Acinetobacter baumannii.
AB  - OBJECTIVES: To investigate the clinical implication and prognostic predictors of
      tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter
      baumannii (MDRAB). METHODS: A retrospective observational study over a 32-month
      period for adult patients receiving tigecycline treatment at least 7 days for
      pneumonia involving MDRAB. RESULTS: We reviewed 112 patients with 116 episodes of
      tigecycline-treated pneumonia involving MDRAB. The mean age was 70.8 years. The
      mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.7.
      Seventy episodes (60.3%) had clinical resolution. The episodes with monomicrobial
      MDRAB pneumonia had a significantly lower clinical resolution rate than
      polymicrobial pneumonia (14/31, 45.2% vs. 56/85, 65.9%; p = 0.044). The
      independent predictors for failure of clinical resolution were female gender,
      malignancy, bilateral pneumonia, monomicrobial pneumonia, and higher APHCHE II
      scores. Forty-two episodes (36.2%) had the 30-day mortality, and the only
      independent predictor was deterioration of pneumonia on chest radiographs.
      CONCLUSIONS: A high disease severity, bilateral pneumonia, and monomicrobial
      MDRAB pneumonia predicted failure of clinical resolution, and deterioration of
      pneumonia predicted mortality. MDRAB in monomicrobial pneumonia was the most
      certain to be causal. The clinical resolution rate from such pneumonia might
      reflect the ultimate efficacy of tigecycline in treating MDRAB pneumonia and the
      overall efficacy might be overestimated.

PMID- 21846482
TI  - The feedback-related negativity is modulated by feedback probability in
      observational learning.
AB  - The feedback-related negativity (FRN), an event-related potentials (ERPs)
      component reflecting activity of the anterior cingulate cortex (ACC), has been
      shown to be modulated by feedback expectancy following active choices in feedback
      based learning tasks. A general reduction of FRN amplitude has been described in
      observational feedback learning, raising the question whether FRN amplitude is
      modulated in a similar way in this type of learning. The present study
      investigated whether the FRN and the P300 - a second ERP component related to
      feedback processing - are modulated by feedback probability in observational
      learning. Thirty-two subjects participated in the experiment. They observed a
      virtual person choosing between two symbols and receiving positive or negative
      feedback. Learning about stimulus-specific feedback probabilities was assessed in
      active test trials without feedback. In addition, the bias to learn from positive
      or negative feedback and - in a subsample of 17 subjects - empathy scores were
      obtained. General FRN and P300 modulations by feedback probability were found
      across all subjects. Only for the FRN in learners, an interaction between
      probability and valence was observed. Larger FRN amplitudes for negative relative
      to positive feedback only emerged for the lowest outcome probability. The results
      show that feedback expectancy modulates FRN amplitude also in observational
      learning, suggesting a similar ACC function as in active learning. On the other
      hand, the modulation is only seen for very low feedback expectancy, which
      suggests that brain regions other than those of the reward system contribute to
      feedback processing in an observation setting.

PMID- 21846484
TI  - Nuclear drug delivery for cancer chemotherapy.
AB  - Nanosystems with unique physical and biological properties have been extensively
      explored for cancer targeted intracellular delivery of small-molecular
      chemotherapeutic drugs to increase their therapeutic efficacies and to minimize
      their side effects. A large number of anticancer drugs are DNA-toxins that bind
      nuclear DNA or its associated enzymes to exert their cytotoxicity to cancer
      cells. After entering tumor cells, they need to be further delivered to the
      nucleus for actions. Herein, we discuss the biological barriers and summarize
      recent progress of nuclear drug delivery for cancer chemotherapy, emphasizing
      strategies that appear useful for design of vehicles capable of delivering drugs
      to the nucleus, particularly for in vivo applications. The existing obstacles or
      problems that need to be overcome before successful applications of nuclear drug
      delivery for cancer chemotherapy are also discussed.

PMID- 21846483
TI  - Thermo-targeted drug delivery of geldanamycin to hyperthermic tumor margins with
      diblock elastin-based biopolymers.
AB  - The tumor margins are the barrier to hepatocellular carcinoma (HCC) eradication
      for tumors>3 cm. Indeed, inadequately treated tumor margins commonly result in
      local and regional HCC recurrence with increased size and mass. Tumor recurrence
      is a common problem with chemotherapy, radiotherapy, thermal ablation, and/or
      surgical resection, by the inability to properly treat the tumor core and the
      tumor margins. Here we present novel thermosensitive biopolymer-drug conjugates
      for thermo-targeted chemotherapy at hyperthermic isotherms produced by focal,
      locoregional thermal ablation. The chemotherapeutic target is heat shock protein
      90 (HSP90), a key molecular chaperone of several, and potent pro-oncogenic
      pathways including Akt, Raf-1, and mutated p53 that is upregulated in HCC. To
      inhibit HSP90, we have chosen geldanamycin (GA), a potent HSP90 inhibitor. GA has
      gained significant attention for its low IC50 ~ 1 nM and inhibition of Akt and
      Raf-1, amongst other critical pro-oncogenic pathways. Despite such evidence,
      clinical trials of GA have not shown promise due to off-target toxicity and poor
      formulation design. Here, we propose using diblock elastin-based biopolymers as a
      Ringsdorf macromolecular GA solubilizer--a new generation containing functional
      poly(Asp)/(Glu) blocks for facile drug conjugation and an ELP block for thermo
      targeting of hyperthermic ablative margins. GA release is controlled by pH
      sensitive, covalent hydrazone bonds with the biopolymer backbone to avoid
      systemic toxicity and off-target effects. The resultant biopolymer-conjugates
      form stable nanoconstructs and display tunable, acute phase transitions at high
      temperatures. Drug release kinetics are favorable with or without the presence of
      serum. Thermo-targeted chemotherapy and synchronous thermal ablation provide a
      unique opportunity for simultaneous destruction of the HCC ablative margins and
      tumor core for focal, locoregional control of HCC.

PMID- 21846485
TI  - Delivery of a multivalent scrambled antigen vaccine induces broad spectrum
      immunity and protection against tuberculosis.
AB  - The development of effective anti-Tuberculosis (TB) vaccines is an important step
      towards improved control of TB in high burden countries. Subunit vaccines are
      advantageous in terms of safety, particularly in the context of high rates of HIV
      co-infection, but they must contain sufficient Mycobacterium tuberculosis
      antigens to stimulate immunity in genetically diverse human populations. We have
      used a novel approach to develop a synthetic scrambled antigen vaccine (TB
      SAVINE), comprised of overlapping, recombined peptides from four M. tuberculosis
      proteins, Ag85B, ESAT-6, PstS3 and Mpt83, each of which is immunogenic and
      protective against experimental TB. This polyvalent TB-SAVINE construct
      stimulated CD4 and CD8T cell responses against the individual proteins and M.
      tuberculosis in C57BL/6 and Balb/c mice, when delivered as DNA, Fowl Pox Virus or
      Vaccinia Virus vaccines. In addition, the DNA-TBS vaccine induced protective
      immunity against pulmonary M. tuberculosis infection in C57BL/6 mice. Co
      immunization of Balb/c mice with virally expressed TBS and HIV1-SAVINE vaccine
      stimulated strong T cell responses to both the M. tuberculosis and HIV proteins,
      indicating no effects of antigenic competition. Further development of this TB
      SAVINE vaccine expressing components from multiple M. tuberculosis proteins may
      prove an effective vaccine candidate against TB, which could potentially form
      part of a safe, combined preventative strategy together with HIV immunisations.

PMID- 21846486
TI  - Mitochondrial calcium handling during ischemia-induced cell death in neurons.
AB  - Mitochondria sense and shape cytosolic Ca(2+) signals by taking up and
      subsequently releasing Ca(2+) ions during physiological and pathological Ca(2+)
      elevations. Sustained elevations in the mitochondrial matrix Ca(2+) concentration
      are increasingly recognized as a defining feature of the intracellular cascade of
      lethal events that occur in neurons during cerebral ischemia. Here, we review the
      recently identified transport proteins that mediate the fluxes of Ca(2+) across
      mitochondria and discuss the implication of the permeability transition pore in
      decoding the abnormally sustained mitochondrial Ca(2+) elevations that occur
      during cerebral ischemia.

PMID- 21846487
TI  - Neural activation during the processing of ambiguous fearful facial expressions:
      an ERP study in anxious and nonanxious individuals.
AB  - Event-related brain potentials (ERPs) were recorded from anxious and nonanxious
      participants during performance on a fear detection task. Sequential presentation
      of gradually increasing fear cues from neutral to fearful allowed an examination
      of anxiety-related differences in the neural activation patterns corresponding to
      participants' overt detection of fear in ambiguous stimuli as well as the
      activation patterns corresponding to stages of fear processing preceding overt
      fear detection. While centro-parietal Late Positive Potential (LPP) amplitude of
      nonanxious participants was significantly modulated by increases in stimulus fear
      intensity preceding overt fear detection, no such LPP sensitivity was detected in
      anxious participants. Additionally, anxiety group differences as well as emotion
      related modulation were found for earlier ERP components (P1, P2 and EPN). These
      findings reveal an anxiety-related dissociation between the early and late
      processing stages of threat processing. Implications are discussed in light of
      existing theories of cognitive biases in anxiety.

PMID- 21846489
TI  - Enzymatic removal of polysialic acid from neural cell adhesion molecule
      interrupts gonadotropin releasing hormone (GnRH) neuron-glial remodeling.
AB  - There is abundant evidence to prove that the astrocytes are highly dynamic cell
      type in CNS and under physiological conditions such as reproduction, these cells
      display a remarkable structural plasticity especially at the level of their
      distal processes ensheathing the gonadotropin releasing hormone (GnRH) axon
      terminals. The morphology of GnRH axon terminals and astrocytes in the median
      eminence region of hypothalamus show activity dependent structural plasticity
      during different phases of estrous cycle. In the current study, we have assessed
      the functional contribution of infinity-2,8-linked polysialic acid (PSA) on
      neural cell adhesion molecule (PSA-NCAM) in this neuronal-glial plasticity using
      both in vitro and in vivo model systems. In vivo experiments were carried out
      after stereotaxic injection of endoneuraminidase enzyme (endo-N) near median
      eminence region of hypothalamus to specifically remove PSA residues on NCAM
      followed by localization of GnRH, PSA-NCAM and glial fibrillary acidic protein
      (GFAP) by immunostaining. Using in vitro model, structural remodeling of GnV-3
      cells, (a conditionally immortalized GnRH cell line) co-cultured with primary
      astrocytes was studied after treating the cells with endo-N. Marked morphological
      changes were observed in GnRH axon terminals in proestrous phase rats and control
      GnV-3 cells as compared to endo-N treatment i.e. after removal of PSA. The
      specificity of endo-N treatment was also confirmed by studying the expression of
      PSA-NCAM by Western blotting in cultures treated with and without endo-N. Removal
      of PSA from surfaces with endo-N prevented stimulation associated remodeling of
      GnRH axon terminals as well as their associated glial cells under both in vivo
      and in vitro conditions. The current data confirms the permissive role of PSA to
      promote dynamic remodeling of GnRH axon terminals and their associated glia
      during reproductive cycle in rats.

PMID- 21846490
TI  - Concentration of activin A and follistatin in follicular fluid from human small
      antral follicles associated to gene expression of the corresponding granulosa
      cells.
AB  - The present study correlated concentrations of activin A and follistatin in
      follicular fluid (FF) from human small antral follicles to FF concentrations of
      AMH, inhibin B, progesterone, and oestradiol and to the mRNA expression of FSH
      receptor (FSHR), LH-receptor (LHR), AMH-receptor2 (AMHR2), CYP19a, and androgen
      receptor (AR) in the corresponding granulosa cells (GC). FF from 144 follicles (3
      12 mm in diameter) was included whereas mRNA expression profiles were established
      in GC from 66 of the 144 follicles. Levels of follistatin remained constant in
      relation to follicular diameter, whereas activin A levels increased in follicles
      exceeding 10 mm in diameter. Levels of activin A and inhibin B showed a highly
      significant inverse association. Follistatin showed highly significant positive
      associations with AMH and inhibin B levels and with FSHR and AR gene expression
      in GC. This study revealed unexpected associations that probably reflect the
      complicated regulatory mechanisms governing human folliculogenesis.

PMID- 21846488
TI  - Interaction between gonadotropin-releasing hormone and bone morphogenetic protein
      6 and -7 signaling in LbetaT2 gonadotrope cells.
AB  - It is known that bone morphogenetic proteins (BMPs) regulate gonadotropin
      transcription and production by pituitary gonadotrope cells. However, the role of
      BMPs in gonadotropin-releasing hormone (GnRH)-induced FSH production remains
      uncertain. Here, we describe a functional link between BMP-6 and BMP-7 signals
      and FSH transcriptional activity induced by GnRH using mouse gonadotrope LbetaT2
      cells. In LbetaT2 cells, BMP-6 and BMP-7 increased mouse FSHbeta-promoter
      activity in a concentration-dependent manner. The induction by BMP-6 and BMP-7
      was inhibited by treatment with extracellular domains of ActRII but not BMPRII.
      These findings suggest that the type II receptor ActRII participates in BMP
      induced FSHbeta transcription regulation. Notably, BMP-6, but not BMP-7, enhanced
      GnRH-induced FSHbeta-promoter activity in LbetaT2 cells. Since GnRH stimulated
      MAPK phosphorylation in LbetaT2 cells, a functional link between MAPK and FSHbeta
      transcription was examined. Inhibition of the ERK pathway, but not that of p38 or
      SAPK/JNK signaling, suppressed GnRH-induced FSHbeta transcription, suggesting
      that ERK is functionally involved in GnRH-induced FSHbeta transcription. Co
      treatment with BMP-7, but not with BMP-6, suppressed GnRH-induced MAPK
      phosphorylation in LbetaT2 cells. Thus, the difference between BMP-6 and BMP-7 in
      enhancing GnRH-induced FSHbeta transcription may be due to the differential
      effects of BMP ligands on GnRH-induced ERK signaling. On the other hand, GnRH
      reduced Smad1/5/8 phosphorylation but increased Smad6/7 expression. These
      findings imply the presence of a functional link between GnRH action, MAPK
      signaling and the BMP system in pituitary gonadotropes for fine-tuning of FSH
      gene expression.

PMID- 21846491
TI  - Mitochondria and autophagy: critical interplay between the two homeostats.
AB  - BACKGROUND: Mitochondria are dynamic organelles that frequently change their
      number, size, shape, and distribution in response to intra- and extracellular
      cues. After proliferated from pre-existing ones, fresh mitochondria enter
      constant cycles of fission and fusion that organize them into two distinct states
      - "individual state" and "network state". When compromised with various injuries,
      solitary mitochondria are subjected to organelle degradation. This clearance
      pathway relies on autophagy, a self-eating process that plays key roles in
      manifold cell activities. Recent studies reveal that defects in autophagic
      degradation selective for mitochondria (mitophagy) are associated with
      neurodegenerative diseases, highlighting the physiological relevance to cellular
      functions. SCOPE OF REVIEW: Here we review recent progress regarding a link
      between mitochondria and autophagy in yeast and multicellular eukaryotes. In
      particular, fundamental principles underlying mitophagy, and mitochondrial
      quality control are emphasized. Accumulating evidence also implicates
      nonselective autophagy in the management of mitochondrial fitness. Conversely,
      mitochondria are suggested to serve as signaling platforms vital for regulating
      autophagy. These interdependent relationships are likely to coordinate metabolic
      plasticity in the cell. MAJOR CONCLUSIONS: Mitochondria and autophagy are
      elaborately linked homeostatic elements that act in response to changes in
      cellular environment such as energy, nutrient, and stress. How cells integrate
      these double membrane-bound systems still remains elusive. GENERAL SIGNIFICANCE:
      Interplay between mitochondria and autophagy seems to be evolutionarily
      conserved. Defects in one of these elements could simultaneously impair the
      other, resulting in risk increments for various human diseases. This article is
      part of a Special Issue entitled Biochemistry of Mitochondria.

PMID- 21846492
TI  - Anion binding properties of the transferrins. Implications for function.
AB  - BACKGROUND: Since the transferrins have been defined by the highly cooperative
      binding of Fe(3+) and a carbonate anion to form an Fe-CO(3)-Tf ternary complex,
      the focus has been on synergistic anion binding. However, there are other types
      of anion binding with both apotransferrin and diferric transferrin that affect
      metal binding and release. SCOPE OF REVIEW: This review covers the binding of
      anions to the apoprotein, as well as the formation and structure of Fe-anion
      transferrin ternary complexes. It also covers interactions between ferric
      transferrin and non-synergistic anions that appear to be important in vivo.
      GENERAL SIGNIFICANCE: The interaction of anions with apotransferrin can alter the
      effective metal binding constants, which can affect the transport of metal ions
      in serum. These interactions also play a role in iron release under physiological
      conditions. MAJOR CONCLUSIONS: Apotransferrin binds a variety of anions with no
      special selectivity for carbonate. The selectivity for carbonate as a synergistic
      anion is associated with the iron binding reaction. Conformational changes in the
      binding of the synergistic carbonate and competition from non-synergistic anions
      both play a role in intracellular iron release. Anion competition also occurs in
      serum and reduces the effective metal binding affinity of Tf. Lastly, anions bind
      to allosteric sites (KISAB sites) on diferric transferrin and alter the rates of
      iron release. The KISAB sites have not been well-characterized, but kinetic
      studies on iron release from mutant transferrins indicate that there are likely
      to be multiple KISAB sites for each lobe of transferrin. This article is part of
      a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and
      disorders.

PMID- 21846493
TI  - Human prosaccades and antisaccades under risk: effects of penalties and rewards
      on visual selection and the value of actions.
AB  - Monkey studies report greater activity in the lateral intraparietal area and more
      efficient saccades when targets coincide with the location of prior reward cues,
      even when cue location does not indicate which responses will be rewarded. This
      suggests that reward can modulate spatial attention and visual selection
      independent of the "action value" of the motor response. Our goal was first to
      determine whether reward modulated visual selection similarly in humans, and
      next, to discover whether reward and penalty differed in effect, if cue effects
      were greater for cognitively demanding antisaccades, and if financial
      consequences that were contingent on stimulus location had spatially selective
      effects. We found that motivational cues reduced all latencies, more for reward
      than penalty. There was an "inhibition-of-return"-like effect at the location of
      the cue, but unlike the results in monkeys, cue valence did not modify this
      effect in prosaccades, and the inhibition-of-return effect was slightly increased
      rather than decreased in antisaccades. When financial consequences were
      contingent on target location, locations without reward or penalty consequences
      lost the benefits seen in noncontingent trials, whereas locations with
      consequences maintained their gains. We conclude that unlike monkeys, humans show
      reward effects not on visual selection but on the value of actions. The human
      saccadic system has both the capacity to enhance responses to multiple locations
      simultaneously, and the flexibility to focus motivational enhancement only on
      locations with financial consequences. Reward is more effective than penalty, and
      both interact with the additional attentional demands of the antisaccade task.

PMID- 21846494
TI  - Protective effects of valproic acid on the nigrostriatal dopamine system in a 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
AB  - The use of animal models (including the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine [MPTP] mouse model) to mimic dopaminergic (DAergic) cell loss
      and striatal dopamine (DA) depletion, as seen in Parkinson's disease (PD), has
      implicated a multitude of factors that might be associated with DAergic cell
      death in PD including excitotoxicity, inflammation, and oxidative stress. All of
      these factors have been shown to be reduced by administration of histone
      deacetylase (HDAC) inhibitors (HDACis) resulting in some degree of
      neuroprotection in various models of neurodegenerative disease including in
      Huntington's disease and amyotrophic lateral sclerosis. However, there is limited
      information of effects of HDACis in PD models. We have previously shown HDACis to
      be partially protective against 1-methyl-4-phenylpyridinium (MPP(+))-mediated
      cell loss in vitro. The present study was conducted to extend these findings to
      an in vivo PD model. The HDACi valproic acid (VPA) was co-administered with MPTP
      for 5 days to male FVBn mice and continued for an additional 2 weeks, throughout
      the period of active neurodegeneration associated with MPTP-mediated DAergic cell
      loss. VPA was able to partially prevent striatal dopamine depletion and almost
      completely protect against substantia nigra DAergic cell loss. These results
      suggest that VPA may be a potential disease-modifying therapy for PD.

PMID- 21846495
TI  - Telencephalic organization of the olfactory system in homing pigeons (Columba
      livia).
AB  - Pigeons use olfactory cues to navigate over unfamiliar areas, and any impairment
      of the olfactory system generates remarkable reduction of homing performance.
      Lesion and deprivation studies suggest a critical involvement of the right
      nostril and thus, the right olfactory bulb (OB) and the left piriform cortex
      (CPi) for initial orientation. This functional pattern suggests that OB and CPi
      are asymmetrically connected with a stronger projection from the right OB to the
      left CPi. However, the structural organization of the olfactory system is not
      unequivocally clarified yet. Thus, we re-analyzed the system by antero- and
      retrograde tract tracing with biotinylated dextran amine and choleratoxin subunit
      B, and we especially evaluated quantitative differences in the number of cells in
      the OB innervating the left and right CPi. Our anterograde tracing data verified
      a strong bilateral input to the CPi, and the prepiriform cortex (CPP), as well as
      small projections to the ipsilateral medial septum and the dorsolateral corticoid
      area and the nucleus taeniae of the amygdala in both hemispheres. Apart from the
      bilateral bulbar afferents, CPi in turn receives unequivocal input from the
      ipsilateral CPP, hyperpallium densocellulare, dorsal arcopallium, and from a
      cluster of cells located within the frontolateral nidopallium. Thus, an indirect
      connection between OB and CPi is only mediated by the CPP. For quantitative
      analysis of bulbar input to the CPi, we counted the number of ipsi- and
      contralaterally projecting neurons located in the OB after injections into the
      left or right CPi. Retrogradely labeled cells were found bilaterally in the OB
      with a higher number of ipsilaterally located cells. The bilaterality index did
      not differ after left- or right-sided CPi injections indicating that the
      functional lateralization of the olfactory system is not simply based on
      differences in the number of projecting axons of the major processing stream.

PMID- 21846496
TI  - Modulation of the activity of globus pallidus by dopamine D1-like receptors in
      parkinsonian rats.
AB  - Morphological studies have shown that the globus pallidus receives dopaminergic
      innervation from the collaterals of nigrostriatal fibers. Dopamine D1-like
      receptors are expressed at both pre- and postsynaptic membrane. In the present
      study, we investigate the in vivo electrophysiological and behavioral effects of
      pallidal dopamine D1-like receptors in parkinsonian rats. On the lesioned side of
      6-hydroxydopamine (6-OHDA) parkinsonian rats, micropressure ejection of dopamine
      D1-like receptor agonist, SKF38393, increased (88.2 +/- 18.6%) the firing rate in
      10 out of the 32 pallidal neurons, but decreased (49.5 +/- 6.1%) the firing rate
      in 14 out of the 32 neurons. Furthermore, on the unlesioned side of parkinsonian
      rats, SKF38393 increased (43.0 +/- 6.3%) the firing rate in 9 out of the 30
      pallidal neurons, but decreased (47.1 +/- 4.8%) the firing rate in 13 out of the
      30 neurons. In behaving rats, unilateral microinjection of SKF38393 led to
      contralateral deflection in the presence of systemic haloperidol administration.
      The selective dopamine D1-like receptor antagonist, SCH23390, blocked both
      SKF38393-induced electrophysiological and behavioral effects. Combining
      electrophysiological and behavioral findings, we concluded that activation of
      dopamine D1-like receptors modulates the activity of globus pallidus neurons in
      rats.

PMID- 21846497
TI  - Association of A-FABP gene polymorphism in intron 1 with meat quality traits in
      Junmu No. 1 white swine.
AB  - This study was designed to investigate the single nucleotide polymorphism (SNP)
      in intron 1 of the gene A-FABP in 127 Junmu No. 1 white swine using PCR-SSCP. The
      association between the polymorphism and meat quality traits was also studied.
      The cloning and sequencing results indicated that the polymorphism of intron 1
      was due to a point mutation in position 3481bp of A-FABP, giving 3 genotypes (CC,
      CD and DD). Association analysis indicated that the polymorphism had a
      significant effect on marbling (P<0.05). Genotype DD had higher marbling than CD
      and CC, but the difference between CD and CC was no significant. Polymorphism had
      a highly significant effect on intramuscular fat (IMF) content (P<0.01). DD was
      higher than CD, which was higher than CC. No significant conclusions can be drawn
      regarding other traits. Immunoblot analysis of A-FABP levels was carried out on 3
      different genotype individuals. Expression was markedly reduced in DD compared
      with genotype CC. Thus A-FABP may be a candidate gene or a quantitative trait
      locus-linked gene associated with meat quality traits.

PMID- 21846499
TI  - Bioreactor systems for in vitro production of foreign proteins using plant cell
      cultures.
AB  - Plant cells have been demonstrated to be an attractive heterologous expression
      host (using whole plants and in vitro plant cell cultures) for foreign protein
      production in the past 20years. In recent years in vitro liquid cultures of plant
      cells in a fully contained bioreactor have become promising alternatives to
      traditional microbial fermentation and mammalian cell cultures as a foreign
      protein expression platform, due to the unique features of plant cells as a
      production host including product safety, cost-effective biomanufacturing, and
      the capacity for complex protein post-translational modifications. Heterologous
      proteins such as therapeutics, antibodies, vaccines and enzymes for
      pharmaceutical and industrial applications have been successfully expressed in
      plant cell culture-based bioreactor systems including suspended dedifferentiated
      plant cells, moss, and hairy roots, etc. In this article, the current status and
      emerging trends of plant cell culture for in vitro production of foreign proteins
      will be discussed with emphasis on the technological progress that has been made
      in plant cell culture bioreactor systems.

PMID- 21846500
TI  - Biotechnological routes based on lactic acid production from biomass.
AB  - Lactic acid, the most important hydroxycarboxylic acid, is now commercially
      produced by the fermentation of sugars present in biomass. In addition to its use
      in the synthesis of biodegradable polymers, lactic acid can be regarded as a
      feedstock for the green chemistry of the future. Different potentially useful
      chemicals such as pyruvic acid, acrylic acid, 1,2-propanediol, and lactate ester
      can be produced from lactic acid via chemical and biotechnological routes. Here,
      we reviewed the current status of the production of potentially valuable
      chemicals from lactic acid via biotechnological routes. Although some of the
      reactions described in this review article are still not applicable at current
      stage, due to their "greener" properties, biotechnological processes for the
      production of lactic acid derivatives might replace the chemical routes in the
      future.

PMID- 21846498
TI  - Adenosine kinase inhibition in the cochlea delays the onset of age-related
      hearing loss.
AB  - This study was undertaken to determine the role of adenosine signalling in the
      development of age-related hearing loss (ARHL). We and others have shown
      previously that adenosine signalling via A(1) receptors is involved in cochlear
      protection from noise-induced cochlear injury. Here we demonstrate that enhanced
      adenosine signalling in the cochlea provides partial protection from ARHL in
      C57BL/6J mice. We targeted adenosine kinase (ADK), the key enzyme in adenosine
      metabolism, using a treatment regime with the selective ADK inhibitor ABT-702
      (1.5mg/kg intraperitoneally twice a week) commencing at the age of three months
      or six months. This treatment, intended to increase free adenosine levels in the
      cochlea, was maintained until the age of nine months and hearing thresholds were
      evaluated monthly using auditory brainstem responses (ABR). At nine months, when
      C57BL/6J mice normally exhibit significant ARHL, both groups treated with ABT-702
      showed lower ABR threshold shifts at 10 and 16kHz compared to control animals
      receiving the vehicle solution. The better thresholds of the ABT-702-treated mice
      at these frequencies were supported by increased survival of hair cells in the
      apical region of the cochlea. This study provides the first evidence that ARHL
      can be mitigated by enhancing adenosine signalling in the cochlea.

PMID- 21846501
TI  - Fifteen years of large scale metabolic modeling of yeast: developments and
      impacts.
AB  - Since the first large-scale reconstruction of the Saccharomyces cerevisiae
      metabolic network 15 years ago the development of yeast metabolic models has
      progressed rapidly, resulting in no less than nine different yeast genome-scale
      metabolic models. Here we review the historical development of large-scale
      mathematical modeling of yeast metabolism and the growing scope and impact of
      applications of these models in four different areas: as guide for metabolic
      engineering and strain improvement, as a tool for biological interpretation and
      discovery, applications of novel computational framework and for evolutionary
      studies.

PMID- 21846502
TI  - Enhancement of griseofulvin release from liquisolid compacts.
AB  - The potential of hydrophilic aerogel formulations and liquisolid systems to
      improve the release of poorly soluble drugs was investigated using griseofulvin
      as model drug. The in vitro release rates of this drug formulated as directly
      compressed tablets containing crystalline griseofulvin were compared to aerogel
      tablets with the drug adsorbed onto hydrophilic silica aerogel and to liquisolid
      compacts containing the drug dissolved or suspended in PEG 300. Furthermore, the
      commonly used carrier and coating materials in liquisolid systems Avicel(r) and
      Aerosil(r) were replaced by Neusilin(r), an amorphous magnesium
      aluminometasilicate with an extremely high specific surface area of 339 m2/g to
      improve the liquisolid approach. Both the liquisolid compacts containing the drug
      dissolved in PEG 300 and the aerogel tablets showed a considerably faster drug
      release than the directly compressed tablets. With liquisolid compacts containing
      the drug suspended in PEG 300, the release rate increased with rising fraction of
      dissolved drug in the liquid portion. It could be shown that Neusilin(r) with its
      sevenfold higher liquid adsorption capacity than the commonly used Avicel(r) and
      Aerosil(r) allows the production of liquisolid formulations with lower tablet
      weights.

PMID- 21846503
TI  - Characterization of a novel molluscan MyD88 family protein from manila clam,
      Ruditapes philippinarum.
AB  - Myeloid differentiation factor 88 (MyD88) is a universal adaptor protein which is
      required for signal transduction of TLR/IL-1R family. In this study, a novel
      molluscan MyD88 family member protein (named as RpMyD88) was identified from
      manila clam, Ruditapes philippinarum. It was identified using BLAST algorithm
      from GS-FLXTM sequencing data. The cDNA of RpMyD88 consists of 1416 bp open
      reading frame (ORF) encoding 471 amino acid residues. The RpMyD88 contains death
      domain and Toll/interleukin-1 receptor (TIR) domain which are typical features of
      MyD88 family proteins. The predicted amino acid sequence of RpMyD88 shares 27%
      identity with scallop MyD88. The expression level of RpMyD88 mRNA was
      investigated in healthy and challenged clams by quantitative real-time RT-PCR.
      The RpMyD88 gene expression is ubiquitous in all selected tissues. The RpMyD88
      mRNA was strongly expressed in hemocyte, gill and mantle. In contrast, it was
      weakly expressed in siphon, foot and adductor muscle. RpMyD88 was up-regulated in
      gill and hemocyte after immune challenge with both Vibrio tapetis and LPS
      challenge. All results considered, sequence characterization, comparison and gene
      expression data suggesting that MyD88-dependent signaling pathway is presence in
      manila clam and RpMyD88 plays an important role in innate immune response against
      bacteria.

PMID- 21846504
TI  - Alteration of brain default network in subacute phase of injury in concussed
      individuals: resting-state fMRI study.
AB  - There are a number of symptoms, both neurological and behavioral, associated with
      a single episode of r mild traumatic brain injury (mTBI). Neuropsychological
      testing and conventional neuroimaging techniques are not sufficiently sensitive
      to detect these changes, which adds to the complexity and difficulty in relating
      symptoms from mTBI to their underlying structural or functional deficits. With
      the inability of traditional brain imaging techniques to properly assess the
      severity of brain damage induced by mTBI, there is hope that more advanced
      neuroimaging applications will be more sensitive, as well as specific, in
      accurately assessing mTBI. In this study, we used resting state functional
      magnetic resonance imaging to evaluate the default mode network (DMN) in the
      subacute phase of mTBI. Fourteen concussed student-athletes who were asymptomatic
      based upon clinical symptoms resolution and clearance for aerobic exercise by
      medical professionals were scanned using resting state functional magnetic
      resonance imaging. Nine additional asymptomatic yet not medically cleared
      athletes were recruited to investigate the effect of a single episode of mTBI
      versus multiple mTBIs on the resting state DMN. In concussed individuals the
      resting state DMN showed a reduced number of connections and strength of
      connections in the posterior cingulate and lateral parietal cortices. An
      increased number of connections and strength of connections was seen in the
      medial prefrontal cortex. Connections between the left dorso-lateral prefrontal
      cortex and left lateral parietal cortex showed a significant reduction in
      magnitude as the number of concussions increased. Regression analysis also
      indicated an overall loss of connectivity as the number of mTBI episodes
      increased. Our findings indicate that alterations in the brain resting state
      default mode network in the subacute phase of injury may be of use clinically in
      assessing the severity of mTBI and offering some insight into the pathophysiology
      of the disorder.

PMID- 21846506
TI  - The inhibitory activity of Lactobacillus spp. isolated from breast milk on
      gastrointestinal pathogenic bacteria of nosocomial origin.
AB  - Milk acts as a mean for transporting many essential substances from the mother to
      the child. In human beings, milk includes several predominant bacteria, such as
      staphylococci, streptococci, micrococci, lactobacilli, enterococci, lactococci
      and bifidobacteria. Besides, its intake favors the predominance of bifidobacteria
      and lactobacilli in the child's intestinal microbiota. The present work explores
      the isolation and selection of lactobacilli strains with probiotic potential,
      focusing in their degree of hydrophobicity and antagonism against important
      gastrointestinal nosocomial pathogens. 98 lactobacilli were isolated from 48
      breast milk samples, with most strains belonging to the obligately
      homofermentative group (36.7%). 63% of the isolated strains showed a high degree
      of hydrophobicity when tested on three solvents and were selected for detecting
      antimicrobial activity against gastrointestinal pathogens, including Escherichia
      coli, Shigella spp, Pseudomonas spp and Salmonella spp strains. When applying the
      agar diffusion test, many isolated strains presented inhibitory activity against
      pathogenic strains. We observed that: Salmonella enteriditis was the most
      inhibited pathogen, and the strains with the most inhibitory power were AR2 and
      O1 (both highly hydrophobic lactic acid bacteria), which showed an opposing
      effect against all nosocomial pathogens tested. Although more in vitro, in vivo
      or clinical data would be needed before any conclusion on the probiotic
      properties of the strains can be drawn, our results demonstrate that some of the
      tested strains may have good probiotic potential for their inclusion in products
      targeting infants.

PMID- 21846507
TI  - Heart rate and hemocyte number as stress indicators in disturbed hibernating
      vineyard snails, Helix pomatia.
AB  - In humans and other vertebrates, mental or physical stressors may trigger a
      variety of symptoms generally referred to as the fight/flight response (Cannon
      1929). The processes also include variability of the heart frequency as well as
      leukocytosis. We monitored both body responses in disturbed hibernating vineyard
      snails, H. pomatia, to obtain information on the stress sensitivity of these
      "sleeping" invertebrates. The first mild stressor, a 100 meter transport of
      hibernating snails from the cold room to the laboratory, caused cardiac
      arrhythmia in the animals. This reaction could have been provoked by mechanical
      disturbances and/or by raising the body temperature to room temperature. But a
      change in the ambient temperature did not trigger an abnormal heart rhythm.
      Different from this observation, we recorded instant heart rate changes in
      response to knocking on the shell and a very irregular heartbeat occurred when a
      hole was punched in the shell. With a short time delay upon damaging the shell, a
      large increase in the number of circulating cells also occurred. This was not
      observed after knocking on the shell or when snails were adapted to different
      temperatures for each 48 h. Thus, hibernating snails sense environmental
      variations which cause an immediate change of the heart frequency and an elevated
      stimulus level initiates in addition leukocytosis which occurs at a post-stimulus
      latency. This disparity could indicate the activity of two different stress
      regulation pathways. Furthermore, the assays demonstrate an increasing linear
      relation between rising temperature and frequency of heart pulsations (y=1.01x
      2.1); but the results do not indicate a correlation between heartbeat frequency
      and the number of cells in circulation. Consequently, neither temperature nor
      heart frequency seems to influence the number of circulating cells in hibernating
      H. pomatia.

PMID- 21846505
TI  - Phenylephrine-modulated cardiopulmonary blood flow measured with use of X-ray
      digital subtraction angiography.
AB  - INTRODUCTION: Cardiopulmonary blood flow is an important indicator of organ
      function. Limitations in measuring blood flow in live rodents suggest that rapid
      physiological changes may be overlooked. For instance, relative measurements
      limit imaging to whole organs or large sections without adequately visualizing
      vasculature. Additionally, current methods use small samples and invasive
      techniques that often require killing animals, limiting sampling speed, or both.
      A recently developed high spatial- and temporal-resolution X-ray digital
      subtraction angiography (DSA) system visualizes vasculature and measures blood
      flow in rodents. This study was the first to use this system to measure changes
      in cardiopulmonary blood flow in rats after administering the vasoconstrictor
      phenylephrine. METHODS: Cardiopulmonary blood flow and vascular anatomy were
      assessed in 11 rats before, during, and after recovery from phenylephrine. After
      acquiring DSA images at 12 time points, a calibrated non-parametric deconvolution
      technique using singular value decomposition (SVD) was applied to calculate
      quantitative aortic blood flow in absolute metrics (mL/min). Trans-pulmonary
      transit time was calculated as the time interval between maximum signal
      enhancement in the pulmonary trunk and aorta. Pulmonary blood volume was
      calculated based on the central volume principle. Statistical analysis compared
      differences in trans-pulmonary blood volume and pressure, and aortic diameter
      using paired t-tests on baseline, peak, and late-recovery time points. RESULTS:
      Phenylephrine had dramatic qualitative and quantitative effects on vascular
      anatomy and blood flow. Major vessels distended significantly (aorta, ~1.2-times
      baseline) and mean arterial blood pressure increased ~2 times. Pulmonary blood
      volume, flow, pressure, and aortic diameter were not significantly different
      between baseline and late recovery, but differences were significant between
      baseline and peak, as well as peak and recovery time points. DISCUSSION: The DSA
      system with calibrated SVD technique acquired blood flow measurements every 30s
      with a high level of regional specificity, thus providing a new option for in
      vivo functional assessment in small animals.

PMID- 21846508
TI  - A case study of an EMR system at a large hospital in India: challenges and
      strategies for successful adoption.
AB  - This paper presents an ethnographically inspired interpretive case study of the
      Electronic Medical Record (EMR) system at Sankara Nethralaya hospital in India.
      It presents challenges related to the adoption of the system and methods and
      strategies that were utilized in order to overcome these challenges and help the
      system be adopted successfully. One of the more notable challenges at the
      hospital was a user base that included skeptical users, those lacking computing
      skills, and that had a history of rejecting designs. Despite these barriers the
      hospital was able to adopt the EMR system successfully. Notable issues related to
      the success of the system include the design strategy that was eventually used,
      and critical technical and social features of the system intended to support
      skeptical users and those lacking IT skills. The study contributes to overall
      understanding of the environment at large hospitals in developing countries as it
      relates to the adoption of EMR systems, and helps inform on methods that can be
      used to improve the adoption of EMR systems in similar contexts in both developed
      and developing countries.

PMID- 21846509
TI  - microRNAs as peripheral blood biomarkers of cardiovascular disease.
AB  - A host of studies have established essential roles for microRNAs in
      cardiovascular development and disease. Moreover, the discovery of stable
      microRNAs in bodily fluids indicated their potential as non-invasive biomarkers.
      In this review, we summarize the current studies describing microRNAs in blood
      cells or serum/plasma, as potential biomarkers of cardiovascular disease.

PMID- 21846511
TI  - Towards evidence-based medicine in surgical practice: best BETs.
AB  - Surgeons are faced with the dilemma that many clinical questions in their daily
      practice to do not have universally agreed answers, but patients increasingly
      demand the 'best practice' from their doctors. In addition time pressures mean
      that clinicians are unable to keep up with the full spectrum of published
      research. We have adopted an approach first pioneered in emergency medicine,
      namely the Best Evidence Topic or Best BET. Clinicians select a clinical scenario
      from their daily practice that highlights an area of controversy. From this, a
      three-part question is generated and this is used to search Medline and other
      appropriate databases for relevant papers. Once the relevant papers are found,
      these papers are critically appraised, the relevant data to answer the question
      is extracted, tabulated and summarised. A clinical bottom line is reached after
      this process. The resulting BETs, written by practising surgeons can then provide
      robust evidence-based answers to important clinical questions asked during our
      daily practice.

PMID- 21846510
TI  - Mechanical property characterization of electrospun recombinant human
      tropoelastin for vascular graft biomaterials.
AB  - The development of vascular grafts has focused on finding a biomaterial that is
      non-thrombogenic, minimizes intimal hyperplasia, matches the mechanical
      properties of native vessels and allows for regeneration of arterial tissue. In
      this study, the structural and mechanical properties and the vascular cell
      compatibility of electrospun recombinant human tropoelastin (rTE) were evaluated
      as a potential vascular graft support matrix. Disuccinimidyl suberate (DSS) was
      used to cross-link electrospun rTE fibers to produce a polymeric recombinant
      tropoelastin (prTE) matrix that is stable in aqueous environments. Tubular 1cm
      diameter prTE samples were constructed for uniaxial tensile testing and 4mm small
      diameter prTE tubular scaffolds were produced for burst pressure and cell
      compatibility evaluations from 15 wt.% rTE solutions. Uniaxial tensile tests
      demonstrated an average ultimate tensile strength (UTS) of 0.36+/-0.05 MPa and
      elastic moduli of 0.15+/-0.04 and 0.91+/-0.16 MPa, which were comparable to
      extracted native elastin. Burst pressures of 485+/-25 mm Hg were obtained from
      4mm internal diameter scaffolds with 453+/-74 MUm average wall thickness. prTE
      supported endothelial cell growth with typical endothelial cell cobblestone
      morphology after 48 h in culture. Cross-linked electrospun rTE has promising
      properties for utilization as a vascular graft biomaterial with customizable
      dimensions, a compliant matrix and vascular cell compatibility.

PMID- 21846512
TI  - Clinical and mutational spectrum in a cohort of 105 unrelated patients with
      dilated cardiomyopathy.
AB  - Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure with
      high morbidity and mortality. More than 30 genes have been reported to cause DCM.
      To provide new insights into the pathophysiology of dilated cardiomyopathy, a
      mutational screening on 4 DCM-causing genes (MYH7, TNNT2, TNNI3 and LMNA) was
      performed in a cohort of 105 unrelated DCM (64 familial cases and 41 sporadic
      cases) using a High Resolution Melting (HRM)/sequencing strategy. Screening of a
      highly conserved arginine/serine (RS)-rich region in exon 9 of RBM20 was also
      performed. Nineteen different mutations were identified in 20 index patients
      (19%), including 10 novels. These included 8 LMNA variants in 9 (8.6%) probands,
      5 TNNT2 variants in 5 probands (4.8%), 4 MYH7 variants in 3 probands (3.8%), 1
      TNNI3 variant in 1 proband (0.9%), and 1 RBM20 variant in 1 proband (0.9%). One
      proband was double-heterozygous. LMNA mutations represent the most prevalent
      genetic DCM cause. Most patients carrying LMNA mutations exhibit conduction
      system defects and/or cardiac arrhythmias. Our study also showed than prevalence
      of mutations affecting TNNI3 or the (RS)-rich region of RBM20 is lower than 1%.
      The discovery of novel DCM mutations is crucial for clinical management of
      patients and their families because pre-symptomatic diagnosis is possible and
      precocious intervention could prevent or ameliorate the prognosis.

PMID- 21846521
TI  - The Neonatal Resuscitation Program comes of age.

PMID- 21846524
TI  - Installation of home safety devices reduces incidence of preventable injury in
      young children.

PMID- 21846525
TI  - Omalizumab reduces frequency of asthma exacerbations in children.

PMID- 21846526
TI  - Inhaled corticosteroids are beneficial in treating asthma exacerbations in
      children with mild persistent asthma.

PMID- 21846527
TI  - Children under 2 years of age with acute otitis media benefit from antibiotic
      treatment.

PMID- 21846528
TI  - Evidence-based measures of normal heart and respiratory rates in children differ
      significantly with existing published data.

PMID- 21846529
TI  - Rapid antigen testing for respiratory virus syncytial can be used in neonates
      with provisos.

PMID- 21846530
TI  - Growth hormone therapy needs to be tailored based on individual responsiveness in
      children with idiopathic short stature.

PMID- 21846531
TI  - Top-cited articles in endodontic journals.
AB  - INTRODUCTION: The purpose of this study was to identify the 100 top-cited
      articles published in journals dedicated to endodontology and analyze their
      characteristics to describe the quality and evolution of research in the field of
      endodontology. METHODS: The Institute for Scientific Information Web of Knowledge
      Database and the Journal Citation Report Science Editions were used to retrieve
      the 100 most cited articles published in journals dedicated to endodontics. The
      top-cited articles were selected and analyzed with regard to journals, authors,
      institution, country of origin, publication title and year, number of citations,
      article type, study design, level of evidence, and field of study. RESULTS: The
      top 100 articles were cited between 87 and 554 times. These articles appeared in
      4 different journals, with more than half in the Journal of Endodontics, followed
      by the journals Oral Surgery Oral Medicine Oral Pathology Oral Radiology and
      Endodontology, the International Endodontic Journal, and Endodontics & Dental
      Traumatology. Forty-eight articles were published between 1990 and 1999. All
      articles were published in English and primarily originated from the United
      States (n = 52). The majority of articles were basic science articles (n = 55),
      followed by clinical research studies (n = 28) and nonsystematic reviews (n =
      17). Uncontrolled case series with level IV of evidence and narrative reviews
      with level V of evidence were the most frequent types of study design. The main
      topics covered by the top-cited articles were microleakage and endodontic
      microbiology. CONCLUSIONS: This analysis of citation rates reveals useful and
      interesting information about scientific progress in the field of endodontics.
      Basic research and observational studies published in high-impact endodontic
      journals had the highest citation rates.

PMID- 21846532
TI  - Survey of general dentists to identify characteristics associated with increased
      referrals to endodontists.
AB  - INTRODUCTION: Few studies have surveyed dentists in general practice (GPs) to
      assess their perceptions and understand the factors associated with referrals to
      endodontists. The purpose of the study was to understand the referral behavior of
      GPs by examining the effects of endodontist characteristics and professional
      behavior and the role of GP demographics and perceptions in determining referrals
      to endodontists. METHODS: Researchers conducted a cross-sectional study that
      included a quantitative online survey of 983 GPs in the United States from
      November 4-18, 2009. RESULTS: Ninety-four percent of the GPs had positive
      perceptions of endodontists, but they only referred 46% of patients who required
      root canal treatment to endodontists. The perception that endodontists are
      partners in patient care and endodontic services are worth the cost was strongly
      related to the likelihood of referring (P < .05). GPs rated timely follow-up of
      reports and images (96%; n = 935), referring patients back for restorative
      treatment (94%; n = 916), and patient scheduling accommodation (92%; n = 900) as
      effective ways to build partnerships. Gender and years in practice moderated the
      relationships between several predictors (eg, communication, patient care, value
      of treatment, and expertise) and the likelihood of referring. CONCLUSIONS: There
      are concrete actions endodontists can take and segments of the GP population that
      can be targeted to successfully address the issue of increasing referrals, but
      this is only the first step in addressing the complex relationships involved in
      referral behavior.

PMID- 21846533
TI  - Pulp vitality in patients with intraoral and oropharyngeal malignant tumors
      undergoing radiation therapy assessed by pulse oximetry.
AB  - INTRODUCTION: The aim of this study was to evaluate pulp oxygenation levels
      (%SpO(2)) in patients with malignant intraoral and oropharyngeal tumors treated
      by radiotherapy (RT). METHODS: Pulp oxygenation levels were measured by pulse
      oximetry. Twenty patients were selected, and two teeth of each participant (n =
      40) were analyzed, regardless of the quadrant and the area irradiated, at four
      different time points: TP1, before RT; TP2, at the beginning of RT with radiation
      doses between 30 and 35 Gy; TP3, at the end of RT with radiation doses between 60
      and 70 Gy; and TP4, 4 to 5 months after the beginning of cancer treatment.
      RESULTS: Mean %SpO(2) at the different time points were 93% (TP1), 83% (TP2), 77%
      (TP3), and 85% (TP4). The Student's t test showed statistically significant
      differences between TP1 and TP2 (P < .01), TP3 (P < .01), and TP4 (P < .01). TP3
      was also statistically significantly different when compared with TP2 (P < .01)
      and TP4 (P < .01). No statistically significant difference could be observed
      between TP2 and TP4. CONCLUSIONS: Because the mean %SpO(2) before RT was greater
      than during and after therapy and values obtained 4 to 5 months after the
      beginning of RT were close to the initiation of RT, pulp tissue may be able to
      regain normal blood flow after RT. If the changes in the microcirculation of the
      dental pulp were indeed transitory, preventive endodontic treatment or extraction
      in patients who are currently undergoing or recently received RT and who show
      negative signs of pulp sensitivity may not be necessary for pulpal reasons.

PMID- 21846534
TI  - Endodontic pathogens causing deep neck space infections: clinical impact of
      different sampling techniques and antibiotic susceptibility.
AB  - INTRODUCTION: The aims of the present study were to compare microbial populations
      in patients suffering from deep neck space abscesses caused by primary endodontic
      infections by sampling the infections with aspiration or swabbing techniques and
      to determine the susceptibility rates of the isolated bacteria to commonly used
      antibiotics. METHODS: A total of 89 patients with deep neck space abscesses
      caused by primary endodontic infections requiring extraoral incision and drainage
      under general anesthesia were included. Either aspiration or swabbing was used to
      sample microbial pus specimens. The culture of the microbial specimens and
      susceptibility testing were performed following standard procedures. RESULTS: A
      total of 142 strains were recovered from 76 patients. In 13 patients, no bacteria
      were found. The predominant bacteria observed were streptococci (36%),
      staphylococci (13%), Prevotella (8%), and Peptostreptococcus (6%). A
      statistically significant greater number of obligate anaerobes were found in the
      aspiration group. The majority of patients presented a mixed aerobic-anaerobic
      population of bacterial flora (62%). The antibiotic resistance rates for the
      predominant bacteria were 10% for penicillin G, 9% for amoxicillin, 0% for
      amoxicillin clavulanate, 24% for clindamycin, and 24% for erythromycin.
      CONCLUSIONS: The results of our study indicated that a greater number of
      anaerobes were found when sampling using the aspiration technique. Penicillin G
      and aminopenicillins alone are not always sufficient for the treatment of severe
      deep neck space abscesses; beta-lactamase inhibitor combinations are more
      effective. Bacteria showed significant resistant rates to clindamycin. Thus, its
      single use in penicillin-allergic patients has to be carefully considered.

PMID- 21846535
TI  - Analysis of symptomatic and asymptomatic primary root canal infections in adult
      Norwegian patients.
AB  - INTRODUCTION: This molecular study analyzed the microbiota of primary root canal
      infections from adult Norwegian patients. METHODS: Samples were taken from the
      necrotic root canals of teeth with symptomatic (n = 13) or asymptomatic (n = 21)
      apical periodontitis and chronic apical abscesses (n = 9). DNA was extracted from
      samples, and bacterial identifications were performed by a closed-ended reverse
      capture checkerboard approach targeting 50 candidate endodontic pathogens.
      RESULTS: Bacterial DNA was detected in all cases. In teeth with asymptomatic
      apical periodontitis, the most frequent taxa were Dialister invisus (71%),
      Fusobacterium nucleatum (62%), and Porphyromonas endodontalis (62%). In chronic
      apical abscesses, the most prevalent taxa were P. endodontalis (100%), D. invisus
      (89%), Parvimonas micra (78%), and Solobacterium moorei (78%). In teeth with
      symptomatic apical periodontitis, the most prevalent taxa were D. invisus, P.
      endodontalis, S. moorei, Propionibacterium acnes, and Streptococcus species (all
      in 69%). None of the targeted taxa were significantly associated with either
      sinus tract or pain (P > .05), except for Selenomonas sputigena, which was more
      frequently found in painful cases (P = .04). No taxa were found in significantly
      higher levels in any conditions (P > .05). Cluster analyses revealed bacterial
      groupings that differed between cases with and without pain. CONCLUSIONS:
      Although basically the same species were highly prevalent in the different
      conditions examined and none of the most prevalent taxa were positively
      associated with symptoms, results revealed that species formed different
      partnerships and associations in samples from teeth with or without pain.
      Therefore, it is possible that more virulent multispecies communities can form as
      a result of overall bacterial combinations and give rise to acute inflammation.

PMID- 21846536
TI  - Accuracy of Root ZX II in locating foramen in teeth with apical periodontitis: an
      in vivo study.
AB  - INTRODUCTION: This study was conducted in vivo to investigate the accuracy of
      Root ZX II in locating the apical foramen in teeth with apical periodontitis
      (AP). METHODS: Twenty-seven single-root teeth scheduled for extractions were
      selected; in AP group, there were 12 teeth with pulp necrosis and radiographic
      evidence of apical lesions, and VT group consisted of 15 vital teeth. After
      endodontic access, the coronal portion of the canal was flared, and electronic
      measurement was performed by using a 15 K-file until the device level reading
      "APEX" was reached. The file was fixed in place, and the tooth was extracted. The
      apical third of the root was shaved until exposure of the file. The distance from
      the file tip to the most coronal border of the apical foramen was obtained.
      RESULTS: The mean distance in AP group was +0.117 (standard deviation, 0.373) and
      in VT group was -0.105 (standard deviation, 0.218). The unpaired t test showed no
      difference between the groups when comparing the mean distances (P > .05). The
      apical foramen was accurately located within +/-0.5 mm in 83% of the teeth in AP
      group and in 100% of VT group. Statistical analysis showed no difference between
      the groups (P = .1092). CONCLUSIONS: The Root ZX II device was accurate in
      locating the apical foramen regardless of the presence of AP.

PMID- 21846537
TI  - Cells isolated from inflamed periapical tissue express mesenchymal stem cell
      markers and are highly osteogenic.
AB  - INTRODUCTION: We previously reported the presence of mesenchymal stem/progenitor
      cells (MSCs) in inflamed pulp tissue. Here we asked whether MSCs also exist in
      inflamed periapical tissues resulting from endodontic infection. The objectives
      of this study were to detect the expression of MSC markers in periapical
      inflammatory tissues and to characterize isolated cells from these tissues.
      METHODS: Human periapical inflammatory tissues were collected and processed to
      detect MSC marker expression by immunohistochemistry. Cells were isolated and
      tested for cell surface marker expression by using flow cytometry and examined
      for multiple differentiation potential into osteogenic and adipogenic pathways.
      In vivo formation of mineralized tissues was assessed in a mouse model. RESULTS:
      Immunohistochemistry showed positive staining for MSC markers STRO-1, CD90, and
      CD146. Isolated cells at passage 0 appeared as typical fibroblastic cells, and a
      few cells formed colony-forming unit-fibroblasts (CFU-Fs). After passaging, the
      CFU-F forming ability diminished dramatically, and the population doubling was up
      to 26. Flow cytometry data showed that these cells at passage 2 expressed low
      levels of STRO-1 and CD146 and moderate to high levels of CD90, CD73, and CD105.
      At passage 6, the levels of these markers decreased. When incubated in specific
      differentiation medium, cells demonstrated a strong osteogenic but weak
      adipogenic capacity. After in vivo cell transplantation, mineralized tissues
      formed in immunocompromised mice. CONCLUSIONS: Human periapical inflammatory
      tissues expressed MSC markers, suggesting the presence of MSCs. Isolated cells
      exhibited typical mesenchymal cell immunophenotype with a capacity to form
      mineralized matrix in vitro and in vivo.

PMID- 21846538
TI  - In vivo host interactions with mineral trioxide aggregate and calcium hydroxide:
      inflammatory molecular signaling assessment.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) and calcium hydroxide [Ca(OH)(2)]
      are promising biomaterials for stimulating dentinogenesis and cementogenesis.
      This research was undertaken to understand how MTA and CA(OH)(2) participate in
      the inflammatory, healing, and biomineralization processes. In this part of the
      study, we evaluated inflammatory signaling molecules promoted by in vivo host
      interaction with MTA and Ca(OH)(2). METHODS: Human dentin tubes were filled with
      ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), Ca(OH)(2), or kept empty. After
      12 hours and 1, 3, 7, 15, 30, and 60 days of implantation in subcutaneous tissues
      in the backs of mice, the tubes and surrounding tissues were retrieved for
      cytokine level quantification and histological and immunohistochemical analysis.
      RESULTS: MTA and Ca(OH)(2) induced proinflammatory cytokine up-regulation for up
      to 3 days. Moreover, interleukin-10 overexpression was noted on the tissue in
      contact with the biomaterials during the acute phase of the inflammatory
      reaction. Immunohistochemical analyses showed an increased expression of
      myeloperoxidase, nuclear factor kappa B (NF-kappaB), cyclooxygenase-2, inducible
      nitric oxide synthase enzymes, and vascular endothelial growth factor on day 1
      for all groups. CONCLUSIONS: MTA and Ca(OH)(2) increased the activation of the NF
      kappaB signaling system on day 1 for all groups. This finding can be associated
      with a proinflammatory and pro-wound healing environment, which was promoted
      earlier by MTA.

PMID- 21846539
TI  - Proliferation of mature ex vivo human dental pulp using tissue engineering
      scaffolds.
AB  - INTRODUCTION: The purpose of this study was to measure and compare the
      proliferation of mature human dental pulp tissue using three types of tissue
      engineering scaffolds. METHODS: Mature human teeth were collected immediately
      after extraction for routine dental treatment reasons. Three types of tissue
      engineering scaffolds were investigated (1) open-polylactic acid (polymer)
      scaffolds, (2) bovine collagen (collagen) scaffolds, and (3) calcium phosphate
      bioceramic (calcium phosphate) scaffolds. The scaffolds were placed in direct
      contact with the dental pulp of the tooth slices from 7 to 30 days. Neutral-red
      dye was added to the culture media to stain metabolically active cells. The
      specimens were processed for histology. The numbers of proliferating cells were
      counted per unit area of scaffold according to ISO criteria. RESULTS: The
      proliferating dental pulp cells had a fibroblast phenotype, no cells of other
      phenotypes were observed, and none of the cells appeared to be mineralizing. The
      average rate of mature vital dental cell proliferation was 1.305 cells per day in
      the calcium phosphate scaffolds compared with 7.195 (a rate increase of 551%) in
      the collagen scaffolds and 13.885 (a rate increase of 1,064%) in the polymer
      scaffolds. CONCLUSIONS: Tissue engineering scaffolds can enhance the
      proliferation of mature dental pulp tissue. The rate of dental pulp proliferation
      is dependent on the chemical composition of the scaffold. Within the limitations
      of this study, the polymer scaffolds were more optimal than collagen or calcium
      phosphate scaffolds for mature dental pulp proliferation.

PMID- 21846540
TI  - Effect of tricalcium silicate on the proliferation and odontogenic
      differentiation of human dental pulp cells.
AB  - INTRODUCTION: This study was to investigate the effects of tricalcium silicate
      (Ca(3)SiO(5)) on proliferation and odontogenic differentiation of human dental
      pulp cells (hDPCs) in vitro. METHODS: The hDPCs were seeded in culture medium
      with or without Ca(3)SiO(5) extract and calcium hydroxide (Ca(OH)(2)) extract.
      Proliferation of the hDPCs was measured by methyl-thiazol-tetrazolium (MTT)
      assay. Odontogenic differentiation of hDPCs was evaluated by real-time polymerase
      chain reaction by using odontogenic marker genes such as dentin
      sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP 1), osteocalcin (OC),
      alkaline phosphatase (ALP), and collagen type I (Col I), which were verified by
      ALP activity assessment, mineralization assay, and immunocytochemistry staining
      for dentin sialoprotein (DSP). RESULTS: The MTT assay showed that hDPCs cultured
      with Ca(3)SiO(5) extract proliferated more significantly as compared with
      Ca(OH)(2) extract. Analysis of odontogenic marker genes indicated that
      Ca(3)SiO(5) enhanced the expression of those genes. Moreover, the extract of
      Ca(3)SiO(5) stimulated mineralization and increased ALP and DSP production
      conspicuously. CONCLUSIONS: These results reveal that Ca(3)SiO(5) can induce the
      proliferation and odontogenic differentiation of hDPCs in vitro and might be a
      potential candidate for preparation of a new type of Ca(3)SiO(5-)based cement as
      a pulp-capping agent.

PMID- 21846541
TI  - Bacterial and Candida albicans adhesion on different root canal filling materials
      and sealers.
AB  - INTRODUCTION: Microbial adhesion and subsequent biofilm formation on endodontic
      root canal filling materials and sealers lead to survival of microorganisms in
      treated root canals and subsequently to endodontic treatment failures. The
      present study focused on initial microbial adhesion to different endodontic
      filling materials. METHODS: The following endodontic biomaterials were tested: AH
      Plus, Tubli Seal, gutta-percha, Real Seal SE, EndoREZ, Apexit Plus, GuttaFlow,
      and dentin. Samples of each material were prepared. Bovine dentin samples were
      used as a control. The initial adhesions of salivary bacteria as well as the
      subsequent single species were quantified by determination of colony-forming
      units (CFUs) and visualized by scanning electron microscopy and confocal
      microscopy (CLSM): Enterococcus faecalis, Streptococcus mutans, Streptococcus
      sanguis, Candida albicans, and Prevotella nigrescens. RESULTS: Initially adherent
      microorganisms could be detected and microscopically visualized on each of the
      materials tested. Considering the values of the CFUs and the covering grade as
      detected by CLSM, there were significant differences among the materials. Fewer
      bacteria tended to adhere to Apexit Plus, whereas Real Seal SE and the widely
      used gutta-percha showed the highest number of adherent bacteria. This tendency
      was not detected for C. albicans. CONCLUSIONS: Endodontic microorganisms have a
      high affinity to root canal filling materials and sealers, especially to gutta
      percha. Because of this high level of bacterial adhesion, subsequent biofilm
      formation on these materials could be suggested as leading to the persistence of
      microorganisms in root canals.

PMID- 21846542
TI  - Effectiveness of the proton pump inhibitor omeprazole associated with calcium
      hydroxide as intracanal medication: an in vivo study.
AB  - INTRODUCTION: The objective of this study was to evaluate the efficacy of the
      association of a proton pump inhibitor (omeprazole) with Ca(OH)(2) as intracanal
      medication in a rat model of periapical lesions. METHODS: Periapical lesions were
      induced on the first right mandibular molar tooth of 36 male Wistar rats (6 per
      group). After 28 days, the distal canal of each tooth was prepared, filled with
      the respective dressing (negative control group, PEG 400; positive control group,
      Ca(OH)(2) + PEG400; test group, Ca(OH)(2) + omeprazole + PEG 400), and sealed
      with amalgam for 15 or 28 days. Microbiological samples were taken in 3 periods:
      S1, after 28 days of lesion induction; S2, after the biomechanical preparation;
      and S3, after the medication (15 and 28 days). RESULTS: The radiographic and
      histologic analysis revealed that either Ca(OH)(2) or Ca(OH)(2) plus omeprazole
      dressings produced a reduction of periapical lesions at 28 days, when compared
      with the negative control group. The reduction of periapical lesions and
      inflammatory cell infiltration was visibly improved by associating omeprazole
      with Ca(OH)(2), with an increase of reparative bone areas. The microbiological
      assessment showed a significant decrease of colony-forming units count from S1 to
      S2 or S3 collecting times, but no differences were observed between the S2 and
      the S3 time-periods or among the experimental groups within the S3 period.
      Further bacterial characterization showed a possible selective activity of the
      medications. CONCLUSIONS: Our data showed that association of omeprazole with
      Ca(OH)(2) favored a superior repair of rat periapical lesions and seemed to
      display different selective activity over endodontic microbiota, in comparison
      with the conventional Ca(OH)(2) dressing.

PMID- 21846543
TI  - Gene expression analysis of resident macrophages in lipopolysaccharide-stimulated
      rat molar pulps.
AB  - INTRODUCTION: In normal dental pulp, a considerable number of resident
      macrophages are distributed. This study was designed to analyze the expression
      levels of genes associated with differentiation and function of resident
      macrophages in rat molar pulps stimulated with lipopolysaccharide (LPS). METHODS:
      Mandibular first molars of 7-week-old male Wistar rats were used. After
      transcardiac perfusion with a culture medium to preserve tissue integrity,
      pulpotomy and LPS application were carried out on the experimental teeth, and
      then dissected mandibles were subjected to whole-tooth culture for 3 days. Normal
      teeth and pulpotomized teeth without LPS served as controls. The specimens were
      then immunostained for ED1 (CD68, a general macrophage marker) and ED2 (CD163, a
      resident macrophage marker). Real-time polymerase chain reaction for Toll-like
      receptor 4 (TLR4), CD14, chemokine receptors (CCR2 and CX3CR1), and colony
      stimulating factor-1 (CSF1) mRNAs was carried out after laser capture
      microdissection of ED1+ and ED2+ cells. RESULTS: LPS-treated pulps showed
      significant increases in (1) density of ED1+ and ED2+ cells beneath the
      amputation site and (2) expression levels of TLR4, CD14, CSF1, and CX3CR1 mRNAs,
      as compared with non-LPS-treated groups. CCR2 mRNA showed no significant
      difference between each group. CONCLUSIONS: LPS treatment of cultured rat molars
      caused the accumulation of resident macrophages and enhanced the expression of
      TLR4, CD14, CSF1, and CX3CR1 mRNAs in these cells. Up-regulation of these
      molecules might be involved in the differentiation and subsequent migration of
      resident macrophages of the pulp.

PMID- 21846544
TI  - A novel methodology to evaluate the use of an ultrasonic tip.
AB  - INTRODUCTION: The purpose of this in vitro investigation was to use a novel
      methodology to evaluate the use of an endodontic ultrasonic (US) tip. METHODS:
      BUC 1 US tips (n = 10) were mounted to a testing apparatus that applied a linear
      movement of the US tip to dentin specimens with an axial force of 15 g.
      Instrumentation was activated for 20-second cycles up to a 2-minute baseline and
      continued for 10-minute intervals up to a defined inefficient/dropout point.
      Dentin cutting efficiency was measured by the change in weight of dentin
      specimens to the nearest 0.01 mg. A quantitative analysis was conducted on length
      and diameter of the US tips by using images taken at 15.625 magnification and
      1000 pixels/cm (1 pixel = 0.01 mm) resolution. Weight of dentin specimens and
      images were captured at 2, 50, 100, 150, and 190 minutes of instrumentation.
      RESULTS: There was no statistically significant difference in dentin removal
      between measurement times for any US tip specimen. There was a statistically
      significant difference in tip length over time (P = .002). Tukey post hoc
      analysis revealed that tip length decreased significantly at 2 minutes of
      instrumentation. CONCLUSIONS: Within the limits of this investigation, the BUC 1
      US tip did not significantly decrease in efficiency between 2 and 190 minutes of
      use. The decrease in tip length was found to be significant at 2 minutes of
      instrumentation. Adding a linear movement, in addition to an axial force, for
      testing US tips will make future investigations more clinically relevant.

PMID- 21846545
TI  - Qualitative analysis of the removal of the smear layer in the apical third of
      curved roots: conventional irrigation versus activation systems.
AB  - INTRODUCTION: The aim of this study was to evaluate the effectiveness of
      different irrigant agitation techniques on smear layer removal in curved root
      canals. METHODS: Mesiobuccal canals of 62 extracted lower molars with a curvature
      of 33 degrees were used and instrumented up to ProTaper F2. The samples were
      divided into 3 experimental groups according to the final irrigation:
      conventional irrigation, ultrasonic irrigation, and sonic irrigation by using the
      EndoActivator system. The control group was composed of 2 specimens without any
      final irrigation. In all of the experimental groups, 5 mL of 17%
      ethylenediaminetetraacetic acid was used for 1 minute, and 5 mL of 2.5% NaOCl was
      used for 30 seconds. The analysis of the apical region was performed via scanning
      electron microscopy by 3 examiners. The data were submitted to the Kruskal-Wallis
      and Dunn tests (P < .05). RESULTS: The activation systems removed significantly
      more smear layer than did conventional irrigation. CONCLUSIONS: Sonic and
      ultrasonic irrigation resulted in better removal of the smear layer in the apical
      third of curved root canals than did conventional irrigation.

PMID- 21846546
TI  - Efficacy of different final irrigation activation techniques on smear layer
      removal.
AB  - INTRODUCTION: Different techniques and irrigant delivery devices have been
      proposed to increase the flow and distribution of irrigating solutions within the
      root canal system. The aim of this study was to compare smear layer removal after
      final irrigant activation with apical negative pressure (ANP), manual dynamic
      agitation (MDA), and passive ultrasonic irrigation (PUI). METHODS: Forty single
      rooted human mandibular premolars were decoronated to a standardized length of 16
      mm. They were cleaned and shaped by using ProTaper system to size F4 and NaOCl
      2.5%. The specimens were divided into 4 equal groups (n = 10) according to the
      final irrigation activation technique: group 1, passive irrigation (PI); group 2,
      apical negative pressure (ANP) (EndoVac); group 3, manual dynamic activation
      (MDA); and group 4, passive ultrasonic irrigation (PUI). Samples were split
      longitudinally and examined under scanning electron microscope for smear layer
      presence. RESULTS: PI and PUI had the highest smear scores, with no significant
      differences between them. This was followed by MDA and finally ANP, which showed
      the statistically significant lowest mean score at P <= .05. CONCLUSIONS: Final
      irrigant activation with ANP and MDA resulted in better removal of the smear
      layer than with PUI or PI.

PMID- 21846547
TI  - Effect of maintaining apical patency on irrigant penetration into the apical
      third of root canals when using passive ultrasonic irrigation: an in vivo study.
AB  - INTRODUCTION: The complex anatomy of the root canal system has been shown to
      limit the penetration of irrigating solutions into the apical third; hence, the
      aim of this study was to determine whether the use of a patency file is related
      to the presence of a radiopaque irrigating solution in the apical third of human
      root canals after using passive ultrasonic activation in vivo. METHODS: Forty
      human root canals were randomly divided into two groups. Apical patency was
      maintained in one group (n = 21) during shaping and cleaning procedures with a
      no. 10 K-file 1 mm beyond the working length (WL) but not in the other group (n =
      19). In both groups, the canals were shaped with the Pro Taper system (Dentsply
      Maillefer, Ballaigues, Switzerland). Irrigation was performed with 1 mL of a
      solution prepared with a radiopaque contrast medium and sodium hypochlorite
      5.25%, and then passive ultrasonic irrigation (PUI) was applied after the shaping
      procedure. Digital images were taken, and a calibrated reader determined the
      presence or absence of the irrigating solution in the apical third. RESULTS:
      There were significantly more canals with irrigant in the apical third after PUI
      when apical patency was maintained with a no. 10 file 1 mm beyond the WL than
      when apical patency was not maintained throughout the cleaning and shaping
      procedures (P = .02). CONCLUSIONS: Maintaining apical patency and then using PUI
      improves the delivery of irrigants into the apical third of human root canals.

PMID- 21846548
TI  - Cleaning efficacy using two engine-driven systems versus manual instrumentation
      in curved root canals: a scanning electron microscopic study.
AB  - INTRODUCTION: This ex vivo study evaluated the cleanliness of curved root canal
      walls after chemomechanical instrumentation using two automated systems versus
      manual instrumentation while using a standardized irrigation protocol. METHODS:
      Thirty mesial root canals of extracted human first and second mandibular molars
      were prepared with the TiLOS hybrid engine-driven instrumentation system
      (Ultradent Products Inc, South Jordan, UT) (n = 10), ProTaper engine-driven file
      series (n = 10), and manual instrumentation (n = 10). Irrigation was performed
      using alternately 5.25% sodium hypochlorite and 17% EDTA followed by rinsing with
      distilled water. After the roots were split longitudinally, the presence of
      debris and/or smear layer was visualized using serial scanning electron
      microscopic digital photomicrographs taken at 1, 5, and 10 mm from the working
      length. Mean scores for debris and the smear layer were calculated and
      statistically analyzed for significance (P < .05) between groups using the
      Kruskal-Wallis nonparametric analysis of variance and Dunn tests. The data
      obtained at each evaluation level for each group were analyzed using the Friedman
      and Tukey multiple comparison tests. RESULTS: No significant differences (P >
      .05) were found between TiLOS and ProTaper (Dentsply/Tulsa Dental, Tulsa, OK)
      groups, whereas both performed significantly better than the manual
      instrumentation group. CONCLUSIONS: Engine-driven TiLOS and ProTaper
      instrumentation systems combined with a standardized irrigation protocol produced
      cleaner root canal walls than the manual instrumentation technique although
      complete cleanliness was not achieved.

PMID- 21846549
TI  - Comparison of torsional stiffness of nickel-titanium rotary files with different
      geometric characteristics.
AB  - INTRODUCTION: The aim of this study was to evaluate the theoretical effect from
      pitch and cross-sectional geometry on torsional stiffness of nickel-titanium
      (NiTi) instruments. METHODS: Finite element models of NiTi rotary instruments
      with different cross-sectional geometries and different number of threads were
      made for comparison of torsional stiffness. Four cross-sectional shapes were
      tested: triangle, slender rectangle, rectangle, and square. Taper and external
      peripheral radius were the same for all models, whereas cross-sectional area
      and/or center core area were varied. Three pitch values (5, 10, and 15 threads)
      were tested for each type of cross-sectional geometry. The torsional stiffness of
      the 12 resulting finite element models was calculated by twisting the file shanks
      20 degrees while holding the file tip at apical 4 mm. RESULTS: The file models
      with larger pitch (fewer threads) had lower torsional stiffness. The models with
      the rectangular cross section had higher torsional stiffness than models with the
      triangular cross section, even when the cross-sectional areas were the same or
      the center core area was smaller. File models with larger cross-sectional area
      had higher torsional stiffness. CONCLUSIONS: Torsional deformation and/or
      fracture of NiTi rotary files might be reduced by reducing the pitch (increasing
      the number of threads) and increasing the cross-sectional areas rather than the
      center core area.

PMID- 21846550
TI  - Comparative evaluation of propolis and triantibiotic mixture as an intracanal
      medicament against Enterococcus faecalis.
AB  - INTRODUCTION: The aim of this study was to evaluate and compare the antimicrobial
      activity of calcium hydroxide, triantibiotic mixture (TAM), and an ethanol
      extract of propolis as intracanal medicaments on Enterococcus faecalis-infected
      root canals. METHODS: One hundred twenty extracted intact human permanent
      incisors were decoronated, and chemomechanical preparation of the root canal was
      performed. After sterilization of the samples, they were inoculated with pure
      culture of E. faecalis and incubated. After incubation, colony-forming units were
      recorded before medication. Then, samples were divided randomly into five groups
      (n = 24). Each group was then exposed to various intracanal medicaments, namely
      calcium hydroxide (group 1), TAM (group 2), propolis (group 3), ethanol (group
      4), and saline as the control group (group V). The antibacterial effectiveness of
      the different intracanal medicament was recorded by determining the percentage
      reduction in colony counts (%RCC) at the end of days 1, 2, and 7. The data were
      statistically analyzed using one-way analysis of variance and Tukey Honestly
      Significant Difference (HSD) post hoc test. RESULTS: The %RCC was highest for
      propolis showing 100% reduction on day 2 followed by TAM showing 82.5%, 92.2%,
      and 98.4% of reduction on days 1, 2, and 3, respectively. Calcium hydroxide
      showed a gradual increase in antibacterial activity with a maximum of 59.4% on
      day 7. CONCLUSIONS: Propolis was more effective than TAM against E. faecalis at a
      2-day time period, and both were equally effective at 7 days.

PMID- 21846551
TI  - Comparison of canal transportation and changes in canal curvature of two nickel
      titanium rotary instruments.
AB  - INTRODUCTION: The aim of this study was to compare the canal transportation and
      changes in canal curvature after canal preparation with 2 nickel-titanium (NiTi)
      rotary instruments, Twisted (TF) and K3 file systems. METHODS: Forty mandibular
      molar canals with angles of curvature between 25 and 35 degrees were randomly
      divided into 2 groups. Canals in K3 group were instrumented by using K3 rotary
      system. Canals in TF group were instrumented by using TF rotary system. All
      canals were instrumented with crown-down methodology to working length at a speed
      of 350 rpm and a torque-control level of 3 by using an 8:1 reduction handpiece.
      The final apical preparation was set to #30 in both groups. By using a
      radiographic platform, reproducible preinstrumentation and postinstrumentation
      radiographs were taken. The difference between the preinstrumentation and
      postinstrumentation angles was calculated and statistically analyzed by using
      unpaired t test. RESULTS: TF recorded statistically significant lower percentage
      of change in canal curvature (-2.99%) than K3 group (P < .05). CONCLUSIONS: TF
      system produced significantly less transportation and preserved the original
      canal to a greater degree than did the K3 system.

PMID- 21846552
TI  - Bending properties of a new nickel-titanium alloy with a lower percent by weight
      of nickel.
AB  - INTRODUCTION: The aim of the present study was to evaluate the bending properties
      of Hyflex instruments, which exhibit a lower percent in weight of nickel (52 Ni
      %wt) and compare them with other commercially available nickel-titanium (NiTi)
      rotary instruments. METHODS: Ten instruments with tip size 25, 0.06 taper of each
      of the following NiTi rotary instrumentation techniques were selected for the
      study: Hyflex, EndoSequence, ProFile, Hero, and Flexmasters. All instruments from
      each group were tested for stiffness by comparing their bending moment when they
      attained a 45-degree bend. Experimental procedures strictly followed testing
      methodology described in ISO 3630-1. All data were recorded and subjected to
      statistical evaluation by using analysis of variance test. Statistical
      significance was set at P < .05). RESULTS: Statistical analysis of the data
      revealed that Hyflex files were found to be the most flexible instruments, with a
      significant difference (P < .05) in comparison with the other instruments. Among
      the other files, a significant difference has been reported for EndoSequence
      instruments compared with ProFile, Hero, and FlexMaster (P < .05), whereas no
      significant differences have been reported among those 3 files (P > .05).
      CONCLUSIONS: Results of the present study have illustrated an increased
      flexibility of the new NiTi alloy over conventional NiTi alloy, and they
      highlight the potential of the new manufacturing process.

PMID- 21846553
TI  - Shaping ability of reciprocating motion in curved root canals: a comparative
      study with micro-computed tomography.
AB  - INTRODUCTION: Recently, root canal shaping with reciprocating motion has been
      postulated to reduce the possibility of unexpected file fractures. However, there
      has been little information on the shaping capability of this reciprocating
      motion preparation technique. Therefore, the purpose of this study was to
      evaluate the shaping ability of reciprocating motion when compared with
      continuous rotation motion in curved root canals. METHODS: The mesiobuccal and
      distobuccal canals of 20 extracted maxillary molars with curvatures of 20-45
      degrees were instrumented with a series of ProTaper rotary files. The canals in
      the continuous rotation motion (CM) group (n = 20) were prepared by using
      continuous rotation with pecking motion, whereas the canals in the reciprocating
      motion (RM) group (n = 20) were prepared with reciprocating motion (clockwise 140
      degrees and counterclockwise 45 degrees). Basic geometric parameters such as
      curvature, root canal volume, surface area, and structure model index (SMI)
      before and after canal shaping were evaluated by using micro-computed tomography.
      The degrees and directions of transportation were also measured, and statistical
      analysis was carried out with one-way analysis of variance and Tukey post hoc
      tests. RESULTS: There were no significant differences between the 2 groups in
      canal curvature, volume, surface area, and SMI categories measured before
      preparation (P > .05). Changes in curvature, root canal volume, surface area, and
      SMI were not affected by the instrumentation technique used (P > .05). There were
      no significant differences in the degrees and directions of transportation
      between CM and RM groups (P > .05). CONCLUSIONS: The application of reciprocating
      motion during instrumentation did not result in increased apical transportation
      when compared with continuous rotation motion, even in the apical part of curved
      canals. Reciprocating motion might be an attractive alternative method to prevent
      procedural errors during root canal shaping.

PMID- 21846554
TI  - Comparison of debris removal with three different irrigation techniques.
AB  - INTRODUCTION: The purpose of this study was to compare the effectiveness of
      debris removal between EndoVac, PiezoFlow, or needle irrigation (Max-i-Probe) in
      mandibular molars. METHODS: The mesial roots of 30 extracted mandibular molars
      were mounted in resin by using the K-Kube and then sectioned at 2 and 4 mm from
      the apex. The specimens were reassembled and instrumented to size 40/0.04. A
      standard irrigation protocol was used during instrumentation in the PiezoFlow and
      Max-i-Probe groups. During instrumentation of teeth in the EndoVac group, the
      manufacturer's recommendations for irrigation were followed. Images of the canals
      and isthmuses were taken before final irrigation. The percentage of cleanliness
      for each canal and isthmus was calculated by using interactive software. The
      specimens were reassembled for final irrigation with EndoVac, PiezoFlow, and Max
      i-Probe by using similar volumes of irrigants. Images were again used to
      calculate cleanliness. Comparisons of canal and isthmus cleanliness before and
      after final irrigation were made by using paired t tests, and the groups were
      compared with repeated-measures analysis of variance (P < .05). RESULTS: There
      were no statistically significant differences in canal and isthmus cleanliness
      among all 3 groups at 2 and 4 mm from working length before or after final
      irrigation. Canal and isthmus cleanliness significantly improved at all levels
      after the final irrigation regimen in each group. CONCLUSIONS: Final irrigation
      by using EndoVac, the PiezoFlow, or Max-i-Probe with similar volumes of irrigants
      significantly improved canal and isthmus cleanliness.

PMID- 21846555
TI  - Critical diameter of apical foramen and of file size using the Root ZX apex
      locator: an in vitro study.
AB  - INTRODUCTION: An evaluation was made of the accuracy of the Root ZX apex locator
      (J. Morita Corp, Tokyo, Japan) in widened foramina, considering the existing
      controversy over this issue in the literature. METHODS: Ten single-root teeth
      were embedded in an alginate mold. The foramina were widened from 0.6 mm to 1.0
      mm. The measurements were taken with all possible file sizes >=#10. The
      statistical accuracy of the Root ZX was calculated for the different diameters
      and for the influence of file size. RESULTS: The accuracy of the Root ZX apex
      locator with a range of error of +/-0.5 mm was 87% in an apical foramen size of
      0.6 mm and 84% using files size 45 or larger in an apical foramen size of 0.7 mm.
      With a tolerance of +/-1 mm, the accuracy was 99% in an apical foramen size of
      0.6 mm, 98% using files size 45 or larger in an apical foramen size of 0.7 mm,
      and 95% using files size 70 or larger in an apical foramen size of 0.8 mm. In the
      rest, accuracy was not certain. The measurements taken with smaller files were
      shorter. There were no cases of overestimation of the working length.
      CONCLUSIONS: The Root ZX apex locator was accurate for an apical size of 0.6 mm,
      independently of the file size; between 0.7 to 0.8 mm, we should adjust the files
      to the foramen, whereas above size 0.9 mm the locator is not accurate. The
      results show that the accuracy of this electronic apex locator is gradually lost
      as the foramen widens. Considering the stable conditions of in vitro studies, our
      findings advise caution in clinical application of the locator.

PMID- 21846556
TI  - Influence of chlorhexidine and ethanol on the bond strength and durability of the
      adhesion of the fiber posts to root dentin using a total etching adhesive system.
AB  - INTRODUCTION: The aim of this study was to investigate the effects of
      pretreatment of gel chlorhexidine (CHX) and ethanol (EtOH) on the bond strength
      and durability of the adhesion of the fiber post relined with resin composite to
      the root dentin using a total etch adhesive system. METHODS: Forty bovine incisor
      roots were divided into four groups after phosphoric acid etching: irrigation
      with physiologic solution (control), 5 minutes with CHX, 1 minute with EtOH, and
      5 minutes with chlorhexidine followed by 1 minute with EtOH. Fiber posts relined
      with resin composite were cemented with either RelyX ARC (3M ESPE, St Paul, MN)
      and a total etch adhesive system Scotchbond Multi-Purpose (3M ESPE). Each group
      was randomly divided into two subgroups: 24 hours of storage and 12 months of
      storage. All roots were sectioned transversely, and the push-out test was
      performed. Failure modes were observed, and the bond strength means were analyzed
      by analysis of variance and the Tukey test (alpha = 0.05). RESULTS: CHX
      irrigation resulted in homogeneous bond strength values at 24 hours and 12 months
      of storage (P < .05). A significant bond strength decrease was noticed after 12
      months of storage when irrigations were performed with physiologic solution and
      EtOH application only or associated with CHX (P < .05). CONCLUSIONS: The use of
      CHX pretreatment could preserve the bond strength of the fiber post relined with
      resin composite to root dentin for 12 months. The use of EtOH and CHX followed by
      EtOH did not preserve the bond strength of the total etch adhesive system
      Scotchbond Multi-Purpose.

PMID- 21846557
TI  - Penetration of Epiphany, Epiphany self-etch, and AH Plus into dentinal tubules: a
      scanning electron microscopy study.
AB  - INTRODUCTION: The purpose of this study was to measure the average depth of
      dentinal tubule sealer penetration in the middle third of teeth obturated with
      gutta-percha/AH Plus (Dentsply, DeTrey, Konstanz, Germany), Resilon/Epiphany
      (Pentron Clinical Technologies, Wallingford, CT), and Resilon/Epiphany self-etch
      (SE) using scanning electron microscopy (SEM). METHODS: The root canals of 36
      extracted single-rooted human teeth were prepared and randomly divided into three
      groups. Obturations were performed with the following filling materials using the
      lateral compaction technique: group 1, gutta-percha/AH Plus; group 2,
      Resilon/Epiphany; and group 3, Resilon/Epiphany SE. The specimens were prepared
      for SEM examination. The average depth of sealer penetration into the dentinal
      tubules was measured. Data were analyzed by one-way analysis of variance and a
      post hoc Tukey test. RESULTS: The mean (+/- standard deviation) values for the
      average depth of sealer penetration in the middle third of the roots were 22.07
      +/- 6.92 MUm, 31.56 +/- 6.80 MUm, and 21.50 +/- 9.25 MUm for AH Plus, Epiphany,
      and Epiphany SE, respectively. The average penetration depth of Epiphany was
      significantly higher than that of Epiphany SE and AH Plus (P < .05). There was no
      significant difference between the penetration depth of Epiphany SE and AH Plus
      (P > .05). CONCLUSIONS: It could be concluded that the average penetration for
      Epiphany into dentinal tubules within the middle third of the roots was
      significantly deeper than that of Epiphany SE and AH Plus.

PMID- 21846558
TI  - Expansive nasopalatine duct cysts with nasal involvement mimicking apical lesions
      of endodontic origin: a report of two cases.
AB  - INTRODUCTION: The nasopalatine duct cyst (NPDC) is the most frequent
      nonodontogenic cyst of the jaws and can be misinterpreted as an apical lesion of
      endodontic origin. METHODS: In the first case, a 17-year-old male patient was
      referred because of a pressure sensation in the anterior maxilla. The teeth #7,
      #8, #10, and #11 responded to cold sensitivity testing, and on tooth #9 an
      endodontic treatment had been performed 3 years ago. Only periapical radiographs
      had been taken, and a radicular cyst was suspected. In the second case, a 42-year
      old man reported inconvenience wearing his upper removable partial denture.
      Suspecting a jaw cyst in the anterior maxilla, the general dental practitioner
      referred the patient. RESULTS: Limited cone-beam computed tomography scans
      visualized the expansion of the cysts and the involvement of the neighboring
      structures in both cases. In both patients, the NPDCs were treated first by
      marsupialization in local anesthesia and second with cystectomy in general
      anesthesia with reconstruction of the defect areas with bone gained from the
      iliac crest. The final diagnosis was achieved by histopathological examination.
      CONCLUSIONS: If not diagnosed early, the NPDC can expand through the palatal
      and/or buccal cortical wall and also into the nasal cavity. The more expansive
      the NPDC is becoming, the more complex the final diagnosis is and the subsequent
      surgical therapy.

PMID- 21846559
TI  - Regenerative endodontic treatment (revascularization) of immature necrotic molars
      medicated with calcium hydroxide: a case series.
AB  - INTRODUCTION: Revascularization is an emerging regenerative treatment protocol
      with little published data available in immature molar teeth. The present case
      series demonstrates the outcome of revascularization treatment with intracanal
      medicament of calcium hydroxide in immature necrotic molars. METHODS: Immature
      necrotic permanent first molars (n = 6) of patients 8-11 years old were treated
      by a revascularization protocol that used 2.5% NaOCl irrigation, medication with
      calcium hydroxide placed in the coronal third of the root canals, induction of
      apical bleeding, and coronal sealing with white mineral trioxide aggregate. Among
      the treated teeth, 4 molars had undergone prior root canal instrumentation by the
      referring dentists. National Institutes of Health Image-J program with TurboReg
      plug-in was used for standardization of the radiographs and to determine the
      increase in root length and root width. RESULTS: After a follow-up period of 10
      months, all teeth demonstrated radiographic evidence of complete periapical
      healing, progressive thickening of dentinal walls, and continued apical
      development in the absence of clinical symptoms. Two uninstrumented molars showed
      a positive response to cold testing at 9 months. CONCLUSIONS: On the basis of a
      follow-up period of 10 months, the present cases demonstrate a favorable outcome
      of the revascularization procedure in immature necrotic molars by using calcium
      hydroxide medication in the coronal third of the root canals.

PMID- 21846560
TI  - Medication adherence in health care: are we utilizing what we have learned?

PMID- 21846561
TI  - Nucleic acid-mediated protein aggregation and assembly.
AB  - Amyloid proteins, mainly including amyloid-beta peptides, prion proteins, alpha
      synuclein, copper/zinc superoxide dismutase, as well as the bacterial protein
      RepA, are characterized by the deposition in a variety of tissues or cells as
      aggregated species (amyloids or insoluble deposits or inclusions) that share a
      distinctive beta-sheet-rich fibrillar ultrastructure. Although the amyloid is
      predominantly proteinaceous, careful examination of disease tissues and cells has
      revealed the presence of a significant quantity of polyanionic species including
      nucleic acids and polysaccharides associated with the amyloid. For example, in
      the brain tissues from victims of Alzheimer's disease, nucleic acids have been
      detected in neurofibrillary tangles and intracellular inclusions primarily
      composed of the tau protein, as well as in senile plaques composed of the amyloid
      beta peptides. Therefore, much effort has been directed to understanding the
      roles of the ubiquitous polyanionic species such as nucleic acids in the
      aggregation of amyloid proteins. Increasing evidence indicates that the amyloid
      proteins exhibit a high binding affinity for nucleic acids and the binding is
      mainly driven by electrostatic interactions between both. The association with
      nucleic acids leads to significant variations of the amyloid proteins in
      conformation. The nucleic acids have been observed to be capable of significantly
      inducing and accelerating the aggregation of amyloid proteins likely through a
      template effect. The template effect could restrict the orientations of amyloid
      proteins along nucleic acid strands and increase the local concentrations of
      amyloid proteins on nucleic acid surfaces, leading to enhancement in the
      intermolecular hydrophobic contacts of amyloid proteins. The nucleic acids have
      also been found to occur as an intrinsic or transient component in the resulted
      proteinaceous aggregates.

PMID- 21846562
TI  - Aggregation, stability, and formulation of human antibody therapeutics.
AB  - Many human monoclonal antibodies display poor biophysical properties, such as low
      stability and a propensity to aggregate. These unfavorable tendencies can be even
      more pronounced for human antibody fragments, which often require a considerable
      degree of optimization. In this review, we describe methods for analyzing
      aggregation and stability of human antibodies and antibody fragments. We also
      provide an overview of recent approaches to improve these properties through
      engineering and formulation.

PMID- 21846563
TI  - Lysozyme: a model protein for amyloid research.
AB  - Ever since lysozyme was discovered by Fleming in 1922, this protein has emerged
      as a model for investigations on protein structure and function. Over the years,
      several high-resolution structures have yielded a wealth of structural data on
      this protein. Extensive studies on folding of lysozyme have shown how different
      regions of this protein dynamically interact with one another. Data is also
      available from numerous biotechnological studies wherein lysozyme has been
      employed as a model protein for recovering active recombinant protein from
      inclusion bodies using small molecules like l-arginine. A variety of conditions
      have been developed in vitro to induce fibrillation in hen lysozyme. They include
      (a) acidic pH at elevated temperature, (b) concentrated solutions of ethanol, (c)
      moderate concentrations of guanidinium hydrochloride at moderate temperature, and
      (d) alkaline pH at room temperature. This review aims to bring together
      similarities and differences in aggregation mechanisms, morphology of aggregates,
      and related issues that arise using the different conditions mentioned above to
      improve our understanding. The alkaline pH condition (pH 12.2), discovered and
      studied extensively in our lab, shall receive special attention. More than a
      decade ago, it was revealed that mutations in human lysozyme can cause
      accumulation of large quantities of amyloid in liver, kidney, and other regions
      of gastrointestinal tract. Understanding the mechanism of lysozyme aggregation
      will probably have therapeutic implications for the treatment of systemic
      nonneuropathic amyloidosis. Numerous studies have begun to focus attention on
      inhibition of lysozyme aggregation using antibody or small molecules. The
      enzymatic activity of lysozyme presents a convenient handle to quantify the
      native population of lysozyme in a sample where aggregation has been inhibited.
      The rich information available on lysozyme coupled with the multiple conditions
      that have been successful in inducing/inhibiting its aggregation in vitro makes
      lysozyme an ideal model protein to investigate amyloidogenesis.

PMID- 21846564
TI  - Protein aggregation in a membrane environment.
AB  - Biological membranes are featured by a remarkable ability to modulate a wide
      range of physiological and pathological processes. Of these, protein aggregation
      is currently receiving the greatest attention, as one type of the ordered protein
      aggregates, amyloid fibrils, proved to be involved in molecular etiology of a
      number of fatal diseases. It has been hypothesized that nucleation of amyloid
      fibrils and toxic action of their precursors is mediated by lipid-protein
      interactions. Lipid bilayer provides a variety of environments in which
      aggregated state of polypeptide chain appears to be more thermodynamically
      favorable than its monomeric form. The major factors responsible for the enhanced
      self-association propensity of membrane-bound proteins include (i) structural
      transition of polypeptide chain into aggregation-prone conformation; (ii) protein
      crowding in a lipid phase; (iii) particular aggregation-favoring orientation and
      bilayer embedment of the protein molecules. All these factors are considered in
      the present review with an emphasis being put on the role of electrostatic,
      hydrophobic, and hydrogen-bonding phenomena in initiating and modulating the
      protein aggregation on a membrane template. Likewise, we survey the advanced
      experimental techniques employed for detection and structural characterization of
      the aggregated species in membrane systems.

PMID- 21846565
TI  - Contactins: structural aspects in relation to developmental functions in brain
      disease.
AB  - The contactins are members of a protein subfamily of neural immunoglobulin (Ig)
      domain-containing cell adhesion molecules. Their architecture is based on six N
      terminal Ig domains, four fibronectin type III domains, and a C-terminal
      glycophosphatidylinositol (GPI)-anchor to the extracellular part of the cell
      membrane. Genetics of neuropsychiatric disorders, particularly autism spectrum
      disorders, have pinpointed contactin-4, -5, and -6 (CNTN4, -5, and -6) as
      potential disease genes in neurodevelopmental disorders and suggested that they
      participate in pathways important for appropriate brain development. These
      contactins have distinct but overlapping patterns of brain expression, and null
      mutation causes subtle morphological and functional defects in the brain. The
      molecular basis of their neurodevelopmental functions is likely conferred by
      heterophilic protein interactions. Cntn4, -5, and -6 interact with protein
      tyrosine phosphatase receptor gamma (Ptptg) using a shared binding site that
      spans their second and third Ig repeats. Interactions with amyloid precursor
      protein (APP), Notch, and other IgCAMs have also been indicated. The present data
      indicate that Cntn4, -5, and -6 proteins may be part of heteromeric receptor
      complexes as well as serve as ligands themselves.

PMID- 21846566
TI  - Cellular RNA interference mechanisms. Preface.

PMID- 21846567
TI  - Epigenetic regulation of gene expression in human cells by noncoding RNAs.
AB  - Emerging evidence has begun to suggest that a vast array of noncoding RNAs is
      operative in human cells, with some containing the ability to directly modulate
      gene transcription. While observations of noncoding-RNA-based epigenetic
      regulation of gene expression were in the past relegated to imprinted or X-linked
      genes, it is now becoming apparent that several different genes in differentiated
      cells may be under some form of RNA-based regulatory control. Studies have begun
      to discern certain aspects of an underlying mechanism of action whereby noncoding
      RNAs modulate gene transcription. Much of the evidence suggests that noncoding
      RNAs are functional in controlling gene transcription by the targeted recruitment
      of epigenetic silencing complexes to homology-containing loci in the genome. The
      results of these studies, as well as the implications that a vast array of
      noncoding-RNA-based regulatory networks may be operative in human cells, are
      discussed. Knowledge of this emerging RNA-based epigenetic regulatory network has
      implications in cellular evolution as well as in an entirely new area of
      pharmacopeia.

PMID- 21846568
TI  - Small RNA-induced transcriptional gene regulation in mammals mechanisms,
      therapeutic applications, and scope within the genome.
AB  - Argonaute-bound small RNAs, derived from RNA interference and related pathways,
      are well-known effectors of posttranscriptional gene silencing (PTGS). Yet, these
      complexes also play an important role in affecting gene expression at the
      transcriptional level, either by transcriptional gene silencing (TGS) or
      activation (TGA). Our current understanding of how small RNAs are able to both
      activate and suppress transcription is unclear. In this review, we briefly
      outline the biogenesis of small RNAs and explore the mechanisms behind the
      various phenomena attributed to AGO-bound small RNA-mediated transcriptional
      regulation. The therapeutic potential of TGS and TGA is examined, emphasizing the
      distinct advantages over PTGS approaches with examples of application to cancer
      and diseases associated with viruses, aberrant splicing, and dysregulated
      heterochromatin. Finally, the influence of promoter architecture on gene
      susceptibility to transcriptional regulation is discussed in the light of how
      this impacts the scope of small RNA-induced transcriptional regulation within the
      genome.

PMID- 21846569
TI  - MicroRNA function in the nervous system.
AB  - MicroRNAs (miRNAs) are an extensive class of small noncoding RNAs that control
      posttranscriptional gene expression. miRNAs are highly expressed in neurons where
      they play key roles during neuronal differentiation, synaptogenesis, and
      plasticity. It is also becoming increasingly evident that miRNAs have a profound
      impact on higher cognitive functions and are involved in the etiology of several
      neurological diseases and disorders. In this chapter, we summarize our current
      knowledge of miRNA functions during neuronal development, physiology, and
      dysfunction.

PMID- 21846570
TI  - The role of microRNAs in viral infection.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that have emerged in recent
      years as central regulators of eukaryotic gene expression. In mammalian systems,
      miRNAs are associated with numerous pathological and physiological pathways.
      miRNAs are important in many viral infections, with different viral families
      expressing their own miRNAs, manipulating host miRNA expression, or showing
      direct or indirect regulation by host or viral miRNAs. In this chapter we will
      examine the current evidence for interplay between the miRNA pathway and viral
      infections in mammals.

PMID- 21846571
TI  - Toward a durable treatment of HIV-1 infection using RNA interference.
AB  - RNA interference (RNAi) is a cellular mechanism that mediates sequence-specific
      gene silencing at the posttranscriptional level. RNAi can be used as an antiviral
      approach against human pathogens. An attractive target for RNAi therapeutics is
      the human immunodeficiency virus type 1 (HIV-1), and the first clinical trial
      using a lentiviral gene therapy was initiated in early 2008. In this chapter, we
      focus on some basic principles of such an RNAi-based gene therapy against HIV-1.
      This includes the subjects of target site selection within the viral RNA genome,
      the phenomenon of viral escape, and therapeutic strategies to prevent viral
      escape. The latter antiescape strategies include diverse combinatorial RNAi
      approaches that are all directed against the HIV-1 RNA genome. As an alternative
      strategy, we also discuss the possibilities and restrictions of targeting
      cellular cofactors that are essential for virus replication, but less important
      for cell physiology.

PMID- 21846572
TI  - When cellular networks run out of control: global dysregulation of the RNAi
      machinery in human pathology and therapy.
AB  - RNA interference (RNAi) is an evolutionarily conserved fundamental cellular
      mechanism of potent gene and genome regulation whose misfunction is associated
      with numerous major human pathologies, from metabolic disorders and viral
      infections to cancers. Over the past 5 years, compelling evidence has been
      accumulated that this association is provided by dysregulations of specific
      mi(cro)RNAs and the ensuing aberrant expression of their target genes. Moreover,
      a string of interesting reports has now added proof that human disorders are also
      frequently characterized by global alterations in the RNAi machinery, comprising
      irregular expression and function of the key protein players Drosha, DGCR8,
      Exportin-5, Dicer, TRBP, and Argonaute. Here, we comprehensively review these
      emerging findings in the specific contexts of cancers and infections with viral
      pathogens and, in addition, describe related observations in preclinical
      gene/RNAi therapy studies. Finally, we also thoroughly discuss the relevance of
      these results for future basic RNAi research as well as for the looming clinical
      translation of RNAi-based technologies and therapeutic concepts.

PMID- 21846573
TI  - Association between genetic risk score and periodontitis onset and progression: a
      pilot study.
AB  - AIM: Recent research has focused attention on the single nucleotide polymorphisms
      (SNPs) involved in the host response in periodontitis. However, so as to combine
      the relatively small effects of individual genes the use of multi locus genetic
      risk (GRS) has been proposed. This study aims to evaluate whether the genetic
      risk score may predict periodontitis onset and progression. MATERIALS AND
      METHODS: Fifty patients were divided into various groups according to periodontal
      status. Total DNA was isolated from epithelial oral cells by a masked operator
      and the selected SNPs were analysed. A GRS was calculated using an additive
      model. RESULTS: We found a strong association only between TNF rs1800629 and
      diffused forms of periodontitis. Data show that GRS is able to discriminate
      diffused forms of periodontitis from localized ones. Finally, a progressive
      increase of the GRS is evident in advanced periodontitis in comparison with early
      forms. DISCUSSION: In recent years, research on genetic polymorphism has had
      limited success in predicting the susceptibility to periodontal disease. However,
      our results indicate that the use of the genetic risk score could be promising.
      Further studies are necessary to include data from multiple genes so as to
      confirm our result.

PMID- 21846574
TI  - Early stage ovarian cancers: angiogenesis inhibition and clear cell cancers.

PMID- 21846575
TI  - Minimum amount of physical activity for reduced mortality and extended life
      expectancy: a prospective cohort study.
AB  - BACKGROUND: The health benefits of leisure-time physical activity are well known,
      but whether less exercise than the recommended 150 min a week can have life
      expectancy benefits is unclear. We assessed the health benefits of a range of
      volumes of physical activity in a Taiwanese population. METHODS: In this
      prospective cohort study, 416,175 individuals (199,265 men and 216,910 women)
      participated in a standard medical screening programme in Taiwan between 1996 and
      2008, with an average follow-up of 8.05 years (SD 4.21). On the basis of the
      amount of weekly exercise indicated in a self-administered questionnaire,
      participants were placed into one of five categories of exercise volumes:
      inactive, or low, medium, high, or very high activity. We calculated hazard
      ratios (HR) for mortality risks for every group compared with the inactive group,
      and calculated life expectancy for every group. FINDINGS: Compared with
      individuals in the inactive group, those in the low-volume activity group, who
      exercised for an average of 92 min per week (95% CI 71-112) or 15 min a day (SD
      1.8), had a 14% reduced risk of all-cause mortality (0.86, 0.81-0.91), and had a
      3 year longer life expectancy. Every additional 15 min of daily exercise beyond
      the minimum amount of 15 min a day further reduced all-cause mortality by 4% (95%
      CI 2.5-7.0) and all-cancer mortality by 1% (0.3-4.5). These benefits were
      applicable to all age groups and both sexes, and to those with cardiovascular
      disease risks. Individuals who were inactive had a 17% (HR 1.17, 95% CI 1.10
      1.24) increased risk of mortality compared with individuals in the low-volume
      group. INTERPRETATION: 15 min a day or 90 min a week of moderate-intensity
      exercise might be of benefit, even for individuals at risk of cardiovascular
      disease. FUNDING: Taiwan Department of Health Clinical Trial and Research Center
      of Excellence and National Health Research Institutes.

PMID- 21846576
TI  - Survival benefit associated with low-level physical activity.

PMID- 21846578
TI  - Minor physical anomalies in patients with bipolar I disorder and normal controls.
AB  - BACKGROUND: The neurodevelopmental hypothesis is well established in
      schizophrenia but has received modest empirical support in bipolar disorder. In
      schizophrenia it is partly based on the higher prevalence of minor physical
      anomalies (MPAs), established by many well controlled studies. No studies with
      comparable designs have been performed in bipolar disorder. The present study
      aims to establish the rate and topographic distribution of MPAs in bipolar I
      patients. METHODS: The subjects were 61 patients (25 men, 36 women) with bipolar
      I disorder and 103 normal subjects (49 men, 54 women) who were examined for MPAs
      using a modified version of the Waldrop Physical Anomaly Scale. RESULTS: The
      bipolar I patients showed significantly higher regional MPA scores in 3 distinct
      regions - mouth, feet and head, as well as in the overall scores for the
      craniofacial complex, the periphery and the total MPA score. Differences were
      statistically significant for 3 anomalies - high/steepled palate, big gap between
      I and II toes and furrowed tongue that made significant contribution to the
      prediction of the patient-control status in a discriminant analysis model.
      CONCLUSIONS: Our data suggest that aberrant processes of neurodevelopment may
      contribute to the etiology of bipolar I disorder. The field is open for further
      research using modern instruments and designs in order to identify potential
      biological markers for bipolar disorder.

PMID- 21846577
TI  - Expression of liquoral neuroprotection markers in children with acute
      lymphoblastic leukemia.
AB  - Brain damage related to intrathecal methotrexate in children with acute
      lymphoblastic leukemia (ALL) is still unclear. Neuroinflammatory mechanisms and
      intracerebral production of specific biomarkers, play a key role in determining
      neuroprotective mechanisms after brain injury. To determine whether the CSF
      concentrations of neuron-specific enolase (NSE), neurotrophic factors and
      doublecortin (DCX) are influenced by repeated intrathecal methotrexate
      administrations, we prospectively collected CSF samples from 10 children with ALL
      and 10 controls. Our results showed an increased expression of the liquoral
      markers. This up-regulation could be interpreted as a neuroprotective response of
      the brain against the neuronal damages induced by MTX.

PMID- 21846579
TI  - Prevention of facial injuries in unmounted equestrians.

PMID- 21846580
TI  - A review of parasitic zoonoses in a changing Southeast Asia.
AB  - Parasitic zoonoses are common and widely distributed in the Southeast Asian
      region. However, the interactions between parasites, hosts and vectors are
      influenced by environmental, socio-cultural and livestock production changes that
      impact on the distribution, prevalence and severity of disease. In this review we
      provide an update on new knowledge in the context of ongoing changes for the food
      borne pig associated zoonoses Taenia solium and Trichinella spp., the food-borne
      trematodes Opisthorchis viverrini and Clonorchis sinensis, the water-borne
      trematodes Schistosoma spp., the vector-borne zoonotic protozoa Plasmodium
      knowlesi and Leishmania spp. and the soil-borne zoonotic hookworm Ancylostoma
      ceylanicum. These various changes need to be considered when assessing or
      developing regional control programs or devising new research initiatives in a
      changing SE Asia.

PMID- 21846581
TI  - Efficacy of methanolic extract of Balanites aegyptiaca fruits on Toxocara
      vitulorum.
AB  - In this study, the effect of the methanolic extract of Balanites aegyptiaca
      fruits (BAE) on adult Toxocara vitulorum was evaluated after incubating the
      parasites in Ringer solution containing 10, 30, 60, 120 and 240 MUg/ml of the
      methanolic extract, for 24h using light and scanning electron microscopic
      observations. Differences in response to BAE action were concentration dependent.
      These changes occurred in definite sequences in response to BAE concentration and
      were consisted of slightly swelling which became pronounced and so severe, with
      lips showed wrinkled cuticular surface and deformed sensory papillae on
      increasing the BAE concentration. The strongest effects were reached with the
      highest BAE concentration, where disorganization of the cuticle and body
      musculature was observed. Additionally, the ovicidal effect of BAE, at the
      previous concentrations, on the development of T. vitulorum eggs was examined
      after 12h exposure. The inhibitory activity of BAE on egg development was
      concentration dependent and the highest value reached to 100% with the
      concentration of 240 MUg/ml. These results were compared with those observed in
      the worm cuticle and eggs following incubation in albendazole, as it was a broad
      spectrum nematodicidal compound with well-known ovicidal activity.

PMID- 21846582
TI  - Protection in a hamster model of congenital toxoplasmosis.
AB  - Almost uniform protection against congenital toxoplasmosis initiated by
      inoculations with cysts and oocysts of the parasite was seen in the hamster
      model, among strains of different genotypes. Because the RH immunization prior to
      pregnancy has to be controlled with medication for most of the hamsters to
      survive, and also some congenital transmission of Toxoplasma was observed during
      the chronic stage of the infection, the hamster is considered less practical than
      the rat and the BALB/c mouse models. It is concluded that the hamster model
      closely resembles protection against congenital infection in nature, where most
      of the pregnant women and ewes that experienced a toxoplasma infection
      previously, protect their fetuses against an infection with the parasite during
      pregnancy.

PMID- 21846583
TI  - Comparison of diagnostic methods to detect piroplasms in asymptomatic cattle.
AB  - This study was carried out to compare different diagnostic techniques to reveal
      the presence of piroplasms in asymptomatic cattle kept at pasture. Nineteen blood
      samples were collected from animals of two different areas of Emilia Romagna
      Region of Italy and processed for microscopic observation, PCR, serological test
      (IFAT) for Babesia bovis and Babesia bigemina antibodies and in vitro
      cultivation. The cultures were performed on both bovine and ovine erythrocytes.
      Seventeen blood smears (89%) were positive for piroplasms, while PCR was positive
      on 18 samples (95%). DNA sequencing of 18S rRNA identified the piroplasms as
      Theileria spp. In vitro cultures were successful for 6 samples (32%) cultured on
      bovine blood and subsequent identified these as Babesia major by PCR. On IFAT
      analyses of 16 samples, 36.8% resulted positive for B. bovis and 31.6% positive
      for B. bigemina. These results show, in the same animals, the co-infection with
      Babesia spp. and Theileria spp.; the detection of B. major was possible only
      using the in vitro cultures.

PMID- 21846584
TI  - Cytokine gene expression profiles in peripheral blood mononuclear cells from
      Neospora caninum naturally infected dams throughout gestation.
AB  - Neospora caninum is a major cause of abortion in cattle but it is not known why
      some infected animals suffer abortion while others do not. An essential role in
      protective immunity against N. caninum has been proposed for Th1 cytokines such
      as IFN-gamma and IL-12 although cytokine patterns in N. caninum infected pregnant
      cattle have been scarcely addressed. In this study, gene expression of the
      cytokines IFN-gamma, IL-12, IL-10, IL-4 and TNF-alpha was analyzed by real time
      RT-PCR in peripheral blood mononuclear cells in N. caninum naturally infected
      dams throughout pregnancy. Blood samples were drawn from 18 cows (13 N. caninum
      seropositive and 5 N. caninum seronegative) on Days 45, 90, 120, 150, 180 and 210
      of pregnancy or until abortion. Four seropositive animals aborted. Compared to
      the seronegative animals, N. caninum infected dams showed up-regulated mRNA
      levels of the Th1 cytokines, IFN-gamma, TNF-alpha and IL-12p40, along with up
      regulation of the T regulatory (Treg) cytokine IL-10. In contrast, expression
      levels of IL-4 (Th2 cytokine) did not differ significantly among the different
      groups throughout the study period. Our findings indicate clear differences in
      peripheral blood cytokine gene expression levels during pregnancy between animals
      naturally infected with N. caninum and seronegative control animals. To the best
      of our knowledge, this is the first study to examine the gene expression of Th1,
      Th2 and regulatory cytokines in the peripheral blood of pregnant cows naturally
      infected with N. caninum.

PMID- 21846585
TI  - Prevalence of selected zoonotic and vector-borne agents in dogs and cats in Costa
      Rica.
AB  - To estimate the prevalence of enteric parasites and selected vector-borne agents
      of dogs and cats in San Isidro de El General, Costa Rica, fecal and serum samples
      were collected from animals voluntarily undergoing sterilization. Each fecal
      sample was examined for parasites by microscopic examination after fecal
      flotation and for Giardia and Cryptosporidium using an immunofluorescence assay
      (IFA). Giardia and Cryptosporidium IFA positive samples were genotyped after PCR
      amplification of specific DNA if possible. The seroprevalence rates for the
      vector-borne agents (Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia canis,
      and Anaplasma phagocytophilum) were estimated based on results from a
      commercially available ELISA. Enteric parasites were detected in samples from 75%
      of the dogs; Ancylostoma caninum, Trichuris vulpis, Giardia, and Toxocara canis
      were detected. Of the cats, 67.5% harbored Giardia spp., Cryptosporidium spp.,
      Ancylostoma tubaeforme, or Toxocara cati. Both Cryptosporidium spp. isolates that
      could be sequenced were Cryptosporidium parvum (one dog isolate and one cat
      isolate). Of the Giardia spp. isolates that were successfully sequenced, the 2
      cat isolates were assemblage A and the 2 dog isolates were assemblage D. D.
      immitis antigen and E. canis antibodies were identified in 2.3% and 3.5% of the
      serum samples, respectively. The prevalence of enteric zoonotic parasites in San
      Isidro de El General in Costa Rica is high in companion animals and this
      information should be used to mitigate public health risks.

PMID- 21846586
TI  - Liquid crystal-based sensors for the detection of heavy metals using surface
      immobilized urease.
AB  - In this study, a new method for the detection of heavy metals in aqueous phase
      was developed using liquid crystals (LCs). When UV-treated nematic LC, 4-cyano-4'
      pentyl biphenyl (5CB) that was confined in the urease-modified gold grid was
      immersed in a urea solution, an optical response from bright to dark was observed
      under a polarized microscope, indicating that a planar-to-homeotropic
      orientational transition of the LC occurred at the aqueous/LC interface. Since
      urease hydrolyzes urea to produce ammonia, which would be ionized into ammonium
      and hydroxide ions, the main product of the photochemically degraded 5CB, 4-cyano
      4'-biphenylcarboxylic acid (CBA), was deprotonated and self-assembled at the
      interface, inducing the orientational transition in the LC. Due to the high
      sensitivity and rapid response of this system, detection of heavy metal ions was
      further exploited. The divalent copper ion, which could effectively inhibit the
      activity of urease, was used as a model heavy metal ion. The optical appearance
      of the LC did not change when urea was in contact with the copper nitrate hydrate
      blocked urease. After the copper-inhibited urease was reactivated by EDTA, a
      bright-to-dark shift in the optical signal was regenerated, indicating an
      orientational transition of the LC. This type of LC-based sensor shows high
      spatial resolution due to its optical characteristics and therefore could
      potentially be used to accurately monitor the presence of enzyme inhibitors such
      as heavy metal ions in real-time.

PMID- 21846587
TI  - Immunodevice for simultaneous detection of two relevant tumor markers based on
      separation of different microparticles by dielectrophoresis.
AB  - In this study, a rapid immunosensing system has been developed for simultaneous
      analysis of two tumor markers, alpha-fetoprotein (AFP) and prostate-specific
      antigen (PSA). The strategy for rapid multisensing is based on rapid
      immunoreactions occurring on the surface of microparticles and the spatial
      separation of different particles that exhibit distinct dielectrophoretic (DEP)
      properties. Recognition events for immunoreactions have been performed on the
      surfaces of two different microparticles conjugated with two different
      antibodies: polystyrene (PS) microparticles with an anti-AFP antibody and gold
      coated (50 nm) PS microparticles with an anti-PSA antibody. The DEP devices
      consisted of an upper indium tin oxide (ITO) glass and a lower ITO electrode with
      a castellated structure. Sandwich structured immunocomplexes of AFP and PSA were
      created on the microparticles and then labeled with fluorescent molecules via a
      secondary antibody. After introducing the particles into the DEP devices, an
      alternating current (AC) voltage (20 V peak-to-peak voltage and 30 kHz) was
      applied between the upper ITO and lower electrodes to manipulate the particles
      with negative dielectrophoresis (n-DEP).The uncoated PS particles and the gold
      coated PS particles rapidly moved and separated to form wave-like line and
      triangular aggregates, respectively. The measurements of the fluorescence signals
      from the uncoated and gold-coated PS particles directed to different regions of
      the DEP device permit the determination of the concentrations of AFP and PSA
      simultaneously. No cross-reactivity was observed for either of the
      immunorecognition events. Limits of detection achieved for the AFP and PSA assays
      were 0.18 and 1.1 ng mL(-1), respectively, which satisfy medical requirements for
      both antigens in human serum. The total assay time required for the simultaneous
      detection of the two different analytes in this study (25 min) was shortened
      compared to the conventional enzyme-linked immunosorbent assay.

PMID- 21846588
TI  - Does preoperative anxiety and depression predict satisfaction after total knee
      replacement?
AB  - BACKGROUND AND PURPOSE: Approximately one fifth of patients are not satisfied
      with the outcome of total knee arthroplasty (TKA). Preoperative variables
      associated with poorer outcomes are severity and chronicity of pain,
      psychological disease, poor coping strategies and pain catastrophisation.
      Psychological disease may be expressed as anxiety and depression. It is unclear
      whether anxiety and depression before TKA are constitutional or result from knee
      pain. The aim of this study was to explore the association of anxiety and
      depression with knee pain and function using specific outcome measures. METHODS:
      Forty consecutive patients undergoing TKA completed Hospital Anxiety and
      Depression Scale (HAD) and Oxford Knee Scores (OKS) preoperatively and at 3 and 6
      months postoperatively. RESULTS: The HAD and OKS significantly improved post
      operatively (p<0.001). There was a greater change between the preoperative and
      postoperative scores in the OKS than the HAD. The severity of preoperative
      anxiety and depression was associated with higher levels of knee disability
      (coefficient -0.409, p=0.009). Postoperatively reduction in anxiety and
      depression was associated with improvement in knee disability after 3
      (coefficient -0.459, p=0.003) and 6 months (coefficient -0.428, p=0.006).
      INTERPRETATION: The difficulty in interpreting preoperative anxiety and
      depression and the outcome of TKA is establishing whether they are the cause or
      effect of pain in the knee. As anxiety and depression improve with knee pain and
      function, this study suggests that knee pain contributes to the psychological
      symptoms and that a successful TKA offers an excellent chance of improving both.

PMID- 21846589
TI  - A historical view from thirty eventful years of immunotherapy in autoimmune
      diabetes.
AB  - Type 1 diabetes is an autoimmune disease. It was thus logical to attempt
      preventing or stopping the progression of the disease by immunotherapy. Following
      the strategies used in organ transplantation, the first trials in the 80s used
      cyclosporin in patients presenting recently diagnosed Type 1 diabetes. The effect
      was spectacular but waned when the treatment was stopped as the effect was non
      antigen-specific. Going back from bed to bench-side major efforts were then
      devoted to device strategies allowing induction or restoration of self-tolerance.
      Two major approaches provided encouraging results when used in spontaneous models
      of autoimmune diabetes that are the use of beta-cell autoantigens and of
      monoclonal antibodies to CD3. Based on these results academic phase II trials and
      subsequently pharmaceutically driven phase III trials were launched. Results are
      now available and when critically analyzed in the frame of these last three
      decades they provide support to the possibility of making step by step
      immunotherapy available to all new onset diabetic patients with a hope of
      inducing long-term remission of the disease if the treatment is started
      sufficiently early, immediately after diagnosis.

PMID- 21846590
TI  - Increased superoxide accumulation in pyruvate dehydrogenase complex deficient
      fibroblasts.
AB  - The pyruvate dehydrogenase complex (PDC) oxidizes pyruvate to acetyl CoA and is
      critically important in maintaining normal cellular energy homeostasis. Loss-of
      function mutations in PDC give rise to congenital lactic acidosis and to
      progressive cellular energy failure. However, the subsequent biochemical
      consequences of PDC deficiency that may contribute to the clinical manifestations
      of the disorder are poorly understood. We postulated that altered flux through
      PDC would disrupt mitochondrial electron transport, resulting in oxidative
      stress. Compared to cells from 4 healthy subjects, primary cultures of skin
      fibroblasts from 9 patients with variable mutations in the gene encoding the
      alpha subunit (E1alpha) of pyruvate dehydrogenase (PDA1) demonstrated reduced
      growth and viability. Superoxide (O(2)(.-)) from the Qo site of complex III of
      the electron transport chain accumulated in these cells and was associated with
      decreased activity of manganese superoxide dismutase. The expression of
      uncoupling protein 2 was also decreased in patient cells, but there were no
      significant changes in the expression of cellular markers of protein or DNA
      oxidative damage. The expression of hypoxia transcription factor 1 alpha
      (HIF1alpha) also increased in PDC deficient fibroblasts. We conclude that PDC
      deficiency is associated with an increase in O(2)(.-) accumulation coupled to a
      decrease in mechanisms responsible for its removal. Increased HIF1alpha
      expression may contribute to the increase in glycolytic flux and lactate
      production in PDC deficiency and, by trans-activating pyruvate dehydrogenase
      kinase, may further suppress residual PDC activity through phosphorylation of the
      E1alpha subunit.

PMID- 21846591
TI  - Device-associated infection rates in 398 intensive care units in Shanghai, China:
      International Nosocomial Infection Control Consortium (INICC) findings.
AB  - OBJECTIVES: To determine device-associated healthcare-associated infection (DA
      HAI) rates and the microorganism profile in 398 intensive care units (ICUs) of 70
      hospitals in Shanghai, China. METHODS: An open-label, prospective, cohort, active
      DA-HAI surveillance study was conducted on patients admitted to 398 tertiary-care
      ICUs in China from September 2004 to December 2009, implementing the methodology
      developed by the International Nosocomial Infection Control Consortium (INICC).
      The data were collected in the participating ICUs, and uploaded and analyzed at
      the INICC headquarters on proprietary software. DA-HAI rates were registered by
      applying the definitions of the US Centers for Disease Control and Prevention
      (CDC) National Healthcare Safety Network (NHSN). We analyzed the rates of DAI
      HAI, ventilator-associated pneumonia (VAP), central line-associated bloodstream
      infection (CLABSI), and catheter-associated urinary tract infection (CAUTI), and
      their microorganism profiles. RESULTS: During the 5 years and 4 months of the
      study, 391 527 patients hospitalized in an ICU for an aggregate of 3,245,244
      days, acquired 20,866 DA-HAIs, an overall rate of 5.3% (95% confidence interval
      (CI) 5.3-5.4) and 6.4 (95% CI 6.3-6.5) infections per 1000 ICU-days. VAP posed
      the greatest risk (20.8 per 1000 ventilator-days, 95% CI 20.4-21.1), followed by
      CAUTI (6.4 per 1000 catheter-days, 95% CI 6.3-6.6) and CLABSI (3.1 per 1000
      catheter-days, 95% CI 3.0-3.2). The most common isolated microorganism was
      Acinetobacter baumannii (19.1%), followed by Pseudomonas aeruginosa (17.2%),
      Klebsiella pneumoniae (11.9%), and Staphylococcus aureus (11.9%). CONCLUSIONS: DA
      HAIs in the ICUs of Shanghai pose a far greater threat to patient safety than in
      ICUs in the USA. This is particularly the case for the VAP rate, which is much
      higher than the rates found in developed countries. Active infection control
      programs that carry out infection surveillance and implement prevention
      guidelines can improve patient safety and must become a priority.

PMID- 21846593
TI  - Tests for prediction of active tuberculosis.

PMID- 21846594
TI  - Recent decline in the U.S. death rate from myeloproliferative neoplasms, 1999
      2006.
AB  - BACKGROUND: Myeloproliferative neoplasms (MPNs) are classified as neoplasms of
      uncertain or unknown behavior in the International Classification of Diseases
      (ICD) Version 10 and can contribute to risk of death from complications
      (especially thrombosis). METHODS: U.S age-standardized death rates using ICD
      Version 10 codes relevant to classical MPN (i.e., polycythemia vera, essential
      thrombocythemia, and "chronic myeloproliferative disease") were examined for 1999
      2006. The underlying cause of death and also all causes ("multiple causes" or
      "mentions") coded on death certificates were considered. Trends were assessed by
      using percentage change (PC) in rate between 1999 and 2006, and annual percentage
      change (APC) estimated from linear regression. RESULTS: The decline in death
      rates was large for MPN, whether based only the underlying cause (PC=-19.7%, APC=
      3.4%) or on the substantially higher rates based on any cause (PC=-24.1%, APC=
      3.8%), and was consistent by gender and age group (<65 and 65+ years). For deaths
      with MPN coded as other than the underlying cause, cardiovascular diseases were
      the most common underlying cause and the ASR for these deaths declined
      substantially (PC=-40.0%). CONCLUSIONS: Use of the underlying cause of death in
      surveillance will considerably underestimate MPN-related mortality rates in the
      population. Studies are needed on treatment in random samples of MPN patients
      from population-based cancer registries. Continued surveillance of MPN-related
      mortality rates in the population is needed in view of recent attempts (including
      the use of aspirin) to control cardiovascular complications of MPN.

PMID- 21846592
TI  - Predictive value of interferon-gamma release assays for incident active
      tuberculosis: a systematic review and meta-analysis.
AB  - BACKGROUND: We aimed to assess whether interferon-gamma release assays (IGRAs)
      can predict the development of active tuberculosis and whether the predictive
      ability of these tests is better than that of the tuberculin skin test (TST).
      METHODS: Longitudinal studies of the predictive value for active tuberculosis of
      in-house or commercial IGRAs were identified through searches of PubMed, Embase,
      Biosis, and Web of Science and complementary manual searches up to June 30, 2011.
      Eligible studies included adults or children, with or without HIV, who were free
      of active tuberculosis at study baseline. We summarised incidence rates in forest
      plots and pooled data with random-effects models when appropriate. We calculated
      incidence rate ratios (IRR) for rates of disease progression in IGRA-positive
      versus IGRA-negative individuals. FINDINGS: 15 studies had a combined sample size
      of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4
      years (IQR 2-6), even in IGRA-positive individuals, was 4-48 cases per 1000
      person-years. Seven studies with no possibility of incorporation bias and
      reporting baseline stratification on the basis of IGRA results showed a moderate
      association between positive results and subsequent tuberculosis (pooled
      unadjusted IRR 2.10, 95% CI 1.42-3.08). Compared with test-negative results, IGRA
      positive and TST-positive results were much the same with regard to the risk of
      tuberculosis (pooled IRR in the five studies that used both was 2.11 [95% CI 1.29
      3.46] for IGRA vs 1.60 [0.94-2.72] for TST at the 10 mm cutoff). However, the
      proportion of IGRA-positive individuals in seven of 11 studies that assessed both
      IGRAs and TST was generally lower than TST-positive individuals. INTERPRETATION:
      Neither IGRAs nor the TST have high accuracy for the prediction of active
      tuberculosis, although use of IGRAs in some populations might reduce the number
      of people considered for preventive treatment. Until more predictive biomarkers
      are identified, existing tests for latent tuberculosis infection should be chosen
      on the basis of relative specificity in different populations, logistics, cost,
      and patients' preferences rather than on predictive ability alone. FUNDING:
      Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome
      Trust, Canadian Institutes of Health Research, UK Medical Research Council, and
      the European and Developing Countries Clinical Trials Partnership.

PMID- 21846595
TI  - Perinatal risk factors for childhood testicular germ-cell cancer: a Nordic
      population-based study.
AB  - INTRODUCTION: In contrast to research in adults, there have been limited studies
      on testicular germ-cell cancer among boys aged <15 years. The aim of the study
      was to investigate the association between perinatal characteristics and
      childhood testicular germ-cell cancer. METHODS: We identified 152 patients with
      childhood germ-cell cancer among boys (<15 years) born in Norway, Sweden, Finland
      and Denmark between 1967 and 2006 using the cancer and medical birth registries.
      For each case we sampled 10 population controls matched on year and country of
      birth. We used conditional logistic regression analysis to estimate odds ratios
      for cancer risk. RESULTS: There was a weak, positive association between high
      (>=4000 g) birth weight and childhood testicular germ-cell cancer (adjusted
      OR=1.25; 95% CI: 0.83-1.90) compared with normal birth weight, and a
      correspondingly elevated risk for low birth weight (adjusted OR=1.41; 95% CI:
      0.43-4.56). For Ponderal Index (PI) there was an increased risk for low and high
      values compared to those in the middle category (adjusted OR=1.64; 95% CI: 1.03
      2.62 and 1.67; 95% CI: 0.93-2.99), respectively. There was no association between
      birth length and childhood testicular germ-cell cancer. The adjusted OR for
      testicular cancer among first born was 1.40; 95% CI: 0.96-2.05. Greater maternal
      age and less maternal education appeared to increase the risk, but the estimates
      were not statistically significant. CONCLUSION: We found a U-shaped association
      between fetal growth, measured as the PI, and childhood testicular germ-cell
      cancer. Our findings support the notion that abnormal fetal growth rate confers a
      risk in pediatric testicular cancer [corrected].

PMID- 21846597
TI  - Time trends and age-period-cohort analyses on incidence rates of nasopharyngeal
      carcinoma during 1993-2007 in Wuhan, China.
AB  - BACKGROUND: Declines in incidence rates of nasopharyngeal carcinoma (NPC) were
      observed in Hong Kong and Taiwan but not other high-risk regions in China, while
      evidences from low-risk regions in China are still lacking. This study aimed to
      examine the time trends (1993-2007) of NPC in Wuhan (a low-risk region) and
      assess the birth cohort and calendar period effects on the observed temporal
      trends. METHOD: Using data from Wuhan Cancer Registry, age-standardized annual
      incidence rates of NPC were calculated by the direct method using the WHO World
      Standard Population (2000) as the reference. Trend in incidence rates of NPC
      during 1993-2007 was evaluated. Age-period-cohort models were also applied to
      assess the effects of age, calendar time and birth cohort on the observed
      temporal trends. RESULTS: A total of 1685 new NPC cases (1210 males and 475
      females) were diagnosed during 1993-2007 in Wuhan. The annual percentage change
      in incidence rates of NPC were 0.15% (95% confidence interval: -3.88% to 4.34%)
      for males and -1.17% (95% confidence interval: -4.85% to 2.66%) for females. No
      obvious cohort or period effect on the incidence rates of NPC was observed.
      CONCLUSION: The incidence rates of NPC remained stable during 1993-2007 in Wuhan,
      a low-risk region in China.

PMID- 21846598
TI  - Bayesian population modeling of phase I dose escalation studies: Gaussian process
      versus parametric approaches.
AB  - The early stages of the drug development process are often characterized by a
      limited number of subjects participating the study and a limited number of
      measurements per individual that can be collected, mainly due to technical,
      ethical, and cost reasons. The so-called dose escalation studies, performed
      during phase I, usually involve about 40 subjects or less, and feature
      observations at no more than three (rarely four or five) dose levels-per-subject.
      Depending on the complexity of the underlying pharmacokinetics, simple linear
      models or nonlinear ones (e.g., power, E(max) models) may be appropriate to
      describe the relationship between the metrics of systemic exposure to the drug
      (C(max), AUC) and the administered dose. However, in such data-poor scenarios,
      formulating models based on parametric descriptions is generally hard, and may
      easily result in model misspecification. Hence, nonparametric or "model-free"
      solutions, borrowed from the machine learning field, are deemed appealing. We
      resort to Gaussian process theory to work out Bayesian posterior expectations of
      a population (a.k.a mixed-effects) regression problem, namely Population
      Smoothing Splines (PSS). We show that in seven experimental dose escalation
      studies, Population Smoothing Splines improve on three widely used parametric
      population methods. Superiority of the model-free technique is confirmed by a
      simulated benchmark: Population Smoothing Splines compare very favorably even
      with the true parametric model structure underlying the simulated data.

PMID- 21846596
TI  - Risk factors for esophageal and gastric cancers in Shanxi Province, China: a case
      control study.
AB  - OBJECTIVE: Smoking and alcohol consumption explain little of the risk for upper
      gastrointestinal (UGI) cancer in China, where over half of all cases in the world
      occur. METHODS: We evaluated questionnaire-based risk factors for UGI cancers in
      a case-control study from Shanxi Province, China, including 600 esophageal
      squamous cell carcinomas (ESCCs), 599 gastric cardia adenocarcinomas (GCAs), 316
      gastric noncardia adenocarcinomas (GNCAs), and 1514 age- and gender-matched
      controls. RESULTS: Ever smoking and ever use of any alcohol were not associated
      with risk of UGI cancer; only modest associations were observed between ESCC risk
      and highest cumulative smoking exposure, as well as GNCA risk and beer drinking.
      While several associations were noted for socioeconomic and some dietary
      variables with one or two UGI cancers, the strongest and most consistent
      relations for all three individual UGI cancers were observed for consumption of
      scalding hot foods (risk increased 150-219% for daily vs. never users) and fresh
      vegetables and fruits (risk decreased 48-70% for vegetables and 46-68% for
      fruits, respectively, for high vs. low quartiles). CONCLUSION: This study
      confirms the minor role of tobacco and alcohol in UGI cancers in this region, and
      highlights thermal damage as a leading etiologic factor.

PMID- 21846599
TI  - Multiscale-patient-specific artery and atherogenesis models.
AB  - In this work, we present a platform for the development of multiscale patient
      specific artery and atherogenesis models. The platform, called ARTool, integrates
      technologies of 3-D image reconstruction from various image modalities, blood
      flow and biological models of mass transfer, plaque characterization, and plaque
      growth. Patient images are acquired for the development of the 3-D model of the
      patient specific arteries. Then, blood flow is modeled within the arterial models
      for the calculation of the wall shear stress distribution (WSS). WSS is combined
      with other patient-specific parameters for the development of the plaque
      progression models. Real-time simulation can be performed for same cases in grid
      environment. The platform is evaluated using both animal and human data.

PMID- 21846600
TI  - Multiscale modeling of insulin secretion.
AB  - Insulin secretion from pancreatic beta cells is a fundamental physiological
      process, and its impairment plays a pivotal role in the development of diabetes.
      Mathematical modeling of insulin secretion has a long history, both on the level
      of the entire body and on the cellular and subcellular scale. However, little
      direct communication between these disparate scales has been included in
      mathematical models so far. Recently, we have proposed a minimal model for the
      incretin effect by which the gut hormone glucagon-like peptide 1 (GLP-1) enhances
      insulin secretion. To understand how this model couples to cellular events, we
      use a previously published mechanistic model of insulin secretion, and show
      mathematically that induction of glucose competence in beta cells by GLP-1 can
      underlie derivative control by GLP-1.

PMID- 21846601
TI  - Predicting target displacements using ultrasound elastography and finite element
      modeling.
AB  - Soft tissue displacements during minimally invasive surgical procedures may cause
      target motion and subsequent misplacement of the surgical tool. A technique is
      presented to predict target displacements using a combination of ultrasound
      elastography and finite element (FE) modeling. A cubic gelatin/agar phantom with
      stiff targets was manufactured to obtain pre- and post-loading ultrasound radio
      frequency (RF) data from a linear array transducer. The RF data were used to
      compute displacement and strain images, from which the distribution of elasticity
      was reconstructed using an inverse FE-based approach. The FE model was
      subsequently used to predict target displacements upon application of different
      boundary and loading conditions to the phantom. The influence of geometry was
      investigated by application of the technique to a breast-shaped phantom. The
      distribution of elasticity in the phantoms as determined from the strain
      distribution agreed well with results from mechanical testing. Upon application
      of different boundary and loading conditions to the cubic phantom, the FE model
      predicted target motion were consistent with ultrasound measurements. The FE
      based approach could also accurately predict the displacement of the target upon
      compression and indentation of the breast-shaped phantom. This study provides
      experimental evidence that organ geometry and boundary conditions surrounding the
      organ are important factors influencing target motion. In future work, the
      technique presented in this paper could be used for preoperative planning of
      minimally invasive surgical interventions.

PMID- 21846602
TI  - Optimal sampling and estimation in PASL perfusion imaging.
AB  - Pulsed arterial spin labeling (PASL) techniques potentially allow the absolute,
      noninvasive quantification of brain perfusion using MRI. This can be achieved by
      fitting a kinetic model to the data acquired at a number of sampling times.
      However, the intrinsically low signal-to-noise ratio of PASL measurements usually
      requires substantial signal averaging, which may result in undesirably long
      scanning times. A judicious choice of the sampling points is, therefore, crucial
      in order to minimize scanning time, while optimizing estimation accuracy. On the
      other hand, a priori information regarding the model parameters may improve
      estimation performance. Here, we propose a Bayesian framework to determine an
      optimal sampling strategy and estimation method for the measurement of brain
      perfusion and arterial transit time (ATT). A Bayesian Fisher information
      criterion is used to determine the optimal sampling points and a MAP criterion is
      employed for the estimation of the model parameters, both taking into account the
      uncertainty in the model parameters as well as the amount of noise in the data.
      By Monte Carlo simulations, we show that using optimal compared to uniform
      sampling strategies, as well as the Bayesian estimator relative to a standard
      least squares approach, improves the accuracy of perfusion and ATT measurements.
      Moreover, we also demonstrate the applicability of the proposed approach to real
      data, with the advantage of reduced intersubject variability relative to
      conventional sampling and estimation approaches.

PMID- 21846603
TI  - GOrevenge: a novel generic reverse engineering method for the identification of
      critical molecular players, through the use of ontologies.
AB  - The ever-increasing use of ontologies in modern biological analysis and
      interpretation facilitates the understanding of the cellular procedures, their
      hierarchical organization, and their potential interactions at a system's level.
      Currently, the gene ontology serves as a paradigm, where through the annotation
      of whole genomes of certain organisms, genes subsets selected, either from high
      throughput experiments or with an established pivotal role regarding the probed
      disease, can act as a starting point for the exploration of their underlying
      functional interconnections. This may also aid the elucidation of hidden
      regulatory mechanisms among genes. Reverse engineering the functional relevance
      of genes to specific cellular pathways and vice versa, through the exploitation
      of the inner structure of the ontological vocabularies, may help impart insight
      regarding the identification and prioritization of the critical role of specific
      genes. The proposed graph-theoretical method is showcased in a pancreatic cancer
      and a T-cell acute lymphoblastic leukemia gene set, incorporating edge and Resnik
      semantic similarity metrics, and systematically evaluated regarding its
      performance.

PMID- 21846604
TI  - Zhang neural network versus gradient neural network for solving time-varying
      linear inequalities.
AB  - By following Zhang  design method, a new type of recurrent neural network [i.e.,
      Zhang neural network (ZNN)] is presented, investigated, and analyzed for online
      solution of time-varying linear inequalities. Theoretical analysis is given on
      convergence properties of the proposed ZNN model. For comparative purposes, the
      conventional gradient neural network is developed and exploited for solving
      online time-varying linear inequalities as well. Computer simulation results
      further verify and demonstrate the efficacy, novelty, and superiority of such a
      ZNN model and its method for solving time-varying linear inequalities.

PMID- 21846605
TI  - HANS: controlling ink-jet print attributes via Neugebauer primary area coverages.
AB  - Ink-jet print attributes such as color gamut, grain, and cost are consequences of
      the materials and printing technology used and of choices made during color
      management, color separation, and halftoning operation. Traditionally, color
      separation determines what amounts of the available inks to use for each
      reproducible color, and halftoning deals with the spatial distribution of inks
      that also results in the nature of their overprinting. However, using an ink
      space as a means of communication between color separation and halftoning gives
      access only to some of the printed patterns that a printing system is capable of
      and, therefore, only to a reduced range of print attributes. Here, a method,
      i.e., Halftone Area Neugebauer Separation, is proposed to gain access to all
      possible printable patterns by specifying relative area coverages of a printing
      system's Neugebauer primaries instead of only ink amounts. This results in
      delivering prints with more optimal attributes (e.g., using less ink and giving
      rise to a larger color gamut) than is possible using current methods.

PMID- 21846606
TI  - Gaussian-mixture-model-based spatial neighborhood relationships for pixel
      labeling problem.
AB  - In this paper, we present a new algorithm for pixel labeling and image
      segmentation based on the standard Gaussian mixture model (GMM). Unlike the
      standard GMM where pixels themselves are considered independent of each other and
      the spatial relationship between neighboring pixels is not taken into account,
      the proposed method incorporates this spatial relationship into the standard GMM.
      Moreover, the proposed model requires fewer parameters compared with the models
      based on Markov random fields. In order to estimate model parameters from
      observations, instead of utilizing an expectation-maximization algorithm, we
      employ gradient method to minimize a higher bound on the data negative log
      likelihood. The performance of the proposed model is compared with methods based
      on both standard GMM and Markov random fields, demonstrating the robustness,
      accuracy, and effectiveness of our method.

PMID- 21846607
TI  - Mining data from hemodynamic simulations for generating prediction and
      explanation models.
AB  - One of the most common causes of human death is stroke, which can be caused by
      carotid bifurcation stenosis. In our work, we aim at proposing a prototype of a
      medical expert system that could significantly aid medical experts to detect
      hemodynamic abnormalities (increased artery wall shear stress). Based on the
      acquired simulated data, we apply several methodologies for1) predicting
      magnitudes and locations of maximum wall shear stress in the artery, 2)
      estimating reliability of computed predictions, and 3) providing user-friendly
      explanation of the model's decision. The obtained results indicate that the
      evaluated methodologies can provide a useful tool for the given problem domain.

PMID- 21846608
TI  - Resolving the limb position effect in myoelectric pattern recognition.
AB  - Reported studies on pattern recognition of electromyograms (EMG) for the control
      of prosthetic devices traditionally focus on classification accuracy of signals
      recorded in a laboratory. The difference between the constrained nature in which
      such data are often collected and the unpredictable nature of prosthetic use is
      an example of the semantic gap between research findings and a viable clinical
      implementation. In this paper, we demonstrate that the variations in limb
      position associated with normal use can have a substantial impact on the
      robustness of EMG pattern recognition, as illustrated by an increase in average
      classification error from 3.8% to 18%. We propose to solve this problem by: 1)
      collecting EMG data and training the classifier in multiple limb positions and by
      2) measuring the limb position with accelerometers. Applying these two methods to
      data from ten normally limbed subjects, we reduce the average classification
      error from 18% to 5.7% and 5.0%, respectively. Our study shows how sensor fusion
      (using EMG and accelerometers) may be an efficient method to mitigate the effect
      of limb position and improve classification accuracy.

PMID- 21846609
TI  - Measuring increase in synchronization to identify muscle endurance limit.
AB  - Changes in surface electromyogram (sEMG) spectral content are commonly associated
      with localized muscle fatigue. However, the significance of the changes is only
      evident during pair-wise comparison and these can only be used for comparison
      between the rested and fatigued muscle and cannot be used for identifying the
      limit of muscle endurance without having the rested data for comparison. This is
      due to the large variations between sEMG at different levels of strengths of
      contraction, and between different people. This is further compounded when the
      contraction is not isometric but is cyclic because there is large variation of
      sEMG within each cycle. This research has developed a new sEMG based method for
      studying muscle fatigue and for identifying the limit of muscle endurance. It is
      based on motor unit synchronization and is called increase in synchronization
      (IIS) index. IIS index measures the level of independence between two channels of
      sEMG recorded from the muscle and is the log of the determinant of the global
      matrix ( log||G||) which is generated by performing independent component
      analysis on the two channels. The experimental results for biceps brachii
      demonstrate that when the muscle was rested, the two channels had a high degree
      of independence and the IIS index was greater than -0.7 (range -0.65 to -0.05).
      However, the channels became dependent as the muscles progressively fatigued and
      IIS index became less than -6.2 (range -7.8 to -6.3 ) at the limit of muscle
      endurance. This was irrespective of the contraction being isometric or cyclic, or
      of the level of muscle contraction.

PMID- 21846610
TI  - The effects of particulate matter sources on daily mortality: a case-crossover
      study of Barcelona, Spain.
AB  - BACKGROUND: Dozens of studies link acute exposure to particulate matter (PM) air
      pollution with premature mortality and morbidity, but questions remain about
      which species and sources in the vast PM mixture are responsible for the observed
      health effects. Although a few studies exist on the effects of species and
      sources in U.S. cities, European cities-which have a higher proportion of diesel
      engines and denser urban populations-have not been well characterized.
      Information on the effects of specific sources could aid in targeting pollution
      control and in articulating the biological mechanisms of PM. OBJECTIVES: Our
      study examined the effects of various PM sources on daily mortality for 2003
      through 2007 in Barcelona, a densely populated city in the northeast corner of
      Spain. METHODS: Source apportionment for PM <= 2.5 MUm and <= 10 um in
      aerodynamic diameter (PM2.5 and PM10) using positive matrix factorization
      identified eight different factors. Case-crossover regression analysis was used
      to estimate the effects of each factor. RESULTS: Several sources of PM2.5,
      including vehicle exhaust, fuel oil combustion, secondary nitrate/organics,
      minerals, secondary sulfate/organics, and road dust, had statistically
      significant associations (p < 0.05) with all-cause and cardiovascular mortality.
      Also, in some cases relative risks for a respective interquartile range increase
      in concentration were higher for specific sources than for total PM2.5 mass.
      CONCLUSIONS: These results along with those from our multisource models suggest
      that traffic, sulfate from shipping and long-range transport, and construction
      dust are important contributors to the adverse health effects linked to PM.

PMID- 21846612
TI  - [Induction of labor by oral administration of 50 MUg of misoprostol: a
      prospective study in Libreville (Gabon)].
AB  - OBJECTIVES: to describe and to analyze the results of our experience in inducing
      labor with the misoprostol, 50 MUg, administered orally. MATERIAL AND METHODS:
      this descriptive prospective study took place at the Josephine-Bongo Maternity
      Hospital, in Libreville, in Gabon, from 1st January 2007 to 31st December 2009.
      It included pregnancies with a gestational age greater or equal to 29  weeks of
      singletons in cephalic presentation. The induction consisted in the
      administration of one quarter of a misoprostol tablet (that is, a dose of 50 MUg)
      at 6 in the morning, fasting, and repeated every 4 h up to a maximum of five
      doses. The principal study indicators were epidemiologic characteristics, dose
      received, duration of labor, and outcome. RESULTS: the study included 91
      patients, with a mean age of 26  years. On average, women received 1.6 doses of
      50 MUg of misoprostol, for a mean dose of 78.5 MUg. A single dose of 50 MUg was
      sufficient to induce labor for 61 patients (67%), as well as for 69% of patients
      (34/49) with a parity less than or equal to 1. Delivery occurred within 24 h for
      80 patients (88%). Vaginal deliveries accounted for 86% of the births (n = 78
      patients). There were five failures (5.5%), no adverse effects, and no maternal
      complications. CONCLUSION: our series confirms the effectiveness and good
      tolerance of 50-MUg misoprostol, administered orally. This route has a period of
      rapid action, is easy to use, and requires no invasive procedures.

PMID- 21846611
TI  - Application of computational systems biology to explore environmental toxicity
      hazards.
AB  - BACKGROUND: Computer-based modeling is part of a new approach to predictive
      toxicology. OBJECTIVES: We investigated the usefulness of an integrated
      computational systems biology approach in a case study involving the isomers and
      metabolites of the pesticide dichlorodiphenyltrichloroethane (DDT) to ascertain
      their possible links to relevant adverse effects. METHODS: We extracted chemical
      protein association networks for each DDT isomer and its metabolites using
      ChemProt, a disease chemical biology database that includes both binding and gene
      expression data, and we explored protein-protein interactions using a human
      interactome network. To identify associated dysfunctions and diseases, we
      integrated protein-disease annotations into the protein complexes using the
      Online Mendelian Inheritance in Man database and the Comparative Toxicogenomics
      Database. RESULTS: We found 175 human proteins linked to p,p'-DDT, and 187 to
      o,p'-DDT.Dichlorodiphenyldichloroethylene (p,p'-DDE) was the metabolite with the
      highest number of links, with 52. We grouped proteins for each compound based on
      their disease annotations. Although the two data sources differed in linkage to
      diseases, integrated results predicted that most diseases were linked to the two
      DDT isomers. Asthma was uniquely linked with p,p'-DDT, and autism with o,p'-DDT.
      Several reproductive and neurobehavioral outcomes and cancer types were linked to
      all three compounds. CONCLUSIONS: Computer-based modeling relies on available
      information. Although differences in linkages to proteins may be due to
      incomplete data, our results appear meaningful and suggest that the parent DDT
      compounds may be responsible for more disease connections than the metabolites.
      The findings illustrate the potential use of computational approaches to
      toxicology.

PMID- 21846613
TI  - [Survey of drug dispensing errors in hospital wards].
AB  - Medication errors occur very frequently. The limited knowledge of contributing
      factors and risks prevents the development and testing of successful preventive
      strategies. OBJECTIVE: To investigate the differences between the ordered and
      dispensed drugs, and to identify the risks during medication. METHODS:
      Prospective direct observation at two inpatient hospital wards. RESULTS: The
      number of observed doses was 775 and the number of ordered doses was 806. It was
      found that from the total opportunities of 803 errors 114 errors occurred in
      dispensed drugs corresponding to an error rate of 14.1%. Among the different
      types of errors, the most important errors were: dispensing inappropriate doses
      (25.4%), unauthorized tablet halving or crushing (24.6%), omission errors (16.4%)
      and dispensing an active ingredient different from the ordered (14.2%). 87% of
      drug dispensing errors were considered as errors with minor consequences, while
      13% of errors were potentially serious. CONCLUSIONS: Direct observation of the
      drug dispensing procedure appears to be an appropriate method to observe errors
      in medication of hospital wards. The results of the study and the identified
      risks are worth to be reconsidered and prevention measures should be applied to
      everyday health care practice to improve patient safety.

PMID- 21846614
TI  - [Distribution of multiple congenital abnormalities including anotia and
      microtia].
AB  - To evaluate cases with unclassified multiple congenital abnormalities including
      microtia and anotia as component congenital abnormalities in order to reveal the
      characteristic pattern of other associated component congenital abnormalities and
      to make an attempt to establish a registry diagnosis on the pattern of associated
      congenital abnormalities and to stimulate the establishment of an international
      registry of cases with unclassified multiple congenital abnormalities comprising
      of microtia and anotia. METHODS: The large population-based dataset of the
      Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.
      RESULTS: A total of 156 cases with unclassified multiple congenital abnormalities
      including microtia and anotia were analyzed according to the number of 2-9
      component congenital abnormalities. The comparison of the distribution and
      frequency of component congenital abnormalities in these cases showed significant
      differences from the data of other unclassified multiple congenital
      abnormalities. Of the 156 cases, registry diagnosis was possible in 48 (30.8%)
      cases. CONCLUSIONS: The evaluation of available dataset of unclassified multiple
      anotia and microtia may help the delineation of new syndromes and associations
      with better prognosis and recurrence risk estimation, thus finally a better
      chance for their prevention.

PMID- 21846616
TI  - American Association of Clinical Endocrinologists medical guidelines for clinical
      practice for the diagnosis and treatment of acromegaly--2011 update.

PMID- 21846617
TI  - Long-acting subcutaneously administered insulin for glycemic control immediately
      after cardiac surgery.
AB  - OBJECTIVE: To test the hypothesis that subcutaneous administration of basal
      insulin begun immediately after cardiac surgery can decrease the need for insulin
      infusion in patients without diabetes and save nursing time. METHODS: After
      cardiac surgery, 36 adult patients without diabetes were randomly assigned to
      receive either standard treatment (control group) or insulin glargine once daily
      in addition to standard treatment (basal insulin group). Standard treatment
      included blood glucose measurements every 1 to 4 hours and intermittent insulin
      infusion to maintain blood glucose levels between 100 and 150 mg/dL. The study
      period lasted up to 72 hours. RESULTS: There were no differences in demographics
      or baseline laboratory characteristics of the 2 study groups. Mean daily blood
      glucose levels were lower in the basal insulin group in comparison with the
      control group, but the difference was not statistically significant (129.3 +/-
      9.4 mg/dL versus 132.6 +/- 7.3 mg/dL; P = .25). The mean duration of insulin
      infusion was significantly shorter in the basal insulin group than in the control
      group (16.3 +/- 10.7 hours versus 26.6 +/- 17.3 hours; P = .04). Nurses tested
      blood glucose a mean of 8.3 +/- 3.5 times per patient per day in the basal
      insulin group and 12.0 +/- 4.7 times per patient per day in the control group (P
      = .01). There was no occurrence of hypoglycemia (blood glucose level <60 mg/dL)
      in either group. CONCLUSION: Once-daily insulin glargine is safe and may decrease
      the duration of insulin infusion and reduce nursing time in patients without
      diabetes who have hyperglycemia after cardiac surgery.

PMID- 21846619
TI  - American Association of Clinical Endocrinologists Medical Guidelines for Clinical
      Practice for the Diagnosis and Treatment of Acromegaly--2011 update: executive
      summary.

PMID- 21846621
TI  - Adrenal Cushing syndrome shortly after adrenal insufficiency.

PMID- 21846622
TI  - Dr. Joseph Warren: physician founder and true Tea Partyer.

PMID- 21846623
TI  - "Growing your own"... Creating a neonatal nurse practitioner team.

PMID- 21846624
TI  - Wound care in the neonatal intensive care unit.
AB  - The skin is a vital organ with key protective functions. Infants in the NICU are
      at risk for skin injury because of developmental immaturity and intensive care
      treatments. When skin injury occurs, the neonatal nurse is challenged to provide
      wound care to optimize functional and cosmetic healing. Optimal wound care
      requires basic knowledge of the mechanisms of injury, physiology of wound
      healing, host factors affecting wound healing, and wound assessment. This
      knowledge provides the basis for determining appropriate wound treatment,
      including dressing selection. Attention to pain issues associated with wound care
      is difficult because of the infant's developmental stage, but is essential
      because of the potentially negative life-long impact of pain. The premature
      infant's propensity for skin stripping limits the selection of appropriate
      dressing, as does the paucity of research examining wound care products in this
      population.

PMID- 21846625
TI  - Chromosome 22q11.2 microdeletion syndrome.
AB  - Chromosome 22q11.2 microdeletion syndrome is the most common microdeletion
      syndrome in humans. It involves the loss of genetic material on the short arm of
      one of the chromosome 22 alleles. Until advanced testing was available, this
      syndrome was known by various names including DiGeorge syndrome and velo-cardio
      facial syndrome. This syndrome has a varied presentation with significant
      abnormalities including congenital heart disease, hypocalcemia, immunologic
      deficiencies, learning disabilities, and behavioral problems. A multidisciplinary
      approach is required to diagnose and manage the varied manifestations.

PMID- 21846626
TI  - Fetus in fetu: an unusual case study for the neonatal nurse practitioner.
AB  - Fetus in fetu is an extremely unusual occurrence where a rare congenital tumor
      containing a vertebral axis, often containing parts of other organs or limbs, is
      identified. Normally identified in the newborn period, the size and location of
      the mass may result in significant multiorgan compromise. This article presents
      the challenges encountered by the neonatal intensive care unit team in providing
      care for a late preterm female infant presenting with gross abdominal distension.
      Description of the case includes preoperative management along with management of
      severe coagulopathy and hemorrhage that arose during the intraoperative and
      postsurgical course of care. A brief overview of abdominal masses in the newborn
      is presented. The importance in determining the final diagnosis of fetus in fetu
      and its differentiation from teratoma is discussed.

PMID- 21846627
TI  - Resurgence of congenital syphilis: diagnosis and treatment.
AB  - Despite comprehensive antenatal screening recommendations and inexpensive
      treatment, congenital syphilis has long been and continues to be a public health
      concern, causing substantial morbidity and adverse outcomes. The following
      article reviews syphilis etiology and presentation, clinical disease, laboratory
      diagnosis, and treatment of congenital syphilis. A case will be presented
      describing a 31-week male infant exposed to infectious syphilis in utero. The
      neonate presented with classic signs of infection at birth. After initial
      serology testing of the infant, appropriate treatment was commenced. The infant
      received crystalline penicillin G for a period of ten days in consultation with
      pediatric infectious disease specialists. As expected, the infant's rapid plasma
      reagin (RPR) titers declined by three and six months of age. An interdisciplinary
      approach provided safe and optimal care for this infant. He was discharged,
      stable, and thriving at 38 weeks corrected age. Long-term multidisciplinary
      management and follow-up were arranged.

PMID- 21846628
TI  - Micafungin.

PMID- 21846629
TI  - Teaching and learning with concept maps.
AB  - Concept maps are teaching and learning tools that incorporate visual and written
      representations of related information. Nurse educators can employ concept
      mapping in various situations to promote a deeper level of learning and to
      improve retention of information among their students. Concept mapping has been
      suggested as a tool to assist in planning nursing care and developing critical
      thinking skills, as well as for evaluation of course learning. Evidence indicates
      that concept maps provide a more authentic assessment of participants' knowledge,
      understanding, critical thinking, and ability to link concepts than do
      traditional tests.

PMID- 21846630
TI  - Strategies for successful breastfeeding in the NICU.

PMID- 21846631
TI  - Respiratory syncytial virus and the premature infant parent.

PMID- 21846634
TI  - Thirty years of Kangaroo Care science and practice.

PMID- 21846638
TI  - Ventricular fibrillation in loop recorder memories in a patient with early
      repolarization syndrome.
AB  - We report the first documentation of spontaneous ventricular fibrillation by a
      loop recorder in a patient with an ECG pattern of early repolarization (ER) in
      the inferior leads and presenting with syncope.

PMID- 21846635
TI  - Managing the personal side of health: how patient expertise differs from the
      expertise of clinicians.
AB  - BACKGROUND: When patients need health information to manage their personal
      health, they turn to both health professionals and other patients. Yet, we know
      little about how the information exchanged among patients (ie, patient expertise)
      contrasts with the information offered by health professionals (ie, clinician
      expertise). Understanding how patients' experiential expertise contrasts with the
      medical expertise of health professionals is necessary to inform the design of
      peer-support tools that meet patients' needs, particularly with the growing
      prevalence of largely unguided advice sharing through Internet-based social
      software. OBJECTIVE: The objective of our study was to enhance our understanding
      of patient expertise and to inform the design of peer-support tools. We compared
      the characteristics of patient expertise with that of clinician expertise for
      breast cancer. METHODS: Through a comparative content analysis of topics
      discussed and recommendations offered in Internet message boards and books, we
      contrasted the topic, form, and style of expertise shared in sources of patient
      expertise with sources of clinician expertise. RESULTS: Patient expertise focused
      on strategies for coping with day-to-day personal health issues gained through
      trial and error of the lived experience; thus, it was predominately personal in
      topic. It offered a wealth of actionable advice that was frequently expressed
      through the narrative style of personal stories about managing responsibilities
      and activities associated with family, friends, work, and the home during
      illness. In contrast, clinician expertise was carried through a prescriptive
      style and focused on explicit facts and opinions that tied closely to the health
      care delivery system, biomedical research, and health professionals' work. These
      differences were significant between sources of patient expertise and sources of
      clinician expertise in topic (P < .001), form (P < .001), and style (P < .001).
      CONCLUSION: Patients offer other patients substantial expertise that differs
      significantly from the expertise offered by health professionals. Our findings
      suggest that experienced patients do not necessarily serve as "amateur doctors"
      who offer more accessible but less comprehensive or detailed medical information.
      Rather, they offer valuable personal information that clinicians cannot
      necessarily provide. The characteristics of patient expertise and the resulting
      design implications that we identified will help informaticians enhance the
      design of peer-support tools that will help meet patients' diverse information
      needs.

PMID- 21846636
TI  - Live and inactivated influenza vaccines induce similar humoral responses, but
      only live vaccines induce diverse T-cell responses in young children.
AB  - BACKGROUND: Two doses of either trivalent live attenuated or inactivated
      influenza vaccines (LAIV and TIV, respectively) are approved for young children
      (>= 24 months old for LAIV and >= 6 months old for TIV) and induce protective
      antibody responses. However, whether combinations of LAIV and TIV are safe and
      equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in
      children for unclear reasons. METHODS: Children 6-35 months old were
      administered, 1 month apart, 2 doses of either TIV or LAIV, or combinations of
      LAIV and TIV in both prime/boost sequences. Influenza-specific antibodies were
      measured by hemagglutination inhibition (HAI), and T cells were studied in flow
      cytometric and functional assays. Highly conserved M1, M2, and NP peptides
      predicted to be presented by common HLA class I and II were used to stimulate
      interferon-gamma enzyme-linked immunospot responses. RESULTS: All LAIV and/or TIV
      combinations were well tolerated and induced similar HAI responses. In contrast,
      only regimens containing LAIV induced influenza-specific CD4(+), CD8(+), and
      gammadelta T cells, including T cells specific for highly conserved influenza
      peptides. CONCLUSIONS: Prime/boost combinations of LAIV and TIV in young children
      were safe and induced similar protective antibodies. Only LAIV induced CD4(+),
      CD8(+), and gammadelta T cells relevant for broadly protective heterosubtypic
      immunity. CLINICAL TRIALS REGISTRATION: NCT00231907.

PMID- 21846639
TI  - Pacing the right ventricular outflow tract septum: time to embrace the future.
AB  - Transvenous pacing has revolutionized the management of patients with potentially
      life-threatening bradycardias and at its most basic level ensures rate support to
      maintain cardiac output. However, we have known for at least a decade that pacing
      from the right ventricle (RV) apex can induce left ventricle (LV) dysfunction,
      atrial fibrillation, heart failure, and maybe an increased mortality. Although
      pacemaker manufacturers have developed successful pacing algorithms designed to
      minimize unnecessary ventricular pacing, it cannot be avoided in a substantial
      proportion of pacemaker-dependent patients. Just as there is undoubted evidence
      that RV apical pacing is injurious, there is emerging evidence that pacing from
      the RV septum is associated with a shorter duration of activation, improved
      haemodynamics, and less LV remodelling. The move from traditional RV apical
      pacing to RV septal pacing requires a change in mindset for many practitioners.
      The anatomical landmarks and electrocardiograph features of RV septal pacing are
      well described and easily recognized. While active fixation is required to place
      the lead on the septum, shaped stylets are now available to assist the implanter.
      In addition, concerns about the stability and longevity of steroid-eluting active
      fixation leads have proven to be unfounded. We therefore encourage all implanters
      to adopt RV septal pacing to minimize the potential of harm to their patients.

PMID- 21846641
TI  - Approach to unexplained sudden death in the young: proactive during life and
      prospective at death.

PMID- 21846642
TI  - Pacing-induced cardiomyopathy in patients with right ventricular stimulation for
      >15 years.
AB  - AIMS: The prevalence of pacing-induced cardiomyopathy (PiCMP) has been reported
      to be 9% 1 year after implantation. As long-term data are sparse, the aim of our
      study was to evaluate the prevalence of PiCMP in a cohort of patients with at
      least 15 years of right ventricular (RV) pacing. METHODS AND RESULTS: Inclusion
      criteria were RV stimulation for at least 15 years due to atrioventricular block
      III degrees  and absence of structural heart disease at the time of initial
      implantation. All patients were examined by echocardiography and spiroergometry.
      Pacing-induced cardiomyopathy was pre-defined as left ventricular (LV) ejection
      fraction (LVEF) <=45%, dyskinesia during RV pacing and absence of other known
      causes of cardiomyopathy. Twenty-six patients from our outpatient department met
      the inclusion criteria. Pacing-induced cardiomyopathy was diagnosed in four
      patients (15.4%). Echocardiography showed significant LV remodelling in PiCMP
      patients [LVEF 41.0 +/- 4.5%, LV end-diastolic diameter (LVEDD) 54.0 +/- 2.7 mm]
      compared with patients with preserved LVEF (LVEF 61.2 +/- 5.8%, P = 0.002, LVEDD
      45.6 +/- 4.0 mm, P= 0.004). There were no significant differences regarding age,
      gender, duration of RV pacing, heart rate, interventricular mechanical delay, QRS
      duration or prevalence of sinus rhythm, and arterial hypertension between both
      groups. The longest intraventricular delay was significantly shorter in patients
      with preserved LVEF (65.5 +/- 43.0 ms) compared with PiCMP patients (112.5 +/-
      15.0 ms, P= 0.043). Exercise capacity and quality of life did not differ
      significantly between both groups. CONCLUSION: Considering the very long duration
      of RV stimulation in our study population (24.6 +/- 6.6 years), the prevalence of
      PiCMP was remarkably low. Pacing-induced cardiomyopathy was associated with more
      pronounced intraventricular dyssynchrony.

PMID- 21846643
TI  - Impact of prophylactic corticosteroids on systemic inflammation after extensive
      atrial ablation in pigs.
AB  - AIMS: Prophylactic corticosteroids have been reported to attenuate the increase
      in C-reactive protein (CRP) and the incidence of atrial fibrillation (AF) both
      after heart surgery and AF ablation. We tested the impact of a single
      prophylactic corticosteroid dose on ultrasensitive CRP 24 h and 14 days after
      extensive linear atrial ablation (8 mm or 3.5 irrigated tip) guided by
      electroanatomical mapping (NavX) in pigs with normal hearts. METHODS AND RESULTS:
      Pigs (n = 19; 35 kg) were divided into three groups: corticoid (n = 7), atrial
      ablation with administration of 500 mg methylprednisolone intravenous at
      anaesthetic induction; control (n = 7), atrial ablation only; and sham (n = 5),
      surgical procedure without ablation. Troponin and CRP were measured before, 24 h
      and 14 days after the procedure. After sacrifice, lesions were analysed
      macroscopically and histologically. Linear lesions were created in the right (n =
      23) and left (n = 21) atrium of 14 animals, with no difference between groups. In
      all groups there was elevation of troponin and CRP 24 h after ablation, with a
      return to baseline values after 14 days. However, CRP levels of the control,
      corticoid, and sham groups were similar at all three time points analysed
      (baseline P = 0.52, 24 h P = 0.21, 14 days P = 0.66). Histological analysis did
      not show any difference between corticoid and control groups. CONCLUSION: In this
      model, extensive biatrial RF ablation, per se, does not promote systemic
      inflammation. The use of a prophylactic single corticoid dose before ablation did
      not prevent systemic inflammation or alter the healing of the lesions.

PMID- 21846644
TI  - Prevalence and characteristics of idiopathic right ventricular outflow tract
      arrhythmias associated with J-waves.
AB  - AIM: The arrhythmogenic relationship between the presence of J-waves during sinus
      rhythm and idiopathic ventricular tachycardia (VT) or pre-mature ventricular
      contractions (PVCs) originating from the right ventricular outflow tract (RVOT)
      has not been reported. The aim of this study was to investigate the prevalence
      and characteristics of idiopathic RVOT-VT/PVCs associated with J-waves. METHODS
      AND RESULTS: The study enrolled 138 consecutive idiopathic RVOT-VT/PVC patients
      undergoing radiofrequency catheter ablation (RFCA) and 276 age- and gender
      matched control subjects. The prevalence of J-waves was assessed in each cohort,
      and the clinical and electrophysiological data were compared between the RVOT
      VT/PVC patients with J-waves (J-RVOT-VT/PVC group) and those without (non-J-RVOT
      VT/PVC group). J-waves were more common among patients with idiopathic RVOT
      VT/PVCs than among the matched control subjects (40 vs. 16% P < 0.001). The J
      RVOT-VT/PVC group had a higher incidence of sustained VT (25 vs. 5%, P < 0.01),
      shorter VT cycle length (302 +/- 57 vs. 351 +/- 58 ms, P < 0.001), and more
      episodes of syncope (25 vs. 2%, P < 0.001) than did the non-J-RVOT-VT/PVC group.
      However, no patients demonstrated any ventricular fibrillation (VF) or cardiac
      sudden death in either group. CONCLUSIONS: There was a high prevalence of J-waves
      in the idiopathic RVOT-VT/PVC patients referred for RFCA. Although patients with
      idiopathic RVOT arrhythmias associated with J-waves might have a more enhanced
      arrhythmogenicity than those without J-waves, the significance of those J-waves
      was limited in terms of the prognosis and VF.

PMID- 21846645
TI  - Percutaneous balloon venoplasty of pacemaker-associated superior vena cava
      obstruction to facilitate upgrade to a biventricular pacing system.
AB  - Superior vena cava (SVC) obstruction is an uncommon, but serious, complication of
      transvenous device implantation. We present a case of a 52-year-old lady admitted
      for upgrade to a biventricular pacemaker with significant SVC stenosis.
      Percutaneous balloon venoplasty of the SVC followed by insertion of biventricular
      pacing leads was carried out as a single procedure with no complications.

PMID- 21846646
TI  - Clinical and echocardiographic correlates of intra-atrial conduction delay.
AB  - AIMS: The total atrial conduction time (TACT) is an important
      electrophysiological parameter. We developed a new transthoracic
      echocardiographic tool (PA-TDI). The PA-TDI interval is a reflection of the TACT.
      In the present study, we evaluated the clinical and echocardiographic correlates
      of intra-atrial conduction delay. METHODS AND RESULTS: We studied 427 patients
      without class I anti-arrhythmic agents or amiodarone. All patients underwent an
      echocardiogram and the PA-TDI interval was measured. Patient characteristics were
      recorded. The mean PA-TDI was 157 +/- 22 ms. Multivariate linear regression
      analysis revealed that atrial fibrillation (AF) in history (B = 9.7; 95%CI 5.7
      13.8; P < 0.001), hypertension (B = 5.5; 95%CI 1.4-9.8; P = 0.01), clinically
      relevant valve disease (B = 5.7; 95%CI 0.5-10.8; P = 0.03), age (B = 5; 95%CI 3.3
      6.6; P < 0.001), and body mass index (BMI; B = 2.6; 95%CI 0.3-4.9; P = 0.026)
      were independently associated with the PA-TDI interval. On the echocardiogram:
      the aortic diameter (B = 0.7; 95%CI 0.2-1.2; P = 0.009), left atrial dimension (B
      = 0.9; 95%CI 0.5-1.3; P < 0.001), mitral valve E-wave deceleration time (B = 0.1;
      95%CI 0.1-0.1; P < 0.001), aortic incompetence (B = 13; 95%CI 3.3-22.6; P =
      0.008), and mitral incompetence (B = 11; 95%CI 3.6-17.5; P < 0.003) were
      independently associated with the PA-TDI interval. CONCLUSION: This study is the
      largest to investigate the relation between the atrial conduction time,
      underlying heart diseases, and echocardiographic parameters. We found that the PA
      TDI was independently prolonged in patients with a history of AF, hypertension,
      valve disease, higher age, and a higher BMI. Signs of diastolic dysfunction,
      valve incompetence, and enlarged atrium or aortic root on the echocardiogram were
      associated with a prolonged PA-TDI. This suggests that early and aggressive
      treatment of hypertension, diastolic dysfunction, and obesity could prevent intra
      atrial conduction delay.

PMID- 21846647
TI  - Induction of ventricular tachycardia during radiofrequency ablation via pulmonary
      vein ablation catheter in a patient with an implanted pacemaker.
AB  - Pulmonary vein isolation in a dual-chamber pacemaker patient using the pulmonary
      vein ablation catheter (PVAC) system resulted in perpetual induction of
      ventricular tachycardia (VT) during radio frequency energy application. Induction
      of VT was abolished by programming the PVAC-system to a pure bipolar ablation
      mode. Patients with implanted devices should be closely monitored when using the
      PVAC system in unipolar modes.

PMID- 21846648
TI  - Long-term clinical outcome of patients with persistent right ventricle
      dysfunction or pulmonary hypertension after acute pulmonary embolism.
AB  - AIMS: Persistent, echocardiography-assessed right ventricle dysfunction (RVD)
      and/or pulmonary hypertension (PHT) are relatively frequent findings after an
      acute pulmonary embolism (PE). It has been suggested that echocardiography might
      predict long-term adverse events. Our objectives were to evaluate the prognostic
      value of RVD or isolated PHT 6 months after an acute PE with regard to all-cause
      mortality or venous thromboembolism (VTE) recurrence. METHODS AND RESULTS: In a
      previous study, echocardiography was used to assess RVD or PHT on admission and 6
      months after an acute PE in 101 consecutive, haemodynamically stable pulmonary
      patients. We assessed the subsequent vital status and incidence of recurrent VTE
      in these patients. Six patients were lost for follow-up. The other 95 patients
      were categorized as those (i) with RVD or PHT 6 months after PE (17 cases, 17.8%)
      and (ii) patients with neither RVD nor PHT (78 cases, 82.1%). After a mean+/-SD
      of 2.8+/-1.06 years, there were 9 (9.4%) deaths and 12 (12.6%) VTE recurrences.
      At multivariate analysis, only age predicted all-cause mortality [hazard ratio
      (HR): 1.081, 95% confidence interval (CI): 1.003-1.166, P=0.004]. RVD or PHT
      persistence did not appear to increase the risk of mortality or recurrent VTE.
      CONCLUSION: Persistent echocardiographic signs of right ventricular pressure
      overload 6 months after an acute PE did not predict long-term adverse outcome
      events in this study.

PMID- 21846649
TI  - Hypocalcaemia-induced transient dilated cardiomyopathy in elderly: a case report.
AB  - Hypocalcaemia is a rare cause of reversible heart failure. We reported a 76-year
      old woman who had a severe systolic heart failure. She had severe hypocalcaemia
      due to hypoparathyroidism after thyroidectomy. Echocardiography showed a dilated
      left ventricle with a depressed left ventricular ejection fraction. Serum calcium
      level was low without other biological abnormalities. After calcium
      supplementation, heart failure improved rapidly. At 2 months, the calcium level
      was in a normal range and biventricular systolic and diastolic functions returned
      to normal.

PMID- 21846650
TI  - Right ventricular diverticulum.

PMID- 21846651
TI  - Prognostic value of right ventricular diastolic function indices in hypertrophic
      cardiomyopathy.
AB  - AIMS: Despite the fact that the role of left ventricular diastolic dysfunction in
      hypertrophic cardiomyopathy (HCM) patients' prognosis has been established, the
      effect of increased right ventricular (RV) diastolic filling pressures still
      remains unclear. The purpose of this study was to determine the prognostic
      significance of transthoracic echocardiographic indices of RV diastolic function
      (tricuspid inflow and tricuspid annulus tissue Doppler imaging) in HCM patients.
      METHODS AND RESULTS: We followed up 386 patients diagnosed with HCM (aged 49.3 +/
      17.2 years; 65% male) for a median period of 67 months (interquartile range 26
      189 months). Primary endpoints were considered mortality due to heart failure
      (HF) (13 patients) and total cardiovascular (TC) mortality [HF, sudden cardiac
      death and its equivalents (35 patients)]. Patients presenting with an increased
      RV E/E(r) ratio (ratio of tricuspid in flow E wave to E(r) wave obtained by
      tissue Doppler imaging at the lateral tricuspid annulus) had a 1.6 times greater
      risk for HF mortality [hazard ratio (HR): 1.6, 95% confidence interval (CI): 1.1
      2.4, P = 0.03] while patients with shortened tricuspid E wave deceleration time
      (DTE) had a 1.1 greater risk for SCD (HR: 1.1, 95% CI: 1.01-1.2, P = 0.03).
      Following ROC analysis, the optimal RV indices' cut-off values for the
      recognition of our study endpoints were assessed [E/E(r) = 6.88, sensitivity 75%,
      specificity 77.4%, area under curve (AUC) 0.847, P = 0.017 for HF mortality and
      DTE < 239 ms, sensitivity 62.5%, specificity 56.7%, AUC 0.642, P = 0.05 for TC
      mortality]. CONCLUSION: The establishment of RV restrictive physiology appears to
      have significant predictive value in HCM, regardless of the presence of other
      detrimental risk factors.

PMID- 21846652
TI  - Embolization of multiple papillary fibroelastoma of the aortic valve as cause of
      a ST-segment elevation myocardial infarction.

PMID- 21846653
TI  - Utilisation of PACS to monitor patient CT doses.
AB  - In the past 5 y, the number of computed tomography (CT) studies has doubled at
      Dubai Health Authority hospitals. This situation, along with patient's overdoses
      reported internationally, has prompted action to establish a system to manage
      patient doses incurred due to medical imaging practices. In this work, the
      authors aim to homogenise dose reporting to monitor radiation dose levels and
      facilitate the establishment of local and national dose reference levels. The two
      hospitals enrolled in this study are equipped with three CT systems (two 4 slices
      and one 64 slices). Through the Picture Archive and Communication Systems (PACS)
      tracking system, it is mandatory to fill CT patient doses in radiology
      information system (RIS). Dose length product (mGy cm) was recorded for 2502
      adult and 178 paediatric patients. All patients' dosimetry data were collected
      from the RIS by Cogonos statistical software. The PACS data were reviewed to
      exclude incomplete data. Average and range of effective doses for adult and
      paediatric patients were calculated using an appropriate weighting factor.
      Individual accumulated effective doses for adult and paediatric patients were
      calculated for 4s-scanner-1 only. Adult average effective doses for the head
      (1482 exams) were 1.23 +/- 0.58, 2.84 +/- 0.83 and 2.98 +/- 1.103 mSv, the chest
      (545 exams) were 5.39 +/- 1.63, 21.85 +/- 5.63 and 18.19 +/- 3.22 mSv and for the
      abdomen and pelvis (1183 exams) were 10.85 +/- 4.26, 25.66 +/- 8.83 and 26.46 +/-
      13.75 mSv for 4s-scanner-1, 4s-scanner-2 and 64 s, respectively. The paediatric
      average effective dose for the head (127 exams) was 1.77 +/- 0.82 mSv, for the
      chest (22 exams) was 3.3 +/- 1.29 mSv and for the abdomen and pelvis (27 exams)
      was 6.16 +/- 2.64 mSv. Results of individual accumulated effective doses for
      adult and paediatric patients were presented. PACS dose reporting facilitated
      dosimetry clinical auditing. Effective doses obtained in this work demonstrated
      that the results of one scanner were within the international dose levels while
      the other two scanners were higher. Technical actions are recommended to
      standardise the dose levels.

PMID- 21846654
TI  - A review of the scientific basis for radiation protection of the patient.
AB  - The use of ionising radiation in medicine is the single largest man-made source
      of population exposure. Individual and collective doses to patients arising from
      the medical use of ionising radiations continue to rise significantly year on
      year. This is due to the increasing use of medical imaging procedures in modern
      healthcare systems as well as the continued development of new high dose
      techniques. This paper reviews the scientific basis for the principles of
      radiation protection as defined by the International Commission on Radiological
      Protection. These principles attempt to include exposures arising from both
      medical and non-medical applications within a common framework and have evolved
      over many years and changing socio-economic considerations. In particular, the
      concepts of justification and ALARA (doses should be as low as reasonably
      achievable), which underpin the principles for medical exposures are assessed in
      terms of their applicability to the scientific process and relevance to a rapidly
      changing technologically-led healthcare system. Radiation protection is an
      integral component of patient safety in medical practices and needs to be
      evidence based and amenable to the scientific process. The limitations imposed by
      the existing philosophy of radiation protection to the development of a
      quantitative framework for adequately assessing the performance of medical
      imaging systems are highlighted. In particular, medical practitioners will
      require quantitative guidance as to the risk-benefits arising from modern X-ray
      imaging methods if they are to make rational judgements as to the applicability
      of modern high-dose techniques to particular diagnostic and therapeutic tasks. At
      present such guidance is variable due to the lack of a rational framework for
      assessing the clinical impact of medical imaging techniques. The possible
      integration of radiation protection concepts into fundamental bio-medical imaging
      research activities is discussed.

PMID- 21846655
TI  - The end of clinical freedom.

PMID- 21846656
TI  - Commentary: the need for clinical freedom.

PMID- 21846657
TI  - Commentary: the clinical freedom worth having--commentary on Hampton (1983).

PMID- 21846658
TI  - Commentary: 'The end of clinical freedom': relevance in the era of evidence-based
      medicine.

PMID- 21846659
TI  - Commentary: Clinical freedom is dead and no one need regret its passing.

PMID- 21846660
TI  - Commentary: the death of clinical freedom.

PMID- 21846661
TI  - Selegiline transdermal system (STS) as an aid for smoking cessation.
AB  - INTRODUCTION: This study examined the efficacy and safety of selegiline
      transdermal system (STS) and brief repeated behavioral intervention (BRBI) for
      smoking cessation in heavy smokers. We hypothesized that the quit rate of
      subjects who received STS and BRBI would be significantly greater than that of
      those who received placebo patch and BRBI. METHODS: This was a double-blind,
      placebo-controlled parallel-group study in which 246 men and women were
      randomized to receive either STS (n = 121) or placebo patch (n =125) for 9 weeks.
      Recruitment targeted heavy smokers, defined as individuals with self-reported use
      of >=15 cigarettes/day in the 30 days prior to enrollment, who had smoked
      cigarettes for the past 5 years, and had an expired CO level >=9 ppm during
      screening. RESULTS: Although STS was well tolerated, the overall results
      indicated that STS with BRBI was not more effective than placebo plus BRBI for
      smoking cessation (p = .58). CONCLUSIONS: The results are discussed in relation
      to interventions for heavy smokers. Although 2 trials using oral selegiline both
      showed trends toward improved abstinence, these results indicate that STS with
      BRBI was not an effective aid for smoking cessation at the end of treatment (10
      weeks), 14, or 26 weeks.

PMID- 21846662
TI  - A qualitative study of families of a child with a nut allergy.
AB  - OBJECTIVES: The aim of this study was to explore, using qualitative methods, the
      experiences of children and their parents living with nut allergy. METHODS:
      Children with a confirmed diagnosis of peanut allergy were identified from a
      database of patients maintained at an allergy clinic at a large teaching
      hospital. Interviews with 26 families were conducted involving 11 children, 25
      mothers and 12 fathers. RESULTS: The diagnosis of nut allergy signalled a
      critical transition-or biographical disruption-in the life of the family. Parents
      took on the role of 'alert assistant' and sought to create 'safe places' where
      nuts were not permitted, but often struggled when outside the home environment.
      The option of 'passing as normal', often used by people with a chronic illness to
      avoid stigma, was not available to them. Consequently, parents often reported
      being treated as faddy, demanding, and neurotic, and children suffered from
      teasing and exclusion. The social consequences of nut allergy were worsened by
      poor labelling and control of foods and products containing nuts. DISCUSSION: In
      many ways, nut allergy may be considered a form of disability, because it imposes
      social barriers on participating fully in society.

PMID- 21846663
TI  - High allele frequency of the p.Q258X mutation and identification of a novel mis
      splicing mutation in the STAR gene in Korean patients with congenital lipoid
      adrenal hyperplasia.
AB  - OBJECTIVE: Steroidogenic acute regulatory (STAR) protein plays a crucial role in
      steroidogenesis, and mutations in the STAR gene cause congenital lipoid adrenal
      hyperplasia (CLAH). This study investigated the STAR mutation spectrum and
      functionally analyzed a novel STAR mutation in Korean patients with CLAH.
      METHODS: Mutation analysis of STAR was carried out in 25 unrelated Korean CLAH
      patients. A region of STAR comprising exons 4-7 was cloned from human genomic DNA
      into an expression vector, followed by site-directed mutagenesis and transient
      expression in COS7 cells. The splicing pattern was analyzed by in vitro
      transcription, and each transcript was functionally characterized by measuring
      pregnenolone production in COS7 cells cotransfected with the cholesterol side
      chain cleavage system. RESULTS: Mutation p.Q258X was identified in 46 of 50
      alleles (92%); mutation c.653C>T was detected in two alleles (4%); and mutations
      p.R182H and c.745-6_810del were found in one allele (2%). Reverse transcriptase
      PCR products amplified from a patient heterozygous for compound c.653C>T and
      c.745-6_810del mutation revealed multiple alternatively spliced mRNAs. In vitro
      expression analysis of a minigene consisting of exons 4-7 containing the c.653C>T
      yielded two transcripts in which exon 6 or exons 5 and 6 were skipped. The
      encoded proteins exhibited defective pregnenolone-producing ability. The c.745
      6_810del mutation led to full and partial intron retention. CONCLUSIONS: p.Q258X
      is the most common STAR mutation in Korea. A previously reported c.653C>T variant
      was found to cause aberrant splicing at the mRNA level, resulting in perturbation
      of STAR function. The c.745-6_810del mutation also resulted in aberrant splicing.

PMID- 21846664
TI  - Decision-making difficulties experienced by adults with autism spectrum
      conditions.
AB  - Autobiographical and clinical accounts, as well as a limited neuropsychological
      research literature, suggest that, in some situations, men and women with autism
      spectrum conditions (ASCs) may have difficulty making decisions. Little is known,
      however, about how people with ASCs experience decision-making or how they might
      best be supported to make decisions for themselves. In this study, we compared
      the decision-making experiences of adults with and without ASCs (n=38 and n=40,
      respectively) using a novel questionnaire and the General Decision Making Style
      inventory (GDMS, Scott & Bruce, 1995). The participants with ASCs reported
      experiencing several problems in decision-making more frequently than the
      comparison group, and were more likely to report avoidance of decision-making, as
      measured using the GDMS. The findings highlight areas of potential future
      research and inform suggestions for supporting adults with ASCs during decision
      making.

PMID- 21846666
TI  - Buried by autism: older parents' perceptions of autism.
AB  - In this study, we explored older parents' perceptions of their adult sons and
      daughters with autism in order to gain insights into how parents' beliefs about
      autism may influence their coping. Narrative analysis of in-depth interviews held
      with 16 parents aged 60 years and older of adults with autism revealed that these
      parents perceived that their son's or daughter's intelligence, sense of humour
      and social personality are blocked by autism. Adherence to these beliefs appeared
      to comprise important coping strategies that supported these parents in their
      caregiving roles by assisting them to maintain positive perceptions of their son
      or daughter with autism. Yet such beliefs also held costs for the parents,
      including reinforcing the belief that they need to regulate their own behaviour
      in order to realize the true son or daughter buried by autism.

PMID- 21846665
TI  - Increasing verbal responsiveness in parents of children with autism:a pilot
      study.
AB  - Correlational studies have revealed a positive relationship between parent verbal
      responsiveness and language outcomes in children with autism. We investigated
      whether parents of young children on the autism spectrum could learn and
      implement the specific categories of verbal responsiveness that have been
      suggested to facilitate language development. Parents were taught to increase
      their verbal responsiveness in the context of a short-term language intervention
      that included group parent education sessions, as well as individual and small
      group coaching sessions of parent-child play interactions. Parents in the
      treatment group increased their use of comments that: described their child's
      focus of attention; interpreted or expanded child communication acts; and
      prompted child communication. Preliminary treatment effects were also noted in
      children's prompted and spontaneous communication. These results support the use
      of parent-mediated interventions targeting verbal responsiveness to facilitate
      language development and communication in young children with autism.

PMID- 21846667
TI  - Prevalence and correlates of autism in a state psychiatric hospital.
AB  - This study estimated the ASD prevalence in a psychiatric hospital and evaluated
      the Social Responsiveness Scale (SRS) combined with other information for
      differential diagnosis. Chart review, SRS and clinical interviews were collected
      for 141 patients at one hospital. Diagnosis was determined at case conference.
      Receiver operating characteristic (ROC) curves were used to evaluate the SRS as a
      screening instrument. Chi-squared Automatic Interaction Detector (CHAID) analysis
      estimated the role of other variables, in combination with the SRS, in separating
      cases and non-cases. Ten percent of the sample had ASD. More than other patients,
      their onset was prior to 12 years of age, they had gait problems and intellectual
      disability, and were less likely to have a history of criminal involvement or
      substance abuse. Sensitivity (0.86) and specificity (0.60) of the SRS were
      maximized at a score of 84. Adding age of onset < 12 years and cigarette use
      among those with SRS <80 increased sensitivity to 1.00 without lowering
      specificity. Adding a history substance abuse among those with SRS >80 increased
      specificity to 0.90 but dropped sensitivity to 0.79. Undiagnosed ASD may be
      common in psychiatric hospitals. The SRS, combined with other information, may
      discriminate well between ASD and other disorders.

PMID- 21846668
TI  - How do women feel about their cervical cytology samples being used for research?
AB  - BACKGROUND AND METHODOLOGY: The introduction of liquid-based cytology (LBC) for
      cervical screening in the UK has enabled research into human papillomavirus as an
      adjunct to screening and provides potential opportunities for population-based
      research into women's health. The authors explored women's views on the use of
      remnant LBC samples for sexual and reproductive health research. A pilot study
      was conducted to assess the acceptability of collecting and storing remnant LBC
      specimens for future use in sexual and reproductive health research. Women
      attending a clinic for their routine smear test were recruited to the study. Semi
      structured interviews were conducted with a subsample of the women to explore
      acceptability issues. RESULTS: Of women invited to participate (n=369), 86%
      (n=316) consented to the storage and use of their remnant sample for research. Of
      these, 96% (n=304) consented to their sample being linked to reproductive health
      records. Women interviewed (n=23) were happy with the research process although
      unclear about what future research might be conducted on their specimen and what
      health records would be accessed. DISCUSSION AND CONCLUSION: As research becomes
      technically and ethically more complex the challenge remains to find the right
      balance between providing sufficient relevant information to ensure informed
      consent and allay participant's fears, while guarding against the inclusion of
      excessive detail. The introduction of LBC for cervical screening across the UK
      brings a new opportunity to integrate research studies within a national cervical
      screening programme. Our study suggests this is acceptable to women.

PMID- 21846669
TI  - Breakthrough bacteraemia due to tigecycline-resistant Escherichia coli with New
      Delhi metallo-beta-lactamase (NDM)-1 successfully treated with colistin in a
      patient with calciphylaxis.

PMID- 21846670
TI  - The new variant of Salmonella genomic island 1 (SGI1-V) from a Proteus mirabilis
      French clinical isolate harbours blaVEB-6 and qnrA1 in the multiple antibiotic
      resistance region.
AB  - OBJECTIVES: The clinical strain of Proteus mirabilis VB1248 isolated from a blood
      culture in August 2009 was multiresistant (i.e. resistant to beta-lactams,
      fluoroquinolones, aminoglycosides and sulphonamides). We searched for the
      presence of a Salmonella genomic island 1 (SGI1). METHODS: The whole genetic
      structure surrounding the genes involved in antibiotic resistance was
      characterized by PCR or gene walking followed by DNA sequencing. RESULTS: The new
      variant SGI1-V (42.9 kb) was located downstream of the thdF chromosomal gene.
      Genes sharing homology with phage-related genes were detected on a structure of
      8.3 kb located between the right junction of the SGI1-V and the hipB/hipA genes.
      Some genetic rearrangements occurred in the SGI1-V backbone: an insertion of 2349
      bp within the open reading frame (ORF) S014, and a deletion of 3766 bp in the
      region spanning from ORFs S021 to S025 leading to the lack of ORFs S023 and S024.
      The multidrug resistance (MDR) region of 17.1 kb was located on a complex class 1
      integron extremely different from those described so far. The cassette array
      included aacA4, aadB and dhfrA1. Adjacent to this classical structure, bla(VEB-6)
      was found flanked by 135 bp elements and bracketed by two 3'-conserved segments
      (3'-CS). Downstream of the second copy of 3'-CS, the qnrA1 gene was associated
      with common region 1. CONCLUSIONS: We have identified in P. mirabilis the new
      variant SGI1-V containing the bla(VEB-6) and qnrA1 genes in the MDR region. This
      is the first report of an extended-spectrum beta-lactamase-encoding gene and a
      qnr determinant conferring resistance to quinolones on an SGI1-like structure. It
      might constitute a source of spread of resistance to other bacterial species.

PMID- 21846671
TI  - Long-term effect of efavirenz autoinduction on plasma/peripheral blood
      mononuclear cell drug exposure and CD4 count is influenced by UGT2B7 and CYP2B6
      genotypes among HIV patients.
AB  - OBJECTIVES: We investigated the long-term effect of efavirenz autoinduction on
      its plasma/peripheral blood mononuclear cell (PBMC) exposure and the CD4 count,
      and the importance of sex and pharmacogenetic variations. METHODS: Treatment
      naive HIV patients (n = 163) received efavirenz-based antiretroviral therapy.
      Plasma and intracellular (PBMC) concentrations of efavirenz and 8
      hydroxyefavirenz were determined at weeks 4 and 16 of antiretroviral therapy. CD4
      count was determined at baseline, and at weeks 12, 24 and 48. Genotyping for
      CYP2B6*6, CYP3A5*3, CYP3A5*6, CYP3A5*7, ABCB1 3435C/T and UGT2B7 (-327G->A, *2)
      was done. RESULTS: There was a significant increase in the median plasma (32%)
      and intracellular (53%) 8-hydroxyefavirenz concentrations with a decrease in the
      efavirenz metabolic ratio (MR) (calculated by dividing the concentration of
      efavirenz by that of 8-hydroxyefavirenz) (20% and 5%, respectively) by week 16
      compared with at week 4. While the CYP2B6 genotype significantly influenced
      efavirenz pharmacokinetics at weeks 4 and 16, the effect of the UGT2B7 genotype
      and sex was significant only at week 16. The Wilcoxon matched pairs test
      indicated that the change in 8-hydroxyefavirenz concentration and efavirenz MR
      over time was significant in females and in CYP2B6*1 and UGT2B7*1 carriers. The
      intracellular 8-hydroxyefavirenz level at week 16 was a negative predictor of the
      CD4 count at week 24 (P = 0.03) and at week 48 (P = 0.007). CYP2B6 (P = 0.02) and
      UGT2B7 (P = 0.05) genotypes predicted the CD4 count at week 48. Among CYP2B6*1/*1
      and UGT2B7*1/*1 carriers there was no significant change in the mean CD4 count
      after week 24, while it continuously increased until week 48 in CYP2B6*6 and
      UGT2B7*2 carriers. CONCLUSIONS: The effects of long-term efavirenz autoinduction
      on its plasma/PBMC exposure and the CD4 count over time display wide interpatient
      variability, partly due to sex and CYP2B6 and UGT2B7 genetic variation. Patients
      with the CYP2B6*1/*1 and UGT2B7*1/*1 genotypes are at risk of suboptimal immune
      recovery due to pronounced long-term autoinduction.

PMID- 21846672
TI  - Emergence of a Neisseria gonorrhoeae clone showing decreased susceptibility to
      cefixime in England and Wales.
AB  - OBJECTIVES: The third-generation cephalosporins recommended in national
      guidelines are amongst the last remaining effective agents for treatment of
      gonorrhoea. This study characterizes gonococcal isolates with decreased cefixime
      susceptibility from England and Wales. METHODS: A total of 96 isolates of
      Neisseria gonorrhoeae exhibiting cefixime MICs of >=0.125 mg/L, either collected
      as part of the Gonococcal Resistance to Antimicrobials Surveillance Programme
      (GRASP) between 2005 and 2008 (54 from a total of 4649 isolates) or referred to
      the national reference laboratory in 2008 and 2009 (42 isolates), were tested for
      susceptibility to a range of antimicrobial agents and were typed using N.
      gonorrhoeae multiantigen sequence typing (NG-MAST). RESULTS: All 96 isolates were
      also resistant to tetracycline (MIC >=2 mg/L) and ciprofloxacin (MIC >=16 mg/L)
      and 56% showed low-level chromosomal resistance to penicillin. Where data were
      available, the mean patient age was 31 years, and 88% (83/94) of patients were
      men. Isolates referred through GRASP were predominantly from men who have sex
      with men (MSM; 29/44, 66%) and from patients of white British ethnicity (25/43,
      58%). The majority of isolates belonged either to sequence type (ST) 1407 (71/96,
      74%) or to a highly related ST that shares the tpbB allele (allele 110), but with
      a different por allele (20/96, 21%). ST1407 was found in both MSM (22/29, 76%)
      and heterosexual patients (12/15, 80%) and among all eight isolates from patients
      reporting sex abroad. CONCLUSIONS: The emergence of a clonal group of gonococci
      showing decreased susceptibility to cefixime in England and Wales highlights the
      need for continued surveillance.

PMID- 21846674
TI  - Successful therapy of treatment-emergent, non-clonal daptomycin-non-susceptible
      Enterococcus faecium infections.

PMID- 21846675
TI  - Uptake of the antileishmania drug tafenoquine follows a sterol-dependent
      diffusion process in Leishmania.
AB  - OBJECTIVES: The present study was designed to elucidate the mechanism of
      tafenoquine uptake in Leishmania and its sterol dependence. METHODS: Because
      tafenoquine is a fluorescent compound, spectrofluorimetric analysis allowed us to
      monitor its uptake by Leishmania promastigotes and intracellular amastigotes, and
      to evaluate the effect of temperature, energy and H+ gradient on drug entry. The
      influence of sterols on tafenoquine uptake in Leishmania parasites was determined
      in experiments using sterol-depleting agents such as methyl-beta-cyclodextrin or
      cholesterol oxidase. RESULTS: Tafenoquine exhibited fast entry kinetics into
      Leishmania in an energy-independent, but pH- and temperature-dependent, non
      saturable process. Furthermore, sterol depletion decreased tafenoquine uptake.
      CONCLUSIONS: These findings suggest that Leishmania takes up tafenoquine by a
      diffusion process and that decreases in membrane sterol content may induce a
      decrease in drug uptake.

PMID- 21846673
TI  - Benchmarking antibiotic use in Finnish acute care hospitals using patient case
      mix adjustment.
AB  - OBJECTIVES: It is difficult to draw conclusions about the prudence of antibiotic
      use in different hospitals by directly comparing usage figures. We present a
      patient case-mix adjustment model of antibiotic use to rank hospitals while
      taking patient characteristics into account. PATIENTS AND METHODS: Data on
      antibiotic use were collected during the national healthcare-associated infection
      (HAI) prevalence survey in 2005 in Finland in all 5 tertiary care, all 15
      secondary care and 10 (25% of 40) other acute care hospitals. The use of
      antibiotics was measured using use-days/100 patient-days during a 7day period and
      the prevalence of patients receiving at least two antimicrobials during the study
      day. Case-mix-adjusted antibiotic use was calculated by using multivariate models
      and an indirect standardization method. Parameters in the model included age,
      sex, severity of underlying diseases, intensive care, haematology, preceding
      surgery, respirator, central venous and urinary catheters, community-associated
      infection, HAI and contact isolation due to methicillin-resistant Staphylococcus
      aureus. RESULTS: The ranking order changed one position in 12 (40%) hospitals and
      more than two positions in 13 (43%) hospitals when the case-mix-adjusted figures
      were compared with those observed. In 24 hospitals (80%), the antibiotic use
      density observed was lower than expected by the case-mix-adjusted use density.
      CONCLUSIONS: The patient case-mix adjustment of antibiotic use ranked the
      hospitals differently from the ranking according to observed use, and may be a
      useful tool for benchmarking hospital antibiotic use. However, the best set of
      easily and widely available parameters that would describe both patient material
      and hospital activities remains to be determined.

PMID- 21846676
TI  - Cardiac metastasis of malignant melanoma mimicking acute coronary syndrome.

PMID- 21846677
TI  - Ischaemic postconditioning revisited: lack of effects on infarct size following
      primary percutaneous coronary intervention.
AB  - AIMS: To assess the short- and long-term effects of postconditioning (p-cond) on
      infarct size, extent of myocardial salvage, and left ventricular ejection
      fraction (LVEF) in a series of patients presenting with evolving ST-elevation
      myocardial infarction (STEMI). Previous studies have shown that p-cond during
      primary percutaneous coronary intervention (PCI) confers protection against
      ischaemia-reperfusion injury and thus might reduce myocardial infarct size.
      METHODS AND RESULTS: Seventy-nine patients undergoing PCI for a first STEMI with
      TIMI grade flow 0-1 and no collaterals were randomized to p-cond (n= 39) or
      controls (n= 40). Postconditioning was performed by applying four consecutive
      cycles of 1 min balloon inflation, each followed by 1 min deflation. Infarct
      size, myocardial salvage, and LVEF were assessed by cardiac-MRI 1 week and 6
      months after MI. Postconditioning was associated with lower myocardial salvage
      (4.1 +/- 7.2 vs. 9.1 +/- 5.8% in controls; P= 0.004) and lower myocardial salvage
      index (18.9 +/- 27.4 vs. 30.9 +/- 20.5% in controls; P= 0.038). No significant
      differences in infarct size and LVEF were found between the groups at 1 week and
      6 months after MI. CONCLUSION: This randomized study suggests that p-cond during
      primary PCI does not reduce infarct size or improve myocardial function recovery
      at both short- and long-term follow-up and might have a potential harmful effect.

PMID- 21846678
TI  - Implantable cardioverter defibrillator avoids shock during electrocution.

PMID- 21846679
TI  - Efficacy and adverse effects of ketamine as an additive for paediatric caudal
      anaesthesia: a quantitative systematic review of randomized controlled trials.
AB  - BACKGROUND: The aim of this quantitative systematic review was to assess the
      efficacy and adverse effects of ketamine added to caudal local anaesthetics in
      comparison with local anaesthetics alone in children undergoing urological, lower
      abdominal, or lower limb surgery. METHODS: The systematic search, data
      extraction, critical appraisal, and pooled data analysis were performed according
      to the PRISMA statement. All randomized controlled trials (RCTs) were included in
      this meta-analysis and relative risk (RR), mean difference (MD), and the
      corresponding 95% confidence intervals (CIs) were calculated using the
      Revman((r)) statistical software for dichotomous and continuous outcomes.
      RESULTS: Thirteen RCTs (published between 1991 and 2008) including 584 patients
      met the inclusion criteria. There was a significant longer time to first
      analgesic requirements in patients receiving ketamine in addition to a local
      anaesthetic compared with a local anaesthetic alone (MD: 5.60 h; 95% CI: 5.45
      5.76; P<0.00001). There was a lower RR for the need of rescue analgesia in
      children receiving a caudal regional anaesthesia with ketamine in addition to
      local anaesthetics (RR: 0.71; 95% CI: 0.44-1.15; P=0.16). CONCLUSIONS: Caudally
      administered ketamine, in addition to a local anaesthetic, provides prolonged
      postoperative analgesia with few adverse effects compared with local anaesthetics
      alone. There is a clear benefit of caudal ketamine, but the uncertainties about
      neurotoxicity relating to the dose of ketamine, single vs repeated doses and the
      child's age, still need to be clarified for use in clinical practice.

PMID- 21846681
TI  - Relationship between -344T/C polymorphism in the aldosterone synthase gene and
      atrial fibrillation in patients with essential hypertension.
AB  - INTRODUCTION: Aldosterone plays an important role in the pathogenesis of non
      familial atrial fibrillation (AF). We tested the hypothesis that the -344T/C
      polymorphism in the aldosterone synthase gene may be associated with non-familial
      AF in Chinese patients with hypertension. MATERIALS AND METHODS: We performed a
      1:1 paired case-control study in 310 cases of hypertension with AF and same
      number matched controls. The -344T/C polymorphism was determined with polymerase
      chain reaction-restriction fragment length polymorphism. RESULTS: The
      distribution of the CYP11B2 genotypes (TT, TC and CC) was 41.9%, 50.6%, and 7.4%
      in AF patients, which was not different from controls (48.4%, 44.5%, and 7.1%,
      chi(2) = 2.675, p = 0.263). The difference between the C allele (32.3% vs. 29.4%)
      was also not significant between two groups (chi(2) = 1.661, p = 0.197). Logistic
      regression analysis showed that LAD and LVEDD (both p < 0.001), rather than the C
      allele of the CYP11B2 gene (p= 0.107) were significant predictors for AF. The LAD
      of C allele carriers is significantly larger than that of non-C allele carriers
      (p = 0.009). CONCLUSIONS: Our results indicate that the -344T/C polymorphism in
      the aldostrone synthase gene is not associated with AF but it might be associated
      with atrial remodelling in hypertensives.

PMID- 21846680
TI  - ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation
      of the anti-apoptotic protein Mcl-1.
AB  - Glioma is the most common adult primary brain tumor. Its most malignant form,
      glioblastoma multiforme (GBM), is almost invariably fatal, due in part to the
      intrinsic resistance of GBM to radiation- and chemotherapy-induced apoptosis. We
      analyzed B-cell leukemia-2 (Bcl-2) anti-apoptotic proteins in GBM and found
      myeloid cell leukemia-1 (Mcl-1) to be the highest expressed in the majority of
      malignant gliomas. Mcl-1 was functionally important, as neutralization of Mcl-1
      induced apoptosis and increased chemotherapy-induced apoptosis. To determine how
      Mcl-1 was regulated in glioma, we analyzed the promoter and identified a novel
      functional single nucleotide polymorphism in an uncharacterized E26
      transformation-specific (ETS) binding site. We identified the ETS transcription
      factor ELK4 as a critical regulator of Mcl-1 in glioma, since ELK4 downregulation
      was shown to reduce Mcl-1 and increase sensitivity to apoptosis. Importantly the
      presence of the single nucleotide polymorphism, which ablated ELK4 binding in
      gliomas, was associated with lower Mcl-1 levels and a greater dependence on Bcl
      xL. Furthermore, in vivo, ELK4 downregulation reduced tumor formation in
      glioblastoma xenograft models. The critical role of ELK4 in Mcl-1 expression and
      protection from apoptosis in glioma defines ELK4 as a novel potential therapeutic
      target for GBM.

PMID- 21846682
TI  - Association of angiotensin II type 1-receptor gene polymorphisms with the risk of
      developing hypertension in Mexican individuals.
AB  - INTRODUCTION: Hypertension is a complex disease in which a significant
      interaction between genetic and environmental factors takes place. The renin
      angiotensin system plays an important role regulating blood pressure to maintain
      homeostasis and vascular tone. In the present work, the role of angiotensin II
      type 1-receptor (AGTR1) gene polymorphisms as susceptibility markers for
      hypertension was evaluated. MATERIALS AND METHODS: Five polymorphisms in the
      AGTR1 gene were genotyped by 5' exonuclease TaqMan genotyping assays in 239
      hypertensive and 371 non-hypertensive individuals. RESULTS: A similar
      distribution of rs275651, rs275652, rs275653, and rs5183 polymorphisms was
      observed in both studied groups. Different distribution of rs5182 genotypes was
      observed between the studied groups (p = 0.016). According to the co-dominant
      model, individuals with rs5182 CC genotype have a 1.83-fold increased risk of
      developing hypertension (p = 0.009). Polymorphisms were distributed in two
      blocks: block 1 included the rs275651, rs275652, and rs275653 polymorphisms,
      whereas block 2 included the rs5183 and rs5182 polymorphisms. Individuals with
      hypertension showed increased frequency of 'CA' haplotype of block 2 when
      compared to non-hypertensive individuals (p = 0.015, odds ratio = 1.33).
      CONCLUSION: The results suggest that the rs5182 gene polymorphism could be
      involved in the risk of developing hypertension in Mexican individuals.

PMID- 21846683
TI  - Long-term health effects of harness-mounted radio transmitters in red kites
      (Milvus milvus) in England.
AB  - In 1989, the Nature Conservancy Council and the Royal Society for the Protection
      of Birds commenced reintroduction of the red kite (Milvus milvus) according to
      International Union for Conservation of Nature criteria. Following 22 years of
      intensive effort, the red kite reintroduction programme has been a success with
      an estimated 1000 pairs now breeding in England. Post-release health surveillance
      is ongoing and has been achieved through radio-tracking, monitoring breeding at
      nest sites and pathological examinations of any red kites found dead. Tail
      mounted radio transmitters were fitted from 1989 with harness-mounted radio
      transmitters being preferentially used since 2000. Since 2000, 180 individuals
      have been recovered for postmortem examination. Eighteen of these birds had
      previously had a harness-mounted radio transmitter fitted and four of these (22
      per cent) had moderate to severe lesions associated with the presence of the
      harness and radio transmitter including chronic necrogranulomatous inflammation,
      deep muscular exposure and distorted muscular conformation. Failure to breed was
      also reported in two of these individuals over the preceding year(s), although it
      is not known whether the presence of the harness contributed to this failure.
      Duration of deployment may have been a significant factor in the formation of
      these lesions as those with lesions (n=4) had a statistically significant
      (P=0.009) longer duration of deployment compared to those without lesions (n=14).
      No lesions were reported in those red kites fitted with tail-transmitters.

PMID- 21846684
TI  - Retained surgical swabs in 13 dogs.
AB  - To report the signalment, history, clinical signs, diagnostic and surgical
      findings and outcome in dogs and cats with retained swabs, medical records of
      dogs and cats that were referred to four referral centres were reviewed. Cases in
      which a retained surgical swab was identified during surgery at the referral
      hospital were selected for further study. The signalment, history, clinical
      signs, diagnostic and surgical findings and outcome in these cases were reviewed.
      Thirteen dogs with retained surgical swabs were included in the study. Bodyweight
      ranged from 9 to 45 kg. The initial surgery was a 'non-routine' abdominal
      procedure in seven dogs, ovariohysterectomy in five dogs and perineal hernia
      repair in one dog. Time from initial surgery to presentation at the referral
      centre ranged from four days to seven years. Treatment involved major surgery in
      eight of the 13 dogs. Outcome was excellent in 12 of 13 cases, one dog was
      euthanased.

PMID- 21846685
TI  - Reanalysis of the start of the UK 1967 to 1968 foot-and-mouth disease epidemic to
      calculate airborne transmission probabilities.
AB  - The aims of this study were to statistically reassess the likelihood that
      windborne spread of foot-and-mouth disease (FMD) virus (FMDV) occurred at the
      start of the UK 1967 to 1968 FMD epidemic at Oswestry, Shropshire, and to derive
      dose-response probability of infection curves for farms exposed to airborne FMDV.
      To enable this, data on all farms present in 1967 in the parishes near Oswestry
      were assembled. Cases were infected premises whose date of appearance of first
      clinical signs was within 14 days of the depopulation of the index farm. Logistic
      regression was used to evaluate the association between infection status and
      distance and direction from the index farm. The UK Met Office's NAME atmospheric
      dispersion model (ADM) was used to generate plumes for each day that FMDV was
      excreted from the index farm based on actual historical weather records from
      October 1967. Daily airborne FMDV exposure rates for all farms in the study area
      were calculated using a geographical information system. Probit analyses were
      used to calculate dose-response probability of infection curves to FMDV, using
      relative exposure rates on case and control farms. Both the logistic regression
      and probit analyses gave strong statistical support to the hypothesis that
      airborne spread occurred. There was some evidence that incubation period was
      inversely proportional to the exposure rate.

PMID- 21846686
TI  - Continuous monitoring of pop hole usage by commercially housed free-range hens
      throughout the production cycle.
AB  - Free-range laying hens are able to move between the indoor house and range
      through exits termed pop holes. The aim of this study was to examine the
      proportion of the flock that used the pop holes and to identify patterns of
      movement throughout the flock cycle. Four flocks of free-range hens each of 1500
      birds were studied. Ten per cent of each flock were tagged with RFID (radio
      frequency identification) transponders and their pop hole activity studied
      throughout the production cycle. Within two weeks of tagging at 25, 35, 45, 55
      and 65 weeks of age, approximately 80 per cent of the tagged birds were seen in
      the pop holes and 50 per cent of the tagged birds were seen on 80 per cent of the
      days available to them after tagging. Within the flock, subpopulations of birds
      could be identified: those that never ventured to the pop holes (approximately 8
      per cent), those that used the pop holes very infrequently (approximately 8 per
      cent), those that sat in the pop holes (approximately 4 per cent), and those that
      used the pop holes frequently (approximately 80 per cent). There was an effect of
      age of the birds, time of day and daily mean temperature on pop hole usage.
      Additional factors affecting activity on particular days were wind speed,
      rainfall and hours of sunshine. The findings show that a significant proportion
      of the flock accesses the pop holes on a regular basis with only a very small
      proportion preferring to stay in the house.

PMID- 21846688
TI  - Chemoreflex activity increases prostaglandin endoperoxide synthase mRNA
      expression in the late-gestation fetal sheep brain.
AB  - Fetal sheep defend blood pressure, blood volume, and blood gases using baro- and
      chemoreflexes that influence autonomic and neuroendocrine responses. The local
      generation of prostanoids within the fetal brain is also an important component
      in activating hormone responses to these stimuli, but the relationship between
      the reflexes and prostanoid biosynthesis is unclear. The present study was
      performed to test the hypothesis that the abundances of prostaglandin
      biosynthetic enzymes in the fetal brain are dependent upon the activity of the
      baro- and chemoreflex pathways. We subjected chronically catheterized fetal sheep
      in late gestation to a 10-minute period of brachiocephalic occlusion (BCO), a
      stimulus that provokes brisk cardiovascular and neuroendocrine responses. We
      compared the central nervous system abundance of prostaglandin endoperoxide
      synthases 1 and 2 (PGHS-1 and PGHS-2) after BCO to (1) fetal sheep that had been
      subjected to BCO after chronic sinoaortic denervation plus bilateral vagotomy and
      (2) fetal sheep in which the N-methyl d-aspartate (NMDA) receptor antagonist,
      ketamine, had been administered prior to BCO. Abundances of messenger RNA (mRNA)
      for PGHS-1 and of mRNA and protein for PGHS-2 in fetal hippocampus were reduced
      significantly by either prior denervation or ketamine administration.
      Prostaglandin endoperoxide synthases 1 and 2 mRNA in pituitary were decreased and
      increased, respectively, by ketamine pretreatment. The results of this study are
      consistent with the conclusion that the expression of PGHS-1 and -2 in fetal
      hippocampus and pituitary are influenced by the baro- and/or chemoreflex pathways
      within the fetal brain in late gestation.

PMID- 21846689
TI  - AMG 479, a novel IGF-1-R antibody, inhibits endometrial cancer cell proliferation
      through disruption of the PI3K/Akt and MAPK pathways.
AB  - Our goal was to evaluate the therapeutic potential of a novel antibody to the
      insulin growth factor-1 receptor (IGF-1-R; AMG 479) in endometrial cancer cells.
      The endometrial cancer cell lines, ECC-1/PRAB72 and RL-95-2, were used. Treatment
      with AMG 479 (0.02-200 nmol/L) resulted in inhibition of cell proliferation at 72
      to 120 hours. Insulin growth factor-1 (0.15-7.5 nmol/L) stimulated growth in both
      cell lines (range of 15%-42%, P = .0025-.0445), which could be blocked by
      pretreatment with AMG 479 (mean of 29% for ECC-1/PRAB72, P = .006-.007; mean of
      36% for RL-95-2, P = .0002-.0045). AMG 479 suppressed IGF-1-R kinase activity in
      a dose-dependent manner. Cells treated with AMG 479 underwent either G1 (ECC
      1/PRAB72) or G2 (RL-95-2) arrest. AMG 479 decreased human telomerase reverse
      transcriptase (hTERT) mRNA expression in both endometrial cancer cell lines.
      Treatment with AMG 479 rapidly blocked IGF-1-induced phosphorylation of IFG-1-R,
      Akt, and p44/42. Thus, manipulation of the IGF-1-R pathway may serve as a
      promising therapeutic strategy for the treatment of endometrial cancer.

PMID- 21846690
TI  - Differential granulosa cell gene expression in young women with diminished
      ovarian reserve.
AB  - OBJECTIVE: To investigate if a diagnosis of diminished ovarian reserve (DOR) is
      associated with a differential gene profile of ovarian granulosa cells (GCs) in
      infertile women undergoing in vitro fertilization (IVF). DESIGN: Prospective
      Cohort Study. SETTING: Academic IVF Program. PATIENTS: Infertile women <38 years
      were prospectively enrolled into 2 groups: normal ovarian reserve (NOR, follicle
      stimulating hormone [FSH] < 10 mIU/mL, n = 4) and DOR (FSH >= 10.0 mIU/mL, n =
      4). INTERVENTIONS: Cumulus (C) and mural (M) GCs were isolated at egg retrieval;
      messenger RNA was extracted and transcribed. MAIN OUTCOME MEASURE(S):
      Differential gene expression in cerebellar granule cells (CGCs) in the 2 groups
      was assessed by cDNA microarray. Microarray findings were validated by
      quantitative real-time polymerase chain reaction (qRTPCR) in CGCs and explored in
      multinucleated giant cells (MGCs). RESULTS: Of the 1256 differentially regulated
      genes identified in CGCs of women with DOR, the insulin-like growth factor (IGF)
      family was a biologically relevant gene family of a priori interest.
      Downregulation of IGF1 and IGF2 ligands (-3.28- and -2.54-fold, respectively),
      and their receptors, (-3.53- and -1.32-fold downregulation of IGF1R and IGF2R,
      respectively) was identified in luteinized CGCs in women with DOR compared to
      those with NOR. Downregulation of both IGF1 and IGF 2 ligands (-4.35- and 3.89
      fold, respectively) was furthermore observed in MGCs in women with DOR compared
      to those with NOR; no differences in the expression of respective receptors were
      however observed in MGCs in the 2 groups. CONCLUSIONS: Components of the IGF gene
      family are downregulated in GCs of women with DOR. These findings maybe
      contributory to the reproductive compromise observed in women with DOR, and merit
      further exploration.

PMID- 21846693
TI  - Multiple sclerosis, cognitive dysfunction and the potential benefits of exercise.

PMID- 21846692
TI  - The effects of rivastigmine on processing speed and brain activation in patients
      with multiple sclerosis and subjective cognitive fatigue.
AB  - BACKGROUND: Cognitive decline and fatigue are typical in multiple sclerosis (MS).
      However, there is no official medication for either of these symptoms. OBJECTIVE:
      The purpose of this study was to estimate the effects of a single dose of
      rivastigmine on processing speed and associated brain activity in patients with
      MS and subjective cognitive fatigue. METHODS: Fifteen patients with MS and
      subjective cognitive fatigue and 13 healthy controls (HCs) matched for age,
      gender and education performed a neuropsychological assessment and functional
      (f)MRI. A modified version of the Paced Visual Serial Addition Test (mPVSAT) was
      used as the behavioural task during fMRIs. After the first scanning session, both
      groups were randomly divided into two subgroups receiving either rivastigmine or
      placebo. A single dose of rivastigmine or placebo was administrated double
      blindly and 2.5 hours later the scanning was repeated. RESULTS: At baseline, the
      patients with MS showed slower processing speed in mPVSAT compared with the HCs.
      They also demonstrated stronger bilateral frontal activation after sustained
      cognitive effort than the HCs. Performance improvement and a further activation
      increase in the left anterior frontal cortex and additional activation in the
      right cerebellum were observed in patients who received rivastigmine but not in
      patients on placebo, or in HCs with placebo or rivastigmine. CONCLUSION: These
      preliminary findings suggest that rivastigmine may improve cognitive processing
      speed by enhancing compensatory brain activation in patients with MS.

PMID- 21846691
TI  - Receptor-binding specificity of the human parainfluenza virus type 1
      hemagglutinin-neuraminidase glycoprotein.
AB  - The hemagglutinin-neuraminidase (HN) glycoprotein is utilized by human
      parainfluenza viruses for binding to the host cell. By the use of glycan array
      assays, we demonstrate that, in addition to the first catalytic-binding site, the
      HN of human parainfluenza virus type 1 has a second site for binding covered by N
      linked glycan. Our data suggest that attachment of the first site to sialic acid
      (SA)-linked receptors triggers exposure of the second site. We found that both
      sites bind to alpha2-3-linked SAs with a preference for a sialyl-Lewis(x) motif.
      Binding to alpha2-3-linked SAs with a sulfated sialyl-Lewis motif as well as to
      alpha2-8-linked SAs was unique for the second binding site. Neither site
      recognizes alpha2-6-linked oligosaccharides.

PMID- 21846694
TI  - Is aorto-arteritis a manifestation of primary antiphospholipid antibody syndrome?
AB  - A 23 year old female presented with dyspnea on exertion and absent pulses in the
      left upper limb. She had prior history of two first trimester abortions and pre
      eclampsia with premature delivery. A Doppler examination had revealed left
      subclavian and axillary artery thrombosis for which she had been given warfarin
      six months previously. She was admitted and investigated. Patient had low
      positive aCL IgG antibody, positive antibeta2gp1 antibody, negative lupus
      anticoagulant and negative ANA. Patient had cardiomegaly and her echocardiography
      showed severe aortic regurgitation, moderate mitral regurgitation and moderate
      pulmonary artery hypertension with poor ejection fraction with normal aortic
      root. A diagnosis of primary antiphospholipid antibody syndrome with valvular
      involvement with dilated cardiomyopathy was entertained. A CT angiogram of the
      aorta revealed narrowing and irregularity of the aorta and its multiple branches
      suggestive of type III Takayasu's arteritis. Temporal relationship suggests
      development of aorto-arteritis secondary to APS but simultaneous presence of both
      these disorders in this patient cannot be ruled out.

PMID- 21846695
TI  - Inconsistency between direct and indirect comparisons of competing interventions:
      meta-epidemiological study.
AB  - OBJECTIVE: To investigate the agreement between direct and indirect comparisons
      of competing healthcare interventions. DESIGN: Meta-epidemiological study based
      on sample of meta-analyses of randomised controlled trials. Data sources Cochrane
      Database of Systematic Reviews and PubMed. Inclusion criteria Systematic reviews
      that provided sufficient data for both direct comparison and independent indirect
      comparisons of two interventions on the basis of a common comparator and in which
      the odds ratio could be used as the outcome statistic. MAIN OUTCOME MEASURE:
      Inconsistency measured by the difference in the log odds ratio between the direct
      and indirect methods. RESULTS: The study included 112 independent trial networks
      (including 1552 trials with 478,775 patients in total) that allowed both direct
      and indirect comparison of two interventions. Indirect comparison had already
      been explicitly done in only 13 of the 85 Cochrane reviews included. The
      inconsistency between the direct and indirect comparison was statistically
      significant in 16 cases (14%, 95% confidence interval 9% to 22%). The
      statistically significant inconsistency was associated with fewer trials,
      subjectively assessed outcomes, and statistically significant effects of
      treatment in either direct or indirect comparisons. Owing to considerable
      inconsistency, many (14/39) of the statistically significant effects by direct
      comparison became non-significant when the direct and indirect estimates were
      combined. CONCLUSIONS: Significant inconsistency between direct and indirect
      comparisons may be more prevalent than previously observed. Direct and indirect
      estimates should be combined in mixed treatment comparisons only after adequate
      assessment of the consistency of the evidence.

PMID- 21846696
TI  - High fluid intake prevents first time stone formation.

PMID- 21846697
TI  - Manufacturer's reply to letter on risk of hyperkalaemia with low sodium salt.

PMID- 21846698
TI  - Government seems to have listened but not heard in reorganising public health.

PMID- 21846699
TI  - Autism is not a scientifically valid or clinically useful diagnosis.

PMID- 21846700
TI  - Consider acute hepatitis C, syphilis, and HIV in MSM with hepatitis.

PMID- 21846701
TI  - Might BMJ lead crusade against reporting only relative risks?

PMID- 21846702
TI  - More numbers needed for full reporting.

PMID- 21846703
TI  - Et tu, BMJ?

PMID- 21846704
TI  - Christian Medical Fellowship's chief executive responds to Lobby Watch article.

PMID- 21846705
TI  - MedicoLegal Investigations already exists as rapid response fraud squad.

PMID- 21846706
TI  - GPs should take annual health checks for people with learning difficulties
      seriously.

PMID- 21846707
TI  - The campaign about doctors and torture in Israel two years on.

PMID- 21846708
TI  - Audience issues were not considered in editorial on WikiProject Medicine.

PMID- 21846709
TI  - Riots on the streets.

PMID- 21846710
TI  - Childhood maltreatment is linked to recurrent depression.

PMID- 21846711
TI  - Germany passes law to attract doctors to rural areas.

PMID- 21846712
TI  - Pfizer settles with victims of Nigerian drug trial.

PMID- 21846713
TI  - Development and validation of risk prediction algorithm (QThrombosis) to estimate
      future risk of venous thromboembolism: prospective cohort study.
AB  - OBJECTIVES: To derive and validate a new clinical risk prediction algorithm
      (QThrombosis, www.qthrombosis.org) to estimate individual patients' risk of
      venous thromboembolism. DESIGN: Prospective open cohort study using routinely
      collected data from general practices. Cox proportional hazards models used in
      derivation cohort to derive risk equations evaluated at 1 and 5 years. Measures
      of calibration and discrimination undertaken in validation cohort. SETTING: 564
      general practices in England and Wales contributing to the QResearch database.
      PARTICIPANTS: Patients aged 25-84 years, with no record of pregnancy in the
      preceding 12 months or any previous venous thromboembolism, and not prescribed
      oral anticoagulation at baseline: 2,314,701 in derivation cohort and 1,240,602 in
      validation cohort. Outcomes Incident cases of venous thromboembolism, either deep
      vein thrombosis or pulmonary embolism, recorded in primary care records or linked
      cause of death records. RESULTS: The derivation cohort included 14,756 incident
      cases of venous thromboembolism from 10,095,199 person years of observation (rate
      of 14.6 per 10,000 person years). The validation cohort included 6913 incident
      cases from 4,632,694 person years of observation (14.9 per 10,000 person years).
      Independent predictors included in the final model for men and women were age,
      body mass index, smoking status, varicose veins, congestive cardiac failure,
      chronic renal disease, cancer, chronic obstructive pulmonary disease,
      inflammatory bowel disease, hospital admission in past six months, and current
      prescriptions for antipsychotic drugs. We also included oral contraceptives,
      tamoxifen, and hormone replacement therapy in the final model for women. The risk
      prediction equation explained 33% of the variation in women and 34% in men in the
      validation cohort evaluated at 5 years The D statistic was 1.43 for women and
      1.45 for men. The receiver operating curve statistic was 0.75 for both sexes. The
      model was well calibrated. CONCLUSIONS: We have developed and validated a new
      risk prediction model that quantifies absolute risk of thrombosis at 1 and 5
      years. It can help identify patients at high risk of venous thromboembolism for
      prevention. The algorithm is based on simple clinical variables which the patient
      is likely to know or which are routinely recorded in general practice records.
      The algorithm could be integrated into general practice clinical computer systems
      and used to risk assess patients before hospital admission or starting medication
      which might increase the risk of venous thromboembolism.

PMID- 21846715
TI  - Measuring quality in colorectal surgery.

PMID- 21846714
TI  - Variation in reoperation after colorectal surgery in England as an indicator of
      surgical performance: retrospective analysis of Hospital Episode Statistics.
AB  - OBJECTIVE: To describe national reoperation rates after elective and emergency
      colorectal resection and to assess the feasibility of using reoperation as a
      quality indicator derived from routinely collected data in England. DESIGN:
      Retrospective observational study of Hospital Episode Statistics (HES) data.
      SETTING: HES dataset, an administrative dataset covering the entire English
      National Health Service. PARTICIPANTS: All patients undergoing a primary
      colorectal resection in England between 2000 and 2008. MAIN OUTCOME MEASURES:
      Reoperation after colorectal resection, defined as any reoperation for an intra
      abdominal procedure or wound complication within 28 days of surgery on the index
      or subsequent admission to hospital. RESULTS: The national reoperation rate was
      6.5% (15,986/246,469). A large degree of variation was identified among
      institutions and surgeons. Even among institutions and surgical teams with high
      caseloads, threefold and fivefold differences in reoperation rates were observed
      between the highest and lowest performing trusts and surgeons. Of the NHS trusts
      studied, 14.1% (22/156) had adjusted reoperation rates above the upper 99.8%
      control limit. Factors independently associated with higher risk of reoperation
      were diagnosis of inflammatory bowel disease (odds ratio 1.33 (95% CI 1.24 to
      1.42), P<0.001), presence of multiple comorbidity (odds ratio 1.34 (1.29 to
      1.39), P<0.001), social deprivation (1.14 (1.08 to 1.20) for most deprived,
      P<0.001), male sex (1.33 (1.29 to 1.38), P<0.001), rectal resection (1.63 (1.56
      to 1.71), P<0.001), laparoscopic surgery (1.11 (1.03 to 1.20), P = 0.006), and
      emergency admission (1.21 (1.17 to 1.26), P<0.001). CONCLUSIONS: There is large
      variation in reoperation after colorectal surgery between hospitals and surgeons
      in England. If data accuracy can be assured, reoperation may allow performance to
      be checked against national standards from current routinely collected data,
      alongside other indicators such as mortality.

PMID- 21846716
TI  - Membrane microdomains modulate oligomeric ABCA1 function: impact on apoAI
      mediated lipid removal and phosphatidylcholine biosynthesis.
AB  - Recent studies have identified an ABCA1-dependent, phosphatidylcholine-rich
      microdomain, called the "high-capacity binding site" (HCBS), that binds apoA-I
      and plays a pivotal role in apoA-I lipidation. Here, using sucrose gradient
      fractionation, we obtained evidence that both ABCA1 and [125I]apoA-I associated
      with the HCBS were found localized to nonraft microdomains. Interestingly,
      phosphatidylcholine (PtdCho) was selectively removed from nonraft domains by apoA
      I, whereas sphingomyelin and cholesterol were desorbed from both detergent
      resistant membranes and nonraft domains. The modulatory role of cholesterol on
      apoA-I binding to ABCA1/HCBS was also examined. Loading cells with cholesterol
      resulted in a drastic reduction in apoA-I binding. Conversely, depletion of
      membrane cholesterol by methyl-beta-cyclodextrin treatment resulted in a
      significant increase in apoA-I binding. Finally, we obtained evidence that apoA-I
      interaction with ABCA1 promoted the activation and gene expression of key enzymes
      in the PtdCho biosynthesis pathway. Taken together, these results provide strong
      evidence that the partitioning of ABCA1/HCBS to nonraft domains plays a pivotal
      role in the selective desorption of PtdCho molecules by apoA-I, allowing an
      optimal environment for cholesterol release and regeneration of the PtdCho
      containing HCBS. This process may have important implications in preventing and
      treating atherosclerotic cardiovascular disease.

PMID- 21846717
TI  - Fibroblast growth factor 21 induces glucose transporter-1 expression through
      activation of the serum response factor/Ets-like protein-1 in adipocytes.
AB  - Fibroblast growth factor 21 (FGF21) is a liver-secreted endocrine factor with
      multiple beneficial effects on obesity-related disorders. It enhances glucose
      uptake by inducing the expression of glucose transporter-1 (GLUT1) in adipocytes.
      Here we investigated the signaling pathways that mediate FGF21-induced GLUT1
      expression and glucose uptake in vitro and in animals. Quantitative real-time PCR
      and a luciferase reporter assay showed that FGF21 induced GLUT1 expression
      through transcriptional activation. The truncation of the GLUT1 promoter from 
      3145 to -3105 bp, which contains two highly conserved serum response element
      (SRE) and E-Twenty Six (ETS) binding motif, dramatically decreased FGF21-induced
      promoter activity of the GLUT1 gene. A chromatin immunoprecipitation assay
      demonstrated that the transcription factors serum response factor (SRF) and Ets
      like protein-1 (Elk-1) were recruited to the GLUT1 promoter upon FGF21
      stimulation. The siRNA-mediated knockdown of either SRF or Elk-1 resulted in a
      marked attenuation in FGF21-induced GLUT1 expression and glucose uptake in
      adipocytes. In C57 lean mice, a single intravenous injection of FGF21 induced
      phosphorylation of Elk-1 at Ser(383) and SRF at Ser(103) and also led to the
      recruitment of Elk-1 and SRF to the GLUT1 promoter in epididymal fats. By
      contrast, such effects of in vivo FGF21 administration were blunted in high fat
      diet-induced obese mice. In conclusion, FGF21 induces GLUT1 expression and
      glucose uptake through sequential activation of ERK1/2 and SRF/Elk-1, which in
      turn triggers the transcriptional activation of GLUT1 in adipocytes. The
      impairment in this signaling pathway may contribute to FGF21 resistance in obese
      mice.

PMID- 21846718
TI  - Orientation and cellular distribution of membrane-bound catechol-O
      methyltransferase in cortical neurons: implications for drug development.
AB  - Catechol-O-methyltransferase (COMT) is a key enzyme for inactivation and
      metabolism of catechols, including dopamine, norepinephrine, caffeine, and
      estrogens. It plays an important role in cognition, arousal, pain sensitivity,
      and stress reactivity in humans and in animal models. The human COMT gene is
      associated with a diverse spectrum of human behaviors and diseases from cognition
      and psychiatric disorders to chronic pain and cancer. There are two major forms
      of COMT proteins, membrane-bound (MB) COMT and soluble (S) COMT. MB-COMT is the
      main form in the brain. The cellular distribution of MB-COMT in cortical neurons
      remains unclear and the orientation of MB-COMT on the cellular membrane is
      controversial. In this study, we demonstrate that MB-COMT is located in the cell
      body and in axons and dendrites of rat cortical neurons. Analyses of MB-COMT
      orientation with computer simulation, flow cytometry and a cell surface enzyme
      assay reveal that the C-terminal catalytic domain of MB-COMT is in the
      extracellular space, which suggests that MB-COMT can inactivate synaptic and
      extrasynaptic dopamine on the surface of presynaptic and postsynaptic neurons.
      Finally, we show that the COMT inhibitor tolcapone induces cell death via the
      mechanism of apoptosis, and its cytotoxicity is dependent on dosage and
      correlated with COMT Val/Met genotypes in human lymphoblastoid cells. These
      results suggest that MB-COMT specific inhibitors can be developed and that
      tolcapone may be less hazardous at low doses and in specific genetic backgrounds.

PMID- 21846719
TI  - Liver-specific inducible nitric-oxide synthase expression is sufficient to cause
      hepatic insulin resistance and mild hyperglycemia in mice.
AB  - Inducible nitric-oxide synthase (iNOS), a major mediator of inflammation, plays
      an important role in obesity-induced insulin resistance. Inhibition of iNOS by
      gene disruption or pharmacological inhibitors reverses or ameliorates obesity
      induced insulin resistance in skeletal muscle and liver in mice. It is unknown,
      however, whether increased expression of iNOS is sufficient to cause insulin
      resistance in vivo. To address this issue, we generated liver-specific iNOS
      transgenic (L-iNOS-Tg) mice, where expression of the transgene, iNOS, is
      regulated under mouse albumin promoter. L-iNOS-Tg mice exhibited mild
      hyperglycemia, hyperinsulinemia, insulin resistance, and impaired insulin-induced
      suppression of hepatic glucose output, as compared with wild type (WT)
      littermates. Insulin-stimulated phosphorylation of insulin receptor substrate-1
      (IRS-1) and -2, and Akt was significantly attenuated in liver, but not in
      skeletal muscle, of L-iNOS-Tg mice relative to WT mice without changes in insulin
      receptor phosphorylation. Moreover, liver-specific iNOS expression abrogated
      insulin-stimulated phosphorylation of glycogen synthase kinase-3beta, forkhead
      box O1, and mTOR (mammalian target of rapamycin), endogenous substrates of Akt,
      along with increased S-nitrosylation of Akt relative to WT mice. However, the
      expression of insulin receptor, IRS-1, IRS-2, Akt, glycogen synthase kinase
      3beta, forkhead box O1, protein-tyrosine phosphatase-1B, PTEN (phosphatase and
      tensin homolog), and p85 phosphatidylinositol 3-kinase was not altered by iNOS
      transgene. Hyperglycemia was associated with elevated glycogen phosphorylase
      activity and decreased glycogen synthase activity in the liver of L-iNOS-Tg mice,
      whereas phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and
      proliferator-activated receptor gamma coactivator-1alpha expression were not
      altered. These results clearly indicate that selective expression of iNOS in
      liver causes hepatic insulin resistance along with deranged insulin signaling,
      leading to hyperglycemia and hyperinsulinemia. Our data highlight a critical role
      for iNOS in the development of hepatic insulin resistance and hyperglycemia.

PMID- 21846720
TI  - Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain
      extender units for mitochondrial fatty acid synthesis.
AB  - The objective of this study was to identify a source of intramitochondrial
      malonyl-CoA that could be used for de novo fatty acid synthesis in mammalian
      mitochondria. Because mammalian mitochondria lack an acetyl-CoA carboxylase
      capable of generating malonyl-CoA inside mitochondria, the possibility that
      malonate could act as a precursor was investigated. Although malonyl-CoA
      synthetases have not been identified previously in animals, interrogation of
      animal protein sequence databases identified candidates that exhibited sequence
      similarity to known prokaryotic forms. The human candidate protein ACSF3, which
      has a predicted N-terminal mitochondrial targeting sequence, was cloned,
      expressed, and characterized as a 65-kDa acyl-CoA synthetase with extremely high
      specificity for malonate and methylmalonate. An arginine residue implicated in
      malonate binding by prokaryotic malonyl-CoA synthetases was found to be
      positionally conserved in animal ACSF3 enzymes and essential for activity.
      Subcellular fractionation experiments with HEK293T cells confirmed that human
      ACSF3 is located exclusively in mitochondria, and RNA interference experiments
      verified that this enzyme is responsible for most, if not all, of the malonyl-CoA
      synthetase activity in the mitochondria of these cells. In conclusion, unlike
      fungi, which have an intramitochondrial acetyl-CoA carboxylase, animals require
      an alternative source of mitochondrial malonyl-CoA; the mitochondrial ACSF3
      enzyme is capable of filling this role by utilizing free malonic acid as
      substrate.

PMID- 21846721
TI  - Pigment epithelium-derived factor (PEDF) promotes tumor cell death by inducing
      macrophage membrane tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL).
AB  - Pigment epithelium-derived factor (PEDF) is an intrinsic anti-angiogenic factor
      and a potential anti-tumor agent. The tumoricidal mechanism of PEDF, however, has
      not been fully elucidated. Here we report that PEDF induces the apoptosis of TC-1
      and SK-Hep-1 tumor cells when they are cocultured with bone marrow-derived
      macrophages (BMDMs). This macrophage-mediated tumor killing is prevented by
      blockage of TNF-related apoptosis-inducing ligand (TRAIL) following treatment
      with the soluble TRAIL receptor. PEDF also increases the amount of membrane-bound
      TRAIL on cultured mouse BMDMs and on macrophages surrounding subcutaneous tumors.
      PEDF-induced tumor killing and TRAIL induction are abrogated by peroxisome
      proliferator-activated receptor gamma (PPARgamma) antagonists or small
      interfering RNAs targeting PPARgamma. PEDF also induces PPARgamma in BMDMs.
      Furthermore, the activity of the TRAIL promoter in human macrophages is increased
      by PEDF stimulation. Chromatin immunoprecipitation and DNA pull-down assays
      confirmed that endogenous PPARgamma binds to a functional PPAR-response element
      (PPRE) in the TRAIL promoter, and mutation of this PPRE abolishes the binding of
      the PPARgamma-RXRalpha heterodimer. Also, PPARgamma-dependent transactivation and
      PPARgamma-RXRalpha binding to this PPRE are prevented by PPARgamma antagonists.
      Our results provide a novel mechanism for the tumoricidal activity of PEDF, which
      involves tumor cell killing via PPARgamma-mediated TRAIL induction in
      macrophages.

PMID- 21846722
TI  - Insights into folate/FAD-dependent tRNA methyltransferase mechanism: role of two
      highly conserved cysteines in catalysis.
AB  - The flavoprotein TrmFO methylates specifically the C5 carbon of the highly
      conserved uridine 54 in tRNAs. Contrary to most methyltransferases, the 1-carbon
      unit transferred by TrmFO derives from 5,10-methylenetetrahydrofolate and not
      from S-adenosyl-L-methionine. The enzyme also employs the FAD hydroquinone as a
      reducing agent of the C5 methylene U54-tRNA intermediate in vitro. By analogy
      with the catalytic mechanism of thymidylate synthase ThyA, a conserved cysteine
      located near the FAD isoalloxazine ring was proposed to act as a nucleophile
      during catalysis. Here, we mutated this residue (Cys-53 in Bacillus subtilis
      TrmFO) to alanine and investigated its functional role. Biophysical
      characterization of this variant demonstrated the major structural role of Cys-53
      in maintaining both the integrity and plasticity of the flavin binding site.
      Unexpectedly, gel mobility shift assays showed that, like the wild-type enzyme,
      the inactive C53A variant was capable of forming a covalent complex with a 5
      fluorouridine-containing mini-RNA. This result confirms the existence of a
      covalent intermediate during catalysis but rules out a nucleophilic role for Cys
      53. To identify the actual nucleophile, two other strictly conserved cysteines
      (Cys-192 and Cys-226) that are relatively far from the active site were replaced
      with alanine, and a double mutant C53A/C226A was generated. Interestingly, only
      mutations that target Cys-226 impeded TrmFO from forming a covalent complex and
      methylating tRNA. Altogether, we propose a revised mechanism for the m(5)U54
      modification catalyzed by TrmFO, where Cys-226 attacks the C6 atom of the
      uridine, and Cys-53 plays the role of the general base abstracting the C5 proton.

PMID- 21846723
TI  - Hemolysin induces Toll-like receptor (TLR)-independent apoptosis and multiple TLR
      associated parallel activation of macrophages.
AB  - Vibrio cholerae hemolysin (HlyA) displays bipartite property while supervising
      macrophages (MPhi). The pore-forming toxin causes profound apoptosis within 3 h
      of exposure and in parallel supports activation of the defying MPhi. HlyA-induced
      apoptosis of MPhi remains steady for 24 h, is Toll-like receptor (TLR)
      independent, and is driven by caspase-9 and caspase-7, thus involving the
      mitochondrial or intrinsic pathway. Cell activation is carried forward by time
      dependent up-regulation of varying TLRs. The promiscuous TLR association of HlyA
      prompted investigation, which revealed the beta-prism lectin domain of HlyA
      simulated TLR4 up-regulation by jacalin, a plant lectin homologue besides
      expressing CD86 and type I cytokines TNF-alpha and IL-12. However, HlyA cytolytic
      protein domain up-regulated TLR2, which controlled CD40 for continuity of cell
      activation. Expression of TOLLIP before TLR2 and TLR6 abrogated TLR4, CD40, and
      CD86. We show that the transient expression of TOLLIP leading to curbing of
      activation-associated capabilities is a plausible feedback mechanism of MPhi to
      deploy TLR2 and prolong activation involving CD40 to encounter the HlyA cytolysin
      domain.

PMID- 21846724
TI  - Lysosomal storage causes cellular dysfunction in mucolipidosis II skin
      fibroblasts.
AB  - Mucolipidosis II (ML-II) is a fatal inherited metabolic disease caused by
      deficiency of GlcNAc-phosphotransferase, which plays a role in generating the
      mannose 6-phosphate recognition marker on lysosomal enzymes. In ML-II, many
      lysosomal acid hydrolases are mistargeted out of cells, and lysosomes become
      filled with undigested substrates, which explains inclusion cell disease as an
      alternative name for this disease. In this study, we revealed various cellular
      phenotypes in ML-II skin fibroblasts. We quantitated phospholipid and cholesterol
      within cells and showed ~2-fold accumulation in ML-II as compared with normal
      cells. Lysosomal pH of ML-II cells was higher than that of normal cells (5.29 +/-
      0.08 versus 4.79 +/- 0.10, p < 0.001). The proliferated lysosomes in ML-II cells
      were accumulated ~3-fold in amount as compared with normal cells. Intracellular
      logistics including endocytosis and mannose 6-phosphate receptor recycling were
      impaired in ML-II cells. To confirm whether these ML-II cellular phenotypes
      derive from deficient lysosomal acid hydrolases within lysosomes, we performed
      supplementation of lysosomal enzymes using a partially purified total enzyme
      mixture, which was derived from the conditioned culture medium of normal skin
      fibroblasts after NH(4)Cl treatment. This supplementation corrected all of the
      previously described ML-II phenotypes. In addition, the autophagic and
      mitochondrial impairment that we have previously reported improved, and inclusion
      bodies disappeared on electron micrography following total lysosomal enzyme
      supplementation. Our results indicate that various cellular phenotypes in ML-II
      are caused by the deficiency of many lysosomal enzymes and massive accumulation
      of undigested substrates.

PMID- 21846725
TI  - Association of ActA to peptidoglycan revealed by cell wall proteomics of
      intracellular Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive intracellular bacterial pathogen that
      colonizes the cytosol of eukaryotic cells. Recent transcriptomic studies have
      revealed that intracellular L. monocytogenes alter expression of genes encoding
      envelope components. However, no comparative global analysis of this cell wall
      remodeling process is yet known at the protein level. Here, we used high
      resolution mass spectrometry to define the cell wall proteome of L. monocytogenes
      growing inside epithelial cells. When compared with extracellular bacteria
      growing in a nutrient-rich medium, a major difference found in the proteome was
      the presence of the actin assembly-inducing protein ActA in peptidoglycan
      purified from intracellular bacteria. ActA was also identified in the
      peptidoglycan of extracellular bacteria growing in a chemically defined minimal
      medium. In this condition, ActA maintains its membrane anchoring domain and
      promotes efficient bacterial entry into nonphagocytic host cells. Unexpectedly,
      Internalin-A, which mediates entry of extracellular L. monocytogenes into
      eukaryotic cells, was identified at late infection times (6 h) as an abundant
      protein in the cell wall of intracellular bacteria. Other surface proteins
      covalently bound to the peptidoglycan, as Lmo0514 and Lmo2085, were detected
      exclusively in intracellular and extracellular bacteria, respectively.
      Altogether, these data provide the first insights into the changes occurring at
      the protein level in the L. monocytogenes cell wall as the pathogen transits from
      the extracellular environment to an intracytosolic lifestyle inside eukaryotic
      cells. Some of these changes include alterations in the relative amount and the
      mode of association of certain surface proteins.

PMID- 21846726
TI  - Evidence that diacylglycerol acyltransferase 1 (DGAT1) has dual membrane topology
      in the endoplasmic reticulum of HepG2 cells.
AB  - Triacylglycerol (TAG) synthesis and secretion are important functions of the
      liver that have major impacts on health, as overaccumulation of TAG within the
      liver (steatosis) or hypersecretion of TAG within very low density lipoproteins
      (VLDL) both have deleterious metabolic consequences. Two diacylglycerol
      acyltransferases (DGATs 1 and 2) can catalyze the final step in the synthesis of
      TAG from diacylglycerol, which has been suggested to play an important role in
      the transfer of the glyceride moiety across the endoplasmic reticular membrane
      for (re)synthesis of TAG on the lumenal aspect of the endoplasmic reticular (ER)
      membrane (Owen, M., Corstorphine, C. C., and Zammit, V. A. (1997) Biochem. J.
      323, 17-21). Recent topographical studies suggested that the oligomeric enzyme
      DGAT1 is exclusively lumen facing (latent) in the ER membrane. By contrast, in
      the present study, using two specific inhibitors of human DGAT1, we present
      evidence that DGAT1 has a dual topology within the ER of HepG2 cells, with
      approximately equal DGAT1 activities exposed on the cytosolic and lumenal aspects
      of the ER membrane. This was confirmed by the observation of the loss of both
      overt (partial) and latent (total) DGAT activity in microsomes prepared from
      livers of Dgat1(-/-) mice. Conformational differences between DGAT1 molecules
      having the different topologies were indicated by the markedly disparate
      sensitivities of the overt DGAT1 to one of the inhibitors. These data suggest
      that DGAT1 belongs to the family of oligomeric membrane proteins that adopt a
      dual membrane topology.

PMID- 21846729
TI  - Is the 3D-US technique the future method of choice to accompany hysteroscopic
      sterilization to reassure women of a reliable birth control method?

PMID- 21846727
TI  - E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology
      associated with age-dependent, detrimental motor impairment.
AB  - Synucleinopathies are a group of neurodegenerative disorders associated with the
      formation of aberrant amyloid inclusions composed of the normally soluble
      presynaptic protein alpha-synuclein (alpha-syn). Parkinson disease is the most
      well known of these disorders because it bears alpha-syn pathological inclusions
      known as Lewy bodies (LBs). Mutations in the gene for alpha-syn, including the
      E46K missense mutation, are sufficient to cause Parkinson disease as well as
      other synucleinopathies like dementia with LBs. Herein, we describe transgenic
      mice expressing E46K human alpha-syn in CNS neurons that develop detrimental age
      dependent motor impairments. These animals accumulate age-dependent
      intracytoplasmic neuronal alpha-syn inclusions that parallel disease and
      recapitulate the biochemical, histological, and morphological properties of LBs.
      Surprisingly, the morphology of alpha-syn inclusions in E46K human alpha-syn
      transgenic mice more closely resemble LBs than the previously described
      transgenic mice (line M83) that express neuronal A53T human alpha-syn. E46K human
      alpha-syn mice also develop abundant neuronal tau inclusions that resemble
      neurofibrillary tangles. Subsequent studies on the ability of E46K alpha-syn to
      induce tau inclusions in cellular models suggest that both direct and indirect
      mechanisms of protein aggregation are probably involved in the formation of the
      tau inclusions observed here in vivo. Re-evaluation of presymptomatic transgenic
      mice expressing A53T human alpha-syn reveals that the formation of alpha-syn
      inclusions in mice must be synchronized; however, inclusion formation is diffuse
      within affected areas of the neuroaxis such that there was no clustering of
      inclusions. Collectively, these findings provide insights in the mechanisms of
      formation of these aberrant proteinaceous inclusions and support the notion that
      alpha-syn aggregates are involved in the pathogenesis of human diseases.

PMID- 21846728
TI  - Identification of cystatin SA as a novel inhibitor of acid ceramidase.
AB  - Autoproteolytic cleavage of the inactive acid ceramidase (AC) precursor into the
      active heterodimer exposes a free cysteine residue, leading us to study whether
      AC could be regulated by one or more members of the cystatin family. Co
      expression of the full-length AC and cystatin SA (cysSA) cDNAs led to significant
      reduction of AC activity in the transfected cells. Expression of cysSA also
      inhibited endogenous AC activity in cells and increased ceramide. Conversely,
      cysSA siRNA expression led to elevated AC activity and reduction in ceramide. The
      effects of cysSA siRNA expression could be reversed by the addition of
      recombinant cysSA into the culture media. These results were consistent with
      detection of a physical interaction between AC and cysSA, assessed by co
      immunoprecipitation and nickel-nitrilotriacetic acid affinity chromatography, and
      further supported by co-localization of the endogenous proteins using confocal
      microscopy. In vitro kinetic analysis of purified, recombinant AC and cysSA
      confirmed the transfection results and suggested a non-competitive type of
      inhibition with a K(i) in the low micromolar range. Processing of the AC
      precursor into the active form was not affected by cysSA expression, suggesting
      that it likely inhibits AC by allosteric interference. Computer modeling and
      expression studies identified several potential inhibitory domains in cysSA,
      including a small "AC-like" domain (identical to the AC cleavage site, TICT).
      Small peptides, synthesized with combinations of this and a "cystatin-like"
      domain (QXVXG), exhibited significant AC inhibition as well. Such peptide-based
      AC inhibitors could potentially be used to regulate AC activity in cancer cells
      that are known to overexpress this enzyme alone and in combination with
      conventional anti-cancer drugs.

PMID- 21846730
TI  - 3D ultrasound to assess the position of tubal sterilization microinserts.
AB  - BACKGROUND: The aim of this study was to assess the diagnostic accuracy of three
      dimensional ultrasound (3D-US) for determining the position of Essure
      microinserts and the success of sterilization by the Essure method. METHODS: This
      retrospective observational study examined the case records of 311 women who
      underwent hysteroscopic sterilization from October 2002 through October 2008.
      Imaging with 3D-US or pelvic X-radiography or both was performed 3 months after
      the procedure to verify device position. Hysterosalpingography (HSG) was
      performed when a bilateral procedure was not completed because of a history of
      salpingectomy or blocked tube, when doubt persisted after 3D-US or pelvic
      radiography, or for comparative purposes in a prospective study. The positions
      seen on 3D-US were classified in four categories according to a specific scale we
      devised. RESULTS: The insertion procedure was completed in 94.2% patients. Only
      90.5% underwent imaging verification of the device 3 months afterwards. In all,
      227 3D-US, 175 pelvic radiography and 64 HSG imaging procedures were performed.
      Visualization of the device was possible in 99.6% of the 3D-US images. According
      to our classification, 3D-US was appropriate for assessing device position for
      195 (85.9%) patients. The need for HSG confirmation was significantly lower with
      3D-US than radiographic imaging (14.1 versus 26.8%, P = 0.001). 3D-US
      examinations, compared with the results of HSG as the reference test, had a
      sensitivity of 100% and a specificity of 76.6%. Neither pregnancy nor early
      expulsion occurred when 3D-US found that the devices were correctly placed.
      CONCLUSIONS: 3D-US is a simple technique for assessing the position of
      Essure((r)) microinserts, even after concomitant endometrial surgery. The 3D-US
      classification presented here appears to make it possible to use HSG for back-up
      confirmation only when the microinsert is found in a very distal position on 3D
      US and thus to protect the majority of women from the negative effects of pelvic
      radiography and HSG.

PMID- 21846732
TI  - Classifying indicators of quality: a collaboration between Dutch and English
      regulators.
AB  - INTRODUCTION: Many approaches to measuring quality in healthcare exist, generally
      employing indicators or metrics. While there are important differences, most of
      these approaches share three key areas of measurement: safety, effectiveness and
      patient experience. The European Partnership for Supervisory Organisations in
      Health Services and Social Care (EPSO) exists as a working group and discussion
      forum for European regulators. This group undertook to identify a common
      framework within which European approaches to indicators could be compared.
      APPROACH: A framework was developed to classify indicators, using four sets of
      criteria: conceptualization of quality, Donabedian definition (structure,
      process, outcome), data type (derivable, collectable from routine sources,
      special collections, samples) and data use (judgement (singular or part of
      framework) benchmarking, risk assessment). Indicators from English and Dutch
      hospital measurement programmes were put into the framework, showing areas of
      agreement and levels of comparability. In the first instance, results are only
      illustrative. CONCLUSIONS AND IMPLICATIONS: The EPSO has been a powerful driver
      for undertaking cross-European research, and this project is the first of many to
      take advantage of the access to international expertize. It has shown that
      through development of a framework that deconstructs national indicators,
      commonalities can be identified. Future work will attempt to incorporate other
      nations' indicators, and attempt cross-national comparison.

PMID- 21846731
TI  - Epstein-Barr virus in the multiple sclerosis brain: a controversial issue--report
      on a focused workshop held in the Centre for Brain Research of the Medical
      University of Vienna, Austria.
AB  - Recent epidemiological and immunological studies provide evidence for an
      association between Epstein-Barr virus infection and multiple sclerosis,
      suggesting a role of Epstein-Barr virus infection in disease induction and
      pathogenesis. A key question in this context is whether Epstein-Barr virus
      infected B lymphocytes are present within the central nervous system and the
      lesions of patients with multiple sclerosis. Previous studies on this topic
      provided highly controversial results, showing Epstein-Barr virus reactivity in B
      cells in the vast majority of multiple sclerosis cases and lesions, or only
      exceptional Epstein-Barr virus-positive B cells in rare cases. In an attempt to
      explain the reasons for these divergent results, a workshop was organized under
      the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which
      is presented here. This report summarizes the current knowledge of Epstein-Barr
      virus biology and shows that Epstein-Barr virus infection is highly complex.
      There are still major controversies, how to unequivocally identify Epstein-Barr
      virus infection in pathological tissues, particularly in situations other than
      Epstein-Barr virus-driven lymphomas or acute Epstein-Barr virus infections. It
      further highlights that unequivocal proof of Epstein-Barr virus infection in
      multiple sclerosis lesions is still lacking, due to issues related to the
      sensitivity and specificity of the detection methods.

PMID- 21846733
TI  - Methods for improving efficiency in quality measurement: the example of pain
      screening.
AB  - OBJECTIVE: Collecting unnecessary data when assessing quality of care wastes
      valuable resources. We evaluated three approaches for estimating quality-measure
      adherence and determined minimum visit data required to achieve accurate
      estimates. DESIGN: We abstracted medical records for calculating physician-level
      pain screening rates as: visit-specific, using single-visit data for each
      patient; visit-level average, using data for all patients and visits; and patient
      level average, using data from a subset of patients and visits. SETTING: VA
      Greater Los Angeles Health-care System, 2006. PARTICIPANTS: One hundred and six
      patients with Stage IV solid tumors. INTERVENTION: Pain screening at every
      medical encounter, measured by a 0-10 numeric rating scale and reported to the
      national Medicare insurance program under a 'pay-for-reporting' program. MAIN
      OUTCOME MEASURES: Amount of visit data needed to reach the smallest 95%
      confidence interval (CI) and stable pain screening estimates. RESULTS: Pain
      screening occurred at 22% (23/106; 95% CI: 14-30%) of initial visits and 50%
      (8/16; 95% CI: 25-75%) of single visits. Across all visits, screening adherence
      averaged 34% when estimated at the visit-level precision and 30% at the patient
      level. Maximum patient-level precision was reached at visit 4 (95% CI: +/- 8%)
      and visit level at visit 14 (95% CI: +/- 6%). Using patient-level and visit-level
      approaches, estimates stabilized at visits 8 and 11, respectively, and reached
      within 1 percentage point of the steady-state value at visits 4 and 9.
      CONCLUSION: To address low-pain screening among cancer patients, an oncology pain
      screening measure may be most efficiently evaluated with data from a sample of
      patients and visits. This approach may be valid for visit-level quality measures
      in other settings.

PMID- 21846735
TI  - Reconstructing the architecture of the ancestral amniote genome.
AB  - MOTIVATION: The ancestor of birds and mammals lived approximately 300 million
      years ago. Inferring its genome organization is key to understanding the
      differentiated evolution of these two lineages. However, detecting traces of its
      chromosomal organization in its extant descendants is difficult due to the
      accumulation of molecular evolution since birds and mammals lineages diverged.
      RESULTS: We address several methodological issues for the detection and assembly
      of ancestral genomic features of ancient vertebrate genomes, which encompass
      adjacencies, contiguous segments, syntenies and double syntenies in the context
      of a whole genome duplication. Using generic, but stringent, methods for all
      these problems, some of them new, we analyze 15 vertebrate genomes, including 12
      amniotes and 3 teleost fishes, and infer a high-resolution genome organization of
      the amniote ancestral genome, composed of 39 ancestral linkage groups at a
      resolution of 100 kb. We extensively discuss the validity and robustness of the
      method to variations of data and parameters. We introduce a support value for
      each of the groups, and show that 36 out of 39 have maximum support. CONCLUSIONS:
      Single methodological principle cannot currently be used to infer the
      organization of the amniote ancestral genome, and we demonstrate that it is
      possible to gather several principles into a computational paleogenomics
      pipeline. This strategy offers a solid methodological base for the reconstruction
      of ancient vertebrate genomes. AVAILABILITY: Source code, in C++ and Python, is
      available at http://www.cecm.sfu.ca/~cchauve/SUPP/AMNIOTE2010/ CONTACT:
      cedric.chauve@sfu.ca SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 21846734
TI  - A framework for analytical characterization of monoclonal antibodies based on
      reactivity profiles in different tissues.
AB  - MOTIVATION: Monoclonal antibodies (mAbs) are among the most powerful and
      important tools in biology and medicine. MAb development is of great significance
      to many research and clinical applications. Therefore, objective mAb
      classification is essential for categorizing and comparing mAb panels based on
      their reactivity patterns in different cellular species. However, typical flow
      cytometric mAb profiles present unique modeling challenges with their non
      Gaussian features and intersample variations. It makes accurate mAb
      classification difficult to do with the currently used kernel-based or
      hierarchical clustering techniques. RESULTS: To address these challenges, in the
      present study we developed a formal two-step framework called mAbprofiler for
      systematic, parametric characterization of mAb profiles. Further, we measured the
      reactivity of hundreds of new antibodies in diverse tissues using flow cytometry,
      which we successfully classified using mAbprofiler. First, mAbprofiler fits a
      mAb's flow cytometric histogram with a finite mixture model of skew t
      distributions that is robust against non-Gaussian features, and constructs a
      precise, smooth and mathematically rigorous profile. Then it performs novel curve
      clustering of the fitted mAb profiles using a skew t mixture of non-linear
      regression model that can handle intersample variation. Thus, mAbprofiler
      provides a new framework for identifying robust mAb classes, all well defined by
      distinct parametric templates, which can be used for classifying new mAb samples.
      We validated our classification results both computationally and empirically
      using mAb profiles of known classification. AVAILABILITY AND IMPLEMENTATION: A
      demonstration code in R is available at the journal website. The R code
      implementing the full framework is available from the author website -
      http://amath.nchu.edu.tw/www/teacher/tilin/software CONTACT:
      saumyadipta_pyne@dfci.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 21846736
TI  - The use of semiparametric mixed models to analyze PamChip(R) peptide array data:
      an application to an oncology experiment.
AB  - MOTIVATION: Phosphorylation by protein kinases is a central theme in biological
      systems. Aberrant protein kinase activity has been implicated in a variety of
      human diseases (e.g. cancer). Therefore, modulation of kinase activity represents
      an attractive therapeutic approach for the treatment of human illnesses. Thus,
      identification of signature peptides is crucial for protein kinase targeting and
      can be achieved by using PamChip((r)) microarray technology. We propose a
      flexible semiparametric mixed model for analyzing PamChip((r)) data. This
      approach enables the estimation of the phosphorylation rate (Velocity) as a
      function of time together with pointwise confidence intervals. RESULTS: Using a
      publicly available dataset, we show that our model is capable of adequately
      fitting the kinase activity profiles and provides velocity estimates over time.
      Moreover, it allows to test for differences in the velocity of kinase inhibition
      between responding and non-responding cell lines. This can be done at individual
      time point as well as for the entire velocity profile. CONTACT:
      pushpike@med.kuleuven.be SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21846738
TI  - Identifying associations between amino acid changes and meta information in
      alignments.
AB  - MOTIVATION: We present a method that identifies associations between amino acid
      changes in potentially significant sites in an alignment (taking into account
      several amino acid properties) with phenotypic data, through the phylogenetic
      mixed model. The latter accounts for the dependency of the observations
      (organisms). It is known from previous studies that the pathogenic aspect of many
      organisms may be associated with a single or just few changes in amino acids,
      which have a strong structural and/or functional impact on the protein.
      Discovering these sites is a big step toward understanding pathogenicity. Our
      method is able to discover such sites in proteins responsible for the pathogenic
      character of a group of bacteria. RESULTS: We use our method to predict
      potentially significant sites in the RpoS protein from a set of 209 bacteria.
      Several sites with significant differences in biological relevant regions were
      found. AVAILABILITY: Our tool is publicly available on the CRAN network at
      http://cran.r-project.org/ CONTACT: naya@pasteur.edu.uy SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 21846737
TI  - cSSMD: assessing collective activity for addressing off-target effects in genome
      scale RNA interference screens.
AB  - MOTIVATION: Off-target activity commonly exists in RNA interference (RNAi)
      screens and often generates false positives. Existing analytic methods for
      addressing the off-target effects are demonstrably inadequate in RNAi
      confirmatory screens. RESULTS: Here, we present an analytic method assessing the
      collective activity of multiple short interfering RNAs (siRNAs) targeting a gene.
      Using this method, we can not only reduce the impact of off-target activities,
      but also evaluate the specific effect of an siRNA, thus providing information
      about potential off-target effects. Using in-house RNAi screens, we demonstrate
      that our method obtains more reasonable and sensible results than current methods
      such as the redundant siRNA activity (RSA) method, the RNAi gene enrichment
      ranking (RIGER) method, the frequency approach and the t-test. CONTACT:
      xiaohua_zhang@merck.com SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21846739
TI  - Detection of synthetic glucocorticoids by liquid chromatography-tandem mass
      spectrometry in patients being investigated for Cushing's syndrome.
AB  - BACKGROUND: We report a liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the detection of four commonly prescribed steroid drugs (prednisolone,
      dexamethasone, betamethasone and beclomethasone dipropionate) while
      simultaneously measuring 24-h urine free cortisol and cortisone in patients.
      METHODS: Two hundred and fifty microlitre aliquots of urine were spiked with
      internal standard and extracted with dichloromethane. The MS instrument was
      operated with positive electrospray and multiple reaction monitoring. Two
      transitions were monitored for each analyte of interest and the ratio of the
      intensities of the product ion fragments was established. RESULTS: The LC-MS/MS
      method for the measurement of urine free cortisol and cortisone was established.
      The assay was linear up to 788 nmol/L for cortisol and 777 nmol/L for cortisone,
      with a limit of quantitation of 5.0 nmol/L for both. Analysis time per sample was
      seven minutes. Transitions for four synthetic glucocorticoids were included, and
      they were identified based on the ratio of the intensities of product ion
      fragments. Analysis of 219 samples collected from 154 patients (55 male and 99
      female) revealed the presence of prednisolone in five samples from three
      patients. Dexamethasone was detected in samples from four patients, and
      betamethasone was detected in one sample. CONCLUSION: This is the first LC-MS/MS
      method in routine use to combine quantification of urinary cortisol and cortisone
      and detection of synthetic glucocorticoids in patients being investigated for
      Cushing's syndrome. Since the most common quoted cause of Cushing's syndrome is
      steroid treatment, this is a valuable diagnostic tool.

PMID- 21846740
TI  - Symposium Issue: Fifth International Conference on Advances in Canine and Feline
      Genomics and Inherited Diseases, Baltimore, Maryland, 22-25 September 2010.
      Letter from the editor.

PMID- 21846741
TI  - A SINE insertion causes the black-and-tan and saddle tan phenotypes in domestic
      dogs.
AB  - Agouti Signaling Protein (ASIP) controls the localized expression of red and
      black pigment in the domestic dog through interaction with other genes, such as
      Melanocortin 1 Receptor and Beta-Defensin 103. Specific ASIP alleles are
      necessary for many of the coat color patterns, such as black-and-tan and saddle
      tan. Mutations in 2 ASIP alleles, a(y) and a, have previously been identified.
      Here, we characterize a mutation consisting of a short interspersed nuclear
      element (SINE) insertion in intron 1 of ASIP that allows for the differentiation
      of the a(w) wolf sable and a(t) black-and-tan alleles. The SINE insertion is
      present in dogs with the a(t) and a alleles but absent from dogs with the a(w)
      and a(y) alleles. Dogs with the saddle tan phenotype were all a(t)/a(t).
      Schnauzers were all a(w)/a(w). Genotypes of 201 dogs of 35 breeds suggest that
      there are only 4 ASIP alleles, as opposed to the 5 or 6 predicted in previous
      literature. These data demonstrate that the dominance hierarchy of ASIP is a(y) >
      a(w) > a(t) > a.

PMID- 21846742
TI  - An SNP within the angiotensin-converting enzyme distinguishes between sprint and
      distance performing Alaskan sled dogs in a candidate gene analysis.
AB  - The Alaskan sled dog offers a unique mechanism for studying the genetics of elite
      athletic performance. They are a group of mixed breed dogs, comprised of multiple
      common breeds, and a unique breed entity seen only as a part of the sled dog mix.
      Alaskan sled dogs are divided into 2 primary groups as determined by their racing
      skills. Distance dogs are capable of running over 1000 miles in 10 days, whereas
      sprint dogs run much shorter distances, approximately 30 miles, but in faster
      times, that is, 18-25 mph. Finding the genes that distinguish these 2 types of
      performers is likely to illuminate genetic contributors to human athletic
      performance. In this study, we tested for association between polymorphisms in 2
      candidate genes; angiotensin-converting enzyme (ACE) and myostatin (MSTN) and
      enhanced speed and endurance performance in 174 Alaskan sled dogs. We observed 81
      novel genetic variants within the ACE gene and 4 within the MSTN gene, including
      a polymorphism within the ACE gene that significantly (P value 2.38 * 10(-5))
      distinguished the sprint versus distance populations.

PMID- 21846744
TI  - Segregation analysis of overweight body condition in an experimental cat
      population.
AB  - The goal of this study was to analyze the mode of inheritance of an overweight
      body condition in an experimental cat population. The cat population consisted of
      95 cats of which 81 cats could be clearly classified into lean or overweight
      using the body condition scoring system according to Laflamme. The lean or
      overweight classification was then used for segregation analyses. Complex
      segregation analyses were employed to test for the significance of one
      environmental and 4 genetic models (general, mixed inheritance, major gene, and
      polygene). The general genetic model fit the data significantly better than the
      environmental model (P <= 0.0013). Among all other models employed, the major
      gene model explained the segregation of the overweight phenotype best. This is
      the first study in which a genetic component could be shown to be responsible for
      the development of overweight in cats.

PMID- 21846745
TI  - Lix1 knockout mouse does not exhibit spinal muscular atrophy phenotype.
AB  - Feline spinal muscular atrophy (SMA) is an autosomal recessive juvenile onset
      lower motor neuron disease caused by an ~ 140 kb deletion that disrupts
      expression of 2 genes, limb expression 1 (LIX1) and leucyl/cystinyl
      aminopeptidase (LNPEP). A previously generated Lnpep knockout (KO) mouse did not
      demonstrate a neuromuscular phenotype. Little is known about LIX1, except that it
      is evolutionarily conserved and highly expressed in spinal cord motor neurons. To
      determine whether loss of LIX1 alone is responsible for the feline SMA phenotype,
      a Lix1 intron 1 gene trap KO mouse line was obtained from Lexicon Genetics, Inc.
      Mating of F(1) heterozygotes produced offspring in the expected Mendelian ratios.
      KO and normal littermates were studied through 2 years of age by hanging latency,
      rotarod, inked footprint analysis, and histological methods. Disruption of Lix1
      expression did not affect survival nor result in any neuromuscular phenotype.
      Reverse transcriptase-PCR amplification of spinal cord RNA identified a Lix1
      alternative transcript beginning in intron 4 and containing exons 5 and 6. The
      alternative transcript appeared to be rodent specific, and its expression was not
      disrupted in Lix1 KO mice. Expression of the alternative transcript may have
      compensated for the loss of Lix1 in the KO mice and thus protected against motor
      neuron degeneration.

PMID- 21846746
TI  - Identification of risk loci for necrotizing meningoencephalitis in Pug dogs.
AB  - Due to their unique population structure, purebred dogs have emerged as a key
      model for the study of complex genetic disorders. To evaluate the utility of a
      newly available high-density canine whole-genome array with >170,000 single
      nucleotide polymorphisms (SNPs), genome-wide association was performed on a small
      number of case and control dogs to determine disease susceptibility loci in
      canine necrotizing meningoencephalitis (NME), a disorder with known non-Mendelian
      inheritance that shares clinical similarities with atypical variants of multiple
      sclerosis in humans. Genotyping of 30 NME-affected Pug dogs and 68 healthy
      control Pugs identified 2 loci associated with NME, including a region within dog
      leukocyte antigen class II on chromosome 12 that remained significant after
      Bonferroni correction. Our results support the utility of this high-density SNP
      array, confirm that dogs are a powerful model for mapping complex genetic
      disorders and provide important preliminary data to support in depth genetic
      analysis of NME in numerous affected breeds.

PMID- 21846743
TI  - Carnivore-specific SINEs (Can-SINEs): distribution, evolution, and genomic
      impact.
AB  - Short interspersed nuclear elements (SINEs) are a type of class 1 transposable
      element (retrotransposon) with features that allow investigators to resolve
      evolutionary relationships between populations and species while providing
      insight into genome composition and function. Characterization of a Carnivora
      specific SINE family, Can-SINEs, has, has aided comparative genomic studies by
      providing rare genomic changes, and neutral sequence variants often needed to
      resolve difficult evolutionary questions. In addition, Can-SINEs constitute a
      significant source of functional diversity with Carnivora. Publication of the
      whole-genome sequence of domestic dog, domestic cat, and giant panda serves as a
      valuable resource in comparative genomic inferences gleaned from Can-SINEs. In
      anticipation of forthcoming studies bolstered by new genomic data, this review
      describes the discovery and characterization of Can-SINE motifs as well as
      describes composition, distribution, and effect on genome function. As the
      contribution of noncoding sequences to genomic diversity becomes more apparent,
      SINEs and other transposable elements will play an increasingly large role in
      mammalian comparative genomics.

PMID- 21846748
TI  - Identification of 2 loci associated with development of myxomatous mitral valve
      disease in Cavalier King Charles Spaniels.
AB  - Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs.
      It is characterized by chronic progressive degenerative lesions of the mitral
      valve. The valve leaflets become thickened and prolapse into the left atrium
      resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium
      sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset
      of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are
      affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1
      5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no
      or mild signs of MMVD as controls, we conducted a genome-wide association study
      (GWAS) to identify loci associated with development of MMVD. We have identified a
      1.58 Mb region on CFA13 (P(genome) = 4.0 * 10(-5)) and a 1.68 Mb region on CFA14
      (P(genome) = 7.9 * 10(-4)) associated with development of MMVD. This confirms the
      power of using the dog as a model to uncover potential candidate regions involved
      in the molecular mechanisms behind complex traits.

PMID- 21846747
TI  - cAMP and IP3 signaling pathways in HEK293 cells transfected with canine olfactory
      receptor genes.
AB  - Olfactory receptors (ORs) expressed at the cell surface of olfactory sensory
      neurons lining the olfactory epithelium are the first actors of events leading to
      odor perception and recognition. As for other mammalian ORs, few dog OR have been
      deorphanized, mainly because of the absence of good methodology and the
      difficulties encountered to express ORs at the cell surface. Within this work,
      our aim was 1) to deorphanize a large subset of dog OR and 2) to compare the
      implication of the 2 main pathways, namely the cAMP and inositol 1,4,5
      triphosphate (IP3) pathways, in the transduction of the olfactory message. For
      this, we used 2 independent tests to assess the importance of each of these 2
      pathways and analyzed the responses of 47 canine family 6 ORs to a number of
      aliphatic compounds. We found these ORs globally capable of inducing
      intracellular calcium elevation through the IP3 pathway as confirmed by the use
      of specific inhibitors and/or a cAMP increase in response to aldehyde exposure.
      We showed that the implication of the cAMP or/and IP3 pathway was dependent upon
      the ligand-receptor combination rather than on one or the other partner. Finally,
      by exposing OR-expressing cells to the 21 possible pairs of C6-C12 aliphatic
      aldehydes, we confirmed that some odorant pairs may have an inhibitory or
      additive effect. Altogether, these results reinforce the notion that odorant
      receptor subfamilies may constitute functional units and call for a more
      systematic use of 2 complementary tests interrogating the cAMP and IP3 pathways
      when deorphanizing ORs.

PMID- 21846749
TI  - A rare form of persistent right aorta arch in linkage disequilibrium with the
      DiGeorge critical region on CFA26 in German Pinschers.
AB  - Persistent right aortic arch (PRAA) is a congenital vascular ring anomaly common
      in several dog breeds. In German Pinscher, the disorder is characterized by a
      left retroesophageal subclavian artery in combination with a ligamentum
      arteriosum originating at the aberrant left subclavian artery (PRAA-SA-LA). In
      this study, we genotyped 38 microsatellite markers on canine chromosome 26
      (CFA26) in German Pinschers and tested them for linkage and association. We found
      a chromosome-wide significantly linked genomic region on CFA26, which corresponds
      to the human DiGeorge syndrome critical region (DGCR). Therefore, we analyzed
      sequences from 13 genes of DGCR and the canine t-box gene TBX1. We identified a
      total of 26 polymorphisms in German Pinschers. Three of these SNPs located within
      TBX1 and one in the mitochondrial ribosomal protein L40 gene (MRPL40) were
      associated with the PRAA-SA-LA phenotype in German Pinscher. Despite linkage and
      association between PRAA-SA-LA and the canine DGCR, none of these mutations
      appeared responsible for PRAA-SA-LA. As the orthologue human region on HSA22q11.2
      is known for high susceptibility to genomic rearrangements, we suspect that in
      German Pinschers, chromosomal aberrations might cause PRAA-SA-LA.

PMID- 21846750
TI  - IgE responsiveness to Dermatophagoides farinae in West Highland white terrier
      dogs is associated with region on CFA35.
AB  - Immunoglobulin E (IgE)-mediated hypersensitivity against environmental allergens,
      commonly including Dermatophagoides farinae, is associated with atopic diseases
      in both humans and dogs. We have recently identified a family of clinically
      healthy West Highland white terriers (WHWTs) with high-serum D. farinae-IgE
      levels. In this study, we investigated the genetic mechanism controlling IgE
      responsiveness in dogs by performing a genome-wide association study (GWAS) using
      the Affymetrix V2 Dog SNP array in 31 high-IgE and 24 low-IgE responder WHWTs. A
      gene-dropping simulation method, using SIB-PAIR software, showed significant
      allelic association between serum D. farinae-specific IgE levels and a 2.3-Mb
      area on CFA35 (best empirical P = 1 * 10(-5)). A nearby candidate gene, CD83,
      encodes a protein which has important immunological functions in antigen
      presentation and regulation of humoral immune responses. We sequenced this gene
      in 2 high-IgE responders and 2 low-IgE responders and identified an intronic
      polymorphic repeat sequence with a predicted functional effect, but the
      association was insufficient to explain the GWAS association signal in this
      population (P = 1 * 10(-3)). Further studies are necessary to investigate the
      significance of these findings for IgE responsiveness and atopic disease in the
      dog.

PMID- 21846751
TI  - Genome-wide association study in Dachshund: identification of a major locus
      affecting intervertebral disc calcification.
AB  - Intervertebral disc calcification and herniation commonly affects Dachshund where
      the predisposition is caused by an early onset degenerative process resulting in
      disc calcification. A continuous spectrum of disc degeneration is seen within and
      among dog breeds, suggesting a multifactorial etiology. The number of calcified
      discs at 2 years of age determined by a radiographic evaluation is a good
      indicator of the severity of disc degeneration and thus serves as a measure for
      the risk of developing intervertebral disc herniation. The aim of the study was
      to identify genetic variants associated with intervertebral disc calcification in
      Dachshund through a genome-wide association (GWA) study. Based on thorough
      radiographic examinations, 48 cases with >= 6 disc calcifications or surgically
      treated for disc herniation and 46 controls with 0-1 disc calcifications were
      identified. GWA using the Illumina CanineHD BeadChip identified a locus on
      chromosome 12 from 36.8 to 38.6 Mb with 36 markers reaching genome-wide
      significance (P(genome) = 0.00001-0.026). This study suggests that a major locus
      on chromosome 12 harbors genetic variations affecting the development of
      intervertebral disc calcification in Dachshund.

PMID- 21846752
TI  - A suite of genetic markers useful in assessing wildcat (Felis silvestris ssp.)
      domestic cat (Felis silvestris catus) admixture.
AB  - The wildcat (Felis silvestris ssp.) is a conservation concern largely due to
      introgressive hybridization with its congener F. s. catus, the common domestic
      cat. Because of a recent divergence and entirely overlapping ranges,
      hybridization is common and pervasive between these taxa threatening the genetic
      integrity of remaining wildcat populations. Identifying pure wildcats for
      inclusion in conservation programs using current morphological discriminants is
      difficult because of gross similarity between them and the domestic, critically
      hampering conservation efforts. Here, we present a vetted panel of microsatellite
      loci and mitochondrial polymorphisms informative for each of the 5 naturally
      evolved wildcat subspecies and the derived domestic cat. We also present
      reference genotypes for each assignment class. Together, these marker sets and
      corresponding reference genotypes allow for the development of a genetic rational
      for defining "units of conservation" within a phylogenetically based taxonomy of
      the entire F. silvestris species complex. We anticipate this marker panel will
      allow conservators to assess genetic integrity and quantify admixture in managed
      wildcat populations and to be a starting point for more in-depth analysis of
      hybridization.

PMID- 21846753
TI  - The association of pericardial fat with coronary artery plaque index at MR
      imaging: The Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - PURPOSE: To determine the relationship of pericardial fat, which secretes
      proinflammatory markers that have been implicated in coronary atherosclerosis,
      with atherosclerotic plaque in an asymptomatic population-based cohort. MATERIALS
      AND METHODS: In this institutional review board-approved study, all participants
      supplied written informed consent. One hundred eighty-three participants (89
      women, 94 men; mean age, 61 years +/- 9 [standard deviation]) from the community
      based Multi-Ethnic Study of Atherosclerosis (MESA) were included. The coronary
      artery eccentricity (ratio of maximal to minimal coronary artery wall thickness)
      was determined by using magnetic resonance (MR) imaging and served as an index of
      plaque burden. The pericardial fat volume was determined by using computed
      tomography. Linear regression coefficient analysis was used to correlate
      pericardial fat volume with coronary artery wall thickness and plaque
      eccentricity. RESULTS: Pericardial fat volume correlated significantly with
      degree of plaque eccentricity (P < .05) in both men and women. After adjustments
      for body mass index (BMI) and waist circumference, traditional risk factors, C
      reactive protein level, and coronary artery calcium content, the relationship
      between pericardial fat and plaque eccentricity remained significant in men (P <
      .01) but not in women. BMI and waist circumference correlated with degree of
      plaque eccentricity in the univariate model (P < .05) but not after adjustment
      for pericardial fat volume or traditional risk factors. CONCLUSION: Pericardial
      fat volume, rather than BMI and waist circumference, was more strongly related to
      plaque eccentricity as a measure of coronary atherosclerotic plaque burden. The
      results support the proposed role of pericardial fat in association with
      atherosclerosis.

PMID- 21846754
TI  - Kidney injury molecule-1 and N-acetyl-beta-D-glucosaminidase in chronic heart
      failure: possible biomarkers of cardiorenal syndrome.
AB  - AIMS: Patients with chronic heart failure are often characterized by impaired
      renal function, also referred to as cardiorenal syndrome (CRS). The aim of this
      study was to assess whether novel markers of kidney injury are elevated in
      chronic heart failure and CRS. METHODS AND RESULTS: The new renal biomarkers
      kidney injury molecule-1 (KIM-1), N-acetyl-beta-d-glucosaminidase (NAG) and
      neutrophil gelatinase-associated lipocalin (NGAL) were assessed from urine
      samples of 173 individuals. Patients with chronic heart failure (n= 150) were
      characterized by decreased ejection fraction (32 +/- 9% vs. controls 62 +/- 4%, P
      < 0.001) and increased plasma N-terminal pro-brain natriuretic peptide (median
      1460 pg/mL, interquartile range (IQR) 630-3000 pg/mL vs. controls 56, IQR 25-64l
      pg/mL, P < 0.001). Urinary analysis showed that KIM-1 was significantly elevated
      in heart failure patients compared with healthy controls (1100, IQR 620-1920 vs.
      550, IQR 320-740 ng/g urinary creatinine, P < 0.001). Further, KIM-1 increased
      significantly with decreasing left ventricular function (r = -0.37, P < 0.001)
      and severity of New York Heart Association (NYHA)-class (r = 0.5, P < 0.001). N
      acetyl-beta-d-glucosaminidase showed a weaker response but correlated
      significantly with left ventricular dysfunction (r = -0.18, P= 0.015) and more
      severe clinical condition (r = 0.22, P= 0.04). In contrast, NGAL showed no
      significant correlation. Kidney injury molecule-1 and NAG were also predictors of
      all-cause mortality and the composite of all-cause mortality and
      rehospitalization for heart failure (all P < 0.05). CONCLUSIONS: Kidney injury
      molecule-1 and NAG are elevated in symptomatic heart failure. This finding may be
      present in patients with apparently normal kidney function and indicates tubular
      injury in chronic heart failure. Kidney injury molecule-1 and NAG are potential
      markers of CRS with additional prognostic value.

PMID- 21846755
TI  - Myocardial collagen turnover after surgical ventricular restoration in heart
      failure patients.
AB  - AIMS: Surgical ventricular restoration (SVR) aims to normalize left ventricular
      (LV) volume and shape in patients with ischaemic cardiomyopathy and anterior wall
      scar. The chronic effects on LV function may depend on alterations in myocardial
      collagen metabolism. The present study evaluated myocardial collagen synthesis
      and degradation rates at baseline and at 6 months follow-up after SVR. We
      hypothesize that the chronic effects of SVR on LV function and clinical outcome
      depend on alterations in myocardial collagen metabolism. METHODS AND RESULTS:
      Serum levels of aminoterminal propeptides of type I and III collagen (PINP,
      PIIINP), carboxyterminal telopeptide of type I collagen (ICTP), and tenascin-C
      (TNC) were measured at baseline and 6 months after SVR in 24 patients. In
      addition, New York Heart Association (NYHA) functional class, LV volumes and
      function were evaluated. At follow-up, a significant improvement in NYHA class
      (from 3.2 +/- 0.8 to 1.4 +/- 0.6, P< 0.001) and LV ejection fraction (from 28 +/-
      9 to 35 +/- 7%, P< 0.001) was found, whereas E/A ratio tended to increase (from
      1.4 +/- 1.1 to 1.9 +/- 1.1, P= 0.064). Serum levels of PINP, PIIINP, ICTP, and
      TNC increased significantly (PINP: from 37 +/- 15 to 67 +/- 26 MUg/L, P< 0.001;
      PIIINP: from 4.9 +/- 1.7 to 7.9 +/- 4.0 MUg/L, P< 0.001; ICTP: from 5.9 +/- 3.7
      to 10.0 +/- 5.3 MUg/L, P< 0.001; TNC: from 30 +/- 20 to 44 +/- 23 MUg/L, P=
      0.020). At follow-up, an LV ejection fraction <34% and E/A ratio >= 2.0 were
      significantly associated with increased serum levels of PIIINP and ICTP.
      CONCLUSION: In patients who underwent SVR, myocardial collagen metabolism was
      significantly enhanced 6 months after surgery. Serum levels of myocardial
      collagen turnover biomarkers were related to post-surgical LV systolic and
      diastolic function.

PMID- 21846756
TI  - Science to practice: are theranostic agents with encapsulated cells the key for
      diabetes therapy?
AB  - The transplantation of beta cells could be an effective therapy for diabetes,
      with much better stabilization of blood glucose levels than can be achieved with
      insulin injection. However, the therapeutic effect of these cell transplants
      usually lasts for a relatively short time owing to the strong immunologic
      reactions against the transplants. Protection from the immune system may be
      achieved by encapsulating the beta cells in such a way that their ability to
      release insulin is preserved. In the article of Arifi n and colleagues (1),
      encapsulated beta cells coembedded with DTDTPA (dithiolated
      diethylenetriaminepentaacetic acid) gadolinium- coated gold nanoparticles are
      suggested as a biohybrid theranostic transplant. The in vitro and in vivo data
      presented in the article give hope that these transplants have the potential to
      solve many of the problems associated with beta cell treatment of diabetes. In
      this context, the visibility of the transplanted cells at computed tomography
      (CT), magnetic resonance (MR) imaging, and ultrasonography (US) might give the
      physician additional fl exibility in monitoring the transplantation procedure and
      its effectiveness over time. Furthermore, other cellular therapies may benefi t
      from cellular encapsulation. The combination of imaging of the biohybrid
      transplants and noninvasive functional assessment is likely to further improve
      assessment of the viability and function of the transplanted cells.

PMID- 21846757
TI  - Mammographic screening and "overdiagnosis".

PMID- 21846758
TI  - Is mammographic screening justifiable considering its substantial overdiagnosis
      rate and minor effect on mortality?

PMID- 21846759
TI  - CT detection of pulmonary hypertension in interstitial lung disease: the glass is
      half full.

PMID- 21846760
TI  - Image-guided thermal ablation of lung malignancies.
AB  - Primary and secondary lung malignancies are often treated with surgery. Many
      patients are poor surgical candidates owing to advanced age or medical
      comorbidities. Alternatives to surgery for localized disease include radiation
      therapy and the newer treatments known as image-guided thermal ablation. Image
      guided thermal ablation involves the use of needlelike applicators that are
      placed directly into tumors by using imaging guidance. Tumors are destroyed by
      the application of either intense heat or cold. The specific ablative modalities
      of radiofrequency ablation, microwave ablation, laser ablation, and cryoablation
      are reviewed with respect to the various clinical indications for treatment of
      both primary and secondary lung malignancies.

PMID- 21846761
TI  - Detection of hemodynamically significant coronary artery stenosis: incremental
      diagnostic value of dynamic CT-based myocardial perfusion imaging.
AB  - PURPOSE: To determine the feasibility of computed tomography (CT)-based dynamic
      myocardial perfusion imaging for the detection of hemodynamically significant
      coronary artery stenosis, as defined with fractional flow reserve (FFR).
      MATERIALS AND METHODS: Institutional review board approval and informed patient
      consent were obtained before patient enrollment in the study. The study was HIPAA
      compliant. Subjects who were suspected of having or were known to have coronary
      artery disease underwent electrocardiographically triggered dynamic stress
      myocardial perfusion imaging. FFR measurement was performed within all main
      coronary arteries with a luminal narrowing of 50%-85%. Estimated myocardial blood
      flow (MBF) was derived from CT images by using a model-based parametric
      deconvolution method for 16 myocardial segments and was related to
      hemodynamically significant coronary artery stenosis with an FFR of 0.75 or less
      in a blinded fashion. Conventional measures of diagnostic accuracy were derived,
      and discriminatory power analysis was performed by using logistic regression
      analysis. RESULTS: Of 36 enrolled subjects, 33 (mean age, 68.1 years +/- 10
      [standard deviation]; 25 [76%] men, eight [24%] women) completed the study
      protocol. An MBF cut point of 75 mL/100 mL/min provided the highest
      discriminatory power (C statistic, 0.707; P <.001). While the diagnostic accuracy
      of CT for the detection of anatomically significant coronary artery stenosis
      (>50%) was high, it was low for the detection of hemodynamically significant
      stenosis (positive predictive value [PPV] per coronary segment, 49%; 95%
      confidence interval [CI]: 36%, 60%). With use of estimated MBF to reclassify
      lesions depicted with CT angiography, 30 of 70 (43%) coronary lesions were graded
      as not hemodynamically significant, which significantly increased PPV to 78% (95%
      CI: 61%, 89%; P = .02). The presence of a coronary artery stenosis with a
      corresponding MBF less than 75 mL/100 mL/min had a high risk for hemodynamic
      significance (odds ratio, 86.9; 95% CI:17.6, 430.4). CONCLUSION: Dynamic CT-based
      stress myocardial perfusion imaging may allow detection of hemodynamically
      significant coronary artery stenosis.

PMID- 21846762
TI  - Locally advanced rectal cancer: added value of diffusion-weighted MR imaging for
      predicting tumor clearance of the mesorectal fascia after neoadjuvant
      chemotherapy and radiation therapy.
AB  - PURPOSE: To evaluate the added value of diffusion-weighted (DW) imaging in
      combination with T2-weighted magnetic resonance (MR) imaging compared with T2
      weighted imaging alone for predicting tumor clearance of the mesorectal fascia
      (MRF) after neoadjuvant chemotherapy and radiation therapy (CRT) in patients with
      locally advanced rectal cancer. MATERIALS AND METHODS: This retrospective study
      was approved by the institutional review board, and informed consent was waived.
      Forty-five patients with rectal cancer with clinically suspected MRF invasion who
      underwent neoadjuvant CRT and subsequent surgery were enrolled. All patients
      underwent pre- and post-CRT 3.0-T rectal MR imaging with DW imaging. Two
      observers independently reviewed a set of T2-weighted images and a combined set
      of T2-weighted and DW images and rated them by using a five-point scale.
      Diagnostic performance was evaluated for each observer with receiver operating
      characteristic (ROC) curve analysis. Accuracy, sensitivity, specificity, positive
      predictive value, and negative predictive value (NPV) were assessed. The standard
      of reference was histopathologic findings in the surgical specimen. Pairwise
      comparison of the ROC curves was used to compare diagnostic performance between
      the two image sets; the McNemar test was used to compare accuracy, sensitivity,
      and specificity. RESULTS: The diagnostic performance (area under the ROC curve
      [A(z)]) with respect to MRF tumor clearance of both observers improved
      significantly after additional review of DW images: A(z) improved from 0.770 to
      0.918 (P = .017) for observer 1 and from 0.847 to 0.960 (P = .026) for observer
      2. The diagnostic accuracy of DW combined with T2-weighted imaging (observer 1,
      89% [40 of 45]; observer 2, 93% [42 of 45]), sensitivity (observer 1, 94% [31 of
      33]; observer 2, 97% [32 of 33]) and NPV (observer 1, 82% [nine of 11]; observer
      2, 91% [10 of 11]) were significantly higher than those of T2-weighted imaging
      alone (accuracy: observer 1, 40% [18 of 45], P < .001; observer 2, 69% [31 of
      45], P = .022; sensitivity: observer 1, 21% [seven of 33], P < .001; observer 2,
      67% [22 of 33], P = .002; NPV: observer 1, 30% [11 of 37], P = .013; observer 2,
      45% [nine of 20], P = .025). Interobserver agreement of confidence levels was
      fair for T2-weighted imaging alone (kappa = 0.212) but was excellent for the
      combined set of DW and T2-weighted images (kappa = 0.880). CONCLUSION: Adding DW
      imaging to T2-weighted imaging can improve the prediction of tumor clearance in
      the MRF after neoadjuvant CRT compared with T2-weighted imaging alone in patients
      with locally advanced rectal cancer.

PMID- 21846764
TI  - Case 173: acute disseminated encephalomyelitis confined to the brainstem.

PMID- 21846765
TI  - Adverse reactions during gadoteridol-enhanced MR imaging.

PMID- 21846766
TI  - Virtual monochromatic spectral imaging with fast kilovoltage switching should not
      be used as standard CT imaging modality.

PMID- 21846767
TI  - Direct costs and cost-effectiveness of dual-source computed tomography and
      invasive coronary angiography in patients with an intermediate pretest likelihood
      for coronary artery disease.
AB  - AIMS: The study aims to determine the direct costs and comparative cost
      effectiveness of latest-generation dual-source computed tomography (DSCT) and
      invasive coronary angiography for diagnosing coronary artery disease (CAD) in
      patients suspected of having this disease. METHODS: The study was based on a
      previously elaborated cohort with an intermediate pretest likelihood for CAD and
      on complementary clinical data. Cost calculations were based on a detailed
      analysis of direct costs, and generally accepted accounting principles were
      applied. Based on Bayes' theorem, a mathematical model was used to compare the
      cost-effectiveness of both diagnostic approaches. Total costs included direct
      costs, induced costs and costs of complications. Effectiveness was defined as the
      ability of a diagnostic test to accurately identify a patient with CAD. RESULTS:
      Direct costs amounted to ?98.60 for DSCT and to ?317.75 for invasive coronary
      angiography. Analysis of model calculations indicated that cost-effectiveness
      grew hyperbolically with increasing prevalence of CAD. Given the prevalence of
      CAD in the study cohort (24%), DSCT was found to be more cost-effective than
      invasive coronary angiography (?970 vs ?1354 for one patient correctly diagnosed
      as having CAD). At a disease prevalence of 49%, DSCT and invasive angiography
      were equally effective with costs of ?633. Above a threshold value of disease
      prevalence of 55%, proceeding directly to invasive coronary angiography was more
      cost-effective than DSCT. CONCLUSIONS: With proper patient selection and
      consideration of disease prevalence, DSCT coronary angiography is cost-effective
      for diagnosing CAD in patients with an intermediate pretest likelihood for it.
      However, the range of eligible patients may be smaller than previously reported.

PMID- 21846768
TI  - Acute aortic dissection after balloon angioplasty of a recoarctation and
      treatment by stenting and distal membrane fenestration in a child.

PMID- 21846769
TI  - Structures and processes of care in ambulatory oncology settings and nurse
      reported exposure to chemotherapy.
AB  - PURPOSE: Oncology nurses in ambulatory settings are at increased risk for
      unintentional chemotherapy exposure due to the large volumes of agents delivered
      and the absence of regulatory enforcement. Given the limited data regarding the
      correlates of exposure, the authors sought to identify the relationship between
      the organisational structures and processes of care in ambulatory oncology
      settings associated with increased risk of unintentional chemotherapy. METHODS:
      Between April 2010 and June 2010, a state-wide sample of oncology nurses were
      surveyed who reported their employment outside of hospital inpatient units
      (n=1339). The survey examined the likelihood of self-reported exposure to
      chemotherapy as a function of perceived quality of the practice environment,
      nursing workload, and seven ambulatory chemotherapy administration safety
      standards. RESULTS: The response rate was 30.4%, with minimal demographic
      differences observed between respondents and non-respondents. The overall rate of
      exposure to the skin or eyes in the past year was 16.9%. In multivariable
      logistic regression models that controlled for demographic characteristics and
      clustering of nurses in practices, the likelihood of exposure decreased when
      nurses reported adequate staffing and resources (OR 0.35, 95% CI 0.17 to 0.73;
      p=0.001), and when nurses reported that chemotherapy doses were verified by two
      nurses frequently or very frequently (OR 0.17, 95% CI 0.05 to 0.59; p=0.001).
      CONCLUSIONS: Oncology nurses in the ambulatory setting report substantial
      unintentional skin and eye exposure to chemotherapy. Ensuring adequate staffing
      and resources and adherence to recognised practice standards may protect oncology
      nurses from harm.

PMID- 21846771
TI  - A coarse-grained force field for Protein-RNA docking.
AB  - The awareness of important biological role played by functional, non coding (nc)
      RNA has grown tremendously in recent years. To perform their tasks, ncRNA
      molecules typically unite with protein partners, forming ribonucleoprotein
      complexes. Structural insight into their architectures can be greatly
      supplemented by computational docking techniques, as they provide means for the
      integration and refinement of experimental data that is often limited to
      fragments of larger assemblies or represents multiple levels of spatial
      resolution. Here, we present a coarse-grained force field for protein-RNA
      docking, implemented within the framework of the ATTRACT program. Complex
      structure prediction is based on energy minimization in rotational and
      translational degrees of freedom of binding partners, with possible extension to
      include structural flexibility. The coarse-grained representation allows for fast
      and efficient systematic docking search without any prior knowledge about complex
      geometry.

PMID- 21846770
TI  - The DEAH-box RNA helicase RHAU binds an intramolecular RNA G-quadruplex in TERC
      and associates with telomerase holoenzyme.
AB  - Guanine-quadruplexes (G4) consist of non-canonical four-stranded helical
      arrangements of guanine-rich nucleic acid sequences. The bulky and
      thermodynamically stable features of G4 structures have been shown in many
      respects to affect normal nucleic acid metabolism. In vivo conversion of G4
      structures to single-stranded nucleic acid requires specialized proteins with G4
      destabilizing/unwinding activity. RHAU is a human DEAH-box RNA helicase that
      exhibits G4-RNA binding and resolving activity. In this study, we employed RIP
      chip analysis to identify en masse RNAs associated with RHAU in vivo.
      Approximately 100 RNAs were found to be associated with RHAU and bioinformatics
      analysis revealed that the majority contained potential G4-forming sequences.
      Among the most abundant RNAs selectively enriched with RHAU, we identified the
      human telomerase RNA template TERC as a true target of RHAU. Remarkably, binding
      of RHAU to TERC depended on the presence of a stable G4 structure in the 5'
      region of TERC, both in vivo and in vitro. RHAU was further found to associate
      with the telomerase holoenzyme via the 5'-region of TERC. Collectively, these
      results provide the first evidence that intramolecular G4-RNAs serve as
      physiologically relevant targets for RHAU. Furthermore, our results suggest the
      existence of alternatively folded forms of TERC in the fully assembled telomerase
      holoenyzme.

PMID- 21846772
TI  - The downstream atpE cistron is efficiently translated via its own cis-element in
      partially overlapping atpB-atpE dicistronic mRNAs in chloroplasts.
AB  - The chloroplast atpB and atpE genes encode subunits beta and epsilon of the ATP
      synthase, respectively. They are co-transcribed as dicistronic mRNAs in flowering
      plants. An unusual feature is an overlap (AUGA) of the atpB stop codon (UGA) with
      the atpE start codon (AUG). Hence, atpE translation has been believed to depend
      on atpB translation (i.e. translational coupling). Using an in vitro translation
      system from tobacco chloroplasts, we showed that both atpB and atpE cistrons are
      translated from the tobacco dicistronic mRNA, and that the efficiency of atpB
      translation is higher than that of atpE translation. When the atpB 5'-UTR was
      replaced with lower efficiency 5'-UTRs, atpE translation was higher than atpB
      translation. Removal of the entire atpB 5'-UTR arrested atpB translation but atpE
      translation still proceeded. Introduction of a premature stop codon in the atpB
      cistron did not abolish atpE translation. These results indicate that atpE
      translation is independent of atpB translation. Mutation analysis showed that the
      atpE cistron possesses its own cis-element(s) for translation, located ~25 nt
      upstream from the start codon.

PMID- 21846773
TI  - Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation
      independent context.
AB  - Mammalian DNA methyltransferase 1 (DNMT1) is essential for maintaining DNA
      methylation patterns after cell division. Disruption of DNMT1 catalytic activity
      results in whole genome cytosine demethylation of CpG dinucleotides, promoting
      severe dysfunctions in somatic cells and during embryonic development. While
      these observations indicate that DNMT1-dependent DNA methylation is required for
      proper cell function, the possibility that DNMT1 has a role independent of its
      catalytic activity is a matter of controversy. Here, we provide evidence that
      DNMT1 can support cell functions that do not require the C-terminal catalytic
      domain. We report that PCNA and DMAP1 domains in the N-terminal region of DNMT1
      are sufficient to modulate E-cadherin expression in the absence of noticeable
      changes in DNA methylation patterns in the gene promoters involved. Changes in E
      cadherin expression are directly associated with regulation of beta-catenin
      dependent transcription. Present evidence suggests that the DNMT1 acts on E
      cadherin expression through its direct interaction with the E-cadherin
      transcriptional repressor SNAIL1.

PMID- 21846774
TI  - Selective requirement of H2B N-Terminal tail for p14ARF-induced chromatin
      silencing.
AB  - The N-terminal tail of histone H2B is believed to be involved in gene silencing,
      but how it exerts its function remains elusive. Here, we report the biochemical
      characterization of p14ARF tumor suppressor as a transcriptional repressor that
      selectively recognizes the unacetylated H2B tails on nucleosomes. The p14ARF-H2B
      tail interaction is functional, as the antagonistic effect of p14ARF on chromatin
      transcription is lost upon deletion or acetylation of H2B tails. Gene expression
      profiling and chromatin immunoprecipitation studies emphasize the significance of
      H2B deacetylation and p14ARF recruitment in establishing a repressive environment
      over the cell cycle regulatory genes. Moreover, HDAC1-mediated H2B deacetylation,
      especially at K20, constitutes an essential step in tethering p14ARF near target
      promoters. Our results thus reveal a hitherto unknown role of p14ARF in the
      regulation of chromatin transcription, as well as molecular mechanisms governing
      the repressive action of p14ARF.

PMID- 21846775
TI  - Cleavage of intron from the standard or non-standard position of the precursor
      tRNA by the splicing endonuclease of Aeropyrum pernix, a hyper-thermophilic
      Crenarchaeon, involves a novel RNA recognition site in the Crenarchaea specific
      loop.
AB  - In Crenarchaea, several tRNA genes are predicted to express precursor-tRNAs (pre
      tRNAs) with canonical or non-canonical introns at various positions. We initially
      focused on the tRNA(Thr) species of hyperthermophilic crenarchaeon, Aeropyrum
      pernix (APE) and found that in the living APE cells three tRNA(Thr) species were
      transcribed and subsequently matured to functional tRNAs. During maturation,
      introns in two of them were cleaved from standard and non-standard positions.
      Biochemical studies revealed that the APE splicing endonuclease (APE-EndA)
      removed both types of introns, including the non-canonical introns, without any
      nucleotide modification. To clarify the underlying reasons for broad substrate
      specificity of APE-EndA, we determined the crystal structure of wild-type APE
      EndA and subsequently compared its structure with that of Archaeaoglobus fulgidus
      (AFU)-EndA, which has narrow substrate specificity. Remarkably, structural
      comparison revealed that APE-EndA possesses a Crenarchaea specific loop (CSL).
      Introduction of CSL into AFU-EndA enhanced its intron-cleaving activity
      irrespective of the position or motif of the intron. Thus, our biochemical and
      crystallographic analyses of the chimera-EndA demonstrated that the CSL is
      responsible for the broad substrate specificity of APE-EndA. Furthermore,
      mutagenesis studies revealed that Lys44 in CSL functions as the RNA recognition
      site.

PMID- 21846777
TI  - A systematic review of longitudinal population-based studies on the predictors of
      smoking cessation in adolescent and young adult smokers.
AB  - OBJECTIVE: To describe the determinants of self-initiated smoking cessation of
      duration of at least 6 months as identified in longitudinal population-based
      studies of adolescent and young adult smokers. METHODS: A systematic search of
      the PubMed and EMBASE databases using smoking, tobacco, cessation, quit and stop
      as keywords was performed. Limits included articles related to humans, in
      English, published between January 1984 and August 2010, and study population
      aged 10-29 years. A total of 4502 titles and 871 abstracts were reviewed
      independently by 2 and 3 reviewers, respectively. Nine articles were retained for
      data abstraction. Data on study location, timeframe, duration of follow-up,
      number of data collection points, sample size, age/grade of participants, number
      of quitters, smoking status at baseline, definition of cessation, covariates and
      analytic method were abstracted from each article. The number of studies that
      reported a statistically significant association between each determinant
      investigated and cessation were tabulated, from among all studies that assessed
      the determinant. RESULTS: Despite heterogeneity in methods across studies, five
      factors robustly predicted quitting across studies in which the factor was
      investigated: not having friends who smoke, not having intentions to smoke in the
      future, resisting peer pressure to smoke, being older at first use of cigarette
      and having negative beliefs about smoking. CONCLUSIONS: The literature on
      longitudinal predictors of cessation in adolescent and young adult smokers is not
      well developed. Cessation interventions for this population will remain less than
      optimally effective until there is a solid evidence base on which to develop
      interventions.

PMID- 21846776
TI  - Nuclear hormone 1alpha,25-dihydroxyvitamin D3 elicits a genome-wide shift in the
      locations of VDR chromatin occupancy.
AB  - A global understanding of the actions of the nuclear hormone 1alpha,25
      dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) and its vitamin D receptor (VDR)
      requires a genome-wide analysis of VDR binding sites. In THP-1 human monocytic
      leukemia cells we identified by ChIP-seq 2340 VDR binding locations, of which
      1171 and 520 occurred uniquely with and without 1alpha,25(OH)(2)D(3) treatment,
      respectively, while 649 were common. De novo identified direct repeat spaced by 3
      nucleotides (DR3)-type response elements (REs) were strongly associated with the
      ligand-responsiveness of VDR occupation. Only 20% of the VDR peaks diminishing
      most after ligand treatment have a DR3-type RE, in contrast to 90% for the most
      growing peaks. Ligand treatment revealed 638 1alpha,25(OH)(2)D(3) target genes
      enriched in gene ontology categories associated with immunity and signaling. From
      the 408 upregulated genes, 72% showed VDR binding within 400 kb of their
      transcription start sites (TSSs), while this applied only for 43% of the 230
      downregulated genes. The VDR loci showed considerable variation in gene
      regulatory scenarios ranging from a single VDR location near the target gene TSS
      to very complex clusters of multiple VDR locations and target genes. In
      conclusion, ligand binding shifts the locations of VDR occupation to DR3-type REs
      that surround its target genes and occur in a large variety of regulatory
      constellations.

PMID- 21846778
TI  - Search terms and a validated brief search filter to retrieve publications on
      health-related values in Medline: a word frequency analysis study.
AB  - OBJECTIVE: Healthcare debates and policy developments are increasingly concerned
      with a broad range of values-related areas. These include not only ethical,
      moral, religious, and other types of values 'proper', but also beliefs,
      preferences, experiences, choices, satisfaction, quality of life, etc. Research
      on such issues may be difficult to retrieve. This study used word frequency
      analysis to generate a broad pool of search terms and a brief filter to
      facilitate relevant searches in bibliographic databases. METHODS: Word frequency
      analysis for 'values terms' was performed on citations on diabetes, obesity,
      dementia, and schizophrenia (Medline; 2004-2006; 4440 citations; 1,110,291
      words). Concordance(r) and SPSS 14.0 were used. Text words and MeSH terms of high
      frequency and precision were compiled into a search filter. It was validated on
      datasets of citations on dentistry and food hypersensitivity. RESULTS: 144 unique
      text words and 124 unique MeSH terms of moderate and high frequency (>= 20) and
      very high precision (>= 90%) were identified. Of these, 19 text words and seven
      MeSH terms were compiled into a 'brief values filter'. In the derivation dataset,
      it had a sensitivity of 76.8% and precision of 86.8%. In the validation datasets,
      its sensitivity and precision were, respectively, 70.1% and 63.6% (food
      hypersensitivity) and 47.1% and 82.6% (dentistry). CONCLUSIONS: This study
      provided a varied pool of search terms and a simple and highly effective tool for
      retrieving publications on health-related values. Further work is required to
      facilitate access to such research and enhance its chances of being translated
      into practice, policy, and service improvements.

PMID- 21846779
TI  - Building better guidelines with BRIDGE-Wiz: development and evaluation of a
      software assistant to promote clarity, transparency, and implementability.
AB  - OBJECTIVE: To demonstrate the feasibility of capturing the knowledge required to
      create guideline recommendations in a systematic, structured, manner using a
      software assistant. Practice guidelines constitute an important modality that can
      reduce the delivery of inappropriate care and support the introduction of new
      knowledge into clinical practice. However, many guideline recommendations are
      vague and underspecified, lack any linkage to supporting evidence or
      documentation of how they were developed, and prove to be difficult to transform
      into systems that influence the behavior of care providers. METHODS: The BRIDGE
      Wiz application (Building Recommendations In a Developer's Guideline Editor) uses
      a wizard approach to address the questions: (1) under what circumstances? (2)
      who? (3) ought (with what level of obligation?) (4) to do what? (5) to whom? (6)
      how and why? Controlled natural language was applied to create and populate a
      template for recommendation statements. RESULTS: The application was used by five
      national panels to develop guidelines. In general, panelists agreed that the
      software helped to formalize a process for authoring guideline recommendations
      and deemed the application usable and useful. DISCUSSION: Use of BRIDGE-Wiz
      promotes clarity of recommendations by limiting verb choices, building active
      voice recommendations, incorporating decidability and executability checks, and
      limiting Boolean connectors. It enhances transparency by incorporating systematic
      appraisal of evidence quality, benefits, and harms. BRIDGE-Wiz promotes
      implementability by providing a pseudocode rule, suggesting deontic modals, and
      limiting the use of 'consider'. CONCLUSION: Users found that BRIDGE-Wiz
      facilitates the development of clear, transparent, and implementable guideline
      recommendations.

PMID- 21846780
TI  - Same organization, same electronic health records (EHRs) system, different use:
      exploring the linkage between practice member communication patterns and EHR use
      patterns in an ambulatory care setting.
AB  - OBJECTIVE: Despite efforts made by ambulatory care organizations to standardize
      the use of electronic health records (EHRs), practices often incorporate these
      systems into their work differently from each other. One potential factor
      contributing to these differences is within-practice communication patterns. The
      authors explore the linkage between within-practice communication patterns and
      practice-level EHR use patterns. DESIGN: Qualitative study of six practices
      operating within the same multi-specialty ambulatory care organization using the
      same EHR system. Semistructured interviews and direct observation were conducted
      with all physicians, nurses, medical assistants, practice managers, and non
      clinical staff from each practice. MEASUREMENTS: An existing model of practice
      relationships was used to analyze communication patterns within the practices.
      Practice-level EHR use was defined and analyzed as the ways in which a practice
      uses an EHR as a collective or a group-including the degree of feature use, level
      of EHR-enabled communication, and frequency that EHR use changes in a practice.
      Interview and observation data were analyzed for themes. Based on these themes,
      within-practice communication patterns were categorized as fragmented or
      cohesive, and practice-level EHR use patterns were categorized as heterogeneous
      or homogeneous. Practices where EHR use was uniformly high across all users were
      further categorized as having standardized EHR use. Communication patterns and
      EHR use patterns were compared across the six practices. RESULTS: Within-practice
      communication patterns were associated with practice-level EHR use patterns. In
      practices where communication patterns were fragmented, EHR use was
      heterogeneous. In practices where communication patterns were cohesive, EHR use
      was homogeneous. Additional analysis revealed that practices that had achieved
      standardized EHR use (uniformly high EHR use across all users) exhibited high
      levels of mindfulness and respectful interaction, whereas practices that were
      furthest from achieving standardized EHR use exhibited low levels of mindfulness
      and respectful interaction. CONCLUSION: Within-practice communication patterns
      provide a unique perspective for exploring the issue of standardization in EHR
      use. A major fallacy of setting homogeneous EHR use as the goal for practice
      level EHR use is that practices with uniformly low EHR use could be considered
      successful. Achieving uniformly high EHR use across all users in a practice is
      more consistent with the goals of current EHR adoption and use efforts. It was
      found that some communication patterns among practice members may enable more
      standardized EHR use than others. Understanding the linkage between communication
      patterns and EHR use can inform understanding of the human element in EHR use and
      may provide key lessons for the implementation of EHRs and other health
      information technologies.

PMID- 21846781
TI  - Anti-inflammatory lactobacilli: strain specificity.

PMID- 21846782
TI  - Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong
      Kong Chinese: a population study using proton-magnetic resonance spectroscopy and
      transient elastography.
AB  - OBJECTIVE: Knowledge of the epidemiology of non-alcoholic fatty liver disease
      (NAFLD) is incomplete because liver biopsy cannot be performed on the general
      population to assess disease severity. New non-invasive tests allow accurate and
      safe assessment in healthy individuals. The aim of this study was to examine the
      prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese
      population. METHODS: Subjects were recruited from the community by random
      selection from the government census database. Liver fat and fibrosis were
      assessed by proton-magnetic resonance spectroscopy and transient elastography,
      respectively. RESULTS: Overall, 264 of 922 (28.6%) subjects had intrahepatic
      triglyceride content >=5%. Excluding 12 subjects with significant alcohol
      consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to
      30.2%). Each component of the metabolic syndrome increased the risk of fatty
      liver in a dose-dependent manner (prevalence of 4.5% in subjects without any
      component and 80.0% in those with all five components). 8 (3.7%) patients with
      fatty liver had liver stiffness >=9.6 kPa, a level suggestive of advanced
      fibrosis. Body mass index and alanine aminotransferase level were independent
      factors associated with liver stiffness. Together with other clinical prediction
      scores, the estimated prevalence of advanced fibrosis in patients with fatty
      liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10
      g per day) did not have higher risk of fatty liver after adjustment for
      demographic and metabolic factors. The liver stiffness was 4.7+/-1.9 kPa in
      modest drinkers and 4.6+/-1.7 kPa in non-drinkers (p=0.54). CONCLUSION: NAFLD is
      found in over a quarter of the general adult Chinese population, but the
      proportion of patients with advanced fibrosis is low. Modest alcohol consumption
      does not increase the risk of fatty liver or liver fibrosis.

PMID- 21846783
TI  - Evidence for accelerated colorectal adenoma--carcinoma progression in MUTYH
      associated polyposis?
AB  - BACKGROUND AND AIM: MUTYH-associated polyposis (MAP) is an autosomal recessive
      inherited disorder characterised by the development of polyposis in the upper and
      lower gastrointestinal tract and a high risk of colorectal cancer (CRC). We
      evaluated the natural history of the disease and the outcome of colorectal
      surveillance and management. METHODS: A large Western European dataset of
      biallelic MUTYH mutation carriers comprising 254 patients was used. Detailed
      information was collected on polyp and cancer development in the colorectum, and
      the outcome of surveillance and surgery. Survival methods were used to calculate
      the risk of CRC development. RESULTS: The mean follow-up was 9.8 years.
      Colorectal polyposis was diagnosed at a mean age of 44.8 years (range: 12-77
      years). Most patients had <100 colorectal adenomas at diagnosis. CRC was
      diagnosed in 147 (58%) of the 254 patients (mean age at diagnosis: 48.5, range:
      21-77 years). The cumulative lifetime risk of CRC was 63% at age 60 years. There
      was no correlation between the number of adenomas and the presence of CRC. The
      cumulative risk of CRC in patients presenting with polyps was 9% after 5 years of
      follow-up. Patients presenting with CRC had 11% risk of developing a metachronous
      CRC at 5 years after surgery. Thirty-seven per cent of patients with MAP with CRC
      who underwent partial colonic resection needed secondary surgery shortly
      afterwards. CONCLUSIONS: The high risk of developing CRC under surveillance in
      patients with MAP may suggest an accelerated carcinogenesis. Surveillance of
      these patients should therefore include colonoscopy at short intervals, for
      example, at 1-2-year intervals starting from the age of 18 to 20 years. If
      surgery for CRC is warranted, a (sub)total colectomy is recommended.

PMID- 21846784
TI  - Realizing the full potential of electronic health records: the role of natural
      language processing.

PMID- 21846785
TI  - Overcoming barriers to NLP for clinical text: the role of shared tasks and the
      need for additional creative solutions.

PMID- 21846786
TI  - Natural language processing: an introduction.
AB  - OBJECTIVES: To provide an overview and tutorial of natural language processing
      (NLP) and modern NLP-system design. TARGET AUDIENCE: This tutorial targets the
      medical informatics generalist who has limited acquaintance with the principles
      behind NLP and/or limited knowledge of the current state of the art. SCOPE: We
      describe the historical evolution of NLP, and summarize common NLP sub-problems
      in this extensive field. We then provide a synopsis of selected highlights of
      medical NLP efforts. After providing a brief description of common machine
      learning approaches that are being used for diverse NLP sub-problems, we discuss
      how modern NLP architectures are designed, with a summary of the Apache
      Foundation's Unstructured Information Management Architecture. We finally
      consider possible future directions for NLP, and reflect on the possible impact
      of IBM Watson on the medical field.

PMID- 21846787
TI  - Automatic extraction of relations between medical concepts in clinical texts.
AB  - OBJECTIVE: A supervised machine learning approach to discover relations between
      medical problems, treatments, and tests mentioned in electronic medical records.
      MATERIALS AND METHODS: A single support vector machine classifier was used to
      identify relations between concepts and to assign their semantic type. Several
      resources such as Wikipedia, WordNet, General Inquirer, and a relation similarity
      metric inform the classifier. RESULTS: The techniques reported in this paper were
      evaluated in the 2010 i2b2 Challenge and obtained the highest F1 score for the
      relation extraction task. When gold standard data for concepts and assertions
      were available, F1 was 73.7, precision was 72.0, and recall was 75.3. F1 is
      defined as 2*Precision*Recall/(Precision+Recall). Alternatively, when concepts
      and assertions were discovered automatically, F1 was 48.4, precision was 57.6,
      and recall was 41.7. DISCUSSION: Although a rich set of features was developed
      for the classifiers presented in this paper, little knowledge mining was
      performed from medical ontologies such as those found in UMLS. Future studies
      should incorporate features extracted from such knowledge sources, which we
      expect to further improve the results. Moreover, each relation discovery was
      treated independently. Joint classification of relations may further improve the
      quality of results. Also, joint learning of the discovery of concepts,
      assertions, and relations may also improve the results of automatic relation
      extraction. CONCLUSION: Lexical and contextual features proved to be very
      important in relation extraction from medical texts. When they are not available
      to the classifier, the F1 score decreases by 3.7%. In addition, features based on
      similarity contribute to a decrease of 1.1% when they are not available.

PMID- 21846788
TI  - Health information exchange usage in emergency departments and clinics: the who,
      what, and why.
AB  - OBJECTIVE: Health information exchange (HIE) systems are being developed across
      the nation. Understanding approaches taken by existing successful exchanges can
      help new exchange efforts determine goals and plan implementations. The goal of
      this study was to explore characteristics of use and users of a successful
      regional HIE. DESIGN: We used a mixed-method analysis, consisting of cross
      sectional audit log data, semi-structured interviews, and direct observation in a
      sample of emergency departments and ambulatory safety net clinics actively using
      HIE. For each site, we measured overall usage trends, user logon statistics, and
      data types accessed by users. We also assessed reasons for use and outcomes of
      use. RESULTS: Overall, users accessed HIE for 6.8% of all encounters, with higher
      rates of access for repeat visits, for patients with comorbidities, for patients
      known to have data in the exchange, and at sites providing HIE access to both
      nurses and physicians. Discharge summaries and test reports were the most
      frequently accessed data in the exchange. Providers consistently noted retrieving
      additional history, preventing repeat tests, comparing new results to retrieved
      results, and avoiding hospitalizations as a consequence of HIE access.
      CONCLUSION: HIE use in emergency departments and ambulatory clinics was focused
      on patients where missing information was believed to be present in the exchange
      and was related to factors including the roles of people with access, the
      setting, and other site-specific issues that impacted the overall breadth of
      routine system use. These data should form an important foundation as other sites
      embark upon HIE implementation.

PMID- 21846790
TI  - Designing and implementing a COPD discharge care bundle.
AB  - National surveys have revealed significant differences in patient outcomes
      following admission to hospital with acute exacerbation of COPD which are likely
      to be due to variations in care. We developed a care bundle, comprising a short
      list of evidence-based practices to be implemented prior to discharge for all
      patients admitted with this condition, based on a review of national guidelines
      and other relevant literature, expert opinion and patient consultation.
      Implementation was then piloted using action research methodologies with patient
      input. Actively involving staff was vital to ensure that the changes introduced
      were understood and the process followed. Implementation of a care bundle has the
      potential to produce a dramatic improvement in compliance with optimum health
      care practice.

PMID- 21846791
TI  - Isolation and characterization of 19 new microsatellite loci in Colocasia
      esculenta (Araceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for taro (Colocasia
      esculenta) to investigate its population genetics and evolutionary history
      through germplasm improvement. * METHODS AND RESULTS: Nineteen microsatellite
      loci were identified in three populations. The number of alleles per locus ranged
      from two to seven, with a mean of 4.68. The observed and expected
      heterozygosities ranged from 0.231 to 0.820 and from 0.126 to 0.742,
      respectively. * CONCLUSIONS: These new genetic markers will be useful for the
      study of taro germplasm management and population evolution in southwestern
      China.

PMID- 21846792
TI  - Resistance and tolerance to herbivory in Solidago altissima (Asteraceae): genetic
      variability, costs, and selection for multiple traits.
AB  - PREMISE OF THE STUDY: Quantifying the genetic variability, fitness costs, and
      selection gradients associated with plant defense traits is necessary to
      understand their evolution and continued persistence in populations. Few studies
      have simultaneously examined the costs, benefits, and genetic variability in
      multiple traits related to plant resistance and tolerance to herbivory. *
      METHODS: Using 103 Solidago altissima (Asteraceae) genets from two populations
      previously studied in situ, we conducted a common garden experiment to assess
      genetic variability, costs, selection gradients, and correlations among
      resistance, tolerance, and various resistance and tolerance traits (i.e., lateral
      branching, relative growth rate, leaf addition and senescence rate, specific leaf
      area, and leaf toughness). * KEY RESULTS: We report evidence for significant
      genetic variability in resistance and various tolerance-related traits but low
      broad-sense heritability (H(2) < 0.14) for all traits. For all traits examined,
      no correlation existed between trait levels of parent ramets (measured in their
      field of origin) and daughter ramets (measured in the common garden), suggesting
      plasticity in goldenrod traits. We found a strong cost of resistance and
      selection gradient against high resistance. Conversely, we found no evidence of
      costs but did find significant selection gradients favoring increased tolerance
      and many tolerance trait levels. * CONCLUSIONS: Our study suggests that
      herbivores impose selection favoring increased tolerance and reduced resistance
      in goldenrods. In this environment, we expect that over time, resistant genets
      will decrease in frequency. Despite strong selection pressures, the evolution of
      tolerance in this environment may be constrained by the low broad-sense
      heritability in tolerance traits.

PMID- 21846793
TI  - Elevated levels of active matrix metalloproteinase-9 cause hypertrophy in
      skeletal muscle of normal and dystrophin-deficient mdx mice.
AB  - Matrix metalloproteinases (MMPs) are a group of extracellular proteases involved
      in tissue remodeling in several physiological and pathophysiological conditions.
      While increased expression of MMPs (especially MMP-9) has been observed in
      skeletal muscle in numerous conditions, their physiological significance remains
      less-well understood. By generating novel skeletal muscle-specific transgenic
      (Tg) mice expressing constitutively active mutant of MMP-9 (i.e. MMP-9G100L), in
      this study, we have investigated the effects of elevated levels of MMP-9 on
      skeletal muscle structure and function in vivo. Tg expression of enzymatically
      active MMP-9 protein significantly increased skeletal muscle fiber cross-section
      area, levels of contractile proteins and force production in isometric
      contractions. MMP-9 stimulated the activation of the Akt signaling pathway in Tg
      mice. Moreover, expression of active MMP-9 increased the proportion of fast-type
      fiber in soleus muscle of mice. Overexpression of MMP-9 also considerably reduced
      the deposition of collagens I and IV in skeletal muscle in vivo. In one-year-old
      mdx mice (a model for Duchenne muscular dystrophy, DMD), deletion of the Mmp9
      gene reduced fiber hypertrophy and phosphorylation of Akt and p38 mitogen
      activated protein kinase. Collectively, our study suggests that elevated levels
      of active MMP-9 protein cause hypertrophy in skeletal muscle and that the
      modulation of MMP-9 levels may have therapeutic value in various muscular
      disorders including DMD.

PMID- 21846794
TI  - Analysis of alternative splicing associated with aging and neurodegeneration in
      the human brain.
AB  - Age is the most important risk factor for neurodegeneration; however, the effects
      of aging and neurodegeneration on gene expression in the human brain have most
      often been studied separately. Here, we analyzed changes in transcript levels and
      alternative splicing in the temporal cortex of individuals of different ages who
      were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or
      affected by Alzheimer's disease (AD). We identified age-related splicing changes
      in cognitively normal individuals and found that these were present also in 95%
      of individuals with FTLD or AD, independent of their age. These changes were
      consistent with increased polypyrimidine tract binding protein (PTB)-dependent
      splicing activity. We also identified disease-specific splicing changes that were
      present in individuals with FTLD or AD, but not in cognitively normal
      individuals. These changes were consistent with the decreased neuro-oncological
      ventral antigen (NOVA)-dependent splicing regulation, and the decreased nuclear
      abundance of NOVA proteins. As expected, a dramatic down-regulation of neuronal
      genes was associated with disease, whereas a modest down-regulation of glial and
      neuronal genes was associated with aging. Whereas our data indicated that the age
      related splicing changes are regulated independently of transcript-level changes,
      these two regulatory mechanisms affected expression of genes with similar
      functions, including metabolism and DNA repair. In conclusion, the alternative
      splicing changes identified in this study provide a new link between aging and
      neurodegeneration.

PMID- 21846795
TI  - Red wine consumption is inversely associated with 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine-DNA adduct levels in prostate.
AB  - In humans, genetic variation and dietary factors may alter the biological effects
      of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the
      major heterocyclic amines generated from cooking meats at high temperatures that
      has carcinogenic potential through the formation of DNA adducts. Previously, we
      reported grilled red meat consumption associated with PhIP-DNA adduct levels in
      human prostate. In this study, we expanded our investigation to estimate the
      associations between beverage consumption and PhIP-DNA adduct levels in prostate
      for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption
      had the strongest association with PhIP-DNA adduct levels showing an inverse
      correlation in both tumor (P = 0.006) and nontumor (P = 0.002) prostate cells.
      Red wine consumption was significantly lower in African American compared with
      white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In
      African Americans compared with whites, however, associations between red wine
      consumption and PhIP-DNA adduct levels were not as strong as associations with
      specific (e.g., SULT1A1 and UGT1A10 genotypes) and nonspecific (e.g., African
      ancestry) genetic variation. In a multivariable model, the covariate for red wine
      consumption explained a comparable percentage (13%-16%) of the variation in PhIP
      DNA adduct levels in prostate across the two racial groups, but the
      aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in
      African American cases, whereas only 19% of the PhIP-DNA adduct variation in
      whites. We conclude that red wine consumption may counteract biological effects
      of PhIP exposure in human prostate, but genetic factors may play an even larger
      role, particularly in African Americans.

PMID- 21846796
TI  - Methyl selenocysteine: single-dose pharmacokinetics in men.
AB  - The recently published report of the SELECT evaluation of selenium and vitamin E
      provided strong evidence that selenium 200 MUg per day in the form of
      selenomethionine does not protect selenium-replete men against prostate or any
      other cancer. This seems to refute the result of the much smaller Nutritional
      Prevention of Cancer (NPC) trial of selenium. Because SELECT did not test the NPC
      agent, it is possible that the difference between the two trials stems partly
      from the use of different agents: selenomethionine in SELECT, and selenized yeast
      in the NPC trial. One of the organic selenium forms suspected of having strong
      chemopreventive effects, and which may have been present in the NPC agent, is
      methyl selenocysteine. This study characterizes the single-dose pharmacokinetics
      of methyl selenocysteine.

PMID- 21846797
TI  - Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting
      aromatase.
AB  - Estradiol is a steroid hormone that not only plays an important role in ovarian
      follicular development but also is associated with many reproductive disorders.
      Owing to the importance of aromatase in the production of estradiol, the
      regulation of aromatase gene expression at the transcriptional level has been an
      extensive area of study for over two decades. However, its regulation at the
      posttranscriptional level has remained unclear. Here, we show that micro-RNA378
      (miR-378) is spatiotemporally expressed in porcine granulosa cells, the cells
      that generate estradiol in the ovary during follicular development, in an inverse
      manner compared with the expression of aromatase. In vitro overexpression and
      inhibition experiments revealed that aromatase expression, and therefore
      estradiol production, by granulosa cells, is posttranscriptionally down-regulated
      by miR-378. Furthermore, site-directed mutation studies identified two binding
      sites in the 3'-untranslated region (3'-UTR) of the aromatase coding sequence
      that are critical for the action of miR-378. Interestingly, overexpression of the
      aromatase 3'-UTR enhanced aromatase expression at the protein level in granulosa
      cells, possibly mediated by the binding of miR-378 within this region, thereby
      reducing the binding of this micro-RNA to the endogenous aromatase 3'-UTR.

PMID- 21846798
TI  - Exposure to chronic pregnancy stress reverses peripartum-associated adaptations:
      implications for postpartum anxiety and mood disorders.
AB  - Maternal adaptations, such as decreased anxiety and attenuated stress
      responsiveness, are necessary to enable successful postnatal development of the
      offspring. However, there is growing evidence that they are also required to
      protect the mental health of the mother and that exposure to chronic stress
      during pregnancy may prevent such adaptations. Overcrowding stress (24 h) and
      restraint stress (2 * 1 h) were employed on alternate days between pregnancy d 4
      16 to examine the impact of chronic pregnancy stress on relevant behavioral,
      neuroendocrine, and neuronal peripartum adaptations. To determine whether the
      chronic stress-induced alterations were specific to the peripartum period, we
      included virgins as controls. Validating the stress procedure, we demonstrated
      decreased body-weight gain and increased adrenal weight in stressed dams,
      relative to their nonstressed controls. Chronic stress prevented a number of
      peripartum adaptations, including basal plasma hypercorticosterone levels,
      increased oxytocin mRNA expression in the hypothalamic paraventricular nucleus,
      and anxiolysis. However, chronic stress did not prevent the peripartum-associated
      decrease in CRH mRNA expression or attenuate corticosterone response to an acute
      stressor, nor did it affect hypothalamic vasopressin mRNA expression.
      Illustrating the specificity of these stress-induced changes to the peripartum
      period, none of these parameters were affected in stressed virgins. Although
      chronic stress did not alter depression-related behavior, it reversed the
      response to acute imipramine treatment and increased active maternal behavior in
      lactation. Thus, prevention of the peripartum-associated increases in basal
      corticosterone and oxytocin system activity by pregnancy stress reveal two
      alterations that may increase the risk of postpartum psychiatric disorders,
      particularly anxiety.

PMID- 21846800
TI  - Melatonin controls photoperiodic changes in tanycyte vimentin and neural cell
      adhesion molecule expression in the Djungarian hamster (Phodopus sungorus).
AB  - The Djungarian hamster displays photoperiodic variations in gonadal size
      synchronized to the seasons by the nightly secretion of the pineal hormone
      melatonin. In short photoperiod (SP), the gonads regress in size, and circulating
      sex steroids levels decline. Thus, the brain is subject to seasonal variations of
      both melatonin and sex steroids. Tanycytes are specialized glial cells located in
      the ependymal lining of the third ventricle. They send processes either to the
      meninges or to blood vessels of the medio-basal hypothalamus. Furthermore, they
      are known to locally modulate GnRH release in the median eminence and to display
      seasonal structural changes. Seasonal changes in tanycyte morphology might be
      mediated either through melatonin or sex steroids. Therefore, we analyzed the
      effects of photoperiod, melatonin, and sex steroids 1) on tanycyte vimentin
      expression by immunohistochemistry and 2) on the expression of the neural cell
      adhesion molecule (NCAM) and polysialic acid as markers of brain plasticity.
      Vimentin immunostaining was reduced in tanycyte cell bodies and processes in SP.
      Similarly, tanycytes and their processes contained lower amounts of NCAM in SP.
      These changes induced by SP exposure could not be restored to long photoperiod
      (LP) levels by testosterone supplementation. Likewise, castration in LP did not
      affect tanycyte vimentin or NCAM expression. By contrast, late afternoon
      melatonin injections mimicking a SP-like melatonin peak in LP hamsters reduced
      vimentin and NCAM expression. Thus, the seasonal changes in vimentin and NCAM
      expression in tanycytes are regulated by melatonin independently of seasonal sex
      steroid changes.

PMID- 21846799
TI  - GH, but not GHRH, plays a role in the development of experimental autoimmune
      encephalomyelitis.
AB  - GH has been suggested to influence the function of the immune system in several
      species. Experimental autoimmune encephalomyelitis (EAE) (an animal model for
      multiple sclerosis) has been reported not to occur in GH-deficient (GHD) mice.
      The aim of this study was to elucidate the effects of GH and GHRH replacement on
      development of EAE in a mouse model of isolated GHD due to removal of the GHRH
      gene [GHRH knockout (GHRHKO)]. We studied two groups of adult female mice: 12 GH
      sufficient animals (control) and 36 GHRHKO animals. All mice were immunized with
      myelin oligodendrocyte glycoprotein peptide, a peptide known to induce EAE.
      GHRHKO mice were left untreated or were treated for 4 wk with daily sc injections
      of recombinant GH or of a GHRH super agonist JI-38 (JI38-GHD). Evaluation of EAE
      symptoms was carried out daily, and T-proliferative assay and histopathological
      analysis of the spinal cord were performed. GHRHKO mice were less prone to
      develop EAE when compared with control mice. GH (but not JI-38) restored the
      original susceptibility of mice to the disease, despite lack of complete serum
      IGF-I normalization. GH treatment was also associated with a markedly increase in
      spleen size and T-cell proliferation specific to myelin oligodendrocyte
      glycoprotein peptide. GH (but not GHRH) plays an important role in the
      development of EAE.

PMID- 21846801
TI  - The hinge region of the TSH receptor stabilizes ligand binding and determines
      different signaling profiles of human and bovine TSH.
AB  - The hinge region (HinR) is a variable structure of glycoprotein hormone
      receptors. Its amino acid composition and length is different for glycoprotein
      hormone receptors and connects the ligand binding domain with the serpentine
      domain. The role of the HinR of the receptors for TSH, follitropin (FSH), and
      LH/choriogonadotropin (LHCG) in receptor and signaling specificity is unknown. To
      investigate the role of the HinR for ligand binding, signal generation, and for
      the transmission of the signal towards the serpentine domain, we replaced the
      HinR of the TSH receptor (TSHR) by those of LHCG receptor and FSH receptor and
      introduced constitutively activating mutations and one mutation deficient for
      bovine (b)TSH binding in these chimeras. Functional characterization of the TSHR
      variants was carried out after transient transfection of COS-7 cells by
      determination of the cell surface expression, ligand binding, and recombinant
      human (rh)TSH or bTSH activation of second messengers. We show that the HinR of
      the TSHR stabilizes hormone binding regarding ligand affinity and retention time
      of the bound ligand as determined by dissociation experiments. Introduction of a
      constitutively activating extracellular loop mutation in these constructs lead to
      partially restored binding patterns. These findings indicate that the HinR
      extracellular loop interface is besides signaling also important for bTSH
      binding. Furthermore, data for G protein signaling reveal that the activity of
      bTSH, but not of rhTSH, depends on the TSHR HinR, which was indicated by a
      significant right shift in the dose-response curves for G(s) and G(q) activation
      for TSHR chimeras harboring the LHCG receptor and FSH receptor HinR,
      respectively. Moreover, we identified different G protein signaling profiles for
      bTSH and rhTSH, which cannot be explained by the characterized HinR. For future
      studies regarding structure and function of the TSHR, it will be necessary to
      characterize TSHR variants with both or more ligands.

PMID- 21846802
TI  - NF-kappaB-inducing kinase (NIK) mediates skeletal muscle insulin resistance:
      blockade by adiponectin.
AB  - Enhanced levels of nuclear factor (NF)-kappaB-inducing kinase (NIK), an upstream
      kinase in the NF-kappaB pathway, have been implicated in the pathogenesis of
      chronic inflammation in diabetes. We investigated whether increased levels of NIK
      could induce skeletal muscle insulin resistance. Six obese subjects with
      metabolic syndrome underwent skeletal muscle biopsies before and six months after
      gastric bypass surgery to quantitate NIK protein levels. L6 skeletal myotubes,
      transfected with NIK wild-type or NIK kinase-dead dominant negative plasmids,
      were treated with insulin alone or with adiponectin and insulin. Effects of NIK
      overexpression on insulin-stimulated glucose uptake were estimated using
      tritiated 2-deoxyglucose uptake. NF-kappaB activation (EMSA),
      phosphatidylinositol 3 (PI3) kinase activity, and phosphorylation of inhibitor
      kappaB kinase beta and serine-threonine kinase (Akt) were measured. After weight
      loss, skeletal muscle NIK protein was significantly reduced in association with
      increased plasma adiponectin and enhanced AMP kinase phosphorylation and insulin
      sensitivity in obese subjects. Enhanced NIK expression in cultured L6 myotubes
      induced a dose-dependent decrease in insulin-stimulated glucose uptake. The
      decrease in insulin-stimulated glucose uptake was associated with a significant
      decrease in PI3 kinase activity and protein kinase B/Akt phosphorylation.
      Overexpression of NIK kinase-dead dominant negative did not affect insulin
      stimulated glucose uptake. Adiponectin treatment inhibited NIK-induced NF-kappaB
      activation and restored insulin sensitivity by restoring PI3 kinase activation
      and subsequent Akt phosphorylation. These results indicate that NIK induces
      insulin resistance and further indicate that adiponectin exerts its insulin
      sensitizing effect by suppressing NIK-induced skeletal muscle inflammation. These
      observations suggest that NIK could be an important therapeutic target for the
      treatment of insulin resistance associated with inflammation in obesity and type
      2 diabetes.

PMID- 21846803
TI  - Specific regulatory motifs predict glucocorticoid responsiveness of hippocampal
      gene expression.
AB  - The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated
      transcription factor that mediates effects of cortisol in relation to adaptation
      to stress. In the brain, GR affects the hippocampus to modulate memory processes
      through direct binding to glucocorticoid response elements (GREs) in the DNA.
      However, its effects are to a high degree cell specific, and its target genes in
      different cell types as well as the mechanisms conferring this specificity are
      largely unknown. To gain insight in hippocampal GR signaling, we characterized to
      which GRE GR binds in the rat hippocampus. Using a position-specific scoring
      matrix, we identified evolutionary-conserved putative GREs from a microarray
      based set of hippocampal target genes. Using chromatin immunoprecipitation, we
      were able to confirm GR binding to 15 out of a selection of 32 predicted sites
      (47%). The majority of these 15 GREs are previously undescribed and thus
      represent novel GREs that bind GR and therefore may be functional in the rat
      hippocampus. GRE nucleotide composition was not predictive for binding of GR to a
      GRE. A search for conserved flanking sequences that may predict GR-GRE
      interaction resulted in the identification of GC-box associated motifs, such as
      Myc-associated zinc finger protein 1, within 2 kb of GREs with GR binding in the
      hippocampus. This enrichment was not present around nonbinding GRE sequences nor
      around proven GR-binding sites from a mesenchymal stem-like cell dataset that we
      analyzed. GC-binding transcription factors therefore may be unique partners for
      DNA-bound GR and may in part explain cell-specific transcriptional regulation by
      glucocorticoids in the context of the hippocampus.

PMID- 21846805
TI  - Differential effects of exogenous androgen and an androgen receptor antagonist in
      the peri- and postpubertal murine mammary gland.
AB  - There is emerging evidence that androgens inhibit proliferation of normal and
      malignant breast epithelial cells, but the actions of androgens in normal mammary
      gland morphogenesis are not well understood. In this study, we investigated
      whether development of the murine mammary gland could be altered by stimulating
      or suppressing androgen receptor (AR) signaling in vivo. Intact virgin female
      mice aged 5 wk (midpuberty) or 12 wk (postpuberty) were implanted with slow
      release pellets containing either placebo, 5alpha-dihydrotestosterone (1.5 mg) or
      the AR antagonist flutamide (60 mg). Treatment with 5alpha-dihydrotestosterone
      from midpuberty to 12 wk of age-retarded ductal extension by 40% (P = 0.007), but
      treatment from 12-21 wk had no significant effect on gland morphology. In
      contrast, inhibition of AR signaling with flutamide from midpuberty had no effect
      on the mammary gland, but flutamide treatment from 12-21 wk increased ductal
      branching (P = 0.004) and proliferation (P = 0.03) of breast epithelial cells.
      The increased proliferation in flutamide-treated mice was not correlated with
      serum estradiol levels or estrogen receptor-alpha (ERalpha) expression. In
      control mice, the frequency and intensity of AR immunostaining in mammary
      epithelial cells was significantly increased in the 12- to 21-wk treatment group
      compared with the 5- to 12-wk group (P < 0.001). In contrast, no change in
      ERalpha occurred, resulting in a marked increase in the AR to ERalpha ratio from
      0.56 (+/-0.12) to 1.47 (+/-0.10). Our findings indicate that androgen signaling
      influences development and structure of the adult mammary gland and that
      homeostasis between estrogen and androgen signaling in mature glands is critical
      to constrain the proliferative effects of estradiol.

PMID- 21846804
TI  - Inhibition of renin release by arachidonic acid metabolites, 12(s)-HPETE and 12
      HETE: role of TRPV1 channels.
AB  - We test the hypothesis that 12-hydroperoxyeicosatetraenoic acid (12(s)-HPETE) and
      12-hydroxyeicosatetraenoic acid (12-HETE) perfused into the renal pelvis increase
      afferent renal nerve activity (ARNA) and suppress renin release in rats fed a low
      salt (LS) diet via activation of the transient receptor potential vanilloid type
      1 (TRPV1) expressed in renal sensory nerves. 12(s)-HPETE or 12-HETE given into
      the left renal pelvis dose-dependently increased ARNA, which was abolished by
      AMG9810, a selective TRPV1 antagonist, or by RP67580, a selective neurokinin 1
      receptor antagonist, in normal salt or LS-treated rats. 12(s)-HPETE, 12-HETE, or
      substance P perfused into the left renal pelvis suppressed plasma angiotensin I
      (Ang I) levels in LS rats, which was abolished by AMG9810 or attenuated by
      ipsilateral renal denervation (RD). 12(s)-HPETE or 12-HETE increased release of
      substance P and calcitonin gene-related peptide from the ipsilateral kidney,
      which was abolished by AMG9810 but not RP67580, RD, or RP67580 plus RD.
      Immunofluorescence staining showed that TRPV1-positive nerve fibers located in
      the renal cortex, medulla, and pelvis, and that the sympathetic nerve marker,
      neuropeptide Y, but not neurokinin 1 receptors expressed in the juxtaglomerular
      region colocalized with renin. Thus, our data show that 12(s)-HPETE and 12-HETE
      enhance ARNA and substance P/calcitonin gene-related peptide release but suppress
      renin activity in LS rats, and these effects are abolished when TRPV1 is blocked.
      These results indicate that TRPV1 mediates 12(s)-HPETE and 12-HETE action in the
      kidney in such a way that dysfunction in TRPV1 may lead to disintegrated
      regulation of renin and renal function.

PMID- 21846807
TI  - Immortalized mouse embryo fibroblasts are resistant to miR-290-induced senescence
      regardless of p53 status.
AB  - The prosenescence role of miR-290 and nocodazole has been documented in primary
      mouse embryo fibroblasts (MEF), while it is not clear whether immortal murine
      fibroblasts are still responsive to these senescence inducing stimuli. To
      establish this point, immortal murine fibroblasts with functional (NIH3T3) or
      nonfunctional p53 (I-MEF) and low levels of miR-290 were tested for their
      capability to undergo senescence after exposure to either nocodazole or miR-290.
      Our results clearly indicate that nocodazole induces senescence only in NIH3T3
      cells with a functional p53 but not in I-MEF lacking a functional p53. miR-290
      overexpression is unable to address any of the tested immortalized clones toward
      senescence, regardless of the p53 status, suggesting that the prosenescence role
      of miR-290 is specific for primary but not for immortal murine fibroblasts.
      Moreover our findings suggest that the mere downregulation of a potential tumor
      suppressor miRNA in a given cell type does not necessarily imply that it behaves
      as a tumor suppressor.

PMID- 21846806
TI  - Integrated genomic approaches to identification of candidate genes underlying
      metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat.
AB  - The spontaneously hypertensive rat (SHR) is a widely used rodent model of
      hypertension and metabolic syndrome. Previously we identified thousands of cis
      regulated expression quantitative trait loci (eQTLs) across multiple tissues
      using a panel of rat recombinant inbred (RI) strains derived from Brown Norway
      and SHR progenitors. These cis-eQTLs represent potential susceptibility loci
      underlying physiological and pathophysiological traits manifested in SHR. We have
      prioritized 60 cis-eQTLs and confirmed differential expression between the
      parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts.
      Quantitative trait transcript (QTT) analysis in the RI strains showed highly
      significant correlation between cis-eQTL transcript abundance and clinically
      relevant traits such as systolic blood pressure and blood glucose, with the
      physical location of a subset of the cis-eQTLs colocalizing with "physiological"
      QTLs (pQTLs) for these same traits. These colocalizing correlated cis-eQTLs (c3
      eQTLs) are highly attractive as primary susceptibility loci for the colocalizing
      pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single
      nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor
      binding affinity, splicing and protein function. These SNPs, which potentially
      alter transcript abundance and stability, represent strong candidate factors
      underlying not just eQTL expression phenotypes, but also the correlated metabolic
      and physiological traits. In conclusion, by integration of genomic sequence, eQTL
      and QTT datasets we have identified several genes that are strong positional
      candidates for pathophysiological traits observed in the SHR strain. These
      findings provide a basis for the functional testing and ultimate elucidation of
      the molecular basis of these metabolic and cardiovascular phenotypes.

PMID- 21846808
TI  - The influence of balance confidence on social activity after discharge from
      prosthetic rehabilitation for first lower limb amputation.
AB  - BACKGROUND: Community living individuals with lower limb amputation have low
      balance confidence but the level of balance confidence in the first six months
      after discharge from prosthetic rehabilitation is not known. OBJECTIVES: To
      determine if balance confidence levels differ after discharge from prosthetic
      rehabilitation and to determine if balance confidence at discharge predicts
      social activity at three months post-discharge while controlling for important
      covariates such as walking ability. STUDY DESIGN: Prospective study. METHODS:
      Subjects (n = 65) experiencing their first unilateral transfemoral or transtibial
      amputation were recruited and followed-up one and three months post-discharge.
      Measures of balance confidence (Activities-specific Balance Confidence Scale) and
      walking ability (L Test) collected at discharge were used to predict social
      activity (Frenchay Activities Index) at follow-up. RESULTS: Despite a 14-second
      mean improvement in walking ability the mean balance confidence scores did not
      change significantly between discharge (71.2/100) and at three-month follow-up
      (69.4/100). Confidence scores and basic walking ability at discharge were the two
      strongest predictors of three-month social activity. Multiple regression
      modelling indicated that balance confidence and walking ability explained 64% of
      the variance (standardized beta = 0.34 and -0.37 respectively) in social activity
      (adjusted R(2) = 39%). CONCLUSIONS: Balance confidence after discharge from
      prosthetic rehabilitation for lower limb amputation is low and scores do not
      improve over the first three months post-discharge despite improvements in
      walking ability. Discharge balance scores confidence independently predicts three
      month social activity scores.

PMID- 21846809
TI  - Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA
      binding protein targets during mouse preimplantation development.
AB  - During oogenesis, mammalian oocytes accumulate maternal mRNAs that support the
      embryo until embryonic genome activation. RNA-binding proteins (RBP) may regulate
      the stability and turnover of maternal and embryonic mRNAs. We hypothesised that
      varying embryo culture conditions, such as culture medium, oxygen tension and
      MAPK inhibition, affects regulation of RBPs and their targets during
      preimplantation development. STAU1, ELAVL1, KHSRP and ZFP36 proteins and mRNAs
      were detected throughout mouse preimplantation development, whereas Elavl2 mRNA
      decreased after the two-cell stage. Potential target mRNAs of RBP regulation,
      Gclc, Slc2a1 and Slc7a1 were detected during mouse preimplantation development.
      Gclc mRNA was significantly elevated in embryos cultured in Whitten's medium
      compared with embryos cultured in KSOMaa, and Gclc mRNA was elevated under high
      oxygen conditions. Inhibition of the p38 MAPK pathway reduced Slc7a1 mRNA
      expression while inhibition of ERK increased Slc2a1 mRNA expression. The half
      lives of the potential RBP mRNA targets are not regulated in parallel; Slc2a1
      mRNA displayed the longest half-life. Our results indicate that mRNAs and
      proteins encoding five RBPs are present during preimplantation development and
      more importantly, demonstrate that expression of RBP target mRNAs are regulated
      by culture medium, gas atmosphere and MAPK pathways.

PMID- 21846810
TI  - Production of live foals via intracytoplasmic injection of lyophilized sperm and
      sperm extract in the horse.
AB  - Work with lyophilized sperm helps delineate the factors required for successful
      fertilization. We investigated the use of lyophilized sperm in equine embryo
      production. In Experiment 1, sperm DNA fragmentation index was not affected by
      three freeze/thaw or lyophilization cycles. In Experiment 2, oocytes injected
      with lyophilized sperm or with sperm from a treatment in which lyophilized sperm
      were suspended in sperm cytoplasmic extract (SE) yielded blastocyst development
      rates of 0 and 28% respectively (P < 0.05). In Experiment 3, blastocyst
      development rate was 6-11% after injection of sperm lyophilized from fresh or
      frozen-thawed semen, suspended in SE. In Experiment 4, sperm lyophilized 3.5
      months or 1 week previously, suspended in SE, yielded similar blastocyst rates (6
      and 3% respectively). Rates of normal pregnancy after transfer were 7/10 and 5/7
      for embryos from control and lyophilized sperm treatments respectively. Three
      pregnancies from the lyophilized sperm treatments were not terminated, resulting
      in two healthy foals. Parentage testing determined that one foal originated from
      the lyophilized sperm; the other was the offspring of the stallion providing the
      sperm extract. Further testing indicated that two of five additional embryos in
      the lyophilized sperm treatment originated from the stallion providing the sperm
      extract. We conclude that both lyophilized stallion sperm and stallion sperm
      processed by multiple unprotected freeze-thaw cycles (as for sperm extract) can
      support production of viable foals. To the best of our knowledge, this is the
      first report on production of live offspring by fertilization with lyophilized
      sperm in a non-laboratory animal species.

PMID- 21846811
TI  - Violence and psychological distress among police officers and security guards.
AB  - BACKGROUND: Police officers and security guards are more exposed to violence
      during their work duties than the general workforce and it can damage their
      psychological health. Still research on specific forms of violence and a
      potential pathway through which violence may affect distress is scarce. AIMS: The
      aim of this study was to investigate the association of two forms of violence
      with distress among police officers and security guards and whether personal
      worry about future violence mediates this association. METHODS: Violence was
      specified as physically violent acts and threats or assaults with a deadly
      weapon. Symptoms of psychological distress were measured using the General Health
      Questionnaire-12 scale. RESULTS: Analyses of 1993 completed responses (response
      rate 58%) showed that the odds ratio of distress for 'physically violent acts
      was' 1.67 (95% CI = 1.11-2.51) and for 'threats or assaults with a deadly weapon'
      1.62 (95% CI = 1.20-2.17). When personal worry about future violence was taken
      into account, the association between exposure to physically violent acts and
      distress was completely broken. Instead, with the same adjustment, the
      association between exposure to threats or assaults with a deadly weapon and
      distress held. The results indicate that the association between physically
      violent acts and distress is mediated by personal worry about future violence,
      while threats or assaults with a deadly weapon had a stronger and independent
      association with distress. CONCLUSIONS: It is concluded that there is association
      between violence and distress. Personal worry about future violence mediates this
      association.

PMID- 21846812
TI  - Development and validation of a screening questionnaire for noise-induced hearing
      loss.
AB  - BACKGROUND: An audiometric health surveillance programme can be perceived to be a
      relatively costly exercise and employers, especially in developing countries,
      might therefore be reluctant to undertake this. A questionnaire might be a
      cheaper alternative. AIMS: To develop a questionnaire to help determine the
      prevalence of noise-induced hearing loss (NIHL) in the vernacular (language) of a
      developing country and to validate it against an audiometric standard. METHODS: A
      questionnaire was developed, translated and administered in a face-to-face
      interview. Otoscopic examination was followed by conventional pure-tone
      audiometry (at 0.25, 0.5, 1, 2, 4 and 8 kHz) for both ears of each respondent.
      The questionnaire responses were compared to the audiometric standard. RESULTS:
      Two hundred and fifty workers from three companies (two printing and one
      woodworking) participated in this study. The sensitivity of the hearing loss
      questionnaire in detecting noise-induced hearing loss was 32%, while its
      specificity was 79%. There was an evidence to suggest good agreement (r = 0.523)
      between the total number of years worked in noisy jobs and NIHL (P < 0.05).
      CONCLUSIONS: The questionnaire developed in this study was found to have an
      unacceptably low sensitivity for noise-induced hearing loss and therefore cannot
      be a valid substitute for audiometry. Pure tone industrial audiometry needs to be
      used more widely than currently in developing countries.

PMID- 21846813
TI  - Multi-site pain and work ability among an industrial population.
AB  - BACKGROUND: Multi-site pain is a common phenomenon among working-age people and
      it strongly increases work disability risk. Little is known about the impact of
      musculoskeletal pain on work ability. AIMS: To investigate whether the number of
      musculoskeletal pain sites predicts future poor work ability. METHODS: The study
      was conducted in 2005 and 2009 in a food processing company. A total of 734
      workers participated in the study. The information on self-perceived work ability
      and musculoskeletal pain during the preceding week was obtained through a
      structured questionnaire distributed to employees. The risk of poor work ability
      at follow-up related to the number of pain sites at baseline was estimated with
      logistic regression. RESULTS: The proportion of poor work ability increased in 4
      years from 15 to 22%, parallel to the increase in the number of pain sites. Among
      those with 'non-poor' work ability at baseline, one-tenth reported their work
      ability to be poor after 4 years. The number of pain sites predicted poor work
      ability after 4 years of follow-up with a dose-response manner. Those with
      widespread pain had almost a 3-fold risk of developing poor work ability at
      follow-up. The associations were stronger for younger and white-collar workers.
      CONCLUSIONS: The results of the present study indicate that multi-site
      musculoskeletal pain at baseline strongly predicts poor work ability after 4
      years among industrial workers. Counting the number of concurrent pain sites may
      be a simple method of identifying workers with high risk of work disability in
      occupational health practice.

PMID- 21846814
TI  - An autoimmunized mouse model recapitulates key features in the pathogenesis of
      Sjogren's syndrome.
AB  - The pathogenesis of Sjogren's syndrome (SS) is poorly understood. To evaluate an
      autoimmunization-induced experimental SS model, we firstly observed the phenotype
      of lymphocyte infiltration in the enlarged submandibular gland (SG). Furthermore,
      significant activation of caspase-3 and a high ratio of Bax-to-Bcl-2 were
      detected, indicating the inflammatory apoptosis associated with developmental
      foci. Meanwhile, the dysregulated cytokines, such as tumor necrosis factor alpha,
      IL-1beta and IL-6 mRNA expression, were found to be over-expressed. A progressive
      decrease of aquaporin 5 and its subcellular translocation from apical to basal
      membrane in SG was found to be associated with the abnormally expressed M3
      muscarinic acetylcholine receptor. This pattern was found to be similar to that
      seen in human SS and possibly contributed to the saliva secretion deficiency.
      Thus, this autoimmunization-induced model recapitulates the key features of human
      SS and may have potential for studying the pathogenesis of human SS.

PMID- 21846815
TI  - Metabolomics of a single vacuole reveals metabolic dynamism in an alga Chara
      australis.
AB  - Metabolomics is the most reliable analytical method for understanding metabolic
      diversity in single organelles derived from single cells. Although metabolites
      such as phosphate compounds are believed to be localized in different organelles
      in a highly specific manner, the process of metabolite compartmentalization in
      the cell is not thoroughly understood. The analysis of metabolites in single
      organelles has consequently presented a significant challenge. In this study, we
      used a metabolomic method to elucidate the localization and dynamics of 125 known
      metabolites isolated from the vacuole and cytoplasm of a single cell of the alga
      Chara australis. The amount of metabolites in the vacuole and the cytoplasm
      fluctuated asynchronously under various stress conditions, suggesting that
      metabolites are spatially regulated within the cell. Metabolite transport across
      the vacuolar membrane can be directly detected using the microinjection
      technique, which may reveal a previously unknown function of the vacuole.

PMID- 21846817
TI  - Getting on with life: positive experiences of living with a spinal cord injury.
AB  - Currently, the dominant cultural beliefs toward disability are negative, and the
      existing literature is limited with respect to examining how people are using
      and/or viewing their disabilities positively. The purpose of this study was to
      identify how individuals living with a spinal cord injury (SCI) viewed and/or
      used their disability positively, and what contextual influences facilitated this
      positive approach. This study was a secondary analysis of qualitative data from a
      larger study. The findings revealed three levels at which disability was viewed
      and/or used positively by people with SCI: self, peers, and disability community.
      In addition, several aspects of the participants' situations were found to
      facilitate this positive view and/or use of disability: personality,
      spirituality, support systems, and acceptance of one's disability. The findings
      reveal that individuals with SCI are viewing and/or using their disabilities
      positively in many different ways. This study has significant implications for
      the direction of future research and for health care professionals who need to
      increase their advocacy and facilitating roles.

PMID- 21846818
TI  - Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic
      markers of prostate cancer-specific mortality.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer-related deaths
      in men, accounting for more than 30,000 deaths annually. The purpose of this
      study was to test whether variation in selected candidate genes in biological
      pathways of interest for prostate cancer progression could help distinguish
      patients at higher risk for fatal prostate cancer. METHODS: In this hypothesis
      driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156
      candidate genes in a population-based cohort of 1,309 prostate cancer patients.
      We identified 22 top-ranking SNPs (P <= 0.01, FDR <= 0.70) associated with
      prostate cancer-specific mortality (PCSM). A subsequent validation study was
      completed in an independent population-based cohort of 2,875 prostate cancer
      patients. RESULTS: Five SNPs were validated (P <= 0.05) as being significantly
      associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes.
      Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at
      risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased
      with the number of at-risk genotypes carried (P(trend) = 0.001), adjusting for
      clinicopathologic factors known to influence prognosis. CONCLUSION: Five genetic
      markers were validated to be associated with lethal prostate cancer. IMPACT: This
      is the first population-based study to show that germline genetic variants
      provide prognostic information for prostate cancer-specific survival. The
      clinical utility of this five-SNP panel to stratify patients at higher risk for
      adverse outcomes should be evaluated.

PMID- 21846819
TI  - Autoantibodies to mesothelin in infertility.
AB  - BACKGROUND: According to extensive epidemiologic data, infertility is associated
      with increased ovarian cancer risk. Previous studies showed that both women with
      infertility and those with ovarian cancer have autoantibodies to ovarian
      antigens. The objective was to determine if women with infertility have
      antibodies to mesothelin, a well-characterized ovarian cancer antigen. METHODS:
      Sera were obtained from women with infertility (n = 109), ovarian cancer (n =
      28), benign ovarian tumors or cysts (n = 24), and from healthy women (n = 152).
      Infertility included those with a risk for ovarian cancer; endometriosis (n =
      23), ovulatory dysfunction (n = 17), premature ovarian failure (POF; n = 25) and
      unexplained infertility (n = 44). Sera were assayed for mesothelin antibodies and
      for circulating mesothelin antigen by immunoassay and compared with assay control
      sera (n = 16) to determine a positive result. RESULTS: Mesothelin antibodies were
      significantly more frequent in women with prematurely reduced ovarian function
      including ovulatory dysfunction (59%), ovarian failure (44%) and unexplained
      infertility (25%) compared with controls. In contrast, women with endometriosis,
      who also have a high risk for ovarian cancer, did not have mesothelin antibodies.
      Serum levels of mesothelin were rarely elevated in women with infertility but
      were high in most patients with ovarian cancer. CONCLUSIONS AND IMPACT: We show
      for the first time that antibodies to mesothelin, a well-characterized ovarian
      cancer antigen, occur in some women with epidemiologic risk for ovarian cancer.
      The results suggest it may be possible to identify which women with infertility
      have ovarian cancer risk.

PMID- 21846820
TI  - Parity and lactation in relation to estrogen receptor negative breast cancer in
      African American women.
AB  - BACKGROUND: Estrogen receptor (ER)-negative breast tumors and progesterone
      receptor (PR)-negative breast tumors occur more commonly in women of African
      ancestry. Recent research indicates that the effects of reproductive factors may
      differ by hormone receptor status. We assessed the relation of parity and
      lactation to incidence of ER(-)/PR(-) and ER(+)/PR(+) breast cancer in a cohort
      of African American women. METHODS: From 1995-2009, 457 incident cases of
      ER(+)/PR(+) and 318 cases of ER(-)/PR(-) breast cancer were confirmed by review
      of pathology data among 59,000 African American women followed in the Black
      Women's Health Study through biennial questionnaires. HRs and two-sided 95% CIs
      for the incidence of breast cancer subtypes were derived from proportional
      hazards regression models that controlled for age, reproductive variables, and
      breast cancer risk factors. RESULTS: Higher parity was associated with an
      increased risk of ER(-)/PR(-) breast cancer (HR = 1.48, 95% CI: 0.98-1.84 for 3+
      versus 0 births, P(trend) = 0.009), and with a reduced risk of ER(+)/PR(+) cancer
      (HR = 0.53, 95% CI: 0.39-0.73 for 3+ versus 0 births, P(trend) = 0.0002). Among
      women who had breastfed, high parity was no longer associated with increased
      incidence of ER(-)/PR(-) breast, but the inverse association with ER(+)/PR(+)
      cancer persisted. CONCLUSIONS: The higher incidence of ER(-)/PR(-) breast cancer
      in African American women may be explained in part by their higher parity and
      lower prevalence of breastfeeding relative to white women. IMPACT: Increased
      breastfeeding may lead to a reduction in the incidence of this breast cancer
      subtype.

PMID- 21846821
TI  - Development of a hypoxia gene expression classifier with predictive impact for
      hypoxic modification of radiotherapy in head and neck cancer.
AB  - Hypoxia, a common feature of the microenvironment in solid tumors, is associated
      with resistance to radiotherapy, reduced therapeutic response, and a poorer
      clinical outcome. In head and neck squamous cell carcinomas (HNSCC), the negative
      effect of hypoxia on radiotherapy can be counteracted via addition of hypoxic
      modification to the radiotherapy. To predict which patients harbor hypoxic tumors
      and would therefore benefit from hypoxic modification, clinically applicable
      methods for pretherapeutic hypoxic evaluation and categorization are needed. In
      this study, we developed a hypoxia classifier based on gene expression. Through
      study of xenograft tumors from human squamous cell carcinoma cell lines, we
      verified the in vivo relevance of previously identified in vitro derived hypoxia
      induced genes. We then evaluated a training set of 58 hypoxia-evaluated HNSCCs to
      generate a gene expression classifier containing 15 genes. This 15-gene hypoxia
      classifier was validated in 323 patients with HNSCC randomized for hypoxic
      modification or placebo in combination with radiotherapy. Tumors categorized as
      hypoxic on the basis of the classifier were associated with a significantly
      poorer clinical outcome than nonhypoxic tumors. This outcome was improved and
      equalized to the nonhypoxic tumors by addition of hypoxic modification. Thus,
      findings show that the classifier attained both prognostic and predictive impact,
      and its pretherapeutic use may provide a method to identify those patients who
      will benefit from hypoxic modification of radiotherapy.

PMID- 21846822
TI  - Prognostic and predictive impact of intra- and peritumoral immune infiltrates.
AB  - Leukocyte infiltrates into or around tumor cell nests are found in the context of
      protumorigenic inflammation and anticancer immunosurveillance. Hence, the
      detailed composition, density, architecture, and function of leukocyte
      infiltrates must be analyzed to understand their prognostic impact. The ectopic
      presence within tumors of high endothelial venule cells, which are normally
      characteristic for secondary lymphoid organs, correlates with a more pronounced
      infiltration by T lymphocytes and has a positive predictive impact on local
      advanced breast cancer treated with neoadjuvant chemotherapy. Recent progress in
      the field indicates that immune infiltrates of the primary tumors, as well as of
      metastases, are not only independent prognostic biomarkers but can also
      constitute predictive factors, suggesting that the pretherapeutic immune response
      can determine the efficacy of conventional chemotherapies. Moreover, accumulating
      evidence indicates that chemotherapy can stimulate anticancer immune responses
      coupled with an increased intratumoral lymphoid infiltration, which correlates
      with tumor mass reduction and patient survival. Improved methods for the
      automation of immunohistochemistry and digitalized image analyses will pave the
      way to an improved understanding of the complex interplay between cancer
      parenchyma, stroma, and immune effectors, as well as to the routine evaluation of
      immune-related parameters to the clinical management of cancer patients.

PMID- 21846823
TI  - Human solid tumors contain high endothelial venules: association with T- and B
      lymphocyte infiltration and favorable prognosis in breast cancer.
AB  - The mechanisms governing infiltration of lymphocytes into tumors remain poorly
      characterized, in spite of the critical impact of these cells on patient
      prognosis and therapeutic responses. High endothelial venules (HEV) are blood
      vessels found in lymphoid tissues, specialized in lymphocyte recruitment, but
      their implications in human cancer are unknown. In this article, we report the
      presence of MECA 79(+) blood vessels displaying all the phenotypic
      characteristics of HEVs in most of the 319 human primary solid tumors, including
      melanomas, breast, ovarian, colon, and lung carcinomas, analyzed. Tumor HEVs were
      specifically located within lymphocyte-rich areas, and their density within the
      tumor stroma was a strong predictor of infiltration by CD3(+) and CD8(+) T cells
      as well as B cells. Large-scale flow cytometric and quantitative reverse
      transcriptase-PCR analyses in freshly operated breast tumors revealed that high
      densities of tumor HEVs correlated with increased naive, central memory and
      activated effector memory T-cell infiltration and upregulation of genes related
      to T-helper 1 adaptive immunity and T-cell cytotoxicity. Finally, in a
      retrospective cohort of 146 invasive breast cancer patients, we found that high
      densities of tumor HEVs independently conferred a lower risk of relapse and
      significantly correlated with longer metastasis-free, disease-free, and overall
      survival rates. Together, our findings suggest that tumor HEVs function as major
      gateways for lymphocyte infiltration into human tumors, and may represent
      attractive targets for cancer diagnosis and therapy.

PMID- 21846824
TI  - Localization and density of immune cells in the invasive margin of human
      colorectal cancer liver metastases are prognostic for response to chemotherapy.
AB  - Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal
      cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that
      the adaptive immune response influences the course of human CRC. Specifically,
      high densities of TILs in the primary tumor are associated with good prognosis
      independent of other prognostic markers. However, the prognostic role of TILs in
      metastatic CRC lesions is unknown, as is their role in response or resistance to
      conventional chemotherapy. We analyzed the association of TIL densities at the
      invasive margin of CRC liver metastases with response to chemotherapy and
      progression-free survival in a set of 101 large section samples. High-resolution
      automated microscopy on complete tissue sections was used to objectively generate
      cell densities for CD3, CD8, granzyme B, or FOXP3 positive immune cells. A
      predictive scoring system using TIL densities was developed in a training set and
      tested successfully in an independent validation set. TIL densities at the
      invasive margin of liver metastases allowed the prediction of response to
      chemotherapy with a sensitivity of 79% and specificity of 100%. The association
      of high density values with longer progression-free survival under chemotherapy
      was statistically significant. Overall, these findings extend the impact of the
      local immune response on the clinical course from the primary tumor also to
      metastatic lesions. Because detailed quantification of TILs in metastatic lesions
      revealed a strong association with chemotherapy efficacy and prognosis, we
      suggest that the developed scoring system may be used as a predictive tool for
      response to chemotherapy in metastatic CRC.

PMID- 21846827
TI  - Shifting paradigm on Bacillus thuringiensis toxin and a natural model for
      Enterococcus faecalis septicemia.
AB  - The Bt toxin is widely used in agriculture both as a spray and in transgenic
      plants, yet its precise mode of action against lepidopterans is poorly
      understood. The study by Mason et al. [mBio 2(3):e00065-11, 2011] revealed that
      Bt toxin enables an inhabitant of the midgut, Enterococcus faecalis, to enter the
      hemolymph of larvae and cause septicemia, leading to death.

PMID- 21846828
TI  - Host- and strain-specific regulation of influenza virus polymerase activity by
      interacting cellular proteins.
AB  - Highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype have
      recently emerged from avian zoonotic reservoirs to cause fatal human disease.
      Adaptation of HPAI virus RNA-dependent RNA polymerase (PB1, PB2, and PA proteins)
      and nucleoprotein (NP) to interactions with mammalian host proteins is thought to
      contribute to the efficiency of viral RNA synthesis and to disease severity.
      While proteomics experiments have identified a number of human proteins that
      associate with H1N1 polymerases and/or viral ribonucleoprotein (vRNP), how these
      host interactions might regulate influenza virus polymerase functions and host
      adaptation has been largely unexplored. We took a functional genomics (RNA
      interference [RNAi]) approach to assess the roles of a network of human proteins
      interacting with influenza virus polymerase proteins in viral polymerase activity
      from prototype H1N1 and H5N1 viruses. A majority (18 of 31) of the cellular
      proteins tested, including RNA-binding (DDX17, DDX5, NPM1, and hnRNPM), stress
      (PARP1, DDB1, and Ku70/86), and intracellular transport proteins, were required
      for efficient activity of both H1N1 and H5N1 polymerases. NXP2 and NF90
      antagonized both polymerases, and six more RNA-associated proteins exhibited
      strain-specific phenotypes. Remarkably, 12 proteins differentially regulated H5N1
      polymerase according to PB2 genotype at mammalian-adaptive residue 627. Among
      these, DEAD box RNA helicase DDX17/p72 facilitated efficient human-adapted (627K)
      H5N1 virus mRNA and viral RNA (vRNA) synthesis in human cells. Likewise, the
      chicken DDX17 homologue was required for efficient avian (627E) H5N1 infection in
      chicken DF-1 fibroblasts, suggesting that this conserved virus-host interaction
      contributes to PB2-dependent host species specificity of influenza virus and
      ultimately to the outcome of human HPAI infections. IMPORTANCE: Highly pathogenic
      avian influenza A (HPAI) viruses have recently emerged from wild and domestic
      birds to cause fatal human disease. In human patients, it is thought that
      adaptation of the viral polymerase, a complex of viral proteins responsible for
      viral gene expression and RNA genome replication, to interactions with mammalian
      rather than avian host proteins contributes to disease severity. In this study,
      we used computational analysis and RNA interference (RNAi) experiments to
      identify a biological network of human proteins that regulates an H5N1 HPAI virus
      polymerase, in comparison to a mammalian H1N1 virus. Of 31 proteins tested, 18
      (58%) were required for polymerase function in both HPAI and H1N1 viruses.
      Remarkably, we also found proteins such as DDX17 that governed the HPAI virus
      polymerase's adaptation to human cells. These virus-host interactions may thus
      control pathogenicity of HPAI virus in humans and are promising therapeutic
      targets for antiviral drugs in severe influenza infections.

PMID- 21846829
TI  - Identification of circulating bacterial antigens by in vivo microbial antigen
      discovery.
AB  - Detection of microbial antigens in clinical samples can lead to rapid diagnosis
      of an infection and administration of appropriate therapeutics. A major barrier
      in diagnostics development is determining which of the potentially hundreds or
      thousands of antigens produced by a microbe are actually present in patient
      samples in detectable amounts against a background of innumerable host proteins.
      In this report, we describe a strategy, termed in vivo microbial antigen
      discovery (InMAD), that we used to identify circulating bacterial antigens. This
      technique starts with "InMAD serum," which is filtered serum that has been
      harvested from BALB/c mice infected with a bacterial pathogen. The InMAD serum,
      which is free of whole bacterial cells, is used to immunize syngeneic BALB/c
      mice. The resulting "InMAD immune serum" contains antibodies specific for the
      soluble microbial antigens present in sera from the infected mice. The InMAD
      immune serum is then used to probe blots of bacterial lysates or bacterial
      proteome arrays. Bacterial antigens that are reactive with the InMAD immune serum
      are precisely the antigens to target in an antigen immunoassay. By employing
      InMAD, we identified multiple circulating antigens that are secreted or shed
      during infection using Burkholderia pseudomallei and Francisella tularensis as
      model organisms. Potential diagnostic targets identified by the InMAD approach
      included bacterial proteins, capsular polysaccharide, and lipopolysaccharide. The
      InMAD technique makes no assumptions other than immunogenicity and has the
      potential to be a broad discovery platform to identify diagnostic targets from
      microbial pathogens. IMPORTANCE: Effective treatment of microbial infection is
      critically dependent on early diagnosis and identification of the etiological
      agent. One means for rapid diagnosis is immunoassay for antigens that are shed
      into body fluids during infection. Immunoassays can be inexpensive, rapid, and
      adaptable to a point-of-care format. A major impediment to immunoassay for
      diagnosis of infectious disease is identification of appropriate antigen targets.
      This report describes a strategy that can be used for identification of microbial
      antigens that are shed into serum during infection by the biothreats Burkholderia
      pseudomallei and Francisella tularensis. Termed InMAD (in vivo microbial antigen
      discovery), the strategy has the potential for application to a broad spectrum of
      microbial pathogens.

PMID- 21846831
TI  - Syphilis treatment in the human immunodeficiency virus-infected patient: follow
      the guidelines.

PMID- 21846830
TI  - Novel irreversible small molecule inhibitors of replication protein A display
      single-agent activity and synergize with cisplatin.
AB  - Replication protein A (RPA) is a single-strand DNA-binding protein with essential
      roles in DNA replication, recombination, and repair. It is necessary for the
      formation of the preincision complex that is required for proper incision of
      damaged DNA nucleotides during DNA repair. We have previously identified small
      molecule inhibitors (SMI) with the ability to disrupt RPA-binding activity to
      ssDNA. Further characterization of these RPA inhibitors was done using both lung
      and ovarian cancer cell lines. Lung cancer cell lines showed increased apoptotic
      cell death following treatment with the SMI MCI13E, with IC(50) values of
      approximately 5 MUmol/L. The ovarian cancer cell line A2780 and the p53-null lung
      cancer cell line H1299 were particularly sensitive to MCI13E treatment, with
      IC(50) values less than 3 MUmol/L. Furthermore, a cell-cycle effect was observed
      in lung cancer cell lines that resulted in a lengthening of either G(1) or S
      phases of the cell cycle following single-agent treatment. Sequential treatment
      with MCI13E and cisplatin resulted in synergism. Overall, these data suggest that
      decreasing DNA-binding activity of RPA via a SMI may disrupt the role of RPA in
      cell-cycle regulation. Thus, SMIs of RPA hold the potential to be used as single
      agent chemotherapeutics or in combination with current chemotherapeutic regimens
      to increase efficacy.

PMID- 21846832
TI  - High incidence of chlorhexidine-induced rash among Thai health care workers.

PMID- 21846833
TI  - Dosing voriconazole in an obese patient.

PMID- 21846834
TI  - Earlier response assessment in invasive aspergillosis based on the kinetics of
      serum Aspergillus galactomannan: proposal for a new definition.
AB  - BACKGROUND: Current criteria for assessing treatment response of invasive
      aspergillosis (IA) rely on nonspecific subjective parameters. We hypothesized
      that an Aspergillus-specific response definition based on the kinetics of serum
      Aspergillus galactomannan index (GMI) would provide earlier and more objective
      response assessment. METHODS: We compared the 6-week European Organization for
      Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) response
      criteria with GMI-based response among 115 cancer patients with IA. Success
      according to GMI required survival with repeatedly negative GMI for >=2 weeks.
      Time to response and agreement between the 2 definitions were the study
      endpoints. RESULTS: Success according to EORTC/MSG and GMI criteria was observed
      in 73 patients (63%) and 83 patients (72%), respectively. The GMI-based response
      was determined at a median of 21 days after treatment initiation (range, 15-41
      days), 3 weeks before the EORTC/MSG time point, in 72 (87%) of 83 responders.
      Agreement between definitions was shown in all 32 nonresponders and in 73 of the
      83 responders (91% overall), with an excellent kappa correlation coefficient of
      0.819. Among 10 patients with discordant response (EORTC/MSG failure, GMI
      success), 1 is alive without IA 3 years after diagnosis; for the other,
      aspergillosis could not be detected at autopsy. The presence of other life
      threatening complications in the remaining 8 patients indicates that IA had
      resolved. CONCLUSIONS: The Aspergillus-specific GMI-based criteria compare
      favorably to current response definitions for IA and significantly shorten time
      to response assessment. These criteria rely on a simple, reproducible, objective,
      and Aspergillus-specific test and should serve as the primary endpoint in trials
      of IA.

PMID- 21846835
TI  - The communication orientation model: explaining the diverse effects of sight,
      sound, and synchronicity on negotiation and group decision-making outcomes.
AB  - Two quantitative meta-analyses examined how the presence of visual channels,
      vocal channels, and synchronicity influences the quality of outcomes in
      negotiations and group decision making. A qualitative review of the literature
      found that the effects of communication channels vary widely and that existing
      theories do not sufficiently account for these contradictory findings. To
      parsimoniously encompass the full range of existing data, the authors created the
      communication orientation model, which proposes that the impact of communication
      channels is shaped by communicators' orientations to cooperate or not. Two meta
      analyses-conducted separately for negotiations and decision making-provide strong
      support for this model. Overall, the presence of communication channels (a)
      increased the achievement of high-quality outcomes for communicators with a
      neutral orientation, (b) did not affect the outcomes for communicators with a
      cooperative orientation, but (c) hurt communicators' outcomes with a
      noncooperative orientation. Tests of cross-cultural differences in each meta
      analysis further supported the model: for those with a neutral orientation, the
      beneficial effects of communication channels were weaker within East Asian
      cultures (i.e., Interdependent and therefore more predisposed towards
      cooperation) than within Western cultures (i.e., Independent).

PMID- 21846836
TI  - Human cutaneous leishmaniasis: interferon-dependent expression of double-stranded
      RNA-dependent protein kinase (PKR) via TLR2.
AB  - We investigated the type I interferon (IFN-1)/PKR axis in the outcome of the
      Leishmania (Leishmania) amazonensis infection, along with the underlying
      mechanisms that trigger and sustain this signaling pathway. Reporter assays of
      cell extracts from RAW-264.7 macrophages infected with L. (L.) amazonensis or HEK
      293T cells cotransfected with TLR2 and PKR promoter constructions were employed.
      Primary macrophages of TLR2-knockout (KO) or IFNR-KO mice were infected, and the
      levels of PKR, IFN-1, and superoxide dismutase 1 (SOD1) transcript levels were
      investigated and compared. Immunohistochemical analysis of human biopsy lesions
      was evaluated for IFN-1 and PKR-positive cells. Leishmania infection increased
      the expression of PKR and IFN-beta on induction of PKR-promoter activity. The
      observed effects required the engagement of TLR2. TLR2-KO macrophages expressed
      low IFN-beta and PKR levels postinfection with a reduced parasite load. We also
      revealed the requirement of PKR signaling for Leishmania-induced IFN-1
      expression, responsible for sustaining PKR expression and enhancing infection.
      Moreover, during infection, SOD1 transcripts increased and were also enhanced
      when IFN-1 was added to the cultures. Remarkably, SOD1 expression was abrogated
      in infected, dominant-negative PKR-expressing cells. Finally, lesions of patients
      with anergic diffuse cutaneous leishmaniasis exhibited higher levels of PKR/IFN-1
      expressing cells compared to those with single cutaneous leishmaniasis. In
      summary, we demonstrated the mechanisms and relevance of the IFN-1/PKR axis in
      the Leishmania infection.

PMID- 21846837
TI  - Obesity short-circuits stemness gene network in human adipose multipotent stem
      cells.
AB  - The discovery of adipose multipotent stem cells has provided new insights to
      explore cellular mechanisms involved in adipose tissue function. In the present
      work, we aimed to evaluate how the adipogenic environment influences the stemness
      of the resident multipotent stem cells. To achieve this goal, human omental
      multipotent stem cells (hO-MSCs) were isolated, expanded, and characterized in
      both healthy lean and morbidly obese individuals. We observed decreased cell
      proliferation, premature senescence, and increased cytokine secretion associated
      with increasing body mass index of the patients. Consistent with the latter
      finding, the hO-MSCs derived from patients with morbid obesity lose their
      multilineage differentiation capacity associated with a dysregulation in the Wnt,
      Notch, and Sonic Hedgehog signaling pathways. Moreover, microRNAs involved in the
      regulation of stemness, cell differentiation, and senescence were also up
      regulated in obese individuals. Altogether, our data show that obesity causes a
      general short circuit in the stemness gene network of hO-MSCs.

PMID- 21846838
TI  - Determining the fate of seeded cells in venous tissue-engineered vascular grafts
      using serial MRI.
AB  - A major limitation of tissue engineering research is the lack of noninvasive
      monitoring techniques for observations of dynamic changes in single tissue
      engineered constructs. We use cellular magnetic resonance imaging (MRI) to track
      the fate of cells seeded onto functional tissue-engineered vascular grafts
      (TEVGs) through serial imaging. After in vitro optimization, murine macrophages
      were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles
      and seeded onto scaffolds that were surgically implanted as inferior vena cava
      interposition grafts in SCID/bg mice. Serial MRI showed the transverse relaxation
      times (T(2)) were significantly lower immediately following implantation of USPIO
      labeled scaffolds (T(2) = 44 +/- 6.8 vs. 71 +/- 10.2 ms) but increased rapidly at
      2 h to values identical to control implants seeded with unlabeled macrophages
      (T(2) = 63 +/- 12 vs. 63 +/- 14 ms). This strongly indicates the rapid loss of
      seeded cells from the scaffolds, a finding verified using Prussian blue staining
      for iron containing macrophages on explanted TEVGs. Our results support a novel
      paradigm where seeded cells are rapidly lost from implanted scaffolds instead of
      developing into cells of the neovessel, as traditionally thought. Our findings
      confirm and validate this paradigm shift while demonstrating the first successful
      application of noninvasive MRI for serial study of cellular-level processes in
      tissue engineering.

PMID- 21846839
TI  - Isolation of modulators of the liver-specific organic anion-transporting
      polypeptides (OATPs) 1B1 and 1B3 from Rollinia emarginata Schlecht (Annonaceae).
AB  - Organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are
      liver-specific transporters that mediate the uptake of a broad range of drugs
      into hepatocytes, including statins, antibiotics, and many anticancer drugs.
      Compounds that alter transport by one or both of these OATPs could potentially be
      used to target drugs to hepatocytes or improve the bioavailability of drugs that
      are cleared by the liver. In this study, we applied a bioassay-guided isolation
      approach to identify such compounds from the organic extract of Rollinia
      emarginata Schlecht (Annonaceae). Fractions of the plant extract were screened
      for effects on OATP1B1- and OATP1B3-mediated transport of the model substrates
      estradiol-17beta-glucuronide and estrone-3-sulfate. We isolated three compounds,
      ursolic acid, oleanolic acid, and 8-trans-p-coumaroyloxy-alpha-terpineol, which
      inhibited estradiol-17beta-glucuronide uptake by OATP1B1 but not OATP1B3. In
      addition, a rare compound, quercetin 3-O-alpha-l-arabinopyranosyl(1->2) alpha-L
      rhamnopyranoside, was identified that had distinct effects on each OATP. OATP1B1
      was strongly inhibited, as was OATP1B3-mediated transport of estradiol-17beta
      glucuronide. However, OATP1B3-mediated uptake of estrone-3-sulfate was stimulated
      4- to 5-fold. Kinetic analysis of this stimulation revealed that the apparent
      affinity for estrone-3-sulfate was increased (decreased K(m)), whereas the
      maximal rate of transport (V(max)) was significantly reduced. These results
      demonstrate a mechanism through which the hepatic uptake of drug OATP substrates
      could be stimulated.

PMID- 21846841
TI  - Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial
      dysfunction, caspase activation, and apoptosis in carcinoma cells treated with
      arsenic trioxide.
AB  - Epoxyeicosatrienoic acids (EETs) and the cytochrome P450 epoxygenase CYP2J2
      promote tumorogenesis in vivo and in vitro via direct stimulation of tumor cell
      growth and inhibition of tumor cell apoptosis. Herein, we describe a novel
      mechanism of inhibition of tumor cell apoptosis by EETs. In Tca-8113 cancer
      cells, the antileukemia drug arsenic trioxide (ATO) led to the generation of
      reactive oxygen species (ROS), impaired mitochondrial function, and induced
      apoptosis. 11,12-EET pretreatment increased expression of the antioxidant enzymes
      superoxide dismutase and catalase and inhibited ATO-induced apoptosis. 11,12-EET
      also prevented the ATO-induced activation of p38 mitogen-activated protein
      kinase, c-Jun NH(2)-terminal kinase, caspase-3, and caspase-9. Therefore, 11,12
      EET-pretreatment attenuated the ROS generation, loss of mitochondrial function,
      and caspase activation observed after ATO treatment. Moreover, the CYP2J2
      specific inhibitor compound 26 enhanced arsenic cytotoxicity to a clinically
      relevant concentration of ATO (1-2 MUM). Both the thiol-containing antioxidant, N
      acetyl-cysteine, and 11,12-EET reversed the synergistic effect of the two agents.
      Taken together, these data indicate that 11,12-EET inhibits apoptosis induced by
      ATO through a mechanism that involves induction of antioxidant proteins and
      attenuation of ROS-mediated mitochondrial dysfunction.

PMID- 21846840
TI  - Umami receptor activation increases duodenal bicarbonate secretion via glucagon
      like peptide-2 release in rats.
AB  - Luminal nutrient chemosensing during meal ingestion is mediated by intestinal
      endocrine cells, which regulate secretion and motility via the release of gut
      hormones. We have reported that luminal coperfusion of L-Glu and IMP, common
      condiments providing the umami or proteinaceous taste, synergistically increases
      duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers,
      taste receptor type 1, member 1 (T1R1)/R3. We hypothesized that glucose-dependent
      insulinotropic peptide (GIP) or glucagon-like peptide (GLP) is released by
      duodenal perfusion with L-Glu/IMP. We measured DBS with pH and CO(2) electrodes
      through a perfused rat duodenal loop in vivo. GIP, exendin (Ex)-4 (GLP-1 receptor
      agonist), or GLP-2 was intravenously infused (0.01-1 nmol/kg/h). l-Glu (10 mM)
      and IMP (0.1 mM) were luminally perfused with or without bolus intravenous
      injection (3 or 30 nmol/kg) of the receptor antagonists Pro(3)GIP, Ex-3(9-39), or
      GLP-2(3-33). GIP or GLP-2 infusion dose-dependently increased DBS, whereas Ex-4
      infusion gradually decreased DBS. Luminal perfusion of l-Glu/IMP increased DBS,
      with no effect of Pro(3)GIP or Ex-3(9-39), whereas GLP-2(3-33) inhibited L
      Glu/IMP-induced DBS. Vasoactive intestinal peptide (VIP)(6-28) intravenously or
      N(G)-nitro-L-arginine methyl ester coperfusion inhibited the effect of L-Glu/IMP.
      Perfusion of L-Glu/IMP increased portal venous concentrations of GLP-2, followed
      by a delayed increase of GLP-1, with no effect on GIP release. GLP-1/2 and
      T1R1/R3 were expressed in duodenal endocrine-like cells. These results suggest
      that luminal L-Glu/IMP-induced DBS is mediated via GLP-2 release and receptor
      activation followed by VIP and nitric oxide release. Because GLP-1 is
      insulinotropic and GLP-2 is intestinotrophic, umami receptor activation may have
      additional benefits in glucose metabolism and duodenal mucosal protection and
      regeneration.

PMID- 21846843
TI  - The cover. An architect's table.

PMID- 21846845
TI  - Autism screening strikes emotional chord.

PMID- 21846844
TI  - A piece of my mind. Parallel universe.

PMID- 21846846
TI  - Cultural transformation needed to solve public health problem of chronic pain.

PMID- 21846842
TI  - Monitoring a nuclear factor-kappaB signature of drug resistance in multiple
      myeloma.
AB  - The emergence of acquired drug resistance results from multiple compensatory
      mechanisms acting to prevent cell death. Simultaneous monitoring of proteins
      involved in drug resistance is a major challenge for both elucidation of the
      underlying biology and development of candidate biomarkers for assessment of
      personalized cancer therapy. Here, we have utilized an integrated analytical
      platform based on SDS-PAGE protein fractionation prior to liquid chromatography
      coupled to multiple reaction monitoring mass spectrometry, a versatile and
      powerful tool for targeted quantification of proteins in complex matrices, to
      evaluate a well-characterized model system of melphalan resistance in multiple
      myeloma (MM). Quantitative assays were developed to measure protein expression
      related to signaling events and biological processes relevant to melphalan
      resistance in multiple myeloma, specifically: nuclear factor-kappaB subunits,
      members of the Bcl-2 family of apoptosis-regulating proteins, and Fanconi Anemia
      DNA repair components. SDS-PAGE protein fractionation prior to liquid
      chromatography coupled to multiple reaction monitoring methods were developed for
      quantification of these selected target proteins in amounts of material
      compatible with direct translation to clinical specimens (i.e. less than 50,000
      cells). As proof of principle, both relative and absolute quantification were
      performed on cell line models of MM to compare protein expression before and
      after drug treatment in naive cells and in drug resistant cells; these liquid
      chromatography-multiple reaction monitoring results are compared with existing
      literature and Western blots. The initial stage of a systems biology platform for
      examining drug resistance in MM has been implemented in cell line models and has
      been translated to MM cells isolated from a patient. The ultimate application of
      this platform could assist in clinical decision-making for individualized patient
      treatment. Although these specific assays have been developed to monitor MM,
      these techniques are expected to have broad applicability in cancer and other
      types of disease.

PMID- 21846847
TI  - Erythropoietin in patients with ST-segment elevation myocardial infarction.

PMID- 21846848
TI  - Erythropoietin in patients with ST-segment elevation myocardial infarction.

PMID- 21846849
TI  - Evidence-based treatment and ST-segment elevation myocardial infarction.

PMID- 21846850
TI  - Genomic predictor of survival after chemotherapy for breast cancer.

PMID- 21846851
TI  - Efficacy research and unanswered clinical questions.

PMID- 21846852
TI  - Efficacy and tolerability of pegloticase for the treatment of chronic gout in
      patients refractory to conventional treatment: two randomized controlled trials.
AB  - CONTEXT: Patients with chronic disabling gout refractory to conventional urate
      lowering therapy need timely treatment to control disease manifestations related
      to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)
      conjugated mammalian recombinant uricase, was developed to fulfill this need.
      OBJECTIVE: To assess the efficacy and tolerability of pegloticase in managing
      refractory chronic gout. DESIGN, SETTING, AND PATIENTS: Two replicate,
      randomized, double-blind, placebo-controlled trials (C0405 and C0406) were
      conducted between June 2006 and October 2007 at 56 rheumatology practices in the
      United States, Canada, and Mexico in patients with severe gout, allopurinol
      intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or
      greater. A total of 225 patients participated: 109 in trial C0405 and 116 in
      trial C0406. INTERVENTION: Twelve biweekly intravenous infusions containing
      either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase
      alternating with placebo at successive infusions (monthly treatment group), or
      placebo (placebo group). MAIN OUTCOME MEASURE: Primary end point was plasma uric
      acid levels of less than 6.0 mg/dL in months 3 and 6. RESULTS: In trial C0405 the
      primary end point was reached in 20 of 43 patients in the biweekly group (47%;
      95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%),
      and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04
      for comparisons between biweekly and monthly groups vs placebo, respectively).
      Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly
      group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%
      65%) achieved the primary end point; no placebo-treated patients reached the
      primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When
      data in the 2 trials were pooled, the primary end point was achieved in 36 of 85
      patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the
      monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group
      (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients
      receiving pegloticase and 3 in the placebo group) occurred between randomization
      and closure of the study database (February 15, 2008). CONCLUSION: Among patients
      with chronic gout, elevated serum uric acid level, and allopurinol intolerance or
      refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks
      for 6 months resulted in lower uric acid levels compared with placebo. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00325195.

PMID- 21846853
TI  - Use of radioactive iodine for thyroid cancer.
AB  - CONTEXT: Substantial uncertainty persists about the indications for radioactive
      iodine for thyroid cancer. Use of radioactive iodine over time and the correlates
      of its use remain unknown. OBJECTIVE: To determine practice patterns, the degree
      to which hospitals vary in their use of radioactive iodine, and factors that
      contribute to this variation. DESIGN, SETTING, AND PATIENTS: Time trend analysis
      of radioactive iodine use in a cohort of 189,219 patients with well
      differentiated thyroid cancer treated at 981 hospitals associated with the US
      National Cancer Database between 1990 and 2008. We used multilevel analysis to
      assess the correlates of patient and hospital characteristics on radioactive
      iodine use in the cohort treated from 2004 to 2008. MAIN OUTCOME MEASURE: Use of
      radioactive iodine after total thyroidectomy. RESULTS: Between 1990 and 2008,
      across all tumor sizes, there was a significant increase in the proportion of
      patients with well-differentiated thyroid cancer receiving radioactive iodine
      (1373/3397 [40.4%] vs 11,539/20,620 [56.0%]; P < .001). Multivariable analysis of
      patients treated from 2004 to 2008 found that there was a statistical difference
      in radioactive iodine use between American Joint Committee on Cancer stages I and
      IV (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.31-0.37) but not
      between stages II/III and IV (for stage II vs stage IV, OR, 0.97; 95% CI, 0.88
      1.07 and for stage III vs stage IV, OR, 1.06; 95% CI, 0.95-1.17). In addition to
      patient and tumor characteristics, hospital volume was associated with
      radioactive iodine use. Wide variation in radioactive iodine use existed, and
      only 21.1% of this variation was accounted for by patient and tumor
      characteristics. Hospital type and case volume accounted for 17.1% of the
      variation. After adjusting for available patient, tumor, and hospital
      characteristics, 29.1% of the variance was attributable to unexplained hospital
      characteristics. CONCLUSION: Among patients treated for well-differentiated
      thyroid cancer at hospitals in the National Cancer Database, there was an
      increase in the proportion receiving radioactive iodine between 1990 and 2008;
      much of the variation in use was associated with hospital characteristics.

PMID- 21846854
TI  - Persistent asymptomatic isolated microscopic hematuria in Israeli adolescents and
      young adults and risk for end-stage renal disease.
AB  - CONTEXT: Few data are available on long-term outcomes among adolescents and young
      adults with persistent asymptomatic isolated microscopic hematuria. OBJECTIVE: To
      evaluate the risk of end-stage renal disease (ESRD) in adolescents and young
      adults with persistent asymptomatic isolated microscopic hematuria. DESIGN,
      SETTING, AND PARTICIPANTS: Nationwide, population-based, retrospective cohort
      study using medical data from 1,203,626 persons aged 16 through 25 years (60%
      male) examined for fitness for military service between 1975 and 1997 were linked
      to the Israeli treated ESRD registry. Incident cases of treated ESRD from January
      1, 1980, to May 31, 2010, were included. Cox proportional hazards models were
      used to estimate the hazard ratio (HR) of treated ESRD among those diagnosed as
      having persistent asymptomatic isolated microscopic hematuria. MAIN OUTCOME
      MEASURES: Treated ESRD onset, defined as the date of initiation of dialysis
      treatment or the date of renal transplantation, whichever came first. RESULTS:
      Persistent asymptomatic isolated microscopic hematuria was diagnosed in 3690 of
      1,203,626 eligible individuals (0.3%). During 21.88 (SD, 6.74) years of follow
      up, treated ESRD developed in 26 individuals (0.70%) with and 539 (0.045%)
      without persistent asymptomatic isolated microscopic hematuria, yielding
      incidence rates of 34.0 and 2.05 per 100,000 person-years, respectively, and a
      crude HR of 19.5 (95% confidence interval [CI], 13.1-28.9). A multivariate model
      adjusted for age, sex, paternal country of origin, year of enrollment, body mass
      index, and blood pressure at baseline did not substantially alter the risk
      associated with persistent asymptomatic isolated microscopic hematuria (HR, 18.5
      [95% CI, 12.4-27.6]). A substantially increased risk for treated ESRD attributed
      to primary glomerular disease was found for individuals with persistent
      asymptomatic isolated microscopic hematuria compared with those without the
      condition (incidence rates, 19.6 vs 0.55 per 100,000 person-years, respectively;
      HR, 32.4 [95% CI, 18.9-55.7]). The fraction of treated ESRD attributed to
      microscopic hematuria was 4.3% (95% CI, 2.9%-6.4%). CONCLUSION: Presence of
      persistent asymptomatic isolated microscopic hematuria in persons aged 16 through
      25 years was associated with significantly increased risk of treated ESRD for a
      period of 22 years, although the incidence and absolute risk remain quite low.

PMID- 21846855
TI  - Association between smoking and risk of bladder cancer among men and women.
AB  - CONTEXT: Previous studies indicate that the population attributable risk (PAR) of
      bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women
      and that current cigarette smoking triples bladder cancer risk relative to never
      smoking. During the last 30 years, incidence rates have remained stable in the
      United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person
      years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person
      years); however, changing smoking prevalence and cigarette composition warrant
      revisiting risk estimates for smoking and bladder cancer. OBJECTIVE: To evaluate
      the association between tobacco smoking and bladder cancer. DESIGN, SETTING, AND
      PARTICIPANTS: Men (n = 281,394) and women (n = 186,134) of the National
      Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a
      lifestyle questionnaire and were followed up between October 25, 1995, and
      December 31, 2006. Previous prospective cohort studies of smoking and incident
      bladder cancer were identified by systematic review and relative risks were
      estimated from fixed-effects models with heterogeneity assessed by the I(2)
      statistic. MAIN OUTCOME MEASURES: Hazard ratios (HRs), PARs, and number needed to
      harm (NNH). RESULTS: During 4,518,941 person-years of follow-up, incident bladder
      cancer occurred in 3896 men (144.0 per 100,000 person-years) and 627 women (34.5
      per 100,000 person-years). Former smokers (119.8 per 100,000 person-years; HR,
      2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers
      (177.3 per 100,000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had
      higher risks of bladder cancer than never smokers (39.8 per 100,000 person
      years). In contrast, the summary risk estimate for current smoking in 7 previous
      studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I(2) =
      0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men
      and 0.52 (95% CI, 0.45-0.59) in women. CONCLUSION: Compared with a pooled
      estimate of US data from cohorts initiated between 1963 and 1987, relative risks
      for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher,
      with PARs for women comparable with those for men.

PMID- 21846857
TI  - Real-world imperative of outcomes research.

PMID- 21846856
TI  - Living with an aging parent: "It was a beautiful invitation".
AB  - In the United States and globally, increasing numbers of older parents are living
      with their adult children. Making the decision to live together requires careful
      thought and planning; particularly when the decision means the children will be
      responsible for their elder parents' care, the physicians of all parties should
      be consulted. More than one-third of caregivers state that they seek advice from
      their physician or other clinician when information is needed about this
      transition. Using the case of a couple receiving care from their daughter in her
      own home, we review the prevalence and epidemiology of adult children caring for
      a parent in the adult child's home, important issues to consider, and a framework
      for clinicians to help guide their patients through this transition. We describe
      the physician's ongoing role in caring for and advising both the older parent and
      the adult children during common stages of multigenerational living: before the
      move and during coresidency and subsequent care transitions.

PMID- 21846858
TI  - Challenges facing the US patient-centered outcomes research institute.

PMID- 21846859
TI  - Sharing the financial responsibility of caring for parents.

PMID- 21846860
TI  - The hazards of evidence-based medicine: assessing variations in care.

PMID- 21846861
TI  - Has the time come to include urine dipstick testing in screening asymptomatic
      young adults?

PMID- 21846862
TI  - Skin fragility and blister formation.

PMID- 21846863
TI  - JAMA patient page. Regional anesthesia.

PMID- 21846864
TI  - Letter by patel et Al regarding article "Chromosome 9p21 haplotypes and prognosis
      in white and black patients with coronary artery disease".

PMID- 21846867
TI  - Next-generation genome-wide association studies: time to focus on phenotype?

PMID- 21846868
TI  - ATP6V0A1 polymorphism and microRNA-637: A pathogenetic role for microRNAs in
      essential hypertension at last?

PMID- 21846869
TI  - Are glutathione S-transferase null genotypes "null and void" of risk for ischemic
      vascular disease?

PMID- 21846870
TI  - Recent highlights of metabolomics in cardiovascular research.

PMID- 21846871
TI  - A genome-wide association study in europeans and South asians identifies 5 new
      Loci for coronary artery disease.

PMID- 21846872
TI  - Lack of association of KIF6 genotype with vascular disease and statin response.

PMID- 21846874
TI  - Assessing the influence of mandibular prominence on perceived attractiveness in
      the orthognathic patient, clinician, and layperson.
AB  - The purpose of this investigation was to undertake an objective and quantitative
      evaluation of how mandibular prominence influences perceived attractiveness. The
      mandibular prominence of an idealized profile image was altered in 2 mm
      increments from -16 to 12 mm, in order to represent retrusion and protrusion of
      the mandible, respectively. These images were rated on a 7-point Likert scale by
      a preselected group of pre-treatment orthognathic patients, clinicians, and
      laypeople. A duplicate image was used to assess intra-examiner reliability. From
      the results of this study, it is recommended that in treatment planning to alter
      the sagittal prominence of the mandible in an individual with an otherwise normal
      soft tissue facial profile, an 'ideal' sagittal position with soft tissue
      pogonion on or just behind a true vertical line through subnasale may be used.
      However, mandibular retrusion up to -4 mm or protrusion up to 2 mm was
      essentially unnoticeable. Surgery was desired from mandibular protrusions of
      greater than 3 mm (orthognathic patients and laypeople) and 5 mm (clinicians) and
      retrusions greater than -8 mm. The overall direction of aesthetic opinion
      appeared to be the same for all the observer groups; the greater the retrusion or
      prominence of the lower jaw, the less attractive the perceived attractiveness and
      the greater the desire for surgical correction. Orthognathic patients were found
      to be more critical than laypeople, suggesting that in future studies, greater
      emphasis might be put on evaluating the perceptions of patients as opposed to
      only a lay population.

PMID- 21846875
TI  - Filling without drilling.

PMID- 21846876
TI  - Interatrial electrical dissociation after catheter-based ablation for atrial
      fibrillation and flutter.

PMID- 21846877
TI  - Left-dominant arrhythmogenic cardiomyopathy.

PMID- 21846878
TI  - Charge circuit timeout: a sequence of events leading to failure of an implantable
      cardioverter-defibrillator to deliver therapy.

PMID- 21846879
TI  - Nonfluoroscopic sensor-guided navigation of intracardiac electrophysiology
      catheters within prerecorded cine loops.

PMID- 21846873
TI  - Large-scale candidate gene analysis in whites and African Americans identifies
      IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung,
      and Blood Institute's Candidate Gene Association Resource (CARe) project.
AB  - BACKGROUND: The genetic background of atrial fibrillation (AF) in whites and
      African Americans is largely unknown. Genes in cardiovascular pathways have not
      been systematically investigated. METHODS AND RESULTS: We examined a panel of
      approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095
      cardiovascular candidate genes and AF in 3 cohorts with participants of European
      (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the
      National Heart, Lung, and Blood Institute's Candidate Gene Association Resource.
      Results in whites were followed up in the German Competence Network for AF
      (n=906, 468 cases). The top result was assessed in relation to incident ischemic
      stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke
      Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R
      gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence
      interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical
      significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P=0.09). The
      results were comparable in the German AF Network replication, (RR, 0.71; 95% CI,
      0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in
      whites. The known chromosome 4 locus near PITX2 in whites also was associated
      with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69;
      P=0.0005). CONCLUSIONS: In a community-based cohort meta-analysis, we identified
      genetic association in IL6R with AF in whites. Additionally, we demonstrated that
      the chromosome 4 locus known from recent genome-wide association studies in
      whites is associated with AF in African Americans.

PMID- 21846880
TI  - Recurrent perimitral tachycardia using epicardial coronary sinus connection to
      bypass endocardial conduction block at the mitral isthmus.

PMID- 21846881
TI  - Epicardial-only block during endocardial mitral isthmus ablation facilitated by
      coronary sinus occlusion.

PMID- 21846882
TI  - Atrial tachycardia originating from the junction of the right atrium and a
      diverticulum of the inferior vena cava.

PMID- 21846883
TI  - Does a Brugada pattern ECG precipitated by excessive-dose flecainide provide a
      diagnosis of a Brugada syndrome patient and/or contraindicate its use? A case
      study.

PMID- 21846885
TI  - Exercise, stand up, flip a coin, or just say no: provocative testing in the child
      with borderline QTc.

PMID- 21846886
TI  - Shocks: the whole truth, the partial truth, or nowhere near the truth.

PMID- 21846887
TI  - Complex fractionated atrial electrograms: is this the beast to tame in atrial
      fibrillation?

PMID- 21846888
TI  - A surgical option for ventricular tachycardia caused by nonischemic
      cardiomyopathy.

PMID- 21846890
TI  - Acute liver failure associated with dronedarone.

PMID- 21846889
TI  - Advances in cardiac ATP-sensitive K+ channelopathies from molecules to
      populations.

PMID- 21846891
TI  - Bilateral branch pulmonary artery melody valve implantation for treatment of
      complex right ventricular outflow tract dysfunction in a high-risk patient.

PMID- 21846893
TI  - Letter by Santos et al regarding article, "Pharmacodynamic effects of different
      aspirin dosing regimens in type 2 diabetes mellitus patients with coronary artery
      disease".

PMID- 21846896
TI  - Plugging holes: expanding horizon for structural interventions.

PMID- 21846897
TI  - Cardioprotection of insulin-like growth factor-1 during reperfusion therapy: what
      is the underlying mechanism or mechanisms?

PMID- 21846898
TI  - Transcatheter aortic valve implantation: current principles of patient and
      technique selection and future perspectives.

PMID- 21846899
TI  - Transseptal implantation of a transcatheter heart valve in a mitral annuloplasty
      ring to treat mitral repair failure.

PMID- 21846900
TI  - A rare cause of late drug-eluting stent thrombosis unraveled by optical coherence
      tomography.

PMID- 21846901
TI  - Alternative activation of macrophages by IL-4 enhances the proteolytic capacity
      of their phagosomes through synergistic mechanisms.
AB  - Alternatively activated macrophages, generated in a T-helper 2 environment, have
      demonstrated roles in wound repair and tissue remodeling in addition to being
      charged with immune tasks. Because the hydrolytic chemistries of the phagosomal
      lumen are central to many of these functions, we investigated their modification
      after alternative activation with IL-4 and IL-13. Most significantly, we found
      striking up-regulation of the proteolytic levels within the phagosome of IL-4
      activated macrophages. Two synergistic mechanisms were determined to underlie
      this up-regulation. First, IL-4-activated macrophages displayed increased
      expression of cathepsin S and L, providing greater proteolytic machinery to the
      phagosome despite unchanged rates of lysosomal contribution. Secondly, decreased
      phagosomal NADPH oxidase (NOX2) activity, at least partially resulting from
      decreased expression of the NOX2 subunit gp91(phox), resulted in a more reductive
      lumenal microenvironment, which in turn, enhanced activities of local cysteine
      cathepsins. Decreased NOX2 activity additionally increased the phagosome's
      ability to reduce disulfides, further enhancing the efficiency of the macrophage
      to degrade proteins containing disulfide bonds. Together, these changes initiated
      by IL-4 act synergistically to rapidly and dramatically enhance the macrophage's
      ability to degrade phagocytosed protein, which, we reason, better equips this
      cell for its roles in wound repair and tissue remodeling.

PMID- 21846902
TI  - Malignancies occurring during therapy with tyrosine kinase inhibitors (TKIs) for
      chronic myeloid leukemia (CML) and other hematologic malignancies.
AB  - Success of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML)
      has given patients hope for a long disease-free-survival. A longer survival
      raises the question of late effects, including development of another malignancy.
      Records of 1445 patients with CML/myeloproliferative neoplasm or other
      hematologic malignancies treated with TKIs were reviewed to investigate frequency
      and characteristics of second malignancies (other than acute myeloid leukemia,
      acute lymphocytic leukemia, or myelodysplastic syndrome). The number of second
      cancers was compared with the number expected from the Surveillance,
      Epidemiology, and End Results database. After a median follow-up of 107 months
      (range, 13-362 months) after CML/myeloproliferative neoplasm diagnosis, 66
      patients (4.6%) developed 80 second cancers, including skin (31%), prostate
      (15%), melanoma (13%), digestive system (10%), kidney (4%), thyroid (4%), breast
      (3%), chronic lymphocytic leukemia (3%), hepatobiliary (3%), and other cancers
      (14%). Excluding nonmelanoma skin cancers, 55 second cancers were seen in 51
      (3.5%) of all patients treated. The risk of second cancer was lower than expected
      (observed-to-expected ratio, 0.6; 95% confidence interval, 0.44-0.81). Second
      cancers occur in a small percentage of patients receiving therapy with TKIs for
      hematologic malignancies, mostly CML. No evidence at the moment suggests that
      exposure to TKIs increases the risk of developing second cancers.

PMID- 21846903
TI  - Apelin and the proopiomelanocortin system: a new regulatory pathway of
      hypothalamic alpha-MSH release.
AB  - Neuronal networks originating in the hypothalamic arcuate nucleus (Arc) play a
      fundamental role in controlling energy balance. In the Arc, neuropeptide Y (NPY)
      producing neurons stimulate food intake, whereas neurons releasing the
      proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone
      (alpha-MSH) strongly decrease food intake. There is growing evidence to suggest
      that apelin and its receptor may play a role in the central control of food
      intake, and both are concentrated in the Arc. We investigated the presence of
      apelin and its receptor in Arc NPY- and POMC-containing neurons and the effects
      of apelin on alpha-MSH release in the hypothalamus. We showed, by
      immunofluorescence and confocal microscopy, that apelin-immunoreactive (IR)
      neuronal cell bodies were distributed throughout the rostrocaudal extent of the
      Arc and that apelin was strongly colocalized with POMC, but weakly colocalized
      with NPY. However, there were numerous NPY-IR nerve fibers close to the apelin-IR
      neuronal cell bodies. By combining in situ hybridization with
      immunohistochemistry, we demonstrated the presence of apelin receptor mRNA in Arc
      POMC neurons. Moreover, using a perifusion technique for hypothalamic explants,
      we demonstrated that apelin-17 (K17F) increased alpha-MSH release, suggesting
      that apelin released somato-dendritically or axonally from POMC neurons may
      stimulate alpha-MSH release in an autocrine manner. Consistent with these data,
      hypothalamic apelin levels were found to be higher in obese db/db mice and fa/fa
      Zucker rats than in wild-type animals. These findings support the hypothesis that
      central apelin is involved in regulating body weight and feeding behavior through
      the direct stimulation of alpha-MSH release.

PMID- 21846904
TI  - Effects of aerobic vs. resistance training on visceral and liver fat stores,
      liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE
      AT/RT.
AB  - While the benefits of exercise are clear, many unresolved issues surround the
      optimal exercise prescription. Many organizations recommend aerobic training (AT)
      and resistance training (RT), yet few studies have compared their effects alone
      or in combination. The purpose of this study, part of Studies Targeting Risk
      Reduction Interventions Through Defined Exercise-Aerobic Training and/or
      Resistance Training (STRRIDE/AT/RT), was to compare the effects of AT, RT, and
      the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting
      insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial,
      249 subjects [18-70 yr old, overweight, sedentary, with moderate dyslipidemia
      (LDL cholesterol 130-190 mg/dl or HDL cholesterol <= 40 mg/dl for men or <= 45
      mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished
      the run-in and were randomized into one of the following 8-mo exercise-training
      groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/exercise, 8-12
      repetitions/set, 2) AT, which was equivalent to ~19.2 km/wk (12 miles/wk) at 75%
      peak O(2) uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing
      the intervention. The primary outcome variables were as follows: visceral and
      liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant
      reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total
      and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in
      subcutaneous abdominal fat (P < 0.05) but did not significantly improve the other
      variables. AT was more effective than RT at improving visceral fat, liver-to
      spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater
      reduction in liver fat score (P < 0.10). The effects of AT/RT were statistically
      indistinguishable from the effects of AT. These data show that, for overweight
      and obese individuals who want to reduce measures of visceral fat and fatty liver
      infiltration and improve HOMA and alanine aminotransferase, a moderate amount of
      aerobic exercise is the most time-efficient and effective exercise mode.

PMID- 21846905
TI  - The phospholipid monolayer associated with perilipin-enriched lipid droplets is a
      highly organized rigid membrane structure.
AB  - The significance of lipid droplets (LD) in lipid metabolism, cell signaling, and
      membrane trafficking is increasingly recognized, yet the role of the LD
      phospholipid monolayer in LD protein targeting and function remains unknown. To
      begin to address this issue, two populations of LD were isolated by ConA
      sepharose affinity chromatography: 1) functionally active LD enriched in
      perilipin, caveolin-1, and several lipolytic proteins, including ATGL and HSL;
      and 2) LD enriched in ADRP and TIP47 that contained little to no lipase activity.
      Coimmunoprecipitation experiments confirmed the close association of caveolin and
      perilipin and lack of interaction between caveolin and ADRP, in keeping with the
      separation observed with the ConA procedure. The phospholipid monolayer structure
      was evaluated to reveal that the perilipin-enriched LD exhibited increased
      rigidity (less fluidity), as shown by increased cholesterol/phospholipid,
      Sat/Unsat, and Sat/MUFA ratios. These results were confirmed by DPH-TMA, NBD
      cholesterol, and NBD-sphingomyelin fluorescence polarization studies. By
      structure and organization, the perilipin-enriched LD most closely resembled the
      adipocyte PM. In contrast, the ADRP/TIP47-enriched LD contained a more fluid
      monolayer membrane, reflecting decreased polarizations and lipid order based on
      phospholipid fatty acid analysis. Taken together, results indicate that perilipin
      and associated lipolytic enzymes target areas in the phospholipid monolayer that
      are highly organized and rigid, similar in structure to localized areas of the PM
      where cholesterol and fatty acid uptake and efflux occur.

PMID- 21846907
TI  - Mechanism for antioxidative effects of thiazolidinediones in pancreatic beta
      cells.
AB  - Thiazolidinediones (TZDs) are synthetic ligands of peroxisome proliferator
      activated receptor-gamma (PPARgamma), a member of the nuclear receptor
      superfamily. TZDs are known to increase insulin sensitivity and also to have an
      antioxidative effect. In this study, we tested whether TZDs protect pancreatic
      beta-cells from oxidative stress, and we investigated the mechanism involved in
      this process. To generate oxidative stress in pancreatic beta-cells (INS-1 and
      betaTC3) or isolated islets, glucose oxidase was added to the media. The
      extracellular and intracellular reactive oxygen species (ROS) were measured to
      directly determine the antioxidant effect of TZDs. The phosphorylation of
      JNK/MAPK after oxidative stress was detected by Western blot analysis, and
      glucose-stimulated insulin secretion and cell viability were also measured. TZDs
      significantly reduced the ROS levels that were increased by glucose oxidase, and
      they effectively prevented beta-cell dysfunction. The antioxidative effect of
      TZDs was abolished in the presence of a PPARgamma antagonist, GW9662. Real-time
      PCR was used to investigate the expression levels of antioxidant genes. The
      expression of catalase, an antioxidant enzyme, was increased by TZDs in
      pancreatic beta-cells, and the knockdown of catalase significantly inhibited the
      antioxidant effect of TZDs. These results suggest that TZDs effectively protect
      pancreatic beta-cells from oxidative stress, and this effect is dependent largely
      on PPARgamma. In addition, the expression of catalase is increased by TZDs, and
      catalase, at least in part, mediates the antioxidant effect of TZDs in pancreatic
      beta-cells.

PMID- 21846906
TI  - Promyelocytic leukemia inhibits adipogenesis, and loss of promyelocytic leukemia
      results in fat accumulation in mice.
AB  - The function of the tumor suppressor promyelocytic leukemia (PML) protein is
      disrupted in promyelocytic leukemia. PML has been reported to function as a
      negative regulator of mTOR (mammalian target of rapamycin) and nuclear Akt under
      some conditions. mTOR and Akt pathways regulate a diverse array of pathways,
      including those that control insulin signaling, energy metabolism, growth,
      cellular survival, and lifespan. Although the PML-mTOR/Akt link suggests that PML
      may have metabolic functions in the whole organism, very little is known about
      the metabolic functions of PML. Here we report that PML(-/-) mice did not show
      any significant metabolic defects. There was no impairment in the mTOR/Akt or
      AMPK signaling in white adipose tissue, liver, or muscle. However, despite having
      normal food intake and activity levels, PML(-/-) mice gained body weight faster
      and had more fat mass, particularly subcutaneous fat mass, in the diet-induced
      obesity model. Using in vitro adipogenesis models, we discovered that PML is a
      suppressor of adipogenesis. PML expression decreased during adipogenesis and was
      undetectable in fully differentiated adipocytes. Loss of PML increased expression
      of the adipogenic transcription factors CCAAT/enhancer binding protein-alpha and
      peroxisome proliferator-activated receptor-gamma. We found that the Sirt1-NCor
      SMRT corepressor complex, which represses pparg transcription, does not bind to
      the pparg promoter efficiently upon PML depletion. On the basis of these
      findings, we propose that PML is a negative regulator of the adipogenic
      transcription factors and that, in times of energy excess, PML may limit fat
      accumulation by suppressing the differentiation of preadipocytes into adipocytes.

PMID- 21846908
TI  - Acquired activated protein C resistance caused by lupus anticoagulants.
AB  - Lupus anticoagulants (LA) can cause acquired activated protein C resistance (APC
      R), but the clinical significance is unclear. To investigate thrombosis and
      acquired APC-R in patients with LA, we enrolled all 132 patients undergoing
      hypercoagulability testing with positive LA results and in whom APC-R (with
      factor V-deficient plasma) was performed during a 2.5-year period. Among 121
      patients without factor V Leiden, 24.0% had acquired APC-R; retrospective and
      prospective (mean follow-up, 2.0 years) thrombotic events were analyzed. The
      distribution of venous vs arterial thrombosis was different for APC-R vs no APC-R
      (P = .0064). The majority (19/29 [66%]) with acquired APC-R experienced venous
      thrombosis, whereas a minority experienced arterial thrombosis (9/29 [31%]; P =
      .017). The opposite pattern occurred among patients without APC-R (arterial
      thrombi more common than venous thrombi). After excluding thrombotic events more
      than 5 years from a positive LA test, venous thrombosis occurred in 62% with
      (18/29) vs 32% without (29/92) APC-R (P = .0045); and arterial thrombosis in 28%
      with (8/29) vs 51% without (47/92) APC-R (P = .033). Patients with acquired APC-R
      due to LA had more venous thrombosis than did patients with LA without APC-R and
      experienced venous more often than arterial thrombosis.

PMID- 21846909
TI  - Diagnostic usefulness of a lumi-aggregometer adenosine triphosphate release assay
      for the assessment of platelet function disorders.
AB  - Platelet dense granule release assays are recommended for diagnosing platelet
      function disorders and are commonly performed by Lumi-Aggregometer (Chrono-Log,
      Havertown, PA) assays of adenosine triphosphate (ATP) release. We conducted a
      prospective cohort study of people tested for ATP release defects to assess
      bleeding symptoms. Reduced release, with 1 or more agonists, was more common
      among patients with bleeding disorders than among healthy control subjects (P <
      .001). The respective likelihood (odds ratio [95% confidence interval]) of a
      bleeding disorder or an inherited platelet function disorder were high when
      release was reduced with 1 or more agonists (17 [6-46]; 128 [30-545]), even if
      aggregation was normal (12 [4-34]; 105 [20-565]). ATP release had high
      specificity and moderate sensitivity for inherited platelet function disorders,
      with most abnormalities detected by the combination of 6 MUmol/L epinephrine, 5.0
      MUg/mL collagen, and 1 MUmol/L U46619. Platelet ATP release assays are useful for
      evaluating common bleeding disorders, regardless of aggregation findings.

PMID- 21846910
TI  - Strict vs lenient criteria for elution testing: comparison of yields between two
      tertiary care medical centers.
AB  - In this study, 2 patient populations, using different elution strategies, were
      compared to evaluate eluate yields under more and less restrictive conditions. An
      informative eluate was defined as one in which an antibody that could be
      clinically significant was detected in the eluate but was not detectable in the
      plasma at the time of elution testing. The results for 160 direct antiglobulin
      tests (DATs) and 160 elution studies were evaluated in 71 patients at the adult
      hospital (lenient criteria). The results for 372 DATs and 43 elution studies were
      evaluated in 123 patients at the pediatric hospital (strict criteria). The yields
      from these eluates were 0.6% at the adult hospital (C antibody) vs 2.3% at the
      pediatric hospital (Jk(a) antibody). Thus, the yield of information from eluate
      testing is low regardless of the stringency applied to testing. However,
      considering the cost and time required for testing, more stringent criteria are
      advised.

PMID- 21846911
TI  - Frequency and characteristics of coagulopathy in trauma patients treated with a
      low- or high-plasma-content massive transfusion protocol.
AB  - A massive transfusion protocol (MTP) in which most non-RBC transfusions were
      laboratory result-driven was updated to a 1:1:1 RBC/plasma/platelet formula
      driven protocol. Platelet count, fibrinogen level, and prothrombin time (PT) were
      monitored. In the patients who survived the first 12 hours, the results of
      coagulation tests were analyzed. Irrespective of the MTP or transfused RBC/plasma
      ratio, a majority of patients became coagulopathic, usually within the first 2
      hours, and a fibrinogen deficiency (fibrinogen level, <100 mg/dL [2.9 MUmol/L])
      was almost always the initial abnormality. The laboratory value trends under each
      MTP were indistinguishable: PTs were prolonged and platelet counts and fibrinogen
      levels fell during the first 100 minutes and then corrected back toward baseline.
      More than 80% of patients in each group were noncoagulopathic at 12 hours. A
      1:1:1 formula-driven MTP did not affect the frequency, nature, or duration of
      coagulopathy according to laboratory test results.

PMID- 21846912
TI  - Laboratory testing for Clostridium difficile infection: light at the end of the
      tunnel.
AB  - Clostridium difficile infection (CDI) is changing as evidenced by increasing
      virulence, rising incidence, unresponsiveness to metronidazole therapy, and worse
      outcomes. Thus, it is critical that CDI diagnosis be accurate so ongoing
      epidemiology, disease prevention, and treatment remain satisfactory. We tested 10
      diagnostic assays, including 1 commercial real-time polymerase chain reaction
      (qPCR) test for the laboratory detection of toxigenic C difficile on 1,000 stool
      samples. Sensitive culture for toxigenic C difficile using 2 types of media with
      broth enrichment defined the reference standard. For the study, 1,000 tests were
      performed on samples from 919 patients. Of the samples, 146 contained evidence
      for toxigenic C difficile and represented the true-positive results. Only the US
      Food and Drug Administration-cleared qPCR assay (Becton Dickinson, Franklin
      Lakes, NJ) and 1 glutamate dehydrogenase test (TechLab, Blacksburg, VA) were not
      statistically inferior to culture in sensitivity. The common enzyme immunoassay
      tests all had sensitivity values less than 50%. Clinical laboratory professionals
      need to seriously consider their diagnostic testing and use the assays that
      perform best for the detection of CDI.

PMID- 21846913
TI  - Evaluation of a selection strategy before use of 16S rRNA gene sequencing for the
      identification of clinically significant gram-negative rods and coccobacilli.
AB  - Although 16S ribosomal RNA (rRNA) gene sequencing is well established for
      correctly identifying bacteria, its most efficient use in a routine clinical
      laboratory is not clear. We devised and evaluated a strategy to select gram
      negative rods and coccobacilli (GNRCB) for which sequencing might be necessary
      before routine identification methods had been exhausted. The prospectively
      applied selection criteria were primarily based on the isolate's display of
      unusual or discordant phenotypic results and/or disease correlation. By using
      this strategy, we selected a total of 120 GNRCB (representing only ~2% of all
      identified). The strategy was demonstrated to be efficient because the
      preliminary phenotypic identification for 79.2% of those isolates needed revision
      (18.2% were novel and about a third would have required further extensive
      testing). The knowledge that 1.6% (ie, 79% of 2%) of isolated GNRCB might benefit
      from sequence identification could provide guidelines for routine clinical
      laboratories toward efficient use of sequence analysis.

PMID- 21846914
TI  - An assessment of the usefulness of immunohistochemical stains in the diagnosis of
      hairy cell leukemia.
AB  - Annexin-1 and T-bet are recently described immunohistochemical stains that
      reportedly assist in the diagnosis of hairy cell leukemia (HCL). Our objective
      was to assess the sensitivity and specificity of a panel of immunohistochemical
      stains in distinguishing HCL from other B-cell neoplasms, particularly splenic
      and extranodal marginal zone lymphomas (SMZL and ENMZL, respectively). The study
      included 234 bone marrow biopsy specimens: 101 HCL, 13 SMZL, and 10 ENMZL cases
      were assessed with CD20, tartrate-resistant acid phosphatase (TRAP), DBA.44, a-1,
      T-bet, and cyclin D1, and 110 control cases were assessed with annexin-1 and T
      bet. Our study showed that annexin-1 is a specific and sensitive marker for HCL;
      however, interpretation is limited by positivity within myeloid precursors. T
      bet, DBA.44, and TRAP immunohistochemical stains lack sufficient sensitivity and
      specificity to differentiate HCL from either form of marginal zone lymphoma.
      However, our data suggest that the addition cyclin D1 to the immunostaining panel
      will increase the sensitivity and specificity of HCL diagnosis.

PMID- 21846915
TI  - The diagnostic value of CD1d expression in a large cohort of patients with B-cell
      chronic lymphoproliferative disorders.
AB  - Immunophenotyping is indispensable in the differential diagnosis of B-cell
      chronic lymphoproliferative disorders (B-CLPDs). However, B-CLPDs often show
      overlapping immunophenotypic profiles and may be diagnostically challenging. CD1d
      is an HLA class I-like molecule that presents glycolipids to invariant natural
      killer T cells. Normal mature B cells constitutively express CD1d, but with the
      exception of some conflicting data, its expression in B-CLPDs is unknown. We
      demonstrate that in 222 B-CLPD cases, CD1d expression of less than 45% is
      strongly predictive of CLL (likelihood ratio, 32.3; specificity, 97.4%;
      sensitivity, 84.1%). In addition, CD1d showed significantly higher staining
      intensity in splenic marginal zone lymphoma compared with atypical hairy cell
      leukemia, lymphoplasmacytic lymphoma, and mantle cell lymphoma, thus allowing the
      discrimination of the former from the latter immunophenotypically overlapping B
      CLPDs. It is important to note that in a given patient, CD1d expression on
      malignant B cells was similar between tissues and remained unaffected by disease
      stage and treatment status. Our findings strongly argue for the incorporation of
      CD1d into routine lymphoma panels.

PMID- 21846916
TI  - Pulmonary histoplasmosis producing a spindle cell "pseudotumor".
AB  - Pulmonary spindle cell proliferations have been reported in association with a
      limited group of infectious agents. These lesions are rare and identified most
      often in the setting of immunosuppression. Because their appearance can simulate
      a spindle cell neoplasm, they are diagnostically treacherous, sometimes delaying
      antimicrobial therapy or resulting in unnecessary surgery. We report a case of a
      spindle pseudotumor of the lung resulting from Histoplasma capsulatum infection,
      a previously unreported cause of a spindle cell lesion in the lung. The patient
      was a 67-year-old woman in whom positron emission tomography-positive nodules
      developed in the left lung and left mediastinum. The patient had undergone renal
      transplantation and was receiving immunosuppressive therapy with mycophenolate,
      tacrolimus, and low-dose prednisone. Infection with H capsulatum was confirmed by
      culture of pleural effusion fluid, DNA probe analysis of the pleural fluid
      culture isolate, urinary Histoplasma antigen detection, and Grocott methenamine
      silver stains of tissue sections. To our knowledge, this is the first case of a
      spindle cell "pseudotumor" of the lung resulting from histoplasmosis. It
      highlights the importance of performing special stains for organisms when
      evaluating pulmonary spindle cell lesions in an immunocompromised host.

PMID- 21846917
TI  - Evidence of Renal Infection in Fatal Cases of 2009 Pandemic Influenza A (H1N1).
AB  - The 2009 pandemic influenza A (H1N1) caused significant morbidity and mortality.
      Acute lung injury is the hallmark of the disease, but multiple organ system
      dysfunction can develop and lead to death. Therefore, we sought to investigate
      whether there was postmortem evidence of H1N1 presence and virus-induced organ
      injury in autopsy specimens. Five cases in which patients died of influenza A
      (H1N1) virus infection were studied. The lungs of all patients showed macroscopic
      and microscopic findings already described for H1N1 (consolidation, edema,
      hemorrhage, alveolar damage, hyaline membrane, and inflammation), and H1N1
      viruses were present in alveolar cells in immunochemical studies. Acute tubular
      necrosis was present in all cases, but there was no evidence of direct virus
      induced kidney injury. Nevertheless, H1N1 viruses were found in the cytoplasm of
      glomerular macrophages in the kidneys of 4 patients. Therefore, our data provide
      strong evidence that H1N1 presence is not restricted to the lungs.

PMID- 21846918
TI  - Cystic neutrophilic granulomatous mastitis: an underappreciated pattern strongly
      associated with gram-positive bacilli.
AB  - Although granulomatous lobular mastitis is associated with gram-positive bacilli
      such as Corynebacterium, this association is not well known. We report 3 cases of
      mastitis caused by gram-positive bacilli. All 3 abscesses were suppurative with
      distinct enlarged cystic spaces in which rare gram-positive bacilli were
      identified. Two cases were also granulomatous. Cultures in all 3 cases were
      negative. All 3 patients recovered after biopsy and tetracycline-based therapy.
      Infection in the breast by gram-positive bacilli is associated with a distinct
      histologic pattern, including cystic spaces in the setting of
      neutrophilic/granulomatous inflammation that can be recognized and should prompt
      careful search for the organism within enlarged vacuoles.

PMID- 21846919
TI  - NY-BR-1 and PAX8 immunoreactivity in breast, gynecologic tract, and other CK7+
      carcinomas: potential use for determining site of origin.
AB  - The distinction between breast and mullerian carcinomas from each other and from
      tumors with a similar cytokeratin profile can be difficult. We tested the
      usefulness of 2 new markers, NY-BR-1 and PAX8, by staining a variety of breast
      and gynecologic carcinomas, along with tumors of pancreas, bile ducts, stomach,
      and gastroesophageal junction. NY-BR-1 expression (ie, H score >10) was seen in
      58.4% of breast carcinomas (111/190), 5.6% of mullerian carcinomas (8/142), 7% of
      pancreatic tumors (1/15), 0% of cholangiocarcinomas (0/22), 0% of gastric tumors
      (0/36), and 0% of gastroesophageal carcinomas (0/25). All 188 breast carcinomas
      were negative for PAX8. PAX8 expression was seen in 72.4% of mullerian tumors
      (105/145). All pancreatic tumors (n = 15), cholangiocarcinomas (n = 23), and
      gastric (n = 35) and gastroesophageal junction (n = 25) carcinomas were negative
      for PAX8. Addition of NY-BR-1 and PAX8 in a panel would be useful in
      distinguishing breast cancer, gynecologic tumors, and tumors of the upper
      gastrointestinal tract.

PMID- 21846920
TI  - Microcystic squamous cell carcinoma of the lung: a clinicopathologic study of
      three cases.
AB  - Three cases of pulmonary squamous cell carcinoma (SCC) are described displaying a
      prominent microcystic pattern closely resembling microcystic adnexal carcinoma of
      the skin (MAC). The patients were 2 women and 1 man aged 72 to 83 years.
      Histologically, in addition to conventional SCC, all tumors showed striking
      microcystic changes characterized by nests and strands of basaloid squamous cells
      with central cystic spaces, peripheral palisading, and cytoplasmic clearing of
      the central tumor portions. Follow-up available for 2 patients revealed that 1
      was alive at 76 months and 1 had died 38 months after diagnosis. Microcystic SCC
      is an unusual variant of SCC of the lung histologically mimicking tumors with
      glandular or adnexal differentiation and a particularly striking resemblance to
      MAC of the skin. The importance of the recognition of this growth pattern lies in
      the separation from other often less aggressive pulmonary neoplasms or metastatic
      disease from a cutaneous tumor.

PMID- 21846921
TI  - Identification of malignant cytologic criteria in pancreatobiliary brushings with
      corresponding positive fluorescence in situ hybridization results.
AB  - Cytologic evaluation of pancreatobiliary brushings is specific but poorly
      sensitive for malignancy. Detection of polysomic cells by fluorescence in situ
      hybridization (FISH) is significantly more sensitive than routine cytology with
      similar specificity. The purpose of this study was to identify cytologic criteria
      most associated with malignancy in specimens unaffected by sample failure.
      Endoscopic brushings were split equally for routine cytologic and FISH analyses
      per clinical practice. We retrospectively evaluated 16 cytologic criteria on
      Papanicolaou-stained slides. We assumed that the presence of polysomic cells by
      FISH indicated successful tumor sampling in specimens from patients with
      pathologic evidence of malignancy on follow-up. We compared cytologic criteria of
      malignant brushings with corresponding positive FISH results (positive control, n
      = 39) with those without evidence of malignancy and corresponding negative FISH
      results (negative control, n = 30). The presence of single abnormal cells,
      irregular nuclear membranes, and enlarged nuclei were independent predictors of
      malignancy by logistic regression (P < .05).

PMID- 21846922
TI  - Anastomosing hemangioma of the genitourinary system: eight cases in the kidney
      and ovary with immunohistochemical and ultrastructural analysis.
AB  - We describe 3 ovarian and 5 renal anastomosing hemangiomas. One manifested with
      polycythemia, others were incidental; none recurred. The mean patient age was 58
      years. Three hemangiomas developed in end-stage renal disease. Tumors were well
      demarcated, mahogany brown, spongy lesions measuring 0.1 to 5 cm. Tortuous large
      vessels fed and drained tightly packed anastomosing sinusoidal capillary
      channels. Four hemangiomas exhibited lobular architecture, central
      edema/hyalinization, and intravascular growth. Five cases had thrombosis,
      hemorrhage, and hemosiderin. One ovarian tumor induced stromal luteinization.
      Three tumors had foci of extramedullary hematopoiesis (one associated with
      polycythemia). Six cases demonstrated eosinophilic intracytoplasmic globules.
      Three cases included hobnail endothelial cells. Atypia was minimal and mitoses
      were absent in all cases. We find this vascular neoplasm unique for the
      genitourinary system. Despite selected features mimicking angiosarcoma, our data
      support its benign nature. The current study expands the gross and radiographic
      appearance, clinical aspects, and ultrastructure, with the first report of the
      lesion occurring in the ovary.

PMID- 21846923
TI  - Chlamydia psittaci infection in nongastrointestinal MALT lymphomas and their
      precursor lesions.

PMID- 21846924
TI  - Coexisting follicular and mantle cell lymphoma with each having an in situ
      component.

PMID- 21846925
TI  - Growth factor and catabolic cytokine concentrations are influenced by the
      cellular composition of platelet-rich plasma.
AB  - BACKGROUND: Previous studies of bioactive molecules in platelet-rich plasma (PRP)
      have documented growth factor concentrations that promote tissue healing.
      However, the effects of leukocytes and inflammatory molecules in PRP have not
      been defined. HYPOTHESIS: The hypothesis for this study was that the
      concentration of growth factors and catabolic cytokines would be dependent on the
      cellular composition of PRP. STUDY DESIGN: Controlled laboratory study. METHODS:
      Platelet-rich plasma was made from 11 human volunteers using 2 commercial
      systems: Arthrex ACP (Autologous Conditioned Plasma) Double Syringe System (PRP
      1), which concentrates platelets and minimizes leukocytes, and Biomet GPS III
      Mini Platelet Concentrate System (PRP-2), which concentrates both platelets and
      leukocytes. Transforming growth factor-beta1 (TGF-beta1), platelet-derived growth
      factor-AB (PDGF-AB), matrix metalloproteinase-9 (MMP-9), and interleukin-1beta
      (IL-1beta) were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The PRP-1 system consisted of concentrated platelets (1.99*) and diminished
      leukocytes (0.13*) compared with blood, while PRP-2 contained concentrated
      platelets (4.69*) and leukocytes (4.26*) compared with blood. Growth factors were
      significantly increased in PRP-2 compared with PRP-1 (TGF-beta1: PRP-2 = 89
      ng/mL, PRP-1 = 20 ng/mL, P < .05; PDGF-AB: PRP-2 = 22 ng/mL, PRP-1 = 6.4 ng/mL, P
      < .05). The PRP-1 system did not have a higher concentration of PDGF-AB compared
      with whole blood. Catabolic cytokines were significantly increased in PRP-2
      compared with PRP-1 (MMP-9: PRP-2 = 222 ng/mL, PRP-1 = 40 ng/mL, P < .05; IL
      1beta: PRP-2 = 3.67 pg/mL, PRP-1 = 0.31 pg/mL, P < .05). Significant, positive
      correlations were found between TGF-beta1 and platelets (r(2) = .75, P < .001),
      PDGF-AB and platelets (r(2) = .60, P < .001), MMP-9 and neutrophils (r(2) = .37,
      P < .001), IL-1beta and neutrophils (r(2) = .73, P < .001), and IL-1beta and
      monocytes (r(2) = .75, P < .001). CONCLUSION: Growth factor and catabolic
      cytokine concentrations were influenced by the cellular composition of PRP.
      Platelets increased anabolic signaling and, in contrast, leukocytes increased
      catabolic signaling molecules. Platelet-rich plasma products should be analyzed
      for content of platelets and leukocytes as both can influence the biologic
      effects of PRP. CLINICAL RELEVANCE: Depending on the clinical application,
      preparations of PRP should be considered based on their ability to concentrate
      platelets and leukocytes with sensitivity to pathologic conditions that will
      benefit most from increased platelet or reduced leukocyte concentration.

PMID- 21846926
TI  - Demographics and microbiology of otorrhea through patent tubes failing ototopical
      and/or oral antibiotic therapy.
AB  - OBJECTIVES: Posttympanostomy tube otorrhea (PTTO) results in significant health
      care cost and decreased satisfaction with care. The authors reviewed PTTO failing
      initial ototopical and/or oral antibiotic therapy and microbiology/susceptibility
      data from cultures. STUDY DESIGN: Case series with chart review. SETTING: A
      community university satellite ambulatory clinic and the outpatient clinic of a
      children's hospital. METHODS: Review of 202 patients with 228 discrete episodes
      of culture-positive otorrhea from January 2004 to January 2009. RESULTS: PTTO
      occurred an average of 13 months after tube placement. Median otorrhea duration
      was 21 days (mean, 42 days). A mean of 1.6 visits (range, 1-6) to the pediatric
      otolaryngology office was required for PTTO resolution. Ototopical therapy was
      reported used in 198 of 228 (87%) episodes of otorrhea prior to pediatric
      otolaryngology visit. Nearly 50% of patients were prescribed at least 1 or more
      courses of systemic antibiotics. Staphylococcus aureus accounted for 52% of the
      organisms cultured, with 57% methicillin-resistant S aureus (MRSA). S aureus
      resistance to clindamycin was high (49%) and resistance to levofloxacin was low
      (1.8%). MRSA was 68% clindamycin resistant, much higher than both ours and the
      children's hospital's clindamycin resistance rate of MRSA cultured from all other
      body sites. CONCLUSIONS: PTTO that presents as having failed ototopical and/or
      oral antibiotics most commonly consists of S aureus, Streptococcus pneumoniae,
      and Pseudomonas aeruginosa. MRSA is highly prevalent in this population. It is
      not necessary to culture PTTO that presents to an otolaryngology office, as
      resistance to levofloxacin was only 1.8%. It is unclear why the same
      fluoroquinolone ototopical therapy that failed initially is often successful in
      treating PTTO after otolaryngologist visit.

PMID- 21846927
TI  - Oxymetazoline ototoxicity in a chinchilla animal model.
AB  - OBJECTIVE: To investigate possible ototoxic effects of a one-time application of
      oxymetazoline drops in a chinchilla animal model with tympanostomy tubes. Study
      Design. A prospective, controlled animal study. SETTING: The Research Institute
      of the Montreal's Children Hospital, McGill University Health Centre. SUBJECTS
      AND METHODS: Ventilation tubes were inserted in both ears of 12 animals. One ear
      was randomly assigned to receive oxymetazoline drops (0.5 mL). The contralateral
      ear did not receive any drops, serving as a control ear. OUTCOME MEASURES:
      Distortion product otoacoustic emissions were measured bilaterally for a wide
      range of frequencies (between 1 and 16 kHz) before and 1 day after the
      application of oxymetazoline in the experimental ears. Two months later, the
      animals were sacrificed and all cochleae were dissected out and processed for
      scanning electron microscopy. RESULTS: In this established chinchilla animal
      model, the measured distortion product otoacoustic emission amplitudes and the
      morphological appearance on scanning electron microscopy were similar for both
      control and experimental ears. CONCLUSION: Oxymetazoline did not cause
      ototoxicity in a chinchilla animal model 2 months after a single application via
      a tympanostomy tube.

PMID- 21846928
TI  - Use of 2-octylcyanoacrylate (Dermabond) tissue adhesive for tip graft fixation in
      open rhinoplasty.
AB  - OBJECTIVES: To describe the use of 2-octylcyanoacrylate (2-OCA; Dermabond) for
      fixation of cartilage grafts in nasal tip surgery via an external approach in
      Asian patients. STUDY DESIGN: Case series with chart review. SETTING: Academic
      tertiary care medical center. SUBJECTS AND METHODS: This retrospective study
      analyzed data from 33 Korean patients who underwent open rhinoplasty using 2-OCA
      tissue adhesive for fixation of cartilage grafts in tip surgery. Autologous
      septal, conchal, costal, or homologous costal cartilage was used as graft
      materials. Layers of cartilages were bonded using 2-OCA tissue adhesive, and care
      was taken to prevent the tissue adhesive from spilling and directly contacting
      surrounding soft tissues. Preoperative and postoperative photographs were
      reviewed for objective and subjective assessment of aesthetic outcomes. RESULTS:
      Postoperative aesthetic outcomes were graded as excellent in 51.5%, fair in
      33.3%, and no change/worse in 15.2% of patients. Preoperative and postoperative
      anthropometric measurements showed that the nasal tip projection increased (0.53
      +/- 0.03 vs 0.57 +/- 0.05; P < .05) and the nasolabial angle improved (92.54 +/-
      6.95 vs 96.12 +/- 5.20; P < .05). The overall complication rate was 24.2%, and
      complications included erythema (9.1%), infection (12.1%), and aesthetic
      dissatisfaction (3.0%). CONCLUSION: Although using 2-OCA tissue adhesive for tip
      surgery simplifies the surgical procedures of fixating graft materials, the
      relatively high complication rate may preclude its use in nasal tip surgery via
      an external approach for Asian noses.

PMID- 21846929
TI  - Influence of intranasal epinephrine and lidocaine spray on olfactory function
      tests in healthy human subjects.
AB  - OBJECTIVE: Although topical decongestants and anesthetics are widely used in
      preparation for nasal endoscopy, no controlled trials have evaluated the effects
      of these agents on olfaction. STUDY DESIGN: Randomized double-blinded controlled
      trial. SETTING: Tertiary referral hospital. MATERIALS AND METHODS: The authors
      recruited 72 healthy subjects and randomly assigned them to 1 of 4 groups
      (control, phenylephrine group, lidocaine group, and both agents). After baseline
      tests with the Korean version of Sniffin' Stick Test II (KVSS II), topical agents
      were applied to each nostril. Fifteen minutes later, repeat tests were carried
      out. Pre- and postspray results of the olfactory tests were compared, and the
      differences among groups were analyzed. RESULTS: The mean +/- SD prespray KVSS II
      score of the study group was 30.2 +/- 3.8, and there were no statistically
      significant differences among the study groups (P = .353). Mean +/- SD pre- and
      postspray KVSS II scores were 29.0 +/- 3.5 and 30.7 +/- 3.7 (P = .128) in the
      control group, 30.6 +/- 3.6 and 31.7 +/- 3.3 (P = .262) in the phenylephrine
      group, and 31.4 +/- 3.6 and 32.1 +/- 3.1 (P = .557) in the lidocaine group,
      respectively. In the phenylephrine and epinephrine spray group, the mean +/- SD
      pre- and postspray scores were 29.9 +/- 4.4 and 31.3 +/- 3.7 (P = .071),
      respectively. CONCLUSIONS: Neither topical intranasal phenylephrine nor lidocaine
      use affected the results of the olfactory test, even when the agents were used in
      combination.

PMID- 21846931
TI  - Welcome to cardboard country: how plain packaging could change the subjective
      experience of smoking.

PMID- 21846930
TI  - Cost-effectiveness of interventions to return employees to work following long
      term sickness absence due to musculoskeletal disorders.
AB  - BACKGROUND: Sickness absence costs the UK economy around L20 billion per year.
      This study aims to assess the cost-effectiveness of interventions to return
      employees with musculoskeletal disorders to work, one of the major causes of long
      term sickness absence, using a mathematical model. METHODS: A Markov model was
      developed to assess the cost-effectiveness of three interventions: a workplace
      intervention; a physical activity and education intervention and a physical
      activity, education and workplace visit intervention. Extensive sensitivity
      analyses were undertaken to assess the impact of uncertainties upon the model
      results. RESULTS: All interventions assessed are estimated to have a cost per
      quality-adjusted life year gained below L3000 compared with usual care within the
      UK from a National Health Service (NHS) or societal perspective. Moreover, any
      intervention which returns at least an additional 3% of employees to work and
      costs less than an additional L3000 per employee, is likely to be considered
      economically attractive compared with usual care, relative to other interventions
      routinely funded by the NHS. CONCLUSIONS: This is the first economic evaluation
      in this area which extrapolates data beyond trial follow-up and synthesizes
      evidence from numerous sources. This sort of modelling approach should be
      considered for informing other public health policy decisions.

PMID- 21846932
TI  - Mechanism of AMPA receptor activation by partial agonists: disulfide trapping of
      closed lobe conformations.
AB  - The mechanism by which agonist binding to an ionotropic glutamate receptor leads
      to channel opening is a central issue in molecular neurobiology. Partial agonists
      are useful tools for studying the activation mechanism because they produce full
      channel activation with lower probability than full agonists. Structural
      transitions that determine the efficacy of partial agonists can provide
      information on the trigger that begins the channel-opening process. The ligand
      binding domain of AMPA receptors is a bilobed structure, and the closure of the
      lobes is associated with channel activation. One possibility is that partial
      agonists sterically block full lobe closure but that partial degrees of closure
      trigger the channel with a lower probability. Alternatively, full lobe closure
      may be required for activation, and the stability of the fully closed state could
      determine efficacy with the fully closed state having a lower stability when
      bound to partial relative to full agonists. Disulfide-trapping experiments
      demonstrated that even extremely low efficacy ligands such as 6-cyano-7
      nitroquinoxaline-2,3-dione can produce a full lobe closure, presumably with low
      probability. The results are consistent the hypothesis that the efficacy is
      determined at least in part by the stability of the state in which the lobes are
      fully closed.

PMID- 21846934
TI  - Plastic scintillation dosimetry: comparison of three solutions for the Cerenkov
      challenge.
AB  - In scintillation dosimetry, a Cerenkov background signal is generated when a
      conventional fibre optic is exposed to radiation produced by a megavoltage linear
      accelerator. Three methods of measuring dose in the presence of Cerenkov
      background are compared. In the first method, a second background fibre is used
      to estimate the Cerenkov signal in the signal fibre. In the second method, a
      colour camera is used to measure the combined scintillation and Cerenkov light in
      two wavelength ranges and a mathematical process is used to extract the
      scintillation signal. In the third method, a hollow air core light guide is used
      to carry the scintillation signal through the primary radiation field. In this
      paper, the strengths and weaknesses of each dosimetry system are identified and
      recommendations for the optimum method for common clinical dosimetry situations
      are made.

PMID- 21846933
TI  - Structure, dynamics, lipid binding, and physiological relevance of the putative
      GTPase-binding domain of Dictyostelium formin C.
AB  - Dictyostelium Formin C (ForC) is involved in the regulation of local actin
      cytoskeleton reorganization (e.g. during cellular adhesion or migration). ForC
      contains formin homology 2 and 3 (FH2 and -3) domains and an N-terminal putative
      GTPase-binding domain (GBD) but lacks a canonical FH1 region. To better
      understand the role of the GBD, its structure, dynamics, lipid-binding
      properties, and cellular functions were analyzed by NMR and CD spectroscopy and
      by in vivo fluorescence microscopy. Moreover, the program CS-Rosetta was tested
      for the structure prediction based on chemical shift data only. The ForC GBD
      adopts an ubiquitin-like alpha/beta-roll fold with an unusually long loop between
      beta-strands 1 and 2. Based on the lipid-binding data, the presence of DPC
      micelles induces the formation of alpha-helical secondary structure and a
      rearrangement of the tertiary structure. Lipid-binding studies with a mutant
      protein and a peptide suggest that the beta1-beta2 loop is not relevant for these
      conformational changes. Whereas small amounts of negatively charged
      phosphoinositides (1,2-dioctanoyl-sn-glycero-3-(phosphoinositol 4,5-bisphosphate)
      and 1,2-dihexanoyl-sn-glycero-3-(phosphoinositol 3,4,5-trisphosphate)) lower the
      micelle concentration necessary to induce the observed spectral changes, other
      negatively charged phospholipids (1,2-dihexanoyl-sn-glycero-3-(phospho-L-serine)
      and 1,2-dihexanoyl-sn-glycero-3-phospho-(1'-rac-glycerol)) had no such effect.
      Interestingly, bicelles and micelles composed of diacylphosphocholines had no
      effect on the GBD structure. Our data suggest a model in which part of the large
      positively charged surface area of the GBD mediates localization to specific
      membrane patches, thereby regulating interactions with signaling proteins. Our
      cellular localization studies show that both the GBD and the FH3 domain are
      required for ForC targeting to cell-cell contacts and early phagocytic cups and
      macropinosomes.

PMID- 21846935
TI  - A practical approach to estimate the weighted CT dose index over an infinite
      integration length.
AB  - The CT scanner-displayed radiation dose information is based on CT dose index
      (CTDI) over an integration length of 100 mm (CTDI(100)), which is lower than the
      CTDI over an infinite integration length (CTDI(infinity)). In an adult or a
      pediatric body CT scan, the limiting equilibrium dose can be established near the
      central scan plane, and CTDI(infinity) more closely indicates the accumulated
      dose than CTDI(100). The aim of this study was to (a) evaluate CTDI efficiencies,
      epsilon(CTDI(100)) = CTDI(100)/CTDI(infinity), for a multi-detector CT (MDCT)
      scanner, (b) examine the dependences of epsilon(CTDI(100)) on kV, beam width,
      phantom diameter, phantom length and position in phantom and (c) investigate how
      to estimate CTDI(infinity) based on the CT scanner-displayed information. We
      performed a comprehensive Geant4-based simulation study of a clinical CT scanner,
      and calculated epsilon(CTDI(100)) for a range of parameters. The results were
      compared with the epsilon(CTDI(100)) data of previous studies. Differences in the
      epsilon(CTDI(100)) values of these studies were assessed. A broad analysis of the
      epsilon(CTDI(100)) variations with the above-mentioned parameters was presented.
      Based on the results, we proposed a practical approach to obtain the weighted
      CTDI(infinity) using the CT scanner-displayed information. A reference
      combination of 120 kV and a beam width close to 20 mm can be selected to
      determine the efficiencies of the weighted CTDI by using either phantom
      measurements or computer simulations. The results can be applied to estimate the
      weighted CTDI(infinity) for 80-140 kV and the beam widths within 40 mm. Errors in
      the weighted CTDI(infinity) due to the variations of kV and beam width can be 5%
      or less for the MDCT scanners.

PMID- 21846936
TI  - Development and validation of a hybrid simulation technique for cone beam CT:
      application to an oral imaging system.
AB  - This paper proposes a hybrid technique to simulate the complete chain of an oral
      cone beam computed tomography (CBCT) system for the study of both radiation dose
      and image quality. The model was developed around a 3D Accuitomo 170 unit (J
      Morita, Japan) with a tube potential range of 60-90 kV. The Monte Carlo technique
      was adopted to simulate the x-ray generation, filtration and collimation. Exact
      dimensions of the bow-tie filter were estimated iteratively using experimentally
      acquired flood images. Non-flat radiation fields for different exposure settings
      were mediated via 'phase spaces'. Primary projection images were obtained by ray
      tracing at discrete energies and were fused according to the two-dimensional
      energy modulation templates derived from the phase space. Coarse Monte Carlo
      simulations were performed for scatter projections and the resulting noisy images
      were smoothed by Richardson-Lucy fitting. Resolution and noise characteristics of
      the flat panel detector were included using the measured modulation transfer
      function (MTF) and the noise power spectrum (NPS), respectively. The Monte Carlo
      dose calculation was calibrated in terms of kerma free-in-air about the
      isocenter, using an ionization chamber, and was subsequently validated by
      comparison against the measured air kerma in water at various positions of a
      cylindrical water phantom. The resulting dose discrepancies were found <10% for
      most cases. Intensity profiles of the experimentally acquired and simulated
      projection images of the water phantom showed comparable fractional increase over
      the common area as changing from a small to a large field of view, suggesting
      that the scatter was accurately accounted. Image validation was conducted using
      two small phantoms and the built-in quality assurance protocol of the system. The
      reconstructed simulated images showed high resemblance on contrast resolution,
      noise appearance and artifact pattern in comparison to experimentally acquired
      images, with <5% difference for voxel values of the aluminum and air insert
      regions and <3% difference for voxel uniformity across the homogeneous PMMA
      region. The detector simulation by use of the MTF and NPS data exhibited a big
      influence on noise and the sharpness of the resulting images. The hybrid
      simulation technique is flexible and has wide applicability to CBCT systems.

PMID- 21846937
TI  - Multi-observation PET image analysis for patient follow-up quantitation and
      therapy assessment.
AB  - In positron emission tomography (PET) imaging, an early therapeutic response is
      usually characterized by variations of semi-quantitative parameters restricted to
      maximum SUV measured in PET scans during the treatment. Such measurements do not
      reflect overall tumor volume and radiotracer uptake variations. The proposed
      approach is based on multi-observation image analysis for merging several PET
      acquisitions to assess tumor metabolic volume and uptake variations. The fusion
      algorithm is based on iterative estimation using a stochastic expectation
      maximization (SEM) algorithm. The proposed method was applied to simulated and
      clinical follow-up PET images. We compared the multi-observation fusion
      performance to threshold-based methods, proposed for the assessment of the
      therapeutic response based on functional volumes. On simulated datasets the
      adaptive threshold applied independently on both images led to higher errors than
      the ASEM fusion and on clinical datasets it failed to provide coherent
      measurements for four patients out of seven due to aberrant delineations. The
      ASEM method demonstrated improved and more robust estimation of the evaluation
      leading to more pertinent measurements. Future work will consist in extending the
      methodology and applying it to clinical multi-tracer datasets in order to
      evaluate its potential impact on the biological tumor volume definition for
      radiotherapy applications.

PMID- 21846938
TI  - Temperature dependences of piezoelectric, elastic and dielectric constants of L
      alanine crystal.
AB  - Temperature changes in the components of piezoelectric, elastic and dielectric
      tensors were studied in L-alanine crystals in the range 100-300 K. A jumpwise
      increase in the c(55) component of the elastic stiffness accompanied by maxima in
      damping of all face-shear modes observed at 199 K in L-alanine crystal were
      interpreted as a result of changes in the NH(3)(+) vibrations occurring through
      electron-phonon coupling. All components of the piezoelectric tensor show small
      anomalies in this temperature range. The components of the electromechanical
      coupling coefficient determined indicate that L-alanine is a weak piezoelectric.

PMID- 21846939
TI  - Charge transport in ultrathin iron-phthalocyanine thin films under high electric
      fields.
AB  - The temperature dependent current-voltage (J-V) characteristics of 20 nm thick
      iron-phthalocyanine films are investigated in the temperature range of 300-30 K,
      and in the bias range of +/-200 V. In the temperature range of 300-100 K, the
      charge transport is governed by bulk-limited processes with a bias dependent
      crossover from Ohmic (J~V) to exponentially distributed shallow trap mediated
      space-charge-limited conduction (J~V(alpha), alpha >= 2) to space-charge-limited
      conduction with field enhanced mobility (lnMU~E(1/2)). However, at temperatures
      less than 100 K, the charge transport is electrode-limited, and undergoes a bias
      dependent transition from Schottky (lnJ~V(1/2)) to multistep tunneling. From
      shallow trap mediated space-charge-limited conduction data the estimated room
      temperature mobility was found to be ~1.9 cm(2) V (-1) s(-1). The high mobility
      of films is attributed to better structural organization due to the face-on
      stacking of molecules, which is supported by x-ray diffraction and UV-visible
      spectroscopy data.

PMID- 21846940
TI  - Surface defects and temperature on atomic friction.
AB  - We present a theoretical study of the effect of surface defects on atomic
      friction in the stick-slip dynamical regime of a minimalistic model. We focus on
      how the presence of defects and temperature change the average properties of the
      system. We have identified two main mechanisms which modify the mean friction
      force of the system when defects are considered. As expected, defects change the
      potential profile locally and thus affect the friction force. But the presence of
      defects also changes the probability distribution function of the tip slip length
      and thus the mean friction force. We corroborated both effects for different
      values of temperature, external load, dragging velocity and damping. We also show
      a comparison of the effects of surface defects and surface disorder on the
      dynamics of the system.

PMID- 21846941
TI  - The effect of prolonged irradiation on defect production and ordering in Fe-Cr
      and Fe-Ni alloys.
AB  - The understanding of the primary radiation damage in Fe-based alloys is of
      interest for the use of advanced steels in future fusion and fission reactors. In
      this work Fe-Cr alloys (with 5, 6.25, 10 and 15% Cr content) and Fe-Ni alloys
      (with 10, 40, 50 and 75% Ni content) were used as model materials for studying
      the features of steels from a radiation damage perspective. The effect of
      prolonged irradiation (neglecting diffusion), i.e. the overlapping of single 5
      keV displacement cascade events, was studied by molecular dynamics simulation. Up
      to 200 single cascades were simulated, randomly induced in sequence in one
      simulation cell, to study the difference between fcc and bcc lattices, as well as
      initially ordered and random crystals. With increasing numbers of cascades we
      observed a saturation of Frenkel pairs in the bcc alloys. In fcc Fe-Ni, in
      contrast, we saw a continuous accumulation of defects: the growth of stacking
      fault tetrahedra and a larger number of self-interstitial atom clusters were seen
      in contrast to bcc alloys. For all simulations the defect clusters and the short
      range order parameter were analysed in detail depending on the number of cascades
      in the crystal. We also report the modification of the repulsive part of the Fe
      Ni interaction potential, which was needed to study the non-equilibrium
      processes.

PMID- 21846942
TI  - Altered transcription and expression of PTEN in breast tumors: is it regulated by
      hypermethylation?
AB  - Breast cancer (BC) is the commonest cancer in women worldwide with a widely
      variable incidence between countries and regions. BC is either familial or
      sporadic. Mutations in tumor suppressor gene, PTEN has been associated with
      syndromic BC and in a subset of sporadic BCs. The present study was carried out
      in archival formalin fixed paraffin embedded samples. Immunohistochemistry and
      quantitative RTPCR indicated a reduced expression/ transcription of PTEN in tumor
      as compared to adjacent non-tumorous tissue. However, the promoter methylation
      evaluated by Methylation Specific Restriction Assay indicated that only 20% of
      the tumors showed PTEN methylation and could not account for the rest of the
      samples with reduced expression. Overall evidence from literature and our present
      findings indicate that: (i) Loss of Heterozygosity at PTEN gene locus (ii)
      germline and somatic gene mutations of PTEN (iii) epigenetic silencing by
      methylation in PTEN promoter CpG cluster (iv)protein interactions which reduce
      PTEN transcription and (v) PTEN protein degradation together play an important
      role in the etiology of BC.

PMID- 21846943
TI  - Putative roles of circulating resistin in patients with asthma, COPD and
      cigarette smokers.
AB  - AIMS: To investigate the hypothesis that circulating resistin reflects the degree
      of pulmonary inflammation, this study explores putative roles of resistin in
      patients with acute and stable inflammatory obstructive airway diseases and
      cigarette smokers. METHODS: We determined complements C3, C4, fasting resistin,
      insulin, glucose and lipid profile; calculated insulin resistance (homeostasis
      model assessment (HOMA-IR) in patients with acute asthma exacerbation (n=34);
      stable asthma (n=26) and stable chronic obstructive pulmonary disease (COPD;
      n=26), cigarette smokers (n=81), and healthy control subjects (n=42). We
      determined the associations between these variables and pulmonary function tests.
      RESULTS: Patients with COPD, acute and stable asthma had significantly higher
      resistin and insulin than control subjects. Resistin, insulin, HOMA-IR, FEV1% and
      FEV1/FVC were significantly (p< 0.05) different between patients with acute
      asthma compared with stable asthma and COPD; smokers had similar levels of
      resistin, C3 and C4 as patients with asthma and COPD. In smokers, patients with
      asthma or COPD, resistin showed significant inverse correlations with FEV1%;
      FEV1/FVC% and positive significant correlations with BMI and HOMA-IR. Logistic
      regression showed that resistin is associated (p< 0.05) with inflammatory
      obstructive airways disease - odds ratio (OR)=1.22 and smoking OR=1.18.
      CONCLUSION: Resistin may be a disease activity marker and may contribute to
      insulin resistance in smokers, asthma and COPD.

PMID- 21846944
TI  - NF-kB expression in IgA nephropathy outcome.
AB  - Some studies have demonstrated the involvement of nuclear factor-kappa B (NF-kB)
      in the pathogenesis of glomerulonephritis. The aim of our study was twofold: (1)
      to analyze the prognostic value of NF-kB expression in primary IgA nephropathy
      (IgAN) and (2) to compare the results of NF-kB expression by immunohistochemistry
      (IHC) and southwestern histochemistry (SWH). We analyzed 62 patients diagnosed
      with IgAN from 1987 to 2003. We used monoclonal antibodies to CD68 and mast cell
      tryptase and polyclonal antibodies to TGF-beta1, alpha-SMA and NF-kB p65. We used
      SWH for the in situ detection of activated NF-kB. The results showed that NF-kB
      expression (mainly by SWH) correlated with clinical and histological parameters.
      An unfavorable clinical course of IgAN was significantly related to tubular NF-kB
      expression by SWH, but not by IHC. The Kaplan-Meier curves demonstrated that
      increased NF-kB expression, which was measured by IHC and SWH, decreased renal
      survival. In conclusion, the increased expression of NF-kB in the tubular area
      may be a predictive factor for the poor prognosis of patients with IgAN. Compared
      with IHC, NF-kB expression determined by SWH was correlated with a larger number
      of parameters of poor disease outcome.

PMID- 21846945
TI  - Association of interleukin 23 receptor gene with sarcoidosis.
AB  - Interleukin 23 receptor (IL23R) gene has been reported as a genetic factor
      strongly associated with inflammatory bowel disease, psoriasis, and ankylosing
      spondylitis. We investigated the association between IL23R gene single nucleotide
      polymorphisms (SNPs) and susceptibility to sarcoidosis, including the clinical
      manifestation of uveitis. Ninety-one sarcoidosis subjects (58 with and 33 without
      uveitis) and 104 healthy controls were genotyped for eleven IL23R SNPs. DNA was
      amplified using specific PCR primers and genotyped by denaturing HPLC and/or
      direct DNA sequencing. Case-control frequency comparisons were analyzed using Chi
      square test. Three IL23R SNPs, rs7517847 (intron 6), rs11465804 (intron 8), and
      rs11209026 (exon 9, c.1142G>A, p.Arg381Gln) were associated with sarcoidosis in
      our population (p<0.05): rs7517847 showed increased frequencies in sarcoidosis
      compared to controls, but rs11465804 and rs11209026 were decreased. Two of these
      SNPs were associated with the uveitis subgroup compared to controls: rs11465804
      (0.9% vs. 7.2%, OR=0.11, P=0.013) and rs11209026 (1.8% vs. 7.3%, OR=0.23,
      P=0.038). This finding indicates the association of IL23R polymorphism with
      sarcoidosis, especially with sarcoid uveitis. IL23R may be a common
      susceptibility gene shared by several autoimmune disorders including inflammatory
      bowel disease, psoriasis, and ankylosing spondylitis and sarcoid uveitis.

PMID- 21846946
TI  - Gene expression changes in femoral head necrosis of human bone tissue.
AB  - Osteonecrosis of the femoral head (ONFH) is the result of an interruption of the
      local circulation and the injury of vascular supply of bone. Multiple factors
      have been implicated in the development of the disease. However the mechanism of
      ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our
      investigation was to identify genes that are differently expressed in ONFH vs.
      non-ONFH human bone and to describe the relationships between these genes using
      multivariate data analysis. Six bone tissue samples from ONFH male patients and 8
      bone tissue samples from non-ONFH men were examined. The expression differences
      of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time
      RT-PCR system. The significance test indicated marked differences in the
      expression of nine genes between ONFH and non-ONFH individuals. These altered
      genes code for collagen molecules, an extracellular matrix digesting
      metalloproteinase, a transcription factor, an adhesion molecule, and a growth
      factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone
      tissues can be distinguished by the multiple expression profile analysis of
      numerous genes controlled via canonical TGFB pathway as well as genes coding for
      extracellular matrix composing collagen type molecules. The markedly altered gene
      expression profile observed in the ONFH of human bone tissue may provide further
      insight into the pathogenetic process of osteonecrotic degeneration of bone.

PMID- 21846947
TI  - Relationship between toll-like receptor 8 gene polymorphisms and pediatric
      pulmonary tuberculosis.
AB  - OBJECTIVES: Genetic variants in Toll-like receptors (TLRs) are considered a
      potential indicator for host susceptibility to and outcome of several infectious
      diseases including tuberculosis. The aim of this study was to determine whether 
      129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric
      pulmonary tuberculosis in Turkish population. METHODS: The -129 C/G and Met1Val
      polymorphisms were studied in 124 children with pulmonary tuberculosis compared
      to 150 age-matched healthy control subjects. RESULTS: We did not identify any
      statistically significant differences between the patients with TB and control
      groups with regard to the frequency of genotypes GG or G/(-), CG, and CC or C/(
      ); and alleles G and C at rs3764879 (p> 0.05). We found a strong association with
      genotype A/(-) at rs3764880 with susceptibility to pulmonary TB in males (OR
      2.87, 95%CI 1.38-5.98, p=0.007). CONCLUSIONS: Our results provide evidence, for
      the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in
      male children. Additional research to verify our results are necessary.
      Tuberculosis in children presents particularly difficult challenges, but research
      priorities and advances in pediatric tuberculosis could provide wider insights
      and opportunities for tuberculosis control.

PMID- 21846948
TI  - Associations of -308G/A polymorphism of tumor necrosis factor (TNF)-alpha gene
      and serum TNF-alpha levels with measures of obesity, intra-abdominal and
      subcutaneous abdominal fat, subclinical inflammation and insulin resistance in
      Asian Indians in north India.
AB  - OBJECTIVES: Obesity is associated with high levels proinflammatory cytokines like
      tumour necrosis factor alpha (TNF-alpha), which may play an important role in the
      genesis of insulin resistance. We evaluated the relationship of -308G/A
      polymorphism of TNF-alpha gene with obesity and insulin resistance in Asian
      Indians in north India. METHODS: This cross-sectional study included 151
      apparently healthy individuals (79 males, 72 females) 18-50 yrs of age from New
      Delhi, India. Body composition by dual-energy x-ray absorptiometry (DEXA) and
      abdominal fat by magnetic resonance imaging (MRI) were measured. Biochemical
      measurements included OGTT, lipids, fasting insulin, hs-CRP and TNF-alpha levels.
      We analysed -308G/A polymorphism of TNF-alpha gene and studied its association
      with obesity and biochemical parameters. RESULTS: At comparable BMI, abdominal
      obesity was more prevalent in females (50%) as compared to males (20%). The wild
      genotype (GG) was present in 78.8%, GA in 17.9%, and AA in 3.3% subjects.
      Measures of body composition, abdominal fat distribution, lipids, insulin, hs-CRP
      and TNF-alpha levels were not influenced by the presence of -308G/A polymorphism.
      Serum TNF-alpha levels correlated significantly with fasting insulin in both
      genders. CONCLUSION: TNF-alpha levels correlate with fasting insulin but not with
      indicators of body composition in Asian Indians. The -308G/A polymorphism of TNF
      alpha gene is not associated with differences in the serum levels of TNF-alpha in
      Asian Indians.

PMID- 21846949
TI  - Immunological functions of oxidized human immunoglobulin G in type 1diabetes
      mellitus: its potential role in diabetic smokers as a biomarker of elevated
      oxidative stress.
AB  - The role of oxidized immunoglobulin G in type 1 diabetic smokers has been
      investigated in the present study. Human immunoglobulin G (IgG) was modified by
      reactive oxygen species (ROS). The binding characteristics of circulating
      autoantibodies in type 1 diabetes patients against native and modified IgG were
      assessed by direct binding ELISA. High degree of specific binding by 68.5% of
      patients sera towards ROS-modified IgG was observed in comparison to its native
      analogue (p< 0.05). In addition, diabetic smokers (n=28) were examined and the
      results were compared with diabetic non-smokers (n=26). Circulating antibodies of
      diabetic smokers showed substantially stronger binding to modified IgG as
      compared with the antibodies present in diabetic non-smokers (p< 0.05). Normal
      human sera (n=53) showed negligible binding with either antigen. Competitive
      inhibition ELISA reiterates the direct binding results. The increase in total
      serum protein carbonyl levels in the diabetic smokers was largely due to an
      increase in oxidized IgG. Diabetic smokers showed substantially higher carbonyl
      contents in sera as well as in purified IgG as compared with sera and IgG of
      diabetic non-smokers. Collectively, the oxidation of plasma proteins, especially
      IgG, might enhance oxidative stress in type 1 diabetes smokers.

PMID- 21846950
TI  - Pharmacological enhancement of glutamate transport reduces excitotoxicity in
      vitro.
AB  - PURPOSE: Glutamate transporters are responsible for removing glutamate from the
      extracellular space and have the potential to protect neurons from
      excitotoxicity. In the present study, the effects of ceftriaxone and (2R, 4R)
      APDC (APDC) on the protein expression of GLAST and GLT-1, the rate of glutamate
      uptake, and neuroprotection were evaluated in a cell culture model of glutamate
      excitotoxicity. METHODS: Mixed neuron/astrocyte cultures were prepared from 1 day
      old rat pups. Protein levels of GLAST and GLT-1 glutamate transporters were
      quantified using In-Cell Western techniques after acute or 5-day treatment with
      either ceftriaxone or APDC. Glutamate uptake was measured using Michaelis-Menten
      kinetics to evaluate the effects of 5-day treatment with ceftriaxone or APDC.
      Neuronal cell death in response to a 10-minute 1 mM glutamate challenge was
      measured following 5-day treatment with either ceftriaxone or APDC. RESULTS: Five
      day treatment with 100 MUM ceftriaxone significantly increased both GLAST and GLT
      1 protein levels 31.3% and 47.5% above control, respectively, increased the Vmax
      29.3%, increased the Km of glutamate uptake 117.9%, and reduced neuronal death
      22.0% after a 1 mM glutamate challenge. Five-day treatment with 1 mM APDC
      significantly increased GLAST protein levels 27.6%, increased the Vmax 92.4%,
      increased the Km of glutamate transport 118.9%, and decreased neuronal death
      36.8% after a 1 mM glutamate challenge. CONCLUSIONS: Chronic treatment with
      ceftriaxone or APDC provided neuroprotection from glutamate excitotoxicity while
      increasing GLAST and GLT-1 protein levels and increasing glutamate uptake. These
      compounds may have therapeutic potential in chronic excitotoxic neurodegenerative
      diseases.

PMID- 21846951
TI  - Changes of amino acid concentrations in the rat vestibular nuclei after midline
      lesions.
AB  - Changes in concentrations of amino acids, especially GABA, glutamate, and
      aspartate, occur in vestibular nuclei after removal of cerebellar and labyrinth
      inputs. Here, we examined the effects of transecting midline-crossing connections
      between the two vestibular nuclear complexes, which especially include
      commissural connections. Three rats were euthanized at each of 2, 7, and 30 days
      after a midline cut at the level of the vestibular nuclei. Two sham-lesioned rats
      were prepared for surgery but no cut made. Samples of superior (SuVN), dorsal and
      ventral lateral (LVNd and LVNv), dorsal and ventral medial (MVNd and MVNv), and
      spinal vestibular nuclei (SpVN) were microdissected from freeze-dried coronal
      sections and assayed for amino acid concentrations. Reductions of GABA
      concentration occurred by 2 days and continued through 30 days after surgery in
      most regions. Glutamate and aspartate concentrations decreased by 2 days in LVN
      and MVN, then glutamate showed some recovery by 30 days. Glutamine and taurine
      concentrations increased in almost all regions. Glycine concentration decreased
      in MVN and LVNv. Our results support association of GABA, glutamate, aspartate,
      and to some extent glycine, with vestibular crossed connections. Comparisons to
      our previous studies suggest some complex lesion effects, especially in LVNd.

PMID- 21846953
TI  - Motion sickness: a cholinomimetic agent hypothesis.
AB  - Motion sickness has been defined as a set of physiological signs and symptoms
      produced as a result of prolonged sensory conflict in central nervous system
      vestibular centers. It has long been noted that the particular pattern of motion
      sickness signs and symptoms does not fit the conventional "fight or flight vs.
      rest and digest" autonomic synergy. We argue that most of the progression of
      symptoms is consistent with a new etiologic hypothesis: that an as-yet
      unidentified ganglionic cholinomimetic agent is slowly released in proportion to
      sensory conflict. The agent accumulates systemically and stimulates the
      peripheral sympathetic and parasympathetic ganglia, the adrenal medulla, and
      potentiates the response of central cholinergic emetic pathways to the same
      conflict stimulus. The predominant effects of ganglionic stimulation on each
      autonomic organ, determined by resting tone, are selectively enhanced or
      inhibited by adrenal catecholamine release, producing the atypical pattern of
      autonomic changes seen in motion sickness. The adrenergic response may eventually
      also counter the central emetic drive. The hypothesis could be experimentally
      pursued via human and animal experiments employing a nicotinic antagonist that
      has both central and peripheral ganglionic actions such as mecamylamine.

PMID- 21846952
TI  - Differences between perception and eye movements during complex motions.
AB  - During passive whole-body motion in the dark, the motion perceived by subjects
      may or may not be veridical. Either way, reflexive eye movements are typically
      compensatory for the perceived motion. However, studies are discovering that for
      certain motions, the perceived motion and eye movements are incompatible. The
      incompatibility has not been explained by basic differences in gain or time
      constants of decay. This paper uses three-dimensional modeling to investigate
      gondola centrifugation (with a tilting carriage) and off-vertical axis rotation.
      The first goal was to determine whether known differences between perceived
      motions and eye movements are true differences when all three-dimensional
      combinations of angular and linear components are considered. The second goal was
      to identify the likely areas of processing in which perceived motions match or
      differ from eye movements, whether in angular components, linear components
      and/or dynamics. The results were that perceived motions are more compatible with
      eye movements in three dimensions than the one-dimensional components indicate,
      and that they differ more in their linear than their angular components. In
      addition, while eye movements are consistent with linear filtering processes,
      perceived motion has dynamics that cannot be explained by basic differences in
      time constants, filtering, or standard GIF-resolution processes.

PMID- 21846954
TI  - Optokinetic response in patients with vestibular areflexia.
AB  - Optokinetic nystagmus (OKN) responses (stimuli 40 degrees /s and 60 degrees /s)
      were evaluated in 121 patients with vestibular areflexia (VA) and were compared
      with a control group of 99 control subjects matched by age. The mean response
      levels were significantly higher in the VA group than in the control group: 1.7
      degrees /s at 40 degrees /s stimulation, and 4.4 degrees /s at 60 degrees /s. The
      VA group showed a significantly wider scattering and greater variances and, as a
      group, they exhibited higher OKN gains than the control subjects. We suggest that
      the higher gain of OKN responses in VA patients can be attributed to an increased
      efficiency in signal processing by the cortical optokinetic system. This
      enhancement may be similar to the enhancement which, in healthy subjects, is
      produced by "optokinetic training".

PMID- 21846955
TI  - The 2D modified head impulse test: a 2D technique for measuring function in all
      six semi-circular canals.
AB  - The head impulse test can be used to measure peripheral vestibular function of
      all six semicircular canals. Traditionally, vertical canal function is measured
      by rotating the head from a starting neutral position (forward facing) about a
      diagonal plane that bisects the sagittal and coronal planes. These types of head
      rotations elicit eye movements with large vertical and torsional (about the line
      of sight) angular velocity components. Three-dimensional (3D: horizontal,
      vertical and torsional) eye measurement techniques are needed to measure these
      velocity components. We wanted to determine whether 2D measurements coupled to a
      modified head impulse test are sufficient to measure function of all six canals.
      In this study we measured individual canal function in patients (n=5) with
      peripheral unilateral hypofunction and control subjects (n=4) using the
      traditional head impulse test and the 'gold standard' 3D (dual-coil) scleral
      search coil technique. We compared these results with those from our 2D modified
      head impulse test using the 2D coil technique (single-coil). We show that both
      techniques detect similar levels of asymmetrical function in patients and are
      equally accurate in isolating canals with hypofunction. We conclude that 2D eye
      measurement techniques, such as video pupil-tracking, can be used to test all six
      canals.

PMID- 21846956
TI  - Visual analog scale to assess vertigo and dizziness after repositioning maneuvers
      for benign paroxysmal positional vertigo.
AB  - INTRODUCTION: The aim of this study was to evaluate the value of Visual Analog
      Scale (VAS) in evaluating vertigo and dizziness in patients with benign
      paroxysmal positional vertigo (BPPV). MATERIALS AND METHODS: 226 adult patients
      suffering from a BPPV and undergoing repositioning maneuvers were included in
      this prospective study. Vertigo (V) and dizziness (D) were separately evaluated
      from day 0 to 5 by VAS. V and D scores decreased both exponentially but with
      different constants. D scores were not correlated to V suggesting the
      independency of the ratings. D was related to the dizziness intensity level
      expressed at interrogation. Both D and V scores were related to patients' global
      satisfaction. CONCLUSION: VAS allows differentiating vertigo from dizziness and
      provides coherent results with other clinical indicators.

PMID- 21846957
TI  - The total face mask is more comfortable than the oronasal mask in noninvasive
      ventilation but is not associated with improved outcome.
AB  - BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) is commonly used to
      improve ventilation and oxygenation and avoid endotracheal intubation and
      mechanical ventilation. Although clinically indicated, most patients fail to use
      NPPV due to mask intolerance. A total face mask was designed to increase
      compliance, but whether this translates into better outcome (improvement in
      clinical and blood gas parameters and less intubation) is unknown. OBJECTIVES: We
      compared the evolution of the clinical parameters, blood gases, levels of
      ventilatory support and rate of endotracheal intubation using the total face mask
      or the traditional oronasal mask during NPPV. METHODS: A total of 60 patients
      were randomized to use either mask during NPPV. The clinical and laboratory
      parameters, as well as the level of ventilatory support were recorded at
      different intervals in both groups for up to 6 h. In addition, the tolerance for
      each mask and the need for endotracheal intubation were compared. RESULTS:
      Patients tolerated the total face mask significantly better (p = 0.0010) and used
      NPPV for a longer time (p = 0.0017) when compared with the oronasal mask. Just 1
      patient switched to the total face mask because of intolerance. Although better
      tolerated, the rate of endotracheal intubation was similar in both groups (p =
      0.4376), as was the clinical and laboratory evolution. CONCLUSIONS: The total
      face mask was more comfortable, allowing the patients to tolerate NPPV longer;
      however, these accomplishments did not translate into a better outcome. Due to
      its comfort, the total face mask should be available, at least as an option, in
      units where NPPVs are routinely applied.

PMID- 21846959
TI  - Is the distance enough to eradicate in situ or early invasive subungual melanoma
      by wide local excision? from the point of view of matrix-to-bone distance for
      safe inferior surgical margin in Koreans.

PMID- 21846958
TI  - Xanthine oxidase inhibition attenuates endothelial dysfunction caused by chronic
      intermittent hypoxia in rats.
AB  - BACKGROUND: Xanthine oxidase is a major source of superoxide in the vascular
      endothelium. Previous work in humans demonstrated improved conduit artery
      function following xanthine oxidase inhibition in patients with obstructive sleep
      apnea. OBJECTIVES: To determine whether impairments in endothelium-dependent
      vasodilation produced by exposure to chronic intermittent hypoxia are prevented
      by in vivo treatment with allopurinol, a xanthine oxidase inhibitor. METHODS:
      Sprague-Dawley rats received allopurinol (65 mg/kg/day) or vehicle via oral
      gavage. Half of each group was exposed to intermittent hypoxia (FIO(2) = 0.10 for
      1 min, 15*/h, 12 h/day) and the other half to normoxia. After 14 days, gracilis
      arteries were isolated, cannulated with micropipettes, and perfused and
      superfused with physiological salt solution. Diameters were measured before and
      after exposure to acetylcholine (10(-6)M) and nitroprusside (10(-4)M). RESULTS:
      In vehicle-treated rats, intermittent hypoxia impaired acetylcholine-induced
      vasodilation compared to normoxia (+4 +/- 4 vs. +21 +/- 6 MUm, p = 0.01).
      Allopurinol attenuated this impairment (+26 +/- 6 vs. +34 +/- 9 MUm for
      intermittent hypoxia and normoxia groups treated with allopurinol, p = 0.55). In
      contrast, nitroprusside-induced vasodilation was similar in all rats (p = 0.43).
      Neither allopurinol nor intermittent hypoxia affected vessel morphometry or
      systemic markers of oxidative stress. Urinary uric acid concentrations were
      reduced in allopurinol- versus vehicle-treated rats (p = 0.02). CONCLUSIONS:
      These data confirm previous findings that exposure to intermittent hypoxia
      impairs endothelium-dependent vasodilation in skeletal muscle resistance arteries
      and extend them by demonstrating that this impairment can be prevented with
      allopurinol. Thus, xanthine oxidase appears to play a key role in mediating
      intermittent hypoxia-induced vascular dysfunction.

PMID- 21846960
TI  - Necrosis of ears after use of cocaine probably adulterated with levamisole.
AB  - BACKGROUND/AIMS: Levamisole is an anthelminthic drug with immunomodulatory
      properties that has been found to be an adulterant of cocaine in the last 2
      years. It was present at least in 70% of tainted cocaine in the U.S.A. in 2009.
      METHODS: We present the case of a 40-year-old patient with a history of weekend
      cocaine use who consulted for bilateral necrotic lesions in the ears that had
      appeared 3 days after the last use. RESULTS: Levamisole causes a typical clinical
      picture characterized by bilateral necrosis of the ears, positive perinuclear
      antineutrophil cytoplasmic antibodies and laboratory findings of antiphospholipid
      syndrome, such as anticardiolipin antibodies and/or lupus anticoagulant.
      CONCLUSION: Dermatologists should be aware of this new entity, which is likely to
      be more and more frequent due to the increasing use of cocaine. Here we describe
      a clinical case that is likely to be secondary to levamisole-tainted cocaine and
      review the literature.

PMID- 21846961
TI  - Effects of vitamin treatment or supplements with purported antioxidant properties
      on skin cancer prevention: a meta-analysis of randomized controlled trials.
AB  - AIMS: To investigate the effect of vitamin treatment or supplements with
      purported antioxidant properties on the primary and secondary prevention of skin
      cancer using a meta-analysis of randomized controlled trials (RCTs). METHODS: We
      searched PubMed, Embase and the Cochrane Library in June 2009. Among 398 articles
      searched, 11 articles on 10 RCTs were included in the final analysis. RESULTS: In
      a fixed-effects meta-analysis of all 10 trials, vitamin treatment or supplements
      with purported antioxidant properties were found to have no preventive effect on
      skin cancer [relative risk (RR) = 0.98; 95% confidence interval (CI) = 0.94
      1.03]. Similar findings were observed in a subgroup meta-analysis of 10 studies
      on both primary prevention trials (RR = 0.98; 95% CI = 0.93-1.03) and secondary
      prevention trials (RR = 0.97; 95% CI = 0.83-1.13). Further, subgroup meta
      analyses revealed no preventive effect on cancer by type of antioxidant, type of
      cancer and the methodological quality of the studies. CONCLUSION: The current
      meta-analysis of RCTs indicated that there is no clinical evidence to support an
      overall primary and secondary preventive effect of vitamin treatment or
      supplements with purported antioxidant properties on skin cancer. The effect of
      vitamin supplements on skin cancer should not be overemphasized.

PMID- 21846962
TI  - Early versus late pulmonary rehabilitation in chronic obstructive pulmonary
      disease patients with acute exacerbations: a randomized trial.
AB  - BACKGROUND: Around the world, the timing of referral of chronic obstructive
      pulmonary disease (COPD) patients for pulmonary rehabilitation differs from
      immediately after exacerbation (early) to later on when patients are in a stable
      state (late). There are no trials comparing the different time points of referral
      for pulmonary rehabilitation. OBJECTIVES: Our aim was to compare the effects of
      early and late pulmonary rehabilitation on exacerbation rates and health-related
      quality of life (HRQOL) in COPD patients with exacerbations. METHODS: We
      randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease
      stages II-IV) with a recent exacerbation to early (within 2 weeks) or late
      pulmonary rehabilitation (starting 6 months after randomization and in a stable
      state). The primary outcome was the exacerbation rate over 18 months, and
      secondary outcomes included HRQOL and mortality. We used multivariate analyses
      and an intention-to-treat analysis approach. RESULTS: We randomized 36 patients
      to pulmonary rehabilitation. On average, patients with early rehabilitation (n =
      19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or
      antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation
      (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43-1.63; p =
      0.60). Over the 18-month period, patients with late rehabilitation experienced
      more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74
      and on the Medical Research Council dyspnea scale 0.37), but neither these
      differences nor any difference in HRQOL domains reached statistical significance.
      CONCLUSIONS: We did not find any statistically significant differences between
      early and late pulmonary rehabilitation. However, our trial indicates that early
      rehabilitation may lead to faster recovery of HRQOL after exacerbations compared
      to rehabilitation later on when patients are in a stable state.

PMID- 21846963
TI  - Cutaneous and mucosal aphthosis during temsirolimus therapy for advanced renal
      cell carcinoma: review of cutaneous and mucosal side effects of mTOR inhibitors.
AB  - Temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is a new
      targeted therapy used in advanced renal cell carcinoma and mantle cell lymphoma
      and is currently tested in several other human tumors. It induces several
      cutaneous and mucosal side effects, including painful, dose-limiting stomatitis.
      We report the unusual case of a 77-year-old man who developed severe mucosal,
      scrotal and perianal cutaneous aphthous-like ulcerations, 6 weeks after
      introduction of temsirolimus therapy for advanced-stage renal cell carcinoma.
      Other causes of aphthous-like ulcerations were ruled out. Topical corticosteroids
      remained ineffective. It led to the interruption of the treatment. Introduction
      of colchicine resulted in a dramatic improvement within 1 month. Reintroduction
      of temsirolimus with concomitant colchicine therapy was followed by a delayed
      recurrence of the lesions. We provide here a review of the potential cutaneous
      and mucosal side effects of mTOR inhibitors.

PMID- 21846964
TI  - Growth hormone/IGF-I axis and growth hormone receptor mutations in idiopathic
      short stature.
AB  - BACKGROUND/AIMS: It was hypothesized that some children with idiopathic short
      stature (ISS) may have partial insensitivity to growth hormone (GH). In this
      study analysis of the GH/IGF-I axis as well as GH receptor (GHR) gene was done in
      children with ISS to determine the possible underlying factor(s) to their short
      stature. METHODS: Forty-eight patients with a diagnosis of ISS were studied; 33
      boys and 15 girls aged 13.6 +/- 3.7 years. Molecular analysis of the GHR was
      performed and GH sensitivity was tested by the IGF-I generation test. RESULTS:
      Basal IGF-I levels were <-2 SD in 22.9%, and 53.5% showed an IGF-I response below
      40% (0-38%) to GH stimulation. GH-binding protein (GHBP) levels were below the
      normative mean in almost all patients. Mutations in the region of the GHR gene
      that codes for the extracellular domain of the receptor were found in 15.5%; one
      newly described mutation was recorded. CONCLUSION: With the possible exception of
      the novel G62V mutation, functional studies of the other 2 heterozygous mutations
      found in 6 of our patients are needed in order to prove their impact on short
      stature.

PMID- 21846965
TI  - Comparative chromosome maps of neotropical rodents Necromys lasiurus and
      Thaptomys nigrita (Cricetidae) established by ZOO-FISH.
AB  - This work presents chromosome homology maps between Mus musculus (MMU) and 2
      South American rodent species from the Cricetidae group: Necromys lasiurus (NLA,
      2n = 34) and Thaptomys nigrita (TNI, 2n = 52), established by ZOO-FISH using
      mouse chromosome-specific painting probes. Extending previous molecular
      cytogenetic studies in Neotropical rodents, the purpose of this work was to
      delineate evolutionary chromosomal rearrangements in Cricetidae rodents and to
      reconstruct the phylogenetic relationships among the Akodontini species. Our
      phylogenetic reconstruction by maximum parsimony analysis of chromosomal
      characters confirmed one consistent clade of all Neotropical rodents studied so
      far. In both species analyzed here, we observed the syntenic association of
      chromosome segments homologous to MMU 8/13, suggesting that this chromosome form
      is a synapomorphic trait exclusive to Neotropical rodents. Further, the
      previously described Akodontini-specific syntenic associations MMU 3/18 and MMU
      6/12 were observed in N.lasiurus but not in T. nigrita, although the latter
      species is considered a member of the Akodontini tribe by some authors. Finally,
      and in agreement with this finding, N.lasiurus and Akodon serrensis share the
      derived fission of MMU 13, which places them as basal sister clades within
      Akodontini.

PMID- 21846967
TI  - Origins and breakpoint analyses of copy number variations: up close and personal.
AB  - Array-based methods have enabled the detection of many genomic gains and losses.
      These are stated as copy number variants (CNVs) and comprise up to 13% of the
      human genome. Based on their breakpoints and modes of formation CNVs are termed
      recurrent or nonrecurrent. Recurrent CNVs are flanked by low copy repeats and are
      of a fixed size. They arise as a result of misalignment during meiosis by a
      mechanism named nonallelic homologous recombination. Several of such recurrent
      CNVs have been linked to human diseases. Nonrecurrent CNVs, which are not flanked
      by low copy repeats, are of variable size and may arise via mechanisms like
      nonhomologous end joining and replication-based mechanisms described by the fork
      stalling and template switching and microhomology-mediated break-induced
      replication models. It is becoming clear that most disease-causing CNVs are
      nonrecurrent and generally arise via replication-based mechanisms. Furthermore,
      it is now appreciated that genomic features other than low copy repeats play a
      role in the formation of nonrecurrent CNVs. This review will discuss the
      different mechanisms of CNV formation and how high resolution analyses of CNV
      breakpoints have added to our knowledge of their precise structure.

PMID- 21846966
TI  - Frequent loss of the BLID gene in early-onset breast cancer.
AB  - The BH3-like motif-containing inducer of cell death (BLID) is an intronless gene
      localized on 11q24.1. Loss of that region has frequently been reported in early
      onset breast cancer and is significantly associated with poor prognosis and
      reduced survival. Downregulation of BLID is associated with younger age, triple
      negative phenotype, and reduced disease-free and overall survival of breast
      cancer patients. In this study, we investigated allelic loss of BLID in breast
      tumor specimens from 78 women with invasive breast cancer using 2 dinucleotide
      polymorphic markers closely linked to the BLID gene (no intragenic marker for
      BLID is available). Seventy-three cases were informative. Overall, loss of
      heterozygosity (LOH) at the BLID locus was detected in 32% of the informative
      cases (23/73). However, in patients 40 years old and younger, LOH was detected in
      50% of the cases (9/18). Patients aged 40 years and younger were significantly
      more likely to experience LOH than those aged 41-55 years (p = 0.04).
      Specifically, the odds of BLID loss for patients aged 40 years and younger were
      3.7 times the odds of loss for patients aged 41-55 years (95% CI, 1.1-13). Our
      findings suggest a tumor suppressor role of the BLID gene in early-onset breast
      cancer.

PMID- 21846968
TI  - Physical mapping of innate immune genes, mucins and lysozymes, and other non
      mucin proteins in the tammar wallaby (Macropus eugenii).
AB  - Sequencing of the tammar wallaby (Macropus eugenii) genome has the potential to
      be an extremely valuable resource for investigating evolutionary and
      developmental aspects of the mammalian immune system. However, the tammar wallaby
      genome has only been sequenced to a 2-fold depth and consists of small contigs,
      leaving many sequence gaps, many putative orthologs unpredicted and the location
      of genes within the genome unknown. In the case of low sequenced genomes,
      physical maps of genes on chromosomes can help identify specific genes if they
      map to conserved regions. Genes corresponding to adaptive immunity have been
      mapped in the tammar wallaby; however, genes corresponding to the innate immune
      system have not been investigated. We predict 2 types of genes important to the
      innate immune system, mucins and lysozymes, in the tammar wallaby and compare the
      predicted peptide sequences and locations of the genes with the South American
      opossum (Monodelphis domestica) and human. We use fluorescence in situ
      hybridization to physically map the genes to tammar wallaby chromosomes,
      demonstrating the importance of identifying and mapping genes when genomes have
      low sequence coverage. As mucins and lysozymes play protective roles in young
      animals, we also propose that their immunological role in developing marsupials
      warrants further investigation.

PMID- 21846969
TI  - Plasma substance P levels in patients with persistent cough.
AB  - BACKGROUND: Substance P (SP) is involved in the pathogenesis of cough in animal
      models. However, few studies in humans have been reported and the roles of SP in
      clinical cough remain obscure. OBJECTIVES: To clarify the relevance of plasma
      levels of SP in patients with persistent cough. METHODS: We studied 82 patients
      with cough persisting for at least 3 weeks and 15 healthy controls. Patients were
      classified as having asthmatic cough (cough-variant asthma and cough-predominant
      asthma; n = 61) or nonasthmatic cough (n = 21; postinfectious cough, n = 6;
      gastroesophageal reflux disease, n = 5; idiopathic cough, n = 5, and others, n =
      5). Correlations were evaluated between plasma SP levels as measured with ELISA
      and methacholine airway hyperresponsiveness (airway sensitivity and airway
      reactivity), capsaicin cough sensitivity, sputum eosinophil and neutrophil
      counts, and pulmonary function. RESULTS: Plasma SP levels were significantly
      elevated in patients with both asthmatic and nonasthmatic cough compared with
      controls [31.1 pg/ml (range 18.0-52.2) and 30.0 pg/ml (range 15.1-50.3) vs. 15.4
      pg/ml (range 11.3-23.7); p = 0.003 and p = 0.038, respectively] but did not
      differ between the two patient groups (p = 0.90). Plasma SP levels correlated
      with airway sensitivity (threshold dose of methacholine) in the patients with
      asthmatic cough (r = -0.37, p = 0.005) but not with airway reactivity, cough
      sensitivity, FEV1 values, or sputum eosinophil and neutrophil counts in either
      group. CONCLUSIONS: Increased levels of SP in plasma are associated with
      persistent cough in humans and might be related to airway sensitivity in
      asthmatic cough.

PMID- 21846970
TI  - Two candidate genes (FTO and INSIG2) for fat accumulation in four canids:
      chromosome mapping, gene polymorphisms and association studies of body and skin
      weight of red foxes.
AB  - Fat accumulation is a polygenic trait which has a significant impact on human
      health and animal production. Obesity is also an increasingly serious problem in
      dog breeding. The FTO and INSIG2 are considered as candidate genes associated
      with predisposition for human obesity. In this report we present a comparative
      genomic analysis of these 2 genes in 4 species belonging to the family Canidae -
      the dog and 3 species which are kept in captivity for fur production, i.e. red
      fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci
      by FISH and compared the entire coding sequence of INSIG2 and a fragment of the
      coding sequence of FTO. The FTO gene was assigned to the following chromosomes:
      CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24-25 (Chinese
      raccoon dog), while the INSIG2 was mapped to CFA19q17, VVU5p14, ALA24q15 and
      NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in INSIG2 and 13
      in FTO) and among them 2 were missense substitutions in the dog (23C/T, Thr>Met
      in the FTO gene and 40C/A, Arg>Ser in INSIG2). The distribution of these 2 SNPs
      was studied in 14 dog breeds. Two synonymous SNPs, one in the FTO gene (-28T>C in
      the 5'-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used
      for the association studies in red foxes (n = 390) and suggestive evidence was
      observed for their association with body weight (FTO, p < 0.08) and weight of raw
      skin (INSIG2, p < 0.05). These associations indicate that both genes are
      potential candidates for growth or adipose tissue accumulation in canids. We also
      suggest that the 2 missense substitutions found in dogs should be studied in
      terms of genetic predisposition to obesity.

PMID- 21846971
TI  - The incidence and survival of acute de novo leukemias in Estonia and in a well
      defined region of western Sweden during 1997-2001: a survey of patients aged 16
      64 years.
AB  - BACKGROUND: In a recent retrospective study, we investigated the incidence and
      survival of de novo acute leukemia (AL) patients aged 16-64 years over three 5
      year periods (1982-1996) in Estonia and in the Western Swedish Health Care
      Region. The incidence rates were similar in the two countries, but the survival
      data were highly different. Thus, relative survival at 5 years for de novo AL
      patients in Estonia was virtually negligible, whereas the corresponding figures
      for the Swedish patients increased from 20.3 to 38.9% during the study period.
      AIM: To prospectively compare the results for incidence and outcome of de novo AL
      between the two countries during 1997-2001. RESULTS: Incidence rates for de novo
      AL were lower in Estonia than in western Sweden but not significantly so.
      However, the survival for de novo AL patients in Estonia had improved
      considerably, with the relative survival at 5 years being 16.4%; such improvement
      was particularly seen in acute myeloid leukemia patients. For the Swedish
      patients, no change in survival was recorded. CONCLUSION: In Estonia, a
      remarkable improvement in outcome for young de novo AL patients was seen after
      1996. Nevertheless, relative survival for the Estonian patients had still not
      reached the levels found in the Swedish cohort.

PMID- 21846972
TI  - Classical hairy cell leukemia and its variant: a 17-year retrospective survey in
      Taiwan Chinese.
AB  - BACKGROUND: Classical hairy cell leukemia (HCL-C) and its variant (HCL-V) are
      rare chronic B-cell lymphoproliferative disorders. Only a few reports in Chinese
      patients are available. METHODS: We retrospectively reviewed 16 patients with HCL
      C and HCL-V in Taiwan over a 17-year period. RESULTS: Eight were HCL-C and 8 were
      HCL-V. All HCL accounted for 0.7% of all adult leukemias. Compared to HCL-V, HCL
      C was characterized by profound leukopenia, monocytopenia, thrombocytopenia and
      fewer circulating hairy cells. One HCL-C and 2 HCL-V patients had second
      malignancies. Seven HCL-C patients achieved hematological remission after
      splenectomy (n = 1) or 2-chlorodeoxyadenosine (n = 6). Of the 8 HCL-V patients, 6
      received splenic irradiation. Only one achieved complete remission and another
      had partial remission; relapse or disease progression was noted 13.4 or 25.7
      months later, respectively. Two of three HCL-V patients who underwent splenectomy
      had stable disease. All patients with HCL-C were alive while 3 with HCL-V
      expired. Compared to HCL-C, HCL-V had a significantly shorter leukemia-free
      survival. CONCLUSION: A relatively higher proportion of HCL-V in all HCL
      comparing to Westerners is observed. Second malignancies are common. With an
      inferior outcome and dismal response to most treatment, enrollment in a clinical
      trial should be considered for HCL-V.

PMID- 21846973
TI  - De novo acute myeloid leukemia associated with t(11;17)(q23;q25) and MLL-SEPT9
      rearrangement in an elderly patient: a case study and review of the literature.

PMID- 21846975
TI  - Validity of the current NCAA minimum weight protocol: a brief review.
AB  - Historically, collegiate wrestlers have been associated with utilizing rapid
      weight loss methods to reach a desired weight class. Following three deaths in
      1997, the National Collegiate Athletic Association (NCAA) implemented a program
      which prevents wrestlers from wrestling below a minimum weight (MW) of 5% body
      fat. Although numerous studies have investigated adolescent wrestlers, few have
      investigated collegiate wrestlers using the methods outlined by the NCAA. The
      purpose of this review paper is to outline potential problems with the current
      NCAA protocol as well as critique studies investigating the validity of methods
      to assess MW.

PMID- 21846974
TI  - Podocytes of AT2 receptor knockout mice are protected from angiotensin II
      mediated RAGE induction.
AB  - BACKGROUND/AIMS: The interaction of 'advanced glycation end products' (AGEs) and
      their receptor 'RAGE' plays an important role in diabetic nephropathy. We have
      previously found that in cultured differentiated podocytes, angiotensin II (ANG
      II) induces RAGE expression via an AT2 receptor-mediated pathway. METHODS: To
      further confirm our results in an in vivo study, AT2 receptor knockout mice (AT2(
      /-)) and wild-type mice were infused with ANG II by osmotic minipumps for 14
      days. RESULTS: As shown by immunohistochemistry, ANG II treatment of wild-type
      animals (C57BL6) allowed a significantly increased RAGE expression in renal
      podocytes in comparison to sham-operated C57BL6 mice. In contrast, RAGE
      expression in podocytes of ANG II-treated knockout mice (AT2(-/-)) was only
      moderately higher than in control animals, but significantly lower than in ANG II
      treated wild-type mice. For the AGE species Nepsilon-carboxymethyllysine, a
      similar immunohistochemical staining pattern was found. There was no significant
      change in glomerular AT1a receptor expression. However, no difference in RAGE
      mRNA expression could be found between ANG II-infused wild-type and AT2(-/-)
      animals by real-time PCR using whole kidney mRNA, presumably due to the low
      abundance of podocyte mRNA in these preparations. No effects were seen on
      glomerular apoptosis. CONCLUSION: These data support the fact that ANG II
      mediated RAGE induction in podocytes occurs via AT2 receptors. The present
      findings may suggest that not all ANG II-mediated changes in diabetic nephropathy
      can be treated with AT1 receptor blockers.

PMID- 21846976
TI  - Early programming effects of nutrition - life-long consequences?

PMID- 21846977
TI  - Epigenetic epidemiology: the rebirth of soft inheritance.
AB  - Non-communicable diseases (NCDs), such as cardiovascular disease and type 2
      diabetes, constitute the main cause of death worldwide. Eighty percent of these
      deaths occur in low- and middle-income countries, especially as these countries
      undergo socio-economic improvement following reductions in the burden of
      infectious disease. The World Health Organization predicts a substantial increase
      in the incidence of NCDs over the next decade globally. NCDs are generally
      preventable, but current approaches are clearly inadequate. New initiatives are
      needed to implement such prevention, and there needs to be greater recognition
      that early-life interventions are likely to be the most efficacious. Devising
      appropriate prevention strategies necessitates an understanding of how the
      developmental environment influences risk. Progress in this field has been slow
      due to an excessive emphasis on fixed genomic variations (hard inheritance) as
      the major determinants of disease susceptibility. However, new evidence
      demonstrates the much greater importance of early-life developmental factors,
      involving epigenetic processes and 'soft' inheritance in modulating an
      individual's vulnerability to NCD. This also offers opportunities for novel
      epigenetic biomarkers of risk or interventions targeting epigenetic pathways to
      be devised for use in early life. This may pave the way to much more effective,
      customised interventions to promote health across the life course.

PMID- 21846978
TI  - Metabolic programming in the immediate postnatal life.
AB  - The metabolic programming effects of nutritional modifications in the immediate
      postnatal life are increasingly recognized to independently contribute to the
      development of metabolic syndrome in later life. Adjustment of litter size in
      rodents has been used to induce either under- or overnourishment in the immediate
      postnatal life of the offspring. While undernourishment led to growth retardation
      in the offspring, overnourishment produced increased body weight gains,
      hyperinsulinemia and hyperleptinemia. Overnourishment during the suckling period
      induced several adaptations in the energy circuitry in the hypothalamus of the
      offspring predisposing them for the onset of obesity later in life. Another
      approach for a nutritional modification in the immediate postnatal period is the
      artificial rearing of newborn rat pups on a high-carbohydrate (HC) milk formula
      without changes in the total calorie availability. Hyperinsulinemia, immediately
      evident in the HC pups, persisted in the post-weaning period even after
      withdrawal of the HC milk. Significant alterations in pancreatic islets supported
      chronic hyperinsulinemia in the HC rats. Alterations in the gene expression of
      hypothalamic neuropeptides predisposing to hyperphagia were evident during the
      period of the HC dietary modification. The persistence of these hypothalamic
      adaptations supported the obese phenotype in adult HC rats. A transgenerational
      effect gave rise to the development of chronic hyperinsulinemia and adult-onset
      obesity in the offspring of the HC female rats. Other studies have shown that
      lactation by a diabetic, obese or malnourished mother resulted in predisposition
      for the onset of metabolic disorders in the offspring. These observations from
      animal studies on the metabolic programming effects due to altered nutritional
      experiences in the immediate postnatal life strongly suggest that altered feeding
      practices for infants (formula feeding and early introduction of infant foods)
      could contribute to the rising incidence of overweight/obesity in children and
      adults.

PMID- 21846979
TI  - Programming towards childhood obesity.
AB  - There is now considerable evidence that a constitutional susceptibility to fat
      gain is necessary for children to become obese under the pressure of an
      obesogenic environment; this is the programming towards obesity. The role of
      genetics in this programming is dominant. Besides the rare monogenic recessive
      forms of obesity secondary to mutations in genes involved in the hypothalamic
      appetite control pathways, obesity linked to mutations in melanocortin 3 and 4
      receptors are more frequent due to their dominant mode of transmission.
      Predisposition to common obesity is polygenic and involves a network of genes;
      nevertheless, more research is required to elucidate their exact role. Fetal and
      perhaps early postnatal programming is also possible. Under- and overnutrition,
      diabetes, and maternal smoking during pregnancy were shown to promote later
      obesity and may affect the central body weight regulatory system during fetal
      development. The role of early postnatal factors such as formula-feeding rather
      than breastfeeding, excess in n-6 polyunsaturated fatty acids or protein intakes,
      and excessive weight gain early in life is more questionable and needs further
      investigation. Taking into consideration that childhood obesity is a programmed
      disease should modify its clinical management. Childhood obesity should no longer
      be considered as the result of inappropriate eating habits and/or excessive
      inactivity in order to relieve the obese children's discrimination and their
      parents' guilt. Since treatment of obese children requires a substantial
      motivation to continuously fight against the programmed excessive drive to eat,
      it seems wiser to wait for children to be old enough, thus more motivated, to
      initiate energy restriction. Moreover, with the great majority of children being
      not predisposed to obesity, prevention strategies should not be addressed to the
      whole pediatric population but targeted to those children at risk. Improvement of
      knowledge on programming towards obesity is essential to develop more promising
      therapeutic and preventive approaches.

PMID- 21846980
TI  - Programming of host metabolism by the gut microbiota.
AB  - The human gut harbors a vast ensemble of bacteria that has co-evolved with the
      human host and performs several important functions that affect our physiology
      and metabolism. The human gut is sterile at birth and is subsequently colonized
      with bacteria from the mother and the environment. The complexity of the gut
      microbiota is increased during childhood, and adult humans contain 150-fold more
      bacterial genes than human genes. Recent advances in next-generation sequencing
      technology and mechanistic testing in gnotobiotic mice have identified the gut
      microbiota as an environmental factor that contributes to obesity. Germ-free mice
      are protected against developing diet-induced obesity and the underlying
      mechanisms whereby the gut microbiota contributes to host metabolism are
      beginning to be clarified. The obese phenotype is associated with increased
      microbial fermentation and energy extraction; however, other microbially
      modulated mechanisms contribute to disease progression as well. The gut
      microbiota has profound effects on host gene expression in the enterohepatic
      system, including genes involved in immunity and metabolism. For example, the gut
      microbiota affects expression of secreted proteins in the gut, which modulate
      lipid metabolism in peripheral organs. In addition, the gut microbiota is also a
      source of proinflammatory molecules that augment adipose inflammation and
      macrophage recruitment by signaling through the innate immune system. TLRs (Toll
      like receptors) are integral parts of the innate immune system and are expressed
      by both macrophages and epithelial cells. Activation of TLRs in macrophages
      dramatically impairs glucose homeostasis, whereas TLRs in the gut may alter the
      gut microbial composition that may have profound effects on host metabolism.
      Accordingly, reprogramming the gut microbiota, or its function, in early life may
      have beneficial effects on host metabolism later in life.

PMID- 21846981
TI  - Partial deafness treatment with the nucleus straight research array cochlear
      implant.
AB  - INTRODUCTION: The Nucleus Straight Research Array (SRA) cochlear implant has a
      new 25-mm electrode carrier designed to minimize insertion trauma, in particular
      allowing easy insertion via the round window. The aims of this study were to
      measure preoperative to postoperative benefit in terms of speech recognition in
      quiet and in noise in three groups of patients (electrical complement, EC;
      electrical stimulation, ES; electro-acoustic stimulation, EAS) with varying
      levels of low-frequency hearing, and to evaluate the preservation of residual
      hearing after implantation with the SRA cochlear implant. METHODS: The study
      design was prospective with sequential enrolment and within-subject comparisons:
      23 adult cochlear implant candidates were divided into three groups according to
      their level of preoperative residual hearing at 500 Hz (EC <=50 dB; 50 dB < EAS <
      80 dB; ES >=80 dB). Monosyllabic word recognition using the SRA cochlear implant
      in combination with residual low-frequency hearing was assessed at 4 and 13
      months after implantation. Hearing threshold levels were also monitored over
      time. RESULTS: Subjects across all three groups had significant improvements in
      speech recognition scores (i.e. >20 percentage points) both for listening in
      quiet (71% of subjects) and in noise (100% of subjects). The average score at 4
      months after operation for words presented in quiet was 61.7%, and in 10 dB SNR
      noise 46.5%, compared to 34.4 and 10.6% preoperatively (p < 0.001). All subjects
      retained measurable hearing at 500 Hz in the implanted ear at 4 months after the
      operation; mean increases were 19, 29 and 1 dB for the EC, EAS and ES groups (n =
      21). Across frequencies of 125-1000 Hz, the median increase in thresholds was 15
      dB up to 13 months postoperatively (n = 15). CONCLUSIONS: Speech recognition
      performance of subjects with various levels of residual low-frequency hearing was
      significantly improved with the SRA cochlear implant. A high level and rate of
      hearing preservation was achieved with the SRA implanted using a round window
      surgical technique. Subjects with preoperative low-frequency hearing levels
      between 50 and 80 dB HL (EAS group) tended to lose more hearing than those with
      either better or worse hearing.

PMID- 21846982
TI  - Successful salvage of peritoneal catheter in unresolved methicillin-resistant
      staphylococcus aureus peritonitis by combination treatment with daptomycin and
      rifampin.
AB  - Peritoneal dialysis patients are at an increased risk of Gram-positive organism
      infections because of disrupted skin barrier function, presence of a peritoneal
      catheter, and a deficient immunological system. In particular, the treatment of
      methicillin-resistant Staphylococcus aureus (MRSA) infections is clinically
      challenging. Herein, we present a case of MRSA peritonitis that showed no
      response to a 14-day treatment with intraperitoneal vancomycin. To overcome
      unresponsiveness to vancomycin, we shifted the regimen to intraperitoneal
      daptomycin (given every 6 h through manual peritoneal dialysate exchanges) and
      oral rifampin (300 mg twice daily). The peritonitis resolved without sequelae or
      relapse. We suggest daptomycin and rifampin as an alternative combination therapy
      for MRSA infections that may otherwise remain unresolved.

PMID- 21846983
TI  - The Arteriovenous fistula: lesser evil or God's blessing?

PMID- 21846984
TI  - Atherosclerosis and PTPN22: a study in coronary artery disease.
AB  - OBJECTIVES: Recently, it has been shown that PTPN22 genetic polymorphism is
      associated with phenotypes related to the risk of atherosclerosis. In the present
      note, we have searched for a possible association of PTPN22 polymorphism with
      coronary artery disease (CAD). METHODS: One hundred and thirty-four non-diabetic
      subjects admitted to hospital for CAD and 174 healthy subjects (blood donors)
      were studied. PTPN22 genotypes were determined by DNA analysis. Statistical
      analyses were performed by SPSS programs. RESULTS: In CAD patients, the
      proportion of carriers of the *T allele of PTPN22 is significantly higher
      compared to healthy controls (OR 2.66; 95% CI 1.07-6.72). CONCLUSIONS: The
      present observation confirms the association of PTPN22 phenotype with
      atherosclerosis and suggests a role of immune mechanism in the pathogenesis of
      CAD.

PMID- 21846985
TI  - Once versus twice daily gentamicin dosing for infective endocarditis: a
      randomized clinical trial.
AB  - OBJECTIVES: The aim of this randomized study was to investigate the effects of
      once versus twice daily gentamicin dosing on renal function and measures of
      infectious disease in a population with infective endocarditis (IE). METHODS:
      Seventy-one IE patients needing gentamicin treatment according to guidelines were
      randomized to either once (n = 37) or twice daily (n = 34) doses of gentamicin.
      Kidney function (glomerular filtration rate, GFR) was measured with an isotope
      method ((51)Cr-EDTA) at the beginning of treatment and at discharge. Treatment
      efficacy was assessed by C-reactive protein (CRP) time to half-life, mean CRP and
      leukocytes. RESULTS: Baseline GFR was similar in the two groups. Both groups
      displayed a significant fall in GFR from admission to discharge. The mean
      decrease in GFR was as follows: with once daily gentamicin, 17.0% (95% confidence
      interval 7.5-26.5), and with twice daily gentamicin, 20.4% (95% confidence
      interval 12.0-28.8). However, there was no significant difference in the GFR
      decrease between the once and twice daily regimens (p = 0.573). No difference in
      infection parameters was demonstrated between the two dosing regimens.
      CONCLUSIONS: A twice daily gentamicin dosing regimen is neither less nephrotoxic
      nor more efficient than a once daily regimen in the treatment of IE patients.
      When indicated, gentamicin may therefore also be administered as a single-dose
      regimen in the treatment of IE patients.

PMID- 21846986
TI  - Roles of different sources of social support on caries experience and caries
      increment in adolescents of East london.
AB  - Evidence on the contribution of social support to oral health is scarce. We first
      explored the association of social support with caries experience and the
      relative roles of support from family, friends and a special person on caries
      experience in 15-16-year-old adolescents. We then explored whether social support
      at 11-12 years of age predicts caries increment in second permanent molars over 4
      years and the relative roles of different sources of support on 4-year caries
      increment. Data from phases 1 and 3 of the Research with East London Adolescents
      Community Health Survey (RELACHS), a school-based prospective study of a
      representative sample of adolescents in East London, were used for cross
      sectional (phase 3) and longitudinal analyses (phases 1 and 3). Data were
      collected by questionnaires including the same questions on demographic
      characteristics, socioeconomic measures and the Multidimensional Scale of
      Perceived Social Support at phases 1 and 3. A questionnaire section on dental
      behaviours and an oral clinical examination were also included in phase 3. Social
      support was negatively related to both caries experience and increment
      independently of demographic characteristics, socioeconomic measures and dental
      behaviours. Furthermore, only support from a special person was significantly
      related to caries experience and increment in unadjusted and adjusted regression
      models. In conclusion, adolescents who perceived higher levels of social support
      had lower caries experience and increment. However, support from a special person
      was more relevant for these adolescents than support from family and peers.

PMID- 21846987
TI  - Evaluating the quality of life of people with dementia in residential care
      facilities.
AB  - AIMS: Our purpose was to compare recipient and caregiver perception of the
      quality of life (QoL) of people with dementia in residential care facilities and
      to identify the factors associated with their perception of QoL. METHODS:
      Residents' QoL was evaluated by both the patient and the caregiver, using the
      Quality of Life in Alzheimer's Disease and several other indices. RESULTS: The
      correlation between the self-rated QoL score and the staff-rated QoL score was
      low. CONCLUSIONS: The staff tended to underestimate QoL. The main determinants of
      QoL were the functional status and depression. Improving physical function and
      mood may be beneficial in providing a better QoL.

PMID- 21846988
TI  - Clinical course of patients with familial early-onset Alzheimer's disease
      potentially lacking senile plaques bearing the E693Delta mutation in amyloid
      precursor protein.
AB  - BACKGROUND/AIMS: Oligomeric amyloid beta (Abeta) is currently considered to
      induce Alzheimer's disease (AD). We examined 2 patients with familial AD who
      possessed the Osaka (E693Delta) mutation in amyloid precursor protein. To the
      best of our knowledge, these patients are the first AD cases presumably affected
      with Abeta oligomers in the absence of senile plaques, and they support the Abeta
      oligomer hypothesis. METHODS: We evaluated the clinical course,
      neuropsychological data, cerebrospinal fluid biomarker levels, magnetic resonance
      imaging (MRI) scans, fluorodeoxyglucose-positron emission tomography (PET) scans,
      and Pittsburgh compound B (PiB)-PET images of these patients. RESULTS: In the
      early stages, these patients developed memory disturbances in a similar rate to
      patients with sporadic AD. Despite their memory disturbances, both patients
      showed only limited brain atrophy on MRI and little amyloid accumulation on PiB
      PET. Subsequent to the development of memory disturbances, both patients suffered
      from motor dysfunction, probably due to cerebellar ataxia, and, within a few
      years, the patients fell into an apallic state. CONCLUSIONS: Familial AD patients
      with Osaka (E693Delta) mutation show severe dementia, cerebellar ataxia, and gait
      disturbances.

PMID- 21846989
TI  - Incidence of bactobilia increases over time after endoscopic sphincterotomy.
AB  - Patients with choledochocystolithiasis are usually treated by endoscopic
      retrograde cholangiography with endoscopic sphincterotomy (ES) followed by
      laparoscopic cholecystectomy (LC). LC after ES is more difficult than in
      uncomplicated gallstone disease, possibly due to bacterial colonization of the
      common bile duct. The goal of this study was to evaluate if bactobilia influences
      the peri- and postoperative outcomes. Data were obtained from a randomized trial
      on the timing of LC after ES. Ninety-six patients were randomized after ES to LC
      either within 72 h (early LC [ELC]) or in 6-8 weeks (delayed LC [DLC]). In 64 of
      96 patients bile samples were obtained peroperatively. The overall prevalence of
      bactobilia was 62.5% [40/64; 50% of ELC patients (n = 13) vs. 71.1% in the DLC
      group (n = 27); p = 0.088]. Age and group (i.e. ELC/DLC) were independent and
      significant predictors for the presence of bactobilia. The presence of bactobilia
      did not influence operating time and difficulty or conversion rate. Patients with
      bactobilia developed more biliary events in the period between ES and LC (44 vs.
      28%). After ES for choledochocystolithiasis, 62.5% of patients have bactobilia at
      the time of surgery. The prevalence of bactobilia increases with age and time.
      Patients with bactobilia tend to develop more biliary-related complications
      awaiting surgery.

PMID- 21846990
TI  - Three cases of focal embouchure dystonia: classifications and successful therapy
      using a dental splint.
AB  - BACKGROUND: Focal embouchure dystonia (FED) is a type of task-specific dystonia
      affecting wind instrument players, and it frequently ends their professional
      careers. The results of the treatments of FED in the reported literature are
      disappointing. OBJECTIVE: We report 3 patients with FED who were brass instrument
      players. In 1 patient, we evaluated the usefulness of a dental splint. METHODS
      AND RESULTS: Patient 1 was a 28-year-old trumpeter who was suffering from an
      intermittent tremor of the lower jaw. Following the usage of a dental splint, her
      symptoms disappeared completely. Patient 2 was a 29-year-old horn player with
      atonia of the lower facial muscles. In this case, medication with various drugs
      brought no benefit, and he ended his career. Patient 3 was a 43-year-old trombone
      player who suffered involuntary contractions and relaxation of the perioral
      muscles along with clumsiness of tongue movement. Extraction of double teeth and
      long-term cessation of playing for 20 years did not bring any positive effects.
      CONCLUSION: We propose that FED can be categorized into three subgroups according
      to masticatory, facial and lingual types, and that the dental splint might be a
      useful therapeutic strategy for the masticatory type of FED.

PMID- 21846991
TI  - Association of Th1/Th2-related chemokine receptors in peripheral T cells with
      disease activity in patients with multiple sclerosis and neuromyelitis optica.
AB  - We evaluated 30 patients with clinically definite multiple sclerosis (MS) and 8
      patients with neuromyelitis optica (NMO) to investigate correlations between
      Th1/Th2 balance, disease activity, effects of interferon (IFN)-beta treatment,
      and expressions of chemokine receptors CXCR3 and CCR4 on CD4+ and CD8+ T cells in
      peripheral blood. MS and NMO patients in the relapsing phase showed a
      significantly increased CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio
      compared with respective patients in the remission phase. After IFN-beta
      treatment, the CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio were
      significantly decreased compared with the relapsing phase and slightly lower than
      in the remission phase. The CD8+CXCR3+/CD8+CCR4+ ratio showed a more marked
      change associated with disease activity than CD4+ T cells in MS and NMO patients.
      Moreover, in patients in the relapsing phase of NMO, the CD4+CXCR3+/CD4+CCR4+
      ratio and CD8+CXCR3+/CD8+CCR4+ ratio were significantly higher than in MS
      patients in the relapsing phase. We confirmed marked changes in the
      CD8+CXCR3+/CD8+CCR4+ ratio according to disease activity and treatment of MS and
      NMO. Furthermore, this ratio was more strongly linked to immune and inflammatory
      activity in NMO patients than in MS patients, and may represent an important
      factor in differentiating the pathogenesis of MS and NMO.

PMID- 21846992
TI  - Correlation between progressive changes in piriform cortex and olfactory
      performance in early Parkinson's disease.
AB  - OBJECTIVES: The mechanism underlying olfactory dysfunction in Parkinson's disease
      (PD) remains unknown. The current study aims to investigate the relationship
      between sequential changes of volume change of cortex associated with olfactory
      function and degree of deficiency of olfactory performance in PD. METHODS: Based
      on the arbitrary cut-off score of olfactory performance measured by 'five odors
      olfactory detection arrays', subjects were classified into three groups: PD
      patients with olfactory impairment (OPD, n = 12), PD without olfactory impairment
      (NPD, n = 14), and healthy controls without olfactory impairment (NC, n = 26). A
      morphometric analysis of magnetic resonance images (voxel-based morphometry; VBM)
      was used to investigate cortical volume change. RESULTS: The scores of olfactory
      performance were higher in both NPD and OPD groups than in the NC group
      independent of age and disease duration, indicating that NPD subjects did have
      board line deficiency of olfaction though not meet the cut-off score for abnormal
      olfactory function. Both NPD and OPD had cortical atrophy in the parahippocampal
      gyrus (PCG), but only OPD also had change in orbitofrontal cortex (OFC).
      Correlation analysis revealed that decrement of volumes of PCG and right OFC was
      associated with decreased olfactory detection sensitivity, and the right OFC was
      also correlated to olfactory identification. However, no correlation was found
      between structural changes and the severity of the disease measured by UPDRS
      score. CONCLUSIONS: The results confirmed that atrophy in piriform cortex and
      orbitofrontal cortex is associated with olfactory dysfunction in early PD.
      Atrophy of the orbitofrontal cortex becomes significant as olfactory damage
      progresses. Volume measurement of olfaction-associated areas together with the
      assessment of olfactory function may be a sensitive indicator for the early
      diagnosis of PD.

PMID- 21846993
TI  - Sleep-related eating disorder in two patients with early-onset Parkinson's
      disease.

PMID- 21846994
TI  - Role of single-dose clostridiopeptidase A collagenase in peritoneal adhesions.
AB  - BACKGROUND: To evaluate the effect of clostridiopeptidase A collagenase (CAC) in
      a rat model of postoperative peritoneal adhesion (PPA). METHODS: Forty rats were
      divided into four equal groups. In group 1, 1 g CAC was injected into the
      peritoneal cavity. In group 2, adhesions were generated. In group 3, adhesions
      were generated, and, 10 days later, the area with PPAs was covered with 1 g CAC.
      In group 4, adhesions were generated and the area was covered immediately with 1
      g CAC. All rats were sacrificed on postoperative day 10, and adhesions were
      scored both macroscopically and microscopically. RESULTS: Mean macroscopic
      adhesion scores in groups 1-4 were 0, 2.9 +/- 0.21, 2.55 +/- 0.16, and 1.3 +/- 1,
      respectively (p = 0.0001). The mean macroscopic adhesion score in group 4 was
      lower than that in group 2 (p = 0.045). The mean macroscopic adhesion score in
      group 4 was lower than that in group 3, but the value was not statistically
      different (p = 0.098). Mean microscopic values were 0, 2.8 +/- 0.42, 2.5 +/-
      0.52, and 1.3 +/- 0.67, respectively (p< 0.0001). The group 4 score was lower
      than those of groups 2 (p = 0.01) and 3 (p = 0.025). DISCUSSION: A single dose of
      CAC reduces PPA formation. CAC, however, is not effective on already formed PPAs.

PMID- 21846995
TI  - Modelling the effects of penetrance and family size on rates of sporadic and
      familial disease.
AB  - BACKGROUND/AIMS: Many complex diseases show a diversity of inheritance patterns
      ranging from familial disease, manifesting with autosomal dominant inheritance,
      through to simplex families in which only one person is affected, manifesting as
      apparently sporadic disease. The role of ascertainment bias in generating
      apparent patterns of inheritance is often overlooked. We therefore explored the
      role of two key parameters that influence ascertainment, penetrance and family
      size, in rates of observed familiality. METHODS: We develop a mathematical model
      of familiality of disease, with parameters for penetrance, mutation frequency and
      family size, and test this in a complex disease: amyotrophic lateral sclerosis.
      RESULTS: Monogenic, high-penetrance variants can explain patterns of inheritance
      in complex diseases and account for a large proportion of those with no apparent
      family history. With current demographic trends, rates of familiality will drop
      further. For example, a variant with penetrance 0.5 will cause apparently
      sporadic disease in 12% of families of size 10, but 80% of families of size 1. A
      variant with penetrance 0.9 has only an 11% chance of appearing sporadic in
      families of a size similar to those of Ireland in the past, compared with 57% in
      one-child families like many in China. CONCLUSIONS: These findings have
      implications for genetic counselling, disease classification and the design of
      gene-hunting studies. The distinction between familial and apparently sporadic
      disease should be considered artificial.

PMID- 21846996
TI  - Identification by differential tissue proteome analysis of talin-1 as a novel
      molecular marker of progression of hepatocellular carcinoma.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is characterized by a multistage
      process of tumor progression. This study addressed its molecular features to
      identify novel protein candidates involved in HCC progression. METHODS: Using
      liquid chromatography-tandem mass spectrometry, proteomes of 4 early HCCs and 4
      non-HCC tissues derived from 2 cases of liver transplant surgery were compared
      with respect to the separation profiles of their tryptic peptides.
      Immunohistochemistry was performed on 106 HCC nodules to confirm the results of
      the proteomic analysis. RESULTS: Statistical analysis of the profiles selected
      the peptide peaks differentiating HCC from non-HCC. A database search of the
      tandem mass spectrometry data from those peptide peaks identified 61 proteins,
      including a cytoskeletal protein, talin-1, as upregulated in HCC. Talin-1
      expression levels in HCC nodules were significantly associated with the
      dedifferentiation of HCC (p = 0.001). A follow-up survey of the examined clinical
      cases revealed a correlation between talin-1 upregulation and a shorter time to
      recurrence after resection (p = 0.039), which may be related to the higher rate
      of portal vein invasion in HCCs with talin-1 up-regulation (p = 0.029).
      CONCLUSIONS: Proteomic analysis led to identification of talin-1 as a promising
      HCC marker. Talin-1 upregulation is associated with HCC progression and may serve
      as a prognostic marker.

PMID- 21846997
TI  - Clofibrate relaxes the longitudinal smooth muscle of the mouse distal colon
      through calcium-mediated desensitisation of contractile machinery.
AB  - Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a ligand
      activated transcription factor that exerts strong effects on metabolic pathways.
      Our aim was to elucidate the effect of clofibrate, a PPAR-alpha agonist, on the
      longitudinal muscle of the mouse distal colon. We initially found that clofibrate
      induced a relaxation response in this muscle. Notably, the PPAR-alpha antagonists
      GW9662 and T0070907 did not attenuate this clofibrate-induced relaxation. The
      structurally related PPAR-alpha agonists fenofibrate and bezafibrate induced
      relaxation in the distal colon as effectively as clofibrate. In contrast, wy
      14643, which activates PPAR-alpha more selectively than clofibrate, had no
      effect. Furthermore, clofibrate-induced relaxation was not affected by N-nitro-L
      arginine, an NO synthase inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3- a]quinoxaline-1
      one, a soluble guanylate cyclase inhibitor, or H89, a protein kinase A inhibitor.
      Tetrodotoxin, an Na+ channel blocker, and glibenclamide, apamin, charybdotoxin
      and XE991, various K+ channel blockers, had no effect on clofibrate-induced
      relaxation. Importantly, clofibrate induced a relaxation response that was not
      accompanied by any alteration in the cytoplasmic Ca2+ concentration in the
      longitudinal muscle of the mouse distal colon. Moreover, calyculin A, a myosin
      light-chain phosphatase (MLCP) inhibitor, attenuated clofibrate-induced
      relaxation. Our findings indicate that clofibrate relaxes the longitudinal smooth
      muscle of the mouse distal colon by regulating MLCP activity.

PMID- 21846998
TI  - Effects of pioglitazone and rosiglitazone on vascular function of mesenteric
      resistance arteries in rat genetic hypertension.
AB  - Glitazones exhibit beneficial effects in the vascular system, both on large
      vessels and at a microcirculatory level. We previously reported the effects of
      glitazones in the aorta of spontaneously hypertensive rats (SHR). We focus now on
      the acute and long-term actions of these drugs on mesenteric resistance arteries
      of the SHR. Incubation with pioglitazone or rosiglitazone (10-5 mol/l) improved
      endothelium-dependent relaxations to acetylcholine and the endothelial modulation
      of phenylephrine contractions. Acetylcholine relaxations that were abolished by
      N(G)-nitro-L-arginine methylester were partly recovered by the glitazones, but no
      effects of these drugs were observed in the presence of indomethacin or
      indomethacin + L-NAME. Glitazones did not change the contractions to U46619 or
      the endothelium-independent relaxation to sodium nitroprusside. Three-week oral
      pioglitazone or rosiglitazone treatment (3 and 10 mg/kg/day, respectively)
      confirmed the acute experiments. Thus, in microvessels, glitazones improve
      endothelial function in such a way that they do not alter endothelial nitric
      oxide release but reduce the production of vasoconstrictor prostanoids from
      endothelial cells.

PMID- 21846999
TI  - Capsaicin induces reflex scratching in inflamed skin.
AB  - We investigated whether capsaicin induces itching in skin with existing
      inflammation. We induced skin inflammation by intradermal injection of complete
      Freund's adjuvant (CFA) in the neck of mice. Four days later, we injected
      capsaicin in the same area and counted the number of scratching bouts for 30 min.
      We examined potential effects on pain in parallel experiments in which CFA and
      capsaicin were intradermally injected into hind paws. We used the time spent
      licking the hind paws during the 15 min after capsaicin injection as an estimate
      of pain. Capsaicin injection into the skin pretreated with CFA, but not into
      healthy skin, induced scratching. The scratching behavior was reduced by
      pretreatment with naloxone or capsazepine, selective antagonists for transient
      receptor potential vanilloid receptor-1 (TRPV1), but not morphine or mepyramine,
      selective antagonists for histamine 1 receptor. In animals injected with
      capsaicin into the hind paws, licking behavior was significantly inhibited via a
      MU-receptor-dependent mechanism. Our results show that TRPV1 activation, which
      normally induces pain, evokes an itch-related response in the presence of
      inflammation. This model may be interesting for future studies to explore the
      mechanism of a painful stimuli-induced itch observed under pathological
      conditions.

PMID- 21847001
TI  - The negative symptoms of schizophrenia: category or continuum?
AB  - Negative symptoms have been considered to be specific to schizophrenia or a
      subtype of schizophrenia: the deficit syndrome. In other words, these symptoms
      have been considered to be categorically different from other forms of human
      behavior and experience, whether they occur in healthy persons or patients with
      other psychiatric disorders. In this paper, we advocate a dimensional approach to
      negative symptoms, which is supported by two main arguments. First, enduring
      negative symptoms can even be observed in a variety of psychiatric disorders and
      they are not specific to schizophrenia. Second, we review evidence that negative
      symptoms show a continuous distribution from apparently healthy subjects to those
      with a fully developed clinical syndrome. Although the evidence does not allow
      for a definite decision concerning the dimensional distribution of negative
      symptoms, it certainly justifies exploring a dimensional approach with respect to
      its clinical and scientific utility. Understanding negative symptoms as a
      variation of normal mental processes will strengthen the development of
      neurocognitive models and treatment approaches.

PMID- 21847000
TI  - Fluorofenidone attenuates diabetic nephropathy and kidney fibrosis in db/db mice.
AB  - BACKGROUND/AIMS: Fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF
      PD], a novel pyridone agent, showed potent antifibrotic properties. The aim of
      the present study was to investigate the effects of AKF-PD on diabetic
      nephropathy and kidney fibrosis, and to obtain an insight into its mechanisms of
      action. METHODS: We administered AKF-PD to diabetic db/db mice for 12 weeks.
      Moreover, we performed in vitro cultures using murine mesangial cells exposed to
      high ambient glucose concentrations. RESULTS: AKF-PD reduced renal hypertrophy,
      mesangial matrix expansion and albuminuria in the db/db mice. The upregulated
      expression of alpha1(I)- and alpha1(IV)-collagen and fibronectin mRNAs,
      transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha
      SMA), and tissue inhibitors of metalloproteinase 1 (TIMP-1) mRNAs and proteins
      was inhibited by AKF-PD treatment in the renal cortex of db/db mice. The maximal
      effective dose of AKF-PD was about 500 mg/kg body weight. AKF-PD inhibited the
      upregulated expression of alpha1(I)- and alpha1(IV)-collagens, TGF-beta1, TIMP-1
      and alpha-SMA induced by high glucose concentrations in cultured mesangial cells.
      CONCLUSIONS: Our data indicate that AKF-PD diminishes the abnormal accumulation
      of mesangial matrix through the inhibition of upregulated expression of TGF-beta
      target genes in kidneys of db/db mice, resulting in attenuation of renal fibrosis
      and amelioration of renal dysfunction despite persistent hyperglycemia.
      Therefore, AKF-PD, a potent antifibrotic agent, holds great promise in the
      treatment of diabetic nephropathy.

PMID- 21847002
TI  - Early predictors of separation anxiety disorder: early stranger anxiety, parental
      pathology and prenatal factors.
AB  - OBJECTIVE: The present study seeks to extend research on the etiology of
      separation anxiety disorder (SAD) in a German-speaking sample by examining
      differences between children with SAD and healthy comparisons, using a
      retrospective-reporting paradigm. METHOD: The sample included 106 children with
      SAD and 44 healthy children between the ages of 4 and 14 years. Parents completed
      questionnaires and structured clinical interviews to assess parental pathology,
      pregnancy variables and strong early stranger anxiety. RESULTS: Children with SAD
      were more likely than healthy children to have had a phase of stronger stranger
      anxiety in infancy. Further, early stranger anxiety remained a significant
      predictor of SAD after controlling for maternal depression. Meaningful effects
      were not found for the influence of parental age at birth or other pregnancy
      factors. CONCLUSION: This study provides beginning evidence of the potential
      predictive value of strong stranger anxiety in distinguishing children with SAD
      from those with no disorder, above and beyond the influence of parental
      pathology.

PMID- 21847003
TI  - The representation of early onset depression by ICD-9 and ICD-10 categories.
AB  - BACKGROUND: Concepts of affective disorders have not received substantial
      validation in childhood and adolescence even after the theoretical separation
      between neurotic and endogenous depression was changed. The aim of this study was
      to assess differences in children and adolescents with neurotic and endogenous
      depression according to ICD-9 and depression according to ICD-10 with regard to
      the severity of different symptoms as well as anamnestic and psychosocial risk
      factors. SAMPLING AND METHODS: Data of 33 and 88 patients (classified according
      to ICD-9 and ICD-10, respectively) with a confirmed diagnosis of depression were
      included. In a standardized study protocol, sociodemographic data, family
      history, psychopathological symptoms and psychosocial and environmental factors
      were analyzed. RESULTS: Patients diagnosed with endogenous depression more
      frequently had a positive family history of psychiatric disorders and had more
      comorbid symptoms in comparison to those with neurotic depression. Group
      comparisons of the ICD-9 and ICD-10 demonstrated fewer abnormal psychosocial and
      environmental factors and fewer affective symptoms in the ICD-9 sample. Logistic
      regression revealed predictors for endogenous depression in the ICD-9 sample and
      severe depression in the ICD-10 sample. CONCLUSIONS: Neurotic depression might
      represent a subthreshold depression diagnosis compared with endogenous
      depression. The present study was limited by small and different sample sizes and
      the fact that dysthymia was not classified within the ICD-10 diagnosis.

PMID- 21847004
TI  - Alexithymia and personality disorder functioning styles in paranoid
      schizophrenia.
AB  - OBJECTIVES: Personality disorder functioning styles might contribute to the
      inconclusive findings about alexithymic features in schizophrenia. We therefore
      studied the relationship between alexithymia and personality styles in paranoid
      schizophrenia. METHODS: We administered the Chinese versions of the Toronto
      Alexithymia Scale (TAS-20), the Parker Personality Measure (PERM), the Positive
      and Negative Syndrome Scale as well as the Hamilton Anxiety and Depression Scales
      to 60 paranoid schizophrenia patients and 60 healthy control subjects. RESULTS:
      Patients scored significantly higher on the Positive and Negative Syndrome Scale,
      TAS 'difficulty identifying feelings' and 'difficulty describing feelings',
      Hamilton Depression Scale and most PERM scales. In healthy subjects, difficulty
      identifying feelings predicted the PERM 'dependent' style, and the Hamilton
      Anxiety Scale predicted difficulty identifying feelings and difficulty describing
      feelings. In patients, difficulty identifying feelings nonspecifically predicted
      all the PERM scales; by contrast, the PERM 'antisocial' style predicted
      difficulty identifying feelings, the 'avoidant' style predicted difficulty
      describing feelings, and the 'histrionic' and 'paranoid (-)' styles predicted
      'externally oriented thinking'. CONCLUSIONS: Personality disorder functioning
      styles - instead of anxiety, depression, psychotic symptoms or disease duration -
      were specifically associated with alexithymia scales in our patients, which sheds
      light on a cognitive-personological substrate in paranoid schizophrenia on the
      one hand, and calls for a longitudinal design to discover how premorbid or
      postacute residual personality styles contribute to the sluggish disorder on the
      other.

PMID- 21847005
TI  - Factor analysis of the scale of prodromal symptoms: differentiating between
      negative and depression symptoms.
AB  - BACKGROUND: This study examines the ability of the Scale of Prodromal Symptoms
      (SOPS) to differentiate between negative and depression symptoms in a young help
      seeking ultrahigh risk (UHR) group. METHODS: SOPS data of 77 help-seeking
      patients at UHR for psychosis were analyzed with an exploratory factor analysis.
      The extracted Depression factor was validated with the Beck Depression Inventory
      (BDI). The extracted SOPS Negative symptoms factor was validated with the
      Negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS).
      RESULTS: Four factors were extracted from the SOPS: a negative, depression,
      disorganized and positive factor. The Negative symptom factor consisted of three
      items (N1: social anhedonia and withdrawal, N3: decreased expression of emotion;
      N4: decreased experience of emotions and self), and could be validated with the
      PANSS Negative symptoms subscale. The Depression factor was also made up of three
      items (G2: dysphoric mood, G4: impaired tolerance to normal stress, and D4:
      personal hygiene/social attentiveness), and could be validated with the BDI.
      CONCLUSIONS: Our results suggest that 3 items of the Negative symptoms subscale
      of the SOPS, 2 items of the General and 1 item of the Disorganization subscale
      differentiate validly between negative and depression symptoms in an UHR
      population.

PMID- 21847006
TI  - Examination of anomalous self-experience in first-episode psychosis: interrater
      reliability.
AB  - BACKGROUND: The growing research focus on early detection of schizophrenia has
      fostered an increasing interest in the nonpsychotic experiential anomalies that
      may antedate schizophrenia spectrum disorders and assist early differential
      diagnosis. The Examination of Anomalous Self-Experience (EASE) is a
      phenomenologically inspired checklist, specifically designed to support the
      comprehensive assessment of these characteristic subjective experiences. AIM: To
      assess the interrater reliability of the EASE. SAMPLING AND METHODS: Twenty-five
      first-episode psychosis (FEP) patients were interviewed with the EASE. Videotaped
      interviews were blindly reevaluated. Internal consistency, overall interrater
      correlation and item interrater agreement (Cohen's kappa) were estimated.
      RESULTS: The EASE showed good to excellent internal consistency across the two
      raters (Cronbach's alpha above 0.87) and an overall inter-rater correlation above
      0.80 (Spearman's rho, p < 0.001). The average kappa of the EASE was 0.65, ranging
      from 0.51 to 0.73 over the 5 domains; kappa values at an item level were very
      good in 9 items, good in 20 items, moderate in 11 items and fair in 4 items.
      CONCLUSION: The EASE provides a reliable and internally consistent clinical tool
      for the assessment of subjective experience in FEP patients, suggesting that this
      instrument could usefully supplement standard clinical assessments during the
      onset phase of psychosis.

PMID- 21847007
TI  - Enhanced skin wound healing by a sustained release of growth factors contained in
      platelet-rich plasma.
AB  - Platelet-rich plasma (PRP) contains growth factors that promote tissue
      regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts
      the sustained release of growth factors with affinity for heparin. Here, we
      hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts
      sustained release of several growth factors contained in PRP and promotes skin
      wound healing. The release of fibroblast growth factor 2, platelet-derived growth
      factor-BB, and vascular endothelial growth factor contained in PRP from HCF was
      sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP),
      or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds
      in mice with HCF-PRP resulted in much faster wound closure as well as dermal and
      epidermal regeneration at day 12 compared to treatment with either C-PRP or F
      PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least
      partially due to enhanced angiogenesis in the wound beds. Therefore, this method
      could be useful for skin wound treatment.

PMID- 21847008
TI  - In vitro migration capacity of human adipose tissue-derived mesenchymal stem
      cells reflects their expression of receptors for chemokines and growth factors.
AB  - The homing properties of adipose tissue-derived mesenchymal stem cells (AdMSCs)
      have stimulated intravenous applications for their use in stem cell therapy.
      However, the soluble factors and corresponding cellular receptors responsible for
      inducing chemotaxis of AdMSCs have not yet been reported. In the present study,
      the migration capacity of human AdMSCs (hAdMSCs) toward various cytokines or
      growth factors (GFs) and the expression of their receptors were determined. In a
      conventional migration assay, PDGF-AB, TGF-beta1, and TNF-alpha showed the most
      effective chemoattractant activity. When AdMSCs were preincubated with various
      chemokines or GF, and then allowed to migrate toward medium containing 10% FBS,
      those preincubated with TNF-alpha showed the highest migratory activity. Next,
      hAdMSCs were either preincubated or not with TNF-alpha, and allowed to migrate in
      response to various GFs or chemokines. Prestimulation with TNF-alpha increased
      the migration activity of hAdMSCs compared to unstimulated hAdMSCs. When analyzed
      by FACS and RT-PCR methods, hAdMSCs were found to express C-C chemokine receptor
      type 1 (CCR1), CCR7, C-X-C chemokine receptor type 4 (CXCR4), CXCR5, CXCR6, EGF
      receptor, fibroblast growth factor receptor 1, TGF-beta receptor 2, TNF receptor
      superfamily member 1A, PDGF receptor A and PDGF receptor B at both the protein
      and the mRNA levels. These results indicate that the migration capacity of
      hAdMSCs is controlled by various GFs and chemokines. Prior in vitro modulation of
      the homing capacity of hAdMSCs could stimulate their movement into injured sites
      in vivo when administered intravenously, thereby improving their therapeutic
      potential.

PMID- 21847009
TI  - A prevascularized tissue engineering chamber supports growth and function of
      islets and progenitor cells in diabetic mice.
AB  - Recent studies have shown that type 1 diabetes can be reversed in a murine model
      by islet transplantation to a vascularized tissue engineering chamber. In
      preliminary experiments using a prevascularized chamber we observed that islet
      grafts not functioning initially can show a delayed onset of function several
      weeks after implantation. We sought to characterize this phenomenon. Islets were
      transplanted into prevascularized tissue engineering chambers based on the
      epigastric vessels in streptozotocin induced diabetic C57BL/6J mice. Animals were
      transplanted with 500 islets and observed at 1, 4, 8 and 16 weeks post
      transplantation. Weekly blood glucose (BG) measurements revealed an average onset
      of maintained graft function 6.8 weeks post transplantation. Graft function was
      proven by a return to a diabetic state following chamber removal. Mature grafts
      showed islet tissue clustered together within the tissue construct. The quantity
      of endocrine tissue staining positive for insulin correlated with graft function
      at 8 and 16 weeks. However, at 1 and 4 weeks, islet tissue was not evidently
      visible as observed by endocrine staining. All islet tissue showed dense
      vascularization and sporadic sympathetic innervation, irrespective of the graft's
      function. Immunopositive cells for Cytokeratin-7 and -19 were observed in the
      grafts at early time points and hormone producing cells appear to have been
      differentiated from these progenitors. Our data demonstrates that pancreatic duct
      derived progenitors remain viable in vivo and eventually differentiate and mature
      to functional islets following transplantation. Our prevascularized tissue
      engineering chamber in the groin supports maturation and function of the grafted
      tissue by two months after implantation.

PMID- 21847010
TI  - Substrate and product specificities of SET domain methyltransferases.
AB  - SET domain lysine methyltransferases (KMTs) catalyze the site- and state-specific
      methylation of lysine residues in histone and non-histone substrates. These
      modifications play fundamental roles in transcriptional regulation,
      heterochromatin formation, X chromosome inactivation and DNA damage response, and
      have been implicated in the epigenetic regulation of cell identity and fate. The
      substrate and product specificities of SET domain KMTs are pivotal to eliciting
      these effects due to the distinct functions associated with site and state
      specific protein lysine methylation. Here, we review advances in understanding
      the molecular basis of these specificities gained through structural and
      biochemical studies of the human methyltransferases Mixed Lineage Leukemia 1
      (MLL1, also known as KMT2A) and SET7/9 (KMT7). We conclude by exploring the
      broader implications of these findings on the biological functions of protein
      lysine methylation by SET domain KMTs.

PMID- 21847011
TI  - TCF21 and PCDH17 methylation: An innovative panel of biomarkers for a
      simultaneous detection of urological cancers.
AB  - The three main types of urological cancers are mostly curable by surgical
      resection, if early detected. We aimed to identify novel DNA methylation
      biomarkers common to these three urological cancers, potentially suitable for non
      invasive testing. From a candidate list of markers created after gene expression
      assessment of pharmacologically treated cell lines and tissue samples, two genes
      were selected for further validation. Methylation levels of these genes were
      quantified in a total of 12 cancer cell lines and 318 clinical samples. PCDH17
      and TCF21 methylation levels provided a sensitivity rate of 92% for bladder
      cancer, 67% for renal cell tumors and 96% for prostate cancer. Methylation levels
      were significantly different from those of cancer free individuals (n = 37) for
      all tumor types (p < 0.001), providing 83% sensitivity and 100% specificity for
      cancer detection. Although in urine samples the sensitivity was 60%, 32% and 26%
      for bladder, renal, and prostate tumors, respectively (39% overall), absolute
      specificity was retained. We identified novel and highly specific methylation
      markers common to the three main urological cancers. However, additional efforts
      are required to increase the assay's sensitivity, enabling the simultaneous non
      invasive screening of urological tumors in a single voided urine analysis.

PMID- 21847012
TI  - Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients
      and dialysis patients.
AB  - BACKGROUND: The (H1N)1v influenza virus infection emerged in 2009 as a serious
      disease in targeted populations. Herein, we report on the tolerability and
      efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients.
      METHODS: 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12
      patients treated with peritoneal dialysis (PDP), 7 patients treated with
      haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted
      vaccine injection, and RTRs received two unadjuvanted vaccine injections within a
      21-day period. Serologic response was defined as a haemagglutination inhibition
      titre of > 40 (seroprotection) and/or at least a four-fold increase in antibody
      titre from baseline (seroconversion). RESULTS: Seroprotection rate after
      vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p =
      0.001). Serologic response was similar in PDPs and HDPs. CONCLUSIONS: Serologic
      response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was
      low in RTRs as compared to DPs.

PMID- 21847015
TI  - Sublethal concentrations of salicylic acid decrease the formation of reactive
      oxygen species but maintain an increased nitric oxide production in the root apex
      of the ethylene-insensitive never ripe tomato mutants.
AB  - The pattern of salicylic acid (SA)-induced production of reactive oxygen species
      (ROS) and nitric oxide (NO) were different in the apex of adventitious roots in
      wild-type and in the ethylene-insensitive never ripe (Nr) mutants of tomato
      (Solanum lycopersicum L. cv Ailsa Craig). ROS were upregulated, while NO remained
      at the control level in apical root tissues of wildtype plants exposed to
      sublethal concentrations of SA. In contrast, Nr plants expressing a defective
      ethylene receptor displayed a reduced level of RO S and a higher NO content in
      the apical root cells. In wild-type plants NO production seems to be RO S(H2O2)
      dependent at cell death-inducing concentrations of SA, indicating that ROS and NO
      may interact to trigger oxidative cell death. In the absence of significant RO S
      accumulation, the increased NO production caused moderate reduction in cell
      viability in root apex of Nr plants exposed to 10(-3) M SA. This suggests that a
      functional ethylene signaling pathway is necessary for the control of ROS and NO
      production induced by SA.

PMID- 21847013
TI  - RNA-binding proteins with prion-like domains in ALS and FTLD-U.
AB  - Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) is a
      debilitating, and universally fatal, neurodegenerative disease that devastates
      upper and lower motor neurons. The causes of ALS are poorly understood. A central
      role for RNA-binding proteins and RNA metabolism in ALS has recently emerged. The
      RNA-binding proteins, TDP-43 and FUS, are principal components of cytoplasmic
      inclusions found in motor neurons of ALS patients and mutations in TDP-43 and FUS
      are linked to familial and sporadic ALS. Pathology and genetics also connect TDP
      43 and FUS with frontotemporal lobar degeneration with ubiquitin-positive
      inclusions (FTLD-U). It was unknown whether mechanisms of FUS aggregation and
      toxicity were similar or different to those of TDP-43. To address this issue, we
      have employed yeast models and pure protein biochemistry to define mechanisms
      underlying TDP-43 and FUS aggregation and toxicity, and to identify genetic
      modifiers relevant for human disease. We have identified prion-like domains in
      FUS and TDP-43 and provide evidence that these domains are required for
      aggregation. Our studies have defined key similarities as well as important
      differences between the two proteins. Collectively, however, our findings lead us
      to suggest that FUS and TDP-43, though similar RNA-binding proteins, likely
      aggregate and confer disease phenotypes via distinct mechanisms.

PMID- 21847016
TI  - Changes in thylakoid membrane thickness associated with the reorganization of
      photosystem II light harvesting complexes during photoprotective energy
      dissipation.
AB  - Using freeze-fracture electron microscopy we have recently shown that non
      photochemical quenching (NPQ), a mechanism of photoprotective energy dissipation
      in higher plant chloroplasts, involves a reorganization of the pigment-protein
      complexes within the stacked grana thylakoids. Photosystem II light harvesting
      complexes (LHCII) are reorganized in response to the amplitude of the light
      driven transmembrane proton gradient (DeltapH) leading to their dissociation from
      photosystem II reaction centers and their aggregation within the membrane1. This
      reorganization of the PSII-LHCII macrostructure was found to be enhanced by the
      formation of zeaxanthin and was associated with changes in the mobility of the
      pigment-protein complexes therein1. We suspected that the structural changes we
      observed were linked to the DeltapH-induced changes in thylakoid membrane
      thickness that were first observed by Murikami and Packer. Here using thin
      section electron microscopy we show that the changes in thylakoid membrane
      thickness do not correlate with DeltapH per se but rather the amplitude of NPQ
      and is thus affected by the de-epoxidation of the LHCII bound xanthophyll
      violaxanthin to zeaxanthin. We thus suggest that the change in thylakoid membrane
      thickness occurring during NPQ reflects the conformational change within LHCII
      proteins brought about by their protonation and aggregation within the membrane

PMID- 21847014
TI  - Insoluble cellular prion protein and its association with prion and Alzheimer
      diseases.
AB  - The soluble cellular prion protein (PrP(C)) is best known for its association
      with prion disease (PrD) through its conversion to a pathogenic insoluble isoform
      (PrP(Sc)). However, its deleterious effects independent of PrP(Sc) have recently
      been observed not only in PrD but also in Alzheimer disease (AD), two diseases
      which mainly affect cognition. At the same time, PrP(C) itself seems to have
      broad physiologic functions including involvement in cognitive processes. The
      PrP(C) that is believed to be soluble and monomeric has so far been the only PrP
      conformer observed in the uninfected brain. In 2006, we identified an insoluble
      PrP(C) conformer (termed iPrP(C) ) in uninfected human and animal brains.
      Remarkably, the PrP(Sc) -like iPrPC shares the immunoreactivity behavior and
      fragmentation with a newly-identified PrP(Sc) species in a novel human PrD termed
      variably protease-sensitive prionopathy. Moreover, iPrP(C) has been observed as
      the major PrP species that interacts with amyloid beta (Abeta) in AD. This
      article highlights evidence of PrP involvement in two putatively beneficial and
      deleterious PrP-implicated pathways in cognition, and hypothesizes first, that
      beneficial and deleterious effects of PrP(C) are attributable to the chameleon
      like conformation of the protein and second, that the iPrP(C) conformer is
      associated with PrD and AD.

PMID- 21847017
TI  - V-ATPase dysfunction under excess zinc inhibits Arabidopsis cell expansion.
AB  - Although zinc is an essential micronutrient for all living organisms, zinc is
      harmful to cells at high levels. In the presence of excess zinc, plants exhibit
      several major symptoms, including root growth inhibition, abnormal root hair
      morphology and chlorosis. To dissect the molecular mechanisms underlying the
      effects of excess zinc on plant cells, we used aniTRA Q-based quantitative
      proteomics approach to analyze the microsomal protein profiles of Arabidopsis
      roots from wild-type (WT) plants and de-etiolated 3-1 (det3-1), a vacuolar H+ -AT
      Pase (V-AT Pase) subunit C-defective mutant. A comparative analysis of the iTRA Q
      data from WT and det3-1 plants exposed to excess zinc suggests that the reduction
      in V-AT Pase subunit levels and its activity are the cause of the symptoms of
      zinc toxicity, including the inhibition of cell expansion. Provided that reduced
      V-AT Pase activity in the trans-Golgi network (TGN) alone can inhibit cell
      expansion, it is possible that the det3-1 mutant phenotype is caused mainly by a
      defect in TGN acidification, leading to reduced cell wall component trafficking
      and cell expansion in the presence of excess zinc. To evaluate the contribution
      of V-AT Pase activity to vacuolar acidification under excess zinc, the vacuolar
      pH was measured. Our results indicate clear alkalinization of deep cell vacuoles
      treated with 300 MUM ZnSO4.

PMID- 21847018
TI  - Grasshopper oral secretions increase salicylic acid and abscisic acid levels in
      wounded leaves of Arabidopsis thaliana.
AB  - Recent investigations showed that the model plant Arabidopsis thaliana
      specifically responds to herbivory-associated molecular patterns by activating a
      sophisticated signaling network. The lipase activity of insect oral secretions
      was shown to elevate oxylipin levels when applied to puncture wounds in leaves.
      The results also demonstrated that the oral secretions of the generalist
      Schistocerca gregaria contained other, probably non-proteinous, elicitors of
      plant defense responses which induced mitogen-activated protein kinases, calcium
      signaling and ethylene levels. This addendum presents data on the levels of
      additional phytohormones that are elevated after application of S. gregaria oral
      secretion to wounded leaves. Abscisic acid and salicylic acid levels are
      significantly elevated after elicitation with S. gregaria oral secretions, adding
      another layer of complexity to the herbivory-induced response of A. thaliana.

PMID- 21847019
TI  - A friend in need is a friend indeed: understanding stress-associated
      transcriptional networks of plant metabolism using cliques of coordinately
      expressed genes.
AB  - The response of plants to environmental cues, particularly stresses, involves the
      coordinated induction or repression of gene expression. In a previous study, we
      developed a bioinformatics approach to analyze the mutual expression pattern of
      genes encoding transcription factors and metabolic enzymes upon exposure of
      Arabidopsis plants to abiotic and biotic stresses. The analysis resulted in three
      gene clusters, each displaying a unique expression pattern. In the present
      addendum, we address the composition of each of these three clusters in regard to
      the functional identity of their encoded proteins as enzymes or transcription
      factors.

PMID- 21847020
TI  - Effects of mechanostimulation on gravitropism and signal persistence in flax
      roots.
AB  - Gravitropism describes curvature of plants in response to gravity or differential
      acceleration and clinorotation is commonly used to compensate unilateral effect
      of gravity. We report on experiments that examine the persistence of the gravity
      signal and separate mechanostimulation from gravistimulation. Flax roots were
      reoriented (placed horizontally for 5, 10 or 15 min) and clinorotated at a rate
      of 0.5 to 5 rpm either vertically (parallel to the gravity vector and root axis)
      or horizontally (perpendicular to the gravity vector and parallel to the root
      axis). Image sequences showed that horizontal clinorotation did not affect root
      growth rate (0.81 +/- 0.03 mm h-1) but vertical clinorotation reduced root growth
      by about 7%. The angular velocity (speed of clinorotation) did not affect growth
      for either direction. However, maximal curvature for vertical clinorotation
      decreased with increasing rate of rotation and produced straight roots at 5 rpm.
      In contrast, horizontal clinorotation increased curvature with increasing angular
      velocity. The point of maximal curvature was used to determine the longevity
      (memory) of the gravity signal, which lasted about 120 min. The data indicate
      that mechanostimulation modifies the magnitude of the graviresponse but does not
      affect memory persistence.

PMID- 21847021
TI  - Overexpression of a pea DNA helicase 45 in bacteria confers salinity stress
      tolerance.
AB  - Salinity stress is one of the major factors negatively affecting growth and
      productivity in living organisms including plants and bacteria resulting in
      significant losses worldwide. Therefore, it would be fruitful to develop salinity
      stress tolerant useful species and also to understand the mechanism of stress
      tolerance. The pea DNA helicase 45 (PDH45) is a DNA and RNA helicase, homologous
      to eukaryotic translation initiation factor 4A (eIF-4A) and is involved in
      various processes including protein synthesis, maintaining the basic activities
      of the cell, upregulation of topoisomerase I activity and salinity stress
      tolerance in plant, but its role in salinity stress tolerance in bacteria has not
      heretofore been studied. This study provides an evidence for a novel function of
      the PDH45 gene in high salinity (NaCl) stress tolerance in bacteria (Eschericia
      coli, BL21 cells) also. Furthermore, it has been shown that the functionally
      active PDH45 gene is required to show the stress tolerance in bacteria because
      the single mutants (E183G or R363Q) and the double mutant (E183G + R363Q) of the
      gene could not confer the same function. The response was specific to Na+ ions as
      the bacteria could not grow in presence of LiCl. This study suggests that the
      cellular response to high salinity stress across prokaryotes and plant kingdom is
      conserved and also helps in our better understanding of mechanism of stress
      tolerance in bacteria and plants. It could also be very useful in developing high
      salinity stress tolerant useful bacteria of agronomic importance. Overall, this
      study provides an evidence for a novel function of the PDH45 gene in high
      salinity stress tolerance in bacteria.

PMID- 21847022
TI  - beta-expansins are divergently abundant in maize cultivars that contrast in their
      degree of salt resistance.
AB  - Zea mays L. exhibits a strong growth reduction in response to NaCl-induced stress
      that is attributable to a decline of cell division and elongation. Wall-loosening
      expansins are of major impact for cell wall extensibility and growth. This study
      provides an analysis of the impact of an 8-d 100 mM NaCl stress treatment on the
      mRNA abundance of the alpha-and beta-expansin sub-families using real-time
      quantitative RT-PCR. Moreover, we provide a comparative study of plants that
      contrast in their degree of salt resistance in order to reveal contrasting
      features of physiological functions that may bear a causal relation to the
      differential response of plants to salt. In result, the transcript abundance of
      wall-loosening beta-expansins was impaired in size-reduced leaves of the salt
      sensitive hybrid but not in leaves of the salt-resistant hybrid that maintained
      growth. This indicates a role for the beta-expansins in processes related to salt
      resistance.

PMID- 21847023
TI  - Molecular mechanism of crown root initiation and the different mechanisms between
      crown root and radicle in rice.
AB  - Monocot plants produce numerous adventitious (crown) roots. The plant hormone
      auxin has positive effects on crown root formation, while cytokinin suppresses
      it. We have demonstrated that auxin-induced CROWN ROOTLESS5 (CRL5) regulates
      crown root initiation in rice through the induction of OsRR1, a negative
      regulator of cytokinin signaling. CRL5 overexpressing calli formed adventitious
      roots, although CRL5 overexpressing plants did not induce ectopic roots,
      suggesting that CRL5, which promotes de novo root initiation, might function only
      in de-differentiated cells. A radicle initiated normally in a crl5 mutant, in
      spite of the defect in crown root initiation, whereas crown roots, but not a
      radicle, were produced in a radicleless1 (ral1) mutant. A crl5 ral1 double mutant
      displayed an additive phenotype, showing that the formation of each root is
      regulated by different genetic mechanisms in rice.

PMID- 21847024
TI  - The autophagy gene, ATG18a, plays a negative role in powdery mildew resistance
      and mildew-induced cell death in Arabidopsis.
AB  - Autophagy is a conserved intracellular recycling system that traffics cellular
      organelles and cytosolic proteins within lysosomes for reuse or breakdown in
      eukaryotes. Increased evidence indicates that autophagy is involved in programmed
      cell death and disease resistance in plants. We recently showed that atg2, atg5,
      atg7 and atg10 displayed early senescence and cell death in later growth stage
      under nutrient-rich conditions in Arabidopsis thaliana. These mutants also
      exhibited powdery mildew resistance and mildew-induced cell death. Salicylic acid
      (SA) signaling is required for atg2-mediated powdery mildew resistance, however,
      inactivation of SA signaling is not sufficient to fully suppress powdery mildew
      induced cell death in atg2 mutant1. Here, we show that atg18a-2 is also resistant
      to the powdery mildew pathogen, Golovinomyces cichoracearum, and it shows mildew
      induced cell death similar to the atg2 mutant. Taken together, our study reveals
      that autophagy plays important roles in suppression of cell death and defense
      response to the biotrophic pathogen, the powdery mildew fungus. Future work on
      autophagy in plants will shine light on how autophagy is involved in cell death
      and defense response in plants.

PMID- 21847026
TI  - Secondary wall NAC binding element (SNBE), a key cis-acting element required for
      target gene activation by secondary wall NAC master switches.
AB  - The biosynthesis of secondary walls in vascular plants requires the coordinated
      regulation of a suite of biosynthetic genes, and this coordination has recently
      been shown to be executed by the secondary wall NAC (SWN)-mediated
      transcriptional network. In Arabidopsis, five SWNs, including SND1, NST1/2 and
      VND6/7, function as master transcriptional switches to activate their common
      targets and consequently the secondary wall biosynthetic program. A recent report
      by Zhong et al. revealed that SWNs bind to a common cis-acting element, namely
      secondary wall NAC binding element (SNBE), which is composed of an imperfect
      palindromic 19-bp consensus sequence, (T/A)NN(C/T)(T/C/G)TNNNNNNNA(A/C)GN(A/C/T)
      (A/T). Genome-wide analysis of direct targets of SWNs showed that SWNs directly
      activate the expression of not only many transcription factors but also a battery
      of genes involved in secondary wall biosynthesis, cell wall modification and
      programmed cell death, the promoters of which all contain multiple SNBE sites.
      The functional significance of the SNBE sites is further substantiated by our
      current in planta expression study demonstrating that representative SNBE
      sequences from several SWN direct target promoters are sufficient to drive the
      expression of the GUS reporter gene in secondary wall-forming cells. The
      identification of the SWN DNA binding element (SNBE) and the SWN direct targets
      marks an important step forward toward the dissection of the transcriptional
      network regulating the biosynthesis of secondary walls, the most abundant biomass
      produced by land plants.

PMID- 21847025
TI  - Antimicrobial peptides: modes of mechanism, modulation of defense responses.
AB  - Complicated schemes of classical breeding and their drawbacks, environmental
      risks imposed by agrochemicals, decrease of arable land, and coincident
      escalating damages of pests and pathogens have accentuated the necessity for
      highly efficient measures to improve crop protection. During co-evolution of host
      microbe interactions, antimicrobial peptides (AMPs) have exhibited a brilliant
      history in protecting host organisms against devastation by invading pathogens.
      Since the 1980s, a plethora of AMPs has been isolated from and characterized in
      different organisms. Nevertheless the AMPs expressed in plants render them more
      resistant to diverse pathogens, a more orchestrated approach based on knowledge
      of their mechanisms of action and cellular targets, structural toxic principle,
      and possible impact on immune system of corresponding transgenic plants will
      considerably improve crop protection strategies against harmful plant diseases.
      This review outlines the current knowledge on different modes of action of AMPs
      and then argues the waves of AMPs' ectopic expression on transgenic plants'
      immune system.

PMID- 21847027
TI  - Beyond flowering time: pleiotropic function of the maize flowering hormone
      florigen.
AB  - The transition from vegetative to reproductive development is a critical turning
      point in a plant's life cycle. It is now widely accepted that a leaf-borne
      signal, florigen, moves via the phloem from leaves to the shoot apical meristem
      to trigger its reprogramming to produce flowers. In part, the florigenic signal
      comprises a protein that belongs to the phosphatidylethanolamine-binding protein
      (PEBP) family that is present in all living organisms but displays diverse
      functions. The founding floral-promoting PEBP gene in Arabidopsis is FLOWERING
      LOCUS T (FT) whose functional homologs have been indentified in many flowering
      plants. We recently accumulated sufficient evidence to demonstrate the maize FT
      homolog ZCN8 has florigenic function. This task was particularly challenging due
      to the large number of FT-homologous genes in the maize genome. Here we show that
      ZCN8 function is more complex than simply regulating the floral transition. ZCN8
      appears to play a pleiotropic role in the regulation of generalized growth of
      vegetative and reproductive tissues.

PMID- 21847028
TI  - Control of stomatal aperture: a renaissance of the old guard.
AB  - Stomata, functionally specialized small pores on the surfaces of leaves, regulate
      the flow of gases in and out of plants. The pore is opened by an increase in
      osmotic pressure in the guard cells, resulting in the uptake of water. The
      subsequent increase in cell volume inflates the guard cell and culminates with
      the opening of the pore. Although guard cells can be regarded as one of the most
      thoroughly investigated cell types, our knowledge of the signaling pathways which
      regulate guard cell function remains fragmented. Recent research in guard cells
      has led to several new hypotheses, however, it is still a matter of debate as to
      whether guard cells function autonomously or are subject to regulation by their
      neighboring mesophyll cells.This review synthesizes what is known about the
      mechanisms and genes critical for modulating stomatal movement. Recent progress
      on the regulation of guard cell function is reviewed here including the
      involvement of environmental signals such as light, the concentration of
      atmospheric CO2 and endogenous plant hormones. In addition we re-evaluate the
      important role of organic acids such as malate and fumarate play in guard cell
      metabolism in this process.

PMID- 21847029
TI  - Boolean function applied to Mimosa pudica movements.
AB  - Seismonastic or thigmonastic movements of Mimosa pudica L. is mostly because of
      the fast loss of water from swollen motor cells, resulting in temporary collapse
      of cells and quick curvature in the parts where these cells are located. Because
      of this, the plant has been much studied since the 18th century, leading us to
      think about the classical binomial stimulus-response (action-reaction) when
      compared to animals. Mechanic and electrical stimuli were used to investigate the
      analogy of mimosa branch with an artificial neuron model and to observe the
      action potential propagation through the mimosa branch. Boolean function applied
      to the mimosa branch in analogy with an artificial neuron model is one of the
      peculiarities of our hypothesis.

PMID- 21847030
TI  - Early signaling in actinorhizal symbioses.
AB  - Nitrogen-fixing root nodulation, confined to four plant orders, encompasses more
      than 14,000 Leguminosae species, and approximately 200 actinorhizal species
      forming symbioses with rhizobia (Rhizobium, Bradyrhizobium, etc) and Frankia
      bacterial species, respectively. While several genetic components of the host
      symbiont interaction have been identified in legumes, little is known about the
      genetic bases of actinorhizal symbiosis. However, we recently demonstrated the
      existence of common symbiotic signaling pathways in actinorhizals and legumes.
      Moreover, important data on the identification of flavonoids as plant signaling
      compounds and the role for auxins during Frankia infection process and nodule
      organogenesis have been acquired. All together these results lead us to propose a
      unified model for symbiotic exchange and genetic control of actinorhizal
      symbiosis.

PMID- 21847031
TI  - Responses of root hair development to elevated CO2.
AB  - This review highlights a potential signaling pathway of CO2-dependent stimulation
      in root hair development. Elevated CO2 firstly increases the carbohydrates
      production, which triggers the auxin or ethylene responsive signal transduction
      pathways and subsequently stimulates the generation of intracellular nitric oxide
      (NO). The NO acts on target Ca2+ and ion channels and induces activation of MAPK.
      Meanwhile, reactive oxygen species (ROS) activates cytoplasmic Ca2+ channels at
      the plasma membrane in the apex of the root tip. This complex pathway involves
      transduction cascades of multiple signals that lead to the fine tuning of
      epidermal cell initiation and elongation. The results suggest that elevated CO2
      plays an important role in cell differentiation processes at the root epidermis.

PMID- 21847032
TI  - Body magnetic resonance imaging at 3 T.

PMID- 21847033
TI  - Current problems and future opportunities of abdominal magnetic resonance imaging
      at higher field strengths.
AB  - Introduction of high-field-strength whole-body MR scanners to clinical routine
      made abdominal magnetic resonance (MR) imaging widely available. Higher field
      strength provides improved signal yield, but other issues such as shorter
      wavelength and increased power deposition of radiofrequency in tissue must also
      be taken into account. This review describes current problems and future
      opportunities of abdominal MR imaging at 3.0 T under special consideration of
      relevant physical properties and technical challenges: impact of higher field
      strength on signal-to-noise ratio, Larmor frequency, and chemical shift effects
      are elucidated in detail. Furthermore, changes in longitudinal and transverse
      relaxation times as well as increased susceptibility effects at 3.0 T are
      reported. General safety issues and limitations in radiofrequency power
      deposition are discussed. Subsequently, implications of the previously mentioned
      changed MR properties at 3.0 T on clinical abdominal examinations applying
      different sequence types are described.

PMID- 21847034
TI  - Abdominal magnetic resonance imaging at 3 T: oncological applications.
AB  - The gain in signal-to-noise ratio at 3 T magnetic resonance (MR) imaging produces
      many benefits for abdominal imaging applications, including the capability to
      reduce acquisition times and/or improve spatial resolution for a variety of pulse
      sequences, the potential for broader application of parallel imaging techniques,
      and an increased sensitivity to gadolinium-based contrast media. These advances
      have the potential of improving the accuracy of MR imaging in the detection,
      staging, treatment planning, and follow-up of patients with abdominal tumors. At
      the same time, because certain high-field-strength-related drawbacks could not be
      compensated for, abdominal 3 T MR imaging should be clinically implemented with
      caution in some patients (eg, patients with massive ascites).

PMID- 21847035
TI  - Renal and perfusion imaging at 3 T.
AB  - Magnetic resonance imaging is frequently used in the workup of various renal
      pathologies. In daily clinical practice, these studies are mainly performed on
      1.5-T magnetic resonance systems. However, the potential benefits of going to
      higher field strengths include higher signal-to-noise ratios, faster imaging, and
      better spatial resolution. As of now, few studies have been performed in the
      kidneys at 3 T because of the limited availability and the prevalence of signal
      voids, susceptibility artifacts, incomplete fat suppression, and specific
      absorption rate problems. In the last couple of years, however, a number of
      technical advances have been made to overcome these problems and allow renal
      imaging to be performed at 3 T. This review article aimed to provide an overview
      of the current clinical status of renal imaging at 3 T. We will discuss both
      anatomical and functional imaging of the kidneys, with some special focus on
      perfusion imaging.

PMID- 21847036
TI  - Benefits and challenges in bowel MR imaging at 3.0 T.
AB  - Abdominal imaging at 3.0 T has shown to be challenging because of a number of
      artifacts and effects related to the physics at higher field strength. For bowel
      imaging at 3.0 T, artifacts due to magnetic field inhomogeneities, standing
      waves, increased susceptibility, and greater chemical shift effects are of
      particular concern because they are likely to affect the assessment of relevant
      structures and counterbalance the benefits of higher signal-to-noise ratio.
      Regarding small- and large-bowel magnetic resonance imaging, the benefits of
      higher field strengths translate mainly in better contrast-to-noise ratio of
      contrast-enhanced T1-weighted gradient echo and T2-weighted imaging, whereas
      steady-state free precession sequences seem to suffer from serious degradation of
      image quality. The present article summarizes the technical challenges in bowel
      imaging at 3.0 T, provides an overview of performance compared with 1.5 T in
      small- and large-bowel diseases including the rectum, and revises the current
      literature.

PMID- 21847037
TI  - High-field magnetic resonance imaging of the pelvis: uterus, ovary, and prostate
      gland.
AB  - Today, magnetic resonance imaging (MRI) is a standard imaging modality for
      various pathologic disorders in the human pelvis. It has given proof of its
      usefulness in the diagnosis of several benign and malignant disorders, and it is
      routinely used for the local staging of different tumors even when confined to
      specific parts of a pelvic organ. Signal-to-noise ratio and motion artifacts of
      the examined organ and adjacent bowel structures are major factors for image
      quality. Setting at 3 T with surface coils avoids technical limitations and
      discomfort of additional endovaginal or endorectal coils. Definition of high
      field seems fuzzy because of the availability of MRI machines with 3, 7 T, or
      higher; therefore, the general aspects of MRI of pelvic structures with emphasis
      on uterus, ovary, and prostate gland and attention to promising newer techniques
      such as 3 T, dynamic contrast imaging, and diffusion-weighted imaging are
      reviewed in this article.

PMID- 21847038
TI  - Magnetic resonance angiography of abdominal vessels at 3 T.
AB  - Magnetic resonance angiography (MRA) has evolved significantly since first
      described in the early 1990s. Unrivaled image quality and freedom from artifacts
      has made it a reliable and widely utilized technique. Imaging at 3 T offers the
      potential for higher resolutions images with better temporal resolution compared
      to 1.5 T. This article will review the technique and contrast agents required to
      perform MRA at 3 T and the relevant clinical applications. We also discuss non
      contrast enhanced MRA in the era of nephrogenic systemic fibrosis and future
      prospect for MRA at 3 T.

PMID- 21847039
TI  - Erlotinib accumulation in brain metastases from non-small cell lung cancer:
      visualization by positron emission tomography in a patient harboring a mutation
      in the epidermal growth factor receptor.

PMID- 21847040
TI  - Using laser Raman spectroscopy to reduce false positives of autofluorescence
      bronchoscopies: a pilot study.
AB  - INTRODUCTION: Preneoplastic lesions of the bronchial tree have a high probability
      of developing into malignant tumors. Currently, the best method for localizing
      them for further treatment is a combined white light bronchoscopy (WLB) and
      autofluorescence bronchoscopy (AFB) (WLB + AFB). The average specificity from
      large clinical trials for this combined detection method is approximately 60%,
      leading to many false positives. The object of this study is to determine whether
      adding point laser Raman spectroscopy (LRS) to a WLB + AFB has the potential to
      improve the specificity of preneoplastic lesion detection and what the
      implication is to the detection sensitivity. METHODS: An LRS system was developed
      to collect real-time, in vivo lung spectra with a fiber optic catheter passed
      down the instrument channel of a bronchoscope. WLB + AFB imaging modalities were
      used to identify lesions from 26 subjects, from which 129 Raman spectra were
      measured. Multivariate statistical analyses were performed on the spectra with a
      leave-one-out crossvalidation. RESULTS: Clear in vivo Raman spectra were obtained
      in 1 second. The location of individual Raman peaks in the spectra correlated
      well with the known positions of Raman peaks generated by lipids, proteins, and
      water molecules. Preneoplastic lesions were detected with a sensitivity of 96%
      and a specificity of 91%. CONCLUSION: Adding point LRS analysis to WLB + AFB
      imaging has the ability to detect preneoplastic lesions in real time with high
      sensitivity and specificity. The use of LRS has great potential for substantially
      reducing the number of false-positive biopsies associated with WLB + AFB with
      very little reduction in the detection sensitivity.

PMID- 21847041
TI  - Erlotinib accumulation in brain metastases from non-small cell lung cancer:
      visualization by positron emission tomography in a patient harboring a mutation
      in the epidermal growth factor receptor.
AB  - INTRODUCTION: Drugs directed toward the epidermal growth factor receptor (EGFR),
      such as erlotinib (Tarceva(r)) and gefitinib (Iressa(r)), are used for the
      treatment of patients with advanced non-small cell lung cancer (NSCLC), including
      patients with brain metastases. However, whether erlotinib actually enters into
      brain metastases has not been adequately elucidated. In this study, we
      investigated the accumulation of [11C]-erlotinib by positron emission tomography
      (PET) combined with computed tomography (CT) and magnetic resonance imaging
      (MRI). METHODS: A 32-year-old patient with NSCLC and multiple brain metastases
      was treated with first-line erlotinib. EGFR mutations were determined by
      analyzing a fine-needle lung tumor biopsy taken before the treatment. A PET/CT of
      the brain with [11C]-erlotinib was performed during treatment, and a MRI of the
      head and a CT of the chest were performed pre- and posttreatment. RESULTS: The
      primary lung tumor displayed an erlotinib-sensitizing exon 19 deletion in the
      EGFR gene, and [11C]-erlotinib PET/CT showed accumulation in the brain
      metastases. Posttreatment MRI and CT demonstrated regression of both brain
      metastases and primary lung tumor. CONCLUSION: Our data demonstrated that
      erlotinib accumulated in brain metastases in a NSCLC patient who responded to the
      treatment.

PMID- 21847042
TI  - Glomus tumor of the trachea.
AB  - INTRODUCTION: We describe a primary glomus tumor of the trachea. METHODS: A
      patient presented to our institution with a mid-tracheal mass. RESULTS: We
      performed a tracheal resection on this patient. CONCLUSION: The final pathology
      was consistent with glomus tumor of the trachea.

PMID- 21847043
TI  - Late intravascular embolization of a chemo port catheter.

PMID- 21847045
TI  - A roundup of recently published articles relevant to thoracic oncology.
AB  - We selected six publications for the "best of the month," published recently in
      peer-reviewed journals, covering a broad range of topics including second-hand
      smoking, intensive care unit admissions for patients with lung cancer, role of
      aspirin in preventing lung cancer, bleeding events in patients undergoing
      treatment with bevacizumab and requiring full anticoagulation, level of evidence
      used to support the National Comprehensive Cancer Network guidelines, and the use
      of prophylactic cranial irradiation in patient with locally advanced non-small
      cell lung cancer.

PMID- 21847044
TI  - Pulmonary large cell carcinoma mimicking an infected thoracoabdominal aortic
      aneurysm.

PMID- 21847046
TI  - Classification of large cell neuroendocrine carcinoma: at the cross roads of
      small and non-small cell lung cancer.

PMID- 21847047
TI  - Switch maintenance versus second-line treatment in non-small cell lung cancer.

PMID- 21847048
TI  - Overview.

PMID- 21847049
TI  - Standard outcome measures for thymic malignancies.

PMID- 21847050
TI  - A review of prognostic factors in thymic malignancies.

PMID- 21847051
TI  - Bias, biostatistics, and prognostic factors.

PMID- 21847052
TI  - The Masaoka-Koga stage classification for thymic malignancies: clarification and
      definition of terms.

PMID- 21847053
TI  - Standard report terms for chest computed tomography reports of anterior
      mediastinal masses suspicious for thymoma.

PMID- 21847054
TI  - Policies and reporting guidelines for small biopsy specimens of mediastinal
      masses.

PMID- 21847055
TI  - Which way is up? Policies and procedures for surgeons and pathologists regarding
      resection specimens of thymic malignancy.

PMID- 21847056
TI  - Standard terms, definitions, and policies for minimally invasive resection of
      thymoma.

PMID- 21847057
TI  - Radiation therapy definitions and reporting guidelines for thymic malignancies.

PMID- 21847058
TI  - Chemotherapy definitions and policies for thymic malignancies.

PMID- 21847059
TI  - Systematic reviews and meta-analysis of published studies: an overview and best
      practices.
AB  - Systematic reviews and meta-analytic approaches are widely used in the clinical
      arena to integrate outcome data from published studies in a patient population
      that address a set of related research hypotheses. The credibility of this line
      of research is dependent on how the studies are chosen, how the data are
      assembled, and how the results are reported. In this brief report, we provide an
      overview of the minimum set of reporting requirements for systematic reviews and
      meta-analyses based on the Preferred Reporting Items of Systematic reviews and
      Meta-Analyses guidelines. As with any research, following a set of established
      guidelines is essential for quality and consistency of the findings across
      studies and for assessment of clinical utility.

PMID- 21847060
TI  - Recommendations for uniform definitions of surgical techniques for malignant
      pleural mesothelioma: a consensus report of the international association for the
      study of lung cancer international staging committee and the international
      mesothelioma interest group.
AB  - INTRODUCTION: Extrapleural pneumonectomy has been well defined; however, surgeons
      vary regarding the surgical extent and goals of "pleurectomy/decortication"
      (P/D). We explored mesothelioma surgeons' concepts of P/D with the aim of
      unifying surgical nomenclature. METHODS: A web-based survey was administered to
      surgeons who operated on malignant pleural mesothelioma (MPM) for diagnosis,
      staging, palliation, or cytoreduction. One hundred thirty surgeons from 59
      medical centers were included. Surgeons who did not perform surgery for MPM
      within the last year were excluded. RESULTS: There were 62 (48%) respondents from
      39 medical centers in 14 countries. The mean number of patients with MPM seen
      annually at each medical center was 46, and the mean annual number of
      cytoreductive procedures performed per surgeon was 8. Most (88%) agreed that the
      goal of cytoreductive surgery should be macroscopic complete resection of tumor.
      P/D was defined as resection of parietal and visceral pleura with the aim of
      achieving macroscopic complete resection by 72% of respondents. If the diaphragm
      or pericardium required resection, 64% preferred the term "radical P/D," whereas
      "P/D" (40%) or "total pleurectomy" (39%) was preferred if these structures were
      not removed. Most surgeons believed that extrapleural pneumonectomy (90%) or
      "radical P/D" (68%) could provide adequate cytoreduction, whereas only 23%
      thought that P/D could. CONCLUSIONS: There was significant variation regarding
      surgical nomenclature for procedures for MPM. The International Staging Committee
      of the International Association for the Study of Lung Cancer and the
      International Mesothelioma Interest Group recommend that P/D should aim to remove
      all macroscopic tumor involving the parietal and visceral pleura and should be
      termed "extended" P/D when the diaphragm or pericardium is resected.

PMID- 21847061
TI  - Analysis of tumor markers in the cytological fluid obtained from computed
      tomography-guided needle aspiration biopsy for the diagnosis of non-small cell
      lung cancer.
AB  - PURPOSE: The aim of this study was to prospectively assess whether analysis of
      the tumor markers cytokeratin 19 fragments (CYFRA 21-1), carcinoembryonic antigen
      (CEA), and squamous cell carcinoma (SCC) antigen in cytological fluid can improve
      the performance of computed tomography (CT)-guided needle aspiration biopsy (NAB)
      in the diagnosis of non-small cell lung cancer (NSCLC). METHODS: A total of 100
      patients (men:women = 41:59, mean age: 63 years) with suspected malignant
      pulmonary lesions were prospectively enrolled for CT-guided NAB procedures.
      Levels of CYFRA 21-1, CEA, and SCC in the cytological fluid were measured by
      immunoradiometric assays. The cutoff value for tumor markers was selected on the
      basis of best accuracy through receiver operating characteristic curves. The
      sensitivity and areas under the curve (AUC) of NAB alone were compared with those
      of NAB combined with cytological tumor markers (CYFRA 21-1, CEA, and SCC).
      RESULTS: Among 100 patients, 71 (71%) had NSCLC and 29 (29%) had benign lesions.
      The sensitivity, specificity, and accuracy for diagnosing NSCLC were 85.7%, 100%,
      and 89%, respectively, for NAB alone. The sensitivity increased significantly for
      NAB combined with a tumor marker compared with NAB alone (100% for CYFRA 21-1,
      92.9% for CEA, and 94.2% for SCC; p = 0.001, p = 0.025, and p = 0.014,
      respectively). The AUC of NAB with CYFRA 21-1 was significantly larger than the
      AUC of NAB alone (p = 0.001). CONCLUSION: Evaluation of tumor markers CYFRA 21-1,
      CEA, and SCC in the cytological fluid can improve the diagnostic performance of
      CT-guided NAB for NSCLC. Of these markers, CYFRA 21-1 is the most useful
      cytological tumor marker.

PMID- 21847062
TI  - Pathologic response after neoadjuvant carboplatin and weekly paclitaxel for early
      stage lung cancer: a Brown University oncology group phase II study.
AB  - INTRODUCTION: Pathologic complete response (pCR) to neoadjuvant chemotherapy is
      associated with improved survival in solid tumors. Southwest Oncology Group 9,900
      demonstrated a 9% pCR after three cycles of paclitaxel/carboplatin every 21 days.
      We evaluated pCR rate with intensive weekly paclitaxel in a phase II study.
      METHODS: Patients with non-small cell lung cancer, stage IB to IIIA, were
      eligible and received carboplatin, area under the curve = 6, every 21 days *3 and
      paclitaxel 80 mg/m weekly *9. Primary outcome was the pCR rate. RESULTS: Twenty
      patients with clinical stage IB (n = 16), IIA (n = 1), IIB (n = 1), and IIIA (n =
      2) were enrolled. Mean age was 65 years. Toxicity included grade 4 neutropenia in
      1 (5%), grade 3 neutropenia in 3 (15%), grade 3 neuropathy in 1 (5%), and grade 3
      nausea in 1 (5%). After neoadjuvant therapy, one patient refused surgery and one
      died of a nontreatment-related event. Eighteen patients underwent complete
      resection, 15 by lobectomy, and 3 by pneumonectomy. Pathology revealed 3 (17%)
      patients with pCR. The median follow-up is 67 months. For clinical stage IB (n =
      16), the median overall survival has not been reached, and the 5-year overall
      survival is 69%. All patients with pCR (n = 3) remain alive and disease-free.
      Improved overall survival was seen in patients who were pathologically down
      staged versus patients who were not, p = 0.05. CONCLUSIONS: Neoadjuvant
      chemotherapy with intensive weekly paclitaxel and carboplatin is well tolerated
      and does not increase surgical morbidity. This intense regimen achieves rates of
      pCR and survival that compares favorably with other reported induction regimens
      and merits further investigation.

PMID- 21847063
TI  - A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS
      mutations.
AB  - INTRODUCTION: KRAS mutations are present in 30% of lung adenocarcinomas.
      Salirasib prevents Ras membrane binding thereby blocking the function of all Ras
      isoforms. This phase II study determined the activity of salirasib in patients
      with advanced lung adenocarcinomas with KRAS mutations. METHODS: Two cohorts of
      patients with stage IIIB/IV lung adenocarcinoma were eligible: patients with
      tumors with KRAS mutations who were previously treated with chemotherapy and
      patients receiving initial therapy who had >=15 pack-year smoking history.
      Salirasib was given orally from days 1 to 28 of a 35-day cycle. The primary end
      point was the rate of nonprogression at 10 weeks. RESULTS: Thirty-three patients
      were enrolled. Thirty patients had KRAS mutations (23 patients who were
      previously treated and 7/10 patients who had no prior therapy). Of the previously
      treated patients, 7 of 23 (30%) had stable disease at 10 weeks, and 4 of 10 (40%)
      previously untreated patients had stable disease at 10 weeks. No patient had a
      radiographic partial response (0% observed rate, 95% confidence interval 0-12%).
      The median overall survival was not reached (>9 months) for previously untreated
      patients and it was 15 months for patients who received prior chemotherapy.
      Diarrhea, nausea, and fatigue were the most common toxicities. CONCLUSIONS:
      Salirasib at the current dose and schedule has insufficient activity in the
      treatment of KRAS mutant lung adenocarcinoma to warrant further evaluation. The
      successful enrollment of 30 patients with tumors with KRAS mutant lung
      adenocarcinoma over 15 months at a single site demonstrates that drug trials
      directed at a KRAS-specific genotype in lung cancer are feasible.

PMID- 21847065
TI  - ALK translocation in non-small cell lung cancer with adenocarcinoma and squamous
      cell carcinoma markers.

PMID- 21847064
TI  - A rare complication of a CT-guided biopsy.

PMID- 21847066
TI  - Insulin-producing mediastinal teratoma in early pregnancy.

PMID- 21847067
TI  - Sublobar resection of ground glass opacity--great data, but can I have more?

PMID- 21847068
TI  - European respiratory society/american thoracic society/international association
      for the study of lung cancer international multidisciplinary classification of
      lung adenocarcinoma: state of the art.

PMID- 21847069
TI  - JCOG0201 defined "radiological early peripheral lung adenocarcinoma".

PMID- 21847070
TI  - Synthesis of new riminophenazines with pyrimidine and pyrazine substitution at
      the 2-N position.
AB  - New riminophenazines with pyrimidine and pyrazine substituents at the 2-position
      were successfully synthesized. The key step is the 2-N-arylation of
      riminophenazines with pyrimidine and pyrazine. The optimized reaction conditions
      involve the use of a Pd2(dba)3/DPPF/Cs2CO3/toluene combination.

PMID- 21847071
TI  - Antiviral properties of lactoferrin--a natural immunity molecule.
AB  - Lactoferrin, a multifunctional iron binding glycoprotein, plays an important role
      in immune regulation and defence mechanisms against bacteria, fungi and viruses.
      Lactoferrin's iron withholding ability is related to inhibition of microbial
      growth as well as to modulation of motility, aggregation and biofilm formation of
      pathogenic bacteria. Independently of iron binding capability, lactoferrin
      interacts with microbial, viral and cell surfaces thus inhibiting microbial and
      viral adhesion and entry into host cells. Lactoferrin can be considered not only
      a primary defense factor against mucosal infections, but also a polyvalent
      regulator which interacts in viral infectious processes. Its antiviral activity,
      demonstrated against both enveloped and naked viruses, lies in the early phase of
      infection, thus preventing entry of virus in the host cell. This activity is
      exerted by binding to heparan sulphate glycosaminoglycan cell receptors, or viral
      particles or both. Despite the antiviral effect of lactoferrin, widely
      demonstrated in vitro studies, few clinical trials have been carried out and the
      related mechanism of action is still under debate. The nuclear localization of
      lactoferrin in different epithelial human cells suggests that lactoferrin exerts
      its antiviral effect not only in the early phase of surface interaction virus
      cell, but also intracellularly. The capability of lactoferrin to exert a potent
      antiviral activity, through its binding to host cells and/or viral particles, and
      its nuclear localization strengthens the idea that lactoferrin is an important
      brick in the mucosal wall, effective against viral attacks and it could be
      usefully applied as novel strategy for treatment of viral infections.

PMID- 21847072
TI  - Synthesis and contractile activity of substituted 1,2,3,4
      tetrahydroisoquinolines.
AB  - A series of different 1-monosubstituted and 1,1-disubstituted 1,2,3,4-tetrahydro
      isoquinolines was synthesized in high yields from different ketoamides. We have
      developed a convenient method for the synthesis of disubstituted derivatives by
      interaction of ketoamides with organomagnesium compounds, followed by cyclization
      in the presence of catalytic amounts of p-toluenesulfonic acid (PTSA). A number
      of substituents at the C-1 in the isoquinoline skeleton were introduced varying
      either carboxylic acid or organomagnesium compound. Some of the obtained 1,1
      dialkyl-1,2,3,4-tetrahydro-isoquinolines possess contractile activity against
      guinea pig's gastric smooth muscle preparations.

PMID- 21847073
TI  - Rapid diagnosis of avian influenza virus in wild birds: use of a portable rRT-PCR
      and freeze-dried reagents in the field.
AB  - Wild birds have been implicated in the spread of highly pathogenic avian
      influenza (HPAI) of the H5N1 subtype, prompting surveillance along migratory
      flyways. Sampling of wild birds for avian influenza virus (AIV) is often
      conducted in remote regions, but results are often delayed because of the need to
      transport samples to a laboratory equipped for molecular testing. Real-time
      reverse transcriptase polymerase chain reaction (rRT-PCR) is a molecular
      technique that offers one of the most accurate and sensitive methods for
      diagnosis of AIV. The previously strict lab protocols needed for rRT-PCR are now
      being adapted for the field. Development of freeze-dried (lyophilized) reagents
      that do not require cold chain, with sensitivity at the level of wet reagents has
      brought on-site remote testing to a practical goal. Here we present a method for
      the rapid diagnosis of AIV in wild birds using an rRT-PCR unit (Ruggedized
      Advanced Pathogen Identification Device or RAPID, Idaho Technologies, Salt Lake
      City, UT) that employs lyophilized reagents (Influenza A Target 1 Taqman; ASAY
      ASY-0109, Idaho Technologies). The reagents contain all of the necessary
      components for testing at appropriate concentrations in a single tube: primers,
      probes, enzymes, buffers and internal positive controls, eliminating errors
      associated with improper storage or handling of wet reagents. The portable unit
      performs a screen for Influenza A by targeting the matrix gene and yields results
      in 2-3 hours. Genetic subtyping is also possible with H5 and H7 primer sets that
      target the hemagglutinin gene. The system is suitable for use on cloacal and
      oropharyngeal samples collected from wild birds, as demonstrated here on the
      migratory shorebird species, the western sandpiper (Calidrus mauri) captured in
      Northern California. Animal handling followed protocols approved by the Animal
      Care and Use Committee of the U.S. Geological Survey Western Ecological Research
      Center and permits of the U.S. Geological Survey Bird Banding Laboratory. The
      primary advantage of this technique is to expedite diagnosis of wild birds,
      increasing the chances of containing an outbreak in a remote location. On-site
      diagnosis would also prove useful for identifying and studying infected
      individuals in wild populations. The opportunity to collect information on host
      biology (immunological and physiological response to infection) and spatial
      ecology (migratory performance of infected birds) will provide insights into the
      extent to which wild birds can act as vectors for AIV over long distances.

PMID- 21847074
TI  - Avian influenza surveillance with FTA cards: field methods, biosafety, and
      transportation issues solved.
AB  - Avian Influenza Viruses (AIVs) infect many mammals, including humans(1). These
      AIVs are diverse in their natural hosts, harboring almost all possible viral
      subtypes(2). Human pandemics of flu originally stem from AIVs(3). Many fatal
      human cases during the H5N1 outbreaks in recent years were reported. Lately, a
      new AIV related strain swept through the human population, causing the 'swine flu
      epidemic'(4). Although human trading and transportation activity seems to be
      responsible for the spread of highly pathogenic strains(5), dispersal can also
      partly be attributed to wild birds(6, 7). However, the actual reservoir of all
      AIV strains is wild birds. In reaction to this and in face of severe commercial
      losses in the poultry industry, large surveillance programs have been implemented
      globally to collect information on the ecology of AIVs, and to install early
      warning systems to detect certain highly pathogenic strains(8-12). Traditional
      virological methods require viruses to be intact and cultivated before analysis.
      This necessitates strict cold chains with deep freezers and heavy biosafety
      procedures to be in place during transport. Long-term surveillance is therefore
      usually restricted to a few field stations close to well equipped laboratories.
      Remote areas cannot be sampled unless logistically cumbersome procedures are
      implemented. These problems have been recognised(13, 14) and the use of
      alternative storage and transport strategies investigated (alcohols or
      guanidine)(15-17). Recently, Kraus et al.(18) introduced a method to collect,
      store and transport AIV samples, based on a special filter paper. FTA cards(19)
      preserve RNA on a dry storage basis(20) and render pathogens inactive upon
      contact(21). This study showed that FTA cards can be used to detect AIV RNA in
      reverse-transcription PCR and that the resulting cDNA could be sequenced and
      virus genes and determined. In the study of Kraus et al.(18) a laboratory isolate
      of AIV was used, and samples were handled individually. In the extension
      presented here, faecal samples from wild birds from the duck trap at the Ottenby
      Bird Observatory (SE Sweden) were tested directly to illustrate the usefulness of
      the methods under field conditions. Catching of ducks and sample collection by
      cloacal swabs is demonstrated. The current protocol includes up-scaling of the
      work flow from single tube handling to a 96-well design. Although less sensitive
      than the traditional methods, the method of FTA cards provides an excellent
      supplement to large surveillance schemes. It allows collection and analysis of
      samples from anywhere in the world, without the need to maintaining a cool chain
      or safety regulations with respect to shipping of hazardous reagents, such as
      alcohol or guanidine.

PMID- 21847075
TI  - Long-term culture of human breast cancer specimens and their analysis using
      optical projection tomography.
AB  - Breast cancer is a leading cause of mortality in the Western world. It is well
      established that the spread of breast cancer, first locally and later distally,
      is a major factor in patient prognosis. Experimental systems of breast cancer
      rely on cell lines usually derived from primary tumours or pleural effusions. Two
      major obstacles hinder this research: (i) some known sub-types of breast cancers
      (notably poor prognosis luminal B tumours) are not represented within current
      line collections; (ii) the influence of the tumour microenvironment is not
      usually taken into account. We demonstrate a technique to culture primary breast
      cancer specimens of all sub-types. This is achieved by using three-dimensional
      (3D) culture system in which small pieces of tumour are embedded in soft rat
      collagen I cushions. Within 2-3 weeks, the tumour cells spread into the collagen
      and form various structures similar to those observed in human tumours1. Viable
      adipocytes, epithelial cells and fibroblasts within the original core were
      evident on histology. Malignant epithelial cells with squamoid morphology were
      demonstrated invading into the surrounding collagen. Nuclear pleomorphism was
      evident within these cells, along with mitotic figures and apoptotic bodies. We
      have employed Optical Projection Tomography (OPT), a 3D imaging technology, in
      order to quantify the extent of tumour spread in culture. We have used OPT to
      measure the bulk volume of the tumour culture, a parameter routinely measured
      during the neo-adjuvant treatment of breast cancer patients to assess response to
      drug therapy. Here, we present an opportunity to culture human breast tumours
      without sub-type bias and quantify the spread of those ex vivo. This method could
      be used in the future to quantify drug sensitivity in original tumour. This may
      provide a more predictive model than currently used cell lines.

PMID- 21847076
TI  - High throughput microRNA profiling: optimized multiplex qRT-PCR at nanoliter
      scale on the fluidigm dynamic arrayTM IFCs.
AB  - The broad involvement of miRNAs in critical processes underlying development,
      tissue homoeostasis and disease has led to a surging interest among the research
      and pharmaceutical communities. To study miRNAs, it is essential that the
      quantification of microRNA levels is accurate and robust. By comparing wild-type
      to small RNA deficient mouse embryonic stem cells (mESC), we revealed a lack of
      accuracy and robustness in previous published multiplex qRT-PCR techniques. Here,
      we describe an optimized method, including purifying away excessive primers from
      previous multiplex steps before singleplex real time detection, which
      dramatically increases the accuracy and robustness of the technique. Furthermore,
      we explain how performing the technique on a microfluidic chip at nanoliter
      volumes significantly reduces reagent costs and permits time effective high
      throughput miRNA expression profiling.

PMID- 21847077
TI  - The three-dimensional human skin reconstruct model: a tool to study normal skin
      and melanoma progression.
AB  - Most in vitro studies in experimental skin biology have been done in 2
      dimensional (2D) monocultures, while accumulating evidence suggests that cells
      behave differently when they are grown within a 3D extra-cellular matrix and also
      interact with other cells (1-5). Mouse models have been broadly utilized to study
      tissue morphogenesis in vivo. However mouse and human skin have significant
      differences in cellular architecture and physiology, which makes it difficult to
      extrapolate mouse studies to humans. Since melanocytes in mouse skin are mostly
      localized in hair follicles, they have distinct biological properties from those
      of humans, which locate primarily at the basal layer of the epidermis. The recent
      development of 3D human skin reconstruct models has enabled the field to
      investigate cell-matrix and cell-cell interactions between different cell types.
      The reconstructs consist of a "dermis" with fibroblasts embedded in a collagen I
      matrix, an "epidermis", which is comprised of stratified, differentiated
      keratinocytes and a functional basement membrane, which separates epidermis from
      dermis. Collagen provides scaffolding, nutrient delivery, and potential for cell
      to-cell interaction. The 3D skin models incorporating melanocytic cells
      recapitulate natural features of melanocyte homeostasis and melanoma progression
      in human skin. As in vivo, melanocytes in reconstructed skin are localized at the
      basement membrane interspersed with basal layer keratinocytes. Melanoma cells
      exhibit the same characteristics reflecting the original tumor stage (RGP, VGP
      and metastatic melanoma cells) in vivo. Recently, dermal stem cells have been
      identified in the human dermis (6). These multi-potent stem cells can migrate to
      the epidermis and differentiate to melanocytes.

PMID- 21847078
TI  - In vivo near infrared fluorescence (NIRF) intravascular molecular imaging of
      inflammatory plaque, a multimodal approach to imaging of atherosclerosis.
AB  - The vascular response to injury is a well-orchestrated inflammatory response
      triggered by the accumulation of macrophages within the vessel wall leading to an
      accumulation of lipid-laden intra-luminal plaque, smooth muscle cell
      proliferation and progressive narrowing of the vessel lumen. The formation of
      such vulnerable plaques prone to rupture underlies the majority of cases of acute
      myocardial infarction. The complex molecular and cellular inflammatory cascade is
      orchestrated by the recruitment of T lymphocytes and macrophages and their
      paracrine effects on endothelial and smooth muscle cells.(1) Molecular imaging in
      atherosclerosis has evolved into an important clinical and research tool that
      allows in vivo visualization of inflammation and other biological processes.
      Several recent examples demonstrate the ability to detect high-risk plaques in
      patients, and assess the effects of pharmacotherapeutics in atherosclerosis.(4)
      While a number of molecular imaging approaches (in particular MRI and PET) can
      image biological aspects of large vessels such as the carotid arteries, scant
      options exist for imaging of coronary arteries.(2) The advent of high-resolution
      optical imaging strategies, in particular near-infrared fluorescence (NIRF),
      coupled with activatable fluorescent probes, have enhanced sensitivity and led to
      the development of new intravascular strategies to improve biological imaging of
      human coronary atherosclerosis. Near infrared fluorescence (NIRF) molecular
      imaging utilizes excitation light with a defined band width (650-900 nm) as a
      source of photons that, when delivered to an optical contrast agent or
      fluorescent probe, emits fluorescence in the NIR window that can be detected
      using an appropriate emission filter and a high sensitivity charge-coupled
      camera. As opposed to visible light, NIR light penetrates deeply into tissue, is
      markedly less attenuated by endogenous photon absorbers such as hemoglobin, lipid
      and water, and enables high target-to-background ratios due to reduced
      autofluorescence in the NIR window. Imaging within the NIR 'window' can
      substantially improve the potential for in vivo imaging.(2,5) Inflammatory
      cysteine proteases have been well studied using activatable NIRF probes(10), and
      play important roles in atherogenesis. Via degradation of the extracellular
      matrix, cysteine proteases contribute importantly to the progression and
      complications of atherosclerosis(8). In particular, the cysteine protease,
      cathepsin B, is highly expressed and colocalizes with macrophages in experimental
      murine, rabbit, and human atheromata.(3,6,7) In addition, cathepsin B activity in
      plaques can be sensed in vivo utilizing a previously described 1-D intravascular
      near-infrared fluorescence technology(6), in conjunction with an injectable
      nanosensor agent that consists of a poly-lysine polymer backbone derivatized with
      multiple NIR fluorochromes (VM110/Prosense750, ex/em 750/780nm, VisEn Medical,
      Woburn, MA) that results in strong intramolecular quenching at baseline.(10)
      Following targeted enzymatic cleavage by cysteine proteases such as cathepsin B
      (known to colocalize with plaque macrophages), the fluorochromes separate,
      resulting in substantial amplification of the NIRF signal. Intravascular
      detection of NIR fluorescence signal by the utilized novel 2D intravascular NIRF
      catheter now enables high-resolution, geometrically accurate in vivo detection of
      cathepsin B activity in inflamed plaque. In vivo molecular imaging of
      atherosclerosis using catheter-based 2D NIRF imaging, as opposed to a prior 1-D
      spectroscopic approach,(6) is a novel and promising tool that utilizes augmented
      protease activity in macrophage-rich plaque to detect vascular
      inflammation.(11,12) The following research protocol describes the use of an
      intravascular 2-dimensional NIRF catheter to image and characterize plaque
      structure utilizing key aspects of plaque biology. It is a translatable platform
      that when integrated with existing clinical imaging technologies including
      angiography and intravascular ultrasound (IVUS), offers a unique and novel
      integrated multimodal molecular imaging technique that distinguishes inflammatory
      atheromata, and allows detection of intravascular NIRF signals in human-sized
      coronary arteries.

PMID- 21847079
TI  - Establishment and propagation of human retinoblastoma tumors in immune deficient
      mice.
AB  - Culturing retinoblastoma tumor cells in defined stem cell media gives rise to
      primary tumorspheres that can be grown and maintained for only a limited time.
      These cultured tumorspheres may exhibit markedly different cellular phenotypes
      when compared to the original tumors. Demonstration that cultured cells have the
      capability of forming new tumors is important to ensure that cultured cells model
      the biology of the original tumor. Here we present a protocol for propagating
      human retinoblastoma tumors in vivo using Rag2(-/-) immune deficient mice.
      Cultured human retinoblastoma tumorspheres of low passage or cells obtained from
      freshly harvested human retinoblastoma tumors injected directly into the vitreous
      cavity of murine eyes form tumors within 2-4 weeks. These tumors can be harvested
      and either further passaged into murine eyes in vivo or grown as tumorspheres in
      vitro. Propagation has been successfully carried out for at least three passages
      thus establishing a continuing source of human retinoblastoma tissue for further
      experimentation.

PMID- 21847080
TI  - Cryopreservation of preimplantation embryos of cattle, sheep, and goats.
AB  - Preimplantation embryos from cattle, sheep, and goats may be cryopreserved for
      short- or long-term storage. Preimplantation embryos consist predominantly of
      water, and the avoidance of intracellular ice crystal formation during the
      cryopreservation process is of paramount importance to maintain embryo viability.
      Embryos are placed into a hypertonic solution (1.4 - 1.5 M) of a cryoprotective
      agent (CPA) such as ethylene glycol (EG) or glycerol (GLYC) to create an osmotic
      gradient that facilitates cellular dehydration. After embryos reach osmotic
      equilibrium in the CPA solution, they are individually loaded in the hypertonic
      CPA solution into 0.25 ml plastic straws for freezing. Embryos are placed into a
      controlled rate freezer at a temperature of -6 degrees C. Ice crystal formation
      is induced in the CPA solution surrounding the embryo, and crystallization causes
      an increase in the concentration of CPA outside of the embryo, causing further
      cellular dehydration. Embryos are cooled at a rate of 0.5 degrees C/min, enabling
      further dehydration, to a temperature of -34 degrees C before being plunged into
      liquid nitrogen (-196 degrees C). Cryopreserved embryos must be thawed prior to
      transfer to a recipient (surrogate) female. Straws containing the embryos are
      removed from the liquid nitrogen dewar, held in room temperature air for 3 to 5
      sec, and placed into a 37 degrees C water bath for 25 to 30 sec. Embryos
      cryopreserved in GLYC are placed into a 1 M solution of sucrose for 10 min for
      removal of the CPA before transfer to a recipient (surrogate) female. Embryos
      cryopreserved in EG, however, may be directly transferred to the uterus of a
      recipient.

PMID- 21847081
TI  - Identification and analysis of mouse erythroid progenitors using the CD71/TER119
      flow-cytometric assay.
AB  - The study of erythropoiesis aims to understand how red cells are formed from
      earlier hematopoietic and erythroid progenitors. Specifically, the rate of red
      cell formation is regulated by the hormone erythropoietin (Epo), whose synthesis
      is triggered by tissue hypoxia. A threat to adequate tissue oxygenation results
      in a rapid increase in Epo, driving an increase in erythropoietic rate, a process
      known as the erythropoietic stress response. The resulting increase in the number
      of circulating red cells improves tissue oxygen delivery. An efficient
      erythropoietic stress response is therefore critical to the survival and recovery
      from physiological and pathological conditions such as high altitude, anemia,
      hemorrhage, chemotherapy or stem cell transplantation. The mouse is a key model
      for the study of erythropoiesis and its stress response. Mouse definitive (adult
      type) erythropoiesis takes place in the fetal liver between embryonic days 12.5
      and 15.5, in the neonatal spleen, and in adult spleen and bone marrow. Classical
      methods of identifying erythroid progenitors in tissue rely on the ability of
      these cells to give rise to red cell colonies when plated in Epo-containing semi
      solid media. Their erythroid precursor progeny are identified based on
      morphological criteria. Neither of these classical methods allow access to large
      numbers of differentiation-stage-specific erythroid cells for molecular study.
      Here we present a flow-cytometric method of identifying and studying
      differentiation-stage-specific erythroid progenitors and precursors, directly in
      the context of freshly isolated mouse tissue. The assay relies on the cell
      surface markers CD71, Ter119, and on the flow-cytometric 'forward-scatter'
      parameter, which is a function of cell size. The CD71/Ter119 assay can be used to
      study erythroid progenitors during their response to erythropoietic stress in
      vivo, for example, in anemic mice or mice housed in low oxygen conditions. It may
      also be used to study erythroid progenitors directly in the tissues of
      genetically modified adult mice or embryos, in order to assess the specific role
      of the modified molecular pathway in erythropoiesis.

PMID- 21847082
TI  - FSL constructs: a simple method for modifying cell/virion surfaces with a range
      of biological markers without affecting their viability.
AB  - The ability to modify/visualize biological surfaces, and then study the modified
      cell/virion in a range of in vitro and in vivo environments is essential to
      gaining further insight into the function of specific molecules or the entire
      entity. Studies of biological surface modification are generally limited to
      genetic engineering of the organism or the covalent attachment of chemical
      moieties to the cell surface(1,2). However these traditional techniques expose
      the cell to chemical reactants, or they require significant manipulation to
      achieve the desired outcome, making them cumbersome, and they may also
      inadvertently affect the viability/functionality of the modified cell. A simple
      method to harmlessly modify the surface of cells is required. Recently a new
      technology, KODE Technology has introduced a range of novel constructs consisting
      of three components: a functional head group (F), a spacer (S) and a lipid tail
      (L) and are known as Function-Spacer-Lipid or FSL constructs3. The spacer (S) is
      selected to provide a construct that is dispersible in water, yet will
      spontaneously and stably incorporate into a membrane. FSL construct functional
      moieties (F) so far include a range of saccharides including blood group-related
      determinants, sialic acids, hyaluronan polysaccharides, fluorophores, biotin,
      radiolabels, and a range of peptides(3-12). FSL constructs have been used in
      modifying embryos, spermatozoa, zebrafish, epithelial/endometrial cells, red
      blood cells, and virions to create quality controls systems and diagnostic
      panels, to modify cell adhesion/ interaction/ separation/ immobilization, and for
      in vitro and in vivo imaging of cells/virions(3-12). The process of modifying
      cells/virions is generic and extremely simple. The most common procedure is
      incubation of cells (in lipid free media) with a solution for FSL constructs for
      1-2 hours at 37 degrees C(4-10). During the incubation the FSL constructs
      spontaneously incorporate into the membrane, and the process is complete. Washing
      is optional. Cells modified by FSL constructs are known as kodecytes(6-9), while
      virions are kodevirions(10). FSL constructs as direct infusions and
      kodecytes/kodevirions have been used in experimental animal models(7,8,10). All
      kodecytes/kodevirions appear to retain their normal vitality and functionality
      while gaining the new function of the F moiety(7,8,10,11). The combination of
      dispersibility in biocompatible media, spontaneous incorporation into cell
      membranes, and apparent low toxicity, makes FSL constructs valuable research
      tools for the study of cells and virions.

PMID- 21847083
TI  - Multiplex PCR and reverse line blot hybridization assay (mPCR/RLB).
AB  - Multiplex PCR/Reverse Line Blot Hybridization assay allows the detection of up to
      43 molecular targets in 43 samples using one multiplex PCR reaction followed by
      probe hybridization on a nylon membrane, which is re-usable. Probes are 5' amine
      modified to allow fixation to the membrane. Primers are 5' biotin modified which
      allows detection of hybridized PCR products using streptavidin-peroxidase and a
      chemiluminescent substrate via photosensitive film. With low setup and consumable
      costs, this technique is inexpensive (approximately US$2 per sample), high
      throughput (multiple membranes can be processed simultaneously) and has a short
      turnaround time (approximately 10 hours). The technique can be utilized in a
      number of ways. Multiple probes can be designed to detect sequence variation
      within a single amplified product, or multiple products can be amplified
      simultaneously, with one (or more) probes used for subsequent detection. A
      combination of both approaches can also be used within a single assay. The
      ability to include multiple probes for a single target sequence makes the assay
      highly specific. Published applications of mPCR/RLB include detection of
      antibiotic resistance genes(1,2), typing of methicillin-resistant Staphylococcus
      aureus(3-5) and Salmonella sp(6), molecular serotyping of Streptococcus
      pneumoniae(7,8), Streptococcus agalactiae(9) and enteroviruses(10,11),
      identification of Mycobacterium sp(12), detection of genital(13-15) and
      respiratory tract(16) and other(17) pathogens and detection and identification of
      mollicutes(18). However, the versatility of the technique means the applications
      are virtually limitless and not restricted to molecular analysis of micro
      organisms. The five steps in mPCR/RLB are a) Primer and Probe design, b) DNA
      extraction and PCR amplification c) Preparation of the membrane, d) Hybridization
      and detection, and e) Regeneration of the Membrane.

PMID- 21847084
TI  - Diagnostic necropsy and selected tissue and sample collection in rats and mice.
AB  - There are multiple sample types that may be collected from a euthanized animal in
      order to help diagnose or discover infectious agents in an animal colony. Proper
      collection of tissues for further histological processing can impact the quality
      of testing results. This article describes the conduct of a basic gross
      examination including identification of heart, liver, lungs, kidneys, and spleen,
      as well as how to collect those organs. Additionally four of the more difficult
      tissue/sample collection techniques are demonstrated. Lung collection and
      perfusion can be particularly challenging as the tissue needs to be properly
      inflated with a fixative in order for inside of the tissue to fix properly and to
      enable thorough histologic evaluation. This article demonstrates the step by step
      technique to remove the lung and inflate it with fixative in order to achieve
      optimal fixation of the tissue within 24 hours. Brain collection can be similarly
      challenging as the tissue is soft and easily damaged. This article demonstrates
      the step by step technique to expose and remove the brain from the skull with
      minimal damage to the tissue. The mesenteric lymph node is a good sample type in
      which to detect many common infectious agents as enteric viruses persist longer
      in the lymph node than they are shed in feces. This article demonstrates the step
      by step procedure for locating and aseptically removing the mesenteric lymph
      node. Finally, identification of infectious agents of the respiratory tract may
      be performed by bacterial culture or PCR testing of nasal and/or bronchial fluid
      aspirates taken at necropsy. This procedure describes obtaining and preparing the
      respiratory aspirate sample for bacterial culture and PCR testing.

PMID- 21847086
TI  - Haptic/graphic rehabilitation: integrating a robot into a virtual environment
      library and applying it to stroke therapy.
AB  - Recent research that tests interactive devices for prolonged therapy practice has
      revealed new prospects for robotics combined with graphical and other forms of
      biofeedback. Previous human-robot interactive systems have required different
      software commands to be implemented for each robot leading to unnecessary
      developmental overhead time each time a new system becomes available. For
      example, when a haptic/graphic virtual reality environment has been coded for one
      specific robot to provide haptic feedback, that specific robot would not be able
      to be traded for another robot without recoding the program. However, recent
      efforts in the open source community have proposed a wrapper class approach that
      can elicit nearly identical responses regardless of the robot used. The result
      can lead researchers across the globe to perform similar experiments using shared
      code. Therefore modular "switching out"of one robot for another would not affect
      development time. In this paper, we outline the successful creation and
      implementation of a wrapper class for one robot into the open-source H3DAPI,
      which integrates the software commands most commonly used by all robots.

PMID- 21847085
TI  - Targeted training of ultrasonic vocalizations in aged and Parkinsonian rats.
AB  - Voice deficits are a common complication of both Parkinson disease (PD) and
      aging; they can significantly diminish quality of life by impacting communication
      abilities. (1, 2) Targeted training (speech/voice therapy) can improve specific
      voice deficits,(3, 4) although the underlying mechanisms of behavioral
      interventions are not well understood. Systematic investigation of voice deficits
      and therapy should consider many factors that are difficult to control in humans,
      such as age, home environment, age post-onset of disease, severity of disease,
      and medications. The method presented here uses an animal model of vocalization
      that allows for systematic study of how underlying sensorimotor mechanisms change
      with targeted voice training. The ultrasonic recording and analysis procedures
      outlined in this protocol are applicable to any investigation of rodent
      ultrasonic vocalizations. The ultrasonic vocalizations of rodents are emerging as
      a valuable model to investigate the neural substrates of behavior.(5-8) Both
      rodent and human vocalizations carry semiotic value and are produced by modifying
      an egressive airflow with a laryngeal constriction.(9, 10) Thus, rodent
      vocalizations may be a useful model to study voice deficits in a sensorimotor
      context. Further, rat models allow us to study the neurobiological underpinnings
      of recovery from deficits with targeted training. To model PD we use Long-Evans
      rats (Charles River Laboratories International, Inc.) and induce parkinsonism by
      a unilateral infusion of 7 MUg of 6-hydroxydopamine (6-OHDA) into the medial
      forebrain bundle which causes moderate to severe degeneration of presynaptic
      striatal neurons (for details see Ciucci, 2010).(11, 12) For our aging model we
      use the Fischer 344/Brown Norway F1 (National Institute on Aging). Our primary
      method for eliciting vocalizations is to expose sexually-experienced male rats to
      sexually receptive female rats. When the male becomes interested in the female,
      the female is removed and the male continues to vocalize. By rewarding complex
      vocalizations with food or water, both the number of complex vocalizations and
      the rate of vocalizations can be increased (Figure 1). An ultrasonic microphone
      mounted above the male's home cage records the vocalizations. Recording begins
      after the female rat is removed to isolate the male calls. Vocalizations can be
      viewed in real time for training or recorded and analyzed offline. By recording
      and acoustically analyzing vocalizations before and after vocal training, the
      effects of disease and restoration of normal function with training can be
      assessed. This model also allows us to relate the observed behavioral (vocal)
      improvements to changes in the brain and neuromuscular system.

PMID- 21847087
TI  - A cautionary note against 'one size fits all'.

PMID- 21847090
TI  - C/EBPbeta mediates tumour-induced ubiquitin ligase atrogin1/MAFbx upregulation
      and muscle wasting.
AB  - Upregulation of ubiquitin ligase atrogin1/MAFbx and muscle wasting are hallmarks
      of cancer cachexia; however, the underlying mechanism is undefined. Here, we
      describe a novel signalling pathway through which Lewis lung carcinoma (LLC)
      induces atrogin1/MAFbx upregulation and muscle wasting. C2C12 myotubes treated
      with LLC-conditioned medium (LCM) rapidly activates p38 MAPK and AKT while
      inactivating FoxO1/3, resulting in atrogin1/MAFbx upregulation, myosin heavy
      chain loss, and myotube atrophy. The p38alpha/beta MAPK inhibitor SB202190 blocks
      the catabolic effects. Upon activation, p38 associates with C/EBPbeta resulting
      in its phosphorylation and binding to a C/EBPbeta-responsive cis-element in the
      atrogin1/MAFbx gene promoter. The promoter activity is stimulated by LCM via
      p38beta-mediated activation of the C/EBPbeta-responsive cis-element, independent
      of the adjacent FoxO1/3-responsive cis-elements in the promoter. In addition, p38
      activation is observed in the muscle of LLC tumour-bearing mice, and SB202190
      administration blocks atrogin1/MAFbx upregulation and muscle protein loss.
      Furthermore, C/EBPbeta(-/-) mice are resistant to LLC tumour-induced
      atrogin1/MAFbx upregulation and muscle wasting. Therefore, activation of the
      p38beta MAPK-C/EBPbeta signalling pathway appears a key component of the
      pathogenesis of LLC tumour-induced cachexia.

PMID- 21847091
TI  - A thermodynamic switch modulates abscisic acid receptor sensitivity.
AB  - Abscisic acid (ABA) is a key hormone regulating plant growth, development and the
      response to biotic and abiotic stress. ABA binding to pyrabactin resistance
      (PYR)/PYR1-like (PYL)/Regulatory Component of Abscisic acid Receptor (RCAR)
      intracellular receptors promotes the formation of stable complexes with certain
      protein phosphatases type 2C (PP2Cs), leading to the activation of ABA
      signalling. The PYR/PYL/RCAR family contains 14 genes in Arabidopsis and is
      currently the largest plant hormone receptor family known; however, it is unclear
      what functional differentiation exists among receptors. Here, we identify two
      distinct classes of receptors, dimeric and monomeric, with different intrinsic
      affinities for ABA and whose differential properties are determined by the
      oligomeric state of their apo forms. Moreover, we find a residue in PYR1, H60,
      that is variable between family members and plays a key role in determining
      oligomeric state. In silico modelling of the ABA activation pathway reveals that
      monomeric receptors have a competitive advantage for binding to ABA and PP2Cs.
      This work illustrates how receptor oligomerization can modulate hormonal
      responses and more generally, the sensitivity of a ligand-dependent signalling
      system.

PMID- 21847092
TI  - An extended dsRBD with a novel zinc-binding motif mediates nuclear retention of
      fission yeast Dicer.
AB  - Dicer proteins function in RNA interference (RNAi) pathways by generating small
      RNAs (sRNAs). Here, we report the solution structure of the C-terminal domain of
      Schizosaccharomyces pombe Dicer (Dcr1). The structure reveals an unusual double
      stranded RNA binding domain (dsRBD) fold embedding a novel zinc-binding motif
      that is conserved among dicers in yeast. Although the C-terminal domain of Dcr1
      still binds nucleic acids, this property is dispensable for proper functioning of
      Dcr1. In contrast, disruption of zinc coordination renders Dcr1 mainly
      cytoplasmic and leads to remarkable changes in gene expression and loss of
      heterochromatin assembly. In summary, our results reveal novel insights into the
      mechanism of nuclear retention of Dcr1 and raise the possibility that this new
      class of dsRBDs might generally function in nucleocytoplasmic trafficking and not
      substrate binding. The C-terminal domain of Dcr1 constitutes a novel regulatory
      module that might represent a potential target for therapeutic intervention with
      fungal diseases.

PMID- 21847093
TI  - ERK7 is a negative regulator of protein secretion in response to amino-acid
      starvation by modulating Sec16 membrane association.
AB  - RNAi screening for kinases regulating the functional organization of the early
      secretory pathway in Drosophila S2 cells has identified the atypical Mitotic
      Associated Protein Kinase (MAPK) Extracellularly regulated kinase 7 (ERK7) as a
      new modulator. We found that ERK7 negatively regulates secretion in response to
      serum and amino-acid starvation, in both Drosophila and human cells. Under these
      conditions, ERK7 turnover through the proteasome is inhibited, and the resulting
      higher levels of this kinase lead to a modification in a site within the C
      terminus of Sec16, a key ER exit site component. This post-translational
      modification elicits the cytoplasmic dispersion of Sec16 and the consequent
      disassembly of the ER exit sites, which in turn results in protein secretion
      inhibition. We found that ER exit site disassembly upon starvation is TOR complex
      1 (TORC1) independent, showing that under nutrient stress conditions, cell growth
      is not only inhibited at the transcriptional and translational levels, but also
      independently at the level of secretion by inhibiting the membrane flow through
      the early secretory pathway. These results reveal the existence of new signalling
      circuits participating in the complex regulation of cell growth.

PMID- 21847094
TI  - Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by
      deacetylation of cortactin.
AB  - Histone deacetylases (HDACs) deacetylate histones and non-histone proteins,
      thereby affecting protein activity and gene expression. The regulation and
      function of the cytoplasmic class IIb HDAC6 in endothelial cells (ECs) is largely
      unexplored. Here, we demonstrate that HDAC6 is upregulated by hypoxia and is
      essential for angiogenesis. Silencing of HDAC6 in ECs decreases sprouting and
      migration in vitro and formation of functional vascular networks in matrigel
      plugs in vivo. HDAC6 regulates zebrafish vessel formation, and HDAC6-deficient
      mice showed a reduced formation of perfused vessels in matrigel plugs.
      Consistently, overexpression of wild-type HDAC6 increases sprouting from
      spheroids. HDAC6 function requires the catalytic activity but is independent of
      ubiquitin binding and deacetylation of alpha-tubulin. Instead, we found that
      HDAC6 interacts with and deacetylates the actin-remodelling protein cortactin in
      ECs, which is essential for zebrafish vessel formation and which mediates the
      angiogenic effect of HDAC6. In summary, we show that HDAC6 is necessary for
      angiogenesis in vivo and in vitro, involving the interaction and deacetylation of
      cortactin that regulates EC migration and sprouting.

PMID- 21847095
TI  - Calcium microdomains at the immunological synapse: how ORAI channels,
      mitochondria and calcium pumps generate local calcium signals for efficient T
      cell activation.
AB  - Cell polarization enables restriction of signalling into microdomains.
      Polarization of lymphocytes following formation of a mature immunological synapse
      (IS) is essential for calcium-dependent T-cell activation. Here, we analyse
      calcium microdomains at the IS with total internal reflection fluorescence
      microscopy. We find that the subplasmalemmal calcium signal following IS
      formation is sufficiently low to prevent calcium-dependent inactivation of ORAI
      channels. This is achieved by localizing mitochondria close to ORAI channels.
      Furthermore, we find that plasma membrane calcium ATPases (PMCAs) are re
      distributed into areas beneath mitochondria, which prevented PMCA up-modulation
      and decreased calcium export locally. This nano-scale distribution-only induced
      following IS formation-maximizes the efficiency of calcium influx through ORAI
      channels while it decreases calcium clearance by PMCA, resulting in a more
      sustained NFAT activity and subsequent activation of T cells.

PMID- 21847096
TI  - Pin1 and WWP2 regulate GluR2 Q/R site RNA editing by ADAR2 with opposing effects.
AB  - ADAR2 catalyses the deamination of adenosine to inosine at the GluR2 Q/R site in
      the pre-mRNA encoding the critical subunit of AMPA receptors. Among ADAR2
      substrates this is the vital one as editing at this position is indispensable for
      normal brain function. However, the regulation of ADAR2 post-translationally
      remains to be elucidated. We demonstrate that the phosphorylation-dependent
      prolyl-isomerase Pin1 interacts with ADAR2 and is a positive regulator required
      for the nuclear localization and stability of ADAR2. Pin1(-/-) mouse embryonic
      fibroblasts show mislocalization of ADAR2 in the cytoplasm and reduced editing at
      the GluR2 Q/R and R/G sites. The E3 ubiquitin ligase WWP2 plays a negative role
      by binding to ADAR2 and catalysing its ubiquitination and subsequent degradation.
      Therefore, ADAR2 protein levels and catalytic activity are coordinately regulated
      in a positive manner by Pin1 and negatively by WWP2 and this may have downstream
      effects on the function of GluR2. Pin1 and WWP2 also regulate the large subunit
      of RNA Pol II, so these proteins may also coordinately regulate other key
      cellular proteins.

PMID- 21847097
TI  - CBP is required for environmental enrichment-induced neurogenesis and cognitive
      enhancement.
AB  - The epigenetic changes of the chromatin represent an attractive molecular
      substrate for adaptation to the environment. We examined here the role of CREB
      binding protein (CBP), a histone acetyltransferase involved in mental
      retardation, in the genesis and maintenance of long-lasting systemic and
      behavioural adaptations to environmental enrichment (EE). Morphological and
      behavioural analyses demonstrated that EE ameliorates deficits associated to CBP
      deficiency. However, CBP-deficient mice also showed a strong defect in
      environment-induced neurogenesis and impaired EE-mediated enhancement of spatial
      navigation and pattern separation ability. These defects correlated with an
      attenuation of the transcriptional programme induced in response to EE and with
      deficits in histone acetylation at the promoters of EE-regulated, neurogenesis
      related genes. Additional experiments in CBP restricted and inducible knockout
      mice indicated that environment-induced adult neurogenesis is extrinsically
      regulated by CBP function in mature granule cells. Overall, our experiments
      demonstrate that the environment alters gene expression by impinging on
      activities involved in modifying the epigenome and identify CBP-dependent
      transcriptional neuroadaptation as an important mediator of EE-induced benefits,
      a finding with important implications for mental retardation therapeutics.

PMID- 21847098
TI  - PIKE-mediated PI3-kinase activity is required for AMPA receptor surface
      expression.
AB  - AMPAR (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor) is an
      ion channel involved in the formation of synaptic plasticity. However, the
      molecular mechanism that couples plasticity stimuli to the trafficking of
      postsynaptic AMPAR remains poorly understood. Here, we show that PIKE
      (phosphoinositide 3-kinase enhancer) GTPases regulate neuronal AMPAR activity by
      promoting GluA2/GRIP1 association. PIKE-L directly interacts with both GluA2 and
      GRIP1 and forms a tertiary complex upon glycine-induced NMDA receptor activation.
      PIKE-L is also essential for glycine-induced GluA2-associated PI3K activation.
      Genetic ablation of PIKE (PIKE(-/-)) in neurons suppresses GluA2-associated PI3K
      activation, therefore inhibiting the subsequent surface expression of GluA2 and
      the formation of long-term potentiation. Our findings suggest that PIKE-L is a
      critical factor in controlling synaptic AMPAR insertion.

PMID- 21847099
TI  - H3K4 tri-methylation provides an epigenetic signature of active enhancers.
AB  - Combinations of post-translational histone modifications shape the chromatin
      landscape during cell development in eukaryotes. However, little is known about
      the modifications exactly delineating functionally engaged regulatory elements.
      For example, although histone H3 lysine 4 mono-methylation (H3K4me1) indicates
      the presence of transcriptional gene enhancers, it does not provide clearcut
      information about their actual position and stage-specific activity. Histone
      marks were, therefore, studied here at genomic loci differentially expressed in
      early stages of T-lymphocyte development. The concomitant presence of the three
      H3K4 methylation states (H3K4me1/2/3) was found to clearly reflect the activity
      of bona fide T-cell gene enhancers. Globally, gain or loss of H3K4me2/3 at distal
      genomic regions correlated with, respectively, the induction or the repression of
      associated genes during T-cell development. In the Tcrb gene enhancer, the
      H3K4me3-to-H3K4me1 ratio decreases with the enhancer's strength. Lastly, enhancer
      association of RNA-polymerase II (Pol II) correlated with the presence of H3K4me3
      and Pol II accumulation resulted in local increase of H3K4me3. Our results
      suggest the existence of functional links between Pol II occupancy, H3K4me3
      enrichment and enhancer activity.

PMID- 21847100
TI  - Structural analysis of the Ras-like G protein MglA and its cognate GAP MglB and
      implications for bacterial polarity.
AB  - The bacterium Myxococcus xanthus uses a G protein cycle to dynamically regulate
      the leading/lagging pole polarity axis. The G protein MglA is regulated by its
      GTPase-activating protein (GAP) MglB, thus resembling Ras family proteins. Here,
      we show structurally and biochemically that MglA undergoes a dramatic, GDP-GTP
      dependent conformational change involving a screw-type forward movement of the
      central beta2-strand, never observed in any other G protein. This movement and
      complex formation with MglB repositions the conserved residues Arg53 and Gln82
      into the active site. Residues required for catalysis are thus not provided by
      the GAP MglB, but by MglA itself. MglB is a Roadblock/LC7 protein and functions
      as a dimer to stimulate GTP hydrolysis in a 2:1 complex with MglA. In vivo
      analyses demonstrate that hydrolysis mutants abrogate Myxococcus' ability to
      regulate its polarity axis changing the reversal behaviour from stochastic to
      oscillatory and that both MglA GTPase activity and MglB GAP catalysis are
      essential for maintaining a proper polarity axis.

PMID- 21847101
TI  - Erythropoietin gene-enhanced marrow mesenchymal stromal cells decrease cisplatin
      induced kidney injury and improve survival of allogeneic mice.
AB  - Bone marrow-derived mesenchymal stromal cells (MSCs) are promising for
      regenerative medicine applications, such as for renoprotection and repair in
      acute kidney injury (AKI). Erythropoietin (Epo) can also exert cytoprotective
      effects on various tissues including the kidney. We hypothesized that MSCs gene
      enhanced to secrete Epo may produce a significant beneficial effect in AKI. Mouse
      Epo-secreting MSCs were generated, tested in vitro, and then implanted by
      intraperitoneal injection in allogeneic mice previously administered cisplatin to
      induce AKI. Epo-MSCs significantly improved survival of implanted mice as
      compared to controls (67% survival versus 33% with Vehicle only). Also, Epo-MSCs
      led to significantly better kidney function as shown by lower levels of blood
      urea nitrogen (72 +/- 9.5 mg/dl versus 131 +/- 9.20 mg/dl) and creatinine (74 +/-
      17 umol/l versus 148+/-19.4 umol/l). Recipient mice also showed significantly
      decreased amylase and alanine aminotransferase blood concentrations. Kidney
      sections revealed significantly less apoptotic cells and more proliferating
      cells. Furthermore, PCR revealed the presence of implanted cells in recipient
      kidneys, with Epo-MSCs leading to significantly increased expression of Epo and
      of phosphorylated-Akt (Ser473) (P-Akt) in these kidneys. In conclusion, our study
      demonstrates that Epo gene-enhanced MSCs exert significant tissue protective
      effects in allogeneic mice with AKI, and supports the potential use of gene
      enhanced cells as universal donors in acute injury.

PMID- 21847102
TI  - Highly aligned carbon nanotube forests coated by superconducting NbC.
AB  - The formation of carbon nanotube and superconductor composites makes it possible
      to produce new and/or improved functionalities that the individual material does
      not possess. Here we show that coating carbon nanotube forests with
      superconducting niobium carbide (NbC) does not destroy the microstructure of the
      nanotubes. NbC also shows much improved superconducting properties such as a
      higher irreversibility and upper critical field. An upper critical field value of
      ~5 T at 4.2 K is much greater than the 1.7 T reported in the literature for pure
      bulk NbC. Furthermore, the aligned carbon nanotubes induce anisotropy in the
      upper critical field, with a higher upper critical field occurring when the
      magnetic field is parallel to the carbon nanotube growth direction. These results
      suggest that highly oriented carbon nanotubes embedded in superconducting NbC
      matrix can function as defects and effectively enhance the superconducting
      properties of the NbC.

PMID- 21847103
TI  - On-chip steering of entangled photons in nonlinear photonic crystals.
AB  - One promising technique for working toward practical photonic quantum
      technologies is to implement multiple operations on a monolithic chip, thereby
      improving stability, scalability and miniaturization. The on-chip spatial control
      of entangled photons will certainly benefit numerous applications, including
      quantum imaging, quantum lithography, quantum metrology and quantum computation.
      However, external optical elements are usually required to spatially control the
      entangled photons. Here we present the first experimental demonstration of on
      chip spatial control of entangled photons, based on a domain-engineered nonlinear
      photonic crystal. We manipulate the entangled photons using the inherent
      properties of the crystal during the parametric downconversion, demonstrating two
      photon focusing and beam-splitting from a periodically poled lithium tantalate
      crystal with a parabolic phase profile. These experimental results indicate that
      versatile and precise spatial control of entangled photons is achievable. Because
      they may be operated independent of any bulk optical elements, domain-engineered
      nonlinear photonic crystals may prove to be a valuable ingredient in on-chip
      integrated quantum optics.

PMID- 21847104
TI  - A CLASP-modulated cell edge barrier mechanism drives cell-wide cortical
      microtubule organization in Arabidopsis.
AB  - It is well known that the parallel order of microtubules in the plant cell cortex
      defines the direction of cell expansion, yet it remains unclear how microtubule
      orientation is controlled, especially on a cell-wide basis. Here we show through
      4D imaging and computational modelling that plant cell polyhedral geometry
      provides spatial input that determines array orientation and heterogeneity.
      Microtubules depolymerize when encountering sharp cell edges head-on, whereas
      those oriented parallel to those sharp edges remain. Edge-induced microtubule
      depolymerization, however, is overcome by the microtubule-associated protein
      CLASP, which accumulates at specific cell edges, enables microtubule growth
      around sharp edges and promotes formation of microtubule bundles that span
      adjacent cell faces. By computationally modelling dynamic 'microtubules on a
      cube' with edges differentially permissive to microtubule passage, we show that
      the CLASP-edge complex is a 'tuneable' microtubule organizer, with the inherent
      flexibility to generate the numerous cortical array patterns observed in nature.

PMID- 21847105
TI  - Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular
      mapping.
AB  - Graded expression of EphB and ephrin-B along the dorsoventral axis of the retina
      indicates a role for these bidirectional signalling molecules in dorsoventral
      mediolateral retinocollicular mapping. Although previous studies have implicated
      EphB2 forward signalling in mice, the intracellular component of EphB2 essential
      for retinocollicular mapping is unknown as are the roles for EphB1, ephrin-B1,
      and ephrin-B2. Here we show that EphB2 tyrosine kinase catalytic activity and
      EphB1 intracellular signalling are key mediators of ventral-temporal retinal
      ganglion cell axon retinocollicular mapping, by likely interacting with ephrin-B1
      in the superior colliculus. We further elucidate roles for the ephrin-B2
      intracellular domain in retinocollicular mapping and present the unexpected
      finding that both dorsal and ventral-temporal retinal ganglion cell axons utilize
      reverse signalling for topographic mapping. These data demonstrate that both
      forward and reverse signalling initiated by EphB:ephrin-B interactions have a
      major role in dorsoventral retinal ganglion cell axon termination along the
      mediolateral axis of the superior colliculus.

PMID- 21847106
TI  - Fermi-surface reconstruction by stripe order in cuprate superconductors.
AB  - The origin of pairing in a superconductor resides in the underlying normal state.
      In the cuprate high-temperature superconductor YBa(2)Cu(3)O(y) (YBCO),
      application of a magnetic field to suppress superconductivity reveals a ground
      state that appears to break the translational symmetry of the lattice, pointing
      to some density-wave order. Here we use a comparative study of thermoelectric
      transport in the cuprates YBCO and La(1.8-x)Eu(0.2)Sr(x)CuO(4) (Eu-LSCO) to show
      that the two materials exhibit the same process of Fermi-surface reconstruction
      as a function of temperature and doping. The fact that in Eu-LSCO this
      reconstruction coexists with spin and charge modulations that break translational
      symmetry shows that stripe order is the generic non-superconducting ground state
      of hole-doped cuprates.

PMID- 21847107
TI  - SIRT6 is required for maintenance of telomere position effect in human cells.
AB  - In Saccharomyces cerevisiae, the repressive chromatin environment at telomeres
      gives rise to telomere position effect (TPE), the epigenetic silencing of
      telomere-proximal genes. Chromatin-modifying factors that control TPE in yeast
      have been extensively studied, and, among these, the lifespan regulator and
      silencing protein Sir2 has a pivotal role. In contrast, the factors that generate
      and maintain silent telomeric chromatin in human cells remain largely unknown.
      Here we show that the Sir2 family member SIRT6 is required for maintenance of TPE
      in human cells. RNAi-mediated depletion of SIRT6 abrogates silencing of both an
      integrated telomeric transgene and an endogenous telomere-proximal gene.
      Moreover, enhanced telomeric silencing in response to telomere elongation is
      associated with increased repressive chromatin marks, and this heterochromatic
      milieu is lost in SIRT6-deficient cells. Together, these findings establish a new
      role for SIRT6 in regulating an ageing-associated epigenetic silencing process
      and provide new mechanistic insight into chromatin silencing at telomeres.

PMID- 21847108
TI  - The evolution of antisocial punishment in optional public goods games.
AB  - Cooperation, where one individual incurs a cost to help another, is a fundamental
      building block of the natural world and human society. It has been suggested that
      costly punishment can promote the evolution of cooperation, with the threat of
      punishment deterring free-riders. Recent experiments, however, have revealed the
      existence of 'antisocial' punishment, where non-cooperators punish cooperators.
      While various theoretical models find that punishment can promote the evolution
      of cooperation, these models a priori exclude the possibility of antisocial
      punishment. Here we extend the standard theory of optional public goods games to
      include the full set of punishment strategies. We find that punishment no longer
      increases cooperation, and that selection favours substantial levels of
      antisocial punishment for a wide range of parameters. Furthermore, we conduct
      behavioural experiments, showing results consistent with our model predictions.
      As opposed to an altruistic act that promotes cooperation, punishment is mostly a
      self-interested tool for protecting oneself against potential competitors.

PMID- 21847109
TI  - Heterothermy in growing king penguins.
AB  - A drop in body temperature allows significant energy savings in endotherms, but
      facultative heterothermy is usually restricted to small animals. Here we report
      that king penguin chicks (Aptenodytes patagonicus), which are able to fast for up
      to 5 months in winter, undergo marked seasonal heterothermy during this period of
      general food scarcity and slow-down of growth. They also experience short-term
      heterothermy below 20  degrees C in the lower abdomen during the intense
      (re)feeding period in spring, induced by cold meals and adverse weather. The
      heterothermic response involves reductions in peripheral temperature, reductions
      in thermal core volume and temporal abandonment of high core temperature. Among
      climate variables, air temperature and wind speed show the strongest effect on
      body temperature, but their effect size depends on physiological state. The
      observed heterothermy is remarkable for such a large bird (10 kg before fasting),
      which may account for its unrivalled fasting capacity among birds.

PMID- 21847110
TI  - Editing of human K(V)1.1 channel mRNAs disrupts binding of the N-terminus tip at
      the intracellular cavity.
AB  - In the nervous system, A->I RNA editing has an important role in regulating
      neuronal excitability. Ligand-gated membrane receptors, synaptic proteins, as
      well as ion channels, are targets for recoding by RNA editing. Although scores of
      editing sites have been identified in the mammalian brain, little is known about
      the functional alterations that they cause, and even less about the mechanistic
      underpinnings of how they change protein function. We have previously shown that
      an RNA editing event (I,400 V) alters the inner permeation pathway of human
      K(V)1.1, modifying the kinetics of fast inactivation. Here we show that the
      channel's inactivation gate enters deep into the ion permeation pathway and the
      very tip establishes a direct hydrophobic interaction with the edited position.
      By converting I to V, the intimacy of the interaction is reduced, allowing the
      inactivation gate to unbind with much faster kinetics.

PMID- 21847111
TI  - From computational discovery to experimental characterization of a high hole
      mobility organic crystal.
AB  - For organic semiconductors to find ubiquitous electronics applications, the
      development of new materials with high mobility and air stability is critical.
      Despite the versatility of carbon, exploratory chemical synthesis in the vast
      chemical space can be hindered by synthetic and characterization difficulties.
      Here we show that in silico screening of novel derivatives of the dinaphtho[2,3
      b:2',3'-f]thieno[3,2-b]thiophene semiconductor with high hole mobility and air
      stability can lead to the discovery of a new high-performance semiconductor. On
      the basis of estimates from the Marcus theory of charge transfer rates, we
      identified a novel compound expected to demonstrate a theoretic twofold
      improvement in mobility over the parent molecule. Synthetic and electrical
      characterization of the compound is reported with single-crystal field-effect
      transistors, showing a remarkable saturation and linear mobility of 12.3 and 16
      cm(2) V(-1) s(-1), respectively. This is one of the very few organic
      semiconductors with mobility greater than 10 cm(2) V(-1) s(-1) reported to date.

PMID- 21847112
TI  - Measuring single-nanoparticle wetting properties by freeze-fracture shadow
      casting cryo-scanning electron microscopy.
AB  - Nanoparticles at fluid interfaces are central to a rapidly increasing range of
      cutting-edge applications, including drug delivery, uptake through biological
      membranes, emulsion stabilization and the fabrication of nanocomposites.
      Understanding nanoscale wetting is a challenging issue, still unresolved for
      individual nanoparticles, and is essential in designing nanoparticle-building
      blocks with controlled surface properties. The core information about the
      structural and thermodynamic properties of particles at fluid interfaces is
      enclosed in the three-phase contact angle theta. Here we present a novel in situ
      method, on the basis of freeze-fracture shadow-casting cryo-scanning electron
      microscopy, that allows the measurement of contact angles of individual
      nanoparticles with 10 nm diameter, and thus greatly surpasses the current state
      of the art. We study hydrophilic and hydrophobic, organic and inorganic
      nanoparticles, demonstrating general applicability to systems of fundamental and
      applied nanotechnological interest. Significant heterogeneity in the wetting of
      nanoparticles is observed.

PMID- 21847113
TI  - Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human
      pathogen.
AB  - Synthetic biology aims to systematically design and construct novel biological
      systems that address energy, environment, and health issues. Herein, we describe
      the development of a synthetic genetic system, which comprises quorum sensing,
      killing, and lysing devices, that enables Escherichia coli to sense and kill a
      pathogenic Pseudomonas aeruginosa strain through the production and release of
      pyocin. The sensing, killing, and lysing devices were characterized to elucidate
      their detection, antimicrobial and pyocin release functionalities, which
      subsequently aided in the construction of the final system and the verification
      of its designed behavior. We demonstrated that our engineered E. coli sensed and
      killed planktonic P. aeruginosa, evidenced by 99% reduction in the viable cells.
      Moreover, we showed that our engineered E. coli inhibited the formation of P.
      aeruginosa biofilm by close to 90%, leading to much sparser and thinner biofilm
      matrices. These results suggest that E. coli carrying our synthetic genetic
      system may provide a novel synthetic biology-driven antimicrobial strategy that
      could potentially be applied to fighting P. aeruginosa and other infectious
      pathogens.

PMID- 21847116
TI  - MET phosphorylation predicts poor outcome in small cell lung carcinoma and its
      inhibition blocks HGF-induced effects in MET mutant cell lines.
AB  - BACKGROUND: Small cell lung carcinoma (SCLC) has poor prognosis and remains
      orphan from targeted therapy. MET is activated in several tumour types and may be
      a promising therapeutic target. METHODS: To evaluate the role of MET in SCLC, MET
      gene status and protein expression were evaluated in a panel of SCLC cell lines.
      The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in
      basal and hepatocyte growth factor (HGF)-stimulated conditions.
      Immunohistochemistry for MET and p-MET was performed in human SCLC samples and
      association with outcome was assessed. RESULTS: In MET mutant SCLC cells, HGF
      induced MET phosphorylation, increased proliferation, invasiveness and clonogenic
      growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced
      effects. In clinical samples, total MET and p-MET overexpression were detected in
      54% and 43% SCLC tumours (n = 77), respectively. MET phosphorylation was
      associated with poor median overall survival (132 days) vs p-MET negative cases
      (287 days) (P < 0.001). Phospho-MET retained its prognostic value in a
      multivariate analysis. CONCLUSIONS: MET activation resulted in a more aggressive
      phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this
      phenotype. In patients with SCLC, MET activation was associated with worse
      prognosis, suggesting a role in the adverse clinical behaviour in this disease.

PMID- 21847117
TI  - Relative prognostic value of TNM7 vs TNM6 in staging oesophageal cancer.
AB  - BACKGROUND: Stage migration consequent upon new cancer staging definitions may
      result in artifactual alterations in stage-specific survival and prognosis. The
      aim of this study was to determine the influence of the new TNM7 oesophageal
      cancer (OC) system on stage categorisation and survival when compared with
      historical controls. METHODS: A total of 202 patients diagnosed with operable OC
      and undergoing oesophagectomy (118 neoadjuvant chemotherapy) were studied.
      Patients originally classified and staged using TNM6 were retrospectively re
      staged using TNM7. RESULTS: Re-classification of TNM7 resulted in stage migration
      in 11.9% of patients (9.9% downstaged, 2.0% upstaged) when compared with TNM6.
      Five-year survival for stages I, II and III was 78%, 46% and 18% using TNM6,
      compared with 62%, 51% and 18%, respectively, using TNM7. Univariable analysis
      revealed that histological grade (P = 0.006), pT (P < 0.0001), TNM6 pN (P <
      0.0001), TNM7 pN (P < 0.0001), number of lymph node metastases (P < 0.0001), TNM6
      stage group (P < 0.0001), TNM7 stage group (P < 0.0001) and TNM7 prognostic group
      (P < 0.0001) were all associated with survival. Multivariable analysis revealed
      that only the TNM7 prognostic group was independently and significantly
      associated with survival. CONCLUSION: TNM7 is a better prognostic tool than TNM6
      and represents an important advance in staging OC.

PMID- 21847114
TI  - Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell
      growth.
AB  - Oncogenes such as K-ras mediate cellular and metabolic transformation during
      tumorigenesis. To analyze K-Ras-dependent metabolic alterations, we employed 13C
      metabolic flux analysis (MFA), non-targeted tracer fate detection (NTFD) of 15N
      labeled glutamine, and transcriptomic profiling in mouse fibroblast and human
      carcinoma cell lines. Stable isotope-labeled glucose and glutamine tracers and
      computational determination of intracellular fluxes indicated that cells
      expressing oncogenic K-Ras exhibited enhanced glycolytic activity, decreased
      oxidative flux through the tricarboxylic acid (TCA) cycle, and increased
      utilization of glutamine for anabolic synthesis. Surprisingly, a non-canonical
      labeling of TCA cycle-associated metabolites was detected in both transformed
      cell lines. Transcriptional profiling detected elevated expression of several
      genes associated with glycolysis, glutamine metabolism, and nucleotide
      biosynthesis upon transformation with oncogenic K-Ras. Chemical perturbation of
      enzymes along these pathways further supports the decoupling of glycolysis and
      TCA metabolism, with glutamine supplying increased carbon to drive the TCA cycle.
      These results provide evidence for a role of oncogenic K-Ras in the metabolic
      reprogramming of cancer cells.

PMID- 21847118
TI  - Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia
      patients: a population-based study.
AB  - BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) are known to have
      increased risks of second cancer. The incidence of second cancers after CLL has
      not been reported in detail for Australia, a country with particularly high
      levels of ultraviolet radiation (UVR). METHODS: The study cohort comprised of all
      people diagnosed with a primary CLL between 1983 and 2005 in Australia.
      Standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs)
      were calculated using Australian population rates. RESULTS: Overall, the risk of
      any second incident cancer was more than double that of the general population
      (SIR=2.17, 95% confidence interval (CI)=2.07, 2.27) and remained elevated for at
      least 9 years after CLL. Risks were increased for many cancers, particularly
      melanoma (SIR=7.74, 95% CI=6.85, 8.72). The risk of melanoma increased at younger
      ages, but was constant across >9 years of follow-up. Chronic lymphocytic
      leukaemia patients also had an increased risk of death because of melanoma
      (SMR=4.79, 95% CI=3.83, 5.90) and non-melanoma skin cancer (NMSC; SMR=17.0, 95%
      CI=14.4, 19.8), suggesting that these skin cancers may be more aggressive in CLL
      patients. CONCLUSION: We speculate that a shared risk factor, such as general
      immune suppression, modulated by UVR exposure may explain the increased risk of
      melanoma and NMSC in CLL patients.

PMID- 21847119
TI  - Body mass index in early and middle-late adulthood and risk of localised,
      advanced and fatal prostate cancer: a population-based prospective study.
AB  - BACKGROUND: The relationships between body mass index (BMI) during early and
      middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the
      disease (localised, advanced) and fatal PCa is unclear. METHODS: A population
      based cohort of 36,959 Swedish men aged 45-79 years was followed up from January
      1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced
      cases were diagnosed) and through December 2007 for PCa mortality (225 fatal
      cases). RESULTS: From a competing-risks analysis, incidence of localised PCa was
      observed to be inversely associated with BMI at baseline (middle-late adulthood;
      rate ratio (RR) for 35 kg m(-2) when compared with 22 kg m(-2) was 0.69 (95% CI
      0.52-0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated
      with a nonstatistically significant increased risk (RR for every five-unit
      increase: 1.12 (0.88-1.43)) and BMI at age 30 with a decreased risk (RR for every
      five-unit increase: 0.72 (0.51-1.01)). CONCLUSION: Our results indicate an
      inverse association between obesity during middle-late, but not early adulthood,
      and localised PCa. They also suggest a dual association between BMI and fatal PCa
      -a decreased risk among men who were obese during early adulthood and an
      increased risk among those who were obese during middle-late adulthood.

PMID- 21847121
TI  - Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as
      heterodimerisation partners of MET in lung cancer with MET amplification.
AB  - BACKGROUND: MET is a receptor tyrosine kinase (RTK) whose gene is amplified in
      various tumour types. We investigated the roles and mechanisms of RTK
      heterodimerisation in lung cancer with MET amplification. METHODS: With the use
      of an RTK array, we identified phosphorylated RTKs in lung cancer cells with MET
      amplification. We examined the roles and mechanisms of action of these RTKs with
      immunoprecipitation, annexin V binding, and cell migration assays. RESULTS: We
      identified epidermal growth factor receptor (EGFR), human EGFR (HER)2, HER3, and
      RET in addition to MET as highly phosphorylated RTKs in lung cancer cells with
      MET amplification. Immunoprecipitation revealed that EGFR, HER2, HER3, and RET
      each formed a heterodimer exclusively with MET and that these associations were
      markedly reduced in extent by treatment with a MET kinase inhibitor. RNA
      interference-mediated depletion of EGFR, HER2, or HER3 induced apoptosis in
      association with inhibition of AKT and ERK signalling pathways, whereas depletion
      of HER2 or RET inhibited both cell migration and STAT3 signalling. CONCLUSION:
      Our data suggest that heterodimers of MET with EGFR, HER2, HER3, or RET have
      differential roles in tumour development, and they provide new insight into the
      function of trans-phosphorylated RTKs as heterodimerisation partners of MET in
      lung cancer with MET amplification.

PMID- 21847120
TI  - Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell)
      tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours.
AB  - BACKGROUND: OCT3/4 (POU5F1) is an established diagnostic immunohistochemical
      marker for specific histological variants of human malignant germ cell tumours
      (GCTs), including the seminomatous types and the stem cell component of non
      seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of
      pluripotency and the self-renewal of normal embryonic stem- and germ cells.
      Detection of expression of this transcription factor is complicated by the
      existence of multiple pseudogenes and isoforms. Various claims have been made
      about OCT3/4 expression in non-GCTs, possibly related to using nonspecific
      detection methods. False-positive findings undermine the applicability of OCT3/4
      as a specific diagnostic tool in a clinical setting. In addition, false-positive
      findings could result in misinterpretation of pluripotency regulation in solid
      somatic cancers and their stem cells. Of the three identified isoforms--OCT4A,
      OCT4B and OCT4B1--only OCT4A proved to regulate pluripotency. Up until now, no
      convincing nuclear OCT4A protein expression has been shown in somatic cancers or
      tissues. METHODS: This study investigates expression of the various OCT3/4
      isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ
      cell) cancers, including representative cell lines and xenografts. RESULTS: Using
      specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in
      undifferentiated GCTs. The OCT4B variant shows no difference in expression
      between GCTs (either differentiated or undifferentiated) and somatic cancers. In
      spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no
      OCT3/4 protein is detected. Significant positive correlations between all
      isoforms of OCT3/4 were identified in both tumours with and without a known stem
      cell component, possibly indicating synergistic roles of these isoforms.
      CONCLUSION: This study confirms that OCT4A protein only appears in seminomatous
      GCTs, embryonal carcinoma and representative cell lines. Furthermore, it
      emphasises that in order to correctly assess the presence of functional OCT3/4,
      both isoform specific mRNA and protein detection are required.

PMID- 21847122
TI  - Late symptoms in long-term gynaecological cancer survivors after radiation
      therapy: a population-based cohort study.
AB  - BACKGROUND: We surveyed the occurrence of physical symptoms among long-term
      gynaecological cancer survivors after pelvic radiation therapy, and compared with
      population-based control women. METHODS: We identified a cohort of 789 eligible
      gynaecological cancer survivors treated with pelvic radiation therapy alone or
      combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478
      women was randomly sampled from the Swedish Population Registry. Data were
      collected through a study-specific validated postal questionnaire with 351
      questions concerning gastrointestinal and urinary tract function, lymph oedema,
      pelvic bones and sexuality. Clinical characteristics and treatment details were
      retrieved from medical records. RESULTS: Participation rate was 78% for
      gynaecological cancer survivors and 72% for control women. Median follow-up time
      after treatment was 74 months. Cancer survivors reported a higher occurrence of
      symptoms from all organs studied. The highest age-adjusted relative risk (RR) was
      found for emptying of all stools into clothing without forewarning (RR 12.7),
      defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder
      (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR
      4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR
      3.6). Survivors treated with radiation therapy alone showed in general higher
      rates of symptoms. CONCLUSION: Gynaecological cancer survivors previously treated
      with pelvic radiation report a higher occurrence of symptoms from the urinary and
      gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic
      pain compared with non-irradiated control women. Health-care providers need to
      actively ask patients about specific symptoms in order to provide proper
      diagnostic investigations and management.

PMID- 21847123
TI  - Targeting both Notch and ErbB-2 signalling pathways is required for prevention of
      ErbB-2-positive breast tumour recurrence.
AB  - BACKGROUND: We reported that Notch-1, a potent breast oncogene, is activated in
      response to trastuzumab and contributes to trastuzumab resistance in vitro. We
      sought to determine the preclinical benefit of combining a Notch inhibitor (gamma
      secretase inhibitor (GSI)) and trastuzumab in both trastuzumab-sensitive and
      trastuzumab-resistant, ErbB-2-positive, BT474 breast tumours in vivo. We also
      studied if the combination therapy of lapatinib plus GSI can induce tumour
      regression of ErbB-2-positive breast cancer. METHODS: We generated orthotopic
      breast tumour xenografts from trastuzumab- or lapatinib-sensitive and trastuzumab
      resistant BT474 cells. We investigated the antitumour activities of two distinct
      GSIs, LY 411 575 and MRK-003, in vivo. RESULTS: Our findings showed that
      combining trastuzumab plus a GSI completely prevented (MRK-003 GSI) or
      significantly reduced (LY 411 575 GSI) breast tumour recurrence post-trastuzumab
      treatment in sensitive tumours. Moreover, combining lapatinib plus MRK-003 GSI
      showed significant reduction of tumour growth. Furthermore, a GSI partially
      reversed trastuzumab resistance in resistant tumours. CONCLUSION: Our data
      suggest that a combined inhibition of Notch and ErbB-2 signalling pathways could
      decrease recurrence rates for ErbB-2-positive breast tumours and may be
      beneficial in the treatment of recurrent trastuzumab-resistant disease.

PMID- 21847124
TI  - Lung cancer mortality in a cohort of UK cotton workers: an extended follow-up.
AB  - BACKGROUND: A recent systematic review and meta-analysis suggested that
      occupational exposure to endotoxins protects against lung cancer. To explore this
      hypothesis further, the follow-up of mortality of a cohort of 3551 workers, who
      were employed in the British cotton industry during 1966-1971, was extended by 23
      years. METHODS: Subjects had originally been recruited to a survey of respiratory
      disease, which collected information about occupation and smoking habits.
      Cumulative exposures to endotoxins were estimated from data on endotoxin levels
      by work areas in cotton mills. Risks of lung cancer were estimated using survival
      modelling. RESULTS: During follow-up, 2018 deaths were recorded before the age of
      90 years, including 128 deaths from lung cancer. After adjustment for smoking,
      hazard ratios (95% confidence intervals) for cumulative endotoxin exposures of
      <=30,000, >30,000 and <=200,000, >200,000 and <=400,000, >400,000 and <=600,000
      and >600,000 endotoxin units (EU) m(-3) years were 1, 0.8 (0.5-1.6), 0.7 (0.4
      1.3), 0.6 (0.3-1.0) and 0.5 (0.3-0.9), respectively (P for trend=0.005).
      CONCLUSION: Our findings strengthen the evidence that occupational exposure to
      endotoxins protects against lung cancer, and suggest that the effect depends on
      cumulative dose and persists after exposure ceases.

PMID- 21847125
TI  - Immune activation by combination human lymphokine-activated killer and dendritic
      cell therapy.
AB  - BACKGROUND: Optimal cellular immunotherapy for cancer should ideally harness both
      the innate and adaptive arms of the immune response. Lymphokine-activated killer
      cells (LAKs) can trigger early innate killing of tumour targets, whereas long
      term adaptive-specific tumour control requires priming of CD8+ cytotoxic
      lymphocytes (CTLs) following acquisition of tumour-associated antigens (TAAs) by
      antigen-presenting cells such as dendritic cells (DCs). As DCs stimulate both
      innate and adaptive effectors, combination cell therapy using LAKs and DCs has
      the potential to maximise anti-tumour immune priming. METHODS: Reciprocal
      activation between human clinical grade LAKs and DCs on co-culture, and its
      immune consequences, was monitored by cell phenotype, cytokine release and
      priming of both innate and adaptive cytotoxicity against melanoma targets.
      RESULTS: Co-culture of DCs and LAKs led to phenotypic activation of natural
      killer (NK) cells within the LAK population, which was associated with increased
      production of inflammatory cytokines and enhanced innate cytotoxicity against
      tumour cell targets. The LAKs reciprocally matured DCs, and the combination of
      LAKs and DCs, on addition of melanoma cells, supported priming of specific anti
      tumour CTLs better than DCs alone. CONCLUSION: Clinical-grade LAKs/DCs represents
      a practical, effective combination cell immunotherapy for stimulation of both
      innate and adaptive anti-tumour immunity in cancer patients.

PMID- 21847126
TI  - Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?
AB  - Aspirin inhibits the enzyme cyclooxygenase (Cox), and there is a significant body
      of epidemiological evidence demonstrating that regular aspirin use is associated
      with a decreased incidence of developing cancer. Interest focussed on selective
      Cox-2 inhibitors both as cancer prevention agents and as therapeutic agents in
      patients with proven malignancy until concerns were raised about their toxicity
      profile. Aspirin has several additional mechanisms of action that may contribute
      to its anti-cancer effect. It also influences cellular processes such as
      apoptosis and angiogenesis that are crucial for the development and growth of
      malignancies. Evidence suggests that these effects can occur through Cox
      independent pathways questioning the rationale of focussing on Cox-2 inhibition
      alone as an anti-cancer strategy. Randomised studies with aspirin primarily
      designed to prevent cardiovascular disease have demonstrated a reduction in
      cancer deaths with long-term follow-up. Concerns about toxicity, particularly
      serious haemorrhage, have limited the use of aspirin as a cancer prevention
      agent, but recent epidemiological evidence demonstrating regular aspirin use
      after a diagnosis of cancer improves outcomes suggests that it may have a role in
      the adjuvant setting where the risk:benefit ratio will be different.

PMID- 21847127
TI  - Paclitaxel-ifosfamide-carboplatin combination chemotherapy regimen in advanced
      uterine and adnexal malignant mixed Mullerian tumours.
AB  - BACKGROUND: Malignant mixed Mullerian tumours (MMMTs) of the uterus and adnexa
      represent aggressive gynaecologic malignancies with a high rate of loco-regional
      and distant failure. For that reason, we evaluated the paclitaxel-ifosfamide
      carboplatin (TICb) combination in patients with advanced MMMTs. METHODS: Female
      patients with advanced MMMTs, WHO-PS 0-2, no prior chemotherapy for systemic
      disease, unimpaired haemopoietic and organ function were eligible. Chemotherapy
      was administered at the following doses; paclitaxel: 175 mg m(-2) on day 1,
      ifosfamide: 2.0 g m(-2) day(-1)--days 1 and 2, and carboplatin at a target area
      under the curve 5 on day 2, with prophylactic G-CSF from day 3. RESULTS: Forty
      patients of a median age 61 (45-72) years, performance status 0-2 with advanced
      MMMTs of the uterus (n=34), tubes (n=2) or ovary (n=4) have entered and all were
      evaluable for response and toxicity. Responses were as follows: 27 out of 40
      (67.5%) evaluable patients responded, with 11 complete responses and 16 partial
      responses, while 10 had stable disease, and 3 developed progressive disease. The
      median response duration was 9 months (range, 4-40 months), median progression
      free survival 13 months (range, 3-42 months), while median overall survival 18
      months (range, 4-48 months). Grade 3/4 neutropenia was recorded in 22 out of 40
      (55%)--with 13 developing grade 4 (<=7 days) and 7 out of 40 (17.5%) of patients
      at least one episode of febrile neutropenia. CONCLUSION: In this study, it
      appears that the TICb combination, yielded important activity with manageable
      toxicity in females with advanced MMMTs warranting further randomised comparison
      with current standard regimens.

PMID- 21847128
TI  - Clinical evaluation of autologous gamma delta T cell-based immunotherapy for
      metastatic solid tumours.
AB  - BACKGROUND: Adoptive transfer of ex vivo expanded autologous Vgamma9Vdelta2 T
      cells may be of therapeutic benefit for cancer because of their potent direct
      cytotoxicity towards tumour cells, synergistic cytotoxicity when combined with
      aminobisphosphonates and enhancement of antibody-dependent cell-mediated
      cytotoxicity. METHODS: To determine the feasibility and clinical safety of
      therapy with ex vivo expanded, activated Vgamma9Vdelta2 T cells in combination
      with zoledronate, we enrolled 18 subjects with advanced solid tumours into a
      phase I clinical study. Administered indium(111)-oxine-labelled Vgamma9Vdelta2 T
      cells were tracked in a cohort of patients. RESULTS: Administered Vgamma9Vdelta2
      T cells had an activated effector memory phenotype, expressed chemokine receptors
      predictive of homing to peripheral tissues and were cytotoxic in vitro against
      tumour targets. Adoptively transferred Vgamma9Vdelta2 T cells trafficked
      predominantly to the lungs, liver and spleen and, in some patients, to metastatic
      tumour sites outside these organs. No dose-limiting toxicity was observed, but
      most patients progressed on study therapy. However, three patients administered
      Vgamma9Vdelta2 T cells while continuing previously ineffective therapy had
      disease responses, suggesting an additive effect. CONCLUSION: Therapy with
      aminobisphosphonate-activated Vgamma9Vdelta2 T cells is feasible and well
      tolerated, but therapeutic benefits appear only likely when used in combination
      with other therapies.

PMID- 21847129
TI  - Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary
      sinus squamous cell carcinoma.
AB  - BACKGROUND: On the basis of the microRNA (miRNA) expression signature of
      maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-874 was
      significantly reduced in cancer cells. We focused on the functional significance
      of miR-874 in cancer cells and identification of miR-874-regulated novel cancer
      networks in MSSCC. METHODS: We used PCR-based methods to investigate the
      downregulated miRNAs in clinical specimens of MSSCC. Our signature analyses
      identified 23 miRNAs that were significantly reduced in cancer cells, such as miR
      874, miR-133a, miR-375, miR-204, and miR-1. We focused on miR-874 as the most
      downregulated novel miRNA in our analysis. RESULTS: We found potential tumour
      suppressive functions such as inhibition of cancer cell proliferation and
      invasion. A molecular target search of miR-874 revealed that PPP1CA was directly
      regulated by miR-874. Overexpression of PPP1CA was observed in MSSCC clinical
      specimens. Silencing of the PPP1CA gene significantly inhibited cancer cell
      proliferation and invasion. CONCLUSION: The downregulation of miR-874 was a
      frequent event in MSSCC, which suggests that miR-874 functions as a tumour
      suppressive miRNA, directly regulating PPP1CA that has a potential role of an
      oncogene. The identification of novel miR-874-regulated cancer pathways could
      provide new insights into potential molecular mechanisms of MSSCC oncogenesis.

PMID- 21847131
TI  - Antimycins A(19) and A(20), two new antimycins produced by marine actinomycete
      Streptomyces antibioticus H74-18.
AB  - Two new antimycin antibiotics; that is antimycins A(19) (1) and A(20) (2), were
      isolated from a cultured broth of marine actinomycete Streptomyces antibioticus
      H74-18 together with antimycins A(1a) (3a) and A(1b) (3b), A(2a) (4), A(3a) (5a)
      and A(3b) (5b). Their structures were determined by spectroscopic methods in
      combination with X-ray diffraction. Antimycin A(19) possessed a chiral acyl chain
      and an alkyl branch. The absolute configuration of chiral acyl chain in 1 was
      determined by X-ray diffraction analysis. Antimycin A(20) (2) has the shortest
      and simplest acetoxy acyl chain in the antimycins family. All the antimycins (1
      5) showed potential antifungal activities against Candida albicans with MIC of
      about 5-10 MUg ml(-1).

PMID- 21847130
TI  - Accelerated BEP: a phase I trial of dose-dense BEP for intermediate and poor
      prognosis metastatic germ cell tumour.
AB  - BACKGROUND: We used bleomycin, etoposide, cisplatin (BEP), the most effective
      regimen in the treatment of germ cell tumours (GCTs) and increased dose-density
      by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and
      tolerability. METHODS: Sixteen male patients with intermediate or poor prognosis
      metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day
      cycle for a planned relative dose-density of 1.5 compared with standard BEP.
      RESULTS: Eleven intermediate and five poor prognosis patients were treated. In
      all, 14 of 16 patients completed the study treatment. Toxicities were comparable
      to previous studies using standard BEP, except for mucositis and haematological
      toxicity that were more severe. The overall relative dose-density for all 16
      patients was mean 1.38 (range 0.72-1.5; median 1.46). Complete response was
      achieved after chemotherapy alone in two patients (13%) and following
      chemotherapy plus surgery in nine additional patients (56%). Four patients (25%)
      had a partial response and normalised their marker levels. At a median follow-up
      of 4.4 years (range 2.1-6.8) the estimated 5-year progression-free survival
      probability is 81% (95% CI 64-100%). CONCLUSION: Accelerated BEP is tolerable
      without major additional toxicity. A randomised controlled trial will be required
      to obtain comparative efficacy data.

PMID- 21847133
TI  - Natural product chemistry for drug discovery.

PMID- 21847132
TI  - New milbemycins from mutant Streptomyces bingchenggensis X-4.

PMID- 21847134
TI  - Detection of cerebral microbleeds with quantitative susceptibility mapping in the
      ArcAbeta mouse model of cerebral amyloidosis.
AB  - Cerebral microbleeds (CMBs) are findings in patients with neurological disorders
      such as cerebral amyloid angiopathy and Alzheimer's disease, and are indicative
      of an underlying vascular pathology. A diagnosis of CMBs requires an imaging
      method that is capable of detecting iron-containing lesions with high sensitivity
      and spatial accuracy in the presence of potentially confounding tissue
      abnormalities. In this study, we investigated the feasibility of quantitative
      magnetic susceptibility mapping (QSM), a novel technique based on gradient
      recalled echo (GRE) phase data, for the detection of CMBs in the arcAbeta mouse,
      a mouse model of cerebral amyloidosis. Quantitative susceptibility maps were
      generated from phase data acquired with a high-resolution T(2)(*)-weighted GRE
      sequence at 9.4 T. We examined the influence of different regularization
      parameters on susceptibility computation; a proper adjustment of the
      regularization parameter minimizes streaking artifacts and preserves fine
      structures. In the present study, it is shown that QSM provides increased
      detection sensitivity of CMBs and improved contrast when compared with GRE
      magnitude imaging. Furthermore, QSM corrects for the blooming effect observed in
      magnitude and phase images and depicts both the localization and spatial extent
      of CMBs with high accuracy. Therefore, QSM may become an important tool for
      diagnosing CMBs in neurological diseases.

PMID- 21847135
TI  - Increased cerebral protein ISGylation after focal ischemia is neuroprotective.
AB  - Addition of a small peptide called ISG15 is known as ISGylation, which is an
      ubiquitin (ub)-like posttranslational modification. We currently show that focal
      ischemia induced by transient middle cerebral artery occlusion (MCAO) in adult
      mice significantly induces cortical protein ISGylation between 6 and 24 hours
      reperfusion. With two-dimensional western blotting, 45 proteins were observed to
      be significantly increased in ISGylation (by 1.8- to 9.7-fold) after focal
      ischemia compared with sham control. Immunochemistry showed that ISGylated
      proteins are localized in neurons within the ipsilateral striatum and in
      astroglia within the peri-infarct cortex of ischemic mice. When subjected to
      transient MCAO, ISG15(-/-) mice showed increased mortality, exacerbated
      infarction, and worsened neurologic recovery than did wild-type controls. In
      addition, mice lacking UBE1L (ub-activating enzyme E1-like protein, the first
      enzyme of the ISGylation cycle) also showed bigger infarcts when subjected to
      transient MCAO. Regional cerebral blood flow or other physiologic parameters were
      not significantly different in both knockouts compared with wild-type controls.
      These studies indicate that increased protein ISGylation might be an endogenous
      neuroprotective adaptation to minimize poststroke brain damage.

PMID- 21847136
TI  - Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live
      mouse brain using fluorescence lifetime unmixing.
AB  - Superoxide is the single-electron reduction product of molecular oxygen generated
      by mitochondria and the innate immune enzyme complex, nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase (Nox), and its isoforms. Initially
      identified as critical to the host defense against infection, superoxide has
      recently emerged as an important signaling molecule and as a proposed mediator of
      central nervous system injury in stroke, neurodegenerative conditions, and aging
      itself. Complete understanding of superoxide in central nervous system disease
      has been hampered by lack of noninvasive imaging techniques to evaluate this
      highly reactive, short-lived molecule in vivo. Here we describe a novel optical
      imaging technique to monitor superoxide real time in intact animals using a
      fluorescent probe compound and fluorescence lifetime contrast-based unmixing.
      Specificity for superoxide was confirmed using validated mouse models with
      enhanced or attenuated brain superoxide production. Application of fluorescence
      lifetime unmixing removed autofluorescence, further enhanced sensitivity and
      specificity of the technique, permitted visualization of physiologically relevant
      levels of superoxide, and allowed superoxide in specific brain regions (e.g.,
      hippocampus) to be mapped. Lifetime contrast-based unmixing permitted disease
      model-specific and brain region-specific differences in superoxide levels to be
      observed, suggesting this approach may provide valuable information on the role
      of mitochondrial and Nox-derived superoxide in both normal function and
      pathologic conditions in the central nervous system.

PMID- 21847137
TI  - Adherence to the Mediterranean diet and quality of life in the SUN Project.
AB  - BACKGROUND/OBJECTIVES: Mediterranean diet has been related with reduced morbidity
      and better well-being. The aim of this study was to assess whether the adherence
      to the Mediterranean diet were associated with mental and physical health related
      to quality of life. SUBJECTS/METHODS: This analysis included 11 015 participants
      with 4 years of follow-up in the SUN Project (a multipurpose cohort study based
      on university graduates from Spain). A validated 136-item food frequency
      questionnaire was used to assess the adherence to the Mediterranean diet at
      baseline, according to a nine-point score, presented in four categories (low, low
      moderate, moderate-high and high). Health-related quality of life (HRQL) was
      measured after 4 years of follow-up with the Spanish version of the SF-36 Health
      Survey. Generalized Linear Models were fitted to assess adjusted mean scores, the
      regression coefficients (beta) and their 95% confidence intervals (95% CIs) for
      the SF-36 domains according to categories of adherence to Mediterranean diet.
      RESULTS: Multivariate-adjusted models revealed a significant direct association
      between adherence to Mediterranean diet and all the physical and most mental
      health domains (vitality, social functioning and role emotional). Vitality
      (beta=0.50, 95% CI=0.32-0.68) and general health (beta=0.45, 95% CI=0.26-0.62)
      showed the highest coefficients. Mean values for physical functioning, role
      physical, bodily pain, general health and vitality domains were significantly
      better with increasing adherence to the Mediterranean diet. Those having improved
      their initial high diet scores have better scores in physical functioning,
      general health and vitality. CONCLUSIONS: Adherence to the Mediterranean diet
      seems to be a factor importantly associated with a better HRQL.

PMID- 21847138
TI  - TFEBulous control of traffic by mTOR.

PMID- 21847139
TI  - QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep.
AB  - Dissecting the genetic architecture of fitness-related traits in wild populations
      is key to understanding evolution and the mechanisms maintaining adaptive genetic
      variation. We took advantage of a recently developed genetic linkage map and
      phenotypic information from wild pedigreed individuals from Ram Mountain,
      Alberta, Canada, to study the genetic architecture of ecologically important
      traits (horn volume, length, base circumference and body mass) in bighorn sheep.
      In addition to estimating sex-specific and cross-sex quantitative genetic
      parameters, we tested for the presence of quantitative trait loci (QTLs),
      colocalization of QTLs between bighorn sheep and domestic sheep, and sex * QTL
      interactions. All traits showed significant additive genetic variance and genetic
      correlations tended to be positive. Linkage analysis based on 241 microsatellite
      loci typed in 310 pedigreed animals resulted in no significant and five
      suggestive QTLs (four for horn dimension on chromosomes 1, 18 and 23, and one for
      body mass on chromosome 26) using genome-wide significance thresholds (Logarithm
      of odds (LOD) >3.31 and >1.88, respectively). We also confirmed the presence of a
      horn dimension QTL in bighorn sheep at the only position known to contain a
      similar QTL in domestic sheep (on chromosome 10 near the horns locus; nominal
      P<0.01) and highlighted a number of regions potentially containing weight-related
      QTLs in both species. As expected for sexually dimorphic traits involved in male
      male combat, loci with sex-specific effects were detected. This study lays the
      foundation for future work on adaptive genetic variation and the evolutionary
      dynamics of sexually dimorphic traits in bighorn sheep.

PMID- 21847140
TI  - Functional analysis of a promoter variant identified in the CFTR gene in cis of a
      frameshift mutation.
AB  - In monogenic diseases, the presence of several sequence variations in the same
      allele may complicate our understanding of genotype-phenotype relationships. We
      described new alterations identified in a cystic fibrosis (CF) patient harboring
      a 48C>G promoter sequence variation associated in cis of a 3532AC>GTA mutation
      and in trans with the F508del mutation. Functional analyses including in vitro
      experiments confirmed the deleterious effect of the 3532GTA frameshift mutation
      through the creation of a premature termination codon. The analyses also revealed
      that the 48G promoter variant has a negative effect on both transcription and
      mRNA level, thus demonstrating the importance of analyzing all mutations or
      sequence variations with potential impact on CF transmembrane conductance
      regulator processing, even when the two known disease-causing mutations have
      already been detected. Our results emphasize the need to perform, wherever
      possible, functional studies that may greatly assist the interpretation of the
      disease-causing potential of rare mutation-associated sequence variations.

PMID- 21847141
TI  - Surname and Y chromosome in Southern Europe: a case study with Colom/Colombo.
AB  - According to most historians, Christopher Columbus was born in Genoa, Italy.
      However, based on some key facts in the discoverer's biography, as well as in the
      linguistic analysis of his texts, some historians and linguists believe that
      Columbus could have been of Catalan origin. A Ligurian Columbus would have
      carried the Colombo surname, whereas he would have been called Colom if he were
      Catalan. In order to test whether it would be possible to discriminate between a
      Ligurian or a Catalan origin were Columbus' Y-chromosome haplotype to be
      retrieved, we genotyped 17 Y-chromosome STRs in 238 Spanish (from Catalonia,
      Valencia, and the Balearic Islands) and French Colom men, and 114 North Italian
      Colombo (from Liguria, Lombardy, and Piedmont). The Italian samples and, in
      particular, the Lombard Colombos were genetically as diverse as the general
      population, and we found little evidence of clusters of haplotypes that could
      indicate descent from a single founder. Colombo is actually the most frequent
      surname in Lombardy, where foundlings and orphans used to be given the surname
      Colombo. By contrast, Y-chromosome diversity was reduced in the Iberian Colom,
      where most of the men had Y chromosomes belonging to a few lineages. This implies
      that a positive identification would be more likely if Columbus were of Catalan
      descent. In this study, we have shown the diverse dynamics of two surnames linked
      by their etymology, in what is, to the best of our knowledge, the first genetic
      analysis of a surname in Southern Europe.

PMID- 21847142
TI  - A systematic eQTL study of cis-trans epistasis in 210 HapMap individuals.
AB  - We aimed at identifying transcripts whose expression is regulated by a SNP-SNP
      interaction. Out of 47,294 expression phenotypes we used 3107 transcripts that
      survived an extensive quality control and 86,613 linkage disequilibrium-pruned
      SNP markers that have been genotyped in 210 individuals. For each transcript we
      defined cis-SNPs, tested them for epistasis with all trans-SNPs, and corrected
      all observed cis-trans-regulated expression effects for multiple testing. We
      determined that the expression of about 15% of all included transcripts is
      regulated by a significant two-locus interaction, which is more than expected (P
      = 2.86 * 10(-144)). Our findings suggest further that cis-markers with so called
      'marginal effects' are more likely to be involved in two-locus gene regulation
      than expected (P = 8.27 * 10(-05)), although the majority of interacting cis
      markers showed no one-locus regulation. Furthermore, we found evidence that gene
      mediated trans-effects are not a major source of epistasis, as no enrichment of
      genes has been found in close vicinity of trans-SNPs. In addition, our data
      support the notion that neither chromosomal regions nor cellular processes are
      enriched in epistatic interactions. Finally, some of the cis-trans regulated
      genes have been found in genome-wide association studies, which might be
      interesting for follow-up studies of the corresponding disorders. In summary, our
      results provide novel insights into the complex genome-transcriptome regulation.

PMID- 21847143
TI  - Identification and functional analysis of novel THAP1 mutations.
AB  - Mutations in THAP1 have been associated with dystonia 6 (DYT6). THAP1 encodes a
      transcription factor that represses the expression of DYT1. To further evaluate
      the mutational spectrum of THAP1 and its associated phenotype, we sequenced THAP1
      in 567 patients with focal (n = 461), segmental (n = 68), or generalized dystonia
      (n = 38). We identified 10 novel variants, including six missense substitutions
      within the DNA-binding Thanatos-associated protein domain (Arg13His, Lys16Glu,
      His23Pro, Lys24Glu, Pro26Leu, Ile80Val), a 1bp-deletion downstream of the nuclear
      localization signal (Asp191Thrfs*9), and three alterations in the untranslated
      regions. The effect of the missense variants was assessed using prediction tools
      and luciferase reporter gene assays. This indicated the Ile80Val substitution as
      a benign variant. The subcellular localization of Asp191Thrfs*9 suggests a
      disturbed nuclear import for this mutation. Thus, we consider six of the 10 novel
      variants as pathogenic mutations accounting for a mutation frequency of 1.1%.
      Mutation carriers presented mainly with early onset dystonia (<12 years in five
      of six patients). Symptoms started in an arm or neck and spread to become
      generalized in three patients or segmental in two patients. Speech was affected
      in four mutation carriers. In conclusion, THAP1 mutations are rare in unselected
      dystonia patients and functional analysis is necessary to distinguish between
      benign variants and pathogenic mutations.

PMID- 21847144
TI  - Urinary DEHP metabolites and fasting time in NHANES.
AB  - Exposure assessment analyses conducted in Europe have concluded that the primary
      pathway of exposure to di(2-ethylhexyl) phthalate (DEHP) is through the diet. The
      purpose of this study is to evaluate whether urinary DEHP metabolite data from
      the 2007-2008 National Health and Nutritional Examination Survey (NHANES)
      demonstrate relationships with reported food-fasting time consistent with diet as
      the predominant exposure pathway. Previous controlled-dosing data demonstrate
      that DEHP metabolite concentrations in urine first rise and then decline over
      time, with first-order elimination becoming evident at about 6 h post exposure.
      Regression of the concentrations of four key DEHP metabolites vs reported fasting
      times between 6 and 18 h in adults resulted in apparent population-based urinary
      elimination half-lives, consistent with those previously determined in a
      controlled-dosing experiment, supporting the importance of the dietary pathway
      for DEHP. For fasting times less than about 6 h, sampling session (morning,
      afternoon, or evening) affected the measured metabolite concentrations. Evening
      samples showed the highest metabolite concentrations, supporting a hypothesis of
      recent daily dietary exposures from multiple meals, whereas morning and afternoon
      samples for fasting times less than 6 h were similar and somewhat lower than
      evening samples, consistent with less-substantial early day dietary exposure.
      Variations in children's bodyweight-normalized creatinine excretion and food
      intake rates contribute to a strong inverse relationship between urinary DEHP
      metabolite concentrations and age under age 18. Finally, a previously published
      pharmacokinetic model for DEHP demonstrates that time since previous urinary
      void, a parameter not measured in NHANES, is predicted to result in non-random
      effects on measured urinary concentrations.

PMID- 21847145
TI  - Efficient image projection by Fourier electroholography.
AB  - An improved efficient projection of color images is presented. It uses a phase
      spatial light modulator with three iteratively optimized Fourier holograms
      displayed simultaneously--each for one primary color. This spatial division
      instead of time division provides stable images. A pixelated structure of the
      modulator and fluctuations of liquid crystal molecules cause a zeroth-order peak,
      eliminated by additional wavelength-dependent phase factors shifting it before
      the image plane, where it is blocked with a matched filter. Speckles are
      suppressed by time integration of variable speckle patterns generated by
      additional randomizations of an initial phase and minor changes of the signal.

PMID- 21847146
TI  - Wavefront coding technique for controlling thermal defocus aberration in an
      infrared imaging system.
AB  - We use a wavefront coding approach to control thermal defocus aberration in an IR
      imaging system. The design method of athermalized system using a wavefront coding
      technique is discussed. An athermalized long wave IR optical system, which works
      at temperatures ranging from -40  degrees C to 60  degrees C, is designed by
      employing a cubic phase mask. Computer simulations and the first experimental
      demonstration are executed to verify the performance of this wavefront coded
      athermalized system and to clarify the issues related to its implementation.

PMID- 21847147
TI  - Passively mode-locked fiber laser based on a hollow-core photonic crystal fiber
      filled with few-layered graphene oxide solution.
AB  - We demonstrate a nanosecond-pulse erbium-doped fiber laser that is passively mode
      locked by a hollow-core photonic crystal fiber filled with few-layered graphene
      oxide solution. Owing to the good solution processing capability of few-layered
      graphene oxide, which can be filled into the core of a hollow-core photonic
      crystal fiber through a selective hole filling process, a graphene saturable
      absorber can be successfully fabricated. The output pulses obtained have a center
      wavelength, pulse width, and repetition rate of 1561.2 nm, 4.85 ns, and 7.68 MHz,
      respectively. This method provides a simple and efficient approach to integrate
      the graphene into the optical fiber system.

PMID- 21847148
TI  - Observation of second-order hyper-Raman generation in LiNbO3 whispering-gallery
      mode disk resonators.
AB  - In this Letter we report experimental demonstration of nonlinear frequency
      conversion at several optical frequencies in a whispering-gallery mode resonator
      (WGMR). Because of the enhancement of nonlinear interactions inside a WGMR,
      interaction of a 1064 nm pump field with a LiNbO(3) disk produced a weak but
      measurable non-phase-matched 532 nm second-harmonic field at room temperature
      (>100  degrees C below the phase-matching temperature) for pump powers of a few
      tens of milliwatts. For higher pump powers, we observed the generation of four
      additional fields at 545, 559, 573, and 587 nm. The relative spectral shift
      between two consecutive fields corresponds to a 455 cm(-1) vibrational mode in
      LiNbO(3) crystal. Our preliminary analysis indicates that these fields are the
      result of a multiphonon hyper-Raman scattering in which two photons of the pump
      field are converted into one photon of a higher-frequency field and one or
      several optical phonons.

PMID- 21847149
TI  - Er-doped photonic crystal fiber amplifier with 70 W of output power.
AB  - We report for the first time, to the best of our knowledge, on a large mode area
      Er-doped photonic crystal fiber laser system. The fiber core had a diameter of 40
      MUm and NA of <0.04 leading to a mode field diameter of about 31 MUm around 1550
      nm wavelength. More than 70 W of single-frequency output power at 1556 nm could
      be extracted using a master-oscillator power-amplifier scheme. Near diffraction
      limited output beam quality has been verified by measuring the TEM(00) content
      with a nonconfocal scanning ring cavity.

PMID- 21847150
TI  - Dual-wavelength, two-crystal, continuous-wave optical parametric oscillator.
AB  - We report a cw optical parametric oscillator (OPO) in a novel architecture
      comprising two nonlinear crystals in a single cavity, providing two independently
      tunable pairs of signal and idler wavelengths. Based on a singly resonant
      oscillator design, the device permits access to arbitrary signal and idler
      wavelength combinations within the parametric gain bandwidth and reflectivity of
      the OPO cavity mirrors. Using two identical 30 mm long MgO:sPPLT crystals in a
      compact four-mirror ring resonator pumped at 532 nm, we generate two pairs of
      signal and idler wavelengths with arbitrary tuning across 850-1430 nm, and
      demonstrate a frequency separation in the resonant signal waves down to 0.55 THz.
      Moreover, near wavelength-matched condition, coherent energy coupling between the
      resonant signal waves, results in reduced operation threshold and increased
      output power. A total output power >2.8 W with peak-to-peak power stability of
      16% over 2 h is obtained.

PMID- 21847151
TI  - Gas spectroscopy and optical path-length assessment in scattering media using a
      frequency-modulated continuous-wave diode laser.
AB  - Simultaneous assessment of the spectroscopic absorption signal of gas enclosed in
      a scattering medium and the corresponding optical path length of the probing
      light is demonstrated using a single setup. Sensitive gas absorption measurements
      are performed by a tunable diode laser using wavelength-modulation spectroscopy,
      while the path length is evaluated by the frequency-modulated cw technique
      commonly used in the field of telecommunication. Proof-of-principle measurements
      are demonstrated with water vapor as the absorbing gas and using polystyrene foam
      as an inhomogeneously scattering medium. The combination of these techniques
      opens up new possibilities for straightforward evaluation of gas presence and
      exchange in scattering media.

PMID- 21847152
TI  - Volume polarization holographic recording in thick phenanthrenequinone-doped
      poly(methyl methacrylate) photopolymer.
AB  - Volume polarization holographic recording in phenanthrenequinone-doped poly
      (methyl methacrylate) photopolymer is obtained. Photoinduced birefringence in a 2
      mm thick sample is measured by a phase-modulated ellipsometry. The birefringence
      induced in this material by linearly polarized beam at 514 nm reaches 1.2*10(-5).
      In addition, ability for recording volume polarization grating using two
      different polarization configurations is demonstrated and compared. The
      experimental results show that the diffraction efficiency of the hologram reaches
      to ~40% by using two orthogonal circularly polarized beams.

PMID- 21847153
TI  - Higher-order optical resonance node detection of integrated disk microresonator.
AB  - We have demonstrated higher-order optical resonance node detection by using an
      integrated disk microresonator from through port of the coupling bus waveguide.
      In addition to the fundamental mode, the disk resonator has higher-order
      whispering gallery modes. The excited second-order higher-order mode has a node
      at the position where the electromagnetic energy of the fundamental mode is close
      to a maximum. This high resolution measurement of optical resonance mode profile
      has a variety of applications for optical sensing and detection. The self
      referencing characteristics of the two optical resonance modes have potential to
      achieve optical detection independent of external perturbation, such as
      temperature change.

PMID- 21847154
TI  - Microfabricated surface ion trap on a high-finesse optical mirror.
AB  - A novel approach to optics integration in ion traps is demonstrated based on a
      surface electrode ion trap that is microfabricated on top of a dielectric mirror.
      Additional optical losses due to fabrication are found to be as low as 80 ppm for
      light at 422 nm. The integrated mirror is used to demonstrate light collection
      from, and imaging of, a single Sr88(+) ion trapped 169+/-4 MUm above the mirror.

PMID- 21847156
TI  - Full-field supercritical angle fluorescence microscopy for live cell imaging.
AB  - We introduce a full-field fluorescence imaging technique with axial confinement
      of about 100 nm at the sample/substrate interface. Contrary to standard surface
      imaging techniques, this confinement is obtained through emission filtering. This
      technique is based on supercritical emission selectivity. It can be implemented
      on any epifluorescence microscope with a commercial high numerical aperture
      objective and offers a real-time surface imaging capability. This technique is of
      particular interest for live cell membrane and adhesion studies. Using human
      embryonic kidney cells, we show that one can observe simultaneously the surface
      and in-depth cell phenomena.

PMID- 21847155
TI  - Spectrally resolving single-shot polarimeter.
AB  - We demonstrate a spectrally resolving single-shot polarimeter. The system
      consists of a commercial imaging spectrograph, modified by a birefringent wedge
      and a segmented polarizer. The physical operating principle and limitations of
      the apparatus as well as preliminary polarimetric measurements on the emission of
      random lasers are reported.

PMID- 21847157
TI  - Guided mode resonance in subwavelength metallodielectric free-standing grating
      for bandpass filtering.
AB  - We present the experimental study of a free-standing metallic guided-mode
      resonant structure, for bandpass filtering applications in the mid-IR wavelength
      range. Structure consists of a subwavelength gold grating with narrow slits
      deposited on a silicon nitride membrane. High optical transmission is measured
      with up to 78% transmission at resonance. Angularly resolved spectra are
      presented revealing Fano-type resonance.

PMID- 21847159
TI  - Relaxed fabrication tolerance for self-imaging photonic crystal waveguide
      splitters using a tapered multimode interference region.
AB  - The power imbalance between different waveguide outputs is compensated by
      manipulating the dispersion of the guided propagation in the multimode
      interference (MMI) region. This is attainable using a tapered region at the
      beginning of the MMI region that has been verified through simulation and
      experiment. From this, the fabrication tolerance for the diameters of holes in a
      tapered 1*3 photonic crystal waveguide (PhCW) splitter is relaxed up to a range
      of at least 27 nm. The output power is well-balanced to within 1 dB. The
      effective bandwidth of the splitters shifts only around 13 nm, for a reduction of
      10 nm in the diameter of the PhCW holes. The optimized component is an
      outstanding ultracompact 1*3 splitter for the photonic integrated circuit (PIC).

PMID- 21847160
TI  - High-power tandem pumped fiber amplifier with an output power of 2.9 kW.
AB  - We report on a high power fiber amplifier tandem pumped by an industrial style
      thin-disk laser. An output power of 1 kW and a very good slope efficiency of 73%
      have been obtained for a state-of-the-art photonic crystal fiber originally
      designed for short-pulse amplification. We also compare this result to an
      experiment, where a power of 2.9 kW could be obtained from a step-index large
      mode-area fiber with the same slope efficiency.

PMID- 21847161
TI  - Calibration of a wide angle stereoscopic system.
AB  - Inaccuracies in the calibration of a stereoscopic system appear with errors in
      point correspondences between both images and inexact points localization in each
      image. Errors increase if the stereoscopic system is composed of wide angle lens
      cameras. We propose a technique where detected points in both images are
      corrected before estimating the fundamental matrix and the lens distortion
      models. Since points are corrected first, errors in point correspondences and
      point localization are avoided. To correct point location in both images,
      geometrical and epipolar constraints are imposed in a nonlinear minimization
      problem. Geometrical constraints define the point localization in relation to its
      neighbors in the same image, and eipolar constraints represent the location of
      one point referred to its corresponding point in the other image.

PMID- 21847162
TI  - Multimode interference devices for focusing in microfluidic channels.
AB  - Low-cost, compact, automated optical microsystems for chemical analysis, such as
      microflow cytometers for identification of individual biological cells, require
      monolithically integrated microlenses for focusing in microfluidic channels, to
      enable high-resolution scattering and fluorescence measurements. The multimode
      interference device (MMI), which makes use of self-imaging in multimode
      waveguides, is shown to be a simple and effective alternative to the microlens
      for microflow cytometry. The MMIs have been designed, realized, and integrated
      with microfluidic channels in a silica-based glass waveguide material system.
      Focal spot sizes of 2.4 MUm for MMIs have been measured at foci as far as 43.7
      MUm into the microfluidic channel.

PMID- 21847163
TI  - Accuracy enhancement of digital image correlation with B-spline interpolation.
AB  - The interpolation algorithm plays an essential role in the digital image
      correlation (DIC) technique for shape, deformation, and motion measurements with
      subpixel accuracies. At the present, little effort has been made to improve the
      interpolation methods used in DIC. In this Letter, a family of recursive
      interpolation schemes based on B-spline representation and its inverse gradient
      weighting version is employed to enhance the accuracy of DIC analysis. Theories
      are introduced, and simulation results are presented to illustrate the
      effectiveness of the method as compared with the common bicubic interpolation.

PMID- 21847164
TI  - Optimal complex field holographic projection.
AB  - We describe a technique that uses complex field holograms to project three
      dimensional light patterns. Holographic projection commonly uses phase-only
      encoding since accurately representing complex holograms using both amplitude and
      phase spatial light modulators reduces the optical throughput significantly.
      Here, we use a lossless projection via the generalized phase contrast method to
      produce the necessary amplitude pattern required for complex field holographic
      projection. We numerically evaluate the technique and demonstrate high optical
      throughput with reduced undesired high diffraction orders.

PMID- 21847165
TI  - Scaling pseudo-Zernike expansion coefficients to different pupil sizes.
AB  - Orthogonal polynomials are routinely used to represent complex surfaces over a
      specified domain. In optics, Zernike polynomials have found wide application in
      optical testing, wavefront sensing, and aberration theory. This set is orthogonal
      over the continuous unit circle matching the typical shape of optical components
      and pupils. A variety of techniques has been developed to scale Zernike expansion
      coefficients to concentric circular subregions to mimic, for example, stopping
      down the aperture size of an optical system. Here, similar techniques are used to
      rescale the expansion coefficients to new pupil sizes for a related orthogonal
      set: the pseudo-Zernike polynomials.

PMID- 21847166
TI  - Driving and analysis of micro-objects by digital holographic microscope in
      microfluidics.
AB  - We propose an optical configuration in which floating particles in a microfluidic
      chamber can be characterized by an interference microscopy configuration to
      obtain quantitative phase-contrast maps. The configuration is simply made by two
      laser beams from the same laser source. One beam provides the optical forces for
      driving the particle along appropriate paths, but at same time works as the
      object illumination beam in the holographic microscope. The second beam plays the
      role of the reference beam, allowing recording of an interference fringe pattern
      (i.e., the digital hologram) in an out-of-focus image plane. The system and
      method are illustrated and experimental results are offered for polymeric
      particles as well as for in vitro cells with the aim to demonstrate the approach.

PMID- 21847167
TI  - Gap surface plasmon polaritons enhanced by a plasmonic lens.
AB  - We numerically investigate the optical field enhancement based on gap surface
      plasmon polaritons (GSPPs) that are enhanced by propagating surface waves
      launched by a circular slit at a metal-dielectric interface. The optical field
      enhancement originates not only from multiple scattering and coupling of GSPPs in
      the spacer region between two metal layers but also from propagating surface
      plasmon polaritons (SPPs) launched by a circular plasmonic lens. We find that the
      combination of the GSPPs and the propagating SPPs launched by the plasmonic lens
      can achieve extremely strong field confinement, and we find that the surface
      enhanced Raman scattering (SERS) enhancement factor can be up to 10(15) at the
      tip of the equilateral triangular nanostructures. The structure proposed here is
      expected to find promising applications where strong field enhancement is
      desired, such as optical sensing with the SERS effect.

PMID- 21847168
TI  - Why can soliton explosions be controlled by higher-order effects?
AB  - We investigate numerically the impact of some higher-order effects, namely, self
      frequency shift, self-steepening, and third-order dispersion, on the erupting
      soliton solutions of the quintic complex Ginzburg-Landau equation. We consider
      particularly the impact of these higher-order effects in the spectral domain from
      which we can describe the pulse characteristics in the time domain. These effects
      can filter in different ways the spectral perturbations that contribute to pulse
      explosions. We show that a proper combination of the three higher-order effects
      can provide a filtering of the spectral perturbations in such a way that a stable
      fixed-shape pulse propagation is achieved.

PMID- 21847170
TI  - Sm3+ photoreduction in BaCl2 nanophases precipitated fluoroaluminate glasses
      under femtosecond laser irradiation.
AB  - Photoreduction of samarium-doped BaCl(2)-modified aluminofluoride glass by
      femtosecond laser irradiation and x-ray irradiation were investigated.
      Photoluminescence of samarium ions indicated that photoreduction of Sm(3+)
      >Sm(2+) efficiently occurred in glass samples containing more than 5 mol.%
      BaCl(2) after femtosecond laser irradiation, while dramatic change was not
      observed by x-ray irradiation. Transmission electron microscope results revealed
      that BaCl(2) nanophases only precipitated from glass matrix with a high BaCl(2)
      content by focusing femtosecond laser irradiation. Samarium ions were selectively
      incorporated into the precipitated nanophases, resulting in the enhancement of
      Sm(3+) photoreduction under lower laser power.

PMID- 21847169
TI  - Algebraic bright and vortex solitons in defocusing media.
AB  - We demonstrate that spatially inhomogeneous defocusing nonlinear landscapes with
      the nonlinearity coefficient growing toward the periphery as (1+|r|(alpha))
      support one- and two-dimensional fundamental and higher-order bright solitons, as
      well as vortex solitons, with algebraically decaying tails. The energy flow of
      the solitons converges as long as nonlinearity growth rate exceeds the
      dimensionality, i.e., alpha>D. Fundamental solitons are always stable, while
      multipoles and vortices are stable if the nonlinearity growth rate is large
      enough.

PMID- 21847171
TI  - Optical fiber-coupled InGaAs-based terahertz time-domain spectroscopy system.
AB  - The successful demonstration of an optical fiber-coupled terahertz time-domain
      spectroscopy (THz-TDS) system is described in this study. The terahertz output
      power of the emitter with two optical band rejection filters was 132 nW, which is
      an improvement of 70% over the output power without any filters. This improvement
      is due to the suppression of an optical modulated signal that is reverse
      generated when an alternating current bias exceeding a certain threshold is
      applied to the emitter. Under the optimal alignment conditions, the terahertz
      detector in a fiber-coupled THz-TDS system clearly measured water vapor dips in
      the free space.

PMID- 21847172
TI  - High-speed three-dimensional shape measurements of objects with laser speckles
      and acousto-optical deflection.
AB  - Many three-dimensional (3D) shape measurement techniques in stereophotogrammetry
      with temporal coded structured illumination are limited to static scenes because
      the time for measurement is too long in comparison to the object speed. The
      measurement of moving objects result in erroneous reconstructions. This is
      apparent to reduce measurement time to overcome this limitation, which is often
      done by increasing the projection rate for illumination while shrinking the
      amount of images taken for reconstruction. The projection rate limits most
      applications in its speed because digital light processing (DLP) projectors,
      which are widely used, bring a limited projection rate along. Our approach, in
      contrast, does not take a DLP. Instead we use laser speckles as projected
      patterns which are switched using an acousto-optical deflector. The projection
      rate is 10* higher than what the fastest stripe projection systems to our
      knowledge achieve. Hence, we present this uncommon but potential approach for
      highspeed (~250 3Dfps= [3D measurements per second]), dense, and accurate 3D
      measurements of spatially separated objects and show the media that emphasizes
      the ability of accurate measurements while the objects under testing move.

PMID- 21847173
TI  - Tight focusing with a binary microaxicon.
AB  - Using a near-field scanning microscope (NT-MDT) with a 100 nm aperture cantilever
      held 1 MUm apart from a microaxicon of diameter 14 MUm and period 800 nm, we
      measure a focal spot resulting from the illumination by a linearly polarized
      laser light of wavelength lambda=532 nm, with its FWHM being equal to 0.58lambda,
      and the depth of focus being 5.6lambda. The rms deviation of the focal spot
      intensity from the calculated value is 6%. The focus intensity is five times
      larger than the maximal illumination beam intensity.

PMID- 21847174
TI  - Reverse optical forces in negative index dielectric waveguide arrays.
AB  - Nonconservative optical forces acting on dipolar particles are considered in
      longitudinally invariant optical fields. We demonstrate that the orientation of
      these forces is strictly dictated by the propagation vector associated with such
      field configurations. As a direct consequence of this, it is impossible to
      achieve a reversal of optical forces in homogeneous media. We show instead that
      translation invariant optical tractor fields can in fact be generated in the
      negative index environment produced in a special class of fully dielectric
      waveguide arrays.

PMID- 21847176
TI  - Frequency noise of free-running 4.6 MUm distributed feedback quantum cascade
      lasers near room temperature.
AB  - The frequency noise properties of commercial distributed feedback quantum cascade
      lasers emitting in the 4.6 MUm range and operated in cw mode near room
      temperature (277 K) are presented. The measured frequency noise power spectral
      density reveals a flicker noise dropping down to the very low level of <100
      Hz(2)/Hz at 10 MHz Fourier frequency and is globally a factor of 100 lower than
      data recently reported for a similar laser operated at cryogenic temperature.
      This makes our laser a good candidate for the realization of a mid-IR ultranarrow
      linewidth reference.

PMID- 21847175
TI  - Fraunhofer diffraction of light with orbital angular momentum by a slit.
AB  - We study the Fraunhofer diffraction problem while taking into account the orbital
      angular momentum of light. In this case, the phase singularity of the light beam
      is incident on the slit in two different cases: in one, it is incident slightly
      above the slit, and in the other it is centered on the slit. We observed that the
      symmetry and the fringe formation in the interference pattern strongly depend on
      the amount of orbital angular momentum and the slit position in relation to the
      beam.

PMID- 21847177
TI  - Wide measurement range scanning heterodyne interferometer utilizing astigmatic
      position sensing scheme.
AB  - A scanning heterodyne I/Q-interferometer scheme is proposed to overcome phase
      ambiguity caused by the periodic nature of its phase-dependent signal. A position
      sensing scheme using an astigmatic method in the confocal arrangement has been
      interfaced to the interferometer to retrieve the real phase value during a
      scanning process. The experimental results show that the vertical measurement
      range can be expanded up to 16 MUm. The potential of this interferometer on the
      scanning microscopy of a rough surface is discussed.

PMID- 21847178
TI  - Compact microfiber Bragg gratings with high-index contrast.
AB  - We fabricate fiber Bragg grating (FBG) in microfibers (MFs) using focused ion
      beam milling technique. By periodically etching 100 nm-depth grooves on the
      surface of silica MFs with diameters less than 2 MUm, evident grating features
      with transmission dip up to 15 dB are obtained. Because of the high-index
      contrast of the gratings structure, the length of the microfiber Bragg grating
      (MFBG) can be reduced to 500 MUm level. Using a 518 MUm-length 1.8 MUm-diameter
      MFBG, we also demonstrate sensitivity up to 660 nm per refractive index unit
      (RIU) for refractive index (RI) sensing. The highly compact MFBGs demonstrated
      here may serve as low-dimensional building blocks for miniaturized photonic
      components and devices.

PMID- 21847180
TI  - Active phasing a nine-element 1.14 kW all-fiber two-tone MOPA array using SPGD
      algorithm.
AB  - We demonstrated active phase locking a nine-element 1.1 kW all-fiber master
      oscillator power amplifier (MOPA) array using the stochastic parallel gradient
      descent (SPGD) blind optimization algorithm. Two spectrally combined single
      frequency seed lasers, which provide potential ability to suppress the stimulated
      Brillouin scattering effect, are employed as a master oscillator for the nine
      MOPA channels. The nine laser beams are tiled side by side into a 3*3 laser array
      with a fill factor of 40% in the near field. When the SPGD controller is enabled,
      the metric function is increased 4.1 times, and a visibility more than 90% of the
      interference pattern at the receiving plane is obtained. The computed phase
      residual error is less than lambda/15, despite the phase fluctuation of each
      channel.

PMID- 21847181
TI  - Fourier-transform, integrated-optic spatial heterodyne spectrometer on a silica
      based planar waveguide with 1 GHz resolution.
AB  - Spatial heterodyne spectrometers (SHS) can achieve high resolution with excellent
      optical throughput. We demonstrate a planar waveguide SHS incorporating 64
      asymmetric Mach-Zehnder interferometers and show measurements that verify 1 GHz
      resolution across a 64 GHz measurement range.

PMID- 21847179
TI  - High average power spectral beam combining of four fiber amplifiers to 8.2 kW.
AB  - We report on the incoherent beam combination of the four narrow-linewidth fiber
      amplifier chains running at different wavelengths. Each main amplifier stage
      consists of a large-mode-area photonic crystal fiber delivering more than 2 kW of
      optical power. The four output beams are spectrally combined to a single beam
      with an output power of 8.2 kW using a polarization-independent dielectric
      reflective diffraction grating mainly preserving the beam quality of the
      individual fiber amplifiers.

PMID- 21847182
TI  - Guiding light at the nanoscale: numerical optimization of ultrasubwavelength
      metallic wire plasmonic waveguides.
AB  - We present a comprehensive numerical analysis of the guiding of a photonic signal
      in the form of a strongly confined asymmetric surface plasmon polariton (SPP)
      mode along metallic nanowire waveguides. The proposed approach provides extremely
      high localization of the SPP mode, nanoscale integration density, and a feasible
      technological platform. The waveguide performance was studied over a broad range
      of subwavelength cross sections at a telecommunication wavelength. It was
      optimized using a conventional figure of merit for data transfer along a straight
      waveguide and an all-inclusive figure of merit has been introduced.

PMID- 21847183
TI  - Index of refraction engineering in five-level dressed interacting ground states
      atoms.
AB  - We present a five-level atomic system in which the index of refraction of a probe
      laser can be enhanced or reduced below unity with vanishing absorption in the
      region between pairs of absorption and gain lines formed by dressing of the atoms
      with a control laser and rf/microwave fields. By weak incoherent pumping of the
      population into a single metastable state, one can create several narrow
      amplifying resonances. At frequencies between these gain lines and additional
      absorption lines, there exist regions of vanishing absorption but resonantly
      enhanced index of refraction. In Rb vapors with density N in units of cm(-3), we
      predict an index of refraction up to n~?(1+1.2*10(-14)N) for the D1 line, which
      is more than an order of magnitude larger than other proposals for index of
      refraction enhancement. Furthermore, the index can be readily reduced below 1 by
      simply changing the sign of the probe or rf field detunings. This enhancement is
      robust with respect to homogeneous and inhomogeneous broadening.

PMID- 21847184
TI  - Design of passive polarization rotator based on silica photonic crystal fiber.
AB  - We propose and analyze a novel (to the best of our knowledge) design of a
      polarization rotator (PR) based on silica photonic crystal fiber. The proposed
      design has a rectangular core region with a slanted sidewall. The simulation
      results are obtained using the full vectorial finite difference method as well as
      the full vectorial finite difference beam propagation method. The numerical
      results reveal that the suggested PR can provide a nearly 100% polarization
      conversion ratio with a device length of 3102 MUm.

PMID- 21847185
TI  - Influence of anisotropic dipole matrix element on optical response of AB-stacked
      graphene superlattice.
AB  - When the polarization direction of the laser beam E lies on the graphene plane,
      the absorption spectrum A(omega)is isotropic and includes one sharp peak and some
      shoulders. As for E along the stacking direction, A(omega) is much weaker, and
      shows only one broadened peak. Because of the dipole matrix element M(cv), the
      optical excitations do not fully reflect the features of electronic structures
      [or the joint density of states (JDOS)]. M(cv) plays an important role in the
      relationship between A(omega) and JDOS. It is strongly dependent on E, showing an
      anisotropic property.

PMID- 21847187
TI  - 40 GHz mode-beating with 8 Hz linewidth and 64 fs timing jitter from a
      synchronized mode-locked quantum-dash laser diode.
AB  - Linewidth narrowing of the radio frequency beat-tones and the optical-modes is
      experimentally investigated in a ~40 GHz quantum-dash mode-locked laser diode
      subject to optical injection of 10 GHz pulses. In comparison to the 75 kHz
      linewidth exhibited by the beat-tones in passive mode-locking conditions, a
      remarkable reduction to less than 8 Hz is achieved when the laser is under
      optical injection. From this beat-tone signal, an integrated root-mean-square
      timing jitter of 64 fs is calculated. In addition, a quadratic profile of the
      optical linewidth with the wavelength is observed in active locking, reaching a
      minimum of 1.7 MHz for the longitudinal modes around 1530 nm and progressively
      increasing to 37.4 MHz for modes at 1525 nm.

PMID- 21847186
TI  - Generation of a twin beam at the cesium line and telecom wavelength by cavity
      phase matching.
AB  - Cavity phase matching has been recently demonstrated as a phase-matching method
      for efficient nonlinear frequency conversion in a microcavity. Here we extend it
      to the Type I configuration using a sub-coherent-length optical parametric
      oscillator consisting of an MgO-doped lithium niobate crystal sheet. It generates
      a tunable single-longitudinal-mode twin beam, which covers the cesium D2 line of
      852.1 nm and the extended band of optical communication. This microcavity is
      capable of peak output power of 58 kW with a maximum conversion efficiency of
      18.5%. Broad applications in the areas of light-atom interaction, spectroscopy,
      optical telecommunication, and quantum optics can be expected.

PMID- 21847188
TI  - Ultra-high-contrast few-cycle pulses for multipetawatt-class laser technology.
AB  - We report the generation of few-cycle multiterawatt light pulses with a temporal
      contrast of 10(10), when measured as close as 2 ps to the pulse's peak. Tens of
      picoseconds before the main pulse, the contrast value is expected to spread much
      beyond the measurement limit. Separate measurements of contrast improvement
      factors at different stages of the laser system indicate that real contrast
      values may reach 10(19) and 10(14), when measured 50 and 25 ps before the pulse's
      peak, respectively. The combination of the shortest pulse duration and the
      highest contrast renders our system a promising front-end architecture for future
      multipetawatt laser facilities.

PMID- 21847189
TI  - All-fiber micromachined microcell.
AB  - This Letter presents an open-path, all-fiber microcell and a micromachining
      method for its production. The proposed micromachining method utilizes the
      selective etching of a purposely designed phosphorus-doped fiber that is spliced
      in between two standard lead-in fibers. Microcells with various open optical-path
      lengths were successfully demonstrated. The proposed microcell can be used as a
      transmission cell or as a miniature Fabry-Perot resonator. The transmission
      losses and fringe contrast were experimentally investigated over a range of
      prototype microcells with different lengths. For example, the insertion losses
      below 1 dB were demonstrated for 50 MUm or shorter open path prototype
      microcells, when immersed in dematerialized water.

PMID- 21847190
TI  - Role of spatial coherence in Goos-Hanchen and Imbert-Fedorov shifts.
AB  - We present a theory for Goos-Hanchen (GH) and Imbert-Fedorov (IF) shifts for
      beams of light with arbitrary spatial coherence. By applying the well-known
      theory of partial spatial coherence, we can calculate explicitly spatial and
      angular GH and IF shifts for completely polarized beams of any shape and spatial
      coherence. For the specific case of a Gauss-Schell source, we find that only the
      angular part of GH and IF shifts is affected by the spatial coherence of the
      beam. A physical explanation of our results is given.

PMID- 21847191
TI  - Defect-induced whispering-gallery-mode resonances in optical microdisk
      resonators.
AB  - In this Letter we present results of theoretical and experimental studies of
      whispering-gallery modes in optical microdisk resonators interacting with
      subwavelength dielectric particles. We predict theoretically and confirm by
      direct observations that, contrary to the generally accepted models, both peaks
      of the particle-induced doublet of resonances are redshifted with respect to the
      position of the initial resonance.

PMID- 21847192
TI  - Technique for interaction of optical fields with turbulent medium containing
      particles.
AB  - We develop a method for transmission of stochastic fields through turbulent media
      (atmosphere, ocean, biotissues) containing randomly distributed particles. The
      method is based on the angular spectrum representation of stochastic,
      statistically stationary, scalar fields, the Rytov perturbation series for
      propagation in weakly fluctuating media, and the first Born approximation for
      weak scattering from particulate media. The results for transmission of the
      deterministic (laser) field may be obtained from our general results as a
      limiting case.

PMID- 21847193
TI  - Perfect extinction in subwavelength dual metallic transmitting gratings.
AB  - We investigate the strong electromagnetic coupling that settles in dual metallic
      grating structures. This coupling is evidenced to lead to a perfect optical
      extinction in the transmission spectrum. The behavior of this perfect extinction
      that strongly depends on the longitudinal space and the lateral displacement
      between the two gratings can be explained by a simple model that describes the
      interference between a propagating mode and a couple of evanescent modes. The
      results show that the electromagnetic transmission of the structure can be tuned
      by controlling the position of this perfect transmission extinction and thus pave
      the way to new types of infrared tunable filters.

PMID- 21847194
TI  - Ultraviolet band edge photorefractivity in LiNbO3:Sn crystals.
AB  - The ultraviolet (UV) band edge photorefractivity of Sn-doped LiNbO(3) (LN:Sn) at
      325 nm has been investigated. A sharp decrease of beam distortion, which is
      accompanied by a significant increase in the photoconductivity, is observed in
      LN:Sn crystals with Sn-doping concentrations at or above 2.0 mol%. The
      diffraction efficiency, the holographic recording sensitivity and response rate,
      and the two-wave coupling gain coefficient are greatly enhanced when the Sn
      doping concentration reaches 2.0 mol% or more. Unlike LiNbO(3) doped with Hf in
      which the UV gratings can be erased easily by a red beam, the UV gratings in
      LN:Sn can withstand long-term red beam illumination. Electrons are determined to
      be the dominant light-induced charge carriers responsible for the UV band edge
      photorefraction. The observed enhancement on the UV band edge photorefractivity
      is found to be associated with the showup of an absorption band around 325 nm in
      LN:Sn crystals with Sn-doping concentrations at or above 2.0 mol%.

PMID- 21847195
TI  - Directionality of terahertz emission from photoinduced gas plasmas.
AB  - Forward and backward terahertz emission by ionizing two-color laser pulses in gas
      is investigated by means of a simple semianalytical model based on Jefimenko's
      equations and rigorous Maxwell simulations in one and two dimensions. We find the
      emission in the backward direction has a much smaller spectral bandwidth than in
      the forward direction and explain this by interference effects. Forward terahertz
      radiation is generated predominantly at the ionization front and is thus almost
      not affected by the opacity of the plasma, in excellent agreement with results
      obtained from a unidirectional pulse propagation model.

PMID- 21847197
TI  - Measurement of the refractive index of highly turbid media: reply to comment.
AB  - Peiponen et al. [Opt. Lett.35, 4108 (2010)] have expressed concern that a
      theoretical model we proposed in Calhoun et al. [Opt. Lett.35, 1224 (2010)] for
      total internal reflection from a turbid medium may be inconsistent with the
      experimental data, in the sense that the model fails to take into account
      unexplained oscillations in our data. We show that their concern arises from
      misinterpretation of our data and theory, and is, therefore, unfounded. NOTE:
      Optics Letters apologizes to the authors for the delay in the publication of this
      Reply.

PMID- 21847196
TI  - Supercontinuum light source enables in vivo optical microangiography of capillary
      vessels within tissue beds.
AB  - This Letter reports on the use of a supercontinuum light source to achieve
      ultrahigh resolution and ultrahigh sensitive optical microangiography (OMAG)
      imaging of microcirculations within tissue beds in vivo. After passing through a
      specially designed optical filter with a passband of 120 nm centered on 800 nm,
      the light source is coupled into an optic-fiber-based OMAG system that provides a
      measured axial resolution of ~3 MUm over a ranging distance of 2 mm. Within this
      ranging distance, the system gives an averaged signal-to-noise ratio of 87 dB and
      a sensitivity roll-off of 7 dB at an A-scan rate of 70 kHz. We demonstrate the
      capability of the system to visualize a detailed microvascular perfusion map,
      including the single red blood cells within the capillaries, by imaging a mouse
      ear flap in vivo.

PMID- 21847198
TI  - Enhancing the sensitivity of fiber Mach-Zehnder interferometers using slow and
      fast light.
AB  - We demonstrate theoretically and experimentally that the sensitivity of a fiber
      Mach-Zehnder (M-Z) interferometer can be enhanced by coupling fiber ring
      resonators with it. The experimental results agree well with theoretical
      predications that combining slow light with fast light will further increase the
      sensitivity of a fiber M-Z interferometer.

PMID- 21847199
TI  - Tunable two-mirror interference lithography system for wafer-scale
      nanopatterning.
AB  - We have designed and analyzed a novel (to the best of our knowledge) two-beam
      interference lithography system for large-area (wafer-level) nanopatterning with
      enhanced tunability of pattern periodicities. The tunable feature has been
      achieved by placing two rotational mirrors in the expanded beam paths at
      regulated angles for a desired period. Theoretical analyses show that the
      effective pattern coverage area greater than a 4 in. (10 cm) wafer scale is
      attainable with a 325 nm (30 cm coherence length) HeCd laser and 4 in. (10 cm)
      mirrors, while the pattern coverage area is restrained by the overruling effects
      between the optical coherence and mirror size. The experimental results also
      demonstrate uniform nanopatterns at varying periods (250-750 nm) on 4 in. (10 cm)
      substrates, validating the theoretical analyses. The tunable two-mirror
      interferometer will offer a convenient and robust way to prepare large-area
      nanostructures on a wafer scale with superior tunability in their pattern
      periodicities.

PMID- 21847200
TI  - Generation of vector beam with space-variant distribution of both polarization
      and phase.
AB  - We present an idea to generate an arbitrary space-variant vector beam with
      structured polarization and phase distributions. The vector beams are synthesized
      from the left- and right-hand polarized light, each carrying different phase
      distributions. Both the phase and the state of polarization of vector beams can
      be tailored independently and dynamically by a spatial light modulator.

PMID- 21847201
TI  - Individual particle handling in a microfluidic system based on parallel laser
      trapping.
AB  - We present an optical trapping system combining individually addressable multiple
      laser traps with fluorescence spectroscopy. An in-line set of 64 near-IR laser
      diodes is used to create a line of individually addressable traps inside a
      microfluidic chip. This system is completed by an excitation/detection line for
      spectrally resolved fluorescence imaging of trapped particles. Highly parallel
      trapping in a constant flow (up to a few millimeters per second), fast particle
      handling rates (up to a few particles per second), and the possibility of
      recording fluorescence spectra of trapped objects lead to a performing
      bioanalytical platform, e.g., for highly parallel analysis and sorting.

PMID- 21847202
TI  - Single-molecule detection using continuous wave excitation of two-photon
      fluorescence.
AB  - Two-photon fluorescence (TPF) is one of the most important discoveries for
      biological imaging. Although a cw laser is known to excite TPF, its application
      in TPF imaging has been very limited due to the perceived low efficiency of
      excitation. Here we directly excited fluorophores with an IR cw laser used for
      optical trapping and achieved single-molecule fluorescence sensitivity: discrete
      stepwise photobleaching of enhanced green fluorescent proteins was observed. The
      single-molecule fluorescence intensity analysis and on-time distribution strongly
      indicate that a cw laser can generate TPF detectable at the single-molecule
      level, and thus opens the door to single-molecule TPF imaging using cw lasers.

PMID- 21847203
TI  - Pump-probe spectroscopy on photoinitiators for stimulated-emission-depletion
      optical lithography.
AB  - We report on femtosecond pump-probe experiments on two different photoinitiators
      in solution. These two molecules have recently appeared as attractive candidates
      for far-field optical lithography based on stimulated-emission-depletion (STED)
      inspired approaches aiming at beating Abbe's diffraction limit. For the case of 7
      diethylamino-3-thenoylcoumarin (DETC), we find that stimulated emission clearly
      dominates over excited-state absorption, whereas the opposite holds true for the
      case of isopropylthioxanthone. We argue that it is desirable that stimulated
      emission dominates over excited-state absorption as depletion mechanism in STED
      photoresists. Thus, DETC is an attractive corresponding photoinitiator.

PMID- 21847204
TI  - Plasmonic Airy beams with dynamically controlled trajectories.
AB  - We report the experimental generation and dynamic trajectory control of plasmonic
      Airy beams (PABs). The PABs are created by directly coupling free-space Airy
      beams to surface plasmon polaritons through a grating coupler on a metal surface.
      We show that the ballistic motion of the PABs can be reconfigured in real time by
      either a computer addressed spatial light modulator or mechanical means.

PMID- 21847205
TI  - High-contrast 1.16 PW Ti:sapphire laser system combined with a doubled chirped
      pulse amplification scheme and a femtosecond optical-parametric amplifier.
AB  - Based on a combined scheme of doubled chirped-pulse amplification and a
      femtosecond noncollinear optical-parametric amplifier, a high-contrast
      femtosecond laser pulse with energy of up to 32.3 J has been generated by
      improving the gain efficiency and boosting the pump energy to 120 J in the final
      amplifier. Our measurements show that the contrast ratio of the main laser pulse
      is around 10(10) within the time scale of -400 ps and the duration of compressed
      pulse is 27.9 fs, corresponding to a peak power of 1.16 PW.

PMID- 21847207
TI  - Spin Hall effect of light in metallic reflection.
AB  - We report the first measurement of the spin Hall effect of light (SHEL) on an air
      metal interface. The SHEL is a polarization-dependent out-of-plane shift on the
      reflected beam. For the case of metallic reflection with a linearly polarized
      incident light, both the spatial and angular variants of the shift are observed
      and are maximum for -45 degrees /45 degrees  polarization, but zero for pure s
      and p polarization. For an incoming beam with circular polarization states
      however, only the spatial out-of-plane shift is present.

PMID- 21847206
TI  - Influence of injection current on the synchronization and communication
      performance of closed-loop chaotic semiconductor lasers.
AB  - We numerically analyze the effect of an injection current on the synchronization
      and communication features of two chaotic external cavity semiconductor lasers in
      a closed-loop configuration. The simulation results demonstrate that, by
      moderately increasing the injection current, the efficient bandwidth of the
      chaotic carrier would be broadened, high quality chaos synchronization can be
      preserved, and the communication performance can be enhanced.

PMID- 21847208
TI  - Forming the graded-refractive-index antireflection layers on light-emitting
      diodes to enhance the light extraction.
AB  - Distributed antireflection (AR) layers with different composition ratios of ITO
      and SiO(2) formed on an ITO electrode of GaN-based LEDs provide substantial
      enhancement in light-extraction efficiency. By using the coradio frequency
      magnetron sputtering deposition, four 50 nm thick AR layers with graduated
      refractive indices were fabricated. The effect of the AR layers on enhancing the
      efficiency of the LED device was analyzed by electroluminescence (EL) and I-V
      measurements. As a result, the EL intensity of the LED device grown on the
      patterned sapphire substrate with AR layers was increased by up to 13% compared
      to the conventional patterned sapphire substrate-applied LED device without AR
      layers at a drive current of 20 mA. The AR layers on top of the LED device
      gradually changed the refractive indices between ITO (n=2.1) and air (n=1.0),
      which minimized the total internal reflection of generated light. And no
      degradation in the electrical characteristic of the LEDs was observed according
      to the I-V measurements.

PMID- 21847209
TI  - InP-based deep-ridge NPN transistor laser.
AB  - We report an InP-based deep-ridge NPN transistor laser (TL, lambda~1.5 MUm). By
      placing the quantum well (QW) active material above the heavily Zn-doped base
      layer, both the optical absorption of the heavily p-doped base material and the
      damage of the quality of the QWs resulted from the Zn diffusion into the QWs are
      decreased greatly. CW operation of the TL is achieved at -40  degrees C, which is
      much better than the shallow-ridge InP-based NPN TL. With future optimization of
      the growth procedure, significant improvement of the performance of the deep
      ridge InP-based NPN TLs is expected.

PMID- 21847210
TI  - Passive mode locking of an in-band-pumped Ho:YLiF4 laser at 2.06 MUm.
AB  - We demonstrate the passive mode-locking operation of an in-band-pumped Ho:YLiF(4)
      laser at 2.06 MUm using a semiconductor saturable absorber mirror based on
      InGaAsSb quantum wells. A transform-limited pulse train with minimum duration of
      1.1 ps and average power of 0.58 W has been obtained at a repetition frequency of
      122 MHz. A maximum output power of 1.7 W has been generated with a corresponding
      pulse duration of 1.9 ps.

PMID- 21847211
TI  - Depixelation of coherent fiber bundle endoscopy based on learning patterns of
      image prior.
AB  - We present an iterative method of eliminating pixelation artifacts from an
      endoscopic image acquired from a coherent fiber bundle imager. Our proposed
      approach for decoupling the honeycomb effect from the obtained sample image was
      formulated by using the prior probability for an approximate Bayesian framework
      in which the ideal complete image can be estimated by maximizing the posterior
      probability from the observed image. The maximization of the posterior
      probability from the original mask image (the mirrored fiber bundle imager
      structure) and the observed image (the sample image of the United States Air
      Force chart) has been performed by learning the image priors in the space of
      Markov random fields. By iteratively estimating the probability distribution, we
      reduced the noise effects from the mask image and recovered the ideal shape of
      the image. This method was efficient for automatically learning the sliding patch
      from the combination of projected kernels. The mask and observed images were
      obtained from en face images of the Fourier domain optical coherence tomography
      based on a common path interferometry scheme.

PMID- 21847212
TI  - Optical monitoring of PMD accumulation on a Pol-MUX phase-modulated signal using
      degree-of-polarization measurements.
AB  - We experimentally demonstrate a chromatic dispersion insensitive monitoring
      technique for monitoring of polarization mode dispersion and time misalignment in
      a 80 Gbit/s polarization-multiplexed return-to-zero differential phase-shift
      keying (Pol-MUX RZ-DPSK) signal using a polarimeter and degree-of polarization
      (DOP) measurements. This technique is modulation format independent (i.e.,
      applicable to both the phase- and amplitude-modulated data) and capable of
      measuring the fast change of polarization effects caused by vibration or other
      fast disturbances in the fiber link. We show that the monitored DOP of this
      signal decreases by 10.8% with differential group delay of 0-12 ps and decreases
      by 20% with a maximum misalignment of 12.5 ps between two orthogonally polarized
      RZ-DPSK channels. These measurements are less sensitive to chromatic dispersion
      of 0-400 ps/nm.

PMID- 21847214
TI  - Optical refractometer based on an asymmetrical twin-core fiber Michelson
      interferometer.
AB  - We report and demonstrate an optical refractometer based on a compact fiber
      Michelson interferometer. The Michelson interferometer is composed of an
      asymmetrical twin-core fiber containing a central core and a side core. By
      chemically etching a segment of the twin-core fiber until the side core is
      exposed, the effective index of the side core in the etched region is sensitive
      to the environmental refractive index, which leads to a shift of the transmission
      spectrum of the Michelson interferometer. The experimental results show that such
      a device has a refractive index resolution of more than 800 nm/refractive index
      unit in the range of 1.34-1.37.

PMID- 21847215
TI  - Spatial-spectral distribution of Rabi radiation generated in plasma.
AB  - We report observation and control of the spatial-spectral distributions of
      coherent, dynamic Rabi sideband radiation. The Rabi sidebands result from the
      interaction of a shaped picosecond probe laser of intensity 10(10) W cm(-2), with
      neutral excited atomic oxygen generated in a laser-induced microplasma. The
      spatial-spectral distribution is measured and compared for picosecond laser
      pulses having either an asymmetric temporal shape or a Gaussian temporal shape.
      The resulting spatial-spectral distributions are in quantitative agreement with
      theoretical predictions that account for the radial intensity distribution of the
      picosecond probe pulse.

PMID- 21847216
TI  - Anomalous retroreflection from strongly absorbing nanoporous semiconductors.
AB  - Pronounced retroreflection behavior is reported for a fishnet nanoporous strongly
      absorbing semiconductor material. Retroreflection features a half-cone about 0.35
      rad along with diffusive specular reflection for all angles of incidence.
      Retroreflection is apparent by the naked eye with daylight illumination and
      exhibits no selectivity with respect to wavelength and polarization of incident
      light featuring minor depolarization of retroreflected light. The reflectance in
      the backward direction measures 12% with respect to a white scattering etalon.
      The phenomenon can be classified neither as coherent backscattering nor as
      Anderson localization of light. The primary model includes light scattering from
      strongly absorptive and refractive superwavelength clusters existing within the
      porous fishnet structure. A reasonable qualitative explanation is based on the
      fact that strict retroreflection obeys shorter paths inside absorbing medium,
      whereas all alternative paths will lead to stronger absorption of light.

PMID- 21847213
TI  - Intense 2.7 MUm and broadband 2.0 MUm emission from diode-pumped Er3+/Tm3+/Ho(3+)
      doped fluorophosphate glass.
AB  - This Letter reports intense emission at 2.7 MUm and broadband emission at 2.0 MUm
      from Er(3+)/Tm(3+)/Ho(3+)-doped fluorophosphate glass. The fluorescence
      characteristics and energy transfer upon excitation of a conventional 980 nm
      laser diode are investigated. Based on the fluorescence spectra and lifetime
      measurement, the effect of Tm(3+) and Ho(3+) ions on intense 2.7 MUm emission in
      fluorophosphate glass is demonstrated. It is also found that the effective
      bandwidth of 2.0 MUm emission due to Tm(3+) and Ho(3+) ions can reach as high as
      196 nm. These results indicate that the advantageous spectroscopic
      characteristics of Er(3+)/Tm(3+)/Ho(3+) triply doped fluorophosphate glass
      together with the outstanding thermal properties may become an attractive host
      for the mid-IR solid state lasers.

PMID- 21847217
TI  - Acceleration control of Airy beams with optically induced refractive-index
      gradient.
AB  - We demonstrate both experimentally and theoretically controlled acceleration of
      one- and two-dimensional Airy beams in optically induced refractive-index
      potentials. Enhancement as well as reduction of beam acceleration are realized by
      changing the index gradient, while the beam shape is maintained during
      propagation through the linear optical potential. Our results of active
      acceleration manipulation in graded media are pertinent to Airy-type beam
      propagation in various environments.

PMID- 21847218
TI  - Induced transparency in nanoscale plasmonic resonator systems.
AB  - An optical effect analogous to electromagnetically induced transparency (EIT) is
      observed in nanoscale plasmonic resonator systems. The system consists of a slot
      cavity as well as plasmonic bus and resonant waveguides, where the phase-matching
      condition of the resonant waveguide is tunable for the generation of an obvious
      EIT-like coupled resonator-induced transparency effect. A dynamic theory is
      utilized to exactly analyze the influence of physical parameters on transmission
      characteristics. The transparency effect induced by coupled resonance may have
      potential applications for nanoscale optical switching, nanolaser, and slow-light
      devices in highly integrated optical circuits.

PMID- 21847219
TI  - Compact, 1.5 mJ, 450 MHz, CdSiP2 picosecond optical parametric oscillator near
      6.3 MUm.
AB  - We report a compact, efficient, high-energy, and high-repetition-rate mid-IR
      picosecond optical parametric oscillator (OPO) based on the new nonlinear
      material CdSiP(2) (CSP). The OPO is synchronously pumped by a master oscillator
      power amplifier system at 1064.1 nm, providing 1 MUs long macropulses
      constituting 8.6 ps micropulses at 450 MHz, and it can be tuned over 486 nm
      across 6091-6577 nm, covering the technologically important wavelength range for
      surgical applications. Using a compact (~30 cm) cavity and improved, high-quality
      nonlinear crystal, idler macropulse energy as high as 1.5 mJ has been obtained at
      6275 nm at a photon conversion efficiency of 29.5%, with >1.2 mJ over more than
      68% of the tuning range, for an input macropulse energy of 30 mJ. Both the signal
      and idler beams are recorded to have good beam quality with a Gaussian spatial
      profile, and the extracted signal pulses are measured to have durations of 10.6
      ps. Further, from the experimentally measured transmission data at 1064 nm, we
      have estimated the two-photon absorption coefficient of CSP to be beta=2.4 cm/GW,
      with a corresponding energy bandgap, E(g)=2.08 eV.

PMID- 21847222
TI  - High-order FDTD methods for transverse electromagnetic systems in dispersive
      inhomogeneous media.
AB  - This Letter introduces a novel finite-difference time-domain (FDTD) formulation
      for solving transverse electromagnetic systems in dispersive media. Based on the
      auxiliary differential equation approach, the Debye dispersion model is coupled
      with Maxwell's equations to derive a supplementary ordinary differential equation
      for describing the regularity changes in electromagnetic fields at the dispersive
      interface. The resulting time-dependent jump conditions are rigorously enforced
      in the FDTD discretization by means of the matched interface and boundary scheme.
      High-order convergences are numerically achieved for the first time in the
      literature in the FDTD simulations of dispersive inhomogeneous media.

PMID- 21847221
TI  - Carrier envelope phase stabilization of a Yb:KGW laser amplifier.
AB  - In this paper we report on the active stabilization of the carrier envelope phase
      (CEP) of a Yb:KGW chirped pulse amplifier laser system seeded by a Yb-doped solid
      state Kerr-lens mode-locked oscillator. The regenerative amplifier delivers 180
      fs CEP stable pulses of 30 MUJ-1 mJ energy at a repetition rate tunable from 1 to
      200 kHz. The bandwidth of the feedback loop was extended by a factor of 5 using a
      specially designed high-pass filter, which resulted in a dramatic decrease of CEP
      jitter below 0.45 rad after the amplifier.

PMID- 21847220
TI  - Noninvasive spectral imaging of skin chromophores based on multiple regression
      analysis aided by Monte Carlo simulation.
AB  - In order to visualize melanin and blood concentrations and oxygen saturation in
      human skin tissue, a simple imaging technique based on multispectral diffuse
      reflectance images acquired at six wavelengths (500, 520, 540, 560, 580 and 600
      nm) was developed. The technique utilizes multiple regression analysis aided by
      Monte Carlo simulation for diffuse reflectance spectra. Using the absorbance
      spectrum as a response variable and the extinction coefficients of melanin,
      oxygenated hemoglobin, and deoxygenated hemoglobin as predictor variables,
      multiple regression analysis provides regression coefficients. Concentrations of
      melanin and total blood are then determined from the regression coefficients
      using conversion vectors that are deduced numerically in advance, while oxygen
      saturation is obtained directly from the regression coefficients. Experiments
      with a tissue-like agar gel phantom validated the method. In vivo experiments
      with human skin of the human hand during upper limb occlusion and of the inner
      forearm exposed to UV irradiation demonstrated the ability of the method to
      evaluate physiological reactions of human skin tissue.

PMID- 21847223
TI  - Photonic Bloch oscillations of correlated particles.
AB  - A photonic realization of Bloch oscillations (BOs) of two correlated electrons
      that move on a one-dimensional periodic lattice, based on spatial light transport
      in a square waveguide array with a defect line, is theoretically proposed. The
      signature of correlated BOs, such as frequency doubling of the oscillation
      frequency induced by particle interaction, can be simply visualized by monitoring
      the spatial path followed by an optical beam that excites the array near the
      defect line.

PMID- 21847225
TI  - Single-shot polarization-imaging digital holography based on simultaneous phase
      shifting interferometry.
AB  - We propose single-shot digital holography which is capable of simultaneously
      capturing both the information of multiple phase-shifted holograms and the
      distribution of the polarization. In this technique, a single image sensor
      records both the information required for phase-shifting interferometry and that
      of the polarization states of objects using an array of polarizers. The essence
      of the technique is the capability of imaging the distribution of the
      polarization of three-dimensional objects with a single-shot exposure by using
      the space-division multiplexing of holograms. The validity of the proposed
      technique was confirmed by the preliminary experiments.

PMID- 21847224
TI  - Optomechanical spectroscopy with broadband interferometric and quantum cascade
      laser sources.
AB  - The spectral tunability of semiconductor-metal multilayer structures can provide
      a channel for the conversion of light into useful mechanical actuation. Responses
      of suspended silicon, silicon nitride, chromium, gold, and aluminum
      microstructures are shown to be utilized as a detector for visible and IR
      spectroscopy. Both dispersive and interferometric approaches are investigated to
      delineate the potential use of the structures in spatially resolved spectroscopy
      and spectrally resolved microscopy. The thermoplasmonic, spectral absorption,
      interference effects, and the associated energy deposition that contributes to
      the mechanical response are discussed to describe the potential of optomechanical
      detection in future integrated spectrometers.

PMID- 21847226
TI  - Degenerate band edges in optical fiber with multiple grating: efficient coupling
      to slow light.
AB  - Degenerate band edges (DBEs) of a photonic bandgap have the form (omega-omega(D))
      ?k(2m) for integers m>1, with omega(D) the frequency at the band edge. We show
      theoretically that DBEs lead to efficient coupling into slow-light modes without
      a transition region, and that the field strength in the slow mode can far exceed
      that in the incoming medium. A method is proposed to create a DBE of arbitrary
      order m by coupling m optical modes with multiple superimposed gratings. The
      enhanced coupling near a DBE occurs because of the presence of one or more
      evanescent modes, which are absent at conventional quadratic band edges. We
      furthermore show that the coupling can be increased or suppressed by varying the
      number of excited evanescent waves.

PMID- 21847227
TI  - Ultralow phase noise microwave generation with an Er:fiber-based optical
      frequency divider.
AB  - We present an optical frequency divider based on a 200 MHz repetition rate
      Er:fiber mode-locked laser that, when locked to a stable optical frequency
      reference, generates microwave signals with absolute phase noise that is equal to
      or better than cryogenic microwave oscillators. At 1 Hz offset from a 10 GHz
      carrier, the phase noise is below -100 dBc/Hz, limited by the optical reference.
      For offset frequencies >10 kHz, the phase noise is shot noise limited at -145
      dBc/Hz. An analysis of the contribution of the residual noise from the Er:fiber
      optical frequency divider is also presented.

PMID- 21847229
TI  - Third-harmonic generation via nonlinear Raman-Nath diffraction in nonlinear
      photonic crystal.
AB  - We report on the observation of multiple third-harmonic conical waves generated
      in an annular periodically poled nonlinear photonic crystal. We show that the
      conical beams are formed as a result of the cascading effect involving two
      parametric processes that satisfy either the transverse and/or longitudinal phase
      patching conditions. This is the first experimental observation of third-harmonic
      generation based on nonlinear Raman-Nath diffraction.

PMID- 21847228
TI  - Spectroscopic characterization and laser performance of resonantly diode-pumped
      Er(3+)-doped disordered NaY(WO4)2.
AB  - We report what is believed to be the first resonantly pumped laser operation
      based on Er(3+)-doped disordered double tungstate single crystal. Efficient laser
      operation of an Er(3+):NaY(WO(4))(2) laser at ~1609.6 nm was demonstrated with
      the naturally wideband, ~20 nm, InGaAsP/InP laser diode pumping at ~1501 nm.
      Laser wavelength tunability of ~34 nm was also demonstrated based on disorder
      broadened emission features of Er(3+):NaY(WO(4))(2) single crystal.

PMID- 21847230
TI  - Multilayer thin-film inspection through measurements of reflection coefficients.
AB  - A vibration-insensitive interferometer is described to measure the thickness,
      refraction index and surface profile of thin-film stack at normal incidence. By
      satisfying the continuous boundary conditions of electric and magnetic fields at
      interfaces in a multilayer film stack, the reflection coefficient phase of the
      thin-film stack can be distinguished from the phase of spatial path difference,
      thus thickness and refraction index can be extracted. The experiment results
      showed that the measurement precision is significantly increased after the phase
      analysis was added into the reflectance analysis.

PMID- 21847231
TI  - All-optically controlled concurrent slow-fast light pair.
AB  - We demonstrate how both normal and anomalous dispersion can be realized
      concurrently for a pair of weak probes in a doubly driven double-ladder
      configuration with independent and simultaneous control for group velocities of
      the pair. We have shown both analytically and numerically that, because of
      electromagnetically induced transparency and a chi((3))-based gain process, a
      slow-fast light pair can be realized in the same delay element with group indices
      ~+/-10(7) accompanied by gain or relatively small absorption (down to ~25%). We
      also identify parameter regions for realization of concurrent slow-slow and fast
      fast light pairs with reduced absorptions.

PMID- 21847232
TI  - Optofluidic microchannels in aerogel.
AB  - We report optofluidic waveguides made by filling microchannels in aerogel with
      water. The aerogel cladding is a nanoporous material with an extremely low
      refractive index of ~1.05, giving a large index step from the water core.
      Channels were formed by removing embedded optical fibers, which could be
      nonuniform or multiple. The porosity of the aerogel allowed air to be displaced
      from the channel, preventing the trapping of bubbles. The attenuation of red
      light in the highly multimode water core waveguide was no greater than 1.5 dB/cm.

PMID- 21847233
TI  - Thermal optimization and erasing of Nd:YAG proton beam written waveguides.
AB  - We report on how the optical and structural properties of Nd:YAG proton beam
      written waveguides are modified when they experienced annealing treatments from
      50  degrees C to 950  degrees C. The microstructural changes caused in the
      vicinity of the nuclear damage region were found to be stable up to 700  degrees
      C, so that higher annealing temperatures lead to a complete waveguide erasing.
      Before this "erasing" temperature, the partial thermal-induced defect
      recombination reduces the propagation losses, reaching its minimum value (below 1
      dB/cm) after a 400  degrees C thermal annealing.

PMID- 21847234
TI  - Experimental study of the focusing properties of a Gaussian Schell-model vortex
      beam.
AB  - We carry out an experimental and theoretical study of the focusing properties of
      a Gaussian Schell-model (GSM) vortex beam. It is found that we can shape the beam
      profile of the focused GSM vortex beam by varying its initial spatial coherence
      width. Focused dark hollow, flat-topped, and Gaussian beam spots can be obtained
      in our experiment, which will be useful for trapping particles. The experimental
      results agree well with the theoretical results.

PMID- 21847235
TI  - Potential mapping of optical tweezers.
AB  - Optical tweezers are very often used for measurement of piconewton range forces.
      Depending on the displacement of the trapped bead, the trap may become stiffer
      which causes considerable underestimation of the measured force. We have shown,
      both by theory and experiment, that such a stiffening occurs for beads larger
      than 0.5 MUm in radius. For the first time, we have shown that the displacement
      at which the stiffening starts is size dependent and that the stiffening starts
      at higher forces for larger beads. We have shown that for the applications, which
      simultaneous force measurement and position sensing are on demand (such as
      biopolymer stretching), mid-range sized (~1.5 MUm in radius) beads could be the
      best choice.

PMID- 21847236
TI  - Phase singularity of surface plasmon polaritons generated by optical vortices.
AB  - We demonstrate an experimental result that shows the phase singularity of surface
      plasmon waves generated by the direct transform of optical vortices at normal
      incidence focused on a structureless metal surface. The near-field two
      dimensional intensity distribution near the focal plane is experimentally
      examined by using near-field scanning optical microscopy and shows a good
      agreement with the finite-difference time-domain simulation result. The
      experimental realization demonstrates a potential of the proposed excitation
      scheme to be reconfigured locally with advantages over structures milled into
      optically thick metallic films for plasmonics applications involving plasmonic
      vortices.

PMID- 21847237
TI  - Gray solitons in parity-time symmetric potentials.
AB  - We numerically study the gray solitons in parity-time (PT) symmetric potentials.
      Simulated results show that there are two kinds of gray solitons, the dip-shaped
      gray solitons and the hump-shaped solitons, and both of them can be stable. Hump
      shaped solitons can always exist, but the grayness of a stable dip-shaped gray
      soliton should exceed a threshold value. More interesting, it is discovered that
      when propagating in PT symmetric potentials, the gray solitons have no transverse
      deviation, and this is a phenomenon different from the usual gray solitons.

PMID- 21847238
TI  - Two-dimensional guided mode resonance filters fabricated in a uniform low-index
      material system.
AB  - We demonstrate the fabrication, simulation, and experimental results of a buried,
      homogeneous narrowband spectral filter with a periodic, hexagonal unit cell of
      air pockets, encapsulated in a fused silica substrate. The leaky waveguide is
      formed by depositing SiO(x) on an etched fused silica grating via plasma-enhanced
      chemical vapor deposition. Design principles of guided mode resonance filters
      were utilized to achieve a resonance with 60% reflectivity at a wavelength of
      1.741 MUm. The device demonstrates resonance with FWHM of 6 nm.

PMID- 21847239
TI  - Partially liquid-filled hollow-core photonic crystal fiber polarizer.
AB  - A compact fiber polarizer is demonstrated by the filling of selected air holes of
      a hollow-core photonic crystal fiber (PCF) with a liquid. The liquid-filling
      results in an asymmetric waveguide structure, leading to a large polarization
      dependent loss. A 6 mm long ethanol-filled PCF exhibits a polarization extinction
      ratio of ~18 dB over a wavelength range from 1480 nm to 1600 nm.

PMID- 21847240
TI  - Lasing from Escherichia coli bacteria genetically programmed to express green
      fluorescent protein.
AB  - We report on lasing action from colonies of Escherichia coli bacteria that are
      genetically programmed to synthesize the green fluorescent protein (GFP). When
      embedded in a Fabry-Perot type cavity and excited by ns-pulses of blue light (465
      nm), the bacteria generate green laser emission (~520 nm). Broad illumination of
      pump light yields simultaneous lasing over a large area in bacterial colonies.

PMID- 21847241
TI  - Fluorescence ghost imaging with pseudothermal light.
AB  - We extend classical light ghost imaging to the area of fluorescence imaging and
      propose a new fluorescence imaging method. For the first time, we demonstrate
      both theoretically and experimentally that fluorescence ghost imaging can be
      realized with pseudothermal light. Important factors influencing the visibility
      and resolution of the images are discussed to improve the quality of the
      fluorescence ghost imaging. We hope that this work may pave the road for ghost
      imaging to biomedical applications.

PMID- 21847243
TI  - 25 years of Indian journal of psychiatry.

PMID- 21847244
TI  - Mental health limits, priorities and psychoethics.

PMID- 21847242
TI  - MaizeGDB becomes 'sequence-centric'.
AB  - MaizeGDB is the maize research community's central repository for genetic and
      genomic information about the crop plant and research model Zea mays ssp. mays.
      The MaizeGDB team endeavors to meet research needs as they evolve based on
      researcher feedback and guidance. Recent work has focused on better integrating
      existing data with sequence information as it becomes available for the B73, Mo17
      and Palomero Toluqueno genomes. Major endeavors along these lines include the
      implementation of a genome browser to graphically represent genome sequences;
      implementation of POPcorn, a portal ancillary to MaizeGDB that offers access to
      independent maize projects and will allow BLAST similarity searches of
      participating projects' data sets from a single point; and a joint
      MaizeGDB/PlantGDB project to involve the maize community in genome annotation. In
      addition to summarizing recent achievements and future plans, this article also
      discusses specific examples of community involvement in setting priorities and
      design aspects of MaizeGDB, which should be of interest to other database and
      resource providers seeking to better engage their users. MaizeGDB is accessible
      online at http://www.maizegdb.org.Database URL:http://www.maizegdb.org.

PMID- 21847245
TI  - In pursuit of happiness.

PMID- 21847246
TI  - Research in psychiatric genetics in India.

PMID- 21847247
TI  - The use of carbamazepine in patients with manic depressive illness.
AB  - 16 cases of affective disorder were studied. 8 patients received carbamazepine
      and 8 received either chlorpromazine or imipramine. Ratings were carried out on
      the Hamilton Rating Scale for Depression, Bech Rafaelsen Mania Rating scale and a
      side-effects symptom check list. Garbamazepine was found to be an effective
      treatment for affective disorders, possessing both anti-manic as well as anti
      depressant properties.

PMID- 21847248
TI  - Treatment of 26 cases of male sexual dysfunction by behaviour modification
      techniques.
AB  - 26 married males with premature ejaculation and secondary impotence were
      subjected to behavior therapy. Relaxation, graded tasks, semans exercise, the
      squeeze technique, desensitization and thought stopping were the techniques
      employed. 15 (58%) of the patients improved. Factors contributing to success or
      failure are studied and the results compared with those of others using Behaviour
      Therapy.

PMID- 21847249
TI  - The relationships of plasma and erythrocyte sodium, potassium and lithium in
      lithium prophylaxis.
AB  - The relationship of intracellular Na+ K+ Li+ to their extracellular
      concentrations had been studied on 22 cases bipolar affective disorders who had
      been on prophylactic lithium. 6 of these cases were nonresponders who were
      admitted repeatedly despite a therapeutic serum lithium values of 0.8-1.1 m
      moi/L. Parameters measured were Plasma lithium (Lp), Erythrocyte Lithium (Le),
      Plasma potassium (Kp), Erythrocyte potassium, Ke) Plasma sodium (Nae). Eli had
      been calculated by using Nerst's equation. Significant correlations have been
      obtained for dosage and Lp, Lp and Le, and Lp and Le/Lp. There were no
      significant difference between the responders and non-responders as regards to
      values of Le, Lp, Nap, Nae, Kp and Ke.

PMID- 21847250
TI  - Psychiatric problems of afghan refugees in delhi : a study on 152 outpatients.
AB  - A brief review of literature on psychiatric morbidity associated with migration
      is presented, with particular emphasis on the problems of political refugees.
      Initial experiences with 152 Afghan nationals attending the psychiatric
      outpatient department of a general hospital in Delhi during a period of 18 months
      are described supported by retrospective data from the records. Problems
      encountered in adequate assessment and management of these patients are
      highlighted. Need for prospective and longitudinal research on this group of
      patients is pointed out.

PMID- 21847251
TI  - A repertory grid comparison of endogenous and neurotic depressions.
AB  - The Repertory Grid Technique was used to study the construct systems of patients
      diagnosed as Endogenous and Neurotic Depressions. Twenty-five patients of each
      category were administered a Rank Order Repertory Grid comprising ten elements
      and fifteen constructs. The completed matrices were subjected to principal
      component analysis. Inter-element distance was used as the psychological measure
      to compare the two groups on characteristics like sell-ideal congruence, self
      esteem, self-criticalness, degree of identification with parents, and the degree
      of temperamental and/or personality differences between parents as perceived by
      them. No significant differences between the two categories emerged on any of the
      dimensions referred to above. One striking observation in many grids was a
      tendency to isolate the element 'self'. Another observation was the difficulties
      some subjects had with a few elements and constructs probably due to cultural
      factors.

PMID- 21847252
TI  - Obessive compulsive behaviours - a therapeutic study with thought stopping
      procedure.
AB  - In a Cross over design, the therapeutic value of thought-stopping technique in
      Obsessive Compulsive behaviour was examined by comparing its effect to that of
      progressive muscular relaxation. A group of 17 individuals with obsessive
      compulsive behaviours patterns served as study group. The measure of therapeutic
      change include frequency of obsession, Taylor's Manifest Anxiety scale, Beck's
      inventory for Depression. Distress rating and Fear survey schedule. The results
      showed marked improvement in 11 individuals and minimal improvement in 3 and no
      change in the remaining 3 individuals. Both relaxation and as thought stopping
      effected changes in the indices of therapeutic change. However, thought stopping
      was found to be significantly more effective. The study also discusses some
      follow-up data as well as the theoretical issues of obsessional behaviour.

PMID- 21847253
TI  - Development of a suicidal intent questionnaire.

PMID- 21847254
TI  - Child psychiatry in India - a Western view.

PMID- 21847255
TI  - Effect of lithium on serum electrolytes.
AB  - 26 patients diagnosed as manic depressive psychosis were treated with lithium for
      three months and serum levels of calcium, magnesium, phosphates and proteins were
      estimated repeatedly. There were no significant changes in the levels of these
      electrolytes and proteins during the three months of study period.

PMID- 21847256
TI  - Marital life and anxiety : implications for mental health professionals.
AB  - The marital life situations of the anxiety patients are compared with that of
      normals based on four important dimensions- partner's behaviour as perceived by
      the subject during his/her difficulties, difference of opinion in domestic
      management, criticism regarding their In-laws and threats of divorce. For this
      purpose, 20 Anxiety patients and 40 Normals based on group matching were studied.
      The implications for mental health professional's role functioning in dealing
      with the marital difficulties of anxiety neurotics are discussed.

PMID- 21847258
TI  - "Folie a deux" in identical twin sisters.

PMID- 21847257
TI  - Psychiatric manifestations of cystecercosis : review of literature and case
      report.
AB  - This article describes the report of a case of cerebral cystecercosis, diagnosed
      only after G. T. head scan, who presented primarily with a picture of an organic
      psychotic condition. The literature in relation to psychiatric aspects of
      cystecercosis is reviewed.

PMID- 21847259
TI  - Thiamine refractory-wernicke-korsakoffs syndrome - a case report.
AB  - A case of Thiamine refractory Wernicke-Korsakoff syndrome, successfully treated
      with the combination of magnesium sulphate and thiamine is presented. The role of
      Magnesium Sulphate in such cases has been discussed.

PMID- 21847261
TI  - Age of biological markers.

PMID- 21847260
TI  - Treatment of mania with carbamazepine and lithium.
AB  - A young manic patient who showed poor response to lithium, neuroleptics and ECT
      and developed severe cxtrapyramidal side effects restricting the use of
      neuroleptics in high doses; showed marked clinical improvement with a combination
      of carbamazepine and lithium with sustained recovery. The case reported to
      illustrate the possible synergistic action suggested earlier, encouraging the
      authors to take up a crossover trial.

PMID- 21847262
TI  - A study of side effects of lithium.
AB  - The present report is a study on the side effects experienced by the patients
      attending the Lithium Clinic of the Institute of Psychiatry, Government Rajaji
      Hospital, Madurai. Out of the 120 (M 78, F42) patients studied, 97 had side
      effects. The effects were examined in respect of their frequency, time of onset
      and course, their relation to one dose and serum levels of lithium and to the
      clinical response. The duration of therapy ranged from 3 months to 6 years.The
      most frequent side effects were tremors (26.6%) and polyuria (20.8%). The side
      effects occurred at varying periods from the onset of therapy. During the first 3
      months, tremors, excess salivation, nausea and abdominal discomfort; weight gain,
      memory defects and polyuria, between 3 months and 1 year; and hypothyroidism,
      tardive dyskinesia, acne and hair fall beyond one year.

PMID- 21847263
TI  - Utility of some genetic marker in predicting response to lithium.
AB  - One hundred manic patients who were treated with lithium were studied to find out
      the possibility of genetic variations in response to lithium. Along with pedigree
      study, test of colour blindness and ABO blood grouping were used as genetic
      markers. The study supports the transmission by autosomal dominance with
      incomplete penetrance. There is no difference between the responders and non
      responders in the mode of transmission and in the family history of mental
      illness, ABO blood grouping.

PMID- 21847264
TI  - Effects of long-term lithium carbonate treatment on thyroid function in
      psychiatric patients.
AB  - The effect of long-term lithium carbonate treatment on thyroid function was
      investigated in 40 clinically euthyroid patients with Manic Depressive Psychosis.
      Before lithium treatment, all patients showed normal levels (T(4)) of serum total
      thyroxine, free thyroxine index and thyrotropin (TSH). After lithium carbonate
      treatment for a mean period of 24 months, these patients did not show any
      significant change in the mean values of serum total T(4), free thyroxine index
      and TSH. None showed clinical symptoms of goitre and hypothyroidism after long
      term lithium treatment. It is concluded that lithium therapy in euthyroid
      psychiatric patients has no adverse effect on thyroid function and en the
      pituitary secretion of TSH.

PMID- 21847265
TI  - Effect of chronic administration of lithium on memory functions of rats.

PMID- 21847266
TI  - Lithium in aggression.
AB  - Aggression is psychological and social menace. The safety of the patient as well
      as other members of the society is jeopardised due to severe acts of aggression.
      Hence control of aggressive behaviour gets a priority over various other
      symptoms. Various treatment modalities have been tried to control the act of
      aggression. We carried out this study to find out antiaggressive effect of
      lithium carbonate. Twenty resistant patients of varied psychiatric diagnosis
      showing aggressive behaviour completed this six weeks outdoor trial. They were
      started on lithium after initial assessment and were called once a week for
      evaluation with their relatives for total period of six weeks. Their lithium dose
      w,s adjusted and they were assessed on an aggression scale. We found clinical
      improvement in seventy percent of our cases. Our conclusion was that lithium has
      a definite role in controlling aggression.

PMID- 21847267
TI  - An epidemiological study of prevalence of depressive illness in rural punjab.

PMID- 21847268
TI  - Prognosis of depression.
AB  - Relationship of different symptoms, personal history, some measures of Rorschach,
      neuroticism, ego strength score with prognosis of depression was studied. Out of
      60 items studied in 60 cases, eleven were found to have statistically significant
      association with improvement. Multiple regression of percentage of improvement on
      23 items (12 from personal and family history and 13 measurable items of
      Rorschach) was determined. To check the ability of this multiple regression to
      expl. in differences in responsiveness, predicted values were obtained for 24-
      cases (not included in the previous regression analysis). In most cases
      considerable differences was found in observed and predicted values. Then a
      regression coefficient using only 12 items (other than 13 Rorschach items) was
      determined similarly. Using this regression equation, predicted Values for
      percentage of improvement was obtained for the same 24 cases. There was
      insignificant association between observed and predicted Values. Thereafter only
      five measurable characteristics strongly related with percentage of improvement
      were taken and multiple regression on these items was determined and checked
      similarly on the same 24- cases. This also showed insignificant association
      between observed and predicted Values. Linear regression is unable to explain the
      difference in prognosis of population very similar to one on which it was
      developed. Inclusion of more history and social interaction factors might lead to
      more fruitful results.

PMID- 21847269
TI  - Suicidal communication in psychiatric patients.
AB  - In this enquiry a cross-sectional study of hospitalized psychiatric patients was
      undertaken to assess prevalence and nature of suicidal behaviour. We have been
      able to delineate these subjects into three categories i.e. non-communicators,
      partial communicators and definite communicators on the basis of their scores
      upon 31ucid.il intent questionnaire. A follow up study of these patients which is
      in progress may further provide knowledge about relationship between predictive
      criterion and their final outcome.

PMID- 21847270
TI  - Stressful life events in psychiatric outpatients : a controlled study.
AB  - The present study was conducted to investigate the frequency and types of life
      events experienced by psychiatric outpatients and to compare these with the
      events experienced by a control sample consisting of their normal relatives. One
      hundred and sixty-six patients and an equal number of marked controls were
      studied. Semi-structured interviews were conducted with the help of an event
      list. Results showed that; the patients experienced a significantly higher number
      of events compared to matched controls in previous one year. Desirable as well as
      undesirable events in all areas of life functioning were experienced more
      frequently by patients. Results are discussed in the light of existing
      information and suggestions offered for use of suitable methodology for further
      studies in this area.

PMID- 21847272
TI  - An epidemic of koro in west bengal (India).
AB  - An epidemic of Koro which occured in West Bengal has been described. Theories for
      the genesis of Koro as epidemic have been discussed. It has been shown that the
      present epidemic was related to social tensions.

PMID- 21847271
TI  - Metoclopramide in tardive dyskinesia.
AB  - The effect of single intravenous doses of metoclopramide (10 mg, 20 mg and 40 mg)
      have been compared with placebo (saline) in a double blind randomised study in 10
      patients with tardive dyskinesia following long term neuroleptic therapy. Tardive
      dyskinesia rating scores were decreased significantly (P<0.01) 6 hours after
      administration of metoclopramide 20 mg and 40 mg when compared with placebo.
      Reduction of tardive dyskinesia by metoclopramide-a D(2)receptor blocking agent
      suggest that D(2)receptors may be involved in the mediation of this syndrome.

PMID- 21847273
TI  - Is alopecia areata psychosomatic ?
AB  - Thirty cases of alopecia Areata from O.P.D. of Govt. Hospital, Madras were
      administered Indian Version of schedule of Recent Experience, Taylor's Manifest
      Anxiety Scale, Beck's Depressive Inventory, Hostility Direction and Hostility
      Questionnaire of Fould's and Cattell's 16 PF Questionnaire (Form E) to find out
      antecedent stress, anxiety, depression, hostility and personality factors. Thirty
      cases of Tinea versicolor as well as normal controls matched for age, sex,
      educational level and income were assessed on similar parameters. There was
      significant difference in the area of antecedent stress, anxiety and depression
      in Alopecia Areata group when compared to normal controls, Otherwise no
      Significant antecedent stress, anxiety, depression, hostility and personality
      factors could not be demonstrated in cases of Alopecia Areata as compared to a
      known non-psychosomatic illness i.e. Tinea-versicolor.

PMID- 21847274
TI  - Effects of relaxation therapy in management of muscular contraction headache in
      executives.
AB  - Five executives suffering from muscular contractions (tension) headache were
      treated by deep muscular relaxation therapy. Individual sessions were
      supplemented by practice of relaxation at home, brief relaxation, and cue
      relaxation during office hours.The effect of therapy, was assessed, by comparing
      the baseline, pretreatment individual assessment of their behavioral state and
      self report, with the similar assessment done during and after the successful
      completion of therapy. The advantages of such an individual assessment & self
      report in the management of muscular contraction headache are discussed.

PMID- 21847275
TI  - A study of experienced reality of auditory hallucinations in schizopherenics.
AB  - 30 Schizophrenics having verbal auditory hallucinations and satisfying the
      criteria of Feighner et al. (1972) were examined for the experienced reality of
      auditory hallucinations and the influence of certain variables on such reality.
      Number of hallucinating days per month, fast movement of time during
      hallucination, presence of running commentary voices, interference in self-care
      and social activities due to the Voices and degree of success in manipulation and
      avoidance (coping themes) appreciably influenced the experienced reality. The
      voices were more real than unreal.

PMID- 21847276
TI  - A clinical study of trifluperazine vs trifluperazine benzhexol combination.

PMID- 21847278
TI  - A case of frotteurism and its successful treatment by behaviour therapy.

PMID- 21847277
TI  - Capgras' syndrome and cerebral dysfunction.

PMID- 21847279
TI  - Schizophrenia associated with retinitis pigmentosa : a case report.

PMID- 21847280
TI  - Family and psychiatry.

PMID- 21847281
TI  - Urinary melatonin in depression.
AB  - This report is based on a study of 12 cases of depression (8 endogenous, 4
      neurotic) with a view to explore the possible association between urinary
      melatonin and the illness prior to and following treatment. While cases of
      endogenous depression had low 24 hour as well as nocturnal urinary melatonin
      levels, the neurotic depressives showed higher than normal levels. A rise in the
      24 hour melatonin levels occurred in all cases of endogenous depression though
      this did not apply, to the nocturnal levels. An association between melatonin
      levels with suicide behaviour, insomnia, psychomotor retardation and diurnal
      variation is discussed.

PMID- 21847282
TI  - Psychiatric aspects of chronic intractable pain.
AB  - Two hundred patients with chronic intractable pain have been evaluated in order
      to study the clinical characteristics of pain and associated psychiatric
      illnesses. The commonest site of pain was reported to be head and face, usually
      dull in nature. Almost 75% of patients reported continuous pain. A great majority
      (40%-80%) had some psycho-social problem or other problem resultant from the
      chronic pain. 72% patients had identifiable psychiatric illness, commonest being
      neurotic depression and anxiety states. The common symptoms reported on the
      Present State Examination (PSE) were worrying (77%), depression (40%),
      hypochondrical pre-occupation (35%), autonomic anxiety (42%) and irritability
      (40%). There is no specific clinical characteristic associated with any
      particular psychiatric diagnosis. The relevance of psychiatric symptoms and
      illness associated with chronic pain has been discussed.

PMID- 21847283
TI  - Institutionalised mentally retarded in a state mental hospital.
AB  - 298 institutionalised mentally retarded patients in Institute of Mental Health,
      Madras were studied for the aetiological factors, levels of intelligence,
      associated disorders and family structure and compared with 163 matched group of
      mentally retarded attending the outpatient services of the Institute of Mental
      Health. In 41% of the institutionalised the cause was unknown, 29.3% had
      infective aetiology, 18% formed the primary group and 6.4% were due to genetic
      and chromosomal factors. Statistically significant number of institutionalised
      were severely subnormal, had more associated disorders and poor family structure.
      The need for the development of exclusive residential services for the mentally
      retarded and community oriented approach are discussed.

PMID- 21847284
TI  - Affect of parental rejection on negative attention-seeking class room behaviors.
AB  - Of concern to teachers are students displaying classroom behaviors which are
      disruptive in attaining pupil success in learning and teacher success in
      teaching. The present study was conducted to determine the effect of parental
      rejection on negative attention-seeking classroom behaviors. It was also
      conducted to find out what particular parent might be more rejecting toward the
      respondents, and, what specific negative attention-seeking behaviors might be
      overtly demonstrated in the classroom by sex of subject. Results indicated a
      significant influence of parental rejection on negative attention-seeking
      classroom behaviors, the father as a more rejecting parent, and differences in
      observed behaviors by sex of subject.

PMID- 21847285
TI  - Neurosis and sexual behaviour in men.
AB  - Relationship of neurosis and sexual behaviour has been a matter of dispute till
      date. In the present study sexual behaviour of 40 married neurotics and 22
      matched healthy control males was studied. Sexual behaviour of neurotics was
      similar to control subjects before the commencement of neurotic illness. But
      after the onset of the neurotic illness subjects showed significant decrease in
      frequency of coitus, sexual satisfaction and sexual adequacy in comparison to
      their pre illness behaviour as well as from healthy controls.

PMID- 21847286
TI  - A psychiatric study of cases attending dental o.p.d of a teaching general
      hospital.
AB  - One hundred thirty cases were selected by systematic sampling from those
      attending the dental O.P.D. of a teaching general hospital, excluding those under
      14 years and those unable to read and write Hindi well. They were administered a
      questionnaire carrying 50 questions covering dental and non-dental (mainly
      psychiatric) symptoms and the Hindi version of Middlesex Hospital Questionnaire.
      After this they were seen by a dental surgeon and a psychiatrist separately.
      Nearly a quarter of the cases had no dental disease and only slightly less than
      half had a definite psychiatric illness. Dental O.P.D. cases scored significantly
      higher on the M.H.Q. as compared to normal controls. The younger patients had the
      maximum score of the OBS subscale while the older ones scored maximum on the
      D.F.P sub-scale. The number of symptoms complained of by the patients were
      directly related to their M.H.Q, scores.

PMID- 21847287
TI  - Suitability of a socio-economic scale for hospital psychiatric population.
AB  - The Socio-economic scale devised by Gupta and Sethi (1978) was applied to 737
      urban cases registered in the psychiatric out-patient department of a general
      hospital during the period of one year. Correlation and regression co-efficients
      were calculated for education, income, occupation and total scores. The scale
      seemed to be suitable for hospital psychiatric population.

PMID- 21847288
TI  - A study of prophylactic value of antiparkinsonian drug.
AB  - The present prospective study is conducted to determine the prophylactic value of
      antiparkinsonian drug (A.P.) at the time of initiation of antipsychotic therapy.
      Seventy patients were selected who fulfilled the selection criteria. Thirty five
      patients received antipsychotic drugs alone (Group A), while another thirty five
      patients received A.P. drugs concurrently with antipsychotic drugs (Group B.)
      These patients were assessed weekly for 4 weeks for any extra pyramidal symptoms
      (E.P.S.). There was no statistically significant difference between E.P.S. scores
      of the two groups in different weeks. The difference in percentage of patients
      who developed E.P.S. in different weeks in both the groups was statistically non
      significant (p<0.05). None of the female subjects developed E.P.S. in either
      group.

PMID- 21847289
TI  - E. C. T. And drug induced parkinsonism.
AB  - A cross-sectional evaluation of the presence of drug induced parkinsonian
      symptoms in hospitalized patients was done. Patients who had received two or more
      ECTs had lower scores of parkinsonism when compared to those who were net
      receiving ECT. Since the patient groups were comparable on parameters which would
      influence the occurrence and development of drug induced parkinsonism, the
      lowered scores in one group could be attributed to the effect of ECT.

PMID- 21847290
TI  - Psychiatric illness following childbirth a clinical study of 34 cases.
AB  - The study comprises of 34 cases, who developed psychiatric illness following
      childbirth. The diagnostic breakup reveals that 50% cases were of schizophrenia,
      35.4% of affective disorder, 11.7% of organic confusional state and 2.9% of
      hysteria. Age of the patients ranged from 17 to 35 years, average being 24.2
      years. 20.5% cases gave history of psychiatric illness in 1st degree relatives.
      All cases of organic psychosis, 41.6% of the affective disorder and 29.4% of the
      schizophrenia group had one or more of the physical complications during
      pregnancy, around delivery or during post-partum period. 25.2% of the cases had
      previous psychiatric illness following childbirth. 52.9% of the cases developed
      psychiatric illness in the 1st fortnight after delivery. The result of the
      treatment was highly satisfactory, showing improvement of all the patients
      included in this study.

PMID- 21847291
TI  - Psychiatric factors in ulcerative colitis.
AB  - Controlled study on 20 patients of ulcerative colitis was conducted at
      Gastroenterology Department of Civil Hospital, Ahmedabad. It has been observed
      that in three fourth of the cases, age of onset is before 40 years; & male,
      female ratio 4:1. No significant trend emerged in marital status, type of family,
      birth order, dietary habit and parental profile. The disease is common in lower
      socio-economic status. Ulcerative colitis patients are particularly exposed to
      stressful life situations and more prone to develop illness.

PMID- 21847292
TI  - Primidone in epilepsy-its value in fresh and refractory cases.

PMID- 21847293
TI  - Successful treatment of obsessive-compulsive disorder with zimelidine, a
      serotonin re-uptake inhibitor.
AB  - A 37 year old lady with severe obsessive-compulsive features which figured on
      Leyton's inventory was successfully treated with Zimelidine, a serotonin re
      uptake inhibitor. Her response was rapid and associated with improvement in her
      mood. Two months later, she had still not relapsed and was maintaining her
      improvement.

PMID- 21847294
TI  - Drug surveillance programme in psychiatry - adverse durg reactions.
AB  - In a clinically monitored surveillance of adverse drug reactions in a sample of
      186 indoor patients in a general hospital over an average hospital stay of about
      two weeks, the following points were noteworthy. 32.8% of the patients reported
      side-effects and of these 79.3% were of mild to moderate intensity.Side-effects
      could be easily managed by specific antidotes and reassurance and permitted
      continuation of the same medication.There was no association between side-effects
      and socio-demography or clinical characteristics of the patient. Side-effects
      fitted in with the pharmacological profiles of the drugs used. In only 7.3% of
      cases was major treatment change made after the occurrence of the side effect.
      Improvement was independent of side-effects and no unusual or toxic reactions
      were seen.

PMID- 21847295
TI  - Homesexuality - a study of treatment and outcome.
AB  - In the present study six homosexuals (5 males and 1 female) between 19 to 30
      years, were treated by double differential conditioning. Four of them achieved a
      sexual reorientation. However their attitudes, psychological sophistication,
      variables affecting the outcome and the problems experienced during therapy are
      discussed.

PMID- 21847296
TI  - Therapeutic compliance of patients on phenothiazines.
AB  - The present study was designed to assess the therapeutic compliance of
      psychiatric patients who reported to be on regular medication particularly
      phenothiazines. Of the all cases subjected to the F.P.N, test, it was clearly
      negative in 21 (18.9 %) indicating, their non-adherence to the drug therapy.
      Despite their report of regular drug intake at the time of urine screening, five
      of these twenty one patients had reported at a later date discontinuity of
      therapy for some reason or the other. Curiously, on a long term drug therapy, the
      incidence of non-compliance is relatively less.

PMID- 21847297
TI  - A report of subclinical psychological deterioration (a type of alcoholic
      dementia).
AB  - Alcoholics could present with various degrees of deterioration of cognitive
      functioning. The subclinical psychological deterioration had been one of the
      least recognized entities. This condition could be reversed or atleast arrested
      with treatment. The application of the term alcoholic dementia happened to be a
      misnomer for the clinical entity. A case of subclinical psychological
      deterioration that improved with treatment has been described here.

PMID- 21847298
TI  - Internal carotid artery thrombosis presenting as catatonic stupor - case report.

PMID- 21847299
TI  - Audiovisual AIDS in psychiatry.

PMID- 21847300
TI  - Depression and suicide behaviour in the aged.

PMID- 21847301
TI  - Depression in hypertensive subjects.
AB  - 168 patients attending hypertension clinic were randomly selected for the study.
      They were thoroughly investigated using E.C.G., X-ray chest, Urine analysis,
      Blood sugar, Blood urea, Serum cholesterol, Serum K, Serum Na, Scrum creatinine
      and Uric acid level. Detailed psychiatric case history and mental examination was
      carried out. Beck Rating Scale was used to measure the depression. 25% of
      hypertensive subjects exhibited depressive features and their mean score in Beck
      Rating scale is 21.76. The mean score of non-depressives is 4.46. All patients
      were receiving methyl dopa.25 mg. twice or thrice daily with thiazide diuretic.
      No significant difference in the incidence of depression with the duration of
      medication was observed.The hypertension was classified into mild, moderate and
      severe depending on the diastolic pressure. Depression was more frequent in
      severe hypertensives but not to the statistically significant level.Further
      hypertensives were classified into:1. Hypertension without organ involvement2.
      Hypertension with LVH only3. Hypertension with additional organ involvement4.
      Malignant hypertensionDepression was significantly more frequent in hypertensives
      with complications and also hypertensives in whom the B.P. remained uncontrolled.
      As all the patients were on the same drug, the drug effect is common to all;
      hence, the higher incidence of depression in hypertensives with complications is
      due to the limitation and distress caused by the illness.

PMID- 21847302
TI  - A study of attitudes of key relatives of schizopherenic patients.

PMID- 21847303
TI  - Drug and alcohol dependence : the past decade and future, view from a development
      country.

PMID- 21847304
TI  - Serological and biochemical genetic markers and their associations with
      psychiatric disorders : a review.
AB  - The studies pertaining to associations of serological and biochemical genetic
      markers (blood groups in particular and scrum proteins and enzymes in general)
      with the psychiatric disorders such as psychoses in general, Schizophrenia, manic
      depressive psychosis including unipolar and bipolar affective disorders and
      neuroses have been critically examined. The reasons for inconsistent findings of
      various investigators have been pointed out to assist the future researchers to
      overcome the previous drawbacks. Implications of associations of genetic markers
      with the psychiatric disorders have been discussed and future areas of research
      suggested.

PMID- 21847305
TI  - Suicidal ideation and biogenic amines in depression.
AB  - This report is based on the study of 40 depressives in an attempt to explore the
      possible association between the suicidal ideas and the biogenic amines. The
      severity of suicidal ideas was measured on Hamilton Depressive Rating Scale and
      their amine metabolites were measured (MHFG, HVA and 5 HIAA) in urine and C.S.F.
      It was observed that the level of 5 HIAA, and Serotonin (5 HT) was more related
      to suicidal ideas and was inversely related. The probable associations between
      these are discussed.

PMID- 21847306
TI  - Hospital stay of in-patients in a general hospital psychiatry unit.
AB  - This report examines the hospital stay of psychiatric in-patients in a general
      hospital psychiatric setting.The hospital stay days, psychiatric diagnosis,
      outcome, number of re-admission and some socio-demographic details of patients
      admitted during one year period were recorded and analysed. The mean hospital
      stay was 29.39 +/- 20.43 days. 60% patients stayed less than 4 weeks. The mean
      hospital stay of various categories was calculated. Schizophrenics 29.62 +/-
      25.82 days, manic depressives 35.29 +/- 33.04 days and neuroses 24.83+/-18.43
      days. Chronic Schizophrenics stayed longest (43.64+/-22.56) days. Of the
      Affective Psychosis group, between manics and depressives no difference was
      noticed. Good prognosis and relatively benign conditions had a briefer stay.
      Patients with no improvement stayed for significantly shorter- period (p< .001).
      Readmission cases tend to stay longer than fresh admissions (p< .05). The
      implications and interpretations especially in a general hospital psychiatric
      setting are discussed.

PMID- 21847307
TI  - Orientation course in psychiarty for the general practitioners.
AB  - A large proportion of clients of General practitioners suffer from psychiatric
      morbidity and they are either not identified at all or are only inadequately
      managed because their training in psychiatry at the undergraduate level is
      insufficient.The training of GPs in psychiatry economically in a short course,
      and evaluation of such training is a challenging task. Only recently some
      sporadic efforts are being made to develop and evolve training programmes in an
      increasingly thorough manner.A 20 weeks, once a week training programme for 30
      motivated GPs was conducted at NIMHANS, Bangalore in 1979-80. This training
      programme which was more thoroughly structured was based on the experiences from
      an earlier unstructured once a month, 2 year course conducted at Bangalore in
      1977-78.The results were not only encouraging but also highlighted a few
      challenging areas for further work.

PMID- 21847308
TI  - Comparison of three treatment regimes in schizophrenia.
AB  - 90 schizophrenic patients in three regimes of thirty patients each, were treated
      for a period of three weeks with haloperidol alone, E.C.T. alone and E.C.T. +
      haloperidol in combination respectively. Rating them on R. P. scale (Rockland and
      Pollin, 196a) & Disability Rating Scale (Gautam, 76) showed that the E.C.T. +
      haloperidol receiving group was significantly better on several measures on day 8
      & day 15 and also had an earlier onset of beneficial responses on "Affect & Mood"
      & on scores of "General appearance and behaviour". However, at the end of three
      weeks these differences disappeared and the three groups did not differ
      significantly.

PMID- 21847309
TI  - The treatment of insane patients in India in the lunatic asylums of the
      nineteenth century.

PMID- 21847310
TI  - Life events and course of a physical illness.
AB  - Sixty patients of pulmonary tuberculosis selected through a specified selection
      procedure were followed up after one year of treatment. The psychiatric
      assessment was done by Present State Examination (P.S.E.) brief version and an
      open ended life event questionnaire. Results indicate that the non-life event
      group patients improved significantly (p<0.001) more as compared to life event
      group patients. The findings are discussed in the light of available literature.

PMID- 21847311
TI  - Fountain house, lahore - a unique experiement in cross-cultural collaboration.
AB  - Fountain House has passed through various developmental stages. It has adopted
      the ideology of a club-house from Fountain House, New York, along with a number
      of innovative programmes for the rehabilitation of the mentally ill. Through a
      process of constant experimentation and evaluation, it has evolved a programme
      and an ideological framework which is in keeping with the religious and cultural
      requirements of the members served by Fountain House, Lahore.

PMID- 21847313
TI  - An elementary study of the principles of individual and group psychotherapy and
      mental health in islam.

PMID- 21847312
TI  - A study of inner voices in schizophernics.
AB  - Twelve schizophrenics with inner voices were examined and were compared to 12 -
      schizophrenics with external voices. The inner voices group was largely
      heterogenous. The inner voice group had shorter interval between onset of illness
      and onset of hallucinations, higher intensity of emotions outside the
      hallucinatory episodes but concerning the voices and longer duration of
      individual episodes of hallucinations.

PMID- 21847314
TI  - Toxic delirious state due to accidental ingestion of datura.
AB  - Four cases of toxic delirium resulting from accidental ingestion of datura seeds
      are reported. All of them had features of anticholinergic delirium.

PMID- 21847315
TI  - Graphics Processing Units and High-Dimensional Optimization.
AB  - This paper discusses the potential of graphics processing units (GPUs) in high
      dimensional optimization problems. A single GPU card with hundreds of arithmetic
      cores can be inserted in a personal computer and dramatically accelerates many
      statistical algorithms. To exploit these devices fully, optimization algorithms
      should reduce to multiple parallel tasks, each accessing a limited amount of
      data. These criteria favor EM and MM algorithms that separate parameters and
      data. To a lesser extent block relaxation and coordinate descent and ascent also
      qualify. We demonstrate the utility of GPUs in nonnegative matrix factorization,
      PET image reconstruction, and multidimensional scaling. Speedups of 100 fold can
      easily be attained. Over the next decade, GPUs will fundamentally alter the
      landscape of computational statistics. It is time for more statisticians to get
      on-board.

PMID- 21847316
TI  - AIAN guidelines for management of common neurological disorders.

PMID- 21847317
TI  - Treatment in late Parkinson's disease.

PMID- 21847318
TI  - Motor fluctuations and dyskinesias (diagnosis and management).

PMID- 21847319
TI  - Constipation in Parkinson's disease.

PMID- 21847320
TI  - Psychosis in Parkinson's disease.

PMID- 21847321
TI  - Assessment and management of orthostatic hypotension in Parkinson's disease.

PMID- 21847322
TI  - Sleep disorders in Parkinson's disease: Diagnosis and management.

PMID- 21847323
TI  - Parkinson's disease.

PMID- 21847324
TI  - Dementia in parkinsonism.

PMID- 21847325
TI  - Guidelines for management of essential tremor.

PMID- 21847326
TI  - Predictive genetic testing in Huntington's disease.

PMID- 21847327
TI  - Guidelines for the use of botulinum toxin in movement disorders and spasticity.

PMID- 21847328
TI  - Cerebral malaria and bacterial meningitis.

PMID- 21847329
TI  - Guidelines on the diagnosis and the current management of headache and related
      disorders.

PMID- 21847330
TI  - Initiation of treatment in early PD (evidences based).

PMID- 21847332
TI  - Treatment of multiple sclerosis.

PMID- 21847331
TI  - Acute disseminated encephalomyelitis: Treatment guidelines.

PMID- 21847333
TI  - Bell's palsy: Treatment guidelines.

PMID- 21847334
TI  - Treatment guidelines for Guillain-Barre Syndrome.

PMID- 21847336
TI  - Visual perception changes and optical stability after intracorneal ring segment
      implantation: comparison between 3 months and 1 year after surgery.
AB  - PURPOSE: To prospectively evaluate intracorneal ring segment (ICRS) implantation
      on quality of life (QoL) of patients with keratoconus changes and identify
      factors responsible. METHODS: Sixty-nine eyes of 42 keratoconus patients were
      implanted with the Keraring (Mediphacos, Belo Horizonte, Brazil). Best corrected
      visual acuity (BCVA), refraction, and steep keratometry were analyzed 3 months
      and 1 year after surgery. All patients self-administered the National Eye
      Institute Refractive Error Quality of life instrument at 2 time points: after
      having worn best correction for at least 30 days since evaluation (mean 4 months
      after surgery) and 1 year after surgery. To analyze if the use of the appropriate
      correction at 1 year follow up had any impact on visual acuity and V-QoL,
      patients were divided into 2 groups: group A (appropriate correction) and B (not
      appropriate correction). RESULTS: After 1 year, QoL changes related to scales
      'clarity of vision', 'near vision', and 'far vision'. Keratometric values,
      sphere, and spherical equivalent did not differ significantly between 3 months
      and 1 year postoperative. Cylinder increase was statistically but not clinically
      significant. Binocular BCVA did not change 1 year after surgery in group A and
      showed a clinically significant impairment in group B. A year after surgery, 18
      patients did not use correction suggested by a physician 3 months after surgery.
      QoL was not statistically different 1 year after surgery between group A and
      group B. CONCLUSION: Our findings show that the way keratoconic patients see is
      difficult to analyze using only quantitative and 1-visit metrics. They highlight
      the importance of patients' self perception and performing longitudinal analysis
      to consider neural compensation to optical changes from surgery.

PMID- 21847337
TI  - The first report on intermediate-term outcome of Ex-PRESS glaucoma filtration
      device implanted under scleral flap in Japanese patients.
AB  - PURPOSE: This paper compares the outcomes of the Ex-PRESS((r)) Glaucoma
      Filtration Device (Alcon, Fort Worth, TX) implant observed in Japanese patients
      for 1 year with those of patients undergoing trabeculectomy. PATIENTS AND
      METHODS: The subjects comprised ten eyes of ten cases with open-angle glaucoma
      for which filtration surgery using Ex-PRESS (P-50) was performed by one operator
      from February 2008 and observed for at least 1 year (Ex-PRESS Group), and eleven
      eyes of eleven cases for which trabeculectomy was performed by the same operator
      (TE Group). For both groups, mitomycin C was used and a scleral flap was created
      after a fornix-based incision of the conjunctiva. RESULTS: Hypotony and choroidal
      detachment were observed as early postoperative complications during a 1-week
      period in one-third of the cases in the TE Group, and failing vision in about
      45%, while these were seen in fewer cases in the Ex-PRESS Group. No significant
      difference in intraocular pressure (IOP) was observed during the period, but IOP
      variations on the day following the surgery were obviously narrower in the Ex
      PRESS Group than in the TE Group. Visual acuity was significantly poorer from 1
      week to 3 months in the TE Group while it was stable in the Ex-PRESS Group. The
      Ex-PRESS Group had fewer cases of laser suture lysis and fewer administrations of
      glaucoma eyedrop, and no cases of progression in the stage of visual field
      defect. CONCLUSION: Filtration surgery using the Ex-PRESS is unlikely to cause
      early complications in Japanese patients. Similarly to the trabeculectomy, the
      intermediate-term control of IOP showed favorable results.

PMID- 21847335
TI  - Stroke management.

PMID- 21847338
TI  - A case of recurrent bloody tears.
AB  - Well-known causes of blood-tinged epiphora are conjunctival lesions, tumors of
      the lacrimal apparatus, and systemic bleeding disorders. We describe an unusual
      patient who presented with recurrent episodes of bloody tearing which began
      following an erythema multiforme-like drug eruption. He experienced chronic
      conjunctivitis which resulted in a few minor symblephara. One year later, the
      patient developed attacks of bloody tearing. All clinical, radiologic, and
      laboratory investigations related to bloody epiphora were within normal limits
      except for a mild, nonspecific chronic inflammatory reaction in the perivascular
      tissues of the lacrimal gland and orbital soft tissues. Also, an increase in
      vascular permeability and contrast extravasation on carotid angiography was
      detected. High-dose vitamin C was administered. The patient continued to have
      unilateral bloody tears intermittently for two years, but the episodes became
      much less frequent and had resolved by three years. It is conceivable that
      increased vascular permeability following the systemic inflammatory process could
      have played a role in the etiology of recurrent bloody tears in this atypical
      patient.

PMID- 21847339
TI  - Comparison of Goldmann and Pascal tonometry in relation to corneal hysteresis and
      central corneal thickness in nonglaucomatous eyes.
AB  - OBJECTIVE: To compare measurements obtained by Goldmann applanation tonometry
      (GAT) and Pascal dynamic contour tonometry (DCT), and to study their relationship
      to corneal thickness and biomechanical properties in nonglaucomatous eyes.
      METHODS: This is a prospective and randomized study of 200 eyes from 200 non
      glaucomatous subjects who underwent intraocular pressure (IOP) measurements by
      GAT and DCT. The two methods were compared and assessed for agreement by means of
      the Bland-Altman plot. Central corneal thickness (CCT) and corneal hysteresis
      (CH) were obtained by ultrasound pachymeter and Ocular Response Analyzer,
      respectively. The effect of CH and CCT was correlated with the DCT/GAT IOP
      differences. RESULTS: Mean age was 57.4 +/- 14.7 years (range 24-82 years). Mean
      IOP measurements obtained were 16.7 +/- 3.2 mmHg by GAT and 19.4 +/- 3.3 mmHg by
      DCT. DCT showed a statistically significant higher mean IOP (2.7 +/- 1.9 mmHg, P
      < 0.001) compared with GAT. Mean CCT and CH were 546.5 +/- 40 MUm and 10.85 +/-
      2.0 mmHg, respectively. The differences in IOP (DCT - GAT) were significantly
      correlated with CCT and CH (Pearson's correlation coefficient r = -0.517 and 
      0.355, P < 0.0001, respectively). The difference between the two correlation
      coefficients was statistically significant (P < 0.05, Z-statistic). According to
      the Bland-Altman plot, the results of the two methods were clinically different.
      CONCLUSION: Significantly higher IOP readings were obtained by DCT than by GAT in
      nonglaucomatous subjects. The IOP differences between the two methods were
      associated with CCT and CH, suggesting that DCT was less dependent on corneal
      parameters. Each method provides clinically different IOP values, indicating that
      DCT and GAT should not be used interchangeably.

PMID- 21847340
TI  - Single intravitreal ranibizumab for myopic choroidal neovascularization.
AB  - We report a case of myopic choroidal neovascularization that showed improvement
      after a single injection of ranibizumab. A 45-year-old Chinese man with high
      myopia presented with sudden onset painless central scotoma of his right eye of 2
      weeks' duration. There was no history of trauma. His right eye vision on
      presentation was 6/30 which showed no improvement with pinhole. The right fundus
      showed myopic maculopathy at the posterior pole with subretinal hemorrhage at the
      inferotemporal fovea. The optic disc was tilted with inferotemporal peripapillary
      atrophy. There was a myopic maculopathy appearance in the macula of the left eye.
      Fundus fluorescein angiography revealed choroidal neovascularization at the fovea
      of the right eye. A diagnosis of right eye choroidal neovascularization secondary
      to myopic maculopathy was made. A single intravitreal injection of ranibizumab
      0.05 mL was given. Ten weeks following intravitreal injection, vision had
      improved to 6/7.5, and repeated fundus fluorescein angiography showed absence of
      choroidal neovascularization. Follow-up at 6 months showed visual acuity had
      normalized to 6/6 with glasses, which was maintained up to 12 months following
      treatment. The right fundus showed no further subretinal hemorrhage with no new
      lesions.

PMID- 21847341
TI  - Central retinal artery occlusion resembling Purtscher-like retinopathy.
AB  - This paper reports three cases of central retinal artery occlusion (CRAO) with
      Purtscher-like retinopathy and good recovery of visual function. The three cases
      of CRAO had similar fundus changes, ie, cotton wool patches surrounding the optic
      disc and whitening of the retina surrounding the fovea with a cherry red spot.
      Fluorescein angiography showed a delay of arm-to-retina circulation time and a
      partial defect of choroid circulation. Although the three cases were treated by
      different regimens of steroid pulse therapy and antiplatelet therapy, visual
      function recovered well and all disturbances of the retinal and choroid
      circulations resolved. Although eyes with a CRAO normally have a poor visual
      prognosis, our three cases responded well to the treatments and recovered good
      visual function. Thus, cases showing fundus changes similar to our three cases
      may have a pathogenesis different from that of a complete CRAO.

PMID- 21847342
TI  - Pars plana vitrectomy and internal limiting membrane peeling for macular edema
      secondary to retinal vein occlusion.
AB  - PURPOSE: To evaluate the effects of vitrectomy and internal limiting membrane
      peeling for treatment of macular edema secondary to retinal vein occlusion (RVO).
      METHODS: Nine cases of visual loss due to macular edema caused by central retinal
      vein occlusion or branch retinal vein occlusion underwent pars plana vitrectomy
      with removal of the preretinal hyaloid, peeling of the internal limiting membrane
      stained with indocyanine green dye, air-fluid exchange, and postoperative prone
      positioning. Best-corrected visual acuity (BCVA) and central foveal thickness by
      optical coherence tomography were measured pre- and postoperatively then compared
      to assess the outcome of surgery. RESULTS: In all cases intraretinal blood and
      retinal thickening diminished within 2 months of surgery. Visual acuity improved
      in all of the central retinal vein occlusion cases and 3/6 branch retinal vein
      occlusion cases. The decrease in macular thickness was statistically significant
      (mean postoperative macular thickness 361 +/- 61.1 versus mean preoperative
      macular thickness 563.9 +/- 90.0, P = 0.001, t-test). The improvement in BCVA was
      not statistically significant (mean preoperative BCVA in LogMAR 1.23 +/- 0.29
      versus mean postoperative BCVA in LogMAR 1.06 +/- 0.49, P = 0.09, t-test).
      CONCLUSION: In eyes with macular edema secondary to RVO, pars plana vitrectomy
      with internal limiting membrane peeling can resolve macular edema, but the
      improvement in BCVA was not statistically significant in this study.

PMID- 21847344
TI  - Current neoadjuvant treatment options for HER2-positive breast cancer.
AB  - Approximately one quarter of patients with breast cancer demonstrate
      amplification of the human epidermal receptor type 2 (HER2) gene, the expression
      of which is associated with a relatively poor prognosis independent of other
      clinical and pathologic variables. Trastuzumab, a humanized recombinant
      monoclonal antibody specifically directed against the HER2 receptor, has been
      shown to be biologically active and of considerable clinical utility in HER2
      positive breast cancer patients. Neoadjuvant chemotherapy has been used in breast
      cancer to downstage the tumor and increase the opportunity for breast-conserving
      surgery. Preoperative chemotherapy can also serve as an in vivo testing of
      chemotherapy sensitivity. Additionally, a pathologic complete response is usually
      a surrogate marker of disease-free survival. Following the successful use of
      trastuzumab in the metastatic and adjuvant settings, many clinical trials have
      recently reported the successful use of anti-HER2 therapy in combination with
      different chemotherapy regimens in the neoadjuvant setting with a significantly
      higher pathologic complete response. With the recent introduction of new anti
      HER2 drugs, interest has shifted toward dual HER2 blockade. Two such studies were
      recently reported, both showing a significant advantage of dual anti-HER2 therapy
      using lapatinib or pertuzumab in addition to trastuzumab and chemotherapy.
      However, several key questions need to be investigated further, such as the
      preferred combination chemotherapy and the optimal duration of trastuzumab in
      patients who achieve a pathologic complete response following preoperative
      chemotherapy with trastuzumab. These issues and others are discussed in this
      review.

PMID- 21847343
TI  - Gut microbiota: next frontier in understanding human health and development of
      biotherapeutics.
AB  - The gut microbiota is a remarkable asset for human health. As a key element in
      the development and prevention of specific diseases, its study has yielded a new
      field of promising biotherapeutics. This review provides comprehensive and
      updated knowledge of the human gut microbiota, its implications in health and
      disease, and the potentials and limitations of its modification by currently
      available biotherapeutics to treat, prevent and/or restore human health, and
      future directions. Homeostasis of the gut microbiota maintains various functions
      which are vital to the maintenance of human health. Disruption of the intestinal
      ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human
      diseases, including autoimmune and allergic diseases, colorectal cancer,
      metabolic diseases, and bacterial infections. Relevant underlying mechanisms by
      which specific intestinal bacteria populations might trigger the development of
      disease in susceptible hosts are being explored across the globe. Beneficial
      modulation of the gut microbiota using biotherapeutics, such as prebiotics,
      probiotics, and antibiotics, may favor health-promoting populations of bacteria
      and can be exploited in development of biotherapeutics. Other technologies, such
      as development of human gut models, bacterial screening, and delivery
      formulations eg, microencapsulated probiotics, may contribute significantly in
      the near future. Therefore, the human gut microbiota is a legitimate therapeutic
      target to treat and/or prevent various diseases. Development of a clear
      understanding of the technologies needed to exploit the gut microbiota is
      urgently required.

PMID- 21847345
TI  - Overactive bladder: the importance of tailoring treatment to the individual
      patient.
AB  - INTRODUCTION: Overactive bladder (OAB) is a prevalent and persistent condition
      that is often under-diagnosed and under-treated, and which frequently requires
      tailored treatment for successful management. METHODS: This consensus opinion
      based review summarizes the discussions of a group of experts in the field of OAB
      that were assembled to evaluate the importance of correct diagnosis and
      appropriate pharmacotherapy in patients with OAB. RESULTS: A thorough diagnostic
      process is crucial for allowing exclusion of underlying medical issues and
      differentiation from genitourinary conditions other than OAB. In addition,
      selecting the most appropriate pharmacotherapy needs to be carefully considered
      in the context of each patient with OAB. In general, patients with OAB tend to be
      older with various comorbidities and often receiving multiple concomitant
      medications. Treatment decisions should take into consideration the differing
      potential for antimuscarinic medications to alter cognitive and cardiovascular
      functions, both of which may be compromised in this patient population.
      CONCLUSION: Tailoring treatment to individual patients by comprehensive patient
      assessment may lead to more effective management of patients with OAB, especially
      those receiving polypharmacy for comorbidities.

PMID- 21847346
TI  - Age and gender as predictors of allied health quality stroke care.
AB  - BACKGROUND: Improvement in acute stroke care requires the identification of
      variables which may influence care quality. The nature and impact of demographic
      and stroke-related variables on care quality provided by allied health (AH)
      professionals is unknown. AIMS: Our research explores the association of age and
      gender on an index of acute stroke care quality provided by AH professionals.
      METHODS: A retrospective clinical audit of 300 acute stroke patients extracted
      data on AH care, patients' age and gender. AH care quality was determined by the
      summed compliance with 20 predetermined process indicators. Our analysis explored
      relationships between this index of quality, age, and gender. Age was considered
      in different ways (as a continuous variable, and in different categories). It was
      correlated with care quality, using gender-specific linear and logistic
      regression models. Gender was then considered as a confounder in an overall
      model. RESULTS: No significant association was found for any treatment of age and
      the index of AH care quality. There were no differences in gender-specific
      models, and gender did not significantly adjust the age association with care
      quality. CONCLUSION: Age and gender were not predictors of the quality of care
      provided to acute stroke patients by AH professionals.

PMID- 21847347
TI  - Demographic and stroke-related factors as predictors of quality of acute stroke
      care provided by allied health professionals.
AB  - BACKGROUND: We recently indicated that patient age on its own is not a
      determinant of quality of allied health care received after an acute stroke. It
      has not been tested whether other non-age variables influence care decisions made
      by allied health professionals. This paper explores demographic and stroke
      related variables that are putatively associated with the quality of care
      provided to acute stroke patients by allied health professionals. METHODS: Data
      were retrospectively audited from 300 acute stroke patient records regarding
      allied health care. Compliance with each of 20 indicators of allied health care
      quality was established. The influence of various demographic and stroke-related
      variables on each performance indicator was examined. We undertook a series of
      analyses using univariate logistic regression models to establish the influence
      of these variables on care quality. RESULTS: Patient age had a significant
      correlation with only one process indicator (early mobilization). Seven
      variables, including stroke severity and level of dependence, were associated
      with patient age. The majority of these age proxies had significant associations
      with process indicator compliance. Correlations between non-age variables, in
      particular stroke severity and comorbidity, suggest the potential for complex
      confounding relationships between non-age variables and quality of allied health
      care. CONCLUSION: Compliance with individual indicators of allied health care was
      significantly associated with variables other than patient age, and included
      stroke severity, previous independence, comorbidities, day of admission, stroke
      unit admission, and length of stay. The inter-relationships between these non-age
      variables suggest that their influence on quality of care is complex.

PMID- 21847348
TI  - A systematic review of the individual determinants of research evidence use in
      allied health.
AB  - BACKGROUND: The use of evidence-based practice (EBP) is often not reflected in
      allied health (AH) practitioners' day-to-day practice (the research-practice
      gap). Research suggests that considerable differences between and within AH
      disciplines exist, which require different approaches in order to influence
      practice behavior. It is therefore important to develop a better understanding of
      what influences individual AH practitioners' adoption of evidence into daily
      practice. OBJECTIVE: This systematic review aims to examine the individual
      characteristics of AH practitioners which determine their uptake of evidence into
      practice. METHODS: Studies which examined individual factors or variables that
      influence research evidence use by any AH practitioner were included in the
      review. The methodological quality of the included papers was assessed using the
      Quality Assessment and Validity Tool for Cross-sectional Studies. A narrative
      summary of the findings was presented. RESULTS: Six studies were included and the
      methodological quality scores indicated that two were weak and the remainder had
      moderate-weak quality. The review demonstrated that factors such as educational
      degree or academic qualification, involvement in research or EBP-related
      activities, and practitioners' perceptions, attitudes and beliefs about research
      and EBP are significant predictors of self-reported research evidence use in AH.
      The effect of other factors such as professional characteristics, clinical
      setting/work environment, information-seeking behavior and sociodemographic
      variables are less clear. Whether there is an interaction effect between evidence
      uptake factors has not been tested. CONCLUSION: Improving the research knowledge
      of clinicians and overcoming negative attitudes toward EBP have the potential to
      move AH practitioners towards regularly utilizing evidence in practice. Allied
      health practitioners may benefit from participation in regular educational
      opportunities such as case studies or journal clubs which can put them at the
      same level of thinking and awareness of research evidence. Future research should
      aim to review organizational and contextual factors and explore their interaction
      with individual determinants of research evidence use.

PMID- 21847349
TI  - Self-care and anticipated transition into retirement and later life in a Nordic
      welfare context.
AB  - Few studies have appeared in the health care literature on the meaning of
      transition into retirement and later life. However, this predictable-involuntary
      transition may influence personal health and well-being, and studying it from a
      self-care perspective could be useful. The aim of this study was to illuminate
      aspects of self-care in a group of middle-aged individuals in relation to their
      anticipated transition into retirement in the Nordic welfare context. A total of
      13 individuals, aged 55 to 65 years, were randomly chosen from the total number
      of inhabitants in three municipalities in mid-west Sweden. Conversational
      interviews took place, during which the informants shared important events in
      their lives that had occurred from early childhood until the present time,
      together with thoughts about their anticipated future developmental transition
      into later life. The interviews were tape recorded and transcribed verbatim.
      After content analyses and interpretation, a comprehensive picture of the
      phenomenon was revealed. The results showed that there were opportunities,
      expectations, wishes, concerns, and worries related to the transition into
      retirement and old age among informants from both rural and urban municipalities.
      Self-care, in connection with this, depended on motivating and demotivating
      factors. Autonomy and mature dependence seemed to be positive driving forces for
      reaching a successful transition into later life. Supporting autonomy should be a
      way of facilitating the transition into retirement and later life.

PMID- 21847350
TI  - Differences in symptoms, functioning, and quality of life between women on long
      term sick-leave with musculoskeletal pain with and without concomitant
      depression.
AB  - OBJECTIVE: The aim was to describe the differences in symptoms, functioning and
      quality of life between women on long-term sick-leave due to protracted
      musculoskeletal pain with and without concomitant depression. DESIGN: Descriptive
      and comparisons with/without comorbid depression. METHODS: 332 female patients
      were examined by three specialist physicians in psychiatry, orthopedic surgery,
      and rehabilitation medicine and assigned to four groups according to the ICD-10
      diagnoses: low back/joint disorders (LBJ, n = 150), myalgia (M, n = 43),
      fibromyalgia (FM, n = 87), or depression without somatic pain diagnosis (DE, n =
      52). RESULTS: Patients with somatic pain conditions LBJ, M, or FM showed more
      activity-related difficulties if concomitant depression was present during the
      activities 'focusing attention', 'making decisions', and 'undertaking a single
      task'; and in the domains 'energy level', 'memory functions', 'emotional
      functions', and 'optimism/pessimism'. Patients with FM and concomitant depression
      perceived higher pain intensity than patients in group DE. No statistically
      significant differences in physically related activities were noted between each
      of the somatic pain conditions with and without coexisting depression. FM
      patients with coexisting depression reported fewer painful sites on their pain
      drawings compared with FM-patients without depression. Patients with LBJ or FM
      and concomitant depression reported lower quality of life in the dimensions
      vitality, social functioning, emotional role, and mental health. Comorbid
      depression affected disability and restricted working capacity by reducing mental
      activity and functioning but not by affecting physical activity problems.
      CONCLUSION: Women on long-term sick-leave, who have concomitant depression with
      LBJ or FM, also have more difficulties in focusing attention, making decisions,
      and carrying out tasks, and with memory functions and optimism/pessimism, as well
      as reduced quality of life in the dimensions of vitality, social functioning,
      emotional role, and mental health, than female patients without comorbid
      depression. As a consequence we suggest further efforts to integrate somatic and
      psychiatric interventions in the same rehabilitation program.

PMID- 21847351
TI  - Health and Gross National Happiness: review of current status in Bhutan.
AB  - Worldwide, contemporary measures of the success of health development programs
      have been mostly in terms of the reduction of mortality and morbidity as well as
      increasing longevity. While these goals have yielded much-needed health
      improvements, the subjective outcomes of these improvements, as experienced by
      individuals and the communities, have not been considered. Bhutan, under the
      overarching policy of Gross National Happiness, has provided due consideration to
      these subjective indicators. Here, we report on the current status of health and
      happiness in Bhutan as revealed by conventional objective indicators and
      subjective Gross National Happiness indicators. The current literature on health
      in Bhutan in relation to the Gross National Happiness Survey conducted by the
      Centre of Bhutan Studies has been reviewed. Bhutan has made great strides within
      a short period of modernization, as shown by both objective and subjective
      indicators. Tremendous challenges lie ahead to achieve the ultimate goal of
      health and happiness, and how Bhutan articulates its path to modernization may be
      a lesson for the rest of the world.

PMID- 21847352
TI  - Helping patients attain and maintain asthma control: reviewing the role of the
      nurse practitioner.
AB  - Nurse practitioners (NPs) have a unique opportunity as frontline caregivers and
      patient educators to recognize, assess, and effectively treat the widespread
      problem of uncontrolled asthma. This review provides a perspective on the role of
      the NP in implementing the revised National Asthma Education and Prevention
      Program (NAEPP) Guidelines put forth by the National Heart, Lung, and Blood
      Institute, thereby helping patients achieve and maintain asthma control. A
      literature search of PubMed was performed using the terms asthma, nurse
      practitioner, asthma control, burden, impact, morbidity, mortality, productivity,
      quality of life, uncontrolled asthma, NAEPP guidelines, assessment,
      pharmacotherapy, safety. Despite the increased morbidity and mortality and
      impaired quality of life attributable to uncontrolled asthma, the 2007 NAEPP
      asthma guidelines are greatly underused. NPs have an opportunity to identify
      patients at risk and provide enhanced care and education for asthma control.
      Often, NPs can prescribe medication for and manage these patients, but it is
      necessary to be able to discern which patients require referral to a specialist.

PMID- 21847354
TI  - Comparison of the impact of radiotherapy and radiochemotherapy on the quality of
      life of 1-year survivors with cervical cancer.
AB  - Improvement of screening programs and new treatment strategies against cervical
      cancer (CC) have increased survival rates of patients in the last decades. As
      more women survive this type of cancer, their quality of life (QOL) has become a
      field of great scientific and social importance. Different types of therapy have
      varying results on the QOL of patients. In this study, we compared the impact of
      radiotherapy (RAD) and radiochemotherapy (RAD/CHEM) on CC patients' QOL. Our
      sample included 105 women who suffered from CC stages IA-IIIA. They were treated
      either with RAD or RAD/CHEM, and filled in the questionnaires 1 year after
      treatment completion. We used 4 questionnaires, EORTC QLQ C-30, EORTC QLQ-C24,
      Questionnaire of Post-traumatic Psychological Disorder, and Greek Symptom Control
      Questionnaire by M.D. Anderson, in order to assess their QOL. Except for
      differences in descriptive characteristics of the patients' (age, number of
      children, contraceptives) and early toxicity in some organs, no statistically
      significant difference was observed in the main (physical, sexual, emotional)
      aspects of life between the 2 groups of treated patients. Treatment type had no
      effect on total QOL. In conclusion, the addition of CHEM to RAD in the treatment
      plan of CC patients had no significant impact on their QOL.

PMID- 21847353
TI  - Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy,
      safety, convenience, and comfort.
AB  - Two different 6-month GnRH agonist depot formulations approved for palliative
      treatment of advanced and metastatic prostate cancer in the United States -
      leuprolide acetate 45 mg and triptorelin pamoate 22.5 mg - provide patients with
      efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH
      agonist depots. However, the 6-month formulations can increase patient
      convenience, comfort, and compliance by reducing the number of physician visits
      and injections required. At the conclusion of their pivotal trials, the 6-month
      formulations demonstrated efficacy rates in achieving chemical castration (serum
      testosterone <=50 ng/dL) that ranged between 93% and 99%. As with existing GnRH
      agonist depot formulations, hot flashes represented the most common adverse event
      reported in trials of 6-month leuprolide acetate or triptorelin. As such, these
      products may prove useful not only for their labeled indication, but also as
      adjuncts to other treatments such as radical prostatectomy, radiotherapy, and
      chemotherapy. We recommend further research, including head-to-head trials
      between the 6-month GnRH depots, to refine our understanding of these products.

PMID- 21847355
TI  - Factors influencing distant recurrence of hepatocellular carcinoma following
      combined radiofrequency ablation and transarterial chemoembolization therapy in
      patients with hepatitis C.
AB  - BACKGROUND: The purpose of this study was to clarify important risk factors for
      distant recurrence of hepatocellular carcinoma in patients positive for hepatitis
      C and without local recurrence. METHODS: A total of 212 patients (145 males and
      67 females) underwent radiofrequency ablation and transcatheter arterial
      embolization or transcatheter arterial chemoembolization at initial development
      of hepatocellular carcinoma. All patients were positive for hepatitis C. Child
      Pugh classification was A in 115 and B in 97. The indication for radiofrequency
      ablation was the presence of up to three tumors <= 3 cm. The distant recurrence
      rate was analyzed using the Kaplan-Meier method and tested by Wilcoxon's method.
      RESULTS: Cumulative distant recurrence rates at years 1, 3, and 5 were 19%, 62%,
      and 79%, respectively. On univariate analysis, a >= 3 cm tumor, >= 50 ng/mL alpha
      fetoprotein level, and < 3.6 g/dL serum albumin level were significant risk
      factors for distant recurrence, but only a serum albumin level < 3.6 g/dL (P =
      0.004) was identified as significant on multivariate analysis. In the group with
      a pretreatment albumin level >= 3.6 g/dL, the distant recurrence rate was
      compared between patients in whom the albumin level rose, remained unchanged, or
      decreased by < 0.3 g/dL, and those in whom the level decreased by >= 0.3 g/dL.
      The rate was significantly higher in the latter, with a one-year recurrence rate
      of 7% versus 15% (P = 0.04). CONCLUSION: Distant recurrence was significantly
      decreased in patients with a high serum albumin level. Distant recurrence was
      more likely to occur in patients with a decreased albumin level, although the
      pretreatment level was high. Thus, strict follow-up after treatment for
      hepatocellular carcinoma is necessary in patients with low serum albumin levels.

PMID- 21847356
TI  - A(2A) adenosine receptor-mediated increase in coronary flow in hyperlipidemic
      APOE-knockout mice.
AB  - Adenosine-induced coronary vasodilation is predominantly A(2A) adenosine receptor
      (AR)-mediated, whereas A(1) AR is known to negatively modulate the coronary flow
      (CF). However, the coronary responses to adenosine in hyperlipidemia and
      atherosclerosis are not well understood. Using hyperlipidemic/atherosclerotic
      apolipoprotein E (APOE)-knockout mice, CF responses to nonspecific adenosine
      agonist (5'-N-ethylcarboxamide adenosine, NECA) and specific adenosine agonists
      (2-chloro-N6-cyclopentyl-adenosine [CCPA, A(1) AR-specific] and CGS-21680, A(2A)
      AR-specific) were assessed using isolated Langendorff hearts. Western blot
      analysis was performed in the aorta from APOE and their wild-type (WT) control
      (C57BL/6J). Baseline CF (expressed as mL/min/g heart weight) was not different
      among WT (13.23 +/- 3.58), APOE (13.22 +/- 2.78), and APOE on high-fat diet (HFD)
      for 12 weeks (APOE-HFD, 12.37 +/- 4.76). Concentration response curves induced by
      CGS-21680 were significantly shifted to the left in APOE and APOE-HFD when
      compared with WT. CCPA induced an increase in CF only at 10(-6) M in all groups
      and the effect was reversed by the addition of a selective A(2A) AR antagonist,
      SCH-58261 (10(-6) M), and a significant decrease in CF from baseline was
      observed. Western blot analysis showed a significant upregulation of A(2A) AR in
      the aorta from APOE and APOE-HFD. This study provides the first evidence that CF
      responses to A(2A) AR stimulation were upregulated in
      hyperlipidemic/atherosclerotic animals. The speculation is that the use of A(2A)
      AR-specific agonist for myocardial perfusion imaging (such as regadenoson) could
      overestimate the coronary reserve in coronary artery disease patients.

PMID- 21847357
TI  - Early acquisition of sign language What neuroimaging data tell us.
AB  - Early acquisition of a natural language, signed or spoken, has been shown to
      fundamentally impact both one's ability to use the first language, and the
      ability to learn subsequent languages later in life (Mayberry 2007, 2009). This
      review summarizes a number of recent neuroimaging studies in order to detail the
      neural bases of sign language acquisition. The logic of this review is to present
      research reports that contribute to the bigger picture showing that people who
      acquire a natural language, spoken or signed, in the normal way possess
      specialized linguistic abilities and brain functions that are missing or
      deficient in people whose exposure to natural language is delayed or absent.
      Comparing the function of each brain region with regards to the processing of
      spoken and sign languages, we attempt to clarify the role each region plays in
      language processing in general, and to outline the challenges and remaining
      questions in understanding language processing in the brain.

PMID- 21847358
TI  - Interleukin 1alpha sustains the expression of inflammatory factors in human
      pancreatic cancer microenvironment by targeting cancer-associated fibroblasts.
AB  - The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic,
      with an extensive interaction between the stroma and tumor cells. The aim of this
      study was to delineate the cross talk between PDAC and cancer-associated
      fibroblasts (CAFs), with a focus on the mechanism creating the chronic
      inflammatory tumor milieu. We assessed the effects of the cross talk between PDAC
      and CAF cell lines on the creation and sustenance of the inflammatory tumor
      microenvironment in pancreatic cancer. The coculture of PDAC and CAF cell lines
      enhanced the levels of inflammatory factors including IL-1alpha, IL-6, CXCL8,
      VEGF-A, CCL20, and COX-2. CAFs were superior to tumor cells regarding the
      production of most inflammatory factors, and tumor cell-associated IL-1alpha was
      established as the initiator of the enhanced production of inflammatory factors
      through the binding of IL-1alpha to IL-1 receptor 1 (IL-1R1) expressed
      predominantly by CAFs. Furthermore, we found a correlation between IL-1alpha and
      CXCL8 expression levels in PDAC tissues and correlation between IL-1alpha
      expression and the clinical outcome of the patients. This confirmed an important
      role for the IL-1 signaling cascade in the creation and sustenance of a tumor
      favorable microenvironment. Neutralization of the IL-1alpha signaling efficiently
      diminished the cross talk-induced production of inflammatory factors. These data
      suggest that the cross talk between PDAC cells and the main stroma cell type,
      i.e. CAFs, is one essential factor in the formation of the inflammatory tumor
      environment, and we propose that neutralization of the IL-1alpha signaling might
      be a potential therapy for this cancer.

PMID- 21847359
TI  - Enhanced expression of EHMT2 is involved in the proliferation of cancer cells
      through negative regulation of SIAH1.
AB  - EHMT2 is a histone lysine methyltransferase localized in euchromatin regions and
      acting as a corepressor for specific transcription factors. Although the role of
      EHMT2 in transcriptional regulation has been well documented, the pathologic
      consequences of its dysfunction in human disease have not been well understood.
      Here, we describe important roles of EHMT2 in human carcinogenesis. Expression
      levels of EHMT2 are significantly elevated in human bladder carcinomas compared
      with nonneoplastic bladder tissues (P < .0001) in real-time polymerase chain
      reaction analysis. Complementary DNA microarray analysis also revealed its
      overexpression in various types of cancer. The reduction of EHMT2 expression by
      small interfering RNAs resulted in the suppression of the growth of cancer cells
      and possibly caused apoptotic cell death in cancer cells. Importantly, we show
      that EHMT2 can suppress transcription of the SIAH1 gene by binding to its
      promoter region (-293 to +51) and by methylating lysine 9 of histone H3.
      Furthermore, an EHMT2-specific inhibitor, BIX-01294, significantly suppressed the
      growth of cancer cells. Our results suggest that dysregulation of EHMT2 plays an
      important role in the growth regulation of cancer cells, and further functional
      studies may affirm the importance of EHMT2 as a promising therapeutic target for
      various types of cancer.

PMID- 21847360
TI  - Detection of colorectal adenomas using a bioactivatable probe specific for matrix
      metalloproteinase activity.
AB  - A significant proportion of colorectal adenomas, in particular those that lack an
      elevated growth component, continue to escape detection during endoscopic
      surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a
      large family of zinc endopeptidases, in adenomas serves as a biomarker of early
      tumorigenesis. The goal of this study was to assess the feasibility of using a
      newly developed near-infrared bioactivatable probe (MMPSense 680) that reports
      the activity of a broad array of MMP isoforms to detect early colorectal
      adenomas. Adenomatous polyposis coli (Apc)(+/Min-FCCC) mice that spontaneously
      develop multiple colorectal adenomas were injected with MMPSense 680, and the
      colons were imaged in an IVIS Spectrum system ex vivo. Image analyses were
      correlated with histopathologic findings for all regions of interest (ROIs). The
      biochemical basis of fluorescent signal was investigated by immunohistochemical
      staining of MMP-7 and -9. A strong correlation (Kendall = 0.80) was observed
      between a positive signal and the presence of pathologically confirmed colonic
      adenomas; 92.9% of the 350 ROIs evaluated were classified correctly. The
      correlation between two independent observers was 0.87. MMP-7 expression was
      localized to epithelial cells of adenomas and microadenomas, whereas staining of
      MMP-9 was found in infiltrating polymorphonuclear leukocytes within the adenomas.
      MMPSense 680 identifies colorectal adenomas, both polypoid and nonpolypoid, in
      Apc(+/Min-FCCC) mice with high specificity. Use of this fluorescent probe in
      combination with colonoscopy could aid in preventing colorectal neoplasias by
      providing new opportunities for early detection and therapeutic intervention.

PMID- 21847361
TI  - Persistent inflammation leads to proliferative neoplasia and loss of smooth
      muscle cells in a prostate tumor model.
AB  - In prostate cancers, epidemiological data suggest a link between prostate
      inflammation and subsequent cancer development, but proof for this concept in a
      tumor model is lacking. A constitutively active version of IkappaB kinase 2
      (IKK2), which is activated by many inflammatory stimuli, was expressed
      specifically in the prostate epithelium. Constitutive activation of the
      IKK2/nuclear factor kappaB axis was insufficient for prostate transformation.
      However, in combination with heterozygous loss of phosphatase and tensin homolog,
      IKK2 activation led to an increase in tumor size, formation of cribriform
      structures, and increase in fiber in the fibroblastic stroma. This phenotype was
      coupled with persistent inflammation evoked by chemokine expression in the
      epithelium and stroma. The hyperplastic and dysplastic epithelia correlated with
      changes evoked by decreased androgen receptor activation. Conversely,
      inflammation correlated with stromal changes highlighted by loss of smooth muscle
      cells around prostate ducts. Despite the loss of the smooth muscle barrier,
      tumors were rarely invasive in a C57BL/6 background. Data mining revealed that
      smooth muscle markers are also downregulated in human prostate cancers, and loss
      of these markers in primary tumors is associated with subsequent metastasis. In
      conclusion, our data show that loss of smooth muscle and invasiveness of the
      tumor are not coupled in our model, with inflammation leading to increased tumor
      size and a dedifferentiated stroma.

PMID- 21847362
TI  - Identification of oncogenic point mutations and hyperphosphorylation of
      anaplastic lymphoma kinase in lung cancer.
AB  - The oncogenic property of anaplastic lymphoma kinase (ALK) plays an essential
      role in the pathogenesis of various cancers and serves as an important
      therapeutic target. In this study, we identified frequent intragenic loss of
      heterozygosity and six novel driver mutations within ALK in lung adenocarcinomas.
      Overexpression of H694R or E1384K mutant ALK leads to hyperphosphorylation of
      ALK, and activation of its downstream mediators STAT3, AKT, and ERK resulted in
      enhanced cell proliferation, colony formation, cell migration, and tumor growth
      in xenograft models. Furthermore, the activated phospho-Y1604 ALK was
      increasingly detected in 13 human lung cancer cell lines and 263 lung cancer
      specimens regardless of tumor stages and types. Treatment of two different ALK
      inhibitors, WHI-P154 and NVP-TAE684, resulted in the down-regulation of aberrant
      ALK signaling, shrinkage of tumor, and suppression of metastasis and
      significantly improved survival of ALK mutant-bearing mice. Together, we
      identified that novel ALK point mutations possessed tumorigenic effects mainly
      through hyperphosphorylation of Y1604 and activation of downstream oncogenic
      signaling. The upregulated phospho-Y1604 ALK could serve as a diagnostic
      biomarker for lung cancer. Furthermore, targeting oncogenic mutant ALKs with
      inhibitors could be a promising strategy to improve the therapeutic efficacy of
      fatal lung cancers.

PMID- 21847363
TI  - Mesenchymal stem cells display tumor-specific tropism in an RCAS/Ntv-a glioma
      model.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to
      gliomas and deliver therapeutic agents. However, the clinical translation of MSCs
      remains poorly defined because previous studies relied on glioma models with
      uncertain relevance to human disease, typically xenograft models in
      immunocompromised mice. To address this shortcoming, we used the RCAS/Ntv-a
      system, in which endogenous gliomas that recapitulate the tumor and stromal
      features of human gliomas develop in immunocompetent mice. MSCs were harvested
      from bone marrow of Ntv-a mice and injected into the carotid artery of Ntv-a mice
      previously inoculated with RCAS-PDGF-B and RCAS-IGFBP2 to induce malignant
      gliomas (n = 9). MSCs were labeled with luciferase for in vivo bioluminescence
      imaging (BLI). After intra-arterial injection, BLI revealed MSCs in the right
      frontal lobe in seven of nine mice. At necropsy, gliomas were detected within the
      right frontal lobe in all these mice, correlating with the location of the MSCs.
      In the two mice without MSCs based on BLI, no tumor was found, indicating that
      MSC localization was tumor specific. In another cohort of mice (n = 9), MSCs were
      labeled with SP-DiI, a fluorescent vital dye. After intra-arterial injection,
      fluorescence microscopy revealed SP-DiI-labeled MSCs throughout tumors 1 to 7
      days after injection but not in nontumoral areas of the brain. MSCs injected
      intravenously did not localize to tumors (n = 12). We conclude that syngeneic
      MSCs are capable of homing to endogenous gliomas in immunocompetent mice. These
      findings support the use of MSCs as tumor-specific delivery vehicles for treating
      gliomas.

PMID- 21847365
TI  - Suppression of glypican 3 inhibits growth of hepatocellular carcinoma cells
      through up-regulation of TGF-beta2.
AB  - Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic
      target in hepatocellular carcinoma (HCC). To evaluate the efficacy of targeting
      GPC3 at the translational level, we used RNA interference to examine the biologic
      and molecular effects of GPC3 suppression in HCC cells in vitro and in vivo.
      Transfection of Huh7 and HepG2 cells with GPC3-specific small interfering RNA
      (siRNA) inhibited cell proliferation (P < .001) together with cell cycle arrest
      at the G(1) phase, down-regulation of antiapoptotic protein (Bcl-2, Bcl-xL, and
      Mcl-1), and replicative senescence. Gene expression analysis revealed that GPC3
      suppression significantly correlated with transforming growth factor beta
      receptor (TGFBR) pathway (P = 4.57e-5) and upregulated TGF-beta2 at both RNA and
      protein levels. The effects of GPC3 suppression by siRNA can be recapitulated by
      addition of human recombinant TGF-beta2 to HCC cells in culture, suggesting the
      possible involvement of TGF-beta2 in growth inhibition of HCC cells.
      Cotransfection of siRNA-GPC3 with siRNA-TGF-beta2 partially attenuated the
      effects of GPC3 suppression on cell proliferation, cell cycle progression,
      apoptosis, and replicative senescence, confirming the involvement of TGF-beta2 in
      siRNA-GPC3-mediated growth suppression. In vivo, GPC3 suppression significantly
      inhibited the growth of orthotopic xenografts of Huh7 and HepG2 cells (P < .05),
      accompanied by increased TGF-beta2 expression, reduced cell proliferation
      (observed by proliferating cell nuclear antigen staining), and enhanced apoptosis
      (by TUNEL staining). In conclusion, molecular targeting of GPC3 at the
      translational level offers an effective option for the clinical management of
      GPC3-positive HCC patients.

PMID- 21847364
TI  - HDAC6 deacetylates Ku70 and regulates Ku70-Bax binding in neuroblastoma.
AB  - Ku70 was first characterized as a nuclear factor that binds DNA double-strand
      breaks in nonhomolog end-joining DNA repair. However, recent studies have shown
      that Ku70 is also found in the cytoplasm and binds Bax, preventing Bax-induced
      cell death. We have shown that, in neuroblastoma cells, the binding between Ku70
      and Bax depends on the acetylation status of Ku70, such that, when Ku70 is
      acetylated, Bax is released from Ku70, triggering cell death. Thus, to survive,
      in neuroblastoma cells, cytoplasmic Ku70 acetylation status is carefully
      regulated such that Ku70 is maintained in a deacetylated state, keeping Bax
      complexed with Ku70. We have shown that overexpression of CREB-binding protein
      (CBP), a known acetyltransferase that acetylates Ku70, releases Bax from Ku70,
      triggering apoptosis. Although we have shown that blocking deacetylase activity
      using non-type-specific inhibitors also triggers Ku70 acetylation and Bax
      dependent cell death, the targets of these deacetylase inhibitors in
      neuroblastoma cells remain unknown. Here, we demonstrate that, in neuroblastoma
      cells, histone deacetylase 6 (HDAC6) binds Ku70 and Bax in the cytoplasm and that
      knocking down HDAC6 or using an HDAC6-specific inhibitor triggers Bax-dependent
      cell death. Our results show that HDAC6 regulates the interaction between Ku70
      and Bax in neuroblastoma cells and may be a therapeutic target in this pediatric
      solid tumor.

PMID- 21847366
TI  - B lymphocytes promote lymphogenous metastasis of lymphoma and melanoma.
AB  - The prognosis of patients with many types of cancers correlates with the degree
      of metastasis to regional lymph nodes (LNs) and vital organs. However, the
      mechanisms and route of cancer cell metastasis are still unclear. Previous
      studies determined that B-cell accumulation in tumor-draining LNs (TDLNs) induces
      lymphatic sinus growth (lymphangiogenesis) and increases lymph flow, which could
      actively promote tumor dissemination through the lymphatic system. Using young Eu
      c-Myc mice that feature LN B-cell expansion as hosts for tumor transplants, we
      show that subcutaneously implanted lymphomas or melanomas preferentially spread
      to TDLNs over non-TDLNs, thus demonstrating that these tumors initially
      metastasize through lymphatic rather than through hematogenous routes. In
      addition, the rate and amount of tumor dissemination is greater in Eu-c-Myc mice
      versus wild-type hosts, which correlates with LN B-cell accumulation and
      lymphangiogenesis in Eu-c-Myc hosts. The increased lymphatic dissemination in Eu
      c-Myc hosts is further associated with rapid hematogenous tumor spread of
      subcutaneously implanted lymphomas, suggesting that TDLN metastasis secondarily
      drives lymphoma spread to distant organs. In contrast, after intravenous tumor
      cell injection, spleen metastasis of lymphoma cells or lung metastasis of
      melanoma cells is similar in Eu-c-Myc and wild-type hosts. These studies
      demonstrate that the effect of Eu-c-Myc hosts to promote metastasis is limited to
      the lymphatic route of dissemination. TDLN B-cell accumulation, in association
      with lymphangiogenesis and increased lymph flow, thus significantly contributes
      to dissemination of lymphomas and solid tumors, providing new targets for
      therapeutic intervention to block metastasis.

PMID- 21847367
TI  - Type III TGF-beta receptor enhances colon cancer cell migration and anchorage
      independent growth.
AB  - The type III TGF-beta receptor (TbetaRIII or betagylcan) is a TGF-beta
      superfamily coreceptor with emerging roles in regulating TGF-beta superfamily
      signaling and cancer progression. Alterations in TGF-beta superfamily signaling
      are common in colon cancer; however, the role of TbetaRIII has not been examined.
      Although TbetaRIII expression is frequently lost at the message and protein level
      in human cancers and suppresses cancer progression in these contexts, here we
      demonstrate that, in colon cancer, TbetaRIII messenger RNA expression is not
      significantly altered and TbetaRIII expression is more frequently increased at
      the protein level, suggesting a distinct role for TbetaRIII in colon cancer.
      Increasing TbetaRIII expression in colon cancer model systems enhanced ligand
      mediated phosphorylation of p38 and the Smad proteins, while switching TGF-beta
      and BMP-2 from inhibitors to stimulators of colon cancer cell proliferation,
      inhibiting ligand-induced p21 and p27 expression. In addition, increasing
      TbetaRIII expression increased ligand-stimulated anchorage-independent growth, a
      resistance to ligand- and chemotherapy-induced apoptosis, cell migration and
      modestly increased tumorigenicity in vivo. In a reciprocal manner, silencing
      endogenous TbetaRIII expression decreased colon cancer cell migration. These data
      support a model whereby TbetaRIII mediates TGF-beta superfamily ligand-induced
      colon cancer progression and support a context-dependent role for TbetaRIII in
      regulating cancer progression.

PMID- 21847369
TI  - Frequency-Dependent Cannabinoid Receptor-Independent Modulation of Glycine
      Receptors by Endocannabinoid 2-AG.
AB  - Endocannabinoids are known as retrograde messengers, being released from the
      postsynaptic neuron and acting on specific presynaptic G-protein-coupled
      cannabinoid (CB) receptors to decrease neurotransmitter release. Also, at
      physiologically relevant concentrations cannabinoids can directly modulate the
      function of voltage-gated and receptor-operated ion channels. Using patch-clamp
      recording we analyzed the consequences of the direct action of an
      endocannabinoid, 2-arachidonoylglycerol (2-AG), on the functional properties of
      glycine receptor channels (GlyRs) and ionic currents in glycinergic synapses. At
      physiologically relevant concentrations (0.1-1 MUM), 2-AG directly affected the
      functions of recombinant homomeric alpha1H GlyR: it inhibited peak amplitude and
      dramatically enhanced desensitization. The action of 2-AG on GlyR-mediated
      currents developed rapidly, within ~300 ms. Addition of 1 MUM 2-AG strongly
      facilitated the depression of glycine-induced currents during repetitive (4-10
      Hz) application of short (2 ms duration) pulses of glycine to outside-out
      patches. In brainstem slices from CB1 receptor knockout mice, 2-AG significantly
      decreased the extent of facilitation of synaptic currents in hypoglossal
      motoneurons during repetitive (10-20 Hz) stimulation. These observations suggest
      that endocannabinoids can modulate postsynaptic metaplasticity of glycinergic
      synaptic currents in a CB1 receptor-independent manner.

PMID- 21847368
TI  - The Roles of Glutathione Peroxidases during Embryo Development.
AB  - Embryo development relies on the complex interplay of the basic cellular
      processes including proliferation, differentiation, and apoptotic cell death.
      Precise regulation of these events is the basis for the establishment of
      embryonic structures and the organ development. Beginning with fertilization of
      the oocyte until delivery the developing embryo encounters changing environmental
      conditions such as varying levels of oxygen, which can give rise to reactive
      oxygen species (ROS). These challenges are met by the embryo with metabolic
      adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious
      by modifying biological molecules including lipids, proteins, and nucleic acids
      and may induce abnormal development or even embryonic lethality. On the other
      hand ROS are vital players of various signaling cascades that affect the balance
      between cell growth, differentiation, and death. An imbalance or dysregulation of
      these biological processes may generate cells with abnormal growth and is
      therefore potentially teratogenic and tumorigenic. Thus, a precise balance
      between processes generating ROS and those decomposing ROS is critical for normal
      embryo development. One tier of the cellular protective system against ROS
      constitutes the family of selenium-dependent glutathione peroxidases (GPx). These
      enzymes reduce hydroperoxides to the corresponding alcohols at the expense of
      reduced glutathione. Of special interest within this protein family is the
      moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger
      of lipophilic hydroperoxides on one hand, but on the other hand can be
      transformed into an enzymatically inactive cellular structural component. GPx4
      deficiency - in contrast to all other GPx family members - leads to abnormal
      embryo development and finally produces a lethal phenotype in mice. This review
      is aimed at summarizing the current knowledge on GPx isoforms during embryo
      development and tumor development with an emphasis on GPx4.

PMID- 21847370
TI  - GABA(A) Receptor beta3 Subunit Expression Regulates Tonic Current in Developing
      Striatopallidal Medium Spiny Neurons.
AB  - The striatum is a key structure for movement control, but the mechanisms that
      dictate the output of distinct subpopulations of medium spiny projection neurons
      (MSNs), striatonigral projecting and dopamine D1 receptor- (D1+) or
      striatopallidal projecting and dopamine D2 receptor- (D2+) expressing neurons,
      remains poorly understood. GABA-mediated tonic inhibition largely controls
      neuronal excitability and action potential firing rates, and we previously
      suggested with pharmacological analysis that the GABA(A) receptor beta3 subunit
      plays a large role in the basal tonic current seen in D2+ MSNs from young mice
      (Ade et al., 2008; Janssen et al., 2009). In this study, we demonstrated the
      essential role of the beta3 GABA(A) receptor subunit in mediating MSN tonic
      currents using conditional beta3 subunit knock-out (beta3f/f(Drd2)) mice. Cre-lox
      genetics were used to generate mice where Cre recombinase was expressed under the
      D2 receptor (Drd2) promoter. We show that while the wild-type MSN tonic current
      pattern demonstrates a high degree of variability, tonic current patterns from
      beta3f/f(Drd2) mice are narrow, suggesting that the beta3 subunit is essential to
      striatal MSN GABA-mediated tonic current. Our data also suggest that a distinct
      population of synaptic receptors upregulate due to beta3 subunit removal.
      Further, deletion of this subunit significantly decreases the D2+ MSN
      excitability. These results offer insight for target mechanisms in Parkinson's
      disease, where symptoms arise due to the imbalance in striatal D1+ and D2+ MSN
      excitability and output.

PMID- 21847371
TI  - Phenobarbital but Not Diazepam Reduces AMPA/kainate Receptor Mediated Currents
      and Exerts Opposite Actions on Initial Seizures in the Neonatal Rat Hippocampus.
AB  - Diazepam (DZP) and phenobarbital (PB) are extensively used as first and second
      line drugs to treat acute seizures in neonates and their actions are thought to
      be mediated by increasing the actions of GABAergic signals. Yet, their efficacy
      is variable with occasional failure or even aggravation of recurrent seizures
      questioning whether other mechanisms are not involved in their actions. We have
      now compared the effects of DZP and PB on ictal-like events (ILEs) in an in vitro
      model of mirror focus (MF). Using the three-compartment chamber with the two
      immature hippocampi and their commissural fibers placed in three different
      compartments, kainate was applied to one hippocampus and PB or DZP to the
      contralateral one, either after one ILE, or after many recurrent ILEs that
      produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated
      propagating ILEs from the start, and did not prevent the formation of MF. PB
      reduced and DZP increased the network driven giant depolarizing potentials
      suggesting that PB may exert additional actions that are not mediated by GABA
      signaling. In keeping with this, PB but not DZP reduced field potentials recorded
      in the presence of GABA and NMDA receptor antagonists. These effects are mediated
      by a direct action on AMPA/kainate receptors since PB: (i) reduced AMPA/kainate
      receptor mediated currents induced by focal applications of glutamate; (ii)
      reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated
      miniature excitatory postsynaptic currents (EPSCs); (iii) augmented the number of
      AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These
      effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly
      by reducing AMPA/kainate receptors mediated EPSCs in addition to the pro-GABA
      effects. We suggest that PB may have advantage over DZP in the treatment of
      initial neonatal seizures since the additional reduction of glutamate receptors
      mediated signals may reduce the severity of neonatal seizures.

PMID- 21847372
TI  - Wiring of divergent networks in the central auditory system.
AB  - Divergent axonal projections are found throughout the central auditory system.
      Here, we evaluate these branched projections in terms of their types,
      distribution, and putative physiological roles. In general, three patterns of
      axon collateralization are found: intricate local branching, long-distance
      collaterals, and branched axons (BAs) involved in feedback-control loops. Local
      collaterals in the auditory cortex may be involved in local processing and
      modulation of neuronal firing, while long-range collaterals are optimized for
      wide-dissemination of information. Rarely do axons branch to both ascending and
      descending targets. Branched projections to two or more widely separated nuclei
      or areas are numerically sparse but widespread. Finally, branching to
      contralateral targets is evident at multiple levels of the auditory pathway and
      may enhance binaural computations for sound localization. These patterns of
      axonal branching are comparable to those observed in other modalities. We
      conclude that the operations served by BAs are area- and nucleus-specific and may
      complement the divergent unbranched projections of local neuronal populations.

PMID- 21847374
TI  - Neural underpinnings of distortions in the experience of time across senses.
AB  - Auditory signals (A) are perceived as lasting longer than visual signals (V) of
      the same physical duration when they are compared together. Despite considerable
      debate about how this illusion arises psychologically, the neural underpinnings
      have not been studied. We used functional magnetic resonance imaging (fMRI) to
      investigate the neural bases of audiovisual temporal distortions and more
      generally, intersensory timing. Adults underwent fMRI while judging the relative
      duration of successively presented standard interval-comparison interval (CI)
      pairs, which were unimodal (A-A, V-V) or crossmodal (V-A, A-V). Mechanisms of
      time dilation and compression were identified by comparing the two crossmodal
      pairs. Mechanisms of intersensory timing were identified by comparing the
      unimodal and crossmodal conditions. The behavioral results showed that auditory
      CIs were perceived as lasting longer than visual CIs. There were three novel fMRI
      results. First, time dilation and compression were distinguished by differential
      activation of higher-sensory areas (superior temporal, posterior insula, middle
      occipital), which typically showed stronger effective connectivity when time was
      dilated (V-A). Second, when time was compressed (A-V) activation was greater in
      frontal cognitive-control centers, which guide decision making. These areas did
      not exhibit effective connectivity. Third, intrasensory timing was distinguished
      from intersensory timing partly by decreased striatal and increased superior
      parietal activation. These regions showed stronger connectivity with visual,
      memory, and cognitive-control centers during intersensory timing. Altogether, the
      results indicate that time dilation and compression arise from the connectivity
      strength of higher-sensory systems with other areas. Conversely, more extensive
      network interactions are needed with core timing (striatum) and attention
      (superior parietal) centers to integrate time codes for intersensory signals.

PMID- 21847373
TI  - Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal
      Ganglia.
AB  - GABA transporter type 1 and 3 (GAT-1 and GAT-3, respectively) are the two main
      subtypes of GATs responsible for the regulation of extracellular GABA levels in
      the central nervous system. These transporters are widely expressed in neuronal
      (mainly GAT-1) and glial (mainly GAT-3) elements throughout the brain, but most
      data obtained so far relate to their role in the regulation of GABA(A) receptor
      mediated postsynaptic tonic and phasic inhibition in the hippocampus, cerebral
      cortex and cerebellum. Taking into consideration the key role of GABAergic
      transmission within basal ganglia networks, and the importance for these systems
      to be properly balanced to mediate normal basal ganglia function, we analyzed in
      detail the localization and function of GAT-1 and GAT-3 in the globus pallidus of
      normal and Parkinsonian animals, in order to further understand the substrate and
      possible mechanisms by which GABA transporters may regulate basal ganglia
      outflow, and may become relevant targets for new therapeutic approaches for the
      treatment of basal ganglia-related disorders. In this review, we describe the
      general features of GATs in the basal ganglia, and give a detailed account of
      recent evidence that GAT-1 and GAT-3 regulation can have a major impact on the
      firing rate and pattern of basal ganglia neurons through pre- and post-synaptic
      GABA(A)- and GABA(B)-receptor-mediated effects.

PMID- 21847375
TI  - The importance of reporting housing and husbandry in rat research.

PMID- 21847376
TI  - Analysis of kinase gene expression in the frontal cortex of suicide victims:
      implications of fear and stress.
AB  - Suicide is a serious public health issue that results from an interaction between
      multiple risk factors including individual vulnerabilities to complex feelings of
      hopelessness, fear, and stress. Although kinase genes have been implicated in
      fear and stress, including the consolidation and extinction of fearful memories,
      expression profiles of those genes in the brain of suicide victims are less
      clear. Using gene expression microarray data from the Online Stanley Genomics
      Database and a quantitative PCR, we investigated the expression profiles of
      multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK),
      the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the
      protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients
      died with suicide (N = 45) and without suicide (N = 38). We also investigated the
      expression pattern of the same genes in the PFC of developing humans ranging in
      age from birth to 49 year (N = 46). The expression levels of CAMK2B, CDK5, MAPK9,
      and PRKCI were increased in the PFC of suicide victims as compared to non-suicide
      controls (false discovery rate, FDR-adjusted p < 0.05, fold change >1.1). Those
      genes also showed changes in expression pattern during the postnatal development
      (FDR-adjusted p < 0.05). These results suggest that multiple kinase genes undergo
      age-dependent changes in normal brains as well as pathological changes in suicide
      brains. These findings may provide an important link to protein kinases known to
      be important for the development of fear memory, stress associated neural
      plasticity, and up-regulation in the PFC of suicide victims. More research is
      needed to better understand the functional role of these kinase genes that may be
      associated with the pathophysiology of suicide.

PMID- 21847377
TI  - Unraveling the differential functions and regulation of striatal neuron sub
      populations in motor control, reward, and motivational processes.
AB  - The striatum, the major input structure of the basal ganglia, is critically
      involved in motor control and learning of habits and skills, and is also involved
      in motivational and reward processes. The dorsal striatum, caudate-putamen, is
      primarily implicated in motor functions whereas the ventral striatum, the nucleus
      accumbens, is essential for motivation and drug reinforcement. Severe basal
      ganglia dysfunction occurs in movement disorders as Parkinson's and Huntington's
      disease, and in psychiatric disorders such as schizophrenia and drug addiction.
      The striatum is essentially composed of GABAergic medium-sized spiny neurons
      (MSNs) that are output neurons giving rise to the so-called direct and indirect
      pathways and are targets of the cerebral cortex and mesencephalic dopaminergic
      neurons. Although the involvement of striatal sub-areas in motor control and
      motivation has been thoroughly characterized, major issues remained concerning
      the specific and respective functions of the two MSNs sub-populations, D(2)R
      striatopallidal (dopamine D(2) receptor-positive) and D(1)R-striatonigral
      (dopamine D(1) receptor-positive) neurons, as well as their specific regulation.
      Here, we review recent advances that gave new insight in the understanding of the
      differential roles of striatopallidal and striatonigral neurons in the basal
      ganglia circuit. We discuss innovative techniques developed in the last decade
      which allowed a much precise evaluation of molecular pathways implicated in
      motivational processes and functional roles of striatopallidal and striatonigral
      neurons in motor control and in the establishment of reward-associated behavior.

PMID- 21847378
TI  - Human Scalp Electroencephalography Reveals that Repetition Suppression Varies
      with Expectation.
AB  - Repetitions of a sensory event elicit lower levels of brain activity than its
      initial presentation ("repetition suppression," RS). According to one view, RS
      depends on the biophysics of neuronal discharge, and is thus an automatic
      consequence of stimulus processing ("fatigue" model). Another account suggests
      that RS depends on the statistical structure of the environment, and occurs when
      repeated stimuli are less surprising than novel stimuli ("surprise reduction"
      model). In support of the latter view, functional magnetic resonance imaging
      studies have shown that RS is modulated by the local probability of repetition.
      However, single-cell recordings from macaque inferotemporal area (IT) have failed
      to replicate this finding. Here, we recorded scalp electroencephalography from
      human participants viewing pairs of faces that repeated (face(1)-face(1)) or
      alternated (face(1)-face(2)), in contexts in which repetitions were expected or
      unexpected. As previously described, event-related potentials in the range of 100
      400 ms recorded at posterior electrode sites and at the vertex differed between
      repetitions and alternations. Critically, at central electrodes, we observed that
      the difference between repeated and alternating stimuli was attenuated when
      repetitions were unexpected, as predicted by the surprise reduction model. These
      findings demonstrate that the modulation of RS by repetition probability is
      observable using direct neural recording methods in human participants, and that
      it occurs relatively late (>300 ms) post-stimulus. Finally, we found that theta
      band (4-8 Hz) spectral power over central electrodes varied with the three-way
      interaction between of repetition, expectation, and the rate of change of the
      environment, consistent with recent reports that frontal theta may be a hallmark
      of learning processes originating in the anterior cingulate and medial prefrontal
      cortex.

PMID- 21847379
TI  - Statistical analysis of multi-cell recordings: linking population coding models
      to experimental data.

PMID- 21847380
TI  - The retrosplenial cortex: intrinsic connectivity and connections with the
      (para)hippocampal region in the rat. An interactive connectome.
AB  - A connectome is an indispensable tool for brain researchers, since it quickly
      provides comprehensive knowledge of the brain's anatomical connections. Such
      knowledge lies at the basis of understanding network functions. Our first
      comprehensive and interactive account of brain connections comprised the rat
      hippocampal-parahippocampal network. We have now added all anatomical connections
      with the retrosplenial cortex (RSC) as well as the intrinsic connections of this
      region, because of the interesting functional overlap between these brain
      regions. The RSC is involved in a variety of cognitive tasks including memory,
      navigation, and prospective thinking, yet the exact role of the RSC and the
      functional differences between its subdivisions remain elusive. The connectome
      presented here may help to define this role by providing an unprecedented
      interactive and searchable overview of all connections within and between the rat
      RSC, parahippocampal region and hippocampal formation.

PMID- 21847381
TI  - Screening action potentials: the power of light.
AB  - Action potentials reflect the concerted activity of all electrogenic constituents
      in the plasma membrane during the excitation of a cell. Therefore, the action
      potential is an integrated read out and a promising parameter to detect
      electrophysiological failures or modifications thereof in diagnosis as well as in
      drug screens. Cellular action potentials can be recorded by optical approaches.
      To fulfill the pre-requirements to scale up for, e.g., pharmacological screens
      the following preparatory work has to be provided: (i) model cells under
      investigation need to represent target cells in the best possible manner; (ii)
      optical sensors that can be either small molecule dyes or genetically encoded
      potential probes need to provide a reliable read out with minimal interaction
      with the naive behavior of the cells and (iii) devices need to be capable to
      stimulate the cells, read out the signals with the appropriate speed as well as
      provide the capacity for a sufficient throughput. Here we discuss several
      scenarios for all three categories in the field of cardiac physiology and
      pharmacology and provide a perspective to use the power of light in screening
      cardiac action potentials.

PMID- 21847383
TI  - Overcoming selfishness: reciprocity, inhibition, and cardiac-autonomic control in
      the ultimatum game.
AB  - The processes underlying decision-making in response to unfair offers in the
      ultimatum game (UG) have recently been discussed in light of models of
      reciprocity and fairness-related behavior. It has been suggested that behavior
      following norm-oriented, internalized expectations of reciprocity requires
      overcoming economic self-interest. In this study we investigated both, behavioral
      and peripheral-physiological indicators of inhibitory capacity related to
      neuronal networks that are likely to be involved in the behavioral response to
      unfair offers. Both heart-rate variability as an index of inhibitory capacity,
      and performance in a motor response inhibition task predicted rejection of unfair
      offers in an UG, suggesting an important role of inhibitory processes in
      overcoming economic temptations and regulating behavior conforming to social
      norms of reciprocity and fairness. The role of parasympathetic activity as a
      physiological trait-marker predicting inter-individual differences in the
      rejection of unfair offers is discussed.

PMID- 21847382
TI  - The impact of childhood maltreatment: a review of neurobiological and genetic
      factors.
AB  - Childhood maltreatment represents a significant risk factor for psychopathology.
      Recent research has begun to examine both the functional and structural
      neurobiological correlates of adverse care-giving experiences, including
      maltreatment, and how these might impact on a child's psychological and emotional
      development. The relationship between such experiences and risk for
      psychopathology has been shown to vary as a function of genetic factors. In this
      review we begin by providing a brief overview of neuroendocrine findings, which
      indicate an association between maltreatment and atypical development of the
      hypothalamic-pituitary-adrenal axis stress response, which may predispose to
      psychiatric vulnerability in adulthood. We then selectively review the magnetic
      resonance imaging (MRI) studies that have investigated possible structural and
      functional brain differences in children and adults who have experienced
      childhood maltreatment. Differences in the corpus callosum identified by
      structural MRI have now been reliably reported in children who have experienced
      abuse, while differences in the hippocampus have been reported in adults with
      childhood histories of maltreatment. In addition, there is preliminary evidence
      from functional MRI studies of adults who have experienced childhood maltreatment
      of amygdala hyperactivity and atypical activation of frontal regions. These
      functional differences can be partly understood in the context of the information
      biases observed in event-related potential and behavioral studies of physically
      abused children. Finally we consider research that has indicated that the effect
      of environmental adversity may be moderated by genotype, reviewing pertinent
      studies pointing to gene by environment interactions. We conclude by exploring
      the extent to which the growing evidence base in relation to neurobiological and
      genetic research may be relevant to clinical practice and intervention.

PMID- 21847384
TI  - Anti-voice adaptation suggests prototype-based coding of voice identity.
AB  - We used perceptual aftereffects induced by adaptation with anti-voice stimuli to
      investigate voice identity representations. Participants learned a set of voices
      then were tested on a voice identification task with vowel stimuli morphed
      between identities, after different conditions of adaptation. In Experiment 1,
      participants chose the identity opposite to the adapting anti-voice significantly
      more often than the other two identities (e.g., after being adapted to anti-A,
      they identified the average voice as A). In Experiment 2, participants showed a
      bias for identities opposite to the adaptor specifically for anti-voice, but not
      for non-anti-voice adaptors. These results are strikingly similar to adaptation
      aftereffects observed for facial identity. They are compatible with a
      representation of individual voice identities in a multidimensional perceptual
      voice space referenced on a voice prototype.

PMID- 21847385
TI  - Authentic and play-acted vocal emotion expressions reveal acoustic differences.
AB  - Play-acted emotional expressions are a frequent aspect in our life, ranging from
      deception to theater, film, and radio drama, to emotion research. To date,
      however, it remained unclear whether play-acted emotions correspond to
      spontaneous emotion expressions. To test whether acting influences the vocal
      expression of emotion, we compared radio sequences of naturally occurring
      emotions to actors' portrayals. It was hypothesized that play-acted expressions
      were performed in a more stereotyped and aroused fashion. Our results demonstrate
      that speech segments extracted from play-acted and authentic expressions differ
      in their voice quality. Additionally, the play-acted speech tokens revealed a
      more variable F(0)-contour. Despite these differences, the results did not
      support the hypothesis that the variation was due to changes in arousal. This
      analysis revealed that differences in perception of play-acted and authentic
      emotional stimuli reported previously cannot simply be attributed to differences
      in arousal, but by slight and implicitly perceptible differences in encoding.

PMID- 21847387
TI  - The current role of vacuum assisted breast biopsy system in breast disease.
AB  - The gold standard for breast biopsy procedures is currently an open excision of
      the suspected lesion. However, an excisional biopsy inevitably makes a scar. The
      cost and morbidity associated with this procedure has prompted many physicians to
      evaluate less invasive, alternative procedures. More recently, image-guided
      percutaneous core-needle biopsy has become a frequently used method for
      diagnosing palpable and non-palpable breast lesions. Although sensitivity rates
      for core-needle biopsy are high, it has the disadvantage of histological
      underestimation, which renders the management of atypical ductal hyperplasia,
      papillary lesions, and fibroepithelial lesions somewhat difficult. Vacuum
      assisted breast biopsy (VABB) was developed to overcome some of these negative
      aspects of core-needle biopsy. VABB allows for a sufficient specimen to be
      obtained with a single insertion and can provide a more accurate diagnosis and
      completely remove the lesion under real-time ultrasonic guidance. The advantage
      of complete lesion removal with VABB is to reduce or eliminate sampling error, to
      decrease the likelihood of a histological underestimation, to decrease imaging
      histological discordance, to decrease the re-biopsy rate, and to diminish the
      likelihood of subsequent growth on follow-up. In recent years, with the
      advancement of VABB instruments and techniques, many outcome studies have
      reported on the use of VABB for resecting benign breast lesions with a curative
      intent. VABB is highly accurate for diagnosing suspicious breast lesions and is
      highly successful at treating presumed benign breast lesions. Thus, in the near
      future, VABB will be routinely offered to all appropriately selected patients.

PMID- 21847389
TI  - alphaB-Crystallin is a Novel Oncoprotein Associated with Poor Prognosis in Breast
      Cancer.
AB  - PURPOSE: alphaB-crystallin, a small heat shock protein, is an anti-apoptotic
      protein associated with aggressive tumor behavior. A recent study revealed that
      alphaB-crystallin is overexpressed in a metastatic variant of the GI101A human
      breast carcinoma cell line. The purpose of this study was to investigate whether
      alphaB-crystallin is related to other breast tumor markers and can predict a
      breast cancer prognosis. METHODS: Eighty-two patients who underwent breast cancer
      surgery at Hallym Sacred Heart Hospital were enrolled. alphaB-crystallin
      expression was determined by immunohistochemical staining. Estrogen receptor,
      progesterone receptor (PR), human epidermal growth factor receptor,
      lymphovascular invasion, histological grade, other tumor markers and time to
      recurrence were compared with alphaB-crystallin expression. RESULTS: alphaB
      crystallin expression in breast cancer tissues was associated with PR (p=0.030),
      the number of metastatic lymph nodes (pN) (p=0.020), lymphovascular invasion
      (p=0.022), histological grade (p=0.004) and triple negative breast cancer (TNBC)
      (p=0.004). alphaB-crystallin expression significantly decreased time to
      recurrence (p=0.039). CONCLUSION: The results revealed a strong relationship
      between alphaB-crystallin and poor prognostic factors such as the number of
      metastatic lymph nodes (especially pN2), TNBC, and rapid time to recurrence. We
      believe that alphaB-crystallin could be a novel oncoprotein biomarker of a poor
      prognosis in breast cancer.

PMID- 21847388
TI  - Silibinin enhances ultraviolet B-induced apoptosis in mcf-7 human breast cancer
      cells.
AB  - PURPOSE: Chemotherapies for breast cancer generally have strong cellular
      cytotoxicity and severe side effects. Thus, significant emphasis has been placed
      on combinations of naturally occurring chemopreventive agents. Silibinin is a
      major bioactive flavonolignan extracted from milk thistle with chemopreventive
      activity in various organs including the skin, prostate, and breast. However, the
      mechanism underlying the inhibitory action of silibinin in breast cancer has not
      been completely elucidated. Therefore, we investigated the effect of silibinin in
      MCF-7 human breast cancer cells and determined whether silibinin enhances
      ultraviolet (UV) B-induced apoptosis. METHODS: The effects of silibinin on MCF-7
      cell viability were determined using the MTT assay. The effect of silibinin on
      PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein
      expression in MCF-7 cells was analyzed using Western blot. The effect of
      silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry.
      RESULTS: A dose- and time-dependent reduction in viability was observed in MCF-7
      cells treated with silibinin. Silibinin strongly induced apoptotic cell death in
      MCF-7 cells, and induction of apoptosis was associated with increased p53
      expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells.
      CONCLUSION: Silibinin induced a loss of cell viability and apoptotic cell death
      in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an
      additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin
      might be an important supplemental agent for treating patients with breast
      cancer.

PMID- 21847390
TI  - Role of Estrogen Receptor-alpha in the Regulation of Claudin-6 Expression in
      Breast Cancer Cells.
AB  - PURPOSE: In our previous studies we showed that upregulating claudin-6 (CLDN6)
      expression may contribute to preventing breast cancer, and that 17beta-estradiol
      induces a concentration- and time-related effect on CLDN6 mRNA and protein
      expression in MCF-7 cells. However, the mechanisms of 17beta-estradiol regulation
      of CLDN6 are still unclear. We determined the role of estrogen receptors in the
      regulation of CLDN6 expression in human breast cancer tissues and a cell line.
      METHODS: CLDN6, estrogen receptor alpha (ERalpha) and estrogen receptor beta
      (ERbeta) expression in breast cancer tissues were examined using
      immunohistochemistry. The human breast cancer cell line, MCF-7, which expresses
      ERalpha but not ERbeta was used. CLDN6 and ERalpha expression were measured by
      reverse transcriptase-PCR, Western blotting and immunofluorescent staining.
      Treatments with propyl pyrazole triol (PPT) and ICI 182, 780 (ICI) were
      performed. RESULTS: The results revealed that CLDN6 expression was related to
      ERalpha in breast cancer tissues (p=0.033). PPT, an ERalpha-selective ligand,
      upregulated CLDN6 expression at 10(-5) mol/L after 24 hours. The effect of PPT on
      regulating CLDN6 expression in MCF-7 cells was blocked by ICI. CONCLUSION: These
      findings suggest that Eralpha reulates CLDN6 expression in breast cancer tissues
      and that 17beta-estradiol induces CLDN6 expression through an ERalpha pathway in
      MCF-7 cells.

PMID- 21847391
TI  - Incidental breast cancers identified in the one-stop symptomatic breast clinic.
AB  - PURPOSE: Breast cancers can be asymptomatic at an early stage and hence screening
      programmes play an important role in detecting breast cancers early. Even in
      those patients who present with breast symptoms, breast cancers may be present at
      a site remote to the site of symptoms. In this study, we aimed to assess the
      frequency, site and imaging modality used to identify these incidental cancers in
      the symptomatic one-stop breast clinic. METHODS: All patients who were seen in
      our breast clinic with breast symptoms over a two-year period were included in
      the study. We correlated the presenting symptoms of patients diagnosed with
      breast cancer with imaging (mammogram and ultrasound) findings. Incidental
      cancers were defined as "histologically confirmed breast cancers which were
      impalpable, remote to the site of symptoms and only identified on imaging."
      RESULTS: In the study period, 281 women were diagnosed with breast cancer out of
      4,400 patients seen at the one-stop breast clinic. Thirty six patients (12.8%)
      diagnosed with breast cancer had an incidental cancer which was only identified
      by imaging. The majority of contralateral, incidental cancers were identified by
      both mammography and ultrasound (US) and patients were all above 35 years.
      CONCLUSION: We suggest mammography of both breasts and US of the symptomatic
      breast in order to identify incidental cancers.

PMID- 21847386
TI  - Viral takeover of the host ubiquitin system.
AB  - Like the other more well-characterized post-translational modifications
      (phosphorylation, methylation, acetylation, acylation, etc.), the attachment of
      the 76 amino acid ubiquitin (Ub) protein to substrates has been shown to govern
      countless cellular processes. As obligate intracellular parasites, viruses have
      evolved the capability to commandeer many host processes in order to maximize
      their own survival, whether it be to increase viral production or to ensure the
      long-term survival of latently infected host cells. The first evidence that
      viruses could usurp the Ub system came from the DNA tumor viruses and
      Adenoviruses, each of which use Ub to dysregulate the host cell cycle (Scheffner
      et al., 1990; Querido et al., 2001). Today, the list of viruses that utilize Ub
      includes members from almost every viral class, encompassing both RNA and DNA
      viruses. Among these, there are examples of Ub usage at every stage of the viral
      life cycle, involving both ubiquitination and de-ubiquitination. In addition to
      viruses that merely modify the host Ub system, many of the large DNA viruses
      encode their own Ub modifying machinery. In this review, we highlight the latest
      discoveries regarding the myriad ways that viruses utilize Ub to their advantage.

PMID- 21847392
TI  - The 70-gene prognostic signature for korean breast cancer patients.
AB  - PURPOSE: A 70-gene prognostic signature has prognostic value in patients with
      node-negative breast cancer in Europe. This diagnostic test known as
      "MammaPrintTM (70-gene prognostic signature)" was recently validated and
      implementation was feasible. Therefore, we assessed the 70-gene prognostic
      signature in Korean patients with breast cancer. We compared the risk predicted
      by the 70-gene prognostic signature with commonly used clinicopathological
      guidelines among Korean patients with breast cancer. We also analyzed the 70-gene
      prognostic signature and clinicopathological feature of the patients in
      comparison with a previous validation study. METHODS: Forty-eight eligible
      patients with breast cancer (clinical T1-2N0M0) were selected from four hospitals
      in Korea. Fresh tumor samples were analyzed with a customized microarray for the
      70-gene prognostic signature. Concordance between the risk predicted by the 70
      gene prognostic signature and risk predicted by commonly used clinicopathological
      guidelines (St. Gallen guidelines, National Institutes of Health [NIH] guideline,
      and Adjuvant! Online) was evaluated. RESULTS: Prognosis signatures were assessed
      in 36 patients. No significant differences were observed in the
      clinicopathological features of patients compared with previous studies. The 70
      gene prognosis signature identified five (13.9%) patients with a low-risk
      prognosis signature and 31 (86.1%) patients with a high-risk prognosis signature.
      Clinical risk was concordant with the prognosis signature for 29 patients (80.6%)
      according to the St. Gallen guidelines; 30 patients (83.4%) according to the NIH
      guidelines; and 23 patients (63.8%) according to the Adjuvant! Online. Our
      results were different from previous validation studies in Europe with about a
      40% low-risk prognosis and about a 60% high-risk prognosis. The high incidence in
      the high-risk group was consistent with data in Japan. CONCLUSION: The results of
      70-gene prognostic signature of Korean patients with breast cancer were somewhat
      different from those identified in Europe. This difference should be studied as
      whether there is a gene disparity between Asians and Europeans. Further large
      scale studies with a follow-up evaluation are required to assess whether the use
      of the 70-gene prognostic signature can predict the prognosis of Korean patients
      with breast cancer.

PMID- 21847393
TI  - Prognostic Factors in Patients with Stage II/III Breast Cancer Treated with
      Adjuvant Extension of Neoadjuvant Chemotherapy: A Retrospective Cohort Study with
      Ten-Years of Follow-Up Data.
AB  - PURPOSE: The aim of this retrospective study was to identify the reliable long
      term prognostic factors in patients with stage II/III breast cancer who were
      treated with an adjuvant extension of neoadjuvant chemotherapy (NC). METHODS:
      Women under the age of 70-years, with previously untreated clinical stage II and
      III breast cancer, were treated with NC, which was comprised of three cycles of
      FEC (5-FU, epirubicin, and cyclophosphamide every 3 weeks) or MMM (methotrexate,
      mitoxantrone, and mitomycin-C every 3 weeks) with an adjuvant extension of three
      cycles of the same regimen. RESULTS: Cumulative 10-years disease-free survival
      (DFS) was 87.3% for patients with a good response and 55.5% for patients with no
      response (p=0.032); 92.9% for node negative patients, 75.0% for 1-3 positive
      nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes
      (p<0.001). Cumulative 10-years overall survival (OS) was 89.1% for patients with
      good response and 55.5% for patients with no response (p=0.024); 95.2% for node
      negative patients, 80.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and
      no survival for 10 or more positive nodes (p<0.001). No significant difference
      was observed in DFS and OS between the FEC and MMM treated groups. CONCLUSION:
      Based on a review of data with a long follow-up, only the clinical response to NC
      and the absolute number of metastatic axillary lymph node identified at surgical
      staging were independent predictors of both DFS and OS in patients with stage
      II/III breast cancer patients treated with adjuvant extension of NC.

PMID- 21847394
TI  - Patterns of recurrence after breast-conserving treatment for early stage breast
      cancer by molecular subtype.
AB  - PURPOSE: To study clinical features and patterns of recurrence after breast
      conserving treatment (BCT) for three molecular subtypes of early stage breast
      cancer. METHODS: The sample studied included 596 patients with T1-2N0-1 breast
      cancer who received BCT. Three groups were defined by receptor status. Luminal:
      estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative
      (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative;
      and HER2 overexpressing: ER and PR negative but HER2 receptor positive. RESULTS:
      The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83
      (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2
      subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and
      poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up
      period, locoregional recurrence was detected as the first site of recurrence in
      26 (6.4%), 11 (10.5%), and 9 (10.8%) patients in the luminal, TN, and HER2
      subtypes, respectively (p=0.1924). Thirty-one (7.6%), 7 (6.7%), and 7 (8.4%)
      patients in each group had distant metastases as the first sign of recurrence
      (p=0.8996). Median time to locoregional and distant recurrence was shorter in the
      HER2 subtype (p=0.0889 and 0.0780, respectively), and the HER2 subtype was
      significantly associated with poor overall survival (p=0.0009). CONCLUSION: After
      BCT in Korean women with early stage breast cancer, the patterns of recurrence
      were not different among the molecular subtypes, although the TN and HER2
      subtypes were associated with younger age, higher nuclear grade, and poorer
      histologic grade.

PMID- 21847395
TI  - The feasibility of endoscopy-assisted breast conservation surgery for patients
      with early breast cancer.
AB  - PURPOSE: Breast conservation surgery (BCS) has become a standard treatment method
      for patients with early breast cancer. Endoscopy-assisted BCS (EABCS) can be
      performed through an inconspicuous periareolar and a small axillary incision for
      sentinel node biopsy, which may give better cosmetic outcomes than conventional
      BCS skin incisions. This study was designed to evaluate the feasibility of EABCS
      for patients with early breast cancer. METHODS: Forty-three patients were
      candidates for EABCS, and EABCS was performed in 40 patients with breast cancer
      between January 2008 and July 2010. Their clinicopathological features were
      retrospectively analyzed. Operative time, margin status, complications, and
      relapse-free survival were compared with those of patients treated by
      conventional BCS and who were treated at the same institute during the same
      period. RESULTS: The most common lesion site of the EABCS and conventional BCS
      groups was the upper area of the breast. Tumor size in all patients was less than
      4 cm (range, 0.4-3.7 cm), and nodal involvement was found in eight (20%) patients
      in the BCS group. The mean operative time was 110 minutes for the EABCS group and
      107 minutes for the conventional BCS group, and those were not significantly
      different. No significant difference in frozen or final margin status was
      observed between the EABCS and conventional BCS groups. Relapse-free survival was
      statistically equivalent between the groups with a median follow-up of 12 months.
      Postoperative complications occurred in five cases in four patients with EABCS,
      which was not significantly different from conventional BCS. CONCLUSION:
      Performing EABCS in patients with early breast cancer seems to be feasible and
      safe. Further study with a longer-term follow-up may be needed to confirm the
      clinical value of EABCS.

PMID- 21847396
TI  - Comparing scalpel, electrocautery and ultrasonic dissector effects: the impact on
      wound complications and pro-inflammatory cytokine levels in wound fluid from
      mastectomy patients.
AB  - PURPOSE: Introducing the relationship between the surgical instruments used in
      modified radical mastectomy and wound complications is important for preventing
      and decreasing complications. This prospective randomized trial was designed to
      assess the impact of scalpel, electrocautery, and ultrasonic dissector usage on
      wound complications and tissue damage. METHODS: Eighty-two consecutive patients
      operated with mastectomy were studied. The postoperative time period needed for
      hemovac drainage, the amount and duration of seroma, infection, flap ecchymosis
      and necrosis rates were compared. Tumor necrosis factor alpha (TNF-alpha) and
      interleukin-6 (IL-6) levels in drainage fluids were determined to confirm the
      inflammatory response and tissue damage. RESULTS: The numbers of patients
      included in the scalpel, electrocautery and ultrasonic dissector groups were 27,
      26, and 29, respectively. The groups were homogenous with respect to age, body
      mass index, stage, cormorbidities, breast volume and flap area. Operation time
      and the amount of bleeding were statistically higher in the scalpel group. The
      incidence of seroma was higher in the electrocautery group and arm mobilization
      had to be delayed in this group. There were no differences between groups with
      respect to hematoma, infection, ecchymosis, necrosis, hemovac drainage and the
      total and first 3 days of seroma volume. TNF-alpha and IL-6 levels were
      significantly higher in samples obtained from the drains of patients operated
      with electrocautery. CONCLUSION: Ultrasonic dissector decreases operation time by
      decreasing the amount of bleeding without increasing the seroma incidence. High
      cytokine levels in drainage fluids from patients operated with elecrocautery
      indicates that electrocautery induces more tissue damage and acute inflammatory
      response. Therefore, seroma, due to acute inflammatory response, was seen more
      frequently in the electrocautery group. Ultrasonic dissector coagulates protein
      by breaking hydrogen bonds which may close vascular and lymphatic channels more
      precisely. But, its actual preventive effect on seroma formation might be related
      to diminished inflammatory response.

PMID- 21847397
TI  - Lateral decubitus positioning stereotactic vacuum-assisted breast biopsy with
      true lateral mammography.
AB  - Stereotactic vacuum-assisted breast biopsy (VAB) has been used to evaluate
      microcalcifications or non-palpable breast lesions on mammography. Although
      stereotactic VAB is usually performed in a prone or upright position, an
      expensive prone table is necessary and vasovagal reactions often occur during the
      procedure. For these reasons, the lateral decubitus position can be applied for
      stereotactic VAB, and true lateral mammography can be used to detect the lesion.
      We report on 15 cases of lateral decubitus positioning for stereotactic VAB with
      true lateral mammography for non-palpable breast lesions or microcalcifications.
      The mean procedure time was approximately 30.1 minutes, and no complications
      occurred during the procedures. Fourteen cases had benign breast lesions and one
      case had a ductal carcinoma in situ. The lateral decubitus stereotactic VAB with
      true lateral mammography can be applied for microcalcifications or non-palpable
      breast lesions and helps to minimize anxiety and vasovagal reactions in patients.

PMID- 21847398
TI  - Solitary small bowel metastasis from breast cancer.
AB  - The common sites of metastasis of breast cancer are bone, lung, and liver, but
      gastrointestinal metastasis from breast cancer is rare. We experienced a case of
      solitary ileal metastasis from breast cancer. A 45-years-old woman presented with
      melena for several weeks. She showed no other abdominal symptoms. Colonoscopy
      findings showed an ulcerative mucosal lesion in the terminal ileum, and biopsy
      was performed. Pathologic examination revealed metastatic carcinoma, originated
      from breast. The tumor cells were positive for estrogen receptor and negative for
      Cdx-2. She had had a previous medical history of bilateral breast cancer and
      undergone breast conserving surgery with sentinel lymph node biopsy for both
      breasts. The torso positron emission tomography scan at 19 months after surgery
      showed mildly increased uptake in the terminal ileum which was considered as
      inflammation. Finally, she was diagnosed with solitary ileal metastasis from
      breast cancer at 22 months after surgery.

PMID- 21847399
TI  - Microglandular adenosis.
AB  - Microglandular adenosis (MGA) of the breast is a very rare and benign
      proliferative lesion. Most patients complain of a palpable breast mass that may
      arouse a clinical suspicion of breast cancer. Histopathologically, it is hard to
      distinguish MGA from breast cancer because of the lack of a myoepithelial layer
      and infiltrative proliferation. Several studies have reported a strong
      relationship between MGA and carcinoma arising in MGA, so the mass should be
      excised completely in cases of MGA determined from a core needle biopsy rather
      than observation. A 72-years-old woman presented with a palpable breast mass. On
      physical examination, a mass was palpable in the right upper outer quadrant area
      and somewhat fixed to the surrounding tissues and pectoralis major muscle. We
      could not detect any mass or dense lesion on mammography because of a grade 4
      dense breast. Ultrasonographic findings revealed a low echoic lesion with
      indistinct margins. The result of a core needle biopsy was MGA, which was
      confirmed by excision. We report one case of MGA, which was believed to breast
      cancer clinically.

PMID- 21847400
TI  - Invited Commentary: Role of Estrogen Receptor-alpha in Regulating Claudin-6
      Expression in Breast Cancer Cells.

PMID- 21847401
TI  - Risk factors and control strategies for the rapidly rising rate of breast cancer
      in Korea.
AB  - Due to the aging population and tremendous changes in life style over the past
      decades, cancer has been the leading cause of death in Korea. The incidence rate
      of breast cancer is the second highest in Korea, and it has shown an annual
      increase of 6.8% for the past 6 years. The major risk factors of breast cancer in
      Korean women are as follows: Early menarche, late menopause, late full-term
      pregnancy (FTP), and low numbers of FTP. Height and body mass index increased the
      risk of breast cancer in postmenopausal women only. There are ethnic variations
      in breast cancer due to the differences in genetic susceptibility or exposure to
      etiologic agent. With the epidemiological evidences on the possibility of further
      increase of breast cancer in Korea, the Korean Government began implementing the
      National Cancer Screening Program against breast cancer in 2002. Five-year
      survival rates for female breast cancer have improved significantly from 78.0% in
      early 1993-1995 to 90.0% in 2004-2008. This data indicate that improvement of the
      survival rate may be partially due to the early diagnosis of breast cancer as
      well as the increased public awareness about the significance of early detection
      and organized cancer screening program. The current primary prevention programs
      are geared towards strengthening national prevention campaigns. In accordance
      with the improvement in 5-year survival rate, the overall cancer mortality has
      started to decrease. However, breast cancer death rate and incidence rates are
      still increasing, which need further organized effort by the Korean Government.

PMID- 21847402
TI  - Overexpression of MMP-9 and HIF-1alpha in Breast Cancer Cells under Hypoxic
      Conditions.
AB  - PURPOSE: Hypoxia, which is a loss of oxygen in tissues, is a common condition in
      solid tumors due to the tumor outgrowing existing vasculature. Under hypoxic
      conditions, hypoxia-inducible factor (HIF)-1alpha rapidly accumulates and
      transactivates hundreds of genes, such as matrix metalloproteinases (MMPs). MMPs
      contribute to invasion and metastasis of tumor cells by degrading the surrounding
      basement membrane and extracellular matrix barriers, which enables the easy
      migration and spread of cancer cells. We examined whether hypoxia increases tumor
      cell invasion, and whether increased invasiveness was due to HIF-1alpha and MMP-9
      expression. METHODS: Transwell invasion assays were performed to demonstrate
      whether hypoxia enhance tumor invasion by use of MDA-MB-231 breast cancer cells.
      An immunofluorescence assay was used to demonstrate expression of HIF-1alpha and
      MMP-9 under hypoxic conditions. Luciferase and ChiP assays were performed to
      demonstrate that MMP-9 promoter activity was regulated by HIF-1alpha. RESULTS:
      HIF-1alpha was stabilized under hypoxic conditions and stimulated MMP-9
      expression, which affected the tumor invasiveness of breast cancer cells. HIF
      1alpha transactivated the MMP-9 promoter by forming a transcriptional unit with
      p300, thus increasing expression of MMP-9 transcripts. Zymography indicated that
      MMP-9 had more gelatinase activity under hypoxic conditions than normoxic
      conditions. Furthermore, the small GTPase Ras was also activated in response to
      hypoxia, which then aids stabilization of HIF-1alpha, and in turn upregulates MMP
      9 expression. We also demonstrate that MMP-9 is upregulated concurrently with HIF
      1alpha in tumor tissues from patients with breast cancer. CONCLUSION: These
      results suggest that HIF-1alpha promotes cell invasion through a MMP-9-dependent
      mechanism and that future antitumor agents could be used to target HIF-1alpha and
      MMP-9.

PMID- 21847403
TI  - Expression of leptin, leptin receptor, adiponectin, and adiponectin receptor in
      ductal carcinoma in situ and invasive breast cancer.
AB  - PURPOSE: Adipocytokines, such as leptin, resistin, and adiponectin, are
      associated with obesity and breast cancer. Several studies have indicated that
      adipocytokines may influence tumor growth or differentiation. The aims of this
      study were to determine the expression of leptin, leptin receptor (ObR),
      adiponectin and adiponectin receptor (AdipoR) in human breast cancer, to evaluate
      their prognostic significance in the breast cancer. METHODS: Specimens from 198
      patients with primary breast cancer were enrolled, and representative paraffin
      tumor blocks were selected for constructing tissue microarrarys (TMA).
      Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was
      performed using TMA, and the clinicopathologic characteristics were evaluated
      from the patient's medical records. RESULTS: Stage 0 breast cancer accounted for
      41 cases, and 157 cases were invasive cancer. Positive rates of leptin and ObR
      expression in the ductal carcinoma in situ (DCIS) group were significantly higher
      than those of the invasive cancer group (97.4% vs. 34.0%, p<0.001; 74.4% vs.
      29.8%, p<0.001). However, positive rates of adiponectin and AdipoR expression in
      the invasive cancer group were significantly higher than those in the DCIS group
      (53.7% vs. 33.3%, p=0.024; 59.9% vs. 26.3%, p<0.001). High leptin expression was
      significantly associated with high Ki-67 expression (p=0.016). High adiponectin
      expression was significantly correlated with smaller tumor size (p=0.001).
      CONCLUSION: We suggest that losses of leptin and ObR expression could be
      associated with invasive cancer, whereas high adiponectin and AdipoR expression
      may be associated with breast cancer invasiveness.

PMID- 21847404
TI  - D2-40, Podoplanin, and CD31 as a Prognostic Predictor in Invasive Ductal
      Carcinomas of the Breast.
AB  - PURPOSE: Distant metastasis and recurrence are major prognostic factors
      associated with breast cancer. Both lymphovascular invasion (LVI) and blood
      vessel invasion (BVI) are important routes for metastasis to regional lymph nodes
      and for systemic metastasis. Despite the importance of vascular invasion as a
      prognostic factor, application of vascular invasion as a histopathological
      criterion is controversial. The aim of this study was to distinguish LVI from BVI
      in prognosis and recurrence of breast cancer using an endothelial subtype
      specific immunohistochemical stain (podoplanin, D2-40, and CD31). METHODS:
      Sections from 80 paraffin-embedded archival specimens of invasive breast cancer
      were stained for podoplanin, D2-40, or CD31 expression. Immunohistochemical
      staining results were correlated with clinicopathological features, such as tumor
      size, status of lymph node metastases, estrogen receptor status, progesterone
      receptor status, human epidermal growth factor receptor-2 expression, and
      recurrence. Patients with ductal carcinoma in situ and stage IV breast cancer
      were excluded. RESULTS: A significant correlation was found between D2-40 LVI
      positivity and lymph node metastasis (p=0.022). We found a significant
      correlation between D2-40 LVI positivity and recurrence of breast cancer
      (p=0.014). However, no significant correlation was found between BVI and
      recurrence. A poorer disease free survival was shown for D2-40 positive LVI
      (p=0.003). In a multivariate analysis, the presence of D2-40 LVI positivity
      revealed a significant association with decreased disease-free survival.
      CONCLUSION: D2-40 LVI positivity was a more prognostic predictor of breast cancer
      than BVI.

PMID- 21847405
TI  - Quality of Life Differences between Younger and Older Breast Cancer Patients.
AB  - PURPOSE: This study was designed to investigate quality of life (QOL) differences
      between younger (<50 years) and older (>=50 years) breast cancer survivors and to
      determine the unique effect of age on QOL after adjusting age-correlated
      variables. METHODS: One thousand two hundred fifty patients were enrolled.
      Clinicopatholgical and social parameters were reviewed and Functional Assessment
      of Cancer Therapy-Breast cancer instrument (FACT-B) and the Ladder of Life scale
      were used to measure the QOL. Among 1,250 eligible patients, 1,094 patients
      completed the questionnaire and were used for analysis. Chi-square test, t-test
      and a series of multiple regression analyses were conducted to verify age-related
      differences in QOL between two groups and to evaluate the unique contribution of
      age variable on QOL of breast cancer patients. RESULTS: Significant socio
      demographic and clinical differences existed based on age categories, including
      education, job, time since surgery, chemotherapy and daily activity. Also, there
      were significant age-related differences in FACT-B total, physical well-being,
      social/family well-being, functional well-being and breast cancer subscale and in
      subjective QOL. Older patients >=50 years showed significantly lower QOL than
      younger patients <50 years. However, after controlling for age-correlated
      variables including job, education, time since surgery, chemotherapy, and daily
      activity, there was no unique age difference in QOL among breast cancer
      survivors. CONCLUSION: Our study results suggest that older women with breast
      carcinoma suffered significantly lower QOL, even though the unique age effect was
      not found. Therefore, various interventions for enhancing QOL for women with
      breast carcinoma should be provided to older age group.

PMID- 21847406
TI  - Ultrasound and clinicopathological characteristics of triple receptor-negative
      breast cancers.
AB  - PURPOSE: Triple receptor-negative (TRN) breast cancer is associated with high
      risk of recurrence and poor prognosis. The present study assessed the
      clinicopathologic characteristics and ultrasound (US) features of TRN breast
      cancers. METHODS: Pathological and biological data were reviewed for 558 breast
      cancer patients treated at Kangbuk Samsung Hospital, between January 2003 and
      December 2009. The patients were separated into TRN breast cancer and non-TRN
      breast cancer groups, based on the results of immunohistochemical prognostic
      panels. Clinical and pathologic features were compared for the two groups. US
      features, including shape, orientation, margins, boundaries, echo patterns,
      posterior acoustic features, surrounding tissues, and microcalcifications, were
      determined for 41 TRN patients and 189 non-TRN controls (ER+/PR+/HER2-). RESULTS:
      Of 558 cases, 58 (10.4%) had the TRN phenotype. Four hundred and thirty-four
      cases (77.8%) were invasive ductal carcinomas. TRN cancer was significantly
      associated with specific characteristics of tumor size, nuclear grade, histologic
      grade, venous invasion, and lymphatic invasion. With respect to US features, TRN
      cancers were more likely to have an oval shape, a circumscribed margin, and
      marked hypoechogenicity. CONCLUSION: Tumor characteristics were different between
      TRN and non-TRN breast cancers, although US cannot differentiate the subtype of
      breast cancers TRN cancer tend to show somewhat different US morphology.

PMID- 21847407
TI  - Tumor characteristics influencing non-sentinel lymph node involvement in
      clinically node negative patients with breast cancer.
AB  - PURPOSE: The negative sentinel lymph node (SLN) biopsy avoids conventional
      axillary dissection in patients with breast cancer with clinically negative
      axilla. Despite negative SLN, there is a risk of leaving involved non-SLN behind
      in the axilla. We investigated the predictive power of tumor characteristics for
      non-SLN metastasis. METHODS: Lymphatic mapping with blue dye method for SLN
      biopsy and level 1-2 axillary dissections were performed to establish axillary
      status in 59 patients with T1 and T2 breast cancer and clinically negative
      axilla. Tumor's characteristics were histopathologically established to assess
      their association with non-SLN metastasis. RESULTS: The axilla was malignant in
      23 (39%) patients. The SLN alone was metastatic in 10, both SLN and non-SLN in 9,
      and non-SLN alone in 4 (7%) patients. The false negative rate for SLN biopsy was
      10% in our series. The rate of positive non-SLN was found as 0% in T1a-b, 19% in
      T1c, and 40% in T2 tumors (p=0.035). Lymphovascular invasion was positive in 14
      (61%) patients with axillary metastasis (p<0.001), and in 10 (77%) patients with
      non-SLN involvement (p<0.001). CONCLUSION: We concluded that there was a small
      risk of involved non-SLN despite negative SLN. Tumor size (near or greater than 2
      cm) was significantly associated with non-SLN metastasis. Peritumoral
      lymphovascular invasion was a positive predictor of the metastatic involvement in
      non-SLNs.

PMID- 21847408
TI  - Comparison of Doxorubicin plus docetaxel neoadjuvant chemotherapy with
      Doxorubicin plus vinorelbine in primary breast cancer.
AB  - PURPOSE: This study was performed to compare the therapeutic efficacy and
      toxicity of doxorubicin plus docetaxel neoadjuvant chemotherapy (NC) with
      doxorubicin plus vinorelbine NC. METHODS: Fifty-three patients underwent 4 cycles
      of NC consisted of intravenous injection of doxorubicin (50 mg/m(2)) plus
      docetaxel (75 mg/m(2)) administered every 3 weeks (AD), while 49 patients
      underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50
      mg/m(2)) and vinorelbine (25 mg/m(2)) administered every 3 weeks (AN). Response
      rate and treatment-related toxicities were analyzed by administered
      chemotherapeutics. Response to NC was also analyzed according to
      clinicobiological characteristics of the primary tumors. RESULTS: Clinical
      response was observed in 66% with AN and 81.6% with AD chemotherapy. A complete
      pathologic response (pCR) was confirmed in 6 patients (11.3%) with AN and in 7
      patients (14.3%) with AD after the surgery. Response rate was significantly
      higher in AD compared with AN (p=0.038), but there was no significant difference
      between the two group regard to pCR rate. Breast conserving surgery (BCS) was
      performed in 35.8% of AN group, whereas 20 patients (40.8%) of AD group underwent
      BCS. The patients with HER2-amplified tumor showed significantly increased
      response to both types of NC. Pathologic complete response was confirmed in 9
      (39.1%) out of 23 HER2-amplified tumors, whereas only 4 (5.1%) of 79 HER2
      nonamplified tumors showed pathologic complete response. Febrile neutropenia
      occurred in 22.6% of total 212 cycles in AN and 38.8% of total 196 cycles in AD.
      Grade 3/4 neutropenia was observed in 39.6% in AN and 43.9% in AD. Grade 3
      mucositis was observed in 26.4% with AN and in 40.8% with AD. CONCLUSION: There
      was no significant increase of pCR by AD compared with AN. Long-term follow-up
      results of our study indicate that clinical outcome after NC was significantly
      associated with initial response to NC regardless of therapeutic regimens.

PMID- 21847409
TI  - Efficacy of fulvestrant in heavily pretreated postmenopausal women with advanced
      breast cancer: a preliminary report.
AB  - PURPOSE: Fulvestrant, a potent estrogen receptor (ER) antagonist with a novel
      mechanism of action, has shown efficacy in pretreated patients with advanced
      breast cancer. We assessed the efficacy and tolerability of fulvestrant in Korean
      postmenopausal women. METHODS: Of the 25 candidates identified at Asan Medical
      Center, Seoul, Korea, six were deemed ineligible due to inadequate baseline and
      follow-up imaging. The 19 patients included in this retrospective analysis
      received the approved dose of fulvestrant (250 mg intramuscular injection, once
      per month) as second- (n=8), third- (n=7), or fourth-line (n=4) endocrine
      therapy. RESULTS: At a median follow-up of 7.4 months (range, 1.2-34.8 months),
      the 19 patients received a median of four cycles (range, 1-34 cycles) of
      fulvestrant. Median time to progression was 5.5 months (95% confidence interval
      [CI], 0.4-10.7 months), and median overall survival was 17.9 months (95% CI, 2.7
      33.1 months). Among 17 evaluable patients, one (5.3%) achieved a partial
      response, 10 (52.6%) showed stable disease, and six (31.6%) showed progressive
      disease. The clinical benefit rate was 26.3%. Four patients (21.1%) reported
      adverse events, but all were grade 1 or 2. CONCLUSION: Fulvestrant was effective
      and well tolerated in patients with advanced breast cancer who had been
      previously treated with several lines of endocrine and chemotherapeutic agents.

PMID- 21847410
TI  - Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic
      Breast Cancer Pretreated with Anthracyclines and Taxanes.
AB  - PURPOSE: The role of first-line trastuzumab-based therapy has been firmly
      established in patients with human epidermal growth factor receptor-2 (HER2)
      positive metastatic breast cancer. In this trial, we evaluated the efficacy and
      safety of a vinorelbine and trastuzumab combination chemotherapy in patients who
      were pretreated with anthracyclines and taxanes. METHODS: Thirty-three patients
      with HER2 overexpressing metastatic breast cancer, all of whom had previously
      been treated with anthracyclines and taxanes, were included in this study. The
      patients were treated with 25 mg/m(2) of vinorelbine (over a 15-minute infusion)
      on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an
      initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at
      weekly doses of 2 mg/kg (over 30 minutes). RESULTS: The median age of the
      patients was 53 years (range, 39-72 years). The overall response rate was 30.3%
      (10 patients; 95% confidence interval [CI], 23-57%). The median time to
      progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival
      was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the
      incidence rates of grade >=3 neutropenia and anemia were 7.2% and 1.0%,
      respectively. Neutropenic fever was detected in three cycles (1.5%). The non
      hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was
      detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of
      the patients experienced any serious cardiac toxicity, and no treatment-related
      deaths occurred. CONCLUSION: These results show that a combination chemotherapy
      consisting of vinorelbine and trastuzumab is useful in patients with HER2
      overexpressing metastatic breast cancer who were pretreated with anthracyclines
      and taxanes, with a favorable toxicity profile.

PMID- 21847412
TI  - Ectopic hidradenoma papilliferum of the breast: ultrasound finding.
AB  - Hidradenoma papilliferum (HP) is a benign neoplasm arising from mammary-like
      glands which typically involves the dermal layer of the female anogenital area.
      The prognosis for HP is good. Recurrence is unusual and is typically attributed
      to incomplete excision of the primary tumor. Malignant transformation is rare and
      HP of the breast has not yet been reported. Ectopic HP is usually solitary,
      small, and asymptomatic. It appears as a well-circumscribed, complex cystic mass
      in the dermis on ultrasound. We present a case of HP arising from the axillary
      tail of the breast.

PMID- 21847411
TI  - Feasibility of sentinel lymph node biopsy in breast cancer patients with initial
      axillary lymph node metastasis after primary systemic therapy.
AB  - PURPOSE: Primary systemic therapy (PST) downstages up to 40% of initial
      documented axillary lymph node (ALN) metastases in breast cancer. The current
      surgical treatment after PST consists of breast tumor resection and axillary
      lymph node dissection (ALND). This strategy, however, does not eliminate
      unnecessary ALND in patients with complete remission of axillary metastases. The
      aim of this study was to examine the accuracy of sentinel lymph node biopsy
      (SLNB) after PST among patients with documented ALN metastasis at presentation
      and to identify the rate of pathologic complete-remission (CR) with ALN after
      PST. METHODS: We analyzed 66 patients with ALN metastasis that was pathologically
      proven preoperatively who underwent SLNB and concomitant ALND after PST. Axillary
      ultrasound (AUS) was used to evaluate the clinical response of initially
      documented ALN metastasis after PST. Intraoperative lymphatic mapping was
      performed using blue dye with or without radioisotope. RESULTS: After PST, 34.8%
      of patients had clinical CR of ALN on AUS and 28.8% patients had pathologic CR of
      ALN. The overall success rate of SLNB after PST was 87.9%, and the sentinel lymph
      node identification rate in patients with clinical CR was 95.7%. In patients with
      successful lymphatic mapping, 70.7% of patients had residual axillary metastases.
      The overall accuracy and false-negative rate were 87.9% and 17.1% in all
      patients: 95.5% and 10.0% in patients with clinical CR of ALN, and 83.3% and
      19.4% in patients with residual axillary disease after PST. CONCLUSION: Our
      findings suggest that SLNB may be feasible in patients with initial documented
      ALN metastasis who have clinical CR for metastatic ALN after PST. Further
      investigation in a prospective setting should be performed to confirm our
      results.

PMID- 21847413
TI  - Primary fibrosarcoma of the breast: a case report.
AB  - A primary fibrosarcoma of the breast is a rare tumor. Here we report on a case of
      a primary fibrosarcoma of the breast that presented as a palpable left breast
      mass in a 47-year-old woman. The physical examination revealed a 3 cm sized,
      round mass in the left upper outer breast. The mammograms revealed a 3 cm sized,
      partially circumscribed and partially obscured, high density mass in the upper
      outer quadrant of the left breast. An ultrasonogram demonstrated a 3 cm sized,
      ovoid, circumscribed and hypoechoic mass with peripheral increased vascularity on
      Doppler imaging. Surgical excision was performed and the pathology revealed a low
      grade fibrosarcoma.

PMID- 21847414
TI  - Primary acinic cell carcinoma of the breast: a case report with an
      immunohistochemical and ultrastructural studies.
AB  - Acinic cell carcinoma (ACC) of the breast is extremely rare and is characterized
      by widespread acinar cell-like differentiation. We report of a 39-year-old woman
      presented with a palpable breast mass with significant morphological,
      immunohistochemical and ultrastructural findings. Histologically, ACC showed a
      diffuse glandular infiltrative pattern, with small acinar or glandular structures
      mixed with solid nests. Neoplastic cells were monotonous proliferation of cells
      with a granular or clear cytoplasm, resembling acinar cells of the salivary
      glands or Paneth cells. Both glandular and solid tumor cell populations were
      strongly positive for lysozyme and alpha-1-antitrypsin.

PMID- 21847415
TI  - Commentary on: Incidental Breast Cancers Identified in a One-Stop Symptomatic
      Breast Clinic.

PMID- 21847416
TI  - Migrating Filshie clip.

PMID- 21847417
TI  - Congenital cataract and congenital chloride diarrhoea-a unique combination and
      antenatal diagnosis.
AB  - Congenital chloride diarrhoea (CCD) is a serious inherited defect of intestinal
      electrolyte absorption transmitted in an autosomal recessive way. The molecular
      pathology involves an epithelial Cl(-)/HCO(3)(-) exchanger protein, encoded by
      the solute carrier family 26 member 3 gene (SLC26A3) and known DRA (down
      regulated in adenomas) in the distal ileum and colon. Polyhydramnios, premature
      birth, ileus without meconium passage, hypochloremia, and hyponatremia are
      typical features of CCD in the neonate followed by chronic metabolic alkalosis,
      hypokalemia, hypochloremia, retarded growth and renal impairment in older
      children and adults if the disease is not adequately treated. Antenatal diagnosis
      if made on the basis of findings on ultrasonography-a non-invasive diagnostic
      test-can help in early management of the disorder immediately after birth and,
      thus, prevent the sequelae. We present an interesting case of CCD diagnosed
      antenatally and found to have congenital cataract, which is a unique occurrence
      not reported in literature so far.

PMID- 21847418
TI  - Cardiac amyloidosis: can advances in diagnostics and treatments improve survival?
AB  - Amyloidosis is a generalised clinical disorder characterised by extracellular
      deposition of amyloid fibrils. Symptomatic cardiac amyloidosis is typically
      associated with light chain (AL) amyloidosis in the western world. Amyloid
      deposition in the myocardium causes restrictive cardiomyopathy. Cardiac
      manifestations affect patient's performance status and limit therapeutic options.
      We present a case of rapidly progressing cardiac amyloid deposition due to AL
      amyloidosis presenting with typical features of restrictive cardiomyopathy. We
      also discuss the advances in non-invasive diagnostic techniques applied in this
      case and currently available novel treatments. Early diagnosis and better
      response to novel treatments could potentially improve the overall survival in
      this group of patients.

PMID- 21847419
TI  - Hemophagocytic lymphohistiocytosis-late diagnosis in an adult patient.
AB  - We present a case of hemophagocytic lymphohistiocytosis (HLH) in a previously
      healthy 30-year-old woman. The patient presented with features consistent with
      HLH: persistent fever, neurological abnormalities, lymphadenopathy, anaemia,
      leucopoenia and markedly elevated serum lactate dehydrogenase and ferritin
      levels. Diagnosis was delayed for approximately 1 month beyond presentation. Once
      initiated on treatment, the patient rapidly improved and was discharged from the
      intensive care unit and subsequently sent home. Unfortunately, she succumbed to
      progressive HLH 5 months after her initial presentation. This case highlights key
      clinical features associated with HLH to help prevent late diagnosis as delayed
      treatment may lead to irreversible multi-organ failure and/or death.

PMID- 21847420
TI  - Undiagnosed coarctation of the aorta as a cause of aortic dissection in the
      young.
AB  - A 35-year-old man presented to the Emergency Department with a history of severe
      acute central chest pain and simultaneous bilateral paralysis the legs with
      double incontinence. There was no significant past medical or family history. A
      CT scan showed a thoracic dissection of the aorta extending from the aortic root
      to the aortic bifurcation and in to the common iliac arteries. The patient was
      consented for an axillo-femoral bypass and was taken to theatre and operated on
      for 7 hours. The patient unfortunately died under anaesthesia. A hospital post
      mortem was requested to identify the cause of the dissection. The patient's heart
      was sent to a cardiac pathologist who identified an undiagnosed coarctation of
      the aorta. Genetic testing was negative for Marfan syndrome.As a result of the
      post-mortem, it was recommended that first degree relatives of the deceased
      undergo ultrasound examination of the cardiovascular system as appropriate to
      exclude coarctation of the aorta.

PMID- 21847421
TI  - Mirtazapine: a solution for postoperative gastroparesis?
AB  - This report describes the case of a 52-year-old man with an obstructed para
      oesophageal hiatus hernia who required a gastropexy, who postoperatively
      developed gastroparesis which inadequately responded to conventional prokinetics
      including erythromycin, metoclopramide, ondansetron, and domperidone. The
      patient's symptoms were relieved rapidly with a trial of mirtazapine. A review of
      related literature is presented.

PMID- 21847423
TI  - Post liver transplant tuberculosis.
AB  - We report on a patient diagnosed with disseminated (hepatic and pulmonary)
      tuberculosis in the context of immunosuppression following liver transplant.
      During the administration of anti-tuberculosis drugs an abrupt elevation of liver
      enzymes was detected leading us to suspect drug toxicity rather than graft
      rejection. Nevertheless, careful surveillance and adjustment of serum levels of
      immunosuppressant drugs permitted continuance of tuberculosis treatment with no
      further side effects.

PMID- 21847422
TI  - Pulmonary oedema and hyponatraemia after an ironman triathlon.
AB  - A 36-year-old man presented with symptoms of acute pulmonary oedema at the
      conclusion of the Australian ironman triathlon. He was alert, orientated, with an
      oxygen saturation of 75% on room air. Chest examination revealed bilateral basal
      crepitations. Serum sodium was 120 mmol/L and chest x ray revealed bilateral
      basal opacities. He was treated for acute pulmonary oedema with prompt
      improvement and given 200 ml of intravenous hypertonic saline followed by normal
      saline. Serum sodium decreased to 117 mmol/L and 30 hours after presentation he
      had a seizure. He fully recovered and was discharged 5 days after admission. This
      case highlights that exercise-associated hyponatraemia and pulmonary oedema are
      still not widely understood and there is still a reluctance to treat
      hyponatraemia aggressively with ongoing hypertonic saline.

PMID- 21847424
TI  - Delirium in a 74-year-old man: correct imaging revealed the truth.
AB  - Delirium is a cognitive disorder. DSM-IV criteria for delirium must include both
      acute onset and fluctuating symptoms; disturbance of consciousness (including
      inattention); at least one of the following: disorganised thinking,
      disorientation, memory impairment or perceptual disturbance; and evidence of a
      putative causal medical condition. Traditionally, the course has been described
      as transient in which recovery is likely to be complete if the underlying
      aetiological factor is promptly corrected or is self-limited. The most common
      precipitating causes in elderly include sepsis, dehydration and drugs. Work-up
      for delirium is limited to septic screening, baseline investigations and imaging.
      Patients with delirium without focal signs and with either evidence for a medical
      aetiology of delirium or pre-diagnosed dementia are at a very low risk of having
      focal lesions in their contrast-enhanced CT or MRI. We are presenting an
      interesting case of delirium with urosepsis whose imaging revealed milliary brain
      tuberculomas on contrast-enhanced MRI.

PMID- 21847425
TI  - Myocardial fibrosis in an veteran endurance athlete.
AB  - This study reports the cardiac structure and function of a lifelong male
      endurance athlete, who has run over 148 000 miles, who presented with symptoms of
      chest discomfort, dyspnoea and loss of competitive running performance.
      Importantly, the athlete documented several periods of regular intensive
      endurance activity while suffering with flu-like symptoms. Cardiovascular MRI
      demonstrated a pattern of late gadolinium enhancement, which indicated myocardial
      scarring as a result of previous myocarditis.Myocarditis is a non-ischaemic
      inflammatory disease of the myocardium associated with cardiac dysfunction and
      arrhythmogenic substrate. The clinical course of viral myocarditis is mostly
      insidious with limited cardiac inflammation and dysfunction. However, as in the
      present case, overwhelming inflammation may occur in a subset of patients leading
      to myocardial fibrosis due to recurrent inflammation.

PMID- 21847426
TI  - Rhabdomyolysis with erratic serum creatinin phosphokinase levels: intramuscular
      injection of haloperidol decanoate.
AB  - A 56-year-old African American female with a history of schizophrenia developed
      rhabdomyolysis with creatine phosphokinase (CPK) levels of 5172 U/L after
      intramuscular injection of haloperidol decanoate. The patient was admitted to the
      hospital and treated with saline infusion alone. Serum CPK levels were decreased
      but not significantly so even after 4 days. Renal function tests and vital signs
      remained normal throughout her stay in the hospital. Urinary alkalinisation was
      done with sodium bicarbonate to maintain urine pH higher than 6.5 and the CPK
      levels declined gradually over the next 3 days. The patient was observed for 24
      hours without saline infusion and urine alkalinisation but the serum CPK levels
      continued to increase and this regimen was restarted. The patient stayed in the
      hospital for 4 weeks on this regimen until the CPK levels decreased and remained
      normal. Our patient developed rhabdomyolysis without neuroleptic malignant
      syndrome.

PMID- 21847427
TI  - Thoughts upon assuming the role of Editor-in-Chief.

PMID- 21847428
TI  - Effect of massage on pain management for thoracic surgery patients.
AB  - BACKGROUND: Integrative therapies such as massage have gained support as
      interventions that improve the overall patient experience during hospitalization.
      Thoracic surgery patients undergo long procedures and commonly have postoperative
      back, neck, and shoulder pain. PURPOSE: Given the promising effects of massage
      therapy for alleviation of pain, we studied the effectiveness and feasibility of
      massage therapy delivered in the postoperative thoracic surgery setting. METHODS:
      Patients who received massage in the postoperative setting had pain scores
      evaluated pre and post massage on a rating scale of 0 to 10 (0 = no pain, 10 =
      worst possible pain). RESULTS: In total, 160 patients completed the pilot study
      and received massage therapy that was individualized. Patients receiving massage
      therapy had significantly decreased pain scores after massage (p <= .001), and
      patients' comments were very favorable. Patients and staff were highly satisfied
      with having massage therapy available, and no major barriers to implementing
      massage therapy were identified. CONCLUSIONS: Massage therapy may be an important
      additional pain management component of the healing experience for patients after
      thoracic surgery.

PMID- 21847429
TI  - Case study: a year in the life of a massage research curriculum.

PMID- 21847430
TI  - Letter to the editor.

PMID- 21847432
TI  - Nitric oxide as a putative retinal axon pathfinding and target recognition cue in
      Xenopus laevis.
AB  - Nitric oxide (NO) is an atypical neurotransmitter synthesized by the enzyme
      nitric oxide synthase (NOS) during many stages of the Xenopus laevis life cycle.
      This research investigates whether the gas NO is involved in axon guidance, the
      neurodevelopmental process in which axons travel through the brain to their
      appropriate target locations to form functional neural circuitry. Through
      immunocytochemistry and direct labeling of the NO gas with a fluorescent dye, we
      have found that NOS expression corresponds spatiotemporally with the beginning of
      retinal axon innervation of the optic tectum in X. laevis. Our function-blocking
      studies in which NO is chemically inhibited suggest that NO may be necessary for
      correct pathfinding and targeting, evidenced by qualitative widening of the optic
      tract and aberrant target innervation.

PMID- 21847433
TI  - Flap complications and thrombophilia: an evidence-based model and cost analysis
      for preoperative screening.
AB  - BACKGROUND: Preoperative screening for thrombophilias in free flap candidates may
      be cost-effective. METHODS: We developed a model for thrombogenic flap
      complications using reported thrombophilia prevalences and thromboembolic risk
      ratios, as well as free flap complication rates from our institution. We
      performed a break-even and incremental cost-effective ratio analysis for several
      screening and intervention scenarios. RESULTS: Our thrombotic free flap
      complication rate is 4.9%. A full thrombophilia screen breaks even when the cost
      of complication exceeds $57 000 per patient; a limited screen breaks even at $39
      000, and a scenario in which all patients undergo chemoprophylaxis breaks even at
      $49 000. Incremental cost-effective ratio analyses estimate a cost per avoided
      flap complication of $33 638 for a full panel scenario, $15 617 for a limited
      panel scenario and $25 455 for an all therapy scenario. CONCLUSIONS: Our analyses
      show that preoperative thrombophilia screening may be a cost-effective measure
      for the prevention of free flap thrombotic complications.

PMID- 21847435
TI  - Topics in otoplasty: ear deformity and auricular constriction.

PMID- 21847434
TI  - Electrical stimulation in bone healing: critical analysis by evaluating levels of
      evidence.
AB  - OBJECTIVES: Direct current, capacitive coupling, and inductive coupling are modes
      of electrical stimulation (ES) used to enhance bone healing. It is important to
      assess the effectiveness of ES for bone healing to ensure optimization for
      clinical practice. This review aims to examine the level of evidence (LOE) for
      the application of ES to enhance bone healing and investigate the proposed
      mechanism for its stimulatory effect. METHODS: MEDLINE and EMBASE searches were
      conducted to identify clinical and in vitro studies utilizing ES for bone healing
      since 1959. A total of 105 clinical studies and 35 in vitro studies were
      evaluated. Clinical studies were assigned LOE according to Oxford Centre for
      Evidence Based Medicine (LOE-1, highest; LOE-5, lowest). RESULTS: Direct current
      was found to be effective in enhancing bone healing in spinal fusion but only LOE
      4 supported its use for nonunions. Eleven studies were retrieved for capacitive
      coupling with LOE-1 demonstrating its effectiveness for treating nonunions. The
      majority of studies utilized inductive coupling with LOE-1 supporting its
      application for healing osteotomies and nonunions. In vitro studies demonstrate
      that ES enhances bone healing by changes in growth factors and transmembrane
      signaling although no clear mechanism has been defined. CONCLUSION: Overall, the
      studies, although in favor of ES application in bone repair, displayed
      variability in treatment regime, primary outcome measures, follow-up times, and
      study design, making critical evaluation and assessment difficult. Electrical
      stimulation shows promise in enhancement of bone healing; however, better
      designed clinical studies will enable the optimization for clinical practice.

PMID- 21847436
TI  - A spontaneous adult right-sided Bochdalek hernia containing perforated colon.

PMID- 21847437
TI  - Prevalences of overweight, obesity, hyperglycaemia, hypertension and
      dyslipidaemia in the Gulf: systematic review.
AB  - OBJECTIVES: To examine the prevalence of risk factors for diabetes and its
      complications in the Co-operation Council of the Arab States of the Gulf (GCC)
      region. DESIGN: Systematic review. SETTING: Co-operation Council of the Arab
      States of the Gulf (GCC) states (United Arab Emirates, Bahrain, Saudi Arabia,
      Oman, Qatar, Kuwait). PARTICIPANTS: Residents of the GCC states participating in
      studies on the prevalence of overweight and obesity, hyperglycaemia, hypertension
      and dyslipidaemia. MAIN OUTCOME MEASURES: Prevalences of overweight, obesity and
      hyperglycaemia, hypertension and hyperlipidaemia. RESULTS: Forty-five studies
      were included in the review. Reported prevalences of overweight and obesity in
      adults were 25-50% and 13-50%, respectively. Prevalence appeared higher in women
      and to hold a non-linear association with age. Current prevalence of impaired
      glucose tolerance was estimated to be 10-20%. Prevalence appears to have been
      increasing in recent years. Estimated prevalences of hypertension and
      dyslipidaemia were few and used varied definitions of abnormality, making review
      difficult, but these also appeared to be high and increasing, CONCLUSIONS: There
      are high prevalences of risk factors for diabetes and diabetic complications in
      the GCC region, indicative that their current management is suboptimal. Enhanced
      management will be critical if escalation of diabetes-related problems is to be
      averted as industrialization, urbanization and changing population demographics
      continue.

PMID- 21847438
TI  - Use of the NHS Choices website for primary care consultations: results from
      online and general practice surveys.
AB  - OBJECTIVES: To determine the effect of using the NHS Choices website on primary
      care consultations in England and Wales. We examined the hypothesis that using
      NHS Choices may reduce the frequency of primary care consultations among young,
      healthy users. DESIGN: Two cross-sectional surveys of NHS Choices users. SETTING:
      Survey of NHS Choices users using an online pop-up questionnaire on the NHS
      Choices website and a snapshot survey of patients in six general practices in
      London. PARTICIPANTS: NHS Choices website users and general practice patients.
      MAIN OUTCOME MEASURES: For both surveys, we measured the proportion of people
      using NHS Choices when considering whether to consult their GP practice and on
      subsequent frequency of primary care consultations. RESULTS: Around 59% (n =
      1559) of online and 8% (n = 125) of general practice survey respondents reported
      using NHS Choices in relation to their use of primary care services. Among these,
      33% (n = 515) of online and 18% (n = 23) of general practice respondents reported
      reduced primary care consultations as a result of using NHS Choices. We estimated
      the equivalent capacity savings in primary care from reduced consultations as a
      result of using NHS Choices to be approximately L94 million per year.
      CONCLUSIONS: NHS Choices has been shown to alter healthcare-seeking behaviour,
      attitudes and knowledge among its users. Using NHS Choices results in reduced
      demand for primary care consultations among young, healthy users for whom reduced
      health service use is likely to be appropriate. Reducing potentially avoidable
      consultations can result in considerable capacity savings in UK primary care.

PMID- 21847439
TI  - Renal colic in a dialysis patient: a case of renal stone disease.

PMID- 21847440
TI  - Precipitation of thiopental with muscle relaxants: a potential hazard.

PMID- 21847441
TI  - Diagnostic accuracy of white cell count and C-reactive protein for assessing the
      severity of paediatric appendicitis.
AB  - OBJECTIVES: Simple investigations like white cell count (WCC) and C-reactive
      protein (CRP) may help to improve the accuracy of diagnosis in paediatric
      appendicitis. We evaluated the diagnostic accuracy of WCC and CRP for the
      severity of acute appendicitis in children. DESIGN: Cross-sectional study.
      SETTING: This study was conducted on all children who underwent open appendectomy
      from January 2007 to December 2008 at a District General Hospital. Data regarding
      demographics, WCC, CRP, histology and postoperative complications were analysed.
      PARTICIPANTS: All children who underwent open appendectomy during the study
      period. MAIN OUTCOME MEASURES: Diagnostic accuracy of WCC and CRP for simple
      acute appendicitis and a perforated appendix. RESULTS: Out of 204 patients, 112
      (54.9%) were girls. At surgery, appendix was grossly inflamed in 175 of which 32
      had perforation. Histology revealed simple acute appendicitis in 135 (66.2%) and
      gangrenous appendicitis in 32 (15.7%). The rest were normal. The duration of
      symptoms, temperature, length of stay, WCC and CRP were significantly worse in
      the perforated group (P value <0.05). Postoperative complications included wound
      infection (n = 18), pelvic collection (n = 5) and intestinal obstruction (n = 6);
      and were more common among patients with a perforated appendix (P value <0.05).
      WCC had a higher diagnostic accuracy and higher sensitivity than CRP in
      diagnosing simple acute appendicitis. The combined sensitivity of WCC and CRP
      increased to 95% and 100% for the diagnosis of simple acute appendicitis and a
      perforated appendix, respectively. CONCLUSION: Accuracy of WCC is higher than CRP
      for diagnosing simple acute appendicitis. The combined sensitivity of WCC and CRP
      increases for simple acute appendicitis as well as a perforated appendix.

PMID- 21847442
TI  - Comparing the USA, UK and 17 Western countries' efficiency and effectiveness in
      reducing mortality.
AB  - OBJECTIVES: To test the hypothesis that the USA healthcare system was superior to
      the NHS and 17 other Western countries in reducing feasible mortality rates over
      the period 1979-2005. DESIGN: Economic inputs into healthcare, GDP health
      expenditure (GDPHE) were compared with clinical outputs, i.e. total 'adult' (15
      74 years) and 'older' (55-74 years) mortality rates based upon three-year average
      mortality rates for 1979-81 vs. 2003-2005. A cost-effective ratio was calculated
      by dividing average GDPHE into reduced mortality rates over the period. SETTING:
      Nineteen Western countries' mortality rates compared between 1979-2005.
      PARTICIPANTS: Mortality of people by age and gender. MAIN OUTCOME MEASURES: A
      cost-effective ratio to measure efficiency and effectiveness of healthcare
      systems in reducing mortality rates. Chi-square tested any differences between
      the USA, UK and other Western countries. RESULTS:  INPUT: The USA had the highest
      current and average GDPHE; the UK was 10th highest but joint 16th overall, still
      below the Western countries' average. Output: Every country's mortality rate fell
      substantially; but 15 countries reduced their mortality rates significantly more
      than the US, while UK 'adult' and 'older' mortality rates fell significantly more
      than 12 other countries. Cost-effectiveness: The USA GDPHE: mortality rate ratio
      was 1:205 for 'adults' and 1:515 for 'older' people, 16 Western countries having
      bigger ratios than the US; the UK had second greatest ratios at 1:593 and 1:1595,
      respectively. The UK ratios were >20% larger than 14 other countries.
      CONCLUSIONS: In cost-effective terms, i.e. economic input versus clinical output,
      the USA healthcare system was one of the least cost-effective in reducing
      mortality rates whereas the UK was one of the most cost-effective over the
      period.

PMID- 21847443
TI  - A rare but important cause of fulminant hepatic failure.

PMID- 21847444
TI  - Congenital epulis of the tongue: A case report and review of the literature.

PMID- 21847445
TI  - Optimizing secondary prevention: Statin prescribing across East and West London
      in accordance with NICE guidelines.
AB  - OBJECTIVES: Statins are a well-known primary and secondary prevention drug for
      cardiovascular disease and NICE guidelines have been issued to identify key
      indicators for their use. An audit looking into statin prescribing for medical
      inpatients was carried out in two geographically distinct London hospitals.
      DESIGN: A prospective inpatient audit of medical prescription charts was
      performed. Blood results were reviewed for the inpatients during their admission
      to identify any contraindications for statin usage (rhabdomyolysis). The medical
      notes were also reviewed for patient refusal of statin therapy. SETTING: The
      study was carried out at two distinct hospitals in London. Whipps Cross
      University Hospital (WCUH) and Chelsea & Westminster Hospital (CWH) are located
      in East London and West London, respectively. Acute medical, surgical, obstetrics
      and gynaecology, paediatric and palliative wards were excluded. PARTICIPANTS: A
      total of 309 inpatient medical notes and prescription chart data were collected
      from WCUH (n = 211) and CWH (n = 98). MAIN OUTCOME MEASURES: High percentage of
      hospitalized patients are not prescribed statins despite clear clinical
      indications for their use. Regardless of geographical and socioeconomic factors
      between hospitals, statin prescribing remains suboptimal. RESULTS: The patient
      demographics in both hospitals were very similar; the mean age at WCUH was 78 +/-
      15 1SD while at CWH the mean age was 74 +/- 15 1SD. The results showed that
      approximately one-third of patients (30% at WCUH and 33% at CWH) had at least one
      indication for statin therapy according to NICE guidelines and yet they were not
      prescribed a statin. Ten percent of patients at WCUH and 13% of patients at CWH
      had ischaemic heart disease (IHD) and yet were not prescribed statins.
      CONCLUSION: Statin prescription is often overlooked in secondary care with
      patients being discharged without the appropriate assessment (NICE guidelines),
      which subsequently means repeat prescriptions are not provided by the GP. This
      study is the first to show that this problem is not due to resources or
      geography, but is inherent within the NHS system. Consequently, a revised
      prescription chart checking system has been suggested for pharmacists and junior
      doctors.

PMID- 21847446
TI  - Incidence and Remission of Parasomnias among Adolescent Children in the Tucson
      Children's Assessment of Sleep Apnea (TuCASA) Study.
AB  - BACKGROUND: Longitudinal assessments of parasomnias in the adolescent population
      are scarce. This analysis aims to identify the incidence and remission of
      parasomnias in the adolescent age group.  METHODS: The TuCASA study is a
      prospective cohort study that initially enrolled children between the ages of 6
      and 11 years (Time 1) and subsequently restudied them approximately 5 years later
      (Time 2). At both time points parents were asked to complete a comprehensive
      sleep habits questionnaire designed to assess the severity of sleep-related
      symptoms that included questions about enuresis (EN), sleep terrors (TR), sleep
      walking (SW) and sleep talking (ST).  RESULTS: There were 350 children
      participating at Time 1 who were studied as adolescents at time 2. The mean
      interval between measurements was (4.6 years). The incidence of EN, TR, ST, and
      SW in these 10-18 year old children was 0.3%, 0.6%, 6.0% and 1.1% respectively.
      Remission rates were 70.8%, 100%, 64.8% and 50.0% respectively.  CONCLUSIONS: The
      incidence rates of EN, TR, and SW were relatively low moving from childhood to
      adolescence while remission rates were high across all parasomnias.

PMID- 21847447
TI  - Adrenergic India: Managing its diabetes.

PMID- 21847448
TI  - Degludec insulin: A novel basal insulin.
AB  - This paper reviews a novel insulin analogue, degludec, which has the potential to
      emerge as an ideal basal insulin. It reviews the limitations of existing basal
      insulin and analogues, and highlights the need for a newer molecule. The paper
      discusses the potential advantages of degludec, while reviewing its pharmacologic
      and clinical studies done so far. The paper assesses the potential role of
      insulin degludec and degludec plus in clinical diabetes practice.

PMID- 21847449
TI  - Bromocriptine in type 2 diabetes mellitus.
AB  - Bromocriptine mesylate quick-release was approved by the Food and Drug
      Administration (FDA) in May 2009, for the treatment of type 2 diabetes.
      Bromocriptine is thought to act on the circadian neuronal activities in the
      hypothalamus, to reset an abnormally elevated hypothalamic drive for increased
      plasma glucose, free fatty acids, and triglycerides in insulin-resistant
      patients. Randomized controlled trials have shown that bromocriptine-QR lowers
      glycated hemoglobin by 0.4 - 0.8% either as monotherapy or in combination with
      other anti-diabetes medications. The doses used to treat diabetes (up to 4.8 mg
      daily) are much lower than those used to treat Parkinson's disease, and apart
      from nausea, the drug is well-tolerated. The novel mechanism of action, good side
      effect profile, and its effects to reduce cardiovascular event rates make it an
      attractive option for the treatment of type 2 diabetes.

PMID- 21847450
TI  - Imaging of the pancreas: Recent advances.
AB  - A wide spectrum of anomalies of pancreas and the pancreatic duct system are
      commonly encountered at radiological evaluation. Diagnosing pancreatic lesions
      generally requires a multimodality approach. This review highlights the new
      advances in pancreatic imaging and their applications in the diagnosis and
      management of pancreatic pathologies. The mainstay techniques include computed
      tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS),
      radionuclide imaging (RNI) and optical coherence tomography (OCT).

PMID- 21847451
TI  - Every rose has it's thorn!

PMID- 21847452
TI  - Evaluation of the efficacy and safety of bromocriptine QR in type 2 diabetes.
AB  - CONTEXT: Diabetes mellitus is a chronic metabolic disorder of endocrinal origin
      with multiorgan involement. Today's physician has a lot many options to choose
      for treating type 2 diabetes, but does not always manages to achieve optimal
      glycemic control. The newer drug bromocriptine acts by novel hypothalamic
      circadian rhythm resetting mechanism. OBJECTIVE: To evaluate the efficacy and
      safety of bromocriptine QR in type 2 diabetes. MATERIALS AND METHODS: 105
      patients according to inclusion and exclusion criteria were randomized into three
      groups by simple randomization. Group 1 received bromocriprine 2.4 mg once daily,
      group 2 received metformin 500 mg twice daily while group 3 received
      bromocriprine 1.6 mg daily and metformin 500 mg twice daily. Baseline measurement
      of fasting and postprandial blood sugar, HbA1(C) and BMI were followed up at
      6(th) and 12(th) weeks. Safety evaluation was done by questioning the patient and
      also through routine hematological and biochemical parameters. Z test was used
      for analysis. RESULTS: Group 1 showed significant reduction in fasting and
      postprandial sugar and HbA(1c) at 12 weeks. While groups 2 and 3 showed even
      higher reduction in these parameters albeit with slightly more adverse drug
      events like nausea, vomiting compared to group 1. CONCLUSION: Bromocriptine QR is
      an effective and safe antidiabetic drug which can be employed as monotherapy or
      in conjuction with metformin to achieve and maintain optimal glycemic control.

PMID- 21847453
TI  - Clinical and biochemical profile of lean type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus is the most prevalent form of diabetes
      worldwide. In western countries majority of the cases are obese. The scenario may
      be different in certain parts of India. Various studies have reported a high
      prevalence of lean type 2 diabetes mellitus with a body mass index < 19 kg/m(2).
      MATERIALS AND METHODS: We evaluated 100 cases of lean type 2 diabetes mellitus
      (62 males and 38 females). RESULTS AND CONCLUSION: The mean duration of diabetes
      was 51.7 months (range 5-180 months). The glycemic control was poor according to
      standard guidelines. The majority of them showed response to oral hypoglycemic
      agents. Secondary failure to oral hypoglycemic agents was seen in 27 patients.
      The prevalence of microvascular complications was much higher than macrovascular
      complications. Neuropathy was the commonest complication seen in 70%, followed by
      retinopathy in 25%. Only 12 patients had hypertension, one had coronary artery
      disease and two had cerebrovascular accident. Lipid profile was not significantly
      deranged in our patients.

PMID- 21847454
TI  - Study of beta-cell function (by HOMA model) in metabolic syndrome.
AB  - INTRODUCTION: The clustering of cardiovascular risk factors is termed the
      metabolic syndrome (MS), which strongly predict risk of diabetes and
      cardiovascular disease. Many studies implicate insulin resistance (IR) in the
      development of diabetes, but ignore the contribution of beta-cell dysfunction.
      Hence, we studied beta-cell function, as assessed by HOMA model, in subjects with
      MS. MATERIALS AND METHODS: We studied 50 subjects with MS diagnosed by IDF
      criteria and 24 healthy age- and sex-matched controls. Clinical evaluation
      included anthropometry, body fat analysis by bioimpedance, biochemical, and
      insulin measurement. IR and secretion were calculated by HOMA model. RESULTS:
      Subjects with MS had more IR (HOMA-IR) than controls (3.35 +/- 3.14 vs. 1.76 +/-
      0.53, P = 0.029) and secreted less insulin (HOMA-S) than controls (66.80 +/-
      69.66 vs. 144.27 +/- 101.61, P = 0.0003), although plasma insulin levels were
      comparable in both groups (10.7 +/- 10.2 vs. 8.2 +/- 2.38, P = 0.44). HOMA-IR and
      HOMA-S were related with number of metabolic abnormalities. HOMA-IR was
      positively associated with body mass index, waist hip ratio, body fat mass, and
      percent body fat. HOMA-S was negatively associated with waist hip ratio, fasting
      plasma glucose and total cholesterol and positively with basal metabolic rate.
      Percent body fat was an independent predictor of HOMA-IR and waist hip ratio of
      HOMA-S in multiple regression analysis. CONCLUSIONS: Subjects with MS have
      increased IR and decreased insulin secretion compared with healthy controls.
      Lifestyle measures have been shown to improve IR, insulin secretion, and various
      components and effects of MS. Hence, there is an urgent need for public health
      measures to prevent ongoing epidemic of diabetes and cardiovascular disease.

PMID- 21847455
TI  - Noninsulin pharmacological management of type 1 diabetes mellitus.
AB  - The injectable nature and other shortcomings of insulin have stimulated interest
      in studying the noninsulin pharmacological therapies to manage type 1 diabetes
      mellitus (T1DM). The purpose of this study is to conduct a systematic literature
      review of noninsulin pharmacological therapies for the management of T1DM. For
      this, the following PubMed search was conducted: Diabetes Mellitus, Type
      1/therapy"[Mesh] LIMITS: Review Sort by: Publication Date. After applying various
      inclusion and exclusion criteria, a total of 63 studies were reviewed. Based on
      this review, noninsulin pharmacological therapies can be divided into following
      classes: (1) Insulin-sensitizing agents (biguanides and thiazolidinediones), (2)
      gastrointestinal nutrient absorption modulators (alpha-Glucosidase inhibitors and
      amylin), (3) immunotherapeutic agents, (4) incretin-based therapies, (5)
      recombinant human insulin-like growth factors, and (6) other promising
      therapeutics. Some of these are already used either as monotherapy or adjuvant to
      insulin, whereas, to manage T1DM, the benefits and risks of the others are still
      under evaluation. Nonetheless, insulin still remains the cornerstone to manage
      the T1DM.

PMID- 21847457
TI  - Emphysematous cystitis in a patient with type-2 diabetes mellitus.
AB  - Emphysematous cystitis is a relatively rare clinical entity caused by gas
      fermenting bacteria or fungus. Presentation is often nonspecific and imaging is
      the best diagnostic modality. We report a case of a 45-year-old male who
      presented with fever, dysuria, and pneumaturia, and was found to have
      emphysematous cystitis.

PMID- 21847456
TI  - Correlates of anxiety and depression among patients with type 2 diabetes
      mellitus.
AB  - CONTEXT: Research has established the relation between diabetes and depression.
      Both diabetes and anxiety/depression are independently associated with increased
      morbidity and mortality. AIMS: The present study aims at assessing the prevalence
      of anxiety/depression among outpatients receiving treatment for type 2 diabetes.
      SETTINGS AND DESIGN: The study was conducted in the endocrinology outpatient
      department of an urban tertiary care center. MATERIALS AND METHODS: The
      instruments used included a semi-structured questionnaire, HbA1c levels, fasting
      blood glucose and postprandial blood glucose, Brief Patient Health Questionnaire,
      and Hospital Anxiety and Depression Scale (HADS). STATISTICAL ANALYSIS USED:
      Analysis was carried out using the SPSS version 16.0. Pearson's correlation
      coefficient was calculated to find out the correlations. ANOVA was carried out
      for the in between group comparisons. RESULTS: There was a significant
      correlation between the HADS-Anxiety scale and Body Mass Index (BMI) with a
      correlation coefficient of 0.34 (P = 0.008). Also, a significant correlation
      existed between HADS-Depression scale and BMI (correlation coefficient, 0.36; P =
      0.004). Significant correlation were observed between the duration of daily
      physical exercise and HADS-Anxiety (coefficient of correlation, -0.25; P = 0.04)
      scores. HADS-Anxiety scores were found to be related to HbA1c levels (correlation
      coefficient, 0.41; P = 0.03) and postprandial blood glucose levels (correlation
      coefficient, 0.51; P = 0.02). CONCLUSIONS: Monitoring of biochemical parameters
      like HbA1c and postprandial blood glucose levels and BMI could be a guide to
      development of anxiety in these patients. Also, physical exercise seems to have a
      protective effect on anxiety in those with type 2 diabetes mellitus.

PMID- 21847458
TI  - Diabetic myonecrosis: An underreported complication of diabetes mellitus.
AB  - Diabetic myonecrosis is an underreported complication of long-standing, poorly
      controlled diabetes mellitus which is usually self-limiting and responds well to
      conservative management. Patients frequently have microvascular complications,
      and although short-term prognosis is good, the long-term prognosis is poor. We
      report four cases of diabetic myonecrosis admitted in a tertiary care hospital.

PMID- 21847459
TI  - Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in
      an infant.
AB  - Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder
      characterized by severe generalized lipodystrophy, insulin resistance, and
      dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence.
      Here we report a 5-month-old infant with clinical and metabolic manifestations of
      Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which
      are very rare at this age.

PMID- 21847460
TI  - Rhino-orbital-mucormycosis as a presenting manifestation of gestational diabetes
      mellitus.
AB  - Rhino-orbital mucormycosis is an uncommon and aggressive, angioinvasive fungal
      infection that occurs in immunocompromised states like diabetes mellitus, chronic
      renal failure, hematological malignancies and deferroxamine therapy. We report a
      patient who presented with rhino-orbital mucormycosis at six months of gestation
      and was incidentally detected to have diabetes. She was successfully treated with
      amphotericin B and appropriate surgery. To the best of our knowledge, there is no
      such report in the literature.

PMID- 21847461
TI  - Diabetic cardiac autonomic neuropathy in well-controlled diabetics within 1 year
      of diagnosis.

PMID- 21847462
TI  - Asymptomatic peripheral artery disease in South Indian women with type 2
      diabetis.

PMID- 21847463
TI  - Health economic evaluation of dipeptidyl peptidase-4 inhibitors.

PMID- 21847464
TI  - Outbreak of Escherichia coli and diabetes mellitus.

PMID- 21847466
TI  - Enhanced rate performance and cyclic stability of Fe3O4-graphene nanocomposites
      for Li ion battery anodes.
AB  - Monodispersed Fe(3)O(4) nanoparticles of size ~10 nm were processed by a simple
      ultrasonic assisted co-precipitation method, mechanically mixed with graphene
      oxide, and thermally reduced to form a magnetite-graphene composite.
      Electrochemical characterization of the Fe(3)O(4)-graphene nanocomposites showed
      excellent capacity in excess of 1200 mA h g(-1), and exceptional stability during
      high current cycling for at least 1000 cycles.

PMID- 21847467
TI  - Enhanced anode performances of the Fe3O4-carbon-rGO three dimensional composite
      in lithium ion batteries.
AB  - A three dimensional composite was constructed by anchoring Fe(3)O(4)
      nanoparticles encapsulated within carbon shells onto reduced graphene oxide
      sheets, which exhibited enhanced anode performances in lithium ion batteries with
      a specific capacity of 842.7 mAh g(-1) and superior recycle stability after 100
      cycles.

PMID- 21847468
TI  - Transformation of ionic liquid into carbon nanotubes in confined nanospace.
AB  - We have developed a two-step filling process for the nano-reaction of ionic
      liquid in a tip-closed SWNT, where fullerenes are inserted at the end of the host
      SWNT as a plug to prevent the leakage of the confined ionic liquid during heat
      treatment.

PMID- 21847469
TI  - Correlation effects on the structure and dynamics of the H3O+ hydrate: B3LYP/MM
      and MP2/MM MD simulations.
AB  - Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics
      (MD) simulations, namely B3LYP/MM and MP2/MM, have been performed to investigate
      the possible influence of electron correlation on the structure and dynamics of
      the H(3)O(+) hydrate. In comparison to the previously published HF/MM results,
      both B3LYP/MM and MP2/MM simulations clearly reveal stronger H(3)O(+)-water
      hydrogen bond interactions, which are reflected in a slightly greater compactness
      of the H(3)O(+) hydrate. However, the B3LYP/MM simulation, although providing
      structural details very close to the MP2/MM data, shows an artificially slow
      dynamic nature of some first shell water molecules as a consequence of the
      formation of a long-lived H(3)O(+)...H(2)O hydrogen bonding structure.

PMID- 21847470
TI  - Influence of water on the formation of O2-reactive divalent metal enolate
      complexes of relevance to acireductone dioxygenases.
AB  - Reaction conditions were evaluated for the preparation of [(6
      PhTPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO(4) (3) and [(6
      Ph(2)TPA)Co(PhC(O)C(OH)C(O)Ph)]ClO(4) (7), two complexes of structural relevance
      to the enzyme/substrate (ES) adduct in Ni(II)- and Co(II)-containing forms of
      acireductone dioxygenase. The presence of water in reactions directed at the
      preparation of 3 and 7 was found to result in isomerization of the enolate
      precursor 2-hydroxy-1,3-diphenylpropane-1,3-dione to give the ester 2-oxo-2
      phenylethylbenzoate. Performing synthetic procedures under dryer conditions
      reduced the amount of ester production and enabled the isolation of 3 in high
      yield. This complex was comprehensively characterized, including by X-ray
      crystallography. Using similar conditions for the 6-Ph(2)TPACo-containing system,
      the amount of ester generated was only modestly affected, but the formation of a
      benzoate complex ([(6-Ph(2)TPA)Co(O(2)CPh)]ClO(4), 10) resulting from ester
      hydrolysis was prevented. The best preparation of 7 was found to involve dry
      conditions and short reaction times. The approach outlined herein toward
      determining appropriate reaction conditions for the preparation of 3 and 7
      involved the preparation and characterization of several air-stable (6-PhTPA)Ni-
      and (6-Ph(2)TPA)Co-containing analog complexes having enolate, solvent, and
      benzoate ligands. These complexes were used as paramagnetic (1)H NMR standards
      for evaluation of reaction mixtures containing 3 and 7.

PMID- 21847471
TI  - Indenyl ring slippage in crown thioether complexes [IndMo(CO)2L]+ and C-S
      activation of trithiacyclononane: experimental and theoretical studies.
AB  - The macrocycle 1,4,7-trithiacyclononane (ttcn) reacts with [(eta(5)
      Ind)Mo(CO)(2)(NCMe)(2)](+) (or [(eta(5)-Ind)Mo(CO)(2)(kappa(2)-dme)](+)) to give
      [(eta(3)-Ind)Mo(CO)(2)(kappa(3)-ttcn)](+) as the BF(4)(-) salt (1), but its
      reaction with [(eta(5)-Ind)Mo(CO)(2)(C(3)H(6))(FBF(3))] affords the C-S bond
      cleavage product [(eta(5)-Ind)Mo(CO)(kappa(3)-1,4,7-trithiaheptanate)]BF(4) (6),
      which has been characterised by X-ray crystallography (Ind = C(9)H(7), indenyl).
      In contrast to ttcn, the macrocycles 1,3,5-trithiane (tt) and 1,4,7,10
      tetrathiacyclododecane (ttcd) fail to induce changes in the coordination mode of
      indenyl: tt and ttcd react with [(eta(5)-Ind)Mo(CO)(2)(NCMe)(2)](+) (or [(eta(5)
      Ind)Mo(CO)(2)(kappa(2)-dme)](+)) to give [(eta(5)-Ind)Mo(CO)(2)(kappa(2)-tt)](+)
      (2), characterised by X-ray crystallography, and [(eta(5)-Ind)Mo(CO)(2)(kappa(2)
      ttcd)](+) (3), respectively. The cyclopentadienyl (Cp = C(5)H(5)) analogues
      [(eta(5)-CpMo(CO)(2)(kappa(2)-tt)](+) (4) and [(eta(5)-CpMo(CO)(2)(kappa(2)
      ttcn)](+) (5) have also been synthesised and 5 characterised by X-ray
      crystallography. DFT calculations showed that the eta(5)-Ind/Cp coordination mode
      is always the most stable. However, a molecular dynamics study of the macrocycles
      conformations revealed that the major conformer of ttcn was a chair, which
      favoured kappa(3) coordination. As indenyl complexes undergo slippage with a
      small barrier (<10 kcal mol(-1)), the kinetically preferred species [(eta(3)
      Ind)Mo(CO)(2)(kappa(3)-ttcn)](+) (1) is the observed one. The conversion to 6
      proceeds stepwise, with loss of ethylene followed by loss of CO, as calculated by
      DFT, with a barrier of 38.7 kcal mol(-1), consistent with the slow uncatalysed
      reaction.

PMID- 21847472
TI  - Enhanced Raman scattering and photocatalytic activity of Ag/ZnO heterojunction
      nanocrystals.
AB  - In this work, we study the enhancement of Raman signals and photocatalytic
      activity of Ag/ZnO heterojunctions with an Ag content of 1 at.%, which were
      synthesized by photochemical deposition of Ag nanoparticles onto pre-synthesized
      ZnO nanorods. A strong interaction between Ag and ZnO nanocrystals were evidenced
      by XPS and UV-vis spectroscopy. The binding energy of Ag nanoparticles shifts
      toward lower energy compared to that of pure Ag nanoparticles, revealing that
      electrons transfer from Ag to the ZnO nanocrystals. The red shift of the plasmon
      absorption peak of Ag nanoparticles in Ag/ZnO heterojunctions further confirms
      the strong interaction between the two components. This strong interaction,
      arising from the coupling between Ag and ZnO nanocrystals, is responsible for the
      enhancement of Raman signals and photocatalytic activity of the Ag/ZnO
      heterojunctions.

PMID- 21847473
TI  - Pharmaceutical formulation affects titanocene transferrin interactions.
AB  - Since the discovery of the anticancer activity of titanocene dichloride (TDC),
      many derivatives have been developed and evaluated. MKT4, a soluble, water-stable
      formulation of TDC, was used for both Phase I and Phase II human clinical trials.
      This formulation is investigated here by using (1)H and (13)C NMR, FT-ICR mass
      spectrometry, and UV/vis-detected pH-dependent speciation. DFT calculations are
      also utilized to assess the likelihood of proposed species. Human serum
      transferrin has been identified as a potential vehicle for the Ti anticancer
      drugs; these studies examine whether and how formulation of TDC as MKT4 may
      influence its interactions, both thermodynamic and kinetic, with human serum
      transferrin by using UV/vis absorption and fluorescence quenching. MKT4 binds
      differently than TDC to transferrin, showing different kinetics of binding as
      well as a different molar absorptivity of binding (7500 M(-1) cm(-1) per site).
      Malate, used in the buffer for MKT4 administration, acts as a synergistic anion
      for Ti binding, shifting the tyrosine to Ti charge transfer energy and decreasing
      the molar absorptivity to 5000 M(-1) cm(-1) per site. These differences may have
      had consequences after the change from TDC to MKT4 in human clinical trials.

PMID- 21847474
TI  - Haptotropic rearrangement in tricarbonylchromium complexes of 2-aminobiphenyl and
      4-aminobiphenyl.
AB  - The para-aminobiphenyl compound [(eta(6)-C(6)H(5))(C(6)H(4)-4-NH(2))]Cr(CO)(3)
      (1) has an arene-phenyl dihedral angle of 38.01(6) degrees , as determined by
      single-crystal X-ray crystallography, and 34.7(11) degrees , as determined by DFT
      calculations. It undergoes haptotropic rearrangement at 140  degrees C in
      solution to form [(eta(6)-C(6)H(4)-4-NH(2))(C(6)H(5))]Cr(CO)(3) (2), even though
      previous reports have suggested that such rearrangements should not be observed
      in compounds with arene-phenyl dihedral angles greater than 22 degrees . NMR
      analysis gave a rate constant of k = 5.0 * 10(-5) s(-1) for the rearrangement of
      1 to 2. The ortho-substituted analog [(eta(6)-C(6)H(5))(C(6)H(4)-2
      NH(2))]Cr(CO)(3) (3) has an arene-phenyl dihedral angle of 67.70(7) degrees , as
      determined by single-crystal X-ray crystallography, and 51.9(10) degrees , as
      determined by DFT calculations. Surprisingly, even though it displays a more
      extreme canting of arene rings, 3 rearranges to [(eta(6)-C(6)H(4)-2
      NH(2))(C(6)H(5))]Cr(CO)(3) (4) at 140  degrees C in solution with a rate constant
      of k = 2.6 * 10(-4) s(-1). This approximately five-fold rate enhancement likely
      results from the ortho-amino group providing intramolecular stabilization for
      intermediates formed during the rearrangement.

PMID- 21847475
TI  - Treating highly charged carbon and fullerene clusters as dielectric particles.
AB  - A model, recently developed for treating interactions between charged particles
      of dielectric materials (Bichoutskaia et al., J. Chem. Phys., 2010, 133, 024105),
      has been applied in an analysis of experimental data on the stability and
      fragmentation of highly charged carbon and fullerene clusters. Fragmentation data
      take the form of kinetic energy measurements that accompany the Coulomb fission
      of highly charged carbon clusters. For many of the examples chosen there is good
      agreement between the calculated and experimental results; however, the degree of
      uncertainty in some of the experimental data means that subtle features predicted
      by the model cannot be verified. When compared with an image charge model,
      treating carbon particles as a dielectric material reveals significant
      differences in the nature of the interaction potential.

PMID- 21847480
TI  - Targeting of anionic membrane species by lanthanide(III) complexes: towards
      improved MRI contrast agents for apoptosis.

PMID- 21847481
TI  - Proton transfer events in GFP.
AB  - Proton transfer is one of the most important elementary processes in biology.
      Green fluorescent protein (GFP) serves as an important model system to elucidate
      the mechanistic details of this reaction, because in GFP proton transfer can be
      induced by light absorption. Illumination initiates proton transfer through a
      'proton-wire', formed by the chromophore (the proton donor), water molecule W22,
      Ser205 and Glu222 (the acceptor), on a picosecond time scale. To obtain a more
      refined view of this process, we have used a combined approach of time resolved
      mid-infrared spectroscopy and visible pump-dump-probe spectroscopy to resolve
      with atomic resolution how and how fast protons move through this wire. Our
      results indicate that absorption of light by GFP induces in 3 ps (10 ps in D(2)O)
      a shift of the equilibrium positions of all protons in the H-bonded network,
      leading to a partial protonation of Glu222 and to a so-called low barrier
      hydrogen bond (LBHB) for the chromophore's proton, giving rise to dual emission
      at 475 and 508 nm. This state is followed by a repositioning of the protons on
      the wire in 10 ps (80 ps in D(2)O), ultimately forming the fully deprotonated
      chromophore and protonated Glu222.

PMID- 21847482
TI  - Hydrogen electrocatalysis on overlayers of rhodium over gold and palladium
      substrates--more active than platinum?
AB  - We have investigated the stability and catalytic activity of epitaxial overlayers
      of rhodium on Au(111) and Pd(111). Both surfaces show a strong affinity for
      hydrogen. We have calculated the energy of adsorption both for a strongly and a
      more weakly adsorbed species; the latter is the intermediate in the hydrogen
      evolution reaction. Both the energy of activation for hydrogen adsorption (Volmer
      reaction) and hydrogen recombination (Tafel reaction) are very low, suggesting
      that these overlayers are excellent catalysts.

PMID- 21847483
TI  - Femtosecond broadband time-resolved fluorescence and transient absorption study
      of the intramolecular charge transfer state of methyl 4-dimethylaminobenzoate.
AB  - A combined application of femtosecond broadband time-resolved fluorescence (fs
      TRF), fluorescence anisotropy (fs-TRFA) and fs to microsecond (MUs) transient
      absorption (TA) have been used to probe directly the dynamics, nature, formation
      and decay paths of the singlet intramolecular charge transfer ((1)ICT) state of
      methyl 4-dimethylaminobenzoate (1a) in acetonitrile. The result reveals explicit
      evidence for a common electronic origin (the L(a) nature) of the (1)ICT state and
      its precursor the locally excited ((1)LE) state to account jointly for the dual
      florescence known to this system. It also shows that the ICT reaction from the
      (1)LE to (1)ICT state occurs with time constant of ~0.8 ps and the (1)ICT state
      formed decays with a ~1.9 ns time constant leading mainly to a pipi* natured
      triplet state ((3)T(1)). The (3)T(1) then relaxes with a ~4 MUs lifetime under
      deoxygenated condition resulting in full recovery of the ground state (S(0)). As
      a case study, this work contributes novel experimental data for improved
      understanding of the mechanism of ICT reaction; it also reveals a distinct
      deactivation pattern for this prototype para-amino substituted aromatic carbonyl
      compound in acetonitrile.

PMID- 21847484
TI  - Anion-cation charge-transfer properties and spectral studies of
      [M(phen)3][Cd4(SPh)10] (M = Ru, Fe, and Ni).
AB  - Three anion-cation compounds 1-3 with formula [M(phen)(3)][Cd(4)(SPh)(10)].Sol (M
      = Ru(2+), Fe(2+), and Ni(2+), Sol = MeCN and H(2)O) have been synthesized and
      characterized by single-crystal analysis. Both the cations and anion are well
      known ions, but the properties of the co-assembled compounds are interesting.
      Molecular structures and charge-transfer between the cations and anions in
      crystal and even in solution are discussed. These compounds are isomorphous and
      short inter-ion interactions are found in these crystals, such as pi...pi
      stacking and C-H...pi contacts. Both spectroscopic and theoretical calculated
      results indicate that there is anion-cation charge-transfer (ACCT) between the Ru
      phen complex dye and the Cd-SPh cluster, which plays an important role in their
      photophysical properties. The intensity of the fluorescent emission of the
      [Ru(phen)(3)](2+) is enhanced when the cation interacts with the
      [Cd(4)(SPh)(10)](2-) anion. The mechanism for the enhancement of
      photoluminescence has been proposed.

PMID- 21847485
TI  - An effective Cu(II) quenching fluorescence sensor in aqueous solution and 1D
      chain coordination polymer framework.
AB  - In the article, a novel fluorescent probe for the copper cation based on
      fluorescence quenching mechanism was designed. It exhibited high selectivity for
      Cu(II) over other common metal ions in aqueous media. Furthermore the
      coordination between Cu(II) and the organic molecule sensor fabricated an
      interesting 1D chain coordination polymer framework.

PMID- 21847486
TI  - Exposure assessment for methyl and total mercury from seafood consumption in
      Korea, 2005 to 2008.
AB  - Reports on the occurrence and intake assessment of mercury for Korean seafood are
      currently not available. This is the first report to estimate the intake of
      methyl (Me-Hg) and total mercury (T-Hg) from seafood consumption in Korea. The
      concentrations of Me-Hg and T-Hg in seafood ranged from 1.02 to 780 (mean: 55.6)
      ng g(-1) wet weight and 4.89 to 1008 (mean: 100) ng g(-1) wet weight,
      respectively. The residue levels of Me-Hg and T-Hg in Korean seafood were
      moderate compared with those found in other countries. The methylation ratios of
      fish, cephalopods and crustaceans were similar, but shellfish had lower values
      compared with other species. The intakes of Me-Hg and T-Hg from seafood
      consumption for the general population were estimated to be 38.8 and 73.8 ng kg(
      1) body weight per day, respectively. Mackerel, tuna and squid made the highest
      contributions to the total intake of these contaminants. Among eight age groups,
      30-49 year and 3-6 year age groups had the highest exposure to Me-Hg and T-Hg.
      The concentrations and intakes of Me-Hg and T-Hg from Korean seafood were less
      than the allowable residue levels and threshold intake levels suggested by Korean
      and international authorities. The present study may be useful for risk
      management of mercury in Korean seafood.

PMID- 21847487
TI  - Synthesis of apiose-containing oligosaccharide fragments of the plant cell wall:
      fragments of rhamnogalacturonan-II side chains A and B, and apiogalacturonan.
AB  - Fragments of pectic polysaccharides rhamnogalacturonan-II (RG-II) and
      apiogalacturonan were synthesised using p-tolylthio apiofuranoside derivatives as
      key building blocks. Apiofuranose thioglycosides can be conveniently prepared by
      cyclization of the corresponding dithioacetals possessing a 2,3-O-isopropylidene
      group, which is required for preservation of the correct (3R) configuration of
      the apiofuranose ring. The remarkable stability of this protecting group in
      apiofuranose derivatives requires its replacement with a more reactive protecting
      group, such as a benzylidene acetal which was used in the synthesis of
      trisaccharide beta-Rhap-(1->3')-beta-Apif-(1->2)-alpha-GalAp-OMe. The X-ray
      crystal structure of the protected precursor of this trisaccharide has been
      elucidated.

PMID- 21847488
TI  - Synthetic polyion-counterion transport systems in polymersomes and gels.
AB  - Transport across the membranes of polymersomes remains difficult in part due to
      the great thickness of the polymer bilayers. Here, we report that dynamic polyion
      counterion transport systems are active in fluorogenic polymersomes composed of
      poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-PMOXA). These results
      suggest that counterion-activated calf-thymus DNA can act as cation carrier that
      moves not only across lipid bilayer and bulk chloroform membranes but also across
      the "plastic" membranes of polymersomes. Compared to egg yolk
      phosophatidylcholine (EYPC) lipsosomes, activities and activator scope in PDMS
      PMOXA polymersomes are clearly reduced. Embedded in agar gel matrices,
      fluorogenic PDMS-PMOXA polymersomes respond reliably to polyion-counterion
      transporters, with high contrast, high stability and preserved selectivity.
      Compared to standard EYPC liposomes, it cannot be said that PDMS-PMOXA
      polymersomes are better. However, they are different, and this difference could
      be interesting for the development of sensing devices.

PMID- 21847489
TI  - Polymer dewetting via stimuli responsive structural relaxation-contact angle
      analysis.
AB  - Thin films of a stimuli-responsive homopolymer dewet as a stimulus response after
      anion exchange of the imidazolium's counter anion. Contact angle analysis and
      interfacial energy considerations indicate dewetting goes counter to increasing
      spreading coefficient. Intrafilm stress arising from structural relaxation drives
      the dewetting.

PMID- 21847490
TI  - Quantitative genotyping of single nucleotide polymorphism by single-molecule
      multi-color fluorescence resonance energy transfer.
AB  - We developed a new single nucleotide polymorphism (SNP) genotyping method based
      on single-molecule multi-color fluorescence resonance energy transfer (FRET). We
      demonstrated that this new method uses less than 1 fmol of sample and is also
      highly quantitative with a detection level of 1% or lower in the minor allele
      fraction.

PMID- 21847491
TI  - Selective photocatalytic oxidation of aromatic alcohols to aldehydes in an
      aqueous suspension of gold nanoparticles supported on cerium(IV) oxide under
      irradiation of green light.
AB  - Gold nanoparticles supported on cerium(IV) oxide powder showing strong absorption
      at around 550 nm due to surface plasmon resonance oxidized aromatic alcohols to
      corresponding aldehydes almost quantitatively in an aqueous suspension under
      irradiation of green light.

PMID- 21847492
TI  - Simple and rapid quantification of gadolinium in urine and blood plasma samples
      by means of total reflection X-ray fluorescence (TXRF).
AB  - A simple and rapid method to determine gadolinium (Gd) concentrations in urine
      and blood plasma samples by means of total reflection X-ray fluorescence (TXRF)
      was developed. With a limit of detection (LOD) of 100 MUg L(-1) in urine and 80
      MUg L(-1) in blood plasma and a limit of quantification (LOQ) of 330 MUg L(-1) in
      urine and 270 MUg L(-1) in blood plasma, it allows analyzing urine samples taken
      from magnetic resonance imaging (MRI) patients during a period of up to 20 hours
      after the administration of Gd-based MRI contrast agents by means of TXRF. By
      parallel determination of the urinary creatinine concentration, it was possible
      to monitor the excretion kinetics of Gd from the patient's body. The Gd
      concentration in blood plasma samples, taken immediately after an MRI
      examination, could be determined after rapid and easy sample preparation by
      centrifugation. All measurements were validated with inductively coupled plasma
      mass spectrometry (ICP-MS). TXRF is considered to be an attractive alternative
      for fast and simple Gd analysis in human body fluids during daily routine in
      clinical laboratories.

PMID- 21847493
TI  - Preparation of curcumin loaded poly(epsilon-caprolactone)-poly(ethylene glycol)
      poly(epsilon-caprolactone) nanofibers and their in vitro antitumor activity
      against Glioma 9L cells.
AB  - The purpose of this work was to develop implantable curcumin-loaded poly(epsilon
      caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL,
      PCEC) nanofibers, which might have potential application in cancer therapy.
      Curcumin was incorporated into biodegradable PCEC nanofibers by electrospinning
      method. The surface morphology of the composite nanofibers was characterized on
      Scanning Electron Microscope (SEM). The average diameter of the nanofibers was
      2.3-4.5MUm. In vitro release behavior of curcumin from the fiber mats was also
      studied in detail. The in vitro cytotoxicity assay showed that the PCEC fibers
      themselves did not affect the growth of rat Glioma 9L cells. Antitumor activity
      of the curcumin-loaded fibers against the cells was kept over the whole
      experiment process, while the antitumor activity of pure curcumin disappeared
      within 48 h. These results strongly suggested that the curcumin/PCEC composite
      nanofibers might have potential application for postoperative chemotherapy of
      brain cancers.

PMID- 21847495
TI  - Anthranilic acid-based inhibitors of phosphodiesterase: design, synthesis, and
      bioactive evaluation.
AB  - Our previous studies identified two 2-benzoylaminobenzoate derivatives 1, which
      potently inhibited superoxide (O(2)(-)) generation induced by formyl-L-methionyl
      L-leucyl-L-phenylalanine (FMLP) in human neutrophils. In an attempt to improve
      their activities, a series of anthranilic acid derivatives were synthesized and
      their anti-inflammatory effects and underlying mechanisms were investigated in
      human neutrophils. Of these, compounds 17, 18, 46, 49, and 50 showed the most
      potent inhibitory effect on FMLP-induced release of O(2)(-) in human neutrophils
      with IC(50) values of 0.20, 0.16, 0.15, 0.06, and 0.29 MUM, respectively. SAR
      analysis showed that the activities of most compounds were dependent on the ester
      chain length in the A ring. Conversely, a change in the linker between the A and
      B ring from amide to sulfonamide or N-methyl amide, as well as exchanges in the
      benzene rings (A or B rings) by isosteric replacements were unfavorable. Further
      studies indicated that inhibition of O(2)(-) production in human neutrophils by
      these anthranilic acids was associated with an elevation in cellular cAMP levels
      through the selective inhibition of phosphodiesterase 4. Compound 49 could be
      approved as a lead for the development of new drugs in the treatment of
      neutrophilic inflammatory diseases.

PMID- 21847494
TI  - One-pot synthesis of N-F-Cr-doped anatase TiO2 microspheres with nearly all-(001)
      surface for enhanced solar absorption.
AB  - The synthesis and clarifications in structure-property relationship for anatase
      TiO(2) crystals exposing (001) facets have attracted much attention. In this
      paper, a novel titania microsphere with nearly all-(001) surface was synthesized
      by hydrothermal treatment of a thermal sprayed TiN/Ti coating with HF aqueous
      solution containing chromium powders. Unlike the conventional (001)-facet exposed
      anatase crystals, which are highly truncated bipyramids, the crystal achieved in
      the current investigation is drum-like with a round cross section. The formation
      of the drum-like crystals was contributed to a balance between the erosion and
      precipitation of anatase single crystallites. The Cr-doping in anatase was
      believed to increase the surface deficiency which enhanced the erosion procedure,
      leading to the drum-like crystals. The XPS analysis confirmed the incorporations
      of N, F and Cr in the microsized anatase crystals through the one-pot reaction,
      which led to a significantly enhanced solar absorption. The UV-Vis diffuse
      reflectance revealed a band-to-band red-shift of the band gap of the anatase
      crystals to 1.60 eV, which is contributed mainly to the homogeneous Cr-doping.

PMID- 21847496
TI  - Novel application of a Fe-Zn double-metal cyanide catalyst in the synthesis of
      biodegradable, hyperbranched polymers.
AB  - The use of Fe-Zn double-metal cyanide as a solid catalyst for synthesizing
      biodegradable, hyperbranched polymers from diacids and glycerol has been
      reported, for the first time, wherein acidity, micro-mesoporosity and
      hydrophobicity of the catalyst played an important role in controlling gelation.

PMID- 21847497
TI  - Molecular imprinting in Pickering emulsions: a new insight into molecular
      recognition in water.
AB  - Molecularly imprinted polymer microspheres were synthesized by Pickering emulsion
      polymerization. Fluorescence spectroscopic investigations provided insights into
      the template recognition in water.

PMID- 21847498
TI  - Triaminocyclopropenium salts as ionic liquids.
AB  - Salts of the charge-delocalised cations of the triaminocyclopropenium (tac)
      family bearing alkyl substituents have been prepared and shown to be air- and
      water-stable ionic liquids.

PMID- 21847499
TI  - Quality control of plant food supplements.
AB  - It is essential to guarantee the safety of unprocessed plants and food
      supplements if consumers' health is to be protected. Although botanicals and
      their preparations are regulated at EU level, at least in part, there is still
      considerable discretion at national level, and Member States may choose to
      classify a product either as a food supplement or as a drug. Accurate data
      concerning the finished products and the plant used as the starting point are of
      major importance if risks and safety are to be properly assessed, but in addition
      standardized criteria for herbal preparation must be laid down and respected by
      researchers and manufacturers. Physiologically active as well as potentially
      toxic constituents need to be identified, and suitable analytical methods for
      their measurement specified, particularly in view of the increasing incidence of
      economically motivated adulteration of herbal raw materials and extracts. It
      remains the duty of food operators to keep up with the scientific literature and
      to provide sufficient information to enable the adaptation of specifications,
      sampling schemes and analytical methods to a fast-changing environment.

PMID- 21847500
TI  - Traffic of leukocytes in microfluidic channels with rectangular and rounded cross
      sections.
AB  - Traffic of leukocytes in microvascular networks (particularly through arteriolar
      bifurcations and venular convergences) affects the dynamics of capillary blood
      flow, initiation of leukocyte adhesion during inflammation, and localization and
      development of atherosclerotic plaques in vivo. Recently, a growing research
      effort has been focused on fabricating microvascular networks comprising
      artificial vessels with more realistic, rounded cross-sections. This paper
      investigated the impact of the cross-sectional geometry of microchannels on the
      traffic of leukocytes flowing with human whole blood through a non-symmetrical
      bifurcation that consisted of a 50 MUm mother channel bifurcating into 30 MUm and
      50 MUm daughter branches. Two versions of the same bifurcation comprising
      microchannels with rectangular and rounded cross-sections were fabricated using
      conventional multi-layer photolithography to produce rectangular microchannles
      that were then rounded in situ using a recently developed method of liquid
      PDMS/air bubble injection. For microchannels with rounded cross-sections, about
      two-thirds of marginated leukocytes traveling along a path in the top plane of
      the bifurcation entered the smallest 30 MUm daughter branch. This distribution
      was reversed in microchannels with rectangular cross-sections--the majority of
      leukocytes traveling along a similar path continued to follow the 50 MUm
      microchannels after the bifurcation. This dramatic difference in the distribution
      of leukocyte traffic among the branches of the bifurcation can be explained by
      preferential margination of leukocytes towards the corners of the 50 MUm mother
      microchannels with rectangular cross-sections, and by the additional hindrance to
      leukocyte entry created by the sharp transition from the 50 MUm mother
      microchannel to the 30 MUm daughter branch at the intersection. The results of
      this study suggest that the trajectories of marginated leukocytes passing through
      non-symmetrical bifurcations are significantly affected by the cross-sectional
      geometry of microchannels and emphasize the importance of using microfludic
      systems with geometrical configurations closely matching physiological
      configurations when modeling the dynamics of whole blood flow in the
      microcirculation.

PMID- 21847501
TI  - Device and SPICE modeling of RRAM devices.
AB  - We report the development of physics based models for resistive random-access
      memory (RRAM) devices. The models are based on a generalized memristive system
      framework and can explain the dynamic resistive switching phenomena observed in a
      broad range of devices. Furthermore, by constructing a simple subcircuit, we can
      incorporate the device models into standard circuit simulators such as SPICE. The
      SPICE models can accurately capture the dynamic effects of the RRAM devices such
      as the apparent threshold effect, the voltage dependence of the switching time,
      and multi-level effects under complex circuit conditions. The device and SPICE
      models can also be readily expanded to include additional effects related to
      internal state changes, and will be valuable to help in the design and simulation
      of memory and logic circuits based on resistive switching devices.

PMID- 21847502
TI  - Slice imaging and wave packet study of the photodissociation of CH3I in the blue
      edge of the A-band: evidence of reverse 3Q0 <- 1Q1 non-adiabatic dynamics.
AB  - The photodissociation of CH(3)I in the blue edge (217-230 nm) of the A-band has
      been studied using a combination of slice imaging and resonance enhanced
      multiphoton ionization (REMPI) detection of the CH(3) fragment in the vibrational
      ground state (nu = 0). The profiles of the CH(3) (nu = 0) kinetic energy
      distributions and the photofragment anisotropies are interpreted in terms of the
      contribution of the excited surfaces involved in the photodissociation process,
      as well as the probability of non-adiabatic curve crossing between the (3)Q(0)
      and (1)Q(1) states. In the studied region, unlike in the central part of the A
      band where absorption to the (3)Q(0) state dominates, the I((2)P(J)), with J =
      1/2, 3/2, in correlation with CH(3) (nu = 0) kinetic energy distributions show
      clearly two contributions of different anisotropy, signature of the competing
      adiabatic and non-adiabatic dynamics, whose ratio strongly depends on the
      photolysis wavelength. The experimental results are compared with multisurface
      wave packet calculations carried out using the available ab initio potential
      energy surfaces, transition moments, and non-adiabatic couplings, employing a
      reduced dimensionality model. A good qualitative agreement is found between
      experiment and theory and both show evidence of reverse (3)Q(0)<-(1)Q(1) non
      adiabatic dynamics at the bluest excitation wavelengths both in the fragment
      kinetic energy and angular distributions.

PMID- 21847503
TI  - Electrochemical identification of artificial oligonucleotides related to bovine
      species. Potential for identification of species based on mismatches in the
      mitochondrial cytochrome C1 oxidase gene.
AB  - Our studies show that electrochemical impedance spectroscopy (EIS) and scanning
      electrochemical microscopy (SECM) of films of ds-DNA on gold allow us to
      distinguish between mitochondrial DNA fragments of the cytochrome c(1) oxidase
      (mt-Cox1) of three related species of the subfamily 'Bovinae' (Bos taurus, Bison
      bison, and Bison bonasus). In EIS, a perfectly matched DNA gives rise to a
      considerably larger charge transfer resistance R(ct) compared to mismatched
      pairings. Differences in charge transfer resistance, DeltaR(ct), before and after
      the addition of Zn(2+) ions provide an additional tool for identification. In
      addition, all ds-DNA films were studied by SECM and their kinetic parameters were
      determined. Perfectly matched ds-DNAs are readily distinguished from mismatched
      duplexes by their lower rate constants. Our system can be used multiple times by
      dehybridization and rehybridization of capture strands up to the 250 pmole level.

PMID- 21847504
TI  - Direct and simultaneous determination of Co and Cu on a silicon wafer using a
      chemiluminescence system.
AB  - In this work, we developed a drop-type chemiluminescence (CL) system with a
      partial least squares (PLS) calibration in which the coaxial optical fiber
      sensing head was developed for sampling and detection to determine Cu(2+) and
      Co(2+) on a silicon wafer directly. The use of time-resolved signal generation
      and PLS calibration in addition to CL allowed us to determine the metal ions
      simultaneously and selectively, based on the kinetic difference of Cu and Co ions
      in the luminol-H(2)O(2) system. Two component mixtures with a set of 15 wafer
      fragments were orthogonally calibrated. After prediction test, the method was
      applied to an intentionally contaminated silicon wafer and validated by
      inductively coupled plasma-mass spectrometer (ICP-MS) measurement with a HF
      HNO(3) scanning solution. The average concentrations of Cu(2+) and Co(2+) of 3.45
      (+/-0.95) * 10(13) and 2.30 (+/-1.18) * 10(11) atoms per cm(2), respectively,
      were obtained, which were very close to the ICP-MS results of 3.70 * 10(13) for
      Cu(2+) and 2.46 * 10(11) atoms per cm(2) for Co(2+). In conclusion, this drop
      mode CL showed almost more than 10 times better reproducibility than the typical
      batch mode for the profile measurement. Moreover, the adoption of PLS calibration
      added the function of selectivity for the simultaneous determination to this CL
      system, in addition to the direct mapping capability for the solid surface
      analysis.

PMID- 21847505
TI  - Detecting mild COPD is not a waste of resources.

PMID- 21847506
TI  - Non-communicable diseases and their importance in low and middle income
      countries.

PMID- 21847507
TI  - Sensitization and chronic beryllium disease at a primary manufacturing facility,
      part 2: validation of historical exposures.
AB  - OBJECTIVE: The aim of this study was to evaluate the validity of a job exposure
      matrix (JEM) constructed for the period 1994-1999. Historical exposure estimates
      (HEE) for the JEM were constructed for all job and year combinations by applying
      temporal factors reflecting annual change in area air measurements (1994-1998) to
      the personal baseline exposure estimates (BEE) collected in 1999. The JEM was
      generated for an epidemiologic study to examine quantitative exposure-response
      relationships with sensitization and chronic beryllium disease. METHODS: The
      validity of the BEE and HEE was evaluated by comparing them with a validation
      dataset of independently collected personal beryllium exposure measurements from
      1999 and 1994-1998, respectively. Agreement between the JEM and validation data
      was assessed using relative bias and concordance correlation coefficients (CCC).
      RESULTS: The BEE and HEE overestimated the measured exposures in their respective
      validation datasets by 8% and 6%, respectively. The CCC reflecting the deviation
      of the fitted line from the concordance line, showed good agreement for both BEE
      (CCC=0.80) and HEE (CCC=0.72). Proportional difference did not change with
      exposure levels or by process area and year. Overall, the agreement between the
      JEM and validation estimates (from combined HEE and BEE) was high (CCC=0.77).
      CONCLUSIONS: This study demonstrated that the reconstructed beryllium exposures
      at a manufacturing facility were reliable and can be used in epidemiologic
      studies.

PMID- 21847508
TI  - Immunohistochemical expression of von Willebrand factor in the preeclamptic
      placenta.
AB  - Preeclampsia is a high-prevalence systemic pregnancy disorder associated with
      maternal and foetal mortality. Its pathogenesis is unknown, but it is thought
      that oxidative stress and endothelial dysfunction may play a fundamental role.
      Von Willebrand factor (vWF), a marker of endothelial cell injury, can be found in
      different cells and zones of the placenta. To determine the differential
      immunoexpression of vWF at different tissue types of preeclamptic placenta and
      endothelial dysfunction markers at maternal serum of preeclamptic pregnancies. A
      case-control study was performed on a population of pregnant women with
      preeclampsia (n = 14), and normal pregnancies (n = 8). Placental and blood plasma
      samples were withdrawn at delivery. Immunohistochemical vWF expression in the
      placental tissue was determined. Endothelial dysfunction was assessed through
      plasminogen activator inhibitor (PAI) 1 and 2 ratio and vWF concentration in
      maternal plasma. P values less than 0.05 were considered statistically
      significant. Preeclamptic women showed increased plasma PAI-1/PAI-2 ratio (P <
      0.05). There was diminished placental vWF expression in syncytiotrophoblast and
      increased in the intervillous space of preeclamptic placentas (P < 0.05). No
      significant differences in vWF expression were found in the villous endothelium
      and stroma, but it was significantly higher in maternal plasma (P < 0.05). In
      preeclampsia occurs endothelial damage and placental cell injury. Cell damage in
      syncytiotrophoblast that occurs in preeclampsia could liberate vWF from
      syncytiotrophoblast to the placental intervillous space, and this may have
      pathogenic implications.

PMID- 21847509
TI  - A novel role of Rho-kinase in the regulation of ligand-induced phosphorylated
      EGFR endocytosis via the early/late endocytic pathway in human fibrosarcoma
      cells.
AB  - The small GTPase RhoA and its downstream effectors, the Rho-associated kinase
      (Rho-kinase) family, are known to regulate cell morphology, motility, and tumor
      progression via the regulation of actin cytoskeleton rearrangement. In the
      present study, we evaluated the role of Rho-kinase in the intracellular endocytic
      trafficking of ligand-induced phosphorylated epidermal growth factor receptor
      (pEGFR). We investigated the time course of the internalization fate of EGF
      induced pEGFR via the early/late endocytic pathway in human fibrosarcoma cell
      line HT1080 cells using Y-27632, a selective Rho-kinase inhibitor. We found,
      using confocal immunofluorescence microscopy and Western blot analysis, a large
      accumulation of pEGFR in the nuclei of HT1080 cells. In contrast, we observed
      decreased amounts of the pEGFR-positive staining in the nuclei along with an
      accumulation of cytosolic pEGFR staining when the cells were incubated for 15-30
      min in the presence of Y-27632, implying that an aberrant endocytic trafficking
      mechanism of pEGFR occurs in HT1080 cells whereby pEGFR might be selectively
      translocated into the nucleus. Moreover, we demonstrated that after 15-min of
      stimulation with Texas Red-EGF, increasing numbers of pEGFR-positive staining
      that had colocalized with Texas Red-EGF-positive punctate staining were seen in
      the cytoplasm of HT1080 cells but after 30-min of stimulation, most of this
      staining had disappeared from the cytoplasm and a large accumulation of pEGFR
      positive staining appeared in the nucleus. Thus, nuclear accumulation of pEGFR
      appears to occur in an EGF-dependent manner. In contrast, such nuclear pEGFR
      positive staining was not seen in the Y-27632-treated cells. Furthermore,
      silencing of RhoA or Rho-kinases I/II by sequence specific siRNAs considerably
      inhibited the EGF-dependent nuclear accumulation of pEGFR. Collectively, these
      results provide the first evidence that Rho-kinase signaling pathway plays a
      suppressive role in the intracellular vesicle trafficking of pEGFR via the
      endocytic pathway and that an increased Rho-kinase activity leads to the
      attenuation of the normal endocytic vesicular traffic of pEGFR via the early/late
      endocytic pathway, instead causing pEGFR to be trafficked out of the endocytic
      vesicles into the nucleus.

PMID- 21847510
TI  - Methanotrophic community structure and activity under warming and grazing of
      alpine meadow on the Tibetan Plateau.
AB  - Knowledge about methanotrophs and their activities is important to understand the
      microbial mediation of the greenhouse gas CH(4) under climate change and human
      activities in terrestrial ecosystems. The effects of simulated warming and sheep
      grazing on methanotrophic abundance, community composition, and activity were
      studied in an alpine meadow soil on the Tibetan Plateau. There was high abundance
      of methanotrophs (1.2-3.4 * 10(8) pmoA gene copies per gram of dry weight soil)
      assessed by real-time PCR, and warming significantly increased the abundance
      regardless of grazing. A total of 64 methanotrophic operational taxonomic units
      (OTUs) were obtained from 1,439 clone sequences, of these OTUs; 63 OTUs (98.4%)
      belonged to type I methanotrophs, and only one OTU was Methylocystis of type II
      methanotrophs. The methanotroph community composition and diversity were not
      apparently affected by the treatments. Warming and grazing significantly enhanced
      the potential CH(4) oxidation activity. There were significantly negative
      correlations between methanotrophic abundance and soil moisture and between
      methanotrophic abundance and NH(4)-N content. The study suggests that type I
      methanotrophs, as the dominance, may play a key role in CH(4) oxidation, and the
      alpine meadow has great potential to consume more CH(4) under future warmer and
      grazing conditions on the Tibetan Plateau.

PMID- 21847511
TI  - Sorption-assisted surface conjugation: a way to stabilize laccase enzyme.
AB  - Enyzme immobilization on solid surfaces is one of the most relevant methods to
      improve enzyme activity and stability under harsh conditions over extended
      periods. A typically interesting application is the immobilization of laccases,
      multicopper enzymes oxidizing aromatic compounds, to solid surfaces in order to
      develop valuable tools for the elimination of micropollutants in wastewater.
      Laccase of the white-rot fungus Coriolopsis polyzona has been successfully
      immobilized on fumed silica nanoparticles using a novel method. It consists in
      the sorption of the enzyme to amino-modified silica nanoparticles and the
      subsequent covalent cross-linking using glutaraldehyde as a homobifunctional
      linker. The so-produced nanoparticulate material has been characterized by means
      of scanning electron microscopy and Brunauer-Emmett-Teller surface area analysis
      revealing modifications of the surface structure and area during the coupling
      procedure. Laccase immobilization on spherical nanoparticles produced according
      to the method of Stober has been shown to be much less efficient than on fumed
      silica nanoparticles. Long-term stability assays revealed that the novel
      developed method allows a drastic stabilization of the enzyme. In real
      wastewater, 77% of the laccase activity remained on the nanoparticles over 1
      month, whereas the activity of free laccase dropped to 2.5%. The activity loss on
      the nanoparticles resulted from partial inactivation of the immobilized enzymes
      and additional release into the surrounding solution with subsequent fast
      inactivation of the free enzymes, since almost no activity was found in the
      supernatants.

PMID- 21847512
TI  - Exceptional thermal stability and organic solvent tolerance of an esterase
      expressed from a thermophilic host.
AB  - A protein expression system recently developed for the thermophilic crenarchaeon
      Sulfolobus islandicus was employed to produce recombinant protein for EstA, a
      thermophilic esterase encoded in the same organism. Large amounts of protein were
      readily obtained by an affinity protein purification, giving SisEstA. Upon
      Escherichia coli expression, only the thioredoxin-tagged EstA recombinant protein
      was soluble. The fusion protein was then purified, and removing the protein tag
      yielded EcSisEstA. Both forms of the thermophilic EstA enzyme were characterized.
      We found that SisEstA formed dimer exclusively in solution, whereas EcSisEstA
      appeared solely as monomer. The former exhibited a stronger resistance to organic
      solvents than the latter in general, having a much higher temperature optimum (90
      degrees C vs. 65 degrees C). More strikingly, SisEstA exhibited a half-life that
      was more than 32-fold longer than that of EcSisEstA at 90 degrees C. This
      indicated that thermophilic enzymes yielded from homologous expression should be
      better biocatalysts than those obtained from mesophilic expression.

PMID- 21847513
TI  - LAMP-based method for a rapid identification of Legionella spp. and Legionella
      pneumophila.
AB  - Legionella pneumophila is accounted for more than 80% of Legionella infection.
      However it is difficult to discriminate between the L. pneumophila and non-L.
      pneumophila species rapidly. In order to detect the Legionella spp. and
      distinguish L. pneumophila from Legionella spp., a real-time loop-mediated
      isothermal amplification (LAMP) platform that targets a specific sequence of the
      16S rRNA gene was developed. LS-LAMP amplifies the fragment of the 16S rRNA gene
      to detect all species of Legionella genus. A specific sequence appears at the 16S
      rRNA gene of L. pneumophila, while non-L. pneumophila strains have a variable
      sequence in this site, which can be recognized by the primer of LP-LAMP. In the
      present study, 61 reference strains were used for the method verification. We
      found that the specificity was 100% for both LS-LAMP and LP-LAMP, and the
      sensitivity of LAMP assay for L. pneumophila detection was between 52 and 5.2
      copies per reaction. In the environmental water samples detection, a total of 107
      water samples were identified by the method. The culture and serological test
      were used as reference methods. The specificity of LS-LAMP and LP-LAMP for the
      samples detection were 91.59% (98/107) and 93.33% (56/60), respectively. The
      sensitivity of LS-LAMP and LP-LAMP were 100% (51/51) and 100% (18/18). The
      results suggest that real-time LAMP, as a new assay, provides a specific and
      sensitive method for rapid detection and differentiation of Legionella spp. and
      L. pneumophila and should be utilized to test environmental water samples for
      increased rates of detection.

PMID- 21847514
TI  - [Receptor detection in breast cancer. A decade of quality assurance trials in
      German-speaking pathology].

PMID- 21847515
TI  - [Salivary gland tumors: pathology and prognosis].
AB  - Due to their infrequency, diagnosis of salivary gland tumors remains a challenge
      for the practicing pathologist with respect to subtyping, grading and estimating
      patient prognosis. In a 3 center collaborative study of 288 cases with clinical
      follow-up information, it could be demonstrated that apart from clinical
      parameters like high patient's age, male sex and high tumor stage, the
      application of a 3-tiered grading system incorporating the histological tumor
      type is of high prognostic relevance. In immunohistochemical and molecular
      analyses overexpression of epidermal growth factor receptor (EGFR), high
      expression of human epidermal growth factor receptor 2 (HER2), amplification and
      gains of EGFR and HER2, absent expression of C-KIT, loss of maspin and of O(6)
      methylguanine DNA-methyltransferase (MGMT) as well as MGMT promoter methylation
      turned out to be negative prognostic factors. In mucoepidermoid carcinomas the
      presence of a translocation t(11;19) was less relevant than recognizing different
      subtypes (classical type, eosinophilic, clear-cell and squamoid variants). Acinic
      cell carcinoma with mixed acinar-ductular differentiation as judged by expression
      of CK7 was characterized by a higher frequency of early relapse. The presented
      results underline the pathologist's role in the diagnosis and management of
      patients with salivary gland carcinomas.

PMID- 21847516
TI  - [Pathology of infectious diseases. Not a trivial topic].

PMID- 21847517
TI  - Functional outcomes of sleep in Thai patients with obstructive sleep-disordered
      breathing.
AB  - PURPOSES: Quality of life assessment in obstructive sleep-disordered breathing
      (OSDB) is increasingly recognized, and the functional outcomes of sleep
      questionnaire (FOSQ) is a popular instrument. The objective of this study was to
      apply this questionnaire in Thai patients to assess its reliability, validity,
      and responsiveness properties. METHODS: A total of 223 subjects were recruited.
      The scores of FOSQ in 38 healthy volunteers and 40 primary snorers were compared
      with those of 108 obstructive sleep apnea (OSA) patients diagnosed by
      polysomnography. Seventy-two subjects answered the FOSQ twice at 2-4 weeks apart
      to check the test-retest reliability, and 37 patients with OSA who complied well
      with CPAP therapy answered them again after treatment at 3-6 months. All
      participants also filled the Epworth sleepiness scales (ESS) to check the
      concurrent validity. RESULTS: There were statistically significant differences in
      all FOSQ subscales including global scores between healthy volunteers (17.3 +/-
      2.1) and OSA patients (14.5 +/- 2.9) (p < 0.001). The internal consistency of the
      questionnaire was excellent (Cronbach's alpha 0.95), and the test-retest
      reliability (intra-class correlation coefficients) was 0.70 in global scores.
      After adequate CPAP therapy, all FOSQ scores increased significantly (p < 0.001)
      There were significant correlations between all FOSQ scores except sexual
      relationship and ESS (r -0.48); however, these had only a weak relationship with
      AHI and minimal oxygen saturation. CONCLUSIONS: The FOSQ can be applied to Thai
      patients with OSDB with good reliability, validity, and responsiveness
      properties. It may be the first validated version of FOSQ in East Asian countries
      which is a very useful tool for future research.

PMID- 21847518
TI  - Efficacy and safety of moxifloxacin for community-acquired bacterial pneumonia
      based on pharmacokinetic analysis.
AB  - Moxifloxacin is a respiratory quinolone that is expected to be useful for
      treating community-acquired bacterial pneumonia, but few clinical studies and not
      a detailed evaluation of its pharmacokinetics have been conducted in Japan in
      patients with pneumonia. We assessed the efficacy and safety of moxifloxacin in
      18 patients with community-acquired bacterial pneumonia using pharmacokinetic
      pharmacodynamic analysis. There was significant improvement in body temperature,
      white blood cell count, C-reactive protein, and chest X-ray score on day 3 of
      moxifloxacin treatment, which persisted until the completion of treatment (all p
      < 0.05). Nine strains, including Streptococcus pneumoniae, Moraxella catarrhalis,
      Haemophilus influenzae, and Enterobacter cloacae, were isolated from sputum
      cultures of nine patients. The isolated strains were eradicated by moxifloxacin.
      The mean area under the concentration-time curve from 0 to 24 hours [AUC(0-24 h)
      (AUC(0-24 h,ss))], maximum plasma concentration (C(max)), and trough plasma level
      (C(trough)) of moxifloxacin at steady state was 52.0 MUg h/ml, 4.5, and 0.9
      MUg/ml, respectively. Mean AUC(0-24 h,ss)/mimimum inhibitory concentration (MIC),
      and C(max)/MIC ratios for patients in whom MICs of moxifloxacin were determined
      for pathogenic bacteria were 723 and 62, respectively. The median AUC(0-24
      h,ss)/MIC and C(max)/MIC ratios (based on Monte Carlo simulation employing MICs
      for 257 strains of S. pneumoniae collected during a respiratory infection survey
      by the Japanese Society of Chemotherapy in 2007) were 209.56 and 17.88,
      respectively. Thus, when the target for the AUC/MIC ratio was set at >=30 and
      that for the C(max)/MIC ratio at >=5, the achievement rate for these two
      parameters was 97.36% and 96.71%, respectively. Two patients (11%) experienced
      three adverse effects [one nausea, another increased aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT)], but the events were not serious. Based
      on these results, moxifloxacin (400 mg once daily) was considered useful for
      treating community-acquired bacterial pneumonia and is expected to show excellent
      efficacy and safety as well as suppressing the emergence of resistance.

PMID- 21847519
TI  - Treatment strategy based on targeting P-glycoprotein on peripheral lymphocytes in
      patients with systemic autoimmune disease.
AB  - Although corticosteroids, immunosuppressants and disease-modifying antirheumatic
      drugs (DMARDs) are widely used in the treatment of various systemic autoimmune
      diseases such as systemic lupus erythematosus (SLE), we often experience patients
      with systemic autoimmune diseases who are resistant to these treatments. P
      glycoprotein (P-gp) of membrane transporters, a product of the multiple drug
      resistance (MDR)-1 gene, is known to play a pivotal role in the acquisition of
      drug resistance to chemotherapy in malignancy. However, the relevance of MDR-1
      and P-gp to resting and activated lymphocytes, which are the major target in the
      treatment of systemic autoimmune diseases, remains unclear. Studies from our
      laboratories found surface expression of P-gp on peripheral lymphocytes in
      patients with SLE and a significant correlation between the expression level and
      disease activity. Such expression is induced not only by genotoxic stresses but
      also by various stimuli including cytokines, resulting in active efflux of drugs
      from the cytoplasm of lymphocytes, resulting in drug-resistance and high disease
      activity. However, the use of both P-gp antagonists (e.g., cyclosporine) and
      inhibition of P-gp synthesis with intensive immunosuppressive therapy
      successfully reduces the efflux of corticosteroids from lymphocytes in vitro,
      suggesting that P-gp antagonists and P-gp synthesis inhibitors could be used to
      overcome drug-resistance in vivo and improve outcome. In conclusion, lymphocytes
      activated by various stimuli in patients with highly active disease apparently
      acquire MDR-1-mediated multidrug resistance against corticosteroids and probably
      some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could
      overcome such drug resistance. The expression of P-gp on lymphocytes is a
      promising marker of drug resistance and a suitable target to combat drug
      resistance in patients with active systemic autoimmune diseases.

PMID- 21847520
TI  - A case of angiomyolipoma of the renal sinus.
AB  - The case of a 63-year-old woman with a relatively rapidly growing angiomyolipoma
      (AML) originating from the right renal sinus is presented. The tumor had enlarged
      to more than fivefold in volume (7.4 * 6.7 * 10.1 cm) in the 7 years following
      its detection (5.6 * 3.4 * 4.6 cm) and had significantly pushed aside the
      duodenum and the inferior vena cava. The tumor was surgically resected together
      with the right kidney, and pathological examination revealed AML originating from
      the renal sinus. An AML involving or originating from the renal sinus is
      exceedingly rare; only 14 cases have been reported. Rapidly growing AMLs of the
      renal sinus are difficult to differentiate from liposarcoma because of similar
      findings in imaging studies. It should be noted that AML of the renal sinus can
      be a differential diagnosis of retroperitoneal fatty mass. Furthermore, an
      enlarged AML in the renal sinus may push aside other organs, such as the ileum,
      pancreas, and major vessels. Clinicians should determine whether these patients
      should be placed under active surveillance or be treated with invasive measures,
      such as radical nephrectomy.

PMID- 21847521
TI  - Long-term complete response to very-low-dose interleukin-2 therapy in patients
      with metastatic renal cell carcinoma: report of two cases.
AB  - Before the advent of molecular-targeted agents, immunotherapy using cytokines,
      such as interferon-alpha (IFN-alpha) and interleukin-2 (IL-2), had been the
      mainstay of treatment for patients with metastatic renal cell carcinoma (mRCC),
      and this therapy may still be occasionally recommended for such patients. In this
      report, we present two cases of mRCC who were treated with very-low-dose IL-2
      therapy and subsequently achieved complete response (CR). Both cases received
      adjuvant IFN-alpha therapy following radical nephrectomy; however, multiple lung
      metastases developed 4 and 12 months after surgery, and low-dose IL-2 (0.7
      million U/day) was then administered twice per week for 14 and 35 months,
      respectively. In both cases, metastatic lesions completely regressed 3 and 20
      months after the start of IL-2 therapy, and these responses have persisted for 81
      and 67 months, respectively, to date. These findings suggest that immunotherapy
      with IL-2, even at a very-low-dose setting, may achieve the induction of CR in
      mRCC; accordingly, IL-2-based immunotherapy should be considered as the initial
      treatment for appropriately selected patients with mRCC.

PMID- 21847522
TI  - A case of idiopathic nodular glomerulosclerosis with fibrin caps.
AB  - We report a case of idiopathic nodular glomerulosclerosis (ING) mimicking
      diabetic Kimmelstiel-Wilson glomerulopathy. A 72-year-old man suffering from
      nephritic syndrome and renal dysfunction had no prior history of diabetes
      mellitus, but had impaired glucose tolerance and a history of hypertension and
      smoking. A kidney biopsy showed increased mesangial matrix with Kimmelstiel
      Wilson-like nodules, glomerular basement membrane thickening and capillary
      microaneurysms. Additionally, a large amount of fibrin caps detectable as
      electron-dense subendothelial material by electron microscopy were observed.
      Although ING with fibrin caps has been rarely reported, the large number of
      fibrin caps seen in this case may be due to the advanced clinical stage.

PMID- 21847524
TI  - Kinetics of effector functions and phenotype of virus-specific and gammadelta T
      lymphocytes in primary human cytomegalovirus infection during pregnancy.
AB  - The T-cell response to human cytomegalovirus (HCMV) primary infection was
      analyzed in 27 pregnant women during the first year after primary HCMV infection.
      Pregnant women with remote HCMV infection were enrolled as controls. Interferon
      gamma-producing T cells were readily detected at levels comparable (CD4(+)) or
      higher (CD8(+)) than controls, whereas the CD4(+) and CD8(+) lymphoproliferative
      response as well as IL-2 production was significantly reduced with respect to
      controls for at least 9 months after infection. In addition, CD45RA re-expression
      as well as cytotoxic T lymphocyte activity and perforin expression were the major
      components of the adaptive CD4(+) and CD8(+) T-cell immune response, while
      Vdelta2(-) gammadelta T-cell expansion in response to HCMV infection followed
      kinetics similar to that of CD8(+) T cells. Reduced CD45RA re-expression directly
      correlated with HCMV transmission to the fetus, thus providing an important
      prognostic parameter.

PMID- 21847525
TI  - Donor-acceptor compound based on rhodanineacetic acid-pyrene derivative: red
      light emitting fluorescent organic nanoparticles.
AB  - A donor-acceptor compound based on Rhodanineacetic acid-pyrene derivative (RAAP),
      which emits weak yellow-green fluorescence in the methanol solution, was
      investigated. RAAP nanoparticles with a mean diameter of 50-60 nm were prepared
      by a simple reprecipitation method without surfactants. The observation of RAAP
      nanoparticles were undertaken through SEM and TEM method. The emission spectra of
      RAAP nanoparticles are red-shifted (Delta lambda(em) = 86 nm) to red region and
      the intensity is 40-fold higher than that in the methanol solution. Both the J
      aggregation and aggregation-induced intramolecular planarization are considered
      to be the probable mechanism of strong emission for RAAP nanoparticles. The
      excellent sensibility toward organic vapor which profits from its fluorescence
      switching behavior is well demonstrated by vapor experiment.

PMID- 21847526
TI  - Rapid and cost-effective screening of newly identified microsatellite loci by
      high-resolution melting analysis.
AB  - This study describes a new method for identifying microsatellite loci that will
      reliably amplify and show high degree of polymorphism in a given species.
      Microsatellites are the most powerful codominant markers available today, but the
      development of novel loci remains a labour-intensive and expensive process. In de
      novo isolation, approaches using next generation sequencing (NGS) are gradually
      replacing ones using Escherichia coli libraries, resulting in unparalleled
      numbers of candidate loci available. We present a systematic review of published
      microsatellite primer notes and show that, on average, about half of all
      candidate loci are lost due to insufficient PCR amplification, monomorphism or
      multicopy status in the genome, no matter what isolation strategy is used. Thus,
      the screening of candidate loci remains a major step in marker development. Re
      assessing capillary-electrophoresis genotyped loci via high-resolution melting
      analysis (HRM), we evaluate the usefulness of HRM for this step. We demonstrate
      its applicability in a genotyping case study and introduce a fast, HRM-based
      workflow for the screening of microsatellite loci. This workflow may readily be
      applied to NGS-based marker development and has the potential to cut the costs of
      traditional testing by half to three quarters.

PMID- 21847523
TI  - Tyrosine kinase inhibitors ameliorate autoimmune encephalomyelitis in a mouse
      model of multiple sclerosis.
AB  - Multiple sclerosis is an autoimmune disease of the central nervous system
      characterized by neuroinflammation and demyelination. Although considered a T
      cell-mediated disease, multiple sclerosis involves the activation of both
      adaptive and innate immune cells, as well as resident cells of the central
      nervous system, which synergize in inducing inflammation and thereby
      demyelination. Differentiation, survival, and inflammatory functions of innate
      immune cells and of astrocytes of the central nervous system are regulated by
      tyrosine kinases. Here, we show that imatinib, sorafenib, and GW2580-small
      molecule tyrosine kinase inhibitors-can each prevent the development of disease
      and treat established disease in a mouse model of multiple sclerosis. In vitro,
      imatinib and sorafenib inhibited astrocyte proliferation mediated by the tyrosine
      kinase platelet-derived growth factor receptor (PDGFR), whereas GW2580 and
      sorafenib inhibited macrophage tumor necrosis factor (TNF) production mediated by
      the tyrosine kinases c-Fms and PDGFR, respectively. In vivo, amelioration of
      disease by GW2580 was associated with a reduction in the proportion of
      macrophages and T cells in the CNS infiltrate, as well as a reduction in the
      levels of circulating TNF. Our findings suggest that GW2580 and the FDA-approved
      drugs imatinib and sorafenib have potential as novel therapeutics for the
      treatment of autoimmune demyelinating disease.

PMID- 21847527
TI  - Determination of perfluorinated compounds in mollusks by matrix solid-phase
      dispersion and liquid chromatography-tandem mass spectrometry.
AB  - Perfluorinated compounds (PFCs) have been used for over 40 years in different
      commercial and industrial applications mainly as surfactants and surface
      protectors and have become an important class of marine emerging pollutants. This
      study presents the development and validation of a new analytical method to
      determine the simultaneous presence of eight PFCs in different kinds of mollusks
      using matrix solid-phase dispersion (MSPD) followed by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Simplicity of the analytical procedure, low
      volume of solvent and quantity of sample required, low global price, and
      integration of extraction and clean-up into a single step, are the most important
      advantages of the developed methodology. Solvent, solid support (dispersing
      agent), clean-up sorbent, and their amounts were optimized by means of an
      experimental design. In the final method, 0.5 g of sample are dispersed with 0.2
      g of diatomaceous earth and transferred into a polypropylene syringe containing 4
      g of silica as clean-up sorbent. Then, analytes are eluted with 20 mL of
      acetonitrile. The extract is finally concentrated to a final volume of 0.5 mL in
      methanol, avoiding extract dryness in order to prevent evaporation losses and
      injected in the LC-MS/MS. The combination of this MSPD protocol with LC-MS/MS
      afforded detection limits from 0.05 to 0.3 ng g(-1). Also, a good linearity was
      established for the eight PFCs in the range from limit of quantification (LOQ) to
      500 ng mL(-1) with R(2) > 0.9917. The recovery of the method was studied with
      three types of spiked mollusk and was in the 64-126% range. Moreover, a mussel
      sample was spiked and aged for more than 1 month and analyzed by the developed
      method and a reference method, ion-pair extraction, for comparison, producing
      both methods statistically equal concentration values. The method was finally
      applied to the determination of PFCs in different kinds of mollusks revealing
      concentrations up to 8.3 ng g(-1) for perfluoroundecanoic acid.

PMID- 21847528
TI  - Physisorbed surface coatings for poly(dimethylsiloxane) and quartz microfluidic
      devices.
AB  - Surface modifications of microfluidic devices are of essential importance for
      successful bioanalytical applications. Here, we investigate three different
      coatings for quartz and poly(dimethylsiloxane) (PDMS) surfaces. We employed a
      triblock copolymer with trade name F(108), poly(L-lysine)-g-poly(ethylene glycol)
      (PLL-PEG), as well as the hybrid coating n-dodecyl-beta-D-maltoside and methyl
      cellulose (DDM/MC). The impact of these coatings was characterized by measuring
      the electroosmotic flow (EOF), contact angle, and prevention of protein
      adsorption. Furthermore, we investigated the influence of static coatings, i.e.,
      the incubation with the coating agent prior to measurements, and dynamic
      coatings, where the coating agent was present during the measurement. We found
      that all coatings on PDMS as well as quartz reduced EOF, increased
      reproducibility of EOF, reduced protein adsorption, and improved the wettability
      of the surfaces. Among the coating strategies tested, the dynamic coatings with
      DDM/MC and F(108) demonstrated maximal reduction of EOF and protein adsorption
      and simultaneously best long-term stability concerning EOF. For PLL-PEG, a
      reversal in the EOF direction was observed. Interestingly, the static surface
      coating strategy with F(108) proved to be as effective to prevent protein
      adsorption as dynamic coating with this block copolymer. These findings will
      allow optimized parameter choices for coating strategies on PDMS and quartz
      microfluidic devices in which control of EOF and reduced biofouling are
      indispensable.

PMID- 21847529
TI  - Arsenopyrite and pyrite bioleaching: evidence from XPS, XRD and ICP techniques.
AB  - In this work, a multi-technical bulk and surface analytical approach was used to
      investigate the bioleaching of a pyrite and arsenopyrite flotation concentrate
      with a mixed microflora mainly consisting of Acidithiobacillus ferrooxidans. X
      ray diffraction, X-ray photoelectron spectroscopy (XPS) and X-ray-induced Auger
      electron spectroscopy mineral surfaces investigations, along with inductively
      coupled plasma-atomic emission spectroscopy and carbon, hydrogen, nitrogen and
      sulphur determination (CHNS) analyses, were carried out prior and after
      bioleaching. The flotation concentrate was a mixture of pyrite (FeS(2)) and
      arsenopyrite (FeAsS); after bioleaching, 95% of the initial content of pyrite and
      85% of arsenopyrite were dissolved. The chemical state of the main elements (Fe,
      As and S) at the surface of the bioreactor feed particles and of the residue
      after bioleaching was investigated by X-ray photoelectron and X-ray excited Auger
      electron spectroscopy. After bioleaching, no signals of iron, arsenic and sulphur
      originating from pyrite and arsenopyrite were detected, confirming a strong
      oxidation and the dissolution of the particles. On the surfaces of the mineral
      residue particles, elemental sulphur as reaction intermediate of the leaching
      process and precipitated secondary phases (Fe-OOH and jarosite), together with
      adsorbed arsenates, was detected. Evidence of microbial cells adhesion at mineral
      surfaces was also produced: carbon and nitrogen were revealed by CHNS, and
      nitrogen was also detected on the bioleached surfaces by XPS. This was attributed
      to the deposition, on the mineral surfaces, of the remnants of a bio-film
      consisting of an extra-cellular polymer layer that had favoured the bacterial
      action.

PMID- 21847530
TI  - Trace analysis of environmental matrices by large-volume injection and liquid
      chromatography-mass spectrometry.
AB  - The time-honored convention of concentrating aqueous samples by solid-phase
      extraction (SPE) is being challenged by the increasingly widespread use of large
      volume injection (LVI) liquid chromatography-mass spectrometry (LC-MS) for the
      determination of traces of polar organic contaminants in environmental samples.
      Although different LVI approaches have been proposed over the last 40 years, the
      simplest and most popular way of performing LVI is known as single-column LVI (SC
      LVI), in which a large-volume of an aqueous sample is directly injected into an
      analytical column. For the purposes of this critical review, LVI is defined as an
      injected sample volume that is >=10% of the void volume of the analytical column.
      Compared with other techniques, SC-LVI is easier to set up, because it requires
      only small hardware modifications to existing autosamplers and, thus, it will be
      the main focus of this review. Although not new, SC-LVI is gaining acceptance and
      the approach is emerging as a technique that will render SPE nearly obsolete for
      many environmental applications. In this review, we discuss: the history and
      development of various forms of LVI; the critical factors that must be considered
      when creating and optimizing SC-LVI methods; and typical applications that
      demonstrate the range of environmental matrices to which LVI is applicable, for
      example drinking water, groundwater, and surface water including seawater and
      wastewater. Furthermore, we indicate direction and areas that must be addressed
      to fully delineate the limits of SC-LVI.

PMID- 21847531
TI  - Microanalysis of the antiretroviral nevirapine in human hair from HIV-infected
      patients by liquid chromatography-tandem mass spectrometry.
AB  - Sufficient drug exposure is crucial for maintaining durable responses to HIV
      treatments. However, monitoring drug exposure using single blood samples only
      provides short-term information and is highly subject to intra-individual
      pharmacokinetic variation. Drugs can accumulate in hair over a long period of
      time, so hair drug levels can provide drug exposure information over prolonged
      periods. We now report on a specific, sensitive, and reproducible liquid
      chromatography-tandem mass spectrometry method for measuring nevirapine (NVP), a
      widely used antiretroviral drug, levels in human hair using even a single short
      strand of hair. Hair samples are cut into small segments, and the drug is
      extracted in methanol/trifluoroacetic acid (v/v, 9:1) shaken at 37  degrees C in
      a water bath overnight, followed by liquid-liquid extraction under alkaline
      conditions. The extracted samples are then separated on a BDS-C(18) column with a
      mobile phase composed of 50% acetonitrile containing 0.15% acetic acid and 4 mM
      ammonium acetate with an isocratic elution for a total run time of 3 min and
      detected by triple quadrupole electrospray multiple reaction mode at
      precursor/product ion at 267.0 > 225.9 m/z. Deuterated nevirapine-d5 was used as
      an internal standard. This method was validated from 0.25 to 100 ng/mg using 2 mg
      hair samples. The accuracies for spiked NVP hair control samples were 98-106%
      with coefficients of variation (CV) less than 10%. The CV for incurred hair
      control samples was less than 7%. The extraction efficiency for incurred control
      hair samples was estimated at more than 95% by repeated extractions. This method
      has been successfully applied to analyze more than 1,000 hair samples from
      participants in a large ongoing cohort study of HIV-infected participants. We
      also showed that NVP in human hair can easily be detected in a single short
      strand of hair. This method will allow us to identify drug non-adherence using
      even a single strand of hair.

PMID- 21847532
TI  - The financial burden of stress urinary incontinence among women in the United
      States.
AB  - Stress urinary incontinence (SUI) is a common medical problem affecting 25% to
      50% of women in the United States. This article reviews the literature on the
      current systems- and population-based costs of management of SUI in women. A
      PubMed search was conducted to seek studies examining the cost of various
      management options. Both nonsurgical and surgical management can effectively
      improve symptoms of SUI at a wide spectrum of costs. Over $12 billion are spent
      annually, an amount that continues to grow. Patients pay out-of-pocket for 70% of
      conservative management, amounting to a significant individual financial burden.
      Systems-based cost of SUI management continues to rise with the aging population.
      Costs to both individuals and systems may be mitigated if more patients are
      treated with intent to cure and as surgical management transitions from inpatient
      to outpatient procedures.

PMID- 21847533
TI  - Molecular mechanisms of liver metastasis.
AB  - Colorectal cancer is the second most common cancer, and is the third leading
      cause of cancer-related death in Japan. The majority of these deaths is
      attributable to liver metastasis. Recent studies have provided increasing
      evidence that the chemokine-chemokine receptor system is a potential mechanism of
      tumor metastasis via multiple complementary actions: (a) by promoting cancer cell
      migration, invasion, survival and angiogenesis; and (b) by recruiting distal
      stromal cells (i.e., myeloid bone marrow-derived cells) to indirectly facilitate
      tumor invasion and metastasis. Here, we discuss recent preclinical and clinical
      data supporting the view that chemokine pathways are potential therapeutic
      targets for liver metastasis of colorectal cancer.

PMID- 21847534
TI  - Novel Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein: a
      biomarker of hepatocellular carcinoma recurrence in patients with low alpha
      fetoprotein concentrations.
AB  - BACKGROUND: Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP
      L3) is a specific marker used to detect hepatocellular carcinoma (HCC). However,
      its clinical utility is not sufficient in patients with low total AFP
      concentrations because of limitations in instrument sensitivity. Recent advances
      have led to the introduction of a highly sensitive AFP-L3% assay (sensitive AFP
      L3%), provided by a novel on-chip, liquid-phase binding assay. This cross
      sectional study was conducted to evaluate the clinical significance of the
      sensitive AFP-L3% in determining HCC recurrence in patients with low total AFP
      concentrations. METHODS: A total of 370 consecutive patients with HCC were
      screened within 1-3 months of locoregional treatment, and 215 of the 370 patients
      showed serum AFP <20 ng/ml. Total AFP, sensitive AFP-L3%, and des-gamma-carboxy
      prothrombin (DCP) were measured in those 215 patients and HCC recurrence was
      evaluated by radiological findings. Optimal cutoff values of the markers for
      detecting HCC recurrence were obtained on the basis of receiver operating
      characteristic (ROC) curve. RESULTS: The area under the ROC curve of the total
      AFP, sensitive AFP-L3%, and DCP in HCC patients with serum AFP <20 ng/ml were
      0.638, 0.724, and 0.779, respectively. The diagnostic accuracies of the total
      AFP, sensitive AFP-L3%, and DCP were 60.9% (cutoff value 5 ng/ml), 67.7% (cutoff
      value 7%), and 64.6% (cutoff value 40 ng/ml), respectively. CONCLUSIONS: The new
      sensitive AFP-L3% assay provides great utility in determining HCC recurrence in
      patients with low AFP concentrations. Further studies focusing on the
      combinatorial use of the markers (total AFP, sensitive AFP-L3%, and DCP) are
      required.

PMID- 21847535
TI  - Leptomeningeal carcinomatosis associated with gastric cancer.
AB  - BACKGROUND: Leptomeningeal carcinomatosis (LMC) is a rare but devastating
      complication of gastric cancer. METHODS: The subjects were 12 gastric cancer
      patients who were diagnosed as having LMC at the Shizuoka Cancer Center between
      October 2002 and March 2009. We conducted a retrospective survey of the medical
      records of the study subjects and collected data on the clinical features,
      treatment modalities employed/outcomes, and survival of the patients. RESULTS: Of
      the 12 patients, 9 (75%) were male, and the median age was 63 years.
      Histopathologically, the majority of the patients (83%) had diffuse-type
      adenocarcinoma. At the time of diagnosis of the LMC, the other major sites of
      metastasis were the peritoneum (75%) and lymph nodes (50%). The median duration
      from the diagnosis of gastric cancer to the diagnosis of LMC was 15.6 months.
      While the treatment strategy changed with time, intrathecal chemotherapy (n =
      10), followed by whole brain irradiation (n = 7) and subsequent ventriculo
      peritoneal shunt (n = 3) was performed in 10 of the patients. Improvement of
      neurological functions was observed in 6 of the 10 patients. The median overall
      survival time from the diagnosis of LMC in all the 12 patients was 60 days. One
      patient survived for a considerably long period of 532 days. CONCLUSIONS:
      Multidisciplinary treatment, including ventriculo-peritoneal shunt for LMC
      secondary to gastric cancer, may benefit selected patients, but further
      accumulation of clinical cases is necessary.

PMID- 21847536
TI  - The genetic analysis of the flp locus of Actinobacillus pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae, one of the most important porcine respiratory
      pathogens, exhibits tight adherence to cell surfaces. The Flp pilus, which is
      assembled by the proteins encoded by the flp (fimbrial low-molecular-weight
      protein) operon, may play an important role in the bacterial adherence. In this
      study, the flp operons of twelve A. pleuropneumoniae serotype reference strains
      were sequenced and analyzed. The phenotypic diversity of fimbriae was observed
      using transmission electron microscopy, and the adherence ability was tested
      against a porcine lung epithelial cell line. The complete flp operon was
      identified in the reference strains of serotypes 1, 4, 5, 7, 12, and 13,
      consisting of 14 genes (flp1-flp2-tadV-rcpCAB-tadZABCDEFG). Fimbriae were
      observed protruding from the bacterial cell surfaces of these strains. In
      contrast, the flp promoter was absent in serotypes 2, 3, 6, 9, and 11, and the
      flp1 gene was truncated in serotypes 10 and 15. No pilus was observed on the
      surfaces of these strains. The piliated strains have higher efficiency of
      adhesion than the pilus-negative strains. Our data demonstrated that the Flp pili
      are involved in A. pleuropneumoniae adherence. The genetic diversity of the flp
      operons among different strains may contribute, at least in part, to the
      variation in virulence of Actinobacillus pleuropneumoniae.

PMID- 21847537
TI  - Use of lithium in the treatment of bipolar disorder in late-life.
AB  - Lithium is the oldest and still one of the most frequently prescribed mood
      stabilizers in the treatment of bipolar disorder. Nonetheless, the evidence for
      lithium efficacy in older patients with bipolar disorder is almost entirely
      extrapolated from younger adult patients. Here we review the literature on
      lithium in older patients with bipolar disorder, concentrating on the past 3
      years. A definitive study demonstrating the efficacy and safety of lithium in
      older patients with bipolar disorder is still missing. However, several lines of
      indirect evidence suggest that it is beneficial and advantageous over other mood
      stabilizers in the acute and maintenance treatment of late-life bipolar disorder.
      In addition, lithium may have unique properties as a regenerative therapeutic
      with specific benefits in reducing the cognitive impairment and suicide rates
      associated with bipolar disorder across the adult lifespan. Aging-associated
      pharmacokinetic and pharmacodynamic changes as well as increased rates of medical
      comorbidities and polypharmacy predispose older patients to a higher risk of
      lithium toxicity. Careful monitoring and adjustment of lithium dosage is
      especially important in older adults to minimize the risk of toxicity.

PMID- 21847538
TI  - Gestational diabetes and risk of incident primary cancer: a large historical
      cohort study in Israel.
AB  - PURPOSE: Gestational diabetes mellitus (GDM), a state of glucose intolerance
      associated with pregnancy, is increasing in prevalence. Data regarding the cancer
      risk associated with GDM are sparse and limited to cancers of the breast and
      pancreas. This study was conducted to examine the risk of incident overall and
      site-specific malignancies associated with prior GDM in a historical cohort of
      women in a large health maintenance organization in Israel. METHODS: All pregnant
      women aged 15-50 years who underwent 50-g glucose challenge tests between 13
      March 1995 and 27 May 2009, without history of malignancy, diabetes, and
      infertility, were included. Clinical and demographic parameters at index date
      including age, socioeconomic level, BMI, and parity were collected. Diagnosis of
      gestational diabetes was based on the 100-g oral glucose tolerance test using
      Carpenter and Coustan criteria. Cancer diagnoses were obtained from the Israel
      Cancer Register through linkage data. RESULTS: Among the 185,315 women who had
      undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed
      with GDM. During a total follow-up period of 1.05 million person-years (mean =
      5.19 +/- 3.9, median = 4.3), 2,034 incident cases of cancer were identified. GDM
      was associated with a hazard ratio (HR) of 7.06 (95% CI: 1.69-29.45) for
      pancreatic cancer (nine cases) and a HR of 1.70 (95% CI: 0.97-2.99) for
      hematological malignancies (177 cases). The association between GDM and
      hematological malignancies was limited to women with 5 or more years of follow-up
      (HR = 4.53; 95% CI: 1.81-11.31). CONCLUSION: GDM is associated with an increased
      risk of pancreatic cancer and hematologic malignancies.

PMID- 21847539
TI  - Topical amitriptyline, ketamine, and lidocaine in neuropathic pain caused by
      radiation skin reaction: a pilot study.
AB  - PURPOSE: The purpose of this study is to assess the effect of topical
      amitriptyline, ketamine, and lidocaine (AKL) on alleviation of neuropathic pain
      from radiation dermatitis and the feasibility of a randomized trial. MATERIALS
      AND METHODS: Eligible subjects had radiation dermatitis with dry or moist
      desquamation with neuropathic pain and were intolerant or allergic to standard
      intervention. AKL was applied to painful sites three times a day daily until 2
      weeks post-radiotherapy. Subjects were monitored every 2-5 days during
      radiotherapy and at 2 and 6 weeks after completion of radiotherapy. The
      University of Washington Neuropathic Pain Scale was used to grade the neuropathic
      pain before and after use of the interventional gel. Compliance was assessed by
      asking subjects at each visit how frequently they were using the interventional
      gel. RESULTS: Over a 14-month period, 16 subjects met eligibility criteria.
      Eighty-two percent of subjects used the AKL as directed. Five subjects (32%)
      reported fatigue, and three subjects (19%) reported site irritation from the
      interventional gel. AKL was shown to significantly reduce (p < 0.05) pain
      intensity, sharpness, burning, sensitivity, itchiness, unpleasantness, deepness,
      and surfaceness levels on a short-term basis (i.e., between pre-treatment and 30
      min post-treatment). AKL was shown to significantly reduce (p < 0.05) burning
      levels on a long-term basis (i.e., between pre-treatment and 2 weeks post
      treatment). CONCLUSIONS: AKL was a safe intervention to use with minimal toxicity
      and good compliance. It significantly reduced several measures of neuropathic
      pain associated with radiation dermatitis. A larger-scale study would require
      recruitment from multiple centers.

PMID- 21847540
TI  - Small peripheral lung carcinomas with five-year post-surgical follow-up:
      assessment by semi-automated volumetric measurement of tumour size, CT value and
      growth rate on TSCT.
AB  - OBJECTIVES: To retrospectively assess the utility of semi-automated measurements
      by stratification of CT values of tumour size, CT value and doubling time (DT)
      using thin-section computed tomography (CT) images. The post-surgical outcomes of
      favourable and problematic tumours (more advanced p stage than IA, post-surgical
      recurrence or mortality from lung cancer) were compared using the measured
      values. The computed DTs were compared with manually measured values. METHODS:
      The study subjects comprised 85 patients (aged 33-80 years, 48 women, 37 men),
      followed-up for more than 5 years postoperatively, with 89 lung lesions,
      including 17 atypical adenomatous hyperplasias and 72 lung cancers. DTs were
      determined in 45 lesions. RESULTS: For problematic lesions, whole tumour diameter
      and density were >18 mm and >-400 HU, respectively. The respective values for the
      tumour core (with CT values of -350 to 150 HU) were >15 mm and >-70 HU. Analysis
      of tumour core DTs showed interval tumour progression even if little progress was
      seen by standard tumour volume DT (TVDT). CONCLUSION: Software-based volumetric
      measurements by stratification of CT values provide valuable information on
      tumour core and help estimate tumour aggressiveness and interval tumour
      progression better than standard manually measured 2D-VDTs.

PMID- 21847541
TI  - Magnetic resonance imaging in the preoperative assessment of patients with
      primary breast cancer: systematic review of diagnostic accuracy and meta
      analysis.
AB  - OBJECTIVES: To estimate the diagnostic accuracy of magnetic resonance imaging
      (MRI) in detecting additional lesions and contralateral cancer not identified
      using conventional imaging in primary breast cancer. METHODS: We have conducted a
      systematic review and meta-analyses to estimate diagnostic accuracy indices and
      the impact of MRI on surgical management. RESULTS: Fifty articles were included
      (n = 10,811 women). MRI detected additional disease in 20% of women and in the
      contralateral breast in 5.5%. The summary PPV of ipsilateral additional disease
      was 67% (95% CI 59-74%). For contralateral breast, the PPV was 37% (95% CI 27
      47%). For ipsilateral lesions, MRI devices >=1.5 Tesla (T) had higher PPV (75%,
      95% CI 64-83%) than MRI with <1.5 T (59%, 95% CI 53-71%). Similar results were
      found for contralateral cancer, PPV 40% (95% CI 29-53%) and 19% (95% CI 8-39%)
      for high- and low-field equipments, respectively. True positive MRI findings
      prompted conversion from wide local excision (WLE) to more extensive surgery in
      12.8% of women while in 6.3% this conversion was inappropriate. CONCLUSIONS: MRI
      shows high diagnostic accuracy, but MRI findings should be pathologically
      verified because of the high FP rate. Future research on this emerging technology
      should focus on patient outcome as the primary end-point.

PMID- 21847542
TI  - Targeted dual-energy single-source CT for characterisation of urinary calculi:
      experimental and clinical experience.
AB  - OBJECTIVE: To assess the accuracy of targeted dual-energy single-source multi
      detector CT (MDCT) for characterisation of urinary calculi. METHODS: For proof of
      principle, 71 ex-vivo calculi underwent single-source 256-slice MDCT. Low-dose CT
      was performed in 154 patients with suspected urinary calculi. In 104 patients
      with urinary calculi targeted dual-energy imaging within one breath-hold was
      added. 46 patients with sufficient material for infrared-spectroscopy were
      analysed. Potential anatomical misregistrations between 80- and 140-kV(p)-images
      and HU-values were measured. DEIs (dual-energy-indices) were compared with the
      standard of reference. Effective doses were calculated. RESULTS: In 26 of 46
      patients no misregistration was present. Mean deviations were 2.7 mm in the z
      axis (16 patients) and 4.3 mm in the axial plane (10 patients). The DEIs were
      0.018 +/- 0.016 for uric acid (UA), 0.035 +/- 0.015 for mixed UA and 0.102 +/-
      0.015 for calcified stones in-vitro and 0.017 +/- 0.002 for UA, 0.050 +/- 0.019
      for mixed UA and 0.122 +/- 0.024 for calcified calculi in-vivo. Significant
      differences were noted among calcium, mixed UA and UA stones (p < 0.05). For the
      low-dose examination mean effective dose was 3.11 mSv. Targed dual-energy
      resulted in an extra dose of 1.84 mSv (additional 59.1%). CONCLUSION: Targeted
      dual-energy imaging within one breath-hold is feasible for characterisation of
      urinary calculi using single-source MDCT allowing minimal anatomical discordance.

PMID- 21847543
TI  - Synovial tissue heterogeneity and peripheral blood biomarkers.
AB  - Rheumatoid arthritis is characterized by multiple pathobiological processes and
      heterogeneous clinical phenotypes. Not surprisingly, the inflamed synovium
      harbors an equally complex pathology. This includes variability in infiltrating
      and resident cell populations, spatial arrangements, and cell-cell interactions,
      as well as gene expression profiles. Remarkable progress in our understanding of
      the many facets of tissue heterogeneity has been facilitated by the increasing
      availability of patients' material and the development of advanced research
      technologies. The next challenge is to capitalize on the large amount of data
      generated to elucidate the specific pathogenic pathways disparately activated in
      different patients and/or different phases of the disease. When tissue pathology
      can be reliably explored through noninvasive circulating biomarkers, then the
      circle will be closed. We attempt to highlight key advances in the understanding
      of synovial tissue heterogeneity in rheumatoid arthritis and summarize novel
      perspectives in synovial biomarker discovery in relation to peripheral blood.

PMID- 21847544
TI  - LOX-1: a critical player in the genesis and progression of myocardial ischemia.
AB  - Myocardial ischemia is the most common cause of mortality and morbidity in the
      developed countries and rapidly becoming a common malady in the developing
      countries. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1),
      encoded by the OLR1 gene, is a scavenger receptor that plays a fundamental role
      in the genesis and progression of atherosclerosis and its complications. LOX-1
      has been identified as a major receptor for oxidized low-density lipoprotein (ox
      LDL) in endothelial cells, cardiomyocytes and fibroblast. In vitro and in vivo
      studies show that LOX-1 is upregulated during acute myocardial ischemia, and
      continues to be upregulated during chronic ischemia. Further, LOX-1 inhibition
      reduces ischemic myocardial injury and limits cardiac remodeling. LOX-1
      inhibition decreases oxidative stress and inflammatory response to injury
      resulting in limitation of ischemic injury. Molecular studies show that LOX-1
      inhibition reduces release of pro-inflammatory cytokines and expression of
      angiotensin II type 1 receptor via inhibition of redox-sensitive pathways. These
      alterations limit cardiomyocyte hypertrophy and collagen accumulation in the
      ischemic regions. These alterations in molecular signaling and physical
      alterations can result in improved cardiac function and better survival after
      ischemic myocardial injury.

PMID- 21847545
TI  - Comparison between quantitative assessment of bowel wall vascularization by
      contrast-enhanced ultrasound and results of histopathological scoring in
      ulcerative colitis.
AB  - PURPOSE: In ulcerative colitis (UC), endoscopic methods are preferred for
      assessment of extent and activity of disease. Due to the invasive nature of
      endoscopical examinations, replacement by other, reliable imaging procedures
      would be helpful. Contrast-enhanced ultrasound (CEUS) in combination with
      perfusion assessment using a specific quantification software might be such a new
      diagnostic tool. Thus, we compared the findings of CEUS with the results of
      endoscopically taken specimens applying a histopathological scoring system.
      METHODS: We prospectively evaluated 15 patients with proven UC undergoing
      endoscopy. CEUS was performed and the quantification software Qontrast(r) applied
      to obtain contrast-enhanced sonographic perfusion maps. Moreover, in each patient
      C-reactive protein (CRP) was measured and taken biopsies were assessed using an
      advanced scoring system. Four patients had to be excluded from final analysis.
      RESULTS: There was a trend to higher Peak (%) values with increasing histological
      inflammation. Furthermore, a strong negative correlation between the ratio TTP
      (s)/Peak (%) (Spearman's correlation r = -0.761, p < 0.01) was found. There was
      no significant relationship between CRP and histopathological scoring or CEUS
      parameters, respectively. CONCLUSION: Quantitative evaluation with CEUS,
      particularly the calculation of the ratio TTP (s)/Peak (%), provides a simple
      method for assessment of inflammatory activity in UC.

PMID- 21847546
TI  - HPV and precancerous lesions of anal canal in women: systematic review.
AB  - OBJECTIVE: The infection caused by human papillomavirus (HPV) in the anogenital
      area is considered the most common sexually transmitted infection in the world.
      Although anal cancer is relatively uncommon in the general population, there has
      been a significant increase in incidence in recent years. In this review, we
      focused on research on anal lesions in women. METHOD: Research on HPV and
      precancerous lesions of the anal canal was examined by a systematic literature
      review in the Cochrane Centre of Brazil, where 1,734 publications were identified
      in the databases Scielo Brazil, Pubmed, Lilac, Medline, and Old Medline, for the
      period 1966 to 2010. We selected two papers, published in 1994 and 2009, based on
      the inclusion-exclusion criteria. RESULTS: The first paper refers to the study of
      the anal canal in HIV-negative women with previous genital pathology and its
      relationship to the presence of HPV, and the other compares two groups of women
      who are HIV+ and HIV- and its relationship with anal disease and HPV. CONCLUSION:
      The existence of previous genital neoplasia associated with HPV promotes the
      development of anal lesions, especially in younger patients, and a poor immune
      status contributes to the appearance of this pathologic finding.

PMID- 21847547
TI  - Clinical features of headache patients with fibromyalgia comorbidity.
AB  - Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in
      migraine and tension-type headache. We aimed to update our previous results,
      considering a larger cohort of primary headache patients who came for the first
      time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients
      was screened. Frequency of FM in the main groups and types of primary headaches;
      discriminating factor for FM comorbidity derived from headache frequency and
      duration, age, anxiety, depression, headache disability, allodynia, pericranial
      tenderness, fatigue, quality of life and sleep, and probability of FM membership
      in groups; and types of primary headaches were assessed. FM was present in 174
      among a total of 889 included patients. It prevailed in the tension-type headache
      main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p
      < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep
      quality, and physical disability were the best discriminating variables for FM
      comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine
      and chronic tension-type headache had a higher probability of sharing the FM
      profile (Bonferroni test, p < 0.01). A phenotypic profile where headache
      frequency concurs with anxiety, sleep disturbance, and pericranial tenderness
      should be individuated to detect the development of diffuse pain in headache
      patients.

PMID- 21847548
TI  - Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the
      treatment of advanced gastric and esophageal cancer: a prospective,
      observational, single-institution experience.
AB  - The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5
      fluorouracil (5-FU) has emerged as an active treatment for advanced gastric
      cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991
      7, 2006) is associated with significant toxicity and therefore alternative
      schedules are needed. In the present study, patients with advanced gastric or
      esophageal cancer received Taxotere 35 mg/m(2) and cisplatin 25 mg/m(2) on day 1,
      followed by 5-FU 180 mg/m(2)/day as a 7-day prolonged infusion. Drugs were given
      weekly for 3 consecutive weeks followed by 1 week's rest. Cycles were repeated
      every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients
      (median age 63 years, range 40-78 years). The median number of cycles per patient
      was 4 (range 2-6). Nine partial responses were obtained, resulting in an overall
      response rate of 33% [95% confidence interval (CI) 16-51], a median time to
      progression of 6.4 months (95% CI 5.4-7.4), and a median overall survival of 10.7
      months (95% CI 6.6-14.8). Toxicity was mild; grade III-IV neutropenia was the
      most frequently observed side effect, in 9 administered cycles (8%); neutropenia
      was complicated by fever in 2 cycles. Other grade III-IV toxicities observed in
      >5% of patients were anemia and mucositis.

PMID- 21847549
TI  - The role of black carbon as a catalyst for environmental redox transformation.
AB  - Black carbon (BC) is an important class of geosorbents that control the fate and
      transport of organic pollutants in soil and sediment. We previously demonstrated
      a new role of BC as an electron transfer mediator in the abiotic reduction of
      nitroaromatic and nitramine compounds by Oh and Chiu (Environ Sci Technol 43:6983
      6988, 2009). We proposed that BC can catalyze the reduction of nitro compounds
      because it contains microscopic graphitic (graphene) domains, which facilitate
      both sorption and electron transfer. In this study, we assessed the ability of
      different types of BC--graphite, activated carbon, and diesel soot--to mediate
      the reduction of 2,4-dinitrotoluene (DNT) and 2,4-dibromophenol (DBP) by H(2)S.
      All three types of BC enhanced DNT and DBP reduction. H(2)S supported BC-mediated
      reduction, as was observed previously with a thiol reductant. The results suggest
      that BC may influence the fate of organic pollutants in reducing subsurface
      environments through redox transformation in addition to sorption.

PMID- 21847550
TI  - Platinum pollution in road dusts, roadside soils, and tree barks in Seoul, Korea.
AB  - This study presents the level of platinum in urban environment in and around
      Seoul, the capital city of Korea. Road dust, roadside soil, and tree bark samples
      were collected from the sites of various traffic volumes and from control sites
      in the suburbs. The above samples were analyzed for Pt by ICP-MS and other heavy
      metals by ICP-OES. Platinum levels in road dusts and roadside soils from Seoul
      were in the range of 3.8-444 ng/g (av. 115.0 ng/g) and 0.7-221 ng/g (av. 49.7
      ng/g), respectively, whereas those in the suburbs were in the range of 2.3-5.2
      ng/g (av. 3.9 ng/g) in road dusts and 0.4-5.1 ng/g (av. 2.4 ng/g) in roadside
      soils. The highest Pt levels in road dusts were found from major roads with high
      traffic volume. The remarkable difference in average Pt level between heavy
      traffic roads (av. 132.2 ng/g) and light traffic roads (av. 22.8 ng/g) reflects
      that an important source of Pt in roadside environment is automobile catalytic
      converter. High Pt level in road dust was found from the site of erratic stop
      start driving condition, for example, 178 ng/g Pt in road dust around a vehicle
      crossing gate. Platinum level in tree barks ranged from 0.9 to 4.5 ng/g, which
      indicates the existence of Pt-containing particulate matter in the atmosphere.
      Road dusts with high Pt level were enriched in traffic-related heavy metals.

PMID- 21847551
TI  - Osteolysis after rotator cuff repair with bioabsorbable anchors.
AB  - PURPOSE: The current study was designed to evaluate the rate of osteolysis and
      the clinical and functional outcomes in patients who underwent mini-open rotator
      cuff repairs using first generation bioabsorbable suture anchors. Our hypothesis
      was that patients with osteolysis noted on post-repair MRI would have an
      accompanying decrease in functional and clinical patient outcomes when compared
      with patients who did not have osteolysis evident on post-repair MRI. TYPE OF
      STUDY: Clinical retrospective study. METHODS: Between September 2000 and May
      2004, 76 patients were repaired using first generation Bio-Corkscrew suture
      anchors (Arthrex, Naples, FL). 30 patients were available for complete follow-up
      evaluation. The mean follow-up time was 36 months (range 24-58). Patients were
      assessed with the Constant-Murley Score, radiographs and magnetic resonance
      imaging (MRI). Post-operative strength was measured using an Isokinetic Cybex
      Dynamometer. 14 patients had osteolysis evident on MRI (Group A) while 16
      patients did not have osteolysis on MRI (Group B). RESULTS: In both groups, a
      total of 70 bio-anchors were used. 22 anchors showed osteolytic changes on MRI
      (Group A). Concerning ROM, there was no statistical difference in both groups.
      The Constant-Score was statistically not different in both groups A (92.4) and B
      (83.7). On MRI-scans, there were repair failures in both groups (A, 2 reruptures;
      B, 3 reruptures). CONCLUSIONS: Although, we found a high rate of osteolysis after
      rotator cuff repair with bioabsorbable anchors, these results did not change the
      clinical outcomes after rotator cuff repair. Recurrent tears were not
      significantly different in both groups and are comparable to rerupture rates in
      prior studies. More studies are needed to verify the effect of osteolysis over
      the long term.

PMID- 21847552
TI  - Primary sternal osteomyelitis due to Peptostreptococcus anaerobius.
AB  - Primary sternal osteomyelitis (PSO) is a rare syndrome. In adults, it usually
      occurs with underlying predisposing factors, such as immunodeficiency, or
      intravenous (IV) drug abuse. The infecting organism in these patients is usually
      Staphylococcus aureus or Pseudomonas aeruginosa. Peptostreptococcus species are
      Gram-positive anaerobic cocci and are part of the normal flora of human
      mucocutaneous surfaces. Peptostreptococcus infection can occur in all body sites,
      including the central nervous system, head, neck, chest, abdomen, pelvis, skin,
      bone, joint, and soft tissue. Here, we report on a 32-year-old previously healthy
      Chinese man who was diagnosed with PSO and P. anaerobius was yielded in the
      bacterial culture. He was treated empirically with antibiotics, but these failed.
      After additional limited surgical intervention with debridement, the PSO was
      cured.

PMID- 21847553
TI  - Giant psoas abscess caused by Streptococcus intermedius.

PMID- 21847554
TI  - Impact of the reduction of environmental and equipment contamination on
      vancomycin-resistant enterococcus rates.
AB  - More than 1,500 perirectal swab cultures and 552 environmental and equipment
      cultures were collected during the study period. Enterococcus faecium was the
      most frequent species isolated, being responsible for 71% of the positive
      cultures. Fifty infections were documented, with bloodstream infections (18, 36%)
      being the most frequent, followed by urinary tract infection (15, 30%). An
      educational intervention was given to 136 healthcare workers (HCWs), and a
      questionnaire regarding vancomycin-resistant enterococcus (VRE) transmission was
      also performed pre- and post-intervention. Overall, 858 opportunities of patient
      care were evaluated. The compliance with contact precautions did not improve;
      however, in general, the proportion of correct answers regarding VRE increased
      significantly when comparing pre- and post-intervention periods (p < 0.05). On
      the other hand, the proportion of environmental and equipment contaminated by VRE
      decreased significantly from pre- (23.2%) to post-intervention (8.2%) (p < 0.001)
      and was associated with a significant decrease in VRE infection from 7.7 to 1.9
      when comparing the pre- and post-intervention periods. The use of vancomycin
      (defined daily dose [DDD]) did not change significantly over the study period (p
      = 0.970), and the use of teicoplanin increased (p < 0.001). Seventy-six percent
      of E. faecium belong to type and subtype A by pulsed-field gel electrophoresis
      (PFGE). This predominant type was found in the environment and caused
      colonization and infection. In conclusion, the present study showed that
      reduction of the proportion of environmental and equipment contamination was
      associated with a decrease of colonization and infection due to VRE, and that the
      strategy to control VRE dissemination should be based on local problems.

PMID- 21847555
TI  - Feasibility and efficacy of extracorporeal shock-wave lithotripsy using a new
      modified lateral position for the treatment of renal stones in obese patients.
AB  - The aim of our study was to evaluate the efficacy and safety of ESWL using a
      modified lateral position in obese patients with renal stones. Nineteen obese
      patients with renal stones were enrolled (group A). The mean stone diameter was
      1.3 cm (0.7-1.9 cm). The mean BMI was 35.1 kg/m2 (31-41 kg/m2). Patients were
      placed in the lateral position, with the energy source facing their body
      posteriorly and the site where the stone was located in direct contact with the
      water cushion. Success rate (defined as the percentage of patients who were stone
      free or with insignificant fragments after 3 months), mean number of ESWL
      sessions, mean duration of ESWL session and complications were recorded. The
      results were compared with those of 17 obese patients (Group B) with similar
      baseline characteristics treated in the standard supine position. All ESWLs were
      performed using the Dornier lithotripter SII. Both success rate (68.4 vs. 64.7%
      for groups A and B, respectively) and mean number of sessions (2.2 vs. 2.6) did
      not differ significantly between the two groups (p = 0.5). Interestingly, the
      time required to complete ESWL was significantly shorter for group A patients (56
      min) compared to group B (73 min) (p = 0.001). No severe complications (including
      hematoma, pyelonephritis) were recorded. Our data indicate that ESWL in the
      modified lateral position for renal calculi in obese patients seems to be
      feasible and safe. In addition, it is faster than in the supine position since it
      overcomes technical difficulties. Further studies with a large number of patients
      are required to support our findings.

PMID- 21847556
TI  - Is the gravity effect of radiographic anatomic features enough to justify stone
      clearance or fragments retention following extracorporeal shock wave lithotripsy
      (SWL).
AB  - We determined whether the gravity effect of radiographic anatomic features on the
      preoperative urography (IVP) are enough to predict fragments clearance after
      shock wave lithotripsy (SWL). A Total of 282 patients with mean age 45.8 +/- 13.2
      years (189 male, 93 female), who underwent SWL due to renal calculi between
      October 2005 and August 2009 were enrolled. The mean calculi load was 155.72 +/-
      127.66 mm2. The patients were stratified into three groups: patients with pelvis
      calculi (group 1); patients with upper or middle pole calculi (group 2) and
      patients with lower pole calculi (group 3). Three angles on the pretreatment IVP
      were measured: the inner angle between the axis of the lower pole infundibular
      and ureteropelvic axis (angle I); the inner angle between the lower pole
      infundibular axis and main axis of pelvis-ureteropelvic (UP) junction point
      (angle II) and the inner angle between the lower pole infundibular axis and
      perpendicular line (angle III). Multivariate analysis was used to define the
      significant predictors of stone clearance. The overall success rate was 85.81%.
      All angles, sessions number, shock waves number and stone burden were significant
      predictors of success in patients in group 1. However, in group 2 only angle II
      and in group 3 angles I and II had significant effect on stone clearance.
      Radiographic anatomic features have significant role in determining the stone
      free rate following satisfactory fragmentation of renal stones with SWL. The
      measurement of infundibulopelvic angle in different manner helps to predict the
      stone-free status in patients with renal calculi located not only in lower pole,
      but also in renal pelvis and upper or middle pole. Gravity effect is not enough
      to justify the significant influence of the radiographic anatomic features on the
      stone clearance and fragments retention after SWL.

PMID- 21847557
TI  - Rescue of social behavior impairment by clozapine and alterations in the
      expression of neuronal receptors in a rat model of neurodevelopmental impairment
      induced by GRPR blockade.
AB  - We have previously shown that pharmacological blockade of the gastrin-releasing
      peptide receptor (GRPR) during the neonatal period in rats produces behavioral
      features of developmental neuropsychiatric disorders. Here, we show that social
      interaction deficits in this model are reversed by the atypical antipsychotic
      clozapine given in the adulthood. In addition, we analyzed the mRNA expression of
      three neuronal receptors potentially involved in the etiology of disorders of the
      autism spectrum. Rats were injected with the GRPR antagonist RC-3095 or saline
      (SAL) from postnatal days 1-10, and tested for social behavior and recognition
      memory in the adulthood. One hour prior to the behavioral testing, rats were
      given a systemic injection of clozapine or saline. The mRNA expression of the NR1
      subunit of the N-methyl-D-aspartate (NMDA) receptor, the epidermal growth factor
      receptor (EGFR), and GRPR was measured in the hippocampus and cortex of a
      separate set of rats given RC-3095 or SAL neonatally. Rats given neonatal RC-3095
      showed decreased social interaction and impaired object recognition memory.
      Clozapine rescued the social interaction impairment. Neonatal treatment with RC
      3095 also resulted in dose-dependent decreases in the expression of GRPR, NR1,
      and EGFR in the cortex, whereas all three receptor mRNAs were increased in the
      hippocampus in rats treated with the lower dose of RC-3095. The results
      contribute to further validate the novel rat model of neurodevelopmental
      disorders induced by GRPR blockade, and shows alterations in the expression of
      neuronal receptors in this model.

PMID- 21847558
TI  - Haemolysis induced by alpha-toxin from Staphylococcus aureus requires P2X
      receptor activation.
AB  - Recently, it was documented that alpha-haemolysin (HlyA) from Escherichia coli
      uses erythrocyte P2 receptors cause lysis. This finding was surprising as it
      appeared firmly established that HlyA-dependent pore formation per se is
      sufficient for full cell lysis. We discovered that HlyA induced a sequential
      process of shrinkage and swelling and that the final haemolysis is completely
      prevented by blockers of P2X receptors and pannexin channels. This finding has
      potential clinical relevance as it may offer specific pharmacological
      interference to ameliorate haemolysis inflicted by pore-forming bacterial toxins.
      In this context, it is essential to know whether this is specific to HlyA-induced
      cell damage or if other bacterial pore-forming toxins involve purinergic signals
      to orchestrate haemolysis. Here, we investigate if the haemolysis produced by
      alpha-toxin from Staphylococcus aureus involves P2 receptor activation. We
      observed that alpha-toxin-induced haemolysis is completely blocked by the
      unselective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'
      disulfonic acid. Moreover, several selective blockers of P2X(1) and P2X(7)
      ionotropic receptors abolished haemolysis in murine and equine erythrocytes.
      Inhibitors of pannexin channels partially reduced the alpha-toxin induced lysis.
      Thus, we conclude that alpha-toxin, similar to HlyA from E. coli produces cell
      damage by specific activation of a purinergic signalling cascade. These data
      indicate that pore-forming toxins in general require purinergic signalling to
      elicit their toxicity.

PMID- 21847560
TI  - Experience gained during the long term cultivation of keratinocytes for treatment
      of burns patients.
AB  - Both allogenic and autologous cultured skin cells have been used clinically on
      burn patients. In vitro cultivation of human keratinocytes has been routinely
      provided by the Central Tissue Bank in Bratislava since 1996, with an average
      annual production of around 7,000 cm(2). Keratinocytes have been cultivated using
      a version of the original by Rheinwald and Green (Cell 6:317-330, 1975)
      methodology which has been modified over time in our laboratory as we gained more
      experience with this serial passage system. We have observed that the growth of
      cultured keratinocytes depends on several important factors, including the timing
      of skin sample procurement, the method of skin sample procurement, the general
      condition of the patient, the quality and composition of the culture media and,
      to a lesser extent, the age of the patient. We aim to share our experience with
      other cell cultivation facilities.

PMID- 21847559
TI  - Involvement of phosphatidylinositol 5-phosphate in insulin-stimulated glucose
      uptake in the L6 myotube model of skeletal muscle.
AB  - The phosphoinositide phospholipid PtdIns5P has previously been implicated in
      insulin-stimulated translocation of the glucose transporter GLUT4 into the plasma
      membrane of adipocytes, but its potential role in glucose transport in muscle has
      not been explored. The involvement of PtdIns5P in insulin-stimulated glucose
      uptake was therefore investigated in myotubes of the skeletal muscle cell line
      L6. Stimulation with insulin produced a transient increase in PtdIns5P, which was
      abolished by the over-expression of the highly active PtdIns5P 4-kinase
      PIP4Kalpha. PIP4Kalpha over-expression also abolished both the enhanced glucose
      uptake and the robust peak of PtdIns(3,4,5)P (3) production stimulated by insulin
      in myotubes. Delivery of exogenous PtdIns5P into unstimulated myotubes increased
      Akt phosphorylation, promoted GLUT4 relocalisation from internal membrane to
      plasma membrane fractions and its association with plasma membrane lawns and also
      stimulated glucose uptake in a tyrosine kinase and phosphoinositide 3-kinase (PI
      3-kinase)-dependent fashion. Our results are consistent with a role for insulin
      stimulated PtdIns5P production in regulating glucose transport by promoting PI 3
      kinase signalling.

PMID- 21847561
TI  - Comparison of a new methodology for the assessment of 3D myocardial strain from
      volumetric ultrasound with 2D speckle tracking.
AB  - An alternative approach to extract 3D myocardial strain based on elastic
      registration of the ultrasound images (3DSE) was developed by our lab. The aim of
      the present study was to test its clinical performance by comparing strain values
      obtained by 3DSE with the ones obtained with 2D speckle tracking (2DST). Standard
      2D B-mode and volumetric datasets were acquired in 12 patients with coronary
      heart disease (CHD) and in 12 control subjects. Longitudinal (epsilon(LL)),
      circumferential (epsilon(CC)) and radial (epsilon(RR)) strain values were
      obtained from 2D datasets using commercially available 2DST software and from
      volumetric datasets using the 3DSE approach. 3DSE provided lower strain values
      than 2DST. With both approaches global epsilon(LL) and epsilon(CC) were
      significantly lower in patients with CHD than in controls. Global epsilon(LL) and
      epsilon(CC) correlated well between both methods (R = 0.83, R = 0.86,
      respectively), while segmental correlations were moderate [R = 0.63
      (epsilon(LL)), R = 0.41 (epsilon(CC))]. The highest differences in epsilon(LL)
      values obtained by the two methods and the highest number of erroneous
      epsilon(LL) with 3DSE were observed in the basal LV segments. This study shows
      that in real-life datasets our 3DSE method provides global and regional
      epsilon(LL) and epsilon(CC) values that are comparable with the ones obtained
      from 2DST, even though they are not interchangeable with each other. As only a
      single acquisition is required, 3D methods may offer advantages over the current
      2D techniques. However, the accuracy of the 3DSE can still be improved by solving
      the problems that appear with deformation estimation in the basal segments.

PMID- 21847562
TI  - Assessment of left atrial volume and function: a comparative study between
      echocardiography, magnetic resonance imaging and multi slice computed tomography.
AB  - Measurement of left atrial (LA) maximal volume (LA(max)) using two-dimensional
      transthoracic echocardiography (TTE) provides prognostic information in several
      cardiac diseases. However, the relationship between LA(max) and LA function is
      poorly understood and TTE is less well suited for measuring dynamic LA volume
      changes. Conversely, cardiac magnetic resonance imaging (CMR) and multi-slice
      computed tomography (MSCT) appears more appropriate for such measures. We sought
      to determine the relationship between LA size assessed with TTE and LA size and
      function assessed with CMR and MSCT. Fifty-four patients were examined 3 months
      post myocardial infarction with echocardiography, CMR and MSCT. Left atrial
      volumes and LA reservoir function were assessed by TTE. LA time-volume curves
      were determined and LA reservoir function (cyclic change and fractional change),
      passive emptying function (reservoir volume) and pump function (left atrial
      ejection fraction-LAEF) were derived using CMR and MSCT. Left atrial fractional
      change and left atrial ejection fraction (LAEF) determined with CMR and MSCT were
      unrelated to LA(max) enlargement by echocardiography (P = NS). There was an
      overall good agreement between CMR and MSCT, with a small to moderate bias in
      LA(max) (4.9 +/- 10.4 ml), CC (3.1 +/- 9.1 ml) and reservoir volume (3.4 +/- 9.1
      ml). TTE underestimates LA(max) with up to 32% compared with CMR and MSCT (P <
      0.001). Left atrial function assessed with MSCT and CMR as LA fractional change
      and LAEF is not significantly related to LA(max) measured by TTE. TTE
      systematically underestimated LA volumes, whereas there are good agreements
      between MSCT and CMR for volumetric and functional properties.

PMID- 21847563
TI  - A pallid paroxysmal event in children: it is vagal anoxic seizure, it is
      treatable, and it is not "epilepsy".

PMID- 21847564
TI  - The importance of endoscopic retrograde cholangiopancreatography in a young
      female with acute recurrent pancreatitis.

PMID- 21847565
TI  - Celiac disease screening assays for children younger than 3 years of age: the
      performance of three serological tests.
AB  - BACKGROUND AND AIMS: The optimum serological test for celiac disease (CD) in
      young children is not known. The objective of our study was to compare the
      performance of three serological tests (IgA + IgG DGP, IgA TTG, and IgA + IgG
      EMA) for children younger than 3 years of age. METHODS: We identified all
      subjects younger than 3 years of age (n = 6,074) that were tested for CD serology
      and included those with biopsy data. Patients were classified as group 1 (n =
      47): patients with confirmed CD or group 2 (n = 12): patients with normal biopsy
      findings. RESULTS: There was statistically significant difference between group 1
      and group 2 with regard to number of patients with positive IgA TTG (97.87% vs.
      50%, P < 0.001), IgA + IgG DGP (100% vs. 77.78%, P = 0.007), and IgA + IgG EMA
      (95.65% vs. 9.09%, P < 0.001). There was a significantly positive correlation
      between Marsh-Oberhuber score on the small duodenal biopsies and all tests.
      Analysis of sensitivity and specificity showed that manufacturer's levels had
      high sensitivity for all tests (IgA TTG 97%, IgA + IgG DGP 100%, IgA + IgG EMA
      96%), however specificity was low for IgA + IgG DGP (44%) and IgA TTG (50%) but
      not for IgA + IgG EMA (91%). CONCLUSIONS: For children younger than 3 years of
      age, IgA + IgG EMA is highly sensitive and specific. Use of IgA + IgG DGP or IgA
      TTG as a single serological marker is insufficient for definite diagnosis of CD
      in this age group. Based on our results, it might be reasonable to postpone the
      biopsy for asymptomatic children with negative EMA.

PMID- 21847566
TI  - Esophageal carcinoma in African Americans: a five-decade experience.
AB  - BACKGROUND: Esophageal cancer accounts for a considerable proportion of
      carcinomas of the upper gastrointestinal tract in African Americans. Our aim was
      to describe the epidemiology of esophageal squamous cell cancer (ESCC) and
      esophageal adenocarcinoma (EA) among African Americans in the last five decades.
      METHODS: A total of 601 records of patients with documented esophageal cancer
      between 1959 and 2007 at Howard University Hospital were reviewed. Demographic
      characteristics, risk factors, clinical stage and histological findings were
      reviewed. The change in prevalence of the disease and the interaction between
      main risk factors with tumor stage of the patients were assessed over the years
      of this study. RESULT: A total of 552 patients (91.8%) had ESCC while 49 patients
      (8.2%) had EA. The mean age at diagnosis was 60.1 and 60.6 years for ESCC and EA,
      respectively (P = 0.8). The peak incidence was in the 1980-1989 decade. Out of
      136 ESCC patients with TNM staging information, 130 (95.6%) were diagnosed in
      stage 2 and above. The majority (73%) of the ESCC were in the mid- and upper
      third of the esophagus and associated with smoking and alcohol exposure. The
      majority (81%) of the EA were in the mid- and lower third. The most common
      presenting symptoms were dysphagia (77.7%), and weight loss (31.9%). CONCLUSION:
      ESCC is the predominant esophageal cancer in African Americans and diagnosed in
      late stages, and its diagnosis in our institution has decreased since 1990. A
      combination of genetic factors, environmental influences (e.g., those related to
      diet), and the deleterious changes associated with smoking and alcohol
      consumption, and differences in tumor histology, are the obvious parameters that
      should be the focus of future studies, and early diagnosis at an earlier stage
      should be considered among blacks.

PMID- 21847567
TI  - Decreased colorectal cancer and adenoma risk in patients with microscopic
      colitis.
AB  - INTRODUCTION: Microscopic colitis is currently considered to harbor no increased
      risk for colorectal cancer, based on a few small studies with limited long-term
      follow-up. Our aim was to identify patients with microscopic colitis, and to
      compare long-term rates of colorectal cancer or adenoma to a control group of
      patients without microscopic colitis. METHODS: We reviewed the records of
      patients diagnosed with microscopic colitis, as identified by a hospital-based
      pathology database from January 2000 to August 2008. Clinical factors, including
      history of adenoma or adenocarcinoma, and all colonoscopy findings, were
      recorded. Age and gender-matched patients without microscopic colitis served as
      the control in a 1:1 fashion. RESULTS: A total of 647 patients (153 male: 494
      female) were identified with microscopic colitis (MC). Any history of colorectal
      cancer was detected in 1.92, 1.81, and 4.17% of patients with collagenous colitis
      (CC), lymphocytic colitis (LC), and controls, respectively (P = 0.095, P = 0.040,
      P = 0.015 for CC, LC, and all MC, respectively, comparing to controls). Overall,
      covariate-adjusted risk (odds ratio) of any history of colorectal cancer and
      colorectal adenoma in MC patients was 0.34 (95% confidence interval [CI] 0.16
      0.73, P = 0.006) and 0.52 (95% CI 0.50-0.76, P < 0.0001), respectively. The mean
      duration of follow-up was 4.63 years, with 147/647 (22.7%) of patients with
      clinical follow-up >7 years. CONCLUSIONS: In this case-control study involving a
      large retrospective cohort, microscopic colitis is negatively associated with the
      risk for colorectal cancer and adenoma. Further studies are required to determine
      a temporal relationship between microscopic colitis and the future development of
      colorectal neoplasia.

PMID- 21847568
TI  - First report of a secondary aortojejunal fistula visualized by small bowel
      capsule endoscopy.

PMID- 21847569
TI  - Effects of a novel mGlu2/3 receptor agonist prodrug, LY2140023 monohydrate, on
      central monoamine turnover as determined in human and rat cerebrospinal fluid.
AB  - RATIONALE: Accumulating evidence suggests that the primary symptoms of
      schizophrenia may be associated with altered central glutamate transmission.
      LY2140023 monohydrate is the methionine prodrug of the selective mGlu(2/3)
      receptor agonist LY404039 and is currently being assessed for the treatment of
      schizophrenia. OBJECTIVE: The objective of this study was to evaluate the central
      pharmacological activity of LY2140023 monohydrate in preclinical and clinical
      studies. METHODS: Effects on neurotransmitter/metabolite concentrations were
      assessed in male rats following single oral doses of LY2140023 monohydrate
      (microdiasylates from the prefrontal cortex), single intraperitoneal injection of
      LY404039 [cerebrospinal fluid (CSF)], or LY2140023 monohydrate dosed once daily
      for 7 days (CSF). A clinical study in 16 healthy subjects assessed the effects of
      LY2140023 monohydrate 40 mg orally twice daily for 14 days in lumbar CSF.
      RESULTS: Rat studies: Acute dosing with LY2140023 monohydrate resulted in
      significant dose-dependent increases in extracellular concentrations of
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), but not 5
      hydroxyindoleacetic acid (5-HIAA), in the prefrontal cortex. LY2140023
      monohydrate dosing for 7 days elevated the concentrations of HVA in CSF, while
      acutely dosed LY404039 increased the concentrations of DOPAC, HVA, and methoxy
      hydroxyphenylglycol (MHPG), but not 5-HIAA. Clinical study: Significant increases
      were seen for DOPAC, HVA, 5-HIAA, and MHPG in the CSF of subjects receiving
      LY2140023 monohydrate, but not placebo. CONCLUSIONS: LY2140023 monohydrate and/or
      LY404039 dosing potently affected dopamine turnover and also significantly
      affected serotonin turnover in the human and rat central nervous systems. The
      measurement of biogenic amine metabolites such as DOPAC and HVA may serve as
      useful biomarkers of LY2140023 monohydrate and/or LY404039 central
      pharmacodynamic activity.

PMID- 21847570
TI  - Beta receptor-mediated modulation of the late positive potential in humans.
AB  - RATIONALE: Electrophysiological studies have identified a scalp potential, the
      late positive potential (LPP), which is modulated by the emotional intensity of
      observed stimuli. Previous work has shown that the LPP reflects the modulation of
      activity in extrastriate visual cortical structures, but little is known about
      the source of that modulation. OBJECTIVES: The present study investigated whether
      beta-adrenergic receptors are involved in the generation of the LPP. METHODS: We
      used a genetic individual differences approach (experiment 1) and a
      pharmacological manipulation (experiment 2) to test the hypothesis that the LPP
      is modulated by the activation of beta-adrenergic receptors. RESULTS: In
      experiment 1, we found that LPP amplitude depends on allelic variation in the
      beta1-receptor gene polymorphism. In experiment 2, we found that LPP amplitude
      was modulated by the beta-blocker propranolol in a direction dependent on
      subjects' level of trait anxiety: In participants with lower trait anxiety,
      propranolol led to a (nonsignificant) decrease in the LPP modulation; in
      participants with higher trait anxiety, propranolol increased the emotion-related
      LPP modulation. CONCLUSIONS: These results provide initial support for the
      hypothesis that the LPP reflects the downstream effects, in visual cortical
      areas, of beta-receptor-mediated activation of the amygdala.

PMID- 21847571
TI  - Familial pancreatic cancer and hereditary syndromes: screening strategy for high
      risk individuals.
AB  - Globally, and almost evenly across nations, a familial disposition can be found
      in 4-10% of patients with pancreatic cancer (PC). A family history of PC is a
      risk for this disease and the risk level changes in correlation with the number
      of affected relatives. Several hereditary syndromes with potential germline
      mutation also have a high risk for PC; however, little is yet known regarding the
      genes responsible for familial pancreatic cancer (FPC). Characteristics of FPC
      cases are similar to those of other familial tumors, including younger onset than
      in sporadic cases and an ethnic difference (Ashkenazi Jewish > other Caucasian).
      Other risks resemble those of sporadic cases and include smoking and diabetes
      mellitus. People with several genetic syndromes, including Peutz-Jeghers
      syndrome, hereditary pancreatitis, breast-ovarian cancer syndrome, hereditary
      nonpolyposis colorectal cancer, and familial adenomatous polyposis also have an
      increased risk of PC. In many countries, but not yet in Japan, screening of these
      high-risk individuals is now ongoing for the detection of early PC under
      established familial pancreatic cancer registries. In addition to the ordinary
      risk factors, such as smoking, diabetes, pancreatitis, cysts, duct ectasia, and
      intraductal papillary mucinous neoplasm (IPMN), individuals with a family history
      of PC and hereditary syndromes are expected to be entered into the screening
      protocol.

PMID- 21847572
TI  - A comparison of cabergoline and bromocriptine on the risk of valvular heart
      disease in patients with prolactinomas.
AB  - Therapy with dopamine agonists has been associated with valvular heart disease
      (VHD) in Parkinson's disease, raising concern about the safety of these drugs. In
      hyperprolactinemic patients, the studies have mainly focused on the cardiac
      effects of cabergoline (CBG), with little information on bromocriptine (BRC). The
      aim of the present study was to evaluate the prevalence of VHD in patients with
      prolactinomas treated with CBG and BRC. The CBG group consisted of 51 patients
      (37 female; age 42.3 +/- 13.5 years) who had been taking CBG for at least 1 year
      (mean 37.8 +/- 21.3 months; cumulative doses 16-1,286.8 mg). The BRC group
      consisted of 19 patients (14 female; age 41.8 +/- 11.5 years) who were on BRC for
      at least 1 year (mean 54.8 +/- 30.2 months; cumulative doses 4,687.5-23,478.8
      mg). The controls (CTR) were 59 healthy subjects matched for age, sex, and
      prevalence of arterial hypertension. Participants were subjected to transthoracic
      echocardiography and the valvular regurgitation was graduated as absent (grade
      0), trace (1), mild (2), moderate (3) or severe (4). Compared to CTR, trace
      mitral (Mi) regurgitation (49% vs. 27.1%; P = 0.02), trace tricuspid (Tri)
      regurgitation (45.1% vs. 20.3%; P = 0.0003) and mild Tri regurgitation (7.8% vs.
      0%; P = 0.0003) were more prevalent with CBG, while trace Tri regurgitation
      (73.7% vs. 20.3%; P = 0.0004) were more prevalent with BRC. Mitral tenting area
      was significantly higher in CBG than in BRC and CTR. None of the valvar
      abnormalities was associated with symptoms. In conclusion, patients with
      prolactinomas treated with either CBG or BRC showed higher prevalence of trace
      and mild Tri or Mi regurgitation, but these findings were not clinically
      significant.

PMID- 21847573
TI  - Genomic sequencing and analysis of Chilli ringspot virus, a novel potyvirus.
AB  - Chilli ringspot virus (ChiRSV), a novel potyvirus, was recently found in Hainan,
      China with high prevalence. The genomic sequence of the ChiRSV-HN/14 isolate was
      determined by sequencing overlapping cDNA segments generated by reverse
      transcription polymerase chain reaction with degenerate and/or specific primers.
      ChiRSV genome (GenBank Acc. no. JN008909) comprised of 9,571 nucleotides (nt)
      excluding the 3'-terminal poly (A) tail and contained a large open reading frame
      of 9,240 nt encoding a large polyprotein of 3,079 amino acids with predicted Mr
      of 349.1 kDa. A small, overlapping PIPO coding region was also found to span from
      nt 2,913 to 3,095, with a capacity to encode a peptide of 60 amino acids. ChiRSV
      shares sequence identities of only 48.5-65.4 and 42.9-68.7% with closely related
      potyviruses at the nucleotide and the amino acid levels, respectively.
      Phylogenetic analysis of the genomic sequences provided further evidence that
      ChiRSV is a distinct species of the Potyvirus genus. ChiRSV-HN/14 is most closely
      related to Tobacco vein banding mosaic virus and two other pepper-infecting
      potyviruses.

PMID- 21847574
TI  - Does electrical stimulation enhance post-exercise performance recovery?
AB  - Elite sport requires high-volume and high-intensity training that inevitably
      induces neuromuscular fatigue detrimental for physical performance. Improving
      recovery processes is, therefore, fundamental and to this, a wide variety of
      recovery modalities could be proposed. Among them, neuromuscular electrical
      stimulation is largely adopted particularly by endurance-type and team sport
      athletes. This type of solicitation, when used with low stimulation frequencies,
      induces contractions of short duration and low intensity comparable to active
      recovery. This might be of interest to favour muscle blood flow and therefore
      metabolites washout to accelerate recovery kinetics during and after fatiguing
      exercises, training sessions or competition. However, although electrical
      stimulation is often used for recovery, limited evidence exists regarding its
      effects for an improvement of most physiological variables or reduced subjective
      rating of muscle soreness. Therefore, the main aim of this brief review is to
      present recent results from the literature to clarify the effectiveness of
      electrical stimulation as a recovery modality.

PMID- 21847575
TI  - A polymerase chain reaction-based methodology to detect gene doping.
AB  - The non-therapeutic use of genes to enhance athletic performance (gene doping) is
      a novel threat to the world of sports. Skeletal muscle is a prime target of gene
      therapy and we asked whether we can develop a test system to produce and detect
      gene doping. Towards this end, we introduced a plasmid (pCMV-FAK, 3.8 kb, 50 MUg)
      for constitutive expression of the chicken homologue for the regulator of muscle
      growth, focal adhesion kinase (FAK), via gene electro transfer in the anti
      gravitational muscle, m. soleus, or gastrocnemius medialis of rats. Activation of
      hypertrophy signalling was monitored by assessing the ribosomal kinase p70S6K and
      muscle fibre cross section. Detectability of the introduced plasmid was monitored
      with polymerase chain reaction in deoxyribonucleic acids (DNA) from transfected
      muscle and serum. Muscle transfection with pCMV-FAK elevated FAK expression 7-
      and 73-fold, respectively, and increased mean cross section by 52 and 16% in
      targeted muscle fibres of soleus and gastrocnemius muscle 7 days after gene
      electro transfer. Concomitantly p70S6K content was increased in transfected
      soleus muscle (+110%). Detection of the exogenous plasmid sequence was possible
      in DNA and cDNA of muscle until 7 days after transfection, but not in serum
      except close to the site of plasmid deposition, 1 h after injection and surgery.
      The findings suggest that the reliable detection of gene doping in the immoral
      athlete is not possible unless a change in the current practice of tissue
      sampling is applied involving the collection of muscle biopsy close to the site
      of gene injection.

PMID- 21847576
TI  - Skeletal muscle quality assessed from echo intensity is associated with muscle
      strength of middle-aged and elderly persons.
AB  - Enhanced echo intensity (EI) on an ultrasound image of skeletal muscle indicates
      changes in muscle quality, including increases in intramuscular fibrous and
      adipose tissues. However, it is not known whether muscle quality assessed from
      the EI of computer-aided gray-scale analysis of an ultrasound image is associated
      with the muscle strength or body composition of a subject. The objectives of this
      study were to investigate whether muscle quality assessed from EI measured using
      gray-scale analysis is associated with muscle strength independently of age or
      muscle thickness (MT), and to examine the relationship between muscle EI and body
      composition. Ninety-two healthy women with a mean age of 70.4 +/- 5.5 years
      (range, 51-87 years) dwelling in Kyoto, Japan, participated in the study. The MT,
      subcutaneous fat thickness (FT), and EI of the quadriceps femoris on the right
      extremity were assessed from transverse ultrasound images. Knee extensor
      isometric strength was used as a measure of the quadriceps femoris muscle
      strength. EI was significantly correlated with quadriceps strength independently
      of age or MT, and stepwise regression analysis revealed that MT and EI were
      independently associated with quadriceps strength. Importantly, EI showed no
      significant correlations with FT, percentage of body fat (%BF), or body mass
      index (BMI), while FT, BMI, and %BF did not significantly influence muscle
      strength. These data suggest that muscle quantity (i.e., MT) and muscle quality
      assessed from EI measured using computer-aided gray-scale analysis independently
      contribute to muscle strength in middle-aged and elderly persons.

PMID- 21847577
TI  - Clinical and histopathological features and immunoreactivity of human choroidal
      and ciliary melanomas as prognostic factors for metastasis and death.
AB  - PURPOSES: To determine the relationship between immunohistochemical reactivity to
      osteopontin, vimentin, keratin 8/18, LZTS1, and beta-catenin and clinical and
      histopathological prognostic factors for metastasis and death in archival
      specimens of primary uveal melanomas, and the prognostic value of the evaluated
      study variables for death from metastasis. METHODS: Retrospective analysis of
      clinical records and formalin-fixed, paraffin-embedded slides of primary uveal
      melanomas treated by enucleation during May 1 1999, through June 30 2009.
      Immunofluorescent staining of each tumor was assessed on newly prepared
      histologic slides after the application of antibodies directed against five
      biomarkers associated with unfavorable prognosis in uveal melanoma. RESULTS:
      After exclusions, our study group consisted of 82 cases. Immunofluorescence was
      observed in 40.2% of specimens evaluated for keratin, 50.0% evaluated for
      osteopontin, 26.8% evaluated for beta-catenin, 65.9% evaluated for vimentin, and
      70.7% evaluated for LZTS1. Through available follow-up, 27 patients (32.9%) were
      dead of confirmed or suspected metastatic uveal melanoma. None of the patients
      whose tumor exhibited strong immunoreactivity to beta-catenin died of metastasis.
      In contrast, patients whose tumor exhibited immunoreactivity of any intensity to
      LZTS1 were more likely to develop metastasis. In multivariate Cox proportional
      hazards modeling, a composite variable that took into account the immunostaining
      for both beta-catenin and LZTS1 had a statistically significant relationship with
      patient's survival time. CONCLUSIONS: Our study suggests that conventional
      clinical and histopathological prognostic factors, and immunoexpression of beta
      catenin and LZTS1 combined may allow better prognostication of metastasis than
      clinical and histomorphological factors alone.

PMID- 21847578
TI  - Neural stem/progenitor cells circulating in peripheral blood of patients with
      neovascular form of AMD: a novel view on pathophysiology.
AB  - BACKGROUND: The neovascular form of age-related macular degeneration (AMD)
      manifested with choroidal neovascularization (CNV) is one of the leading causes
      of rapid and irreversible visual loss. Recent reports suggest that bone marrow
      derived stem/progenitor cells (SPCs) play a crucial role in the development and
      progression of the disease. The purpose of this study was to investigate whether
      or not undifferentiated non-haematopoietic stem cells, including those capable of
      differentiating into neural phenotypes, play a role in the pathological state of
      CNV formation. METHODS: Peripheral blood samples were collected from 46 patients
      diagnosed with CNV and from 46 controls. The CXCR4(+)Lin(-)CD45(-) stem cells
      were counted and analysed by flow cytometry. Using qRT-PCR and
      immunocytofluorescence, the expression of early neural and glial cell markers
      (beta-III-tubulin, nestin, and glial fibrillary acidic protein) in the sorted
      cells was analysed, and correlated with plasma concentrations of stromal cell
      derived factor 1 (SDF-1) (enzyme-linked immunosorbent assay), which is a pivotal
      chemokine that regulates the trafficking of SPCs. RESULTS: We found that the
      number of circulating CXCR4(+)Lin(-)CD45(-) cells did not differ in patients with
      active CNV as compared to the controls. However, we noticed significant
      intracellular overexpression of beta-III-tubulin in the cells derived from AMD
      patients. Moreover, we observed significantly lower SDF-1 plasma levels in
      neovascular AMD patients compared to healthy individuals. CONCLUSIONS: Our
      findings suggest that neural progenitor cells, together with low SDF-1
      concentrations, may play a considerable role in the process of AMD progression.
      Further investigations aimed at the precise elucidation of these issues may help
      with the future development of effective prevention against, and the treatment
      of, this disease.

PMID- 21847579
TI  - [Infectious enteritis].
AB  - Infectious diarrhea belongs to the most frequent infections worldwide and can be
      elicited by a wide array of microbial pathogens. In developed countries
      transmission occurs much more frequently from contaminated food as compared to
      direct person-to-person contact, except for enteric viruses which can also be
      transmitted by aerosol formation after vomiting. In Germany, more than 90% of
      cases are caused by the four pathogens Norovirus, Rotavirus, Campylobacter and
      Salmonella. Therapy of infectious diarrhea is mainly supportive. In cases with a
      severe or prolonged course, signs of inflammation, bloody stool,
      immunosuppression, comorbidity and in suspected outbreaks, fecal microbial
      analysis should be performed and a specific therapy should be considered if
      indicated.

PMID- 21847580
TI  - PCSK9 siRNA inhibits HUVEC apoptosis induced by ox-LDL via Bcl/Bax-caspase9
      caspase3 pathway.
AB  - This paper investigated the effects of ox-LDL on PCSK9, and the molecular
      mechanisms of PCSK9 siRNA-inhibited apoptosis induced by ox-LDL in human
      umbilical vein endothelial cells (HUVECs), to clarify the role of PCSK9 in
      atherosclerogenesis. HUVECs were incubated with ox-LDL for 24 h. The apoptosis
      was observed by Hoechst 33258 staining. The expression of PCSK9, LOX-1 mRNAs and
      proteins was detected by RT-PCR, western blot, respectively. The PCSK9 siRNAs
      labeled with fluorescence were transfected into HUVECs by Lipofectamine 2000.
      After transfection for 24 h, cells were treated with ox-LDL for 24 h, HUVECs
      apoptosis transfected siRNA was detected by Hoechst 33258 staining and flow
      cytometer. The expression of Bcl-2, Bax, caspase3, 8, 9 was detected by western
      blot. The activity of caspase3, 9 was detected by kits. Our results showed that
      apoptosis of HUVECs and the expressions of PCSK9 and LOX-1 were upregulated
      secondary to induction by ox-LDL in a concentration-dependent manner. However, ox
      LDL-induced HUVEC apoptosis and PCSK9 expression, but not LOX-1 expression, were
      significantly reduced by PCSK9 siRNA. These results demonstrate a linkage between
      HUVEC apoptosis and PCSK9 expression. Furthermore, we detected the possible
      pathway involved in apoptotic regulation by PCSK9 siRNA; our results showed that
      the expression of Bcl-2 decreased, whereas that of Bax increased. In addition, ox
      LDL enhanced the activity of caspase9 and then caspase3. Pretreatment of HUVECs
      with PCSK9 siRNA blocked these effects of ox-LDL. These findings suggest that ox
      LDL-induced HUVECs apoptosis could be inhibited by PCSK9 siRNA, in which Bcl/Bax
      caspase9-caspase3 pathway maybe was involved through reducing the Bcl-2/Bax ratio
      and inhibited the activation of both caspase9 and 3.

PMID- 21847581
TI  - Phosphatidylinositol 3-kinase inhibitor suppresses inducible nitric oxide
      synthase expression in bronchiole epithelial cells in asthmatic rats.
AB  - Inducible nitric oxide synthase (iNOS) is known to produce nitric oxide (NO),
      which is a main contributor to asthmatic airway inflammation. Recent studies have
      shown that phosphatidylinositol 3-kinase (PI3K) is ubiquitously expressed in
      airway epithelial cells and its inhibition could relieve airway inflammation and
      hyperresponsiveness. This study aimed to explore the interaction of PI3K and NO
      signaling in allergic asthma. We investigated the effects of PI3K inhibitor
      wortmannin on iNOS expression in bronchiole epithelial cells and NO, IL-4 and IFN
      gamma levels in lung tissues of asthmatic rat model, which was prepared by 10%
      OVA solution sensitization and 1% OVA aerosol challenge. Our results showed that
      the ratio of eosinophils to total cells in BALF, PI3K activity, NO and IL-4
      levels in lung tissues was increased after OVA sensitization and challenge, but
      then was attenuated by the administration of wortmannin. In contrast, IFN-gamma
      level in lung tissues was decreased after OVA sensitization and challenge and
      increased after the administration of wortmannin. The expression of iNOS protein
      in bronchiole epithelial cells, iNOS mRNA level and iNOS activity in lung tissues
      was markedly upregulated after OVA sensitization and challenge, but the
      upregulation was significantly antagonized by wortmannin. Taken together, these
      data provide evidence that PI3K functions upstream to modulate iNOS/NO signaling,
      which then promotes the development of airway inflammation in asthmatic animal
      model. PI3K inhibitor wortmannin could lead to reduced iNOS expression and NO
      production, therefore inhibiting airway inflammatory responses.

PMID- 21847582
TI  - Altered endocannabinoid signalling after a high-fat diet in Apoe(-/-) mice:
      relevance to adipose tissue inflammation, hepatic steatosis and insulin
      resistance.
AB  - AIMS/HYPOTHESIS: Apolipoprotein E (ApoE) deficiency is associated with reduced
      fat accumulation in white adipose tissue (WAT) and high liver triacylglycerol
      content. Elevated levels of endocannabinoids and cannabinoid receptor type 1
      (CB(1)) receptors in the liver and in epididymal vs subcutaneous WAT are
      associated with fatty liver, visceral adipose tissue, inflammatory markers and
      insulin resistance. METHODS: We investigated, in Apoe (-/-) and wild-type (WT)
      mice, the effect of a high-fat diet (HFD) on: (1) subcutaneous and epididymal WAT
      accumulation, liver triacylglycerols, phospholipid-esterified fatty acids,
      inflammatory markers in WAT and liver, and insulin resistance; and (2)
      endocannabinoid levels, and the gene expression levels of the Cb ( 1 ) receptor
      and endocannabinoid metabolic enzymes in liver and WAT. RESULTS: After a 16 week
      HFD, Apoe (-/-) mice exhibited lower body weight, WAT accumulation and fasting
      leptin, glucose and insulin levels, and higher hepatic steatosis, than WT mice.
      Glucose clearance and insulin-mediated glucose disposal following the HFD were
      slower in WT than Apoe (-/-) mice, which exhibited higher levels of mRNA encoding
      inflammatory markers (tumour necrosis factor-alpha [TNF-alpha], monocyte
      chemoattractant protein-1 [MCP-1], cluster of differentiation 68 [CD68] and EGF
      like module-containing mucin-like hormone receptor-like 1 [EMR1]) in the liver,
      but lower levels in epididymal WAT. HFD-induced elevation of endocannabinoid
      levels in the liver or epididymal WAT was higher or lower, respectively, in Apoe
      (-/-) mice, whereas HFD-induced decrease of subcutaneous WAT endocannabinoid and
      CB(1) receptor levels was significantly less marked. Alterations in
      endocannabinoid levels reflected changes in endocannabinoid catabolic enzymes in
      WAT, or the availability of phospholipid precursors in the liver.
      CONCLUSIONS/INTERPRETATION: Liver and adipose tissue endocannabinoid tone
      following an HFD is altered on Apoe deletion and strongly associated with
      inflammation, insulin resistance and hepatic steatosis, or lack thereof.

PMID- 21847583
TI  - LDL from obese patients with the metabolic syndrome show increased lipid
      peroxidation and activate platelets.
AB  - AIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients
      with the metabolic syndrome and compared it with that in LDL from type 2 diabetic
      patients or control volunteers. It also determined the effect on platelets of LDL
      from the three groups. METHODS: The profiles of lipids, fatty acids and fatty
      acid oxidation products were determined in LDL isolated from plasma of patients
      with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10
      per group). The effects of LDL from the participant groups on the platelet
      arachidonic acid signalling cascade and aggregation were investigated. RESULTS:
      Compared with LDL from control volunteers, LDL from obese metabolic syndrome and
      type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and
      lower ethanolamine plasmalogen levels. Proportions of linoleic acid were
      decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient
      groups. Among the markers of lipid peroxidation, oxidation products of linoleic
      acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59%
      and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic
      patients. LDL from metabolic syndrome and type 2 diabetic patients were equally
      potent in activating the platelet arachidonic acid signalling cascade through
      increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic
      phospholipase A(2), and through increased thromboxane B(2) formation. LDL from
      patients with the metabolic syndrome and type 2 diabetes potentiated platelet
      aggregation by threefold and 3.5-fold respectively, whereas control LDL had no
      activating effects on platelets. CONCLUSIONS/INTERPRETATION: The metabolic
      syndrome in obese patients, without or with diabetes, is associated with
      increased oxidative stress in LDL, which triggers platelet activation.

PMID- 21847585
TI  - Association of kisspeptin-10 levels with abortus imminens: a preliminary study.
AB  - PURPOSE: To investigate the association between kisspeptin 10 (Kp-10) levels and
      early pregnancy bleeding and perinatal outcome. METHODS: A total of 20 pregnant
      women with the complaint of vaginal bleeding during 7-18 gestational weeks and 20
      healthy gestational week matched pregnant women were included in the study.
      Maternal plasma Kp-10 levels were measured with the enzyme immunoassay method.
      Adverse pregnancy outcomes like intrauterine growth restriction, preterm
      delivery, preeclampsia and low birth weight were evaluated in both groups.
      RESULTS: Maternal plasma Kp-10 levels (p = 0.01) and birth weight (p = 0.06) were
      found to be lower in women with bleeding. Intrauterine growth restriction,
      preterm delivery and intrauterine exitus were noted more commonly in women with
      bleeding (10 vs. 0%, 25 vs. 15% and 20 vs. 0%, p = 0.08). Preeclampsia were
      developed in 5% of both groups. Kp-10 levels showed positive correlation with
      gestational week (p = 0.02) and ALT levels (p = 0.02). CONCLUSION: [corrected] Kp
      10 levels were found lower in women with early pregnancy bleeding.

PMID- 21847584
TI  - Increased neuronal nitric oxide synthase dimerisation is involved in rat and
      human pancreatic beta cell hyperactivity in obesity.
AB  - AIMS/HYPOTHESIS: Pancreatic beta cell hyperactivity is known to occur in obesity,
      particularly in insulin-resistant states. Our aim was to investigate whether
      changes in neuronal nitric oxide synthase (nNOS) function affect beta cell
      compensation in two relevant models: the Zucker fa/fa rats and pancreatic islets
      from obese humans. METHODS: Glucose-induced insulin response was evaluated in the
      isolated perfused rat pancreas and in human pancreatic islets from obese
      individuals. Expression of nNOS (also known as NOS1) and subcellular localisation
      of nNOS were studied by quantitative RT-PCR, immunoblotting, immunofluorescence
      and electron microscopy. RESULTS: Pancreatic beta cells from Zucker fa/fa rats
      and obese individuals were found to be hyper-responsive to glucose.
      Pharmacological blockade of nNOS was unable to modify beta cell response to
      glucose in fa/fa rats and in islets from obese individuals, suggesting an
      abnormal control of insulin secretion by the enzyme. In both cases, nNOS activity
      in islet cell extracts remained unchanged, despite a drastic increase in nNOS
      protein and an enhancement in the dimer/monomer ratio, pointing to the presence
      of high amounts of catalytically inactive enzyme. This relative decrease in
      activity could be mainly related to increases in islet asymmetric dimethyl
      arginine content, an endogenous inhibitor of nNOS activity. In addition,
      mitochondrial nNOS level was decreased, which contrasts with a strongly increased
      association with insulin granules. CONCLUSIONS/INTERPRETATION: Increased nNOS
      production and dimerisation, together with a relative decrease in catalytic
      activity and relocalisation, are involved in beta cell hyperactivity in insulin
      resistant rats but also in human islets isolated from obese individuals.

PMID- 21847586
TI  - Laparoscopic lymphadenectomy for gynecologic malignancies: evaluation of the
      surgical approach and outcomes over a seven-year experience.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility and efficacy
      of laparoscopic lymphadenectomy in patients with gynecologic malignancies and
      improve upon the existing published data regarding laparoscopic lymphadenectomy.
      METHODS: We conducted a retrospective chart review of 225 patients with various
      gynecologic malignancies who had undergone laparoscopic pelvic lymphadenectomy
      (LPL) and/or laparoscopic para-aortic lymphadenectomy (LPAL) at Kangbuk Samsung
      Hospital between November 2003 and October 2010. RESULTS: One hundred and seventy
      two patients underwent both LPL and LPAL, 47 patients underwent LPL alone, and
      six patients underwent a repeat laparoscopic lymphadenectomy. The median age and
      body mass index of the patients were 49.4 years (range 23-79 years) and 24.2
      kg/m(2) (range 17.5-37.2 kg/m(2)). The median numbers of harvested pelvic and
      para-aortic lymph nodes were 25.9 (range 3-63) and 10.6 (range 1-34),
      respectively. The median operating times for the LPL and LPAL were 72.3 min
      (range 40-120 min) and 40 min (range 20-70 min), respectively. There were seven
      cases of major vessel injuries, two lymphocytes, two lymphedemas, and two chylous
      ascites. There was no unplanned conversion to laparotomy. CONCLUSIONS:
      Laparoscopic lymphadenectomy can be considered a technically feasible and safe
      procedure and has become the alternative modality in the field of gynecologic
      oncology surgery. And our results could reinforce the existing published data
      regarding laparoscopic lymphadenectomy.

PMID- 21847587
TI  - Cervical sarcoma botryoides and ovarian Sertoli-Leydig cell tumor: a case report
      and review of literature.

PMID- 21847588
TI  - Associations between gene polymorphisms in fatty acid metabolism pathway and
      preterm delivery in a US urban black population.
AB  - There is increasing evidence suggesting that higher intakes of fish or n-3
      polyunsaturated fatty acids supplements may decrease the risk of preterm delivery
      (PTD). We hypothesized that genetic variants of the enzymes critical to fatty
      acids biosynthesis and metabolism may be associated with PTD. We genotyped 231
      potentially functional single nucleotide polymorphisms (SNPs) and tagSNPs in 9
      genes (FADS1, FADS2, PTGS1, PTGS2, ALOX5, ALOX5AP, PTGES, PTGES2, and PTGES3)
      among 1,110 black mothers, including 542 mothers who delivered preterm (<37 weeks
      gestation) and 568 mothers who delivered full-term babies (>=37 weeks gestation)
      at Boston Medical Center. After excluding SNPs that are in complete linkage
      disequilibrium or have lower minor allele frequency (<1%) or call rate (<90%), we
      examined the association of 206 SNPs with PTD using multiple logistic regression
      models. We also imputed 190 HapMap SNPs via program MACH and examined their
      associations with PTD. Finally, we explored gene-level and pathway-level
      associations with PTD using the adaptive rank truncated product (ARTP) methods. A
      total of 21 SNPs were associated with PTD (p value ranging from 0.003 to 0.05),
      including 3 imputed SNPs. Gene-level ARTP statistics indicated that the gene
      PTGES2 was significantly associated with PTD with a gene-based p value equal to
      0.01. No pathway-based association was found. In this large and comprehensive
      candidate gene study, we found a modest association of genes in fatty acid
      metabolism pathway with PTD. Further investigation of these gene polymorphisms
      jointly with fatty acid measures and other genetic factors would help better
      understand the pathogenesis of PTD.

PMID- 21847589
TI  - The insecticide DDT targets the OSCP and subunit D of the Apis mellifera ATP
      synthase.
AB  - 1,1-bis (p-chlorophenyl)-2, 2, 2-trichloroethane (DDT) has been used for control
      of malaria mosquitoes and other insect vectors of human diseases since 1945. Its
      use poses an environmental dilemma and efforts to replace it have been hampered
      by lack of information about its molecular target. This work identifies the 23
      kDa band responsible for the DDT sensitivity in bees, as the OSCP and subunit "d"
      of the ATP synthase. The OSCP of the bee's ATP synthase contained 207 amino acids
      compared to 190 in bovine, which is insensitive to DDT, and the identities were
      only 47%. Subunit "d" of the bees had no counterpart in the bovine. Whether DDT
      is interacting only with OSCP, only with subunit "d", or with both subunits,
      remains to be assessed. Identification of the molecular target of DDT will lead
      the way to new target based insecticides aimed to protect plant, combat malaria
      and other insect transmitted diseases.

PMID- 21847590
TI  - Nanotechnology: emerging tool for diagnostics and therapeutics.
AB  - Nanotechnology is an emerging technology which is an amalgamation of different
      aspects of science and technology that includes disciplines such as electrical
      engineering, mechanical engineering, biology, physics, chemistry, and material
      science. It has potential in the fields of information and communication
      technology, biotechnology, and medicinal technology. It involves manipulating the
      dimensions of nanoparticles at an atomic scale to make use of its physical and
      chemical properties. All these properties are responsible for the wide
      application of nanoparticles in the field of human health care. Promising new
      technologies based on nanotechnology are being utilized to improve diverse
      aspects of medical treatments like diagnostics, imaging, and gene and drug
      delivery. This review summarizes the most promising nanomaterials and their
      application in human health.

PMID- 21847591
TI  - On the dialectics of trauma in Tennessee Williams' A Streetcar Named Desire.
AB  - Blanche DuBois, the tragic heroine of Tennessee Williams' A Streetcar Named
      Desire, has always been read as either "mad" from the start of the play or as a
      character who descends into "madness." We argue that Streetcar adumbrates
      elements of trauma theory, specifically symptoms of post-traumatic stress
      disorder such as involuntary reliving of traumatic events, dissociation, guilt,
      shame, denial, the shattering of the self, the compulsion to repeat the story of
      trauma, as well as the early stages of recovery from trauma. We are the first to
      employ trauma theory as a critical framework through which to view Blanche and
      the dramaturgical devices used to concretize her post-traumatic state of mind.
      Williams' heroine speaks from traumatic experience and not from psychic
      fabrications. Indeed, we contend that the play traces Blanche's deliberate and
      self-conscious working through and mourning of the traumatic losses of the past,
      including her idealized, narcissistic conceptions of herself within a traumatic
      present. Thus she is more attuned to the most disturbing parts of reality and
      exhibits tragic insight born of traumatic experience. Critics who see Blanche as
      "mad" do not fully recognize her struggle to come to terms with trauma and loss
      within a culture of denial. We conclude that Streetcar stages the inextricable
      relation between the individual and social dialectics of trauma.

PMID- 21847592
TI  - From the editors' desk: sticking with the script.

PMID- 21847593
TI  - Predictive value of D-dimer test for recurrent venous thromboembolism at hospital
      discharge in patients with acute pulmonary embolism.
AB  - D-dimer can be used to exclude acute pulmonary embolism (PE) for its high
      negative predictive value (NPV). Also, it is a predictor of recurrent venous
      thromboembolism (VTE) after anticoagulation withdrawal. The aim of the present
      study was to assess the predictive value of D-dimer for recurrent VTE when tested
      at hospital discharge. Plasma D-dimer levels were repeatedly measured at hospital
      discharge in 204 consecutive patients with the first episode of acute pulmonary
      embolism. Patients were categorized to two groups by D-dimer levels at hospital
      discharge and followed up at 3, 6, and 12 months and yearly thereafter. The
      primary end point was symptomatic, recurrent fatal or nonfatal VTE. D-dimer
      levels were persistently abnormal in 66 patients (32%). After 31+/-19 months
      follow-up, patients with persistently abnormal D-dimer level levels showed a
      higher rate of of recurrent VTE (14 patients, 21%) compared to those with D-dimer
      regression (8 patients, 6%) (P = 0.001). At the multivariate analysis, after
      adjustment for other relevant factors, persistently abnormal D-dimer level levels
      were an independent predictor of recurrent VTE in all subjects investigated,
      (hazard ratio, 4.10; 95% CI, 1.61-10.39; P = 0.003), especially in those with
      unprovoked PE (hazard ratio, 4.61; 95% CI, 1.85-11.49; P = 0.001). The negative
      predictive value of D-dimer was 94.2 and 92.9% in all subjects or those with
      unprovoked PE, respectively. Persistently abnormal D-dimer level levels at
      hospital discharge have a high negative predictive value for recurrence in
      patients with acute pulmonary embolism, especially in subjects with an unprovoked
      previous event.

PMID- 21847594
TI  - Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human
      endothelial cells.
AB  - Betel quid (BQ) chewing is a common oral habit in South Asia and Taiwan. BQ
      consumption may increase the risk of oral squamous cell carcinoma (OSCC), oral
      submucous fibrosis (OSF), and periodontitis as well as systemic diseases
      (atherosclerosis, hypertension, etc.). However, little is known about the toxic
      effect of BQ components on endothelial cells that play important roles for
      angiogenesis, carcinogenesis, tissue fibrosis, and cardiovascular diseases. EAhy
      926 (EAHY) endothelial cells were exposed to arecoline, a major BQ alkaloid, for
      various time periods. Cytotoxicity was estimated by 3-(4, 5- dimethylthiazol-2
      yl)-2, 5-diphenyl tetrazolium bromide assay. The cell cycle distribution of EAHY
      cells residing in sub-G0/G1, G0/G1, S-, and G2/M phases was analyzed by propidium
      iodide staining of cellular DNA content and flow cytometry. Some EAHY cells
      retracted, became round-shaped in appearance, and even detached from the culture
      plate after exposure to higher concentrations of arecoline (> 0.4 mM). At
      concentrations of 0.4 and 0.8 mM, arecoline induced significant cytotoxicity to
      EAHY cells. At similar concentrations, arecoline induced G2/M cell cycle arrest
      and increased sub-G0/G1 population, a hallmark of apoptosis. Interestingly,
      prolonged exposure to arecoline (0.1 mM) for 12 and 21 days significantly
      suppressed the proliferation of EAHY cells, whereas EAHY cells showed adaptation
      and survived when exposed to 0.05 mM arecoline. These results suggest that BQ
      components may contribute to the pathogenesis of OSF and BQ chewing-related
      cardiovascular diseases via toxicity to oral or systemic endothelial cells,
      leading to impairment of vascular function. During BQ chewing, endothelial damage
      may be induced by areca nut components and associate with the pathogenesis of
      OSF, periodontitis, and cardiovascular diseases.

PMID- 21847595
TI  - High-resolution spectral domain optical coherence tomography and fundus
      autofluorescence correlation in tubercular serpiginouslike choroiditis.
AB  - OBJECTIVE: This study aims to describe changes in high-resolution spectral domain
      optical coherence tomography (SD-OCT) scans with simultaneous fundus
      autoflorescence (FAF) signals in tubercular serpiginouslike choroiditis (SLC).
      METHODS: Simultaneous SD-OCT and FAF imaging of eyes affected with SLC from acute
      stage until resolution of lesions was obtained using Spectralis HRA+OCT system
      (Heidelberg Engineering, Heidelberg, Germany). PATIENTS: Four eyes (three
      patients) with SLC were prospectively followed. RESULTS: Acute lesions of SLC
      (diffusely hyperautofluorescent) corresponded to hyperreflective areas on SD-OCT
      involving the retinal pigment epithelium (RPE), photoreceptor outer segment tips
      (POST), inner segment-outer segment (IS/OS) junction, external limiting membrane
      (ELM), and outer nuclear layer (ONL) with a minimal distortion of inner retinal
      layers. There was no backscattering from inner choroid. During healing, lesions
      became discrete with a hypoautofluorescent border and predominant
      hyperautofluorescence centrally. The hyperreflective fuzzy areas on SD-OCT scans
      disappeared, and irregular, knobbly elevations of outer retinal layers appeared.
      The RPE, POST, IS/OS junction, and ELM could not be distinguished. The ONL
      appeared normal. The choroid showed an increased reflectance. As the lesions
      healed further over the next 3-6 months, they became predominantly
      hypoautofluorescent with loss of RPE, POST, IS/OS junction, and ELM in SD-OCT
      scan. CONCLUSION: The SD-OCT provided an insight into the ultrastructural changes
      in the outer retina during the course of acute SLC lesions. The changes on OCT
      correlated with abnormal FAF findings.

PMID- 21847597
TI  - Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei
      infected BALB/c mice.
AB  - The present work was undertaken to evaluate the antiplasmodial activity of
      ethanolic leaves extract of traditional medicinal plant Xanthium strumarium in
      Plasmodium berghei-infected BALB/c mice along with phytochemical screening and
      acute toxicity test to support its traditional medicinal use as a malaria remedy.
      The ethanolic leaves extract of X. strumarium (ELEXS) 150, 250, 350 and 500
      mg/kg/day demonstrated dose-dependent chemosuppression during early and
      established infection long with significant (p < 0.001) repository activity. The
      oral administration of 500 mg/kg/day concentration showed a maximum of 88.6%
      chemosuppression during early infection, which was more than that of the standard
      drug chloroquine (5 mg/kg/day) with 88.3% chemosuppression. However, 60%
      mortality has been found in this group. The LD(50) of ELEXS was found to be 1.5
      g/kg/mouse. The administration of 350 mg/kg/day concentration of extract have
      been found to exert 90.40% chemosuppression during repository infection, which
      was well comparable to standard drug pyrimethamine (1.2 mg/kg/day) exerting
      92.91% chemosuppression. The extract has been found to enhance mean survival time
      of mice from 21 to 26 days with 250 and 350 mg/kg/day concentrations, while 150
      mg/kg/day concentration has been found to sustain all the mice up to 29 days
      which was similar to the employed standard drug chloroquine (5 mg/kg/day). All
      these findings support the ethanopharmacological use of X. strumarium as malarial
      remedy and indicate the potential of plant for active antiplasmodial components.

PMID- 21847596
TI  - Neurorobotic and hybrid management of lower limb motor disorders: a review.
AB  - A neurobot (NR) is a mechatronic wearable robot that can be applied to drive a
      paralyzed limb. Through the application of controllable forces, a NR can assist,
      replace, or retrain a certain motor function. Robotic intervention in
      rehabilitation of motor disorders has a potential to improve traditional
      therapeutic interventions. Because of its flexibility, repeatability and
      quantifiability, NRs have been more and more applied in neurorehabilitation.
      Furthermore, combination of NRs with functional electrical stimulation/therapy
      constitutes a trend to overcome a number of practical limitations to widespread
      the application of NRs in clinical settings and motor control studies. In this
      review, we examine the motor learning principles, robotic control approaches and
      novel developments from studies with NRs and hybrid systems, with a focus on
      rehabilitation of the lower limbs.

PMID- 21847598
TI  - The effect of verapamil on in vitro susceptibility of promastigote and amastigote
      stages of Leishmania tropica to meglumine antimoniate.
AB  - Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis
      (CL) with low efficacy and resistance is emerging. CL is increased significantly
      in respect to incidence rate and expanding to new foci. In the present study, the
      effect of verapamil on in vitro susceptibility of promastigote and amastigote
      stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was
      evaluated using colorimetric assay (MTT) and in a macrophage model, respectively.
      Verapamil, as a calcium channel blocker, affects drug uptake by preventing of
      drug efflux from the cells. In promastigote form, several concentrations of MA
      with or without verapamil showed significant decrease (P < 0.05) in optical
      density. The overall mean IC50 value with combination of MA plus verapamil (IC50
      = 116.03 MUg/ml) was significantly less than MA (IC50 = 225.14 MUg/ml) alone (P <
      0.05) for promastigote stage. Similarly, the amastigote stage was more
      susceptible to treatment with MA plus verapamil to that of MA alone (P < 0.05).
      Analysis of overall effect of different concentrations of MA alone, compared with
      combination of MA plus verapamil by mean infection rate of amastigotes in each
      macrophage showed a significant difference (P < 0.05).These findings indicated
      some degree of synergistic effects between MA and verapamil on in vitro
      susceptibility of L. tropica to MA. Further works are required to evaluate this
      synergistic effect on animal model or volunteer human subjects.

PMID- 21847599
TI  - Molecular identification of Mesocestoides spp. from intermediate hosts (rodents)
      in central Europe (Poland).
AB  - Genus Mesocestoides is a representative of the small cyclophyllidean family
      Mesocestoididae that is found parasitizing the small intestine of carnivores. The
      life cycle of cestodes from this genus is complex and requires two intermediate
      hosts. Cysticercoids are produced in the first intermediate host (oribatid
      mites), which when eaten by the second intermediate host (mainly rodents, but
      also other mammalian species, birds, reptiles, or amphibians) form tetrathyridia
      in the body cavity. Because of the rich history of nomenclatural evaluation of
      Mesocestoididae, the taxonomic status within the genus Mesocestoides is still
      unclear. Additional problem constitute the difficulty or even the impossibility
      in the determination of tetrathyridia based on morphological features. Thus, the
      aim of our study was to identify a molecular characteristic of the isolates of
      Mesocestoides from the second intermediate hosts (rodents) based on nuclear and
      mitochondrial ribosomal DNA data. We choose to analyze metacestodes isolated from
      two species of rodents (Apodemus agrarius and Myodes glarolus) from different
      sites. As a result of amplification of 18S rDNA, we obtained partial sequences
      from four isolates ranging from 1,116 to 1,162 bp. In relation to mitochondrial
      sequence, 354 bp product of 12S rDNA was obtained from one isolate. The neighbor
      joining and maximum parsimony trees were constructed in order to examine the
      phylogenetic relationship within Mesocestoides spp. occurring in rodents from
      central Europe. The results of our research on the larval stages from rodents,
      living in a periphery of urban agglomeration as well as in an area of reserve
      protection, confirm the data of more frequently occurring Mesocestoides
      litteratus.

PMID- 21847600
TI  - Enzyme-linked immunosorbent assays for the detection of equine antibodies
      specific to a recombinant Fasciola hepatica surface antigen in an endemic area.
AB  - The utility of an enzyme-linked immunosorbent assay to determine the
      sensitization against the trematode Fasciola hepatica in horses from an endemic
      area (NW Spain) was assessed. Blood samples were collected from 536 horses and
      tested against a 2.9-kDa recombinant surface protein (FhrAPS) to estimate the
      presence of IgG antibodies. Data were analysed regarding several intrinsic (age,
      gender and breed) and extrinsic factors (aptitude and housing). The farm size
      (number of horses/farm) was also considered. Sixty percent (95% CI 56, 64) of the
      horses were positive to the FhrAPS-ELISA, with a significantly higher
      seroprevalence in the mares (67%). Foals reached the lowest percentage of
      sensitization against the trematode (12%), and a significant positive correlation
      between the seroprevalence of fasciolosis and the age of the horses was
      established. When considering all the factors together, the seroprevalence of
      fasciolosis was initially classified into two groups (nodes) regarding the age of
      the horses. The node composed of the horses older than 1 year was then divided
      into two other clusters according to their gender. The mares were finally
      classified and grouped into two nodes regarding their breed. We concluded that
      the FhrAPS-ELISA is very useful for the demonstration of specific equine IgG
      antibodies against F. hepatica. An elevated risk of exposition to this trematode
      in horses maintained in endemic areas was proven. The possible role of horses as
      reservoirs for F. hepatica infections is discussed.

PMID- 21847601
TI  - Science, salmon, and sea lice: constructing practice and place in an
      environmental controversy.
AB  - Over the last three decades salmon aquaculture has become both a significant
      coastal industry and a focus of controversy regarding its environmental impacts.
      Both circumstances have also provoked a great deal of environmental research.
      This article examines one episode in the history of this research. The Broughton
      Archipelago is a region of islands and channels on the Pacific coast of Canada,
      densely populated with salmon farms. Beginning in 2001 this region attracted
      researchers from several institutions, who examined the ecology of the farms, and
      particularly the possibility that they release large numbers of parasites (known
      as sea lice), which then infect wild salmon. This local research community drew
      on aspects of the regional environment, including its ecological conditions, and
      opportunities for surveys, field experiments, and ecological modeling, to
      construct methods that were both situated in this place, yet intended to be
      persuasive to audiences outside the region. Knowledge of this environment was
      also influenced by knowledge from elsewhere, including the results of European
      research on sea lice, and various disciplinary perspectives. Research results
      were invoked to support opposing views of the impacts of salmon farms, as well as
      contrasting perspectives on the region's identity. Sea lice themselves, within
      the context of the ecosystem that gave them meaning, were objectified as the
      ecological link between salmon farms and the environment, and the basis for
      research and debate over these farms. This historical episode therefore
      demonstrates the inseparability of scientific practice, knowledge and place,
      particularly in the context of controversy.

PMID- 21847602
TI  - A Sanctuary for Science: The Hastings Natural History  Reservation and the
      Origins of the University  of California's Natural Reserve System.
AB  - In 1937 Joseph Grinnell founded the University of California's (U.C.) first
      biological field station, the Hastings Natural History Reservation. Hastings
      became a center for field biology on the West Coast, and by 1960 it was serving
      as a model for the creation of additional U.C. reserves. Today, the U.C. Natural
      Reserve System (NRS) is the largest and most diverse network of university-based
      biological field stations in the world, with 36 sites covering more than 135,000
      acres. This essay examines the founding of the Hastings Reservation, and asks how
      it managed to grow and develop, in the 1940s and 1950s, during a time of
      declining support for natural history research. It shows how faculty and staff
      courted the support of key institutional allies, presented themselves as the
      guardians of a venerable tradition in nature study, and emphasized the station's
      capacity to document ecological change and inform environmental policy and
      management. In the years since, Hastings and other U.C. reserves have played
      crucial roles in California environmental politics. Biological field stations in
      the post-war era deserve more attention not only from historians of biology, but
      also from environmental historians and other scholars interested in the role of
      science in society.

PMID- 21847603
TI  - Diagnostic accuracy of endoscopic ultrasonography in patients with inconclusive
      magnetic resonance imaging diagnosis of biliopancreatic abnormalities.
AB  - AIM: To determine the sensitivity and specificity of endoscopic ultrasonography
      (EUS) in patients with inconclusive magnetic resonance imaging/magnetic resonance
      cholangiopancreatography (MRI/MRCP) in pancreatobiliary abnormalities. METHODS:
      During 10 months, patients with pancreatobiliary diseases referred to endoscopic
      retrograde cholangiopancreatography (ERCP) because of inconclusive MRI/MRCP
      diagnosis were scheduled to undergo endoscopic ultrasonography. Patients were
      divided into four major groups: patients with (i) resectable periampullary
      neoplasms who were referred to a surgeon, (ii) unresectable periampullary cancer
      who underwent ERCP for biliary stenting, (iii) bile duct stone who were referred
      to ERCP for stone extraction, and (iv) normal pancreatobiliary tract. Reference
      standards for comparison were ERCP, surgery, a biopsy confirming malignancy, or
      the clinical course during follow up (at least 12 months) in cases without
      evidences of malignancy. RESULTS: One hundred and seven patients (51 men; mean
      [SD] age 60.0 [15.5]) were included in the study. Final diagnoses were common
      bile duct (CBD) stone (n = 24), periampullary neoplasms (n = 46), others (n = 23)
      and no pathologic findings (n = 14). EUS determined the staging for clinical
      decision-making in 47 patients with neoplasms which showed that tumors in 34
      patients (79.1%) were unresectable (advanced stage). After EUS, 47 patients
      (43.9%) did not require ERCP. The accuracy of EUS for the diagnosis of CBD stone
      and periampullary neoplasms were 96.3% and 99.1%, respectively. CONCLUSIONS: EUS
      is a useful modality in cases of inconclusive MRI/MRCP indicating
      pancreatobiliary disorders.

PMID- 21847604
TI  - Obscure pathogenesis of primary iron overload in Indians warrants more focused
      research.

PMID- 21847605
TI  - Esophageal lipoma presenting as a long tongue!!

PMID- 21847606
TI  - Serous microcystic adenoma of pancreas.

PMID- 21847607
TI  - Celiac disease suspected at endoscopy in patients with chronic liver disease.
AB  - Endoscopic findings of celiac disease have high specificity and sensitivity. We
      evaluated records of 137 consecutive patients who had endotherapy for variceal
      hemorrhage, and who had features of celiac disease at endoscopy; patients who had
      such markers at endoscopy had undergone duodenal histology and serology. Thirty
      one patients had changes of portal hypertensive vasculopathy in the duodenum, 8
      had scalloping, and 6 had mosaic pattern; 3 patients also had decreased fold
      height or sparse folds in the descending duodenum. Six of these 8 patients had
      positive serology and histology suggestive of celiac disease. Endoscopic
      evaluation resulted in diagnosis of CD in 4.37% patients of chronic liver disease
      undergoing endotherapy.

PMID- 21847608
TI  - Myosin II activity is required for functional leading-edge cells and closure of
      epidermal sheets in fish skin ex vivo.
AB  - Re-epithelialization in skin wound healing is a process in which epidermal sheets
      grow and close the wound. Although the actin-myosin system is thought to have a
      pivotal role in re-epithelialization, its role is not clear. In fish skin, re
      epithelialization occurs around 500 MUm/h and is 50 times faster than in
      mammalian skin. We had previously reported that leading-edge cells of the
      epidermal outgrowth have both polarized large lamellipodia and "purse string"
      like actin filament cables in the scale-skin culture system of medaka fish,
      Oryzias latipes (Cell Tissue Res, 2007). The actin purse-string (APS) is a
      supracellular contractile machinery in which adherens junctions (AJs) link
      intracellular myosin II-including actin cables between neighboring cells. In this
      study, we developed a modified "face-to-face" scale-skin culture system as an ex
      vivo model to study epidermal wound healing, and examined the role of the actin
      myosin system in the rapid re-epithelialization using a myosin II ATPase
      inhibitor, blebbistatin. A low level of blebbistatin suppressed the formation of
      APS and induced the dissociation of keratocytes from the leading edge without
      attenuating the growth of the epidermal sheet or the migration rate of solitary
      keratocytes. AJs in the superficial layer showed no obvious changes elicited by
      blebbistatin. However, two epidermal sheets without APSs did not make a closure
      with each other, which was confirmed by inhibiting the connecting AJs between the
      superficial layers. These results suggest that myosin II activity is required for
      functional leading-edge cells and for epidermal closure.

PMID- 21847609
TI  - Chemotyping of Fusarium graminearum and F. culmorum isolates from Turkey by PCR
      assay.
AB  - Fusarium graminearum and F. culmorum are the major causal agents of Fusarium head
      blight in Turkey. They produce trichothecenes such as deoxynivalenol (DON),
      nivalenol (NIV) and their several acetylated derivatives, 3-acetyldeoxynivalenol
      (3-ADON) and 15-acetyldeoxynivalenol (15-ADON). In this study, a total of thirty
      three isolates of F. graminearum and F. culmorum were collected from various
      regions and three different hosts. They were identified by amplification of tri5
      gene cluster. Totally 32 isolates, 21 of F. culmorum and 11 of F. graminearum,
      were determined as DON chemotype, while only one F. graminearum isolate (1F) was
      detected as a NIV. A 282 base pair (bp) band for tri13 gene and also ranging from
      458 to 535 bp bands for tri7 gene were amplified in all DON producers' genomes.
      Further analysis of DON chemotype based on tri3 gene amplification showed that
      all isolates of F. graminearum displayed 15-ADON sub-chemotype. They yielded a
      863 bp amplicon. Similarly, 3-ADON sub-chemotype was identified in F. culmorum'
      isolates except F13. As a result of tri3 gene assay, it was produced a 583 bp
      fragment in these twenty isolates. It is the first report that a F. graminearum
      isolate depicts NIV chemotype in agricultural regions of Turkey. According to our
      findings, DON chemotype is predominating in our country. Also, it is presented
      that most of the F. graminearum isolates have 15-ADON sub-chemotype, while all F.
      culmorum's belong to 3-ADON which possess full length amplicon of tri7 gene.

PMID- 21847610
TI  - A convenient route to optically pure alpha-alkyl-beta-(sec-amino)alanines.
AB  - The cyclization of N-Boc-alpha-alkylserines to corresponding beta-lactones under
      Mitsunobu reaction conditions and the ring opening with heterocyclic amines
      (pyrrolidine, piperidine, morpholine and thiomorpholine) produced N-Boc-alpha
      alkyl-beta-(sec-amino)alanines. The removal of the Boc group gives di
      hydrochlorides of non-protein amino acids.

PMID- 21847611
TI  - Effect of two beta-alanine dosing protocols on muscle carnosine synthesis and
      washout.
AB  - Carnosine (beta-alanyl-L-histidine) is found in high concentrations in skeletal
      muscle and chronic beta-alanine (BA) supplementation can increase carnosine
      content. This placebo-controlled, double-blind study compared two different 8
      week BA dosing regimens on the time course of muscle carnosine loading and 8-week
      washout, leading to a BA dose-response study with serial muscle carnosine
      assessments throughout. Thirty-one young males were randomized into three BA
      dosing groups: (1) high-low: 3.2 g BA/day for 4 weeks, followed by 1.6 g BA/day
      for 4 weeks; (2) low-low: 1.6 g BA/day for 8 weeks; and (3) placebo. Muscle
      carnosine in tibialis-anterior (TA) and gastrocnemius (GA) muscles was measured
      by 1H-MRS at weeks 0, 2, 4, 8, 12 and 16. Flushing symptoms and blood clinical
      chemistry were trivial in all three groups and there were no muscle carnosine
      changes in the placebo group. During the first 4 weeks, the increase for high-low
      (TA 2.04 mmol/kgww, GA 1.75 mmol/kgww) was ~twofold greater than low-low (TA 1.12
      mmol/kgww, GA 0.80 mmol/kgww). 1.6 g BA/day significantly increased muscle
      carnosine within 2 weeks and induced continual rises in already augmented muscle
      carnosine stores (week 4-8, high-low regime). The dose-response showed a
      carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA, which was only
      dependent upon the total accumulated BA consumed (within a daily intake range of
      1.6-3.2 g BA/day). Washout rates were gradual (0.18 mmol/kgww and 0.43
      mmol/kgww/week; ~2%/week). In summary, the absolute increase in muscle carnosine
      is only dependent upon the total BA consumed and is not dependent upon baseline
      muscle carnosine, the muscle type, or the daily amount of supplemented BA.

PMID- 21847612
TI  - Simulated environmental criticalities affect transglutaminase of Malus and
      Corylus pollens having different allergenic potential.
AB  - Increases in temperature and air pollution influence pollen allergenicity, which
      is responsible for the dramatic raise in respiratory allergies. To clarify
      possible underlying mechanisms, an anemophilous pollen (hazel, Corylus avellana),
      known to be allergenic, and an entomophilous one (apple, Malus domestica), the
      allergenicity of which was not known, were analysed. The presence also in apple
      pollen of known fruit allergens and their immunorecognition by serum of an
      allergic patient were preliminary ascertained, resulting also apple pollen
      potentially allergenic. Pollens were subjected to simulated stressful conditions,
      provided by changes in temperature, humidity, and copper and acid rain pollution.
      In the two pollens exposed to environmental criticalities, viability and
      germination were negatively affected and different transglutaminase (TGase) gel
      bands were differently immunodetected with the polyclonal antibody AtPng1p. The
      enzyme activity increased under stressful treatments and, along with its
      products, was found to be released outside the pollen with externalisation of
      TGase being predominant in C. avellana, whose grain presents a different cell
      wall composition with respect to that of M. domestica. A recombinant plant TGase
      (AtPng1p) stimulated the secreted phospholipase A(2) (sPLA(2)) activity, that in
      vivo is present in human mucosa and is involved in inflammation. Similarly,
      stressed pollen, hazel pollen being the most efficient, stimulated to very
      different extent sPLA(2) activity and putrescine conjugation to sPLA(2). We
      propose that externalised pollen TGase could be one of the mediators of pollen
      allergenicity, especially under environmental stress induced by climate changes.

PMID- 21847613
TI  - Autoantibodies from patients with celiac disease inhibit transglutaminase 2
      binding to heparin/heparan sulfate and interfere with intestinal epithelial cell
      adhesion.
AB  - Autoantibodies from patients with celiac disease (CD) can influence
      transglutaminase 2 (TG2) activity and its cellular functions, but the exact
      mechanisms have remained unknown. Our objective was to study whether
      autoantibodies could modulate TG2 binding to heparin/heparan sulfate (HS) and
      intestinal epithelial cell attachment to fibronectin-TG2 matrix. Anti-TG2
      antibodies were purified by TG2 affinity chromatography from sera of patients
      with active CD. Serum and antibody effects on TG2 binding to heparin/HS, on
      transamidase activity of TG2, as well as on Caco-2 cell attachment to fibronectin
      TG2 matrix were assessed using microplate assays. Both sera and purified anti-TG2
      antibodies from CD patients with high anti-TG2 IgA levels reduced TG2 binding to
      heparin/HS as compared with those with low anti-TG2 IgA or controls. There was a
      negative correlation between anti-TG2 IgA levels and TG2 binding to heparin/HS.
      Treatment of fibronectin-TG2 coated wells with CD patients' sera or purified anti
      TG2 antibodies reduced attachment of Caco-2 cells onto the plate as compared with
      the control samples. The effect of CD patients' antibodies on Caco-2 cell
      attachment to fibronectin-TG2 matrix occurred independently of the inhibition of
      cell adhesion by Arg-Gly-Asp sequence containing peptides. Anti-TG2
      autoantibodies had no effect on transamidase activity of TG2 in vitro. We suggest
      that modulation of adhesion function of TG2 by autoantibodies from patients with
      CD could be related to the inhibition of TG2 binding to HS residues of cell
      surface proteoglycans and could have possible implications for CD pathogenesis.

PMID- 21847614
TI  - Mechanics of chondrocyte hypertrophy.
AB  - Chondrocyte hypertrophy is a characteristic of osteoarthritis and dominates bone
      growth. Intra- and extracellular changes that are known to be induced by
      metabolically active hypertrophic chondrocytes are known to contribute to
      hypertrophy. However, it is unknown to which extent these mechanical conditions
      together can be held responsible for the total magnitude of hypertrophy. The
      present paper aims to provide a quantitative, mechanically sound answer to that
      question. To address this aim requires a quantitative tool that captures the
      mechanical effects of collagen and proteoglycans, allows temporal changes in
      tissue composition, and can compute cell and tissue deformations. These
      requirements are met in our numerical model that is validated for articular
      cartilage mechanics, which we apply to quantitatively explain a range of
      experimental observations related to hypertrophy. After validating the numerical
      approach for studying hypertrophy, the model is applied to evaluate the direct
      mechanical effects of axial tension and compression on hypertrophy (Hueter
      Volkmann principle) and to explore why hypertrophy is reduced in case of
      partially or fully compromised proteoglycan expression. Finally, a mechanical
      explanation is provided for the observation that chondrocytes do not hypertrophy
      when enzymatical collagen degradation is prohibited (S1Pcko knock-out mouse
      model). This paper shows that matrix turnover by metabolically active
      chondrocytes, together with externally applied mechanical conditions, can explain
      quantitatively the volumetric change of chondrocytes during hypertrophy. It
      provides a mechanistic explanation for the observation that collagen degradation
      results in chondrocyte hypertrophy, both under physiological and pathological
      conditions.

PMID- 21847615
TI  - News on ion channels: erythromelalgia, treatment of episodic ataxia and
      faciobrachial dystonic seizures.

PMID- 21847616
TI  - Letter to the editors: comment on "hereditary sensory and autonomic neuropathy II
      due to novel mutation in the HSN2 gene in Mexican families".

PMID- 21847617
TI  - Intensity contrast as a crucial cue for butterfly landing.
AB  - Papilio butterflies use a tetrachromatic color vision to discriminate a rewarding
      flower, approach, land and take nectar from the flower. In the course of further
      analyzing their foraging behavior in a laboratory condition, we found that some
      butterflies could not land on the target flower even they discriminated and tried
      to land on it, especially when the target was dark. This phenomenon, which we
      call "landing suppression", indicates that the cue for landing differs from the
      cue for visually locating a flower. We hypothesized that a possible cue for
      landing was intensity contrast between the target and background, and have
      initiated to test this hypothesis. We tested the butterflies' landing behavior to
      targets of various colors and intensities presented on background of black or
      various densities of gray. As a result, the landing was most strongly suppressed
      when the intensity contrast was close to zero irrespective of the target colors,
      suggesting that the butterflies used the target-background intensity contrast
      when landing.

PMID- 21847618
TI  - Percent lipid is associated with body size but not task in the bumble bee Bombus
      impatiens.
AB  - In some group-living organisms, labor is divided among individuals. This
      allocation to particular tasks is frequently stable and predicted by individual
      physiology. Social insects are excellent model organisms in which to investigate
      the interplay between physiology and individual behavior, as division of labor is
      an important feature within colonies, and individual physiology varies among the
      highly related individuals of the colony. Previous studies have investigated what
      factors are important in determining how likely an individual is, compared to
      nestmates, to perform certain tasks. One such task is foraging. Corpulence (i.e.,
      percent lipid) has been shown to determine foraging propensity in honey bees and
      ants, with leaner individuals being more likely to be foragers. Is this a general
      trend across all social insects? Here we report data analyzing the individual
      physiology, specifically the percent lipid, of worker bumble bees (Bombus
      impatiens) from whom we also analyze behavioral task data. Bumble bees are also
      unusual among the social bees in that workers may vary widely in size.
      Surprisingly we find that, unlike other social insects, percent lipid is not
      associated with task propensity. Rather, body size closely predicts individual
      relative lipid stores, with smaller worker bees being allometrically fatter than
      larger worker bees.

PMID- 21847619
TI  - Pain complaints as risk factor for mental distress: a three-year follow-up study.
AB  - The main aim of this study was to investigate the effect of pain complaints at
      baseline and mental distress at follow-up. We included adolescents from two
      longitudinal studies of 18/19 years of age with two corresponding cross-sectional
      baseline studies at age 15/16. A total of 5750 were invited for the baseline
      study, and we have 3-year follow-up data for 3316 (57.8% follow-up rate). All
      information is based on self-report. The questions of pain are asking for severe
      pain the past year. Mental distress is measured by Hopkins Symptoms Check List
      (HSCL-10). Number of pain sites increased among girls and decreased among boys
      from baseline to follow-up. There was a cross-sectional dose-response association
      between number of pain sites and mental distress at both time points. Also, in
      the follow-up study, there was dose-response relationship between numbers of pain
      sites at baseline and mental distress at follow-up even after controlling for
      possible confounding factors. We found no effect of mental distress at baseline
      on pain reports at follow-up. There is a strong association between pain at 15/16
      years and mental distress at 18/19 years of age. Clinicians should therefore take
      pain complaints among adolescents seriously and be aware of comorbid and later
      development of mental health problems.

PMID- 21847620
TI  - Psychological characteristics, stressful life events and deliberate self-harm:
      findings from the Child & Adolescent Self-harm in Europe (CASE) Study.
AB  - There is evidence to suggest that both psychological characteristics and
      stressful life events are contributory factors in deliberate self-harm among
      young people. These links, and the possibility of a dose-response relationship
      between self-harm and both psychological health and life events, were
      investigated in the context of a seven-country school-based study. Over 30,000,
      mainly 15 and 16 year olds, completed anonymous questionnaires at secondary
      schools in Belgium, England, Hungary, Ireland, the Netherlands, Norway and
      Australia. Pupils were asked to report on thoughts and episodes of self-harm,
      complete scales on depression and anxiety symptoms, impulsivity and self-esteem
      and indicate stressful events in their lives. Level and frequency of self-harm
      was judged according to whether they had thought about harming themselves or
      reported single or multiple self-harm episodes. Multinomial logistic regression
      assessed the extent to which psychological characteristics and stressful life
      events distinguished between adolescents with different self-harm histories.
      Increased severity of self-harm history was associated with greater depression,
      anxiety and impulsivity and lower self-esteem and an increased prevalence of all
      ten life event categories. Female gender, higher impulsivity and experiencing the
      suicide or self-harm of others, physical or sexual abuse and worries about sexual
      orientation independently differentiated single-episode self-harmers from
      adolescents with self-harm thoughts only. Female gender, higher depression, lower
      self-esteem, experiencing the suicide or self-harm of others, and trouble with
      the police independently distinguished multiple- from single-episode self
      harmers. The findings reinforce the importance of psychological characteristics
      and stressful life events in adolescent self-harm but nonetheless suggest that
      some factors are more likely than others to be implicated.

PMID- 21847621
TI  - Down-regulation of Leucaena leucocephala cinnamoyl CoA reductase (LlCCR) gene
      induces significant changes in phenotype, soluble phenolic pools and lignin in
      transgenic tobacco.
AB  - cDNA and genomic clones of cinnamoyl CoA reductase measuring 1011 and 2992 bp
      were isolated from a leguminous pulpwood tree Leucaena leucocephala, named as
      LlCCR. The cDNA exhibited 80-85% homology both at the nucleotide and amino acid
      levels with other known sequences. The genomic sequence contained five exons and
      four introns. Sense and antisense constructs of LlCCR were introduced in tobacco
      plants to up and down-regulate this key enzyme of lignification. The primary
      transformants showed a good correlation between CCR transcript levels and its
      activity. Most of the CCR down-regulated lines displayed stunted growth and
      development, wrinkled leaves and delayed senescence. These lines accumulated
      unusual phenolics like ferulic and sinapic acids in cell wall. Histochemical
      staining suggested reduction in aldehyde units and increased syringyl over
      guaiacyl (S/G) ratio of lignin. Anatomical studies showed thin walled, elongated
      xylem fibres, collapsed vessels with drastic reduction of secondary xylem. The
      transmission electron microscopic studies revealed modification of ultrastructure
      and topochemical distribution of wall polysaccharides and lignin in the xylem
      fibres. CCR down-regulated lines showed increased thickness of secondary wall
      layers and poor lignification of S2 and S3 wall layers. The severely down
      regulated line AS17 exhibited 24.7% reduction of Klason lignin with an increase
      of 15% holocellulose content. Contrarily, the CCR up-regulated lines exhibited
      robust growth, development and significant increase in lignin content. The
      altered lignin profiles observed in transgenic tobacco lines support a role for
      CCR down-regulation in improving wood properties of L. leucocephala exclusively
      used in the pulp and paper industry of India.

PMID- 21847622
TI  - Repeat treatment for recurrent hepatocellular carcinoma: is it validated?
AB  - PURPOSE: Hepatocellular carcinoma (HCC) usually recurs repeatedly and
      locoregional treatment is attempted unless liver function has deteriorated. This
      study was aimed to evaluate the effect of repeated treatment on patient
      prognosis. METHODS: The HCC recurrence pattern and types of treatment for
      recurrence after hepatic resection were reviewed in 134 patients. The effects of
      repeated treatment on prognosis were evaluated. Univariate and multivariate
      analyses were performed to determine the prognostic predictors after initial
      recurrence. RESULTS: Median number of treatments after recurrence was 3 (range, 0
      12). Transarterial chemoembolization was the most common treatment. The number of
      treatments, but not the type of treatment, was associated with the prognosis.
      Multivariate analysis showed that a >20% indocyanine green retention rate at 15
      min (hazard ratio [HR] = 2.65; 95% confidential interval [CI], 1.53-5.62), size
      of primary tumor >5 cm (HR = 1.81; 95% CI, 1.05-3.08), recurrence-free interval
      <1 year (HR = 2.17; 95% CI, 1.28-3.81), size of recurrent tumor >3 cm (HR = 2.61;
      95% CI, 1.03-5.77-0.95), and extrahepatic recurrence (HR = 6.35; 95% CI, 3.49
      11.39) were independent predictors of poor survival. CONCLUSION: The prognosis
      after recurrence is poor in cases with large tumors or poor liver function.
      Repeated locoregional treatment contributes to prolong patient prognosis,
      especially in cases with a small tumor size, long recurrence-free interval, and
      no extrahepatic metastases.

PMID- 21847624
TI  - Patterns of molecular variation in a species-wide germplasm set of Brassica
      napus.
AB  - Rapeseed (Brassica napus L.) is the leading European oilseed crop serving as
      source for edible oil and renewable energy. The objectives of our study were to
      (i) examine the population structure of a large and diverse set of B. napus
      inbred lines, (ii) investigate patterns of genetic diversity within and among
      different germplasm types, (iii) compare the two genomes of B. napus with regard
      to genetic diversity, and (iv) assess the extent of linkage disequilibrium (LD)
      between simple sequence repeat (SSR) markers. Our study was based on 509 B. napus
      inbred lines genotyped with 89 genome-specific SSR primer combinations. Both a
      principal coordinate analysis and software STRUCTURE revealed that winter types,
      spring types, and swedes were assigned to three major clusters. The genetic
      diversity of winter oilseed rape was lower than the diversity found in other
      germplasm types. Within winter oilseed rape types, a decay of genetic diversity
      with more recent release dates and reduced levels of erucic acid and
      glucosinolates was observed. The percentage of linked SSR loci pairs in
      significant (r (2) > Q (95 unlinked loci pairs)) LD was 6.29% for the entire
      germplasm set. Furthermore, LD decayed rapidly with distance, which will allow a
      relatively high mapping resolution in genome-wide association studies using our
      germplasm set, but, on the other hand, will require a high number of markers.

PMID- 21847623
TI  - Pancreatic injury in 284 patients with severe abdominal trauma: outcome, course,
      and treatment algorithm.
AB  - PURPOSE: The relevance of pancreatic trauma in severely injured patients within a
      large collective has not been thoroughly analyzed yet. This study aimed at
      assessing the prevalence of pancreatic trauma in relation to the outcome and the
      currently established algorithm of treatment. METHODS: Some 51,425 patients from
      the Trauma Register of the German Society of Trauma Surgery (TR DGU) (1993-2009)
      were retrospectively analyzed. All patients with an "injury severity score" >=16,
      direct admission to a trauma center and subsequent treatment for at least 3 days,
      age >=16, and an abdominal injury [abbreviated injury scale (AIS)(abdomen) >=2]
      were included. Patients with abdominal trauma (AIS(abdomen) >=2) were compared
      with patients with an additional pancreatic trauma (AIS(pancreas) 2-5). RESULTS:
      Of 51,425 patients, 9,268 (18%) had documented abdominal injuries. Two hundred
      eighty-four (3.1%) patients with abdominal injury additionally showed a
      pancreatic injury (AIS(abdomen) >=2, AIS(pancreas) 2-5) and were analyzed in
      dependency of the classification of the American Association for the Surgery of
      Trauma (AAST) organ severity score. AAST-pancreas: II degrees , 1.9%; III degrees
      , 0.6%; IV degrees , 0.3%; and V degrees , 0.2%. Patients with leading pancreatic
      injury (grades IV and V) thereby showed a significant increase of mortality (IV
      degrees , 30.0% and V degrees , 33.3%) and an increase of the need for surgical
      intervention (IV degrees , 80.6% and V degrees : 81.8%). CONCLUSIONS: The results
      presented here show the prevalence and the outcome of pancreas injury in a large
      collective within the TR DGU for the first time. Based on the current literature
      and the findings, a treatment algorithm has been developed.

PMID- 21847625
TI  - Microglial pathology in Down syndrome.
AB  - Subjects with Down syndrome (DS) inevitably develop histopathological features
      pathognomonic of Alzheimer's disease (AD), and DS can therefore be considered a
      human model of AD. Similar to AD, microglial activation has been reported in DS
      and the idea that detrimental neuroinflammation plays a key role in the
      pathogenesis of neurodegeneration is firmly embedded. However, recent work from
      this laboratory has offered evidence for an alternative view regarding the role
      of microglial cells in AD pathogenesis by showing presence of dystrophic
      (senescent) rather than activated microglia in both the AD and DS brain. In this
      report, we build on previously published observations in human brain and offer a
      detailed analysis of microglial senescent pathology in the temporal cortices of 6
      DS cases in their 40s, a critical age bracket where virtually all DS subjects
      acquire neurofibrillary degeneration characteristic of AD. Our findings using
      both Iba1 and anti-ferritin immunostaining of microglial cells show that
      coincident with the appearance of tau pathology in DS subjects there is
      consistent presence of dystrophic microglial cells and conspicuous absence of
      activated microglia using both markers. The extent of microglial pathology varied
      among the individual DS cases, but they all revealed decreased numbers of normal
      microglia ranging from 19 to 85% of the controls. Nearly all of the ferritin
      positive microglia, which constitute a subset of the total Iba1-reactive
      microglial population, exhibited dystrophic morphology. In its most severe form
      dystrophy was evident as total fragmentation of the cells' cytoplasm
      (cytorrhexis), which likely reflects terminal degeneration of microglia. Severely
      dystrophic, ferritin-positive cells were often found to be colocalized with tau
      positive senile plaques. Our findings help to consolidate the idea that
      microglial degeneration and neurofibrillary degeneration are closely linked
      events in a human model of AD. They suggest that microglial degeneration follows
      a gradually progressive course that increases in its severity in parallel with
      the progression of AD neurodegenerative changes.

PMID- 21847626
TI  - Transportin1: a marker of FTLD-FUS.
AB  - The term frontotemporal lobar degeneration (FTLD) describes a group of disorders
      that are subdivided by the presence of one of a number of pathological proteins
      identified in the inclusion bodies observed post-mortem. The FUS variant is
      defined by the presence of the fused in sarcoma protein (FUS) in the pathological
      inclusions. However, similar to other FTLDs, the disease pathogenesis of FTLD-FUS
      remains largely poorly understood. Here we present data that the protein
      transportin1 (TRN1) is abundant in the FUS-positive inclusions. TRN1, the protein
      product of the TNP01 gene, is responsible for shuttling proteins containing an M9
      nuclear localisation signal between the nuclear and cytoplasmic compartments. RNA
      interacting proteins, including FUS, have been implicated as targets of TRN1.
      Using TRN1 immunohistochemistry and Western blotting in this study, we
      investigated 13 cases of FTLD-FUS including 6 cases with neuronal intermediate
      filament inclusion disease (NIFID) and 7 atypical frontotemporal lobar
      degeneration with ubiquitinated inclusion (aFTLD-U) cases. The data from our
      immunohistochemical studies show that FUS-immunoreactive inclusions are also
      strongly labelled with the anti-TRN1 antibody and double-label immunofluorescence
      studies indicate good co-localisation between the FUS and TRN1 pathologies. Our
      biochemical investigations demonstrate that urea-soluble TRN1 is present in aFTLD
      U and NIFID, but not in normal control brains. These findings implicate
      abnormalities of FUS transport in the pathogenesis of FTLD-FUS.

PMID- 21847627
TI  - Associations between cytotoxic T lymphocyte-associated antigen-4 polymorphisms
      and serum tumor necrosis factor-alpha and interferon-gamma levels in patients
      with chronic hepatitis B virus infection.
AB  - BACKGROUND: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphism,
      which may affect host immune response including cytokines production, is thought
      to be associated with hepatitis B virus (HBV) infection. This study investigated
      the associations between CTLA4 polymorphism and serum tumor necrosis factor (TNF)
      alpha and interferon (IFN)-gamma levels in patients with chronic HBV infection.
      METHODS: CTLA4 promoter -318C/T and exon 1 +49A/G polymorphisms and serum TNF
      alpha and IFN-gamma levels were determined in 172 patients with chronic HBV
      infection and 145 healthy controls. RESULTS: The genotype of CTLA4 -318C/T
      polymorphism had no association to TNF-alpha and IFN-gamma levels. Serum levels
      of TNF-alpha and IFN-gamma in chronic HBV patients with +49GG genotype were lower
      than those with +49AG genotype (p = 0.030 and p = 0.042, respectively), and
      haplotypes -318C + 49A and -318C + 49G seemed to have no significant effects on
      TNF-alpha and IFN-gamma levels. CONCLUSIONS: CTLA4 +49GG genotype was associated
      to lower TNF-alpha and IFN-gamma levels in patients with chronic HBV infection
      but this association was diminished by haplotype formation with -318C/T alleles,
      indicating that the influence of CTLA4 -318C/T and +49A/G polymorphisms on the
      susceptibility and disease progress of chronic HBV infection may not be
      effectuated by affecting TNF-alpha and IFN-gamma secretion.

PMID- 21847628
TI  - Interleukin 29 enhances expression of Toll receptor 3 and mediates antiviral
      signals in human keratinocytes.
AB  - OBJECTIVE: Interleukin 29 (IL-29) is a class II cytokine and displays numerous
      immune functions other than its anti-viral and antiproliferation activities. This
      study is focused on the effect of IL-29 on human keratinocytes (KCs). METHODS:
      Primary KCs were stimulated by various concentrations of IL-29 for different time
      periods, and antiviral proteins and TLR3 gene expression were then analyzed by
      real-time PCR. The signal pathways activated by IL-29 in KCs were detected by
      western blot. The antiviral activity of IL-29 was determined by
      methylthiazolyldiphenyl-tetrazolium bromide, and small interfering RNA knockdown
      was used to analyze the role of toll receptor 3 (TLR3) in the antiviral activity
      of IL-29. RESULTS: IL-29 was able to induce expression of antiviral proteins and
      TLR3 gene expression in KCs. IL-29 pretreatment strongly enhanced herpes simplex
      virus type 1 (HSV-1)-induced expression of the interferon beta (IFN-beta) gene
      and protected the KCs from HSV-1 challenge. The IL-29 antiviral activity was
      partially dependent on TLR3 expression induced by this cytokine, and mechanistic
      studies demonstrated that the regulation of TLR3 expression by IL-29 might be
      partially dependent on Janus kinase /signal transducer and activator of
      transcription (JAK-STATs) activation. CONCLUSION: IL-29-induced TLR3 expression
      is involved in antiviral activity of IL-29 in KCs, which suggests a feasible
      method to cure certain viral infections of the skin.

PMID- 21847631
TI  - Combination of targeted therapy and immunotherapy in melanoma.
AB  - The treatment of human melanoma has progressed markedly in recent years. Building
      on the observation that immune recognition is a frequent event in melanoma, a
      series of immunotherapeutic approaches have been evaluated in clinical trials,
      culminating in the first phase III study improving overall survival of melanoma
      patients since 20 years. However, the response rates seen upon immunotherapeutic
      interventions such as anti-CTLA4 treatment are often low. Furthermore, clinical
      responses can take several weeks to develop, during which time stage IV melanoma
      patients often deteriorate. Recent advances in our understanding of the genetic
      lesions in human melanoma now also allow the specific targeting of the signaling
      pathway alterations in this disease. Such targeted therapies can lead to high
      response rates, although the duration of these responses is thus far relatively
      short. We suggest that the combination of immuno and targeted therapy offers
      potential for synergy for both conceptual and practical reasons. In this review,
      we will discuss the potential and possible limitations for such combination
      therapy, and we describe the most promising combinations of targeted therapy and
      immunotherapy that can be tested in the clinic in the coming years. The concept
      of induction therapy by small molecule administration and consolidation by
      immunotherapeutics also has potential for the treatment of other human cancers.

PMID- 21847629
TI  - Exploring translocation of proteins on DNA by NMR.
AB  - While an extensive body of knowledge has accumulated on the structures of
      transcription factors, DNA and their complexes from both NMR and crystallography,
      much less is known at a molecular level regarding the mechanisms whereby
      transcription factors locate their specific DNA target site within an
      overwhelming sea of non-specific DNA sites. Indirect kinetic data suggested that
      three processes are involved in the search procedure: jumping by dissociation of
      the protein from the DNA followed by re-association at another site, direct
      transfer from one DNA molecule or segment to another, and one-dimensional
      sliding. In this brief perspective I summarize recent NMR developments from our
      laboratory that have permitted direct characterization of the species and
      molecular mechanisms involved in the target search process, including the
      detection of highly transient sparsely-populated states. The main tool in these
      studies involves the application of paramagnetic relaxation enhancement,
      supplemented by z-exchange spectroscopy, lineshape analysis and residual dipolar
      couplings. These studies led to the first direct demonstration of rotation
      coupled sliding of a protein along the DNA and the direct transfer of a protein
      from one DNA molecule to another without dissociating into free solution.

PMID- 21847632
TI  - Interleukin-7 up-regulates cyclin D1 via activator protein-1 to promote
      proliferation of cell in lung cancer.
AB  - Interleukin-7 is a potent regulator of lymphocyte proliferation, but it inducing
      growth of solid tumors is few known. We study the relationship between
      Interleukin-7 and the regulator of the cell cycle, cyclin D1 and the mechanism of
      Interleukin-7 regulating cell growth in human lung cancer. We detected expression
      of cyclin D1 and its impact on the prognosis of lung cancer patients. Using
      Western blot, reverse transcriptase-PCR, Co-Immunoprecipitation, and Chromatin
      Immunoprecipitation, we investigated how Interleukin-7 regulated cyclin D1 in
      vitro and in nude mice. We found that, in lung cancer cell lines and in nude
      mice, Interleukin-7/Interleukin-7 receptor increased the expression of cyclin D1
      and phosphorylation of c-Fos/c-Jun, induce c-Fos and c-Jun heterodimer formation,
      and enhanced c-Fos/c-Jun DNA-binding activity to regulate cyclin D1. In addition,
      lymph node metastasis, tumor stage, and cyclin D1 were the strongest predictors
      of survival in 100 human non-small cell lung cancer specimens analyzed. Taken
      together, our results provided evidence that Interleukin-7/Interleukin-7 receptor
      induced cyclin D1 up-regulation via c-Fos/c-Jun pathway to promote proliferation
      of cells in lung cancer.

PMID- 21847633
TI  - Lentivirus-mediated overexpression of microRNA-199a inhibits cell proliferation
      of human hepatocellular carcinoma.
AB  - microRNA-199a (miR-199a) is a highly conserved miRNA, always deregulated in
      numerous human tumors. The results of microarray analysis indicated that miR-199a
      was frequently downregulated in hepatocellular carcinoma (HCC). The expression
      levels of miR-199a in 11 pairs of matched HCC neoplastic and adjacent non
      neoplastic tissues, 5 HCC cell lines and liver cell line L02 were examined by
      quantitative real-time PCR analysis. We found miR-199a was significantly down
      regulated in HCC tissues when compared with pair-matched adjacent non-tumor
      tissues. We also found the expression level of miR-199a was also substantially
      decreased in several human HCC cell lines including SMMC-7721, BEL-7402, BEL
      7701, MHCC97H, and HepG2. To investigate the role of miR-199a in tumorigenesis,
      we developed a lentiviral vector for the expression of pre-miR-199a (Lenti-miR
      199a). Lenti-miR-199a inhibited HCC cell proliferation in vitro and in vivo.
      Compared to parental cells or cells transfected with a control vector, the
      overexpression of microRNA-199a in the HCC cell lines HepG2 stably was showed to
      reduce cell proliferation in vitro and in vivo. Luciferase reporter assay
      revealed the regulation of miR-199a on 3'-UTR of HIF-1alpha. Further
      investigation confirmed that miR-199a significantly reduced the endogenous
      protein level of HIF-1alpha in hypoxia. MiR-199a inhibits cell proliferation in
      vitro and in vivo partly through down-regulation of HIF-1alpha in human HCC.
      Thus, these studies provide an important new insight into the pathogenesis of
      human HCC and it may open a new perspective for the development of effective gene
      therapy for human HCC.

PMID- 21847634
TI  - Development of a PCR/ligase detection reaction/nanogold-based universal array
      approach for the detection of low-abundant DNA point mutations.
AB  - The aim of this study was to investigate the feasibility of combining PCR and
      ligase detection reaction (LDR) with a novel nano-gold-based universal array for
      the detection of low abundance point mutations from fetal DNA in maternal plasma
      samples. The sequence with the target point mutation was first amplified by PCR
      and then used as a template for LDR in which the upstream specific primer
      contains a tag sequence at the 5'-end. After hybridization to the probes of a
      universal array containing anti-tag sequences, the ligated products were bound to
      streptavidin-labeled nano-gold particles and the hybridization signals were
      amplified by silver staining. The PCR/LDR/universal array was first tested for
      sensitivity with nano-gold-based detection, and then this system was applied to
      detect the low abundance specific mutation IVS2 654(C->T) of the beta-globin gene
      in a model using maternal plasma samples. The nano-gold-based method
      unambiguously identified a single mutation at a sensitivity of 1:1000. This
      approach was applied to detect the paternally inherited IVS2 654(C->T) mutation
      from thirty maternal plasma samples. The results were consistent with those
      obtained by PCR/reverse dot blot of amniotic fluid cell DNA. The PCR/LDR/nano
      gold-based universal array is able to detect low-abundance point mutations with
      high sensitivity.

PMID- 21847635
TI  - A Bayesian hierarchical nonlinear mixture model in the presence of artifactual
      outliers in a population pharmacokinetic study.
AB  - The purpose of this study is to develop a statistical methodology to handle a
      large proportion of artifactual outliers in a population pharmacokinetic (PK)
      modeling. The motivating PK data were obtained from a population PK study to
      examine associations between PK parameters such as clearance of dexmedetomidine
      (DEX) and cytochrome P450 2A6 phenotypes. The blood samples were sparsely sampled
      from patients in intensive care units (ICUs) while different doses of DEX were
      continuously infused. Conventional population PK analysis of these data revealed
      several challenges and intricacies. Especially, there was strong evidence that
      some plasma drug concentrations were artifactually high and likely contaminated
      with the infused drug due to blood sampling processes that are sometimes
      unavoidable in an ICU setting. If not addressed, or if arbitrarily excluded,
      these outlying values could lead to biased estimates of PK parameters and miss
      important relationships between PK parameters and covariates due to increased
      variability. We propose a novel population PK model, a Bayesian hierarchical
      nonlinear mixture model, to accommodate the artifactual outliers using a finite
      mixture as the residual error model. Our results showed that the proposed model
      handles the outliers well. We also conducted simulation studies with a varying
      proportion of the outliers. These simulation results showed that the proposed
      model can accommodate the outliers well so that the estimated PK parameters are
      less biased.

PMID- 21847636
TI  - Exhalation of 131I after radioiodine therapy: measurements in exhaled air.
AB  - PURPOSE: A considerable amount of radioiodine is exhaled after radioiodine
      therapy leading to unwanted radiation exposure through inhalation. This study
      focused on the concentration of radioactivity exhaled and its chemical nature.
      METHODS: Air exhaled by 47 patients receiving (131)I-iodine for different thyroid
      diseases (toxic goitre n = 26, Graves' disease n = 13, thyroid cancer n = 8) was
      investigated with a portable constant air-flow sampler. Different chemical iodine
      species were collected separately (organic, elemental and aerosolic) up to 26 h
      after administration of the radioiodine capsule. The data approximated to a
      monoexponential time-activity curve when integrated over 100 h. The radioactivity
      in the filters was measured with a well counter at defined time points after
      administration. RESULTS: The radioactivity of (131)I in the exhaled air 1 h after
      administration ranged from 1 to 100 kBq/m(3). Two parameters (half-life of
      radioiodine exhalation and time-integrated activity over 100 h) were
      substantially higher in patients with cancer after near-total thyroidectomy (11.8
      +/- 2.1 h and 535 +/- 140 kBq / m(3), respectively) than in patients with
      hyperfunctioning thyroid tissue due to toxic adenoma (7.6 +/- 2.5 h and 115 +/-
      27 kBq / m(3), respectively) or Graves' disease (6.4 +/- 3.6 h and 113 +/- 38 kBq
      / m(3), respectively). The percentage of radioiodine in the exhaled air in
      relation to radioiodine administered to the patient was between 80 ppm and 150
      ppm. The fraction of organically bound radioiodine (mean value) for all time
      points after administration was 94-99.9%. This percentage did not depend on the
      type of thyroid disease. CONCLUSION: The amount of exhaled radioiodine is small
      but by no means negligible on the first day after administration. This is the
      first study to provide experimental evidence on a systematic basis that
      radioiodine becomes exhalable in vivo, i.e. in the patient. The mechanism of
      organification of orally administered radioiodine remains to be investigated.

PMID- 21847637
TI  - The diagnostic value of adding dynamic scintigraphy to standard delayed planar
      imaging for sentinel node identification in melanoma patients.
AB  - PURPOSE: The aim of this study was to compare early dynamic imaging combined with
      delayed static imaging and single photon emission computed tomography (SPECT)/CT
      with delayed, planar, static imaging alone for sentinel node (SN) identification
      in melanoma patients. METHODS: Three hundred and seven consecutive melanoma
      patients referred for SN biopsy (SNB) were examined using combined imaging.
      Secondary interpretation of only the delayed static images was subsequently
      performed. In 220 patients (72%), complete surgical and pathological information
      relating to the SNB was available. The number of SNs identified and number of
      patients with positive SNs were compared between the two interpretations of the
      imaging studies and, when available, related to pathology data. RESULTS: A
      slightly higher number of SNs (mean 0.12/patient) was identified when
      interpreting only delayed static images compared to combined imaging. In a direct
      patient-to-patient comparison, the number of SN(s) identified on the combined vs
      static images only showed moderate agreement (kappa value 0.56). In 38 patients
      (17%), positive SNs were identified by the combined procedure compared to 35
      (16%) by static imaging only. Thus by static imaging only, tumour-positive SNs
      were not identified in 3 of 38 patients (8%). CONCLUSION: For SN identification
      in melanoma patients, dynamic imaging combined with delayed static imaging and
      SPECT/CT is superior to delayed static imaging only because the latter is more
      likely to fail to identify SNs containing metastases.

PMID- 21847638
TI  - Colorectal cancer: prognostic role of 18F-FDG-PET/CT.

PMID- 21847639
TI  - [Translational approaches in cancer stem cell research].
AB  - There has been a growing body of evidence in recent years to indicate that the
      presence of cancer stem cells may be responsible for tumour development and early
      recurrence after conventional therapy strategies such as surgery, radiation, or
      chemotherapy. Although this concept of a small subpopulation of cancer cells with
      stem cell properties is not new as such and was already discussed by Virchow
      decades ago, the identification of cells of this kind in human malignancies was
      first successful in 1997 in acute myeloid leukemia. The recent identification of
      cancer stem cells and the detection of their fundamental signalling pathways
      (e.g. Hedgehog, Notch) may offer new therapeutic options in the future and become
      part of a therapeutic concept. In this article, we introduce the cancer stem cell
      model, provide an overview of current cancer stem cell markers in different human
      malignancies as well as head and neck squamous cell carcinoma, and discuss
      studies on the first targeted therapies against cancer stem cells and their
      signalling pathways.

PMID- 21847640
TI  - [Pharmacological characterization of head and neck cancer in ex-vivo tests].
AB  - Precise knowledge about the chance of success of a given pharmacologic therapy of
      head and neck squamous cell carcinoma (HNSCC) before starting therapy would be
      very desirable to guide the selection of the most suitable or the most efficient
      combination out of the ever-growing spectrum of available pharmaceuticals. This
      selection has hitherto been made at best on the basis of the availability of
      guideline-conformant and approved combinations according to results of published
      clinical studies and approved general effectiveness in HNSCC. However, the
      inhomogeneous biology of HNSCC depending on localization, varying metastatic
      behavior, TNM and UICC stage in the context of the patient's general condition
      and risk status according to lifestyle and occupational exposure make it
      impossible to accurately predict the success of pharmacological therapy regimens
      for the individual HNSCC based on today's clinical and pathohistological
      diagnostics. A solution may lie in the testing of biopsy specimens ex vivo before
      starting therapy. The present review describes recent advances in ex-vivo tests
      and discusses the requirements for their inclusion in the decision-making
      process.

PMID- 21847641
TI  - [Esophageal dysmotility defined with manometry: what does it mean for antireflux
      surgery?].

PMID- 21847642
TI  - The vitamin D pathway and mammographic breast density among postmenopausal women.
AB  - Laboratory studies have demonstrated that vitamin D has a number of
      chemopreventive properties, and that these properties may be mediated or modified
      by other molecules in the vitamin D pathway, such as parathyroid hormone (PTH) or
      calcium. However, there is little epidemiologic data exploring the effects of
      vitamin D on breast cancer risk in the context of these other molecules. We
      examined a panel of molecules in the vitamin D pathway in relation to
      mammographic breast density, a marker of breast cancer risk, in the Wisconsin
      Breast Density Study. A total of 238 postmenopausal women (ages 55-70, with no
      history of postmenopausal hormone use) were enrolled from mammography clinics in
      Madison, Wisconsin. Subjects provided blood samples that were analyzed for levels
      of 25-hydroxy vitamin D [25(OH)D], PTH, insulin-like growth factor-1 (IGF-1), IGF
      binding protein 3 (IGFBP-3), retinol, and calcium. Percent breast density was
      measured using Cumulus software. In age-adjusted analyses there was a positive
      association between 25(OH)D and percent breast density (P = 0.05; mean percent
      density = 11.3% vs. 15.6% for 1st vs. 4th quartile of 25(OH)D). Breast density
      was inversely associated with PTH (P = 0.05; 16.0% vs. 11.4% for Q1 vs. Q4) and
      positively associated with the IGF-1:IGFBP-3 molar ratio (P = 0.02; 11.9% vs.
      15.6% for Q1 vs. Q4). However, these associations were all null after further
      adjustment for body mass index (BMI; P > 0.25). The independent relation between
      25(OH)D and breast density remained null among subgroups defined by BMI and serum
      levels of retinol, calcium, and estradiol. These results suggest no strong
      independent associations between the circulating molecules of the vitamin D
      pathway and mammographic breast density in postmenopausal women. While it remains
      possible that vitamin D could influence breast cancer risk, our results suggest
      that such an effect would be mediated through pathways other than breast density.

PMID- 21847643
TI  - Characteristics of double heterozygosity for BRCA1 and BRCA2 germline mutations
      in Korean breast cancer patients.
AB  - To investigate clinical, pathological, and familial characteristics of Korean
      patients with double heterozygosity for BRCA1 and BRCA2 mutations, six breast
      tumors of five patients who carried deleterious mutations in both of the genes
      were included. Medical records of the patients were reviewed and genetic testing
      by direct sequencing was undertaken to detect mutations in BRCA1 and BRCA2. Seven
      frameshift and three nonsense mutations were identified, and four mutations are
      novel in the Breast Cancer Information Core. There were no Ashkenazi founder
      mutations detected. The mean age at diagnosis for breast cancer was 33 years. All
      six tumors were infiltrating ductal carcinoma and poorly differentiated.
      Pathologic stage was I or II, and immunohistochemistry showed negative
      immunoreactivity for estrogen receptor and Her-2/neu in all tumors. Positive
      immunoreactivity for progesterone receptor was found only in one tumor. Three
      patients had familial history of breast, ovarian or other cancers. One patient
      who was diagnosed for breast cancer at the age of 26 had two maternal family
      members of metachronous bilateral breast cancer. Another patient who experienced
      metachronous bilateral breast cancer had maternal history of ovarian and
      esophageal cancer. In summary, Korean patients with double heterozygosity for
      BRCA1 and BRCA2 were young at diagnosis of breast cancer. Tumors were early
      stage, high grade, and almost triple-negative phenotype. All familial history of
      breast, ovary or other cancer was maternal. Close surveillance and accurate risk
      assessment should be provided for the patients with mutations in the both of the
      genes.

PMID- 21847644
TI  - The origins of neuromuscular fatigue post-stroke.
AB  - Fatigue post-stroke is a disabling and persistent symptom affecting many stroke
      survivors. Despite its high prevalence, the pathophysiology underlying this
      phenomenon remains obscure. The aim of the present study was to investigate the
      origins of neuromuscular fatigue post-stroke. Ten chronic stroke survivors and 10
      controls sustained an isometric contraction at 30% of maximal voluntary
      contraction (MVC) with the ankle dorsiflexors. Motor evoked potential (MEP),
      cortical silent period (SP), voluntary activation, M wave and contractile
      properties were evaluated before, during and after fatigue among the paretic, non
      paretic and control limbs. The pattern of response to fatigue in the non-paretic
      and control limbs was comparable; therefore, results are presented between the
      paretic and non-paretic limbs. Before fatigue, reduced MVC peak torque and MEP
      amplitude were observed on the paretic side in comparison with the non-paretic
      side. During fatigue, the cortical SP duration increased significantly in both
      limbs, whereas the MEP amplitude significantly increased only in the non-paretic
      limb. After fatigue, MVC peak torque decreased significantly in both limbs.
      Significant reductions in M wave and twitch peak torque were observed in both
      limbs, pointing to the development of peripheral fatigue. However, central
      fatigue, evident by a significant reduction in voluntary activation, was greater
      in the paretic than in the non-paretic limb. After stroke, an inability to
      increase central excitability in response to an increased cortical inhibition
      associated with the fatiguing contraction may contribute to central fatigue
      observed in the paretic limb, which may also be linked to increased self-reported
      fatigue during activities of daily living. These findings advance our
      understanding of the neuromuscular basis of fatigue post-stroke.

PMID- 21847645
TI  - Reactive astrocytosis in feline neonatal hydrocephalus: acute, chronic, and shunt
      induced changes.
AB  - PURPOSE: Reactive astrocytosis has been implicated in injury and recovery
      patterns associated with hydrocephalus. To investigate temporal changes in
      astrogliosis during the early progression of hydrocephalus, after shunting, and
      after long-term ventriculomegaly, glial fibrillary protein (GFAP) levels were
      analyzed in a feline model. METHODS: Obstructive hydrocephalus was induced in 10
      day-old kittens by intracisternal injections of 25% kaolin. Acute non-shunted
      animals were killed 15 days post-kaolin injection to represent the pre-shunt
      condition. Shunt-treated animals received ventriculoperitoneal shunts 15 days
      post-injection and were killed 10 or 60 days later to represent short- and long
      term recovery periods. Chronic untreated animals had Ommaya reservoirs implanted
      15 days post-kaolin, which were tapped intermittently until they were killed 60
      days later. Ventriculomegaly was monitored by neuroimaging before and after
      shunting and at death. RNA and total protein from primary visual cortex were
      analyzed by Northern and Western blotting. RESULTS: GFAP RNA and protein levels
      for acute and chronic non-shunted hydrocephalic animals were 77% and 247% (p <
      0.01) and 659% (p < 0.05) and 871% (p < 0.05) higher than controls, respectively.
      Shunted animals with short-term recovery demonstrated a mismatch in GFAP levels,
      with RNA expression decreasing 26% and protein increasing 335% (p < 0.01).
      Shunted animals with a long-term recovery exhibited GFAP RNA and protein levels
      201% and 357% above normal, respectively. CONCLUSIONS: These results indicate
      that a reactive astrocytic response continues to rise dramatically in chronic
      hydrocephalus, suggesting ongoing gliosis and potential damage. Shunting
      partially ameliorates the continuation of astrogliosis, but does not completely
      reverse this inflammatory reaction even after a long recovery.

PMID- 21847646
TI  - Is influenza A(H1N1) pneumonia more severe than other community-acquired
      pneumonias? Results of the GiViTI survey of 155 Italian ICUs.
AB  - PURPOSE: Uncertainty about the severity of the A(H1N1) pandemia persists.
      Information about disease severity can be obtained by investigating intensive
      care unit (ICU) admissions, especially when historical comparisons can be made
      with cases of community-acquired pneumonia (CAP). METHODS: This prospective
      observational study was conducted in 155 ICUs contributing to the GiViTI national
      database. To assess the impact on ICU workload, the occupancy rate during the
      epidemic phase was compared with influenza periods in previous years. A logistic
      regression model was developed to assess the prognostic importance of A(H1N1)
      influenza. RESULTS: The characteristics of the 319 A(H1N1) cases were similar to
      those reported in other studies, confirming the young age of patients (mean 43
      years) and the higher prevalence among pregnant women and obese people. At the
      epidemic's peak (October-December 2009) the occupancy rate did not significantly
      differ from the same period of the previous year, and was significantly lower
      than the 2009 seasonal influenza outbreak (January-March 2009). Compared with CAP
      of other origin (3,678 patients), A(H1N1) pneumonia was associated with a lower
      risk of death. However, after adjusting for confounding this was no longer the
      case (OR 0.88; 95% CI 0.59-1.31; p = 0.52). CONCLUSION: This study confirmed the
      specific features of critically ill A(H1N1) patients (i.e., young age, pregnancy,
      obesity). The pandemic did not increase ICU workload compared with other periods.
      A(H1N1) pneumonia did not have a higher risk of death than CAP of different
      origin among patients admitted to the ICU.

PMID- 21847647
TI  - Chest compressions versus ventilation plus chest compressions: a randomized trial
      in a pediatric asphyxial cardiac arrest animal model.
AB  - PURPOSE: To compare survival, oxygenation, ventilation, and hemodynamic variables
      achieved with chest compressions or ventilation plus chest compressions. METHODS:
      This randomized experimental study was conducted in the experimental department
      of a university hospital. Thirty infant pigs with asphyxial cardiac arrest were
      randomized into two groups of cardiopulmonary resuscitation (CPR): group 1,
      continuous chest compressions plus non-coordinated ventilation with a mask and
      mechanical ventilator (inspired oxygen fraction 0.21) (VC); group 2, chest
      compressions only (CC). Nine minutes of basic resuscitation was performed
      initially in both groups, followed by advanced resuscitation. CPR was terminated
      on achieving return of spontaneous circulation (ROSC) or after 30 min of total
      resuscitation time without ROSC. RESULTS: Three animals (18.8%) in the VC group
      and 1 (7.1%) in the CC group achieved ROSC (P = 0.351). Oxygenation and
      ventilation during basic CPR were insufficient in both groups, though they were
      significantly better in the VC group than in the CC group after 9 min (PaO(2), 26
      vs. 19 mmHg, P = 0.008; PaCO(2), 84 vs. 101 mmHg, P = 0.05). Cerebral saturation
      was higher in the VC group (61%) than in the CC group (30%) (P = 0.06). There
      were no significant differences in mean arterial pressure. CONCLUSIONS: Neither
      of the basic CPR protocols achieved adequate oxygenation and ventilation in this
      model of asphyxial pediatric cardiac arrest. Chest compressions plus ventilation
      produced better oxygenation, ventilation, and cerebral oxygenation with no
      negative hemodynamic effects. Survival was higher in the VC group, though the
      difference was not statistically significant.

PMID- 21847648
TI  - Microdialysis-assessed interstitium alterations during sepsis: relationship to
      stage, infection, and pathogen.
AB  - PURPOSE: More than a disorder of macrocirculation, sepsis is a disease affecting
      the microcirculation and the tissue metabolism. In vivo microdialysis (MD) is a
      bedside technique that can monitor tissue metabolic changes. We conducted this
      study aiming (1) to assess whether patients at different sepsis stages present
      with different MD-assessed tissue metabolic profiles and (2) to determine if
      different underlying types of infections and implicated pathogens are associated
      with dissimilar metabolic alterations. METHODS: We studied 90 mechanically
      ventilated patients, 65 with septic shock and 25 with severe sepsis. An MD
      catheter was inserted in the subcutaneous adipose tissue of the upper thigh and
      interstitial fluid samples were collected along with arterial blood samples every
      4 h for a maximum of 6 days. Lactate, pyruvate, glycerol, and glucose
      concentrations were measured. RESULTS: During the study period, patients with
      septic shock had higher MD-assessed glycerol (P = 0.009), glycerol gradient (P =
      0.016), and glucose (P = 0.004) than patients with severe sepsis, whereas tissue
      lactate, lactate gradient, and pyruvate dropped significantly with time (P =
      0.007, <0.001, and <0.001, respectively) in both patient groups without any
      observed between-group difference. In addition, there was no between-group
      difference in their tissue lactate/pyruvate ratio on any day, nor did the ratio
      decrease significantly with time. Compared with pneumonia patients, and despite
      similar baseline clinical characteristics, those suffering from intra-abdominal
      infections showed a pattern of higher and progressively increasing tissue levels
      of glucose (P = 0.001) and glycerol (P = 0.001). Finally, patients harboring gram
      positive infections had higher tissue levels of glycerol (P = 0.027) and glycerol
      gradient (P = 0.029) than patients with gram-negative infections. CONCLUSIONS: MD
      can detect tissue metabolic abnormalities that differ in relation to the sepsis
      stage and the type of underlying infection or responsible pathogen. Some of the
      MD-assessed abnormalities are not reflected by conventional blood measurements
      and possess prognostic potential. It remains to be determined if this type of
      metabolic monitoring can find clinical applications in the wide population of
      septic critically ill patients.

PMID- 21847649
TI  - Time course of organ failure in patients with septic shock treated with
      hydrocortisone: results of the Corticus study.
AB  - INTRODUCTION: Corticosteroids have been proposed to decrease morbidity and
      mortality in patients with septic shock. An impact on morbidity should be
      anticipated to be earlier and more easily detected than the impact on mortality.
      METHODS: Prospective, randomized, double-blind, placebo-controlled study of 28
      day mortality in patients with septic shock for <72 h who underwent a short high
      dose ACTH test in 52 centers in 9 European countries. Patients received 11-day
      treatment with hydrocortisone or placebo. Organ dysfunction/failure was
      quantified by the use of the sequential organ failure assessment (SOFA) score.
      RESULTS: From March 2002 to November 2005, 499 patients were enrolled
      (hydrocortisone 251, placebo 248). Both groups presented a similar SOFA score at
      baseline (hydrocortisone 10.8 +/- 3.2 vs. placebo 10.7 +/- 3.1 points). There was
      no difference in 28-day mortality between the two treatment groups
      (hydrocortisone 34.3% vs. placebo 31.5%). There was a decrease in the SOFA score
      of hydrocortisone-treated patients from day 0 to day 7 compared to the placebo
      treated patients (p = 0.0027), driven by an improvement in cardiovascular organ
      dysfunction/failure (p = 0.0005) and in liver failure (p < 0.0001) in the
      hydrocortisone-treated patients. CONCLUSION: Patients randomized to treatment
      with hydrocortisone demonstrated a faster decrease in total organ
      dysfunction/failure determined by the SOFA score, primarily driven by a faster
      improvement in cardiovascular organ dysfunction/failure. This organ
      dysfunction/failure improvement was not accompanied by a decreased mortality.

PMID- 21847650
TI  - Gut mucosal permeability, beta1 receptor blockers and gastric tonometry: the time
      is now!

PMID- 21847651
TI  - Beta-1 blocker improves survival of septic rats through preservation of gut
      barrier function.
AB  - OBJECTIVE: Since recent study demonstrated beneficial effects of beta-adrenergic
      blocker in sepsis, we tested the hypothesis that infusion of selective beta1
      blocker, esmolol, improves outcome in sepsis by modulating inflammatory responses
      and gut barrier function. DESIGN: Prospective randomized animal study. SETTING:
      University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: To
      assess the effects of esmolol infusion on survival time, 19 animals that
      underwent cecal ligation and perforation were randomized into control (n = 9) or
      esmolol (n = 10) groups, the latter of which received esmolol infusion (15
      mg/kg/h) throughout the study period. In an additional 20 animals, levels of
      tumor necrosis factor-alpha (TNF-alpha) in both plasma and intraperitoneal fluid
      were measured, and mesenteric lymph nodes (MLNs) and ileum were excised for
      evaluation of bacterial translocation and mucosal injury at the 18-h study
      period. MEASUREMENTS AND RESULTS: Mean survival time in the esmolol group was
      significantly longer compared with the control group (69.5 +/- 26.8 versus 28.6
      +/- 11.0 h). Plasma TNF-alpha was not detectable in either group, while
      intraperitoneal fluid TNF-alpha level was elevated in the control group but
      significantly depressed in the esmolol group (16.8 +/- 10.7 versus 5.4 +/- 7.1
      pg/ml, P < 0.05). Simultaneously, the Escherichia coli positive rate of MLNs was
      higher (100% versus 44%, P < 0.05) and the gut mucosal injury score was elevated
      (4.1 +/- 0.6 versus 2.8 +/- 0.6, P < 0.01) in the control compared with the
      esmolol group. CONCLUSIONS: Beta-1 blocker therapy improves outcome in sepsis
      possibly through modulation of gut mucosal integrity and local inflammatory
      response.

PMID- 21847652
TI  - Mitochondrial DNA haplogroup R in the Han population and recovery from septic
      encephalopathy.
AB  - PURPOSE: To determine whether the main mitochondrial DNA (mtDNA) haplogroups of
      the Han people are associated with neurological recovery from septic
      encephalopathy. METHODS: We studied 137 individuals with septic encephalopathy
      who were sequentially admitted to the intensive care unit or the emergency
      intensive care unit at the First Affiliated Hospital, College of Medicine,
      Zhejiang University, and the People's Hospital of Zhejiang Province. Demographic
      and clinical data were recorded along with clinical outcome over 28 days. The
      Glasgow coma scale (GCS) score was calculated daily until it reached 15 or until
      the patient died during the 28-day period. Follow-up was completed for all study
      participants. We then determined the mtDNA haplogroups of the patients by
      analyzing sequences of hypervariable mtDNA segments and testing diagnostic
      polymorphisms in the mtDNA coding region with DNA probes. RESULTS: MtDNA
      haplogroup R, one of the main mtDNA haplogroups of the Han people, was a strong
      independent predictor of outcome following septic encephalopathy, conferring a
      4.053-fold (95% CI 1.803-9.110, p = 0.001) increased chance of neurological
      recovery within 28 days compared with those with a non-R mtDNA haplogroup.
      CONCLUSION: In the Han population, mtDNA haplogroup R is a strong independent
      predictor of the outcome of septic encephalopathy, conferring an increased chance
      of neurological recovery compared with individuals with a non-R haplogroup. Our
      results provide potential insights into the mechanisms involved in septic
      encephalopathy, and reveal that the mtDNA haplogroup R is an independent
      predictor of the outcome of septic encephalopathy.

PMID- 21847653
TI  - The Italian version of the Mouth Handicap in Systemic Sclerosis scale (MHISS) is
      valid, reliable and useful in assessing oral health-related quality of life
      (OHRQoL) in systemic sclerosis (SSc) patients.
AB  - In systemic sclerosis (SSc), mouth and face involvement leads to problems in oral
      health-related quality of life (OHRQoL). Mouth Handicap in Systemic Sclerosis
      scale (MHISS) is a 12-item questionnaire specifically quantifying mouth
      disability in SSc, organized in 3 subscales. Our aim was to validate Italian
      version of MHISS, by assessing its test-retest reliability and internal and
      external consistency in Italian SSc patients. Forty SSc patients (7 dSSc, 33
      lSSc; age and disease duration: 57.27 +/- 11.41, 9.4 +/- 4.4 years; 22 with sicca
      syndrome) were evaluated with MHISS. MHISS was translated following a forward
      backward translation procedure, with independent translations and counter
      translation. Test-retest reliability was evaluated, comparing the results of two
      administrations, with intraclass correlation coefficient (ICC). Internal
      consistency was assessed by Cronbach's alpha and external consistency by
      comparison with mouth opening. MHISS has a good test-retest reliability (ICC:
      0.93) and internal consistency (Cronbach's alpha:0.99). A good external
      consistency was confirmed by correlation with mouth opening (rho: -0,3869, p:
      0.0137). Total MHISS score was 17.65 +/- 5.20, with scores of subscale 1 (reduced
      mouth opening) of 6.60 +/- 2.85 and scores of subscales 2 (sicca syndrome) and 3
      (aesthetic concerns) of 7.82 +/- 2.59 and 3.22 +/- 1.14. Total and subscale 2
      scores are higher in dSSc than in lSSc. This result may be due to the higher
      presence of sicca syndrome in dSSc than in lSSc (p = 0.0109). Our results support
      validity and reliability in Italian SSc patients of MHISS, specifically measuring
      SSc OHRQoL.

PMID- 21847655
TI  - JWA enhances As2O3-induced tubulin polymerization and apoptosis via p38 in HeLa
      and MCF-7 cells.
AB  - Arsenic trioxide (As2O3) has potential anti-cancer activity against a wide range
      of carcinomas via apoptosis induction or oncoprotein degradation. The mechanisms
      involved are not fully elucidated. Here, we demonstrated that As2O3 induced
      apoptosis in HeLa and MCF-7 cancer cells was in part triggered by tubulin
      polymerization. High expression of JWA promoted tubulin polymerization and
      increased the sensitivity of the cancer cells to As2O3. The activation of the p38
      MAPK (mitogen-activated protein kinases) signaling pathway was found to
      contribute to JWA-promoted tubulin polymerization. Our results suggest that JWA
      may serve as an effective enhancer of microtubule-targeted As2O3 anti-cancer
      therapy.

PMID- 21847656
TI  - Novel contrast-enhanced ultrasound imaging in prostate cancer.
AB  - PURPOSE: The purposes of this paper were to present the current status of
      contrast-enhanced transrectal ultrasound imaging and to discuss the latest
      achievements and techniques now under preclinical testing. OBJECTIVE: Although
      grayscale transrectal ultrasound is the standard method for prostate imaging, it
      lacks accuracy in the detection and localization of prostate cancer. With the
      introduction of contrast-enhanced ultrasound (CEUS), perfusion imaging of the
      microvascularization became available. By this, cancer-induced neovascularisation
      can be visualized with the potential to improve ultrasound imaging for prostate
      cancer detection and localization significantly. For example, several studies
      have shown that CEUS-guided biopsies have the same or higher PCa detection rate
      compared with systematic biopsies with less biopsies needed. MATERIALS AND
      METHODS: This paper describes the current status of CEUS and discusses novel
      quantification techniques that can improve the accuracy even further.
      Furthermore, quantification might decrease the user-dependency, opening the door
      to use in the routine clinical environment. A new generation of targeted
      microbubbles is now under pre-clinical testing and showed avidly binding to VEGFR
      2, a receptor up-regulated in prostate cancer due to angiogenesis. The first
      publications regarding a targeted microbubble ready for human use will be
      discussed. CONCLUSION: Ultrasound-assisted drug delivery gives rise to a whole
      new set of therapeutic options, also for prostate cancer. A major breakthrough in
      the future can be expected from the clinical use of targeted microbubbles for
      drug delivery for prostate cancer diagnosis as well as treatment.

PMID- 21847657
TI  - Oncologic outcomes following radical prostatectomy with intraoperative cell
      salvage.
AB  - PURPOSE: To evaluate oncologic outcomes following the use of intraoperative cell
      salvage (IOCS) as a blood loss management strategy during open radical
      prostatectomy (RP). METHODS: We retrospectively reviewed all open retropubic RP
      cases performed by a single surgeon. Patients were identified who received IOCS
      blood and evaluated for an increased risk of biochemical recurrence (BCR) and
      overall mortality. RESULTS: The study cohort consisted of 1,862 men, 395 (21.2%)
      of whom received IOCS blood. At a median follow-up of 47.0 months, men who
      received IOCS blood were not at an increased risk of BCR (P = 0.323) or all-cause
      mortality (P = 0.892). IOCS use did not confer an increased risk of BCR within
      any D'Amico preoperative risk category (low risk, P = 0.592; intermediate risk, P
      = 0.107; and high risk, P = 0.697). CONCLUSIONS: IOCS is safe for the management
      of blood loss during RP. At long-term follow-up, IOCS use was not associated with
      an increased risk of BCR or death. While it remains preferable to avoid any form
      of blood transfusion, we advocate for the use of IOCS in place of allogeneic
      blood. These conclusions are drawn from our study of the largest and longest
      followed cohort patients who received IOCS blood during RP.

PMID- 21847658
TI  - The clinical impact of pathological review on selection the treatment modality
      for localized prostate cancer in candidates for brachytherapy monotherapy.
AB  - AIM: To evaluate the impact of pathological review by pathologist with
      genitourinary expertise (PGU) on treatment modality of localized prostate cancer,
      we analyzed Gleason grade (GG) migration and the final treatment decision in a
      cohort of patients designated for permanent prostate brachytherapy (PPB).
      METHODS: From February 2005 to July 2010, a total of 247 patients with localized
      prostate cancer diagnosed by local community hospitals were referred to our
      hospital for PPB monotheray. All pathologic slides of prostate biopsies were
      reviewed by a single PGU. Patients ultimately selected their treatment modality
      from our recommendations based on the review. Indication for PPB monotherapy was
      the NCCN classification of patients as good or intermediate risk. In addition,
      patient with Primary GG 4 was regarded as unadapted case. RESULTS: Six cases were
      reinterpreted as no cancer (2.4%). GG change occurred in 94 cases (38.1%) of
      which 77 (81.9%) were upgraded and 17 (18.1%) downgraded. Of the total 247
      patients, 86 (34.8%) changed therapies and 30 (12.1%) did so based on the
      pathologic slide review. CONCLUSIONS: Pathological review of biopsy specimens is
      mandatory for the determination of treatment modality especially in candidates
      for monotherapy of permanent prostate brachytherapy.

PMID- 21847660
TI  - Mercury, selenium and neurochemical biomarkers in different brain regions of
      migrating common loons from Lake Erie, Canada.
AB  - Common loons (Gavia immer) can be exposed to relatively high levels of dietary
      methylmercury (MeHg) through fish consumption, and several studies have
      documented MeHg-associated health effects in this species. To further study the
      neurological risks of MeHg accumulation, migrating loons dying of Type E botulism
      were collected opportunistically from the Lake Erie shore at Long Point (Ontario,
      Canada) and relationships between total mercury (THg), selenium (Se), and
      selected neurochemical receptors and brain enzymes were investigated. THg
      concentrations were 1-78 MUg/g in liver; and 0.3-4 MUg/g in the brain (all
      concentrations reported on a dry weight basis). A significant (p < 0.05) positive
      correlation was found between THg in liver and THg in 3 subregions of the brain
      (cerebral cortex: r = 0.433; cerebellum: r = 0.293; brain stem: r = 0.405). THg
      varied significantly among different brain regions, with the cortex having the
      highest concentrations. Se levels in the cortex and cerebellum were 1-29 and 1-10
      MUg/g, respectively, with no significant differences between regions. Se was not
      measured in brain stem due to insufficient tissue mass. There were molar excesses
      of Se over mercury (Hg) in both cortex and cerebellum at all Hg concentrations,
      and a significant positive relationship between THg and the Hg:Se molar ratio
      (cortex: r = 0.63; cerebellum: r = 0.47). No significant associations were
      observed between brain THg and the N-methyl-D-aspartic acid (NMDA) receptor
      concentration, nor between THg and muscarinic cholinergic (mACh) receptor
      concentration; however, brain THg levels were lower than in previous studies that
      reported significant Hg-associated changes in neuroreceptor densities. Together
      with previous studies, the current findings add to our understanding of Hg
      distribution in the brain of common loons, and the associations between Hg and
      sub-lethal neurochemical changes in fish-eating wildlife.

PMID- 21847659
TI  - Immunotoxic effects of triclosan in the clam Ruditapes philippinarum.
AB  - The effects of Triclosan (TCS) on the immune parameters of the clam Ruditapes
      philippinarum were investigated after a 7-day exposure to sublethal TCS
      concentrations (300, 600, and 900 ng l(-1)). Hemocytes from controls and exposed
      clams were collected, and the effects of TCS on total hemocyte count (THC),
      hemocyte diameter and volume, uptake of the vital dye Neutral Red (an indicator
      of pinocytosis), lysozyme activity, and proliferation were evaluated. The
      cytotoxicity, which was evaluated using the lactate dehydrogenase assay, and the
      capability of TCS to induce DNA fragmentation, which indicated apoptosis, were
      also investigated. The exposure of clams to all tested TCS concentrations
      significantly decreased THC, whereas the highest tested TCS concentration
      significantly reduced the diameter and volume of hemocytes. TCS negatively
      affected pinocytosis and the proliferation of hemocytes, but it did not alter
      hemocyte lysozyme activity. TCS exerted cytotoxic effects and induced DNA
      fragmentation in hemocytes of R. philippinarum. Overall, these results suggest a
      relationship between TCS exposure and changes in the measured immune parameters
      and indicate immunosuppression in TCS-treated clams.

PMID- 21847661
TI  - (E)-beta-farnesene synthase genes affect aphid (Myzus persicae) infestation in
      tobacco (Nicotiana tabacum).
AB  - Aphids are major agricultural pests which cause significant yield losses of the
      crop plants each year. (E)-beta-farnesene (EbetaF) is the alarm pheromone
      involved in the chemical communication between aphids and particularly in the
      avoidance of predation. In the present study, two EbetaF synthase genes were
      isolated from sweet wormwood and designated as AabetaFS1 and AabetaFS2,
      respectively. Overexpression of AabetaFS1 or AabetaFS2 in tobacco plants resulted
      in the emission of EbetaF ranging from 1.55 to 4.65 ng/day/g fresh tissues.
      Tritrophic interactions involving the peach aphids (Myzus persicae), predatory
      lacewings (Chrysopa septempunctata) demonstrated that the transgenic tobacco
      expressing AabetaFS1 and AabetaFS2 could repel peach aphids, but not as strongly
      as expected. However, AabetaFS1 and AabetaFS2 lines exhibited strong and
      statistically significant attraction to lacewings. Further experiments combining
      aphids and lacewing larvae in an octagon arrangement showed transgenic tobacco
      plants could repel aphids and attract lacewing larvae, thus minimizing aphid
      infestation. Therefore, we demonstrated a potentially valuable strategy of using
      EbetaF synthase genes from sweet wormwood for aphid control in tobacco or other
      economic important crops in an environmentally benign way.

PMID- 21847663
TI  - Generalized stern models of the electric double layer considering the spatial
      variation of permittvity and finite size of ions in saturation regime.
AB  - The interaction between a charged metal implant surface and a surrounding body
      fluid (electrolyte solution) leads to ion redistribution and thus to formation of
      an electrical double layer (EDL). The physical properties of the EDL contribute
      essentially to the formation of the complex implant-biosystem interface. Study of
      the EDL began in 1879 by Hermann von Helmholtz and still today remains a
      scientific challenge. The present mini review is focused on introducing the
      generalized Stern theory of an EDL, which takes into account the orientational
      ordering of water molecules. To ascertain the plausibility of the generalized
      Stern models described, we follow the classical model of Stern and introduce two
      Langevin models for spatial variation of the relative permittivity for point-like
      and finite sized ions. We attempt to uncover the subtle interplay between water
      ordering and finite sized ions and their impact on the electric potential near
      the charged implant surface. Two complementary effects appear to account for the
      spatial dependency of the relative permittivity near the charged implant surface 
      the dipole moment vectors of water molecules are predominantly oriented towards
      the surface and water molecules are depleted due to the accumulation of
      counterions. At the end the expressions for relative permittivity in both
      Langevin models were generalized by also taking into account the cavity and
      reaction field.

PMID- 21847662
TI  - Role of lipid droplet proteins in liver steatosis.
AB  - Five proteins of the perilipin (Plin) family such as Plin1 (perilipin) Plin2
      (adipose differentiation-related protein), Plin3 (tail-interacting protein of 47
      kDa), Plin4 (S3-12), and Plin5 (myocardial lipid droplet protein) are
      characterized as lipid droplet (LD) proteins in adipocytes. Recent reports have
      demonstrated that fat-specific protein 27 (FSP27) and hypoxia-inducible protein 2
      (HIG2) are also thought to be novel LD proteins in addition to proteins of the
      Plin family. Growing evidence have shown that LD proteins play a role in the
      pathophysiology in the fatty liver disease which is characterized by hepatocytes
      containing LD with excessive neutral lipid. Studies showed LD proteins such as
      Plin1, Plin2, Plin3, Plin5, FSP27, and HIG2 are expressed in the liver steatosis.
      Among them, a high fat diet increases expression of Plin2 and/or FSP27 through
      activation of peroxisome proliferator-activated receptor gamma to develop fatty
      liver. In this article, recent advances on the role of LD proteins in
      pathophysiology of fatty liver diseases are summarized.

PMID- 21847664
TI  - 17beta-Estradiol promotes cell proliferation in rat osteoarthritis model
      chondrocytes via PI3K/Akt pathway.
AB  - Osteoarthritis (OA) is the most common cause of musculoskeletal pain and
      disability. The importance of chondrocytes in the pathogenesis of OA is
      unequivocal. 17beta-estradiol (E2) has a potential protective effect against OA.
      However, the mechanism of E2 in OA chondrocytes remains unclear. In this study,
      we investigated the regulative effect of E2 on cell growth and the relationship
      between E2 and the PI3K/Akt pathway in rat OA model chondrocytes (pretreated with
      interleukin-1beta). We found that E2 induced chondrocyte proliferation, and
      increased the expression level of Akt simultaneously, especially the expression
      level of P-Akt. Furthermore, the inhibition of P-Akt could block chondrocyte
      proliferation induced by E2. These results suggest that PI3K/Akt activation
      induced by E2 may be an important factor in the mechanism of E2 in cell
      proliferation in rat OA model chondrocytes, and help further understanding the
      role of E2 in OA progression.

PMID- 21847666
TI  - Evaluation of normal appearing white matter in multiple sclerosis: comparison of
      diffusion magnetic resonance, magnetization transfer imaging and multivoxel
      magnetic resonance spectroscopy findings with expanded disability status scale.
AB  - PURPOSE: The aim of this study was to determine diffusion magnetic resonance
      imaging (MRI), magnetization transfer (MT) imaging and multivoxel MR spectroscopy
      findings in plaques, periplaque white matter and normal appearing white matter
      (NAWM) regions in multiple sclerosis (MS) and to correlate the findings with the
      expanded disability status scale (EDSS). METHODS: A total of 30 patients with MS
      and 30 healthy control subjects were studied and apparent diffusion coefficient
      (ADC) values, MT ratio (MTR), N-acetyl-aspartate/creatine (NAA/Cr) and
      choline/creatine (Cho/Cr) ratios were measured in plaques, periplaques and NAWM
      regions and compared with the control subjects. RESULTS: The MTR and NAA/Cr ratio
      were decreased more in plaques than periplaques and NAWM, in contrast ADC values
      and Cho/Cr ratios were highest in plaques and higher in periplaques than in NAWM.
      Decreased MTR and NAA/Cr in NAWM demonstrated moderate inverse correlations (r = 
      0.604, p < 0.001 and r = - 0.494, p < 0.001, respectively) while Cho/Cr ratios
      and ADC of NAWM demonstrated weak linear correlations (r = 0.370, p = 0.004, r =
      0.297, p = 0.021 respectively) with EDSS. CONCLUSIONS: The MS, MTR and MR
      spectroscopy findings were found to be useful for detecting subtle abnormalities
      in NAWM. Although ADC values were significantly altered in plaque and periplaque
      regions a significance difference was not found in NAWM.

PMID- 21847667
TI  - siRNA-mediated inhibition of Na(+)-K(+)-2Cl- cotransporter (NKCC1) and regulatory
      volume increase in the chondrocyte cell line C-20/A4.
AB  - The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is an essential membrane transporter
      and has been linked to the regulation of volume, matrix synthesis and bone growth
      in chondrocytes; the sole resident cell type of articular cartilage. Despite the
      integral nature of NKCC1, its regulation is currently poorly understood, and
      therefore here we describe a NKCC1 knockdown technique that will permit the
      easier study of this transporter. Small interfering RNA (siRNA), designed to
      knock down NKCC1, was transfected into the chondrocyte cell line C-20/A4 and the
      efficacy determined at the message, protein and functional levels. NKCC1
      expression was analyzed by reverse-transcriptase polymerase chain reaction, where
      NKCC1 expression declined to 25.10 +/- 1.08% after 12 h of transfection and did
      not show any rise in the following 36 h. The efficacy of the designed siRNA
      molecules was confirmed by both Western blot and immunocytochemistry. The effect
      of the knockdown on regulatory volume increase (RVI, a novel assay for NKCC1
      function) was investigated by confocal laser scanning microscopy in response to a
      43% hypertonic challenge, whereby control chondrocytes underwent a decrease in
      volume to 67.38 +/- 1.70%, followed by volume restoration to 82.17 +/- 2.23 at 20
      min (t1/2 = 22.11 +/- 3.23 min). Conversely, upon knockdown, chondrocytes
      exhibited a slower rate of RVI (t1/2 = 43.26 +/- 5.64 min), thus suggesting that
      NKCC1 plays an important and yet partial role in RVI in C-20/A4 chondrocytes.
      Together, these data provide a robust protocol for the study of NKCC1 in
      chondrocytes and suggest a mechanism for C-20/A4 chondrocyte RVI.

PMID- 21847668
TI  - Effects of furanocoumarins from apiaceous vegetables on the catalytic activity of
      recombinant human cytochrome P-450 1A2.
AB  - Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens
      may be an important chemopreventive mechanism. Consumption of apiaceous
      vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many
      furanocoumarins are potent inhibitors of several CYPs, we characterized the
      effects of three furanocoumarins from apiaceous vegetables on human CYP1A2
      (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity
      using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin
      exhibited mechanism-based inactivation (MBI) of hCYP1A2 (K(i) = 1.2 MUM, k
      (inact) = 0.34 min-1, and partition ratio = 8). Imperatorin and trioxsalen were
      characterized as mixed inhibitors with K(i) values of 0.007 and 0.10 MUM,
      respectively. These results indicate that even if present at low levels in
      apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute
      significantly to CYP1A2 inhibition and potentially decreased procarcinogen
      activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be
      longer lasting compared to reversible inhibitors.

PMID- 21847669
TI  - Colorado alphaherpesvirus latency symposium.

PMID- 21847670
TI  - Children's views on unlicensed/off-label paediatric prescribing and paediatric
      clinical trials.
AB  - OBJECTIVES: To explore the views and perspectives of children on the
      unlicensed/off-label use of medicines in children and on the participation of
      children in clinical trials. METHODS: Focus-group discussions, involving school
      children, were carried out in a range of primary and secondary schools in
      Northern Ireland. A purposeful sample was chosen to facilitate representation of
      various socioeconomic groupings. RESULTS: A total of 123 pupils, aged from 10 to
      16 years, from six schools, participated in 16 focus groups. In general, pupils
      viewed the unlicensed/off-label use of medicines in children as unsafe and
      unethical and felt it is necessary to test medicines in children to improve the
      availability of licensed products. The majority felt that older children should
      be told, and that parents should be told, about the unlicensed/off-label use of
      medicines in children, yet they recognised some implications of this, such as
      potential medication non-adherence. CONCLUSIONS: This is the first study to
      explore the views of healthy children on unlicensed medicine use in children.
      Children were able to recognise potential risks associated with the unlicensed
      use of medicines and felt it is necessary to test and license more medicines in
      children. PRACTICE IMPLICATIONS: Health care professionals should consider the
      views of children in decisions that affect their health.

PMID- 21847672
TI  - Characteristics and determinants of music appreciation in adult CI users.
AB  - The main objective of this study was to assess the associations between self
      reported listening habits and perception of music and speech perception outcomes
      in quiet and noise for both unilateral cochlear implant (CI) users and bimodal
      (CI in one ear, hearing aid in contra-lateral ear) users. Information concerning
      music appreciation was gathered by means of a newly developed questionnaire.
      Moreover, audiological data (pure-tone audiometry, speech tests in noise and
      quiet) were gathered and the relationship between speech perception and music
      appreciation is studied. Bimodal users enjoy listening to music more in
      comparison with unilateral CI users. Also, music training within rehabilitation
      is still uncommon, while CI recipients believe that music training might be
      helpful to maximize their potential with current CI technology. Music training
      should not be exclusively reserved for the good speech performers. Therefore, a
      music training program (MTP) that consists of different difficulty levels should
      be developed. Hopefully, early implementation of MTP in rehabilitation programs
      can enable adult CI users to enjoy and appreciate music and to maximize their
      potential with commercially available technology. Furthermore, because bimodal
      users consider the bimodal stimulation to be the most enjoyable way to listen to
      music, CI users with residual hearing in the contra-lateral ear should be
      encouraged to continue wearing their hearing aid in that ear.

PMID- 21847673
TI  - High ear-piercing: an increasingly popular procedure with serious complications.
      Is good clinical practice exercised?
AB  - This study aimed to explore the current practice of performing high ear-piercing
      regarding consent protocols, and methods of practice using questionnaire-based
      survey in Hertfordshire and North London. Recommendations for good clinical
      practice are also made. 100 establishments performing ear piercing were
      identified. A 16-item questionnaire on techniques used, methods of high-ear
      piercing, methods of sterilization, consent issues and aftercare was completed.
      Seventy-six establishments agreed to participate. All practitioners prepared the
      skin before piercing. 58 (76%) used a needle for piercing, 11 (15%) used a spring
      loaded gun and seven (9%) used both. 97% of the practitioners obtained written
      consent before proceeding. 9 (12%) had a lower age limit of 16 years and three
      (4%) of 18 years. 27 piercers (36%) provided an aftercare leaflet, 41 (54%)
      warned the patients about risks of infection, 16 (21%) warned about cosmetic
      deformity and 1 (1%) specifically mentioned cauliflower ear. Results indicated
      that high ear piercing is an invasive procedure with a significant risk of
      complications leading to cosmetic deformity. Establishments should be required to
      counsel patients properly about the risks and potential complications of the
      procedure. A code of practice should be drawn up with a minimum age for piercing,
      requirement for proper consent, excellent hygiene and good information for
      postoperative care.

PMID- 21847674
TI  - Engineered mammalian vector to express EGFP-tagged proteins as biomarkers.
AB  - Due to its specialized post-translational machinery, mammalian cells represent an
      interesting and not fully explored system to express snake toxins. Therefore, in
      this work, we built up a new mammalian expression vector that enhances the
      feasibility to use mammalian cells to express proteins as biomarkers. Among the
      modifications, an Igkappa signal peptide and a 6xHis tag were inserted into this
      vector in order to drive the protein to the supernatant and simplify its
      purification, respectively. In addition, to facilitate selection of high
      producing clones and also tag proteins which may function as a biomarker, the
      sequence of enhanced green fluorescent protein (EGFP) was added. The efficiency
      of the resulting vector (pToxEGFP) was tested by cloning and expressing the viper
      venom disintegrin echistatin (Ech) that due to its affinity to integrin
      alphavbeta3 was tested as a molecular marker. Expression of EGFP-Ech was achieved
      in CHO-DXB11 cells resulting in a yield of 22 mg/L. The binding activity of this
      chimera protein was successfully achieved on human umbilical vein endothelial
      cells which highly express alphavbeta3. The results indicate that pToxEGFP may
      constitute an efficient and versatile expression vector to express tagged
      proteins with potential biomarker activity.

PMID- 21847675
TI  - Promoter polymorphisms of the HLA-G gene, but not the HLA-E and HLA-F genes, is
      associated with non-segmental vitiligo patients in the Korean population.
AB  - The aim of this study was to determine whether or not promoter polymorphisms of
      the class I major histocompatibility complex (HLA-E, HLA-F, and HLA-G) are
      associated with susceptibility to vitiligo. To identify a possible association
      with vitiligo, 241 patients with non-segmental vitiligo (NSV) and 395 healthy
      controls were recruited in this study. Three promoter single nucleotide
      polymorphisms (SNPs; rs1264459 of HLA-E, rs9258170 of HLA-F, and rs1736936 of HLA
      G) were analyzed using a polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) technique and direct sequencing. Multiple logistic
      regression models (co-dominant 1, co-dominant 2, dominant, recessive, and log
      additive models) were applied for odds ratios (ORs), 95% confidence intervals
      (CIs), and P values. To obtain the defined results, P values were recalculated by
      a Bonferroni correction. After the Bonferroni correction, the genotype of the SNP
      (rs1736936) of HLA-G was shown to have significant association with NSV (P =
      0.045 in the recessive model). The genotype frequencies of the HLA-G SNP
      (rs1736936) had a significant correlation with the age of onset of NSV (P = 0.016
      in the co-dominant 1 model and P = 0.027 in the dominant model). Our results
      suggest that HLA-G, but not HLA-E and HLA-F, may be associated with
      susceptibility to NSV in the Korean population.

PMID- 21847676
TI  - Maternity care practices and breastfeeding experiences of women in different
      racial and ethnic groups: Pregnancy Risk Assessment and Monitoring System
      (PRAMS).
AB  - Research shows that maternity care practices are important to promoting
      breastfeeding in the early post partum period; however, little is known about the
      association between maternity care practices and breastfeeding among different
      racial and ethnic groups. We examined the association between maternity care
      practices and breastfeeding duration to >=10 weeks overall and among various
      racial and ethnic groups using data from the Pregnancy Risk Assessment and
      Monitoring System (PRAMS). PRAMS is a state, population-based surveillance system
      that collects information on maternal behaviors. We used maternity care practices
      data from 11 states and New York City with response rates >=70% from 2004 to
      2006. Multiple maternity care practices were examined and the analysis adjusted
      for demographic characteristics, participation in the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC), lifestyle, and infant
      variables. The outcome variable for multivariable analysis was breastfeeding
      duration to <10 weeks or >=10 weeks. PRAMS data show that 22.1% of women did not
      breastfeed, about 27.7% breastfed for <10 weeks and 50.2% breastfed for >=10
      weeks. Breastfeeding patterns varied with white and Hispanic women reporting
      highest breastfeeding initiation and duration prevalence. Overall, practices
      positively associated with >=10 duration were: breastfeeding initiated within the
      first hour after birth (adjusted OR [AOR] = 1.29; 95% CI: 1.16-1.45); fed breast
      milk only (AOR = 2.40; 95% CI: 2.15-2.68); breastfed on demand (AOR = 1.23; 95%
      CI 1.08-1.40) and receiving telephone support (AOR = 1.20; 95% CI: 1.03-1.39).
      Maternity care practices associated with breastfeeding to >=10 weeks varied
      across three racial/ethnic groups. One practice, that of giving newborns breast
      milk only, was positively associated with breastfeeding duration of >=10 weeks
      across all three groups. Maternity care practices associated with breastfeeding
      continuation to >=10 weeks varied by race/ethnicity. For example: breastfeeding
      within the first hour, baby given a pacifier, and assistance from hospital staff,
      were significantly associated with breastfeeding duration among black and white
      women and not Hispanics. The practice of breastfeeding on demand was
      significantly associated with breastfeeding to >=10 weeks for black and Hispanic
      women and not for whites. Hospitals may want to examine the implementation of
      specific practices in relation to the cultural backgrounds of women to promote
      breastfeeding.

PMID- 21847677
TI  - The association between maternal oral health experiences and risk of preterm
      birth in 10 states, Pregnancy Risk Assessment Monitoring System, 2004-2006.
AB  - The aim of this study is to investigate the association between oral health
      experiences of women in the peripartum period and the risk of preterm delivery
      (<37 weeks). We analyzed 2004-2006 data from the CDC Pregnancy Risk Assessment
      Monitoring System (PRAMS), a population-based surveillance system that collects
      data on pregnancy and postpartum experiences of mothers who have recently
      delivered a live infant. Ten states included in the analysis had a >=70% weighted
      response rate and three standard questions pertaining to oral health. White non
      Hispanic (WNH), Black non-Hispanic (BNH), and Hispanic women were selected for
      analysis. Chi-squared analysis was performed for our bivariate analysis and
      multivariate logistic regression models were created to calculate adjusted odds
      ratios, controlling for socio-demographic characteristics and peripartum
      morbidities. Weighted percentages and standard errors were used for all analyses.
      Among the 35,267 women studied, in the multivariate analysis, mothers who did not
      receive dental care during pregnancy and did not have a teeth cleaning during
      pregnancy were at higher risk for delivering a preterm infant (OR 1.15, CI 1.02
      1.30; OR 1.23, CI 1.08-1.41). In this population-based study, women who did not
      receive dental care or have a teeth cleaning during pregnancy were at slightly
      higher risk for preterm delivery after adjustment for pertinent confounders.

PMID- 21847680
TI  - Closed platysmotomy: a new procedure for the treatment of platysma bands without
      skin dissection.
AB  - Platysma muscular bands are present during the aging period, generally starting
      in the second half of the fourth decade of life in both sexes. One or two bands
      along the anterior segment of the neck are the most frequent, with varied
      extensions and appearances. The literature records different techniques for
      solving the problem of platysma bands. All the methods involve submental
      incision, cutaneous dissection, and various tactics for eliminating the action of
      the platysma bands. This report aims to describe a procedure for deactivating
      these bands using a percutaneous approach that eliminates the need for submental,
      cutaneous incision and dissection. This technique involves the use of a steel
      wire loop that encircles the platysma band and is connected to a device known as
      the platysmotome through two puncture holes in the skin. Three to six sections
      along each band eliminate the platysma band, leaving no visible marks on the
      skin. This method is indicated as an isolated procedure for patients with visible
      platysma bands and no skin flaccidity, patients with recurring bands after face
      lifting and no cervical skin flaccidity, patients who have bands with little
      cervical skin flaccidity but do not care to undergo face-lifting, and patients
      who undergo face-lifts for platysma bands that include closed platysmotomy and
      tightening of the platysma by lateral suture. The described technique is a method
      specifically designed for deactivation of the platysma bands that can be used
      both in isolation and in conjunction with face-lifting. Because this method
      avoids submental, cervical incision and dissection, it is a less invasive
      technique for "deleting" the bands, whether applied alone or in association with
      face-lifting. From May 2008 to November 2009 (19 months), 61 patients underwent
      surgery for the correction of platysma bands via percutaneous myotomy. Among
      them, the first 11 patients received postoperative follow-up evaluation ranging
      from 8 to 17 months.

PMID- 21847678
TI  - Corneal collagen cross-linking using riboflavin and ultraviolet-A irradiation: a
      review of clinical and experimental studies.
AB  - Corneal collagen cross-linking (CXL) using riboflavin and ultraviolet-A
      irradiation is a common method of tissue stabilization and has been developed
      primarily to address the need of treating keratoconus. CXL's promising results on
      keratoconus indicated that it might be effective in other corneal diseases as
      well. This new treatment promises a slowing effect on the progression of these
      diseases and its initial results show that it is safe and reasonably curative.
      The purpose of this review is to critically evaluate this treatment, to explore
      its benefits, to highlight its limitations in terms of efficacy and long-term
      safety and finally to identify areas for future research in this topic with a
      significant potential to change the way we treat our patients. In addition, in
      this unbiased review we try to bring together all the scientific information from
      both laboratory and clinical trials that have been conducted during recent years
      and to review the most recent publications regarding the therapeutic indications
      of CXL.

PMID- 21847681
TI  - Gene expression profiling reveals differential effects of sodium selenite,
      selenomethionine, and yeast-derived selenium in the mouse.
AB  - The essential trace mineral selenium is an important determinant of oxidative
      stress susceptibility, with several studies showing an inverse relationship
      between selenium intake and cancer. Because different chemical forms of selenium
      have been reported to have varying bioactivity, there is a need for nutrigenomic
      studies that can comprehensively assess whether there are divergent effects at
      the molecular level. We examined the gene expression profiles associated with
      selenomethionine (SM), sodium selenite (SS), and yeast-derived selenium (YS) in
      the intestine, gastrocnemius, cerebral cortex, and liver of mice. Weanling mice
      were fed either a selenium-deficient (SD) diet (<0.01 mg/kg diet) or a diet
      supplemented with one of three selenium sources (1 mg/kg diet, as either SM, SS
      or YS) for 100 days. All forms of selenium were equally effective in activating
      standard measures of selenium status, including tissue selenium levels,
      expression of genes encoding selenoproteins (Gpx1 and Txnrd2), and increasing
      GPX1 enzyme activity. However, gene expression profiling revealed that SS and YS
      were similar (and distinct from SM) in both the expression pattern of individual
      genes and gene functional categories. Furthermore, only YS significantly reduced
      the expression of Gadd45b in all four tissues and also reduced GADD45B protein
      levels in liver. Taken together, these results show that gene expression
      profiling is a powerful technique capable of elucidating differences in the
      bioactivity of different forms of selenium.

PMID- 21847682
TI  - [Expression of the tumormarker p16INK4a in cytology specimens of the urinary
      bladder. A new means for early recognition and surveillance of urothelial
      cancer].
AB  - BACKGROUND: This study was carried out to learn whether cytological specimens
      from urinary bladder lavages express the tumor suppressor gene p16INK4a, whether
      an abnormally increased expression indicates a cancerous state and whether
      cytological measurements are comparable regarding sensitivity and specificity
      with measurements made in histological sections of biopsies. PATIENTS AND
      METHODS: A total of 82 urine specimens of patients suspected of having a bladder
      tumor were examined for the presence of p16INK4a. RESULTS: Out of 46 patients
      with urothelial carcinoma 29 expressed p16INK4a in the cells in the urine
      specimens. Out of 36 patients free of cancer 30 expressed no p16INK4a in
      cytological specimens. The sensitivity of the expression proved to be 63% and the
      specificity 83%. Well-differentiated carcinomas seldomly expressed an increased
      p16INK4a (sensitivity 27%), whereas moderately differentiated carcinomas showed a
      sensitivity of 69% and poorly differentiated carcinomas a sensitivity of 77%.
      CONCLUSION: Compared to other minimally invasive tumor markers, such as NMP22,
      the expression of p16INK4a in cytology specimens of urine appears to be a
      sensitive marker for urothelial carcinoma, especially for the detection of poorly
      differentiated carcinomas. Its high specificity makes it ideal for use in tumor
      screening.

PMID- 21847683
TI  - Re: Risk factors for stroke during surgery for carotid body tumors.

PMID- 21847684
TI  - Surgical strategies for management of the open abdomen.
AB  - Since the mid-1990s the surgical community has seen a surge in the prevalence of
      open abdomens (OAs) reported in the surgical literature and in clinical practice.
      The OA has proven to be effective in decreasing mortality and immediate
      postoperative complications; however, it may come at the cost of delayed
      morbidity and the need for further surgical procedures. Indications for leaving
      the abdomen open have broadened to include damage control surgery, abdominal
      compartment syndrome, and abdominal sepsis. The surgical options for management
      of the OA are now more diverse and sophisticated, but there is a lack of
      prospective randomized controlled trials demonstrating the superiority of any
      particular method. Additionally, critical care strategies for optimization of the
      patient with an OA are still being developed. Review of the literature suggests a
      bimodal distribution of primary closure rates, with early closure dependent on
      postoperative intensive care management and delayed closure more affected by the
      choice of the temporary abdominal closure technique. Invariably, a small fraction
      of patients requiring OA management fail to have primary fascial closure and
      require some form of biologic fascial bridge with delayed ventral hernia repair
      in the future.

PMID- 21847685
TI  - Laser ablation imparts controlled micro-scale pores in electrospun scaffolds for
      tissue engineering applications.
AB  - Electrospun scaffolds have been used extensively for tissue engineering
      applications due to the simple processing scheme and versatility. However, many
      additional benefits can be imparted to these materials via post-processing
      techniques. Specifically the addition of structured pores on the micro-scale can
      offer a method to enable patterned cell adhesion, enhanced diffusional
      properties, and/or guide vascular infiltration upon implantation in vivo. In this
      study, we laser ablated electrospun poly(L: -lactic acid) (PLA) scaffolds and
      assessed the ablation process and cellular interaction by examining human adipose
      derived stem cell (hASC) viability and proliferation on laser micro-machined
      scaffolds. Laser ablated pores of 150, 300, and 600 MUm diameter were micro
      machined through electrospun PLA scaffolds. Laser ablation parameters were varied
      and it was determined that the aperture and z-travel direction of the laser
      linearly correlated with the ablated pore diameter. To assess cytocompatibility
      of the micro-machined scaffolds, hASCs were seeded on each scaffold and cell
      viability was assessed on day 7. Human ASCs were able to adhere around the micro
      machined features. DNA content was quantified on all scaffolds and it was
      determined that hASCs were able to proliferate on all scaffolds. The process of
      laser ablation could impart many beneficial features to electrospun scaffolds by
      increasing mass transport and mimicking micro-scale features and assisting in
      patterning of cells around micro-machined features.

PMID- 21847687
TI  - Role of the hospital pharmacy and therapeutics committee in detecting and
      regulating off-label drug use.

PMID- 21847688
TI  - Platyconic acid, a saponin from Platycodi radix, improves glucose homeostasis by
      enhancing insulin sensitivity in vitro and in vivo.
AB  - BACKGROUND: Previous research demonstrated that the crude saponins of Platycodi
      radix improve glucose metabolism by enhancing insulin sensitivity in type 2
      diabetic animals; however, which individual saponins are the most potent insulin
      sensitizers is unknown. OBJECTIVES: This study investigated which saponin(s) have
      anti-diabetic action in vitro and in vivo. METHODS: The insulin-stimulated
      glucose uptake and PPAR-gamma agonistic actions of six saponins from Platycodi
      radix were investigated in 3T3-L1 adipocytes, and glucose-stimulated insulin
      secretion was determined in Min6 cells. Four individual saponins (20 mg/kg body
      weight) were orally administered to low-dose streptozotocin-injected diabetic
      mice fed a high-fat diet for 8 weeks to evaluate glucose tolerance by oral
      glucose tolerance testing (OGTT), insulin sensitivity by insulin tolerance
      testing, and insulin signaling in the liver and adipose tissues. RESULTS:
      Platyconic acid (PA) most effectively increased insulin-stimulated glucose uptake
      in 3T3-L1 adipocytes, possibly in part by working as a peroxisome proliferator
      activated receptors (PPAR)-gamma activator; however, none of the saponins
      improved glucose-stimulated insulin secretion in insulinoma cells. PA-treated
      diabetic mice exhibited the lowest peak serum glucose levels and highest serum
      insulin levels during the first part of OGTT. PA also improved insulin
      sensitivity: PA increased glycogen accumulation and decreased triacylglycerol
      storage in liver, which was associated with enhanced hepatic insulin signaling,
      while PA potentiated the expression of adiponectin and PPAR-gamma in adipose
      tissue, and improved insulin signaling and increased GLUT4 translocation into the
      membranes. CONCLUSIONS: PA improves glucose homeostasis in type 2 diabetic mice,
      partly by enhancing hepatic and adipocyte insulin sensitivity, possibly by
      activating PPAR-gamma.

PMID- 21847689
TI  - Quantitative PK-PD model-based translational pharmacology of a novel kappa opioid
      receptor antagonist between rats and humans.
AB  - Pharmacokinetic-pharmacodynamic (PK-PD) modeling greatly enables quantitative
      implementation of the "learn and confirm" paradigm across different stages of
      drug discovery and development. This work describes the successful prospective
      application of this concept in the discovery and early development of a novel
      kappa-opioid receptor (KOR) antagonist, PF-04455242, where PK-PD understanding
      from preclinical biomarker responses enabled successful prediction of the
      clinical response in a proof of mechanism study. Preclinical data obtained in
      rats included time course measures of the KOR antagonist (PF-04455242), a KOR
      agonist (spiradoline), and a KOR-mediated biomarker response (prolactin
      secretion) in plasma. Clinical data included time course measures of PF-04455242
      and prolactin in 24 healthy volunteers following a spiradoline challenge and
      single oral doses of PF-04455242 (18 and 30 mg). In both species, PF-04455242
      successfully reversed spiradoline-induced prolactin response. A competitive
      antagonism model was developed and implemented within NONMEM to describe the
      effect of PF-04455242 on spiradoline-induced prolactin elevation in rats and
      humans. The PK-PD model-based estimate of K(i) for PF-04455242 in rats was 414
      ng/mL. Accounting for species differences in unbound fraction, in vitro K(i) and
      brain penetration provided a predicted human K(i) of 44.4 ng/mL. This prediction
      was in good agreement with that estimated via the application of the proposed PK
      PD model to the clinical data (i.e., 39.2 ng/mL). These results illustrate the
      utility of the proposed PK-PD model in supporting the quantitative translation of
      preclinical studies into an accurate clinical expectation. As such, the proposed
      PK-PD model is useful for supporting the design, selection, and early development
      of novel KOR antagonists.

PMID- 21847690
TI  - High vascular delivery of EGF, but low receptor binding rate is observed in AsPC
      1 tumors as compared to normal pancreas.
AB  - PURPOSE: Cellular receptor targeted imaging agents present the potential to
      target extracellular molecular expression in cancerous lesions; however, the
      image contrast in vivo does not reflect the magnitude of overexpression expected
      from in vitro data. Here, the in vivo delivery and binding kinetics of epidermal
      growth factor receptor (EGFR) was determined for normal pancreas and AsPC-1
      orthotopic pancreatic tumors known to overexpress EGFR. PROCEDURES: EGFR in
      orthotopic xenograft AsPC-1 tumors was targeted with epidermal growth factor
      (EGF) conjugated with IRDye800CW. The transfer rate constants (k(e), K12, k21,
      k23, and k32) associated with a three-compartment model describing the vascular
      delivery, leakage rate and binding of targeted agents were determined
      experimentally. The plasma excretion rate, k (e), was determined from extracted
      blood plasma samples. K12, k21, and k32 were determined from ex vivo tissue
      washing studies at time points >= 24 h. The measured in vivo uptake of IRDye800CW
      EGF and a non-targeted tracer dye, IRDye700DX-carboxylate, injected
      simultaneously was used to determined k23. RESULTS: The vascular exchange of
      IRDye800CW-EGF in the orthotopic tumor (K12 and k21) was higher than in the AsPC
      1 tumor as compared to normal pancreas, suggesting that more targeted agent can
      be taken up in tumor tissue. However, the cellular associated (binding) rate
      constant (k23) was slightly lower for AsPC-1 pancreatic tumor (4.1 * 10(-4) s(
      1)) than the normal pancreas (5.5 * 10(-4) s(-1)), implying that less binding is
      occurring. CONCLUSIONS: Higher vascular delivery but low cellular association in
      the AsPC-1 tumor compared to the normal pancreas may be indicative of low
      receptor density due to low cellular content. This attribute of the AsPC-1 tumor
      may indicate one contributing cause of the difficulty in treating pancreatic
      tumors with cellular targeted agents.

PMID- 21847691
TI  - DNA content variation in monilophytes and lycophytes: large genomes that are not
      endopolyploid.
AB  - Less than 1% of known monilophytes and lycophytes have a genome size estimate,
      and substantially less is known about the presence and prevalence of
      endopolyploid nuclei in these groups. Thirty-one monilophyte species (including
      three horsetails) and six lycophyte species were collected in Ontario, Canada.
      Using flow cytometry, genome size and degree of endopolyploidy were estimated for
      37 species. Across the five orders covered, 1Cx-values averaged 4.2 pg in the
      Lycopodiales, 18.1 pg for the Equisetales, 5.06 pg for a single representative of
      the Ophioglossales, 14.3 pg for the Osmundales, and 7.06 pg for the Polypodiales.
      There was no indication of endoreduplication in any of the leaf, stem, or root
      tissue analyzed. This information is essential to our understanding of DNA
      content evolution in land plants.

PMID- 21847693
TI  - A perinatal palatable high-fat diet increases food intake and promotes
      hypercholesterolemia in adult rats.
AB  - The main goal of the present study was to evaluate the long-term effects of a
      perinatal palatable high-fat diet on the food intake and cholesterol profile of
      adult rats. Male Wistar rats (aged 22 days) were divided into two groups
      according to their mother's diet during gestation and lactation (C (p), n = 10;
      pups from control mothers; and HL(p) n = 10; pups from mothers fed a palatable
      high-fat diet). At the 76th day, pups were housed individually for 14 days, and
      daily food consumption was determined during a period of 6 days. Blood from 100
      day-old rats was sampled by cardiac puncture. Fasting (12 h) serum glucose, total
      cholesterol, LDL-C, HDL-C, triglycerides (TG), and VLDL-C levels were determined.
      The measurement of food intake was higher in the animals submitted to a
      hyperlipidic diet during the perinatal period. Serum total cholesterol, LDL-C,
      HDL-C, TG, VLDL-C and glycemia were increased in the HL(p) group compared to the
      control group. Our findings show that an early life environment with a high-fat
      diet can contribute to metabolic disease in later life.

PMID- 21847694
TI  - Smart DNA vectors based on cyclodextrin polymers: compaction and endosomal
      release.
AB  - PURPOSE: Neutral beta-cyclodextrin polymers (polybetaCD) associated with cationic
      adamantyl derivatives (Ada) can be used to deliver plasmid DNA into cells. In
      absence of an endosomolytic agent, transfection efficiency remains low because
      most complexes are trapped in the endosomal compartment. We asked whether
      addition of an imidazole-modified Ada can increase efficiency of
      polybetaCD/cationic Ada-based delivery system. METHODS: We synthesized two
      adamantyl derivatives: Ada5, which has a spacer arm between the Ada moiety and a
      bi-cationic polar head group, and Ada6, which presents an imidazole group.
      Strength of association between polybetaCD and Ada derivatives was evaluated by
      fluorimetric titration. RESULTS: Gel mobility shift assay, zeta potential, and
      dark field transmission electron microscopy experiments demonstrated the system
      allowed for efficient DNA compaction. In vitro transfection experiments performed
      on HepG2 and HEK293 cells revealed the quaternary system polybetaCD/Ada5/Ada6/DNA
      has efficiency comparable to cationic lipid DOTAP. CONCLUSION: We successfully
      designed fine-tuned DNA vectors based on cyclodextrin polymers combined with two
      new adamantyl derivatives, leading to significant transfection associated with
      low toxicity.

PMID- 21847696
TI  - Lymph node ratio should be considered for incorporation into staging for breast
      cancer.
AB  - BACKGROUND: We sought to determine whether lymph node ratio (LNR; defined as
      number of positive nodes/number of nodes dissected) provides additional
      prognostic information in node-positive breast cancer patients. METHODS: Data
      from a cohort of 319 node-positive breast cancer patients diagnosed between 1956
      and 1982 were analyzed for overall survival (OS) on the basis of current American
      Joint Committee on Cancer (AJCC) nodal staging versus LNR. RESULTS: In terms of
      AJCC categorization, 157 patients (49.2%) were pN1 (1-3 positive nodes), 97
      (30.4%) were pN2 (4-9 positive nodes), and 65 (20.4%) were pN3 (>=10 positive
      nodes). In terms of LNR, 90 (28.2%) were low risk (LNR = 0.01-0.20), 119 (38.3%)
      were intermediate risk (LNR = 0.21-0.65), and 110 (34.5%) were high risk (LNR >
      0.65). The median follow-up was 68.7 months. AJCC nodal status correlated with OS
      (median OS 85.9, 70.4, and 48.4 months for pN1-3, respectively, P = 0.018). LNR
      also correlated with OS (median OS 105.8, 72.2, and 48.4 months for the low-,
      intermediate-, and high-risk groups, respectively, P < 0.005). On multivariate
      analysis, LNR predicted OS independent of pN status (P < 0.001). Stratifying by
      pN status, LNR could discriminate distinct subpopulations of patients with
      significantly different OS rates. In a multivariate model controlling for
      clinicopathologic factors (tumor size, grade, estrogen receptor, progesterone
      receptor, and her-2-neu status), LNR remained a significant predictor of OS (P <
      0.001). CONCLUSIONS: LNR has the ability to discriminate populations with
      different OS rates within traditional AJCC node classification groups and
      predicts OS independent of traditional clinicopathologic factors. These results
      should be validated and considered for future incorporation into the breast
      cancer staging system.

PMID- 21847695
TI  - Transgastric endoscopic pneumoperitoneum versus laparoscopy: effects on host
      systemic and peritoneal inflammatory responses in a porcine model.
AB  - BACKGROUND: The host systemic and peritoneal immune responses during natural
      orifice transluminal endoscopic surgery (NOTES) continues to be delineated. The
      immune response to laparoscopy (LAP) has been favorably depicted. However, the
      immunologic effects of NOTES are yet to be determined, and the introduction of
      contaminants via the host orificium may have deleterious effects. The purpose of
      this study was to characterize the effect that NOTES would have on porcine
      systemic and peritoneal immune function. METHODS: Twenty-four pigs were divided
      into three groups: ENDO (upper-endoscopy control), NOTES, and LAP. All animals
      had blood and peritoneal lavage samples collected for cytokine analysis pre- and
      postoperatively. Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin
      10 (IL-10), tumor necrosis factor alpha (TNFalpha), and interferon gamma
      (IFNgamma) levels were quantified using enzyme-linked immunosorbent assay
      (ELISA). Peritoneal lavage samples were cultured and identified by group and time
      of collection for microbiological analysis. RESULTS: TNFalpha was found in
      detectable levels in serum samples of all three groups. For the NOTES group,
      there was a significant increase in TNFalpha at t = 1 h (P < 0.01), which dropped
      significantly at t = 48 h (P < 0.01). IL-1beta was present as an early response
      in NOTES lavage samples (t = 0 and t = 1 h). Both LAP and NOTES had similar
      elevation of IL-1beta in the final lavage samples at t = 48 h. The other
      cytokines were not consistently found above detectable levels in any group.
      Similar microbiological contaminants were found in the ENDO and LAP groups. In
      the NOTES group, no significant growth was observed from cultures at 48 h.
      CONCLUSIONS: For measurable cytokines, the NOTES inflammatory response was not
      significantly different from that of the LAP group. NOTES did not carry a
      significantly increased amount of microbiological contamination at 48 h compared
      to LAP. These data suggest that the host immune response to NOTES does not
      significantly differ from that to LAP in a porcine model.

PMID- 21847697
TI  - Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the
      Memorial Sloan-Kettering Cancer Center experience.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) has been gathering increased
      recognition as an alternative to more traditional mastectomy approaches.
      Initially, questions concerning its oncologic safety limited the use of NSM.
      Nevertheless, mounting evidence supporting the practice of NSM for both
      prophylactic and oncologic purposes is leading to its more widespread use and
      broadened indications. METHODS: Using a prospectively maintained database, we
      reviewed our experience of 353 NSM procedures performed in 200 patients over the
      past 10 years. RESULTS: The indications for surgery were: 196 prophylactic risk
      reduction (55.5%), 74 ductal carcinoma in situ (DCIS) (20.8%), 82 invasive cancer
      (23.2%), and 1 phyllodes tumor (0.5%). The nipple areolar complex (NAC) was
      entirely preserved in 341 mastectomies (96.7%). There were 11 patients (3.1%) who
      were found to have cancer at the nipple margin, warranting further excision. A
      total of 69 breasts (19.5%) had some degree of skin desquamation or necrosis, but
      only 12 (3.3%) required operative debridement, of which 3 breasts (1%)
      necessitated removal of a breast implant. Also, 6 patients (2%) were treated for
      infection. Of the 196 prophylactic NSMs, 11 specimens (5.6%) were found to harbor
      occult cancer (8 DCIS and 3 invasive cancers). One patient who underwent NSM for
      invasive ductal carcinoma in 2006 developed metastatic disease to her brain. No
      other recurrences are attributable to the 353 NSMs. CONCLUSIONS: The trends
      demonstrate the increasing acceptance of NSM as a prophylactic procedure as well
      as for therapeutic purposes. Although NSM is not standard, our experience
      supports the selective use of NSM in both prophylactic and malignant settings.

PMID- 21847698
TI  - Introduction of Eric Whitacre, MD, president 2010-2011: American Society of
      Breast Surgeons annual meeting 2011.

PMID- 21847699
TI  - Correlation of ductal lavage cytology with ductoscopy-directed duct excision
      histology in women at high risk for developing breast cancer: a prospective,
      single-institution trial.
AB  - OBJECTIVES: The study was designed to determine which histological lesions
      produce cellular atypia in lavage specimens and whether ductoscopy adds useful
      information for the evaluation of high-risk patients with atypical lavage
      cytology. METHODS: We prospectively recruited women >=35 years at high risk for
      developing breast cancer. All underwent ductal lavage. Women found to have atypia
      underwent ductoscopy-directed duct excision (group 1). Women without atypia were
      observed (group 2). Data included patient demographics, risk assessment,
      cytologic and histologic findings, and outcomes. Descriptive statistics were
      utilized for data summary and were compared using Fisher's exact test. RESULTS:
      We enrolled 102 women; 93 (91%) were Caucasian. Their median age was 49 (range 34
      73) years with a median follow-up of 80 (range 5-90) months. Overall, 27 (26%)
      had atypical lavage cytology (group 1), and 75 (74%) had benign cytology (group
      2). Subsequent duct excision in group 1 revealed benign histology in 11 (44%),
      papillomas in 9 (36%), atypical hyperplasia (AH) in 4 (16%), and ductal carcinoma
      in situ (DCIS) in 1 (4%). At follow-up, three patients developed breast cancer,
      including one group 1 patient and two group 2 patients. There were no differences
      between groups 1 and 2 according to patient demographics, Gail scores, or risk
      for subsequent breast cancer (P > 0.05). CONCLUSIONS: Although 20% of high-risk
      women with ductal lavage atypia have AH or malignancy on subsequent excision, the
      majority do not. Atypia identified by ductal lavage is not associated with a
      higher risk of developing subsequent breast cancer, even in this high-risk
      population.

PMID- 21847701
TI  - Genetic and environmental factors influencing BMI development from adolescence to
      young adulthood.
AB  - BMI increases progressively from adolescence to young adulthood. The aims of the
      present study were firstly, to investigate the extent to which genetic and
      environmental influences account for differences in BMI trajectories during this
      period, and secondly to examine whether boys and girls show divergences in these
      influences, as their BMI normally start differing across adolescence. The study
      sample consisted of 4,915 monozygotic and like- and unlike-sex dizygotic twins,
      born between 1975 and 1979. Data on BMI was gathered when twins were on average
      16.1, 17.1, 18.6 and 24.4 years old. Genetic and environmental influences on the
      BMI trajectories were modeled using a latent growth curve approach. The results
      showed that the heritability of BMI decreased slightly after the adolescence
      period, from ~ 80 to 70%. BMI transition from adolescence to young adulthood was
      best described by a quadratic trajectory that was highly accounted (61.7-86.5%)
      for by additive genetic influences. Genetic influences on BMI level showed a low
      correlation with those on the trend in BMI with age indicating that different
      sets of genes underlie the change of BMI during this period. Importantly, the
      analyses also evidenced that different genetic and environmental influences may
      underlie boys and girls evolution. In conclusion, our results suggested specific
      genetic influences accounting for the BMI rate-of-change from adolescence to
      young adulthood. This indicates that the specific genes behind BMI level may not
      be the same as the genes affecting BMI change which should be taken into account
      in further efforts to identify these genes.

PMID- 21847700
TI  - Breast cancer in Hong Kong, Southern China: the first population-based analysis
      of epidemiological characteristics, stage-specific, cancer-specific, and disease
      free survival in breast cancer patients: 1997-2001.
AB  - BACKGROUND: Cancer registries have been set up worldwide to provide information
      for cancer health planning. There are known variations in breast cancer incidence
      and mortality worldwide. However, breast cancer incidence, pathological
      characteristics, and survival data is still under-reported in Asian countries.
      This is the first comprehensive population-based breast cancer study performed
      using population database of the Hong Kong Cancer Registry. METHODS: A
      retrospective review of medical records of 8,961 subjects who were diagnosed with
      breast cancer between January 1, 1997 to December 31, 2001 and followed up to
      December 31, 2007. Descriptive statistics were employed to analyze the
      epidemiological and clinical data. Estimates of overall, disease-free, and cancer
      specific survival at 5 years were estimated by the Kaplan-Meier method and stage
      specific relative survival rates were calculated. RESULTS: A total of 7,630
      breast cancer patients' medical records and dataset were available during this
      period, and 7,449 subjects were eligible for the final analysis. Median follow-up
      was 84 months. A total of 47.4% were diagnosed with breast cancer at age 49 years
      and younger; 22.2%, 46.9%, 10.8%, and 4.1% presented at stages I, II, III, and
      IV, respectively. A total of 53.5% had ER-positive cancer, and 20.3% had HER2
      positive cancers; 13.4% had triple-negative cancers. The relative, cancer
      specific, and disease-free survival rates at 5 years were 84%, 85.2%, and 81.2%,
      respectively. DISCUSSION: We performed the first comprehensive population-based
      breast cancer epidemiology study in Southern China using the Hong Kong Cancer
      Registry database. This provides a baseline study cohort for comparative studies
      with other Asian countries and Chinese who have migrated to the West.

PMID- 21847702
TI  - Impact of a neurointensivist on outcomes in critically ill stroke patients.
AB  - BACKGROUND: Current guidelines for management of critically ill stroke patients
      suggest that treatment in a neurocritical care unit (NCCU) and/or by a
      neurointensivist (NI) may be beneficial, but the contribution of each to outcome
      is unknown. The relative impact of a NCCU versus NI on short- and long-term
      outcomes in patients with acute ischemic stroke (AIS), intracerebral hemorrhage
      (ICH), and aneurysmal subarachnoid hemorrhage (SAH) was assessed. METHODS: 2,096
      stroke patients admitted to a NCCU or nonneuro ICU at a tertiary stroke center
      were analyzed before the appointment of a NI, during the NI's tenure, and after
      the NI departed and was not replaced. Data included admission ICU type,
      availability of a NI, age, NIHSS, ICH score, and 3 and 12 month outcome. RESULTS:
      For AIS, compared to the time interval with a NI, departure of the NI predicted a
      worse rate of return to pre-stroke function at 3 months. For ICH, NCCU treatment
      predicted shorter ICU and hospital LOS but had no effect on short- or long-term
      outcomes. No effect of a NI was seen. For SAH, availability of an NI (but not an
      NCCU) predicted improved outcomes but longer ICU LOS. Disposition and in-hospital
      mortality improved when a NI was present, but continued improvement did not occur
      after the NI's departure. CONCLUSION: Presence of an NI was associated with
      improved clinical outcomes. This effect was more evident in patients with SAH.
      Patients with ICH tend to have poor outcomes regardless of the presence of a NCCU
      or a NI.

PMID- 21847703
TI  - Rituximab as a new therapeutic option in granulomatosis with polyangiitis: a
      report of two cases.
AB  - Findings of several reports suggest that rituximab, a chimeric monoclonal anti
      CD20 antibody causing B-lymphocyte depletion, might represent a treatment option
      for people with granulomatosis with polyangiitis (GPA) (former Wegener's
      granulomatosis). This study presents the results of rituximab treatment in two
      patients with treatment-refractory GPA. First patient received rituximab for a
      granulomatous posterior orbital mass lesion, and eye symptoms were resolved after
      three courses of treatment. The second patient had eye and paranasal sinus
      involvement and benefited from two courses of rituximab treatment, with
      significant clinical improvement. Rituximab may represent an effective novel
      treatment for remission induction in GPA.

PMID- 21847704
TI  - Acute kidney injury during aortic arch surgery under deep hypothermic circulatory
      arrest.
AB  - PURPOSE: The aim of this investigation was to describe the renal outcome and to
      identify risk factors for acute kidney injury (AKI), as defined by the Acute
      Kidney Injury Network (AKIN), during aortic arch surgery (AAS) under deep
      hypothermic circulatory arrest (DHCA). METHODS: A retrospective and observational
      study has been performed. One hundred thirty-five patients requiring AAS under
      DHCA were studied. RESULTS: Seventy-one patients (52.6%) developed AKI during the
      postoperative period. A logistic regression analysis identified three independent
      risk factors for AKI: preoperative hypertension (HT), emergency surgery, and
      duration of DHCA. Renal replacement therapy (RRT) was required in four patients
      (3.0%). The postoperative mortality rate among the patients with AKI was 2.8%,
      which was not statistically different from the rate of 1.6% observed in the non
      AKI group (P = 0.62). CONCLUSIONS: A high incidence of AKI during AAS under DHCA
      was confirmed. Because AKI is highly associated with aortic surgery, novel
      approaches for protecting the kidneys other than deep hypothermia are needed. The
      logistic regression model identified HT, emergency surgery, and duration of DHCA
      as independent risk factors for AKI.

PMID- 21847705
TI  - Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: open
      label pilot study for assessing the efficacy, tolerability and impact on quality
      of life.
AB  - We conducted a prospective, observational study to verify the efficacy,
      tolerability and impact on quality of life, mood and global neurocognitive
      performances of oxcarbazepine monotherapy in patients with brain tumor-related
      epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients
      (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and
      7 in monotherapy with other antiepileptics) and introduced oxcarbazepine
      monotherapy because of uncontrolled seizures and/or side effects. At first visit,
      patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung
      self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary
      was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5
      patients died and 10 dropped out). Totals of 16 patients underwent both
      chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4
      did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230
      mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant
      difference in seizure freedom rate (P = 0.002) between baseline and final follow
      up in the intent-to-treat population. Six patients (24%) had serious side effects
      and one patient (4%) mild. Logistic regression revealed that, in our study,
      chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure
      outcome (P = 0.658). The test evaluation at final follow-up showed a significant
      improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to
      be efficacious in controlling seizures and in improving mood in patients with
      BTRE, but special caution should be taken when it is administered during
      radiotherapy.

PMID- 21847706
TI  - Imaging 18F-fluorodeoxy glucose/11C-methionine uptake decoupling for
      identification of tumor cell infiltration in peritumoral brain edema.
AB  - Discriminating tumor infiltrative and vasogenic brain edema in malignant gliomas
      is important although challenging in clinical settings. This study challenged
      this issue by performing voxel-wise analysis of (18)F-fluorodeoxy glucose (FDG)
      and (11)C-methionine positron emission tomography (PET) in peritumoral brain
      edemas. The authors studied ten malignant glioma and nine meningioma patients
      with peritumoral brain edema. A voxel-wise analysis of FDG and (11)C-methionine
      PET was performed in order to quantify the correlation between uptake of these
      tracers in normal brain tissue and peritumoral brain edema. Decoupling score of
      the uptake of two tracers was calculated as the z-score from the estimated
      correlation between uptake of the two tracers in normal brain tissue. The
      decoupling score was also converted into images for visual inspection. Average
      decoupling score in the peritumoral brain edema was calculated and compared
      between those obtained from malignant gliomas and meningiomas. FDG and (11)C
      methionine uptake showed a reproducible linear correlation in normal brain
      tissue. This correlation was preserved in peritumoral edema of meningioma, but
      not in that of malignant gliomas. In malignant gliomas, higher (11)C-methionine
      uptake compared to that estimated by the FDG uptake in normal brain tissue was
      observed, thus suggesting that decoupling was caused by tumor infiltration.
      Visual inspection of the decoupling score enabled discrimination of tumor
      infiltrative and vasogenic edema. The average decoupling scores of the
      peritumoral brain edema in malignant gliomas were significantly higher than those
      in meningiomas (2.9 vs. 0.7, P = 0.0003). As a conclusion, FDG/(11)C-methionine
      uptake decoupling score can be used for the discrimination of tumor infiltrative
      and vasogenic brain edema. The proposed method also suggests the possibility of
      accurately detecting tumor infiltration into brain tissues in gliomas, providing
      significant information for treatment planning and follow-up.

PMID- 21847709
TI  - Efficacy of lower-extremity venous thrombolysis in the setting of congenital
      absence or atresia of the inferior vena cava.
AB  - PURPOSE: A rare but described risk factor for deep venous thrombosis (DVT),
      predominantly in the young, is congenital agenesis or atresia of the inferior
      vena cava (IVC). The optimal management for DVT in this subset of patients is
      unknown. We evaluated the efficacy of pharmacomechanical catheter-directed
      thrombolysis (PCDT) followed by systemic anticoagulation in the treatment of
      acute lower-extremity DVT in the setting of congenital IVC agenesis or atresia.
      MATERIALS AND METHODS: Between November of 2005 and May of 2010, six patients
      (three women [average age 21 years]) were referred to our department with acute
      lower-extremity DVT and subsequently found to have IVC agenesis or atresia on
      magnetic resonance imaging. A standardized technique for PCDT (the Angiojet
      Rheolytic Thrombectomy System followed by the EKOS Microsonic Accelerated
      Thrombolysis System) was used for all subjects. Successful thrombolysis was
      followed by systemic heparinization with transition to Coumadin or low molecular
      weight heparin and compression stockings. Subjects were followed-up at 1, 3, and
      then every 6 months after the procedure with clinical assessment and bilateral
      lower-extremity venous ultrasound. RESULTS: All PCDT procedures were technically
      successful. No venous stenting or angioplasty was performed. The average
      thrombolysis time was 28.6 h (range 12-72). Two patients experienced heparin
      induced thrombocytopenia, and one patient developed a self-limited knee
      hemarthrosis, No patients were lost to follow-up. The average length of follow-up
      was 25.8 +/- 20.2 months (range 3.8-54.8). No incidence of recurrent DVT was
      identified. There were no manifestations of postthrombotic syndrome. CONCLUSIONS:
      PCDT followed by systemic anticoagulation and the use of compression stockings
      appears to be safe and effective in relatively long-term follow-up treatment of
      patients who present with acute DVT and IVC agenesis or atresia.

PMID- 21847708
TI  - Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases
      using yttrium-90 microspheres.
AB  - PURPOSE: To evaluate safety, efficacy, and symptom-control of radioembolization
      in patients with unresectable liver metastases from neuroendocrine tumors
      (NETLMs). MATERIALS AND METHODS: Forty-two patients (mean age of 62 years) with
      treatment-refractory NETLMs underwent radioembolization using yttrium-90 ((90)Y)
      resin microspheres. Posttreatment tumor response was assessed by cross-sectional
      imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor
      marker levels. Laboratory and clinical toxicities and clinical symptoms were
      monitored. RESULTS: The median activity delivered was 1.63 GBq (range 0.63-2.36).
      Imaging follow-up using RECIST at 3-month follow-up demonstrated partial
      response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of
      patients, respectively. In 97.5% of patients, the liver lesions appeared
      hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40
      patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3
      months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were
      no acute or delayed toxicities greater than grade 2 according to Common
      Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced
      liver disease was noted. Improvement of clinical symptoms 3 months after
      treatment was observed in 36 of 38 symptomatic patients. CONCLUSION:
      Radioembolization with (90)Y-microspheres is a safe and effective treatment
      option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect
      is supported by good local tumor control, decreased tumor-marker levels, and
      improved clinical symptoms. Further investigation is warranted to define the role
      of radioembolization in the treatment paradigm for NETLMs.

PMID- 21847707
TI  - The nonsteroidal anti-inflammatory drug celecoxib suppresses the growth and
      induces apoptosis of human glioblastoma cells via the NF-kappaB pathway.
AB  - Gliomas are devastating primary tumors of the central nervous system and tend to
      recur even after standard therapy. Celecoxib, the selective COX-2 nonsteroidal
      anti-inflammatory drug, has anti-neoplastic activity against several
      malignancies. Accumulating evidence suggests that several COX-2-independent
      mechanisms may also be involved in the anti-tumor effects of celecoxib.
      Deregulation of the NF-kappaB signaling pathway contributes to enhanced glioma
      cell survival, proliferation, and chemoresistance. In this study, we examined the
      efficacy of celecoxib in suppressing the growth of glioblastoma cell lines. We
      observed that treatment with celecoxib significantly reduced the proliferation of
      a variety of GBM cell lines in a dose-dependent manner and also induced
      apoptosis, which was evident from enhanced caspase-3 and 8 activity, PARP
      cleavage, and TUNEL positive cells. Celecoxib treatment significantly down
      regulated TNF-alpha induced NF-kappaB nuclear translocation, NF-kappaB DNA
      binding activity, and NF-kappaB-dependent reporter gene expression in U373 and
      T98G cells in a dose-dependent manner. Furthermore, celecoxib suppressed
      IkappaBalpha degradation and phosphorylation and reduced IKK activity in a dose
      dependent manner. This study provides evidence that celecoxib suppresses the
      growth of GBM cell lines partly by inhibiting the NF-kappaB signaling pathway.

PMID- 21847710
TI  - Syncopal migraine.
AB  - OBJECTIVE: A subgroup of syncope patients report migraine headaches immediately
      preceding or following syncope, and some respond to anti-migrainous prophylactic
      agents. This study aimed to describe the frequency of migrainous features
      concurrent with episodes of syncope and to propose clinical criteria for
      assessing whether a migrainous mechanism might underlie syncope. METHODS: This
      retrospective, questionnaire-based study developed criteria for syncopal migraine
      based on the International Classification of Headache Disorders II (ICHD-II)
      migraine criteria. Two hundred and forty-eight recurrent syncope subjects (>3
      episodes) were stratified based on the presence (N = 127) or absence (N = 121) of
      a headache concurrent with syncopal episodes. Syncopal headaches were classified
      as either syncopal migraine (meeting ICHD-II criteria for migraine or probable
      migraine, without aura) or nonspecific (not meeting the criteria for syncopal
      migraine). The syncope groups were then compared to 199 subjects with migraine
      headaches using chi-square and Cochran-Armitage test for trend. RESULTS: Nearly
      one-third of recurrent syncope subjects met criteria for syncopal migraine. This
      group resembled the migraine headache population more than the syncope population
      in age, gender, autonomic testing, and comorbid conditions. The syncopal migraine
      group also reported a longer duration of syncope and a longer recovery time to
      normal. Finally, anti-migrainous medications reduced syncope in half of the
      syncopal migraine subjects. INTERPRETATION: Syncope may have a migrainous basis
      more commonly than previously suspected, and we suggested criteria to identify
      these patients. Syncopal migraine appears epidemiologically more closely related
      to migraine than to reflex syncope.

PMID- 21847711
TI  - Improving satisfaction in patients receiving mental health care: a case study.
AB  - Patient satisfaction is increasingly becoming an important component of quality
      for behavioral health care systems. The following report describes Group Health
      Cooperative's Behavioral Health Services department experiences over a 5-year
      period in moving from uncertainty about the value of patient satisfaction and the
      ability to positively impact patient ratings to achieving a significant
      improvement in patient ratings of satisfaction with mental health care. In this
      process, the Behavioral Health Department developed a deeper understanding of
      patient requirements and improvement strategies which could impact these
      requirements. A description of the results achieved along with the role of
      quality improvement processes in understanding and improving patient satisfaction
      in mental health care is presented.

PMID- 21847712
TI  - Residential racial composition, spatial access to care, and breast cancer
      mortality among women in Georgia.
AB  - We explored the association between neighborhood residential racial composition
      and breast cancer mortality among Black and White breast cancer patients in
      Georgia and whether spatial access to cancer care mediates this association.
      Participants included 15,256 women living in 15 metropolitan statistical areas in
      Georgia who were diagnosed with breast cancer between 1999 and 2003. Residential
      racial composition was operationalized as the percent of Black residents in the
      census tract. We used gravity-based modeling methods to ascertain spatial access
      to oncology care. Multilevel Cox proportional hazards models and mediation
      analyses were used to test associations. Black women were 1.5 times more likely
      to die from breast cancer than White women. Residential racial composition had a
      small but significant association with breast cancer mortality (hazard ratios
      [HRs] = 1.04-1.08 per 10% increase in the percent of Black tract residents).
      Individual race did not moderate this relationship, and spatial access to care
      did not mediate it. Residential racial composition may be part of the
      socioenvironmental milieu that produces increased breast cancer mortality among
      Black women. However, there is a lack of evidence that spatial access to oncology
      care mediates these processes.

PMID- 21847713
TI  - Effect of ruminally protected methionine on body weight gain and growth of
      antlers in red deer (Cervus elaphus) in the humid tropics.
AB  - Sixteen male red deer (Cervus elaphus), with an initial weight of 93.83 +/- 4.38
      kg were used to study the effect of the dietary level of ruminally protected
      methionine (RPM) on growth, antler morphometry and serum metabolites. The deer
      were allowed to graze and were individually supplemented with concentrate to
      provide 0, 2.5, 3.5 or 4.5 g/day of RPM for 65 days. There was a quadratic effect
      on daily weight gain (0.163, 0.098, 0.147 and 0.172 kg/day; P < 0.005) and antler
      beam length (59.7, 63.6, 63.0 and 57.2 cm; P < 0.02) for RPM levels of 0 to 4.5
      g/day, respectively. The brow tine length and the number of points were similar
      across all treatments. Serum glutamic pyruvate transaminase (SGPT) was reduced
      (quadratic effect; P < 0.02; 22.0, 29.6, 18.0 and 17.8 IU/l) to RPM levels of 0
      to 4.5 g/day, respectively, whereas other metabolites (glucose, cholesterol,
      urea, creatinine, total protein and serum glutamic oxaloacetic transaminase
      [SGOT]) were unchanged. Increasing the RPM dose did not affect weight gain or
      antler growth. Methionine supplementation reduced the activity of SGPT.

PMID- 21847714
TI  - Nerve transfers using collateral branches of the brachial plexus as donors in
      patients with upper palsy--thirty years' experience.
AB  - BACKGROUND: Nerve transfers in cases of directly irreparable or high-level
      extensive brachial plexus traction injuries have been done using a variety of
      donor nerves with various success, but an ideal method has not been established.
      The purpose of this study is to analyze the results of nerve transfers using the
      thoracodorsal and medial pectoral nerves as donors in patients with upper palsy.
      METHODS: This retrospective study included 40 patients with 29 procedures using
      the thoracodorsal nerve and 33 procedures using the medial pectoral nerve as
      donors for reinnervation of the musculocutaneous or axillary nerve. Both nerves
      were used simultaneously in 22 of these patients. The thoracodorsal nerve was
      transferred in 13 patients to the musculocutaneous nerve and in nine patients to
      the axillary nerve. The medial pectoral nerve was transferred in nine patients to
      the musculocutaneous nerve and in 13 patients to the axillary nerve. The results
      were analyzed according to the donor nerve, the age of the patient, and the
      timing of surgery. RESULTS: The total rate of recovery for elbow flexion was
      94.1%, for shoulder abduction 89.3%, and for shoulder external rotation 64.3%.
      The corresponding rates of recovery using the thoracodorsal nerve were 100, 93.7,
      and 68.7%, respectively. The rates of recovery with medial pectoral nerve
      transfers were 90.5, 83.3, and 58.3%, respectively. Despite the obvious
      differences in the rates of recovery, statistical significance was found only
      between the rates and quality of recovery for the musculocutaneous and axillary
      nerve using the thoracodorsal nerve as donor. CONCLUSIONS: According to our
      findings, nerve transfers using collateral branches of the brachial plexus in
      cases with upper palsy offer several advantages and yield high rate and good
      quality of recovery.

PMID- 21847715
TI  - The IDF Statement: a big and long-awaited step for our diabetic patients.

PMID- 21847721
TI  - ALARA (as low as reasonably achievable) CT 2011--executive summary.

PMID- 21847722
TI  - Where we were, what has changed, what needs doing: a decade of progress.
AB  - In the last decade, there has been recognition of the effects of low-dose
      radiation in children. A critical mass of scientists, health care providers and
      manufacturers of radiation-producing imaging equipment has come together to
      educate ordering physicians to request only indicated examinations and
      radiologists to achieve low-dose examinations with diagnostic images. The forces
      that caused these changes will be discussed.

PMID- 21847723
TI  - Image Gently: progress and challenges in CT education and advocacy.
AB  - Significant progress has been made in radiation protection for children during
      the last 10 years. This includes increased awareness of the need for radiation
      protection for pediatric patients with international partnerships through the
      Alliance for Radiation Safety in Pediatric Imaging. This paper identifies five
      areas of significant progress in radiation safety for children: the growth of the
      Alliance; the development of an adult radiation protection campaign Image
      WiselyTM; increased collaboration with government agencies, societies and the
      vendor community; the development of national guidelines in pediatric nuclear
      medicine, and the development of a size-based patient dose correction factor by
      the American Association of Physicists in Medicine, Task Group 204. However, many
      challenges remain. These include the need for continued education and change of
      practice at adult-focused hospitals where many pediatric CT exams are performed;
      the need for increased emphasis on appropriateness of pediatric imaging and
      outcomes research to validate the performance of CT studies, and the advancement
      of the work of the first pediatric national dose registry to determine the "state
      of the practice" with the final goal of establishing ranges of optimal CT
      technique for specific scan indications when imaging children with CT.

PMID- 21847724
TI  - Justification and optimization of CT in children: how are we performing?
AB  - It has been 10 years since the original pediatric CT ALARA conference in 2001, so
      it is fitting that we look back at our progress. The following material will look
      at how we might quantify our performance regarding the justification and
      optimization of radiation protection. It will also summarize some of the efforts
      and initiatives that have likely contributed to these changes.

PMID- 21847725
TI  - Estimated pediatric radiation dose during CT.
AB  - State-of-the-art CT scanners typically display two dose indices: CT dose index
      (CTDI(vol) [mGy]) and dose length product (DLP [mGy-cm]) based on one of two
      standard CTDI phantoms (16- or 32-cm diameter) used in the calculation of
      CTDI(vol). CTDI(vol) represents the radiation produced by the CT scanner, not the
      radiation dose to an individual patient. Pediatric radiologists, aware of this
      discrepancy, have requested a method to estimate the CT patient dose based on the
      size of the pediatric patient or small adult. This paper describes the method
      developed by AAPM Task Group 204 to provide a better estimate of CT patient dose.
      These improved estimates of patient dose provide radiologists with a practical
      tool to better manage the radiation dose their patients receive. In the future,
      size-specific dose estimates (SSDE) received by the patient should be included in
      the patient's electronic medical record to help radiologists better assess risk
      versus benefit for their patients.

PMID- 21847726
TI  - CT dose and risk estimates in children.
AB  - Pediatric CT radiation dose and risk assessment are important but challenging,
      especially given inherent uncertainties. It is still necessary for those involved
      in medical imaging of children to have an understanding of the extent of existing
      knowledge for dose assessment and risk, as well as ongoing work at improvements.

PMID- 21847727
TI  - CT dose reduction in practice.
AB  - Greater than 10% of diagnostic imaging studies performed in developed countries
      are CT examinations. In the United States, as many as 60 million CT studies are
      performed each year, up to 7 million of which are performed in pediatric
      patients. In the spirit of the ALARA principle, both adult and pediatric
      radiologists should strive to decrease pediatric radiation exposure whenever
      possible. This can be achieved by utilizing imaging studies that do not require
      the use of ionizing radiation, thus decreasing the number of CT studies
      performed. If a CT study is indicated, the delivered dose should be optimized to
      use the lowest possible dose level while still answering the clinical question.

PMID- 21847728
TI  - Advances in CT technology and application to pediatric imaging.
AB  - The use of imaging in both hospital and non-hospital settings has expanded to
      more than 70 million CT procedures in the United States per year, with nearly 10%
      of procedures performed on children. The availability of multiple-row detector CT
      (MDCT) systems has played a large part in the wider usage of CT. This rapid
      increase in CT utilization combined with an increasing concern with regard to
      radiation exposure and associated risk demands the need for optimization of MDCT
      protocols. This manuscript will briefly discuss how technology has changed in
      regard to MDCT protocols, helping to reduce radiation dose in CT, especially in
      pediatric imaging.

PMID- 21847729
TI  - The appropriate use of CT: quality improvement and clinical decision-making in
      pediatric emergency medicine.
AB  - An increasing number of patients presenting to a shrinking number of hospital
      emergency departments has contributed to challenges to providing high-quality
      care, specifically care that is safe, efficient and effective. These challenges
      are magnified by trends in CT utilization with uncertain implications for care
      delivery. The utility of CT poses challenges to the pediatric emergency medicine
      physician to balance risk with potential benefit. We describe the process of
      evidence-based clinical decision-making to define the appropriate use of CT
      studies. Strategies for minimizing CT utilization in managing appendicitis,
      traumatic brain injury and cervical spine injuries are described. Clinical
      scores, clinical decision rules and evidence-based guidelines can assist the
      clinician in providing high-quality care through effective utilization of CT.

PMID- 21847730
TI  - Oncological imaging: tumor surveillance in children.
AB  - As the need for accurate diagnostic imaging often continues throughout a cancer
      survivor's life, imaging methods with the least toxicity must be used so as to
      provide needed information without contributing to long-term sequelae that might
      compound toxicities inherent with the primary disease and its treatment. In this
      regard, the costs, benefits and potential risks of post-therapy monitoring for
      disease recurrence warrant periodic review. Unfortunately, few analyses are
      available regarding the impact of surveillance imaging on the detection of
      disease recurrence, salvage rates of relapse disease and long-term survival
      outcomes for pediatric cancer survivors. This review will examine the role and
      limitations of surveillance imaging in pediatric oncology.

PMID- 21847732
TI  - Sedation and anesthesia issues in pediatric imaging.
AB  - Sedation and anesthesia for pediatric imaging departments has changed
      dramatically for the following reasons: (1) radiologists have stopped sedating
      patients; (2) the majority of sedations are not for CT (because of the speed of
      the procedure) but for MR, which lasts 45 min or greater; (3) a cadre of services
      -pediatricians, emergency medicine physicians, hospitalists and intensivists, as
      well as anesthesiologists--can provide the services. These changes have
      significantly influenced the type of agents utilized for sedation and anesthesia
      and, most important, have created operational issues for MR departments.
      Nevertheless, it is important for each imaging department to create a uniform
      approach to sedation, taking into account patient expectations, efficiency of
      through-put, facilities and personnel available, and institutional costs.

PMID- 21847731
TI  - PET-CT in children: where is it appropriate?
AB  - The use of PET/PET-CT is a rapidly growing area of imaging and research in the
      care of children. Until recently, diagnostic imaging methods have provided either
      anatomical or functional assessment. The development of fused imaging modalities,
      such as PET-CT or PET-MRI, now provides the opportunity for simultaneously
      providing both anatomical and functional or physiological assessment. This review
      will discuss current established uses of PET-CT, possible uses and potential
      research investigations in the use of this modality in the pediatric population.
      The focus of this paper will be its use in children being treated for non-central
      nervous system and non-cardiac disorders.

PMID- 21847734
TI  - Pediatric CT--the challenge of dose records.
AB  - With an increasing professional and public awareness of the future risk
      associated with ionizing radiation in medical imaging has come a growing
      discussion of the need for improved dose records. The increased radio-sensitivity
      of children and the greater number of years in their future makes this of
      particular relevance in pediatric practice. Personal dose logs, institutional
      records and national dose registries or databases should all play a part in
      efforts to improve dose records. We present points for discussion and a few
      initial projects to demonstrate the potential benefits and challenges of creating
      dose records. The emphasis of this manuscript is on CT dose records.

PMID- 21847733
TI  - Sedation and anesthesia for CT: emerging issues for providing high-quality care.
AB  - During the past decades, the use of CT to diagnose conditions and monitor
      treatment in the pediatric setting has increased. Infants and children often
      require procedural sedation to maintain a motionless state to ensure high-quality
      imaging. Various medication regimens have been recommended to achieve
      satisfactory sedation for this painless procedure. While the incidence of adverse
      events remains low, procedural sedation carries the risk of serious morbidity and
      mortality. The use of evidence-based, structured approaches to procedural
      sedation should be used to reduce variation in clinical practice and improve
      outcomes.

PMID- 21847735
TI  - Point/counterpoint: dose-related issues in cardiac CT imaging.
AB  - This manuscript reviews some of the more controversial dose-related issues in
      cardiac CT imaging. Discussion covers the relative merits of cardiac CT versus
      MR, advantages and concerns regarding gated versus nongated cardiac CT and
      advantages and concerns regarding the use of breast shields in girls undergoing
      cardiac CT imaging.

PMID- 21847737
TI  - Advances in pediatric body MRI.
AB  - MRI offers an alternative to CT, and thus is central to an ALARA strategy.
      However, long exam times, limited magnet availability, and motion artifacts are
      barriers to expanded use of MRI. This article reviews developments in pediatric
      body MRI that might reduce these barriers: high field systems, acceleration,
      navigation and newer contrast agents.

PMID- 21847736
TI  - Newer CT applications and their alternatives: what is appropriate in children?
AB  - Innovations in image acquisition and reconstruction technologies have greatly
      expanded the range of CT applications available in the routine clinical setting.
      CT images of sub-millimeter resolution can now be acquired of entire body regions
      in a few seconds or even sub-second time, allowing depiction of fine anatomical
      detail uncompromised by motion artifact. With sophisticated visualization
      software, image data can be processed into multiplanar, volume-rendered, cine and
      other formats to better display anatomical abnormalities and facilitate newer
      applications such as CT angiography, enterography, urography,
      tracheobronchography and cardiac CT. Newer applications including dual-energy
      material decomposition CT are furthering the transition of CT from a purely
      morphological to a combined anatomical, functional and metabolic imaging
      technique. These newer applications have largely been pioneered in adult
      populations, and heightened concern of the risk of carcinogenesis from ionizing
      radiation tempers dissemination of their use in children. Similar information can
      often be gleaned from alternative imaging modalities without ionizing radiation
      exposure, such as MRI and US, and what is most appropriate in children will
      depend on relative diagnostic efficacy, cost, availability and local expertise.

PMID- 21847738
TI  - Ultrasound body applications in children.
AB  - A major goal of imaging is to obtain the correct examination to answer the
      clinical questions with the lowest possible radiation exposure. While CT
      examination provides essential information in many cases, other modalities that
      do not entail ionizing radiation exposure may be appropriate substitutes either
      as an initial screening study or as an alternative to CT. US has become a
      valuable imaging tool in children encompassing many different clinical scenarios.
      This manuscript highlights some of the less well-accepted applications of US as
      the first imaging study in pediatric patients, especially in the emergency room
      environment. These include evaluation of suspected appendicitis, abdominal mass,
      pleural effusion/empyema, thymic abnormality vs. mediastinal mass and extremity
      soft-tissue mass or vessel patency. Adoption of US imaging as a problem-solving
      tool for issues such as these requires appropriate allocation of resources to
      ensure high-quality performance and interpretation of pediatric US studies around
      the clock.

PMID- 21847739
TI  - CT utilization--trends and developments beyond the United States' borders.
AB  - There has been an exponential rise in the use of CT during the last 25 years,
      with similar trending of data from regions across the world. However, variability
      in levels of utilization and patterns of practice in both adult and pediatric
      populations can be identified. Multiple technical, health care, regulatory and
      cultural factors are shaping our use of this modality. Surveys of pediatric CT
      dose are now available from several countries with the development of proposed
      diagnostic reference levels. Challenges of this process will be discussed. This
      short presentation is not intended as a comprehensive review of the
      infrastructure and numerous advances in pediatric CT radiation protection
      occurring around the world but aims to highlight a few aspects.

PMID- 21847740
TI  - Getting it right: are regulation and registries for CT radiation dose in children
      the answer?
AB  - Recently, the state of California enacted a law requiring radiologists to record
      the radiation dose that each patient receives for a CT scan. Failure to do so is
      penalized by law. This law becomes effective in July 2012. By July 2013, every
      facility that performs CT scans must become accredited by one of three
      professional groups. This report discusses the role that legislation is playing
      in the practice of medicine in regard to CT practice. Inherent in this discussion
      is the assumption that pediatric radiologists know the right dose that a child
      should receive for a specific clinical indication. But do we really know the
      answer to this? Compared to the European radiology community, the United States
      radiology community lags in this regard. This paper defines diagnostic reference
      levels (DRL) and reviews the history of DRL in the United States compared to that
      in the European community and the progress by the American College of Radiology's
      National Radiology Data Registry (NRDR) to establish national registries. The
      establishment of the first pediatric Quality Improvement Registry in CT Scans in
      Children (QuIRCC) and its progress to date will be discussed.

PMID- 21847741
TI  - The role of CT in professionalism: accreditation, certification and the welfare
      of our children.
AB  - Defining, measuring and promoting professionalism in medicine, including
      radiology, has been increasingly emphasized by organizations such as ACGME, the
      ACR and ABR. It is clear that we as imaging experts have as an ultimate
      responsibility the welfare of our patients. This is the essence of
      professionalism, and major societies such as the ACR, ABR and RSNA are embracing
      professionalism through ongoing safety and training efforts. Some of those
      efforts in accreditation of equipment and certification of medical professionals
      will be discussed.

PMID- 21847743
TI  - Skeletal Radiology turns 40.

PMID- 21847744
TI  - The future of MSK interventions.

PMID- 21847745
TI  - The osteoclast--what's new?
AB  - Bone resorption is required for skeletal modelling during bone growth and for
      mineral homeostasis and bone remodelling throughout life. Osteoclasts are
      multinucleated cells that are uniquely specialised to carry out this
      physiological bone resorption. As osteolysis is a feature of most diseases of
      bone and joint, osteoclasts also play a role in pathological bone resorption, the
      extent of which is a function of the cellular and molecular mechanisms that
      govern their formation and function.

PMID- 21847746
TI  - Benign notochordal lesions of the axial skeleton: a review and current appraisal.
AB  - At the 1996 meeting of the International Skeletal Society, an idea was put forth
      that there existed symptomatic lesions of the axial skeleton, morphologically
      different from chordoma, that were consistent with benign notochordal remnants
      (rests). A review of the embryological basis for this concept is made, along with
      an analysis of these lesions, termed giant notochordal rests or benign
      notochordal cell tumors, that have been reported in the intervening 15 years,
      with a commentary on their relationship, if any, to chordoma.

PMID- 21847747
TI  - The impact of MRI on the clinical management of inflammatory arthritides.
AB  - In the past two decades, MRI has gained a major role in research and clinical
      management of patients with inflammatory arthritides, particularly in
      spondyloarthritis (SpA), rheumatoid arthritis (RA), and osteoarthritis (OA). MRI
      is regarded as the most sensitive imaging modality for detecting early SpA in
      young patients with inflammatory back pain and normal radiographs of the
      sacroiliac joints. The recently published Assessment of SpondyloArthritis
      International Society classification criteria for axial SpA include for the first
      time a positive MRI demonstrating sacroiliitis as an imaging criterion indicative
      of SpA together with at least one clinical feature of SpA. Recent data show that
      systematic assessment of sacroiliitis displayed on MRI has much greater
      diagnostic utility than previously reported and highlight the diagnostic
      relevance of structural lesions. In RA, MRI has predictive value for the
      development of disease in new onset undifferentiated arthritis, and MR pathology
      at disease onset is a highly significant predictor of radiographic erosions.
      Consequently MRI has been credited with an important role in the new ACR/EULAR
      2010 classification criteria for RA. In OA, bone marrow edema (BME) and synovitis
      may serve as biomarkers in interventional trials. Treatment interventions
      targeting BME and synovitis observed on MRI in inflammatory arthritides may have
      a disease-modifying effect as these lesions are potentially reversible and have
      been shown to be associated with structural progression. Research should focus on
      the prognostic significance of MRI lesions in larger cohorts and whether adding
      MRI to routine care improves clinical and radiographic outcome in patients with
      inflammatory arthritides.

PMID- 21847748
TI  - Imaging of lumbar degenerative disk disease: history and current state.
AB  - One of the most common indications for performing magnetic resonance (MR) imaging
      of the lumbar spine is the symptom complex thought to originate as a result of
      degenerative disk disease. MR imaging, which has emerged as perhaps the modality
      of choice for imaging degenerative disk disease, can readily demonstrate disk
      pathology, degenerative endplate changes, facet and ligamentous hypertrophic
      changes, and the sequelae of instability. Its role in terms of predicting natural
      history of low back pain, identifying causality, or offering prognostic
      information is unclear. As available modalities for imaging the spine have
      progressed from radiography, myelography, and computed tomography to MR imaging,
      there have also been advances in spine surgery for degenerative disk disease.
      These advances are described in a temporal context for historical purposes with a
      focus on MR imaging's history and current state.

PMID- 21847749
TI  - Bisphosphonates in the treatment of osteoporosis: a review of their contribution
      and controversies.
AB  - The bisphosphonates have revolutionized the therapy of osteoporosis, particularly
      the prevention of vertebral and hip fractures. The development of tools for
      defining absolute fracture risk facilitates their targeting to appropriate, at
      risk individuals. Prescribers need to be aware of their common side effects
      (gastrointestinal intolerance with oral dosing and flu-like illness following
      intravenous use). Whether these agents carry a real risk of other problems such
      as osteonecrosis of the jaw and subtrochanteric fractures remains uncertain at
      the present time. If the association of these problems with bisphosphonates is
      real, it is important that the major therapeutic benefits that can accrue from
      bisphosphonates' appropriate targeted use are not lost as a result of the anxiety
      concerning these extremely rare adverse events.

PMID- 21847751
TI  - The development and clinical applications of musculoskeletal ultrasound.
AB  - Musculoskeletal ultrasound has come a long way in 40 years. Reflecting changes in
      computer technology, ultrasound equipment has developed from machines that have
      filled examination rooms with mechanical probes linked by hinged arms for spatial
      localisation, to high-resolution machines that are the size of laptops using
      compact hand-held probes designed for both external and internal imaging.

PMID- 21847752
TI  - Challenges and opportunities for imaging journals: emerging from the shadows.
AB  - In this article, we will discuss the challenges and opportunities for imaging
      journals in the next decades. These include: the importance of optimizing online
      communication to enhance exchange of ideas in the sciences and the necessity to
      facilitate the development of quantitative tools that will aid in risk
      stratification, diagnosis, monitoring of therapy, and disease surveillance in an
      era of "P4 medicine". Journals will also need to promote the evidence-based
      evaluation of promising technologies so that the resources expended in healthcare
      may be most effectively used.

PMID- 21847753
TI  - Hand foot and mouth disease due to enterovirus 71 in Malaysia.
AB  - Hand foot and mouth disease is a febrile sickness complex characterized by
      cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence
      of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. The
      illness is caused by a number of enteroviruses with coxsackievirus A16 and
      enterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs
      to the species Human enterovirus A under the genus Enterovirus within the family
      Picornaviridae. EV71 has been associated with an array of clinical diseases
      including hand foot and mouth disease (HFMD), aseptic meningitis, encephalitis
      and poliomyelitis-like acute flaccid paralysis. A large outbreak of HFMD due to
      highly neurovirulent EV71 emerged in Malaysia in 1997, and caused 41 deaths
      amongst young children. In late 2000, a recurrence of an outbreak of HFMD
      occurred in Malaysia with 8 fatalities in peninsular Malaysia. Outbreak of HFMD
      due to EV71 recurred in 2003 with an unknown number of cases and mortalities. A
      similar outbreak of HFMD with 2 recorded deaths in young children occurred in
      peninsular Malaysia in late 2005 and this was followed by a larger outbreak in
      Sarawak (Malaysian Borneo) with 6 reported fatalities in the early part of 2006.
      The current on-going outbreak of HFMD started in peninsular Malaysia in
      epidemiological week 12 of 2010. As with other HFMD outbreaks in Malaysia, both
      EV71 and CA16 were the main aetiological viruses isolated. In similarity with the
      HFMD outbreak in 2005, the isolation of CA16 preceded the appearance of EV71.
      Based on the VP1 gene nucleotide sequences, 4 sub-genogroups of EV71 (C1, C2, B3
      and B4) co-circulated and caused the outbreak of hand, foot and mouth disease in
      peninsular Malaysia in 1997. Two sub-genogroups (C1 and B4) were noted to cause
      the outbreak in 2000 in both peninsular Malaysia and Sarawak. EV71 of sub
      genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak
      in 2003. In the 2005 outbreak, besides the EV71 strains of sub-genogroup C1, EV71
      strains belonging to sub-genogroup B5 were isolated but formed a cluster which
      was distinct from the EV71 strains from the sub-genogroup B5 isolated in 2003.
      The four EV71 strains isolated from clinical specimens of patients with hand,
      foot and mouth disease in the Sarawak outbreak in early 2006 also belonged to sub
      genogroup B5. Phylogenetic analysis of the VP1 gene suggests that the EV71
      strains causing the outbreak in Sarawak could have originated from peninsular
      Malaysia. Epidemiological and molecular data since 1997 show the recurrence of
      HFMD due to EV71 in Malaysia every 2 to 4 years. In each of the past outbreaks,
      more than one sub-genogroup of the virus co-circulate.

PMID- 21847750
TI  - The evolution of articular cartilage imaging and its impact on clinical practice.
AB  - Over the past four decades, articular cartilage imaging has developed rapidly.
      Imaging now plays a critical role not only in clinical practice and therapeutic
      decisions but also in the basic research probing our understanding of cartilage
      physiology and biomechanics.

PMID- 21847754
TI  - Epidemiology and mutational analysis of global strains of Crimean-Congo
      haemorrhagic fever virus.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality.
      Cases are reported in several countries in Africa, Europe, the Middle East, and
      Asia. Phylogenetic analyses based on the virus S (nucleocapsid), M
      (glycoprotein), and L (polymerase) genome segments sequences indicate distinct
      geographic lineages exist but their specific genetic characteristics require
      elucidation. In this work we collected all full length S segment sequences and
      generated a phylogenetic tree based on the alignment of these 62 samples. We then
      analyzed the alignment using entries from AAIndex, the Amino Acid Index database,
      to identify amino acid mutations that performed significant changes in charge,
      pka, hydropathy and side chain volume. Finally, we mapped these changes back to
      the tree and alignment to identify correlated mutations or sites that
      characterized a specific lineage. Based on this analysis we are able to propose a
      number of sites that appear to be important for virus function and which would be
      good candidates for experimental mutational analysis studies.

PMID- 21847755
TI  - Putative phosphorylation sites on WCA domain of HA2 is essential for Helicoverpa
      armigera single nucleopolyhedrovirus replication.
AB  - Protein phosphorylation is one of the most common post-translational modification
      processes that play an essential role in regulating protein functionality. The
      Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) orf2-encoded
      nucleocapsid protein HA2 participates in orchestration of virus-induced actin
      polymerization through its WCA domain, in which phosphorylation status are
      supposed to be critical in respect to actin polymerization. In the present study,
      two putative phosphorylation sites ((232)Thr and (250)Ser) and a highly conserved
      Serine ((245)Ser) on the WCA domain of HA2 were mutated, and their phenotypes
      were characterized by reintroducing the mutated HA2 into the HearNPV genome.
      Viral infectivity assays demonstrated that only the recombinant HearNPV bearing
      HA2 mutation at (245)Ser can produce infectious virions, both (232)Thr and
      (250)Ser mutations were lethal to the virus. However, actin polymerization assay
      demonstrated that all the three viruses bearing HA2 mutations were still capable
      of initiating actin polymerization in the host nucleus, which indicated the
      putative phosphorylation sites on HA2 may contribute to HearNPV replication
      through another unidentified pathway.

PMID- 21847756
TI  - Rapid and sensitive detection of PRRSV by a reverse transcription-loop-mediated
      isothermal amplification assay.
AB  - A real-time monitoring reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay was developed for the sensitive and specific
      detection of prototypic, prevalent North American porcine reproductive and
      respiratory syndrome virus (PRRSV) strains. As a higher sensitivity and
      specificity method than reverse transcription polymerase chain reaction (RT-PCR),
      the RT-LAMP method only used a turbidimeter, exhibited a detection limit
      corresponding to a 10(-4) dilution of template RNA extracted from 250 MUL of
      10(5) of the 50% tissue culture infective dose (TCID(50)) of PRRSV-containing
      cells, and no cross-reactivity was observed with other related viruses including
      porcine circovirus type 2, swine influenza virus, porcine rotavirus and classical
      swine fever virus. From forty-two field samples, 33 samples in the RT-LAMP assay
      was detected positive, whereas three of which were not detected by RT-PCR.
      Furthermore, in 33 strains of PRRSV, an identical detection rate was observed
      with the RT-LAMP assay to what were isolated using porcine alveolar macrophages.
      These findings demonstrated that the RT-LAMP assay has potential clinical
      applications for the detection of highly pathogenic PRRSV isolates, especially in
      developing countries.

PMID- 21847757
TI  - Characterization and diagnostic use of a monoclonal antibody for VP28 envelope
      protein of white spot syndrome virus.
AB  - The gene encoding the VP28 envelope protein of White spot syndrome virus (WSSV)
      was cloned into expression vector pET-30a and transformed into the Escherichia
      coli strain BL21. After induction, the recombinant VP28 (rVP28) protein was
      purified and then used to immunize Balb/c mice for monoclonal antibody (MAb)
      production. It was observed by immuno-electron microscopy the MAbs specific to
      rVP28 could recognize native VP28 target epitopes of WSSV and dot-blot analysis
      was used to detect natural WSSV infection. Competitive PCR showed that the viral
      level was approximately 10(4) copies/mg tissue in the dilution of gill homogenate
      of WSSV-infected crayfish at the detection limit of dot-blot assay. Our results
      suggest that dot-blot analysis with anti-rVP28 MAb could rapidly and sensitively
      detect WSSV at the early stages of WSSV infection.

PMID- 21847758
TI  - Application of GP5 protein to develop monoclonal antibody against porcine
      reproductive and respiratory syndrome virus.
AB  - In this study, a panel of monoclonal antibodies (mAbs) against Porcine
      reproductive and respiratory syndrome virus(PRRSV), named as 8C9 and4B4, were
      produced by fusing SP2/0 myeloma cells and spleen cells of BALB/c mice immunized
      with the PRRSV (TCID(50)=5.5), screened by the indirect ELISA and subjected to
      several limiting dilutions. mAbs were then identified by biological
      characterization. Among the two fusion cell strains, 8C9 belonged to the IgG1
      subclass and 4B4 belonged to the IgG2a subclass. The titers in cell culture
      supernatant and abdomen liquor reached to 1:10(4)and 1:10(5), respectively. The
      specificity test indicated that the two cells had specific reactions for the
      PRRSV and GP5 protein respectively, and no reaction with Classical swine fever
      virus (CSFV) or Swine vesicular disease virus (SVDV). The molecular weights of
      the heavy chain and light chain were about 45.0 kDa and 25.0 kDa, respectively.
      In neutralization activity tests, the results showed that the prepared mAb 4B4
      can protect 50% of cells with no CPE in dilution up to 1:512, but mAB 8C9 has no
      neutralization activities to PRRSV.

PMID- 21847759
TI  - Develope monoclonal antibody against foot-and-mouth disease virus A type.
AB  - In order to develop an anti-FMDV A Type monoclonal antibody (mAb), BABL/c mice
      were immunized with FMDV A type. Monoclonal antibodies (mAbs) 7B11 and 8H4
      against Foot-and-mouth disease virus (FMDV) serotype A were produced by fusing
      SP2/0 myeloma cells with splenocyte from the mouse immunized with A/AV88. The
      microneutralization titer of the mAbs 7B11 and 8H4 were 1024 and 512,
      respectively. Both mAbs contain kappa light chains, the mAbs were IgG1. In order
      to define the mAbs binding epitopes, the reactivity of these mAbs against A Type
      FMDV, were examined using indirect ELISA, the result showed that both mAbs
      reacted with A Type FMDV. These mAbs may be used for further vaccine studies,
      diagnostic methods, prophylaxis, etiological and immunological research on FMDV.
      Characterization of these ncindicated that prepared anti-FMDV A mAbs had no cross
      reactivity with Swine Vesicular Disease (SVD) or FMDV O, Asia1 and C Type
      antigens. Their titers in abdomen liquor were 1:5*10(6) and 1:2*10(6),
      respectively. 7B11 was found to be of subtype IgG(1), 8H4 was classified as
      IgG(2b) subtype. The mAbs prepared in this study, are specific for detection of
      FMDV serotype A, and is potentially useful for pen-side diagnosis.

PMID- 21847760
TI  - Bioinformatic analysis of BBTV satellite DNA in Hainan.
AB  - Banana bunchy top virus (BBTV), family Nanaviridae, genus Babuvirus, is a single
      stranded DNA virus (ssDNA) that causes banana bunchy top disease (BBTD) in banana
      plants. It is the most common and most destructive of all viruses in these plants
      and is widespread throughout the Asia-Pacific region. In this study we isolated,
      cloned and sequenced a BBTV sample from Hainan Island, China. The results from
      sequencing and bioinformatics analysis indicate this isolate represents a
      satellite DNA component with 12 DNA sequences motifs. We also predicted the
      physical and chemical properties, structure, signal peptide, phosphorylation,
      secondary structure, tertiary structure and functional domains of its encoding
      protein, and compare them with the corresponding quantities in the replication
      initiation protein of BBTV DNA1.

PMID- 21847761
TI  - Hemorrhagic fever with renal syndrome complicated by orchitis.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is a disease caused by viruses of
      the family Bunyaviridae, genus Hantavirus. HFRS from Dobrava virus (DOBV) is a
      seldom reported disease in Albania. Clinically HFRS is manifested as mild,
      moderate, or severe. Therefore, the number of cases of Hantavirus' infection may
      be underestimated, and should be included in the differential diagnosis of many
      acute infections, hematologic diseases, acute abdominal diseases and renal
      diseases complicated by acute renal failure. We report here an atypical
      presentation of HFRS from Dobrava virus complicated by orchitis with a positive
      outcome.

PMID- 21847762
TI  - Best practices in systems interventions to reduce the burden of fractures.

PMID- 21847763
TI  - Improving osteoporosis care through multimodal interventions: insights from the
      University of Alabama at Birmingham Center for Education and Research on
      Therapeutics.
AB  - Despite the many advances in scientific research over the last several decades,
      cutting edge technologies and therapeutics often take many years to find their
      way into widespread use. The dissemination and uptake of best practices into
      clinical care is sometimes a neglected component of research that is essential to
      improve the population's health. Type 2 translational research, sometimes called
      "Proof in Practice Research," seeks to maximize the yield of what has been
      learned from the bench and from carefully controlled clinical trials and to
      extend those benefits to a larger population. One aspect of type 2 translational
      research, sometimes called evidence implementation or implementation science,
      applies what has been learned about clinical medicine to achieve best practices
      across providers and health systems. This article describes evidence
      implementation as applied to osteoporosis care, drawing from several published or
      ongoing studies to illustrate challenges and potential solutions in improving the
      quality of osteoporosis care.

PMID- 21847764
TI  - Perspectives on pre-fracture intervention strategies: the Geisinger Health System
      Osteoporosis Program.
AB  - In its first decade, the goals of the Geisinger Health System Osteoporosis
      Program at its inception were to increase awareness, diagnosis, and treatment of
      osteoporosis and to monitor predefined outcomes. The program was innovative in
      that it crossed specialties and regions and used guidelines in an effective
      manner. In addition, success in reducing hip fracture and cost were demonstrated,
      and it remains one of the few programs today that has done so, as reported by
      Newman et al. (Osteoporos Int 14:146-151, 2003). The osteoporosis program has now
      moved from a provider and allied provider empowerment focus to reorganizing our
      thoughts about how to best manage osteoporosis care across our healthcare system
      by defining and acting on four major osteoporosis care gaps: (1) at-risk patients
      do not get tested, (2) tested patients are not accurately risk assessed, (3) high
      risk patients do not get treated, and (4) treated patients are not adherent.
      Results of current internal programs and future steps are discussed.

PMID- 21847765
TI  - Fracture prevention in Kaiser Permanente Southern California.
AB  - The Kaiser Permanente Healthy Bones Program has used a systematic approach to
      address the osteoporosis/fracture care gaps. The article discusses the ten-step
      processes that utilize information technology and care managers to identify, risk
      stratify, treat, and then track our patients with care gaps. This program has led
      to 40+% reduction in the expected number of hip fractures in 2009 that we
      attribute to the increase in DXA screening followed by appropriate osteoporosis
      treatment.

PMID- 21847766
TI  - Changing health behaviors with social marketing.
AB  - Social marketing uses marketing techniques to promote healthy attitudes and
      behaviors. As in traditional marketing, the development and implementation of
      social marketing programs is based on the four P's: product, price, place, and
      promotion, but it also incorporates the partnership and participation of
      stakeholders to enhance public health and engage policy makers. INTRODUCTION: The
      "product" in social marketing is generally a behavior, such as a change in
      lifestyle (e.g., diet) or an increase in a desired health practice (e.g.,
      screening). In order for people to desire this product, it must offer a solution
      to a problem that is weighed with respect to the price to pay. The price is not
      just monetary, and it often involves giving something up, such as time (e.g.,
      exercising) or a wanted, satisfying behavior (e.g., smoking). METHODS: In its
      development phase, social marketing incorporates qualitative methods to create
      messages that are powerful and potentially effective. The implementation of the
      programs commonly involves mass campaigns with advertisement in various media.
      RESULTS: There have been a few social media campaigns targeting bone health that
      have been disseminated with substantial outreach. However, these have not been
      systematically evaluated, specifically with respect to change in behavior and
      health outcomes. CONCLUSIONS: Future campaigns should identify target behaviors
      that are amenable to change such as bone mass measurement screening or exercise.
      Audience segmentation will be crucial, since a message for young women to
      increase peak bone mass would be very different from a message for older
      individuals who have just experienced a fracture. Campaigns should involve key
      stakeholders, including policy makers, health providers, and the public. Finally,
      success must be carefully evaluated, not just by the outreach of the campaign,
      but also by a change in relevant behaviors and a decrease in deleterious health
      outcomes.

PMID- 21847767
TI  - Postfracture interventions disseminated through health care and drug insurers:
      attempting to integrate fragmented health care delivery.
AB  - Osteoporosis care after a fracture is often suboptimal. Suboptimal treatment
      seems to be most common in fragmented health care systems. We examined the
      literature to assess possible causes for suboptimal postfracture osteoporosis
      care within fragmented health care systems. The review of the literature did not
      attempt to meta-analyze prior studies. We found several possible methods for
      improving postfracture osteoporosis care in a fragmented health care system.
      These include changes in health care financing, application of information
      technology, incorporation of case management, the use of system champions, and
      dissemination of performance measures. The strengths and weaknesses of each of
      these potential levers for improvement were explored. Postfracture osteoporosis
      care is sub-optimal and challenging to improve in fragmented health care delivery
      systems.

PMID- 21847768
TI  - A T-2 translational research perspective on interventions to improve post
      fracture osteoporosis care.
AB  - The objectives of this paper are to: quickly outline the extent of the care gap
      in osteoporosis; define T-2 (knowledge) translation and its relationship to
      quality improvement; discuss the barriers to best practice in osteoporosis care
      after a fracture; convey the importance of rigor in design and evaluation of
      translational interventions by drawing upon examples from the broader literature;
      describe in some detail a series of post-fracture intervention trials conducted
      in Alberta, Canada; and make some conclusions specifically about osteoporosis
      interventions and more generally about T-2 translational research.

PMID- 21847769
TI  - It is time for everyone to own the bone.
AB  - The current status of the population's bone health has caused considerable
      concern in the USA and around the world. In keeping with that situation, the US
      Surgeon General issued a special report on Bone Health and Osteoporosis in 2004
      calling attention to a rapidly increasing healthcare problem especially linked to
      a growing and aging population base. The report specifically cited the medical
      profession's failure to treat the underlying osteoporosis in elderly individuals
      with fragility fractures with a 20% treatment rate as the norm. It was noted that
      an individual fracture was a sentinel event that provided a "teachable moment"
      for the patient in order to prevent future fractures. Additional statistics
      revealed the annual total number of fragility fractures, more than two million,
      exceeded the combined annual total incidence of stroke, myocardial infarction,
      and breast cancer. Realizing that the American Heart Association and the
      cardiology community had a successful US national program encouraging the use of
      beta blockers in patients after myocardial infarction in order to prevent
      recurrences, the American Orthopaedic Association (AOA) embarked on a course
      leading to the development of a program to improve bone healthcare in elderly
      patients with fragility fractures. The cardiology project, "Get With The
      Guidelines" (GWTG), included a registry in order to document improvement in
      cardiac patient care. Therefore, the AOA, a leadership group of orthopaedic
      surgeons, decided it was time to engage the orthopaedic community in a quality
      improvement initiative patterned after GWTG. Thus, Own the Bone was created as a
      multidisciplinary program in order to engage patients and physicians from
      different specialties who might be involved with the bone health concerns of
      patients with fragility fractures. After the success of a pilot study from 2005
      to 2006, Own the Bone was launched as a US national quality improvement program
      in 2009. It involves a turnkey protocol, utilizing a web-based registry, in order
      to complete ten basic measures of patient care in patients 50 years and older
      with fragility fractures. Those measures center on information and counseling on
      nutrition, physical activity, lifestyle changes, diagnosis and treatment of
      osteoporosis, and communication to the patient and primary care physician,
      mentioning the need for osteoporosis care. While this project was initially meant
      to be implemented in a hospital setting, it can also be applied in an outpatient
      clinic or emergency care facility. The program continues to expand to numerous
      hospitals in many states with the support of a growing number of orthopedists and
      allied medical specialists interested in bone health and osteoporosis. Thus, Own
      the Bone is a systems-based, quality improvement initiative which provides many
      benefits for patients with fragility fractures and their treating physicians.

PMID- 21847770
TI  - A decade of system- and population-based osteoporosis care improvement.
AB  - The results of a 9-year osteoporosis clinical improvement project are reviewed,
      and the implications for secondary fracture prevention are discussed.

PMID- 21847771
TI  - Fracture Liaison Services: the UK experience.
AB  - Fracture Liaison Services (FLS) have been shown to deliver clinically and cost
      effective osteoporosis care for patients presenting to hospital with fragility
      fractures. During the first decade of the new millennium, a consensus emerged in
      the UK on the need for universal access to FLS. This presentation described
      constructive interactions between policy makers, professional organizations,
      patients and their associations, and pharmaceutical manufacturers that led to the
      incorporation of FLS into national policy and guidance.

PMID- 21847772
TI  - Systems-based approaches to osteoporosis and fracture care: policy and research
      recommendations from the workgroups.
AB  - Participants in the conference selected to attend two different working group
      sessions. The working groups discussed different perspectives of system-based
      approaches to osteoporosis and fracture care. The group on postfracture case
      management recommended that nurse case managers be used to improve communication
      among patients, orthopaedic surgeons, and those providing ongoing clinical care.
      The hospital working group discussed the impact of and barriers to improved
      postfracture management in the hospital setting. The health systems group
      emphasized the difference between a closed system in which long-term benefits of
      interventions were more likely to be appreciated than in fee for service systems.
      The health information technology group discussed the advantages and challenges
      of electronic health records. The working group on consumer and provider
      education discussed interventions for both primary and secondary prevention of
      fractures. Recommendations were produced by most groups for improving
      postfracture care.

PMID- 21847773
TI  - Which method of estimating renal function is the best predictor of mortality
      after coronary artery bypass grafting?
AB  - OBJECTIVES: Definitions of renal function in patients undergoing coronary artery
      bypass graft surgery (CABG) vary in the literature. We sought to investigate
      which method of estimating renal function is the best predictor of mortality
      after CABG. METHODS: We analysed the preoperative and postoperative renal
      function data from all patients undergoing isolated CABG from January 1998
      through December 2007. Preoperative and postoperative renal function was
      estimated using serum creatinine (SeCr) levels, creatinine clearance (CrCl)
      determined by the Cockcroft-Gault formula and the glomerular filtration rate (e
      GFR) estimated by the Modification of Diet in Renal Disease (MDRD) formula.
      Receiver operator characteristic (ROC) curves and area under the ROC curves were
      calculated. RESULTS: In 9987 patients, CrCl had the best discriminatory power to
      predict early as well as late mortality, followed by e-GFR and finally SeCr. The
      odds ratios for preoperative parameters for early mortality were closer to 1 than
      those of the postoperative parameters. CONCLUSIONS: Renal function determined by
      the Cockcroft-Gault formula is the best predictor of early and late mortality
      after CABG. The relationship between renal function and mortality is non-linear.
      Renal function as a variable in risk scoring systems such as the EuroSCORE needs
      to be reconsidered.

PMID- 21847774
TI  - National differences in screening programmes for cardiovascular risks could
      obstruct understanding of cardiovascular prevention studies in Europe.
AB  - INTRODUCTION: In North-West Europe, cardiovascular disease is still a major cause
      of death and despite several efforts (e.g. European guidelines and conferences)
      cardiovascular risk factors are still inconsistently diagnosed and treated.
      METHODS: We evaluated the first consultations of patients in two cardiovascular
      referral clinics in France and the Netherlands, while evaluating the differences
      in national guidelines and between the profiles of patients at their first
      consultation. RESULTS: Notable differences exist between the two locally used
      guidelines in their programmes of cardiovascular risk assessment and their
      definition of LDL-cholesterol target levels. With regard to the LDL-cholesterol
      levels, more patients are 'on target' when using the French guideline than when
      using the Dutch guideline. Evaluation of the patient's profile at first
      presentation showed that the LDL-cholesterol levels were significantly lower in
      the Dutch patients (n = 77) compared with the French patients (n = 119). Dutch
      patients used significantly more statins than French patients. CONCLUSION:
      Despite the small study population included in this study, we found that
      comparison of daily care (as part of a primary prevention programme) is rather
      difficult due to several national differences in the approach to patients. All
      these factors combined should be taken into account, when discussing and
      extrapolating results obtained from analysis of cardiovascular prevention
      programmes.

PMID- 21847776
TI  - [Liver imaging - an update].

PMID- 21847775
TI  - Proinflammatory CD14+CD16+ monocytes are associated with microinflammation in
      patients with type 2 diabetes mellitus and diabetic nephropathy uremia.
AB  - Diabetic nephropathy (DN) is a major cause of type 2 diabetes mellitus (T2DM)
      mortality. Innate immunity has been shown to be closely associated with the
      occurrence and progression of T2DM-associated complications. In this study, we
      investigated the expression of Toll-like receptor 4 (TLR4) and CD14(+)CD16(+)
      monocytes in patients with T2DM and DN patients with uremia and TLR4 response to
      lipopolysaccharide (LPS), and to further explore the potential effects of
      inflammatory immune response in T2DM and DN uremia. Thirty DN patients with
      uremia, 28 T2DM patients, and 20 healthy volunteers were enrolled for the
      determination of CD14(+)CD16(+) fluorescence intensity and TLR4 expression on
      monocytes by using peripheral blood flow cytometry. Serum C-reactive protein
      (CRP) level was determined by using the immunoturbidimetry. Peripheral blood
      mononuclear cells (PBMCs) were isolated and stimulated with LPS for 24 h.
      monocytes were collected to detect NF-kappaB p65 and phosphorylated STAT5(p
      STAT5) expressions by using Western blotting. Supernatants were sampled for the
      determination of interleukin-6 (IL-6) concentration by using ELISA. Compared to
      normal control, T2DM patients and DN uremic patients had a significantly higher
      CD14(+)CD16(+) fluorescence intensity, TLR4 expression, serum IL-6 and CRP level,
      whilst these biomarkers were more upregulated in DN uremic patients than in T2DM
      patients. Following the exposure to LPS, PBMCs showed a significant upregulation
      in NF-kappaB-p65 and p-STAT5 expression and a remarked increase in Supernatants
      IL-6 level, in a positive correlation with disease severity. Our results suggest
      that the disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in T2DM
      and DN uremic patients. Such immunological dysfunction may be related to the
      activation of TLR4/NF-kappaB and STAT5 signaling pathways underlying the immune
      abnormalities of CD14(+)CD16(+) monocytes.

PMID- 21847777
TI  - [Latest developments in ultrasound of the liver].
AB  - Abdominal ultrasound (US) is often the first-line imaging modality used to assess
      focal liver lesions. Due to various new gray-scaled US techniques, such as tissue
      harmonic imaging (THI), spatial compounding technique and speckle reduction
      technique, as well as contrast-enhanced techniques, abdominal ultrasound nowadays
      has great potential regarding detection and characterization of focal liver
      lesions. Furthermore, image fusion with computed tomography (CT), magnetic
      resonance imaging (MRI) and 3D ultrasound will most likely help to improve
      clinical management before and after interventional procedures. This article
      illustrates the principles and clinical impact of recently developed techniques
      in the field of ultrasound.

PMID- 21847780
TI  - [Skeletal trauma during the growing period. Radiological diagnostics].
AB  - Bone fractures in childhood are a common occurrence. A differentiated assessment
      of fractures is of great importance for the diagnostics, therapy planning and
      estimation of the prognosis. This review article explains the most important
      characteristics of skeletal trauma in childhood. Skeletal development, the
      mechanisms of fracture healing and growth disorders after injury to the
      epiphyseal plates and classification of fractures will be discussed and typical
      bone fractures in children and the pitfalls in X-ray diagnostics are
      demonstrated.

PMID- 21847779
TI  - [Malignant focal liver lesions].
AB  - Focal liver lesions are a very common occurrence. The detection and
      differentiation of such lesions is particularly important for the management of
      oncology patients and is a core task for radiology. The early and conclusive
      detection of malignant liver processes in a cost-efficient manner and with a low
      radiation dose for the patient requires systematic and skillful use of the
      various radiological methods. This review explains the application of current
      radiological methods for the detection and differentiation of malignant liver
      lesions and the typical appearance of the most commonly found liver malignancies.

PMID- 21847782
TI  - [The melanocyte and the eye: a review with special emphasis on the cornea].
AB  - BACKGROUND: Various publications especially from the field of dermatology have
      indicated in the recent years that the melanocyte is a "multitalent" with-
      besides UV-protection--(neuro-)humoral and immunological functions. Moreover, the
      melanocyte could play a role as a scavenger of free radicals or in pressure
      perception, so that it could even perhaps be part of the "intraocular pressure
      sensor". It is generally assumed that the cornea is devoid of melanocytes under
      physiological conditions. However, to the best of our knowledge a systematic
      investigation with a larger quantity of specimens has not been performed thus
      far. METHODS: 103 corneal specimens (whole eyes, corneal explants with different
      corneal diseases, corneoscleral donor buttons) and 13 pterygia (corneal part)
      were studied immunohistochemically using the monoclonal antibody Melan A which is
      specific for melanocytes. RESULTS: In healthy cornea melanocytes are found in the
      limbal area. In the corneal periphery, up to 1 mm distant from the limbus, the
      melanocytes disappear so that the mid-peripheral and the central epithelium of
      the cornea are devoid of melanocytes. Under pathological conditions (dystrophies,
      scars, ulcers) there is only exceptionally an invasion of melanocytes into the
      mid-peripheral corneal epithelium. The central epithelium almost always remains
      free of melanocytes even in various corneal diseases. In more than 50% of the
      pterygia melanocytes can be found in the epithelium. CONCLUSIONS: Under certain,
      pathological conditions melanocytes can settle in more central regions of the
      corneal epithelium. Thus, the very few "corneal melanomas" described in the
      literature could have theoretically developed within the cornea itself (and not
      within the limbus). Obviously, the cornea possesses mechanisms to inhibit
      centripetal migration of melanocytes perhaps via a (still hypothetic) "corneal
      melanocyte suppression factor" ("CoMeSuF"). To identify this factor will be the
      task for the coming years. If this factor is really existent it could possibly
      serve as a therapy for melanocytic proliferations (melanomas).

PMID- 21847783
TI  - [Relative afferent pupillary defect in glaucoma].
AB  - BACKGROUND: The aim of this retrospective study was to estimate the frequency of
      relative afferent pupillary defect (RAPD) in glaucoma and whether its occurrence
      relates to the severity of the visual field defect and its side asymmetry as
      detected by standard automated perimetry. PATIENTS AND METHODS: Among patients
      with primary open angle glaucoma examined at the glaucoma unit of our university
      eye hospital patients were identified in whom a swinging-flashlight test as part
      of their routine examination was carried out. The central 30 degrees  visual
      field was examined by means of static perimetry using the Tubinger Automatic
      Perimeter or the Octopus Perimeter. The visual field findings and their side
      difference were compared between patients with and without RAPD by means of the
      Wilcoxon rank-sum test. RESULTS: After having taken into consideration the
      inclusion criteria, 100 glaucoma patients were included in the study, 34 of them
      had an RAPD (34 %). For the visual field analysis only the data of 85 patients,
      who received the same perimetric strategy, were used. 25 of them had an RAPD (29
      %). The calculated visual field scores in patients with RAPD were significantly
      higher than those in patients without RAPD (p < 0.01), that means their visual
      field loss was generally more advanced. Also the side difference in visual field
      of both eyes was significantly greater in patients with RAPD (p < 0.01). A
      receiver operating characteristics (ROC) curve showed that the side difference in
      visual field defect is a good predictor for RAPD with an area under curve (AUC)
      of 0.81. CONCLUSION: RAPD can be diagnosed in about one third of patients with
      primary open angle glaucoma. It can be found especially with more advanced visual
      field defects and visual field defects with greater side asymmetry. Its absence
      does not mean that there is no visual field defect at all. We advise to include
      the swinging-flashlight test in glaucoma diagnostics.

PMID- 21847784
TI  - [Dynamic vision of sportsmen with different requirement profiles for the visual
      apparatus].
AB  - AIM OF STUDY: In particular, in the quick ball and racket games a good dynamic
      seeing is required  . The afferent dynamic seeing occurs via the retiina which
      mediates the stimuli for efferent dynamic seeing  . The aim of this study was to
      examine the dynamic visual acuity of sportsmen from sports with different demands
      on their dynamic seeing (DS). METHODS: 19 sports students took part in the study.
      10 subjects participated in coached team sports (group I) and 9 remaining
      performed individual sports (group II). The DS was assessed by means of the
      Dusseldorfer test for dynamic seeing of Wist   which was performed twice on one
      day. RESULTS: The DS of the two groups in the first study did not differ (right
      eye 95.7 +/- 10.6 % in group I vs. 94.3 +/- 6.9 % in group II and left eye 97.6
      +/- 4.8 % vs. 95.3 +/- 5.6 %; p >= 0.05). Also the second study there was no
      different in DS for the two groups (right eye 98.3 +/- 2.6 % vs. 93.8 +/- 8.0 %
      and left eye 99.3 +/- 1.2 % vs. 95.6 +/- 7.0 %; p >= 0.05). DISCUSSION: Our
      hypothesis about a different DS in players of ball games compared with non-ball
      sport players could not be proved. It is to be critically noted that a
      generalization is not possible due to the small sample numbers. Because DS is a
      necessary precondition in ball games further studies should be concentrated on
      its trainability.

PMID- 21847785
TI  - [Hydrogelexpander as drug delivery system for antibiotics].
AB  - PURPOSE: The suitability of a high-hydrophilic osmotic self-inflating hydrogel
      expander consisting of a co-polymer of N-vinylpyrolidone and methyl methacrylate
      as a drug delivery system for antibiotics to prevent a postoperative infection
      was investigated in a laboratory setting. METHODS: The dry expanders were
      incubated in a 0.3 % solution of Ofloxacin or Tobramycin for 24 hours. The
      completely swollen expander had increased in volume from 0.3 mL to almost 3 mL
      (adsorbing 2.7 mL of the 0.3 % solution, i. e.,8.1 mg of Ofloxacin or Tobramycin,
      respectively). Addressing the elimination of both antibiotics, the concentrations
      in 15 mL elution medium (simulating the volume of the orbit in a newborn baby)
      were measured after 0.25, 1, 2, 6, 24, 48 and 72 hours of elution. 0.9 % sodium
      chloride (B. Braun Melsungen, Germany) was used as elution medium. To imitate
      fluid exchange due to blood perfusion in the surrounding tissue the medium was
      renewed after every sampling. For each substance 10 expanders were tested.
      Concentrations of antibiotic were determined by HPLC/UV for Ofloxacin and by
      using a specific fluorescence-polarisation immunoassay (Abbott TDx) for
      Tobramycin. RESULTS: Mean concentrations of Ofloxacin at 0.25, 1, 2, 6, 24, 48
      and 72 hours after beginning of the elution were 50.2, 46.8, 41.2, 75.4, 88.2,
      46.2 and 19.1 ug/mL, respectively. The cumulative amount of Ofloxacin eluted
      after 72 hours reached 68 % of the loading dose. The corresponding mean
      concentrations of Tobramycin were 38.8, 48.5, 40.5, 69.8, 88.7, 119.3 and 71.6
      ug/mL. The cumulative eluted amount was 88 %. CONCLUSIONS: The investigated
      hydrogel expanders soaked in 0.3 % antibiotic solution can store and later on
      release sufficient amounts of Ofloxacin or Tobramycin to produce antimicrobial
      effective concentrations in vitro in the surrounding environment. This principle,
      when used in a clinical setting, might help to eliminate post-implantation
      infection which is one of the major complications in clinical use.

PMID- 21847786
TI  - [Progressive visual loss and muscular weakness in a young patient].

PMID- 21847787
TI  - [Journal of Orthopedics and Trauma Surgery has changed the editorial staff].

PMID- 21847788
TI  - Sono-alkalization pretreatment of sewage sludge containing phthalate acid esters.
AB  - This work experimentally elucidates the efficiencies of sono-alkalization
      treatment on municipal sewage sludge. The total solids (TS) concentration of the
      sewage sludge was pre-adjusted at 29.7 g/L. Two parameters such as sodium
      hydroxide (NaOH) dosage and sonication time were considered by the central
      composite design (CCD) program to investigate the effect on the degradation of
      phthalate acid esters (PAEs) and solubilization of soluble chemical oxygen demand
      (SCOD). The mean concentrations of dibutyl phthalate (DBP), di-(2-ethylhexyl)
      phthalate (DEHP) and butyl benzyl phthalate (BBP) in the sewage sludge were 718,
      41 and 8 mg/kg dry weight sludge, respectively. Sono-alkalization process was
      effective on the degradation of DBP but worthless for DEHP and BBP. Overall
      degradation of DBP in sewage sludge was estimated to be 100% at the NaOH dosage
      of 68 m Mand sonication time of 2.2 min. Sono-alkalization was responsible for
      6,000 mg/L increase of SCOD based on the decrease of volatile solids in sewage
      sludge.

PMID- 21847789
TI  - High-temperature hydrodechlorination of ozone-depleting chlorodifluoromethane
      (HCFC-22) on supported Pd and Ni catalysts.
AB  - The hydrodechlorination of chlorodifluoromethane (HCFC-22) was performed by a
      catalytic reaction and noncatalytic thermal decomposition at high temperatures of
      400-800  degrees C. After 47 h of time-on-stream on a supported palladium (Pd)
      catalyst, the gas phase composition of difluoromethane (HFC-32) is 41.0%, with
      4.9% of the HCFC-22 remaining, indicating the conversion of up to 95.1% of HCFC
      22. The supported nickel catalyst's deactivation is significant as it exhibits
      the low conversion of HCFC-22 under the same reaction conditions. The
      deactivation of the catalyst is caused by the polymerization of adsorbed methyl
      radicals, which competes with the formation of HFC-32. With concentrated
      reactants at high reaction temperatures, there was an increase in the catalytic
      activity; however, unwanted tar, methane, and trifluoromethane (HFC-23) by
      products are also produced. The use of catalyst suppresses the formation of these
      by-products. Considering the compositions of the products of the catalytic and
      noncatalytic reactions, we demonstrate that the use of the supported-metal
      catalysts and hydrogen flow suppresses tar formation and lowers the required
      reaction temperature.

PMID- 21847790
TI  - Effect of substrate interaction on oxidation of methane and benzene in enriched
      microbial consortia from landfill cover soil.
AB  - The interaction of methane and benzene during oxidation in enriched methane
      oxidizing consortium (MOC) and in benzene-oxidizing consortium (BOC) from
      landfill cover soil was characterized. Oxidation of both methane and benzene
      occurred in the MOC due to the coexistence of bacteria responsible for benzene
      oxidation, as well as methanotrophs, whereas in the BOC, only benzene was
      oxidized, not methane. Methane oxidation rates in the MOC were decreased with
      increasing benzene/methane ratio (mol/mol), indicating its methane oxidation was
      inhibited by the benzene coexistence. Benzene oxidation rates in the MOC,
      however, were increased with increasing benzene/methane ratio. The benzene
      oxidation in the BOC was not affected by the coexistence of methane or by the
      ratio of methane/benzene ratio (mol/mol). No effect of methane or benzene was
      found on the dynamics of functional genes, such as particulate methane
      monooxygenase and toluene monooxygenase, in association with oxidation of methane
      and benzene in the MOC and BOC.

PMID- 21847791
TI  - Sorption of nonpolar neutral organic compounds to model aquifer sands:
      implications on blocking effect.
AB  - The use of a calibrated two-component model with a single blocking parameter for
      both adsorption onto mineral surfaces and partitioning into soil organic matter
      of two nonpolar sorbates (i.e., 1,2,4-trichlorobenzene and benzene) was evaluated
      by using several humic acid (HA)-coated sands with different fractions of organic
      carbon (f(oc)) ranging from 0.006 to 0.154%. Sorption of nonpolar sorbates to
      both untreated and heated sands was nearly linear due to the reduction of
      heterogeneous adsorption potential by strongly adsorbed vicinal water molecules
      over hydrophilic mineral surfaces. Sorption of nonpolar sorbates to the HA-coated
      sands was also essentially linear, and resulted from a combination of adsorption
      onto mineral surfaces and partitioning into soil organic matter, with the
      dominance of either contribution depending on the properties of the sorbents
      (e.g., f(oc)) and the sorbates (e.g., K(ow)). Contrary to the previous studies
      suggesting that surface area is the only variable affecting the magnitude of the
      adsorption coefficient onto modified high-surface-area clay minerals, the
      difference in adsorptive affinity of nonpolar sorbates onto modified mineral
      surfaces (i.e., K(S,c)) relative to that for pure mineral surfaces (i.e., K(S))
      also may be important for low-surface-area, coarse-grained model aquifer sands.
      However, the improvement in predicted sorption behavior by incorporating the
      blocking effect is insignificant for low-surface-area, coarse-grained model
      aquifer sands.

PMID- 21847792
TI  - Chemical composition of lake sediments along a pollution gradient in a Subarctic
      watercourse.
AB  - Sediment cores were collected from seven lakes in the Subarctic Pasvik
      watercourse, polluted by sewage waters and air emissions from the Pechenganickel
      Metallurgical Company, in order to study chemical composition and estimate the
      intensity of pollution by taking into account background concentration of
      elements and the vertical and spatial distribution of their contents in cores and
      surficial layers of sediments. Sediment samples were analysed by atomic
      absorption spectrophotometry for 18 elements (Ni, Cu, Co, Zn, Cd, Pb, Hg, As, Cr,
      Sr, Mn, Fe, Ca, Mg, Na, K, Al, P). Maximum concentrations of all investigated
      heavy metals (Ni, Cu, Co, Zn, Cd, Pb, Hg, As) were found in the surficial
      sediment layers of Lake Kuetsjarvi situated directly below the metallurgic
      smelters. Decreased contents of heavy metals were observed in surficial sediment
      layers further downstream in the Pasvik watercourse, although pollution remained
      rather high. Considerable increase in the contents of the heavy metals emitted
      into the atmosphere in significant amounts by the Pechenganickel Company (Ni, Cu,
      Co, Zn), was not observed in surficial sediment layers of lakes upstream in the
      watercourse polluted only by air contamination and household sewage, but
      substantial increase of the concentrations of chalcophile elements (Pb, Cd, Hg,
      As) was revealed. The increase in P contents towards the sediment surface in some
      lakes may suggest a development of eutrophication processes. Our studies reveal
      that the metallurgic processing of the Pechenganickel Company has resulted in
      comprehensive heavy metal pollution and contaminations of lakes sediments in the
      Inari-Pasvik watercourse. The pollution impact on the sediments is most severe in
      Lake Kuetsjarvi in the vicinity of the smelters, intermediate in lake localities
      in the main watercourse downstream the metallurgic enterprises and least in lake
      localities in the upstream part of the watercourse.

PMID- 21847793
TI  - Impaired glucose tolerance in mice lacking cellular prion protein.
AB  - OBJECTIVES: We previously demonstrated that the expression of cellular prion
      protein (PrPC) in islet [beta]-cells is suppressed in hyperglycemic rats
      suggesting a major role for PrPC in blood glucose regulation. To further
      characterize the function of PrPC in glucose homeostasis, we studied
      glucoregulation in PrPC knockout (PrPC KO) mice. METHODS: Glucose tolerance,
      insulin secretion, and insulin sensitivity were analyzed to assess
      glucoregulation in Zrch I PrPC KO and the C57BL/6 (control) mice.
      Immunohistochemistry and morphometry were used to measure [beta]-cell mass.
      RESULTS: Male PrPC KO mice had significantly increased blood glucose
      concentration 60, 120, and 180 minutes after intraperitoneal injection of glucose
      compared with C57BL/6 mice. Female PrPC KO mice showed a less pronounced
      phenotype of glucose intolerance. Evaluation of [beta]-cell mass, insulin and
      proinsulin deficiency, and insulin resistance in male mice revealed essentially
      no difference between PrPC KO and control mice. The only exception was an
      increase in serum insulin concentration in male PrPC KO mice 5 minutes after
      glucose injection. CONCLUSIONS: This report is the first to show that PrPC in
      [beta]-cells is involved in glucoregulation. A further understanding of the role
      of PrPC in regulating [beta]-cell function will provide valuable insight into the
      mechanisms of blood glucose regulation.

PMID- 21847795
TI  - Abstracts of the 8th EBSA (European Biophysical Societies Association) European
      Biophysics Congress. August 23-27, 2011. Budapest, Hungary.

PMID- 21847794
TI  - [Position Paper of the Youth Forum DGOU 2010 - part 2].
AB  - The aim of the "Youth Forum of the DGOU" during the Convention 2010 in Heidelberg
      was to place a statement concerning the professional politics in the field of
      Orthopaedic and Trauma Surgery. The Bologna Process realizes a standardization of
      the academic training within the European Union. For medicine this concept would
      raise the opportunity to opt out after three years with a bachelor degree
      applying for alternative occupations within the health care system. However,
      these alternative occupations are rarely defined and, in addition, the current
      structure of medical school in Germany provides the highest possible education
      for doctors in a direct and very well established way. Thus, reforming medical
      school in Germany into a Bachelor-master's system is an ambivalent approach,
      which considers a thorough reappraisal. There is currently no necessity for an
      speciality training in emergency medicine. The rapid and qualified treatment by
      the specific subspecialty provides a high standard of care for the patient. The
      high frequency exposure of the trauma and orthopaedic resident with emergency
      cases is an essential part of the current professional training.The "Junge Forum
      der DGOU" continues to understand the speciality training "Facharzt fur
      Orthopadie und Unfallchirurgie" as the basic module of the profession. After that
      it should be possible to continuing subspecialty training and obtaining
      "spezielle Unfallchirurgie" bzw "spezielle orthopadische Chirurgie". After that
      further subspecialty training should be encouraged.

PMID- 21847796
TI  - Regulating mRNA complexity in the mammalian brain.

PMID- 21847797
TI  - Abstracts of the IEA World Congress of Epidemiology. August 7-11, 2011.
      Edinburgh, Scotland, United Kingdom.

PMID- 21847798
TI  - Abstracts of Strategies for Engineered Negligible Senescence (SENS) Fifth
      Conference. August 31-September 4, 2011. Cambridge, United Kingdom.

PMID- 21847799
TI  - [COPD--too little, too much medication and dismantling].

PMID- 21847800
TI  - Utilizing Medicare claims data for real-time drug safety evaluations:is it
      feasible?
AB  - PURPOSE: The Centers for Medicare & Medicaid Services claims comprise an
      administrative database of beneficiary-specific clinical information. This study
      evaluates the impacts of (i) claim information updates (claims adjudication) and
      (ii) delay in claim processing (claims delay) on real-time evaluation of health
      service and drug safety signals using the Medicare database. METHODS: Using
      Medicare claims data accumulated through May 2009 on health services rendered in
      2006 and drugs dispensed in 2007, this study measures the frequency with which
      clinical information changes in the database as a result of (i) claims
      adjudication and (ii) claims delay. RESULTS: Over 85% of health services claims
      were processed within 8 weeks after the date of service, and 72% of drug claims
      were processed within 3 months after the dispense date. Clinical information
      changed for no more than 3% of unique claim groups in inpatient hospital,
      outpatient institutional, physician's office, and prescription drug Medicare
      claim settings. CONCLUSIONS: Claims delay is consistent across time and is
      minimal. Claims adjudication does not substantially impact the content of
      clinical information in the Medicare claims database. Therefore, the Medicare
      claims database provides consistent information regarding health services and
      prescription drugs in a manner that is prompt enough to facilitate medical
      product safety evaluations in real time.

PMID- 21847801
TI  - Abstracts of the First International Congress, Mycobacteria, a Challenge for the
      21st Century. September 24-27, 2008. Bogota, Columbia.

PMID- 21847802
TI  - Response to psychosocial treatment in poststroke depression is associated with
      serotonin transporter polymorphisms.
AB  - BACKGROUND AND PURPOSE: The Living Well With Stroke study has demonstrated
      effectiveness of a brief psychosocial treatment in reducing depressive symptoms
      after stroke. The purpose of this analysis was to determine whether key variables
      associated with prevalence of poststroke depression also predicted treatment
      response. METHODS: Response to a brief psychosocial/behavioral intervention for
      poststroke depression was measured with the Hamilton Rating Scale for Depression.
      Analysis of covariance models tested for interaction of potential predictor
      variables with treatment group on percent change in Hamilton Rating Scale for
      Depression from pre- to post-treatment as an outcome. RESULTS: Initial depression
      severity, hemispheric location, level of social support, age, gender, and
      antidepressant adherence did not interact with the treatment with respect to
      percent change in Hamilton Rating Scale for Depression when considered 1 at a
      time. Participants who carried 1 or 2 s-alleles at the 5-HTTLPR serotonin
      transporterpolymorphism or 1 or 2 9- or 12-repeats of the STin2 VNTR polymorphism
      had significantly better response to psychosocial treatment than those with no s
      alleles or no 9- or 12-repeats. CONCLUSIONS: Opposite to the effects of
      antidepressant drug treatment with selective serotonin reuptake inhibitors, the
      Living Well With Stroke psychotherapy intervention was most effective in 5-HTTLPR
      s-allele carriers and STin2VNTR 9- or 12-repeat carriers. CLINICAL TRIAL
      REGISTRATION: URL: www.clinicaltrials.gov/ct/show/NCT00194454?order_1. Unique
      identifier: NCT00194454.

PMID- 21847803
TI  - Abstracts of the British Society for Paediatric Dentistry Annual Scientific
      Meeting. September 13-16, 2011. Glasgow, Scotland, United Kingdom.

PMID- 21847804
TI  - Humanitarian response inadequate in Horn of Africa crisis.

PMID- 21847805
TI  - Laughing to longevity--the work of elder clowns.

PMID- 21847806
TI  - Enzymology and molecular biology of carbonyl metabolism. Proceedings of the 15th
      International Meeting on Enzymology and Molecular Biology of Carbonyl Metabolism.
      July 6-11, 2010. Lexington, Kentucky, USA.

PMID- 21847807
TI  - Proceedings of the 8th International Conference on Equine Exercise Physiology.
      November 7-12, 2010. Cape Town, South Africa.

PMID- 21847808
TI  - Proceedings of the 7th International Headache Seminar. May 26-28, 2011. Stresa,
      Italy.

PMID- 21847809
TI  - Proceedings from the ice hockey summit on concussion: a call to action.
AB  - OBJECTIVE: The objective of this proceeding is to integrate the concussion in
      sport literature and sport science research on safety in ice hockey to develop an
      action plan to reduce the risk, incidence,severity, and consequences of
      concussion in ice hockey. methods: A rationale paper outlining a collaborative
      action plan to address concussions in hockey was posted for review two months
      prior to the Ice Hockey Summit: Action on Concussion. Focused presentations
      devoted specifically to concussion in ice hockey were presented during the Summit
      and break out sessions were used to develop strategies to reduce concussion in
      the sport. This proceedings and a detailed scientific review (a matrix of
      solutions) were written to disseminate the evidence based information and
      resulting concussion reduction strategies. The manuscripts were reviewed by the
      authors, advisors and contributors to ensure that the opinions and
      recommendations reflect the current level of knowledge on concussion in hockey.
      RESULTS: Six components of a potential solution were articulated in the Rationale
      paper and became the topics for breakout groups that followed the professional,
      scientific lectures. Topics that formed the core of the action plan were: metrics
      and databases; recognizing,managing, and return to play; hockey equipment and ice
      arenas;prevention and education; rules and regulations; and expedient
      communication of the outcomes. The attendees in breakout sessions identified
      action items for each section. The most highly ranked action items were brought
      to a vote in the open assembly, using an Audience Response System (ARS). The
      strategic planning process was conducted to assess: Where are we at?; Where must
      we get to?; and What strategies are necessary to make progress on the prioritized
      action items? CONCLUSIONS: Three prioritized action items for each component of
      the solution and the percentage of the votes received are listed in the body of
      this proceeding.

PMID- 21847810
TI  - Psychophysiology of psychological disorders. Special issue dedicated to Walton T.
      Roth on the occasion of his 70th birthday.

PMID- 21847812
TI  - Society for the Quantitative Analyses of Behavior - choice, discounting, and the
      future value of quantitative analyses. Proceedings of the 33rd Annual Meeting of
      the Society for the Quantitative Analyses of Behavior. May 27-29, 2010. San
      Antonio, Texas, USA.

PMID- 21847811
TI  - Special issue on carbon and related nanomaterials, a Festschrift in memory of
      Peter Clay Eklund.

PMID- 21847813
TI  - Proceedings of the International Topical Meeting on Polonium and Radioactive Lead
      Isotopes. October 26-28, 2009. Seville, Spain.

PMID- 21847814
TI  - Responding toward the source of stimulation. Proceedings of an international
      conference to celebrate the work of J. Richard Simon.

PMID- 21847815
TI  - Proceedings of the Fourth International Conference on Applied Hair Science.
      October 5-6, 2010. Princeton, New Jersey, USA.

PMID- 21847816
TI  - Proceedings of the Eight International Symposium on Reproduction in Domestic
      Ruminants. September 3-7, 2010. Anchorage, Alaska, USA.

PMID- 21847817
TI  - [Lymph cell interstitial pneumonia].

PMID- 21847818
TI  - Abstracts of 37th European Symposium on Calcified Tissues. Glasgow, Scotland,
      United Kingdom. June 26-30, 2010.

PMID- 21847819
TI  - Visual mismatch response evoked by a perceptually indistinguishable oddball.
AB  - Mismatch field (MMF) is an early magnetoencephalographic response evoked by
      deviant stimuli within a sequence of standard stimuli. Although auditory MMF is
      reported to be an automatic response, the automaticity of visual MMF has not been
      clearly demonstrated, partly because of the difficulty in designing an ignore
      condition. Our modified oddball paradigm had a masking stimulus inserted between
      briefly presented standard and deviant stimuli (vertical gratings with different
      spatial frequencies). Perceptual discrimination between masked standard and
      deviant stimuli was difficult, but the early magnetoencephalographic response for
      the deviant was significantly larger than that for the standard, when the former
      had a higher spatial frequency than the latter. Our findings strongly support the
      hypothesis that visual MMF is evoked automatically.

PMID- 21847820
TI  - Retraction notice to "Prophylactic use of pentoxifylline on inflammation in
      elderly cardiac surgery patients".

PMID- 21847821
TI  - Retraction notice to "Influence of prolonged cardiopulmonary bypass times on
      splanchnic perfusion and markers of splanchnic organ function".

PMID- 21847822
TI  - Case study. Too much to ask? Commentary.

PMID- 21847823
TI  - [Possibilities of endoscopic stenting in the treatment of gastrointestinal and
      biliary system diseases].
AB  - The efficacy of endoscopic treatment of patients for stenosis and stricture of
      the gut organs and biliary ducts, using stents, was analyzed. In 48 patients,
      suffering tumoral and inflammatory diseases of the gut, biliary ducts and
      respiratory ways, selfexpanding metal stents, produced by firm Sooho M.I.-Tech.
      Co, Diagmed (Southern Korea), were introduced to reduce the severity of
      dysphagia, jaundice and the intestinal passability restoration. This had promoted
      the passability disorders elimination and the organs wall integrity restoration.
      In 16.6% of patients the immediate postinterventional period was complicated by
      occurrence of a short-term pain syndrome. In 6.2% of patients in 5-6 months the
      additional stenting intervention "stent into the stent" was performed for the
      stent restenosing. In 7-8 months the recurrent dysphagia have had occurred in
      4.2% of patients. Endoscopic treatment of stenosis and stricture of the gut
      organs and biliary ducts, using self-expanding metal stents, is an effective,
      safe and secure procedure.

PMID- 21847824
TI  - [Fragment of the all-Ukrainian investigation of the microflora sensitivity to
      antibacterial preparations in patients with intra-abdominal surgical infection].
AB  - All-Ukrainian investigation of microflora sensitivity to antibacterial
      preparations in patients with intraabdominal infection (IAI) have included
      studying of microbial landscape of the abdominal cavity content in IAI, and the
      causing agents sensitivity to main antibacterial preparations was determined,
      including those, manufactured by corporation "Arterium" (Ukraine).

PMID- 21847825
TI  - [The method of surgical correction of the endoprosthesis ptosis after performance
      of subglandular enlarging mammoplasty].
AB  - The method of reendoprosthesis of mammary glands after performance of
      subglandular enlarging mammoplasty for the glands form correction, the implants
      ptosis occurrence in postoperative period prophylaxis, reduction of possibility
      of the capsular contracture occurrence, as well as reduction of the implants
      "visualization" and palpation rate, especially in patients-women lacking covering
      tissues volume, was adduced. In 2005-2010 yrs in the Centre there were performed
      18 operations of the mammary glands reendoprosthesis after subglandular enlarging
      mammoplasty using the method proposed. Maximal duration of follow-up have
      constituted five years. In 17 patients-women the result was estimated as an
      excellent and in 1--as good. Application of this method guarantees the
      foreseeable and stable late results achievement, as well as satisfaction of
      patients and surgeons. The perspective of further development of scientific
      investigation assumes studying of late results concerning application of the
      method proposed.

PMID- 21847826
TI  - ["Ecology and health"--priority research trend in Kazakhstan].
AB  - Research works covering longevity, longer life expectancy and influence of
      ecologic conditions on health are topical among important strategic trends. The
      authors presented contemporary project of research concerning influence of
      ecologic factors on health of urban inhabitants. The project is carried out by
      National Centre of Labour Hygiene and Occupational Diseases since 2010, and the
      results will define cause-effect relationship of possible environmental hazards,
      disclose basic pathogenetic mechanisms of ecologically dependent diseases with
      evaluation of induced mutagenesis and metabolic disorders level.

PMID- 21847827
TI  - [What is pathophysiology nowadays? The reflections of the participants of ISP
      2010 Congress in Montreal].
AB  - The main tendencies in the development of Pathophysiology as a science and
      teaching discipline are analyzed in the light of last 6th ISP-2010 Congress. The
      witnesses for the growing integration between Pathophysiology and other basic
      medical sciences are given, along with the preserved specifics of the
      pathophysiological knowledge on the etiology, pathogenesis and models of the
      diseases and pathological processes. The current role and place of
      Pathophysiology as Systemic Pathobiology within the structure of medical sciences
      are discussed.

PMID- 21847829
TI  - Governing sex workers in Timor Leste.
AB  - This paper argues that international security forces in Timor Leste depend upon
      civilian partners in HIV/AIDs "knowledge networks" to monitor prostitutes'
      disease status. These networks produce mobile expertise, techniques of government
      and forms of personhood that facilitate international government of distant
      populations without overt coercion. HIV/AIDs experts promote techniques of peer
      education, empowerment and community mobilisation to construct women who sell sex
      as health conscious sex workers. Such techniques make impoverished women
      responsible for their disease status, obscuring the political and economic
      contexts that produced that status. In the militarised context of Timor Leste,
      knowledge of the sexual conduct of sub-populations labelled high risk circulates
      among global HIV/AIDs knowledge networks, confirming their expert status while
      obscuring the sexual harm produced by military intervention. HIV/AIDs knowledge
      networks have recently begun to build Timorese sex worker organisations by
      contracting an Australian sex worker NGO to train a Timorese NGO tasked with
      building sex worker identity and community. Such efforts fail to address the
      needs and priorities of the women supposedly empowered. The paper engages
      theories of global knowledge networks, mobile technologies of government, and
      governmentality to analyse policy documents, reports, programmes, official
      statements, speeches, and journalistic accounts regarding prostitution in Timor
      Leste.

PMID- 21847830
TI  - Composite farming systems in an era of change: Nagaland, Northeast India.
AB  - Composite farming systems, first clearly identified by Rambo, are those in which
      radically different technologies are found together in a single farming complex.
      Data from diaries kept by groups of farming families in two Angami Naga villages
      in northeast India, Khonoma and smaller Tsiesema, detailing inputs into and
      outputs from wet-rice terraces and jhum (swidden) fields in the years 2000 and
      2001, are presented and discussed to detail the workings of related but different
      composite systems. The 2000-2001 survey caught an important set of changes in
      midstream. Although returns to labour from the first-year jhums were much higher
      than those from the wet-rice terraces in 2000-2001, jhums were declining in
      significance as a growing non-farm economy joined the production of cool-climate
      vegetables and a spice crop for the Indian market as principal sources of
      livelihood. This story is told in the light of recent writing on the demise of
      swidden in the larger Southeast Asian region, and it is suggested that greater
      attention be paid to the composite systems, which are not uncommon in this
      region. This might help diversify what has perhaps been an oversimplified
      discussion.

PMID- 21847832
TI  - Parents and children in Second World War Germany: an inter-generational
      perspective on wartime separation.
AB  - This article discusses how the relationship between parents and their children
      were affected by the second world war in Germany. With fathers away from home for
      often as long as a decade, many children grew up without a father being
      physically present. The current historiography suggests that wartime separation
      caused a crisis in the family. But did the prolonged periods of time apart and
      the separate experiences of husbands at the Front and wives and children at home
      really destabilize family relationships? This article questions such a picture of
      families in ruin. It argues that family relationships were far more resilient in
      the face of wartime separation than has previously been credited. Indeed, it
      reveals the importance of children in keeping mothers and fathers focused on
      getting through the war. It further contends that, even from afar, fathers
      continued to play an important role in their children's lives. And this in turn
      revises our understanding of the situation facing reuniting families.

PMID- 21847831
TI  - Exploring Thailand's mortality transition with the aid of life tables.
AB  - The project Thai Health-Risk Transition: A National Cohort Study seeks to better
      understand the health implications of modernisation and globalisation forces
      impacting on Thailand. As part of its "look-back" component this paper seeks,
      using available life tables, to document the country's post-war mortality
      transition. The onset of transition through mass campaigns of the late 1940s and
      1950s is first discussed before attention turns to the life tables. They are
      predictably far from flawless, but careful analysis does permit trends that have
      seen around 30 years added to life expectancy to be traced, and age patterns of
      improved survivorship and their relation to initiatives to improve health to be
      examined. The broad benefits generated by mass campaigns, ongoing improvements in
      infant and early childhood mortality, and a phased impact of the expansion of
      primary health care in rural areas on adult survival prospects after the mid
      1970s are demonstrated. The paper also investigates the consequences for
      mortality of a motorcycle-focused rapid increase in road fatalities in the late
      1980s and early 1990s and the HIV/AIDS epidemic that developed after 1984.

PMID- 21847834
TI  - Expanding the Kachemak: surplus production and the development of multi-season
      storage in Alaska's Kodiak Archipelago.
AB  - Surplus production is a hallmark of Alaska's prehistoric coastal societies. Over
      the millennia, foragers procured greater quantities of resources with increasing
      efficiency, developing economies dependent upon storage and institutionalized
      exchange. In the central Gulf of Alaska, notable evidence of surplus production
      comes from the late phase of the Kachemak tradition. Since de Laguna's pioneering
      studies, archaeologists have noted that intensified fishing, storage, and
      exchange typify this tradition. However, few have investigated the roots of these
      behaviors. When, how, and why did foragers begin producing well beyond immediate
      needs? This paper explores archaeological evidence for surplus production in the
      Kodiak Archipelago, focusing on patterns in land use, technology, and exchange
      preserved in Ocean Bay II and Early Kachemak assemblages from the Chiniak Bay
      region. It suggests that surplus production for the purposes of seasonal food
      storage began in the Early Kachemak, and accelerated in the Late Kachemak as
      population levels climbed.

PMID- 21847836
TI  - Factors in the adaptation of reindeer herders to caribou on the Seward Peninsula,
      Alaska.
AB  - Over the last century, reindeer herding has provided a major economic base in
      Eskimo villages on the Seward Peninsula, Alaska, and has come to represent an
      important dimension of Native cultural identity. As a result of the current
      population explosion of caribou from the Western Arctic Caribou Herd, along with
      a shift in the herd's migratory patterns, reindeer ranges that were free of
      caribou for generations are now being flooded by tens of thousands. Reindeer join
      these migrating caribou and leave their ranges. As individual herders lose
      reindeer to the caribou, the impact is felt at the individual, community, and
      regional level. This paper describes some of the factors that influence modern
      day Eskimo herders' ability to cope with this devastating situation. The herders'
      descriptions of the crisis lead us to a larger and more comprehensive picture of
      how they understand and respond to the environmental conditions, technology, and
      economic conditions that they face.

PMID- 21847835
TI  - A Foucaultian approach to menstrual practices in the Dehcho Region, Northwest
      Territories, Canada.
AB  - In this paper, I explore the benefits of using a Foucaultian approach to examine
      research questions related to Dene women, menstrual traditions, and physical
      practices (the term physical practices is here used to encompass the contested
      terms sport, recreation, traditional games, and physical activity) in the Dehcho
      region of the Northwest Territories, Canada. While it is clear that Indigenous
      research frameworks have been marginalized in past research projects, this paper
      argues that the current approach of using almost exclusively Indigenous
      frameworks when conducting research with Indigenous communities has several
      drawbacks and relies on some troubling assumptions. After outlining the strengths
      of a Foucaultian approach, examples derived from fieldwork in the Dehcho region
      are used to illustrate the ways in which a Foucaultian approach can be
      operationalized, while also demonstrating the ways in which such an approach to
      research can complement Indigenous research frameworks and agendas.

PMID- 21847837
TI  - Housing policy, aging, and life course construction in a Canadian Inuit
      community.
AB  - The provisioning and administration of social housing has been a continuous
      problem in the Canadian North since the 1960s, when the Canadian government began
      taking an active role in the welfare of Inuit. Some of these problems are quite
      basic and include high costs for construction and maintenance of units. An
      examination of the development and evolution of Canadian housing policy in the
      North demonstrates that changes to the administration of social housing programs
      and, since the mid-1980s, development of formal privatization schemes have
      steadily shifted housing costs onto local residents. These shifting costs,
      however, are borne unequally, with Inuit born and raised in the context of
      permanent communities (the Settlement Generation) facing the greatest burdens.

PMID- 21847838
TI  - Wage labor, housing policy, and the nucleation of Inuit households.
AB  - Public policy practices in the Canadian North, particularly those connected to
      housing and employment, are encouraging a reorganization of Inuit social
      organization to more closely resemble the insular and independent nuclear family
      household idealized by Eurocanadians. This has wide-ranging implications for the
      social stability of northern communities without sufficient employment
      opportunities. The paper examines the symbolic and structural effects of housing
      policies and employment on culturally valued social practices such as sharing in
      Holman, a community in the Inuvialuit Settlement Region of the Northwest
      Territories of Canada.

PMID- 21847839
TI  - Norse Greenland settlement: reflections on climate change, trade, and the
      contrasting fates of human settlements in the North Atlantic Islands.
AB  - Changing economies and patterns of trade, rather than climatic deterioration,
      could have critically marginalized the Norse Greenland settlements and
      effectively sealed their fate. Counter-intuitively, the end of Norse Greenland
      might not be symptomatic of a failure to adapt to environmental change, but a
      consequence of successful wider economic developments of Norse communities across
      North Atlantic. Data from Greenland, the Faroe Islands, and medieval Iceland is
      used to explore the interplay of Norse society with climate, environment,
      settlement, and other circumstances. Long term increases in vulnerability caused
      by economic change and cumulative climate changes sparked a cascading collapse of
      integrated interdependent settlement systems, bringing the end of Norse
      Greenland.

PMID- 21847840
TI  - Close relatives and outsiders: village people in the city of Yakutsk, Siberia.
AB  - The paper presents a snapshot of the city-village connections in the city of
      Yakutsk and an anthropological account of the dynamics of the relationship
      between the city and villages around it. Demographic changes that started in the
      1980s, prompted by a decline in agriculture, initiated an exodus of the rural
      population from the countryside into the city of Yakutsk. This paper explores the
      migration dynamics of the rural population to the city. Two conflicting aspects
      of the relationship between the city and village are the focus of this paper:
      treating village people as close kin and as outsiders. I examine the image of
      ulusnik [a villager] and consider rationales behind the stigma attached to it and
      a social role of the Other which is imposed on the people from the countryside.

PMID- 21847841
TI  - Comparing Norse animal husbandry practices: paleoethnobotanical analyses from
      Iceland and Greenland.
AB  - The popular view of the Norse settlement across the North Atlantic describes
      colonies with similar subsistence practices being established from the Faroe
      Islands in the west to L'Anse aux Meadows in the east. The importance of plant
      resources to the Norse animal husbandry strategies implemented by settlers upon
      arrival are not well established, nor are the changes these strategies underwent,
      eventually resulting in different cultural solutions to varying environmental and
      social factors. This paper compares archaeobotanical samples from two Icelandic
      archaeological sites, Svalbard and Gjogur, and one Greenlandic site, Garden Under
      Sandet (GUS). Results of this comparison suggest that heathland shrubs were an
      important fodder resource for caprines in both Iceland and Greenland while
      apophytes ("weedy taxa") were part of the cattle fodder in Greenland. Further,
      the results indicate that mucking out of cattle barns to provide fertilizer was
      likely practiced at the GUS site in the Western Norse settlement of Greenland.

PMID- 21847842
TI  - A tundra of sickness: the uneasy relationship between toxic waste, TEK, and
      cultural survival.
AB  - In 1992 an abandoned federal radioactive waste dump was discovered in Arctic
      Alaska. The discovery of this site, a byproduct of the Atomic Energy Commission
      program known as Project Chariot, sent shockwaves throughout Inupiaq communities
      and ignited a heated controversy over the health effects of subsisting on a
      "tundra of sickness." Drawing on thirty months of ethnographic research in Arctic
      Alaska, this paper explores a host of environmental, social, and moral
      uncertainties sparked by toxic waste. Anthropological claims regarding the extent
      to which "traditional ecological knowledge" will empower local communities and
      foster self-determination are challenged. Ultimately the paper argues that TEK
      has been conceived in such restrictive terms that it misrepresents the dynamic,
      emerging, and at times contradictory responses to toxic waste in the Arctic
      today. Moreover, there is dire need for a more materialist, as opposed to
      discourse-based, approach that acknowledges the very real threat of toxic waste
      to physical, and therefore, cultural reproduction.

PMID- 21847843
TI  - The St. Lawrence Island famine and epidemic, 1878-80: a Yupik narrative in
      cultural and historical context.
AB  - A collaborative study of the Smithsonian Institution's ethnology collections has
      inspired the narration of Alaska Native oral traditions, including Yupik Elder
      Estelle Oozevaseuk's re-telling (in 2001) of the story of Kukulek village and the
      St. Lawrence Island famine and epidemic of 1878-80. The loss of at least 1,000
      lives and all but two of the island's villages was a devastating event that is
      well documented in historical sources and archaeology, as well as multiple Yupik
      accounts. Yupiget have transmitted memories of extreme weather, bad hunting
      conditions, and a wave of fatal contagion that swept the island. The Kukulek
      narrative, with origins traceable to the late nineteenth century, provides a
      spiritual perspective on the disaster's underlying cause, found in the Kukulek
      people's disrespect toward the animal beings that sustained them. This paper
      explores the cultural and historical contexts of this narrative, and contrasts it
      with Western perspectives.

PMID- 21847844
TI  - Elder knowledge and sustainable livelihoods in post-Soviet Russia: finding
      dialogue across the generations.
AB  - Russia's indigenous peoples have been struggling with economic, environmental,
      and socio-cultural dislocation since the fall of the Soviet Union in 1991. In
      northern rural areas, the end of the Soviet Union most often meant the end of
      agro-industrial state farm operations that employed and fed surrounding rural
      populations. Most communities adapted to this loss by reinstating some form of
      pre-Soviet household-level food production based on hunting, fishing, and/or
      herding. However, mass media, globalization, and modernity challenge the
      intergenerational knowledge exchange that grounds subsistence practices. Parts of
      the circumpolar north have been relatively successful in valuing and integrating
      elder knowledge within their communities. This has not been the case in Russia.
      This article presents results of an elder knowledge project in northeast Siberia,
      Russia that shows how rural communities can both document and use elder knowledge
      to bolster local definitions of sustainability and, at the same time, initiate
      new modes of communication between village youth and elders.

PMID- 21847845
TI  - Stigmatized ethnicity, public health, and globalization.
AB  - The prejudicial linking of infection with ethnic minority status has a long
      established history, but in some ways this association may have intensified under
      the contemporary circumstances of the "new public health" and globalization. This
      study analyzes this conflation of ethnicity and disease victimization by
      considering the stigmatization process that occurred during the 2003 outbreak of
      Severe Acute Respiratory Syndrome (SARS) in Toronto. The attribution of stigma
      during the SARS outbreak occurred in multiple and overlapping ways informed by:
      (i) the depiction of images of individuals donning respiratory masks; (ii)
      employment status in the health sector; and (iii) Asian-Canadian and Chinese
      Canadian ethnicity. In turn, stigmatization during the SARS crisis facilitated a
      moral panic of sorts in which racism at a cultural level was expressed and
      rationalized on the basis of a rhetoric of the new public health and anti
      globalization sentiments. With the former, an emphasis on individualized self
      protection, in the health sense, justified the generalized avoidance of those
      stigmatized. In relation to the latter, in the post-9/11 era, avoidance of the
      stigmatized other was legitimized on the basis of perceiving the SARS threat as a
      consequence of the mixing of different people predicated by economic and cultural
      globalization.

PMID- 21847846
TI  - Reading baby books: medicine, marketing, money and the lives of American infants.
AB  - This article examines American baby books from the late nineteenth through the
      twentieth century. Baby books are ephemeral publications-formatted with one or
      more printed pages for recording developmental, health, and social information
      about infants and often including personal observations, artifacts such as
      photographs or palm prints, medical and other prescriptive advice, and
      advertisements. For historians they serve as records of the changing social and
      cultural worlds of infancy, offering insights into the interplay of childrearing
      practices and larger social movements.Baby books are a significant historical
      source both challenging and supporting current historiography, and they
      illustrate how medical, market and cultural forces shaped the ways babies were
      cared for and in turn how their won behavior shaped family lives. A typology of
      baby books includes the lavishly illustrated keepsake books of the late
      nineteenth century, commercial and public health books of the twentieth century,
      and on-line records of the present day. Themes that emerge over time include
      those of scientific medicine and infant psychology, religion and consumerism. The
      article relies on secondary literature and on archival sources including the
      collections of the UCLA Louise M. Darling Biomedical Library as well as privately
      held baby books.

PMID- 21847847
TI  - Some utilitarian influences in Freud's early writings.
AB  - The author argues that (1) the utilitarian ideas of Jeremy Bentham and John
      Stuart Mill were an important source for Freud's early metapsychology and (2) the
      two theories are radically different in many aspects. The facts that link Freud
      with the British utilitarian school are described in the first part. These
      include Freud's translation of three of Mill's essays, a course Freud took on
      utilitarianism as a student and a book written by Mill which Freud cited and held
      in his library. By stripping Freud's language of its biological connotations the
      author claims in the second part that utilitarianism ideas are ubiquitous in
      Freud's early thought especially in his "pleasure principle" and in the
      hedonistic side of the human psyche. The third part describes how Freudian theory
      breaks with utilitarianism along three lines: the quality of pleasure, conflict
      and irrationality. These breaks are demonstrated through concepts such as the
      quantity-quality dilemma, constancy principle, repression, conflict and
      hallucination. Although there is a strong basic philosophical affinity (certainly
      with regard to human motivation) between Freudian thought and utilitarianism the
      theories should not be compared on the same level.

PMID- 21847848
TI  - Fathers and sons: Freud's discovery of the Oedipus complex.
AB  - Freud's path to the Oedipus complex reveals conceptual inconsistencies. These
      uncertainties concern fathers, brothers and sons, and the place of the oedipal
      triad within the family romance. Freud's uncovering of the Oedipus complex
      emerged, in large part, from his self-analysis of his childhood years in
      Freiberg. Freud's father was 20 years older than his third wife, and had two
      adult sons, all of whom lived in Freiberg. In 1897, when Freud announces the
      Oedipus complex, he stresses his love of his mother and jealousy of his father.
      Yet in 1924 Freud wrote that his adult brother, Philipp, had taken his father's
      place as the child's rival. The oedipal complex alters if there are four players
      rather than three. Freud's concept of an oedipal triangle does not adequately
      explain the psychological dynamics of his childhood. Fuller conceptual clarity
      would occur if the dynamics of the Oedipus complex were placed within the family
      context in which it unfolds.

PMID- 21847849
TI  - Key design elements of shared-savings payment arrangements.
AB  - Shared savings is a payment strategy that offers incentives for providers to
      reduce health care spending for a defined patient population by offering them a
      percentage of net savings realized as a result of their efforts. The concept has
      attracted great interest, in part fueled by Affordable Care Act provisions that
      create accountable care organizations and by the movement among medical home
      pilots to make payment methodologies more performance-based. In this issue brief,
      the authors interviewed payer and provider organizations and state agencies
      involved in shared-savings arrangements about their diverse approaches, including
      the populations and services covered, the assignment of providers, the use of
      risk adjustment, and the way savings are calculated and distributed. The authors
      identified issues payers and providers must resolve going forward, including
      determining whether savings were achieved, equipping providers with necessary
      tools and technical advice, agreeing upon standard performance measures, and
      refining the model over time.

PMID- 21847850
TI  - [Orthognathic surgery. Introduction].

PMID- 21847851
TI  - The e-learning site.

PMID- 21847852
TI  - Transforming at-one-ment: Spielrein, Jung, Bion.
AB  - To remedy the relative neglect of the contribution of Sabina Spielrein to
      psychoanalysis this article details her early life, psychiatric hospitalization,
      analysis by Jung, love affair with him, extracts from her diary, correspondence
      with Jung and Freud, and published writing. Together this material highlights
      Spielrein's pioneering insights regarding the involvement of what Bion
      subsequently called "at-one-ment" in (a) the transformations effected by the
      transference-countertransference of patient and analyst in analysis, (b) art, (c)
      symbolism as universalizing inspiration or defence, (d) the death instinct, (e)
      the subconscious as semiotic mediator between what is conscious and unconscious,
      and (f) children's early language acquisition.

PMID- 21847853
TI  - Towards a psychoanalytic understanding of Fascism and anti-Semitism: perceptions
      from the 1940s.
AB  - After selecting five representative European psychoanalytic thinkers, all of whom
      emigrated to the United States, this essay surveys their earliest perceptions and
      interpretations of the historical and psychological roots of Fascism, with
      particular emphasis on anti-Semitism. My samples almost all derive from the
      period before, during, and immediately after World War II. In examining the
      writings of Otto Fenichel, Ernst Simmel, Erik Homburger Erikson, Rudolf
      Loewenstein and Bruno Bettelheim, it discusses the various environmental and
      psychological dimensions of their understandings of racial prejudice. The paper
      argues that each thinker attempted to integrate historical, sociological,
      cultural and clinical factors into their psychodynamic formulations about the
      individual and group mind of the Fascist anti-Semite. This generation of
      psychoanalysts explained Fascist anti-Semitism by exploring the mechanisms of
      projection, the process of massive splitting mechanisms of the group mind,
      fantasies of delinquent adolescent aggrandizement in Hitler, sado-masochistic and
      perverse oedipal dynamics, and a macabre identification with the torturers on the
      part of Jewish inmates in the concentration camps, that obliterated the
      individual's sense of autonomy and capacity to respond morally. The paper points
      out the pronounced ambivalence of this generation of Jewish analysts and
      intellectuals toward their own Jewish backgrounds and sense of themselves as
      Jews. It also argues that this generation muted its left-wing and socialist
      political tendencies once they arrived in America, taking a turn against
      politics. It suggests that some of the features of this Jewish ambivalence can be
      seen in the exploration of a so-called "Jewish psychology," itself a disguised
      form of racism, a derivative of projection, which may have had rather negative
      and authoritarian consequences for the psychoanalytic movement in America.

PMID- 21847854
TI  - Potential role of recombinant erythropoietin and intravenous iron preparations in
      target vessel re-stenosis following coronary stint insertions in hemodialysis
      patients.

PMID- 21847855
TI  - Kounis syndrome following food-dependent exercise-induced anaphylaxis.

PMID- 21847856
TI  - Salvation of the diabetic foot: still a quest for the Holy Grail?

PMID- 21847857
TI  - In a position to help.

PMID- 21847858
TI  - Regulator advises staff to retain evidence of continued learning.

PMID- 21847860
TI  - RCN plans 'vigorous' challenge to proposed pension changes.

PMID- 21847859
TI  - Responsibilities of nurse leaders will be increased, says NMC chief.

PMID- 21847861
TI  - Practice nurses express greatest pessimism about care provision.

PMID- 21847862
TI  - Trusts line up to attack national terms in drive to make savings.

PMID- 21847863
TI  - Counting the cost of failure.

PMID- 21847864
TI  - Wasted opportunities.
AB  - Teenage misuse of alcohol is rarely out of the headlines. According to a new
      report, those young people who end up in A&E as a result of drinking do not
      receive appropriate interventions.

PMID- 21847865
TI  - The quiet heroes.
AB  - When a 6.3 magnitude earthquake struck Christchurch, New Zealand, in February,
      Mary Chiarella discovered how 'collegial generosity' among nurses works.

PMID- 21847866
TI  - Improving the health care of women living with domestic abuse.
AB  - AIM: To explore the healthcare experiences of women living with domestic abuse,
      specifically in relation to the primary care setting. METHOD: A qualitative study
      was undertaken in Scotland, comprising semi-structured interviews with 17 women
      who had experienced domestic abuse. Data were analysed using a thematic
      framework. FINDINGS: Three themes were linked to women's healthcare experiences:
      systems-based, interpersonal and psychological issues. Poor systems of
      communication sometimes fail abused women, and low self-esteem and fear of
      stigmatisation make it difficult for women to discuss abuse. CONCLUSION: Nurses
      in primary care settings can do much to support women who have experienced
      domestic abuse. Understanding the systems-based, interpersonal and psychological
      factors that influence women's healthcare experiences may be a vital part of this
      process.

PMID- 21847867
TI  - An evaluation of sharp safety blood evacuation devices.
AB  - This article describes an evaluation of three sharp safety blood evacuation
      devices in seven Welsh NHS boards and the Welsh Blood Service. Products consisted
      of two phlebotomy needles possessing safety shields and one phlebotomy device
      with wings, tubing and a retractable needle. The device companies provided the
      devices and appropriate training. Participating healthcare workers used the
      safety device instead of the conventional device to sample blood during the
      evaluation period and each type of device was evaluated in random order.
      Participants filled in a questionnaire for each type of device and then a further
      questionnaire comparing the two shielded evacuation needles with each other
      Results showed that responses to all three products were fairly positive,
      although each device was not liked by everyone who used it. When the two shielded
      evacuation devices were compared with each other, most users preferred the device
      with the shield positioned directly above the needle to the device with the
      shield at the side. However, in laboratory tests, the preferred device produced
      more fluid splatter than the other shielded device on activation.

PMID- 21847869
TI  - Undernutrition.

PMID- 21847868
TI  - The psychosocial effect of epilepsy on adolescents and young adults.
AB  - Adolescence is a time of rapid physical, psychological and social development.
      For young people with epilepsy, the normal needs and concerns associated with
      being an adolescent are complicated by the demands of a condition that can place
      additional limits on lifestyle and independence. It is essential for healthcare
      professionals to consider the effect of epilepsy on the lives of young adults and
      to recognise the specific needs of this patient group. This article provides an
      overview of the psychosocial effect of epilepsy on adolescents and makes
      recommendations for nursing practice.

PMID- 21847870
TI  - All in it together.

PMID- 21847871
TI  - Management: more than child's play.

PMID- 21847872
TI  - Learning global trends.

PMID- 21847873
TI  - Symposium on training and development in the health and human services sector.

PMID- 21847874
TI  - 21st century community learning centers--improving the academic performance of at
      risk students: a Bronx tale.
AB  - The authors of this article report on an intervention designed to improve the
      academic component of an extended after-school program. The agency involved in
      this intervention was a non-profit community action group (CAG) agency whose
      mission is to improve the socio-economic well-being of the residents of Upper
      Manhattan, the Bronx, and New York City. The agency has a staff of 200 that serve
      high school students. The intervention program was designed to (1) improve the
      working relationship between teachers, families, and students in the after-school
      program, (2) develop new and innovative ways to improve the academic curricula of
      the after-school program, and (3) provide continuous education to stakeholders to
      the after-school program. Improvements in student performance relating to
      attendance, academic work, discipline and social behaviors were reported. The
      intervention reported in this article has the potential of supporting learning
      and developmental outcomes over time.

PMID- 21847875
TI  - Healthcare managers' perceptions of professional development and organizational
      support.
AB  - PURPOSE: This article explores the participation of healthcare managers in
      professional development (PD) activities, the reasons for seeking PD and the
      perceived support of their organizations in terms of reward and recognition.
      METHODOLOGY: An exploratory survey was emailed to current and past members of
      three professional associations who share similar missions "to provide
      educational and networking opportunities" for their members in the southern
      region of Florida. FINDINGS: Findings suggest that healthcare managers and
      healthcare organizations both support and value personal and professional
      development. Certification by professional organizations appears to be a key
      credential for upward mobility. RESEARCH LIMITATIONS: This study serves as an
      initial attempt to account for the factors that explain differences in pursuing
      professional development activities. Given the exploratory nature of the study
      and low response rates, the findings provide direction for further research
      rather than conclusive judgments. PRACTICAL IMPLICATIONS: Continuous learning by
      managers and organizations should allow the healthcare industry to position
      itself for future challenges. ORIGINALITY: Across all settings, positions, age
      groups, and perceived organizational support, individuals seek professional
      certification suggesting recognition of the professional value associated with
      these certifications. The value attributed to certification and PD by healthcare
      managers is further demonstrated by our finding that individuals engage in these
      activities even in the absence of employer reimbursement.

PMID- 21847876
TI  - Adoption of an algorithm and client pathway for the aged and disabled: training
      implications for the health and human service sectors.
AB  - OBJECTIVES: This paper reports on a state agency's training activities undertaken
      to totally redesign a long-term-care (LTC) delivery system as part of the
      national Aging and Disability Resource Center (ADRC) initiative. METHOD: Through
      the development of an ADRC algorithm and the implementation of a corresponding
      client pathway, NJ DACS, a division of aging, aligned 14 separate core functions
      necessary for lifespan services. A Training Academy facilitated the adoption of
      five new health service delivery products and processes by state and county
      health and human services personnel. RESULTS: Intensive training activities
      resulted in the algorithm and client pathway framework being successfully
      disseminated in all 21 counties within a short timeframe. Barriers to training
      were reduced and acceptance of new protocols and processes were facilitated
      leading to rapid adoption. Implications for training of health and human service
      personnel are presented. Full adoption of the complete ADRC model across the
      state was directly linked to agency software integration. CONCLUSIONS: Promoting
      standardized service delivery for the aging population through the use of an
      algorithm and parallel client pathway is feasible as a training model for health
      care service delivery.

PMID- 21847877
TI  - Human capital management in government: replacing government retirees.
AB  - Faced with high levels of senior civil servant retirement in the coming years and
      limited by civil service requirements, government organizations often struggle to
      maintain the knowledge base of previous processes and results while promoting
      people who are truly interested in being leaders in an agency. Upcoming
      generations of public sector workers do not share the same motivation and
      workplace characteristics of current exiting civil servants, further complicating
      smooth transitions of leadership. Government personnel systems for the most part
      are inflexible and slow to hire, and retention methods for workers do not
      encourage succession planning. Against this backdrop, a five-phased human capital
      management system, using some of the best practices found in both public and
      private sector organizations, is proposed as a solution for replacing government
      retirees with workers who are prepared for their leadership and management roles.

PMID- 21847878
TI  - Health services utilization, satisfaction, and attachment to a regular source of
      care among participants in an urban health provider alliance.
AB  - This study examines the effect of a provider alliance on service utilization,
      satisfaction , self efficacy, and attachment to a regular source of care for
      participating low income urban children and their families. The use of Physician
      Assistants and community health workers to expand community outreach, primary
      care services, pediatric sub-specialty care, and service coordination within and
      between care settings improved health services utilization, satisfaction with
      health services, parental self efficacy in navigating the health care system for
      their children, and service convenience for an at-risk population. Also, the use
      of Physician Assistants to provide pediatric sub-specialty services did not have
      a negative effect on parental satisfaction with a child's care. Parents were
      slightly more satisfied with services received from a Physician Assistant in
      comparison with the physician sub- specialists in cardiology and nephrology
      clinics.

PMID- 21847879
TI  - Protecting scientific integrity: the commercial speech doctrine applied to
      industry publications.

PMID- 21847880
TI  - Off-label drug use and promotion: balancing public health goals and commercial
      speech.

PMID- 21847881
TI  - Commercial speech and off-label drug uses: what role for wide acceptance, general
      recognition and research incentives?
AB  - This article provides an overview of how the constitutional protections for
      commercial speech affect the Food and Drug Administration's (FDA) regulation of
      drugs, and the emerging issues about the scope of these protections. A federal
      district court has already found that commercial speech allows manufacturers to
      distribute reprints of medical articles about a new off-label use of a drug as
      long as it contains disclosures to prevent deception and to inform readers about
      the lack of FDA review. This paper summarizes the current agency guidance that
      accepts the manufacturer's distribution of reprints with disclosures. Allergan,
      the maker of Botox, recently maintained in a lawsuit that the First Amendment
      permits drug companies to provide "truthful information" to doctors about "widely
      accepted" off-label uses of a drug. While the case was settled as part of a fraud
      and abuse case on other grounds, extending constitutional protections generally
      to "widely accepted" uses is not warranted, especially if it covers the use of a
      drug for a new purpose that needs more proof of efficacy, and that can involve
      substantial risks. A health law academic pointed out in an article examining a
      fraud and abuse case that off-label use of drugs is common, and that
      practitioners may lack adequate dosage information about the off-label uses. Drug
      companies may obtain approval of a drug for a narrow use, such as for a specific
      type of pain, but practitioners use the drug for similar uses based on their
      experience. The writer maintained that a controlled study may not be necessary to
      establish efficacy for an expanded use of a drug for pain. Even if this is the
      case, as discussed below in this paper, added safety risks may exist if the
      expansion covers a longer period of time and use by a wider number of patients.
      The protections for commercial speech should not be extended to allow
      manufacturers to distribute information about practitioner use with a disclosure
      about the lack of FDA approval. Distributions of information about unapproved
      uses should not be acceptable unless experts consider the expanded use to be
      generally recognized as safe and effective based on adequate studies. The last
      part of this paper considers the need to develop better research incentives to
      encourage more testing and post-market risk surveillance by drug makers on off
      label uses of their drugs. Violations of the Federal Food Drug and Cosmetic Act
      (FFDCA) can be considered violations of the False Claims Act, which opens the way
      to fraud and abuse suits. The scale of penalties involved in these suits may lead
      to more examination of the scope of FDA regulation and commercial speech
      protections. Thus this symposium's consideration of these issues is timely and
      important.

PMID- 21847882
TI  - The ban on "off-label" pharmaceutical promotion: constitutionally permissible
      prophylaxis against false or misleading commercial speech?
AB  - Critics of the Food & Drug Administration's ban on off-label promotion often
      claim that it violates the First Amendment because it suppresses pharmaceutical
      manufacturers' truthful speech about their legal--and beneficial--products.
      Characterizing the ban on off-label promotion in this way has more than
      rhetorical significance. Bans on truthful, non-misleading speech elicit special
      skepticism because of the belief that they "usually rest solely on the offensive
      assumption that the public will respond 'irrationally' to the truth." The
      legislative history of the provisions of the Food Drug and Cosmetic Act that
      underlie the ban on off-label promotion, however, reveals that Congress was
      concerned that physicians were responding rationally to false and misleading
      promotional claims. In this Article, I explore the doctrinal questions raised by
      conceiving of the ban on off-label promotion not as a ban on "truthful speech to
      physicians" but instead as a prophylaxis against false and misleading
      pharmaceutical promotion. I review the evidence that false and misleading claims
      were commonplace before the ban's adoption and persist today, along with the
      enforcement challenges the FDA confronted at that time and would confront were
      the ban lifted, and conclude the government likely could develop the factual
      record necessary to establish that Congress' rejection of an after-the-fact case
      by-case approach to combating false and misleading prescription drug promotion is
      constitutional.

PMID- 21847883
TI  - The commercial speech doctrine in health regulation: the clash between the public
      interest in a robust First Amendment and the public interest in effective
      protection from harm.

PMID- 21847884
TI  - Off-label prescription advertising, the FDA and the First Amendment: a study in
      the values of commercial speech protection.

PMID- 21847885
TI  - The money blind: how to stop industry bias in biomedical science, without
      violating the First Amendment.
AB  - The pharmaceutical and medical device industries use billions of dollars to
      support the biomedical science that physicians, regulators, and patients use to
      make healthcare decisions--the decisions that drive an increasingly large portion
      of the American economy. Compelling evidence suggests that this industry money
      buys favorable results, biasing the outcomes of scientific research. Current
      efforts to manage the problem, including disclosure mandates and peer reviews,
      are ineffective. A blinding mechanism, operating through an intermediary such as
      the National Institutes of Health, could instead be developed to allow industry
      support of science without allowing undue influence. If the editors of biomedical
      journals fail to mandate that industry funders utilize such a solution, the
      federal government has several regulatory levers available, including
      conditioning federal funding and direct regulation, both of which could be done
      without violating the First Amendment.

PMID- 21847886
TI  - Can speech by FDA-regulated firms ever be noncommercial?

PMID- 21847887
TI  - No need for more regulation: payors and their role in balancing the cost and
      safety considerations of off-label prescriptions.

PMID- 21847888
TI  - You can't say that on television: constitutional analysis of a direct-to-consumer
      pharmaceutical advertising ban.

PMID- 21847889
TI  - The real relationship in psychotherapy supervision.
AB  - While the real relationship has long been addressed in psychoanalysis and
      psychotherapy, the matter of the real relationship in psychotherapy supervision
      has yet to receive any attention. Ample supervisory focus has indeed been given
      to the working alliance and transference-countertransference configuration
      (including parallel processes), but after a century of psychotherapy supervision,
      any mention whatsoever of real relationship phenomena is absent. In this paper,
      the following hypotheses are proposed: The real relationship (1) is a crucial
      component of the supervision relationship that has transtheoretical implications;
      (2) exists from the moment supervision begins until its end; (3) is the forever
      silent yet forever substantive contributor to supervisory process and outcome;
      (4) exerts a significant impact on (a) the development and establishment of the
      supervisory working alliance and (b) the unfolding and eventual utilization of
      the transference-countertransference experience in the supervisory situation; (5)
      consists of at least two dimensions in supervision--realism and genuineness--that
      vary along valence and magnitude continua (building on the works of Greenson and
      Gelso), and (6) deserves a place of eminence equal to the working alliance and
      transference-countertransference configuration if supervision theory, practice,
      and research are to be most fully informed. The possibility of using recent real
      relationship research in psychotherapy as a prototype to inform future research
      in supervision is presented, and two case examples are provided to illustrate the
      seeming power of real relationship phenomena in psychotherapy supervision.

PMID- 21847890
TI  - Girls who cut: treatment in an outpatient psychodynamic psychotherapy practice
      with adolescent girls and young adult women.
AB  - The observation of deficits in the capacity for mature emotional self-regulation
      in girls who cut is noted in the literature (Daldin, 1990; Novick & Novick, 1991;
      Nock et al., 2008). The acquisition of the ability to respond in a healthy manner
      to stress and challenge, either from outside or inside the self is one of the
      most important tasks of early development; girls who cut have not accomplished
      this developmental task or are seriously compromised in their efforts to do so.
      The connection between this observation, the psychosexual developmental
      antecedents of this deficit, and psychodynamic approaches to treatment are
      explored in the literature and in case reviews.

PMID- 21847891
TI  - Metaphors as contextual evidence for engaging Haitian clients in practice: a case
      study.
AB  - Haitian immigrants remain underserved in the United States (U.S.), despite their
      large presence and their visibility, which increased after the January 12, 2010
      earthquake. Employing cultural-specific practice strategies to engage Haitians in
      the U.S. who experienced loss in their social networks, requires understanding
      the context of their ecological culture and consideration of relevant linguistic
      and cultural elements. Through a case example, we describe the use of metaphors
      in cultural language as part of a strategy used to engage a Haitian immigrant
      with symptoms of posttraumatic stress disorder. Outcomes indicate that the use of
      storytelling and metaphors facilitate disclosure of clients' worldviews,
      experiences, feelings and hopes in a safe environment while providing them with
      tools to determine progress. We identify four practice guidelines for
      intervention strategies with ethnic minority groups who share similar cultural
      contexts. Metaphors, which are a viable approach to practice, focus on cultural
      strengths and resiliencies over traditional models of deficit and can enhance
      access to needed effective services for underserved populations, such as Haitians
      in the United States.

PMID- 21847892
TI  - Spirituality vis-a-vis Islam as prerequisite to Arab American well being: the
      implications of Eurocentrism for mainstream psychology.
AB  - Due to the historical preponderance of racial and/or intellectual homogeneity in
      the field of psychology, Eurocentrism set the "gold standard" for its method of
      intervention. As such, it might be argued that psychology remains a bastion of
      Eurocentric thought despite the globalization of knowledge and the influx of
      racially and ethnically diverse scientists into the research endeavor. At the
      same time and the significant increase in the immigrant Arab population, Arab
      Americans remain a less familiar component of society. Among the various Arab
      populations, spirituality through Islam is fundamental. Thus, psychologists would
      be remiss to exclude a critical aspect of Arab American life from intervention
      when it is essential to well-being.

PMID- 21847893
TI  - Envelopments: immersion in and emergence from drug misuse.
AB  - Contemporary psychodynamic therapists, as contrasted with early ones, are more
      active and interactive, less dependent on interpretations, and more focused on
      affects, self-regulation, and interpersonal relations, with a premium placed on
      the therapeutic alliance. Evidence supports the utility and effectiveness of the
      psychodynamic paradigm. Two cases are presented that demonstrate how a well
      trained psychodynamic therapist is able to effectively apply such an approach to
      individuals with substance use disorders, in one instance a client in early
      treatment still immersed in her addictions, and, in the second case a client in
      early abstinence emerging from a long standing dependency on alcohol and cocaine.
      The case material highlights the special sensitivities and practices required to
      address predisposing factors and resulting consequences associated with addictive
      disorders. Reflections by the therapist and the clients provide a basis to
      consider the nature of the clients' addictive involvements, a rationale for the
      therapist's interventions, and how client vulnerabilities are addressed in their
      attempts to recover from their addictions.

PMID- 21847894
TI  - The teenager's confession: regulating shame in internal family systems therapy.
AB  - This case study explores the clinical relevance of the differences among shame,
      guilt that is linked with shame, and pure guilt. Empirical literature on emotion
      suggests that shame is instrumental in a host of psychiatric symptoms while pure
      guilt is prosocial and adaptive. Regulating shame and being able to feel pure
      guilt may be especially important for trauma patients like the one described
      here, who have transgressors as well as victims. The protocol of internal family
      systems (IFS), a mode of therapy that utilizes psychic multiplicity and actively
      recruits internal compassion, is described as a treatment for regulating shame
      and facilitating adaptive guilt.

PMID- 21847895
TI  - Symposium on commercial speech and public health.

PMID- 21847896
TI  - Health related claims, the market for information, and the first amendment.

PMID- 21847897
TI  - Truth or consequences?: Commercial free speech vs. public health promotion (at
      the FDA).

PMID- 21847898
TI  - Commercial speech, drugs, promotion and a tailored advertisement moratorium.

PMID- 21847899
TI  - The Food and Drug Administration v. the First Amendment: a survey of recent FDA
      enforcement.

PMID- 21847900
TI  - Hidden truth: The perils and protection of off-label drug and medical device
      promotion.

PMID- 21847901
TI  - Discourse norms as default rules: structuring corporate speech to multiple
      stakeholders.
AB  - This Article analyzes corporate speech problems through the framework of
      corporate law. The focus here is on the "discourse norms" that regulate corporate
      speech to various corporate stakeholders, including shareholders, workers, and
      consumers. I argue that these "discourse norms" should be understood as default
      terms in the "nexus-of-contracts" that comprises the corporation. Having reviewed
      the failure of corporate law as it bears on the interests of non-shareholding
      stakeholders such as workers and consumers, I urge the adoption of prescriptive
      discourse norms as an approach to reforming corporate governance in a socially
      useful manner.

PMID- 21847902
TI  - A veil of tax exemption?: A proposal for the continuation of federal tax-exempt
      status for "nonprofit" hospitals.

PMID- 21847903
TI  - When regulation becomes personal: asserting retaliatory enforcement claims
      against regulatory agencies.

PMID- 21847904
TI  - Born by the woman, caught by the midwife: the case for legalizing direct-entry
      midwifery in all fifty states.

PMID- 21847905
TI  - The foundational documents of professional nursing.

PMID- 21847906
TI  - [GaN-based white-light-emitting diodes with low color temperature and high color
      rendering index].
AB  - The luminescence properties of high color rendering white LED depending on the
      proportions of mixed phosphor powders were investigated by adopting green and red
      phosphors stimulated by a 440 nm InGaN/GaN based blue LED. The results show that
      when the proportion of A/B type silica gels and green/red phosphor powders is 0.5
      : 0.5 : 0.2 : 0.03, two luminance bands are stimulated and their wavelength peaks
      are 535 and 643 nm, respectively. The minimum color temperature can reach 3 251
      K, while the color rendering is as high as 88. 8. Compared with the traditional
      white LED fabricated by yellow YAG-phosphors-coated high efficiency 460 nm blue
      LED, the color temperature is lower and the color rendering index can be
      increased by almost 26%.

PMID- 21847907
TI  - [The effect of temperature on the PL spectra of high power LED].
AB  - Two kinds of 1 W white high power light emitting diode (LED) were made by
      packaging blue chips from Taiwan and US. The chips were coated by the same
      phosphor and transparent silica gel. Optical properties of the two kinds of LEDs
      were investigated in the temperature range of 15-75 degrees C and at the current
      of 350 mA. The results show that temperature badly affects the optical parameters
      such as peak wavelength, radiant flux, color temperature and so on. After
      analyzing the PL spectrum, the relationship between temperature and LED
      performance was found. The reasons for optical parameters vs. temperature were
      theoretically analyzed. Some suggestions were given to reduce the influence of
      temperature on power LED.

PMID- 21847908
TI  - [Effect of mixed interface on the performance of solution-processed
      phosphorescent OLEDs].
AB  - In the present work, in order to improve electron injection and transport at the
      interface of the hole blocking layer (HBL) and the electron transport layer (ETL)
      in the hole-domain solution processed phosphorescent organic light emitting
      devices (PhOLEDs), the mixed interface layer (MIL) was fabricated by partially co
      doping hole blocking material 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP)
      and electron transport material tris(8-quinolinolato) aluminum (Alq3) between
      HBL/ ETL. The MIL thickness was kept at 10nm, while the doping ratio of these two
      materials varied. Under a given electric field, the devices with the MIL at any
      mixed ratios all show much higher luminance and current density than those with a
      typical interface. For example, the luminance power and current density at 10 V
      for a typical device are 1.03 microW and 5.13 mA x cm(-2), while in case of mixed
      interface are 3.64 microW and 18.1 mA x cm(-2), respectively. From data results
      and theoretical analysis, the possible derivation of these improvements is
      considered to be the reduced electron accumulation at the interface resulting
      from the reduced electron injection energy barrier and lowered transport mobility
      by BCP material, which leads to an increase in electron amount in the emission
      layer and therefore the higher luminance and current density.

PMID- 21847909
TI  - [Ultrasonic nebulizer assisted LIBS for detection of trace metal elements
      dissolved in water].
AB  - Because of the complex factors in bulk water, the effect of LIBS on the analysis
      of liquid sample is limited in liquid sample. Under this circumstances, a new
      method of LIBS assisted by ultrasonic nebulizing technology has been introduced.
      According to this method, the liquid sample is transformed into dense droplets by
      ultrasonic nebulizing technology, and these dense droplets are subjected to the
      analysis of LIBS later. Based on this thought, a detection experimental system
      was established, composing of ultrasonic system, 1 064 nm ND: YAG laser, and ICCD
      system. A series of experiments and analysis were carried out to detect the
      magnesium element dissolved in pure water using the detection experimental system
      mentioned above. The results showed that even with a very low laser pulse energy
      (30 mJ), the signals of LIBS still have a long lifetime and a high signal to
      background ratio. The limit of detection for magnesium element could reach as low
      as 0.242 ppm. At the same time, the electron density of plasma was calculated
      utilizing the Halpha line to give the evolution features of plasma induced by
      this new method.

PMID- 21847910
TI  - [Controlled syntheses and photoluminescence characterization of monoclinic cerium
      orthophosphate with nanostructure].
AB  - The nanostructured CePO4 with monoclinic phase was controllably synthesized
      through a low temperature hydrothermal route by varying the reactant PO4(3
      )/Ce(3+) molar ratio. The structures, morphologies, sizes and luminescence
      properties of the products were studied by XRD, FE-SEM, DSC-TG and
      photoluminescence spectra. With the PO4(3-)/Ce(3+) molar ratios increased, the
      synthesis temperature of as-synthesized monoclinic CePO4 was decreased, and the
      morphologies underwent the evolution from the rod-like nano-structures to the
      flower-like nanoclusters. When the PO4(3-)/Ce(3+) molar ratio was lower, CePO4
      nanorods were obtained, while the PO4(3-)/Ce(3+) molar ratio was higher, the
      monoclinic CePO4 flower-like nanoclusters were crystallized. The
      photoluminescence spectrum showed that the CePO4 nanorods exhibit better
      photoluminescent property than the CePO4 flower-like nanoclusters. With the
      cycling use of phosphoric acid, the low-cost preparation of CePO4 could be
      achieved.

PMID- 21847911
TI  - [Study on self-propagating synthesis of the doped SrAl2O4 rare earth long
      afterglow phosphors].
AB  - Twenty one doped SrAl2O4 long after-glowed phosphors with 4 series were
      synthesized by self-propagating high-temperature synthesis method (SHS) with urea
      nitrate solution which served as media at 600 degrees C. They are SrAl2O4:
      Eu(2+)0.012 5, RE(3+)0.012 5 (RE(3+) = Ce(3+), Pr(3+), Nd(3+), Tb(3+), Dy(3+)),
      SrAl2O4 : Eu(2+)0.012 5, M0.012 5 (M = Li(+), Be(2+), Cd(2+), Mn(2+), Cu(2+),
      Ag(+), Zn(2+), Pb(2+)), SrAl2O4 : Eu(2+)0.012 5, Dy(3+)0.012 5, M0.012 5 (M =
      Mn(2+), Cu(2+), Ag(+), Zn(2+)), and SrAlO4 = Eu(2+)0.012 5, Dy(3+)0.012 5,
      RE(3+)0.012 5 (RE(3+) = Ce(3+), Pr(3+), Nd(3+), Tb(3+)), of which luminescence
      and after-glowing features were tested. The morphology of all these samples
      presents a state of porosity and laxity. The samples show an intense emission
      peak at 514 nm and broad peaks of the excitation spectra at 290-360 nm, Tb(3+)
      and Dy(3+) had most effects on luminance and after-glowed time respectively. The
      SrAl2O4 : Eu(2+)0.012 5, Dy(3+)0.012 5 had good luminance and proper after-glowed
      time as well.

PMID- 21847912
TI  - [Flow-injection chemiluminescence determination of trace copper on-line
      separation and enrichment by ion imprinted polymer].
AB  - In the present study, Cu(II)-imprinted polymer was prepared and used as an
      effective method for separation and enrichment of Cu (II) ion in samples. An on
      line preconcentration and extraction flow-injection system using solid phase
      extraction (SPE) column packed with prepared ion imprinted polymer (IIP) was set
      up. The column was eluted with a mixture of ethanol and H2 SO4 after
      preconcentration. A sensitive and simple chemiluminescence (CL) method using flow
      injection has been developed for the determination of copper. The method is based
      on the fact that traces of Cu(II) exert a catalytic action on the oxidation
      between morin by KMnO4 solution. After optimizing the different experimental
      parameters, a calibration graph was obtained over the concentration range of 0 to
      10 microg x mL(-1) for Cu(II) and r = 0.996 8. The detection limit is 0.001 2
      microg x mL(-1). The recoveries are between 95% and 105% and the standard
      relative deviations (RSD) are less than 3% at 4.0 microg x mL(-1) (n = 9) level
      was obtained. The new chemiluminescence determination for copper has been
      established. The method can be satisfactorily applied to the determination of
      copper in sample.

PMID- 21847913
TI  - Utilization of thermal infrared image for inversion of winter wheat yield and
      biomass.
AB  - The present paper utilizes thermal infrared image for inversion of winter wheat
      yield and biomass with different technology of irrigation (drip irrigation,
      sprinkler irrigation, flood irrigation). It is the first time that thermal
      infrared image is used for predicting the winter wheat yield and biomass. The
      temperature of crop and background was measured by thermal infrared image. It is
      necessary to get the crop background separation index (CBSI(L), CBSI(H)), which
      can be used for distinguishing the crop value from the image. CBSI(L) and CBSI(H)
      (the temperature when the leaves are wet adequately; the temperature when the
      stomata of leaf is closed completely) are the threshold values. The temperature
      of crop ranged from CBSI(L) to CBSI(H). Then the ICWSI was calculated based on
      relevant theoretical method. The value of stomata leaf has strong negative
      correlation with ICWSI proving the reliable value of ICWSI. In order to construct
      the high accuracy simulation model, the samples were divided into two parts. One
      was used for constructing the simulation model, the other for checking the
      accuracy of the model. Such result of the model was concluded as: (1) As for the
      simulation model of soil moisture, the correlation coefficient (R2) is larger
      than 0.887 6, the average of relative error (Er) ranges from 13.33% to 16.88%;
      (2) As for the simulation model of winter wheat yield, drip irrigation (0.887 6,
      16.89%, -0.12), sprinkler irrigation (0.970 0, 14.85%, - 0.12), flood irrigation
      (0.969 0, 18.87%, -0.18), with the values of R2, Er and CRM listed in the
      parentheses followed by the individual term. (3) As for winter wheat biomass,
      drip irrigation (0.980 0, 13.70%, -0.13), sprinkler irrigation (0.95, 13.15%, 
      0.14), flood irrigation (0.970 0, 14.48%, -0.13), and the values in the
      parentheses are demonstrated the same as above. Both the CRM and Er are shown to
      be very low values, which points to the accuracy and reliability of the model
      investigated. The accuracy of model is high and reliable. The results indicated
      that thermal infrared image can be used potentially for inversion of winter wheat
      yield and biomass.

PMID- 21847915
TI  - [Determination of chemical oxygen demand in water using near infrared
      transmission and UV absorbance method].
AB  - Chemical oxygen demand (COD) is a synthetical indicator which represents the
      degree of organic pollution in water. The near-infrared (NIR) transmission and
      the UV absorbance method based on photoelectric detection technology and
      spectroscopy analysis have some advantages such as high precision, speed, non
      contact, no secondary pollution etc compared to conventional wet chemical method.
      The NIR transmission spectra and UV absorbance spectra of standard solution
      configured with phthalate hydrogen potassium were collected respectively by MPA
      FTIR spectrometer (Bruker Optics Inc.) made in Germany and AvaSpec-2048-2 UV
      spectrometer (Avantes Inc.) made in Netherlands. After different pretreatment to
      the spectra, COD quantitative analysis model was established using partial least
      squares regression (PLS) and linear regression. The statistical analysis of COD
      quantitative model was implemented, and the result showed that UV absorbance
      method had a higher relevance but lower forecast accuracy and precision than NIR
      transmission method.

PMID- 21847914
TI  - [Research on continuum power regression in noninvasive measurement of human blood
      glucose].
AB  - Accurate measurement of human blood glucose concentration is very significant for
      the treatment of diabetes. In the present paper, the method of continuum power
      regression can improve the predictive accuracy of noninvasive measurement of
      human blood glucose concentration with near infrared spectroscopy. This method is
      the expansion of the traditional method of partial least squares (PLS). It can
      achieve simpleness, and can significantly improve predictive accuracy when the
      power coefficient is fit. Using the method, quantitative analysis models of four
      ingredient experiment and noninvasive experiment of body were established, and
      these models can be used to predict the predictive samples. Experimental results
      show that compared with the PLS, the quantitative analysis models of this method
      not only can improve predictive accuracy, but also can set different power
      coefficient for different individuals to achieve the best results of models.
      According to different individuals, the power coefficient can be selected
      flexibly, which is of great value to the research on noninvasive measurement of
      human blood glucose concentration with near infrared spectroscopy.

PMID- 21847916
TI  - [Assessment of the effects of pressure on sacrum tissue oxygenation using near
      infrared spectroscopy].
AB  - The objective of the present study is to assess the effect of pressure on blood
      oxygenation in the sacrum tissue (high-risk area for pressure ulcer) based on
      near infrared spectroscopy (NIRS) signals. NIRS was used to detect the change in
      the value of blood oxygenation. Thirty subjects were recruited, of which ten were
      elders (average age, 73.4 y ), ten were persons with spinal cord injury (average
      age, 32 y) and ten were healthy persons (average age, 25 y). In resting
      conditions, the blood oxygenation in sacrum tissue of the 30 subjects was
      monitored for 20 minutes prior to and after the three-minute loading period. The
      results show that the first three oxygenation parameters in the elderly and
      persons with spinal cord injury (SCI) changed significantly during the loading
      period (p < 0.01) and took longer time to return to the normal level than the
      health persons. TOI in the three groups decreased with the pressure and returned
      after pressure release. These findings indicated that pressure had significant
      effect on blood oxygenation and the oxygenation parameters are good indicators of
      evaluation of pressure sore risk.

PMID- 21847917
TI  - [Comparative study on FTIR spectra of garlic from different geographical
      populations].
AB  - In the present paper, 25 garlic samples from different geographical populations
      were studied. FTIR spectra for each sample were obtained by using Fourier
      transform infrared spectrometer, and the similarity of garlic samples from
      different geographical populations was compared through "quick comparison"
      function in software of the spectrometer. The results showed that there are
      differences among FTIR spectra of garlic samples from different geographical
      populations. The quick comparison showed that the similarity is from 76.3% to
      99.8% and the diversity of differentiation is more obvious. To some extent, the
      results reflected the effects of populations environment on physical and chemical
      properties of garlic. The study provided a simple, rapid, non-destructive and new
      methods for identification and evaluation of garlic germplasm resources.

PMID- 21847918
TI  - [Study on different ploidy Siraitia grosvenorii and their genetic relationship by
      FTIR].
AB  - Siraitia grosvenorii was an important Chinese traditional medicine. The spectra
      of leaf of diploid, triploid and tetraploid Siraitia grosvenorii were determined
      by Fourier transform infrared spectroscopy (FTIR) with OMNI sampler directly,
      fast and accurately. And based on the indices of wave number-absorbance from
      different bands and through comparison of differences of these infrared spectra
      the ploidy difference and genetic relationship of Siraitia grosvenorii were
      studied by the methods of principal component analysis (PCA) and cluster
      analysis. The results showed that for the ploidy, the position relationship of
      PCA three-dimensional-plot and the distance coefficient of clustering analysis
      plot between diploid and tetraploid were most remarkbly different, and the
      triploid was basically between diploid and tetraploid, so the ploidy was more
      different, the position relationship of PCA and the distance coefficient of
      clustering analysis were further, and the law was: 2 X < 3 X < 4 X. At the same
      time, the genetic relationship was further with each other while the position
      relationship of PCA and distance coefficient of clustering analysis was further
      too. And the genetic relationship of triploid was affected by the different male
      parent while their female parent was the same one. Therefore, using FTIR based on
      PCA and cluster analysis we could reveal the difference of ploidy and the genetic
      relationship between Siraitia grosvenorii to a certain extent. FTIR could be used
      for excellently polyploidy species breeding of Siraitia grosvenorii.

PMID- 21847919
TI  - [Study on rapid determination and analysis of rocket kerosene by near infrared
      spectrum and chemometrics].
AB  - The rocket kerosene quality properties such as density, distillation range,
      viscosity and iodine value were successfully measured based on their near
      infrared spectrum (NIRS) and chemometrics. In the present paper, more than 70
      rocket kerosene samples were determined by near infrared spectrum, the models
      were built using the partial least squares method within the appropriate
      wavelength range. The correlation coefficients (R2) of every rocket kerosene's
      quality properties ranged from 0.862 to 0.999. Ten unknown samples were
      determined with the model, and the result showed that the prediction accuracy of
      near infrared spectrum method accords with standard analysis requirements. The
      new method is well suitable for replacing the traditional standard method to
      rapidly determine the properties of the rocket kerosene.

PMID- 21847920
TI  - [Early detection of corynespora spot on cucumber leaves based on FTIR
      spectroscopy].
AB  - Fourier transform infrared spectroscopy (FTIR) technique was applied in the early
      detection of corynespora spot on cucumber leaves while the symptom had not
      appeared. The cucumber leaves were inoculated with Corynespora cassiicola. By
      observing the changes in the FTIR spectra of infected cucumber leaves at various
      times of post-infection, three sensitive bands, 1 735, 1 545 and 1 240 cm(-1)
      were selected for the identification of cucumber corynespora leaf spot. According
      to the peak areas at these sensitive bands, cucumber leaf samples infected with
      C. cassiicola and control uninfected leaf samples could be classified correctly.
      Results clearly demonstrated that the FTIR technology is an available one for the
      early detection of corynespora spot on cucumber leaves while the symptom has not
      appeared and it provides a new method for the early detection of corynespora
      spot.

PMID- 21847921
TI  - [Study on estimation of fall dormancy in alfalfa by near infrared reflectance
      spectroscopy and support vector machine model].
AB  - The present study proposes a new approach to producing accurate estimates of fall
      dormancy (FD) in alfalfa in a rapid manner. Using near infrared spectroscopy, the
      approach produces results fast without causing damage to samples. Near infrared
      reflectance spectroscopy was applied to measuring the spectra of samples. Then
      principal component analysis (PCA) was conducted on the measurements. The top ten
      principal components were selected based on their cumulative contribution rates
      to build a support vector machine (SVM) model. Detailed analysis and discussions
      were conducted over their parameter and kernel classifications. The experiment
      found that when c = 0.339 2 and g = 32, the accuracy of the predictions of the
      test set can reach 98.182%. Therefore the approach can estimate the FD in alfalfa
      in a rapid and accurate manner. Moreover, it was compared with other approaches
      such as principal component regression, partial least squares regression, BP
      neural networks, and LVQ neural networks. The comparisons have shown that the PCA
      SVM model can effectively address the small-sample-size problem and avoid local
      minimum.

PMID- 21847922
TI  - [Gaussian process regression and its application in near-infrared spectroscopy
      analysis].
AB  - Gaussian process (GP) is applied in the present paper as a chemometric method to
      explore the complicated relationship between the near infrared (NIR) spectra and
      ingredients. After the outliers were detected by Monte Carlo cross validation
      (MCCV) method and removed from dataset, different preprocessing methods, such as
      multiplicative scatter correction (MSC), smoothing and derivate, were tried for
      the best performance of the models. Furthermore, uninformative variable
      elimination (UVE) was introduced as a variable selection technique and the
      characteristic wavelengths obtained were further employed as input for modeling.
      A public dataset with 80 NIR spectra of corn was introduced as an example for
      evaluating the new algorithm. The optimal models for oil, starch and protein were
      obtained by the GP regression method. The performance of the final models were
      evaluated according to the root mean square error of calibration (RMSEC), root
      mean square error of cross-validation (RMSECV), root mean square error of
      prediction (RMSEP) and correlation coefficient (r). The models give good
      calibration ability with r values above 0.99 and the prediction ability is also
      satisfactory with r values higher than 0.96. The overall results demonstrate that
      GP algorithm is an effective chemometric method and is promising for the NIR
      analysis.

PMID- 21847923
TI  - [Preparation of EVOH film and infrared spectroscopic study of its heat
      preservation property].
AB  - EVOH, PE and EVA films were prepared by extrusive blowing techniques, the optic
      capability, transmittance, haze, infrared anti-transmittance and heat
      preservation of the films were studied by IR spectroscopy and optic block. The
      result indicated that the haze degree of the EVOH film decreased about 10% and 5%
      compared to PE film and EVA film respectively, EVOH film's transmission of IR is
      much less than other films in the 2.5-25 microm wavelength range, it is just
      9.03% in 7-14 microm wavelength range, and about 27% less than EVA film, while
      much less than PE film. It was found that EVOH film has much better capability of
      infrared anti-transmittance and point-blank light transmission than other two
      kinds of films. It was good for calefaction and heat preservation of greenhouse.

PMID- 21847924
TI  - [Fast determination of contents of nutrients and stone powder in compound
      fertilizer using near infrared diffuse reflectance spectroscopy].
AB  - In the present paper, a new approach to fast determination of contents of
      nutrients, including total nitrogen content (N), P2O5 content (P) and K2O content
      (K), and of stone powder content in compound fertilizer composed of urea,
      ammonium dihydrogen phosphate, potassium chloride and stone powder was proposed
      using near infrared diffuse reflectance spectroscopy. PLS models of N, P and
      stone powder content were built with the SEP values of 0.8, 0.8 and 1.4
      respectively. The information on which stone powder content model was built is
      the spectrum of crystal water existing in stone powder. K content was calculated
      using other ingredientcontents by normalization principle with a SEP value of
      1.5. Although the SEP values are a little larger than the reproducibility errors
      of the GB/T methods which are conventional methods, the new method can be
      accepted by situ quality control in the production process of compound
      fertilizer.

PMID- 21847925
TI  - [In situ Raman spectroscopic observation of micro-processes of methane hydrate
      formation and dissociation].
AB  - Micro laser Raman spectroscopic technique was used for in situ observation of the
      micro-processes of methane hydrate formed and decomposed in a high pressure
      transparent capillary. The changes in clathrate structure of methane hydrate were
      investigated during these processes. The results show that, during hydrate
      formation, the Raman peak (2 917 cm(-1)) of methane gas gradually splits into two
      peaks (2 905 and 2 915 cm(-1)) representing large and small cages, respectively,
      suggesting that the dissolved methane molecules go into two different chemical
      environments. In the meantime, the hydrogen bonds interaction is strengthened
      because water is changing from liquid to solid state gradually. As a result, the
      O-H stretching vibrations of water shift to lower wavenumber. During the
      decomposition process of methane hydrates, the Raman peaks of the methane
      molecules both in the large and small cages gradually clear up, and finally turn
      into a single peak of methane gas. The experimental results show that laser Raman
      spectroscopy can accurately demonstrate some relevant information of hydrate
      crystal structure changes during the formation and dissociation processes of
      methane hydrate.

PMID- 21847926
TI  - [Raman spectra study of barite at the pressure of 0-1 GPa and ambient
      temperature].
AB  - The variation characters of Raman spectra of S-O symmetric stretching vibration
      v987 and symmetric bending vibration v452 and V462 of barite at high pressure
      were studied using moissanite anvil cell. The experimental results show that
      barite is stable at the pressure of 0-1 GPa and ambient temperature, and the
      Raman peak positions of barite shift to higher frequency with increasing
      pressure. The relations between the Raman shifts and system pressure are given as
      follows: v987 = 0.004 4p+987.42, v452 = 0.002 3p+452.6, v462 = 0.001 8p+ 462.42,
      and that stretching vibrations are more affected by pressure than bending
      vibrations. The intensity of 987 cm(-1) Raman peak of barite is six times greater
      than that of 464 cm(-1) Raman peak of quartz, so barite can be used as a good
      pressure gauge. Besides, the relation between the system pressure and Raman shift
      of 987 cm(-1) peak position of barite is given as follows: p(MPa) = 223.16 X
      (deltav(p))987 -90.35 (987 cm(-1) < v(p) < 992 cm(-1)). The difference in the
      measured relative pressure-shift of the Raman line of the symmetric stretching
      vibration among various sulfate minerals shows the compressibility and strength
      of the S-O bond in the SO4 group.

PMID- 21847927
TI  - [Interaction of lactoferrin and its peptides with DPPC and DPPG liposomes studied
      by Raman spectroscopy].
AB  - Interaction of lactoferrin and its peptides LfcinB4-14 and LfampinB with
      dipalmitoylglycero-phosphocholine (DPPC) and dipalmitoylglycero-phosphoglycerol
      (DPPG) liposomes were studied by means of Raman spectroscopy. In our study,
      conformational changes in the phospholipid molecules were investigated by
      measuring the intensities of 2 847 and 2 882 cm(-1) Raman bands which are
      assigned to acyl chains' symmetric and asymmetric C-H stretching vibrations. The
      addition of lactoferrin and its peptides LfcinB4-14 and LfampinB caused a
      decrease in the 2 882 cm(-1) intensity of DPPG liposomes, thus the order
      parameter for the lateral interactions between chains S(lat) decreased from 0.19
      to 0.17, 0.14 and 0.12 respectively. On the contrary, the intensities at 2 847
      and 2 882 cm(-1) of DPPC liposomes were poorly affected by lactoferrin and its
      peptides. The results show that lactoferrin and its peptides present a stronger
      effect on the molecular structure and order degree of anionic lipid DPPG than
      that of zwitterionic lipid DPPC. This suggests that lactoferrin, LfcinB4-14 and
      LfampinB can interact and combine with the negatively charged DPPG liposomes by
      electrostatic interaction and perform its antibacterial activity. Besides,
      LfcinB4-14 and LfampinB can affect the lipid more strongly than lactoferrin.

PMID- 21847928
TI  - [Secondary structure changes of insulin induced by PEF exposure at different
      temperatures using Raman spectra and theoretical model analysis].
AB  - Recently, biological effects induced by weak electromagnetic fields have been a
      public concern. Our previous study found temperature and electromagnetic field co
      effects on insulin conformation. Therefore, in the present study, Raman
      spectroscopy was employed to investigate the secondary structure changes of
      insulin molecule induced by pulsed electric field (PEF) exposure at various
      temperatures. The content changes in alpha helix of insulin were obtained. Then,
      protein helix-random coil transition model was used to quantitatively study the
      experimental results. The theoretical model could figure out the effect of PEF on
      alpha helix contents of insulin at different temperatures. The protein secondary
      structure transits from helix to random coil evoked by PEF exposure and change of
      thermodynamic environment, which could explain the reason for the decline of
      alpha helix content of insulin caused by PEF exposure together with temperature
      rising. The results offer experimental basis and theoretical reference for
      further study of the mechanism of nonthermal effects of weak electromagnetic
      fields on biological molecule secondary structure.

PMID- 21847929
TI  - [Raman scattering calculations studies of malachite green isothiocyanate].
AB  - Malachite green isothiocyanate (MGITC) is a Raman probe molecule that was applied
      to cells detection, tissue composition detection and cells stain imaging. In the
      present work, MGITC molecular structure was optimized by density functional
      theory(DFT) calculation. MGITC molecular Raman spectra and infrared spectra were
      calculated with Hartree-Fork theory and MP2 theory based on STO-3G level, then
      two theoretical Raman spectra were carefully compared with experimental spectra,
      and good agreements were obtained between the theoretical and experimental
      results. MGITC structure parameters were given also in the paper including bond
      lengths and bond angles etc. Vibrational modes were assigned to all bands in the
      range between 550 and 4 200 cm(-1). This work will facilitate the application of
      MGITC Raman probe for biology.

PMID- 21847930
TI  - [Preparation and study of a new type substrate for Raman enhancement].
AB  - A highly ordered anodic aluminum oxide template was prepared, the mixture of
      phosphate and chromic acid was used to remove the oxide layer, regular pits array
      on the surface of the aluminum was obtained, then AC electrodeposit method was
      used to get fluffy nano silver structure, which was tested with SEM. Melamine was
      chosen as the probe molecule, the Raman peaks of melamine with 10(-12) g x mL(-1)
      were successfully detected, and the molecule number of the melamine is about 3.8
      x 10(-6) at this concentration and laser spot through calculation, which is
      beyond the detection level of monolayer. The enhancement factor reached 1.41 x
      10(11).

PMID- 21847931
TI  - [Study on the vibrational spectra characters of Taiwan blue chalcedony].
AB  - Blue chalcedony is one of the precious gems produced in Taiwan, known as "Taiwan
      Sapphire" in the world. The infrared absorption spectrum and Raman spectrum were
      employed to study the characters of the vibrational spectrum of the blue
      chalcedony with different color and texture. It was indicated that the Taiwan
      blue chalcedony shows the typical spectral characteristics of the vibrational
      spectra of the quartziferous jade. The infrared absorption spectra show that the
      strongest absorption region 1 250-1 110 cm(-1) is induced by Si-O asymmetric
      stretching vibration, the medium-intensity absorption band 800-600 cm(-1) is
      mainly induced by the Si-O-Si symmetric stretching vibration and the Si--O
      bending vibration displays the peaks in the range of 600-300 cm(-1). The Raman
      spectra scattering peaks of the Taiwan blue chalcedony samples are mainly at 499
      cm(-1) +/-, 464 cm(-1) +/-, and 208-214 cm(-1) and are mainly induced by the Si-O
      symmetric bending vibration, Si-O bending vibration, and [SiO4] rotational
      vibration or translation vibration of the "Moganite" quartz.

PMID- 21847932
TI  - [Research on using a mono-window algorithm for land surface temperature retrieval
      from Chinese satellite for environment and natural disaster monitoring (HJ-1B)
      data].
AB  - Land surface temperature(LST) is a key parameter in earth environment, the
      thermal infrared band that can detect LST plays an important role in
      spectroscopy. Aiming to the latest optical and thermal bands of HJ-1B satellite,
      the LST retrieval over Ningxia plain was implemented using a mono-window
      algorithm without atmospheric water vapor content input, based on the COST model
      for atmospheric correction. Considering the difficulty of obtaining simultaneous
      ground measured data, the MODIS LST product was adopted as a standard to test the
      approach. The comparison and validation indicate that this method has good
      reliability with accuracy of less than 1 K. In addition, the sensitivity analysis
      is performed for land surface emissivity, and the result shows that this variable
      was not sensitive to LST, because the LST error is less than 0. 5 K when it
      varies at me dium level. This study proves that the satellite data has higher
      availability for detecting LST.

PMID- 21847933
TI  - [New index for soil moisture monitoring based on deltaT(s)-albedo spectral
      information].
AB  - Monitoring soil moisture by remote sensing has been an important problem for both
      agricultural drought monitoring and water resources management. In the present
      paper, we acquire the land surface temperature difference (deltaT(s)) and
      broadband albedo using MODIS Terra reflectance and land surface temperature
      products to construct the deltaT(s)-albedo spectral feature space. According to
      the soil moisture variation in spectral feature space, we put forward a simple
      and practical temperature difference albedo drought index (TDADI) and validate it
      using ground-measured 0-10 cm averaged soil moisture of Ningxia plain The results
      show that the coefficient of determination (R2) of both them varies from 0.36 to
      0.52, and TDADI has higher accuracy than temperature albedo drought index (TADI)
      for soil moisture retrieval. The good agreement of TDADI, Albedo/LST, LST/ NDVI
      and TVDI for analyzing the trends of soil moisture change supports the
      reliability of TDADI. However, TDADI has been designed only at Ningxia plain and
      still needs further validation in other regions.

PMID- 21847934
TI  - [Fluorescence properties of urban water bodies of Beijing].
AB  - "Fluorescence fingerprint" of water body based on fluorescence excitation
      emission matrix has been a novel and valuable method to exhibit the organics
      details. In the present study, the fluorescence matrixes of urban water bodies of
      Beijing were investigated. The experimental results showed that these matrixes
      could be divided into 3 groups: Type I owned two fluorescence centers, locating
      at lambda(ex)/lambda(em) = 275-280/340 and 225-230/340 nm respectively, and was
      the predominant group; fluorescence centers of Type II located at
      lambda(ex)/lambda(em) = 280/345-365 and 245/380 nm; Type II had four fluorescence
      centers around 275/305, 275/340, 225/305 and 225/340 nm. The fingerprints
      indicated that these water bodies had been disturbed by human activities. Type I
      and Type III were transitional fingerprints between undisturbed water body and
      sewage wastewater and Type III was closer to sewage wastewater. Type II closely
      originated from reclaimed water of municipal wastewater treatment plant. These
      three types were main types of urban water bodies where domestic pollution was
      dominating. The fluorescence fingerprints clearly displayed the ubiquitous
      impacts of human activities and the resulting potential risk. Fluorescence
      fingerprint could display pollution information and serve as a possible diagnosis
      tool of pollution source.

PMID- 21847935
TI  - [Study on fluorescence measurement system of wastewater treatment process].
AB  - The present paper, focusing on the relationship between the fluorescence
      characteristics of fluorescent substances produced by the anaerobic reactors in
      process of the wastewater treatment status, aims to build an online detection
      platform of anaerobic wastewater treatment process for the wastewater treatment
      process parameter control, to provide effective, credible and stable technical
      basis, and to a certain extent can improve the efficiency of wastewater
      treatment. The results showed that it is feasible for this system to use
      fluorescence spectroscopy of wastewater treatment anaerobic reactor during the
      test; compared with the conventional detection method, it has simple structure,
      high sensitivity, and less time-consuming advantages; for other fluorescent
      substances in waste water treatment, it has broad application prospects.

PMID- 21847936
TI  - [Effect of temperature and pH on the fluorescence characteristic of oily waste
      water].
AB  - The present study was about the effect of temperature (5-55 degrees C) and pH (3
      12) value on the fluorescence characteristic of oily waste water from the export
      of China Petroleum & Chemical Oil Refinery. It was found that temperature only
      affects the fluorescence intensity but not the site of fluorescence peaks. The
      fluorescence peaks shift right that from 413 to 426.5 nm when the oily waste
      water is acid. And along with the enhancing of the acidity the fluorescence
      intensity ascended. The fluorescence intensity decreased with alkaline enhancing
      but the site of fluorescence peaks remained unchanged at 398 nm. Temperature and
      pH value were the two important impact factors on the fluorescence characteristic
      of oily waste water. If desired it needs correction and compensation on
      temperature and pH value. That's expected to improve the detection accuracy of
      oil class and content.

PMID- 21847937
TI  - [The variation trend of fluorescence characteristics of DOM in the acetophenone
      degradation process by electro-Fenton].
AB  - In the acetophenone degradation process by electro-Fenton, the variation trend of
      fluorescence characteristics of dissolved organic matter (DOM) in acetophenone
      synthetic wastewater was detected by excitation-emission matrix (EEM)
      fluorescence spectra. The fluorescence spectra characteristics of acetophenone
      were studied, and the fitting line of fluorescence intensity and acetophenone
      removal efficiency was discussed in detail. The results show that the locations
      of the two fluorescence centers of acetophenone synthetic wastewater are at
      lambda(Ex/Em) = 270/305 nm (Peak A) and lambda(Ex/Em) = 215/305 nm (Peak B),
      respectively, and the ratio of Peak A/Peak B is 1.22. In the electro-Fenton
      treatment process, firstly, acetophenone was decomposed into unsaturated fatty
      acid which had stronger fluorescence intensity, further, it was degraded into
      short-chain small molecular compounds which have weaker fluorescence intensity.
      Therefore, the fluorescence intensity of synthetic wastewater was increased at
      first and decreased afterwards in the entire 180 min electro-Fenton treatment
      process. The two-dimensional fluorescence peak at 285-375 nm of emission
      wavelength (at lambda(Ex) = 250 nm) had a good linear relationship with the
      removal efficiency of acetophenone, therefore, it could reflect effectively the
      removal efficiency of acetophenone in the whole electro-Fenton treatment process.

PMID- 21847938
TI  - [Application of fluorescence spectroscopy in studying the protective function of
      11-amino acid motif of group3 late embryogenesis abundant protein].
AB  - Late embryogenesis abundant protein (LEA) can enhance the tolerance of organisms
      under drought, low-temperature and other stress conditions. However, their
      protection mechanisms are still unclear. In the present paper, the peptides
      consisting of multi-copies of 11-amino acid motif, such as PM2D and PM2E are
      proved to protect the activity of the lactate dehydrogenase (LDH) from freeze
      thaw by using ultroviolet spectrometry. Furthermore, the fluorescence
      spectroscopic results show that the peptide consisting of multi-copies of 11
      amino acid can stabilize the structure of LDH through synergy and multi-sites
      binding. However, the peptides consisting of less copies of 11-amino acid, such
      as PM2F and PM2G bind to LDH through one site, and the binding is weak. They thus
      can not protect the activity of LDH. In addition, the peptides consisted of multi
      copies of 11-amino acid protect LDH by acting with trehalose synergically, and
      the protection mechanisms of LEA and trehalose on LDH are different.

PMID- 21847939
TI  - [Interaction of cucurbit [n = 7, 8] with methylindoles via fluorescence
      spectroscopy].
AB  - In the present work, the authors investigated interaction of cucurbit [n=7, 8]
      urils(Q[7], Q[8]) with 2-methylindol (Me) and 3-methylindol(Sk), influences of pH
      and temperature on the interaction of Q[7], Q[8] with the guests and calculations
      of the stability constants and thermodynamic parameters by using fluorescence
      spctroscopy. The results show that: the interation ratios are 1 : 1 of host:
      guest for all systems, except the Q[8]-Sk system, for which the ratio is 1 : 2 of
      host: guest; the interaction ratios of the host: guest systems did not change in
      the range of pH 1-11 and temperature between 298 and 313 K; the stability
      constant is the largest at pH 1 and room temperature. The thermodynamic parameter
      revealed that the interaction of the host and the guest of spontaneitied.

PMID- 21847940
TI  - [The spectroscopic properties of a new rhodamine B Schiff-base fluorescent
      derivative].
AB  - A derivative with Schiff-base structure was synthesized. Fluorescence and visible
      absorption spectra show that the presence of Fe3+ induces the formation of a Fe3+
      complex, observing significant enhancement of fluorescence and absorption. The
      results show that the derivative is not only a good fluorescence and colorimetric
      chemosensor for Fe3+, but also a metal complex fluorescent probe for BSA.

PMID- 21847941
TI  - [Determination of cetirizine dihydrochloride by anti-fluorescence quenching on
      rhodamine B-sodium tetraphenylborate system].
AB  - The sodium tetraphenylboron has the fluorescence quenching effect on rhodamine B,
      making the fluorescence signal intensity weaken or even disappear. But cetirizine
      dihydrochloride has the anti-quenching effect on rhodamine B--the fluorescence
      signal is enhanced, and there was a linear relationship between the fluorescence
      signal enhancement degree and drug concentration. In the present paper, 491 and
      610 nm were chosen as the excitation and emission wavelength for measurement of
      the fluorescence intensity difference deltaF = F1 - F0 of blank solution and test
      solution, and according to positive correlation between the value of deltaF and
      cetirizine hydrochloride concentration of test solution, a new method of anti
      fluorescence quenching for the determination of cetirizine hydrochloride was
      established. The linear regression equation was deltaF = 0.727 5m - 2.357,
      correlation coefficient was 0.997 2, linear range was 3.50-129.3 mg x L(-1), the
      detection limit was 1.05 mg x L(-1) and RSD was 1.2%. The cetirizine
      hydrochloride tablets and cetirizine hydrochloride capsules from different
      manufacturers were determined by this method, the measured values were basically
      in line with the labeled amount of drugs, and the recovery rate was between 92%
      and 106%.

PMID- 21847942
TI  - [Spectroscopic studies on the interaction of Elsinochrome A with myoglobin].
AB  - The interaction between Elsinochrome A (EA) and myoglobin (Mb) was investigated
      using UV-Vis and fluorescence spectroscopy. The results suggested that there was
      a strong interaction between EA and Mb. In the dark, the interaction occurred on
      the surfaces amidic acid of Mb, but when illuminated, the interactions happened
      both on amidic acid and the interior structure of hemachrome of Mb. According to
      the values of the quenching constant, the thermodynamics parameters, the binding
      constants and the binding sites, it was showed that the binding interaction of EA
      and Mb was mainly hydrophobic in nature and the quenching mechanism was static
      quenching procedure. The change in the micro-circumstance of aminos of myoglobin
      was studied by synchronous fluorescence spectroscopy.

PMID- 21847943
TI  - [Investigation of material structure and optical property of transmission-mode
      GaN photocathode by ultraviolet transmission spectral].
AB  - GaN UV photocathode has become a high-performance vacuum ultraviolet detectors in
      recent years. As the photocathode practical application mode, transmission-type
      multilayer structure and its optical property have important influences on
      photocathode photoemission performance. Ultraviolet transmission spectra of
      transmission-mode GaN photocathode were measured. The optical transmission model
      of transmission-mode GaN photocathode was built, and based on the model the
      functional relations of thin film thickness and optical adsorption coefficient
      with transmission spectral were deduced. The error of calculated GaN epitaxial
      thickness with respect to actual value is very small, and calculated adsorption
      coefficients are consistent with reported data. It was shown that material
      structure and optical property of transmission-mode GaN photocathode can be
      evaluated accurately by this ultraviolet transmission spectral method.

PMID- 21847944
TI  - [Spectrometric study on the effect of denaturant on the conformation of tartary
      buckwheat protein].
AB  - The effect of ethanol and GuHCl solution on the structure of tartary buckwheat
      protein (TBWSP31) was studied by UV differential absorption and fluorescence
      emission spectra. The alcohol denaturation of TBWSP31 was a kind of partial
      denaturation. The hydrophobic core of TBWSP31 remained intact and the
      conformation of the hydrophilic shell was changed. When TBWSP31 was denatured by
      GuHCl solution with higher concentration, Tyr and Trp residues were exposed to
      the polar aqueous solvents from the hydrophobic core, and the microenvironment
      showed a great change.

PMID- 21847945
TI  - [Study on the method of recognizing abandoned farmlands based on multispectral
      remote sensing].
AB  - Being abandoned for farmland seriously affected China's grain output for
      farmlands. It has become an important phenomenon over the past 20 years in China.
      Multispectral remote sensing has the advantage of wide range and high speed in
      requiring data. It has great potential in the research on land use. Therefore, to
      extract abandoned farmland in China, the authors' used the NDVI data of
      Modis/Terra from 2000 to 2009 which is one of multispectral remote sensing data
      and the Remote Sensing Image of ALOS satellite in Japan. The authors' used the
      parameter of NDVI of time series to describe the character of the main land use
      types. After drawing the time-series curves of the main land use type samples,
      the authors' analyzed them with consulting the life character of these types.
      Then, the authors' compared these curves; finally we recognized abandoned
      farmland from the others. At last the authors' went to experimental plot to
      survey the land use. The results demonstrated that the method of using
      multispectral remote sensing data can abstract abandoned farmland and classify
      the main kind of land use, and the accuracy is as high as 90%. So the method is
      feasible in recognizing abandoned farmland.

PMID- 21847946
TI  - Indication of the expression of transgene in rice plant based on hyperspectral
      remote sensing technique II--growth monitoring of samples in the contrast
      experiment.
AB  - Since the complication of monitoring and evaluating the problems about the
      transgenic expression and its impacts on the receptor in the transgenic crop
      breeding and other relevant evaluated works, the authors in the present work
      tried to assess the differences of spectral parameters of the transgenic rice in
      contrast with its parent group quantitatively and qualitatively, fulfilling the
      growth monitoring of the transgenic samples. The spectral parameters (spectral
      morphological characteristics and indices) chosen are highly related to internal
      or external stresses to the receipts, and thus could be applied as indicators of
      biophysical or biochemical processes changes of plant. By ASD portable field
      spectroradiometer with high-density probe, fine foliar spectra of 8 groups were
      obtained. By analyzing spectral angle and continuum removal, the spectral
      morphological differences and their locations of sample spectra were found which
      could be as auxiliary priori knowledge for quantitative analysis. By
      investigating spectral indices of the samples, the quantitative differences of
      spectra were revealed about foliar chlorophyll a+b and carotenoid content. In
      this study both the spectral differences between transgenic and parent groups and
      among transgenic groups were investigated. The results show that hyperspectral
      technique is promising and a helpful auxiliary tool in the study of monitoring
      the transgenic crop and other relevant researches. By this technique,
      quantitative and qualitative results of sample spectra could be provided as prior
      knowledge, as certain orientation, for laboratory professional advanced
      transgenic breeding study.

PMID- 21847947
TI  - [Stereoscopic remote sensing used in monitoring Enteromorpha Prolifra disaster in
      Chinese Yellow Sea].
AB  - In the summer 2008, Enteromorpha Prolifra broke out in Yellow Sea and East Sea on
      a large scale for the first time, and became a marine disaster. The authors
      constructed a stereoscopic monitoring system which monitored the disaster
      continuously, dynamically and in real time. The present paper introduced the
      construction of the stereoscopic monitoring system; through analyzing the
      spectral characteristics of Enteromorpha Prolifra and ocean water which were
      acquired in a field experiment, confirmed Enteromorpha Prolifra retrieval models
      based on multi-platform multi-sensor and multi-spectral remote sensing data,
      contrasted the different scale monitoring results, and analyzed the evolvement
      rules with time-series analysis. This system was applied to the Enteromorpha
      Prolifra emergency monitoring in the 29th Olympic sailing area. It was proved
      feasible and valuable for the Olympic safeguard.

PMID- 21847948
TI  - [Analysis of Lop Nur "Ear" features in remote sensing image and its environmental
      meaning].
AB  - There is a great significance of revealing the characteristics of regional
      environment evolution and global change to the research on arid Lop Nur areas. By
      the "Ear" features of Lop Nur in remote sensing image, the spectrum, soil and
      surface parameters were analyzed. The differences in total salt content in soil
      and the surface structure bring are cause directly for the "Ear" features in
      remote sensing image; The results of the analysis of spectrum, total salt content
      and particle size are in good agreement. "Ear" features recorded the process of
      environmental change. The process implys that Lop Nur dried up gradually under
      the impact of global change. The adjustment during the process of drying up let
      Lop Nur experience two relatively humid climates, with the previous a little
      longer, the later very short.

PMID- 21847949
TI  - [Mineral information extraction for hyperspectral image based on modified
      spectral feature fitting algorithm].
AB  - Spectral feature fitting (SFF) algorithm has been frequently used since 1990s. A
      modified spectral feature fitting method is introduced here, which can solve some
      drawback of the general algorithm. The method mentioned here combines SFF with
      user-defined constraints in spectral absorption feature to extract more accurate
      target information from hyperspectral image. Two experiments are presented
      herein, in which three algorithms are used to obtain mineral information from
      hyperspectral data with different space resolution and SNR. Muscovite, calcite
      and chlorite etc. are extracted by general SFF, modified SFF and spectral angle
      mapping (SAM) respectively, and the result indicates that modified SFF algorithm
      is more effective in differentiating subtle spectral feature and obtaining
      accurate mineral information. The experiments also demonstrate that the algorithm
      mentioned here is validated in mineral information extraction.

PMID- 21847950
TI  - [Monitoring "green tide" in the Yellow Sea and the East China Sea using multi
      temporal and multi-source remote sensing images].
AB  - Landsat-TM (Theme Mapper) and EOS (Earth Observing System)-MODIS (MODerate
      resolution Imaging Spectrora-diometer) Terra/Aqua images were used to monitor the
      macro-algae (Ulva prolifera) bloom since 2007 at the Yellow Sea and the East
      China Sea. At the turbid waters of Northern Jiangsu Shoal, there is strong
      spectral mixing behavior, and satellite images with finer spatical resolution are
      more effective in detection of macro-algae patches. Macro-algae patches were
      detected by the Landsat images for the first time at the Sheyang estuary where is
      dominated by very turbid waters. The MODIS images showed that the macro-algae
      from the turbid waters near the Northern Jiangsu Shoal drifted southwardly in the
      early of May and affected the East China Sea waters; with the strengthening east
      asian Summer Monsoon, macro-algae patches mainly drifted in a northward path
      which was mostly observed at the Yellow Sea. Macro-algae patches were also found
      to drift eastwardly towards the Korea Peninsular, which are supposed to be driven
      by the sea surface wind.

PMID- 21847951
TI  - [Simulation and analysis of polarization characteristics for real sea surface
      sunglint].
AB  - The sea surface sunglint is caused by specular reflectance. Water is a kind of
      dark target with a very low reflectance, so sunglint becomes a big noise in the
      aerial or aerospace remote sensing images; sunglint is strongly polarized, and
      can be a natural standard light source for polarized sensor in-flight
      calibration; sunglint also can be utilized to retrieve gaseous constituents and
      aerosol properties. For both de-noising and being standard light source, the
      radiative physic parameters should be calculated accurately. First, A 3-D sea
      surface model was constituted according to the Cox & Munk model; Second, the
      polarized radiative model of sunglint was deduced based on the 3-D sea surface
      model and polarized Fresnel reflectance law; Third, the sensitivities of solar
      viewing relative azimuth, zenith, wind speed and wind direction were analyzed
      utilizing the polarized radiative model. The polarization characteristics
      analysis of sunglint provides a theoretical basis for the quantitative remote
      sensing retrievals which uses sunglint.

PMID- 21847952
TI  - [High speed transmission system for dual-spectral remote sensing system].
AB  - In order to realize dual-spectral aerial camera image data transmission, a novel
      optical transmission system is proposed, then transmission scheme, structure of
      data frame and timing recovery method are discussed thoroughly. First, valid data
      in one line are picked up from two detectors before transmitting, a timing
      recovery method which makes in-out data timing and format consistent, is proposed
      using line valid interrupt flag. Second, based on transmitting and receiving
      buffering mechanism, dual asynchronous detectors data are transmitted in a single
      fiber. Third, transmitting and receiving systems are implemented using large
      programmable devices which embeds high speed data interface. Finally, behavioral
      and system verification method is proposed as well. Experimental results indicate
      that the system could support full, median and base cameral link protocol, serial
      data transmitting speed could be 6.25 Gb x s(-1), and pixel data rate is 40 MHz
      at most for two detectors. It is very suitable for space and serial remote
      sensing equipment due to its compact and high reliable structure.

PMID- 21847953
TI  - [Wheat leaf area index inversion using hyperspectral remote sensing technology].
AB  - The wheat leaf area index (LAI) was inverted using hyperspectral remote sensing
      technology in the present paper. Eighteen kinds of hyperspectral indices were
      comparatively analyzed, and the index OSAVI, which could reflect wheat LAI most
      sensitively, was screened out. The models for wheat LAI inversion were built
      using the field spectra as the training samples. The study showed that the
      calibration R-square and prediction R-square of the inversion model which were
      built by hyperspectral index OSAVI were 0.823 and 0.818, respectively, higher
      than that of other indices, indicating that the accuracy was highest. The
      inversion model was spatially quantitatively expressed in OMIS image, and then
      the inversion value and measured value was compared by the method of regression
      fitting. The R-square and RMSE of the fitting model were 0.756 and 0.500,
      respectively, indicating that the similarity between the inversion value and
      measured value was high. The result showed that it was feasible to invert the
      wheat LAI by hyperspectral indices, and OSVAI was an optimal one.

PMID- 21847954
TI  - [Studies on characterization of humic acids extracted from sediments in Chongqing
      section of the Jialingjiang River].
AB  - Humic acids (HAs) were extracted from sediments of different segments in the
      Jialingjiang River. Fluorescence spectroscopy, elemental analysis and Fourier
      transform infrared (FTIR) spectrometry were used to investigate the chemical
      composition and structure characteristics of HAs. Elemental analysis showed that
      H/C, O/C, and C/N molar rations were significantly different among 4 HAs, which
      indicated their differences in chemical composition and structure
      characteristics. FTIR spectra revealed that HAs contained more carboxyl, hydroxyl
      and carbonyl functional groups, and aromatic structure was very obvious. The
      three dimensional fluorescence excitation-emission-matrix (3DEEM) spectra of HAs
      presented two main peaks (peak a and peak b) at Ex/Em = 270/390 nm and Ex/Em =
      230/350 nm. The relative fluorescence intensities i(A)/I(b) varied from 1.31 to
      2.53 for different HA samples, which revealed that they contained multiple
      molecule fluorophores. Fluorescence index (f4550/500 = 1.43-1.53) suggested that
      HAs mainly originated from terrestrial sources.

PMID- 21847955
TI  - [Design of plant leaf bionic camouflage materials based on spectral analysis].
AB  - The influence of structure parameters and contents of plant leaves on their
      reflectance spectra was analyzed using the PROSPECT model. The result showed that
      the bionic camouflage materials should be provided with coarse surface and spongy
      inner structure, the refractive index of main content must be close to that of
      plant leaves, the contents of materials should contain chlorophyll and water, and
      the content of C-H bond must be strictly controlled. Based on the analysis above,
      a novel camouflage material, which was constituted by coarse transparent
      waterproof surface, chlorophyll, water and spongy material, was designed. The
      result of verifiable experiment showed that the reflectance spectra of camouflage
      material exhibited the same characteristics as those of plant leaves. The
      similarity coefficient of reflectance spectrum of the camouflage material and
      camphor leaves was 0.988 1, and the characteristics of camouflage material did
      not change after sunlight treatment for three months. The bionic camouflage
      material, who exhibited a high spectral similarity with plant leaves and a good
      weather resistance, will be an available method for reconnaissance of
      hyperspectral imaging hopefully.

PMID- 21847956
TI  - [Analysis of mixed alkane gas based on Tikhonov regularization spectra selection
      and optimal neural network parameters selection].
AB  - Feature variable selection and modeling are two of the most principal research
      contents in spectral analysis. In the present paper, beginning from the
      introduction of feature spectrum selection based on Tikhonov regularization and
      discussion on it's application in multi-component mixed alkane gas analysis, 7
      sets of feature spectra were abstracted from the absorption spectra of 7 kinds of
      alkane gas, including methane, ethane, propane, iso-butane, n-butane, iso-pentane
      and n-pentane. In order to overcome the problem of over-training of neural
      network, a method called optimal parameter selection of neural netework (NN) was
      presented to build analysis model of analyte. Optimal parameters were selected
      from many trained networks with same architecture based on error process. And
      analysis models of spectral analysis for 7 kinds of alkane gas were built.
      Finally, the testing analysis results done with standard gases are given. The
      results show that the method presented in this paper can be used to reduce the
      cross--sensitivity between any two kinds of gas. The cross-sensitivity is less
      than 0.5%. The resolving power is as high as 20 X 10(-6).

PMID- 21847957
TI  - [A novel SMOreg algorithm based on instance cloned and its research on spectral
      modeling for hydromica in uranium deposit].
AB  - Hydromica is a typical alteration mineral in granite-type uranium deposit, and
      also an important indication of uranium. The amount of hydromica to some extent
      reflects the strength of hydromicasization in uranium deposit. Because of the bad
      performance of the traditional modelling methods in prediction, in the present
      paper, the authors' adopt SMOreg in the spectral modelling for hydromica, and
      validate its effectiveness. The authors' also propose a novel method called
      ICSMOreg. In this method the authors' employ instance cloned method to learn the
      samples selected by having a strong affinity with the test sets, and then get the
      new samples into SMOreg to build the spectral model. Finally, we experimentally
      compare ICSMOreg with SMOreg, artificial neural network, model tree and the
      common modelling methods like linear regression, multiple linear regression. The
      result shows that the new method improves the accuracy of prediction, and also
      reduces the negative impact of noise.

PMID- 21847958
TI  - [Study on the effect of solar spectra on the retrieval of atmospheric CO2
      concentration using high resolution absorption spectra].
AB  - Taking solar source as radiation in the near-infrared high-resolution absorption
      spectrum is widely used in remote sensing of atmospheric parameters. The present
      paper will take retrieval of the concentration of CO2 for example, and study the
      effect of solar spectra resolution. Retrieving concentrations of CO2 by using
      high resolution absorption spectra, a method which uses the program provided by
      AER to calculate the solar spectra at the top of atmosphere as radiation and
      combine with the HRATS (high resolution atmospheric transmission simulation) to
      simulate retrieving concentration of CO2. Numerical simulation shows that the
      accuracy of solar spectrum is important to retrieval, especially in the hyper
      resolution spectral retrieavl, and the error of retrieval concentration has poor
      linear relation with the resolution of observation, but there is a tendency that
      the decrease in the resolution requires low resolution of solar spectrum. In
      order to retrieve the concentration of CO2 of atmosphere, the authors' should
      take full advantage of high-resolution solar spectrum at the top of atmosphere.

PMID- 21847959
TI  - [Study of the over-fitting in building PLS model using orthogonal signal
      correction].
AB  - In the present paper, the over-fitting phenomenon in building PLS model using
      orthogonal signal correction (OSC) was studied through establishment of
      quantitative calibration models for the peanut oil content in blending edible
      oils, and for the dimethylsulfoxide concentration in water solution. The cross
      validation results and the predication results of PLS models using OSC and
      without using OSC were compared to evaluate the effectiveness of OSC for
      improving the performance of PLS1 model. The results show that the application of
      OSC to PLS modeling will lead to an over-fitting phenomenon. According to the
      principles of their algorithms, when OSC and PLS are used together, the signals
      which are not correlated to the interested property are removed twice from the
      raw spectra. This leads to deleting the parts of useful information in spectra,
      and to spoiling the predictive ability of PLS models to some extent.

PMID- 21847960
TI  - [The research on active constituent distribution of rhizoma coptidis pieces].
AB  - In order to test the distribution of active constituent of traditional Chinese
      medicine and to evaluate the quality of medicinal part effectively, spectral
      imaging analysis technology was used, and rhizoma coptidis pieces were tested as
      an example. First, the fluorescence spectral cube was taken, and the spectral
      curve of 3 different medicinal parts of the piece was obtained; second, spectral
      images were reconstructed by principal components analysis method, and the
      differences of 3 medicinal parts on the first few principal components were
      focused; third, the first component image was divided by the threshold method,
      then the distribution and relative content of 3 medicinal parts were obtained.
      The results show that spectral imaging analysis technology can provide the
      distribution of the active constituent, which can be used as the criterion of
      selecting medicinal parts. The testing course is nondestructive and rapid.

PMID- 21847961
TI  - [Experimental investigation of quantitatively analysing trace Mo in complex
      metallic alloys by laser induced breakdown spectroscopy].
AB  - The quantitative analysis using laser induced breakdown spectroscopy (LIBS), lack
      of appropriate interior label element, is described and applied to trace element
      molybdenum (Mo) detection in complex metallic alloys. A Q-switched Nd : YAG laser
      operating at 532 nm was utilized to generate plasma and the emission was recorded
      by a grating spectrometer equipped with CCD, boxcar and PMT. The three peak
      heights of Mo I , 550.649, 553.305 and 557.045 nm, changing with Mo mass fraction
      in metallic alloys were measured to produce calibration curves respectively, and
      double blind method was used to analyse a test sample. Based on Mo I 550.649 nm
      line, the Mo mass fraction in the test sample was determined to be 2.229% with
      relative error of 5.57% in comparison with the given value of 2.111%. On using Mo
      I 557.045 nm line, the relative error was found to be doubled due to the overlap
      with Fe emission lines. While taking the total height of three atomic lines into
      account in analysis, the resulted error dropped to 7.58%, even better than the
      average of predicted concentrations based on the above three lines. The obtained
      results demonstrate that satisfactory precision could be obtained under a
      consistent experiment condition with the above scheme, even without appropriate
      interior label element. The methods of maintaining stable laser ablation
      efficiency on sample are also discussed.

PMID- 21847962
TI  - [Preparation of Pb2+ imprinted acrylic acid-co-styrene and analysis of its
      adsorption properties by FAAS].
AB  - With lead ion template, acrylic acid as functional monomer, potassium persulfate
      as initiator, strytrene as framework monomer, lead ion imprinted polymers (Pb(II)
      IIPs) were prepared using free emulsion polymerization method. The structure and
      morphology of the polymers were analyzed by UV-spectra, FTIR and scanning
      electron microscopy. The adsorption/ desorption and selectivity for Pb2+ were
      investigated by flame atomic absorption spectrometry (FAAS) as the detection
      means. The results show that compared with non-imprinted polymers(NIPs), the
      Pb(II)-IIPs had higher specific adsorption properties and selective recognition
      ability for Pb(II). The relative selectivity coefficient of Pb(II)-IIPs for
      Pb(II) was 6.25, 6.18, 6.25 and 6.38 in the presence of Cd(II), Cu(II), Mn(II)
      and Zn(II) interferences, respectively. The absorption rate was the best at the
      pH of adsorbent solution of 6, Adsorption rate reached 96% during the 2.5 h
      static adsorption time. Using 3.0 mol x L(-1) HCI as the best desorption solvent
      to desorb the adsorbents, the desorbtion rate reached 98%. Under the best
      adsorption conditions, the adsorption capacity of Pb(II)-IIPs for Pb(II) was
      found to be 40. mg x g(-1).

PMID- 21847963
TI  - [The evaluation of uncertainty in the results for elements rubidium, strontium,
      yttrium and zirconium in silicate geological samples by polarized energy
      dispersive X-ray fluorescence spectrometry].
AB  - A method for evaluation of uncertainty was established with standard deviation of
      relative error. Utilizing a polarized energy dispersive X ray fluorescence
      spectrometer (P-EDXRF)X-lab 2000 with pressed polyethylene-backed pellets, 76
      national reference materials and 89 geological examination samples were analyzed,
      the results indicated that the relative errors consist with the normal
      distribution with confidence level 95%. The section standard deviations of
      relative errors acted as method global relative uncertainty and expanded factor
      was 2. The section relative uncertainty caused by precision was analyzed and
      relative uncertainty caused by accuracy based on the error transfer formula was
      isolated. The ratio of relative uncertainty caused by accuracy to the global
      relative uncertainty was different with different levels and elements. Two
      methods validated that the evaluation of global uncertainty is reasonable, with
      the first method being the formula of audited results in laboratory, and the
      second being the comparison of standard value with expanded uncertainty and a
      revised value with expanded uncertainty.

PMID- 21847964
TI  - [Boundary threshold value method used in crystalline material internal defect
      detection by short wavelength X-ray diffraction].
AB  - There are few references about crystalline material internal defect detected by X
      ray diffraction tomography using common X-ray source. Short wavelength X-ray
      diffractometer (SWXRD), invented by Institute of Southwest Technology
      Engineering, is a relatively small and inexpensive instrument compared to
      synchrotron radiation or neutron reactor. Boundary determination of defect
      affects the imaging quality and the distinguishing of defect in X-ray diffraction
      tomography using SWXRD. In the present paper, threshold value method of
      diffracted intensity is put forward to process the test data, so the boundary of
      defect is legible. In order to study how the factors influence the threshold
      value, Gauss function is used in fitting the test data. The influence of
      varisized image quality indicator pressed in powdered aluminum on threshold value
      has been studied. The result shows that 91% of the diffraction intensity of
      substrate can be regarded as the threshold value. The experiment of slit in
      aluminum alloy sheet further verified the threshold value method. It's useful in
      detecting the defect boundary.

PMID- 21847965
TI  - [Study on bamboo treated with gamma rays by X-ray diffraction].
AB  - The microfibril angle and crystallinity of bamboo treated with gamma rays were
      tested by X-ray diffraction (XRD). The result indicated that crystallinity in
      bamboo increased when irradiation dose was less than 100 kGy, while the
      irradiation dose was raised to about 100 kGy, crystallinity in bamboo reduced.
      But during the whole irradiation process, the influence on microfibril angle was
      not obvious, so it was not the dominant factors on variation in physical
      mechanical properties of bamboo during the process of irradiation.

PMID- 21847966
TI  - [Energy response of Tb(3+)-doped silicate scintillating glass to hard X-ray].
AB  - Tb(3+)-doped silicate scintillating glass was made by high temperature melt
      quenching method and the energy response to hard X-ray (from 5 to 80 keV) was
      measured. The response of photocurrent of silicate scintillating glass to X-ray
      (with various energy) is nonlinear. It was noted that the change in nonlinearity
      around 8 and 50 keV is obvious. This phenomenon is concerned with the production
      of abundant electrons when the scintillating glass absorbed X-ray and the energy
      response of scintillating glass to electrons.

PMID- 21847967
TI  - [Influence of extended light source on spectral reconstruction in a micro FTIR].
AB  - The influence of extended light source on spectral reconstruction in the FTIR
      (fourier transform infrared spectrometer) based on step mirrors was discussed in
      the present paper. The relationship between coherent intensity and solid angle
      was calculated. It was found that the coherent length became shorter and the
      spectrum resolving power became lower as a result of solid angle produced by the
      extended light source. The spectrum resolving power of system could reach the
      value as the theoretic design if the solid angle of extended light source is
      smaller than 0.001. The radiance will reduce if the size of extended light source
      is shortened. Therefore, a suitable size of extended light source can be chosen,
      considering the requirement of SNR in the optical design.

PMID- 21847968
TI  - [Advance of stir bar sorptive extraction].
AB  - Stir bar sorptive extraction (SBSE) is an environmentally-friendly technology of
      sample preparation which combines extraction, cleanup and enrichment together,
      and it has been developed rapidly and widely applied to the trace enrichment of
      various target analytes in environmental, food and biological samples. Based on
      our research, the advance of SBSE, especially, the development of new coatings,
      are reviewed. At the same time, the possible development orientations of SBSE are
      discussed.

PMID- 21847969
TI  - Sequential extraction leading to improved proteomic analysis of the oleaginous
      yeast Lipomyces starkeyi.
AB  - The oleaginous yeast Lipomyces starkeyi (L. starkeyi) is an excellent
      intracellular lipid producer. Thus, extraction of protein from lipid-rich L.
      starkeyi samples following conventional methods can be difficult, leading to poor
      data in terms of proteomic analysis. The presence of lipophilic components in
      those samples may also interfere with the extraction process and the downstream
      analysis. In this work, we developed a sequential extraction method for
      preparation and analysis of L. starkeyi proteome combining to an online
      multidimensional nano reversed-phase liquid chromatography-tandem mass
      spectrometry (microRPLC-MS/MS) strategy. Protein hits of high confidence reached
      227 with false positive rate less than 0.1, twice of those identified from the
      one-buffer extraction preparation. Moreover, the protein hits related to primary
      metabolism was increased, which may be important to establish the molecular
      mechanism of lipid accumulation. The method should be valuable for protein
      extraction from oleaginous species.

PMID- 21847970
TI  - [Comparison of intracorporal absorption of hypaconitine in Heishunpian decoction
      and its compound recipe decoction by ultra performance liquid chromatography
      quadrupole time-of-flight mass spectrometry].
AB  - An ultra performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry (UPLC/Q-TOF MS) method was developed for the determination of
      hypaconitine in the plasma of the rats administered with Heishunpian (HSP)
      decoction, Zhufu (ZF) decoction and Gancaofuzi (GF) decoction, separately.
      Hypaconitine and the internal standard were separated on a ZORBAX Extend-C18
      column. The concentration-time curve of hypaconitine in the plasma was
      protracted, and pharmacokinetic parameters were calculated, then the
      pharmacokinetic comparison of hypaconitine between HSP, ZF and GF was carried out
      for the first time. The results of the methodological test showed that the plasma
      concentration of hypaconitine presented good linear relationship in the range of
      0.02-10 ng/mL. The results of the sample determination showed that the absorptive
      degree of nfrom ZF decoction in the plasma was lower than that from HSP
      decoction, while the absorptive degree of hypaconitine from GF decoction in
      plasma was higher than that from HSP decoction. It was deduced that some
      components in ZF decoction can restrain the absorption of hypaconitine in plasma,
      and some components in GF decoction may promote the absorption of hypaconitine in
      plasma, and the difference in drug effects between ZF decoction and GF decoction
      may derive from the different absorptive degrees of hypaconitine in plasma. The
      pharmacokinetic property of hypaconitine was proposed to be non-linear dynamics
      on the basis of the drug elimination half life (T(1/2)) and the area under the
      plasma concentration-time curve (AUC).

PMID- 21847971
TI  - [Simultaneous determination of 7 arsenic species in chicken muscle and chicken
      liver with high performance liquid chromatography-inductively coupled plasma mass
      spectrometry].
AB  - A method for the simultaneous determination of 7 arsenic species was developed
      with high performance liquid chromatography and inductively coupled plasma mass
      spectrometry (HPLC-ICP-MS). The sample was extracted with artificial gastric
      juice. The HPLC separation was performed on an anion analytical column utilizing
      a gradient elution program of ammonium carbonate and water as the mobile phase.
      Identification and quantification were achieved by ICP-MS. Good linearities of 7
      arsenic species were observed in the range from 1 microg/kg to 50 microg/kg with
      the correlation coefficients greater than 0.999. The average recoveries of 7
      arsenic species spiked at the three levels of 1, 2 and 10 microg/kg ranged from
      84.3% to 106.6% with the relative standard deviations of 1.4%-4.2%. The
      quantification limits of 7 arsenic species were 1 microg/kg. The method was
      proved to be good reproducibility, high sensitivity and simple preprocessing.
      This method is suitable for the simultaneous determination of 7 arsenic species
      in chicken muscle and chicken liver.

PMID- 21847972
TI  - [Determination of bisphenol A in milk by liquid chromatography-tandem mass
      spectrometry coupled with solid phase extraction of monodisperse magnetic
      submicron particles as adsorbent].
AB  - Monodisperse magnetic submicron particles were synthesized by a solvothermal
      reduction method. A solid phase extraction (SPE) based on the monodisperse
      magnetic submicron particles and high performance liquid chromatography-tandem
      mass spectrometry (HPLC-MS/MS) method for the determination of bisphenol A (BPA)
      at trace level in milk has been established. The important parameters that affect
      the extraction efficiency such as the solution pH, dosage of magnetic submicron
      particles, nature of elution solution and its volume were optimized. The optimal
      extraction conditions were as follows: the pH 6.0, the dosage of 3.5 mg magnetic
      submicron particles and 0.4 mL methanol as elution solution. BPA was analyzed by
      HPLC-MS/MS in negative ion mode using an Agilent XDB C18 column as analytical
      column. Under the optimal conditions, the calibration curves showed a good
      linearity in the BPA concentration range of 1.0-100.0 micro g/L. The correlation
      coefficient was 0. 999 3. The average recoveries of BPA at three spiked levels
      ranged from 85.3% to 96. 1% with the relative standard deviations (RSDs) less
      than 10%. The detection limit of the method was 1.0 microg/L. The method is
      sensitive, simple, and suitable for the rapid determination of BPA in milk.

PMID- 21847973
TI  - [Quantification of acrylamide in foods by gas chromatography-mass spectrometry
      coupled with pro-column derivatization].
AB  - The quantification of acrylamide in foods was investigated by gas chromatography
      mass spectrometry (GC-MS). In this method, (13)C3-acrylamide was used as an
      internal standard. The samples were homogenized, defatted with hexane and
      extracted with ethyl acetate for twice. The derivatization of acrylamide into 2
      bromopropenamide (2-BPA) was done using potassium bromide/potassium bromate at 4
      degrees C for 90 min. Selective ion monitoring mode was chosen to monitor
      objective chromatography. This method had a good linearity between 0.05-2.00
      mg/kg (r2 = 0.9995), and the limits of detection and quantification were 3
      microg/kg and 7 microg/kg, respectively. The recoveries of acrylamide were in the
      range of 62.7%-65.5%. In order to confirm this GC-MS method, the acrylamide in
      foods was also determined by high performance liquid chromatography coupled to
      quadrupole tandem mass spectrometry (HPLC-MS/MS), which had been proved in our
      laboratory. The concentrations of acrylamide in the samples quantified by GC-MS
      were slightly higher than those detected by HPLC-MS/MS. This method can be used
      to quantify acrylamide in normal foods.

PMID- 21847974
TI  - [Determination of 88 pesticide residues in tea using gas chromatography-tandem
      mass spectrometry].
AB  - A multi-residue method for the determination of 88 pesticides in tea using gas
      chromatography-tandem mass spectrometry (GC-MS/MS) was developed. The target
      compounds were extracted with acetonitrile by accelerated solvent extraction
      (ASE), and the extracts were cleaned up by solid phase extraction (SPE) with a
      Carbon/NH2 cartridge and eluted with acetonitrile-toluene (3:1, v/v) before the
      identification and quantification of the residues by GC-MS/MS. Performance
      characteristics, such as accuracy, precision, linear range, limits of detection
      (LODs) and limits of quantification (LOQs), for each pesticide were determined.
      At low concentration level spiked (6.4 microg/kg), the average recoveries were in
      the range of 70%-100% for 87.5% analytes and the relative standard deviations
      (RSDs) were lower than 15% for 87.5% analytes. The quantification of analytes was
      carried out using the most sensitive transition for every compound and by matrix
      matched standards calibration. The LOQs (S/N = 10) were less than 10 microg/kg
      for 86.4% analytes. The method is sensitive, accurate, reliable and suitable for
      the simultaneous determination of multi-residue pesticides in green tea, Woolong
      tea, black tea and Puer tea.

PMID- 21847975
TI  - [Determination of photoinitiators in printing inks used in food contact
      materials].
AB  - A new analytical method based on gas chromatography-mass spectrometry (GC-MS)
      techniques was developed for the determination of five photoinitiators (PIs),
      benzophenone (BP), 4-methylbenzophenone (MBP), ethyl-4-dimethylaminobenzoate
      (EDAB), 2-ethylhexyl-4-dimethylaminobenzoate (EHDAB) and 1-hydroxycyclohexyl
      phenyl ketone (Irgacure 184), in the printing inks used in food contact
      materials. The test solutions were extracted from selected food contact materials
      using Soxhlet extractor with ethyl acetate as the extraction solvent. By adding
      50 and 200 microg/L of a standard mixture of photoinitiators into the extracts of
      the blank packaging materials, the recoveries obtained were in the range of 66.7%
      89.4%. The repeatability of the method was assessed by determining the contents
      of the photoinitiators in five types of food contact materials, and the results
      were lower than 10%. The instrumental detection limits (IDLs) and method
      quantification limits (MQLs) were in the range of 2.9-6.0 microg/L and 0.0017
      0.0036 mg/dm2, respectively. The method was applied in the analysis of about
      twenty real samples (yogurt carton, milk carton, fruit juice carton and plastic
      bags samples). The most significant pollutants were BP and MBP. The
      concentrations of Irgacure 184, EDAB and EHDAB found in three individual samples
      were 0.84 mg/dm2, 0.2 mg/dm2 and 1.2 mg/dm2, respectively. The work proposed a
      new method to analyze the migration level of initiators from the inks.

PMID- 21847976
TI  - [Determination of primary aromatic amines in crayons gas chromatography-mass
      spectrometry].
AB  - A method for the determination of nine primary aromatic amines in crayon by solid
      phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) was
      developed. The alkanes in the sample were removed with n-hexane. Then the sample
      was extracted twice with ultrasonic extraction by methanol. The extract was
      evaporated, then the concentrated solution reacted with the reducing agent
      (sodium hydrosulfite) for 30 min at 70 degrees C. After the extraction with a
      diatomite SPE column, the aromatic amines were collected and separated on an HP
      5M column, determined by MS. The nine primary aromatic amines can be separated
      and determined successfully. Under the optimized conditions, the detection limits
      were 5 mg/kg and the spiked recoveries of the samples were in the range of 86.02%
      102.43%. The method is accurate and stable. It can be applied in the analysis of
      the primary aromatic amine of real crayon samples.

PMID- 21847977
TI  - [Preparation and evaluation of silica xerogel monolithic column].
AB  - Using potassium silicate as silicon source, formamide as catalyst, a series of
      silica xerogel monolithic columns with different consistencies were prepared. The
      column bed would not rupture and collapse during drying at high temperatures.
      This is the biggest advantage compared with the inorganic monolithic columns
      using alkoxy silane as precursor. The effect of the modulus of potassium silicate
      on the physical structure of the monolithic column was investigated. The
      monolithic silica columns were characterized by scanning electron micrograph
      (SEM) and nitrogen adsorption. The relationship between column pressure and flow
      rate was evaluated. The column efficiency for anthracene was tested. The
      breakthrough curve for toluene was studied. The results showed that the column
      bed could maintain good stability at high temperatures, high column pressures,
      and high flow rates. The column efficiency of 41,400 plates/m was achieved for
      anthracene. The column capacity for toluene was 61 ng.

PMID- 21847979
TI  - [Simultaneous determination of tryptophan and its key metabolites by high
      performance liquid chromatography with programmed wavelength ultraviolet
      detection].
AB  - A high performance liquid chromatographic (HPLC) method with programmed
      wavelength ultraviolet (UV) detection was established to simultaneously determine
      tryptophan (Trp) and its key metabolites kynurenine (Kyn) and 5-hydroxytryptamine
      (5-HT). A BDS-Hypersil-C8 column (150 mm x 4.6 mm, 5 microm) was used for the
      analysis at 25 degrees C. The separation was carried out with the mobile phase
      consisting of 10 mmol/L sodium acetate-acetic acid (pH 4. 5) and acetonitrile
      (94: 6, v/v) using theophylline as internal standard (IS) at a flow rate of 0.6
      mL/min. The eluates were monitored by the programmed wavelength UV detection at
      360 nm for Kyn and IS, 220 nm for 5-HT and 302 nm for Trp. The mean recoveries
      were in the range of 87% to 113%. The linearities were from 3.97 to 400
      micromol/L for Trp, 0.421 to 20.2 micromol/L for Kyn and 4.36 to 980.5 nmol/L for
      5-HT. The detection limits were 0.134 micromol/L for Trp, 0.016 micromol/L for
      Kyn and 2.03 nmol/L for 5-HT. Fifteen plasma samples of patients with depression
      and fifteen plasma samples of healthy controls were tested, and the results
      demonstrated that the metabolism of Trp in the plasma from the depression group
      was significantly different from that of the control group.

PMID- 21847978
TI  - [Isolation and structure identification of C19 diterpenoid alkaloids from
      Aconitum carmichaeli by high-speed counter-current chromatography].
AB  - Three C19 diterpenoid alkaloids were isolated and purified from the lateral roots
      of Aconitum carmichaeli Debx. (Fuzi in Chinese) by high-speed counter-current
      chromatography (HSCCC). A mixture of n-hexane-ethyl acetate-methanol-water
      (3:5:4:5, v/v/v/v) was used as the two phase solvent system. The lower phase was
      used as the mobile phase and was operated at a flow rate of 2.0 mL/min, while the
      apparatus was rotated at 850 r/min, and the detection wavelength was at 235 nm.
      Under these conditions, 15.3 mg of beiwutine, 35.1 mg of mesaconitine and 22.7 mg
      of hypaconitine were obtained from 90 mg of crude extract in one-step separation
      with the purities of 97.9%, 96.2% and 99.2%, respectively, determined by high
      performance liquid chromatography. The structures of these three compounds were
      identified by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear
      magnetic resonance (1H-NMR) and 13C-NMR. The results indicate that HSCCC is a
      powerful technique for the purification of diterpenoid alkaloids from the lateral
      roots of Aconitum carmichaeli Debx.

PMID- 21847980
TI  - [Simultaneous determination of 6 phenolic acids in coffee beans by reversed-phase
      high performance liquid chromatography].
AB  - A method of reversed-phase high performance liquid chromatography coupled with
      diode array detection (HPLC-DAD) was established for the simultaneous
      determination of 6 phenolic acids in green coffee beans. These phenolic acids are
      caffeic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O
      caffeoylquinic acid, 3,5-O-dicaffeoylquinic acid and 4,5-O-dicaffeoylquinic acid.
      The separation was achieved using a Kromasil C18 column (200 mm x 4.6 mm, 5
      microm) under the gradient elution with the mobile phases of acetonitrile and
      0.1% (v/v) formic acid/water. The 6 phenolic acids were well separated within 45
      min. The recoveries were from 90.76% to 104.73% with the relative standard
      deviations between 0.7% and 3.9%. The method is simple, rapid and highly
      sensitive, suitable for the simultaneous determination of 6 phenolic acids and
      quality control of coffee beans.

PMID- 21847981
TI  - [Analysis of organochlorine pesticides and pyrethroid pesticides in vegetables by
      gas chromatography-electron capture detection coupled with solid-phase extraction
      using multiwalled carbon nanotubes as adsorbent].
AB  - A multi-residue analytical method based on solid-phase extraction (SPE) with
      multiwalled carbon nanotubes (MWCNTs) as adsorbent was developed. The
      determination of 6 organochlorine pesticides and 7 pyrethroid pesticides in
      vegetables (including cucumber, cherry tomato, cabbage, lettuce, purple cabbage,
      leek, shallot and onion) was carried out by gas chromatography-electron capture
      detection (GC-ECD). The GC-ECD method used two columns (HP-50 and HP-1) and two
      ECD detectors. The HP-50 column was used for the analysis and the HP-1 column for
      validation. The clean-up conditions were optimized. The analytes were extracted
      by acetonitrile, and the extract was cleaned up by the MWCNTs SPE cartridge. The
      extract was re-dissolved by hexane, eluted with acetone-hexane (7:3, v/v) from
      the columns. The recoveries were over 70% for the 11 pesticides in the 13
      pesticides. The results indicated that the MWCNTs SPE cartridge was efficient for
      8 vegetable samples, because it reduced the contamination of the coloring
      materials to GC-ECD. The experimental results showed the MWCNTs SPE cartridge can
      adsorb the coloring materials and the eluant was nearly colorless.

PMID- 21847982
TI  - [Determination of nitroimidazoles in oral hygiene by ultra-performance liquid
      chromatography-tandem mass spectrometry].
AB  - A method for the simultaneous determination of metronidazole, tinidazole,
      ornidazole, ronidazole and dimetridazole in oral hygiene by ultra-performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed.
      The sample was diluted with 0.1% formic acid/acetonitrile (95:5, v/v), then
      centrifuged and filtered with a membrane. The separation was carried out on a
      Cloversil C18 column (100 mm x 2.1 mm, 3.5 microm) with the gradient elution of
      0.1% formic acid and acetonitrile as the mobile phases. The analytes were
      determined by UPLC-MS/MS and quantified by external standard method. The
      calibration curves showed good linearity in the range of 1.0-60.0 microg/L with r
      > or = 0.9992. The recoveries were 91.5%-108% at the three spiked levels of 10.0,
      20.0 and 100 mg/kg, and the relative standard deviations were 1.14%-5.22%. This
      method is easy, sensitive and suitable for the determination of nitroimidazoles
      in oral hygiene.

PMID- 21847983
TI  - [Determination of imperatorin and isoimperatorin in cosmetics by high performance
      liquid chromatography-tandem mass spectrometry].
AB  - A novel method for the simultaneous determination of imperatorin and
      isoimperatorin in cosmetics by high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) was developed. The imperatorin and isoimperatorin were
      extracted by methanol. The analytes were separated on a C18 column using 10
      mmol/L ammonium acetate/ methanol-5 mmol/L ammonium acetate aqueous solution
      (80:20, v/v) as mobile phase, and then detected by HPLC-MS/MS using multiple
      reaction monitoring (MRM) mode. The good linearities (r > 0.999) were achieved
      for the target compounds over the range of 0.25-20 microg/L. The limits of
      quantification (LOQs) were 0.5 mg/kg. The recoveries for the imperatorin and
      isoimperatorin varied from 82.2% to 105% and 80.0% to 103% with the relative
      standard deviations ranging from 2.7% to 4.9% and 1.8% to 4.6% respectively in
      the range of 0.50-10.0 mg/kg. The method can meet the requirements for the
      simultaneous determination of imperatorin and isoimperatorin in cosmetics.

PMID- 21847984
TI  - [Simultaneous determination of 3 benzalkonium chloride homologs in cosmetics by
      high performance liquid chromatography].
AB  - An analytical method based on high performance liquid chromatography with a diode
      array detector (HPLC-DAD) has been established for the simultaneous determination
      of 3 benzalkonium chloride homologs (n-C12H25-C9H13NCl, n-C14H29-C9H13NCl, n
      C16,H33-C9H13NCl) in cosmetics. The sample was extracted with methanol (including
      0.5% formic acid) under ultrasonic operation, the HPLC separation was carried out
      on a CAPCELL PAK SCX column (250 mm x 4.6 mm, 5 microm), the mobile phases were
      40 mmol/L ammonium acetate solution (including 0.1% triethylamine) and
      acetonitrile with gradient elution, the flow rate was 1.0 mL/min, the detection
      wavelength was 260 nm, the column temperature was 25 degrees C, and the injection
      volume was 20 microL. The limit of detection was 50.0 mg/kg and the quantitation
      limit was 200.0 mg/kg for 3 benzalkonium chloride homologs in cosmetics. The
      linear plots were obtained between 5.0 mg/L and 3000.0 mg/L. Overall recoveries
      were between 92.5% and 102.1% with the relative standard deviations (RSDs)
      between 3.81% and 6.66%. The method is simple, rapid, accurate and suitable for
      the determination of 3 benzalkonium chloride homologs in cosmetics.

PMID- 21847985
TI  - [Characterization of surface properties of polybutadiene rubber by inverse gas
      chromatography].
AB  - Inverse gas chromatography was applied to the characterization of the surface
      properties of polybutadiene rubber (PBR). Four n-alkanes (C6, C7, C8 and C9
      alkanes) were chosen as the apolar probes to characterize the dispersive
      component of surface free energy. Dichloromethane, trichloromethane, acetone,
      ethyl acetate, diethylether and tetrahydrofuran were chosen as the polar probes
      to detect the Lewis acid-base parameters. It was found that the dispersive
      components of surface free energy were 47.07, 46.46, 45.85, 45.60 and 45.09 mJ/m2
      at 303, 313, 323, 333 and 343 K, respectively. The results showed that the
      surface free energy decreased linearly with the increase of temperature. The
      Lewise acidic number Ka of PBR was 0.34, and the basic number Kb was 1.77. The
      fact Kb/Ka >1 means that the surface of PBR was amphoteric with dominant basic
      character and the total ability of the surface to acid-base interactions was
      2.11. The free energies of adsorption -deltaG(a)s and -deltaH(a)s by Lewis acid
      base interaction were also figured out.

PMID- 21847986
TI  - [Capsid assembly and DNA encapsidation of adeno-associated virus].
AB  - Recombinant adeno-associated viral vectors (rAAV) have been widely used as gene
      therapy vectors in clinical trials. Here, we reviewed the genomic structures and
      replication mechanisms of wt-AAV. Then, the assembly of capsid and the
      encapsidation of genomic DNA, two major events during AAV pakaging, was discussed
      in detail. Although the overall pattern of virus assembly and encapsidation is
      known, the molecular mechanisms and the structure-function relationship involved
      in these processes are not well understood. Further elucidatation of these
      processes may improve the production technology of rAAV and develop gene drug
      based on rAAV.

PMID- 21847987
TI  - [Applications and perspectives of DNA stable-isotope probing in metagenomics: a
      review].
AB  - DNA stable-isotope probing (DNA-SIP) is a recently developed method with which
      the incorporation of stable isotope from a labeled substrate is used to identify
      the function of microorganisms in the environment. The technique has now been
      used in conjunction with metagenomics to establish links between microbial
      identity and particular metabolic functions. The combination of DNA-SIP and
      metagenomics not only permits the detection of rare low-abundance species from
      metagenomic libraries but also facilitates the detection of novel enzymes and
      bioactive compounds. We summarize recent progress in SIP-metagenomic techniques
      and applications and discuss prospects for this combined approach in
      environmental microbiology and biotechnology.

PMID- 21847989
TI  - [Screening proteins interacting with infectious bursa disease virus Gt VP2 from
      cDNA library of B lymphoid cells of the bursa of Fabricius].
AB  - To screen the interactive proteins with IBDV Gt VP2 protein from cDNA library of
      B Lymphoid cells of the bursa of Fabricius. The expression cDNA library plasmids
      was transformed to the yeast competent cells, which have the bait plasmid-Gt VP2.
      After testing for growth in synthetic complete medium lacking histidine and
      uracil and for production of beta-galactosidase (X-gal), we obtained 16 positive
      clones. We searched the gene sequences of positive clones in the NCBI website.
      The blast results showed that five positive clones were the gallus sequences.
      They were Gallus gallus breed mitochondrial DNA, O_G1cNAc transferase, Tumor
      protein p53 binding protein, Stathmin and Chondroitin sulfate Ga1NAcT-2,
      respectively. This study is helpful for the further identifying the receptors of
      IBDV in B Lymphoid cells of the bursa of Fabricius.

PMID- 21847988
TI  - [Structure and function of tonoplast Cation/H+ antiporters in plant: a review].
AB  - Cation transporters play important roles in modulating the concentration of
      intracellular metal ions. The vacuole is an important storage organelle for many
      ions. Cation (Ca+)/H+ antiporters (CAXs) located at vacuolar membrane are mainly
      involved in the Ca2+ flux into the vacuole, and appear to be capable of
      transporting various divalent cations to some degree. Several CAX genes have been
      isolated and characterized from various plants in recent years. Four domains of
      plant CAXs have been identified: NRR regulates Ca2+ transport by a mechanism of N
      terminal autoinhibition; Ca domain and C domain confer Ca2+ and Mn2+ specificity
      among CAX transporters, respectively; D domain plays a part in the regulation of
      cytosolic pH. AtCAXs identified in Arabidopsis thaliana are involved in the
      growth, development and stress adaption of plant. AtCAX3 is the mainly Ca2+/H+
      transporter in response to salt stress; AtCAX2 and AtCAX4 participate in
      transportation and detoxicification of heavy metal ions (Cd2+, Zn2+, and Mn2+) in
      cells under heavy metal stress, and impact root/shoot Cd partitioning in plant.
      These suggest that CAX genes may be useful for nutritional enhancement of plants,
      and for increasing phytoremediation potential. Here, the classification,
      structure and function of CAXs in plants are reviewed.

PMID- 21847990
TI  - [Cloning and expression of Staphylococcus aureus surface protein Isdb and its
      immune experiment in mice].
AB  - In order to characterize the immunogenicity and immunoprotection of the
      Staphylococcus aureus (S. aureus) surface Isdb, we amplified Isdb gene from S.
      aureus Wood46 strain. The isdb gene was subsequently inserted into pET32a(+)
      vector and the recombinant plasmid was transformed into E. coli strain BL21. The
      recombinant Isdb was expressed and purified. Then, we immunized mice with the
      purified recombinant protein. The antibody level was measured by enzyme-linked
      immunosorbent assay. Finally, immunized mice were challenged with S. aureus
      strains Wood46 and HLJ23-1. These results showed that isdb gene sequences were
      highly conserved, and the recombinant Isdb was successfully expressed. The
      antibody titer in the immunized groups was increased significantly (P < 0.05)
      compared with the control, the protective rate of Isdb protein inducted by
      challenge with the two S. aureus stains Wood46 and HLJ23-1 was 62.5% and 75%,
      respectively. These results showed that the Isdb protein had high immunogenicity
      and immunoprotective capacity.

PMID- 21847991
TI  - [Construction of Saccharomyces cerevisiae mutant with knockout of SNF4 gene].
AB  - Construction and ethanol production effects of SNF4 gene knockout in
      Saccharomyces cerevisiae were described in this paper. For knockout of SNF4 gene
      in S. cerevisiae YS2, a PCR-amplified disruption cassette was used, encoding the
      short flanking homologous regions to the SNF4 gene and Kan(r) as selectable
      marker. The SNF4 gene disruption cassette was transformed into S. cerevisiae YS2
      through LiAc/SS Carrier DNA/PEG. The positive transformants were grown on G418
      plates and verified by PCR. The Kan(r) marker was rescued by transforming plasmid
      pSH65 into positive transformants and inducing expression of Cre recombinase in
      galactose-containing medium. Lastly, the YS2-deltaSNF4 strain, in which SNF4
      allele gene were completely knocked out, was obtained by repeating the same
      procedure. The result of anaerobic fermentation showed that ethanol production of
      the SNF4 gene knockout strain had increased by 7.57 percent as compared with the
      original strain YS2. The experiment indicated ethanol production could be
      improved significantly with the approach ofSNF4 gene knockout by Cre-LoxP system.

PMID- 21847992
TI  - [Asymmetric synthesis of atorvastatin intermediate by Pichia pastoris X-33].
AB  - Ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate is a potential
      intermediate for the synthesis of HMG-CoA reductase inhibitor (atorvastatin) that
      can lower the cholesterol level in human blood. In this study, in order to
      synthesize ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate by
      bioreduction, the yeast strains in our lab were screened. Ethyl (R)-3-hydroxy-5
      (1,3-dioxoisoindolin-2-yl)-pentanoate was found to be produced efficiently from
      ethyl 5-(1,3-dioxoisoindolin-2-yl)-3-oxopentanoate by Pichia pastoris X-33. The
      effects of initial substrate concentration, reaction time, co-substrate, amount
      of yeast cells, pH, as well as the temperature on the yield and enantiomeric
      excesses (e.e. value) of product were examined in mono-phase system. The optimal
      reaction conditions are as fallows: substrate concentration 7 g/L, cell
      concentration 120 g/L, glucose concentration 120 g/L, pH 6.5, temperature 35
      degrees C, reaction time 12 h, and the yield 93.12% with the high e.e. value of
      98.55%.

PMID- 21847994
TI  - [Kinetics of enzymatic hydrolysis of steam-explosion pretreated corn straw].
AB  - In order to learn the enzymatic hydrolysis characteristics of steam-explosion
      pretreated corn straw by cellulase, the effects of substrate concentration,
      cellulase concentration and temperature were determined. The kinetics of the
      hydrolysis reaction could be described with the Michealis-Menten equation, and
      the hydrolysis reaction obeyed the classical first-order reaction rate in the
      first three hours. In the condition of 45 degrees C and pH 5.0 and the stirring
      rate 120 r/min, the Michealis constant (Km) and maximum rate (Vm) for 1.2 FPU/mL
      of cellulase were 11.71 g/L and 1.5 g/(L x h). The kinetic model, including the
      parameters such as substrate concentration, enzymatic concentration and
      temperature, was suit for the hydrolysis reaction under the temperature range
      from 30 degrees C-50 degrees C.

PMID- 21847993
TI  - [Rapid and high throughput measurement of lipase thermo-stability through ANS
      fluorescence signal assay].
AB  - We have developed a rapid and high throughput lipase-ANS (8-Anilino-l
      naphthalenesulfonic acid) assay to evaluate the thermo-stability of lipases based
      on the ANS fluorescence signal's increasing and shifting when this small
      fluorescence probes binds to lipase. The testing lipase samples were incubated at
      a temperature range of 25 degrees C to 65 degrees C for 30 min before mixed with
      ANS solution (0.20 mg/mL lipase and 0.05 mmol/L ANS in the buffer of 20 mmol/L
      Tris-HCl, 100 mmol/L NaCl, pH 7.2) in a cuvette or microplate. Fluorescence
      signals of the samples were measured at EX 378 nm, EM 465 nm with a fluorescence
      photometer or a plate reader, and Tm was calculated with the software of GraphPad
      Prism5.0. The Tm values of several mutants of Penicillium expansum lipase (PEL)
      were measured with this ANS assay and conventional method simultaneously and the
      results show that Tm values are comparative and consistent between these methods,
      suggesting that the lipase-ANS assay is a reliable, rapid and high throughput
      method for lipase thermo-stability measurement.

PMID- 21847995
TI  - [Repeated batch and fed-batch process for astaxanthin production by Phaffia
      rhodozyma].
AB  - A comparative study of batch and repeated batch process was carried out for
      astaxanthin fermentation of Phaffia rhodozyma to develop a more economical method
      for astaxanthin industrial production. In shaking flask fermentation, the change
      of biomass and astaxanthin production was studied to compare the five-day cycle
      with four-day cycle of repeated batch culture of P. rhodozyma. Astaxanthin
      production increased at first and then decreased subsequently in seven cycles,
      yet the yield of astaxanthin in the next six cycles remains higher than that of
      the first cycle. Comparing the average production of astaxanthin in the seven
      cycles, four-day cycle performed even better than five-day cycle. Subsequently, a
      repeated fed-batch process was used in a 5-1 bioreactor. The experimental data
      showed that biomass and astaxanthin production of the second batch could reach
      the level of the first batch, no matter that the carbon source was glucose or
      hydrolysis sugar of starch. This result showed that this strain had good
      stability, and thus repeated batch and fed-batch process could be applied in
      astaxanthin fermentation for economical purpose.

PMID- 21847996
TI  - [Oxygen evolution characteristics of Spirulina platensis under various light
      conditions].
AB  - The knowledge of oxygen evolution characteristics, which is a symbol of
      photosynthetic activity, under various light conditions is important for
      photobioreactor design and operation. In this study, we constructed a device to
      investigate oxygen evolution characteristics of Spirulina platensis under two
      different light regimes: 1) continuous illumination of various light intensities
      (14-6 500 micromol/(m2 x s)); 2) medium frequency L/D cycles of four different
      light intensities (69, 505, 1 330, 4 265 micromol/(m2s)). Light limited region,
      intermediate region, light saturated region and light inhibited region of light
      intensity were recognized according to their relationship with oxygen evolution
      rate (OER) under continuous illumination. Investigation of S. platensis under L/D
      cycles showed whether photosynthetic efficiency could be increased with
      increasing L/D frequency largely depended on the light intensity applied. The
      higher the light intensity, the larger the photosynthetic enhancement could be
      expected with the increase of L/D frequency. The largest light integration effect
      was found under L/D cycles of high light intensity (4 265 micromol/(m2 x s)) and
      medium light fraction (k = 0.6), while light integration effect was totally
      absent under low light fractions (k < 0.2). We also discussed their implications
      to the practical aspects of microalgae cultivation.

PMID- 21847997
TI  - [Scale-up preparation of phycoerythrin from Porphyra haitanensis].
AB  - We developed large-scale preparation of phycoerythrin from Porphyra haitanensis,
      a main economic red algae in China. Firstly, P. haitanensis thallus was broken by
      using "swelling and smash" method. Then times of grads ammonium sulfate
      precipitation applied to the crude extraction were compared. Desalted solution
      was further purified with one-step chromatography using hydroxyapatite and
      properties on spectrum and molecular weight were identified finally. The results
      indicated that after four times of ammonium sulfate precipitation (15%, 50%, 10%
      and 40%), the absorption spectrum purity of P. haitanensis achieved 0.9
      (A564/A280), and 507.82 mg phycoerythrin (A564/A280 > 3.2) was obtained from 7 kg
      fresh algae after further hydroxyapatite chromatography. This research provides a
      potential way for preparation of phycoerythrin in large sclae.

PMID- 21847998
TI  - [High throughput screening atrazine chlorohydrolase mutants with enhanced
      activity through Haematococcus pluvialis expression system].
AB  - Developing a high-throughput screening method is of great importance for directed
      evolution of atrazine chlorohydrolase. A mutagenesis library of atzA from
      Pseudomonas sp. ADP and Arthrobacter sp. AD1 was constructed using error-prone
      PCR and DNA shuffling. Candidate mutants were screened through Haematococcus
      pluvialis expression system, using atrazine as selection pressure. Sequence
      analysis showed that mutations in the obtained 12 mutants with enhanced activity
      were all point-substitutions and scattered throughout the gene. Enzymatic
      activity analysis showed that the mutants all had higher activities than that of
      the wild type. The activities were 1.8-3.6 fold of the wild-type enzyme when
      cultured in BBM medium with 1 mg/L atrazine, whereas 1.8-2.6 fold with 2 mg/L
      atrazine. These results indicated that Haematococcus pluvialis expression system
      is an ideal high throughput screening system for directed evolution of atrazine
      chlorohydrolase.

PMID- 21847999
TI  - [Performances of anammox-EGSB bioreactors started up with three different seeding
      sludges].
AB  - In order to select better seeding sludge and promote start-up of Anammox
      reactors, we studied the start-up performances of three Anammox-EGSB bioreactors
      inoculated with anaerobic methanogenic sludge (AMS) (R1), Fresh Anammox sludge
      (FAS) (R2) and stored Anammox sludge (SAS) (R3), respectively. Results showed
      that these three seeding sludges could start up Anammox-EGSB bioreactors
      successfully, but the start-up progresses showed different characteristics. The
      start-up course of R1 could be divided into three phases including autolysis
      phase (15 d), lag phase (54 d) and activity elevation phase (40 d). However, the
      start-up courses of R2 and R3 only included lag phase (2 d and 12 d,
      respectively) and activity elevation phase (15 d and 57 d, respectively).
      Besides, the performance of R3 was better than that of R1, but worse than that of
      R2. Furthermore, bathing the Anammox sludge in the effluent of bioreactors was a
      convenient and effective way to keep the activity of the Anammox sludge. The
      ammonia removal efficiency, percentage of denitrification and the stoichiometric
      ratios of NH4(+)-Nr/NO2(-)-Nr and NO3(-)-Np/NH4(+)-Nr could serve as indicators
      to monitor the start-up of Anammox bioreactors.

PMID- 21848000
TI  - [Screening of specific target sequences for the PCR detection of Staphylococcus
      aureus by automatic genomic comparison].
AB  - The aim of this study was to establish a fast and accurate method for developing
      specific DNA sequences and PCR primers for the detection of Staphylococcus
      aureus. An automatic C++ program for genomic comparison was used to identify
      specific DNA sequences from the genome of S. aureus MRSA 252. Four primer pairs
      were obtained from 9 specific target sequences by comparison of 2656 coding
      sequences with our local genome database, and 2 pairs of primers were confirmed
      to be specific to S. aureus by PCR evaluation against 137 bacterial strains,
      including 11 species of Staphylococcus. Furthermore, the DNA detection
      sensitivity of primer SA3 was 13.7 fg/microL and the cell sensitivity for this
      primer was 9.25 x 10(2) CFU/mL. This method has overcome the limitations of
      specific target mining in conventional assays, and it could be easily and widely
      used for other foodborne pathogens.

PMID- 21848001
TI  - [Adherent and single-cell suspension culture of Madin-Darby canine kidney cells
      in serum-free medium].
AB  - In recent years, there are tremendous economic and social losses across the world
      because of virus-related diseases. It is well known that Madin-Darby canine
      kidney (MDCK) cells are easily handled, quickly amplified and efficiently
      infected with influenza virus. Therefore, they are considered as one of the most
      important cell lines for the production of influenza vaccine. In this work, we
      first developed a serum-free adherent culture process for MDCK cells with an in
      house prepared serum-free medium MDCK-SFM. Next, we derived a cell line named ssf
      MDCK, which was amenable for single-cell suspension culture in the serum-free
      medium. We found that during serum-free batch culture of MDCK cells, the peak
      viable cell density and maximum specific growth rate were 3.81 x 10(6) cells/mL
      and 0.056 h(-1), respectively; 3.6- and 1.6-fold increase compared with those in
      serum-containing adherent batch culture. In addition, we compared growth and
      metabolic characteristics of MDCK cells in serum-containing adherent culture,
      serum-free adherent culture and serum-free single-cell suspension culture. We
      found that less metabolic by-products were produced in both serum-free cultures.
      In serum-free single-cell suspension batch culture, the viable cell density was
      highest. These results are critical for establishing large-scale suspension
      culture of MDCK cells as subsequent well as large-scale influenza vaccine
      production.

PMID- 21848002
TI  - [De novo design, non-chromatographic purification and salt-effect of elastin-like
      polypeptides].
AB  - Elastin-like polypeptides (ELPs) are temperature sensitive biopolymers composed
      of a Val-Pro-Gly-Xaa-Gly pentapeptide repeat that derived from a structural motif
      found in mammalian elastin. It was a promising tag for recombinant protein
      purification. Here, we de novo designed a novel ELPs gene and cloned it into the
      modified expression vector pET-22b(+). Then, we transformed the recombinant
      expression vector pET-22b-ELPs into Escherichia coli BL21(DE3). Upon induction by
      Isopropyl beta-D-Thiogalactoside (IPTG), ELPs was expressed and purified by a non
      chromatographic purification method named inverse temperature cycling. The
      influences of salts types and concentrations on ELPs were also determined. The
      results showed that the transition temperature of the [KV8F-20] decreased to 19
      degrees C by 0.4 mmol/L Na2CO3. Due to its small molecular weight and sensitivity
      to salt, the ELPs might be a useful purification tag, which can provide a
      reliable and simple non-chromatographic method for purification of the
      recombinant protein by inverse transition cycling.

PMID- 21848003
TI  - [Expression of human aspartyl beta-hydroxylase and preparation of its monoclonal
      antibody].
AB  - We investigated the mechanism of human aspartyl beta-hydroxylase (HAAH) in early
      diagnosis of tumors. The encoding gene of HAAH was cloned from the hepatic
      carcinoma by RT-PCR and expressed as a fused protein in the prokaryotic vector
      pBV-IL1. The expressed HAAH was purified by Ni(2+)-NTA purification column and
      the purified protein was then used to immunize Balb/c mice. Three hybridoma cell
      lines (respectively designated H3/E10, E4/F12 and G4/D8) stably expressing the
      monoclonal antibody specific to HAAH fusion protein were obtained. The
      specificity and sensitivity of the monoclonal antibody were assessed by indirect
      enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Finally, the
      monoclonal antibody expressed by H3/E10 cell line was used to detect the
      expression of HAAH in several tumor cell lines by indirect immuno-fluorescence,
      and the specific fluorescence was observed. In conclusion, this study
      successfully constructed the recombinant prokaryotic vector pBV-IL1-HAAH and
      prepared HAAH-specific monoclonal antibody for further study of the structure and
      function of the protein. The result may also lay solid foundation for the
      research of the molecular mechanism of HAAH in early diagnosis of tumors.

PMID- 21848004
TI  - New phenotype with generalized platyspondyly, large mandible, hypoplastic teeth,
      strabismus, hyperopia and low cholesterol levels.
AB  - A sporadic, adult male patient with generalized platyspondyly, large mandible,
      hypoplastic teeth, strabismus, and low serum cholesterol levels is presented.
      Some of the patient's features resemble brachyolmia, Spondylo-epiphyseal
      dysplasia tarda, Kenny-Caffey and Stickler syndromes. Based on literature review,
      possible diagnoses are discussed. In conclusion, this patient can have a variant
      of brachyolmia or Spondylo-epiphyseal dysplasia tarda. However, we cannot exclude
      that this constellation of clinical features may represent a new syndrome.

PMID- 21848005
TI  - The role of genomics in prevention or reducing the impact of congenital
      malformations.
AB  - Congenital malformations (CMs) are permanent changes produced by abnormality of
      development in a body structure during prenatal life. Population based studies
      place the incidence of major malformations at about 2-3% of all live births. The
      etiology is mostly due multifactorial inheritance or unknown (50-80%). The
      continuum and gradual shift from genetics to genomics will offer new
      possibilities for diagnosis, treatment, prediction and prevention of congenital
      malformations. Genomics has many tools including pathogenomics, pharmacogenomics,
      nutrigenomics and bioinformatics. Pathogenomics will help to discover new genes
      or susceptibility genes and genetic variants with a role in the pathogenesis of
      CMs. Pharmacogenomics will identify genetic variants affecting the response to
      drugs and it should be applied to study drug induced birth defects. Nutrigenomics
      will determine the impact of diet on genome stability and how genotype determines
      nutritional requirements. Bioinformatics then will collect, store obtained data,
      which will facilitate analysis of systems biology questions involving
      relationships between genes, their variants and biological functions. This
      knowledge should be translated into more sensitive and specific genetic tests.

PMID- 21848006
TI  - Linkage analysis and a novel COL4A5 mutation in a large Turkish family with
      Alport syndrome.
AB  - BACKGROUND: Alport syndrome (AS) is a renal disease that is characterized by
      proteinuria and progressive renal failure, and often accompanied by sensorineural
      hearing loss and ocular changes. Mutations in the genes encoding for three
      members of the type IV collagen protein family have been found to be the cause of
      the disease. We describe a large Turkish family with X-linked AS. We performed
      linkage analysis in this family and sequencing to identify the mutation in the
      proband whose disease was confirmed by renal biopsy. METHODS: After genomic DNAs
      extracted, linkage to the COL4A5 locus was examined using the 2B6 and 2B20,
      DXS1106, DXS1105 and COL4A5 markers. In addition, COL4A5 gene sequence analysis
      was performed in the proband. RESULTS: Genetic linkage analysis demonstrated co
      segregation of the disease. Haplotype analysis showed that the same haplotype was
      carried by all affected males and obligatory carrier females. Mutation analysis
      of the proband has revealed a novel nonsense mutation (c.1135C>T; Gln379X) in
      exon 19 of the COL4A5 gene which may lead to a more severe phenotype in affected
      family members carrying this mutation. According to GenBank data base, this
      mutation has not been reported previously. CONCLUSION: Genetic testing identified
      a previously undescribed COL4A5 mutation as the cause of the disease.

PMID- 21848007
TI  - Aniridia phenotype and myopia in a turkish boy with a PAX6 gene mutation.
AB  - A boy with bilateral aniridia, iris coloboma, glaucoma, myopia and slight
      developmental delay was found to have a frame shift mutation in the PAX6 gene.
      The c.474delC mutation was de novo and both parents had a normal eye phenotype.

PMID- 21848008
TI  - A neonatal case of left ventricular noncompaction associated with trisomy 18.
AB  - A neonatal case of left ventricular non-compaction associated with trisomy 18:
      Left ventricular noncompaction (LVNC) is a rare congenital cardiomyopathy and
      exact etiology is still unknown. Trisomy 18 is the second most common autosomal
      trisomy in live-born infants. LVNC has been described in association with other
      dysmorphic features, association with trisomy 18 has not been reported previously
      in a neonate. LVNC broadens the cardiac anomalies associated with trisomy 18.

PMID- 21848009
TI  - Ring chromosome 18 in a child with febrile seizures.
AB  - Ring chromosomes are uncommon cytogenetic findings but have meanwhile been
      reported for nearly all human chromosomes. Among the rare observations of ring
      chromosomes in man, the diagnosis of ring chromosome 18 represents a prominent
      group. We here describe on the cytogenetic analysis results obtained for a 9
      years old male patient of non-consanguineous parents. He had growth and
      developmental delay, mental and motor retardation, microcephaly, microphtalmia,
      triangle face, small dysplastic ears, strabismus, epicanthal folds on the left,
      short stature, cryptorchidism, spasticity, pes equinovarus, pes planus,
      hypothroidism, stereotypic movements and febrile seizures. Also he had
      hypomyelinization and multiple hyperintense focuses within the white matter on
      the MRI. The generalized epileptiform abnormality originated from bilateral
      Centroparietal region. The metabolic investigations including blood and urine
      amino acids and lysosomal screening tests were normal. The chromosome analysis
      identified [46,XY,r(18)/46,XY] in 35% of cells a ring 18 and in 65% of cells
      normal karyotype in peripheral blood cells examined by standard G-bands by
      Trypsin using Giemsa (GTG) analysis. The dysmorphic features of the presented
      patient are discussed to the identification of the genotype-phenotype correlation
      related to his karyotype.

PMID- 21848010
TI  - Dysmorphological and pharmacological studies in 4q- syndrome.
AB  - The 4q- syndrome includes interstitial and terminal deletions of the long arm of
      chromosome 4. In this study 22 children with 4q- were evaluated through face-to
      face assessments and/or two-dimensional digital photographs. In addition, 15
      parents participated in a questionnaire survey regarding pharmacological and
      other treatments which their affected child received. A high forehead was seen in
      73% of index cases and was the only facial feature consistently present in this
      group. There may be a link between this phenotypic characteristic and the
      increased incidence of autistic spectrum disorder in 4q deletion syndrome (33%).
      Two thirds of the subjects were taking long term prescription drugs and/or food
      supplements. Commonly used nutritional supplements were multivitamins, carnitine,
      coenzyme Q10 and omega-3 fatty acids. They were well tolerated by the probands
      but the literature evidence for their specific effectiveness was weak. Twelve out
      of 15 children had speech and language therapy, occupational therapy or
      physiotherapy, and 6/15 regularly saw a psychologist. Future 4q- research should
      focus on gene-phenotype correlations, 3D face analysis and drug treatment to
      improve global and medical functioning.

PMID- 21848011
TI  - A novel mutation of the claudin 16 gene in familial hypomagnesemia with
      hypercalciuria and nephrocalcinosis mimicking rickets.
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is
      caused by a mutation in the gene CLDN16, which encodes paracellin 1 (claudin-16),
      atight junction protein mediating paracellular transport which is expressed in
      the thick ascending loop of Henle and in the distal convoluted tubule, where
      reabsorption of magnesium occurs. We present a 4 years old Turkish female child
      with a chief complaint of hypocalcemic tetany. A diagnosis of FHHNC was confirmed
      by genetic testing for a mutation in claudin 16 gene. Claudin 16 gene revealed
      homozygosity for the p.K183E(AAA>GAA) C. 547A>G indicating the diagnosis of
      hypomagnesemia with hypercalciuria and nephrocalcinosis. To our knowledge, this
      is the first case of FHHNC reported in Turkish population diagnosed at molecular
      level.

PMID- 21848012
TI  - Ovulation induction with gonadotropins causes increased sister chromatid
      exchanges.
AB  - Gonadotropins are widely accepted agents for ovulation induction in infertile
      women. On the other hand, several authors discuss the possible effect of
      gonadotropins on the developmental mechanism of ovarian cancer. SCE is a method
      of genotoxicity investigation and it is an excellent parameter to monitor the DNA
      damage and repair. There are numbers of studies showing the relationship between
      endogenous or exogenous hormones and SCEs. The aim of this study was to
      investigate with SCE techniques the effects of long-term (6 months) use of
      gonadotropins on DNA as we couldn't find any other study on the effect of long
      term use. We found increased sister chromatid exchange rates in a study group as
      compared to a control group. This may be one of the causes of increased ovarian
      cancer risk in infertile population.

PMID- 21848013
TI  - Partial trisomy 3q in a child with sacrococcygeal teratoma and Cornelia de Lange
      syndrome phenotype.
AB  - Partial duplication of 3q is a rare chromosomal disorder that leads to multiple
      congenital abnormalities such as growth retardation, microcephaly and
      characteristic facial features. Although the phenotype of the patient has
      similarities with Cornelia de Lange Syndrome they are etiologically different. We
      report here a 9 months old baby boy with partial duplication of 3q and features
      similar with Cornelia De Lange syndrome. Conventional cytogenetic analysis
      revealed a derivative chromosome 21. In order to determine the origin of this
      chromosome region we used subtelomeric FISH technique. Based on the results of
      all these cytogenetic studies and the physical examinations, the diagnosis is
      partial 3q duplication.

PMID- 21848014
TI  - Can fetal ultrasound result in prenatal diagnosis of Prader-Willi syndrome?
AB  - OBJECTIVE: To define fetal ultrasound characteristics triggering an antenatal
      diagnosis of Prader Willi syndrome (PWS). METHODS: Retrospective analysis of
      sonographic characteristics retrieved from obstetric ultrasound records. All
      children (n=11) had a postnatal genetically confirmed diagnosis of PWS. RESULTS:
      All patients (n=11) showed at least one aspecific abnormality on prenatal
      ultrasound. Ten out of eleven (90.9 %) had decreased fetal movements, 7 (63.6%)
      presented in breech position, 7 (63.6%) had severe intra-uterine growth
      restriction (<5th centile) and 4 (36.4%) showed a polyhydramnios. Immobile flexed
      limbs and clenched hands were seen in one patient (9.1%). Severe growth
      restriction combined with polyhydramnios favors the diagnosis in 3/11 cases.
      CONCLUSION: Prenatal sonographic phenotype of PWS includes decreased fetal
      movements, fetal malpresentation, severe intra-uterine growth restriction and
      polyhydramnios. These findings are not specific to PWS, but the combination of
      some of them (especially severe intra-uterine growth restriction and
      polyhydramnios) can prompt clinicians to perform invasive testing leading to a
      molecular cytogenomic diagnosis prenatally.

PMID- 21848015
TI  - An infantile case of Zellweger syndrome presented with Kabuki-like phenotype.
AB  - Zellweger syndrome is a peroxisomal disorder resulting from the mutations in PEX
      genes generally presenting in the neonatal period with profound hypotonia
      seizures, inability to feed, liver cysts with hepatic dysfunction,
      chondrodysplasia punctata. Kabuki make-up syndrome is a multiple congenital
      anomalies and mental retardation syndrome with characteristic facial appearance,
      skeletal abnormalities, dermatoglyphic abnormalities, mental retardation and
      short stature. Abnormal liver functions and some atypical findings were also
      reported in some patients with Kabuki syndrome. In this report a case with late
      onset Zellweger syndrome who had some phenotypical findings which are also seen
      in Kabuki Syndrome will be presented. The inclusion of Zellweger syndrome into
      the differential diagnosis of the patients with Kabuki-like phenotype in addition
      to abnormal liver functions is emphasized.

PMID- 21848016
TI  - A case of congenital warfarin syndrome due to maternal drug administration during
      the pregnancy.
AB  - Warfarin, which is used for anticoagulant therapy, rarely produces congenital
      warfarin syndrome characterized with hypoplastic nose, stippled epiphyses, and
      skeletal abnormalities when ingested during pregnancy. Here, we present a male
      infant, whose mother was treated with warfarin because of a prosthetic heart
      valve replacement after rheumatic heart disease, with signs of warfarin
      embryopathy. The mother's first pregnancy at 12 weeks gestation resulted in
      abortus due to warfarin toxicity. Subsequently, she delivered two healthy girls
      after her treatment had changed to low molecular heparin during pregnancy
      periods. We want to emphasize that risk-benefit ratio should be well weighed by
      both obstetricians and cardiologists when considering warfarin therapy for a
      woman at childbearing age.

PMID- 21848017
TI  - A rare case of monosomy 18p: translocation between chromosomes 18 and 21.
AB  - A rare case of monosomy 18p with molecular cytogenetic characterization of 18;21
      whole arm translocation is presented. An 8-year-old gril with mental deficiency
      and growth deficiency was the child of a 45-year-old healthy mother and 50-year
      old nonconsanguineous father with unremarkable prenatal history. She had a round
      face, flat nasal bridge, micrognathia and hypotonia. Cytogenetic studies revealed
      de novo 45,XX,del(18)t(18;21) karyotype, which was confirmed by fluorescence in
      situ hybridization (FISH).

PMID- 21848018
TI  - Group leadership during the change process.

PMID- 21848019
TI  - Data bits. Discharge education to prevent readmissions in older patients.

PMID- 21848020
TI  - Cultural humility in the practice of medicine.

PMID- 21848021
TI  - Obesity and dyslipidemia.
AB  - Dyslipidemia is frequently found in association with obesity. Obesity-related
      dyslipidemia is characterized by elevated triglycerides, elevated VLDL, increased
      apo-B, decreased HDL cholesterol and increased small dense LDL particles. This
      combination of lipid abnormalities is particularly atherogenic and, along with
      related comorbidities, explains the increased cardiovascular risk seen in
      obesity. Weight loss, through diet, medication and/or surgery all result in
      beneficial effects upon serum lipids. Dietary modification and lifestyle change
      are essential components in the management of obesity-related dyslipidemia. Many
      patients, however, require pharmacotherapy to achieve lipid goals.

PMID- 21848022
TI  - Obesity and fertility.
AB  - Obesity has an overall negative impact on fertility, affecting both women and
      men. Not only are obese individuals more likely to experience infertility, they
      are less likely to benefit from fertility treatment. Moreover, achieving
      pregnancy may place obese women at high risk for serious complications. It is
      important that obese individuals understand the effects that their obesity can
      have on reproductive function.

PMID- 21848023
TI  - Atrial fibrillation treatment update.

PMID- 21848024
TI  - Feds implement priorities of National Quality Strategy.

PMID- 21848025
TI  - New technology assessment: riding the bullet train.

PMID- 21848026
TI  - How to read a dental research paper.

PMID- 21848027
TI  - Preventive and interceptive orthodontics for the 5 to 12 year-old. Functional
      appliances: the Nite-Guide and Occlus-o-Guide techniques.
AB  - hree orthodontic procedures are described that are used to prevent, intercept,
      and correct malocclusions at three distinct stages of dental development. Each
      stage of development (5 to 7 years, 8 to 12 years, and 12 years through
      adulthood) uses an appliance selected from a series of several preformed sizes.
      All have predicted socket dimensions to receive unerupted, erupting or fully
      erupted teeth. These sockets are prearranged in a perfect Class I occlusion. In
      the first group of appliances, specifically designed for the 5 to 7 year-old
      (called Nite-Guide), one selects a single size that is large enough to
      accommodate the teeth after they become straight. This appliance is worn
      passively while sleeping and simply guides the incoming incisors to straighten
      themselves using only their own force of eruption. Once straight, the adult
      collagenous fibers form and thereby prevent most future relapse from occurring.
      At the same time, the incoming incisors are prevented from over-erupting into a
      deep overbite and the mandible is advanced to correct any excess overjet.
      Similarly-designed appliances are also used to correct malocclusions in the mixed
      and adult dentitions. To obtain optimum results at these ages, active wear of
      about two hours per day is required. The treatment time is very fast (1 to 12
      months in most cases) and the same appliance is also used as the retainer of
      choice. Most malocclusion problems such as crowding, rotations, overbite, overjet
      and TMD are 80 to 95% corrected in those wearing the appliance as directed.

PMID- 21848028
TI  - Vascular mechanism of spongious dental anesthesia.
AB  - By their mechanism of action local anesthesia methods are divided into diffuse
      and vascular. Anesthesias are vascular at arteriolo-capillary-venous system
      level. Besides more than 2-fold efficacy increase, circulatory mechanism also
      contributes to enhancement of cardiovascular system reactions.

PMID- 21848029
TI  - [Apical root end resection (Apicoectomy) as treatment option in cases of dental
      trauma in young patient].
AB  - Apical root end resection is becoming popular procedure as a treatment option in
      cases of ortho-grade endodontic failure. In this case report it has been shown
      that root end resection (Apicoectomy) had succeed to preserve a tooth after
      dental trauma with root fractured in the apical third. Any other conservative
      endodontic treatment failed. One-year follow-up revealed complete healing of the
      area. Apical root end resection might serve as a viable treatment option in cases
      of dental trauma in young patient in carefully selected patients.

PMID- 21848030
TI  - [The use of antibiotic prophylaxis prior to dental procedures for the prevention
      of prosthetic joint infection].
AB  - Prosthetic joint infection (PJI) is a severe illness which may cause pain and
      discomfort, may damage the quality of life and may even be life-threatening. A
      variety of studies have demonstrated the presence of bacteria in a small but
      potentially dangerous number of prosthetic joint infections that may have
      originated in the oral cavity. Some dental treatments such as calculus removal,
      extractions, dental implants placements etc. and daily oral hygiene routines such
      as tooth brushing may cause bacteremia. Recently the American Academy of
      Orthopaedic Surgeons (AAOS) published updated guidelines for antibiotic
      prophylaxis to prevent prosthetic joint infections. These guidelines suggest a
      direct and established connection between dental treatments and prosthetic joint
      infections, and expand the criteria to prescribe antibiotic prophylaxis prior to
      dental procedures associated with bacteremia. The purpose of this review is to
      introduce these new guidelines, and to review the literature regarding the
      relationship between dental care and prosthetic joint infections.

PMID- 21848031
TI  - [Elastomeric impression materials].
AB  - Elastomeric impression materials are in common use. The impression taken should
      be highly precise, thus, requiring specific care when manipulatingthese
      materials. There are 4 groups of elastomers; polysulfide, condensation silicone,
      addition silicone and polyether; each differ in their setting mechanism and their
      physical and chemical properties. This review elaborates the major properties of
      elastomers and its implications on their use. The impression material is inserted
      into the patient's mouth in a viscous state and transforms into viscoelastic
      state, upon withdrawal, influencing the residual deformation. The requirements
      are minimal residual deformation or maximal elastic recovery. As the mouth is a
      wet environment a major consideration is hydrophilicity. The wettability which is
      estimated by measuring either the contact angle of a droplet of water and the
      substrate post setting or the contact angle of a droplet of impression material
      and the wet tooth pre setting, determines the interaction of the material with
      both mouth fluids and gypsum. As the primary end target is to obtain a model
      depicting accurately the oral details, an attention to the impressions'
      compatibility with gypsum should also be given. Many studies were conducted to
      get a thorough understanding of the hydrophilic properties of each material, and
      the mechanism utilized, such as surfactants in hydrophilic PVS. Polyether is the
      only material that is truly hydrophilic; it exhibits the lowest contact angle,
      during and after setting. Recent studies show that during setting the Polyether
      hydrophilicity is increased compared to the condition after setting. Dimensional
      stability, a crucial property of the impression, is affected by the physical and
      chemical attributes of the material, such as its tear strength. Polysulfide has
      the highest tear strength. Tear Strength is affected by two major parameters,
      viscosity, a built-in property, and how fast the impression is pulled out of the
      mouth, the faster the impression is loaded and pulled out, the higher the tear
      strength is. The clinical use is dictated from the properties of each impression
      material, and the understanding of those enables the practitioner to minimize
      failures.

PMID- 21848032
TI  - [Online conferences].

PMID- 21848033
TI  - Comparing validation of four ELISA-systems for detection of Salmonella derby- and
      Salmonella infantis-infected pigs.
AB  - The objective of this study was the comparative evaluation of four indirect
      Salmonella ELISA tests at study time approved in Germany to detect Salmonella
      infection in pigs.Three tests are based on a LPS-antigen mix and directed against
      specific IgG antibodies. The fourth test is based on a purified S. Typhimurium
      whole-cell lysate antigen and discriminates between Salmonella-specific IgM-, IgA
      , and IgG- antibodies. In a longitudinal study, two groups of six weeks old
      hybrid piglets were orally infected with a porcine S. Infantis or S. Derby
      strain. Clinical and bacteriological parameters were monitored weekly during an
      observation period of 130 days after infection and serum samples were
      investigated in parallel with the respective ELISAs. Apparently, the LPS-based
      ELISA systems used in this study failed to recognize S. Infantis-infected pigs
      although those animals shed the pathogen in high amounts throughout the study
      until day 81 post infection (p. i.). In contrast, the isotype-specific Salmonella
      Typhimurium whole-cell-lysate based ELISA was capable of detecting Salmonella
      infected pigs from day ten p. i. at all tested serotypes and revealed the highest
      sensitivity in detection of S. Infantis-infected pigs. Furthermore, it became
      apparent that the often used surveillance cut-off value of 40 OD% is not
      appropriate for intra-vitam detection of S. Infantis- and S. Derby-infected pigs.
      In contrast, the cut-off values of the ELISAs given by the suppliers result in
      considerable higher detection rates.

PMID- 21848034
TI  - Evaluation of claw health in heifers in seven dairy farms using a digital claw
      trimming protocol and claw data analysis system.
AB  - The claw health of 139 heifers with a mean age of 22.1 months (SD: 2.6) in seven
      free stall dairy farms in Lower Austria was evaluated. Claw lesions were assessed
      during functional claw trimming and documented and analysed using the digital
      program Claw Manager. For documentation of lesions, each claw was divided into
      ten zones. The prevalence of lameness, claw lesions and their severity were
      determined, furthermore the Cow-Claw-Scores (CCS), Farm-Claw-Scores (FCS) and
      Farm-Zone-Scores (FZS) were calculated.The FCS between farms was tested for
      significant differences. A lameness prevalence of 9.4% and an overall prevalence
      of claw lesions of 98.5% were recorded in these 139 heifers.The most commonly
      diagnosed disorders were white line lesions (WLL) with a prevalence of 87.1%,
      heel horn erosion (84.9%), double soles (DS; 47.5%), sole haemorrhages (SH;
      33.1%) and a concave dorsal wall contour in 15.1% of the heifers. High
      correlation coefficients (r > or = 0.93) were found between SH and DS, WLL and
      DS. 86.5% of all diagnosed claw lesions were score 1 (mild), 11.1% score 2
      (moderate) and 2.4% score 3 (severe) lesions. The CCS in all heifers ranged
      between 0 and 267, and the FCS in the seven herds was between eleven and 55. Claw
      zone 3 was affected most frequently and severely. Following the results of this
      study, systematic functional claw trimming and consequent documentation of
      detected claw lesions is highly recommended for heifers at the time of their
      first insemination to prevent claw disorders in lactating cows and to improve
      their well-being.

PMID- 21848035
TI  - Lack of evidence for claims of farmers in south-eastern Germany regarding adverse
      reactions ascribed to BTV-8 vaccines.
AB  - Farmers in south-eastern Germany who claimed adverse reactions due to the
      application of BTV-8 vaccines during the compulsory vaccination programme in
      2008/2009 were invited to participate in an epidemiological study to prove
      whether there was evidence for a plausible relationship between the immunizations
      and the reported symptoms. Ten farms were available for on-site visits; all other
      farmers (N = 120) who had registered to participate in the study were asked to
      complete a questionnaire and to provide evidence for the claimed adverse
      reactions. 25 questionnaires were returned. Although a wide range of symptoms
      were reported, in most cases the documentation of clinical signs, pathological
      alterations and fatalities was not sufficient to conclude on a causal
      relationship. Similarly, most of the suspected adverse events evaluated as
      pharmacovigilance reports had to be categorized as "unclassified due to
      insufficient information".

PMID- 21848036
TI  - [Evaluation of four commercial RT-qPCR test kits for detection of Bluetongue
      virus RNA].
AB  - Since 2006, the occurrence of bluetongue in Northwest- and Central Europe has
      lead to extensive financial losses. For first-line laboratory diagnosis, reverse
      transcription real-time PCR (RT-qPCR) has been used increasingly, necessitating
      careful evaluation of all applied methods by the performing laboratory. In the
      course of an internal validation, four commercially available BTV RT-qPCR kits
      and two published reference methods were compared. Clear differences regarding
      reaction kinetics, analytical as well as diagnostic sensitivity and specificity
      were observed. Furthermore, test kits were not equally suitable for testing
      samples from a selection of BTV-susceptible host species. Only two commercial
      kits were in all examined parameters equal to, or superior than, the more
      demanding reference methods and thus represent a possible alternative to using
      published methods for BTV RT-qPCR screening.

PMID- 21848037
TI  - [Epidemiological enquiries in two Q fever outbreaks in a community of Baden
      Wurttemberg during 2008 and 2009].
AB  - In 2008 and 2009, two consecutive outbreaks of Q fever in humans were recorded in
      the district of Freudenstadt, northern Black Forrest, Baden-Wurttemberg, Germany.
      In 2008, a total of 41 persons from a single local community fell ill and were
      found infected with Coxiella burnetii. Although comprehensive diagnostic and
      epidemiological outbreak investigations were conducted and control measures taken
      which included vaccination of ruminants at risk in three parts of the affected
      community, re-occurrence of the disease in 2009 with further 29 confirmed human Q
      fever cases could not be prevented. While the origin of infection of the first
      outbreak was probably a flock of 550 sheep moved in the surrounding of the
      affected villages, the source of infection for the consecutive outbreak in 2009
      could not be identified. It seems possible that meadows contaminated with
      infectious placenta or birth fluids represented the sources of infection.

PMID- 21848038
TI  - [Phage therapy in the fields of veterinary medicine: an overview].
AB  - During the last years, bacteriophages have been used as valuable tool in
      microbiological diagnostics and basic research. Even though the potential of
      bacteriophages for fighting bacterial pathogens is known for a long time, the
      phage therapy is not used in daily routine worldwide. Due to the continuing
      spread of bacterial resistance to antimicrobials and an increasing awareness of
      the necessity to protect consumers' health, the phage therapy meanwhile has
      become a subject of major interest in veterinary medicine, too.This article is
      meant to present fields of application for phage therapy as well as current
      trends of development in the field of livestock animals.

PMID- 21848039
TI  - [Comparing the results of the serological detection of Salmonella antibodies in
      blood serum and meat juice from different muscles from slaughter pigs].
AB  - The German Salmonella Monitoring Programme started by the QS-System in 2002
      (Blaha, 2004) is mandatory due to the so-called "Salmonella Regulation for Pigs"
      since 2007 (Anonym, 2007). The Regulation does not clearly prescribe the specific
      muscle which is to be taken as source of the meat juice. Thus, at different
      slaughter plants meat samples are also taken from different muscles and several
      scientific papers describe various muscles as source of the meat juice, too. The
      objective of this study was to compare the serological results of meat juices
      from three different locations (diaphragm pillar, neck, belly muscle) to each
      other and to those of the blood serum from exactly the same animals. All samples
      were simultaneously tested for Salmonella antibodies by two serological tests
      (Salmo-type Pig Screen, LDL, Germany; HerdChek Swine Salmonella, IDEXX, Germany).
      Comparisons were carried out between the various sample kinds per animal and
      between the two test systems. The analysis of all results of the meat juices
      revealed in both test systems a clear decline of the OD% values from the
      diaphragm pillar to the neck to the belly muscle. The average OD% values of all
      samples were higher when measured by the HerdChek ELISA (IDEXX, Germany) than by
      the Salmotype ELISA (LDL, Germany), especially in blood serum. Since the results
      of the meat juice samples gained from the diaphragm pillar were in both test
      systems by far the closest to the results of the corresponding serum blood
      samples, it is recommended to amend the "Salmonella Regulation for Pigs" by
      prescribing meat from the diaphragm pillar as the only muscle for gaining meat
      juice.

PMID- 21848040
TI  - Phenotypic and molecular characterization of Yersinia ruckeri isolates from
      rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) in Turkey.
AB  - The aim of the study was the phenotypic and molecular characterization of
      Yersinia (Y) ruckeri strains, the causative agent of Enteric Redmouth Disease
      (ERM), by antibiotyping, random amplified polymorphic DNA-polymerase chain
      reaction (RAPD-PCR) and sodium dodecylsulphate-polyacrylamide gel electrophoresis
      (SDS-PAGE) patterns of whole cell proteins. For this aim, a total of 97 Y ruckeri
      isolates were analyzed. The isolates were distinguished into ten antibiotypes and
      six phenotypes according to their resistance properties and whole cell protein
      profiles, respectively. Also, a glycoprotein band of approximately 25.5 kDa was
      observed in all Y ruckeri strains tested. In all strains, six different RAPD
      types were observed. In conclusion, Y ruckeri strains isolated from rainbow trout
      of fish farms in Turkey showed variation according to their phenotypic and
      genotypic characteristics, and the use of these three typing techniques in double
      and triple combinations could be more useful for discriminating the strains.

PMID- 21848042
TI  - A follow up study on antibodies against Lawsonia intracellularis in mares and
      foals from two breeding farms in Germany.
AB  - Equine proliferative enteropathy (EPE) caused by Lawsonia (L.) intracellularis is
      an emerging disease in foals, particularly in North America. Since a case report
      in Germany exists, the objective of this study was to examine the incidence of L.
      intracellularis-antibodies in healthy horses from two German breeding farms. In
      group 1, serum samples from 24 (year 1) and 16 (year 2) Haflinger mares and their
      foals were taken. In group 2, over a period of five months, serum samples of six
      warmblood mares and foals were collected monthly from birth until the foals
      became seronegative. Serum samples were tested using an ELISA system. Results are
      expressed as Percentage of Inhibiton (PI). All adult mares (100%) of both groups
      were seropositive at each point in time (PI-value > 30). In group 1,7/24 foals
      (29.2%) in year 1 and 4/16 foals (25%) in year 2 had antibodies.The seropositive
      foals from year 2 had the same dams as the seropositive foals from year 1. In
      group 2 five of six foals were seropositive after birth. Antibodies decreased
      from March to July in mares and foals. In July, all five foals tested negative
      for the first time between the ages of 82 and 141 days (median 115 days). PI
      values of mares were significantly correlated with PI-values of their foals.
      Higher PI-values were seen in younger foals and early in spring. Loss of
      antibodies in foals at the age of three to five months could be a risk factor for
      infection and appearance of EPE.

PMID- 21848041
TI  - [Bovine neonatal pancytopenia in German Holstein calves].
AB  - Profiles of blood cell counts were evaluated for 15 calves from three different
      farms. These calves showed petechia in the mucous membranes and in the skin and
      prolonged secondary bleeding after puncture. The clinical course of the disease
      could be observed in eleven calves. With exception of one case, the blood cell
      counts indicated a severe anaemia, leukocytopenia and thrombocytopenia. Out of
      these 15 calves, six calves survived and the other nine calves died or had to be
      euthanized due to the severity of the disease. Necropsy of these nine calves
      revealed petechia in the skin, subcutis, muscles, in inner organs and all serous
      membranes. Pathohistological examination showed a depletion of the bone marrow
      and lymphatic tissue in eight calves. These findings confirmed the diagnosis of
      bovine neonatal pancytopenia (BNP) for eight of these nine calves. Bluetongue
      virus serotype 8 was tested negatively using PCR. Bovine virus diarrhoea virus
      (BVDV) was negatively tested using immunofluorescence and cell culture and
      salmonella species were negatively tested in seven dissected calves. A cluster of
      toxins was negatively tested in one of the dissected calves. All 15 calves had
      high antibody titres for BVDV. The BVDV-antibody titres from twelve dams with
      affected calves were positive in six cases and not detectable in the other six
      cases. In three of the six dams with not detectable BVDV-antibody titres, calves
      were fed with colostrum of a further dam with high BVDV-antibody titres. In the
      further three dams without detectable BVDV-antibody titres, we could not
      ascertain which colostrum has been fed to the calves. BVDV-specific antigen could
      not be detected in any of the samples from the calves and dams tested. Using the
      activity of the gamma-glutamyl-transferase, we assumed a sufficient supply with
      colostrum for the examined calves.The cause for the occurrence of these BNP cases
      was due to bone marrow depletion.The reason for the bone marrow depletion
      remained unclear. However, it was obvious that the BNP described here is highly
      likely caused by colostrum from cows with positive BVDV-antibody titres.

PMID- 21848043
TI  - Expanded data from the new birth certificate, 2008.
AB  - OBJECTIVES: This report presents data for selected items exclusive to the 2003
      U.S. Standard Certificate of Live Birth as well as key items considered not
      comparable between the 1989 (unrevised) and 2003 (revised) versions for states
      and territories that implemented the 2003 revision as of January 1, 2008.
      Information is shown for educational attainment, tobacco use during pregnancy,
      month prenatal care began, and checkboxes in the following categories: "risk
      factors in this pregnancy," "obstetric procedures," "characteristics of labor and
      delivery," "method of delivery," "abnormal conditions of the newborn," and
      "congenital anomalies of the newborn." METHODS: Descriptive statistics are
      presented on births occurring in 2008 to residents of the 27 states that
      implemented the revised birth certificate. RESULTS: There were 2,748,302 births
      to residents of the 27-state reporting area, representing 65 percent of 2008 U.S.
      births. About 78 percent of women had at least a high school diploma; 24.5
      percent had an advanced education. One out of 10 women smoked during pregnancy
      (24-state reporting area) and one out of five smokers quit while pregnant. Almost
      three-quarters of women began prenatal care in the first trimester of pregnancy.
      The rate of prepregnancy diabetes was 6.5 per 1,000 and gestational diabetes was
      40.6; risk of both types rose with maternal age. Nearly one out of four women had
      a primary cesarean delivery; less than 1 out of 10 women had a vaginal birth
      after cesarean delivery. About 27 percent of women attempted a trial of labor
      before a cesarean delivery. Seven percent of all infants were admitted to a
      neonatal intensive care unit.

PMID- 21848044
TI  - 2010 BLS and ACLS guideline changes: post-cardiac arrest syndrome and therapeutic
      hypothermia.

PMID- 21848045
TI  - Predictors of cardiac symptom attribution among AMI patients.
AB  - BACKGROUND: Care-seeking delay represents a major cause of death and disability
      for cardiac patients. With more than 70,000 new and recurrent acute myocardial
      infarctions (AMI) in Canada each year, recognizing symptoms as heart-related and
      seeking prompt medical care is essential for increasing the likelihood of
      successful treatment and survival. However, little is known about the factors
      associated with whether or not individuals attribute their symptoms to the heart
      (i.e., adopt a cardiac symptom attribution). PURPOSE AND DESIGN: Secondary
      analyses were conducted on data from a sample of 135 patients from four North
      American hospitals to identify the predictors of correct symptom attribution
      (CSA) during AMI. RESULTS AND CONCLUSIONS: Logistic regression investigations
      revealed that patients with a prior diagnosis of coronary heart disease and
      patients whose AMI experience paralleled their pre-existing symptom expectations
      were associated with greater odds of adopting a CSA. Results suggest that patient
      education and a clearer understanding of patients' beliefs about AMI can help
      nurses in acute care and community settings identify and manage misconceptions
      that may interfere with correctly attributing symptoms to a cardiac cause.

PMID- 21848046
TI  - Family presence during cardiopulmonary resuscitation: cardiac health care
      professionals' perspectives.
AB  - BACKGROUND: Family presence (FP) during cardiopulmonary resuscitation (CPR) is
      becoming an increasing practice. Within current literature, the attitudes and
      beliefs towards FP of cardiac health care professionals in Canada are limited.
      PURPOSE: The purpose of this project was to examine the perceptions of cardiac
      health care professionals (n=368) concerning FP during CPR. METHOD: A survey was
      conducted to explore the attitudes and beliefs of cardiac health care
      professionals towards family presence during CPR within five Edmonton and
      surrounding area hospitals. RESULTS: The response rate was 46%, with the greatest
      response from nurses and physicians. Of the respondents, 44.3% believed that
      family should have the option to be present, and 40.9% believed that family
      should be allowed at the bedside during CPR. Less than half of the respondents
      had experience with FP during CPR. The barriers identified towards FP were lack
      of support for families, the experience would be too traumatic for families,
      families would not understand the procedures, fear of families physically
      interfering with procedures, FP would increase stress levels among staff, and
      tradition and politics excludes FP. CONCLUSION: Despite less than half the
      respondents supporting FP the majority endorsed development of policy and
      procedures to overcome barriers to FP during CPR.

PMID- 21848047
TI  - Coaching in the cardiovascular surgical population.
AB  - BACKGROUND: More than one quarter of all cardiovascular surgical patients are re
      admitted to hospitals with postoperative complications experienced during the
      first three months of recovery. AIM AND METHOD: The purpose of this discursive
      paper is to review the literature pertaining to a self-management coaching
      intervention that is currently being evaluated using a randomized controlled
      clinical trial. RELEVANCE TO CLINICAL PRACTICE: A discussion of how to integrate
      coaching into clinical practice is presented. The use of coaching in the clinical
      setting has implications for nurses in that it can be used to assess behaviours,
      knowledge, and learning needs; provide individualized education that is
      reflective of a patient's identified learning needs; collaborate with patients in
      setting goals; identify barriers and engage in problem-solving to overcome
      barriers; and create a specific plan for follow-up.

PMID- 21848048
TI  - 2010 resuscitation guidelines update.

PMID- 21848049
TI  - Probiotics and prebiotics: parts of a healthy diet.

PMID- 21848050
TI  - Treating dental sensitivity at home and in the dentist's office.

PMID- 21848051
TI  - Going green in the kitchen: buying locally and seasonally.

PMID- 21848052
TI  - What's new in foot care?

PMID- 21848053
TI  - Treating type 2 diabetes: a growing number of options.

PMID- 21848054
TI  - What your doctor is reading.

PMID- 21848055
TI  - How much do you know about peripheral arterial disease?

PMID- 21848056
TI  - Recipe makeovers. Berry banana smoothie.

PMID- 21848057
TI  - Got fiber?

PMID- 21848058
TI  - Thyroid function tests during first-trimester of pregnancy: a review of
      literature.
AB  - This literature review was conducted to summarize the main points of maternal
      thyroid function tests, with particular attention in the first trimester of
      pregnancy which accompanied with significant biochemical and metabolic
      alteration. The evaluation of thyroid function of either hyperthyroidism and
      hypothyroidism should be assessed by determination of serum Thyroid Stimulating
      Hormone (TSH), Thyroxine (T4), Triiodothyronine (T3), Iodine and Thyroid
      Autoantibodies. Glomerular filtration rate is increased during pregnancy;
      therefor iodine deficiency should be evaluated during the pregnancy to prevent
      hypothyroidism. The role which can be played by Human Chronic Gonadotropin (hCG)
      on stimulating the thyroid gland to become over-active was investigated. Serum
      level ofthyroglobulin (Tg) and Thyroxin Binding Globulin (TBG) should be assessed
      for proper assessments of thyroid gland during pregnancy. Thyroid function tests
      during first-trimester of pregnancy and particularly the reference interval for
      thyroid function tests for pregnant women in each region has to be established,
      to prevent mis-diagnosis and irreversible mental and physical adverse affect for
      growing fetus.

PMID- 21848059
TI  - Applications of the Box-Wilson design model for bio-hydrogen production using
      Clostridium saccharoperbutylacetonicum N1-4 (ATCC 13564).
AB  - Box-Wilson design (BWD) model was applied to determine the optimum values of
      influencing parameters in anaerobic fermentation to produce hydrogen using
      Clostridium saccharoperbutylacetonicum N1-4 (ATCC 13564). The main focus of the
      study was to find the optimal relationship between the hydrogen yield and three
      variables including initial substrate concentration, initial medium pH and
      reaction temperature. Microbial growth kinetic parameters for hydrogen production
      under anaerobic conditions were determined using the Monod model with
      incorporation of a substrate inhibition term. The values of micro(max) (maximum
      specific growth rate) and K, (saturation constant) were 0.398 h(-1) and 5.509 g
      L(-1), respectively, using glucose as the substrate. The experimental substrate
      and biomass-concentration profiles were in good agreement with those obtained by
      the kinetic-model predictions. By varying the conditions of the initial substrate
      concentration (1-40 g L(-1)), reaction temperature (25-40 degrees C) and initial
      medium pH (4-8), the model predicted a maximum hydrogen yield of 3.24 mol H2 (mol
      glucose)(-1). The experimental data collected utilising this design was
      successfully fitted to a second-order polynomial model. An optimum operating
      condition of 10 g L(-1) initial substrate concentration, 37 degrees C reaction
      temperature and 6.0 +/- 0.2 initial medium pH gave 80% of the predicted maximum
      yield of hydrogen where as the experimental yield obtained in this study was
      77.75% exhibiting a close accuracy between estimated and experimental values.
      This is the first report to predict bio-hydrogen yield by applying Box-Wilson
      Design in anaerobic fermentation while optimizing the effects of environmental
      factors prevailing there by investigating the effects of environmental factors.

PMID- 21848060
TI  - Population dynamics of shrimps in littoral marine waters of the Mekong Delta,
      south of Viet Nam.
AB  - The population dynamics of eight commercial species of shrimp (Haliporoides
      sibogae, Harpiosquilla harpax, Metapenaeus affinis, Metapenaeus brevicornis,
      Metapenaeus tenuipes, Parapenaeopsis cultrirostris, Parapenaeopsis gracillima and
      Parapenaeus maxilipedo) distributed in littoral marine zone of the Mekong Delta
      were investigated. Length-based stock assessment using FiSAT II software package
      was used to assess the growth and mortality parameters: Asymptotic size (L8),
      growth coefficient (K), total (Z) and natural (M) mortality, exploitation rate
      (E), recruitment pattern, current probability of capture and selectivity of
      fishing gears. Yield-per-recruit analyses were carried out showing different
      levels of the exploitation. Results showed that the maximum sustainable yield
      would be reached for an exploitation rate higher than the current one for each
      population. However, the size of first capture should be increased for every
      population. The findings indicated that the current exploitations of shrimp
      populations distributed in littoral marine zone of the Mekong Delta are under
      exploitation level for maximum sustainable yield; however, all the shrimp
      populations are subject to growth over-exploitation.

PMID- 21848061
TI  - Extraction and purification of crocin from saffron stigmas employing a simple and
      efficient crystallization method.
AB  - In this study, total crocin was extracted from saffron stigmas using
      crystallization method. Ethanol 80% was selected as the best extraction solvent.
      Crystallization process was carried out in one and two steps at different
      temperatures. Ethanol 80% was used as crystallization medium. Crocin crystals
      obtained from the first crystallization had low purity and thus were subjected to
      the second crystallization. The higher purity crystals were yielded in the second
      crystallization at -5 degrees C. The purity of crocin crystals was studied using
      UV-visible spectrophotometery and HPLC in comparison with Fluka product and
      methanolic extract of saffron stigmas. The results indicated that its purity was
      extremely higher, about 13 times, more than Fluka product. In spite of our
      expectation, the Fluka product was not a pure alpha-crocin sample; five other
      types of crocins in addition to an unknown impurity were seen in its
      chromatogram. The purity of crystallized total crocin in this work was more than
      97%.

PMID- 21848062
TI  - Effect of defoliation and drought stress on yield components and chlorophyll
      content of wheat.
AB  - In order to examine the effects of source restriction and drought stress on yield
      components, flag leaf chlorophyll content and Relative Water Content (RWC) of
      wheat cultivars, a greenhouse experiment was carried out at Shiraz University,
      Shiraz, Iran, during 2009-2010. The wheat cultivars including Shiraz, Bahar,
      Pishtaz, Sistan and Yavaros were sown in 5 kg plastic pots. The source
      manipulation treatments including control (C), defoliation of all leaves (D1),
      defoliation of all leaves except the flag leaf (D2) and defoliation of all leaves
      except the flag leaf and penultimate leaf (D3), were imposed at anthesis. Results
      showed that source restriction decreased number of grain per spike significantly
      in Shiraz cultivar under drought stress condition. Maximum 100-grain weight was
      observed in C treatment of Yavaros and Shiraz under well-watered condition. Among
      the defoliation treatments under drought stress condition, D2 in Pishtaz and D1
      in Shiraz had the highest (3.66 g) and lowest (2.71 g) 100 grain weight,
      respectively. In all cultivars drought stress decreased main shoot yield
      significantly but in Pishtaz and Sistan decreasing rate was less than the other
      cultivars. RWC in Shiraz decreased sharply from 92.1% in well-watered to 66.7%
      (27.5% reduction) under drought stress at 10 DAA. After anthesis, Pishtaz and
      Sistan maintained higher content of flag leaf chlorophyll (from 49.4 to 56.8 SPAD
      unit) under drought stress condition. Generally, selection and culture of
      cultivars that had small responses to defoliation might be a useful strategy in
      yield improvement of wheat in areas where the water availability is low.

PMID- 21848063
TI  - Outcomes of percutaneous pinning in treatment of distal radius fractures.
AB  - Distal radius fractures are among the most common bone fractures all over the
      world. Close reduction and fixation by percutaneous pinning is a less invasive
      method comparing with other open surgeries. This study aims at evaluating the
      functional outcome of this treatment in distal radius fractures. In this
      prospective study, 50 patients with distal radius fractures underwent
      percutaneous pinning during a 16 month period in Tabriz Shohada Hospital. Follow
      up for 3 months was possible in 48 (96%) patients. Possible complications (such
      as infection, nonunion, pin loosening and pain), functional outcomes (including
      range of motion, grip and pinch strengths) and radiological outcome were
      documented in intervals during follow-up. Forty eight patient, 22 males and 27
      females with a mean age of 47.1 +/- 13.7 (19-80) years were enrolled. Local pain,
      infection and pin loosening were documented in 14.6, 16.7 and 2.1% of cases,
      respectively. Based on radiological reports, unacceptable palmar tilt, articular
      step, radial inclination and radial shortening were present in 6.3, 0, 2.1 and
      6.3% of cases, respectively three months post-operation. The clinical outcomes
      according to Cooney's modification of the Green and O'Brien scheme were as
      excellent, good, fair and poor in 52.1, 31.3, 10.4 and 6.3% of cases,
      respectively. According to these results, closed reduction and percutaneous
      pinning of distal radius fractures is a rather successful method with minor
      complications.

PMID- 21848064
TI  - Underlying etiologies of prolonged icterus in neonates.
AB  - The purpose of this study was to determine underlying causes of prolonged
      neonatal icterus. Icterus or jaundice is an important common problem in
      neonatology. When this condition persists beyond 14 days, it is called prolonged
      or protracted neonatal icterus. Determining underlying causes of this problem is
      a pivotal step for management, because a delay in treatment may lead to serious
      complications or even death. In a prospective study, newborns with diagnosis of
      prolonged icterus were evaluated during a six-month period in Tabriz Children
      Teaching Hospital. Data regarding the past medical history, physical examination
      and appropriate laboratory and paraclinical investigations were gathered and
      accordingly, the underlying cause of jaundice was documented. One hundred
      newborns, 67 males and 33 females with a mean age of 21.5 +/- 4.5 days were
      enrolled. Breastfeeding, urinary tract infection, glucose 6-phosphate
      dehydrogenase deficiency and hypothyroidism were found as the main underlying
      causes in 75, 7, 7 and 4% of the cases. The exact etiology was unknown in 4% of
      newborns. ABO incompatibility, sepsis and Down syndrome were underlying
      etiologies in remaining three patients. Present study showed that the underlying
      causes of prolonged neonatal jaundice could be determined in majority of cases
      and breastfeeding is the most common one in this regard.

PMID- 21848065
TI  - Beta-xylanase from Thermomyces lanuginosus and its biobleaching application.
AB  - Thermomyces lanuginosus is thermophilic fungus in which was isolated from
      widespread material. A high number of this fungus was found in composts
      especially mushroom composts. This fungus has been reported to produce a high
      level xylanase when cultivated in the medium containing xylan and corn cob as a
      carbon source. Various strains of T. lanuginosus produced a single xylanase with
      molecular masses in range of 22.0 to 29.0 kDa. Pure beta-xylanase obtained from
      various strains of this fungus exhibited highly stability at high temperature and
      wide pH range. The optimal temperature and optimal pH of pure beta-xylanase from
      various strains of T. lanuginosus have been reported in range of 60-75 degrees C
      and pH 6.0-7.0, respectively. The great thermal stability was resulting from the
      present of hydrophilic amino acid on beta sheet of the surface of xylanase
      structure. Moreover, the relatedness between high and low xylanase producing
      strains can be distinguish by random amplification of polymorphic DNA (RAPD).
      Based on nucleotide sequences and T. lanuginosus xylanase gene has been
      classified to be a member of family 11 (formerly known as cellulase family G)
      glycosyl hydrolases. This enzyme was endo-type xylanase having main product are
      xylose and xylobiose. The expression of xylanase gene from T. lanuginosus was
      achieved in Escherichia coli and methylotrophic yeast Pichia pastoris. The
      ability of T. lanuginosus in which produced large amount of high thermos stable
      xylanase has made this fungus to be a source of xylanase production for
      biobleaching in pulp and paper process.

PMID- 21848066
TI  - Somatosensory evoked potential for detection of subclinical neuropathy in
      Egyptian children with acute lymphoblastic leukaemia.
AB  - To evaluate neurological changes developing during paediatric Acute Lymphoblastic
      Leukaemia (ALL) therapy clinically and through electrophysiological Study of
      Somatosensory Evoked Potentials (SSEPs) changes in different phases of therapy.
      Thirty five-ALL patients with age range from 3-14 years were included compared to
      30 healthy controls. History, neurological examination, complete blood counts,
      cytological examination of bone marrow aspirate and cerebrospinal fluid with
      Measurement of Serum Methotrexate (MTX) were done. The SSEPs were performed and
      patients subjected to another SSEP with measurement of serum MTX level before and
      10 days after intra-thecal injection (IMTX). Clinical neurological findings in
      patients after induction were depressed deep tendon reflexes (43.3%), hypotonia
      (28.6%), lost pain sensation (28.6%), muscle weakness (17.1%) and movement
      disorders (17.1%). Percentage of delayed SSEPs after induction were at levels of
      brachial plexus (28.6%), spinal cord (68.6%), cortical conduction (31.4%), ERB
      N13 Inter Peak Latency (IPL) (74.3%) and N13-N20 IPL (17.1%) in the studied
      patients. Significant prolonged latency of N13 (p = 0.005), N20 (p = 0.04) and
      IPL of ERB-N 13 (p = 0.005), N13-N20 (p = 0.01), Inter-Side Difference (ISD) of
      N13 (p = 0.01), ERB-N13 (p = 0.02) and N13-N20 (p = 0.03) after induction
      compared to values at diagnosis. Significant positive correlation were found
      between serum MTX after IMTX with N13-N20 IPL (p = 0.01), N20 ISD (p = 0.03) with
      significant prolongation in N20 latency, N13-N20 IPL and ISD of N20 compared to
      values before injection. ALL patients have prolonged latency of SSEPs at cervical
      cord and cortical levels which increased after IMTX due to axonal injury
      throughout the cord. SSEPs could be an early diagnostic tool for subclinical
      neuropathy.

PMID- 21848067
TI  - Antioxidant activity of oak (Quercus) leaves infusions against free radicals and
      their cardioprotective potential.
AB  - The aim of present study was to evaluate antioxidant capacity and
      cardioprotective potential of leaves infusions and partially purified fractions
      of Quercus sideroxyla and Q. eduardii (red oaks) and Q. resinosa (white oak).
      Consumption of polyphenol-rich beverages derived from plants, such as oak may
      represent a beneficial diet in terms of cardiovascular protection. Infusions from
      Oak leaves were obtained and probed for total phenolics by Folin-Ciocalteu, DPPH
      and hydroxyl radicals scavenging by DPPH test and Deoxy-D-ribose method, the
      antioxidant capacity was evaluated by FRAP and ORAC tests, inhibitions of Low
      Density Lipoproteins (LDL) oxidation and Angiotensin Converting Enzyme (ACE)
      activity were measured. A HPLC analysis was performed by HPLC-MS. Bioactive
      polyphenols such as gallic and ellagic acids, catechin, quercetin and
      derivatives: naringenin and naringin were detected in Quercus infusions. A
      distinctive HPLC profile was observed among the red and white oak samples. Q.
      resinosa infusions have exhibited the highest antioxidant activity in comparison
      with the other species, although in the inhibition of LDL oxidation no
      differences were observed. In the inhibition of the ACE, Q. resinosa was more
      effective (IC50, 18 ppm) than Q. sideroxyla, showing same effect as the control
      Captopril. From the results it is possible to postulate that not only chelating
      activity is important in these infusions, especially in Q. resinosa.

PMID- 21848068
TI  - Optimization of culture medium to increase the production of desferrioxamine B
      (Desferal) in Streptomyces pilosus.
AB  - The aim of this study was optimization of culture medium in direction of
      increasing the production rate of desferrioxamine B. Streptomycetes are the most
      widely studied and well known genus of the actinomycete family. Streptomycetes
      usually inhabit soil and are important decomposers. The genus Streptomyces are
      Gram-positive and GC rich bacteria that are important for production of many
      antibiotics and secondary metabolites. These metabolites are important in
      industrial and medical fields. Deferoxamines (also known as desferrioxamine B,
      desferoxamine B, DFO-B, DFOA, DFB or desferal) are low-molecular-weight, iron
      chelating compounds (siderophores) produced and secreted by many actinomycetes,
      including species of Streptomyces, Nocardia and Micromonospora. Streptomyces
      pilosus synthesizes the siderofore desferrioxamine B. Desferrioxamine B is used
      clinically to treat disorders related to iron overload and pathological iron
      deposition in human. Our results revealed that the use of soybean as a base
      medium plus additives such as Na2HPO4.12H2O, NaH2PO4, MgSO4.7H2O, ZnSO4.7H2O,
      FeSO4.7H2O, CaCl2.2H2O, NaCl, MnSO4, NH4Cl, KH2PO4, K2HPO4, some of the amino
      acids and vitamins increased the production of desferrioxamine B about 8 times in
      comparison with the control.

PMID- 21848069
TI  - The efficiency of Amberjet 4200 resin in removing nitrate in the presence of
      competitive anions from Shiraz drinking water.
AB  - The aim of this research is to study the feasibility of removing nitrates from
      water by means of anion exchange. In the purposed work an attempt was made to
      utilize strong basic anion resin to remove nitrate in the presence of competitive
      anion. Amberjet Cl- 4200 ion exchange resin was used in a batch scale. The
      fixation rate of nitrate without the presences of any competitive anion was
      almost constant (94.60-96.43) when the nitrate concentrations are in the range of
      100-150 mg L(-1). The fixation rate of nitrate in the presences of two
      competitive anions (sulphate and chloride) was reduced to 82% when the
      concentration of nitrate was 100 mg L(-1).

PMID- 21848070
TI  - The state of serum lipids profiles in sub-clinical hypothyroidism: a review of
      the literature.
AB  - Thyroid disorders usually associated with lipid abnormalities. Overt
      hypothyroidism is a state with thyroid hormone deficiency. Sub clinical
      hypothyroidism is defined as condition, in which thyroid stimulating hormone
      concentration elevated when serum thyroid hormones are at normal levels. Whether
      sub-clinical hypothyroidism associated with lipid alteration, it is the main
      concept behind this study. Although, in this study, we found cases with normal
      thyroxin and elevated thyroid stimulating hormone are common, but whether the sub
      clinical hypothyroidism finally converted to overt hypothyroidism are not
      universally accepted. The findings also indicated subjects with sub-clinical
      hypothyroidism usually are accompanied with dyslipidemia and in general the total
      cholesterol level is higher among sub-clinical hypothyroid patients, with
      eventual risk of arthrosclerosis. This study indicated that there is not a common
      findings to support the benefit of thyroxin therapy in sub-clinical
      hypothyroidism. It is concluded that it seems sub-clinical hypothyroidism is a
      common thyroid abnormality which can be diagnosed by the medical diagnostic
      laboratory through thyroid function test and it is mainly accompanied with lipid
      disorder.

PMID- 21848071
TI  - Silymarin ameliorates cisplatin-induced hepatotoxicity in rats: histopathological
      and ultrastructural studies.
AB  - The benefit of silymarin, a plant extract with strong antioxidant activity
      against hepatotoxicity induced by cisplatin in rats was investigated in this
      study. Cisplatin is one of the most effective chemotherapeutic drugs, yet it
      alone does not achieve a satisfactory therapeutic outcome and at high doses it
      can produce undesirable side effects. Five equal-sized groups (18 rats each) of
      male Sprague Dawley rats [control, vehicle; cisplatin; silymarin 2 h after
      cisplatin injection; and silymarin 2 h before cisplatin injection] were used.
      Histopathological and ultrastructural observation of livers were carried out
      using light and electron microscopy. Results documented that cisplatin produced
      behavioral, external features animal changes, as well as hazard pathological
      picture changes in liver where most hepatocytes appeared diminutive with
      vacuolated cytoplasm, sinusoids dilated and organelle disorganized. These results
      revealed that cisplatin may be toxic and terminates in complex liver damage.
      Administrations of silymarin 2 h after cisplatin, significantly increase the body
      weight returning it to normal, yet it failed in complete protection against the
      pathological alteration caused by cisplatin. Pretreatment with silymarin 2 h
      before cisplatin significantly decreased the pathological changes induced by
      cisplatin and appeared highly protective. These results suggested that silymarin
      possess protective effects against cisplatin hepatotoxic action in animal models.
      Since, no significant toxicity of silymarin is reported in human studies, this
      plant extract can be used as a dietary supplement by patients taking
      anticancerous medications and might serve as a novel combination agent with
      cisplatin since it plays a significant role in reducing its toxicity.

PMID- 21848072
TI  - Study of some factors of conservation of pollens of two plant species
      (Callistemon rigidus and Hymenocardia acida) of bee flora of Adamawa (Cameroon).
AB  - To contribute to the preservation of the bee flora of Adamawa, a study to
      determine the optimal conditions for preservation of Callistemon rigidus and
      Hymenocardia acida pollens, two endangered bee species, was conducted from March
      2006 to March 2007 in this region. The study began by anthers collection at the
      experimental site and they were brought to the laboratory where fresh pollens are
      collected and undergo in vitro germination and storage tests. These tests have
      required the installation of two solidified media culture: Brewbaker and Kwack
      (BK) and Heslop-Harrison (HH) media to evaluate pollens germination under the
      influence of some physiological factors and assess the influence of storage at +
      10 and -20 degrees C with and without initial drying. The results show that
      sucrose concentrations of 10 and 15% on BK medium has produced respectively 60.69
      +/- 3.1 and 04.49 +/- 0.21% as the highest values of germination percentage in
      Callistemon rigidus and Hymenocardia acida. Temperatures of 30 and 25 degrees C
      which produced 60.69 +/- 2.53 and 04.25 +/- 0.29% of germination and pH 5 with
      55.14 +/- 4.14% and 6.8 with 04.54 +/- 0.6% were respectively favourable in the
      same order for the germination of both species of pollens. Time for a week of
      drying allowed the extension of storage time of both species of pollens as from
      +10 to -20 degrees C. The Callistemon rigidus pollens were generally more
      tolerant to the storage at-20 degrees C showing the critical period of storage
      exceeding 22 weeks while those of Hymenocardia acida were less tolerant to both
      temperatures with most critical period of storage established to 8 weeks.

PMID- 21848073
TI  - Ugba, the fermented African oilbean seeds; its production, chemical composition,
      preservation, safety and health benefits.
AB  - Ugba is the Ibo name of the fermented African Oilbean seeds (Pentaclethra
      macrophylla, Benth). It is a traditional food condiment generally produced by
      natural (local) fermentation in homes as a small family business. It is an
      important and cheap source of protein for people whose staple foods are deficient
      in proteins. It is also eaten as a delicacy and used as flavouring for soup. This
      write up aims to review all published studies on ugba in the direction of the
      various methods used in the production, the chemical composition of the seeds,
      the microorganisms involved and the biochemical changes that occur during
      fermentation and optimization of the fermentation. The nutritional and food
      values, toxicological properties, health promoting potentials, microbiological
      safety as well as the storage and preservation have also been highlighted.

PMID- 21848074
TI  - Role of bacteria isolates in the spoilage of fermented African oil bean seed
      ugba.
AB  - Study was carried out to determine the spoilage association of traditionally
      fermented ugba, product of African oil bean seed. Samples were collected from
      three markets within Enugu metropolis in Eastern Nigeria. Microbial population of
      ugba was isolated, characterized and identified. Effect of time on product
      quality, total viable cell count and individual growth pattern of isolates was
      evaluated. Microorganisms isolated were Proteus sp., Klebsiella sp.,
      Staphylococcus epidermidis, E. coli, Bacillus licheniformis and Bacillus
      subtilis. Initial viable cell count increased from 4.6 x 10(8) -6.2 x 10(8), 6.0
      x 10(9) -6.9 x 10(9) and 3.9 x 10(8) -5 x 10(8) cfu g(-1) by the 4th day for
      samples from Mayor, Kenyatta and Garki markets, respectively. Organoleptic
      changes in texture and colour were seen to be a factor of time of storage. A
      decline in growth of Proteus sp., E. coli, Klebsiella sp. and S. epidermidis by
      the 4th day of storage was observed for all samples. Viable cells of B.
      licheniformis increased from 6.1 x 10(7) -17.7 x 10(7) cfu g(-1), 13.9 x 10(8) 
      20.0 x 10(8) and 8.7 x 10(7) -15.5 x 10(7) by the 4th day of storage for samples
      from Mayor, Kenyatta and Garki markets respectively. Growth of B. subtilis
      increased from 9.2 x 10(7) -19.9 x 10(7), 14.9 x 10(8) -21.2 x 10(8) and 11.5 x
      10(7) -17.2 x 10(7) cfu g(-1) for samples from Mayor, Kenyatta and Garki markets
      respectively. Our results indicate that ugba spoilage is primarily a result of
      the continued activity of African oil bean seed fermentative organisms B.
      subtilis and B. licheniformis.

PMID- 21848075
TI  - Improved production of L-lysine by over-expression of Meso-diaminopimelate
      decarboxylase enzyme of Corynebacterium glutamicum in Escherichia coli.
AB  - The aim of this study is over-expression of Meso-diaminopimelate decarboxylase
      enzyme (EC 4.1.1.20) and enhancement of L-lysine production rate. The C.
      glutamicum LysA gene which encodes a Meso-diaminopimelate decarboxylase was
      cloned in E. coli. The cloned gene was sequenced; it encodes a 445 amino acids
      protein with molecular weight of 47 kD. Expression of the LysA gene in E. coli
      resulted in an increase in Meso-diaminopimelate decarboxylase activity,
      correlated with the presence in sodium dodecyl sulfate-polyacrylamid gels of a
      clear protein band that corresponds to this enzyme. The induction of cloned gene
      by IPTG has been shown to have an inhibitory effect on cell growth due to over
      expression of the cloned gene. A two fold increase in lysine production rate was
      observed after introduction of the cloned gene into E. coli.

PMID- 21848076
TI  - Comparison between invasive and noninvasive tests in diagnosis of Helicobacter
      pylori infection.
AB  - In this study, the invasive and noninvasive diagnotic tests were compared to
      choose the appropriate test for diagnostice of H. pylori infection. Helicobacter
      pylori (H. pylori) is a human pathogen that causes chronic gastritis, has a role
      in gastric and duodenal ulcer, is involved in gastric carcinogenesis and is
      regarded as a possible important factor in at least a subset of patients with
      functional dyspepsia. The diagnosis of H. pylori is an essential element in the
      management of many common gastrointestinal pathologies. The assessment of each
      routine invasive and noninvasive test is important. We studied a total of 127
      outpatients for the detection of H. pylori infection. The presence of H. pylori
      infection by invasive tests containing the Rapid Urease Test (RUT), histology
      (Giemsa staining) and culture in 127 patients. Patients who were positive in
      culture, or two tests from four tests, invasive and noninvasive, were considered
      to have H. pylori infection. In noninvasive tests, we evaluated anti-H. pylori
      IgG and anti-CagA antibodies using commercial Enzyme-Linked Immunoassay (ELISA)
      and Western blot in dyspeptic patients. Eighty five out of the 127 patients were
      positive for H. pylori. Helicobacter pylori IgG seropositivity and 35 out of the
      127 patients were positive for immunoblot. RUT had sensitivity, specifity and
      accuracy of 96, 80 and 90.5%, respectively; for Elisa these were 85.2, 33 and
      70.5%, respectively and for ELISA with immunoblotting they were 65, 45 and 58.8%,
      respectively. The results of this study suggest that noninvasive tests (ELISA,
      immunoblotting) have the lowest and RUT with histology have the highest accuracy.
      These earlier tests can not be used for accurate infection diagnosis.

PMID- 21848077
TI  - Speaking rate affects the perception of duration as a suprasegmental lexical
      stress cue.
AB  - Three categorization experiments investigated whether the speaking rate of a
      preceding sentence influences durational cues to the perception of suprasegmental
      lexical-stress patterns. Dutch two-syllable word fragments had to be judged as
      coming from one of two longer words that matched the fragment segmentally but
      differed in lexical stress placement. Word pairs contrasted primary stress on
      either the first versus the second syllable or the first versus the third
      syllable. Duration of the initial or the second syllable of the fragments and
      rate of the preceding context (fast vs. slow) were manipulated. Listeners used
      speaking rate to decide about the degree of stress on initial syllables whether
      the syllables' absolute durations were informative about stress (Experiment Ia)
      or not (Experiment Ib). Rate effects on the second syllable were visible only
      when the initial syllable was ambiguous in duration with respect to the preceding
      rate context (Experiment 2). Absolute second syllable durations contributed
      little to stress perception (Experiment 3). These results suggest that speaking
      rate is used to disambiguate words and that rate-modulated stress cues are more
      important on initial than noninitial syllables. Speaking rate affects perception
      of suprasegmental information.

PMID- 21848078
TI  - Temporal variability and stability in infant-directed sung speech: evidence for
      language-specific patterns.
AB  - In this paper, sung speech is used as a methodological tool to explore temporal
      variability in the timing of word-internal consonants and vowels. It is
      hypothesized that temporal variability/stability becomes clearer under the
      varying rhythmical conditions induced by song.This is explored
      crosslinguistically in German - a language that exhibits a potential vocalic
      quantity distinction - and the non-quantity languages French and Russian. Songs
      by non-professional singers, i.e. parents that sang to their infants aged 2 to 13
      months in a non-laboratory setting, were recorded and analyzed.Vowel and
      consonant durations at syllable contacts of trochaic word types with CVCV or
      CV:CV structure were measured under varying rhythmical conditions. Evidence is
      provided that in German non-professional singing, the two syllable structures can
      be differentiated by two distinct temporal variability patterns: vocalic
      variability (and consonantal stability) was found to be dominant in CV:CV
      structures whereas consonantal variability (and vocalic stability) was
      characteristic for CVCV structures. In French and Russian, however, only vocalic
      variability seemed to apply.Additionally, findings suggest that the different
      temporal patterns found in German were also supported by the stability pattern at
      the tonal level. These results point to subtle (supra) segmental timing
      mechanisms in sung speech that affect temporal targets according to the specific
      prosodic nature of the language in question.

PMID- 21848079
TI  - Processing of no-release variants in connected speech.
AB  - The cross modal repetition priming paradigm was used to investigate how potential
      lexically ambiguous no-release variants are processed. In particular we focus on
      segmental regularities that affect the variant's frequency of occurrence (voicing
      of the critical segment) and phonological context in which the variant occurs
      (status of the following word-initial segment). Primes consisted of carrier words
      ending in a segment likely (voiced; e.g., BAND) or unlikely (voiceless; PLANT) to
      be produced in no-release form followed by a consonant or vowel onset context
      word. Each carrier word had an embedded lexical competitor (embedded word) formed
      by the segments prior to its final consonant (e.g., plan in plant). Productions
      of these embedded words (true embedded word) were also used as primes. Both true
      embedded words (Experiments Ia-Ic) and carrier words (Experiments 2a-2c) were
      used as visual targets.The results are discussed in terms of the contribution of
      probabilistic speech events to theories of spoken word recognition and lexical
      competition.

PMID- 21848080
TI  - Polynomial modeling of child and adult intonation in German spontaneous speech.
AB  - In a data set of 291 spontaneous utterances from German 5-year-olds, 7-year-olds
      and adults, nuclear pitch contours were labeled manually using the GToBI
      annotation system.Ten different contour types were identified.The fundamental
      frequency (F0) of these contours was modeled using third-order orthogonal
      polynomials, following an approach similar to the one Grabe, Kochanski, and
      Coleman (2007) used for English. Statistical analyses showed that all but one
      contour pair differed significantly from each other in at least one of the four
      coefficients.This demonstrates that polynomial modeling can provide quantitative
      empirical support for phonological labels in unscripted speech, and for languages
      other than English. Furthermore, polynomial expressions can be used to derive the
      alignment of tonal targets relative to the syllable structure, making polynomial
      modeling more accessible to the phonological research community. Finally, within
      contour comparisons of the three age groups showed that for children, the
      magnitude of the higher coefficients is lower, suggesting that they are not yet
      able to modulate their pitch as fast as adults.

PMID- 21848081
TI  - Articulation rate in childhood and adolescence: Hebrew speakers.
AB  - This study aimed to quantify articulation rate among Hebrew speaking children and
      adolescents across a wide age range, and to assess whether age-related
      differences vary according to metric. One hundred and forty children, in seven
      age groups, participated in this cross-sectional study. All children were
      recorded during conversation and a picture description task, and articulation
      rate was measured using three metrics: word per minute (WPM), syllable per second
      (SPS) and phone per second (PPS). A significant increase in articulation rate was
      observed with age. Rate measurements during conversation were significantly
      faster than in picture description, and no gender differences were found. In
      general, the SPS and PPS metrics yielded equivalent results, which were different
      from those obtained with the WPM metric. Articulation rate among normally fluent
      children and adolescents increased with age. Furthermore, an increase in rate was
      evident after the age of 13 years.

PMID- 21848082
TI  - Perception of Japanese temporally-cued contrasts by American English listeners.
AB  - American listeners' perception of Japanese contrasts of vowel length (e.g., kiro
      vs. kiiro), consonant length (e.g., kite vs. kitte) and syllable number/length
      (e.g., k(j)oo vs. kijoo) was examined. Stimuli consisted of sentence-length
      utterances produced by a native Japanese talker; five minimal pairs of each
      contrast type were included. Questions were: a) can American listeners with no
      Japanese experience discriminate these contrasts, b) are there differences in
      relative difficulty of the three contrast types, and c) do instructions and other
      task variables affect performance accuracy? A categorial AXB discrimination task
      was used in two studies: Study I tested the three contrast types presented in
      separate blocks with detailed instructions about what to listen for; Study 2
      tested the contrast types presented randomly intermixed with no specific
      instructions about the nature of the contrasts. Results indicated that naive
      American listeners could discriminate all three contrast types well above chance,
      and that there were no significant overall differences in relative difficulty
      across contrast types. Performance was significantly poorer in Study 2 where
      listeners' attention had not been directed to the nature of the contrasts. In
      both studies, there was significant and large variability in accuracy across
      different minimal pairs of each contrast type.

PMID- 21848083
TI  - An EPG study of palatal consonants in two Australian languages.
AB  - This study presents EPG (electro-palatographic) data on (alveo-)palatal
      consonants from two Australian languages, Arrernte and Warlpiri. (Alveo-)palatal
      consonants are phonemic for stop, lateral and nasal manners of articulation in
      both languages, and are laminal articulations. However, in Arrernte, these lamino
      (alveo-)palatals contrast with lamino-dental consonants for all three manners of
      articulation (i.e., it is a double-laminal language), whereas in Warlpiri this
      laminal contrast does not exist (i.e., it is a single-laminal language). Data are
      analyzed according to manner of articulation, vowel context and phrase position.
      Results suggest that in the double-laminal languageArrernte,the (alveo-)palatal
      articulation is further back than in the single-laminal language Warlpiri,
      presumably due to the presence of the lamino-dental in theArrernte phoneme
      inventory. The lateral has the least contact in the back regions of the palate
      for both languages, but there is no significant difference in contact pattern
      between the stop and the nasal. However, results tentatively suggest that the
      nasal (alveo-)palatal is the most likely to show effects of prosodic or vocalic
      context, and it is suggested that this is due to the less strict airflow
      requirements for the nasal than for the stop or the lateral.

PMID- 21848084
TI  - Paying it forward: on mentors and mentoring.

PMID- 21848085
TI  - Social work interest in prevention: A content analysis of the professional
      literature.
AB  - Every day in the United States, over halfa million social workers provide
      services to people with health, mental health, and substance abuse problems in a
      fragmented system that emphasizes disease treatment over prevention. Powerful
      issues--including health inequities, population aging, globalization, natural
      disaster, war, and economic downturn--make the need for preventive approaches
      more critical than ever. Despite social work's historic commitment to enhancing
      human well-being and public health involvement, little is known about how social
      work currently views prevention or whether it is being addressed in the social
      work professional literature. To determine whether, and to what extent,
      prevention is addressed, discussed, and published in social work journals, the
      authors--all public health social work researchers-undertook a content analysis
      of nine peer-reviewed journals, analyzing all articles published from 2000 to
      2005. A total of 1,951 articles were reviewed and coded for prevention according
      to specified criteria. A relatively small number--109 (5.6 percent)--were found
      to meet the criteria for being a prevention article, suggesting that prevention
      is still a minority interest area within social work.A renewed conversation about
      prevention in social work can enhance opportunities for strong social work
      participation in the transdisciplinary collaboration needed in this new era of
      health reform.

PMID- 21848086
TI  - Spiritual assessment and Native Americans: establishing the social validity of a
      complementary set of assessment tools.
AB  - Although social work practitioners are increasingly likely to administer
      spiritual assessments with Native American clients, few qualitative assessment
      instruments have been validated with this population. This mixed-method study
      validates a complementary set of spiritual assessment instruments. Drawing on the
      social validity literature, a sample of experts in Native culture (N = 50)
      evaluated the instruments' cultural consistency, strengths, limitations, and
      areas needing improvement. Regarding the degree of congruence with Native
      American culture, verbally based spiritual histories ranked highest and
      diagrammatically oriented spiritual genograms ranked lowest, although all
      instruments demonstrated at least moderate levels of consistency with Native
      culture.The results also suggest that practitioners' level of spiritual
      competence plays a crucial role in ensuring the instruments are operationalized
      in a culturally appropriate manner.

PMID- 21848087
TI  - Federal funding of social work research: high hopes or sour grapes?
AB  - Placed in the historical context of government funding ofacademic research, this
      critical analysis identifies the complexities and implications of schools of
      social work pursuing federal grants for research. Schools of social work with
      particular organizational characteristics are better able to compete for federal
      grants, incurring lower opportunity costs than others. The low probability of
      grant success for most schools, the organizational adaptations needed for
      success, and the narrow epistemology of many funding programs call into question
      whether federal funding of research should be considered the sine qua non for
      academic social work.

PMID- 21848088
TI  - Multiracial competence in social work: recommendations for culturally attuned
      work with multiracial people.
AB  - According to the 2010 U.S. census, approximately 9 million individuals report
      multiracial identities. By the year 2050, as many as one in five Americans could
      claim a multiracial background. Despite this population growth, a review of
      recent empirical and theoretical literature in social work suggests a
      disproportionate lack of attention to issues ofmultiraciality. Instead, social
      work practice models remain embedded in traditional societal discourses of race
      and culture that often exclude or marginalize the experiences of multiracial
      individuals and families.This article summarizes recommendations following the
      domains of awareness, knowledge, and skills in the NASW Standards for Cultural
      Competence in Social Work Practice to support culturally attuned social work
      practice with multiracial people. The authors argue that a culturally attuned
      practice approach--one that is inclusive of multiraciality--is not only timely,
      but also consistent with the profession's ethical obligation to provide
      culturally relevant services to all consumers and clients.

PMID- 21848089
TI  - Empowering staff and clients: comparing preferences for management models by the
      professional degrees held by organization administrators.
AB  - In this article, findings from a national survey of social service managers are
      described. Respondents were asked to identify theories and models of management
      that influenced their administrative activities. The results indicate that many
      of the respondents used an empowerment-oriented approach to management.
      Respondents were more likely to engage in management activities that focused on
      empowering staffthan in activities intended to increase client involvement in the
      political process or organizational decision making. However, when the responses
      of participants with MSW degrees were compared with those of non-social workers,
      findings indicate that social workers are more likely to engage in workplace
      activities that facilitate the political empowerment of clients.

PMID- 21848090
TI  - Burnout and physical health among social workers: A three-year longitudinal
      study.
AB  - The high risk of burnout in the social work profession is well established, but
      little is known about burnout's impact on the physical health of social workers.
      This article examines the relationship between burnout and physical health, using
      data from a longitudinal study of social workers. California-registered social
      workers (N = 406) were surveyed annually over a three-year period. Using
      structural equation modeling, the authors conducted a path analysis to test
      whether burnout predicted changes in physical health over time.The results showed
      that social workers with higher initial levels of burnout later reported more
      physical health complaints. Moreover, higher levels of burnout led to a faster
      rate of deterioration in physical health over a one-year period.The potential
      implications for policy and social service organizations are discussed.

PMID- 21848091
TI  - Factors influencing the general well-being of low-income Korean immigrant elders.
AB  - This study explores factors that influence the general well-being (anxiety,
      depression, positive well-being, self-control, vitality, and general health) of
      low-income Korean immigrant elders by interviewing 206 older adults living in Los
      Angeles County and Orange County, California. Ordinary least squares regression
      results reveal that lack of English proficiency and longer residence in the
      United States were significant predictors of higher anxiety, higher
      depression,lower self-control,lower vitality, and lower general health among
      Korean immigrant elders. Losing a spouse was a significantly negative factor in
      vitality. Financial problems were significantly associated with lower positive
      well-being. Social support was a significant factor in lower anxiety, lower
      depression, higher positive well-being, higher self-control, and higher vitality.
      Spiritual coping was significantly associated with lower anxiety,lower
      depression, higher positive well-being, and higher vitality. The findings of this
      study show that low-income Korean immigrant elders are at high risk for
      psychological and physical health problems influenced by difficulties with the
      acculturation or adjustment and socioeconomic stress of living in a new society.
      The study discusses essential implications for culturally competent social work
      practice among low-income Korean immigrant elders.

PMID- 21848092
TI  - Is social work a human rights profession?

PMID- 21848093
TI  - Reconciling evidence-based practice, evidence-informed practice, and practice
      based research: the role of clinical data-mining.

PMID- 21848094
TI  - Re-engineering the coding workflow: assessing today with an eye toward tomorrow.
AB  - EHRs, CAC, ICD-10--coding is in the midst of profound change. Which makes this
      the best time to re-engineer coding workflow. Five steps help HIM professionals
      assess and evolve coding workflows with an eye toward tomorrow.

PMID- 21848095
TI  - Stop payment: CMS prohibits Medicaid payments on "healthcare-acquired
      conditions".

PMID- 21848096
TI  - Conducting a charge description master audit: getting the most value from an
      internal review.
AB  - Periodic audits of the charge description master are a key piece of an
      organization's compliance program. But they can do more than verify compliance-
      they can help improve the business.

PMID- 21848097
TI  - Documenting occupational history: the value to patients, payers, and researchers.
AB  - Recording patient work history is vital to identifying work-related injuries and
      illnesses. As electronic health records become widespread, this is an important
      time to ensure occupational health data elements are included in EHR standards.

PMID- 21848098
TI  - Access report: OCR tries subtraction through addition in accounting of disclosure
      rule.

PMID- 21848099
TI  - Managing physician queries in the EHR.

PMID- 21848100
TI  - LOINC as a data standard: how LOINC can be used in electronic environments.

PMID- 21848101
TI  - EHRs in the cloud: contract protection for a rainy day.

PMID- 21848102
TI  - Understanding governmental audits.

PMID- 21848103
TI  - Coding for external causes of morbidity in ICD-10-CM.

PMID- 21848105
TI  - ICD-10--the new teacher's pet.

PMID- 21848104
TI  - Preparing for the CAC transition.

PMID- 21848106
TI  - The editor's offering.

PMID- 21848107
TI  - The president's page.

PMID- 21848108
TI  - Changes in oxygenation in mechanically ventilated critically ill patients
      following hyperbaric treatment.
AB  - BACKGROUND: Some ventilated intensive care unit (ICU) patients may experience
      reduced oxygenation following hyperbaric oxygen treatment (HBOT). METHODS: In a
      prospective, single-centre, observational study, we documented changes in
      oxygenation and the need for associated changes in ventilator settings in 25
      consecutive, mechanically ventilated ICU patients immediately post-treatment and
      1, 2, 3 and 6 hours following 61 HBOT sessions. The primary outcome measure of
      oxygenation was the ratio of arterial partial pressure of oxygen (P(a)O2) against
      the level of inspired oxygen (F(i)O2), P(a)O2/F(i)O2. RESULTS: Following HBOT,
      the P(a)O2/F(i)O2 ratio decreased by 27% on return to ICU (P < 0.001, 95%
      confidence intervals (CI) 20.6 to 34.2); 22% at 1 hour post-HBOT (P < 0.001, 95%
      CI 15.1 to 28.6); and 8% at 2 hours post (P = 0.03, 95% CI 0.8 to 14.4). The
      ratio showed no significant differences from pre-HBOT at 3 and 6 hours post-HBOT.
      P(a)O2/F(i)O2 ratio changes necessitated adjustments to ventilation parameters
      upon return to ICU following 30 of 61 HBOT sessions in 17 out of the 25 patients.
      The most common ventilation parameter altered was F(i)O2 (n = 20), increased by a
      mean of +0.17 (95% CI 0.11 to 0.23) above baseline for two hours following HBOT.
      CONCLUSIONS: Following HBOT, oxygenation is reduced in a majority of mechanically
      ventilated ICU patients and requires temporary alterations to mechanical
      ventilation settings. Further study to identify predictive characteristics and to
      determine causation for those at risk of needing ventilation alterations is
      required.

PMID- 21848109
TI  - Transportation of divers with decompression illness on the west coast of
      Scotland.
AB  - INTRODUCTION: There is a time line for divers who develop decompression illnesses
      (DCI) from the completion of their dive to the initiation of recompression. The
      time to treatment is influenced by many factors; two being the time before
      acknowledgement that the diver has a pressure-related illness and the time taken
      for transfer from that point to commencment of recompression. METHOD: Time to
      onset of symptoms, and time from onset of symptoms to treatment were analysed for
      233 divers, 202 recreational and 31 professional, presenting within 24 h of onset
      of symptoms to the Dunstaffnage Hyperbaric Unit between 1990 and 2009, who were
      transported by air, sea or road. RESULTS: Divers with severe DCI had
      significantly shorter times for onset of symptoms (95% confidence intervals 0.9
      to 2.3 h longer for mild/moderate compared to severe DCI) and were transferred
      for treatment approximately twice as fast as those with mild/moderate symptoms
      (inter-quartile ranges: recreational divers, 2.25-5.63 h for mild/moderate DCI
      versus 1.54-3.25 h for severe DCI; professional divers, 2.63-11.13 h for
      mild/moderate DCI versus 2.25-2.92 h for severe DCI). Although choice of
      transport was most likely influenced both by location and disease severity,
      transfer modality did not significantly affect time to treatment for divers with
      severe DCI. In addition, no differences in time to treatment were observed
      between professional and recreational divers irrespective of disease severity.
      CONCLUSIONS: The data suggest that transport was optimised to fit the particular
      circumstances of the patient and that divers treated for DCI in Scotland may
      benefit from there being a single, integrated, co-ordinated clinical service.

PMID- 21848110
TI  - Provisional report on diving-related fatalities in Australian waters 2006.
AB  - INTRODUCTION: An individual case review of diving-related deaths reported as
      occurring in Australia in 2006 was conducted as part of the Divers Alert Network
      Asia-Pacific (DAN AP) dive fatality reporting project. METHOD: The case studies
      were compiled using reports from witnesses, the police and coroners. In each
      case, the particular circumstances of the accident and details from the post
      mortem examination, where available, are provided. RESULTS: In total, there were
      16 reported fatalities (eight fewer than 2005), all involving males. Ten deaths
      occurred while snorkelling and/or breath-hold diving and six while scuba diving,
      one of which involved the use of a closed-circuit rebreather. One death resulted
      from an encounter with a stingray and two involved scuba divers diving alone
      after an extended absence from diving. Cardiac-related issues were thought likely
      to have contributed to the deaths of six snorkel divers and one scuba diver.
      CONCLUSIONS: Trauma from a marine creature, snorkelling or diving alone and pre
      existing medical conditions once again featured in several deaths in this series.

PMID- 21848111
TI  - Risk factors for running low on gas in recreational divers in Western Australia.
AB  - INTRODUCTION: The aim of this study was to investigate risk factors associated
      with running low on gas among certified recreational divers. METHODS: Dive and
      diver information were collected from divers joining organised recreational dives
      in Western Australia and depth/time loggers were attached to each diver. Case
      dives ending with < 50 bar in the cylinder were compared with control dives made
      at the same dive site and time by divers with > or = 50 bar remaining. A
      conditional logistic regression model identified factors significantly associated
      with running low on gas. RESULTS: In total, 1,032 dive profiles were collected.
      Case dives (n = 183) returning with < 50 bar were compared with 510 control dives
      ending with > or = 50 bar. Perceived workload was associated with rate of
      consumption of gas. Factors associated with a dive ending low on gas included:
      younger age; males; lower number of lifetime dives; a longer period since last
      dive; deeper maximum depth and breathing at a heavier rate. Eleven per cent of
      case divers, compared with 1% of control dives, reported surprise at the low
      remaining level of gas. CONCLUSIONS: Dive organisers are recommended to select
      dive sites based on the recent experience of the group and to encourage divers to
      monitor their remaining gas frequently, relative to the depth of the site. Divers
      are reminded that, if they perceive a strenuous workload, they should pay even
      closer attention to monitoring their gas reserves. That 89% of low-on-gas dives
      were reported to be no surprise to the divers making them warrants further
      investigation.

PMID- 21848112
TI  - Solid-state electrolyte sensors for rebreather applications: a preliminary
      investigation.
AB  - INTRODUCTION: Recently developed prototypes of zirconium dioxide and NASICON
      based micro solid-state electrolyte oxygen (O2) and carbon dioxide (CO2) sensors
      were tested for their potential suitability in rebreathers. The O2 sensor has a
      quasi-indefinite lifetime, whilst that of the CO2 sensor is approximately 700 h.
      This is a preliminary report of a new technological application. METHODS: The O2
      sensor was tested in a small pressure chamber to a partial pressure of oxygen
      (PO2) of 405 kPa (4 bar). The CO2 sensor was tested up to 10 kPa CO2. The
      response times to a step change of pressure were measured, and cross-sensitivity
      for helium tested using trimix. A rebreather mouthpiece was modified so that
      breath-by-breath gas recordings could be observed. Power consumption to heat the
      sensors was measured. RESULTS: The O2 sensor demonstrated non-linearity,
      particularly above 101.3 kPa (1 bar) PO2, whereas the output of the CO2 sensor
      showed an inverse logarithmic relationship. Cross-sensitivity to helium was
      observed. The mean t90 response times were 90 (SD 10) ms for the O2 sensor, and
      100 (SD 10) ms for the CO2 sensor. Breath-by-breath recordings showed slight
      damping of the CO2 trace due to electronic filtering. Power consumption was 1.5-2
      W per sensor. CONCLUSIONS: The fast response times would allow accurate breath-by
      breath measurement. Even though the O2 sensor has a non-linear response,
      measurement is possible using multi-point calibration. Further design is
      necessary to allow trimix to be used as the diluent. A major disadvantage is the
      high power consumption needed to heat the sensors to high temperatures.

PMID- 21848113
TI  - Preliminary observations on the effect of hypoxic and hyperbaric stress on
      pulmonary gas exchange in breath-hold divers.
AB  - AIM: To evaluate pulmonary alveolar-capillary membrane integrity and
      ventilation/perfusion mismatch after breath-hold diving. METHODS: Pulmonary
      diffusing capacity to carbon monoxide (DLCO) and nitric oxide (DLNO), haemoglobin
      (Hb) and haematocrit (Hct) were measured in six elite divers before and at 2, 10
      and 25 minutes after a maximal breath-hold dive to a depth of 10 metres' sea
      water. RESULTS: Compared to pre-dive, DLCO showed a slight increase at 2 minutes
      in five subjects and a tendency to decrease at 25 minutes (P < 0.001) in all
      subjects. DLNO showed an increase at 10 minutes in three divers and a slight
      decrease at 25 minutes in five subjects. There was a small but significant (P <
      0.001) increase in Hb and Hct at 2 minutes, possibly affecting the DLCO
      measurements. CONCLUSIONS: An early but transient increase in DLCO in five divers
      may reflect the central shift in blood volume during a breath-hold dive. The late
      parallel decrease in DLCO and DLNO likely reflects alveolar-capillary distress
      (interstitial oedema). The DLNO increase in three subjects at 10 minutes may
      suggest ventilation/perfusion mismatch.

PMID- 21848114
TI  - Controversial issues in hyperbaric oxygen therapy: a European Committee for
      Hyperbaric Medicine Workshop.
AB  - Every few years, the European Committee for Hyperbaric Medicine (ECHM) publishes
      its recommendations concerning the clinical indications for hyperbaric oxygen
      therapy (HBOT). The last recommendations were issued during the 7th European
      Consensus Conference on Hyperbaric Medicine in 2004. Since then, several
      publications have reported on the use of HBOT in some indications in which it has
      not yet been recommended routinely, namely aseptic bone necrosis, global brain
      ischaemia and autism. Patients or their families push physicians and staff of
      hyperbaric facilities to use hyperbaric treatment regardless of the quality of
      the scientific evidence. Therefore, the ECHM Workshop "Controversial issues in
      hyperbaric oxygen therapy" was convened as a satellite meeting of the 2010
      European Underwater and Baromedical Society Annual Scientific Meeting in
      Istanbul, Turkey in 2010. For each topic, a set procedure was used: first came a
      general report by specialists in the topic, incorporating a review of current
      pathophysiological, experimental and clinical evidence. Then, there were reports
      from hyperbaric facilities that had gained clinical experience in that condition,
      followed by a general discussion with specialists present in the audience.
      Finally, statements regarding each topic were proposed and voted on by the
      audience and these were presented to the ECHM Executive Board for consideration
      and possible approval. In conclusion, the use of HBOT in femoral head necrosis
      will be proposed during the next ECHM Consensus Conference to become an
      'accepted' indication; whilst the use of HBOT in global brain ischaemia and
      autism should retain its current ECHM recommendations, that it should be
      'optional' and 'non-accepted' respectively.

PMID- 21848116
TI  - The death of buddy diving?

PMID- 21848115
TI  - Hyperbaric oxygen therapy improved both pain scores and range of motion in
      patients with early idiopathic femoral head necrosis (Ficat stage II).

PMID- 21848117
TI  - First detection of pike fry-like rhabdovirus in barbel and spring viraemia of
      carp virus in sturgeon and pike in aquaculture in the Czech Republic.
AB  - Rapid antigen detection enzyme-linked immunosorbent assay (ELISA) testing of cell
      cultures with organ homogenate from fish, collected from farms with a
      predominance of common carp or in natural aquaculture in the Czech Republic
      between 1995 and 2008, identified piscine vesiculovirus in 27 of 178 samples.
      Using reverse transcription semi-nested PCR, targeting a 550 nucleotide region of
      the glycoprotein (G) gene, piscine vesiculovirus was confirmed in 23 of the 27
      organ samples diagnosed by ELISA as infected. PCR products were amplified and
      sequenced from 18 isolates from common carp Cyprinus carpio (family Cyprinidae),
      2 isolates from northern pike Esox lucius (family Esocidae), and 1 isolate each
      from Siberian sturgeon Acipenser baerii (family Acipenseridae), common barbel
      Barbus barbus (family Cyprinidae), and koi carp Cyprinus carpio koi (family
      Cyprinidae). The sequences (based on 401 nucleotides) clustered into 2
      genogroups. The majority of isolates (n = 22), including those from sturgeon and
      pike, grouped with the spring viraemia of carp virus (SVCV) Genogroup I and
      Subgroup Id. The 22 isolates could be further subdivided into 2 groups: Id1 (n =
      20) and Id2 (n = 2). A marker (a non-conservative nucleotide substitution) for
      the Id1 SVCV group was identified. It was specifically found in all sequences of
      Id1 isolates when testing SVCV originating from different countries. The
      remaining isolate from barbel, was classified in the pike fry-like rhabdovirus
      Genogroup IV. This is the first confirmation of natural SVCV infection in
      sturgeon and pike, and pike fry-like rhabdovirus infection in barbel. In the case
      of the pike fry-like rhabdovirus, this is also its first identification in the
      Czech Republic. According to the presence/absence of evident clinical signs of
      rhabdoviral disease in the 3 infected hosts, only the sturgeon seemed to be
      susceptible to the monitored rhabdovirus.

PMID- 21848118
TI  - Development and validation of a reverse transcription quantitative PCR for
      universal detection of viral hemorrhagic septicemia virus.
AB  - Viral hemorrhagic septicemia virus (VHSV) infects over 70 fish species inhabiting
      marine, brackish or freshwater environments throughout the Northern Hemisphere.
      Over its geographic range, 4 VHSV genotypes and multiple subtypes exist. Here, we
      describe the development and validation of a rapid, sensitive and specific real
      time reverse transcription quantitative PCR assay (RT-qPCR) that amplifies
      sequence from representative isolates of all VHSV genotypes (I, II, III and IV).
      The pan-specific VHSV RT-qPCR assay reliably detects 100 copies of VHSV
      nucleoprotein RNA without cross-reacting with infectious hematopoietic necrosis
      virus, spring viremia of carp virus or aquatic birnavirus. Test performance
      characteristics evaluated on experimentally infected Atlantic salmon Salmo salar
      L. revealed a diagnostic sensitivity (DSe) > or = 93% and specificity (DSp) =
      100%. The repeatability and reproducibility of the procedure was exceptionally
      high, with 93% agreement among test results within and between 2 laboratories.
      Furthermore, proficiency testing demonstrated the VHSV RT-qPCR assay to be easily
      transferred to and performed by a total of 9 technicians representing 4
      laboratories in 2 countries. The assay performed equivalent to the traditional
      detection method of virus isolation via cell culture with the advantage of faster
      turnaround times and high throughput capacity, further suggesting the suitability
      of the use of this VHSV RT-qPCR in a diagnostic setting.

PMID- 21848119
TI  - Characterization of photochromogenic Mycobacterium spp. from Chesapeake Bay
      striped bass Morone saxatilis.
AB  - A large diversity of Mycobacterium spp. has been isolated from striped bass
      Morone saxatilis in Chesapeake Bay, USA. The new species M. shottsii and M.
      pseudoshottsii are the dominant isolates, while the classical fish pathogen M.
      marinum is found much less frequently. M. fortuitum and M. chelonae, other
      Mycobacterium spp. known to commonly infect fishes, have not yet been aseptically
      isolated from striped bass within Chesapeake Bay. While M. pseudoshottsii and M.
      shottsii have been phenotypically and genotypically characterized, other less
      common mycobacterial isolates have not. In the present study, we describe 17
      photochromogenic isolates from Chesapeake Bay striped bass using phenotypic
      characterization and multilocus sequencing of 16S rRNA, hsp65 and rpoB genes.
      Genetic characterization reveals that these isolates are related to widely
      divergent portions of the mycobacterial phylogeny; however, some interesting
      trends are observed, such as a majority of isolates (10/17) belonging to the M.
      simiae-related grouping. Five additional isolates were assigned to the slow
      growing mycobacteria (including 2 identified as M. marinum), while 2 are clearly
      shown to belong genetically to the fast-growing mycobacteria.

PMID- 21848120
TI  - Experimentally induced marine flexibacteriosis in Atlantic salmon smolts Salmo
      salar. II. Pathology.
AB  - The fish disease marine flexibacteriosis is characterised by necrotic lesions on
      the body, head, fins, and occasionally gills, with erosive lesions on the
      external surface as the prominent clinical sign. In Australia, the main species
      affected are Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss in
      sea-cage culture in Tasmania. Using a dose-dependent trial to determine
      pathology, 2 forms of the disease were noted in Atlantic salmon. The acute form
      occurs within 2 to 3 d after inoculation at high doses (1 x 10(8) cells ml(-1))
      and is characterised by the disintegration of the epithelium. The chronic form of
      the disease began as small superficial blisters of the epidermis, which develop
      into ulcerative lesions that leave musculature exposed. The predominant lesion
      sites were the dorsum and pectoral fins. Jaws were commonly affected, and gill
      necrosis was also noted. Behaviour of Atlantic salmon as well as the conditions
      under which they were kept contribute to the size and distribution of lesions
      observed. Lack of an inflammatory response in pathology and rapid and destructive
      mortalities observed in higher inoculum doses suggested a role of toxins in the
      pathogenesis of Tenacibaculum maritimum. This is the first study to examine the
      development of marine flexibacteriosis lesions and to utilise
      immunohistochemistry to verify that the bacteria observed in histology was T.
      maritimum.

PMID- 21848121
TI  - Rainbow trout Oncorhynchus mykiss ladderlectin, but not intelectin, binds viral
      hemorrhagic septicemia virus IVb.
AB  - The innate immune system of fish is critical for rapid detection and immediate
      response to infection, as well as to orchestrate the adaptive branch of the
      immune system. Rainbow trout Oncorhynchus mykiss ladderlectin and intelectin are
      plasma pattern recognition receptors (PRR) for bacterial and fungal pathogens of
      rainbow trout, but their role as PRRs for virus is unknown. Viral hemorrhagic
      septicemia virus (VHSV) IVb is a recently described fish pathogen in the Great
      Lakes, and rainbow trout can be experimentally infected. Using an indirect enzyme
      linked immunosorbent assay, rainbow trout plasma ladderlectin significantly (p <
      0.05) bound purified VHSV while intelectin did not. In addition, plasma
      ladderlectin but not intelectin was eluted from a VHSV-conjugated Toyopearl
      column using EDTA. Protein identification was confirmed with polyclonal antiserum
      used with slot immunoblot, 1-dimensional sodium dodecyl sulphate polyacrylamide
      electrophoresis, and Western immunoblot.

PMID- 21848122
TI  - Sphaerothecum destruens pathology in cyprinids.
AB  - Sphaerothecum destruens is a significant intracellular parasite of fish which has
      caused disease and mortalities in cultured north American Chinook salmon
      Oncorhynchus tshawytscha and Atlantic salmon Salmo salar. Several hosts for S.
      destruens have been identified within the Salmonidae family, and the
      histopathology of the infection can differ between hosts. Recently, S. destruens
      has been associated with the most invasive cyprinid species in Europe, topmouth
      gudgeon Pseudorasbora parva. Accurate disease identification based on thorough
      descriptions of clinical signs and histopathology in this new range of hosts is
      thus paramount to support further epizootiological studies. In this study, the
      associated histopathology of S. destruens infection is described along with its
      pathogenesis in the endangered cyprinid sunbleak Leucaspius delineatus.
      Histological examination of 100 L. delineatus in a wild population in the south
      of England revealed the presence of S. destruens infections, with a prevalence of
      5% with S. destruens, suggesting an over-dispersed distribution within the L.
      delineatus sample. Clinical signs of the infection were absent, but histological
      examination revealed the presence of both disseminated and nodular lesions in
      several organs.

PMID- 21848123
TI  - Soft tunic syndrome in the edible ascidian Halocynthia roretzi is caused by a
      kinetoplastid protist.
AB  - An etiological study was conducted to clarify whether the flagellate-like cells
      found in histological preparations of the tunic of diseased Halocynthia roretzi
      (Drasche) were the causative agent of soft tunic syndrome in this ascidian. When
      pieces of softened diseased tunic were incubated overnight in sterile seawater,
      live flagellated cells, which were actively swimming in the seawater, were
      observed in 47 out of 61 diseased ascidians (77%), but not in moribund or
      abnormal individuals with normal tunics (n = 36) nor in healthy animals (n = 19).
      The flagellate was morphologically very similar to those observed in histological
      sections of the diseased tunic. By contrast, flagellates were not found in tunic
      pieces of healthy, moribund, and abnormal individuals that did not exhibit
      softening of the tunic. Light and electron microscopy revealed that the
      flagellate has polykinetoplastic mitochondria with discoidal cristae. The
      cytomorphologies of the flagellate were the same as those of the flagellate-like
      cells in the diseased tunic. We cultured the flagellate from the softened tunic
      in vitro and confirmed that the tunics of healthy ascidians, which were immersion
      challenged with suspensions of the subcultured flagellates, became softened 17 d
      after exposure, including the final 12 d in aerated, running seawater. The
      occurrence of flagellates was also confirmed by incubating pieces of soft tunic
      from experimentally infected animals in seawater overnight. These results
      indicate that the flagellate is the causative agent of soft tunic syndrome.

PMID- 21848124
TI  - Salt gland adenitis as only cause of stranding of loggerhead sea turtles Caretta
      caretta.
AB  - The present study describes pathological and microbiological findings in 9
      stranded loggerhead sea turtles Caretta caretta, whose only observed lesion was
      bilateral purulent salt gland adenitis. Histological lesions ranged from the
      presence of abundant eosinophilic material associated with bacterial colonies in
      the lumen of the central ducts of the glandular lobules to the destruction of the
      glandular tissue and presence of abundant eosinophilic material composed of
      heterophils and cell debris, lined by multinucleated giant cells. Aeromonas
      hydrophila, Staphylococcus sp., and Vibrio alginolyticus were the bacteria most
      frequently isolated. Plasma concentrations of sodium and chloride and plasma
      osmolality from 2 turtles suffering from salt gland adenitis were, respectively
      45.7, 69.2, and 45.7% higher than the mean value for healthy turtles. These cases
      suggest that failure to maintain homeostasis due to severe lesions in the salt
      glands can cause stranding and/or death of loggerhead sea turtles.

PMID- 21848125
TI  - Colonization of turbot tissues by virulent and avirulent Aeromonas salmonicida
      subsp. salmonicida strains during infection.
AB  - Preventing disease outbreaks in cultured turbot Psetta maxima L. caused by
      Aeromonas salmonicida subsp. salmonicida (ASS) requires a better understanding of
      how this pathogen colonizes its host. Distribution of 1 virulent and 2 avirulent
      ASS strains in turbot tissues was investigated during early and late stages of
      infection following an immersion challenge. To track bacteria within the turbot,
      the ASS strains were tagged with green fluorescent protein (GFP). Both virulent
      and avirulent strains colonized the epidermal mucus, gills, and intestine within
      the first 12 h post challenge, suggesting that these sites may serve as points of
      entry into turbot. Although the avirulent strains colonized these initial sites
      in the turbot tissues, they were rarely found in the internal organs and were
      cleared from the host 4 d post challenge. In contrast, the virulent ASS strain
      was found in the liver and kidney as early as 12 h post challenge and was found
      in the muscle tissue at very late stages of infection. The virulent strain
      persisted in all tested host tissues until death occurred 7 d post challenge,
      suggesting that ASS must colonize and survive within the turbot tissues for an
      infection to result in death of the fish. Comparisons of the distribution
      profiles of both virulent and avirulent strains during early and late stages of
      an infection in turbot has provided important information on the route and
      persistence of an ASS infection in this host.

PMID- 21848126
TI  - Luna stain, an improved selective stain for detection of microsporidian spores in
      histologic sections.
AB  - Microsporidia in histologic sections are most often diagnosed by observing spores
      in host tissues. Spores are easy to identify if they occur in large aggregates or
      xenomas when sections are stained with hematoxylin and eosin (H&E). However,
      individual spores are not frequently detected in host tissues with conventional
      H&E staining, particularly if spores are scattered within the tissues, areas of
      inflammation, or small spores in nuclei (i.e. Nucleospora salmonis). Hence, a
      variety of selective stains that enhance visualization of spores is recommended.
      We discovered that the Luna stain, used to highlight eosinophils, red blood
      cells, and chitin in arthropods and other invertebrates, also stains spores of
      Pseudoloma neurophilia. We compared this stain to the Gram, Fite's acid fast,
      Giemsa, and H&E stains on 8 aquatic microsporidian organisms that were readily
      available in our 2 laboratories: Loma salmonae, Glugea anomala, Pseudoloma
      neurophilia, Pleistophora hyphessobryconis, Pleistophora vermiformis, Glugea sp.,
      Steinhausia mytilovum, and an unidentified microsporidian from UK mitten crabs
      Eriocheir sinensis. Based on tinctorial properties and background staining, the
      Luna stain performed better for detection of 6 of the 8 microsporidia. Gram stain
      was superior for the 2 microsporidia from invertebrates: S. mytilovum and the
      unidentified microsporidian from E. sinensis.

PMID- 21848127
TI  - Breast cancer incidence and neighbourhood income.
AB  - BACKGROUND: In developed countries, women of higher socioeconomic status often
      have higher breast cancer incidence rates, compared with women of lower
      socioeconomic status. DATA AND METHODS: Data were extracted from the Canadian
      Cancer Registry for the 229,955 cases of adult female invasive breast cancer
      diagnosed from 1992 through 2004. Postal code at diagnosis was used to determine
      neighbourhood income quintile. Breast cancer incidence was examined by year,
      region, age and neighbourhood income quintile. Census data for 1991 on children
      ever born and British Columbia data for 2006 on first-time attendance at
      mammography screening were analyzed by neighbourhood income quintile. RESULTS:
      Residence in the lowest as opposed to the highest neighbourhood income quintile
      was associated with a 15% lower risk of being diagnosed with breast cancer.
      Higher income levels were associated with lower parity in 1991 and a higher
      prevalence of first-time screening mammography in British Columbia in 2006.
      INTERPRETATION: Canadian data support an association between the diagnosis of
      invasive breast cancer and neighbourhood income quintile. Parity and mammography
      screening may account for some differences in incidence.

PMID- 21848128
TI  - Associations between household food insecurity and health outcomes in the
      Aboriginal population (excluding reserves).
AB  - BACKGROUND: Aboriginal people are more vulnerable to food insecurity and
      morbidity than is the Canadian population overall. However, little information is
      available about the association between food insecurity and health in Aboriginal
      households. DATA AND METHODS: Data from the 2004 Canadian Community Health Survey
      Nutrition were used to examine the relationships between household food security
      and self-reported health, well-being and health behaviours in a sample of 837
      Aboriginal adults living off reserve. Household food security status was based on
      Health Canada's interpretation of the United States Household Food Security
      Survey Module. Multivariable logistic regression was used to identify significant
      relationships, while adjusting for potential confounders. RESULTS: An estimated
      29% of Aboriginal people aged 18 or older lived in food-insecure households. They
      were more likely to report poor general and mental health, life dissatisfaction,
      a very weak sense of community belonging, high stress and cigarette smoking,
      compared with their counterparts in food-secure households. When age, gender and
      household education were taken into account, respondents from food-insecure
      households had significantly higher odds of poor general health, high stress,
      life dissatisfaction, and a very weak community belonging. INTERPRETATION:
      Reductions in household food insecurity may improve the health and well-being of
      Aboriginals living off-reserve.

PMID- 21848129
TI  - Conditional survival analyses across cancer sites.
AB  - Survival estimates measured from the time cancer diagnosis become less
      informative after one or two years' survival. Using records from the Canadian
      Cancer Registry linked to the Canadian Vital Statistics Death Database, five-year
      conditional relative survival ratio (RSR) estimates were derived for a large
      number of cancers. For each cancer with an initial five-year RSR of at least 80%
      (except breast cancer), a conditional five-year RSR of 95% or more was achieved
      after five years' survival. Among cancers with initial five-year RSRs of 50% to
      79%, a five-year conditional RSR of 95% or more was observed for cancers of the
      cervix uteri and colon after five years. There was no apparent improvement in
      survival prospects during the first five years after diagnosis for chronic
      lymphocytic leukemia (CLL). Despite initial prognoses of less than 50%, a
      conditional five-year RSR of at least 90% five years after diagnosis was achieved
      for stomach cancer and leukemia (excluding CLL).

PMID- 21848130
TI  - Cognitive performance of Canadian seniors.
AB  - With data from the 2009 Canadian Community Health Survey--Healthy Aging Cognition
      Module, five cognitive functioning categories based on normative values that
      adjust for age, sex and education were created. The two lowest categories were
      combined to identify seniors (65 or older) without Alzheimer's disease or
      dementia living in private households, who had low scores on four cognitive
      tasks: first recall, second recall, semantic fluency, and processing speed. Low
      income, not living with a spouse or partner, and diabetes were associated with
      low scores on each task. Heart disease, impairment in instrumental and daily
      activities, receiving home care, social participation, loneliness, and self
      perceived general and mental health were also associated with low cognitive
      performance, although the associations differed by cognitive task.

PMID- 21848131
TI  - Psychometric properties, factorial structure, and measurement invariance of the
      English and French versions of the Medical Outcomes Study social support scale.
AB  - BACKGROUND: The Medical Outcomes Study (MOS) social support scale is a 19-item
      survey that measures four dimensions of functional support. The current study
      reports on the psychometric properties, factorial structure, and measurement
      invariance of the scale for a sample of English- and French-speaking Canadians
      aged 55 or older. DATA AND METHODS: The internal consistency and composite
      reliability for a congeneric measurement model of the dimensions of functional
      social support were examined. A confirmatory factor analysis and test of
      invariance across language (English = 2,642; French = 489) were also performed.
      RESULTS: Across both English- and French-speaking respondents, results indicated
      good internal consistency (Cronbach's alpha ranged from .90 to .97) and composite
      reliability (ranging from .93 to .97) for all dimensions of functional social
      support. The confirmatory factor analysis revealed acceptable fit indices for the
      4-factor structure similar to the original one. The scale appears to function
      uniformly across both language groups. INTERPRETATION: The MOS social support
      scale appears to be a psychometrically sound instrument for use in research on
      social support with samples of English- and French-speaking older adults.

PMID- 21848132
TI  - Primary mental health care visits in self-reported data versus provincial
      administrative records.
AB  - BACKGROUND: Survey data and provincial administrative health data are the major
      sources of population estimates of mental health care visits to General
      Practitioners (GPs). Previous research has suggested that self-reported estimates
      of the number of mental health-related visits per person to health professionals
      may exceed estimates obtained from physician reimbursement records. DATA AND
      METHODS: Self-reported data from the 2002 Canadian Community Health Survey
      (CCHS): Mental Health and Well-being and administrative records from the Medical
      Services Plan of British Columbia were linked. The analytic sample consisted of
      145 CCHS respondents who had at least one mental health visit to a GP in the past
      12 months according to both data sources. High Reporters (self-reported visits
      exceeded number in administrative data), Low Reporters (self-reported visits were
      less than number in administrative data), and Exact Matches were analyzed in two
      ways. The first analysis used diagnostic codes to identify mental health-related
      visits in the administrative data. For the second analysis, all GP visits in the
      administrative data were counted as "possibly" mental health-related. Differences
      were described based on the median number of visits. RESULTS: When diagnostic
      codes were used to identify mental-health-related visitis in the administrative
      data, High Reporters (49%) substantially exceeded Low Reporters (24%). The
      remaining 27% were Exact Matches. Based on a broader definition of a mental
      health visit, 51% were Exact Matches. High reporting was common among people with
      mental disorders. INTERPRETATION: Self-reported data and administrative data
      provide different estimates of the number of mental health visits per person to
      GPs. The discrepancy can be large.

PMID- 21848133
TI  - Global urban growth and the geography of water availability, quality, and
      delivery.
AB  - Globally, urban growth will add 1.5 billion people to cities by 2030, making the
      difficult task of urban water provisions even more challenging. In this article,
      we develop a conceptual framework of urban water provision as composed of three
      axes: water availability, water quality, and water delivery. For each axis, we
      calculate quantitative proxy measures for all cities with more than 50,000
      residents, and then briefly discuss the strategies cities are using in response
      if they are deficient on one of the axes. We show that 523 million people are in
      cities where water availability may be an issue, 890 million people are in cities
      where water quality may be an issue, and 1.3 billion people are in cities where
      water delivery may be an issue. Tapping into groundwater is a widespread
      response, regardless of the management challenge, with many cities unsustainably
      using this resource. The strategies used by cities deficient on the water
      delivery axis are different than for cities deficient on the water quantity or
      water quality axis, as lack of financial resources pushes cities toward a
      different and potentially less effective set of strategies.

PMID- 21848134
TI  - Climate warming and pikeperch year-class catches in the Baltic Sea.
AB  - Climate change scenarios concerning the Baltic Sea predict increase in surface
      water temperatures. Pikeperch (Sander lucioperca (L.)) inhabits the coastal areas
      of the northern Baltic Sea and is an important fish species for the Finnish
      fisheries. The year-class strength of pikeperch varies strongly between years and
      significantly depends on water temperature. We aimed to study the effects of
      changing temperature conditions on pikeperch fisheries and distribution based on
      commercial catch data from the period 1980-2008 in the Finnish coastal areas of
      the Baltic Sea. The results indicated that warmer summers will produce stronger
      pikeperch year-classes that consequently contribute significantly to the future
      catches. The average temperature in June-July explained 40% of the variation in
      the year-class catches in the Gulf of Finland and 73% in July-August in the
      Archipelago Sea. During the study period, the distribution of pikeperch catches
      expanded toward north along the coasts of the Bothnian Sea.

PMID- 21848135
TI  - Assessing the impacts of establishing MPAs on fishermen and fish merchants: the
      case of Lyme Bay, UK.
AB  - Shortly after the implementation of a marine protected area (MPA) in Lyme Bay in
      2008, inside which scallop dredging and bottom trawling is prohibited, a socio
      economic impact assessment was initiated. This article presents the initial
      findings from this study. The aim was to understand the costs and benefits to
      fishermen and fish merchants of establishing the MPA. These were assessed using a
      combination of primary and secondary data. The results indicate that the impacts
      of the closure differ according to the gear type and the fishing location used by
      the fishermen. Static gear fishermen who fish inside the closed area have seen
      changes in terms of increased fishing effort, mostly because they have been able
      to increase the number of crab and whelk pots they deploy. The effects of the
      closure on static gear fishermen who fish outside the closed area has been
      reported in terms of increased conflicts with towed gear fishermen who now fish
      regularly in their traditional grounds. Fishermen using towed gear on the other
      hand have been impacted through displacement effects as they have been forced to
      look for other fishing grounds outside the closed area. Most fish merchants and
      processors initially claimed that they were heavily impacted by the closure but
      when they were interviewed 1 year after the closure they suggested a more stable
      picture. Preliminary analyses of landings data indicate that the introduction of
      the MPA has so far had minimal impacts on the average incomes and financial
      profits of fishermen and fish merchants. This conclusion, however, reflects a
      short-term view as the impacts of the closure of Lyme Bay are likely to be felt
      for a long time to come.

PMID- 21848136
TI  - Management implications of the response of two tilapiine cichlids to long-term
      changes in lake level, allodiversity and exploitation in an equatorial lake.
AB  - The tilapiine cichlids Oreochromis leucostictus and Tilapia zillii were
      introduced into Lake Naivasha, Kenya, in 1956. Previous studies on data collected
      to 1987 revealed they were persistent following establishment, despite
      environmental variability and exploitation. Recent data, however, suggest this
      persistence is under threat as data indicate some significant declines in aspects
      of their abundance since 1999. The influence of changes in lake level,
      allodiversity and fishing effort on this decline was tested and showed that a
      decline in lake level was a significant causal factor. The recent change in
      allodiversity, with the establishment and dominance of Cyprinus carpio in the
      fishery, was not significant on the catch per unit effort of O. leucostictus but
      was on T. zillii. Since 1999, catches of tilapiines in the fishery have been
      independent of fishing effort, contrary to between 1975 and 1987, suggesting
      their management through application of fishery models may no longer be
      applicable. As it was anthropogenic-mediated lake level changes that were mainly
      responsible for their decline, then lake management should focus on sustainable
      water utilization that maximizes lake levels in accordance with the basin-wide
      water balance.

PMID- 21848137
TI  - Is biodiversity friendly fisheries management possible on Issyk-Kul Lake in the
      Kyrgyz Republic?
AB  - This paper aims to identify challenges, and threats, and further explore
      opportunities for a new Biodiversity Friendly Fisheries Management Regime on the
      Issyk-Kul Lake in the Kyrgyz Republic. This lake is the second largest high
      altitude lake in the world providing recreational and small-scale fishing
      activities as well as cage culture of introduced species. The populations of
      several indigenous species are seriously threatened, because many of the
      introduced species are potential predators. We examine the root causes for
      overfishing and relationships of alien and endemic fish species in Issyk-Kul Lake
      and give possible policy options that can help remediate or mitigate the
      biodiversity degradation. This analysis focuses on necessary legal modifications,
      institutional cooperation, the protection of selected endemic fish species,
      control of the alien species, the sustainable extension services and management
      of fish ponds. Fisheries co-management is one option to explore shared
      stewardship and empowering user groups on the lake. A comprehensive fisheries
      management plan is also needed, in addition to immediate action and further
      studies on the following wider aspects: water management/irrigation issues, water
      quality assessment near cage cultures, sociocultural issues, resource inventory,
      and assessing fish biology and the lake ecosystem.

PMID- 21848138
TI  - Unusual salinity conditions in the Yangtze estuary in 2006: impacts of an extreme
      drought or of the Three Gorges Dam?
AB  - During the extreme dry year of 2006, abnormal salinity conditions in the
      Changjiang Estuary of the Yangtze River occurred in partial coincidence with the
      second impoundment phase of the TGD (Three Gorges Dam). Analysis of discharge
      observations in the upper reaches of the estuary and of salinity observations in
      the estuary as a whole reveals that in 2006 salinity was over 100 mg/l during 275
      days, over 250 mg/l during 75 days and over 400 mg/l during 48 days. It is well
      known that this is due to extreme low discharges from the upper catchment area
      into the estuary. Moreover, large amounts of water consumed along the lower
      reaches of the Yangtze River can also aggravate the low discharges that lead to
      stronger saltwater intrusion in the estuary. Of the 75 days that salinity was
      over 250 mg/l, the low discharge was decreased further by 10 to 20% due to water
      consumption. The additional impact of the impoundment phase of the TGD (lasting
      37 days in autumn) was noticeable only during 7 days in 2006. During that period,
      the relative contributions of the TGD and the water consumption in the lower
      reaches of the Yangtze River amounted to 70 and 30%, respectively. It may be
      concluded that the impact of the second impoundment phase of the TGD on salinity
      intrusion in the estuary was modest, while the extreme drought of 2006 was the
      dominant cause.

PMID- 21848139
TI  - Projecting climate change effects on forest net primary productivity in
      subtropical Louisiana, USA.
AB  - This study projected responses of forest net primary productivity (NPP) to three
      climate change scenarios at a resolution of 5 km x 5 km across the state of
      Louisiana, USA. In addition, we assessed uncertainties associated with the NPP
      projection at the grid and state levels. Climate data of the scenarios were
      derived from Community Climate System Model outputs. Changes in annual NPP
      between 2000 and 2050 were projected with the forest ecosystem model PnET-II.
      Results showed that forest productivity would increase under climate change
      scenarios A1B and A2, but with scenario B1, it would peak during 2011-2020 and
      then decline. The projected average NPP under B1 over the years from 2000 to 2050
      was significantly different from those under A1B and A2. Forest NPP appeared to
      be primarily a function of temperature, not precipitation. Uncertainties of the
      NPP projection were due to large spatial resolution of the climate variables.
      Overall, this study suggested that in order to project effects of climate change
      on forest ecosystem at regional level, modeling uncertainties could be reduced by
      increasing the spatial resolution of the climate projections.

PMID- 21848140
TI  - Can repeated fertilizer applications to young Norway spruce enhance avian
      diversity in intensively managed forests?
AB  - Repeated fertilization of forests to increase biomass production is an
      environmentally controversial proposal, the effects of which we assessed on
      breeding birds in stands of young Norway spruce (Picea abies), in an intensively
      managed forest area in southern Sweden. Our results show that fertilized stands
      had 38% more species and 21% more individuals than unfertilized stands. Compared
      with stands under traditional management, the further intensification of forestry
      by repeated applications of fertilizers thus seemed to enhance species richness
      and abundance of forest birds. We cannot conclude at this stage whether the
      response in the bird community was caused by changes in food resources or
      increased structural complexity in the forest canopy due to the skid roads used
      for the application of the fertilizers. Future studies should focus on structural
      and compositional effects of fertilization processes during the entire rotation
      period and at assessing its effects in a landscape

PMID- 21848141
TI  - Impacts of surface gold mining on land use systems in Western Ghana.
AB  - Land use conflicts are becoming increasingly apparent from local to global
      scales. Surface gold mining is an extreme source of such a conflict, but mining
      impacts on local livelihoods often remain unclear. Our goal here was to assess
      land cover change due to gold surface mining in Western Ghana, one of the world's
      leading gold mining regions, and to study how these changes affected land use
      systems. We used Landsat satellite images from 1986-2002 to map land cover change
      and field interviews with farmers to understand the livelihood implications of
      mining-related land cover change. Our results showed that surface mining resulted
      in deforestation (58%), a substantial loss of farmland (45%) within mining
      concessions, and widespread spill-over effects as relocated farmers expand
      farmland into forests. This points to rapidly eroding livelihood foundations,
      suggesting that the environmental and social costs of Ghana's gold boom may be
      much higher than previously thought.

PMID- 21848142
TI  - Soaring extinction threats to endemic plants in Brazilian metal-rich regions.

PMID- 21848143
TI  - The potential of bamboo is constrained by outmoded policy frames.

PMID- 21848145
TI  - All patients deserve our respect.

PMID- 21848144
TI  - Societal learning needed to face the water challenge.

PMID- 21848146
TI  - King's Fund urges NHS to adopt shared leadership style that involves care staff.

PMID- 21848147
TI  - Southern Cross launches new care strategy.

PMID- 21848148
TI  - Diversity in action.

PMID- 21848149
TI  - Safe staffing raises issues.

PMID- 21848150
TI  - Doing the right thing.

PMID- 21848151
TI  - T is for theory.

PMID- 21848152
TI  - Forum to help staff deal with day-to-day stress.
AB  - Schwartz Center rounds were piloted by the King's Fund in 2009 and other hospital
      trusts have now taken up the concept. The rounds provide a forum for staff to
      discuss social and emotional issues surrounding patient care, and lead to changes
      in the workplace.

PMID- 21848153
TI  - Treating older people with dignity and respect.
AB  - A report into services for older people in Wales highlights shortcomings that can
      be improved by learning from examples of good practice, improving staff training
      and better workforce planning.

PMID- 21848154
TI  - Nurses' role in liaising between patients and service providers.
AB  - Patient and public involvement (PPI) has become part of the UK's health and
      social care system and is promoted as a necessary component of a modern NHS that
      is responsive to users and works in partnership with the communities it serves.
      Its implementation, however, poses challenges for staff working in pressured
      settings, such as emergency departments. This article outlines the history of PPI
      and the role of nurses in ensuring the policy is championed at the front line of
      care.

PMID- 21848155
TI  - Tool to assess the cost and quality benefits of nursing innovation.
AB  - Understanding the economic value of nursing services in a time of unprecedented
      public sector cuts is a challenge. The economic assessment tool (EAT) (RCN 2011)
      has been designed by the authors of the article for this purpose and generates
      return on investment dividends for nursing innovations and services. The EAT,
      which is built on the discipline of improvement and uses many of its tools and
      techniques, involves four stages: mapping, costing, calculating and reporting.
      The nursing profession systematically captures a range of clinical data as part
      of routine care to which monetary values can be assigned. The EAT exploits these
      data and provides the profession with the economic evidence it might need to
      sustain quality nursing services in financially uncertain times.

PMID- 21848156
TI  - Initiative to change ward culture results in better patient care.
AB  - One of the main features of ward rounds is the professional conversation that
      occurs between doctors and nurses. Such conversation needs to be perfected to
      avoid iatrogenic harm and increase efficiency. This article looks at data
      collected from 146 consultant-led medical ward rounds at a hospital trust using
      the Caldwell considerative checklist process (Herring et al 2011) to identify the
      frequency and quality of such conversations. A total of 1,921 patients' reviews
      were undertaken. A nurse was present during preparatory discussions on 604
      occasions (31 per cent) and during bedside review on 1,134 occasions (59 per
      cent). These data demonstrate an urgent need to change ward cultures to improve
      the professional conversations between doctors, nurses and patients. By
      increasing nurse presence as a result of this research patient care and safety
      has improved at ward level, increasing satisfaction for everyone involved.

PMID- 21848157
TI  - A service second to none.

PMID- 21848158
TI  - ACOs and Medicare ... quo vadis?

PMID- 21848159
TI  - Preparation is key to ICD-10 success.

PMID- 21848160
TI  - MGMA outlines medical group concerns with proposed ACO rule.

PMID- 21848161
TI  - Survival basics for an ever-changing EHR marketplace.

PMID- 21848162
TI  - 7 tips for meaningful EHR use.

PMID- 21848163
TI  - Member restructures practice with BOK, saves thousands of dollars.

PMID- 21848164
TI  - Thrive in the new healthcare market. Retool your skill set to retain your edge.

PMID- 21848165
TI  - Improving patient health drives PCMH interest.

PMID- 21848167
TI  - Are you a team player?

PMID- 21848166
TI  - Operations issues and quality indicators dominate practice challenges in 2011.

PMID- 21848168
TI  - The story behind the numbers. What issues are most applicable to your practice?

PMID- 21848169
TI  - Finding balance.

PMID- 21848170
TI  - Prepare to be influenced.

PMID- 21848171
TI  - 2011 John H. Gibbon, Jr. Award Lecture. Be prepared. Be safe. Feel safe.

PMID- 21848172
TI  - Clinical evaluation of the accuracy and precision of the CDI 500 in-line blood
      gas monitor with and without gas calibration.
AB  - During cardiopulmonary bypass blood gases can be analyzed with laboratory
      equipment or with an in-line monitor giving instant results. The manufacturer of
      the CDI 500 in-line blood gas monitor recommends gas calibration before use. In
      acute cases there may not be time to perform a gas calibration. We hypothesized
      that after calibration against laboratory results, the CDI values of pH, pO2, and
      pCO2 will keep the same level of accuracy, whether the CDI has been gas
      calibrated or not. We performed a prospective randomized observational study
      using a study group without gas calibration (29 patients) and a control group
      with gas calibration (29 patients). Blood sampling was done at the beginning of
      bypass, and 30 minutes later. After each blood sample the CDI was in-vivo
      calibrated to the values simultaneously obtained from the ABL. Before in-vivo
      calibration values from the CDI without gas calibration were significantly
      different from the ABL-values in accuracy as well as precision, whereas the
      results from the gas calibrated CDI were largely consistent with the ABL. Before
      in-vivo calibration, the CDI without gas calibration was completely unreliable.
      After in-vivo calibration there was no statistical difference between the values
      of the CDI with and without calibration. We recommend gas calibration of the CDI
      before use in the period before in-vivo calibration.

PMID- 21848173
TI  - Variation in arterial inflow temperature: a regional quality improvement project.
AB  - Peer-reviewed evidence (Class IIa, Level B) suggests that arterial blood
      temperature should be limited to 37 degrees C during cardiopulmonary bypass. We
      implemented a regional quality improvement initiative to reduce regional
      variability in our performance around this recommendation at four northern New
      England medical centers between January 2006 and June 2010. Cardiovascular
      perfusionists at four medical centers collaborated by conference calls regarding
      blood temperature management. Evidence from the recommendations were reviewed at
      each center, and strategies to prevent hyperthermia and to improve performance on
      this quality measure were discussed. Centers submitted data concerning highest
      arterial blood temperatures among all isolated coronary artery bypass grafting
      procedures between 2006 through June 2010. Scope and focus of local practice
      changes were at the discretion of each center. The timing of each center's
      quality improvement initiatives was recorded, and adherence to thresholds of 37
      degrees C and 37.5 degrees C were analyzed. Data were collected prospectively
      through our regional perfusion registry. Data were available for 4909 procedures
      (1645 before interventions, 3264 after interventions). Prior to the quality
      improvement interventions, 90% of procedures had elevated arterial line
      temperatures (37 degrees C or more), and afterwards it was 69% (p < .001) for an
      absolute difference of 21%. Prior to the intervention, 53% of procedures had
      temperatures beyond a threshold of 37.5 degrees C versus 19% subsequent to
      interventions, for an absolute difference of 34% (p < .001). This regional effort
      to reduce patient exposure to elevated arterial line temperatures resulted in a
      significant sustained reduction in high arterial outflow temperatures at three of
      the four centers. A regional registry provides a means for assessing performance
      against evidence-based recommendations, and evaluating short and long-term
      success of quality improvement initiatives.

PMID- 21848174
TI  - Severe thrombotic and bleeding complications in a baby with heterozygous factor V
      Leiden and acquired von Willebrand disease on ECMO.
AB  - We aim to present the case of a 5-week-old girl with severe respiratory failure
      placed on veno-venous extracorporeal membrane oxygenation (ECMO) that was then
      switched to veno-arterial ECMO. She required up to 60 units/kg/hr of heparin to
      keep her heparin level within the target range at .3-.7 units/mL. During the ECMO
      course, substantial thrombus formation was observed within the venous site of the
      ECMO cannula, which led to two circuit changes on ECMO day 9 and day 20. On ECMO
      day 15, she was noticed to have purpuric lesions on her chest and her right hand
      with no obvious arterial or venous clot detected by Doppler ultrasound. She was
      also noted to have remarkable hemolysis as the plasma free hemoglobin levels were
      substantially elevated up to 700 mg/dL. She was noted to have continuous oozing
      from the catheter insertion sites despite adequate underlying coagulation status.
      Her subsequent platelet function analysis, the thromboelastography, and
      thromboelastography platelet mapping suggested substantial platelet dysfunction.
      Her von Willebrand panel revealed absence of high molecular weight multimers.
      Further coagulation workup was prompted which revealed heterozygosity for factor
      V Leiden. The patient developed severe pulmonary hemorrhages and ECMO was
      discontinued on day 40.

PMID- 21848175
TI  - Successful use of venovenous extracorporeal membrane oxygenation for complicated
      H1N1 pneumonia refractory to mechanical ventilation.
AB  - In April 2009, novel H1N1 influenza A pneumonia was initially identified in young
      adults by the Mexican Health Ministry. Previously healthy patients progressing to
      multisystem organ failure were common. Worldwide, hospitals reported surges in
      intensive care admissions during the initial phase of the pandemic. In patients
      with H1N1 pneumonia refractory to mechanical ventilation, centers were initially
      reporting low survival rates despite the use of extracorporeal membrane
      oxygenation (ECMO). The initial poor outcomes and protracted ECMO treatment
      epochs resulted in centers limiting or withholding the use of ECMO in this
      population. With respect to children with H1N1 infection there was uncertainty
      concerning optimal incorporation of ECMO as a therapeutic option. In children
      with rapidly progressive pneumonia and hypoxia refractory to mechanical
      ventilation, venovenous (VV) ECMO has been successfully used with survival
      ranging from 40-60% depending on the etiology. We report the successful use of VV
      ECMO in two children with confirmed novel H1N1 complicated by bacterial pneumonia
      or morbid obesity. Our Institutional Review Board waived the need for consent.
      Prompt initiation of VV ECMO resulted in rapid clinical improvement, radiographic
      resolution of diffuse consolidation, and return of full neurocognitive function.
      For children with rapidly progressive respiratory distress on conventional
      ventilation, VV ECMO can be used to improve outcomes when initiated early in the
      disease process even in children with a significant co-morbidity.

PMID- 21848176
TI  - Adult respiratory distress syndrome caused by 2009 H1N1 influenza during
      pregnancy: success of ECMO for both the mother and the child.
AB  - Extracorporeal membrane oxygenation (ECMO) is a technique that provides support
      to selected patients with severe respiratory failure. During the 2009 H1N1
      influenza infection outbreak, ECMO was used with a good impact on survival for
      pregnant women, who are at higher risk of H1N1 influenza infection. However,
      there is little information about the survival of fetus post-ECMO therapy in the
      literature. We present a case report of a pregnant patient with severe adult
      respiratory distress syndrome secondary to 2009 H1N1 influenza treated with ECMO.
      The outcome was good both for the mother and her fetus. At 1-year follow-up, her
      child had no neurological or clinical abnormalities. We conclude that ECMO can be
      used safely during pregnancy with a good neurological and clinical outcome for
      the fetus.

PMID- 21848177
TI  - Massive air embolism in a Fontan patient.
AB  - Most institutions performing cardiopulmonary bypass for congenital heart disease
      patients use an integrated hard shell cardiotomy and venous reservoir attached to
      an oxygenator. It is of paramount importance that the integrated reservoir be
      vented so as not to cause pressurization. A pressurized sealed cardiotomy has
      been reported to occur secondary to issues with vacuum assisted venous drainage
      systems as well as improper venting in general. We report a case of air embolus
      caused by retrograde propulsion of air through the venous line secondary to a
      pressurized cardiotomy reservoir in a patient with Fontan circulation. The
      mechanism of cardiotomy pressurization is described, and the scenario simulated
      in a mock circuit.

PMID- 21848178
TI  - Venoarterial air embolism in a Fontan patient by Matte et al.

PMID- 21848179
TI  - Massive systemic air embolism during extracorporeal membrane oxygenation support
      of a neonate with acute respiratory distress syndrome after cardiac surgery.
AB  - Extracorporeal membrane oxygenation (ECMO) is universally accepted as a potential
      lifesaving therapy for neonates suffering severe cardiorespiratory failure, with
      survival reported as 81% weaning off ECMO and 69% to hospital discharge in this
      population. Although ECMO may reduce mortality in certain neonatal patients, it
      is associated with significant complications. Air in the circuit complicates 4.9%
      of neonatal ECMO runs, and it is crucial that all ECMO caregivers are trained in
      the prevention of air embolism and possess the knowledge necessary to efficiently
      identify and remove air from the ECMO circuit to prevent life threatening
      consequences. We present a fatal case of neonatal systemic air embolism leading
      to massive entrainment of air into the ECMO venous return cannula of a neonatal
      patient with acute respiratory distress syndrome following repair of obstructed
      total anomalous pulmonary venous connection. We describe the pathophysiology and
      presentation of this rare condition and the importance of early recognition, due
      to its high mortality rate.

PMID- 21848180
TI  - A technique for autologous priming of the veno-venous bypass circuit during liver
      transplantation.
AB  - Orthotopic liver transplantations (OLT) have been associated with significant
      blood loss and hemodilution, necessitating significant homologous blood component
      replacement. Increasing administration of homologous blood products has been
      found to be inversely related to patient and graft survival. Various methods to
      reduce the amount of blood products patients receive during OLT, such as
      antifibrinolytic therapy, thromboelastography-guided transfusion, phlebotomy,
      reduced central venous pressures intraoperatively, and the use of the veno-venous
      bypass (VVB) circuit, have been explored.The asanguineous priming volume of the
      VVB circuit increases the likelihood of the patient receiving homologous blood
      products due to hemodilution. It was reasoned that autologous priming of the VVB
      circuit in OLT surgery was a plausible adjunctive blood conservation technique
      given its application to the extracorporeal circuit during cardiac surgery. We
      describe our technique of modifying the VVB circuit for autologous priming. This
      technique adds minimal risk and a small amount of cost to the procedure, requires
      slightly more communication among members of the surgical team, and with proper
      sequencing, adds no additional length to the surgical procedure. It is
      recommended that this technique be considered for addition to the arsenal of
      blood conservation techniques when VVB is used during OLT.

PMID- 21848181
TI  - [When technology goes astray].

PMID- 21848182
TI  - [Shortage of organ donors. My heart can be yours].

PMID- 21848183
TI  - [Waterpipe smoking--new, dangerous trend].

PMID- 21848184
TI  - [Waterpipe smoking can cause severe carbon monoxide poisoning. Risk of permanent
      neurologic injuries].

PMID- 21848185
TI  - [Children up to the age of 12 at risk in the traffic. Analysis of traffic
      accidents at the Norrland University Hospital in Umea].

PMID- 21848186
TI  - [Carath--a quality registry and process support. Good possibility for thoracic
      surgery to follow the care process].

PMID- 21848187
TI  - [Evaluation as a tool for quality development of the new residency training. A
      pilot project with two scientific courses at Karolinska University Hospital].

PMID- 21848188
TI  - [Low dosage acetylsalicylic acid plus naproxen--a small risk of interaction].

PMID- 21848189
TI  - [Set up a shadow investigation!].

PMID- 21848190
TI  - ["Screening for abdominal aortic aneurysm in 65-year old men lacks scientific
      evidence].

PMID- 21848191
TI  - [The most vulnerable addicts are forgotten].

PMID- 21848192
TI  - [Right or wrong not to prescribe antibiotics prophylactically?].

PMID- 21848193
TI  - Florida's MCO Medicaid path may be taken by other states.

PMID- 21848194
TI  - How much return does that PhD provide?

PMID- 21848195
TI  - What can be done to counteract growing power of providers? Three health plans
      outline steps they are taking to deal with the effects of growing consolidation
      of providers.

PMID- 21848196
TI  - A new individual market on the horizon. Interview by John Marcille.

PMID- 21848197
TI  - Accountable care--but the patient isn't accountable.

PMID- 21848198
TI  - Will that defibrillator really do the job? A recent report that 1 in 5 implanted
      defibrillators may not be needed raises questions about the medical evidence.

PMID- 21848199
TI  - Giving members a say in benefit plan design. Group Health Cooperative and
      Geisinger Health Plan are two insurers that want members to weigh in on coverage
      issues.

PMID- 21848200
TI  - Adherence to statin therapy saves $944 over 18 months.

PMID- 21848201
TI  - Humana steps back to seize the future. With the purchase of Concentra, a company
      that operates 300 clinics, the health insurer once again provides care.

PMID- 21848202
TI  - Fewer recurrent infections of C. difficile seen with fidaxomicin. This new class
      of antibiotic--the macrocycles--has a greater sustained response against re
      infection than vancomycin.

PMID- 21848203
TI  - ACA's effect on employer-sponsored insurance.

PMID- 21848204
TI  - [Factors to be considered in decision making for quarantine detention with
      emergence of a novel influenza virus].
AB  - OBJECTIVES: In the early phase of the emergence of influenza A (H1N1) 2009
      abroad, quarantine detention measures based on exposure assessment of infected
      persons at airports were enacted in Japan. Detention, while being a step needed
      to protect safety and health of citizens, restricts healthy individuals'
      activities for several days until they can be confirmed to be not infected. Thus,
      the number of persons detained must be minimized in the interest of human rights.
      In this study, we reviewed factors to be considered in decision-making to carry
      out optimal detention in the early phase of emergence of a novel influenza virus
      in the future. METHODS: We reviewed manuscripts on contagiousness of influenza,
      cases of infections in public transportation such as airplanes, and the
      effectiveness of detention, and interviewed persons who were involved in
      detentions in the early phase of the influenza A(H1N1) 2009 pandemic. RESULTS:
      When a decision is made about detention, it is essential to assess the necessity
      of detention, the measures for minimizing the scope of individuals to be
      detained, the measures for ensuring the human rights of individuals affected, and
      possible means to substitute for detention. Assessment of the necessity of
      detention should cover the following: (1) whether or not the novel influenza is a
      sufficiently severe threat to public health to justify detention; (2) whether or
      not detention at a given point of time can delay the beginning of a domestic
      epidemic; and (3) who is responsible and how revision of the once decided
      detentions should be made. Regarding measures for minimizing the scope of
      individuals to be detained, discussions are needed as to: (1) giving advice to
      the nation to refrain from getting aboard an airplane when aware of flu-like
      symptoms so that exposure of people to infected individuals may be avoided; and
      (2) whether or not selection of individuals to be detained is going to be made,
      taking into account the level of exposure to infected individuals. To ensure the
      human rights of the individuals affected by detention, assessment is needed as
      to: (1) whether or not the detention period is as short as possible; (2) whether
      or not human rights (privacy, comfort at the detention facility) will be
      protected during detention; (3) whether or not adequate measures can be taken to
      ensure mental health and management of chronic disease of the detained; and (4)
      whether or not adequate explanations can be given to foreigners to be detained,
      with their mother language taken into account. Regarding substitutes for
      detention, alternatives such as keeping the individuals at their own home as home
      quarantine should be considered. CONCLUSION: The decision on detention has to be
      made in the early phase of an influenza pandemic when information available about
      pathogenicity and other relevant information are limited. To date, sufficient
      evidence useful in making a decision as to detention has not been obtained. Under
      such circumstances, it is essential to make an optimum decision as to the
      necessity and means of detention based on assessment of multiple aspects and
      factors.

PMID- 21848205
TI  - [The effects of smoke-free environments on perception and behavior of university
      students, employees, and hospital visitors].

PMID- 21848206
TI  - [School health activities of yogo-teachers and functions of school health offices
      in Niigataken Chuetsu-oki earthquake. Qualitative analysis of interview data for
      yogo-teachers].

PMID- 21848207
TI  - [Factors determining frequency of social interaction in frail elderly
      individuals. A study of the elderly in urban environments].
AB  - OBJECTIVES: We examined the relationship between the frequency of social
      interaction and physical, psychological, and social functioning among frail, non
      housebound elderly to determine the best way to support social exchange and help
      prevent frail elderly from becoming housebound. METHODS: We recruited elderly
      individuals characterized as frail who lived in urban environments. A
      multidimensional examination was conducted that included interviews and physical
      performance tests. We defined an exchange as meeting and talking in person or
      talking by phone with friends, neighbors, relatives, or children living
      separately from the participants, and determined how many days a week frail
      elderly participants made contact with others. Independent variables were basic
      personality attributes; physical functioning, including eyesight, hearing, grip
      strength, masticatory force, ability to perform activities of daily living,
      walking ability, history of falls, and cognitive function; psychological
      functioning, including subjective health assessment, depression, and fear of
      falling; and social functioning, including ability to perform instrumental
      activities of daily living, social networks, and social activity. Multiple
      regression analysis was performed with SPSS 15.0 J to identify factors that could
      predict the frequency of contact with others. Data are expressed as mean +/-
      standard deviation. RESULTS: Of 61 elderly individuals recruited, 58 non
      housebound individuals were selected for our study (men, n = 12; women, n = 46;
      mean age, 81.2 +/- 6.0 years). We found that participants interacted with others
      4.5 +/- 2.0 days per week. For both male and female participants, the following
      independent variables were analyzed for the ability to predict frequency of
      contact with others: hearing (low-pitched sound), hearing (high-pitched sound),
      and scores on the Tokyo Metropolitan Institute of Gerontology (TMIG) index of
      competence. Multiple regression analysis revealed that hearing (low-pitched
      sound) and results of the TMIG index of competence significantly predicted
      frequency of contact with others for female participants. Specifically,
      participants without hearing loss and with a higher total score on the TMIG index
      of competence contacted others more frequently. CONCLUSION: Hearing and the
      ability to perform instrumental activities of daily living influence the
      frequency of contact with others. In particular, importance should be placed on
      hearing functions, which form the basis of communication. In addition to hearing
      evaluation and care (e.g., auditory test and hearing aid), maintaining the
      ability to perform instrumental activities of daily living is necessary to
      support social exchange.

PMID- 21848208
TI  - [Comparison of diagnostic criteria for the metabolic syndrome among Japanese
      university faculty].
AB  - OBJECTIVES: Diagnostic criteria for the metabolic syndrome (Mets) in Japan have
      been set by the Medical Committee of the Japanese Association of Medical Sciences
      (Med), the National Health and Nutrition Examination Survey (Nat), specific
      health checkups (Ckup), and second medical examination by Worker's Accident
      Compensation Insurance System (Wor). The purpose of this study was to compare
      classification of the metabolic syndrome by different organizational criteria and
      to investigate underlying differences. METHODS: All faculty members of a
      university in Osaka, Japan, underwent mandatory health checkups in September
      2008. The demographic distribution included 769 males (mean age, 49 +/- 12 years)
      and 415 females (mean age, 43 +/- 10 years). Using the Med, Nat, Ckup and Wor
      criteria, individuals were assessed for the MetS and pre-metabolic syndrome (pre
      Mets), strongly suspected metabolic syndrome (S-Mets) and assumed pre-metabolic
      syndrome (A-pre-Mets), as well as a positive support level (PSL) and a
      motivational support level (MSL). All faculty members were categorized into a
      morbid group (Mets, S-Mets, PSL, and FB) or a pre-morbid group (pre-Mets, A-pre
      Mets, and MSL) based on medical data and smoking habits. The incidence of morbid
      and pre-morbid individuals was compared across the four criteria and analyzed
      based on gender and age (under 40 and 40 or over). RESULTS: Male incidences for
      the morbid and pre-morbid classifications were 17% and 20% with Med, 9% and 23%
      with Nat, 27% and 14% with Ckup, and 1.4% and 0% with Wor. There were significant
      differences across criteria sets in both the morbid and pre-morbid groups, with
      significantly greater numbers of males than females, and higher prevalences in
      those aged 40 or over than in their younger counterparts. Males aged under 40
      classified into the pre-morbid group comprised 18% in Med, 16% in Nat, and 13% in
      Ckup. CONCLUSION: The different disease incidences found between Med and Ckup
      data in males aged 40 or over might be attributed to varying criteria for blood
      glucose levels, while Wor data may be influenced by the higher level of blood
      pressure set as a criterion with this approach. It will be important to
      continuously validate currently established criteria to identify the actual
      prevalence of MetS in Japan. Furthermore, incorporation of waist circumference
      and BMI for females, and a positive approach for young males, may be critical for
      future developments.

PMID- 21848209
TI  - [From the flight of Iu. A. Gagarin to the contemporary piloted space flights and
      exploration missions].
AB  - The first human flight to space made by Yu. A. Gagarin on April 12, 1961 was a
      crucial event in the history of cosmonautics that had a tremendous effect on
      further progress of the human civilization. Gagarin's flight had been prefaced by
      long and purposeful biomedical researches with the use of diverse bio-objects
      flown aboard rockets and artificial satellites. Data of these researches drove to
      the conclusion on the possibility in principle for humans to fly to space. After
      a series of early flights and improvements in the medical support system space
      missions to the Salyut and Mir station gradually extended to record durations.
      The foundations of this extension were laid by systemic researches in the fields
      of space biomedicine and allied sciences. The current ISS system of crew medical
      care has been successful in maintaining health and performance of cosmonauts as
      well as in providing the conditions for implementation of flight duties and
      operations with a broad variety of payloads. The ISS abounds in opportunities of
      realistic trial of concepts and technologies in preparation for crewed
      exploration missions. At the same, ground-based simulation of a mission to Mars
      is a venue for realization of scientific and technological experiments in space
      biomedicine.

PMID- 21848210
TI  - [Space flight and modeling experiments: new approaches to evaluation and
      prophylaxis].
AB  - The article dwells on the general issues of orthostatic tolerance and new
      impedance methods of orthostatic test evaluation in spaceflight and simulated
      microgravity. The results imply that OT requires adequate body hydration and
      functioning of volume-regulating hormones. New pharmacological compensators of
      orthostatic intolerance were tested in modeling experiments. It was shown that
      desmopressin and water-salt supplements retain body liquid and electrolytes
      during bed rest and improve tolerance of the orthostatic test Therefore,
      simultaneous control of the hydration status and OT can be best provided through
      physiologically reasonable prescription of synthetic ADH analogs.

PMID- 21848212
TI  - [Histogenesis of the liver of Japanese quail embryos developed in the conditions
      of microgravity].
AB  - The article reports the results of histogenetic studies of the liver extracted
      from Japanese quail embryos and hatchlings that had passed the embryonic and
      postnatal development in microgravity. Comparison of the liver from the flight
      and laboratory embryos showed identity of organogenesis and histogenesis
      processes in space and on Earth. However, it should be noted that early
      histogenetic development of the space embryo liver had been retarded which was
      concluded from an enlarged lumen in bile capillaries and loose arrangement of
      epithelium girders as compared with the control On day-10 post flight, the flight
      embryos exhibited liver induration through narrowing of sinusoids lumen.
      Haemopoietic zones became less numerous. By the end of embryonic development
      these histological differences of the flight and control liver disappeared
      essentially. Organogenesis and histogenesis of the liver obtained from the
      hatchlings that had spent 5 days in microgravity did not depart from the norm.
      However, inability of the birds to adapt to microgravity and ensuing starvation
      was the reason for dystrophic changes in the liver, venous congestion and
      increased histoleucocytic activity. All the liver changes faded away soon alter
      the hatchlings were settled in favorable life conditions

PMID- 21848211
TI  - [Tissue-specific reaction of the mucous coat of herbals' small gut under the
      influence of spaceflight factors on board biosat "Foton M3"].
AB  - Methods of light-optical microscopy, morpho- and cytometry and histochemisty were
      used to study the epithelial lining of herbal's small gut after 12-day flight in
      biosat "Foton M3". Changes in mucous coat histoarchitectonics included branching
      of villi and cystic lumps lined with prismatic epithelium. Shortening of the
      mucous membrane villi was accompanied by reduction of prismatic epithelium
      height, increase in the number of goblet cells and change of their dislocation,
      stimulation of excretion of biosynthesis products on the brush border surface
      pointing to impairment of the interstitial barrier function. Nothing evidenced
      change in mitotic index of the crypts epithelium in animals of the vivarium
      control, in the Kontur facility simulating the flight condition, and in the space
      flown herbals. There was a minor individual variability of changes in the
      epithelium mucous membrane due to the simulated flight factors.

PMID- 21848213
TI  - [Interrelation of dynamics of blood lipids and bone mineral density in humans
      during 370-day bed rest].
AB  - Comparison of bone mineral density and fatty-acid blood content in 9 human
      subjects exposed to 370-d bed rest revealed correlation of the loss in femoral
      neck density with parameters of lipid exchange. On day-46 of BR, the absolute
      lipids content in erythrocyte membranes and blood serum decreased considerably
      (1.5-2 times) when compared with baseline data. At the end of the experiment,
      lipids content in serum, on the contrary, surpassed baseline values 2-3 times:
      however, it remained lowered in erythrocyte membranes of the control group till
      day-280 of BR. Arachidonic acid correlated with prostaglandins PGE2 and PGF2alpha
      involved in regulation of osteoclasts and osteoblasts activities. Correlation of
      decreases in femoral neck density and unsaturated fatty acids in blood serum and
      erythrocyte membranes varied with the human subjects.

PMID- 21848214
TI  - [Dynamics of the body composition, neurohumoral and psychophysiological status of
      humans in the conditions of 105-day isolation and confinement].
AB  - Before, in and after the experiment with 105-day isolation and confinement, 6
      male volunteers from 25 to 40 years of age rationed NaCl and performed integral
      impedancimetric, psychological and hormonal investigations. Every 30 days blood
      collection for hormonal measurements was combined with filling of Cattell's 16
      personal factor questionnaire. Parameters of total body fluid, body mass, basic
      exchange, specific hydration and basic exchange were determined. The results
      showed that the experimental conditions did not affect significantly body
      composition, metabolism or neurohumoral regulation; the metabolic variations were
      largely associated with motivation for and value orientation in accommodation, to
      the permissible extent, of the controlled diet and work/rest schedule to personal
      needs. In addition, it was found that evolution of the psychophysiological status
      of humans in isolation and confinement is governed primnarily by personality
      characteristics and, to a less degree, specifics and length of exposure to the
      artificial environment; thus, in the opinion of the volunteers normoxic,
      normobaric and slightly hypercapnic (0.15-0.65% CO2) atmosphere was comfortable
      and harmless to health. Analysis of the whole data array verified the expressed
      interrelation of neuroendocrine and psychophysiological parameters as well as
      shifts in body basic exchange and mass, salt intake and hydration rate in the
      conditions of isolation and confinement.

PMID- 21848215
TI  - [Theoretical analysis of causes for prolonged delay of decompression sickness
      onset in divers].
AB  - The analysis of probable causes for anomalously prolonged latent time of
      developing decompression sickness in divers after completion of air dives was
      carried out in the content of the theory of formation and subsequent evolution of
      gas bubbles in body tissues. This phenomenon gives grounds to consider that
      certain of the decompression bubbles have a prolonged lifetime and gradually
      increase their affect on adjacent tissues. The main causes of increasing the
      lifetime of these bubbles are the increase of their sires due to the reduction of
      tissue perfusion during decompression and the coalescence them to one another, as
      well the encrustation of bubbles by a layer of intercellular fluid elements that
      reduces the rate of nitrogen diffusion from bubbles to tissues and retards their
      dissolution. The bubble layer decreases also the gas pressure inside bubbles due
      to reduction of the surface tension action of intercellular fluid that results in
      additional reduction of the diffusion flow of nitrogen from bubbles and the rate
      of their dissolution. Moreover, taken alone, the process of bubble layer
      formation seems as one of the main mechanisms of tissue lesions by gas bubbles.

PMID- 21848216
TI  - [Actiprotective and antihypoxic action of new heteroaromatic antioxidants].
AB  - Expernents with mice showed that most of 15 new heteroaromatic antioxidant
      compounds possess aciprotective and antixopixic properties. Based on results of
      treadmill and swimming tests, actiprotective action of IBKhF-1, 11 and 14
      surpassed greatly bemythil and bromanthane in ordinary conditions. Inhibitor of
      gluconeogenase tryptophan cancelled largely the stimulatting action of highly
      effective and active IBKhF-1, 2 and 11 on physical performance during treadmill
      exercise. Consequently, gluconeogenesis activation is one of the major components
      of the actiprotective action of these antioxidants. In addition, IBKhF-1, 11 and
      14 excelled bemythil and bromanthane in the extreme conditions of running in
      hyperthermia and swimming in acute hypoxia combined with hypercapnia. IBKhF-2 and
      14 were better than amtisol (standard antihypoxic agent) and bemythil against
      acute hypoxia in pressure chamber, whereas IBKhF-4 and 14 excelled these agents
      in thermal chamber.

PMID- 21848217
TI  - [Elevated air temperatures tolerance of chufa (Cyperus esculentus L.), a
      phototroph component of life support systems].
AB  - Resistance of biotechnical life support systems (BTLSS) to stress-factors
      depends, in addition to some other conditions, on tolerance of higher plants as
      part of the photosynthesizing component. Purpose of the investigations with chufa
      Cyperus esculentus L. cultivation on mineralized solid and liquid human wastes
      (according to Yu. Kudenko) was to test plant tolerance of air temperature rise to
      45 degrees C. Tolerance was assessed as a function of nitrogen form in nutrient
      solutions and PAR intensity during thermal shock. PAR intensity was controlled at
      150 W/m2 and air temperature--at 25 degrees C. Thermal shock was induced in 30
      day plants with PAR = 150 or 250 W/m2. Twenty hours at 45 degrees C did not cause
      irreversible damage of the plant photosynthetic apparatus. Higher PAR intensity
      (250 W/m2) and nitrates in nutrient solution mitigates substantially the damaging
      effect of the stress factor

PMID- 21848218
TI  - [Procedure of running experiments on studying the effects of altered gas medium
      on culture of hydra Hydra attenuata].
AB  - Owing to the simple form and short gemmation, hydroid polyps have become a
      classic model object for studies into cell division and proliferation, and
      effects of changed environment on these processes. However, there is no procedure
      for studying of how altered gas composition of aqueous medium affects biological
      processes in hydroidpolyps. Testing of a procedure for objective studies with
      bioculture of Hydra attenuata resulted in determination of optimal hydra density
      in Petri dish. It was also stated that culture duplication takes minimal time at
      25-30 degrees C. Tests verified efficiency of an incubator designed for
      experiment with Hydra attenuata in pressurized chambers enabling controlled
      ventilation by different gas mixtures. It was shown that time of culture
      duplication in normoxic and hypoxic nitrox is permanent and statistically
      different Therefore, the proposed procedure and incubator can be useful for
      fundamental and applied studies of the biological effects of altered gas medium
      on hydroid polyps.

PMID- 21848219
TI  - [Interrelation between cardiac pump function disturbances and cardiac
      contractility after beta-adrenergic hyperstimulation of the heart in rats].
AB  - The complex of structural and functional changes of myocardium was investigated
      in experiments with rats with chronic beta-adrenergic activation for 1 month. We
      observed substantial attenuation of myocardial pump function, particularly
      reduction of stroke volume by 38.50% (P < 0.01), cardiac output by 42.38% (P <
      0.01), and ejection fraction by 35.61% (P < 0.01). Furthermore, 2-fold increase
      of end-diastolic left ventricular pressure (P < 0.01) and rise of active
      relaxation constant Tau by 12.91% (P < 0.05) were observed. This indicates on an
      impaired diastolic function of the heart that is associated with accumulation of
      connective tissue elements in myocardium and increase of its end-diastolic
      stiffness that finally leads to cardiac pump function disturbances. Surprisingly,
      myocardial contractility was considerably augmented not only after the treatment
      with beta-adrenergic agonist but also on the 26th day after drug cessation. This
      phenomenon is associated with elevation of dP/dt(max) by 49.9% (P < 0.01), 2.5
      fold increase of end-systolic elastance (P < 0.01) as well as maximal myocardial
      elastance by 42.53% (P < 0.05). It can be explained by compensatory influence of
      increased contractility that nevertheless failed to maintain adequate cardiac
      pump function and furthermore it may result in depletion of cardiac energy
      resource.

PMID- 21848220
TI  - [Effects of amixine on electrophoretic mobility of murine T lymphocytes].
AB  - The amixine-induced early changes in the electrophoretic mobility (EPM) of murine
      splenic T lymphocytes were studied in vitro by the microelectrophoresis
      technique. It has been found that T lymphocytes treated with amixine have a
      greater EPM within the first hours of amixine addition than control cells. This
      change in EPM depends on the concentration of amixine in the medium and the
      duration ofamixine exposure. It was concluded that the amixine-treated cells have
      a greater net negative surface charge density than control cells. This effect may
      play an important role in the cell-cell interaction during the immune response.

PMID- 21848221
TI  - [Correction of lipid peroxidation and antioxidant system disorders by
      bioflavonoids during modeling of cholesterol atherosclerosis in rabbits].
AB  - We have studied the influence of bioflavonoids (quercetin, corvitin) on lipid
      peroxidation and antioxidant enzymes in the modeling of cholesterol
      atherosclerosis in rabbits. It has been shown that simultaneous administration of
      the quercetin derivative corvitin suppressed lipid peroxidation. We showed that
      under hypercholesterolemia, the concentration of malone dialdehyde in myocardial
      tissue in rabbits is significantly increased, while administration of
      bioflavonoids decreased the concentration of malone dialdehyde by 38.3%.
      Furthermore, corvitin caused activating effects on antioxidant enzymes superoxide
      dismutase and catalase in cardiac tissue. Our data suggest that bioflavonoids are
      able to suppress lipid peroxidation and prevent the decrease ofantioxidant
      enzymes activity in rabbits with cholesterol-rich diet induced atherosclerosis.

PMID- 21848222
TI  - [Effect of chronic stress during puberty on the reproductive system of female
      rats with experimental hyperandrogenicity].
AB  - Effects of chronic stress (daily 30-min immobilization) on 35-45 days of life and
      its combination with androgenization (implantation of testosterone-containing
      capsules on 33rd day of life) on reproductive system of 2.5 month old female rats
      were studied. The term of sexual maturation, estrous cycles regularity and
      structure, blood plasma levels of testosterone, progesterone and androstenedione
      as well as ovarian histology were examined. Androgenization resulted in the blood
      plasma testosterone level increase and the androstenedione level decrease,
      development of oligo- or anovulatory condition characterized by disorders or
      discontinuation in estrous cyclicity. We also detected abrupt reduction or
      absence of postovulatory luteal bodies, cysts formation and ovarian interstitial
      tissue overgrowth. All experimental animals had normal blood plasma
      corticosterone level. Stressed rats had no considerable changes in reproductive
      system except of some cyclicity disorders. Stressed against androgenization rats
      demonstrated delayed pubescence, an increased number of ovarian cysts along with
      attenuation ofandrogenization-caused negative effects on the sexual cyclicity.

PMID- 21848223
TI  - [Metabolic activity of neutrophilic granulocytes and possible ways of its
      correction in patients with acute coronary syndrome].
AB  - The present study aimed to investigate the metabolic activity of neutrocytes and
      the action of corvitin on the level of superoxide anion and myeloperoxidases of
      cells in vitro with the calculation of index of consumption of myeloperoxidase in
      patients with ST-elevation acute coronary syndrome. Patient were divided into 2
      groups according to the level of superoxide anion. Group 1 included the patients
      (68%) with the initially low level of superoxide anion, and adding of corvitin to
      the cells of such patients promoted normalization of this index. In this group we
      observed also neutrocytosis, low index of consumption of myeloperoxidase and a
      high level of this enzyme in general population of neutrocytes. Group 2 included
      patients (32%) with initially normal level of superoxide anion. In this group,
      corvitin did not influence substantially this factor. Such patients had a level
      ofmyeloperoxidase within control values and the index of consumption of this
      enzyme was also within control values. The analysis of hospital period showed
      that the patients of group 1 had a higher frequency of ventricular
      tachycardia/ventricular fibrillation, paroxysms of atrial fibrillation, bundle
      branch blocks and worsening of the kidney function. We suppose that a low level
      of superoxide anion in neutrocytes play a major role in the development of
      complications in patients with acute coronary syndrome. An intravenous
      administration of corvitin was effective in restoring the metabolic activity of
      neutrocytes.

PMID- 21848224
TI  - [Comparative characteristic of energy supply disturbances in arterial and venous
      walls of rabbits with alloxan diabetes and monoiodacetate intoxication].
AB  - We showed here that energy metabolism in thoracic rabbit aorta and posterior vena
      cava is disturbed two weeks following the induction of alloxan-induced diabetes
      and monoiodacetate intoxication. In the vessels studied, the alterations are
      manifested in the decrease in the intensity of glucose uptake, oxygen
      consumption, lactic acid production, and ATP resynthesis. Simultaneously, the ATP
      content is significantly reduced. The possible significance of these disorders in
      the development of Monckeberg's arteriosclerosis is discussed.

PMID- 21848225
TI  - [The changes in mental working capacity of operators during 24-hour shift work
      conditions].
AB  - Psychophysiological peculiarities of influence of a 24-hour shift work on the
      efficiency of operators have been discussed. It was shown that servicemen
      operators develop significant fatigue as a result of 24 hrs duty services. The
      informative psychophysiological characteristics which can be reliable indicators
      of fatigue level are highlighted. Individual psychophysiological indicators of
      fatigue level, according to different mechanisms of its development, have been
      proposed. The hypothesis about the existence of several compensatory mechanisms
      for maintenance of long duty operators' working capacity has been formulated.

PMID- 21848226
TI  - [Age-dependent peculiarities of functional state of the cardiovascular system in
      children with cerebral palsy].
AB  - The age-dependent peculiarities of the functional state of the cardiovascular
      system (CVS) in children of 7-9 years old with cerebral palsy (CP) with
      moderately marked functional disorders have been studied. Statistically
      significant age difference in multiple indicators of central circulation has been
      detected. Age-dependent peculiarities of hemodynamic response in children with CP
      in response to dosed physical load have been revealed. The adaptive capacity of
      the CVS was calculated by the method of comparative analysis of the amplitude and
      the variation heart rate monitoring. We found that 38% of the studied children
      had a high level of adaptive capacity of the CVS, while 50% of the children had a
      low level of adaptive capacity of the CVS.

PMID- 21848227
TI  - [Significance of adreno- and cholino-inhibitors in cardiac rhythm autonomic
      regulation during different weather types].
AB  - In the experiments of 4.5-5 months old rats, we studied the influences of adrenal
      and cholinoblockators on the autonomic balance of cardiac rhythm during the I, II
      and III types of weather. Blockade of beta-adrenoreceptors and M-cholinoreceptors
      was evoked by anapriline (1.5 mg/kg) and atropine sulfate (1.0 mg/kg),
      respectively. Electrocardiograms for further analysis were registered in control
      and 30 minutes after injections of the blockers. It was shown that male rats have
      the highest activity of sympathetic nervous system under weather type I. High
      reactivity of beta-adrenoreceptors was determined under all weather types in
      males and females. In males, atropine blocks the autonomic M-cholinoreceptors
      under weather types II and III, while in females this effect is detected under
      all weather types. Furthermore, in males we detected a compensatory increase of
      sympathetic nervous system during all weather types, while in females such an
      increase was detected during weather types I and II. Collectively, we determined
      sex differences in adaptation to weather type changes which are connected to
      different reactivity of adreno- and cholinoreceptors.

PMID- 21848228
TI  - [Functional characteristics of human neuro-muscular system and their changes as a
      result of mechanical unloading of different duration].
AB  - This study examined the effects of short- (1-, and 3-day) and long-term (7-day)
      'dry' immersion (DI) on neuromuscular function of human the triceps surae muscle.
      The isometric twitch tension (Pt) decreased by 8.7% after 1-days, but increased
      by 11.5 and 9.8 % after 3- and 7-days DI, respectively. Maximal voluntary
      contraction (MVC) decreased by 13.6, 19.7, and 33.8% after 1-, 3-, and 7-days DI,
      respectively (p < 0.05-0.01), electrically evoked (frequency of 150 impulses x s(
      1)) tetanic tension (Po) reduced by 1.8, 5.3, and 8.2%, respectively,
      (nonsignificant). The difference between Po and MVC expressed as a percentage of
      Po and referred to as force deficiency (Fd) was also calculated. Fd increased by
      23.4, 20.2, and 78.7% after 1-, 3-, and 7-days, respectively (p < 0.05-0.001).
      After DI, the time-to-peak tension (TPT), half-relaxation time (1/ 2 RT), and
      total contraction time (TCT) was reduced. The TPT decreased by a mean value of
      8.5, and 3.3% after 1- and 3-days, respectively, and after 7-day did not reveal
      significant changes in the curve of the TPT. 1/2 RT and TCT was shorter in the
      post-immersion condition than in the control value. The rate of increase of
      voluntary contraction calculated according to relative scale was significantly
      reduced after DI (p < 0.05-0.001), but for the electrically evoked contraction
      (frequency of 150 impulses x s(-1)) there were no substantial changes from the
      initial physiological state. A standard 2-min fatigue of electrically-induced
      intermittent test (frequency of 50 impulses x s(-1)) did not differ substantially
      from the initial physiological state, but the electrical M-waves reduced
      significantly. The relative extent of the decline in either of these two
      parameters can be determined from the change in the relation of the electrical M
      wave to the contractile response (the E/C ratio). After long-term DI (7 day) of
      muscle a significantly greater decline of electrical waves is observed as
      compared to contractile response by a short-term DI (1-, and 3-day),
      respectively.

PMID- 21848229
TI  - [Effect of vitamin C on the condition of NO-synthase system in experimental
      stomach ulcer].
AB  - We investigated the effect of Vitamin C (Vit C) on the changes of activity of the
      enzymes of NO-synthase system, nitric oxide content, lipoperoxidation processes,
      activity of SOD and catalase in gastric mucosa (GM), and concentrations of L
      arginine, Vit C and Vit E in the blood of rats under conditions of experimental
      ulcer of the stomach caused by adrenaline injection. Vit C displayed a pronounced
      antioxidant action, reduced the degree of destructive affections, diminished the
      activity of iNOS and lipoperoxidation processes, decreased the NO content and SOD
      activity. Furthermore, the concentration of L-arginine and Vit C in the blood was
      increased. Combined action of Vit C with L-arginine reduced the degree of GM
      lesions, activity of eNOS and the content of NO in GM whereas the concentration
      of L-arginine in blood was increased. Under conditions of Vit C action and iNOS
      and COX-2 blockage, the activity of NO-synthases and lipoperoxidation processes
      were slightly decreased, indicating on dominant action of Vit C.

PMID- 21848230
TI  - [The influence of a low-frequency current electromagnetic field on prenatal
      development].
AB  - The influence of a low-frequency current electromagnetic field on prenatal
      processes of chick embryos development was investigated. Considering multiple
      external factors influencing the result, three incubations have been performed.
      By triple processing during 1 minute (for 9th, 12th and 15th incubation days),
      the deductibility of eggs raises, the time of incubation and output duration is
      reduced, decreases death rate of embryos during the incubation.

PMID- 21848231
TI  - [Choice of the surgical approach for implantation of a left ventricular lead by
      the data of prolonged coronaroangiography].
AB  - Effectiveness of prolonged coronarography was assessed for investigation of
      venous heart anatomy with reference to etiology of the disease and heart chamber
      sizes. It was shown that lesions of the coronary arteries and morphometrical
      indices of the heart did not influence the heart venous anatomy. A detailed
      analysis of patients with ischemic heart disease and anamnesis of myocardial
      infarction has revealed the absence of the heart vein in the zone of old
      myocardial infarction. At the preoperative stage the placement of a cardiac
      resyncronising device the integration of data of EchoKG, prolonged
      coronaroangiography and others allows determination of the possible surgical
      method of placing the lead to the left ventricle of the heart. The algorithm of
      the method of decision on the placement of the left ventricular lead has been
      developed, investigated and introduced into clinical practice.

PMID- 21848232
TI  - [Regional chemoinfusion and radiation therapy to patients with breast cancer
      metastases to the brain: preliminary results].
AB  - Effectiveness and safety of regional chemoinfusion in combination with radiation
      therapy in patients with breast cancer with metastases to the brain was
      clinically assessed. Cerebral angiography with chemoinfusion was fulfilled in six
      patients. The procedure could not be fulfilled completely in one patient because
      of transient vascular and neurological disorders. In the other five patients the
      regional superselective chemoinfusion was fulfilled successfully to the arteries
      feeding the metastatic foci in the brain with Carmustin in dosage 100 mg in
      combination with radiation therapy that was fulfilled in all six patients before
      the planned total focal dose. The incomplete response (n=5) to the treatment and
      stabilization of the process (n=l) were noted in six observations.

PMID- 21848233
TI  - [Cytoreductive operations in complex treatment of patients with intrapulmonary
      metastases of colorectal carcinoma].
AB  - An analysis of results of treatment of 112 patients with metastases of
      intrapulmonary colorectal carcinoma (CRC) for the period from 1990 to 2006 has
      shown that cytoreductive opera tions for excision of the metastases are an
      effective method of treatment of this category of patients which allows a two
      times increased survival median as compared with analogous index in the group of
      patients exposed to palliative chemotherapy. Palliative chemotherapy fails to
      have statistically significant influence to survival of patients who have ablated
      intrapulmonary CRC metastases in the volume of complete cytoreduction.

PMID- 21848234
TI  - [First experience with minilaparotomy for Leriche syndrome].
AB  - The authors present the first experience with reconstruction of the terminal part
      of the infrarenal aorta from minilaparotomy. There were 11 aortofemoral
      bifurcation shunts in patients with Leriche syndrome. In two cases conversion
      (general calcification of the aorta, visceral obesity) was necessary. Regression
      of extremity ischemia was obtained in all the patients.

PMID- 21848235
TI  - [Monitoring of intraabdominal pressure in colonic obstruction].
AB  - Results of surgical treatment of 197 patients with acute colonic obstruction
      complicated by intraabdominal hypertension were analyzed. Monitoring of
      intraabdominal pressure was made in 101 patients at the pre- and postoperative
      periods. Compensated, sub- and decompensated forms of obstruction depending on
      the data of intraabdominal pressure were determined. The level and dynamics of
      the intraabdominal pressure are taken as criteria of severity of acute colonic
      obstruction, decision on the time and volume of surgical procedures. The medico
      diagnostic algorithm of management of such patients is proposed. Lethality turned
      out to be decreased to 15.8% as compared with a control group (24%) due to the
      monitoring of intraabdominal pressure and improved surgical strategy.

PMID- 21848236
TI  - [Operative treatment and diagnostics of Zenker diverticulum using modern
      endoscopic technique].
AB  - The authors present results of examination and treatment of 272 patients with
      Zenker diverticulums of different localization. Features and problems in
      fibroesophagoscopy in patients with Zenker diverticulum are discussed. Surgical
      interventions with endoscopic assistance were fulfilled in 37 patients with
      diverticulum. A new way of endoscopic management of Zenker diverticulum using
      preparation "Disport" and the method of endoscopic incision of cricofaringeal
      muscle are proposed. Good clinical results of the treatment were obtained.

PMID- 21848237
TI  - [Proximal limits of resection and the role of mediastinal lymph dissection in
      surgical treatment of gastroesophageal cancer].
AB  - An analysis of results of treatment of 37 patients allowed a conclusion that
      differential approach is possible in choice of the level of resection of the
      esophagus in patients with gastroesophageal cancer (GEC). Resection of the
      esophagus within the limits of 2-3 cm from the proximal edge of the tumor can be
      performed for GEC in the absence of data of spread of the tumor outsides the
      limits of the organ wall and pronounced lymphogenic dissemination. Extension of
      the resection limits to 4 cm and more is necessary in performing radical
      operations in patients with late stages of the disease. Ablation of the lymph
      nodes of the lower mediastinum is a necessary component of radical operative
      interventions in treatment of patients with GEC.

PMID- 21848238
TI  - [Specific formation of esophageal autotransplant in the compromized and resected
      stomach].
AB  - An experience with 60 operated patients allows introduction of accuracy in the
      idea of possibility to use the compromised with different diseases and surgical
      procedures stomach in plasty of the esophagus. Technical specific features of
      forming the transplant are developed. Practicability of esophageal plasty with
      the small bowel using the loop of the bowel involved in digestive anastomoses is
      shown. In nonstandard situations the success of surgery is determined by an
      individual choice of plastic material, using reconstructive vascular surgery and
      rational method of placing the transplant.

PMID- 21848239
TI  - [Results of one-stage reconstruction of anal sphincter in surgical treatment of
      fistulas-in-ano combined with fecal incontinence].
AB  - The investigation included 20 patients. Mean index of the severity of
      incontinence before operation by the Wexner scale was 9.3+/-2.4 scores. After
      radical dissection of the fistula and sphincter plasty in 7 patients (the first
      group) the wound of the rectum mucosa was sutured in longitudinal direction, in
      13 patients (the second group) the rectum wall graft was brought down to the edge
      of the created anal canal. Uncomplicated post-operative period was noted in 15
      (75%) patients. Suppuration of the wound developed in 3 (42.9%) patients of the
      first group and in 2 (15.3%) patients of the second group. The index of
      incontinence severity decreased to 2.4+/-1.1% scores (reduction of 4.5 scores in
      the first group and 7.7 scores in the second group).

PMID- 21848241
TI  - [Main trends and controversies in treatment of patients with diffuse toxic goiter
      and thyroid gland cancer].

PMID- 21848240
TI  - [Prophylactics and treatment of postoperative hernias of the lateral abdominal
      walls using polypropylene endoprosthesis].
AB  - An analysis of complex examination and treatment of 151 patients after planned
      and performed surgical interventions on organs of the retroperitoneal space was
      made. The patients were divided into 4 groups. The first group (of comparison)
      included 46 patients who were treated by lumbotomy for different diseases of
      organs of the urinary system. In 35 patients of the second group (prophylactics)
      the indications were determined and in 20 patients preventive endoprosthesis of
      the lateral abdominal wall using polypropylene endoprosthesis was fulfilled.
      Herniotomy with plasty of the lateral abdominal wall using local tissues was
      fulfilled in 30 patients. Prosthesing hernioplasty of the lateral abdominal wall
      was fulfilled in 40 patients of the main group. It was found that preventive
      endoprosthesis of the lateral abdominal wall allowed prevention of progressing
      anatomo-functional i/isufficiency and the appearance of postoperative hernias.
      The application of polypropylene endoprosthesis for the treatment of
      postoperative hernias allows obtaining 36.4% more good results as compared with
      the control group, 21.7% decreased number of satisfactory results and no
      recurrent hernias.

PMID- 21848242
TI  - [Features of hemocomponental therapy in oncological patients].
AB  - The authors present an analysis of specific features of transfusions of
      erythrocyte containing media in oncological patients. Special attention was given
      to necessary selection of donor erythrocytes in performing operations with
      massive intraoperative blood loss. It considerably contributes to a decreased
      number of posttransfusional reactions and complications. For the recent five
      years transfusions of erythrocyte containing media to more than 15 thousand
      patients with surgical treatment were analyzed. Among them the individual
      selection of donor blood was fulfilled in 2047 cases. Compatible erythrocytes
      could not be selected in five cases only. In these patients infusions of
      Perftoran were used as an oxygen carrier both during operation and at the
      postoperative period.

PMID- 21848243
TI  - [Comparative assessment of national and foreign endoprostheses for hernioplasty].
AB  - The used foreign endoprostheses have redundant strength, and great number and
      stiffness of implanted material might be a cause of complications and result in
      patients' discomfort associated with decreased mobility of the anterior abdominal
      wall. Less material consumption of endoprostheses results in increased porosity
      and less thickness facilitating rapid integration of the grid into the elastic
      and strong connective tissue scar. Company "Lintex" has developed and produced
      endoprostheses from polypropylene and polyvinylenfluoride monothreads in heavy,
      standard and light version, which allows their choice with a glance to the
      particular surgical situation.

PMID- 21848244
TI  - [On the question of heart injuries].
AB  - The work is devoted to an analysis of hospitalized patients to the specialized
      department of injuries of the chest and abdomen of the Mariinskaja hospital at
      the period from 1993 through 2010. The diagnosis of injury of the pericardium and
      heart had 280 patients, during the operative treatment heart injuries were
      detected in 156 (55.71%) patients. Penetration to the heart chambers was found in
      132 (84.61%) of them, with perforating and multiple injuries there were 24
      (15.39%) patients. Operations were performed during 20 minutes after admission on
      65 (28.9%), and during the following two hours on 160 (71.1%) patients. Expectant
      management and conservative treatment were used in treatment of 34 patients
      (12.14%), three patients were admitted in the state of apparent death and died
      during 15 minutes. The lethality of 41 patients was 26.28%. mainly it was those
      who were operated at the period from 80 to 100 minutes from the moment of injury.
      The success of treatment depends on the early hospitalization, correct diagnosis
      and emergent surgery.

PMID- 21848245
TI  - [Choice of approach trajectories in stereotaxic surgery in patients with
      intracerebral tumors].
AB  - An analysis of factors was made which influence the choice of approach
      trajectories in preoperative planning the diagnostic and medical stereotaxic
      interventions in patients with intracerebral tumors. Stereotaxic operations were
      planned and fulfilled on 124 patients with glial tumors of different
      supratentorial localizations. In planning trajectories with using MRI the passage
      of stereotaxic cannula through the pial folds and functionally significant zones
      of the brain were avoided. At the postoperative period no parenchymatous
      hemorrhages were noted in the approach zone, even with great number of
      trajectories. It was also noted that in passing the stereotaxic instrument
      through the lateral venticles of the brain the risk of complications was minimal.

PMID- 21848246
TI  - [Initial experience of using XperCT in neurosurgery].
AB  - Modern angiographic complexes allow performing emulation of computed tomography
      (CT). Comparison of the resolving power of XperCT and CT indicated sufficient
      sensitivity of the new technology in detection of focal lesions of the brain, the
      possibility of its application in interventional neuroradiology. The application
      of XperGuide allows control the position of the instrument during operation
      directly without using additional equipment of moving the patient. The
      application of XperGuide decreases the risk of intra- and early postoperative
      complications.

PMID- 21848247
TI  - [Causes and results of repeated videothoracoscopy].
AB  - For 7 years videothoracoscopies for diseases and traumas of the chest were
      fulfilled in 2075 patients, abscessoscopy in 27 patients. Repeated
      videothoracoscopies were fulfilled in 41 (2%) patients operated for spontaneous
      pneumothorax, pleural empyema, exudative pleurisy and injuries to the chest due
      to recurrent hydropneumothorasx, prolonged abundant release by drainage,
      bleedings by drainage or formation of clotted hemothorax, not effectiveness of
      sanation, of the empyema cavity, reabscessoscopy - in 2 patients.
      Revideothoracoscopies were divided into groups with the presence of drainages or
      removed drainages according to the terms - into emergent (on the first day,
      immediately after the development of complications), urgent (from 2 to5 days),
      postponed (from 6 to 15 days), and late (more than 15 days). In 4 cases the
      conversion to minithoracotomy had to be done due to continuing bleeding, the
      absence of lung hermetism. All patients with spontaneous pneumothorax, pleuritis
      and chest trauma recovered. Lethal outcome was in 1 (2.4%) case from lung artery
      thromboembolism. It was concluded that revideothoracoscopy was an alternative
      thoracotomy of full value in reinterventions.

PMID- 21848248
TI  - [Endoscopic methods of hemostasis in treatment of Mallory-Weiss syndrome].
AB  - Results of treatment of Mallory-Weiss syndrome using endoscopic methods of
      hemostasis in 549 patients were analyzed. The patients were divided into two
      groups: in 2000-2004 years without endoscopic methods, in 2004-2008 years using
      the endoscopic methods in the diagnostics and treatment. Considerably decreased
      operative activity and death rate was established in cases of treatment with
      endoscopic methods.

PMID- 21848249
TI  - [Long-term results of endoprosthesis of the hip joint with Plus-Endoprosthetic
      prosthesis].
AB  - An experience and results with using endoprosthesis of the hip joint with Plus
      Endoprosthetic prosthesis in 937 (1018 operations) patients were analyzed. The
      period of follow-up observations was 12 years. Distinctive characteristics of the
      endoprosthesis are described. Specific behavior of this construction in patients
      with diseases and damages of the hip joint are shown. Results and complications
      of the endoprosthesis operations are analyzed. In whole, excellent and good
      results were obtained in 99.42% of cases, satisfactory - in 0.47%, unsatisfactory
      - in 0.11%.

PMID- 21848250
TI  - [Favorable outcome of treatment of a patient with recurrent cysto-virsungo
      intestinal bleedings].

PMID- 21848251
TI  - [Surgical correction of acquired valvular disease in Saint Petersburg].

PMID- 21848252
TI  - [Hemostasis in abdominal sepsis].

PMID- 21848253
TI  - [Use of loop thromboendarterectomy in iliac-femoropopliteal arterial segment:
      contemporary state of the problem].

PMID- 21848254
TI  - Development of an immunoaffinity chromatography purification and ultra
      performance liquid chromatography tandem mass spectrometry method for
      determination of 12 sulfonamides in beef and milk.
AB  - A highly selective and sensitive method was developed for the simultaneous
      determination of 12 sulfonamides in beef and milk by immunoaffinity
      chromatography purification coupled to ultra performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS). The MS/MS conditions, UPLC mobile phase,
      injection solution, sample purification process, and matrix effect were studied
      to optimize the operating conditions. The limits of detection (LODs) of the
      instrument for the studied sulfonamides ranged from 0.4 to 2.0 MUg L(-1), being
      1.6-8.0 MUg kg(-1) for beef and 1.8-6.4 MUg kg(-1) for milk. The standard
      solution was diluted with blank beef or milk matrix for the construction of
      calibration curves, which had a linear range from 10 to 200 MUg kg(-1) and
      regression coefficients higher than 0.990 (n=10) for all the studied
      sulfonamides. Samples spiked at 10, 20, and 100 MUg kg(-1) showed recoveries
      above 70% and relative standard deviations below 10%.

PMID- 21848255
TI  - Whole-body rocking motion of a fusion peptide in lipid bilayers from size
      dispersed 15N NMR relaxation.
AB  - Biological membranes present a highly fluid environment, and integration of
      proteins within such membranes is itself highly dynamic: proteins diffuse
      laterally within the plane of the membrane and rotationally about the normal
      vector of this plane. We demonstrate that whole-body motions of proteins within a
      lipid bilayer can be determined from NMR (15)N relaxation rates collected for
      different-sized bicelles. The importance of membrane integration and interaction
      is particularly acute for proteins and peptides that function on the membrane
      itself, as is the case for pore-forming and fusion-inducing proteins. For the
      influenza hemagglutinin fusion peptide, which lies on the surface of membranes
      and catalyzes the fusion of membranes and vesicles, we found large-amplitude,
      rigid-body wobbling motions on the nanosecond time scale relative to the lipid
      bilayer. This behavior complements prior analyses where data were commonly
      interpreted in terms of a static oblique angle of insertion for the fusion
      peptide with respect to the membrane. Quantitative disentanglement of the
      relative motions of two interacting objects by systematic variation of the size
      of one is applicable to a wide range of systems beyond protein-membrane
      interactions.

PMID- 21848256
TI  - Cosolvent gel-like materials from partially hydrolyzed poly(vinyl acetate)s and
      borax.
AB  - A gel-like, high-viscosity polymeric dispersion (HVPD) based on cross-linked
      borate, partially hydrolyzed poly(vinyl acetate) (xPVAc, where x is the percent
      hydrolysis) is described. Unlike hydro-HVPDs prepared from poly(vinyl alcohol)
      (PVA) and borate, the liquid portion of these materials can be composed of up to
      75% of an organic cosolvent because of the influence of residual acetate groups
      on the polymer backbone. The effects of the degree of hydrolysis, molecular
      weight, polymer and cross-linker concentrations, and type and amount of organic
      cosolvent on the rheological and structural properties of the materials are
      investigated. The stability of the systems is explored through rheological and
      melting-range studies. (11)B NMR and small-angle neutron scattering (SANS) are
      used to probe the structure of the dispersions. The addition of an organic liquid
      to the xPVAc-borate HVPDs results in a drastic increase in the number of cross
      linked borate species as well as the agglomeration of the polymer into bundles.
      These effects result in an increase in the relaxation time and thermal stability
      of the networks. The ability to make xPVAc-borate HVPDs with very large amounts
      of and rather different organic liquids, with very different rheological
      properties that can be controlled easily, opens new possibilities for
      applications of PVAc-based dispersions.

PMID- 21848257
TI  - Measuring the partitioning kinetics of membrane biomolecules using patterned two
      phase coexistant lipid bilayers.
AB  - We report a new method for measuring the partitioning kinetics of membrane
      biomolecules to different lipid phases using a patterned supported lipid bilayer
      (SLB) platform composed of liquid-ordered (lipid raft) and liquid-disordered
      (unsaturated lipid-rich) coexistent phases. This new approach removes the
      challenges in measuring partitioning kinetics using current in vitro methods due
      to their lack of spatial and temporal control of where phase separation occurs
      and when target biomolecules meet those phases. The laminar flow configuration
      inside a microfluidic channel allows us to pattern SLBs with coexistent phases in
      predetermined locations and thus eliminates the need for additional components to
      label the phases. Using a hydrodynamic force provided by the bulk flow in the
      microchannel, target membrane-bound species to be assayed can be transported in
      the bilayers. The predefined location of stably coexistent phases, in addition to
      the controllable movement of the target species, allows us to control and monitor
      when and where the target molecules approach or leave different lipid phases.
      Using this approach with appropriate experimental designs, we obtain the
      association and dissociation kinetic parameters for three membrane-bound species,
      including the glycolipid G(M1), an important cell signaling molecule. We examine
      two different versions of G(M1) and conclude that structural differences between
      them impact the kinetics of association of these molecules to raft-like phases.
      We also discuss the possibilities and limitations for this method. One possible
      extension is measuring the partitioning kinetics of other glycolipids or lipid
      linked proteins with posttranslational modifications to provide insight into how
      structural factors, membrane compositions, and environmental factors influence
      dynamic partitioning.

PMID- 21848258
TI  - Theoretical analysis of the spin Hamiltonian parameters in Co(II)S4 complexes,
      using density functional theory and correlated ab initio methods.
AB  - A systematic Density Functional Theory (DFT) and multiconfigurational ab initio
      computational analysis of the Spin Hamiltonian (SH) parameters of tetracoordinate
      S = 3/2 Co((II))S(4)-containing complexes has been performed. The complexes under
      study bear either arylthiolato, ArS(-), or dithioimidodiphosphinato,
      [R(2)P(S)NP(S)R'(2)](-) ligands. These complexes were chosen because accurate
      structural and spectroscopic data are available, including extensive Electron
      Paramagnetic Resonance (EPR)/Electron Nuclear Double Resonance (ENDOR) studies.
      For comparison purposes, the [Co(PPh(3))(2)Cl(2)] complex, which was thoroughly
      studied in the past by High-Field and Frequency EPR and Variable Temperature,
      Variable Field Magnetic Circular Dichroism (MCD) spectroscopies, was included in
      the studied set. The magnitude of the computed axial zero-field splitting
      parameter D (ZFS), of the Co((II))S(4) systems, was found to be within ~10% of
      the experimental values, provided that the property calculation is taken beyond
      the accuracy obtained with a second-order treatment of the spin-orbit coupling
      interaction. This is achieved by quasi degenerate perturbation theory (QDPT), in
      conjunction with complete active space configuration interaction (CAS-CI). The
      accuracy was increased upon recovering dynamic correlation with
      multiconfigurational ab initio methods. Specifically, spectroscopy oriented
      configuration interaction (SORCI), and difference dedicated configuration
      interaction (DDCI) were employed for the calculation of the D-tensor. The sign
      and magnitude of parameter D was analyzed in the framework of Ligand Field
      Theory, to reveal the differences in the electronic structures of the
      investigated Co((II))S(4) systems. For the axial complexes, accurate effective g'
      tensors were obtained in the QDPT studies. These provide a diagnostic tool for
      the adopted ground state configuration (+/-3/2 or +/-1/2) and are hence
      indicative of the sign of D. On the other hand, for the rhombic complexes, the
      determination of the sign of D required the SH parameters to be derived along
      suitably constructed symmetry interconversion pathways. This procedure, which
      introduces a dynamic perspective into the theoretical investigation, helped to
      shed some light on unresolved issues of the corresponding experimental studies.
      The metal hyperfine and ligand super-hyperfine A-tensors of the C(2)
      [Co{(SPPh(2))(SP(i)Pr(2))N}(2)] complex were estimated by DFT calculations. The
      theoretical data were shown to be in good agreement with the available
      experimental data. Decomposition of the metal A-tensor into individual
      contributions revealed that, despite the large ZFS, the observed significant
      anisotropy should be largely attributed to spin-dipolar contributions. The
      analysis of both, metal and ligand A-tensors, is consistent with a highly
      covalent character of the Co-S bonds.

PMID- 21848260
TI  - Ca10Ge16B6O51 and Cd12Ge17B8O58: two types of new 3D frameworks based on BO4
      tetrahedra and 1D [Ge4O12]n chains.
AB  - Two new acentric borogermanates, Ca(10)Ge(16)B(6)O(51) (Pba2) and
      Cd(12)Ge(17)B(8)O(58) (P4), have been successfully synthesized by high
      temperature solid-state reactions of CaCO(3) (or CdCO(3)), GeO(2), and H(3)BO(3).
      Both structures display the same one-dimensional (1D) [Ge(4)O(12)](n) chains
      composed of GeO(4) tetrahedra and GeO(6) octahedra. In Ca(10)Ge(16)B(6)O(51),
      neighboring 1D [Ge(4)O(12)](n) chains are condensed into a two-dimensional (2D)
      [Ge(4)O(10.75)](n) layer via corner sharing, and such layers are further
      interconnected by "isolated" BO(4) tetrahedra and B(2)O(7) dimers into a three
      dimensional (3D) framework, forming 1D tunnels of 5-, 6-, and 7-MRs along the c
      axis that are occupied by Ca(2+) cations. In Cd(12)Ge(17)B(8)O(58), neighboring
      1D [Ge(4)O(12)](n) chains are interconnected into a [Ge(4)O(10.5)](n) open
      framework via corner sharing with large pores filled by big [Ge(B(2)O(7))(4)](28
      ) clusters, leading to formation of three types of 1D tunnels of 5-, 6-, and 7
      membered rings (MRs) along the c axis which are occupied by the Cd(2+) cations.
      Both compounds are transparent in the range of 0.3-6.67 MUm and exhibit very weak
      SHG responses.

PMID- 21848259
TI  - Bioinspired systems for metal-ion sensing: new emissive peptide probes based on
      benzo[d]oxazole derivatives and their gold and silica nanoparticles.
AB  - Seven new bioinspired chemosensors (2-4 and 7-10) based on fluorescent peptides
      were synthesized and characterized by elemental analysis, (1)H and (13)C NMR,
      melting point, matrix-assisted laser desorption-ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS), and IR and UV-vis absorption and emission
      spectroscopy. The interaction with transition- and post-transition-metal ions
      (Cu(2+), Ni(2+), Ag(+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Fe(3+)) has been
      explored by absorption and fluorescence emission spectroscopy and MALDI-TOF-MS.
      The reported fluorescent peptide systems, introducing biological molecules in the
      skeleton of the probes, enhance their sensitivity and confer them strong
      potential for applications in biological fields. Gold and silica nanoparticles
      functionalized with these peptides were also obtained. All nanoparticles were
      characterized by dynamic light scattering, transmission electron microscopy, and
      UV-vis absorption and fluorescence spectroscopy. Stable gold nanoparticles
      (diameter 2-10 nm) bearing ligands 1 and 4 were obtained by common reductive
      synthesis. Commercial silica nanoparticles were decorated at their surface using
      compounds 8-10, linked through a silane spacer. The same chemosensors were also
      taken into aqueous solutions through their dispersion in the outer layer of
      silica core/poly(ethylene glycol) shell nanoparticles. In both cases, these
      complex nanoarchitectures behaved as new sensitive materials for Ag(+) and Hg(2+)
      in water. The possibility of using these species in this solvent is particularly
      valuable because the impact on human health of heavy- and transition-metal-ion
      pollution is very severe, and all analytical and diagnostics investigations
      involve a water environment.

PMID- 21848261
TI  - Boron complexes of pyrrolyl ligands.
AB  - Complexes of boron with ligands containing pyrrolyl motifs are surveyed. The
      ligands range from simple pyrrolyl groups to dipyrroles and linear terpyrroles.
      Macrocyclic ligands include tripyrroles, which encompass subphthalocyanines,
      subporphyrins, subtriazaporphyrins, and subtribenzoporphyins, the familiar
      tetrapyrroles porphyrin and corrole but also N-confused and -fused porphyrins,
      and expanded porphyrins containing up to eight pyrroles. The role of boron in
      these compounds depends on the nature of the ligand. Boron acts as a Lewis acid
      center in simple boron pyrrolyl compounds, and as a structure-directing and
      templating agent in the cyclic terpyrroles and some of the expanded porphyrins.
      The difluorboron dipyrrins are well-known as fluorescent dyes. Boron porphyrins
      and corroles are unusual in containing two coordinated boron atoms rather than
      the single coordinated atom usually occurring in these ligands, and the proximity
      of two boron atoms at close quarters in the ligand cavities gives rise to some
      unusual reaction and redox chemistry. The survey is organized by the number of
      pyrrole moieties occurring in the ligand and focuses on new and unique chemistry
      observed for the complexes.

PMID- 21848262
TI  - Simulation of an electrical double layer model with a low dielectric layer
      between the electrode and the electrolyte.
AB  - We report Monte Carlo simulation results for double layers of 1:1 and 2:1
      electrolytes near an electrode with an inner layer that has a dielectric
      constant, epsilon(2), smaller than that of the electrolyte, epsilon(3). The
      electrolyte is modeled in the implicit solvent framework (primitive model), while
      the electrode is a metal electrode in this study (epsilon(1) -> infinity). The
      charged hard sphere ions are not allowed to enter into the inner layer. We show
      that the capacitance of the inner layer is C(delta) = epsilon(0)(epsilon(2) +
      epsilon(3))/2delta, where delta is the thickness of the inner layer. This result
      is different from that obtained from solutions of the Poisson-Boltzmann equation
      (epsilon(0)epsilon(2)/delta), indicating that interpretation of experimental data
      with a fitted epsilon(2) dielectric constant of the inner layer must be done
      using a different equation. We also show that the properties of the diffuse layer
      are not independent of the value of epsilon(2), which is a usual assumption of
      the Poisson-Boltzmann theory. This is mainly because the repulsive image charges
      repel both the counterions and the co-ions, while the electrode charge attracts
      the counterions and repels the co-ions.

PMID- 21848263
TI  - Interface of covalently bonded phospholipids with a phosphorylcholine head:
      characterization, protein nonadsorption, and further functionalization.
AB  - Surface anchored poly(methylhydrosiloxane) (PMHS) thin films on oxidized silicon
      wafers or glass substrates were functionalized via the SiH hydrosilylation
      reaction with the internal double bonds of 1,2-dilinoleoyl-sn-glycero-3
      phosphorylcholine (18:2 Cis). The surface was characterized by X-ray
      photoelectron spectroscopy, contact angle measurements, atomic force microscopy,
      and scanning electron microscopy. These studies showed that the PMHS top layer
      could be efficiently modified resulting in an interfacial high density of
      phospholipids. Grafted phospholipids made the initially hydrophobic surface
      (theta = 106 degrees ) very hydrophilic and repellent toward avidin, bovine serum
      albumin, bovine fibrinogen, lysozyme, and alpha-chymotrypsin adsorption in
      phosphate saline buffer pH 7.4. The surface may constitute a new background
      stable support with increased biocompatibility. Further possibilities of
      functionalization on the surface remain available owing to the formation of
      interfacial SiOH groups by Karstedt-catalyzed side reactions of SiH groups with
      water. The presence of interfacial SiOH groups was shown by zeta potential
      measurements. The reactivity and surface density of SiOH groups were checked by
      fluorescence after reaction of a monoethoxy silane coupling agent bearing Alexa
      as fluorescent probe.

PMID- 21848264
TI  - Enantioselective alpha-arylation of N-acyloxazolidinones with copper(II)
      bisoxazoline catalysts and diaryliodonium salts.
AB  - A new strategy for the catalytic enantioselective alpha-arylation of N
      acyloxazolidinones with chiral copper(II)-bisoxazoline complexes and
      diaryliodonium salts is described. The mild catalytic conditions are
      operationally simple, produce valuable synthetic building blocks in excellent
      yields and enantioselectivities, and can be applied to the synthesis of important
      nonsteroidal anti-inflammatory agents and their analogues.

PMID- 21848265
TI  - Enantioselective alpha-arylation of carbonyls via Cu(I)-bisoxazoline catalysis.
AB  - The enantioselective alpha-arylation of both lactones and acyl oxazolidones has
      been accomplished using a combination of diaryliodonium salts and copper
      catalysis. These mild catalytic conditions provide a new strategy for the
      enantioselective construction and retention of enolizable alpha-carbonyl benzylic
      stereocenters, a valuable synthon for the production of medicinal agents.

PMID- 21848266
TI  - Anti-inflammatory principles from Cordyceps sinensis.
AB  - In order to explore the anti-inflammatory principles of the mycelia of Cordyceps
      sinensis, the crude extract and partially purified fractions were examined for
      their inhibition of superoxide anion generation and elastase release. Further
      chemical investigation of the bioactive fractions has resulted in the
      identification of 50 compounds, including five constituents, cordysinins A-E (1
      5), reported from a natural source for the first time. In addition, compounds
      were examined for their anti-inflammatory activity. 1-(5-Hydroxymethyl-2-furyl)
      beta-carboline displayed the most significant inhibition of superoxide anion
      generation and elastase release with IC50 values of 0.45+/-0.15 and 1.68+/-0.32
      MUM, respectively.

PMID- 21848268
TI  - Monanchocidins B-E: polycyclic guanidine alkaloids with potent antileukemic
      activities from the sponge Monanchora pulchra.
AB  - New unusual polycyclic guanidine alkaloids monanchocidins B-E (2-5) along with
      monanchocidin A (1), which we recently described, were isolated from the Far
      Eastern marine sponge Monanchora pulchra. Their structures were established using
      spectroscopic data and chemical transformations. Compounds 1-5 show potent
      cytotoxic activities against HL-60 human leukemia cells with IC50 values of 540,
      200, 110, 830, and 650 nM, respectively.

PMID- 21848269
TI  - A foldamer-based chiroptical molecular switch that displays complete inversion of
      the helical sense upon anion binding.
AB  - Chiral indolocarbazole dimers fold into a helical conformation by virtue of
      intramolecular hydrogen bonds, as demonstrated by (1)H NMR and CD spectra and
      optical rotations. In particular, the optical properties of the dimers were found
      to be extremely sensitive to the nature of the solvent, depending on whether they
      are folded or not. The helical sense of the dimers can be reversibly switched by
      binding sulfate ion, which gives rise to complete inversion of the CD spectra.
      The binding mode and absolute stereochemistry of the sulfate complexes was
      unequivocally determined by single-crystal X-ray structures, which are all
      consistent with the CD and (1)H NMR spectra in solution.

PMID- 21848270
TI  - Shape matters: plasmonic nanoparticle shape enhances interaction with dielectric
      substrate.
AB  - Numerical analyses of the ultraviolet and visible plasmonic spectra measured from
      hemispherical gallium nanostructures on dielectric substrates reveal that
      resonance frequencies are quite sensitive to illumination angle and polarization
      in a way that depends on nanostructure size, shape, and substrate. Large,
      polarization-dependent splittings arise from the broken symmetry of hemispherical
      gallium nanoparticles on sapphire substrates, inducing strong interactions with
      the substrate that depend sensitively on the angle of illumination and the
      nanoparticle diameter.

PMID- 21848271
TI  - LaAlO3 hollow spheres: synthesis and luminescence properties.
AB  - Nearly monodisperse LaAlO(3) hollow spheres are synthesized by a novel precursor
      thermal decomposition method. Spherical colloids of capsulelike precursors with
      uniform diameters of 273 +/- 35 nm have been synthesized by a solvothermal
      method. These spherical colloids could convert to LaAlO(3) hollow spheres with
      diameters of 166 +/- 26 nm by a thermal decomposition process. The thermal
      transformation process from the precursors to LaAlO(3) was characterized by
      thermogravimetric analysis (TGA), X-ray diffraction (XRD), and the Fourier
      transform infrared spectroscopy (FT-IR). By the doping of various lanthanide ions
      (Sm(3+), Eu(3+), and Tb(3+)), the emission luminescence of lanthanide-doped
      LaAlO(3) hollow microspheres can be tuned from red to green. In particular, these
      luminescent LaAlO(3) hollow spheres can be well dispersed in polar solvents such
      as the ethanol and water, which broadens the range of potential applications of
      these hollow spheres. The UV-vis absorption spectra show energy absorption at
      211, 223, and 313 nm corresponding to the host lattice absorption and charge
      transfer transitions. The results are in good agreement with the peaks observed
      in the excitation spectra.

PMID- 21848272
TI  - Assessing model uncertainty of bioaccumulation models by combining chemical space
      visualization with a process-based diagnostic approach.
AB  - As models describing human exposure to organic chemicals gain wider use in
      chemical risk assessment and management, it becomes important to understand their
      uncertainty. Although evaluation of parameter sensitivity/uncertainty is
      increasingly common, model uncertainty is rarely assessed. When it is, the
      assessment is generally limited to a handful of chemicals. In this study, a
      strategy for more comprehensive model uncertainty assessment was developed. A
      regulatory model (EUSES) was compared with a research model based on more recent
      science. Predicted human intake was used as the model end point. Chemical space
      visualization techniques showed that the extent of disagreement between the
      models varied strongly with chemical partitioning properties. For each region of
      disagreement, the primary human exposure vector was determined. The differences
      between the models' process algorithms describing these exposure vectors were
      identified and evaluated. The equilibrium assumption for root crops in EUSES
      caused overestimations in daily intake of superhydrophobic chemicals (log K(OW) >
      11, log K(OA) > 10), whereas EUSES's approach to calculating bioaccumulation in
      fish prey resulted in underestimations for hydrophobic compounds (log K(OW) ~ 6
      8). Uptake of hydrophilic chemicals from soil and bioaccumulation of
      superhydrophobic chemicals in zooplankton were identified as important research
      areas to enable further reduction of model uncertainty in bioaccumulation models.

PMID- 21848273
TI  - Optimization and evaluation of a sheathless capillary electrophoresis
      electrospray ionization mass spectrometry platform for peptide analysis:
      comparison to liquid chromatography-electrospray ionization mass spectrometry.
AB  - In this study we have evaluated the suitability of a sheathless capillary
      electrophoresis-electrospray ionization mass spectrometry (CE-ESI-MS) interface
      with a porous tip as the nanospray emitter for use in peptide analysis. A
      positively charged capillary coating and 0.1% formic acid as background
      electrolyte were used for separation upstream from mass spectrometry
      characterization. The influence of the distance between emitter tip and MS inlet,
      ESI voltage applied, and of the electroosmotic flow (EOF) on electrospray
      performance and efficiency of the system was investigated in detail. Under
      optimized conditions, less than 30 amol of a model peptide (angiotensin I) was
      required for a detection in the base peak electropherogram and positive
      identification via tandem MS. Three different cationic capillary coatings were
      investigated for stability, resolution, and EOF and were found to enable
      reproducible separations by CE-ESI-MS. After optimizing MS settings, the
      effectiveness of the CE-ESI-MS method developed was compared with a state-of-the
      art nano-liquid chromatography (LC)-ESI-MS method by analyzing Arg-C-digested rat
      testis linker histones with both systems. With comparable amounts of sample
      applied, the number of identified peptides increased by more than 60% when using
      CE-ESI-MS. We found that low molecular mass peptides (below 1400 Da) were
      preferentially identified by CE-ESI-MS, since this group of peptides poorly
      interacted with the reversed-phase material in the nano-LC system. Finally, total
      analysis time in LC-ESI-MS for three runs including equilibration was nearly 4
      times longer than that of CE-ESI-MS: 246 versus 66 min.

PMID- 21848274
TI  - Multifunctional mesoporous silica nanocomposite nanoparticles for theranostic
      applications.
AB  - Clever combinations of different types of functional nanostructured materials
      will enable the development of multifunctional nanomedical platforms for
      multimodal imaging or simultaneous diagnosis and therapy. Mesoporous silica
      nanoparticles (MSNs) possess unique structural features such as their large
      surface areas, tunable nanometer-scale pore sizes, and well-defined surface
      properties. Therefore, they are ideal platforms for constructing multifunctional
      materials that incorporate a variety of functional nanostructured materials.  In
      this Account, we discuss recent progress by our group and other researchers in
      the design and fabrication of multifunctional nanocomposite nanoparticles based
      on mesoporous silica nanostructures for applications to simultaneous diagnosis
      and therapy. Versatile mesoporous silica-based nanocomposite nanoparticles were
      fabricated using various methods. Here, we highlight two synthetic approaches:
      the encapsulation of functional nanoparticles within a mesoporous silica shell
      and the assembly of nanoparticles on the surface of silica nanostructures.
      Various nanoparticles were encapsulated in MSNs using surfactants as both phase
      transfer agents and pore-generating templates. Using MSNs as a scaffold,
      functional components such as magnetic nanoparticles and fluorescent dyes have
      been integrated within these systems to generate multifunctional nanocomposite
      systems that maintain their individual functional characteristics. For example,
      uniform mesoporous dye-doped silica nanoparticles immobilized with multiple
      magnetite nanocrystals on their surfaces have been fabricated for their use as a
      vehicle capable of simultaneous magnetic resonance (MR) and fluorescence imaging
      and drug delivery. The resulting nanoparticle-incorporated MSNs were then tested
      in mice with tumors. These in vivo experiments revealed that these
      multifunctional nanocomposite nanoparticles were delivered to the tumor sites via
      passive targeting. These nanocomposite nanoparticles served as successful
      multimodal imaging probes and also delivered anticancer drugs to the tumor site.
      With innumerable combinations of imaging modalities and drug delivery available
      within these vehicles, multifunctional nanocomposite nanoparticles provide new
      opportunities for clinical diagnostics and therapeutics.

PMID- 21848275
TI  - The diarylprolinol silyl ether system: a general organocatalyst.
AB  - The past few decades have witnessed some of the most important and
      revolutionizing advances in the field of asymmetric catalysis. Chemists no longer
      rely solely on natural sources as the starting point of their synthetic strategy,
      as in chiral pool or auxiliary-based synthesis. Instead, naturally occurring
      chiral motifs are selected and, either unchanged or after modification, used in
      substoichiometric amounts as chiral catalysts or ligands. In this way, they
      effectively transfer their chirality to prochiral substrates, thereby rapidly
      amplifying and diversifying the arsenal of useful chiral building blocks
      available to the synthetic community. A long-standing goal in the pursuit of new
      catalytic systems is the discovery of general catalysts. Ideally, such catalytic
      systems should be capable of promoting a large number of enantioselective
      reactions, via multiple modes of activation, with good substrate tolerance and
      high stereoselectivity. In this Account, we describe the synthetic usefulness,
      efficiency, selectivity, and robustness of the diarylprolinol silyl ether system
      as the catalyst in various reactions of aldehydes. Based on the diarylprolinol
      silyl ether system, several studies on enamine-mediated transformations of
      saturated aldehydes have resulted in the introduction of different
      functionalities into the alpha-position of aldehydes in a highly stereoselective
      manner. This HOMO-activation concept was later extended to include alpha,beta
      unsaturated aldehydes, which after condensation with the aminocatalyst generate a
      dienamine species capable of undergoing stereoselective Diels-Alder-type
      reactions. As a result, the effective functionalization of the gamma-position of
      the aldehyde is achieved. Recently, the activation principle was further
      developed to include 2,4-dienals, which form trienamine intermediates upon
      condensation with the aminocatalyst. The trienamines effectively react with
      carbon-centered dienophiles, forming aldehyde products having up to four
      contiguous stereocenters. Because of the concerted nature of the reaction and the
      efficient catalyst shielding of the beta-position, the stereoinduction is
      achieved at the remote epsilon-position of the original aldehyde. Complementary
      to the enamine-mediated activations, alpha,beta-unsaturated aldehydes can also be
      efficiently functionalized by applying the diarylprolinol silyl ether system via
      conjugate addition through iminium-ion-mediated processes, that is, LUMO
      activation. In such reactions, the aminocatalyst not only effectively shields one
      of the enantiotopic faces of the enal, it also ensures excellent
      chemoselectivity, affording 1,4-adducts as the only products. Several different
      carbon and heteroatom nucleophiles can be added in a highly stereoselective
      fashion. The ability of the catalysts to participate in various enamine- and
      iminium-ion-mediated processes also makes them ideal for the sequential addition
      of nucleophiles and electrophiles in a cascade manner. These cascade reactions
      thereby afford access to products having at least two stereocenters. In the years
      to come, the diarylprolinol silyl ether catalysts will probably maintain their
      prominent position as general catalysts in the field of aminocatalysis. Moreover,
      recent efforts devoted to mechanistic studies might soon engender further
      advances with this versatile catalytic system, particularly in the areas of
      activation modes, catalyst loadings, and industrial applications.

PMID- 21848276
TI  - High-throughput screening of one-bead-one-compound libraries: identification of
      cyclic peptidyl inhibitors against calcineurin/NFAT interaction.
AB  - One-bead-one-compound (OBOC) libraries provide a powerful tool for drug discovery
      as well as biomedical research. However, screening a large number of
      beads/compounds (>1 million) and rank ordering the initial hits (which are
      covalently attached to a solid support) according to their potencies still post
      significant technical challenges. In this work, we have integrated some of the
      latest technical advances from our own as well as other laboratories to develop a
      general methodology for rapidly screening large OBOC libraries. The methodology
      has been applied to synthesize and screen a cyclic peptide library that features:
      (1) spatially segregated beads containing cyclic peptides on the surface layer
      and linear encoding peptides in their interior; (2) rapid on-bead screening of
      the library (>1 million) by a multistage procedure (magnetic bead sorting, enzyme
      linked assay, and fluorescence based screening); (3) selective release of cyclic
      peptides from single positive beads for solution-phase determination of their
      binding affinities; and (4) hit identification by partial Edman degradation/mass
      spectrometry (PED/MS). Screening of the library against protein phosphatase
      calcineurin (Cn) identified a series of cyclic peptides that bind to the
      substrate-docking site for nuclear factor of activated T cells (NFAT) with K(D)
      values of ~1 MUM. Further improvement of the affinity and specificity of these
      compounds may lead to a new class of immunosuppressive agents that are more
      selective and therefore less toxic than cyclosporine A and FK506.

PMID- 21848278
TI  - Kinetic modeling of ethane pyrolysis at high conversion.
AB  - The primary objective of this study is to develop an improved first-principle
      based mechanism that describes the molecular weight growth kinetics observed
      during ethane pyrolysis. A proper characterization of the kinetics of ethane
      pyrolysis is a prerequisite for any analysis of hydrocarbon pyrolysis and
      oxidation. Flow reactor experiments were performed with ~50/50 ethane/nitrogen
      mixtures with temperatures ranging from 550 to 850  degrees C at an absolute
      pressure of ~0.8 atm and a residence time of ~5 s. These conditions result in
      ethane conversions ranging from virtually no reaction to ~90%. Comparisons of
      predictions using our original mechanism to these data yielded very satisfactory
      results in terms of the temperature dependence of ethane conversion and
      prediction of the major products ethylene and hydrogen. However, there were
      discrepancies in some of the minor species concentrations that are involved in
      the molecular weight growth kinetics. We performed a series of CBS-QB3 analyses
      for the C(3)H(7), C(4)H(7), and C(4)H(9) potential energy surfaces to better
      characterize the radical addition reactions that lead to molecular weight growth.
      We also extended a published C(6)H(9) PES to include addition of vinyl to
      butadiene. The results were then used to calculate pressure-dependent rate
      constants for the multiple reaction pathways of these addition reactions.
      Inclusion of the unadjusted rate constants resulting from these analyses in the
      mechanism significantly improved the description of several of the species
      involved in molecular weight growth kinetics. We compare the predictions of this
      improved model to those obtained with a consensus model recently published as
      well as to ethane steam cracking data. We find that a particularly important
      reaction is that of vinyl addition to butadiene. Another important observation is
      that several radical addition reactions are partially equilibrated. Not only does
      this mean that reliable thermodynamic parameters are essential for an accurate
      model, but also that the reaction set describing molecular weight growth
      chemistry must include a final product that is sufficiently stable to shift the
      equilibrium toward this product despite the decrease in entropy that accompanies
      molecular weight growth. Another reaction, H addition to olefins, was found to
      inhibit molecular weight growth by leading to the production of a lower olefin
      plus methyl radicals.

PMID- 21848277
TI  - Cancer theranostics with near-infrared light-activatable multimodal
      nanoparticles.
AB  - Nanomaterials that interact with light provide a unique opportunity for
      applications in biophotonic nanomedicine. Image-guided therapies could be
      designed based on multifunctional nanoparticles (NPs). Such NPs have a strong and
      tunable surface plasmon resonance absorption in the near-infrared region and can
      be detected using multiple imaging modalities (magnetic resonance imaging,
      nuclear imaging, and photoacoustic imaging). These novel nanostructures, once
      introduced, are expected to home in on solid tumors either via a passive
      targeting mechanism (i.e., the enhanced permeability and retention effect) or via
      an active targeting mechanism facilitated by ligands bound to their surfaces.
      Once the NPs reach their target tissue, their activity can then be turned on
      using an external stimulus. For example, photothermal conducting NPs primarily
      act by converting light energy into heat. As a result, the temperature in the
      treatment volume is elevated above the thermal damage threshold, which kills the
      cells. This process, termed photothermal ablation therapy (PTA), is effective,
      but it is also unlikely to kill all tumor cells when used alone. In addition to
      PTA, photothermal conducting NPs can also efficiently trigger the release of
      drugs and activate RNA interference. A multimodal approach, which permits
      simultaneous PTA therapy, chemotherapy, and therapeutic RNA interference, has the
      potential to completely eradicate residual diseased cells.  In this Account, we
      provide an up-to-date review of the synthesis and characterization,
      functionalization, and in vitro and in vivo evaluation of NIR lightactivatable
      multifunctional nanostructures used for imaging and therapy. We emphasize
      research on hollow gold nanospheres, magnetic core-shell gold nanoshells, and
      semiconductor copper monosulfide NPs. We discuss three types of novel drug
      delivery systems in which hollow gold nanospheres are used to mediate controlled
      drug release.

PMID- 21848279
TI  - Selection of in silico drug screening results for G-protein-coupled receptors by
      using universal active probes.
AB  - We developed a new protocol for in silico drug screening for G-protein-coupled
      receptors (GPCRs) using a set of "universal active probes" (UAPs) with an
      ensemble docking procedure. UAPs are drug-like compounds, which are actual active
      compounds of a variety of known proteins. The current targets were nine human
      GPCRs whose three-dimensional (3D) structures are unknown, plus three GPCRs,
      namely beta(2)-adrenergic receptor (ADRB2), A(2A) adenosine receptor (A(2A)), and
      dopamine D3 receptor (D(3)), whose 3D structures are known. Homology-based models
      of the GPCRs were constructed based on the crystal structures with careful
      sequence inspection. After subsequent molecular dynamics (MD) simulation taking
      into account the explicit lipid membrane molecules with periodic boundary
      conditions, we obtained multiple model structures of the GPCRs. For each target
      structure, docking-screening calculations were carried out via the ensemble
      docking procedure, using both true active compounds of the target proteins and
      the UAPs with the multiple target screening (MTS) method. Consequently, the
      multiple model structures showed various screening results with both poor and
      high hit ratios, the latter of which could be identified as promising for use in
      in silico screening to find candidate compounds to interact with the proteins. We
      found that the hit ratio of true active compounds showed a positive correlation
      to that of the UAPs. Thus, we could retrieve appropriate target structures from
      the GPCR models by applying the UAPs, even if no active compound is known for the
      GPCRs. Namely, the screening result that showed a high hit ratio for the UAPs
      could be used to identify actual hit compounds for the target GPCRs.

PMID- 21848280
TI  - Method for the direct observation and quantification of survival of bacteria
      attached to negatively or positively charged surfaces in an aqueous medium.
AB  - The risk of groundwater contamination by microbial pathogens is linked to their
      survival in the subsurface. Although there is a large body of literature on the
      inactivation behavior of suspended (planktonic) microorganisms, little is known
      about the inactivation of bacteria when attached to sand grain surfaces in
      groundwater aquifers. The main goal of this study was to develop a fluorescence
      based experimental technique for evaluating the extent of inactivation over time
      of bacteria adhered onto a surface in an aqueous environment. Key features of the
      developed technique are as follows: (i) attached cells do not need to be removed
      from the surface of interest for quantification, (ii) bacterial inactivation can
      be examined in real-time for prolonged time periods, and (iii) the system remains
      undisturbed (i.e., the aqueous environment is unchanged) during the assay. A
      negatively or positively charged substrate (i.e., bare or coated glass slide) was
      mounted in a parallel-plate flow cell, bacteria were allowed to attach onto the
      substrate, and the loss of bacterial membrane integrity and respiratory activity
      were investigated as a function of time by fluorescence microscopy using
      Live/Dead BacLight and BacLight RedoxSensor CTC (5-cyano-2,3-ditolyl tetrazolium
      chloride) viability assays. These two different measures of bacterial
      inactivation result in comparable trends in bacterial inactivation, confirming
      the validity of the experimental technique. The results of this work show that
      the developed technique is sensitive enough to distinguish between the
      inactivation kinetics of different representative bacteria attached to either a
      negatively charged (bare glass) surface or a positively charged (coated glass)
      surface. Hence, the technique can be used to characterize bacterial inactivation
      kinetics when attached to environmentally relevant surfaces over a broad range of
      groundwater chemistries.

PMID- 21848281
TI  - Efficient enumeration of stereoisomers of outerplanar chemical graphs using
      dynamic programming.
AB  - Exhaustive and nonredundant generation of stereoisomers of a chemical compound
      with a specified constitution is an important tool for molecular structure
      elucidation and molecular design. It is known that many chemical compounds have
      outerplanar graph structures. In this paper we deal with chemical compounds
      composed of carbon, hydrogen, oxygen, and nitrogen atoms whose graphical
      structures are outerplanar and consider stereoisomers caused only by asymmetry
      around carbon atoms. Based on dynamic programming, we propose an algorithm of
      generating all stereoisomers without duplication. We treat a given outerplanar
      graph as a graph rooted at its structural center. Our algorithm first recursively
      computes the number of stereoisomers of the subgraph induced by the descendants
      of each vertex and then constructs each stereoisomer by backtracking the process
      of computing the numbers of stereoisomers. Our algorithm correctly counts the
      number of stereoisomers in O(n) time and space and correctly enumerates all of
      the stereoisomers in O(n3) time per stereoisomer on average and in O(n) space,
      where n is the number of atoms in a given structure.

PMID- 21848282
TI  - The induced magnetic field.
AB  - Aromaticity is indispensable for explaining a variety of chemical behaviors,
      including reactivity, structural features, relative energetic stabilities, and
      spectroscopic properties. When interpreted as the spatial delocalization of pi
      electrons, it represents the driving force for the stabilization of many planar
      molecular structures. A delocalized electron system is sensitive to an external
      magnetic field; it responds with an induced magnetic field having a particularly
      long range. The shape of the induced magnetic field reflects the size and
      strength of the system of delocalized electrons and can have a large influence on
      neighboring molecules.  In 2004, we proposed using the induced magnetic field as
      a means of estimating the degree of electron delocalization and aromaticity in
      planar as well as in nonplanar molecules. We have since tested the method on
      aromatic, antiaromatic, and nonaromatic compounds, and a refinement now allows
      the individual treatment of core-, sigma-, and pi-electrons.  In this Account, we
      describe the use of the induced magnetic field as an analytical probe for
      electron delocalization and its application to a large series of uncommon
      molecules. The compounds include borazine; all-metal aromatic systems Al(4)(n-);
      molecular stars Si(5)Li(n)(6-n); electronically stabilized planar tetracoordinate
      carbon; planar hypercoordinate atoms inside boron wheels; and planar boron wheels
      with fluxional internal boron cluster moieties. In all cases, we have observed
      that planar structures show a high degree of electron delocalization in the pi
      electrons and, in some examples, also in the sigma-framework.  Quantitatively,
      the induced magnetic field has contributions from the entire electronic system of
      a molecule, but at long range the contributions arising from the delocalized
      electronic pi-system dominate. The induced magnetic field can only indirectly be
      confirmed by experiment, for example, through intermolecular contributions to NMR
      chemical shifts. We show that calculating the induced field is a useful method
      for understanding any planar organic or inorganic system, as it corresponds to
      the intuitive Pople model for explaining the anomalous proton chemical shifts in
      aromatic molecules. Indeed, aromatic, antiaromatic, and nonaromatic molecules
      show differing responses to an external field; that is, they reduce, augment, or
      do not affect the external field at long range. The induced field can be
      dissected into different orbital contributions, in the same way that the nucleus
      independent chemical shift or the shielding function can be separated into
      component contributions. The result is a versatile tool that is particularly
      useful in the analysis of planar, densely packed systems with strong orbital
      contributions directly atop individual atoms.

PMID- 21848283
TI  - Electrical transport properties of oligothiophene-based molecular films studied
      by current sensing atomic force microscopy.
AB  - Using conducting probe atomic force microscopy (CAFM) we have investigated the
      electrical conduction properties of monolayer films of a pentathiophene
      derivative on a SiO(2)/Si-p+ substrate. By a combination of current-voltage
      spectroscopy and current imaging we show that lateral charge transport takes
      place in the plane of the monolayer via hole injection into the highest occupied
      molecular orbitals of the pentathiophene unit. Our CAFM data suggest that the
      conductivity is anisotropic relative to the crystalline directions of the
      molecular lattice.

PMID- 21848284
TI  - Development of a minimal kinase ensemble receptor (MKER) for surrogate AutoShim.
AB  - The target-tailored 3-D virtual screening (VS) method "Surrogate AutoShim" adds
      pharmacophoric shims to a 16-kinase crystal structure "Universal Kinase Ensemble
      Receptor" (UKER) to generate highly predictive, target-customized docking models.
      Predocking a corporate archive of millions of compounds into the 16-structure
      ensemble takes months. However, since the 16 UKER structures are always the same,
      docking need only be done once. The predocked results are then "shimmed" to
      reproduce experimental training data for any number of additional kinases far
      more accurately than conventional docking. Training new kinase models and
      predicting activity for millions of predocked compounds against dozens of kinases
      takes only hours. However reducing the predocking time would make the method even
      more advantageous. Sequential Floating Forward Search (SFFS) was employed to
      rationally identify a reduced subset using only 8 of the 16 structures, a
      "Minimal Kinase Ensemble Receptor" (MKER) that preserved the predictive accuracy
      for 20 kinase models. Furthermore, a performance evaluation of this subset on an
      extended set of 52 kinase targets and 100,000 compounds showed statistical model
      performance comparable to the original UKER. The MKER has halved the time for
      predocking large databases of internal and commercial compounds. For ad hoc
      virtual libraries, where predocking is not possible, 2- or 3-kinases "Approximate
      Kinase Ensemble Receptors" (AKER) were also identified with only a modest loss of
      prediction accuracy.

PMID- 21848285
TI  - Performance evaluation using a three compartment mass balance for the removal of
      volatile organic compounds in pilot scale constructed wetlands.
AB  - To perform a general assessment of treatment efficiency, a mass balance study was
      undertaken for two types of constructed wetlands (CWs), planted gravel filters
      and plant root mat systems, for treating VOC (benzene; MTBE) polluted groundwater
      under field conditions. Contaminant fate was investigated in the respective
      water, plant, and atmosphere compartments by determining water and atmospheric
      contaminant loads and calculating contaminant plant uptake, thereby allowing for
      an extended efficiency assessment of CWs. Highest total VOC removal was achieved
      during summer, being pronounced for benzene compared to MTBE. According to the
      experimental results and the calculations generated by the balancing model,
      degradation in the rhizosphere and plant uptake accounted for the main benzene
      removal processes, of 76% and 13% for the gravel bed CW and 83% and 11% for the
      root mat system. Volatilization flux of benzene and MTBE was low (<5%) for the
      gravel bed CW, while in the root mat system direct contact of aqueous and gaseous
      phases favored total MTBE volatilization (24%). With this applied approach, we
      present detailed contaminant mass balances that allow for conclusive quantitative
      estimation of contaminant elimination and distribution processes (e.g., total,
      surface, and phytovolatilization, plant uptake, rhizodegradation) in CWs under
      field conditions.

PMID- 21848286
TI  - Energetic preference of 8-oxoG eversion pathways in a DNA glycosylase.
AB  - Base eversion is a fundamental process in the biochemistry of nucleic acids,
      allowing proteins engaged in DNA repair and epigenetic modifications to access
      target bases in DNA. Crystal structures reveal end points of these processes, but
      not the pathways involved in the dynamic process of base recognition. To
      elucidate the pathway taken by 8-oxoguanine during base excision repair by Fpg,
      we calculated free energy surfaces during eversion of the damaged base through
      the major and minor grooves. The minor groove pathway and free energy barrier (6
      7 kcal/mol) are consistent with previously reported results (Qi, Y.; Spong, M.
      C.; Nam, K.; Banerjee, A.; Jiralerspong, S.; Karplus, M.; Verdine, G. L. Nature
      2009, 462, 762.) However, eversion of 8-oxoG through the major groove encounters
      a significantly lower barrier (3-4 kcal/mol) more consistent with experimentally
      determined rates of enzymatic sliding during lesion search (Blainey, P. C.; van
      Oijent, A. M.; Banerjee, A.; Verdine, G. L.; Xie, X. S. Proc. Natl. Acad. Sci.
      U.S.A. 2006, 103, 5752.). Major groove eversion has been suggested for other
      glycosylases, suggesting that in addition to function, dynamics of base eversion
      may also be conserved.

PMID- 21848288
TI  - Polyamorphic amorphous silicon at high pressure: raman and spatially resolved X
      ray scattering and molecular dynamics studies.
AB  - We studied the low-frequency Raman and X-ray scattering behavior of amorphous
      silicon (a-Si) at high pressure throughout the range where the density-driven
      polyamorphic transformation between the low-density amorphous (LDA) semiconductor
      and a novel metallic high-density amorphous (HDA) polyamorph occurs. The
      experimental data were analyzed with the aid of molecular dynamics (MD)
      simulations using the Stillinger-Weber potential. The heat capacity of a-Si
      obtained from the low pressure Raman data exhibits non Debye-like behavior, but
      the effect is small, and our data support the conclusion that no boson peak is
      present. The high-pressure Raman data show the presence of a distinct low
      frequency band for the HDA polyamorph in agreement with ab initio MD simulations.
      Spatially resolved synchrotron X-ray diffraction was used to study the high
      pressure behavior of the a-Si sample throughout the LDA-HDA transition range
      without interference by crystallization events. The X-ray data were analyzed
      using an iterative refinement strategy to extract real-space structural
      information. The appearance of the first diffraction peak (FDP) in the scattering
      function S(Q) is discussed in terms of the void structure determined from Voronoi
      analysis of the MD simulation data.

PMID- 21848287
TI  - Mass spectrometry-based protein footprinting characterizes the structures of
      oligomeric apolipoprotein E2, E3, and E4.
AB  - The three common isoforms of apolipoprotein E (ApoE) differ at two sites in their
      299 amino acid sequence; these differences modulate the structure of ApoE to
      affect profoundly the isoform associations with disease. The epsilon4 allele in
      particular is strongly associated with Alzheimer's disease. The study of the
      structural effects of these mutation sites in aqueous media is hampered by the
      aggregation proclivity of each ApoE isoform. Hence, understanding the differences
      between isoforms has thus far relied on lower resolution biophysical
      measurements, mutagenesis, homology studies, and the use of truncated ApoE
      variants. In this study, we report two comparative studies of the ApoE family by
      using the mass spectrometry-based protein footprinting methods of FPOP and
      glycine ethyl ester (GEE) labeling. The first experiment examines the three full
      length WT isoforms in their tetrameric state and finds that the overall
      structures are similar, with the exception of M108 in ApoE4 which is more solvent
      accessible in this isoform than in ApoE2 and ApoE3. The second experiment
      provides clear evidence, from a comparison of the footprinting results of the
      wild-type proteins and a monomeric mutant, that several residues in regions 183
      205 and 232-251 are involved in self-association.

PMID- 21848290
TI  - Theoretical study of magnesium fluoride in aqueous solution.
AB  - A series of magnesium fluorides (MgF(n)(2-n)), multiply charged anions, in the
      gas phase and in aqueous solution were theoretically studied with a hybrid
      approach of quantum chemistry and statistical mechanics, called RISM-SCF-SEDD
      theory. In the gas phase, MgF(3)(-) is the most stable species among the
      complexes (n = 1-6). In contrast, due to compensation between the intramolecular
      energy and solvation free energy, the stabilities of a number of complexes with
      different n are comparable in aqueous solution. Based on accurate evaluation of
      free energy change, the mole fraction of MgF(4)(2-) is the highest in the range
      from pF = 2.0 to 3.0 of aqueous solution. This is consistent with the available
      PDB data of the enzymes that catalyze the phosphoryl transfer reactions. The
      hydration structures of magnesium fluorides obtained by RISM-SCF-SEDD theory
      provide insight into their structural changes from the gas phase to aqueous
      solution.

PMID- 21848291
TI  - Size of elementary clusters and process period in silver nanoparticle formation.
AB  - The time dependence of small-angle X-ray scattering (SAXS) curves for silver
      nanoparticle formation was followed in situ at a time resolution of 0.18 ms,
      which is 3 orders of magnitude higher than that used in previous reports (ca. 100
      ms). The starting materials were silver nitrate solutions that were reacted with
      reducing solutions containing trisodium citrate. The SAXS analyses showed that
      silver nanoparticles were formed in three distinct periods from a peak diameter
      of ca. 0.7 nm (corresponding to the size of a Ag(13) cluster) during the
      nucleation and the early growth period. The Ag(13) clusters are most likely
      elementary clusters that agglomerate to form silver nanoparticles.

PMID- 21848289
TI  - Designed hairpin peptides interfere with amyloidogenesis pathways: fibril
      formation and cytotoxicity inhibition, interception of the preamyloid state.
AB  - Hairpin peptides bearing cross-strand Trp-Trp and Tyr-Tyr pairs at non-H-bonded
      strand sites modulate the aggregation of two unrelated amyloidogenic systems,
      human pancreatic amylin (hAM) and alpha-synuclein (alpha-syn), associated with
      type II diabetes and Parkinson's disease, respectively. In the case of hAM, we
      have previously reported that inhibition of amyloidogenesis is observed as an
      increase in the lag time to amyloid formation and a diminished thioflavin (ThT)
      fluorescence response. In this study, a reduced level of hAM fibril formation is
      confirmed by transmission electron microscopy imaging. Several of the hairpins
      tested were significantly more effective inhibitors than rat amylin. Moreover, a
      marked inhibitory effect on hAM-associated cytotoxicity by the more potent
      hairpin peptide is demonstrated. In the case of alpha-syn, the dominant effect of
      active hairpins was, besides a weakened ThT fluorescence response, the earlier
      appearance of insoluble aggregates that do not display amyloid characteristics
      with the few fibrils observed having abnormal morphology. We attribute the
      alteration of the alpha-synuclein aggregation pathway observed to the capture of
      a preamyloid state and diversion to nonamyloidogenic aggregates. These beta
      hairpins represent a new class of amyloid inhibitors that bear no sequence
      similarity to the amyloid-producing polypeptides that are inhibited. A
      mechanistic rationale for these effects is proposed.

PMID- 21848292
TI  - Novel small stable gold nanoparticles bearing fluorescent cysteine-coumarin
      probes as new metal-modulated chemosensors.
AB  - Emissive molecular probes based on amino acid moieties are very appealing because
      of their application as new building blocks in peptide synthesis. Two new
      bioinspired coumarin probes (L1 and L2) were synthesized and fully characterized
      by elemental analysis, infrared, (1)H NMR, (13)C NMR, UV-vis absorption and
      emission spectroscopy, matrix-assisted laser desorption-ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS), lifetime measurements, and X-ray crystal
      diffraction. Their sensing ability toward alkaline earth, transition, and post
      transition metal ions (Ca(2+), Zn(2+), Cd(2+), Cu(2+), Ni(2+), Hg(2+), Ag(+), and
      Al(3+)) and their acid-base behavior (H(+), OH(-)) were explored in absolute
      ethanol by absorption and fluorescence spectroscopy. Compound L1 shows a strong
      complexation constant with the soft metal ions Zn(2+), Cd(2+), and Ag(+).
      Compound L2 shows a high fluorescence quantum yield, and it could be used as a
      non-pH-dependent fluorescent biological probe. Very small gold nanoparticles
      (AuNPs) using compounds L1 and L2 as stabilizers were obtained by using a
      reductive method and were characterized by UV-vis, light scattering, and
      transmission electron microscopy (TEM). Dynamic light scattering and TEM studies
      show that the formation of small nanoparticles is around 4.27 +/- 0.64 nm for L1
      and around 2.69 +/- 0.96 nm for L2. The new stable Cou@AuNPs behaved as
      supramolecular chemosensors, which have been selective for the heavy element
      Hg(2+), with a concomitant change of color from pink to dark red/brown and an
      increase of size up to 100-fold.

PMID- 21848293
TI  - Sterostreins A-E, new terpenoids from cultures of the Basidiomycete Stereum
      ostrea BCC 22955.
AB  - Sterostreins A-E (1, 2, 3a/3b, 4, and 5), five novel terpenoids, were isolated
      from cultures of the mushroom fungus Stereum ostrea BCC 22955. Sterostrein A (1)
      exhibited antimalarial activity (IC(50) 2.3 MUg/mL) and cytotoxicity (IC(50) 5.3
      38 MUg/mL).

PMID- 21848295
TI  - Environmentally friendly slow-release nitrogen fertilizer.
AB  - To sustain the further world population, more fertilizers are required, which may
      become an environmental hazard, unless adequate technical and socioeconomic
      impacts are addressed. In the current study, slow-release formulations of
      nitrogen fertilizer were developed on the basis of natural attapulgite (APT)
      clay, ethylcellulose (EC) film, and sodium
      carboxymethylcellulose/hydroxyethylcellulose (CMC/HEC) hydrogel. The structural
      and chemical characteristics of the product were examined. The release profiles
      of urea, ammonium sulfate, and ammonium chloride as nitrogen fertilizer
      substrates were determined in soil. To further compare the release profiles of
      nitrogen from different fertilizer substrates, a mathematical model for nutrient
      release from the coated fertilizer was applied to calculate the diffusion
      coefficient D. The influence of the product on water-holding and water-retention
      capacities of soil was determined. The experimental data indicated that the
      product can effectively reduce nutrient loss, improve use efficiency of water,
      and prolong irrigation cycles in drought-prone environments.

PMID- 21848296
TI  - Carrier control of graphene driven by the proximity effect of functionalized self
      assembled monolayers.
AB  - We demonstrated the carrier control of graphene by employing the electrostatic
      potential produced by several types of self-assembled monolayer (SAM) formed on
      SiO(2) substrates. For single layer graphene on perfluoroalkylsilane-SAM, the
      stiffening of the Raman G-band indicates a large down shift of the Fermi level (~
      0.8 eV) by accumulated hole carriers. Meanwhile, aminoarylsilane-SAM accumulated
      electron carriers, which compensate the hole carriers doped by adsorbed molecules
      under the ambient atmosphere, in graphene. The present results and their
      theoretical analysis reveal that the use of the dipole moments of SAM molecules
      can systematically modulate the electrostatic potential affecting graphene
      without destroying its intrinsic electronic structure and let us know that the
      proximity effect of the SAMs is a promising way in developing graphene-based
      solid state electronics.

PMID- 21848297
TI  - An easily accessible isoindigo-based polymer for high-performance polymer solar
      cells.
AB  - A new, low-band-gap alternating copolymer consisting of terthiophene and
      isoindigo has been designed and synthesized. Solar cells based on this polymer
      and PC(71)BM show a power conversion efficiency of 6.3%, which is a record for
      polymer solar cells based on a polymer with an optical band gap below 1.5 eV.
      This work demonstrates the great potential of isoindigo moieties as electron
      deficient units for building donor-acceptor-type polymers for high-performance
      polymer solar cells.

PMID- 21848298
TI  - Mn2+-bonded reduced graphene oxide with strong radiative recombination in broad
      visible range caused by resonant energy transfer.
AB  - The photoluminescence (PL) characteristics of Mn(2+)-bonded reduced graphene
      oxide (rGO) are studied in details. The Mn(2+)-bonded rGO is synthesized using
      MnO(2)-decorated GO as the intermediate products and ideal tunable PL is obtained
      by enhancing the long-wavelength (450-550 nm) emission. The PL spectra excited by
      different wavelengths are analyzed to elucidate the mechanism, and the resonant
      energy transfer between Mn(2+) and sp(2) clusters of the rGO appears to be
      responsible for the enhanced long-wavelength emission. To examine the effect of
      Mn(2+) on the long-wavelength emission from the Mn(2+)-bonded rGO, the PL
      characteristics of Mn(2+)-bonded rGO with smaller Mn concentrations are studied
      and weaker emission is observed. Our theoretical calculation corroborates the
      experimental results.

PMID- 21848299
TI  - Local voltage drop in a single functionalized graphene sheet characterized by
      Kelvin probe force microscopy.
AB  - We studied the local voltage drop in functionalized graphene sheets of subMUm
      size under external bias conditions by Kelvin probe force microscopy. Using this
      noninvasive experimental approach, we measured ohmic current-voltage
      characteristics and an intrinsic conductivity of about 3.7 * 10(5) S/m
      corresponding to a sheet resistance of 2.7 kOmega/sq under ambient conditions for
      graphene produced via thermal reduction of graphite oxide. The contact
      resistivity between functionalized graphene and metal electrode was found to be
      <6.3 * 10(-7) Omegacm(2).

PMID- 21848301
TI  - Phase transitions and spatially ordered counterion association in ionic-lipid
      membranes: theory versus experiment.
AB  - Aqueous dispersions of phosphatidylglycerol (PG) lipids may present an anomalous
      chain-melting transition at low ionic strengths, as seen by different
      experimental techniques such as calorimetry or light scattering. The anomaly
      disappears at high ionic strengths or for longer acyl-chain lengths. In this
      article, we use a statistical model for the bilayer that distinguishes both lipid
      chain and headgroup states in order to compare model and experimental
      thermotropic and electrical properties. The effective van der Waals interactions
      among hydrophobic chains compete with the electrostatic repulsions between polar
      headgroups, which may be ionized (counterion dissociated) or electrically neutral
      (associated with counterions). Electric degrees of freedom introduce new
      thermotropic charge-ordered phases in which headgroup charges may be spatially
      ordered, depending on the electrolyte ionic strength, introducing a new rationale
      for experimental data on PGs. The thermal phases presented by the model for
      different chain lengths, at fixed ionic strength, compare well with an
      experimental phase diagram constructed on the basis of differential scanning
      calorimetry profiles. In the case of dispersions of DMPG (dimyristoyl
      phosphatidylglycerol) with added monovalent salt, the model properties reproduce
      the main features displayed by data from differential scanning calorimetry as
      well as the characteristic profile for the degree of ionization of the bilayer
      surface across the anomalous transition region, obtained from the theoretical
      interpretation of electrokinetic (conductivity and electrophoretic mobility)
      measurements.

PMID- 21848300
TI  - Dual catalysis in enantioselective oxidopyrylium-based [5 + 2] cycloadditions.
AB  - A new method for effecting catalytic enantioselective intramolecular [5 + 2]
      cycloadditions based on oxidopyrylium intermediates is reported. The dual
      catalyst system consists of a chiral primary aminothiourea and a second achiral
      thiourea. Experimental evidence points to a new type of cooperative catalysis
      with each species being necessary to generate a reactive pyrylium ion pair that
      undergoes subsequent cycloaddition with high enantioselectivity.

PMID- 21848302
TI  - Cascade reaction of isatins with heterocyclic ketene aminals: synthesis of
      imidazopyrroloquinoline derivatives.
AB  - A concise and efficient route for the synthesis of highly substituted
      imidazopyrroloquinoline derivatives by simply refluxing a reaction mixture of
      different types of isatins and heterocyclic ketene aminals (HKAs) by acetic acid
      was developed. This method is suitable for combinatorial and parallel syntheses
      in drug discovery; consequently, a library of highly substituted
      imidazopyrroloquinoline derivatives was rapidly constructed using the present
      protocol.

PMID- 21848303
TI  - Phytoscreening for chlorinated solvents using rapid in vitro SPME sampling:
      application to urban plume in Verl, Germany.
AB  - Rapid detection and delineation of contaminants in urban settings is critically
      important in protecting human health. Cores from trees growing above a plume of
      contaminated groundwater in Verl, Germany, were collected in 1 day, with
      subsequent analysis and plume mapping completed over several days. Solid-phase
      microextraction (SPME) analysis was applied to detect tetrachloroethene (PCE) and
      trichloroethene (TCE) to below nanogram/liter levels in the transpiration stream
      of the trees. The tree core concentrations showed a clear areal correlation to
      the distribution of PCE and TCE in the groundwater. Concentrations in tree cores
      were lower than the underlying groundwater, as anticipated; however, the tree
      core water retained the PCE:TCE signature of the underlying groundwater in the
      urban, populated area. The PCE:TCE ratio can indicate areas of differing
      degradation activity. Therefore, the phytoscreening analysis was capable not only
      of mapping the spatial distribution of groundwater contamination but also of
      delineating zones of potentially differing contaminant sources and degradation.
      The simplicity of tree coring and the ability to collect a large number of
      samples in a day with minimal disruption or property damage in the urban setting
      demonstrates that phytoscreening can be a powerful tool for gaining
      reconnaissance-level information on groundwater contaminated by chlorinated
      solvents. The use of SPME decreases the detection level considerably and
      increases the sensitivity of phytoscreening as an assessment, monitoring, and
      phytoforensic tool. With rapid, inexpensive, and noninvasive methods of detecting
      and delineating contaminants underlying homes, as in this case, human health can
      be better protected through screening of broader areas and with far faster
      response times.

PMID- 21848304
TI  - Introducing a new class of N-phosphoryl ynamides via Cu(I)-catalyzed amidations
      of alkynyl bromides.
AB  - We describe here the first synthesis of N-phosphoryl ynamides featuring C- and P
      chirality via copper(I)-catalyzed amidative cross-couplings between
      phosphoramidates and phosphordiamidates with alkynyl bromides. Also featured is a
      tandem aza-Claisen-hetero-[2+2] cycloaddition for the synthesis of N-phosphoryl
      azetidin-2-imines.

PMID- 21848305
TI  - Synthesis of indole and biindolyl triflones: trifluoromethanesulfonylation of
      indoles with Tf2O/TTBP (2,4,6-tri-tert-butylpyridine) system.
AB  - A convenient synthesis of indole triflones is reported. N-Alkyl, aryl and N-H
      indole triflones were obtained in 82-96% yields by the Tf(2)O/TTBP System.
      Biindolyl triflones were accessed in 51-81% yields for the first time by simple
      treatment of the resulting indole triflones with a base and without any use of
      organometallic chemistry. An environmentally friendly solvent, Solkane 365/227,
      can be substituted for this process without any loss of efficiency.

PMID- 21848306
TI  - Structure of the USP15 N-terminal domains: a beta-hairpin mediates close
      association between the DUSP and UBL domains.
AB  - Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated
      regulation of protein degradation and cellular signaling through catalyzing the
      ubiquitin deconjugation reaction of a discrete number of substrates. It
      influences the stability of adenomatous polyposis coli, IkappaBalpha, caspase-3,
      and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and
      USP11 related through a shared presence of N-terminal "domain present in
      ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU
      subfamily). Here we report the 1.5 A resolution crystal structure of the human
      USP15 N-terminal domains revealing a 80 A elongated arrangement with the DU
      domains aligned in tandem. This architecture is generated through formation of a
      defined interface that is dominated by an intervening beta-hairpin structure (DU
      finger) that engages in an intricate hydrogen-bonding network between the
      domains. The UBL domain is closely related to ubiquitin among beta-grasp folds
      but is characterized by the presence of longer loop regions and different surface
      characteristics, indicating that this domain is unlikely to act as ubiquitin
      mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals
      that the main DU interdomain contacts are conserved. Analytical
      ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments
      revealed that USP15 DU is monomeric in solution. Our data provide a framework to
      advance study of the structure and function of the DU subfamily.

PMID- 21848307
TI  - Electronic phase coherence in InAs nanowires.
AB  - Magnetotransport measurements at low temperatures have been performed on InAs
      nanowires grown by In-assisted molecular beam epitaxy. Information on the
      electron phase coherence is obtained from universal conductance fluctuations
      measured in a perpendicular magnetic field. By analysis of the universal
      conductance fluctuations pattern of a series of nanowires of different length,
      the phase-coherence length could be determined quantitatively. Furthermore,
      indications of a pronounced flux cancelation effect were found, which is
      attributed to the topology of the nanowire. Additionally, we present measurements
      in a parallel configuration between wire and magnetic field. In contrast to
      previous results on InN and InAs nanowires, we do not find periodic oscillations
      of the magnetoconductance in this configuration. An explanation of this behavior
      is suggested in terms of the high density of stacking faults present in our InAs
      wires.

PMID- 21848308
TI  - Silicon-nanowire-based CMOS-compatible field-effect transistor nanosensors for
      ultrasensitive electrical detection of nucleic acids.
AB  - We herein report the design of a novel semiconducting silicon nanowire field
      effect transistor (SiNW-FET) biosensor array for ultrasensitive label-free and
      real-time detection of nucleic acids. Highly responsive SiNWs with narrow sizes
      and high surface-to-volume-ratios were "top-down" fabricated with a complementary
      metal oxide semiconductor compatible anisotropic self-stop etching technique.
      When SiNWs were covalently modified with DNA probes, the nanosensor showed highly
      sensitive concentration-dependent conductance change in response to specific
      target DNA sequences. This SiNW-FET nanosensor revealed ultrahigh sensitivity for
      rapid and reliable detection of 1 fM of target DNA and high specificity single
      nucleotide polymorphism discrimination. As a proof-of-concept for multiplex
      detection with this small-size and mass producible sensor array, we demonstrated
      simultaneous selective detection of two pathogenic strain virus DNA sequences
      (H1N1 and H5N1) of avian influenza.

PMID- 21848309
TI  - Relationship between conformational stability and amplification efficiency of
      prions.
AB  - Recent studies demonstrated that the efficiency, rate, and yield of prion
      amplification in vitro could be substantially improved by supplementing protein
      misfolding cyclic amplification (PMCA) with Teflon beads [Gonzalez-Montalban et
      al. (2011) PLoS Pathog. 7, e1001277]. Here we employed the new PMCA format with
      beads (PMCAb) to gain insight into the mechanism of prion amplification. Using a
      panel of six hamster prion strains, the effect of beads on amplification was
      found to be strain-specific, with the largest improvements in efficiency observed
      for strains with the highest conformational stability. This result suggests a
      link between PrP(Sc) conformational stability and its fragmentation rate and that
      beads improved amplification by assisting fragmentation. Furthermore, while
      exploring the PrP(Sc)-independent bead effect mechanism, a synergy between the
      effects of RNA and beads on amplification was observed. Consistent with previous
      studies, amplification of all six hamster strains tested here was found to be RNA
      dependent. Under sonication conditions used for PMCA, large RNA molecules were
      found to degrade into smaller fragments of a size that was previously shown to be
      the most effective in facilitating prion conversion. We speculate that sonication
      induced changes in RNA size distribution could be one of the rate-limiting steps
      in prion amplification.

PMID- 21848310
TI  - Dynamics of a disturbed sessile drop measured by atomic force microscopy (AFM).
AB  - A new method for studying the dynamics of a sessile drop by atomic force
      microscopy (AFM) is demonstrated. A hydrophobic microsphere (radius, r ~ 20-30
      MUm) is brought into contact with a small sessile water drop resting on a
      polytetrafluoroethylene (PTFE) surface. When the microsphere touches the liquid
      surface, the meniscus rises onto it because of capillary forces. Although the
      microsphere volume is 6 orders of magnitude smaller than the drop, it excites the
      normal resonance modes of the liquid interface. The sphere is pinned at the
      interface, whose small (<100 nm) oscillations are readily measured with AFM.
      Resonance oscillation frequencies were measured for drop volumes between 5 and
      200 MUL. The results for the two lowest normal modes are quantitatively
      consistent with continuum calculations for the natural frequency of hemispherical
      drops with no adjustable parameters. The method may enable sensitive measurements
      of volume, surface tension, and viscosity of small drops.

PMID- 21848312
TI  - Growth of InAs quantum dots on GaAs nanowires by metal organic chemical vapor
      deposition.
AB  - InAs quantum dots (QDs) are grown epitaxially on Au-catalyst-grown GaAs nanowires
      (NWs) by metal organic chemical vapor deposition (MOCVD). These QDs are about 10
      30 nm in diameter and several nanometers high, formed on the {112} side facets of
      the GaAs NWs. The QDs are very dense at the base of the NW and gradually sparser
      toward the top until disappearing at a distance of about 2 MUm from the base. It
      can be concluded that these QDs are formed by adatom diffusion from the substrate
      as well as the sidewalls of the NWs. The critical diameter of the GaAs NW that is
      enough to form InAs QDs is between 120 and 160 nm according to incomplete
      statistics. We also find that these QDs exhibit zinc blende (ZB) structure that
      is consistent with that of the GaAs NW and their edges are faceted along
      particular surfaces. This hybrid structure may pave the way for the development
      of future nanowire-based optoelectronic devices.

PMID- 21848313
TI  - On the biotransformation of ent-trachylobane to ent-kaur-11-ene diterpenes.
AB  - The microbiological transformation of trachinodiol (1) by the fungus Mucor
      plumbeus afforded the corresponding 1alpha, 2alpha, 3alpha, and 17-hydroxy
      derivatives (2-4 and 6), respectively. 7beta,16alpha,18-Trihydroxy-ent-kaur-11
      ene (sicanatriol) (5) was also obtained in this feeding. The biotransformation of
      1 to give 5 by this fungus may occur by enzymatic abstraction of a hydrogen atom,
      allylic to the cyclopropane ring, and subsequent cleavage of this ring. This
      route is similar to that postulated by us in plants of the genus Sideritis, where
      ent-trachylobane and ent-kaur-11-ene diterpenes coexist. This study confirms that
      hydroxylation of diterpenes by M. plumbeus occurs preferably at ring A carbons.

PMID- 21848311
TI  - Tolerance to changes in membrane lipid composition as a selected trait of
      membrane proteins.
AB  - Membrane lipid composition can vary dramatically across the three domains of life
      and even within single organisms. Here we review evidence that the lipid-exposed
      surfaces of membrane proteins have generally evolved to maintain correct
      structure and function in the face of major changes in lipid composition. Such
      tolerance has allowed evolution to extensively remodel membrane lipid
      compositions during the emergence of new species without having to extensively
      remodel the associated membrane proteins. The tolerance of membrane proteins also
      permits single-cell organisms to vary their membrane lipid composition in
      response to their changing environments and allows dynamic and organelle-specific
      variations in the lipid compositions of eukaryotic cells. Membrane protein
      structural biology has greatly benefited from this seemingly intrinsic property
      of membrane proteins: the majority of structures determined to date have been
      characterized under model membrane conditions that little resemble those of
      native membranes. Nevertheless, with a few notable exceptions, most
      experimentally determined membrane protein structures appear, to a good
      approximation, to faithfully report on native structure.

PMID- 21848314
TI  - A new route toward semiconductor nanospintronics: highly Mn-doped GaAs nanowires
      realized by ion-implantation under dynamic annealing conditions.
AB  - We report on highly Mn-doped GaAs nanowires (NWs) of high crystalline quality
      fabricated by ion beam implantation, a technique that allows doping
      concentrations beyond the equilibrium solubility limit. We studied two approaches
      for the preparation of Mn-doped GaAs NWs: First, ion implantation at room
      temperature with subsequent annealing resulted in polycrystalline NWs and phase
      segregation of MnAs and GaAs. The second approach was ion implantation at
      elevated temperatures. In this case, the single-crystallinity of the GaAs NWs was
      maintained, and crystalline, highly Mn-doped GaAs NWs were obtained. The
      electrical resistance of such NWs dropped with increasing temperature (activation
      energy about 70 meV). Corresponding magnetoresistance measurements showed a
      decrease at low temperatures, indicating paramagnetism. Our findings suggest
      possibilities for future applications where dense arrays of GaMnAs nanowires may
      be used as a new kind of magnetic material system.

PMID- 21848315
TI  - Solid supported chemical syntheses of both components of the lantibiotic lacticin
      3147.
AB  - Lantibiotics are antimicrobial peptides produced by bacteria. Some are employed
      for food preservation, whereas others have therapeutic potential due to their
      activity against organisms resistant to current antibiotics. They are ribosomally
      synthesized and posttranslationally modified by dehydration of serine and
      threonine residues followed by attack of thiols of cysteines to form monosulfide
      lanthionine and methyllanthionine rings, respectively. Chemical synthesis of
      peptide analogues is a powerful method to verify stereochemistry and access
      structure-activity relationships. However, solid supported synthesis of
      lantibiotics has been difficult due to problems in generating lanthionines and
      methyllanthionines with orthogonal protection and good stereochemical control. We
      report the solid-phase syntheses of both peptides of a two-component lantibiotic,
      lacticin 3147. Both successive and interlocking ring systems were synthesized on
      resin, thereby providing a general methodology for this family of natural
      products.

PMID- 21848316
TI  - Autocatalytic reaction in hydrolysis of difructose anhydride III.
AB  - Hydrolysis of several polysaccharides in neutral and weak acid environment has
      been shown to exhibit autocatalytic behavior. Because the pH value of the
      solution decreases during hydrolysis, it has been proposed that proton is the
      catalyst of the autocatalytic reaction. We monitored the hydrolysis of difructose
      anhydride III (DFA III) in both strong and weak acid environment using Raman
      spectroscopy and found that it is also an autocatalytic reaction. Its Raman
      signatures were analyzed with ab initio method. When the reaction product,
      fructose, is added in the beginning of the reaction, the speed of hydrolysis
      increases to a magnitude that cannot be explained by the rate enhancement due to
      a decrease in the pH value, indicating that proton alone is not an effective
      catalyst for the reaction. It is the combination of proton and a certain form of
      reaction product such as monosaccharide or its derivatives that catalyzes the
      hydrolysis of difructose anhydride III. Similar results are observed in the
      hydrolysis of cellobiose, suggesting the universality of this autocatalytic
      reaction. Our findings provide the first clue to a new autocatalytic pathway in
      the hydrolysis of polysaccharides.

PMID- 21848317
TI  - Carbon nanotube field effect transistors with suspended graphene gates.
AB  - Novel field effect transistors with suspended graphene gates are demonstrated. By
      incorporating mechanical motion of the gate electrode, it is possible to improve
      the switching characteristics compared to a static gate, as shown by a
      combination of experimental measurements and numerical simulations. The
      mechanical motion of the graphene gate is confirmed by using atomic force
      microscopy to directly measure the electrostatic deflection. The device geometry
      investigated here can also provide a sensitive measurement technique for
      detecting high-frequency motion of suspended membranes as required, e.g., for
      mass sensing.

PMID- 21848318
TI  - Assessing atropisomer axial chirality in drug discovery and development.

PMID- 21848319
TI  - Electrochemical DNA analysis with a supramolecular assembly of naphthalene
      diimide, ferrocene, and beta-cyclodextrin.
AB  - Naphthalene diimide 1 bearing ferrocene and beta-cyclodextrin (beta-CD) was
      prepared. Its half-wave potential at 420 mV shifted 40-50 mV upon addition of an
      excess of adamantylamine, suggesting that the ferrocene of 1 is included in the
      cavity of beta-CD intramolecularly to form a pseudocyclic structure. This unique
      architecture is retained even where 1 is bound to calf thymus DNA to give rise to
      a catenane-like structure. Morphology of the DNA complex with 1 was further
      explored by atomic force microscopy to reveal that the DNA strand tends to bend
      as the amount of 1 on it increases. Presumably, intermolecular, yet intrastrand,
      inclusion of ferrocene into beta-CD is responsible for this phenomenon. The
      resulting globular structure reverted partially by the addition of
      adamantylamine. At a low ratio of 1 to DNA, a novel reduction peak appeared at
      320 mV in the differential pulse voltammograms of 1 at the expense of the 420 mV
      peak. The peak current of the former was proportional to the DNA concentration,
      thereby enabling quantitation of DNA in a signal-on way. Likewise, a polymerase
      chain reaction (PCR) product of 754 bp was analyzed successfully with a detection
      limit of 13 nM.

PMID- 21848320
TI  - Contact and fumigant toxicity of a botanical-based feeding deterrent of the
      stable fly, Stomoxys calcitrans (Diptera: Muscidae).
AB  - The stable fly, Stomoxys calcitrans (L.), has been considered one of the most
      serious biting flies of confined and pastured livestock. The economic losses
      caused by the stable fly to the cattle industry in the United States exceed $2
      billion annually. Current practices for managing stable flies using insecticides
      provide only marginal control. Insecticide resistance has also been recently
      reported in stable flies. The present study reports the use of plant-based
      insecticides, for example, essential oils, as alternatives for managing this fly
      pest. The toxicity of several plant essential oils and selected ingredient
      compounds was evaluated by contact and fumigant toxicity bioassays. Catnip oil
      (20 mg dosage) showed the highest toxicity against stable flies, the shortest
      knock-down time (~7 min), and the quickest lethal time (~19 min). Toxicity levels
      similar to catnip oil were found among three insect repellent compounds (N,N
      diethyl-3-methylbenzamide, 2-methylpiperidinyl-3-cyclohexene-1-carboxamide,
      (1S,2'S)-2-methylpiperidinyl-3-cyclohexene-1-carboxamide). No differences in
      knock-down and lethal times were found among the catnip oil and its two active
      ingredient compounds. Similar stable fly mortality was observed using a 20 mg
      dose of catnip oil in a modified K&D system and a fumigant jar. When catnip oil
      was topically applied to stable flies, the least lethal dose was 12.5 MUg/fly,
      and a 50 MUg/fly dose resulted in 100% mortality. The blood-feeding behavior of
      stable flies was also negatively affected by the topical application of catnip
      oil, and the effect was dose-dependent. This study demonstrated that catnip oil
      has both contact and fumigant toxicity against the stable fly and thus has the
      potential as an alternative for stable fly control.

PMID- 21848321
TI  - Shear adhesion strength of thermoplastic gecko-inspired synthetic adhesive
      exceeds material limits.
AB  - Natural gecko array wearless dynamic friction has recently been reported for
      30,000 cycles on a smooth substrate. Following these findings, stiff polymer
      gecko-inspired synthetic adhesives have been proposed for high-cycle applications
      such as robot feet. Here we examine the behavior of high-density polyethylene
      (HDPE) and polypropylene (PP) microfiber arrays during repeated cycles of
      engagement on a glass surface, with a normal preload of less than 40 kPa. We find
      that fiber arrays maintained 54% of the original shear stress of 300 kPa after
      10,000 cycles, despite showing a marked plastic deformation of fiber tips. This
      deformation could be due to shear-induced plastic creep of the fiber tips from
      high adhesion forces, adhesive wear, or thermal effects. We hypothesize that a
      fundamental material limit has been reached for these fiber arrays and that
      future gecko synthetic adhesive designs must take into account the high adhesive
      forces generated to avoid damage. Although the synthetic material and natural
      gecko arrays have a similar elastic modulus, the synthetic material does not show
      the same wear-free dynamic friction as the gecko.

PMID- 21848322
TI  - Structure and NMR spectra of some [2.2]paracyclophanes. The dilemma of
      [2.2]paracyclophane symmetry.
AB  - Density functional theory (DFT) quantum chemical calculations of the structure
      and NMR parameters for highly strained hydrocarbon [2.2]paracyclophane 1 and its
      three derivatives are presented. The calculated NMR parameters are compared with
      the experimental ones. By least-squares fitting of the (1)H spectra, almost all
      J(HH) coupling constants could be obtained with high accuracy. Theoretical
      vicinal J(HH) couplings in the aliphatic bridges, calculated using different
      basis sets (6-311G(d,p), and Huz-IV) reproduce the experimental values with
      essentially the same root-mean-square (rms) error of about 1.3 Hz, regardless of
      the basis set used. These discrepancies could be in part due to a considerable
      impact of rovibrational effects on the observed J(HH) couplings, since the latter
      show a measurable dependence on temperature. Because of the lasting literature
      controversies concerning the symmetry of parent compound 1, D(2h) versus D(2), a
      critical analysis of the relevant literature data is carried out. The symmetry
      issue is prone to confusion because, according to some literature claims, the two
      hypothetical enantiomeric D(2) structures of 1 could be separated by a very low
      energy barrier that would explain the occurrence of rovibrational effects on the
      observed vicinal J(HH) couplings. However, the D(2h) symmetry of 1 with a flat
      energy minimum could also account for these effects.

PMID- 21848323
TI  - Uranyl ion extraction with conventional PUREX/TRUEX ligands assessed by
      electroanalytical chemistry at micro liquid/liquid interfaces.
AB  - The facilitated ion transfer (FIT) of uranyl or dioxouranium (UO(2)(2+)) was
      studied electrochemically using a micro interface between two immiscible
      electrolytic solutions (micro-ITIES) in order to evaluate the complexation
      stoichiometry and complexation constants (beta) of two widely used ligands in
      spent fuel reprocessing: tributylphosphate (TBP) and octyl(phenyl)-N,N
      diisobutylcarbamoylmethyl-phosphine oxide (CMPO). For the first time, discrete
      interfacial complexation reaction steps of varying uranyl to the two ligands
      ratios were resolved using the micro-ITIES hosted at the tip of a 25 MUm diameter
      glass capillary. Two stoichiometries for UO(2)NO(3)TBP(n)(+) were determined
      including n = 3 and 4 with beta values of 3.2 * 10(11) and 3.9 * 10(13),
      respectively. Subsequently, three distinct complexation reactions of CMPO with
      UO(2)(2+) were discovered corresponding to UO(2)NO(3)CMPO(2)(+),
      UO(2)NO(3)CMPO(3)(+), and UO(2)CMPO(5)(2+) whose respective complexation
      constants were determined to be 8.0 * 10(11), 8.8 * 10(14), and 6.5 * 10(32). The
      participation of nitrate anions in these complexation reactions is also
      discussed.

PMID- 21848325
TI  - The glmS ribozyme tunes the catalytically critical pK(a) of its coenzyme
      glucosamine-6-phosphate.
AB  - The glmS ribozyme riboswitch is the first known natural catalytic RNA that
      employs a small-molecule cofactor. Binding of glucosamine-6-phosphate (GlcN6P)
      uncovers the latent self-cleavage activity of the RNA, which adopts a
      catalytically competent conformation that is nonetheless inactive in the absence
      of GlcN6P. Structural and analogue studies suggest that the amine of GlcN6P
      functions as a general acid-base catalyst, while its phosphate is important for
      binding affinity. However, the solution pK(a) of the amine is 8.06 +/- 0.05,
      which is not optimal for proton transfer. Here we used Raman crystallography
      directly to determine the pK(a)'s of GlcN6P bound to the glmS ribozyme. Binding
      to the RNA lowers the pK(a) of the amine of GlcN6P to 7.26 +/- 0.09 and raises
      the pK(a) of its phosphate to 6.35 +/- 0.09. Remarkably, the pK(a)'s of these two
      functional groups are unchanged from their values for free GlcN6P (8.06 +/- 0.05
      and 5.98 +/- 0.05, respectively) when GlcN6P binds to the catalytically inactive
      but structurally unperturbed G40A mutant of the ribozyme, thus implicating the
      ribozyme active site guanine in pK(a) tuning. This is the first demonstration
      that a ribozyme can tune the pK(a) of a small-molecule ligand. Moreover, the
      anionic glmS ribozyme in effect stabilizes the neutral amine of GlcN6P by
      lowering its pK(a). This is unprecedented and illustrates the chemical
      sophistication of ribozyme active sites.

PMID- 21848326
TI  - Oxidative dinuclear addition of a PdI-PdI moiety to arenes: generation of MU
      eta3:eta3-arene-Pd(II)2 species.
AB  - We report the oxidative dinuclear addition of a Pd(I)-Pd(I) bond to arenes. The
      oxidative dinuclear addition products, which have a bi-pi-allyl-type arene
      dipalladium(II) structure, were obtained from [2.2]paracyclophane, anthracene,
      tetracene, and pentacene. A systematic study of the reaction of
      [Pd(2)(CH(3)CN)(6)][BF(4)](2) with benzene and polyacenes showed that the larger
      polyacenes, tetracene and pentacene, afforded the oxidative dinuclear addition
      products, while benzene, naphthalene, and anthracene gave the pi-sandwich Pd(I)
      Pd(I) complexes.

PMID- 21848327
TI  - Autocatalysis and surface catalysis in the reduction of imines by SmI2.
AB  - The reduction of the three imines, N-benzylidene aniline (BAI), N
      benzylidenemethylamine (BMI), and benzophenone imine (BPI), with SmI(2) gives the
      reduced as well as coupled products. The reactions were found to be autocatalytic
      due to the formation of the trivalent samarium in the course of the reaction.
      When preprepared SmI(3) was added to the reaction mixture, the reaction rate
      increased significantly. However, the kinetics were found to be of zero order in
      SmI(2). This type of behavior is typical of surface catalysis with saturation of
      the catalytic sites. Although no solids are visible to the naked eye, the
      existence of microcrystals was proven by light microscopy as well as by dynamic
      light scattering analysis. Although HRTEM shows the existence of quantum dots in
      the solid, we were unable to make a direct connection between the existence of
      the quantum dots and the catalytic phenomenon. In the uncatalyzed reaction, the
      order of reactivity is BPI > BMI > BAI. This order does not conform to the
      electron affinity order of the substrates but rather to the nitrogen lone pair
      accessibility for complexation. This conclusion was further supported by using
      HMPA as a diagnostic probe for the existence of an inner sphere electron transfer
      reaction.

PMID- 21848328
TI  - Facile mechanosynthesis of amorphous zeolitic imidazolate frameworks.
AB  - A fast and efficient mechanosynthesis (ball-milling) method of preparing
      amorphous zeolitic imidazolate frameworks (ZIFs) from different starting
      materials is discussed. Using X-ray total scattering, N(2) sorption analysis, and
      gas pycnometry, these frameworks are indistinguishable from one another and from
      temperature-amorphized ZIFs. Gas sorption analysis also confirms that they are
      nonporous once formed, in contrast to activated ZIF-4, which displays interesting
      gate-opening behavior. Nanoparticles of a prototypical nanoporous substituted
      ZIF, ZIF-8, were also prepared and shown to undergo amorphization.

PMID- 21848324
TI  - When galectins recognize glycans: from biochemistry to physiology and back again.
AB  - In the past decade, increasing efforts have been devoted to the study of
      galectins, a family of evolutionarily conserved glycan-binding proteins with
      multifunctional properties. Galectins function, either intracellularly or
      extracellularly, as key biological mediators capable of monitoring changes
      occurring on the cell surface during fundamental biological processes such as
      cellular communication, inflammation, development, and differentiation. Their
      highly conserved structures, exquisite carbohydrate specificity, and ability to
      modulate a broad spectrum of biological processes have captivated a wide range of
      scientists from a wide spectrum of disciplines, including biochemistry,
      biophysics, cell biology, and physiology. However, in spite of enormous efforts
      to dissect the functions and properties of these glycan-binding proteins, limited
      information about how structural and biochemical aspects of these proteins can
      influence biological functions is available. In this review, we aim to integrate
      structural, biochemical, and functional aspects of this bewildering and ancient
      family of glycan-binding proteins and discuss their implications in physiologic
      and pathologic settings.

PMID- 21848329
TI  - Gravimetric analysis of CO2 adsorption on activated carbon at various pressures
      and temperatures using piezoelectric microcantilevers.
AB  - We investigated the adsorption and desorption of CO(2) on activated carbon using
      piezoelectric microcantilevers. After coating the free end of a cantilever with
      activated carbon, variations in the resonance frequency of the cantilever were
      measured as a function of CO(2) pressure, which is related to mass changes due to
      the adsorption or desorption of CO(2). The pressure-dependent viscous damping
      effects were compensated in the calculation of the CO(2) adsorption capacity of
      the activated carbon by comparing the frequency differences between the coated
      and uncoated cantilevers. The mass sensitivity of the piezoelectric cantilever
      was found to be better than 1 pg. The fractional coverage of CO(2) agreed with a
      Langmuir adsorption isotherm, indicating that a submonolayer of adsorbed CO(2)
      occurred on the surface of the activated carbon under the experimental
      conditions. The heat of adsorption was determined using the Clausius-Clapeyron
      relation and the fractional coverage of CO(2) at various temperatures and
      pressures.

PMID- 21848330
TI  - Regioselective O-substitution of C-undecylresorcin[4]arene.
AB  - Selectively functionalized resorcinarenes were obtained by weak-base-promoted O
      alkylation of C-undecylresorcin[4]arene 1. Tetrasubstituted derivatives with C(4)
      1,3,5,7, C(2v)-1,2,5,6, C(s)-1,2,4,7, and C(i)-1,2,4,6 pattern were obtained in
      workable yields by using K(2)CO(3) as the base in acetone at reflux. The good
      regioselectivity with respect to the statistical distribution was explained in
      terms of preferential formation of H-bonded monoanions. Heptaaroylated
      resorcin[4]arenes were also easily obtained by reaction of 1 with aroyl chlorides
      in pyridine.

PMID- 21848331
TI  - Through-space charge-transfer emitting biphenyls containing a boryl and an amino
      group at the o,o'-positions.
AB  - A new class of organoboron compounds containing a boryl and an amino group at the
      o,o'-positions of biphenyls display bright through-space intramolecular charge
      transfer fluorescence owing to the close contact between the boryl and the amino
      groups. Binding of the fluoride ions results in the remarkable blue shift and
      color change of the fluorescence, enabling colorimetric and ratiometric fluoride
      ion sensing.

PMID- 21848332
TI  - Antimalarial activities of new guanidylimidazole and guanidylimidazoline
      derivatives.
AB  - A series of new guanidylimidazole derivatives was prepared and evaluated in mice
      and Rhesus monkeys infected with malarial sporozoites. The majority of the new
      compounds showed poor metabolic stability and weak in vitro activities in three
      clones of  Plasmodium falciparum.  Compounds 8a, 8h, 9a, 16a, and 16e cured the
      mice infected with sporozoites of P. berghei at 160 and 320 mg/kg/day * 3 po.
      Compounds 8a showed better causal prophylactic activity than primaquine,
      tafenoquine, and Malarone in the Rhesus test. In the radical curative test, 8a
      cured one monkey and delayed relapse of another for 74 days at 30 mg/kg/day * 7
      by im. By oral dosing, 8a delayed relapse 81 days for one and 32 days for other
      vs 11-12 days for control monkeys treated with 10 mg/kg of chloroquine by po
      alone. Compound 8h, which showed superior activity to 8a in mouse test, delayed
      the relapse of treated monkeys for 21-26 days at 30 mg/kg/day * 7 by oral.

PMID- 21848334
TI  - Modeling novel double-in-plane gate electric-double-layer thin-film and nanoscale
      transistors.
AB  - A novel double-in-plane gate oxide-based electric-double-layer (EDL) transistor
      structure applicable to thin-film transistors (TFTs) and nanoscale transistors
      (nanoFETs) is proposed. An equivalent circuit model is provided to illustrate the
      operation mechanism. The double-in-plane gate structure can simplify device
      fabrication effectively and provide unique tunability of threshold. Specifically,
      the gate bias modulates the threshold voltage of TFT and nanoFET and effectively
      controls the transistor subthreshold swing and leakage current. Moreover, the EDL
      gate dielectric can lead to a high gate dielectric capacitance (>1 MUF/cm(2)).
      These simulation results provide basic understanding needed to use and control
      EDL TFTs and nanoFETs in a novel manner.

PMID- 21848333
TI  - Deconvolution of chemical mixtures with high complexity by NMR consensus trace
      clustering.
AB  - Identification and quantification of analytes in complex solution-state mixtures
      are critical procedures in many areas of chemistry, biology, and molecular
      medicine. Nuclear magnetic resonance (NMR) is a unique tool for this purpose
      providing a wealth of atomic-detail information without requiring extensive
      fractionation of the samples. We present three new multidimensional-NMR based
      approaches that are geared toward the analysis of mixtures with high complexity
      at natural (13)C abundance, including approaches that are encountered in
      metabolomics. Common to all three approaches is the concept of the extraction of
      one-dimensional (1D) consensus spectral traces or 2D consensus planes followed by
      clustering, which significantly improves the capability to identify mixture
      components that are affected by strong spectral overlap. The methods are
      demonstrated for covariance (1)H-(1)H TOCSY and (13)C-(1)H HSQC-TOCSY spectra and
      triple-rank correlation spectra constructed from pairs of (13)C-(1)H HSQC and
      (13)C-(1)H HSQC-TOCSY spectra. All methods are first demonstrated for an eight
      compound metabolite model mixture before being applied to an extract from E. coli
      cell lysate.

PMID- 21848335
TI  - Ionic liquids as electrolytes for the development of a robust amperometric oxygen
      sensor.
AB  - A simple Clark-type online electrochemical cell design, consisting of a platinum
      gauze working electrode and incorporating ionic liquids (IL) as electrolytes, has
      been successfully applied for the amperometric sensing of oxygen. Studying ILs
      comprising the bis(trifluoromethylsulfonyl)imide anion, the obtained analytical
      parameters were found to be strongly dependent on the choice of cation. Compared
      with a conventional Clark cell design based on an aqueous supporting electrolyte,
      the modified oxygen sensor achieves substantial improvements in performance and
      stability. A limit of detection for oxygen as low as 0.05 vol %, linearity over
      an oxygen partial pressure between 0% and 20%, and a steady-state response time
      of 2 min was demonstrated, with a stable analytical response shown over the
      examined period of 90 days with no obvious fouling of the electrode surface.
      Based on the attractive physical attributes of ionic liquids (e.g., thermal
      stability beyond 150  degrees C), one can envision intriguing utility in
      nonstandard conditions and long-term online applications, as well as extension to
      the determination of other gases, such as methane and nitric oxide.

PMID- 21848336
TI  - Thiocyanate-capped nanocrystal colloids: vibrational reporter of surface
      chemistry and solution-based route to enhanced coupling in nanocrystal solids.
AB  - Ammonium thiocyanate (NH(4)SCN) is introduced to exchange the long, insulating
      ligands used in colloidal nanocrystal (NC) synthesis. The short, air-stable,
      environmentally benign thiocyanate ligand electrostatically stabilizes a variety
      of semiconductor and metallic NCs in polar solvents, allowing solution-based
      deposition of NCs into thin-film NC solids. NH(4)SCN is also effective in
      replacing ligands on NCs after their assembly into the solid state. The
      spectroscopic properties of this ligand provide unprecedented insight into the
      chemical and electronic nature of the surface of the NCs. Spectra indicate that
      the thiocyanate binds to metal sites on the NC surface and is sensitive to atom
      type and NC surface charge. The short, thiocyanate ligand gives rise to
      significantly enhanced electronic coupling between NCs as evidenced by large
      bathochromic shifts in the absorption spectra of CdSe and CdTe NC thin films and
      by conductivities as high as (2 +/- 0.7) * 10(3) Omega(-1) cm(-1) for Au NC thin
      films deposited from solution. NH(4)SCN treatment of PbTe NC films increases the
      conductivity by 10(13), allowing the first Hall measurements of nonsintered NC
      solids, with Hall effect mobilities of 2.8 +/- 0.7 cm(2)/(V.s). Thiocyanate
      capped CdSe NC thin films form photodetectors exhibiting sensitive
      photoconductivity of 10(-5) Omega(-1) cm(-1) under 30 mW/cm(2) of 488 nm
      illumination with I(photo)/I(dark) > 10(3) and form n-channel thin-film
      transistors with electron mobilities of 1.5 +/- 0.7 cm(2)/(V.s), a current
      modulation of >10(6), and a subthreshold swing of 0.73 V/decade.

PMID- 21848337
TI  - Superfast motion of catalytic microjet engines at physiological temperature.
AB  - There is a great interest in reducing the toxicity of the fuel used to self
      propel artificial nanomachines. Therefore, a method to increase the efficiency of
      the conversion of chemicals into mechanical energy is desired. Here, we employed
      temperature control to increase the efficiency of microjet engines while
      simultaneously reducing the amount of peroxide fuel needed. At physiological
      temperatures, i.e. 37  degrees C, only 0.25% H(2)O(2) is needed to propel the
      microjets at 140 MUm s(-1), which corresponds to three body lengths per second.
      In addition, at 5% H(2)O(2), the microjets acquire superfast speeds, reaching 10
      mm s(-1). The dynamics of motion is altered when the speed is increased; i.e.,
      the motion deviates from linear to curvilinear trajectories. The observations are
      modeled empirically.

PMID- 21848338
TI  - PCL film surfaces conjugated with P(DMAEMA)/gelatin complexes for improving cell
      immobilization and gene transfection.
AB  - Successful gene transfection on a tissue scaffold is of crucial importance in
      facilitating tissue repair and regeneration by enabling the localized production
      of therapeutic drugs. Polycaprolactone (PCL) has been widely adopted as a
      scaffold biomaterial, but its unfavorable cell-adhesion property needs to be
      improved. In this work, the PCL film surface was conjugated with poly((2-dimethyl
      amino)ethyl methacrylate) (P(DMAEMA))/gelatin complexes via surface-initiated
      atom transfer radical polymerization (ATRP) for improving cell immobilization and
      subsequent gene transfection. A simple aminolysis-based method was first used for
      the covalent immobilization of ATRP initiators on the PCL film. Well-defined
      P(DMAEMA) brushes were subsequently prepared via surface-initiated ATRP from the
      initiator-functionalized PCL surfaces. The P(DMAEMA) chains with a pK(a) of 7.0
      7.3 were used for conjugating gelatin with a pI of 4.7 via electrostatic
      interaction. The amount of complexed gelatin increased as that of the grafted
      P(DMAEMA) layer. The cell-adhesion property on the functionalized PCL surface
      could be controlled by adjusting the ratio of P(DMAEMA)/gelatin. It was found
      that the gene transfection property on the immobilized cells was dependent on the
      density of the immobilized cells on the functionalized PCL film. With the good
      cell-adhesive nature of gelatin and the efficient gene transfection on the dense
      immobilized cells, the incorporating the suitable of P(DMAEMA)/gelatin complexes
      onto PCL surfaces could endow the PCL substrates new and interesting properties
      for potential tissue engineering applications.

PMID- 21848339
TI  - One-pot microwave synthesis of water-dispersible, ultraphoto- and pH-stable, and
      highly fluorescent silicon quantum dots.
AB  - Fluorescent silicon quantum dots (SiQDs) are facilely prepared via one-pot
      microwave-assisted synthesis. The as-prepared SiQDs feature excellent aqueous
      dispersibility, robust photo- and pH-stability, strong fluorescence, and
      favorable biocompatibility. Experiments show the SiQDs are superbly suitable for
      long-term immunofluorescent cellular imaging. Our results provide a new and
      invaluable methodology for large-scale synthesis of high-quality SiQDs, which are
      promising for various optoelectronic and biological applications.

PMID- 21848340
TI  - Cancer selective metallocenedicarboxylates of the fungal cytotoxin illudin M.
AB  - The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and
      indiscriminately cytotoxic fungal metabolite illudin M (1) displayed
      antiproliferative activity at submicromolar IC(50) (72 h) values against a panel
      of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to
      nonmalignant human foreskin fibroblasts (HF). The analogous bis(illudinyl M) 1,1'
      ruthenocenedicarboxylate (2b) exhibited submicromolar IC(50) (72 h) values only
      against MDA-MB-231 and MCF-7/Topo breast carcinoma and HL-60 leukemia cells.
      Cytotoxicity studies in the presence of inhibitors of c-Jun N-terminal kinase
      (JNK) or extracellular signal-regulated kinase (ERK) revealed that the high
      efficacy of 2a, but not that of 2b, against HCT-116 colon cancer cells depends on
      active JNK/ERK signaling. A new illudin M lactone 5 was of low anticancer
      activity, but its ruthenocene diester 6b also reached single-digit micromolar
      IC(50) (72 h) values in HCT-116, MCF-7, and HL-60 leukemia cells while not
      affecting HF. Compounds 2a and 6b were tolerated by mice symptom-free at single
      doses as high as 25 mg/kg body weight, which is evidence for them being
      chemically stable under physiological conditions. Compound 2a displayed a
      manageable in vivo toxicity profile when given repeatedly in high doses.

PMID- 21848341
TI  - Imaging multiple conductance states in an alamethicin pore.
AB  - Alamethicin is the archetypal antimicrobial pore-forming peptide. Although the
      peptide has long been known to form pores of characteristic conductances in lipid
      membranes, the precise nature of these pores is not known. Simultaneous calcium
      flux imaging and single-channel recording in a droplet interface bilayer allowed
      us to directly attribute multiple conductance states to a single point diffusing
      in the bilayer.

PMID- 21848342
TI  - Improving similarity-driven library design: customized matching and
      regioselective feature trees.
AB  - Reduced graph descriptors, like feature trees, are frequently applied in cases
      where the relative arrangement of functional groups is more important than exact
      substructure matches. Due to their ability to deal with fragmented molecules,
      they are well-suited for fragment space search and library design. We recently
      presented LoFT, a novel focused library design approach based on feature trees.
      During evaluation two drawbacks of the reduced graph descriptor were discovered:
      First, regioisomeric substructures cannot be distinguished in feature tree
      mappings which results in a large information loss especially when connecting R
      groups to cores. Second, the automatic matching procedure might result in
      undesired alignments, since the knowledge on what is considered as core by the
      user is not taken into account. In the following, we will present two approaches
      to overcome those drawbacks. The generation of the feature trees is modified, so
      that different arene substitution patterns can be recognized and a customized
      matching is introduced, allowing the user to determine the parts of the query,
      where the reagents are allowed to match. Subsequently we investigate the
      improvements on library design by reviewing the design scenarios which were
      already used for the evaluation of LoFT.

PMID- 21848343
TI  - Semiempirical UNO-CAS and UNO-CI: method and applications in nanoelectronics.
AB  - Unrestricted Natural Orbital-Complete Active Space Configuration Interaction,
      abbreviated as UNO-CAS, has been implemented for NDDO-based semiempirical
      molecular-orbital (MO) theory. A computationally more economic technique, UNO
      CIS, in which we use a configuration interaction (CI) calculation with only
      single excitations (CIS) to calculate excited states, has also been implemented
      and tested. The class of techniques in which unrestricted natural orbitals (UNOs)
      are used as the reference for CI calculations is denoted UNO-CI. Semiempirical
      UNO-CI gives good results for the optical band gaps of organic semiconductors
      such as polyynes and polyacenes, which are promising materials for
      nanoelectronics. The results of these semiempirical UNO-CI techniques are
      generally in better agreement with experiment than those obtained with the
      corresponding conventional semiempirical CI methods and comparable to or better
      than those obtained with far more computationally expensive methods such as time
      dependent density-functional theory. We also show that symmetry breaking in
      semiempirical UHF calculations is very useful for predicting the diradical
      character of organic compounds in the singlet spin state.

PMID- 21848344
TI  - Classical valence bond approach by modern methods.

PMID- 21848346
TI  - One-step hydrothermal synthesis of mesoporous anatase TiO2 microsphere and
      interfacial control for enhanced lithium storage performance.
AB  - Mesoporous TiO(2) anatase microspheres consisting of self-assembled nanocrystals
      have been synthesized by a one-step hydrothermal method at 120 (o)C using
      titanium-peroxo complex, without a post-calcination process. Transmission and
      scanning electron microscopic imaging reveal that diamond-shaped nanocrystals as
      primary particles, which are 20 nm in average width and 50 nm in length and
      oriented with (101) plane of anatase phase, are aggregated to form a secondary
      microsphere particle with 0.5-1 MUm in diameter. BET analysis data show that the
      TiO(2) anatase particles possess significantly large surface area of 254 m(2) g(
      1) with the pore size of ~14 nm. Mesoporous TiO(2) anatase anode shows an
      enhanced lithium storage performance in pyrrolidinium-based ionic liquid
      electrolyte diluted with ethyl methyl carbonate, delivering 195 - 150 mAhg(-1) at
      the C/2 rate with 77 % capacity retention and 98-99 % Coulombic efficiencies over
      50 cycles despite the absence of surface carbon-coating. AC impedance analysis
      results reveal that the formation of a stable solid electrolyte interphase (SEI)
      layer in diluted ionic liquid electrolyte induces the enhanced cycling
      performance. Control of electrode-electrolyte interfacial compatibility enables
      the enhancement of cycling performance and the preservation of microstructure.
      The data contribute to provide cost-efficient synthetic method for the TiO(2) and
      the interfacial control aspect of performance control for safer batteries.

PMID- 21848347
TI  - Reactivity of N-(1,2,4-triazolyl)-substituted 1,2,3-triazoles.
AB  - Synthetically useful rhodium(II) carbenes were obtained from N-(1,2,4-triazolyl)
      substituted 1,2,3-triazoles and Rh(II) carboxylates. The electron-withdrawing
      1,2,4-triazolyl group reveals the heretofore unknown reactivity of nonsulfonyl
      1,2,3-triazoles, which exhibit the reactivity of diazo compounds. The resulting
      carbenes provide ready asymmetric access to secondary homoaminocyclopropanes (80
      95% ee, dr >20:1) via reactions with olefins and also engage in efficient
      transannulation reactions with nitriles.

PMID- 21848348
TI  - Environmentally safe health care agencies: nursing's responsibility,
      Nightingale's Legacy.
AB  - Florence Nightingale and subsequent nurse scholars have written about the impact
      of the environment on human health. Nightingale described, and staked out, the
      nurse's role in optimizing environments for healing. Since Nightingale's time
      numerous scholars have documented that environmental conditions play a major role
      in the health of individuals and populations. As nurses become more informed
      about the environment as a determinant of human health, they will be able to
      advocate more effectively for environmental conditions that promote health. This
      article provides both theoretical and practical perspectives to integrate
      environmental concerns into nursing practice. It recommends specific actions
      nurses can undertake to improve the environment within the health care setting.
      In particular the article provides a historical review of an environmental focus
      in nursing, discusses ways to manage both upstream waste and downstream waste
      (solid, biohazard, and hazardous chemical wastes) so as to decrease environmental
      pollution, and recommends specific nursing actions to promote a healthy
      environment within our health care agencies.

PMID- 21848349
TI  - Healthy buildings: impact on nurses and nursing practice.
AB  - Mounting evidence indicates that buildings can be a significant cause of human
      illness and environmental degradation. According to the United States (US)
      Environmental Protection Agency, indoor air pollution is one of the top five
      environmental risks to public health in the US. This may be related, to a large
      extent, to the fact that US citizens spend as much as 95% of their time indoors.
      Health care leaders, designers, and architects, recognizing the connection
      between health and the buildings in which much time is spent, are engaging in
      sustainable design and construction for healthy, 'green' buildings. The purpose
      of this article is to assist nurses in understanding the impact that unhealthy
      buildings can have on nurses and nursing practice and to provide tools and
      resources to assist nurses in transforming the health care industry with the goal
      of creating healing environments and reducing the negative environmental impact
      of the health care industry. First definitions, current initiatives, and
      motivations related to sustainable designs will be presented. Next sustainable
      health care design strategies, such as site planning, clean transportation, water
      conservation, healthy materials selection, indoor environmental quality, and also
      the benefits of sustainable design will be discussed. The article will conclude
      by sharing a variety of resources nurses can use to create healing environments
      in health care settings.

PMID- 21848350
TI  - Healthy choices: transforming our hospitals into environmentally healthy and safe
      places.
AB  - While it is commonly understood that the quality of the air we breath and the
      water we drink can impact our health, it is often more difficult to recognize
      that our choices of the health care products, along with the way we dispose of
      them, and the chemicals we spray on our foods or use to clean and disinfect may
      actually compromise the environment and consequently our health. This article
      will guide nurses and other health care professionals as they transform our
      hospitals into environmentally healthy and safe places by helping them adhere to
      environmentally preferable purchasing policies, follow environmentally conscious
      waste management strategies, decrease use of chemical pollutants, promote use of
      healthy foods, and provide leadership in environmental stewardship.

PMID- 21848345
TI  - Isoprostane generation and function.

PMID- 21848351
TI  - Home environmental health risks.
AB  - Home environmental health risks and the pollution of indoor residential air are
      becoming increasingly recognized as sources of injury and exacerbation of
      illness, particularly in vulnerable populations such as pregnant women, infants,
      children, the elderly, and those living with a chronic medical condition or
      disability. Nurses play a key role in prevention, education, and screening
      activities for patients. Core environmental health knowledge is essential for all
      nurses regardless of setting or population of practice. This article provides a
      review of the literature of five common home environmental health risks: lead,
      carbon monoxide, radon, pesticides, and the broad chemical category of volatile
      organic compounds. Particular emphasis is placed on the review of articles that
      address low-dose exposures, such as those most commonly found in the residential
      environment. Current standards of practice regarding risk minimizations are
      discussed, and nationally recognized preventative action steps and environmental
      health resources are presented.

PMID- 21848352
TI  - Global warming: a public health concern.
AB  - Over the last 100 years the average temperature on the Earth has risen
      approximately 1oFahrenheit (F), increasing at a rate twice as fast as has been
      noted for any period in the last 1,000 years. The Arctic ice cap is shrinking,
      glaciers are melting, and the Arctic permafrost is thawing. There is mounting
      evidence that these global climate changes are already affecting human health.
      This article provides a brief overview of global warming and climate changes,
      discusses effects of climate change on health, considers the factors which
      contribute to climate changes, and reviews individual and collective efforts
      related to reducing global warming.

PMID- 21848353
TI  - Regulatory, institutional, and market-based approaches towards achieving
      comprehensive chemical policy reform.
AB  - The purpose of this article is to inform nurses and other health care
      professionals about the nexus between the environment and health and present
      approaches in which they can be involved so as to support comprehensive reform of
      chemicals management in the United States. It discusses the health impact of
      hazardous chemicals and the environmental regulatory failures within the U.S. to
      protect the public. It also reports on international chemical management
      initiatives and key elements of chemical policy reform that can guide the U.S.
      regulatory, market-based, and institutional-based approaches to a comprehensive,
      chemical policy reform. The role of nursing in advocating for these reforms will
      be presented.

PMID- 21848354
TI  - Survey of advanced practice registered nurses disciplinary action.
AB  - The nursing profession continues to struggle to find the most appropriate
      approach to credentialing Advanced Practice Registered Nurses (APRNs). One early
      step in addressing this struggle is determining the incidence of APRN
      disciplinary actions by boards of nursing. This article presents data from 2003
      and 2004 describing the incidence of APRN disciplinary actions by United States
      boards of nursing. Fifty-one boards of nursing, all members of the National
      Council of State Boards of Nursing, were asked to report the numbers of APRN
      discipline cases for 2003 and 2004 which had been resolved, using a tool that
      differentiated disciplinary cases into four data categories: chemical impairment,
      exceeding scope of practice, unprofessional conduct, and safety or abuse of
      patients. Thirty-eight (74.5%) of 51 boards of nursing reported discipline data
      for a total of 125,882 APRNs showing 688 disciplinary actions were taken during
      2003 and 2004. This indicates that APRNs experience a low incidence of discipline
      related to chemical impairment, exceeding scope of practice, unprofessional
      conduct, and safety or abuse of patients.

PMID- 21848355
TI  - Measuring fall program outcomes.
AB  - Nurses help to ensure patient safety, which includes preventing falls and fall
      related injuries. The aging Veteran population, like the general population, is
      at risk for falls and fall related injuries whether at home, in hospitals or in
      long term care facilities. Nurses are leading practice innovations to
      systematically assess patients' risk for falls and implement population based
      prevention interventions. To determine the effectiveness of programs, data can be
      analyzed using a variety of statistical measures to determine program impacts.
      Thus, data analysis of fall rates by type of fall and severity of fall related
      injury can help facilities examine the effectiveness of their interventions and
      program outcomes. Examples of actual fall prevention programs and their
      approaches to measurement are showcased in this article.

PMID- 21848356
TI  - Moving from tradition to evidence: a review of psychiatric nursing intervention
      studies.
AB  - This state-of-the-evidence review summarizes characteristics of intervention
      studies published from January 2000 through December 2005 in five psychiatric
      nursing journals. Intervention studies were defined as those evaluating the
      application of nursing strategies/procedures/practices for enhancing/promoting
      health or preventing disability/dysfunction. Of 486 research studies published in
      those journals, 77 were intervention studies, including 77% conducted in the
      United States. Interventions reflected psychological (57%), social (9%), and
      biological (12%) dimensions of the biopsychosocial model; 22% of the studies
      tested interventions with overlapping dimensions. Some studies included persons
      of various ages; however, 7 focused on adolescents, 36 on adults, and 10 on
      elders; 2 included children. The findings describe the current state of published
      intervention research in five psychiatric nursing journals and suggest the need
      for increased dissemination of intervention research, more rigorous testing of
      interventions, and more focused programs of research to build evidence for
      effective psychiatric nursing interventions across the lifespan and globally.

PMID- 21848357
TI  - Legislative: shortage of nurses: the school nursing experience.

PMID- 21848358
TI  - Causes and circumstances of death in a district hospital in northern Cameroon,
      1993-2009.
AB  - INTRODUCTION: In Sub-Saharan Africa (SSA) sound planning is required as interest
      increases in the decentralization of healthcare financing and the implementation
      of a sector-wide approach to health care. For this, improved knowledge of
      national morbidity and mortality is essential. Data from remote areas of SSA are
      needed to ensure that public health priority-setting and actions reflect the
      situation in all regions, not just those easily accessed and readily researched.
      In order to understand the causes, circumstances and changes over time of death
      in a remote and underserved region, this study sought information on all deaths
      in a district hospital over a 17 year period. METHODS: The study design was a
      retrospective review of the hospital records (in registers) of all patients
      hospitalized in Kolofata District Hospital, a rural public hospital in the Far
      North Region of Cameroon, 1 January 1993 to 31 December 2009. A line listing was
      extracted of all 1281 inpatient deaths, and this included dates of admission and
      death; patient name, address, sex and ethnic group; presenting complaint;
      duration of symptoms; summary of physical examination; and the diagnosis presumed
      to be the cause of death. RESULTS: Children under the age of 15 years and males
      comprised the majority of deaths (63.9% and 56.0%, respectively). Causes of death
      were related to the seasons. Infectious diseases including acute lower
      respiratory tract infection, malaria and diarrhoeal diseases were the leading
      causes of death; AIDS caused most adult deaths. A total of 67% of patients
      presented within 1 week of symptom onset, and 56.8% of deaths occurred on or
      before the day after admission. Deaths due to AIDS, malaria and complications of
      pregnancy increased over time. Among Kolofata District residents, death from
      vaccine-preventable measles and neonatal tetanus were rare, particularly in the
      later study years. The proportion of deaths attributed to non-communicable
      diseases did not increase in the 17 year period. CONCLUSIONS: To reduce mortality
      in this world region, priority should be given to the prevention and management
      of lower respiratory tract infections, malaria, diarrhoeal diseases, AIDS, and
      the complications of pregnancy. The planning of health resources and activities
      should take into account seasonal variations in the causes of death. Improvements
      to emergency services and community education that emphasises the need for
      earlier presentation when ill should reduce deaths that occur soon after hospital
      admission. Death due to measles and neonatal tetanus has become rare, a
      reflection of the effectiveness in this area of the national vaccination program.

PMID- 21848359
TI  - Unmet psychological and practical needs of patients with cancer in rural and
      remote areas of Western Australia.
AB  - INTRODUCTION: The financial and psychological impacts of cancer treatment on
      patients can be severe. Practical issues, such as childcare, medical supplies and
      obtaining 'home help' can impose financial strain on patients and their families,
      and this is often exacerbated by a simultaneous loss of income if a patient is
      unable to continue employment during treatment, or if family members become full
      time carers. These financial difficulties are often more severe for patients from
      rural regions because cancer services tend to be concentrated in metropolitan
      areas, requiring rural patients to relocate or undertake lengthy, frequent
      commutes to access treatment. The needs of rural cancer patients may differ from
      and exceed those of metropolitan cancer patients. Because of this, it is
      important to assess the needs of rural and metropolitan populations to develop
      appropriate, tailored supportive-care interventions. This article compares the
      unmet supportive-care needs of rural/remote with metropolitan cancer patients in
      Western Australia (WA), a large and sparsely populated Australian state with a
      substantial rural and remote population. This article is part of a larger program
      of research assessing the supportive-care needs of WA cancer patients. METHODS:
      Participants were identified through the Western Australian Cancer Registry
      (WACR) and considered eligible if diagnosed with any type of cancer between 6
      months and 2 years previously. A random sample of 2079 potential participants was
      generated, structured to include all cancer types and geographical areas, and
      with both sexes randomised within these groups. Following confirmation and
      exclusion of deceased patients and those patients excluded at the treating
      doctor's request, 1770 patients were contacted. Participants were asked to
      complete a demographic questionnaire and the Supportive Care Needs Survey Long
      Form (SCNS-59). Data from participants who completed and returned both
      questionnaires were analysed using descriptive statistics and chi(2) tests; and
      any missing data were addressed through imputation. RESULTS: Eight hundred and
      twenty-nine participants (47% response) completed the SCNS-LF59 and 786 (94.8%)
      completed both questionnaires. Of the 786 respondents, 234 (30%) were from rural
      areas and 169 (22%) were from remote areas. Among the 15 items with the highest
      frequency for 'some needs' on the survey, participant needs did not vary by
      geographical location, with no significant differences found for any of the 15
      items. The item for which the greatest, albeit non-significant (p = 0.12)
      difference was seen, was 'concern about financial situation'. The differences
      among all other items were not significant (p-values from 0.28 to 0.96).
      Furthermore, the proportion of participants reporting 'moderate to high need' on
      these items also did not differ significantly across geographical populations (p
      values from 0.13 to 0.91). CONCLUSIONS: The lack of discrepancy between rural,
      remote and metropolitan cancer patients' unmet needs provides a positive message
      regarding the state of WA cancer services and the level of support provided to
      rural and remote WA residents. Future research should also assess the unmet needs
      of rural and remote carers and families in comparison with metropolitan carers
      and families, to ensure that services are well-equipped to meet the needs of all
      individuals involved in a patient's cancer journey.

PMID- 21848360
TI  - Comparative assessment of dental arch relationships using Goslon Yardstick in
      patients with unilateral complete cleft lip and palate using dental casts, two
      dimensional photos, and three-dimensional images.
AB  - OBJECTIVE: Comparison of the use of two-dimensional (2D) and three-dimensional
      (3D) images for rating dental arch relationships. MATERIALS AND METHODS: The
      sample consists of pretreatment dental casts, 2D photographs, and 3D images of 70
      patients with unilateral complete cleft lip and palate. Two experienced examiners
      used the Goslon Yardstick to rate dental arch relationships. The ratings were
      done three times for all groups. Weighted kappa statistics were used to evaluate
      intra- and interrater agreement and the agreement between the groups. RESULTS:
      Intra- and interexaminer agreement were high for all groups (between 0.86 and
      0.96), indicating very good reproducibility. The mean Goslon scores ranged
      between 2.84 and 2.90. CONCLUSION: 2D and 3D imaging of dental casts provides a
      valid alternative for actual study models for rating dental arch relationships.

PMID- 21848361
TI  - Treatment of extranodal marginal zone lymphoma of mucosa-associated lymphoid
      tissue with fludarabine: effect on tumor microenvironment.
AB  - Gastric Helicobacter pylori (HP) positive extranodal marginal zone lymphoma of
      mucosa-associated lymphoid tissue (MALT) develops during chronic antigenic
      stimulation with specific T-cell help. Chemotherapy that acts both on the
      malignant B-cells and on T-cells in the microenvironment, i.e. nucleoside
      analogs, might therefore be an attractive treatment. In 14 patients with gastric
      MALT lymphoma treated with fludarabine, alterations in T-cell subsets were
      studied in subsequent peripheral blood samples and in gastric biopsies. Treatment
      with fludarabine resulted in a steep decrease in T-cell subsets in peripheral
      blood samples. By contrast no decrease in T-cell populations was observed in
      subsequent gastric biopsy samples and a moderate increase was observed in
      relative infiltration with CD3 +, CD4 + and CD8 + cells. In addition an increase
      in density of FOXP3 + cells (i.e. Tregs) was seen (p = 0.047). These alterations
      in different T-cell subsets were not observed in gastric biopsy samples of
      patients treated with HP-eradication only.

PMID- 21848362
TI  - Molecular cytogenetics studies reveal unexpected chromosomal inversion as variant
      of t(12;21)(p13;q22) in child with B-cell precursor acute lymphoblastic leukemia.

PMID- 21848363
TI  - Low dose palliative radiotherapy for splenomegaly in hematologic disorders.
AB  - Splenomegaly (SM) is a common complication in hematologic disorders often
      associated with hypersplenism, and may cause pain, epigastric discomfort and
      variable systemic effects due to cytopenias. We retrospectively evaluated the
      results of palliative splenic irradiation (PSI) in terms of symptomatic relief in
      patients with hematologic disorders. In 1998-2006, 32 patients with hematologic
      disorders (median age 57) received 52 courses of PSI for SM. Twenty-one patients
      (66%) were diagnosed with myeloproliferative disorders (MPD), five patients (16%)
      had malignant lymphoma (ML), five patients (16%) had chronic lymphocytic leukemia
      (CLL) and one patient (3%) had hairy cell leukemia. Splenomegaly was accompanied
      by pain, anemia, thrombocytopenia and cachexia. Radiation therapy to the entire
      spleen was delivered by two parallel opposed fields using 0.5 Gy daily fractions
      given 5 days per week to a total dose of 6-10 Gy. PSI resulted in splenic size
      reduction in 78.8%, improvement of anemia in 75% and improvement of
      thrombocytopenia in 63.5% of PSI courses. The median survival (MS) of patients
      with MPD, CLL and ML was 45, 10 and 5 months, respectively. The MS of responders
      to PSI versus non-responders was 45 and 16 months, respectively (hazard ratio
      0.17; p = 0.03; 95% confidence interval 0.035-0.84). In our hands, low dose PSI
      provided effective palliation for patients with hematologic disorders with SM.
      Splenic re-irradiation was feasible without excessive toxicity.

PMID- 21848367
TI  - Structural abnormalities of the central auditory pathway in infants with
      nonsyndromic cleft lip and/or palate.
AB  - OBJECTIVE: To investigate possible structural abnormalities of the central
      auditory pathway in infants with nonsyndromic cleft lip and/or palate (NSCL/P).
      PARTICIPANTS: Twenty-seven Chinese infants with NSCL/P, aged from 6 to 24 months.
      INTERVENTION: Morphological magnetic resonance imaging (MRI) measurements of the
      central auditory nervous system (CANS) in infants with NSCL/P were analyzed and
      compared with those of age- and sex-matched normal controls. RESULTS: No
      significant group differences were found in general brain measurements, including
      volumes of the brain stem and right hemisphere. However, infants with NSCL/P had
      statistically significantly smaller volumes of the left thalamus and left
      auditory cortex and notably decreased thickness of the left auditory cortex.
      CONCLUSION: Cortical abnormalities were more marked compared with other MRI
      measurements. Structural CANS abnormalities in infants with NSCL/P may be located
      mainly in the left cerebral hemisphere. The development and maturation of the
      auditory cortex in infants with NSCL/P may be abnormal when compared with those
      of normal children.

PMID- 21848366
TI  - Expression of functional TRPA1 receptor on human lung fibroblast and epithelial
      cells.
AB  - The transient receptor potential subfamily A member 1 (TRPA1) is a non-selective
      cation channel implicated in the pathogenesis of several airway diseases like
      asthma and chronic obstructive pulmonary disease (COPD). Most of the research on
      TRPA1 focuses on its expression and function in neuronal context; studies
      investigating non-neuronal expression of TRPA1 are lacking. In the present study,
      we show functional expression of TRPA1 in human lung fibroblast cells (CCD19-Lu)
      and human pulmonary alveolar epithelial cell line (A549). We demonstrate TRPA1
      expression at both mRNA and protein levels in these cell types. TRPA1 selective
      agonists like allyl isothiocyanate (AITC), 4-hydroxynonenal (4-HNE),
      crotonaldehyde and zinc, induced a concentration-dependent increase in Ca+2
      influx in CCD19-Lu and A549 cells. AITC-induced Ca+2 influx was inhibited by
      Ruthenium red (RR), a TRP channel pore blocker, and by GRC 17536, a TRPA1
      specific antagonist. Furthermore, we also provide evidence that activation of the
      TRPA1 receptor by TRPA1 selective agonists promotes release of the chemokine IL-8
      in CCD19-Lu and A549 cells. The IL-8 release in response to TRPA1 agonists was
      attenuated by TRPA1 selective antagonists. In conclusion, we demonstrate here for
      the first time that TRPA1 is functionally expressed in cultured human lung
      fibroblast cells (CCD19-Lu) and human alveolar epithelial cell line (A549) and
      may have a potential role in modulating release of this important chemokine in
      inflamed airways.

PMID- 21848365
TI  - Alterations in regulatory T-cells: rediscovered pathways in immunotoxicology.
AB  - In addition to the effector T-cells subsets, T-cells can also differentiate into
      cells that play a suppressive or regulatory role in adaptive immune responses.
      The cell types currently identified as regulatory T-cells (T(regs)) include
      natural or thymic-derived T(regs), T-cells which express Foxp3(+)CD25(+)CD4(+)
      and can suppress immune responses to autoreactive T-cells, as well as inducible
      T(regs), that are generated from naive T-cells in the periphery after interaction
      with antigens presented by dendritic cells. Inducible T(regs) include T(H)3
      cells, T(r)1 cells, and Foxp3(+)-inducible T(regs). T(regs) have been shown to be
      critical in the maintenance of immune responses and T-cell homeostasis. These
      cells play an important role in suppressing responses to self-antigens and in
      controlling inappropriate responses to non-self-antigens, such as commensal
      bacteria or food in the gut. For example, depletion of CD4(+)CD25(+) T(regs) from
      mice resulted in the development of multi-organ autoimmune diseases.
      CD4(+)CD25(+) T(regs) and/or IL-10-producing T(r)1 cells are capable of
      suppressing or attenuating T(H)2 responses to allergens. Moreover, adoptive
      transfer of CD4(+)CD25(+) T(regs) from healthy to diseased animals resulted in
      the prevention or cure of certain autoimmune diseases, and was able to induce
      transplantation tolerance. Clinical improvement seen after allergen immunotherapy
      for allergic diseases such as rhinitis and asthma is associated with the
      induction of IL-10- and TGFbeta-producing T(r)1 cells as well as FoxP3-expressing
      IL-10 T-cells, with resulting suppression of the T(H)2 cytokine milieu.
      Activation, expansion, or suppression of CD4(+)CD25(+) T(regs) in vivo by
      xenobiotics, including drugs, may therefore represent a relevant mechanism
      underlying immunotoxicity, including immunosuppression, allergic asthma, and
      autoimmune diseases.

PMID- 21848368
TI  - Evaluation of the INNOVANCE PFA P2Y test cartridge: sensitivity to P2Y(12)
      blockade and influence of anticoagulant.
AB  - Monitoring of platelet ADP receptor P2Y(12) inhibition may be performed by a
      variety of platelet function assays. Given the lack of sensitivity of the
      existing PFA-100(r) cartridge formulations to detect P2Y(12) inhibition, a new
      cartridge for the PFA-100 (INNOVANCE(r) PFA P2Y) has recently been developed. The
      performance of the new PFA-100 test cartridge was compared with standard
      collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges, light
      transmission aggregometry, vasodilator-stimulated phosphoprotein, the
      VerifyNow(r) P2Y(12) assay and multiple electrode aggregometry. In this study, 20
      normal blood samples anticoagulated with either citrate or hirudin were spiked
      with two different clinically relevant concentrations (1 and 10 uM final
      concentration) of the prasugrel active metabolite (R-138727, Lilly/Daiichi
      Sankyo) for 30 min at 37 degrees C. Comparison of the platelet function tests
      demonstrated that all tests (except CADP and CEPI) were substantially inhibited
      by 10 uM R-138727. Intermediate results were typically obtained with 1 uM R
      138727 in citrated blood. However, both MEA ADP and ADPHS tests were highly
      sensitive to 1 uM R-138727 in hirudin anticoagulated blood. Further comparison of
      citrate or hirudin blood samples (N = 5) revealed that all platelet tests (except
      CEPI) became more sensitive to 1 uM R-138727 in hirudinized blood. The INNOVANCE
      PFA P2Y cartridge proved to be sensitive to P2Y(12) inhibition and was comparable
      to other currently available platelet function tests. The sensitivity of all
      platelet function tests for detecting in vitro inhibition of P2Y(12) is markedly
      different depending on the anticoagulant used.

PMID- 21848364
TI  - HIV type 1 Gag as a target for antiviral therapy.
AB  - The Gag proteins of HIV-1 are central players in virus particle assembly,
      release, and maturation, and also function in the establishment of a productive
      infection. Despite their importance throughout the replication cycle, there are
      currently no approved antiretroviral therapies that target the Gag precursor
      protein or any of the mature Gag proteins. Recent progress in understanding the
      structural and cell biology of HIV-1 Gag function has revealed a number of
      potential Gag-related targets for possible therapeutic intervention. In this
      review, we summarize our current understanding of HIV-1 Gag and suggest some
      approaches for the development of novel antiretroviral agents that target Gag.

PMID- 21848369
TI  - The value of microbiological screening in cleft lip and palate surgery.
AB  - OBJECTIVE: This study was performed to investigate whether nasal and
      oropharyngeal microbiological swabs taken prior to cleft lip and palate surgery
      correlated with the oronasal flora at the time of surgery and whether specific
      culture results affected surgical outcome. METHODS: Prospective audit set in two
      designated U.K. cleft centers each with a single surgeon. Nasal and oropharyngeal
      microbiological swabs were taken within 2 weeks prior to surgery and again on the
      operating table. Adverse outcome measures included postoperative pyrexia, wound
      dehiscence, or fistula formation. RESULTS: One hundred forty-four cases were
      recruited over 12 months. Nasal swabs cultured organisms significantly more often
      than oropharyngeal swabs (p < .0001). No significant difference was detected in
      the number of cases with a positive microbiology culture preoperatively compared
      with perioperative sampling (48% and 50%). The specific organisms cultured from
      preoperative swabs were the same as those cultured at surgery in only half of
      cases. Preoperative microbiology swabs were poorly predictive of the oronasal
      flora at surgery. Antibiotic treatment of patients with positive preoperative
      microbiology did not significantly reduce the incidence of bacterial colonization
      or significantly alter clinical outcome. CONCLUSION: Preoperative microbiological
      investigation is not helpful in predicting the nasal and oropharyngeal flora at
      the time of surgery. Further, culture results did not correlate with
      postoperative outcome, regardless of whether pre- or perioperative antibiotic
      therapy was instigated. This evidence suggests that microbiology screening swabs
      are an unnecessary investigation.

PMID- 21848370
TI  - Separation and purification of ginsenoside Re from ginseng bud by selective
      adsorption of active carbon and preparative high-performance liquid
      chromatography.
AB  - Ginsenoside Re (G-Re) is a major ingredient of the ginseng bud. A novel and rapid
      method to isolate and purify G-Re from ginseng buds was established. The
      procedure involves solvent extraction of ginseng bud powder, then pre
      purification with an active carbon column and purification by preparative HPLC
      (prep-HPLC). Active carbon, which can selectively adsorb other kinds of
      ginsenosides except G-Re, was used as a new media to pre-purify G-Re in this
      study. In addition, we describe the development and optimisation of prep-HPLC
      parameters for G-Re purification. Compared to other types of high-purity G-Re
      preparation methods, this method is efficient, economical, waste-conscious and
      has the potential to maximise.

PMID- 21848371
TI  - Biopreservation of hamburgers by essential oil of Zataria multiflora.
AB  - Hamburgers with high nutrient supply and a loosely-packed structure present
      favourable conditions for microbial growth. In this study, the chemical
      composition and antimicrobial activity of the essential oil of Zataria multiflora
      and its potential application as a natural preservative in reducing the
      indigenous microbial population of hamburgers were investigated. Carvacrol,
      thymol and linalool were found to be the most abundant constituents of the
      essential oil using GC-MS analysis. The essential oil exhibited strong
      antibacterial activity against Gram-positive and Gram-negative bacteria. Addition
      of Z. multiflora essential oil in concentrations higher than MIC values
      influenced the microbial population of hamburgers stored at 25 degrees C, 4
      degrees C and -12 degrees C. The significant results of this study are our
      observations that the use of Z. multiflora essential oil at 0.05% v/w increases
      the time needed for the natural microflora of hamburgers to reach concentrations
      able to produce a perceivable spoilage at refrigerator and room temperatures
      without any inverse effect on their sensory attributes. Freezing of essential oil
      treated hamburgers may also reduce the risk of diseases associated with
      consumption of under-cooked hamburgers through significant microbial reduction by
      more than 3 log.

PMID- 21848372
TI  - Reversal effects of traditional Chinese herbs on multidrug resistance in cancer
      cells.
AB  - Multidrug resistance (MDR) continues to be a major obstacle for successful
      anticancer therapy. In this work, fractions from 17 clinically used antitumour
      traditional Chinese medicinal herbs were tested for their potential to restore
      the sensitivity of MCF-7/ADR and A549/Taxol cells to a known antineoplastic
      agent. The effects of these fractions were evaluated by MTT method and an assay
      of the cellular accumulation of doxorubicin. Fractions from the PB group (herbs
      with the ability to promote blood circulation and remove blood stasis) showed
      more significant effects than fractions from the CH group (herbs with the ability
      to clear away heat and toxic materials). Fractions from CH2Cl2 extracts were more
      effective than fractions from EtOAc extracts. Five herbs (Curcuma wenyujin,
      Chrysanthemum indicum, Salvia chinensis, Ligusticum chuanxiong Hort. and Cassia
      tora L.) could sensitise these resistant cancer cells at a non-toxic
      concentration (10 ug mL-1), and markedly increased doxorubicin accumulation in
      MCF-7/ADR cells, which necessitates further investigations on the active
      ingredients of these herbs and their underlying mechanisms.

PMID- 21848373
TI  - Staff experience, knowledge and attitudes regarding the management of adolescent
      patients in adult mental health units.
AB  - OBJECTIVE: Inpatient psychiatric care of adolescents should, where possible, be
      provided in specialized units. However, admission of adolescent patients to adult
      mental health units does occur. There is a paucity of data about this practice.
      This study collates information about the experience, attitudes and knowledge of
      clinical staff regarding the care of adolescent patients in adult psychiatry
      units within Northern Sydney Central Coast Area Health Service (NSCCHS). METHOD:
      A survey was emailed to all clinical staff with employer accessible email
      addresses in NSCCHS. RESULTS: The response rate was 29% (n = 108). The majority
      of respondents believed their wards were "not at all" (30.7%) or "only a little"
      (57.4%) equipped to care for adolescent patients. The majority felt "moderately"
      (39.6%) or "very" (16.8%) confident to care for these patients; however, a
      significant proportion (43.2%) lacked confidence. There was no significant
      difference across the responses of psychiatrists, psychiatry registrars and
      nursing staff to these questions. The majority felt the objectives of these
      admissions were met "only a little" (47.4%) or "not at all" (16.5%). Many
      concerns regarding the admission of adolescents to adult wards were reported.
      CONCLUSIONS: Generally, staff were not in favour of admitting adolescent patients
      to adult mental health units apart from in exceptional circumstances. Staff
      harboured concerns about several aspects of care for adolescents in adult wards.

PMID- 21848377
TI  - A survey of the images used on the Arthritis Research UK (ARUK) Osteomalacia Mind
      Map in relation to cultural background.
AB  - OBJECTIVE: To explore the appropriateness of the images in the Arthritis Research
      UK Mind-Map for Osteomalacia with people for whom it was intended (Bengali;
      Gujarati; Hindi; Punjabi and Urdu). METHODS: Participants were identified in a
      convenient sample from contacts within their communities. They were asked to
      comment on the images for meaning, suitability and offence to people from their
      culture. A total of 56 people were surveyed. RESULTS: Appropriateness responses
      were either generic: Images of bone metabolism were confusing [31/56]; muscle
      weakness "looked like knee pain" [16/56]; a bending and cracking bone "looked
      like a dog's bone" [22/56] and that the bone pain man "looked like he had
      toothache" [21/56]; or culture-specific the depiction of food and the Burqa as
      below. Only 3 images caused any offence, phrased as "may offend someone". The
      Burqa was described as stereotyping. CONCLUSION: The images on the current
      Osteomalacia Mind-Map are largely appropriate and have little capacity to offend.
      Some may be improved upon in terms of conveying meaning. One set of images can
      suit all of the cultures. PRACTICE IMPLICATIONS: Images can cross cultural
      barriers. The revised Mind-Map should be more useful in conveying meaning to a
      wider selection of patients.

PMID- 21848378
TI  - Twenty-five years ago. 1986.

PMID- 21848380
TI  - Lipoma - a case study.

PMID- 21848381
TI  - Operating theatre photography for orthopaedics and aesthetic surgery.
AB  - The aim of this paper is to examine the author's personal experience and practice
      in operating theatre photography. The ways of working are personal to the author
      but hopefully will help others in undertaking this type of work.

PMID- 21848382
TI  - Writing up a case presentation.

PMID- 21848386
TI  - IMI Conference 2010 - the New Voices Experience.

PMID- 21848389
TI  - Through the keyhole.

PMID- 21848390
TI  - Unauthorised pregnancies and use of maternity care in rural China.
AB  - OBJECTIVES: To describe the use of maternity care in rural China by the legal
      status of the pregnancy. METHODS: Cross-sectional survey wherein information was
      obtained about 2576 women who gave birth in 2006. Logistic regression was used to
      compare women having an unauthorised pregnancy with those having an authorised
      second birth, adjusting for confounding factors. RESULTS: Almost all respondents
      had antenatal care and most deliveries occurred in hospitals. Women with
      unauthorised pregnancies were significantly less likely to have had maternity
      care, particularly prenatal care, postnatal care, to have been hospitalised
      during pregnancy, and to have been reimbursed for hospital delivery costs than
      women with an authorised second birth. They were also more likely to have been
      hospitalised for seven or more days after delivery. Primiparous women used
      maternity care services and received financial support more often than women with
      an authorised second birth. Among the women with an unauthorised pregnancy an
      important reason for not using hospital care during pregnancy or delivery was
      financial constraint. CONCLUSIONS: Women with unauthorised pregnancies use less
      maternity care, although pregnancy in such circumstances may adversely impact
      their health. Primiparous women benefit from more financial support than
      multiparous women.

PMID- 21848391
TI  - Female sterilisation in the United States.
AB  - Female sterilisation is a safe and effective form of permanent birth control. In
      the United States (US), it is still the second most commonly used form of
      contraception overall and is the most frequently used method among married women
      and among women over 30 years of age. Although several European countries have
      noted a sharp decline in the number of women electing tubal sterilisation in
      recent years, such trends have not been as obvious in the US. While female
      sterilisation remains popular, there are considerable system-level barriers to
      getting the procedure for certain segments of the population as well as emerging
      concerns about appropriate utilisation of this contraceptive method in light of
      newer, reversible options and the knowledge that regret after permanent
      contraception is high. Given the complexity of this decision-making process, it
      is critical that providers ensure at the very least that women are aware of the
      potential disadvantages of tubal occlusion and are knowledgeable of other highly
      effective contraceptive methods that are available but vastly underutilised in
      the US, namely, vasectomy, intrauterine contraceptives, and implants.

PMID- 21848392
TI  - Macrophage migration-inhibitory factor is elevated in pregnant women with
      gestational diabetes mellitus.
AB  - OBJECTIVE: In reports, abnormal macrophage migration-inhibitory factor (MIF)
      production has been associated with several diseases. Furthermore, despite scarce
      data, increasing evidence suggest that MIF plays a central role in glucose
      homeostasis and in the development of type 1 and type 2 diabetes. However, serum
      MIF levels in gestational diabetes mellitus (GDM) have not yet been investigated.
      To address this question, we performed a prospective study between a group of
      pregnant women with GDM and healthy pregnant controls. MATERIALS AND METHODS: GDM
      group consisted of 43 pregnant women, whereas the control group consisted of 40
      healthy pregnant women. In the morning after an overnight fast, venous blood was
      sampled for the measurement of serum concentrations of insulin and MIF. Serum was
      separated by centrifugation and immediately stored at -80 degrees C until the
      assay. RESULTS: There was no significant difference between the groups for
      maternal characteristics. Women with GDM had significantly higher levels of serum
      insulin (14.37 +/- 9.92 uU/ml vs. 8.78 +/- 4.35 uU/ml; p = 0.001) and serum MIF
      concentrations (11.31 +/- 4.92 ng/ml vs. 5.31 +/- 4.07 ng/ml; p < 0.001) when
      compared with healthy pregnant control group. CONCLUSION: Our data demonstrated
      that serum levels of MIF are significantly elevated in patients with GDM. Our
      findings indicate that MIF might have a role in GDM; however, there is a need for
      further investigation.

PMID- 21848393
TI  - Male-mediated F1 effects in mice exposed to nonylphenol or to a combination of X
      rays and nonylphenol.
AB  - Nonylphenol (NP) is an environmental chemical with estrogenic activity. Exposure
      of the general population to radiation and NP is, very often, unavoidable because
      of the presence of both agents in the environment of human life and work. The aim
      of the study was to investigate the effect of subchronic 8-week exposure to NP
      alone or in combination with X-rays on sperm quantity and quality and on the
      possibility of the transmission of mutations induced in germ cells to the next
      generation. Eight-week exposure to NP and X-ray/NP combination diminished sperm
      count and increased the percent of abnormal spermatozoa, as well as having
      increased DNA damage in gametes. Some of those effects remained up to 8 weeks
      after the end of exposure. The exposure of males to 50 mg/kg body weight (b.w.)
      of NP and to 0.05 Gy + 25 mg/kg b.w. NP daily significantly decreased the percent
      of pregnant females. The fertilization ability of male mice was not diminished.
      Combined exposure to low doses of both agents significantly increased the mean
      number of dead implantations per pregnant female and the percentage of skeletal
      malformations. Results showed that mutations induced in germ cells by subchronic
      exposure to NP and to combined X-ray/NP exposure may be transmitted to the F1
      generation via sperm.

PMID- 21848394
TI  - Effects of prior vegetative growth, inoculum density, light, and mating on
      conidiation of Erysiphe necator.
AB  - Initiation of asexual sporulation in powdery mildews is preceded by a period of
      superficial vegetative growth of mildew colonies. We found evidence of a quorum
      sensing signal in Erysiphe necator that was promulgated at the colony center and
      stimulated conidiation throughout the colony. Removal of the colony center after
      putative signal promulgation had no impact upon timing of sporulation by 48-h-old
      hyphae at the colony margin. However, removal of the colony center before
      signaling nearly doubled the latent period. A relationship between inoculum
      density and latent period was also observed, with latent period decreasing as the
      number of conidia deposited per square millimeter was increased. The effect was
      most pronounced at the lowest inoculum densities, with little decrease of the
      latent period as the density of inoculation increased above 10 spores/mm.
      Furthermore, light was shown to be necessary to initiate conidiation of
      sporulation-competent colonies. When plants were inoculated and maintained in a
      day-and-night cycle for 36 h but subjected to darkness after 36 h, colonies kept
      in darkness failed to sporulate for several days after plants kept in light had
      sporulated. Once returned to light, the dark-suppression was immediately
      reversed, and sporulation commenced within 12 h. Merging of colonies of
      compatible mating types resulted in near-cessation of sporulation, both in the
      region of merging and in more distant parts of the colonies. Colonies continued
      to expand but stopped producing new conidiophores once pairing of compatible
      mating types had occurred, and extant conidiophores stopped producing new
      conidia. Therefore, in addition to a quorum-sensing signal to initiate
      conidiation, there appears to be either signal repression or another signal that
      causes conidiation to cease once pairing has occurred and the pathogen has
      initiated the ascigerous stage for overwintering.

PMID- 21848395
TI  - Characteristics of the spread of apple proliferation by its vector Cacopsylla
      picta.
AB  - The distribution and natural phytoplasma infection of Cacopsylla picta were
      investigated during a long-term field survey between 2002 and 2009 in commercial
      and abandoned apple proliferation-infected orchards throughout Germany, northern
      Switzerland, and eastern France. Comparable population dynamics were described
      for the different sites whereas considerable variations in the absolute
      population densities were observed among the years. Individual polymerase chain
      reaction (PCR) testing revealed, for each year, a rather stable natural infection
      rate with ?Candidatus Phytoplasma mali? of ?10% for overwintered adults of C.
      picta. Both genders were equally highly infected although more females were
      caught. The overall male/female ratio was 1:1.5. No direct correlation was found
      between the infection status of the orchard and the infection rate of
      overwintered C. picta. No influence of agricultural practices was seen. However,
      a relationship between the incidence of the disease and the vector population
      density became evident on a regional scale. Successful transmission of ?Ca. P.
      mali? occurred each year with overwintered individuals as well as with new
      adults. The transmission efficiency varied among the years within 8 to 45% for
      overwintered adults and 2 to 20% for individuals of the new generation. The load
      of single C. picta with ?Ca. P. mali? was determined by quantitative real-time
      PCR. High phytoplasma titers were measured in overwintered adults already at
      their first appearance in the orchards after remigration from their overwintering
      hosts. Thus, the data indicate the transmission of the disease on a regional
      scale by remigrant adults of C. picta and at a local scale within the same season
      by emigrant adults which developed on infected plants.

PMID- 21848396
TI  - Variation for resistance to kernel infection and toxin accumulation in winter
      wheat infected with Fusarium graminearum.
AB  - Host resistance is the main way to control Fusarium head blight (FHB) in wheat.
      Despite improved levels of resistance to infection and spread in vegetative
      tissue, the toxin deoxynivalenol (DON) can still accumulate to unacceptable
      concentration levels. In this study, our objectives were to assess the genetic
      variation for resistance to kernel infection (RKI) and resistance to toxin
      accumulation (RTA) and their role in controlling DON. We collected spikes with
      different levels of visual symptoms from each of 32 wheat genotypes and at four
      environments and determined DON and fungal biomass (FB) from each sample. We
      assessed RKI by regressing FB on the level of visual symptoms and RTA by
      regressing DON on FB for each genotype. Significant genetic effects were found
      for RKI and RTA. Some genotypes consistently had low FB in their grain despite
      increasing visual symptoms suggesting RKI. Additionally, some genotypes
      consistently had low DON in their grain despite increasing FB levels suggesting a
      higher RTA in these genotypes. The variation for RKI and RTA explained a
      significant fraction of the variation for DON among genotypes with moderate
      visual symptoms using independent grain samples. Although RKI and RTA were
      significantly correlated (r = 0.58, P = 0.05), RTA was more predictive of DON
      accumulation because it modeled 32 to 44% of the genotype sum of squares for DON,
      while only 9 to 10% were predicted using RKI. Thus, variation for RTA was
      important in explaining variation for DON among genotypes with acceptable levels
      of resistance to fungal infection and spread. This work indicates that there is a
      need to develop a better understanding of RTA and rapid screening methods for
      this trait.

PMID- 21848397
TI  - Invasion genetics of the chestnut blight fungus Cryphonectria parasitica in
      Switzerland.
AB  - Cryphonectria parasitica is the best-known example of an invasive forest pathogen
      in Europe. In southern Switzerland, chestnut blight was first reported in 1948
      whereas, north of the Alps, it did not appear until the 1980s. Between 1995 and
      2008, we sampled 640 C. parasitica isolates from nine populations south of the
      Alps and nine north of the Alps. Twelve historical isolates, collected between
      1950 and 1972 in the south, were obtained from our collection. All 652 isolates
      were screened at 10 microsatellite loci to test for the existence of divergent
      genetic pools and to infer possible origins of haplotypes. In total, 52
      haplotypes were identified. Structure software analysis indicated that 43
      haplotypes (including all historical haplotypes) belonged to a main cluster, 6
      haplotypes belonged to a different cluster, and 3 haplotypes had an intermediate
      allele pattern. All newly founded populations in northern Switzerland were
      initiated by one or just a few haplotypes from the main cluster, which probably
      came directly from the populations south of the Alps. Subsequently, genetic
      diversity increased through mutations, sexual reproduction, or new migrations.
      The highest increase in diversity was observed in populations where haplotypes
      from different genetic pools were encountered.

PMID- 21848398
TI  - The biology of Frankia sp. strains in the post-genome era.
AB  - Progress in understanding symbiotic determinants involved in the N(2)-fixing
      actinorhizal plant symbioses has been slow but steady. Problems persist with
      studying the bacterial contributions to the symbiosis using traditional
      microbiological techniques. However, recent years have seen the emergence of
      several genomes from Frankia sp. strains and the development of techniques for
      manipulating plant gene expression. Approaches to understanding the bacterial
      side of the symbiosis have employed a range of techniques that reveal the
      proteomes and transcriptomes from both cultured and symbiotic frankiae. The
      picture beginning to emerge provides some perspective on the heterogeneity of
      frankial populations in both conditions. In general, frankial populations in root
      nodules seem to maintain a rather robust metabolism that includes nitrogen
      fixation and substantial biosynthesis and energy-generating pathways, along with
      a modified ammonium assimilation program. To date, particular bacterial genes
      have not been implicated in root nodule formation but some hypotheses are
      emerging with regard to how the plant and microorganism manage to coexist. In
      particular, frankiae seem to present a nonpathogenic presence to the plant that
      may have the effect of minimizing some plant defense responses. Future studies
      using high-throughput approaches will likely clarify the range of bacterial
      responses to symbiosis that will need to be understood in light of the more
      rapidly advancing work on the plant host.

PMID- 21848399
TI  - Digital gene expression profiling of the Phytophthora sojae transcriptome.
AB  - The transcriptome of the oomycete plant pathogen Phytophthora sojae was profiled
      at ten different developmental and infection stages based on a 3'-tag digital
      gene-expression protocol. More than 90 million clean sequence tags were generated
      and compared with the P. sojae genome and its 19,027 predicted genes. A total of
      14,969 genes were detected, of which 10,044 were deemed reliable because they
      mapped to unambiguous tags. A comparison of the whole-library genes' expression
      patterns suggested four groups: i) mycelia and zoosporangia, ii) zoospores and
      cysts, iii) germinating cysts, and iv) five infection site libraries (IF1.5 to
      IF24h). The libraries from the different groups showed major transitional shifts
      in gene expression. From the ten libraries, 722 gene expression?pattern clusters
      were obtained and the top 16 clusters, containing more than half of the genes,
      comprised enriched genes with different functions including protein localization,
      triphosphate metabolism, signaling process, and noncoding RNA metabolism. An
      evaluation of the average expression level of 30 pathogenesis-related gene
      families revealed that most were infection induced but with diverse expression
      patterns and levels. A web-based server named the Phytophthora Transcriptional
      Database has been established.

PMID- 21848400
TI  - Exploring the function of alcohol dehydrogenases during the endophytic life of
      Azoarcus Sp. strain BH72.
AB  - The endophytic bacterium Azoarcus sp. strain BH72 is capable of colonizing the
      interior of rice roots, where it finds suitable physicochemical properties for
      multiplying and fixing nitrogen. Because these properties are poorly understood,
      a microtiter-plate-based screening of a transcriptional gfp (green fluorescent
      protein) fusion library of Azoarcus sp. grown under different conditions was
      performed. Monitoring of the GFP activity allowed the identification of a gene
      highly expressed in medium supplemented with ethanol. Sequence analysis revealed
      that this gene encodes a pyrrolo-quinoline quinone-dependent alcohol
      dehydrogenase (ADH). Inspection of the complete genome sequence of the Azoarcus
      sp. strain BH72 identified seven additional genes encoding putative ADH,
      indicating that BH72 is well equipped to survive in different environmental
      conditions offering various alcohols as carbon source. Analyses of these eight
      putative ADH showed that expression of three was induced by ethanol, of which two
      were also expressed inside rice roots. The fact that waterlogged plants such as
      rice accumulate ethanol suggests that ethanol occurs in sufficiently high
      concentration within the root to induce expression of bacterial ADH. Disruption
      of these two ADH evoked a reduced competitiveness to the wild type in colonizing
      rice roots internally. Thus, it is likely that ethanol is an important carbon
      source for the endophytic life of Azoarcus sp.

PMID- 21848401
TI  - Hepatoprotective role of vitamin B(12) and folic acid in arsenic intoxicated
      rats.
AB  - The present study elucidated the protective role of vitamin B(12) with folic acid
      against arsenic-induced hepatotoxicity in female rats. Ingestion of sodium
      arsenite- contaminated water [0.4 ppm/100 g body weight (b.w.)/day] in
      combination with vitamin B(12) plus folic acid (0.07 and 4.0 MUg,
      respectively/100 g b.w./day) for 24 days to Wistar rats offered a significant
      protection against alone arsenic-induced distorted liver function, damaged
      histoarchitecture, elevated oxidative stress, and DNA fragmentation of hepatic
      tissues. Arsenic only exposure decreased hepatic superoxide dismutase (SOD),
      catalase activities, and the level of nonprotein-soluble thiol (NPSH), with a
      concomitant increase in thiobarbituric acid reactive substances (TBARS) and
      conjugated dienes (CDs) in the liver. Vitamin supplementation restrained the
      increase of TBARS and CDs by restoring catalase, SOD, and NPSH levels. Restricted
      generation of free radicals may be correlated to the protection of DNA stability
      and hepatic morphology. This study explains the decisive role of vitamin B(12)
      with folic acid to ameliorate arsenic-mediated liver injuries.

PMID- 21848402
TI  - The effect of folic acid on ovine fetuses in utero during late gestation.
AB  - To investigate whether folic acid would have toxic effects on fetal cardiac,
      hepatic, and renal functions, this was the first in utero fetal study testing
      acute effects of folic acid at the last third of gestation. Folic acid (5 mg/day)
      or 0.9% saline as the control was intragastricly administrated into pregnant
      ewes. Both maternal and fetal blood were analyzed for pH, PO(2), PCO(2), SO(2)%,
      hemoglobin, hematocrit, glucose, lactic acid, osmolality, Na(+), and K(+)
      concentrations. Maternal and fetal cardiovascular functions were assessed by
      examining cardiac enzymes and cardiovascular responses in vivo. Fetal hepatic and
      renal functions were examined by analysis of biochemistry index and renal
      excretion. Folic acid did not alter the blood values in both ewes and fetuses.
      Cardiac enzyme activities remained unchanged, and no alteration in cardiovascular
      responses was observed. Folic acid did not affect fetal urine volume, urine
      electrolytes, and osmolality. Enzyme activities related to hepatic and renal
      functions were not changed. In addition, maternal application of folic acid had
      no effect on maternal and fetal lipid profile. The results showed that folic acid
      used (5 mg/day) during the last third of gestation did not cause biochemical
      changes related to cardiac, hepatic, and renal functions in both maternal and
      fetal sheep, providing new information for use of folic acid during late
      pregnancy.

PMID- 21848403
TI  - Diversity and evolution of the Hordeum murinum polyploid complex in Algeria.
AB  - Population diversity and evolutionary relationships in the Hordeum murinum L.
      polyploid complex were explored in contrasted bioclimatic conditions from
      Algeria. A multidisciplinary approach based on morphological, cytogenetic, and
      molecular data was conducted on a large population sampling. Distribution of
      diploids (subsp. glaucum) and tetraploids (subsp. leporinum) revealed a strong
      correlation with a North-South aridity gradient. Most cytotypes exhibit regular
      meiosis with variable irregularities in some tetraploid populations.
      Morphological analyses indicate no differentiation among taxa but high
      variability correlated with bioclimatic parameters. Two and three different
      nuclear sequences (gene coding for an unspliced genomic protein kinase domain)
      were isolated in tetraploid and hexaploid cytotypes, respectively, among which
      one was identical with that found in the diploid subsp. glaucum. The tetraploids
      (subsp. leporinum and subsp. murinum) do not exhibit additivity for 5S and 45S
      rDNA loci comparative with the number observed in the related diploid (subsp.
      glaucum). The subgenomes in the tetraploid taxa could not be differentiated using
      genomic in situ hybridization (GISH). Results support an allotetraploid origin
      for subsp. leporinum and subsp. murinum that derives from the diploid subsp.
      glaucum and another unidentified diploid parent. The hexaploid (subsp. leporinum)
      has an allohexaploid origin involving the two genomes present in the
      allotetraploids and another unidentified third diploid progenitor.

PMID- 21848404
TI  - Development of EST-SSR markers in castor bean (Ricinus communis L.) and their
      utilization for genetic purity testing of hybrids.
AB  - Expressed sequence tag (EST) databases offer opportunity for the rapid
      development of simple sequence repeat (SSR) markers in crops. Sequence assembly
      and clustering of 57 895 ESTs of castor bean resulted in the identification of 10
      960 unigenes (6459 singletons and 4501 contigs) having 7429 SSRs. On an average,
      the unigenes contained 1 SSR for every 1.23 kb of unigene sequence. The
      identified SSRs mostly consisted of dinucleotide (62.4%) and trinucleotide
      (33.5%) repeats. The AG class was the most common among the dinucleotide motifs
      (68.9%), whereas the AAG class (25.9%) was predominant among the trinucleotide
      motifs. A total of 611 primer pairs were designed for the SSRs, having repeat
      length more than or equal to 20 nucleotides, of which a set of 130 markers were
      tested and 92 of these yielding robust amplicons were analyzed for their utility
      in genetic purity assessment of castor bean hybrids. Nine markers were able to
      detect polymorphism between the parental lines of nine commercial castor bean
      hybrids (DCH-32, DCH-177, DCH-519, GCH-2, GCH-4, GCH-5, GCH-6, GCH-7, and RHC-1),
      and their utility in genetic purity testing was demonstrated. These novel EST-SSR
      markers would be a valuable addition to the growing molecular marker resources
      that could be used in genetic improvement programmes of castor bean.

PMID- 21848405
TI  - Origin of the H genome in StH-genomic Elymus species based on the single-copy
      nuclear gene DMC1.
AB  - Previous studies have suggested that the H haplome in Elymus could originate from
      different diploid Hordeum species, however, which diploid species best represent
      the parental species remains unanswered. The focus of this study seeks to
      pinpoint the origin of the H genome in Elymus. Allopolyploid Elymus species that
      contain the StH genome were analyzed together with diploid Hordeum species and a
      broad sample of diploid genera in the tribe Triticeae using DMC1 sequences. Both
      parsimony and maximum likelihood analyses well separated the American Hordeum
      species, except Hordeum brachyantherum subsp. californicum, from the H genome of
      polyploid Elymus species. The Elymus H-genomic sequences were formed into
      different groups. Our data suggested that the American Horedeum species, except
      H. brachyantherum subsp. californicum, are not the H-genomic donor to the Elymus
      species. Hordeum brevisubulatum subsp. violaceum was the progenitor species to
      Elymus virescens, Elymus confusus, Elymus lanceolatus, Elymus wawawaiensis, and
      Elymus caninus. Furthermore, North American H. brachyantherum subsp. californicum
      was a progenitor of the H genome to Elymus hystrix and Elymus cordilleranus. The
      H genomes in Elymus canadensis, Elymus sibiricus, and Elymus multisetus were
      highly differentiated from the H genome in Hordeum and other Elymus species. The
      H genome in both North American and Eurasian Elymus species was contributed by
      different Hordeum species.

PMID- 21848406
TI  - A finite element study on the effects of midsymphyseal distraction osteogenesis
      on the mandible and articular disc.
AB  - OBJECTIVE: To evaluate the biomechanical effect of midsymphyseal distraction
      osteogenesis with three types of distractors on the mandible and articular disc
      using a three-dimensional finite element model analysis. MATERIALS AND METHODS: A
      virtual model of the mandible was produced from computed tomography scan images
      of a healthy 27-year-old man. On the finite element model of the mandible,
      expansion of the bone-borne, tooth-borne, and hybrid type distractors were
      simulated with the jaw-closing muscles. The displacement and stress distribution
      of the mandible and articular disc were analyzed. RESULTS: With the bone-borne
      appliance the alveolar process area was displaced more than the basal bone area.
      The tooth-borne appliance displaced the mandibular body in a parallel manner and
      showed high level of the von Mises stress in the alveolar process and the ramal
      region as well as in the condylar neck area. The hybrid type showed medium amount
      of displacement and stress distribution compared with the bone-borne and tooth
      borne type. At the articular disc the compressive stress was concentrated in the
      anteromedial and posterolateral area, and it was highest in the tooth-borne
      distractor, followed by hybrid appliance and bone-borne appliance. CONCLUSIONS:
      The tooth-borne distractor produced more parallel bony widening in the
      midsymphyseal area and larger expansion in the molar region; however, it induced
      higher stress concentration on the articular disc than the hybrid appliance and
      bone-borne appliance. Whether any long-term side effects on the temporomandibular
      joint are anticipated, especially in tooth-borne distractor, remains to be
      investigated.

PMID- 21848407
TI  - Accuracy of orthodontic miniscrew implantation guided by stereolithographic
      surgical stent based on cone-beam CT-derived 3D images.
AB  - OBJECTIVE: To develop surgical stents for cone-beam computed tomography (CBCT) 3
      dimensional (3D) image-based stent-guided orthodontic miniscrew implantation and
      to evaluate its accuracy. MATERIALS AND METHODS: Ten surgical stents were
      fabricated with stereolithographic appliances (SLAs) according to 3D CBCT image
      based virtual implantation plans. Thirty self-drilling miniscrews were implanted
      at two to three positions on each side of the maxillary or mandibular posterior
      arches in three phantoms: 20 guided by 10 surgical stents in two phantoms (stent
      group) and 10 guided freehand in one phantom (freehand group). Six parameters
      (mesiodistal and vertical deviations at the corona and apex and mesiodistal and
      vertical angular deviations) were measured to compare variations between the
      groups. RESULTS: No root damage was found in the stent group, whereas four of 10
      miniscrews contacted with roots in the freehand group. In the stent group,
      deviations in the mesiodistal and vertical directions were 0.15 +/- 0.09 and 0.19
      +/- 0.19 mm at the corona, respectively, and 0.28 +/- 0.23 and 0.33 +/- 0.25 mm
      at the apex, respectively; angular deviations in the mesiodistal and vertical
      directions were 1.47 degrees  +/- 0.92 degrees  and 2.13 degrees  +/- 1.48
      degrees , respectively. In the freehand group, the corresponding results were
      0.48 +/- 0.46 mm and 0.94 +/- 0.87 mm (corona), 0.81 +/- 0.61 mm and 0.78 +/-
      0.49 mm (apex), and 7.49 degrees  +/- 6.09 degrees  and 6.31 degrees  +/- 3.82
      degrees . Significant differences were found in all six parameters between the
      two groups (Student's t-test, P < .05). CONCLUSIONS: 3D CBCT image-based SLA
      fabricated surgical stents can provide a safe and accurate method for miniscrew
      implantation.

PMID- 21848408
TI  - Effectiveness of an indirect bonding technique in reducing plaque accumulation
      around braces.
AB  - OBJECTIVE: To evaluate if the use of an indirect braces bonding protocol for
      localized enamel etching and adhesive application could help reduce plaque
      accumulation and demineralization around the brackets compared with a
      conventional direct-bonding technique. MATERIALS AND METHODS: Thirty patients
      were bonded with a split-mouth approach: two randomly selected opposite quadrants
      were used as the test sides and the other two as control sides. During the first
      6 months, the plaque presence around the braces was recorded monthly according to
      a plaque accumulation index (PAI), as was the presence of demineralization. PAI
      values were measured at each of the four bracket sides for every bonded tooth.
      Analysis of variance was used to identify significant differences between
      different bracket margins and between test and control sides. RESULTS: Test and
      control sides differed significantly for PAI measurements from t(1) (1 month
      after bonding) to t(4) (4 months after bonding), with the highest value of
      significance (P < .001) at t(1) but with no significant differences from t(5) to
      t(7) (treatment end). Considering whole-mouth results, different bracket margin
      PAI scores did not differ significantly. PAI scores were higher at t(1) and
      progressively decreased during the treatment. At debonding, the onset of 21 new
      white spots was recorded overall for the control sides and eight new white spots
      for the test sides. CONCLUSION: Especially during the first 4 months after
      brackets placement, this indirect bonding protocol allowed for significant
      reduction in plaque accumulation around the braces and reduced onset of white
      spots during the orthodontic treatment.

PMID- 21848409
TI  - Diesel exhaust inhalation induces heat shock protein 70 expression in vivo.
AB  - Exposure to urban air pollution is an independent risk factor for increased
      cardiovascular diseases. Heat shock protein 70 (HSP70) has been implicated in the
      pathogenesis of vascular dysfunction and cardiovascular diseases. This study has
      been designed to determine whether inhalation of urban air induces HSP70
      expression in the lung and blood as well as the association of HSP70 and air
      pollution-induced vascular dysfunction. Apolipoprotein E (Apo-E) deficient mice
      were exposed to diesel exhaust (DE) either acutely (3 days, 200 or 400 ug/m(3)
      for 6 h/day) or chronically (7 weeks, 200 or 400 ug/m(3) for 6 h/day). HSP70 was
      measured in the lung using immunohistochemistry, and in the plasma by ELISA.
      Abdominal aorta rings were used to determine vascular functional responses.
      Chronic DE-exposure increased the fraction of HSP70 positive alveolar macrophages
      (AM) that was related to the fraction of particle-laden AM in the lung (r(2) = 
      0.48, p <0.01). Chronic DE-exposure increased plasma HSP70 levels and reduced
      blood vessel responses to phenylephrine (PE). The fraction of particle-laden
      HSP70 positive AM was associated with abnormal vasoconstriction responses to PE
      induced by DE-exposure (r(2) = 0.12, p = 0.02). Our results show that chronic
      inhalation of DE increases HSP70 expression in the lung and systemic circulation,
      and we postulate that HSP70 possibly contributes to air pollution induced
      vascular dysfunction and cardiovascular diseases.

PMID- 21848410
TI  - Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and
      presentation of endometriosis.
AB  - Pelvic endometriosis is a chronic inflammatory disease with an immunological
      background. Yet there is paucity of contemporary research exploring both the
      angiogenic cytokines, leptin and IL-8 for a possible role in its pathophysiology.
      OBJECTIVE: To compare levels of both leptin and IL-8 in peritoneal fluid (PF) in
      women with endometriosis vs. fertile controls and correlate with disease stage,
      type and symptoms. MATERIALS AND METHODS: PF from 58 women with endometriosis and
      28 women undergoing tubal ligation was collected at laparoscopy and leptin and IL
      8 levels were measured using ELISA. Results showed significantly higher levels of
      both cytokines in women with endometriosis. Significantly higher leptin and IL-8
      levels were demonstrated in patients with early peritoneal (ASRM stage I and II)
      and advancing disease (ASRM stage III and IV), respectively. Levels of leptin/IL
      8 were significantly lower in patients with endometrioma (4.8 ng/mL/32 pg/mL) vs.
      implants (13.0 ng/mL/68 pg/mL). There was no correlation of infertility or
      chronic pelvic pain with these levels. CONCLUSION: Both leptin and IL-8 levels
      are raised in PF of women with endometriosis reflecting inflammation and
      dysregulated immunomodulation. Higher levels of leptin were seen in early stages;
      IL-8 seems to stimulate the disease in a dose-dependent manner.

PMID- 21848411
TI  - The effect of resveratrol on blood pressure in a rat model of preeclampsia.
AB  - OBJECTIVE: To examine the hypothesis that resveratrol administration could result
      in blood pressure and blood flow decrease in a rat preeclampsia model. MATERIALS
      AND METHODS: Desoxycorticosterone acetate (DOCA) was used to produce
      hypertension. The Wistar albino rats were divided randomly into three groups:
      control (n = 12), DOCA injected (n = 11), and DOCA injected and resveratrol
      treated (n = 13). Rats were sacrificed on gestational day 16-20. The systolic
      blood pressure was measured by the tail-cuff method. Urine protein was expressed
      as protein/creatinine. Laser Doppler measurements of the blood flow were made in
      one placenta, the left kidney and both parietal lobes of brain. Placentas were
      examined by light microscopy. RESULTS: DOCA injected group exhibited significant
      differences in blood pressure and protein/creatinine. Mean blood pressure in DOCA
      treated rats was 130.1 +/- 12.9 mmHg at baseline and 148.4 +/- 20.1 mmHg at the
      time of euthanization (p = 0.044). Resveratrol did not significantly affect blood
      pressure, placental and renal blood flows. There were also no significant
      differences in placental pathology parameters among the three groups. CONCLUSION:
      The present study demonstrated that resveratrol did not decrease blood pressure,
      and did not result in a significant response in blood flows and placental
      pathology parameters.

PMID- 21848412
TI  - Neoskin development in the fetus with the use of a three-layer graft: an animal
      model for in utero closure of large skin defects.
AB  - OBJECTIVE: To assess the ability of a three-layer graft in the closuse of large
      fetal skin defects. METHODS: Ovine fetuses underwent a large (4 * 3 cm) full
      thickness skin defect over the lumbar region at 105 days' gestation (term = 140
      days). A bilaminar artificial skin was placed over a cellulose interface to cover
      the defect (3-layer graft). The skin was partially reapproximated with a
      continuous nylon suture. Pregnancy was allowed to continue and the surgical site
      was submitted to histopathological analysis at different post-operative
      intervals. RESULTS: Seven fetuses underwent surgery. One maternal/fetal death
      occurred, and the remaining 6 fetuses were analyzed. Artificial skin adherence to
      the wound edges was observed in cases that remained in utero for at least 15
      days. Neoskin was present beneath the silicone layer of the bilaminar artificial
      skin. CONCLUSIONS: Our study shows that neoskin can develop in the fetus using a
      3-layer graft, including epidermal growth beneath the silicone layer of the
      bilaminar skin graft. These findings suggest that the fetus is able to
      reepithelialise even large skin defects. Further experience is necessary to
      assess the quality of this repair.

PMID- 21848413
TI  - Amenorrhea and BMI as independent determinants of patient satisfaction in LNG-IUD
      users: cross-sectional study in a Central European district.
AB  - OBJECTIVE: This study investigated the satisfaction of women carrying the LNG-IUD
      and determined influencing factors, especially considering bleeding patterns and
      body mass index (BMI). DESIGN: Cross sectional study. SETTING: Gynecological
      offices in a Central European district. PARTICIPANTS: 1825 women aged between 18
      and 60 years. MEASUREMENT: While sitting in the waiting room, voluntary patients
      had to answer a questionnaire about their experiences with the levonorgestrel
      intrauterine device. One question was used to determine whether the women were
      current, former or not users of the intrauterine coil. RESULTS: 415 women who had
      some experiences with Mirena were found. Overall, 266 (65.7%) were "very
      satisfied," 83 (20.5%) "quite satisfied," 18 (4.4%) "moderate satisfied," 19
      (4.7%) "less satisfied," and the same amount "really not satisfied" with the
      hormonal coil. Women with amenorrhea were more often "very satisfied" in general,
      than women with hypermenorrhea (178 (67.9%) vs. 3 (1.1%) p < 0.001). Concerning
      bleeding patterns, 295 (74.1%) were "very satisfied" and 23 (5.8%) "really not
      satisfied". 203 (91.0%) of all amenorrhoeic women were "very satisfied" with
      their bleeding patterns, but only 2 (9.5%) of all women with hypermenorrhea (p <
      0.001 for alpha = 0.05). Amenorrhea particularly occurred in women who had a
      significantly lower body mass index (24.4 +/- 4.4 kg/m(2) vs. 27.6 +/- 6.5
      kg/m(2) in women with hypermenorrhea, p = 0.018 for alpha = 0.05). After
      allocating women to the widely used BMI-categories (underweight, normal weight,
      overweight, obese class I and II) it was evident, that normally weighted women
      tend toward amenorrhea as well at the beginning of LNG-IUD use as well after 4-5
      years of use. In contrast to this, overweighed and obese women tend more often to
      amenorrhea at the end of use, but not at the beginning (72.7% and 55.6% vs. 25.0%
      and 0%). Women with a lower BMI were more often "very satisfied" concerning
      bleeding patterns, but not concerning the general satisfaction. CONCLUSION: Our
      study showed much evidence, that amenorrhea occurs more often in women with lower
      BMI contrary to women with a higher one-especially at the beginning of LNG- IUD
      use. Furthermore amenorrhea was mostly considered to be a positive menstrual
      change.

PMID- 21848414
TI  - An analysis of selection on candidate genes for regulation, mobilization, uptake,
      and transport of iron in maize.
AB  - Insufficient iron (Fe) availability, which frequently occurs in soils with high
      pH levels, can lead to leaf chlorosis, a reduced Fe content in harvest products,
      and yield reduction in maize. The objectives of this study were (i) to describe
      patterns of sequence variation of 14 candidate genes for mobilization, uptake,
      and transport of Fe in maize, as well as regulatory function on these processes;
      (ii) to examine whether Fe-efficiency is an adaptive trait by determining if
      these genes were targets of selection during domestication; and (iii) to test if
      the allele distribution at these candidate genes is different for the different
      subpopulations of maize. The nucleotide diversity of Mtk was reduced by 78% in
      maize compared with teosinte. The results of our study revealed for the genes
      Naat1, Nas1, Nramp3, Mtk, and Ys1 a selective sweep, which suggests that these
      genes might be important for the fast adaptation of maize to new environments
      with different Fe availabilities.

PMID- 21848417
TI  - Response to "The statistics of skin impedance".

PMID- 21848415
TI  - The quantification of placebo effects within a general model of health care
      outcomes.
AB  - OBJECTIVES: The objective of this study was to test a model of placebo effects in
      the context of a general model of health care outcomes. DESIGN: The design of
      this study was a multisite, double-blind, placebo-controlled crossover trial.
      SETTINGS: The study was conducted at The University of Washington Hospital,
      Seattle, Washington, Cooper Hospital/University Medical Center, Camden, New
      Jersey, and at the Neurology Center of Fairfax, Fairfax, Virginia. SUBJECTS: One
      hundred and seventeen (117) patients diagnosed with Multiple Sclerosis were
      enrolled in the study. INTERVENTION: Subjects had daily exposure to a pulsing
      electromagnetic generator. OUTCOME MEASURES: The outcome measures were the
      average score of three quality-of-life indices: the Modified Fatigue Impact
      Scale, the Medical Outcomes Study Pain Effects Scale, and the Spasticity Effects
      Scale. RESULTS: Placebo responders scored higher in the personality trait of
      Absorption compared with nonresponders (p<0.01). Placebo responders were more
      confident that the sham device was active compared to placebo nonresponders
      (p<0.009). The two factors of confidence in the treatment and Absorption
      accurately identified 80% of placebo responders in a discriminant analysis
      (p<0.0004). CONCLUSIONS: Placebo effects are best understood when integrated in a
      general model of health care outcomes.

PMID- 21848418
TI  - Vaccines of the 21st century and vaccinomics: data-enabled science meets global
      health to spark collective action for vaccine innovation.

PMID- 21848419
TI  - Steering vaccinomics innovations with anticipatory governance and participatory
      foresight.
AB  - Vaccinomics is the convergence of vaccinology and population-based omics
      sciences. The success of knowledge-based innovations such as vaccinomics is not
      only contingent on access to new biotechnologies. It also requires new ways of
      governance of science, knowledge production, and management. This article
      presents a conceptual analysis of the anticipatory and adaptive approaches that
      are crucial for the responsible design and sustainable transition of vaccinomics
      to public health practice. Anticipatory governance is a new approach to manage
      the uncertainties embedded on an innovation trajectory with participatory
      foresight, in order to devise governance instruments for collective "steering" of
      science and technology. As a contrast to hitherto narrowly framed "downstream
      impact assessments" for emerging technologies, anticipatory governance adopts a
      broader and interventionist approach that recognizes the social construction of
      technology design and innovation. It includes in its process explicit mechanisms
      to understand the factors upstream to the innovation trajectory such as
      deliberation and cocultivation of the aims, motives, funding, design, and
      direction of science and technology, both by experts and publics. This upstream
      shift from a consumer "product uptake" focus to "participatory technology design"
      on the innovation trajectory is an appropriately radical and necessary departure
      in the field of technology assessment, especially given that considerable public
      funds are dedicated to innovations. Recent examples of demands by research
      funding agencies to anticipate the broad impacts of proposed research--at a very
      upstream stage at the time of research funding application--suggest that
      anticipatory governance with foresight may be one way how postgenomics scientific
      practice might transform in the future toward responsible innovation. Moreover,
      the present context of knowledge production in vaccinomics is such that policy
      making for vaccines of the 21st century is occurring in the face of uncertainties
      where the "facts are uncertain, values in dispute, stakes high and decisions
      urgent and where no single one of these dimensions can be managed in isolation
      from the rest." This article concludes, however, that uncertainty is not an
      accident of the scientific method, but its very substance. Anticipatory
      governance with participatory foresight offers a mechanism to respond to such
      inherent sociotechnical uncertainties in the emerging field of vaccinomics by
      making the coproduction of scientific knowledge by technology and the social
      systems explicit. Ultimately, this serves to integrate scientific and social
      knowledge thereby steering innovations to coproduce results and outputs that are
      socially robust and context sensitive.

PMID- 21848420
TI  - Benefits of adding lidocaine to a hyaluronic gel - Stylage(r) M.
AB  - Although the benefits of adding lidocaine are recognized in terms of relieving
      the pain experienced upon injection, it would appear beneficial to establish the
      impact of lidocaine within the Stylage(r) range, the only one to incorporate both
      an anaesthetic (lidocaine) and an antioxidant in the form of mannitol in its
      crosslinked gel of HA. A clinical follow-up was carried out at 11 centres over a
      period of 6-8 months, depending on the practitioner, and involved 84 patients.
      The aim of this study was to determine fact from fiction with regards to the
      benefits of adding local anaesthetic to a filler : 1.Does this addition offer a
      real benefit in relation to the basic gel? 2)Could it be the cause of other
      incidents directly linked to lidocaine? 3. Could it have an impact on the
      durability of the result?

PMID- 21848421
TI  - Intense pulsed light for the treatment of rosacea and telangiectasias.
AB  - Abstract Background: Rosacea is a chronic disease that affects the aesthetic
      appearance of skin. The use of intense pulsed light (IPL) has shown significant
      clearing in erythema, telangiectasia, and papules in rosacea. We seek parameters
      for IPL that will achieve optimal reduction in the appearance of rosacea with
      minimal adverse effects. OBJECTIVE: To investigate the use of IPL on 102 patients
      at various parameters (fluence and pulse duration) in the treatment of rosacea.
      METHODS: 102 patients with mild to severe rosacea were treated with IPL treatment
      using the NaturaLight IPL system (Focus Medical, Bethel, CT). Patients received
      treatments at 1-3 week intervals, with an average of 7.2 treatments. The Reveal
      Imager (Canfield Scientific, Fairfield, NJ) was used for photodocumentation and
      analyses. RESULTS: Treatments were given at 2.5/5 ms double, triple, or quadruple
      pulsed with 20-30 ms delay time. A 530 nm filter was used with fluences varying
      from 10-30 J/cm(2), or 10-20 J/cm(2) with a 420 nm filter for those patients with
      acneiform breakouts in addition to telangiectasias. 80% of patients had reduction
      in redness, 78% of patients reported reduced flushing and improved skin texture,
      and 72% noted fewer acneiform breakouts. There were no complications or adverse
      effects. CONCLUSION: The use of IPL at specified parameters provides optimal
      therapy for the treatment of rosacea.

PMID- 21848422
TI  - Infrared spectroscopic characterization of organic matter associated with
      microbial bioalteration textures in basaltic glass.
AB  - Microorganisms have been found to etch volcanic glass within volcaniclastic
      deposits from the Ontong Java Plateau, creating micron-sized tunnels and pits.
      The fossil record of such bioalteration textures is interpreted to extend back
      ~3.5 billion years to include meta-volcanic glass from ophiolites and Precambrian
      greenstone belts. Bioalteration features within glass clasts from Leg 192 of the
      Ocean Drilling Program were investigated through optical microscopy and Fourier
      transform infrared (FTIR) spectroscopy of petrographic thin sections. Extended
      depth of focus optical microscopic imaging was used to identify bioalteration
      tubules within the samples and later combined with FTIR spectroscopy to study the
      organic molecules present within tubule clusters. The tubule-rich areas are
      characterized by absorption bands indicative of aliphatic hydrocarbons, amides,
      esters, and carboxylic groups. FTIR analysis of the tubule-free areas in the
      cores of glass clasts indicated that they were free of organics. This study
      further constrains the nature of the carbon compounds preserved within the
      tubules and supports previous studies that suggest the tubules formed through
      microbial activity.

PMID- 21848423
TI  - Barriers to prevention of HIV type 1 mother-to-child-transmission in Bahia,
      Brazil.

PMID- 21848425
TI  - A cannabinoid ligand, anandamide, exacerbates endotoxin-induced uveitis in
      rabbits.
AB  - PURPOSE: This study aimed to investigate the effects of anandamide or
      arachidonylethanolamide (AEA), an endogenous cannabinoid receptor agonist, on
      intraocular inflammation in an endotoxin-induced uveitis (EIU) model in rabbits.
      METHODS: Forty New Zealand albino male rabbits were used (5 groups, 8 animals in
      each). After establishment of sufficient anesthesia, animals were taken under
      surgery for intravitreal injections. A maximum amount of 50 MUL of solution was
      injected into the central vitreous with a 30-gauge needle. In the control group,
      sterile saline was injected into the right eyes of the animals. Likewise, AEA
      (10(-5) M) in the second group, lipopolysaccharide (LPS; 100 ng) in the third
      group, and AEA (10(-5) M) and LPS (100 ng) in the fourth group were administered.
      Fifth group received 0.1 mL subtenon injection of AM251 (10(-5) M), a CB(1)
      receptor antagonist, 30 min prior to intravitreal LPS (100 ng) and AEA (10(-5) M)
      injection. At 24 h after the surgical intervention, clinical evaluation was
      performed and animals were then euthanized with 100 mg/kg intravenous
      pentobarbital injections. Immediately after the induction of pentobarbital
      anesthesia, the anterior chamber of the eyes was quickly punctured using a 30
      gauge needle to drain aqueous humor (AH) and obtained specimens were used for
      cell count, protein measurement, and microbiological contamination tests. After
      AH collection, enucleation was performed and enucleated material was kept for the
      pathological evaluation. RESULTS: AEA caused an overall worsening of EIU in
      studied eyes. It significantly increased the detrimental effects of endotoxin, as
      assessed by clinical investigation of ocular inflammation, AH leukocyte content,
      and AH protein concentrations. CB(1)-receptor antagonist AM251 administration
      reversed some components of this AEA-induced exacerbation to significant extents.
      CONCLUSION: AEA exacerbated EIU in rabbit eyes. AM251 has been found beneficial
      to prevent AEA's aggravating impact on EIU. As AEA is a treatment choice for
      lowering intraocular pressure in ophthalmology practice, concurrent use of CB(1)
      receptor antagonists may be a questionable strategy in cases of secondary
      glaucoma, to avoid aggravation of the present inflammation.

PMID- 21848424
TI  - Genetic associations with metabolic syndrome and its quantitative traits by
      race/ethnicity in the United States.
AB  - BACKGROUND: Elevated insulin resistance (IR), triglycerides (TG), body mass index
      (BMI), and waist circumference (WC) are features of the metabolic syndrome.
      Although several single-nucleotide polymorphisms (SNPs) associated with these
      traits have been reported, no study has reported their risk allele frequencies
      and effect sizes among the major U.S. race/ethnic groups in a nationally
      representative sample. METHODS: We compared the risk allele frequencies of eight
      SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non
      Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of
      the National Health and Nutrition Examination Study III (NHANES III). In
      regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested
      whether the SNP effect sizes on these traits varied by race/ethnicity. RESULTS:
      Risk allele frequencies varied by race/ethnicity for all eight loci (P<0.0001).
      The directionality of effects of the variants on IR, TG, WC, and BMI was
      generally consistent with previous observations and did not differ by
      race/ethnicity (P>0.001), although our study had low power for this test. No SNP
      predicted metabolic syndrome in any of the three groups (P>0.05). CONCLUSIONS:
      The significance of racial/ethnic differences in risk allele frequencies merits
      consideration if genetic discoveries are to have clinical and public health
      applicability.

PMID- 21848426
TI  - Polymorphisms of folate pathway enzymes (methylenetetrahydrofolate reductase and
      thymidylate synthase) and their relationship with thymidylate synthase expression
      in human astrocytic tumors.
AB  - Two important polymorphisms of folate cycle enzymes, methylenetetrahydrofolate
      reductase (MTHFR) C677T and thymidylate synthase (TS) enhancer region (TSER) 28
      bp tandem repeat, are related to risk of various types of cancer, including brain
      tumors, although there are few studies on this subject. A case-control study of
      these two polymorphisms in astrocytomas of different grades was carried out using
      polymerase chain reaction-restriction fragment length polymorphism, also
      determining the immunohistochemical expression of TS. The MTHFR 677 TT genotype
      was less associated with astrocytic tumors (odds ratio [OR]=0.00; p=0.0238), but
      the TSER polymorphism did not show any significant association. Combined genotype
      TT-double repeats/triple repeats (2R/3R) had a protective effect against
      astrocytomas (OR=0.00; p=0.0388). Expression of TS protein was observed in the
      majority of cases, with grade IV tumors being the exception. Moreover, the median
      H-score for the pilocytic astrocytomas was significantly higher when compared
      with that for diffuse tumors. There was an inverse correlation between the 2R/2R
      genotype and the highest TS-expressing tumors, and 3R/3R was relatively more
      frequent among the tumors grouped in the third and fourth quartiles. Our results
      provide support for the role of MTHFR and TS polymorphism in gliomagenesis,
      possibly because of the alteration of DNA methylation and repair status.
      Moreover, high levels of TS expression were detected in these tumors.

PMID- 21848427
TI  - Intercalation and induction of strand breaks by adriamycin and daunomycin: a
      study with human genomic DNA.
AB  - The anticancer drugs Adriamycin (ADR) and Daunomycin (DNM) of the anthracycline
      family are effective in treating a variety of cancers. Although their
      interactions with other cellular targets may play a role in the selective
      cytotoxicity of these drugs, it is generally believed that intercalation with DNA
      is essential for their activity. However, a relationship has not yet been
      established between intercalation and cellular processes leading to cytotoxicity.
      The present study was designed to investigate the relationship, if any, between
      intercalation and DNA strand breaks. ADR and DNM were observed to be strong
      intercalators of human genomic DNA by absorption and fluorimetric methods that
      were further substantiated by rise in thermal melting temperature. DNM is the
      better intercalator of the two, which is also evident from circular dichroic
      spectral changes. DNA strand breaks, considered to be an index of genotoxicity,
      was assayed by single cell gel electrophoresis (SCGE; comet assay). ADR and DNM
      induced equivalent genotoxicity in normal human lymphocytes at a clinically used
      dose, which was observed to be independent of intercalation efficiency though
      positively correlated to yield of reactive oxygen species.

PMID- 21848428
TI  - Impact of genetic variations of the CYP1A1, GSTT1, and GSTM1 genes on the risk of
      coronary artery disease.
AB  - Carcinogenic and toxic molecules produce DNA adducts that contribute to the
      development of atherosclerosis. Genetic polymorphisms of xenobiotic-detoxified
      enzymes, which control the level of DNA adducts, may affect both enzymatic
      activity and individual susceptibility to coronary artery disease (CAD). In this
      study we investigated the effects of genetic polymorphisms of the CYP1A1*2C,
      GSTT1, and GSTM1 enzymes on CAD risk in a Turkish population. Genotypes were
      determined for 132 CAD patients and 151 healthy controls by the polymerase chain
      reaction/restriction fragment length polymorphism method. There were no
      significant differences between patients and controls in terms of CYP1A1, GSTT1,
      and GSTM1 genotypes. Analysis of the possible interactions between the genotypes,
      after adjustment for the risk factors, demonstrated that individuals carrying
      CYP1A1 variant GSTT1 null genotypes had an 8.907-fold increased CAD risk compared
      to their wild status (p<0.05). We suggest that genetic polymorphisms of
      xenobiotic-metabolizing enzymes could play an important role in CAD. Therefore,
      CYP1A1 and GSTM1 polymorphisms should be considered as important parameters for
      the prediction of CAD.

PMID- 21848429
TI  - Mitochondria DNA polymorphisms are associated with susceptibility to
      endometriosis.
AB  - Because energy production involves oxidative phosphorylation, mitochondria are
      major sources of reactive oxygen species in the cell. Recent findings indicate
      that mitochondrial DNA (mtDNA) variants may play a role in the etiology of
      certain autoimmune and chronic inflammatory diseases. The aim of this study was
      to investigate the possible association between mtDNA polymorphisms and
      susceptibility to endometriosis. This study included 198 patients with
      histologically confirmed endometriosis and 167 patients without endometriosis as
      controls. Common variants of mtDNA at nt10398 (A/G transition), nt13708 (G/A
      transition), and nt16189 (T/C transition) were detected using polymerase chain
      reaction. An association study was performed with a chi-square test and logistic
      regression analysis. The prevalence of the mtDNA nt16189 variant was higher in
      patients with endometriosis (46.0%, 91 of 198) than in controls (34.7%, 58 of
      167) (p=0.030) with odds ratio (OR) of 1.98 (95% confidence interval [CI]: 1.04
      3.78). A combination of the 10398 and 16189 variants was also associated with
      increased risk for endometriosis (OR=1.90, 95% CI: 1.13-3.18, p=0.015). These
      associations remained significant even after adjusting for age and body mass
      index. Our data strongly suggest that the mtDNA 16189 variants and the
      combination of mtDNA 16189 and 10398 variants increase susceptibility to
      endometriosis.

PMID- 21848430
TI  - Differing effects of azithromycin and doxycycline on cytokines in cells from
      Chlamydia trachomatis-infected women.
AB  - Chlamydial infection of the lower genital tract usually spreads to the upper
      genital tract and is then responsible for more serious consequences, such as
      infertility, ectopic pregnancy, pelvic pain, and pelvic inflammatory disease.
      Genital infection with Chlamydia trachomatis and the resulting cytokine response
      largely determines the outcome of infection and disease. To date, studies showing
      comparative effects of azithromycin and doxycycline treatment for C. trachomatis
      infection in women with reproductive sequelae like infertility and their effect
      on immune molecules like cytokines are lacking. Hence, our objective was to study
      the effect of azithromycin and doxycycline in vitro on cytokines in cells from C.
      trachomatis-positive fertile and infertile women as well as their efficacy in C.
      trachomatis infection. Fertile and infertile women with primary and recurrent C.
      trachomatis infection attending the gynecology outpatient department of
      Safdarjung Hospital, New Delhi, India, were enrolled. Enzyme-linked immunosorbent
      assay and real-time reverse transcription-polymerase chain reaction was performed
      for evaluating cytokines in cells stimulated with chlamydial elementary bodies
      (EBs) in the presence and absence of antibiotics (azithromycin and doxycycline).
      C. trachomatis-infected women were also followed up to assess the efficacy of
      azithromycin and doxycycline. We observed inhibition of cytokines (interleukin
      [IL]-1beta (beta), IL-6, IL-8, IL-10, and tumor necrosis factor-alpha) in the
      presence of azithromycin in EB-stimulated cells from both fertile and infertile
      women with primary and recurrent C. trachomatis infection. However, in presence
      of doxycycline, inhibition of cytokines (IL-1beta and IL-6) was only observed in
      stimulated cells from fertile women with primary C. trachomatis infection. The
      clinical efficacy of azithromycin was also better than doxycycline in recurrent
      C. trachomatis infection in women with complications such as infertility.
      Overall, this study suggests that azithromycin treatment with broader
      immunomodulatory effects may be preferable to doxycycline for the treatment of
      recurrent C. trachomatis infection associated with infertility.

PMID- 21848431
TI  - Parameters of care for craniosynostosis.
AB  - BACKGROUND: A multidisciplinary meeting was held from March 4 to 6, 2010, in
      Atlanta, Georgia, entitled "Craniosynostosis: Developing Parameters for
      Diagnosis, Treatment, and Management." The goal of this meeting was to create
      parameters of care for individuals with craniosynostosis. METHODS: Fifty-two
      conference attendees represented a broad range of expertise, including
      anesthesiology, craniofacial surgery, dentistry, genetics, hand surgery,
      neurosurgery, nursing, ophthalmology, oral and maxillofacial surgery,
      orthodontics, otolaryngology, pediatrics, psychology, public health, radiology,
      and speech-language pathology. These attendees also represented 16 professional
      societies and peer-reviewed journals. The current state of knowledge related to
      each discipline was reviewed. Based on areas of expertise, four breakout groups
      were created to reach a consensus and draft specialty-specific parameters of care
      based on the literature or, in the absence of literature, broad clinical
      experience. In an iterative manner, the specialty-specific draft recommendations
      were presented to all conference attendees. Participants discussed the
      recommendations in multidisciplinary groups to facilitate exchange and consensus
      across disciplines. After the conference, a pediatric intensivist and social
      worker reviewed the recommendations. RESULTS: Consensus was reached among the 52
      conference attendees and two post hoc reviewers. Longitudinal parameters of care
      were developed for the diagnosis, treatment, and management of craniosynostosis
      in each of the 18 specialty areas of care from prenatal evaluation to adulthood.
      CONCLUSIONS: To our knowledge, this is the first multidisciplinary effort to
      develop parameters of care for craniosynostosis. These parameters were designed
      to help facilitate the development of educational programs for the patient,
      families, and health-care professionals; stimulate the creation of a national
      database and registry to promote research, especially in the area of outcome
      studies; improve credentialing of interdisciplinary craniofacial clinical teams;
      and improve the availability of health insurance coverage for all individuals
      with craniosynostosis.

PMID- 21848432
TI  - A national study of out-of-pocket expenditures for mammography screening.
AB  - OBJECTIVES: To identify variations in screening mammography expenditures,
      primarily out-of-pocket and total expenditures, of women 40-64 years of age in
      the United States and factors associated with variations. METHODS: Retrospective
      analysis of data collected from the 2007 and 2008 Medical Expenditure Panel
      Survey (MEPS). The sample included 2020 women 40-64 years of age who received one
      mammogram in 2007 or 2008. Ordinary least squares regression was used to describe
      relationships among out-of-pocket mammography expenditures, total mammography
      expenditures, and out-of-pocket mammography expenditures as a percentage of total
      mammography expenditures and such independent variables as insurance status and
      type, income, region of the United States, and type of facility where a mammogram
      was received. RESULTS: The average out-of-pocket expenditure for a mammogram in
      2007 or 2008 was $33, representing 14.1% of the total mammogram expenditure
      ($266). After controlling for demographic and health factors, women who were
      uninsured, were from the Midwest, and had a mammogram at an office-based facility
      had greater out-of-pocket mammography expenditures. Women who were uninsured,
      lived in the South, and received their mammogram at an office-based facility had
      out-of-pocket mammography expenditures that represented a greater proportion of
      the total mammography expenditures. CONCLUSIONS: Large variations in out-of
      pocket expenditures were observed among women with and without insurance and
      between insurance types, geographic regions of the United States, and types of
      facilities where mammograms were received. A higher financial burden of
      mammography screening among some subgroups of women may act as a barrier to
      future mammography screening.

PMID- 21848433
TI  - Composite reviews from the 2010 Neurobiology of Stress Workshop.

PMID- 21848434
TI  - Chronic stress, metabolism, and metabolic syndrome.
AB  - The prevalence of obesity has rapidly escalated and now represents a major public
      health concern. Although genetic associations with obesity and related metabolic
      disorders such as diabetes and cardiovascular disease have been identified,
      together they account for a small proportion of the incidence of disease.
      Environmental influences such as chronic stress, behavioral and metabolic
      disturbances, dietary deficiency, and infection have now emerged as contributors
      to the development of metabolic disease. Although epidemiological data suggest
      strong associations between chronic stress exposure and metabolic disease, the
      etiological mechanisms responsible remain unclear. Mechanistic studies of the
      influence of chronic social stress are now being conducted in both rodent and
      nonhuman primate models, and phenotypic results are consistent with those in
      humans. The advantage of these models is that potential neural mechanisms may be
      examined and interventions to treat or prevent disease may be developed and
      tested. Further, circadian disruption and metabolic conditions such as diabetes
      mellitus could increase susceptibility to other stressors or serve as a stressor
      itself. Here, we review data from leading investigators discussing the
      interrelationship between chronic stress and development of metabolic disorders.

PMID- 21848435
TI  - Effects of stress across the lifespan.
AB  - Stress is a known precipitant for metabolic and neurological diseases, with
      sensitive periods identified across the developmental continuum from conception
      to old age. However, the effects of stress may vary depending on the point or
      points along the developmental trajectory when adversity strikes. Past research
      has emphasized the consequences of stress on fully developed physiological
      systems in the brain and periphery, but more recent studies have explored the
      impact of stress on systems at different stages of maturation, with differential
      effects being revealed. This review provides an overview of the diverse effects
      of stress at critical developmental stages and the potential outcomes that may be
      associated with experiencing environmental adversity during ontogeny.

PMID- 21848437
TI  - The penultimate issue of the year.

PMID- 21848439
TI  - Retrospective study of deep surgical site infections following spinal surgery and
      the effectiveness of continuous irrigation.
AB  - Surgical site infection (SSI) is an unfortunate and unpreventable complication of
      any surgical intervention including spinal surgery. Early deep SSI (EDSSI) after
      instrumented spinal fusion are particularly difficult to manage due to the
      implanted, and possibly infected, instrumentation. The purpose of this study is
      to retrospectively review patients who underwent spinal surgery, investigate the
      rate of EDSSI, identify patient-related and surgery-related risk factors and to
      assess the effectiveness of continuous indwelling irrigation on the eradication
      of these infections. A total of 814 patients (319 women and 495 men) who
      underwent spinal surgery were enrolled. Mean age at the initial surgery was 57.4
      years old. Infections that penetrated the deep fascia within 1 month after the
      initial operation were considered as EDSSI. The rate of EDSSI, causal organisms,
      infection management and resolution were studied. Furthermore, we examined the
      patient-related and the operation-related risk factors. An overall incidence of
      EDSSI of 1.1% was found. In 177 patients with diabetes mellitus (DM), two
      patients (1.1%) developed EDSSI. In 28 patients receiving chronic haemodialysis
      (HD), two patients with infections (7.1%) were identified, which was
      statistically significantly greater than the other patient populations. Both
      operative time and intraoperative blood loss were significantly greater in
      patients with EDSSI than in non-infected patients. Furthermore, the rate of EDSSI
      in patients undergoing instrumented spinal fusion (3.8%) was significantly higher
      than that in the other patients. In the nine patients who developed EDSSI, the
      causal organisms were identified and treated by surgical debridement, antibiotic
      therapy and continuous indwelling surgical site irrigation. All infections
      resolved, and no recurrence has been observed at final follow-up. Removal of the
      instrumentation was required in only one patient. Based on our results, we
      believe that continuous surgical site irrigation is an effective adjunct in the
      surgical treatment for early SSI following spinal surgery.

PMID- 21848440
TI  - External ventricular drain infection: improved technique can reduce infection
      rates.
AB  - INTRODUCTION: The placement of external ventricular drain (EVD) is a common
      neurosurgical procedure to drain cerebrospinal fluid (CSF) in many acute
      neurosurgical conditions that disrupt the normal CSF absorption pathway.
      Infection is the primary complication with infection rates ranging between 0% and
      45%, and this is associated with significant morbidity and mortality, prolonged
      hospital stay and increased hospital costs.This article compares and discusses
      the differences in rates of EVD CSF infection between clinical neurosurgical
      practice and the infection rates in a group of research patients where EVDs were
      sampled frequently as part of the study. MATERIALS AND METHODS: Patients who had
      EVD placed were identified by review of theatre logs from 2005-2008. A
      retrospective case-note review was performed with the primary end point being
      those patients treated with intrathecal antibiotics. Patients within the research
      group were identified from established data and the same primary endpoint was
      used. A standard silicone catheter was the EVD used in both cohorts. Patients
      were excluded if the EVD was placed for diagnoses other than hydrocephalus
      associated with aneurysmal subarachnoid haemorrhage (SAH). RESULTS: Ninety-four
      patients had 156 EVDs placed within the clinical group, 49 patients were treated
      giving an infection rate within this group of 52.1% per patient and 31.4% per
      EVD. Thirty-nine patients had 39 EVDs placed within the research group, four
      patients were treated, the infection rate within this group was 10.3% per EVD, p
      = 0.0001. CONCLUSION: Sampling or irrigating ventricular drainage systems does
      not increase the risk of CNS infection providing the operator has appropriate
      experience and has used theatre standard aseptic technique.

PMID- 21848436
TI  - Stress risk factors and stress-related pathology: neuroplasticity, epigenetics
      and endophenotypes.
AB  - This paper highlights a symposium on stress risk factors and stress
      susceptibility, presented at the Neurobiology of Stress workshop in Boulder, CO,
      in June 2010. This symposium addressed factors linking stress plasticity and
      reactivity to stress pathology in animal models and in humans. Dr. J. Radley
      discussed studies demonstrating prefrontal cortical neuroplasticity and
      prefrontal control of hypothalamo-pituitary-adrenocortical axis function in rats,
      highlighting the emerging evidence of the critical role that this region plays in
      normal and pathological stress integration. Dr. M. Kabbaj summarized his studies
      of possible epigenetic mechanisms underlying behavioral differences in rat
      populations bred for differential stress reactivity. Dr. L. Jacobson described
      studies using a mouse model to explore the diverse actions of antidepressants in
      brain, suggesting mechanisms whereby antidepressants may be differentially
      effective in treating specific depression endophenotypes. Dr. R. Yehuda discussed
      the role of glucocorticoids in post-traumatic stress disorder (PTSD), indicating
      that low cortisol level may be a trait that predisposes the individual to
      development of the disorder. Furthermore, she presented evidence indicating that
      traumatic events can have transgenerational impact on cortisol reactivity and
      development of PTSD symptoms. Together, the symposium highlighted emerging themes
      regarding the role of brain reorganization, individual differences, and
      epigenetics in determining stress plasticity and pathology.

PMID- 21848441
TI  - Intracranial foreign body granuloma caused by dural tenting suture.
AB  - Our patient presented with a mass lesion mimicking a meningioma. The mass was
      resected, but pathological examination confirmed a foreign body granuloma, which
      was caused by silk fibres used as tenting sutures 8 years previously. Herein, we
      describe the case and review the neurosurgical literature on intracranial foreign
      body granulomas.

PMID- 21848442
TI  - Spontaneous regression of a third ventricle colloid cyst.
AB  - We present a case of a third ventricle colloid cyst in a 65-year-old patient who
      was managed conservatively with neuroimaging surveillance. To our surprise, the
      cyst underwent spontaneous regression 19 months after initial diagnosis. To our
      knowledge there has only been one similar case previously reported in Glasgow,
      United Kingdom in 2008.

PMID- 21848443
TI  - Impact of a combined diet and progressive exercise intervention for overweight
      and obese children: the B.E. H.I.P. study.
AB  - The Biochemical Evaluation of a Health Intervention Programme (B.E. H.I.P.)
      investigated the impact of progressive exercise intensity in overweight and obese
      children. A 5-month prospective randomized crossover design (X(A), immediate
      intervention; O(B), control group; X(B), delayed intervention, O(A),
      postintervention follow-up) with a 10-week health intervention programme was
      employed. The intervention utilized a progressive increase in high-intensity
      exercise (>= 75% maximum heart rate) and included 3 nutrition and 2 parent
      education sessions. Primary analysis was completed with (i) X(A) versus O(B) and
      (ii) all intervention participants (collapsed X(A) and X(B) = X(A)X(B)).
      Prepubertal overweight and obese male and female children (n = 27) between 5 and
      10 years of age were randomly allocated to X(A) (n = 16; 11 females; waist
      circumference = 80.0 +/- 10.6 cm) or O(B) (n = 11; 3 females; waist circumference
      = 76.6 +/- 7.5 cm). The primary variables were heart rate and percent fat mass.
      All variables, including body composition, habitual activity, and serum lipids,
      were repeatedly measured for up to a maximum of 7 time points. Energy expenditure
      was quantitatively measured throughout each exercise class (n = 20). A
      significantly longer time in the exercise sessions was spent in high-intensity
      (35.1%-60.0%) versus low- to moderate-intensity (64.9%-40.0%) exercise as the
      intervention progressed from the first to the last attended exercise class
      (Fisher exact test, p < 0.0001). The percent fat mass decreased in all
      intervention participants (-2.2%, p < 0.0001). X(A) had a greater slope decrease
      than O(B) for percent fat mass (p = 0.00051) and triglycerides (p = 0.0467). In
      conclusion, high-intensity exercise, within a comprehensive health programme that
      includes nutrition education, improved the lipid and physiological health
      profiles of obese children.

PMID- 21848444
TI  - Impact of integrating a physical activity counsellor into the primary health care
      team: physical activity and health outcomes of the Physical Activity Counselling
      randomized controlled trial.
AB  - The purpose of this paper was to report the physical activity and health outcomes
      results from the Physical Activity Counselling (PAC) trial. Patients (n = 120,
      mean age 47.3 +/- 11.1 years, 69.2% female) who reported less than 150 min of
      physical activity per week were recruited from a large community-based Canadian
      primary care practice. After receiving brief physical activity counselling from
      their provider, they were randomized to receive 6 additional patient-centered
      counselling sessions over 3 months from a physical activity counsellor (intensive
      counselling group; n = 61), or no further intervention (brief-counselling group;
      n = 59). Physical activity (self-reported and accelerometer) was measured every 6
      weeks up to 25 weeks (12 weeks postintervention). Quality of life was also
      assessed, and physical and metabolic outcomes were evaluated in a randomly
      selected subset of patients (33%). In the intent-to-treat analyses of covariance,
      the intensive-counselling group self-reported significantly higher levels of
      physical activity at 6 weeks (p = 0.009) and 13 weeks (p = 0.01). There were no
      differences in self-reported physical activity between the groups after the
      intervention in the follow-up period, nor was there any increase in accelerometer
      measured physical activity. Finally, the intensive-counselling patients showed
      greater decreases in percent body fat and total fat mass from 13 weeks to 25
      weeks. Results for physical activity depended on the method used, with positive
      short-term results with self-report and no effects with the accelerometers.
      Between-group differences were found for body composition in that the intensive
      counselling patients decreased more. A multisite randomized controlled trial with
      a longer intensive intervention and follow-up is warranted.

PMID- 21848445
TI  - Menstrual cycle and oral contraceptives' effects on growth hormone response to
      sprinting.
AB  - The present study examined the impact of the menstrual cycle and oral
      contraceptive (OC) use on the growth hormone response to non-motorized treadmill
      sprinting. Nine monophasic OC users (21.5 +/- 4.7 years old), and 8 normally
      menstruating women (NM; 21.4 +/- 2.9 years old) participated in the study. Each
      participant completed 2 main trials, each consisting of an all-out 30-s treadmill
      sprint. The NM group performed one trial in the midfollicular phase (NM
      follicular) and one in the midluteal phase (NM luteal); the OC group's trials
      occurred one week into the start of the pill-taking cycle and once during the
      week in which pills were not taken.Venous blood samples were analyzed for growth
      hormone, pH, lactate, glucose, and progesterone concentrations. Peak and mean
      power output did not differ between the groups or with menstrual phase, or
      between the OC-free and OC trials. Integrated growth hormone was greater in the
      OC group than in the NM group (p = 0.04) with no phase difference (p = 0.80, mean
      (SD); NM follicular: 421 (335) and NM luteal: 345 (304) vs. OC free: 737 (471)
      and OC: 758 (389) ug.L(-1).90 min(-1)). Blood lactate was higher in the OC group
      than in the NM group (p = 0.007) and, conversely, pH was lower in the OC group (p
      = 0.01). These results demonstrate that OC users who take high-androgenicity
      pills have a higher growth hormone response to sprint running than do normally
      menstruating women.

PMID- 21848446
TI  - Chromosomal localization of two novel repetitive sequences isolated from the
      Chenopodium quinoa Willd. genome.
AB  - The chromosomal organization of two novel repetitive DNA sequences isolated from
      the Chenopodium quinoa Willd. genome was analyzed across the genomes of selected
      Chenopodium species. Fluorescence in situ hybridization (FISH) analysis with the
      repetitive DNA clone 18-24J in the closely related allotetraploids C. quinoa and
      Chenopodium berlandieri Moq. (2n = 4x = 36) evidenced hybridization signals that
      were mainly present on 18 chromosomes; however, in the allohexaploid Chenopodium
      album L. (2n = 6x = 54), cross-hybridization was observed on all of the
      chromosomes. In situ hybridization with rRNA gene probes indicated that during
      the evolution of polyploidy, the chenopods lost some of their rDNA loci.
      Reprobing with rDNA indicated that in the subgenome labeled with 18-24J, one 35S
      rRNA locus and at least half of the 5S rDNA loci were present. A second analyzed
      sequence, 12-13P, localized exclusively in pericentromeric regions of each
      chromosome of C. quinoa and related species. The intensity of the FISH signals
      differed considerably among chromosomes. The pattern observed on C. quinoa
      chromosomes after FISH with 12-13P was very similar to GISH results, suggesting
      that the 12-13P sequence constitutes a major part of the repetitive DNA of C.
      quinoa.

PMID- 21848448
TI  - A split-face study using botulinum toxin type B to decrease facial erythema
      index.
AB  - INTRODUCTION: A reddish tone in facial skin is a common concern of patients who
      suffer from facial flushing. No studies have been conducted to date for
      evaluation of the effect of botulinum toxin type B (BTX-B) on facial flushing.
      MATERIALS AND METHOD: We evaluated the efficacy of BTX-B for improvement of
      facial flushing. Fifteen Korean subjects who complained of facial flushing were
      enrolled in this study. Patients were randomized to receive BTX-B injections on
      one side of the face, with the other side receiving saline control injections.
      Changes in skin tone were evaluated using an overall self-assessment and an
      objective mexameter. RESULT: After treatment, this mexameter demonstrated
      significant improvement of erythema at 8 weeks after injections on both sides.
      However, according to the change in erythema index measures between the two
      groups, the BTX-B injection side did not show a significant decrease in objective
      erythema, compared with the control side. Subjective satisfaction did not differ
      between the treated side and the control side. CONCLUSION: Although findings from
      this study suggest that BTX-B was ineffective in treatment of facial flushing, it
      is significant that, to the best of our knowledge, this is the first report on an
      investigator-initiated, randomized, split-face trial for evaluation of efficacy
      of BTX-B treatment for facial flushing.

PMID- 21848449
TI  - Development of an electronic web-based software for the management of colorectal
      cancer target referral patients.
AB  - In response to concern about lengthy waiting times for cancer treatment in the
      UK, the Department of Health introduced 'the colorectal cancer target referral
      scheme' to improve the referral process for suspected cancer. A user-centred web
      based intranet software was developed reflecting the core work of the multi
      disciplinary cancer team and the patient journey. The method used was primarily
      based on the concept of involving the end users (clinicians, nurses,
      administration staff) in the process of problem definition, software design,
      formative evaluation, development and implementation, from the very beginning, to
      ensure its relevance, functionality, and effectiveness. This software improved
      the interdisciplinary communication among doctors. All patients met the
      government waiting targets and proved to be a facilitative tool for audit,
      research and further prospective assessment of our service. Implementing a
      functional software design is mandatory for the management of target referral
      patients.

PMID- 21848450
TI  - Development of a chemotherapy regimen interaction database for the mobile
      internet: detecting interactions with psychotropics through OncoRx-MI.
AB  - INTRODUCTION: Cancer patients are at high risks of drug-drug interactions (DDIs).
      Clinicians need to know the magnitude of DDIs so as to better manage their
      patients' drug therapies. We have previously created a novel interaction database
      for oncology prescriptions (OncoRx). In this project, we leverage on 3G networks
      to further develop this database into an iPhone-specific application for the
      mobile internet (OncoRx-MI). METHODOLOGY: Data on anticancer drugs (ACDs),
      chemotherapy regimens (CRegs) and DDIs with psychotropics were compiled from
      various hardcopy and online resources, and published articles from PubMed, Scopus
      and Science Direct. The database and iPhone web documents were designed using
      Adobe Dreamweaver CS4 and associated with a combination of open-source
      programming scripts. RESULTS: OncoRx-MI currently detects over 5000 DDIs (69.3%
      pharmacokinetic, 30.7% pharmacodynamic) between 256 single-agent and combination
      CRegs with 51 psychotropic drugs. OncoRx-MI fits the iPhone screen configuration,
      and displays information regarding the regimen, pharmacokinetics of the drugs and
      detected DDIs in tabular format for improved usability. CONCLUSION: OncoRx-MI is
      the first mobile DDI application of its kind which detects interactions for
      combination CRegs. Future versions will include DDIs with other drug categories.
      Usability studies on its impact in clinical practice will also be carried out.

PMID- 21848451
TI  - Telematic integration of health data: a practicable contribution.
AB  - The patients' clinical and healthcare data should virtually be available
      everywhere, both to provide a more efficient and effective medical approach to
      their pathologies, as well as to make public healthcare decision makers able to
      verify the efficacy and efficiency of the adopted healthcare processes.
      Unfortunately, customised solutions adopted by many local Health Information
      Systems in Italy make it difficult to share the stored data outside their own
      environment. In the last years, worldwide initiatives have aimed to overcome such
      sharing limitation. An important issue during the passage towards standardised,
      integrated information systems is the possible loss of previously collected data.
      The herein presented project realises a suitable architecture able to guarantee
      reliable, automatic, user-transparent storing and retrieval of information from
      both modern and legacy systems. The technical and management solutions provided
      by the project avoid data loss and overlapping, and allow data integration and
      organisation suitable for data-mining and data-warehousing analysis.

PMID- 21848447
TI  - Mitochondrial dysfunction in genetic animal models of Parkinson's disease.
AB  - Mitochondria are highly dynamic, multifunctional organelles. Aside from their
      major role in energy metabolism, they are also crucial for many cellular
      processes including neurotransmission, synaptic maintenance, calcium homeostasis,
      cell death, and neuronal survival. SIGNIFICANCE: Increasing evidence supports a
      role for abnormal mitochondrial function in the molecular pathophysiology of
      Parkinson's disease (PD). For three decades we have known that mitochondrial
      toxins are capable of producing clinical parkinsonism in humans. PD is the most
      common neurodegenerative movement disorder that is characterized by the
      progressive loss of substantia nigra dopaminergic neurons leading to a deficiency
      of striatal dopamine. Although the neuropathology underlying the disease is well
      defined, it remains unclear why nigral dopaminergic neurons degenerate and die.
      RECENT ADVANCES: Most PD cases are idiopathic, but there are rare familial cases.
      Mutations in five genes are known to unambiguously cause monogenic familial PD:
      alpha-synuclein, parkin, DJ-1, PTEN-induced kinase 1 (PINK1), and leucine-rich
      repeat kinase 2 (LRRK2). These key molecular players are proteins of seemingly
      diverse function, but with potentially important roles in mitochondrial
      maintenance and function. Cell and animal-based genetic models have provided
      indispensable tools for understanding the molecular basis of PD, and have
      provided additional evidence implicating mitochondrial dysfunction as a primary
      pathogenic pathway leading to the demise of dopaminergic neurons in PD. CRITICAL
      ISSUES: Here, we critically discuss the evidence for mitochondrial dysfunction in
      genetic animal models of PD, and evaluate whether abnormal mitochondrial function
      represents a cause or consequence of disease pathogenesis. FUTURE DIRECTIONS:
      Mitochondria may represent a potential target for the development of disease
      modifying therapies.

PMID- 21848452
TI  - Testing the Technology Acceptance Model: HIV case managers' intention to use a
      continuity of care record with context-specific links.
AB  - OBJECTIVE: To assess the applicability of the Technology Acceptance Model (TAM)
      constructs in explaining HIV case managers' behavioural intention to use a
      continuity of care record (CCR) with context-specific links designed to meet
      their information needs. DESIGN: Data were collected from 94 case managers who
      provide care to persons living with HIV (PLWH) using an online survey comprising
      three components: (1) demographic information: age, gender, ethnicity, race,
      Internet usage and computer experience; (2) mock-up of CCR with context-specific
      links; and items related to TAM constructs. Data analysis included: principal
      components factor analysis (PCA), assessment of internal consistency reliability
      and univariate and multivariate analysis. RESULTS: PCA extracted three factors
      (Perceived Ease of Use, Perceived Usefulness and Perceived Barriers to Use),
      explained variance = 84.9%, Cronbach's alpha = 0.69-0.91. In a linear regression
      model, Perceived Ease of Use, Perceived Usefulness and Perceived Barriers to Use
      explained 43.6% (p < 0.001) of the variance in Behavioural Intention to use a CCR
      with context-specific links. CONCLUSION: Our study contributes to the evidence
      base regarding TAM in health care through expanding the type of professional
      surveyed, study setting and Health Information Technology assessed.

PMID- 21848454
TI  - Will the Food Safety Modernization Act help prevent outbreaks of foodborne
      illness?

PMID- 21848453
TI  - Moving beyond parity--mental health and addiction care under the ACA.

PMID- 21848455
TI  - Images in clinical medicine. An unusual cause of trigger finger.

PMID- 21848456
TI  - Interactive medical case. A problem in gestation.

PMID- 21848457
TI  - Pediatric HIV--a neglected disease?

PMID- 21848458
TI  - The doctor's dilemma--what is "appropriate" care?

PMID- 21848459
TI  - Complicated lives--taking the social history.

PMID- 21848460
TI  - Prevention of intraoperative awareness in a high-risk surgical population.
AB  - BACKGROUND: Unintended intraoperative awareness, which occurs when general
      anesthesia is not achieved or maintained, affects up to 1% of patients at high
      risk for this complication. We tested the hypothesis that a protocol
      incorporating the electroencephalogram-derived bispectral index (BIS) is superior
      to a protocol incorporating standard monitoring of end-tidal anesthetic-agent
      concentration (ETAC) for the prevention of awareness. METHODS: We conducted a
      prospective, randomized, evaluator-blinded trial at three medical centers. We
      randomly assigned 6041 patients at high risk for awareness to BIS-guided
      anesthesia (with an audible alert if the BIS value was <40 or >60, on a scale of
      0 to 100, with 0 indicating the suppression of detectable brain electrical
      activity and 100 indicating the awake state) or ETAC-guided anesthesia (with an
      audible alert if the ETAC was <0.7 or >1.3 minimum alveolar concentration). In
      addition to audible alerts, the protocols included structured education and
      checklists. Superiority of the BIS protocol was assessed with the use of a one
      sided Fisher's exact test. RESULTS: A total of 7 of 2861 patients (0.24%) in the
      BIS group, as compared with 2 of 2852 (0.07%) in the ETAC group, who were
      interviewed postoperatively had definite intraoperative awareness (a difference
      of 0.17 percentage points; 95% confidence interval [CI], -0.03 to 0.38; P=0.98).
      Thus, the superiority of the BIS protocol was not demonstrated. A total of 19
      cases of definite or possible intraoperative awareness (0.66%) occurred in the
      BIS group, as compared with 8 (0.28%) in the ETAC group (a difference of 0.38
      percentage points; 95% CI, 0.03 to 0.74; P=0.99), with the superiority of the BIS
      protocol again not demonstrated. There was no difference between the groups with
      respect to the amount of anesthesia administered or the rate of major
      postoperative adverse outcomes. CONCLUSIONS: The superiority of the BIS protocol
      was not established; contrary to expectations, fewer patients in the ETAC group
      than in the BIS group experienced awareness. (Funded by the Foundation for
      Anesthesia Education and Research and others; BAG-RECALL ClinicalTrials.gov
      number, NCT00682825.).

PMID- 21848462
TI  - Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis.
AB  - BACKGROUND: Generalized pustular psoriasis is a life-threatening disease of
      unknown cause. It is characterized by sudden, repeated episodes of high-grade
      fever, generalized rash, and disseminated pustules, with hyperleukocytosis and
      elevated serum levels of C-reactive protein, which may be associated with plaque
      type psoriasis. METHODS: We performed homozygosity mapping and direct sequencing
      in nine Tunisian multiplex families with autosomal recessive generalized pustular
      psoriasis. We assessed the effect of mutations on protein expression and
      conformation, stability, and function. RESULTS: We identified significant linkage
      to an interval of 1.2 megabases on chromosome 2q13-q14.1 and a homozygous
      missense mutation in IL36RN, encoding an interleukin-36-receptor antagonist
      (interleukin-36Ra), an antiinflammatory cytokine. This mutation predicts the
      substitution of a proline residue for leucine at amino acid position 27 (L27P).
      Homology-based structural modeling of human interleukin-36Ra suggests that the
      proline at position 27 affects both the stability of interleukin-36Ra and its
      interaction with its receptor, interleukin-1 receptor-like 2 (interleukin-1
      receptor-related protein 2). Biochemical analyses showed that the L27P variant
      was poorly expressed and less potent than the nonvariant interleukin-36Ra in
      inhibiting a cytokine-induced response in an interleukin-8 reporter assay,
      leading to enhanced production of inflammatory cytokines (interleukin-8 in
      particular) by keratinocytes from the patients. CONCLUSIONS: Aberrant interleukin
      36Ra structure and function lead to unregulated secretion of inflammatory
      cytokines and generalized pustular psoriasis. (Funded by Agence Nationale de la
      Recherche and Societe Francaise de Dermatologie.).

PMID- 21848461
TI  - Salmonella typhimurium infections associated with peanut products.
AB  - BACKGROUND: Contaminated food ingredients can affect multiple products, each
      distributed through various channels and consumed in multiple settings. Beginning
      in November 2008, we investigated a nationwide outbreak of salmonella infections.
      METHODS: A case was defined as laboratory-confirmed infection with the outbreak
      strain of Salmonella Typhimurium occurring between September 1, 2008, and April
      20, 2009. We conducted two case-control studies, product "trace-back," and
      environmental investigations. RESULTS: Among 714 case patients identified in 46
      states, 166 (23%) were hospitalized and 9 (1%) died. In study 1, illness was
      associated with eating any peanut butter (matched odds ratio, 2.5; 95% confidence
      interval [CI], 1.3 to 5.3), peanut butter-containing products (matched odds
      ratio, 2.2; 95% CI, 1.1 to 4.7), and frozen chicken products (matched odds ratio,
      4.6; 95% CI, 1.7 to 14.7). Investigations of focal clusters and single cases
      associated with nine institutions identified a single institutional brand of
      peanut butter (here called brand X) distributed to all facilities. In study 2,
      illness was associated with eating peanut butter outside the home (matched odds
      ratio, 3.9; 95% CI, 1.6 to 10.0) and two brands of peanut butter crackers (brand
      A: matched odds ratio, 17.2; 95% CI, 6.9 to 51.5; brand B: matched odds ratio,
      3.6; 95% CI, 1.3 to 9.8). Both cracker brands were made from brand X peanut
      paste. The outbreak strain was isolated from brand X peanut butter, brand A
      crackers, and 15 other products. A total of 3918 peanut butter-containing
      products were recalled between January 10 and April 29, 2009. CONCLUSIONS:
      Contaminated peanut butter and peanut products caused a nationwide salmonellosis
      outbreak. Ingredient-driven outbreaks are challenging to detect and may lead to
      widespread contamination of numerous food products.

PMID- 21848464
TI  - Development of antiretroviral drug resistance.

PMID- 21848463
TI  - Malpractice risk according to physician specialty.
AB  - BACKGROUND: Data are lacking on the proportion of physicians who face malpractice
      claims in a year, the size of those claims, and the cumulative career malpractice
      risk according to specialty. METHODS: We analyzed malpractice data from 1991
      through 2005 for all physicians who were covered by a large professional
      liability insurer with a nationwide client base (40,916 physicians and 233,738
      physician-years of coverage). For 25 specialties, we reported the proportion of
      physicians who had malpractice claims in a year, the proportion of claims leading
      to an indemnity payment (compensation paid to a plaintiff), and the size of
      indemnity payments. We estimated the cumulative risk of ever being sued among
      physicians in high- and low-risk specialties. RESULTS: Each year during the study
      period, 7.4% of all physicians had a malpractice claim, with 1.6% having a claim
      leading to a payment (i.e., 78% of all claims did not result in payments to
      claimants). The proportion of physicians facing a claim each year ranged from
      19.1% in neurosurgery, 18.9% in thoracic-cardiovascular surgery, and 15.3% in
      general surgery to 5.2% in family medicine, 3.1% in pediatrics, and 2.6% in
      psychiatry. The mean indemnity payment was $274,887, and the median was $111,749.
      Mean payments ranged from $117,832 for dermatology to $520,923 for pediatrics. It
      was estimated that by the age of 65 years, 75% of physicians in low-risk
      specialties had faced a malpractice claim, as compared with 99% of physicians in
      high-risk specialties. CONCLUSIONS: There is substantial variation in the
      likelihood of malpractice suits and the size of indemnity payments across
      specialties. The cumulative risk of facing a malpractice claim is high in all
      specialties, although most claims do not lead to payments to plaintiffs. (Funded
      by the RAND Institute for Civil Justice and the National Institute on Aging.).

PMID- 21848465
TI  - Images in clinical medicine. Scrotal calcinosis.

PMID- 21848466
TI  - Case records of the Massachusetts General Hospital. Case 25-2011. A 62-year-old
      woman with anemia and paraspinal masses.

PMID- 21848467
TI  - General anesthesia--minding the mind during surgery.

PMID- 21848468
TI  - Medical malpractice in the military.

PMID- 21848469
TI  - Alemtuzumab in kidney-transplant recipients.

PMID- 21848471
TI  - HLA-B*1502 screening and toxic effects of carbamazepine.

PMID- 21848472
TI  - HLA-B*1502 screening and toxic effects of carbamazepine.

PMID- 21848474
TI  - Vertebral fractures.

PMID- 21848475
TI  - Vertebral fractures.

PMID- 21848477
TI  - Bending the cost curve in cancer care.

PMID- 21848478
TI  - Bending the cost curve in cancer care.

PMID- 21848480
TI  - The parathyroid as a target for radiation damage.

PMID- 21848481
TI  - Candesartan in the treatment of hypertension: what have we learnt in the last
      decade?
AB  - INTRODUCTION: Although all of the first-line antihypertensive drugs effectively
      reduce blood pressure, there are some conditions that may favor the use of
      angiotensin receptor blockers over others, such as left ventricular hypertrophy,
      microalbuminuria, renal dysfunction, diabetes, or metabolic syndrome, among
      others. AREAS COVERED: This manuscript reviewed the data supporting the use of
      candesartan cilexetil in hypertensive population with a special focus on its
      efficacy and safety. For this purpose, a search on MEDLINE and EMBASE databases
      was performed. The MEDLINE and EMBASE search included both medical subject
      headings (MeSH) and keywords including: candesartan OR angiotensin receptor
      blockers OR renin angiotensin system AND hypertension treatment. References of
      the retrieved articles were also screened for additional studies. There were no
      language restrictions. EXPERT OPINION: Candesartan, a long-acting angiotensin
      receptor antagonist, has been shown to be an effective and well-tolerated therapy
      in the entire spectrum of hypertensive patients, including those at higher risk,
      such as those with diabetes, metabolic syndrome, left ventricular hypertrophy, or
      microalbuminuria.

PMID- 21848482
TI  - Screening for pre-eclampsia: a systematic review of tests combining uterine
      artery Doppler with other markers.
AB  - AIMS: To perform a systematic review of screening for pre-eclampsia (PE) with the
      combination of uterine artery Doppler (UAD), maternal history, mean arterial
      pressure and/or maternal serum markers. METHODS: We identified eligible studies
      through a search of Medline, and, for each included study, we assessed the risk
      of bias and extracted relevant data. We reported the performance of screening
      tests according to the target population (low- or high-risk), the trimester of
      screening (first and/or second) and the subset of PE screened for (early and
      late). RESULTS: Several tests provided moderate or convincing prediction of early
      PE, but screening for late PE was poor. Although UAD is more accurate in the
      second trimester, we found encouraging results for first-trimester screening when
      it was combined with other markers. Performance of screening was consistently
      lower in populations with risk factors for PE in the maternal history.
      CONCLUSIONS: We present encouraging results for the prediction of early PE, even
      in the first trimester of pregnancy. The different performance of tests in
      screening for early vs. late PE, and of low- vs. high-risk populations, supports
      the concept that PE is a heterogeneous disease.

PMID- 21848484
TI  - Triterpenoids from Arctium lappa.
AB  - Phytochemical investigation of the leaves of Arctium lappa led to the isolation
      of two triterpenoids, characterised by NMR, IR and MS as 3alpha-hydroxylanosta
      5,15-diene and 3alpha-acetoxy-hop-22(29)-ene. 3alpha-hydroxylanosta-5,15-diene is
      a new triterpenoid and is isolated for the first time from this genus.

PMID- 21848485
TI  - Engaging in cultural activities compensates for educational differences in
      cognitive abilities.
AB  - The goal of the current project was to examine whether engagement in
      intellectual/cultural activities explains the long-term effects of education on
      cognitive abilities throughout adulthood, and whether it compensates for
      educational differences in cognitive abilities throughout adulthood. Participants
      between 18 and 96 years of age completed a comprehensive questionnaire about
      intellectual/cultural activities that they participated in and performed a wide
      variety of cognitive tests. There were no mediation effects of engagement in
      intellectual/cultural activities on the relationship between education and
      cognitive functioning. In contrast, engagement in intellectual/cultural
      activities was found to moderate the relations between education and the level of
      fluid ability, working memory, speed of processing, and episodic memory. Findings
      suggest that the risk of cognitive decline in people with less education can be
      reduced via engagement in intellectual and cultural activities throughout
      adulthood.

PMID- 21848483
TI  - Placental lesions associated with maternal underperfusion are more frequent in
      early-onset than in late-onset preeclampsia.
AB  - OBJECTIVE: Preeclampsia (PE) has been classified into early- and late-onset
      disease. These two phenotypic variants of PE have been proposed to have a
      different pathophysiology. However, the gestational age cut-off to define "early"
      vs. "late" PE has varied among studies. The objective of this investigation was
      to determine the prevalence of lesions consistent with maternal underperfusion of
      the placenta in patients with PE as a function of gestational age. STUDY DESIGN:
      A nested case-control study of 8307 singleton pregnant women who deliver after 20
      weeks of gestation was constructed based on a cohort. Cases were defined as those
      with PE (n=910); controls were pregnant women who did not have a hypertensive
      disorder in pregnancy (n=7397). The frequency of maternal underperfusion of the
      placenta (according to the criteria of the Society for Pediatric Pathology) was
      compared between the two groups. Logistic regression was used for analysis.
      Estimated relative risks (RRs) were calculated from odds ratios. RESULTS: 1) The
      prevalence of lesions consistent with maternal underperfusion was higher in
      patients with PE than in the control group [43.3% vs. 15.9%, unadjusted odds
      ratio 4.0 (95% CI 3.5-4.7); P<0.001]; 2) the estimated RR of maternal
      underperfusion lesions in PE was higher than in the control group [RR=2.8 (95% CI
      2.5-3.0)]; 3) the lower the gestational age at delivery, the higher the RR for
      these lesions; 4) early-onset PE, regardless of the gestational age used to
      define it (<32, 33, 34, 35 or 37 weeks) had a significantly higher frequency of
      placental lesions consistent with maternal underperfusion than late-onset PE
      (P<0.001 for all). CONCLUSIONS: 1) The earlier the gestational age of
      preeclampsia at delivery, the higher the frequency of placental lesions
      consistent with maternal underperfusion; 2) our data suggest that demonstrable
      placental involvement as determined by pathologic examination differs in early-
      and late-onset preeclampsia; and 3) this phenomenon appears to be a continuum,
      and we could not identify a clear and unambiguous gestational age at which
      lesions consistent with underperfusion would not be present.

PMID- 21848486
TI  - In vitro and in vivo effects of Houttuynia cordata on infectious bronchitis
      virus.
AB  - Avian infectious bronchitis virus (IBV), a coronavirus, causes infectious
      bronchitis leading to enormous economic loss in the poultry industry worldwide.
      Houttuynia cordata (Saururaceae) (HC) is a traditional Chinese medicine used in
      China. In the present study, the effect of HC on cell infection by IBV was
      determined using plaque assay and reverse transcription-polymerase chain
      reaction. The inhibitory effect of HC on IBV infection in ovo and in vivo was
      analysed using specific pathogen free (SPF) chicken embryos and chickens.
      Moreover, the effect of HC on cell apoptosis induced by IBV was investigated.
      Results showed that HC had more than 90% inhibition rate against IBV infection in
      Vero cells and chicken embryo kidney cells, and decreased more than 90% apoptotic
      cells caused by IBV. HC fully protected the SPF embryos, and had more than 50%
      protection rate in SPF chickens, against IBV challenge.

PMID- 21848487
TI  - Evaluation of trace element contents in Swertia paniculata Wall..
AB  - Important mineral elements (Fe, Zn, Mn, Cu, Co, Na, K, Ca and Li) were determined
      in the leaves and roots of Swertia paniculata collected from three different
      altitudes in three seasons using atomic absorption spectroscopy. The highest
      concentrations of Zn, Cu, Mn, Fe, Co, Na, K, Ca and Li were found to be 193.0 +/-
      5.6, 26.0 +/- 7.6, 303.0 +/- 8.5, 1507.0 +/- 2.5, 88.0 +/- 1.2, 345.0 +/- 1.2,
      11622.0 +/- 6.4, 3461.0 +/- 3.5 and 48.0 +/- 4.5 mg kg(-1), respectively. The
      overall concentration of K was found to be the highest, whereas the level of Cu
      was the lowest. The concentrations of Cu and Li were quite low in all samples,
      whereas Zn, Mn, Co and Na were found in moderate concentration and K, Ca and Fe
      were found in very high concentrations in all the samples tested.

PMID- 21848488
TI  - Selected sociocultural correlates of physical activity among African-American
      adults.
AB  - OBJECTIVE: Previous studies have identified several factors to be associated with
      physical activity (PA) among African-Americans, e.g., demographic and health
      related characteristics. Formative studies suggest a link between sociocultural
      factors and PA among ethnic minorities; yet, it is unclear whether these factors
      play a role in PA among African-Americans. This paper explores the association of
      selected sociocultural characteristics with self-reported PA by gender among
      African-American adults, taking into account demographic and health-related
      characteristics. DESIGN: Data from the baseline survey of a colorectal cancer
      communication intervention trial were used. Participants included 446 African
      American men and women, aged 45-75 years. Self-report data were collected on
      demographics, health-related characteristics, selected sociocultural constructs
      (e.g., ethnic identity, religiosity, collectivism, and medical mistrust), and PA.
      PA was categorized as meeting or not meeting recommended levels; recommended
      levels were defined as participating in vigorous PA for 20 minutes/day for at
      least three days/week or moderate PA for 30 minutes/day for at least five
      days/week or a minimum of 600 MET-minutes/week in at least five days. Chi-square
      and multivariate logistic regression models were used to characterize the
      association between the selected sociocultural constructs and PA among men and
      women, after adjusting for demographic and health-related characteristics.
      RESULTS: Most participants reported some PA but only 59% were found to be meeting
      recommended levels. Univariate analyses revealed that high collectivist attitudes
      were associated with meeting recommended PA (OR = 1.74), particularly for women
      (OR = 1.81). In multivariate analyses, high collectivist attitudes were
      significantly associated with meeting PA recommendations among men (OR = 1.87);
      while high religiosity and high collectivism were significant among women (OR =
      1.87 and 1.85, respectively). CONCLUSIONS: Few of the selected sociocultural
      characteristics were found to be associated with meeting recommended PA levels.
      Further study is needed to understand the association of these characteristics
      with PA among African-Americans.

PMID- 21848489
TI  - Effect of andrographolide on cysteamine-induced duodenal ulcer in rats.
AB  - The aim of this study was to evaluate the gastroprotective efficacy of
      andrographolide isolated from Andrographis paniculata in rats induced with
      duodenal ulcers. Duodenal ulcers were induced by cysteamine administration in
      rats pretreated with 3 mg kg-1 BW day-1 of andrographolide for 30 days. Ulcer
      score, myeloperoxidase activity, TBARS level, GSH/GSSG ratio and enzyme
      antioxidants were measured in the duodenal tissue. Brush border and basolateral
      membranes were isolated to assay sucrase, maltase, alkaline phosphatase and total
      ATPases. Ulcer score was significantly minimised in rats pretreated with
      andrographolide. Elevation in myeloperoxidase and TBARS levels were found to be
      minimised significantly due to andrographolide treatment. Membrane-bound enzyme
      activities and the thiol redox status of glutathione were significantly
      maintained in duodenal mucosa of rats that received andrographolide. This study
      reveals that the major component of A. paniculata, andrographolide, has potent
      antiulcer properties that are most likely caused by minimising inflammatory
      changes, counteracting free radical formation and maintaining the thiol redox
      status in the duodenum.

PMID- 21848490
TI  - Two new lupene-type triterpenoids from the roots of Liquidambar formosana.
AB  - Two new lupene-type triterpenoids, 3beta,6beta-dihydroxylup-20(29)-en-28-oic acid
      beta-glucopyranosyl ester (1) and 2alpha-acetoxyl-3beta,6beta-dihydroxylup-20(29)
      en-28-oic acid beta-glucopyranosyl ester (2), along with 18 known compounds, were
      isolated from Liquidambar formosana. The structures were elucidated on the basis
      of spectroscopic methods, including UV, IR, ESIMS, 1D- and 2D-NMR experiments, as
      well as by comparison of the spectral data with those of related compounds.

PMID- 21848491
TI  - A new triterpene from Salvia xanthocheila Boiss.
AB  - From the chloroform extract of the aerial parts of Salvia xanthocheila, one new
      triterpene, together with two known diterpenes, two known flavonoids and a
      phytosterol was isolated. On the basis of comprehensive spectroscopic analyses,
      including electron ionisation mass spectra, 1H-NMR, 13C-NMR, 1-D nuclear
      Overhauser effect, distortionless enchancement by polarisation transfer, H,H
      correlation spectroscopy, heteronuclear multiple quantum coherence, rotating
      frame Overhauser enhancement spectroscopy spectra and comparison with spectral
      data of known compounds, the structure of new compounds was established as
      1beta,3beta-dihydroxy-olean-9(11),12-dienyl (1). The five known compounds (2-6)
      were 7alpha-acetoxyroyleanone, taxodione, salvigenin, apigenin-7,4'-dimethyl
      ether and beta-sitosterol, respectively. These known structures are isolated from
      the aerial parts of S. xanthocheila for the first time.

PMID- 21848492
TI  - Nephroprotective and antioxidant activities of Salacia oblonga on acetaminophen
      induced toxicity in rats.
AB  - Salacia oblonga, a woody climbing plant belonging to the family Celastaceae, is
      widely distributed in India and other southeast Asian countries. The genus
      Salacia have been used particularly for the treatment of diabetes, obesity,
      gonorrhoea, rheumatism, pruritus and asthma. Acetaminophen (APAP), used as an
      analgesic drug, produces liver and kidney necrosis in mammals at high doses. The
      aim of this study was to investigate the nephroprotective and antioxidant
      activities of the ethanol extract of Salacia oblonga (EESO) at the two dose
      levels of 250 and 500 mg/kg bw on APAP-induced toxicity in rats. The results
      showed that APAP significantly increases the levels of serum urea, creatinine,
      and reduces levels of uric acid concentration. The EESO reduces these by
      increasing anti-oxidative responses as assessed by biochemical and
      histopathological parameters. In conclusion, our results suggest that the EESO
      possesses nephroprotective and antioxidant effects against APAP-induced
      nephrotoxicity in rats.

PMID- 21848493
TI  - A mixed treatment comparison of the short-term efficacy of biologic disease
      modifying anti-rheumatic drugs in established rheumatoid arthritis.
AB  - BACKGROUND: The short-term efficacy of biological disease modifying anti
      rheumatic drugs (bDMARDs) for the treatment of established moderate to severe
      rheumatoid arthritis (RA) has been demonstrated by various randomized placebo or
      active treatment controlled trials. However, there is a lack of direct comparison
      of these agents. SCOPE: To compare the short-term efficacy of nine bDMARDs -
      abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab,
      rituximab and tocilizumab - in patients with established RA. FINDINGS: A
      systematic review was conducted to obtain all available efficacy data for each
      included bDMARD. Medline, EMBASE, and Cochrane clinical trials were searched for
      trials in patients with RA. Twenty-seven trials were retrieved from a systematic
      literature search and included in the meta-analysis. Mixed treatment comparison
      (MTC) techniques were used to perform indirect comparisons. Analyses were
      conducted to estimate the odds ratio of an ACR20, ACR50, and ACR70 response at
      approximately six months if treated with a bDMARD compared with placebo or
      methotrexate. Between-drug comparisons were also made. The analyses were
      performed including recommended doses only (as per the product information). All
      drugs except anakinra and golimumab demonstrated a statistically significant
      advantage compared to control treatment for ACR20 responses. The between-drug
      comparisons revealed a statistically significant advantage for certolizumab
      compared to most bDMARDs for ACR20, ACR50 and ACR70 response and for etanercept
      versus adalimumab and anakinra for ACR20 and ACR50 response, as well as a
      statistically significant advantage for tocilizumab versus anakinra for ACR50
      response. CONCLUSION: The analyses, using MTC of efficacy of nine bDMARDs suggest
      that treatment with anakinra is inferior to other bDMARDs and that etanercept and
      certolizumab may be more effective than other bDMARDs. There are some limitations
      of our analyses due to MTC assumptions, variations in trial design and the fact
      that only ACR outcomes at six months were included.

PMID- 21848494
TI  - On the action and mechanism of withaferin-A from Withania somnifera, a novel and
      potent melanin dispersing agent in frog melanophores.
AB  - The present work was carried out to determine the effects of lyophilized root
      extracts of Withania somnifera along with pure withaferin-A, on the isolated skin
      melanophores of frog, Rana tigerina which are disguised type of smooth muscle
      cells and offer excellent in vitro opportunities for studying the effects of
      pharmacological and pharmaceutical agents. The lyophilized extract of W.
      somnifera and its active ingredient withaferin-A induced powerful dose-dependent
      physiologically significant melanin dispersal effects in the isolated skin
      melanophores of R. tigerina, which were completely blocked by atropine as well as
      hyoscine. The per se melanin dispersal effects of lyophilized extracts of W.
      somnifera and its active ingredient withaferin-A got highly potentiated by
      neostigmine. It appears that the melanin dispersal effects of the extracts of W.
      somnifera and withaferin-A is mediated by cholino-muscarinic like receptors
      having similar properties.

PMID- 21848496
TI  - Vasomotor symptoms and cardiovascular disease risk.
AB  - Although the exact etiology of hot flushes and night sweats has not been fully
      clarified, the intriguing question whether vasomotor symptoms (VMS) are markers
      of coronary artery disease risk has been evaluated in several studies. Surrogate
      metabolic and hemodynamic parameters point at adverse alterations in flushers,
      but the results related to clinical endpoints are not unidirectional. Recent
      relevant data come from the Women's Health Initiative (WHI) observational study
      (60 000 women, mean age 63 years, mean follow-up period 10 years). Women with VMS
      only at onset of menopause but not at enrollment to the WHI study had a modest,
      yet significant decreased risk of stroke, total cardiovascular disease events,
      and all-cause mortality, compared with women having no VMS. Contrarily, women
      with late VMS (reported at enrollment to the study but not at onset of menopause)
      had an increased risk in the above-mentioned parameters. There was no interaction
      between hormone use and VMS in this respect. This mini-review, which summarizes
      the relevant data, shows that hot flushes seem to be a marker for physiological
      alterations that could be associated with cardiovascular disease.

PMID- 21848495
TI  - Menopausal hot flushes and night sweats: where are we now?
AB  - OBJECTIVE: An overview of the current knowledge on the etiology and treatment of
      vasomotor symptoms in postmenopausal women. MATERIALS AND METHODS: Acknowledged
      experts in the field contributed a brief assessment of their areas of interest
      which were combined and edited into the final manuscript. RESULTS: Women around
      the world experience vasomotor symptoms as they enter and complete the menopause
      transition. Vasomotor symptoms, specifically hot flushes, are caused by a
      narrowing of the thermoneutral zone in the brain. This effect, although related
      to estrogen withdrawal, is most likely related to changes in central nervous
      system neurotransmitters. Peripheral vascular reactivity is also altered in
      symptomatic women. Estrogen replacement therapy is the most effective treatment
      for hot flushes. Of the other interventions investigated, selective serotonin and
      selective norepinephrine reuptake inhibitors and gabapentin show efficacy greater
      than placebo. Objective monitoring of hot flushes indicates a robust improvement
      with hormone replacement therapy but little to no change with placebo. These data
      suggest that the subjective assessment of responses to therapy for vasomotor
      symptom results in inaccurate data. Hot flushes have recently been associated
      with increased cardiovascular risks and a lower incidence of breast cancer, but
      these data require confirmation. CONCLUSIONS: Vasomotor symptoms are experienced
      by women of all ethnic groups. They are caused by changes in the central nervous
      system associated with estrogen withdrawal and are best treated with estrogen
      replacement therapy. Objective monitoring of hot flushes indicates that placebo
      has little to no effect on their improvement. Subjective assessments of hot
      flushes in clinical trials may be inaccurate based on objective measurement of
      the frequency of hot flushes. Based on preliminary reports, women experiencing
      hot flushes have an increased risk of cardiovascular disease and a reduced
      incidence of breast cancer.

PMID- 21848497
TI  - Clinical usefulness of a low-dose maintenance therapy with transdermal estradiol
      gel in Japanese women with estrogen deficiency symptoms.
AB  - OBJECTIVES: To determine the efficacy and safety of low-dose maintenance therapy
      with transdermal estradiol (E2) gel in Japanese women with climacteric disorder
      and estrogen deficiency symptoms. METHODS: Women (n = 209) aged 37-59 years who
      had climacteric disorder or estrogen deficiency symptoms received a standard dose
      of transdermal E2 gel (1.8 g/day, containing E2 1.08 mg/day) for 8 weeks as
      induction treatment. A total of 177 women in whom the number of daily hot flushes
      had decreased to less than one-third of the baseline value (marked improvement)
      at week 8 were double-blindly randomized to receive low-dose E2 (n = 88, 0.9
      g/day, containing E2 0.54 mg/day) or E2-free placebo (n = 89) for 16 weeks.
      RESULTS: Improvement rates in the number of daily hot flushes at the final
      evaluation (primary endpoint) in the low-dose E2 group (marked 90.8%, moderate
      6.9%, mild 1.1%, no change 1.1%, worsening 0%) were significantly greater than in
      the placebo group (marked 77.0%, moderate 10.3%, mild 4.6%, no change 2.3%,
      worsening 5.7%) (p = 0.0097), showing an inhibitive effect on the flare-up of
      climacteric symptoms. The incidence of treatment-related adverse events in the
      low-dose group (21.6%) was similar to that in the placebo (22.5%) but was lower
      than that in the standard-dose treatment (32.5%). CONCLUSIONS: Low-dose
      maintenance therapy that was half the standard dose of transdermal E2 gel (0.9
      g/day) applied to women who had achieved marked improvement in the number of hot
      flushes at the standard dose (1.8 g/day) was demonstrated to be effective
      (inhibition of recurrence) and safe for the treatment of climacteric disorder and
      estrogen deficiency symptoms.

PMID- 21848498
TI  - Plasticity changes in adult metabolic homeostasis and tissue oxidative stress:
      neonatal programming by corticosterone and melatonin as deprogrammer.
AB  - OBJECTIVE: To evaluate the long-term plasticity changes induced by neonatal
      corticosterone programming on adult metabolic status and the deprogramming effect
      of melatonin. METHODS: Male and female Wistar rats were maintained under standard
      conditions and when mated females delivered pups, neonates of both sexes were
      separated and equal number of pups was assigned to lactating mothers. Pups
      treated with saline, corticosterone or a combination of corticosterone and
      melatonin from PND 2 to PND 14, were maintained until 120 days of age. Various
      serum and tissue parameters pertaining to glycaemic regulation, dyslipidemia,
      hepatic and renal distress and oxidative stress were analyzed in adult rats.
      RESULTS: Neonatal corticosterone exposure induced dyslipidemia, increased fed and
      fasting glucose levels, insulin resistance, lipid peroxidation, serum levels of
      insulin, corticosterone and hepatic and renal dysfunction markers and decreased
      the levels of enzymatic and non-enzymatic antioxidants, relatively more in males.
      Melatonin proved as an effective deprogrammer of corticosterone induced
      plasticity changes. CONCLUSIONS: Neonatal corticosterone exposure induces long
      lasting effects on adult physiology and metabolism. Concurrent treatment with
      melatonin effectively deprograms the changes.

PMID- 21848499
TI  - Monitoring of mycophenolic acid and kidney function during combined
      immunosuppressive therapy.
AB  - BACKGROUND: Mycophenolic acid (MPA), a selective inhibitor of lymphocyte
      proliferation, has lately been used to improve renal function and prolong graft
      survival in renal transplanted patients. Still, there is no consensus considering
      the recommended dosing and the therapeutic range of MPA. METHODS: To estimate the
      safe therapeutic range of MPA, its plasma level and indicators of kidney function
      were measured in 216 patients (138 male, 78 female, age 46 +/- 12 years) 67 +/-
      46 months after transplantation. Besides MPA, patients received cyclosporine
      (Group A, n=122) or tacrolimus (Group B, n=77). Seventeen patients (Group C) were
      treated with MPA in combination with everolimus or sirolimus. Plasma MPA was
      measured by enzyme inhibition assay. RESULTS: In the whole study group MPA level
      increased with the dose of MPA (p=0.013). MPA level was below the therapeutic
      range in 40% (Group A) and 45% (Group B) of patients, respectively. MPA was 1.9
      +/- 1.56 mg/L in Group A, 2.4 +/- 1.69 mg/L in Group B. In Group A MPA level
      increased and cyclosporine decreased with the progress of renal disease.
      CONCLUSIONS: Increasing MPA/cyclosporine ratio at more severe stages of chronic
      kidney disease was tolerable for the patients and rejection could be avoided.
      Tubular damage detected by urinary N-acetyl-beta-D-glucosaminidase did not
      correlate with the MPA level.

PMID- 21848500
TI  - alpha-Tocopherol supplementation avoids apoptosis in the anal sphincter.
AB  - PURPOSE: To analyze the influence of alpha-tocopherol supplementation on the
      levels of oxidative stress and apoptosis rates in the anal sphincter induced by
      orchiectomy in rats. METHODS: Forty male Wistar rats weighing 250-300 g, were
      divided into four groups and sacrificed 8 weeks after: I- Control: sham; II-
      Orchiectomy: bilateral orchiectomy; III- Pre Orchiectomy Tocopherol: alpha
      tocopherol supplementation for 4 weeks preceding bilateral orchiectomy; IV-
      Orchiectomy Full Tocopherol: alpha-tocopherol supplementation for 4 weeks before
      and 8 weeks after bilateral orchiectomy. The anal sphincter was analyzed
      stereologically to evaluate the density of collagen and the muscle fibers. The
      oxidative stress and the apoptosis were determined with 8-isprostane and caspase
      3, respectively. RESULTS: The collagen fibers concentration was statistically
      greater in Orchiectomy group than the others. The muscle fibers concentration was
      higher in Control and Orchiectomy Full Tocopherol than Orchiectomy and Pre
      Orchiectomy Tocopherol groups. Orchiectomy group showed higher 8-isoprostane
      concentrations compared to the other groups (p < 0.0003). Pre Orchiectomy
      Tocopherol and Orchiectomy Full Tocopherol groups presented caspase-3 levels
      lower than the Orchiectomy group (0.0072). CONCLUSION: Vitamin supplementation
      with alpha-tocopherol for 12 weeks had the highest protection against bilateral
      orchiectomy generation of reactive oxygen species as well as apoptosis in the
      muscle fibers of the anal sphincter of rats.

PMID- 21848501
TI  - Establishing an evaluation scale for the perception of quality of life related to
      relapsing-remitting forms of multiple sclerosis and feasibility study.
AB  - Relapses are particularly stressful for patients with multiple sclerosis (MS).
      The impact of relapses on the quality of life (QoL) of patients has been
      described in the literature. Several QoL scales have already been validated for
      MS. However, none of them focuses specifically on how patients perceive relapse
      periods. The objective of this research was to establish a self-questionnaire to
      evaluate QoL related to MS and relapses: the PERSEPP scale. This scale is based
      on individual semidirective interviews with patients with a relapsing-remitting
      form of MS, health workers, and focus groups. The thematic content analysis of
      these interviews allowed us to obtain 574 items related to various dimensions of
      QoL. After selecting items in several stages, we drew up the PERSEPP scale with
      37 items and five additional modules. A preliminary feasibility study was
      conducted with 40 patients to assess the PERSEPP scale. The feasibility study
      showed a good acceptability and a good understanding of the items of the PERSEPP
      scale. This article deals with the selection of items and the acceptability
      study. Psychometric validation of this scale, involving 305 patients, is
      currently in progress in various hospitals in France.

PMID- 21848502
TI  - Promoting effects of chemical permeation enhancers on insulin permeation across
      TR146 cell model of buccal epithelium in vitro.
AB  - To find potential enhancers for facilitating the buccal delivery of insulin, a
      TR146 cell-culture model of buccal epithelium, cultured on commercially available
      insert plates, was used to evaluate the permeability-enhancing effects of several
      traditional and new types of chemical enhancers, including N-acetyl-L-cysteine
      (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione
      (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan
      2-one (Azone), and soybean lecithin (SPC) (50 and 10 MUg/mL respectively).
      Permeability studies were performed to determine the enhancing effects of these
      compounds on insulin permeation across the cell-culture model. The enhancing
      effects of the enhancers were assessed by calculating the apparent permeability
      coefficients and enhancement ratio. Cytotoxicity of the permeation enhancers at
      different concentrations was investigated by using the methylthiazolydiphenyl
      tetrazolium bromide (MTT) assay. Results showed that 50 MUg/mL of NAC, SDC, GSH,
      CS, Arg, Azone, SPC, SNP, and 10 MUg/mL of SNP had a significant enhancing effect
      on promoting the transport of insulin across the TR146 cell model. MTT assays
      showed that 50 MUg/mL of Gln, Azone, SDC, SNP, Arg, 10 MUg/mL SDC, and Arg had
      obvious toxic effects on TR146 cells. Therefore, NAC, GSH, CS, SPC, and SNP
      appear to be safe, effective permeability enhancers that promote the transport of
      insulin across the TR146 cell-culture model of buccal epithelium and may be
      potential enhancers for buccal delivery of insulin with both low toxicity and
      high efficiency.

PMID- 21848503
TI  - Cadmium inhibits the differentiation of 3T3-L1 preadipocyte through the
      C/EBPalpha and PPARgamma pathways.
AB  - Cadmium, a well-known toxic heavy metal, affects cellular physiology by
      disturbing cellular signaling pathways. We investigate the effect of cadmium on
      cellular differentiation using 3T3-L1 preadipocyte cell lines as an in vitro
      model. Here, it was shown that cadmium (3 MUM) significantly decreased both
      glycerol-3-phosphate dehydrogenase (GPDH) activity and lipid accumulation of
      differentiating 3T3-L1 cells in a dose-dependent manner. In addition, inhibitory
      action of cadmium on differentiating 3T3-L1 cells was effective only at the
      initial stage of 3T3-L1 preadipocyte differentiation. Western blot analysis
      revealed that cadmium suppressed the expression of CCAAT/enhancer-binding protein
      alpha (C/EBPalpha) and peroxisome proliferator-activator receptor gamma
      (PPARgamma) proteins, key transcriptional activators for adipogenesis, in a dose
      dependent manner. These results suggest that the inhibitory effects of cadmium on
      3T3-L1 preadipocyte differentiation, as indicated by a decrease in GPDH activity
      and lipid accumulation, a marker of adipogenesis, appeared to be mediated through
      the downregulated expression of C/EBPalpha and PPARgamma proteins.

PMID- 21848504
TI  - mRNA expression levels of the biological factors uPAR, uPAR-del4/5, and rab31,
      displaying prognostic value in breast cancer, are not clinically relevant in
      advanced ovarian cancer.
AB  - High tumor tissue mRNA expression of the tumor biological factors uPAR, uPAR
      del4/5, or rab31 is associated with shorter distant metastasis-free and overall
      survival in breast cancer patients. To evaluate whether these factors are also
      clinically relevant in ovarian cancer, we quantified the respective mRNA levels
      in primary tumor tissue of advanced ovarian cancer patients (n=103) and evaluated
      their association with clinicopathological parameters and patients' prognosis.
      mRNA expression levels of all three markers did not show any significant
      association with overall or progression-free survival, demonstrating that these
      factors have no prognostic value in advanced ovarian cancer.

PMID- 21848505
TI  - Iron-catalyzed oxidation of Trp residues in low-density lipoprotein.
AB  - The mechanisms of oxidation of low-density lipoproteins (LDLs) are not well
      defined, but epidemiological and experimental studies suggest that iron-catalyzed
      processes may contribute to atherogenesis. The aim of this study was to test the
      hypothesis that iron-catalyzed oxidations of LDLs in vitro produce diagnostic
      biomarkers of oxidation of the apolipoprotein that could be applied to studies in
      vivo. LDLs were oxidized in the presence of Fe2+, EDTA, and ascorbic acid for up
      to 40 h. Following delipidation and trypsin digestion, the peptides were
      separated by HPLC, with four peaks detected at 365 nm, whereas none were observed
      in peptides from unoxidized LDLs. The peptides were identified by MALDI-QTOF mass
      spectrometry as IVQILP(W+4) EQNEQVK, IYSL(W+4)EHSTK, FEGLQE(W+4)EGK, and
      YH(W+4)EHTGLTLR, with (W+4) rather than the W residues of the unoxidized protein.
      The mass gains (+4 increase in m/z in tryptophan, W) and absorbance at 365 nm
      indicate kynurenines, which were trypsin-releasable peptides that are on the
      surface of LDL particles. All four peptides thus characterized share the sequence
      of WE. The preferential oxidation of W residues in WE sequences suggest
      contributions from the C-proximate glutamate residues in chelation of the iron
      species, thereby influencing site selectivities of oxidation. These kynurenine
      containing peptides might serve as biomarkers of iron-mediated oxidations in
      vivo.

PMID- 21848506
TI  - Conformational changes of the chaperone SecB upon binding to a model substrate-
      bovine pancreatic trypsin inhibitor (BPTI).
AB  - SecB is a homotetrameric cytosolic chaperone that forms part of the protein
      translocation machinery in E. coli. Due to SecB, nascent polypeptides are
      maintained in an unfolded translocation-competent state devoid of tertiary
      structure and thus are guided to the translocon. In vitro SecB rapidly binds to a
      variety of ligands in a non-native state. We have previously investigated the
      bound state conformation of the model substrate bovine pancreatic trypsin
      inhibitor (BPTI) as well as the conformation of SecB itself by using proximity
      relationships based on site-directed spin labeling and pyrene fluorescence
      methods. It was shown that SecB undergoes a conformational change during the
      process of substrate binding. Here, we generated SecB mutants containing but a
      single cysteine per subunit or an exposed highly reactive new cysteine after
      removal of the nearby intrinsic cysteines. Quantitative spin labeling was
      achieved with the methanethiosulfonate spin label (MTS) at positions C97 or E90C,
      respectively. Highfield (W-band) electron paramagnetic resonance (EPR)
      measurements revealed that with BPTI present the spin labels are exposed to a
      more polar/hydrophilic environment. Nanoscale distance measurements with double
      electron-electron resonance (DEER) were in excellent agreement with distances
      obtained by molecular modeling. Binding of BPTI also led to a slight change in
      distances between labels at C97 but not at E90C. While the shorter distance in
      the tetramer increased, the larger diagonal distance decreased. These findings
      can be explained by a widening of the tetrameric structure upon substrate binding
      much like the opening of two pairs of scissors.

PMID- 21848507
TI  - The Nicastrin ectodomain adopts a highly thermostable structure.
AB  - Nicastrin is a type I transmembrane glycoprotein, which is part of the high
      molecular weight gamma-secretase complex. gamma-Secretase is one of the key
      players associated with the generation of Alzheimer's disease pathology, since it
      liberates the neurotoxic amyloid beta-peptide. Four proteins Nicastrin, anterior
      pharynx-defective-1 (Aph-1), presenilin enhancer-2 (Pen-2) and Presenilin are
      essential to form the active gamma-secretase complex. Recently it has been shown,
      that Nicastrin has a key function in stabilizing the mature gamma-secretase
      complex and may also be involved in substrate recognition. So far no structural
      data for the Nicastrin ectodomain or any other gamma-secretase component are
      available. We therefore used Circular Dichroism (CD) spectroscopy to demonstrate
      that Nicastrin, similar to its homologues, the Streptomyces griseus
      aminopeptidase (SGAP) and the transferrin receptor (TfR), adopts a thermostable
      secondary structure. Furthermore, the Nicastrin ectodomain has an exceptionally
      high propensity to refold after thermal denaturation. These findings provide
      evidence to further support the hypothesis that Nicastrin may share evolutionary
      conserved properties with the aminopeptidase and the transferrin receptor family.

PMID- 21848508
TI  - Promising approaches in using magnetic nanoparticles in oncology.
AB  - The development of new and effective drug delivery systems for cancer treatment
      represents one of the significant challenges facing biomedical technology in the
      last decade. Among the different methods of drug delivery, magnetic drug
      targeting, by enabling specific delivery of chemotherapeutic agents through the
      use of magnetic nanoparticles and magnetic field gradient, could be a promising
      approach. Recently, magnetic nanoparticles have attracted additional attention
      because of their potential as contrast agents for magnetic resonance imaging and
      heat mediators for cancer therapy. This review summarizes these approaches in the
      use of magnetic nanoparticles in biomedical applications and novel methods for
      their optimization.

PMID- 21848509
TI  - Use of the Clark Twin Block functional appliance with and without an upper labial
      bow: a randomized controlled trial.
AB  - OBJECTIVES: To compare dentoalveolar and skeletal changes in two groups of Class
      II division 1 patients treated with different designs of Clark's Twin Block
      (CTB), with (Group 1) or without (Group 2) an upper labial bow. MATERIALS AND
      METHODS: A randomized controlled trial was conducted in the Department of
      Orthodontics at the East Kent Hospitals University NHS Foundation Trust, UK.
      Sixty-two white subjects (aged 10-14 years at the start of treatment, minimum
      overjet > 6 mm, molar relationship at least 1/2 unit Class II) were recruited.
      Subjects were divided into age- and sex-matched pairs, were randomly allocated to
      treatment with either appliance design, and were treated for 12 months, at which
      time additional data were collected. RESULTS: Sixty participants were available
      for final data collection. The two groups were well matched with respect to age
      (mean 12.5 years in Group 1; 12.3 years in Group 2). No statistical difference
      was noted between groups for any dentoalveolar or skeletal variables measured.
      Both groups experienced a reduction in overjet as a result of maxillary incisor
      retroclination, mandibular incisor proclination, and forward positioning of the
      pogonion. Maxillary molar distalization, mandibular molar mesialization, and ANB
      reduction also occurred in both groups. CONCLUSIONS: The addition of a maxillary
      labial bow to the CTB has no influence on dentoalveolar or skeletal changes, or
      on rate of overjet reduction, in relation to appliance therapy.

PMID- 21848512
TI  - Structural stabilization of protein 4.1R FERM domain upon binding to apo
      calmodulin: novel insights into the biological significance of the calcium
      independent binding of calmodulin to protein 4.1R.
AB  - In erythrocytes, 4.1R80 (80 kDa isoform of protein 4.1R) binds to the cytoplasmic
      tail of the transmembrane proteins band 3 and GPC (glycophorin C), and to the
      membrane-associated protein p55 through the N- (N-terminal), alpha- (alpha-helix
      rich) and C- (C-terminal) lobes of R30 [N-terminal 30 kDa FERM
      (4.1/ezrin/radixin/moesin) domain of protein 4.1R] respectively. We have shown
      previously that R30 binds to CaM (calmodulin) in a Ca2+-independent manner, the
      equilibrium dissociation constant (Kd) for R30-CaM binding being very similar (in
      the submicromolar range) in the presence or absence of Ca2+. In the present
      study, we investigated the consequences of CaM binding on R30's structural
      stability using resonant mirror detection and FTIR (Fourier-transform IR)
      spectroscopy. After a 30 min incubation above 40 degrees  C, R30 could no longer
      bind to band 3 or to GPC. In contrast, R30 binding to p55, which could be
      detected at a temperature as low as 34 degrees  C, was maintained up to 44
      degrees  C in the presence of apo-CaM. Dynamic light scattering measurements
      indicated that R30, either alone or complexed with apo-CaM, did not aggregate up
      to 40 degrees  C. FTIR spectroscopy revealed that the dramatic variations in the
      structure of the beta-sheet structure of R30 observed at various temperatures
      were minimized in the presence of apo-CaM. On the basis of Kd values calculated
      at various temperatures, DeltaCp and DeltaG degrees  for R30 binding to apo-CaM
      were determined as -10 kJ . K(-1) . mol-1 and ~ -38 kJ . mol(-1) at 37 degrees  C
      (310.15 K) respectively. These data support the notion that apo-CaM stabilizes
      R30 through interaction with its beta-strand-rich C-lobe and provide a novel
      function for CaM, i.e. structural stabilization of 4.1R80.

PMID- 21848510
TI  - Aptamers as therapeutics in cardiovascular diseases.
AB  - With many advantages over other therapeutic agents such as monoclonal antibodies,
      aptamers have recently emerged as a novel and powerful class of ligands with
      excellent potential for diagnostic and therapeutic applications. Typically
      generated through Systematic Evolution of Ligands by EXponential enrichment
      (SELEX), aptamers have been selected against a wide range of targets such as
      proteins, phospholipids, sugars, nucleic acids, as well as whole cells. DNA/RNA
      aptamers are single-stranded DNA/RNA oligonucleotides (with a molecular weight of
      5-40 kDa) that can fold into well-defined 3D structures and bind to their target
      molecules with high affinity and specificity. A number of strategies have been
      adopted to synthesize aptamers with enhanced in vitro/in vivo stability, aiming
      at potential therapeutic/diagnostic applications in the clinic. In cardiovascular
      diseases, aptamers can be developed into therapeutic agents as anti-thrombotics,
      anti-coagulants, among others. This review focuses on aptamers that were selected
      against various molecular targets involved in cardiovascular diseases: von
      Willebrand factor (vWF), thrombin, factor IX, phospholamban, P-selectin, platelet
      derived growth factor, integrin alpha(v)beta(3), CXCL10, vasopressin, among
      others. With continued effort in the development of aptamer-based therapeutics,
      aptamers will find their niches in cardiovascular diseases and significantly
      impact clinical patient management.

PMID- 21848513
TI  - Protein kinase D controls voluntary-running-induced skeletal muscle remodelling.
AB  - Skeletal muscle responds to exercise by activation of signalling pathways that co
      ordinate gene expression to sustain muscle performance. MEF2 (myocyte enhancer
      factor 2)-dependent transcriptional activation of MHC (myosin heavy chain) genes
      promotes the transformation from fast-twitch into slow-twitch fibres, with MEF2
      activity being tightly regulated by interaction with class IIa HDACs (histone
      deacetylases). PKD (protein kinase D) is known to directly phosphorylate skeletal
      muscle class IIa HDACs, mediating their nuclear export and thus derepression of
      MEF2. In the present study, we report the generation of transgenic mice with
      inducible conditional expression of a dominant-negative PKD1kd (kinase-dead PKD1)
      protein in skeletal muscle to assess the role of PKD in muscle function. In
      control mice, long-term voluntary running experiments resulted in a switch from
      type IIb+IId/x to type IIa plantaris muscle fibres as measured by indirect
      immunofluorescence of MHCs isoforms. In mice expressing PKD1kd, this fibre type
      switch was significantly impaired. These mice exhibited altered muscle fibre
      composition and decreased running performance compared with control mice. Our
      findings thus indicate that PKD activity is essential for exercise-induced MEF2
      dependent skeletal muscle remodelling in vivo.

PMID- 21848515
TI  - Ionotropic glutamate receptor (iGluR)-like channels mediate MAMP-induced calcium
      influx in Arabidopsis thaliana.
AB  - Binding of specific microbial epitopes [MAMPs (microbe-associated molecular
      patterns)] to PRRs (pattern recognition receptors) and subsequent receptor kinase
      activation are key steps in plant innate immunity. One of the earliest detectable
      events after MAMP perception is a rapid and transient rise in cytosolic Ca2+
      levels. In plants, knowledge about the signalling events leading to Ca2+ influx
      and on the molecular identity of the channels involved is scarce. We used a
      transgenic Arabidopsis thaliana line stably expressing the luminescent aequorin
      Ca2+ biosensor to monitor pharmacological interference with Ca2+ signatures
      following treatment with the bacterial peptide MAMPs flg22 and elf18, and the
      fungal carbohydrate MAMP chitin. Using a comprehensive set of compounds known to
      impede Ca2+-transport processes in plants and animals we found strong evidence
      for a prominent role of amino acid-controlled Ca2+ fluxes, probably through iGluR
      (ionotropic glutamate receptor)-like channels. Interference with amino acid
      mediated Ca2+ fluxes modulates MAMP-triggered MAPK (mitogen-activated protein
      kinase) activity and affects MAMP-induced accumulation of defence gene
      transcripts. We conclude that the initiation of innate immune responses upon
      flg22, elf18 and chitin recognition involves apoplastic Ca2+ influx via iGluR
      like channels.

PMID- 21848516
TI  - A novel allergen Tab y 1 with inhibitory activity of platelet aggregation from
      salivary glands of horseflies.
AB  - BACKGROUND: Horsefly sting causes allergic reactions in human body. However, our
      knowledge on horsefly allergens remains poor. OBJECTIVES: To identify the novel
      horsefly allergens and characterize their properties. METHODS: A native allergen
      protein Tab y 1 (apyrase) was purified from the salivary glands of the horsefly
      Tabanus yao Macquart by gel filtration and ion exchange chromatography. Its
      sequence was determined by Edman degradation and cDNA cloning. Its allergenicity
      was assessed by immunoblotting for specific IgE, basophil activation test, skin
      prick test (SPT), and competitive enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Tab y 1 showed a single diffusion band of 70 kDa on SDS-PAGE. Seventy
      percent (7/10) of patients with horsefly allergy tested positive to Tab y 1 in
      SPT; sera from 81% (30/37) of patients reacted to Tab y 1 on western blots.
      Purified Tab y 1 reduced approximately 42% sera IgE reactivity to horsefly
      salivary gland extract on a competitive ELISA. Tab y 1 upregulated the expression
      of CD63 and CCR3 on passively sensitized basophils by up to approximately 4.9
      fold. Tab y 1 also showed enzymatic activity to hydrolyze ATP and ADP, and potent
      antiplatelet aggregation and antithrombotic activities. CONCLUSION: The current
      work identified a novel major allergen of horsefly, Tab y 1, with antiplatelet
      aggregation and antithrombotic activities, which implicates Tab y 1 in helping
      horseflies suck host blood, meanwhile causing allergy in their human hosts.

PMID- 21848514
TI  - Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating
      sphingosine 1-phosphate.
AB  - S1P (sphingosine 1-phosphate) is a signalling molecule involved in a host of
      cellular and physiological functions, most notably cell survival and migration.
      S1P, which signals via a set of five G-protein-coupled receptors (S1P1-S1P5), is
      formed by the action of two SphKs (sphingosine kinases) from Sph (sphingosine).
      Interfering RNA strategies and SphK1 (sphingosine kinase type 1)-null (Sphk1-/-)
      mouse studies implicate SphK1 in multiple signalling cascades, yet there is a
      paucity of potent and selective SphK1 inhibitors necessary to evaluate the
      effects of rapid onset inhibition of this enzyme. We have identified a set of
      submicromolar amidine-based SphK1 inhibitors and report using a pair of these
      compounds to probe the cellular and physiological functions of SphK1. In so
      doing, we demonstrate that our inhibitors effectively lower S1P levels in cell
      based assays, but we have been unable to correlate SphK1 inhibition with changes
      in cell survival. However, SphK1 inhibition did diminish EGF (epidermal growth
      factor)-driven increases in S1P levels and Akt (also known as protein kinase
      B)/ERK (extracellular-signal-regulated kinase) phosphorylation. Finally,
      administration of the SphK1 inhibitor to wild-type, but not Sphk1-/-, mice
      resulted in a rapid decrease in blood S1P levels indicating that circulating S1P
      is rapidly turned over.

PMID- 21848517
TI  - T-cell and antibody responses to phospholipase A2 from different species show
      distinct cross-reactivity patterns.
AB  - BACKGROUND: Secreted phospholipases A2 (sPLA2) represent antigens to which humans
      may be rarely or frequently exposed. Thus, the investigation of humoral and
      cellular immune responses to sPLA2s from different species can provide a suitable
      model in the study of antibody and T-cell cross-reactivity. METHODS: Specific
      IgE, IgG1, IgG4, and IgA antibodies were analyzed by ELISA against sPLA2s from
      pancreas of Bos taurus (BT), Apis mellifera (AM) bee venom, Daboia russellii (DR)
      and Naja mossambica (NM) snake venoms, and human group III (hGIII) sPLA2 using
      sera of nonallergic beekeepers, AM-allergic patients, and healthy controls. T
      cell cross-reactivity was investigated in PBMC, and T-cell clones (TCC) are
      generated against AM sPLA2. RESULTS: Hyperimmune and allergic individuals showed
      high levels of sPLA2-specific IgG4 and significant IgG4 cross-reactivity between
      BT, DR, and NM sPLA2s. Furthermore, IgE, IgA, and IgG1 cross-reactivities against
      BT, DR, and NM sPLA2s were also detectable in the range of 22.2-44.8%. Allergic
      patients showed significant T-cell proliferative response to NM sPLA2 together
      with increased IFN-gamma and IL-13 production even though they had never been
      exposed to cobra venom. Although nonallergic healthy controls show no cross
      reactivity at T-cell level, they did have low levels of IgG4 and IgA against BT,
      DR, and NM sPLA2s. Human TCC spanning three major T-cell epitopes of AM sPLA2
      showed minor proliferative response to NM and hGIII sPLA2s. CONCLUSIONS: This
      study shows that T cells and antibodies may show cross-reactivity between
      different species without being naturally exposed to sPLA2s.

PMID- 21848518
TI  - Following a tick bite: double infections by tick-borne encephalitis virus and the
      spirochete Borrelia and other potential multiple infections.
AB  - In Central Europe and large parts of Asia, tick-borne-encephalitis (TBE) and Lyme
      borreliosis caused by the spirochetal bacterium of the genus Borrelia are among
      the most common diseases transmitted by the bite of a tick. When in regions with
      overlapping TBE virus and Borrelia endemicity, a tick bite causes the victim to
      become ill, it is important that appropriate serological and other laboratory
      investigations form part of the differential diagnosis. Account must always be
      taken of the fact that a tick bite may be followed by a double infection with the
      TBE virus and Borrelia. For this reason, a comprehensive diagnostic work-up aimed
      at detecting co-infection by both pathogens, even when the tick bite occurs in an
      endemic region for both pathogens but the initial clinical symptoms suggest an
      infection with only one of the two pathogens. The present article discusses a
      number of published cases of a co-infection with TBE virus and Borrelia and other
      potential multiple infections.

PMID- 21848519
TI  - Individualized toxicity-titrated 6-mercaptopurine increments during high-dose
      methotrexate consolidation treatment of lower risk childhood acute lymphoblastic
      leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot
      study.
AB  - This study explored the feasibility and toxicity of individualized toxicity
      titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment
      with High-dose methotrexate (HDM) (5000 mg/m(2), *3) in 38 patients with
      Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2) per day if
      they did not develop myelotoxicity within 2 weeks after HDM. 6MP could be
      increased in 31 patients (81%). Toxicity was acceptable and did not differ
      significantly between groups. Patients receiving 75 mg/m(2) per day had
      significantly shorter duration of treatment interruptions of 6MP than the
      remaining patients (P = 0.03). This study shows individualized toxicity-titrated
      6MP dosing during consolidation is feasible without increased risk of toxicity.

PMID- 21848520
TI  - Constitutional trisomy 8p11.21-q11.21 mosaicism: a germline alteration
      predisposing to myeloid leukaemia.
AB  - Juvenile myelomonocytic leukaemia (JMML) is a unique myeloproliferative disorder
      of early childhood. Frequently, mutations in NRAS, KRAS, PTPN11, NF1 or CBL are
      found in these patients. Monosomy 7 is the most common cytogenetic aberration. To
      identify submicroscopic genomic copy number alterations, 20 JMML samples were
      analysed by comparative genomic hybridization. Ten out of 20 samples displayed
      additional submicroscopic alterations. In two patients, an almost identical gain
      of chromosome 8 was identified. In both patients, fluorescence in situ
      hybridization confirmed a constitutional partial trisomy 8 mosaic (cT8M). A
      survey on 27 cT8M patients with neoplasms showed that 21 had myeloid
      malignancies, and five of these had a JMML. Notably, the region gained in our
      cases is the smallest gain of chromosome 8 reported in cT8M cases with
      malignancies so far. Our results dramatically reduce the critical region to
      8p11.21q11.21 harbouring 31 protein coding genes and two non-coding RNAs, e.g.
      MYST3, IKBKB, UBE2V2, GOLGA7, FNTA and MIR486--a finding with potential
      implications for the role of somatic trisomy 8 in myeloid malignancies. Further
      investigations are required to more comprehensively determine how constitutional
      partial trisomy 8 mosaicisms may contribute to leukaemogenesis in different
      mutational subtypes of JMML and other myeloid malignancies.

PMID- 21848521
TI  - Comment on Guidelines on oral anticoagulation with warfarin--4th edition.

PMID- 21848523
TI  - A novel t(1;8)(q25;p11.2) translocation associated with 8p11 myeloproliferative
      syndrome.

PMID- 21848522
TI  - Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor
      (G-CSF) priming for relapsed and refractory acute myeloid leukaemia.
AB  - This phase I/II study was conducted to determine the maximum tolerated dose,
      toxicity, and efficacy of clofarabine in combination with high dose cytarabine
      and granulocyte colony-stimulating factor (G-CSF) priming (GCLAC), in the
      treatment of patients with relapsed or refractory acute myeloid leukaemia (AML).
      Dose escalation of clofarabine occurred without dose-limiting toxicity, so most
      patients were treated at the maximum dose, 25 mg/m(2) per day with cytarabine 2
      g/m(2) per day, each for 5 d, and G-CSF 5 MUg/kg, beginning the day before
      chemotherapy and continuing daily until neutrophil recovery. The complete
      remission (CR) rate among the 46 evaluable patients was 46% (95% confidence
      interval [CI] 31-61%) and the CR + CR but with a platelet count <100 * 10(9)/l
      rate was 61% (95% CI 45-75%). Multivariate analysis showed that responses to
      GCLAC were independent of age, cytogenetic risk category, and number of prior
      salvage regimens. GCLAC is highly active in relapsed and refractory AML and
      warrants prospective comparison to other regimens, as well as study in untreated
      patients.

PMID- 21848524
TI  - Combination therapy with ofatumumab and bendamustine in xenograft model of
      chronic lymphocytic leukaemia.

PMID- 21848525
TI  - Primer design and transcript quantification of a highly multiplexed RT-PCR for a
      nonmodel avian species.
AB  - Multiplexed qRT-PCR assays are currently lacking for nearly all species without
      genome or transcriptome resources. Here, we present a strategy for primer design
      of highly multiplexed qRT-PCR assays, evaluate Beckman Coulter's Quant Tool gene
      expression quantification software and provide details of our assay for the North
      American songbird Carpodacus mexicanus (house finch), for which only small
      sections of genome sequence are available. We combined Beckman Coulter's eXpress
      Designer module for creating custom multiplex primers with the free, online
      program Amplify 3 to design and evaluate primers computationally before testing
      them empirically. We also generated a standard curve for each gene included in
      the final multiplex. We compared models using cubic and quadratic polynomial
      estimators that did and did not force the intercept through zero. Ultimately, we
      used the sequences available for 316 clones differentially expressed in cDNA
      macroarray and microarray comparisons, and from these sequences, we were able to
      generate a set of transcript-specific primers for use with the GeXP analyser for
      20 house finch genes.

PMID- 21848526
TI  - Effect of experimental jaw-muscle pain on the spatial distribution of surface EMG
      activity of the human masseter muscle during tooth clenching.
AB  - This study tested the hypothesis that painful injections of glutamate into the
      human masseter muscle differentially affect the distribution of the
      electromyographic (EMG) activity in the masseter muscle at rest and during tooth
      clenching. Surface EMG signals were recorded bilaterally from the superficial
      masseter of nine healthy men with a grid of 32 electrodes, before and after
      intramuscular injection of glutamate or isotonic saline, during rest and
      isometric contractions at 20%, 40%, 60% and 80% of the maximal voluntary bite
      force. Intramuscular injection of glutamate evoked moderate pain (0-10 visual
      analogue scale: 6.4 +/- 1.4), with sensory-discriminative characteristics of the
      perceived pain, evaluated with the use of the McGill Pain Questionnaire (MPQ),
      similar to those previously reported for patients with temporomandibular
      disorders. There was no effect of the glutamate injection on EMG amplitude during
      rest, whereas during tooth clenching, the spatial distribution of the masseter
      EMG activity on both sides was more uniform in the painful condition compared to
      the control condition. Moreover, the overall EMG amplitude decreased on both
      sides during the more forceful tooth clenching following glutamate injection. In
      conclusion, a unilateral painful stimulation was associated with a bilateral
      inhibition of the masseter muscles during tooth clenching which resulted in a
      more uniform distribution of EMG activity.

PMID- 21848527
TI  - Classifying orofacial pains: a new proposal of taxonomy based on ontology.
AB  - We propose a new taxonomy model based on ontological principles for disorders
      that manifest themselves through the symptom of persistent orofacial pain and are
      commonly seen in clinical practice and difficult to manage. Consensus meeting of
      eight experts from various geographic areas representing different perspectives
      (orofacial pain, headache, oral medicine and ontology) as an initial step towards
      improving the taxonomy. Ontological principles were introduced, reviewed and
      applied during the consensus building process. Diagnostic criteria for persistent
      dento-alveolar pain disorder (PDAP) were formulated as an example to be used to
      model the taxonomical structure of all orofacial pain conditions. These criteria
      have the advantage of being (i) anatomically defined, (ii) in accordance with
      other classification systems for the provision of clinical care, (iii)
      descriptive and succinct, (iv) easy to adapt for applications in varying
      settings, (v) scalable and (vi) transferable for the description of pain
      disorders in other orofacial regions of interest. Limitations are that the
      criteria introduce new terminology, do not have widespread acceptance and have
      yet to be tested. These results were presented to the greater conference
      membership and were unanimously accepted. Consensus for the diagnostic criteria
      of PDAP was established within this working group. This is an initial first step
      towards developing a coherent taxonomy for orofacial pain disorders, which is
      needed to improve clinical research and care.

PMID- 21848528
TI  - La Crosse encephalitis surveillance using single versus paired serologic testing.
AB  - We evaluated the validity of single versus paired serologic testing for La Crosse
      virus (LACV) encephalitis surveillance. Compared with paired serology, a single
      positive IgG or IgM immunoflourescent antibody titre appears useful for LACV
      encephalitis surveillance with sensitivity, 75%; specificity, 98%; positive
      predictive value, 95%; and overall test efficiency 92%.

PMID- 21848529
TI  - Combination of tissue expansion and porcine mesh for secondary abdominal wall
      closure after pediatric liver transplantation.
AB  - We report the case of a two and a half yr boy hospitalized in our Pediatric
      Transplantation Unit for portal vein thrombosis following liver transplantation.
      After performing a meso-Rex shunt, abdominal wall closure was impossible without
      compressing the portal flow. A combination of two techniques was used to perform
      the reconstruction of the muscular fasciae and skin layers. The association of
      tissue expanders and porcine mesh (Surgisis((r))) allowed complete abdominal wall
      closure with good functional and esthetic results. Use of both techniques is a
      useful alternative for difficult abdominal closure after liver pediatric
      transplantation.

PMID- 21848530
TI  - Use of a radiofrequency probe for tenoscopic-guided annular ligament desmotomy.
AB  - REASONS FOR PERFORMING STUDY: Annular ligament desmotomy is commonly performed in
      horses with chronic tenosynovitis. Previously reported tenoscopic techniques have
      limitations related to haemorrhage and awkward instrumentation. Radiofrequency
      (RF) energy affords precision and excellent haemostasis and may be a good
      alternative to sharp transection of the annular ligament in horses. OBJECTIVE: To
      describe a technique for using a RF probe for tenoscopic-guided annular ligament
      desmotomy and to report the clinical outcome of horses in which it was performed.
      METHODS: Cadaver specimens (n = 14) and live horses undergoing unrelated terminal
      procedures (n = 2) were used to optimise the tenoscopic-guided RF annular
      ligament desmotomy technique. Records were examined for all horses undergoing
      annular ligament desmotomy with an RF probe from 2003 to 2008 for which follow-up
      of >1 year post operatively was available. RESULTS: The annular ligament was
      successfully transected in the cadaver and live horse model limbs using 2
      different commercially available RF probes. Complete transection was achieved
      with practice and confirmed on gross dissection. Histopathology did not reveal
      any collateral damage to surrounding tissue. Follow-up of >1 year was available
      for 6 of 7 clinical cases. Four of 6 horses returned to work. Owners were
      satisfied with the outcome in all cases. CONCLUSIONS: Desmotomy using a RF probe
      allows precise tissue transection under tenoscopic guidance without damage to
      surrounding structures or haemorrhage. With experience, it is an easily performed
      technique. In clinical patients, an acceptable outcome may be expected. POTENTIAL
      RELEVANCE: Tenoscopic-guided RF annular ligament desmotomy offers advantages,
      including reliable haemostasis and precise tissue transection, over previously
      reported techniques and is a viable surgical alternative for treating horses with
      annular ligament desmitis and other complex pathology within the tendon sheath.

PMID- 21848531
TI  - Circannual variation in plasma adrenocorticotropic hormone concentrations in the
      UK in normal horses and ponies, and those with pituitary pars intermedia
      dysfunction.
AB  - REASONS FOR PERFORMING STUDY: Pituitary pars intermedia dysfunction (PPID) is a
      common endocrinopathy, frequently diagnosed via plasma adrenocorticotropic
      hormone (ACTH) concentrations. Seasonal variation in plasma ACTH concentrations
      has been described in normal horses prompting caution in diagnosing PPID at
      certain times of the year. The aims of this study were to determine appropriate
      reference intervals for equine plasma ACTH throughout the year; and to examine
      the circannual variation of plasma ACTH concentrations in PPID cases. HYPOTHESIS:
      Plasma ACTH can be used as a test for PPID throughout the year with the use of
      appropriate reference intervals. METHODS: Data for reference interval
      calculations were obtained from samples collected from inpatients of Liphook
      Equine Hospital (non-PPID group, n=156). Data from PPID cases (n=941) were
      obtained from samples submitted to the Liphook Equine Hospital Laboratory from
      horses with a clinical suspicion of PPID found to have plasma ACTH concentrations
      greater than our upper reference interval for that time of year. RESULTS: Upper
      limits for reference interval of plasma ACTH were 29 pg/ml between November and
      July and 47 pg/ml between August and October. Circannual variation in plasma ACTH
      occurred in both non-PPID and PPID horses with the highest ACTH concentrations
      found between August and October in both groups (P<0.0001). The greatest
      difference between the 2 populations also occurred between August and October.
      CONCLUSIONS: Plasma ACTH can be used for the diagnosis and monitoring of PPID
      throughout the year with the use of appropriate reference intervals. These
      findings demonstrate an increase in pituitary gland secretory activity during the
      late summer and autumn in both normal and PPID cases.

PMID- 21848532
TI  - Endoscopic evaluation of the navicular bursa: observations, treatment and outcome
      in 92 cases with identified pathology.
AB  - REASONS FOR PERFORMING STUDY: Diagnostic navicular bursoscopy has been described
      in limited cases. Review of greater numbers is needed to define its contribution
      to case management and prognostic values. OBJECTIVES: To report: 1) clinical,
      diagnostic and endoscopic findings in a series of cases, 2) surgical techniques
      and case outcomes and 3) prognostic values. The authors hypothesise: 1) lameness
      localising to the navicular bursa is commonly associated with dorsal border deep
      digital flexor tendon (DDFT) lesions, 2) endoscopy allows extent of injuries to
      be assessed and treated, 3) case outcome relates to severity of DDFT injury and
      4) the technique is safe and associated with little morbidity. MATERIALS AND
      METHODS: All horses that underwent endoscopy of a forelimb navicular bursa for
      investigation of lameness were identified. Case files were reviewed and those
      with injuries within the bursa selected for further analysis. RESULTS: One
      hundred-and-fourteen horses were identified. Ninety-two had injuries within the
      bursa and DDFT injuries were identified in 98% of bursae. Of those examined with
      magnetic resonance imaging (MRI), 56% had combination injuries involving the DDFT
      and navicular bone. Sixty-one percent of horses returned to work sound, 42%
      returned to previous performance. Horses with extensive tearing and combination
      injuries of the DDFT and navicular bone identified with MRI, had worse outcomes.
      CONCLUSIONS: Lameness localising to the navicular bursa is commonly associated
      with injuries to the dorsal border of the DDFT. Endoscopy permits identification
      and characterisation of injuries within the navicular bursa and enables lesion
      management. Outcome following debridement is related to severity of injury but
      overall is reasonable. POTENTIAL RELEVANCE: Horses with lameness localising to
      the navicular bursa may have tears of the DDFT. Bursoscopy is able to contribute
      diagnostic and prognostic information and debridement of lesions improves outcome
      compared to cases managed conservatively.

PMID- 21848533
TI  - Cross-sectional survey of owner knowledge and husbandry practices, tack and
      health issues affecting working horses in Lesotho.
AB  - REASONS FOR PERFORMING STUDY: To establish baseline parameters of equine health,
      owner knowledge and husbandry practices and tack against which benefits to local
      horses arising from an equine charity's training programme in Lesotho could be
      measured. OBJECTIVES: To describe and investigate associations between owner
      knowledge and equine husbandry practices, horse health and tack-related
      parameters prior to the start of the training programme. METHODS: A cross
      sectional survey was undertaken in the catchment area of students attending the
      first training course. Owners from randomly selected villages were interviewed
      about horse care using a standardised, structured questionnaire, administered
      face to face in local language. Horses were clinically examined and tack assessed
      according to standardised protocols. RESULTS: Clinical examinations were
      performed on 312 horses and 287 owners were interviewed. Owners had variable
      knowledge of equine husbandry and limited understanding of appropriate primary
      and preventive healthcare. Equine health problems identified included ecto- and
      endoparasite infestation, mouth lesions, overgrown and unbalanced feet and tack
      associated wounds. The majority of tack was in poor condition, dirty and ill
      fitting. With the exception of below-average body condition score, no
      associations were found between key adverse horse-related clinical findings and
      owners reporting their horse as being 'unhealthy'. CONCLUSIONS: Working horses in
      Lesotho have a range of physical problems, many of which could be ameliorated
      through targeted owner education. With limited access to veterinary advice and
      scarce resources, improved availability of affordable local equine trade skills
      is key to improving equine health. POTENTIAL RELEVANCE: Findings could be used to
      inform and direct training programmes to maximise benefits to equine health and
      to serve as a baseline against which to monitor effects of educational and other
      interventions.

PMID- 21848534
TI  - Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 1:
      Prevalence of antimicrobial-resistant Escherichia coli and methicillin-resistant
      Staphylococcus aureus.
AB  - REASONS FOR PERFORMING STUDY: The increasing prevalence of antimicrobial
      resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and
      antimicrobial-resistant Escherichia coli represents a significant problem.
      However, the carriage of such bacteria by horses in the UK has not been well
      characterised. OBJECTIVES: To estimate the prevalence of nasal carriage of MRSA
      and faecal carriage of antimicrobial-resistant E. coli amongst horses in the
      general equine community of the mainland UK. METHODS: A cross-sectional study of
      horses recruited by 65 randomly selected equine veterinary practices was
      conducted, with nasal swabs and faecal samples collected. Faecal samples were
      cultured for antimicrobial-resistant E. coli. Nasal swabs were cultured for
      staphylococcal species; methicillin-resistant isolates identified as S. aureus
      were characterised by SCCmec and spa gene typing. Multilevel logistic regression
      models were used to calculate prevalence estimates with adjustment for clustering
      at practice and premises levels. Spatial variation in risk of antimicrobial
      resistance was also examined. RESULTS: In total, 650 faecal samples and 678 nasal
      swabs were collected from 692 horses located on 525 premises. The prevalence of
      faecal carriage of E. coli with resistance to any antimicrobial was 69.5% (95% CI
      65.9-73.1%) and the prevalence of extended-spectrum beta-lactamase (ESBL)
      producing E. coli was 6.3% (95% CI 4.1-9.6%). The prevalence of nasal carriage of
      MRSA was 0.6% (95% CI 0.2-1.5%). Spatial analysis indicated variation across the
      UK for risk of carriage of resistant and multidrug-resistant (resistant to more
      than 3 antimicrobial classes) E. coli. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Carriage of MRSA by horses in the community appears rare, but the prevalence of
      antimicrobial-resistant E. coli (including ESBL-producing E. coli) is higher. A
      high prevalence of antimicrobial-resistant bacteria could have significant health
      implications for the horse population of the UK.

PMID- 21848535
TI  - Clinical, radiological and ultrasonographic features, treatment and outcome in 22
      horses with caudal distal radial osteochondromata.
AB  - REASONS FOR PERFORMING STUDY: Although a well recognised clinical entity, only
      small numbers of osteochondromata on the caudal distal radius have previously
      been published and its occurrence in young racing Thoroughbreds has not
      previously been reported. Identification and management of associated lesions in
      the deep digital flexor tendon have received scant attention in the literature.
      HYPOTHESIS: Osteochondromata of the caudal distal radius occur commonly in young
      racing Thoroughbreds. They vary in size and location, sagittally and
      proximodistally, but the majority cause impingement damage to the deep digital
      flexor tendon. METHODS: Case records and diagnostic images of horses with
      osteochondromata of the caudal distal radius were reviewed retrospectively and
      follow-up information obtained. RESULTS: Twenty-five osteochondromata were
      identified in 22 horses, 19 of which were Thoroughbreds. All osteochondromata
      were metaphyseal. Twenty-two were in the middle one-third of the bone and
      laceration of the adjacent deep digital flexor tendon was identified in 21 limbs.
      Treatment in all cases consisted of removal of the osteochondroma with
      debridement of the deep digital flexor tendon when this was affected. All horses
      returned to work and none exhibited any evidence of recurrence. CONCLUSION:
      Osteochondromata of the caudal distal radius occur in young racing Thoroughbreds
      but are also identified in other horses. They have a consistent metaphyseal
      location and most are found in the middle one-third of the radius. Size varies,
      but most cause laceration of the adjacent deep digital flexor tendon. Treatment
      by removal of the mass and debridement of the tendon is associated with a good
      prognosis. POTENTIAL RELEVANCE: Osteochondromata of the caudal distal radius are
      an important cause of tenosynovitis of the carpal sheath of the digital flexor
      tendons in young racing Thoroughbreds. When present in the most common location
      of the middle one-third of the bone, they are likely to cause impingement damage
      to the deep digital flexor tendon. Tenoscopic surgery offers a good prognosis.

PMID- 21848536
TI  - Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 2: Risk
      factors for faecal carriage of antimicrobial-resistant Escherichia coli in
      horses.
AB  - REASONS FOR PERFORMING STUDY: The increasing prevalence of antimicrobial
      resistant bacteria such as antimicrobial-resistant and extended spectrum beta
      lactamase (ESBL)-producing Escherichia coli represents a significant problem for
      human and veterinary medicine. Despite this, the risk factors for faecal carriage
      of such bacteria by horses in the UK, particularly those in the wider community,
      have not been well described. OBJECTIVES: To characterise the risk factors for
      faecal carriage of antimicrobial-resistant E. coli amongst horses in the mainland
      UK. METHODS: A cross-sectional study of horses recruited by 65 randomly selected
      equine veterinary practices was conducted, with a faecal sample collected and
      self-administered questionnaire completed by the horse owner. Faecal samples were
      cultured for antimicrobial-resistant E. coli, with isolates confirmed as E. coli
      having their antimicrobial resistance profile determined. Multilevel,
      multivariable logistic regression models were used to investigate risk factors
      for the carriage of antimicrobial-resistant E. coli in the sample population.
      RESULTS: Faecal samples and completed questionnaires were obtained for 627 horses
      located on 475 premises. Recent hospitalisation, contact with specific types of
      nonequid animals, the type of premises, the surrounding land use, the reason for
      veterinary treatment received in the last 6 months and antimicrobial treatment in
      the previous 10 days were identified as risk factors for many of the
      antimicrobial-resistance outcomes considered. Being stabled on the same yard as a
      recently hospitalised horse was identified as a risk factor for increased risk of
      carriage of ESBL-producing E. coli. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Increasing antimicrobial resistance may have significant health implications for
      the horse population of Great Britain. This form of epidemiological investigation
      highlights potential risk factors that may be controlled to limit the extent of
      the problem.

PMID- 21848537
TI  - Injuries of the calcaneal insertions of the superficial digital flexor tendon in
      19 horses.
AB  - REASONS FOR PERFORMING STUDY: Injuries of the calcaneal insertions of the
      superficial digital flexor tendon and their relationship to displacement of the
      tendon from the calcaneus have not previously been reported. OBJECTIVES: To
      describe findings made on clinical cases with disruption of the calcaneal
      insertions of the superficial digital flexor tendon (SDFT) including observations
      on their role in horses with unstable subluxation of the tendon. To describe
      novel surgical techniques and the results of treatment. HYPOTHESES: Disruption of
      the calcaneal insertions of the SDFT is associated with lameness and distension
      of the calcaneal bursa. Unstable displacement of the SDFT from the calcaneus is a
      more complex injury than incomplete disruption of one of its calcaneal
      insertions. METHODS: The case records and diagnostic images of horses with
      lesions involving the calcaneal insertions of the SDFT, which were confirmed by
      endoscopic evaluation of calcaneal bursa between 2005 and 2009, were reviewed.
      RESULTS: Nineteen horses were identified including 7 that had unstable
      displacement of the tendon from the calcaneus. Following endoscopic surgery, 9 of
      12 horses with stable tendons and 6 of 7 horses with unstable displaced SDFTs
      returned to work. CONCLUSION: Tearing of the calcaneal insertions of the SDFT is
      associated with lameness and distension of the calcaneal bursa; endoscopic
      removal of the torn tissue carries a good prognosis. Horses with unstable
      displacement of the tendon have also disruption of the tendon fibrocartilage cap.
      Removal of this results in stable subluxation and can return horses to athletic
      activity. Both lesions can be detected by preoperative ultrasonography. POTENTIAL
      RELEVANCE: Tearing of the calcaneal insertions of the SDFT should be included in
      the differential diagnoses of lame horses with distended calcaneal bursae.
      Tearing of the tendon fibrocartilage cap in horses with unstable displacement of
      the SDFT is a plausible explanation of the clinical features of the injury and
      explains previously unreliable results of reconstructive surgeries. Subtotal
      resection is a technically demanding technique but appears to offer an improved
      prognosis.

PMID- 21848538
TI  - Gal/non-Gal antigens in pig tissues and human non-Gal antibodies in the GalT-KO
      era.
AB  - Our knowledge regarding Gal and non-Gal antigens in GalT-KO pig tissues can be
      summarized as alpha3Galactosyl-tranferase gene knock out eliminates the
      Galalpha3Galbeta4GlcNAc-R antigen expression in pig tissues as well as anti-Gal
      antibody binding. Other Galalpha-terminating saccharides (e.g. iGb3 glycolipids
      and Galalpha2 determinants) may be present but have not been documented.
      alpha3Galactosyl-tranferase gene knock out slightly changes the carbohydrate
      antigen expression but no "new" antigens recognized by the human immune system
      have been found. Non-Gal antigens are both of protein and carbohydrate nature but
      their exact chemical structures are poorly defined. Regarding human non-Gal
      antibodies our knowledge is as Non-Gal antibodies exist naturally and increase in
      humans/non-human primate (NHP) receiving WT or GalT-KO pig grafts. Non-Gal
      antibodies with new antigen epitope recognition can be induced in humans/NHP
      after challenge by WT or GalT-KO pig grafts. Non-Gal antibodies react with both
      carbohydrates and proteins. Part of the protein reactivity is directed to
      glycoprotein carbohydrates chains. Non-Gal antibodies reacting with neuraminic
      acid terminated saccharides (both N-Acetyl and N-Glycoloyl variants) are present
      in humans/NHP. Anti-neuraminic acid antibodies are increased, as well as induced,
      after grafting pig organs into humans/NHP. Non-Gal antibodies does not cause
      hyperacute xenorejection but can be cytotoxic and cause xenoorgan damage. If
      humans sensitized to HLA antigens are at a higher risk of rejecting pig xenograft
      compared with non-sensitized individuals is not fully clarified. Clinical trials
      are needed to evaluate the relevance of non-Gal antigens/antibodies and for the
      xenofield to advance.

PMID- 21848539
TI  - A record of international meetings on xenotransplantation 1988-2010.

PMID- 21848540
TI  - Microcirculatory alterations after orthotopic pig-to-baboon heart
      transplantation.
AB  - BACKGROUND: Whilst macrohemodynamic function of porcine xenografts transplanted
      into baboons has been assessed perioperatively, the ability of the xenograft to
      maintain systemic microcirculatory perfusion has not been investigated after pig
      to-baboon xenotransplantation so far. METHODS: We investigated the sublingual
      microcirculation of six baboons undergoing orthotopic transplantation of hCD46
      transgenic pig hearts using orthogonal polarization spectral imaging.
      Microvascular measurements were performed after induction of anesthesia, in the
      early phase of cardiopulmonary bypass (CPB), during reperfusion of the porcine
      heart and 1 h after the xenograft had resumed its life-supporting function.
      Microvascular blood flow was analyzed semiquantitatively and the number of
      visualized cell-to-cell interactions was counted. RESULTS: The proportion of
      continuously perfused microvessels was 97 (96 to 97) % at baseline and 95 (94 to
      97) % in the early phase of CPB. It decreased significantly (P < 0.05) during CPB
      to 89 (84 to 91), and alterations were still present (P < 0.05) when CPB was
      terminated and the xenograft had taken over systemic perfusion 83 (81 to 85) %.
      The microcirculatory changes correlated with the lactate levels (y = 18.1-0.18 x;
      r(2) = 0.55; P < 0.001), but no correlation with macrohemodynamic parameters was
      found. CONCLUSION: Microvascular blood flow is altered after orthotopic pig-to
      baboon heart transplantation, despite systemic hemodynamic parameters being well
      maintained by the porcine xenograft. These changes are moderate but persist after
      termination of CPB. Further studies need to elucidate whether these changes are
      transient or add to the mortality associated with cardiac xenotransplantation.

PMID- 21848541
TI  - Paramagnetic microparticles do not elicit islet cytotoxicity with co-culture or
      host immune reactivity after implantation.
AB  - BACKGROUND: Paramagnetic microparticles (MPs) may be useful in pancreatic islet
      purification, in particular purification of porcine islets as a potential
      xenotransplantation product. We assessed whether MPs affect islet function or
      induce an adverse effect following implantation. METHODS: Porcine islets were co
      cultured with 0, 500, and 1500 MPs per islet equivalent (IE) for 1 day and with 0
      and 1500 MPs/IE for 7 days. Fractional viability was assessed using oxygen
      consumption rate normalized to DNA content (OCR/DNA) and after 7-day co-culture
      by perifusion glucose-stimulated insulin secretion (GSIS) and by transplantation
      under the renal capsule of diabetic nude mice. To assess an inflammatory response
      or immune reaction, MPs (~10(7)) were implanted under the renal capsule of
      C57BL/6 mice. RESULTS: No statistically significant differences were measured in
      OCR/DNA (mean +/- SE) following 1-day co-culture with 0, 500, or 1500 MPs/IE
      (243.3 +/- 4.5, 211.3 +/- 8.1, or 230.6 +/- 11.3 nmol/min.mgDNA, respectively) or
      following 7-day co-culture with 0 or 1500 MPs/IE (248.5 +/- 1.4 or 252.9 +/- 4.7
      nmol/min.mgDNA, respectively). GSIS was not affected by the presence of MPs;
      first- and second-phase insulin area-under-the-curve (mean +/- SE) reflected no
      statistically significant differences after 7-day co-culture between 0 and 1500
      MPs/IE (8.36 +/- 0.29 and 8.45 +/- 0.70 pg/ml.min.ngDNA for first-phase; 69.73 +/
      2.18 and 65.70 +/- 4.34 pg/ml.min.ngDNA for second-phase, respectively). Islets
      co-cultured with MPs normalized hyperglycemia in diabetic nude mice, suggesting
      no adverse effects on in vivo islet function. Implantation of MPs did not elicit
      tissue injury, inflammatory change or immune reactivity. CONCLUSION: MPs do not
      adversely affect islet viability or function during co-culture, and MPs are not
      immune reactive following implantation.

PMID- 21848542
TI  - ASGR1 expressed by porcine enriched liver sinusoidal endothelial cells mediates
      human platelet phagocytosis in vitro.
AB  - BACKGROUND: Porcine liver xenografts represent a potential solution to the organ
      shortage, but thrombocytopenia occurs within minutes to hours after
      xenotransplantation, preventing clinical application. Recently, it was discovered
      that porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human
      platelets. We examined the role of ASGR1 in binding and removing human platelets
      by the pig liver endothelium. METHODS: Primary porcine enriched LSEC (eLSEC) were
      characterized by flow cytometry, immunoblot, quantitative PCR, and
      immunohistochemistry using confocal microscopy. Phagocytosis inhibition assays
      using anti-ASGR1 and an ASGR1 substrate were performed. ASGR1 was targeted for
      siRNA knockdown, and ASGR1-reduced cells were tested for human platelet binding
      and phagocytosis. RESULTS: ASGR1 is expressed by eLSEC. Human platelet binding
      and phagocytosis by porcine eLSEC was inhibited by asialofetuin, but not fetuin,
      suggesting an interaction with galactose beta1-4 N-acetyl glucosamine. Anti-ASGR1
      antibodies inhibited human platelet binding in a dose-dependent manner. Knockdown
      experiments using siRNA reduced ASGR1 expression in asynchronous primary eLSEC by
      40%-80%. There was a 20% reduction in translated protein significantly correlated
      with a 21% decrease in human platelet binding. CONCLUSIONS: ASGR1 on porcine
      eLSEC mediates phagocytosis of xenogeneic platelets.

PMID- 21848543
TI  - Xenoreactive CD4+ memory T cells resist inhibition by anti-CD44 mAb and reject
      islet grafts via a Th2-dependent pathway.
AB  - BACKGROUND: Memory T cells are a significant barrier to the induction of
      transplant tolerance. Our previous study demonstrated that multiple applications
      of anti-CD44 monoclonal antibody (mAb) could significantly inhibit CD4(+) memory
      T cells from mediating rejection of cardiac allografts. Now, we sought to explore
      the effect and mechanism of anti-CD44 mAb on the rejection of islet allografts
      and xenografts mediated by CD4(+) memory T cells. METHODS: In this study, we
      first engrafted skin grafts of C57BL/6 (B6) mice or Dark Agouti (DA) rats onto
      BALB/c mice to induce donor-reactive memory T cells. We adoptively transferred
      purified CD4(+) memory T cells to BALB/c origin nude mice and then transplanted
      islet allografts and xenografts to produce the Allo-Tx and Xeno-Tx models,
      respectively. We subsequently administered multiple anti-CD44 mAb and observed
      changes in the survival times of the islet grafts. RESULTS: In the Allo-Tx model,
      the mean survival time (MST) of the grafts was 7.7 days in the isotype group, and
      20.3 days in the anti-CD44 group. In the Xeno-Tx model, the MST of the grafts was
      7.2 days in the isotype group and 8.2 days in the anti-CD44 group. Compared with
      the isotype group, CD4(+) T cells on the grafts in the anti-CD44 group were
      significantly decreased in both the Allo-Tx and Xeno-Tx models, but the
      proportion of CD4(+) memory T cells in the spleens and draining lymph nodes of
      the recipient nude mice in the anti-CD44 group was significantly decreased in the
      Allo-Tx model, while it was increased in the Xeno-Tx model. The production of
      donor-specific IgG antibody in the anti-CD44 group did not vary in the Allo-Tx
      model, while it was markedly elevated in the Xeno-Tx model. Furthermore, the
      expression of interferon gamma in the anti-CD44 group was markedly decreased in
      both the Allo-Tx and Xeno-Tx models, while the expression of IL-4 in the anti
      CD44 group was significantly increased only in the Xeno-Tx model. CONCLUSION:
      Multiple applications of the anti-CD44 mAb could significantly inhibit donor
      reactive CD4(+) memory T cells from rejecting grafts via a Th1-dependent pathway,
      but xenoreactive CD4(+) memory T cells can avoid the effects of anti-CD44 mAb to
      reject islet xenografts via a Th2-dependent pathway.

PMID- 21848544
TI  - Xenotransplantation literature update, May-June 2011.

PMID- 21848545
TI  - Effect of treatment with fixed and removable dental prostheses. An oral health
      related quality of life study.
AB  - The aim of the study was to evaluate patient-reported effects of treatment with
      fixed dental prostheses (FDP) and removable dental prostheses (RDP) and relate
      the change in Oral Health Related Quality of Life (OHRQoL) to the type of
      treatment and objective dental variables of aesthetics and mastication.
      Additionally, the purpose of the study was to identify aspects of impairment and
      improvement that the treatments caused. Fixed dental prostheses treatment was
      performed in 200 patients and RDP treatment in 107 patients. Gender, age, region
      of replacement, and number of teeth present and replaced were obtained. The
      participants completed the Oral Health Impact Profile 49 (OHIP-49) before and
      after treatment. A control group with no need for dental treatment also completed
      the OHIP-49. All participants had a significant improvement in OHRQoL. The
      improvement was higher for the RDP group than the FDP group. Removable dental
      prostheses that replaced only masticatory teeth did not improve the OHRQoL
      significantly. The improvement in OHRQoL for both the FDP and RDP groups was not
      at the level of the control group. Higher age was associated with lower
      improvement in OHRQoL. Higher age, being a woman and having teeth replaced in the
      aesthetic zone were associated with deterioration in OHRQoL. Both RDP treatment
      and FDP treatment were associated with a reduction in the problems most
      frequently reported before treatment. Treatment with RDP was associated with new
      problems caused by the RDP. Fixed dental prostheses and RDP treatments improved
      OHRQoL and reduced the number of problems. The RDP participants improved more
      than the FDP participants.

PMID- 21848549
TI  - A material advance in evaluating patients with a facial palsy: the Glasgow Facial
      Palsy System.

PMID- 21848550
TI  - Surgical technique for excision of first branchial cleft anomalies: how we do it.

PMID- 21848551
TI  - Intra-auricular modification of facelift incision with sternocleidomastoid flap-
      a cosmetic approach for parotidectomy: how we do it.

PMID- 21848552
TI  - Differentiated thyroid carcinoma with distant metastases at diagnosis: how we do
      it.

PMID- 21848553
TI  - The natural history of untreated squamous cell carcinoma of the head and neck:
      how we do it.

PMID- 21848554
TI  - Speech therapy in the treatment of globus pharyngeus: how we do it.

PMID- 21848555
TI  - Re: Appraisal of litigation against English Health Trusts in the treatment of
      adults with ENT pathology.

PMID- 21848558
TI  - Re: Comparison of therapeutic results in sudden sensorineural hearing loss
      with/without additional hyperbaric oxygen therapy: a retrospective review of 465
      audiologically controlled cases.

PMID- 21848560
TI  - Re: Comparison of therapeutic results in sudden sensorineural hearing loss
      with/without additional hyperbaric oxygen therapy: a retrospective review of 465
      audiologically controlled cases.

PMID- 21848562
TI  - Re: A randomised controlled trial comparing spontaneous healing, gelfoam
      patching, and edge-approximation plus gelfoam patching in traumatic tympanic
      membrane perforation with in-/everted edges.

PMID- 21848564
TI  - Assessment of adenoid size using an anaesthetic laryngoscope.

PMID- 21848565
TI  - The use of endotracheal tubes in the excision of troublesome paediatric
      suprastomal granulomas.

PMID- 21848566
TI  - Is out-of-hours experience out-of-touch?

PMID- 21848567
TI  - Inappropriate C-reactive protein testing in epistaxis patients.

PMID- 21848568
TI  - A pilot audit of paediatric ENT standards in London and Greater London: are we
      delivering a first class service?

PMID- 21848569
TI  - Re: Improving ENT trainees' training opportunity in percutaneous tracheostomy:
      how we do it.

PMID- 21848573
TI  - The effectiveness of community day-long CBT-I workshops for participants with
      insomnia symptoms: a randomised controlled trial.
AB  - Insomnia is a very common and disabling symptom. Whilst evidence for the efficacy
      of cognitive behavioural therapy for people diagnosed with insomnia (CBT-I) is
      strong, few people seek help and not many services offer CBT-I. Less intensive
      adaptations of CBT-I have been shown to be valuable, and given the size of the
      problem and low rates of help-seeking, an accessible intervention with a large
      capacity is needed. Day-long CBT-I psycho-educational workshops (each for up to
      30 people), to which members of the public with insomnia symptoms could self
      refer, have been developed. This randomised controlled trial aimed to evaluate
      the effectiveness of these workshops. Baseline measures were taken from 151
      participants, who were then randomised to experimental or waiting-list control
      groups. Scores of the experimental group and the control group were compared 3
      months after baseline. Random effects models found a significant interaction
      between time and group, indicating differences between the control and
      experimental groups on the Insomnia Severity Index (ISI). Post hoc analyses
      indicated that ISI scores decreased significantly in the experimental group, but
      not in the control group. Promising results were also found on corroborative
      sleep diary measures. Access to the workshops was good, with 50% of participants
      having never previously sought help for sleep difficulties from their GP. CBT-I
      workshops proved to be both accessible and effective in reducing insomnia
      symptoms in the medium term. They may represent a feasible brief intervention
      with the potential to address unmet treatment needs of adults complaining of
      insomnia symptoms.

PMID- 21848574
TI  - Assessment of the cardiac safety of prucalopride in healthy volunteers: a
      randomized, double-blind, placebo- and positive-controlled thorough QT study.
AB  - AIMS: To assess steady-state effects of therapeutic and supra-therapeutic doses
      of prucalopride on the QT interval using a novel design involving a parallel
      placebo group with nested crossover for positive control. METHODS: A double
      blind, double-dummy, placebo- and active-controlled study was conducted in 120
      healthy male and female volunteers (NCT00903747). Volunteers were randomized to
      receive prucalopride 2-10 mg once daily (therapeutic and supratherapeutic doses,
      respectively) (group 1), placebo with 400 mg moxifloxacin on day 1 (group 2a), or
      placebo with moxifloxacin on day 15 (group 2b). Twelve-lead 24 h Holter ECGs
      recorded at various time-points were evaluated blind and centrally. RESULTS:
      Estimated mean difference in study specific corrected QT interval (QT(c)SS) time
      matched change from baseline between prucalopride (2 and 10 mg) and placebo was
      <5 ms at all time points (maximum mean difference: 3.83 ms at 3.5 h post dose on
      day 5 with 2 mg [90% Cl -0.33, 6.38 ms]). Upper limits of the two-sided 90% CI
      for QT(c)SS were all <10 ms. There were no outlying QT(c)SS values >450 ms and no
      subjects had an increase >60 ms following prucalopride. Moxifloxacin produced the
      expected significant changes in QT(c)SS (>5 ms, maximum of +12.7 ms at 5 h post
      dose) at all time-points except 1 h post dose. Prucalopride resulted in small
      increases in heart rate (maximum of 5.8 beats min(-1)), which were similar for 2
      and 10 mg. Prucalopride was well tolerated after first day of treatment.
      CONCLUSION: Prucalopride at both therapeutic and supra therapeutic doses has no
      clinically significant effects on cardiac repolarisation in healthy volunteers.

PMID- 21848575
TI  - When to publish measures of disproportionality derived from spontaneous reporting
      databases?

PMID- 21848576
TI  - Burden and outcome of HIV infection and other morbidities in health care workers
      attending an Occupational Health Program at the Provincial Hospital of Tete,
      Mozambique.
AB  - OBJECTIVES: To investigate the burden and outcome of HIV infection and other
      morbidities amongst a Mozambican hospital staff. METHODS: Within an occupational
      health service set up in April 2008 in the provincial hospital of Tete,
      Mozambique, we offered to all staff members an initial clinical, laboratory and
      radiological screening and followed them up prospectively until April 2010.
      RESULTS: A total of 47.5% of 423 health workers attended the program. The cohort
      (female-to-male ratio: 2.2; mean age: 39 years) consisted mostly of auxiliary
      staff (43%) and nurses (29.8%). At initial screening, 71% were asymptomatic. HIV
      infection (28.4%) and tuberculosis (TB) (21%) were the main reported antecedent
      illnesses. Laboratory screening revealed anaemia (haemoglobin level <10 mg/dl) in
      9% participants, abnormal liver enzymes in 23.9% and a reactive non-treponemal
      syphilis test in 5%. Of 145 performed chest X-rays, 13% showed abnormalities. All
      113 health workers not recently tested for HIV were screened, and 31 were newly
      diagnosed with HIV infection (resulting in an overall HIV prevalence of 43.8%).
      Nine cases of TB were diagnosed at screening/during follow-up. In April 2010, all
      but one of the participants were alive. All HIV-infected health workers under
      antiretroviral therapy were actively followed-up. CONCLUSION: Serious conditions
      were frequently diagnosed in health workers, in particular HIV infection. Mid
      term outcome was favourable within this program. Creation of screening and care
      services dedicated to caregivers should be of highest priority in similar African
      settings.

PMID- 21848577
TI  - Evaluation of active tuberculosis case finding through symptom screening and
      sputum microscopy of close contacts in Shandong, China.
AB  - OBJECTIVES: To evaluate the effect of active case finding through symptom
      screening and sputum microscopy of close contacts in a Fidelis (Fund for
      Innovative DOTS Expansion through Local Initiatives to Stop TB) project. METHODS:
      Secondary data from all 35 counties were collected during implementation and
      used. They comprised new cases identified, number of close contacts screened and
      their relationships. Fifty-four in-depth interviews were conducted with staff
      from key stakeholders. RESULTS: A total of 13 310 symptomatic contacts of 5255
      index cases were screened, and 90 new smear-positive cases were detected with a
      yield rate of 0.7%. The yield rate of close contacts was positively associated
      with smear grades of the index cases (P<0.01). Close contacts of cases, such as
      classmates and workmates, who lived in a closed contained setting, had a higher
      yield rate than family members (P<0.001). Gaps in project implementation such as
      training, incentives and sputum collection were identified through in-depth
      interviews. CONCLUSIONS: The yield rate of close-contact screening of 0.7% was
      similar to other findings in China. There was a higher yield from screening of
      close contacts in congregated settings like schools and workshops. Future active
      case finding projects should provide clear operational guidelines and adequate
      training.

PMID- 21848578
TI  - Temporal changes in hospital costs for left ventricular assist device
      implantation.
AB  - BACKGROUND: A recent prospective, randomized controlled trial demonstrated that a
      continuous-flow (CF) left ventricular assist device (LVAD) resulted in improved
      survival at 12 and 24 months compared to a pulsatile-flow (PF) device. The
      current study examines the hospitalization costs associated with treatment of New
      York Heart Failure Class IV patients when implanted with a CF LVAD and compares
      them to previously reported costs of a PF LVAD in the same population. METHODS:
      Hospital billing data were analyzed for CF LVAD patients in the HeartMate II
      Destination Therapy trial to determine costs associated with the implantation
      admission. Hospital charges were converted to costs using hospital specific cost
      to-charge ratios. Hospital costs were evaluated based on patient outcomes and
      compared to previously reported results from patients who received a pulsatile
      flow LVAD in Randomized Evaluation of Mechanical Assistance for the Treatment of
      Congestive Heart Failure. Multivariate models were created to determine the
      primary determinates of cost. RESULTS: Hospital bills were available for 83 CF
      and 52 PF LVAD patients. Hospital length of stay and in-hospital mortality were
      lower in the CF cohort. Inflation-adjusted hospital costs were significantly
      lower for CF patients compared to PF patients (mean: $193,812 vs. $384,260, p <
      0.001). Clinical factors that strongly influenced hospitalization costs included
      bleeding, respiratory failure, and infection. CONCLUSIONS: There has been a 50%
      reduction in the hospitalization cost associated with LVAD implantation since
      2001. Improvements in operative technique and postoperative management appear to
      play critical roles in the observed cost reduction. 

PMID- 21848579
TI  - Omission of a prior Glenn anastomosis is a risk factor for prolonged pleural
      drainage after the fenestrated extracardiac conduit Fontan procedure.
AB  - OBJECTIVE: Factors related to prolonged pleural drainage after the Fontan
      operation have not been clearly defined. We investigated perioperative variables
      to establish factors predicting operative morbidity including prolonged chest
      tube drainage. Also, we pursued the fate of the fenestration during the follow-up
      period. METHODS: We retrospectively reviewed 52 patients who had undergone a
      fenestrated extracardiac Fontan procedure between August 1998 and June 2008. The
      median age at the time of surgery was 34.8 (range: 18.5 ~ 156) months and the
      median body weight 13.2 kg (range: 9.5 ~ 33). A multivariable logistic regression
      model was used to compare demographic, anatomic, and physiological variables for
      postoperative morbidity. RESULTS: Operative mortality occurred in one patient
      (1.9%). The mean duration of respiratory support, chest tube drainage, and
      hospital stay was 13 hours (range: 4 to 328 hours), six days (range: 2 to 45
      days), and 16 days (range: 7 to 444 days), respectively. Statistically, an
      operation without previous bidirectional cavopulmonary shunt (OR 30, 95% CI 3.1
      to 289) was the only independent risk factor for prolonged pleural drainage.
      Aortic cross-clamp time was identified as a risk factor for prolonged mechanical
      ventilatory support. During a median follow-up at 62 months (range: 17 to 137
      months), there was one late death (1.9%). Twenty-two patients (43%) underwent
      intervention for fenestration closure. CONCLUSIONS: Previous bidirectional
      cavopulmonary shunt and shortened aortic cross-clamp time may reduce
      postoperative morbidity including prolonged chest tube drainage and mechanical
      ventilator support after the fenestrated extracardiac conduit Fontan procedure. 

PMID- 21848580
TI  - Hospital-based home care for children with cancer: a qualitative exploration of
      family members' experiences in Denmark.
AB  - The study aims to describe the experiences of a hospital-based home care
      programme in the families of children with cancer. Fourteen parents, representing
      10 families, were interviewed about their experiences of a hospital-based home
      care programme during a 4-month period in 2009 at a university hospital in
      Denmark. Five children participated in all or part of the interview. The
      interviews were transcribed verbatim and analysed using qualitative content
      analysis. The findings indicate that hospital-based home care enabled the
      families to remain intact throughout the course of treatment, as it decreased the
      strain on the family and the ill child, maintained normality and an ordinary
      everyday life and fulfilled the need for safety and security. According to family
      members of children with cancer, hospital-based home care support enhanced their
      quality of life during the child's cancer trajectory. Our study highlights the
      importance of providing hospital-based home care with consideration for the
      family members' need for the sense of security achieved by home care by
      experienced paediatric oncology nurses and regular contact with the doctor. In
      future studies, interviews with children and siblings could be an important
      source of information for planning and delivering care suited to the families'
      perceived needs.

PMID- 21848581
TI  - Why people choose to not use complementary therapies during cancer treatment: a
      focus group study.
AB  - While 50% of cancer patients use complementary therapies (CT) during treatment,
      few studies have examined why individuals choose not to use CT. This study aimed
      to address this gap in knowledge using a focus group methodology, where 36
      participants took part in one of eight groups; participants were recruited until
      saturation of themes was achieved. Three categories of participants were
      investigated: patients/recent survivors (n= 14); volunteers/advocates (n= 16),
      the majority of whom were also long-term survivors; and health professionals (n=
      6). Focus groups were digitally audio-recorded, transcribed, and coded
      thematically using NVivo software. Reasons for non-use fell into four broad
      themes: (1) Resource barriers, particularly the cost and lack of time; (2) fear
      and distrust, including the potential for drug interactions; (3) lack of
      evidence, including the unproven nature of many CT practices; and (4)
      satisfaction with conventional treatment. Two further themes related to the
      benefits of non-use and reasons for discontinuation. A sub-analysis indicated
      that reasons for non-use differed by CT category, with non-use being mentioned
      more frequently for biologically based and body-based therapies. Differences in
      understanding CT non-use emerged between patients, volunteers and health
      professionals. Findings have clinical implications regarding tailoring
      information for patients during and after cancer.

PMID- 21848582
TI  - Interpretation and acceptance of the term 'cancer survivor': a United Kingdom
      based qualitative study.
AB  - The concept of cancer survivorship and the term 'cancer survivor' remains widely
      interpreted. The aim is to explore the interpretations of the term 'cancer
      survivor' amongst British people living past a cancer diagnosis. We conducted an
      in-depth qualitative study of 40 people at least 5 years post-diagnosis of
      breast, colorectal or prostate cancer. Each interviewee was asked whether they
      felt they were a cancer survivor and interpretations of the term were explored.
      The majority of respondents did not endorse the term 'cancer survivor', and there
      was a wide variation in its interpretation. Those who accepted the term
      understood survivorship as a factual definition of having had cancer and
      survived. Most rejected the term because it implied a high risk of death that did
      not reflect their experience, that it suggested survival from cancer was
      dependent on personal characteristics, or that it meant they were cured despite
      the possibility of recurrence. Respondents felt 'cancer survivor' was a label
      that did not describe their identity or that it implied an advocacy role they did
      not want to take on. Researchers and policy makers in the UK should consider
      avoiding the term 'cancer survivor' in favour of descriptive terms when
      discussing this population.

PMID- 21848583
TI  - Systematic review of the effect of telmisartan on insulin sensitivity in
      hypertensive patients with insulin resistance or diabetes.
AB  - WHAT IS KNOWN AND OBJECTIVE: Telmisartan is an angiotensin receptor blocker (ARB)
      originally developed for the treatment of hypertension. It can also partially
      activate peroxisome proliferator-activated receptor (PPAR)-gamma, which may
      improve insulin sensitivity. This effect may prove useful in hypertensive
      patients with insulin resistance or diabetes mellitus. Such activity is more
      marked than that observed with other ARBs. This systematic review and meta
      analysis evaluated the benefit of telmisartan on insulin sensitivity compared
      with that of other ARBs in hypertensive patients who had either insulin
      resistance or diabetic states. METHODS: Clinical trials of telmisartan were
      identified through electronic searches (MEDLINE, CINAHL, Scopus, and The Cochrane
      Library) up to and including May 2011. Studies were included if they met the
      following inclusion criteria: (i) randomized controlled trials that compared
      telmisartan with other ARBs in hypertensive patients who had insulin resistance
      or type 2 diabetes mellitus; (ii) using telmisartan as an add-on therapy or a
      monotherapy for treating hypertension; and (iii) reporting fasting plasma glucose
      (FPG) and fasting plasma insulin (FPI), or homeostasis model assessment of
      insulin resistance (HOMA-IR), or adiponectin as an outcome measure. Treatment
      effect was estimated with the mean difference in the final value of FPG, FPI,
      HOMA-IR and adiponectin between the telmisartan and the control groups. RESULTS
      AND DISCUSSION: Eight trials involving a total of 763 patients met the inclusion
      criteria. Telmisartan was superior to other ARBs in reducing FPG level (mean
      difference, -8.63 mg/dL; 95% CI -12.29 mg/dL to -4.98 mg/dL; P < 0.00001) and
      increasing adiponectin level (mean difference, 0.93 MUg/dL; 95% CI 0.28 MUg/dL to
      1.59 MUg/dL; P = 0.005). At 80 mg dose, telmisartan may reduce FPI level and HOMA
      IR. WHAT IS NEW AND CONCLUSIONS: The available evidence suggests a beneficial
      effect of telmisartan in improving insulin sensitivity in hypertensive patients
      with insulin resistance or diabetes as demonstrated by the decrease in FPG and
      increase in adiponectin levels. The effect in decreasing FPG was greater with 80
      mg dose than with the 40 mg dose. FPI and insulin resistance may be improved with
      80 mg of telmisartan.

PMID- 21848584
TI  - Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of
      microalbuminuria.
AB  - OBJECTIVE: To study the activation of an inflammatory cascade through leukocyte
      mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in
      individuals with childhood onset type 1 diabetes. DESIGN AND METHODS: Seventy-six
      type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old
      were recruited. Type 1 diabetic patients (DM1) were considered to have good
      (DM1G) or poor (DM1P) glycemic control according to the values of glycated
      hemoglobin. TLR2, TLR4, MyD88, interleukin -1beta (IL-1beta), IL-6, and tumor
      necrosis factor alpha (TNF-alpha) mRNA expressions were measured in peripheral
      blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea,
      creatinine, albumin, and total protein serum levels were determined. Urinary
      albumin-to-creatinine ratio (ACR) was calculated. RESULTS: DM1 and DM1P patients
      showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose
      concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated
      hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2,
      MyD88, IL-1beta, IL-6, and TNF-alpha were higher in DM1 and TLR2, IL-1beta, and
      IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum
      albumin and total protein were lower, while serum urea and ACR were higher in
      comparison to NG (p < 0.05). However, these differences compared to NG were more
      pronounced in DM1P, which included nine individuals with microalbuminuria.
      CONCLUSIONS: Increased mRNA expression of TLR2, MyD88, and pro-inflammatory
      cytokines in leukocytes of patients with childhood onset type 1 diabetes
      indicates the development of a TLR2-mediated pro-inflammatory process, which may
      also be associated with an early inflammatory process in the kidney and the
      occurrence of microalbuminuria.

PMID- 21848585
TI  - Abnormal tau deposition in neurons, but not in glial cells in the cerebral tissue
      surrounding arteriovenous malformation.
AB  - We report an autopsy case of arteriovenous malformation (AVM) of the right
      frontal lobe in a 50-year-old man, in whom post mortem examination revealed
      massive tau deposition in the affected cerebral cortex. The patient was diagnosed
      as having AVM at the age of 21 years, and died of unknown cause at the age of 50
      years. Immunostaining with anti-phosphorylated tau antibody (AT8) revealed many
      NFTs and neuropil threads, but not glial tau accumulation, in the right frontal
      cortex surrounding the AVM. The NFTs and neuropil threads contained both 3-repeat
      and 4-repeat tau. Ultrastructurally, the NFTs consisted of paired helical
      filaments. In the other brain areas, a few NFTs were found in the parahippocampal
      gyrus. There was no amyloid deposition in the brain. A variety of disease
      conditions, including brain tumor, viral encephalitis, angioma and cervical
      spondylotic myelopathy, have been reported to show Alzheimer-type NFTs. The
      present findings indicate that abnormal tau deposition can occur in neurons, but
      not in glial cells, of the affected cerebral cortex surrounding AVM.

PMID- 21848586
TI  - An unusual intraventricular tumor.

PMID- 21848588
TI  - Unusual tau in MSA.

PMID- 21848587
TI  - Inactivation of a Plasmodium apicoplast protein attenuates formation of liver
      merozoites.
AB  - Malaria parasites undergo a population expansion inside the host liver before
      disease onset. Developmental arrest inside host hepatocytes elicits protective
      immune responses. Therefore, elucidation of the molecular mechanisms leading to
      mature hepatic merozoites, which initiate the pathogenic blood phase, also
      informs anti-malaria vaccine strategies. Using targeted gene deletion in the
      rodent model malaria parasite Plasmodium berghei, we show that a Plasmodium
      specific Apicoplast protein plays an important role for Liver Merozoite formation
      (PALM). While the resulting knockout mutants develop normally for most of the
      life cycle, merozoite release into the blood stream and the ability to establish
      an infection are severely impaired. Presence of a signature blood-stage antigen,
      merozoite surface protein 1 and normal apicoplast morphology indicate that the
      inability to finalize merozoite segregation is a direct consequence of loss of
      PALM function. Experimental immunization of mice with as few as two doses of
      palm(-) sporozoites can elicit sterile protection up to 110 days after final
      immunization. Our data establish that a tailor-made arrest in the final steps of
      hepatic merozoite formation can induce strong protective immune responses and
      that malaria parasites employ a distinct apicoplast protein for efficient
      formation of pre-erythrocytic merozoites.

PMID- 21848589
TI  - The introduction of an early warning signs journal in an adolescent inpatient
      unit.
AB  - Early warning signs are considered to be one of the many tools utilized by
      specialist early intervention practitioners and other mental health professionals
      to assist young people how to recognize a deterioration in their mental state or
      if a relapse is indicated. This article focuses on the role that early warning
      signs recognition has played in a Child and Adolescent inpatient setting in the
      form of a journal that is used to record a young person's personal journey by
      recording early warning signs to prevent a future relapse. Feedback on the use of
      the journal has been positive from the young people who have utilized the journal
      and it has also been viewed as a useful and practical framework to identify key
      symptoms that may potentiate a relapse into illness.

PMID- 21848590
TI  - Psychodrama: an innovative way of improving self-awareness of nurses.
AB  - The aim of this educational session was to form a group interaction model for
      improving the self-awareness of nurses via psychodrama. The structured group
      interaction session was conducted three times, with three separate groups, during
      the 'Intensive Care Nursing' training programme at a teaching hospital in Ankara.
      An assessment was made using the written records and observations of the group
      director and co-directors and feedback from nurses regarding the session. The
      nurses were highly motivated, adapting readily to the learning environment and
      following the instructions without difficulty. They were able to describe their
      personal experience with a specific patient and also to identify the fundamental
      emotion engendered by that interaction. Their feedback regarding the session was
      favourable. The psychodrama technique helped the nurses to understand themselves,
      to explore the perspective of others and to make the connection between their own
      thoughts/feelings and those of their patients. Psychodrama can be an effective
      teaching tool in addressing the communication issues that arise in nursing.

PMID- 21848591
TI  - Stigmatization of schizophrenia as perceived by nurses, medical doctors, medical
      students and patients.
AB  - Stigmatization of schizophrenia is widespread and its genetic explanation may
      potentially increase the stigma. The present study investigated whether seeing
      schizophrenia as a genetic or environmental disorder might influence perceived
      beliefs towards people with schizophrenia and whether social stigmatizing
      attitudes were differently perceived the 202 subjects who were recruited.
      Perceived social stigmatizing attitudes were compared among participants who read
      two vignettes depicting a person with schizophrenia. Then, the Standardized
      Stigmatization Questionnaire (SSQ) was administered. A genetic explanation of
      schizophrenia was more frequently associated with stigmatizing attitudes. Also,
      there were higher levels of perceived stigmatization in medical students and
      medical doctors than in other groups based on their social experience or
      background. However, the sample size was small and this was a non-experimental
      design; also the SSQ would benefit from more cross-validation. About half of the
      participants perceived stigmatizing social attitudes. Finally, considering
      schizophrenia as a genetic disorder influenced participants perception of other
      people's beliefs about dangerousness and unpredictability and people's desire for
      social distance.

PMID- 21848592
TI  - Potential severity of aggressive behaviour after acquired brain injury:
      implications for recording.
AB  - Aggression is a consequence of acquired brain injury that may necessitate
      admission to neurobehavioural services. The 'Overt Aggression Scale - Modified
      for Neurorehabilitation' (OAS-MNR) is a valid, reliable means of capturing this.
      A criticism of observational rating scales is they do not reflect factors like
      intent to harm which results in recording anomalies. 'Attacks' has been proposed
      as a measure which achieves this within psychiatric settings. Principal goals of
      this study are to determine the usefulness of measuring similar concepts in
      neurobehavioural services and further validating both scales. A total of 1066
      physical assaults were recorded in 6 weeks by 25 patients in an inpatient
      neurobehavioural programme using the OAS-MNR. Fifty incidents were also rated on
      Attacks. Convergent validity for using both measures in neurobehavioural services
      was found. Modifying OAS-MNR severity scores using one of two factors found to
      underlie Attacks produced an index that successfully discriminated incidents
      whose risk necessitated more intrusive intervention, which was not evident
      otherwise. Modifying scores that objectively reflect severity of physical
      assaults using measures of perceived intent should be a feature of observational
      recording scales such as the OAS-MNR. Ensuring robust inter-rater reliability
      will be essential in any development work.

PMID- 21848593
TI  - Recruitment and retention of Canadian undergraduate psychiatric nursing faculty:
      challenges and recommendations.
AB  - The education of psychiatric nurses in Canada has gradually evolved since its
      inception early in the 20th century. The most obvious advancement has been a move
      away from institutionally based training to undergraduate university preparation.
      Associated with this advancement is the ongoing challenge of recruiting and
      retaining qualified nurse educators. This essay addresses external factors (e.g.
      title disparity, association affiliation, societal perception of psychiatric
      nursing and professional identity) and internal factors (e.g. career transition
      and tenure and promotion) that influence faculty recruitment and retention.
      Existing challenges and recommendations designed to enhance recruitment and
      retention efforts are outlined.

PMID- 21848594
TI  - Displays of inappropriate sexual behaviour by patients with progressive cognitive
      impairment: the forgotten form of challenging behaviour?
AB  - Persons with progressive cognitive impairment such as dementia or Alzheimer's
      disease may display an array of challenging behaviours. For instance, levels of
      agitation and aggression have been reported as high as 33% in home-dwelling
      individuals and 80% in those residing in institutions. One form of challenging
      behaviour that may be displayed by this group is inappropriate sexual behaviour
      (ISB), but it is often overshadowed by other behaviours such as aggression.
      Inappropriate sexual behaviour involves any verbal of physical action of a sexual
      nature which is displayed in an inappropriate social context. Examples of ISB
      include: exposure of genitals in public/ward environments, 'groping' of nurses
      and masturbation in public areas. It has been estimated that the prevalence of
      ISB ranges from 2% to 17% of individuals with progressive cognitive impairment.
      Although it is less frequent than other challenging behaviours, it still may have
      significant deleterious effects on the victim's health. This paper is a review of
      the available literature on the nature, effects and management of ISB in persons
      with progressive cognitive impairment. Possible avenues for future research are
      also explored.

PMID- 21848595
TI  - Are parent-reported repetitive and restricted behaviours associated with
      psychological problems in pre-school-aged children?
AB  - This study surveys the association of restricted and repetitive behaviours in pre
      school children with their emotional and behavioural problems. Parents of 504 pre
      school children selected by cluster sampling participated and filled in the
      questionnaires including repetitive and restricted behaviour (RRB) scale and the
      Strengths and Difficulties Questionnaire. The parents reported repetitive and
      restrictive behaviours are gender-related in pre-school-aged children.
      Hyperactivity and emotional problems are significantly in association with all
      the four types of repetitive and restrictive behaviours. Prosocial problems score
      is in association with 'reaction to change' subscale score. Children with higher
      scores of conduct problems have higher rates of 'sensorimotor stereotypies',
      'reaction to change' and 'modulation insufficiency'. Pre-school children with a
      higher rate of RRBs are more hyperactive and have more emotional problems than
      those with lower rates of RRBs. Conduct problems are more common in children with
      'sensorimotor stereotypies', 'reaction to change' and 'modulation insufficiency'
      problems. Repetitive and restricted behaviours are associated with mental health
      problems in pre-school-aged children.

PMID- 21848596
TI  - Door locking and exit security measures on acute psychiatric admission wards.
AB  - Locking the exit doors of psychiatric wards is believed to reduce the risk of
      patients absconding. The aims of the study were to investigate both the
      prevalence of door locking and other exit security measures on UK admission
      wards, as well as whether door locking appears to be effective in keeping
      inpatients in. A cross-sectional survey on 136 acute psychiatric wards in the UK
      was conducted, in which a range of data on patients, staff, and conflict and
      containment events, including door locking and absconding, were collected from
      shift to shift during a period of 6 months. About one-third of the participating
      wards (30%) operated with their ward exit door permanently locked, whereas
      another third (34%) never locked the ward door. Univariate analyses suggested
      little association between exit security measures and absconding. A more robust
      multilevel statistical analysis, however, did indicate a reduction of about 30%
      of absconding rates when the ward door was locked the entire shift. Although
      locking the ward door does seem to reduce absconding to a certain extent, it far
      from completely prevents it. As it may be unrealistic to strive for a 100%
      absconding-proof ward, alternative measures for door locking to prevent
      absconding are discussed.

PMID- 21848597
TI  - Learning from the world of mental health care: nursing students' narratives.
AB  - This narrative study describes the substance of nursing students' learning in the
      area of mental health and their responses to the challenges of working in the
      psychiatric field. The data consisted of 39 critical incidents written by 20
      Finnish second-year nursing students during their 5-week mental health placement.
      The narrative analysis method was used in the data analysis and the configuration
      of three consistent learning storylines: self-awareness and self-esteem, the
      nurse-patient relationship and mental health care methods. The three storylines
      characterized the essence of the students' learning and their responses to the
      challenges of the psychiatric field during the placement. The students were
      actively exposed to complicated care situations and patient encounters in which
      they had to face their own emotions and test coping skills. It seems that the
      critical incident technique stimulated students' narrative skills and possibly
      sensitized them for listening at the stories of their future patients.

PMID- 21848598
TI  - The evaluation of an online orientation to rural mental health practice in
      Australia.
AB  - The aim of this study was to develop and evaluate an online, interprofessional
      education programme for clinicians commencing work in rural mental health
      services in New South Wales, Australia. Twenty-eight participants, including
      nurses, psychologists, social workers and occupational therapists, completed a 24
      week education programme (Introduction to Rural Mental Health Practice programme)
      that orientated clinicians to working in rural settings. The online programme
      included an orientation to online learning and clinical skills such as risk
      assessment, therapeutic communication and de-escalation skills applied in rural
      settings. Twenty-four participants provided pre- and post-evaluation responses
      that were matched and analysed using paired t-tests to identify any significant
      differences in mean scores across the domains of interest. Fifty per cent (n= 13)
      of participants had a background in nursing and 49% were allied health clinicians
      (psychologists, social workers and occupational therapists). Statistically
      significant improvements (P < 0.05) were detected in participant confidence in
      responding to common mental health problems, knowledge about the role of
      different services in rural mental health care, perceived safety of work and
      perceived self-efficacy in dealing with challenging or aggressive behaviours. The
      Introduction to Rural Mental Health Practice programme was successful in
      orienting clinicians to rural mental health but the small sample size highlights
      the need to evaluate the programme with a larger cohort of rural clinicians. The
      attrition at the early stages of the study highlights significant challenges in
      the retention of rural clinicians in online education programmes. Factors that
      promoted participation and retention included the provision of study leave and
      orientation to the online environment.

PMID- 21848599
TI  - A narrative review of studies of refusal of psychotropic medication in acute
      inpatient psychiatric care.
AB  - This paper offers a narrative review of the 22 studies of medication refusal in
      acute psychiatry. Because of varied definitions of medication refusal, diverse
      methodologies and few rigorous studies, it has not been possible to draw firm
      conclusions on the average rate of refusal of psychotropic medications in acute
      psychiatry. However, it is clear that medication refusal is common and leads to
      poor outcomes characterized by higher rates of seclusion, restraint, threats of,
      and actual, assaults and longer hospitalizations. There are no statistically
      significant differences between refusers and acceptors in gender, marital status
      and preadmission living arrangements. Although no firm conclusions on the
      influence of ethnicity, status at admission and diagnosis on refusal, the
      refusers are more likely to have higher number of previous hospitalizations and
      history of prior refusal. The review indicates that staff factors such as the use
      of temporary staff, lack of confidence in ward staff and ineffective ward
      structure are associated with higher rates of medication refusal. Comprehensive
      knowledge of why, and how, patients refuse medication is lacking. Research on
      medication refusal is still fragmented, of variable methodological quality and
      lacks an integrating model.

PMID- 21848600
TI  - The creation of a Dementia Nurse Specialist role in an acute general hospital.
AB  - Older people form the largest group occupying acute hospital beds and many of
      them will have undiagnosed mental health problems. The creation of a Dementia
      Nurse Specialist role in a district general hospital provided the opportunity to
      assess the extent of the previously unmet need among patients, carers and nursing
      staff. Over 30 patients were seen each month, while around 6 to 12 were diagnosed
      as having dementia. Other activities undertaken as part of the role included
      providing information and support for carers, and advice on management of
      behaviours and support for ward staff. The role also involved policy writing,
      pathway and local strategy planning, care plan development, and formal and
      informal teaching on dementia. It is argued that this fixed-term post
      demonstrated that a Dementia Nurse Specialist could provide significant input in
      an acute hospital setting, by improving the experience of hospitalization for
      vulnerable older people and their carers.

PMID- 21848601
TI  - The importance of family to youth living in violent communities.

PMID- 21848602
TI  - Three-dimensional morphology of heel fat pad: an in vivo computed tomography
      study.
AB  - Heel fat pad cushioning efficiency is the result of its structure, shape and
      thickness. However, while a number of studies have investigated heel fat pad
      (HFP) anatomy, structural behavior and material properties, no previous study has
      described its three-dimensional morphology in situ. The assessment of the
      healthy, unloaded, three-dimensional morphology of heel pad may contribute to
      deepen the understanding of its role and behavior during locomotion. It is the
      basis for the assessment of possible HFP morphological modifications due to
      changes in the amount or distribution of the loads normally sustained by the
      foot. It may also help in guiding the surgical reconstruction of the pad and in
      improving footwear design, as well as in developing a correct heel pad geometry
      for finite element models of the foot. Therefore the purpose of this study was to
      obtain a complete analysis of HFP three-dimensional morphology in situ. The right
      foot of nine healthy volunteers was scanned with computed tomography. A
      methodological approach that maximizes reliability and repeatability of the data
      was developed by building a device to lock the foot in a neutral position with
      respect to the scan planes during image acquisition. Scan data were used to
      reconstruct virtual three-dimensional models for both the calcaneus and HFP. A
      set of virtual coronal and axial sections were extracted from the three
      dimensional model of each HFP and processed to extract a set of one- and two
      dimensional morphometrical measurements for a detailed description of heel pad
      morphology. The tissue exhibited a consistent and sophisticated morphology that
      may reflect the biomechanics of the foot support. HFP was found to be have a
      crest on its anterior dorsal surface, flanges on the sides and posteriorly, and a
      thick portion that reached and covered the posterior surface of the calcaneus and
      the achilles tendon insertion. Its anterior internal portion was thinner and a
      lump of fat was consistently present in this region. Finally, HFP was found to be
      thicker in males than in females.

PMID- 21848603
TI  - Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis
      C.
AB  - BACKGROUND: Hepatitis C virus infection evolves into chronic progressive liver
      disease in a significant percentage of patients. Monocytes constitute a diverse
      group of myeloid cells that mediate innate and adaptive immune response. In
      addition to proinflammatory CD16+ monocytes, a Tie-2+ subgroup - Tie-2 expressing
      monocytes (TEMs) - that has robust proangiogenic potential has been recently
      defined. AIM: To study the heterogeneity of peripheral blood monocytes in chronic
      hepatitis C (CHC) patients and to examine their proposed pathophysiological roles
      on disease progression and response to antiviral therapy. METHODS: We studied
      CD16+ and Tie-2+ peripheral monocyte subpopulations in 21 healthy subjects and 39
      CHC patients in various stages of disease and responses to antiviral treatment
      using flow cytometry. Expression profiles of proangiogenic and tissue remodelling
      factors in monocyte supernatants were measured using ELISA and protein arrays.
      Intrahepatic expression of CD14, CD31 and Tie-2 was analysed using
      immunofluorescence. RESULTS: Increases of certain peripheral monocyte subsets
      were observed in the blood of CHC patients, wherein those cells with
      proinflammatory (CD16+) or proangiogenic (TEMs) potential expanded (P < 0.005,
      both). Notably, TEMs were significantly increased in nonresponders, particularly
      those with lower CD16 expression. In addition, many angiogenic factors were
      differentially expressed by peripheral monocytes from control or CHC patients,
      such as angiopoietin-1 and angiogenin (P < 0.05). Interestingly, intrahepatic
      TEMs were distinguished within portal infiltrates of CHC patients. CONCLUSIONS:
      These findings suggest for the first time the relevance of peripheral monocytes
      phenotypes for the achievement of response to treatment. Hence, the study of
      monocyte subset regulation might effect improved CHC prognoses and adjuvant
      therapies.

PMID- 21848604
TI  - Diagnosis and treatment of radiation port dermatophytosis of scalp: a case
      report.

PMID- 21848605
TI  - Identification of yeast isolated from dermatological patients by MALDI-TOF mass
      spectrometry.
AB  - Species identification of yeasts is based on biochemical (e.g. API ID 32 C(r),
      bioMerieux) and molecular biological approaches. As an alternative to DNA
      dependent methods, mass spectral analysis based identification of micro-organisms
      has become increasingly recognized. In a number of studies, matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been
      applied for the rapid classification and identification of micro-organisms. In
      this study, the applicability of MALDI-TOF MS for identifying yeasts isolated
      from dermatological patients was analysed and compared with the results from the
      API ID 32 C(r) system. Furthermore, sequencing the internal transcribed spacer
      (ITS) regions of the ribosomal DNA was employed as reference method. Candida (C.)
      albicans was isolated in 41.9% of all cases, C. parapsilosis in 20.3%, C.
      glabrata in 10.8%, and C. krusei in 6, 8.1%. Rarely isolated yeasts were Candida
      colliculosa, famata, guilliermondii, lusitaniae, and tropicalis as well as
      Geotrichum candidum, Rhodotorula mucilaginosa and Trichosporon mucoides. The
      MALDI TOF results were equal to the results gained by ITS sequence analysis in
      94%, whereas API ID 32 C(r) provided the correct diagnosis in 84.3% (of all
      cases). This lower identification rate is mostly referable to frequent
      misidentifications of C. krusei as C. inconspicua/norvegensis,Candida tropicalis,
      or Geotrichum capitatum. In contrast, all C. krusei strains were correctly
      identified by MALDI TOF MS. In conclusion, species identification by MALDI-TOF MS
      was proven to be consistent with ITS sequence analysis; the technique has a
      resolving power comparatively as high as ITS sequence analysis.

PMID- 21848606
TI  - Bartonella infective endocarditis of a prosthetic aortic valve with a subvalvular
      abscess.
AB  - A patient with a prosthetic aortic valve, and culture negative endocarditis
      caused by Bartonella henselae presented with nonspecific constitutional symptoms,
      skin rash, and then later developed acute renal failure. The patient underwent
      redo sternotomy, aortic root, and ascending aorta replacement with a homograft,
      which resolved his symptoms and the renal failure. 

PMID- 21848607
TI  - Pupillary responses and event-related potentials as indices of the orienting
      reflex.
AB  - This study examined skin conductance responses, the late positive complex of the
      event-related potential, and pupillary dilation responses as autonomic and
      central correlates of the orienting reflex (OR) in the context of indifferent and
      significant stimuli. In particular, we aimed to clarify the inconsistencies
      surrounding the pupillary dilation response as an OR index. An auditory
      dishabituation paradigm was employed, and physiological measures were recorded
      from 24 participants. Response decrement to a repeated stimulus, response
      recovery to a change stimulus, and subsequent dishabituation were assessed.
      Findings confirmed expectations that the skin conductance response and the late
      positive complex are indices of the OR. The pupillary dilation response, however,
      demonstrated an unexpected sensitivity to stimulus novelty only, while the
      prestimulus measure of tonic pupil diameter showed the significance effect that
      was expected of the phasic measure. Together, these findings argue against the
      suggestion that the pupillary dilation response is an OR index. The diverse
      results obtained from this experiment contribute to our understanding of the OR,
      and provide impetus for further research with a variety of paradigm
      manipulations.

PMID- 21848608
TI  - Expression of toll-like receptors 2, 4 and 9 is increased in gingival tissue from
      patients with type 2 diabetes and chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Broad evidence indicates that diabetes both increases
      the risk and hastens the progression of periodontal disease. Likewise, chronic
      inflammation or infections seem to provoke insulin resistance and thereby
      contribute to the development of diabetes and its complications. Innate immune
      responses, which appear to be altered in individuals with diabetes, are usually
      mediated by the recognition of pathogens through toll-like receptors (TLRs). The
      constitutive expression of some TLRs has been reported in healthy human gingival
      tissue. Interestingly, the expression of TLRs 2 and 4 is increased with the
      severity of periodontal disease. Considering that the inflammatory reaction is
      exacerbated in individuals with diabetes and periodontitis, we suspected that the
      expression of some TLRs might be increased in gingival tissue in these patients.
      MATERIAL AND METHODS: In this study, we analyzed, by immunofluorescence, the
      expression of TLRs 2, 3, 4 and 9 in gingival tissues from healthy individuals and
      from periodontal patients with or without type 2 diabetes. RESULTS: We found that
      the expression levels of TLRs 2, 3, 4 and 9 were higher in all periodontal
      patients than in healthy individuals. The expression of some TLRs was increased
      in subjects with periodontitis and diabetes relative to subjects with
      periodontitis but without diabetes; this increase in expression was found
      particularly in TLR2 and TLR9 in the connective tissue and in TLR4 at the
      epithelial region. CONCLUSION: These data suggest that the expression of these
      TLRs 2, 3, 4 and 9 in gingival tissue is higher in individuals with diabetes
      because its inflammatory reaction is exacerbated. Additionally, the expression of
      these TLRS is positively regulated with the severity of periodontal disease.

PMID- 21848609
TI  - Pectate lyase affects pathogenicity in natural isolates of Colletotrichum
      coccodes and in pelA gene-disrupted and gene-overexpressing mutant lines.
AB  - Colletotrichum coccodes (Wallr.) S. Hughes, the causal agent of black dot on
      potato and anthracnose on tomato, reduces yield and crop quality. We explored the
      role of secreted pectate lyase (PL), a cell wall-degrading enzyme, in the
      aggressiveness of C. coccodes. In vitro-cultivated highly aggressive isolates
      secreted immunologically detectable PL levels 6 h after transfer to secondary
      medium versus 12 h for mildly aggressive isolates, suggesting that secreted PL is
      a virulence factor. The gene encoding PL, CcpelA, was cloned and used for the
      genetic manipulation of highly (US-41 and Si-72) and mildly (Si-60) aggressive
      isolates. CcpelA gene-disrupted mutants showed reduced aggressiveness towards
      tomato fruits and impaired PL secretion and extracellular activity. Conversely,
      overexpression of CcpelA in the Si-60 isolate increased its aggressiveness and PL
      secretion. Comparison of CcpelA cloned from isolates US-41 and Si-60 revealed
      that both encode identical proteins, but differ in their promoters.
      Bioinformatics analysis for cis-acting elements suggested that the promoters of
      the US-41 and Si-60 isolates contain one and no AreA-binding site (GATA box),
      respectively. AreA has been suggested to be involved in fungal aggressiveness;
      therefore, CcpelA may be a key virulence factor in C. coccodes pathogenicity, and
      the differences in isolate aggressiveness might result from promoter activity.
      Quantitative reverse transcriptase-polymerase chain reaction analyses confirmed
      the higher level of CcpelA transcript in isolate US-41 versus Si-60.

PMID- 21848610
TI  - Outcomes of pregnant patients with Pap smears classified as atypical glandular
      cells.
AB  - OBJECTIVES: The incidence of cervical cancers increases with age. Due to the
      trend of increasing age of first pregnancy, abnormal Pap smears including those
      classified as atypical glandular cells (AGC) are being found more often in early
      pregnancy. Once invasive cancer is excluded, conservative management of squamous
      intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal
      management of AGC is not well established. The aim of our study was to evaluate
      the outcome of patients with AGC diagnosed from smears during pregnancy. METHODS:
      The study included 17 patients referred to us in early pregnancy with Pap smears
      reported as AGC: 11 not otherwise specified (AGC-NOS), five favour neoplasia (AGC
      FN) and one adenocarcinoma in situ (AIS). Thirty-one with high-grade SIL (HSIL)
      Pap smears confirmed on punch biopsy in early pregnancy comprised a control
      group. Human papillomavirus (HPV) positivity was found in seven patients with
      persistent AGC-NOS (including all four who had CIN3 postpartum). All the women
      were initially examined by expert colposcopy and those with AGC-FN or AIS smears
      also by transrectal ultrasound to exclude invasive endocervical cancer. Follow-up
      controls were carried out every 8-12 weeks and, if there were no signs of
      progression, revaluation was scheduled 6-8 weeks after delivery. RESULTS: The
      mean age of the women was 31.4 years. Conization in one patient in the study
      group was performed in the 16th week of pregnancy due to colposcopic signs of
      microinvasive squamous cell cancer confirmed on histology. Progression to
      invasive cancer was not found in any of the other 16 patients in the study group
      or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed
      postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study
      group and, in 77.4% (24/31) of patients in the control group. CONCLUSIONS:
      Conservative management of women with AGC in pregnancy is safe where invasive
      cancer is excluded. As histological verification of glandular pre-cancerous
      lesions by punch biopsy is not reliable and the postpartum regression rate cannot
      be determined precisely, conization should be performed in all cases with AGC-FN
      or AIS. Triage of persistent AGC-NOS with HPV testing is useful in distinguishing
      significant underlying lesions.

PMID- 21848611
TI  - The human gut microbiome: are we our enterotypes?

PMID- 21848612
TI  - Cold is cool, the human microbiota and taking multiple SIPs.

PMID- 21848614
TI  - Induction of interleukin (IL)-1beta, IL-10, IL-8 and immunoglobulin G by
      Porphyromonas gingivalis HmuY in humans.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis, an anaerobic gram-negative
      bacterium, is associated with chronic periodontitis. This study was undertaken to
      evaluate the production of interleukin (IL)-1beta, IL-8 and IL-10 by human
      peripheral blood mononuclear cells (PBMC) stimulated with P. gingivalis antigens
      and to assess the levels of serum immunoglobulin (Ig)G, IgA and IgG subclasses
      raised against P. gingivalis HmuY protein. MATERIAL AND METHODS: PBMC from
      patients with chronic periodontitis (CP) and from nonperiodontitis (NP) control
      subjects were stimulated with P. gingivalis antigens, and the cytokine levels in
      the culture supernatants were determined by ELISA. The specificity of serum
      antibodies raised against HmuY was analyzed by Western blotting and by ELISA.
      RESULTS: Compared with the NP controls, the CP patients produced higher levels of
      total serum IgG and IgG1 specific for P. gingivalis HmuY. No differences were
      found between CP and NP groups in the production of IL-1beta and IL-8 by PBMC
      stimulated with total P. gingivalis antigens. Only P. gingivalis
      lipopolysaccharide (LPS) induced higher levels of IL-10 in the CP group. Higher
      levels of IL-1beta and IL-10 were induced by HmuY than by other antigens derived
      from the wild-type P. gingivalis strains. In contrast, total antigens derived
      from the hmuY-deletion mutant strain induced the production of significantly
      higher levels of IL-8 and significantly lower levels of IL-1beta. CONCLUSION: Our
      data suggest that P. gingivalis HmuY may be considered an immunogenic protein
      associated with host-pathogen interactions.

PMID- 21848615
TI  - Reduced functional loads alter the physical characteristics of the bone
      periodontal ligament-cementum complex.
AB  - BACKGROUND AND OBJECTIVE: Adaptive properties of the bone-periodontal ligament
      tooth complex have been identified by changing the magnitude of functional loads
      using small-scale animal models, such as rodents. Reported adaptive responses as
      a result of lower loads due to softer diet include decreased muscle development,
      change in structure-function relationship of the cranium, narrowed periodontal
      ligament space, and changes in the mineral level of the cortical bone and
      alveolar jaw bone and in the glycosaminoglycans of the alveolar bone. However,
      the adaptive role of the dynamic bone-periodontal ligament-cementum complex to
      prolonged reduced loads has not been fully explained to date, especially with
      regard to concurrent adaptations of bone, periodontal ligament and cementum.
      Therefore, in the present study, using a rat model, the temporal effect of
      reduced functional loads on physical characteristics, such as morphology and
      mechanical properties and the mineral profiles of the bone-periodontal ligament
      cementum complex was investigated. MATERIAL AND METHODS: Two groups of 6-wk-old
      male Sprague-Dawley rats were fed nutritionally identical food with a stiffness
      range of 127-158 N/mm for hard pellet or 0.3-0.5 N/mm for soft powder forms.
      Spatio-temporal adaptation of the bone-periodontal ligament-cementum complex was
      identified by mapping changes in the following: (i) periodontal ligament collagen
      orientation and birefringence using polarized light microscopy, bone and cementum
      adaptation using histochemistry, and bone and cementum morphology using micro-X
      ray computed tomography; (ii) mineral profiles of the periodontal ligament
      cementum and periodontal ligament-bone interfaces by X-ray attenuation; and (iii)
      microhardness of bone and cementum by microindentation of specimens at ages 6, 8,
      12 and 15 wk. RESULTS: Reduced functional loads over prolonged time resulted in
      the following adaptations: (i) altered periodontal ligament orientation and
      decreased periodontal ligament collagen birefringence, indicating decreased
      periodontal ligament turnover rate and decreased apical cementum resorption; (ii)
      a gradual increase in X-ray attenuation, owing to mineral differences, at the
      periodontal ligament-bone and periodontal ligament-cementum interfaces, without
      significant differences in the gradients for either group; (iii) significantly (p
      < 0.05) lower microhardness of alveolar bone (0.93 +/- 0.16 GPa) and secondary
      cementum (0.803 +/- 0.13 GPa) compared with the higher load group insert bone =
      (1.10 +/- 0.17 and cementum = 0.940 +/- 0.15 GPa, respectively) at 15 wk,
      indicating a temporal effect of loads on the local mineralization of bone and
      cementum. CONCLUSION: Based on the results from this study, the effect of reduced
      functional loads for a prolonged time could differentially affect morphology,
      mechanical properties and mineral variations of the local load-bearing sites in
      the bone-periodontal ligament-cementum complex. These observed local changes in
      turn could help to explain the overall biomechanical function and adaptations of
      the tooth-bone joint. From a clinical translation perspective, our study provides
      an insight into modulation of load on the complex for improved tooth function
      during periodontal disease and/or orthodontic and prosthodontic treatments.

PMID- 21848617
TI  - Clinical factors predictive of PCR positive in pandemic H1N1 2009 influenza virus
      infection.
AB  - OBJECTIVE: Pandemic H1N1 2009 influenza virus (H1N1) has been spreading globally.
      Clinical features might be predictive and may be different among countries. Even
      though the PCR test is a confirmatory test for this viral infection, it is
      expensive and limited in most Thai health care facilities. We studied predictive
      factors of PCR positive in H1N1 suspected patients. METHODS: Consecutive patients
      who had influenza-like illness less than seven days and had been tested for H1N1
      by the real-time PCR method between May and July 2009 were enrolled. Clinical
      data was collected and compared between those who had positive and negative PCR
      tests. RESULTS: There were 6494 patients had flu-like symptoms. Of those, 166
      patients were done PCR test and 75 patients (45.18%) had positive PCR test. There
      were four predictors for positive PCR test including history of contact with
      confirmed H1N1 patients, headache, body temperature, and coryza with the adjusted
      odds ratio (95% confidence interval) of 2.84 (1.09-7.40), 6.25 (1.42-27.49), 1.69
      (1.08-2.66), and 0.31 (0.12-0.79), respectively. CONCLUSIONS: Clinical factors
      can be both suggestive and protective factors for H1N1 infection. These factors
      may be helpful in clinical practice to assess the possibility of the H1N1
      infection in people who are at risk; particularly in resource-limited health care
      facilities.

PMID- 21848619
TI  - Effect of cyclooxygenase inhibitors in a xenograft model of canine mammary
      tumours.
AB  - Inhibition of cyclooxygenase-2 (COX-2) represents a possible avenue for the
      prevention and/or treatment of some cancers. Our goal was to compare the effect
      of a selective inhibitor of COX-2, deracoxib, and a COX-1 and -2 inhibitor,
      piroxicam, on the growth of canine mammary tumours in a murine model. CMT-9 was
      used to induce xenografts in nude mice. Mice were treated with piroxicam (0.6 mg
      kg(-1)), deracoxib (6 mg kg(-1)) or a control solution. Tumour volumes between 0
      and 24 days post-treatment showed no significant difference between all groups. A
      second series of experiments was performed with a higher dose of piroxicam (0.9
      mg kg(-1)). Tumour volumes between 14 and 21 days post-treatment were
      significantly smaller in piroxicam-treated mice compared with controls. These
      results demonstrate that COX inhibition reduced the growth of canine mammary
      cancer xenografts in mice, suggesting that COX inhibitors could have a positive
      effect in dogs.

PMID- 21848616
TI  - Report of the 'mechanisms of lung injury and immunomodulator interventions in
      influenza' workshop, 21 March 2010, Ventura, California, USA.
AB  - The clinical course of influenza and the extent of lung injury are determined by
      both viral and host factors, as well as sometimes secondary bacterial infections
      and exacerbations of underlying conditions. The balance between viral replication
      and the host immune responses is central to disease pathogenesis, and the extent
      of lung injury in severe influenza infections may be due in part to overly
      exuberant or dysregulated innate inflammatory responses or sometimes deficient
      responses. Acute respiratory distress syndrome (ARDS) is the principal cause of
      respiratory failure associated with severe influenza. ARDS can be triggered by
      both direct lung insults (e.g. respiratory pathogens) and systemic insults (e.g.
      sepsis), and the lung damage is exacerbated by the inflammatory response
      associated with either infectious or non-infectious insults. This workshop aimed
      to review the current understanding of lung injury in acute influenza and
      describe cellular and molecular mechanisms of lung injury that are common to
      influenza and infections by other respiratory pathogens. In addition, therapeutic
      agents that target host response proteins and pathways were identified and
      investigational agents in development reviewed. A logical strategy would be to
      combine antiviral treatment with drugs that modify excessive host responses or
      supplement deficient ones. However, a better understanding of common cell
      signalling pathways associated with acute lung injury caused by influenza and
      other pathogens is necessary to understand immunopathologic causes of lung
      injury. This will help determine which immunomodulatory interventions might be
      useful, and to predict the appropriate timing and consequences of their use.

PMID- 21848620
TI  - Development of a questionnaire assessing health-related quality-of-life in dogs
      and cats with cancer.
AB  - Health-related quality-of-life (HRQoL) has been studied extensively in human
      medicine. There is currently no standard HRQoL evaluation for veterinary oncology
      patients. The aim of this study was to assess the practicality, usefulness and
      robustness, from a pet owner and clinician perspective, of a questionnaire for
      the assessment of HRQoL in canine and feline cancer patients. A HRQoL assessment
      entitled 'Cancer Treatment Form' and two questionnaires entitled 'Owner Minitest'
      and 'Clinician Minitest' were designed. The first and second were completed by
      owners of patients presenting to a veterinary oncology referral service and the
      third by attending clinicians. The 'Cancer Treatment Form' was well received by
      owners and clinicians and provided a valuable assessment of HRQoL with 98%
      (82/84) of owners reporting an accurate reflection of their pet's quality-of
      life. Following this, minor improvements to the form could be suggested prior to
      regular use in evaluation of clinical oncology patients.

PMID- 21848621
TI  - Generation of recombinant antibody fragments that target canine dendritic cells
      by phage display technology.
AB  - One of the main goals in cancer immunotherapy is the efficient activation of the
      host immune system against tumour cells. Dendritic cells (DCs) can induce
      specific anti-tumour immune responses in both experimental animal models and
      humans. However, most preclinical studies using small animal models show only
      limited correlation with studies carried out in clinical settings, whereas
      laboratory dogs naturally develop tumours that are biologically and
      histopathologically similar to their human counterparts. Here, we describe the
      generation and characterization of recombinant antibodies against canine DCs,
      isolated using the Tomlinson phage display system. We successfully isolated
      highly specific single-chain variable fragment (scFv) antibodies in a sequential
      three-step panning strategy involving depletion on canine peripheral blood
      mononuclear cells followed by positive selection on native canine DCs. This
      provides the basis for an antibody-based method for the immunological detection
      and manipulation of DCs and for monitoring antigen-specific immune responses.

PMID- 21848622
TI  - Epidermal growth factor enhances the malignant phenotype in canine mammary
      carcinoma cell lines.
AB  - Canine mammary gland tumours (CMTs) are the most common malignancies in female
      dogs. The receptor tyrosine kinase EGFR (erbb1), a receptor for epidermal growth
      factor (EGF) and related factors, mediates multiple oncogenic functions in human
      epithelial neoplasms. While previous studies have demonstrated EGFR expression in
      canine tumours, its function has not been studied in canine cancer. The purpose
      of this study was to determine the in vitro effects of EGF and vandetanib
      (ZD6474), a small molecule inhibitor of VEGFR-2, EGFR and RET tyrosine kinases,
      on proliferation, invasion, survival and chemosensitivity in CMT cells. In low
      serum, EGF enhanced proliferation and chemotaxis, attenuated apoptosis, and
      stimulated vascular endothelial growth factor (VEGF) production. Vandetanib dose
      dependently inhibited EGFR phosphorylation as well as PI3K/Akt activation, and
      inhibited all EGF-induced phenotypic effects. In conclusion, EGF stimulates
      multiple features promoting the malignant phenotype in CMT. Thus, CMT may be an
      important translational model for the investigation of novel EGFR-directed
      therapies.

PMID- 21848623
TI  - Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine
      osteosarcoma cells.
AB  - The development of metastasis is the most significant cause of death for both
      canine and human patients with osteosarcoma (OS). Ezrin has been associated with
      tumour progression and metastasis in human, canine and murine OS. Ezrin
      activation is dynamically regulated by protein kinase C (PKC) during metastatic
      progression in human and murine OS. To include the dog in the development of
      therapeutics that target ezrin biology, we characterized four new canine OS cell
      lines and confirmed the relationship between PKC and ezrin in these cells. Three
      of four cell lines formed tumours in mice that were histologically consistent
      with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC.
      Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC
      inhibitor. These data suggest that an association between PKC-mediated activation
      of ezrin and the metastatic phenotype in canine OS cells.

PMID- 21848624
TI  - Analysis of KIT expression and KIT exon 11 mutations in canine oral malignant
      melanomas.
AB  - KIT, a transmembrane receptor tyrosine kinase, is one of the specific targets for
      anti-cancer therapy. In humans, its expression and mutations have been identified
      in malignant melanomas and therapies using molecular-targeted agents have been
      promising in these tumours. As human malignant melanoma, canine malignant
      melanoma is a fatal disease with metastases and the poor response has been
      observed with all standard protocols. In our study, KIT expression and exon 11
      mutations in dogs with histologically confirmed malignant oral melanomas were
      evaluated. Although 20 of 39 cases were positive for KIT protein, there was no
      significant difference between KIT expression and overall survival. Moreover,
      polymerase chain reaction amplification and sequencing of KIT exon 11 in 17
      samples did not detect any mutations and proved disappointing. For several
      reasons, however, KIT expression and mutations of various exons including exon 11
      should be investigated in more cases.

PMID- 21848625
TI  - Comparison of two questionnaires to assess gastrointestinal toxicity in dogs and
      cats treated with chemotherapy*.
AB  - Questionnaires completed by pet owners are widely used instruments to monitor
      adverse gastrointestinal (GI) effects in the owners' animals undergoing
      chemotherapy and for reporting toxicoses in clinical trials; however, no
      questionnaires have been formally evaluated. This study compares two
      questionnaire-based evaluations of adverse GI events: a basic, open-ended
      questionnaire and a detailed questionnaire modelled after the grading in the
      Veterinary Co-operative Oncology Group-Common Terminology Criteria for Adverse
      Events (VCOG-CTCAE). Owners completed both questionnaires after their dog or cat
      received moderately emetogenic chemotherapy. Results were used to derive toxicity
      grades for anorexia, vomiting and diarrhoea. We evaluated 123 pairs of
      questionnaires. Disagreement in grade of anorexia, vomiting and diarrhoea was
      found in 24, 7 and 13% of paired questionnaires, respectively (kappa = 0.63, 0.83
      and 0.71, respectively). Although 'good' to 'very good' agreement was found, the
      potential for only 'fair' agreement between questionnaire methods is of concern
      and suggests a need to adopt a standardized form.

PMID- 21848626
TI  - Radiosensitivity and capacity for radiation-induced sublethal damage repair of
      canine transitional cell carcinoma (TCC) cell lines.
AB  - Understanding the inherent radiosensitivity and repair capacity of canine
      transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to
      treat this disease. The objective of this study was to evaluate the parameters
      surviving fraction at 2 Gy (SF(2) ), alpha/beta ratio and capacity for sublethal
      damage repair (SLDR) in response to radiation. Dose-response and split-dose
      studies were performed using the clonogenic assay. The mean SF(2) for three
      established TCC cell lines was high at 0.61. All the three cell lines exhibited a
      low to moderate alpha/beta ratio, with the mean being 3.27. Two cell lines
      exhibited statistically increased survival at 4 and 24 h in the dose-response
      assay. Overall, our results indicate that the cell lines are moderately
      radioresistant, have a high repair capacity and behave similarly to a late
      responding normal tissue. These findings indicate that the radiation protocols
      utilizing higher doses with less fractionation may be more effective for treating
      TCC.

PMID- 21848627
TI  - The role of rectal chloride secretion in childhood constipation.
AB  - BACKGROUND: Disturbance in fluid secretion, driven by chloride secretion, might
      play a role in constipation. However, disturbed chloride secretion in those
      patients has yet to be evaluated. Therefore, the aim of this study was to compare
      chloride secretion in rectal biopsies of children with functional constipation
      (FC) to those without constipation. METHODS: To measure changes in short circuit
      current (I(sc) in MUA cm(-2)) reflecting chloride secretion, intestinal biopsies
      from children with constipation, to either exclude or diagnose Hirschsprung's
      disease, and from children without constipation (controls) undergoing colonoscopy
      for screening of familial adenomatous polyposis, juvenile polyps or inflammatory
      bowel disease (IBD), were compared and studied in Ussing chambers. Following
      electrogenic sodium absorption blockade by amiloride, chloride secretory
      responses to calcium-linked (histamine, carbachol) and cAMP-linked
      (IBMX/forskolin) secretagogues were assessed. KEY RESULTS: Ninety-six patients
      (46 FC) participated; nine FC patients (n = 1 congenital syndrome and n = 8
      technical problems) and 13 controls (n = 6 IBD; n = 7 technical problems) were
      excluded. No significant difference was found in mean (+/-SE) basal chloride
      currents between children with FC and controls (9.6 +/- 1.1 vs 9.2 +/- 0.8; P =
      0.75, respectively). Responses to calcium-linked chloride secretagogues
      (histamine and carbachol) were significantly higher in controls (33.0 +/- 3.0 vs
      24.5 +/- 2.3; P = 0.03 and 33.6 +/- 3.4 vs 26.4 +/- 2.7; P = 0.05 following
      histamine and carbachol, respectively). CONCLUSIONS & INFERENCES: Calcium-linked
      chloride secretion is disturbed in children with FC. Whether this defect occurs
      at the level of histamine receptors, components of receptor-linked signal
      transduction pathways or basolateral Ca(2+) -sensitive K(+) channels enhancing
      the electrical driving force for apical chloride secretion, remains to be
      explored.

PMID- 21848628
TI  - Exposure to hookworms in patients with Crohn's disease: a case-control study.
AB  - BACKGROUND: Helminths have been used to inhibit intestinal inflammation in
      patients with Crohn's disease. AIM: This study was undertaken to determine if
      there is a protective association of prior hookworm infection with Crohn's
      disease, in a region where there is epidemiological transition from parasitic and
      infectious diseases to increased auto-inflammatory diseases. METHODS: Hookworm
      exposure was assessed by peripheral blood mononuclear cell (PBMC) activation by
      hookworm antigens in 78 patients with Crohn's disease and 75 healthy control
      participants. The change in proportion of T cells exhibiting CD69 after exposure
      to crude hookworm antigens was measured. Interferon-gamma ELISPOT response to a
      panel of six recombinant hookworm antigens was analysed. RESULTS: Patients with
      Crohn's disease were more often from an urban background (P=0.005) compared to
      controls, while their socioeconomic status was not significantly different. T
      cell activation (increase in CD3(+) CD69(+) population) by hookworm antigen was
      significantly higher in controls compared to Crohn's disease patients (P=0.017),
      while activation by the nonspecific mitogen phytohemagglutinin was similar in
      both groups. Circulating T memory cells (CD3(+) CD45RO(+)) after exposure to
      hookworm antigens were not significantly different between the two groups.
      Mirroring these changes, interferon-gamma ELISPOT responses to hookworm antigens
      were seen in 36 of 75 controls compared to 20 of 78 Crohn's disease patients
      (Fisher's exact P=0.005). Multivariate analysis indicated that CD3CD69 shifts
      (P=0.019), ELISPOT reactivity (P=0.039) and place of residence (P=0.024) were all
      independently associated with Crohn's disease. CONCLUSION: The inverse
      association between Crohn's disease and hookworm antigen reactivity is consistent
      with the hygiene hypothesis, but requires further exploration.

PMID- 21848629
TI  - Increasing insulin resistance is associated with increased severity and
      prevalence of gastro-oesophageal reflux disease.
AB  - BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) is based on
      reflux symptoms. Although metabolic syndrome has been linked to erosive
      oesophagitis (EO), the impact of insulin resistance, the core of the metabolic
      syndrome, on reflux symptoms remains to be elucidated. AIM: To assess the effects
      of insulin resistance on GERD, including both endoscopic findings and symptoms.
      METHODS: A total of 743 sonographic noncirrhotic adult subjects, who underwent an
      upper gastrointestinal endoscopic examination, completed a gastro-oesophageal
      reflux questionnaire and had available fasting insulin data were included.
      Endoscopic findings were classified according to the Los Angeles classification.
      Homeostatic model assessment-insulin resistance (HOMA-IR) index was used to
      evaluate the status of insulin resistance. Univariate and multivariate approaches
      were used to evaluate the associations between insulin resistance and GERD.
      RESULTS: Older age, male gender, smoking and alcohol consumption increased the
      prevalence of EO, but not GERD symptoms. A large waist circumference, high
      fasting blood glucose levels and high number of metabolic syndrome components
      were associated with increased prevalence of both EO and GERD symptoms, while
      high blood pressure was associated with increased prevalence of EO only.
      Moreover, higher scores in the gastro-oesophageal reflux questionnaire were
      associated with higher HOMA-IR index, and higher HOMA-IR index was associated
      with increased prevalence of EO (adjusted odds ratio 1.14, 95% CI 1.03-1.26, P =
      0.012). CONCLUSIONS: Our findings demonstrate clear associations between insulin
      resistance, metabolic syndrome and GERD. Whether reducing insulin resistance may
      improve GERD symptoms or EO deserves prospective study.

PMID- 21848630
TI  - Review article: an analysis of the efficacy, perforation rates and methods used
      in pneumatic dilation for achalasia.
AB  - BACKGROUND: Pneumatic dilation has re-emerged as a first line treatment for
      achalasia, but conclusions are limited by the relatively small numbers of
      patients studied and the lack of long term follow-up. AIM: To summarise and
      analyse 29 available studies evaluating pneumatic dilation for achalasia with
      focus on efficacy, rate or perforation and dilation technique. METHODS: A
      literature search for all studies, in which pneumatic dilation was performed for
      treatment of achalasia, was conducted. Studies, in which clear endpoints of
      efficacy of single dilation sessions over a period of years, were chosen.
      RESULTS: The response for a single dilation session was 66% at 1 year and 59, 53,
      50 and 25% at 2, 3, 5 and 10 years respectively. Use of a Rigiflex dilator and
      multiple dilations during the initial treatment improved efficacy. Overall
      perforation rate was only 2% (24/1358) of which only 1% required surgery. Use of
      multiple dilations led to increased perforation risk. The method of dilation used
      with regard to balloon size, pressure used, dilation times and single or multiple
      dilations varied in almost every study. CONCLUSIONS: Pneumatic dilation is safer
      than commonly thought and efficacious, although multiple dilations will be needed
      over a lifetime in most patients. Standardisation of the technique should be
      attempted.

PMID- 21848631
TI  - Interstitial cystitis symptoms associated with ketamine abuse: the first Japanese
      case.

PMID- 21848632
TI  - Catheter ablation of idiopathic ventricular tachycardia originating from
      myocardial extensions into a noncoronary aortic cusp.
AB  - We present a 34-year-old woman with idiopathic ventricular tachycardia that
      resisted 2 previous attempts for catheter ablation and was successfully ablated
      in the myocardial extension within the noncoronary aortic cusp.

PMID- 21848633
TI  - Radiofrequency ablation complicated by left atrial intramural hematoma.

PMID- 21848634
TI  - Walking the tightrope between deep sedation and general anesthesia: by whom can
      this safely be done?

PMID- 21848635
TI  - Identification of unusual reentry circuit sites of nonischemic ventricular
      outflow tract tachycardia.
AB  - BACKGROUND: Reentrant ventricular outflow tract (OT) tachycardia is rare in
      patients with nonischemic heart disease. The mechanism of ventricular tachycardia
      (VT) arising from the region of the aortic sinus of Valsalva (ASOV) is usually
      focal, rather than reentrant. Consequently, less is known about reentrant
      circuits in the OT and the aortic sinuses. The purpose of this study was to
      evaluate existence of reentry circuits in these areas using entrainment mapping
      techniques. METHODS: We performed electrophysiological study in 51 consecutive
      patients with idiopathic or nonischemic symptomatic VT arising from the OT. Six
      of these patients were found to have VT of reentrant mechanism with 8 VT
      morphologies. Entrainment mapping, electroanatomical mapping (in 2 patients), and
      radiofrequency catheter ablation were performed. RESULTS: Pacing entrained the VT
      at 93 sites, 52 of which were determined to be in the reentry circuit based on
      matching of the postpacing interval and VT cycle length. Of the reentry circuit
      sites, 6 were in the aortic sinus, 43 were below the aortic valve, and 3 were in
      the right OT below the pulmonary valve. Classification of reentry circuit sites
      identified 7 as exit, 1 as central-proximal, 19 as inner loop, and 25 as outer
      loop sites. Catheter ablation terminated VT at 4 of the 6 aortic sinus sites and
      4 of the 46 OT sites (P = 0.0006). CONCLUSIONS: We definitively demonstrated
      involvement of the ASOV in OT reentrant tachycardia using entrainment mapping. It
      may be useful for successful VT ablation to identify reentry circuit
      localization.

PMID- 21848636
TI  - Towards secondary prevention of Type 1 diabetes.

PMID- 21848637
TI  - Caveat emptor: implantable devices in end-stage renal disease.

PMID- 21848638
TI  - Pumping ions.
AB  - 1. This is a concise review of the field of ion pumping from the perspective of
      the authors. 2. The period covered spans the discovery of Na(+)  and K(+) 
      concentration gradients across animal cell membranes by Carl Schmidt in the
      1850s, through the isolation of the Na(+) /K(+) -ATPase by Skou in 1957 (for
      which he was awarded the 1997 Nobel Prize in Chemistry), to the publication of
      the first crystal structure of the enzyme in 2007 and beyond. 3. Contributions of
      the authors' research group to the resolution of the questions of the mechanism
      of the allosteric role of ATP within the Na(+) /K(+) -ATPase reaction cycle and
      how protomeric versus diprotomeric states of the enzyme influence its kinetics
      are discussed within the context of the research field. 4. The results obtained
      indicate that the Na(+) /K(+) -ATPase has a single ATP binding site, which can be
      catalytic or allosteric in different parts of the enzyme's reaction cycle. 5. The
      long-running controversy over whether P-type ATPases function as protomers or
      diprotomers can be resolved in the case of the Na(+) /K(+) -ATPase by an ATP
      induced dissociation of (alphabeta)(2)  diprotomers into separate alphabeta
      protomers. 6. Kinetic data suggest that protein-protein interactions between the
      two alphabeta protomers within an (alphabeta)(2)  diprotomer result in a much
      lower enzymatic turnover (i.e. a lower gear) when only one of the alpha-subunits
      of the diprotomer has bound ATP. The inactive alphabeta protomer within the
      diprotomer can be thought of as causing a drag on the active protomer.

PMID- 21848639
TI  - Effect of 5-HT2A receptor antagonists on human platelet activation in blood
      exposed to physiologic stimuli and atherosclerotic plaque.

PMID- 21848640
TI  - Evidence for heterogeneity of the obstetric antiphospholipid syndrome: thrombosis
      can be critical for antiphospholipid-induced pregnancy loss.
AB  - BACKGROUND: Antiphospholipid antibodies are associated with thrombosis and
      repeated pregnancy losses during the antiphospholipid syndrome. Several
      experimental findings indicate that purified antiphospholipid antibodies are
      directly responsible for inflammation-induced pregnancy losses, or for disruption
      of the annexin A5 shield at the trophoblastic interface. We previously showed
      that passive transfer of CIC15, a monoclonal antiphospholipid antibody binding to
      cardiolipin and annexin A5 that was isolated from a patient with primary
      antiphospholipid syndrome, induces fetal resorption in pregnant mice. OBJECTIVES:
      To investigate the mechanisms of CIC15-induced pregnancy loss. METHODS/RESULTS:
      We show that CIC15 induces fetal loss through a new mechanism that is probably
      related to procoagulant activity. The time course is different from those of
      previously described models, and histologic analysis shows that the placentas are
      devoid of any sign of inflammation but display some signs of thrombotic events.
      Despite these differences, the CIC15 and 'inflammatory' models share some
      similarities: lack of FcgammaRI/III dependency, and the efficacy of heparin in
      preventing fetal losses. However, this latter observation is here mostly
      attributable to anticoagulation rather than complement inhibition, because
      fondaparinux sodium and hirudin show similar efficiency. In vitro, CIC15 enhances
      cardiolipin-induced thrombin generation. Finally, using a combination of surface
      sensitive methods, we show that, although it binds complexes of cardiolipin
      annexin A5, CIC15 is not able to disrupt the two-dimensional ordered arrays of
      annexin A5. CONCLUSIONS: This human monoclonal antibody is responsible for
      pregnancy loss through a new mechanism involving thrombosis. This mechanism adds
      to the heterogeneity of the obstetric antiphospholipid syndrome.

PMID- 21848641
TI  - Relative contributions of stromal interaction molecule 1 and CalDAG-GEFI to
      calcium-dependent platelet activation and thrombosis.
AB  - BACKGROUND: Stromal interaction molecule 1 (STIM1) was recently identified as a
      critical component of store-operated calcium entry (SOCE) in platelets. We
      previously reported the Ca(2+) -sensing guanine nucleotide exchange factor CalDAG
      GEFI as a critical molecule in Ca(2+) signaling in platelets. OBJECTIVE: To
      evaluate the contribution of STIM1/SOCE to Ca(2+) -dependent platelet activation
      and thrombosis, we here compared the activation responses of platelets lacking
      STIM1 and platelets lacking CalDAG-GEFI. METHODS: The murine Stim1 gene was
      conditionally deleted in the megakaryocyte/platelet lineage. CalDAG-GEFI(-/-) and
      Stim1(fl/fl) PF4-Cre mice, along with littermate control mice, were used for in
      vitro and in vivo experiments under flow as well as static conditions. RESULTS:
      Integrin alpha(IIb) beta(3) -mediated aggregation was markedly impaired in CalDAG
      GEFI-deficient but not STIM1-deficient platelets, under both static and flow
      conditions. In contrast, deficiency in either STIM1 or CalDAG-GEFI significantly
      impaired the ability of platelets to express phosphatidylserine on the cell
      surface. When subjected to a laser injury thrombosis model, mice lacking STIM1 in
      platelets were characterized by the formation of unstable platelet-rich thrombi
      and delayed and reduced fibrin generation in injured arterioles. In CalDAG-GEFI(
      /-) mice, fibrin generation was also delayed and reduced, but platelet
      accumulation was almost abolished. CONCLUSIONS: Our studies suggest that: (i)
      STIM1/SOCE is critical for the procoagulant activity but not the proadhesive
      function of platelets; and (ii) at the site of vascular injury, STIM1 and CalDAG
      GEFI are critical for the first wave of thrombin generation mediated by
      procoagulant platelets.

PMID- 21848642
TI  - Plasminogen activator inhibitor type I contributes to protective immunity during
      experimental Gram-negative sepsis (melioidosis).
AB  - BACKGROUND: Melioidosis is a frequent cause of sepsis in Southeast Asia caused by
      the Gram-negative bacterium Burkholderia pseudomallei. Patients with melioidosis
      have elevated circulating levels of plasminogen activator inhibitor type 1 (PAI
      1), an important regulator of inflammation and fibrinolysis. OBJECTIVES: In this
      study, we aimed to investigate the role of PAI-1 during melioidosis. METHODS:
      Wild-type (WT) and PAI-1-deficient (PAI-1-/1(-/-) ) mice were intranasally
      infected with B. pseudomallei. Mice were killed after 24, 48 or 72 h. Lungs,
      liver and blood were harvested for measurement of bacterial loads, cytokines,
      clinical chemistry, histopathology, and coagulation parameters. Additionally,
      survival studies were performed. RESULTS: PAI-1(-/-) mice demonstrated enhanced
      susceptibility to B. pseudomallei infection, as shown by a strongly increased
      mortality rate (100% vs. 58% among WT mice, P < 0.001), associated with enhanced
      bacterial loads in lungs, liver, and blood. Additionally, PAI-1(-/-) mice showed
      elevated levels of proinflammatory cytokines in lungs and plasma, accompanied by
      enhanced local and systemic coagulation activation (thrombin-antithrombin
      complexes and D-dimer), increased hepatocellular injury (plasma aspartate
      aminotransferase and alanine aminotransferase), and renal failure (plasma
      creatinine and urea). CONCLUSIONS: PAI-1 has a protective role during severe Gram
      negative sepsis caused by B. pseudomallei by limiting bacterial growth,
      inflammation, and coagulation, and probably, as a consequence thereof, distant
      organ injury.

PMID- 21848643
TI  - Upregulation of Ras/Raf/ERK1/2 signaling and ERK5 in the brain of autistic
      subjects.
AB  - Autism is a neurodevelopmental disorder characterized by impairments in social
      interaction, verbal communication and repetitive behaviors. A number of studies
      have shown that the Ras/Raf/ERK1/2 (extracellular signal-regulated kinase)
      signaling pathway plays important roles in the genesis of neural progenitors,
      learning and memory. Ras/Raf/ERK1/2 and ERK5 have also been shown to have death
      promoting apoptotic roles in neural cells. Recent studies have shown a possible
      association between neural cell death and autism. In addition, two recent studies
      reported that a deletion of a locus on chromosome 16, which included the mitogen
      activated protein kinase 3 (MAPK3) gene that encodes ERK1, is associated with
      autism. Most recently, our laboratory detected that Ras/Raf/ERK1/2 signaling
      activities were significantly enhanced in the brain of BTBR mice that model
      autism, as they exhibit many autism-like behaviors. We thus hypothesized that
      Ras/Raf/ERK1/2 signaling and ERK5 could be abnormally regulated in the brain of
      autistic subjects. In this study, we show that the expression of Ras protein was
      significantly elevated in the frontal cortex of autistic subjects. C-Raf
      phosphorylation was increased in the frontal cortex, while both C-Raf and A-Raf
      activities were enhanced in the cerebellum of autistic subjects. We also detected
      that both the protein expression and activities of ERK1/2 were significantly
      upregulated in the frontal cortex of autistic subjects, but not in the
      cerebellum. Furthermore, we showed that ERK5 protein expression is upregulated in
      both frontal cortex and cerebellum of autistic subjects. These results suggest
      that the upregulation of Ras/Raf/ERK1/2 signaling and ERK5 activities mainly
      found in the frontal cortex of autistic subjects may be critically involved in
      the pathogenesis of autism.

PMID- 21848644
TI  - Antibacterial activity of different degree of hydrolysis of palm kernel expeller
      peptides against spore-forming and non-spore-forming bacteria.
AB  - AIMS: The goal of this study was to determine inhibitory effect of palm kernel
      expeller (PKE) peptides of different degree of hydrolysis (DH %) against spore
      forming bacteria Bacillus cereus, Bacillus circulans, Bacillus coagulans,
      Bacillus licheniformis, Bacillus megaterium, Bacillus pumilus, Bacillus
      stearothermophillus, Bacillus subtilis, Bacillus thuringiensis, Clostridium
      perfringens; and non-spore-forming bacteria Escherichia coli, Lisinibacillus
      sphaericus, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella
      Typhimurium and Staphylococcus aureus. METHODS AND RESULTS: A range of DH % (50
      100) of PKE peptides was prepared using alcalase, and hydrolysis conditions were
      determined using response surface methodology (RSM). The influence of pH (6.5
      10.5), temperature (35-65 degrees C), enzyme/substrate ratio (1-5%) and substrate
      concentration (1-2%) were studied on the response of the DH. The antibacterial
      activity of different DH % of PKE peptides was tested by using disc diffusion
      assay and micro-broth dilution assay. According to the minimum inhibitory
      concentration (MIC) test on each of the PKE peptides of different DH %, the 70 DH
      % PKE peptide showed greater inhibitory effect compared to the 100 DH % PKE
      peptide against B. cereus, B. coagulans, B. megaterium, B. pumilus, B.
      stearothermophillus, B. subtilis, B. thuringiensis, Cl. perfringens,
      Lisinibacillus sphaericus and L. monocytogenes. CONCLUSIONS: The 70 DH % PKE
      peptides exhibited greatest overall antibacterial effect of the various peptides
      of PKE evaluated. Further research is needed to determine the mode of action of
      PKE peptides. SIGNIFICANCE AND IMPACT OF THE STUDY: Palm kernel expeller
      peptides, a natural plant product, effectively inhibited the growth of spore
      forming and non-spore-forming Gram-positive bacteria. Potentially, PKE peptides
      could be used in food preservation and developed as antibacterial agent in the
      pharmaceutical industry.

PMID- 21848645
TI  - Are serum TSH levels associated with oxidized low-density lipoprotein? Results
      from the Study of Health in Pomerania.
AB  - OBJECTIVE: Oxidized LDL (oxLDL) is involved in the pathogenesis of
      atherosclerosis. Thus, it is important to investigate putative risk factors for
      increased oxLDL. Evidence suggests that, compared to euthyroid individuals, LDL
      cholesterol (LDL-C) levels are lower in individuals with overt hyperthyroidism.
      Whereas oxidization of LDL-C into oxLDL is increased in overt hyper- and
      hypothyroidism, it has not been investigated whether subclinical thyroid
      dysfunction impacts on oxLDL levels in general. We have analysed the association
      between serum thyrotrophin (TSH) levels and oxLDL in a population-based study.
      DESIGN, PATIENTS AND MEASUREMENTS: Of the 4308 individuals enrolled in the Study
      of Health in Pomerania, data from 3519 individuals were analysed (680 missing the
      oxLDL variable). oxLDL was measured by the oxLDL competitive ELISA on a BEP 2000.
      Multivariable linear regression models were performed to assess the association
      between serum TSH and oxLDL levels. RESULTS: TSH was positively associated with
      oxLDL in a curvilinear fashion with increasing serum TSH levels. Subgroup
      analyses revealed a significant association only in the group of individuals >60
      years. Additionally, serum TSH levels were not associated with the ratio of oxLDL
      to LDL (beta = -0.04; 95% CI = -0.08, 0.01; P = 0.084). CONCLUSIONS: We
      demonstrate an association between serum TSH and oxLDL levels especially in the
      range of subclinical thyroid disease. Our study suggests that serum TSH levels
      affect LDL-C production or clearance rather than the LDL-C oxidation processes.

PMID- 21848646
TI  - Neuroendocrinology of parental response to baby-cry.
AB  - This overview attempts to synthesise current understandings of the neuroendocrine
      basis of parenting. The parent-infant bond is central to the human condition,
      contributes to risks for mood and anxiety disorders, and provides the potential
      for resiliency and protection against the development of psychopathology. Animal
      models of parenting provide compelling evidence that biological mechanisms may be
      studied in humans. This has led to brain imaging and endocrine system studies of
      human parents using baby stimuli and concerted psychological and behavioural
      measures. Certain brain circuits and related hormonal systems, including
      subcortical regions for motivation (striatum, amygdala, hypothalamus and
      hippocampus) and cortical regions for social cognition (anterior cingulate,
      insula, medial frontal and orbitofrontal cortices), appear to be involved. These
      brain circuits work with a range of endocrine systems to manage stress and
      motivate appropriate parental caring behaviour with a flexibility appropriate to
      the environment. Work in this field promises to link evolving models of parental
      brain performance with resilience, risk and treatment toward mother-infant mental
      health.

PMID- 21848648
TI  - Expression of oestrogen receptor alpha in the brain of Brandt's voles
      (Lasiopodomys brandtii ): sex differences and variations during ovarian cycles.
AB  - Oestrogen receptor (ER) alpha plays an important role in a variety of cognitive
      and behavioural functions. It has been shown that ERalpha expression in the brain
      is sexually dimorphic and is influenced by circulating oestrogen. In the present
      study, we mapped ERalpha-immunoreactive (-ir) cells in the forebrain of Brandt's
      voles (Lasiopodomys brandtii) to examine differences in ERalpha-ir expression
      between males and females and to reveal variations of ERalpha-ir expression
      during ovarian cycles in females. ERalpha-ir cells were found in many forebrain
      regions, including the lateral septum, bed nucleus of the stria terminalis,
      medial preoptic area (MPOA), anterior, arcuate and ventral medial (VMH) nuclei of
      the hypothalamus, as well as medial (MeA) and anterior cortical nuclei of the
      amygdala. Females had more ERalpha-ir cells in the VMH than males. Females during
      ovarian oestrus, but not di-oestrus or pro-oestrus, also had more ERalpha-ir
      cells in the MPOA than males. Furthermore, females in ovarian di-oestrus or
      oestrus had more ERalpha-ir cells in the MeA than males. Together, these data
      indicate that ERalpha expression in the brain of Brandt's voles is sexually
      dimorphic in specific brain areas. In addition, variations in the levels of
      circulating oestrogen during ovarian cycles can affect ERalpha expression in the
      female brain in a region-specific manner.

PMID- 21848647
TI  - Transient receptor potential channel m4 and m5 in magnocellular cells in rat
      supraoptic and paraventricular nuclei.
AB  - The neurohypophysial hormones, vasopressin (VP) and oxytocin (OT), are
      synthesised by magnocellular cells in the supraoptic nucleus (SON) and the
      paraventricular nucleus (PVN) of the hypothalamus. The release of VP into the
      general circulation from the neurohypophysis increases during hyperosmolality,
      hypotension and hypovolaemia. VP neurones increase hormone release by increasing
      their firing rate as a result of adopting a phasic bursting. Depolarising after
      potentials (DAPs) following a series of action potentials are considered to be
      involved in the generation of the phasic bursts by summating to plateau
      potentials. We recently discovered a fast DAP (fDAP) in addition to the slower
      DAP characterised previously. Almost all VP neurones expressed the fDAP, whereas
      only 16% of OT neurones had this property, which implicates the involvement of
      fDAP in the generation of the firing patterns in VP neurones. Our findings
      obtained from electrophysiological experiments suggested that the ionic current
      underlying the fDAP is mediated by those of two closely-related Ca(2+) -activated
      cation channels: the melastatin-related subfamily of transient receptor potential
      channels, TRPM4 and TRPM5. In the present study, double/triple immunofluorescence
      microscopy and reverse transcriptase-polymerase chain reaction techniques were
      employed to evaluate whether TRPM4 and TRPM5 are specifically located in VP
      neurones. Using specific antibodies against these channels, TRPM5
      immunoreactivity was found almost exclusively in VP neurones, but not in OT
      neurones in both the SON and PVN. The most prominent TRPM5 immunoreactivity was
      in the dendrites of VP neurones. By contrast, most TRPM4 immunoreactivity
      occurred in cell bodies of both VP and OT neurones. TRPM4 and TRPM5 mRNA were
      both found in a cDNA library derived from SON punches. These results indictate
      the possible involvement of TRPM5 in the generation of the fDAP, and these
      channels may play an important role in determining the distinct firing properties
      of VP neurones in the SON.

PMID- 21848650
TI  - Facial asymmetry and clinical manifestations in patients with novel insertion of
      the TCOF1 gene.
AB  - This study explored the role of TCOF1 insertion mutations in Taiwanese patients
      with craniofacial anomalies. Twelve patients with single or multiple,
      asymmetrical congenital craniofacial anomalies were enrolled. Genomic DNA was
      prepared from leukocytes; the coding regions of TCOF1 were analyzed by polymerase
      chain reaction and direct sequencing. Clinical manifestations were correlated to
      the TCOF1 mutation. Six of 12 patients diagnosed with hemifacial microsomia
      exhibited a novel insertion mutation 4127 ins G (frameshift) in exon 24 in the
      TCOF1 gene. All six patients were diagnosed with anomalies on the left side. In
      addition, four of these six patients had hearing impairment; three had other
      major anomalies; and two had developmental delay. The insertion caused a
      frameshift, an early truncation, the loss of two putative nuclear localization
      signals (residues 1404-1420 and 1424-1440), and the loss of coiled coil domain
      (1406-1426) in treacle protein. These findings support the existence of two
      regulators of growth of the mandibular condyles.

PMID- 21848649
TI  - Brain-derived neurotrophic factor-tyrosine kinase B pathway mediates NMDA
      receptor NR2B subunit phosphorylation in the supraoptic nuclei following
      progressive dehydration.
AB  - We studied the effects of water deprivation (WD) on the phosphorylation of
      tyrosine kinase B (TrkB) and NMDA receptor subunits in the supraoptic nucleus
      (SON) of the rat. Laser capture microdissection and quantitative reverse
      transcriptase polymerase chain reaction was used to demonstrate brain-derived
      neurotrophic factor (BDNF) and TrkB gene expression in vasopressin SON neurones.
      Immunohistochemistry confirmed BDNF staining in vasopressin neurones, whereas
      staining for phosphorylated TrkB was increased following WD. Western blot
      analysis of brain punches containing the SON revealed that tyrosine
      phosphorylation of TrkB (pTrkBY(515)), serine phosphorylation of NR1 (pNR1S(866)
      or pNR1) and tyrosine phosphorylation of NR2B subunits (pNR2BY(1472) or pNR2B)
      were significantly increased in WD animals compared to controls. Access to water
      for 2 h reduced pTrkBY(515) content to control levels without affecting pNR1 or
      pNR2B. Four hours of rehydration was needed to reduce pNR1 and pNR2B to control
      levels. To test whether increased phosphorylation of TrkB in the present study is
      mediated by BDNF, a group of animals were instrumented with right SON cannula
      coupled to mini-osmotic pumps filled with vehicle or TrkB-Fc fusion protein,
      which prevents BDNF binding to TrkB. In the left SON contralateral to the
      cannula, TrkB phosphorylation was significantly enhanced following WD. Separate
      analysis of the right SON, which received TrkB-Fc, showed that the TrkB receptor
      phosphorylation following WD was significantly attenuated. Although increased
      pNR1S(866) following WD was not affected by local infusion of TrkB-Fc,
      pNR2BY(1472) was significantly reduced. Co-immunoprecipitation revealed an
      increased physical interaction between Fyn kinase and NR2B and TrkB in the SON
      following WD. Thus, activation of TrkB in the SON following WD may affect
      cellular excitability through the phosphorylation of NR2B subunits.

PMID- 21848651
TI  - The significance of glutathione for photoprotection at contrasting temperatures
      in the alpine plant species Soldanella alpina and Ranunculus glacialis.
AB  - The significance of total glutathione content was investigated in two alpine
      plant species with highly differing antioxidative scavenging capacity. Leaves of
      Soldanella alpina and Ranunculus glacialis incubated for 48 h in the presence of
      buthionine-sulfoximine had 50% lower glutathione contents when compared with
      leaves incubated in water. The low leaf glutathione content was not compensated
      for by activation of other components involved in antioxidative protection or
      electron consumption. However, leaves with normal but not with low glutathione
      content increased their ascorbate content during high light (HL) treatment (S.
      alpina) or catalase activity at low temperature (LT) (R. glacialis), suggesting
      that the mere decline of the leaf glutathione content does not act as a signal to
      ameliorate antioxidative protection by alternative mechanisms. CO(2)-saturated
      oxygen evolution was not affected in glutathione-depleted leaves at various
      temperatures, except at 35 degrees C, thereby increasing the high temperature
      (HT) sensitivity of both alpine species. Leaves with low and normal glutathione
      content were similarly resistant to photoinhibition and photodamage during HL
      treatment at ambient temperature in the presence and absence of paraquat or at
      LT. However, HL- and HT-induced photoinhibition increased in leaves with low
      compared to leaves with normal glutathione content, mainly because the recovery
      after heat inactivation was retarded in glutathione-depleted leaves. Differences
      in the response of photosystem II (PSII) activity and CO(2)-saturated
      photosynthesis suggest that PSII is not the primary target during HL inactivation
      at HT. The results are discussed with respect to the role of antioxidative
      protection as a safety valve for temperature extremes to which plants are not
      acclimated.

PMID- 21848652
TI  - PPIase activities and interaction partners of FK506-binding proteins in the wheat
      thylakoid.
AB  - FK506-binding proteins (FKBPs) and cyclophilins, collectively called
      immunophilins, conserve peptidyl-prolyl cis/trans isomerase (PPIase) active
      sites, although many lack PPIase activity. The chloroplast thylakoid contains a
      large proportion of the plant immunophilin family, but their functions within
      this compartment are unclear. Some lumenal immunophilins are important for
      assembly of photosynthetic complexes, implicating them in the maintenance and
      turnover of the photosynthetic apparatus during acclimation processes. In this
      investigation into the functions of three FKBPs localized to the thylakoid of
      Triticum aestivum (wheat), we present the first evidence of PPIase activity in
      the thylakoid of a cereal plant, and also show that PPIase activity is not
      conserved in all lumenal FKBPs. Using yeast two-hybrid analysis we found that the
      PPIase-active FKBP13 interacts with the globular domain of the wheat Rieske
      protein, with potential impact on photosynthetic electron transfer. Specific
      interaction partners for PPIase-deficient FKBP16-1 and FKBP16-3 link these
      isoforms to photosystem assembly.

PMID- 21848653
TI  - Factors controlling plasticity of leaf morphology in Robinia pseudoacacia: III.
      biophysical constraints on leaf expansion under long-term water stress.
AB  - In this article, we measured the relative growth rate (RGR) of leaves of Robinia
      pseudoacacia seedlings under well-watered and water-stressed conditions (mid-day
      Psi(w) = leaf water potential estimated with a pressure bomb of -0.48 and -0.98
      MPa, respectively). Pressure-volume (PV) curves were done on growing leaves at
      25, 50 and 95% of the mature size (growth stage) in order to compute solute
      potential (Psi) and turgor pressure (Psi(P) ) as a function of Psi(w) . The PV
      curves and diurnal measurements of Psi(w) and RGR allowed us to evaluate the
      parameters (cell wall extensibility m and growth turgor threshold Y) of the
      Lockhart equation, RGR = m(Psi(P)-Y), at each growth stage. Our data showed that
      m and Y did change with leaf age, but the changes were slow enough to evaluate m
      and Y on any given day. We believe this is the first study to provide evidence
      that the Lockhart equation adequately quantifies leaf growth of trees over a
      range of time domains. The value of m linearly declined and Y linearly increased
      with growth stage. Also, mild drought stress caused a decline in m and increase
      in Y relative to controls. Although water stress caused an osmotic adjustment
      which, in turn, increased Psi(P) in stressed plants relative to controls, the RGR
      and final leaf sizes were reduced in water-stressed plants because of the impact
      of water stress on decreased m and increased Y.

PMID- 21848654
TI  - Glucose and ethylene signalling pathways converge to regulate trans
      differentiation of epidermal transfer cells in Vicia narbonensis cotyledons.
AB  - Transfer cells are specialized transport cells containing invaginated wall
      ingrowths that provide an amplified plasma membrane surface area with high
      densities of transporter proteins. They trans-differentiate from differentiated
      cells at sites where enhanced rates of nutrient transport occur across
      apo/symplasmic boundaries. Despite their physiological importance, the signal(s)
      and signalling cascades responsible for initiating their trans-differentiation
      are poorly understood. In culture, adaxial epidermal cells of Vicia narbonensis
      cotyledons were induced to trans-differentiate to a transfer cell morphology.
      Manipulating their intracellular glucose concentrations by transgenic knock-down
      of ADP-glucose pyrophosphorylase expression and/or culture on a high-glucose
      medium demonstrated that glucose functioned as a negative regulator of wall
      ingrowth induction. In contrast, glucose had no detectable effect on wall
      ingrowth morphology. The effect on wall ingrowth induction of culture on media
      containing glucose analogues suggested that glucose acts through a hexokinase
      dependent signalling pathway. Elevation of an epidermal cell-specific ethylene
      signal alone, or in combination with glucose analogues, countered the negative
      effect of glucose on wall ingrowth induction. Glucose modulated the amplitude of
      ethylene-stimulated wall ingrowth induction by down-regulating the expression of
      ethylene biosynthetic genes and an ethylene insensitive 3 (EIN3)-like gene (EIL)
      encoding a key transcription factor in the ethylene signalling cascade. A model
      is presented describing the interaction between glucose and ethylene signalling
      pathways regulating the induction of wall ingrowth formation in adaxial epidermal
      cells.

PMID- 21848655
TI  - Functional HAK/KUP/KT-like potassium transporter encoded by chlorella viruses.
AB  - Chlorella viruses are a source of interesting membrane transport proteins. Here
      we examine a putative K(+)  transporter encoded by virus FR483 and related
      chlorella viruses. The protein shares sequence and structural features with
      HAK/KUP/KT-like K(+)  transporters from plants, bacteria and fungi. Yeast
      complementation assays and Rb(+)  uptake experiments show that the viral protein,
      termed HAKCV (high-affinity K(+)  transporter of chlorella virus), is functional,
      with transport characteristics that are similar to those of known K(+) 
      transporters. Expression studies revealed that the protein is expressed as an
      early gene during viral replication, and proteomics data indicate that it is not
      packaged in the virion. The function of HAKCV is unclear, but the data refute the
      hypothesis that the transporter acts as a substitute for viral-encoded K(+) 
      channels during virus infection.

PMID- 21848656
TI  - Cyclic electron flow around photosystem I via chloroplast NAD(P)H dehydrogenase
      (NDH) complex performs a significant physiological role during photosynthesis and
      plant growth at low temperature in rice.
AB  - The role of NAD(P)H dehydrogenase (NDH)-dependent cyclic electron flow around
      photosystem I in photosynthetic regulation and plant growth at several
      temperatures was examined in rice (Oryza sativa) that is defective in
      CHLORORESPIRATORY REDUCTION 6 (CRR6), which is required for accumulation of sub
      complex A of the chloroplast NDH complex (crr6). NdhK was not detected by Western
      blot analysis in crr6 mutants, resulting in lack of a transient post-illumination
      increase in chlorophyll fluorescence, and confirming that crr6 mutants lack NDH
      activity. When plants were grown at 28 or 35 degrees C, all examined
      photosynthetic parameters, including the CO(2) assimilation rate and the electron
      transport rate around photosystems I and II, at each growth temperature at light
      intensities above growth light (i.e. 800 MUmol photons m(-2) sec(-1)), were
      similar between crr6 mutants and control plants. However, when plants were grown
      at 20 degrees C, all the examined photosynthetic parameters were significantly
      lower in crr6 mutants than control plants, and this effect on photosynthesis
      caused a corresponding reduction in plant biomass. The F(v)/F(m) ratio was only
      slightly lower in crr6 mutants than in control plants after short-term strong
      light treatment at 20 degrees C. However, after long-term acclimation to the low
      temperature, impairment of cyclic electron flow suppressed non-photochemical
      quenching and promoted reduction of the plastoquinone pool in crr6 mutants. Taken
      together, our experiments show that NDH-dependent cyclic electron flow plays a
      significant physiological role in rice during photosynthesis and plant growth at
      low temperature.

PMID- 21848657
TI  - Hyperforin promotes mitochondrial function and development of oligodendrocytes.
AB  - St. John's wort has been found to be an effective and safe herbal treatment for
      depression in several clinical trials. However, the underlying mechanism of its
      therapeutic effects is unclear. Recent studies show that the loss and malfunction
      of oligodendrocytes are closely related to the neuropathological changes in
      depression, which can be reversed by antidepressant treatment. In this study, we
      evaluated the effects of hyperforin, a major active component of St. John's wort,
      on the proliferation, development and mitochondrial function of oligodendrocytes.
      The study results revealed that hyperforin promotes maturation of
      oligodendrocytes and increases mitochondrial function without affecting
      proliferation of an oligodendrocyte progenitor cell line and neural
      stem/progenitor cells. Hyperforin also prevented mitochondrial toxin-induced
      cytotoxicity in an oligodendrocyte progenitor cell line. These findings suggest
      that hyperforin may stimulate the development and function of oligodendrocytes,
      which could be a mechanism of its effect in depression. Future in vitro and in
      vivo studies are required to further characterize the mechanisms of hyperforin.

PMID- 21848658
TI  - Quality control parameters on a large dataset of regionally dissected human
      control brains for whole genome expression studies.
AB  - We are building an open-access database of regional human brain expression
      designed to allow the genome-wide assessment of genetic variability on
      expression. Array and RNA sequencing technologies make assessment of genome-wide
      expression possible. Human brain tissue is a challenging source for this work
      because it can only be obtained several and variable hours post-mortem and after
      varying agonal states. These variables alter RNA integrity in a complex manner.
      In this report, we assess the effect of post-mortem delay, agonal state and age
      on gene expression, and the utility of pH and RNA integrity number as predictors
      of gene expression as measured on 1266 Affymetrix Exon Arrays. We assessed the
      accuracy of the array data using QuantiGene, as an independent non-PCR-based
      method. These quality control parameters will allow database users to assess data
      accuracy. We report that within the parameters of this study post-mortem delay,
      agonal state and age have little impact on array quality, array data are robust
      to variable RNA integrity, and brain pH has only a small effect on array
      performance. QuantiGene gave very similar expression profiles as array data. This
      study is the first step in our initiative to make human, regional brain
      expression freely available.

PMID- 21848659
TI  - A kinetic model linking protein conformational motions, interflavin electron
      transfer and electron flux through a dual-flavin enzyme-simulating the reductase
      activity of the endothelial and neuronal nitric oxide synthase flavoprotein
      domains.
AB  - NADPH-dependent dual-flavin enzymes provide electrons in many redox reactions,
      although the mechanism responsible for regulating their electron flux remains
      unclear. We recently proposed a four-state kinetic model that links the electron
      flux through a dual-flavin enzyme to its rates of interflavin electron transfer
      and FMN domain conformational motion [Stuehr DJ et al. (2009) FEBS J276, 3959
      3974]. In the present study, we ran computer simulations of the kinetic model to
      determine whether it could fit the experimentally-determined, pre-steady-state
      and steady-state traces of electron flux through the neuronal and endothelial NO
      synthase flavoproteins (reductase domains of neuronal nitric oxide synthase and
      endothelial nitric oxide synthase, respectively) to cytochrome c. We found that
      the kinetic model accurately fitted the experimental data. The simulations gave
      estimates for the ensemble rates of interflavin electron transfer and FMN domain
      conformational motion in the reductase domains of neuronal nitric oxide synthase
      and endothelial nitric oxide synthase, provided the minimum rate boundary values,
      and predicted the concentrations of the four enzyme species that cycle during
      catalysis. The findings of the present study suggest that the rates of
      interflavin electron transfer and FMN domain conformational motion are
      counterbalanced such that both processes may limit electron flux through the
      enzymes. Such counterbalancing would allow a robust electron flux at the same
      time as keeping the rates of interflavin electron transfer and FMN domain
      conformational motion set at relatively slow levels.

PMID- 21848660
TI  - Coagulation and fibrinolytic disturbances are related to carotid intima thickness
      and arterial blood pressure in Turner syndrome.
AB  - OBJECTIVE: Turner syndrome (TS) is characterized by growth retardation,
      hypogonadism and a high risk of cardiovascular complications and atherosclerosis;
      case reports suggest that thrombo-embolic complications may be present. DESIGN:
      Cross-sectional study. PATIENTS: Sixty women with TS. MEASUREMENTS: We
      characterized the activities of the haemostatic system, elucidated by the
      assessment of a panel of clotting factors and thrombosis risk factors and related
      these findings to carotid intima thickness (CIMT) and blood pressure. RESULTS:
      Most (81%) received hormone replacement therapy. The medians of all measured
      factors and inflammatory parameters were not different from normative data, but
      many cases displayed values of C-reactive protein (CRP) (40%), fibrinogen (15%),
      fibrin D-dimer (15%), factor VIII (25%), von Willebrand factor (vWF) (15%),
      cholesterol and liver parameters that were greater than normative limits. CRP,
      fibrinogen, vWF, factor VIII and liver parameters were highly and positively
      correlated. Haemostatic variables were positively related to both CIMT and blood
      pressure. The Factor V Leiden G1691A gene polymorphism heterozygosity was
      detected in 12.5%. CONCLUSION: We describe a significant proportion of individual
      TS females having high levels of vWF, factor VIII, fibrinogen and CRP (15-40%)
      and an increased frequency of the Leiden mutation, with important associations
      with CIMT and blood pressure, suggesting that a subset of TS may have an
      unfavourable haemostatic balance, which may contribute to the increased risk of
      premature ischaemic heart disease and possibly increase the risk of deep venous
      and portal vein thrombosis.

PMID- 21848661
TI  - A method of accelerating transport simulation when groundwater pumping is
      simulated.
AB  - In solving groundwater transport problems with numerical models, the computation
      time (CPU processing time) of transport simulation is approximately inversely
      proportional to the transport time-step size. Therefore, large time-step sizes
      are favorable for achieving short computation time. However, transport time-step
      size must be sufficiently small to avoid numerical instability if an explicit
      scheme is used (and to guarantee enough model accuracy if an implicit scheme is
      used). For a transport model involving groundwater pumping, a small transport
      time-step size is often required due to the high groundwater velocities near the
      pumping well. Small grid spacing often specified near the pumping well also
      limits the time-step size. This paper presents a method to increase transport
      time-step size in a transport model when groundwater pumping is simulated. The
      key to this approach is to numerically decrease the groundwater seepage
      velocities in grid cells near the pumping well by increasing the effective
      porosity so that the transport time-step size can be increased without violating
      stability constraints. Numerical tests reveal that by using the proposed method,
      the computation time of transport simulation can be reduced significantly, while
      the transport simulation results change very little.

PMID- 21848662
TI  - Shape factors of cylindrical piezometers in uniform soil.
AB  - This article presents the analytical solution of Laplace equation for the steady
      flow around open-ended cylindrical piezometers located in an infinite, isotropic,
      and incompressible saturated soil. Shape factors are obtained for piezometers
      with varying length-to-diameter ratios. Comparisons are made with published
      factors obtained by means of approximate analytical solutions, numerical
      approaches, and measurements in electric analog models. It is shown that some
      expressions that are currently used in practice are inadequate and should be
      abandoned.

PMID- 21848663
TI  - Transcriptional signatures of full-spectrum and non-UVB-spectrum solar
      irradiation in human skin.

PMID- 21848664
TI  - Epigenetics and assisted reproductive technology.
AB  - During gametogenesis, the female and male germ cells undergo a process whereby
      imprinting marks are erased from the genome. During the later stages of germ-cell
      development, the methylation marks of the female and male germ lines are re
      established. A second phase of demethylation of the genome occurs at the time of
      fertilization, and during development of the early embryo. Assisted reproductive
      technology involves several steps that subject the gametes and early developing
      embryos to environmental stress, and this is the primary reason for an increased
      interest in the putative link between these techniques and imprinting disorders.
      Although animal studies support a link between assisted reproductive techniques
      (ARTs) and imprinting disorders, via altered methylation patterns, data in humans
      are inconsistent. Here we provide an overview of the field of epigenetics in
      relation to ARTs.

PMID- 21848665
TI  - Synthesis and in vitro Evaluation of Novel Indole-Based Sigma Receptors Ligands.
AB  - To investigate the molecular features involved in sigma (sigma) receptors
      binding, a series of compounds based on indole scaffolds were synthesized and
      their chemical structures were confirmed by (1) H-NMR, IR, and elemental
      analysis. Their affinity toward sigma(1)  and sigma(2)  receptor subtypes was
      evaluated. 1-{[4-(2-phenylethyl)piperazin-1-yl]methyl}-3-methyl-1H-indole 3b had
      a high affinity to sigma(1)  receptors, while three compounds, 1-{3-[4
      (substitutedphenyl)piperazin-1-yl]propyl}-1H-indole derivatives 4a-c had shown
      high affinity and selectivity for sigma(2)  receptors. Cytotoxicity of the
      compounds was demonstrated on cancer cell lines from liver (HUH7), breast (MCF7),
      and colon (HCT-116) cancer cell lines. Compound 1c (3-{[4-(3,4
      dichlorobenzyl)piperazin-1-yl]methyl}-1H-indole) showed significant cell growth
      inhibitory activity on the selected cancer cell lines.

PMID- 21848666
TI  - Castleman's disease: a rare presacral tumour.

PMID- 21848667
TI  - Faecal impaction: in-hospital complications and their predictors in a
      retrospective study on 130 patients.
AB  - AIM: Faecal impaction may be a medical emergency. The frequency of complications
      of this condition and their predictors are not known. We determined the clinical
      presentation, the in-hospital complications and their predictors in 130 patients
      diagnosed with faecal impaction. METHOD: This was a retrospective study of the
      medical records of 130 patients who presented with faecal impaction to a tertiary
      care center in Beirut, Lebanon, between 1992 and 2009. The clinical outcome and
      complications were reviewed. The association between in-hospital complications
      and other variables was determined. RESULTS: The mean age of the patients was
      67.1 years. Ninety-eight (75.3%) patients had at least one of the following:
      heart disease (36.3%), neurological disease (28.8%) or diabetes (22.6%), and
      26.7% were bedridden. The site of impaction was the rectum in 66.4%. The patients
      were treated by manual disimpaction (34.5%), enema (89.1%) or oral laxatives
      (84.0%). A delay in treatment of more than 6 h occurred in 70 (53.8%) patients.
      In-hospital complications occurred in 34 (24.6%) patients, the most common of
      which were infectious (16 cases), systemic inflammatory response syndrome (16
      cases), cardiopulmonary (14 cases) and death (one patient). Time to the start of
      treatment was longer in patients who developed complications compared with those
      who did not (10.1 h vs 7.1 h; P = 0.02). Patients > 80 years of age, or patients
      with heart or neurological disease were at a higher risk of developing
      complications (P = 0.03, P = 0.03 and P = 0.02, respectively). CONCLUSION:
      Treatment delay, increasing age and the presence of heart or neurological disease
      seem to be predictors of in-hospital complications in patients with faecal
      impaction.

PMID- 21848668
TI  - Unpredictable rotational responses to L-dopa in the rat model of Parkinson's
      disease: the role of L-dopa pharmacokinetics and striatal dopamine depletion.
AB  - L-dopa is still the gold standard in the symptomatic treatment of Parkinson's
      disease (PD), and thus, it is the most commonly used drug in the non-clinical
      assessment of new drug therapies to PD, including those intended to improve the
      effect of L-dopa. In unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat model
      of PD, the results from L-dopa-induced rotation tests are often unpredictable.
      While repeated administration of L-dopa improves the rotation, the exact
      mechanisms underlying the extensive variability in rotation responses between
      rats and testing times are unclear. In the present study, we aimed to assess
      whether the route of administration (oral or intraperitoneal) or the form of L
      dopa (base or methyl ester) is associated with the extensive variation in
      rotation responses to L-dopa in 6-OHDA rats. We also wanted to examine the
      dependence between L-dopa (base or methyl ester)-induced rotational behaviour and
      the extent of dopamine and dopa decarboxylase enzyme loss in the lesioned
      striatum. It was found that variation in plasma levels of L-dopa as well as the
      administration route explains a part of the variability in rotation. There were
      small but significant differences in striatal dopamine depletion (indicative of
      degree of lesion) between the groups, which may partially account for the various
      patterns in L-dopa-induced rotational behaviour. While apomorphine-induced
      rotation test is a useful tool for primary screening of the success of 6-OHDA
      lesion, it is not useful at predicting the rotational performance of 6-OHDA rats
      to L-dopa. The exact mechanisms and causes of the variability in the rotation
      responses to L-dopa in 6-OHDA rats still remain to be clarified. 

PMID- 21848669
TI  - Homology-modelled structure of the betaB2B3-crystallin heterodimer studied by ion
      mobility and radical probe MS.
AB  - Ion mobility MS was employed to study the structure of the betaB2B3-crystallin
      heterodimer following its detection by ESI-TOF MS. The results demonstrate that
      the heterodimer has a similar cross-section (3 165 A(2)) and structure to the
      betaB2B2-crystallin homodimer. Several homology-modelled structures for the
      betaB2B3 heterodimer were constructed and assessed in terms of their calculated
      collision cross-sections and whether the solvent accessibilities of reactive
      amino acid side chains throughout the betaB3 subunit are in accord with measured
      oxidation levels in radical probe MS protein footprinting experiments. The
      betaB2B3 heterodimer AD model provides the best representation of the
      heterodimer's structure overall following a consideration of both the ion
      mobility and radical probe MS data.

PMID- 21848670
TI  - Body fat mass is a predictor of risk of osteoporotic fractures in women but not
      in men: a prospective population study.
AB  - OBJECTIVES: Obesity has generally been associated with higher bone density and
      lower fracture risk. However, weight-related indices of obesity may be related
      differently to health end-points, compared with fat-related indices (such as body
      fat distribution and fat mass), as they may capture different dimensions of
      obesity and the associated biological effects. The aim of this study was to
      examine the association between percentage body fat (%BF) and prospective risk of
      fracture. METHODS: The European Prospective Investigation into Cancer (EPIC) in
      Norfolk was a population-based prospective study. A total of 14 789 participants
      (6470 men, aged 42-82 years at baseline) were included. The main outcome measures
      were quantitative ultrasound of the heel and incident hip and any osteoporotic
      fractures. RESULTS: A total of 556 participants suffered a fracture (184 hip
      fractures) during 8.7 +/- 0.8 years of follow-up. Risk of hip fracture decreased
      linearly with increasing %BF amongst women but not men. After adjustment for age,
      history of fracture, height, smoking, alcohol intake and heel broadband
      ultrasound attenuation (BUA), the hazard ratio (95% CI) for a 10% higher %BF on
      risk of hip fracture was 0.56 (0.39-0.79) in women and 0.92 (0.39-2.21) in men.
      The effect size in women was approximately equivalent to a difference of 5 years
      in age or 1 standard deviation (17 dB MHz(-1) ) increased BUA. A nonlinear
      negative association was also observed between %BF and risk of 'any type of
      fracture' amongst women but not men. CONCLUSIONS: The %BF appears to predict hip
      fracture risk in women with an effect size comparable to that of bone density as
      measured by heel ultrasound. This effect was not observed in men. Understanding
      the differences in relationships between different indices of obesity as well as
      sex differences may help to elucidate the metabolic and other underlying
      mechanisms involved in bone health and fracture risk.

PMID- 21848671
TI  - Role of HoxE subunit in Synechocystis PCC6803 hydrogenase.
AB  - Cyanobacterial NAD(P)(+)-reducing reversible hydrogenases comprise five subunits.
      Four of them (HoxF, HoxU, HoxY, and HoxH) are also found in the well-described
      related enzyme from Ralstonia eutropha. The fifth one (HoxE) is not encoded in
      the R. eutropha genome, but shares homology with the N-terminal part of R.
      eutropha HoxF. However, in cyanobacteria, HoxE contains a 2Fe-2S cluster-binding
      motif that is not found in the related R. eutropha sequence. In order to obtain
      some insights into the role of HoxE in cyanobacteria, we deleted this subunit in
      Synechocystis PCC6803. Three types of interaction of the cyanobacterial
      hydrogenase with pyridine nucleotides were tested: (a) reductive activation of
      the NiFe site, for which NADPH was found to be more efficient than NADH; (b) H(2)
      production, for which NADH appeared to be a more efficient electron donor than
      NADPH; and (c) H(2) oxidation, for which NAD(+) was a much better electron
      acceptor than NADP(+). Upon hoxE deletion, the Synechocystis hydrogenase active
      site remained functional with artificial electron donors or acceptors, but the
      enzyme became unable to catalyze H(2) production or uptake with NADH/NAD(+).
      However, activation of the electron transfer-independent H/D exchange reaction by
      NADPH was still observed in the absence of HoxE, whereas activation of this
      reaction by NADH was lost. These data suggest different mechanisms for diaphorase
      mediated electron donation and catalytic site activation in cyanobacterial
      hydrogenase.

PMID- 21848672
TI  - Genome walking in eukaryotes.
AB  - Genome walking is a molecular procedure for the direct identification of
      nucleotide sequences from purified genomes. The only requirement is the
      availability of a known nucleotide sequence from which to start. Several genome
      walking methods have been developed in the last 20 years, with continuous
      improvements added to the first basic strategies, including the recent coupling
      with next generation sequencing technologies. This review focuses on the use of
      genome walking strategies in several aspects of the study of eukaryotic genomes.
      In a first part, the analysis of the numerous strategies available is reported.
      The technical aspects involved in genome walking are particularly intriguing,
      also because they represent the synthesis of the talent, the fantasy and the
      intelligence of several scientists. Applications in which genome walking can be
      employed are systematically examined in the second part of the review, showing
      the large potentiality of this technique, including not only the simple
      identification of nucleotide sequences but also the analysis of large collections
      of mutants obtained from the insertion of DNA of viral origin, transposons and
      transfer DNA (T-DNA) constructs. The enormous amount of data obtained indicates
      that genome walking, with its large range of applicability, multiplicity of
      strategies and recent developments, will continue to have much to offer for the
      rapid identification of unknown sequences in several fields of genomic research.

PMID- 21848673
TI  - Increased expression of nonmuscle myosin IIs is associated with 3MC-induced mouse
      tumor.
AB  - Administration of the chemical carcinogen, 3-methylcholanthrene (3MC), in the
      hind leg induces the progressive formation of tumors in mice within 110 days.
      Previous reports suggest that transformation of muscle cells to atypical cells is
      one of the causes of tumor formation. Molecular events that lead to
      transformation of normal cells to atypical cells are not well understood. Here,
      we investigate the effect of 3MC on the expression of nonmuscle myosin IIs (NM
      IIs) which are known to be involved in cell migration, division and adhesion.
      Mass spectroscopy analysis reveals that tumor tissue contains 64.5% NM II-A, 34%
      II-B and only 1.5% II-C of total NM IIs, whereas these three isoforms of NM IIs
      are undetectable by mass spectroscopy in normal tissue associated with the tumor
      (NTAT) from the hind leg. Quantification of heavy chain mRNAs of NM II suggests
      that tumor tissue contains 25.7-fold and 19.03-fold more of NM II-A and II-B,
      respectively, compared with NTAT. Unlike NM II-B, which is detected only after
      tumor formation, II-A is detectable as early as day 7 after a second dose of 3MC.
      Immunofluorescence confocal microscopy reveals that fibroblast cells which are
      sparsely distributed in normal tissue are densely populated but of atypical shape
      in the tumor. These findings suggest that transformation of fibroblasts or non
      fibroblast cells to atypical, cancerous cells is associated with increased levels
      of NM II-A and NM II-B expression in the 3MC-induced tumor mouse model. 3MC
      induced transformation is further demonstrated in C2C12 myotubes.

PMID- 21848674
TI  - Cytologic, histologic, and immunohistochemical features of lingual liposarcoma in
      a dog.
AB  - A 9-year-old female spayed mixed-breed dog was presented to the referring
      veterinarian with a history of decreased appetite and difficulty with prehension
      and swallowing because of a firm oval mass in the tongue. On cytologic evaluation
      of a fine-needle aspirate of the mass there were numerous round to polygonal
      cells organized individually or in loose clusters with rare branching
      capillaries. The cells had eosinophilic granular cytoplasm, round to oval nuclei,
      and occasionally indistinct borders. The cytologic diagnosis was granular cell
      tumor (GCT) of the tongue. Impression smears of a biopsy sample of the lingual
      mass contained similar eosinophilic granular cells with variable numbers of clear
      vacuoles in the background, numerous perivascular arrangements, and occasional
      lipoblasts, suggestive of liposarcoma. On histologic examination the tumor was
      composed of numerous lipocytes with rare foci of round eosinophilic granular
      cells without evidence of vacuolation; occasionally, atypical mitotic figures
      were seen. Immunohistochemically, the cells were uniformly negative for periodic
      acid-Schiff and did not express smooth muscle actin, desmin, or cytokeratin but
      were immunoreactive for vimentin and S100. A diagnosis of well-differentiated
      liposarcoma was made on the basis of morphologic and immunohistochemical results.
      Eosinophilic granular cells may be a component of well-differentiated liposarcoma
      and are not limited to GCT. Liposarcoma should be considered in the differential
      diagnoses of lingual tumors in the dog when cytological evaluation reveals
      eosinophilic granular cells consistent with GCT.

PMID- 21848675
TI  - What is your diagnosis? Fine-needle aspirate of ulcerative skin lesions in a dog.

PMID- 21848676
TI  - Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs.
AB  - BACKGROUND: C-reactive protein (CRP) is a sensitive marker for inflammation in
      people and dogs. In people, an association between CRP concentration and
      atherosclerosis has been reported. Atherosclerosis is rare in dogs, but the
      Miniature Schnauzer breed may be at increased risk for developing this vascular
      disease. It is not known if CRP concentrations in Miniature Schnauzer dogs differ
      from those in other dog breeds. OBJECTIVES: Our objectives were to validate an
      automated human CRP assay for measuring CRP in dogs and compare CRP
      concentrations in healthy Miniature Schnauzer dogs with those in non-Miniature
      Schnauzer breeds. METHODS: Sera from 37 non-Miniature Schnauzer dogs with
      inflammatory disease were pooled and used to validate a human CRP
      immunoturbidimetric assay for measuring canine CRP. Blood was collected from 20
      healthy Miniature Schnauzer dogs and 41 healthy dogs of other breeds. Median
      serum CRP concentration of healthy Miniature Schnauzer dogs was compared with
      that of healthy non-Miniature Schnauzer dogs. RESULTS: The human CRP assay
      measured CRP reliably with linearity between 0 and 20 mg/L. CRP concentration for
      healthy Miniature Schnauzer dogs (median 4.0 mg/L, minimum-maximum 0-18.2 mg/L)
      was significantly higher than for the healthy non-Miniature Schnauzer dogs
      (median 0.1 mg/L, minimum-maximum 0-10.7 mg/L); 17 of the 20 Miniature Schnauzer
      dogs had values that overlapped with those of the non-Miniature Schnauzer dogs.
      CONCLUSIONS: Median CRP concentration of Miniature Schnauzer dogs was slightly
      higher than that of other breeds of dogs. A relationship between higher CRP
      concentration in Miniature Schnauzer dogs and idiopathic hyperlipidemia,
      pancreatitis, and possible increased risk for atherosclerosis remains to be
      determined.

PMID- 21848677
TI  - Dramatic changes of a DWI lesion in a patient with acute ischemic stroke treated
      with IV t-PA.
AB  - A diffusion-weighted imaging (DWI) lesion changed dramatically in a hyperacute
      stroke case treated with intravenous tissue-plasminogen activator (IV t-PA). The
      initial hyperintense lesion on DWI disappeared completely immediately after IV t
      PA treatment without improvement of neurological symptoms. However, the lesion
      reappeared 24 hours later. Successful thrombolysis can resolve DWI lesions but
      does not always improve the neurological symptoms.

PMID- 21848678
TI  - Quantification of target population for ultrasound enhanced thrombolysis in acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Insonation of the occluded target vessel
      (sonothrombolysis) has been reported to increase the effect of intravenous
      thrombolysis in ischemic stroke. Its use has predominantly been described in
      middle cerebral artery (MCA) occlusions. Sufficient insonation conditions are a
      mandatory precondition. The impact of these limitations on eligibility rates for
      sonothrombolysis has not been reported so far. METHODS: Consecutive patients
      treated with rt-PA and examined by either CT- or MR-angiogram before treatment
      and by transcranial color-coded duplex sonography (TCCS) during inhospital stay
      were identified retrospectively at three hospitals from ongoing data registries.
      RESULTS: One-hundred and seventy-nine patients (age [years], median [IQR] = 75
      [65-83]; 42% female; NIH Stroke Scale [NIHSS], median [IQR] = 10 [6-17]) were
      analyzed. MCA occlusions were detected in 39% of patients (N = 69) with 48 (27%)
      occlusions in the proximal M1-segment and 21 (12%) in a distal M2-segment.
      Arterial occlusions others than MCA were seen in an additional 9% (N = 16). TCCS
      (without contrast agent) revealed sufficient bone windows in 70% of patients with
      MCA occlusions (N = 48) corresponding to 27% of all patients treated with
      thrombolysis. CONCLUSION: Conventional sonothrombolysis is restricted to a
      minority of stroke patients suitable for intravenous thrombolysis. Extending the
      applicability by utilization of ultrasound contrast agents and targeting non-MCA
      occlusions warrants further evaluation.

PMID- 21848679
TI  - The fornix sign: a potential sign for Alzheimer's disease based on diffusion
      tensor imaging.
AB  - BACKGROUND: We investigated a simple imaging sign for Alzheimer's disease (AD),
      using diffusion tensor imaging (DTI). We hypothesized that a reduction in
      fractional anisotropy (FA) in the fornix could be utilized as an imaging sign.
      METHODS: Twenty-three patients with AD, 24 patients with amnestic mild cognitive
      impairment (aMCI), and 25 control participants (NC) underwent DTI at baseline and
      1 year later. The diagnosis was reevaluated 1 year and 3 years after the initial
      scan. A color-scaled FA map was used to visually identify the FA reduction
      ("fornix sign"). We investigated whether the fornix sign could separate AD from
      NC, and could predict progression from aMCI to AD or NC to aMCI. We also
      quantified FA of the fornix to validate the fornix sign. RESULTS: The fornix sign
      was identical to the lack of any voxels with an FA > .52 within the fornix. The
      fornix sign differentiated AD from NC with specificity of 1.0 and sensitivity of
      .56. It predicted conversion from NC to aMCI with specificity of 1.0 and
      sensitivity of .67, and from aMCI to AD with specificity of .94 and sensitivity
      of .83. CONCLUSION: The fornix sign is a promising predictive imaging sign of AD.

PMID- 21848680
TI  - Response to immunotherapy in CLIPPERS: clinical, MRI, and MRS follow-up.
AB  - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
      to steroids (CLIPPERS) is a recently defined inflammatory central nervous system
      disorder responsive to steroids with characteristic magnetic resonance imaging
      (MRI) features. We report a 69-year-old man presenting with gait ataxia with the
      characteristic MRI features of CLIPPERS and describe the clinical, MRI, and
      magnetic resonance spectroscopy (MRS) follow-up after treatment with
      glucocorticosteroids. Brain and spine MRI showed punctate enhancement peppering
      the brainstem, cerebellar peduncles, and upper cervical cord. In MRS, the ratio
      of N-acetyl aspartate to creatine (NAA/Cr) was significantly decreased in the
      pons and both thalami. An extensive evaluation found no alternative diagnoses.
      Treatment with steroids led to rapid clinical improvement. Repeat MRI and MRS
      showed complete resolution of gadolinium-enhancing lesions and recovery of NAA/Cr
      levels in the pons and thalami. After 1 month of tapering oral steroids, weekly
      oral methotrexate was started and the patient has remained stable for the past 6
      months.

PMID- 21848681
TI  - Endovascular treatment of cerebral aneurysms at a low-volume community hospital
      practice: management strategies, complications, and outcomes.
AB  - BACKGROUND AND PURPOSE: Our institution serves a population of 160,000 and
      performed 14.4 endovascular cerebral aneurysm interventions annually, averaged
      over a 5-year period. The purpose of this study was to examine the safety and
      efficacy of endovascular treatment of cerebral aneurysms at a lowvolume center.
      METHODS: Retrospective cohort analysis of 56 patients harboring 64 aneurysms
      requiring 72 procedures over 62 months. Aneurysm morphology, procedure-related
      adverse events and clinical outcomes were analyzed. RESULTS: Twenty-two ruptured
      (34.4%) and 42 unruptured (65.6%) aneurysms were treated in 12 males (mean age
      61.1 years), 44 females (mean age 61.8 years). The procedure-related morbidity
      and mortality was 6.9% (5 of 72) and 1.3% (1 of 72 procedures), respectively.
      Modified Rankin Scale score was 0 or 1 in 87.9% of all discharges (61.9% in the
      ruptured group, 100% in the unruptured group). This score was between 2 to 5 in
      7.6% (23.8% ruptured, 0% ruptured) and 6 in 4.3% of patients. Seventy-two percent
      of aneurysms demonstrated complete occlusion initially, 23.0% had residual neck
      filling, and 4.9% had residual aneurysm filling. CONCLUSION: Endovascular coil
      embolization at a small volume nonspecialized community center is feasible with
      satisfactory procedural risk and clinical outcomes.

PMID- 21848682
TI  - CT angiography source images acquired with a fast-acquisition protocol
      overestimate infarct core on diffusion weighted images in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Studies have demonstrated that computed tomography (CT)
      angiography source images (CTA-SI) acquired under near-steady-state contrast
      concentration provide infarct core estimates equivalent to diffusion-weighted
      images (DWI). We sought to test this relationship using our current CTA protocol
      optimized for faster scan acquisition. METHODS: Forty-eight consecutive acute
      ischemic stroke patients met the following criteria: fast-acquisition CTA and
      magnetic resonance imaging (MRI) within 9 hours of symptom onset, CTA-to-MRI
      interval under 2 hours, and anterior circulation vessel occlusion. Collaterals
      were graded on CTA, and lesion volumes were calculated on CTA-SI, DWI, and MR
      mean transit time (MTT) maps. RESULTS: The mean CTA-to-MRI interval was 36
      minutes (+/- 18 minutes). In paired analysis, lesion volumes on CTA-SI were
      significantly larger than on DWI (45.6 cm3 vs. 29.9 cm3; P < .0001). In 14
      (29.2%) cases, there was major CTA-SI overestimation (>25 cm3 difference) of the
      DWI lesion. Lower collateral score (P = .001), higher National Institutes of
      Health stroke scale (NIHSS) score (P = .01), older age (P = .01), and proximal
      occlusion (P < .05) were univariate predictors of major overestimation, with
      collateral score being the only independent predictor. The interobserver
      agreement was worse for CTA-SI than for DWI (P < .001 for limits of agreement).
      CONCLUSIONS: CTA-SI performed using a fast-acquisition protocol overestimates the
      infarct core on DWI. Substantial differences are observed in over 25% of cases,
      and are associated with reduced collateralization.

PMID- 21848683
TI  - Medicago truncatula mtpt4 mutants reveal a role for nitrogen in the regulation of
      arbuscule degeneration in arbuscular mycorrhizal symbiosis.
AB  - Plants acquire essential mineral nutrients such as phosphorus (P) and nitrogen
      (N) directly from the soil, but the majority of the vascular plants also gain
      access to these mineral nutrients through endosymbiotic associations with
      arbuscular mycorrhizal (AM) fungi. In AM symbiosis, the fungi deliver P and N to
      the root through branched hyphae called arbuscules. Previously we identified
      MtPT4, a Medicago truncatula phosphate transporter located in the periarbuscular
      membrane that is essential for symbiotic phosphate transport and for maintenance
      of the symbiosis. In mtpt4 mutants arbuscule degeneration occurs prematurely and
      symbiosis fails. Here, we show that premature arbuscule degeneration occurs in
      mtpt4 mutants even when the fungus has access to carbon from a nurse plant. Thus,
      carbon limitation is unlikely to be the primary cause of fungal death.
      Surprisingly, premature arbuscule degeneration is suppressed if mtpt4 mutants are
      deprived of nitrogen. In mtpt4 mutants with a low N status, arbuscule lifespan
      does not differ from that of the wild type, colonization of the mtpt4 root system
      occurs as in the wild type and the fungus completes its life cycle. Sulphur is
      another essential macronutrient delivered to the plant by the AM fungus; however,
      suppression of premature arbuscule degeneration does not occur in sulphur
      deprived mtpt4 plants. The mtpt4 arbuscule phenotype is strongly correlated with
      shoot N levels. Analyses of an mtpt4-2 sunn-1 double mutant indicates that SUNN,
      required for N-mediated autoregulation of nodulation, is not involved. Together,
      the data reveal an unexpected role for N in the regulation of arbuscule lifespan
      in AM symbiosis.

PMID- 21848684
TI  - Repression of shade-avoidance reactions by sunfleck induction of HY5 expression
      in Arabidopsis.
AB  - The light environment provides signals that play a critical role in the control
      of stem growth in plants. The reduced irradiance and altered spectral composition
      of shade light promote stem growth compared with unfiltered sunlight. However,
      whereas most studies have used seedlings exposed to contrasting but constant
      light treatments, the natural light environment may exhibit strong fluctuations.
      As a result of gaps in the canopy, plants shaded by neighbours may experience
      sunflecks, i.e., brief periods of exposure to unfiltered sunlight. Here, we show
      that sunflecks are perceived by phytochromes A and B, and inhibit hypocotyl
      growth in Arabidopsis thaliana mainly if they occur during the final portion of
      the photoperiod. By using forward and reverse genetic approaches we found that
      ELONGATED HYPOCOTYL 5, LATE ELONGATED HYPOCOTYL, PHYTOCHROME KINASE SUBSTRATE 4
      and auxin signalling are key players in this response.

PMID- 21848685
TI  - Effects of bosentan on nondigital ulcers in patients with systemic sclerosis.
AB  - BACKGROUND: Bosentan is an oral dual endothelin receptor antagonist, which has
      been shown to be efficacious for preventing new digital ulcers in patients with
      systemic sclerosis (SSc) in two high-quality randomized controlled trials.
      However, its efficacy for nondigital ulcers in SSc remains unknown. OBJECTIVES:
      To evaluate the efficacy of bosentan on nondigital ulcers in patients with SSc.
      METHODS: Bosentan was administered to five patients with SSc with pulmonary
      arterial hypertension, who also had nondigital ulcers refractory to conventional
      treatments. The efficacy of bosentan on nondigital ulcers and its association
      with clinical features of ulcers were analysed. RESULTS: The nondigital ulcers
      refractory to conventional treatments were significantly improved by the
      administration of bosentan in cases surrounded with severe cyanosis. In contrast,
      nondigital ulcers without cyanosis were still refractory to bosentan therapy.
      CONCLUSIONS: Bosentan may be efficacious for accelerating the healing of
      nondigital ulcers with severe cyanosis, suggesting that nondigital ulcers caused
      by severely impaired peripheral circulation are highly responsive to this
      treatment.

PMID- 21848686
TI  - Pretibial myxoedema with autoimmunity and hyperplasia treated with
      glucocorticoids and surgery.

PMID- 21848687
TI  - The 'eyes' or 'goggles' as a clue to the histopathological diagnosis of primary
      lymphocytic cicatricial alopecia.

PMID- 21848688
TI  - Vessel resistance to blood flow in the nailfold in patients with psoriasis: a
      prospective case-control echo Doppler-based study.
AB  - BACKGROUND: Psoriasis is a disease in which endothelial cells seem to play an
      important pathogenic role. No report published to date has examined nail
      vascularity in patients with psoriasis. OBJECTIVES: To evaluate the vascularity
      in the nails of patients with psoriasis treated with classic and biologic
      therapies for comparison with disease-free controls, and to evaluate whether
      there are differences in nail vascularity among patients with and without nail
      involvement. METHODS: We performed a prospective study with two cohorts
      comprising 23 patients with moderate-to-severe psoriasis and 23 controls without
      psoriasis. We measured the nailfold vessel resistance index (NVRI) in each
      subgroup. RESULTS: We found significant differences in the NVRI between patients
      and controls (P<0.001). Among patients with psoriasis, those with nail
      involvement showed a higher mean+/-SD NVRI (0.58+/-0.10) than those without
      (0.52+/-0.45). CONCLUSIONS: Psoriasis decreases the blood flow in nails,
      suggesting that this skin disease confers an independent risk for microvascular
      changes. This outcome may be associated with greater risk of nail-related signs.

PMID- 21848689
TI  - KID syndrome: histopathological, immunohistochemical and molecular analysis of
      precancerous and cancerous skin lesions.

PMID- 21848690
TI  - Can B-domain deletion alter the immunogenicity of recombinant factor VIII? A meta
      analysis of prospective clinical studies.
AB  - BACKGROUND: As a result of the infrequency of inhibitors in previously treated
      patients (PTPs) with hemophilia A and the small size of available clinical
      studies, the immunogenicity of factor (F)VIII products has been difficult to
      assess. OBJECTIVES: A meta-analysis of prospective clinical studies was conducted
      to test the hypothesis that de novo inhibitor incidence differs between PTPs
      receiving full-length recombinant FVIII (FL-rFVIII) and B-domain deleted
      recombinant FVIII (BDD-rFVIII). METHODS: Prospective studies with data on
      inhibitors in PTPs receiving FL-rFVIII or BDD-rFVIII were sought using systematic
      methods including bibliographic database searches. Data were secured from
      published study reports and inquiries to investigators. Between-group differences
      in inhibitor incidence rates were evaluated using mixed effects Cox regression.
      RESULTS: Twenty-nine studies with 3012 total PTPs were included. Patients were at
      risk of de novo inhibitor development for a median of 79 exposure days. A total
      of 35 de novo inhibitors were observed. The cumulative hazard for all de novo
      inhibitors was 1.25% with a 95% confidence interval (CI) of 0.63-1.88%. The
      corresponding rate for high-titer de novo inhibitors [> 5 Bethesda units (BU)]
      was 0.29% (CI, 0.01-0.57%). Exposure to BDD-rFVIII was associated with an
      increased risk of all de novo inhibitors (hazard ratio, 7.26; CI, 2.12-24.9; P =
      0.0016) and of high-titer de novo inhibitors (hazard ratio, 10.8; CI, 2.17-53.7;
      P = 0.0037), compared with FL-rFVIII. CONCLUSIONS: This meta-analysis of
      prospective clinical studies suggests that recombinant FVIII products may differ
      in immunogenicity.

PMID- 21848691
TI  - Surgical scar remodelling after photodynamic therapy using aminolaevulinic acid
      or its methylester: a retrospective, blinded study of patients with field
      cancerization.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a nonsurgical alternative to
      conventional tumour excision for nonmelanoma skin cancers (NMSCs). OBJECTIVES: We
      evaluated whether patients with field cancerization (multiple NMSCs) treated with
      aminolaevulinic acid (ALA) or its methylester (MAL) for that indication had PDT
      induced changes in surgical scars in the treatment field. METHODS: Six adult
      patients with multiple NMSCs and a total of 21 scars from previous excisions were
      studied in a retrospective blinded evaluation from clinical photographs of scar
      response to ALA/MAL-PDT. After a 3-h application of topical 20% ALA or 16.8% MAL
      under occlusion, each field was irradiated with 635-nm light-emitting diode light
      at the fluence of 200Jcm(-2) . Patients underwent one to three PDT sessions per
      field at ~1month intervals, to fields that included scars on the back, thigh,
      arms and neck. Pre- and post-treatment digital photographs of scars were combined
      into 92 pairs that were independently and blindly evaluated by three board
      certified dermatologists. This study was performed at our academic practice at
      the Massachusetts General Hospital. RESULTS: PDT produced a statistically
      significant improvement in scar appearance. The degree of improvement correlated
      with the number of treatment sessions (two or three treatments; P<0.05).
      Improvement after a single treatment was not statistically different from
      baseline ratings (P=0.99). CONCLUSIONS: Surgical scar remodelling and clinical
      improvement may be accomplished via ALA/MAL-PDT, but may require repeated
      treatment sessions. Larger, prospective studies are necessary to confirm the
      effectiveness of PDT for this indication.

PMID- 21848693
TI  - The Simplified Pulmonary Embolism Severity Index (PESI): validation of a clinical
      prognostic model for pulmonary embolism.

PMID- 21848692
TI  - Value assignment of the WHO 6th International Standard for  blood coagulation
      factor VIII and von Willebrand factor in  plasma (07/316).

PMID- 21848694
TI  - The Syk-kinase inhibitor R406 impairs platelet activation and monocyte tissue
      factor expression triggered by heparin-PF4 complex directed antibodies.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare but severe
      complication of heparin therapy in which immunoglobulin G (IgG) antibodies
      against the platelet factor 4-heparin complex activate platelets through the
      FcgammaRIIA receptor. Clustering of FcgammaRIIA initiates signaling cascades
      involving tyrosine kinases including the spleen tyrosine kinase (Syk). Moreover,
      besides the critical role of platelets, the expression of tissue factor (TF) by
      human monocytes triggered by HIT antibodies has been shown to contribute to the
      hypercoagulability and the thrombotic complications in HIT patients. OBJECTIVES:
      We investigated the effect of R406, a small molecule inhibitor of Syk developed
      as a potential treatment of autoimmune diseases, allergic disorders and B-cell
      related hematological malignancies, on FcgammaRIIA-mediated platelet activation.
      To further assess the potential activity of Syk inhibitors in HIT treatment, the
      effect of R406 was also evaluated on HIT antibodies-induced expression of TF and
      procoagulant activity of monocytic cells. RESULTS: We show that R406 is a potent
      inhibitor of platelet signaling and functions initiated by FcgammaRIIA cross
      linking by specific antibodies or by sera from HIT patients. Syk inhibition
      efficiently prevents FcgammaRIIA-induced LAT phosphorylation and activation of
      phosphoinositide 3-kinase, Akt, phospholipase Cgamma2 and p38 MAP-kinase. As a
      consequence, FcgammaRIIA-induced platelet aggregation, granule secretion and
      microparticles production are strongly inhibited by R406. Moreover, the Syk
      inhibitor efficiently impairs the expression of TF and the procoagulant activity
      of human monocytes triggered by HIT antibodies. CONCLUSION: Syk inhibitors may be
      of therapeutic interest in the treatment of HIT by reducing HIT antibodies
      mediated platelet activation and monocyte procoagulant activity.

PMID- 21848695
TI  - Relationship between rumen methanogens and methane production in dairy cows fed
      diets supplemented with a feed enzyme additive.
AB  - AIMS: To investigate the relationship between ruminal methanogen community and
      host enteric methane (CH(4) ) production in lactating dairy cows fed diets
      supplemented with an exogenous fibrolytic enzyme additive. METHODS AND RESULTS:
      Ecology of ruminal methanogens from dairy cows fed with or without exogenous
      fibrolytic enzymes was examined using PCR-denaturing gradient gel electrophoresis
      (PCR-DGGE) analyses and quantitative real-time PCR (qRT-PCR). The density of
      methanogens was not affected by the enzyme additive or sampling times, and no
      relationship was observed between the total methanogen population and CH(4) yield
      (as g per head per day or g kg(-1) DMI). The PCR-DGGE profiles consisted of 26
      distinctive bands, with two bands similar to Methanogenic archaeon CH1270
      negatively correlated, and one band similar to Methanobrevibacter gottschalkii
      strain HO positively correlated, with CH(4) yield. Three bands similar to
      Methanogenic archaeon CH1270 or Methanobrevibacter smithii ATCC 35061 appeared
      after enzyme was added. CONCLUSIONS: Supplementing a dairy cow diet with an
      exogenous fibrolytic enzyme additive increased CH(4) yield and altered the
      composition of the rumen methanogen community, but not the overall density of
      methanogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to
      identify the correlation between methanogen ecology and host CH(4) yield from
      lactating dairy cows.

PMID- 21848696
TI  - The effect of various environmental factors on the ethidium monazite and
      quantitative PCR method to detect viable bacteria.
AB  - AIMS: Ethidium monoazide in combination with quantitative PCR (EMA-qPCR) has been
      considered as a promising method to enumerate viable cells; however, its efficacy
      can be significantly affected by disinfection conditions and various
      environments. In this study, thermal disinfection, osmotic pressure and acids
      with different pH values were systematically investigated to achieve the optimum
      conditions. METHODS AND RESULTS: EMA treatment of pure cultures at low
      concentration (10 MUg ml(-1)) for 20 min resulted in effective differentiation
      between viable and nonviable bacteria and had no effect on viable cells. Heating
      at 85 degrees C for 35 min was the optimum condition that yields inactivated
      Escherichia coli (E. coli) cells that were not detected with EMA-qPCR. Performing
      EMA treatment in high-salt ion environment (sodium chloride concentration >=4%)
      could weaken EMA inhibition effect. Both strong and weak acid solutions could
      react with EMA, change its absorption spectra and influence EMA inhibition
      effect. Because of the sublethal acidification injury, underestimation of cell
      counts were found using EMA-qPCR method, and 40-min incubation in Luria-Bertani
      medium could completely offset this error. CONCLUSION: Our results provided
      optimum EMA treatment, thermal disinfection and environment conditions for EMA
      qPCR and demonstrated the feasibility of this method when enumerating viable
      cells under varied osmotic pressure and pH environment. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Optimum EMA treatment, thermal disinfection and EMA-treated
      environment will be successfully applied in EMA-qPCR. Osmotic pressure and acid
      induced injury can be detected by EMA-qPCR with optimization.

PMID- 21848697
TI  - Disseminated cryptococcosis mimicking a lymphoma.

PMID- 21848699
TI  - Hemojuvelin hemochromatosis receiving iron chelation therapy with deferasirox:
      improvement of liver disease activity, cardiac and hematological function.

PMID- 21848698
TI  - Characterization of a thermally stable and organic solvent-adaptative NAD+ 
      dependent formate dehydrogenase from Bacillus sp. F1.
AB  - AIMS: To characterize a robust NAD(+) -dependent formate dehydrogenase firstly
      obtained from a nonmethylotroph, Bacillus sp. F1. METHODS AND RESULTS: The
      Bacillus sp. F1 NAD(+) -dependent formate dehydrogenase (BacFDH) gene was cloned
      by TAIL-PCR and heterologous expressed in Escherichia coli. BacFDH was stable at
      temperatures below 55 degrees C, and the half-life at 60 degrees C was determined
      as 52.9 min. This enzyme also showed a broad pH stability and retained more than
      80% of the activities after incubating in buffers with different pH ranging from
      4.5 to 10.5 for 1 h. The activity of BacFDH was significantly enhanced by some
      metal ions. Moreover, BacFDH exhibited high tolerance to 20% dimethyl sulfoxide,
      60% acetone, 10% methanol, 20% ethanol, 60% isopropanol and 20% n-hexane. Like
      other FDHs, BacFDH displayed strict substrate specificity for formate.
      CONCLUSION: We isolated a robust formate dehydrogenase, designated as BacFDH,
      which showed excellent thermal stability, organic solvent stability and a broad
      pH stability. SIGNIFICANCE AND IMPACT OF THE STUDY: The multi-aspect stability
      makes BacFDH a competitive candidate for coenzyme regeneration in practical
      applications of chiral chemicals and pharmaceuticals synthesis with a relatively
      low cost, especially for the catalysis performed in extreme pH conditions and
      organic solvents.

PMID- 21848700
TI  - Allogeneic bone marrow vs. peripheral blood stem cell transplantation: a long
      term retrospective single-center analysis in 329 patients.
AB  - OBJECTIVES: Granulocyte colony-stimulating factor-mobilized peripheral blood
      hematopoietic stem cell transplantation (HSCT) provides a valuable and
      increasingly used alternative to bone marrow transplantation (BMT). This
      retrospective study aimed at determining whether the stem cell source is
      predictive for outcome, relapse incidence, non-relapse mortality, and severity
      and incidence of both, acute and chronic graft-versus-host disease (GVHD) in
      patients undergoing allogeneic HSCT. PATIENTS AND METHODS: Between 1983 and 2007,
      329 adult patients (median age 40, range 18-76) received a first allogeneic HSCT
      from either sibling (n = 203) or volunteer unrelated donors (n = 126) at our
      institution. The source of stem cells was bone marrow in 177 (54%) and peripheral
      blood in the remaining 152 (46%) patients. RESULTS: Overall survival was 37% (31
      43%, 95% confidence interval, CI), the relapse incidence was 30% (25-36%, 95%
      CI), and the non-relapse mortality was 43% (38-49%, 95% CI) for the entire cohort
      with no significant differences between peripheral blood stem cell or BMT. In
      patients receiving myeloablative conditioning, peripheral blood stem cell
      transplantation (PBSCT) was associated with a significantly lower non-relapse
      mortality (32% vs. 46%, P = 0.05), which, however, was restricted to standard
      risk disease (23% vs. 42%, P = 0.02). The overall cumulative incidences of acute
      GVHD II-IV were 51% and 54% following bone marrow and PBSCT, respectively. Severe
      acute GVHD III-IV was significantly more frequent after BMT (24% vs. 14%, P =
      0.04), whereas chronic GVHD was significantly more frequent following PBSCT (48%
      vs. 24%, P = 0.0001). By multivariate analysis, PBSCT was only predictive for
      chronic GVHD (RR 2.29, P = 0.02). CONCLUSION: Although we failed to demonstrate
      any advantage of PBSCT over conventional BMT with regard to overall survival,
      relapse incidence and non-relapse mortality PBSCT were associated with a
      significantly higher incidence of chronic graft-versus-host disease. Therefore,
      and by virtue of observations, that some patient groups might benefit from either
      stem cell source, there is still need for prospective randomized trials with
      special emphasize on quality of life in long-term survivors.

PMID- 21848701
TI  - Functional genetic variations of cyclooxygenase-2 and susceptibility to acute
      myeloid leukemia in a Chinese population.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the synthesis of
      prostaglandins, which are known to play important roles in the proliferation and
      differentiation of leukemia cells, and inhibitors of COX-2 can suppress the
      proliferation and differentiation of human leukemia cell lines. Single-nucleotide
      polymorphisms (-765G/C: rs20417, -1195A/G: rs689466, and -1290A/G: rs689465) in
      the COX-2 promoter might contribute to differential COX-2 expression and
      subsequent interindividual variability in susceptibility to cancer. METHODS: In
      this case-control study, the genotypes of potential functional Single-nucleotide
      polymorphisms in COX-2 gene were determined with PCR-RFLP method in 446 patients
      and 725 controls. COX-2 mRNA level in Acute myeloid leukemia (AML) bone marrow
      and COX-2 protein level in serum samples were examined by real-time PCR and
      ELISA, respectively. RESULTS: It was found that carriers with -765CC genotypes
      had a 2.19-fold (95% CI = 1.24-3.88; P < 0.001) excess risk of developing AML
      compared with non-carriers. A greater risk of developing AML was observed for A(
      1195) -C(-765) haplotype compared with G(-1195) -G(-765) haplotype. Moreover,
      individuals with -765C-containing genotypes had significantly increased COX-2
      mRNA level and protein level compared with the -765G-containing counterparts.
      CONCLUSIONS: These findings indicate that -765G/C polymorphism in COX-2 may play
      a vital role in mediating individual susceptibility to AML.

PMID- 21848702
TI  - Neurocognitive impairment and psychosocial functioning in bipolar II disorder.
AB  - OBJECTIVE: There is a growing body of evidence on neurocognitive impairment in
      euthymic bipolar patients, but this issue has been studied mostly in bipolar I
      disorder, data on bipolar II (BD-II) are scant and discrepant. The two aims of
      this study were to ascertain whether strictly defined euthymic BD-II patients
      would present neurocognitive disturbances and to evaluate their impact on
      functional outcome. METHOD: Forty-three BD-II patients and 42 demographically and
      educationally matched healthy subjects were assessed with a comprehensive
      neuropsychological test battery and with the Social and Occupational Functioning
      Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating
      Scale for Depression score <=6 and a Young Mania Rating Scale score <=6) to
      minimize the influence of subdepressive symptomatology on cognition and
      functioning. RESULTS: BD-II patients showed a significantly lower performance on
      several measures of attention, learning and verbal memory, and executive function
      compared with healthy controls. The presence of subthreshold depressive
      symptomatology and one measure related to executive function (Trail Making Test,
      part B) was the variables that best predicted psychosocial functioning measured
      with the SOFAS. CONCLUSION: This report provides further evidence that euthymic
      BD-II patients present cognitive impairment which may impact psychosocial
      functioning.

PMID- 21848703
TI  - Childhood maltreatment and clinical outcomes of bipolar disorder.
AB  - OBJECTIVE: Adverse life events, especially early trauma, play a major role in the
      course and expression of bipolar disorder (BD). The aim of this article is to
      present a systematic review about the impact of childhood trauma on the clinical
      course of BD. METHOD: A computer-aided search was performed in Medline, ISI
      database, EMBASE, PsychInfo, Centre for Reviews and Dissemination, and Databases
      of Thomson Reuters at April 2011, supplemented by works identified from the
      reference lists of the first selected papers. Two investigators systematically
      and independently examined all articles, selecting those according inclusion and
      exclusion criteria. RESULTS: Four hundred fifteen articles were identified, of
      which 19 remained in the review after exclusion criteria were applied. In
      general, childhood maltreatment predicted worsening clinical course of BD. After
      assessing the quality of the data and of the measurements, childhood maltreatment
      can be strongly associated to early onset of disorder, suicidality, and substance
      abuse disorder in patients with BD. CONCLUSION: Data suggest that childhood abuse
      and neglect are risk factors associated with worsening clinical course of BD. The
      conclusions should be interpreted with caution because all the studies included
      are cross-sectional and the majority are showing inconsistencies regarding
      childhood trauma as independent variable and how it is assessed.

PMID- 21848704
TI  - Incidence and lifetime risk of dementia and Alzheimer's disease in a Southern
      European population.
AB  - OBJECTIVE: To calculate both the incidence rates and the lifetime risk (LTR) of
      dementia and Alzheimer's disease (AD). METHODS: A two-phase case-finding
      procedure was implemented in a cohort of 4057 cognitively intact individuals 55+
      years of age living in Zaragoza, Spain, and followed-up at 2.5 and 4.5 years. Age
      and sex-specific incidence rates were calculated. A mortality-adjusted,
      multivariate model was used to document LTRs. RESULTS: The incidence rate of
      dementia continued to rise after the age of 90 years, but was slightly lower than
      in North and West European studies. Only a tendency for an increased LTR with age
      was observed. Thus, LTR was 19.7% for a 65-year-old woman and 20.4% at the age of
      85 years, the corresponding figures for AD being 16.7% and 17.6%. The LTR of AD
      was higher in women and was about twice as high among illiterate individuals when
      compared with individuals with higher educational levels. CONCLUSIONS: The
      incidence rate of dementia in this Southern European city was slightly lower than
      in previous studies in North-West Europe. LTR of dementia and AD seems to be
      slightly increased with age. The association of illiteracy with higher LTR of AD
      is intriguing.

PMID- 21848705
TI  - Positive and negative life events and personality traits in predicting course of
      depression and anxiety.
AB  - OBJECTIVE: To examine the prognostic value of personality dimensions and negative
      and positive life events for diagnostic and symptom course trajectories in
      depressive and anxiety disorder. METHOD: A total of 1209 subjects (18-65 years)
      with depressive and/or anxiety disorder were recruited in primary and specialized
      mental health care. Personality dimensions at baseline were assessed with the NEO
      FFI and incidence and date of life events retrospectively with a structured
      interview at 2-year follow-up. DSM-IV-based diagnostic interviews as well as life
      chart assessments allowed course assessment at both the diagnostic and symptom
      trajectory level over 2 years. RESULTS: Life events were significantly related to
      diagnostic and symptom course trajectories of depression and anxiety also after
      correcting for sociodemographic and clinical characteristics. Only negative life
      events prospectively predicted longer time to remission of depressive disorder.
      Prospective associations of neuroticism and extraversion with prognosis of
      anxiety and depression were greatly reduced after correcting for baseline
      severity and duration of index disorder. Personality traits did not moderate the
      effect of life events on 2-year course indicators. CONCLUSIONS: Negative life
      events have an independent effect on diagnostic and symptom course trajectories
      of depression and to a lesser extent anxiety unconfounded by sociodemographic,
      clinical, and personality characteristics.

PMID- 21848706
TI  - Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Roflumilast, an oral, selective phosphodiesterase 4
      inhibitor, has been shown to reduce exacerbations and improve pulmonary function
      in patients with COPD. This study examined the efficacy, safety and tolerability
      of roflumilast in Asian patients with COPD. METHODS: Patients with COPD were
      randomized 1:1 to enter a 12-week treatment period and receive either oral
      roflumilast, 500 ug once daily, or placebo, following a single-blind, 4-week
      baseline period in which all patients received placebo. The primary end point was
      mean change in FEV1 from baseline to each postrandomization visit during the
      treatment period. Other spirometric lung function measurements were evaluated as
      secondary end points. COPD exacerbations were monitored. Safety was assessed from
      clinical laboratory tests, vital signs, physical examination (including
      electrocardiogram) and monitoring of adverse events (AEs). RESULTS: Of 551
      patients recruited, 410 were randomized and received at least one dose of study
      medication (roflumilast, n = 203; placebo, n = 207). Superiority of roflumilast
      over placebo was demonstrated by a statistically significant difference in
      postbronchodilator FEV1 (79 mL, P < 0.0001). Other spirometry end points,
      including prebronchodilator FEV1, pre-and postbronchodilator FEV6, forced vital
      capacity and peak expiratory flow significantly favoured roflumilast over
      placebo. AEs were more common with roflumilast than with placebo, but were
      comparable with those reported in previous studies. CONCLUSIONS: Roflumilast, 500
      ug once daily, improves pulmonary function in Asian patients with COPD. The
      safety and tolerability of roflumilast in this population was similar to that in
      a Caucasian population.

PMID- 21848707
TI  - Phenotypes of patients with mild to moderate obstructive sleep apnoea as
      confirmed by cluster analysis.
AB  - BACKGROUND AND OBJECTIVE: Patients with OSA manifest different patterns of
      disease. However, this heterogeneity is more evident in patients with mild
      moderate OSA than in those with severe disease and a high total AHI. We
      hypothesized that mild-moderate OSA can be categorized into discreet disease
      phenotypes, and the aim of this study was to comprehensively describe the pattern
      of OSA phenotypes through the use of cluster analysis techniques. METHODS: The
      data for 1184 consecutive patients, collected over 24 months, was analysed.
      Patients with a total AHI of 5-30/h were categorized according to the sleep stage
      and position in which they were predominantly affected. This categorization was
      compared with one in which patients were grouped using a K-means clustering
      technique with log linear modelling and cross-tabulation. RESULTS: Patients with
      mild-moderate OSA can be categorized according to polysomnographic parameters.
      This clinical categorization was validated by comparison with a categorization in
      which patients were grouped by unsupervised K-means cluster analysis. The
      clinical groups identified were: (i) rapid eye movement (REM) predominant OSA,
      44.6%; (ii) non-REM predominant OSA, 18.9%; (iii) supine predominant OSA, 61.9%;
      and (iv) intermittent OSA, 12.4%. Patients categorized as having both REM and
      supine predominant OSA showed characteristics of both the REM predominant and
      supine predominant OSA groups. CONCLUSIONS: Patients with mild-moderate OSA show
      different polysomnographic phenotypes. This approach to categorization more
      appropriately reflects disease heterogeneity and the likely multiple
      pathophysiological processes involved in OSA.

PMID- 21848708
TI  - Increasing antibiotic resistance in Streptococcus pneumoniae colonizing children
      attending day-care centres in Singapore.
AB  - BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae is an important cause of
      morbidity and mortality in both the paediatric and adult population. This study
      aimed to define pneumococcal colonization rates, and antibiotic resistance
      patterns across two periods a decade apart, and also assess the serotypes of
      colonizing strains in children in the era of early pneumococcal conjugate vaccine
      uptake in Singapore. METHODS: Two cross-sectional prevalence surveys were carried
      out in 1997 and 2007-2008 on children attending day-care centres across
      Singapore. Nasopharyngeal swabs were obtained and cultured for S. pneumoniae, and
      antibiotic susceptibility testing was performed. Serotyping was also done in the
      2007-2008 survey. RESULTS: Three hundred and ninety-five children participated in
      the first survey in 1997, and 418 in the 2007-2008 survey. Pneumococcal
      colonization rates were 25.8 and 14.1%, respectively. There was a marked increase
      in antimicrobial non-susceptibility (penicillin 27.4% vs 69.5%; erythromycin
      33.4% vs 78%; clindamycin 24.5% vs 45.8%, tetracycline 48% vs 67.8%), and multi
      drug resistance (defined as non-susceptibility to three or more classes of
      antibiotics) increased from 33.3 to 74.6%. In the 2007-2008 survey, serotypes 6B
      (16.9%), 23F (11.9%) and 19F (10.2%) were most commonly observed. The projected
      coverage of the 7 and 13-valent conjugate pneumococcal vaccine for colonizing
      serotypes were 61.9 and 67%, respectively. CONCLUSIONS: S. pneumoniae antibiotic
      resistance has risen dramatically over the last 10 years in Singapore. Wider
      conjugate vaccine uptake and improved antibiotic stewardship should be made
      priorities. Surveillance of sentinel sites like day-care centres provides
      important data with respect to shifts in pneumococcal ecology.

PMID- 21848709
TI  - Pleural fluid nucleic acid testing enhances pneumococcal surveillance in
      children.
AB  - BACKGROUND AND OBJECTIVE: National surveillance of invasive pneumococcal disease
      (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile
      site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in
      culture-negative samples. The aim of this study was to determine whether enhanced
      surveillance of childhood empyema, using PCR, provides additional serotype
      information compared with conventional surveillance. METHODS: Pleural fluid (PF)
      from children with empyema were cultured and tested by PCR to identify SP,
      targeting the autolysin gene (lytA). Multiplex PCR-based reverse line blot assay
      was used to identify SP STs. Corresponding IPD surveillance and serotype data
      were obtained from the National Notifiable Diseases Surveillance System (NNDSS).
      RESULTS: Eighty-nine children with empyema, aged <=16 years, were recruited
      between April 2008 and March 2009, inclusive. SP was isolated from 5/84 (5.9%) PF
      cultures and by PCR in 43/79 (54.4%) PF samples. Serotypes were unidentifiable in
      15 samples. The frequency of six serotypes (or serotype pairs) identified in 28
      samples, including one with two serotypes, were: ST1, n = 4/29 (13.8%); ST3, n =
      9/29 (31.0%); ST19A, n = 12/29 (41.4%); ST7F/7A, n = 1/29 (3.4%); ST9V/9A, n =
      1/29 (3.4%); ST22F/22A, n = 2/29 (6.9%). Over the same period, 361 IPD patients,
      aged 16 years or less, were notified to NNDSS. Among 331 serotypeable NNDSS
      isolates (71.5% from blood), the frequencies of ST1 and 3 were significantly
      lower than in PF samples: ST1, n = 8/331 (2.4%; P < 0.05); ST3, n = 13/331 (3.9%;
      P < 0.0001). CONCLUSIONS: The use of PCR to identify and serotype SP in culture
      negative specimens provides additive information.

PMID- 21848711
TI  - Pass/fail grading: not everything that counts can be counted.

PMID- 21848712
TI  - Feedback: much more than a tool.

PMID- 21848713
TI  - Getting closer to the real thing.

PMID- 21848714
TI  - Impact of pass/fail grading on medical students' well-being and academic
      outcomes.
AB  - OBJECTIVES: Many medical schools are currently undergoing curriculum reform. When
      considering the means by which students will be evaluated in a revised
      curriculum, the need to reduce the prevalences of depression and anxiety
      associated with academic stress must be weighed against the importance of
      academic outcomes. Pass/fail evaluation, as compared with tiered grading, is
      commonly presented as a means to adequately assess student performance while
      minimising stress and anxiety. The purpose of this literature review was to
      determine the impact of pass/fail grading on medical student well-being and
      academic outcomes. METHODS: A systematic search was performed of the available
      literature published between January 1980 and August 2010, using the PubMed, Ovid
      Medline, Ovid PsycINFO and ERIC databases. Eligible papers assessed the impact of
      pass/fail grading on medical student well-being, academic outcomes or both.
      Academic outcomes included but were not limited to objective measures, such as
      performance on the US Medical Licensing Examination, and subjective measures,
      such as student desirability by residency programmes. Reference lists in
      identified papers were searched and all identified papers were run through a
      citation index. RESULTS: Four papers met the inclusion criteria for both well
      being and academic outcomes. An additional five papers met the inclusion criteria
      for academic outcomes only. The four papers that focused on well-being reported
      improvement in specified areas. No significant difference was identified in any
      of the five papers examining objective academic outcomes or in those papers that
      examined the quality of residency programmes attained. Results from two studies
      suggested that some programme directors believe pass/fail grading creates
      disadvantages for students in attaining a residency, whereas a third study
      yielded mixed results about its impact on residency attainment. CONCLUSIONS:
      Student well-being is enhanced and objective academic performance is not
      adversely affected by a pass/fail evaluation system, but students' ability to
      obtain a desired residency programme may be hindered by individual programme
      directors' preferences for tiered grading systems. There is an overall paucity of
      literature on this topic and additional study is needed.

PMID- 21848715
TI  - Clinical skills-related learning goals of senior medical students after
      performance feedback.
AB  - CONTEXT: Lifelong learning is essential for doctors to maintain competence in
      clinical skills. With performance feedback, learners should be able to formulate
      specific and achievable learning goals in areas of need. OBJECTIVES: We aimed to
      determine: (i) the type and specificity of medical student learning goals after a
      required clinical performance examination; (ii) differences in goal setting among
      low, average and high performers, and (iii) whether low performers articulate
      learning goals that are concordant with their learning needs. METHODS: We
      conducted a single-site, multi-year, descriptive comparison study. Senior medical
      students were given performance benchmarks, individual feedback and guidelines on
      learning goals; each student was subsequently instructed to write two clinical
      skills learning goals. Investigators coded the learning goals for specificity,
      categorised the goals, and performed statistical analyses to determine their
      concordance with student performance level (low, average or high) in data
      gathering (history taking and physical examination) or communication skills.
      RESULTS: All 208 students each wrote two learning goals and most (n=200, 96%)
      wrote two specific learning goals. Nearly two-thirds of low performers in data
      gathering wrote at least one learning goal that referred to history taking or
      physical examination; one-third wrote learning goals pertaining to the
      organisation of the encounter. High performers in data gathering wrote
      significantly more patient education goals and significantly fewer history-taking
      goals than average or low performers. Only 50% of low performers in communication
      wrote learning goals related to communication skills. Low performers in
      communication were significantly more likely than average or high performers to
      identify learning goals related to improving performance in future examinations.
      CONCLUSIONS: The provision of performance benchmarking, individual feedback and
      brief written guidelines helped most senior medical students in our study to
      write specific clinical skills learning goals. Many low-performing students did
      not write learning goals concordant with their areas of weakness. Future work
      might focus on enhancing low performers' continued learning in areas of
      performance deficits.

PMID- 21848716
TI  - Factors that might undermine the validity of patient and multi-source feedback.
AB  - CONTEXT: Multi-source feedback (MSF) and patient feedback (PF) are used
      increasingly around the world to assess and quality-assure clinical practice.
      However, concerns about the evidence for their utility pertain to their ability
      to identify poor performance, the impact of allowing assessees to select their
      own assessors and the many confounders that may undermine validity. METHODS: This
      study was conducted in conjunction with the National Clinical Assessment Service
      (NCAS) in the UK and used established MSF and PF instruments to assess doctors in
      potential difficulty. Multi-source feedback assessors were nominated by both the
      practitioner (Pnom) and the referring body (RBnom). Demographics were collected
      to elucidate any differences found. Ratings generated by MSF and PF were compared
      with one another and with findings of a previous study that provided a normative
      cohort. RESULTS: Using MSF, NCAS-assessed doctors scored significantly lower than
      the reference cohort. Nineteen (28%) NCAS-assessed doctors achieved scores that
      were less than satisfactory. This rose to 50% when only RBnom assessors were
      used. Overall, ratings awarded by RBnom assessors were significantly lower than
      those awarded by Pnom assessors. Collected demographics did not help to explain
      the difference. Only one NCAS-assessed doctor scored below average according to
      PF. Doctors in the NCAS-assessed group did not score significantly lower than the
      reference cohort in PF. Doctor assessment scores awarded by patients were
      significantly higher than those awarded by colleagues. CONCLUSIONS: Although
      colleagues appear to report poor performance using MSF, patients fail to report
      concurrent findings. This challenges the validity of PF as it is currently
      constructed. Scores in MSF differ significantly depending on whether they are
      practitioner- or third party-nominated. Previously recognised confounding factors
      do not help to explain this difference.

PMID- 21848717
TI  - Effectiveness of past and current critical incident analysis on reflective
      learning and practice change.
AB  - OBJECTIVES: Critical incident analysis (CIA) is one of the strategies frequently
      used to facilitate reflective learning. It involves the thorough description and
      analysis of an authentic and experienced event within its specific context.
      However, CIA has also been described as having the potential to expose
      vulnerabilities, threaten learners' coping mechanisms and increase rather than
      reduce their anxiety levels. The aim of this study was to compare the analysis of
      current critical incidents with that of past critical incidents, and to further
      explore why and how the former is more conducive to reflective learning and
      practice change than the latter. METHODS: A collaborative research study was
      conducted. Eight occupational therapists were recruited to participate in a
      reflective learning group that convened for 12 meetings held over a 15-month
      period. The group facilitator planned and adapted the learning strategies to be
      used to promote reflective learning and guided the group process. Critical
      incident analysis represented the main activity carried out in the group
      discussions. The data collected were analysed using the grounded theory method.
      RESULTS: Three phenomena were found to differentiate between the learning
      contexts created by the analysis of, respectively, past and current critical
      incidents: attitudinal disposition; legitimacy of purpose, and the availability
      of opportunities for experimentation. Analysis of current clinical events was
      found to improve participants' motivation to self-evaluate, to increase their
      self-efficacy, and to help them transfer learning into action and to
      progressively self-regulate. CONCLUSIONS: The results of this collaborative
      research study suggest that the analysis of current clinical events in order to
      promote reflection offers a safer and more constructive learning environment than
      does the analysis of incidents that have occurred in the past. This learning
      strategy is directly grounded in health professional practice. The remaining
      challenge for continuing education providers is that of creating conditions
      conducive to its use.

PMID- 21848718
TI  - Specialty differences in the association between health care climate and patient
      trust.
AB  - CONTEXT: Previous studies have suggested that there is a positive correlation
      between doctors' emotional intelligence (EI) and patients' trust in their
      attending physicians; however, there is only limited evidence of specialty
      differences between internists and surgeons for such an association. OBJECTIVES:
      This study examined the association of nursing director assessments of doctors'
      EI, outside observer assessments of doctors' health care climate (HCC) in the
      examining room and patient-rated trust in internists and surgeons. Health care
      climate refers to a key component in communication and reflects the extent to
      which patients perceive their health care providers as supporting patient
      autonomy rather than controlling the provision of treatment. METHODS: In this
      observational study, 2702 patients seen by 110 internists and 2642 patients seen
      by 101 surgeons were surveyed in face-to-face interviews by trained nurses in two
      teaching hospitals in Taiwan. Using hierarchical linear modelling, we examined
      the association between EI and HCC as well as patient trust in doctors working in
      the specialties of internal medicine and surgery. RESULTS: We found a
      significantly positive correlation between doctor EI and patient trust for all
      patients (p<0.01). In addition, although HCC was positively associated with
      patient trust for internists (p<0.01), it was not so for surgeons. CONCLUSIONS:
      We conclude that doctors might benefit from training programmes aimed at
      improving EI and that differences in patient expectations might be considered
      when hospitals attempt to evaluate doctors in different specialties.

PMID- 21848719
TI  - Learning from patients: students' perceptions of patient-instructors.
AB  - OBJECTIVES: Prior research on the use of patients as teachers has focused on
      testing the effectiveness of this practice and exploring its benefits for
      students. However, very little is known about the added value of patient teaching
      and how it relates to patient-centred learning. The aim of this study was to
      explore whether there is added value in using patients as instructors in health
      professions education and, if there is, to examine how it is constituted.
      METHODS: Group interviews were conducted with physiotherapy and occupational
      therapy students who had attended a 3-hour optional class entitled 'Thoughtful
      joint examination and respectful patient contact'. This class was delivered by
      patient-instructors (PIs), who were patients with rheumatism certified to teach.
      A semi-structured interview guide was used. Interviews continued until data
      saturation occurred (seven interviews). The interviews were recorded and
      transcribed verbatim. Data were analysed using content analysis. RESULTS: The
      main finding of this study is that PI sessions facilitate a learning environment
      in which the content matter is complemented by the provision of realism and
      individual perspectives on rheumatism, the pedagogical format is characterised by
      authenticity and intimacy in the style of instruction and feedback, and the PI
      student relationship is characterised by balanced teacher-student power relations
      that support the legitimacy of learning and make space for the asking of
      questions and the making of mistakes. CONCLUSIONS: This study indicates that, in
      terms of power relations, the PI-student relationship differs from those between
      faculty teachers and students, and students and patients in the clinic. The
      formation of a professional identity by students may clash with the fulfilment of
      their learning tasks in the clinical environment. The study indicates that
      patient-centredness can be fostered in the PI-student relationship. This is
      probably supported by the absence of faculty staff involvement in PI teaching
      sessions. However, further empirical research is required on what, how and why
      students learn from patients in different learning contexts.

PMID- 21848720
TI  - Putting the expert together again.
AB  - CONTEXT: The study of expertise in medical education has a long history of
      success. Researchers have identified and elaborated on many dimensions of expert
      performance. In part, this success has derived from researchers' ability to
      effectively isolate the dimensions and explore each separately. Although this
      deconstruction of the expert has been successful, the need to recombine the
      dimensions of expertise as part of an integrated construct of expert practice has
      recently become an increasingly evident imperative in health professions
      education. METHODS: The aims of this paper are first to explore dimensions of
      expert practice as they are expressed in the expertise literature; secondly, to
      describe more recent programmes of research that have tried to elaborate on how
      experts integrate these various dimensions during daily practice, and, finally,
      to examine the potential implications of research exploring how experts integrate
      their own knowledge and skills with the affordances of the environment in which
      they work. RESULTS AND CONCLUSIONS: There are both challenges and opportunities
      in elaborating an integrated discourse on expertise. Exploring directions for
      research related to this integrated construction of the practising expert may add
      an important dimension to our educational repertoire.

PMID- 21848721
TI  - Context and clinical reasoning: understanding the perspective of the expert's
      voice.
AB  - OBJECTIVES: Prior work has found that a doctor's clinical reasoning performance
      varies on a case-by-case (situation) basis; this is often referred to as 'context
      specificity'. To explore the influence of context on diagnostic and therapeutic
      clinical reasoning, we constructed a series of videotapes to which doctors were
      asked to respond, modifying different contextual factors (patient, doctor,
      setting). We explored how these contextual factors, as displayed by videotape
      encounters, may have influenced the clinical reasoning of board-certified
      internists (experts). Our purpose was to clarify the influence of context on
      reasoning, to build upon education theory and to generate implications for
      education practice. METHODS: Qualitative data about experts were gathered from
      two sources: think-aloud protocols reflecting concurrent thought processes that
      occurred while board-certified internists viewed videotape encounters, and free
      text responses to queries that explicitly asked these experts to comment on the
      influence of selected contextual factors on their clinical reasoning processes.
      These data sources provided both actual performance data (think-aloud responses)
      and opinions on reflection (free-text answers) regarding the influence of context
      on reasoning. Results for each data source were analysed for emergent themes and
      then combined into a unified theoretical model. RESULTS: Several themes emerged
      from our data and were broadly classified as components influencing the impact of
      contextual factors, mechanisms for addressing contextual factors, and
      consequences of contextual factors for patient care. Themes from both data
      sources had good overlap, indicating that experts are somewhat cognisant of the
      potential influences of context on their reasoning processes; notable exceptions
      concerned the themes of missed key findings, balancing of goals and the influence
      of encounter setting, which emerged in the think-aloud but not the free-text
      analysis. CONCLUSIONS: Our unified model is consistent with the tenets of
      cognitive load, situated cognition and ecological psychology theories. A number
      of potentially modifiable influences on clinical reasoning were identified.
      Implications for doctor training and practice are discussed.

PMID- 21848722
TI  - Teaching operating room conflict management to surgeons: clarifying the optimal
      approach.
AB  - CONTEXT: Conflict management has been identified as an essential competence for
      surgeons as they work in operating room (OR) teams; however, the optimal approach
      is unclear. Social science research offers two alternatives, the first of which
      recommends that task-related conflict be managed using problem-solving techniques
      while avoiding relationship conflict. The other approach advocates for the active
      management of relationship conflict as it almost always accompanies task-related
      conflict. Clarity about the optimal management strategy can be gained through a
      better understanding of conflict transformation, or the inter-relationship
      between conflict types, in this specific setting. The purpose of this study was
      to evaluate conflict transformation in OR teams in order to clarify the approach
      most appropriate for an educational conflict management programme for surgeons.
      METHODS: A constructivist grounded theory approach was adopted to explore the
      phenomenon of OR team conflict. Narratives were collected from focus groups of OR
      nurses and surgeons at five participating centres. A subset of these narratives
      involved transformation between and within conflict types. This dataset was
      analysed. RESULTS: The results confirm that misattribution and the use of harsh
      language cause conflict transformation in OR teams just as they do in stable work
      teams. Negative emotionality was found to make a substantial contribution to
      responses to and consequences of conflict, notably in the swiftness with which
      individuals terminated their working relationships. These findings contribute to
      a theory of conflict transformation in the OR team. CONCLUSIONS: There are a
      number of behaviours that activate conflict transformation in the OR team and a
      conflict management education programme should include a description of and
      alternatives to these behaviours. The types of conflict are tightly interwoven in
      this setting and thus the most appropriate management strategy is one that
      assumes that both types of conflict will exist and should be managed actively.

PMID- 21848723
TI  - Role-modelling in the operating room: medical student observations of exemplary
      behaviour.
AB  - CONTEXT: Training future doctors to develop an appropriate professional persona
      is an important goal of medical student education and residency training. Most
      medical education research paradigms on professionalism have focused largely on
      lapses (e.g. yelling as an example of communication failure) and tend to
      emphasise behaviour that should be avoided. The assumption is that, if left
      unchecked, students will see these negative behaviours exhibited by their role
      models and possibly emulate them, allowing the potential reinforcement of the
      inappropriate behaviours. OBJECTIVES: Identifying and characterising exemplary,
      or positive, behaviours can be similarly valuable to both medical students and
      residents as tangible examples of behaviours to strive towards. The goal of the
      present research was to determine and thematically define the exemplary
      professional actions that medical students observe in the intense and patient
      focused environment of the operating room (OR). METHODS: Using qualitative
      methodology of content analysis and theme identification, we systematically
      documented the type of exemplary professional behaviours reported by medical
      students (n=263) when observing health care teams on an anaesthesia rotation in
      the OR. RESULTS: The analysis generated a taxonomy of exemplary OR behaviour that
      included six overarching themes (e.g. teamwork), 15 sub-themes (e.g. collegial)
      and numerous exemplars (e.g. showed mutual respect). These themes and sub-themes
      were then conceptually 'matched'--through the use of antonyms --to complement an
      existing framework focused on medical student reports of professional lapses
      witnessed during medical school. CONCLUSIONS: Year 3 medical students in the USA
      reported observing very positive, exemplary health care provider interactions
      that were diverse in focus. Themes were identified regarding the OR team members'
      interactions with patients (calm, communication, comforting), with one another
      (teamwork, respect) and with the medical students (teaching). This classification
      of exemplary OR behaviour contributes to our understanding of how professional
      behaviour is viewed and potentially emulated by medical students on surgical
      rotations.

PMID- 21848724
TI  - Skilled communication: comments further to 'Creativity in clinical communication:
      from communication skills to skilled communication'.

PMID- 21848725
TI  - Unskilled creativity is counterproductive.

PMID- 21848727
TI  - The challenges of managing complex lymphoedema/chronic oedema in the UK and
      Canada.
AB  - This article explores the professional challenges of treating patients with
      complex/severe forms of chronic oedema/lymphoedema with compression therapy. Four
      focus groups were held, two in the UK and two in Canada, to examine the
      challenges faced by practitioners in their everyday practice. A number of
      challenges were identified by participants in both countries and include the
      changing profile of lymphoedema/chronic oedema and how increasing complexity is
      outpacing the development of services and research-based guidelines. Focus groups
      also highlighted a lack of public awareness, poor professional knowledge, delayed
      diagnosis and inappropriate treatment as having a significant impact on practice.
      Other practice-related issues include a poor understanding of treatment options
      among practitioners, a lack of evidence-based practice as well as difficulties
      associated with managing psychosocial problems and of ensuring concordance with
      treatment. In Canada, services tend to be more rural and remote than in the UK,
      autonomous specialist practice is less developed and practitioners were generally
      less confident and felt more vulnerable than their UK colleagues. There is a need
      for integrated, multi-disciplinary services in both countries, with improved
      education and training, as well as the development of cost-effective compression
      bandaging systems that can make a major contribution to meeting the challenges of
      contemporary lymphoedema practice.

PMID- 21848728
TI  - The experience of patients with lymphoedema undergoing a period of compression
      bandaging in the UK and Canada using the 3MTM CobanTM 2 compression system.
AB  - This article reports on a qualitative study that explored the experience of
      patients who have undergone a period of complete decongestive therapy using the
      3MTM CobanTM 2 compression system (Coban 2 system). Qualitative data were
      collected from 12 patients from the UK and 8 from Canada with a range of
      presentations of lymphoedema. Single semi-structured interviews were used and
      participants were asked questions relating to their experience of diagnosis, the
      impact of lymphoedema on their lives, previous treatment using multilayer
      lymphoedema bandaging and their experiences of the 3MTM CobanTM 2 system.
      Treatment with multilayer lymphoedema bandaging was seen as constraining in that
      it was tiring, time consuming, heavy, bulky and led to feelings of clumsiness and
      a restricted life. Treatment with the 3MTM CobanTM 2 system was reported as
      enabling in that it was quicker and easier to apply, increased mobility, enhanced
      patient confidence and provided a sense of control and well-being. The article
      also explores how aspects of the 3MTM CobanTM 2 system might be improved from the
      patient's point of view.

PMID- 21848729
TI  - The influence of different sizes and types of wound fillers on wound contraction
      and tissue pressure during negative pressure wound therapy.

PMID- 21848730
TI  - Follow-up in colorectal cancer: questions to be answered.

PMID- 21848731
TI  - Commentary: MRI should not predict histopathological involved margins.

PMID- 21848732
TI  - Single-incision laparoscopic colonic surgery.
AB  - AIM: SILS is an area of growing interest in colorectal surgery. We report our
      preliminary experience of 13 consecutively selected patients undergoing colonic
      surgery using SILS. METHOD: From July 2009 to January 2010, 13 patients (five
      men) of median age 56 (23-82) years and a body mass index (BMI) of 23.5 (18-30)
      kg/m(2) underwent colonic surgery. Procedures included subtotal colectomy (1),
      ileocolic resection (2), right colectomy (4) and sigmoidectomy for benign disease
      (6). Three instruments (including camera) were introduced through a single 2.5-cm
      port (SILSTM Port Multiple Instrument Access Port; Covidien Inc., Norwalk,
      Connecticut, USA) inserted at the umbilicus. RESULTS: The median operating time
      was 150 (100-240) min, and the median size of the umbilical port incision was 32
      (25-50) mm. There was no postoperative mortality and morbidity, and the median
      hospital stay was 6 (4-10) days. The cosmetic result was judged to be excellent
      in 12 of 13 patients who felt it to be better than expected. CONCLUSION: This
      preliminary experience shows that SILS is technically feasible and safe for
      colonic resection.

PMID- 21848735
TI  - Cause or effect: what matters? How 12-month-old infants learn to categorize
      artifacts.
AB  - This paper investigates the role of cause and effect relations for infants'
      learning about artifacts. Two experiments tested whether 12-month-olds
      categorized a given set of unfamiliar artifacts according to overall similarity
      and/or according to part similarity, depending on what kind of video
      demonstration was presented before the start of the categorization task. In both
      experiments, the actions performed with objects were accompanied by interesting
      effects but the causal relation between object-structure and effects was teased
      apart. In one video demonstration (Expt 1), the experimenter used the object part
      to produce some kind of effect in a causally plausible way. In another video
      demonstration (Expt 2), the experimenter performed similar actions with the same
      objects as in Expt 1, followed by the same effects as before. Importantly,
      however, no plausible cause-effect relation was provided this time. Only infants
      participating in Expt 1 categorized the set of unfamiliar objects according to
      part similarity. This finding suggests that 12-month-olds attend to the causal
      relation between specific object parts and their functional use when categorizing
      artifacts, rather than merely associating form-characteristics with an
      interesting effect.

PMID- 21848736
TI  - What does it mean to 'live' and 'die'? A cross-linguistic analysis of parent
      child conversations in English and Indonesian.
AB  - Previous work on children's intuitive knowledge about the natural world has
      documented their difficulty in acquiring an overarching concept of biological
      life that includes plants as well as humans and non-human animals. It has also
      suggested that the acquisition of fundamental biological concepts like alive and
      die may be influenced by the language used to describe them, as evidenced by
      differences between English- and Indonesian-speaking children's performance in
      tasks involving these concepts. Here, we examine one particularly important
      source of linguistic information available to children during this acquisition
      process: everyday conversations with their parents. We take a cross-linguistic
      approach in analysing the evidence available to English- and Indonesian-speaking
      children as they acquire meanings for words corresponding to the concepts alive
      and die. Our analysis illustrates that young children acquiring English and
      Indonesian are faced with distinct problems, but that parental input in both
      languages does little to support the acquisition of broad, inclusive biological
      concepts.

PMID- 21848737
TI  - Prosocial and antisocial children's perceptions of peers' motives for prosocial
      behaviours.
AB  - This study investigated whether peer-nominated prosocial and antisocial children
      have different perceptions of the motives underlying peers' prosocial actions.
      Eighty-seven children, aged 10-12 years old, completed peer-nomination measures
      of social behaviour. On the basis of numbers of social nominations received, a
      subsample of 51 children (32 who were peer-nominated as 'prosocial', and 18 who
      were peer-nominated as 'antisocial') then recorded their perceptions of peers'
      motives for prosocial behaviours. Expressed motives were categorized
      predominantly into three categories, coinciding with Turiel's (1978) 'moral',
      'conventional', and 'personal domains'. Results indicate that children's social
      reputation is associated with the extent to which they perceive peers' prosocial
      motives as 'personal' or 'moral', with more prosocial children attributing moral
      motives, and more antisocial children attributing personal motives. Although
      traditionally Turiel's domain theory has been used to understand 'antisocial'
      children's behaviour, the current findings suggest that 'prosocial' children's
      behaviour may also be related to domains of judgment.

PMID- 21848738
TI  - Scientific reasoning in a real-world context: the effect of prior belief and
      outcome on children's hypothesis-testing strategies.
AB  - The impact of event outcome and prior belief on scientific reasoning was
      investigated within a real-world oral health context. Participants (N= 144;
      ranging from 3 to 11 years) were given hypothesis-testing tasks and asked to
      explain their answers. Participants were presented with information that was
      either consistent or inconsistent with their own beliefs. Each task consisted of
      scenarios in which the outcome was either good or bad oral health. When the
      information was belief consistent and the outcome was good, or when the
      information was belief inconsistent and the outcome was bad, children were more
      likely to choose scientifically appropriate tests of the stated hypothesis (i.e.
      manipulate only one variable). Evidence-based explanations were associated with
      scientifically appropriate choices in the good-outcome, belief-inconsistent
      scenario and the belief-consistent, bad-outcome scenario. Participants'
      performance on these tasks is explained by considering the plausibility of causal
      variables. A control of variables strategy was used to test hypotheses in cases
      in which the evidence was consistent with participants' beliefs and knowledge of
      causal mechanisms. In contrast, when the evidence was inconsistent with
      participants' beliefs, children chose to manipulate behaviours likely to lead to
      a positive health outcome. These findings demonstrate that context and prior
      knowledge interact to play an important role in children's scientific reasoning.

PMID- 21848739
TI  - Preschool children's eye-movements during pictorial recall.
AB  - We investigated eye-movements during preschool children's pictorial recall of
      seen objects. Thirteen 3- to 4-year-old children completed a perceptual encoding
      and a pictorial recall task. First, they were exposed to 16 pictorial objects,
      which were positioned in one of four distinct areas on the computer screen.
      Subsequently, they had to recall these pictorial objects from memory in order to
      respond to specific questions about visual details. We found that children spent
      more time fixating the areas in which the pictorial objects were previously
      displayed. We conclude that as early as age 3-4 years old, children show specific
      eye-movements when they recall pictorial contents of previously seen objects.

PMID- 21848740
TI  - Investigating the relationship between trait and ability emotional intelligence
      and theory of mind.
AB  - Theoretical links between emotional knowledge and theory of mind (ToM) have
      previously been proposed. This study investigates this relationship using
      measures of both ability and trait emotional intelligence (EI). Our sample
      comprised 194 children, divided into two age groups (5-7 years and 8-10 years).
      Children participated in measures of false belief understanding, advanced tests
      of ToM, ability EI and trait EI, and a standardized language assessment. For both
      age groups, we found that only ability EI was related to false belief
      understanding. Furthermore, regression analyses revealed that the understanding
      and managing branches of ability EI predicted unique variance in false belief
      understanding once controlling for age, language, and the other ability EI
      branches. Trait EI failed to display any association with false belief
      understanding. Ability and trait EI were associated with more advanced ToM tasks
      undertaken only by the older sample. These results offer support for previous
      research that has found a relationship between emotion perception and labelling
      and ToM. They also provide new knowledge: (1) higher order emotional knowledge,
      measured by ability EI, is associated with advanced ToM; and (2) emotional self
      efficacy, as measured by trait EI, is also important in advanced ToM.
      Furthermore, they provide the first account of associations between standardized
      EI measures and ToM.

PMID- 21848741
TI  - On the relationship between children's perspective taking in complex scenes and
      their spatial drawing ability.
AB  - Depicting space and volume in drawings is challenging for young children in
      particular. It has been assumed that several cognitive skills may contribute to
      children's drawing. In the present study, we investigated the relationship
      between perspective-taking skills in complex scenes and the spatial
      characteristics in drawings of 5- to 9-year-olds (N= 121). Perspective taking was
      assessed by two tasks: (a) a visual task similar to the three-mountains task, in
      which the children had to select a three-dimensional model that showed the view
      on a scene from particular perspective and (b) a spatial construction task, in
      which children had to plastically reconstruct a three-dimensional scene as it
      would appear from a new point of view. In the drawing task, the children were
      asked to depict a three-dimensional scene exactly as it looked like from their
      own point of view. Several spatial features in the drawings were coded. The
      results suggested that children's spatial drawing and their perspective-taking
      skills were related. The axes system and the spatial relations between objects in
      the drawings in particular were predicted, beyond age, by certain measures of the
      two perspective-taking tasks. The results are discussed in the light of
      particular demands that might underlay both perspective taking and spatial
      drawing.

PMID- 21848742
TI  - Positively versus negatively charged moral emotion expectancies in adolescence:
      the role of situational context and the developing moral self.
AB  - The study analyses adolescents' positively charged versus negatively charged
      moral emotion expectancies. Two hundred and five students (M= 14.83 years, SD=
      2.21) participated in an interview depicting various situations in which a moral
      norm was either regarded or transgressed. Emotion expectancies were assessed for
      specific emotions (pride, guilt) as well as for overall strength and valence. In
      addition, self-importance of moral values was measured by a questionnaire.
      Results revealed that positively charged emotion expectancies were more
      pronounced in contexts of prosocial action than in the context of moral
      transgressions, whereas the opposite was true for negatively charged emotions. At
      the same time, expectations of guilt and pride were substantially related to the
      self-importance of moral values.

PMID- 21848743
TI  - Young children's understanding of pretend crying: the effect of context.
AB  - Reasoning about another's pretend and real crying is related to ma'ny important
      social cognitive abilities (e.g., emotional understanding, appearance-reality,
      and theory of mind). This study investigated whether children aged 6 years and
      younger could distinguish between instances of pretend crying and real crying as
      presented in stories. Sixty-five Japanese children aged 4-6 years were given
      stories within two contexts (Play and Non-play). In the Play context, the
      protagonist of the story was pretending to cry or really crying during a pretend
      play activity. In the Non-play context, the protagonist was also pretending to
      cry or really crying after his/her toy had been hidden by another child. The
      children answered questions about these crying events. The results showed that
      the 4- and 5-year-olds showed significantly better understanding of pretend
      crying in the Play context compared to the Non-play context. In the Non-play
      context, they were significantly less likely to understand the cause of pretend
      crying compared to the 6-year-olds. The results suggest that the context of
      pretend play facilitates the children's understanding of pretend crying.

PMID- 21848744
TI  - Children's explanations of the intentions underlying others' behaviour.
AB  - This study investigated developmental differences in children's explanations of
      the intentions underlying the behaviours of others, including behaviours that
      conflicted with their expectations. Children aged 6-13 and adults explained the
      intentions underlying their predictions of behaviour following stories with
      ambiguous, positive, and negative cues. Children were then presented with
      experimenter-provided conflicting behaviour and explained again. Results
      indicated that with no clear cues, children and adults had optimistic
      expectations. When cues were provided, participants across development provided
      explanations consistent with positive cues, but children under age 10 were
      reluctant to provide explanations consistent with negative cues, despite good
      recall. When explaining conflicting behaviour, people may hesitate to overlook
      suspicions of negative intent sometimes even in the face of good behaviour, and
      this reluctance may increase with age. Findings suggest we may all overcome an
      optimistic bias, but children under age 10 may struggle more to do so.

PMID- 21848745
TI  - Children's perceptions and comforting strategies to infant crying: relations to
      age, sex, and empathy-related responding.
AB  - This study aimed to examine child characteristics associated with the
      understanding of and responses to infant crying. Seven hundred and twenty-four
      1st to 7th grade children (383 boys, 341 girls) were shown a picture depicting a
      crying infant, whereupon they were asked to generate the potential causes for
      infant crying along with the action responses that they might utilize to assist a
      crying baby. Self-reports of children's empathy-related responding were also
      obtained. As hypothesized, an age-related increase in the number, variety, and
      quality for causes for infant crying and strategies to help a crying infant were
      observed. Girls generated a higher mean number and variety of causes compared to
      boys. For older children (grades 4-7), dimensions of empathy-related responding,
      namely sympathy and perspective taking, were significantly associated with the
      number and variety of causes for infant crying and caregiving strategies. The
      findings support the conclusion for a developmental progression of understanding
      of facial expressions of infant crying across middle childhood.

PMID- 21848746
TI  - Comprehension and production of body part labels in 2- to 3-year-old children.
AB  - This study examined which body part labels children could (i) produce when the
      experimenter touched different locations on her own body, asking each time
      'What's this?' and (ii) comprehend by touching the correct locations on their own
      bodies in response to the experimenter asking 'Where's the [body-part label]?'.
      Seventeen children aged between 26 and 41 months, tested in a repeated measures
      procedure, were presented with 50 different body part stimuli in 200 test trials
      per child. Overall, the children produced fewer body part labels than they could
      comprehend. The accuracy of children's responses depended on (i) the location or
      extent of each body part (facial and broad body features were better known;
      joints and features in or attached to broad body parts the least well known);
      (ii) the amount of sensory (but not motor) representation each body part has in
      the human cortex; and (iii) whether a body part was commonly named by caregivers.
      These results present a precise mapping of the body parts that young children are
      able to name and locate on their own bodies in response to body part names; they
      suggest several possible determinants of lexical-semantic body knowledge and add
      to the understanding of how it develops in childhood.

PMID- 21848747
TI  - A longitudinal examination of early communicative development: evidence from a
      parent-report questionnaire.
AB  - The present research employed a longitudinal design to assess the verbal and non
      verbal communicative abilities of a sample of 104 children, using two different
      parent-report instruments: the Questionnaire for Communication and Early Language
      (QCEL) development at 12, 16, and 20 months, and the Italian adaptation of the
      MacArthur-Bates Communicative Development Inventories: Words and Gestures at 23
      months. The results supported and extended previous data about the validity of
      the QCEL, by showing that: (1) both verbal and non-verbal variables predicted the
      level of language development at 23 months; (2) children classified as at-risk
      with the QCEL had reduced vocabulary size and a lower number of sentences at 23
      months; (3) early individual differences in the use of words and gestures were
      associated with later differences in linguistic abilities. It is concluded that
      the longitudinal use of the QCEL questionnaire can provide useful information
      about language development.

PMID- 21848749
TI  - The structure of effortful control in preschoolers and its relation to
      externalizing problems.
AB  - The first aim of the present study was to examine the structure of effortful
      control. The second aim was to determine whether components of effortful control
      relate to conduct problems and hyperactivity. Effortful control was measured in 3
      year-old children (N= 89) with an observational measure, the effortful control
      battery (ECB), and a parent report, the Children's Behaviour Questionnaire (CBQ).
      Principal component analysis showed that the ECB measures five components,
      assessing two higher-order constructs, which can be labelled as Self-Control and
      Attention/Motor Control. The five scales of the CBQ appeared to measure one
      construct - a more general measure of effortful control. The components and
      constructs of the ECB as well as the scales of the CBQ were differently related
      to conduct problems and hyperactivity. Conduct problems were most strongly
      predicted by observed Delay of Gratification and parent-reported Inhibitory
      Control, whereas Hyperactivity was most strongly predicted by observed Delay of
      Gratification, and the higher-order construct Attention/Motor Control, as well as
      parent-reported Attentional Focusing and Inhibitory Control. It is important to
      keep in mind that effortful control is composed of heterogeneous components, all
      having their own unique values.

PMID- 21848748
TI  - 'We are the good guys but they are not bad'. In-group positivity and cognitive
      performance in preschoolers.
AB  - The general purpose of this study was to analyse the developmental relations
      between the early forms of ethnic attitudes, and the classification abilities of
      the young child. We designed new cognitive tasks within a detection paradigm
      adapted to preschoolers and attitudinal tasks that were presented as games in a
      computer screen. Participants were 75 majority-group children of 3, 4, and 5
      years of age. Children's preferences and positive/negative attitudes towards the
      in-group (Spaniards) and three out-groups (Latin-Americans, Africans, and Asians)
      were measured. The results showed a remarkable preference and positivity for the
      in-group, but not out-group derogation. Children's cognitive performance, to a
      greater extent than their age, was positively associated with in-group
      favouritism and positivity. On the other hand, we found some interesting
      differences and developmental changes in children's positive orientation to the
      out-groups that are discussed in the last section.

PMID- 21848750
TI  - 'In fairy tales fairies can disappear': children's reasoning about the
      characteristics of humans and fantasy figures.
AB  - Two studies assessed whether children share with adults a concept of fantasy
      figures as entities that violate causal principles. Inferences about the
      characteristics of humans and fantasy figures were elicited with a forced-choice
      questionnaire. Items from the biological, psychological, and physical domains
      pitted possible against impossible abilities; social domain items pitted
      conventional against unconventional behaviours. Older children (6-9 years) and
      adults attributed few non-human characteristics from any domain to humans and
      attributed more impossible than unconventional characteristics to fantasy
      figures. Younger children (3-5 years) attributed fewer non-human characteristics
      to humans than to fantasy figures, but attributed similar patterns of impossible
      and unconventional characteristics to humans and fantasy figures. Results are
      discussed in terms of cognitive changes between 3-5 and 6-9 years, and between 6
      9 years and adulthood, that promote awareness that impossible abilities are
      uniquely associated with fantasy.

PMID- 21848751
TI  - Pretty in pink: The early development of gender-stereotyped colour preferences.
AB  - Parents commonly dress their baby girls in pink and their baby boys in blue.
      Although there is research showing that children prefer the colour blue to other
      colours (regardless of gender), there is no evidence that girls actually have a
      special preference for the colour pink. This is the focus of the current
      investigation. In a large cross-sectional study, children aged 7 months to 5
      years were offered eight pairs of objects and asked to choose one. In every pair,
      one of the objects was always pink. By the age of 2, girls chose pink objects
      more often than boys did, and by the age of 2.5, they had a significant
      preference for the colour pink over other colours. At the same time, boys showed
      an increasing avoidance of pink. These results thus reveal that sex differences
      in young children's preference for the colour pink involves both an increasing
      attraction to pink by young girls and a growing avoidance of pink by boys.

PMID- 21848752
TI  - The architecture of high status among Finnish youth.
AB  - We tested the construct validity of a two-dimensional model of high status,
      consisting of social acceptance and perceived popularity (hereafter, acceptance
      and popularity) among Finnish children and adolescents. In addition, we
      investigated the correlates of the two forms of high status, as well as their
      relations to resource control. Participants were 563 boys and girls in grades
      four and eight, that is, aged 10-11 and 14-15. CFA and SEM models supported the
      hypothesis of acceptance and popularity representing distinct, yet associated
      constructs that have partly different correlates. Acceptance and popularity were
      most closely connected among grade four students, particularly among boys.
      Prosocial behaviour was associated with acceptance, whereas peer-valued
      characteristics (physical attractiveness, athletic ability) and aggression were
      related especially to popularity. Popularity, but not acceptance, was positively
      related to resource control.

PMID- 21848753
TI  - Self-knowledge in childhood: relations with children's imaginary companions and
      understanding of mind.
AB  - Relations between interior self-knowledge and (a) imaginary companion (IC) status
      and (b) theory of mind (ToM) abilities were investigated in a sample (N= 80) of 4
      to 7-year-olds. Interior self-knowledge was assessed in terms of the extent to
      which children acknowledged that they (rather than an adult) were the authority
      on unobservable aspects of themselves (e.g., dreaming, thinking, hunger).
      Compared with children without an IC, those who possessed a parentally
      corroborated IC ascribed less interior self-knowledge to an adult, with a trend
      for them to assign more interior self-knowledge to themselves. Children's
      interior self-knowledge judgments were not associated with their ToM performance.
      IC status was also unrelated to ToM performance. We consider how having an IC may
      provide children with opportunities to distinguish between knowledge that is
      inaccessible to an external observer and that which an external observer may
      glean without being told.

PMID- 21848754
TI  - Allergen immunotherapy: 100 years on.

PMID- 21848755
TI  - The evolution of oral immunotherapy for the treatment of peanut allergy.

PMID- 21848756
TI  - Baby--and toddler--steps toward immunotherapy for food allergy.

PMID- 21848757
TI  - Immunotherapy for allergic rhinitis.
AB  - Allergic rhinitis (AR) affects more than 20% of the population in the United
      Kingdom and western Europe and represents a major cause of morbidity that
      includes interference with usual daily activities and impairment of sleep
      quality. This guidance prepared by the Standards of Care Committee (SOCC) of the
      British Society for Allergy and Clinical Immunology (BSACI) is for the management
      of AR in patients that have failed to achieve adequate relief of symptoms despite
      treatment with intranasal corticosteroids and/or antihistamines. The guideline is
      based on evidence and is for use by both adult physicians and paediatricians
      practising allergy. During the development of these guidelines, all BSACI members
      were included in the consultation process using a web-based system. Their
      comments and suggestions were carefully considered by the SOCC. Where evidence
      was lacking, consensus was reached by the experts on the committee. Included in
      this guideline are indications and contraindications for immunotherapy, criteria
      for patient selection, the evidence for short- and long-term efficacy of
      subcutaneous and sublingual immunotherapy, and discussion on safety and the
      different modes of immunotherapy including, pre-seasonal and co-seasonal
      treatments. There are sections on children, allergen standardization, vaccines
      used in the United Kingdom, oral allergy syndrome, cost effectiveness of
      immunotherapy and practical considerations of undertaking immunotherapy including
      recommendations on who should undertake immunotherapy and dosing schedules.
      Finally, there is discussion on potential biomarkers of response to
      immunotherapy, the use of component-resolved diagnostics, novel approaches,
      alternative routes and potential areas for future research.

PMID- 21848758
TI  - Diagnosis and management of hymenoptera venom allergy: British Society for
      Allergy and Clinical Immunology (BSACI) guidelines.
AB  - This guidance for the management of patients with hymenoptera venom allergy has
      been prepared by the Standards of Care Committee (SOCC) of the British Society
      for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence
      as well as on expert opinion and is for use by both adult physicians and
      pediatricians practising allergy. During the development of these guidelines, all
      BSACI members were included in the consultation process using a web-based system.
      Their comments and suggestions were carefully considered by the SOCC. Where
      evidence was lacking, consensus was reached by the experts on the committee.
      Included in this guideline are epidemiology, risk factors, clinical features,
      diagnostic tests, natural history of hymenoptera venom allergy and guidance on
      undertaking venom immunotherapy (VIT). There are also separate sections on
      children, elevated baseline tryptase and mastocytosis and mechanisms underlying
      VIT. Finally, we have made recommendations for potential areas of future
      research.

PMID- 21848759
TI  - Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review
      and meta-analysis.
AB  - BACKGROUND: Allergic conjunctivitis (AC) is a common manifestation and represents
      an important co-morbidity of allergic rhinitis (AR). Sublingual immunotherapy
      (SLIT) is an effective and safe treatment for nasal symptoms of AR; its
      effectiveness is however less well established for ocular symptoms. OBJECTIVES:
      To evaluate the effectiveness of SLIT in reducing ocular symptoms, the need for
      ocular treatments and the threshold exposure for conjunctival immediate allergen
      sensitivity (CIAS). METHODS: We searched eight databases up to January 2010. We
      included only randomized controlled trials (RCT), double-blind and placebo
      controlled evaluating the efficacy of SLIT in patients with symptoms of allergic
      rhinoconjunctivitis (ARC) or AC. Primary outcome measures were total ocular
      symptom scores, individual ocular symptoms scores (itchy eyes, eye redness,
      watery eyes, swelling eyes), eye drops use and CIAS. Meta-analysis was undertaken
      using RevMan 5 software. RESULTS: From 811 abstracts that were screened, 109
      studies were reviewed in their full text version. Forty two trials including 3958
      participants (n=2011 SLIT and n=1947 placebo) had data suitable for inclusion in
      the meta-analysis. SLIT induced a significant reduction on both total ocular
      symptom scores (SMD: -0.41; 95%CI: -0.53 to -0.28; I(2) : 59%) and individual
      ocular symptoms scores [red (-0.33; -0.45 to -0.22), itchy (-0.31; -0.42 to 
      0.20) and watery eyes (-0.23; -0.34 to -0.11)] compared with placebo.
      Participants in the SLIT group showed an increase in the threshold dose for the
      CIAS (SMD: 0.35; 0.00-0.69). No significant reduction was observed on eye drops
      use (SMD: -0.10; -0.22 to 0.03). CONCLUSIONS AND CLINICAL RELEVANCE: SLIT is
      effective in reducing total and individual ocular symptom scores in subjects with
      ARC or conjunctivitis. No significant reduction was observed in ocular eye drops
      use.

PMID- 21848762
TI  - Gene transcription in sea otters (Enhydra lutris); development of a diagnostic
      tool for sea otter and ecosystem health.
AB  - Gene transcription analysis for diagnosing or monitoring wildlife health requires
      the ability to distinguish pathophysiological change from natural variation.
      Herein, we describe methodology for the development of quantitative real-time
      polymerase chain reaction (qPCR) assays to measure differential transcript levels
      of multiple immune function genes in the sea otter (Enhydra lutris); sea otter
      specific qPCR primer sequences for the genes of interest are defined. We
      establish a 'reference' range of transcripts for each gene in a group of
      clinically healthy captive and free-ranging sea otters. The 10 genes of interest
      represent multiple physiological systems that play a role in immuno-modulation,
      inflammation, cell protection, tumour suppression, cellular stress response,
      xenobiotic metabolizing enzymes, antioxidant enzymes and cell-cell adhesion. The
      cycle threshold (C(T)) measures for most genes were normally distributed; the
      complement cytolysis inhibitor was the exception. The relative enumeration of
      multiple gene transcripts in simple peripheral blood samples expands the
      diagnostic capability currently available to assess the health of sea otters in
      situ and provides a better understanding of the state of their environment.

PMID- 21848763
TI  - Instrumental and clinical studies of the facial skin tone and pigmentation of
      Shanghaiese women. Changes induced by age and a cosmetic whitening product.
AB  - The pigmentation patterns of facial skin of 354 healthy Chinese women aged 18-80
      years were investigated clinically and instrumentally. Chromasphere((r)) was used
      to acquire pictures from the cheeks of subjects. Facial skin tone was described
      by L* parameter from the L,a,b system as well as Individual Typology Angle (ITA).
      Results show that skin tone becomes significantly darker along the life span.
      Both size of hyper-pigmented spots and their contrast with surrounding skin were
      found increased with age. As additional study, 40 women from these 354 subjects
      were asked to apply daily a whitening cosmetic product for a 2-month period. Such
      application led to a significantly lighter skin tone, although this study was not
      vehicle controlled and we cannot exclude that the increase in L* observed was in
      some part because of cumulative effects of previously used whitening products,
      there was an association with lighter skin tone as assessed through both
      instrumental measurements and self-perception by most subjects.

PMID- 21848764
TI  - This article has been retracted and is available online only: Religion, culture
      and male involvement in the use of family planning: evidence from Enugu and
      Katsina States of Nigeria.
AB  - The following article from the International Nursing Review, 'Religion, culture
      and male involvement in the use of family planning: evidence from Enugu and
      Katsina States of Nigeria', by C. Ujuju, J. Anyanti, S.B. Adebayo, F. Muhammad,
      O. Oluigbo and A. Gofwan, published online on 6 September 2010 on Wiley Online
      Library (http://wileyonlinelibrary.com) has been retracted by agreement between
      the authors, the journal Editor in Chief, Jane J.A. Robinson and Blackwell
      Publishing Ltd. The retraction has been agreed as not all copyright permissions
      had been cleared. Jane J.A Robinson Editor International Nursing Review.

PMID- 21848765
TI  - Focussing on the wellbeing of health care workers in sub-Saharan Africa.

PMID- 21848766
TI  - Solidarity in Malta: nursing will succeed whatever the obstacles.

PMID- 21848767
TI  - Nurses fit for purpose, award and practice?

PMID- 21848771
TI  - Patient safety is not just about medication errors.

PMID- 21848773
TI  - Self-management programme for cancer patients: a literature review.
AB  - BACKGROUND: With increased cancer survivorship, cancer, in its chronic form, self
      management among cancer patients has become an international research focus. Self
      management programmes are used to guide the self-care process. Over the past 10
      years, six self-management programmes for cancer patients (Taking CHARGE, Expert
      Patients Programme, Living with Cancer Education Program, Focus Program, PRO-SELF
      Program and Oncologist-referred exercise self-management programme) were used in
      a variety of self-management studies for cancer patients. AIM: The aims of this
      paper are to describe, compare and critique these six self-management programmes
      that are commonly used to guide self-management for cancer patients, and propose
      directions for new self-management programme development among cancer patients.
      METHODS: Medline, Pubmed and Embase, Springer, Elsevier, EBSCO and ProQuest were
      searched for literatures on self-management programmes for cancer patients from
      2000 to November 2010. Search terms such as 'self-management' or 'self-care' or
      'patient education' or 'self-management' or 'self-care' or 'self-efficacy',
      'intervention' or 'program*' 'cancer' or 'carcinoma' or 'neoplasms' were used.
      RESULTS: Comparison and critique of these programmes revealed important
      limitations of cancer self-management programmes including lack of the
      facilitators' training process, failure to assess the cultural differences and
      failure to cover all of the outcome measures. CONCLUSION: Researchers and
      clinicians need to build more individualized and dynamic self-management
      programmes that parallel advances in clinical research and practice for cancer
      patients.

PMID- 21848774
TI  - A review of educational strategies to improve nurses' roles in recognizing and
      responding to deteriorating patients.
AB  - BACKGROUND: Physiological instability leading to clinical deterioration often
      precedes cardiopulmonary arrest. Nurses, who have the most frequent patient
      contact and responsibility for ongoing monitoring of patients, play a crucial
      role in recognizing and responding to clinical deterioration. The importance of
      education in supporting such a role has been addressed in numerous studies. AIM:
      This study aimed to identify nurses' educational needs and explore educational
      strategies to enhance their ability in recognizing and managing wards with
      deteriorating patients. METHODS: A literature search from databases (2000-2010)
      was undertaken to include papers that identified the educational needs of ward
      nurses and existing educational programmes related to the care of deteriorating
      patients. FINDINGS: Twenty-six papers were included in this review. Findings
      identified the educational need to empower nurses with the appropriate knowledge
      and skills in recognizing, reporting and responding to patient deterioration. The
      review of existing educational programmes and their outcomes identified valuable
      teaching information and strategies, and areas that could be improved in meeting
      nurses' educational needs. CONCLUSION: The review has highlighted important
      aspects of patient safety in clinical deterioration that could be further
      addressed by educational strategies targeting the role of ward nurses. These
      strategies include: utilizing clinical decision-making models to develop nurses'
      decision making skills; developing a standardized tool for systematic nursing
      assessment and management of clinical deterioration; incorporating training in
      clinical deterioration as a core competence of pre-registered nursing education;
      providing vital signs training to nursing assistants; and conducting more
      rigorous studies to evaluate the effectiveness of the educational programmes.

PMID- 21848776
TI  - The case for graduate entry to the United Kingdom nursing register.
AB  - AIM: The recent decision of the United Kingdom Nursing and Midwifery Council to
      make nursing a degree profession is contentious and has generated debate among
      nurses and other stakeholders. We argue why nurses need a degree to nurse and
      what the implications of making a degree in nursing obligatory at the point of
      registration will be. BACKGROUND: Nurses work at the forefront of any healthcare
      system. The complexity of their role and demands on them are increasing. To
      fulfil demands and expectations of employers, the public and the profession, and
      to be able to work collaboratively with other healthcare professions, nurses need
      critical thinking, problem-solving and decision-making skills, which can help
      them to work as independent practitioners. We argue that this can only be assured
      if the level of education for nurses is raised from diploma to degree, making
      this a prerequisite for registration as a nurse. CONCLUSIONS: The increasingly
      complex role of nurses, the changing landscape of the healthcare needs and a need
      to improve the image and status of nursing as a profession to make it an
      attractive career choice are some of the important reasons that justify nursing
      in becoming a degree-only profession.

PMID- 21848775
TI  - The nursing profession in Saudi Arabia: an overview.
AB  - AIM: The study aims to provide an overview of the nursing profession in Saudi
      Arabia, including its history, educational development, workforce and
      professional practice. BACKGROUND: Saudi Arabia is faced with a chronic shortage
      of Saudi nurses, accompanied by high rates of turnover. Expatriate nurses form a
      large proportion of the nursing workforce in Saudi healthcare facilities, with
      Saudis comprising only 29.1% of the total nursing workforce. Despite the fact
      that the proportion of Saudi nurses is very low in general, this rate is lower in
      the private health sector where local nurses comprise only 4.1% of the total.
      METHODS: Data relating to the nursing profession in Saudi Arabia were extracted
      from published literature identified through search of a range of publically
      available databases such as Medline, CINAHL, Google Scholar, Saudi health
      databases, Saudi health journals, government reports and relevant texts. Obtained
      information was evaluated for relevance and grouped on a thematic basis.
      CONCLUSION: The status of nursing in Saudi Arabia should be enhanced in order to
      make it a worthwhile career. The media should engage in helping to promote a
      positive image of the nursing profession. The education sector should reconsider
      the length of nursing training (5 years compared with 3 years in many developed
      countries) while maintaining competent and safe practice. Reducing the financial
      burden on the nursing student through provision of additional financial support
      would encourage more students. In particular, nurses should be paid a full salary
      during the intern year as currently occurs with medical students.

PMID- 21848777
TI  - Introducing traditional Chinese nursing: a review of concepts, theories and
      practices.
AB  - AIM: This paper discussed the basic concepts, theories and practices of
      traditional Chinese nursing (TCN) to enrich our understanding of relevant
      concepts and ways to contribute to human health. BACKGROUND: Advantages of TCN
      include health education based on theories and techniques of traditional Chinese
      medicine. It focuses mainly on mobilizing humans' capacity for self-adjustment
      and self-rehabilitation to make a dynamic balance between yin and yang, qi and
      blood and zang and fu. It has played a significant role in the fields of primary
      nursing, geriatric nursing, hospice, family nursing, etc., in China. METHOD:
      PubMed, CINAHL, Ovid Medline (English) and the Wang Fang (Chinese) databases were
      searched for literature on a range of keywords relating to traditional Chinese
      medicine and nursing. Forty references (13 English and 27 Chinese) were finally
      selected for review. CONCLUSION: Practices of nursing care in traditional Chinese
      medicine are based mainly on the theories of yin-yang and the five elements.
      There are two prime characteristics in the theoretical system of TCN: holism and
      nursing determination based on syndrome differentiation. The distinctive content
      include prevention, daily care of patients, dietary nursing, etc. TCN, with its
      characteristics of little damage, little pain, ease of operation and low cost, is
      appropriately used in primary health care in China. By combining Western and
      Eastern philosophies and approaches to nursing, life phenomena can be better
      understood, and more ways to promote health can be exploited. Scientists are
      beginning to use Western research methods to establish effectiveness. Many common
      interventions would not, however, be considered safe in Western nursing practice
      without more evidence and consideration of health and safety issues.

PMID- 21848778
TI  - Chronic and non-communicable diseases: a critical challenge for nurses globally.
AB  - BACKGROUND: Chronic and non-communicable diseases (NCDs) are a growing and
      enormous challenge that faces countries across the world. Low- and middle-income
      countries are disproportionately affected. CONTRIBUTORY FACTORS: Three risk
      factors--tobacco use, poor diet (including excessive alcohol intake) and lack of
      physical activity--contribute to four major chronic diseases--cardiovascular,
      chronic obstructive pulmonary disease, diabetes and some cancers, which are
      responsible for over 50% of deaths worldwide. POTENTIAL SOLUTIONS: International
      governmental and non-governmental agencies are becoming increasingly concerned
      and active. Nurses across the world are well positioned to play a significant
      role and work with a wide range of people involved in the prevention and
      management of these chronic diseases.

PMID- 21848779
TI  - Experiences of the great East Japan earthquake March 2011.
AB  - Written just 5 weeks after the Great East Japan Earthquake of 11 March 2011, this
      personal account provides new lessons for disaster nursing. Expecting aid to
      reach a major widespread disaster area within 3 days is optimistic, and survivors
      may have to exist on extremely limited resources for very much longer. Even in a
      country as well prepared as Japan, material and human resources after March 11
      were stretched to their limits. The nuclear accident dimension created great
      anxiety especially among pregnant women and mothers of young children.

PMID- 21848780
TI  - Development and evaluation of 'disaster preparedness' educational programme for
      pregnant women.
AB  - PURPOSE: The objective of this study is the development and evaluation of the
      usability of an educational programme that teaches disaster preparedness to
      pregnant women. METHODS: This intervention study examined an intervention group
      that attended an educational programme and a control group that did not. The
      subjects were pregnant women in their second trimester. The programme was
      developed with prior studies and evaluated by self-administered questionnaires
      that asked about disaster preparedness. The questionnaire was administered twice
      to the participants in both groups: to the intervention group just before the
      childbirth class and 1 month after the class, and to the control group at the
      time of their maternity examination and 1 month afterwards. Two hundred twenty
      six members of the intervention group and 262 members of the control group
      responded to both questionnaires. Of these, 99 of the intervention group and 104
      of the control group were primiparous without disaster experience, and the
      programme was evaluated by comparing these two groups. Effects due to the
      disaster experience were also analysed within the intervention group. RESULTS:
      Among primiparous without disaster experience, an intervention effect was found
      in items concerning awareness modification (five of six items) and behaviour
      modification (three of seven items). The intervention effect was particularly
      pronounced in a comparison of primiparous without disaster experience.
      CONCLUSIONS: An intervention effect was found among the pregnant women who took
      the programme. In particular, it was statistically significant among primiparous
      without disaster experience, which suggests that the programme should be shaped
      to reflect this subject demographic.

PMID- 21848781
TI  - The effectiveness of a disaster training programme for healthcare workers in
      Greece.
AB  - BACKGROUND: Recent natural disasters have made disaster training a public
      priority. Multiple methods of disaster preparedness training have been
      established in hospitals worldwide. Nevertheless, researchers have not yet
      discovered the most effective method for training hospital personnel in the area
      of disaster preparedness. AIM: The aim of this study is to test the hypothesis
      that a brief educational intervention would improve hospital staff knowledge
      about the hospital disaster plan and procedures. METHODS: A quasi-experimental
      design was used. The intervention group included 56 professionals and the
      comparison group included 35 professionals in Greece. The intervention group
      attended a 5-h course that addressed the basic principles of hospital disaster
      management. A structured questionnaire was used to estimate the participants'
      changes in knowledge. Repeated measures analysis of variance (ANOVA), t-test, one
      way ANOVA and chi-square test were used to analyse the data. RESULTS: The
      intervention resulted in a significant improvement in knowledge. The mean score
      was significantly higher immediately after the intervention programme [86;
      standard error (SE): 2] than before (44.5; SE: 1.7) (P<0.001). The mean score 1
      month later was significantly lower (77.2; SE: 2.3) than that immediately after
      the intervention programme (P<0.001), but significantly higher than the mean
      score before the intervention programme (P<0.001). Participants in the control
      group achieved a score of 40 (SE: 2.4), which was significantly lower than the
      scores of the intervention group after the course (P<0.001). CONCLUSION: The
      disaster training course had a great benefit for the participants. This study
      suggests that a brief educational intervention is beneficial, but more must be
      done.

PMID- 21848782
TI  - Selecting examinable nursing core competencies: a Delphi project.
AB  - AIM: To establish a set of core competencies that could be practically examined
      in a pre-registration practical examination for Indonesian candidates completing
      their pre-service education. BACKGROUND: Indonesia is planning to institute a
      register for nurses to ensure a minimum standard of safe practice for new nurses
      completing their pre-service education. A proposed route to registration includes
      the practical examination of a minimum set of core competencies. This Delphi
      project aimed to reduce 192 existing standard competencies to an examinable group
      of 12 core competences that all nurses registering in Indonesia must meet.
      METHOD: A modified Delphi method was used by 12 expert Indonesian nurses and a
      facilitator to determine which standard competencies should be considered core.
      RESULTS: Five Delphi rounds were used. One hundred and ninety-two standard
      competencies were reduced to a core set of 12. Selected competencies are
      assessable in a practical examination and can be used to determine a minimum
      level of safe practice for all nurses seeking to register at the completion of
      their pre-service education. CONCLUSION: The expert panel met the project aim and
      provided a set of examinable competencies/activities that they consider will
      demonstrate the fundamental safety of new registered nurses. The subsequent
      responsibility for setting up a register for nurses in Indonesia now rests with
      the Indonesian Ministry of Health. The Indonesian National Nursing Association is
      working with the Ministry of Health to determine the route and criteria for
      registration in order to establish a common level of competence for nurses across
      the country exiting their pre-service education.

PMID- 21848783
TI  - Commuting patterns among Italian nurses: a cross-sectional study.
AB  - Commuting is an additional burden that affects working stress, reduces leisure
      time and raises the risk of accidents. Little data are available about nurses'
      commuting patterns or the impact of commuting on their lives. OBJECTIVES: The
      study aims to describe commuting patterns among Italian nurses and to explore
      possible associations with nurses' intention to change job. METHODS: This is a
      cross-sectional study carried out in central Italy. Nurses were invited to
      participate through a variety of public measures. Those participating completed
      an online questionnaire available on a website established for this specific
      purpose. RESULTS: Five hundred sixty-five nurses participated. The mean distance
      covered every day to go to work and back home is 30.8 km. A total of 43.3% of
      nurses cover 25 km or more every day to work; 5.7% cover 100 km or more. The mean
      time spent in commuting is 52.9 min daily. Furthermore, 14.5% of nurses spend
      every month commuting a time equal to or longer than the working time of 1 week.
      The mean monthly expenditure is 87.30 Euro (6% of mean salary). Nurses younger
      than 30 cover longer distances (P=0.0006), spend more time (P=0.001) and have
      higher expenditure (P=0.003) than their older colleagues. Willingness to change
      job seems associated with the use of public means of transportation (P=0.04).
      Nurses from the population under study cover longer distances, spend longer time
      in daily commuting and have higher monthly costs than the rest of the Italian
      workers' population. CONCLUSIONS: Travelling to work represents a non-negligible
      burden for nurses, particularly for younger nurses. Nurses seem to have lesser
      opportunities to rest and to recover energies than other workers. The Italian
      nurses' recruiting system may have a role in explaining our data. Further studies
      are needed to investigate the impact of nurses' commuting on the healthcare
      system.

PMID- 21848784
TI  - A survey of psychiatrists' and registered nurses' levels of mental health
      literacy in a Chinese general hospital.
AB  - BACKGROUND: Mental health literacy (MHL) is the term used to describe people's
      knowledge and beliefs about mental disorders which aid in the recognition,
      management or the prevention of illness. Health professionals' levels of MHL will
      shape the therapeutic relationship in which they work in partnership with
      patients. Studies have been conducted in Australia and Singapore to determine
      levels of MHL among members of the general public and health professionals. To
      date, no such studies have been published in Chinese populations. AIM: The study
      aims to compare levels of MHL between registered nurses and psychiatrists in a
      Chinese general hospital. The paper reports participants' diagnosis and beliefs
      about interventions used to manage depression and schizophrenia. METHODS: A
      descriptive cross-sectional survey was undertaken among a group of psychiatrists
      and registered nurses in the psychiatric department of one large teaching
      hospital in China (n=70). Participants completed the survey by rating written
      vignettes related to depression and schizophrenia. RESULTS: The psychiatrists
      were highly accurate in correctly diagnosing both depression and schizophrenia;
      the registered nurses were less so for diagnosing depression. In terms of
      treatment options, the two groups reached a broad agreement on beliefs about the
      use of mental health interventions, but differed significantly in the use of some
      specific mental health interventions. CONCLUSIONS: This study provides
      preliminary information about levels of MHL among Chinese mental health
      professionals and describes their attitudes towards the helpfulness of
      interventions used to restore mental health and well-being. Future large-scale
      studies are required to identify factors that influence beliefs about the use of
      mental health interventions. The findings have implications for further education
      of registered nurses in the specialization of mental health nursing in China.

PMID- 21848785
TI  - Commanding insights in a survey of psychiatrists' and registered nurses' levels
      of mental health literacy in a Chinese general hospital.

PMID- 21848786
TI  - Breastfeeding knowledge and attitudes among Egyptian baccalaureate students.
AB  - AIM: To assess the breastfeeding knowledge, attitudes and perceived adequacy of
      breastfeeding education among baccalaureate nursing students in Cairo, Egypt.
      Self-confidence to provide breastfeeding support for mothers was also
      investigated. BACKGROUND: Nurses play a crucial role in promoting breastfeeding.
      Studies in Western countries have found inadequate breastfeeding knowledge among
      undergraduate nursing students. No published literature about breastfeeding
      knowledge and attitudes among nursing students in Egypt was found. METHOD: An
      exploratory descriptive study used a sample of 110 baccalaureate nursing students
      from Cairo, Egypt. Students who had completed maternal/child nursing didactic and
      clinical courses were eligible to participate. Ninety two (83.6%) students
      completed the survey during spring 2009. We used a Breastfeeding Knowledge
      Questionnaire adapted from Brodribb et al. to measure breastfeeding knowledge and
      the Iowa Infant Feeding Attitude Scale to test students' breastfeeding attitudes.
      RESULTS: Students' age ranged from 18 to 21 years with a mean of 19.5+/-1.2 with
      75% being female. The mean breastfeeding knowledge score was 12.41 points out of
      24, which represents 52% of the total score. The attitudes mean score was 3.13+/
      0.64. There was a significant relationship between the students' knowledge and
      attitudes scores (r=0.236, P=0.011). Eighty per cent of the students reported
      that they received adequate breastfeeding knowledge and skills in their nursing
      programme, and 70% were confident in their ability to provide breastfeeding
      support. CONCLUSION: Results revealed weak breastfeeding knowledge scores among
      students and neutral breastfeeding attitudes. Strategies to improve breastfeeding
      education in nursing curriculum focusing on breastfeeding management skills are
      warranted.

PMID- 21848787
TI  - Practices for caring in nursing: Brazilian research groups.
AB  - BACKGROUND: The present study considers the production of knowledge and the
      interactions in the environment of research and their relationships in the system
      of caring in nursing and health. AIM: To elaborate a theoretical model of the
      organization of the practices used for caring, based on the experiences made by
      the research groups of administration and management in nursing, in Brazil.
      METHODS: The study is based on grounded theory. Twelve leaders of research
      groups, working as professors in public universities in the south and the south
      east of Brazil, distributed in sample groups, were interviewed. FINDINGS: The
      core phenomenon 'research groups of administration and management in nursing:
      arrangements and interactions in the system of caring in nursing' was derived
      from the categories: conceptual bases and contexts of the research groups;
      experiencing interactions in the research groups; functionality of the research
      groups; and outputs of the research groups. The research groups are integrated in
      the system of caring in nursing. CONCLUSIONS: The activities of the Brazilian
      administration and management in nursing research groups are process oriented and
      in a process of constant renovation, socially relevant, operate in a complex
      scenario and contribute to the advancement of the organizations of the system of
      caring in nursing through strengthening the connection among academia, service
      and community.

PMID- 21848788
TI  - Capacity development for community health nurses in Pakistan: the assistant
      manager role.
AB  - BACKGROUND: Community health nurses (CHNs), as leaders in developing countries,
      can promote successful outcomes in meeting the targets of the Millennium
      Development Goals. A community-based organization in Pakistan is striving to
      achieve the goals of maternal and child health through the development of the
      assistant manager role for community health nursing. PURPOSE: The purpose of this
      study was to assess the perception of the role of the CHN assistant manager, with
      the goal of strengthening that role. METHODS: This interpretive, qualitative
      study included 13 participants already familiar with CHNs in Pakistan.
      Interviewing was utilized to explore perceptions of the assistant manager role
      and to uncover challenges currently existing within this new role. FINDINGS:
      Content analysis revealed the following themes: 'role perceptions', 'expectations
      of the role' and 'collaboration with other community healthcare providers'.
      CONCLUSION: Changes to the role are necessary including increased education of
      the assistant manager CHNs and preparing administration to work with the
      assistant mangers for effective leadership.

PMID- 21848789
TI  - Strategies to develop the nursing process and nursing care plans in the health
      system in Bolivia.
AB  - BACKGROUND: Care plans provide guidelines to offer all patients the same quality
      assistance. Care plans constitute a base where every stage of the nursing process
      can be recorded, which will save time when handling documentation. Bolivian
      nurses are very keen to participate in this global trend in order to grasp the
      opportunity offered by the international cooperation programmes carried out
      between Spain and South America. AIMS: To identify obstacles and enablers
      encountered when implementing the nursing process and to set clear strategies and
      actions so as to develop the nursing process and care plans in Santa Cruz
      department (Bolivia) both in hospitals and universities. METHODS: The
      participatory action research was conducted between the Autonomous University of
      Gabriel Rene Moreno (Bolivia) and the University of Almeria (Spain). The
      procedure for data collection included meetings with key informants, interviews,
      observation and workshops. Data were analysed using the constant comparison and
      categorized by common themes. RESULTS: Lack of time and instruments, shortage of
      resources and the need for continuous training came up as obstacles, whereas
      enablers were the nurses' involvement, the university-hospital coordination and
      the support given by institutions. Actions taken were the creation of a care plan
      unit, the implementation of a training programme, design of instruments and
      meetings held with authorities and institutional representatives. CONCLUSIONS:
      Conducting action research schemes within international cooperation programmes
      signifies an excellent opportunity for the nursing system in less-developed
      countries to be included in international plans with the aim of standardizing the
      nursing practice.

PMID- 21848790
TI  - The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI)
      resistance in patients kept on a virologically failing regimen containing an
      NNRTI*.
AB  - BACKGROUND: Virological failure of first-generation nonnucleoside reverse
      transcriptase inhibitors (NNRTIs) can compromise the efficacy of etravirine as a
      result of the accumulation of NNRTI resistance mutations. How quickly NNRTI
      resistance accumulates in patients with a delayed switch from nevirapine or
      efavirenz despite virological failure, when these drugs are used as a component
      of combination antiretroviral therapy (cART), remains unclear. METHODS: The rate
      of NNRTI resistance accumulation was estimated in patients in EuroSIDA with at
      least two available genotypic resistance tests (GRTs), provided that (1) the date
      of the first GRT (t0) was after the date of the first virological failure (VF) of
      an NNRTI, and (2) patients were receiving an NNRTI and HIV RNA was >500 HIV-1 RNA
      copies/mL in all measurements between GRTs. RESULTS: A total of 227 patients were
      included in the study, contributing 467 GRT pairs. At baseline-t0, a median of 3
      months after VF, 66% of patients had at least one NNRTI mutation: 103N (34%),
      181C (22%) and 190A (20%) were the most common mutations. Overall, 180 additional
      NNRTI mutations were found to have accumulated over 295 years [1 new/1.6 years;
      95% confidence interval (CI) 1.5-1.8]. The rate of accumulation was faster in the
      first 6 months from VF (1 new/1.1 years), and slower in patients exposed to
      nevirapine vs. those receiving efavirenz [relative risk (RR) 0.66; 95% CI 0.46
      0.95; P=0.03]. CONCLUSIONS: There is an initial phase of rapid accumulation of
      NNRTI mutations close to the time of VF followed by a phase of slower
      accumulation. We predict that it should take approximately one year of exposure
      to a virologically failing first-generation NNRTI-based cART regimen to reduce
      etravirine activity from fully susceptible to intermediate resistant, and
      possibly longer in patients kept on a failing nevirapine-containing regimen.

PMID- 21848791
TI  - Editorial comment to factors predicting continence recovery 1 month after radical
      prostatectomy: results of a multicenter survey.

PMID- 21848792
TI  - Increased expression of CYP17 and CYP11B1 in subclinical Cushing's syndrome due
      to adrenal adenomas.
AB  - OBJECTIVES: To determine whether steroidogenic enzyme expression is associated
      with the steroid secretory pattern of subclinical Cushing's syndrome (SCS) by
      investigating the mRNA and protein expression of CYP17 and CYP11B1 in SCS
      adenomas, normal adrenal cortices (NA), non-functional adrenal adenomas (NFA) and
      cortisol-producing adenomas (CPA). METHODS: Total RNA and protein were extracted
      from 20 CPA, six SCS, 15 NFA, and eight NA. Real-time quantitative polymerase
      chain reaction (PCR) and western blotting analysis were performed to determine
      the mRNA and protein expression of CYP17 and CYP11B1 in different tissues. The
      expression of CYP17 and CYP11B1 in the adrenocortical tumors was compared
      expression in NA. RESULTS: Expression of both CYP11B1 and CYP17 mRNA and protein
      was detected in all samples tested. The expression of CYP11B1 mRNA and protein
      was significantly higher in the CPA group than in the other groups and was
      slightly higher in SCS samples compared with NA and NFA samples (all P < 0.05).
      There was no significant difference in CYP11B1 mRNA and protein expression
      between NA and NFA samples (P > 0.05). The expression of CYP17 mRNA and protein
      in different tissues was similar to that of CYP11B1. Neither CYP11B1 nor CYP17
      mRNA and protein expression was correlated with plasma cortisol or
      adrenocorticotrophin levels (all P > 0.05). CONCLUSIONS: In conclusion, CYP11B1
      and CYP17 are overexpressed in subclinical CPA and their overexpression accounts
      for the increased production of cortisol that is characteristic of CPA.

PMID- 21848793
TI  - Early initiation of cinacalcet for the treatment of secondary hyperparathyroidism
      in hemodialysis patients: a three-year clinical experience.
AB  - Despite the availability of standard therapy (vitamin D sterols and phosphate
      binders) for the treatment of secondary hyperparathyroidism (SHPT) in
      hemodialyzed (HD) patients, a significant percentage of patients still fail to
      achieve targets recommended by the Kidney Disease Outcomes Quality Initiative
      (K/DOQI) of the National Kidney Foundation for parathyroid hormone (PTH),
      calcium, and phosphorus. The calcimimetic cinacalcet (CN) has been shown to be an
      effective treatment for SHPT, significantly reducing serum PTH while
      simultaneously lowering calcium, phosphorus, and calcium-phosphorus product
      levels, thus increasing the proportion of patients achieving the K/DOQI targets
      for bone mineral parameters. The aim of this study was to evaluate if early
      treatment with CN had beneficial effects in HD patients with mild-to-moderate
      SHPT in whom conventional treatments had failed to achieve NKF-K/DOQI targets for
      PTH, serum-corrected calcium, and phosphorus while minimizing the risk of
      paradoxical hypercalcemia and/or hyperphosphatemia. Clinical practice data were
      collected monthly, starting from 6 months prior to, and up to 36 months after,
      the start of CN therapy. CN was started at a dose of 30 mg daily or every other
      day, and titrated thereafter to achieve intact PTH (iPTH) <300 pg/mL. The dose of
      concomitant vitamin D and phosphate binders were also adjusted in order to
      achieve K/DOQI targets. Data from 32 patients were collected, 28 of whom had been
      treated with CN for at least 36 months at the time of data analysis. At baseline,
      patients had serum iPTH >300 pg/mL (570 +/- 295 pg/mL) and/or serum-corrected
      calcium >9.5 mg/dL. CN induced significant decreases in iPTH, calcium, and
      calcium-phosphorus product with respect to baseline levels. The percentage of
      patients within K/DOQI target levels at baseline, 12, 24, and 36 months was 0,
      81.2, 83.3, and 86.2% for iPTH; 34.4, 65.6, 86.6, and 89.6% for serum-corrected
      calcium; 40.6, 56.2, 69.6, and 72.4% for phosphorus; and 37.5, 62.5, 80, and
      82.7% for calcium-phosphorus product. The mean dose of CN at the end of the
      observation period was 38 mg/day. The mean dose of concomitant medication
      (calcitriol, Al-containing phosphate binders, and sevelamer) decreased from
      baseline to 36 months. Early treatment with CN in HD patients with SHPT increases
      the proportion of patients achieving and maintaining K/DOQI targets with a low
      dose of CN (38 mg/day). These results suggest that the metabolic control obtained
      with low-dose CN administered early in the course of SHPT can be maintained or
      increased over time.

PMID- 21848794
TI  - Distinct proteomic profiles characterise non-erosive from erosive reflux disease.
AB  - BACKGROUND: Erosive reflux disease (ERD) and non-erosive reflux disease (NERD)
      are often regarded as part of the spectrum of the same disease. AIM: To elucidate
      molecular features that characterise NERD and ERD at the protein level. METHODS:
      A total of 56 consecutive subjects were enrolled: 10 healthy subjects, 24 with
      NERD and 22 with ERD. Eight specimens were taken from macroscopically normal
      mucosa at 5 cm of gastro-oesophageal junction. Four were processed for the
      proteins extraction and four for evaluation using haematoxylin-eosin and
      immunohistochemistry. We used shotgun proteomics to identify tentative disease
      molecular features for ERD or NERD. Candidate distinctive proteins were verified
      using immunohistochemistry. RESULTS: Shotgun proteomics analysis revealed 33
      differentially expressed proteins in NERD vs. ERD samples, involved in cellular
      proliferation, keratinisation, stress responses and sugar metabolism. Based on a
      gene ontology meta-analysis, seven of them were further analysed using Western
      blotting (WB) and four also using immunohistochemistry. We identified novel
      candidate disease molecular features for GERD and few distinctive proteins to
      discriminate NERD and ERD. In particular, Transitional Endoplasmic Reticulum
      ATPase (TER ATPase), GAPDH, Alpha 1 Acid Glycoprotein 1, Annexin A1, Calmodulin
      and 14-3-3 proteins were confirmed at WB analysis. CONCLUSIONS: Non-erosive
      reflux disease and ERD are distinct disease entities at the protein level. This
      study proposes an array of candidate biomarkers possibly useful to discriminate
      between NERD and ERD.

PMID- 21848795
TI  - Epidemiology of functional constipation and comparison with constipation
      predominant irritable bowel syndrome: the Systematic Investigation of
      Gastrointestinal Diseases in China (SILC).
AB  - BACKGROUND: The epidemiology and effects of functional constipation (FC) on
      Chinese people remain unclear. AIM: To investigate the epidemiology of FC and its
      distinction from constipation-predominant irritable bowel syndrome (IBS-C) in
      China. METHODS: A cross-sectional survey was conducted in a representative adult
      Chinese population (n = 16,078), which was selected from five regions using
      randomised, stratified, multistage sampling methodology. All respondents
      completed the modified Rome II questionnaire; 20% were asked to complete the 36
      item Short Form (SF-36) and the Epworth Sleepiness Scale (ESS). RESULTS: Overall,
      948 respondents (6%) had FC and FC was more prevalent in women than in men (8%
      vs. 4%, P < 0.001). Straining and hard stools were the two most frequent
      symptoms. FC was associated significantly with dyspepsia and abdominal bloating.
      All SF-36 domain scores were lower for respondents with FC than for those
      without. The prevalence of clinically meaningful daytime sleepiness was
      significantly higher in respondents with FC than in those without (22% vs. 14%, P
      = 0.003). Respondents with FC were more likely to strain, but less likely to have
      a feeling of incomplete emptying after a bowel movement than those with IBS-C.
      Respondents with IBS-C experienced similar demographics, quality of life and
      daytime sleepiness to those with FC. CONCLUSIONS: The prevalence of FC in China
      is substantially lower than that in Western countries. FC has negative effects on
      quality of life and daytime sleepiness. The demographics and burden of illness
      are similar between FC and IBS-C, although the clinical symptoms are somewhat
      different.

PMID- 21848796
TI  - No difference in mortality in undetected coeliac disease compared with the
      general population: a UK cohort study.
AB  - BACKGROUND: Studies of mortality in undetected coeliac disease compared with the
      general population give contradictory findings, suggesting it is either increased
      fourfold compared with the general population or not at all. AIM: To establish
      all-cause and cause-specific mortality in undiagnosed coeliac disease, identified
      by anti-endomysial antibody (EMA) positivity, in the Cambridge GP Health Survey
      cohort. METHOD: This cohort was recruited in 1990 from the general population
      aged 45-76 years. All deaths were ascertained from the Office for National
      Statistics. Mortality rates were calculated per 1000 person years and adjusted
      for age, gender, smoking and socioeconomic group using multivariate Cox
      regression to estimate hazard ratios (HR) and 95% confidence intervals (CI).
      RESULTS: There were 117,914 patient years of follow-up (median 16.8 years) from
      7527 participants. Eighty-seven had undetected coeliac disease, their all-cause
      mortality rate was 9.4 per 1000 person years (95% CI 5.4-16.1) compared with 12.7
      (95% CI 12.1-13.4) in EMA-negative participants. The adjusted all-cause mortality
      HR was 0.98 (95% CI 0.57-1.69). Death due to cancer and circulatory diseases was
      not increased, adjusted HR were 1.27 (95% CI 0.57-2.85) and 1.39 (95% CI 0.66
      2.92) respectively. CONCLUSIONS: We observed no excess overall mortality in
      people aged over 45 years with undetected coeliac disease compared with the
      general population, nor any increase in deaths related to circulatory disease or
      cancer. Our findings do not support screening the general population aged over 45
      years, for coeliac disease for the purpose of improving life expectancy.

PMID- 21848797
TI  - Randomised clinical trial: rifaximin improves health-related quality of life in
      cirrhotic patients with hepatic encephalopathy - a double-blind placebo
      controlled study.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is a brain disorder that often results
      from cirrhosis due to viral hepatitis, metabolic and alcohol-related liver
      disease, and is characterised by cognitive, psychiatric and motor impairments.
      Recurrent bouts of overt HE negatively impact daily functioning and quality of
      life. AIM: To evaluate the effect of rifaximin on health-related quality of life
      (HRQL) in cirrhotic patients with HE. METHODS: Patients with cirrhosis in
      remission from HE (Conn score = 0 or 1) and a documented history of recurrent HE
      episodes (>=2 within 6 months of screening) were randomised to rifaximin 550 mg
      twice daily (N = 101) or placebo (N = 118) for 6 months. Concomitant lactulose
      was permitted during the study. The Chronic Liver Disease Questionnaire (CLDQ)
      was administered every 4 weeks, and time for occurrence of HE breakthrough was
      recorded. A longitudinal analysis using time-weighted averages of the CLDQ scores
      normalised by days on study therapy was used to evaluate the effect of treatment
      on HRQL, and between HE outcomes (HE recurrence, yes/no) irrespective of
      treatment. RESULTS: The time-weighted averages of the overall CLDQ score and each
      domain score were significantly higher in the rifaximin group vs. placebo (P
      values ranged from 0.0087 to 0.0436); and were significantly lower in patients
      who experienced HE breakthrough compared to those who remained in remission (P
      values were <0.0001). CONCLUSION: Rifaximin significantly improved HRQL in
      patients with cirrhosis and recurrent hepatic encephalopathy. A lower HRQL may
      predict recurrence of hepatic encephalopathy.

PMID- 21848798
TI  - MiraLAX vs. Golytely: is there a significant difference in the adenoma detection
      rate?
AB  - BACKGROUND: In recent clinical trials (RCT) of bowel preparation, Golytely was
      more efficacious than MiraLAX. We hypothesised that there is a difference in
      adenoma detection between Golytely and MiraLAX. AIMS: To compare the adenoma
      detection rate (ADR) between these bowel preparations, and to identify
      independent predictors of bowel preparation quality and adenoma detection.
      METHODS: This was a post hoc analysis of an RCT that assessed efficacy and
      patient tolerability of Golytely vs. MiraLAX/Gatorade in average risk screening
      colonoscopy patients. Bowel preparation quality was measured with the Boston
      Bowel Preparation Scale (BBPS). An excellent/good equivalent BBPS score was
      defined as >= 7. Polyp pathology review was performed. ADR was defined as the
      proportion of colonoscopies with an adenoma. Univariate and multivariate analyses
      were conducted. RESULTS: One hundred and ninety patients were prospectively
      enrolled (87 MiraLAX, 103 Golytely). Golytely had a higher rate of a BBPS score
      >= 7 (82.5% vs. MiraLAX 67.8%, P=0.02). The ADR in the Golytely cohort was 26.2%
      (27/103), and was 16.1% (14/87) for MiraLAX (P = 0.091). On multivariate
      analyses, Golytely was 2.13 * more likely to be associated with a BBPS >= 7 (95%
      CI 1.05-4.32, P = 0.04) and 2.28 * more likely to be associated with adenoma
      detection (95% CI 1.05-4.98, P = 0.04) than MiraLAX. CONCLUSIONS: Golytely was
      more efficacious than MiraLAX in bowel cleansing, and was independently
      associated with both bowel prep quality (BBPS >= 7) and higher adenoma detection.
      Golytely should be used as first line for bowel prep for colonoscopy. Studies
      with larger populations are needed to confirm these results.

PMID- 21848799
TI  - Randomised clinical trial: the burden of illness of uninvestigated dyspepsia
      before and after treatment with esomeprazole--results from the STARS II study.
AB  - BACKGROUND: Patients with dyspepsia often experience troublesome symptoms. AIM:
      To assess the burden of uninvestigated dyspepsia (symptoms, health-related
      quality of life [HRQL] and work productivity) before and after 8 weeks'
      esomeprazole treatment. METHODS: Patients (n=1250) with uninvestigated dyspepsia
      (no endoscopy within 6 months and <= 2 endoscopies within 10 years) underwent a 1
      week esomeprazole acid-suppression test before randomisation to 7 weeks'
      esomeprazole or placebo. The Reflux Disease Questionnaire (RDQ), Quality of Life
      in Reflux and Dyspepsia (QOLRAD) and Work Productivity and Activity Impairment
      (WPAI) questionnaires were completed at baseline (1-week off-treatment) and 8
      weeks. WPAI results were further analysed among patients who responded to the
      acid-suppression test. RESULTS: The highest baseline symptom score was for the
      RDQ dyspepsia domain, and the highest disease burden was for QOLRAD vitality and
      food/drink problems. After 8 weeks, significant improvements vs. placebo were
      observed for all RDQ and QOLRAD domains. The sub-population of acid-suppression
      test responders, but not the total WPAI population, had a significant work
      productivity improvement vs. placebo. CONCLUSIONS: Uninvestigated dyspepsia is
      associated with high symptom load and impacts on HRQL and work productivity.
      Esomeprazole improves HRQL among such patients, and improves work productivity
      among 1-week acid-suppression trial responders. ClinicalTrials.gov identifier:
      NCT00251992.

PMID- 21848800
TI  - N-linked glycosylation in Archaea: two paths to the same glycan.
AB  - N-linked protein glycosylation occurs in all three branches of life, eukaryotes,
      bacteria and archaea. The simplest system is that of the bacterium, Campylobacter
      jejuni, in which a heptasaccharide glycan is added to multiple proteins from a
      single lipid carrier molecule. In the eukaryotic system a conserved
      tetradecasaccharide modification is first added to target proteins, but is then
      modified by trimming and addition of other glycans from additional carrier
      molecules resulting in a diverse array of glycans of distinct functionality. In
      the halophilic Archaea from the Dead Sea, Haloferax volcanii, the surface array
      or S-layer protein is glycosylated with a pentasaccharide. This glycan is
      synthesized from two separate carrier molecules, one that carries a
      tetrasaccharide and another that carries the terminal mannose, in a process that
      is analogous to that of eukaryotes. In this issue of Molecular Microbiology the
      glycosylation of the S-layer of another halophilic Archaea from the Dead Sea,
      Haloarcula marismortui is characterized (Calo et al., 2011). This S-layer is
      glycosylated with the same pentasaccharide as that of Hfx.  volcanii, but the
      intact pentasaccharide is synthesized on a single carrier molecule in Har.
      marismortui in a process that more closely resembles that of the bacterial N
      linked system.

PMID- 21848801
TI  - Severe fatigue in narcolepsy with cataplexy.
AB  - Excessive daytime sleepiness (EDS) is the core symptom of narcolepsy. However,
      there have been indications that fatigue - which should be separated from EDS--is
      also a frequent complaint. We determined the prevalence of severe fatigue in a
      group of narcolepsy patients and its relation with excessive daytime sleepiness,
      psychological distress, functional impairment and quality of life. We included 80
      patients fulfilling the International Classification of Sleep Disorders (ICSD)-2
      diagnostic criteria of narcolepsy with cataplexy. Fatigue was measured using the
      Checklist Individual Strength (CIS). In addition psychological distress,
      including symptoms of depression, functional impairment and quality of life, were
      assessed. Comparisons were made between patients with (CIS-fatigue score >= 35)
      and without severe experienced fatigue. Fifty patients (62.5%) reported severe
      fatigue. There were no sex or age differences between patients with and without
      severe fatigue. Both fatigued and non-fatigued patients had the same amount of
      daytime sleepiness (Epworth Sleepiness Score 14.3 +/- 4.2 versus 13.1 +/- 4.4, P
      = 0.22), confirming the separation between sleepiness and fatigue. Interestingly,
      fatigued patients more often used stimulant medication (64% versus 40%, P =
      0.02). Severe fatigue was associated with a significantly increased functional
      impairment, increased depressive symptoms and a lowered general quality of life.
      In conclusion, a majority of patients with narcolepsy suffer from severe fatigue,
      which can be distinguished from daytime sleepiness, and results in severe
      functional impairment.

PMID- 21848802
TI  - Experience-dependent induction of hypnagogic images during daytime naps: a
      combined behavioural and EEG study.
AB  - This study characterizes hypnagogic hallucinations reported during a
      polygraphically recorded 90-min daytime nap following or preceding practice of
      the computer game Tetris. In the experimental group (N = 16), participants played
      Tetris in the morning for 2 h during three consecutive days, while in a first
      control group (N = 13, controlling the effect of experience) participants did not
      play any game, and in a second control group (N = 14, controlling the effect of
      anticipation) participants played Tetris after the nap. During afternoon naps,
      participants were repetitively awakened 15, 45, 75, 120 or 180 s after the onset
      of S1, and were asked to report their mental content. Reports content was scored
      by three judges (inter-rater reliability 85%). In the experimental group, 48 out
      of 485 (10%) sleep-onset reports were Tetris-related. They mostly consisted of
      images and sounds with very little emotional content. They exactly reproduced
      Tetris elements or mixed them with other mnemonic components. By contrast, in the
      first control group, only one report out of 107 was scored as Tetris-related
      (1%), and in the second control group only three reports out of 112 were scored
      as Tetris-related (3%; between-groups comparison; P = 0.006). Hypnagogic
      hallucinations were more consistently induced by experience than by anticipation
      (P = 0.039), and they were predominantly observed during the transition of
      wakefulness to sleep. The observed attributes of experience-related hypnagogic
      hallucinations are consistent with the particular organization of regional brain
      activity at sleep onset, characterized by high activity in sensory cortices and
      in the default-mode network.

PMID- 21848803
TI  - The prion protein binds thiamine.
AB  - Although highly conserved throughout evolution, the exact biological function of
      the prion protein is still unclear. In an effort to identify the potential
      biological functions of the prion protein we conducted a small-molecule screening
      assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was
      performed using a library of 149 water-soluble metabolites that are known to pass
      through the blood-brain barrier. Using a combination of 1D NMR, fluorescence
      quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a
      specific prion ligand with a binding constant of ~60 MUM. Subsequent studies
      showed that this interaction is evolutionarily conserved, with similar binding
      constants being seen for mouse, hamster and human prions. Various protein
      construct lengths, both with and without the unstructured N-terminal region in
      the presence and absence of copper, were examined. This indicates that the N
      terminus has no influence on the protein's ability to interact with thiamine. In
      addition to thiamine, the more biologically abundant forms of vitamin B1
      (thiamine monophosphate and thiamine diphosphate) were also found to bind the
      prion protein with similar affinity. Heteronuclear NMR experiments were used to
      determine thiamine's interaction site, which is located between helix 1 and the
      preceding loop. These data, in conjunction with computer-aided docking and
      molecular dynamics, were used to model the thiamine-binding pharmacophore and a
      comparison with other thiamine binding proteins was performed to reveal the
      common features of interaction.

PMID- 21848804
TI  - Induction of a stress response in Lactococcus lactis is associated with a
      resistance to ribosomally active antibiotics.
AB  - The acquisition of multidrug resistance in bacteria underlies the failure of
      antimicrobial therapy, and the emergence of pathogens that are resistant to
      almost the entire armoury of antibiotics. Among the proteins that can mediate or
      contribute to the drug-resistance profile in Gram-positive bacteria is a subset
      of ATP-binding cassette proteins that are comprised of a tandem-repeated
      nucleotide-binding domain. In this study, we expressed one of these NBD(2)
      proteins, LmrC, in an antibiotic-sensitive Gram-positive host strain (Lactococcus
      lactis) and demonstrated the acquisition of resistance to ribosomally active
      antibiotics. Mutation of key catalytic residues suggested that the resistance
      profile was the result of a cellular response, rather than being a function of
      the NBD(2) protein itself. This observation was confirmed by 2D SDS/PAGE, which
      demonstrated that the expression of the NBD(2) protein induced a stress response
      in L. lactis. A model combining this stress response induction and the
      acquisition of antibiotic resistance is proposed.

PMID- 21848805
TI  - Mass spectrometric characterization of proteins transferred from polyacrylamide
      gels to membrane filters.
AB  - In the 1990s, a technique was developed to transfer proteins from electrophoresis
      gels onto poly(vinylidene difluoride) (PVDF) membranes, digest the proteins on
      the membranes with proteases such as trypsin and analyze the resulting peptides
      on the membranes directly by mass spectrometry to identify the proteins. This
      technique, based on gel electrophoresis, is particularly useful for analyzing
      protein isoforms, splicing variants and post-translationally modified proteins.
      Previously, the low ionization efficiency of peptides immobilized on the
      membranes often rendered this technique useless. However, this technique has been
      improved by the use of PVDF membranes with a small pore size, which has enabled
      highly efficient and effective electroblotting and mass spectrometric analyses.
      Here, the advantage of this technique is discussed.

PMID- 21848806
TI  - Two contemporary cases of hepatitis associated with Teucrium chamaedrys L.
      decoction use: case reports and review of literature.
AB  - Teucrium chamaedrys L. is a herbaceous plant common in European woods that has
      been used for many purposes for centuries. Recently, T. chamaedrys L. has become
      popular as a slimming decoction without any scientific proof of efficacy
      notwithstanding its well-known hepatotoxicity. Hydroalcoholic extracts are
      currently used as flavourings in the preparation of wines, bitters and liqueurs.
      Teucrin A and teuchamaedryn A are the major toxic components of the diterpenoid
      fraction of T. chamaedrys L.

PMID- 21848807
TI  - Degradation of lignified secondary cell walls of lucerne (Medicago sativa L.) by
      rumen fungi growing in methanogenic co-culture.
AB  - AIMS: To compare the abilities of the monocentric rumen fungi Neocallimastix
      frontalis, Piromyces communis and Caecomyces communis, growing in coculture with
      Methanobrevibacter smithii, to colonize and degrade lignified secondary cell
      walls of lucerne (alfalfa) hay. METHODS AND RESULTS: The cell walls of xylem
      cylinders isolated from stems of lucerne contained mostly xylans, cellulose and
      lignin together with a small proportion of pectic polysaccharides. All of these
      major components were removed during incubation with the three fungi, and
      differing cell wall polysaccharides were degraded to different extents. The
      greatest dry weight loss was found with N. frontalis and least with C. communis,
      and scanning electron microscopy revealed that these extensively colonized
      different cell types. C. communis specifically colonized secondary xylem fibres
      and showed much less degradation than N. frontalis and P. communis. CONCLUSIONS:
      Neocallimastix frontalis and P. communis were efficient degraders of the cell
      walls of lucerne xylem cylinders. Degradation occurred of pectic polysaccharides,
      xylan and cellulose. Loss of lignin from the xylem cylinders probably resulted
      from the cleavage of xylan releasing xylan-lignin complexes. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Unlike rumen bacteria, the rumen fungi N. frontalis, P.
      communis and C. communis are able to degrade lignified secondary walls in lucerne
      stems. These fungi could improve forage utilization by ruminants and may have
      potential in the degradation of lignocellulosic biomass in the production of
      biofuels.

PMID- 21848808
TI  - Crk-associated substrate lymphocyte type regulates myeloid cell motility and
      suppresses the progression of leukemia induced by p210Bcr/Abl.
AB  - The p210Bcr/Abl and p190Bcr/Abl fusion oncoproteins are known to cause chronic
      myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Bcr/Abl
      phosphorylates several proteins that can lead to leukemogenesis. Crk-associated
      substrate lymphocyte type (Cas-L)/human enhancer of filamentation-1 (HEF1)/neural
      precursor cell expressed, developmentally down-regulated 9 (NEDD9) is an adapter
      protein at focal adhesions known to be associated with solid tumor metastasis.
      Crk-associated substrate lymphocyte type has also been reported to be tyrosine
      phosphorylated by p190Bcr/Abl. We demonstrated that Cas-L was expressed in murine
      granulocytes, as well as in lymphocytes, and that Cas-L-deficient (Cas-L(-/-) )
      granulocytes had increased migratory activity and decreased adhesiveness. To
      examine whether Cas-L was involved in leukemogenesis by p210Bcr/Abl, we generated
      Cas-L(-/-) p210Bcr/Abl transgenic mice. The mice displayed early development of
      myeloproliferative neoplasm seen in the chronic phase of CML, which resulted in
      the early death of the mice. Pathologically, increased infiltration of myeloid
      cells into several tissues was detected in the absence of Cas-L. In a
      hematopoietic reconstitution assay, Cas-L(-/-) p210Bcr/Abl transgenic cells
      showed a low population in the spleen, although only their myeloid cell
      population was normal. Thus, Cas-L seems to regulate the progression of CML in a
      negative way, presumably by attenuating extramedullary hyperplasia.

PMID- 21848809
TI  - Paternal deprivation affects the development of corticotrophin-releasing factor
      expressing neurones in prefrontal cortex, amygdala and hippocampus of the
      biparental Octodon degus.
AB  - Although the critical role of maternal care on the development of brain and
      behaviour of the offspring has been extensively studied, knowledge about the
      importance of paternal care is comparatively scarce. In biparental species,
      paternal care significantly contributes to a stimulating socio-emotional family
      environment, which most likely also includes protection from stressful events. In
      the biparental caviomorph rodent Octodon degus, we analysed the impact of
      paternal care on the development of neurones in prefrontal-limbic brain regions,
      which express corticotrophin-releasing factor (CRF). CRF is a polypeptidergic
      hormone that is expressed and released by a neuronal subpopulation in the brain,
      and which not only is essential for regulating stress and emotionality, but also
      is critically involved in cognitive functions. At weaning age [postnatal day
      (P)21], paternal deprivation resulted in an elevated density of CRF-containing
      neurones in the orbitofrontal cortex and in the basolateral amygdala of male
      degus, whereas a reduced density of CRF-expressing neurones was measured in the
      dentate gyrus and stratum pyramidale of the hippocampal CA1 region at this age.
      With the exception of the CA1 region, the deprivation-induced changes were no
      longer evident in adulthood (P90), which suggests a transient change that, in
      later life, might be normalised by other socio-emotional experience. The central
      amygdala, characterised by dense clusters of CRF-immunopositive neuropil, and the
      precentral medial, anterior cingulate, infralimbic and prelimbic cortices, were
      not affected by paternal deprivation. Taken together, this is the first evidence
      that paternal care interferes with the developmental expression pattern of CRF
      expressing interneurones in an age- and region-specific manner.

PMID- 21848811
TI  - Oxytocin suppresses basal glutamatergic transmission but facilitates activity
      dependent synaptic potentiation in the medial prefrontal cortex.
AB  - Both oxytocin and oxytocin receptors are implicated in neuropsychiatric
      disorders, particularly autism which involves a severe deficit in social
      cognition. Consistently, oxytocin enhances social cognition in humans and
      animals. The infralimbic medial prefrontal cortex (IL-mPFC) is believed to play
      an important role in the regulation of social cognition which might involve top
      down control of subcortical structures including the amygdala. However, little is
      known about whether and how oxytocin modulates synaptic function in the IL-mPFC.
      The effect of oxytocin on excitatory neurotransmission in the IL-mPFC was studied
      by examining both the evoked and spontaneous excitatory neurotransmission in the
      IL-mPFC layer V pyramidal neurons before and after perfusion with oxytocin. To
      investigate the effect of oxytocin on synaptic plasticity, low-frequency
      stimulation-induced long-lasting depression was studied in oxytocin-treated brain
      slices. Oxytocin produced a significant suppression of glutamatergic
      neurotransmission in the IL-mPFC layer V pyramidal neurons which was mediated by
      a reduction in glutamate release. Activation of the cannabinoid CB1 receptors was
      involved in this pre-synaptic effect. Treatment of brain slices with oxytocin for
      1 h converted long-lasting depression into long-lasting potentiation of
      glutamatergic neurotransmission. This oxytocin-mediated plasticity was NMDA
      receptor-dependent and was mediated by the synaptic insertion of calcium
      permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors.
      The aforementioned suppression of basal glutamatergic neurotransmission and
      facilitation of activity-dependent synaptic plasticity in the IL-mPFC might be
      critical for the effect of oxytocin on social cognition.

PMID- 21848810
TI  - N-terminal deletion does not affect alpha-synuclein membrane binding, self
      association and toxicity in human neuroblastoma cells, unlike yeast.
AB  - alpha-Synuclein causes Parkinson's disease if mutated or aberrantly produced in
      neurons. alpha-Synuclein-lipid interactions are important for the normal function
      of the protein, but can also contribute to pathogenesis. We previously reported
      that deletion of the first 10 N-terminal amino acids dramatically reduced lipid
      binding in vitro, as well as membrane binding and toxicity in yeast. Here we
      extend this study to human neuroblastoma SHSY-5Y cells, and find that in these
      cells the first 10 N-terminal residues do not affect alpha-synuclein membrane
      binding, self-association and cell viability, contrary to yeast. Differences in
      lipid composition, membrane fluidity and cytosolic factors between yeast and
      neuronal cells may account for the distinct binding behavior of the truncated
      variant in these two systems. Retinoic acid promotes differentiation and alpha
      synuclein oligomer formation in neuroblastoma cells, while addition of a
      proteasomal inhibitor induces neurite outgrowth and toxicity to certain wild-type
      and truncated alpha-synuclein clones. Yeast recapitulate several features of
      alpha-synuclein (patho)biology, but its simplicity sets limitations; verification
      of yeast results in more relevant model systems is, therefore, essential.

PMID- 21848812
TI  - Dermatologic manifestation of diabetes.
AB  - With the rising incidence of diabetes mellitus (DM) in the US, it is of paramount
      importance that practitioners understand the complications of DM and how best to
      manage them. Diabetes affects every organ system and the skin is no exception.
      There are numerous cutaneous manifestations of DM that have similar etiologies
      and result from the same pathologic mechanisms as the internal complications of
      this disease state. In addition, skin manifestations may precede the diagnosis of
      diabetes. The present article reviews both the common and less common cutaneous
      manifestations of DM, including presenting lesions, pathogenesis, and management.

PMID- 21848813
TI  - Antihyperglycemic activity of Ficus racemosa bark extract in type 2 diabetic
      individuals.

PMID- 21848814
TI  - The WxxxE effector EspT triggers expression of immune mediators in an Erk/JNK and
      NF-kappaB-dependent manner.
AB  - Enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and
      Citrobacter rodentium colonize their respective hosts while forming attaching and
      effacing lesions. Their infection strategy relies on translocation of a battery
      of type III secretion system effectors, including Map, EspM and EspT, which
      belong to the WxxxE/SopE family of guanine nucleotide exchange factors. Using the
      C. rodentium mouse model we found that EspT triggers expression of KC and
      TNFalpha in vivo. Indeed, a growing body of evidence suggests that, in addition
      to subversion of actin dynamics, the SopE and the WxxxE effectors activate
      signalling pathways involved in immune responses. In this study we found that
      EspT induces expression of the pro-inflammatory mediators cyclooxygenase-2 (COX
      2) an enzyme involved in production of prostaglandin E(2) (PGE2), interleukin
      (Il)-8 and Il-1beta in U937 human macrophages by activating the nuclear factor
      kappa-B (NF-kappaB), the extracellular signal-regulated kinases 1 and 2 (Erk1/2)
      and c-Jun N-terminal kinase (JNK) pathways. Since EspT modulates the activation
      of Cdc42 and Rac1, which mediates bacterial invasion into epithelial cells, we
      investigated the involvement of these Rho GTPases and bacterial invasion on pro
      inflammatory responses and found that (i) Rac1, but not Cdc42, is involved in
      EspT-induced Il-8 and Il-1beta secretion and (ii) cytochalasin D inhibits EspT
      induced EPEC invasion into U937 but not Il-8 or Il-1beta secretion. These results
      suggest that while EPEC translocates a number of effectors (i.e. NleC, NleD,
      NleE, NleH) that inhibit inflammation, a subset of strains, which encode EspT,
      employ an infection strategy that also involves upregulation of immune mediators.

PMID- 21848816
TI  - The endoscopic diagnosis of nonerosive reflux disease using flexible spectral
      imaging color enhancement image: a feasibility trial.
AB  - Nonerosive reflux disease (NERD) is classified into grade M (minimal change,
      endoscopically; erythema without sharp demarcation, whitish turbidity, and/or
      invisibility of vessels due to these findings) and grade N (normal) in the
      modified Los Angeles classification system in Japan. However, the classification
      of grades M and N NERD is not included in the original Los Angeles system because
      interobserver agreement for the conventional endoscopic diagnosis of grades M or
      N NERD is poor. Flexible spectral imaging color enhancement (FICE) is a virtual
      chromoendoscopy technique that enhances mucosal and vascular visibility. The aim
      of this study is to evaluate whether the endoscopic diagnosis of grades M or N
      NERD using FICE images is feasible. Between April 2006 and May 2008, 26 NERD
      patients and 31 controls were enrolled in the present study. First, an
      experienced endoscopist assessed the color pattern of minimal change in FICE
      images using conventional endoscopic images and FICE images side-by-side and
      comparing the proportion of minimal change between the two groups. Second, three
      blinded endoscopists assessed the presence or absence of minimal change in both
      groups using conventional endoscopic images and FICE images separately.
      Intraobserver variability was compared using McNemar's test, and interobserver
      agreement was described using the kappa value. Minimal changes, such as erythema
      and whitish turbidity, which were detected using conventional endoscopic images,
      showed up as navy blue and pink-white, respectively, in color using FICE images
      in the present FICE mode. The NERD group had a higher proportion of minimal
      change, compared with the control group (77% and 48%, respectively) (P= 0.033).
      In all three readers, the detection rates of minimal change using FICE images
      were greater than those using conventional endoscopic images (P= 0.025, <0.0001,
      and 0.034 for readers A, B, and C, respectively). The kappa values for all pairs
      of three readers using FICE images were between 0.683 and 0.812, while those
      using conventional endoscopic images were between 0.364 and 0.624. Thus, the
      endoscopic diagnosis of grades M or N NERD using FICE images is feasible and may
      improve interobserver agreement.

PMID- 21848815
TI  - The role of effectors of biotrophic and hemibiotrophic fungi in infection.
AB  - Biotrophic and hemibiotrophic fungi are successful groups of plant pathogens that
      require living plant tissue to survive and complete their life cycle. Members of
      these groups include the rust fungi and powdery mildews and species in the
      Ustilago, Cladosporium and Magnaporthe genera. Collectively, they represent some
      of the most destructive plant parasites, causing huge economic losses and
      threatening global food security. During plant infection, pathogens synthesize
      and secrete effector proteins, some of which are translocated into the plant
      cytosol where they can alter the host's response to the invading pathogen. In a
      successful infection, pathogen effectors facilitate suppression of the plant's
      immune system and orchestrate the reprogramming of the infected tissue so that it
      becomes a source of nutrients that are required by the pathogen to support its
      growth and development. This review summarizes our current understanding of the
      function of fungal effectors in infection.

PMID- 21848817
TI  - Dialogue at Davos for an aging world.

PMID- 21848818
TI  - Acute pancreatitis with normal lipase in an 80-year-old man.

PMID- 21848819
TI  - Abdominal wall hematomas associated with low-molecular-weight heparins: an
      important complication in older adults.

PMID- 21848821
TI  - Pretibial skin tears in older adults: a 2-year epidemiological study.

PMID- 21848820
TI  - A typical presentation with an atypical diagnosis.

PMID- 21848822
TI  - Celiac disease in older brazilians.

PMID- 21848824
TI  - Care-related goals of community-dwelling frail older adults.

PMID- 21848823
TI  - Perception of health students about older adults in Brazil.

PMID- 21848825
TI  - Patient and proxy rating agreements on activities of daily living and the
      instrumental activities of daily living of acutely hospitalized older adults.

PMID- 21848826
TI  - The vitamin "D-bate": what vascular risk in geriatric inpatients?

PMID- 21848828
TI  - Living with stairs: functioning in a large cohort of older Australian adults.

PMID- 21848827
TI  - Pulmonary features associated with being underweight in older men.

PMID- 21848829
TI  - Poor return of functional mobility after hip fracture in older patients-it's time
      to improve on hip fracture prevention.

PMID- 21848830
TI  - The 15-item geriatric depression scale as a predictor of mortality in older
      adults undergoing hemodialysis.

PMID- 21848831
TI  - Obstructive sleep apnea exacerbates endothelial dysfunction in people with
      metabolic syndrome.

PMID- 21848832
TI  - Relevant outcomes in intervention trials for sarcopenia.

PMID- 21848833
TI  - Language change with aging in Pelham Grenville Wodehouse and George Bernard Shaw.

PMID- 21848834
TI  - "Field medicine" for reconsidering "optimal aging".

PMID- 21848835
TI  - Geriatric medicine in the intensive care unit.

PMID- 21848837
TI  - Does ketamine improve postoperative analgesia? More questions than answers.

PMID- 21848838
TI  - Chronic pain, medical students, and primary care commentary on "What can we learn
      from first-year medical students' perception of pain in the primary care
      setting".

PMID- 21848839
TI  - Learning from our learners: implications for pain management education in medical
      schools.

PMID- 21848840
TI  - Re: Comparison of the effectiveness of lumbar transforaminal epidural injection
      with the particulate and nonparticulate corticosteroids in lumbar radiating pain.

PMID- 21848843
TI  - Extensive clonal spread and extreme longevity in saw palmetto, a foundation
      clonal plant.
AB  - The lack of effective tools has hampered out ability to assess the size, growth
      and ages of clonal plants. With Serenoa repens (saw palmetto) as a model, we
      introduce a novel analytical framework that integrates DNA fingerprinting and
      mathematical modelling to simulate growth and estimate ages of clonal plants. We
      also demonstrate the application of such life-history information of clonal
      plants to provide insight into management plans. Serenoa is an ecologically
      important foundation species in many Southeastern United States ecosystems; yet,
      many land managers consider Serenoa a troublesome invasive plant. Accordingly,
      management plans have been developed to reduce or eliminate Serenoa with little
      understanding of its life history. Using Amplified Fragment Length Polymorphisms,
      we genotyped 263 Serenoa and 134 Sabal etonia (a sympatric non-clonal palmetto)
      samples collected from a 20 * 20 m study plot in Florida scrub. Sabal samples
      were used to assign small field-unidentifiable palmettos to Serenoa or Sabal and
      also as a negative control for clone detection. We then mathematically modelled
      clonal networks to estimate genet ages. Our results suggest that Serenoa
      predominantly propagate via vegetative sprouts and 10,000-year-old genets may be
      common, while showing no evidence of clone formation by Sabal. The results of
      this and our previous studies suggest that: (i) Serenoa has been part of scrub
      associations for thousands of years, (ii) Serenoa invasion are unlikely and (ii)
      once Serenoa is eliminated from local communities, its restoration will be
      difficult. Reevaluation of the current management tools and plans is an urgent
      task.

PMID- 21848844
TI  - Effect of several supplemental Chinese herbs additives on rumen fermentation,
      antioxidant function and nutrient digestibility in sheep.
AB  - Two experiments were carried out in this study. Experiment 1 was conducted to
      examine the effects of several supplemental Chinese herbs on antioxidant function
      and slaughtered body weight in sheep. Results indicated that Fructus Ligustri
      Lucidi supplementation improved the blood antioxidant function [higher
      concentration of glutathione reductase (GR), superoxide dismutase and lower
      concentration of malondialdehyde] and slaughtered body weight in sheep (p <
      0.05). Experiment 2 was conducted to investigate the effect of Fructus Ligustri
      Lucidi extract (FLLE) on rumen fermentation and nutrient digestibility in sheep.
      Four levels of FLLE treatments, i.e. 0, 100, 300 and 500 mg/kg dry matter (DM),
      were used in this part. Addition of FLLE at 300 or 500 mg/kg DM increased total
      volatile fatty acid (VFA) concentration and propionate proportion, decreased
      ammonia-N concentration in the ruminal fluid, reduced blood urea nitrogen
      concentration at 2, 4, 6 and 8 h after morning feeding (p < 0.05). Addition of
      FLLE at all dosages had no effect on ruminal pH value and acetate concentration
      at all sampling time points in sheep (p > 0.05). Dynamic degradation coefficient
      c of maize DM was significantly increased by supplementing FLLE at 300 or 500
      mg/kg DM (p < 0.05). Fructus Ligustri Lucidi extract addition had no effect on
      degradation coefficients a, b, c of DM and nitrogen of soybean meal; a, b of
      maize DM; a, b, c of maize nitrogen; and a, b, c of neutral detergent fibre (NDF)
      and acid detergent fibre (ADF) of Chinese wildrye (p > 0.05). Addition of FLLE at
      300 or 500 mg/kg DM increased DM and organic matter digestibility of diet (p <
      0.05). Fructus Ligustri Lucidi extract addition had no effect on digestibility of
      diet's NDF, ADF and crude protein (p > 0.05). From the aforementioned results, it
      is indicated that FLLE improved antioxidant status and slaughtered body weight.
      Fructus Ligustri Lucidi extract addition has capability to modulate rumen
      fermentation, increase the maize degradation rate, total volatile fatty acid
      concentration and propionate proportion in sheep.

PMID- 21848845
TI  - A de novo synthesis citrate transporter, Vigna umbellata multidrug and toxic
      compound extrusion, implicates in Al-activated citrate efflux in rice bean (Vigna
      umbellata) root apex.
AB  - Al-activated organic acid anion efflux from roots is an important Al resistance
      mechanism in plants. We have conducted homologous cloning and isolated Vigna
      umbellata multidrug and toxic compound extrusion (VuMATE), a gene encoding a de
      novo citrate transporter from rice bean. Al treatment up-regulated VuMATE
      expression in the root apex, but neither in the mature root region nor in the
      leaf. The degree of up-regulation of VuMATE was both partially Al concentration
      and time dependent, consistent with the delay in the onset of the Al-induced
      citrate efflux in rice bean roots. While La(3+)  moderately induced VuMATE
      expression, Cd(2+)  and Cu(2+)  did not induce the expression.
      Electrophysiological analysis of Xenopus oocytes expressing VuMATE indicated this
      transporter can mediate significant anion efflux across the plasma membrane.
      [(14) C]citrate efflux experiments in oocytes demonstrated that VuMATE is a H(+) 
      dependent citrate transporter. In addition, expression of VuMATE in transgenic
      tomato resulted in increased Al resistance, which correlated with an enhanced
      citrate efflux. Taken together, these findings suggest that VuMATE is a
      functional homolog of the known citrate transporters in sorghum, barley, maize
      and Arabidopsis. The similarities and differences of all the known citrate
      transporters associated with Al stress in the MATE family are also discussed.

PMID- 21848846
TI  - The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes.
AB  - The formation of the glial scar following a spinal cord injury presents a
      significant barrier to the regenerative process. It is primarily composed of
      chondroitin sulfate proteoglycans (CSPGs) that can inhibit axonal sprouting and
      regeneration. Although the inhibitory effects on neurons are well documented,
      little is known about their effects on oligodendrocyte progenitor cells (OPCs).
      In this study, we examined the effects of CSPGs on OPC process outgrowth and
      differentiation in vitro. The results show that specific CSPGs, in particularly
      those highly up-regulated following spinal cord injury, inhibit OPC process
      outgrowth and differentiation, and that treatment with chondroitinase ABC can
      completely reverse this inhibition. Additionally, treatment with the Rho kinase
      inhibitor Y-27632 also reverses the observed inhibition, implicating the
      activation of Rho kinase in the CSPG inhibition of OPC growth. Taken together,
      these findings demonstrate that the CSPGs found within the glial scar are not
      only inhibitory to neurons, but also to OPCs. Moreover, this study shows that
      chondroitinase ABC treatment, having shown promise in promoting axonal
      regeneration, may also enhance remyelination.

PMID- 21848847
TI  - Exploring the pattern of blood donor beliefs in first-time, novice, and
      experienced donors: differentiating reluctant altruism, pure altruism, impure
      altruism, and warm glow.
AB  - BACKGROUND: Using constructs from the Theory of Planned Behavior and theories of
      altruism, this article explores how multiple motivations and beliefs for blood
      donation are clustered and change across the donor career. In so doing important
      distinctions, for blood donation, between impure altruism, pure altruism, and
      warm glow are explored. STUDY DESIGN AND METHODS: Measures of intentions,
      cognitive and affective attitudes, role merger, pure altruism, trust, self
      efficacy, subjective and moral norms, and habit formation were assessed in a
      sample of 12,580 whole blood donors. Analyses showed that a distinction between
      first-time, novice (one to four donations), and experienced donors (five or more
      donations) is justified. Principal components analysis and confirmatory factor
      analytic Multiple-Indicator Multiple-Causal models were used to compare models
      across these groups. RESULTS: A cognition-behavior (CB) factor, including
      intentions, was common to all groups. First-time and novice donors were marked by
      a newly identified motivational factor: "reluctant altruism" (i.e., the
      motivation to donate because of a lack of trust in others). First-time donors
      exhibited an impure altruism factor whereas for experienced donors warm glow and
      pure altruism factors were observed. For first-time donors impure altruism and
      reluctant altruism were both associated with the CB factor in females and impure
      altruism only in males. For both sexes reluctant altruism was associated of the
      CB factor in novice donors and warm glow and pure altruism for experienced
      donors. CONCLUSIONS: New avenues for intervention are suggested by the emergence
      of reluctant altruism for novice donors and warm glow for experienced donors. The
      importance of distinguishing aspects of altruism is highlighted.

PMID- 21848848
TI  - Impact of different inclusion levels of oil palm (Elaeis guineensis Jacq.) fronds
      on fatty acid profiles of goat muscles.
AB  - The effects of different inclusion levels of oil palm fronds (OPF) on the fatty
      acid profile of the longissimus dorsi (LD), biceps femoris (BF) and infraspinatus
      (IS) muscle of goats fed for 100 days are described. Twenty-four individually
      housed Kacang crossbred male goats (averaged 21.7 +/- 0.97 kg BW) were allocated
      to three groups receiving either a 100% concentrate control diet (CON), diet with
      25% inclusion level of OPF (HAF) or a diet with 50% inclusion of OPF. The diets
      were adjusted to be isocaloric and isonitrogenous and fed at 3.0% of BW daily.
      Samples of LD, BF and IS muscles were taken at slaughter for the determination of
      fatty acid profiles. The total saturated fatty acids (SFA) in the LD and BF
      muscles of the OPF group were significantly (p < 0.05) lower than the CON group.
      For all muscles, C18:3n-3 and total n-3 polyunsaturated fatty acid (PUFA) were
      significantly higher (p < 0.05) in the OPF group than the CON group with minimal
      impact on the C18:2n-6 and total n-6PUFA. Consequently, the n-6:n-3 ratio
      significantly (p < 0.05) decreased in the OPF group compared to the CON group.
      The LD muscle had a significantly higher conjugated linoleic acid 18:2 c19t11
      compared to other muscles. There were no interactions between muscle x diet
      except for total SFA. It is concluded that OPF at 25-50% inclusion levels may
      decrease the SFA and increase the n-3PUFA content in chevon, with no apparent
      adverse effects on the growth performance of the animals, can be used as a feed
      ingredient to support goat farming in countries that lack grazing pasture.

PMID- 21848849
TI  - Effects of alpha-lipoic acid supplementation on antioxidative ability and
      performance of sows and nursing piglets.
AB  - The current study was carried out to determine the effects of alpha-lipoic acid
      (LA) supplementation during late-gestation and lactation on antioxidative ability
      and performance of sows and their nursing piglets. A total of 160 multiparous
      sows were randomly allocated to four treatments with 40 replicates per treatment
      according to parity number and backfat (BF) thickness. Sows were fed 1 of 4 diets
      from day 85 of gestation to day 21 of lactation. Diets were control without LA;
      400 ppm LA supplementation; 600 ppm LA supplementation; and 800 ppm LA
      supplementation. BF thickness of sows was determined on day 85 and 110 of
      gestation and days 1 and 21 of lactation. Piglet bodyweight was measured at
      birth, days 7, 14 and 21. Blood samples were obtained from the sows, and average
      daily feed intake (ADFI) of the sows during lactation was recorded. There were no
      differences in BF thickness or ADFI among treatment groups. Dietary LA
      supplementation resulted in a decrease in blood urea nitrogen (p < 0.01)
      concentration at days 110 of gestation. Dietary 800 ppm LA increased serum
      glutathione peroxidase (GSH-Px) activity (p < 0.05) and reduced maleic dialdehyde
      levels (p < 0.01) of sows compared with the control diet at days 21 of lactation.
      Alpha-lipoic acid supplementation increased the birthweight and weaning weight of
      piglets (p < 0.01) compared with the control group. Weight gains of piglets from
      sows fed the 800 ppm LA diets were greater (p < 0.01) between days 7 and 14
      compared with piglets from control sows. Weight gains of piglets from sows fed
      the LA-supplemented diets were greater between days 14 and 21 (p < 0.05) and
      between days 1 and 21 (p < 0.01) compared with piglets from control-fed sows. In
      conclusion, the results indicate that antioxidant LA was effective in enhancing
      antioxidant enzymes activity and improving the performance of sows and their
      nursing piglets.

PMID- 21848850
TI  - Comparative studies on temperature threshold for heat shock protein 70 induction
      in young and adult Murrah buffaloes.
AB  - To know the temperature threshold for heat shock protein 70 (HSP70) induction in
      lymphocytes and to assess physiological changes, if any, in relation to HSP70
      induction in young and adult Murrah buffaloes, this study was divided into two
      parts: I. In vivo study: where assay of HSP70 was performed in blood samples
      collected from acutely exposed young and adult Murrah buffaloes (n = 6) inside a
      climatic chamber at 40, 42 and 45  degrees C for 4 h and thermoneutral
      temperature (22  degrees C). Physiological parameters viz., rectal temperature,
      respiratory rate, pulse rate and skin temperature of different body parts were
      monitored to assess magnitude of stress in the animals owing to thermal exposure
      II. For in vitro study, equal numbers of lymphocyte cells were separated from
      blood collected from young and adult buffaloes and were subjected to four
      temperature treatments (38, 40, 42 and 45  degrees C) for 4 h. A significant
      increase (p < 0.05) in all the physiological parameters in both young and adult
      buffaloes was observed after exposure to 40, 42 and 45  degrees C for 4 h as
      compared to 38  degrees C. The average plasma HSP70 concentrations (ng/ml) were
      significantly higher (p < 0.05) at 40, 42 and 45  degrees C as compared to 38 
      degrees C in both young and adult and were higher in young than adult buffaloes
      at 38 and 45  degrees C. Heat shock protein 70 level in lymphocyte lysate showed
      highest concentration after 3-h exposure to all temperatures (40, 42 and 45 
      degrees C) in both young and adult buffaloes. The intensity of changes of all
      physiological parameters was more in young animals than in the adults indicating
      the greater susceptibility of younger animals to heat stress and was found to be
      changed at around 40  degrees C when animals were exposed to different
      temperatures, indicating the possibility that HSP70 production may be initiated
      at this temperature which is 2 or 3  degrees C higher than core body temperature.

PMID- 21848851
TI  - From personal challenge to technical fix: the risks of depersonalised care.
AB  - Our research focuses on the complexity of needs associated with distress in
      people with advanced cancer. We have recently completed a large longitudinal
      survey exploring the interplay between a number of components of distress,
      including depression, demoralisation, debility and spirituality, amongst a cohort
      of people living with terminal cancer. Participants were recruited from 25
      hospices across the Northwest of England between 2007-2009. A purposive subsample
      of 27 people was invited to take part in a qualitative interview to explore in
      greater depth their personal experiences of living with illness and related
      distress. Holistic-content analysis revealed two emerging themes: 'personal or
      personalised care' and 'expectations of truth and certainty'. We discuss these
      themes in the light of Illich's critique of health care as a 'technical response
      to a personal challenge'. We highlight the need for further work to explore the
      impact of organisation of care on personalised need and suggest looking to the
      chronic illness self-management literature for help in developing future
      palliative care approaches.

PMID- 21848852
TI  - Can post-acute care programmes for older people reduce overall costs in the
      health system? A case study using the Australian Transition Care Programme.
AB  - There is an increasing demand for acute care services due in part to rising
      proportions of older people and increasing rates of chronic diseases. To reduce
      pressure and costs in the hospital system, community-based post-acute care
      discharge services for older people have evolved as one method of reducing length
      of stay in hospital and preventing readmissions. However, it is unclear whether
      they reduce overall episode cost or expenditure in the health system at a more
      general level. In this paper, we review the current evidence on the likely costs
      and benefits of these services and consider whether they are potentially cost
      effective from a health services perspective, using the Australian Transition
      Care Programme as a case study. Evaluations of community-based post-acute
      services have demonstrated that they reduce length of stay, prevent some re
      hospitalisations and defer nursing home placement. There is also evidence that
      they convey some additional health benefits to older people. An economic model
      was developed to identify the maximum potential benefits and the likely cost
      savings from reduced use of health services from earlier discharge from hospital,
      accelerated recovery, reduced likelihood of readmission to hospital and delayed
      entry into permanent institutional care for participants of the Transition Care
      Programme. Assuming the best case scenario, the Transition Care Programme is
      still unlikely to be cost saving to a healthcare system. Hence for this service
      to be justified, additional health benefits such as quality of life improvements
      need to be taken into account. If it can be demonstrated that this service also
      conveys additional quality of life improvements, community-based programmes such
      as Transition Care could be considered to be cost-effective when compared with
      other healthcare programmes.

PMID- 21848853
TI  - The perceptions of and disincentives for receiving influenza A (H1N1) vaccines
      among chronic renal disease patients in Hong Kong.
AB  - This article aims to demonstrate the perceptions of patients with chronic renal
      disease in Hong Kong towards the new vaccine for influenza A (H1N1), as well as
      the main disincentives. Little is known about the views of chronically ill
      patients on the H1N1 vaccine and even less about the underlying factors that
      motivate its low acceptance by this group. To explore these issues, this study
      adopted a qualitative approach by conducting in-depth, semi-structured interviews
      with 40 chronic renal disease patients in Hong Kong from December 2009 to March
      2010. The participants were selected by purposive sampling from a patient with
      renal disease self-help alliance, which has over 4000 members with chronic renal
      diseases coming from nine public hospitals. Data were analysed using thematic
      content analysis. Although vaccination was portrayed as one of the most effective
      methods to prevent influenza A (H1N1), chronically ill participants in this study
      showed reluctance towards it. Six disincentives for them to receive H1N1 vaccines
      were identified: perceptions of H1N1 vaccine as unsafe, cultural perception of
      vaccines as harmful, the belief that seasonal influenza vaccines provided
      immunity against influenza A (H1N1), inaccessibility for receiving the H1N1
      vaccine, worries in contracting infectious diseases from vaccination locations
      and the financial cost. As chronically ill patients are one of the high-risk
      groups who can suffer from severe complications from influenza, understanding the
      underlying social, cultural and perceptual factors that prevent their
      immunisation is crucial to the design of a public health policy responsive to
      their needs.

PMID- 21848854
TI  - Preterm infants' early developmental status is associated with later
      developmental outcome.
AB  - AIM: To assess the development of preterm infants from 40 weeks gestational age
      to 18 months corrected age to identify early predictors of later development.
      METHODS: Fifty-one infants were involved. Infant development was assessed at 40
      and 44 weeks gestational age with the Brazelton neonatal behavioral assessment
      scale and a self-regulation scale and at 3, 6, 10, 18 months corrected age with
      the Bayley Scales of Infant Development. The quality of general movements was
      assessed at 1 and 3 months corrected age and maternal attachment style at
      infant's age of 6 months corrected age with the Relation Scale Questionnaire.
      RESULTS: At term age and 1-month corrected age, preterm infants were less mature
      and had lower levels of self-regulation than full-term infants. At 3 months
      corrected age, a higher proportion of preterm infants (43%) had mildly abnormal
      motor quality compared to the general population (25%). At all follow-ups,
      preterm infants had delayed mental, motor and behavioural development, which was
      associated with the level of self-regulation, motor quality and maternal
      attachment style. Maternal education level was the most predominant background
      factor related to infant development. CONCLUSION: Preterm infants show early-in
      life deviations in self-regulation, motor quality and development. These
      deviations are risk factors for later optimal functioning.

PMID- 21848855
TI  - Crohn's disease patients with chronic intestinal failure receiving long-term
      parenteral nutrition: a cross-national adult study.
AB  - BACKGROUND: Chronic intestinal failure (CIF) is a very rare Crohn's disease (CD)
      complication. AIM:   To determine incidence of CIF treated with home parenteral
      nutrition (HPN) in adult CD patients and to isolate factors associated with
      severe CIF. METHODS: This retrospective multicentre study included 38 patients
      with CD-related CIF treated with HPN for at least 12 months in French HPN
      centres. Severe CIF was defined by a length of remnant small bowel of less than
      100 cm or CIF occurrence within the 15 years following CD diagnosis. RESULTS:
      Median delay between CD diagnosis and CIF was 15 years. CIF incidence did not
      decrease over time (1.4/year before 1995 vs. 2.2/year after). Median number of
      small bowel resections per patient was three (range 1-8). Median small bowel
      resection, remnant and initial lengths were 160, 80 and 260 cm, respectively.
      Twenty-four per cent of patients developed stenosis within 1 year after CD
      diagnosis and 76% developed perforative complications within 2 years. In
      multivariate analysis, severe CIF, defined as CIF onset <15 years after CD
      diagnosis, was associated with a more recent CD diagnosis (odds ratio, 0.785; 95%
      confidence interval, 0.623-0.989). CIF occurred despite frequent use of
      immunosuppressants. Course of CD remained severe during HPN: immunosuppressants
      prescription occurred in 11 patients, surgery in six. Six patients died from CD
      (n = 2), HPN complications (n = 2) or other causes (n = 2). CONCLUSIONS: Chronic
      intestinal failure requiring HPN is rare during CD. Incidence remained stable
      over time. Surgical procedures play a minor role in the occurrence of severe
      chronic intestinal failure compared to CD severity.

PMID- 21848856
TI  - Faecal chitinase 3-like-1: a novel biomarker of disease activity in paediatric
      inflammatory bowel disease.
AB  - BACKGROUND: Chitinase 3-like-1 (CHI3L1) is up-regulated in the inflamed mucosa of
      inflammatory bowel disease (IBD). AIM: To evaluate the usefulness of a faecal
      CHI3L1 assay, as a reliable marker for predicting the severity of paediatric IBD.
      METHODS: Faecal samples were obtained from ulcerative colitis (UC, n = 94),
      Crohn's disease (CD, n = 87), and healthy individuals (n = 56). The faecal CHI3L1
      and calprotectin levels were determined by ELISA. For endoscopic evaluation, the
      sum of the Matts' score for UC and the simple endoscopic score for CD (SES-CD)
      were used. Ileal lesions were evaluated by ultrasonography. RESULTS: Faecal
      CHI3L1 levels were significantly elevated in active UC (median 366.6 ng/g, n =
      44) and active CD (median 632.7 ng/g, n = 48) patients, as compared with healthy
      individuals (median 2.2 ng/g, n = 56). In UC patients, the faecal CHI3L1 levels
      were positively correlated with the sum of the Matts' score (r = 0.73, P < 0.01,
      n = 42). In CD patients, there was a significant correlation between faecal
      CHI3L1 levels and endoscopic activity as determined by the SES-CD scoring system
      (r = 0.61, P < 0.01, n = 25). The faecal CHI3L1 levels of patients with wall
      thickening of their small intestine were significantly higher than those of
      healthy controls or patients without wall thickening. The cutoff value of 13.7
      ng/g for fecal CHI3L1(the 95th percentile of the control value) predicted active
      lesions in IBD patients with a sensitivity of 84.7% and a specificity of 88.9%.
      CONCLUSION: Faecal CHI3L1 assays may be useful for predicting the severity and
      activity of mucosal inflammation in IBD.

PMID- 21848857
TI  - Early symptomatic response and mucosal healing with mesalazine rectal suspension
      therapy in active distal ulcerative colitis--additional results from two
      controlled studies.
AB  - BACKGROUND: Rapid resolution of symptoms and endoscopic inflammation in
      ulcerative colitis (UC) represent important treatment goals. AIMS: To establish
      times to bleeding cessation and endoscopic healing for topical and oral
      mesalazine in active distal UC, a post hoc analysis of two published studies was
      performed. METHODS: Study I (Sutherland 1987) compared mesalazine rectal
      suspension to placebo, while Study II (Safdi 1997) compared topical suspensions,
      either alone or in combination with oral mesalazine, and oral alone. Cessation of
      rectal bleeding (RB) was defined as absence of bleeding on four consecutive days.
      Endoscopic remission was defined as DAI mucosal healing (MH) subscore=0 and
      clinical remission as MH subscore =0-1 and >= 1-point improvement, plus RB
      subscore = 0. RESULTS: Study I: By Day 2, 31.4% of subjects using topical
      monotherapy reported no RB vs. 5.5% in the placebo arm (P<0.0006); median time to
      RB cessation was 8 days. Significantly higher rates of endoscopic (25.0% vs.
      7.8%, P<0.005) and clinical remission (48.6% vs. 9.6%, P<0.0001) were observed at
      Week 3. Study II: A significantly higher proportion of subjects achieved RB
      cessation with combination therapy vs. oral therapy, commencing by Day 8. By Week
      3, a significantly higher proportion of subjects using combination therapy
      achieved clinical remission compared to oral therapy alone (57.9% vs. 18.2%,
      P<0.05). CONCLUSIONS: Topical mesalazine suspension, either alone or in
      combination with oral mesalazine, led to earlier rectal bleeding cessation and
      mucosal healing. These data support use of topical therapy for more rapid
      treatment benefit in active distal ulcerative colitis.

PMID- 21848858
TI  - Education and support needs of the older adult with congenital heart disease.
AB  - AIM:   This article is a report of a study exploring health-related quality of
      life in adults with congenital heart disease and the extent to which it is
      associated with patients' illness beliefs and emotional health. BACKGROUND:   A
      reduction in mortality in patients with congenital heart disease has led to an
      increasingly older population that faces new challenges. Studies in a younger
      adult population have reported inconsistent findings regarding health-related
      quality of life. Factors such as, the complexity of the congenital heart defect,
      have not been found to be associated with quality of life. The association
      between illness beliefs and health-related quality of life has not previously
      been reported. METHOD:   A cross-sectional questionnaire study of adults with
      congenital heart disease attending an outpatient clinic in a specialist centre in
      the United Kingdom between October 2007 and May 2008. RESULTS:   The mean age of
      the study population was 37.2 years. Participants reported poorer physical
      functioning, role functioning and general health than a general population. High
      levels of anxiety were reported in 38% and high levels of depression in 17%. In
      multivariate analysis, higher levels of anxiety and depression were associated
      with poorer mental functioning and higher levels of depression with poorer
      physical quality of life. CONCLUSION:   We have reported that high levels of
      anxiety and depression in an older population of patients with congenital heart
      disease are associated with poorer quality of life. This highlights the need to
      routinely assess anxiety and depression in this patient group and to provide
      psychological support appropriately.

PMID- 21848859
TI  - Three-dimensional xylem networks and phyllode properties of co-occurring Acacia.
AB  - Reduced leaf size is often correlated to increased aridity, where smaller leaves
      demand less water via xylem conduits. However, it is unknown if differences in
      three-dimensional (3D) xylem connectivity reflect leaf-level adaptations. We used
      X-ray microtomography (micro-CT) to quantify 3D xylem connectivity in ~5 mm
      diameter branch sections of co-occurring semi-arid Acacia species of varied
      phyllode size. We compared 3D connectivity to minimum branch water potential and
      two-dimensional (2D) vessel attributes derived from sections produced by micro
      CT. 2D attributes included vessel area, density, vessel size to number ratio (S)
      and vessel lumen fraction (F). Trees with terete phyllodes had less negative
      water potentials than broad phyllode variants. 3D xylem connectivity was
      conserved across all trees regardless of phyllode type or minimum water
      potential. We also found that xylem connectivity was sensitive to vessel lumen
      fraction (F) and not the size to number ratio (S) even though F was consistent
      among species and phyllode variants. Our results demonstrate that differences in
      phyllode anatomy, and not xylem connectivity, likely explain diversity of drought
      tolerance among closely related Acacia species. Further analysis using our
      approach across a broader range of species will improve understanding of
      adaptations in the xylem networks of arid zone species.

PMID- 21848860
TI  - Novel temporal, fine-scale and growth variation phenotypes in roots of adult
      stage maize (Zea mays L.) in response to low nitrogen stress.
AB  - There is interest in discovering root traits associated with acclimation to
      nutrient stress. Large root systems, such as in adult maize, have proven
      difficult to be phenotyped comprehensively and over time, causing target traits
      to be missed. These challenges were overcome here using aeroponics, a system
      where roots grow in the air misted with a nutrient solution. Applying an
      agriculturally relevant degree of low nitrogen (LN) stress, 30-day-old plants
      responded by increasing lengths of individual crown roots (CRs) by 63%,
      compensated by a 40% decline in CR number. LN increased the CR elongation rate
      rather than lengthening the duration of CR growth. Only younger CR were
      significantly responsive to LN stress, a novel finding. LN shifted the root
      system architectural balance, increasing the lateral root (LR)-to-CR ratio,
      adding ~70 m to LR length. LN caused a dramatic increase in second-order LR
      density, not previously reported in adult maize. Despite the near-uniform
      aeroponics environment, LN induced increased variation in the relative lengths of
      opposing LR pairs. Large-scale analysis of root hairs (RHs) showed that LN
      decreased RH length and density. Time-course experiments suggested the RH
      responses may be indirect consequences of decreased biomass/demand under LN.
      These results identify novel root traits for genetic dissection.

PMID- 21848861
TI  - Experimental research with synthetic copolymer-coated cardiopulmonary bypass
      circuits: inflammatory and thrombogenicity analysis.
AB  - This study aimed to assess complement system activation and index of
      thrombogenicity and platelet aggregation between synthetic copolymer-coated
      cardiopulmonary bypass (CPB) circuit and conventional CPB circuit. Twenty-six
      pigs were equally divided into two groups--the conventional group and the coated
      group. They were placed on CPB for 90 min, and blood samples were collected at
      three different time points (T0, right before CPB establishment; T1, 45 min after
      starting CPB; and T2, 90 min after starting CPB) to measure total count of
      inflammatory cells (leukocytes, neutrophils, lymphocytes, and platelets) and
      serum levels of fraction C3 of complement system. Upon completion of the 90-min
      CPB, fragments of different compartments of the CPB circuit were taken for
      assessing index of thrombogenicity and platelet aggregation. There were no
      differences between both groups regarding total count of leukocytes, neutrophils,
      and lymphocytes; however, there was a lower count of platelets at T2 in the
      coated group (P = 0.020). The serum level of fraction C3 was lower in the coated
      group at T1 (P = 0.020) and T2 (P = 0.017). Higher index of thrombogenicity and
      platelet aggregation were detected in the conventional group (77% of the animals
      within the conventional group) than in the coated group (46% of the animals
      within the coated group). In conclusion, in heart surgery requiring CPB, the use
      of synthetic copolymer-coated CPB circuit may be useful to reduce complement
      system activation, as well as attenuating index of thrombogenicity and platelet
      aggregation.

PMID- 21848862
TI  - Down-regulation of SymRK correlates with a deficiency in vascular bundle
      development in Phaseolus vulgaris nodules.
AB  - The symbiotic interaction of legumes and rhizobia results in the formation of
      nitrogen-fixing nodules. Nodulation depends on the finely coordinated expression
      of a battery of genes involved in the infection and the organogenesis processes.
      After Nod factor perception, symbiosis receptor kinase (SymRK) receptor triggers
      a signal transduction cascade essential for nodulation leading to cortical cell
      divisions, infection thread (IT) formation and final release of rhizobia to the
      intracellular space, forming the symbiosome. Herein, the participation of SymRK
      receptor during the nodule organogenesis in Phaseolus vulgaris is addressed. Our
      findings indicate that besides its expression in the nodule epidermis, in IT, and
      in uninfected cells of the infection zone, PvSymRK immunolocalizes in the root
      and nodule vascular system. On the other hand, knockdown expression of PvSymRK
      led to the formation of scarce and defective nodules, which presented alterations
      in both IT/symbiosome formation and vascular system.

PMID- 21848863
TI  - Thrombosis of tunneled-cuffed hemodialysis catheters: treatment with high-dose
      urokinase lock therapy.
AB  - Thrombosis-related malfunction of tunneled-cuffed central venous catheters (TCC)
      for hemodialysis (HD) currently leads to a high rate of untimely catheter
      removal. Urokinase (UK) therapy is used for TCC thrombosis/malfunction, but no
      consensus exists on the adequate dose to obtain thrombolysis. We selected 72 HD
      patients with TCC and a mean age and HD vintage of 74 years (range 65-87) and 36
      months (range 12-61), respectively. All patients received warfarin therapy with a
      target international normalized ratio (INR) of 1.8-2.5. Coagulative assessment of
      the patients was obtained by checking the INR, activated partial thromboplastin
      time, fibrinogen, hemoglobin, and platelets. Sixty-five thrombotic events were
      recorded during a 3-year follow-up (median 0.3 events/patient/year). The patients
      selected were randomized into two groups according to a different thrombolytic
      therapy. Group A comprised 29 thrombotic events in 32 patients who received UK
      25,000 IU in both arterial and venous lines of the TCC for each event. UK
      restored an adequate blood flow rate (BFR) for HD (>= 250 mL/min) in 4/29 events
      (13.7%), whereas addition of 50,000 IU to both arterial and venous lines was
      required in 25/29 events (86.3%). For the same 25 events in the second HD
      session, a further 75,000 IU of UK was needed for each TCC lumen. Group B
      comprised 36 thrombotic events in 40 patients who received 100 000 IU of UK in
      the arterial and venous lumen of the TCC for each event. An adequate BFR was
      recovered in all events. In 12/36 events (33.3%), 100,000 IU UK for both lumens
      were needed in the second HD. In conclusion, group B patients obtained (i) a
      significantly better TCC patency than group A patients; (ii) a low UK
      administration in the following HD sessions; and (iii) no bleeding complications.

PMID- 21848864
TI  - Infection dynamics of endemic malaria in a wild bird population: parasite species
      dependent drivers of spatial and temporal variation in transmission rates.
AB  - 1. Investigating the ecological context in which host-parasite interactions occur
      and the roles of biotic and abiotic factors in forcing infection dynamics is
      essential to understanding disease transmission, spread and maintenance. 2.
      Despite their prominence as model host-pathogen systems, the relative influence
      of environmental heterogeneity and host characteristics in influencing the
      infection dynamics of avian blood parasites has rarely been assessed in the wild,
      particularly at a within-population scale. 3. We used a novel multievent
      modelling framework (an extension of multistate mark-recapture modelling) that
      allows for uncertainty in disease state, to estimate transmission parameters and
      assess variation in the infection dynamics of avian malaria in a large,
      longitudinally sampled data set of breeding blue tits infected with two divergent
      species of Plasmodium parasites. 4. We found striking temporal and spatial
      heterogeneity in the disease incidence rate and the likelihood of recovery within
      this single population and demonstrate marked differences in the relative
      influence of environmental and host factors in forcing the infection dynamics of
      the two Plasmodium species. 5. Proximity to a permanent water source greatly
      influenced the transmission rates of P. circumflexum, but not of P. relictum,
      suggesting that these parasites are transmitted by different vectors. 6. Host
      characteristics (age/sex) were found to influence infection rates but not
      recovery rates, and their influence on infection rates was also dependent on
      parasite species: P. relictum infection rates varied with host age, whilst P.
      circumflexum infection rates varied with host sex. 7. Our analyses reveal that
      transmission of endemic avian malaria is a result of complex interactions between
      biotic and abiotic components that can operate on small spatial scales and
      demonstrate that knowledge of the drivers of spatial and temporal heterogeneity
      in disease transmission will be crucial for developing accurate epidemiological
      models and a thorough understanding of the evolutionary implications of
      pathogens.

PMID- 21848865
TI  - Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission,
      and induce neuronal injury markers in striatum.
AB  - The neurological effects of organophosphate (OP) pesticides, commonly used on
      foods and in households, are an important public health concern. Furthermore,
      subclinical exposure to combinations of organophosphates is implicated in Gulf
      War illness. Here, we characterized the effects of the broadly used insecticide
      chlorpyrifos (CPF) on dopamine and glutamatergic neurotransmission effectors in
      corticostriatal motor/reward circuitry. CPF potentiated protein kinase A (PKA)
      dependent phosphorylation of the striatal protein dopamine- and cAMP-regulated
      phosphoprotein of M(r) 32 kDa (DARPP-32) and the glutamate receptor 1 (GluR1)
      subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA
      when administered systemically. This correlated with enhanced glutamate release
      from cortical projections in rat striatum. Similar effects were induced by the
      sarin congener, diisopropyl fluorophosphate, alone or in combination with the
      putative neuroprotectant, pyridostigmine bromide and the pesticide N,N-diethyl
      meta-toluamide (DEET). This combination, meant to mimic the neurotoxicant
      exposure encountered by veterans of the 1991 Persian Gulf War, also induced
      hyperphosphorylation of the neurofibrillary tangle-associated protein tau.
      Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination,
      also increased the aberrant activity of the protein kinase, Cdk5, as indicated by
      conversion of its activating cofactor p35 to p25. Thus, consistent with recent
      findings in humans and animals, organophosphate exposure causes dysregulation in
      the motor/reward circuitry and invokes mechanisms associated with neurological
      disorders and neurodegeneration.

PMID- 21848866
TI  - Adipokines and thrombosis.
AB  - 1. Obesity is a major risk factor for cardiovascular disease. An increased body
      mass index (BMI) is associated with venous thromboembolism, myocardial
      infarction, stroke and stent thrombosis after percutaneous interventions. Studies
      in mouse models of obesity and induced arterial or venous thrombosis have
      provided insights into the mechanisms involved. 2. In addition to elevated
      circulating levels of fibrinogen, factor VII and plasminogen activator inhibitor
      (PAI)-1, changes in platelet biology and function may underlie the increased
      (athero) thrombotic risk in obesity. These include elevated platelet counts, an
      increase in mean platelet volume, an increased platelet aggregatory response to
      agonists and a reversible resistance to the anti-aggregatory effects of nitric
      oxide and prostacyclin I(2) . 3. Specific adipokines mediate the prothrombotic
      state in obesity. Of these, leptin enhances both arterial and venous thrombosis
      by promoting platelet adhesion, activation and aggregation. Leptin also induces
      tissue factor expression by human neutrophils and other cells. C-Reactive protein
      enhances the formation of monocyte-platelet aggregates and also promotes P
      selectin expression and platelet adhesion to endothelial cells. Further, the
      adipose tissue is a significant source of tissue factor and PAI-1. Conversely,
      the circulating levels of adiponectin, a hormone that exerts vasculoprotective,
      anti-atherosclerotic and antithrombotic effects, are reduced in obese
      individuals. 4. A better understanding of the interactions of the adipose tissue
      with circulating and vascular cells and the dissection of the mechanisms linking
      adipokines to arterial and venous thrombosis may identify obese individuals at
      particularly high cardiovascular risk and indicate promising vasculoprotective
      and therapeutic targets.

PMID- 21848867
TI  - Presynaptic muscarinic and adenosine receptors are involved in 2 Hz-induced train
      of-four fade caused by antinicotinic neuromuscular relaxants in the rat.
AB  - 1. Train-of-four fade (TOF(fade) ) is a clinically useful parameter to monitor
      the degree of block of neuromuscular transmission in curarized patients.
      Experimentally, TOF(fade) has been attributed to the blockade of facilitatory
      nicotinic receptors on motor nerve terminals. There is less information regarding
      the involvement of coexistent presynaptic receptors (e.g. muscarinic M(1) and
      M(2) , adenosine A(1) and A(2A) ) in the TOF(fade) produced by antinicotinic
      agents. 2. In the present study, we evaluated the TOF(fade) caused by
      antinicotinic neuromuscular relaxants (hexamethonium, d-tubocurarine, vecuronium
      and rocuronium) as the ratio of the muscle tension produced in the rat diaphragm
      by the fourth to the first stimulus (T(4) /T(1) ) of a train-of-four stimuli
      delivered to the phrenic nerve trunk at a frequency of 2 Hz. 3. All antinicotinic
      agents, except hexamethonium, decreased the amplitude of muscle tension during
      the first stimulus. Hexamethonium, (5.47 mmol/L), d-tubocurarine- (1.1 MUmol/L),
      vecuronium (4.7 MUmol/L)- and rocuronium (9.8 MUmol/L)-induced TOF(fade) was
      attenuated by 10 nmol/L pirenzepine (an M(1) receptor antagonist), 1 MUmol/L
      methoctramine (an M(2) receptor antagonist) and 2.5 nmol/L 1,3-dipropyl-8
      cyclopentylxanthine (an A(1) receptor antagonist). Blockade of the A(2A) receptor
      with 10 nmol/L ZM241385 partially reversed the TOF(fade) induced by d
      tubocurarine, vecuronium and rocuronium, but not that caused by the 'pure'
      neuronal nicotinic receptor antagonist hexamethonium, unless one increased the
      concentration of ZM241385 to 50 nmol/L. 4. The data indicate that presynaptic
      M(1) , M(2) , A(1) and A(2A) receptors play a role in neuromuscular TOF(fade)
      caused by antinicotinic neuromuscular relaxants. Such interplay depends on
      adenosine tonus and on the affinity of neuromuscular blocking agents for neuronal
      versus muscular nicotinic receptors.

PMID- 21848868
TI  - Two high linolenic mutants of Arabidopsis thaliana contain megabase-scale genome
      duplications encompassing the FAD3 locus.
AB  - Understanding the quantitative control of fatty acid desaturation during the
      biosynthesis of seed storage oil has become a priority area for research, as a
      consequence of its importance for both human health and the substitution of
      mineral oil for industrial applications. We have analysed the genome structure of
      two mutants in Arabidopsis thaliana that show substantially elevated content of
      the omega-3 polyunsaturated fatty acid linolenic acid in their seed oil. In one,
      rfc4, sequences totalling approximately 2 Mb from chromosome 2 have been
      duplicated and inserted into chromosome 3. In the other mutant, ife, chromosome 2
      sequences totalling approximately 1.4 Mb have been duplicated and inserted into a
      linked position. In both cases, the duplications encompass the FAD3 locus, which
      encodes the linoleate desaturase responsible for the biosynthesis of linolenic
      acid for accumulation in seed storage oil. The results show that mutagens such as
      fast neutrons (used for the induction of rfc4) and T-DNA (used for the induction
      of ife, which is not linked to the T-DNA present in the line) can result in the
      duplication of very large genome segments. They also show that increasing the
      dosage of the FAD3-containing genomic region results in an increase in the
      linolenic acid content of seed oil. Consequently, screening methods for
      duplication of FAD3 orthologues in oil crops may be an appropriate approach for
      the identification of germplasm for breeding varieties with increased proportions
      of linolenic acid in the oil that they produce.

PMID- 21848869
TI  - Hidden prenatal malnutrition in the rat: role of beta1-adrenoceptors on synaptic
      plasticity in the frontal cortex.
AB  - Moderate reduction in the protein content of the mother's diet (hidden
      malnutrition) does not alter body and brain weights of rat pups at birth, but
      leads to dysfunction of neocortical noradrenaline systems together with impaired
      long-term potentiation and visuo-spatial memory performance. As beta1
      adrenoceptors and downstream protein kinase signaling are critically involved in
      synaptic long-term potentiation and memory formation, we evaluated the beta1
      adrenoceptor density and the expression of cyclic-AMP dependent protein kinase,
      calcium/calmodulin-dependent protein kinase and protein kinase Fyn, in the
      frontal cortex of prenatally malnourished adult rats. In addition, we also
      studied if beta1-adrenoceptor activation with the selective beta1 agonist
      dobutamine could improve deficits of prefrontal cortex long-term potentiation
      presenting these animals. Prenatally malnourished rats exhibited half of beta1
      adrenoceptor binding, together with a 51% and 65% reduction of cyclic AMP
      dependent protein kinase alpha and calcium/calmodulin-dependent protein kinase
      alpha expression, respectively, as compared with eutrophic animals.
      Administration of the selective beta1 agonist dobutamine prior to tetanization
      completely rescued the ability of the prefrontal cortex to develop and maintain
      long-term potentiation in the malnourished rats. Results suggest that under
      expression of neocortical beta1-adrenoceptors and protein kinase signaling in
      hidden malnourished rats functionally affects the synaptic networks subserving
      prefrontal cortex long-term potentiation. beta1-adrenoceptor activation was
      sufficient to fully recover neocortical plasticity in the PKA- and
      calcium/calmodulin-dependent protein kinase II-deficient undernourished rats,
      possibly by producing extra amounts of cAMP and/or by recruiting alternative
      signaling cascades.

PMID- 21848870
TI  - Randomised clinical trial: pregabalin attenuates experimental visceral pain
      through sub-cortical mechanisms in patients with painful chronic pancreatitis.
AB  - BACKGROUND: Pregabalin has a broad spectrum of analgesic and antihyperalgesic
      activity in both basic and clinical studies. However, its mechanisms and sites of
      action have yet to be determined in humans. AIMS: To assess the antinociceptive
      effect of pregabalin on experimental gut pain in patients with visceral
      hyperalgesia due to chronic pancreatitis and to reveal putative changes in
      corresponding central pain processing as assessed by evoked brain potentials.
      METHODS: Thirty-one patients were randomly assigned to receive increasing doses
      of pregabalin or placebo for three consecutive weeks. Perceptual thresholds to
      electrical stimulation of the sigmoid with recording of corresponding evoked
      brain potentials were obtained at baseline and study end. The brain source
      localisations reflecting direct neuronal activity were fitted by a five-dipole
      model projected to magnetic resonance imaging of the individuals' brains.
      RESULTS: As compared to placebo, pregabalin significantly increased the pain
      threshold to electrical gut stimulation from baseline (P=0.02). No differences in
      evoked brain potential characteristics were seen, neither after pregabalin nor
      placebo treatment (all P>0.05). In agreement with this, brain source locations
      remained stable during study treatment (all P>0.05). CONCLUSION: Pregabalin was
      superior to placebo for attenuation of experimental visceral pain in chronic
      pancreatitis patients. We suggest its antinociceptive effects to be mediated
      primarily through sub-cortical mechanisms.

PMID- 21848871
TI  - Testicular gametogenic and steroidogenic activities in chlorpyrifos insecticide
      treated rats: a correlation study with testicular oxidative stress and role of
      antioxidant enzyme defence systems in Sprague-Dawley rats.
AB  - The present works examined an adverse effect of chlorpyrifos insecticide on
      testes and lipid peroxidation at low doses (5 mg-10 mg kg(-1) body weight) and
      the role of antioxidant enzymes systems at higher doses (20-30 mg kg(-1) body
      weight) in albino rats. At low doses, reduction in plasma levels of testosterone
      and FSH and LH hormones along with the significant shrinkage of seminiferous
      tubules and gametogenic changes in germ cells were noticed. But these changes
      were restored with the revival of serum testosterone, FSH and LH along with
      regression of testis at higher doses. Similarly, level of testicular lipid
      peroxidation was elevated, whereas levels of antioxidant enzymes (superoxide
      dismutase, catalase and glutathione peroxidase) and steroidogenic enzymes
      activities (Delta(5) , 3beta-hydroxysteroid dehydrogenase and 17beta
      hydroxysteroid dehydrogenase) were reduced significantly at low doses. But, rat
      testes showed a significant decrease in lipid peroxidation and concomitant
      increase in antioxidant enzymes and steroidogenic enzymes activities at higher
      doses. Results showed that at higher doses of chlorpyrifos treatments, rat testes
      were shown to trigger their natural defence mechanism which became operative
      possibly through corrective measure of synthesis of antioxidant defence enzymes
      and steroidogenic enzymes and pituitary gonadotrophins hormone feedback
      mechanisms.

PMID- 21848872
TI  - Cryopreservation of human sperm: efficacy and use of a new nitrogen-free
      controlled rate freezer versus liquid nitrogen vapour freezing.
AB  - Preservation of spermatozoa is an important aspect of assisted reproductive
      medicine. The aim of this study was to investigate the efficacy and use of a
      recently developed liquid nitrogen and cryogen-free controlled rate freezer and
      this compared with the classical liquid nitrogen vapour freezing method for the
      cryopreservation of human spermatozoa. Ten patients entering the IVF programme
      donated semen samples for the study. Samples were analysed according to the World
      Health Organization guidelines. No significant difference in total sperm motility
      after freeze-thawing between the new technique and classical technique was
      demonstrated. The advantage of the new freezing technique is that it uses no
      liquid nitrogen during the freezing process, hence being safer to use and clean
      room compatible. Investment costs are higher for the apparatus but running costs
      are only 1% in comparison with classical liquid nitrogen freezing. In conclusion,
      post-thaw motility of samples frozen with the classical liquid nitrogen vapour
      technique was comparable with samples frozen with the new nitrogen-free freezing
      technique. This latter technique can thus be a very useful asset to the sperm
      cryopreservation laboratory.

PMID- 21848873
TI  - Hip joint pain in spastic dislocation.

PMID- 21848874
TI  - Hip joint pain in spastic dislocation: aetiological aspects.
AB  - AIM: Children with severe forms of cerebral palsy (CP) are at high risk of hip
      joint displacement. Various studies have found that the pain from affected joints
      occurs in 40 to 84% of studied individuals. The purpose of this study was to
      establish a correlation between the density of nociceptors localized in selected
      areas of the spastic dislocated hip joint and clinical evidence of hip joint pain
      in children with CP. METHOD: Nineteen samples of articular capsule and 19 samples
      of teres ligaments, collected during open hip joint reduction from 19 non
      ambulatory children with spastic CP (Gross Motor Function Classification System
      level V; mean age 9y 6mo; 10 males, nine females), were studied. Pain was
      assessed using the numeric rating scale completed by caregivers. The density of
      nociceptive fibres was compared between the children with painful and children
      with painless hip joints, using S-100 and substance P monoclonal antibodies.
      RESULTS: The presence of S-100 protein and substance P were significantly
      increased (p=0.024 and p=0.02 respectively) in the children with painful hip
      joints. There were significantly positive correlations between the intensity of
      pain and the density of nerve fibres with S-100 protein (teres ligament, p=0.001;
      joint capsule, p=0.032) as well as substance P (teres ligament, p=0.001).
      INTERPRETATION: Direct and indirect inflammatory factors, present in dislocated
      hip joints with cartilage damage in children with spastic CP, lead to hip joint
      sensitization.

PMID- 21848875
TI  - What price a diagnosis?

PMID- 21848876
TI  - Return to autumn and interesting obstetrics and gynecology.

PMID- 21848877
TI  - A hot topic revisited.

PMID- 21848878
TI  - Microarray as a first genetic test in global developmental delay: a cost
      effectiveness analysis.
AB  - AIM: Microarray technology has a significantly higher clinical yield than
      karyotyping in individuals with global developmental delay (GDD). Despite this,
      it has not yet been routinely implemented as a screening test owing to the
      perception that this approach is more expensive. We aimed to evaluate the effect
      that replacing karyotype with array-based comparative genomic hybridization
      (aCGH) would have on the total cost of the workup for GDD. METHOD: We evaluated
      the cost-effectiveness of aCGH compared with karyotyping by retrospectively
      analysing the cost of workup in a cohort of 114 children (69 males; 45 females)
      representing a consecutive series of children diagnosed with GDD. RESULTS: The
      average increase in cost if aCGH had been performed instead of karyotyping as a
      first test was $442 per individual when performed by a private company (98%
      confidence interval $238-604). In contrast, $106 (98% confidence interval -$17 to
      $195) would have been saved if aCGH was performed locally in a laboratory already
      possessing the required technology. The incremental cost per additional diagnosis
      was estimated to be $12,874 if aCGH was performed in a private laboratory, but
      <$1379 if performed locally. (Costs reported in Canadian dollars, using 2010
      prices.) INTERPRETATION: aCGH would be cost-effective as a first genetic test in
      the clinical evaluation of individuals with GDD.

PMID- 21848880
TI  - Anticoagulating obese patients in the modern era.
AB  - The prevalence of obesity has increased substantially over recent years.
      Clinicians are increasingly being challenged with making uncertain anticoagulant
      dosing decisions, as the optimal dosing strategy for most anticoagulants in the
      obese patient population remains unknown. Research published to date suggests
      that the clearance of anticoagulants increases with weight. As obesity is
      associated with an increased risk of venous thromboembolism and arterial disease,
      there is an urgent need to establish appropriate anticoagulation regimens for
      this patient group. Research studies applying the method of pharmacokinetic
      pharmacodynamic modelling and simulation could establish an appropriate evidence
      base and provide direction and reassurance to prescribing clinicians.

PMID- 21848879
TI  - Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease.
AB  - Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia
      was studied using a novel ACS assessment tool and investigational biomarkers.
      Twelve participants were randomized (mean age 17.3 years) before early study
      termination. Dexamethasone decreased duration of hospitalization for ACS by 20.8
      h compared to placebo (P = 0.024). Rebound pain occurred in both groups (3
      dexamethasone versus 1 placebo). Overall, dexamethasone decreased the leucocyte
      activation biomarker, sL-selectin; however, participants with rebound pain had
      higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS
      assessment tool was feasibly applied, and sL-selectin is a promising biomarker of
      ACS therapy.

PMID- 21848881
TI  - Salvage therapy of autoimmune thrombocytopenic purpura revealing non-Hodgkin
      lymphoma by the thrombopoietin receptor agonist romiplostim.

PMID- 21848884
TI  - Comparative study of gene expression in patients with varicocele by microarray
      technology.
AB  - The aim of the present study was to evaluate gene expression profile by
      microarray technology and validation by real-time PCR in paired samples of
      testicular biopsies (pre-surgery and post-surgery) in two patients with
      varicocele. The microarray analysis showed increased expression levels after
      surgery in 215 and 52 genes in patient 1 and 2, respectively, as well as
      decreased expression levels in 65 genes in patient 1 and 358 genes in patient 2.
      Real-time PCR confirmed the differential expression of the five selected genes:
      MT1M, PHLDA1 and INSL3 had decreased expression levels and CCIN and PRM2
      increased expression levels compared with pre-surgery biopsies. In conclusion,
      both techniques showed decreased expression levels of genes involved in stress
      situations associated with varicocele and increased expression levels of genes
      involved in normal function of spermatogenesis.

PMID- 21848883
TI  - VcR-CVAD induction chemotherapy followed by maintenance rituximab in mantle cell
      lymphoma: a Wisconsin Oncology Network study.
AB  - Intensive chemotherapy regimens are not feasible in many adults with mantle cell
      lymphoma (MCL). We sought to build upon our previous experience with a non
      intensive regimen, modified R-hyperCVAD chemotherapy (rituximab,
      cyclophosphamide, vincristine, doxorubicin, dexamethasone) with maintenance
      rituximab (MR), by the incorporation of bortezomib (VcR-CVAD) and the extension
      of MR beyond 2 years. Patients with previously untreated MCL received VcR-CVAD
      chemotherapy every 21 d for six cycles. Patients achieving at least a partial
      response to induction chemotherapy received rituximab consolidation (375 mg/m(2)
      * 4 weekly doses) and MR (375 mg/m(2) every 12 weeks * 20 doses). The primary end
      points were overall and complete response (CR), and secondary endpoints were
      progression-free (PFS) and overall survival (OS). Thirty patients were enrolled,
      with a median age of 61 years. All patients had advanced stage disease, and 60%
      had medium/high MCL International Prognostic Index risk factors. A CR or
      unconfirmed CR was achieved in 77% of patients. After a median follow-up of 42
      months, the 3-year PFS and OS were 63% and 86%, respectively. The observed 3-year
      PFS and OS with VcR-CVAD in MCL were comparable to reported outcomes with more
      intensive regimens. A cooperative group trial (E1405) is attempting to replicate
      these promising results.

PMID- 21848882
TI  - A comparison of immune reconstitution and graft-versus-host disease following
      myeloablative conditioning versus reduced toxicity conditioning and umbilical
      cord blood transplantation in paediatric recipients.
AB  - Immune reconstitution appears to be delayed following myeloablative conditioning
      (MAC) and umbilical cord blood transplantation (UCBT) in paediatric recipients.
      Although reduced toxicity conditioning (RTC) versus MAC prior to allogeneic stem
      cell transplantation is associated with decreased transplant-related mortality,
      the effects of RTC versus MAC prior to UCBT on immune reconstitution and risk of
      graft-versus-host disease (GVHD) are unknown. In 88 consecutive paediatric
      recipients of UCBT, we assessed immune cell recovery and immunoglobulin
      reconstitution at days +100, 180 and 365 and analysed risk factors associated
      with acute and chronic GVHD. Immune cell subset recovery, immunoglobulin
      reconstitution, and the incidence of opportunistic infections did not differ
      significantly between MAC versus RTC groups. In a Cox model, MAC versus RTC
      recipients had significantly higher risk of grade II-IV acute GVHD [Hazard Ratio
      (HR) 6.1, P = 0.002] as did recipients of 4/6 vs. 5-6/6 HLA-matched UCBT (HR 3.1,
      P = 0.03), who also had significantly increased risk of chronic GVHD (HR 18.5, P
      = 0.04). In multivariate analyses, MAC versus RTC was furthermore associated with
      significantly increased transplant-related (Odds Ratio 26.8, P = 0.008) and
      overall mortality (HR = 4.1, P = 0.0001). The use of adoptive cellular
      immunotherapy to accelerate immune reconstitution and prevent and treat
      opportunistic infections and malignant relapse following UCBT warrants further
      investigation.

PMID- 21848885
TI  - Aneuploidy rate in spermatozoa of selected men with severe teratozoospermia.
AB  - The aim of this study was to evaluate the incidence of spermatic aneuploidies in
      men with severe teratozoospermia and to determine an eventual relation between
      aneuploidies and a specific morphology of spermatozoa. Fluorescence in situ
      hybridisation (FISH) using a probe cocktail containing the alpha satellite for
      the centromeric region of chromosome X, Y and 18 was performed on decondensed
      spermatozoa from fresh ejaculates of thirty patients with severe teratozoospermia
      (abnormal forms >80%) and 15 fertile men with normal semen profiles. The mean
      frequency of teratozoospermia in patients was 91 +/- 6.99%. There was
      statistically a significantly increased frequency of 1818, XY, XX and YY disomies
      in sperm with severe teratozoospermia compared with normal sperm (1.24% versus
      0.08%, 1.42% versus 0.31%, 1.13% versus 0.19% and 1.11% versus 0.24%,
      respectively, P < 0.001 in all comparisons). The rate of total diploidy was
      significantly increased in patients compared with controls (1.46% versus 0.16%, P
      < 0.001). There was a correlation between macrocephalic spermatozoa and diploidy
      (r = 0.37, P < 0.05). Our data add further evidence that patients with severe
      teratozoospermia have an increased sperm aneuploidy rate and that this is
      particularly high in macrocephalic spermatozoa; FISH analysis on sperm could help
      to improve risk assessment and reproductive counselling in these individuals who
      are frequently candidates for intracytoplasmic sperm injection (ICSI) as a
      treatment of their infertility, as the use of ICSI has created consequential
      debate concerning the genetic risk for the offspring.

PMID- 21848886
TI  - Herpes virus infected spermatozoa following density gradient centrifugation for
      IVF purposes.
AB  - Studies have documented the presence of herpes viruses in semen. The aim of our
      study was to determine whether they persist in semen samples following two
      density gradient centrifugation for IVF purposes. Semen samples were collected
      from 109 men seeking fertility evaluation, prior to IVF treatment. Routine semen
      analysis was performed according to WHO guidelines. Each sample was treated in a
      two-density gradient centrifugation using PureSperm (PS). Both untreated and
      treated samples were screened for the presence of herpes viruses, using PCR.
      Kruskal-Wallis, chi-square and binomial statistical tests were used; P <= 0.05
      was considered statistically significant. No statistically significant
      associations were observed between semen parameters and viral presence. Viral DNA
      was detected in 54% of semen samples: HSV1/2 in 32 samples, EBV in 49, CMV in 47,
      HHV6 in 9, HHV7 in 4 and VZV in none. PS gradient failed to remove CMV in 89.36%,
      HSV1/2 in 59.38% and EBV in 22.45% of samples, while HHV6 and 7 were completely
      removed. Especially HSV1/2 and CMV seem to persist even following PS treatment.
      These observations indicate the possible risk of oocyte becoming infected during
      insemination, by IVF or intracytoplasmic sperm injection, with unknown sequelae.
      Further studies are required to determine whether any correlation exists between
      their presence, implantation rate and the outcome of pregnancy.

PMID- 21848887
TI  - Relationships between seminal plasma arginase activity and spermatological
      parameters in rams.
AB  - This study was conducted to evaluate the correlation between seminal plasma
      arginase activity and spermatological parameters in rams. In this study, five
      fertility-proven Awassi rams were used as material. Six ejaculates were collected
      from each ram by an artificial vagina. Spermatological parameters (semen volume,
      mass activity, sperm motility and concentration and abnormal sperm rate) were
      immediately determined in each ejaculate. For enzyme assay, the semen samples
      were centrifuged and stored at -20  degrees C for the analysis of arginase
      activity. The average seminal plasma arginase activity was 0.61 +/- 0.20 U (mg
      protein)(-1) . There was a positive correlation between arginase activity and
      semen volume (r = 0.412, P < 0.05), semen mass activity (r = 0.610, P < 0.01),
      sperm motility (r = 0.447, P < 0.05) and sperm concentration (r = 0.808, P <
      0.01). However, there was a negative correlation between arginase activity and
      abnormal sperm rate (r = -0.424, P < 0.05). In conclusion, this study clearly
      suggests that there is a significant correlation between seminal plasma arginase
      activity and spermatological parameters. In light of these results, seminal
      plasma arginase activity may be a biochemical criterion for determining sperm
      quality besides classical semen analysis parameters in rams.

PMID- 21848888
TI  - Secondary prophylaxis with warfarin for recurrent thrombosis in a patient with
      Glanzmann thrombasthenia and F5 G1691A.

PMID- 21848889
TI  - Autologous stem cell transplantation remains beneficial for patients relapsing
      after R-CHOP chemotherapy and who respond to salvage chemotherapy.

PMID- 21848890
TI  - Variant alleles of cytokine genes influence risk and clinical course of
      Langerhans cell histiocytosis.

PMID- 21848891
TI  - Irreversible pan-ERBB inhibitor canertinib elicits anti-leukaemic effects and
      induces the regression of FLT3-ITD transformed cells in mice.
AB  - Recent findings have indicated that tyrosine kinase inhibitors (TKIs) targeting
      the ERBB receptor family display anti-leukaemic effects, despite the lack of
      receptor expression on human leukaemic cells. The occurrence of activating
      mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3) in patients with
      acute myeloid leukaemia (AML) has rendered inhibition of this receptor a
      promising therapeutic target. Due to possibility of cross-reactivity, we
      investigated the effect of the irreversible pan-ERBB inhibitor canertinib (CI
      1033) on leukaemic cells expressing FLT3. The drug had anti-proliferative and
      apoptotic effects on primary AML cells and human leukaemic cell lines expressing
      mutated FLT3. In several AML patient samples, a blast cell population expressing
      FLT3-internal tandem duplication (ITD) was eradicated by canertinib. Canertinib
      inhibited receptor autophosphorylation and kinase activity of both mutated and
      FLT3 ligand stimulated wildtype FLT3, leading to inhibition of the PI3-kinase and
      MAP kinase pathways. Apoptotic induction was dependent on pro-apoptotic BH3-only
      protein BCL2L11/BIM because siRNA silencing attenuated apoptosis. Moreover, the
      drug induced regression of cells expressing FLT3-ITD in a murine in vivo
      transplantation model at previously described tolerated doses. These results
      indicate that canertinib, as an irreversible TKI, could constitute a novel
      treatment regimen in patients with mutated or overexpressed FLT3.

PMID- 21848892
TI  - Female acne - a different subtype of teenager acne?
AB  - Above all, acne is considered an adolescent affection. However, in literature as
      in daily life, female acne is becoming more and more common. According to the
      articles that cover this subject, the prevalence is estimated from 40% to 50%.
      The objective of our work was to make an overview of new data about female acne
      at the clinical and epidemiological level to be precise if female acne has to be
      considered as a subtype of acne different from teenager acne. This review shows
      that the most frequently recognized age when speaking about female acne is 25
      years old. Most commonly it is a light to moderate acne that mainly affects the
      face. Two clinical forms can be identified: an inflammatory form, the most
      frequent, made up of papulo-pustules and nodules on the lower part of the face
      and a retentional form made up of blackheads and micro cysts with
      hyperseborrhoea. Concerning its evolution, it is characterized by three subtypes
      of which two are predominant: the most frequent form called 'continue acne' from
      adolescence to adult age and the less frequent form called 'late onset acne' that
      starts after 25 years of age. On a physiopathological level two main hypotheses
      can be proposed. Specific global assessment and therapeutic algorithm would be
      necessary for female acne, which in addition, in future would have to be
      considered separately from teenagers for the evaluation of a new drug.

PMID- 21848893
TI  - Melanocytic naevi and basal cell carcinoma: is there an association?
AB  - BACKGROUND: Melanoma and basal cell carcinoma (BCC) affect similar body sites and
      share a complex relationship with sun exposure. OBJECTIVE: To establish the
      existence and magnitude of association between melanocytic naevi, the strongest
      predictors of melanoma, and BCC to give possible insights into shared pathways of
      solar ultraviolet tumourigenesis. METHODS: In a community-based longitudinal
      Australian study, detailed information was collected about sun sensitivity, and
      dermatologists assessed skin colour and counted naevi on the forearms (1986) and
      back (1992). The BCC frequency and sites were prospectively monitored until 2007.
      Multivariate logistic regression was used to assess the association of naevi on
      the forearms or on the back with the development of BCC, adjusting for other risk
      factors. RESULTS: Of 1621 study participants in 1992, 1339 (average age 49) had
      complete follow-up and 401 (30%) of these had 1202 histologically confirmed BCCs
      until 2007. After adjustment for age, gender, skin colour, naevi on the back and
      sun exposure, overall BCC risk increased significantly in those with forearm
      naevi (odds ratio: 1.5; 95% confidence intervals: 1.1-1.9). Risk of BCC
      specifically on the back was doubled in those with many (11 or more) forearm
      naevi compared with no forearm naevi (odds ratio: 2.4; 95% confidence interval:
      1.1-4.8). Naevi on the back were not associated with subsequent basal cell
      carcinoma. CONCLUSIONS: High naevus prevalence on the arms is associated with
      future BCC development.

PMID- 21848894
TI  - Efficacy of two Ni-Ti systems and hand files for removing gutta-percha from root
      canals.
AB  - AIM:   To compare the effectiveness of two Ni-Ti systems and hand files for
      removing gutta-percha and sealer from root canals. METHODOLOGY:   The root canals
      of 60 single-rooted human teeth were prepared, filled with gutta-percha and
      sealer (Pulp Canal Sealer; SybronEndo, Orange, CA, USA). Specimens were then
      divided into three groups (n=20), and root filling material was removed using
      MTwo Retreatment Files (group 1); R-Endo (group 2); K-files and Gates-Glidden
      drills (group 3). After retreatment, the efficacy of each technique was assessed
      using radiographs that were later digitized and the images analysed using AutoCAD
      2004. The percentage of residual gutta-percha was calculated for the whole canal
      as well as for the coronal, middle and apical thirds. Time required, apically
      extruded debris and the number of fractured instruments were also recorded. Data
      were statistically analysed using Kruskal-Wallis and Mann-Whitney U-tests.
      RESULTS:   All instrumentation techniques left gutta-percha and sealer remnants
      inside the root canals. Ni-Ti systems were significantly faster (P < 0.05) than
      the manual technique and significantly more effective (P < 0.05) in removing
      gutta-percha particularly from the middle and apical thirds of the root canal. R
      Endo instrumentation was significantly more effective (P < 0.05) than MTwo
      retreatment files in removing gutta-percha from the middle and apical thirds. R
      Endo instruments were associated with the least number of cases of apical
      extrusion. One MTwo instrument fractured. CONCLUSIONS:   The Ni-Ti systems were
      more effective and faster than hand files, although all techniques left gutta
      percha and sealer remnants on the root canals.

PMID- 21848895
TI  - Postoperative morbidity after fast-track laparoscopic resection of rectal cancer.
AB  - AIM: Analysis was carried out of the nature and chronological order of early
      complications after fast-track laparoscopic rectal surgery with a view to
      optimizing the short-time outcome of rectal cancer surgery. METHOD: A total of
      102 consecutive patients who underwent elective fast-track laparoscopic rectal
      cancer surgery were analysed prospectively from the Danish Colorectal Cancer
      Database supplemented by data from the medical records. We studied in detail the
      nature and chronological order of postoperative morbidity and reason for
      prolonged stay (> 5 days). RESULTS: Twenty-five patients (25%) had one or more
      complications. Surgical complications occurred in 19 patients, while six patients
      had medical complications as the primary event. Fifteen patients underwent
      reoperation, three died, and eight were readmitted within 30 days. The median
      length of stay was 5 days (range 2-42). CONCLUSION: Postoperative morbidity
      remains a significant problem in the fast-track era, even in experienced surgical
      hands. Our results suggest that besides improvement of surgical technique further
      improvement of outcome lies in early recognition and proper treatment of
      complications and the perioperative optimization of organ function.

PMID- 21848896
TI  - Current status of the treatment of acute colonic diverticulitis: a systematic
      review.
AB  - AIM: This paper addresses the current status of the treatment of acute colonic
      diverticulitis by an evidence-based review. METHOD: A systematic search in
      PUBMED, MEDLINE, EMBASE and Google scholar on colonic diverticulitis was
      performed. Diagnostic tools, randomized controlled trials, non-randomized
      comparative studies, observational epidemiological studies, national and
      international guidelines, reviews of observational studies on elective and
      emergency surgical treatment of diverticulitis, and studies of prognostic
      significance were reviewed. Criteria for eligibility of the studies were
      diagnosis and classification, medical treatment, inpatients and outpatients,
      diverticulitis in young patients, immunosuppression, recurrence, elective
      resection, emergency surgery, and predictive factors. RESULTS: Some 92
      publications were selected for comprehensive review. The review highlighted that
      computed tomography is the most effective test in the diagnosis and staging of
      acute diverticulitis; outpatient treatment can be performed for uncomplicated
      diverticulitis in patients without associated comorbidities; conservative
      treatment is aimed at those patients with uncomplicated acute diverticulitis;
      elective surgery must be done on an individual basis; laparoscopic approach for
      elective treatment of diverticulitis is appropriate but may be technically
      complex; in perforated diverticulitis, resection with primary anastomosis is a
      safe procedure that requires experience and should take into account strict
      exclusion criteria. CONCLUSION: The heterogeneity of patients with colonic
      diverticular disease means that both elective and urgent treatment should be
      tailored on an individual basis.

PMID- 21848897
TI  - A systematic review of treatment guidelines for metastatic colorectal cancer.
AB  - AIM: A systematic review of treatment guidelines for metastatic colorectal cancer
      (mCRC) was performed to assess recommendations for monoclonal antibody therapy in
      these guidelines. METHOD: Relevant papers were identified through electronic
      searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through
      manual searches of reference lists; and by searching the Internet. RESULTS: A
      total of 57 relevant guidelines were identified, 32 through electronic database
      searches and 25 through the website searches. The majority of guidelines were
      published between 2004 and 2010. The country publishing the most guidelines was
      the USA (12), followed by the UK (10), Canada (eight), France (eight), Germany
      (three), Australia (two), Spain (two) and Italy (one). In addition, eight
      European and three international guidelines were identified. As monoclonal
      antibody therapy for mCRC was not introduced until 2004, no firm recommendations
      for monoclonal antibody therapy were made in guidelines published between 2004
      and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007
      and evolved as more data became available. The most recent international,
      European and US guidelines recommend combination chemotherapy with the addition
      of a monoclonal antibody for the first-line treatment of mCRC. Second-line
      treatment depends on the first-line regimen used. For chemoresistant mCRC,
      cetuximab or panitumumab are recommended as monotherapy in patients with wild
      type KRAS tumours. CONCLUSION: The study indicates that recent treatment
      guidelines have recognized the role of monoclonal antibodies in the management of
      mCRC, and that treatment guidelines should be updated in a timely manner to
      reflect the most recently available data.

PMID- 21848898
TI  - Anti tumour necrosis factor as risk factor for free perforations in Crohn's
      disease? A case-control study.
AB  - AIM: Although the occurrence of intestinal perforation in Crohn's disease (CD) is
      rare, clinical observation has led to the question whether anti tumour necrosis
      factor (TNF) treatment is a risk factor for free perforation. The aim of this
      study was to investigate the possible relation between anti-TNF treatment and
      occurrence of free perforation, defined as intestinal perforations leading to
      emergency surgery. METHOD: In this case-control study, all emergency operation
      reports from the period 1999-2009 of patients diagnosed with CD were checked for
      the presence of free perforation. These cases were compared with a sixfold larger
      control group derived from our CD patient database. Cases and controls were
      matched for age, gender, Montreal classification and surgical stage to ensure
      equal disease severity. Cases and controls were then compared regarding previous
      or current exposure to anti-TNF treatment. RESULTS: Thirteen patients underwent
      emergency surgery for spontaneous free perforation. Eight (62%) had been treated
      with anti-TNF within 5 months before the perforation. In the 78 matched controls,
      29 (37%) had been or were still treated with anti-TNF. The odds for a free
      perforation adjusted for known confounders in two separate regression analyses
      were significantly higher in anti-TNF treated CD patients, albeit with a large
      confidence interval (OR 4.1, 95% CI: 1.1-16.0; and OR 23.0, 95% CI 2.2-238.5).
      CONCLUSION: This study showed a higher occurrence of free perforations in CD
      patients with anti-TNF therapy compared with those without anti-TNF therapy.
      Patients with CD and anti-TNF treatment showing acute abdominal pain must be
      suspected of this complication.

PMID- 21848899
TI  - Apoptotic proteins as prognostic markers and indicators of radiochemosensitivity
      in stage II/III rectal cancers.
AB  - AIM: The expression of pro-apoptotic (Bax) and anti-apoptotic (mutated p53, Bcl
      2, Bclxl) proteins was determined retrospectively using immunohistochemistry in
      pre-treatment biopsy samples from patients with rectal cancer treated with or
      without preoperative chemoradiation to investigate their role as prognostic
      markers and indicators of radiochemosensitivity. METHOD: Biopsy samples from 67
      patients operated for stage II/III rectal cancer and enrolled in an active follow
      up programme were examined 8-10 years after surgery. Thirty-three had been
      treated with immediate surgery followed, in selected cases, by adjuvant
      postoperative chemoradiation. Thirty-four had preoperative chemoradiation.
      Immunohistochemical staining was carried out using an automated immunostainer on
      sections of paraffin-embedded tissue. RESULTS: Independent prognostic factors for
      rectal cancer death were pN status (hazard ratio 3.82; 95% CI 1.67-8.73) and a
      high level of Bclxl positivity (hazard ratio 4.75; 95% CI 2.10-10.72) according
      to multivariate regression analysis by stepwise selection. Bax expression was
      associated with downstaging and higher survival in irradiated patients (P =
      0.0004). CONCLUSION: Pretreatment evaluation of apoptotic Bax and anti-apoptotic
      Bclxl factors in biopsy samples of stage II/III rectal cancers may be helpful in
      selecting tumours that will respond to chemoradiation or in identifying patients
      who will have limited benefit from chemoradiation and should therefore be
      selected for a more aggressive systemic regimen.

PMID- 21848900
TI  - HLA-G on peripheral blood CD4(+)  T lymphocytes: a potential predictor for acute
      renal rejection.
AB  - HLA-G Expression in grafts and serum has been shown to improve graft acceptance.
      However, its expression on peripheral blood lymphocytes (PBLs) during acute
      rejection (AR) remains unknown. In this study, we serially monitored HLA-G
      expression on CD4(+) and CD8(+) PBLs of 66 recipients undergoing renal
      transplantation using flow cytometry at different time points before and after
      transplantation, as well as during AR episode. In stable recipients, HLA-G
      expression on CD4(+) PBLs declined during the first week after transplantation
      and increased continuously with immunosuppressive therapy. Then, expression
      declined gradually after 1 month and remained at a higher level compared with
      pretransplantation. When AR occurred, HLA-G expression decreased significantly
      compared with the stable level. In three recipients suffering from recurrent
      rejection, it remained at a low level despite impact immunosuppressive treatment.
      With mix lymphocyte assay, HLA-G(+) CD4(+) T cells showed inhibitory role on
      proliferation of peripheral blood mononuclear cell. HLA-G expression on CD8(+)
      PBLs was almost undetectable at different time points in the recipients and
      healthy controls. Our results suggest that HLA-G on CD4(+) PBLs might provide a
      potential marker for the early diagnosis of renal AR and for the
      immunosuppressive status of recipients.

PMID- 21848901
TI  - Characteristics of low-density and high-density lipoprotein subclasses in
      pediatric renal transplant recipients.
AB  - Renal transplant recipients often suffer from dyslipidemia which is one of the
      principal risk factors for cardiovascular disease. This study sought to determine
      characteristics of high-density lipoprotein (HDL) and low-density lipoprotein
      (LDL) particles and their associations with carotid intima-media thickness (cIMT)
      in a group of pediatric renal transplant recipients. We also examined the
      influence of immunosuppressive therapy on measured LDL and HDL particle
      characteristics. HDL size and subclass distribution were determined using
      gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)
      cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin
      magnesium precipitation method in 21 renal transplant recipients and 32 controls.
      Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P <
      0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL-C (P < 0.01)
      and sdLDL-apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a
      significant predictor of increased cIMT (P < 0.05). Patients treated with
      cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P <
      0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant
      recipients have impaired distribution of HDL and LDL particles. Changes in the
      proportion of small-sized HDL particles are significantly associated with cIMT.
      Advanced lipid testing might be useful in evaluating the effects of
      immunosuppressive therapy.

PMID- 21848902
TI  - Long-term follow up for anti-HLA donor specific antibodies postrenal
      transplantation: high immunogenicity of HLA class II graft molecules.
AB  - Tauhe clinical significance of de novo post-transplant anti-HLA donor-specific
      antibodies (DSA) was evaluated using 4241 serum samples collected between 2000
      and 2007 from 597 renal transplant recipients. Patients transplanted before
      December 1996 (n = 77) were included in the historic group and those transplanted
      thereafter (n = 520) were included in the study group. All recipients were
      negative for DSA before transplantation (Tx). Post-Tx, de novo DSA were detected
      in 92/597 (15.4%) patients, while 196 had third party anti-HLA antibodies (DSA
      negative). DSA were more frequent in the historic group (33.8%) compared with the
      study group (12.7%) (P < 0.001). Anti-HLA class-II DSA predominated in both
      groups (84.6% vs. 69.7%). Recipients of HLA class II-incompatible grafts
      developed DSA more frequently than those receiving HLA class II-compatible grafts
      (17.9% vs.7.9%, P = 0.003), directed mainly against HLA-DQ graft molecules
      (64/446, 14.4%). DSA production was not different between presensitized and
      nonsensitized patients (P = 0.842). Graft survival was higher in patients without
      antibodies compared with DSA-positive (log-rank test, P = 0.002) and DSA-negative
      patients (log-rank test, P = 0.002). Univariate and multivariate analysis showed
      independent association for DSA class I (HR = 31.78), DSA class II (HR = 20.92)
      and non-DSA (HR = 5.94) and graft failure. We conclude that HLA class II
      incompatible graft transplantations need careful monitoring and should be avoided
      in high immunological risk cases.

PMID- 21848903
TI  - Microvascular reactivity in response to smoking and oral antioxidants in humans.
AB  - OBJECTIVE: To investigate whether a daily intake of a moderate dose of
      antioxidants modifies the microcirculatory response to smoking, assuming a major
      influence of oxidative stress on microcirculation. METHODS: The microvascular
      response to smoking was assessed in individual capillaries by capillaroscopy
      before and after two weeks of treatment with oral antioxidants. RESULTS: Smoking
      prolonged time to peak (TtP) capillary blood flow velocity in all subjects. When
      the subjects were pre-treated with ascorbate, TtP was comparable to baseline
      values of untreated subjects. No significant effect of vitamin E was observed
      either before or after smoking. Capillary blood flow velocity increased after
      treatment with ascorbate as well as after vitamin E. However, significant
      reductions in velocity were still observed in response to smoking even after
      subjects consumed ascorbate and vitamin E (p<0.0004 and p<0.000008 respectively).
      CONCLUSIONS: This study focused on individual capillaries, and confirms that
      smoking has a very pronounced, direct and reproducible microvascular effect
      possible to demonstrate in vivo in human capillaries. Moderate intake of the
      antioxidant ascorbate clearly mitigated the effects induced by smoking. TtP after
      smoking in subjects treated with ascorbate was similar to that observed in
      untreated subjects before smoking a cigarette. Thus, oxidative stress could be
      assumed to play a role in the effects of smoking on microcirculation.

PMID- 21848904
TI  - Long-term quality of life after pregnancy-related deep vein thrombosis and the
      influence of socioeconomic factors and comorbidity.
AB  - BACKGROUND: Little is known about the long-term impact of pregnancy-related deep
      vein thrombosis (DVT) of the lower limbs. OBJECTIVES: To evaluate the long-term
      consequences of pregnancy-related DVT by assessment of self-reported, disease
      specific quality of life (QOL) and symptom severity using the Venous
      Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire,
      and to investigate the influence of socioeconomic factors and comorbidity.
      PATIENTS/METHODS: In this cross-sectional case-control study, 313 women with
      validated pregnancy-related DVT and 353 controls completed a comprehensive
      questionnaire, including the disease-specific VEINES-QOL/Sym questionnaire. After
      exclusion of DVT outside the lower limbs and missing scores, the study population
      comprised 208 patients and 347 controls. A VEINES-QOL/Sym score < the 25th
      percentile was defined as a clinically relevant reduced outcome compared with
      scores >= the 50th percentile. Predictors for low scores were identified in
      multivariate logistic regression models. RESULTS: Cases reported lower mean
      VEINES-QOL/Sym scores than controls, 45.6/45.4 vs. 52.8/52.7, respectively (P <
      0.001), and QOL among cases was still reduced compared with controls when
      adjusted for possible confounders. Low education was an independent predictor for
      both low VEINES-QOL and VEINES-Sym scores, and in addition being
      married/cohabitating predicted low VEINES-Sym scores. CONCLUSIONS: Long-term QOL
      and symptom scores as assessed with the VEINES-QOL/Sym questionnaire were lower
      in women with previous pregnancy-related DVT than in controls, and also when
      adjusted for possible confounders. By logistic regression, low education was an
      independent predictor for low scores. This supports the use of the VEINES-QOL/Sym
      questionnaire in studies on pregnancy-related DVT.

PMID- 21848905
TI  - Temoporfin (Foscan(r), 5,10,15,20-tetra(m-hydroxyphenyl)chlorin)--a second
      generation photosensitizer.
AB  - This review traces the development and study of the second-generation
      photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin through to its
      acceptance and clinical use in modern photodynamic (cancer) therapy. The
      literature has been covered up to early 2011.

PMID- 21848906
TI  - Lactobacillus plantarum AS1 binds to cultured human intestinal cell line HT-29
      and inhibits cell attachment by enterovirulent bacterium Vibrio parahaemolyticus.
AB  - AIM: Lactobacillus plantarum AS1 was incubated with HT-29 adenocarcinoma cell
      line to assess its adhesion potency and examined for its inhibitory effect on the
      cell attachment by an enterovirulent bacterium Vibrio parahaemolyticus. METHODS
      AND RESULTS: Lactobacillus plantarum AS1 attached efficiently to HT-29 cells as
      revealed by scanning electron microscopy and bacterial adhesion assay.
      Lactobacillus plantarum AS1 significantly reduced V. parahaemolyticus attached to
      HT-29 cells by competition, exclusion and displacement mode. Lactobacillus
      plantarum AS1 seems to adhere to human intestinal cells via mechanisms that
      involve different combinations of carbohydrate and protein factors on the
      bacteria and eukaryotic cell surface. CONCLUSION: Strain Lact. plantarum AS1
      inhibits the cell attachment of a pathogen V. parahaemolyticus by steric
      hindrance mechanism. Also, antibacterial factors such as bacteriocins, lactic
      acid and exopolysaccharides could be involved. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The ability to inhibit the adhesion of V. parahaemolyticus to intestinal
      cell line warrants further investigation to explore the use of probiotic strain
      Lact. plantarum AS1 in the management of gastroenteritis caused by V.
      parahaemolyticus.

PMID- 21848907
TI  - Effects of the cannabinoid antagonist SR 141716 on sexual and motor behaviour in
      receptive female rats.
AB  - 1. The aim of the present study was to investigate the effect of the cannabinoid
      antagonist/inverse agonist SR 141716 (SR) on the receptive behaviour and sexual
      motivation of female rats. 2. Partner preference, receptivity and proceptivity
      were evaluated in ovariectomized female rats primed with oestrogen and
      progesterone and administered SR (1 or 2.5 mg/kg, i.p.) 20 min prior to testing.
      3. In the partner preference test, a reduced interest in both stimulus animals (a
      sexually active male and an ovariectomized hormone-primed female) was detected in
      rats treated with SR at both doses, but no effect on preference score was
      observed. In the receptivity test, pronounced reductions in lordosis quotient,
      lordosis rating and in the percentage of receptive females were found in SR
      treated rats compared with control rats. Proceptive behaviours were not
      significantly affected by either dose of SR. 4. In addition, we explored the
      behavioural effects induced by SR in female rats using the open field test. Only
      at the higher dose (i.e. 2.5 mg/kg) did SR markedly increased grooming and
      scratching behaviour. 5. The results demonstrate the ability of SR to reduce
      female sexual receptivity, but not sexual motivation. The reduction does not seem
      strictly related to the motor alterations induced by the cannabinoid antagonist.

PMID- 21848908
TI  - Should 'mild primary hyperparathyroidism' be reclassified as 'insidious': is it
      time to reconsider?
AB  - Primary hyperparathyroidism (PHPT) is a common incidental finding on routine
      biochemical testing, affecting around 1% of the population. The majority of
      individuals will be asymptomatic at diagnosis, with no evidence of end organ
      damage, and unless individuals aged <50 years at diagnosis, they are often
      considered to have 'mild' PHPT, as they do not meet published criteria for
      parathyroidectomy (PTX). However, there is increasing evidence that 'mild' PHPT
      is associated with adverse health outcomes. Long-term observational studies
      describing the natural history of 'mild' PHPT suggest that even though
      biochemistry may be relatively stable in the majority, bone mineral density (BMD)
      does decline after approximately 10 years of observation, whereas significant
      improvements in BMD are seen following PTX. Recent large European record linkage
      studies of 'mild PHPT' demonstrate significantly increased all-cause and
      cardiovascular mortality, similar to rates published for patients with PHPT who
      meet the NIH surgical criteria. 'Mild' PHPT was also associated with increased
      admissions for nonfatal cardiovascular disease, renal failure, renal stones,
      fractures, hypertension, psychiatric disease, cancer and diabetes, suggesting
      that 'insidious' PHPT may be a more appropriate description, or at least that the
      term 'mild' should be abandoned. Randomized controlled trials (RCTs) have begun
      to explore the benefits of PTX in this condition, demonstrating improvements in
      BMD and some psychiatric outcomes at approximately 2 years of follow-up. However,
      larger, adequately powered, long-term, RCTs will be required to determine whether
      PTX improves potential long-term morbidity and mortality in patients with PHPT
      who do not meet standard surgical criteria.

PMID- 21848910
TI  - Changes in TNM stage, reoperation and 131-I ablation rate during the use of newer
      methods for the preoperative diagnosis of differentiated thyroid carcinoma.
AB  - OBJECTIVE: To define and discuss the changes of important risk factors and TNM
      staging over the last 40 years in patients operated on for differentiated thyroid
      carcinoma (DTC), resulting from the introduction of newer sensitive diagnostic
      procedures in the preoperative evaluation of thyroid nodules. PATIENTS: We
      reviewed the medical records of 1251 patients with postoperative diagnosis of DTC
      who had undergone initial diagnosis, before surgery, at our unit, between 1971
      and 2010. According to the period of diagnosis, the patients were divided into
      four groups (I, II, III, IV) corresponding to the four decades. RESULTS: The mean
      age at diagnosis was unchanged over time for both papillary (PTC) and follicular
      thyroid cancer (FTC). A decrease in the proportion of FTC (group I vs group IV P
      < 0.01) and a concomitant increase in PTC/FTC ratio was observed particularly in
      group IV. The significant decrease in the proportion of tumour size of PTC (group
      I vs group IV, P < 0.01), the increase in the proportion of microcarcinomas, from
      22.4% in group I to 53.0% in group IV, P < 0.001, and the decrease in the number
      of cases with features of aggressiveness have changed the TNM stage towards
      stages I and II. The overall frequency of patients at high risk was significantly
      decreased, from 8.0% in group I to 1.8% in group IV. The number of patients who
      underwent reoperation for the completion of tumour resection and/or radioiodine
      therapy significantly decreased over time. CONCLUSIONS: The evaluation of thyroid
      nodules using the newer diagnostic methods was useful in identifying DTC early.
      Consequently, the reoperation and thyroid remnant ablation rates were reduced.

PMID- 21848909
TI  - Balance between somatostatin and D2 receptor expression drives TSH-secreting
      adenoma response to somatostatin analogues and dopastatins.
AB  - CONTEXT: First-line therapy for thyrotropin-secreting pituitary adenomas
      (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin
      analogues. Clinically available sst(2) -preferring analogues, octreotide and
      lanreotide, induce normalization of hormone levels in approximately 90% of
      patients and tumour shrinkage in 45%. OBJECTIVE: We evaluated somatostatin 1, 2,
      3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas,
      and the relationships between receptor expression, in vitro antiproliferative
      response and clinical data, including octreotide test and three months of therapy
      with octreotide long-acting repeatable (LAR). TSHoma cell proliferation was
      tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM
      23A760 and BIM-23A387. RESULTS: All patients showed significant TSH lowering to
      acute octreotide test, but a hormonal response to long-term treatment was
      observed in only two patients, showing a high sst(5) /sst(2) ratio. Patient 2,
      characterized by high expression of sst(2) and sst(1) and a relative lower
      expression of sst(5) , experienced tachyphylaxis after prolonged octreotide
      treatment. In vitro, the somatostatin/dopamine receptor agonist BIM-23A760 caused
      the highest antiproliferative effect among those tested. Combined treatment with
      octreotide and cabergoline displayed an additive effect of magnitude comparable
      to that of the other chimeric compound (BIM-23A387). Octreotide resistance was
      confirmed in cells isolated from the nonresponder patient, although it could be
      overcome by treatment with the chimeric compounds. CONCLUSIONS:   A high sst(5)
      /sst(2) ratio might be predictive of a positive outcome to long-term treatment
      with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D(2)
      receptor targeting might be considered as a potential tool to improve the
      response rate in octreotide-resistant tumours.

PMID- 21848911
TI  - Seminal fibronectin in fertile and infertile males.
AB  - This study aimed to assess seminal plasma fibronectin in fertile and infertile
      males. Ninety infertile males were investigated; asthenozoospermia (n = 27),
      asthenoteratozoospermia (n = 30), oligoasthenoteratozoospermia (n = 33) compared
      with 20 healthy fertile controls. They were subjected to semen analysis, seminal
      plasma fibronectin estimation by radial immune diffusion, serum testosterone (T)
      and follicle stimulating hormone (FSH) estimation by ELISA. There was significant
      increase of seminal plasma fibronectin among different infertile groups compared
      with the controls. Significant negative correlation was elicited between seminal
      fibronectin and sperm count, sperm motility grades A, B, A + B, sperm velocity,
      linear velocity, linearity index, sperm normal forms and serum T. Seminal
      fibronectin showed significant positive correlation with grade D sperm motility
      and serum FSH. ROC curve analysis discriminating controls and other infertile
      groups demonstrated criteria value of < 674 mg l(-1) (sensitivity 100% and
      specificity 96.4%). It is concluded that increased seminal fibronectin is
      associated with decreased sperm count and sperm motility.

PMID- 21848912
TI  - Antimicrobial peptides important in innate immunity.
AB  - Antimicrobial peptides are present in all walks of life, from plants to animals,
      and they are considered to be endogenous antibiotics. In general, antimicrobial
      peptides are determinants of the composition of the microbiota and they function
      to fend off microbes and prevent infections. Antimicrobial peptides eliminate
      micro-organisms through disruption of their cell membranes. Their importance in
      human immunity, and in health as well as disease, has only recently been
      appreciated. The present review provides an introduction to the field of
      antimicrobial peptides in general and discusses two of the major classes of
      mammalian antimicrobial peptides: the defensins and the cathelicidins. The review
      focuses on their structures, their main modes of action and their regulation.

PMID- 21848913
TI  - Downregulation of receptor for activated C-kinase 1 (RACK1) suppresses tumor
      growth by inhibiting tumor cell proliferation and tumor-associated angiogenesis.
AB  - By behaving as molecular hubs, scaffold proteins can assemble a large number of
      signaling molecules and organize complicated intracellular signaling networks in
      time and space. Owing to their crucial role in mediating intracellular signaling
      related to tumor cell growth and migration, recent studies have highlighted the
      relevance of scaffold proteins in human cancers and indicated that interfering
      with their expression and/or their ability to bind effector proteins can inhibit
      cancer progression. Here, we show that receptor for activated C-kinase 1 (RACK1),
      a ubiquitously expressed scaffolding protein, plays a crucial regulatory role in
      tumor growth. Using an RNA silencing approach, we found that downregulation of
      RACK1 expression in HeLa and A673 tumor cells markedly suppressed the
      proliferation and invasion of these cells in vitro and tumor development in vivo.
      Consequently, we found that significant suppression of constitutive
      phosphorylation of Akt and MAPK by RACK1 silencing may contribute to the
      inhibition of tumor growth. Moreover, RACK1 silencing significantly attenuated
      tumor-associated angiogenesis by, at least in part, inhibiting the expression of
      two critical angiogenic factors, namely vascular endothelial growth factor-B and
      fibroblast growth factor 2. The results of the present study show that RACK1 is a
      potent enhancer of tumor growth and, thus, a potential anti-cancer therapeutic
      target.

PMID- 21848915
TI  - Localized egg-cell expression of effector proteins for targeted modification of
      the Arabidopsis genome.
AB  - Targeted modification of the genome is an important genetic tool, which can be
      achieved via homologous, non-homologous or site-specific recombination. Although
      numerous efforts have been made, such a tool does not exist for routine
      applications in plants. This work describes a simple and useful method for
      targeted mutagenesis or gene targeting, tailored to floral-dip transformation in
      Arabidopsis, by means of specific protein expression in the egg cell. Proteins
      stably or transiently expressed under the egg apparatus-specific enhancer (EASE)
      were successfully localized to the area of the egg cell. Moreover, a zinc-finger
      nuclease expressed under EASE induced targeted mutagenesis. Mutations obtained
      under EASE control corresponded to genetically independent events that took place
      specifically in the germline. In addition, RAD54 expression under EASE led to an
      approximately 10-fold increase in gene targeting efficiency, when compared with
      wild-type plants. EASE-controlled gene expression provides a method for the
      precise engineering of the Arabidopsis genome through temporally and spatially
      controlled protein expression. This system can be implemented as a useful method
      for basic research in Arabidopsis, as well as in the optimization of tools for
      targeted genetic modifications in crop plants.

PMID- 21848916
TI  - Pentoxifylline to avoid radiation-induced cardiotoxicity: from NF-kappaB to
      beyond--a reply to M. Halle and P. Hall and P. Tornvall.

PMID- 21848914
TI  - Targeting glioma stem cells: a novel framework for brain tumors.
AB  - The past decade has seen a dramatic increase in stem cell research that focuses
      on glioma stem cells (GSC) and their mechanisms of action, revealing multiple
      potential targets for primary malignant brain tumors. Herein, we present a novel
      framework for considering GSC targets based on direct and indirect strategies.
      Direct strategies target GSC molecular pathways to overcome their resistance to
      radiation and chemotherapy, block their function or induce their differentiation.
      Indirect strategies target the microenvironment of the GSC, namely the
      perivascular, hypoxic and immune niches. Progress made on GSC targets is reviewed
      in detail and specific pathways are identified in context of the proposed
      framework. The potential barriers for translation to the clinical setting are
      also discussed. Overall, targeting GSC provides an unprecedented opportunity for
      revolutionary approaches to treat high-grade gliomas that continue to have a poor
      patient prognosis.

PMID- 21848917
TI  - Beyond nuclear factor kappaB in cardiovascular disease induced by radiotherapy.

PMID- 21848918
TI  - Enhanced visual perception with occipital transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS) over the occipital pole can produce an
      illusory percept of a light flash (or 'phosphene'), suggesting an excitatory
      effect. Whereas previous reported effects produced by single-pulse occipital pole
      TMS are typically disruptive, here we report the first demonstration of a
      location-specific facilitatory effect on visual perception in humans. Observers
      performed a spatial cueing orientation discrimination task. An orientation target
      was presented in one of two peripheral placeholders. A single pulse below the
      phosphene threshold applied to the occipital pole 150 or 200 ms before stimulus
      onset was found to facilitate target discrimination in the contralateral compared
      with the ipsilateral visual field. At the 150-ms time window contralateral TMS
      also amplified cueing effects, increasing both facilitation effects for valid
      cues and interference effects for invalid cues. These results are the first to
      show location-specific enhanced visual perception with single-pulse occipital
      pole stimulation prior to stimulus presentation, suggesting that occipital
      stimulation can enhance the excitability of visual cortex to subsequent
      perception.

PMID- 21848919
TI  - A systematic review to determine the effectiveness of interventions designed to
      prevent overweight and obesity in pre-adolescent girls.
AB  - Childhood overweight/obesity is recognized as an increasing health problem. The
      objective of this review was to determine the effectiveness of interventions
      designed to prevent overweight and obesity in pre-adolescent girls. The papers
      included were those studying children (must include results for girls) from
      within the 7-11 years age range from any country and ethnic background. The
      included interventions lasted at least 12 weeks and modified a combination of
      nutrition, physical activity, knowledge, attitudes or health-related behaviours
      associated with the development of childhood overweight and obesity. Effect sizes
      were calculated where possible using Cohen's classifications of small (0.2-0.5),
      medium (0.5-0.8) and large (>0.8) effect sizes. Thirty studies met the inclusion
      criteria of which four were cluster randomized controlled trials, 14 were
      randomized controlled trials, 11 were controlled trials and one was a cohort pre
      post trial. There were four weak, 11 moderate and 15 strong quality studies.
      Eleven studies were considered short term and 19 long term (>=12 months). There
      were 66 effect sizes less than 0.2, 56 categorized as low, 16 as medium and two
      as high. There is the potential for interventions aimed at pre-adolescent girls
      to reduce the risk factors associated with childhood overweight and obesity,
      although the sustainability of the effects of such interventions is less clear.

PMID- 21848920
TI  - Contribution of the amygdala, but not orbitofrontal or medial prefrontal
      cortices, to the expression of flavour preferences in marmoset monkeys.
AB  - The development of food preferences contributes to a balanced diet, and involves
      both innate and learnt factors. By associating flavour cues with the reinforcing
      properties of the food (i.e. postingestive nutrient cues and innately preferred
      tastes, such as sweetness), animals acquire individual preferences. How the brain
      codes and guides selection when the subject has to choose between different
      palatable foods is little understood. To investigate this issue, we trained
      common marmoset monkeys (Callithrix jacchus) to respond to abstract visual
      patterns on a touch-sensitive computer screen to gain access to four different
      flavoured juices. After preferences were stable, animals received excitotoxic
      lesions of either the amygdala, the orbitofrontal cortex or the medial prefrontal
      cortex. Neither the orbitofrontal nor the medial prefrontal cortex lesions
      affected pre-surgery-expressed flavour preferences or the expression of
      preferences for novel flavours post-surgery. In contrast, amygdala lesions caused
      a shift in the preferences for juices expressed pre-surgery such that, post
      surgery, juices were chosen according to their overall carbohydrate (simple
      sugars) content or 'sweetness'. Subsequent tests revealed that amygdala-lesioned
      animals only expressed juice preferences if they differed in 'sweetness'. Unlike
      controls, orbitofrontal cortex-lesioned and medial prefrontal cortex-lesioned
      animals, they were unable to display preferences between juices matched for
      'sweetness' i.e. 5% sucrose solutions aromatised with different essential oils.
      The most parsimonious explanation is that the amygdala contributes to the
      expression of food preferences based on learnt cues but not those based on an
      innate preference for sweetness.

PMID- 21848921
TI  - Intra-ventral tegmental area or intracerebroventricular orexin-A increases the
      intra-cranial self-stimulation threshold via activation of the corticotropin
      releasing factor system in rats.
AB  - Although orexin-A peptide was recently found to inhibit the brain reward system,
      the exact neural substrates for this phenomenon remain unclear. The aim of the
      present study was to investigate the role of orexin neurons in intra-cranial self
      stimulation behavior and to clarify the pathways through which orexin-A inhibits
      the brain reward system. Immunohistochemical examination using Fos, a neuronal
      activation marker, revealed that the percentage of activated orexin cells was
      very low in the lateral hypothalamus even in the hemisphere ipsilateral to self
      stimulation, suggesting that orexin neurons play only a small part, if any, in
      performing intra-cranial self-stimulation behavior. Intra-ventral tegmental area
      administration of orexin-A (1.0 nmol) significantly increased the intra-cranial
      self-stimulation threshold. Furthermore, the threshold-increasing effects of
      intra-ventral tegmental area or intracerebroventricular orexin-A were inhibited
      by administration of the nonspecific corticotropin-releasing factor receptor
      antagonist, d-Phe-CRF(12-41) (20 MUg). Following intra-ventral tegmental area
      infusion of orexin-A, the percentage of cells double-labeled with corticotropin
      releasing factor and Fos antibodies increased in the central nucleus of the
      amygdala but not in the bed nucleus of the stria terminalis, and brain
      microdialysis analyses indicated that dopamine efflux in both the central nucleus
      of the amygdala and bed nucleus of the stria terminalis were enhanced. Taken
      together, the present findings suggest that intra-ventral tegmental area or
      intracerebroventricular administration of orexin-A exerts its threshold
      increasing effect via subsequent activation of the corticotropin-releasing factor
      system.

PMID- 21848923
TI  - Long-term exposure to music enhances the sensitivity of the auditory system in
      children.
AB  - This event-related brain potential study aims to contribute to the present debate
      regarding the effect of musical training on the maturation of the human auditory
      nervous system. To address this issue, we recorded the mismatch negativity (MMN)
      evoked by violin and pure sine-wave tones in a group of 7.5- to 12-year-old
      children who had either several years of musical experience with Suzuki violin
      lessons, or no musical training. The strength of the MMN responses to violin
      tones evident in the Suzuki students clearly surpassed responses in controls; the
      reverse pattern was observed for sine-wave tones. Suzuki students showed
      significantly shorter MMN latencies to violin tones than to pure tones; the MMN
      latency did not differ significantly between pure tones and violin sounds in the
      control group. Thus, our data provide general evidence of how and to what extent
      extensive musical experience affects the maturation of human auditory function at
      multiple levels, namely, accuracy and speed of auditory discrimination
      processing. Our findings add to the present understanding of neuroplastic
      organization and function of the mammalian nervous system. Furthermore,
      behavioural recordings obtained from the participating children provide
      corroborating evidence for a relationship between the duration and intensity of
      training, the specific sensitivity to instrumental timbre, and pitch recognition
      abilities.

PMID- 21848922
TI  - Modulation by the BK accessory beta4 subunit of phosphorylation-dependent changes
      in excitability of dentate gyrus granule neurons.
AB  - Large-conductance voltage- and calcium-activated potassium (BK) channels are
      large-conductance calcium- and voltage-activated potassium channels critical for
      neuronal excitability. Some neurons express so called fast-gated, type I BK
      channels. Other neurons express BK channels assembled with the accessory beta4
      subunit conferring slow gating of type II BK channels. However, it is not clear
      how protein phosphorylation modulates these two distinct BK channel types. Using
      beta4-knockout mice, we compared fast- or slow-gated BK channels in response to
      changes in phosphorylation status of hippocampus dentate gyrus granule neurons.
      We utilized the selective PP2A/PP4 phosphatase inhibitor Fostriecin to study
      changes in action potential shape and firing properties of the neurons. In beta4
      knockout neurons, Fostriecin increases BK current, speeds up BK channel
      activation and reduces action potential amplitudes. Fostriecin increases spiking
      during early components of an action potential train. In contrast, inhibition of
      BK channels through beta4 in wild-type neurons or by the BK channel inhibitor
      Paxilline opposes Fostriecin effects. Voltage clamp recordings of neurons reveal
      that Fostriecin increases both calcium and BK currents. However, Fostriecin does
      not activate BK alpha channels in transfected HEK293 cells lacking calcium
      channels. In summary, these results suggest that fast-gating, type I BK channels
      lacking beta4 can increase neuronal excitability in response to reduced
      phosphatase activity and activation of calcium channels. By opposing BK channel
      activation, the beta4 subunit plays an important role in moderating firing
      frequency regardless of changes in phosphorylation status.

PMID- 21848924
TI  - The neural network of phantom sound changes over time: a comparison between
      recent-onset and chronic tinnitus patients.
AB  - Tinnitus is characterized by an ongoing conscious perception of a sound in the
      absence of any external sound source. Chronic tinnitus is notoriously
      characterized by its resistance to treatment. In the present study the objective
      was to verify whether the neural generators and/or the neural tinnitus network,
      evaluated through EEG recordings, change over time as previously suggested by
      MEG. We therefore analyzed the source-localized EEG recordings of a very
      homogenous group of left-sided narrow-band noise tinnitus patients. Results
      indicate that the generators involved in tinnitus of recent onset seem to change
      over time with increased activity in several brain areas [auditory cortex,
      supplementary motor area and dorsal anterior cingulate cortex (dACC) plus
      insula], associated with a decrease in connectivity between the different
      auditory and nonauditory brain structures. An exception to this general
      connectivity decrease is an increase in gamma-band connectivity between the left
      primary and secondary auditory cortex and the left insula, and also between the
      auditory cortices and the right dorsal lateral prefrontal cortex. These networks
      are both connected to the left parahippocampal area. Thus acute and chronic
      tinnitus are related to differential activity and connectivity in a network
      comprising the auditory cortices, insula, dACC and premotor cortex.

PMID- 21848925
TI  - The effectiveness of Internet-based blood glucose monitoring system on improving
      diabetes control in adolescents with type 1 diabetes.
AB  - OBJECTIVE: To determine whether the use of an Internet-based blood glucose
      monitoring system could improve glycemic control in adolescents with type 1
      diabetes mellitus (T1DM). METHODS: In a randomized, controlled clinical trial, a
      total of 70 adolescent subjects with T1DM were recruited. Subjects randomized to
      the intervention group (n = 36) were instructed to submit their blood glucose
      levels weekly by Internet to the diabetes care team during a period of 6 months.
      Subjects randomized to the control group (n = 34) did not submit results but were
      under routine follow-up. RESULTS: At baseline, patients were 15.1 +/- 2.6 years
      of age with mean HbA1c of 8.3 +/- 1.3%. At the 6-month follow-up period, no by
      group differences in change from baseline to end of treatment HbA1c levels were
      detected. In the intervention group, 12/36 did not submit blood glucose levels
      and were classified as non-compliant. In a secondary exploratory analysis in
      which non-compliant patients were omitted, HbA1c values in the compliant
      intervention group declined from 8.5 +/- 1.7% at baseline to 8.2 +/- 1.2% at 6
      months, while in the control group HbA1c values increased from 8.2 +/- 1.1 to 8.4
      +/- 1.1%, this difference did not reach statistical significance. CONCLUSIONS: An
      Internet-based blood glucose monitoring system was not associated with improved
      glycemic control in adolescents with T1DM. Identification of a sub-group of
      compliant subjects who may improve metabolic control by using this tool is
      needed.

PMID- 21848926
TI  - Leading change: a three-dimensional model of nurse leaders' main tasks and roles
      during a change process.
AB  - AIM: This paper is a report of a qualitative study which explored how nurse
      leaders described and understood their main tasks and roles during a change
      process. BACKGROUND: During a database search for literature, no actual research
      that highlighted the main tasks and roles of nurse leaders during a change
      process was found. Earlier research has indicated the need for different
      leadership styles and the importance of strategies and values. METHOD: In-depth
      interviews with 17 nurse leaders took place in 2004. A phenomenological
      hermeneutical approach was used for data analysis. RESULTS: The findings resulted
      in a model of leading change in health care that focuses on good patient care and
      consists of three dimensions: leading relationships, leading processes and
      leading a culture. In addition to leading relationships and processes, nurse
      leaders, as role models, greatly impact caring culture and its inherent ethical
      behaviour, especially about the responsibility for achieving good patient care.
      Nurse leaders are also instrumental in leading ward culture. CONCLUSION: Nurse
      leaders need guidance and knowledge of what is expected of them during a
      structural change process. They play different roles by directing, guiding,
      motivating, supporting and communicating without losing their cultural ethos of
      caring and use various leadership styles to bring about actual change, which, in
      turn, requires learning so that the thought patterns, values and attitudes of
      personnel can be changed.

PMID- 21848927
TI  - GAD autoantibody epitope pattern after GAD-alum treatment in children and
      adolescents with type 1 diabetes.
AB  - AIMS: We have previously shown that two injections of glutamic acid decarboxylase
      formulated in alum (GAD-alum) preserved residual insulin secretion in children
      and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by
      increased GAD autoantibody (GADA) titers. The aim of this study was to
      investigate whether GAD-alum treatment affected the GADA epitope pattern.
      METHODS: Serum samples from patients treated with GAD-alum (n = 33) or placebo (n
      = 27), at baseline, 1, 3, 9, and 15 months after the initial injection, were
      tested for their binding capacity to specific GADA epitopes in an epitope
      specific radioligand binding assay with six recombinant Fab (rFab) (b96.11, DPA,
      DPD, MICA3, b78, and N-GAD(65) mAb). RESULTS: No significant differences in
      variability of binding to any of the tested rFab were observed from baseline to
      15 months. There was a sustained low binding of GADA to the b78- and N-GAD(65)
      mAb-defined epitopes, often recognized by GADA in patients with stiff person
      syndrome (SPS) and seldom in T1D patients. However, binding of GADA to the T1D
      associated b96.11-defined epitope increased between baseline and 3 months in GAD
      alum (-8.1%, min -72.4%, max 39.6%) compared to placebo patients (1.5%, min 
      28.3%, max 28.6%) (p = 0.02). Subsequently, the b96.11-defined epitope
      recognition returned to levels similar to that observed at baseline. CONCLUSIONS:
      GAD-alum injections did not affect binding of GADA to SPS-related epitopes,
      further supporting the safety of the treatment. There were no changes in GADA
      epitope specificity to the T1D-related epitopes, except for a temporarily
      increased binding to one of the tested epitopes.

PMID- 21848928
TI  - The endothelium modulates the arterial wall mechanical response to intra-aortic
      balloon counterpulsation: in vivo studies.
AB  - Intra-aortic balloon pump (IABP) benefits could depend on variations in the
      cardiovascular biomechanical properties associated with blood flow-induced
      endothelium-dependent changes. However, if IABP results in changes in the
      peripheral artery biomechanics and if the endothelium plays a role in these
      potential changes remains unknown. The aim of this study is to characterize acute
      IABP effects on peripheral artery biomechanics in control and acute heart failure
      (AHF) states and the role of the endothelium in IABP effects on peripheral artery
      biomechanics. Pressure and diameter were recorded in sheep (n= 7) iliac arteries
      (IAs), before and during 1:2 IABP, during four states: (i) control with intact
      IA; (ii) AHF with intact IA; (iii) control with de-endothelialized (DE)
      (mechanical rubbing) IA; and (iv) AHF with DE IA. Arterial distensibility,
      elastic modulus, and conduit function (CF) (1/characteristic impedance) were
      calculated. The results of this study include: (i) during control conditions,
      IABP resulted in intact IA dilatation, stiffness reduction, and CF increase; (ii)
      AHF induction determined a reduction in intact IA diameter and CF, and a
      stiffness increase. These changes reverted during IABP; (iii) the increase in IA
      stiffness observed after DE remained unchanged during IABP; (iv) in DE IA, AHF
      did not result in diameter or stiffness changes; and (v) IABP during AHF did not
      associate changes in diameter or stiffness in the DE IA. In conclusion, during
      control and AHF states, IABP results in IA dilatation and stiffness reduction.
      The integrity of the endothelial layer would be critical for the IABP-associated
      changes in IA biomechanics.

PMID- 21848929
TI  - Intra-dialytic electrostimulation of leg extensors may improve exercise tolerance
      and quality of life in hemodialyzed patients.
AB  - Hemodialyzed (HD) patients with end-stage renal disease (ESRD) exhibit lower
      fitness as a consequence of chronic uremic changes that trigger various
      structural, metabolic, and functional abnormalities in skeletal muscles. The aim
      of this randomized study was to compare the effect of rehabilitation (RHB)
      training on a bicycle ergometer and electromyostimulation (EMS) of leg extensors
      in HD patients with ESRD. Thirty-two HD patients (18 men/14 women; mean age 61.1
      +/- 8.8 years) were randomized into three groups: (i) exercise training (ET; n =
      11) on bicycle ergometer 2 * 20 min; (ii) EMS (n = 11) where stimulation (10 Hz)
      of leg extensors was applied for 60 min; and (iii) controls (CON; n = 10) without
      exercise. Exercising was performed between the 2nd and the 3rd hour of HD, three
      times a week, 20 weeks in total. Ergometric test was performed in order to
      evaluate peak workload (W(peak)), 6-min corridor walking test (CWT) to evaluate
      the distance walked, and dynamometry of leg extensors to assess muscle power
      (F(max)). Urea clearance was monitored and expressed as standard parameters:
      spKt/V, spKt/V equilibrated (spKt/V-e), and the urea removal ratio (URR). Quality
      of life (QoL) was assessed by the questionnaire SF-36. A significant increase of
      F(max) (P = 0.040 in group ET; P = 0.032 in group EMS), of 6-min CWT (P < 0.001
      in ET group; P = 0.042 in EMS group), and of W(peak) (P = 0.041 in ET group) was
      observed. In both exercising groups, significant increase of spKt/V, spKt/V-e,
      and URR was found as compared with initial values (P < 0.05). In both exercising
      groups, highly significant changes in summarized mental functions were found (P =
      0.001); in summarized physical components, significant improvement was observed
      in the ET group (P = 0.006). Intradialytic RHB showed comparable positive effects
      on functional parameters, urea clearance, and QoL. Intradialytic EMS might
      represent wide therapeutic possibility in the near future.

PMID- 21848930
TI  - Impact of hemoglobin concentration and affinity for oxygen on tissue oxygenation:
      the case of hemoglobin-based oxygen carriers.
AB  - In patients undergoing exchange-transfusion with hemoglobin (Hb)-based oxygen
      (O2) carriers (HBOC), native Hb coexists with newly transfused Hb. The two Hb
      types share the same arterial and venous PO2, but their affinities for O2 vary. A
      simple spreadsheet model is described aiming at evaluating the contribution of
      each Hb type to the overall O2 transport characteristics as a function of the
      batch Hb concentration and O2 affinity in the HBOC solution, of the fraction of
      exchange-transfused blood/HBOC, and of the arterial PO2. This model helps to
      yield a quantitative estimate of how tissues with high or low O2 extraction
      respond to the changes cited above. The results show that the higher the exchange
      transfusion ratio, the O2 transport to tissues becomes progressively impaired.
      However, this effect is more critical at low batch Hb concentration and high O2
      affinity of the HBOC, especially for tissues/organs with high O2 extraction,
      whereas the arterial PO2 does not appear as critical.

PMID- 21848932
TI  - Sarcocystis calchasi-associated neurologic disease in a domestic pigeon in North
      America.
AB  - Tissue cysts of a protozoan parasite were present in the skeletal muscle of a
      domestic pigeon (Columba livia f. domestica) with neurologic disease in
      Minnesota, USA. The animal had a severe granulomatous meningoencephalitis. The
      cysts were slender, up to 1 mm long and up to 0.03 mm in diameter. The cysts had
      a smooth wall without projections. Size and wall morphology were compatible with
      Sarcocystis calchasi. Polymerase chain reaction using S. calchasi-specific
      primers resulted in a specific amplicon from the skeletal muscle but not from the
      brain. Sequencing of the highly variable genomic regions ITS1 and D2 revealed
      100% nucleic acid identity with the German strain of S. calchasi. Sarcocystis
      calchasi is the cause of an emerging lethal disease in pigeons in Germany. This
      is the first description of the parasite outside of Germany.

PMID- 21848931
TI  - Pharmacodynamic and pharmacokinetic basics of rivaroxaban.
AB  - Rivaroxaban, an oral, direct factor Xa inhibitor, is a small molecule drug
      capable of inhibiting not only free factor Xa with high selectivity but also
      prothrombinase-bound and clot-associated factor Xa in a concentration-dependent
      manner. Clinical studies have demonstrated predictable anticoagulation and
      confirmed dose-proportional effects for rivaroxaban in humans with a rapid onset
      (within 2-4 h) and a half-life of 7-11 h and 11-13 h for young and elderly
      subjects, respectively. For a 10 mg dose, the oral bioavailability of rivaroxaban
      is high (80-100%) and is not affected by food intake. These favourable
      pharmacological properties underpin the use of rivaroxaban in fixed dosing
      regimens, with no need for dose adjustment or routine coagulation monitoring.
      Rivaroxaban has a dual mode of excretion with the renal route accounting for one
      third of the overall elimination of unchanged active drug. Rivaroxaban is a
      substrate of CYP3A4 and P-glycoprotein and therefore not recommended for
      concomitant use with strong inhibitors of both pathways, e.g. most azole
      antimycotics and protease inhibitors. Rivaroxaban is currently approved for the
      prevention of venous thromboembolism (VTE) in adult patients undergoing elective
      hip or knee replacement surgery. Studies using 10 mg rivaroxaban once daily in
      this indication demonstrated its suitability for a wide range of patients
      regardless of age, gender or body weight. Further studies in the treatment of
      VTE, prevention of cardiovascular events in patients with acute coronary
      syndrome, prevention of stroke in those with atrial fibrillation and prevention
      of VTE in hospitalized medically ill patients have been reported or are ongoing.

PMID- 21848933
TI  - Coronary vascular resistance increases under full bypass support of centrifugal
      pumps--relation between myocardial perfusion and ventricular workload during pump
      support.
AB  - Coronary circulation is closely linked to myocardial oxygen consumption (MVO(2)),
      and previous reports have suggested decreased coronary flow (CoF) under left
      ventricular assist device support. Decreased CoF itself under support is not
      unfavorable because the native heart can be well unloaded and myocardial oxygen
      demand is also decreased. There should be an autoregulatory system that would
      maintain optimal CoF according to oxygen demand; however, the detailed mechanism
      is still unclear. The aim of the current study is to evaluate the effect of
      centrifugal pumps on CoF under varied bypass rates in relation to left ventricle
      workload. A centrifugal pump, EVAHEART (Sun Medical Technology Research
      Corporation, Nagano, Japan), was installed in an adult goat (n = 10, 61.3 +/- 6.5
      kg). We set up the following conditions, including Circuit-Clamp (i.e., no pump
      support), 50% bypass, and 100% bypass. In these settings, CoF, MVO(2), pressure
      volume area (PVA), and coronary vascular resistance (CVR) were measured. In 100%
      bypass, CoF, MVO(2), and PVA were all decreased significantly from clamp. While
      in 50% bypass, CoF and MVO(2) decreased from clamp, but not PVA. There was a
      significant 40% increase in CVR in 100% bypass from clamp. This CVR increase in
      100% bypass was possibly due to mechanical collapse of coronary vascular bed
      itself by pump support or increased vascular tone through autoregulatory system.
      In clinical settings, we should adjust optimal pump speed so as not to cause this
      vascular collapse. However, to clarify autoregulatory system of the coronary
      perfusion, further investigation is ongoing in ischemic and heart failure models.

PMID- 21848934
TI  - Differential expression of proinflammatory cytokines in the lymphoid organs of
      porcine reproductive and respiratory syndrome virus-infected pigs.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is considered one of the
      most important diseases in the swine industry. Although several studies have been
      carried out to elucidate the host immune response evoked against PRRS virus
      (PRRSV), there are several aspects that still remain unclear. The aim of this
      study was to determine the expression of IL-1alpha, IL-6 and TNF-alpha in the
      lymphoid organs (mediastinal and retropharyngeal lymph nodes and tonsil) of PRRSV
      infected pigs and to determine their correlation with the expression of PRRSV
      antigen. Proinflammatory cytokine expression was different depending on the body
      compartment examined. Thus, whereas IL-1alpha and TNF-alpha were the main
      cytokines expressed in the mediastinal lymph node, IL-6 was the most highly
      expressed cytokine in the retropharyngeal lymph node, and no expression of
      proinflammatory cytokines was observed in the tonsil. These findings may be
      related to the impairment of the host immune response evoked after PRRSV
      infection. Therefore, lymphoid organs and proinflammatory cytokines represent an
      important target of study for clarifying the immunopathogenesis of PRRS.

PMID- 21848935
TI  - Electrospun small-diameter polyurethane vascular grafts: ingrowth and
      differentiation of vascular-specific host cells.
AB  - No small-diameter synthetic graft has yet shown comparable performance to
      autologous vessels. Synthetic conduits fail due to their inherent surface
      thrombogenicity and the development of intimal hyperplasia. In addressing these
      shortcomings, electrospinning offers an interesting alternative to other
      nanostructured, cardiovascular substitutes because of the close match of
      electrospun materials to the biomechanical and structural properties of native
      vessels. In this study, we investigated the in vivo behavior of electrospun,
      small-diameter conduits in a rat model. Vascular grafts composed of polyurethane
      were fabricated by electrospinning. Prostheses were implanted into the abdominal
      aorta in 40 rats for either 7 days, 4 weeks, 3 months, or 6 months. Retrieved
      specimens were evaluated by histology, immunohistochemical staining, confocal
      laser scanning microscopy, and scanning electron microscopy. At all time points,
      we found no evidence of foreign body reaction or graft degradation. The overall
      patency rate of the intravascular implants was 95%. Within 7 days, grafts
      revealed ingrowth of host cells. CD34+ cells increased significantly from 7 days
      up to 6 months of implantation (P < 0.05). Myofibroblasts and myocytes showed
      increasing cell numbers up to 3 months (P < 0.05). Ki67 staining indicated
      unaltered cell proliferation during the whole follow-up period. Besides
      biomechanical benefits, electrospun polyurethane grafts exhibit excellent
      biocompatibility in vivo. Cell immigration and differentiation seems to be
      promoted by the nanostructured artificial matrix.

PMID- 21848936
TI  - Osmolal gap in hemodialyzed uremic patients.
AB  - Osmolality is an expression of the number of particles in a given weight of
      solvent (mOsm). Measured osmolality is determined by the osmometer, and
      calculated osmolality is estimated by 2xNa + UN/2.8 + glucose/18. The difference
      between measured and calculated osmolality is the osmolal gap. The purpose of the
      present study is to determine the measured and the calculated osmolality and the
      osmolal gap in hemodialyzed uremic patients, pre- and post-hemodialysis (HD). In
      24 uremic patients under regular HD, blood samples pre- and post-HD were
      collected, and serum osmolality measured (osmometer) and calculated (2xNa +
      UN/2.8 + glucose/18) and the osmolal gap (measured-calculated osmolality) were
      determined. Also, the same parameters were determined in 22 healthy subjects
      (control). According to our findings, the measured osmolality in patients is
      significantly higher pre- and post-HD in comparison to that of controls, but post
      HD is significantly lower than pre-HD. Also, calculated osmolality is
      significantly higher pre- and post-HD in comparison to that of controls, but the
      value post-HD is significantly lower than the pre-HD. The osmolal gap of patients
      pre-HD (11 +/- 2.08) and post-HD (7.29 +/- 1.94) is significantly higher (P <
      0.001) in comparison to that of controls (3.18 +/- 1.46); also, the value post-HD
      is significantly decreased in comparison to the value pre-HD (P < 0.001). Uremic
      hemodialyzed patients present high measured and calculated osmolality pre-HD that
      remains high post-HD in comparison to that of controls in spite of the
      significant decrease post-HD in comparison to that of pre-HD. Also, the osmolal
      gap is high pre-HD and, in spite of the decrease, remains high post-HD. In
      comparison to that of controls, the high osmolal gap indirectly indicates the
      presence of unidentified endogenous osmoles in the serum of uremic patients which
      partly are removed during HD.

PMID- 21848937
TI  - Determining factors in evidence-based clinical practice among hospital and
      primary care nursing staff.
AB  - AIM: The general aim of this study is to identify key factors perceived by nurses
      to influence evidence-based clinical practice at different centres. BACKGROUND:
      During the last decade, there has been an increased interest in the
      identification of factors that facilitate the transfer of knowledge into clinical
      practice, among health care professionals. Previous research states that a
      suitable organisational framework and practice environment seems to have
      influence on a greater use of scientific evidence by nurses, which can be
      directly observed in patient outcomes. In consequence, several authors suggest
      that strategies should be encouraged from managers and nurse executives to
      guarantee the existence of environments that avoid emotional exhaustion and
      improve satisfaction of nurses with their work, and at the same time, ensure the
      use of research-guided nursing decisions. METHODS: Following the Spanish
      validation of the Practice Environment Scale-Nursing Work Index and Evidence
      Based Practice Questionnaire, a descriptive observational cross-sectional study
      has been conceived, from 2010 to 2011, in order to identify determining factors
      in evidence-based clinical practice at different centres. In a second phase, a
      qualitative study has been designed, using focus groups, to identify practice
      factors that can lead to a successful implementation of evidence-based clinical
      practice. DISCUSSION: Organisational and attitudinal interventions are needed in
      order to implement evidence-based clinical practice that improves the quality of
      patient care.

PMID- 21848938
TI  - 'Providing more scaffolding': parenting a child with developmental co-ordination
      disorder, a hidden disability.
AB  - BACKGROUND: Few studies exist reporting the experiences of parents of children
      with developmental co-ordination disorder (DCD) a common disorder with a
      prevalence of 1.8-6%. DCD is characterized by poor motor co-ordination, not
      caused by a general medical condition, but significantly affecting daily living.
      This study explores the experiences of parents living with a child with DCD in
      obtaining a diagnosis; the impact of the diagnosis on parenting and the effect on
      parents as individuals. METHODS: Semi-structured interviews with a purposive
      sample of 15 parents of children with DCD data were recorded and then
      transcribed. Data were analysed using a coding framework and themes identified
      similar to Attride-Stirling (2001, Qualitative Research, 1, 385-405). FINDINGS:
      DCD was an all-encompassing condition that dominated all aspects of family life
      and was a 'hidden disability'. Parents were frustrated by the poor knowledge and
      expertise of health and education professionals working with children with DCD
      and the lack of good quality accessible information and support services. Parents
      became by default the 'expert' on DCD for schools and other services; they were
      advocates for DCD and their own children. They provided additional support for
      longer to their child with DCD and had concerns for their future. Parenting a
      child with DCD was frustrating, exhausting, guilt-ridden as well as rewarding.
      There was little available time to provide for the needs of other family members.
      CONCLUSION: A better-trained, knowledgeable workforce would redress the balance
      for families with DCD by providing better information, support and advocacy
      freeing parents to parent their families.

PMID- 21848939
TI  - The virtue of uncertainty in health care.
AB  - Uncertainty is unavoidable in health care, yet frequently tacit. When uncertainty
      is acknowledged, it tends to be defined in terms of the unpredictable nature of
      the care, and limits to human knowledge. It is cast as a problem that evidence
      based health care can minimize. Challenging that simplistic perspective, this
      paper reconstructs uncertainty as a property whose meaning derives from how
      people are relationally disposed to perceive it in the social context in which
      they are embedded. Five conditions are suggested to define a need to protect and
      cultivate uncertainty as a virtue or positive disposition. These conditions are
      that uncertainty is natural, promotes creativity and a critical attitude, can
      signify wisdom, nurtures safety, sustains hope and protects against excess. In
      contrast, certainty is a delusion. Believing in certainty is unscientific and
      antiscientific because it can obscure and devalue critique in scientific
      practice.

PMID- 21848940
TI  - Researching involvement in health care practices: interrupting or reproducing
      medicalization?
AB  - In this paper we reflect upon and problematize the ways in which 'patient
      involvement' is interpreted in a substantial proportion of the research
      literature on involvement and shared decision making. Drawing upon an analysis of
      this literature we raise concerns about the 'medicalization of involvement'
      embedded in, and reproduced by, some dominant research lenses, suggesting that
      this medicalization has powerful discursive and material effects. For example, we
      suggest that it tends to normalize and arguably trivialize intrinsically
      problematic and contentious concepts such as 'patient preferences' and, at the
      same time, to obscure the full range of possibilities for reciprocity in the
      exchanges between the medical world of the professional and the experiential and
      narrative world of the patient. We argue that richer conceptualizations of
      collaboration in clinical work are both possible and very much needed, and we
      indicate some examples of scholarly resources and perspectives that point towards
      richer and more defensible accounts of involvement. Overall we call for more
      attention to the idea of 'epistemic involvement' and much greater cross
      fertilization between different epistemological paradigms in this area of
      research.

PMID- 21848941
TI  - Evidence-based medicine and progress in the medical sciences.
AB  - The question what scientific progress means for a particular domain such as
      medicine seems importantly different from the question what scientific progress
      is in general. While the latter question received ample treatment in the
      philosophical literature, the former question is hardly discussed. I argue that
      it is nonetheless important to think about this question in view of the
      methodological choices we make. I raise specific questions that should be tackled
      regarding scientific progress in the medical sciences and demonstrate their
      importance by means of an analysis of what evidence-based medicine (EBM) has, and
      has not, to offer in terms of progress. I show how critically thinking about EBM
      from the point of view of progress can help us in putting EBM and its favoured
      methodologies in the right perspective. My conclusion will be that blindly
      favouring certain methods because of their immediately tangible short-term
      benefits implies that we parry the important question of how best to advance
      progress in the long run. This leads us to losing sight of our general goals in
      doing research in the medical sciences.

PMID- 21848942
TI  - Detecting deterioration in patients with chronic disease using telemonitoring:
      navigating the 'trough of disillusionment'.
AB  - OBJECTIVES: To examine the evidence base for telemonitoring designed for patients
      who have chronic obstructive pulmonary disease and heart failure, and to assess
      whether telemonitoring fulfils the principles of monitoring and is ready for
      implementation into routine settings. DESIGN: Qualitative data collection using
      interviews and participation in a multi-path mapping process. PARTICIPANTS:
      Twenty-six purposively selected informants completed semi-structured interviews
      and 24 individuals with expertise in the relevant clinical and informatics
      domains from academia, industry, policy and provider organizations and
      participated in a multi-path mapping workshop. RESULTS: The evidence base for the
      effectiveness of telemonitoring is weak and inconsistent, with insufficient cost
      effectiveness studies. When considered against an accepted definition of
      monitoring, telemonitoring is found wanting. Telemonitoring has not been able so
      far to ensure that the technologies fit into the life world of the patient and
      into the clinical and organizational milieu of health service delivery systems.
      CONCLUSIONS: To develop effective telemonitoring for patients with chronic
      disease, more attention needs to be given to agreeing the central aim of early
      detection and, to ensure potential implementation, engaging a wide range of
      stakeholders in the design process, especially patients and clinicians.

PMID- 21848943
TI  - How avian nest site selection responds to predation risk: testing an 'adaptive
      peak hypothesis'.
AB  - 1. Nest predation limits avian fitness, so birds should favour nest sites that
      minimize predation risk. Nevertheless, preferred nest microhabitat features are
      often uncorrelated with apparent variation in predation rates. 2. This lack of
      congruence between theory-based expectation and empirical data may arise when
      birds already occupy 'adaptive peaks'. If birds nest exclusively in low-predation
      microhabitats, microhabitat and nest predation may no longer be correlated even
      though predation ultimately shaped microhabitat selection. 3. This 'adaptive peak
      hypothesis' was tested for a population of Yellow Warblers (Dendroica petechia)
      focusing on two nest microhabitat features: concealment and height. Experimental
      nests measured relative predation risk both within and outside the microhabitat
      range typically occupied by natural nests to examine whether nest site choices
      made by birds restricted our ability to detect microhabitat effects on predation.
      4. Within the natural range (30-80% concealment, >75 cm height), microhabitat
      predation relationships were weak and inconsistent, and similar for experimental
      and natural nests. Over an extended range, however, experimental predation rates
      were elevated in exposed sites (<30% concealed), indicating a concealment-related
      'adaptive plateau'. 5. Clay egg bite data revealed a concealment effect on avian
      predators, and the abundance of one avian predator group correlated with nest
      concealment among years, suggesting these predators may cue birds to modulate
      nest concealment choices. 6. This study demonstrates how avian responses to
      predation pressure can obscure the adaptive significance of nest site selection,
      so predation influences may be more important than apparent from published data.

PMID- 21848944
TI  - Effect of tibial tuberosity advancement on the contact mechanics and the
      alignment of the patellofemoral and femorotibial joints.
AB  - OBJECTIVE: To evaluate the effect of tibial tuberosity advancement (TTA) on
      patellofemoral (PF) contact mechanics, and alignment of the PF and femorotibial
      (FT) joints in cranial cruciate ligament (CrCL)-deficient stifles of dogs. STUDY
      DESIGN: Ex vivo biomechanical study. ANIMALS: Unpaired cadaveric hind limbs
      (n=9). METHODS: Digital pressure sensors placed in the PF joint were used to
      measure contact force, contact area, peak and mean contact pressure, and peak
      pressure location with the limb under an axial load of 30% body weight and a
      stifle angle of 135 degrees . The FT and PF poses were obtained using a 2
      dimensional computer digitization technique. Each specimen was tested under
      normal, CrCL-deficient, and TTA-treated conditions. Data was normalized and
      analyzed, after testing for normality by Wilk-Shapiro, using 1 sample T-test,
      paired T-test, and ANOVA; P<=.05 was considered significant. Bonferroni's
      correction was used when needed. RESULTS: A significant cranioproximal tibial
      displacement and increase in patellar tilt were found in the CrCL-deficient
      joints. Both FT and PF alignments were restored after TTA. Contact areas and peak
      pressure did not vary between conditions. Peak pressure location displaced
      proximally from intact to CrCL-deficient condition and returned to normal after
      TTA. Total force measured in the CrCL-deficient stifle and TTA conditions were
      significantly lower than in the control. CONCLUSION: TTA restored the normal FT
      and PF alignment, and reduced the retropatellar force by about 20%.

PMID- 21848945
TI  - Absence of equid herpesvirus-1 reactivation and viremia in hospitalized
      critically ill horses.
AB  - BACKGROUND: Equid herpesvirus-1 (EHV-1) reactivation and shedding can occur in
      latently infected, asymptomatic animals. Risk factors for reactivation include
      stress and illness. The risk of asymptomatic shedding in hospitalized, critically
      ill horses with acute abdominal disease is unknown. This information is important
      to assess the need for additional biosecurity protocols to prevent spread of EHV
      1 in hospitalized critically ill horses with acute abdominal disorders.
      OBJECTIVES: To determine the frequency of reactivation and nasal shedding of EHV
      1 in hospitalized critically ill horses. ANIMALS: One hundred twenty-four client
      owned horses admitted to the Veterinary Teaching Hospital with acute abdominal
      disorders were included in the study. METHODS: Cross-sectional study examining
      the risk of reactivation of EHV-1 in horses admitted with acute, severe,
      gastrointestinal disease. Whole blood and nasal secretions were collected
      throughout hospitalization. In addition, mandibular lymph nodes were collected
      from 9 study horses and 26 other Michigan horses. All samples were tested for the
      presence of EHV-1 nucleic acid by real-time PCR assays targeting the glycoprotein
      B gene and the polymerase (ORF 30) gene. RESULTS: One hundred and twenty-four
      horses met the inclusion criteria. None of the samples were positive for EHV-1
      DNA. CONCLUSION AND CLINICAL IMPORTANCE: These results suggest that nasal
      shedding and viremia of EHV-1 in hospitalized critically ill horses with acute
      abdominal disorder is extremely rare. Implementation of additional biosecurity
      protocols to limit aerosol spread of EHV-1 among horses with acute abdominal
      disease and other hospitalized horses is not necessary.

PMID- 21848946
TI  - Assessment of global and regional left ventricular volume and shape by real-time
      3-dimensional echocardiography in dogs with myxomatous mitral valve disease.
AB  - BACKGROUND: Left ventricular (LV) remodeling occurs in response to chronic volume
      overload. Real-time 3-dimensional (RT3D) echocardiography offers new modalities
      for LV assessment. OBJECTIVE: To investigate LV changes in shape and volume in
      response to different severities of naturally acquired myxomatous mitral valve
      disease (MMVD) in dogs by RT3D echocardiography. ANIMALS: Sixty-five client-owned
      dogs. METHODS: Prospectively recruited dogs were classified by standard
      echocardiography into healthy, mild, moderate, and severe MMVD groups.
      Endocardial border tracking of LV RT3D dataset was performed, from which global
      and regional (automatically acquired basal, mid, and apical segments based on LV
      long-axis length) end-diastolic (EDV) and end-systolic volumes (ESV), LV long
      axis length, and sphericity index were obtained. RESULTS: Global and regional EDV
      and ESV (indexed to body weight) were most prominently increased in dogs with
      severe MMVD. All 3 regional LV segments contributed to increased global EDV and
      ESV with increasing MMVD severity, but mid-EDV contributed the most to the global
      EDV increase. Furthermore, LV long-axis length and LV sphericity index increased
      with increasing MMVD severity. Basal and apical EDV segments displayed the
      strongest association with sphericity index (P < .0001). CONCLUSIONS AND CLINICAL
      IMPORTANCE: The most prominent LV volume expansion was found in dogs with severe
      MMVD. Increased EDV, primarily in the mid-segment, leads to rounding of LV apical
      and basal segments in response to increasing MMVD severity. Assessment of LV
      volume and shape potentially could allow early detection of dogs at risk for
      rapid progression into congestive heart failure.

PMID- 21848947
TI  - Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal
      histomorphology, and urinary biomarkers.
AB  - BACKGROUND: Proteinuria is a feature of pyometra-associated renal dysfunction,
      but its prevalence and clinical relevance are not well characterized. OBJECTIVES:
      To define which subset of dogs with pyometra has clinically relevant kidney
      injury by quantification of proteinuria; light, immunofluorescence, and electron
      microscopic examination of kidney biopsy specimens; and measurement of urinary
      biomarkers. ANIMALS: Forty-seven dogs with pyometra. Ten clinically healthy
      intact bitches of comparable age. METHODS: Prospective study. Routine
      clinicopathological variables including urinary protein to creatinine ratio (UPC)
      were analyzed. Validated assays were used to quantify urinary biomarkers for
      glomerular (urinary albumin, urinary immunoglobulin G, urinary C-reactive
      protein, urinary thromboxane B(2)) and tubular function (urinary retinol-binding
      protein, urinary N-acetyl-beta-d-glucosaminidase). Kidney biopsy specimens from
      10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were
      collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after
      surgery in 9 of the 10 dogs. RESULTS: UPC (median, range) was significantly
      higher in dogs with pyometra (0.48, 0.05-8.69) compared with healthy bitches
      (0.08, 0.02-0.16) (P < .01). Twenty-two of 47 dogs with pyometra had UPC>0.5, 12
      had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial
      nephritis were common kidney biopsy findings in proteinuric dogs with pyometra.
      Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had
      UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and
      tubular changes mostly had urinary biomarker to creatinine ratios above the 75th
      percentile. CONCLUSION: Dogs with pyometra and UPC>1.0 or high ratios of urinary
      biomarkers appear likely to have clinically relevant renal histologic lesions and
      require monitoring after ovariohysterectomy. Future studies should evaluate the
      role of pyometra-associated pathogenic mechanisms in causing or exacerbating
      focal and segmental glomerulosclerosis in dogs.

PMID- 21848948
TI  - Prophylactic etoricoxib is effective in preventing "first of Ramadan" headache: a
      placebo-controlled double-blind and randomized trial of prophylactic etoricoxib
      for ritual fasting headache.
AB  - BACKGROUND: Religious fasting is associated with headache. This has been
      documented as "Yom Kippur headache" and "first of Ramadan headache." Etoricoxib,
      a Cox-2 inhibitor with a 22-hour half-life, has been shown effective in
      preventing fasting headache when taken just prior to the 25-hour Yom Kippur fast.
      We hypothesized that etoricoxib would also be effective in preventing headache
      during Ramadan, despite the different characteristics of the fast. METHODS: We
      performed a double-blind randomized prospective crossover trial of etoricoxib
      90mg vs placebo, taken just prior to the onset of fasting, during the first 2
      weeks of Ramadan 2010. Healthy adults aged 18-65 years were enrolled.
      Demographics, headache history and a daily post-fast survey were collected. We
      compared incidence, time of onset, and intensity of headache on each day and side
      effects in control and treatment groups. RESULTS: We enrolled 222 patients and
      189 completed the post-fast questionnaire (87%). Etoricoxib reduced the incidence
      of "first of Ramadan" headache by 54% (46% in placebo group [n=92] vs 21% [n=96]
      in etoricoxib group) (P<.0001, OR 3.19 [95% CI 1.68-6.06]). For days 1-6, the
      mean number of headache days for the placebo group was 1.60 (n=92) and for the
      treatment group the mean was 0.86 (n=99) headache days (P=.003). Median severity
      of headache in the treatment group was significantly lower. In the second week,
      there was no significant difference in incidence of headache between groups, and
      the incidence of headache in the placebo group dropped markedly over time.
      CONCLUSION: Etoricoxib 90mg taken prior to a 15-hour ritual fast decreases
      incidence of and attenuates headache during the first 5 days of the month of
      Ramadan.

PMID- 21848949
TI  - Headache in the emergency department.

PMID- 21848950
TI  - Alternative headache treatments: nutraceuticals, behavioral, and physical
      treatments.

PMID- 21848951
TI  - Transient global amnesia triggered by migraine in monozygotic twins.
AB  - Transitory global amnesia and migraine without aura are diseases with unclear
      pathophysiologic mechanisms, but with evidence of comorbidity. We describe twin
      monozygotic brothers, both presenting episodes of transitory global amnesia
      occurring only during attacks of migraine without aura. This report supports the
      hypothesis of a common underlying pathogenetic mechanism, possibly related to the
      cortical spreading depression. Furthermore, a common genetic trait in both the
      diseases or more probably in a particular subgroup of patients could be
      hypothesized.

PMID- 21848952
TI  - Headache induced by an ectopic tooth.

PMID- 21848953
TI  - Sustained effectiveness of occipital nerve stimulation in drug-resistant chronic
      cluster headache.
AB  - BACKGROUND: Drug-resistant chronic cluster headache (drCCH) is a devastating
      condition for which various invasive therapeutic procedures have been tempted
      without any satisfactory effect. Recent studies suggest that occipital nerve
      stimulation (ONS) could be an efficient preventive treatment of drCCH. OBJECTIVE:
      We conducted a prospective pilot trial of ONS in 8 subjects suffering from drCCH
      with encouraging results at 15 months. However, studies on a larger population
      with a longest follow-up were warranted. METHODS: We recruited 15 patients with
      drCCH according to the previously published criteria of intractability. They were
      implanted with suboccipital stimulators on the side of their headache. Long-term
      follow-up was achieved by questionnaires administered during a headache
      consultation and/or by phone interviews. RESULTS: Mean follow-up time post
      surgery is 36.82 months (range 11-64 months). One patient had an immediate post
      operative infection of the material. Among the 14 remaining patients, 11 (i.e.,
      ~80%) have at least a 90% improvement with 60% becoming pain-free for prolonged
      periods. Two patients did not respond or described mild improvement. Intensity of
      residual attacks is not modified by ONS. Four patients (29%) were able to reduce
      their prophylaxis. The major technical problems were battery depletion due to the
      use of high current intensities (N = 9/14, 64%) and immediate or delayed material
      infection (N = 3/15, 20%). Significant electrode migration was only seen in 1
      patient. Clinical peculiarities during the ONS follow-up period were side shift
      with infrequent contralateral attacks (N = 5/14, 36%), and/or isolated
      ipsilateral autonomic attacks without pain (N = 5/14, 36%). Two patients found
      ONS-related paresthesias unbearable: one had his stimulator removed, and the
      other switched it off although he was objectively ameliorated. Subjectively, 9
      patients are very satisfied by ONS and 3 patients moderately satisfied. Effective
      stimulation parameters varied between patients. CONCLUSIONS: Our long-term follow
      up confirms the efficacy of ONS in drCCH, which remains a safe and well-tolerated
      technique. The occurrence of contralateral attacks and isolated autonomic attacks
      in nearly 50% of ONS responders may have therapeutic and pathophysiological
      implications.

PMID- 21848954
TI  - African American and European American children in diverse elementary classrooms:
      social integration, social status, and social behavior.
AB  - With a sample of African American and European American 3rd- and 4th-grade
      children (N = 486, ages 8-11 years), this study examined classroom ethnic
      composition, peer social status (i.e., social preference and perceived popularity
      as nominated by same- and cross-ethnicity peers), and patterns of ethnic
      segregation (i.e., friendship, peer group, and cross-ethnicity dislike). African
      American--but not European American--children had more segregated relationships
      and were more disliked by cross-ethnicity peers when they had fewer same
      ethnicity classmates. African American children's segregation was positively
      associated with same-ethnicity social preference and perceived popularity and
      with cross-ethnicity perceived popularity. European American children's
      segregation was positively associated with same-ethnicity social preference but
      negatively associated with cross-ethnicity social preference and perceived
      popularity.

PMID- 21848955
TI  - The gap between Spanish speakers' word reading and word knowledge: a longitudinal
      study.
AB  - This longitudinal study modeled growth rates, from ages 4.5 to 11, in English and
      Spanish oral language and word reading skills among 173 Spanish-speaking children
      from low-income households. Individual growth modeling was employed using scores
      from standardized measures of word reading, expressive vocabulary, and verbal
      short-term language memory. The trajectories demonstrate that students' rates of
      growth and overall ability in word reading were on par with national norms. In
      contrast, students' oral language skills started out below national norms and
      their rates of growth, although surpassing the national rates, were not
      sufficient to reach age-appropriate levels. The results underscore the need for
      increased and sustained attention to promoting this population's language
      development.

PMID- 21848956
TI  - Update of prevalence of self-reported allergic rhinitis and chronic nasal
      symptoms among adults in Sweden.
AB  - BACKGROUND: Allergic rhinitis (AR) is the most common immunologic disease, and it
      renders a considerable burden on both sufferers and society. The prevalence of AR
      has been increasing worldwide over the past century. The aim of this study was to
      assess the present prevalence, risk factor patterns and comorbidity of self
      reported AR and chronic nasal symptoms in different age groups in Stockholm,
      Sweden. METHODS: A postal questionnaire was sent on two occasions, in 2006 to a
      population aged 30-80 years, randomly selected 10 years previously, and in 2007
      to a randomly selected sample of subjects aged 20-69 years. The response rates
      were 83% and 68%, respectively, and in total, 9792 subjects participated. The
      questionnaire included questions on self-reported AR, asthma, respiratory and
      nasal symptoms and possible determinants. RESULTS: The prevalence of self
      reported AR was 28.0% (men 26.6%, women 29.1%, P < 0.01) similar to 10 years
      previously and 33.6% in ages 30-40 years. Allergic heredity [odds ratio (OR)
      4.76, confidence interval (CI) 95% 4.25-5.33], physician-diagnosed asthma (OR
      5.29, CI 95% 4.49-6.24) and occupational exposure to dust, gases and fumes (OR
      1.49, CI 95% 1.30-1.72) were determinants for AR. Prevalence of chronic nasal
      congestion was 16.1% and of chronic rhinorrhea 14.1%. CONCLUSIONS: As a basis for
      understanding the disease, as well as in planning and prioritizing health-care
      resources, the study provides information about the current prevalence and
      determinants of self-reported AR and chronic nasal symptoms. Further, comparing
      with previous studies, the present study suggests that a plateau in the
      prevalence of AR may have been reached in Sweden.

PMID- 21848958
TI  - The association between alcohol consumption patterns and adherence to food
      consumption guidelines.
AB  - OBJECTIVE: To examine the association between alcohol consumption patterns and
      adherence to major food consumption guidelines in adults in Spain. METHODS:
      Telephone survey of 12,037 persons, representative of the population age 18 to 64
      years in the region of Madrid, conducted from 2000 to 2005. The threshold between
      average moderate and excessive drinking was 40 g alcohol/d in men and 24 g/d in
      women. Binge drinking was defined as intake of >=80 g alcohol in men and >=60 g
      in women during 1 drinking session in the last 30 days. Food consumption was
      measured with a 24-hour recall. Statistical analyses were performed using
      logistic regression and adjusted for the main confounders. RESULTS: In total,
      4.3% of study participants were excessive drinkers and 10.3% binge drinkers; 6.5%
      preferred spirits and 24.2% drank with meals. In comparison with never drinking,
      average moderate drinking with binge drinking was associated with excessive meat
      consumption (>1 serving/d). Excessive alcohol consumption without binge drinking
      was associated with insufficient intake of milk products (<2 servings/d) and
      excessive consumption of meat, fish, and eggs (>2 servings/d). Excessive drinkers
      with binge drinking more often did not meet the guidelines on consumption of
      fruit and vegetables (<3 servings/d), milk products, and meat. Excessive
      drinkers, with and without binge drinking, were more likely to skip a meal,
      especially breakfast. Consumption mainly of spirits was associated with
      insufficient fruit and vegetable consumption, and with skipping a meal. Finally,
      drinking at mealtimes was associated with poor adherence to most of the food
      consumption guidelines. No dietary differences between men and women were found
      in relation to alcohol consumption. CONCLUSIONS: Average excessive alcohol
      consumption, binge drinking, preference for spirits, and drinking alcohol at
      mealtimes are associated with poor adherence to major food consumption
      guidelines.

PMID- 21848957
TI  - Commentary on Rossheim and Thombs (2011): artificial sweeteners, caffeine, and
      alcohol intoxication in bar patrons.
AB  - BACKGROUND: This commentary discusses the paper by Rossheim and Thombs (Alcohol
      Clin Exp Res 35, 2011), which examined the relationship between type of alcohol
      mixer (regular caffeinated cola, diet caffeinated cola, energy drink, or no
      mixer) and breath alcohol readings in bar patrons. METHODS: The significance of
      the findings of this study and new unaddressed questions for the field are
      discussed. RESULTS: Rossheim and Thombs (2011) reported that breath alcohol
      concentration readings were highest when patrons reported the consumption of
      caffeine mixers that were artificially sweetened (i.e., diet cola), after
      adjusting for potential confounds. Women were more likely to consume diet cola
      caffeinated mixed drinks. CONCLUSIONS: The findings from this field study raise
      several new interesting questions. Given the reported gender difference in
      consumption of diet cola-caffeinated mixed drinks, more research is needed
      regarding gender differences in gastric emptying time for alcoholic beverages
      mixed with artificially sweetened versus sucrose sweetened caffeinated drinks. In
      addition, the recent explosion in the energy drink market has resulted in the
      availability of sugar-free or diet versions of most energy drink products. The
      implications of mixing diet energy drinks with alcohol are unknown.

PMID- 21848959
TI  - Alcohol has a dose-related effect on parasympathetic nerve activity during sleep.
AB  - BACKGROUND: The aim of this study was to identify the acute effects of ethanol on
      the relationship between sleep and heart rate variability (HRV) during sleep.
      METHODS: Ten healthy male university students were enrolled in this study. An
      alcoholic beverage was given to each subject at a dosage of 0 (control), 0.5 (low
      dose: LD), or 1.0 g (high dose: HD) of pure ethanol/kg of body weight. All
      experiments were performed at 3-week intervals. On the day of the experiment, a
      Holter electrocardiogram was attached to the subject for a 24-hour period, and
      the subject was instructed to drink the above-described dosage of alcoholic
      beverage 100 minutes before going to bed; polysomnography was then performed for
      8 hours. Power spectral analysis of the HRV was performed using the maximum
      entropy method, and the low- (LF: 0.04 to 0.15 Hz) and high-frequency (HF: 0.15
      to 0.4 Hz) components along with LF/HF ratio were calculated. RESULTS: As alcohol
      consumption increased, the heart rate increased and the spectral power of HRV
      measured at each frequency range decreased. Higher doses of ethanol also
      increased the LF/HF ratio compared with the measured ratio of the control group.
      CONCLUSIONS: Acute ethanol intake inhibits parasympathetic nerve activity and
      results in predominance of sympathetic nerve activity during sleep, in a dosage
      dependent manner. The results of this study suggest that ethanol interferes with
      the restorative functions of sleep.

PMID- 21848960
TI  - Brain-derived neurotrophic factor serum levels in alcohol-dependent subjects 6
      months after alcohol withdrawal.
AB  - BACKGROUND: Diagnosing alcohol dependence is based on clinical signs and on the
      measured levels of biological markers of alcohol consumption. However, these
      markers are neither sufficiently sensitive and nor specific enough to
      definitively determine alcohol dependence. The neuroadaptive changes associated
      with alcohol dependence involve markers such as brain-derived neurotrophic factor
      (BDNF), which regulate neuronal plasticity. Serum levels of BDNF have been
      reported to decrease during alcohol dependence and may be restored to normal soon
      after alcohol is withdrawn. However, the long-term relationship between serum
      BDNF levels and abstinence status is unknown. METHODS: We investigated serum BDNF
      levels in 101 abstinent and relapsing alcohol-dependent subjects at the moment of
      hospitalization for alcohol withdrawal (M0) and 6 months later (M6) and compared
      them to the serum BDNF levels of 41 nondependent subjects. The BDNF levels of the
      alcohol-dependent subjects were compared to their serum gamma glutamyl
      transferase (GGT) levels, mean corpuscular volume (MCV) values, and their score
      on the Beck Depression Inventory (BDI) questionnaire. RESULTS: Forty-four percent
      of the alcohol-dependent participants remained abstinent during the 6 months
      following alcohol detoxification. Serum BDNF levels of the abstinent group at M6
      were significantly higher than those of the original group of alcohol-dependent
      subjects at M0 (p = 0.034). Only the abstinent group had higher BDNF levels than
      the control group (p < 0.001). Serum BDNF levels increased to a greater extent in
      the abstinent group than in the nonabstinent group (p = 0.016). No correlations
      were found between serum BDNF levels and GGT level, MCV value, or BDI score.
      CONCLUSIONS: Our data confirm that serum BDNF levels do not correlate with either
      chronic alcohol consumption or peripheral toxicity but may be linked to neuronal
      aspects of alcohol consumption and dependence. The increased serum levels of BDNF
      may reflect the concomitant activation of BDNF synthesis that accompanies the
      neuronal remodeling triggered by alcohol withdrawal and suggests that BDNF
      synthesis may have a role in the long-term maintenance of abstinence. Monitoring
      the serum BDNF levels of alcoholics undergoing treatment could help to
      characterize alcohol dependence profiles and predict relapse.

PMID- 21848961
TI  - Gender differences in the effects of ADH1B and ALDH2 polymorphisms on alcoholism.
AB  - BACKGROUND: Gender differences are known to exist in the prevalence,
      characteristics, and course of alcohol dependence. Elucidating gender differences
      in the characteristics of alcohol dependence is important in gender-based
      medicine and may improve treatment outcomes. Many studies have shown that genetic
      factors are associated with the risk of alcohol dependence in both genders.
      Polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2
      (ALDH2) are strong genetic determinants of alcohol dependence. This study aimed
      to clarify gender differences in the effects of ADH1B and ALDH2 polymorphism on
      the development of alcohol dependence. METHODS: Subjects were 200 female
      alcoholics and 415 male alcoholics hospitalized in Kurihama Alcoholism Center.
      Clinical information and background data were obtained by chart review. ALDH2 and
      ADH1B genotyping was performed by the polymerase chain reaction-restriction
      fragment length polymorphism method. RESULTS: The onset age of female alcoholics
      with inactive ALDH2 genotype was significantly lower than those with active ALDH2
      genotype, but the onset age did not differ between the inactive and active ALDH2
      group in male alcoholics. The difference in onset age between the ADH1B genotype
      groups did not reach significant levels. The prevalence of comorbid psychiatric
      disorders, including major depression, eating disorder, panic disorder, and
      borderline personality disorder, was significantly higher in female alcoholics
      with inactive ALDH2 or superactive ADH1B than in those with active ALDH2 or
      normal ADH1B. CONCLUSIONS: ALDH2 polymorphism appears to have contrasting effects
      on the development of alcoholism in women and men. One possible reason for this
      gender difference may be the high prevalence of psychiatric comorbidities in
      female alcoholics with inactive ALDH2.

PMID- 21848962
TI  - Using coral disease prevalence to assess the effects of concentrating tourism
      activities on offshore reefs in a tropical marine park.
AB  - Concentrating tourism activities can be an effective way to closely manage high
      use parks and minimize the extent of the effects of visitors on plants and
      animals, although considerable investment in permanent tourism facilities may be
      required. On coral reefs, a variety of human-related disturbances have been
      associated with elevated levels of coral disease, but the effects of reef-based
      tourist facilities (e.g., permanent offshore visitor platforms) on coral health
      have not been assessed. In partnership with reef managers and the tourism
      industry, we tested the effectiveness of concentrating tourism activities as a
      strategy for managing tourism on coral reefs. We compared prevalence of brown
      band disease, white syndromes, black band disease, skeletal eroding band, and
      growth anomalies among reefs with and without permanent tourism platforms within
      the Great Barrier Reef Marine Park. Coral diseases were 15 times more prevalent
      at reefs with offshore tourism platforms than at nearby reefs without platforms.
      The maximum prevalence and maximum number of cases of each disease type were
      recorded at reefs with permanently moored tourism platforms. Diseases affected 10
      coral genera from 7 families at reefs with platforms and 4 coral genera from 3
      families at reefs without platforms. The greatest number of disease cases
      occurred within the spatially dominant acroporid corals, which exhibited 18-fold
      greater disease prevalence at reefs with platforms than at reefs without
      platforms. Neither the percent cover of acroporids nor overall coral cover
      differed significantly between reefs with and without platforms, which suggests
      that neither factor was responsible for the elevated levels of disease.
      Identifying how tourism activities and platforms facilitate coral disease in
      marine parks will help ensure ongoing conservation of coral assemblages and
      tourism.

PMID- 21848963
TI  - Erythrocytapheresis versus phlebotomy in the initial treatment of HFE
      hemochromatosis patients: results from a randomized trial.
AB  - BACKGROUND: Standard treatment of newly diagnosed HFE hemochromatosis patients is
      phlebotomy. Erythrocytapheresis provides a new therapeutic modality that can
      remove up to three times more red blood cells per single procedure and could thus
      have a clinical and economic benefit. STUDY DESIGN AND METHODS: To compare the
      number of treatment procedures between erythrocytapheresis and phlebotomy needed
      to reach the serum ferritin (SF) target level of 50 ug/L, a two-treatment-arms,
      randomized trial was conducted in which 38 newly diagnosed patients homozygous
      for C282Y were randomly assigned in a 1:1 ratio to undergo either
      erythrocytapheresis or phlebotomy. A 50% decrease in the number of treatment
      procedures for erythrocytapheresis compared to phlebotomy was chosen as the
      relevant difference to detect. RESULTS: Univariate analysis showed a
      significantly lower mean number of treatment procedures in the
      erythrocytapheresis group (9 vs. 27; ratio, 0.33; 95% confidence interval [CI],
      0.25-0.45; Mann-Whitney p < 0.001). After adjustments for the two important
      influential factors initial SF level and body weight, the reduction ratio was
      still significant (0.43; 95% CI, 0.35-0.52; p < 0.001). Cost analysis showed no
      significant difference in treatment costs between both procedures. The costs
      resulting from productivity loss were significantly lower for the
      erythrocytapheresis group. CONCLUSION: Erythrocytapheresis is highly effective
      treatment to reduce iron overload and from a societal perspective might
      potentially also be a cost-saving therapy.

PMID- 21848964
TI  - Combining measures of dispersal to identify conservation strategies in fragmented
      landscapes.
AB  - Understanding the way in which habitat fragmentation disrupts animal dispersal is
      key to identifying effective and efficient conservation strategies. To
      differentiate the potential effectiveness of 2 frequently used strategies for
      increasing the connectivity of populations in fragmented landscapes-corridors and
      stepping stones-we combined 3 complimentary methods: behavioral studies at
      habitat edges, mark-recapture, and genetic analyses. Each of these methods
      addresses different steps in the dispersal process that a single intensive study
      could not address. We applied the 3 methods to the case study of Atrytonopsis new
      species 1, a rare butterfly endemic to a partially urbanized stretch of barrier
      islands in North Carolina (U.S.A.). Results of behavioral analyses showed the
      butterfly flew into urban and forested areas, but not over open beach; mark
      recapture showed that the butterfly dispersed successfully through short
      stretches of urban areas (<500 m); and genetic studies showed that longer
      stretches of forest (>5 km) were a dispersal barrier, but shorter stretches of
      urban areas (<=5 km) were not. Although results from all 3 methods indicated
      natural features in the landscape, not urbanization, were barriers to dispersal,
      when we combined the results we could determine where barriers might arise:
      forests restricted dispersal for the butterfly only when there were long
      stretches with no habitat. Therefore, urban areas have the potential to become a
      dispersal barrier if their extent increases, a finding that may have gone
      unnoticed if we had used a single approach. Protection of stepping stones should
      be sufficient to maintain connectivity for Atrytonopsis new species 1 at current
      levels of urbanization. Our research highlights how the use of complementary
      approaches for studying animal dispersal in fragmented landscapes can help
      identify conservation strategies.

PMID- 21848965
TI  - Use of computed tomography adrenal gland measurement for differentiating ACTH
      dependence from ACTH independence in 64 dogs with hyperadenocorticism.
AB  - BACKGROUND: The measurement of adrenal gland size on computed tomography (CT)
      scan has been proposed for the etiological diagnosis of hyperadrenocorticism
      (HAC) in dogs. Symmetric adrenal glands are considered to provide evidence for
      ACTH-dependent hyperadrenocorticism (ADHAC), whereas asymmetry suggests ACTH
      independent hyperadrenocorticism (AIHAC). However, there are currently no
      validated criteria for such differentiation. OBJECTIVE: The aim of this
      retrospective study was to compare various adrenal CT scan measurements and the
      derived ratios in ADHAC and AIHAC cases, and to validate criteria for
      distinguishing between these conditions in a large cohort of dogs. ANIMALS: Sixty
      four dogs with HAC (46 ADHAC, 18 AIHAC). METHODS: Dogs with confirmed HAC and
      unequivocal characterization of its origin were included. Linear measurements of
      adrenal glands were made on both cross-sectional and reformatted images. RESULTS:
      An overlap was systematically observed between the AIHAC and ADHAC groups for all
      measurements tested. Overlaps also were observed for ratios tested. For the
      maximum adrenal diameter ratio derived from reformatted images (rADR), only 1/18
      AIHAC dogs had a rADR within the range for ADHAC. For a threshold of 2.08, the
      95% confidence intervals for estimated sensitivity and specificity extended from
      0.815 to 1.000 and from 0.885 to 0.999, respectively, for AIHAC diagnosis.
      CONCLUSION AND CLINICAL IMPORTANCE: Measurements from cross-sectional or
      reformatted CT scans are of little use for determining the origin of HAC.
      However, rADR appears to distinguish accurately between ADHAC and AIHAC, with a
      rADR > 2.08 highly suggestive of AIHAC.

PMID- 21848966
TI  - Echocardiographic and tissue Doppler imaging alterations associated with
      spontaneous canine systemic hypertension.
AB  - BACKGROUND: Feline systemic arterial hypertension (SHT) is associated with a wide
      spectrum of left ventricular (LV) geometric patterns as well as diastolic, and to
      a lesser extent, systolic myocardial dysfunction. However, little is known about
      SHT-related cardiac changes in dogs. HYPOTHESIS: SHT in dogs is responsible for
      morphological and functional cardiac alterations. ANIMALS: Thirty dogs with
      spontaneous untreated SHT and 28 age- and body weight-matched healthy dogs as
      controls. METHODS: Prospective observational study. Conventional echocardiography
      and 2-dimensional color tissue Doppler imaging were performed in SHT dogs by
      trained observers and compared with controls. RESULTS: Forty-seven percent of SHT
      dogs (14/30) had diffuse concentric hypertrophy. None had left atrial dilatation
      and 10/30 (33%) had aortic insufficiency (AoI) associated with proximal aortic
      dilatation. Longitudinal diastolic left ventricular free wall (LVFW) motion was
      altered in all SHT dogs at the base (early to late diastolic wave ratio, E/A =
      0.5 +/- 0.1 versus 1.3 +/- 0.3 for controls, P < .0001) and the apex (E/A = 1.6
      +/- 1.7 versus 3.9 +/- 3.1, P < .05). Longitudinal motion of the interventricular
      septum at the base (E/A = 0.7 +/- 0.4 versus 1.1 +/- 0.1, P < .01) and radial
      LVFW motion in the subendocardium (E/A = 0.9 +/- 0.5 versus 1.6 +/- 0.3, P < .01)
      were also altered in dogs with SHT. Longitudinal LVFW systolic velocities and
      gradients were also significantly decreased (P < .05) in SHT dogs. CONCLUSION AND
      CLINICAL IMPORTANCE: As in SHT in cats, SHT in dogs is associated with myocardial
      dysfunction independently of the presence of myocardial hypertrophy. However,
      unlike feline SHT, it results in a homogeneous LV geometric pattern with a
      relatively high prevalence of AoI.

PMID- 21848967
TI  - Degenerative myelopathy in a Bernese Mountain Dog with a novel SOD1 missense
      mutation.

PMID- 21848968
TI  - Outcomes after major or bidirectional ABO-mismatched allogeneic hematopoietic
      progenitor cell transplantation after pretransplant isoagglutinin reduction with
      donor-type secretor plasma with or without plasma exchange.
AB  - BACKGROUND: Major ABO mismatch in hematopoietic progenitor cell transplantation
      (HPCT) is associated with a range of immunohematologic consequences including
      progenitor cell infusion (PCI)-related hemolysis, delayed red blood cell
      engraftment, and pure red cell aplasia (PRCA). Although pretransplant (recipient)
      isoagglutinin reduction may be associated with decreased immunohematologic
      complications in this setting, there is no consensus with respect to strategies
      for isoagglutinin reduction. STUDY DESIGN AND METHODS: This observational study
      assessed the efficacy of a standardized pretransplant isoagglutinin reduction
      strategy incorporating donor-type secretor plasma infusions with or without
      plasma exchange to prevent PCI-associated hemolysis and PRCA in major or
      bidirectional ABO-mismatched peripheral blood HPCT. All major or bidirectional
      ABO-mismatched HPCTs performed between 1999 and 2010 were identified from an
      institutional database. Immunohematologic outcomes were determined
      retrospectively by review of individual medical records. RESULTS: In total 110
      major or bidirectional ABO-mismatched HPCTs had been performed. No patient
      developed hemolysis after PCI. With respect to PRCA incidence, 16 patients (15%)
      were excluded due to early mortality and three (3%) due to incomplete data; of
      the remaining 91 patients, five (5%) developed PRCA. Patients with PRCA had
      significantly higher pretransplant isoagglutinin titers (p = 0.0001) compared to
      those who did not develop PRCA. CONCLUSIONS: Use of a standardized pretransplant
      isoagglutinin reduction strategy including donor-type secretor plasma infusions
      is both safe and efficient in preventing PCI-associated hemolysis and is
      associated with low rates of posttransplant PRCA.

PMID- 21848969
TI  - Assessment of donor fear enhances prediction of presyncopal symptoms among
      volunteer blood donors.
AB  - BACKGROUND: Fear is an important contributor to the risk of presyncopal reactions
      to blood donation. However, concern that asking donors about their fears may
      increase the risk of reactions is a potential impediment to incorporating fear
      assessment into donor screening. STUDY DESIGN AND METHODS: Before donation,
      participants responded to a series of questions that either did (n = 488) or did
      not (n = 494) include questions related to fear of seeing blood drawn.
      Immediately after donation all participants provided ratings of presyncopal
      reactions. RESULTS: Among those asked predonation fear questions, fear was most
      strongly related to presyncopal symptoms when compared against other donor
      characteristics (e.g., age, number of prior donations, body mass index, estimated
      blood volume, blood pressure, and pulse). However, Mann-Whitney U tests revealed
      that being asked about fear before donation was not associated with higher
      reports of presyncopal reactions for the sample as a whole, nor among novice
      donors. Further, regression analyses indicated that fear remained a significant
      predictor of presyncopal reactions in final models that included age and number
      of prior donations as significant predictors. CONCLUSION: Predonation assessment
      of fear of blood draws may help to identify donors who are most likely to benefit
      from brief interventions designed to enhance donor coping, reduce risk of
      presyncopal reactions, and increase donor retention.

PMID- 21848970
TI  - Diagnostic luciferase reporter phage assay for active and non-replicating
      persistors to detect tubercle bacilli from sputum samples.
AB  - Diagnosis of latent tuberculosis infection is a myth for want of a simple, direct
      tool. Simulation of hypoxic environment was done to create a novel hypothetical
      model for persistence using processed sputum samples. The adaptation of tubercle
      bacilli to hypoxic environment seems to be influenced by pre-existing clinical
      status of the patients at the time of sputum collection, resulting in varied
      growth pattern. Bacilli from 36 samples did not get adapted to latency of which
      15 samples were from patients in whom the disease was well established and the
      tubercle bacilli in them probably did not experience any stress whatsoever.
      Similarly, 10 of the 37 samples showing the presence of cultivable cells in both
      aerobic and anaerobic conditions were from patients who had relapsed. The bacilli
      in these samples had been probably experiencing stress and thus were ready to
      adapt to the hypoxic environment. Diagnostic luciferase reporter phage assay for
      non-replicating persistors (DLRPA-NRP) identified 30 additional positives which
      failed to grow on Lowenstein-Jensen medium. Presence of viable bacilli in these
      samples was confirmed by reverse transcriptase-PCR (RT-PCR) for 16S rRNA
      indicating either the improved sensitivity of the assay to detect actively
      growing bacilli or its ability to detect non-replicating persistors. The utility
      of LRP assay to detect both dormant and active tubercle bacilli was explored in
      this work and was optimized using lysis inhibition to diagnose tuberculosis with
      rapidity, improved sensitivity and specificity. DLRPA-NRP, a rapid growth based
      assay is thus developed to detect both dormant and actively growing tubercle
      bacilli.

PMID- 21848971
TI  - Enhanced isolation of Legionella species from composted material.
AB  - Legionella pneumophila and Legionella species were isolated from composted
      material when freshly prepared buffered charcoal yeast extract (BCYE) was
      supplemented with glycine (1.5 g/L), polymyxin B sulfate (40 000 IU/L),
      vancomycin hydrochloride (0.5 mg/L) and cycloheximide (40 mg/L) (GVPC medium) and
      Modified Wadowsky-Yee (MWY) (Oxoid, Cambridge, UK) plates were used for
      cultivation, but not with commercially sourced pre-poured GVPC and MWY plates
      (Oxoid). Legionella cincinnatiensis and pathogenic L. pneumophila serogroup (Sg)
      1 Benidorm and France/Allentown were identified, as well as a non-typeable (NT)
      strain of L. pneumophila. As most laboratories no longer produce their own media,
      this may contribute to the lack of positive cultures from composted material. The
      antigenicity of the NT strain is discussed.

PMID- 21848972
TI  - Comparative detection of enterovirus RNA in cerebrospinal fluid: GeneXpert system
      vs. real-time RT-PCR assay.
AB  - Enteroviruses (EVs) constitute the most common cause of aseptic meningitis in
      both children and adults. Molecular techniques have now been recognized as the
      reference standard for the diagnosis of EV infections, and the rapidity of the
      molecular diagnosis of EV meningitis has been shown to be a determining factor in
      the management of patients. The rapid documentation of EV RNA in cerebrospinal
      fluid (CSF) is key to adapting patient management and the therapeutic regimen. To
      shorten the time needed for virological documentation, we implemented EV RNA
      detection in two point-of-care (POC) laboratories. Here, we present the results
      of the POC detection of EV RNA with the Xpert EV kit on the GeneXpert integrated
      system, and a comparison with the real-time RT-PCR (rtRT-PCR) assay routinely
      used in the core virology laboratory. From January to September 2009, a total of
      310 CSF samples were tested. The rtRT-PCR gave 81 positive, 225 negative and four
      'indeterminate' results. POC results were concordant in 81.6% (253/310). Most of
      the discrepancies consisted of 'indeterminate' results at the POC level (16%).
      Calculated performances (excluding the indeterminate results) of the Xpert EV kit
      on the GeneXpert system in POC settings were 100%, 98.9%, 97.6% and 100% for
      Sensibility, Specificity, positive predictive value and negative predictive
      value, respectively. Taken together, these results indicate that the
      implementation of POC detection of EV RNA can provide robust results in <4 h, and
      may have a significant impact on patient management, therapeutic attitude, and
      hospitalization costs.

PMID- 21848973
TI  - The scent of senescence: sexual signalling and female preference in house mice.
AB  - Sexual signals are expected to be costly to produce and maintain, thus ensuring
      that only males in good condition can sustain their expression at high levels.
      When males reach senescence they lose physiological function and condition, which
      could constrain their ability to invest in costly sexual signals, decreasing
      their attractiveness to mates. Furthermore, females may have evolved mating
      preferences that cause avoidance of senesced males to enhance fertilization
      success and viability of offspring. Among mammals, the size of antlers and other
      weapons can decrease with senescence, but changes in olfactory sexual signals
      have been largely unexplored. We examined changes in olfactory signals with
      senescence in house mice (Mus musculus domesticus), where males excrete volatile
      and involatile molecules in scent marks that elicit behavioural and priming
      responses in females. Compared to middle-aged males, the urine of senesced males
      contained a lower concentration of involatile signalling proteins (major urinary
      proteins or MUPs), and associated volatiles that bind to these proteins. The
      reduced intensity of male scent will affect the longevity of scent signals
      deposited in the environment and, accordingly, females were less attracted to
      urine from senesced males deposited 12 h previously. Females also discriminated
      against senesced males encountered behind a mesh barrier. These results reveal
      that investment in olfactory signalling is reduced during senescence and suggest
      that senesced males and their scent may be less attractive to females.

PMID- 21848974
TI  - Lactobacillus rhamnosus administration causes sepsis in a cardiosurgical patient-
      is the time right to revise probiotic safety guidelines?
AB  - A 24-year-old female patient developed sepsis resulting from preoperative
      administration of probiotics following an aortic valve replacement. Blood
      cultures revealed the causative agent to be the probiotic Lactobacillus
      rhamnosus, which has recently been implicated as an emerging aetiology of
      infection in those taking probiotics. In the past few years, probiotic use in
      hospitals has increased greatly. However, there is growing global evidence that
      the use of probiotics in patients with organ failure, immunocompromised status
      and dysfunctional gut barrier mechanisms can cause infections. This and other
      reports show the importance of establishing generally recognized safety
      guidelines.

PMID- 21848975
TI  - Travel-related imported infections in Europe, EuroTravNet 2009.
AB  - The aim of this study was to investigate travel-associated morbidity in European
      travellers in 2009 in comparison with 2008, with a particular emphasis on
      emerging infectious diseases with the potential for introduction into Europe.
      Diagnoses with demographic, clinical and travel-related predictors of disease
      from ill returning travelers presenting to 12 core EuroTravNet sites from January
      to December 2009 were analysed. A total of 6392 patients were seen at EuroTravNet
      core sites in 2009, as compared with 6957 in 2008. As compared with 2008, there
      was a marked increase in the number of travellers exposed in North America and
      western Europe. Respiratory illnesses, in particular pandemic A(H1N1) influenza,
      influenza-like syndromes, and tuberculosis, were also observed more frequently. A
      significant increase in reported dengue cases in 2009 as compared with 2008 was
      observed (n = 172, 2.7% vs. n = 131, 1.90%) (p 0.002). The numbers of malaria and
      chikungunya cases were also increasing, although not significantly. Two deaths
      were recorded: visceral leishmaniasis and sepsis in a Sudanese migrant, and
      Acinetobacter sp. pneumonia in a patient who had visited Spain. This is the most
      comprehensive study of travel-related illness in Europe in 2009 as compared with
      2008. A significant increase in travel-related respiratory and vector-borne
      infections was observed, highlighting the potential risk for introduction of
      these diseases into Europe, where competent vectors are present. The number of
      traveller deaths is probably underestimated. The possible role of the travellers
      in the emergence of infectious diseases of public health concern is highlighted.

PMID- 21848976
TI  - High prevalence of community-acquired norovirus gastroenteritis among
      hospitalized children: a prospective study.
AB  - Acute gastroenteritis (AGE) causes significant morbidity, especially in young
      children, and frequently requires hospitalization even in developed countries.
      Surveillance studies of AGE are important to determine the prevalence and variety
      of bacterial and viral pathogens, to initiate targeted preventive measures, such
      as vaccine programmes, and to monitor its impact. A prospective study was
      conducted in children <5 years old, admitted with AGE between April 2006 and
      April 2007 to the Virgen del Rocio University Hospital, Seville, Spain.
      Demographic and clinical data were collected and patients followed-up after
      hospital discharge. A stool sample from each child was screened for
      enteropathogenic bacteria and tested by reverse transcription polymerase chain
      reaction for rotavirus, astrovirus, norovirus and sapovirus and by the
      immunochromatographic method for enteric adenoviruses. Norovirus was the most
      common pathogen in hospitalized children, being detected in 27%, followed by
      rotavirus 21%. Mixed infection occurred in nearly 20% of all norovirus infections
      and was most commonly associated with Salmonella spp. Rotavirus infection was
      associated with an overall higher severe clinical score compared with norovirus
      infection. Lactose intolerance was observed in 29 children (7.5%) and most
      commonly due to rotavirus infection (p <0.001). Seizures were reported in four
      children. Norovirus was the commonest cause of AGE in hospitalized children <5
      years during 2006-2007 in Seville, Spain. The use of these molecular techniques
      should be included routinely for the surveillance of sporadic cases and outbreaks
      of norovirus AGE in children attending hospitals as well as healthcare centres.

PMID- 21848977
TI  - Differing risk factors for vancomycin-resistant and vancomycin-sensitive
      enterococcal bacteraemia.
AB  - Enterococcus is an important cause of bacteraemia. Previous epidemiological
      studies examining risk factors for enterococcal bacteraemia have used traditional
      case-control study designs, which can be potentially biased. This case-case
      control study examining risk factors for enterococcal bacteraemia was conducted
      over 10 years (January 2000 to December 2009) in a tertiary, university
      affiliated hospital. There were 440 episodes of enterococcal bacteraemia, 80 of
      which were caused by vancomycin-resistant Enterococcus (VRE). Two multivariable
      models were generated, comparing VRE and vancomycin-susceptible Enterococcus
      (VSE) with the same control group. VRE bacteraemia was associated with central
      venous catheter use (OR 11.6, 95% CI 2.6-51.5), neutropenia (OR 16.9, 95% CI 2.4
      120.2), and allogenic bone marrow transplantation (OR 18.0, 95% CI 2.4-133.4). In
      contrast, VSE bacteraemia risk factors included: age (OR 1.0, 95% CI 1.0-1.1),
      exposure to metronidazole (OR 8.7, 95% CI 1.7-43.5), and gastrointestinal disease
      (OR 6.4, 95% CI 1.2-34.5). Meropenem use decreased the risk of VSE bacteraemia
      (OR 0.3, 95% CI 0.1-0.9). Hypoalbuminaemia was the only factor identified in both
      models (VRE, OR 6.0, 95% CI 1.7-21.1; VSE, OR 3.3, 95% CI 1.4-7.7). The absence
      of substantial overlap of risk factors for VRE and VSE argues in favour of
      differences in pathogenesis. These data suggest that environmental sources are
      more important in VRE bacteraemia. Endogenous sources, particularly the
      gastrointestinal tract, play a pivotal role in VSE bacteraemia. This study
      highlights the importance of infection control protocols to reduce the risk of
      VRE bacteraemia.

PMID- 21848978
TI  - Approximate Bayesian computation reveals the factors that influence genetic
      diversity and population structure of foxsnakes.
AB  - Contemporary geographical range and patterns of genetic diversity within species
      reflect complex interactions between multiple factors acting across spatial and
      temporal scales, and it is notoriously difficult to disentangle causation. Here,
      we quantify patterns of genetic diversity and genetic population structure using
      mitochondrial DNA sequences (101 individuals, cytochrome b) and microsatellites
      (816 individuals, 12 loci) and use Approximate Bayesian computation methods to
      test competing models of the demographic history of eastern and western
      foxsnakes. Our analyses indicate that post-glacial colonization and past
      population declines, probably caused by the infilling of deciduous forest and
      cooler temperatures since the mid-Holocene, largely underpin large-scale genetic
      patterns for foxsnakes. At finer geographical scales, our results point to more
      recent anthropogenic habitat loss as having accentuated genetic population
      structure by causing further declines and fragmentation.

PMID- 21848979
TI  - The relative contribution of band number to phylogenetic accuracy in AFLP data
      sets.
AB  - We examined the effect of increasing the number of sampled amplified fragment
      length polymorphism (AFLP) bands to reconstruct an accurate and well-supported
      AFLP-based phylogeny. In silico AFLP was performed using simulated DNA sequences
      evolving along balanced and unbalanced model trees with recent, uniform and
      ancient radiations and average branch lengths (from the most internal node to the
      tip) ranging from 0.02 to 0.05 substitutions per site. Trees were estimated by
      minimum evolution (ME) and maximum parsimony (MP) methods from both DNA sequences
      and virtual AFLP fingerprints. The comparison of the true tree with the estimated
      AFLP trees suggests that moderate numbers of AFLP bands are necessary to recover
      the correct topology with high bootstrap support values (i.e. >70%). Fewer
      numbers of bands are necessary for shorter tree lengths and for balanced than for
      unbalanced tree topologies. However, branch length estimation was rather
      unreliable and did not improve substantially after a certain number of bands were
      sampled. These results hold for different levels of genome coverage and number of
      taxa analysed. In silico AFLP using bacterial genomic DNA sequences recovered a
      well-supported tree topology that mirrored an empirical phylogeny based on a set
      of 31 orthologous gene sequences when as few as 263 AFLP bands were scored. These
      results suggest that AFLPs may be an efficient alternative to traditional DNA
      sequencing for accurate topology reconstruction of shallow trees when not very
      short ancestral branches exist.

PMID- 21848980
TI  - Hyperhidrosis plantaris - a randomized, half-side trial for efficacy and safety
      of an antiperspirant containing different concentrations of aluminium chloride.
AB  - BACKGROUND: Primary focal hyperhidrosis plantaris can cause impairment in social,
      physical, leisure and occupational activities. Topical treatment with aluminium
      chloride is the first-line treatment. The aim of this trial was to evaluate
      efficacy and safety of two different concentrations of aluminium chloride hexa
      hydrate (12.5%, 30%) for 6 weeks. PATIENTS AND METHODS: 20 volunteers with
      hyperhidrosis plantaris were included. Efficacy was evaluated using a clinical
      rating scale of the hyperhidrosis level and qualitative assessments including
      Minor's (iodine-starch) test and a standardized sniff test. Furthermore a patient
      questionnaire and measurements of skin surface pH were done to evaluate the
      subjective assessments and side effects. RESULTS: The hyperhidrosis level
      significantly decreased in both concentrations. There were no differences in
      tolerability regarding the skin surface pH and the patient questionnaires. In
      addition the hidrotic areas decreased after application of both products and the
      sniff test improved. CONCLUSION: Topical application of an antiperspirant
      containing aluminium chloride reduced sweat production in plantar hyperhidrosis
      significantly. As both 12.5% and 30% were efficacious and safe, we would
      recommend 12.5% for outpatient treatment.

PMID- 21848981
TI  - Paraneoplastic dermatomyositis associated with metastatic melanoma.

PMID- 21848982
TI  - Root hair development involves asymmetric cell division in Brachypodium
      distachyon and symmetric division in Oryza sativa.
AB  - * The root epidermis of most angiosperms comprises hair (H) cells and nonhair (N)
      cells. H cells are shorter than N cells in grasses (Poaceae). * The aim of this
      study was to determine the developmental basis for differences in H and N cell
      size in the grasses Brachypodium distachyon and Oryza sativa. * We show that
      cytokinesis in the last cell division in each epidermal file is asymmetric in B.
      distachyon. The smaller daughter cell becomes an H cell and the larger cell forms
      an N cell. By contrast, asymmetric cytokinesis does not occur during H cell and N
      cell development in O. sativa and the differences in size arise because there is
      more cell expansion in N cells than in H cells after root hair initiation. * The
      different sizes of mature H and N cells result from cell division asymmetry in B.
      distachyon but different rates of cell expansion in O. sativa. We hypothesize
      that the mechanism that includes asymmetric cytokinesis during the development of
      H and N cells evolved among the Pooideae or ancestors of this subfamily.

PMID- 21848983
TI  - Reconstruction of the helical rim via postauricular U-shaped flap.

PMID- 21848984
TI  - Does predation result in adult sex ratio skew in a sexually dimorphic insect
      genus?
AB  - Theory proposes that sexually dimorphic, polygynous species are at particularly
      high risk of sex-biased predation, because conspicuous males are more often
      preyed upon compared to females. We tested the effects of predation on population
      sex ratio in a highly sexually dimorphic insect genus (Hemideina). In addition,
      introduction of a suite of novel mammalian predators to New Zealand during the
      last 800 years is likely to have modified selection pressures on native tree
      weta. We predicted that the balance between natural and sexual selection would be
      disrupted by the new predator species. We expected to see a sex ratio skew
      resulting from higher mortality in males with expensive secondary sexual
      weaponry; combat occurs outside refuge cavities between male tree weta. We took a
      meta-analytic approach using generalized linear mixed models to compare sex ratio
      variation in 58 populations for six of the seven species in Hemideina. We
      investigated adult sex ratio across these populations to determine how much
      variation in sex ratio can be attributed to sex-biased predation in populations
      with either low or high number of invasive mammalian predators. Surprisingly, we
      did not detect any significant deviation from 1 : 1 parity for adult sex ratio
      and found little difference between populations or species. We conclude that
      there is little evidence of sex-biased predation by either native or mammalian
      predators and observed sex ratio skew in individual populations of tree weta is
      probably an artefact of sampling error. We argue that sex-biased predation may be
      less prevalent in sexually dimorphic species than previously suspected and
      emphasize the usefulness of a meta-analytic approach to robustly analyse
      disparate and heterogeneous data.

PMID- 21848985
TI  - Rates of phenotypic evolution of ecological characters and sexual traits during
      the Tanganyikan cichlid adaptive radiation.
AB  - Theory suggests that sexual traits evolve faster than ecological characters.
      However, characteristics of a species niche may also influence evolution of
      sexual traits. Hence, a pending question is whether ecological characters and
      sexual traits present similar tempo and mode of evolution during periods of rapid
      ecological divergence, such as adaptive radiation. Here, we use recently
      developed phylogenetic comparative methods to analyse the temporal dynamics of
      evolution for ecological and sexual traits in Tanganyikan cichlids. Our results
      indicate that whereas disparity in ecological characters was concentrated early
      in the radiation, disparity in sexual traits remained high throughout the
      radiation. Thus, closely related Tanganyikan cichlids presented higher disparity
      in sexual traits than ecological characters. Sexual traits were also under
      stronger selection than ecological characters. In sum, our results suggest that
      ecological characters and sexual traits present distinct evolutionary patterns,
      and that sexual traits can evolve faster than ecological characters, even during
      adaptive radiation.

PMID- 21848986
TI  - Strong differences in chemical recognition cues between two closely related
      species of ants from the genus Lasius (Hymenoptera: Formicidae).
AB  - Cuticular hydrocarbons (CHCs) are increasingly recognized as important to insects
      and are used for constructing taxonomies. However, multiple parameters affect the
      expression of CHCs besides a genetic component. We propose that selection may act
      differently on the expression of CHCs, depending on the evolutionary context. To
      explore the influence of selection, the CHCs of two closely related ant species,
      Lasius niger and Lasius platythorax, were studied in a multidisciplinary
      approach. We characterized (i) CHCs and (ii) niches (through baiting, activity
      observations and foraging analysis). The species were distinct in both measures,
      although to a varying degree. Although they showed moderate niche partitioning
      along diet and environmental preferences, chemical differences were unexpectedly
      pronounced. This may be explained by divergent selection on mate recognition cues
      or by other influences on CHCs. Such striking chemical differences among closely
      related species may not be the rule and suggest that taxonomies based on CHCs
      should be interpreted cautiously; though, they remain useful tools for
      differentiating among cryptic species.

PMID- 21848987
TI  - Genetic variation for maternal effects on parasite susceptibility.
AB  - The expression of infectious disease is increasingly recognized to be impacted by
      maternal effects, where the environmental conditions experienced by mothers alter
      resistance to infection in offspring, independent of heritability. Here, we
      studied how maternal effects (high or low food availability to mothers) mediated
      the resistance of the crustacean Daphnia magna to its bacterial parasite
      Pasteuria ramosa. We sought to disentangle maternal effects from the effects of
      host genetic background by studying how maternal effects varied across 24 host
      genotypes sampled from a natural population. Under low-food conditions, females
      produced offspring that were relatively resistant, but this maternal effect
      varied strikingly between host genotypes, i.e. there were genotype by maternal
      environment interactions. As infection with P. ramosa causes a substantial
      reduction in host fecundity, this maternal effect had a large effect on host
      fitness. Maternal effects were also shown to impact parasite fitness, both
      because they prevented the establishment of the parasites and because even when
      parasites did establish in the offspring of poorly fed mothers, and they tended
      to grow more slowly. These effects indicate that food stress in the maternal
      generation can greatly influence parasite susceptibility and thus perhaps the
      evolution and coevolution of host-parasite interactions.

PMID- 21848988
TI  - Root hydraulic conductance and aquaporin abundance respond rapidly to partial
      root-zone drying events in a riparian Melaleuca species.
AB  - * Drying a portion of a root system (partial root-zone drying (PRD)) can induce
      partial stomatal closure, but this response is not always observed. We
      hypothesized that some of the variation in PRD response reflects adaptations to
      the native environment, where plants subjected to frequent PRD events may display
      a greater degree of root-level compensation. * Here, we examined PRD responses of
      Melaleuca argentea, a tree native to intermittent waterways in which PRD events
      are common. Seedlings were grown with part of their root system in soil and part
      in an aquatic compartment, mimicking conditions often observed in the field. *
      The aquatic roots initially provided two-thirds of total water uptake, but
      draining the aquatic compartment had no effect on stomatal conductance, so long
      as soil moisture remained c. 80% of field capacity. Water uptake from the soil
      compartment increased threefold within 24 h, with a corresponding transient
      threefold increase in root hydraulic conductance (L(p)), an increase in plasma
      membrane intrinsic protein 1 (PIP1) aquaporins at 24 h, and a decrease in PIP2
      aquaporins by 48 h. * Our results demonstrate that PRD can induce rapid changes
      in L(p) and aquaporin expression in roots, which may play a role in short-term
      water uptake adjustments, particularly in species adapted to heterogeneous water
      availability.

PMID- 21848989
TI  - The experience of risk as 'measured vulnerability': health screening and lay uses
      of numerical risk.
AB  - As clinical and epidemiological research turns increasingly to statistical
      probabilities in the identification and management of disease, numerous risk
      factors have emerged that are applied to individual health surveillance. However,
      the application of statistical risk is interpreted differently by lay persons
      from the way it is by public health or medical professionals. This paper examines
      the experience of being designated as at risk of a serious health condition.
      Specifically, an examination of the experiences of people with elevated blood
      cholesterol levels and men with elevated prostate-specific antigen (PSA) levels
      is presented in order to characterise the risk experience. This paper deals
      primarily with how being at risk symbolically alters health identities, with an
      introduction to the concept of measured vulnerability. Measured vulnerability
      refers to the capacity for scientifically-derived statistical measures that are
      intended to tame randomness and provide certainty in managing risk to, instead,
      produce uncertainty and anxiety in those to whom the statistic is applied.

PMID- 21848990
TI  - Disturbed development of the enteric nervous system after in utero exposure of
      selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2:
      Testing the hypotheses.
AB  - AIMS: Antidepressant use has increased in the last decade. Several studies have
      suggested a possible association between maternal antidepressant use and
      teratogenic effects. METHODS: The pharmacy prescription database IADB.nl was used
      for a cohort study in which laxative and antidiarrhoeal medication use in
      children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or
      paroxetine exposed) was compared with no antidepressant exposure. Laxatives and
      antidiarrhoeal medication use were applied as a proxy for constipation and
      diarrhoea respectively, which may be associated with disturbed enteric nervous
      system (ENS) development. RESULTS: Children exposed in utero to SSRIs (mainly
      fluoxetine and paroxetine) in the second and third trimester or to TCAs in the
      first trimester, more often received laxatives. Combined exposure to TCAs and
      SSRIs in pregnancy was associated with a 10-fold increase in laxative use. In
      utero exposure to SSRIs is not associated with antidiarrhoeal medication use
      compared with non-exposed children. In contrast, antidiarrhoeal medication use
      was significantly higher in children exposed to TCAs anytime in pregnancy.
      CONCLUSIONS: The increased laxative use after second and third trimester exposure
      to SSRIs might be explained through the inhibitory effect of the serotonin re
      uptake transporter (SERT) and because of selectivity for the 5-HT(2B) receptor
      which affects the ENS. TCA exposure during the first trimester leads to increased
      laxative use probably through inhibition of the norepinephrine transporter (NET).
      Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly
      through down-regulation of alpha2-adrenoceptors or up-regulation of the pore
      forming alpha(1c) subunit.

PMID- 21848991
TI  - Exercise and melatonin in humans: reciprocal benefits.
AB  - The aim of this review is to update the reader as to the association between
      physical exercise and melatonin, and to clarify how the melatonin rhythm may be
      affected by different types of exercise. Exercise may act as a zeitgeber,
      although the effects of exercise on the human circadian system are only now being
      explored. Depending on the time of the day, on the intensity of light, and on the
      proximity of the exercise to the onset or decline of the circadian production of
      melatonin, the consequence of exercise on the melatonin rhythm varies. Moreover,
      especially strenuous exercise per se induces an increased oxidative stress that
      in turn may affect melatonin levels in the peripheral circulation because indole
      is rapidly used to combat free radical damage. On the other hand, melatonin also
      may influence physical performance, and thus, there are mutually interactions
      between exercise and melatonin production which may be beneficial.

PMID- 21848992
TI  - Dermatitis herpetiformis presenting as digital petechiae.
AB  - We present a 15-year-old female patient with a 6-month history of recurrent
      painful petechiae on the fingers and feet. Trauma or pressure were denied, but
      she reported recurrent tonsillitis and urinary tract infections and a single
      event of bilateral scotoma. Extensive investigations (e.g., echocardiography) for
      a suspected diagnosis of septic emboli were unremarkable. Routine histopathology,
      direct and indirect immunofluorescence, and esophagogastroduodenoscopy led to the
      diagnosis of dermatitis herpetiformis. The therapeutic strategy comprised gluten
      free diet and dapsone to alleviate the symptoms. Dermatitis herpetiformis should
      be included in the differential diagnosis of palmar or plantar petechiae,
      especially when occurring in children or young adults.

PMID- 21848994
TI  - Epithelial Bmp (Bone morphogenetic protein) signaling for bulbourethral gland
      development: a mouse model for congenital cystic dilation.
AB  - The bulbourethral gland (BUG) is a male-specific organ, which secretes part of
      the semen fluid. As the BUG is located in the deep pelvic floor, its
      developmental process is still unclear. Bone morphogenetic protein (Bmp)
      signaling plays pivotal roles in various organs. However, the function of Bmp
      signaling for BUG development is still unclear. The present study aimed to
      elucidate the role of Bmp signaling in the development of the BUG. We observed
      the prominent nuclear accumulation of phosphorylated (p) SMAD1/5/8, the
      downstream molecules of Bmp signaling, during BUG epithelial development. These
      results suggest that Bmp signaling contributes to BUG development. Bmp receptor1a
      (Bmpr1a) is known as the major type 1 signal transducer in some organogeneses. To
      analyze the Bmp signaling function for BUG development, we examined epithelial
      cell-specific Bmpr1a gene conditional mutant mice utilizing the tamoxifen
      inducible Cre recombinase system. We observed cystic dilation and epithelial
      hyperplasia of the BUG in the Bmpr1a conditional knockout mice. The mutant cystic
      BUG specimens also showed inflammatory lesions. These BUG abnormalities resembled
      some of the BUG malformations observed in human congenital syndromes. The current
      study suggests that Bmp signaling possesses an essential role in BUG development
      and homeostasis. This would be the first report showing that the mutation of the
      Bmpr1a gene in the BUG epithelia phenocopied some abnormalities of human
      congenital syndromes affecting the BUG duct.

PMID- 21848995
TI  - Seeking gene candidates responsible for developmental origins of health and
      disease.
AB  - Human epidemiological evidence has led scientists to theorize that undernutrition
      during gestation is an important early origin of adult diseases. Animal models
      have successfully demonstrated that maternal diet could contribute to some adult
      diseases. Undernutrition is perceived harmful in pregnant women, whereas calorie
      restriction is a strategy proven to extend healthy and maximum lifespan in adult.
      This diagrammatically opposite effect of nutritional condition might provide us
      with hints to search for genes underlying health conditions. Here, we have
      initiated a study examining the effect of undernutrition on maternal and fetal
      livers, utilizing high-throughput DNA microarray analysis for screening genome
      wide changes in their transcriptomes. Briefly, pregnant mice were exposed to food
      deprivation (FD) on gestation day (GD) 17, and cesarean section was performed on
      GD18. Control mice were supplied with chow ad libitum until sacrifice. Total RNA
      extracted from mother and fetal livers for each control and treatment (FD) was
      analyzed with an Agilent mouse whole genome DNA chip. A total of 3058 and 3126 up
      (>1.5-fold) and down- (<0.75-fold) regulated genes, and 1475 and 1225 up- (>1.5
      fold) and down- (<0.75-fold) regulated genes showed differential expression at
      the mRNA level, in the maternal and fetal livers, respectively. Interestingly,
      103 genes up-regulated in the mother were down-regulated in the fetus, whereas
      108 down-regulated maternal genes were up-regulated in the fetus; these 211 genes
      are potential candidates related to longevity or health. The role of some of
      these genes, in context of the proposed mechanisms for developmental origins of
      health and disease is discussed.

PMID- 21848996
TI  - Association of drug treatments in pregnant women with the risk of external ear
      congenital abnormalities in their offspring: a population-based case-control
      study.
AB  - The objective of this study was to evaluate the possible association of drug
      treatments in pregnant women with a higher risk of congenital abnormalities of
      the external ear, particularly microtia/anotia, in their children. The frequency
      of drug treatments was compared in the mothers of cases with isolated or multiple
      (syndromic) ear abnormalities and in the mothers of three different controls:
      controls matched to cases, all controls (these controls had no defects) and
      malformed controls in the population-based large dataset of the Hungarian Case
      Control Surveillance of Congenital Abnormalities. There was no significantly
      higher use of any drug in the mothers of 354 cases with isolated external ear
      abnormalities than in the mothers of different controls. However, of 156 cases
      with multiple ear abnormalities, 11 had mothers with hydroxyethylrutosidea
      treatment and a characteristic pattern of congenital abnormalities was found in
      these children. Four cases with multiple ear abnormalities were born to epileptic
      mothers treated with valproate, phenytoin and polytherapy in two cases. Drug
      treatments are not important in the origin of isolated ear abnormalities.
      However, a higher risk of multiple ear abnormalities was found in children born
      to mothers with treatment of hydroxyethylrutosidea or antiepileptic drugs during
      pregnancy.

PMID- 21848997
TI  - Morphological and morphometric study on sphenoid and basioccipital ossification
      in normal human fetuses.
AB  - Congenital anomalies of the brain frequently correspond to cranial base
      anomalies, and a detailed description of morphology and individual variations in
      the developing cranial base is of clinical importance for diagnosing anomalies.
      Development of the human cranial base has been studied using dissection, computed
      tomography, and magnetic resonance imaging, each of which has advantages and
      disadvantages. We here examined development of the normal human fetal cranial
      base using bone staining, which allows for direct observation of the ossification
      centers and precise three-dimensional measurements. We observed alizarin red S
      stained sphenoids and basiocciputs of 22 normal formalin-fixed human fetuses with
      crown-rump lengths (CRL) of 115-175 mm. We defined landmarks and measured
      sphenoids and basiocciputs using a fine caliper. Growth patterns of these
      ossifying bones were obtained, and we found similarities and differences among
      the growth patterns. We also observed individual variations in the ossification
      patterns, in particular, single- or double-ossification center patterns for the
      basisphenoid. The orbitosphenoid and basisphenoid widths and ratios of the widths
      to the total cranial base width were significantly different between the two
      pattern groups, whereas the other measurements and their ratios to the total
      cranial base did not differ between the groups. We measured the cerebrum and pons
      in different sets of 22 human fetuses with CRLs of 105-186 mm and found close
      relationships with the development of corresponding parts of the cranial base.
      The results contribute to the quantitative and qualitative information about the
      growth patterns and variations during human fetal cranial base development.

PMID- 21848998
TI  - Differences in spontaneous fetal abnormalities among three outbred stocks of
      Wistar Hannover rats in Japan.
AB  - Wistar Hannover rats, which are maintained by three animal breeders in Japan,
      were examined to obtain basic data on reproductive and developmental parameters.
      Untreated pregnant females were terminated on gestational day 20, and the fetuses
      were removed by cesarian section. The fetuses were counted, weighed and examined
      for morphological abnormalities. There were few differences among the three
      stocks of Wistar Hannover rats on the numbers of implantations and live fetuses,
      sex ratio and fetal weights. The most common fetal abnormalities were the
      presence of left-sided umbilical arteries, supernumerary ribs and wavy ribs. The
      incidences of these abnormalities were different among the three stocks of Wistar
      Hannover rats. Our results provide important data which should be considered in
      the determination of which stock of rat is used in developmental studies.

PMID- 21848999
TI  - Gastroschisis with extracorporeal liver and stomach associated with
      sacrococcygeal teratoma and limb abnormalities.
AB  - Gastroschisis is the herniation of abdominal viscera through a paramedian
      abdominal wall fusion defect without involvement of the umbilical cord.
      Evisceration usually contains intestinal loops and has no surrounding membrane.
      Rarely, herniation of other major viscera such as stomach and liver occurs, which
      makes the prognosis worse. Gastroschisis is usually not associated with
      sacrococcygeal teratoma. In the present report, a very rare case of gastroschisis
      associated with sacrococcygeal teratoma is described. The gastroschisis had
      complete evisceration of the stomach, bowel and extracorporeal liver. A large
      sacrococcygeal mass was located on the posteroinferior part of the trunk and
      gluteal region, and was completely external. The fetus also showed a malrotated
      lower limb and talipes equinovarus.

PMID- 21849000
TI  - Effect of continuous positive airway pressure treatment on seizure control in
      patients with obstructive sleep apnea and epilepsy.
AB  - In patients with epilepsy, improvement in seizure control with treatment of
      coexisting obstructive sleep apnea (OSA) has been reported, but there is lack of
      data on the effect of continuous positive airway pressure (CPAP) compliance on
      seizure control in these patients. We examined the variability in seizure
      frequency in patients who were CPAP compliant and those who were not CPAP
      compliant. We undertook a retrospective review of clinical and polysomnographic
      data of adult patients with OSA and epilepsy seen at the Boston University
      Medical Center Epilepsy and Sleep Clinics between 2000 and 2010. Data were
      reviewed for CPAP compliance and seizure frequency after at least 6 months of
      CPAP use. Only patients with no changes in antiepileptic drug regimens during
      CPAP trial were included. Of the 660 patients identified, 41 fulfilled inclusion
      criteria, of whom 28 were CPAP compliant and 13 were not CPAP compliant. In the
      compliant group, CPAP use led to decreased seizure frequency from 1.8 per month
      to 1 per month (p = 0.01). In the noncompliant group, no significant difference
      in seizure frequency was noted between baseline (2.1 per month) and at follow-up
      (1.8 per month, p = 0.36). Sixteen of 28 CPAP-compliant subjects were seizure
      free, whereas only 3 of 13 non-CPAP compliant subjects were seizure free
      [relative risk (RR) 1.54, p = 0.05]. Patients with epilepsy and OSA not compliant
      with CPAP treatment are at higher risk of seizures than are CPAP-compliant
      patients. To validate this observation, further prospective studies are
      warranted.

PMID- 21849001
TI  - A life-threatening episode of treatment-resistant haemolysis in a pregnant
      patient with dyserythropoietic anaemia (CDA) type I.

PMID- 21849002
TI  - From CEMD to CEMACH to CMACE to...? Where now for the confidential enquiries into
      maternal deaths?

PMID- 21849003
TI  - The application of multiparameter reference intervals for pre-donation capillary
      blood counts: the experience of a single institution.
AB  - OBJECTIVES: To evaluate a set of reference counts applied to multiparameter pre
      counts in blood donors. AIM: Analyse the impact of pre-donation counts and
      specific reference intervals on donors' management. BACKGROUND: Multiparameter
      blood counts allow an improved enrollment process of blood donors due to a prompt
      identification of abnormalities involving haemoglobin (Hb), white blood cells
      (WBC) and platelets (PLT). METHODS/MATERIALS: Multiple pre-donation capillary
      counts were applied in the enrollment process of 13,347 consecutive donors. The
      rate of specific alterations of permanent exclusion and donor readmittance to
      donations for temporary exclusion had been evaluated, applying a set of
      multiparameter reference intervals. RESULTS: Alterations involved Hb in 72.55% of
      cases, mean corpuscular volume (MCV) in 20.99%, total WBC in 9.39%, lymphocytes
      in 7.55% and PLT in 6.07%. Among donors with initial alterations (543; 4.06%),
      12.70% were readmitted to donations within 15 days, 14.36% had permanent
      exclusion, 36.83% underwent prompt supplementation treatment and 36.09% were lost
      at follow-up or refused treatments. DISCUSSION: The systematic use of blood count
      reference intervals and pre-donation multiparameter blood counts allowed prompt
      identification of WBC, PLT and MCV alterations, readmittance within 15 days of
      12.70% of initially excluded donors and contributed to prompt management of
      supplement deficiency.

PMID- 21849005
TI  - What makes a good editorial?

PMID- 21849004
TI  - Adipose tissue and inflammation.

PMID- 21849006
TI  - Systematic reviews - a perspective on benefits and concerns in 2011. Safe, sound
      and sorted?

PMID- 21849007
TI  - Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin
      and metformin vs. pioglitazone in drug-naive patients with type 2 diabetes.
AB  - AIM: The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin
      (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and
      moderate-to-severe hyperglycaemia (A1C = 7.5-12.0%). METHODS: In an initial 12
      week phase (Phase A), 492 patients were randomised 1 : 1 in a double-blind
      fashion to SITA (100 mg qd) or PIO (15 mg qd, up-titrated to 30 mg after 6
      weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET
      (up-titrated to 50/1000 mg bid over 4 weeks) and the PIO group was up-titrated to
      45 mg qd RESULTS: At the end of Phase A, mean changes from baseline were -1.0%
      and -0.9% for A1C; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose; and 
      52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO,
      respectively. At the end of Phase B, improvements in glycaemic parameters were
      greater with SITA/MET vs. PIO: -1.7% vs. -1.4% for A1C (p = 0.002); -45.8 mg/dl
      vs. -37.6 mg/dl for fasting plasma glucose (p = 0.03); -90.3 mg/dl vs. -69.1
      mg/dl for 2-h postmeal glucose (p = 0.001); and 55.0% vs. 40.5% for patients with
      A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse
      events and a significantly lower incidence of oedema were observed with SITA/MET
      vs. PIO. The incidence of hypoglycaemia was similarly low in both groups. Body
      weight decreased with SITA/MET and increased with PIO (-1.1 kg vs. 3.4 kg; p <
      0.001). CONCLUSION: Improvements in glycaemic control were greater with SITA/MET
      vs. PIO, with weight loss vs. weight gain. Both treatments were generally well
      tolerated.

PMID- 21849008
TI  - Adipose tissue pro-inflammatory gene expression is associated with cardiovascular
      disease.
AB  - BACKGROUND: Obese patients are at high risk of developing cardiovascular disease.
      Several studies suggest obesity as an independent risk factor. Adipose tissue is
      now accepted as an endocrine organ that produces and secretes a variety of
      cytokines, hormones and other metabolic players involved in the pathogenesis of
      atherosclerosis. Among this versatile group of mediators and effectors of
      inflammation and atherothrombosis, we have studied the expression of matrix
      metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1),
      plasminogen activator inhibitor-1 (PAI-1), interleukin-18 (IL-18) and interleukin
      6 (IL-6). All these markers, in their circulatory form, have been associated with
      cardiovascular disease. However, there is no much data available on their
      expression in adipose tissue in human subjects with and without cardiovascular
      disease. MATERIAL AND METHODS: We successfully isolated RNA from subcutaneous fat
      biopsies of 61 patients with or without cardiovascular disease. We then measured
      the RNA expression of MMP-9, TIMP-1, PAI-1, IL-18 and IL-6 with Real-Time PCR,
      using relative quantification. RESULTS: Albeit not statistically significant, all
      inflammatory mediators - except IL-18 - were highly expressed in patients with
      cardiovascular disease (n = 16) compared with those without (n = 45). Pooling the
      gene expression data, trying to capture the overall inflammatory activity in
      adipose tissue in a score system, we observed a highly significant association
      with CVD. CONCLUSIONS: Trying to capture the overall inflammatory activity, in
      addition to the mass of adipose tissue, could provide useful hints towards a
      pathogenetic link between obesity and presence of cardiovascular disease.

PMID- 21849009
TI  - Medication discontinuation with depot and oral antipsychotics in outpatients with
      schizophrenia: comparison of matched cohorts from a 12-month observational study.
AB  - AIMS: This study compared all-cause medication discontinuation (any switch,
      augmentation or medication discontinuation) in matched cohorts of patients with
      schizophrenia who were initiated on depot or oral antipsychotics. Other
      objectives included between-group comparisons of resource use, and clinical and
      functional outcomes. METHODS: This post hoc analysis of a one-year, multicentre,
      prospective, observational study included outpatients with schizophrenia who
      required a change in their antipsychotic medication because of a physician
      perceived risk of medication non-adherence. Patients were matched 1 : 1 using an
      optimal algorithm with rank-based Mahalanobis distances. All-cause medication
      discontinuation was compared using the Klein and Moeschberger test for survival
      and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a
      Cox proportional hazards model, stratifying on matched pairs. RESULTS: Forty
      patients who initiated a depot antipsychotic could be matched to patients who
      initiated an oral antipsychotic. Fewer depot-treated patients discontinued their
      antipsychotic medication at least once compared with oral-treated patients [20%
      (8/40) vs. 40% (16/40)]. Depot-treated patients discontinued their medication
      later (Klein and Moeschberger test p = 0.025) and were less likely to discontinue
      their initial antipsychotic medication [HR = 0.33 (95% CI, 0.12-0.92), p = 0.033]
      than oral-treated patients. There were few differences in resource use and no
      differences in clinical and functional outcomes between cohorts. CONCLUSION: In
      this matched-cohort analysis, patients with schizophrenia who were considered to
      be non-adherent with their prior oral antipsychotics were less likely to
      discontinue their medication for any cause if they were initiated on depot
      compared with oral antipsychotics.

PMID- 21849010
TI  - Effectiveness of interventions to improve antidepressant medication adherence: a
      systematic review.
AB  - Non-adherence to antidepressant medications is a significant barrier to the
      successful treatment of depression in clinical practice. This review aims to
      systematically assess the effectiveness of interventions for improving
      antidepressant medication adherence among patients with unipolar depression, and
      to evaluate the effect of these interventions on depression clinical outcomes.
      MEDLINE, PsycINFO and EMBASE databases were searched for English-language
      randomised controlled trials published between January 1990 and December 2010 on
      interventions to improve antidepressant adherence. The impact of interventions on
      antidepressant medication adherence (compliance and persistence) and depression
      clinical outcomes was evaluated. Data concerning the quality of the included
      studies were also extracted. Twenty-six studies met the inclusion criteria.
      Interventions were classified as educational, behavioural and multifaceted
      interventions. A total of 28 interventions were tested, as two studies
      investigated two interventions each. Sixteen (57%) of the 28 interventions showed
      significant effects on antidepressant adherence outcomes, whereas 12 (43%)
      interventions demonstrated significant effects on both antidepressant adherence
      and depression outcomes. The interventions which showed significant improvement
      in outcomes were primarily multifaceted and complex, with proactive care
      management and involvement of mental health specialists. The most commonly used
      elements of multifaceted interventions included patient educational strategies,
      telephone follow-up to monitor patients' progress, as well as providing
      medication support and feedback to primary care providers. Overall, educational
      interventions alone were ineffective in improving antidepressant medication
      adherence. In conclusion, improving adherence to antidepressants requires a
      complex behavioural change and there is some evidence to support behavioural and
      multifaceted interventions as the most effective in improving antidepressant
      medication adherence and depression outcomes. More carefully designed and well
      conducted studies are needed to clarify the effect of interventions in different
      patient populations and treatment settings.

PMID- 21849011
TI  - Symptom change after discontinuation of successful antimuscarinic treatment in
      patients with overactive bladder symptoms: a randomised, multicentre trial.
AB  - AIMS: Efficacy of antimuscarinic therapy for overactive bladder (OAB) has been
      demonstrated; however, the durability of its effects is unknown. The study was
      conducted to evaluate symptom change and retreatment rate after discontinuation
      of antimuscarinic therapy. Also, we tried to find risk factors for retreatment.
      METHODS: This was a prospective, randomised, open-label, multicentre trial at
      four university hospitals. Women who had OAB symptoms for >= 6 months and who
      showed successful response to 1 month of Tolterodine 4 mg medication were
      randomly assigned to one of three groups: (A) discontinue medication, (B) 2-month
      additional medication and (C) 5-month additional medication. After completion of
      the 1-, 3- or 6-month treatment, patients stopped the medication and were
      followed up for additional 3 months to assess symptom relapse and retreatment
      rates. Risk factors for retreatment were evaluated. RESULTS: Of a total of 558
      patients who took the study medication, 173 were randomised and 108 (A: 40, B:
      40, C: 28) were included in the analysis. At the end of the treatment, the mean
      micturition frequency was decreased to 8.3/24 h from 11.7/24 h, and the mean
      urgency episode was decreased to 2.2/24 h from 8.0/24 h. Three months after
      discontinuation, the micturition frequency and the urgency episode were increased
      to 9.1/24 and 4.4/24 h respectively. Sixty five per cent of patients requested
      retreatment, and 62% experienced symptom relapse. Baseline health-related quality
      of life was the only independent risk factor for retreatment. DISCUSSION AND
      CONCLUSION: Discontinuation of antimuscarinic therapy resulted in high symptom
      relapse and retreatment rates regardless of treatment duration. The results
      provide new information on the durability of the efficacy of antimuscarinics, and
      may improve treatment efficacy by promoting the medication persistence of
      antimuscarinics in OAB patients.

PMID- 21849012
TI  - Behind intravenous iron therapy for heart failure: the downside?

PMID- 21849013
TI  - IV iron in heart failure: theoretical concerns need clinical confirmation.

PMID- 21849014
TI  - Rheumatic disease research and implications for clinical care, a comment.

PMID- 21849015
TI  - Transferring evidence from recent clinical rheumatology studies to those on the
      front lines.

PMID- 21849016
TI  - Dimension reduction with gene expression data using targeted variable importance
      measurement.
AB  - BACKGROUND: When a large number of candidate variables are present, a dimension
      reduction procedure is usually conducted to reduce the variable space before the
      subsequent analysis is carried out. The goal of dimension reduction is to find a
      list of candidate genes with a more operable length ideally including all the
      relevant genes. Leaving many uninformative genes in the analysis can lead to
      biased estimates and reduced power. Therefore, dimension reduction is often
      considered a necessary predecessor of the analysis because it can not only reduce
      the cost of handling numerous variables, but also has the potential to improve
      the performance of the downstream analysis algorithms. RESULTS: We propose a TMLE
      VIM dimension reduction procedure based on the variable importance measurement
      (VIM) in the frame work of targeted maximum likelihood estimation (TMLE). TMLE is
      an extension of maximum likelihood estimation targeting the parameter of
      interest. TMLE-VIM is a two-stage procedure. The first stage resorts to a machine
      learning algorithm, and the second step improves the first stage estimation with
      respect to the parameter of interest. CONCLUSIONS: We demonstrate with
      simulations and data analyses that our approach not only enjoys the prediction
      power of machine learning algorithms, but also accounts for the correlation
      structures among variables and therefore produces better variable rankings. When
      utilized in dimension reduction, TMLE-VIM can help to obtain the shortest
      possible list with the most truly associated variables.

PMID- 21849017
TI  - A comparison of the functional modules identified from time course and static PPI
      network data.
AB  - BACKGROUND: Cellular systems are highly dynamic and responsive to cues from the
      environment. Cellular function and response patterns to external stimuli are
      regulated by biological networks. A protein-protein interaction (PPI) network
      with static connectivity is dynamic in the sense that the nodes implement so
      called functional activities that evolve in time. The shift from static to
      dynamic network analysis is essential for further understanding of molecular
      systems. RESULTS: In this paper, Time Course Protein Interaction Networks (TC
      PINs) are reconstructed by incorporating time series gene expression into PPI
      networks. Then, a clustering algorithm is used to create functional modules from
      three kinds of networks: the TC-PINs, a static PPI network and a pseudorandom
      network. For the functional modules from the TC-PINs, repetitive modules and
      modules contained within bigger modules are removed. Finally, matching and GO
      enrichment analyses are performed to compare the functional modules detected from
      those networks. CONCLUSIONS: The comparative analyses show that the functional
      modules from the TC-PINs have much more significant biological meaning than those
      from static PPI networks. Moreover, it implies that many studies on static PPI
      networks can be done on the TC-PINs and accordingly, the experimental results are
      much more satisfactory. The 36 PPI networks corresponding to 36 time points,
      identified as part of this study, and other materials are available at
      http://bioinfo.csu.edu.cn/txw/TC-PINs.

PMID- 21849018
TI  - Integrated postdischarge transitional care in a hospitalist system to improve
      discharge outcome: an experimental study.
AB  - BACKGROUND: The postdischarge period is a vulnerable time for patients, with high
      rates of adverse events that may cause unnecessary readmissions, especially in
      the elderly. Because postdischarge care continuity is often interrupted after
      hospitalist care, close follow-up may decrease patient readmission. In this
      study, we aimed to investigate the impact of a quality improvement program,
      integrated postdischarge transitional care (PDTC), in Taiwan's hospitalist
      system. METHODS: From December 2009 to May 2010, patients admitted to the
      hospitalist ward of a medical center in Taiwan and later discharged alive to home
      care were included. Efforts to improve the quality of interventions in the PDTC
      program, including a disease-specific care plan, telephone monitoring, hotline
      counseling and referral to a hospitalist-run clinic, were implemented in the
      latter four months in the intervention group, while the control group was
      recruited during the first two months of the study period. The primary end point
      was unplanned readmission or death within 30 days after discharge. RESULTS: There
      were 94 and 219 patients in the control and intervention groups, respectively.
      Both groups had similar characteristics at the time of admission and at
      discharge. In the intervention group, 18 patients with worsening disease-specific
      indicators recorded during telephone monitoring and 21 patients with new or
      worsening symptoms recorded during hotline counseling had higher rates of
      unplanned readmission than those without worsening disease-specific indicators (P
      = 0.031) and worsening symptoms (P = 0.019), respectively. Patients who received
      PDTC had lower rates of readmission and death than the control group within 30
      days after discharge (15% vs. 25%; P = 0.021). Nonuse of a hospitalist-run clinic
      and presence of underlying malignancy were other independent risk factors for
      readmission and death within 30 days after discharge. CONCLUSION: Integrated PDTC
      using disease-specific care, telephone monitoring, hotline counseling and a
      hospitalist-run clinic can reduce rates of postdischarge readmission and death.

PMID- 21849019
TI  - LeukoCatch, a quick and efficient tool for the preparation of leukocyte extracts
      from blood.
AB  - BACKGROUND: Whole-protein extracts from peripheral blood leukocytes are ideal for
      basic and clinical research. However, lack of a simple preparation technique has
      limited the use of such extracts. The aim of this study is to develop a simple
      and easy system that can selectively obtain leukocyte extracts without
      hemoglobin. METHODS: A filter that captures the leukocytes but not RBCs was set
      at the bottom of a 10-mL medical syringe by sandwiching it between plastic
      stoppers. The capturing efficiency of leukocytes with this tool, called
      LeukoCatch, was examined using human macrophage cells (MONO-MAC-6). The abilities
      of LeukoCatch system to capture the leukocyte proteins and to remove the
      hemoglobin from RBCs were tested by western blot analysis using human blood
      samples. RESULTS: This study presents the development of LeukoCatch, a novel tool
      that allows the preparation of leukocyte extracts from blood samples within 3 min
      without centrifugation. Tissue-cultured human macrophage cells were tested to
      determine the optimal filter numbers and pass-through frequencies of LeukoCatch,
      which was then applied to 2-mL blood samples. Samples were passed 2~5 times
      through a LeukoCatch equipped with 5 filters, washed twice with phosphate
      buffered saline for red cell removal, and leukocyte proteins were extracted with
      0.5 mL of elution buffer. Western blot analysis of the purified extract indicated
      that more than 90% of hemoglobin was removed by the LeukoCatch and that the
      protein recovery rate of leukocytes was at least 4 times better than that of the
      conventional centrifugation method. CONCLUSION: We conclude that LeukoCatch is
      useful not only for diagnosis at the bedside but also for basic research using
      blood samples or tissue culture cells.

PMID- 21849020
TI  - The effect of perceived discrimination on the health of immigrant workers in
      Spain.
AB  - BACKGROUND: Discrimination is an important determinant of health inequalities,
      and immigrants may be more vulnerable to certain types of discrimination than the
      native-born. This study analyses the relationship between immigrants' perceived
      discrimination and various self-reported health indicators. METHODS: A cross
      sectional survey was conducted (2008) amongst a non-random sample of 2434
      immigrants from Ecuador, Morocco, Romania and Colombia in four Spanish cities:
      Barcelona, Huelva, Madrid and Valencia. A factorial analysis of variables
      revealed three dimensions of perceived discrimination (due to immigrant status,
      due to physical appearance, and workplace-related). The association of these
      dimensions with self-rated health, mental health (GHQ-12), change in self-rated
      health between origin and host country, and other self-reported health outcomes
      was analysed. Logistic regression was used adjusting for potential confounders
      (aOR-95%CI). Subjects with worsening self-reported health status potentially
      attributable to perceived discrimination was estimated (population attributable
      proportion, PAP %). RESULTS: 73.3% of men and 69.3% of women immigrants reported
      discrimination due to immigrant status. Moroccans showed the highest prevalence
      of perceived discrimination. Immigrants reporting discrimination were at
      significantly higher risk of reporting health problems than those not reporting
      discrimination. Workplace-related discrimination was associated with poor mental
      health (aOR 2.97 95%CI 2.45-3.60), and the worsening of self-rated health (aOR
      2.20 95%CI 1.73- 2.80). 40% (95% CI 24-53) PAP of those reporting worse self
      rated health could be attributable to discrimination due to immigrant status.
      CONCLUSIONS: Discrimination may constitute a risk factor for health in immigrant
      workers in Spain and could explain some health inequalities among immigrant
      populations in Spanish society.

PMID- 21849021
TI  - The muscle satellite cell at 50: the formative years.
AB  - In February 1961, Alexander Mauro described a cell 'wedged' between the plasma
      membrane of the muscle fibre and the surrounding basement membrane. He postulated
      that it could be a dormant myoblast, poised to repair muscle when needed. In the
      same month, Bernard Katz also reported a cell in a similar location on muscle
      spindles, suggesting that it was associated with development and growth of
      intrafusal muscle fibres. Both Mauro and Katz used the term 'satellite cell' in
      relation to their discoveries. Today, the muscle satellite cell is widely
      accepted as the resident stem cell of skeletal muscle, supplying myoblasts for
      growth, homeostasis and repair.Since 2011 marks both the 50th anniversary of the
      discovery of the satellite cell, and the launch of Skeletal Muscle, it seems an
      opportune moment to summarise the seminal events in the history of research into
      muscle regeneration. We start with the 19th-century pioneers who showed that
      muscle had a regenerative capacity, through to the descriptions from the mid-20th
      century of the underlying cellular mechanisms. The journey of the satellite cell
      from electron microscope curio, to its gradual acceptance as a bona fide myoblast
      precursor, is then charted: work that provided the foundations for our
      understanding of the role of the satellite cell. Finally, the rapid progress in
      the age of molecular biology is briefly discussed, and some ongoing debates on
      satellite cell function highlighted.

PMID- 21849022
TI  - Knockdown of Rab5a expression decreases cancer cell motility and invasion through
      integrin-mediated signaling pathway.
AB  - BACKGROUND: Rab GTPases function as modulators in intracellular transport. Rab5a,
      a member of the Rab subfamily of small GTPases, is an important regulator of
      vesicle traffic from the plasma membrane to early endosomes. Recent findings have
      reported that Rab5a gene was involved in the progression of cancer. In the
      present study, we investigated the effect of Rab5a on cervical cancer invasion
      and metastasis and the molecular mechanism underlying the involvement of Rab5a.
      METHODS: Rab5a expression was assessed by immunohistochemical analysis on a
      cervical cancer tissue microarray. RNA interference (RNAi) was performed to knock
      down the endogenous expression of Rab5a gene in HeLa and SiHa cells. Cell
      motility was evaluated using invasion assay and wound migration assay in vitro.
      The expression levels of integrin-associated molecules were detected by Western
      blot and immunofluorescence. RESULTS: We found that Rab5a was expressed at a high
      level in cervical cancer tissues. Silencing of Rab5a expression significantly
      decreased cancer cell motility and invasiveness. The down-regulation of integrin
      associated focal adhesion signaling molecules was further detected in Rab5a
      knockdown cells. Meanwhile, active GTP-bound Rac1, Cdc42, and RhoA were also down
      regulated, accompanied with the reduction in the number and size of filopodia and
      lamellipodia. CONCLUSIONS: Taken together, these data suggest that Rab5a
      functions in regulating the invasion phenotype, and we propose that this
      regulation may be via integrin-mediated signaling pathway in cervical cancer
      cells.

PMID- 21849023
TI  - No association of TNFRSF1B variants with type 2 diabetes in Indians of Indo
      European origin.
AB  - BACKGROUND: There has been no systematic evaluation of the association between
      genetic variants of type 2 receptor for TNFalpha (TNFR2) and type 2 diabetes,
      despite strong biological evidence for the role of this receptor in the
      pathogenesis of this complex disorder. In view of this, we performed a
      comprehensive association analysis of TNFRSF1B variants with type 2 diabetes in
      4,200 Indo-European subjects from North India. METHODS: The initial phase
      evaluated association of seven SNPs viz. rs652625, rs496888, rs6697733, rs945439,
      rs235249, rs17883432 and rs17884213 with type 2 diabetes in 2,115 participants
      (1,073 type 2 diabetes patients and 1,042 control subjects). Further, we
      conducted replication analysis of three associated SNPs in 2,085 subjects (1,047
      type 2 diabetes patients and 1,038 control subjects). RESULTS: We observed
      nominal association of rs945439, rs235249 and rs17884213 with type 2 diabetes (P
      < 0.05) in the initial phase. Haplotype CC of rs945439 and rs235249 conferred
      increased susceptibility for type 2 diabetes [OR = 1.19 (95%CI 1.03-1.37), P =
      0.019/Pperm = 0.076] whereas, TG haplotype of rs235249 and rs17884213 provided
      protection against type 2 diabetes [OR = 0.83 (95%CI 0.72-0.95, P = 7.2 * 10
      3/Pperm = 0.019]. We also observed suggestive association of rs496888 with plasma
      hsCRP levels [P = 0.042]. However, the association of rs945439, rs235249 and
      rs17884213 with type 2 diabetes was not replicated in the second study
      population. Meta-analysis of the two studies also failed to detect any
      association with type 2 diabetes. CONCLUSIONS: Our two-stage association analysis
      suggests that TNFRSF1B variants are not the determinants of genetic risk of type
      2 diabetes in North Indians.

PMID- 21849024
TI  - Illness management and recovery (IMR) in Danish community mental health centres.
AB  - BACKGROUND: Schizophrenia and bipolar disorder are severe mental illnesses that
      can have a significant disabling impact on the lives of people. Psychosocial
      interventions that stress hope and recovery as a part of a multi-dimensional
      approach are possibly indicated to support people with severe mental illness in
      facilitating recovery. Illness Management and Recovery (IMR) is a curriculum
      based psychosocial intervention designed as structured program with a recovery
      oriented approach. The aim of IMR is to rehabilitate people with severe mental
      illnesses by helping them acquire knowledge and skills in managing their illness
      and achieve personal recovery goals. Previous randomised clinical trials indicate
      that IMR can be implemented with a good effect and a high fidelity though further
      trials are crucial to demonstrate the potential effectiveness of IMR.
      METHODS/DESIGN: The trial design is a randomised, assessor-blinded, multi-centre,
      clinical trial of the IMR program compared with treatment as usual for 200
      participants diagnosed with schizophrenia or bipolar disorder under the care of
      two community mental health centres in the Capital Region of Denmark. The primary
      outcome is level of functioning at the end of treatment. The secondary outcomes
      are disease symptoms; use of alcohol/drugs; individual meaning of recovery; hope;
      hospital admissions and out-patient psychiatric treatment at the end of treatment
      and the abovementioned and level of functioning at follow-up 21 months after
      baseline. DISCUSSION: If the results of this trial show IMR to be effective these
      positive results will strengthen the evidence of IMR as an effective
      comprehensive psychosocial intervention with a recovery-oriented approach for
      people with severe mental illness. This will have significant implications for
      the treatment and recovery of people with severe mental illness.

PMID- 21849025
TI  - Functional characterization of cellulases identified from the cow rumen fungus
      Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses.
AB  - BACKGROUND: Neocallimastix patriciarum is one of the common anaerobic fungi in
      the digestive tracts of ruminants that can actively digest cellulosic materials,
      and its cellulases have great potential for hydrolyzing cellulosic feedstocks.
      Due to the difficulty in culture and lack of a genome database, it is not easy to
      gain a global understanding of the glycosyl hydrolases (GHs) produced by this
      anaerobic fungus. RESULTS: We have developed an efficient platform that uses a
      combination of transcriptomic and proteomic approaches to N. patriciarum to
      accelerate gene identification, enzyme classification and application in rice
      straw degradation. By conducting complementary studies of transcriptome (Roche
      454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219
      putative GH contigs and classified them into 25 GH families. The secretome
      analysis identified four major enzymes involved in rice straw degradation: beta
      glucosidase, endo-1,4-beta-xylanase, xylanase B and Cel48A exoglucanase. From the
      sequences of assembled contigs, we cloned 19 putative cellulase genes, including
      the GH1, GH3, GH5, GH6, GH9, GH18, GH43 and GH48 gene families, which were highly
      expressed in N. patriciarum cultures grown on different feedstocks. CONCLUSIONS:
      These GH genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae
      for functional characterization. At least five novel cellulases displayed
      cellulytic activity for glucose production. One beta-glucosidase (W5-16143) and
      one exocellulase (W5-CAT26) showed strong activities and could potentially be
      developed into commercial enzymes.

PMID- 21849026
TI  - Does weight loss improve semen quality and reproductive hormones? Results from a
      cohort of severely obese men.
AB  - BACKGROUND: A high body mass index (BMI) has been associated with reduced semen
      quality and male subfecundity, but no studies following obese men losing weight
      have yet been published. We examined semen quality and reproductive hormones
      among morbidly obese men and studied if weight loss improved the reproductive
      indicators. METHODS: In this pilot cohort study, 43 men with BMI > 33 kg/m2 were
      followed through a 14 week residential weight loss program. The participants
      provided semen samples and had blood samples drawn, filled in questionnaires, and
      had clinical examinations before and after the intervention. Conventional semen
      characteristics as well as sperm DNA integrity, analysed by the sperm chromatin
      structure assay (SCSA) were obtained. Serum levels of testosterone, estradiol,
      sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle
      stimulating hormone (FSH), anti-Mullerian hormone (AMH) and inhibin B (Inh-B)
      were measured. RESULTS: Participants were from 20 to 59 years of age (median =
      32) with BMI ranging from 33 to 61 kg/m2. At baseline, after adjustment for
      potential confounders, BMI was inversely associated with sperm concentration (p =
      0.02), total sperm count (p = 0.02), sperm morphology (p = 0.04), and motile
      sperm (p = 0.005) as well as testosterone (p = 0.04) and Inh-B (p = 0.04) and
      positively associated to estradiol (p < 0.005). The median (range) percentage
      weight loss after the intervention was 15% (3.5-25.4). Weight loss was associated
      with an increase in total sperm count (p = 0.02), semen volume (p = 0.04),
      testosterone (p = 0.02), SHBG (p = 0.03) and AMH (p = 0.02). The group with the
      largest weight loss had a statistically significant increase in total sperm count
      [193 millions (95% CI: 45; 341)] and normal sperm morphology [4% (95% CI: 1; 7)].
      CONCLUSION: This study found obesity to be associated with poor semen quality and
      altered reproductive hormonal profile. Weight loss may potentially lead to
      improvement in semen quality. Whether the improvement is a result of the
      reduction in body weight per se or improved lifestyles remains unknown.

PMID- 21849027
TI  - Alcohol-related brief intervention in patients treated for opiate or cocaine
      dependence: a randomized controlled study.
AB  - BACKGROUND: Despite the importance of heavy drinking and alcohol dependence among
      patients with opiate and cocaine dependence, few studies have evaluated specific
      interventions within this group. The aim of the present study was to evaluate the
      impact of screening with the Alcohol Use Disorders Identification Test (AUDIT)
      and of brief intervention (BI) on alcohol use in a sample of patients treated for
      opioid or cocaine dependence in a specialized outpatient clinic. METHODS: Adult
      outpatients treated for opioid or cocaine dependence in Switzerland were screened
      for excessive alcohol drinking and dependence with the AUDIT. Patients with AUDIT
      scores that indicated excessive drinking or dependence were randomized into two
      groups--treatment as usual or treatment as usual together with BI--and assessed
      at 3 months and 9 months. RESULTS: Findings revealed a high rate (44%) of
      problematic alcohol use (excessive drinking and dependence) among patients with
      opiate and cocaine dependence. The number of drinks per week decreased
      significantly between T0 (inclusion) and T3 (month 3). A decrease in average
      AUDIT scores was observed between T0 and T3 and between T0 and T9 (month 9). No
      statistically significant difference between treatment groups was observed.
      CONCLUSIONS: In a substance abuse specialized setting, screening for alcohol use
      with the AUDIT, followed by feedback on the score, and use of alcohol BI are both
      possibly useful strategies to induce changes in problematic alcohol use.
      Definitive conclusions cannot, however, be drawn from the study because of
      limitations such as lack of a naturalistic group. An important result of the
      study is the excellent internal consistency of AUDIT in a population treated for
      opiate or cocaine dependence.

PMID- 21849029
TI  - "No God and no Norway": collective resource loss among members of Tamil NGO's in
      Norway during and after the last phase of the civil war in Sri Lanka.
AB  - BACKGROUND: Studies on the mental health of refugees have tended to focus upon
      the impact of traumatic experiences in the country of origin, and acculturation
      processes in exile. The effects of crises in the country of origin on refugees
      living in exile have been little studied. This article examines how the final
      stages of the civil war in Sri Lanka in 2009 influenced members of pro-LTTE Tamil
      NGO's in Norway. METHOD: Ethnographic fieldwork methods were employed within
      Tamil NGO's in the two largest cities in Norway between November 2008 and June
      2011. RESULTS: The findings suggest that collective resources became severely
      drained as a result of the crisis, severely disrupting the fabric of social life.
      Public support from the majority community remained scarce throughout the crisis.
      CONCLUSIONS: The study suggests that there is a need for public support to exile
      groups indirectly affected by man-made crises in their country of origin.

PMID- 21849028
TI  - Do infants fed directly from the breast have improved appetite regulation and
      slower growth during early childhood compared with infants fed from a bottle?
AB  - BACKGROUND: Behavioral mechanisms that contribute to the association between
      breastfeeding and reduced obesity risk are poorly understood. The purpose of this
      study was to evaluate the hypothesis that feeding human milk from the breast
      (direct breastfeeding) has a more optimal association with subsequent child
      appetite regulation behaviors and growth, when compared to bottle-feeding.
      METHODS: Children (n = 109) aged 3- to 6- years were retrospectively classified
      as directly breastfed (fed exclusively at the breast), bottle-fed human milk, or
      bottle-fed formula in the first three months of life. Young children's appetite
      regulation was examined by measuring three constructs (satiety response, food
      responsiveness, enjoyment of food) associated with obesity risk, using the Child
      Eating Behavior Questionnaire. Multinomial logistic regression analyses were used
      to test whether children bottle-fed either human milk or formula had reduced odds
      of high satiety and increased odds of high food responsiveness and high enjoyment
      of food compared to children fed directly from the breast. Current child weight
      status and growth trends from 6-36 months were also examined for their relation
      to direct breastfeeding and appetite regulation behaviors in early childhood.
      RESULTS: Children fed human milk in a bottle were 67% less likely to have high
      satiety responsiveness compared to directly breastfed children, after controlling
      for child age, child weight status, maternal race/ethnicity, and maternal
      education. There was no association of bottle-feeding (either human milk or
      formula) with young children's food responsiveness and enjoyment of food. There
      was neither an association of direct breastfeeding with current child weight
      status, nor was there a clear difference between directly breastfed and bottle
      fed children in growth trajectories from 6- to 36-months. More rapid infant
      changes in weight-for-age score were associated with lower satiety
      responsiveness, higher food responsiveness and higher enjoyment of food in later
      childhood CONCLUSION: While direct breastfeeding was not found to differentially
      affect growth trajectories from infancy to childhood compared to bottle-feeding,
      results suggest direct breastfeeding during early infancy is associated with
      greater appetite regulation later in childhood. A better understanding of such
      behavioral distinctions between direct breastfeeding and bottle-feeding may
      identify new pathways to reduce the pediatric obesity epidemic.

PMID- 21849030
TI  - Anamnestic risk factor questionnaire as reliable diagnostic instrument for
      osteoporosis (reduced bone morphogenic density).
AB  - BACKGROUND: Osteoporosis is a major health problem worldwide, and is included in
      the WHO list of the top 10 major diseases. However, it is often undiagnosed until
      the first fracture occurs, due to inadequate patient education and lack of
      insurance coverage for screening tests. Anamnestic risk factors like positive
      family anamnesis or early menopause are assumed to correlate with reduced BMD.
      METHODS: In our study of 78 patients with metaphyseal long bone fractures, we
      searched for a correlation between anamnestic risk factors, bone specific
      laboratory values, and the bone morphogenic density (BMD). Each indicator was
      examined as a possible diagnostic instrument for osteoporosis. The secondary aim
      of this study was to demonstrate the high prevalence of osteoporosis in patients
      with metaphyseal fractures. RESULTS: 76.9% of our fracture patients had decreased
      bone density and 43.6% showed manifest osteoporosis in DXA (densitometry)
      measurements. Our questionnaire, identifying anamnestic risk factors, correlated
      highly significantly (p = 0.01) with reduced BMD, whereas seven bone-specific
      laboratory values (p = 0.046) correlated significantly. CONCLUSIONS: Anamnestic
      risk factors correlate with pathological BMD. The medical questionnaire used in
      this study would therefore function as a cost-effective primary diagnostic
      instrument for identification of osteoporosis patients.

PMID- 21849031
TI  - Regional and temporal variations in coding of hospital diagnoses referring to
      upper gastrointestinal and oesophageal bleeding in Germany.
AB  - BACKGROUND: Health insurance claims data are increasingly used for health
      services research in Germany. Hospital diagnoses in these data are coded
      according to the International Classification of Diseases, German modification
      (ICD-10-GM). Due to the historical division into West and East Germany, different
      coding practices might persist in both former parts. Additionally, the
      introduction of Diagnosis Related Groups (DRGs) in Germany in 2003/2004 might
      have changed the coding. The aim of this study was to investigate regional and
      temporal variations in coding of hospitalisation diagnoses in Germany. METHODS:
      We analysed hospitalisation diagnoses for oesophageal bleeding (OB) and upper
      gastrointestinal bleeding (UGIB) from the official German Hospital Statistics
      provided by the Federal Statistical Office. Bleeding diagnoses were classified as
      "specific" (origin of bleeding provided) or "unspecific" (origin of bleeding not
      provided) coding. We studied regional (former East versus West Germany)
      differences in incidence of hospitalisations with specific or unspecific coding
      for OB and UGIB and temporal variations between 2000 and 2005. For each year,
      incidence ratios of hospitalisations for former East versus West Germany were
      estimated with log-linear regression models adjusting for age, gender and
      population density. RESULTS: Significant differences in specific and unspecific
      coding between East and West Germany and over time were found for both, OB and
      UGIB hospitalisation diagnoses, respectively. For example in 2002, incidence
      ratios of hospitalisations for East versus West Germany were 1.24 (95% CI 1.16
      1.32) for specific and 0.67 (95% CI 0.60-0.74) for unspecific OB diagnoses and
      1.43 (95% CI 1.36-1.51) for specific and 0.83 (95% CI 0.80-0.87) for unspecific
      UGIB. Regional differences nearly disappeared and time trends were less marked
      when using combined specific and unspecific diagnoses of OB or UGIB,
      respectively. CONCLUSIONS: During the study period, there were substantial
      regional and temporal variations in the coding of OB and UGIB diagnoses in
      hospitalised patients. Possible explanations for the observed regional variations
      are different coding preferences, further influenced by changes in coding and
      reimbursement rules. Analysing groups of diagnoses including specific and
      unspecific codes reduces the influence of varying coding practices.

PMID- 21849032
TI  - Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double
      heterozygosity.
AB  - BACKGROUND: Both epidemiological and experimental studies suggest that
      heterozygosity for a single gene is linked with tumorigenesis and heterozygosity
      for two genes increases the risk of tumor incidence. Our previous work has
      demonstrated that Atm/Brca1 double heterozygosity leads to higher cell
      transformation rate than single heterozygosity. However, the underlying
      mechanisms have not been fully understood yet. In the present study, a series of
      pathways were investigated to clarify the possible mechanisms of increased risk
      of tumorigenesis in Atm and Brca1 heterozygosity. METHODS: Wild type cells, Atm
      or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were
      used to investigate DNA damage and repair, cell cycle, micronuclei, and cell
      transformation after photon irradiation. RESULTS: Remarkable high transformation
      frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild
      type cells. It was observed that delayed DNA damage recognition, disturbed cell
      cycle checkpoint, incomplete DNA repair, and increased genomic instability were
      involved in the biological networks. Haploinsufficiency of either ATM or BRCA1
      negatively impacts these pathways. CONCLUSIONS: The quantity of critical proteins
      such as ATM and BRCA1 plays an important role in determination of the fate of
      cells exposed to ionizing radiation and double heterozygosity increases the risk
      of tumorigenesis. These findings also benefit understanding of the individual
      susceptibility to tumor initiation.

PMID- 21849033
TI  - Long-term follow-up and treatment of congenital alveolar proteinosis.
AB  - BACKGROUND: Clinical presentation, diagnosis, management and outcome of
      molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to
      mutations in the GM-CSF receptor are not well known. CASE PRESENTATION: A 2 1/2
      years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages
      were performed with a new catheter balloon technique, feasible in small sized
      airways. Because of some interstitial inflammation in the lung biopsy and to
      further improve the condition, empirical therapy with systemic steroids and
      azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical
      measures, total protein and lipid recovered by whole lung lavages, all these
      treatments were without benefit. Conversely, severe respiratory viral infections
      and an invasive aspergillosis with aspergilloma formation occurred. Recently the
      novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was
      identified in the patient. This mutation leads to a lack of functional GMCSF
      receptor and a reduced response to GMCSF stimulation of CD11b expression of
      mononuclear cells of the patient. Subsequently a very intense treatment with
      monthly lavages was initiated, resulting for the first time in complete
      resolution of partial respiratory insufficiency and a significant improvement of
      the overall somato-psychosocial condition of the child. CONCLUSIONS: The long
      term management from early childhood into young adolescence of severe alveolar
      proteinosis due to GMCSF receptor deficiency requires a dedicated specialized
      team to perform technically demanding whole lung lavages and cope with
      complications.

PMID- 21849035
TI  - Extracting quantitative genetic interaction phenotypes from matrix combinatorial
      RNAi.
AB  - BACKGROUND: Systematic measurement of genetic interactions by combinatorial RNAi
      (co-RNAi) is a powerful tool for mapping functional modules and discovering
      components. It also provides insights into the role of epistasis on the way from
      genotype to phenotype. The interpretation of co-RNAi data requires computational
      and statistical analysis in order to detect interactions reliably and
      sensitively. RESULTS: We present a comprehensive approach to the analysis of
      univariate phenotype measurements, such as cell growth. The method is based on a
      quantitative model and is demonstrated on two example Drosophila cell culture
      data sets. We discuss adjustments for technical variability, data quality
      assessment, model parameter fitting and fit diagnostics, choice of scale, and
      assessment of statistical significance. CONCLUSIONS: As a result, we obtain
      quantitative genetic interactions and interaction networks reflecting known
      biological relationships between target genes. The reliable extraction of
      presence, absence, and strength of interactions provides insights into molecular
      mechanisms.

PMID- 21849036
TI  - Effectiveness and legitimacy of forest carbon standards in the OTC voluntary
      carbon market.
AB  - BACKGROUND: In recent years, the voluntary over-the-counter (OTC) carbon market
      has reached a significant market volume. It is particularly interesting for
      forest mitigation projects which are either ineligible in compliance markets or
      confronted with a plethora of technical and financial hurdles and lacking market
      demand. As the OTC market is not regulated, voluntary standards have been created
      to secure the social and environmental integrity of the traded mitigation
      projects and thus to ensure the quality of the resulting carbon credits. Building
      on a theoretical efficiency-legitimacy framework, this study aims to identify and
      analyse the characteristics and indicators that determine the efficiency and
      organisational legitimacy of standards for afforestation/reforestation carbon
      projects. RESULTS: All interviewed market actors consider third-party
      certification and standards as a crucial component of market functionality, which
      provide quality assurance mechanisms that reduce information asymmetries and
      moral hazard between the actors regarding the quality of carbon credits, and thus
      reduce transaction costs. Despite this development, the recent evolution of many
      new and differing standards is seen as a major obstacle that renders it difficult
      for project developers and buyers to select an appropriate standard. According to
      the interviewed experts the most important legitimating factors of standards are
      assurance of a sufficient level of quality of carbon credits, scientifically
      substantiated methodological accounting and independent third-party verification,
      independence of standard bodies, transparency, wide market acceptance, back-up of
      the wider community including experts and NGOs, rigorous procedures, and the
      resemblance to the Afforestation/Reforestation (A/R) CDM due to its international
      policy endorsements. In addition, standards must provide evidence that projects
      contribute to a positive social and environmental development, do no harm as a
      minimum requirement and build a strong track record of successful projects.
      Project developers require clear, easily and practically applicable standards at
      lowest possible costs with a high potential in order to achieve good carbon
      prices, while buyers require that standards are legitimate, credible and that no
      public criticism arises when carbon credits are purchased from projects certified
      by a certain standard. CONCLUSIONS: Despite the fragmented and immature state of
      the OTC market, standards act as 'market-making' intermediaries and contribute to
      the quality and transparency of the OTC market. However, the variety of different
      standards imposes new hurdles for their efficiency and often creates confusion
      instead of confidence among potential buyers. Despite the lacking legitimacy of
      the standards, pressures from the institutional environment on standards ensure a
      minimum quality of carbon credits (including positive social and environmental
      impacts of carbon credits) that serves as an insurance mechanism for the
      integrity of standards. Its unregulated nature and the pressure from an
      increasingly competitive environment provides innovative space to deliver
      efficient certification procedures without imposing unreasonably high transaction
      costs on market actors. Furthermore, voluntary standards imply a more innovative
      certification approach, as one legal authority could do, because standards have
      to compete for adopters backed by civil society organisations. Thereby, the
      forest sector in OTC voluntary market bears great opportunities to provide the
      forest sector with crucial lessons for international climate policy and
      governmental institutions when designing regulation for forest regulation such as
      international and national REDDplus schemes.

PMID- 21849034
TI  - Transport genes and chemotaxis in Laribacter hongkongensis: a genome-wide
      analysis.
AB  - BACKGROUND: Laribacter hongkongensis is a Gram-negative, sea gull-shaped rod
      associated with community-acquired gastroenteritis. The bacterium has been found
      in diverse freshwater environments including fish, frogs and drinking water
      reservoirs. Using the complete genome sequence data of L. hongkongensis, we
      performed a comprehensive analysis of putative transport-related genes and genes
      related to chemotaxis, motility and quorum sensing, which may help the bacterium
      adapt to the changing environments and combat harmful substances. RESULTS: A
      genome-wide analysis using Transport Classification Database TCDB, similarity and
      keyword searches revealed the presence of a large diversity of transporters (n =
      457) and genes related to chemotaxis (n = 52) and flagellar biosynthesis (n = 40)
      in the L. hongkongensis genome. The transporters included those from all seven
      major transporter categories, which may allow the uptake of essential nutrients
      or ions, and extrusion of metabolic end products and hazardous substances. L.
      hongkongensis is unique among closely related members of Neisseriaceae family in
      possessing higher number of proteins related to transport of ammonium, urea and
      dicarboxylate, which may reflect the importance of nitrogen and dicarboxylate
      metabolism in this assacharolytic bacterium. Structural modeling of two C4
      dicarboxylate transporters showed that they possessed similar structures to the
      determined structures of other DctP-TRAP transporters, with one having an unusual
      disulfide bond. Diverse mechanisms for iron transport, including hemin
      transporters for iron acquisition from host proteins, were also identified. In
      addition to the chemotaxis and flagella-related genes, the L. hongkongensis
      genome also contained two copies of qseB/qseC homologues of the AI-3 quorum
      sensing system. CONCLUSIONS: The large number of diverse transporters and genes
      involved in chemotaxis, motility and quorum sensing suggested that the bacterium
      may utilize a complex system to adapt to different environments. Structural
      modeling will provide useful insights on the transporters in L. hongkongensis.

PMID- 21849037
TI  - Change in antihypertensive drug prescribing after guideline implementation: a
      controlled before and after study.
AB  - BACKGROUND: Antihypertensive drug choices and treatment levels are not in
      accordance with the existing guidelines. We aimed to assess the impact of a
      guideline implementation intervention on antihypertensive drug prescribing.
      METHODS: In this controlled before and after study, the effects of a multifaceted
      (education, audit and feedback, local care pathway) quality programme was
      evaluated. The intervention was carried out in a health centre between 2002 and
      2003. From each health care unit (n = 31), a doctor-nurse pair was trained to act
      as peer facilitators in the intervention.All antihypertensive drugs prescribed by
      25 facilitator general practitioners (intervention GPs) and 53 control GPs were
      retrieved from the nationwide Prescription Register for three-month periods in
      2001 and 2003. The proportions of patients receiving specific antihypertensive
      drugs and multiple antihypertensive drugs were measured before and after the
      intervention for three subgroups of hypertension patients: hypertension only,
      with coronary heart disease, and with diabetes. RESULTS: In all subgroups, the
      use of multiple concurrent medications increased. For intervention patients with
      hypertension only, the odds ratio (OR) was 1.12 (95% CI 0.99, 1.25; p = 0.06) and
      for controls 1.13 (1.05, 1.21; p = 0.002). We observed no statistically
      significant differences in the change in the prescribing of specific
      antihypertensive agents between the intervention and control groups. The use of
      agents acting on the renin-angiotensin-aldosterone system increased in all
      subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p =
      0.004) and controls OR 1.24 (1.15, 1.34; p < 0.0001). CONCLUSIONS: A multifaceted
      guideline implementation intervention does not necessarily lead to significant
      changes in prescribing performance. Rigorous planning of the interventions and
      quality projects and their evaluation are essential.

PMID- 21849038
TI  - Impact of clostridial glucosylating toxins on the proteome of colonic cells
      determined by isotope-coded protein labeling and LC-MALDI.
AB  - BACKGROUND: The anaerobe Clostridium difficile produces two major virulence
      factors toxin A and B that inactivate Rho proteins by glucosylation of a pivotal
      threonine residue. Purified toxins induce reorganization of the cytoskeleton and
      cell death in colonic cells. Whether all toxin effects on target cells depend on
      catalytic glucosyltransferase activity is unclear at present. Thus, we conducted
      a proteome approach to compare the protein profile of target cells treated either
      with wild type toxin A (rTcdA wt) or with a catalytically inactive mutant toxin A
      (mutant rTcdA). Relative protein quantification was feasible using isotope-coded
      protein labeling techniques (ICPL) and mass spectrometry (LC-MALDI). RESULTS:
      Altogether we found a significant differential expression of thirty proteins
      after treatment with rTcdA wt or mutant rTcdA. Mutant rTcdA caused up-regulation
      of seven proteins and sixteen proteins were responsive to rTcdA wt after 5 h.
      Long-term effect of rTcdA wt on protein expression was the down-regulation of
      eleven proteins. Up- or down-regulation of several proteins was verified by
      western blot analysis confirming the MS results. CONCLUSION: Our results indicate
      incubation time-dependent effects of the clostridial glucosylating toxin A on
      colonic cells. The rTcdA wt impact more cellular functions than actin
      cytoskeleton reorganization and apoptosis. Furthermore, these data give insight
      into glucosyltransferase independent effects of clostridial glucosylating toxins
      on target cells after short incubation time. Additionally, our data reveal pro
      inflammatory and proliferative effects of mutant rTcdA after short-term
      incubation.

PMID- 21849040
TI  - Self-reported adverse reactions in 4337 healthcare workers immunizations against
      novel H1N1 influenza.
AB  - PURPOSE: The use of the 2009 H1N1 vaccine has generated much debate concerning
      safety issues among the general population and physicians. It was questioned if
      this is a safe vaccine. Therefore, we investigated the safety of an inactivated
      monovalent H1N1 pandemic influenza vaccine METHODS: We focused on the H1N1
      pandemic influenza vaccine Pandemrix(r) and applied a self reporting
      questionnaire in a population of healthcare workers (HCWs) and medical students
      at a major university hospital. RESULTS: In total, 4337 individuals were
      vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination
      rate of the employees was higher than 40%. The majority of individuals were
      vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported
      to lead to one or more adverse reactions (6.7%). Local reactions were reported in
      3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%.
      CONCLUSIONS: Our data together with available data from several national and
      international institutions points to a safe pandemic influenza vaccine.

PMID- 21849039
TI  - Lung function and organ dysfunctions in 178 patients requiring mechanical
      ventilation during the 2009 influenza A (H1N1) pandemic.
AB  - INTRODUCTION: Most cases of the 2009 influenza A (H1N1) infection are self
      limited, but occasionally the disease evolves to a severe condition needing
      hospitalization. Here we describe the evolution of the respiratory compromise,
      ventilatory management and laboratory variables of patients with diffuse viral
      pneumonitis caused by pandemic 2009 influenza A (H1N1) admitted to the ICU.
      METHOD: This was a multicenter, prospective inception cohort study including
      adult patients with acute respiratory failure requiring mechanical ventilation
      (MV) admitted to 20 ICUs in Argentina between June and September of 2009 during
      the influenza A (H1N1) pandemic. In a standard case-report form, we collected
      epidemiological characteristics, results of real-time reverse-transcriptase-
      polymerase-chain-reaction viral diagnostic tests, oxygenation variables, acid
      base status, respiratory mechanics, ventilation management and laboratory tests.
      Variables were recorded on ICU admission and at days 3, 7 and 10. RESULTS: During
      the study period 178 patients with diffuse viral pneumonitis requiring MV were
      admitted. They were 44 +/- 15 years of age, with Acute Physiology And Chronic
      Health Evaluation II (APACHE II) scores of 18 +/- 7, and most frequent
      comorbidities were obesity (26%), previous respiratory disease (24%) and
      immunosuppression (16%). Non-invasive ventilation (NIV) was applied in 49 (28%)
      patients on admission, but 94% were later intubated.Acute respiratory distress
      syndrome (ARDS) was present throughout the entire ICU stay in the whole group
      (mean PaO2/FIO2 170 +/- 25). Tidal-volumes used were 7.8 to 8.1 ml/kg (ideal body
      weight), plateau pressures always remained < 30 cmH2O, without differences
      between survivors and non-survivors; and mean positive end-expiratory pressure
      (PEEP) levels used were between 8 to 12 cm H2O. Rescue therapies, like
      recruitment maneuvers (8 to 35%), prone positioning (12 to 24%) and tracheal gas
      insufflation (3%) were frequently applied. At all time points, pH, platelet
      count, lactate dehydrogenase assay (LDH) and Sequential Organ Failure Assessment
      (SOFA) differed significantly between survivors and non-survivors. Lack of
      recovery of platelet count and persistence of leukocytosis were characteristic of
      non-survivors. Mortality was high (46%); and length of MV was 10 (6 to 17) days.
      CONCLUSIONS: These patients had severe, hypoxemic respiratory failure compatible
      with ARDS that persisted over time, frequently requiring rescue therapies to
      support oxygenation. NIV use is not warranted, given its high failure rate. Death
      and evolution to prolonged mechanical ventilation were common outcomes.
      Persistence of thrombocytopenia, acidosis and leukocytosis, and high LDH levels
      found in non-survivors during the course of the disease might be novel prognostic
      findings.

PMID- 21849041
TI  - Quality-of-life evaluation for advanced non-small-cell lung cancer: a comparison
      between vinorelbine plus gemcitabine followed by docetaxel versus paclitaxel plus
      carboplatin regimens in a randomized trial: Japan Multinational Trial
      Organization LC00-03 (BRI LC03-01).
AB  - BACKGROUND: A randomized trial of vinorelbine plus gemcitabine followed by
      docetaxel (VGD) versus paclitaxel plus carboplatin (PC) in patients with advanced
      non-small-cell lung cancer showed no difference in overall survival (median
      survival time: 13.6 versus 14.1 months) between the two treatment groups. We
      report here the results of quality-of-life (QOL) study initiated in the mid
      course of this randomized trial. METHODS: The patients themselves assessed the
      Functional Assessment of Cancer Therapy (FACT)-Lung (FACT-L), FACT-Taxane and the
      Functional Assessment of Chronic Illness Therapy - Spirituality (FACIT-Sp) QOL
      instruments at baseline and 6, 12 and 18 weeks after the treatment. The primary
      endpoint was a comparison of total QOL score for each assessment instrument
      between the two groups. RESULTS: Sixty-eight patients from the trial (VGD, 34;
      PC, 34) who submitted baseline questionnaires and at least one questionnaire over
      the course of treatment were eligible. Longitudinal analysis showed a significant
      difference in slope of the FACT-Taxane score (p = 0.004) between treatment
      regimens over time, but no difference was found in FACT-L score (p = 0.311) and
      FACIT-Sp score (p = 0.466) between the two groups. CONCLUSIONS: The significant
      difference in slope of FACT-Taxane score favored the VGD regimen. These data
      should be considered in treatment decision-making for patients with advanced non
      small-cell lung cancer. TRIAL REGISTRATION: NCT00242983.

PMID- 21849042
TI  - A systems approach to identifying correlated gene targets for the loss of colour
      pigmentation in plants.
AB  - BACKGROUND: The numerous diverse metabolic pathways by which plant compounds can
      be produced make it difficult to predict how colour pigmentation is lost for
      different tissues and plants. This study employs mathematical and in silico
      methods to identify correlated gene targets for the loss of colour pigmentation
      in plants from a whole cell perspective based on the full metabolic network of
      Arabidopsis. This involves extracting a self-contained flavonoid subnetwork from
      the AraCyc database and calculating feasible metabolic routes or elementary modes
      (EMs) for it. Those EMs leading to anthocyanin compounds are taken to constitute
      the anthocyanin biosynthetic pathway (ABP) and their interplay with the rest of
      the EMs is used to study the minimal cut sets (MCSs), which are different
      combinations of reactions to block for eliminating colour pigmentation. By
      relating the reactions to their corresponding genes, the MCSs are used to explore
      the phenotypic roles of the ABP genes, their relevance to the ABP and the impact
      their eliminations would have on other processes in the cell. RESULTS: Simulation
      and prediction results of the effect of different MCSs for eliminating colour
      pigmentation correspond with existing experimental observations. Two examples
      are: i) two MCSs which require the simultaneous suppression of genes DFR and ANS
      to eliminate colour pigmentation, correspond to observational results of the same
      genes being co-regulated for eliminating floral pigmentation in Aquilegia and;
      ii) the impact of another MCS requiring CHS suppression, corresponds to findings
      where the suppression of the early gene CHS eliminated nearly all flavonoids but
      did not affect the production of volatile benzenoids responsible for floral
      scent. CONCLUSIONS: From the various MCSs identified for eliminating colour
      pigmentation, several correlate to existing experimental observations, indicating
      that different MCSs are suitable for different plants, different cells, and
      different conditions and could also be related to regulatory genes. Being able to
      correlate the predictions with experimental results gives credence to the use of
      these mathematical and in silico analyses methods in the design of experiments.
      The methods could be used to prioritize target enzymes for different objectives
      to achieve desired outcomes, especially for less understood pathways.

PMID- 21849043
TI  - Data mining methods in the prediction of Dementia: A real-data comparison of the
      accuracy, sensitivity and specificity of linear discriminant analysis, logistic
      regression, neural networks, support vector machines, classification trees and
      random forests.
AB  - BACKGROUND: Dementia and cognitive impairment associated with aging are a major
      medical and social concern. Neuropsychological testing is a key element in the
      diagnostic procedures of Mild Cognitive Impairment (MCI), but has presently a
      limited value in the prediction of progression to dementia. We advance the
      hypothesis that newer statistical classification methods derived from data mining
      and machine learning methods like Neural Networks, Support Vector Machines and
      Random Forests can improve accuracy, sensitivity and specificity of predictions
      obtained from neuropsychological testing. Seven non parametric classifiers
      derived from data mining methods (Multilayer Perceptrons Neural Networks, Radial
      Basis Function Neural Networks, Support Vector Machines, CART, CHAID and QUEST
      Classification Trees and Random Forests) were compared to three traditional
      classifiers (Linear Discriminant Analysis, Quadratic Discriminant Analysis and
      Logistic Regression) in terms of overall classification accuracy, specificity,
      sensitivity, Area under the ROC curve and Press'Q. Model predictors were 10
      neuropsychological tests currently used in the diagnosis of dementia. Statistical
      distributions of classification parameters obtained from a 5-fold cross
      validation were compared using the Friedman's nonparametric test. RESULTS: Press'
      Q test showed that all classifiers performed better than chance alone (p < 0.05).
      Support Vector Machines showed the larger overall classification accuracy (Median
      (Me) = 0.76) an area under the ROC (Me = 0.90). However this method showed high
      specificity (Me = 1.0) but low sensitivity (Me = 0.3). Random Forest ranked
      second in overall accuracy (Me = 0.73) with high area under the ROC (Me = 0.73)
      specificity (Me = 0.73) and sensitivity (Me = 0.64). Linear Discriminant Analysis
      also showed acceptable overall accuracy (Me = 0.66), with acceptable area under
      the ROC (Me = 0.72) specificity (Me = 0.66) and sensitivity (Me = 0.64). The
      remaining classifiers showed overall classification accuracy above a median value
      of 0.63, but for most sensitivity was around or even lower than a median value of
      0.5. CONCLUSIONS: When taking into account sensitivity, specificity and overall
      classification accuracy Random Forests and Linear Discriminant analysis rank
      first among all the classifiers tested in prediction of dementia using several
      neuropsychological tests. These methods may be used to improve accuracy,
      sensitivity and specificity of Dementia predictions from neuropsychological
      testing.

PMID- 21849044
TI  - Autologous bone marrow stem cell intralesional transplantation repairing
      bisphosphonate related osteonecrosis of the jaw.
AB  - PURPOSE: Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well
      known side effect of bisphosphonate therapies in oncologic and non oncologic
      patients. Since to date no definitive consensus has been reached on the treatment
      of BRONJ, novel strategies for the prevention, risk reduction and treatment need
      to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to
      alendronate and pamidronate treatment of osteoporosis. The patient was
      unresponsive to recommended treatment of the disease, and her BRONJ was
      worsening. Since bone marrow stem cells are know as being multipotent and exhibit
      the potential for differentiation into different cells/tissue lineages, including
      cartilage, bone and other tissue, we performed autologous bone marrow stem cell
      transplantation into the BRONJ lesion of the patient. METHODS: Under local
      anesthesia a volume of 75 ml of bone marrow were harvested from the posterior
      superior iliac crest by aspiration into heparinized siringes. The cell suspension
      was concentrated, using Ficoll - Hypaque(r) centrifugation procedures, in a final
      volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the
      patient underwent surgical toilet, local anesthesia was done and spongostan was
      applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of
      stem cells suspension and 1 ml of patient's activated platelet-rich plasma were
      injected in the lesion of BRONJ. RESULTS: A week later the residual spongostan
      was removed and two weeks later resolution of symptoms was obtained. Then the
      lesion improved with progressive superficialization of the mucosal layer and CT
      scan, performed 15 months later, shows improvement also of bone via concentric
      ossification: so complete healing of BRONJ (stage 0) was obtained in our patient,
      and 30 months later the patient is well and without signs of BRONJ. CONCLUSION:
      To our knowledge this is the first case of BRONJ successfully treated with
      autologous stem cells transplantation with a complete response.

PMID- 21849045
TI  - Understanding the 'four directions of travel': qualitative research into the
      factors affecting recruitment and retention of doctors in rural Vietnam.
AB  - BACKGROUND: Motivation and retention of health workers, particularly in rural
      areas, is a question of considerable interest to policy-makers internationally.
      Many countries, including Vietnam, are debating the right mix of interventions to
      motivate doctors in particular to work in remote areas. The objective of this
      study was to understand the dynamics of the health labour market in Vietnam, and
      what might encourage doctors to accept posts and remain in-post in rural areas.
      METHODS: This study forms part of a labour market survey which was conducted in
      Vietnam in November 2009 to February 2010. The study had three stages. This
      article describes the findings of the first stage - the qualitative research and
      literature review, which fed into the design of a structured survey (second
      stage) and contingent valuation (third stage). For the qualitative research,
      three tools were used - key informant interviews at national and provincial level
      (6 respondents); in-depth interviews of doctors at district and commune levels
      (11 respondents); and focus group discussions with medical students (15
      participants). RESULTS: The study reports on the perception of the problem by
      national level stakeholders; the motivation for joining the profession by
      doctors; their views on the different factors affecting their willingness to work
      in rural areas (including different income streams, working conditions, workload,
      equipment, support and supervision, relationships with colleagues, career
      development, training, and living conditions). It presents findings on their
      overall satisfaction, their ranking of different attributes, and willingness to
      accept different kinds of work. Finally, it discusses recent and possible policy
      interventions to address the distribution problem. CONCLUSIONS: Four typical
      'directions of travel' are identified for Vietnamese doctors - from lower to
      higher levels of the system, from rural to urban areas, from preventive to
      curative health and from public to private practice. Substantial differences in
      income from formal and informal sources all reinforce these preferences. While
      non-financial attributes are also important for Vietnamese doctors, the scale of
      the difference of opportunities presents a considerable policy challenge.
      Significant salary increases for doctors in hard-to-staff areas are likely to
      have some impact. However, addressing the differentials is likely to require
      broader market reforms and regulatory measures.

PMID- 21849046
TI  - Non-invasive markers for hepatic fibrosis.
AB  - With great advancements in the therapeutic modalities used for the treatment of
      chronic liver diseases, the accurate assessment of liver fibrosis is a vital need
      for successful individualized management of disease activity in patients. The
      lack of accurate, reproducible and easily applied methods for fibrosis assessment
      has been the major limitation in both the clinical management and for research in
      liver diseases. However, the problem of the development of biomarkers capable of
      non-invasive staging of fibrosis in the liver is difficult due to the fact that
      the process of fibrogenesis is a component of the normal healing response to
      injury, invasion by pathogens, and many other etiologic factors. Current non
      invasive methods range from serum biomarker assays to advanced imaging techniques
      such as transient elastography and magnetic resonance imaging (MRI). Among non
      invasive methods that gain strongest clinical foothold are FibroScan elastometry
      and serum-based APRI and FibroTest. There are many other tests that are not yet
      widely validated, but are none the less, promising. The rate of adoption of non
      invasive diagnostic tests for liver fibrosis differs from country to country, but
      remains limited. At the present time, use of non-invasive procedures could be
      recommended as pre-screening that may allow physicians to narrow down the
      patients' population before definitive testing of liver fibrosis by biopsy of the
      liver. This review provides a systematic overview of these techniques, as well as
      both direct and indirect biomarkers based approaches used to stage fibrosis and
      covers recent developments in this rapidly advancing area.

PMID- 21849047
TI  - A novel method to compare protein structures using local descriptors.
AB  - BACKGROUND: Protein structure comparison is one of the most widely performed
      tasks in bioinformatics. However, currently used methods have problems with the
      so-called "difficult similarities", including considerable shifts and distortions
      of structure, sequential swaps and circular permutations. There is a demand for
      efficient and automated systems capable of overcoming these difficulties, which
      may lead to the discovery of previously unknown structural relationships.
      RESULTS: We present a novel method for protein structure comparison based on the
      formalism of local descriptors of protein structure - DEscriptor Defined
      Alignment (DEDAL). Local similarities identified by pairs of similar descriptors
      are extended into global structural alignments. We demonstrate the method's
      capability by aligning structures in difficult benchmark sets: curated alignments
      in the SISYPHUS database, as well as SISY and RIPC sets, including non-sequential
      and non-rigid-body alignments. On the most difficult RIPC set of sequence
      alignment pairs the method achieves an accuracy of 77% (the second best method
      tested achieves 60% accuracy). CONCLUSIONS: DEDAL is fast enough to be used in
      whole proteome applications, and by lowering the threshold of detectable
      structure similarity it may shed additional light on molecular evolution
      processes. It is well suited to improving automatic classification of structure
      domains, helping analyze protein fold space, or to improving protein
      classification schemes. DEDAL is available online at
      http://bioexploratorium.pl/EP/DEDAL.

PMID- 21849048
TI  - Concurrent sexual partnerships and associated factors: a cross-sectional
      population-based survey in a rural community in Africa with a generalised HIV
      epidemic.
AB  - BACKGROUND: Although concurrent sexual partnerships may play an important role in
      HIV transmission in Africa, the lack of an agreed definition of concurrency and
      of standard methodological approaches has hindered studies. In a long-standing
      general population cohort in rural Uganda we assessed the prevalence of
      concurrency and investigated its association with sociodemographic and
      behavioural factors and with HIV prevalence, using the new recommended standard
      definition and methodological approaches. METHODS: As part of the 2010 annual
      cohort HIV serosurvey among adults, we used a structured questionnaire to collect
      information on sociodemographic and behavioural factors and to measure standard
      indicators of concurrency using the recommended method of obtaining sexual
      partner histories. We used logistic regression to build a multivariable model of
      factors independently associated with concurrency. RESULTS: Among those eligible,
      3,291 (66%) males and 4,052 (72%) females participated in the survey. Among
      currently married participants, 11% of men and 25% of women reported being in a
      polygynous union. Among those with a sexual partner in the past year, the
      proportion reporting at least one concurrent partnership was 17% in males and
      0.5% in females. Polygyny accounted for a third of concurrency in men and was not
      associated with increased HIV risk. Among men there was no evidence of an
      association between concurrency and HIV prevalence (but too few women reported
      concurrency to assess this after adjusting for confounding). Regarding
      sociodemographic factors associated with concurrency, females were significantly
      more likely to be younger, unmarried, and of lower socioeconomic status than
      males. Behavioural factors associated with concurrency were young age at first
      sex, increasing lifetime partners, and a casual partner in the past year (among
      men and women) and problem drinking (only men). CONCLUSIONS: Our findings based
      on the new standard definition and methodological approaches provide a baseline
      for measuring changes in concurrency and HIV incidence in future surveys, and a
      benchmark for other studies. As campaigns are now widely conducted against
      concurrency, such surveys and studies are important in evaluating their
      effectiveness in decreasing HIV transmission.

PMID- 21849049
TI  - BLProt: prediction of bioluminescent proteins based on support vector machine and
      relieff feature selection.
AB  - BACKGROUND: Bioluminescence is a process in which light is emitted by a living
      organism. Most creatures that emit light are sea creatures, but some insects,
      plants, fungi etc, also emit light. The biotechnological application of
      bioluminescence has become routine and is considered essential for many medical
      and general technological advances. Identification of bioluminescent proteins is
      more challenging due to their poor similarity in sequence. So far, no specific
      method has been reported to identify bioluminescent proteins from primary
      sequence. RESULTS: In this paper, we propose a novel predictive method that uses
      a Support Vector Machine (SVM) and physicochemical properties to predict
      bioluminescent proteins. BLProt was trained using a dataset consisting of 300
      bioluminescent proteins and 300 non-bioluminescent proteins, and evaluated by an
      independent set of 141 bioluminescent proteins and 18202 non-bioluminescent
      proteins. To identify the most prominent features, we carried out feature
      selection with three different filter approaches, ReliefF, infogain, and mRMR. We
      selected five different feature subsets by decreasing the number of features, and
      the performance of each feature subset was evaluated. CONCLUSION: BLProt achieves
      80% accuracy from training (5 fold cross-validations) and 80.06% accuracy from
      testing. The performance of BLProt was compared with BLAST and HMM. High
      prediction accuracy and successful prediction of hypothetical proteins suggests
      that BLProt can be a useful approach to identify bioluminescent proteins from
      sequence information, irrespective of their sequence similarity. The BLProt
      software is available at http://www.inb.uni-luebeck.de/tools
      demos/bioluminescent%20protein/BLProt.

PMID- 21849050
TI  - Downregulation of TFPI in breast cancer cells induces tyrosine phosphorylation
      signaling and increases metastatic growth by stimulating cell motility.
AB  - BACKGROUND: Increased hemostatic activity is common in many cancer types and
      often causes additional complications and even death. Circumstantial evidence
      suggests that tissue factor pathway inhibitor-1 (TFPI) plays a role in cancer
      development. We recently reported that downregulation of TFPI inhibited apoptosis
      in a breast cancer cell line. In this study, we investigated the effects of TFPI
      on self-sustained growth and motility of these cells, and of another invasive
      breast cancer cell type (MDA-MB-231). METHODS: Stable cell lines with TFPI (both
      alpha and beta) and only TFPIbeta downregulated were created using RNA
      interference technology. We investigated the ability of the transduced cells to
      grow, when seeded at low densities, and to form colonies, along with metastatic
      characteristics such as adhesion, migration and invasion. RESULTS: Downregulation
      of TFPI was associated with increased self-sustained cell growth. An increase in
      cell attachment and spreading was observed to collagen type I, together with
      elevated levels of integrin alpha2. Downregulation of TFPI also stimulated
      migration and invasion of cells, and elevated MMP activity was involved in the
      increased invasion observed. Surprisingly, equivalent results were observed when
      TFPIbeta was downregulated, revealing a novel function of this isoform in cancer
      metastasis. CONCLUSIONS: Our results suggest an anti-metastatic effect of TFPI
      and may provide a novel therapeutic approach in cancer.

PMID- 21849051
TI  - Evaluation of Abelmoschus moschatus extracts for antioxidant, free radical
      scavenging, antimicrobial and antiproliferative activities using in vitro assays.
AB  - BACKGROUND: Abelmoschus moschatus Medik. leaves and seeds are considered as
      valuable traditional medicine. The aromatic seeds of this plant are aphrodisiac,
      ophthalmic, cardio tonic, antispasmodic and used in the treatment of intestinal
      complaints and check queasiness. To give a scientific basis for traditional usage
      of this medicinal plant, the seed and leaf extracts were evaluated for their
      antioxidant, free radical scavenging, antimicrobial and antiproliferative
      activities. METHODS: In this study, antioxidant, antimicrobial and
      antiproliferative activities of A. moschatus extracts were evaluated in a series
      of in vitro assay involving free radicals, reactive oxygen species and their IC50
      values were also determined. The antioxidant activities of the seed and leaf
      extracts of A. moschatus were determined by total antioxidant, DPPH, and ferrous
      reducing antioxidant property (FRAP) methods. In addition, the antiproliferative
      activity was also evaluated using colorectal adenocarcinoma and retinoblastoma
      human cancer cell lines. Moreover, six bacterial reference strains, two gram
      positive (Bacillus subtilis and Staphylococcus aureus), four gram-negative
      (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Salmonella
      enterica paratyphi) and one fungal strain (Candida albicans) were used to
      evaluate its antimicrobial activity. RESULTS: The results from this study showed
      that the antioxidant activities of A. moschatus as determined by the total
      phenol, flavonoids, total antioxidant and FRAP methods were higher in leaf than
      that of the seed extracts. On the other hand, the aqueous overnight seed extract
      (AMS-I) has shown significant radical scavenging activity as in 1, 1- Diphenyl-2
      picrylhydrazyl (DPPH), hydrogen peroxide, hydroxyl radical, superoxide and lipid
      peroxidation as compared to other seed and leaf extracts. The AMS-I and AML-IV
      have shown activity against six and seven microorganisms respectively.
      Simulteneously, AMS-IV and AML-IV have demonstrated potential antiproliferative
      activity against two human cell lines - Colorectal adenocarcinoma (COLO-205) and
      retinoblastoma (Y79). CONCLUSION: The seed and leaf extracts of A. moschatus
      possess significant antioxidant activity and could serve as free radical
      inhibitors or scavenger, or substitute, probably as primary antioxidants. The
      plant possesses moderate antibacterial activity against bacterial strains used in
      this study. Hydroalcoholic seed and leaf extracts also exhibited
      antiproliferative activity against two human cancer cell lines. A. moschatus may
      therefore, be a good candidate for functional foods as well as pharmaceutics.

PMID- 21849052
TI  - Comparison of pharmacist managed anticoagulation with usual medical care in a
      family medicine clinic.
AB  - BACKGROUND: The beneficial outcomes of oral anticoagulation therapy are dependent
      upon achieving and maintaining an optimal INR therapeutic range. There is growing
      evidence that better outcomes are achieved when anticoagulation is managed by a
      pharmacist with expertise in anticoagulation management rather than usual care by
      family physicians. This study compared a pharmacist managed anticoagulation
      program (PC) to usual physician care (UC) in a family medicine clinic. METHODS: A
      retrospective cohort study was carried out in a family medicine clinic which
      included a clinical pharmacist. In 2006, the pharmacist assumed anticoagulation
      management. For a 17-month period, the PC group (n = 112) of patients on warfarin
      were compared to the UC patients (n = 81) for a similar period prior to 2006. The
      primary outcome was the percentage of time patients' INR was in the therapeutic
      range (TTR). Secondary outcomes were the percentage of time in therapeutic range
      within +/- 0.3 units of the recommended range (expanded TTR) and percentage of
      time the INR was >5.0 or <1.5. RESULTS: The baseline characteristics were similar
      between the groups. Fifty-five percent of the PC group was male with a mean age
      of 67 years; 51% of the UC group was male with a mean age of 71 years. The most
      common indications for warfarin in both groups were atrial fibrillation,
      mechanical heart valves and deep vein thrombosis. The TTR was 73% for PC and 65%
      for UC (p < 0.0001). The expanded TTR for PC was 91% and 85% for UC (p < 0.0001).
      The percentage of time INR values were <1.5 was 0.7% for PC patients and 1.9% for
      UC patients (p < 0.0001), and >5 were 0.3% for PC patients and 0.1% for UC (p <
      0.0001). CONCLUSION: The pharmacist-managed anticoagulation program within a
      family practice clinic compared to usual care by the physicians achieved
      significantly better INR control as measured by the percentage of time patients'
      INR values were kept in both the therapeutic and expanded range. Based on the
      results of this study, a collaborative family practice clinic using pharmacists
      and physicians may be an effective model for anticoagulation management with
      these results verified in future prospective randomized studies.

PMID- 21849053
TI  - Use of Maximum Likelihood-Mixed Models to select stable reference genes: a case
      of heat stress response in sheep.
AB  - BACKGROUND: Reference genes with stable expression are required to normalize
      expression differences of target genes in qPCR experiments. Several procedures
      and companion software have been proposed to find the most stable genes. Model
      based procedures are attractive because they provide a solid statistical
      framework. NormFinder, a widely used software, uses a model based method. The
      pairwise comparison procedure implemented in GeNorm is a simpler procedure but
      one of the most extensively used. In the present work a statistical approach
      based in Maximum Likelihood estimation under mixed models was tested and compared
      with NormFinder and geNorm softwares. Sixteen candidate genes were tested in
      whole blood samples from control and heat stressed sheep. RESULTS: A model
      including gene and treatment as fixed effects, sample (animal), gene by
      treatment, gene by sample and treatment by sample interactions as random effects
      with heteroskedastic residual variance in gene by treatment levels was selected
      using goodness of fit and predictive ability criteria among a variety of models.
      Mean Square Error obtained under the selected model was used as indicator of gene
      expression stability. Genes top and bottom ranked by the three approaches were
      similar; however, notable differences for the best pair of genes selected for
      each method and the remaining genes of the rankings were shown. Differences among
      the expression values of normalized targets for each statistical approach were
      also found. CONCLUSIONS: Optimal statistical properties of Maximum Likelihood
      estimation joined to mixed model flexibility allow for more accurate estimation
      of expression stability of genes under many different situations. Accurate
      selection of reference genes has a direct impact over the normalized expression
      values of a given target gene. This may be critical when the aim of the study is
      to compare expression rate differences among samples under different
      environmental conditions, tissues, cell types or genotypes. To select reference
      genes not only statistical but also functional and biological criteria should be
      considered. Under the method here proposed SDHA/MDH1 have arisen as the best set
      of reference genes to be used in qPCR assays to study heat shock in ovine blood
      samples.

PMID- 21849054
TI  - Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy
      versus supportive psychotherapy for early onset chronic depression: design and
      rationale of a multisite randomized controlled trial.
AB  - BACKGROUND: Effective treatment strategies for chronic depression are urgently
      needed since it is not only a common and particularly disabling disorder, but is
      also considered treatment resistant by most clinicians. There are only a few
      studies on chronic depression indicating that traditional psycho- and
      pharmacological interventions are not as effective as in acute, episodic
      depression. Current medications are no more effective than those introduced 50
      years ago whereas the only psychotherapy developed specifically for the subgroup
      of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy
      (CBASP), faired well in one large trial. However, CBASP has never been directly
      compared to a non-specific control treatment. METHODS/DESIGN: The present article
      describes the study protocol of a multisite parallel-group randomized controlled
      trial in Germany. The purpose of the study is to estimate the efficacy of CBASP
      compared to supportive psychotherapy in 268 non-medicated early-onset chronically
      depressed outpatients. The intervention includes 20 weeks of acute treatment with
      24 individual sessions followed by 28 weeks of continuation treatment with
      another 8 sessions. Depressive symptoms are evaluated 20 weeks after
      randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD).
      Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission
      after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of
      covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of
      continuous secondary variables will be performed using linear mixed models. For
      remission rates, chi-squared tests and logistic regression will be applied.
      DISCUSSION: The study evaluates the comparative effects of a disorder-specific
      psychotherapy and a well designed non-specific psychological approach in the
      acute and continuation treatment phase in a large sample of early-onset
      chronically depressed patients. TRIAL REGISTRATION: ClinicalTrials.gov
      (NCT00970437).

PMID- 21849055
TI  - Taping patients with clinical signs of subacromial impingement syndrome: the
      design of a randomized controlled trial.
AB  - BACKGROUND: Shoulder problems are a common complaint of the musculoskeletal
      system. Physical therapists treat these patients with different modalities such
      as exercise, massage, and shoulder taping. Although different techniques have
      been described, the effectiveness of taping has not yet been established. The aim
      of this study is to assess the effectiveness and cost-effectiveness of usual
      physical therapy care in combination with a particular tape technique for
      subacromial impingement syndrome of the shoulder compared to usual physical
      therapy care without this tape technique in a primary healthcare setting. METHODS
      AND DESIGN: An economic evaluation alongside a randomized controlled trial will
      be conducted. A sample of 140 patients between 18 and 65 years of age with a
      diagnosis of subacromial impingement syndrome (SAIS) as assessed by physical
      therapists will be recruited. Eligible patients will be randomized to either the
      intervention group (usual care in combination with the particular tape technique)
      or the control group (usual care without this tape technique). In both groups,
      usual care will consist of individualized physical therapy care. The primary
      outcomes will be shoulder-specific function (the Simple Shoulder Test) and pain
      severity (11-point numerical rating scale). The economic evaluation will be
      performed using a societal perspective. All relevant costs will be registered
      using cost diaries. Utilities (Quality Adjusted Life Years) will be measured
      using the EuroQol. The data will be collected at baseline, and 4, 12, and 26
      weeks follow-up. DISCUSSION: This pragmatic study will provide information about
      the effectiveness and cost-effectiveness of taping in patients presenting with
      clinical signs of SAIS. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: NTR2575.

PMID- 21849057
TI  - Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an
      underrecognized disease with poor outcome.
AB  - BACKGROUND: Non-nosocomial healthcare-associated infective endocarditis (NNHCA
      IE) is a new category of IE of increasing importance. This study described the
      clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan.
      METHODS: A retrospective study was conducted of all patients with IE admitted to
      the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year
      period from July 2004 to July 2009. The clinical and microbiological features of
      NNHCA-IE were compared to those of community-acquired and nosocomial IE.
      Predictors for in-hospital death were determined. RESULTS: Two-hundred episodes
      of confirmed IE occurred during the study period. These included 148 (74%)
      community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%)
      nosocomial healthcare-associated IE. Staphylococcus aureus was the most frequent
      pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older
      (median age, 67 vs. 44, years, p < 0.001), had more MRSA (43.3% vs. 9.5%, p <
      0.001), more comorbidity conditions (median Charlson comorbidity index
      [interquartile range], 4[2-6] vs. 0[0-1], p < 0.001), a higher in-hospital
      mortality (50.0% vs. 17.6%, p < 0.001) and were less frequently recognized by
      clinicians on admission (16.7% vs. 47.7%, p = 0.002). The overall in-hospital
      mortality rate for all patients with IE was 25%. Shock was the strongest risk
      factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, p
      < 0.001). CONCLUSIONS: NNHCA-IE is underrecognized and carries a high mortality
      rate. Early recognition is crucial to provide optimal management and improve
      outcome.

PMID- 21849056
TI  - Resveratrol suppresses human colon cancer cell proliferation and induces
      apoptosis via targeting the pentose phosphate and the talin-FAK signaling
      pathways-A proteomic approach.
AB  - BACKGROUND: We and others have previously reported that resveratrol (RSV)
      suppresses colon cancer cell proliferation and elevates apoptosis in vitro and/or
      in vivo, however molecular mechanisms are not fully elucidated. Particularly,
      little information is available on RSV's effects on metabolic pathways and the
      cell-extra cellular matrix (ECM) communication that are critical for cancer cell
      growth. To identify important targets of RSV, we analyzed whole protein fractions
      from HT-29 advanced human colon cancer cell line treated with solvent control,
      IGF-1 (10 nM) and RSV (150 MUM) using LC/MS/MS-Mud PIT (Multidimensional Protein
      Identification Technology). RESULTS: Pentose phosphate pathway (PPP), a vital
      metabolic pathway for cell cycle progression, was elevated and suppressed by IGF
      1 and RSV, respectively in the HT-29 cell line. Enzymatic assays confirmed RSV
      suppression of glucose-6 phosphate dehydrogenase (rate limiting) and
      transketolase, key enzymes of the PPP. RSV (150 MUM) suppressed, whereas IGF-1
      (10 nM) elevated focal adhesion complex (FAC) proteins, talin and pFAK, critical
      for the cell-ECM communication. Western blotting analyses confirmed the
      suppression or elevation of these proteins in HT-29 cancer cells treated with RSV
      or IGF-1, respectively. CONCLUSIONS: Proteomic analysis enabled us to establish
      PPP and the talin-pFAK as targets of RSV which suppress cancer cell proliferation
      and induce apoptosis in the colon cancer cell line HT-29. RSV (150 MUM)
      suppressed these pathways in the presence and absence of IGF-1, suggesting its
      role as a chemo-preventive agent even in obese condition.

PMID- 21849058
TI  - Biodistribution and blood clearance of plasmid DNA administered in arginine
      peptide complexes.
AB  - BACKGROUND: Peptide/DNA complexes have great potential as non-viral methods for
      gene delivery. Despite promising results for peptide-mediated gene delivery
      technology, an effective systemic peptide-based gene delivery system has not yet
      been developed. METHODS: This study used pCMV-Luc as a model gene to investigate
      the biodistribution and the in vivo efficacy of arginine peptide-mediated gene
      delivery by polymerase chain reaction (PCR). RESULTS: Plasmid DNA was detected in
      all organs tested 1 h after intraperitoneal administration of arginine/DNA
      complexes, indicating that the arginine/DNA complexes disseminated widely through
      the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm
      24 h post administration. The mRNA expression of plasmid DNA was noted in the
      spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs,
      for at least 1 week. Blood clearance studies showed that injected DNA was found
      in the blood as long as 6 h after injection. CONCLUSIONS: Taken together, our
      results demonstrated that arginine/DNA complexes are stable in blood and are
      effective for in vivo gene delivery. These findings suggest that intraperitoneal
      administration of arginine/DNA complexes is a promising tool in gene therapy.

PMID- 21849059
TI  - Cytotoxicity of VEGF(121)/rGel on vascular endothelial cells resulting in
      inhibition of angiogenesis is mediated via VEGFR-2.
AB  - BACKGROUND: The fusion protein VEGF(121)/rGel composed of the growth factor
      VEGF(121) and the plant toxin gelonin targets the tumor neovasculature and exerts
      impressive anti-vascular effects. We have previously shown that VEGF(121)/rGel is
      cytotoxic to endothelial cells overexpressing VEGFR-2 but not to endothelial
      cells overexpressing VEGFR-1. In this study, we examined the basis for the
      specific toxicity of this construct and assessed its intracellular effects in
      vitro and in vivo. METHODS: We investigated the binding, cytotoxicity and
      internalization profile of VEGF(121)/rGel on endothelial cells expressing VEGFR-1
      or VEGFR-2, identified its effects on angiogenesis models in vitro and ex vivo,
      and explored its intracellular effects on a number of molecular pathways using
      microarray analysis. RESULTS: Incubation of PAE/VEGFR-2 and PAE/VEGFR-1 cells
      with (125)I-VEGF(121)/rGel demonstrated binding specificity that was competed
      with unlabeled VEGF(121)/rGel but not with unlabeled gelonin. Assessment of the
      effect of VEGF(121)/rGel on blocking tube formation in vitro revealed a 100-fold
      difference in IC(50) levels between PAE/VEGFR-2 (1 nM) and PAE/VEGFR-1 (100 nM)
      cells. VEGF(121)/rGel entered PAE/VEGFR-2 cells within one hour of treatment but
      was not detected in PAE/VEGFR-1 cells up to 24 hours after treatment. In
      vascularization studies using chicken chorioallantoic membranes, 1 nM
      VEGF(121)/rGel completely inhibited bFGF-stimulated neovascular growth. The
      cytotoxic effects of VEGF(121)/rGel were not apoptotic since treated cells were
      TUNEL-negative with no evidence of PARP cleavage or alteration in the protein
      levels of select apoptotic markers. Microarray analysis of VEGF(121)/rGel-treated
      HUVECs revealed the upregulation of a unique "fingerprint" profile of 22 genes
      that control cell adhesion, apoptosis, transcription regulation, chemotaxis, and
      inflammatory response. CONCLUSIONS: Taken together, these data confirm the
      selectivity of VEGF(121)/rGel for VEGFR-2-overexpressing endothelial cells and
      represent the first analysis of genes governing intoxication of mammalian
      endothelial cells by a gelonin-based targeted therapeutic agent.

PMID- 21849060
TI  - ProbPS: a new model for peak selection based on quantifying the dependence of the
      existence of derivative peaks on primary ion intensity.
AB  - BACKGROUND: The analysis of mass spectra suggests that the existence of
      derivative peaks is strongly dependent on the intensity of the primary peaks.
      Peak selection from tandem mass spectrum is used to filter out noise and
      contaminant peaks. It is widely accepted that a valid primary peak tends to have
      high intensity and is accompanied by derivative peaks, including isotopic peaks,
      neutral loss peaks, and complementary peaks. Existing models for peak selection
      ignore the dependence between the existence of the derivative peaks and the
      intensity of the primary peaks. Simple models for peak selection assume that
      these two attributes are independent; however, this assumption is contrary to
      real data and prone to error. RESULTS: In this paper, we present a statistical
      model to quantitatively measure the dependence of the derivative peak's existence
      on the primary peak's intensity. Here, we propose a statistical model, named
      ProbPS, to capture the dependence in a quantitative manner and describe a
      statistical model for peak selection. Our results show that the quantitative
      understanding can successfully guide the peak selection process. By comparing
      ProbPS with AuDeNS we demonstrate the advantages of our method in both filtering
      out noise peaks and in improving de novo identification. In addition, we present
      a tag identification approach based on our peak selection method. Our results,
      using a test data set, suggest that our tag identification method (876 correct
      tags in 1000 spectra) outperforms PepNovoTag (790 correct tags in 1000 spectra).
      CONCLUSIONS: We have shown that ProbPS improves the accuracy of peak selection
      which further enhances the performance of de novo sequencing and tag
      identification. Thus, our model saves valuable computation time and improving the
      accuracy of the results.

PMID- 21849063
TI  - Optical properties of as-grown and annealed InAs quantum dots on InGaAs cross
      hatch patterns.
AB  - InAs quantum dots (QDs) grown on InGaAs cross-hatch pattern (CHP) by molecular
      beam epitaxy are characterized by photoluminescence (PL) at 20 K. In contrast to
      QDs grown on flat GaAs substrates, those grown on CHPs exhibit rich optical
      features which comprise as many as five ground-state emissions from [1-10]- and
      [110]-aligned QDs, two wetting layers (WLs), and the CHP. When subject to in situ
      annealing at 700 degrees C, the PL signals rapidly degrades due to the
      deterioration of the CHP which sets the upper limit of overgrowth temperature. Ex
      situ hydrogen annealing at a much lower temperature of 350 degrees C, however,
      results in an overall PL intensity increase with a significant narrowing and a
      small blueshift of the high-energy WL emission due to hydrogen bonding which
      neutralizes defects and relieves associated strains.

PMID- 21849061
TI  - The role of androgens in follicle maturation and ovulation induction: friend or
      foe of infertility treatment?
AB  - BACKGROUND: Effects of androgens on follicle maturation have been controversial
      for some time. Here, we review the potential of their applications in improving
      human ovulation induction, based on human and animal data, reported in the
      literature. METHODS: We reviewed the published literature for the years 2005
      2011, using relevant key words, in PubMed, Medline and Cochrane reviews, and then
      performed secondary reviews of referenced articles, which previously had not been
      known or preceded the searched time period. A total of 217 publications were
      reviewed. RESULTS: Contrary to widely held opinion, recent data, mostly developed
      in the mouse, convincingly demonstrate essential contribution of androgens to
      normal follicle maturation and, therefore, female fertility. Androgens appear
      most engaged at preantral and antral stages, primarily affect granulosa cells,
      and exert effects via androgen receptors (AR) through transcriptional regulation
      but also in non-genomic ways, with ligand-activated AR modulating follicle
      stimulating hormone (FSH) activity in granulosa cells. While some androgens, like
      testosterone (T) and dehydroepiandrosterone (DHEA), appear effective in improving
      functional ovarian reserve (FOR) in women with diminished ovarian reserve (DOR),
      others may even exert opposite effects. Such differences in androgens may, at
      least partially, reflect different levels of agonism to AR. DISCUSSION: Selective
      androgens appear capable of improving early stages of folliculogenesis. They,
      therefore, may represent forerunners of a completely new class of ovulation
      inducing medications, which, in contrast to gonadotropins, affect follicle
      maturation at much earlier stages.

PMID- 21849062
TI  - Impact of age on outcome after colorectal cancer surgery in the elderly - a
      developing country perspective.
AB  - BACKGROUND: Colorectal cancer (CRC) is a major source of morbidity and mortality
      in the elderly population and surgery is often the only definitive management
      option. The suitability of surgical candidates based on age alone has
      traditionally been a source of controversy. Surgical resection may be considered
      detrimental in the elderly solely on the basis of advanced age. Based on recent
      evidence suggesting that age alone is not a predictor of outcomes, Western
      societies are increasingly performing definitive procedures on the elderly. Such
      evidence is not available from our region. We aimed to determine whether age has
      an independent effect on complications after surgery for colorectal cancer in our
      population. METHODS: A retrospective review of all patients who underwent surgery
      for pathologically confirmed colorectal cancer at Aga Khan University Hospital,
      Karachi between January 1999 and December 2008 was conducted. Using a cut-off of
      70 years, patients were divided into two groups. Patient demographics, tumor
      characteristics and postoperative complications and 30-day mortality were
      compared. Multivariate logistic regression analysis was performed with clinically
      relevant variables to determine whether age had an independent and significant
      association with the outcome. RESULTS: A total of 271 files were reviewed, of
      which 56 belonged to elderly patients (>= 70 years). The gender ratio was equal
      in both groups. Elderly patients had a significantly higher comorbidity status,
      Charlson score and American society of anesthesiologists (ASA) class (all p <
      0.001). Upon multivariate analysis, factors associated with more complications
      were ASA status (95% CI = 1.30-6.25), preoperative perforation (95% CI = 1.94
      48.0) and rectal tumors (95% CI = 1.21-5.34). Old age was significantly
      associated with systemic complications upon univariate analysis (p = 0.05),
      however, this association vanished upon multivariate analysis (p = 0.36).
      CONCLUSION: Older patients have more co-morbid conditions and higher ASA scores,
      but increasing age itself is not independently associated with complications
      after surgery for CRC. Therefore patient selection should focus on the clinical
      status and ASA class of the patient rather than age.

PMID- 21849064
TI  - Defining the buffering process by a triprotic acid without relying on Stewart
      electroneutrality considerations.
AB  - Upon the addition of protons to an aqueous solution, a component of the H+ load
      will be bound i.e. buffered. In an aqueous solution containing a triprotic acid,
      H+ can be bound to three different states of the acid as well as to OH- ions that
      are derived from the auto-ionization of H2O. In quantifying the buffering process
      of a triprotic acid, one must define the partitioning of H+ among the three
      states of the acid and also the OH- ions in solution in order to predict the
      equilibrium pH value. However, previous quantitative approaches that model
      triprotic acid titration behaviour and used to predict the equilibrium pH rely on
      the mathematical convenience of electroneutrality/charge balance considerations.
      This fact has caused confusion in the literature, and has led to the assumption
      that charge balance/electroneutrality is a causal factor in modulating proton
      buffering (Stewart formulation). However, as we have previously shown, although
      charge balance can be used mathematically as a convenient tool in deriving
      various formulae, electroneutrality per se is not a fundamental physicochemical
      parameter that is mechanistically involved in the underlying buffering and proton
      transfer reactions. The lack of distinction between a mathematical tool, and a
      fundamental physicochemical parameter is in part a reason for the current debate
      regarding the Stewart formulation of acid-base analysis. We therefore posed the
      following question: Is it possible to generate an equation that defines and
      predicts the buffering of a triprotic acid that is based only on H+ partitioning
      without incorporating electroneutrality in the derivation? Towards this goal, we
      derived our new equation utilizing: 1) partitioning of H+ buffering; 2)
      conservation of mass; and 3) acid-base equilibria. In validating this model, we
      compared the predicted equilibrium pH with the measured pH of an aqueous solution
      consisting of Na2HPO4 to which HCl was added. The measured pH values were in
      excellent agreement with the predictions of our equation. Our results provide
      further important evidence that one can mathematically model the chemistry of
      acid-base phenomenology without relying on electroneutrality (Stewart
      formulation) considerations.

PMID- 21849065
TI  - Pattern of BOLD signal in auditory cortex relates acoustic response to perceptual
      streaming.
AB  - BACKGROUND: Segregating auditory scenes into distinct objects or streams is one
      of our brain's greatest perceptual challenges. Streaming has classically been
      studied with bistable sound stimuli, perceived alternately as a single group or
      two separate groups. Throughout the last decade different methodologies have
      yielded inconsistent evidence about the role of auditory cortex in the
      maintenance of streams. In particular, studies using functional magnetic
      resonance imaging (fMRI) have been unable to show persistent activity within
      auditory cortex (AC) that distinguishes between perceptual states. RESULTS: We
      use bistable stimuli, an explicit perceptual categorization task, and a focused
      region of interest (ROI) analysis to demonstrate an effect of perceptual state
      within AC. We find that AC has more activity when listeners perceive the split
      percept rather than the grouped percept. In addition, within this ROI the pattern
      of acoustic response across voxels is significantly correlated with the pattern
      of perceptual modulation. In a whole-brain exploratory test, we corroborate
      previous work showing an effect of perceptual state in the intraparietal sulcus.
      CONCLUSIONS: Our results show that the maintenance of auditory streams is
      reflected in AC activity, directly relating sound responses to perception, and
      that perceptual state is further represented in multiple, higher level cortical
      regions.

PMID- 21849066
TI  - Frequency of human immunodeficiency virus type-2 in hiv infected patients in
      Maputo City, Mozambique.
AB  - The HIV/AIDS pandemic is primarily caused by HIV-1. Another virus type, HIV-2, is
      found mainly in West African countries. We hypothesized that population migration
      and mobility in Africa may have facilitated the introduction and spreading of HIV
      2 in Mozambique. The presence of HIV-2 has important implications for diagnosis
      and choice of treatment of HIV infection. Hence, the aim of this study was to
      estimate the prevalence of HIV-2 infection and its genotype in Maputo,
      Mozambique.HIV-infected individuals (N = 1,200) were consecutively enrolled and
      screened for IgG antibodies against HIV-1 gp41 and HIV-2 gp36 using peptide-based
      enzyme immunoassays (pepEIA). Specimens showing reactivity on the HIV-2 pepEIA
      were further tested using the INNO-LIA immunoblot assay and HIV-2 PCR targeting
      RT and PR genes. Subtype analysis of HIV-2 was based on the protease gene.After
      screening with HIV-2 pepEIA 1,168 were non-reactive and 32 were reactive to HIV-2
      gp36 peptide. Of this total, 30 specimens were simultaneously reactive to gp41
      and gp36 pepEIA while two samples reacted solely to gp36 peptide. Only three
      specimens containing antibodies against gp36 and gp105 on the INNO-LIA immunoblot
      assay were found to be positive by PCR to HIV-2 subtype A.The proportion of HIV-2
      in Maputo City was 0.25% (90%CI 0.01-0.49). The HIV epidemic in Southern
      Mozambique is driven by HIV-1, with HIV-2 also circulating at a marginal rate.
      Surveillance program need to improve HIV-2 diagnosis and consider periodical
      survey aiming to monitor HIV-2 prevalence in the country.

PMID- 21849067
TI  - Kruppel-like factor 6 regulates transforming growth factor-beta gene expression
      during human respiratory syncytial virus infection.
AB  - BACKGROUND: Human respiratory syncytial virus (RSV) infection is associated with
      airway remodeling and subsequent asthma development. Transforming growth factor
      beta (TGF) plays a crucial role in asthma development. The mechanism regulating
      TGF gene expression during RSV infection is not known. Kruppel-like factor family
      of transcription factors are critical regulators of cellular/tissue homeostasis.
      Previous studies have shown that Kruppel-like factor 6 (KLF6) could function as a
      trans-activator of TGF gene; however, whether KLF members play a role during
      infection is unknown. In the current study we have evaluated the role of KLF6
      during TGF expression in RSV infected cells. FINDINGS: Silencing KLF6 expression
      by shRNA led to drastic inhibition in TGF production during RSV infection, as
      assessed by ELISA analysis of medium supernatants. RT-PCR analysis revealed loss
      of TGF expression in KLF6 silenced cells. Chromatin-immunoprecipitation assay
      conducted with RSV infected cells showed binding of KLF6 protein to the TGF
      promoter during RSV infection. We further observed reduced RSV infectivity in
      KLF6 silenced cells and in cells incubated with TGF neutralizing antibody. In
      contrast, enhanced RSV infection was noted in cells incubated with purified TGF.
      CONCLUSION: We have identified KLF6 as a key transcription factor required for
      trans-activation of TGF gene during RSV infection. Moreover, TGF production is
      required for efficient RSV infection and thus, KLF6 is also required for
      efficient RSV infection by virtue of KLF6 dependent TGF production during
      infection.

PMID- 21849068
TI  - Prolapsed sigmoid intussusception per anus in an elderly man: a case report.
AB  - BACKGROUND: Intussusception in pediatrics is widely documented and well
      described. On the basis of the literature, however, adult intussusception is a
      rare entity with a prevalence of from 1% to 5%. The majority of adult patients
      with intussusception have an underlying pathology that needs to be identified by
      performing a proper physical examination and a wide array of investigations. CASE
      PRESENTATION: We present a case of a 66-year-old African man who presented to our
      emergency department with a mass protruding per anus with obstipation. During
      laparotomy, we found that the sigmoid colon had intussuscepted into the rectum
      and out from the anus. Other abdominal viscera were normal and without any
      obvious mesenteric lymphadenopathy. Sigmoid colectomy and spectacle colostomy
      were performed. Grossly, the excised bowel looked normal, but the histologic
      results showed features of necrosis and chronic inflammation. CONCLUSION: While
      70% to 90% of cases of adult intussusception have an identifiable cause or
      lesion, most pediatric intussusceptions are idiopathic. The presentation in an
      adult described herein was of an uncommon idiopathic type with no identifiable
      cause found on the basis of the history, physical examination, or histological
      findings.

PMID- 21849070
TI  - A rapidly progressing Pancoast syndrome due to pulmonary mucormycosis: a case
      report.
AB  - INTRODUCTION: Pancoast syndrome is characterized by Horner syndrome, shoulder
      pain radiating down the arm, compression of the brachial blood vessels, and, in
      long-standing cases, atrophy of the arm and hand muscles. It is most commonly
      associated with lung carcinoma but rarely is seen with certain infections. CASE
      PRESENTATION: We present the case of a 51-year-old Caucasian man who had acute
      myeloid leukemia and who developed a rapidly fulminating pneumonia along with
      signs and symptoms of acute brachial plexopathy and left Horner syndrome. Also, a
      purpuric plaque developed over his left chest wall and progressed to skin
      necrosis. The skin biopsy and bronchoalveolar lavage showed a Rhizopus species,
      leading to a diagnosis of mucormycosis. This is a rare case of pneumonia due to
      mucormycosis associated with acute Pancoast syndrome. CONCLUSIONS: According to
      our review of the literature, only a few infectious agents have been reported to
      be associated with Pancoast syndrome. We found only three case reports of
      mucormycosis associated with acute Pancoast syndrome. Clinicians should consider
      mucormycosis in their differential diagnosis in a patient with pulmonary lesions
      and chest wall invasion with or without neurological symptoms, especially in the
      setting of neutropenia or other immunosuppressed conditions. It is important to
      recognize this condition early in order to target therapy and interventions.

PMID- 21849069
TI  - Early monitoring of the human polyomavirus BK replication and sequencing analysis
      in a cohort of adult kidney transplant patients treated with basiliximab.
AB  - BACKGROUND: Nowadays, better immunosuppressors have decreased the rates of acute
      rejection in kidney transplantation, but have also led to the emergence of BKV
      associated nephropathy (BKVAN). Therefore, we prospectively investigated BKV load
      in plasma and urine samples in a cohort of kidney transplants, receiving
      basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to
      evaluate the difference between BKV replication during the first 3 months post
      transplantation, characterized by the non-depleting action of basiliximab, versus
      the second 3 months, in which the maintenance therapy acts alone. We also
      performed sequencing analysis to assess whether a particular BKV subtype/subgroup
      or transcriptional control region (TCR) variants were present. METHODS: We
      monitored BK viruria and viremia by quantitative polymerase chain reaction (Q
      PCR) at 12 hours (Tx), 1 (T1), 3 (T2) and 6 (T3) months post-transplantation
      among 60 kidney transplant patients. Sequencing analysis was performed by nested
      PCR with specific primers for TCR and VP1 regions. Data were statistically
      analyzed using chi2 test and Student's t-test. RESULTS: BKV was detected at Tx in
      4/60 urine and in 16/60 plasma, with median viral loads of 3.70 log GEq/mL and
      3.79 log GEq/mL, respectively, followed by a significant increase of both BKV
      positive transplants (32/60) and median values of viruria (5.78 log GEq/mL) and
      viremia (4.52 log GEq/mL) at T2. Conversely, a significantly decrease of patients
      with viruria and viremia (17/60) was observed at T3, together with a reduction of
      the median urinary and plasma viral loads (4.09 log GEq/mL and 4.00 log GEq/mL,
      respectively). BKV TCR sequence analysis always showed the presence of archetypal
      sequences, with a few single-nucleotide substitutions and one nucleotide
      insertion that, interestingly, were all representative of the particular
      subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2.
      CONCLUSIONS: Our results confirm previous studies indicating that BKV replication
      may occur during the early hours after kidney transplantation, reaches the
      highest incidence in the third post-transplantation month and then decreases
      within the sixth month, maybe due to induction therapy. Moreover, it might become
      clinically useful whether specific BKV subtypes or rearrangements could be linked
      to a particular disease state in order to detect them before BKVAN onset.

PMID- 21849071
TI  - The injury epidemiology of cyclists based on a road trauma registry.
AB  - BACKGROUND: Bicycle use has increased in some of France's major cities, mainly as
      a means of transport. Bicycle crashes need to be studied, preferably by type of
      cycling. Here we conduct a descriptive analysis. METHOD: A road trauma registry
      has been in use in France since 1996, in a large county around Lyon (the Rhone,
      population 1.6 million). It covers outpatients, inpatients and fatalities. All
      injuries are coded using the Abbreviated Injury Scale (AIS). Proxies were used to
      identify three types of cycling: learning = children (0-10 years old); sports
      cycling = teenagers and adults injured outside towns; cycling as means of
      transport = teenagers and adults injured in towns. The study is based on 13,684
      cyclist casualties (1996-2008). RESULTS: The percentage of cyclists injured in a
      collision with a motor vehicle was 8% among children, 17% among teenagers and
      adults injured outside towns, and 31% among those injured in towns. The
      percentage of serious casualties (MAIS 3+) was 4.5% among children, 10.9% among
      adults injured outside towns and 7.2% among those injured in towns. Collisions
      with motor-vehicles lead to more internal injuries than bicycle-only crashes.
      CONCLUSION: The description indicates that cyclist type is associated with
      different crash and injury patterns. In particular, cyclists injured in towns
      (where cycling is increasing) are generally less severely injured than those
      injured outside towns for both types of crash (bicycle-only crashes and
      collisions with a motor vehicle). This is probably due to lower speeds in towns,
      for both cyclists and motor vehicles.

PMID- 21849072
TI  - Atomic resolution structure of EhpR: phenazine resistance in Enterobacter
      agglomerans Eh1087 follows principles of bleomycin/mitomycin C resistance in
      other bacteria.
AB  - BACKGROUND: The phenazines are redox-active secondary metabolites that a large
      number of bacterial strains produce and excrete into the environment. They
      possess antibiotic activity owing to the fact that they can reduce molecular
      oxygen to toxic reactive oxygen species. In order to take advantage of this
      activity, phenazine producers need to protect themselves against phenazine
      toxicity. Whereas it is believed that phenazine-producing pseudomonads possess
      highly active superoxide dismutases and catalases, it has recently been found
      that the plant-colonizing bacterium Enterobacter agglomerans expresses a small
      gene ehpR to render itself resistant towards D-alanyl-griseoluteic acid, the
      phenazine antibiotic produced by this strain. RESULTS: To understand the
      resistance mechanism installed by EhpR we have determined its crystal structure
      in the apo form at 2.15 A resolution and in complex with griseoluteic acid at
      1.01 A, respectively. While EhpR shares a common fold with glyoxalase-I/bleomycin
      resistance proteins, the ligand binding site does not contain residues that some
      related proteins employ to chemically alter their substrates. Binding of the
      antibiotic is mediated by pi-stacking interactions of the aromatic moiety with
      the side chains of aromatic amino acids and by a few polar interactions. The
      dissociation constant KD between EhpR and griseoluteic acid was quantified as 244
      +/- 45 MUM by microscale thermophoresis measurements. CONCLUSIONS: The data
      accumulated here suggest that EhpR confers resistance by binding D-alanyl
      griseoluteic acid and acting as a chaperone involved in exporting the antibiotic
      rather than by altering it chemically. It is tempting to speculate that EhpR acts
      in concert with EhpJ, a transport protein of the major facilitator superfamily
      that is also encoded in the phenazine biosynthesis operon of E. agglomerans. The
      low affinity of EhpR for griseoluteic acid may be required for its physiological
      function.

PMID- 21849073
TI  - Generation of high-titer viral preparations by concentration using successive
      rounds of ultracentrifugation.
AB  - BACKGROUND: Viral vectors provide a method of stably introducing exogenous DNA
      into cells that are not easily transfectable allowing for the ectopic expression
      or silencing of genes for therapeutic or experimental purposes. However, some
      cell types, in particular bone marrow cells, dendritic cells and neurons are
      difficult to transduce with viral vectors. Successful transduction of such cells
      requires preparation of highly concentrated viral stocks, which permit a high
      virus concentration and multiplicity of infection (MOI) during transduction.
      Pseudotyping with the vesicular stomatitis virus G (VSV-G) envelope protein is
      common practice for both lentiviral and retroviral vectors. The VSV-G
      glycoprotein adds physical stability to retroviral particles, allowing
      concentration of virus by high-speed ultracentrifugation. Here we describe a
      method report for concentration of virus from large volumes of culture
      supernatant by means of successive rounds of ultracentrifugation into the same
      ultracentrifuge tube. METHOD: Stable retrovirus producer cell lines were
      generated and large volumes of virus-containing supernatant were produced. We
      then tested the transduction ability of virus following varying rounds of
      concentration by ultra-centrifugation. In a second series of experiments
      lentivirus-containing supernatant was produced by transient transfection of
      297T/17 cells and again we tested the transduction ability of virus following
      multiple rounds of ultra-centrifugation. RESULTS: We report being able to
      centrifuge VSV-G coated retrovirus for as many as four rounds of
      ultracentrifugation while observing an additive increase in viral titer. Even
      after four rounds of ultracentrifugation we did not reach a plateau in viral
      titer relative to viral supernatant concentrated to indicate that we had reached
      the maximum tolerated centrifugation time, implying that it may be possible to
      centrifuge VSV-G coated retrovirus even further should it be necessary to achieve
      yet higher titers for specific applications. We further report that VSV-G coated
      lentiviral particles may also be concentrated by successive rounds of
      ultracentrifugation (in this case four rounds) with minimal loss of transduction
      efficiency. CONCLUSION: This method of concentrating virus has allowed us to
      generate virus of sufficient titers to transduce bone marrow cells with both
      retrovirus and lentivirus, including virus carrying shRNA constructs.

PMID- 21849074
TI  - Real-time PCR detection of human herpesvirus 1-5 in patients lacking clinical
      signs of a viral CNS infection.
AB  - BACKGROUND: Infections of the central nervous system (CNS) with herpes- or
      enterovirus can be self-limiting and benign, but occasionally result in severe
      and fatal disease. The polymerase chain reaction (PCR) has revolutionized the
      diagnostics of viral pathogens, and by multiple displacement amplification (MDA)
      prior to real-time PCR the sensitivity might be further enhanced. The aim of this
      study was to investigate if herpes- or enterovirus can be detected in
      cerebrospinal fluid (CSF) from patients without symptoms. METHODS: Cerebrospinal
      fluid (CSF) samples from 373 patients lacking typical symptoms of viral CNS
      infection were analysed by real-time PCR targeting herpesviruses or enteroviruses
      with or without prior MDA. RESULTS: In total, virus was detected in 17 patients
      (4%). Epstein-Barr virus (EBV) was most commonly detected, in general from
      patients with other conditions (e.g. infections, cerebral hemorrhage). MDA
      satisfactorily amplified viral DNA in the absence of human nucleic acids, but
      showed poor amplification capacity for viral DNA in CSF samples, and did not
      increase the sensitivity for herpes virus-detection with our methodology.
      CONCLUSIONS: Viral pathogens are rarely detected in CSF from patients without
      signs of CNS infection, supporting the view that real-time PCR is a highly
      specific method to detect symptomatic CNS-infection caused by these viruses.
      However, EBV may be subclinically reactivated due to other pathological
      conditions in the CNS.

PMID- 21849075
TI  - Legionella pneumophila serogroup 3 pneumonia in a patient with low-grade 4 non
      Hodgkin lymphoma: a case report.
AB  - INTRODUCTION: Nosocomial legionellosis has generally been described in
      immunodepressed patients, but Legionella pneumophila serogroup 3 has rarely been
      identified as the causative agent. CASE PRESENTATION: We report the case of
      nosocomial L. pneumophila serogroup 3 pneumonia in a 70-year-old Caucasian man
      with non-Hodgkin lymphoma. Diagnosis was carried out by culture and real-time
      polymerase chain reaction of bronchoalveolar lavage fluid. The results of a
      urinary antigen test were negative. A hospital environmental investigation
      revealed that the hospital water system was highly colonized by L. pneumophila
      serogroups 3, 4, and 8. The hospital team involved in the prevention of
      infections was informed, long-term control measures to reduce the environmental
      bacterial load were adopted, and clinical monitoring of legionellosis occurrence
      in high-risk patients was performed. No further cases of Legionella pneumonia
      have been observed so far. CONCLUSIONS: In this report, we describe a case of
      legionellosis caused by L. pneumophila serogroup 3, which is not usually a
      causative agent of nosocomial infection. Our research confirms the importance of
      carrying out cultures of respiratory secretions to diagnose legionellosis and
      highlights the limited value of the urinary antigen test for hospital infections,
      especially in immunocompromised patients. It also indicates that, to reduce the
      bacterial load and prevent nosocomial legionellosis, appropriate control measures
      should be implemented with systematic monitoring of hospital water systems.

PMID- 21849076
TI  - Serum testosterone levels of HbSS (sickle cell disease) male subjects in Lagos,
      Nigeria.
AB  - BACKGROUND: Infertility is a major problem in sickle cell disease patients,
      especially in males. In addition to low serum testosterone, other abnormalities
      involving the accessory sex organs, such as the seminal vesicles and the prostate
      gland, as well as marked decrease in ejaculate volume may be observed in male
      HbSS patients. Hence, the need to study the role of sex hormones as a cause of
      infertility in male HbSS patients. METHODS: An unmatched case-control study was
      performed using seventy-five consenting subjects from Lagos University Teaching
      Hospital. These included 47 patients with haemoglobin phenotype SS from the
      Sickle cell clinic and 28 volunteered medical students and members of staff with
      haemoglobin phenotype AA. Demographic data were obtained using a self
      administered questionnaire. A total of 5 mls of blood was collected from each
      subject between 9.00 am & 11.am, and assayed for serum testosterone
      concentration. RESULTS: The concentrations of serum testosterone in HbSS patients
      ranged from 0.2 to 4.3 ng/ml with a mean of 1.28 +/- 0.72 ng/ml whilst the values
      in HbAA controls ranged from 1.2 to 6.9 ng/ml with a mean of 2.63 +/- 1.04 ng/ml.
      Seven (25.0%) of the 28 controls had serum testosterone concentration lower than
      the quoted reference (normal) range whereas 44 (93.6%) of the 47 HbSS subjects
      had serum testosterone concentration lower than the reference range. CONCLUSION:
      Overall, subjects with HbSS have significantly lower mean serum testosterone than
      HbAA controls.

PMID- 21849077
TI  - An alternative route for the synthesis of silicon nanowires via porous anodic
      alumina masks.
AB  - Amorphous Si nanowires have been directly synthesized by a thermal processing of
      Si substrates. This method involves the deposition of an anodic aluminum oxide
      mask on a crystalline Si (100) substrate. Fe, Au, and Pt thin films with
      thicknesses of ca. 30 nm deposited on the anodic aluminum oxide-Si substrates
      have been used as catalysts. During the thermal treatment of the samples, thin
      films of the metal catalysts are transformed in small nanoparticles incorporated
      within the pore structure of the anodic aluminum oxide mask, directly in contact
      with the Si substrate. These homogeneously distributed metal nanoparticles are
      responsible for the growth of Si nanowires with regular diameter by a simple
      heating process at 800 degrees C in an Ar-H2 atmosphere and without an additional
      Si source. The synthesized Si nanowires have been characterized by field emission
      scanning electron microscopy, high-resolution transmission electron microscopy, X
      ray photoelectron spectroscopy, and Raman.

PMID- 21849078
TI  - Collaborative care for patients with bipolar disorder: a randomised controlled
      trial.
AB  - BACKGROUND: Bipolar disorder is a severe mental illness with serious consequences
      for daily living of patients and their caregivers. Care as usual primarily
      consists of pharmacotherapy and supportive treatment. However, a substantial
      number of patients show a suboptimal response to treatment and still suffer from
      frequent episodes, persistent interepisodic symptoms and poor social functioning.
      Both psychiatric and somatic comorbid disorders are frequent, especially
      personality disorders, substance abuse, cardiovascular diseases and diabetes.
      Multidisciplinary collaboration of professionals is needed to combine all
      expertise in order to achieve high-quality integrated treatment. 'Collaborative
      Care' is a treatment method that could meet these needs. Several studies have
      shown promising effects of these integrated treatment programs for patients with
      bipolar disorder. In this article we describe a research protocol concerning a
      study on the effects of Collaborative Care for patients with bipolar disorder in
      the Netherlands. METHODS/DESIGN: The study concerns a two-armed cluster
      randomised clinical trial to evaluate the effectiveness of Collaborative Care
      (CC) in comparison with Care as usual (CAU) in outpatient clinics for bipolar
      disorder or mood disorders in general. Collaborative Care includes individually
      tailored interventions, aimed at personal goals set by the patient. The patient,
      his caregiver, the nurse and the psychiatrist all are part of the Collaborative
      Care team. Elements of the program are: contracting and shared decision making;
      psycho education; problem solving treatment; systematic relapse prevention;
      monitoring of outcomes and pharmacotherapy. Nurses coordinate the program. Nurses
      and psychiatrists in the intervention group will be trained in the intervention.
      The effects will be measured at baseline, 6 months and 12 months. Primary
      outcomes are psychosocial functioning, psychiatric symptoms, and quality of life.
      Caregiver outcomes are burden and satisfaction with care. DISCUSSION: Several
      ways to enhance the quality of this study are described, as well as some
      limitations caused by the complexities of naturalistic treatment settings where
      not all influencing factors on an intervention and the outcomes can be
      controlled. TRIAL REGISTRATION: The Netherlands Trial Registry, NTR2600.

PMID- 21849079
TI  - Monitoring the wild black bear's reaction to human and environmental stressors.
AB  - BACKGROUND: Bears are among the most physiologically remarkable mammals. They
      spend half their life in an active state and the other half in a state of
      dormancy without food or water, and without urinating, defecating, or physical
      activity, yet can rouse and defend themselves when disturbed. Although important
      data have been obtained in both captive and wild bears, long-term physiological
      monitoring of bears has not been possible until the recent advancement of
      implantable devices. RESULTS: Insertable cardiac monitors that were developed for
      use in human heart patients (Reveal(r) XT, Medtronic, Inc) were implanted in 15
      hibernating bears. Data were recovered from 8, including 2 that were legally shot
      by hunters. Devices recorded low heart rates (pauses of over 14 seconds) and low
      respiration rates (1.5 breaths/min) during hibernation, dramatic respiratory
      sinus arrhythmias in the fall and winter months, and elevated heart rates in
      summer (up to 214 beats/min (bpm)) and during interactions with hunters
      (exceeding 250 bpm). The devices documented the first and last day of denning, a
      period of quiescence in two parturient females after birthing, and extraordinary
      variation in the amount of activity/day, ranging from 0 (winter) to 1084 minutes
      (summer). Data showed a transition toward greater nocturnal activity in the fall,
      preceding hibernation. The data-loggers also provided evidence of the
      physiological and behavioral responses of bears to our den visits to retrieve the
      data. CONCLUSIONS: Annual variations in heart rate and activity have been
      documented for the first time in wild black bears. This technique has broad
      applications to wildlife management and physiological research, enabling the
      impact of environmental stressors from humans, changing seasons, climate change,
      social interactions and predation to be directly monitored over multiple years.

PMID- 21849080
TI  - Early detection and intervention using neutrophil gelatinase-associated lipocalin
      (NGAL) may improve renal outcome of acute contrast media induced nephropathy: a
      randomized controlled trial in patients undergoing intra-arterial angiography
      (ANTI-CIN Study).
AB  - BACKGROUND: Patients with pre-existing impaired renal function are prone to
      develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase
      associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury
      (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary
      NGAL values may be markedly increased in chronic renal failure at baseline.
      Results from those studies suggested that urinary NGAL values may not be helpful
      for the clinician. An intravenous volume load is a widely accepted prophylactic
      measure and possibly a reasonable intervention to prevent deterioration of renal
      function. The aim of our study is to evaluate NGAL as an early predictor of CIN
      and to investigate the clinical benefit of early post-procedural i.v. hydration.
      METHODS/DESIGN: The study will follow a prospective, open-label, randomized
      controlled design. Patients requiring intra-arterial contrast media (CM)
      application will be included and receive standardized, weight-based, intravenous
      hydration before investigation. Subjects with markedly increased urinary NGAL
      values after CM application will be randomized into one of two study groups.
      Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group
      B will undergo only standard treatment consisting of unrestricted oral fluid
      intake. The primary outcome measure will be CIN defined by an increase greater
      than 25% of baseline serum creatinine. Secondary outcomes will include urinary
      NGAL values, cystatin C values, contrast media associated changes in cardiac
      parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for
      renal replacement treatment, length of stay in hospital and death.We assume that
      20% of the included patients will show a definite rise in urinary NGAL.
      Prospective statistical power calculations indicate that the study will have 80%
      statistical power to detect a clinically significant decrease of CIN of 40% in
      the treatment arm if 1200 patients are recruited into the study. DISCUSSION: A
      volume expansion strategy showing a benefit from earlier intervention for
      patients with markedly elevated urinary NGAL values, indicating a CIN, might
      arise from data from this study. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01292317.

PMID- 21849082
TI  - A cohort study of short-term functional outcomes following injury: the role of
      pre-injury socio-demographic and health characteristics, injury and injury
      related healthcare.
AB  - BACKGROUND: Injury outcome studies have tended to collect limited pre-injury
      characteristics, focus on a narrow range of injury types, predictors and
      outcomes, and be restricted to high threat to life injuries. We sought to
      identify the role of pre-injury socio-demographic and health characteristics,
      injury and injury-related healthcare in determining short-term functional
      outcomes for a wide range of injuries. METHODS: Study participants (aged 18-64
      years inclusive) were those in the Prospective Outcomes of Injury Study, a cohort
      of 2856 persons who were injured and registered with New Zealand's national no
      fault injury insurance agency. All information used in this paper was obtained
      directly from the participants, primarily by telephone interviews, approximately
      three months after their injury. The functional outcomes of interest were the
      five dimensions of the EQ-5D plus a cognitive dimension. We initially examined
      bivariate relationships between our independent measures and the dependent
      measures. Our multivariate analyses included adjustment for pre-injury EQ-5D
      status and time between injury and when information was obtained from
      participants. RESULTS: Substantial portions of participants continued to have
      adverse outcomes approximately three months after their injury. Key pervasive
      factors predicting adverse outcomes were: being female, prior chronic illness,
      injuries to multiple body regions, being hospitalized for injury, self-perceived
      threat to life, and difficulty accessing health services. CONCLUSION: Future
      injury outcome studies should include participants whose injuries are considered
      'minor', as judged by acute health service utilization, and also consider a wider
      range of potential predictors of adverse outcomes.

PMID- 21849081
TI  - Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients
      from six African countries enrolled in two randomized anti-malarial clinical
      trials.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in
      populations living in malaria endemic areas. G6PD genotype and phenotype were
      determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate
      (CDA) phase III clinical trial programme. METHODS: Study participants, aged > 1
      year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria,
      and haemoglobin >= 70 g/L or haematocrit >= 25%, were recruited into two clinical
      trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria,
      Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B,
      G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and
      used for frequency estimation. G6PD phenotype was assessed qualitatively using
      the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD
      status on baseline haemoglobin concentration, temperature, asexual parasitaemia
      and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or
      chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six
      dose artemether-lumefantrine. RESULTS: Of 2264 malaria patients enrolled, 2045
      had G6PD genotype available and comprised the primary analysis population (1018
      males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N =
      147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of
      patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All
      deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for
      64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6%
      (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity
      in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous
      females. Logistic regression found no significant effect of G6PD genotype on
      adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline
      temperature (p = 0.9617), or adjusted log mean baseline parasitaemia (p = 0.365).
      There was no effect of G6PD genotype (p = 0.490) or phenotype (p = 0.391) on the
      rate of malaria recrudescence, or reinfection (p = 0.134 and p = 0.354,
      respectively). CONCLUSIONS: G6PD deficiency is common in African patients with
      malaria and until a reliable and simple G6PD test is available, the use of 8
      aminoquinolines will remain problematic. G6PD status did not impact baseline
      haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial
      therapy. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00344006 and NCT00371735.

PMID- 21849083
TI  - Awakening Australia to Rare Diseases: symposium report and preliminary outcomes.

PMID- 21849084
TI  - III-Nitride grating grown on freestanding HfO2 gratings.
AB  - We report here the epitaxial growth of III-nitride material on freestanding HfO2
      gratings by molecular beam epitaxy. Freestanding HfO2 gratings are fabricated by
      combining film evaporation, electron beam lithography, and fast atom beam etching
      of an HfO2 film by a front-side silicon process. The 60-MUm long HfO2 grating
      beam can sustain the stress change during the epitaxial growth of a III-nitride
      material. Grating structures locally change the growth condition and vary indium
      composition in the InGaN/GaN quantum wells and thus, the photoluminescence
      spectra of epitaxial III-nitride grating are tuned. Guided mode resonances are
      experimentally demonstrated in fabricated III-nitride gratings, opening the
      possibility to achieve the interaction between the excited light and the grating
      structure through guided mode resonance.PACS: 78.55.Cr; 81.65.Cf; 81.15.Hi.

PMID- 21849085
TI  - Localization of chondromodulin-I at the feto-maternal interface and its
      inhibitory actions on trophoblast invasion in vitro.
AB  - BACKGROUND: Chondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is
      specifically localized at the extracellular matrix of the avascular mesenchyme
      including cartilage and cardiac valves. In this study, we characterized the
      expression pattern of ChM-I during early pregnancy in mice in vivo and its effect
      on invasion of trophoblastic cells into Matrigel in vitro. RESULTS: Northern blot
      analysis clearly indicated that ChM-I transcripts were expressed in the pregnant
      mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and
      immunohistochemistry revealed that ChM-I was localized to the mature decidua
      surrounding the matrix metalloproteinase-9 (MMP-9)-expressing trophoblasts.
      Consistent with this observation, the expression of ChM-I mRNA was induced in
      decidualizing endometrial stromal cells in vitro, in response to estradiol and
      progesterone. Recombinant human ChM-I (rhChM-I) markedly inhibited the invasion
      through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast
      cells in a manner independent of MMP activation. CONCLUSIONS: This study
      demonstrates the inhibitory action of ChM-I on trophoblast migration and
      invasion, implying the potential role of the ChM-I expression in decidual cells
      for the regulated tissue remodeling and angiogenesis at feto-maternal interface.

PMID- 21849086
TI  - Evolutionary versatility of eukaryotic protein domains revealed by their bigram
      networks.
AB  - BACKGROUND: Protein domains are globular structures of independently folded
      polypeptides that exert catalytic or binding activities. Their sequences are
      recognized as evolutionary units that, through genome recombination, constitute
      protein repertoires of linkage patterns. Via mutations, domains acquire modified
      functions that contribute to the fitness of cells and organisms. Recent studies
      have addressed the evolutionary selection that may have shaped the functions of
      individual domains and the emergence of particular domain combinations, which led
      to new cellular functions in multi-cellular animals. This study focuses on
      modeling domain linkage globally and investigates evolutionary implications that
      may be revealed by novel computational analysis. RESULTS: A survey of 77
      completely sequenced eukaryotic genomes implies a potential hierarchical and
      modular organization of biological functions in most living organisms. Domains in
      a genome or multiple genomes are modeled as a network of hetero-duplex covalent
      linkages, termed bigrams. A novel computational technique is introduced to
      decompose such networks, whereby the notion of domain "networking versatility" is
      derived and measured. The most and least "versatile" domains (termed "core
      domains" and "peripheral domains" respectively) are examined both computationally
      via sequence conservation measures and experimentally using selected domains. Our
      study suggests that such a versatility measure extracted from the bigram networks
      correlates with the adaptivity of domains during evolution, where the network
      core domains are highly adaptive, significantly contrasting the network
      peripheral domains. CONCLUSIONS: Domain recombination has played a major part in
      the evolution of eukaryotes attributing to genome complexity. From a system point
      of view, as the results of selection and constant refinement, networks of domain
      linkage are structured in a hierarchical modular fashion. Domains with high
      degree of networking versatility appear to be evolutionary adaptive, potentially
      through functional innovations. Domain bigram networks are informative as a model
      of biological functions. The networking versatility indices extracted from such
      networks for individual domains reflect the strength of evolutionary selection
      that the domains have experienced.

PMID- 21849087
TI  - Indigenous utilization of termite mounds and their sustainability in a rice
      growing village of the central plain of Laos.
AB  - BACKGROUND: The objective of this study was to investigate the indigenous
      utilization of termite mounds and termites in a rain-fed rice growing village in
      the central plain of Laos, where rice production is low and varies year-to-year,
      and to assess the possibility of sustainable termite mound utilization in the
      future. This research was carried out from 2007 to 2009. METHODS: The termites
      were collected from their mounds and surrounding areas and identified. Twenty
      villagers were interviewed on their use of termites and their mounds in the
      village. Sixty-three mounds were measured to determine their dimensions in early
      March, early July and middle to late November, 2009. RESULTS: Eleven species of
      Termitidae were recorded during the survey period. It was found that the
      villagers use termite mounds as fertilizer for growing rice, vegetable beds and
      charcoal kilns. The villagers collected termites for food and as feed for
      breeding fish. Over the survey period, 81% of the mounds surveyed increased in
      volume; however, the volume was estimated to decrease by 0.114 m3 mound(-1) year(
      1) on average due to several mounds being completely cut out. CONCLUSION: It was
      concluded that current mound utilization by villagers is not sustainable. To
      ensure sustainable termite utilization in the future, studies should be conducted
      to enhance factors that promote mound restoration by termites. Furthermore, it
      will be necessary to improve mound conservation methods used by the villagers
      after changes in the soil mass of mounds in paddy fields and forests has been
      measured accurately. The socio-economic factors that affect mound utilization
      should also be studied.

PMID- 21849088
TI  - A compressed sensing-based iterative algorithm for CT reconstruction and its
      possible application to phase contrast imaging.
AB  - BACKGROUND: Computed Tomography (CT) is a technology that obtains the tomogram of
      the observed objects. In real-world applications, especially the biomedical
      applications, lower radiation dose have been constantly pursued. To shorten
      scanning time and reduce radiation dose, one can decrease X-ray exposure time at
      each projection view or decrease the number of projections. Until quite recently,
      the traditional filtered back projection (FBP) method has been commonly exploited
      in CT image reconstruction. Applying the FBP method requires using a large amount
      of projection data. Especially when the exposure speed is limited by the
      mechanical characteristic of the imaging facilities, using FBP method may prolong
      scanning time and cumulate with a high dose of radiation consequently damaging
      the biological specimens. METHODS: In this paper, we present a compressed sensing
      based (CS-based) iterative algorithm for CT reconstruction. The algorithm
      minimizes the l1-norm of the sparse image as the constraint factor for the
      iteration procedure. With this method, we can reconstruct images from
      substantially reduced projection data and reduce the impact of artifacts
      introduced into the CT reconstructed image by insufficient projection
      information. RESULTS: To validate and evaluate the performance of this CS-base
      iterative algorithm, we carried out quantitative evaluation studies in imaging of
      both software Shepp-Logan phantom and real polystyrene sample. The former is
      completely absorption based and the later is imaged in phase contrast. The
      results show that the CS-based iterative algorithm can yield images with quality
      comparable to that obtained with existing FBP and traditional algebraic
      reconstruction technique (ART) algorithms. DISCUSSION: Compared with the common
      reconstruction from 180 projection images, this algorithm completes CT
      reconstruction from only 60 projection images, cuts the scan time, and maintains
      the acceptable quality of the reconstructed images.

PMID- 21849089
TI  - Improved accuracy of co-morbidity coding over time after the introduction of ICD
      10 administrative data.
AB  - BACKGROUND: Co-morbidity information derived from administrative data needs to be
      validated to allow its regular use. We assessed evolution in the accuracy of
      coding for Charlson and Elixhauser co-morbidities at three time points over a 5
      year period, following the introduction of the International Classification of
      Diseases, 10th Revision (ICD-10), coding of hospital discharges. METHODS: Cross
      sectional time trend evaluation study of coding accuracy using hospital chart
      data of 3'499 randomly selected patients who were discharged in 1999, 2001 and
      2003, from two teaching and one non-teaching hospital in Switzerland. We measured
      sensitivity, positive predictive and Kappa values for agreement between
      administrative data coded with ICD-10 and chart data as the 'reference standard'
      for recording 36 co-morbidities. RESULTS: For the 17 the Charlson co-morbidities,
      the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2
      64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities,
      the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6%
      (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30
      co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities
      was statistically significant for six conditions and the decrease significant for
      one. Kappa values were increased for 29 co-morbidities and decreased for seven.
      CONCLUSIONS: Accuracy of administrative data in recording clinical conditions
      improved slightly between 1999 and 2003. These findings are of relevance to all
      jurisdictions introducing new coding systems, because they demonstrate a
      phenomenon of improved administrative data accuracy that may relate to a coding
      'learning curve' with the new coding system.

PMID- 21849090
TI  - Ghost Ileostomy with or without abdominal parietal split.
AB  - BACKGROUND: In patients who undergo low anterior rectal resection, the fashioning
      of a covering stoma (CS) is still controversial. In fact, a covering stoma
      (ileostomy or colostomy) is worsened by major complications related to the
      procedure, longer recovery time, necessity of a re-intervention under general
      anesthesia for stoma closure and poorer quality of life. The advantage of Ghost
      Ileostomy (GI) is that an ileostomy can be performed only when there is clinical
      evidence of anastomotic leakage, without performing further interventions with
      related complications when anastomotic leak is absent and therefore the procedure
      is not necessary. Moreover, in case of anastomotic dehiscence and necessity of
      delayed stoma opening, mortality and morbidity in patients with GI are comparable
      with the ones that occur in patients which had a classic covering stoma. On the
      other hand, is simple to think about the possible economic saving: avoiding an
      admission for performing the closure of the ileostomy, with all the costs
      connected (OR, hospitalization, post-operative period, treatment of possible
      complications) represents a huge saving for the hospital management and also
      raise the quality of life of the patients. METHODS: In this study we
      prospectively analyzed 20 patients who underwent anterior extra-peritoneal rectum
      resection for rectal carcinoma with TME and fashioning of GI realized with or
      without abdominal parietal split. RESULTS: In the group of patients that received
      a GI without split laparotomy mortality was absent and in one case an anastomotic
      leak occurred. In the group of patients in which GI with split laparotomy was
      fashioned, one death occurred and there were one case of infection and one
      respiratory complication. Clinical follow-up was 12 months. CONCLUSIONS: The use
      of different techniques for fashioning a GI do not present significant
      differences when they are performed by expert surgeons, but further evidence is
      needed with more randomized trials, in order to have more data supporting the
      clinical observation.

PMID- 21849091
TI  - Global gene expression profiling of Plasmodium falciparum in response to the anti
      malarial drug pyronaridine.
AB  - BACKGROUND: Pyronaridine (PN) and chloroquine (CQ) are structurally related anti
      malarial drugs with primarily the same mode of action. However, PN is effective
      against several multidrug-resistant lines of Plasmodium falciparum, including CQ
      resistant lines, suggestive of important operational differences between the two
      drugs. METHODS: Synchronized trophozoite stage cultures of P. falciparum strain
      K1 (CQ resistant) were exposed to 50% inhibitory concentrations (IC50) of PN and
      CQ, and parasites were harvested from culture after 4 and 24 hours exposure.
      Global transcriptional changes effected by drug treatment were investigated using
      DNA microarrays. RESULTS: After a 4 h drug exposure, PN induced a greater degree
      of transcriptional perturbation (61 differentially expressed features) than CQ
      (10 features). More genes were found to respond to 24 h treatments with both
      drugs, and 461 features were found to be significantly responsive to one or both
      drugs across all treatment conditions. Filtering was employed to remove features
      unrelated to primary drug action, specifically features representing genes
      developmentally regulated, secondary stress/death related processes and sexual
      stage development. The only significant gene ontologies represented among the 46
      remaining features after filtering relate to host exported proteins from multi
      gene families. CONCLUSIONS: The malaria parasite's molecular responses to PN and
      CQ treatment are similar in terms of the genes and pathways affected. However, PN
      appears to exert a more rapid response than CQ. The faster action of PN may
      explain why PN is more efficacious than CQ, particularly against CQ resistant
      isolates. In agreement with several other microarray studies of drug action on
      the parasite, it is not possible, however, to discern mechanism of drug action
      from the drug-responsive genes.

PMID- 21849092
TI  - A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell
      membrane to induce rapid killing of cancer cells.
AB  - BACKGROUND: Transferrin receptor (TfR) is a cell membrane-associated glycoprotein
      involved in the cellular uptake of iron and the regulation of cell growth. Recent
      studies have shown the elevated expression levels of TfR on cancer cells compared
      with normal cells. The elevated expression levels of this receptor in
      malignancies, which is the accessible extracellular protein, can be a fascinating
      target for the treatment of cancer. We have recently designed novel type of
      immunotoxin, termed "hybrid peptide", which is chemically synthesized and is
      composed of target-binding peptide and lytic peptide containing cationic-rich
      amino acids components that disintegrates the cell membrane for the cancer cell
      killing. The lytic peptide is newly designed to induce rapid killing of cancer
      cells due to conformational change. In this study, we designed TfR binding
      peptide connected with this novel lytic peptide and assessed the cytotoxic
      activity in vitro and in vivo. METHODS: In vitro: We assessed the cytotoxicity of
      TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity
      for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In
      addition, we performed analysis of confocal fluorescence microscopy and apoptosis
      assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the
      change in mitochondria membrane potential. In vivo: TfR-lytic was administered
      intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks
      tumor sections were histologically analyzed. RESULTS: The TfR-lytic hybrid
      peptide showed cytotoxic activity in 12 cancer cell lines, with IC(50) values as
      low as 4.0-9.3 MUM. Normal cells were less sensitive to this molecule, with
      IC(50) values > 50 MUM. Competition assay using TfR antibody and knockdown of
      this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide.
      In addition, it was revealed that this molecule can disintegrate the cell
      membrane of T47D cancer cells just in 10 min, to effectively kill these cells and
      induce approximately 80% apoptotic cell death but not in normal cells. The
      intravenous administration of TfR-lytic peptide in the athymic mice model
      significantly inhibited tumor progression. CONCLUSIONS: TfR-lytic peptide might
      provide a potent and selective anticancer therapy for patients.

PMID- 21849093
TI  - Religiosity and resilience in persons at high risk for major depression.
AB  - BACKGROUND: Few studies have examined religiosity as a protective factor using a
      longitudinal design to predict resilience in persons at high risk for major
      depressive disorder (MDD). METHOD: High-risk offspring selected for having a
      depressed parent and control offspring of non-depressed parents were evaluated
      for psychiatric disorders in childhood/adolescence and at 10-year and 20-year
      follow-ups. Religious/spiritual importance, services attendance and negative life
      events (NLEs) were assessed at the 10-year follow-up. Models tested differences
      in relationships between religiosity/spirituality and subsequent disorders among
      offspring based on parent depression status, history of prior MDD and level of
      NLE exposure. Resilience was defined as lower odds for disorders with greater
      religiosity/spirituality in higher-risk versus lower-risk offspring. RESULTS:
      Increased attendance was associated with significantly reduced odds for mood
      disorder (by 43%) and any psychiatric disorder (by 53%) in all offspring;
      however, odds were significantly lower in offspring of non-depressed parents than
      in offspring of depressed parents. In analyses confined to offspring of depressed
      parents, those with high and those with average/low NLE exposure were compared:
      increased attendance was associated with significantly reduced odds for MDD, mood
      disorder and any psychiatric disorder (by 76, 69 and 64% respectively) and
      increased importance was associated with significantly reduced odds for mood
      disorder (by 74%) only in offspring of depressed parents with high NLE exposure.
      Moreover, those associations differed significantly between offspring of
      depressed parents with high NLE exposure and offspring of depressed parents with
      average/low NLE exposure. CONCLUSIONS: Greater religiosity may contribute to
      development of resilience in certain high-risk individuals.

PMID- 21849094
TI  - Benefits of whole ginger extract in prostate cancer.
AB  - It is appreciated far and wide that increased and regular consumption of fruits
      and vegetables is linked with noteworthy anticancer benefits. Extensively
      consumed as a spice in foods and beverages worldwide, ginger (Zingiber officinale
      Roscoe) is an excellent source of several bioactive phenolics, including non
      volatile pungent compounds such as gingerols, paradols, shogaols and gingerones.
      Ginger has been known to display anti-inflammatory, antioxidant and
      antiproliferative activities, indicating its promising role as a chemopreventive
      agent. Here, we show that whole ginger extract (GE) exerts significant growth
      inhibitory and death-inductory effects in a spectrum of prostate cancer cells.
      Comprehensive studies have confirmed that GE perturbed cell-cycle progression,
      impaired reproductive capacity, modulated cell-cycle and apoptosis regulatory
      molecules and induced a caspase-driven, mitochondrially mediated apoptosis in
      human prostate cancer cells. Remarkably, daily oral feeding of 100 mg/kg body
      weight of GE inhibited growth and progression of PC-3 xenografts by approximately
      56 % in nude mice, as shown by measurements of tumour volume. Tumour tissue from
      GE-treated mice showed reduced proliferation index and widespread apoptosis
      compared with controls, as determined by immunoblotting and immunohistochemical
      methods. Most importantly, GE did not exert any detectable toxicity in normal,
      rapidly dividing tissues such as gut and bone marrow. To the best of our
      knowledge, this is the first report to demonstrate the in vitro and in vivo
      anticancer activity of whole GE for the management of prostate cancer.

PMID- 21849095
TI  - Role of environmental poliovirus surveillance in global polio eradication and
      beyond.
AB  - Environmental poliovirus surveillance (ENV) means monitoring of poliovirus (PV)
      transmission in human populations by examining environmental specimens supposedly
      contaminated by human faeces. The rationale is based on the fact that PV-infected
      individuals, whether presenting with disease symptoms or not, shed large amounts
      of PV in the faeces for several weeks. As the morbidity:infection ratio of PV
      infection is very low, this fact contributes to the sensitivity of ENV which
      under optimal conditions can be better than that of the standard acute flaccid
      paralysis (AFP) surveillance. The World Health Organization has included ENV in
      the new Strategic Plan of the Global Polio Eradication Initiative for years 2010
      2012 to be increasingly used in PV surveillance, supplementing AFP surveillance.
      In this paper we review the feasibility of using ENV to monitor wild PV and
      vaccine-derived PV circulation in human populations, based on global experiences
      in defined epidemiological situations.

PMID- 21849096
TI  - Herpes zoster in Australia.

PMID- 21849097
TI  - Risk factors for Salmonella prevalence in laying-hen farms in Japan.
AB  - Human salmonellosis cases, particularly those caused by Salmonella Enteritidis,
      have been closely linked to egg consumption. This epidemiological survey was
      conducted to determine the baseline Salmonella prevalence and identify the risk
      factors for Salmonella prevalence in laying-hen farms in Japan. Caecal excrement
      samples and dust samples were obtained from 400 flocks in 338 laying-hen farms.
      Salmonella was identified in 20.7% of the farms and 19.5% of the flocks. The
      prevalence of Salmonella was significantly higher in flocks reared in windowless
      houses than in those reared in open houses. In addition, the risk of Salmonella
      presence was significantly higher when the windowless house farms implemented
      induced moulting or in-line egg processing. Efforts to reduce human salmonellosis
      in Japan should continue to focus on the establishment of control measures in
      laying-hen farms, especially those with windowless houses implementing induced
      moulting and equipped with in-line egg processing.

PMID- 21849098
TI  - Reduced spillover transmission of Mycobacterium bovis to feral pigs (Sus scofa)
      following population control of brushtail possums (Trichosurus vulpecula).
AB  - In New Zealand, bovine tuberculosis (bTB) is present in domestic cattle and deer
      herds primarily as the result of on-going disease transmission from the primary
      wildlife host, the brushtail possum (Trichosurus vulpecula). However, bTB is also
      present in other introduced free-ranging mammalian species. Between 1996 and
      2007, we conducted a series of studies to determine whether poison control of
      possum populations would have any effect on the prevalence of Mycobacterium bovis
      infection in sympatric feral pigs (Sus scrofa). We compared trends in the
      prevalence of bTB infection in feral pigs in six study areas: possum numbers were
      reduced in three areas, but not in the other three, effectively providing a
      thrice-replicated before-after-control-intervention design. Before possum
      control, the overall prevalence of culture-confirmed M. bovis infection in feral
      pigs was 16.7-94.4%, depending on area. Infection prevalence varied little
      between genders but did vary with age, increasing during the first 2-3 years of
      life but then declining in older pigs. In the areas in which possum control was
      applied, M. bovis prevalence in feral pigs fell to near zero within 2-3 years,
      provided control was applied successfully at the whole-landscape scale. In
      contrast, prevalence changed much less or not at all in the areas with no possum
      control. We conclude that feral pigs in New Zealand acquire M. bovis infection
      mainly by inter-species transmission from possums, but then rarely pass the
      disease on to other pigs and are end hosts. This is in contrast to the purported
      role of pigs as bTB maintenance hosts in other countries, and we suggest the
      difference in host status may reflect differences in the relative importance of
      the oral route of infection in different environments. Despite harbouring M.
      bovis infection for a number of years, pigs in New Zealand do not sustain bTB
      independently, but are good sentinels for disease prevalence in possum
      populations.

PMID- 21849099
TI  - Use of the self-controlled case-series method in vaccine safety studies: review
      and recommendations for best practice.
AB  - The self-controlled case-series method was originally developed to investigate
      potential associations between vaccines and adverse events, and is now commonly
      used for this purpose. This study reviews applications of the method to vaccine
      safety investigations in the period 1995-2010. In total, 40 studies were
      reviewed. The application of the self-controlled case-series method in these
      studies is critically examined, with particular reference to the definition of
      observation and risk periods, control of confounders, assumptions and potential
      biases, methodological and presentation issues, power and sample size, and
      software. Comparisons with other study designs undertaken in the papers reviewed
      are also highlighted. Some recommendations are presented, with the emphasis on
      promoting good practice.

PMID- 21849100
TI  - Fear of Alzheimer's disease in the French population: impact of age and proximity
      to the disease.
AB  - BACKGROUND: The negative image of Alzheimer's disease (AD) in our society has a
      substantial impact on treating, caring for and integrating those suffering from
      the disease and their relatives. Little research has been conducted on social
      perception of AD in the community. METHODS: The aim of this study was to
      investigate the perception, knowledge, opinions and beliefs about AD in the
      French population. A cross-sectional telephone survey of 2013 randomly selected
      community-dwelling people aged 18 years and over was conducted. Multivariate
      logistic regressions were used for identifying predictors of the personal fear of
      developing AD, both for the global sample and for different age groups. RESULTS:
      Sixty percent of the sample reported personal fear of developing AD. This
      attitude was strongly related to age, becoming predominant among the elderly. In
      the middle-aged group, personal fear of developing AD was highest in women with
      poor self-perceived health and, in particular, those who cared for someone with
      AD. Being a caregiver or knowing someone with the disease was also strongly
      associated with fear among younger adults aged 18-34. CONCLUSIONS: These results
      serve as an incentive for developing special education and prevention programs
      focused on different age groups and caregivers of AD.

PMID- 21849101
TI  - Are old people so gentle? Functional and dysfunctional impulsivity in the
      elderly.
AB  - BACKGROUND: Although old people may seem less impulsive than adults, numerous
      experimental studies report that they have inhibitory deficits. Bearing in mind
      that there is a relationship between inhibition processes and impulsivity, age
      related inhibition deficits suggest that older people could be more impulsive
      than adults. METHODS: The aim of the current study was to compare the functional
      and dysfunctional impulsivity scores obtained in a sample of elderly people (65
      years old and above) with those obtained in previous studies on samples of
      adolescents and adults. Dickman's Impulsivity Inventory was administered to 190
      individuals aged between 65 and 94 years without dementia or cognitive
      impairment. RESULTS: Results indicated that the elderly sample showed higher
      dysfunctional impulsivity levels than the adult samples, which is consistent with
      the inhibition deficits mentioned above. There were no significant differences in
      functional impulsivity. Furthermore, old women had higher scores than old men on
      dysfunctional impulsivity. CONCLUSIONS: This study provides evidence of age
      related changes in dysfunctional impulsivity. Functional impulsivity did not show
      the same pattern as dysfunctional impulsivity, being quite stable across the age
      span. it seems, then, that impulsivity cannot be considered to decrease with age
      and dysfunctional impulsivity may even increase.

PMID- 21849102
TI  - Acquisition of generic noun phrases in Chinese: learning about lions without an '
      s'.
AB  - English-speaking children understand and produce generic expressions in the
      preschool years, but there are cross-linguistic differences in how generics are
      expressed. Three studies examined interpretation of generic noun phrases in three
      to seven-year-old child (N=192) and adult speakers (N=163) of Mandarin Chinese.
      Contrary to suggestions by Bloom (1981), Chinese-speaking adults honor a clear
      distinction between generics (expressed as bare NPs) and other quantified
      expressions ('all'/suo3you3 and 'some'/you3de). Furthermore, Mandarin-speaking
      children begin to distinguish generics from 'all' or 'some' as early as five
      years, as shown in both confirmation (Study 2) and property-generation (Study 3)
      tasks. Nonetheless, the developmental trajectory for Chinese appears prolonged
      relative to English and this seems to reflect difficulty with 'all' and 'some'
      rather than difficulty with generics. Altogether these results suggest that
      generics are primary, and that the consistency of markings affects the rate at
      which non-generic NPs are distinguished from generics.

PMID- 21849103
TI  - The shape-bias in Spanish-speaking children and its relationship to vocabulary.
AB  - Considerable research has demonstrated that English-speaking children extend
      nouns on the basis of shape. Here we asked whether the development of this bias
      is influenced by the structure of a child's primary language. We tested English-
      and Spanish-speaking children between the ages of 1 ; 10 and 3 ; 4 in a novel
      noun generalization task. Results showed that English learners demonstrated a
      robust shape-bias, whereas Spanish learners did not. Further, English-speaking
      children produced more shape-based nouns outside the laboratory than Spanish
      speaking children, despite similar productive vocabulary sizes. We interpret the
      results as evidence that attentional biases arise from the specifics of the
      language environment.

PMID- 21849104
TI  - Factors contributing to child scrambling: evidence from Ukrainian.
AB  - This study examines the word order phenomenon of optional scrambling in
      Ukrainian. It aims to test factors such as semantic features and object type that
      have been shown to affect scrambling in other languages. Forty-one children
      between 2 ; 7 and 6 ; 0, and twenty adult speakers participated in an elicited
      production experiment. The picture description task was used to set appropriate
      semantic contexts to prompt the production of scrambled structures. The results
      demonstrate that the children scrambled at higher rates in definite/partitive
      contexts than in indefinite/non-specific contexts. This suggests that children
      are susceptible to the same semantic features that are associated with NP
      scrambling in adult production. However, they differ from adults in pronominal
      scrambling and approximate adult scrambling behaviour only around four to five
      years. These findings underline the complex nature of syntax/semantics/phonology
      correlation in scrambling, and contribute to our understanding of the issue of
      optionality in child and adult grammar.

PMID- 21849105
TI  - Improving pregnancy outcome in obese women.
AB  - The global pandemic of maternal obesity presents a major challenge for healthcare
      providers, and has significant short- and long-term implications for both
      maternal and fetal health. Currently, the evidence-base underpinning many of the
      interventions either currently in use or recommended to improve pregnancy outcome
      in obese women is limited. The nature and timing of these interventions vary
      widely, ranging from simple advice to more intensive dietary and exercise
      programmes, cognitive behavioural therapy and drug trials. In addition, a growing
      number of very severely obese women now enter pregnancy having had surgical
      interventions. Although surgical interventions such as gastric bypass or banding
      may be associated with improved pregnancy outcomes, these women have particular
      nutritional requirements, which need to be addressed to optimise pregnancy
      outcome. Until the outcomes of ongoing current trials are reported and provide a
      firm evidence base on which to base future intervention strategies and guide
      evidence based care for obese pregnant women, pregnancy outcome is best optimised
      by high-risk antenatal care delivered by healthcare providers who are experienced
      in supporting these high-risk women.

PMID- 21849106
TI  - Vitamin D and immune function: an overview.
AB  - Immunomodulatory actions of vitamin D have been recognised for over a quarter of
      a century, but it is only in the last few years that the significance of this to
      normal human physiology has become apparent. Two key factors have underpinned
      this revised perspective. Firstly, there are increasing data linking vitamin
      insufficiency with prevalent immune disorders. Improved awareness of low
      circulating levels of precursor 25-hydroxyvitamin D in populations across the
      globe has prompted epidemiological investigations of health problems associated
      with vitamin D insufficiency. Prominent among these are autoimmune diseases such
      as multiple sclerosis, type 1 diabetes and Crohn's disease, but more recent
      studies indicate that infections such as tuberculosis may also be linked to low
      25-hydroxyvitamin D levels. The second factor expanding the link between vitamin
      D and the immune system is our improved knowledge of the mechanisms that
      facilitate this association. It is now clear that cells from the immune system
      contain all the machinery needed to convert 25-hydroxyvitamin D to active 1,25
      dihydroxyvitamin D, and for subsequent responses to 1,25-dihydroxyvitamin D.
      Mechanisms such as this are important for promoting antimicrobial responses to
      pathogens in macrophages, and for regulating the maturation of antigen-presenting
      dendritic cells. The latter may be a key pathway by which vitamin D controls T
      lymphocyte (T-cell) function. However, T-cells also exhibit direct responses to
      1,25-dihydroxyvitamin D, notably the development of suppressor regulatory T
      cells. Collectively these observations suggest that vitamin D is a key factor
      linking innate and adaptive immunity, and both of these functions may be
      compromised under conditions of vitamin D insufficiency.

PMID- 21849107
TI  - [Site-directed mutagenesis and protein expression of KCNQ2 gene associated with
      neonatal convulsions].
AB  - OBJECTIVE: To study the protocol of construction of a KCNQ2-c.812G>T mutant and
      it's eukaryotic expression vector, the c.812G>T (p.G271V) mutation which was
      detected in a Chinese pedigree of benign familial infantile convulsions, and to
      examine the expression of mutant protein in human embyonic kidney (HEK) 293
      cells. METHODS: A KCNQ2 mutation c.812G>T was engineered on KCNQ2 cDNAs cloned
      into pcDNA3.0 by sequence overlap extension PCR and restriction enzymes. HEK293
      cells were co-transfected with pRK5-GFP and KCNQ2 plasmid (the wild type or
      mutant) using lipofectamine and then subjected to confocal microscopy. The
      transfected cells were immunostained to visualize the intracellular expression of
      the mutant molecules. RESULTS: Direct sequence analysis revealed a G to T
      transition at position 812. The c.812G>T mutation was correctly combined to
      eukaryotic expressive vector pcDNA3.0 and expressed in HEK293 cells.
      Immunostaining of transfected cells showed the expression of both the wild type
      and mutant molecules on the plasma membrane, which suggested that the c.812G>T
      mutation at the pore forming region of KCNQ2 channel did not impair normal
      protein expression in HEK293 cells. CONCLUSIONS: Successful construction of
      mutant KCNQ2 eukaryotic expression vector and expression of KCNQ2 protein in
      HEK293 cells provide a basis for further study on the functional effects of
      convulsion-causing KCNQ2 mutations and for understanding the molecular
      pathogenesis of epilepsy.

PMID- 21849108
TI  - [Relationship between viral burden in urine and hearing loss in neonates with
      cytomegalovirus infection].
AB  - OBJECTIVE: To determine the relationship between viral burden in urine and
      hearing loss in neonates with cytomegalovirus (CMV) infection. METHODS: Twenty
      two neonates with CMV infection between April 2006 and January 2010 were
      enrolled. Their viral burden in urine and hearing loss information were studied.
      The receiver operating characteristic curve (ROC) was constructed and the cutoff
      was determined based on their medical information. The hearing levels were
      evaluated by brain stem auditory evoked potential (BAEP) during the age of 3 to 6
      months in 20 patients. RESULTS: The viral burden in urine in neonates with
      abnormal BAEP was higher than that in neonates with normal BAEP (5.06 +/- 1.50 vs
      3.73 +/- 0.86, P<0.05). Hearing loss was predicted with a sensitivity of 0.545
      and a specificity of 1.0 by using ROC at the cutoff point of 5.1 which were
      defined after logarithmic conversion at 1.27*10(5) copies/mL of CMV burden in
      urine. The incidence of hearing loss during the age of 3 to 6 months was
      strikingly higher in high viral burden group than that in low viral load group
      (P<0.05). CONCLUSIONS: The viral burden in urine can predict the possibility of
      hearing loss in neonates with CMV infection. Hearing loss is likely to be
      developed when viral burden in urine >=1.27*10(5) copies/mL in neonates with CMV
      infection.

PMID- 21849109
TI  - [Value of MRI in the diagnosis of cerebral abscess caused by Candida albicans in
      premature infants].
AB  - OBJECTIVE: To explore the value of serial magnetic resonance imaging (MRI) in the
      diagnosis of cerebral abscess caused by Candida albicans in premature infants.
      METHODS: The clinical data of 8 premature infants with central nervous system
      invasive fungal infection (IFI) were retrospectively studied. The infants
      underwent serial cerebral MRI scans (T1WI, T2WI and DWI). RESULTS: Candida
      albicans was found as pathogen in all of the 8 infants. Seven infants presented
      with cerebral abscess and 4 infants had concurrent meningitis. Widespread
      involvements were found on MRI, particular in white matter area of subcortex,
      centrum semiovale and periventricle. The MR imaging findings in 4 infants within
      11 days after IFI showed diffusive and multiple miliary nodes and hyperintense
      signals on DWI, but obvious changes were not found on T1WI and T2WI. The most
      striking hyperintense signals on T1WI and hypointense signals on T2WI appeared
      between 2 and 4 weeks after IFI, and some nodes of rim-like hyperintensity and
      marked contrast enhancement were also noted on T1WI. Smaller and smaller changes
      of the miliary foci were seen on T1WI and T2WI 4 weeks later. Delayed myelination
      and thinner corpus callous were shown in 2 patients at three months. CONCLUSIONS:
      MRI-DWI and serial MRIs are helpful in the early diagnosis of candida cerebral
      abscess and the evaluation of treatment outcome in premature infants.

PMID- 21849110
TI  - [Clinical features of feeding intolerance in preterm infants].
AB  - OBJECTIVE: To study the clinical features of feeding intolerance in preterm
      infants in order to provide clinical evidence for preventing feeding intolerance.
      METHODS: A total of 716 preterm infants hospitalized in the First Affiliated
      Hospital of Xinjiang Medical University between January 2007 and December 2009
      were enrolled. The clinical data of the infants were retrospectively studied.
      RESULTS: Feeding intolerance occurred in 197 (27.5%) out of 716 infants, with an
      incidence of 76.4% in the very low birth weight infants. Simple gastric retention
      (47.2%) was found as the most common clinical manifestation. Feeding intolerance
      usually occurred within 3 days after feeding. Compared with the preterm infants
      with feeding success, the preterm infants with feeding intolerance showed lower
      gestational age and birth weight, more delayed feeding and higher rate of
      asphyxia and respiratory diseases (P<0.05). There were no significant differences
      in the gender, maternal age, ethnic group, delivery way and the incidence of
      fetal distress between the two groups. With increasing gestational age,
      increasing birth weight, early feeding, the incidence of feeding intolerance in
      preterm infants was reduced. CONCLUSIONS: The low gestational age, low birth
      weight, delayed feeding and complications may be associated with the development
      of feeding intolerance in preterm infants.

PMID- 21849111
TI  - [Efficacy of thalidomide for treatment of juvenile idiopathic arthritis].
AB  - OBJECTIVE: To evaluate the efficacy of thalidomide in the treatment of juvenile
      idiopathic arthritis (JIA). METHODS: Twelve children with JIA who did not respond
      to conventional treatment were administered with thalidomide (2 mg/kg daily). The
      symptoms, signs, and laboratory test results were compared before and after
      treatment. The thalidomide-related side effects were observed. RESULTS: The
      average dosage of prednisone was reduced from 1.92 +/- 0.16 mg/kg*d to 0.49 +/-
      0.42 mg/kg*d in the 12 patients 6 months after thalidomide treatment (P<0.01).
      Four patients did not need prednisone treatment any more. White blood cell count,
      erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and serum ferritin
      (SF) significantly decreased after treatment in all of 12 patients (P<0.01).
      Hemoglobin level increased to normal in 8 patients after treatment (P<0.01). The
      number of affected joints decreased from 5 before treatment to zero to 2 after
      treatment in patients with polyarticular JIA (P<0.01). Signs of hip involvement
      and Schober's sign turned negative in enthesitis-related cases. No thalidomide
      related side effects were observed. CONCLUSIONS: Thalidomide is effective in the
      treatment of JIA in children who do not respond to conventional treatment.

PMID- 21849112
TI  - [Comparisons of epidemiological and clinical characteristics in children with
      hand-foot-mouth disease caused by Enterovirus 71 and Coxackievirus A16].
AB  - OBJECTIVE: To compare the differences of epidemiological and clinical
      characteristics in children with hand-foot-mouth disease (HFMD) caused by
      Coxsackievirus A16 (CA16) and Enterovirus 71 (EV71). METHODS: The samples of
      vesicle fluid and throat swabs of 108 children with HFMD were collected and
      detected for enterovirus by RT-PCR. The clinical data of children with EV71 and
      CA16 infection were retrospectively reviewed and compared. RESULTS: The total
      positive rate of enterovirus was 97.2% (105/108). Of the 105 cases, 56 cases were
      positive for EV71 (51.9%), 39 cases were positive for CA16 (36.1%), 2 cases were
      positive for other enterovirus (1.9%), and 8 cases were co-infected by EV71 and
      CA16 (7.4%). There were no significant differences in age and sex between EV71
      and CV16 infected cases. The univariate analysis showed that the incidences of
      herpes of mouth, erythra of knees, and nose running in children infected by CA16
      were higher than in those infected by EV71. The multivariate logistic regression
      analysis showed that the HFMD children who had erythra of knees had higher
      probability of CA16 infection. CONCLUSIONS: EV71 should be considered as the
      pathogen in children with HFMD who have no herpes of mouth, erythra of knees, and
      nose running.

PMID- 21849113
TI  - [Treatment of Kawasaki disease by different doses of immunoglobulin: a Mata
      analysis of therapeutic effects].
AB  - OBJECTIVE: To assess the therapeutic effects and safety of different doses of
      immunoglobulin in the treatment of Kawasaki disease. METHODS: The papers related
      to the treatment of Kawasaki disease were electronically searched in the
      databases of PubMed, EMBASE, Cochrane Library, CNKI, VIP and Wanfang. Randomized
      clinical trials (RCT) on the treatment of Kawasaki disease with different doses
      of immunoglobulin were included and assessed for quality. A Mata analysis was
      performed by RevMan 5.0. RESULTS: Twenty-eight RCTs involved 2596 cases were
      included. The results of Meta analysis showed that there were no significant
      differences in the incidences of coronary artery injuries at various phases,
      adverse effects and fever disappearance time between the immunoglobulin treatment
      groups at the doses of 1 g/(kg*d) for 1-2 days and 2 g/(kg*d) for single use. The
      fever disappearance time in the immunoglobulin treatment group at the dose of 1
      g/(kg*d) for 1-2 days was significantly shorter than that in the immunoglobulin
      treatment group at the dose of 400 mg/(kg*d) for 4-5 days, but there were no
      significant differences in the incidences of coronary artery injuries at the
      acute phase and 6 months after treatment and adverse effects between the two
      groups. The incidence of coronary artery injuries at the acute phase and 6 months
      was lower and the fever disappearance time was shorter in the immunoglobulin
      treatment group at the dose of 2 g/(kg*d) for single use than those in the
      immunoglobulin treatment group at the dose of 400 mg/(kg*d) for 4-5 days, but
      there were no significant differences in the incidences of coronary artery
      injuries at the subacute phase and 12 months after treatment and adverse effects
      between the two groups. CONCLUSIONS: There are similar therapeutic effects for
      Kawasaki disease between the immunoglobulin treatment groups at the doses of 1
      g/(kg*d) for 1-2 days and 2 g/(kg*d) for single use. The fever disappearance time
      in the two groups is shorter than that in the treatment group at the dose of 400
      mg /(kg*d) for 4-5 days.

PMID- 21849114
TI  - [Influencing factors of mother-infant vertical transmission of hepatitis B
      virus].
AB  - OBJECTIVE: To study the factors influencing mother-infant vertical transmission
      of hepatitis B virus (HBV). METHODS: A total of 635 pregnant women with chronic
      hepatitis B or chronic asymptomatic HBV carriers were enrolled. The rate of HBV
      infection was compared between the infants born from the pregnant women of
      different HBV-DNA load, different ways of delivery and different liver functions
      at birth and 3 months after birth. The newborn infants were routinely injected
      with hepatitis B immunoglobulin (200 IU) and hepatitis B vaccine (10 MUg) within
      12 hrs of birth. The newborns presenting HBV infection within 24 hrs of birth by
      serum test were re-injected with hepatitis B immunoglobulin (200 IU) 14 days
      after birth. RESULTS: The rate of HBV infection in infants with maternal HBV-DNA
      load >10(5) copies/mL was higher than in those with maternal HBV-DNA load <=
      10(5) copies/mL at birth (14.4% vs 4.1%; P<0.01) and 3 months after birth (4.7%
      vs 0; P<0.01).The rate of HBV infection at 3 months was lower than at birth in
      both groups. The rate of HBV infection in infants born by natural labor was
      higher than in those born by caesarean birth at birth (P<0.05), however, by 3
      months after birth, the rate of HBV infection between the two groups was similar.
      The rate of HBV infection was higher in infants born to chronic asymptomatic HBV
      carrier mothers than that in infants born to chronic hepatitis B mothers at birth
      (P<0.01), but there were no significant differences in the two groups 3 months
      later. CONCLUSIONS: The maternal HBV-DNA load is correlated with the rate of HBV
      infection of infants. It might thus be an effective way to reduce the rate of HBV
      infection in infants by decreasing maternal HBV-DNA load. With the administration
      of hepatitis B immunoglobulin and hepatitis B vaccine, the delivery way and the
      liver function of pregnant women may not to be factors influencing mother-infant
      HBV vertical transmission.

PMID- 21849115
TI  - [Studies of electromyography and genetics in children with Charcot-Marie-Tooth
      disease type 1].
AB  - OBJECTIVE: To study the electromyographic and genetic characteristics in children
      with Charcot-Marie-Tooth disease type 1 (CMT1). METHODS: Routine electromyography
      and nerve conduction were performed in 24 children with CMT1. Polymerase chain
      reaction (PCR) combined with restriction enzyme digestion was used to detect gene
      duplication on chromosome 17p11.2-12. Ten healthy children served as the control
      group. RESULTS: The peripheral nerve conduction velocity slowed or disappeared in
      all of the 24 patients (100%). The lesions of the sensory nerves were more severe
      than the motor nerves, and the lesions of the lower limbs were more severe than
      the upper limbs. Of 72 muscles detected, 40 (56%) showed neurogenic lesions. The
      older the patients, the more severe the muscle lesions. Specific junction
      fragments (1760 bp) were identified in 13 (54%) out of 24 patients, but were not
      identified in the healthy controls. CONCLUSIONS: The electromyographic changes
      are characterized by peripheral nerve conduction velocities slowing and
      neurogenic lesions of muscles in children with CMT1. The PCR combined with
      restriction enzyme digestion may be a simple and accurate method for gene
      diagnosis of CMT1.

PMID- 21849116
TI  - [Chromosome analysis in 92 children with congenital mental retardation].
AB  - OBJECTIVE: To explore the chromosome karyotypes in children with mental
      retardation. METHODS: The peripheral blood lymphocytes from 92 children with
      congenital mental retardation were cultured and analysed by the G-band technique.
      RESULTS: Of the 92 cases, 43 cases (47%) showed chromosome abnormalities.
      Autosomal abnormalities were found in 35 cases (38%) and sex chromosome
      abnormalities were found in 8 cases (9%). A novel abnormal karyotype 45, XX, psu
      dic (11;9) (p15;p24) was found in a child. CONCLUSIONS: Chromosome abnormalities
      may be important cytogenetic factors for congenital mental retardation.
      Cytogenetic chromosome karyotypic analysis appears to be an important method for
      genetic screening of congenital mental retardation.

PMID- 21849117
TI  - [Heart rate variability in children with beta-thalassemia major].
AB  - OBJECTIVE: To study the diagnostic value of heart rate variability (HRV) in heart
      dysfunction in children with beta-thalassemia major (beta-TM)by examining the
      changes of HRV in beta-TM children. METHODS: A 24 hours Holter monitoring
      electrocardiogram (Holter) was performed in 21 children with beta-TM and 15
      healthy children (control group). The time domain and frequency domain indexes of
      HRV in the two groups were compared. The correlation between serum ferritin
      levels and HRV was evaluated. RESULTS: The time domain indexes SDNN, rMSSD and
      PNN50 and the frequency domain indexes very low frequency (VLF), low frequency
      (LF) and high frequency (HF) in the beta-TM group were significantly lower than
      in the control group (P<0.05). There was no correlation between serum ferritin
      level and HRV in children with beta-TM. CONCLUSIONS: The autonomic nerve
      dysfunction exists in children with beta-TM. HRV analysis is useful in the
      prediction of early cardiac dysfunction in children with beta-TM.

PMID- 21849118
TI  - [Childhood rhabdomyosarcoma: a retrospective review of 23 cases].
AB  - OBJECTIVE: To study the clinical characteristics, treatment and outcome of
      childhood rhabdomyosarcoma. METHODS: The clinical data of 23 children with
      rhabdomyosarcoma from January, 1998 to October, 2008 were retrospectively
      reviewed. RESULTS: Of the 23 cases, 15 were male and 8 were female, with a mean
      age of 5 years old (7 months to 12 years old). Based on the American IRS staging
      system, 2 cases were in stage I, 4 cases in stage II, 8 cases in stage III, and 9
      were in stage IV. The primary sites were found in head and neck (14 cases),
      extremities (4 cases), bladder (2 cases), kidney (1 case), post-peritoneum (1
      case) and bile duct (1 case). All of the children were confirmed with
      rhabdomyosarcoma by biopsy and immunohistochemistry. The clinical manifestations
      were related to the tumor tissues-induced space occupying, compression and
      erosion and were aspecific. The patients in different IRS stages were given
      different treatment regimens. The chemotherapy regimens VDCA, VAC or VadrC were
      used before 2002. After 2002, the Children's Oncology Group (COG) protocol was
      employed. The two-year survival rate was 63% in 19 patients who received a
      combination of surgery, chemotherapy and radiotherapy, but none of 4 patients who
      received a surgery alone or a combination of surgery and chemotherapy or
      radiotherapy survived more than two years. CONCLUSIONS: The clinical
      manifestations of childhood rhabdomyosarcoma are not specific. A combination
      therapy including surgery, chemotherapy and radiation is effective to the
      improvement of the survival rate in children with rhabdomyosarcoma.

PMID- 21849119
TI  - [Relationship between the regulation of intestinal NF-kappaB and TNF-alpha by
      glutamine and the protective effects of glutamine against intestinal injury].
AB  - OBJECTIVE: To study whether the protective effects of glutamine against
      intestinal injury are associated with the regulation of intestinal secretion of
      NF-kappaB and TNF-alpha by glutamine. METHODS: Twenty-four 10-day-old Wistar rat
      pups were randomly intraperitoneally injected with normal sodium of 1 mL/kg
      (control group; n=8), LPS of 5 mg/kg (endotoxemia group; n=8) or LPS of 5 mg/kg
      plus glutamine of 10 mL/kg (glutamine group; n=8). The rats were sacrificed 3 hrs
      after injection. A segment of distal ileum was dissected. The pathologic changes
      of the small intestine were observed under an optical microscope (hematoxylin
      eosin staining). The expression of intestinal NF-kappaB mRNA and protein were
      detected by RT-PCR and Western blot respectively. The TNF-alpha level in
      intestinal tissues was measured using ELISA. RESULTS: The structure of the small
      intestine in the control group remained normal. The inflammation cells
      infiltration and the edema of interstitial substance and epithelials were
      observed in the endotoxemia and glutamine groups. The pathologic changes in the
      glutamine group were significantly alleviated when compared with the endotoxemia
      group. The expression of NF-kappaB mRNA and protein in the glutamine group was
      significantly lower than that in the endotoxemia group (P<0.01). The secretion of
      TNF-alpha in the glutamine group was significantly lower than that in the
      endotoxemia group (P<0.01). CONCLUSIONS: The protective effects of glutamine
      against intestinal injury may be associated with the down-regulation of
      intestinal NF-kappaB mRNA and protein expression and the reduction of the
      secretion of TNF-alpha.

PMID- 21849120
TI  - [Effects of baicalin on apoptosis in rats with autoimmune encephalomyelitis].
AB  - OBJECTIVE: To study the therapeutic efficacy of baicalin and its effect on
      apoptosis of inflammatory cells in spinal cords in Wistar rats with autoimmune
      encephalomyelitis (EAE). METHODS: Forty-four rats were randomly divided into four
      groups: normal control group (control, n=10), EAE group (n=12), and two
      intervention groups with dexamethasone (DXM) or baicalin. Seven days after
      immunization, the two intervention groups were injected intraperitoneally with
      DXM (1 mg/kg) and baicalin (200 mg/kg) for 1 week, respectively. The spinal cords
      were removed 14 days after immunization, and stained with hematoxylin and eosin.
      MBP expression in spinal cords was detected by immunohistochemistry. The
      apoptosis of inflammatory cells in spinal cords was detected by TUNEL. RESULTS:
      The weight gain rate in the untreated EAE and the DXM or baicalin intervention
      groups were significantly lower than that in the control group (P<0.05). The
      weight gain rate in the baicalin intervention group was significantly higher than
      that in the untreated EAE and the DXM intervention groups (P<0.05). The scores of
      neurological function in the two intervention groups were significantly higher
      than that in the untreated EAE group (P<0.05). DXM or baicalin treatment
      significantly increased the MBP expression compared with the untreated EAE group
      (P<0.05). The apoptosis of inflammatory cells increased more in the DXM and the
      baicalin intervention groups compared with the untreated EAE groups (P<0.05).
      CONCLUSIONS: Baicalin has protective effects against EAE in rats. It can promote
      the apoptosis of inflammatory cells in spinal cords.

PMID- 21849121
TI  - [Expression of matrix metalloproteinase-9 in myocardium of mice with viral
      myocarditis].
AB  - OBJECTIVE: To investigate the dynamic changes of expression of matrix
      metalloproteinases-9 in myocardium of mice with viral myocarditis (VMC) and its
      significance in the pathogenesis of viral myocarditis. METHODS: VMC model was
      prepared by an injection of CVB3 in BALB/C mice. The mice receiving an injection
      of culture solution without virus were used as the control group. Cardiac tissues
      were obtained 7, 14, 21 and 28 days after injection and made into paraffin
      sections. Myocardial histopathologic changes were observed by hematoxylin-eosin
      staining and Masson staining. The expression of MMP-9, type I collagen and type
      III collagen in cardiac tissues were quantified by SABC immunohistochemical
      method. RESULTS: The expression of MMP-9 in the VMC model group was observed on
      the 7th day, reached a peak on the 14th day, and was significantly higher than
      that in the control group at all time points (P<0.05). Compared with the control
      group, the expression of type I collagen in the VMC model group was up-regulated
      on the 21st day and reached a peak on the 28th day (P<0.05). The expression of
      type III collagen in the VMC model group was significantly higher than that in
      the control group on the 28th day (P<0.05). The expression of MMP-9 was
      positively correlated with myocardial histopathologic scores (r=0.832, P<0.05)
      and negatively correlated with type I collagen expression (r=-0.791, P<0.05).
      CONCLUSIONS: MMP-9 is over-expressed at the early stage in VMC mice, and
      participates in the pathological process of VMC through mediating the degradation
      metabolism of type I collagen. It may be an important factor that leads to
      myocardial collagen remodeling and myocardial fibrosis.

PMID- 21849122
TI  - [Deferoxamine induces apoptosis of K562 cells].
AB  - OBJECTIVE: To study the molecular mechanism of apoptosis of leukemic cells (K562
      cells) induced by iron chelating agent deferoxamine (DFO). METHODS: The
      exponentially growing K562 cells were used (1*10(6)/mL) in this study. The K562
      cells were treated with different concentrations of DFO (10, 50 and 100 mmol/L),
      DFO+FeCl3 (10 MUmol/L each) or normal saline (blank control). The cellular labile
      iron pool was measured with a fluorimetric assay using the metalsensitive probe
      calcein-AM. The viable count and cell viability were determined by typanblue
      assay. Cell apoptosis was determined by morphological study and flow cytometry
      assay. Caspase-3 activity in K562 cells was detected by colorimetry. RESULTS:
      After DFO treatment, the cellular labile iron pool and the viability of K562
      cells were reduced and the cell apoptosis increased in a time- and dose-dependent
      manner compared with the blank control group. The apoptosis rate of K562 cells in
      the DFO+FeCl3 treatment group was not significantly different from that in the
      blank control group. The caspase-3 activity in K562 cells increased significantly
      24 hrs after 50 and 100 MUmmol DFO treatment when compared with the blank control
      group (P<0.01). There was a negative correlation between cellular labile iron
      pool and caspase-3 activity of K562 cells (r=-0.894, P<0.05). CONCLUSIONS: DFO
      induces apoptosis of leukemic cells possibly through decreasing cellular labile
      iron pool and increasing caspase-3 activity of the cells.

PMID- 21849123
TI  - [Effect of myriocin on the expression of cyclinD1 in high glucose-induced
      hypertrophy mesangial cells].
AB  - OBJECTIVE: Myriocin (ISP-1) is a new type of immune inhibitor extracted from
      cordyceps sinensis. This study was to observe the effects of ISP-1 on the
      expression of cell cycle regulatory protein D1 (cyclinD1) in high glucose-induced
      hypertrophy rat glomerular mesangial cells (GMCs). METHODS: Rat GMCs were
      cultured in vitro and divided into three groups: high glucose (450 mg/dL D
      glucose), normal glucose (100 mg/dL D-glucose, control) and ISP-1 (450 mg/dL D
      glucose plus 100 MUg/mL ISP-1). The protein expression of cyclinD1 was detected
      by flow cytometry. RESULTS: The expression of cyclinD1 in GMCs in the high
      glucose group increased significantly in a time-dependent manner compared with
      that in the control group. ISP-1 treatment significantly inhibited the up
      regulated expression of cyclinD1 induced by high concentration glucose, and the
      expression of cyclinD1 was restored to the level of the control group 48 and 72
      hrs after ISP-1 treatment. CONCLUSIONS: High concentration of glucose can up
      regulate the expression of cyclinD1 in GMCs. ISP-1 may inhibit the up-regulated
      expression of cyclinD1, which might contribute to the protective effect of ISP-1
      against GMC hypertrophy induced by high glucose.

PMID- 21849124
TI  - [HIF-1alpha siRNA reduces retinal neovascularization in a mouse model of
      retinopathy of prematurity].
AB  - OBJECTIVE: To study the inhibition effect of HIF-1alpha specific siRNA expression
      vector pSUPERH1-siHIF-1alpha on retinal neovascularization in a mouse model of
      retinopathy of prematurity (ROP). METHODS: The mouse model of ROP was prepared by
      the method Smith described. Forty-eight ROP mice were randomly divided into two
      groups: an experimental group that was intravitreously injected with pSUPERH1
      siHIF-1alpha and a control group that was injected with pSUPER retro vector. The
      levels of HIF-1alpha and vascular endothelia growth factor (VEGF) in the retina
      were examined by Western blot. The retinal neovascularization was evaluated by
      angiography using FITC Dextran and quantitated histologically. RESULTS: The
      levels of HIF-1alpha and VEGF in the retina in the experimental group were
      reduced 90% and 65% respectively compared with those in the control group.
      Meanwhile, the number of retinal neovascular endothelial nucleus outbreaking the
      inner limit membrane in the experimental group was significantly reduced compared
      with that in the control group. CONCLUSIONS: The development of retinal
      neovascularization of ROP can be markedly inhibited by RNA interference targeting
      HIF-1alpha.

PMID- 21849125
TI  - [Clinical and pathological analysis of mesenchymal hamartoma of liver].

PMID- 21849126
TI  - [Clinical analysis of congenital heart disease complicated by other
      malformations].

PMID- 21849127
TI  - [A case report of incessant atrial tachycardia complicated by tachyarrhythmic
      cardiomyopathy].

PMID- 21849128
TI  - [Hand-foot-mouth disease complicated by brainstem encephalitis and cerebral edema
      in a neonate].

PMID- 21849129
TI  - [Late cerebral sequelae in prematurely born children].

PMID- 21849130
TI  - [Dose dispensing makes problems of the polypharmacy patient visible].

PMID- 21849131
TI  - [Medication errors after hospitalisation due to multi-dose drug dispensing in the
      primary sector].
AB  - Multi-dose drug dispensing (MDDD) was introduced in Denmark in 2001 in order to
      minimize medication errors. In May 2010 44.500 Danish citizens received MDDD. We
      report two cases where MDDD in the primary sector led to medication errors after
      hospitalisation, the reason partly being difficulties in getting information on
      MDDD on admission, lack of knowledge on handling MDDD in hospital and inadequate
      communication between the primary and the secondary sector. These problems has
      until now been underestimated.

PMID- 21849132
TI  - [Uncertain effects of health risk appraisals at worksites].
AB  - Health risk appraisals take place at Danish worksites even though the effects are
      unknown. The purpose of this article is to summarise international studies of
      health risk appraisals at worksites and identify the existing knowledge on the
      cost-effectiveness and effects on health. The studies show tendencies of small,
      but positive effects of health risk appraisals in combination with counselling on
      certain cardiovascular risk factors. It is, however, not possible to determine
      the economic effects of the efforts.

PMID- 21849133
TI  - [Diagnostic strategy of incidental findings of focal thyroid FDG uptake
      identified on PET/CT].
AB  - Incidental findings of focal fluorodeoxyglucose (FDG) uptake in the thyroid
      occurs more frequently with increased use of positron emission tomography (PET)
      with a frequency of 1-4% and a risk of cancer in the thyroid of > 30%. This
      article reviews the existing literature and recommends a diagnostic strategy to
      identify patients with high risk of thyroid malignancy. The diagnostic process
      should include measurement of thyroid function, thyroid scintigraphy and in
      patients with cold nodules detected by scintigraphy additional ultrasound guided
      fine-needle aspiration biopsy.

PMID- 21849134
TI  - [Treatment of placenta percreta requires a multidisciplinary approach].
AB  - Placenta percreta is a rare life-threatening obstetrical condition, often
      resulting in severe haemorrhage and hysterectomy. The incidence seems to be
      increasing, probably secondary to the increase in caesarean section rates. We
      present a protocol for an elective multidisciplinary approach with proactive
      management to reduce haemorrhage and allow appropriate surgery, which imply a low
      maternal and fetal morbidity as well as maintained fertility.

PMID- 21849135
TI  - [Improved prognosis of cystinosis achieved by treatment with cysteamine and by
      kidney transplantation].
AB  - Cystinosis is a rare, autosomal recessive disease with cystine deposits in
      different tissues. First signs come from kidneys and eyes, but during progression
      of the disease other organs can also be affected. Previously, patients with
      cystinosis had a very poor prognosis, but it is now considerably improved due to
      new methods of treatment. The purpose of this paper is to give a brief review of
      the disease and discuss the significant improvement of the prognosis, which has
      been achieved by specific medical treatment with cystine-depleting agents, and,
      if needed, by kidney transplantation.

PMID- 21849136
TI  - [Haemolytic anaemia as a complication to intravenous infusion of human
      immunoglobulin].
AB  - A 85-year-old female treated for chronic inflammatory demyelinating
      polyradiculoneuropathy had three episodes of anaemia one week following treatment
      with large doses (2g/kg body weight) of immunoglobulin (Ig). At the final
      episode, she presented with haemolytic anaemia with fatigue, jaundice and loss of
      appetite. During the next two months anaemia was recognized in two additional
      cases. Subsequently, a series of twelve conseuntively studied IVIg treated
      patients showed a significant decrease of haemoglobin of 0.80 mmol/l 8-15 days
      after infusion. Haemolytic anaemia is a severe side effect that seems to be more
      frequent than previously recognized. It may possibly be prevented by the use of
      lyophilized Ig-preparations with low isohaemagglutinin titers or by slower Ig
      infusion rates.

PMID- 21849137
TI  - [Steatocystoma multiplex in 39 year-old female].
AB  - A clinical case of the rare disorder steatocystoma multiplex is described in a 39
      year-old female. The patient was diagnosed with generalized intradermal lesions
      that started presenting in early adulthood. There was no family history of
      similar lesions.Skin examination showed multiple, skin-coloured cystic lesions on
      the chest, abdomen, axillae and back. The patient's clinical presentations and
      history were compatible with steatocystoma multiplex. Various treatment options
      for steatocystoma multiplex and steatocystoma multiplex suppurativum have been
      published and include oral antibiotics, isotretinoin, excision and incision
      techniques.

PMID- 21849138
TI  - [Hip dislocation involving superior dislocation].
AB  - A hip dislocation is an orthopaedic emergency and requires prompt reposition.
      This case report describes a rare type of hip dislocation involving a superior
      dislocation with a fracture of caput femoris.

PMID- 21849139
TI  - [Picture of the month: insulin-related lipoatrophy].

PMID- 21849140
TI  - [Introduce the idea of comparative effectiveness research to clinical research of
      Chinese medicine].
AB  - Comparative effectiveness research (CER) has gained more and more popularity,
      which brought great response in the USA and other developed Western countries.
      There is no doubt that CER is a new idea and a milestone in health care research.
      CER is also known as "patient-centered outcomes research", which means patient is
      the core element in the whole system of CER. Chinese medicine could make new
      achievements and further development by introducing CER into clinical research.
      This article mainly introduced the background, features and contents of CER and
      summarized how to conduct CER in Chinese medicine by referring to some published
      literature in order to enlighten Chinese medicine researchers.

PMID- 21849141
TI  - [Application of differential proteomics in mechanism research of acupuncture].
AB  - Proteomics, a new branch of science, has been used to study protein expressions
      on the molecular level with a dynamic perspective. Organisms under varying states
      may express different proteins, which results in the set-up of differential
      proteomics. Research methods of differential proteomics include the separation
      and identification of proteins. Differential proteomics has a rapid development
      in recent years. In the study of acupuncture, researchers have reached certain
      achievements using differential proteomics to investigate the mechanisms of
      acupuncture treatment for some diseases, including acute spinal cord injury,
      ischemic cerebrovascular disease, Parkinson's disease and neuralgia.

PMID- 21849142
TI  - An update on Murraya koenigii spreng: a multifunctional Ayurvedic herb.
AB  - Murraya koenigii Spreng (Rutaceae), a medicinally important herb of Indian
      origin, has been used for centuries in the Ayurvedic system of medicine. Leaves,
      fruits, roots and bark of this plant are a rich source of carbazole alkaloids.
      These alkaloids have been reported for their various pharmacological activities
      such as antitumor, antiviral, anti-inflammatory, antidiarrhoeal, diuretic and
      antioxidant activities. Apart from these activities, the plant is reported to
      possess a wide spectrum of biological activities. Phytochemistry and pharmacology
      of this plant make a demand of an exhaustive review of its potential as a
      valuable therapeutic agent for the treatment and management of various ailments
      frequently affecting humans. The present review gives a detailed description of
      the phytochemical, pharmacological, clinical and pre-clinical works carried out
      on this medicinal herb and also throws light on its therapeutic potential.

PMID- 21849143
TI  - The control principle in scientific research.
AB  - The control principle is one of the four basic principles of research design.
      Without a control group, the conclusion of research will be unconvincing;
      furthermore, if the control group is not set properly, the conclusion will be
      unreliable. Generally, there is more than one control group in a multi-factor
      design. Problems like incomplete control and excessive control should be avoided.
      This article introduces the meaning and function of the control principle, common
      forms of control, common errors that researchers tend to make as well as analysis
      and differentiation of these errors.

PMID- 21849144
TI  - [A mathematical model for re-analysis of the relationship between essence of
      syndromes in traditional Chinese medicine and clinical biochemical indicators
      based on the residual-split method and its application].
AB  - Studying the essence of syndromes (Zheng) in traditional Chinese medicine (TCM)
      is a fundamental challenge in basic theoretical research of TCM. The relationship
      between any given syndrome and biochemical indicators is one of the important
      aspects of the study. As the indexes selected in each study are specific to a
      particular Western medical disease diagnosis, and the disease factor is
      inevitably introduced into the study, the effect of disease factor on the index
      changes cannot be assessed effectively by traditional data processing methods.
      This is known as "the same syndrome with different reasons", which has resulted
      in confusion in TCM research. This study aimed at providing a mathematical tool
      to address this issue. Based on information theory and the residual-split method,
      the syndrome information, which was covered in the index variation, was
      quantitatively calculated in this paper as an independent part of the disease
      factor. A mathematical model capable of objectively assessing and statistically
      testing the effect of the syndrome factor on the index changes was established.
      Applying this model to literature data of studies on the relationship between
      cyclic nucleotides and yang-deficiency syndrome showed following results. First,
      the values of yang-deficiency syndrome information were negative for cyclic
      adenosine monophosphate (cAMP) while positive for cyclic guanosine monophosphate
      (cGMP) in all included literature. This indicated that the group of yang
      deficiency syndrome was correlated with an obvious trend of reduced cAMP levels
      and increased cGMP levels. Second, the statistical test results of yang
      deficiency syndrome information of the two indexes were different among the
      literature included. The quality of original data was considered as a possible
      reason. Third, the significant differences between the yang-deficiency group of a
      specific disease and the normal group may, in some cases, be caused by a disease
      factor rather than a syndrome factor. The mathematical model provided a
      reasonable mathematical tool for the analysis of disease factor and syndrome
      factor in clinical research of TCM, suggesting that the mathematical model may
      give rise to innovative ideas and methods in the study of syndromes.

PMID- 21849145
TI  - Usage of alternative medical systems, acupuncture, homeopathy and anthroposophic
      medicine, by older German adults.
AB  - OBJECTIVE: The manifold studies on the usage of complementary and alternative
      medicine (CAM) indicate that its utilization differs with respect to socio
      cultural background, gender, age and underlying disease. This study intended to
      analyze the usage of specific CAM practices among a population of older German
      adults with health insurance coverage. METHODS: Data of 5 830 older individuals
      who participated in an anonymous cross sectional survey among German insurance
      beneficiaries were analyzed with respect to usage of CAM treatments applied by
      medical doctors or non-medical practitioners within the last 5 years. RESULTS:
      The most frequently used approaches were acupuncture/traditional Chinese medicine
      (21%), homeopathy (21%), movement therapies/physical exercises (19%),
      osteopathy/chiropractic (12%), herbs/phytotherapy (7%), diets/specific food
      recommendations (6%) and foot reflexology (5%). Anthroposophic medicine was used
      only to a minor degree. Acupuncture and homeopathy users were likely to choose
      more than one CAM treatment simultaneously, particularly the combination of
      homeopathy and acupuncture. Moreover, this study can confirm significant
      differences between women and men in the use of the main relevant CAM
      interventions. CONCLUSION: The relative proportion of acupuncture usage was
      similar to homeopathy, which is an alternative whole medical system originating
      from Western Europe. This means that an Eastern alternative system is established
      also in Germany. In several cases not only one CAM treatment was used but
      distinct combinations existed (particularly homeopathy and acupuncture); thus one
      should be cautious to draw predictive conclusions from studies with broad and
      unspecific CAM categories, for among them there are several therapies which
      should not be regarded as CAM.

PMID- 21849146
TI  - [Development of a patient-reported outcome scale for stable chronic obstructive
      pulmonary disease and its clinical applicability].
AB  - OBJECTIVE: To develop a patient-reported outcome (PRO) scale for patients with
      stable chronic obstructive pulmonary disease (sCOPD) and to study its clinical
      applicability in traditional Chinese medicine (TCM). METHODS: According to
      standardized procedures, the test version of PRO scale for sCOPD (sCOPD-PRO
      scale) was developed based on the theory of "unity of body and spirit" and was
      used to test 324 patients selected from six clinical centers. Five methods were
      used to analyze the items; the reliability, validity and responsiveness of the
      remaining items of the scale were evaluated. RESULTS: (1) sCOPD-PRO consisted of
      23 items after item analysis, and according to the content of each item, these
      items could be grouped into four domains, namely, lung and kidney deficiency
      symptom, spleen deficiency symptom, functional activities and emotional impact.
      (2) Cronbach's alpha coefficient for sCOPD-PRO scale was more than 0.75 in four
      domains and total scores. (3) sCOPD-PRO scale and St. George's Respiratory
      Questionnaire (SGRQ) were moderately correlated or highly correlated in
      corresponding domains: the correlation coefficient between the total score of
      sCOPD-PRO scale and the total score of SGRQ was 0.72 (P<0.01), the correlation
      coefficient between functional activities domain of sCOPD-PRO scale and activity
      domain of SGRQ was 0.77 (P<0.01), and the correlation coefficient between
      emotional impact domain of sCOPD-PRO scale and impact domain of SGRQ was 0.51
      (P<0.01). Factor analysis revealed that four factors could explain 65.06% of the
      total variance. (4) The four domains and total scores of sCOPD-PRO scale were
      significantly different before and after intervention in TCM group and Western
      medicine group (P<0.01); moreover, the effect size and standardized response mean
      of two groups were more than 0.4. CONCLUSION: The development process and method
      of sCOPD-PRO scale, which is based on the theories of "unity of body and spirit",
      are standard, and the reliability, validity and responsiveness of the scale are
      sound and can be relied upon for sCOPD clinical efficacy evaluation of TCM.

PMID- 21849147
TI  - [Efficacy of Chinese herbal medicine Mailuo Shutong Granule and Hirudoid cream
      for chronic venous disorder-induced pigmentation in lower extremities: a
      prospective, randomized controlled trial].
AB  - BACKGROUND: Chronic venous disorder (CVD) of the lower extremities generally
      induces dermatologic complications in lower extremity skin, such as
      hyperpigmentation. If not treated effectively, the lesions may develop into
      severe outcomes, including dermal ulcer or necrosis. OBJECTIVE: To evaluate the
      clinical efficacy of Mailuo Shutong Granule, a compound traditional Chinese
      herbal medicine, and Hirudoid cream (heparinoid), in treatment of patients with
      dermal hyperpigmentation of skin caused by CVD. DESIGN, SETTING, PARTICIPANTS AND
      INTERVENTIONS: A total of 108 CVD outpatients with pigmentation from Department
      of Vascular Surgery, Shanghai Changhai Hospital were randomly divided into Mailuo
      Shutong group, Hirudoid group and combined therapy group, with 36 patients in
      each group. Patients in the Mailuo Shutong group and the Hirudoid group were
      treated with Mailuo Shutong Granule or Hirudoid cream, respectively, while those
      in the combined therapy group were treated with Mailuo Shutong Granule plus
      Hirudoid cream. They were all treated for 28 d. MAIN OUTCOME MEASURES: Before and
      after the 28-day treatment, area and average gray value of pigmentation lesions
      were measured and evaluated. RESULTS: Thirty-three cases in the Mailuo Shutong
      group, 34 cases in the Hirudoid group and 31 cases in the combined therapy group
      were included for analysis. After treatment, area of pigmentation decreased and
      average gray value of pigmentation declined in all the 3 groups (P<0.05). The
      reductions of area and average gray value in the combined therapy group were more
      significant than those in the Mailuo Shutong group and Hirudoid group (P<0.05).
      There were no differences in improvement of pigmentation between the Mailuo
      Shutong group and Hirudoid group (P>0.05). CONCLUSION: These data suggest that
      both Mailuo Shutong Granule and Hirudoid cream can improve CVD-induced
      hyperpigmentation, and combined treatment of the two drugs results in better
      clinical efficacy.

PMID- 21849148
TI  - [Effects of Chinese herbal medicines for regulating liver qi on expression of 5
      hydroxytryptamine 3B receptor in hypothalamic tissues of rats with anger
      emotion].
AB  - OBJECTIVE: To explore the central mechanisms of anger emotion and the effects of
      Chinese herbal medicines for regulating liver qi on the anger emotion and the
      expression level of 5-hydroxytryptamine 3B receptor (5-HT3BR) in rat
      hypothalamus. METHODS: Rat models of anger-in or anger-out emotions were prepared
      by the methods of resident intruder paradigm. There were five groups in this
      study: control, anger-in model, Jingqianshu Granule-treated anger-in, anger-out
      model and Jingqianping Granule-treated anger-out groups. The treatment groups
      were orally given Jingqianshu granules and Jingqianping granules respectively,
      and the model groups and the normal control group were given sterile water. Open
      field test and sucrose preference test were used to evaluate behavioristics of
      the rats. Semi-quantitative reverse transcription-polymerase chain reaction and
      Western blot methods were used to detect the expression levels of 5-HT3BR mRNA
      and protein in the rat hypothalamus. RESULTS: The expression of 5-HT3BR in
      hypothalamus of anger-in model rats increased obviously (P<0.01) and that of
      anger-out model rats decreased obviously (P<0.01) compared with the normal
      control group. Compared with the model group, the expressions of 5-HT3BR in the
      treatment groups were significantly improved (P<0.01) after treatment, and
      recovered to normal level. CONCLUSION: The anger-in stimulation obviously
      increases hypothalamic 5-HT3BR expression and the anger-out emotion can obviously
      reduce its expression. Chinese herbal medicines for regulating liver qi may treat
      anger emotion in rats by improving the hypothalamic 5-HT3BR protein and gene
      expression levels.

PMID- 21849149
TI  - [Chinese herbal medicine Xiayuxue Decoction inhibits liver angiogenesis in rats
      with carbon tetrachloride-induced liver fibrosis].
AB  - OBJECTIVE: To evaluate the effects of Xiayuxue Decoction, a compound traditional
      Chinese medicine, on liver angiogenesis in rats with carbon tetrachloride
      (CCl(4))-induced liver fibrosis. METHODS: Liver cirrhosis was induced by
      intraperitoneal injection of 50% CCl(4)-olive oil solution at the dose of 1 mL/kg
      body weight, twice per week for 9 consecutive weeks. After 3- and 6-week
      injection, 6 rats in the normal group and 6 rats in the model group were randomly
      sacrificed for dynamic observation. The survival rats of model group were
      randomly divided into model group (n=15) and Xiayuxue Decoction group (n=11). Six
      normal rats were used as a normal control. Xiayuxue Decoction was administered
      orally starting from the 7th week for 3 weeks. At the end of the ninth week,
      animals were sacrificed and liver tissues were harvested to measure histological
      changes, activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 and protein
      expressions of platelet endothelial cell adhesion molecule-1 (CD31), von
      Willebrand factor (vWF), vascular endothelial growth factor (VEGF), vascular
      endothelial growth factor receptor-2 (VEGFR2), complement decay-accelerating
      factor (DAF) and alpha-smooth muscle actin (alpha-SMA) in the liver tissues.
      RESULTS: Compared with the normal group, liver injury, fatty degeneration and
      collagen deposition were evidently observed in the model group and protein
      expressions of CD31, vWF, VEGF, VEGFR2, DAF and alpha-SMA were gradually
      increased. In addition, the activities of MMP-2 and MMP-9 in liver tissues were
      enhanced in the model group (P<0.01). Compared with 9-week model group, liver
      injury, fatty degeneration and collagen deposition were markedly inhibited by
      Xiayuxue Decoction; protein expressions of CD31, vWF, VEGF, VEGFR2,alpha-SMA and
      DAF and activities of MMP-2 and MMP-9 in the liver tissues were decreased in the
      Xiayuxue Decoction group (P<0.01). CONCLUSION: The angiogenesis is evident and
      aggravating gradually during the progression of liver cirrhosis induced by
      CCl(4). Xiayuxue Decoction inhibits the angiogenesis by decreasing the activities
      of MMP-2 and MMP-9, inhibiting the activation of hepatic stellate cells, and
      damaging the new vessel integrality.

PMID- 21849150
TI  - [Active ingredients of Plastrum Testudinis inhibit epidermal stem cell apoptosis
      in serum-deprived culture].
AB  - OBJECTIVE: To investigate the effects of active ingredients of Plastrum
      Testudinis (PT) on serum deprivation-induced apoptosis of epidermal stem cells
      (ESCs). METHODS: ESCs were isolated from the back skin of fetal Sprague-Dawley
      rats with 2 weeks of gestational age and were divided into normal group (10%
      fetal bovine serum), control group (serum-deprived culture) and groups treated
      with serum deprivation plus active ingredients of PT, including ethyl acetate
      extract (2B), stearic acid ethyl ester (S6), tetradecanoic acid sterol ester (S8)
      and (+)-4-cholesten-3-one (S9). The vitality of ESCs after 24, 48 and 72 h of
      culture was measured with MTT method; apoptotic ESCs double-stained with Annexin
      V-FITC and propidium iodine were detected by flow cytometry (FCM); Bcl-2 and
      caspase-3 expressions were measured by Western blotting. RESULTS: MTT results
      indicated that the vitality of ESCs in the active ingredients of PT groups at 48
      h was increased compared with the control group and 2B had better effects than
      the others. FCM results indicated that 2B had the most significant anti-apoptotic
      effect compared with the control as well as S6, S8 and S9. Western blot results
      indicated that 2B, S6, S8 and S9 up-regulated the expression of Bcl-2 protein and
      down-regulated the expression of caspase-3 protein compared with the control.
      CONCLUSION: Ethyl acetate extract of Plastrum Testudinis inhibits epidermal stem
      cell apoptosis in serum-deprived culture by regulating the expressions of Bcl-2
      and caspase-3 proteins and has a stronger anti-apoptotic effect than its
      constituents S6, S8 and S9.

PMID- 21849151
TI  - [Effects of ethanol extract of Rhizome Pinelliae Preparata on intracellular pH
      value of human gastric adenocarcinoma cells].
AB  - OBJECTIVE: To observe the effects of ethanol extract of Rhizome Pinelliae
      Preparata on the intracellular pH value of human gastric cancer SGC7901 cells.
      METHODS: After coculturing SGC7901 cells with ethanol extract of Rhizome
      Pinelliae Preparata (1, 0.5, 0.25 and 0.125 mg/mL), cell viability was evaluated
      by chromatometry with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) staining. Intracellular pH value of SGC7901 cells was measured in
      the monolayer by using the pH-sensitive fluorescent probe 2,7-bis-(2
      carboxyethyl)-5-carboxyfluorescein-acetoxymethyl ester. The extracellular pH
      value of culture medium was measured by a pH211 Calibration Check Microprocessor
      pH Meter. Half-inhibitory concentration (IC(50)) of ethanol extract culture to
      SGC7901 cells was decided by the MTT method and expressions of vacuolar-H(+)
      ATPase (V-ATPase) and Na(+)/H(+) exchanger isoform 1 (NHE1) mRNAs were examined
      by the method of fluorescence quantitative-polymerase chain reaction after 72 h
      of drug treatment. RESULTS: Ethanol extract of Rhizome Pinelliae Preparata at
      different concentrations significantly inhibited the proliferation of SGC7901
      cells, lowered the intracellular pH values and heightened the extracellular pH
      values. The IC(50) of 72 h culture was 0.5mg/mL and it inhibited the expressions
      of V-ATPase and NHE1 mRNAs. CONCLUSION: Ethanol extract of Rhizome Pinelliae
      Preparata can lower down the intracellular pH value of SGC7901 cells. The
      mechanism may be related to inhibiting the expressions of V-ATPase and NHE1
      mRNAs.

PMID- 21849152
TI  - Analysis of the capability of ultra-highly diluted glucose to increase glucose
      uptake in arsenite-stressed bacteria Escherichia coli.
AB  - OBJECTIVE: Whether ultra-highly diluted homeopathic remedies can affect living
      systems is questionable. Therefore, this study sees value in the analysis of
      whether homeopathically diluted glucose 30C has any effect on Escherichia coli
      exposed to arsenite stress. METHODS: E. coli were cultured to their log phase in
      standard Luria-Bertani medium and then treated with either 1 mmol/L or 2 mmol/L
      sodium arsenite, with or without supplementation of either 1% or 3% glucose, an
      ultra-highly diluted and agitated ethanolic solution (70%) of glucose (diluted
      10(60) times), glucose 30C or 70% ethanol (placebo) in the medium. Glucose
      uptake, specific activities of hexokinase and glucokinase, membrane potential,
      intracellular adenosine triphosphate (ATP) and expression of glucose permease in
      E. coli were analyzed at two different time intervals. Arsenic content in E. coli
      (intracellular) and in the spent medium (extracellular) was also determined.
      RESULTS: In arsenite-exposed E. coli, the glucose uptake increased along with
      decreases in the specific activities of hexokinase and glucokinase, intracellular
      ATP and membrane potential and an increase in the gene expression level of
      glucose permease. Glucose uptake increased further by addition of 1%, 3% or ultra
      highly diluted glucose in the medium, but not by the placebo. CONCLUSION: The
      results demonstrated the efficacy of the ultra-highly diluted and agitated
      glucose in mimicking the action of actual glucose supplementation and its ability
      to modulate expressions of hexokinase and glucokinase enzymes and glucose
      permease genes, thereby validating the efficacy of ultra-high dilutions used in
      homeopathy.

PMID- 21849153
TI  - Effects of Murraya koenigii leaf extract on impaired gastrointestinal motility in
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: The present study was to investigate the effects of Murraya koenigii
      leaf (MKL), an Indian herb, on glucose homeostasis, intestinal transit time,
      response to exogenous acetylcholine of smooth muscles of distal colon, and
      intestinal thiobarbituric acid reactive substance (TBARS) level in streptozotocin
      (STZ)-induced diabetic rats. METHODS: Male adult Wistar rats were used in this
      study. Diabetes was induced in the rats by STZ (70 mg/kg, intravenously). The
      treatments of MKL extract (300 and 500 mg/kg) and glibenclamide were started
      after stabilization of blood glucose level (13 d after single dose of STZ), while
      the standard drug cisapride or vitamin E was given from the last week (8th week)
      of experimentation. At the end of the study, the rats were sacrificed and
      evaluated for gastrointestinal motility, the contractile response of distal
      colons and the TBARS content. The gastrointestinal motility was evaluated by
      measuring the intestinal transit rate of charcoal meal. The contractile response
      of distal colon was measured in terms of evaluating the dose-response curve with
      increasing doses of acetylcholine, and the TBARS content was measured by
      calculating the level of polyunsaturated fatty acid in homogenates of intestines
      of the diabetic rats. RESULTS: MKL significantly decreased the blood glucose
      level at the 30th (P<0.05) and 60th (P<0.01) day of MKL administration (300 and
      500 mg/kg). The gastrointestinal motility significantly (P<0.05) reduced after 9
      weeks in diabetic rats and it was correlated to the decrease of the percent
      response of acetylcholine on distal colons (P<0.01) and the increase of TBARS (as
      an index of oxidative stress) in intestines (P<0.05), while prior treatment with
      MKL (300 and 500 mg/kg) up to 9 weeks increased the gastrointestinal motility
      demonstrated by the increase in the activation of cholinergic response to
      acetylcholine on distal colons (P<0.05). The TBARS also decreased after 9-week
      treatment with MKL (P<0.05). CONCLUSION: The present study suggested that MKL had
      protective effect against gastrointestinal disturbances in diabetes by
      controlling glucose level as well as defending against peripheral damage of
      cholinergic neurons by providing antioxidant shelter, so it may be helpful in
      diabetic patients with impaired gastrointestinal motility.

PMID- 21849154
TI  - Experience on clinical application of Chinese herbal medicine Yi Guan Jian
      decoction.
AB  - Yi Guan Jian decoction is a traditional Chinese medicine formula noted in Wei Yu
      huang's Xu Ming Yi Lei An (Supplement to the Classified Medical Records of Famous
      Physicians). Acne vulgaris and chronic pelvic inflammation could be successfully
      treated by the decoction following the principle of formula corresponding to
      syndromes. The identical characteristics of constitution are found among the
      patients treated by the decoction, known as the "Yi Guan Jian constitution". It
      indicates that patients can be treated according to the constitutional
      characteristics.

PMID- 21849155
TI  - Comparative study on WHO Western Pacific region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      syndrome differentiation of combined visceral diseases.
AB  - Yi Guan Jian decoction is a traditional Chinese medicine formula noted in Wei Yu
      huang's Xu Ming Yi Lei An (Supplement to the Classified Medical Records of Famous
      Physicians). Acne vulgaris and chronic pelvic inflammation could be successfully
      treated by the decoction following the principle of formula corresponding to
      syndromes. The identical characteristics of constitution are found among the
      patients treated by the decoction, known as the "Yi Guan Jian constitution". It
      indicates that patients can be treated according to the constitutional
      characteristics.

PMID- 21849156
TI  - Myeloid differentiation protein 2 silencing decreases LPS-induced cytokine
      production and TLR4/MyD88 pathway activity in alveolar macrophages.
AB  - Lipopolysaccharides (LPSs) activate the innate immune response during Gram
      negative bacterial infections through the Toll-like receptor 4 (TLR4)/myeloid
      differentiation protein 2 (MD-2) complex. MD-2 binds LPS with high affinity and
      is critical for TLR4-dependent signal transduction. However, the exact role of MD
      2 on LPS signal transduction and cytokine production in alveolar macrophages
      (AMs) remains unclear. This study showed that the transcription levels of MD-2,
      TLR4 and MyD88 in the NR8383 cell line were up-regulated after LPS stimulation
      and that the increased transcript levels were attenuated after RNA interference
      of MD-2. Similarly, LPS induced increases in TNF-alpha, IL-1beta and IL-6 protein
      levels in NR8383 cell supernatants was significantly inhibited by MD-2 silencing.
      These results suggest that in association with the TLR4/MyD88 signaling pathway
      LPS-induced cytokine production can be partially reduced by MD-2 silencing in the
      rat pulmonary alveolar macrophage cell line NR8383. MD-2 silencing was proved to
      be a useful tool for testing the role of MD-2 in the LPS signaling pathway and
      may be a potential therapeutic tool against LPS-induced lung inflammation.

PMID- 21849157
TI  - Antibacterial and anti-biofilm effects of cathelicidin peptides against pathogens
      isolated from cystic fibrosis patients.
AB  - Six different cathelicidin-derived peptides were compared to tobramycin for
      antibacterial and anti-biofilm effects against S. aureus, P. aeruginosa, and S.
      maltophilia strains isolated from cystic fibrosis patients. Overall, SMAP-29,
      BMAP-28, and BMAP-27 showed relevant antibacterial activity (MIC(50) 4-8MUg/ml),
      and in some cases higher than tobramycin. In contrast, indolicidin, LL-37, and
      Bac7(1-35) showed no significant antimicrobial activity (MIC(50)>32MUg/ml).
      Killing kinetics experiments showed that in contrast to tobramycin the active
      cathelicidin peptides exert a rapid bactericidal activity regardless of the
      species tested. All three peptides significantly reduced biofilm formation by S.
      maltophilia and P. aeruginosa strains at 1/2* MIC, although at a lower extent
      than tobramycin. In addition, BMAP-28, as well as tobramycin, was also active
      against S. aureus biofilm formation. Preformed biofilms were significantly
      affected by bactericidal SMAP-29, BMAP-27 and BMAP-28 concentrations, although at
      a lesser extent than tobramycin. Overall, our results indicate the potential of
      some cathelicidin-derived peptides for the development of novel therapeutic
      agents for cystic fibrosis lung disease.

PMID- 21849158
TI  - Parasiticidal activity of Haemaphysalis longicornis longicin P4 peptide against
      Toxoplasma gondii.
AB  - The Haemaphysalis longicornis longicin P4 peptide is an active part peptide
      produced by longicin which displays bactericidal activity against both Gram
      negative and Gram-positive bacteria and other microorganisms. In the present
      study, the effect of the longicin P4 peptide on the infectivity of Toxoplasma
      gondii parasites was examined in vitro. Tachyzoites of T. gondii incubated with
      longicin P4 had induced aggregation and lost the trypan blue dye exclusion
      activity and the invasion ability into the mouse embryonal cell line (NIH/3T3).
      Longicin P4 bound to T. gondii tachyzoites, as demonstrated by fluoresce
      microscopic analysis. An electron microscopic analysis and a fluorescence
      propidium iodide exclusion assay of tachyzoites exposed to longicin P4 revealed
      pore formation in the cellular membrane, membrane disorganization, and hollowing
      as well as cytoplasmic vacuolization. The number of tachyzoites proliferated in
      mouse macrophage cell line (J774A.1) was significantly decreased by incubation
      with longicin P4. These findings suggested that longicin P4 conceivably impaired
      parasite membranes, leading to the destruction of Toxoplasma parasites in J774A.1
      cells. Thus, longicin P4 is an interesting candidate for antitoxoplasmosis drug
      design that causes severe toxicity to T. gondii and plays an important role in
      reducing cellular infection. This is the first report showing that longicin P4
      causes aggregation and membrane injury of parasites, leading to Toxoplasma
      tachyzoite destruction.

PMID- 21849159
TI  - The MYCN oncogene and differentiation in neuroblastoma.
AB  - Childhood neuroblastoma exhibits a heterogeneous clinical behavior ranging from
      low-risk tumors with the ability to spontaneously differentiate and regress, to
      high-risk tumors causing the highest number of cancer related deaths in infants.
      Amplification of the MYCN oncogene is one of the few prediction markers for
      adverse outcome. This gene encodes the MYCN transcriptional regulator
      predominantly expressed in the developing peripheral neural crest. MYCN is vital
      for proliferation, migration and stem cell homeostasis while decreased levels are
      associated with terminal neuronal differentiation. Interestingly, high-risk
      tumors without MYCN amplification frequently display increased c-MYC expression
      and/or activation of MYC signaling pathways. On the other hand, downregulation of
      MYCN leads to decreased proliferation and differentiation, emphasizing the
      importance of MYC signaling in neuroblastoma biology. Furthermore, expression of
      the neurotrophin receptor TrkA is associated with good prognosis, the ability to
      differentiate and spontaneous regression while expression of the related TrkB
      receptor is correlated with bad prognosis and MYCN amplification. Here we discuss
      the role of MYCN in neuroblastoma with a special focus on the contribution of
      elevated MYCN signaling for an aggressive and undifferentiated phenotype as well
      as the potential of using MYCN as a therapeutic target.

PMID- 21849160
TI  - Grand challenges in neurology: a global call for action.

PMID- 21849162
TI  - Controlling machines with just the power of thought.

PMID- 21849163
TI  - Kristine Yaffe: delving into the varied depths of dementia.

PMID- 21849165
TI  - Cerebral palsy: clinical care and neurological rehabilitation.
AB  - Cerebral palsy (CP) is defined as motor impairment that limits activity, and is
      attributed to non-progressive disturbances during brain development in fetuses or
      infants. The motor disorders of CP are frequently accompanied by impaired
      cognition, communication, and sensory perception, behavioural abnormalities,
      seizure disorders, or a combination of these features. CP is thought to affect
      three to four individuals per 1000 of the general population. The incidence,
      prevalence, and most common causes of CP have varied over time because of changes
      in prenatal and paediatric care. Medical management of children and adults
      involves care from primary-care physicians with input from specialists in
      neurology, orthopaedics, and rehabilitation medicine. Physicians should also work
      in conjunction with rehabilitation therapists, educators, nurses, social care
      providers, and schoolteachers. The focus of rehabilitation treatment has recently
      shifted to neurological rehabilitation in response to increasing evidence for
      neuroplasticity. This approach aims to improve development and function by
      capitalising on the innate capacity of the brain to change and adapt throughout
      the patient's life. As the life expectancy of individuals with CP approaches that
      of the general population, therapies must be developed that address the needs of
      adults ageing with disability.

PMID- 21849166
TI  - Neuroschistosomiasis: clinical symptoms and pathogenesis.
AB  - Neuroschistosomiasis, referring to schistosomal involvement of the CNS, when
      symptomatic, is a severe disorder in which prognosis depends largely on early
      diagnosis and treatment. It is an underdiagnosed disorder, but has been
      increasingly reported in populations in endemic areas and in tourists. CNS
      involvement can occur at any time during schistosomal infection. Both the brain
      and the spinal cord can be affected. Schistosoma mansoni and Schistosoma
      haematobium usually cause myelopathy, whereas Schistosoma japonicum usually
      causes encephalic disease. There are substantial differences in the pathogenesis,
      clinical presentation, and outcome of the neurological disorder, depending on the
      phase and clinical form of schistosomiasis in which it occurs.

PMID- 21849167
TI  - A training program to improve gait while dual tasking in patients with
      Parkinson's disease: a pilot study.
AB  - Impairments in the ability to perform another task while walking (ie, dual
      tasking [DT]) are associated with an increased risk of falling. Here we describe
      a program we developed specifically to improve DT performance while walking based
      on motor learning principles and task-specific training. We examined feasibility,
      potential efficacy, retention, and transfer to the performance of untrained tasks
      in a pilot study among 7 patients with Parkinson's disease (PD). Seven patients
      (Hoehn and Yahr stage, 2.1+/-0.2) were evaluated before, after, and 1 month after
      4 weeks of DT training. Gait speed and gait variability were measured during
      usual walking and during 4 DT conditions. The 4-week program of one-on-one
      training included walking while performing several distinct cognitive tasks. Gait
      speed and gait variability during DT significantly improved. Improvements were
      also seen in the DT conditions that were not specifically trained and were
      retained 1 month after training. These initial findings support the feasibility
      of applying a task-specific DT gait training program for patients with PD and
      suggest that it positively affects DT gait, even in untrained tasks. The present
      results are also consistent with the possibility that DT gait training enhances
      divided attention abilities during walking.

PMID- 21849168
TI  - Effect of gravity on robot-assisted motor training after chronic stroke: a
      randomized trial.
AB  - OBJECTIVES: To determine the efficacy of 2 distinct 6-week robot-assisted
      reaching programs compared with an intensive conventional arm exercise program
      (ICAE) for chronic, stroke-related upper-extremity (UE) impairment. To examine
      whether the addition of robot-assisted training out of the horizontal plane leads
      to improved outcomes. DESIGN: Randomized controlled trial, single-blinded, with
      12-week follow-up. SETTING: Research setting in a large medical center.
      PARTICIPANTS: Adults (N=62) with chronic, stroke-related arm weakness stratified
      by impairment severity using baseline UE motor assessments. INTERVENTIONS: Sixty
      minutes, 3 times a week for 6 weeks of robot-assisted planar reaching (gravity
      compensated), combined planar with vertical robot-assisted reaching, or intensive
      conventional arm exercise program. MAIN OUTCOME MEASURE: UE Fugl-Meyer Assessment
      (FMA) mean change from baseline to final training. RESULTS: All groups showed
      modest gains in the FMA from baseline to final with no significant between group
      differences. Most change occurred in the planar robot group (mean change +/- SD,
      2.94 +/- 0.77; 95% confidence interval [CI], 1.40-4.47). Participants with
      greater motor impairment (n=41) demonstrated a larger difference in response
      (mean change +/- SD, 2.29 +/- 0.72; 95% CI, 0.85-3.72) for planar robot-assisted
      exercise compared with the intensive conventional arm exercise program (mean
      change +/- SD, 0.43 +/- 0.72; 95% CI, -1.00 to 1.86). CONCLUSIONS: Chronic UE
      deficits because of stroke are responsive to intensive motor task training.
      However, training outside the horizontal plane in a gravity present environment
      using a combination of vertical with planar robots was not superior to training
      with the planar robot alone.

PMID- 21849169
TI  - Transient facial subcutaneous emphysema: an unusual complication of liquid
      nitrogen spray cryoablation of Barrett's esophagus.

PMID- 21849170
TI  - Disease burden due to pre-eclampsia/eclampsia and the Ethiopian health system's
      response.
AB  - OBJECTIVE: To assess the maternal disease burden due to pre-eclampsia/eclampsia
      in Ethiopia and the national health system's readiness to respond to the needs of
      women with pre-eclampsia/eclampsia. METHODS: The national emergency obstetric and
      newborn care (EmONC) assessment entailed collecting information from 112
      hospitals and 685 health centers in Ethiopia, focusing on their infrastructure,
      the services they provided, human resources, equipment and supplies, case load,
      and mortality due to pre-eclampsia/eclampsia. RESULTS: Pre-eclampsia/eclampsia
      complicated 1.2% of all institutional deliveries. Given the low institutional
      delivery rate and an expected incidence of 2%-8% of all deliveries, this implies
      that only a small fraction (3.8%) of all women with pre-eclampsia/eclampsia
      received care at health facilities. 11% of all maternal deaths and 16% of direct
      maternal deaths were due to this obstetric complication. The cause-specific case
      fatality rate was high (3.6%). Availability of urine test strips,
      anticonvulsants, antihypertensives, and actual service provision to treat these
      diseases was limited, especially at health centers. CONCLUSION: The salutary
      effects of the national EmONC assessment were immediate, as evidenced by how
      quickly the release of the Ethiopian report led to important national efforts to
      improve maternal and newborn health. Expansion of health services should be
      augmented with periodic assessments of logistics and quality-related issues to
      assure functioning facilities for women accessing obstetric services.

PMID- 21849172
TI  - Diagnostic yield of muscle fibre conduction velocity in myopathies.
AB  - We prospectively assessed diagnostic yield of muscle fiber conduction velocity
      (MFCV) studies in patients with signs and symptoms suggestive of a myopathy.
      Results were analysed with respect to the final diagnosis, and compared to the
      reference standard, which was qualitative electromyography (EMG), turns-amplitude
      analysis (TAA), and muscle biopsy. We included 125 patients, in whom a myopathy
      was diagnosed in 71, and a neuromuscular disorder was excluded in 54. Sensitivity
      of MFCV for the presence of a myopathy was 84%, and specificity 83%. Diagnostic
      yield of MFCV was superior to EMG, TAA, and muscle biopsy in patients with
      metabolic myopathies, non-dystrophic myopathies, and channelopathies. We
      concluded that measurement of MFCV is a quantitative EMG technique with a high
      diagnostic yield. In certain myopathies, MFCV may be more informative than
      conventional EMG examination.

PMID- 21849171
TI  - The King-Devick test and sports-related concussion: study of a rapid visual
      screening tool in a collegiate cohort.
AB  - OBJECTIVE: Concussion, defined as an impulse blow to the head or body resulting
      in transient neurologic signs or symptoms, has received increasing attention in
      sports at all levels. The King-Devick (K-D) test is based on the time to perform
      rapid number naming and captures eye movements and other correlates of suboptimal
      brain function. In a study of boxers and mixed martial arts (MMA) fighters, the K
      D test was shown to have high degrees of test-retest and inter-rater reliability
      and to be an accurate method for rapidly identifying boxers and mixed martial
      arts fighters with concussion. We performed a study of the K-D test as a rapid
      sideline screening tool in collegiate athletes to determine the effect of
      concussion on K-D scores compared to a pre-season baseline. METHODS: In this
      longitudinal study, athletes from the University of Pennsylvania varsity
      football, sprint football, and women's and men's soccer and basketball teams
      underwent baseline K-D testing prior to the start of the 2010-11 playing season.
      Post-season testing was also performed. For athletes who had concussions during
      the season, K-D testing was administered immediately on the sidelines and changes
      in score from baseline were determined. RESULTS: Among 219 athletes tested at
      baseline, post-season K-D scores were lower (better) than the best pre-season
      scores (35.1 vs. 37.9s, P=0.03, Wilcoxon signed-rank test), reflecting mild
      learning effects in the absence of concussion. For the 10 athletes who had
      concussions, K-D testing on the sidelines showed significant worsening from
      baseline (46.9 vs. 37.0s, P=0.009), with all except one athlete demonstrating
      worsening from baseline (median 5.9s). CONCLUSION: This study of collegiate
      athletes provides initial evidence in support of the K-D test as a strong
      candidate rapid sideline visual screening tool for concussion. Data show
      worsening of scores following concussion, and ongoing follow-up in this study
      with additional concussion events and different athlete populations will further
      examine the effectiveness of the K-D test.

PMID- 21849173
TI  - Serial nerve conduction studies provide insight into the pathophysiology of
      Guillain-Barre and Fisher syndromes.
AB  - The electrodiagnosis of Guillain-Barre syndrome (GBS) can be broadly divided into
      acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal
      neuropathy (AMAN). Fisher syndrome (FS) is a variant of GBS, although the
      underlying neuropathy of FS has yet to be established. Serial nerve conduction
      studies (NCS) can provide further insight into the likely pathophysiology by
      further subtyping of GBS and FS. We present a patient with an initial diagnosis
      of AIDP in whom repeated NCS revealed the AMAN variant. This led us to
      investigate serial NCS in five patients with GBS, FS and FS/GBS overlap
      presenting over a period of a year. Three patients with AIDP showed a gradual
      increase in distal motor latencies during the acute phase of illness. NCS of two
      patients with FS and FS/GBS overlap showed no demyelinating features suggesting
      underlying axonal neuropathy in this group of patients. The importance of serial
      NCS in establishing the underlying pattern of neuropathy in GBS and FS is further
      emphasized in this study. Larger studies incorporating serial NCS are required to
      confirm the observations seen in our case series especially when pathological
      studies are often not justified in this group of patients.

PMID- 21849174
TI  - Aspects of speech rate and regularity in Parkinson's disease.
AB  - The hypokinetic dysarthria of Parkinson's disease (PD) has been defined as a
      multidimensional impairment leading to abnormalities in speech breathing,
      phonation, articulation and prosody. The aspect of prosody can be subdivided into
      further dimensions, as for example stress and accentuation, intonation
      variability and speech rate and regularity. According to available data from
      literature and findings of our own published studies, the present review
      illuminates the concept that inconstancies of speech fluency in PD are
      characterized by modifications of the arrangement of speech pauses and by a
      tendency of pace acceleration in the course of the performance. Furthermore, on
      the level of single utterances, Parkinsonian speakers feature significant
      difficulties to steadily repeat single syllables without accelerating or slowing
      down the pace as we were able to show in a series of published investigations.
      Evidence from literature and our own work justifies the hypothesis that the
      characteristic abnormalities in speech articulatory rate and regularity might
      serve as a marker of disease progression in PD.

PMID- 21849175
TI  - Cardiovascular autonomic dysfunction in MSA and Parkinson's disease: similarities
      and differences.
AB  - In Parkinsons disease and multiple system atrophy (MSA), cardiovascular
      dysfunction may occur for a variety of reasons and may manifest itself through
      inappropriate changes and/or levels in blood pressure, heart rate and/or regional
      vascular perfusion in a range of situations. The early occurrence of orthostatic
      hypotension often leads to consideration of MSA, especially in the presence of
      other features of autonomic failure. Orthostatic hypotension, however, is
      increasingly recognised in PD, and especially with increasing age, severity of
      disease and as a result of drug therapy, sometimes for associated disorders.
      Investigation of cardiovascular autonomic dysfunction in Parkinsonism is
      therefore important for a variety of reasons, that include determining the
      precise diagnosis and in predicting prognosis. In Parkinsonian disorders,
      understanding the pathophysiological basis of the cardiovascular autonomic
      dysfunction aids targeting of therapy, improves management strategies and
      provides benefit for such patients.

PMID- 21849176
TI  - Is there a need to redefine Parkinson's disease?
AB  - Parkinson's disease (PD) has initially been described as a clinical syndrome,
      although the exact definition has changed over the past centuries. The inclusion
      of the pathological changes added another level of complexity, with Lewy bodies,
      synuclein deposits and neuronal loss in the substantia nigra being used
      alternatively. A third level of complexity was added with the recognition of
      genetic mutations resulting in parkinsonism, sometimes with and sometimes without
      Lewy body deposition, and the identification of frequent additional important pre
      motor manifestations. These different points of view on the definition of PD have
      important implications on the study of the etiology and even the therapy of PD.

PMID- 21849177
TI  - Inter-dependence of vitamin D levels with serum lipid profiles in multiple
      sclerosis.
AB  - OBJECTIVE: To assess whether vitamin D (VD) levels in multiple sclerosis (MS)
      patients exhibit inter-dependence with serum lipid profile variables (serum
      cholesterol, high-density lipoprotein or HDL, low-density lipoprotein or LDL, and
      triglycerides) and to investigate the associations with clinical disability
      measures. METHODS: The study population consisted of consecutive 178 MS patients
      (age: 46.6+/-10.6 years; disease duration: 13.8+/-10.3 years). The patients were
      assessed for fasting lipid profile and VD obtained concomitantly. Neurological
      disability using the Expanded Disability Status Scale (EDSS) was obtained within
      +/-6 months of the lipid profile. The associations between the HDL, LDL, total
      cholesterol and total cholesterol to HDL ratio with deseasonalized VD levels and
      their relationships with EDSS and the MS Severity Score (MSSS) were analyzed
      using regression methods. RESULTS: The cholesterol to HDL ratio was associated
      with the deseasonalized VD (r(p)=-0.18, p=0.019) and VD3 (r(p)=-0.17, p=0.028)
      levels. The probability of VD3 sufficiency was associated with HDL>60 mg/dl
      status (p=0.015, OR=0.42, 95% CI=0.20 to 0.86) and with total cholesterol to HDL
      ratio<3.5 status (p<0.001, OR=4.07, 95% CI=2.03 to 8.15). In stepwise regression
      models, EDSS was associated with total cholesterol to HDL ratio (p=0.008,
      r(p)=0.21) whereas MSSS was associated with deseasonalized 25-hydroxy VD3
      (p=0.021, r(p)=-0.18). The probability of EDSS>=4.0 was also associated with
      total cholesterol to HDL ratio (p=0.011, OR=1.59, 95% CI=1.11 to 1.26).
      CONCLUSIONS: The results suggest inter-dependence between the total cholesterol
      to HDL ratio and deseasonalized vitamin D levels in MS patients. Disability
      measures in MS are also associated with these inter-dependent variables.

PMID- 21849178
TI  - The role of magnetic resonance imaging in the detection of prostate cancer.

PMID- 21849179
TI  - Changes in training and education.

PMID- 21849180
TI  - Nephron sparing surgery for Wilms tumor--where is the future?

PMID- 21849181
TI  - Presacral and retroperitoneal lymph node involvement in urothelial bladder
      cancer: results of a prospective mapping study.
AB  - PURPOSE: We evaluated the incidence of positive lymph nodes in the presacral and
      retroperitoneal regions in patients who underwent radical cystectomy and extended
      pelvic lymph node dissection for urothelial bladder cancer. MATERIALS AND
      METHODS: As part of a prospective mapping study, 143 patients underwent radical
      cystectomy and extended pelvic lymph node dissection for urothelial bladder
      cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled,
      including bilateral pelvic and common iliac, presacral and retroperitoneal. We
      evaluated pathological features, treatment outcomes and cancer specific survival
      in patients with or without lymph node positive disease in the presacral and
      retroperitoneal regions. RESULTS: A median of 37 lymph nodes (IQR 27-49) were
      removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had
      metastatic disease in the presacral or retroperitoneal region. Four patients (3%)
      had an isolated solitary positive lymph node in these 2 templates. Two-year
      overall survival in patients without vs with presacral/retroperitoneal lymph node
      positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In
      contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77)
      and 29% (95% CI 7-51), respectively (p = 0.02). CONCLUSIONS: A substantial
      proportion of patients have lymph node positive disease in the presacral and
      retroperitoneal regions, including some with isolated and/or solitary lymph node
      involvement. While the limited positive lymph node burden in these templates
      suggests a potential therapeutic role for extending the anatomical boundaries of
      lymph node dissection, patient survival was poor. Extended lymph node dissection
      provides important staging information but to our knowledge the therapeutic
      benefit has yet to be definitively proved.

PMID- 21849182
TI  - Most renal oncocytomas appear to grow: observations of tumor kinetics with active
      surveillance.
AB  - PURPOSE: We examined the growth of tissue proven renal oncocytoma on serial
      imaging to improve our understanding of its natural history. MATERIALS AND
      METHODS: We reviewed the charts of 69 patients with oncocytoma diagnosed by
      biopsy or surgery between 2004 and 2010. A total of 29 cases were managed by
      active surveillance for at least 12 months and had 3 or more imaging events.
      Tumor size was documented and the average tumor growth rate was calculated using
      a random coefficient model. Interaction terms were used to investigate
      correlations between variables of interest, including age at diagnosis, gender,
      symptom status, laterality, initial tumor size, surveillance duration and number
      of imaging events. RESULTS: At a mean surveillance duration of 40 months 80% of
      oncocytomas increased in size. Based on the random coefficient model the
      estimated average growth rate was 0.16 mm monthly (95% CI 0.097-0.228, p
      <0.0001). We identified no variables that significantly correlated with growth.
      CONCLUSIONS: Despite its low metastatic potential renal oncocytoma appears to
      progress locally with a growth rate similar to that of RCC. Thus, absent tumor
      growth on serial imaging is not a robust prognostic factor for benign histology.
      Biopsy remains the mainstay of diagnosis. At centers where it can be performed
      safely and accurately, active surveillance of tissue proven oncocytoma appears to
      be safe in the short term. Alternative management includes partial nephrectomy
      and minimally invasive approaches. To our knowledge this is the largest study of
      oncocytoma natural history.

PMID- 21849183
TI  - Super extended versus extended pelvic lymph node dissection in patients
      undergoing radical cystectomy for bladder cancer: a comparative study.
AB  - PURPOSE: There is evidence from retrospective studies that radical cystectomy
      with extended pelvic lymph node dissection provides better staging and outcomes
      than limited lymph node dissection. However, the optimal limits of extended lymph
      node dissection remain unclear. We compared oncological outcomes at 2 cystectomy
      centers where 2 different extended lymph node dissection templates are practiced
      to determine whether removing lymphatic tissue up to the inferior mesenteric
      artery confers an additional survival advantage. MATERIALS AND METHODS: Patients
      undergoing radical cystectomy and extended lymph node dissection with curative
      intent from 1985 to 2005 were included in analysis if they met certain criteria,
      including clinically organ confined urothelial bladder carcinoma (cN0M0),
      pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy.
      Survival and recurrence data were analyzed. RESULTS: Demographic data and
      pathological subgroup distribution (pT2 and pT3) were similar in the 554
      University of Southern California and 405 University of Bern patients. University
      of Southern California patients had higher median number of lymph nodes removed
      than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of
      lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern
      California and University of Bern groups had similar 5-year recurrence-free
      survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55
      and 0.44, respectively). The overall recurrence rate was equal at the 2
      institutions (38%). CONCLUSIONS: Meticulous extended lymph node dissection up to
      the mid-upper third of the common iliac vessels appears to provide survival and
      recurrence outcomes similar to those of a super extended template up to the
      inferior mesenteric artery. Complete skeletonization in the extended lymph node
      dissection template is more important than nodal yield. This does not exclude the
      possibility that certain patient subgroups with suspicious nodes or after
      neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

PMID- 21849184
TI  - Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves
      cancer detection following transrectal ultrasound biopsy and correlates with
      multiparametric magnetic resonance imaging.
AB  - PURPOSE: A novel platform was developed that fuses pre-biopsy magnetic resonance
      imaging with real-time transrectal ultrasound imaging to identify and biopsy
      lesions suspicious for prostate cancer. The cancer detection rates for the first
      101 patients are reported. MATERIALS AND METHODS: This prospective, single
      institution study was approved by the institutional review board. Patients
      underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil,
      which included T2-weighted, spectroscopic, dynamic contrast enhanced and
      diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for
      cancer were graded according to the number of sequences suspicious for cancer as
      low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard
      12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound
      fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging
      lesions. Chi-square and within cluster resampling analyses were used to correlate
      suspicion on magnetic resonance imaging and the incidence of cancer detected on
      biopsy. RESULTS: Mean patient age was 63 years old. Median prostate specific
      antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital
      rectal examination. Of patients with low, moderate and high suspicion on magnetic
      resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively
      (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected
      more cancer per core than standard 12-core transrectal ultrasound biopsy for all
      levels of suspicion on magnetic resonance imaging. CONCLUSIONS: Prostate cancer
      localized on magnetic resonance imaging may be targeted using this novel magnetic
      resonance imaging/ultrasound fusion guided biopsy platform. Further research is
      needed to determine the role of this platform in cancer detection, active
      surveillance and focal therapy, and to determine which patients may benefit.

PMID- 21849185
TI  - Complications and failure to rescue after laparoscopic versus open radical
      nephrectomy.
AB  - PURPOSE: Since to our knowledge the population level impact of laparoscopy on
      post-radical nephrectomy morbidity and mortality remains unknown, we compared the
      rates of postoperative complications and failure to rescue (the fatality rate in
      patients with a complication) in patients treated with laparoscopic vs open
      radical nephrectomy. MATERIALS AND METHODS: Using linked SEER (Surveillance,
      Epidemiology and End Results)-Medicare data we identified patients with kidney
      cancer who were treated with laparoscopic or open radical nephrectomy from 2000
      through 2005. After measuring the frequency of postoperative complications and
      failure to rescue we fit multivariate logistic regression models to estimate the
      association of these outcomes with surgical approach, adjusting for patient
      characteristics, cancer severity and surgery year. We also assessed the
      relationship between case volume, complications and failure to rescue. RESULTS:
      We identified 2,108 (26%) and 5,895 patients (74%) treated with laparoscopic and
      open radical nephrectomy, respectively. The overall rates of complications and
      failure to rescue were 36.9% and 5.3%, respectively. The predicted probability of
      any, major, medical and surgical complications was 15%, 12%, 13% and 23% lower,
      respectively, after laparoscopic than after open radical nephrectomy (each p
      <0.05). Despite less frequent complications patients treated with laparoscopic
      radical nephrectomy had a greater probability of failure to rescue (7.6% vs 4.6%,
      p = 0.010). Higher volume surgeons and hospitals had a lower rate of failure to
      rescue in patients treated with radical nephrectomy (each p <0.05) but not with
      open radical nephrectomy. CONCLUSIONS: Supporting the decreased morbidity of
      laparoscopy, patients treated with radical nephrectomy had fewer complications
      than those who underwent open radical nephrectomy. However, failure to rescue was
      more common in patients with a complication after radical nephrectomy, suggesting
      that these events may be more difficult to recognize and manage successfully,
      especially among less experienced surgeons and hospitals.

PMID- 21849186
TI  - Dutasteride reduces prostatitis symptoms compared with placebo in men enrolled in
      the REDUCE study.
AB  - PURPOSE: Men at risk for prostate cancer may concurrently experience chronic
      prostatitis or pelvic pain. We evaluated the effect of dutasteride on prostatitis
      like symptoms in the REDUCE study population. MATERIALS AND METHODS: REDUCE was a
      4-year, randomized, double-blind, placebo controlled study of prostate cancer
      risk reduction with 0.5 mg dutasteride vs placebo in men 50 to 75 years old with
      prostate specific antigen 2.5 to 10 ng/ml and a negative prostate biopsy in the
      previous 6 months. In this analysis we investigated change from baseline in
      Chronic Prostatitis Symptom Index in men with prostatitis-like pain (Chronic
      Prostatitis Symptom Index pain subscore 5 or greater) and prostatitis-like
      syndrome (perineal or ejaculatory pain plus Chronic Prostatitis Symptom Index
      pain subscore 4 or greater), the proportion of subjects with at least a moderate
      Chronic Prostatitis Symptom Index response (6-unit or greater improvement) and
      reports of new onset clinical prostatitis. RESULTS: Of 5,379 men with a total
      baseline Chronic Prostatitis Symptom Index score 678 (12.6%) had prostatitis-like
      pain and 427 (7.9%) had prostatitis-like syndrome. Chronic Prostatitis Symptom
      Index total score decreased significantly at 48 months in the dutasteride group
      vs placebo in men with prostatitis-like pain (p <0.0001) and with prostatitis
      like syndrome (t test p = 0.03). There were significantly more Chronic
      Prostatitis Symptom Index responders with dutasteride vs placebo in the
      prostatitis-like pain (49% vs 37%, respectively, p = 0.0033) and prostatitis-like
      syndrome (46% vs 35%, Fisher's exact test p = 0.0265) subgroups. Prostatitis was
      reported as an adverse event by significantly more men randomized to placebo
      (3.6%) than to dutasteride (2.5%, p = 0.003). CONCLUSIONS: Long-term dutasteride
      therapy resulted in improvement in prostatitis related symptoms in older men with
      an increased prostate specific antigen.

PMID- 21849187
TI  - Acute versus chronic exposure to androgen suppression for prostate cancer: impact
      on the exercise response.
AB  - PURPOSE: Exercise has been proposed as an effective countermeasure for androgen
      suppression therapy induced side effects. Since the magnitude of fat gain and
      muscle loss is most pronounced during the early phases of androgen suppression
      therapy, the exercise response may differ by the duration of androgen suppression
      therapy. We investigated whether the exercise response varied by the prior
      duration of exposure to androgen suppression therapy, that is acute--less than 6
      months vs later--6 months or greater. MATERIALS AND METHODS: A total of 50 men 55
      to 84 years old undergoing androgen suppression therapy for nonbone metastatic
      prostate cancer completed a progressive resistance and cardiovascular exercise
      program for 12 weeks, including 16 with acute and 34 with chronic androgen
      suppression therapy exposure. We assessed fat and lean mass by dual energy x-ray
      absorptiometry as well as muscle strength, functional performance, quality of
      life and blood biomarkers. RESULTS: Patients on acute androgen suppression showed
      an increase in total body fat compared to those on chronic androgen suppression
      (0.9 kg, p = 0.018). Each group experienced increased appendicular skeletal
      muscle (about 0.5 kg, p <0.01). Triglycerides decreased in the chronic group and
      increased in the acute group (p = 0.027). Change in triglycerides were associated
      with the change in total body fat (r = 0.411, p = 0.004). There were no
      differences between the groups in prostate specific antigen, testosterone,
      glucose, insulin, total cholesterol, low and high density lipoprotein,
      cholesterol, C-reactive protein, homocysteine or quality of life. The 2 groups
      showed similar improvement in muscle strength and function, and cardiovascular
      fitness. CONCLUSIONS: Apart from differences in body fat and triglycerides the
      beneficial effects of exercise are similar in patients on acute or chronic
      androgen suppression therapy.

PMID- 21849188
TI  - Intratumor C-reactive protein as a biomarker of prognosis in localized renal cell
      carcinoma.
AB  - PURPOSE: Serum C-reactive protein has been shown to have prognostic value in
      localized and metastatic renal cell carcinoma. However, the prognostic value of
      intratumor C-reactive protein remains unknown. MATERIALS AND METHODS: A total of
      95 patients with resected, clinically localized (T1-T4N0M0) clear cell renal cell
      carcinoma were followed postoperatively. Intratumor C-reactive protein expression
      was assessed in surgical specimens using immunohistochemical analysis. Patients
      were categorized by staining intensity into low risk (staining 0 to 1),
      intermediate risk (staining 2) and high risk (staining 3) groups. Kaplan-Meier
      and multivariate Cox regression analyses were used to examine overall survival
      across patient and disease characteristics. Variables examined in multivariate
      Cox regression analysis included T stage, Fuhrman nuclear grade, tumor size,
      preoperative serum C-reactive protein and intratumor C-reactive protein staining.
      RESULTS: Followup extended up to 46 months with a mean (SD) of 29.8 (11.0)
      months. Twelve patients (12.6%) died during followup. Of all tumors 49.5%, 25.3%
      and 25.3% were graded by intratumor C-reactive protein staining as low risk (0 to
      1), intermediate risk (2) and high risk (3), respectively. After controlling for
      variables significant on univariate analysis, patients in the high risk (3) group
      experienced a 27-fold increased risk of overall mortality compared to those in
      the low risk (0-1) group (HR 27.767, 95% CI 1.488-518.182). After adjusting for
      tumor staining, preoperative serum C-reactive protein was not a significant
      predictor of overall survival (p = 0.741). CONCLUSIONS: Intratumor C-reactive
      protein may be a robust biomarker of prognosis in patients with localized renal
      cell carcinoma.

PMID- 21849189
TI  - Implications of pacemakers and implantable cardioverter defibrillators in
      urological practice.
AB  - PURPOSE: Pacemakers and implantable cardioverter defibrillators are widely used
      and often encountered in urology practices worldwide. Safety and performance
      during electrosurgery, extracorporeal shock wave lithotripsy, magnetic resonance
      imaging, positron emission tomography and radiotherapy are not clearly defined.
      We reviewed the literature on their use and implications in urological practice.
      MATERIALS AND METHODS: We performed a PubMed(r) search and all relevant articles
      were studied to understand the basic functioning of these devices along with the
      technological advances designed to reduce electromagnetic interference. RESULTS:
      A modern permanent pacemaker is comprised of a generator and leads connecting to
      the atrial or ventricular myocardium with sensing and pacing functions.
      Implantable cardioverter defibrillators respond to episodes of ventricular
      tachycardia and fibrillation by discharging a defibrillating current. From a
      device perspective, several protective mechanisms have been developed in the
      permanent pacemaker/implantable cardioverter defibrillator to reduce the effects
      of electromagnetic interference. These involve generator material changes, lead
      modification, and better sensing and pacing algorithms. Magnetic resonance
      imaging compatible pacemakers have now been developed and are approved for use in
      Europe. From a urologist's perspective 5 procedures require the close monitoring
      of permanent pacemaker/implantable cardioverter defibrillator function. 1) For
      electrosurgery modifications in the device and in the methods of use have been
      recommended. 2) For extracorporeal shock wave lithotripsy the European
      Association of Urology provides some guidance with regard to patients with these
      devices. 3) During positron emission tomography the pulse generator and the lead
      area should be covered with lead to protect the device. 4) Magnetic resonance
      imaging is contraindicated but currently trials are under way for a new pacing
      system for safe use in the magnetic resonance imaging environment. 5) Patients
      can undergo radiotherapy with standard precautions but those with an abdominal
      permanent pacemaker/implantable cardioverter defibrillator require careful
      planning. Finally, implanted devices should have a full evaluation before and
      after the procedure. CONCLUSIONS: Clear guidelines are essential given the rapid
      advances in technology to enhance patient safety. Magnetic resonance imaging
      should be avoided in patients without a magnetic resonance imaging compatible
      device. However, patients can undergo extracorporeal shock wave lithotripsy,
      radiotherapy and positron emission tomography as long as the device is not in the
      path.

PMID- 21849190
TI  - Urodynamic testing in children: indications, technique, interpretation and
      significance.
AB  - PURPOSE: Urodynamic studies in children have been performed with increasing
      frequency as the techniques, reproducibility and reliability of the testing have
      been refined in the last quarter century. Children of all ages and with a variety
      of comorbidities are now often referred for urodynamic testing to evaluate and
      understand the causes of incontinence and/or persistence of lower urinary tract
      symptoms, as well as to appropriately define and evaluate treatment regimens.
      MATERIALS AND METHODS: We performed a MEDLINE(r) search for relevant articles on
      urinary tract dysfunction, neurogenic bladder and urodynamic studies in the
      pediatric population. We also included 3 major textbooks that addressed the
      subject matter. RESULTS: We review the current indications for urodynamic studies
      in children with nonneurogenic and neurogenic bladder dysfunction. We summarize
      the components and techniques of the current practice of urodynamic studies in
      the pediatric population, and explain how to identify abnormal results.
      CONCLUSIONS: The use of urodynamic studies in pediatrics has become almost
      mandatory for the effective management of severe or therapy resistant urinary
      tract abnormalities. This review may be used as a guideline for the appropriate
      application of urodynamics in this patient population.

PMID- 21849191
TI  - Impact of tumor size on renal function and prediction of renal insufficiency
      after radical nephrectomy in patients with renal cell carcinoma.
AB  - PURPOSE: From the perspective of oncological and functional outcomes partial
      nephrectomy is considered standard surgery for small renal tumors 4 cm or less.
      However, radical nephrectomy is commonly done for small tumors. It is important
      to predict postoperative renal function in patients to choose the most optimal
      surgical procedure. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 271 patients treated with radical nephrectomy for renal cell
      carcinoma. Associations of tumor size and clinical variables with renal function
      were analyzed. RESULTS: Preoperatively the mean +/- SD glomerular filtration rate
      was 74.38 +/- 17.70 ml per minute/1.73 m(2) and 56 patients (20%) had renal
      insufficiency (glomerular filtration rate less than 60 ml per minute/1.73 m(2)).
      The mean decrease in the glomerular filtration rate after radical nephrectomy was
      24.2 +/- 12.40 ml per minute/1.73 m(2) (31.5% +/- 15%). Of 215 patients with a
      preoperative glomerular filtration rate of 60 ml per minute/1.73 m(2) or greater
      165 (77%) had new onset renal insufficiency. Age, tumor size, preoperative
      glomerular filtration rate and hypertension were significantly associated with
      new onset renal insufficiency. Multivariate analysis revealed that age 60 years
      or greater, tumor size 7 cm or less and the preoperative glomerular filtration
      rate were independent risk factors for new onset renal insufficiency (p <0.05).
      Finally, we developed a predictive model for new onset renal insufficiency after
      radical nephrectomy. CONCLUSIONS: Tumor size 7 cm or less, age 60 years or
      greater and a decreased preoperative glomerular filtration rate were significant
      risk factors for new onset renal insufficiency in patients treated with radical
      nephrectomy. Partial nephrectomy might be considered an option according to the
      risk of postoperative renal insufficiency, especially in elderly patients with a
      tumor of 7 cm or less.

PMID- 21849192
TI  - Increasing use of kidney sparing approaches for localized renal tumors in a
      community based health system: impact on renal functional outcomes.
AB  - PURPOSE: The use of partial nephrectomy and other kidney sparing approaches in
      national databases lags far behind practice patterns at major academic centers.
      The reasons and impact of this disparity are largely unknown. We examined the
      trend in kidney sparing approaches in a community based health care system to
      examine associated factors and impact on renal function. MATERIALS AND METHODS:
      We evaluated the records of all patients who underwent intervention for
      suspicious renal lesions at a single health care system between 1998 and 2010.
      Demographic, pathological and functional data were collected in an institutional
      review board approved database. RESULTS: During the 12 study years a kidney
      sparing approach was used in 35% of patients with localized renal tumors. A clear
      increase in the proportion of patients undergoing a kidney sparing approach was
      observed, including 11%, 23% and 49% during successive 4-year periods. A kidney
      sparing approach was used in 81% of patients with tumors 4 cm or less during 2009
      to 2010. Although high volume (greater than 20 cases annually), more recently
      graduating (2001 or later) and fellowship trained surgeons had higher kidney
      sparing approach use overall (each p <0.03), the proportion of patients who
      underwent a kidney sparing approach increased with time in all study groups (p
      <0.0001). The renal functional loss in patients who underwent a kidney sparing
      approach and radical nephrectomy was 2% and 30%, respectively (p <0.001).
      CONCLUSIONS: The kidney sparing approach rate in a community based health care
      system can approach rates at major academic centers. This practice pattern
      appears related to the addition of recent graduates and urological oncologists
      but also to a change in long-standing practice patterns of other community
      urologists. These data suggest that the use of kidney sparing approaches
      nationwide and the associated renal functional benefits may continue to increase.

PMID- 21849193
TI  - Serum amino acid levels as a biomarker for renal cell carcinoma.
AB  - PURPOSE: Prognosis in renal cell carcinoma is dependent on tumor stage at
      presentation, with significant differences in survival between early and late
      stage disease. Currently to our knowledge no screening tests or biomarkers have
      been identified for the early detection of kidney cancer. Therefore, we
      investigated whether serum amino acid profiles are a potentially useful biomarker
      in patients with renal cell carcinoma. MATERIALS AND METHODS: The concentrations
      of 26 amino acids were determined in serum taken preoperatively from 189 patients
      with renal cell carcinoma, and from 104 age and sex matched controls. RESULTS:
      Statistically significant changes were observed in patient levels of 15 amino
      acids, with 13 being decreased and 2 being increased. A logistic regression model
      using 8 amino acids including cysteine, ornithine, histidine, leucine, tyrosine,
      proline, valine and lysine was created to distinguish cases from controls. A
      receiver operator curve based on this model had an area under the curve of 0.81.
      This same model also had predictive value in terms of overall survival and tumor
      recurrence in patients with renal cell carcinoma. CONCLUSIONS: Our findings
      suggest that serum amino acid levels may be useful as a screening tool for the
      identification of individuals with renal cell carcinoma and the prediction of
      outcomes.

PMID- 21849194
TI  - Using wound drains for the uncomplicated penile prosthesis.

PMID- 21849195
TI  - Safety and errors: a lesson from the airlines.

PMID- 21849196
TI  - Concordance and prediction ability of original and reviewed vascular invasion and
      other prognostic parameters of clinical stage I nonseminomatous germ cell
      testicular tumors after retroperitoneal lymph node dissection.
AB  - PURPOSE: We reviewed the slides of patients with clinical stage I nonseminomatous
      germ cell testicular tumors who underwent retroperitoneal lymph node dissection
      to evaluate the concordance between original and reviewed vascular invasion
      status, and other histological correlates. MATERIALS AND METHODS: Between 2002
      and 2007 at our institution 202 consecutive patients underwent retroperitoneal
      lymph node dissection. We requested the slides of 183 patients who underwent
      orchiectomy elsewhere. The risk of nodal metastasis was considered high in those
      with vascular invasion and/or greater than 90% embryonal carcinoma, and low in
      those with no vascular invasion and embryonal carcinoma less than 90%. Using
      Cohen's kappa we assessed the concordance index between original and reviewed
      parameters (vascular invasion and risk category). Using the chi-square test we
      also evaluated the association between nodal status at retroperitoneal lymph node
      dissection and original vs reviewed parameters. RESULTS: The original report did
      not contain vascular invasion information on 98 of 183 cases (53.4%). A total of
      164 patients were evaluable since we had no slides for 19. Vascular invasion
      absence and presence were confirmed in 27 (73.0%) and 30 (78.9%) of 37 patients,
      respectively (Cohen's kappa = 0.16). Low and high risk status was confirmed in 20
      of 28 patients (71.4%) and in 47 of 64 (50.6%), respectively (Cohen's kappa =
      0.22). Reviewed vascular invasion and risk category were significantly associated
      with nodal status at retroperitoneal lymph node dissection (chi-square test p =
      0.03 and 0.01, respectively), although the original parameters were not.
      CONCLUSIONS: In half of the patients no information was available on vascular
      invasion in the original reports. Concordance between original and reviewed
      reports was generally poor. Reviewed parameters better predicted nodal status at
      retroperitoneal lymph node dissection. These findings may have important
      implications in clinical practice.

PMID- 21849197
TI  - Can a durable disease-free survival be achieved with surgical resection in
      patients with pathological node positive renal cell carcinoma?
AB  - PURPOSE: Patients with isolated regional nodal metastases from renal cell
      carcinoma are a distinct cohort for which resection of involved lymph nodes may
      be therapeutic. We assessed the outcomes of patients treated at our institution
      with pathological node positive renal cell carcinoma without concomitant
      metastatic disease (T(any)N+M0). MATERIALS AND METHODS: A total of 2,521 patients
      with nonmetastatic renal cell carcinoma (T(any)N(any)M0) of any histological
      subtype treated with nephrectomy were identified between 1995 and 2009.
      Pathological regional node positive disease in the absence of clinically
      detectable metastases (T(any)N(1-2)M0) was present in 68 patients (2.7%) and
      these patients formed our study cohort. Patients were assessed for timing and
      location of recurrence, disease specific survival and overall survival.
      Multivariate Cox regression analysis was performed to define factors predictive
      of recurrence and overall survival. RESULTS: Of the 68 patients with T(any)N(1
      2)M0 renal cell carcinoma 22.1% were free of disease at a median followup of 43.5
      months. In those patients experiencing recurrence, disease was detected within
      the first 4 months after surgery in 51% and was most commonly detected at
      multiple organ sites. The Kaplan-Meier estimated 5-year overall survival and
      disease specific survival was 37% and 39%, respectively. Predictors of a
      favorable outcome included an Eastern Cooperative Oncology Group performance
      status of 0, single node involvement, absence of sarcomatoid features and
      papillary histology. CONCLUSIONS: Nephrectomy with lymph node dissection can
      provide a durable disease-free survival in a proportion of patients with
      regionally advanced renal cell carcinoma and limited lymph node metastases.

PMID- 21849198
TI  - A randomized trial comparing 2 doses of polidocanol sclerotherapy for hydrocele
      or spermatocele.
AB  - PURPOSE: Polidocanol sclerotherapy for hydrocele or spermatocele combines high
      efficiency with low morbidity, but the optimal dose is not known. We compared the
      efficacy and morbidity of 2 or 4 ml polidocanol sclerotherapy for hydrocele or
      spermatocele. MATERIALS AND METHODS: From 1993 to 2005 a double-blind randomized
      clinical trial was conducted using 2 or 4 ml polidocanol (30 mg/ml) for
      sclerotherapy of hydrocele/spermatocele in 224 evaluable patients at 3 university
      hospitals. Fluid was evacuated and 2 or 4 ml polidocanol was administered by a
      nurse, with the amount injected concealed from others present. At 3-month
      followup morbidity was ascertained using a questionnaire completed by the
      patients. Fluid recurrence was determined clinically and generally re-treated.
      RESULTS: After the first treatment, cure was observed in 59% and 47% in the 4 and
      the 2 ml group, respectively (p = 0.04). More patients in the 4 ml group had
      complications (31% vs 18%, p = 0.04). Complications were mostly of low or
      moderate intensity and seldom required medication. After 1 to 4 treatments 200 of
      224 patients (89%) were cured and another 10 (5%) had small amounts of residual
      fluid, with no difference between the groups. Of the patients with
      hydroceles/spermatoceles larger than 175 ml, 58% and 34% were cured after the
      first treatment in the 4 and 2 ml groups, respectively (p = 0.012), with no
      differences in complications between the groups. CONCLUSIONS: Polidocanol
      sclerotherapy was effective for the treatment of hydrocele or spermatocele in our
      patients, with 94% satisfactory results after 1 to 4 treatments. A dose of 4 ml
      was superior to 2 ml, particularly for larger hydroceles/spermatoceles.

PMID- 21849199
TI  - Deciphering the genetics of male infertility: progress and challenges.

PMID- 21849200
TI  - A multidisciplinary evaluation of inter-reviewer agreement of the nephrometry
      score and the prediction of long-term outcomes.
AB  - PURPOSE: The nephrometry score was introduced in 2009 as a way to quantify renal
      tumor complexity in a systematic way. However, the reproducibility of scoring has
      not been rigorously validated across specialty or level of training, nor has it
      been evaluated with regard to meaningful clinical outcomes. MATERIALS AND
      METHODS: We identified 95 consecutive patients with a solid renal mass treated
      surgically. Each renal tumor was separately scored by 6 reviewers, including 2
      staff urologists, 1 staff radiologist, 2 trainees (1 urology, 1 radiology) and 1
      medical student. Inter-reviewer agreement for nephrometry score was evaluated
      using Lin's concordance correlation coefficient. We evaluated the ability of the
      nephrometry score to predict surgery type, pathological features and clinical
      outcomes. RESULTS: Agreement in nephrometry score was substantial among the 3
      staff physicians (0.72, 95% CI 0.64-0.80). Nephrometry score agreement continued
      to be substantial when including the trainees and medical student in the analysis
      (0.75, 95% CI 0.69-0.81). The median nephrometry score of patients treated with
      radical nephrectomy was 9.0 vs 7.2 for those treated with a nephron sparing
      approach (p <0.001). Increasing nephrometry score was associated with increased
      risk of distant metastasis (HR 3.27, p <0.001), death from renal cell carcinoma
      (HR 2.83, p <0.001) and death from any cause (HR 1.24, p = 0.017). CONCLUSIONS:
      Nephrometry scoring with minimal initial instruction was robust across
      specialties and levels of training. The additional anatomical information that
      nephrometry score adds to size alone may be associated with other important
      clinical outcomes such as tumor aggressiveness and survival, and warrants further
      study.

PMID- 21849201
TI  - Increased risk of overall and cardiovascular mortality after radical nephrectomy
      for renal cell carcinoma 2 cm or less.
AB  - PURPOSE: We used a large, population based registry to assess whether a
      difference in overall and cardiovascular survival may exist between radical
      nephrectomy and partial nephrectomy for renal cell carcinoma 2 cm or less.
      MATERIALS AND METHODS: From the SEER (Surveillance, Epidemiology and End Results)
      registry we identified 4,216 patients with histologically confirmed renal cell
      carcinoma 2 cm or less who were treated with partial or radical nephrectomy.
      Patient and tumor characteristics were compared between the 2 patient groups.
      Multivariate logistic regression was done to predict the odds of undergoing
      radical nephrectomy. Cardiovascular survival and overall survival were compared
      between the 2 cohorts, adjusting for patient and tumor characteristics. RESULTS:
      Overall 2,301 patients (55%) underwent partial nephrectomy. Partial nephrectomy
      use steadily increased during the study period from 27% of all cases in 1998 to
      66% in 2007. Patients who underwent partial nephrectomy were an average of 2.5
      years younger than those treated with radical nephrectomy (56.4 vs 58.9 years, p
      <0.001). They were more likely to be white and from the western or northeastern
      United States. Older age was the only independent predictor of radical
      nephrectomy (OR 1.02, 95% CI 1.01-1.03). When controlling for patient
      characteristics and surgery year, radical nephrectomy was associated with worse
      overall mortality (HR 2.24, 95% CI 1.75-2.84) and cardiovascular mortality (HR
      2.53, 95% CI 1.51-4.23). CONCLUSIONS: Radical nephrectomy is associated with
      worse overall and cardiovascular survival compared to partial nephrectomy in
      patients with localized renal cell carcinoma 2 cm or less. These findings justify
      the widespread application of nephron sparing techniques to treat localized
      kidney cancer.

PMID- 21849202
TI  - Complementation studies with the novel "Bungowannah" virus provide new insights
      in the compatibility of pestivirus proteins.
AB  - In recent years several atypical pestiviruses have been described. Bungowannah
      virus is the most divergent virus in this group. Therefore, heterologous
      complementation was used to clarify the phylogenetic relationship and to analyze
      the exchangeability of genome regions encoding structural proteins. Using a BVDV
      type 1 backbone, chimeric constructs with substituted envelope proteins E(rns),
      E1 and E2, were investigated. While all constructs replicated autonomously,
      infectious high titer chimeric virus could only be observed after exchanging the
      complete E1-E2 encoding region. The complementation of E1 and E2 alone resulted
      only in replicons. Complementation of BVDV-E(rns) was only efficient if
      Bungowannah virus-E(rns) was expressed from a bicistronic construct. Our data
      provide new insights in the compatibility of pestivirus proteins and demonstrate
      that heterologous complementation could be useful to characterize new
      pestiviruses.

PMID- 21849203
TI  - Removal of organics and nutrients from food wastewater using combined
      thermophilic two-phase anaerobic digestion and shortcut biological nitrogen
      removal.
AB  - A process combining pilot-scale two-phase anaerobic digestion and shortcut
      biological nitrogen removal (SBNR) was developed to treat organics and nutrients
      (nitrogen and phosphorus) from food wastewater. The thermophilic two-phase
      anaerobic digestion process was investigated without adjusting the pH of the
      wastewater for the pre-acidification process. The digested food wastewater was
      treated using the SBNR process without supplemental carbon sources or alkalinity.
      Under these circumstances, the combined system was able to remove about 99% of
      COD, 88% of TN, and 97% of TP. However, considerable amounts of nutrients were
      removed due to chemical precipitation processes between the anaerobic digestion
      and SBNR. The average TN removal efficiency of the SBNR process was about 74% at
      very low C/N (TCOD/TN) ratio of 2. The SBNR process removed about 39% of TP from
      the digested food wastewater. Conclusively, application of the combined system
      improved organic removal efficiency while producing valuable energy (biogas),
      removed nitrogen at a low C/N ratio, and conserved additional resources (carbon
      and alkalinity).

PMID- 21849204
TI  - Estimating municipal solid waste generation by different activities and various
      resident groups: a case study of Beijing.
AB  - Reliable and accurate determinations of the quantities and composition of wastes
      is required for the planning of municipal solid waste (MSW) management systems. A
      model, based on the interrelationships of expenditure on consumer goods, time
      distribution, daily activities, residents groups, and waste generation, was
      developed and employed to estimate MSW generation by different activities and
      resident groups in Beijing. The principle is that MSW is produced by consumption
      of consumer goods by residents in their daily activities: 'Maintenance' (meeting
      the basic needs of food, housing and personal care), 'Subsistence' (providing the
      financial requirements) and 'Leisure' (social and recreational pursuits)
      activities. Three series of important parameters - waste generation per unit of
      consumer expenditure, consumer expenditure distribution to activities in unit
      time, and time assignment to activities by different resident groups - were
      determined using a statistical analysis, a sampling survey and the Analytic
      Hierarchy Process, respectively. Data for analysis were obtained from the Beijing
      Statistical Yearbook (2004-2008) and questionnaire survey. The results reveal
      that 'Maintenance' activity produced the most MSW, distantly followed by
      'Leisure' and 'Subsistence' activities. In 2008, in descending order of MSW
      generation the different resident groups were floating population, non-civil
      servants, retired people, civil servants, college students (including both
      undergraduates and graduates), primary and secondary students, and preschoolers.
      The new estimation model, which was successful in fitting waste generation by
      different activities and resident groups over the investigated years, was
      amenable to MSW prediction.

PMID- 21849205
TI  - Effects of biologically-active chemical mixtures on fish in a wastewater-impacted
      urban stream.
AB  - Stream flow in urban aquatic ecosystems often is maintained by water-reclamation
      plant (WRP) effluents that contain mixtures of natural and anthropogenic
      chemicals that persist through the treatment processes. In effluent-impacted
      streams, aquatic organisms such as fish are continuously exposed to biologically
      active chemicals throughout their life cycles. The North Shore Channel of the
      Chicago River (Chicago, Illinois) is part of an urban ecosystem in which >80% of
      the annual flow consists of effluent from the North Side WRP. In this study,
      multiple samplings of the effluent and stream water were conducted and fish
      (largemouth bass and carp) were collected on 2 occasions from the North Shore
      Channel. Fish also were collected once from the Outer Chicago Harbor in Lake
      Michigan, a reference site not impacted by WRP discharges. Over 100 organic
      chemicals with differing behaviors and biological effects were measured, and 23
      compounds were detected in all of the water samples analyzed. The most frequently
      detected and highest concentration (>100MUg/L) compounds were
      ethylenediaminetetraacetic acid and 4-nonylphenolmono-to-tetraethoxycarboxylic
      acids. Other biologically-active chemicals including bisphenol A, 4-nonylphenol,
      4-nonylphenolmono-to-tetraethoxylates, 4-tert-octylphenol, and 4-tert
      octylphenolmono-to-tetraethoxylates were detected at lower concentrations
      (<5MUg/L). The biogenic steroidal hormones 17beta-estradiol, estrone,
      testosterone, 4-androstene-3,17-dione, and cis-androsterone were detected at even
      lower concentrations (<0.005MUg/L). There were slight differences in
      concentrations between the North Side WRP effluent and the North Shore Channel,
      indicating minimal in-stream attenuation. Fish populations are continuously
      exposed to mixtures of biologically-active chemicals because of the relative
      persistency of the chemicals with respect to stream hydraulic residence time, and
      the lack of a fresh water source for dilution. The majority of male fish
      exhibited vitellogenin induction, a physiological response consistent with
      exposure to estrogenic compounds. Tissue-level signs of reproductive disruption,
      such as ovatestis, were not observed.

PMID- 21849206
TI  - Persistent high factor VIII activity leading to increased thrombin generation - a
      prospective cohort study.
AB  - INTRODUCTION: A persistently elevated level of factor VIII (FVIII) is an
      independent risk factor for venous thromboembolism (VTE). Although the
      pathophysiology of VTE is unclear, the involvement of thrombin generation (TG)
      has been postulated. Consequently this study was designed to (i) investigate the
      relationships between FVIII, Thrombin generation test (TGT) parameters and D
      dimer in VTE patients, (ii) determine whether elevated levels of FVIII and
      increased TG in these patients are transient or sustained. PATIENTS AND METHODS:
      After an initial period of anticoagulation had been completed 91 VTE patients and
      52 healthy controls were recruited. FVIII levels were determined by one-stage
      clotting (FVIII:C) and chromogenic (FVIII:Ch) assays. The potential to generate
      thrombin was measured using the Calibrated Automated Thrombogram (CAT) and D
      Dimer was by immuno-turbidometric assay. RESULTS: Patients' FVIII:C levels and
      FVIII:Ch, exhibited good agreement (rs=0.94; p<0.0001), although FVIII:C
      exhibited a mean bias of -6%. FVIII:Ch show a significant correlation with TGT
      Peak Thrombin (rs=0.30; p=0.004) and Peak Thrombin was found to be significantly
      higher (p=0.04) in patients with FVIII>200 iu/dL. Furthermore elevated levels of
      FVIII and increased thrombin generation parameters appeared to be consistent over
      time. CONCLUSION: Our data suggests that high FVIII leading to increased TG
      confers a significant risk of recurrent VTE and therefore we speculate that these
      patients may benefit from prolonged anticoagulation therapy.

PMID- 21849207
TI  - Determination of alpha-2-macroglobulin complexes by a new immuno-activity assay.
AB  - INTRODUCTION: Alpha-2-macroglobulin (alpha(2)M) is a broad specificity protease
      inhibitor which impacts several hemostatic pathways. Selective detection of
      various alpha(2)M complexes may be useful to define markers for the status of
      different hemostatic components. We present proof of principle for a novel assay
      to quantitatively measure alpha(2)M in complex with a variety of hemostatic
      factors. MATERIALS AND METHODS: The assay makes use of the fact that alpha(2)M
      entraps proteases within a molecular "cage", leaving them inaccessible to
      macromolecular substrates while retaining functionality against small synthetic
      substrates. Wells coated with anti-alpha(2)M antibodies were used to isolate the
      complexes from buffer or plasma, followed by detection of specific proteases with
      chromogenic substrates. Macromolecular inhibitors were added to eliminate signal
      from any unbound proteases. RESULTS: Calibration curves constructed with purified
      protease-alpha(2)M complexes were sigmoidal in nature, as is typical with immuno
      assays. The specificity of signal production was confirmed with inhibitors that
      target either free protease, or both free and alpha(2)M-bound protease. The
      detection range of the assay was dependent on the protease being measured, and
      the surrounding matrix. Interference in detection of complexes in plasma was
      found to be caused, in part, by free alpha(2)M. Thrombin-alpha(2)M complexes were
      quantified in adult and newborn plasma following induction of thrombin generation
      and found to be significantly higher in adults, likely due to higher prothrombin
      levels. CONCLUSIONS: This assay provides a versatile platform method for
      quantification of multiple protease-alpha(2)M complexes. It may prove useful for
      mechanistic in vitro studies of hemostatic pathways, and potentially for clinical
      applications.

PMID- 21849208
TI  - Individuation of female adolescents: relations with adolescents' perceptions of
      maternal behavior and with adolescent-mother discrepancies in perceptions.
AB  - The study examined how individuality and connectedness of female adolescents
      relate to their perceptions of maternal behavior and to adolescent-mother
      discrepancies in perceptions of maternal behavior. Seventy 16.5-year-old
      daughters and their mothers participated in the study. Individuality and
      connectedness of the daughters were assessed from observed daughter-mother
      interactions. The perceptions of daughters and mothers regarding maternal
      behavior were assessed using a video recall procedure. Daughters' negative
      perceptions of maternal behavior were associated with higher individuality.
      Daughter-mother discrepancies in perceptions of maternal behavior were related to
      lower connectedness of the daughters. Finally, daughters who showed high
      individuality at the expense of connectedness had more discrepancies in
      perceptions with their mothers compared to daughters that balanced between
      moderate-to-high individuality and connectedness. These findings underscore the
      importance of assessing daughters and mothers' perceptions of their interactions
      at the individual as well as the dyadic levels for understanding daughters'
      behavior during communication with their mothers.

PMID- 21849209
TI  - The need for additional metrics to assess therapeutic equivalence of some
      multiphasic modified-release products.
AB  - BACKGROUND: Advisory committees for the regulatory agencies of the United States
      (US Food and Drug Administration [FDA]) and Canada (Health Canada) recently
      considered issues associated with the determination of bioequivalence for some
      multiphasic modified-release (MR) drug products. The FDA has concluded that
      because of the complicated properties of some multiphasic MR products, additional
      metrics such as partial AUC are required for their assessment, whereas an
      advisory panel of Health Canada has decided that the current metrics are adequate
      and sufficient. POSITION STATEMENT: The authors agree with the conclusion of the
      FDA that additional metrics are required. DISCUSSION: The rationales considered
      by the advisory committees are discussed and commented upon. It is suggested that
      without applying an additional metric such as partial AUC, some multiphasic MR
      drug products might falsely be assumed to be therapeutically equivalent and
      unexpected clinical effects may occur.

PMID- 21849210
TI  - Alendronate and raloxifene use related to cardiovascular diseases:
      differentiation by different dosing regimens of alendronate.
AB  - BACKGROUND: Bisphosphonates are the class of medication used most widely to treat
      osteoporosis. Since an article reported that patients who used zoledronic acid, a
      bisphosphonate, had a higher proportion of atrial fibrillation (AF) in 2007, the
      issue of bisphosphonates and AF has become a growing concern. Due to the
      widespread use of bisphosphonates, it is necessary to explore the relationship
      between bisphosphonates and AF and other cardiovascular diseases. OBJECTIVE: We
      aimed to investigate the risk of AF, stroke, or acute myocardial infarction (AMI)
      associated with the use of the bisphosphonates alendronate and raloxifene in
      patients with osteoporosis. We also focused our analysis on the impact of
      different dosing regimens of alendronate. METHODS: The National Health Insurance
      Research Database was used to conduct an 8-year, population-based, retrospective
      cohort study. The study population comprised women who first took alendronate or
      raloxifene between 2002 and 2006 and who had a history of osteoporosis and
      vertebral or spinal fracture. Follow-up was conducted for every patient until the
      first diagnosis of AF, stroke, or AMI or until the end of the 1-year follow-up
      period. The Cox proportional hazards model was used to evaluate the association
      between the risk of cardiovascular disease and the prescription of alendronate or
      raloxifene. RESULTS: We identified 9609 women who had been prescribed either
      alendronate (n = 6949) or raloxifene (n = 2660). The patients treated with
      alendronate were at a lower risk of AF, stroke, or AMI compared with the
      raloxifene group (AF: hazard ratio [HR] = 0.60 [95% CI, 0.42-0.85]; stroke: HR =
      0.47 [95% CI, 0.39-0.57]; AMI: HR = 0.51 [95% CI, 0.36-0.72]). However, when
      analyzing the groups by different alendronate dosing regimens, those patients who
      received alendronate 10 mg had a significantly higher risk of AF and stroke
      compared with patients who received raloxifene (AF: HR = 1.66 [95% CI, 1.12
      2.46]; stroke: HR = 1.56 [95% CI, 1.23-1.98]). The alendronate 70-mg group
      demonstrated a lower risk of cardiovascular disease, be it AF, stroke, or AMI
      (AF: HR = 0.28 [95% CI, 0.18-0.43]; stroke: HR = 0.23 [95% CI, 0.18-0.30]; AMI:
      HR = 0.28 [95% CI, 0.18-0.41]). When we assigned alendronate 10 mg as the
      reference group, the alendronate 70 mg group had a lower risk of 3 cardiovascular
      diseases (AF: HR = 0.17 [95% CI, 0.10-0.27]; stroke: HR = 0.16 [95% CI, 0.12
      0.22]; AMI: HR = 0.21 [95% CI, 0.13-0.35]). CONCLUSIONS: Alendronate 10 mg was
      associated with a higher risk of cardiovascular disease than alendronate 70 mg.
      Further studies are required to investigate this relationship.

PMID- 21849211
TI  - Laser trabeculoplasty for open-angle glaucoma: a report by the american academy
      of ophthalmology.
AB  - OBJECTIVE: To provide an evidence-based summary of the outcomes, repeatability,
      and safety of laser trabeculoplasty for open-angle glaucoma. METHODS: A search of
      the peer-reviewed literature in the PubMed and the Cochrane Library databases was
      conducted in June 2008 and was last repeated in March 2010 with no date or
      language restrictions. The search yielded 637 unique citations, of which 145 were
      considered to be of possible clinical relevance for further review and were
      included in the evidence analysis. RESULTS: Level I evidence indicates an
      acceptable long-term efficacy of initial argon laser trabeculoplasty for open
      angle glaucoma compared with initial medical treatment. Among the remaining
      studies, level II evidence supports the efficacy of selective laser
      trabeculoplasty for lowering intraocular pressure for patients with open-angle
      glaucoma. Level III evidence supports the efficacy of repeat use of laser
      trabeculoplasty. CONCLUSIONS: Laser trabeculoplasty is successful in lowering
      intraocular pressure for patients with open-angle glaucoma. At this time, there
      is no literature establishing the superiority of any particular form of laser
      trabeculoplasty. The theories of action of laser trabeculoplasty are not
      elucidated fully. Further research into the differences among the lasers used in
      trabeculoplasty, the repeatability of the procedure, and techniques of treatment
      is necessary. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may
      be found after the references.

PMID- 21849212
TI  - Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts
      observed in astronauts after long-duration space flight.
AB  - PURPOSE: To describe the history, clinical findings, and possible etiologies of
      ophthalmic findings discovered in 7 astronauts after long-duration space flight,
      and document vision changes in approximately 300 additional astronauts. DESIGN:
      Retrospective, observational examination of ophthalmic findings in 7 astronauts
      and analysis of postflight questionnaires regarding in-flight vision changes in
      approximately 300 additional astronauts. PARTICIPANTS: Seven astronauts with
      ophthalmic anomalies upon return from long-duration space missions to the
      International Space Station and 300 additional astronauts who completed
      postflight questionnaires regarding in-flight vision changes. METHODS: Before and
      after long-duration space flight, all 7 subjects underwent complete eye
      examinations, including cycloplegic and/or manifest refraction and fundus
      photography. Six underwent postmission optical coherence tomography (OCT) and
      magnetic resonance imaging (MRI); 4 had lumbar punctures (LP). Approximately 300
      astronauts were queried regarding visual changes during space missions. MAIN
      OUTCOME MEASURES: Refractive change, fundus photograph examination, retina OCT,
      orbital MRI, LP opening pressures, and examination of visual acuity data.
      RESULTS: After 6 months of space flight, 7 astronauts had ophthalmic findings,
      consisting of disc edema in 5, globe flattening in 5, choroidal folds in 5,
      cotton wool spots (CWS) in 3, nerve fiber layer thickening by OCT in 6, and
      decreased near vision in 6 astronauts. Five of 7 with near vision complaints had
      a hyperopic shift >=+0.50 diopters (D) between pre/postmission spherical
      equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 showed
      globe flattening on MRI. Lumbar punctures performed in the 4 with disc edema
      documented opening pressures of 22, 21, 28, and 28.5 cm H(2)O performed 60, 19,
      12, and 57 days postmission, respectively. The 300 postflight questionnaires
      documented that approximately 29% and 60% of astronauts on short and long
      duration missions, respectively, experienced a degradation in distant and near
      visual acuity. Some of these vision changes remain unresolved years after flight.
      CONCLUSIONS: We hypothesize that the optic nerve and ocular changes we describe
      may result from cephalad fluid shifts brought about by prolonged microgravity
      exposure. The findings we report may represent parts of a spectrum of ocular and
      cerebral responses to extended microgravity exposure. FINANCIAL DISCLOSURE(S):
      The authors have no proprietary or commercial interest in any of the materials
      discussed in this article.

PMID- 21849213
TI  - State dependent posterior hippocampal volume increases in patients with major
      depressive disorder.
AB  - BACKGROUND: The hippocampal formation has been implicated in etiology and therapy
      response in major depressive disorder (MDD). However, prospective longitudinal
      studies investigating volumes in hippocampal subregions and their association
      with clinical findings are still lacking. METHODS: Global and regional
      hippocampal volumes and neuropsychological performance were assessed
      longitudinally in 15 young patients with unipolar early onset MDD who responded
      to therapy and 13 matched healthy control subjects. RESULTS: Although volumes at
      baseline did not differ between groups, patients with MDD showed significant
      posterior hippocampal volume increases during the treatment course (mean
      observation period 161.4 +/- 58.6 days). Posterior hippocampal volume increases
      were seen in every single patient. The detected posterior hippocampal volume
      increases were significantly correlated with the number of solved problems in a
      planning task at baseline. LIMITATIONS: The study is limited by the small sample
      size. Moreover, future studies should include patients who do not respond to
      antidepressant treatment. CONCLUSION: Patients with MDD showed selective
      increases in posterior hippocampal volumes which were not correlated to the
      degree of functional restitution. However, posterior hippocampal volume increases
      might constitute a surrogate parameter of neuroplasticity taking place during
      antidepressant therapy which might be predicted by executive functioning at
      baseline.

PMID- 21849214
TI  - Binge eating in binge eating disorder: a breakdown of emotion regulatory process?
AB  - Current explanatory models for binge eating in binge eating disorder (BED) mostly
      rely on models for bulimia nervosa (BN), although research indicates different
      antecedents for binge eating in BED. This study investigates antecedents and
      maintaining factors in terms of positive mood, negative mood and tension in a
      sample of 22 women with BED using ecological momentary assessment over a 1-week.
      Values for negative mood were higher and those for positive mood lower during
      binge days compared with non-binge days. During binge days, negative mood and
      tension both strongly and significantly increased and positive mood strongly and
      significantly decreased at the first binge episode, followed by a slight though
      significant, and longer lasting decrease (negative mood, tension) or increase
      (positive mood) during a 4-h observation period following binge eating. Binge
      eating in BED seems to be triggered by an immediate breakdown of emotion
      regulation. There are no indications of an accumulation of negative mood
      triggering binge eating followed by immediate reinforcing mechanisms in terms of
      substantial and stable improvement of mood as observed in BN. These differences
      implicate a further specification of etiological models and could serve as a
      basis for developing new treatment approaches for BED.

PMID- 21849215
TI  - The SHARP trial: lessons learnt; answers and more questions!

PMID- 21849216
TI  - Outgrowth inhibition of Clostridium beijerinckii spores by a bacteriocin
      producing lactic culture in ovine milk cheese.
AB  - In the manufacture of model cheeses, ovine milk was deliberately contaminated
      with spores of Clostridium beijerinckii INIA 63, a wild isolate from Manchego
      cheese with late blowing defect, and inoculated with nisin- and lacticin 481
      producing Lactococcus lactis subsp. lactis INIA 415 as starter, to test its
      potential to prevent the late blowing defect, or with L. lactis subsp. lactis
      INIA 415-2, a spontaneous mutant not producing bacteriocins. Cheeses made
      individually with the lactococcal strains, without clostridial spores, served as
      controls. Cheese made with clostridial spores and L. lactis subsp. lactis INIA
      415-2 showed late blowing defect after 120days of ripening. Spoilt cheese also
      showed lower concentrations of lactic acid, and higher levels of acetic,
      propionic and butyric acids, and of other volatile compounds such as 2-propanol
      and 1-butanol, than control cheese. In addition, cheese made with the bacteriocin
      producer did not show any late blowing symptoms, despite its spore counts similar
      to those of blown cheese, pointing to outgrowth inhibition of C. beijerinckii
      spores by bacteriocins. Besides, cheese made with the bacteriocin producer showed
      similar concentrations of lactic acid and volatile compounds than control cheese.
      Inclusion of L. lactis subsp. lactis INIA 415 in starter cultures seems a
      feasible method to prevent late blowing defect in cheese without altering its
      sensory characteristics.

PMID- 21849217
TI  - Culture-independent detection of microorganisms in traditional Slovakian bryndza
      cheese.
AB  - In order to investigate the microflora of Slovakian bryndza cheese (a cheese
      containing unpasteurized or pasteurized ewes' milk component) by a culture
      independent method, DNA was extracted directly from 7 bryndza samples and
      analysed by an innovative method. Using the universal prokaryotic and fungal
      primers, ribosomal DNA internal transcribed spacer (ITS) regions with variable
      length were amplified. The standard universal reverse primer L1 aligning to
      bacterial 23s rDNA was found unsuitable for some lactic acid bacteria and other
      species based on in silico analysis. Therefore, L1 primer was replaced by a
      combination of novel primers GplusR and GminusR aligning to the adjacent, more
      conserved DNA region. The amplification profiles were visualised by both standard
      electrophoresis and by fluorescent capillary gel electrophoresis. From
      representative samples, major amplicons were excised from the gel, cloned and
      sequenced. Sequencing revealed that the samples contained Lactobacillus
      delbrueckii, Lactobacillus brevis, Streptococcus thermophilus, Lactococcus
      lactis, Lactococcus raffinolactis, Streptococcus macedonicus, Leuconostoc
      pseudomesenteroides, Debaromyces hansenii, Mucor fragilis, Yarrowia lipolytica
      and Galactomyces geotrichum. These results represent an extension of the
      knowledge on the microflora of Slovakian bryndza cheese. The introduced automated
      ribosomal DNA intergenic spacer analysis of the bacterial and fungal genomes
      proved to be very effective in the application of studying microflora of cheese.

PMID- 21849218
TI  - Proteolytic activity of Saccharomyces cerevisiae strains associated with Italian
      dry-fermented sausages in a model system.
AB  - Strains of Saccharomyces cerevisiae isolated from Italian salami were screened
      for proteolytic activity in a model system containing sarcoplasmic (SMS) or
      myofibrillar (MMS) proteins, at 20 degrees C for 14days, to evaluate the possible
      influence on the proteolysis of fermented sausages. SDS-PAGE revealed that 14 of
      the most osmotolerant strains were responsible for the extensive hydrolysis of
      the main myofibrillar proteins, while only one strain was able to hydrolyze
      sarcoplasmic proteins. Free amino acids (FAA) accumulated during proteolysis were
      strain-dependent with different patterns from sarcoplasmic or myofibrillar
      protein fraction. In general, proteolysis lead Cys, Glu, Lys and Val as the most
      abundant FAA in the inoculated MMS samples. Volatile compound analysis,
      determined by SPME-GC-MS, evidenced 3-methyl butanol in MMS, and 2-methyl
      propanol and 3-methyl-1-butanol in SMS as major compounds. Our findings highlight
      that S. cerevisiae could influence the composition in amino acids and volatile
      compounds in fermented sausages, with a strain-dependent activity.

PMID- 21849219
TI  - Response surface methodology-based optimization of decontamination conditions for
      Escherichia coli O157:H7 and Salmonella Typhimurium on fresh-cut celery using
      thermoultrasound and calcium propionate.
AB  - A combination of thermoultrasound (temperature: 50, 55, 60 degrees C; time: 10,
      15, 20 min with the frequency of 40 KHz) and calcium propionate (concentration:
      1, 2, 3%, w/v) treatment was applied to decontaminate Escherichia coli O157:H7
      and Salmonella enterica serovar Typhimurium (S. Typhimurium) from fresh-cut
      celery. Using a Box-Behnken experimental design, predictive quadratic equations
      were developed for treatment-based population reductions of E. coli O157:H7
      (R(2)=0.98, p<0.001) and S. Typhimurium (R(2)=0.96, p<0.001), and verified using
      10 randomly selected treatment conditions. Among three factors (temperature,
      time, and calcium propionate concentration), temperature represented higher
      significance for inactivation of pathogenic bacteria. No significant changes
      (p>0.05) were observed in the color and shear force resistance of the treated
      celery. The optimum treatment conditions were 60 degrees C thermoultrasound with
      2% calcium propionate for 15 min (E. coli O157:H7) and 59 degrees C
      thermoultrasound with 2% calcium propionate for 17 min (S. Typhimurium). Scanning
      electron microscopy was used to confirm membrane disruption in the treated
      microbial cells in each optimal condition. The combined treatment of
      thermoultrasound and calcium propionate contributes to the effective inactivation
      (more than 5 log reduction) of E. coli O157:H7 and S. Typhimurium on fresh-cut
      celery. Furthermore, this treatment extends fresh storability without physical
      quality deterioration.

PMID- 21849220
TI  - CSI: a severity index for Clostridium difficile infection at the time of
      admission.
AB  - Clostridium difficile is a common cause of nosocomial diarrhoea in the USA. To
      develop a score model that would help to identify severe versus mild or moderate
      C. difficile infection (CDI) upon admission we performed a retrospective cohort
      study. Between January 2004 and December 2007, 255 patients met inclusion
      criteria for this study. Severe CDI was defined as cases that required colectomy,
      intensive care unit management, ended in death, or hospitalisation of >10 days.
      Data recorded included past medical history, physical examination on admission,
      laboratory data and imaging/colonoscopy data. To create the CDI severity index
      (CSI) score, we included four risk factors for severe CDI that were identified by
      univariate analysis: history of malignancy, white blood cell count at admission
      >20,000/dL, blood albumin <3.0mg/dL, and creatinine at admission >1.5-fold the
      baseline value. One point was assigned to each of the risk factors. As indicated
      by a c-statistic of 0.78, the CSI score predicted severe CDI much better than
      chance (c-statistics of 0.50). The risk of developing severe CDI increased by a
      factor of 2.9 (95% CI: 1.82-4.59) for each 1-point increase in the CSI score. A
      CSI score with a cut-off value of 2 had a sensitivity and specificity of 82% and
      65%, respectively. The CSI score may quantify the risk of severe CDI at the time
      of admission, and help in early identification of patients who may benefit from
      more aggressive treatment.

PMID- 21849221
TI  - Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as
      potential antimicrobial agents.
AB  - New series of 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 2
      substitued thio-6-phenyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles (5a-d, 6, 7a
      d, 8), 2-(4-chlorobenzylthio)-4-chloro-6-phenylpyrimidine-5-carbonitrile (9), 2
      (4-chlorobenzylthio)-4-arylthio-6-phenylpyrimidine-5-carbonitriles (10a-d) and 2
      (4-chlorobenzylthio)-4-arylamino-6-phenylpyrimidine-5-carbonitriles (11a-d) was
      synthesized and tested for in vitro activities against a panel of Gram-positive
      and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans.
      Compounds 5b, 5c, 6, 7a, 7b, 7c, 9 and 11a displayed marked antibacterial
      activity particularly against the tested Gram-positive bacteria, while compounds
      6, 7c, 7d and 9 were moderately or weakly active against C. albicans.

PMID- 21849222
TI  - Discovery and kinetic evaluation of 6-substituted 4-benzylthio-1,3,5-triazin
      2(1H)-ones as inhibitors of cathepsin B.
AB  - Cathepsin B is a lysosomal cysteine protease that has various physiological and
      pathophysiological functions. We present here the discovery of 6-substituted 4
      benzylthio-1,3,5-triazin-2(1H)-ones as inhibitors of cathepsin B, starting from
      screening of a library of variously 2,4,6-trisubstituted 1,3,5-triazines and
      1,3,5-triazin-2(1H)-ones on three different human cathepsins. The synthesis and
      enzymatic evaluation of a focused library of new 1,3,5-triazin-2(1H)-ones is also
      described. The detailed kinetics analyses have shown that these compounds can act
      as reversible, partial mixed-type inhibitors of cathepsin B, with K(i) and K(i)'
      values in the low micromolar range. The inhibitory activities of selected
      compounds were also assessed against two related cysteine proteases, cathepsin H
      and cathepsin L, to estimate their selectivity; these compounds have a selective
      profile for catB and catL over catH.

PMID- 21849223
TI  - "Finding my own time": examining the spatially produced experiences of rural RNs
      in the rural nursing certificate program.
AB  - CONTEXT: Rural nurses require access to education that exposes them to the most
      up-to-date information and skill development. However, since most education
      opportunities are located in urban centers and focused on providing skills to
      urban nurses, geography effectively acts as a barrier to accessing education that
      meets the needs of rural nurses. The Rural Nursing Certificate Program is a post
      basic education program that addresses these concerns by providing rural-relevant
      content online, with limited campus sessions. PURPOSE: Does online delivery of
      rural nursing curriculum overcome challenges related to geography? METHODS: This
      study employed surveys with some open-ended questions. Analysis included
      descriptive statistics and content analysis. FINDINGS: Students reported that
      online delivery improved access. Benefits included not having to relocate; being
      able to continue working; and, flexibility. Challenges included travel for
      practical experiences and time management related to staffing shortages, personal
      professional overlap and family responsibilities. CONCLUSIONS: Online learning
      improved access to nursing education. However, the realities of rural nursing
      made it impossible to completely overcome geography: sense of obligation to work
      overtime, cost and time of traveling to workshops and practicums, uneven access
      to the Internet and computer services, and distance from peer and university
      support remained challenges.

PMID- 21849224
TI  - Do facet screws provide the required stability in lumbar fixation? A
      biomechanical comparison of the Boucher technique and pedicular fixation in
      primary and circumferential fusions.
AB  - BACKGROUND: Transfacet pedicle screws are scarcely used in primary posterior
      fixation, and have limited use unilaterally or with existing anterior
      instrumentation. Nevertheless, the incomplete literature suggests equivalent or
      better performance of ipsilateral, bilateral, facet screws compared to bilateral
      pedicle screws. METHODS: Two groups of seven human cadaver spines (L3-S1) were
      tested under pure moments of 6 Nm. Each specimen was tested in a primary and
      circumferential fixation (Spacer, Spacer+Plate) environment. Both transfacet and
      bilateral pedicle screws were used as posterior fixation, in separate groups.
      Motion was obtained at L4-L5 for single-level constructs in flexion-extension,
      lateral bending and axial rotation modes. FINDINGS: In primary fixation, both
      transfacet and bilateral pedicle screws reduced motion below intact levels.
      Statistically, the level of circumferential fixation (anterior, posterior, or
      both) proved to be more influential than the type of posterior fixation.
      Incorporating a spacer and plate with pedicle screws provided a greater relative
      gain in stability than with facet screws. The interpretation is explained through
      a model describing the location of fixation with respect to the center-of
      rotation of the vertebral bodies. In lateral bending and axial rotation,
      bilateral pedicle screw constructs were stiffer than transfacet pedicle screw
      constructs as a trend. INTERPRETATION: Transfacet pedicle screws provided similar
      fixation to bilateral pedicle screws in primary and circumferential fixations
      during flexion-extension. In the other modes, transfacet screw rigidity is, on
      average, less than bilateral pedicle screws when used alone, but with the
      addition of other anterior instrumentation the differences are minimized.
      Therefore, facet screws are warranted based on the surgical effect desired, and
      in the presence of additional anterior fixation.

PMID- 21849225
TI  - Kidney tubular toxicity of maintenance pemetrexed therapy.
AB  - Pemetrexed is an antifolate agent approved for the treatment of advanced lung
      cancer. Major side effects include myelosuppression and neutropenia. Three
      patients developed kidney disease while being treated with maintenance
      pemetrexed. Kidney biopsy specimens showed tubulointerstitial injury with tubular
      simplification, shrinkage, loss of brush border, and tubular atrophy in a more
      advanced case. Kidney function remained impaired, but stable, after
      discontinuation of pemetrexed therapy in all cases.

PMID- 21849226
TI  - Pseudohypobicarbonatemia caused by an endogenous assay interferent: a new entity.
AB  - Serum total carbon dioxide, measured using a chemistry analyzer, and gas panel
      derived plasma bicarbonate, calculated from the pH and partial pressure of carbon
      dioxide, often are used interchangeably for clinical purposes. When they
      disagree, there is a tendency to accept total carbon dioxide and discredit gas
      panel-derived plasma bicarbonate values. We report a patient who, during a 5
      month hospitalization, had persistently low total carbon dioxide levels (12.4 +/-
      2.7 [standard deviation] mEq/L [12.4 +/- 2.7 mmol/L]), measured using an
      enzymatic/photometric assay, and a high anion gap (19.2 +/- 3.1 mEq/L [19.2 +/-
      3.1 mmol/L]), suggesting high-anion-gap metabolic acidosis, but who had gas panel
      derived plasma bicarbonate (24.0 +/- 0.9 mEq/L [24.0 +/- 0.9 mmol/L]) and
      arterial pH values in the reference range. Organic anion levels in blood and
      urine were unremarkable. Negative interference with the enzymatic assay by the
      patient's serum was shown by the findings that total carbon dioxide level was 7.0
      +/- 0.1 mEq/L (7.0 +/- 0.1 mmol/L) higher when measured using the electrode-based
      method than using the enzymatic method (P < 0.01), and the patient's serum, but
      not control serum, altered the reaction kinetics of the enzymatic assay by
      producing turbidity, resulting in an initial increase in absorbance and a falsely
      low total carbon dioxide value. The turbidity may have resulted from
      precipitation of 1 of 2 paraproteins in the patient's serum or an endogenous
      antibody binding with an animal protein included in the assay reagents. In
      summary, a discrepancy between total carbon dioxide level measured using an
      enzymatic assay and gas panel-derived plasma bicarbonate level was found to be
      the result of turbidity caused by an endogenous interferent with the total carbon
      dioxide assay, a novel artifact. When total carbon dioxide and gas panel-derived
      plasma bicarbonate values disagree, measurement error in total carbon dioxide
      level should be considered.

PMID- 21849228
TI  - Repeated peritoneal dialysis-associated peritonitis: a multicenter registry
      study.
AB  - BACKGROUND: Determinants and outcomes of peritoneal dialysis (PD)-associated
      peritonitis occurring within 4 weeks of completion of therapy of a prior episode
      caused by the same (relapse) or different organism (recurrence) recently have
      been characterized. However, determinants and outcomes of peritonitis occurring
      more than 4 weeks after treatment of a prior episode caused by the same
      (repeated) or different organism (nonrepeated) are poorly understood. STUDY
      DESIGN: Observational cohort study using Australia and New Zealand Dialysis and
      Transplant Registry (ANZDATA) data. SETTING & PARTICIPANTS: All Australian PD
      patients between October 1, 2003, and December 31, 2007, with first episodes of
      repeated or nonrepeated peritonitis. PREDICTORS: Repeated versus nonrepeated
      peritonitis, according to International Society of PD (ISPD) criteria. OUTCOMES &
      MEASUREMENTS: Relapse, hospitalization, catheter removal, hemodialysis transfer,
      and death. RESULTS: After a peritonitis episode, the probability that a
      subsequent episode represented repeated rather than nonrepeated peritonitis was
      highest in the second month (41%), then progressively decreased to a stable level
      of 14% from 6 months onward. When first episodes of repeated (n = 245) or
      nonrepeated peritonitis (n = 824) were analyzed, repeated peritonitis was
      predicted independently by a shorter elapsed time from the prior episode
      (adjusted OR per day elapsed, 0.91; 95% CI, 0.88-0.94). Staphylococcus aureus and
      coagulase-negative staphylococcus were isolated more frequently in repeated
      peritonitis, whereas Gram-negative, streptococcal, and fungal organisms were
      recovered more frequently in nonrepeated peritonitis. Using multivariate logistic
      regression, repeated peritonitis was associated independently with higher relapse
      (OR, 5.41; 95% CI, 3.72-7.89) and lower hospitalization rates (OR, 0.63; 95% CI,
      0.46-0.85), but catheter removal, hemodialysis transfer, and death rates similar
      to nonrepeated peritonitis. LIMITATIONS: Limited covariate adjustment. Residual
      confounding and coding bias could not be excluded. CONCLUSIONS: Repeated and
      nonrepeated peritonitis episodes are caused by different spectra of micro
      organisms and have different outcomes. Study findings suggest that the ISPD
      definition for repeated peritonitis should be limited to 6 months.

PMID- 21849227
TI  - Pathophysiology of metabolic alkalosis: a new classification based on the
      centrality of stimulated collecting duct ion transport.
AB  - Metabolic alkalosis is a unique acid-base disorder because it can be induced and
      sustained by functional alterations in renal ion transport. This review
      summarizes more than 50 years of research into the pathophysiologic processes
      causing this disorder. The evidence reviewed supports the hypothesis that
      virtually all forms of metabolic alkalosis are sustained by enhanced collecting
      duct hydrogen ion secretion, induced by stimulation of sodium uptake through the
      epithelial sodium channel (ENaC). Enhanced collecting duct hydrogen ion secretion
      in metabolic alkalosis occurs most commonly secondary to changes in ion transport
      earlier along the nephron, but also can occur as the result of primary
      stimulation of ENaC. In both these settings, potassium secretion is stimulated,
      and abnormal potassium losses cause depletion of body potassium stores. Potassium
      depletion has a key role in sustaining metabolic alkalosis by stimulating renal
      hydrogen ion secretion, enhancing renal ammonium production and excretion, and
      downregulating sodium reabsorption in the loop of Henle and early distal tubule.
      A new classification of the causes of metabolic alkalosis is proposed based on
      these pathophysiologic events rather than response to treatment.

PMID- 21849229
TI  - The interplay of structure and agency in health promotion: integrating a concept
      of structural change and the policy dimension into a multi-level model and
      applying it to health promotion principles and practice.
AB  - The recent debate in public health about the "inequality paradox" mirrors a long
      standing dispute between proponents of structuralist approaches and advocates of
      action theory. Both views are genuine perspectives of health promotion, but so
      far they have not been adequately linked by health promotion theory. Using
      Anthony Giddens's concepts of structure and agency seems promising, but his
      theory has a number of shortcomings that need to be amended if it is to be
      applied successfully to health promotion. After briefly assessing Giddens's
      theory of structuration, this paper proposes to add to it both the concept of
      structural change as proposed by William Sewell and the policy dimension as
      described by Elinor Ostrom in her distinction between "operational" and
      "collective choice" level. On this basis, a multi-level model of the interaction
      of structure and agency in health promotion is proposed. This model is then
      connected to central claims of the Ottawa Charter, i.e. "build healthy public
      policy", "create supportive environments", "strengthen community actions", and
      "develop personal skills". A case study from a local-level health promotion
      project in Germany is used to illustrate the explanatory power of the model,
      showing how interaction between structure and agency on the operational and on
      the collective choice level led to the establishment of women-only hours at the
      municipal indoor swimming pool as well as to increased physical activity levels
      and improved general self-efficacy among members of the target group.

PMID- 21849230
TI  - The role of smoking expectancies in the relationship between PTSD symptoms and
      smoking behavior among women exposed to intimate partner violence.
AB  - Intimate partner violence (IPV) is a public health problem associated with
      negative health consequences, including higher rates of tobacco smoking. Smoking
      expectancies are related to motivation to quit and relapse. IPV-exposed women
      endorse higher rates of PTSD symptoms, which are related to smoking and smoking
      expectancies. The present study sought to examine the relationship among smoking
      behavior, smoking expectancies, and PTSD symptoms among IPV-exposed women.
      Participants were 83 women who reported experiencing IPV within the last month,
      smoked an average of 12 cigarettes per day, and reported moderate levels of
      nicotine dependence (FTND mean=4.4). Participants completed baseline and follow
      up interviews. Multiple regression analyses assessed the relationships among
      smoking expectancies and PTSD symptoms to cigarettes smoked per day and nicotine
      dependence. Findings demonstrated that Stimulation/State Enhancement expectancies
      were positively related to cigarettes per day, whereas PTSD arousal symptoms were
      negatively related to cigarettes per day, p's<.05. Neither smoking expectancies
      nor PTSD symptoms were significantly related to nicotine dependence. Supplemental
      analyses revealed that PTSD re-experiencing symptoms were negatively related and
      PTSD avoidance/numbing symptoms were positively related to Stimulation/State
      Enhancement expectancies, p's<.05. This study extends findings regarding the
      association between PTSD symptoms and smoking among an understudied population -
      IPV-exposed women. The relationship between PTSD symptoms and smoking differed
      across PTSD symptom clusters and expectancy scales, which may have implications
      for treatment development. The fact that expectancies and PTSD symptoms are
      related to smoking behavior among IPV-exposed women may be important for
      enhancing prevention and intervention efforts.

PMID- 21849231
TI  - Occasional smoking in college: who, what, when and why?
AB  - INTRODUCTION: The majority of college students who smoke do so on an occasional
      basis and generally do not define themselves as smokers. This represents a
      considerable challenge for public health efforts to prevent escalation of use and
      to promote cessation. Strengthening such efforts will require further examination
      of the motivations behind occasional smoking within this vulnerable group.
      METHODS: Based within a priori identified content areas, we conducted eight focus
      groups of occasional smokers (N=53) at two demographically diverse colleges in
      the southeastern U.S. RESULTS: Few participants self-identified as a smoker and
      few had immediate desire to quit. Most identified extrinsic motivations for
      future quitting, including college graduation and parenthood. Although
      participants acknowledged smoking-related health risks, they minimized them as
      being personally irrelevant. Participants highlighted social (i.e., alcohol and
      other smokers) and stress-related smoking triggers. They also described how they
      carefully managed the situations in which they would, and would not smoke in
      order to preserve their identity. CONCLUSIONS: College students who smoke
      occasionally appear to engage in impression management, taking effort to shape
      their personal image to not appear as a smoker. They use smoking mainly as a
      social engagement tool, but also to alleviate negative emotions. They express
      minimal desire to quit and believe they are immune to the health risks of
      smoking. Public health messages should address this common pattern of smoking
      among young adults differently than regular smoking patterns by highlighting the
      social, emotional, and health consequences of occasional smoking before nicotine
      dependence has fully developed.

PMID- 21849233
TI  - The potential cost-effectiveness of general practitioner delivered brief
      intervention for alcohol misuse: evidence from rural Australia.
AB  - OBJECTIVE: This paper aims to model General Practitioner (GP) delivered screening
      and brief intervention (BI), and to identify the costs per additional risky
      drinker who reduces alcohol consumption to low-risk levels, relative to current
      practice. METHOD: A decision model and nine different scenarios were developed to
      assess outcomes and costs of GP-delivered screening and BI on the potential
      number of risky drinkers who reduce their alcohol consumption to low-risk levels
      in 10 rural communities in New South Wales, Australia. FINDINGS: Based on
      evidence from current practice, approximately 19% of all risky drinkers visiting
      GPs annually would reduce alcohol consumption to low-risk levels, of which 0.7%
      would do so because of GP-delivered screening and BI. If rates of screening and
      BI are increased to 100%, 36% of these risky drinkers would reduce their drinking
      to low risk-levels. Alternatively, increments of 10% and 20% in GP-delivered
      screening and BI would reduce the proportion of risky drinkers by 2.1% and 4.2%
      respectively. The most cost-effective outcome per additional risky drinker
      reducing their drinking relative to current practice would be if all of these
      risky drinkers are screened alone with an ICER of AUD$197. CONCLUSION: These
      findings indicate that increments in rates of screening and BI delivered by GPs
      can result in cost-effective reductions per additional risky drinkers reducing
      their drinking to low-risk levels, relative to current practice. They also imply
      that achieving substantial reductions in the prevalence of risky drinking in a
      community will require strategies other than opportunistic screening and BIs by
      GPs.

PMID- 21849232
TI  - The role of self-efficacy in the treatment of substance use disorders.
AB  - Self-efficacy is the belief that one has the ability to implement the behaviors
      needed to produce a desired effect. There has been growing interest in the role
      of self-efficacy as a predictor and/or mediator of treatment outcome in a number
      of domains. The present paper reviews the recent literature on self-efficacy in
      the substance abuse field. In numerous studies of substance abuse treatment, self
      efficacy has emerged as an important predictor of outcome, or as a mediator of
      treatment effects. Despite these repeated positive findings, the self-efficacy
      concept has had little impact on the design of treatments. Since the concept was
      first introduced, there have been numerous suggestions regarding the means by
      which self-efficacy may be enhanced in clinical settings, but very little by way
      of empirical tests of those suggestions. This review concludes with a number of
      recommendations for further research to improve understanding of this potentially
      valuable concept and its interactions with other variables, and to develop
      effective strategies for enhancing self-efficacy.

PMID- 21849234
TI  - Reward sensitivity and outcome expectancies as predictors of ecstasy use in young
      adults.
AB  - Extending recent studies showing that sensitivity to reward and outcome
      expectancies are associated with problematic alcohol and cannabis use, we
      undertook to determine if similar relationships would hold for ecstasy. One
      hundred and twenty five males and females aged between 18 and 35years were
      recruited from RMIT University and through snowball sampling. Participants
      completed a questionnaire package measuring frequency, amount and first age of
      ecstasy use, sensitivity to reward and punishment as well as outcome expectancies
      relating to ecstasy use. Frequency of ecstasy use was significantly related to
      reward sensitivity (p<.05) and positive outcome expectancies (p<.01). Regression
      analysis revealed significant prediction of ecstasy use by study variables, with
      expectations of increased confidence making the largest individual contribution.
      Multiple intervention points are suggested by the results of this study, within a
      largely cognitive-based framework.

PMID- 21849235
TI  - Relationship between muscle antioxidant status, forms of iron, polyunsaturated
      fatty acids and functionality (retail colour) of meat in lambs.
AB  - The relationship between muscle vitamin E, forms of iron, polyunsaturated fatty
      acids (PUFA) and the redness of meat (retail display) at days 3 to 4 post
      slaughter from lambs offered 2 different diets was examined. Meat redness was
      positively related to vitamin E and heme iron and negatively related to total n
      3, total n-6 and total PUFA content. However, after adjusting for the effects of
      vitamin E and heme iron content, there was no indication of any residual
      relationship between redness at days 3-4 of retail display and total n-3, total n
      6 or total PUFA. This indicates that the relationship between PUFA and redness in
      meat is mediated through the effects of heme iron and vitamin E in the muscle. It
      appears that the level of highly oxidisable PUFAs in muscle tissues do not play a
      major role in maintenance of redness at days 3-4 of retail display, but the level
      of vitamin E and heme iron content are important.

PMID- 21849236
TI  - Analysis of the complications of palmar plating versus external fixation for
      fractures of the distal radius.
AB  - PURPOSE: To evaluate whether there was a difference in complication rates in our
      patients treated with external fixation versus volar plating of distal radius
      fractures. We also looked for a difference in radiographic results; in the
      clinical outcomes of flexion, extension, supination, pronation, and grip
      strength; and in scores on the visual analog scale (VAS) for pain and the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. METHODS: We
      reviewed 115 patients with comminuted intrarticular distal radius fractures. Of
      those patients, 59 were treated with external fixation and 56 with volar plate
      fixation. Postoperative radiographs, range of motion, and grip strength were
      measured; DASH and VAS pain questionnaires were administered; and complications
      were documented. RESULTS: The external fixation group had a significantly higher
      overall complication rate. In the volar plate group, there were more tendon and
      median nerve complications, but this difference was not significant.
      Radiographically, the external fixator group demonstrated radial shortening of
      0.7 mm, whereas the volar plate group demonstrated 0.3 mm of radial shortening
      during the postoperative period. There were no significant differences between
      the groups in the measurement of scapholunate angle or palmar tilt. The mean DASH
      score at final follow-up was 32 in the external fixation group and 17 in the
      volar plate group, which was statistically significant. The final VAS scores were
      statistically different at 3.1 for the external fixation group and 1.1 for the
      volar plate group. On physical examination, the volar plate group had
      significantly better arc of motion in pronation-supination and flexion-extension
      and better grip strength. CONCLUSIONS: In the patients we studied, volar plate
      fixation has an overall decreased incidence of complications and significantly
      better motion in flexion-extension and supination-pronation compared to external
      fixation. Volar plate fixation also has less radial shortening than the external
      fixation group, yet the absolute difference in magnitude of ulnar variance was
      only 1.4 mm, calling into question the clinical significance of this difference.
      Patients with volar plating also have better pain and functional outcomes and
      better grip strength. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 21849237
TI  - A comparison of 2 methods for scaphoid central screw placement from a volar
      approach.
AB  - PURPOSE: We studied 2 methods used for screw placement through a volar approach
      for fixation of scaphoid fractures. METHODS: We performed measurements on 20
      computed tomography scans of unfractured scaphoids. A central virtual guidewire
      was computed in 10 scaphoids with the wrist in neutral or in extension and ulnar
      deviation. Second, we compared the central guidewire and a guidewire representing
      a volar approach to the scaphoid avoiding the trapezium. RESULTS: The central
      guidewire passed through the trapezium in all cases with the wrist either in
      neutral or in extension and ulnar deviation. There was a statistically
      significant difference only in the sagittal plane. When the central guidewire was
      compared with a guidewire placed through a standard volar approach, the latter
      was more eccentric in the distal and waist portions. CONCLUSIONS: We showed that
      central placement throughout the scaphoid with a standard volar approach is not
      feasible without partially resecting, manipulating, or drilling through the
      trapezium. CLINICAL RELEVANCE: Our data suggest that a volar transtrapezial
      approach can be an alternative for optimum central placement in volar
      percutaneous fixation of scaphoid fractures.

PMID- 21849238
TI  - Cubital tunnel syndrome caused by amyloid elbow arthropathy in long-term
      hemodialysis patients: report of 4 cases.
AB  - Carpal tunnel syndrome occurs frequently in long-term hemodialysis patients.
      However, the literature contains few detailed reports of other nerve entrapment
      syndromes of the upper extremity in these patients. We encountered 4 cases in
      which cubital tunnel syndrome occurred in long-term hemodialysis patients. In all
      cases, a hypertrophic synovial mass projecting from the humeroulnar joint
      compressed the ulnar nerve, and Congo red staining revealed that the mass
      contained amyloid deposition. Synovial proliferation resulting from amyloid
      arthropathy of the elbow joint appears to be the primary cause of this disease.

PMID- 21849239
TI  - The effects of ibuprofen on sepsis parameters in preterm neonates.
AB  - AIM: To examine the effects of ibuprofen used for patent ductus arteriosus (PDA)
      treatment on the production of the proinflammatory cytokines C-reactive protein
      (CRP) and interleukin 6 (IL-6) in preterm septic newborns. METHODS: Patients with
      acute phase reactant elevation were divided into two groups according to
      receiving ibuprofen (Group I, n=51) or not (Group II, n=38). Course of sepsis was
      evaluated by CRP and IL-6 levels. RESULTS: CRP and IL-6 levels at the time of
      diagnosis were not different between two groups [16+/-9.1 vs 16.4+/-13.2mg/dL
      (p=0.43) for CRP and 124+/-82 vs 119+/-73mg/dL (p=0.517) for IL-6, respectively].
      Similarly, they were statistically insignificant between the groups at the 2nd or
      3rd days of ibuprofen treatment [14.3+/-7.7 vs 13.7+/-5.9mg/dL (p=0.21) for CRP
      and 83+/-46 vs 86+/-37mg/dL (p=0.29) for IL-6, respectively]. However, CRP and
      IL6 levels showed significant difference between groups in the following days;
      6.03+/-3.8 vs 9.1+/-4.9mg/dL (p=0.025) for CRP and 42+/-33.1 vs 58.9+/-27.1mg/dL
      (0.011) for IL-6 on 4th or 5th days of treatment and 2.3+/-3.2 vs 4.1+/-2.3mg/dL
      (p=0.032) for CRP and 16.1+/-12.4 vs 21.3+/-16.8mg/dL (p=0.016) for IL-6, on 7th
      to 10th days of treatment, respectively. CONCLUSIONS: IL-6 and CRP may decrease
      in infants receiving ibuprofen treatment more than infants who do not receive it.
      This decrease should be considered at the time of caring a preterm infant with
      both sepsis and PDA after ibuprofen treatment.

PMID- 21849240
TI  - Executive function skills are associated with reading and parent-rated child
      function in children born prematurely.
AB  - BACKGROUND: Preterm children are at risk for executive function (EF) problems,
      which have been linked to behavior and learning problems in full term children.
      In this study, we examine the relationship between EF and functional outcomes in
      preterm children. AIM: To evaluate (1) EF skills of 9- to 16-year-old children
      born across the spectrum of gestational age (GA), (2) relationship of degree of
      prematurity to EF skills, and (3) contributions of EF skills to two functional
      outcomes - reading scores and parent-rated child function. METHOD: Preterm
      children <36 weeks gestation (n=72) were compared to full term children (n=42) of
      similar age, gender and SES, on measures of EF, reading, and parent-ratings of
      child function. Multiple regression models evaluated contributions to EF skills
      and functional outcomes. RESULTS: Compared to full term controls, preterm
      children had poorer EF performance on a complex planning and organization task
      and did not increase planning time as task difficulty increased. Their spatial
      memory capacity was not different. GA contributed to EF skills, but was mediated
      by IQ. EF contributed to the variance in reading skills but did not add to the
      variance in reading when IQ was considered. EF skills significantly contributed
      to the variance in parent-rated child function, but IQ did not. CONCLUSION: EF
      skills contribute to measures of functional outcome in this high-risk population.
      The use of EF skills as an early marker for learning and functional problems and
      as a target for intervention in children born preterm warrants future study.

PMID- 21849241
TI  - Power estimation predicts specific function action of acupuncture: an fMRI study.
AB  - PURPOSE: The purpose was to investigate the distinct pattern of brain response
      induced by electroacupuncture stimulation (EAS) related to sustained acupuncture
      effects. MATERIAL AND METHODS: Twenty-eight healthy volunteers were enrolled and
      randomized into two groups. According to grouping, volunteers were separately
      treated by EAS at GB37 (Guangming) or KI8 (Jiaoxin) during functional magnetic
      resonance imaging. Differences in acupuncture effects between the groups were
      tested by the power estimation approach. RESULTS: Spatial patterns of the whole
      brain power were different in the periaqueductal gray, occipital cortex (OC) and
      temporal cortex when induced by EAS at GB37 and KI8. Moreover, the differences in
      the sustained effects between these two acupoints were also identified and
      associated with the OC, dorsolateral prefrontal cortex, medial prefrontal cortex,
      anterior cingulate cortex and insula. CONCLUSION: Electroacupuncture stimulation
      induced different power fluctuation patterns related to GB37 and KI8. We suggest
      that these findings might be attributed to the specific function action of these
      acupoints.

PMID- 21849242
TI  - ACCF/AHA 2011 health policy statement on therapeutic interchange and
      substitution: a report of the American College of Cardiology Foundation Clinical
      Quality Committee.

PMID- 21849243
TI  - Prevention of seroma formation after axillary dissection in breast cancer: a
      systematic review.
AB  - BACKGROUND: The most common complication after breast cancer surgery is seroma
      formation. It is a source of significant morbidity and discomfort. Many articles
      have been published describing risk factors and preventive measures. The aim of
      this paper is to provide a systematic review of studies and reports on risk
      factors and preventive measures. Surgery lies at the core of seroma formation;
      therefore focus will be placed on surgical ways of reducing seroma. METHODS: A
      computer assisted medline search was carried out, followed by manual retrieval of
      relevant articles found in the reference listings of original articles. RESULTS:
      136 relevant articles were reviewed. Though the level of evidence remain varied
      several factors, type of dissection, tools with which dissection is carried out,
      reduction of dead space, suction drainage, use of fibrin glue and octreotide
      usage, have been found to correlate with seroma formation and have been shown to
      significantly reduce seroma rates. CONCLUSION: Seroma formation after breast
      cancer surgery cannot be avoided at present. There are however several methods to
      minimize seroma and associated morbidity. Future research should be directed
      towards the best ways of reducing seroma by combining proven methods.

PMID- 21849245
TI  - Reduced high and low frequency gamma synchronization in patients with chronic
      schizophrenia.
AB  - Schizophrenia has been conceptualized by dysfunctional cognition and behavior
      related to abnormalities in neural circuitry. The functioning of the neural
      circuitry can be assessed using the auditory steady state response (ASSR).
      Moreover, in recent years, research on high (>60 Hz) gamma band oscillations has
      become of increasing interest. The current study used whole-head, 306-channel
      magnetoencephalography (MEG) and investigated low and high gamma band
      oscillations with the ASSR. The subjects comprised 17 patients with schizophrenia
      and 22 controls. The current study investigated the MEG-ASSR elicited by click
      trains of 20-, 30-, 40- and 80-Hz frequencies, and symptom-ASSR associations in
      patients with schizophrenia. The mean power, phase-locking factor, dipole moments
      and source locations of the ASSR were estimated. The main findings were: (1)
      patients with schizophrenia showed bilaterally reduced ASSR power and dipole
      moments specific to the 40-Hz and 80-Hz frequencies; (2) patients with
      schizophrenia showed less right-greater-than-left 40-Hz ASSR power and phase
      locking factor compared with healthy subjects, indicating that schizophrenics may
      be characterized by an abnormal asymmetry of the 40-Hz ASSR; (3) increased
      severity of global hallucinatory experiences was significantly associated with
      smaller left 80-Hz MEG-ASSR in patients with schizophrenia. The current study
      highlights the high and low frequency gamma abnormalities and provides clear
      evidence that schizophrenia is characterized by abnormalities in neural
      circuitry.

PMID- 21849244
TI  - Prenatal cocaine exposure and small-for-gestational-age status: effects on growth
      at 6 years of age.
AB  - OBJECTIVE: To evaluate the impact of prenatal cocaine exposure and small-for
      gestational-age (SGA) status on childhood growth. STUDY DESIGN: Cocaine exposure
      was defined by history or meconium metabolites. Hierarchical linear modeling was
      used to examine cocaine exposure and SGA status on growth, while controlling for
      exposure to other drugs and alcohol use. RESULTS: At birth cocaine-exposed
      infants (n=364) had significantly lower growth parameters compared to non-exposed
      children (n=771). At 6 years, weight was similar between exposed and unexposed
      children. SGA infants continued to be growth impaired. There was a significant
      interaction between prenatal cocaine exposure and SGA status at 6 years. The
      negative effects of cocaine on weight and height were greater among non-SGA than
      SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative
      effects of SGA status on weight and height were larger in non-cocaine exposed
      compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).
      CONCLUSIONS: Children exposed to prenatal cocaine were similar in weight to non
      exposed children at 6 years of age. Cocaine had an unexplained greater
      detrimental effect on non-SGA than SGA children. SGA status at birth has an
      independent detrimental effect on childhood growth.

PMID- 21849246
TI  - Objective breast symmetry evaluation using 3-D surface imaging.
AB  - This study develops an objective breast symmetry evaluation using 3-D surface
      imaging (Konica-Minolta V910((r)) scanner) by superimposing the mirrored left
      breast over the right and objectively determining the mean 3-D contour difference
      between the 2 breast surfaces. 3 observers analyzed the evaluation protocol
      precision using 2 dummy models (n = 60), 10 test subjects (n = 300), clinically
      tested it on 30 patients (n = 900) and compared it to established 2-D
      measurements on 23 breast reconstructive patients using the BCCT.core software (n
      = 690). Mean 3-D evaluation precision, expressed as the coefficient of variation
      (VC), was 3.54 +/- 0.18 for all human subjects without significant intra- and
      inter-observer differences (p > 0.05). The 3-D breast symmetry evaluation is
      observer independent, significantly more precise (p < 0.001) than the BCCT.core
      software (VC = 6.92 +/- 0.88) and may play a part in an objective surgical
      outcome analysis after incorporation into clinical practice.

PMID- 21849248
TI  - Bisphosphonates that lack a nitrogen-containing side chain do not cause
      osteonecrosis of the jaws, regardless of their effect on STAT3 phosphorylation
      and SOCS3 expression.

PMID- 21849247
TI  - Conventional versus doxorubicin-eluting bead transarterial chemoembolization for
      hepatocellular carcinoma.
AB  - PURPOSE: To compare short- and long-term clinical outcomes after conventional
      transarterial chemoembolization and drug-eluting bead (DEB) transarterial
      chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      Patients with unresectable HCC unsuitable for ablative therapies were randomly
      assigned to undergo conventional or DEB chemoembolization. The primary endpoints
      of the study were safety, toxicity, and tumor response at 1 month. Secondary
      endpoints were number of repeated chemoembolization cycles, time to recurrence
      and local recurrence, time to radiologic progression, and survival. RESULTS: In
      total, 67 patients (mean age, 70 y +/- 7.7) were evaluated. Mean follow-up was
      816 days +/- 361. Two periprocedural major complications occurred (2.9%) that
      were treated by medical therapy without the need for other interventions. A
      significant increase in alanine aminotransferase levels 24 hours after treatment
      was reported, which was significantly greater after conventional
      chemoembolization (n = 34) than after DEB chemoembolization (n = 33;
      preprocedure, 60 IU +/- 44 vs 74 IU +/- 62, respectively; at 24 h, 216 IU +/- 201
      vs 101 IU +/- 89, respectively; P = 0.007). No other differences were observed in
      liver toxicity between groups. At 1 month, complete and partial tumor response
      rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization
      group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No
      differences were observed between groups in time to recurrence and local
      recurrence, radiologic progression, and survival. CONCLUSIONS: Conventional
      chemoembolization and DEB chemoembolization have a limited impact on liver
      function on short- and long-term follow-up and are associated with favorable
      clinical outcomes.

PMID- 21849251
TI  - A comparison of two gutta-percha obturation techniques to replicate canal
      irregularities in a split-tooth model.
AB  - OBJECTIVE: The purpose of this study was to compare a modified injectable gutta
      percha (MIGP) obturation technique with continuous wave technique (CWT) for the
      ability to fill the root canal system (RCS) and replicate artificially created
      intracanal defects at the apical third, using a split-tooth model. STUDY DESIGN:
      A maxillary canine was use to build a split-tooth model. The root canal was
      cleaned and shaped using crown-down technique with rotary files to size #40 at
      the apex. Intracanal defects were created in the dentin of the root canal walls
      with a half-round bur at the apical third. The canal was obturated 48 times with
      gutta-percha and sealer. Twenty-four obturations were performed for each
      technique, MIGP and CWT. After each obturation, the model was separated in 2
      halves; buccal and lingual. Each obturation was examined and photographed under
      operating microscope at *5 magnification. The images were blindly evaluated by 2
      endodontists for the length of gutta-percha fill, ability to fill the RCS,
      presence of voids, and replication of the canal defects. RESULTS: Results were
      analyzed with the Mann-Whitney U test and showed statistical difference between
      the 2 groups in the quality of the obturation (P < .05). CONCLUSIONS: The MIGP
      technique appeared to replicate the canal defects at the apical third better than
      CWT, with fewer voids in between the canal walls and the gutta-percha mass.

PMID- 21849252
TI  - Conscious sedation or general anaesthetic for intramuscular botulinum toxin
      injections in children - a two centre cross-sectional prospective audit.

PMID- 21849253
TI  - Microscopic thrombi in anaplastic astrocytoma predict worse survival?
AB  - The purpose of this study is to determine whether anaplastic astrocytoma patients
      with intratumoral vascular thrombi have a worse survival than anaplastic
      astrocytoma patients without thrombi. A retrospective review of 101 patients (60
      males; mean age, 53.3 years) with anaplastic astrocytoma (World Health
      Organization grade III) was conducted. Thrombi were counted relative to the
      number of involved blood vessels in the initially resected tumor (69 biopsies, 32
      subtotal resections) and were correlated with survival and development of
      postoperative deep venous thrombosis (DVT). Of tumors with thrombi (n = 17), the
      percentage of blood vessels with thrombi ranged from 1.5% to 20% (mean, 5.6%). Of
      these patients, 16 died of tumor (mean survival, 15.4 months), and 1 patient was
      alive with tumor at 180 months. Eighty-four patients with anaplastic astrocytoma
      had no intravascular tumor thrombi; 75 of these patients died of tumor (mean
      survival, 26.5 months), 4 patients were alive, and 5 patients were lost to follow
      up. Evidence of DVT was found in 2 (18.2%) of 11 tested patients with thrombi vs
      10 (18.5%) of 54 patients without thrombi. Patients with microscopic intratumoral
      thrombi (17% of anaplastic astrocytoma) had a worse survival compared with
      patients without thrombi; the difference did not reach statistical significance.
      There was no correlation between the presence of intratumoral thrombi and the
      development of DVT.

PMID- 21849255
TI  - Frequencies of different nuclear morphological features in prostate
      adenocarcinoma.
AB  - Diagnosis of prostate adenocarcinoma is primarily based on morphological
      analysis. Nucleomegaly, prominent nucleoli, and hyperchromasia constitute current
      nuclear diagnostic parameters but are seen in benign conditions, vary with
      Gleason grade, and pose diagnostic challenge in well-differentiated tumors with
      accompanying inflammation or equivocal architectural features. In such cases,
      other pleomorphic nuclear features such as variation in size and shape, irregular
      contours, nuclear membrane infoldings, and nonuniform chromatin, which are not
      incorporated in formal evaluation, may prove helpful. Our aim was to study
      different nuclear morphological features of prostate adenocarcinoma (including
      currently practiced ones) and highlight their variation with Gleason grades. We
      examined 84 cases of prostate adenocarcinoma using oil immersion microscopy where
      necessary. Commonest Gleason pattern observed was grade 4a accounting for 42.8%
      of cases. Nuclear enlargement (moderate to marked in 93.8%), nucleolar
      enlargement (62.1%), and nonuniform chromatin distribution (100%) could serve as
      useful diagnostic features but did not vary with tumor differentiation.
      Pleomorphism (moderate in 58.6%), nuclear overlapping (62.8%), nuclear membrane
      infoldings (66.2%), and irregular contours (frequent in 94.5%) were significant
      diagnostic features that increased in frequency and extent with increasing grade
      and could be used to differentiate low-grade from high-grade tumors. Worsening of
      nuclear morphology with advancing tumor grades indicated that nuclear anaplasia
      accompanies poor architectural differentiation. Coexistence of pale and dark
      nuclei signified variable chromatin density of no diagnostic significance.

PMID- 21849254
TI  - Crystal-storing histiocytosis: a rare lesion in periapical pathology.
AB  - Crystal-storing histiocytosis is a rare manifestation of plasma cell
      dyscrasia/monoclonal gammopathies and lymphoproliferative disorders,
      characterized by cytoplasmic accumulation of crystallized immunoglobulins in
      histiocytes. Nevertheless, some reported cases of crystal-storing histiocytosis
      raise the possibility that this lesion may also be reactive. Crystal-storing
      histiocytosis in the oral cavity is extremely rare; only one case affecting the
      tongue has been reported in the English-language literature. In this report, we
      discuss the case of a 38-year-old man who presented a persistent periapical
      lesion affecting the maxillary left lateral incisor. Histopathological analysis
      showed numerous crystal-laden histiocytes associated with a mild plasma cell
      infiltrate within a fibrous stroma. The plasma cells failed to show clonal light
      chain restriction, and the patient had no associated hematologic disorder or
      systemic disease. Thus, this lesion was probably the result of hypersecretion of
      immunoglobulins by polyclonal plasma cells found in the periapical lesion.
      Crystal-storing histiocytosis should be considered in the differential diagnosis
      of periapical lesions.

PMID- 21849256
TI  - Epithelioid schwannoma of soft tissue: unusual morphological variant causing a
      diagnostic dilemma.
AB  - Epithelioid variant of peripheral nerve sheath tumors is a rare but, at the same
      time, a well-known entity especially in the malignant counterpart. However,
      peculiar epithelioid morphology in soft tissue schwannomas is unusual and has
      been defined recently. These tumors may cause diagnostic errors owing to their
      increased cellularity and epithelioid morphology. Typical histologic features of
      classic schwannoma such as Antoni A and B areas, Verocay bodies, and hyalinized
      vessels are either absent or only present in focal areas. Furthermore, strong and
      diffuse S-100 protein expression is seen in both benign and malignant
      counterparts of epithelioid schwannoma. The findings that are suggestive of the
      benign nature of the lesion are long-term clinical history, small size,
      superficial localization, encapsulation, bland morphology, lack of mitosis and
      necrosis, and a benign clinical course after complete excision. Pathologists
      should be aware of the epithelioid variant of schwannoma to avoid false diagnosis
      of malignancy. We hereby report 3 cases of unusual benign epithelioid schwannoma
      of the soft tissue with special regard to problems in differential diagnosis.

PMID- 21849257
TI  - Immunohistochemical expression of ezrin in cutaneous basal and squamous cell
      carcinomas.
AB  - Ezrin is a member of the ezrin-radixin-moesin family of proteins, which link the
      actin-containing cytoskeleton to the plasma membrane. Overexpression of ezrin
      protein is correlated with the metastatic potential in several cancers. Little is
      known about the distribution of ezrin in normal epidermis and nonmelanoma skin
      cancer; therefore, in the current study, we examined the immunohistochemical
      expression of ezrin in normal skin (10 biopsies) and epithelial skin tumors (25
      basal cell carcinoma [BCC] and 20 squamous cell carcinoma [SCC]). Ezrin was
      expressed in epidermis of all normal controls with a prominent membranous pattern
      compared with 93.3% positivity in malignant cases with a significant higher
      intensity (assessed by H score) in favor of the latter (P = .002). Cytoplasmic
      expression of ezrin either alone or associated with membranous expression was
      both seen in BCC and SCC. The median value of H score in SCC (160) cases was
      higher than that in BCC (60). H score values of ezrin expression in BCC was
      significantly higher in tumors arising in sites other than the head and neck (P =
      .04). In SCC, the intensity of ezrin expression tended to be associated with
      advanced stage (P = .08). Our study demonstrated the probable tumorigenic role of
      ezrin in epithelial skin tumor formation. It may enhance local invasion or
      metastasis of epithelial skin tumors, which necessitates further larger study to
      clarify. The intensity rather than the pattern of ezrin expression had a more
      probable impact on the tumor behavior.

PMID- 21849258
TI  - A novel mutation in the coagulation factor 12 gene in subjects with hereditary
      angioedema and normal C1-inhibitor.
AB  - In hereditary angioedema with normal C1-inhibitor two different missense
      mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported
      in some families. In this study a novel factor 12 gene mutation, the deletion of
      72 base pairs (bp) (c.971_1018+24del72*), was identified in a family of Turkish
      origin, in two sisters with recurrent skin swellings and abdominal pain attacks
      and in their symptom-free father. This deletion caused a loss of 48 bp of exon 9
      (coding amino acids 324* to 340*) in addition to 24 bp of intron 9, including the
      authentic donor splice site of exon 9. The large deletion of 72 bp was located in
      the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg*
      reported previously. Our findings confirm the association between F12 gene
      mutations modifying the proline-rich region of the FXII protein and hereditary
      angioedema with normal C1-inhibitor.

PMID- 21849259
TI  - Anticonvulsant and depressant effects of aqueous extracts of Carum copticum seeds
      in male rats.
AB  - In this study, the effects of aqueous extracts of Carum copticum seeds (CCS) were
      evaluated in kindling models of epilepsy. Additionally, the sedative and
      anxiolytic effects of the extract were assessed. For pentylenetetrazole (PTZ)
      kindling, rats received a subconvulsant dose of PTZ (40 mg/kg, ip) every second
      day and seizure stages were recorded. CCS aqueous extract (200, 400, or 600
      mg/kg, ip) was injected 30 minutes prior to each PTZ injection. In electrical
      kindling, bipolar stimulating and monopolar recording electrodes were implanted
      stereotaxically in the right basolateral amygdala of male Sprague-Dawley rats.
      After kindling, the effect of aqueous extracts of CCS (200, 400, or 600 mg/kg,
      ip) on afterdischarge duration, duration of rearing, forelimb clonus, and loss of
      equilibrium (stage 5 seizure), and latency to the onset of bilateral forelimb
      clonus were measured. The sedative and the anxiolytic effects of CCS extracts
      were evaluated in an open-field apparatus and elevated plus maze, respectively.
      The results indicate that aqueous extracts of CCS have a significant
      anticonvulsant effect. Different doses of extract significantly delayed the
      incidence of every seizure stage in the PTZ model of kindling. Moreover, CCS
      extract (400 and 600 mg/kg, ip) suppressed afterdischarge duration, latency to
      the onset of bilateral forelimb clonus, and stage 5 seizure in the electrical
      kindling model. These results suggest that CCS extract has remarkable
      antiepileptic and central depressant effects.

PMID- 21849260
TI  - Cognitive effects of carisbamate in randomized, placebo-controlled, healthy
      volunteer, multidose studies.
AB  - Adverse cognitive effects are an important concern for drugs that influence the
      central nervous system. Carisbamate is a novel drug in development for treatment
      of seizures and neuropathic pain. Information on its cognitive effects is
      limited. Three controlled, multiple-dose, crossover studies with treatment
      durations of 5-9 days were designed to examine the cognitive effects of
      carisbamate on healthy volunteers. In one study, apparent dose-dependent effects
      on response, vigilance, and recognition speed were observed (1000 mg and 1500
      mg/day). Carisbamate did not differ from placebo for most variables in the other
      two studies, but increased reaction time and reduced Sternberg memory were seen
      at higher dosages. Carisbamate did not produce clinically significant adverse
      effects on cognitive performance at doses <1000 mg/day. Effects were mild to
      modest at the higher doses tested.

PMID- 21849261
TI  - Special education participation in children with epilepsy: what does it reflect?
AB  - Epilepsy is associated with academic and neurocognitive disorders, with the
      latter often assumed to explain the former. We examined utilization of special
      education services (SpES) in relation to neurocognitive test scores in a case
      matched sibling control study. In a follow-up assessment 8-9 years after entry
      into a prospective study of childhood-onset epilepsy, cases and siblings
      participated in an interview and standardized neurocognitive testing. Analyses
      included 142 pairs in which both had Full Scale IQ >= 80 and the case had normal
      examination and imaging. Sixty-four (45%) cases and 25 (17.6%) controls reported
      SpES utilization, (matched odds ratio [mOR]=5.3, P<0.0001). Adjustment for
      neurocognitive test scores resulted in a mOR of 4.6 (P<0.0001). Types and
      duration of services were similar in cases and controls. Twenty-four percent of
      school-aged cases were already receiving services at the time of initial epilepsy
      diagnosis. Young people with epilepsy have academic difficulties that are not
      explained simply by cognitive test scores.

PMID- 21849262
TI  - Management of gout in the older adult.
AB  - BACKGROUND: Gout affects 3 million people in the United States, with rates almost
      5 times higher in those aged 70 to 79 years compared with those aged < 50 years.
      Management of gout in elderly subjects can be complicated by comorbidities and
      polypharmacy. OBJECTIVE: The purpose of this article was to review the unique
      clinical presentation, treatment, and prevention of gout in the older adult, with
      attention to the age-related factors that may affect outcomes in this population.
      METHODS: PubMed and the Iowa Drug Information Service were searched (1944-January
      14, 2011) for clinical studies of gout using the following search terms: gout,
      elderly, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs),
      corticosteroid, prednisone, prednisolone, methylprednisolone, triamcinolone,
      allopurinol, febuxostat, probenecid, sulfinpyrazone, uricosuric, fenofibrate, and
      losartan. Articles were limited to clinical trials in humans, published in
      English. Citations of these articles were analyzed for additional relevant
      studies, and current guidelines were also consulted. RESULTS: Twenty-nine
      citations were reviewed. Evidence suggests that colchicine, NSAIDs, and
      corticosteroids are all efficacious in the treatment of acute gout in the older
      adult. Relevant limitations to colchicine use in the older adult include high
      cost, dosing restrictions in severe renal and hepatic dysfunction,
      gastrointestinal intolerance, and potential drug interactions. NSAID therapy is
      not recommended in older patients with congestive heart failure, renal failure,
      or gastrointestinal problems. Corticosteroids pose little risk when used in the
      short-term and may be preferred in patients with contraindications to colchicine
      or NSAIDs. Urate lowering with allopurinol for prevention of gout is well
      tolerated and has minimal cost per month; however, dose reduction is recommended
      in patients with renal impairment, which often results in failure to achieve
      target serum urate concentrations. Febuxostat does not require dose adjustment in
      mild to moderate renal disease and may be preferred in older people with this
      condition. CONCLUSION: Management of gout in the older adult involves careful
      selection of treatment based on potential benefits and consequences of therapy,
      considered in tandem with individual patient-specific characteristics.
      ClinicalTrials.gov identifiers NCT00549549, NCT01101035, NCT00241839,
      NCT01157936, NCT00997542, NCT00288158, and NCT00987415.

PMID- 21849263
TI  - Investigation of the mediated electron transfer mechanism of cellobiose
      dehydrogenase at cytochrome c-modified gold electrodes.
AB  - The present study reports on the comparison of direct and mediated electron
      transfer pathways in the interaction of the fungal enzyme cellobiose
      dehydrogenase (CDH) with the redox protein cytochrome c (cyt c) immobilised at a
      modified gold electrode surface. Two types of CDHs were chosen for this
      investigation: a basidiomycete (white rot) CDH from Trametes villosa and a
      recently discovered ascomycete from the thermophilic fungus Corynascus
      thermophilus. The choice was based on the pH-dependent interaction of these
      enzymes with cyt c in solution containing the substrate cellobiose (CB). Both
      enzymes show rather similar catalytic behaviour at lower pH, dominated by a
      direct electron exchange with the electrode. With increasing pH, however, also
      cyt c-mediated electron transfer becomes possible. The pH-dependent behaviour in
      the presence and in the absence of cyt c is analysed and the potential reaction
      mechanism for the two enzymes with a different pH-behaviour is discussed.

PMID- 21849264
TI  - Multicentre trial of weekly risedronate on bone density in adults with cystic
      fibrosis.
AB  - BACKGROUND: The aim of this study was to assess the efficacy, tolerability and
      safety of risedronate in adults with CF. METHODS: Patients with a lumbar spine
      (LS), total hip (TH) or femoral neck (FN) bone mineral density (BMD) Z-score of 
      1 or less were randomised to receive risedronate 35 mg weekly or placebo, and
      calcium (1g)+vitamin D(3) (800IU). RESULTS: At baseline, BMD Z-scores in the
      risedronate (n=17) and placebo (n=19) groups were similar. By 24 months, 7/17
      risedronate patients vs 0/19 placebo patients stopped the study medication due to
      bone pain. After 24 months treatment, the mean difference (95% CI) in change in
      LS, TH and FN BMD between the risedronate vs placebo groups was 4.3% (0.4, 8.2)
      p=0.03; 4.0% (-0.5, 8.6) p=0.08; and 2.4% (-3.5, 8.2) p=0.41. CONCLUSIONS: After
      two years treatment there was a significant increase in LS BMD with weekly
      risedronate compared to placebo.

PMID- 21849265
TI  - Chronic Stenotrophomonas maltophilia infection and exacerbation outcomes in
      cystic fibrosis.
AB  - BACKGROUND: Chronic Stenotrophomonas maltophilia infection is a risk factor for
      pulmonary exacerbation in cystic fibrosis (CF) but its impact on subsequent
      clinical outcomes is unknown. The aim of this study was to determine the effect
      of chronic S. maltophilia infection and associated antimicrobial therapy on the
      recovery of forced expiratory lung volume in 1s (FEV(1)) following pulmonary
      exacerbation. METHODS: This was a retrospective cohort study of patients with CF
      followed at The Hospital for Sick Children and St. Michael's Hospital from 1997
      to 2008. The primary outcome was the difference in FEV(1) percent predicted from
      baseline to follow up after a pulmonary exacerbation. Secondary outcomes for the
      effect of antimicrobial therapy included time to subsequent exacerbation.
      RESULTS: There were 1667 pulmonary exacerbations in 440 CF patients. Patients
      with chronic S. maltophilia infection did not recover their baseline FEV(1)
      following 31% of exacerbations and had an overall mean FEV(1) decline of 1.84%
      predicted after exacerbation. Older (p=0.02), female (p=0.02) patients with lower
      BMI z score (p=0.002) and Burkholderia cepacia complex infection (p=0.005), but
      not chronic S. maltophilia infection (p=0.86), had a greater decrease in follow
      up FEV(1)% pred compared to baseline. The number of days of antibiotic therapy
      against S. maltophilia during a pulmonary exacerbation was not associated with a
      significant difference in the FEV(1) recovery (p=0.69) or with a longer time to
      subsequent pulmonary exacerbation (p=0.56). CONCLUSIONS: Although CF patients
      experience a significant decline in lung function following exacerbation, chronic
      S. maltophilia infection and associated antimicrobial therapy do not affect
      subsequent lung function recovery.

PMID- 21849267
TI  - Differentially displayed genes with oxygen depletion stress and transcriptional
      responses in the marine mussel, Mytilus galloprovincialis.
AB  - Hypoxic events affecting aquatic environments have been reported worldwide and
      the hypoxia caused by eutrophication is considered one of the serious threats to
      coastal marine ecosystems. To investigate the molecular-level responses of marine
      organisms exposed to oxygen depletion stress and to explore the differentially
      expressed genes induced or repressed by hypoxia, differential display polymerase
      chain reaction (DD-PCR) was used with mRNAs from the marine mussel, Mytilus
      galloprovincialis, under oxygen depletion and normal oxygen conditions. In total,
      107 cDNA clones were differentially expressed under hypoxic conditions relative
      to the control mussel group. The differentially expressed genes were analyzed to
      determine the effects of hypoxia. They were classified into five functional
      categories: information storage and processing, cellular processes and signaling,
      metabolism, predicted general function only, and function unknown. The
      differentially expressed genes were predominantly associated with cellular
      processing and signaling, and they were particularly related to the signal
      transduction mechanism, posttranslational modification, and chaperone functions.
      The observed differences in the DD-PCR of 10 genes (encoding elongation factor 1
      alpha, heat shock protein 90, calcium/calmodulin-dependent protein kinase II,
      GTPase-activating protein, 18S ribosomal RNA, cytochrome oxidase subunit 1, ATP
      synthase, chitinase, phosphoglycerate/bisphosphoglycerate mutase family protein,
      and the nicotinic acetylcholine receptor) were confirmed by quantitative RT-PCR
      and their transcriptional changes in the mussels exposed to hypoxic conditions
      for 24-72 h were investigated. These results identify biomarker genes for hypoxic
      stress and provide molecular-level information about the effects of oxygen
      depletion on marine bivalves.

PMID- 21849266
TI  - Functional significance of the ATP-binding cassette transporter B6 in
      hepatocellular carcinoma.
AB  - ABCB6 is a mitochondrial transporter that regulates porphyrin biosynthesis. ABCB6
      expression is upregulated in hepatocellular carcinoma (HCC) but the significance
      of this upregulation to HCC is not known. In the present study, we investigated:
      1) ABCB6 expression in 18 resected human hepatocellular carcinoma (HCC) tissues
      and 3 human hepatoma cell lines; 2) pattern of ABCB6 expression during liver
      disease progression; and 3) functional significance of ABCB6 expression to HCC
      using the hepatoma cell line Huh7. ABCB6 expression was determined by real-time
      quantitative reverse transcription-polymerase chain reaction and western
      blotting. ABCB6 expression was upregulated in all the HCC specimens and the three
      hepatoma cell lines. Increased ABCB6 expression correlated with liver disease
      progression with the pattern of expression being HCC > cirrhosis > steatosis.
      Small hairpin RNA (shRNA)-mediated knockdown of ABCB6 in Huh7 cells lead to
      decreased cellular proliferation and colony formation. Attenuation of ABCB6
      expression did not affect Huh7 apoptosis but lead to a delay in G2/M phase of the
      cell cycle. In contrast, ABCB6 overexpression resulted in increased growth and
      proliferation of Huh7 cells. Since ABCB6 expression is induced in multiple tumor
      types we explored the role of ABCB6 in other cancer cells. ShRNA mediated
      knockdown of ABCB6 in HEK293 and K562 cells reduced cellular proliferation
      leading to a delay in G2/M phase, while ABCB6 overexpression promoted cell growth
      and proliferation. Collectively, these findings, obtained by loss of function and
      gain of function analysis, suggest that ABCB6 plays a role in cell growth and
      proliferation by targeting the cell cycle.

PMID- 21849268
TI  - Correction of flat auricular helix.

PMID- 21849269
TI  - Implantable cardioverter-defibrillator in a German shepherd dog with ventricular
      arrhythmias.
AB  - This report describes the use of an implantable cardioverter-defibrillator (ICD)
      in a young German shepherd dog afflicted with inherited ventricular arrhythmias.
      Proper generator and lead placement was necessary for successful termination of
      ventricular fibrillation during device testing at the time of implantation. The
      risks of inappropriate therapy triggered by sinus tachycardia and oversensing of
      the T wave were controlled by extensive programming of the device. Following
      spontaneous resolution of the arrhythmia and due to the development of sepsis
      associated with the device, the ICD was successfully removed.

PMID- 21849270
TI  - Aryl hydrocarbon receptor deficiency enhances insulin sensitivity and reduces
      PPAR-alpha pathway activity in mice.
AB  - BACKGROUND: Numerous man-made pollutants activate the aryl hydrocarbon receptor
      (AhR) and are risk factors for type 2 diabetes. AhR signaling also affects
      molecular clock genes to influence glucose metabolism. OBJECTIVE: We investigated
      mechanisms by which AhR activation affects glucose metabolism. METHODS: Glucose
      tolerance, insulin resistance, and expression of peroxisome proliferator
      activated receptor-alpha (PPAR-alpha) and genes affecting glucose metabolism or
      fatty acid oxidation and clock gene rhythms were investigated in wild-type (WT)
      and AhR-deficient [knockout (KO)] mice. AhR agonists and small interfering RNA
      (siRNA) were used to examine the effect of AhR on PPAR-alpha expression and
      glycolysis in the liver cell line Hepa-1c1c7 (c7) and its c12 and c4 derivatives.
      Brain, muscle ARNT-like protein 1 (Bmal1) siRNA and Ahr or Bmal1 expression
      plasmids were used to analyze the effect of BMAL1 on PPAR-alpha expression in c7
      cells. RESULTS: KO mice displayed enhanced insulin sensitivity and improved
      glucose tolerance, accompanied by decreased PPAR-alpha and key gluconeogenic and
      fatty acid oxidation enzymes. AhR agonists increased PPAR-alpha expression in c7
      cells. Both Ahr and Bmal1 siRNA reduced PPAR-alpha and metabolism genes.
      Moreover, rhythms of BMAL1 and blood glucose were altered in KO mice.
      CONCLUSIONS: These results indicate a link between AhR signaling, circadian
      rhythms, and glucose metabolism. Furthermore, hepatic activation of the PPAR
      alpha pathway provides a mechanism underlying AhR-mediated insulin resistance.

PMID- 21849271
TI  - Introduction to the 12th International Workshop on Multiple Endocrine Neoplasia.

PMID- 21849276
TI  - The history and mystery of VZV in saliva.

PMID- 21849277
TI  - Optimal treatment of Codisease due to HIV and tuberculosis.

PMID- 21849278
TI  - Persistence of varicella zoster virus DNA in saliva after herpes zoster.
AB  - Analysis of saliva samples from individuals aged >= 60 years who had a history of
      zoster (group 1), zoster and postherpetic neuralgia (PHN; group 2), or no history
      of zoster (group 3) revealed varicella zoster virus (VZV) DNA in saliva samples
      from 11 of 17 individuals in group 1, 10 of 15 individuals in group 2, and 2 of
      17 individuals in group 3. The frequency of VZV DNA detection was significantly
      higher (P = .001) in saliva of subjects with a history of zoster, with or without
      PHN (21 [67%] of 32 subjects in groups 1 and 2), than in saliva of age-matched
      subjects with no zoster history (2 [12%] of 17 subjects in group 3). Thus,
      persistence of VZV DNA in saliva is the outcome of zoster, independent of PHN.
      Because VZV infection can produce neurological and ocular disease without zoster
      rash, future studies are needed to establish whether VZV DNA can be detected in
      the saliva of such patients.

PMID- 21849279
TI  - Evaluation of three rapid screening assays for detection of antibodies to
      hepatitis C virus.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) estimates that
      3.2 million Americans are living with chronic hepatitis C virus (HCV) infection
      and 50%-70% are unaware of their status. Although therapies are available that
      can suppress or eliminate infection, identifying persons infected with HCV is
      challenging. Rapid tests could help identify many of these persons more
      expeditiously. METHODS: Three manufacturers, Chembio, OraSure, and MedMira,
      submitted HCV antibody (anti-HCV) rapid screening assays to the CDC for
      evaluation and comparison with established anti-HCV screening assays. The panel
      consisted of 1100 specimens drawn during 1997-1999 from persons reporting
      injection drug use. Sensitivity and specificity were assessed using 2 reference
      approaches, one based on the reactivity of samples in an anti-HCV screening assay
      and the other based on CDC HCV testing algorithm. RESULTS: The sensitivities of
      the Chembio, MedMira, and OraSure assays across the 2 approaches were 96.2%
      98.0%, 86.8%-88.3%, and 97.8%-99.3%, respectively. The 3 assays had specificity
      of 99.5% or higher with no differences between assays. False rapid assay results
      were associated with human immunodeficiency virus positivity for both approaches
      for Chembio and MedMira. CONCLUSIONS: Rapid anti-HCV tests can provide sensitive
      and specific anti-HCV results for high-risk patients.

PMID- 21849280
TI  - CXCL9 and CXCL10 chemokines as predictors of liver fibrosis in a cohort of
      primarily African-American injection drug users with chronic hepatitis C.
AB  - CXCL9 (monokine induced by IFN gamma [Mig]) and CXCL10 (interferon [IFN] gamma
      inducible protein 10 [IP-10]) have been associated with hepatic fibrosis in
      predominantly white hepatitis C virus (HCV)-infected patients. We investigated
      their potential as noninvasive markers of hepatic fibrosis and fibrosis
      progression in African-American patients. Peripheral chemokine levels were
      measured in 115 HCV-infected patients within 4 months of liver biopsy; patients
      underwent a second biopsy after 3-5 years. CXCL10 levels appeared to be higher in
      patients with advanced fibrosis on the contemporaneous biopsy and were
      significantly higher in patients with advanced fibrosis compared with those with
      minimal fibrosis on the later biopsy (P = .0045). Therefore, CXCL10 has potential
      as a marker of fibrosis progression in African-American HCV-infected patients.

PMID- 21849281
TI  - Clearance of genotype 1b hepatitis C virus in chimpanzees in the presence of
      vaccine-induced E1-neutralizing antibodies.
AB  - Accumulating evidence indicates that neutralizing antibodies play an important
      role in protection from chronic hepatitis C virus (HCV) infection. Efforts to
      elicit such responses by immunization with intact heterodimeric E1E2 envelope
      proteins have met with limited success. To determine whether antigenic sites,
      which are not exposed by the combined E1E2 heterodimer structure, are capable of
      eliciting neutralizing antibody responses, we expressed and purified each as
      separate recombinant proteins E1 and E2, from which the immunodominant
      hypervariable region (HVR-1) was deleted. Immunization of chimpanzees with either
      E1 or E2 alone induced antigen-specific T-helper cytokines of similar magnitude.
      Unexpectedly, the capacity to neutralize HCV was observed in E1 but not in
      animals immunized with E2 devoid of HVR-1. Furthermore, in vivo only E1
      vaccinated animals exposed to the heterologous HCV-1b inoculum cleared HCV
      infection.

PMID- 21849282
TI  - Immunogenicity of an inactivated monovalent 2009 H1N1 influenza vaccine in
      pregnant women.
AB  - BACKGROUND: Although pregnant women are at increased risk of severe illness
      following influenza infection, there is relatively little information on the
      immunogenicity of influenza vaccines administered during pregnancy. METHODS: We
      conducted a clinical trial that enrolled 120 pregnant women in which participants
      were randomly assigned to receive an inactivated 2009 H1N1 influenza vaccine
      containing either 25 MUg or 49 MUg of hemagglutinin (HA) in a 2-dose series with
      a 21-day period between administration of the first and second doses. RESULTS:
      Following the first vaccination, HA inhibition (HAI) titers of >=1:40 were
      detected in 93% (95% confidence interval [CI], 82%-98%) of subjects who received
      the 25-MUg dose and 97% (95% CI, 88%-100%) of subjects receiving the 49-MUg dose.
      In cord blood samples, HAI titers of >=1:40 were found in 87% (95% CI, 73%-96%)
      of samples from the 25-MUg dose group and in 89% (95% CI, 76%-96%) from the 49
      MUg dose group. Microneutralization titers tended to be higher than HAI titers,
      but the patterns of response were similar. CONCLUSIONS: In pregnant women, 1 dose
      of an inactivated 2009 H1N1 influenza vaccine containing 25 MUg of HA elicited an
      antibody response typically associated with protection against influenza
      infection. Efficient transplacental transfer of antibody was also documented.

PMID- 21849283
TI  - Altered pathogenicity for seasonal influenza virus by single reassortment of the
      RNP genes derived from the 2009 pandemic influenza virus.
AB  - BACKGROUND: The 2009 influenza A pandemic virus (H1N1(pdm)) may reassort with old
      seasonal influenza A virus (H1N1141) in humans and potentially change their
      pathogenicity. METHODS AND RESULTS: This study focuses on the reassortment of
      ribonucleoproteins (RNPs) among H1N1(pdm) and seasonal influenza A viruses. A
      single RNP gene reassortment altered reporter gene expression levels driven by
      polymerase complex in transfection system. The growth rates of recombinant
      viruses with different RNP recombinations were changed in A549 cells. Mice were
      infected with recombinant viruses containing single RNP gene reassortment, and
      pathogenicity was examined. The results demonstrated that the median lethal dose
      (LD50) of the PB2141/PB1141/PA(pdm)/NP141 recombinant virus was lower than that
      of the seasonal H1N1 virus. Viral titers of this reassorted virus in the lung and
      spleen were significantly higher than that in seasonal H1N1 virus-challenged
      mice. CONCLUSIONS: Although the changes of RNP activity did not exactly reflect
      to mice virulence, we consistently observed that the PA gene of H1N1(pdm) results
      in increased polymerase activity, better replication in mice, and lower LD50. Our
      findings suggest that monitoring of gene reassortment for the 2009 pandemic
      influenza and seasonal human viruses is also important, which would help to
      constrain the potential emergence of a more virulent influenza A variant.

PMID- 21849284
TI  - Cytokine signatures of innate and adaptive immunity in 17DD yellow fever
      vaccinated children and its association with the level of neutralizing antibody.
AB  - BACKGROUND: The live attenuated yellow fever (YF) vaccines have been available
      for decades and are considered highly effective and one of the safest vaccines
      worldwide. METHODS: The impact of YF-17DD-antigens recall on cytokine profiles of
      YF-17DD-vaccinated children were characterized using short-term cultures of whole
      blood samples and single-cell flow cytometry. This study enrolled seroconverters
      and nonseroconverters after primovaccination (PV-PRNT+ and PV-PRNT-),
      seroconverters after revaccination (RV-PRNT+), and unvaccinated volunteers (UV
      PRNT-). RESULTS: The analysis demonstrated in the PV-PRNT+ group a balanced
      involvement of pro-inflammatory/regulatory adaptive immunity with a prominent
      participation of innate immunity pro-inflammatory events (IL-12+ and TNF-alpha+
      NEU and MON). Using the PV-PRNT+ cytokine signature as a reference profile, PV
      PRNT- presented a striking lack of innate immunity proinflammatory response along
      with an increased adaptive regulatory profile (IL-4+CD4+ T cells and IL-10+ and
      IL-5+CD8+ T cells). Conversely, the RV-PRNT+ shifted the overall cytokine
      signatures toward an innate immunity pro-inflammatory profile and restored the
      adaptive regulatory response. CONCLUSIONS: The data demonstrated that the overall
      cytokine signature was associated with the levels of PRNT antibodies with a
      balanced innate/adaptive immunity with proinflammatory/regulatory profile as the
      hallmark of PV-PRNT(MEDIUM+), whereas a polarized regulatory response was
      observed in PV-PRNT- and a prominent proinflammatory signature was the
      characteristic of PV-PRNT(HIGH+).

PMID- 21849285
TI  - A randomized trial of punctuated antiretroviral therapy in Ugandan HIV
      seropositive adults with pulmonary tuberculosis and CD4+ T-cell counts of >= 350
      cells/MUL.
AB  - BACKGROUND: Optimal treatment of human immunodeficiency virus (HIV)-associated
      tuberculosis in patients with high CD4+ T-cell counts is unknown. Suppression of
      viral replication during therapy for tuberculosis may block effects of immune
      activation on T cells and slow HIV disease progression. METHODS: We conducted a
      randomized trial in 214 HIV-infected patients with active tuberculosis and CD4+ T
      cell counts of >= 350 cells/MUL to determine whether 6 months of antiretroviral
      therapy given during tuberculosis treatment would improve clinical outcomes.
      Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine
      concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints
      were CD4+ T-cell counts of < 250 cells/MUL, AIDS, or death. RESULTS: Intervention
      and comparison arms had similar median CD4+ counts (517 and 534 cells/MUL,
      respectively) and HIV RNA levels (4.6 and 4.7 log10 copies/MUL, respectively).
      Viral suppression was achieved in 86% of patients allocated to intervention.
      Seventeen subjects (15.6%) in the intervention arm developed study outcome
      compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4
      adverse events were less frequent in the intervention arm. By 2 months, 90% of
      subjects in both arms were culture-negative for tuberculosis. CONCLUSIONS: Short
      term antiretroviral therapy during tuberculosis treatment in patients with CD4+T
      cell counts of >350 cells/MUL was safe and associated with clinical benefits.

PMID- 21849287
TI  - Fine epitope specificity of anti-erythropoietin antibodies reveals molecular
      mimicry with HIV-1 p17 protein: a pathogenetic mechanism for HIV-1-related
      anemia.
AB  - BACKGROUND: Circulating autoantibodies to endogenous erythropoietin (anti-Epo)
      are detected in human immunodeficiency virus type 1 (HIV-1)-infected patients and
      represent a risk factor for anemia. The aim of this study was to map the B-cell
      epitopes on the Epo molecule. METHODS: Serum samples from HIV-1-positive patients
      and healthy individuals were tested against overlapping peptides covering the
      entire sequence of Epo. RESULTS: Serum samples from anti-Epo-positive patients
      exhibited significant binding to Epo epitopes spanning the following sequences:
      amino acids 1-20 (Ep1), amino acids 54-72 (Ep5), and amino acids 147-166 (Ep12).
      Structural analysis of erythropoietin revealed that the immunodominant epitopes,
      Ep1 and Ep12, comprise the interaction interface with Epo receptor (EpoR).
      Autoantibodies binding to this specific region are anticipated to inhibit the Epo
      EpoR interaction, resulting in blunted erythropoiesis; this phenomenon is
      indicated by the significantly higher Epo levels and lower hemoglobin levels of
      anti-Ep1-positive patients compared with anti-Ep1-negative individuals. The
      region corresponding to the Ep1 epitope exhibited a 63% sequence homology with
      the 34LVCASRELERFAVNPGLLE52 fragment of the HIV-1 p17 matrix protein.
      CONCLUSIONS: These results suggest that the main body of anti-Epo is directed
      against a functional domain of Epo, and that the presence of anti-Epo can be
      considered to be a result of a molecular mimicry mechanism, which is caused by
      the similarity between the Ep1 region and the p17 protein.

PMID- 21849288
TI  - Natural cholera infection-derived immunity in an endemic setting.
AB  - BACKGROUND: Live oral cholera vaccines may protect against cholera in a manner
      similar to natural cholera infections. However, information on which to base
      these vaccines is limited. METHODS: The study was conducted in a cholera-endemic
      population in Bangladesh. Patients with cholera (index patients) detected between
      1991 and 2000 were age-matched to 4 cholera-free controls and then followed up
      during the subsequent 3 years. RESULTS: El Tor cholera was associated with a 65%
      (95% confidence interval [CI], 37%-81%; P < .001) lower risk of a subsequent El
      Tor episode. Reduction of the risk of subsequent El Tor cholera was similar for
      children < 5 years and for older persons and was sustained during all 3 years of
      follow-up. Having El Tor Inaba cholera was associated with lower risks of both El
      Tor Inaba and El Tor Ogawa cholera, but having El Tor Ogawa cholera was
      associated only with a reduced risk of El Tor Ogawa cholera. O139 cholera was
      associated with a 63% (95% CI, -61% to 92%; P = .18) lower risk of subsequent
      O139 cholera, but there was no evidence of cross-protection between the O1 and
      O139 serogroups. CONCLUSIONS: Live oral cholera vaccines designed to protect
      against the O1 and O139 serogroups should contain at least the Inaba serotype and
      strains of both serogroups.

PMID- 21849289
TI  - Critical role for Streptococcus suis cell wall modifications and suilysin in
      resistance to complement-dependent killing by dendritic cells.
AB  - Streptococcus suis is an emerging zoonotic agent of septicemia and meningitis.
      Knowledge on host immune responses toward S. suis and strategies used by this
      pathogen for subversion of these responses is scarce. Here, S. suis modulation of
      dendritic cell (DC) functions were assessed for the first time. Using S. suis
      knockout mutants in capsular polysaccharide (CPS) expression, it was shown that
      CPS blocks DC phagocytosis and impairs cytokine release by hindering cell wall
      components. Mutants impaired in D-alanylation of lipoteichoic acid (LTA) or N
      deacetylation of peptidoglycan (PG) further demonstrated the importance of cell
      wall in modulation of DC activation. Notably, LTA/PG modifications were
      identified as major players in resistance to complement-dependent killing by DCs.
      Finally, S. suis hemolysin was partially involved in cytokine release and also
      contributed to bacterial escape of opsonophagocytosis. Overall, S. suis uses its
      arsenal of virulence factors to modulate DC functions and escape immune
      surveillance.

PMID- 21849286
TI  - Risk factors for tuberculosis after highly active antiretroviral therapy
      initiation in the United States and Canada: implications for tuberculosis
      screening.
AB  - BACKGROUND: Screening for tuberculosis prior to highly active antiretroviral
      therapy (HAART) initiation is not routinely performed in low-incidence settings.
      Identifying factors associated with developing tuberculosis after HAART
      initiation could focus screening efforts. METHODS: Sixteen cohorts in the United
      States and Canada contributed data on persons infected with human
      immunodeficiency virus (HIV) who initiated HAART December 1995-August 2009.
      Parametric survival models identified factors associated with tuberculosis
      occurrence. RESULTS: Of 37845 persons in the study, 145 were diagnosed with
      tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3
      months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence
      interval [CI]: 131-333 per 100000 person-years). In a multivariate Weibull
      proportional hazards model, baseline CD4+ lymphocyte count <200, black race,
      other nonwhite race, Hispanic ethnicity, and history of injection drug use were
      independently associated with tuberculosis risk. In addition, in a piece-wise
      Weibull model, increased baseline HIV-1 RNA was associated with increased
      tuberculosis risk in the first 3 months; male sex tended to be associated with
      increased risk. CONCLUSIONS: Screening for active tuberculosis prior to HAART
      initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm3
      or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history
      of injection drug use, and possibly male sex.

PMID- 21849290
TI  - Extracellular calcium reduction strongly increases the lytic capacity of
      pneumolysin from streptococcus pneumoniae in brain tissue.
AB  - BACKGROUND: Streptococcus pneumoniae causes serious diseases such as pneumonia
      and meningitis. Its major pathogenic factor is the cholesterol-dependent
      cytolysin pneumolysin, which produces lytic pores at high concentrations. At low
      concentrations, it has other effects, including induction of apoptosis. Many
      cellular effects of pneumolysin appear to be calcium dependent. METHODS: Live
      imaging of primary mouse astroglia exposed to sublytic amounts of pneumolysin at
      various concentrations of extracellular calcium was used to measure changes in
      cellular permeability (as judged by lactate dehydrogenase release and propidium
      iodide chromatin staining). Individual pore properties were analyzed by
      conductance across artificial lipid bilayer. Tissue toxicity was studied in
      continuously oxygenated acute brain slices. RESULTS: The reduction of
      extracellular calcium increased the lytic capacity of the toxin due to increased
      membrane binding. Reduction of calcium did not influence the conductance
      properties of individual toxin pores. In acute cortical brain slices, the
      reduction of extracellular calcium from 2 to 1 mM conferred lytic activity to
      pathophysiologically relevant nonlytic concentrations of pneumolysin.
      CONCLUSIONS: Reduction of extracellular calcium strongly enhanced the lytic
      capacity of pneumolysin due to increased membrane binding. Thus, extracellular
      calcium concentration should be considered as a factor of primary importance for
      the course of pneumococcal meningitis.

PMID- 21849291
TI  - Comparative analysis of USA300 virulence determinants in a rabbit model of skin
      and soft tissue infection.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      infections are frequently associated with strains harboring genes encoding Panton
      Valentine leukocidin (PVL). The role of PVL in the success of the epidemic CA
      MRSA strain USA300 remains unknown. Here we developed a skin and soft tissue
      infection model in rabbits to test the hypothesis that PVL contributes to USA300
      pathogenesis and compare it with well-established virulence determinants: alpha
      hemolysin (Hla), phenol-soluble modulin-alpha peptides (PSMalpha), and accessory
      gene regulator (Agr). The data indicate that Hla, PSMalpha, and Agr contribute to
      the pathogenesis of USA300 skin infections in rabbits, whereas a role for PVL
      could not be detected.

PMID- 21849292
TI  - Host cell lipid bodies triggered by Trypanosoma cruzi infection and enhanced by
      the uptake of apoptotic cells are associated with prostaglandin E2 generation and
      increased parasite growth.
AB  - Lipid bodies (lipid droplets) are lipid-rich organelles with functions in cell
      metabolism and signaling. Here, we investigate the mechanisms of Trypanosoma
      cruzi-induced lipid body formation and their contributions to host-parasite
      interplay. We demonstrate that T. cruzi-induced lipid body formation in
      macrophages occurs in a Toll-like receptor 2-dependent mechanism and is
      potentiated by apoptotic cell uptake. Lipid body biogenesis and prostaglandin E2
      (PGE2) production triggered by apoptotic cell uptake was largely dependent of
      alpha(v)beta3 and transforming growth factor-beta signaling. T. cruzi-induced
      lipid bodies act as sites of increased PGE synthesis. Inhibition of lipid body
      biogenesis by the fatty acid synthase inhibitor C75 reversed the effects of
      apoptotic cells on lipid body formation, eicosanoid synthesis, and parasite
      replication. Our findings indicate that lipid bodies are highly regulated
      organelles during T. cruzi infection with roles in lipid mediator generation by
      macrophages and are potentially involved in T. cruzi-triggered escape mechanisms.

PMID- 21849294
TI  - Deep sequencing of plasma and proviral HIV-1 to establish coreceptor usage: what
      is the clinical impact of the quasispecies distribution?

PMID- 21849293
TI  - The plasma concentration of the B cell activating factor is increased in children
      with acute malaria.
AB  - Malaria-specific antibody responses in children often appear to be short-lived
      but the mechanisms underlying this phenomenon are not well understood. In this
      study, we investigated the relationship between the B-cell activating factor
      (BAFF) and its receptors expressed on B cells with antibody responses during and
      after acute malaria in children. Our results demonstrate that BAFF plasma levels
      increased during acute malarial disease and reflected disease severity. The
      expression profiles for BAFF receptors on B cells agreed with rapid activation
      and differentiation of a proportion of B cells to plasma cells. However, BAFF
      receptor (BAFF-R) expression was reduced on all peripheral blood B cells during
      acute infection, but those children with the highest level of BAFF-R expression
      on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4
      months, indicating that dysregulation of BAFF-R expression on B cells may
      contribute to short-lived antibody responses to malarial antigens in children. In
      summary, this study suggests a potential role for BAFF during malaria disease,
      both as a marker for disease severity and in shaping the differentiation pattern
      of antigen-specific B cells.

PMID- 21849296
TI  - An unusual case of bilateral galactocoele in a male infant.

PMID- 21849297
TI  - Anti-Mullerian hormone--is it a crystal ball for predicting ovarian ageing?
AB  - Several studies have demonstrated that anti-Mullerian hormone (AMH) is a better
      marker of ovarian reserve than age, basal FSH, estradiol and inhibin. AMH is very
      good in (i) predicting both over- and poor-response in the controlled ovarian
      stimulation environment, (ii) determining the most appropriate stimulation
      regimen and (iii) pre-treatment counselling for couples to make an appropriate
      and informed choice. Recent reports are exploring the use of AMH in various other
      indications, including (i) predicting long-term fertility and guiding how long a
      woman can delay childbearing without facing the risk of reduced ovarian reserve,
      (ii) predicting the age of menopause, (iii) prediction of ovarian ageing in women
      prior to or following chemotherapy, (iv) prediction of long-term fertility
      following ovarian surgery and (v) screening for polycystic ovaries. However,
      widespread use of AMH for indications not proved by evidence-based medicine can
      lead to either false reassurance or distress, leading to unnecessary medical
      interventions . It also has huge implications for costs. We evaluated the
      evidence basis for using AMH for various indications to decide how justified it
      is to promote AMH as a crystal ball, until more evidence is available.

PMID- 21849298
TI  - Interaction between granulosa-lutein cells and monocytes regulates secretion of
      angiogenic factors in vitro.
AB  - BACKGROUND: Leukocyte infiltration and angiogenesis in the forming corpus luteum
      are prerequisites for normal ovarian function and may also underlie disorders
      like ovarian hyperstimulation syndrome. We examined whether ovarian angiogenesis
      could be affected by an interaction between granulosa-lutein (GL) cells and
      leukocytes. METHODS AND RESULTS: We found that GL cells isolated from the
      follicular fluid synthesize and secrete the chemokine interleukin-8 (IL-8), which
      activates IL-8-receptor-specific Ca(2+) and p38 mitogen-activated protein kinase
      signalling in monocytes and induces a directed migration of these cells towards
      the chemical gradient. Monocytes were found to further enhance IL-8 release,
      which suggests that these cells promote a massive leukocyte infiltration of the
      forming corpus luteum. A possible utility of leukocyte infiltration is the
      modulation of angiogenesis. We found that GL cells induce migration and capillary
      tube formation by endothelial cells in vitro. Furthermore, monocytes altered the
      profile of angiogenic factors released by GL cells, which supports the theory
      that an interaction between GL cells and leukocytes regulates ovarian
      angiogenesis. In addition, we found a correlation between increased secretion of
      pro-angiogenic cytokines and number of oocytes collected during IVF, which
      suggests that ovarian angiogenesis is related to the clinical response during
      ovarian stimulation. CONCLUSIONS: An intricate communication may exist between
      infiltrating leukocytes and ovarian GL cells during the formation of corpus
      luteum, affecting neo-vascularization of the luteal tissue.

PMID- 21849299
TI  - MicroRNAs are associated with human embryo implantation defects.
AB  - BACKGROUND: Repeated implantation failure (RIF) is a major problem encountered in
      IVF. We have previously reported that RIF-IVF patients have a different
      endometrial gene expression profile during the window of implantation.
      Considering microRNA (miRNA) function in post-transcriptional regulation of gene
      expression, the aim of the study was to evaluate the involvement of miRNA in
      defects of endometrial receptivity. METHODS: We used TaqMan miRNA array cards to
      identify the miRNAs differentially expressed in the secretory endometrium of RIF
      IVF patients when compared with fertile women, and bioinformatics tools to
      identify their predicted targets and the molecular networks they may affect.
      RESULTS: Comparing miRNA expression profiles, we identified 13 miRNAs,
      differentially expressed in RIF endometrial samples, that putatively regulate the
      expression of 3800 genes. We found that 10 miRNAs were overexpressed (including
      miR 145, 23b and 99a) and 3 were underexpressed. Using our previous gene
      expression analysis, we paralleled miRNA-mRNA expression profiling. By this
      means, we identified novel and previously characterized miRNA-regulated molecular
      pathways such as adherens junctions, cell adhesion molecules, Wnt-signaling, p53
      signaling and cell cycle pathways. Consistent with the miRNA-predicted targets,
      mRNA levels of N-cadherin, H2AFX, netrin-4 and secreted frizzled-related protein
      4, belonging to the cell adhesion molecules, Wnt signaling and cell cycle
      pathways were lower in RIF-IVF patients. CONCLUSIONS: To our knowledge, this is
      the first study to evaluate the differential expression of miRNAs in the
      secretory endometrium of RIF-IVF patients. We suggest that the RIF-associated
      miRNAs could be exploited as new candidates for diagnosis and treatment of embryo
      implantation failures.

PMID- 21849300
TI  - The post-reproductive Fallopian tube: better removed?
AB  - Recently, the distal Fallopian tube has attracted considerable attention not only
      as site of origin for serous cancer in women with BRCA mutations, but also as the
      anatomical location where the majority of serous ovarian cancers apparently
      develop. Consequently, the Fallopian tube may be the unique location where early
      'ovarian' cancers can be found--which would contradict the long-standing
      impression that the ovaries and the Fallopian tubes are always simultaneously
      involved. Based on the dismal prognosis associated with ovarian cancer and our
      inability to screen for early-stage disease, we discuss the rationale for
      introducing salpinges-hysterectomy as new clinical standard for women in need of
      hysterectomy and further weigh the arguments for and against bilateral
      salpingectomy as a sterilization method. There is no known physiological benefit
      of retaining the post-reproductive Fallopian tube during hysterectomy or
      sterilization, especially as this does not affect ovarian hormone production. On
      the other hand, the consequences associated with a surgical menopause provide a
      rationale for preserving the ovaries in premenopausal women. Prophylactic removal
      of the Fallopian tubes during hysterectomy or sterilization would rule out any
      subsequent tubal pathology, such as hydrosalpinx, which is observed in up to 30%
      of women after hysterectomy. Moreover, this intervention is likely to offer
      considerable protection against later tumour development, even if the ovaries are
      retained. Thus, we recommend that any hysterectomy should be combined with
      salpingectomy. In addition, women over 35 years of age could also be offered
      bilateral salpingectomy as means of sterilization.

PMID- 21849301
TI  - Difficult intrauterine device insertion.

PMID- 21849302
TI  - Gene expression profiling of peripheral blood mononuclear cells in endometriosis
      identifies genes altered in non-gynaecologic chronic inflammatory diseases.
AB  - BACKGROUND: Pelvic inflammatory phenomena have been suggested as critical players
      in the natural history of endometriosis. However, to what extent these events
      could affect the systemic immunologic status remains to be clarified. Here, we
      compared the gene expression profile in peripheral blood mononuclear cells from
      endometriosis patients in the severe diseased stage with the profile after a
      conventional surgical treatment for removal of endometriotic lesions and
      adhesions. METHODS: Microarray analysis included four patients suffering from
      severe endometriosis in which blood samples were obtained few days before the
      surgical intervention and again 6 months later. Real-time quantitative PCR
      analyses on a larger population were performed for some genes up-regulated in the
      diseased stage in a case-control approach. RESULTS: Among the 17,665 probe
      signals detected in the microarray, n = 26 genes resulted up-regulated and n = 15
      were down-regulated in the diseased stage. Five genes up-regulated in diseased
      stage (FBJ Murine osteosarcoma viral oncogene homolog gene, dual specificity
      phosphatase 1, pre-B-cell colony enhancing factor 1, adrenomedullin and S100
      calcium binding protein P) were exactly those shown as up-regulated in peripheral
      leukocytes of psoriasis patients in a very similar study design (diseased versus
      'cured' stage), with a 5.2 * 10(-11) hypergeometric probability that this event
      could occur by chance. CONCLUSIONS: Endometriosis induces the expression of genes
      in peripheral leukocytes already identified in non-gynaecologic chronic
      inflammatory diseases, thus revealing the disease as a local affliction with
      relevant consequences at the systemic level. Although the commonality of gene
      expression with other inflammatory diseases prevents the use of these genes as
      non-invasive diagnostic markers, from a clinical standpoint, the idea that the
      surgical intervention may reduce the expression of peripheral leukocyte genes
      represents a novel finding.

PMID- 21849303
TI  - Clinical analysis of anti-NR2 glutamate receptor antibodies and interleukin-6
      with neuropsychiatric systemic lupus erythematosus.

PMID- 21849304
TI  - Empirical antibiotics for suspected early neonatal sepsis.

PMID- 21849305
TI  - Effect of co-infusion of dextrose-containing solutions on red blood cell
      haemolysis during packed red cell transfusion.
AB  - AIM: Transfusion guidelines prohibit co-infusion of maintenance intravenous fluid
      solutions, with significant consequences for neonatal clinical care. This study
      investigated co-infusion-related haemolysis in an in vitro model closely
      resembling clinical practice. METHODS: Packed red blood cells (PRBCs, n=8) were
      co-infused at 5 and 10 ml/h with dextrose 5%, 10% and intravenous amino acid
      solution (synthamin). Free haemoglobin (fHb), as a measure of haemolysis, was
      measured by spectrophotometry and presented as % haemolysis and total fHb content
      (umol/l). RESULTS: Following co-infusion, there was no significant increase in
      PRBC haemolysis with either type of solution co-infused (p=0.82) or infusion rate
      (p=0.5). Neither macroscopic nor microscopic agglutination was observed during co
      infusion for any type of solution co-infused. CONCLUSIONS: Co-infusion does not
      result in increased haemolysis, with total fHb significantly lower than currently
      accepted safe thresholds for fHb. Adherence to current guidelines may place undue
      restrictions on current transfusion practice in neonatal intensive care.

PMID- 21849306
TI  - Archaeocete-like jaws in a baleen whale.
AB  - The titanic baleen whales (Cetacea, Mysticeti) have a bizarre skull morphology,
      including an elastic mandibular symphysis, which permits dynamic oral cavity
      expansion during bulk feeding. How this key innovation evolved from the sutured
      symphysis of archaeocetes has remained unclear. Now, mandibles of the Oligocene
      toothed mysticete Janjucetus hunderi show that basal mysticetes had an
      archaeocete-like sutured symphysis. This archaic morphology was paired with a
      wide rostrum typical of later-diverging baleen whales. This demonstrates that
      increased oral capacity via rostral widening preceded the evolution of mandibular
      innovations for filter feeding. Thus, the initial evolution of the mysticetes'
      unique cranial form and huge mouths was perhaps not linked to filtering plankton,
      but to enhancing suction feeding on individual prey.

PMID- 21849307
TI  - Elevated carbon dioxide affects behavioural lateralization in a coral reef fish.
AB  - Elevated carbon dioxide (CO(2)) has recently been shown to affect chemosensory
      and auditory behaviour, and activity levels of larval reef fishes, increasing
      their risk of predation. However, the mechanisms underlying these changes are
      unknown. Behavioural lateralization is an expression of brain functional
      asymmetries, and thus provides a unique test of the hypothesis that elevated
      CO(2) affects brain function in larval fishes. We tested the effect of near
      future CO(2) concentrations (880 uatm) on behavioural lateralization in the reef
      fish, Neopomacentrus azysron. Individuals exposed to current-day or elevated
      CO(2) were observed in a detour test where they made repeated decisions about
      turning left or right. No preference for right or left turns was observed at the
      population level. However, individual control fish turned either left or right
      with greater frequency than expected by chance. Exposure to elevated-CO(2)
      disrupted individual lateralization, with values that were not different from a
      random expectation. These results provide compelling evidence that elevated CO(2)
      directly affects brain function in larval fishes. Given that lateralization
      enhances performance in a number of cognitive tasks and anti-predator behaviours,
      it is possible that a loss of lateralization could increase the vulnerability of
      larval fishes to predation in a future high-CO(2) ocean.

PMID- 21849308
TI  - To fear or to feed: the effects of turbidity on perception of risk by a marine
      fish.
AB  - Coral reefs are currently experiencing a number of worsening anthropogenic
      stressors, with nearshore reefs suffering from increasing sedimentation because
      of growing human populations and development in coastal regions. In habitats
      where vision and olfaction serve as the primary sources of information, reduced
      visual input from suspended sediment may lead to significant alterations in prey
      fish behaviour. Here, we test whether prey compensate for reduced visual
      information by increasing their antipredator responses to chemically mediated
      risk cues in turbid conditions. Experiments with the spiny damselfish,
      Acanthochromis polyacanthus, found that baseline activity levels were reduced by
      23 per cent in high turbidity conditions relative to low turbidity conditions.
      Furthermore, risk cues elicited strong antipredator responses at all turbidity
      levels; the strongest antipredator responses were observed in high turbidity
      conditions, with fish reducing their foraging by almost 40 per cent, as compared
      with 17 per cent for fish in clear conditions. This provides unambiguous evidence
      of sensory compensation in a predation context for a tropical marine fish, and
      suggests that prey fish may be able to behaviourally offset some of the fitness
      reductions resulting from anthropogenic sedimentation of their habitats.

PMID- 21849310
TI  - Habitat tracking, stasis and survival in Neogene large mammals.
AB  - Species response to environmental change may vary from adaptation to the new
      conditions, to dispersal towards territories with better ecological settings
      (known as habitat tracking), and to extinction. A phylogenetically explicit
      analysis of habitat tracking in Caenozoic large mammals shows that species moving
      over longer distances during their existence survived longer. By partitioning the
      fossil record into equal time intervals, we showed that the longest distance was
      preferentially covered just before extinction. This supports the idea that
      habitat tracking is a key reaction to environmental change, and confirms that
      tracking causally prolongs species survival. Species covering longer distances
      also have morphologically less variable cheek teeth. Given the tight relationship
      between cheek teeth form and habitat selection in large mammals, this supports
      the well-known, yet little tested, idea that habitat tracking bolsters
      morphological stasis.

PMID- 21849309
TI  - Selection on codon usage and base composition in Drosophila americana.
AB  - We have used a polymorphism dataset on introns and coding sequences of X-linked
      loci in Drosophila americana to estimate the strength of selection on codon usage
      and/or biased gene conversion (BGC), taking into account a recent population
      expansion detected by a maximum-likelihood method. Drosophila americana was
      previously thought to have a stable demographic history, so that this evidence
      for a recent population expansion means that previous estimates of selection need
      revision. There was evidence for natural selection or BGC favouring GC over AT
      variants in introns, which is stronger for GC-rich than GC-poor introns. By
      comparing introns and coding sequences, we found evidence for selection on codon
      usage bias, which is much stronger than the forces acting on GC versus AT
      basepairs in introns.

PMID- 21849311
TI  - Bees do not use nearest-neighbour rules for optimization of multi-location
      routes.
AB  - Animals collecting patchily distributed resources are faced with complex multi
      location routing problems. Rather than comparing all possible routes, they often
      find reasonably short solutions by simply moving to the nearest unvisited
      resources when foraging. Here, we report the travel optimization performance of
      bumble-bees (Bombus terrestris) foraging in a flight cage containing six
      artificial flowers arranged such that movements between nearest-neighbour
      locations would lead to a long suboptimal route. After extensive training (80
      foraging bouts and at least 640 flower visits), bees reduced their flight
      distances and prioritized shortest possible routes, while almost never following
      nearest-neighbour solutions. We discuss possible strategies used during the
      establishment of stable multi-location routes (or traplines), and how these could
      allow bees and other animals to solve complex routing problems through
      experience, without necessarily requiring a sophisticated cognitive
      representation of space.

PMID- 21849312
TI  - Process factors affecting door to percutaneous coronary intervention for acute
      myocardial infarction patients.
AB  - The purpose of this cross-sectional study was to identify key predictor variables
      with the most impact on door-to-balloon time for acute myocardial infarction
      patients. The authors examined arrival, process, and patient-related variables
      from retrospective data from calendar years 2006 and 2007 within a single
      community hospital (N = 273). The door-to-balloon time ranged from 28 to 167
      minutes, with an average of 76.77 (standard deviation +/-24.5) minutes. Key
      predictor variables identified through multivariate linear regression included
      portable chest X-ray, presentation from walk-in versus ambulance, responding
      cardiology group, emergency department (ED) time of arrival (day 8 AM to 5 PM or
      night 5 PM to 8 AM), ED day of arrival (weekday or weekend), if a code R was
      called prior to arrival, and if the patient was identified as having chest pain
      on admission to the ED. For patients with acute myocardial infarction at a single
      study site, the authors identified a number of key factors that delay prompt
      reperfusion.

PMID- 21849313
TI  - A micro-geography of fear: learning to eavesdrop on alarm calls of neighbouring
      heterospecifics.
AB  - Many vertebrates eavesdrop on alarm calls of other species, which is a remarkable
      ability, given geographical variation in community composition and call diversity
      within and among species. We used micro-geographical variation in community
      composition to test whether individuals recognize heterospecific alarm calls by:
      (i) responding to acoustic features shared among alarm calls; (ii) having innate
      responses to particular heterospecific calls; or (iii) learning specific alarm
      calls. We found that superb fairy-wrens (Malurus cyaneus) fled to cover to
      playback of noisy miner (Manorina melanocephala) aerial predator alarm calls only
      in locations where miners were present, suggesting that learning rather than
      acoustic structure determines response. Sites with and without miners were well
      within the dispersal distance of fairy-wrens, and philopatric males and
      dispersing females showed the same pattern, so that local genetic adaptation is
      extremely unlikely. Furthermore, where miners were present, fairy-wrens responded
      appropriately to different miner calls, implying eavesdropping on their
      signalling system rather than fleeing from miners themselves. Learned
      eavesdropping on alarm calls enables individuals to harvest ecologically relevant
      information from heterospecifics on an astonishingly fine spatial scale. Such
      phenotypic plasticity is valuable in a changing world, where individuals can be
      exposed to new species.

PMID- 21849314
TI  - Parallel evolutionary trajectories underlie the origin of giant suspension
      feeding whales and bony fishes.
AB  - Giant suspension feeders such as mysticete whales, basking and whale sharks, and
      the extinct (indicated by '?') ?pachycormiform teleosts are conspicuous members
      of modern and fossil marine vertebrate faunas. Whether convergent anatomical
      features common to these clades arose along similar evolutionary pathways has
      remained unclear because of a lack of information surrounding the origins of all
      groups of large-bodied suspension feeders apart from baleen whales. New
      investigation reveals that the enigmatic ray-finned fish ?Ohmdenia, from the
      Lower Jurassic (Toarcian, 183.0-175.6 Ma) Posidonia Shale Lagerstatte, represents
      the immediate sister group of edentulous ?pachycormiforms, the longest lived
      radiation of large vertebrate suspension feeders. ?Ohmdenia bisects the long
      morphological branch leading to suspension-feeding ?pachycormiforms, providing
      information on the sequence of anatomical transformations preceding this major
      ecological shift that can be compared to changes associated with the origin of
      modern mysticetes. Similarities include initial modifications to jaw geometry
      associated with the reduction of dentition, followed by the loss of teeth. The
      evolution of largest body sizes within both radiations occurs only after the
      apparent onset of microphagy. Comparing the fit of contrasting evolutionary
      models to functionally relevant morphological measurements for whales and
      ?pachycormiform fishes reveals strong support for a common adaptive peak shared
      by suspension-feeding members of both clades.

PMID- 21849315
TI  - Vector host-feeding preferences drive transmission of multi-host pathogens: West
      Nile virus as a model system.
AB  - Seasonal epizootics of vector-borne pathogens infecting multiple species are
      ecologically complex and difficult to forecast. Pathogen transmission potential
      within the host community is determined by the relative abilities of host species
      to maintain and transmit the pathogen and by ecological factors influencing
      contact rates between hosts and vectors. Increasing evidence of strong feeding
      preferences by a number of vectors suggests that the host community experienced
      by the pathogen may be very different from the local host community. We developed
      an empirically informed transmission model for West Nile virus (WNV) in four
      sites using one vector species (Culex pipiens) and preferred and non-preferred
      avian hosts. We measured strong feeding preferences for American robins (Turdus
      migratorius) by Cx. pipiens, quantified as the proportion of Cx. pipiens blood
      meals from robins in relation to their abundance (feeding index). The model
      accurately predicted WNV prevalence in Cx. pipiens at three of four sites.
      Sensitivity analysis revealed feeding preference was the most influential
      parameter on intensity and timing of peak WNV infection in Cx. pipiens and a
      threshold feeding index for transmission was identified. Our findings indicate
      host preference-induced contact heterogeneity is a key mediator of vector-borne
      pathogen epizootics in multi-species host communities, and should be incorporated
      into multi-host transmission models.

PMID- 21849316
TI  - Nonlinear time-series approaches in characterizing mood stability and mood
      instability in bipolar disorder.
AB  - Bipolar disorder is a psychiatric condition characterized by episodes of elevated
      mood interspersed with episodes of depression. While treatment developments and
      understanding the disruptive nature of this illness have focused on these
      episodes, it is also evident that some patients may have chronic week-to-week
      mood instability. This is also a major morbidity. The longitudinal pattern of
      this mood instability is poorly understood as it has, until recently, been
      difficult to quantify. We propose that understanding this mood variability is
      critical for the development of cognitive neuroscience-based treatments. In this
      study, we develop a time-series approach to capture mood variability in two
      groups of patients with bipolar disorder who appear on the basis of clinical
      judgement to show relatively stable or unstable illness courses. Using weekly
      mood scores based on a self-rated scale (quick inventory of depressive
      symptomatology-self-rated; QIDS-SR) from 23 patients over a 220-week period, we
      show that the observed mood variability is nonlinear and that the stable and
      unstable patient groups are described by different nonlinear time-series
      processes. We emphasize the necessity in combining both appropriate measures of
      the underlying deterministic processes (the QIDS-SR score) and noise
      (uncharacterized temporal variation) in understanding dynamical patterns of mood
      variability associated with bipolar disorder.

PMID- 21849317
TI  - Understanding sex differences in the cost of terrestrial locomotion.
AB  - Little is known regarding the physiological consequences of the behavioural and
      morphological differences that result from sexual selection in birds. Male and
      female Svalbard rock ptarmigans (Lagopus muta hyperborea) exhibit distinctive
      behavioural differences during the breeding season. In particular, males
      continuously compete for and defend territories in order to breed successfully,
      placing large demands on their locomotor system. Here, we demonstrate that male
      birds have improved locomotor performance compared with females, showing both a
      lower cost of locomotion (CoL) and a higher top speed. We propose that the
      observed sex differences in locomotor capability may be due to sexual selection
      for improved male performance. While the mechanisms underlying these energetic
      differences are unclear, future studies should be wary when pooling male and
      female data.

PMID- 21849318
TI  - Multi-objective optimization shapes ecological variation.
AB  - Ecological systems contain a huge amount of quantitative variation between and
      within species and locations, which makes it difficult to obtain unambiguous
      verification of theoretical predictions. Ordinary experiments consider just a few
      explanatory factors and are prone to providing oversimplified answers because
      they ignore the complexity of the factors that underlie variation. We used multi
      objective optimization (MO) for a mechanistic analysis of the potential
      ecological and evolutionary causes and consequences of variation in the life
      history traits of a species of moth. Optimal life-history solutions were sought
      for environmental conditions where different life stages of the moth were subject
      to predation and other known fitness-reducing factors in a manner that was
      dependent on the duration of these life stages and on variable mortality rates.
      We found that multi-objective optimal solutions to these conditions that the
      moths regularly experience explained most of the life-history variation within
      this species. Our results demonstrate that variation can have a causal
      interpretation even for organisms under steady conditions. The results suggest
      that weather and species interactions can act as underlying causes of variation,
      and MO acts as a corresponding adaptive mechanism that maintains variation in the
      traits of organisms.

PMID- 21849319
TI  - Repeated modification of early limb morphogenesis programmes underlies the
      convergence of relative limb length in Anolis lizards.
AB  - The independent evolution of similar morphologies has long been a subject of
      considerable interest to biologists. Does phenotypic convergence reflect the
      primacy of natural selection, or does development set the course of evolution by
      channelling variation in certain directions? Here, we examine the ontogenetic
      origins of relative limb length variation among Anolis lizard habitat specialists
      to address whether convergent phenotypes have arisen through convergent
      developmental trajectories. Despite the numerous developmental processes that
      could potentially contribute to variation in adult limb length, our analyses
      reveal that, in Anolis lizards, such variation is repeatedly the result of
      changes occurring very early in development, prior to formation of the
      cartilaginous long bone anlagen.

PMID- 21849320
TI  - For better or worse: reduced adult lifespan following early-life stress is
      transmitted to breeding partners.
AB  - Stressful conditions early in life can give rise to exaggerated stress responses,
      which, while beneficial in the short term, chronically increase lifetime exposure
      to stress hormones and elevate disease risk later in life. Using zebra finches
      Taeniopygia guttata, we show here that individuals whose glucocorticoid stress
      hormones were experimentally increased for only a brief period in early post
      natal life, inducing increased stress sensitivity, had reduced adult lifespans.
      Remarkably, the breeding partners of such exposed individuals also died at a
      younger age. This negative effect on partner longevity was the same for both
      sexes; it occurred irrespective of the partner's own early stress exposure and
      was in addition to any longevity reduction arising from this. Furthermore, this
      partner effect continued even after the breeding partnership was terminated. Only
      5 per cent of control birds with control partners had died after 3 years,
      compared with over 40 per cent in early stress-early stress pairs. In contrast,
      reproductive capability appeared unaffected by the early stress treatment, even
      when breeding in stressful environmental circumstances. Our results clearly show
      that increased exposure to glucocorticoids early in life can markedly reduce
      adult life expectancy, and that pairing with such exposed partners carries an
      additional and substantial lifespan penalty.

PMID- 21849321
TI  - A 'living fossil' eel (Anguilliformes: Protanguillidae, fam. nov.) from an
      undersea cave in Palau.
AB  - We report the discovery of an enigmatic, small eel-like fish from a 35 m-deep
      fringing-reef cave in the western Pacific Ocean Republic of Palau that exhibits
      an unusual suite of morphological characters. Many of these uniquely characterize
      the Recent members of the 19 families comprising the elopomorph order
      Anguilliformes, the true eels. Others are found among anguilliforms only in the
      Cretaceous fossils, and still others are primitive with respect to both Recent
      and fossil eels. Thus, morphological evidence explicitly places it as the most
      basal lineage (i.e. the sister group of extant anguilliforms). Phylogenetic
      analysis and divergence time estimation based on whole mitogenome sequences from
      various actinopterygians, including representatives of all eel families,
      demonstrate that this fish represents one of the most basal, independent lineages
      of the true eels, with a long evolutionary history comparable to that of the
      entire Anguilliformes (approx. 200 Myr). Such a long, independent evolutionary
      history dating back to the early Mesozoic and a retention of primitive
      morphological features (e.g. the presence of a premaxilla, metapterygoid, free
      symplectic, gill rakers, pseudobranch and distinct caudal fin rays) warrant
      recognition of this species as a 'living fossil' of the true eels, herein
      described as Protanguilla palau genus et species nov. in the new family
      Protanguillidae.

PMID- 21849322
TI  - Oviposition strategy as a means of local adaptation to plant defence in native
      and invasive populations of the viburnum leaf beetle.
AB  - Herbivores have been hypothesized to adapt locally to variation in plant defences
      and such adaptation could facilitate novel associations in the context of
      biological invasions. Here, we show that in the native range of the viburnum leaf
      beetle (VLB, Pyrrhalta viburni), two populations of geographically isolated hosts
      Viburnum opulus and Viburnum tinus-have divergent defences against VLB
      oviposition: negative versus positive density-dependent egg-crushing wound
      responses, respectively. Populations of beetles coexisting with each host show an
      adaptive behavioural response: aggregative versus non-aggregative oviposition on
      V. opulus and V. tinus, respectively. In parallel, we show that in North America,
      where VLB is invasive, defences of three novel hosts are negatively density
      dependent, and beetles' oviposition behaviour is aggregative. Thus, local
      adaptation to plant defences has the potential to facilitate the invasion of
      herbivores onto novel hosts.

PMID- 21849323
TI  - Shoot, shovel and shut up: cryptic poaching slows restoration of a large
      carnivore in Europe.
AB  - Poaching is a widespread and well-appreciated problem for the conservation of
      many threatened species. Because poaching is illegal, there is strong incentive
      for poachers to conceal their activities, and consequently, little data on the
      effects of poaching on population dynamics are available. Quantifying poaching
      mortality should be a required knowledge when developing conservation plans for
      endangered species but is hampered by methodological challenges. We show that
      rigorous estimates of the effects of poaching relative to other sources of
      mortality can be obtained with a hierarchical state-space model combined with
      multiple sources of data. Using the Scandinavian wolf (Canis lupus) population as
      an illustrative example, we show that poaching accounted for approximately half
      of total mortality and more than two-thirds of total poaching remained undetected
      by conventional methods, a source of mortality we term as 'cryptic poaching'. Our
      simulations suggest that without poaching during the past decade, the population
      would have been almost four times as large in 2009. Such a severe impact of
      poaching on population recovery may be widespread among large carnivores. We
      believe that conservation strategies for large carnivores considering only
      observed data may not be adequate and should be revised by including and
      quantifying cryptic poaching.

PMID- 21849324
TI  - Impact of aragonite saturation state changes on migratory pteropods.
AB  - Thecosome pteropods play a key role in the food web of various marine ecosystems
      and they calcify, secreting the unstable CaCO(3) mineral aragonite to form their
      shell material. Here, we have estimated the effect of ocean acidification on
      pteropod calcification by exploiting empirical relationships between their gross
      calcification rates (CaCO(3) precipitation) and aragonite saturation state
      Omega(a), combined with model projections of future Omega(a). These were
      corrected for modern model-data bias and taken over the depth range where
      pteropods are observed to migrate vertically. Results indicate large reductions
      in gross calcification at temperate and high latitudes. Over much of the Arctic,
      the pteropod Limacina helicina will become unable to precipitate CaCO(3) by the
      end of the century under the IPCC SRES A2 scenario. These results emphasize
      concerns over the future of shelled pteropods, particularly L. helicina in high
      latitudes. Shell-less L. helicina are not known to have ever existed nor would we
      expect them to survive. Declines of pteropod populations could drive dramatic
      ecological changes in the various pelagic ecosystems in which they play a
      critical role.

PMID- 21849325
TI  - Zinc-finger recombinase activities in vitro.
AB  - Zinc-finger recombinases (ZFRs) are chimaeric proteins comprising a serine
      recombinase catalytic domain linked to a zinc-finger DNA binding domain. ZFRs can
      be tailored to promote site-specific recombination at diverse 'Z-sites', which
      each comprise a central core sequence flanked by zinc-finger domain-binding
      motifs. Here, we show that purified ZFRs catalyse efficient high-specificity
      reciprocal recombination between pairs of Z-sites in vitro. No off-site activity
      was detected. Under different reaction conditions, ZFRs can catalyse Z-site
      specific double-strand DNA cleavage. ZFR recombination activity in Escherichia
      coli and in vitro is highly dependent on the length of the Z-site core sequence.
      We show that this length effect is manifested at reaction steps prior to
      formation of recombinants (binding, synapsis and DNA cleavage). The design of the
      ZFR protein itself is also a crucial variable affecting activity. A ZFR with a
      very short (2 amino acids) peptide linkage between the catalytic and zinc-finger
      domains has high activity in vitro, whereas a ZFR with a very long linker was
      less recombination-proficient and less sensitive to variations in Z-site length.
      We discuss the causes of these phenomena, and their implications for practical
      applications of ZFRs.

PMID- 21849326
TI  - Expression level drives the pattern of selective constraints along the
      insulin/Tor signal transduction pathway in Caenorhabditis.
AB  - Genes do not act in isolation but perform their biological functions within
      genetic pathways that are connected in larger networks. Investigation of
      nucleotide variation within genetic pathways and networks has shown that topology
      can affect the rate of protein evolution; however, it remains unclear whether a
      same pattern of nucleotide variation is expected within functionally similar
      networks and whether it may be due to similar or different biological mechanisms.
      We address these questions by investigating nucleotide variation in the context
      of the structure of the insulin/Tor-signaling pathway in Caenorhabditis, which is
      well characterized and is functionally conserved across phylogeny. In Drosophila
      and vertebrates, the rate of protein evolution is negatively correlated with the
      position of a gene within the insulin/Tor pathway. Similarly, we find that in
      Caenorhabditis, the rate of amino acid replacement is lower for downstream genes.
      However, in Caenorhabditis, the rate of synonymous substitution is also strongly
      affected by the position of a gene in the pathway, and we show that the
      distribution of selective pressure along the pathway is driven by differential
      expression level. A full understanding of the effect of pathway structure on
      selective constraints is therefore likely to require inclusion of specific
      biological function into more general network models.

PMID- 21849327
TI  - Development of a web-based CT dose calculator: WAZA-ARI.
AB  - A web-based computed tomography (CT) dose calculation system (WAZA-ARI) is being
      developed based on the modern techniques for the radiation transport simulation
      and for software implementation. Dose coefficients were calculated in a voxel
      type Japanese adult male phantom (JM phantom), using the Particle and Heavy Ion
      Transport code System. In the Monte Carlo simulation, the phantom was irradiated
      with a 5-mm-thick, fan-shaped photon beam rotating in a plane normal to the body
      axis. The dose coefficients were integrated into the system, which runs as Java
      servlets within Apache Tomcat. Output of WAZA-ARI for GE LightSpeed 16 was
      compared with the dose values calculated similarly using MIRD and ICRP Adult Male
      phantoms. There are some differences due to the phantom configuration,
      demonstrating the significance of the dose calculation with appropriate phantoms.
      While the dose coefficients are currently available only for limited CT scanner
      models and scanning options, WAZA-ARI will be a useful tool in clinical practice
      when development is finalised.

PMID- 21849329
TI  - Pediatric high-grade glioma: identification of poly(ADP-ribose) polymerase as a
      potential therapeutic target.
AB  - Pediatric high-grade gliomas (World Health Organization grades III and IV
      astrocytomas) remain tumors with a very poor prognosis for which novel
      therapeutic strategies are needed. Poly(ADP-ribose) polymerase (PARP) is known to
      have multiple functions in tumors, including single-strand DNA repair and
      induction of caspase-independent apoptosis. PARP has been suggested as a
      therapeutic target in adult malignancies, and this study examines whether it
      could also be a potential target in pediatric high-grade glioma. Tissue
      microarrays containing 150 formalin-fixed pediatric high-grade gliomas were
      examined by immunohistochemistry for levels of PARP and expression of apoptosis
      inducing factor (AIF). Full retrospective clinical and survival data were
      available for this cohort. Stratification and statistical analysis was performed
      to assess the effect of PARP status on prognosis. The level of PARP
      immunopositivity had a statistically significant inverse correlation (P = .019)
      with survival in supratentorial pediatric high-grade glioma. AIF staining was
      notable for its absence in the majority of tumors but with moderate levels of
      expression in surrounding normal brain. PARP is expressed at high levels in many
      pediatric high-grade gliomas, and in these tumors, the ability of PARP to
      activate AIF appears to have been lost. PARP may therefore represent a promising
      therapeutic target for these lesions and warrants evaluation in clinical trials.

PMID- 21849330
TI  - Right atrial free-floating thrombus in dilated cardiomyopathy.

PMID- 21849331
TI  - Effect of migraine treatment on heart.

PMID- 21849332
TI  - Enabling distributed electronic research data collection for a rural Appalachian
      tobacco cessation study.
AB  - Tobacco use is increasingly prevalent among vulnerable populations, such as
      people living in rural Appalachian communities. Owing to limited access to a
      reliable internet service in such settings, there is no widespread adoption of
      electronic data capture tools for conducting community-based research. By
      integrating the REDCap data collection application with a custom synchronization
      tool, the authors have enabled a workflow in which field research staff located
      throughout the Ohio Appalachian region can electronically collect and share
      research data. In addition to allowing the study data to be exchanged in near
      real-time among the geographically distributed study staff and centralized study
      coordinator, the system architecture also ensures that the data are stored
      securely on encrypted laptops in the field and centrally behind the Ohio State
      University Medical Center enterprise firewall. The authors believe that this
      approach can be easily applied to other analogous study designs and settings.

PMID- 21849333
TI  - A global travelers' electronic health record template standard for personal
      health records.
AB  - Tourism as well as international business travel creates health risks for
      individuals and populations both in host societies and home countries. One
      strategy to reduce health-related risks to travelers is to provide travelers and
      relevant caregivers timely, ongoing access to their own health information. Many
      websites offer health advice for travelers. For example, the WHO and US
      Department of State offer up-to-date health information about countries relevant
      to travel. However, little has been done to assure travelers that their medical
      information is available at the right place and time when the need might arise.
      Applications of Information and Communication Technology (ICT) utilizing mobile
      phones for health management are promising tools both for the delivery of
      healthcare services and the promotion of personal health. This paper describes
      the project developed by international informaticians under the umbrella of the
      International Medical Informatics Association. A template capable of becoming an
      international standard is proposed. This application is available free to anyone
      who is interested. Furthermore, its source code is made open.

PMID- 21849334
TI  - A framework for evaluating the appropriateness of clinical decision support
      alerts and responses.
AB  - OBJECTIVE: Alerting systems, a type of clinical decision support, are
      increasingly prevalent in healthcare, yet few studies have concurrently measured
      the appropriateness of alerts with provider responses to alerts. Recent reports
      of suboptimal alert system design and implementation highlight the need for
      better evaluation to inform future designs. The authors present a comprehensive
      framework for evaluating the clinical appropriateness of synchronous,
      interruptive medication safety alerts. METHODS: Through literature review and
      iterative testing, metrics were developed that describe successes, justifiable
      overrides, provider non-adherence, and unintended adverse consequences of
      clinical decision support alerts. The framework was validated by applying it to a
      medication alerting system for patients with acute kidney injury (AKI). RESULTS:
      Through expert review, the framework assesses each alert episode for
      appropriateness of the alert display and the necessity and urgency of a clinical
      response. Primary outcomes of the framework include the false positive alert
      rate, alert override rate, provider non-adherence rate, and rate of provider
      response appropriateness. Application of the framework to evaluate an existing
      AKI medication alerting system provided a more complete understanding of the
      process outcomes measured in the AKI medication alerting system. The authors
      confirmed that previous alerts and provider responses were most often
      appropriate. CONCLUSION: The new evaluation model offers a potentially effective
      method for assessing the clinical appropriateness of synchronous interruptive
      medication alerts prior to evaluating patient outcomes in a comparative trial.
      More work can determine the generalizability of the framework for use in other
      settings and other alert types.

PMID- 21849335
TI  - Combination therapy for the treatment of pulmonary arterial hypertension.
AB  - Multiple medical therapies have been developed for the treatment of pulmonary
      arterial hypertension (PAH) over the last decade and a half. Unfortunately, none
      of these medications is curative and the majority of patients develop disease
      progression despite treatment. Presently available medications target one of
      three known pathways that have been implicated in disease pathogenesis. The
      multiplicity of pulmonary vascular abnormalities identified in PAH provides the
      rationale for a therapeutic strategy that targets more than one mechanism at a
      time. Although a handful of studies have demonstrated clinical improvement in PAH
      patients who have a second medication added to stable background therapy in a
      randomized, placebo-controlled fashion, it is unclear whether the derived benefit
      is due to the combination of two therapies or merely the response to the new
      agent. This review discusses the rationale for combination therapy, critically
      reviews the findings of presently completed combination studies and outlines the
      need for new studies that are better designed to determine whether combination
      therapy is more efficacious than single agent therapies for the treatment of PAH.

PMID- 21849336
TI  - The ability of a behaviour-specific patient questionnaire to identify poorly
      performing doctors.
AB  - BACKGROUND: Doctors' ability to communicate with patients varies. Patient
      questionnaires are often used to assess doctors' communication skills. OBJECTIVE:
      To investigate whether the Four Habits Patient Questionnaire (4HPQ) can be used
      to assess the different skill levels of doctors. DESIGN: A cross-sectional study
      of 497 hospital encounters with 71 doctors. Encounters were videotaped and
      patients completed three post-visit questionnaires. SETTING: A 500-bed general
      teaching hospital in Norway. MAIN OUTCOME: The proportion of video-observed
      between-doctor variance that could be predicted by 4HPQ. RESULTS: There were
      strong correlations between all patient-reported outcomes (range 0.71-0.80 at the
      doctor level, p < 0.01). 4HPQ correlated significantly with video-observed
      behaviour at the doctor level (Pearson's r = 0.42, p<0.01) and the encounter
      level (Pearson's r = 0.27, p < 0.01). The proportion of between-doctor variance
      not detectable by 4HPQ was 88%. The reason for this discordance was large within
      doctor between-encounter variance observed in the videos, and small between
      patient variance in patient reports. The maximum positive predictive value for
      the identification of poorly performing doctors (92%) was achieved with a cut-off
      score for 4HPQ of 82% (ie, patient assessments were concordant with expert
      observers for these doctors). CONCLUSION: Using a patient-reported questionnaire
      of doctors' communication skills, favourable assessments of doctors by patients
      were mostly discordant with the views of expert observers. Only very poor
      performance identified by patients was in agreement with the views of expert
      observers. The results suggest that patient reports alone may not be sufficient
      to identify all doctors whose communication skills need improvement training.

PMID- 21849337
TI  - Feasibility study to assess the use of the Cincinnati stroke scale by emergency
      medical dispatchers: a pilot study.
AB  - The emergency medical dispatcher (EMD) receiving a call via 911 is the first
      point of contact within the acute care system and plays an important role in
      early stroke recognition. Published studies show that the diagnostic accuracy of
      stroke of EMD needs to be improved. Therefore, the National Association of
      Emergency Medical Dispatchers implemented a stroke diagnostic tool modelled after
      the Cincinnati stroke scale across 3000 cities worldwide. This is the first time
      a diagnostic tool that requires callers to test physical findings and report
      those back to the EMD has been implemented. However, the ability of EMD and 911
      callers to use this in real time has not been reported. The goal of this pilot
      study was to determine the feasibility of an EMD applying the Cincinnati stroke
      scale tool during a 911 call, and to report the time required to administer the
      tool.

PMID- 21849338
TI  - Using atypical symptoms and red flags to identify non-demyelinating disease.
AB  - BACKGROUND: Red flags and atypical symptoms have been described as being useful
      in suggesting alternative diagnoses to multiple sclerosis (MS) and clinically
      isolated syndrome (CIS); however, their diagnostic utility has not been assessed.
      The aim of this study was to establish the predictive value of red flags and the
      typicality/atypicality of symptoms at presentation in relation to the final
      diagnosis of patients referred with suspected MS. METHODS: All patients referred
      with suspected MS over a 3-year period were assessed by the typicality of the
      clinical presentation and the occurrence of red flags in relation to the eventual
      diagnosis. The extent of agreement of trainee and consultant neurologists as to
      typicality of clinical presentations was determined. RESULTS: Of 244 patients
      referred, 119 (49%) had MS/CIS and 125 (51%) did not. 41 patients were referred
      because of an abnormal MRI. Of 203 with clinical symptoms, 96 patients had
      atypical symptoms of whom, 81 (84%) did not have MS and 15 (16%) had MS/CIS.
      Typical symptoms occurred in 107 patients; 10% did not have MS/CIS. Atypical
      symptoms had a sensitivity of 84%, specificity of 90% and positive likelihood
      ratio (PLR) of 8.4, whereas red flags had a sensitivity of 47%, specificity of
      88% and PLR of 3.9 for the exclusion of MS/CIS. Mean percentage agreement between
      consultants and trainees was 73% with a range of 32-96%. CONCLUSIONS: Atypical
      features at presentation are more sensitive, specific and have a higher PLR than
      red flags to refute a diagnosis of MS/CIS.

PMID- 21849339
TI  - Non-invasive ventilation in motor neuron disease: an update of current UK
      practice.
AB  - BACKGROUND: In motor neurone disease (MND), respiratory muscle weakness causes
      substantial morbidity, and death is usually due to respiratory failure. Non
      invasive ventilation (NIV) improves symptoms, quality of life and survival, but
      previous surveys showed that few patients with MND received NIV. METHODS: A
      postal survey was conducted of the clinical application of NIV in MND among
      consultant neurologists in the UK. The results were compared with those of a
      similar survey done in 2000. FINDINGS: Over 12 months, 612 patients were referred
      for NIV of whom 444 were successfully established on treatment (72.5% success
      rate). 38% of responding neurologists assessed respiratory function at
      presentation and 20% routinely monitored respiratory function; 32% relied on
      symptoms as the only criterion for NIV referral and 43% used a combination of
      symptoms and physiological impairment. 75% of responding neurologists accessed
      specialist palliative care services for their patients towards the end of life
      and 69% at an earlier stage. INTERPRETATION: Compared with 2000, there has been a
      marked increase in the number of patients referred for, and currently using, NIV
      (2.6 and 3.4-fold, respectively). The proportion successfully established on NIV
      has also increased, suggesting more appropriate selection and/or improvement in
      the methods of using NIV in this challenging group of patients. However,
      monitoring of respiratory function is suboptimal and uncontrolled oxygen is
      sometimes used inappropriately before the terminal phase.

PMID- 21849340
TI  - Distinct neuropsychological profiles correspond to distribution of cortical
      thinning in inherited prion disease caused by insertional mutation.
AB  - BACKGROUND: The human prion diseases are a group of universally fatal
      neurodegenerative disorders associated with the auto-catalytic misfolding of the
      normal cell surface prion protein (PrP). Mutations causative of inherited human
      prion disease (IPD) include an insertion of six additional octapeptide repeats (6
      OPRI) and a missense mutation (P102L) with large families segregating for each
      mutation residing in southern England. Here we report for the first time the
      neuropsychological and clinical assessments in these two groups. METHOD: The
      cognitive profiles addressing all major domains were obtained for 26 patients (18
      6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset
      of 10 (six 6-OPRI, four P102L). RESULTS: The cognitive profiles were different in
      patients with the two mutations in the symptomatic phase of the disease. The 6
      OPRI group had lower premorbid optimal levels of functioning (assessed on the
      NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI
      patients had significantly more executive dysfunction than the P102L group and
      were more impaired on tests of perception and nominal functions. There was
      anecdotal evidence of low premorbid social performance in the 6-OPRI but not
      P102L patients. Cortical thinning distribution correlated with the
      neuropsychological profile in the 6-OPRI group principally involving the
      parietal, occipital and posterior frontal regions. The small number of patients
      in the P102L group precluded statistical comparison between the groups.
      CONCLUSIONS: The 6-OPRI patients had more widespread and severe cognitive
      dysfunction than the P102L group and this correlated with cortical thinning
      distribution.

PMID- 21849341
TI  - Manual material handling advice and assistive devices for preventing and treating
      back pain in workers: a Cochrane Systematic Review.

PMID- 21849342
TI  - Why do women and men have different occupational exposures?

PMID- 21849343
TI  - Risk of tuberculosis and fuel use: a population study.

PMID- 21849344
TI  - Forest fires are associated with elevated mortality in a dense urban setting.
AB  - OBJECTIVES: The climate and vegetation of the greater Athens area (population
      over three million) make forest fires a real threat to the environment during the
      summer. A few studies have reported the adverse health effects of forest fires,
      mainly using morbidity outcomes. The authors investigated the short-term effects
      of forest fires on non-accidental mortality in the population of Athens, Greece,
      during 1998-2004. METHODS: The authors used generalised additive models to
      investigate the effect of forest fires on daily mortality, adjusting for time
      trend and meteorological variables, taking into account air pollution as measured
      from fixed monitors. Forest fires were classified by size according to the area
      burnt. RESULTS: Small fires do not have an effect on mortality. Medium sized
      fires are associated with an increase of 4.9% (95% CI 0.3% to 9.6%) in the daily
      total number of deaths, 6.0% (95% CI -0.3% to 12.6%) in the number of
      cardiovascular deaths and 16.2% (95% CI 1.3% to 33.4%) in the number of
      respiratory deaths. Cardiovascular effects are larger in those aged <75 years,
      while respiratory effects are larger in older people. The corresponding effects
      of the one large fire are: 49.7% (95% CI 37.2% to 63.4%), 60.6% (95% CI 43.1% to
      80.3%) and 92.0% (95% CI 47.5% to 150.0%). These effects cannot be completely
      explained by an increase in ambient particle concentrations. CONCLUSION: Forest
      fires have an immediate effect on mortality, not associated with accidental
      deaths, which is a significant public health problem, especially if the fire
      occurs near a densely populated area.

PMID- 21849345
TI  - Effects of job strain on fatigue: cross-sectional and prospective views of the
      job content questionnaire and effort--reward imbalance in the GAZEL cohort.
AB  - OBJECTIVES: The objectives this study were (1) to investigate correlations
      between measures of psychosocial workplace stress as measured in separate years
      by the Job Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) scales;
      (2) to establish a valid measure of psychosocial job stress with its components
      (by identifying the individual and interactive associations of job stress
      components) and (3) to use the component measures to assess the risk of
      psychosocial strain at work on fatigue. METHODS: The JCQ and ERI from the annual
      survey of the GAZEL cohort established in 1989 initially with 20,624 respondents
      were used to investigate the associations of workplace stress on mental and
      physical fatigue in two separate years (1998 and 2006). First, the JCQ measures
      from separate years (1997 and 1999) were combined to create a measure for the
      same year as ERI (1998). The new measure was validated for internal and external
      consistency. Using logistic regression, the subcomponents of stress (upper
      tertiles of psychological demands, physical demands, decision latitude, social
      support, effort, reward, ERI and overcommitment) were tested for associations
      with the highest reporting of mental and physical fatigue. RESULTS: By combining
      JCQ responses from 1997 to 1999, we were able to increase the amount of
      information available on psychosocial factors in 1998. Psychometric properties of
      the workplace stress scales also showed expected factor loadings. Workplace
      psychosocial factors had greater associations with fatigue among men than women.
      Although psychosocial factors became less predictive of fatigue at 8 years of
      follow-up, associations between fatigue and psychosocial components
      (overcommitment, social support and rewards) remained significant. CONCLUSIONS:
      These analyses continue to validate the various subcomponents scales of workplace
      stress as measured by the JCQ and effort-reward imbalance model in GAZEL. They
      also highlight the importance of psychosocial work factors in the experience of
      overall fatigue even after an 8-year follow-up.

PMID- 21849346
TI  - A proposed threshold exposure for airborne asbestos.

PMID- 21849347
TI  - Has European Union legislation to reduce exposure to chromate in cement been
      effective in reducing the incidence of allergic contact dermatitis attributed to
      chromate in the UK?
AB  - OBJECTIVE: Hexavalent chromate (chromate) in cement is a well-recognised cause of
      allergic contact dermatitis (ACD). Consequently in January 2005, following
      European Union legislation (EU Directive 2003/53/EC), the use or supply of cement
      containing >2 ppm of chromate was prohibited in the UK (COSHH 2004). This
      analysis of work-related ill-health surveillance aims to evaluate the
      effectiveness of this legislation. METHOD: Changes in the incidence of work
      related ACD cases returned to The Health and Occupation Reporting network by
      dermatologists were analysed taking in to account attribution to chromate and
      occupation. RESULTS: There was a significant decline in the incidence of both ACD
      attributed to chromate (incidence rate ratio 0.48, 95% CI 0.36 to 0.64) and ACD
      not-attributed chromate (0.76, 95% CI 0.69 to 0.85) between the time period
      preceding the EU legislation (2002-2004) and the postlegislation period (2005
      2009). However, the decline in ACD attributed to chromate was significantly
      greater (p=0.006). This decline was further increased in workers potentially
      exposed to cement (incidence rate ratio 0.37, p=0.001). The majority of the
      decline in incidence occurred during 2005. CONCLUSION: The timing of this
      significant decline in the UK incidence of chromate attributed ACD, and the
      greater decline in workers potentially exposed to cement strongly suggests that
      the EU Directive2003/53/EC was successful in reducing exposure to chromate in
      cement in the UK.

PMID- 21849348
TI  - Socioeconomic disadvantage affects course and recurrence of psychiatric
      disability.

PMID- 21849349
TI  - Early retinal blood vessel growth in normal and growth restricted rat pups raised
      in oxygen and room air.
AB  - BACKGROUND/AIMS: Premature infants are born with incompletely vascularised
      retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of
      prenatal and postnatal body growth is important in the pathogenesis of ROP. The
      aim of this study was to develop a physiology-based rat model in order to study
      the effect of growth restriction and oxygen on early retinal vascular
      development. METHODS: Rat mothers were fed either a normal (18% casein) or low
      (9% casein) protein diet (to cause pup growth restriction) from the last week of
      gestation. After birth, mother and pups were placed in either room air or a
      specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen
      profile. The oxygen profile was based on that from a premature infant who
      developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained
      using biotinylated lectin. Images were captured by confocal microscopy. The
      avascular areas of the retinas were measured and compared. RESULTS: Growth
      restricted rat pups had significantly larger retinal avascular areas than
      'normally grown' rat pups (Mann-Whitney U test, p<0.001). Growth restricted rat
      pups raised in fluctuating oxygen had significantly larger retinal avascular
      areas than growth restricted rat pups raised in room air (Mann-Whitney U test,
      p=0.001). CONCLUSIONS: The authors have developed a novel model for ROP that
      involves inducing both intrauterine and postnatal growth restriction and also
      exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can
      be used to study the effects of growth, nutrition and oxygen on early retinal
      vascular development.

PMID- 21849350
TI  - Effect of inner retinal dysfunction on slow double-stimulation multifocal
      electroretinogram.
AB  - PURPOSE: This study investigated the retinal adaptive mechanism in inner retinal
      dysfunction using the slow double-stimulation multifocal electroretinogram
      (mfERG) paradigm. METHODS: Slow double-stimulation mfERG responses were recorded
      from 15 eyes of 15 4-month-old Mongolian gerbils in control conditions and after
      suppression of inner retinal responses with injections of tetrodotoxin (TTX) and
      N-methyl-d-aspartic acid (NMDA). The stimulation consisted of five video frames:
      the two initial frames with multifocal flashes were triggered by two independent
      m-sequences, followed by three dark video frames. The results were compared with
      findings in humans: 7 subjects with glaucoma and 31 age-matched normal subjects
      were measured using the same mfERG protocol. RESULTS: The stimulation generates
      two responses (M(1) and M(2)) from the two independent multifocal frames. The
      M(1):M(2) ratio showed a significant reduction after administration of TTX+NMDA
      in the animal study. This matched with the human glaucoma findings. Glaucoma
      subjects generally have a reduced M(1):M(2) ratio; this ratio showed a
      sensitivity of 86%, with a specificity of 84% for differentiating normal eyes
      from glaucomatous eyes. CONCLUSION: This stimulation paradigm provides a method
      of measuring temporal visual characteristics. The M(1):M(2) ratio acts as an
      indirect functional indicator of retinal adaptation, which may be abnormal in the
      diseased retina. Further development of this method may help to describe the
      functional variation in the diseased retina and to predict the occurrence of a
      range of retinopathies.

PMID- 21849351
TI  - Baroreflex deficiency hampers angiogenesis after myocardial infarction via
      acetylcholine-alpha7-nicotinic ACh receptor in rats.
AB  - AIMS: Angiogenesis is critical for re-establishing blood supply to ischaemic
      myocardium after myocardial infarction (MI). Human studies have associated
      arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI.
      The present work was designed to examine whether ABR deficiency affects
      angiogenesis in MI rats. METHODS AND RESULTS: Baroreflex sensitivity (BRS) was
      determined in conscious rats at 1 month after occlusion of the left anterior
      descending coronary artery. The survival time was significantly shorter in
      Sprague-Dawley rats with BRS <0.60 ms/mmHg vs. those with BRS >=0.60 ms/mmHg.
      Sinoaortic denervation destroyed ABR, and decreased capillary density, regional
      blood flow and vascular endothelial growth factor (VEGF) concentration after MI.
      Ketanserin (0.6 mg/kg/day) enhanced BRS, and increased capillary density,
      regional blood flow, and VEGF. Sinoaortic denervation also reduced the expression
      of vesicular acetylcholine (ACh) transporter and alpha7-nicotinic ACh receptor
      (alpha7-nAChR). Angiogenesis after MI was significantly attenuated in alpha7
      nAChR knockout mice. In contrast, increase in endogenous ACh with cholinesterase
      inhibitor pyridostigmine (30 mg/kg/day) increased angiogenesis after MI. In
      cultured cardiac microvascular endothelial cells, ACh stimulated the expression
      of VEGF, phosphorylation of VEGF receptor 2, and tube formation in a manner
      dependent upon alpha7-nAChR. CONCLUSION: Our results demonstrated that ABR
      deficiency could attenuate angiogenesis in ischaemic myocardium. These findings
      provide further mechanistic basis for enhancing baroreflex function in the
      treatment of MI.

PMID- 21849353
TI  - Testing for seasonality using circular distributions based on non-negative
      trigonometric sums as alternative hypotheses.
AB  - In medical and epidemiological studies, the importance of detecting seasonal
      patterns in the occurrence of diseases makes testing for seasonality highly
      relevant. There are different parametric and non-parametric tests for
      seasonality. One of the most widely used parametric tests in the medical
      literature is the Edwards test. The Edwards test considers a parametric
      alternative that is a sinusoidal curve with one peak and one trough. The Cave and
      Freedman test is an extension of the Edwards test that is also frequently applied
      and considers a sinusoidal curve with two peaks and two troughs as the
      alternative hypothesis. The Kuiper, Hewitt and David and Newell are common non
      parametric tests. Fernandez-Duran (2004) developed a family of univariate
      circular distributions based on non-negative trigonometric (Fourier) sums
      (series) (NNTS) that can account for an arbitrary number of peaks and troughs. In
      this article, this family of distributions is used to construct a likelihood
      ratio test for seasonality considering parametric alternative hypotheses that are
      NNTS distributions.

PMID- 21849354
TI  - Comments on 'A hierarchical zero-inflated log-normal model for skewed responses'.

PMID- 21849352
TI  - Granulocyte colony-stimulating factor treatment plus dipeptidylpeptidase-IV
      inhibition augments myocardial regeneration in mice expressing cyclin D2 in adult
      cardiomyocytes.
AB  - AIMS: Although pharmacological interventions that mobilize stem cells and enhance
      their homing to damaged tissue can limit adverse post-myocardial infarction (MI)
      remodelling, cardiomyocyte renewal with this approach is limited. While
      experimental cell cycle induction can promote cardiomyocyte renewal following MI,
      this process must compete with the more rapid processes of scar formation and
      adverse remodelling. The current study tested the hypothesis that the combination
      of enhanced stem cell mobilization/homing and cardiomyocyte cell cycle induction
      would result in increased myocardial renewal in injured hearts. METHODS AND
      RESULTS: Myocardial infarction was induced by coronary artery ligation in adult
      MHC-cycD2 transgenic mice (which exhibit constitutive cardiomyocyte cell cycle
      activity) and their non-transgenic littermates. Mice were then treated with
      saline or with granulocyte colony-stimulating factor (G-CSF) plus the
      dipeptidylpeptidase-IV (DPP-IV) inhibitor Diprotin A (DipA) for 7 days. Infarct
      thickness and cardiomyocyte number/infarct/section were significantly improved in
      MHC-cycD2 mice with G-CSF plus DipA treatment when compared with MHC-cycD2
      transgene expression or G-CSF plus DipA treatment alone. Echocardiographic
      analyses revealed that stem cell mobilization/homing and cardiomyocyte cell cycle
      activation had an additive effect on functional recovery. CONCLUSION: These data
      strongly suggest that G-CSF plus DPP-IV inhibition, combined with cardiomyocyte
      cell cycle activation, leads to enhanced myocardial regeneration following MI.
      The data are also consistent with the notion that altering adverse post-injury
      remodelling renders the myocardium more permissive for cardiomyocyte
      repopulation.

PMID- 21849356
TI  - Not the typical Tornwaldt's cyst this time? A nasopharyngeal cyst associated with
      canalis basilaris medianus.
AB  - We report a patient with a cystic structure in the nasopharynx mimicking a
      Tornwaldt's cyst, which was felt to represent a different entity owing to the
      lack of the distinct features of a typical Tornwaldt's cyst. It was associated
      with a bony cleft in the basiocciput that was considered to be a canalis
      basilaris medianus (CBM), thought to represent an embryological vestige of the
      cephalic end of the notochord along its course within the basiocciput.

PMID- 21849357
TI  - Differentiating osteoradionecrosis from nasopharyngeal carcinoma tumour
      recurrence using 99Tcm-sestamibi SPECT/CT.
AB  - Osteoradionecrosis (ORN) of the base of skull is a known complication of external
      beam radiotherapy in the treatment of nasopharyngeal carcinoma, and is widely
      believed to be sequelae of radiation-induced endarteritis, leading to cellular
      death and fibrosis. Differentiating ORN from tumour recurrence is challenging and
      has direct clinical implications. We present a case where (99)Tc(m)-sestamibi
      SPECT/CT was used to differentiate ORN from tumour recurrence and in which prior
      imaging using bone scintigraphy and fluorodeoxyglucose PET/CT were equivocal.

PMID- 21849359
TI  - Diffusion MRI findings of cytomegalovirus-associated ventriculitis: a case
      report.
AB  - Cytomegalovirus (CMV) ventriculoencephalitis is a rare but serious potential
      complication of CMV infection in immunocompromised patients. Characteristic
      diffusion-weighted imaging findings can be helpful for the diagnosis of CMV
      ventriculitis, as in this case report.

PMID- 21849358
TI  - Vanishing bone metastases--a pitfall in the interpretation of contrast enhanced
      CT in patients with superior vena cava obstruction.
AB  - We describe a previously unreported case of vertebral marrow enhancement owing to
      collateral circulation in a patient with superior vena cava obstruction. Failure
      to recognise this phenomenon led to the misdiagnosis of sclerotic bone
      metastases.

PMID- 21849360
TI  - Uptake of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid in
      metastatic adrenal tumour from hepatocellular carcinoma.
AB  - We present the case of a metastatic adrenal tumour from hepatocellular carcinoma
      (HCC) showing the uptake of gadolinium ethoxybenzyl diethylenetriaminepentaacetic
      acid (Gd-EOB-DTPA) on MRI. To our knowledge, this is the first case of metastatic
      HCC in which Gd-EOB-DTPA uptake was shown on MRI and this finding facilitated the
      accurate pre-operative diagnosis of a metastatic adrenal tumour.

PMID- 21849361
TI  - Imaging findings of a primary bladder maltoma.
AB  - Secondary involvement of the urinary bladder in non-Hodgkin's lymphoma is
      relatively common; however, primary malignant lymphoma of this organ is extremely
      rare. The most common type of primary bladder lymphoma is a low-grade B-cell
      mucosa-associated lymphoid tissue (MALT) lymphoma. We report here on the imaging
      findings of a primary bladder lymphoma with bone marrow infiltration.

PMID- 21849362
TI  - MRI conditional pacemakers: the start of a new era.

PMID- 21849363
TI  - MRI of retinoblastoma.
AB  - We review the role of MRI in retinoblastoma and simulating lesions.
      Retinoblastoma is the most common paediatric intra-ocular tumour. It may be
      endophytic, exophytic or a diffuse infiltrating tumour. MRI can detect intra
      ocular, extra-ocular and intracranial extension of the tumour. MRI is essential
      for monitoring patients after treatment and detection of associated second
      malignancies. It helps to differentiating the tumour from simulating lesions with
      leukocoria.

PMID- 21849364
TI  - Lowering heart rate with an optimised breathing protocol for prospectively ECG
      triggered CT coronary angiography.
AB  - OBJECTIVES: The aim was to prospectively characterise the effect of the level of
      breath-hold on heart rate in CT coronary angiography (CTCA) with prospective
      electrocardiogram (ECG) triggering and its impact on coronary artery attenuation.
      METHODS: 260 patients (86 women; mean age 59 +/- 11 years) underwent 64-slice
      CTCA using prospective ECG triggering. Prior to CTCA, heart rates were recorded
      during 15 s of breath-hold at three different levels of inspiration (normal,
      intermediate and deep). The inspiration level with the lowest heart rate was
      chosen for actual CTCA scanning. Coronary artery attenuation was measured, and
      the presence of backflow of contrast material into the inferior vena cava (as an
      indicator of increased intrathoracic pressure) was recorded. RESULTS: The mean
      heart rate at breath-hold was significantly different for the three inspiration
      levels (normal, 60 +/- 8 bpm; intermediate, 59 +/- 8 bpm; deep, 57 +/- 7 bpm;
      p<0.001). The maximum heart rate reduction in each patient at breath-hold
      averaged 5.3 +/- 5.1 bpm, and was observed at a normal inspiration depth in 23
      (9%) patients, at an intermediate inspiration depth in 102 (39%) patients and at
      deep inspiration in 135 (52%) patients. Overall, there was no association between
      the level of breath-hold and coronary vessel attenuation (p-value was not
      significant). However, the backflow of contrast material into the inferior vena
      cava (n = 26) was found predominantly at deep inspiration levels (p<0.001), and,
      when it occurred, it was associated with reduced coronary attenuation compared
      with patients with no backflow (p<0.05). CONCLUSION: The breath-hold level to
      best reduce heart rate for CTCA should be individually assessed prior to scanning
      because a mean heart rate reduction of 5 bpm can be achieved.

PMID- 21849365
TI  - Head and neck MRI of Kimura disease.
AB  - OBJECTIVES: The purpose of our study was to describe the MR appearance of Kimura
      disease and to interpret the differences in appearance from malignant parotid
      gland tumours. METHODS: MR studies of seven patients with Kimura disease were
      reviewed. The MR studies included T(1) weighted, T(2) weighted, short tau
      inversion-recovery, diffusion-weighted (DW) and dynamic contrast-enhanced
      imaging. RESULTS: Typical Kimura disease featured subcutaneous lesions,
      continuously infiltrated parotid lesions from the subcutaneous lesions with or
      without intraparotid lymphadenopathies, and reactive cervical lymphadenopathies.
      The subcutaneous lesions showed gradual upward enhancement on dynamic contrast
      enhanced MR images. Reactive lymph nodes showed early enhancement on contrast
      enhanced MR images and marked high intensity and low apparent diffusion
      coefficient values on DW images. CONCLUSION: An indication for making the
      diagnosis of Kimura disease should be the subcutaneous tissue of the head and
      neck showing gradual upward enhancement on dynamic contrast-enhanced MRI and a
      lack of high intensity on DW images, associated with reactive lymph nodes.

PMID- 21849366
TI  - Preliminary experience of a predictive model to define rectal volume and rectal
      dose during the treatment of prostate cancer.
AB  - OBJECTIVES: The aim of this study was to define a method to evaluate the total
      dose delivered to the rectum during the whole treatment course in six patients
      undergoing irradiation for prostate cancer using an offline definition of organ
      motion with images from a cone beam CT (CBCT) scanner available on a commercial
      linear accelerator. METHODS: Patient set-up was verified using a volumetric three
      dimensional CBCT scanner; 9-14 CBCT scans were obtained for each patient. Images
      were transferred to a commercial treatment planning system for offline organ
      motion analysis. The shape of the rectums were used to obtain a mean dose-volume
      histogram (<DVH>), which was the average of the DVHs of the rectums as they
      appeared in each verification CBCT. A geometric model of an average rectum (AR)
      was produced using the rectal contours delineated on the CBCT scans (DVH(AR)). To
      check whether the first week of treatment was representative of the whole
      treatment course, we evaluated the DVHs related to only the first five CBCT scans
      (<DVH5> and DVH(AR5)). Finally, the influence of a dietary protocol on the
      goodness of our results was considered. RESULTS: In all six patients the original
      rectal DVH for the planning CT scan showed higher values than all DVHs.
      CONCLUSION: Although the application of the model to a larger set of patients is
      necessary to confirm this trend, reconstruction of a representative volume of the
      rectum throughout the entire treatment course seems feasible.

PMID- 21849367
TI  - Biodosimetric quantification of short-term synchrotron microbeam versus broad
      beam radiation damage to mouse skin using a dermatopathological scoring system.
AB  - OBJECTIVES: Microbeam radiotherapy (MRT) with wafers of microscopically narrow,
      synchrotron generated X-rays is being used for pre-clinical cancer trials in
      animal models. It has been shown that high dose MRT can be effective at
      destroying tumours in animal models, while causing unexpectedly little damage to
      normal tissue. The aim of this study was to use a dermatopathological scoring
      system to quantify and compare the acute biological response of normal mouse skin
      with microplanar and broad-beam (BB) radiation as a basis for biological
      dosimetry. METHOD: The skin flaps of three groups of mice were irradiated with
      high entrance doses (200 Gy, 400 Gy and 800 Gy) of MRT and BB and low dose BB (11
      Gy, 22 Gy and 44 Gy). The mice were culled at different time-points post
      irradiation. Skin sections were evaluated histologically using the following
      parameters: epidermal cell death, nuclear enlargement, spongiosis, hair follicle
      damage and dermal inflammation. The fields of irradiation were identified by
      gammaH2AX-positive immunostaining. RESULTS: The acute radiation damage in skin
      from high dose MRT was significantly lower than from high dose BB and,
      importantly, similar to low dose BB. CONCLUSION: The integrated MRT dose was more
      relevant than the peak or valley dose when comparing with BB fields. In MRT
      treated skin, the apoptotic cells of epidermis and hair follicles were not
      confined to the microbeam paths.

PMID- 21849369
TI  - MRI and cardiac pacing devices--beware the rules are changing.

PMID- 21849368
TI  - MRI-based pre-planning in patients with cervical cancer treated with three
      dimensional brachytherapy.
AB  - OBJECTIVE: The aim of this study was to analyse the feasibility and determine the
      benefits of MRI-based pre-planning with CT/MRI data fusion in patients with
      cervical cancer treated with radical radiotherapy. METHODS: Patients underwent
      MRI examination prior to external beam radiotherapy and prior to the first and
      fourth fraction of brachytherapy with applicators in place. Insertion of
      applicators at the radiology department was performed under paracervical
      anaesthesia. The benefit of MRI pre-planning was determined by comparing
      conventional treatment planning with dose specification to "point A" and dose
      specification to 90% of the high-risk clinical target volume (HR-CTV D90).
      Tolerance of MRI evaluation with applicators, coverage of HR-CTV and dose-volume
      parameters for organs at risk (OAR) has been assessed in 42 brachytherapy
      procedures. RESULTS: Insertion of applicators at the radiology department was
      successful in all patients and there were no complications. The target dose was
      higher for MRI planning than for conventional planning (5.3 Gy vs 4.5 Gy).
      Maximum doses in the bladder and rectum were significantly lower (p<0.05) for MRI
      planning than for the conventional approach (6.49 Gy vs 7.45 Gy for bladder; 4.57
      Gy vs 5.06 Gy for rectum). We found no correlation between the International
      Commission on Radiation Units (ICRU) point dose for OAR and the maximum dose in
      OAR. Nevertheless, a strong correlation between the maximum dose in OAR and the
      minimal dose in a volume of 2 cm(3) has been observed. CONCLUSION: MRI-based pre
      planning with consecutive CT/MRI data fusion is feasible and safe, with the
      advantage of increasing the dose to the tumour and decreasing the dose to the
      organs at risk.

PMID- 21849370
TI  - Review of congenital inner ear abnormalities on CT temporal bone.
AB  - The aetiology of profound hearing loss in children is complex and multifactorial.
      Congenital inner ear abnormality is a major cause of hearing loss in children. CT
      temporal bone imaging is the modality of choice in the investigation of hearing
      loss. Recognising the congenital abnormalities of the inner ear guides the
      clinician's management of the condition. This pictorial essay illustrates the
      congenital abnormalities of the inner ear on high resolution CT temporal bone
      images and correlation with developmental arrest during embryology.

PMID- 21849371
TI  - An unusual cause of persistent subcutaneous fluid collection.

PMID- 21849372
TI  - Letter to the editor: The electronic learning habits of radiology trainees in
      London and South East England.

PMID- 21849373
TI  - Pelvic floor muscle exercises utilizing trunk stabilization for treating
      postpartum urinary incontinence: randomized controlled pilot trial of supervised
      versus unsupervised training.
AB  - OBJECTIVE: To investigate the effect of supervised and unsupervised pelvic floor
      muscle exercises utilizing trunk stabilization for treating postpartum urinary
      incontinence and to compare the outcomes. DESIGN: Randomized, single-blind
      controlled study. SETTING: Outpatient rehabilitation hospital. SUBJECTS: Eighteen
      subjects with postpartum urinary incontinence. INTERVENTIONS: Subjects were
      randomized to either a supervised training group with verbal instruction from a
      physiotherapist, or an unsupervised training group after undergoing a supervised
      demonstration session. MAIN MEASURES: Bristol Female Lower Urinary Tract Symptom
      questionnaire (urinary symptoms and quality of life) and vaginal function test
      (maximal vaginal squeeze pressure and holding time) using a perineometer.
      RESULTS: The change values for urinary symptoms (-27.22 +/- 6.20 versus -18.22 +/
      5.49), quality of life (-5.33 +/- 2.96 versus -1.78 +/- 3.93), total score (
      32.56 +/- 8.17 versus -20.00 +/- 6.67), maximal vaginal squeeze pressure (18.96
      +/- 9.08 versus 2.67 +/- 3.64 mmHg), and holding time (11.32 +/- 3.17 versus 5.72
      +/- 2.29 seconds) were more improved in the supervised group than in the
      unsupervised group (P < 0.05). In the supervised group, significant differences
      were found for all variables between pre- and post-test values (P < 0.01),
      whereas the unsupervised group showed significant differences for urinary symptom
      score, total score and holding time between the pre- and post-test results (P <
      0.05). CONCLUSIONS: These findings suggest that exercising the pelvic floor
      muscles by utilizing trunk stabilization under physiotherapist supervision may be
      beneficial for the management of postpartum urinary incontinence.

PMID- 21849374
TI  - Effect of combined exercise training on physical and metabolic fitness in adults
      with intellectual disability: a controlled trial.
AB  - OBJECTIVE: Investigating the effect of combined aerobic and strength training on
      metabolic and physical fitness in adults with intellectual disabilities compared
      to endurance training and no training. DESIGN: A controlled trial with patients
      receiving either combined (COM), endurance (END) or no training (C). SETTING: Two
      centres for intellectual disabilities (Sterrenhuis, Brasschaat and Emiliani,
      Lokeren, Belgium). SUBJECTS: Forty-five adults with intellectual disabilities
      (mean age: 42 (9,2), mean body mass index (BMI): 24 (3,9), mean IQ: 56 (5,6)).
      INTERVENTION: Combined exercise training (n = 15) and endurance training (n = 15)
      twice a week for 70  minutes per session for 20 weeks and no training (n = 15).
      Groups were matched for age, sex and intellectual disability. MAIN MEASURES:
      Lipid profile, physical fitness (primary); blood pressure and body composition.
      RESULTS: Compared to no training, combined exercise training has significant
      positive effects on total cholesterol levels, aerobic capacity, muscle strength
      and resting systolic blood pressure, while endurance exercise training has
      significant effects on aerobic capacity and resting systolic blood pressure.
      Compared to endurance training, combined exercise training resulted in a
      significant better evolution of total cholesterol (mean differences: -18 versus 
      3 mg/dl), 1RM upper (+6 versus +1  kg) and lower limb (+25 versus +8  kg) and
      abdominal muscles (+15 versus +1  kg), hand grip strength (+9 versus +2  kg),
      muscle fatigue resistance (+11 versus +5  sec), sit-to-stand (+5 versus +2/30  
      sec) and systolic blood pressure (-15 versus -10 mmHg). CONCLUSION: This study
      revealed a tendency towards more beneficial effects of combined exercise training
      in adults with intellectual disability.

PMID- 21849375
TI  - A disability prevention programme for community-dwelling frail older persons.
AB  - OBJECTIVE: To describe and justify a primary care interdisciplinary programme for
      community-dwelling frail older people aimed to prevent disability. BACKGROUND:
      Disability is a negative outcome of frailty among older persons. Policy reports
      and research studies emphasize the need for programmes to reduce disability
      progression. Between 2008 and 2010 we developed such a programme. DEVELOPMENT:
      Following the Intervention Mapping protocol, a research team and a
      multidisciplinary professional developed the programme. Literature reviews and an
      expert meeting led to identification of basic elements, theory-based methods and
      practical tools. THE PROGRAMME: The general practitioner and the practice nurse
      comprise the core team that can be extended by other professionals such as
      occupational and physical therapist. The programme includes six steps: (1)
      screening, (2) assessment, (3) analysis and preliminary action plan, (4)
      agreement on an action plan, (5) execution of the action plan (toolbox parts) and
      (6) evaluation and follow-up. The main features are: identifying risks for
      developing disability and targeting risk factors using professional standards and
      the 5A Behavioural Change Model to support self management, and identifying
      problems in performing activities and enhancing meaningful activities based on
      the Model of Human Occupation. Screening, individual assessment, tailor-made and
      client-centred care, self-management support, case management and
      interdisciplinary cooperation are important principles in delivering the
      programme. DISCUSSION: The disability-prevention programme seems promising for
      addressing the needs of frail older people for independent living and for
      targeting risk factors. Its feasibility and effects are currently being tested in
      a randomized controlled trial.

PMID- 21849376
TI  - The effects of whole body vibration therapy on bone mineral density and leg
      muscle strength in older adults: a systematic review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis of randomized controlled trials
      was undertaken to determine whether whole body vibration improves bone mineral
      density and leg muscle strength in older adults. DATA SOURCES: Sources included
      MEDLINE, CINAHL, EMBASE, PEDro, PubMed, Science Citation Index and the reference
      list of each eligible article. REVIEW METHODS: Article search and selection was
      performed independently by two researchers. The methodological quality of each
      selected article was rated by the PEDro scale. RESULTS: Thirteen randomized
      trials (18 articles) totalling 896 subjects fulfilled the selection criteria.
      Four were considered to have good or excellent methodological quality and the
      rest were rated as fair. Meta-analyses revealed that whole body vibration has no
      significant effect on hip or lumbar spine bone mineral density in older women
      when compared with no intervention or active exercise (P > 0.05). Whole body
      vibration, however, had a significant treatment effect on knee extension dynamic
      strength (standardized mean difference = 0.63, P = 0.006), leg extension
      isometric strength (standardized mean difference = 0.57, P = 0.003), and
      functional measures of leg muscle strength such as jumping height (standardized
      mean difference = 0.51, P = 0.010) and performance in sit-to-stand (standardized
      mean difference = 0.72, P < 0.001) among older adults compared with no
      intervention. CONCLUSION: Whole body vibration is beneficial for enhancing leg
      muscle strength among older adults. However, the review suggests that whole body
      vibration has no overall treatment effect on bone mineral density in older women.
      No randomized trial has examined the effects of whole body vibration on bone
      mineral density in older men.

PMID- 21849377
TI  - Effects of new, individually adjusted, progressive balance group training for
      elderly people with fear of falling and tend to fall: a randomized controlled
      trial.
AB  - OBJECTIVE: To evaluate the effects of a new, individually adjusted, progressive
      and specific balance group training programme on fear of falling, step execution,
      and gait in healthy elderly people with fear of falling and tend to fall. DESIGN:
      Randomized controlled trial. SETTING: The study was conducted in Stockholm
      County, Sweden. SUBJECTS: Fifty-nine community dwelling elderly people were
      recruited by advertisement, and allocated at random to an intervention group (n =
      38) or a control group (n = 21). INTERVENTION: Individually adjusted, progressive
      and specific balance group training was given three times a week for three
      months. The training incorporated elements included in, and required for,
      independent activities of daily living, and for reactions to loss of balance
      during dual or multiple tasks. MAIN MEASURES: Fear of falling was assessed with
      Falls Efficacy Scale International (FES-I). The reaction time of step execution
      was measured with the step-execution test, and gait was measured with
      GAITRite(r). RESULTS: After three months the intervention group showed
      significant positive changes in the FES-I (P = 0.008), in the step-execution
      phase of dual-task performance (P = 0.012), and in gait at preferred speed during
      single-task performance; in cadence (P = 0.030) and, at fast speed, in velocity
      (P = 0.004) and cadence (P = 0.001). Significant decreases were also found for
      the likelihood of depression after participating in the training programme.
      CONCLUSION: This new balance training programme is feasible and leads to
      decreased fear of falling, decreased time for step execution during dual-task
      performance and increased velocity during fast walking.

PMID- 21849378
TI  - Anorexia in young children: press coverage was flawed.

PMID- 21849379
TI  - A dead cert: what we might learn at the bookmakers.

PMID- 21849380
TI  - Opt in not out.

PMID- 21849381
TI  - A sick society?

PMID- 21849382
TI  - Butterfly proboscis: combining a drinking straw with a nanosponge facilitated
      diversification of feeding habits.
AB  - The ability of Lepidoptera, or butterflies and moths, to drink liquids from
      rotting fruit and wet soil, as well as nectar from floral tubes, raises the
      question of whether the conventional view of the proboscis as a drinking straw
      can account for the withdrawal of fluids from porous substrates or of films and
      droplets from floral tubes. We discovered that the proboscis promotes capillary
      pull of liquids from diverse sources owing to a hierarchical pore structure
      spanning nano- and microscales. X-ray phase-contrast imaging reveals that Plateau
      instability causes liquid bridges to form in the food canal, which are
      transported to the gut by the muscular sucking pump in the head. The dual
      functionality of the proboscis represents a key innovation for exploiting a vast
      range of nutritional sources. We suggest that future studies of the adaptive
      radiation of the Lepidoptera take into account the role played by the structural
      organization of the proboscis. A transformative two-step model of capillary
      intake and suctioning can be applied not only to butterflies and moths but also
      potentially to vast numbers of other insects such as bees and flies.

PMID- 21849383
TI  - Bone-titanium oxide interface in humans revealed by transmission electron
      microscopy and electron tomography.
AB  - Osseointegration, the direct contact between an implant surface and bone tissue,
      plays a critical role in interfacial stability and implant success. Analysis of
      interfacial zones at the micro- and nano-levels is essential to determine the
      extent of osseointegration. In this paper, a series of state-of-the-art
      microscopy techniques are used on laser-modified implants retrieved from humans.
      Partially laser-modified implants were retrieved after two and a half months'
      healing and processed for light and electron microscopy. Light microscopy showed
      osseointegration, with bone tissue growing both towards and away from the implant
      surface. Transmission electron microscopy revealed an intimate contact between
      mineralized bone and the laser-modified surface, including bone growth into the
      nano-structured oxide. This novel observation was verified by three-dimensional Z
      contrast electron tomography, enabling visualization of an apatite layer, with
      different crystal direction compared with the apatite in the bone tissue,
      encompassing the nano-structured oxide. In conclusion, the present study
      demonstrates the nano-scale osseointegration and bonding between apatite and
      surface-textured titanium oxide. These observations provide novel data in human
      specimens on the ultrastructure of the titanium-bone interface.

PMID- 21849384
TI  - Resistance and relatedness on an evolutionary graph.
AB  - When investigating evolution in structured populations, it is often convenient to
      consider the population as an evolutionary graph-individuals as nodes, and whom
      they may act with as edges. There has, in recent years, been a surge of interest
      in evolutionary graphs, especially in the study of the evolution of social
      behaviours. An inclusive fitness framework is best suited for this type of study.
      A central requirement for an inclusive fitness analysis is an expression for the
      genetic similarity between individuals residing on the graph. This has been a
      major hindrance for work in this area as highly technical mathematics are often
      required. Here, I derive a result that links genetic relatedness between haploid
      individuals on an evolutionary graph to the resistance between vertices on a
      corresponding electrical network. An example that demonstrates the potential
      computational advantage of this result over contemporary approaches is provided.
      This result offers more, however, to the study of population genetics than
      strictly computationally efficient methods. By establishing a link between gene
      transfer and electric circuit theory, conceptualizations of the latter can
      enhance understanding of the former.

PMID- 21849385
TI  - Insights into mucosal innate responses to Escherichia coli O157 : H7 colonization
      of cattle by mathematical modelling of excretion dynamics.
AB  - Mathematical model-based statistical inference applied to within-host dynamics of
      infectious diseases can help dissect complex interactions between hosts and
      microbes. This work has applied advances in model-based inference to understand
      colonization of cattle by enterohaemorrhagic Escherichia coli O157 : H7 at the
      terminal rectum. A mathematical model was developed based on niche replication
      and transition rates at this site. A nested-model comparison, applied to
      excretion curves from 25 calves, was used to reduce complexity while maintaining
      integrity. We conclude that, 5-9 days post inoculation, the innate immune
      response negates bacterial replication on the epithelium and either reduces
      attachment to or increases detachment from the epithelium of the terminal rectum.
      Thus, we provide a broadly applicable model that gives novel insights into
      bacterial replication rates in vivo and the timing and impact of host responses.

PMID- 21849386
TI  - Morphogenesis of an extended phenotype: four-dimensional ant nest architecture.
AB  - Animals produce a variety of structures to modify their environments adaptively.
      Such structures represent extended phenotypes whose development is rarely
      studied. To begin to rectify this, we used micro-computed tomography (CT)
      scanning and time-series experiments to obtain the first high-resolution dataset
      on the four-dimensional growth of ant nests. We show that extrinsic features
      within the environment, such as the presence of planes between layers of
      sediment, influence the architecture of Lasius flavus nests, with ants excavating
      horizontal tunnels along such planes. Intrinsically, the dimensions of the
      tunnels are associated with individual colonies, the dynamics of excavation can
      be explained by negative feedback and the angular distribution of tunnels is
      probably a result of local competition among tunnels for miners. The architecture
      and dynamics of ant nest excavation therefore result from local interactions of
      ants with one another and templates inherent in the environment. The influence of
      the environment on the form of structures has been documented across both biotic
      and abiotic domains. Our study opens up the utility of CT scanning as a technique
      for observing the morphogenesis of such structures.

PMID- 21849387
TI  - An equilibrium for phenotypic variance in fluctuating environments owing to
      epigenetics.
AB  - The connection between random environments and genetic and phenotypic variability
      has been a major focus in the population genetic literature. By providing
      differential access to the underlying genetic information, epigenetic variation
      could play an important role in the interaction between environmental and
      phenotypic variation. Using simulation, we model epigenetic plasticity during
      development by investigating the dynamics of genetic regulators of the epigenetic
      machinery that change the variance of the phenotype, while having no effect on
      the phenotype's mean. Previous studies have found that increased phenotypic
      variance is selected for if the environment is fluctuating. Here, we find that
      when a variance-increasing allele achieves a sufficiently high frequency, it can
      be out-competed by a variance-reducing allele, with the consequence that the
      population evolves to an equilibrium phenotypic variability. This equilibrium is
      shown to be robust to different initial conditions, but to depend heavily on
      parameters of the model, such as the mutation rate, the fitness landscape and the
      nature of the environmental fluctuation. Indeed, if there is no mutation at the
      genes controlling the variance of the phenotype, reduction of this variance is
      favoured.

PMID- 21849389
TI  - Modelling the dynamics of viral suppressors of RNA silencing.
AB  - Virus infection in plants is limited by RNA silencing. In turn, viruses can
      counter RNA silencing with silencing suppressors. Viral suppressors of RNA
      silencing have been shown to play a role in symptom development in plants. We
      here study four different strategies employed by silencing suppressors: small
      interfering RNA (siRNA) binding, double-strand RNA (dsRNA) binding and degrading
      or inactivating Argonaute. We study the effect of the suppressors on viral
      accumulation within the cell as well as its spread on a tissue with mathematical
      and computational models. We find that suppressors which target Argonaute are
      very effective in a single cell, but that targeting dsRNA or siRNA is much more
      effective at the tissue level. Although targeting Argonaute can be beneficial for
      viral spread, it can also cause hindrance in some cases owing to raised levels of
      siRNAs that can spread to other cells.

PMID- 21849388
TI  - Estimation of gestational age from fundal height: a solution for resource-poor
      settings.
AB  - Many women in resource-poor settings lack access to reliable gestational age
      assessment because they do not know their last menstrual period; there is no
      ultrasound (US) and methods of newborn gestational age dating are not practised
      by birth attendants. A bespoke multiple-measures model was developed to predict
      the expected date of delivery determined by US. The results are compared with
      both a linear and a nonlinear model. Prospectively collected early US and serial
      symphysis-pubis fundal height (SFH) data were used in the models. The data were
      collected from Karen and Burmese women attending antenatal care on the Thai
      Burmese border. The multiple-measures model performed best, resulting in a range
      of accuracy depending on the number of SFH measures recorded per mother (for
      example six SFH measurements resulted in a prediction accuracy of +/-2 weeks).
      SFH remains the proxy for gestational age in much of the resource-poor world.
      While more accurate measures should be encouraged, we demonstrate that a formula
      that incorporates at least three SFH measures from an individual mother and the
      slopes between them provide a significant increase in the accuracy of prediction
      compared with the linear and nonlinear formulae also using multiple SFH measures.

PMID- 21849390
TI  - Computability, Godel's incompleteness theorem, and an inherent limit on the
      predictability of evolution.
AB  - The process of evolutionary diversification unfolds in a vast genotypic space of
      potential outcomes. During the past century, there have been remarkable advances
      in the development of theory for this diversification, and the theory's success
      rests, in part, on the scope of its applicability. A great deal of this theory
      focuses on a relatively small subset of the space of potential genotypes, chosen
      largely based on historical or contemporary patterns, and then predicts the
      evolutionary dynamics within this pre-defined set. To what extent can such an
      approach be pushed to a broader perspective that accounts for the potential open
      endedness of evolutionary diversification? There have been a number of
      significant theoretical developments along these lines but the question of how
      far such theory can be pushed has not been addressed. Here a theorem is proven
      demonstrating that, because of the digital nature of inheritance, there are
      inherent limits on the kinds of questions that can be answered using such an
      approach. In particular, even in extremely simple evolutionary systems, a
      complete theory accounting for the potential open-endedness of evolution is
      unattainable unless evolution is progressive. The theorem is closely related to
      Godel's incompleteness theorem, and to the halting problem from computability
      theory.

PMID- 21849391
TI  - It's time for the UK government to fully review drug policy.

PMID- 21849392
TI  - Russia's alcohol problem.

PMID- 21849393
TI  - Disability assessment doctors come under GMC scrutiny.

PMID- 21849394
TI  - Robust synthetic gene network design via library-based search method.
AB  - MOTIVATION: Synthetic biology aims to develop the artificial gene networks with
      desirable behaviors using systematic method. These networks with desired
      behaviors could be constructed using diverse biological parts, which may limit
      the development to complex synthetic gene networks. Fortunately, some well
      characterized promoter libraries for engineering gene networks are widely
      available. Thus, a synthetic gene network can be constructed by selecting
      adequate promoters from promoter libraries to achieve the desired behaviors.
      However, the present promoter libraries cannot be directly applied to engineer a
      synthetic gene network. In order to efficiently select adequate promoters from
      promoter libraries for a synthetic gene network, promoter libraries are needed to
      be redefined based on the dynamic gene regulation. RESULTS: Based on four design
      specifications, a library-based search method is proposed to efficiently select
      the most adequate promoter set from the redefined promoter libraries by a genetic
      algorithm (GA) to achieve optimal reference tracking design. As the number and
      size of promoter libraries increase, the proposed method can play an important
      role in the systematic design of synthetic biology. CONTACT:
      g883743@alumni.nthu.edu.tw; bschen@ee.nthu.edu.tw SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 21849395
TI  - Simultaneous recognition and segmentation of cells: application in C.elegans.
AB  - MOTIVATION: Automatic recognition of cell identities is critical for quantitative
      measurement, targeting and manipulation of cells of model animals at single-cell
      resolution. It has been shown to be a powerful tool for studying gene expression
      and regulation, cell lineages and cell fates. Existing methods first segment
      cells, before applying a recognition algorithm in the second step. As a result,
      the segmentation errors in the first step directly affect and complicate the
      subsequent cell recognition step. Moreover, in new experimental settings, some of
      the image features that have been previously relied upon to recognize cells may
      not be easy to reproduce, due to limitations on the number of color channels
      available for fluorescent imaging or to the cost of building transgenic animals.
      An approach that is more accurate and relies on only a single signal channel is
      clearly desirable. RESULTS: We have developed a new method, called simultaneous
      recognition and segmentation (SRS) of cells, and applied it to 3D image stacks of
      the model organism Caenorhabditis elegans. Given a 3D image stack of the animal
      and a 3D atlas of target cells, SRS is effectively an atlas-guided voxel
      classification process: cell recognition is realized by smoothly deforming the
      atlas to best fit the image, where the segmentation is obtained naturally via
      classification of all image voxels. The method achieved a 97.7% overall
      recognition accuracy in recognizing a key class of marker cells, the body wall
      muscle (BWM) cells, on a dataset of 175 C.elegans image stacks containing 14 118
      manually curated BWM cells providing the 'ground-truth' for accuracy. This result
      was achieved without any additional fiducial image features. SRS also
      automatically identified 14 of the image stacks as involving +/-90 degrees 
      rotations. With these stacks excluded from the dataset, the recognition accuracy
      rose to 99.1%. We also show SRS is generally applicable to other cell types, e.g.
      intestinal cells. AVAILABILITY: The supplementary movies can be downloaded from
      our web site http://penglab.janelia.org/proj/celegans_seganno. The method has
      been implemented as a plug-in program within the V3D system
      (http://penglab.janelia.org/proj/v3d), and will be released in the V3D plugin
      source code repository. CONTACT: pengh@janelia.hhmi.org.

PMID- 21849396
TI  - Seed traits and genes important for translational biology--highlights from recent
      discoveries.
AB  - Seeds provide food, feed, fiber and fuel. They are also an important delivery
      system of genetic information, which is essential for the survival of wild
      species in ecosystems and the production of agricultural crops. In this review,
      seed traits and genes that are potentially important for agricultural
      applications are discussed. Over the long period of crop domestication, seed
      traits have been modified through intentional or unintentional selections. While
      most selections have led to seed traits favorable for agricultural consumption,
      such as larger seeds with higher nutritional value than the wild type, other
      manipulations in modern breeding sometimes led to negative traits, such as
      vivipary, precocious germination on the maternal plant or reduced seed vigor, as
      a side effect during the improvement of other characteristics. Greater effort is
      needed to overcome these problems that have emerged as a consequence of crop
      improvement. Seed biology researchers have characterized the function of many
      genes in the last decade, including those associated with seed domestication,
      which may be useful in addressing critical issues in modern agriculture, such as
      the prevention of vivipary and seed shattering or the enhancement of yields.
      Recent discoveries in seed biology research are highlighted in this review, with
      an emphasis on their potential for translational biology.

PMID- 21849397
TI  - Arabidopsis CYP94B3 encodes jasmonyl-L-isoleucine 12-hydroxylase, a key enzyme in
      the oxidative catabolism of jasmonate.
AB  - The hormonal action of jasmonate in plants is controlled by the precise balance
      between its biosynthesis and catabolism. It has been shown that jasmonyl-L
      isoleucine (JA-Ile) is the bioactive form involved in the jasmonate-mediated
      signaling pathway. However, the catabolism of JA-Ile is poorly understood.
      Although a metabolite, 12-hydroxyJA-Ile, has been characterized, detailed
      functional studies of the compound and the enzyme that produces it have not been
      conducted. In this report, the kinetics of wound-induced accumulation of 12
      hydroxyJA-Ile in plants were examined, and its involvement in the plant wound
      response is described. Candidate genes for the catabolic enzyme were narrowed
      down from 272 Arabidopsis Cyt P450 genes using Arabidopsis mutants. The candidate
      gene was functionally expressed in Pichia pastoris to reveal that CYP94B3 encodes
      JA-Ile 12-hydroxylase. Expression analyses demonstrate that expression of CYP94B3
      is induced by wounding and shows specific activity toward JA-Ile. Plants grown in
      medium containing JA-Ile show higher sensitivity to JA-Ile in cyp94b3 mutants
      than in wild-type plants. These results demonstrate that CYP94B3 plays a major
      regulatory role in controlling the level of JA-Ile in plants.

PMID- 21849398
TI  - Effects of image characteristics on performance of tumor delineation methods: a
      test-retest assessment.
AB  - PET can be used to monitor response during chemotherapy and assess biologic
      target volumes for radiotherapy. Previous simulation studies have shown that the
      performance of various automatic or semiautomatic tumor delineation methods
      depends on image characteristics. The purpose of this study was to assess test
      retest variability of tumor delineation methods, with emphasis on the effects of
      several image characteristics (e.g., resolution and contrast). METHODS: Baseline
      test-retest data from 19 non-small cell lung cancer patients were obtained using
      (18)F-FDG (n = 10) and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) (n = 9).
      Images were reconstructed with varying spatial resolution and contrast. Six
      different types of tumor delineation methods, based on various thresholds or on a
      gradient, were applied to all datasets. Test-retest variability of metabolic
      volume and standardized uptake value (SUV) was determined. RESULTS: For both
      tracers, size of metabolic volume and test-retest variability of both metabolic
      volume and SUV were affected by the image characteristics and tumor delineation
      method used. The median volume test-retest variability ranged from 8.3% to 23%
      and from 7.4% to 29% for (18)F-FDG and (18)F-FLT, respectively. For all image
      characteristics studied, larger differences (<=10-fold higher) were seen in test
      retest variability of metabolic volume than in SUV. CONCLUSION: Test-retest
      variability of both metabolic volume and SUV varied with tumor delineation
      method, radiotracer, and image characteristics. The results indicate that a
      careful optimization of imaging and delineation method parameters is needed when
      metabolic volume is used, for example, as a response assessment parameter.

PMID- 21849399
TI  - Coronary circulatory function in patients with the metabolic syndrome.
AB  - The metabolic syndrome affects 25% of the U.S. population and greatly increases
      the risk of diabetes and coronary artery disease (CAD). We tested the hypothesis
      that the metabolic syndrome is associated with impaired coronary vasodilator
      function, a marker of atherosclerotic disease activity. METHODS: Four hundred
      sixty-two patients at risk for CAD, as defined by a low-density lipoprotein
      cholesterol >= 160 mg/dL with fewer than 2 coronary risk factors, a low-density
      lipoprotein cholesterol >= 130 mg/dL with 2 or more coronary risk factors, or
      with documented CAD were included. A subset of 234 individuals underwent repeated
      PET at 1 y. Myocardial blood flow (MBF) and vasodilator reserve were assessed by
      PET. Modified criteria of the National Cholesterol Education Program, Adult
      Treatment Panel III were used to characterize the metabolic syndrome. RESULTS:
      Adenosine- and cold-stimulated MBF were similar in patients with and without
      metabolic syndrome, whereas baseline MBF showed a stepwise increase with
      increasing features of the syndrome. Consequently, patients with metabolic
      syndrome showed a lower coronary flow reserve (CFR) (2.5 +/- 1.0) than those
      without metabolic syndrome (3.0 +/- 0.9, P = 0.004). Differences in CFR were no
      longer present after correcting rest flows for the rate-pressure product. Change
      in MBF and CFR at 1 y were not different across groups of patients with
      increasing features of the metabolic syndrome. CONCLUSION: Patients with
      metabolic syndrome demonstrate impaired CFR, which is related to the augmentation
      in resting coronary blood flow caused by hypertension. In high-risk individuals,
      peak adenosine- and cold-stimulated blood flows are impaired even in the absence
      of the metabolic syndrome.

PMID- 21849400
TI  - The usefulness of a preoperative compact imager, a hand-held gamma-camera for
      breast cancer sentinel node biopsy: final results of a prospective double-blind,
      clinical study.
AB  - The aim of this study was to compare the effectiveness of a hand-held
      preoperative compact imager (POCI) camera with conventional lymphoscintigraphy
      using a gamma-camera for sentinel lymph node (SLN) detection in breast cancer.
      METHODS: The main objective was to demonstrate the noninferiority of the POCI
      relative to conventional lymphoscintigraphy and to compare the number of SLNs
      detected by the 2 imaging devices. Our study, a clinical prospective, double
      blind, noninferiority study, planned to include 200 patients with early breast
      cancer and started in January 2006. A standard SLN protocol (4 periareolar
      injections of 37 MBq of (99m)Tc-nanocolloids, 2 h before lymphoscintigraphy) was
      performed preoperatively using a conventional gamma-camera and then the POCI
      camera. Scans were obtained by 2 different nuclear medicine physicians unaware of
      each other's results. The day after, in the operating room, the surgeon, after
      receiving the previous results, used the counting probe for surgical SLN biopsy.
      The number and localization of axillary SLNs obtained by lymphoscintigraphy and
      the POCI and the duration of the whole procedure were determined. RESULTS: Among
      the 162 patients included, 138 were evaluable. The POCI detected more SLNs than
      did lymphoscintigraphy in 50 patients (36%), the same number of in 54 patients
      (39%), and fewer SLNs in 34 patients (25%), representing 84 (61%) discordant
      pairs. The noninferiority of preoperative compact imaging of axillary SLNs
      numbers was found to be statistically significant (95% confidence interval, 30%
      52%, P = 0.025) using the McNemar test. The duration of acquisition was shorter
      using the POCI (<10 min in 84% [n = 117] of patients; mean, 7.5 +/- 3.3 min) than
      lymphoscintigraphy (13% [n = 18] of patients; mean, 15.7 +/- 3.4 min), with P <
      0.001 using the McNemar test for paired proportions. CONCLUSION: Preoperative
      compact imaging using a hand-held camera was able to predict the number and
      localization of breast cancer SLNs and was not inferior to conventional
      lymphoscintigraphy in this study. Further studies will determine whether
      preoperative compact imaging could replace lymphoscintigraphy, especially in
      surgical centers without an on-site nuclear medicine department.

PMID- 21849401
TI  - Radiolabeled fucoidan as a p-selectin targeting agent for in vivo imaging of
      platelet-rich thrombus and endothelial activation.
AB  - P-selectin expression is involved in the pathophysiology of biologically active
      arterial thrombus and endothelial activation after a transient ischemic event.
      Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. In
      the present study, we propose a new approach of P-selectin molecular imaging
      based on radiolabeled fucoidan. METHODS: Two kinds of experimental models were
      selected to evaluate the ability of radiolabeled fucoidan to detect P-selectin
      expression: platelet-rich arterial thrombi (vegetations of infective endocarditis
      and arterial mural thrombus) and myocardial ischemia-reperfusion. These 2
      settings were chosen because they were clinically relevant, and both were
      associated with an important overexpression of platelet and endothelial P
      selectin, respectively. RESULTS: (99m)Tc-fucoidan SPECT was able to detect the
      presence of platelet-rich arterial thrombi in all animals, with a median target
      to-background ratio of 5.2 in vegetations of endocarditis and 3.6 in mural
      aneurysmal thrombus, and to detect a persistent endothelial activation at 2 h
      after reperfusion. In this latter model, the magnitude of the signal was
      correlated with the extent of myocardium that underwent transient ischemia. The
      sensitivity of selectivity of the uptake and retention of (99m)Tc-fucoidan in
      both settings was excellent. CONCLUSION: This study supports (99m)Tc-fucoidan as
      a relevant imaging agent for in vivo detection of biologic activities associated
      with P-selectin overexpression, such as arterial thrombus and ischemic memory.
      Given the reported wide availability at a low cost, and its low toxicity,
      fucoidan seems to overcome some of the limitations of previous P-selectin
      targeted imaging agents.

PMID- 21849402
TI  - Phase I, first-in-human study of BMS747158, a novel 18F-labeled tracer for
      myocardial perfusion PET: dosimetry, biodistribution, safety, and imaging
      characteristics after a single injection at rest.
AB  - (18)F-labeled BMS747158 is a novel myocardial perfusion imaging tracer that
      targets mitochondrial complex 1. The objectives of this phase I study were to
      evaluate radiation dosimetry, biodistribution, human safety, tolerability, and
      early elimination of (18)F activity in urine after injection of a single dose of
      the tracer at rest in healthy subjects. METHODS: Thirteen healthy subjects were
      injected with 170-244 MBq (4.6-6.6 mCi) of BMS747158 intravenously. Dynamic PET
      was obtained over the heart for 10 min, followed by sequential whole-body imaging
      for 5 h. Blood samples and urinary excretion were collected for up to 8 h. Heart
      rate, electrocardiogram, and blood pressure were monitored before and during
      imaging. The residence times were determined from multiexponential regression of
      organ region-of-interest data normalized by injected dose. Absorbed dose
      estimates for all target organs were determined using MIRD schema with OLINDA/EXM
      software. RESULTS: The organ receiving the largest mean absorbed dose was the
      kidneys at 0.066 mSv/MBq (0.24 rem/mCi), followed by the heart wall at 0.048
      mSv/MBq (0.18 rem/mCi). The mean effective dose was 0.019 mSv/MBq (0.072
      rem/mCi). The heart exhibited high and sustained retention of BMS747158 from the
      earliest images through approximately 5 h after injection. There were no drug
      related adverse events, and the tracer was well tolerated in all subjects. Mean
      urinary excretion was 4.83 percentage injected dose (range, 0.64-12.41 percentage
      injected dose). CONCLUSION: These preliminary data suggest that (18)F-labeled
      BMS747158 appears to be well tolerated and has a unique potential for myocardial
      perfusion PET.

PMID- 21849403
TI  - Using the NEMA NU 4 PET image quality phantom in multipinhole small-animal SPECT.
AB  - Several commercial small-animal SPECT scanners using multipinhole collimation are
      presently available. However, generally accepted standards to characterize the
      performance of these scanners do not exist. Whereas for small-animal PET, the
      National Electrical Manufacturers Association (NEMA) NU 4 standards have been
      defined in 2008, such standards are still lacking for small-animal SPECT. In this
      study, the image quality parameters associated with the NEMA NU 4 image quality
      phantom were determined for a small-animal multipinhole SPECT scanner. METHODS:
      Multiple whole-body scans of the NEMA NU 4 image quality phantom of 1-h duration
      were performed in a U-SPECT-II scanner using (99m)Tc with activities ranging
      between 8.4 and 78.2 MBq. The collimator contained 75 pinholes of 1.0-mm diameter
      and had a bore diameter of 98 mm. Image quality parameters were determined as a
      function of average phantom activity, number of iterations, postreconstruction
      spatial filter, and scatter correction. In addition, a mouse was injected with
      (99m)Tc-hydroxymethylene diphosphonate and was euthanized 6.5 h after injection.
      Multiple whole-body scans of this mouse of 1-h duration were acquired for
      activities ranging between 3.29 and 52.7 MBq. RESULTS: An increase in the number
      of iterations was accompanied by an increase in the recovery coefficients for the
      small rods (RC(rod)), an increase in the noise in the uniform phantom region, and
      a decrease in spillover ratios for the cold-air- and water-filled scatter
      compartments (SOR(air) and SOR(wat)). Application of spatial filtering reduced
      image noise but lowered RC(rod). Filtering did not influence SOR(air) and
      SOR(wat). Scatter correction reduced SOR(air) and SOR(wat). The effect of total
      phantom activity was primarily seen in a reduction of image noise with increasing
      activity. RC(rod), SOR(air), and SOR(wat) were more or less constant as a
      function of phantom activity. The relation between acquisition and reconstruction
      settings and image quality was confirmed in the (99m)Tc-hydroxymethylene
      diphosphonate mouse scans. CONCLUSION: Although developed for small-animal PET,
      the NEMA NU 4 image quality phantom was found to be useful for small-animal SPECT
      as well, allowing for objective determination of image quality parameters and
      showing the trade-offs between several of these parameters on variation of
      acquisition and reconstruction settings.

PMID- 21849405
TI  - Hyperpolarized 13C MRI and PET: in vivo tumor biochemistry.
AB  - Dynamic nuclear polarization (DNP) is an emerging technique for dramatically
      increasing the sensitivity of magnetic resonance spectroscopy (MRS). This review
      evaluates the potential strengths and weaknesses of DNP-enhanced (13)C magnetic
      resonance spectroscopic imaging (DNP-MRSI) as a clinical imaging technique in
      comparison to PET. The major advantage of MRS is chemical shift, which enables
      the injected molecule to be observed separately from its metabolites, whereas the
      major advantage of PET is its high sensitivity. Factors such as spatial and
      temporal resolution and potential risks and costs of the two techniques will be
      discussed. PET tracers and (13)C-labeled molecules that can be used in oncology
      will be reviewed with reference to the biologic processes they detect. Because
      DNP-MRSI and PET are, in principle, similar techniques for assessing tumor
      metabolism, the experiences gained during the development of PET may help to
      accelerate translation of DNP-MRSI into routine patient imaging.

PMID- 21849404
TI  - Human dosimetry and preliminary tumor distribution of 18F-fluoropaclitaxel in
      healthy volunteers and newly diagnosed breast cancer patients using PET/CT.
AB  - (18)F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used
      chemotherapy agent. Preclinical data suggest that (18)F-fluoropaclitaxel may be a
      reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P
      glycoprotein, a drug efflux pump associated with multidrug resistance, (18)F
      fluoropaclitaxel may also be useful in identifying multidrug resistance and
      predicting tumor response for drugs other than paclitaxel. METHODS: After
      informed consent was obtained, 3 healthy volunteers and 3 patients with untreated
      breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received
      an intravenous infusion of (18)F-fluoropaclitaxel and then underwent PET/CT.
      Healthy volunteers underwent serial whole-body imaging over an approximately 3-h
      interval, and organ (18)F residence times were determined from the time-activity
      curves uncorrected for decay to determine dosimetry. Radiation dose estimates
      were calculated using OLINDA/EXM software. For breast cancer patients, dynamic
      imaging of the primary tumor was performed for 60 min, followed by static whole
      body scans at 1 and 2 h after injection. RESULTS: Dosimetry calculations showed
      that the gallbladder received the highest dose (229.50 MUGy/MBq [0.849 rad/mCi]),
      followed by the small and large intestines (161.26 MUGy/MBq [0.597 rad/mCi] and
      184.59 MUGy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 MUGy/MBq
      (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the
      decay-corrected activity was in the gastrointestinal system, with a mean of 0.01%
      in the tumor. All 3 breast cancer patients showed retention of (18)F
      fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no
      invasive cancer in the breast or axillary nodes) to chemotherapy that included a
      taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to
      background ratio increased with time to a maximum of 7.7 at 20 min. CONCLUSION:
      This study demonstrates the feasibility of using (18)F-fluoropaclitaxel PET/CT
      tumor imaging and provides radiation dosimetry measurements in humans. Although
      further study is needed, it is hoped that the measured intratumoral (18)F
      fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and
      potentially other chemotherapeutic agent retention, in solid tumors.

PMID- 21849406
TI  - 99mTc-Hydrazinonicotinamide epidermal growth factor-polyethylene glycol-quantum
      dot imaging allows quantification of breast cancer epidermal growth factor
      receptor expression and monitors receptor downregulation in response to cetuximab
      therapy.
AB  - Therapy of cancer, including basallike breast tumors, that targets the epidermal
      growth factor receptor (EGFR) would greatly benefit from noninvasive methods that
      can quantitatively monitor receptor status and treatment response. METHODS: Here,
      we investigated the potential of a novel technique based on streptavidin cadmium
      selenide/zinc sulfide quantum dots (Qdots) multiplexed with polyethylene glycol
      (PEG), epidermal growth factor (EGF), and (99m)Tc-hydrazinonicotinamide. In vitro
      binding affinity and specificity were evaluated in cultured cells.
      Biodistribution studies and in vivo imaging were performed in murine breast tumor
      xenografts of basallike phenotype MDA-MB-468 cells and EGFR-negative cells.
      RESULTS: (99m)Tc-hydrazinonicotinamide EGF-PEG-Qdot showed specific and high
      affinity EGFR targeting on confocal microscopy, immunoblotting, and binding
      assays. When intravenously injected, MDA-MB-468 tumors were visualized with high
      contrast by both optical and scintigraphic imaging. Scintigraphic image-based
      quantification correctly discriminated high-EGFR-expressing MDA-MB-468 tumors
      from other tumors, and image-based tumor uptake closely correlated to EGFR
      content. Importantly, serial imaging of MDA-MB-468 tumors responding to cetuximab
      therapy could detect a significant reduction of tumor uptake that was paralleled
      by downregulation of EGFR expression. Furthermore, high baseline uptake predicted
      good response to cetuximab therapy. CONCLUSION: (99m)Tc-hydrazinonicotinamide EGF
      PEG-Qdot provides EGFR-targeted imaging of breast tumors and may allow
      noninvasive monitoring of EGFR status in living subjects before and after
      targeted therapies.

PMID- 21849407
TI  - Phospholemman-dependent regulation of the cardiac Na/K-ATPase activity is
      modulated by inhibitor-1 sensitive type-1 phosphatase.
AB  - Cardiac Na/K-ATPase (NKA) is regulated by its accessory protein phospholemman
      (PLM). Whereas kinase-induced PLM phosphorylation has been shown to mediate NKA
      stimulation, the role of endogenous phosphatases is presently unknown. We
      investigated the role of protein phosphatase-1 (PP-1) on PLM phosphorylation and
      NKA activity in rat cardiomyocytes and failing human hearts. Incubation of rat
      cardiomyocytes with the chemical PP-1/PP-2A inhibitor okadaic acid or the
      specific PP-1-inhibitor peptide (I-1ct) identified PLM phosphorylation at Ser-68
      as the main substrate for PP-1. Moreover, myocytes adenovirally overexpressing PP
      1 inhibitor-1 protein (I-1,Ad-I-1/eGFP) showed a 70% increase in PLM Ser-68
      phosphorylation and 65% increase in NKA current, compared with enhanced green
      fluorescence protein (eGFP)-infected controls (Ad-eGFP), using Western blotting
      and voltage clamping, respectively. Notably, in left ventricular myocardium from
      patients with heart failure, PLM Ser-68 phosphorylation was ~ 50% lower (n=7)
      than in nonfailing controls (n=7). We provide the first physiological and
      biochemical evidence that PLM phosphorylation and cardiac Na/K-ATPase activity
      are negatively regulated by PP-1 and that this regulatory mechanism could be
      counteracted by I-1. This novel mechanism is markedly perturbed in failing hearts
      favoring PLM dephosphorylation and NKA deactivation and thus may contribute to
      maladaptive hypertrophy and arrhythmogenesis via chronically higher intracellular
      Na and Ca concentrations.

PMID- 21849408
TI  - What does it take to be a smoker? Adolescents' characterization of different
      smoker types.
AB  - INTRODUCTION: Studies have demonstrated that clinical- and research-based
      definitions of who a smoker is and what constitutes smoking often differ from
      adolescent-derived definitions, which can be problematic for effective
      intervention and prevention efforts. We investigated how adolescents define
      different smoker types (nonsmoker, smoker, regular smoker, addicted smoker, heavy
      smoker, experimental smoker, casual smoker, and social smoker) using multiple
      indicators of smoking behaviors, including frequency, amount, place, and length
      of time cigarette smoking, and whether differences exist by smoking experience.
      METHODS: Quantitative and qualitative methods were used to analyze data from a
      cohort of adolescents (N = 372) in northern California. RESULTS: We found
      differences in how adolescents characterized smoker types based on their own
      smoking experience. Ever-smokers tended to have a greater flexibility in
      determining what constituted nonsmoking and heavy smoking, while never-smokers
      had much narrower definitions. Results also indicated that adolescents may
      mistakenly associate nicotine addiction with a high frequency and amount of
      cigarette use as 74.3% characterized an addicted smoker as having smoked for a
      few years or more. In addition, there was a considerable amount of overlap in
      definitions between different smoker types, particularly among the smoker-regular
      smoker, addicted smoker-heavy smoker, and casual smoker-social smoker pairs.
      CONCLUSION: Health communication strategies for youth smoking prevention need to
      address the wide variability and overlap in how adolescents define different
      smoker types. Greater attention should be directed to understanding the nuances
      of how adolescents define smoking in order to maximize the effectiveness of youth
      centered smoking prevention and cessation messages.

PMID- 21849409
TI  - Impulsivity and symptoms of nicotine dependence in a young adult population.
AB  - INTRODUCTION: Impulsivity is widely regarded as a risk factor for drug
      dependence. However, its relationship with the symptomatology of nicotine
      dependence is poorly understood. METHODS: To examine the nature of these
      relationships, we recruited 404 daily and occasional smokers from a predominantly
      student population and assessed the association between impulsivity, as measured
      by the Barratt Impulsiveness Scale (BIS-11) and several self-reported measures of
      smoking rate and nicotine dependence, including the Diagnostic and Statistical
      Manual's (DSM-IV) criteria. RESULTS: Overall, impulsivity was high throughout the
      entire sample but only modestly associated with nicotine dependence. Within the
      diagnostic criteria of nicotine dependence, two symptoms, which reflect
      automatized or habitual smoking, were most strongly associated with impulsivity.
      CONCLUSION: These data support recent human and animal work, which suggests that
      impulsivity is linked to the formation of habitual drug use, and are discussed
      within the framework of a dual-system account of drug seeking.

PMID- 21849410
TI  - The Smoking-Related Weight and Eating Episodes Test (SWEET): development and
      preliminary validation.
AB  - INTRODUCTION: Many smokers believe that smoking helps them to control their
      weight, and concerns about weight gain can interfere with smoking cessation. As
      researchers typically assess general weight concerns, a measure specific to
      smoking-related weight concerns is needed. METHODS: The Smoking-related Weight
      and Eating Episodes Test (SWEET) was created by generating items from 4 content
      domains: Hunger, Craving, Overeating, and Body Image. Female undergraduate
      smokers (N = 280) rated their postcessation weight gain concern and completed the
      SWEET, Fagerstrom Test for Nicotine Dependence, Brief Smoking Consequences
      Questionnaire-Adult, Eating Attitudes Test (EAT)-26, Bulimia Test-Revised (BULIT
      R), and Body Shape Questionnaire. RESULTS: Factor analysis of the initial items
      suggested a 4-factor solution, suggesting 4 subscales: Smoking to suppress
      appetite, smoking to prevent overeating, smoking to cope with body
      dissatisfaction, and withdrawal-related appetite increases. Based on these
      results, the SWEET subscales were revised and shortened. The resulting 10-item
      SWEET showed excellent internal consistency (total alpha = .94; mean alpha = .86)
      and evidence of validity by predicting smoking frequency, eating pathology, and
      body image concerns (ps < .05). Smoking frequency, eating pathology, and body
      image concerns were significantly predicted by the SWEET while controlling for
      existing measures of postcessation weight gain concern. CONCLUSIONS: The SWEET
      appears to be a reliable and valid measure of tendencies to smoke in response to
      body image concern and nicotine withdrawal and as a way to control appetite and
      overeating.

PMID- 21849411
TI  - Cigarette smoking and serious psychological distress: a population-based study of
      California adults.
AB  - INTRODUCTION: This study examines differences in smoking behaviors between adults
      with and without serious psychological distress (SPD) in California, which has
      the longest running comprehensive tobacco control program in the world. METHODS:
      Cross-sectional data from the 2007 California Health Interview Survey on 50,880
      noninstitutionalized adults were used to analyze smoking prevalence, cigarette
      consumption, and quit ratio. Persons with SPD were identified using the K6 scale,
      a clinically validated psychological screening instrument. RESULTS: About 3.8% of
      California adults screened positive for SPD in the past 30 days (acute SPD) and
      an additional 4.8% screened positive for SPD in the past 2-12 months (recent
      SPD). Persons with SPD were more likely to be current smokers than those without
      SPD (adjusted odds ratios [AOR] = 2.54, 95% CI = 2.02-3.19 for acute SPD and AOR
      = 2.20, 95% CI = 1.79-2.71 for recent SPD). Current smokers with acute SPD were
      more likely to smoke >=20 cigarettes daily than those without SPD (AOR = 1.59,
      95% CI = 1.06-2.39). The quit rate was lower among ever-smokers with acute (AOR =
      0.46, 95% CI = 0.35-0.62) or recent SPD (AOR = 0.55, 95% CI = 0.42-0.71) than
      those without SPD. While persons with acute or recent SPD comprised 8.6% of
      adults, they consumed 19.2% of all cigarettes in California. CONCLUSIONS: In
      California, adults with SPD were more likely to be current smokers and to smoke
      heavily and less likely to quit than those without SPD. The findings underscore
      the need for effective smoking cessation strategies targeting this group.

PMID- 21849412
TI  - Tobacco as a social currency: cigarette gifting and sharing in China.
AB  - INTRODUCTION: China produces and consumes more tobacco than any other country in
      the world and as such is at the forefront of the world tobacco epidemic. Many
      studies have recently emerged that directly or indirectly reference the acts of
      giving and sharing cigarettes as a major contributor to China's high tobacco
      usage. The goal of this report is to review relevant literature relating to
      sharing and gifting cigarettes as well as provide useful historic and cultural
      contexts. Important differences between the act of giving individual cigarettes
      and the gifting of packaged cigarettes are explored as well as explanations for
      how both these practices have influenced current tobacco control efforts.
      METHODS: Available Chinese and English sources on gifting and sharing cigarettes
      in China published between 1991 and 2011 were reviewed and discussed with a
      cultural and historical background. RESULTS: The practices of gifting and sharing
      cigarettes strongly contribute to smoking initiation as well as failure to quit
      smoking among Chinese males. Historical and cultural roots have reinforced these
      practices and hampered efforts to reduce tobacco use in China. CONCLUSIONS:
      Traditional tobacco control efforts should be combined with culture-specific
      approaches to reduce tobacco usage in China. The regular exchange of cigarettes
      normalizes smoking across society and promotes tobacco's acceptability. Great
      efforts should be taken not only to minimize these practices among males but also
      to discourage their adoption by females.

PMID- 21849413
TI  - Hardcore smokers in Norway 1996-2009.
AB  - INTRODUCTION: The aim of this study was to investigate changes in the relative
      proportion of hardcore smokers (HCS) in Norway for the years 1996-2009. METHODS:
      Data were derived from Statistics Norway's annually cross-sectional
      representative samples of the adult population. The total sample size of smokers
      each year was between 250 and 500. The outcome measure was HCS, defined by their
      intention not to quit smoking and absence of attempts to quit during the last 12
      months. Logistic regression analysis was conducted to estimate the association
      between time (survey year) and the number of HCS. RESULTS: We identified three
      groups of smokers: occasional smokers, daily non-HCS, and HCS. The relative
      proportion of HCS declined in the period 1996-2009, from 30% to 23%. A model
      adjusted for gender, age, educational level, and the use of snus (smokeless
      tobacco) showed the same downward trend. CONCLUSIONS: Within this sample of
      Norwegian smokers, the relative share of HCS is not increasing. This knowledge is
      important for tobacco prevention policy. The result does not support a hardening
      hypothesis regarding changes in the size of the group of HCS. Further analysis is
      needed to investigate individual resistance to smoking cessation.

PMID- 21849414
TI  - Acute effects of aerobic exercise and Hatha yoga on craving to smoke.
AB  - INTRODUCTION: Recent studies have examined the effects of physical activity on
      craving to smoke and smoking withdrawal. The current study was designed to
      compare and contrast the effects of 2 different forms of physical activity on
      general and cue-elicited craving to smoke. METHODS: Following 1-hr nicotine
      abstinence, 76 daily smokers were randomly assigned to engage in a 30-min bout of
      cardiovascular exercise (CE; brisk walk on a treadmill), Hatha yoga (HY), or a
      nonactivity control condition. Participants completed measures of craving and
      mood, and a smoking cue reactivity assessment, before, immediately following, and
      approximately 20 min after the physical activity or control conditions. RESULTS:
      Compared with the control condition, participants in each of the physical
      activity groups reported a decrease in craving to smoke, an increase in positive
      affect, and a decrease in negative affect. In addition, craving in response to
      smoking cues was specifically reduced among those who engaged in CE, whereas
      those who engaged in HY reported a general decrease in cravings. CONCLUSIONS:
      This study provides further support for the use of exercise bouts for attenuating
      cigarette cravings during temporary nicotine abstinence. Results also suggest
      that CE can attenuate cravings in response to smoking cues. There are several
      areas for further research that may improve integration of exercise within
      smoking cessation treatment.

PMID- 21849415
TI  - Single-dose pharmacokinetics of nicotine when given with a novel mouth spray for
      nicotine replacement therapy.
AB  - INTRODUCTION: As the efficacy of nicotine replacement therapy might be improved
      by faster systemic nicotine uptake, a new nicotine mouth spray has been
      developed. The current study was performed to evaluate the single-dose
      pharmacokinetics of nicotine at 3 doses of the mouth spray and to compare the
      speed of nicotine uptake from the spray versus nicotine lozenge and gum. METHODS:
      In a randomized crossover study, 45 healthy adult smokers received single doses
      of nicotine mouth spray 1, 2, and 4 mg, nicotine lozenge 4 mg, and nicotine gum 4
      mg on separate occasions. Blood samples were collected for 12 hr to determine
      pharmacokinetic variables. RESULTS: Mean plasma nicotine concentrations during
      the first 10 min, measured using area under the curve (AUC(10 min)), were 3 times
      as high with spray 4 mg as with lozenge or gum. The AUC(10 min) with 2 and 1 mg
      doses of spray, respectively, was twice and 1.5 times as high as the AUC(10 min)
      with lozenge or gum. The maximum baseline-corrected plasma nicotine concentration
      (cC(max)) with 4 mg spray exceeded that for lozenge and gum by 34% and 20%; the
      median time to reach C(max) was 10-12.5 min for the 3 doses of spray, 45 min for
      lozenge, and 30 min for gum. The mean baseline-corrected area under the plasma
      nicotine concentration-versus-time curve (cAUC(infinity)) with 4 mg spray was 15%
      higher than that with gum but did not differ significantly from that with
      lozenge. CONCLUSION: Nicotine delivered via the mouth spray is absorbed
      considerably faster than nicotine given via gum or lozenge.

PMID- 21849416
TI  - GSTM1 modifies the effect of maternal exposure to environmental tobacco smoke on
      neonatal primitive reflexes.
AB  - OBJECTIVE: The aim of this study was to examine whether infant metabolic gene
      polymorphisms modify the effect of maternal environmental tobacco smoke (ETS) on
      neonatal neurobehavior. METHODS: We conducted a birth cohort study of 87
      nonsmoking women who delivered single births of normal birth weight. We enrolled
      the women before delivery, interviewed them using a structured questionnaire, and
      collected umbilical cord blood. Umbilical cord cotinine, a blood indicator of
      prenatal ETS exposure, was analyzed. The Neonatal Neurobehavioral Examination
      Chinese Version (NNE-C) was administrated within 5 days after delivery to examine
      neonatal neurobehavior. Four infant metabolic genes, CYP1A1 MspI, CYP1A1
      Ile462Val, GSTT1, and GSTM1, were identified. RESULTS: Maternal ETS exposure
      during pregnancy was not related to neonatal neurobehavior when infant genetic
      polymorphisms were not considered. However, maternal ETS exposure did cause
      adverse effects in neonates with the absent type of GSTM1. Adverse effects were
      seen on the total NNE-C (beta = -2.55; p = .02) and on primitive reflexes (beta =
      -1.70; p = .004), especially in grasp reflexes (beta = -.36; p = .011) and tonic
      neck reflexes (beta = -.36; p = .049). In addition, there was a significant
      interaction between maternal ETS exposure and infant GSTM1 genotype on neonate
      grasp reflexes (p for interaction = .019). CONCLUSIONS: These data indicate that
      weaker responses in neonatal primitive reflexes in infants with the absent type
      GSTM1 were related to maternal ETS exposure during pregnancy.

PMID- 21849417
TI  - Identification of Epstein-Barr virus-induced gene 3 as a novel serum and tissue
      biomarker and a therapeutic target for lung cancer.
AB  - PURPOSE: This study aims to identify novel biomarkers and therapeutic targets for
      lung cancer. EXPERIMENTAL DESIGN: We carried out gene expression profile analysis
      of 120 lung cancers to screen for genes encoding transmembrane/secretory
      molecules that are commonly transactivated in lung cancers. Epstein-Barr virus
      induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a
      good candidate. Immunohistochemical staining using tissue microarray consisting
      of 414 non-small cell lung cancers was applied to examine the expression level
      and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training
      assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals
      for validation analysis (132 lung cancers and 41 healthy volunteers) were
      measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA
      and cell growth assays, using cells stably expressing exogenous EBI3. RESULTS:
      Immunohistochemical staining of EBI3 using tissue microarrays revealed that a
      high level of EBI3 expression was associated with a poor prognosis of lung cancer
      (P = 0.0014) and multivariate analysis confirmed it to be an independent
      prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were
      found to be significantly higher in lung cancer patients than in healthy
      volunteers; this result was also observed in the validation set. Furthermore,
      reduction in EBI3 expression by siRNA suppressed cancer cell proliferation
      whereas induction of exogenous EBI3 conferred growth-promoting activity.
      CONCLUSIONS: EBI3 is a potential serum and tissue biomarker as well as
      therapeutic target for lung cancer.

PMID- 21849418
TI  - BAD phosphorylation determines ovarian cancer chemosensitivity and patient
      survival.
AB  - PURPOSE: Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA)
      often develop drug resistance, which limits patient survival. Using specimens
      and/or genomic data from 289 patients and a panel of cancer cell lines, we
      explored genome-wide expression changes that underlie the evolution of OVCA
      chemoresistance and characterized the BCL2 antagonist of cell death (BAD)
      apoptosis pathway as a determinant of chemosensitivity and patient survival.
      EXPERIMENTAL DESIGN: Serial OVCA cell cisplatin treatments were performed in
      parallel with measurements of genome-wide expression changes. Pathway analysis
      was carried out on genes associated with increasing cisplatin resistance
      (EC(50)). BAD-pathway expression and BAD protein phosphorylation were evaluated
      in patient samples and cell lines as determinants of chemosensitivity and/or
      clinical outcome and as therapeutic targets. RESULTS: Induced in vitro OVCA
      cisplatin resistance was associated with BAD-pathway expression (P < 0.001). In
      OVCA cell lines and primary specimens, BAD protein phosphorylation was associated
      with platinum resistance (n = 147, P < 0.0001) and also with overall patient
      survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels
      influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with
      in vitro phosphorylated BAD levels and with survival in 142 patients with
      advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD
      pathway score with OVCA surgical cytoreductive status was significantly
      associated with overall survival by log-rank test (P = 0.004 and P < 0.0001,
      respectively). CONCLUSION: The BAD apoptosis pathway influences OVCA
      chemosensitivity and overall survival, likely via modulation of BAD
      phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic
      response, patient survival, and as a promising therapeutic target.

PMID- 21849419
TI  - Hydroxyapatite for keratoprosthesis biointegration.
AB  - PURPOSE: Integration of keratoprosthesis with the surrounding cornea is very
      important in preventing bacterial invasion, which may cause ocular injury. Here
      the authors investigated whether hydroxyapatite (HAp) coating can improve
      keratoprosthesis (KPro) biointegration, using polymethyl methacrylate (PMMA)--the
      principal component of the Boston KPro--as a model polymer. METHODS: HAp coatings
      were induced on PMMA discs after treatment with concentrated NaOH and coating
      with poly-dopamine (PDA) or polydopamine and then with 11-mercaptoundecanoic acid
      (11-MUA). Coatings were characterized chemically (Fourier transform infrared
      spectroscopy [FTIR], energy dispersive X-ray spectroscopy [EDX]) and
      morphologically (SEM) and were used as substrates for keratocyte growth in vitro.
      Cylinders of coated PMMA were implanted in porcine corneas ex vivo for 2 weeks,
      and the force required to pull them out was measured. The inflammatory reaction
      to coated discs was assessed in the rabbit cornea in vivo. RESULTS: FTIR of the
      coatings showed absorption bands characteristic of phosphate groups, and EDX
      showed that the Ca/P ratios were close to those of HAp. By SEM, each method
      resulted in morphologically distinct HAp films; the 11-MUA group had the most
      uniform coating. The hydroxyapatite coatings caused comparable enhancement of
      keratocyte proliferation compared with unmodified PMMA surfaces. HAp coating
      significantly increased the force and work required to pull PMMA cylinders out of
      porcine corneas ex vivo. HAp coating of implants reduced the inflammatory
      response around the PMMA implants in vivo. CONCLUSIONS: These results are
      encouraging for the potential of HAp-coated surfaces for use in keratoprostheses.

PMID- 21849421
TI  - Polyhexamethylene biguanide and calcineurin inhibitors as novel antifungal
      treatments for Aspergillus keratitis.
AB  - PURPOSE: To establish polyhexamethylene biguanide (PHMB) as an effective
      treatment for Aspergillus keratitis in a novel murine model. To determine the
      ability of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine A (CSA)
      to enhance the activity of PHMB, amphotericin B (AMB), and voriconazole (VCZ)
      against Aspergillus keratitis. METHODS:  IN VITRO STUDIES: Broth antifungal
      susceptibility tests were performed with PHMB, AMB, VCZ, and FK506, individually
      and in combination against Aspergillus fumigatus. Minimum inhibitory
      concentrations (MIC) and fractional inhibitory concentration index (FICI) values
      were used to analyze antifungal activity. In vivo studies: A novel murine model
      was created to establish Aspergillus keratitis. Infected mice were randomly
      assigned to treatment groups receiving saline, CSA, AMB, VCZ, PHMB, AMB+CSA,
      VCZ+CSA, or PHMB+CSA. An ophthalmologist blinded to the treatment groups assessed
      disease severity daily based on a grading scale. The mean end change in disease
      score was compared between groups. RESULTS:  IN VITRO STUDIES: FK506 in
      combination with PHMB, VCZ, or AMB enhanced fungal growth inhibition. FICI values
      showed an additive effect between FK506 and PHMB, AMB, or VCZ. PHMB monotherapy
      eliminated Aspergillus growth starting at 4 MUg/mL. In vivo studies: All
      treatment groups showed a significant improvement in disease score compared to
      the control group. CSA significantly worsened VCZ activity against Aspergillus
      keratitis. CONCLUSIONS: PHMB is an effective inhibitor of Aspergillus growth.
      Further investigation of the role of calcineurin inhibitors in the treatment for
      Aspergillus keratitis is warranted.

PMID- 21849420
TI  - Analysis of the composition of lipid in human meibum from normal infants,
      children, adolescents, adults, and adults with meibomian gland dysfunction using
      1H-NMR spectroscopy.
AB  - PURPOSE: This study represents a first step toward the evaluation of possible
      compositional differences in meibum from normal donors (Mn) and donors with
      meibomian gland dysfunction (Md) by (1)H-NMR spectroscopy. The results highlight
      the applicability of (1)H-NMR spectroscopy for the quantitative analysis of
      waxes, cholesteryl esters, and glycerides in meibum lipid (ML). METHODS: Meibum
      was obtained from 41 normal donors and 51 donors with meibomian gland dysfunction
      (MGD). (1)H-NMR spectroscopy was used to quantify the amount of waxes,
      glycerides, and cholesteryl esters in human meibum. RESULTS: The relative amount
      of cholesteryl esters in Mn increased with age and was 40% (P < 0.05) lower in
      Md. Interestingly, the relative levels of cholesteryl esters in infant meibum
      were comparable to those in Md. The relative amounts of glycerides were not
      affected significantly by age or MGD. CONCLUSIONS: The changes in cholesteryl
      ester could be used as a molecular marker for MGD and could potentially be
      applied to follow the efficacy of drug therapy in the treatment of MGD. The
      similarity of the levels of cholesteryl esters in infant meibum and Md suggests
      that the relative amounts of these meibum components alone are unlikely to be
      responsible for the increased stability of the infant tear film and decreased
      stability of the tear film with MGD. This study reveals the complexity of human
      MLs and the changes that occur with age and disease. Understanding the factors
      that lead to such variations is of utmost relevance in the design of effective
      therapies.

PMID- 21849422
TI  - Macular pigment optical density in a South Indian population.
AB  - PURPOSE. To estimate the normal value of macular pigment optical density (MPOD)
      in an adult south Indian sample. METHODS. Three hundred eyes of 161 healthy
      volunteers (30 men and 30 women in each of the age groups of 20-29, 30-39, 40-49,
      50-59, and >=60 years) underwent MPOD measurement with a macular densitometer.
      Thirty-two eyes were also checked for intersession variability. RESULTS. The mean
      MPODs in the Indian sample were 0.64 +/- 0.23 log unit at 0.25 degrees 
      eccentricity, 0.50 +/- 0.21 log unit at 0.5 degrees , 0.37 +/- 0.19 log unit at
      1.00 degrees , and 0.21 +/- 0.16 log unit at 1.75 degrees . At all the foveal
      eccentricities, the MPOD showed an increase from 20 to 29 to 30 to 39 years of
      age and thereby showed a decrease with age. The men aged 40 to 49 years had
      significantly higher MPOD than did the women (0.75 vs. 0.62 log unit, P = 0.039),
      and the women aged 50 to 59 years had higher MPOD than did the men (0.71 vs. 0.57
      log unit, P = 0.019). There was no significant intersession or interocular
      variation. CONCLUSIONS. This study establishes the MPOD normogram in an adult
      Indian sample.

PMID- 21849423
TI  - Inducers of cross-linked actin networks in trabecular meshwork cells.
AB  - PURPOSE: It is well established that the unusual actin arrangements known as
      cross-linked actin networks (CLANs) can be induced by dexamethasone (DEX) in
      trabecular meshwork (TM) cells. Recent work reporting their presence in elderly
      glaucomatous and nonglaucomatous tissue, however, has highlighted the presence of
      other inducers. In this study, the authors sought to identify CLAN induction
      agents that may be present within and around the outflow system. METHODS: Studies
      were conducted on confluent bovine TM (BTM) cells in culture, and actin was
      stained with Alexa-Fluor 488 phalloidin to identify CLANs in the target cells.
      The CLAN-inducing potential of aqueous humor was expanded and included
      investigation of transforming growth factor-beta 2 (TGF-beta2). The effect of
      decorin and fetal calf serum (FCS) on BTM cell cytoskeleton was also
      investigated, and all were compared with DEX with an exposure period of up to 7
      days. RESULTS: CLAN numbers were increased after 7 days of exposure to TGF-beta2
      (45%), aqueous humor (37%), and decorin (69%). Even FCS had some modest CLAN
      inducing ability (reaching 12%) in BTM cells. Neutralization of TGF-beta2 reduced
      CLAN incidence in aqueous humor conditions to baseline (12%) levels. Blocking TGF
      beta2 receptors reduced CLAN formation in TM cells by 25% to 30%, whereas the
      inhibition of Smad3 negated CLAN incidence. CONCLUSIONS: In this study the
      authors identified TGF-beta2 as a CLAN-inducing component present in aqueous
      humor. Decorin was also implicated as another CLAN-inducing agent and it was
      confirmed that FCS has CLAN-inducing properties.

PMID- 21849424
TI  - Tear production and ocular surface changes in experimental dry eye after
      elimination of desiccating stress.
AB  - PURPOSE: To investigate the severity and duration of desiccating stress-induced
      dry eye disease between mice with and without a genetic predisposition to
      spontaneous autoimmunity. METHODS: Experimental dry eye was induced in 12- to 16
      week-old wild-type C57BL/6 and autoimmune NOD.B10.H2(b) mice by subcutaneous
      injection of scopolamine with exposure to an air draft for 10 days. Tear volume
      and corneal smoothness were measured at baseline, 5 and 10 days after desiccating
      stress, and 3, 7, 14, and 28 days after the removal of desiccating stress.
      Periodic acid-Schiff staining and immunohistochemistry were performed to evaluate
      the densities of conjunctival goblet cells and CD4(+) T cells in each group.
      Interleukin (IL)-1beta and IL-6 concentrations in conjunctival tissues were
      measured by multiplex immunobead assay. RESULTS: Signs of experimental dry eye
      were noted at 5 and 10 days after desiccating stress in both strains. After the
      removal of desiccating stress, in C57BL/6 mice, tear production and corneal
      smoothness improved at 3 and 7 days, respectively, and conjunctival goblet cells
      and CD4(+) T-cell densities and cytokine levels returned to baseline levels at 14
      days. In contrast, in NOD.B10.H2(b) mice, none of the parameters recovered to
      baseline levels during a period of 28 days after the removal of desiccating
      stress. CONCLUSIONS: After the removal of desiccating stress in experimental dry
      eye, tear volume and ocular surface parameters recovered within 2 weeks in
      C57BL/6 mice, whereas they remained unchanged in NOD mice. In contrast to
      autoimmune mice, experimental dry eye can be reversed after the elimination of
      desiccating stress in nonsusceptible mice.

PMID- 21849426
TI  - Normative database for corneal backscatter analysis by in vivo confocal
      microscopy.
AB  - PURPOSE: To ascertain the sex and age relatedness, diurnal variation, and
      repeatability of backscatter measurement in the normal human cornea. METHODS:
      Seven corneal backscatter variants were measured by in vivo confocal microscopy
      (IVCM) in both normal eyes (n = 314) of 157 healthy subjects. These subjects were
      assigned to one or more of three groups. The sex and age relatedness of corneal
      backscatter were assessed in group 1 (n = 300), which comprised 75 men and 75
      women evenly distributed over five age categories. To assess diurnal variation,
      eyes in group 2 (n = 40) were measured four times a day, at 3-hour intervals. The
      eyes in group 3 (n = 50) were examined four times a year to determine
      intersession repeatability. Intrasession repeatability was determined by
      performing all IVCM examinations in duplicate. Linear mixed models were used to
      assess the effects of sex, age, and time of measurement on corneal backscatter.
      RESULTS: Mean corneal backscatter was 3.5% higher in men (P = 0.003). From the
      age of 50 years, backscatter increased significantly in the anterior stroma (P =
      0.0003). A small but statistically significant diurnal variation was found in all
      seven backscatter variants (P < 0.01). The test-retest coefficient of variation
      of mean corneal backscatter was 5.3%, comprising intra- and intersession
      repeatability. CONCLUSIONS: Sex and time of measurement significantly affect
      corneal backscatter measured by IVCM, whereas age affects only backscatter in the
      anterior stroma. All three factors should be taken into account when conducting
      scientific research. For ophthalmic practice, the authors suggest ignoring these
      factors and propose a generalized normal range and minimum detectable change for
      each backscatter variant.

PMID- 21849425
TI  - Edaravone-loaded liposome eyedrops protect against light-induced retinal damage
      in mice.
AB  - PURPOSE: To investigate the pharmacologic effects of eyedrops containing
      liposomes loaded with edaravone (3-methyl-1-phenyl-2-pyrazolin-5-1) against light
      induced retinal damage in mice. METHODS: Edaravone was incorporated into
      submicron-sized liposomes (ssLips) by the calcium acetate gradient method.
      Retinal damage in mice was induced in dark-adapted mice by exposure to white
      light at 8000 lux for 3 hours. Edaravone-loaded ssLips were dropped into the left
      eye just before and after light exposure and then three times daily for 5 days
      after light exposure. Retinal damage was evaluated by recording the scotopic
      electroretinogram (ERG) and measuring the thickness of the outer nuclear layer
      (ONL) and by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
      staining. The scavenging capacity of reactive oxygen species (ROS) of edaravone
      loaded ssLips was determined using a murine cone photoreceptor cell line (661W).
      The human corneal and conjunctival cell lines were exposed to edaravone-loaded
      ssLips to determine cytotoxicity. RESULTS: Eyedrop administration of edaravone
      loaded ssLips significantly prevented both the decrease in a- and b-wave
      amplitudes of flash ERG and the shrinkage of the ONL compared with the control
      group (treated with empty ssLips) after 5 days of light exposure. The edaravone
      loaded ssLips prevented the increase in the numbers of TUNEL-positive cells after
      48 hours of light exposure. This marked protection was not found in the group
      treated with free edaravone. Edaravone-loaded ssLips showed a stronger inhibition
      of in vitro light-induced ROS production and cell death than did free edaravone.
      The ssLips showed little cytotoxicity toward ocular cell lines. CONCLUSIONS:
      Edaravone-loaded ssLips protected against light-induced retinal dysfunction by
      eyedrop administration. Liposomal eyedrops may become one of the therapeutic
      candidates for drug delivery to posterior eye segments.

PMID- 21849427
TI  - Effects of brief daily periods of unrestricted vision during early monocular form
      deprivation on development of visual area 2.
AB  - PURPOSE: Providing brief daily periods of unrestricted vision during early
      monocular form deprivation reduces the depth of amblyopia. To gain insights into
      the neural basis of the beneficial effects of this treatment, the binocular and
      monocular response properties of neurons were quantitatively analyzed in visual
      area 2 (V2) of form-deprived macaque monkeys. METHODS: Beginning at 3 weeks of
      age, infant monkeys were deprived of clear vision in one eye for 12 hours every
      day until 21 weeks of age. They received daily periods of unrestricted vision for
      0, 1, 2, or 4 hours during the form-deprivation period. After behavioral testing
      to measure the depth of the resulting amblyopia, microelectrode-recording
      experiments were conducted in V2. RESULTS: The ocular dominance imbalance away
      from the affected eye was reduced in the experimental monkeys and was generally
      proportional to the reduction in the depth of amblyopia in individual monkeys.
      There were no interocular differences in the spatial properties of V2 neurons in
      any subject group. However, the binocular disparity sensitivity of V2 neurons was
      significantly higher and binocular suppression was lower in monkeys that had
      unrestricted vision. CONCLUSIONS: The decrease in ocular dominance imbalance in
      V2 was the neuronal change most closely associated with the observed reduction in
      the depth of amblyopia. The results suggest that the degree to which extrastriate
      neurons can maintain functional connections with the deprived eye (i.e., reducing
      undersampling for the affected eye) is the most significant factor associated
      with the beneficial effects of brief periods of unrestricted vision.

PMID- 21849428
TI  - Tumor-associated lymphangiogenesis in the development of conjunctival melanoma.
AB  - PURPOSE: To analyze whether tumor-associated lymphangiogenesis is concurrent with
      the progression of premalignant conjunctival melanocytic intraepithelial
      neoplasia (C-MIN) into invasive conjunctival melanoma (CM) and to study its
      association with prognosis. METHODS: Twenty patients with CM were closely matched
      with 20 patients with C-MIN with atypia and 20 with C-MIN without atypia
      regarding tumor size, tumor location, tumor extension, and patient's age. All
      conjunctival specimens were analyzed for the immunohistochemical presence of
      proliferating lymphatic vessels, with LYVE-1 and podoplanin used as specific
      lymphatic endothelial markers and Ki-67 as a proliferation marker. Lymphatic
      vascular density was measured within the mass (intratumoral) and within an area
      <= 500 MUm from the tumor border (peritumoral) and was correlated with
      recurrence, metastasis, and survival rates. RESULTS: Intratumoral and peritumoral
      proliferating lymphatic vessels were detected in none of the C-MINs without
      atypia, in 10 of the 20 C-MINs with atypia, and in all 20 CMs. Invasive CM showed
      a significantly higher intra- and peritumoral density of proliferating lymphatics
      than did C-MIN with atypia (P <= 0.001). Patients with high intratumoral
      lymphatic density revealed significantly lower recurrence-free survival rates (P
      = 0.041) in C-MIN with atypia and significantly lower recurrence-free (P =
      0.006), lymphatic-spread-free (P = 0.041), distant-metastasis-free (P = 0.029),
      and melanoma-specific survival rates (P = 0.029) in CM. CONCLUSIONS: Development
      of CM from premalignant precursors is concurrent with the outgrowth of lymphatic
      vessels. This active lymphangiogenesis seems to be associated with an increased
      risk of local recurrence in patients with C-MIN with atypia and with an increased
      risk of local recurrence, lymphatic spread, distant metastasis, and tumor-related
      death in patients with invasive CM.

PMID- 21849429
TI  - Deep sequencing of microRNA precursors reveals extensive 3' end modification.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate
      gene expression. An emerging mechanism to control miRNA production is the
      addition of an oligo-uridine tail to the 3' end of the precursor miRNA. This has
      been demonstrated for the Let-7 family of miRNAs in embryonic cells.
      Additionally, nontemplated nucleotides have been found on mature miRNA species,
      though in most cases it is not known if nucleotide addition occurs at the
      precursor step or at the mature miRNA. To examine the diversity of nucleotide
      addition we have developed a high-throughput sequencing method specific for miRNA
      precursors. Here we report that nontemplated addition is a widespread phenomenon
      occurring in many miRNA families. As previously reported, Let-7 family members
      are oligo-uridylated in embryonic cells in a Lin28-dependent manner. However, we
      find that the fraction of uridylated precursors increases with differentiation,
      independent of Lin28, and is highest in adult mouse tissues, exceeding 30% of all
      sequence reads for some Let-7 family members. A similar fraction of sequence
      reads are modified for many other miRNA families. Mono-uridylation is most
      common, with cytidine and adenosine modification less frequent but occurring
      above the expected error rate for Illumina sequencing. Nucleotide addition in
      cell lines is associated with 3' end degradation, in contrast to adult tissues,
      where modification occurs predominantly on full-length precursors. This work
      provides an unprecedented view of the complexity of 3' modification and trimming
      of miRNA precursors.

PMID- 21849430
TI  - Distal leucines are key functional determinants of Alix-binding simian
      immunodeficiency virus SIV(smE543) and SIV(mac239) type 3 L domains.
AB  - In addition to PTAP L domains, primate lentiviruses carry Alix-binding motifs
      that include the recently described type 3 SREKPYKEVTEDLLHLNSLF sequence. We
      examined the requirements for the type 3 sequence motif in simian
      immunodeficiency virus SIV(smE543) and identified the (499)LNSLF(503) sequence as
      a key functional determinant. Mutation of distal leucines (499)L and (502)L (LL
      mutant) caused an inhibitory effect on Alix-dependent SIV(smE543) release that
      was quantitatively similar to that observed following disruption of the type 3 L
      domain or RNA interference (RNAi) depletion of Alix. Similar results were
      obtained with the SIV(mac239) LL mutant. Thus, distal leucines are key
      determinants of SIV(smE543) and SIV(mac239) type 3 L domains.

PMID- 21849431
TI  - High-risk human papillomaviruses repress constitutive kappa interferon
      transcription via E6 to prevent pathogen recognition receptor and antiviral-gene
      expression.
AB  - Persistent infections with human papillomavirus type 16 (HPV16), HPV18, or HPV31
      are necessary for the development of cervical cancer, implying that HPVs have
      evolved immunoevasive mechanisms. Recent global transcriptome analyses indicated
      that these HPV types downregulate the constitutive expression of interferon (IFN)
      stimulated genes (ISGs), but the underlying mechanism is not well understood.
      Comparative analyses of ISG transcription in keratinocytes with complete HPV16, 
      18, and -31 genomes revealed that antiviral genes (IFIT1 and MX1), genes involved
      in IFN signaling (STAT1), proapoptotic genes (TRAIL and XAF1), and pathogen
      recognition receptors (TLR3, RIG-I, and MDA5) are inhibited to similar extents by
      HPV16, -18, and -31. The lower expression of pathogen receptors in HPV-positive
      cells correlated with a greatly impaired induction of IFN-beta and also of IFN
      lambda1, -2, and -3 upon receptor stimulation. IFN-kappa is constitutively
      expressed in normal keratinocytes and is strongly repressed by HPV16, -18, and 
      31. ISGs downregulated in HPV-positive cells can be reactivated by IFN-kappa
      expression. The viral E6 and E7 oncogenes are sufficient for IFN-kappa
      repression, with E6 being mainly responsible. E6 inhibits IFN-kappa transcription
      independently from binding to PDZ proteins. IFN-kappa expression can be activated
      in only one cell line by E6AP knockdown but can be activated in all tested HPV
      positive cells by addition of a DNA methyltransferase inhibitor, suggesting that
      HPVs modulate DNA methylation. Taken together, these results suggest that
      carcinogenic HPVs target IFN-kappa by different pathways in keratinocytes to
      inhibit both antiviral ISGs and pathogen recognition receptors, which in turn
      reduces the expression of inducible IFNs.

PMID- 21849432
TI  - Interaction of reverse transcriptase (RT) mutations conferring resistance to
      lamivudine and etravirine: effects on fitness and RT activity of human
      immunodeficiency virus type 1.
AB  - Resistance to the nonnucleoside reverse transcriptase inhibitors etravirine and
      rilpivirine (RPV) is conferred by the E138K mutation in human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase (RT). Clinical trials of RPV
      administered with lamivudine or emtricitabine showed the emergence of E138K
      together with M184I, which confers lamivudine and emtricitabine resistance in
      most patients with virologic failure. To understand why M184I was favored over
      M184V, we determined the drug susceptibility, infectivity, relative fitness, and
      reverse transcriptase activity of HIV-1 carrying E138K/M184I or E138K/M184V
      mutations. Whereas the replication capacity (RC) of the single mutants was
      reduced compared to that of the wild type (WT), the RC of the two double mutants
      was comparable to that of the WT in the absence of drug. The RC of the
      E138K/M184I mutant in the presence of etravirine was significantly greater than
      that of the E138K and E138K/M184V mutants; the RC of the double mutants was
      greater than that of the M184I or M184V mutant. Fitness profiles and growth
      competition experiments showed that the E138K/M184I mutant had a significant
      replicative advantage over the E138K/M184V mutant in the presence of etravirine
      and lamivudine. The virion-associated RT activity of the E138K, M184I, or M184V
      virus was significantly reduced compared to that of the WT, whereas the RT
      activity of the E138K/M184I virus was significantly greater than that of the WT
      or E138K/M184V virus. These results suggest that the E138K and M184I/V mutations
      are mutually compensatory and may explain the frequent occurrence of E138K/M184I
      after the virologic failure of rilpivirine-, lamivudine-, and emtricitabine
      containing regimens.

PMID- 21849434
TI  - The human papillomavirus type 16 E5 oncoprotein translocates calpactin I to the
      perinuclear region.
AB  - The human papillomavirus type 16 (HPV-16) E5 oncoprotein is embedded in membranes
      of the endoplasmic reticulum and nuclear envelope with its C terminus exposed to
      the cytoplasm. Among other activities, E5 cooperates with the HPV E6 oncoprotein
      to induce koilocytosis in human cervical cells and keratinocytes in vitro. The
      effect of E5 on infected cells may rely on its interactions with various cellular
      proteins. In this study we identify calpactin I, a heterotetrameric, Ca(2+)- and
      phospholipid-binding protein complex that regulates membrane fusion, as a new
      cellular target for E5. Both the annexin A2 and p11 subunits of calpactin I
      coimmunoprecipitate with E5 in COS cells and in human epithelial cell lines, and
      an intact E5 C terminus is required for binding. Moreover, E5-expressing cells
      exhibit a perinuclear redistribution of annexin A2 and p11 and show increased
      fusion of perinuclear membrane vesicles. The C terminus of E5 is required for
      both the perinuclear redistribution of calpactin I and increased formation of
      perinuclear vacuoles. These results support the hypothesis that the E5-induced
      relocalization of calpactin I to the perinuclear region promotes perinuclear
      membrane fusion, which may underlie the development of koilocytotic vacuoles.

PMID- 21849435
TI  - Juxtaposition of two distant, serine-arginine-rich protein-binding elements is
      required for optimal polyadenylation in Rous sarcoma virus.
AB  - The Rous sarcoma virus (RSV) polyadenylation site (PAS) is very poorly used in
      vitro due to suboptimal upstream and downstream elements, and yet ~85% of viral
      transcripts are polyadenylated in vivo. The mechanisms that orchestrate
      polyadenylation at the weak PAS are not completely understood. It was previously
      shown that serine-arginine (SR)-rich proteins stimulate RSV PAS use in vitro and
      in vivo. It has been proposed that viral RNA polyadenylation is stimulated
      through a nonproductive splice complex that forms between a pseudo 5' splice site
      (5'ss) within the negative regulator of splicing (NRS) and a downstream 3'ss,
      which repositions NRS-bound SR proteins closer to the viral PAS. This
      repositioning is thought to be important for long-distance poly(A) stimulation by
      the NRS. We report here that a 308-nucleotide deletion downstream of the env 3'ss
      decreased polyadenylation efficiency, suggesting the presence of an additional
      element required for optimal RSV polyadenylation. Mapping studies localized the
      poly(A) stimulating element to a region coincident with the Env splicing
      enhancer, which binds SR proteins, and inactivation of the enhancer and SR
      protein binding decreased polyadenylation efficiency. The positive effect of the
      Env enhancer on polyadenylation could be uncoupled from its role in splicing. As
      with the NRS, the Env enhancer also stimulated use of the viral PAS in vitro.
      These results suggest that a critical threshold of SR proteins, achieved by
      juxtaposition of SR protein binding sites within the NRS and Env enhancer, is
      required for long-range polyadenylation stimulation.

PMID- 21849433
TI  - Antigen-dependent and -independent mechanisms of T and B cell hyperactivation
      during chronic HIV-1 infection.
AB  - Continuous loss of CD4(+) T lymphocytes and systemic immune activation are
      hallmarks of untreated chronic HIV-1 infection. Chronic immune activation during
      HIV-1 infection is characterized by increased expression of activation markers on
      T cells, elevated levels of proinflammatory cytokines, and B cell hyperactivation
      together with hypergammaglobulinemia. Importantly, hyperactivation of T cells is
      one of the best predictive markers for progression toward AIDS, and it is closely
      linked to CD4(+) T cell depletion and sustained viral replication. Aberrant
      activation of T cells is observed mainly for memory CD4(+) and CD8(+) T cells and
      is documented, in addition to increased expression of surface activation markers,
      by increased cell cycling and apoptosis. Notably, the majority of these activated
      T cells are neither HIV specific nor HIV infected, and the antigen specificities
      of hyperactivated T cells are largely unknown, as are the exact mechanisms
      driving their activation. B cells are also severely affected by HIV-1 infection,
      which is manifested by major changes in B cell subpopulations, B cell
      hyperactivation, and hypergammaglobulinemia. Similar to those of T cells, the
      mechanisms underlying this aberrant B cell activation remain largely unknown. In
      this review, we summarized current knowledge about proposed antigen-dependent and
      -independent mechanisms leading to lymphocyte hyperactivation in the context of
      HIV-1 infection.

PMID- 21849436
TI  - Replication and transcription activator (RTA) of murine gammaherpesvirus 68 binds
      to an RTA-responsive element and activates the expression of ORF18.
AB  - The replication and transcription activator (RTA), mainly encoded by open reading
      frame 50, is an immediate-early gene product that is conserved among all
      characterized gammaherpesviruses. Previous studies have demonstrated that RTA
      proteins of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus
      (KSHV) can activate the promoter of many viral early lytic genes through direct
      or indirect mechanisms. Murine gammaherpesvirus 68 (MHV-68) is genetically
      related to KSHV and EBV, and the RTA homologue from MHV-68 also initiates the
      lytic cycle of gene expression. Although two RTA-dependent promoters had been
      identified in MHV-68, the mechanism of the interaction between RTA and the
      promoters was not characterized. In this study, we first identified an RTA
      responsive promoter in the left origin of lytic replication region of MHV-68
      through a reporter assay and mapped a 27-bp RTA-responsive element (RRE) through
      systematic deletions. Interestingly, sequence analysis identified a second RRE in
      this region. An electrophoretic mobility shift assay (EMSA) and a chromatin
      immunoprecipitation (ChIP) assay showed that RTA can bind directly to these two
      RREs in vitro or in vivo. Mutagenesis studies have further characterized the
      nucleotides important for mediating RTA binding by an EMSA. Moreover, we
      engineered RRE-deleted viruses and demonstrated in the context of the viral
      genome that one of the RREs mediates the RTA-dependent activation of an essential
      lytic gene, ORF18, during de novo infection. To our knowledge, this is the first
      time that RTA binding sites in MHV-68 have been identified. Since ORF18 regulates
      viral late gene expression, our study has also contributed to the delineation of
      the expression cascade of gammaherpesvirus lytic genes.

PMID- 21849437
TI  - Human herpesvirus 6 glycoprotein complex formation is required for folding and
      trafficking of the gH/gL/gQ1/gQ2 complex and its cellular receptor binding.
AB  - Human herpesvirus 6 (HHV-6) is a T-cell-tropic betaherpesvirus. A glycoprotein
      (g) complex that is unique to HHV-6, gH/gL/gQ1/gQ2, is a viral ligand for its
      cellular receptor, human CD46. However, whether complex formation or one
      component of the complex is required for CD46 binding and how the complex is
      transported in cells are open questions. Furthermore, in HHV-6-infected cells the
      gQ1 protein modified with N-linked glycans is expressed in two forms with
      different molecular masses: an 80-kDa form (gQ1-80K) and a 74-kDa form (gQ1-74K).
      Only gQ1-80K, but not gQ1-74K, forms the complex with gQ2, gH, and gL, and this
      four-component complex is incorporated into mature virions. Here, we
      characterized the molecular context leading to the maturation of gQ1 by
      expressing combinations of the individual gH/gL/gQ1/gQ2 components in 293T cells.
      Surprisingly, only when all four molecules were expressed was a substantial
      amount of gQ1-80K detected, indicating that all three of the other molecules
      (gQ2, gH, and gL) were necessary and sufficient for gQ1 maturation. We also found
      that only the tetrameric complex, and not its subsets, binds to CD46. Finally, a
      gQ2-null virus constructed in the BAC (bacterial artificial chromosome) system
      could not be reconstituted, indicating that gQ2 is essential for virus growth.
      These results show that gH, gL, gQ1, and gQ2 are all essential for the
      trafficking and proper folding of the gH/gL/gQ1/gQ2 complex and, thus, for HHV-6
      infection.

PMID- 21849438
TI  - Antimycotic-antibiotic amphotericin B promotes influenza virus replication in
      cell culture.
AB  - In general, antibiotics are not rated as substances that inhibit or support
      influenza virus replication. We describe here the enhancing effect of the polyene
      antibiotic amphotericin B (AmB) on influenza virus growth in Vero cells. We show
      that isolation rates of influenza A and B viruses from clinical samples can be
      dramatically enhanced by adding AmB to the culture medium. We demonstrate that
      AmB promotes the viral uptake and endocytic processing of the virus particles.
      This effect is specific for Vero and human nasal epithelial cells and was not
      observed in Madin-Darby canine kidney cells. The effect of AmB was subtype
      specific and more prominent for human seasonal influenza strains but absent for
      H5N1 human viruses. The AmB-enhancing effect seemed to be solely due to the viral
      hemagglutinin function. Our results indicate that the use of AmB may facilitate
      influenza virus isolation and production in Vero cells.

PMID- 21849439
TI  - Canine distemper virus infects canine keratinocytes and immune cells by using
      overlapping and distinct regions located on one side of the attachment protein.
AB  - The morbilliviruses measles virus (MeV) and canine distemper virus (CDV) both
      rely on two surface glycoproteins, the attachment (H) and fusion proteins, to
      promote fusion activity for viral cell entry. Growing evidence suggests that
      morbilliviruses infect multiple cell types by binding to distinct host cell
      surface receptors. Currently, the only known in vivo receptor used by
      morbilliviruses is CD150/SLAM, a molecule expressed in certain immune cells. Here
      we investigated the usage of multiple receptors by the highly virulent and
      demyelinating CDV strain A75/17. We based our study on the assumption that CDV-H
      may interact with receptors similar to those for MeV, and we conducted systematic
      alanine-scanning mutagenesis on CDV-H throughout one side of the beta-propeller
      documented in MeV-H to contain multiple receptor-binding sites. Functional and
      biochemical assays performed with SLAM-expressing cells and primary canine
      epithelial keratinocytes identified 11 residues mutation of which selectively
      abrogated fusion in keratinocytes. Among these, four were identical to amino
      acids identified in MeV-H as residues contacting a putative receptor expressed in
      polarized epithelial cells. Strikingly, when mapped on a CDV-H structural model,
      all residues clustered in or around a recessed groove located on one side of CDV
      H. In contrast, reported CDV-H mutants with SLAM-dependent fusion deficiencies
      were characterized by additional impairments to the promotion of fusion in
      keratinocytes. Furthermore, upon transfer of residues that selectively impaired
      fusion induction in keratinocytes into the CDV-H of the vaccine strain, fusion
      remained largely unaltered. Taken together, our results suggest that a restricted
      region on one side of CDV-H contains distinct and overlapping sites that control
      functional interaction with multiple receptors.

PMID- 21849440
TI  - Epstein-Barr virus latent membrane protein 1 induces cancer stem/progenitor-like
      cells in nasopharyngeal epithelial cell lines.
AB  - Recent studies suggest the existence of cancer stem cells (CSC) and cancer
      progenitor cells (CPC), although strict definitions of neither CSC nor CPC have
      been developed. We have produced evidence that the principal oncoprotein of
      Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), which is associated
      with human malignancies, especially nasopharyngeal carcinoma (NPC), promotes
      tumor cell invasion and metastasis, as well as the epithelial-mesenchymal
      transition (EMT). However, whether LMP1 is involved in the development of CSC/CPC
      is still unclear. This study investigates whether the expression of EBV-LMP1 is
      related to the development of CSC/CPC. Analysis of cancer stem cell markers
      reveals that LMP1 induces the CD44(high) CD24(low) CSC/CPC-like phenotype as well
      as self-renewal abilities in LMP1-expressing epithelial cell lines. In addition,
      we show here that LMP1 induction in epithelial cells causes high tumorigenicity
      and rapid cellular proliferation. Furthermore, we found that LMP1 expression
      increased the expression of several CPC markers as well as producing increased
      levels of EMT markers. Our findings indicate that LMP1 can induce a CPC-like
      rather than a CSC-like phenotype in epithelial cells and suggest that LMP1
      induced phenotypic changes contribute to the development of NPC.

PMID- 21849442
TI  - Novel reassortment of Eurasian avian-like and pandemic/2009 influenza viruses in
      swine: infectious potential for humans.
AB  - Pigs are considered to be intermediate hosts and "mixing vessels," facilitating
      the genesis of pandemic influenza viruses, as demonstrated by the emergence of
      the 2009 H1N1 pandemic (pdm/09) virus. The prevalence and repeated introduction
      of the pdm/09 virus into pigs raises the possibility of generating novel swine
      influenza viruses with the potential to infect humans. To address this, an active
      influenza surveillance program was conducted with slaughtered pigs in abattoirs
      in southern China. Over 50% of the pigs tested were found to be seropositive for
      one or more H1 influenza viruses, most commonly pdm/09-like viruses. Out of 36
      virus isolates detected, one group of novel reassortants had Eurasian avian-like
      swine H1N1 surface genes and pdm/09 internal genes. Animal experiments showed
      that this virus transmitted effectively from pig to pig and from pig to ferret,
      and it could also replicate in ex vivo human lung tissue. Immunization against
      the 2009 pandemic virus gave only partial protection to ferrets. The continuing
      prevalence of the pdm/09 virus in pigs could lead to the genesis of novel swine
      reassortant viruses with the potential to infect humans.

PMID- 21849441
TI  - Nuclear receptor signaling inhibits HIV-1 replication in macrophages through
      multiple trans-repression mechanisms.
AB  - Sexually transmitted pathogens activate HIV-1 replication and inflammatory gene
      expression in macrophages through engagement of Toll-like receptors (TLRs).
      Ligand-activated nuclear receptor (NR) transcription factors, including
      glucocorticoid receptor (GR), peroxisome proliferator-activated receptor gamma
      (PPARgamma), and liver X receptor (LXR), are potent inhibitors of TLR-induced
      inflammatory gene expression. We therefore hypothesized that ligand-activated NRs
      repress both basal and pathogen-enhanced HIV-1 replication in macrophages by
      directly repressing HIV-1 transcription and by ameliorating the local
      proinflammatory response to pathogens. We show that the TLR2 ligand PAM3CSK4
      activated virus transcription in macrophages and that NR signaling repressed both
      basal and TLR-induced HIV-1 transcription. NR ligand treatment repressed HIV-1
      expression when added concurrently with TLR ligands and in the presence of
      cycloheximide, demonstrating that they act independently of new cellular gene
      expression. We found that treatment with NR ligands inhibited the association of
      AP-1 and NF-kappaB subunits, as well as the coactivator CBP, with the long
      terminal repeat (LTR). We show for the first time that the nuclear corepressor
      NCoR is bound to HIV-1 LTR in unstimulated macrophages and is released from the
      LTR after TLR engagement. Treatment with PPARgamma and LXR ligands, but not GR
      ligands, prevented this TLR-induced clearance of NCoR from the LTR. Our data
      demonstrate that both classical and nonclassical trans-repression mechanisms
      account for NR-mediated HIV-1 repression. Finally, NR ligand treatment inhibited
      the potent proinflammatory response induced by PAM3CSK4 that would otherwise
      activate HIV-1 expression in infected cells. Our findings provide a rationale for
      studying ligand-activated NRs as modulators of basal and inflammation-induced HIV
      1 replication.

PMID- 21849443
TI  - Phylogenetic analysis of murine leukemia virus sequences from longitudinally
      sampled chronic fatigue syndrome patients suggests PCR contamination rather than
      viral evolution.
AB  - Xenotropic murine leukemia virus (MLV)-related virus (XMRV) has been amplified
      from human prostate cancer and chronic fatigue syndrome (CFS) patient samples.
      Other studies failed to replicate these findings and suggested PCR contamination
      with a prostate cancer cell line, 22Rv1, as a likely source. MLV-like sequences
      have also been detected in CFS patients in longitudinal samples 15 years apart.
      Here, we tested whether sequence data from these samples are consistent with
      viral evolution. Our phylogenetic analyses strongly reject a model of within
      patient evolution and demonstrate that the sequences from the first and second
      time points represent distinct endogenous murine retroviruses, suggesting
      contamination.

PMID- 21849444
TI  - Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in
      viral replication capacity and enzyme processivity associated with the M184I/V
      mutations.
AB  - Recently, several phase 3 clinical trials (ECHO and THRIVE) showed that E138K and
      M184I were the most frequent mutations to emerge in patients who failed therapy
      with rilpivirine (RPV) together with two nucleos(t)ide reverse transcriptase
      inhibitors, emtricitabine (FTC) and tenofovir (TDF). To investigate the basis for
      the copresence of E138K and M184I, we generated recombinant mutated and wild-type
      (WT) reverse transcriptase (RT) enzymes and HIV-1(NL4-3) infectious clones. Drug
      susceptibilities were determined in cord blood mononuclear cells (CBMCs).
      Structural modeling was performed to analyze any impact on deoxynucleoside
      triphosphate (dNTP) binding. The results of phenotyping showed that viruses
      containing both the E138K and M184V mutations were more resistant to each of FTC,
      3TC, and ETR than viruses containing E138K and M184I. Viruses with E138K
      displayed only modest resistance to ETR, little resistance to efavirenz (EFV),
      and no resistance to either FTC or 3TC. E138K restored viral replication capacity
      (RC) in the presence of M184I/V, and this was confirmed in cell-free RT
      processivity assays. RT enzymes containing E138K, E138K/184I, or E138K/184V
      exhibited higher processivity than WT RT at low dNTP concentrations. Steady-state
      kinetic analysis demonstrated that the E138K mutation resulted in decreased K(m)s
      for dNTPs. In contrast, M184I/V resulted in an increased K(m) for dNTPs compared
      to those for WT RT. These results indicate that the E138K mutation compensates
      for both the deficit in dNTP usage and impairment in replication capacity by
      M184I/V. Structural modeling shows that the addition of E138K to M184I/V promotes
      tighter dNTP binding.

PMID- 21849445
TI  - The ectromelia virus SPI-2 protein causes lethal mousepox by preventing NK cell
      responses.
AB  - Ectromelia virus (ECTV) is a natural pathogen of mice that causes mousepox, and
      many of its genes have been implicated in the modulation of host immune
      responses. Serine protease inhibitor 2 (SPI-2) is one of these putative ECTV host
      response modifier proteins. SPI-2 is conserved across orthopoxviruses, but
      results defining its mechanism of action and in vivo function are lacking or
      contradictory. We studied the role of SPI-2 in mousepox by deleting the SPI-2
      gene or its serine protease inhibitor reactive site. We found that SPI-2 does not
      affect viral replication or cell-intrinsic apoptosis pathways, since mutant
      viruses replicate in vitro as efficiently as wild-type virus. However, in the
      absence of SPI-2 protein, ECTV is attenuated in mousepox-susceptible mice,
      resulting in lower viral loads in the liver, decreased spleen pathology, and
      substantially improved host survival. This attenuation correlates with more
      effective immune responses in the absence of SPI-2, including an earlier serum
      gamma interferon (IFN-gamma) response, raised serum interleukin 18 (IL-18),
      increased numbers of granzyme B(+) CD8(+) T cells, and, most notably, increased
      numbers and activation of NK cells. Both virus attenuation and the improved
      immune responses associated with SPI-2 deletion from ECTV are lost when mice are
      depleted of NK cells. Consequently, SPI-2 renders mousepox lethal in susceptible
      strains by preventing protective NK cell defenses.

PMID- 21849446
TI  - De novo infection of B cells during murine gammaherpesvirus 68 latency.
AB  - The mechanisms by which gammaherpesviruses maintain latency are unclear. Here we
      used a murine gammaherpesvirus model to show that previously uninfected B cells
      in immunocompetent mice can acquire virus during latency. In vivo depletion of T
      cells allowed viral reactivation, as measured by increased viral loads, but not
      enhanced transfer of virus to new cells. In the absence of both immune T cells
      and antibody following the transfer of latently infected cells into naive
      animals, there was robust infection of new B cells. These data confirm that both
      T cells and antibody contribute to the control of gammaherpesvirus latency,
      reactivation, and spread.

PMID- 21849447
TI  - A broadly neutralizing human monoclonal antibody that recognizes a conserved,
      novel epitope on the globular head of the influenza H1N1 virus hemagglutinin.
AB  - The conserved influenza virus hemagglutinin (HA) stem domain elicits cross
      reactive antibodies, but epitopes in the globular head typically elicit strain
      specific responses because of the hypervariability of this region. We isolated
      human monoclonal antibody 5J8, which neutralized a broad spectrum of 20th century
      H1N1 viruses and the 2009 pandemic H1N1 virus. Fine mapping of the interaction
      unexpectedly revealed a novel epitope between the receptor-binding pocket and the
      Ca2 antigenic site on HA. This antibody exposes a new mechanism underlying broad
      immunity against H1N1 influenza viruses and identifies a conserved epitope that
      might be incorporated into engineered H1 virus vaccines.

PMID- 21849448
TI  - Determining the frequency and mechanisms of HIV-1 and HIV-2 RNA copackaging by
      single-virion analysis.
AB  - HIV-1 and HIV-2 are derived from two distinct primate viruses and share only
      limited sequence identity. Despite this, HIV-1 and HIV-2 Gag polyproteins can
      coassemble into the same particle and their genomes can undergo recombination,
      albeit at an extremely low frequency, implying that HIV-1 and HIV-2 RNA can be
      copackaged into the same particle. To determine the frequency of HIV-1 and HIV-2
      RNA copackaging and to dissect the mechanisms that allow the heterologous RNA
      copackaging, we directly visualized the RNA content of each particle by using RNA
      binding proteins tagged with fluorescent proteins to label the viral genomes. We
      found that when HIV-1 and HIV-2 RNA are present in viral particles at similar
      ratios, ~10% of the viral particles encapsidate both HIV-1 and HIV-2 RNAs.
      Furthermore, heterologous RNA copackaging can be promoted by mutating the 6
      nucleotide (6-nt) dimer initiation signal (DIS) to discourage RNA
      homodimerization or to encourage RNA heterodimerization, indicating that HIV-1
      and HIV-2 RNA can heterodimerize prior to packaging using the DIS sequences. We
      also observed that the coassembly of HIV-1 and HIV-2 Gag proteins is not required
      for the heterologous RNA copackaging; HIV-1 Gag proteins are capable of mediating
      HIV-1 and HIV-2 RNA copackaging. These results define the cis- and trans-acting
      elements required for and affecting the heterologous RNA copackaging, a
      prerequisite for the generation of chimeric viruses by recombination, and also
      shed light on the mechanisms of RNA-Gag recognition essential for RNA
      encapsidation.

PMID- 21849449
TI  - Inhibition of retromer activity by herpesvirus saimiri tip leads to CD4
      downregulation and efficient T cell transformation.
AB  - The mammalian retromer is an evolutionally conserved protein complex composed of
      a vacuolar protein sorting trimer (Vps 26/29/35) that participates in cargo
      recognition and a sorting nexin (SNX) dimer that binds to endosomal membranes.
      The retromer plays an important role in efficient retrograde transport for
      endosome-to-Golgi retrieval of the cation-independent mannose-6-phosphate
      receptor (CI-MPR), a receptor for lysosomal hydrolases, and other endosomal
      proteins. This ultimately contributes to the control of cell growth, cell
      adhesion, and cell migration. The herpesvirus saimiri (HVS) tyrosine kinase
      interacting protein (Tip), required for the immortalization of primary T
      lymphocytes, targets cellular signaling molecules, including Lck tyrosine kinases
      and the p80 endosomal trafficking protein. Despite the pronounced effects of HVS
      Tip on T cell signal transduction, the details of its activity on T cell
      immortalization remain elusive. Here, we report that the amino-terminal
      conserved, glutamate-rich sequence of Tip specifically interacts with the
      retromer subunit Vps35 and that this interaction not only causes the
      redistribution of Vps35 from the early endosome to the lysosome but also
      drastically inhibits retromer activity, as measured by decreased levels of CI-MPR
      and lower activities of cellular lysosomal hydrolases. Physiologically, the
      inhibition of intracellular retromer activity by Tip is ultimately linked to the
      downregulation of CD4 surface expression and to the efficient in vitro
      immortalization of primary human T cells to interleukin-2 (IL-2)-independent
      permanent growth. Therefore, HVS Tip uniquely targets the retromer complex to
      impair the intracellular trafficking functions of infected cells, ultimately
      contributing to efficient T cell transformation.

PMID- 21849450
TI  - A panel of IgG1 b12 variants with selectively diminished or enhanced affinity for
      Fcgamma receptors to define the role of effector functions in protection against
      HIV.
AB  - Passive transfer of neutralizing antibodies is effective in protecting rhesus
      macaques against simian/human immunodeficiency virus (SHIV) challenge. In
      addition to neutralization, effector functions of the crystallizable fragment
      (Fc) of antibodies are involved in antibody-mediated protection against a number
      of viruses. We recently showed that interaction between the Fc fragment of the
      broadly neutralizing antibody IgG1 b12 and cellular Fcgamma receptors (FcgammaRs)
      plays an important role in protection against SHIV infection in rhesus macaques.
      The specific nature of this Fc-dependent protection is largely unknown. To
      investigate, we generated a panel of 11 IgG1 b12 antibody variants with
      selectively diminished or enhanced affinity for the two main activating
      FcgammaRs, FcgammaRIIa and FcgammaRIIIa. All 11 antibody variants bind gp120 and
      neutralize virus as effectively as does wild-type b12. Binding studies using
      monomeric (enzyme-linked immunosorbent assay [ELISA] and surface plasmon
      resonance [SPR]) and cellularly expressed Fcgamma receptors show decreased (up to
      5-fold) and increased (up to 90-fold) binding to FcgammaRIIa and FcgammaRIIIa
      with this newly generated panel of antibodies. In addition, there was generally a
      good correlation between b12 variant affinity for Fcgamma receptor and variant
      function in antibody-dependent cell-mediated virus inhibition (ADCVI),
      phagocytosis, NK cell activation assays, and antibody-dependent cellular
      cytotoxicity (ADCC) assays. In future studies, these b12 variants will enable the
      investigation of the protective role of individual FcgammaRs in HIV infection.

PMID- 21849451
TI  - Comparative analysis of avian influenza virus diversity in poultry and humans
      during a highly pathogenic avian influenza A (H7N7) virus outbreak.
AB  - Although increasing data have become available that link human adaptation with
      specific molecular changes in nonhuman influenza viruses, the molecular changes
      of these viruses during a large highly pathogenic avian influenza virus (HPAI)
      outbreak in poultry along with avian-to-human transmission have never been
      documented. By comprehensive virologic analysis of combined veterinary and human
      samples obtained during a large HPAI A (H7N7) outbreak in the Netherlands in
      2003, we mapped the acquisition of human adaptation markers to identify the
      public health risk associated with an HPAI outbreak in poultry. Full-length
      hemagglutinin (HA), neuraminidase (NA), and PB2 sequencing of A (H7N7) viruses
      obtained from 45 human cases showed amino acid variations at different codons in
      HA (n=20), NA (n=23), and PB2 (n=23). Identification of the avian sources of
      human virus infections based on 232 farm sequences demonstrated that for each
      gene about 50% of the variation was already present in poultry. Polygenic
      accumulation and farm-to-farm spread of known virulence and human adaptation
      markers in A (H7N7) virus-infected poultry occurred prior to farm-to-human
      transmission. These include the independent emergence of HA A143T mutants,
      accumulation of four NA mutations, and farm-to-farm spread of virus variants
      harboring mammalian host determinants D701N and S714I in PB2. This implies that
      HPAI viruses with pandemic potential can emerge directly from poultry. Since the
      public health risk of an avian influenza virus outbreak in poultry can rapidly
      change, we recommend virologic monitoring for human adaptation markers among
      poultry as well as among humans during the course of an outbreak in poultry.

PMID- 21849453
TI  - In situ cleavage of baculovirus occlusion-derived virus receptor binding protein
      P74 in the peroral infectivity complex.
AB  - Proteolytic processing of viral membrane proteins is common among enveloped
      viruses and facilitates virus entry. The Autographa californica multicapsid
      nucleopolyhedrovirus (AcMNPV) occlusion-derived virus (ODV) protein P74 is part
      of a complex of essential peroral infectivity factors (PIFs). Here we report that
      P74 is efficiently cleaved into two fragments of about equal size by an occlusion
      body (OB) endogenous alkaline protease during ODV release when AcMNPV OBs are
      derived from larvae. The cleavage is specific for P74, since the other known
      peroral infectivity factors in the same complex (PIF1, PIF2, and PIF3) were not
      cleaved under the same conditions. P74 cleavage was not observed in OBs produced
      in three different insect cell lines, suggesting a larval host origin of the
      responsible protease. P74 in OBs produced in larvae of two different host species
      was cleaved into fragments with the same apparent molecular mass, indicating that
      the virus incorporates a similar alkaline protease from different hosts.
      Coimmunoprecipitation analysis revealed that the two P74 subunit fragments remain
      associated with the recently discovered PIF complex. We propose that under in
      vivo ODV infection conditions, P74 undergoes two sequential cleavage events, the
      first one being performed by an ODV-associated host alkaline protease and the
      second carried out by trypsin in the host midgut.

PMID- 21849452
TI  - Polyclonal B cell responses to conserved neutralization epitopes in a subset of
      HIV-1-infected individuals.
AB  - A small proportion of HIV-infected individuals generate a neutralizing antibody
      (NAb) response of exceptional magnitude and breadth. A detailed analysis of the
      critical epitopes targeted by broadly neutralizing antibodies should help to
      define optimal targets for vaccine design. HIV-1-infected subjects with potent
      cross-reactive serum neutralizing antibodies were identified by assaying sera
      from 308 subjects against a multiclade panel of 12 "tier 2" viruses (4 each of
      subtypes A, B, and C). Various neutralizing epitope specificities were determined
      for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C
      infected donors, by using a comprehensive set of assays. In some subjects,
      neutralization breadth was mediated by two or more antibody specificities.
      Although antibodies to the gp41 membrane-proximal external region (MPER) were
      identified in some subjects, the subjects with the greatest neutralization
      breadth targeted gp120 epitopes, including the CD4 binding site, a glycan
      containing quaternary epitope formed by the V2 and V3 loops, or an outer domain
      epitope containing a glycan at residue N332. The broadly reactive HIV-1
      neutralization observed in some subjects is mediated by antibodies targeting
      several conserved regions on the HIV-1 envelope glycoprotein.

PMID- 21849454
TI  - Norovirus RNA-dependent RNA polymerase is phosphorylated by an important survival
      kinase, Akt.
AB  - Viruses commonly use host cell survival mechanisms to their own advantage. We
      show that Akt, an important signaling kinase involved in cell survival,
      phosphorylates the RNA-dependent RNA polymerase (RdRp) from norovirus, the major
      cause of gastroenteritis outbreaks worldwide. The Akt phosphorylation of RdRp
      appears to be a feature unique to the more prevalent norovirus genotypes such as
      GII.4 and GII.b. This phosphorylation event occurs at a residue (Thr33) located
      at the interface where the RdRp finger and thumb domains interact and decreases
      de novo activity of the polymerase. This finding provides fresh insights into
      virus-host cell interactions.

PMID- 21849455
TI  - Y-box-binding protein 1 interacts with hepatitis C virus NS3/4A and influences
      the equilibrium between viral RNA replication and infectious particle production.
AB  - The hepatitis C virus (HCV) NS3/4A protein has several essential roles in the
      virus life cycle, most probably through dynamic interactions with host factors.
      To discover cellular cofactors that are co-opted by HCV for its replication, we
      elucidated the NS3/4A interactome using mass spectrometry and identified Y-box
      binding protein 1 (YB-1) as an interacting partner of NS3/4A protein and HCV
      genomic RNA. Importantly, silencing YB-1 expression decreased viral RNA
      replication and severely impaired the propagation of the infectious HCV molecular
      clone JFH-1. Immunofluorescence studies further revealed a drastic HCV-dependent
      redistribution of YB-1 to the surface of the lipid droplets, an important
      organelle for HCV assembly. Core and NS3 protein-dependent polyprotein maturation
      were shown to be required for YB-1 relocalization. Unexpectedly, YB-1 knockdown
      cells showed the increased production of viral infectious particles while HCV RNA
      replication was impaired. Our data support that HCV hijacks YB-1-containing
      ribonucleoparticles and that YB-1-NS3/4A-HCV RNA complexes regulate the
      equilibrium between HCV RNA replication and viral particle production.

PMID- 21849456
TI  - Molecular epidemiology of human coronavirus OC43 reveals evolution of different
      genotypes over time and recent emergence of a novel genotype due to natural
      recombination.
AB  - Although human coronavirus OC43-OC43 (HCoV-OC43) is the coronavirus most commonly
      associated with human infections, little is known about its molecular
      epidemiology and evolution. We conducted a molecular epidemiology study to
      investigate different genotypes and potential recombination in HCoV-OC43. Twenty
      nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to
      2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and
      nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct
      clusters of HCoV-OC43, although 10 unusual strains displayed incongruent
      phylogenetic positions between RdRp and spike genes. This suggested the presence
      of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from
      recombination. The complete genome sequencing of two genotype C and D strains and
      bootscan analysis showed recombination events between genotypes B and C in the
      generation of genotype D. Of the 29 strains, none belonged to the more ancient
      genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to
      genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the
      recombinant genotype D. Molecular clock analysis using spike and nucleocapsid
      genes dated the most recent common ancestor of all genotypes to the 1950s,
      genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the
      late 1990s to early 2000s, while the recombinant genotype D strains were detected
      as early as 2004. This represents the first study to describe natural
      recombination in HCoV-OC43 and the evolution of different genotypes over time,
      leading to the emergence of novel genotype D, which is associated with pneumonia
      in our elderly population.

PMID- 21849457
TI  - Upregulation of BST-2/Tetherin by HIV infection in vivo.
AB  - The interferon-inducible antiviral factor BST-2 prevents several enveloped
      viruses, including HIV, from escaping infected cells. The HIV protein Vpu
      antagonizes this host defense. Little is known about the expression of BST-2
      during HIV infection in vivo and whether it can be modulated to the host's
      advantage. We studied the expression of BST-2 on blood cells from HIV-infected
      patients during the acute and chronic phases of disease as well as after
      antiretroviral treatment (ART). The expression of BST-2 was increased on
      mononuclear leukocytes, including CD4-positive T lymphocytes from HIV-positive
      patients, compared to that on cells of uninfected controls. The expression of BST
      2 was highest during acute infection and decreased to levels similar to those of
      uninfected individuals after ART. Treatment of primary blood mononuclear cells in
      vitro with alpha interferon or with Toll-like receptor (TLR) agonists increased
      the expression of BST-2 to levels similar to those found during infection in
      vivo. The interferon-induced levels were sufficient to overcome the Vpu protein
      in vitro, reducing the release of wild-type HIV. These data show that BST-2 is
      upregulated during HIV infection, consistent with its role as an interferon
      stimulated gene. The data further suggest that this upregulation is sufficient to
      saturate the activity of Vpu and inhibit wild-type HIV.

PMID- 21849458
TI  - Human leukocyte antigen genotype and risk of HIV disease progression before and
      after initiation of antiretroviral therapy.
AB  - While the human leukocyte antigen (HLA) genotype has been associated with the
      rate of HIV disease progression in untreated patients, little is known regarding
      these relationships in patients using highly active antiretroviral therapy
      (HAART). The limited data reported to date identified few HLA-HIV disease
      associations in patients using HAART and even occasional associations that were
      opposite of those found in untreated patients. We conducted high-resolution HLA
      class I and II genotyping in a random sample (n = 860) of HIV-seropositive women
      enrolled in a long-term cohort initiated in 1994. HLA-HIV disease associations
      before and after initiation of HAART were examined using multivariate analyses.
      In untreated HIV-seropositive patients, we observed many of the predicted
      associations, consistent with prior studies. For example, HLA-B*57 (beta = -0.7;
      95% confidence interval [CI] = -0.9 to -0.5; P = 5 * 10-11) and Bw4 (beta = -0.2;
      95% CI = -0.4 to -0.1; P = 0.009) were inversely associated with baseline HIV
      viral load, and B*57 was associated with a low risk of rapid CD4+ decline (odds
      ratio [OR] = 0.2; 95% CI = 0.1 to 0.6; P = 0.002). Conversely, in treated
      patients, the odds of a virological response to HAART were lower for B*57:01 (OR
      = 0.2; 95% CI = 0.0 to 0.9; P = 0.03), and Bw4 (OR = 0.4; 95% CI = 0.1 to 1.0; P
      = 0.04) was associated with low odds of an immunological response. The
      associations of HLA genotype with HIV disease are different and sometimes even
      opposite in treated and untreated patients.

PMID- 21849460
TI  - The avian influenza virus NS1 ESEV PDZ binding motif associates with Dlg1 and
      Scribble to disrupt cellular tight junctions.
AB  - The influenza A virus NS1 protein contains a conserved 4-amino-acid-residue PDZ
      ligand binding motif (PBM) at the carboxyl terminus that can function as a
      virulence determinant by targeting cellular PDZ proteins. The NS1 proteins from
      avian and human viral isolates have consensus PBM sequences ESEV and RSKV,
      respectively. Currently circulating highly pathogenic H5N1 viruses contain the
      ESEV PBM which specifically associates with the PDZ proteins Scribble, Dlg1, MAGI
      1, MAGI-2, and MAGI-3. In this study, we found NS1 proteins from viral isolates
      that contain the PBM sequence RSKV, KSEV, or EPEV are unable to associate with
      these PDZ proteins. Other results showed that the ESEV PBM mediates an indirect
      association with PDZ protein, Lin7C, via an interaction with Dlg1. Infection with
      a virus that expresses a NS1 protein with the ESEV PBM results in colocalization
      of NS1, Scribble, and Dlg1 within perinuclear puncta and mislocalization of
      plasma membrane-associated Lin7C to the cytoplasm. Infection of polarized MDCK
      cells with the ESEV virus additionally results in functional disruption of the
      tight junction (TJ) as measured by altered localization of TJ markers ZO-1 and
      Occludin, decreased transepithelial electrical resistance, and increased
      fluorescein isothiocyanate (FITC)-inulin diffusion across the polarized cell
      monolayer. A similar effect on the TJ was observed in MDCK cells depleted for
      either Scribble or Dlg1 by small interfering RNA (siRNA). These findings indicate
      that ESEV PBM-mediated binding of NS1 to Scribble and Dlg1 functions to disrupt
      the cellular TJ and that this effect likely contributes to the severe disease
      associated with highly pathogenic H5N1 influenza A viruses.

PMID- 21849459
TI  - Inactivated or live-attenuated bivalent vaccines that confer protection against
      rabies and Ebola viruses.
AB  - The search for a safe and efficacious vaccine for Ebola virus continues, as no
      current vaccine candidate is nearing licensure. We have developed (i) replication
      competent, (ii) replication-deficient, and (iii) chemically inactivated rabies
      virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a
      reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is
      efficiently expressed by these vaccine candidates and is incorporated into
      virions. The vaccine candidates were avirulent after inoculation of adult mice,
      and viruses with a deletion in the RABV glycoprotein had greatly reduced
      neurovirulence after intracerebral inoculation in suckling mice. Immunization
      with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral
      immunity against each virus and conferred protection from both lethal RABV and
      EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have
      several distinct advantages that may speed the development of inactivated
      vaccines for use in humans and potentially live or inactivated vaccines for use
      in nonhuman primates at risk of EBOV infection in endemic areas.

PMID- 21849461
TI  - The role of the blood-brain barrier during Venezuelan equine encephalitis virus
      infection.
AB  - Venezuelan equine encephalitis (VEE) virus is a mosquito-borne alphavirus
      associated with sporadic outbreaks in human and equid populations in the Western
      Hemisphere. After the bite of an infected mosquito, the virus initiates a
      biphasic disease: a peripheral phase with viral replication in lymphoid and
      myeloid tissues, followed by a neurotropic phase with infection of central
      nervous system (CNS) neurons, causing neuropathology and in some cases fatal
      encephalitis. The mechanisms allowing VEE virus to enter the CNS are currently
      poorly understood. Previous data have shown that the virus gains access to the
      CNS by infecting olfactory sensory neurons in the nasal mucosa of mice. However,
      at day 5 after inoculation, the infection of the brain is multifocal, indicating
      that virus particles are able to cross the blood-brain barrier (BBB). To better
      understand the role of the BBB during VEE virus infection, we used a well
      characterized mouse model system. Using VEE virus replicon particles (VRP), we
      modeled the early events of neuroinvasion, showing that the replication of VRP in
      the nasal mucosa induced the opening of the BBB, allowing peripherally
      administered VRP to invade the brain. Peripheral VEE virus infection was
      characterized by a biphasic opening of the BBB. Further, inhibition of BBB
      opening resulted in a delayed viral neuroinvasion and pathogenesis. Overall,
      these results suggest that VEE virus initially enters the CNS through the
      olfactory pathways and initiates viral replication in the brain, which induces
      the opening of the BBB, allowing a second wave of invading virus from the
      periphery to enter the brain.

PMID- 21849462
TI  - Encephalomyocarditis virus 2A protein is required for viral pathogenesis and
      inhibition of apoptosis.
AB  - The encephalomyocarditis virus (EMCV), a Picornaviridae virus, has a wide host
      spectrum and can cause various diseases. EMCV virulence factors, however, are as
      yet ill defined. Here, we demonstrate that the EMCV 2A protein is essential for
      the pathogenesis of EMCV. Infection of mice with the B279/95 strain of EMCV
      resulted in acute fatal disease, while the clone C9, derived by serial in vitro
      passage of the B279/95 strain, was avirulent. C9 harbored a large deletion in the
      gene encoding the 2A protein. This deletion was incorporated into the cDNA of a
      pathogenic EMCV1.26 strain. The new virus, EMCV1.26Delta2A, was capable of
      replicating in vitro, albeit more slowly than EMCV1.26. Only mice inoculated with
      EMCV1.26 triggered death within a few days. Mice infected with EMCV1.26Delta2A
      did not exhibit clinical signs, and histopathological analyses showed no damage
      in the central nervous system, unlike EMCV1.26-infected mice. In vitro,
      EMCV1.26Delta2A presented a defect in viral particle release correlating with
      prolonged cell viability. Unlike EMCV1.26, which induced cytopathic cell death,
      EMCV1.26Delta2A induced apoptosis via caspase 3 activation. This strongly
      suggests that the 2A protein is required for inhibition of apoptosis during EMCV
      infection. All together, our data indicate that the EMCV 2A protein is important
      for the virus in counteracting host defenses, since Delta2A viruses were no
      longer pathogenic and were unable to inhibit apoptosis in vitro.

PMID- 21849463
TI  - A cluster of basic amino acids in the factor X serine protease mediates surface
      attachment of adenovirus/FX complexes.
AB  - Hepatocyte transduction following intravenous administration of adenovirus 5
      (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon.
      The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes
      through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the
      critical HSPG-interacting residues of FX. We generated an FX mutant by modifying
      seven residues in the SP domain. Surface plasmon resonance demonstrated that
      mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell
      binding and transduction were abolished. A cluster of basic amino acids in the SP
      domain therefore mediates surface interaction of the Ad/FX complex.

PMID- 21849464
TI  - A neonatal Fc receptor-targeted mucosal vaccine strategy effectively induces HIV
      1 antigen-specific immunity to genital infection.
AB  - Strategies to prevent the sexual transmission of HIV include vaccines that elicit
      durable, protective mucosal immune responses. A key to effective mucosal immunity
      is the capacity for antigens administered locally to cross epithelial barriers.
      Given the role of neonatal Fc receptor (FcRn) in transferring IgG across
      polarized epithelial cells which line mucosal surfaces, FcRn might be useful for
      delivering HIV vaccine antigens across mucosal epithelial barriers to the
      underlying antigen-presenting cells. Chimeric proteins composed of HIV Gag (p24)
      fused to the Fc region of IgG (Gag-Fc) bind efficiently to airway mucosa and are
      transported across this epithelial surface. Mice immunized intranasally with Gag
      Fc plus CpG adjuvant developed local and systemic immunity, including durable B
      and T cell memory. Gag-specific immunity was sufficiently potent to protect
      against an intravaginal challenge with recombinant vaccinia virus expressing the
      HIV Gag protein. Intranasal administration of a Gag-Fc/CpG vaccine protected at a
      distal mucosal site. Our data suggest that targeting of FcRn with chimeric
      immunogens may be an important strategy for mucosal immunization and should be
      considered a new approach for preventive HIV vaccines.

PMID- 21849465
TI  - Cross-linking of rotavirus outer capsid protein VP7 by antibodies or disulfides
      inhibits viral entry.
AB  - Antibodies that neutralize rotavirus infection target outer coat proteins VP4 and
      VP7 and inhibit viral entry. The structure of a VP7-Fab complex (S. T. Aoki, et
      al., Science 324:1444-1447, 2009) led us to reclassify epitopes into two binding
      regions at inter- and intrasubunit boundaries of the calcium-dependent trimer. It
      further led us to show that antibodies binding at the intersubunit boundary
      inhibit uncoating of the virion outer layer. We have now tested representative
      antibodies for each of the defined structural epitope regions and find that
      antibodies recognizing epitopes in either binding region neutralize by cross
      linking VP7 trimers. Antibodies that bind at the intersubunit junction neutralize
      as monovalent Fabs, while those that bind at the intrasubunit region require
      divalency. The VP7 structure has also allowed us to design a disulfide cross
      linked VP7 mutant which recoats double-layered particles (DLPs) as efficiently as
      does wild-type VP7 but which yields particles defective in cell entry as
      determined both by lack of infectivity and by loss of alpha-sarcin toxicity in
      the presence of recoated particles. We conclude that dissociation of the VP7
      trimer is an essential step in viral penetration into cells.

PMID- 21849466
TI  - Reversion of PB2-627E to -627K during replication of an H5N1 Clade 2.2 virus in
      mammalian hosts depends on the origin of the nucleoprotein.
AB  - H5N1 highly pathogenic avian influenza viruses (HPAIV) of clade 2.2 spread from
      Southeast Asia to Europe. Intriguingly, in contrast to all common avian strains
      specifying glutamic acid at position 627 of the PB2 protein (PB2-627E), they
      carry a lysine at this position (PB2-627K), which is normally found only in human
      strains. To analyze the impact of this mutation on the host range of HPAIV H5N1,
      we altered PB2-627K to PB2-627E in the European isolate A/Swan/Germany/R65/2006
      (R65). In contrast to the parental R65, multicycle growth and polymerase activity
      of the resulting mutant R65-PB2(K627E) were considerably impaired in mammalian
      but not in avian cells. Correspondingly, the 50% lethal dose (LD50) in mice was
      increased by three orders of magnitude, whereas virulence in chicken remained
      unchanged, resulting in 100% lethality, as was found for the parental R65.
      Strikingly, R65-PB2(K627E) reverted to PB2-627K after only one passage in mice
      but did not revert in chickens. To investigate whether additional R65 genes
      influence reversion, we passaged R65-PB2(K627E) reassortants containing genes
      from A/Hong Kong/156/97 (H5N1) (carrying PB2-627E), in avian and mammalian cells.
      Reversion to PB2-627K in mammalian cells required the presence of the R65
      nucleoprotein (NP). This finding corresponds to results of others that during
      replication of avian strains in mammalian cells, PB2-627K restores an impaired
      PB2-NP association. Since this mutation is apparently not detrimental for virus
      prevalence in birds, it has not been eliminated. However, the prompt reversion to
      PB2-627K in MDCK cells and mice suggests that the clade 2.2 H5N1 HPAIV may have
      had a history of intermediate mammalian hosts.

PMID- 21849467
TI  - Newcastle disease virus expressing human immunodeficiency virus type 1 envelope
      glycoprotein induces strong mucosal and serum antibody responses in Guinea pigs.
AB  - Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly through mucosal
      sites. Optimum strategies to elicit both systemic and mucosal immunity are
      critical for the development of vaccines against HIV-1. We therefore sought to
      evaluate the induction of systemic and mucosal immune responses by the use of
      Newcastle disease virus (NDV) as a vaccine vector. We generated a recombinant
      NDV, designated rLaSota/gp160, expressing the gp160 envelope (Env) protein of HIV
      1 from an added gene. The gp160 protein expressed by rLaSota/gp160 virus was
      detected on an infected cell surface and was incorporated into the NDV virion.
      Biochemical studies showed that gp160 present in infected cells and in the virion
      formed a higher-order oligomer that retained recognition by conformationally
      sensitive monoclonal antibodies. Expression of gp160 did not increase the
      virulence of recombinant NDV (rNDV) strain LaSota. Guinea pigs were administered
      rLaSota/gp160 via the intranasal (i.n.) or intramuscular (i.m.) route in
      different prime-boost combinations. Systemic and mucosal antibody responses
      specific to the HIV-1 envelope protein were assessed in serum and vaginal washes,
      respectively. Two or three immunizations via the i.n. or i.m. route induced a
      more potent systemic and mucosal immune response than a single immunization by
      either route. Priming by the i.n. route was more immunogenic than by the i.m.
      route, and the same was true for the boosts. Furthermore, immunization with
      rLaSota/gp160 by any route or combination of routes induced a Th1-type response,
      as reflected by the induction of stronger antigen-specific IgG2a than IgG1
      antibody responses. Additionally, i.n. immunization elicited a stronger
      neutralizing serum antibody response to laboratory-adapted HIV-1 strain MN.3.
      These data illustrate that it is feasible to use NDV as a vaccine vector to
      elicit potent humoral and mucosal responses to the HIV-1 envelope protein.

PMID- 21849468
TI  - Evidence of a role for antizyme and antizyme inhibitor as regulators of human
      cancer.
AB  - Antizyme and its endogenous antizyme inhibitor have recently emerged as prominent
      regulators of cell growth, transformation, centrosome duplication, and
      tumorigenesis. Antizyme was originally isolated as a negative modulator of the
      enzyme ornithine decarboxylase (ODC), an essential component of the polyamine
      biosynthetic pathway. Antizyme binds ODC and facilitates proteasomal ODC
      degradation. Antizyme also facilitates degradation of a set of cell cycle
      regulatory proteins, including cyclin D1, Smad1, and Aurora A kinase, as well as
      Mps1, a protein that regulates centrosome duplication. Antizyme has been reported
      to function as a tumor suppressor and to negatively regulate tumor cell
      proliferation and transformation. Antizyme inhibitor binds to antizyme and
      suppresses its known functions, leading to increased polyamine synthesis,
      increased cell proliferation, and increased transformation and tumorigenesis.
      Gene array studies show antizyme inhibitor to be amplified in cancers of the
      ovary, breast, and prostate. In this review, we summarize the current literature
      on the role of antizyme and antizyme inhibitor in cancer, discuss how the ratio
      of antizyme to antizyme inhibitor can influence tumor growth, and suggest
      strategies to target this axis for tumor prevention and treatment.

PMID- 21849469
TI  - Epithelial protein-tyrosine phosphatase 1B contributes to the induction of
      mammary tumors by HER2/Neu but is not essential for tumor maintenance.
AB  - Protein-tyrosine phosphatase 1B (PTP1B), a well-established metabolic regulator,
      plays an important role in breast cancer. Using whole-body PTP1B knockout mice,
      recent studies have shown that PTP1B ablation delays HER2/Neu-induced mammary
      cancer. Whether PTP1B plays a cell-autonomous or a noncell-autonomous role in
      HER2/Neu-evoked tumorigenesis and whether it is involved in tumor maintenance was
      unknown. We generated mice expressing HER2/Neu and lacking PTP1B specifically in
      the mammary epithelium. We found that mammary-specific deletion of PTP1B delays
      the onset of HER2/Neu-evoked mammary tumors, establishing a cell autonomous role
      for PTP1B in such neoplasms. We also deleted PTP1B in established mouse mammary
      tumors or depleted PTP1B in human breast cancer cell lines grown as xenografts.
      PTP1B inhibition did not affect tumor growth in either model showing that neither
      epithelial nor stromal PTP1B is necessary for tumor maintenance. Taken together,
      our data show that despite the PTP1B contribution to tumor onset, it is not
      essential for tumor maintenance. This suggests that PTP1B inhibition could be
      effective in breast tumor prevention.

PMID- 21849470
TI  - Causal link between microsatellite instability and hMRE11 dysfunction in human
      cancers.
AB  - Maintenance of genomic integrity is essential for cell survival, and genomic
      instability is a commonly recognized intrinsic property of all cancers.
      Microsatellite instability (MSI) represents a frequently occurring and easily
      traceable simple form of sequence variation, signified by the contraction or
      expansion of specific DNA sequences containing short tandem repeats. MSI is
      frequently detected in tumor cells with DNA mismatch repair (MMR) deficiency. It
      is commonly conceived that instability at individual microsatellite loci can
      arise spontaneously in cells independent of MMR status, and different
      microsatellite loci are generally not affected uniformly by MMR deficiency. It is
      well recognized that MMR deficiency per se is not sufficient to initiate
      tumorigenesis; rather, the biological effects have to be exerted by mutations in
      genes controlling cell survival, DNA damage response, and apoptosis. Recently,
      shortening of an intronic hMRE11 poly(T)11 tract has been associated with MMR
      deficiency, raising the possibility that hMRE11 may be inactivated by defective
      MMR. However, the molecular nature underlying this association is presently
      unknown, and review of the current literature suggests that hMRE11 is most likely
      involved with the MMR pathway in a more complex fashion than simply being a MMR
      target gene. An alternative scenario is proposed to better reconcile the
      differences among various studies. The potential role of hMRE11 in telomere
      repeats stability is also discussed.

PMID- 21849471
TI  - Oxidative stress and prostate cancer progression are elicited by membrane-type 1
      matrix metalloproteinase.
AB  - Oxidative stress caused by high levels of reactive oxygen species (ROS) has been
      correlated with prostate cancer aggressiveness. Expression of membrane-type 1
      matrix metalloproteinase (MT1-MMP), which has been implicated in cancer invasion
      and metastasis, is associated with advanced prostate cancer. We show here that
      MT1-MMP plays a key role in eliciting oxidative stress in prostate cancer cells.
      Stable MT1-MMP expression in less invasive LNCaP prostate cancer cells with low
      endogenous MT1-MMP increased activity of ROS, whereas MT1-MMP knockdown in DU145
      cells with high endogenous MT1-MMP decreased activity of ROS. Expression of MT1
      MMP increased oxidative DNA damage in LNCaP and in DU145 cells, indicating that
      MT1-MMP-mediated induction of ROS caused oxidative stress. MT1-MMP expression
      promoted a more aggressive phenotype in LNCaP cells that was dependent on
      elaboration of ROS. Blocking ROS activity using the ROS scavenger N
      acetylcysteine abrogated MT1-MMP-mediated increase in cell migration and
      invasion. MT1-MMP-expressing LNCaP cells displayed an enhanced ability to grow in
      soft agar that required increased ROS. Using cells expressing MT1-MMP mutant
      cDNAs, we showed that ROS activation entails cell surface MT1-MMP proteolytic
      activity. Induction of ROS in prostate cancer cells expressing MT1-MMP required
      adhesion to extracellular matrix proteins and was impeded by anti-beta1 integrin
      antibodies. These results highlight a novel mechanism of malignant progression in
      prostate cancer cells that involves beta1 integrin-mediated adhesion, in concert
      with MT1-MMP proteolytic activity, to elicit oxidative stress and induction of a
      more invasive phenotype.

PMID- 21849472
TI  - Retrolinkin cooperates with endophilin A1 to mediate BDNF-TrkB early endocytic
      trafficking and signaling from early endosomes.
AB  - Brain-derived neurotrophic factor (BDNF) binds to its cell surface receptor TrkB
      to regulate differentiation, development, synaptic plasticity, and functional
      maintenance of neuronal cells. Binding of BDNF triggers TrkB dimerization and
      autophosphorylation, which provides docking sites for adaptor proteins to recruit
      and activate downstream signaling molecules. The molecular mechanisms underlying
      BDNF-TrkB endocytic trafficking crucial for spatiotemporal control of signaling
      pathways remain to be elucidated. Here we show that retrolinkin, a transmembrane
      protein, interacts with endophilin A1 and mediates BDNF-activated TrkB (pTrk)
      trafficking and signaling in CNS neurons. We find that activated TrkB colocalizes
      and interacts with the early endosome marker APPL1. Both retrolinkin and
      endophilin A1 are required for BDNF-induced dendrite development and acute
      extracellular signal-regulated kinase activation from early endosomes.
      Suppression of retrolinkin expression not only blocks BDNF-triggered TrkB
      internalization, but also prevents recruitment of endophilin A1 to pTrk vesicles
      trafficking through APPL1-positive endosomes. These findings reveal a novel
      mechanism for BDNF-TrkB to regulate signaling both in time and space through a
      specific membrane trafficking pathway.

PMID- 21849473
TI  - Citron kinase controls abscission through RhoA and anillin.
AB  - The small GTPase RhoA plays a crucial role in the different stages of
      cytokinesis, including contractile ring formation, cleavage furrow ingression,
      and midbody abscission. Citron kinase (CIT-K), a protein required for cytokinesis
      and conserved from insects to mammals, is currently considered a cytokinesis
      specific effector of active RhoA. In agreement with previous observations, we
      show here that, as in Drosophila cells, CIT-K is specifically required for
      abscission in mammalian cells. However, in contrast with the current view, we
      provide evidence that CIT-K is an upstream regulator rather than a downstream
      effector of RhoA during late cytokinesis. In addition, we show that CIT-K is
      capable of physically and functionally interacting with the actin-binding protein
      anillin. Active RhoA and anillin are displaced from the midbody in CIT-K-depleted
      cells, while only anillin, but not CIT-K, is affected if RhoA is inactivated in
      late cytokinesis. The overexpression of CIT-K and of anillin leads to abscission
      delay. However, the delay produced by CIT-K overexpression can be reversed by
      RhoA inactivation, while the delay produced by anillin overexpression is RhoA
      independent. Altogether, these results indicate that CIT-K is a crucial
      abscission regulator that may promote midbody stability through active RhoA and
      anillin.

PMID- 21849474
TI  - Spatial control of Cdc42 activation determines cell width in fission yeast.
AB  - The fission yeast Schizosaccharomyces pombe is a rod-shaped cell that grows by
      linear extension at the cell tips, with a nearly constant width throughout the
      cell cycle. This simple geometry makes it an ideal system for studying the
      control of cellular dimensions. In this study, we carried out a near-genome-wide
      screen for mutants wider than wild-type cells. We found 11 deletion mutants that
      were wider; seven of the deleted genes are implicated in the control of the small
      GTPase Cdc42, including the Cdc42 guanine nucleotide exchange factor (GEF) Scd1
      and the Cdc42 GTPase-activating protein (GAP) Rga4. Deletions of rga4 and scd1
      had additive effects on cell width, and the proteins localized independently of
      one another, with Rga4 located at the cell sides and Scd1 at the cell tips.
      Activated Cdc42 localization is altered in rga4Delta, scd1Delta, and scd2Delta
      mutants. Delocalization and ectopic retargeting experiments showed that the
      localizations of Rga4 and Scd1 are crucial for their roles in determining cell
      width. We propose that the GAP Rga4 and the GEF Scd1 establish a gradient of
      activated Cdc42 within the cellular tip plasma membrane, and it is this gradient
      that determines cell growth-zone size and normal cell width.

PMID- 21849475
TI  - Clathrin light chain directs endocytosis by influencing the binding of the yeast
      Hip1R homologue, Sla2, to F-actin.
AB  - The role of clathrin light chain (CLC) in clathrin-mediated endocytosis is not
      completely understood. Previous studies showed that the CLC N-terminus (CLC-NT)
      binds the Hip1/Hip1R/Sla2 family of membrane/actin-binding factors and that
      overexpression of the CLC-NT in yeast suppresses endocytic defects of clathrin
      heavy-chain mutants. To elucidate the mechanistic basis for this suppression, we
      performed synthetic genetic array analysis with a clathrin CLC-NT deletion
      mutation (clc1-Delta19-76). clc1-Delta19-76 suppressed the internalization
      defects of null mutations in three late endocytic factors: amphiphysins (rvs161
      and rvs167) and verprolin (vrp1). In actin sedimentation assays, CLC binding to
      Sla2 inhibited Sla2 interaction with F-actin. Furthermore, clc1-Delta19-76
      suppression of the rvs and vrp phenotypes required the Sla2 actin-binding talin
      Hip1/R/Sla2 actin-tethering C-terminal homology domain, suggesting that clc1
      Delta19-76 promotes internalization by prolonging actin engagement by Sla2. We
      propose that CLC directs endocytic progression by pruning the Sla2-actin
      attachments in the clathrin lattice, providing direction for membrane
      internalization.

PMID- 21849476
TI  - A phosphatase threshold sets the level of Cdk1 activity in early mitosis in
      budding yeast.
AB  - Entry into mitosis is initiated by synthesis of cyclins, which bind and activate
      cyclin-dependent kinase 1 (Cdk1). Cyclin synthesis is gradual, yet activation of
      Cdk1 occurs in a stepwise manner: a low level of Cdk1 activity is initially
      generated that triggers early mitotic events, which is followed by full
      activation of Cdk1. Little is known about how stepwise activation of Cdk1 is
      achieved. A key regulator of Cdk1 is the Wee1 kinase, which phosphorylates and
      inhibits Cdk1. Wee1 and Cdk1 show mutual regulation: Cdk1 phosphorylates Wee1,
      which activates Wee1 to inhibit Cdk1. Further phosphorylation events inactivate
      Wee1. We discovered that a specific form of protein phosphatase 2A (PP2A(Cdc55))
      opposes the initial phosphorylation of Wee1 by Cdk1. In vivo analysis, in vitro
      reconstitution, and mathematical modeling suggest that PP2A(Cdc55) sets a
      threshold that limits activation of Wee1, thereby allowing a low constant level
      of Cdk1 activity to escape Wee1 inhibition in early mitosis. These results define
      a new role for PP2A(Cdc55) and reveal a systems-level mechanism by which
      dynamically opposed kinase and phosphatase activities can modulate signal
      strength.

PMID- 21849477
TI  - Rab22 controls NGF signaling and neurite outgrowth in PC12 cells.
AB  - Rab22 is a small GTPase that is localized on early endosomes and regulates early
      endosomal sorting. This study reports that Rab22 promotes nerve growth factor
      (NGF) signaling-dependent neurite outgrowth and gene expression in PC12 cells by
      sorting NGF and the activated/phosphorylated receptor (pTrkA) into signaling
      endosomes to sustain signal transduction in the cell. NGF binding induces the
      endocytosis of pTrkA into Rab22-containing endosomes. Knockdown of Rab22 via
      small hairpin RNA (shRNA) blocks NGF-induced pTrkA endocytosis into the endosomes
      and gene expression (VGF) and neurite outgrowth. Overexpression of human Rab22
      can rescue the inhibitory effects of the Rab22 shRNA, suggesting a specific Rab22
      function in NGF signal transduction, rather than off-target effects. Furthermore,
      the Rab22 effector, Rabex-5, is necessary for NGF-induced neurite outgrowth and
      gene expression, as evidenced by the inhibitory effect of shRNA-mediated
      knockdown of Rabex-5. Disruption of the Rab22-Rabex-5 interaction via
      overexpression of the Rab22-binding domain of Rabex-5 in the cell also blocks NGF
      induced neurite outgrowth, suggesting a critical role of Rab22-Rabex-5
      interaction in the biogenesis of NGF-signaling endosomes to sustain the signal
      for neurite outgrowth. These data provide the first evidence for an early
      endosomal Rab GTPase as a positive regulator of NGF signal transduction and cell
      differentiation.

PMID- 21849479
TI  - Increased risk of venous thrombosis in persons with clinically diagnosed
      superficial vein thrombosis: results from the MEGA study.
AB  - Superficial vein thrombosis (SVT) is regarded a self-limiting disorder, although
      the authors of recent studies showed that ultrasonographically diagnosed SVT is a
      precursor for venous thrombosis. We aimed to determine whether the same holds
      true for clinically diagnosed SVT and to what extent it is associated with
      thrombophilia in a population-based case-control study (ie, Multiple
      Environmental and Genetic Assessment of risk factors for venous thrombosis). We
      found that a history of clinical SVT was associated with a 6.3-fold (95%
      confidence interval [CI] 5.0-8.0) increased risk of deep-vein thrombosis and a
      3.9-fold (95% CI 3.0-5.1) increased risk of pulmonary embolism. Blood group non-O
      and factor V Leiden showed a small increase in SVT risk in controls, with odds
      ratios of 1.3 (95% CI 0.9-2.0) and 1.5 (95% CI 0.7-3.3), respectively. In
      conclusion, clinically diagnosed SVT was a risk factor for venous thrombosis.
      Given that thrombophilia was only weakly associated with SVT, it is likely that
      other factors (varicosis, obesity, stasis) also play a role in its etiology.

PMID- 21849478
TI  - The activation of ezrin-radixin-moesin proteins is regulated by netrin-1 through
      Src kinase and RhoA/Rho kinase activities and mediates netrin-1-induced axon
      outgrowth.
AB  - The receptor Deleted in Colorectal Cancer (DCC) mediates the attractive response
      of axons to the guidance cue netrin-1 during development. On netrin-1
      stimulation, DCC is phosphorylated and induces the assembly of signaling
      complexes within the growth cone, leading to activation of cytoskeleton
      regulators, namely the GTPases Rac1 and Cdc42. The molecular mechanisms that link
      netrin-1/DCC to the actin machinery remain unclear. In this study we seek to
      demonstrate that the actin-binding proteins ezrin-radixin-moesin (ERM) are
      effectors of netrin-1/DCC signaling in embryonic cortical neurons. We show that
      ezrin associates with DCC in a netrin-1-dependent manner. We demonstrate that
      netrin-1/DCC induces ERM phosphorylation and activation and that the
      phosphorylation of DCC is required in that context. Moreover, Src kinases and
      RhoA/Rho kinase activities mediate netrin-1-induced ERM phosphorylation in
      neurons. We also observed that phosphorylated ERM proteins accumulate in growth
      cone filopodia, where they colocalize with DCC upon netrin-1 stimulation.
      Finally, we show that loss of ezrin expression in cortical neurons significantly
      decreases axon outgrowth induced by netrin-1. Together, our findings demonstrate
      that netrin-1 induces the formation of an activated ERM/DCC complex in growth
      cone filopodia, which is required for netrin-1-dependent cortical axon outgrowth.

PMID- 21849480
TI  - Activated protein C inhibits high mobility group box 1 signaling in endothelial
      cells.
AB  - A pathogenic role for high-mobility group box 1 (HMGB1) protein has been
      postulated in severe sepsis. Activated protein C (APC) is the only drug approved
      by the Food and Drug Administration for severe sepsis; however, its effect on
      HMGB1 signaling has never been investigated. Here, we monitored the effect of APC
      on the lipopolysaccharide-mediated release of HMGB1 and the HMGB1-mediated
      modulation of proinflammatory responses in HUVECs. APC potently inhibited the
      release of HMGB1 and down-regulated the adhesion of the monocytic cell line, THP
      1, to HMGB1-activated endothelial cells. HMGB1 up-regulated proinflammatory
      responses by interacting with 3 pathogen-related pattern recognition receptors:
      TLR2 and TLR4 and the receptor for advanced glycation end products. APC not only
      inhibited HMGB1 release but also down-regulated the cell surface expression of
      all 3 HMGB1 receptors in endothelial cells. The protective effects of APC were
      mediated through endothelial cell protein C receptor (EPCR) and protease
      activated receptor 1 (PAR-1). Interestingly, a thrombin derivative containing the
      Gla-domain of APC recapitulated all protective effects of APC with a 20- to 50
      fold higher efficacy. These results suggest that the EPCR- and PAR-1-dependent
      protective effects of APC in severe sepsis may partially be mediated through the
      inhibition of HMGB1 signaling and that the chimeric thrombin mutant has potential
      therapeutic utility for severe sepsis.

PMID- 21849481
TI  - Natural history of transient myeloproliferative disorder clinically diagnosed in
      Down syndrome neonates: a report from the Children's Oncology Group Study A2971.
AB  - Transient myeloproliferative disorder (TMD), restricted to newborns with trisomy
      21, is a megakaryocytic leukemia that although lethal in some is distinguished by
      its spontaneous resolution. Later development of acute myeloid leukemia (AML)
      occurs in some. Prospective enrollment (n = 135) elucidated the natural history
      in Down syndrome (DS) patients diagnosed with TMD via the use of uniform
      monitoring and intervention guidelines. Prevalent at diagnosis were leukocytosis,
      peripheral blast exceeding marrow blast percentage, and hepatomegaly. Among those
      with life-threatening symptoms, most (n = 29/38; 76%) received intervention
      therapy until symptoms abated and then were monitored similarly. Organomegaly
      with cardiopulmonary compromise most frequently led to intervention (43%). Death
      occurred in 21% but only 10% were attributable to TMD (intervention vs
      observation patients: 13/14 vs 1/15 because of TMD). Among those solely observed,
      peripheral blasts and all other TMD symptoms cleared at a median of 36 and 49
      days from diagnosis, respectively. On the basis of the diagnostic clinical
      findings of hepatomegaly with or without life-threatening symptoms, 3 groups were
      identified with differing survival: low risk with neither finding (38%),
      intermediate risk with hepatomegaly alone (40%), and high risk with both (21%;
      overall survival: 92% +/- 8%, 77% +/- 12%, and 51% +/- 19%, respectively; P <=
      .001). Among all, AML subsequently occurred in 16% at a median of 441 days
      (range, 118-1085 days). The trial is registered at http://www.clinicaltrials.gov
      as NCT00003593.

PMID- 21849483
TI  - A blood flow-dependent klf2a-NO signaling cascade is required for stabilization
      of hematopoietic stem cell programming in zebrafish embryos.
AB  - Blood flow has long been thought to be important for vessel development and
      function, but its role in HSC development is not yet fully understood. Here, we
      take advantage of zebrafish embryos with circulation defects that retain
      relatively normal early development to illustrate the combinatorial roles of
      genetic and hemodynamic forces in HSC development. We show that blood flow is not
      required for initiation of HSC gene expression, but instead is indispensable for
      its maintenance. Knockdown of klf2a mimics the silent heart (sih/tnnt2a)
      phenotype while overexpression of klf2a in tnnt2a morphant embryos can rescue HSC
      defects, suggesting that klf2a is a downstream mediator of blood flow.
      Furthermore, the expression of NO synthase (nos) was reduced in klf2a knockdown
      embryos, and ChIP analysis showed that endogenous Klf2a is bound to the promoters
      of nos genes in vivo, indicating direct gene regulation. Finally, administration
      of the NO agonist S-nitroso N-acetylpenicillamine (SNAP) can restore HSC
      development in tnnt2a and klf2a morphants, suggesting that NO signaling is
      downstream of Klf2a which is induced by hemodynamic forces. Taken together, we
      have demonstrated that blood flow is essential for HSC development and is
      mediated by a klf2a-NO signaling cascade in zebrafish.

PMID- 21849482
TI  - Endoplasmic reticulum stress causes EBV lytic replication.
AB  - Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in
      mammalian cells to ensure efficient folding, sorting, and processing of client
      proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to
      the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in
      the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late
      (gp350) genes, gp350 surface expression, and virus release. The protein
      phosphatase 1 a (PP1a)-specific phosphatase inhibitor Salubrinal (SAL) synergized
      with TG to induce EBV lytic genes; however, TG treatment alone was sufficient to
      activate EBV lytic replication. SAL showed ER-stress-dependent and -independent
      antiviral effects, preventing virus release in human LCLs and abrogating gp350
      expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B95-8 cells. TG
      resulted in sustained BCL6 but not BLIMP1 or CD138 expression, which is
      consistent with maintenance of a germinal center B-cell, rather than plasma-cell,
      phenotype. Microarray analysis identified candidate genes governing lytic
      replication in LCLs undergoing ER stress.

PMID- 21849484
TI  - Serglycin participates in retention of alpha-defensin in granules during
      myelopoiesis.
AB  - The mechanism by which proteins are targeted to neutrophil granules is largely
      unknown. The intracellular proteoglycan serglycin has been shown to have
      important functions related to storage of proteins in several types of granules.
      The possible role of serglycin in the localization of the alpha-defensin, human
      neutrophil peptide 1 (HNP-1), a major azurophil granule protein in human
      neutrophils, was investigated. Murine myeloid cells, stably transfected to
      express HNP-1, were capable of processing HNP-1, and HNP-1 was found to associate
      with serglycin in murine and human myeloid cell lines as well as in human bone
      marow cells. A transgenic mouse expressing HNP-1 in the myeloid compartment was
      crossed with mice deficient in serglycin or neutrophil elastase to investigate
      HNP-1 sorting and processing. Neither deficiency affected processing of HNP-1,
      but the ability to retain fully processed HNP-1 intracellularly was reduced in
      mice that lack serglycin. Human granulocyte precursors transfected with siRNA
      against serglycin displayed similar reduced capability to retain fully processed
      HNP-1, demonstrating a role of serglycin in retaining mature HNP-1
      intracellularly, thus preventing potential toxic effects of extracellular HNP-1.

PMID- 21849485
TI  - Changes in the dynamics of the excess mortality rate in chronic phase-chronic
      myeloid leukemia over 1990-2007: a population study.
AB  - Imatinib has transformed the prognosis and the management of chronic myeloid
      leukemia (CML) and has probably changed the patterns of mortality rates. We
      explored this change at each disease severity level (Sokal score) through a
      flexible statistical modeling of the effect of the year of diagnosis on the
      excess mortality rate. The study included 691 chronic-phase patients from Nord
      Pas-de-Calais French CML registry diagnosed from 1990 to 2007. Imatinib was given
      to 93% of the patients diagnosed after 2000. Comparing the 1990-1994, 1995-1999,
      and 2000-2007 periods of diagnosis, the 5-year relative survival improved from
      64% to 66% and 88%. The year of diagnosis was associated with a significant
      reduction of the excess mortality, but only in patients with intermediate to high
      Sokal scores. In high-risk patients diagnosed in the early 1990s, a peak of
      excess mortality was observed during the second year of follow-up. That peak
      decreased progressively over the years of diagnosis until disappearing in
      patients diagnosed after 2000. This study showed different effects according to
      Sokal scores of the use of imatinib on mortality in patients with chronic-phase
      CML and showed that since 2000 the pattern of mortality of high-risk patients
      became similar to that of intermediate-risk ones.

PMID- 21849487
TI  - Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus
      dexamethasone as induction treatment before autologous stem cell transplantation
      in newly diagnosed multiple myeloma.
AB  - The Intergroupe Francophone du Myelome conducted a randomized trial to compare
      bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and
      autologous stem cell transplantation (ASCT) to a combination consisting of
      reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients
      with multiple myeloma. Overall, a total of 199 patients were centrally randomly
      assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate
      was the same in both groups (13% in the vtD arm, 12% in the VD arm, P = .74).
      However, the CR plus very good partial response (VGPR) rate was significantly
      higher in the vtD arm (49% vs 36%, P = .05). After ASCT, the CR plus VGPR rate
      was significantly higher in the vtD arm (74% vs 58%, P = .02). The reduced doses
      of bortezomib and thalidomide translated into a reduced incidence of peripheral
      neuropathy (PN): grade >= 2 PN were reported in 34% in the VD arm versus 14% in
      the vtD arm (P = .001). vtD, including reduced doses of bortezomib and
      thalidomide, yields higher VGPR rates compared with VD and can be considered a
      new effective triplet combination before HDT/ASCT.

PMID- 21849486
TI  - Safety and persistence of adoptively transferred autologous CD19-targeted T cells
      in patients with relapsed or chemotherapy refractory B-cell leukemias.
AB  - We report the findings from the first 10 patients with chemotherapy-refractory
      chronic lymphocytic leukemia (CLL) or relapsed B-cell acute lymphoblastic
      leukemia (ALL) we have enrolled for treatment with autologous T cells modified to
      express 19-28z, a second-generation chimeric antigen (Ag) receptor specific to
      the B-cell lineage Ag CD19. Eight of the 9 treated patients tolerated 19-28z(+) T
      cell infusions well. Three of 4 evaluable patients with bulky CLL who received
      prior conditioning with cyclophosphamide exhibited either a significant reduction
      or a mixed response in lymphadenopathy without concomitant development of B-cell
      aplasia. In contrast, one patient with relapsed ALL who was treated in remission
      with a similar T-cell dose developed a predicted B-cell aplasia. The short-term
      persistence of infused T cells was enhanced by prior cyclophosphamide
      administration and inversely proportional to the peripheral blood tumor burden.
      Further analyses showed rapid trafficking of modified T cells to tumor and
      retained ex vivo cytotoxic potential of CD19-targeted T cells retrieved 8 days
      after infusion. We conclude that this adoptive T-cell approach is promising and
      more likely to show clinical benefit in the setting of prior conditioning
      chemotherapy and low tumor burden or minimal residual disease. These studies are
      registered at www.clinicaltrials.org as #NCT00466531 (CLL protocol) and
      #NCT01044069 (B-ALL protocol).

PMID- 21849488
TI  - Role of thin descending limb urea transport in renal urea handling and the urine
      concentrating mechanism.
AB  - Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending
      limb of Henle's loop and in descending vasa recta, respectively. To study their
      role and possible interaction in the context of the urine concentration
      mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was
      generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with
      UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B
      transcripts and proteins and showed normal survival and growth. Daily urine
      output was significantly higher in UT-A2/B knockout mice than that in wild-type
      mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B
      knockout mice was intermediate between that in UT-B knockout and wild-type mice.
      The changes in urine osmolality and flow rate, plasma and urine urea
      concentration, as well as non-urea solute concentration after an acute urea load
      or chronic changes in protein intake suggested that UT-A2 plays a role in the
      progressive accumulation of urea in the inner medulla. These results suggest that
      in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin
      descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B
      knockout mice partially remedies the urine concentrating defect caused by UT-B
      deletion, by reducing urea loss from the descending limbs to the peripheral
      circulation; instead, urea is returned to the inner medulla through the loops of
      Henle and the collecting ducts.

PMID- 21849489
TI  - Potassium deprivation: a systems approach.

PMID- 21849490
TI  - Preactivation of AMPK by metformin may ameliorate the epithelial cell damage
      caused by renal ischemia.
AB  - Alterations in epithelial cell polarity and in the subcellular distributions of
      epithelial ion transport proteins are key molecular consequences of acute kidney
      injury and intracellular energy depletion. AMP-activated protein kinase (AMPK), a
      cellular energy sensor, is rapidly activated in response to renal ischemia, and
      we demonstrate that its activity is upregulated by energy depletion in Madin
      Darby canine kidney (MDCK) cells. We hypothesized that AMPK activity may
      influence the maintenance or recovery of epithelial cell organization in
      mammalian renal epithelial cells subjected to energy depletion. MDCK cells were
      ATP depleted through a 1-h incubation with antimycin A and 2-deoxyglucose.
      Immunofluoresence localization demonstrated that this regimen induces
      mislocalization of the Na-K-ATPase from its normal residence at the basolateral
      plasma membrane to intracellular vesicular compartments. When cells were
      pretreated with the AMPK activator metformin before energy depletion, basolateral
      localization of Na-K-ATPase was preserved. In MDCK cells in which AMPK expression
      was stably knocked down with short hairpin RNA, preactivation of AMPK with
      metformin did not prevent Na-K-ATPase redistribution in response to energy
      depletion. In vivo studies demonstrate that metformin activated renal AMPK and
      that treatment with metformin before renal ischemia preserved cellular integrity,
      preserved Na-K-ATPase localization, and led to reduced levels of neutrophil
      gelatinase-associated lipocalin, a biomarker of tubular injury. Thus AMPK may
      play a role in preserving the functional integrity of epithelial plasma membrane
      domains in the face of energy depletion. Furthermore, pretreatment with an AMPK
      activator before ischemia may attenuate the severity of renal tubular injury in
      the context of acute kidney injury.

PMID- 21849491
TI  - Role of AT1 receptor-mediated salt retention in angiotensin II-dependent
      hypertension.
AB  - Activation of type 1 angiotensin II (AT(1)) receptors in the kidney promotes
      blood pressure elevation and target organ damage, but whether renal AT(1)
      receptors influence the level of hypertension by stimulating sodium retention or
      by raising systemic vascular resistance has not been established. In the current
      studies, we used a kidney cross-transplantation strategy to determine whether
      increased sodium reabsorption by AT(1) receptors in the kidney mediates the
      chronic hypertensive response to angiotensin II. We found this to be true. In
      addition, we also identified a second, nontrivial component of blood pressure
      elevation induced by activation of renal AT(1) receptors that is sodium
      independent. As the kidney has the capacity to limit the transmission of elevated
      systemic blood pressure into the renal microcirculation, prior studies struggled
      to clearly discriminate the relative contributions of blood pressure elevation
      vs. activation of AT(1) receptors to hypertensive kidney injury. In our model, we
      found that rapid surges in blood pressure, which may overcome the kidney's
      capacity to prevent perturbations in renal hemodynamics, correlate closely with
      kidney damage in hypertension. Moreover, maximal kidney injury in hypertension
      may require activation of a pool of nonrenal, systemic AT(1) receptors. These
      studies provide insight into precise mechanisms through which AT(1) receptor
      blockade influences the progression of hypertensive kidney disease.

PMID- 21849492
TI  - Modulation of outer medullary NaCl transport and oxygenation by nitric oxide and
      superoxide.
AB  - We expanded our region-based model of water and solute exchanges in the rat outer
      medulla to incorporate the transport of nitric oxide (NO) and superoxide (O(2)(
      )) and to examine the impact of NO-O(2)(-) interactions on medullary thick
      ascending limb (mTAL) NaCl reabsorption and oxygen (O(2)) consumption, under both
      physiological and pathological conditions. Our results suggest that NaCl
      transport and the concentrating capacity of the outer medulla are substantially
      modulated by basal levels of NO and O(2)(-). Moreover, the effect of each solute
      on NaCl reabsorption cannot be considered in isolation, given the feedback loops
      resulting from three-way interactions between O(2), NO, and O(2)(-).
      Notwithstanding vasoactive effects, our model predicts that in the absence of
      O(2)(-)-mediated stimulation of NaCl active transport, the outer medullary
      concentrating capacity (evaluated as the collecting duct fluid osmolality at the
      outer-inner medullary junction) would be ~40% lower. Conversely, without NO
      induced inhibition of NaCl active transport, the outer medullary concentrating
      capacity would increase by ~70%, but only if that anaerobic metabolism can
      provide up to half the maximal energy requirements of the outer medulla. The
      model suggests that in addition to scavenging NO, O(2)(-) modulates NO levels
      indirectly via its stimulation of mTAL metabolism, leading to reduction of O(2)
      as a substrate for NO. When O(2)(-) levels are raised 10-fold, as in hypertensive
      animals, mTAL NaCl reabsorption is significantly enhanced, even as the
      inefficient use of O(2) exacerbates hypoxia in the outer medulla. Conversely, an
      increase in tubular and vascular flows is predicted to substantially reduce mTAL
      NaCl reabsorption. In conclusion, our model suggests that the complex
      interactions between NO, O(2)(-), and O(2) significantly impact the O(2) balance
      and NaCl reabsorption in the outer medulla.

PMID- 21849493
TI  - Effect of Ser-129 phosphorylation on interaction of alpha-synuclein with synaptic
      and cellular membranes.
AB  - In the healthy brain, less than 5% of alpha-synuclein (alpha-syn) is
      phosphorylated at serine 129 (Ser(P)-129). However, within Parkinson disease (PD)
      Lewy bodies, 89% of alpha-syn is Ser(P)-129. The effects of Ser(P)-129
      modification on alpha-syn distribution and solubility are poorly understood. As
      alpha-syn normally exists in both membrane-bound and cytosolic compartments, we
      examined the binding and dissociation of Ser(P)-129 alpha-syn and analyzed the
      effects of manipulating Ser(P)-129 levels on alpha-syn membrane interactions
      using synaptosomal membranes and neural precursor cells from alpha-syn-deficient
      mice or transgenic mice expressing human alpha-syn. We first evaluated the
      recovery of the Ser(P)-129 epitope following either alpha-syn membrane binding or
      dissociation. We demonstrate a rapid turnover of Ser(P)-129 during both binding
      to and dissociation from synaptic membranes. Although the membrane binding of WT
      alpha-syn was insensitive to modulation of Ser(P)-129 levels by multiple
      strategies (the use of phosphomimic S129D and nonphosphorylated S129A alpha-syn
      mutants; by enzymatic dephosphorylation of Ser(P)-129 or proteasome inhibitor
      induced elevation in Ser(P)-129; or by inhibition or stable overexpression of
      PLK2), PD mutant Ser(P)-129 alpha-syn showed a preferential membrane association
      compared with WT Ser(P)-129 alpha-syn. Collectively, these data suggest that
      phosphorylation at Ser-129 is dynamic and that the subcellular distribution of
      alpha-syn bearing PD-linked mutations, A30P or A53T, is influenced by the
      phosphorylation state of Ser-129.

PMID- 21849494
TI  - Unique ganglioside recognition strategies for clostridial neurotoxins.
AB  - Botulinum neurotoxins (BoNTs) and tetanus neurotoxin are the causative agents of
      the paralytic diseases botulism and tetanus, respectively. The potency of the
      clostridial neurotoxins (CNTs) relies primarily on their highly specific binding
      to nerve terminals and cleavage of SNARE proteins. Although individual CNTs
      utilize distinct proteins for entry, they share common ganglioside co-receptors.
      Here, we report the crystal structure of the BoNT/F receptor-binding domain in
      complex with the sugar moiety of ganglioside GD1a. GD1a binds in a shallow groove
      formed by the conserved peptide motif E ... H ... SXWY ... G, with additional
      stabilizing interactions provided by two arginine residues. Comparative analysis
      of BoNT/F with other CNTs revealed several differences in the interactions of
      each toxin with ganglioside. Notably, exchange of BoNT/F His-1241 with the
      corresponding lysine residue of BoNT/E resulted in increased affinity for GD1a
      and conferred the ability to bind ganglioside GM1a. Conversely, BoNT/E was not
      able to bind GM1a, demonstrating a discrete mechanism of ganglioside recognition.
      These findings provide a structural basis for ganglioside binding among the CNTs
      and show that individual toxins utilize unique ganglioside recognition
      strategies.

PMID- 21849495
TI  - Ligand-induced conformational changes within a hexameric Acyl-CoA thioesterase.
AB  - Acyl-coenzyme A (acyl-CoA) thioesterases play a crucial role in the metabolism of
      activated fatty acids, coenzyme A, and other metabolic precursor molecules
      including arachidonic acid and palmitic acid. These enzymes hydrolyze coenzyme A
      from acyl-CoA esters to mediate a range of cellular functions including beta
      oxidation, lipid biosynthesis, and signal transduction. Here, we present the
      crystal structure of a hexameric hot-dog domain-containing acyl-CoA thioesterase
      from Bacillus halodurans in the apo-form and provide structural and comparative
      analyses to the coenzyme A-bound form to identify key conformational changes
      induced upon ligand binding. We observed dramatic ligand-induced changes at both
      the hot-dog dimer and the trimer-of-dimer interfaces; the dimer interfaces in the
      apo-structure differ by over 20% and decrease to about half the size in the
      ligand-bound state. We also assessed the specificity of the enzyme against a
      range of fatty acyl-CoA substrates and have identified a preference for short
      chain fatty acyl-CoAs. Coenzyme A was shown both to negatively regulate enzyme
      activity, representing a direct inhibitory feedback, and consistent with the
      structural data, to destabilize the quaternary structure of the enzyme. Coenzyme
      A-induced conformational changes in the C-terminal helices of enzyme were
      assessed through mutational analysis and shown to play a role in regulating
      enzyme activity. The conformational changes are likely to be conserved from
      bacteria through to humans and provide a greater understanding, particularly at a
      structural level, of thioesterase function and regulation.

PMID- 21849496
TI  - Recent transcription-induced histone H3 lysine 4 (H3K4) methylation inhibits gene
      reactivation.
AB  - Recent transcription of GAL genes transiently leaves an H3K4 methylation mark at
      their promoters, providing an epigenetic memory for the recent transcriptional
      activity. However, the physiological significance of this mark is enigmatic. In
      our study, we show that the transient H3K4 di- and trimethylation at recently
      transcribed GAL1 inhibited the reinduction of GAL1. The H3K4 methylation
      functioned by recruiting the Isw1 ATPase onto GAL1 and thereby limiting the
      action of RNA polymerase II during GAL1 reactivation. Strikingly, the H3K4
      methylation was also observed at the promoters of inositol- and fatty acid
      responsive genes after recent transcription and played a negative role in their
      reinduction. Taken together, our data present a new mechanism by which H3K4
      methylation regulates gene transcription.

PMID- 21849497
TI  - The transcription factor neural retina leucine zipper (NRL) controls
      photoreceptor-specific expression of myocyte enhancer factor Mef2c from an
      alternative promoter.
AB  - Neural retina leucine zipper (NRL) is an essential transcription factor for cell
      fate specification and functional maintenance of rod photoreceptors in the
      mammalian retina. In the Nrl(-/-) mouse retina, photoreceptor precursors fail to
      produce rods and generate functional cone photoreceptors that predominantly
      express S-opsin. Previous global expression analysis using microarrays revealed
      dramatically reduced expression of myocyte enhancer factor Mef2c in the adult
      Nrl(-/-) retina. We undertook this study to examine the biological relevance of
      Mef2c expression in retinal rod photoreceptors. Bioinformatics analysis, rapid
      analysis of cDNA ends (5'-RACE), and reverse transcription coupled with qPCR
      using splice site-specific oligonucleotides suggested that Mef2c is expressed in
      the mature retina from an alternative promoter. Chromatin immunoprecipitation
      (ChIP) studies showed the association of active RNA polymerase II and acetylated
      histone H3 just upstream of Mef2c exon 4, providing additional evidence for the
      utilization of an alternative promoter in the retina. In concordance, we observed
      the binding of NRL to a putative NRL-response element (NRE) at this location by
      ChIP-seq and electrophoretic mobility shift assays. NRL also activated the Mef2c
      alternative promoter in vitro and in vivo. Notably, MEF2C could support Rhodopsin
      promoter activity in rod photoreceptors. We conclude that Mef2c expression from
      an alternative promoter in the retina is regulated by NRL. Our studies also
      implicate MEF2C as a transcriptional regulator of homeostasis in rod
      photoreceptor cells.

PMID- 21849499
TI  - Selenoprotein K is a novel target of m-calpain, and cleavage is regulated by Toll
      like receptor-induced calpastatin in macrophages.
AB  - Calpains are proteolytic enzymes that modulate cellular function through cleavage
      of targets, thereby modifying their actions. An important role is emerging for
      calpains in regulating inflammation and immune responses, although specific
      mechanisms by which this occurs have not been clearly defined. In this study, we
      identify a novel target of calpain, selenoprotein K (SelK), which is an
      endoplasmic reticulum transmembrane protein important for Ca(2+) flux in immune
      cells. Calpain-mediated cleavage of SelK was detected in myeloid cells
      (macrophages, neutrophils, and dendritic cells) but not in lymphoid cells (B and
      T cells). Both m- and MU-calpain were capable of cleaving immunoprecipitated
      SelK, but m-calpain was the predominant isoform expressed in mouse immune cells.
      Consistent with these results, specific inhibitors were used to show that only m
      calpain cleaved SelK in macrophages. The cleavage site in SelK was identified
      between Arg(81) and Gly(82) and the resulting truncated SelK was shown to lack
      selenocysteine, the amino acid that defines selenoproteins. Resting macrophages
      predominantly expressed cleaved SelK and, when activated through different Toll
      like receptors (TLRs), SelK cleavage was inhibited. We found that decreased
      calpain cleavage was due to TLR-induced up-regulation of the endogenous
      inhibitor, calpastatin. TLR-induced calpastatin expression not only inhibited
      SelK cleavage, but cleavage of another calpain target, talin. Moreover, the
      expression of the calpain isoforms and calpastatin in macrophages were different
      from T and B cells. Overall, our findings identify SelK as a novel calpain target
      and reveal dynamic changes in the calpain/calpastatin system during TLR-induced
      activation of macrophages.

PMID- 21849498
TI  - Mammalian testis-determining factor SRY and the enigma of inherited human sex
      reversal: frustrated induced fit in a bent protein-DNA complex.
AB  - Mammalian testis-determining factor SRY contains a high mobility group box, a
      conserved eukaryotic motif of DNA bending. Mutations in SRY cause XY gonadal
      dysgenesis and somatic sex reversal. Although such mutations usually arise de
      novo in spermatogenesis, some are inherited and so specify male development in
      one genetic background (the father) but not another (the daughter). Here, we
      describe the biophysical properties of a representative inherited mutation, V60L,
      within the minor wing of the L-shaped domain (box position 5). Although the
      stability and DNA binding properties of the mutant domain are similar to those of
      wild type, studies of SRY-induced DNA bending by subnanosecond time-resolved
      fluorescence resonance energy transfer (FRET) revealed enhanced conformational
      fluctuations leading to long range variation in bend angle. (1)H NMR studies of
      the variant protein-DNA complex demonstrated only local perturbations near the
      mutation site. Because the minor wing of SRY folds on DNA binding, the inherited
      mutation presumably hinders induced fit. Stopped-flow FRET studies indicated that
      such frustrated packing leads to accelerated dissociation of the bent complex.
      Studies of SRY-directed transcriptional regulation in an embryonic gonadal cell
      line demonstrated partial activation of downstream target Sox9. Our results have
      demonstrated a nonlocal coupling between DNA-directed protein folding and protein
      directed DNA bending. Perturbation of this coupling is associated with a genetic
      switch poised at the threshold of activity.

PMID- 21849500
TI  - An artificial antigen-presenting cell with paracrine delivery of IL-2 impacts the
      magnitude and direction of the T cell response.
AB  - Artificial antigen-presenting cells (aAPCs) are an emerging technology to induce
      therapeutic cellular immunity without the need for autologous antigen-presenting
      cells (APCs). To fully replace natural APCs, an optimized aAPC must present
      antigen (signal 1), provide costimulation (signal 2), and release cytokine
      (signal 3). Here we demonstrate that the spatial and temporal characteristics of
      paracrine release of IL-2 from biodegradable polymer aAPCs (now termed paAPCs)
      can significantly alter the balance in the activation and proliferation of CD8+
      and CD4+ T cells. Paracrine delivery of IL-2 upon T cell contact with paAPCs
      induces significant IL-2 accumulation in the synaptic contact region. This
      accumulation increases CD25 (the inducible IL-2 Ralpha chain) on responding T
      cells and increases proliferation of CD8+ T cells in vitro to levels 10 times
      that observed with equivalent amounts of bulk IL-2. These CD8+ T cell responses
      critically depend upon close contact of T cells and the paAPCs and require
      sustained release of low levels of IL-2. The same conditions promote activation
      induced cell death in CD4+ T cells. These findings provide insight into the
      response of T cell subsets to paracrine IL-2.

PMID- 21849501
TI  - Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9
      (H3K9) acetylation patterns in embryonic stem cells.
AB  - Embryonic stem cell (ESC) chromatin is characterized by a unique set of histone
      modifications, including enrichment for H3 lysine 9 acetylation (H3K9ac). Recent
      studies suggest that histone deacetylase (HDAC) inhibitors promote pluripotency.
      Here, using H3K9ac ChIP followed by high throughput sequencing analyses and gene
      expression in E14 mouse ESCs before and after treatment with a low level of the
      HDAC inhibitor valproic acid, we show that H3K9ac is enriched at gene promoters
      and is highly correlated with gene expression and with various genomic features,
      including different active histone marks and pluripotency-related transcription
      factors. Curiously, it predicts the cellular location of gene products. Treatment
      of ESCs with valproic acid leads to a pervasive genome-wide and time-dependent
      increase in H3K9ac, but this increase is selectively suppressed after 4 h in
      H3K4me3/H3K27me3 bivalent genes. H3K9ac increase is dependent on the promoter's
      chromatin state and is affected by the binding of P300, various transcription
      factors, and active histone marks. This study provides insights into the genomic
      response of ESCs to a low level of HDAC inhibitor, which leads to increased
      pluripotency. The results suggest that a mild (averaging less than 40%) but
      global change in the chromatin state is involved in increased pluripotency and
      that specific mechanisms operate selectively in bivalent genes to maintain
      constant H3K9ac levels. Our data support the notion that H3K9ac has an important
      role in ESC biology.

PMID- 21849502
TI  - Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2
      protein C terminus and inhibits Gcn2 activity.
AB  - The eukaryotic elongation factor 1A (eEF1A) delivers aminoacyl-tRNAs to the
      ribosomal A-site during protein synthesis. To ensure a continuous supply of amino
      acids, cells harbor the kinase Gcn2 and its effector protein Gcn1. The ultimate
      signal for amino acid shortage is uncharged tRNAs. We have proposed a model for
      sensing starvation, in which Gcn1 and Gcn2 are tethered to the ribosome, and Gcn1
      is directly involved in delivering uncharged tRNAs from the A-site to Gcn2 for
      its subsequent activation. Gcn1 and Gcn2 are large proteins, and these proteins
      as well as eEF1A access the A-site, leading us to investigate whether there is a
      functional or physical link between these proteins. Using Saccharomyces
      cerevisiae cells expressing His(6)-eEF1A and affinity purification, we found that
      eEF1A co-eluted with Gcn2. Furthermore, Gcn2 co-immunoprecipitated with eEF1A,
      suggesting that they reside in the same complex. The purified GST-tagged Gcn2 C
      terminal domain (CTD) was sufficient for precipitating eEF1A from whole cell
      extracts generated from gcn2Delta cells, independently of ribosomes. Purified GST
      Gcn2-CTD and purified His(6)-eEF1A interacted with each other, and this was
      largely independent of the Lys residues in Gcn2-CTD known to be required for tRNA
      binding and ribosome association. Interestingly, Gcn2-eEF1A interaction was
      diminished in amino acid-starved cells and by uncharged tRNAs in vitro,
      suggesting that eEF1A functions as a Gcn2 inhibitor. Consistent with this
      possibility, purified eEF1A reduced the ability of Gcn2 to phosphorylate its
      substrate, eIF2alpha, but did not diminish Gcn2 autophosphorylation. These
      findings implicate eEF1A in the intricate regulation of Gcn2 and amino acid
      homeostasis.

PMID- 21849503
TI  - Control of proteobacterial central carbon metabolism by the HexR transcriptional
      regulator: a case study in Shewanella oneidensis.
AB  - Bacteria exploit multiple mechanisms for controlling central carbon metabolism
      (CCM). Thus, a bioinformatic analysis together with some experimental data
      implicated the HexR transcriptional factor as a global CCM regulator in some
      lineages of Gammaproteobacteria operating as a functional replacement of the Cra
      regulator characteristic of Enterobacteriales. In this study, we combined a large
      scale comparative genomic reconstruction of HexR-controlled regulons in 87
      species of Proteobacteria with the detailed experimental analysis of the HexR
      regulatory network in the Shewanella oneidensis model system. Although nearly all
      of the HexR-controlled genes are associated with CCM, remarkable variations were
      revealed in the scale (from 1 to 2 target operons in Enterobacteriales up to 20
      operons in Aeromonadales) and gene content of HexR regulons between 11 compared
      lineages. A predicted 17-bp pseudo-palindrome with a consensus tTGTAATwwwATTACa
      was confirmed as a HexR-binding motif for 15 target operons (comprising 30 genes)
      by in vitro binding assays. The negative effect of the key CCM intermediate, 2
      keto-3-deoxy-6-phosphogluconate, on the DNA-regulator complex formation was
      verified. A dual mode of HexR action on various target promoters, repression of
      genes involved in catabolic pathways and activation of gluconeogenic genes, was
      for the first time predicted by the bioinformatic analysis and experimentally
      verified by changed gene expression pattern in S. oneidensis DeltahexR mutant.
      Phenotypic profiling revealed the inability of this mutant to grow on lactate or
      pyruvate as a single carbon source. A comparative metabolic flux analysis of wild
      type and mutant strains of S. oneidensis using [(13)C]lactate labeling and GC-MS
      analysis confirmed the hypothesized HexR role as a master regulator of
      gluconeogenic flux from pyruvate via the transcriptional activation of
      phosphoenolpyruvate synthase (PpsA).

PMID- 21849504
TI  - Rcl1 protein, a novel nuclease for 18 S ribosomal RNA production.
AB  - In all forms of life, rRNAs for the small and large ribosomal subunit are co
      transcribed as a single transcript. Although this ensures the equimolar
      production of rRNAs, it requires the endonucleolytic separation of pre-rRNAs to
      initiate rRNA production. In yeast, processing of the primary transcript encoding
      18 S, 5.8 S, and 25 S rRNAs has been studied extensively. Nevertheless, most
      nucleases remain to be identified. Here, we show that Rcl1, conserved in all
      eukaryotes, cleaves pre-rRNA at so-called site A(2), a co-transcriptional
      cleavage step that separates rRNAs destined for the small and large subunit.
      Recombinant Rcl1 cleaves pre-rRNA mimics at site A(2) in a reaction that is
      sensitive to nearby RNA mutations that inhibit cleavage in vivo. Furthermore,
      mutations in Rcl1 disrupt rRNA processing at site A(2) in vivo and in vitro.
      Together, these results demonstrate that the role of Rcl1 in eukaryotic pre-rRNA
      processing is identical to that of RNase III in bacteria: to co-transcriptionally
      separate the pre-rRNAs destined for the small and large subunit. Furthermore,
      because Rcl1 has no homology to other known endonucleases, these data also
      establish a novel class of nucleases.

PMID- 21849505
TI  - The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2.
AB  - The inhibitors of apoptosis (IAPs) are critical regulators of apoptosis and other
      fundamental cellular processes. Many IAPs are RING domain-containing ubiquitin E3
      ligases that control the stability of their interacting proteins. However, how
      IAP stability is regulated remains unclear. Here we report that USP19, a
      deubiquitinating enzyme, interacts with cellular IAP 1 (c-IAP1) and c-IAP2.
      Knockdown of USP19 decreases levels of both c-IAPs, whereas overexpression of
      USP19 results in a marked increase in c-IAP levels. USP19 effectively removes
      ubiquitin from c-IAPs in vitro, but it stabilizes c-IAPs in vivo mainly through
      deubiquitinase-independent mechanisms. The deubiquitinase activity is involved in
      the stabilization of USP19 itself, which is facilitated by USP19 self
      association. Functionally, knockdown of USP19 enhances TNFalpha-induced caspase
      activation and apoptosis in a c-IAP1 and 2-dependent manner. These results
      suggest that the self-ubiquitin ligase activity of c-IAPs is inhibited by USP19
      and implicate deubiquitinating enzymes in the regulation of IAP stability.

PMID- 21849506
TI  - Orphan macrodomain protein (human C6orf130) is an O-acyl-ADP-ribose deacylase:
      solution structure and catalytic properties.
AB  - Post-translational modification of proteins/histones by lysine acylation has
      profound effects on the physiological function of modified proteins. Deacylation
      by NAD(+)-dependent sirtuin reactions yields as a product O-acyl-ADP-ribose,
      which has been implicated as a signaling molecule in modulating cellular
      processes. Macrodomain-containing proteins are reported to bind NAD(+)-derived
      metabolites. Here, we describe the structure and function of an orphan
      macrodomain protein, human C6orf130. This unique 17-kDa protein is a stand-alone
      macrodomain protein that occupies a distinct branch in the phylogenic tree. We
      demonstrate that C6orf130 catalyzes the efficient deacylation of O-acetyl-ADP
      ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose to produce ADP-ribose
      (ADPr) and acetate, propionate, and butyrate, respectively. Using NMR
      spectroscopy, we solved the structure of C6orf130 in the presence and absence of
      ADPr. The structures showed a canonical fold with a deep ligand (ADPr)-binding
      cleft. Structural comparisons of apo-C6orf130 and the ADPr-C6orf130 complex
      revealed fluctuations of the beta(5)-alpha(4) loop that covers the bound ADPr,
      suggesting that the beta(5)-alpha(4) loop functions as a gate to sequester
      substrate and offer flexibility to accommodate alternative substrates. The ADPr
      C6orf130 complex identified amino acid residues involved in substrate binding and
      suggested residues that function in catalysis. Site-specific mutagenesis and
      steady-state kinetic analyses revealed two critical catalytic residues, Ser-35
      and Asp-125. We propose a catalytic mechanism for deacylation of O-acyl-ADP
      ribose by C6orf130 and discuss the biological implications in the context of
      reversible protein acylation at lysine residues.

PMID- 21849507
TI  - Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves glucose
      metabolism.
AB  - Obesity is a major risk factor for the development of insulin resistance and type
      2 diabetes. Adipose tissue secretes various bioactive molecules, referred to as
      adipokines, whose dysregulation can mediate changes in glucose homeostasis and
      inflammatory responses. Here, we identify C1qdc2/CTRP12 as an insulin-sensitizing
      adipokine that is abundantly expressed by fat tissues and designate this
      adipokine as adipolin (adipose-derived insulin-sensitizing factor). Adipolin
      expression in adipose tissue and plasma was reduced in rodent models of obesity.
      Adipolin expression was also decreased in cultured 3T3-L1 adipocytes by treatment
      with inducers of endoplasmic reticulum stress and inflammation. Systemic
      administration of adipolin ameliorated glucose intolerance and insulin resistance
      in diet-induced obese mice. Adipolin administration also reduced macrophage
      accumulation and proinflammatory gene expression in the adipose tissue of obese
      mice. Conditioned medium from adipolin-expressing cells diminished the expression
      of proinflammatory cytokines in response to stimulation with LPS or TNFalpha in
      cultured macrophages. These data suggest that adipolin functions as an anti
      inflammatory adipokine that exerts beneficial actions on glucose metabolism.
      Therefore, adipolin represents a new target molecule for the treatment of insulin
      resistance and diabetes.

PMID- 21849508
TI  - Growth hormone induces hepatic production of fibroblast growth factor 21 through
      a mechanism dependent on lipolysis in adipocytes.
AB  - Fibroblast growth factor (FGF) 21 and growth hormone (GH) are metabolic hormones
      that play important roles in regulating glucose and lipid metabolism. Both
      hormones are induced in response to fasting and exert their actions on adipocytes
      to regulate lipolysis. However, the molecular interaction between these two
      hormones remains unclear. Here we demonstrate the existence of a feedback loop
      between GH and FGF21 on the regulation of lipolysis in adipocytes. A single bolus
      injection of GH into C57 mice acutely increases both mRNA and protein expression
      of FGF21 in the liver, thereby leading to a marked elevation of serum FGF21
      concentrations. Such a stimulatory effect of GH on hepatic FGF21 production is
      abrogated by pretreatment of mice with the lipolysis inhibitor niacin. Direct
      incubation of either liver explants or human HepG2 hepatocytes with GH has no
      effect on FGF21 expression. On the other hand, FGF21 production in HepG2 cells is
      significantly induced by incubation with the conditioned medium harvested from GH
      treated adipose tissue explants, which contains high concentrations of free fatty
      acids (FFA). Further analysis shows that FFA released by GH-induced lipolysis
      stimulates hepatic FGF21 expression by activation of the transcription factor
      PPARalpha. In FGF21-null mice, both the magnitude and duration of GH-induced
      lipolysis are significantly higher than those in their wild type littermates.
      Taken together, these findings suggest that GH-induced hepatic FGF21 production
      is mediated by FFA released from adipose tissues, and elevated FGF21 in turn acts
      as a negative feedback signal to terminate GH-stimulated lipolysis in adipocytes.

PMID- 21849509
TI  - Structural basis for agonism and antagonism for a set of chemically related
      progesterone receptor modulators.
AB  - The progesterone receptor is able to bind to a large number and variety of
      ligands that elicit a broad range of transcriptional responses ranging from full
      agonism to full antagonism and numerous mixed profiles inbetween. We describe
      here two new progesterone receptor ligand binding domain x-ray structures bound
      to compounds from a structurally related but functionally divergent series, which
      show different binding modes corresponding to their agonistic or antagonistic
      nature. In addition, we present a third progesterone receptor ligand binding
      domain dimer bound to an agonist in monomer A and an antagonist in monomer B,
      which display binding modes in agreement with the earlier observation that
      agonists and antagonists from this series adopt different binding modes.

PMID- 21849510
TI  - Topology of 1-acyl-sn-glycerol-3-phosphate acyltransferases SLC1 and ALE1 and
      related membrane-bound O-acyltransferases (MBOATs) of Saccharomyces cerevisiae.
AB  - In yeast, phosphatidic acid, the biosynthetic precursor for all
      glycerophospholipids and triacylglycerols, is made de novo by the 1-acyl-sn
      glycerol-3-phosphate acyltransferases Ale1p and Slc1p. Ale1p belongs to the
      membrane-bound O-acyltransferase (MBOAT) family, which contains many enzymes
      acylating lipids but also others that acylate secretory proteins residing in the
      lumen of the ER. A histidine present in a very short loop between two predicted
      transmembrane domains is the only residue that is conserved throughout the MBOAT
      gene family. The yeast MBOAT proteins of known function comprise Ale1p, the
      ergosterol acyltransferases Are1p and Are2p, and Gup1p, the last of which
      acylates lysophosphatidylinositol moieties of GPI anchors on ER lumenal GPI
      proteins. C-terminal topology reporters added to truncated versions of Gup1p
      yield a topology predicting a lumenal location of its uniquely conserved
      histidine 447 residue. The same approach shows that Ale1p and Are2p also have the
      uniquely conserved histidine residing in the ER lumen. Because these data raised
      the possibility that phosphatidic acid could be made in the lumen of the ER, we
      further investigated the topology of the second yeast 1-acyl-sn-glycerol-3
      phosphate acyltransferase, Slc1p. The location of C-terminal topology reporters,
      microsomal assays probing the protease sensitivity of inserted tags, and the
      accessibility of natural or artificially inserted cysteines to membrane
      impermeant alkylating agents all indicate that the most conserved motif
      containing the presumed active site histidine of Slc1p is oriented toward the ER
      lumen, whereas other conserved motifs are cytosolic. The implications of these
      findings are discussed.

PMID- 21849512
TI  - Fibro-osseous pseudotumour of the metacarpal.

PMID- 21849511
TI  - Group V phospholipase A2 in bone marrow-derived myeloid cells and bronchial
      epithelial cells promotes bacterial clearance after Escherichia coli pneumonia.
AB  - Group V-secreted phospholipase A(2) (GV sPLA(2)) hydrolyzes bacterial
      phospholipids and initiates eicosanoid biosynthesis. Here, we elucidate the role
      of GV sPLA(2) in the pathophysiology of Escherichia coli pneumonia. Inflammatory
      cells and bronchial epithelial cells both express GV sPLA(2) after pulmonary E.
      coli infection. GV(-/-) mice accumulate fewer polymorphonuclear leukocytes in
      alveoli, have higher levels of E. coli in bronchoalveolar lavage fluid and lung,
      and develop respiratory acidosis, more severe hypothermia, and higher IL-6, IL
      10, and TNF-alpha levels than GV(+/+) mice after pulmonary E. coli infection.
      Eicosanoid levels in bronchoalveolar lavage are similar in GV(+/+) and GV(-/-)
      mice after lung E. coli infection. In contrast, GV(+/+) mice have higher levels
      of prostaglandin D(2) (PGD(2)), PGF(2alpha), and 15-keto-PGE(2) in lung and
      express higher levels of ICAM-1 and PECAM-1 on pulmonary endothelial cells than
      GV(-/-) mice after lung infection with E. coli. Selective deletion of GV sPLA(2)
      in non-myeloid cells impairs leukocyte accumulation after pulmonary E. coli
      infection, and lack of GV sPLA(2) in either bone marrow-derived myeloid cells or
      non-myeloid cells attenuates E. coli clearance from the alveolar space and the
      lung parenchyma. These observations show that GV sPLA(2) in bone marrow-derived
      myeloid cells as well as non-myeloid cells, which are likely bronchial epithelial
      cells, participate in the regulation of the innate immune response to pulmonary
      infection with E. coli.

PMID- 21849513
TI  - Improvement in pinch function after surgical treatment for thumb in the plane of
      the hand.
AB  - Thumb in the plane of the hand (TPH) is a congenital deformity in which the nail
      plane of the radial-most digit is parallel to that of other digits, but
      structurally the digit retains the characteristics of a thumb. Four hands from
      four patients were retrospectively diagnosed as having TPH, with the underlying
      congenital conditions being symbrachydactyly, cleft hand and constriction band
      syndrome. Thumb web-plasty was carried out in all hands; one required additional
      rotation osteotomy of the metacarpal. Postoperative hand function was markedly
      improved and pinch function was possible in all cases. In most cases of TPH, the
      thumb has the potential to act in opposition, indicating that a thumb web-plasty
      is worth considering as an initial procedure.

PMID- 21849514
TI  - Phytoplasma effector SAP54 induces indeterminate leaf-like flower development in
      Arabidopsis plants.
AB  - Phytoplasmas are insect-transmitted bacterial plant pathogens that cause
      considerable damage to a diverse range of agricultural crops globally. Symptoms
      induced in infected plants suggest that these phytopathogens may modulate
      developmental processes within the plant host. We report herein that Aster
      Yellows phytoplasma strain Witches' Broom (AY-WB) readily infects the model plant
      Arabidopsis (Arabidopsis thaliana) ecotype Columbia, inducing symptoms that are
      characteristic of phytoplasma infection, such as the production of green leaf
      like flowers (virescence and phyllody) and increased formation of stems and
      branches (witches' broom). We found that the majority of genes encoding secreted
      AY-WB proteins (SAPs), which are candidate effector proteins, are expressed in
      Arabidopsis and the AY-WB insect vector Macrosteles quadrilineatus (Hemiptera;
      Cicadellidae). To identify which of these effector proteins induce symptoms of
      phyllody and virescence, we individually expressed the effector genes in
      Arabidopsis. From this screen, we have identified a novel AY-WB effector protein,
      SAP54, that alters floral development, resulting in the production of leaf-like
      flowers that are similar to those produced by plants infected with this
      phytoplasma. This study offers novel insight into the effector profile of an
      insect-transmitted plant pathogen and reports to our knowledge the first example
      of a microbial pathogen effector protein that targets flower development in a
      host.

PMID- 21849516
TI  - Pharmacokinetic differences corroborate observed low tacrolimus dosage in Native
      American renal transplant patients.
AB  - We have observed in clinical practice that Native Americans require lower dosages
      of tacrolimus to attain similar target blood trough levels compared to whites
      after renal transplant. Because there are no pharmacokinetic studies of
      tacrolimus in this ethnic group, we investigated whether this clinical
      observation could be corroborated by pharmacokinetic differences between Native
      Americans and other ethnic and racial groups. We recruited 24 adult Native
      American kidney transplant recipients on stable oral doses of tacrolimus for at
      least 1 month posttransplant. We conducted a 12-h steady-state pharmacokinetic
      profile for all of the patients and estimated pharmacokinetic parameters using
      NONMEM. The concentration-time data were fit to a linear two compartment model
      with first-order absorption and lag time using an empirical Bayesian approach.
      The mean estimate of oral clearance (CL/F) was 11.1 l/h. Compared with previously
      reported data in other ethnic and racial groups, the Native American cohort has
      approximately one third the clearance of other groups. Our pharmacokinetic study
      reveals the clinically observed low dose of tacrolimus in Native American renal
      transplant patients is associated with a decreased oral tacrolimus clearance.
      There is scant information available on the genetic or environmental
      characteristics unique to this ethnic group that affect pharmacokinetics compared
      to other, better-studied groups, and elucidation of these factors will provide
      information to further facilitate individualized drug treatment for tacrolimus
      and a wide range of other drugs with similar clearance processes.

PMID- 21849515
TI  - A large-scale genetic screen in Arabidopsis to identify genes involved in pollen
      exine production.
AB  - Exine, the outer plant pollen wall, has elaborate species-specific patterns,
      provides a protective barrier for male gametophytes, and serves as a mediator of
      strong and species-specific pollen-stigma adhesion. Exine is made of
      sporopollenin, a material remarkable for its strength, elasticity, and chemical
      durability. The chemical nature of sporopollenin, as well as the developmental
      mechanisms that govern its assembly into diverse patterns in different species,
      are poorly understood. Here, we describe a simple yet effective genetic screen in
      Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our
      understanding of sporopollenin synthesis and exine assembly. This screen led to
      the recovery of mutants with a variety of defects in exine structure, including
      multiple mutants with novel phenotypes. Fifty-six mutants were selected for
      further characterization and are reported here. In 14 cases, we have mapped
      defects to specific genes, including four with previously demonstrated or
      suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC
      PROTEIN6, TETRAKETIDE alpha-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1),
      and a number of genes that have not been implicated in exine production prior to
      this screen (among them, fatty acid omega-hydroxylase CYP704B1, putative glycosyl
      transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3,
      polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar
      transporter At5g65000). Our study illustrates that morphological screens of
      pollen can be extremely fruitful in identifying previously unknown exine genes
      and lays the foundation for biochemical, developmental, and evolutionary studies
      of exine production.

PMID- 21849517
TI  - Digoxin is not a substrate for organic anion-transporting polypeptide
      transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a substrate for a
      sodium-dependent transporter expressed in HEK293 cells.
AB  - Digoxin, an orally administered cardiac glycoside cardiovascular drug, has a
      narrow therapeutic window. Circulating digoxin levels (maximal concentration of
      ~1.5 ng/ml) require careful monitoring, and the potential for drug-drug
      interactions (DDI) is a concern. Increases in digoxin plasma exposure caused by
      inhibition of P-glycoprotein (P-gp) have been reported. Digoxin has also been
      described as a substrate of various organic anion-transporting polypeptide (OATP)
      transporters, posing a risk that inhibition of OATPs may result in a clinically
      relevant DDI similar to what has been observed for P-gp. Although studies in rats
      have shown that Oatps contribute to the disposition of digoxin, the role of OATPs
      in the disposition of digoxin in humans has not been clearly defined. Using two
      methods, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, and Solvo observed that
      digoxin is not a substrate of OATP1A2, OATP1B1, OATP1B3, and OATP2B1. However,
      digoxin inhibited the uptake of probe substrates of OATP1B1 (IC(50) of 47 MUM),
      OATP1B3 (IC(50) > 8.1 MUM), and OATP2B1 (IC(50) > 300 MUM), but not OATP1A2 in
      transfected cell lines. It is interesting to note that digoxin is a substrate of
      a sodium-dependent transporter endogenously expressed in HEK293 cells because
      uptake of digoxin was significantly greater in cells incubated with sodium
      fortified media compared with incubations conducted in media in which sodium was
      absent. Thus, although digoxin is not a substrate for the human OATP transporters
      evaluated in this study, in addition to P-gp-mediated efflux, its uptake and
      pharmacokinetic disposition may be partially facilitated by a sodium-dependent
      transporter.

PMID- 21849518
TI  - Evolutionary relationship of the L- and M-class genome segments of bat-borne
      fusogenic orthoreoviruses in Malaysia and Australia.
AB  - We previously described three new Malaysian orthoreoviruses designated Pulau
      virus, Melaka virus and Kampar virus. Melaka and Kampar viruses were shown to
      cause respiratory disease in humans. These viruses, together with Nelson Bay
      virus, isolated from Australian bats, are tentatively classified as different
      strains within the species Pteropine orthoreovirus (PRV), formerly known as
      Nelson Bay orthoreovirus, based on the small (S) genome segments. Here we report
      the sequences of the large (L) and medium (M) segments, thus completing the whole
      genome characterization of the four PRVs. All L and M segments were highly
      conserved in size and sequence. Conserved functional motifs previously identified
      in other orthoreovirus gene products were also found in the deduced proteins
      encoded by the cognate segments of these viruses. Detailed sequence analysis
      identified two genetic lineages divided into the Australian and Malaysian PRVs,
      and potential genetic reassortment among the M and S segments of the three
      Malaysian viruses.

PMID- 21849519
TI  - Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2
      virus highly transmissible among pigs.
AB  - Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine
      populations have been reported in Asia, Europe and North America since 1970. In
      South America, serological surveys in pigs indicate that IAVs of the H3 and H1
      subtypes are currently in circulation; however, neither virus isolation nor
      characterization has been reported. In November 2008, an outbreak of respiratory
      disease in pigs consistent with swine influenza virus (SIV) infection was
      detected in Argentina. The current study describes the clinical epidemiology,
      pathology, and molecular and biological characteristics of the virus.
      Phylogenetic analysis revealed that the virus isolate shared nucleotide
      identities of 96-98 % with H3N2 IAVs that circulated in humans from 2000 to 2003.
      Antigenically, sera from experimentally inoculated animals cross-reacted mainly
      with non-contemporary human-origin H3N2 influenza viruses. In an experimental
      infection in a commercial swine breed, the virus was of low virulence but was
      transmitted efficiently to contact pigs and caused severe disease when an
      infected animal acquired a secondary bacterial infection. This is the first
      report of a wholly human H3N2 IAV associated with clinical disease in pigs in
      South America. These studies highlight the importance of two-way transmission of
      IAVs and SIVs between pigs and humans, and call for enhanced influenza
      surveillance in the pig population worldwide.

PMID- 21849520
TI  - Decreased STAMP2 expression in association with visceral adipose tissue
      dysfunction.
AB  - CONTEXT: Six-transmembrane protein of prostate 2 (STAMP2) is a counter-regulator
      of inflammation and insulin resistance according to findings in mice. However,
      there have been contradictory reports in humans. OBJECTIVE: We aimed to explore
      STAMP2 in association with inflammatory and metabolic status of human obesity.
      DESIGN, PATIENTS, AND METHODS: STAMP2 gene expression was analyzed in adipose
      tissue samples (171 visceral and 67 sc depots) and during human preadipocyte
      differentiation. Human adipocytes were treated with macrophage-conditioned
      medium, TNF-alpha, and rosiglitazone. RESULTS: In visceral adipose tissue, STAMP2
      gene expression was significantly decreased in obese subjects, mainly in obese
      subjects with type 2 diabetes. STAMP2 gene expression and protein were
      significantly and inversely associated with obesity phenotype measures (body mass
      index, waist, hip, and fat mass) and obesity-associated metabolic disturbances
      (systolic blood pressure and fasting glucose). In addition, STAMP2 gene
      expression was positively associated with lipogenic (FASN, ACC1, SREBP1, THRSP14,
      TRalpha, and TRalpha1), CAV1, IRS1, GLUT4, and CD206 gene expression. In sc
      adipose tissue, STAMP2 gene expression was not associated with metabolic
      parameters. In both fat depots, STAMP2 gene expression in stromovascular cells
      was significantly higher than in mature adipocytes. STAMP2 gene expression was
      significantly increased during the differentiation process in parallel to
      adipogenic genes, being increased in preadipocytes derived from lean subjects.
      Macrophage-conditioned medium (25%) and TNF-alpha (100 ng/ml) administration
      increased whereas rosiglitazone (2 MUM) decreased significantly STAMP2 gene
      expression in human differentiated adipocytes. CONCLUSIONS: Decreased STAMP2
      expression (mRNA and protein) might reflect visceral adipose dysfunction in
      subjects with obesity and type 2 diabetes.

PMID- 21849521
TI  - Androgen sulfation in healthy UDP-glucuronosyl transferase 2B17 enzyme-deficient
      men.
AB  - CONTEXT: The conspicuous interindividual differences in metabolism and urinary
      excretion of testosterone and its metabolites make it challenging to reveal
      testosterone doping. The variation in testosterone glucuronide excretion is
      strongly associated with a deletion polymorphism in the uridine diphosphate
      glucuronosyltranferase (UGT) 2B17 gene. OBJECTIVE: The objective of the study was
      to identify additional biomarkers to detect testosterone abuse and to elucidate
      alternative pathways for testosterone elimination in individuals devoid of the
      UGT2B17 enzyme. For this purpose a new ultraperformance liquid chromatographic
      tandem mass spectrometric method for simultaneous determination of 10 different
      sulfo- and glucuronide-conjugated steroids was developed. PARTICIPANTS: Fifty
      four healthy male volunteers with two, one, or no allele (ins/ins, ins/del, or
      del/del) of the UGT2B17 gene participated in the study. INTERVENTION:
      Intervention included a single im dose of 500 mg testosterone enanthate. MAIN
      OUTCOME MEASURES: Urinary sulfo- and glucuronide-conjugated steroids were
      measured. RESULTS: Testosterone sulfate levels decreased in all individuals after
      the dose. The individual differences in the excretion of all sulfated metabolites
      were large. Thus, these metabolites will not serve as appropriate biomarkers for
      testosterone abuse. However, androsterone glucuronide excretion increased in all
      of our study subjects after the testosterone dose. Etiocholanolone sulfate was
      excreted at significantly higher levels in UGT2B17 del/del individuals.
      CONCLUSION: We propose that the androsterone glucuronide to epitestosterone
      glucuronide ratio may serve as a complementary biomarker to reveal testosterone
      abuse.

PMID- 21849522
TI  - The relationships between sex hormones and sexual function in middle-aged and
      older European men.
AB  - CONTEXT: Limited data are available exploring the associations between sex
      hormones, multiple domains of sexual functioning, and sexual function-related
      distress in nonpatient samples in Europe. OBJECTIVES: The aim of the study was to
      investigate the relationships between serum testosterone (T), estradiol (E2), and
      dihydrotestosterone (DHT) and sexual function in a multicenter population-based
      study of aging in men. DESIGN: Using stratified random sampling, 2838 men aged 40
      79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and
      provided a blood sample for hormone measurements. T, E2, and DHT were measured
      using gas chromatography-mass spectrometry. SETTING: We conducted a community
      based population survey in eight European centers. MAIN OUTCOME MEASURES: Self
      reported sexual function (overall sexual function, sexual function-related
      distress, erectile dysfunction, masturbation) was measured. RESULTS: Total and
      free T, but not E2 or DHT, was associated with overall sexual function in middle
      aged and older men. E2 was the only hormone associated with sexual function
      related distress such that higher levels were related to greater distress. Free T
      levels were associated with masturbation frequency and erectile dysfunction in
      the fully adjusted models, such that higher T was associated with less
      dysfunction and greater frequency. Moreover, there was a T threshold for the
      relationship between total T, sexual function, and erectile dysfunction. At T
      concentrations of 8 nmol/liter or less, T was associated with worse sexual
      functioning, whereas at T levels over 8 nmol/liter, the relationship came to a
      plateau. CONCLUSIONS: These findings suggest that different hormonal mechanisms
      may regulate sexual functioning (T) vs. the psychological aspects (E2) of male
      sexual behavior. Moreover, there was a T threshold for overall sexual function
      such that at levels greater than 8 nmol/liter the relationship between T and
      sexual function did not become stronger.

PMID- 21849523
TI  - Cardiac natriuretic peptides, obesity, and insulin resistance: evidence from two
      community-based studies.
AB  - BACKGROUND: The natriuretic peptides play an important role in salt homeostasis
      and blood pressure regulation. It has been suggested that obesity promotes a
      relative natriuretic peptide deficiency, but this has been a variable finding in
      prior studies and the cause is unknown. AIM: The aim of this study was to examine
      the association between obesity and natriuretic peptide levels and evaluate the
      role of hyperinsulinemia and testosterone as mediators of this interaction.
      METHODS: We studied 7770 individuals from the Framingham Heart Study (n = 3833,
      54% women) and the Malmo Diet and Cancer study (n = 3918, 60% women). We examined
      the relation of plasma N-terminal pro-B-type natriuretic peptide levels (N-BNP)
      with obesity, insulin resistance, and various metabolic subtypes. RESULTS:
      Obesity was associated with 6-20% lower levels of N-BNP (P < 0.001 in Framingham,
      P = 0.001 in Malmo), whereas insulin resistance was associated with 10-30% lower
      levels of N-BNP (P < 0.001 in both cohorts). Individuals with obesity who were
      insulin sensitive had only modest reductions in N-BNP compared with nonobese,
      insulin-sensitive individuals. On the other hand, individuals who were nonobese
      but insulin resistant had 26% lower N-BNP in Framingham (P < 0.001) and 10% lower
      N-BNP in Malmo (P < 0.001), compared with nonobese and insulin-sensitive
      individuals. Adjustment for serum-free testosterone did not alter these
      associations. CONCLUSIONS: In both nonobese and obese individuals, insulin
      resistance is associated with lower natriuretic peptide levels. The relative
      natriuretic peptide deficiency seen in obesity could be partly attributable to
      insulin resistance, and could be one mechanism by which insulin resistance
      promotes hypertension.

PMID- 21849524
TI  - Estrogen levels are higher across the menstrual cycle in African-American women
      compared with Caucasian women.
AB  - CONTEXT: Previous studies have suggested that estrogen levels may be higher in
      African-American women (AAW) compared with Caucasian women (CW), but none have
      systematically examined estrogen secretion across the menstrual cycle or in
      relation to other reproductive hormones. OBJECTIVE: The objective of the study
      was to compare estradiol (E2), progesterone (P), gonadotropins, androstenedione
      (a'dione), inhibins, and SHBG levels between AAW and CW across the menstrual
      cycle. DESIGN, SETTING, AND SUBJECTS: Daily blood samples were collected from
      regularly cycling AAW (n = 27) and CW (n = 27) for a full menstrual cycle, and
      serial ultrasounds were performed. MAIN OUTCOME MEASURES: Comparison of E2, P,
      LH, FSH, SHBG, inhibin A, inhibin B, and a'dione levels. RESULTS: AAW and CW were
      of similar age (27.2 +/- 0.6 yr, mean +/- sem) and body mass index (22.7 +/- 0.4
      kg/m(2)). All subjects grew a single dominant follicle and had comparable cycle
      (25-35 d) and follicular phase (11-24 d) lengths. E2 levels were significantly
      higher in AAW compared with CW (P = 0.02) with the most pronounced differences in
      the late follicular phase (225.2 +/- 14.4 vs. 191.5 +/- 10.2 pg/ml; P = 0.02),
      midluteal phase (211.9 +/- 22.2 vs.150.8 +/- 9.9, P < 0.001), and late luteal
      phase (144.4 +/- 13.2 vs. 103.5 +/- 8.5, P = 0.01). Although LH, FSH, inhibins A
      and B, P, a'dione, and SHBG were not different between the two groups, the
      a'dione to E2 ratio was lower in AAW (P < 0.001). CONCLUSIONS: Estradiol is
      higher in AAW compared with CW across the menstrual cycle. Higher estradiol in
      the face of similar androstenedione and FSH levels suggests enhanced aromatase
      activity in AAW. Such differences may contribute to racial disparities in bone
      mineral density, breast cancer, and uterine leiomyomas.

PMID- 21849525
TI  - Tumor expression of human growth hormone and human prolactin predict a worse
      survival outcome in patients with mammary or endometrial carcinoma.
AB  - CONTEXT: Evidence suggests that human GH (hGH) and human prolactin (hPRL) possess
      an autocrine or paracrine oncogenic role in mammary and endometrial carcinoma.
      However, especially for hGH, the prognostic relevance of tumor expression of
      these hormones is not well defined. OBJECTIVE: We investigated the potential
      association of tumor mRNA and protein expression of hGH and hPRL with the
      clinicopathological features of mammary and endometrial carcinoma. The prognostic
      relevance of the individual or combined expression of hGH and hPRL in mammary and
      endometrial carcinoma was also determined. DESIGN: The expression of hGH and hPRL
      was analyzed in histopathological samples of mammary and endometrial carcinoma,
      and the respective normal tissues, by in situ hybridization and
      immunohistochemistry. Kaplan-Meier and Cox regression analysis was performed to
      examine the association of tumor hGH and hPRL expression with relapse-free
      survival and overall survival of patients. RESULTS: hGH expression was
      significantly associated with lymph node metastasis, tumor stage, human epidermal
      growth factor receptor-2 status, and proliferative index in mammary carcinoma and
      with International Federation of Gynecology and Obstetrics grade, myometrial
      invasion, and ovarian metastases in endometrial carcinoma. hPRL expression was
      associated with lymph node metastasis, tumor grade, and tumor stage in mammary
      carcinoma and with International Federation of Gynecology and Obstetrics stage
      and myometrial invasion in endometrial carcinoma. Both hGH and hPRL expression,
      individually and combined, are associated with worse relapse-free survival and
      overall survival in patients with mammary or endometrial carcinoma. CONCLUSION:
      Tumor expression of both hGH or hPRL in mammary or endometrial carcinoma is
      associated with a large and significant difference in survival outcome for
      patients with these tumors.

PMID- 21849526
TI  - Sensitivity and specificity of glycated hemoglobin as a diagnostic test for
      diabetes and prediabetes in Arabs.
AB  - CONTEXT: Glycated hemoglobin (A1C) has been recommended by the American Diabetes
      Association for the diagnosis of diabetes and prediabetes. The diagnostic utility
      of A1C has not been evaluated in Arabs, a population at increased risk for
      developing diabetes. OBJECTIVE: Our objective was to examine the sensitivity and
      specificity of A1C for the diagnosis of diabetes and prediabetes in Arabs. DESIGN
      & SETTING: In this cross-sectional study, glucose tolerance was classified by the
      American Diabetes Association diagnostic criteria specified for A1C, fasting
      plasma glucose, and 75-g oral glucose tolerance test. PARTICIPANTS: A population
      based representative sample of 482 randomly selected adult Arabs without known
      diabetes was studied. MAIN OUTCOME MEASURES: Sensitivity, specificity, and area
      under the receiver operating characteristic curve of A1C diagnostic cutpoints for
      diabetes and prediabetes were calculated. kappa Coefficients were used to test
      for agreement between A1C categorization and glucose-based diagnoses. RESULTS:
      A1C testing correctly identified 5% of individuals diagnosed with diabetes by
      oral glucose tolerance test, 13% by fasting plasma glucose, and 41% by both
      criteria. A1C alone identified 14% of individuals diagnosed with impaired glucose
      tolerance, 9% with impaired fasting glucose, and 33% with both abnormalities.
      Sensitivity, specificity, and area under the receiver operating characteristic
      curve were 19% (16-23%), 100% (99-100%), and 77% (69-85%) for diabetes A1C
      cutpoint and 14% (11-17%), 91% (89-94%), and 57% (52-62%) for prediabetes A1C
      range. A1C cutpoint of 6.2% for diabetes and 5.1% for prediabetes yielded the
      highest accuracy but still missed 73% of those with diabetes and 31% with
      prediabetes. Agreement between A1C and diabetes (kappa = 0.2835) or prediabetes
      (kappa = 0.0530) was low. CONCLUSIONS: A1C-based criteria yield a high proportion
      of false-negative tests for diabetes and prediabetes in Arabs. SUMMARY:
      Racial/ethnic differences in A1C performance for diagnosis and prediction of
      diabetes exist. This paper examines its utility against glucose measurements in
      an at-risk Arab population.

PMID- 21849527
TI  - Wnt/beta-catenin pathway deregulation in childhood adrenocortical tumors.
AB  - CONTEXT: CTNNB1/beta-catenin mutations and activation of Wnt/beta-catenin pathway
      are frequent in adult adrenocortical tumors (ACT), but data on childhood ACT are
      lacking. OBJECTIVE: The aim of the study was to investigate the presence of
      Wnt/beta-catenin pathway abnormalities in childhood ACT. PATIENTS AND METHODS:
      Clinicopathological findings and outcome of 62 childhood ACT patients were
      analyzed regarding CTNNB1 mutations and the expression of Wnt-related genes
      (CTNNB1; WNT4, a Wnt ligand; SFRP1, DKK3, and AXIN1, Wnt inhibitors; TCF7, a
      transcription factor; and MYC and WISP2, target genes) by quantitative PCR and
      immunohistochemistry. RESULTS: CTNNB1-activating mutations were found in only
      four of 62 ACT (6%), all of them harboring TP53 mutation. There was association
      between the presence of CTNNB1 mutations and death (P = 0.02). Diffuse beta
      catenin accumulation was found in 71% of ACT, even in ACT without CTNNB1
      mutations. Compared to normal adrenals, ACT presented increased expression of
      CTNNB1 (P = 0.008) and underexpression of Wnt inhibitor genes: DKK3 (P < 0.0001),
      SFRP1 (P = 0.05), and AXIN1 (P = 0.04). With regard to Wnt/beta-catenin target
      genes, ACT presented increased expression of WISP2 but lower expression of MYC.
      Higher overall survival was associated with underexpression of SFRP1 (P = 0.01),
      WNT4 (P = 0.004), and TCF7 (P < 0.01). CONCLUSIONS: CTNNB1 mutations are not
      common in childhood ACT but appear to associate with poor prognosis.
      Nevertheless, most ACT exhibit increased expression of beta-catenin and WISP2 and
      reduced expression of Wnt inhibitor genes (DKK3, SFRP1, and AXIN1). Thus, in
      addition to CTNNB1 mutations, other genetic events affecting the Wnt/beta-catenin
      pathway may be involved in childhood adrenocortical tumorigenesis.

PMID- 21849528
TI  - Treatment of pediatric Graves' disease is associated with excessive weight gain.
AB  - CONTEXT: Little information is available about changes in body weight and body
      mass index in children before, during, and after treatment for Graves' disease
      (GD). OBJECTIVE: Our objective was to examine changes in body weight after
      treatment for GD in children as related to clinical features. DESIGN: The medical
      records of 43 pediatric patients with GD [35 girls and eight boys, aged 4.0-18.5
      (mean 10.9) yr] were examined. Patients were included if clinical data were
      available for 1 yr before and after the diagnosis of GD. MAIN OUTCOME MEASURES:
      Weight, height, body mass index (BMI) z-scores, and thyroid hormone levels were
      assessed. RESULTS: Overall, patients presented with an average BMI z-score of 
      0.02 +/- 1.05 that was not different from the normal population (P = 0.921) or
      their premorbid values (P = 0.07). However, in the subset of patients who were
      initially overweight or obese in the premorbid state, the BMI decreased
      significantly during the development of hyperthyroidism (P < 0.05). After
      initiation of treatment, patients gained significant amounts of weight over the
      first 6 months leading to elevated BMI z-scores (P < 0.0001), and elevations in
      BMI persisted in about 25% of the patients. CONCLUSION: Excessive weight gain
      within 6 months of treatment is seen in children treated for GD, and the gain in
      weight can persist.

PMID- 21849530
TI  - Efficacy of dosimetric versus empiric prescribed activity of 131I for therapy of
      differentiated thyroid cancer.
AB  - BACKGROUND: The optimal management of high-risk patients with differentiated
      thyroid cancer (DTC) consists of thyroidectomy followed by radioiodine ((131)I)
      therapy. The prescribed activity of (131)I can be determined using two
      approaches: 1) empiric prescribed activity of (131)I (E-Rx); and 2) dosimetry
      based prescribed activity of (131)I (D-Rx). AIM: The aim of the study was to
      compare the relative treatment efficacy and side effects of D-Rx vs. E-Rx.
      METHODS: A retrospective analysis was performed of patients with distant
      metastases and/or locoregionally advanced radioiodine-avid DTC who were treated
      with either D-Rx or E-Rx. Response to treatment was based on RECIST (Response
      Evaluation Criteria in Solid Tumors) 1.1 criteria. RESULTS: The study group
      consisted of 87 patients followed for 51 +/- 35 months, of whom 43 were treated
      with D-Rx and 44 with E-Rx. Multivariate analysis, controlling for age, gender,
      and status of metastases revealed that the D-Rx group tended to be 70% less
      likely to progress (odds ratio, 0.29; 95% confidence interval, 0.087-1.02; P =
      0.052) and more likely to obtain complete response (CR) compared to the E-Rx
      group (odds ratio, 8.2; 95% confidence interval, 1.2-53.5; P = 0.029). There was
      an association in the D-Rx group between the observed CR and percentage of
      maximum tolerable activity given as a first treatment of (131)I (P = 0.030). The
      advantage of D-Rx was specifically apparent in the locoregionally advanced group
      because CR was significantly higher in D-Rx vs. E-Rx in this group of patients
      (35.7 vs. 3.3%; P = 0.009). The rates of partial response, stable disease, and
      progression-free survival, as well as the frequency of side effects, were not
      significantly different between the two groups. CONCLUSION: Higher efficacy of D
      Rx with a similar safety profile compared to E-Rx supports the rationale for
      employing individually prescribed activity in high-risk patients with DTC.

PMID- 21849529
TI  - Consumption of fructose and high fructose corn syrup increase postprandial
      triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women.
AB  - CONTEXT: The American Heart Association Nutrition Committee recommends women and
      men consume no more than 100 and 150 kcal of added sugar per day, respectively,
      whereas the Dietary Guidelines for Americans, 2010, suggests a maximal added
      sugar intake of 25% or less of total energy. OBJECTIVE: To address this
      discrepancy, we compared the effects of consuming glucose, fructose, or high
      fructose corn syrup (HFCS) at 25% of energy requirements (E) on risk factors for
      cardiovascular disease. PARTICIPANTS, DESIGN AND SETTING, AND INTERVENTION: Forty
      eight adults (aged 18-40 yr; body mass index 18-35 kg/m(2)) resided at the
      Clinical Research Center for 3.5 d of baseline testing while consuming energy
      balanced diets containing 55% E complex carbohydrate. For 12 outpatient days,
      they consumed usual ad libitum diets along with three servings per day of
      glucose, fructose, or HFCS-sweetened beverages (n = 16/group), which provided 25%
      E requirements. Subjects then consumed energy-balanced diets containing 25% E
      sugar-sweetened beverages/30% E complex carbohydrate during 3.5 d of inpatient
      intervention testing. MAIN OUTCOME MEASURES: Twenty-four-hour triglyceride area
      under the curve, fasting plasma low-density lipoprotein (LDL), and apolipoprotein
      B (apoB) concentrations were measured. RESULTS: Twenty-four-hour triglyceride
      area under the curve was increased compared with baseline during consumption of
      fructose (+4.7 +/- 1.2 mmol/liter * 24 h, P = 0.0032) and HFCS (+1.8 +/- 1.4
      mmol/liter * 24 h, P = 0.035) but not glucose (-1.9 +/- 0.9 mmol/liter * 24 h, P
      = 0.14). Fasting LDL and apoB concentrations were increased during consumption of
      fructose (LDL: +0.29 +/- 0.082 mmol/liter, P = 0.0023; apoB: +0.093 +/- 0.022
      g/liter, P = 0.0005) and HFCS (LDL: +0.42 +/- 0.11 mmol/liter, P < 0.0001; apoB:
      +0.12 +/- 0.031 g/liter, P < 0.0001) but not glucose (LDL: +0.012 +/- 0.071
      mmol/liter, P = 0.86; apoB: +0.0097 +/- 0.019 g/liter, P = 0.90). CONCLUSIONS:
      Consumption of HFCS-sweetened beverages for 2 wk at 25% E increased risk factors
      for cardiovascular disease comparably with fructose and more than glucose in
      young adults.

PMID- 21849531
TI  - Does growth hormone replacement therapy reduce mortality in adults with growth
      hormone deficiency? Data from the Dutch National Registry of Growth Hormone
      Treatment in adults.
AB  - CONTEXT: Adults with GH deficiency (GHD) have a decreased life expectancy. The
      effect of GH treatment on mortality remains to be established. OBJECTIVE: This
      nationwide cohort study investigates the effect of GH treatment on all-cause and
      cause-specific mortality and analyzes patient characteristics influencing
      mortality in GHD adults. DESIGN, SETTING, AND PATIENTS: Patients in the Dutch
      National Registry of Growth Hormone Treatment in Adults were retrospectively
      monitored (1985-2009) and subdivided into treatment (n = 2229), primary
      (untreated, n = 109), and secondary control (partly treated, n = 356) groups.
      MAIN OUTCOME MEASURES: Standardized mortality ratios (SMR) were calculated for
      all-cause, malignancy, and cardiovascular disease (CVD) mortality. Expected
      mortality was obtained from cause, sex, calendar year, and age-specific death
      rates from national death and population counts. RESULTS: In the treatment group,
      95 patients died compared to 74.6 expected [SMR 1.27 (95% confidence interval,
      1.04-1.56)]. Mortality was higher in women than in men. After exclusion of high
      risk patients, the SMR for CVD mortality remained increased in women. Mortality
      due to malignancies was not elevated. In the control groups mortality was not
      different from the background population. Univariate analyses demonstrated sex,
      GHD onset, age, and underlying diagnosis as influencing factors. CONCLUSIONS: GHD
      men receiving GH treatment have a mortality rate not different from the
      background population. In women, after exclusion of high-risk patients, mortality
      was not different from the background population except for CVD. Mortality due to
      malignancies was not elevated in adults receiving GH treatment. Next to gender,
      the heterogeneous etiology is of influence on mortality in GHD adults with GH
      treatment.

PMID- 21849532
TI  - Prevention of fractures after solid organ transplantation: a meta-analysis.
AB  - CONTEXT: Bone loss and fracture are serious sequelae of organ transplantation,
      particularly in the first posttransplant year. Most interventional studies have
      been inadequately powered to detect effects on fracture. OBJECTIVE: The objective
      of the study was to determine whether treatment with bisphosphonates (BP) or
      active vitamin D analogs (vitD) during the first year after transplantation
      reduces fracture risk and estimate the effect of these interventions on bone
      loss. DATA SOURCES: Sources included PUBMED, MEDLINE, Cochrane Library, and
      abstracts from scientific meetings (presented 2003-2010). STUDY SELECTION:
      Randomized controlled clinical trials of BP or vitD in solid organ transplant
      recipients were included if treatment was initiated at the time of
      transplantation and fracture data were collected. DATA EXTRACTION: Two
      investigators independently extracted data and rated study quality. Fixed effect
      and random-effects models were used to obtain pooled estimates. DATA SYNTHESIS:
      Eleven studies of 780 transplant recipients (134 fractures) were included.
      Treatment with BP or vitD reduced the number of subjects with fracture [odds
      ratio (OR) 0.50 (0.29, 0.83)] and number of vertebral fractures, [OR 0.24 (0.07,
      0.78)]. An increase in bone mineral density at the lumbar spine [2.98% (1.31,
      4.64)] and femoral neck [3.05% (2.16, 3.93)] was found with treatment. When BP
      trials (nine studies, 625 subjects) were examined separately, there was a
      reduction in number of subjects with fractures [OR 0.53 (0.30, 0.91)] but no
      significant reduction in vertebral fractures [OR 0.34 (0.09, 1.24)]. CONCLUSIONS:
      Treatment with BP or vitD during the first year after solid organ transplant was
      associated with a reduction in the number of subjects with fractures and fewer
      vertebral fractures.

PMID- 21849533
TI  - Catecholaminergic axonal varicosities appear to innervate growth hormone
      releasing hormone-immunoreactive neurons in the human hypothalamus: the possible
      morphological substrate of the stress-suppressed growth.
AB  - CONTEXT: Stress is considered to be a major factor in the regulation of growth.
      Psychosocial dwarfism, characterized with short stature, delayed puberty, and
      depression, is typically preceded by psychological harassment or stressful
      environment. It has been observed that stress suppresses GH secretion, possibly
      via the attenuation of GHRH secretion. However, the exact mechanism of the impact
      of stress on growth has not been elucidated yet. OBJECTIVE: Our previous studies
      revealed intimate associations between neuropeptide Y (NPY)-immunoreactive (IR)
      axonal varicosities and GHRH-IR perikarya in the human hypothalamus. Because NPY
      is considered to be a stress molecule, NPY-GHRH juxtapositions may represent an
      important factor of stress-suppressed GHRH release. In addition to NPY,
      catecholamines are among the major markers of stress. Thus, in the present study,
      we examined the putative juxtapositions between the catecholaminergic tyrosine
      hydroxylase (TH)-/dopamine-beta-hydroxylase-/phenylethanolamine N
      methyltransferase-IR and GHRH-IR neural elements in the human hypothalamus. To
      reveal these juxtapositions, double-label immunohistochemistry was used. RESULTS:
      Our findings revealed that the majority of the GHRH-IR perikarya formed intimate
      associations with TH-IR fiber varicosities. The majority of these juxtapositions
      were found in the infundibular nucleus/median eminence. CONCLUSIONS: The lack of
      phenylethanolamine N-methyltransferase-GHRH associations and the small number of
      dopamine-beta-hydroxylase-GHRH juxtapositions suggest that the vast majority of
      the observed TH-GHRH juxtapositions represent dopaminergic associations. The
      density of the abutting TH-IR fibers on the surface of the GHRH perikarya
      suggests that these juxtapositions may be functional synapses, and thus, in
      addition to NPY, catecholamines may regulate GHRH secretion via direct synaptic
      mechanisms.

PMID- 21849534
TI  - Superior tactile abilities in the blind: is blindness required?

PMID- 21849535
TI  - Early prenatal stress epigenetically programs dysmasculinization in second
      generation offspring via the paternal lineage.
AB  - Studies have linked sex-biased neurodevelopmental disorders, including autism and
      schizophrenia, with fetal antecedents such as prenatal stress. Further, these
      outcomes can persist into subsequent generations, raising the possibility that
      aspects of heritability in these diseases involve epigenetic mechanisms.
      Utilizing a mouse model in which we previously identified a period in early
      gestation when stress results in dysmasculinized and stress-sensitive male
      offspring, we have examined programming effects in second-generation offspring of
      prenatally stressed (F2-S) or control (F2-C) sires. Examination of gene
      expression patterns during the perinatal sensitive period, when organizational
      gonadal hormones establish the sexually dimorphic brain, confirmed
      dysmasculinization in F2-S males, where genes important in neurodevelopment
      showed a female-like pattern. Analyses of the epigenomic miRNA environment
      detected significant reductions in miR-322, miR-574, and miR-873 in the F2-S male
      brain, levels that were again more similar to those of control females. Increased
      expression of a common gene target for these three miRNAs, beta-glycan, was
      confirmed in these males. These developmental effects were associated with the
      transmission of a stress-sensitive phenotype and shortened anogenital distance in
      adult F2-S males. As confirmation that the miRNA environment is responsive to
      organizational testosterone, neonatal males administered the aromatase inhibitor
      formestane exhibited dramatic changes in brain miRNA patterns, suggesting that
      miRNAs may serve a previously unappreciated role in organizing the sexually
      dimorphic brain. Overall, these data support the existence of a sensitive period
      of early gestation when epigenetic programming of the male germline can occur,
      permitting transmission of specific phenotypes into subsequent generations.

PMID- 21849536
TI  - APP is phosphorylated by TrkA and regulates NGF/TrkA signaling.
AB  - The pathogenic model of Alzheimer's disease (AD) posits that aggregates of
      amyloid beta, a product of amyloid precursor protein (APP) processing, cause
      dementia. However, alterations of normal APP functions could contribute to AD
      pathogenesis, and it is therefore important to understand the role of APP. APP is
      a member of a gene family that shows functional redundancy as documented by the
      evidence that single knock-out mice are viable, whereas mice with combined
      deletions of APP family genes die shortly after birth. A residue in the APP
      intracellular region, Y(682), is indispensable for these essential functions of
      APP. It is therefore important to identify pathways that regulate phosphorylation
      of Y(682) as well as the role of Y(682) in vivo. TrkA is associated with both
      phosphorylation of APP-Y(682) and alteration of APP processing, suggesting that
      tyrosine phosphorylation of APP links APP processing and neurotrophic signaling
      to intracellular pathways associated with cellular differentiation and survival.
      Here we have tested whether the NGF/TrkA signaling pathway is a physiological
      regulator of APP phosphorylation. We find that NGF induces tyrosine
      phosphorylation of APP, and that APP interacts with TrkA and this interaction
      requires Y(682). Unpredictably, we also uncover that APP, and specifically
      Y(682), regulates activation of the NGF/TrkA signaling pathway in vivo, the
      subcellular distribution of TrkA and the sensitivity of neurons to the trophic
      action of NGF. This evidence suggests that these two membrane protein's functions
      are strictly interconnected and that the NGF/TrkA signaling pathway is involved
      in AD pathogenesis and can be used as a therapeutic target.

PMID- 21849537
TI  - TrkB as a potential synaptic and behavioral tag.
AB  - Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory
      (LTM), requires de novo protein synthesis. An attractive hypothesis for synapse
      specificity of long-term memory is "synaptic tagging": synaptic activity
      generates a tag, which "captures" the PRPs (plasticity-related proteins) derived
      outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF
      (brain-derived neurotrophic factor), may serve as a "synaptic tag." TrkB is
      transiently activated by weak theta-burst stimulation (TBS) that induces only
      early-phase LTP (E-LTP). This TrkB activation is independent of protein
      synthesis, and confined to stimulated synapses. Induction of L-LTP by strong
      stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a
      second, independent pathway. Transient inhibition of TrkB around the time of weak
      TBS to the second pathway diminished L-LTP in that pathway without affecting the
      first one. Behaviorally, weak training, which induces short-term memory (STM) but
      not LTM, can be consolidated into LTM by exposing animals to novel but not
      familiar environment 1 h before training. Inhibition of TrkB during STM training
      blocked such consolidation. These results suggest TrkB as a potential tag for
      synapse-specific expression of L-LTP and LTM.

PMID- 21849538
TI  - Cellular-resolution population imaging reveals robust sparse coding in the
      Drosophila mushroom body.
AB  - Sensory stimuli are represented in the brain by the activity of populations of
      neurons. In most biological systems, studying population coding is challenging
      since only a tiny proportion of cells can be recorded simultaneously. Here we
      used two-photon imaging to record neural activity in the relatively simple
      Drosophila mushroom body (MB), an area involved in olfactory learning and memory.
      Using the highly sensitive calcium indicator GCaMP3, we simultaneously monitored
      the activity of >100 MB neurons in vivo (~5% of the total population). The MB is
      thought to encode odors in sparse patterns of activity, but the code has yet to
      be explored either on a population level or with a wide variety of stimuli. We
      therefore imaged responses to odors chosen to evaluate the robustness of sparse
      representations. Different odors activated distinct patterns of MB neurons;
      however, we found no evidence for spatial organization of neurons by either
      response probability or odor tuning within the cell body layer. The degree of
      sparseness was consistent across a wide range of stimuli, from monomolecular
      odors to artificial blends and even complex natural smells. Sparseness was mainly
      invariant across concentrations, largely because of the influence of recent odor
      experience. Finally, in contrast to sensory processing in other systems, no
      response features distinguished natural stimuli from monomolecular odors. Our
      results indicate that the fundamental feature of odor processing in the MB is to
      create sparse stimulus representations in a format that facilitates arbitrary
      associations between odor and punishment or reward.

PMID- 21849539
TI  - The general and outcome-specific forms of Pavlovian-instrumental transfer are
      differentially mediated by the nucleus accumbens core and shell.
AB  - Tests of Pavlovian-instrumental transfer (PIT) demonstrate that reward-predictive
      stimuli can exert a powerful motivational influence on the performance of
      instrumental actions. Recent evidence suggests that predictive stimuli produce
      this effect through either the general arousal (general PIT) or the specific
      predictions (outcome-specific PIT) produced by their association with reward. In
      two experiments, we examined the effects of pretraining lesions (Experiment 1) or
      muscimol-induced inactivation (Experiment 2) of either the core or shell regions
      of the nucleus accumbens (NAC) on these forms of PIT. Rats received Pavlovian
      training in which three auditory stimuli each predicted the delivery of a
      distinct food outcome. Separately, the rats were trained to perform two
      instrumental actions, each of which earned one of the outcomes used in Pavlovian
      conditioning. Finally, the effects of the three stimuli on performance of the two
      actions were assessed in extinction. Here we report evidence of a double
      dissociation between general and outcome-specific PIT at the level of the
      accumbens. Shell lesions eliminated outcome-specific PIT but spared general PIT,
      whereas lesions of the core abolished general PIT but spared outcome-specific
      PIT. Importantly, the infusion of muscimol into core or shell made immediately
      before the PIT tests produced a similar pattern of results. These results suggest
      that whereas the NAC core mediates the general excitatory effects of reward
      related cues, the NAC shell mediates the effect of outcome-specific reward
      predictions on instrumental performance, and thereby serve to clarify reported
      discrepancies regarding the role of the NAC core and shell in PIT.

PMID- 21849540
TI  - Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse
      model of spinocerebellar ataxia type 1.
AB  - The contribution of neuronal dysfunction to neurodegeneration is studied in a
      mouse model of spinocerebellar ataxia type 1 (SCA1) displaying impaired motor
      performance ahead of loss or atrophy of cerebellar Purkinje cells. Presymptomatic
      SCA1 mice show a reduction in the firing rate of Purkinje cells (both in vivo and
      in slices) associated with a reduction in the efficiency of the main
      glutamatergic synapse onto Purkinje cells and with increased A-type potassium
      current. The A-type potassium channel Kv4.3 appears to be internalized in
      response to glutamatergic stimulation in Purkinje cells and accumulates in
      presymptomatic SCA1 mice. SCA1 mice are treated with aminopyridines, acting as
      potassium channel blockers to test whether the treatment could improve neuronal
      dysfunction, motor behavior, and neurodegeneration. In acutely treated young SCA1
      mice, aminopyridines normalize the firing rate of Purkinje cells and the motor
      behavior of the animals. In chronically treated old SCA1 mice, 3,4
      diaminopyridine improves the firing rate of Purkinje cells, the motor behavior of
      the animals, and partially protects against cell atrophy. Chronic treatment with
      3,4-diaminopyridine is associated with increased cerebellar levels of BDNF,
      suggesting that partial protection against atrophy of Purkinje cells is possibly
      provided by an increased production of growth factors secondary to the reincrease
      in electrical activity. Our data suggest that aminopyridines might have
      symptomatic and/or neuroprotective beneficial effects in SCA1, that reduction in
      the firing rate of Purkinje cells can cause cerebellar ataxia, and that treatment
      of early neuronal dysfunction is relevant in neurodegenerative disorders such as
      SCA1.

PMID- 21849541
TI  - One week of motor adaptation induces structural changes in primary motor cortex
      that predict long-term memory one year later.
AB  - The neural bases of motor adaptation have been extensively explored in human and
      nonhuman primates. A network including the cerebellum, primary motor cortex, and
      posterior parietal cortex appears to be crucial for this type of learning. Yet,
      to date, it is unclear whether these regions contribute directly or indirectly to
      the formation of motor memories. Here we trained subjects on a complex visuomotor
      rotation associated with long-term memory (in the order of months) to identify
      potential sites of structural plasticity induced by adaptation. One week of
      training led to (1) an increment in local gray matter concentration over the hand
      area of the contralateral primary motor cortex and (2) an increase in fractional
      anisotropy in an area underneath this region that correlated with the speed of
      learning. Moreover, the change in gray matter concentration measured immediately
      after training predicted improvements in the speed of learning during
      readaptation 1 year later. Our study suggests that motor adaptation induces
      structural plasticity in primary motor circuits. In addition, it provides the
      first piece of evidence indicating that early structural changes induced by motor
      learning may impact on behavior up to 1 year after training.

PMID- 21849542
TI  - Regulation of temporal and spatial organization of newborn GnRH neurons by IGF
      signaling in zebrafish.
AB  - When and how newborn neurons are organized to form a functional network in the
      developing brain remains poorly understood. An attractive model is the
      gonadotropin-releasing hormone (GnRH) neuron system, master regulator of the
      reproductive axis. Here we show that blockage of IGF signaling, a central growth
      promoting signaling pathway, by the induced expression of a dominant-negative
      form of IGF1 receptor (IGF1R) or specific IGF1R inhibitors delayed the emergence
      of GnRH2 neurons in the midbrain and GnRH3 neurons in the olfactory bulb region.
      Blockage of IGF signaling also resulted in an abnormal appearance of GnRH3
      neurons outside of the olfactory bulb region, although it did not change the
      locations of other olfactory neurons, GnRH2 neurons, or brain patterning. This
      IGF action is developmental stage-dependent because the blockade of IGF signaling
      in advanced embryos had no such effect. An application of phosphatidylinositol 3
      kinase (PI3K) inhibitors phenocopied the IGF signaling deficient embryos, whereas
      the MAPK inhibitors had no effect, suggesting that this IGF action is mediated
      through the PI3K pathway. Real-time in vivo imaging studies revealed that the
      ectopic GnRH3 neurons emerged at the same time as the normal GnRH3 neurons in IGF
      deficient embryos. Further experiments suggest that IGF signaling affects the
      spatial distribution of newborn GnRH3 neurons by influencing neural crest cell
      migration and/or differentiation. These results suggest that the IGF-IGF1R-PI3K
      pathway regulates the precise temporal and spatial organization of GnRH neurons
      in zebrafish and provides new insights into the regulation of GnRH neuron
      development.

PMID- 21849543
TI  - Fasting and 17beta-estradiol differentially modulate the M-current in
      neuropeptide Y neurons.
AB  - Multiple K(+) conductances are targets for many peripheral and central signals
      involved in the control of energy homeostasis. Potential K(+) channel targets are
      the KCNQ subunits that form the channels underlying the M-current, a
      subthreshold, non-inactivating K(+) current that is a common target for G-protein
      coupled receptors. Whole-cell recordings were made from GFP (Renilla)-tagged
      neuropeptide Y (NPY) neurons from the arcuate nucleus of the hypothalamus using
      protocols to isolate and characterize the M-current in these orexigenic neurons.
      We recorded robust K(+) currents in the voltage range of the M-current, which
      were inhibited by the selective KCNQ channel blocker 10,10-bis(4-pyridinylmethyl)
      9(10H)-anthracenone dihydrochloride (XE991) (40 MUm), in both intact males and
      ovariectomized, 17beta-estradiol (E2)-treated females. Since NPY neurons are
      orexigenic and are active during fasting, the M-current was measured in fed and
      fasted male mice. Fasting attenuated the XE991-sensitive current by threefold,
      which correlated with decreased expression of the KCNQ2 and KCNQ3 subunits as
      measured with quantitative real-time PCR. Furthermore, E2 treatment augmented the
      XE991-sensitive M-current by threefold in ovariectomized (vs oil-treated) female
      mice. E2 treatment increased the expression of the KCNQ5 subunit in females but
      not KCNQ2 or KCNQ3 subunits. Fasting in females abrogated the effects of E2 on M
      current activity, at least in part, by decreasing KCNQ2 and KCNQ3 expression. In
      summary, these data suggest that the M-current plays a pivotal role in the
      modulation of NPY neuronal excitability and may be an important cellular target
      for neurotransmitter and hormonal signals in the control of energy homeostasis in
      both males and females.

PMID- 21849544
TI  - Spinal synthesis of estrogen and concomitant signaling by membrane estrogen
      receptors regulate spinal kappa- and MU-opioid receptor heterodimerization and
      female-specific spinal morphine antinociception.
AB  - We previously demonstrated that the spinal cord kappa-opioid receptor (KOR) and
      MU-opioid receptor (MOR) form heterodimers (KOR/MOR). KOR/MOR formation and the
      associated KOR dependency of spinal morphine antinociception are most robust
      during proestrus. Using Sprague Dawley rats, we now demonstrate that (1) spinal
      synthesis of estrogen is critical to these processes, and (2) blockade of either
      estrogen receptor (ER) alpha-, beta-, or G-protein-coupled ER1 or progesterone
      receptor (PR) substantially reduces KOR/MOR and eliminates mediation by KOR of
      spinal morphine antinociception. Effects of blocking ERs were manifest within 15
      min, whereas those of PR blockade were manifest after 18 h, indicating the
      requirement for rapid signaling by estrogen and transcriptional effects of
      progesterone. Individual or combined blockade of ERs produced the same magnitude
      of effect, suggesting that they work in tandem as part of a macromolecular
      complex to regulate KOR/MOR formation. Consistent with this inference, we found
      that KOR and MOR were coexpressed with ERalpha and G-protein-coupled ER1 in the
      spinal dorsal horn. Reduction of KOR/MOR by ER or PR blockade or spinal aromatase
      inhibition shifts spinal morphine antinociception from KOR dependent to KOR
      independent. This indicates a sex steroid-dependent plasticity of spinal KOR
      functionality, which could explain the greater analgesic potency of KOR agonists
      in women versus men. We suggest that KOR/MOR is a molecular switch that shifts
      the function of KOR and thereby endogenous dynorphin from pronociceptive to
      antinociceptive. KOR/MOR could thus serve as a novel molecular target for pain
      management in women.

PMID- 21849545
TI  - Determination of transmembrane water fluxes in neurons elicited by glutamate
      ionotropic receptors and by the cotransporters KCC2 and NKCC1: a digital
      holographic microscopy study.
AB  - Digital holographic microscopy (DHM) is a noninvasive optical imaging technique
      that provides quantitative phase images of living cells. In a recent study, we
      showed that the quantitative monitoring of the phase signal by DHM was a simple
      label-free method to study the effects of glutamate on neuronal optical responses
      (Pavillon et al., 2010). Here, we refine these observations and show that
      glutamate produces the following three distinct optical responses in mouse
      primary cortical neurons in culture, predominantly mediated by NMDA receptors:
      biphasic, reversible decrease (RD) and irreversible decrease (ID) responses. The
      shape and amplitude of the optical signal were not associated with a particular
      cellular phenotype but reflected the physiopathological status of neurons linked
      to the degree of NMDA activity. Thus, the biphasic, RD, and ID responses
      indicated, respectively, a low-level, a high-level, and an "excitotoxic" level of
      NMDA activation. Moreover, furosemide and bumetanide, two inhibitors of sodium
      coupled and/or potassium-coupled chloride movement strongly modified the phase
      shift, suggesting an involvement of two neuronal cotransporters, NKCC1 (Na-K-Cl)
      and KCC2 (K-Cl) in the genesis of the optical signal. This observation is of
      particular interest since it shows that DHM is the first imaging technique able
      to monitor dynamically and in situ the activity of these cotransporters during
      physiological and/or pathological neuronal conditions.

PMID- 21849546
TI  - The postnatal accumulation of junctional E-cadherin is inversely correlated with
      the capacity for supporting cells to convert directly into sensory hair cells in
      mammalian balance organs.
AB  - Mammals experience permanent impairments from hair cell (HC) losses, but birds
      and other non-mammals quickly recover hearing and balance senses after supporting
      cells (SCs) give rise to replacement HCs. Avian HC epithelia express little or no
      E-cadherin, and differences in the thickness of F-actin belts at SC junctions
      strongly correlate with different species' capacities for HC replacement, so we
      investigated junctional cadherins in human and murine ears. We found strong E
      cadherin expression at SC-SC junctions that increases more than sixfold
      postnatally in mice. When we cultured utricles from young mice with gamma
      secretase inhibitors (GSIs), striolar SCs completely internalized their E
      cadherin, without affecting N-cadherin. Hes and Hey expression also decreased and
      the SCs began to express Atoh1. After 48 h, those SCs expressed myosins VI and
      VIIA, and by 72 h, they developed hair bundles. However, some scattered striolar
      SCs retained E-cadherin and the SC phenotype. In extrastriolar regions, the vast
      majority of SCs also retained E-cadherin and failed to convert into HCs even
      after long GSI treatments. Microscopic measurements revealed that the junctions
      between extrastriolar SCs were more developed than those between striolar SCs. In
      GSI-treated utricles as old as P12, differentiated striolar SCs converted into
      HCs, but such responses declined with age and ceased by P16. Thus, temporal and
      spatial differences in postnatal SC-to-HC phenotype conversion capacity are
      linked to the structural attributes of E-cadherin containing SC junctions in
      mammals, which differ substantially from their counterparts in non-mammalian
      vertebrates that readily recover from hearing and balance deficits through hair
      cell regeneration.

PMID- 21849547
TI  - Extra-classical tuning predicts stimulus-dependent receptive fields in auditory
      neurons.
AB  - The receptive fields of many sensory neurons are sensitive to statistical
      differences among classes of complex stimuli. For example, excitatory spectral
      bandwidths of midbrain auditory neurons and the spatial extent of cortical visual
      neurons differ during the processing of natural stimuli compared to the
      processing of artificial stimuli. Experimentally characterizing neuronal
      nonlinearities that contribute to stimulus-dependent receptive fields is
      important for understanding how neurons respond to different stimulus classes in
      multiple sensory modalities. Here we show that in the zebra finch, many auditory
      midbrain neurons have extra-classical receptive fields, consisting of sideband
      excitation and sideband inhibition. We also show that the presence, degree, and
      asymmetry of stimulus-dependent receptive fields during the processing of complex
      sounds are predicted by the presence, valence, and asymmetry of extra-classical
      tuning. Neurons for which excitatory bandwidth expands during the processing of
      song have extra-classical excitation. Neurons for which frequency tuning is
      static and for which excitatory bandwidth contracts during the processing of song
      have extra-classical inhibition. Simulation experiments further demonstrate that
      stimulus-dependent receptive fields can arise from extra-classical tuning with a
      static spike threshold nonlinearity. These findings demonstrate that a common
      neuronal nonlinearity can account for the stimulus dependence of receptive fields
      estimated from the responses of auditory neurons to stimuli with natural and non
      natural statistics.

PMID- 21849549
TI  - The phase of ongoing oscillations mediates the causal relation between brain
      excitation and visual perception.
AB  - Why does neuronal activity in sensory brain areas sometimes give rise to
      perception, and sometimes not? Although neuronal noise is often invoked as the
      key factor, a portion of this variability could also be due to the history and
      current state of the brain affecting cortical excitability. Here we directly test
      this idea by examining whether the phase of prestimulus oscillatory activity is
      causally linked with modulations of cortical excitability and with visual
      perception. Transcranial magnetic stimulation (TMS) was applied over human visual
      cortex to induce illusory perceptions (phosphenes) while electroencephalograms
      (EEGs) were simultaneously recorded. Subjects reported the presence or absence of
      an induced phosphene following a single pulse of TMS at perceptual threshold. The
      phase of ongoing alpha (~10 Hz) oscillations within 400 ms before the pulse
      significantly covaried with the perceptual outcome. This effect was observed in
      occipital regions around the site of TMS, as well as in a distant frontocentral
      region. In both regions, we found a systematic relationship between prepulse EEG
      phase and perceptual performance: phosphene probability changed by ~15% between
      opposite phases. In summary, we provide direct evidence for a chain of causal
      relations between the phase of ongoing oscillations, neuronal excitability, and
      visual perception: ongoing oscillations create periodic "windows of
      excitability," with sensory perception being more likely to occur at specific
      phases.

PMID- 21849548
TI  - Regulator of G-protein signaling-10 negatively regulates NF-kappaB in microglia
      and neuroprotects dopaminergic neurons in hemiparkinsonian rats.
AB  - Microglia are the brain-resident macrophages responsible for immune surveillance
      that become activated in response to injury, infection, environmental toxins, and
      other stimuli that threaten neuronal survival. Previous work from our group
      demonstrated that mice deficient in Regulator of G-protein Signaling 10 (RGS10),
      a microglia-enriched GTPase activating protein (GAP) for G-protein alpha
      subunits, displayed increased microglial burden in the CNS at birth and developed
      a parkinsonian phenotype after exposure to chronic systemic inflammation,
      implicating a neuroprotective role for RGS10 in the nigrostriatal pathway. While
      it is known that RGS10 is expressed in both microglia and certain subsets of
      neurons, it is not known whether RGS10 functions similarly in both cells types.
      In this study we sought to delineate the specific role of RGS10 in microglia and
      identify the molecular pathway(s) required for RGS10 to exert its actions in
      microglia. Here, we identify RGS10 as a negative regulator of the nuclear factor
      kappaB(NF-kappaB) pathway in microglia and demonstrate that the proinflammatory
      and cytotoxic phenotype of Rgs10-null microglia can be reversed by lentiviral
      mediated restoration of RGS10 expression. In vivo gene transfer of RGS10 into the
      substantia nigra pars compacta (SNpc) of rats reduced microgliosis and protected
      against 6-OHDA neurotoxin-induced death of dopaminergic (DA) neurons. Together,
      our findings suggest that modulation of RGS10 activity in microglia may afford
      therapeutic benefit in the treatment of chronic neuroinflammatory conditions as
      well as neuroprotection against inflammation-related degeneration in Parkinson's
      disease (PD), the second most common neurodegenerative disorder affecting
      individuals over age 65.

PMID- 21849550
TI  - TrkB and protein kinase Mzeta regulate synaptic localization of PSD-95 in
      developing cortex.
AB  - Postsynaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is
      critical for synapse maturation and learning. In rodents, eye opening, the onset
      of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata
      to synapses. We showed previously that the PI3 kinase-Akt pathway downstream of
      BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular
      transport. However, vesicular transport requires PSD-95 palmitoylation to attach
      it to a lipid membrane. Also, PSD-95 insertion at synapses is known to require
      this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary
      for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical
      layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of
      another pathway downstream of BDNF/TrkB, namely, signaling through phospholipase
      Cgamma and the brain-specific PKC variant protein kinase M zeta (PKMzeta). We
      find that PKMzeta selectively regulates phosphorylation of the palmitoylation
      enzyme ZDHHC8. Inhibition of PKMzeta results in a reduction of synaptic PSD-95
      accumulation in vivo, which can be rescued by overexpressing ZDHHC8. Therefore,
      TrkB and PKMzeta, two critical regulators of synaptic plasticity, facilitate PSD
      95 targeting to synapses. These results also indicate that palmitoylation can be
      regulated by a trophic factor. Our findings have implications for
      neurodevelopmental disorders as well as aging brains.

PMID- 21849551
TI  - Fas-associated factor 1 as a regulator of olfactory axon guidance.
AB  - Axon guidance is a crucial part of neural circuit formation. While precise axonal
      targeting forms the basis of accurate information delivery, the mechanisms that
      regulate this process are still unclear. Apoptotic signaling molecules have been
      identified in the axon terminal, but their specific role in axon guidance is not
      well understood. Here we use the mouse olfactory system as an in vivo model to
      demonstrate that by modulating Fas-associated factor 1 (FAF1), an apoptosis
      regulatory molecule, we can rewire axonal projections. Interestingly, FAF1 is
      highly expressed in the developing mouse olfactory system, but its expression is
      downregulated postnatally. Using a tetracycline-inducible promoter Tet-Off
      system, we generated transgenic mice in which FAF1 is specifically expressed in
      immature olfactory sensory neurons (OSNs) and show that overexpression of FAF1
      not only misroutes OSN axons to deep layers of the olfactory bulb but also leads
      to widespread disruption of the glomerular layer. In addition, we also
      demonstrate that the specific convergence of P2 receptor OSN axons is completely
      distorted in the FAF1 mice. Strikingly, all of the mutant phenotypes can be
      recovered by shutting down FAF1 expression through the administration of
      doxycycline. Together, our study provides clear in vivo evidence that an
      apoptotic molecule can indeed regulate axon targeting and that OSNs can restore
      their organization even after broad disruption.

PMID- 21849553
TI  - Dynamics of executive control and motor deficits in parkinsonian rats.
AB  - While there is general agreement that in Parkinson's disease (PD), striatal
      dopamine (DA) depletion causes motor deficits, the origin of the associated
      cognitive impairments remains a matter of debate. The present study aimed to
      decipher the influence of a partial 6-hydroxydopamine (6-OHDA) lesion of striatal
      DA nerve terminals in rats performing a reaction time task previously used to
      assess cognitive deficits in PD patients. The effects of two behavioral
      manipulations-foreperiod duration and stimulus-response congruence-known to
      affect motor processes and executive control, respectively, were studied over 8
      weeks postsurgery in control and lesion animals. Two weeks after surgery, the
      lesion abolished the effect of foreperiod, confirming the direct involvement of
      striatal DA in motor processes, but failed to alter the effect of congruence.
      During the following weeks, the effect of foreperiod was reinstated, indicating a
      recovery of lesion-induced motor symptoms. This recovery was accompanied by a
      progressive increase of the congruence effect, signaling an executive control
      deficit in lesion animals. This result provides the first evidence that 6-OHDA
      lesioned rats exhibit the same cognitive impairment as PD patients in this task.
      The deficit, however, built up progressively after the lesion and may result from
      adaptations mitigating lesion-induced motor deficits.

PMID- 21849552
TI  - Macroglial plasticity and the origins of reactive astroglia in experimental
      autoimmune encephalomyelitis.
AB  - Accumulations of hypertrophic, intensely glial fibrillary acidic protein-positive
      (GFAP(+)) astroglia, which also express immunoreactive nestin and vimentin, are
      prominent features of multiple sclerosis lesions. The issues of the cellular
      origin of hypertrophic GFAP(+)/vimentin(+)/nestin(+) "reactive" astroglia and
      also the plasticities and lineage relationships among three macroglial progenitor
      populations-oligodendrocyte progenitor cells (OPCs), astrocytes and ependymal
      cells-during multiple sclerosis and other CNS diseases remain controversial. We
      used genetic fate-mappings with a battery of inducible Cre drivers (Olig2-Cre
      ER(T2), GFAP-Cre-ER(T2), FoxJ1-Cre-ER(T2) and Nestin-Cre-ER(T2)) to explore these
      issues in adult mice with myelin oligodendrocyte glycoprotein peptide-induced
      experimental autoimmune encephalomyelitis (EAE). The proliferative rate of spinal
      cord OPCs rose fivefold above control levels during EAE, and numbers of
      oligodendroglia increased as well, but astrogenesis from OPCs was rare. Spinal
      cord ependymal cells, previously reported to be multipotent, did not augment
      their low proliferative rate, nor give rise to astroglia or OPCs. Instead, the
      hypertrophic, vimentin(+)/nestin(+), reactive astroglia that accumulated in
      spinal cord in this multiple sclerosis model were derived by proliferation and
      phenotypic transformation of fibrous astroglia in white matter, and solely by
      phenotypic transformation of protoplasmic astroglia in gray matter. This
      comprehensive analysis of macroglial plasticity in EAE helps to clarify the
      origins of astrogliosis in CNS inflammatory demyelinative disorders.

PMID- 21849554
TI  - Downregulation of the posterior medial frontal cortex prevents social conformity.
AB  - We often change our behavior to conform to real or imagined group pressure.
      Social influence on our behavior has been extensively studied in social
      psychology, but its neural mechanisms have remained largely unknown. Here we
      demonstrate that the transient downregulation of the posterior medial frontal
      cortex by theta-burst transcranial magnetic stimulation reduces conformity, as
      indicated by reduced conformal adjustments in line with group opinion. Both the
      extent and probability of conformal behavioral adjustments decreased
      significantly relative to a sham and a control stimulation over another brain
      area. The posterior part of the medial frontal cortex has previously been
      implicated in behavioral and attitudinal adjustments. Here, we provide the first
      interventional evidence of its critical role in social influence on human
      behavior.

PMID- 21849555
TI  - Oxygen/glucose deprivation induces a reduction in synaptic AMPA receptors on
      hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors.
AB  - Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage,
      whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed
      that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in
      vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced
      permeability of AMPARs to Ca(2+), resulting in delayed cell death. However, it is
      unclear whether the same mechanisms exist in CA3 neurons and whether this
      underlies the differential sensitivity to ischemia. Here, we investigated the
      consequences of OGD for AMPAR function in CA3 neurons using electrophysiological
      recordings in rat hippocampal slices. Following a 15 min OGD protocol, a
      substantial depression of AMPAR-mediated synaptic transmission was observed at
      CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer
      collateral synapses. The depression of synaptic transmission following OGD was
      prevented by metabotropic glutamate receptor 1 (mGluR1) or A(3) receptor
      antagonists, indicating a role for both glutamate and adenosine release.
      Inhibition of PLC, PKC, or chelation of intracellular Ca(2+) also prevented the
      depression of synaptic transmission. Inclusion of peptides to interrupt the
      interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the
      depression of transmission, suggesting a dynamin and PICK1-dependent
      internalization of AMPARs after OGD. We also show that a reduction in surface and
      total AMPAR protein levels after OGD was prevented by mGluR1 or A(3) receptor
      antagonists, indicating that AMPARs are degraded following internalization. Thus,
      we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons
      following OGD that has the potential to reduce excitotoxicity and promote
      neuroprotection.

PMID- 21849556
TI  - ERK2 contributes to the control of social behaviors in mice.
AB  - Signaling through extracellular signal-regulated kinase (ERK) is important in
      multiple signal transduction networks in the CNS. However, the specific role of
      ERK2 in in vivo brain functions is not fully understood. Here we show that ERK2
      play a critical role in regulating social behaviors as well as cognitive and
      emotional behaviors in mice. To study the brain function of ERK2, we used a
      conditional, region-specific, genetic approach to target Erk2 using the Cre/loxP
      strategy with a nestin promoter-driven cre transgenic mouse line to induce
      recombination in the CNS. The resulting Erk2 conditional knock-out (CKO) mice, in
      which Erk2 was abrogated specifically in the CNS, were viable and fertile with a
      normal appearance. These mice, however, exhibited marked anomalies in multiple
      aspects of social behaviors related to facets of autism-spectrum disorders:
      elevated aggressive behaviors, deficits in maternal nurturing, poor nest
      building, and lower levels of social familiarity and social interaction. Erk2 CKO
      mice also exhibited decreased anxiety-related behaviors and impaired long-term
      memory. Pharmacological inhibition of ERK1 phosphorylation in Erk2 CKO mice did
      not affect the impairments in social behaviors and learning disabilities,
      indicating that ERK2, but not ERK1 plays a critical role in these behaviors. Our
      findings suggest that ERK2 has complex and multiple roles in the CNS, with
      important implications for human psychiatric disorders characterized by deficits
      in social behaviors.

PMID- 21849557
TI  - Descending corticospinal control of intersegmental dynamics.
AB  - To make an accurate movement, the CNS has to overcome the inherent complexities
      of the multijoint limb. For example, interaction torques arise when motion of
      individual arm segments propagates to adjacent segments causing their movement
      without any muscle contractions. Since these passive joint torques significantly
      add to the overall torques generated by active muscular contractions, they must
      be taken into account during planning or execution of goal-directed movements. We
      investigated the role of the corticospinal tract in compensating for the
      interaction torques during arm movements in humans. Twelve subjects reached to
      visual targets with their arm supported by a robotic exoskeleton. Reaching to one
      target was accompanied by interaction torques that assisted the movement, while
      reaching to the other target was accompanied by interaction torques that resisted
      the movement. Corticospinal excitability was assessed at different times during
      movement using single-pulse transcranial magnetic stimulation (TMS) over the
      upper-arm region of M1 (primary motor cortex). We found that TMS responses in
      shoulder monoarticular and elbow-shoulder biarticular muscles changed together
      with the interaction torques during movements in which the interaction torques
      were resistive. In contrast, TMS responses did not correlate with assistive
      interaction torques or with co-contraction. This suggests that the descending
      motor command includes compensation for passive limb dynamics. Furthermore, our
      results suggest that compensation for interaction torques involves the
      biarticular muscles, which span both shoulder and elbow joints and are in a
      biomechanically advantageous position to provide such compensation.

PMID- 21849558
TI  - Palmitoyl acyltransferase zD17 mediates neuronal responses in acute ischemic
      brain injury by regulating JNK activation in a signaling module.
AB  - Although the palmitoyl acyltransferase (PAT) zinc-finger DHHC containing 17
      (zD17) has been implicated in genetic neurological disorders by regulating
      protein palmitoylation, the role of zD17 in acute brain injury remains unknown.
      Here, we report that zD17 contributes to acute ischemic brain injury via a
      mechanism independent of its PAT activity. We have found that zD17 directly
      interacts with c-Jun N terminus kinase (JNK) to form a signaling module for JNK
      activation. Pathological stressors induce the zD17-JNK interaction, which
      promotes downstream neuronal cell death signals. We have developed novel peptides
      targeting the JNK-interacting motif on zD17 to selectively block the enhancement
      of the zD17-JNK interaction and the activation of JNK isoforms 2 and 3.
      Application of these peptides successfully blocks JNK activation and neuronal
      cell death pathways, protects cultured neurons from excitotoxicity, and
      dramatically reduces brain damage and behavioral deficits in a rat model of focal
      ischemic stroke. Our findings indicate zD17 as a key player in ischemic stroke
      and suggest the potential therapeutic value of targeting the zD17-JNK interaction
      for acute brain injury.

PMID- 21849560
TI  - The control of mimicry by eye contact is mediated by medial prefrontal cortex.
AB  - Spontaneous mimicry of other people's actions serves an important social
      function, enhancing affiliation and social interaction. This mimicry can be
      subtly modulated by different social contexts. We recently found behavioral
      evidence that direct eye gaze rapidly and specifically enhances mimicry of
      intransitive hand movements (Wang et al., 2011). Based on past findings linking
      medial prefrontal cortex (mPFC) to both eye contact and the control of mimicry,
      we hypothesized that mPFC might be the neural origin of this behavioral effect.
      The present study aimed to test this hypothesis. During functional magnetic
      resonance imaging (fMRI) scanning, 20 human participants performed a simple
      mimicry or no-mimicry task, as previously described (Wang et al., 2011), with
      direct gaze present on half of the trials. As predicted, fMRI results showed that
      performing the task activated mirror systems, while direct gaze and inhibition of
      the natural tendency to mimic both engaged mPFC. Critically, we found an
      interaction between mimicry and eye contact in mPFC, superior temporal sulcus
      (STS) and inferior frontal gyrus. We then used dynamic causal modeling to
      contrast 12 possible models of information processing in this network. Results
      supported a model in which eye contact controls mimicry by modulating the
      connection strength from mPFC to STS. This suggests that mPFC is the originator
      of the gaze-mimicry interaction and that it modulates sensory input to the mirror
      system. Thus, our results demonstrate how different components of the social
      brain work together to on-line control mimicry according to the social context.

PMID- 21849559
TI  - Small heat shock proteins induce a cerebral inflammatory reaction.
AB  - More than 80% of Alzheimer's disease (AD) patients have some degree of cerebral
      amyloid angiopathy (CAA). In addition to arteries and veins, capillaries can also
      be affected. Capillary CAA (capCAA), rather than CAA in larger vessels, is
      associated with flame-like amyloid-beta (Abeta) deposits that may extend beyond
      the vessel wall and radiate into the neuropil, a phenomenon also known as
      "dyshoric angiopathy." Abeta deposits in AD, parenchymal as well as (cap)CAA and
      dyshoric angiopathy, are associated with a local inflammatory reaction, including
      activation of microglial cells and astrocytes that, among others, produce
      cytokines and reactive oxygen species. This neuroinflammatory reaction may
      account for at least part of the cognitive decline. In previous studies we
      observed that small heat shock proteins (sHsps) are associated with Abeta
      deposits in AD. In this study the molecular chaperones Hsp20, HspB8 and HspB2B3
      were found to colocalize with CAA and capCAA in AD brains. In addition, Hsp20,
      HspB8 and HspB2B3 colocalized with intercellular adhesion molecule 1 (ICAM-1) in
      capCAA-associated dyshoric angiopathy. Furthermore, we demonstrated that Hsp20,
      HspB8 and HspB2B3 induced production of interleukin 8, soluble ICAM-1 and
      monocyte chemoattractant protein 1 by human leptomeningeal smooth muscle cells
      and human brain astrocytes in vitro and that Hsp27 inhibited production of
      transforming growth factor beta 1 and CD40 ligand. Our results suggest a central
      role for sHsps in the neuroinflammatory reaction in AD and CAA and thus in
      contributing to cognitive decline.

PMID- 21849561
TI  - Dual regulation of anterograde and retrograde transmission by endocannabinoids.
AB  - Endocannabinoids (eCBs) are feedback messengers in the nervous system that act at
      the presynaptic nerve terminal to inhibit transmitter release. Here we report
      that in brain slices from rat, eCBs are released from vasopressin (VP) neurons in
      the paraventricular nucleus of the hypothalamus following coincident bursts of
      presynaptic and postsynaptic spiking. eCBs transiently depress glutamate release
      from excitatory terminals and, in doing so, prevent the synapses from undergoing
      long-term depression (LTD). Specifically, we show that blockade of CB1 receptors
      unmasks LTD following coincident presynaptic and postsynaptic activity. This LTD
      is presynaptic in nature, but requires the release of the opioid peptide
      dynorphin from the postsynaptic neuron. Dynorphin release and subsequent LTD
      require the activation of postsynaptic metabotropic glutamate receptors (mGluRs).
      Our findings indicate that eCBs, by transiently depressing glutamate release,
      limit mGluR activation and indirectly gate release of dynorphin from the
      postsynaptic neuron. We propose that eCBs, in addition to their well described
      role in the rapid modulation of transmitter release from the nerve terminal, also
      regulate the release of other retrograde transmitters and thus encode for
      multiple temporal windows of synaptic plasticity.

PMID- 21849562
TI  - Associative learning increases trial-by-trial similarity of BOLD-MRI patterns.
AB  - Associative learning is a dynamic process that allows us to incorporate new
      knowledge within existing semantic networks. Even after years, a seemingly stable
      association can be altered by a single significant experience. Here, we
      investigate whether the acquisition of new associations affects the neural
      representation of stimuli and how the brain categorizes stimuli according to
      preexisting and emerging associations. Functional MRI data were collected during
      a differential fear conditioning procedure and at test (4-5 weeks later). Two
      pictures of faces and two pictures of houses served as stimuli. One of each pair
      coterminated with a shock in half of the trials (partial reinforcement). Applying
      Multivoxel Pattern Analysis (MVPA) in a trial-by-trial manner, we quantified
      changes in the similarity of neural representations of stimuli over the course of
      conditioning. Our findings show an increase in similarity of neural patterns
      throughout the cortex on consecutive trials of the reinforced stimuli.
      Furthermore, neural pattern similarity reveals a shift from original categories
      (faces/houses) toward new categories (reinforced/unreinforced) over the course of
      conditioning. This effect was differentially represented in the cortex, with
      visual areas primarily reflecting similarity of low-level stimulus properties
      (original categories) and frontal areas reflecting similarity of stimulus
      significance (new categories). Effects were not dependent on overall response
      amplitude and were still present during follow-up. We conclude that trial-by
      trial MVPA is a useful tool for examining how the human brain encodes relevant
      associations and forms new associative networks.

PMID- 21849563
TI  - Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons.
AB  - Cyclin-dependent kinase 5 (Cdk5) and its activator p35 have been implicated in
      drug addiction, neurodegenerative diseases such as Alzheimer's, learning and
      memory, and synapse maturation and plasticity. However, the molecular mechanisms
      by which Cdk5 regulates synaptic plasticity are still unclear. PSD-95 is a major
      postsynaptic scaffolding protein of glutamatergic synapses that regulates
      synaptic strength and plasticity. PSD-95 is ubiquitinated by the ubiquitin E3
      ligase Mdm2, and rapid and transient PSD-95 ubiquitination has been implicated in
      NMDA receptor-induced AMPA receptor endocytosis. Here we demonstrate that genetic
      or pharmacological reduction of Cdk5 activity increases the interaction of Mdm2
      with PSD-95 and enhances PSD-95 ubiquitination without affecting PSD-95 protein
      levels in vivo in mice, suggesting a nonproteolytic function of ubiquitinated PSD
      95 at synapses. We show that PSD-95 ubiquitination correlates with increased
      interaction with beta-adaptin, a subunit of the clathrin adaptor protein complex
      AP-2. This interaction is increased by genetic reduction of Cdk5 activity or NMDA
      receptor stimulation and is dependent on Mdm2. Together these results support a
      function for Cdk5 in regulating PSD-95 ubiquitination and its interaction with AP
      2 and suggest a mechanism by which PSD-95 may regulate NMDA receptor-induced AMPA
      receptor endocytosis.

PMID- 21849564
TI  - Representation of vestibular and visual cues to self-motion in ventral
      intraparietal cortex.
AB  - Convergence of vestibular and visual motion information is important for self
      motion perception. One cortical area that combines vestibular and optic flow
      signals is the ventral intraparietal area (VIP). We characterized unisensory and
      multisensory responses of macaque VIP neurons to translations and rotations in
      three dimensions. Approximately one-half of VIP cells show significant
      directional selectivity in response to optic flow, one-half show tuning to
      vestibular stimuli, and one-third show multisensory responses. Visual and
      vestibular direction preferences of multisensory VIP neurons could be congruent
      or opposite. When visual and vestibular stimuli were combined, VIP responses
      could be dominated by either input, unlike the medial superior temporal area
      (MSTd) where optic flow tuning typically dominates or the visual posterior
      sylvian area (VPS) where vestibular tuning dominates. Optic flow selectivity in
      VIP was weaker than in MSTd but stronger than in VPS. In contrast, vestibular
      tuning for translation was strongest in VPS, intermediate in VIP, and weakest in
      MSTd. To characterize response dynamics, direction-time data were fit with a
      spatiotemporal model in which temporal responses were modeled as weighted sums of
      velocity, acceleration, and position components. Vestibular responses in VIP
      reflected balanced contributions of velocity and acceleration, whereas visual
      responses were dominated by velocity. Timing of vestibular responses in VIP was
      significantly faster than in MSTd, whereas timing of optic flow responses did not
      differ significantly among areas. These findings suggest that VIP may be proximal
      to MSTd in terms of vestibular processing but hierarchically similar to MSTd in
      terms of optic flow processing.

PMID- 21849566
TI  - 'The good that is interred in their bones': are there property rights in the
      child?
AB  - Bone marrow donation between siblings is a common medical procedure. In some
      instances, the donor will be a young child incapable of providing either consent
      or assent, and the intervention is made lawful through the consent of the
      parent(s). Although a number of justifications have been formulated to cover this
      act with legitimacy, these fail to describe accurately the transaction that takes
      place. In the absence of the child authorising his parents to act as his proxy,
      it is unclear why parental consent is sufficient to permit the redistribution of
      his biological wealth. Instead, where the donor is such a young child, the whole
      procedure may be construed as the appropriation of bodily tissue from one
      unconsenting human and its conveyance to a third, albeit related, party. This
      paper argues that if the parentally authorised transfer of biological material
      from an unconsenting human to another is legally permissible, it must be on the
      basis of an implicitly acknowledged property right in the child.

PMID- 21849567
TI  - Conjoined twins as persons that can be victims of homicide.

PMID- 21849565
TI  - Munc13-1 is required for presynaptic long-term potentiation.
AB  - Long-lasting forms of synaptic plasticity involve modification of presynaptic
      strength in many brain regions. Although a presynaptic site for expression is
      well established, the detailed molecular mechanisms that lead to sustained
      changes in neurotransmitter release remain unclear. Here, we use acute in vivo
      genetic manipulation of synaptic proteins to investigate the molecular basis for
      presynaptic long-term potentiation (LTP) at hippocampal mossy fiber synapses.
      Munc13 proteins are active zone proteins that are essential for synaptic vesicle
      priming and neurotransmitter release. Munc13 proteins also interact with
      RIM1alpha, an active zone protein required for presynaptic long-term plasticity.
      By taking advantage of the observation that the RIM-binding domain of Munc13 is
      separable from the domain that is required for neurotransmitter release, we
      selectively tested whether Munc13-1 is an effector for RIM1alpha in presynaptic
      LTP. Our results provide the first evidence for the involvement of Munc13-1 in
      presynaptic long-term synaptic plasticity. We further demonstrate that the
      interaction between RIM1alpha and Munc13-1 is required for this plasticity. These
      results advance our understanding of the molecular mechanisms of presynaptic
      plasticity and suggest that modulation of vesicle priming may provide the
      cellular substrate for expression of LTP at mossy fiber synapses.

PMID- 21849568
TI  - A, B, and C leads to D (for delegation!). A, B and C v. Ireland 25579/05 [2010]
      ECHR 2032.

PMID- 21849570
TI  - Wild-type MIC distributions must be considered to set clinically meaningful
      susceptibility testing breakpoints for all bacterial pathogens, including
      Mycobacterium tuberculosis.

PMID- 21849571
TI  - Low prevalence of blaOXA-143 in private hospitals in Brazil.

PMID- 21849572
TI  - Continuous infusion may improve the efficacy of vancomycin in treatment of
      experimental endocarditis due to heterogeneous vancomycin-intermediate
      Staphylococcus aureus.

PMID- 21849589
TI  - Modelling the impacts of pests on forest productivity: a pathway through
      complexities and conundrums.

PMID- 21849590
TI  - Spur behaviour in almond trees: relationships between previous year spur leaf
      area, fruit bearing and mortality.
AB  - In mature almond (Prunus dulcis) orchards, the majority of crop is borne on spurs
      (short, proleptic shoots) that can live for several years and can produce from
      one to five fruits. Previous research has led to the hypothesis that spur
      longevity is related to spur light exposure, cropping and age. However, limited
      quantitative data are available to substantiate these hypotheses. The objective
      of this study was to determine spur characteristics that were most highly
      correlated with spur productivity and longevity in mature, bearing almond trees.
      Previous year spur leaf area was strongly related to spur viability and
      flowering; the greater the leaf area in the previous year, the higher the
      probability of spur survival into the next year and the higher the probability
      for the spur to bear one or more flowers. Previous year bearing also appeared to
      influence viability and return bloom, especially in spurs with low leaf area.
      These results suggest that spur source-sink balance is basic to the life cycle of
      almond spurs. Furthermore, the results are consistent with the hypothesis that
      spurs are semi-autonomous organs with respect to carbohydrate balance for much of
      the growing season. Finally, this information provides general thresholds for
      maintaining spur viability and productivity that will be useful for developing
      and evaluating tree training systems and orchard management practices.

PMID- 21849591
TI  - Effect of nitrogen fertilizer, root branch order and temperature on respiration
      and tissue N concentration of fine roots in Larix gmelinii and Fraxinus
      mandshurica.
AB  - Root respiration is closely related to root morphology, yet it is unclear
      precisely how to distinguish respiration-related root physiological functions
      within the branching fine root system. Root respiration and tissue N
      concentration were examined for different N fertilization treatments, sampling
      dates, branch orders and temperatures of larch (Larix gmelinii L.) and ash
      (Fraxinus mandshurica L.) using the excised roots method. The results showed that
      N fertilization enhanced both root respiration and tissue N concentration for all
      five branch orders. The greatest increases in average root respiration for N
      fertilization treatment were 13.30% in larch and 18.25% in ash at 6 degrees C.
      However, N fertilization did not change the seasonal dynamics of root
      respiration. Both root respiration and root tissue N concentration decreased with
      increase in root branch order. First-order (finest) roots exhibited the highest
      respiration rates and tissue N concentrations out of the five root branch orders
      examined. There was a highly significant linear relationship between fine root N
      concentration and root respiration rate. Root N concentration explained >60% of
      the variation in respiration rate at any given combination of root order and
      temperature. Root respiration showed a classical exponential relationship with
      temperature, with the Q(10) for root respiration in roots of different branching
      orders ranging from 1.62 to 2.20. The variation in root respiration by order
      illustrates that first-order roots are more metabolically active, suggesting that
      roots at different branch order positions have different physiological functions.
      The highly significant relationship between root respiration at different branch
      orders and root tissue N concentration suggests that root tissue N concentration
      may be used as a surrogate for root respiration, simplifying future research into
      the C dynamics of rooting systems.

PMID- 21849592
TI  - How does P affect photosynthesis and metabolite profiles of Eucalyptus globulus?
AB  - Phosphorus (P) has multiple effects on plant metabolism, but there are many
      unresolved questions especially for evergreen trees. For example, we do not know
      the general effects of P on metabolism, or if P affects photosynthesis via the
      internal conductance to CO(2) transfer from sub-stomatal cavities to chloroplast
      or amounts of Rubisco. This study investigates how P deficiency affects seedlings
      of the evergreen tree Eucalyptus globulus grown for 2.5 months with four nutrient
      solutions differing in P concentration. To determine why photosynthesis was
      affected by P supply, Rubisco was quantified by capillary electrophoresis,
      internal conductance was quantified from gas exchange and carbon isotope
      discrimination, and biochemical parameters of photosynthesis were estimated from
      A/C(c) responses. Additional insights into the effect of P on metabolism were
      provided by gas chromatography-mass spectrometry (GC-MS) metabolite profiling.
      Larger concentrations of P in the nutrient solution led to significantly faster
      rates of photosynthesis. There was no evidence that stomatal or internal
      conductances contributed to the effect of P supply on photosynthesis. The
      increase in photosynthesis with P supply was correlated with V(cmax), and amounts
      of P, phosphate and fructose 6-phosphate (6-P). Phosphorous supply affected
      approximately one-third of the 90 aqueous metabolites quantified by GC-MS, but
      the effect size was generally smaller than reported for experiments on herbaceous
      species. Phosphorus deficiency decreased concentrations of phosphate, glucose 6-P
      and fructose 6-P more than it decreased photosynthesis, suggesting faster
      turnover of smaller pools of phosphate and phosphorylated intermediates. The
      effect of P supply on most amino acids was small, with the exception of arginine
      and glutamine, which increased dramatically under P deficiency. P deficiency had
      small or non-significant effects on carbohydrates and organic acids of the
      tricarboxylic acid (TCA) cycle. The small effect of P on carbohydrates, organic
      acids and (most) amino acids likely reflects a functional homeostasis among C
      metabolism (glycolysis, TCA and pentose P cycles), rates of photosynthesis and
      growth. The strong functional homeostasis in E. globulus may reflect a
      conservative, long-term growth and metabolic strategy of evergreen trees.

PMID- 21849593
TI  - Leaf gas exchange in the frankincense tree (Boswellia papyrifera) of African dry
      woodlands.
AB  - A conceptual model was tested for explaining environmental and physiological
      effects on leaf gas exchange in the deciduous dry tropical woodland tree
      Boswellia papyrifera (Del.) Hochst. For this species we aimed at (i)
      understanding diurnal patterns in leaf gas exchange, (ii) exploring cause-effect
      relationships among external environment, internal physiology and leaf gas
      exchange, and (iii) exploring site differences in leaf gas exchange in response
      to environmental variables. Diurnal courses in gas exchange, underlying
      physiological traits and environmental variables were measured for 90 trees on
      consecutive days at two contrasting areas, one at high and the other at low
      altitude. Assimilation was highest in the morning and slightly decreased during
      the day. In contrast, transpiration increased from early morning to midday,
      mainly in response to an increasing vapor pressure deficit (VPD) and gradual
      stomatal closure. The leaf water potential varied relatively little and did not
      influence gas exchange during the measurement period. Our results suggest that
      the same cause-effect relationships function at contrasting areas. However,
      leaves at the higher altitude had higher photosynthetic capacity, reflecting
      acclimation to higher light levels. Trees at both areas nevertheless achieved
      similar leaf assimilation rates since assimilation was down-regulated by stomatal
      closure due to the higher VPD at the higher altitude, while it became more light
      limited at the lower altitude. Gas exchange was thus limited by a high VPD or low
      light levels during the wet season, despite the ability of the species to
      acclimate to different conditions.

PMID- 21849594
TI  - Hydraulic function contributes to the variation in shoot morphology within the
      crown in Quercus crispula.
AB  - Hydraulic and light environments have variation within the crown in well-grown
      trees. Shoot morphology and shoot hydraulics were compared between the upper and
      lower crown or among branching patterns in well-grown Quercus crispula Blume.
      Shoots in the upper crown had longer and thicker axes and lower water potential
      than did shoots in the lower crown. Hydraulic conductance from the soil to the
      shoot did not differ between the upper crown and the lower crown. Shoots in the
      upper crown are exposed to hydraulic stress, and shoots in the lower crown are
      under shade stress. Shoot morphology and shoot hydraulic traits (i.e., higher
      Huber value and higher hydraulic conductivity) in the upper crown affected the
      hydraulic conductance of shoots. Shoots in the lower crown showed larger light
      receiving leaf area per leaf biomass investment, which is an adaptive morphology
      under shaded environments. Shoot morphology and shoot hydraulics were not
      correlated to branching pattern significantly, but shoots with higher branching
      intensity in the upper crown represented trends for higher hydraulic
      conductivity. These results reveal that shoot morphological and physiological
      characteristics in the upper crown reduce hydraulic stress, and those in the
      lower crown reduce shade stress. I conclude that vertical position within a crown
      affects both morphological and physiological acclimation for light acquisition
      and hydraulic conductance, and that hydraulic architecture is associated with
      crown architecture.

PMID- 21849595
TI  - Contributions of fat and protein to the incretin effect of a mixed meal.
AB  - BACKGROUND: The relative contributions of fat and protein to the incretin effect
      are still largely unknown. OBJECTIVE: This study assessed the incretin effects
      elicited by a mixed meal, and by its fat and protein components alone, with the
      use of a hyperglycemic clamp combined with oral nutrients. DESIGN: Eight healthy
      volunteers were studied over 6 h after ingestion of a sandwich containing 1)
      dried meat, butter, and white bread; 2) dried meat alone; 3) butter alone; or 4)
      no meal (fasting control). Meals were ingested during a hyperglycemic clamp, and
      the incretin effect was calculated as the increment in plasma insulin after food
      intake relative to the concentrations observed during the control study. RESULTS:
      A significant augmentation of postprandial insulin secretion, independent of
      plasma glycemia, occurred after ingestion of the mixed nutrients and the lipid
      component of the mixed meal (203 +/- 20.7% and 167.4 +/- 22.9% of control,
      respectively; both P < 0.05), whereas the protein component did not induce a
      significant incretin effect (129.0 +/- 7.9% of control; P = 0.6) CONCLUSIONS: Fat
      ingestion, in an amount typical of a standard meal, increases insulin secretion
      during physiologic hyperglycemia and thus contributes to the incretin effect. In
      contrast, ingestion of protein typical of normal meals does not contribute to the
      augmentation of postprandial insulin secretion. This trial was registered at
      clinicaltrials.gov as NCT00869453.

PMID- 21849596
TI  - Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on
      cognitive development of children at 6.5 y of age.
AB  - BACKGROUND: The influence of prenatal long-chain polyunsaturated fatty acids (LC
      PUFAs) and folate on neurologic development remains controversial. OBJECTIVE: The
      objective was to assess the long-term effects of n-3 (omega-3) LC-PUFA
      supplementation, 5-methyltetrahydrofolate (5-MTHF) supplementation, or both in
      pregnant women on cognitive development of offspring at 6.5 y of age. DESIGN:
      This was a follow-up study of the NUHEAL (Nutraceuticals for a Healthier Life)
      cohort. Healthy pregnant women in 3 European centers were randomly assigned to 4
      intervention groups. From the 20th week of pregnancy until delivery, they
      received a daily supplement of 500 mg docosahexaenoic acid (DHA) + 150 mg
      eicosapentaenoic acid [fish oil (FO)], 400 MUg 5-MTHF, or both or a placebo.
      Infants received formula containing 0.5% DHA and 0.4% arachidonic acid (AA) if
      they were born to mothers receiving FO supplements or were virtually free of DHA
      and AA until the age of 6 mo if they belonged to the groups that were not
      supplemented with FO. Fatty acids and folate concentrations were determined in
      maternal blood at weeks 20 and 30 of pregnancy, at delivery, and in cord blood.
      Cognitive function was assessed at 6.5 y of age with the Kaufman Assessment
      Battery for Children (K-ABC). RESULTS: We observed no significant differences in
      K-ABC scores between intervention groups. Higher DHA in maternal erythrocytes at
      delivery was associated with a Mental Processing Composite Score higher than the
      50th percentile in the offspring. CONCLUSION: We observed no significant effect
      of supplementation on the cognitive function of children, but maternal DHA status
      may be related to later cognitive function in children. This trial was registered
      at clinicaltrials.gov as NCT01180933.

PMID- 21849597
TI  - The guinea pig as a model for metabolic programming of adiposity.
AB  - BACKGROUND: The human infant accumulates body fat during intrauterine life. The
      guinea pig shares this characteristic and is born with similar adiposity; thus,
      it may be a relevant model to study obesity programming. OBJECTIVE: The objective
      of this study was to evaluate guinea pig adipose tissue (AT) development and the
      effect of a maternal high-fat diet on the offspring's body composition. DESIGN:
      In experiment 1, adipogenesis dynamics were evaluated at 3, 10, 21, and 136 d in
      epididymal and retroperitoneal AT with the use of (2)H(2)O labeling. In
      experiment 2, dams received a control or high-fat diet from mating to 21 d after
      delivery. The offspring received a high-fat diet from 22 to 105 d; adiposity was
      measured at 2, 21, 54, and 97 d. RESULTS: The fractional proliferation rate (FPR)
      of cells in epididymal AT was 25.2% of cells synthesized in 5 d at 3 d of age and
      decreased over time (P < 0.001). Age had no effect on retroperitoneal FPR (P =
      0.179). In both depots, the fractional synthesis rate (FSR) of palmitate
      decreased extensively from day 3 to day 10, increasing by day 21 and declining by
      day 136 (P < 0.001). The FSR of triglycerides decreased with age (P < 0.001). A
      maternal high-fat diet increased the offspring's adiposity at 2 d and 21 d (P <
      0.05) but had no effect on body composition later in life. CONCLUSIONS:
      Adipogenesis in the guinea pig is very active during early life and was altered
      by a maternal high-fat diet; thus, it is an adequate model for intrauterine fat
      deposition. However, there were no effects of maternal diet later in life.

PMID- 21849598
TI  - The Salmon in Pregnancy Study: study design, subject characteristics, maternal
      fish and marine n-3 fatty acid intake, and marine n-3 fatty acid status in
      maternal and umbilical cord blood.
AB  - BACKGROUND: Oily fish provides marine n-3 (omega-3) fatty acids that are
      considered to be important in the growth, development, and health of the fetus
      and newborn infant. OBJECTIVES: The objectives were to increase salmon
      consumption among pregnant women and to determine the effect on maternal and
      umbilical cord plasma marine n-3 fatty acid content. DESIGN: Women (n = 123) with
      low habitual consumption of oily fish were randomly assigned to continue their
      habitual diet or were provided with 2 portions of farmed salmon/wk to include in
      their diet from week 20 of pregnancy until delivery. RESULTS: Median weekly
      consumption frequency of study salmon in the salmon group was 1.94 portions, and
      total fish consumption frequency was 2.11 portions/wk in the salmon group and
      0.47 portions/wk in the control group (P < 0.001). Intakes of eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) from the diet, from seafood, and from
      oily fish were higher in the salmon group (all P < 0.001). Percentages of EPA and
      DHA in plasma phosphatidylcholine decreased during pregnancy in the control group
      (P for trend = 0.029 and 0.008, respectively), whereas they increased in the
      salmon group (P for trend for both < 0.001). EPA and DHA percentages were higher
      in maternal plasma phosphatidylcholine at weeks 34 and 38 of pregnancy and in
      umbilical cord plasma phosphatidylcholine in the salmon group (P < 0.001 for
      all). CONCLUSION: If pregnant women, who do not regularly eat oily fish, eat 2
      portions of salmon/wk, they will increase their intake of EPA and DHA, achieving
      the recommended minimum intake; and they will increase their and their fetus'
      status of EPA and DHA. This trial was registered at clinicaltrials.gov as
      NCT00801502.

PMID- 21849599
TI  - Developmental origins of health and disease: the views of first-time mothers in 5
      European countries on the importance of nutritional influences in the first year
      of life.
AB  - BACKGROUND: The programming concept suggests that poor early nutrition causes an
      array of medical problems later in life. Public health messages about the
      implications of programming may not be reaching parents and influencing infant
      feeding behaviors. OBJECTIVE: The views of new mothers were sought about the
      extent to which lifelong health is influenced by diet as an infant, rather than
      by genetic predispositions or lifestyles and behaviors. DESIGN: A questionnaire
      survey of first-time mothers was undertaken in 5 European countries. RESULTS: A
      convenience sample of 2071 mothers from England (438), Finland (426), Germany
      (414), Hungary (389), and Spain (404) self-completed the questionnaire. High
      proportions of mothers agreed that how an infant is fed affects his or her health
      over the first year (95.8%) and in subsequent years (88.5%), but the effect of
      infant feeding decisions on the development of long-term conditions was the least
      cited underlying reason. Diet as an infant was rated an extremely/very important
      influence on adult health by 64% of mothers, equivalent to environmental
      pollution (63%), but by fewer mothers than were diet and physical activity in
      childhood/adolescence (79%, 84%) and adulthood (81%, 83%), genetics/inheritance
      (70%), and exposure to cigarette smoke (81%). Inter- and intracountry differences
      were observed. CONCLUSIONS: Mothers in this study consider diet as an infant to
      be a less important influence on lifelong health than many lifestyle, behavioral,
      and environmental factors and genetics. Further dissemination of the implications
      of programming to consumers may be warranted.

PMID- 21849600
TI  - Salt sensitivity of blood pressure: developmental and sex-related effects.
AB  - Epidemiologic studies have shown convincingly that drastically reducing salt
      intake in the community is accompanied by blood pressure reductions that are
      comparable to those achieved by antihypertensive medication. Moreover, many
      subjects with hypertension are salt sensitive. This implies that, in these
      subjects, blood pressure is more responsive to changes in salt intake than in
      subjects with normal blood pressure. The presence of conventional risk factors
      associated with the metabolic syndrome correlates with salt sensitivity. However,
      women appear to be more salt sensitive than men. Sparse data indicate that the
      salt sensitivity of blood pressure is greater in subjects with low birth weight.
      Experimental studies in rats have also shown that hypertensive offspring of dams
      maintained on low-protein diets throughout or in late pregnancy are more salt
      sensitive. This is accompanied by increased expression of the thick ascending
      limb Na-K-2Cl symporter (NKCC2). Perinatal interventions aimed at persistently
      lowering blood pressure in genetically hypertensive rats have consistently proven
      to be very effective and are often accompanied by a wave of natriuresis
      exclusively at 4 wk of age. In sum, in addition to conventional metabolic risk
      factors for cardiovascular disease, low birth weight and possibly its sequels
      such as catch-up growth should be viewed as modifiable risk factors for salt
      sensitivity of blood pressure. Female sex may also be a nonmodifiable risk factor
      for salt sensitivity. Experimental data indicate that NKCC2 may well be an
      important determinant of salt sensitivity in acquired (developmental)
      hypertension.

PMID- 21849601
TI  - Long-term effects of hydrolyzed protein infant formulas on growth--extended
      follow-up to 10 y of age: results from the German Infant Nutritional Intervention
      (GINI) study.
AB  - BACKGROUND: Previous analysis in a prospective, population-based cohort reported
      reduced weight gain in children fed extensively hydrolyzed casein (eHF-C) formula
      during the first year of life but showed no effect on growth between 1 and 6 y of
      life. No studies have been conducted in children up to the age of 10 y.
      OBJECTIVE: The objective was to investigate potential differences in body mass
      index (BMI) over the first 10 y of life between infants fed within the
      intervention period of the first 16 wk of life with partially hydrolyzed whey
      (pHF-W), extensively hydrolyzed whey (eHF-W), eHF-C, or cow-milk formula (CMF)
      and infants exclusively breastfed (BF) within the intervention period. DESIGN:
      This was a prospective, randomized, double-blind trial in full-term neonates with
      atopic heredity in the German birth cohort German Infant Nutritional Intervention
      (GINI) followed through the first 10 y of life. Analyses of absolute and World
      Health Organization (WHO)-standardized BMI trajectories for 1840 infants [pHF-W
      (n = 253), eHF-W (n = 265), eHF-C (n = 250), CMF (n = 276), and BF (n = 796)]
      were conducted according to intention-to-treat principles. RESULTS: Except for
      the previously reported slower BMI gain in infants fed with eHF-C formula within
      the first year of life, no significant differences in absolute or WHO
      standardized BMI trajectories were shown between the pHF-W, eHF-W, eHF-C, CMF,
      and BF groups thereafter up to the age of 10 y. CONCLUSIONS: Extension of the
      follow-up period from 6 to 10 y for this randomized controlled trial showed no
      long-term consequences on BMI for the 4 infant formulas considered. These data
      need to be confirmed in future studies.

PMID- 21849602
TI  - Are early growth and nutrition related to bone health in adolescence? The
      Copenhagen Cohort Study of infant nutrition and growth.
AB  - BACKGROUND: It is generally accepted that peak bone mass affects later fracture
      risk in the elderly. The extent to which early nutrition and growth can program
      later bone health has been examined in only a few studies. In the Copenhagen
      Cohort Study we showed that breastfed infants had significantly higher serum (s)
      osteocalcin concentration than did formula-fed infants. OBJECTIVE: We
      investigated whether early nutrition and early growth are associated with later
      bone mass in adolescence. DESIGN: Participants were examined at birth; at ages 2,
      6, and 9 mo (n = 143); and at age 17 y (n = 109) with anthropometric and s
      osteocalcin measures and whole-body dual-energy X-ray absorptiometry (DXA)
      scanning (age 17 y only). Total body (T) and lumbar spine (LS) DXA values were
      used. RESULTS: The duration of exclusive breastfeeding was positively correlated
      with the sex-adjusted LS bone mineral content (BMC), LS bone area (BA), and LS
      bone mineral density (BMD) (all P < 0.03) and with size-adjusted LS-BMC (P =
      0.075) at 17 y of age. s-Osteocalcin at 6 mo was positively correlated with sex
      adjusted LS-BMC and LS-BMD (both P < 0.04) and with size-adjusted LS-BMC (P =
      0.047) at 17 y of age. Weight and length at 9 mo and increase in weight and
      length during the first 9 mo of life were positively correlated with sex-adjusted
      T-BMC and T-BA at age 17 y (all P < 0.04). CONCLUSIONS: Early body size and
      growth in infancy are related to bone mass in late adolescence. Furthermore, the
      duration of exclusive breastfeeding and the markers of bone turnover at 6 mo seem
      to be positively related to LS bone mass at age 17 y.

PMID- 21849603
TI  - Milk protein intake, the metabolic-endocrine response, and growth in infancy:
      data from a randomized clinical trial.
AB  - BACKGROUND: Protein intake in early infancy has been suggested to be an important
      risk factor for later obesity, but information on potential mechanisms is very
      limited. OBJECTIVE: This study examined the influence of protein intake in
      infancy on serum amino acids, insulin, and the insulin-like growth factor I (IGF
      I) axis and its possible relation to growth in the first 2 y of life. DESIGN: In
      a multicenter European study, 1138 healthy, formula-fed infants were randomly
      assigned to receive cow-milk-based infant and follow-on formulas with lower
      protein (LP; 1.77 and 2.2 g protein/100 kcal) or higher protein (HP; 2.9 and 4.4
      g protein/100 kcal) contents for the first year. Biochemical variables were
      measured at age 6 mo in 339 infants receiving LP formula and 333 infants
      receiving HP formula and in 237 breastfed infants. RESULTS: Essential amino
      acids, especially branched-chain amino acids, IGF-I, and urinary C
      peptide:creatinine ratio, were significantly (P < 0.001) higher in the HP group
      than in the LP group, whereas IGF-binding protein (IGF-BP) 2 was lower and IGF
      BP3 did not differ significantly. The median IGF-I total serum concentration was
      48.4 ng/mL (25th, 75th percentile: 27.2, 81.8 ng/mL) in the HP group and 34.7
      ng/mL (17.7, 57.5 ng/mL) in the LP group; the urine C-peptide:creatinine ratios
      were 140.6 ng/mg (80.0, 203.8 ng/mg) and 107.3 ng/mg (65.2, 194.7 ng/mg),
      respectively. Most essential amino acids, IGF-I, C-peptide, and urea increased
      significantly in both the LP and HP groups compared with the breastfed group.
      Total IGF-I was significantly associated with growth until 6 mo but not
      thereafter. CONCLUSIONS: HP intake stimulates the IGF-I axis and insulin release
      in infancy. IGF-I enhances growth during the first 6 mo of life. This trial was
      registered at clinicaltrials.gov as NCT00338689.

PMID- 21849604
TI  - Suppression of smooth pursuit eye movements induced by electrical stimulation of
      the monkey frontal eye field.
AB  - This study was performed to characterize the properties of the suppression of
      smooth pursuit eye movement induced by electrical stimulation of the frontal eye
      field (FEF) in trained monkeys. At the stimulation sites tested, we first
      determined the threshold for generating electrically evoked saccades (Esacs). We
      then examined the suppressive effects of stimulation on smooth pursuit at
      intensities that were below the threshold for eliciting Esacs. We observed that
      FEF stimulation induced a clear deceleration of pursuit at pursuit initiation and
      also during the maintenance of pursuit at subthreshold intensities. The
      suppression of pursuit occurred even in the absence of catch-up saccades during
      pursuit, indicating that suppression influenced pursuit per se. We mapped the FEF
      area that was associated with the suppressive effect of stimulation on pursuit.
      In a wide area in the FEF, suppressive effects were observed for ipsiversive, but
      not contraversive, pursuit. In contrast, we observed the bilateral suppression of
      both ipsiversive and contraversive pursuit in a localized area in the FEF. This
      area coincided with the area in which we have previously shown that stimulation
      suppressed the generation of saccades in bilateral directions and also where
      fixation neurons that discharged during fixation were concentrated. On the basis
      of these results, we compared the FEF suppression of pursuit with that of
      saccades with regard to several physiological properties and then discussed the
      role of the FEF in the suppression of both pursuit and saccades, and particularly
      in the maintenance of visual fixation.

PMID- 21849606
TI  - Distributed representation of social odors indicates parallel processing in the
      antennal lobe of ants.
AB  - In colonies of eusocial Hymenoptera cooperation is organized through social
      odors, and particularly ants rely on a sophisticated odor communication system.
      Neuronal information about odors is represented in spatial activity patterns in
      the primary olfactory neuropile of the insect brain, the antennal lobe (AL),
      which is analog to the vertebrate olfactory bulb. The olfactory system is
      characterized by neuroanatomical compartmentalization, yet the functional
      significance of this organization is unclear. Using two-photon calcium imaging,
      we investigated the neuronal representation of multicomponent colony odors, which
      the ants assess to discriminate friends (nestmates) from foes (nonnestmates). In
      the carpenter ant Camponotus floridanus, colony odors elicited spatial activity
      patterns distributed across different AL compartments. Activity patterns in
      response to nestmate and nonnestmate colony odors were overlapping. This was
      expected since both consist of the same components at differing ratios. Colony
      odors change over time and the nervous system has to constantly adjust for this
      (template reformation). Measured activity patterns were variable, and variability
      was higher in response to repeated nestmate than to repeated nonnestmate colony
      odor stimulation. Variable activity patterns may indicate neuronal plasticity
      within the olfactory system, which is necessary for template reformation. Our
      results indicate that information about colony odors is processed in parallel in
      different neuroanatomical compartments, using the computational power of the
      whole AL network. Parallel processing might be advantageous, allowing reliable
      discrimination of highly complex social odors.

PMID- 21849605
TI  - Behavioral training restores temporal processing in auditory cortex of long-deaf
      cats.
AB  - Temporal auditory processing is poor in prelingually hearing-impaired patients
      fitted with cochlear prostheses as adults. In an animal model of prelingual long
      term deafness, we investigated the effects of behavioral training on temporal
      processing in the adult primary auditory cortex (AI). Neuronal responses to pulse
      trains of increasing frequencies were recorded in three groups of neonatally
      deafened cats that received a cochlear prosthesis after >3 yr of deafness: 1)
      acutely implanted animals that received no electric stimulation before study, 2)
      animals that received chronic-passive stimulation for several weeks to months
      before study, and 3) animals that received chronic-passive stimulation and
      additional behavioral training (signal detection). A fourth group of normal adult
      cats that was deafened acutely and implanted served as controls. The neuronal
      temporal response parameters of interest included the stimulus rate that evoked
      the maximum number of phase-locked spikes [best repetition rate (BRR)], the
      stimulus rate that produced 50% of the spike count at BRR (cutoff rate), the peak
      response latency, and the first spike latency and timing-jitter. All long-deaf
      animals demonstrated a severe reduction in spiral ganglion cell density (mean,
      <6% of normal). Long-term deafness resulted in a significantly reduced temporal
      following capacity and spike-timing precision of cortical neurons in all
      parameters tested. Neurons in deaf animals that received only chronic-passive
      stimulation showed a gain in BRR but otherwise were similar to deaf cats that
      received no stimulation. In contrast, training with behaviorally relevant
      stimulation significantly enhanced all temporal processing parameters to normal
      levels with the exception of minimum latencies. These results demonstrate the
      high efficacy of learning-based remodeling of fundamental timing properties in
      cortical processing even in the adult, long-deaf auditory system, suggesting
      rehabilitative strategies for patients with long-term hearing loss.

PMID- 21849607
TI  - Rebound excitation triggered by synaptic inhibition in cerebellar nuclear neurons
      is suppressed by selective T-type calcium channel block.
AB  - Following hyperpolarizing inputs, many neurons respond with an increase in firing
      rate, a phenomenon known as rebound excitation. Rebound excitation has been
      proposed as a mechanism to encode and process inhibitory signals and transfer
      them to target structures. Activation of low-voltage-activated T-type calcium
      channels and the ensuing low-threshold calcium spikes is one of the mechanisms
      proposed to support rebound excitation. However, there is still not enough
      evidence that the hyperpolarization provided by inhibitory inputs, particularly
      those dependent on chloride ions, is adequate to deinactivate a sufficient number
      of T-type calcium channels to drive rebound excitation on return to baseline.
      Here, this issue was investigated in the deep cerebellar nuclear neurons (DCNs),
      which receive the output of the cerebellar cortex conveyed exclusively by the
      inhibitory Purkinje cells and are also known to display rebound excitation. Using
      cerebellar slices and whole cell recordings of large DCNs, we show that a novel
      piperidine-based compound that selectively antagonizes T-type calcium channel
      activity, 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydropyran-4-ylmethyl)-4-fluoro
      piperidin-4-ylmethyl]-benzamide (TTA-P2), suppressed rebound excitation elicited
      by current injection as well as by synaptic inhibition, whereas other
      electrophysiological properties of large DCNs were unaltered. Furthermore, TTA-P2
      suppressed transient high-frequency rebounds found in DCNs with low-threshold
      spikes as well as the slow rebounds present in DCNs without low-threshold spikes.
      These findings demonstrate that chloride-dependent synaptic inhibition
      effectively triggers T-type calcium channel-mediated rebounds and that the latter
      channels may support slow rebound excitation in neurons without low-threshold
      spikes.

PMID- 21849608
TI  - Selectivity for the rate of frequency-modulated sweeps in the mouse auditory
      cortex.
AB  - Frequency-modulated (FM) sweeps are common components of vocalizations, including
      human speech. Both sweep direction and rate influence discrimination of
      vocalizations. Across species, relatively less is known about FM rate selectivity
      compared with direction selectivity. In this study, FM rate selectivity was
      studied in the auditory cortex of anesthetized 1- to 3-mo-old C57bl/6 mice.
      Neurons were classified as fast pass, band pass, slow pass, or all pass depending
      on their selectivity for rates between 0.08 and 20 kHz/ms. Multiunit recordings
      were used to map FM rate selectivity at depths between 250 and 450 MUm across
      both primary auditory cortex (A1) and the anterior auditory field (AAF). In terms
      of functional organization of rate selectivity, three patterns were found. First,
      in both A1 and AAF, neurons clustered according to rate selectivity. Second, most
      (~60%) AAF neurons were either fast-pass or band-pass selective. Most A1 neurons
      (~72%) were slow-pass selective. This distribution supports the hypothesis that
      AAF is specialized for faster temporal processing than A1. Single-unit recordings
      (n = 223) from A1 and AAF show that the mouse auditory cortex is best poised to
      detect and discriminate a narrow range of sweep rates between 0.5 and 3 kHz/ms.
      Third, based on recordings obtained at different depths, neurons in the
      infragranular layers were less rate selective than neurons in the granular
      layers, suggesting FM processing undergoes changes within the cortical column. On
      average, there was very little direction selectivity in the mouse auditory
      cortex. There was also no correlation between characteristic frequency and
      direction selectivity. The narrow range of rate selectivity in the mouse cortex
      indicates that FM rate processing is a useful physiological marker for studying
      contributions of genetic and environmental factors in auditory system
      development, aging, and disease.

PMID- 21849609
TI  - Hydrogen peroxide differentially affects activity in the pre-Botzinger complex
      and hippocampus.
AB  - Reactive oxygen species (ROS) modulate neuronal excitability. In the present
      study we examined the effects of hydrogen peroxide (H(2)O(2)), a well established
      ROS, on neuronal activity from two neonatal mouse brain regions, i.e., the pre
      Botzinger complex (preBotC) within the ventral respiratory column (VRC) and the
      CA1 area of the hippocampus. In the preBotC, 2.2 mM H(2)O(2) evoked a transient
      depression followed by augmentation of neuronal activity. The iron chelator
      deferoxamine (500 MUM) did not prevent H(2)O(2)-mediated neuronal augmentation
      but prevented the initial depression. Combined application of Fe(2+) and H(2)O(2)
      only caused depression of the preBotC rhythm. In contrast, H(2)O(2) suppressed
      neuronal activity in the CA1 region, and this effect was accentuated by
      coapplication of Fe(2+) and H(2)O(2), suggesting that hydroxyl radical generated
      by Fenton reaction mediates the effects of H(2)O(2) on CA1 neuronal activity.
      Malondialdehyde (MDA) levels were monitored as an index of lipid peroxidation in
      H(2)O(2)-treated preBotC and CA1 areas. MDA levels were unaltered in H(2)O(2)
      treated preBotC, whereas MDA levels were markedly elevated in the CA1 region.
      These findings suggest that 1) exogenous administration of H(2)O(2) exerts
      differential effects on neuronal activities of preBotC versus CA1 neuronal
      populations and 2) H(2)O(2) is a potent modulator of respiratory rhythmogenesis
      from the preBotC without affecting global oxidative status.

PMID- 21849610
TI  - Reward skewness coding in the insula independent of probability and loss.
AB  - Rewards in the natural environment are rarely predicted with complete certainty.
      Uncertainty relating to future rewards has typically been defined as the variance
      of the potential outcomes. However, the asymmetry of predicted reward
      distributions, known as skewness, constitutes a distinct but neuroscientifically
      underexplored risk term that may also have an impact on preference. By changing
      only reward magnitudes, we study skewness processing in equiprobable ternary
      lotteries involving only gains and constant probabilities, thus excluding
      probability distortion or loss aversion as mechanisms for skewness preference
      formation. We show that individual preferences are sensitive to not only the mean
      and variance but also to the skewness of predicted reward distributions. Using
      neuroimaging, we show that the insula, a structure previously implicated in the
      processing of reward-related uncertainty, responds to the skewness of predicted
      reward distributions. Some insula responses increased in a monotonic fashion with
      skewness (irrespective of individual skewness preferences), whereas others were
      similarly elevated to both negative and positive as opposed to no reward skew.
      These data support the notion that the asymmetry of reward distributions is
      processed in the brain and, taken together with replicated findings of mean
      coding in the striatum and variance coding in the cingulate, suggest that the
      brain codes distinct aspects of reward distributions in a distributed fashion.

PMID- 21849611
TI  - Spatial tuning to sound-source azimuth in the inferior colliculus of
      unanesthetized rabbit.
AB  - Despite decades of research devoted to the study of inferior colliculus (IC)
      neurons' tuning to sound-source azimuth, there remain many unanswered questions
      because no previous study has examined azimuth tuning over a full range of 360
      degrees  azimuths at a wide range of stimulus levels in an unanesthetized
      preparation. Furthermore, a comparison of azimuth tuning to binaural and
      contralateral ear stimulation over ranges of full azimuths and widely varying
      stimulus levels has not previously been reported. To fill this void, we have
      conducted a study of azimuth tuning in the IC of the unanesthetized rabbit over a
      300 degrees  range of azimuths at stimulus levels of 10-50 dB above neural
      threshold to both binaural and contralateral ear stimulation using virtual
      auditory space stimuli. This study provides systematic evidence for neural coding
      of azimuth. We found the following: 1) level-tolerant azimuth tuning was observed
      in the top 35% regarding vector strength and in the top 15% regarding vector
      angle of IC neurons; 2) preserved azimuth tuning to binaural stimulation at high
      stimulus levels was created as a consequence of binaural facilitation in the
      contralateral sound field and binaural suppression in the ipsilateral sound
      field; 3) the direction of azimuth tuning to binaural stimulation was primarily
      in the contralateral sound field, and its center shifted laterally toward -90
      degrees  with increasing stimulus level; 4) at 10 dB, azimuth tuning to binaural
      and contralateral stimulation was similar, indicating that it was mediated by
      monaural mechanisms; and 5) at higher stimulus levels, azimuth tuning to
      contralateral ear stimulation was severely degraded. These findings form a
      foundation for understanding neural mechanisms of localizing sound-source
      azimuth.

PMID- 21849612
TI  - Neural correlates of evidence accumulation in a perceptual decision task.
AB  - Sequential sampling models provide a useful framework for understanding human
      decision making. A key component of these models is an evidence accumulation
      process in which information is accrued over time to a threshold, at which point
      a choice is made. Previous neurophysiological studies on perceptual decision
      making have suggested accumulation occurs only in sensorimotor areas involved in
      making the action for the choice. Here we investigated the neural correlates of
      evidence accumulation in the human brain using functional magnetic resonance
      imaging (fMRI) while manipulating the quality of sensory evidence, the response
      modality, and the foreknowledge of the response modality. We trained subjects to
      perform a random dot motion direction discrimination task by either moving their
      eyes or pressing buttons to make their responses. In addition, they were cued
      about the response modality either in advance of the stimulus or after a delay.
      We isolated fMRI responses for perceptual decisions in both independently defined
      sensorimotor areas and task-defined nonsensorimotor areas. We found neural
      signatures of evidence accumulation, a higher fMRI response on low coherence
      trials than high coherence trials, primarily in saccade-related sensorimotor
      areas (frontal eye field and intraparietal sulcus) and nonsensorimotor areas in
      anterior insula and inferior frontal sulcus. Critically, such neural signatures
      did not depend on response modality or foreknowledge. These results help
      establish human brain areas involved in evidence accumulation and suggest that
      the neural mechanism for evidence accumulation is not specific to effectors.
      Instead, the neural system might accumulate evidence for particular stimulus
      features relevant to a perceptual task.

PMID- 21849613
TI  - Patterns of hypermetria and terminal cocontraction during point-to-point
      movements demonstrate independent action of trajectory and postural controllers.
AB  - We examined elbow muscle activities and movement kinematics to determine how
      subjects combine elementary control actions in performing movements with one and
      two trajectory segments. In reaching, subjects made a rapid elbow flexion to a
      visual target before stabilizing the limb with either a low or a higher level of
      elbow flexor/extensor coactivity (CoA), which was cued by target diameter. Cursor
      diameter provided real-time biofeedback of actual muscle CoA. In reversing, the
      limb was to reverse direction within the target and return to the origin with
      minimal CoA. We previously reported that subjects overshoot the goal when
      attempting a reversal after first having learned to reach accurately to the same
      target. Here we test the hypothesis that this hypermetria results because
      reversals co-opt the initial feedforward control action from the preceding
      trained reach, thereby failing to account for task-dependent changes in limb
      impedance induced by differences in flexor/extensor coactivity as the target is
      acquired (higher in reaching than reversing). Instructed increases in elbow CoA
      began mid-reach, thus increasing elbow impedance and reducing transient
      oscillations present in low CoA movments. Flexor EMG alone increased at movement
      onset. Test reversals incorporated the initial agonist activity of previous
      reaches but not the increased coactivity at the target, thus leading to
      overshoot. Moreover, we observed elevated coactivity in reversals upon returning
      to the origin even though coactivity in reaching was centered at the goal target.
      These findings refute the idea that the brain necessarily invokes distinct
      unitary control actions for reaches and reversals made to the same target.
      Instead, reaches and reversals share a common control action that initiates
      trajectories toward their target and another later control action that terminates
      movement and stabilizes the limb about its final resting posture, which differs
      in the two tasks.

PMID- 21849615
TI  - Neural response dynamics of spiking and local field potential activity depend on
      CRT monitor refresh rate in the tree shrew primary visual cortex.
AB  - Entrainment of neural activity to luminance impulses during the refresh of
      cathode ray tube monitor displays has been observed in the primary visual cortex
      (V1) of humans and macaque monkeys. This entrainment is of interest because it
      tends to temporally align and thus synchronize neural responses at the
      millisecond timescale. Here we show that, in tree shrew V1, both spiking and
      local field potential activity are also entrained at cathode ray tube refresh
      rates of 120, 90, and 60 Hz, with weakest but still significant entrainment even
      at 120 Hz, and strongest entrainment occurring in cortical input layer IV. For
      both luminance increments ("white" stimuli) and decrements ("black" stimuli),
      refresh rate had a strong impact on the temporal dynamics of the neural response
      for subsequent luminance impulses. Whereas there was rapid, strong attenuation of
      spikes and local field potential to prolonged visual stimuli composed of
      luminance impulses presented at 120 Hz, attenuation was nearly absent at 60-Hz
      refresh rate. In addition, neural onset latencies were shortest at 120 Hz and
      substantially increased, by ~15 ms, at 60 Hz. In terms of neural response
      amplitude, black responses dominated white responses at all three refresh rates.
      However, black/white differences were much larger at 60 Hz than at higher refresh
      rates, suggesting a mechanism that is sensitive to stimulus timing. Taken
      together, our findings reveal many similarities between V1 of macaque and tree
      shrew, while underscoring a greater temporal sensitivity of the tree shrew visual
      system.

PMID- 21849614
TI  - Strain differences in the neural, behavioral, and molecular correlates of sweet
      and salty taste in naive, ethanol- and sucrose-exposed P and NP rats.
AB  - Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring
      (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of
      ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and
      salty stimuli; and gene expression in the anterior tongue of T1R3 and
      TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet
      stimuli, and T1R3 expression were greater in naive P rats than NP rats. The
      enhancement of the CT response to 0.5 M sucrose in the presence of varying
      ethanol concentrations (0.5-40%) in naive P rats was higher and shifted to lower
      ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5%
      ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated
      bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t
      agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the
      response at low concentrations and inhibiting it at high concentrations. The
      concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated
      with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil
      CT response induced a decrease in NaCl intake and preference in P rats. In naive
      P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic
      TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to
      lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression
      increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice
      paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t
      expression and neural and behavioral responses to sweet and salty stimuli and to
      chronic sucrose and ethanol exposure.

PMID- 21849616
TI  - Stereotypical spatiotemporal activity patterns during slow-wave activity in the
      neocortex.
AB  - Alternating epochs of activity and silence are a characteristic feature of
      neocortical networks during certain sleep cycles and deep states of anesthesia.
      The mechanism and functional role of these slow oscillations (<1 Hz) have not yet
      been fully characterized. Experimental and theoretical studies show that slow
      wave oscillations can be generated autonomously by neocortical tissue but become
      more regular through a thalamo-cortical feedback loop. Evidence for a functional
      role of slow-wave activity comes from EEG recordings in humans during sleep,
      which show that activity travels as stereotypical waves over the entire brain,
      thought to play a role in memory consolidation. We used an animal model to
      investigate activity wave propagation on a smaller scale, namely within the rat
      somatosensory cortex. Signals from multiple extracellular microelectrodes in
      combination with one intracellular recording in the anesthetized animal in vivo
      were utilized to monitor the spreading of activity. We found that activity
      propagation in most animals showed a clear preferred direction, suggesting that
      it often originated from a similar location in the cortex. In addition, the
      breakdown of active states followed a similar pattern with slightly weaker
      direction preference but a clear correlation to the direction of activity
      spreading, supporting the notion of a wave-like phenomenon similar to that
      observed after strong sensory stimulation in sensory areas. Taken together, our
      findings support the idea that activity waves during slow-wave sleep do not occur
      spontaneously at random locations within the network, as was suggested
      previously, but follow preferred synaptic pathways on a small spatial scale.

PMID- 21849617
TI  - Impedance control is selectively tuned to multiple directions of movement.
AB  - Humans are able to learn tool-handling tasks, such as carving, demonstrating
      their competency to make movements in unstable environments with varied
      directions. When faced with a single direction of instability, humans learn to
      selectively co-contract their arm muscles tuning the mechanical stiffness of the
      limb end point to stabilize movements. This study examines, for the first time,
      subjects simultaneously adapting to two distinct directions of instability, a
      situation that may typically occur when using tools. Subjects learned to perform
      reaching movements in two directions, each of which had lateral instability
      requiring control of impedance. The subjects were able to adapt to these unstable
      interactions and switch between movements in the two directions; they did so by
      learning to selectively control the end-point stiffness counteracting the
      environmental instability without superfluous stiffness in other directions. This
      finding demonstrates that the central nervous system can simultaneously tune the
      mechanical impedance of the limbs to multiple movements by learning movement
      specific solutions. Furthermore, it suggests that the impedance controller learns
      as a function of the state of the arm rather than a general strategy.

PMID- 21849618
TI  - Task goals influence online corrections and adaptation of reaching movements.
AB  - Everyday movements often have multiple solutions. Many of these solutions arise
      from biomechanical redundancies. Often, however, the goal does not require a
      unique movement. To examine how people exploit task-related redundancy, we
      observed as participants produced three-dimensional (3-D) reaching movements,
      moving to one of two rectangular targets that were diagonally oriented in the
      frontal (x, y) plane. On most trials, the movement was perturbed by a vertical,
      velocity-dependent force. Since participants were free to move in 3-D space,
      online corrections could involve movement along the perturbed, vertical
      dimension, as well as the nonperturbed, horizontal dimension. If the motor system
      exploits task redundancies, then corrections along the horizontal dimension
      should depend on the orientation of the target. Consistent with this prediction,
      participants modified both the horizontal and vertical coordinates of the
      trajectory over the course of learning, and the horizontal component was
      sensitive to the orientation of the target. Furthermore, participants produced
      online corrections with a horizontal component that brought the hand closer to
      the target. These results suggest that we not only correct for mismatches between
      expected and experienced forces but also exploit task-specific redundancies to
      efficiently improve performance.

PMID- 21849619
TI  - Cis-regulatory code of stress-responsive transcription in Arabidopsis thaliana.
AB  - Environmental stress leads to dramatic transcriptional reprogramming, which is
      central to plant survival. Although substantial knowledge has accumulated on how
      a few plant cis-regulatory elements (CREs) function in stress regulation, many
      more CREs remain to be discovered. In addition, the plant stress cis-regulatory
      code, i.e., how CREs work independently and/or in concert to specify stress
      responsive transcription, is mostly unknown. On the basis of gene expression
      patterns under multiple stresses, we identified a large number of putative CREs
      (pCREs) in Arabidopsis thaliana with characteristics of authentic cis-elements.
      Surprisingly, biotic and abiotic responses are mostly mediated by two distinct
      pCRE superfamilies. In addition, we uncovered cis-regulatory codes specifying how
      pCRE presence and absence, combinatorial relationships, location, and copy number
      can be used to predict stress-responsive expression. Expression prediction models
      based on pCRE combinations perform significantly better than those based on
      simply pCRE presence and absence, location, and copy number. Furthermore, instead
      of a few master combinatorial rules for each stress condition, many rules were
      discovered, and each appears to control only a small subset of stress-responsive
      genes. Given there are very few documented interactions between plant CREs, the
      combinatorial rules we have uncovered significantly contribute to a better
      understanding of the cis-regulatory logic underlying plant stress response and
      provide prioritized targets for experimentation.

PMID- 21849620
TI  - Isoleucine 309 acts as a C4 catalytic switch that increases ribulose-1,5
      bisphosphate carboxylase/oxygenase (rubisco) carboxylation rate in Flaveria.
AB  - Improving global yields of important agricultural crops is a complex challenge.
      Enhancing yield and resource use by engineering improvements to photosynthetic
      carbon assimilation is one potential solution. During the last 40 million years
      C(4) photosynthesis has evolved multiple times, enabling plants to evade the
      catalytic inadequacies of the CO(2)-fixing enzyme, ribulose-1,5-bisphosphate
      carboxylase/oxygenase (rubisco). Compared with their C(3) ancestors, C(4) plants
      combine a faster rubisco with a biochemical CO(2)-concentrating mechanism,
      enabling more efficient use of water and nitrogen and enhanced yield. Here we
      show the versatility of plastome manipulation in tobacco for identifying
      sequences in C(4)-rubisco that can be transplanted into C(3)-rubisco to improve
      carboxylation rate (V(C)). Using transplastomic tobacco lines expressing native
      and mutated rubisco large subunits (L-subunits) from Flaveria pringlei (C(3)),
      Flaveria floridana (C(3)-C(4)), and Flaveria bidentis (C(4)), we reveal that Met
      309-Ile substitutions in the L-subunit act as a catalytic switch between C(4)
      ((309)Ile; faster V(C), lower CO(2) affinity) and C(3) ((309)Met; slower V(C),
      higher CO(2) affinity) catalysis. Application of this transplastomic system
      permits further identification of other structural solutions selected by nature
      that can increase rubisco V(C) in C(3) crops. Coengineering a catalytically
      faster C(3) rubisco and a CO(2)-concentrating mechanism within C(3) crop species
      could enhance their efficiency in resource use and yield.

PMID- 21849621
TI  - Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia
      telangiectasia mutated (ATM) protein.
AB  - Stability and repair of DNA is of principal importance in cell survival. Heme
      oxygenase-1 (HO-1; Hmox1) is critical in maintaining cellular homeostasis, in
      large part through its ability to generate CO, but neither molecule has been
      studied in the setting of DNA damage. Naive Hmox1(-/-) mice exhibit excessive
      tissue levels of gamma-histone H2A, whereas administration of genotoxic stressors
      or irradiation in HO-1-deficient cells resulted in loss of ataxia-telangiectasia
      mutated/ataxia telangiectasia and Rad3-related protein and breast cancer 1, early
      onset induction with dysfunctional gamma-H2AX foci and marked elevations in DNA
      damage. HO-1 induction or exposure to CO induced homologous recombination
      mediated DNA repair through ataxia-telangiectasia mutated/ataxia telangiectasia
      and Rad3-related protein. In vivo, exposure of mice to CO followed by genotoxin
      (Adriamycin) or radiation-induced injury led to diminished tissue DNA damage and
      improved survival. We characterize a joint role for HO-1 and the gasotransmitter
      CO for appropriate DNA repair and provide a mechanism for their potent
      cytoprotective effects in various pathologies.

PMID- 21849622
TI  - Site-specific and redox-controlled S-nitrosation of thioredoxin.
AB  - Protein S-nitrosation on cysteine residues has emerged as an important
      posttranslational modification in mammalian cells. Previous studies have
      suggested a primary role for thioredoxin (Trx) in controlling protein S
      nitrosation reactions. Human Trx contains five conserved Cys, including two redox
      active catalytic Cys (Cys32 and Cys35) and three non-active-site Cys (Cys62,
      Cys69, and Cys73), all of which have been reported as targets of S-nitrosation.
      Prior reports have studied thermodynamic end points of nitrosation reactions;
      however, the kinetics of Trx nitrosation has not previously been investigated.
      Using the transnitrosation agent, S-nitrosoglutathione, a kinetic analysis of the
      selectivity and redox dependence of Trx nitrosation at physiologically relevant
      concentrations and times was performed, utilizing a mass spectrometry-based
      method for the direct analysis of the nitrosated Trx. Reduced Trx (rTrx) was
      nitrosated 2.7-times faster than oxidized Trx (oTrx), and rTrx was nitrosated
      selectively on Cys62, whereas oTrx was nitrosated only on Cys73. These sites of
      nitrosation were confirmed at the peptide level using a novel modification of the
      biotin-switch technique called the reductive switch. These results suggest
      separate signaling pathways for Trx-SNO under different cellular redox states.

PMID- 21849623
TI  - Immunochemical detection of cytochrome P450 enzymes in liver microsomes of 27
      cynomolgus monkeys.
AB  - The cynomolgus monkey is widely used as a primate model in preclinical studies
      because of its evolutionary closeness to humans. Despite their importance in drug
      metabolism, the content of each cytochrome P450 (P450) enzyme has not been
      systematically determined in cynomolgus monkey livers. In this study, liver
      microsomes of 27 cynomolgus monkeys were analyzed by immunoblotting using
      selective P450 antibodies. The specificity of each antibody was confirmed by
      analyzing the cross-reactivity against 19 CYP1-3 subfamily enzymes using
      recombinant proteins. CYP2A, CYP2B6, CYP2C9/19, CYP2C76, CYP2D, CYP2E, CYP3A4,
      and CYP3A5 were detected in all 27 animals. In contrast, CYP1A, CYP1D, and CYP2J
      were below detectable levels in all liver samples. The average content of each
      P450 showed that among the P450s analyzed CYP3A (3A4 and 3A5) was the most
      abundant (40% of total immunoquantified P450), followed by CYP2A (25%), CYP2C
      (14%), CYP2B6 (13%), CYP2E1 (11%), and CYP2D (3%). No apparent sex differences
      were found for any P450. Interanimal variations ranged from 2.6-fold (CYP3A) to
      11-fold (CYP2C9/19), and most P450s (CYP2A, CYP2D, CYP2E, CYP3A4, and CYP3A5)
      varied 3- to 4-fold. To examine the correlations of P450 content with enzyme
      activities, metabolic assays were performed in 27 cynomolgus monkey livers using
      7-ethoxyresorufin, coumarin, pentoxyresorufin, flurbiprofen, bufuralol,
      dextromethorphan, and midazolam. CYP2D and CYP3A4 contents were significantly
      correlated with typical reactions of human CYP2D (bufuralol 1'-hydroxylation and
      dextromethorphan O-deethylation) and CYP3A (midazolam 1'-hydroxylation and 4
      hydroxylation). The results presented in this study provide useful information
      for drug metabolism studies using cynomolgus monkeys.

PMID- 21849624
TI  - Drug discontinuation effects are part of the pharmacology of a drug.
AB  - Most reviews of drug withdrawal effects focus on drugs of potential abuse such as
      opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in
      medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation
      of a number of cardiovascular drugs can increase risk of cardiovascular events
      above that of people not taking these drugs. These include beta-adrenergic
      receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and
      heparin. Rebound hypertension occurs after abrupt cessation of many
      antihypertensive drugs. The possibility of discontinuation syndromes has usually
      been neglected until adverse clinical events force them to be noticed. Attention
      to the possibility of drug discontinuation effects is an important part of drug
      safety evaluation.

PMID- 21849625
TI  - Development of a high-affinity inhibitor of the prostaglandin transporter.
AB  - Prostaglandin E(2) (PGE(2)) triggers a vast array of biological signals and
      physiological events. The prostaglandin transporter (PGT) controls PGE(2) influx
      and is rate-limiting for PGE(2) metabolism and signaling termination. PGT global
      knockout mice die on postnatal day 1 from patent ductus arteriosus. A high
      affinity PGT inhibitor would thus be a powerful tool for studying PGT function in
      adult animals. Moreover, such an inhibitor could be potentially developed into a
      therapeutic drug targeting PGT. Based on structure-activity relationship studies
      that built on recently identified inhibitors of PGT, we obtained N-(2-(2-(2
      azidoethoxy)ethoxy)ethyl)-4-((4-((2-(2-(2-benzamidoethoxy)ethoxy)ethyl)amino)-6
      ((4-hydroxyphenyl)amino)-1,3,5-triazin-2-yl)amino)benzamide (T26A), a competitive
      inhibitor of PGT, with a K(i) of 378 nM. T26A seems to be highly selective for
      PGT, because it neither interacts with a PGT homolog in the organic anion
      transporter family nor affects PGE(2) synthesis. In Madin-Darby canine kidney
      cells stably transfected with PGT, T26A blocked PGE(2) metabolism, resulting in
      retention of PGE(2) in the extracellular compartment and the negligible
      appearance of PGE(2) metabolites in the intracellular compartment. Compared with
      vehicle, T26A injected intravenously into rats effectively doubled the amount of
      endogenous PGE(2) in the circulation and reduced the level of circulating
      endogenous PGE(2) metabolites to 50%. Intravenous T26A was also able to slow the
      metabolism of exogenously injected PGE(2). These results confirm that PGT
      directly regulates PGE(2) metabolism and demonstrate that a high-affinity
      inhibitor of PGT can effectively prevent PGE(2) metabolism and prolong the half
      life of circulating PGE(2).

PMID- 21849626
TI  - The translational efficacy of a nonsteroidal progesterone receptor antagonist, 4
      [3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6
      dimethylbenzonitrile (PF-02413873), on endometrial growth in macaque and human.
AB  - There is considerable ongoing investment in the research and development of
      selective progesterone receptor (PR) modulators for the treatment of
      gynecological conditions such as endometriosis. Here, we provide the first report
      on the clinical evaluation of a nonsteroidal progesterone receptor antagonist 4
      [3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6
      dimethylbenzonitrile (PF-02413873) in healthy female subjects. In in vitro
      assays, PF-02413873 behaved as a selective and fully competitive PR antagonist,
      blocking progesterone binding and PR nuclear translocation. The pharmacological
      mode of action of PF-02413873 seems to differ from the founding member of the
      class of steroidal PR antagonists, 11beta-4-dimethylaminophenyl-17beta-hydroxy
      17alpha-propinyl-4,9-estradiene-3-one (RU-486; mifepristone). Exposure-effect
      data from studies in the cynomolgus macaque, however, demonstrated that PF
      02413873 reduced endometrial functionalis thickness to a comparable degree to RU
      486 and this effect was accompanied by a decrease in proliferation rate (as
      measured by bromodeoxyuridine incorporation) for both RU-486 and high-dose PF
      02413873. These data were used to underwrite a clinical assessment of PF-02413873
      in a randomized, double-blinded, third-party open, placebo-controlled, dose
      escalation study in healthy female volunteers with dosing for 14 days. PF
      02413873 blocked the follicular phase increase in endometrial thickness, the
      midcycle lutenizing hormone surge, and elevation in estradiol in a dose-dependent
      fashion compared with placebo. This is the first report of translational efficacy
      data with a nonsteroidal PR antagonist in cynomolgus macaque and human subjects.

PMID- 21849627
TI  - CTEP: a novel, potent, long-acting, and orally bioavailable metabotropic
      glutamate receptor 5 inhibitor.
AB  - The metabotropic glutamate receptor 5 (mGlu5) is a glutamate-activated class C G
      protein-coupled receptor widely expressed in the central nervous system and
      clinically investigated as a drug target for a range of indications, including
      depression, Parkinson's disease, and fragile X syndrome. Here, we present the
      novel potent, selective, and orally bioavailable mGlu5 negative allosteric
      modulator with inverse agonist properties 2-chloro-4-((2,5-dimethyl-1-(4
      (trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP). CTEP binds
      mGlu5 with low nanomolar affinity and shows >1000-fold selectivity when tested
      against 103 targets, including all known mGlu receptors. CTEP penetrates the
      brain with a brain/plasma ratio of 2.6 and displaces the tracer [(3)H]3-(6-methyl
      pyridin-2-ylethynyl)-cyclohex-2-enone-O-methyl-oxime (ABP688) in vivo in mice
      from brain regions expressing mGlu5 with an average ED(50) equivalent to a drug
      concentration of 77.5 ng/g in brain tissue. This novel mGlu5 inhibitor is active
      in the stress-induced hyperthermia procedure in mice and the Vogel conflict
      drinking test in rats with minimal effective doses of 0.1 and 0.3 mg/kg,
      respectively, reflecting a 30- to 100-fold higher in vivo potency compared with 2
      methyl-6-(phenylethynyl)pyridine (MPEP) and fenobam. CTEP is the first reported
      mGlu5 inhibitor with both long half-life of approximately 18 h and high oral
      bioavailability allowing chronic treatment with continuous receptor blockade with
      one dose every 48 h in adult and newborn animals. By enabling long-term treatment
      through a wide age range, CTEP allows the exploration of the full therapeutic
      potential of mGlu5 inhibitors for indications requiring chronic receptor
      inhibition.

PMID- 21849628
TI  - Rivalry between afterimages and real images: the influence of the percept and the
      eye.
AB  - In binocular rivalry, the conscious percept alternates stochastically between two
      images shown to the two eyes. Both suppressed and dominant images form
      afterimages (AIs) whose strength depends on the perceptual state during
      induction. Counterintuitively, when these two AIs rival, the AI of the previously
      suppressed percept gains initial dominance, even when it is weaker. Here, we
      examined rivalry between afterimages, between real images, and between both to
      examine eye-based and binocular contributions to this effect. In all experiments,
      we found that for both AIs and real images, the suppressed percept consistently
      gained initial dominance following a long suppression period. Dominance reversals
      failed to occur following short suppression periods and depended on an abrupt
      change (removal) of the stimulus. With real images, results were replicated also
      when eye channels were exchanged during the abrupt change. The initial dominance
      of the weaker, previously suppressed percept is thus not due to its weaker
      contrast, to it being an afterimage, or to monocular adaptation effects as
      previously suggested. Instead, it is due to binocular, higher level effects that
      favor a perceptual switch after prolonged dominance. We discuss a plausible
      neural account for these findings in terms of neural interactions between
      binocular and eye-related stages.

PMID- 21849629
TI  - Stereo improves 3D shape discrimination even when rich monocular shape cues are
      available.
AB  - We measured the ability to discriminate 3D shapes across changes in viewpoint and
      illumination based on rich monocular 3D information and tested whether the
      addition of stereo information improves shape constancy. Stimuli were images of
      smoothly curved, random 3D objects. Objects were presented in three viewing
      conditions that provided different 3D information: shading-only, stereo-only, and
      combined shading and stereo. Observers performed shape discrimination judgments
      for sequentially presented objects that differed in orientation by rotation of 0
      degrees -60 degrees  in depth. We found that rotation in depth markedly impaired
      discrimination performance in all viewing conditions, as evidenced by reduced
      sensitivity (d') and increased bias toward judging same shapes as different. We
      also observed a consistent benefit from stereo, both in conditions with and
      without change in viewpoint. Results were similar for objects with purely
      Lambertian reflectance and shiny objects with a large specular component. Our
      results demonstrate that shape perception for random 3D objects is highly
      viewpoint-dependent and that stereo improves shape discrimination even when rich
      monocular shape cues are available.

PMID- 21849631
TI  - Control of microvascular PO2 kinetics following onset of muscle contractions:
      role for AMPK.
AB  - The microvascular partial pressure of oxygen (Pmv(o(2))) kinetics following the
      onset of exercise reflects the relationship between muscle O(2) delivery and
      uptake (Vo(2)). Although AMP-activated protein kinase (AMPK) is known as a
      regulator of mitochondria and nitric oxide metabolism, it is unclear whether the
      dynamic balance of O(2) delivery and Vo(2) at exercise onset is dependent on AMPK
      activation level. We used transgenic mice with muscle-specific AMPK dominant
      negative (AMPK-DN) to investigate a role for skeletal muscle AMPK on Pmv(o(2))
      kinetics following onset of muscle contractions. Phosphorescence quenching
      techniques were used to measure Pmv(o(2)) at rest and across the transition to
      twitch (1 Hz) and tetanic (100 Hz, 3-5 V, 4-ms pulse duration, stimulus duration
      of 100 ms every 1 s for 1 min) contractions in gastrocnemius muscles (each group
      n = 6) of AMPK-DN mice and wild-type littermates (WT) under isoflurane anesthesia
      with 100% inspired O(2) to avoid hypoxemia. Baseline Pmv(o(2)) before
      contractions was not different between groups (P > 0.05). Both muscle contraction
      conditions exhibited a delay followed by an exponential decrease in Pmv(o(2)).
      However, compared with WT, AMPK-DN demonstrated 1) prolongation of the time delay
      before Pmv(o(2)) began to decline (1 Hz: WT, 3.2 +/- 0.5 s; AMPK-DN, 6.5 +/- 0.4
      s; 100 Hz: WT, 4.4 +/- 1.0 s; AMPK-DN, 6.5 +/- 1.4 s; P < 0.05), 2) a faster
      response time (i.e., time constant; 1 Hz: WT, 19.4 +/- 3.9 s; AMPK-DN, 12.4 +/-
      2.6 s; 100 Hz: WT, 15.1 +/- 2.2 s; AMPK-DN, 9.0 +/- 1.7 s; P < 0.05). These
      findings are consistent with the presence of substantial mitochondrial and
      microvascular dysfunction in AMPK-DN mice, which likely slows O(2) consumption
      kinetics (i.e., oxidative phosphorylation response) and impairs the hyperemic
      response at the onset of contractions thereby sowing the seeds for exercise
      intolerance.

PMID- 21849630
TI  - Augmented central nitric oxide production inhibits vasopressin release during
      hemorrhage in acute alcohol-intoxicated rodents.
AB  - Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage,
      contributing to impaired hemodynamic counter-regulation. This can be restored by
      central cholinergic stimulation, implicating disrupted signaling regulating AVP
      release. AVP is released in response to hemorrhage and hyperosmolality. Studies
      have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release.
      AAI has been shown to increase NO content in the paraventricular nucleus. We
      hypothesized that the attenuated AVP response to hemorrhage during AAI is the
      result of increased central NO inhibition. In addition, we predicted that the
      increased NO tone during AAI would impair the AVP response to hyperosmolality.
      Conscious male Sprague-Dawley rats (300-325 g) received a 15-h intragastric
      infusion of alcohol (2.5 g/kg + 300 mg.kg(-1).h(-1)) or dextrose prior to a 60
      min fixed-pressure hemorrhage (~40 mmHg) or 5% hypertonic saline infusion (0.05
      ml.kg(-1).min(-1)). AAI attenuated the AVP response to hemorrhage, which was
      associated with increased paraventricular NO content. In contrast, AAI did not
      impair the AVP response to hyperosmolality. This was accompanied by decreased
      paraventricular NO content. To confirm the role of NO in the alcohol-induced
      inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor,
      nitro-l-arginine methyl ester (l-NAME; 250 MUg/5 MUl), was administered centrally
      prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage
      in dextrose-treated animals; however, it restored the AVP response during AAI.
      These results indicate that AAI impairs the AVP response to hemorrhage, while not
      affecting the response to hyperosmolality. Furthermore, these data demonstrate
      that the attenuated AVP response to hemorrhage is the result of augmented central
      NO inhibition.

PMID- 21849632
TI  - Early functional muscle regeneration after myotoxic injury in mice is unaffected
      by nNOS absence.
AB  - Nitric oxide (NO) is an important signaling molecule produced in skeletal muscle
      primarily via the neuronal subtype of NO synthase (NOS1, or nNOS). While many
      studies have reported NO production to be important in muscle regeneration, none
      have examined the contribution of nNOS-derived NO to functional muscle
      regeneration (i.e., restoration of the muscle's ability to produce force) after
      acute myotoxic injury. In the present study, we tested the hypothesis that
      genetic deletion of nNOS would impair functional muscle regeneration after
      myotoxic injury in nNOS(-/-) mice. We found that nNOS(-/-) mice had lower body
      mass, lower muscle mass, and smaller myofiber cross-sectional area and that their
      tibialis anterior (TA) muscles produced lower absolute tetanic forces than those
      of wild-type littermate controls but that normalized or specific force was
      identical between the strains. In addition, muscles from nNOS(-/-) mice were more
      resistant to fatigue than those of wild-type littermates (P < 0.05). To determine
      whether deletion of nNOS affected muscle regeneration, TA muscles from nNOS(-/-)
      mice and wild-type littermates were injected with the myotoxin notexin to cause
      complete fiber degeneration, and muscle structure and function were assessed at 7
      and 10 days postinjury. Myofiber cross-sectional area was lower in regenerating
      nNOS(-/-) mice than wild-type controls at 7 and 10 days postinjury; however,
      contrary to our original hypothesis, no difference in force-producing capacity of
      the TA muscle was evident between the two groups at either time point. Our
      findings reveal that nNOS is not essential for functional muscle regeneration
      after acute myotoxic damage.

PMID- 21849633
TI  - "Liking" and "wanting" of sweet and oily food stimuli as affected by high-fat
      diet-induced obesity, weight loss, leptin, and genetic predisposition.
AB  - Cross-sectional studies in both humans and animals have demonstrated associations
      between obesity and altered reward functions at the behavioral and neural level,
      but it is unclear whether these alterations are cause or consequence of the obese
      state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and
      selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction
      of obesity by high-fat diet feeding and after subsequent loss of excess body
      weight by chronic calorie restriction. As measured by the brief access lick and
      taste-reactivity paradigms, both obese SD and OP rats "liked" low concentrations
      of sucrose and corn oil less, but "liked" the highest concentrations more,
      compared with lean rats, and this effect was fully reversed by weight loss in SD
      rats. Acute food deprivation was unable to change decreased responsiveness to low
      concentrations but eliminated increased responsiveness to high concentrations in
      obese SD rats, and leptin administration in weight-reduced SD rats shifted
      concentration-response curves toward that seen in the obese state in the brief
      access lick test. "Wanting" and reinforcement learning as assessed in the
      incentive runway and progressive ratio lever-pressing paradigms was paradoxically
      decreased in both obese (compared with lean SD rats) and OP (compared with OR
      rats). Thus, reversible, obesity-associated, reduced "liking" and "wanting" of
      low-calorie foods in SD rats suggest a role for secondary effects of the obese
      state on reward functions, while similar differences between select lines of OP
      and OR rats before induction of obesity indicate a genetic component.

PMID- 21849634
TI  - Intrathecal bombesin is sympathoexcitatory and pressor in rat.
AB  - Bombesin, a 14 amino-acid peptide, is pressor when administered intravenously in
      rat and pressor and sympathoexcitatory when applied intracerebroventricularly. To
      determine the spinal effects of bombesin, the peptide was administered acutely in
      the intrathecal space at around thoracic spinal cord level six of urethane
      anesthetized, paralyzed, and bilaterally vagotomized rats. Blood pressure, heart
      rate, splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, and
      end-tidal CO(2) were monitored to evaluate changes in the cardiorespiratory
      systems. Bombesin elicited a long-lasting excitation of sSNA associated with an
      increase in blood pressure and tachycardia. There was a mean increase in arterial
      blood pressure of 52 +/- 5 mmHg (300 MUM; P < 0.01). Heart rate and sSNA also
      increased by 40 +/- 4 beats/min (P < 0.01) and 162 +/- 33% (P < 0.01),
      respectively. Phrenic nerve amplitude (PNamp, 73 +/- 8%, P < 0.01) and phrenic
      expiratory period (+0.16 +/- 0.02 s, P < 0.05) increased following 300 MUM
      bombesin. The gain of the sympathetic baroreflex increased from -2.8 +/- 0.7 to 
      5.4 +/- 0.9% (P < 0.01), whereas the sSNA range was increased by 99 +/- 26% (P <
      0.01). During hyperoxic hypercapnia (10% CO(2) in O(2), 90 s), bombesin
      potentiated the responses in heart rate (-25 +/- 5 beats/min, P < 0.01) and sSNA
      (+136 +/- 29%, P < 0.001) but reduced PNamp (from 58 +/- 6 to 39 +/- 7%, P <
      0.05). Finally, ICI-216,140 (1 mM), an in vivo antagonist for the bombesin
      receptor 2, attenuated the effects of 300 MUM bombesin on blood pressure (21 +/-
      7 mmHg, P < 0.01). We conclude that bombesin is sympathoexcitatory at thoracic
      spinal segments. The effect on phrenic nerve activity may the result of
      spinobulbar pathways and activation of local motoneuronal pools.

PMID- 21849635
TI  - Chronic heart failure selectively induces regional heterogeneity of insulin
      responsive glucose transporters.
AB  - Glucose uptake across the sarcolemma is regulated by a family of membrane
      proteins called glucose transporters (GLUTs), which includes GLUT4 (the major
      cardiac isoform) and GLUT12 (a novel, second insulin-sensitive isoform).
      Potential regional patterns in glucose transport across the cardiac chambers have
      not been examined; thus, we hypothesized that insulin-responsive GLUT4 and -12
      protein and gene expression would be chamber specific in healthy subjects and
      during chronic heart failure (HF). Using a canine model of tachypacing-induced,
      progressive, chronic HF, total GLUT protein and messenger RNA in both ventricles
      and atria (free wall and appendage) were investigated by immunoblotting and real
      time PCR. In controls, GLUT4, but not GLUT12, protein content was significantly
      higher in the atria compared with the ventricles, with the highest content in the
      right atrium (RA; P < 0.001). GLUT4 and GLUT12 mRNA levels were similar across
      the cardiac chambers. During chronic HF, GLUT4 and GLUT12 protein content was
      highest in the left ventricle (LV; by 2.5- and 4.2-fold, respectively, P < 0.01),
      with a concomitant increase in GLUT4 and GLUT12 mRNA (P < 0.001). GLUT4, but not
      GLUT12, protein content was decreased in RA during chronic HF (P = 0.001). In
      conclusion, GLUT4 protein was differentially expressed across the chambers in the
      healthy heart, and this regional pattern was reversed during HF. Our data suggest
      that LV was the primary site dependent on both GLUT4 and GLUT12 during chronic
      HF. In addition, the paradoxical decrease in GLUT4 content in RA may induce
      perturbations in atrial energy production during chronic HF.

PMID- 21849636
TI  - The common hepatic branch of the vagus is not required to mediate the glycemic
      and food intake suppressive effects of glucagon-like-peptide-1.
AB  - The incretin and food intake suppressive effects of intraperitoneally
      administered glucagon-like peptide-1 (GLP-1) involve activation of GLP-1
      receptors (GLP-1R) expressed on vagal afferent fiber terminals. Central nervous
      system processing of GLP-1R-driven vagal afferents results in satiation signaling
      and enhanced insulin secretion from pancreatic-projecting vagal efferents. As the
      vast majority of endogenous GLP-1 is released from intestinal l-cells following
      ingestion, it stands to reason that paracrine GLP-1 signaling, activating
      adjacent GLP-1R expressed on vagal afferent fibers of gastrointestinal origin,
      contributes to glycemic and food intake control. However, systemic GLP-1R
      mediated control of glycemia is currently attributed to endocrine action
      involving GLP-1R expressed in the hepatoportal bed on terminals of the common
      hepatic branch of the vagus (CHB). Here, we examine the hypothesis that
      activation of GLP-1R expressed on the CHB is not required for GLP-1's glycemic
      and intake suppressive effects, but rather paracrine signaling on non-CHB vagal
      afferents is required to mediate GLP-1's effects. Selective CHB ablation (CHBX),
      complete subdiaphragmatic vagal deafferentation (SDA), and surgical control rats
      received an oral glucose tolerance test (2.0 g glucose/kg) 10 min after an
      intraperitoneal injection of the GLP-1R antagonist, exendin-(9-39) (Ex-9; 0.5
      mg/kg) or vehicle. CHBX and control rats showed comparable increases in blood
      glucose following blockade of GLP-1R by Ex-9, whereas SDA rats failed to show a
      GLP-1R-mediated incretin response. Furthermore, GLP-1(7-36) (0.5 mg/kg ip)
      produced a comparable suppression of 1-h 25% glucose intake in both CHBX and
      control rats, whereas intake suppression in SDA rats was blunted. These findings
      support the hypothesis that systemic GLP-1R mediation of glycemic control and
      food intake suppression involves paracrine-like signaling on GLP-1R expressed on
      vagal afferent fibers of gastrointestinal origin but does not require the CHB.

PMID- 21849638
TI  - Chemokines and stroke: the subcellular harbingers of apoplexy?

PMID- 21849637
TI  - Chronic tempol treatment attenuates the renal hemodynamic effects induced by a
      heme oxygenase inhibitor in streptozotocin diabetic rats.
AB  - Heme oxygenase-1 (HO-1) is induced by oxidative stress and plays an important
      role in protecting the kidney from oxidant-mediated damage in the streptozotocin
      (STZ) rat model of type-1 diabetes mellitus (DM-1). HO-derived metabolites,
      presumably carbon monoxide (CO), mediate vasodilatory influences in the renal
      circulation, particularly in conditions linked to elevated HO-1 protein
      expression or diminished nitric oxide (NO) levels. We tested the hypothesis that
      diabetes increases oxidative stress and induces HO-1 protein expression, which
      contributes to regulate renal hemodynamics in conditions of low NO
      bioavailability. Two weeks after the induction of diabetes with STZ (65 mg/kg
      iv), Sprague-Dawley rats exhibited higher renal HO-1 protein expression,
      hyperglycemia, and elevated renal nitrotyrosine levels than control normoglycemic
      animals. In anesthetized diabetic rats, renal vascular resistance (RVR) was
      increased, and in vivo cortical NO levels were reduced (P < 0.05) compared with
      control animals. Acute administration of the HO inhibitor Stannous mesoporphyrin
      (SnMP; 40 MUmol/kg iv) did not alter renal hemodynamics in control rats, but
      greatly decreased glomerular filtration rate and renal blood flow, markedly
      increasing RVR in hyperglycemic diabetic rats. Chronic oral treatment with the
      SOD mimetic tempol prevented the elevation of nitrotyrosine, the HO-1 protein
      induction, and the increases in RVR induced by SnMP in the diabetic group,
      without altering basal NO concentrations or RVR. Increasing concentrations of a
      CO donor (CO-releasing molecule-A1) on pressurized renal interlobar arteries
      elicited a comparable relaxation in vessels taken from control or diabetic
      animals. These results suggest that oxidative stress-induced HO-1 exerts
      vasodilatory actions that partially maintain renal hemodynamics in uncontrolled
      DM-1.

PMID- 21849639
TI  - Time to reevaluate the role of venous hemodynamics in MS pathophysiology?:
      Controversy mounts.

PMID- 21849640
TI  - Stroke recurrence within the time window recommended for carotid endarterectomy.
AB  - OBJECTIVE: In the North Dublin Population Stroke Study, we investigated the risk
      of recurrent stroke within the 14-day time window recommended for endarterectomy.
      METHODS: In a population-based prospective cohort study, all ischemic stroke
      patients were identified over 1 year and categorized into those with (CS
      positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (>=50%
      lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and
      7 and 14 days. RESULTS: Of 365 ischemic stroke patients with carotid imaging, 51
      were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral
      carotid occlusion, or intracranial stenosis, leaving 314 included for analysis
      (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS
      positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset (p
      =0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients (p =0.01)
      by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients
      by 14 days (p =0.02). On multivariable Cox regression analysis, CS was the only
      independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1,
      95% confidence interval [CI] 1.6-837.5, p =0.03), and 7 days (HR 9.1, 1.1-79.2, p
      =0.05), with a trend at 14 days (HR 4.6, 0.9-22.8, p =0.06). CONCLUSIONS:
      Although only a minority of patients with symptomatic CS had a recurrent stroke
      within 14 days, early recurrent stroke risk was high, particularly within the
      first 72 hours. Earlier carotid revascularization or improved acute medical
      treatment may reduce recurrence in this high-risk group.

PMID- 21849641
TI  - Network correlates of the cognitive response to levodopa in Parkinson disease.
AB  - OBJECTIVE: Cognitive dysfunction is common in Parkinson disease (PD), even early
      in its clinical course. This disease manifestation has been associated with
      impaired verbal learning performance as well as abnormal expression of a specific
      PD-related cognitive spatial covariance pattern (PDCP). It is not known, however,
      how this metabolic network relates to the cognitive response to dopaminergic
      therapy on the individual patient level. METHODS: We assessed treatment-mediated
      changes in verbal learning and PDCP expression in 17 patients with PD without
      dementia who underwent cognitive testing and metabolic imaging in the unmedicated
      and levodopa-treated conditions. We also determined whether analogous changes
      were present in 12 other patients with PD without dementia who were evaluated
      before and during the treatment of cognitive symptoms with placebo. RESULTS:
      Levodopa-mediated changes in verbal learning correlated with concurrent changes
      in PDCP expression (r = -0.60, p < 0.01). The subset of patients with meaningful
      cognitive improvement on levodopa (n = 8) exhibited concurrent reductions in PDCP
      expression (p < 0.01) with treatment; network modulation was not evident in the
      remaining subjects. Notably, the levodopa cognitive response correlated with
      baseline PDCP levels (r = 0.70, p = 0.002). By contrast, placebo did not affect
      PDCP expression, even in the subjects (n = 7) with improved verbal learning
      during treatment. CONCLUSIONS: These findings suggest that cognitive dysfunction
      in PD may respond to treatment depending upon the degree of baseline PDCP
      expression. Quantification of treatment-mediated network changes can provide
      objective information concerning the efficacy of new agents directed at the
      cognitive manifestations of this disease.

PMID- 21849642
TI  - High-risk asymptomatic carotid stenosis: ulceration on 3D ultrasound vs TCD
      microemboli.
AB  - OBJECTIVE: We compared microemboli on transcranial Doppler (TCD) with carotid
      ulcerations on 3D ultrasound (US) as an additional method for identifying the
      small proportion of patients with asymptomatic carotid stenosis (ACS) who can
      benefit from revascularization such as endarterectomy or stenting. METHODS:
      Patients with ACS (n = 253) with carotid stenosis >60% by Doppler ultrasound were
      studied prospectively with TCD embolus detection and 3D US to detect ulcers (the
      total number of ulcers in both internal carotids) and followed for 3 years.
      RESULTS: Mean age was 69.66 (SD 8.51) years; 11 (4%) had >=3 ulcers (Ulcer 3), 11
      (6%) had microemboli, and 25 (10%) had microemboli or >=3 ulcers. Ulcer 3
      patients were more likely to have a stroke or death in 3 years (18% vs 2%; p =
      0.03), regardless of the side on which the ulcers were found. The 3-year risk of
      stroke or death was 20% with microemboli vs 2% without (p = 0.003). The annual
      rate of ipsilateral stroke was 0.8%. CONCLUSION: Adding 3D US detection of ulcers
      doubles (to 10%) the proportion of patients with ACS who may benefit from
      endarterectomy or stenting. However, until 3-year event rates of stroke or death
      with endarterectomy or stenting reach <2%, 90% of patients with ACS would be
      better treated medically until they develop symptoms, ulcers, or emboli.

PMID- 21849643
TI  - Retinal microvascular changes and subsequent vascular events after ischemic
      stroke.
AB  - OBJECTIVES: Retinal microvasculature changes are associated with vascular events
      including stroke in healthy populations. It is not known whether retinal
      microvascular changes predict recurrent vascular events after ischemic stroke. We
      examined the relationship between retinal microvascular signs and subsequent
      vascular events in a prospective cohort of 652 acute ischemic stroke patients
      admitted to a tertiary hospital in Singapore from 2005 to 2007. METHODS: Retinal
      photographs taken within 1 week of stroke onset were assessed in a masked manner
      for quantitative and qualitative measures. Follow-up data over 2-4 years were
      obtained by standardized telephone interview and then were verified from medical
      records. Predictors of recurrent vascular events (cerebrovascular, coronary,
      vascular death, and composite vascular events) were determined using Cox
      regression models. RESULTS: Follow-up data over a median of 29 months were
      obtained for 89% (652 patients) of the cohort. After adjustment for covariates
      including traditional risk factors and index stroke etiology, patients with
      severe arteriovenous nicking (AVN) were more likely to have a recurrent
      cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20
      4.33) compared with those without AVN. Patients with severe focal arteriolar
      narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR
      2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI
      1.31-5.86) compared to those without FAN. CONCLUSIONS: Retinal microvascular
      changes predicted subsequent vascular events after ischemic stroke, independent
      of traditional risk factors and stroke subtype. Thus, retinal imaging has a
      potential role in predicting the risk of recurrent vascular events after ischemic
      stroke and in understanding novel vascular risk factors.

PMID- 21849644
TI  - Normal pressure hydrocephalus: how often does the diagnosis hold water?
AB  - OBJECTIVE: To determine our community's incidence of clinically suspected normal
      pressure hydrocephalus (NPH), the rate of shunting for NPH, and short- and long
      term outcomes of shunting. METHODS: A retrospective query of the Mayo Clinic
      medical records linkage system was conducted to identify residents of Olmsted
      County, Minnesota, undergoing an invasive diagnostic procedure for evaluation of
      suspected NPH from 1995 through 2003. Among patients with shunts, early- and long
      term outcomes were determined via a review of available medical records. RESULTS:
      Forty-one patients underwent an invasive diagnostic procedure for evaluation of
      suspected NPH; 13 ultimately received shunts, representing an incidence of
      1.19/100,000/year. The incidence of sustained definite improvements at 3 years
      after shunting was only 0.36/100,000/year. Definite gait improvement was
      documented in 75% at 3-6 months after shunt placement, although it dropped to 50%
      at 1 year and to 33% at 3 years. Only 1 of 8 patients with cognitive impairment
      and 1 of 6 patients with urinary incontinence had definite improvement in these
      symptoms at 3 years. No patient with moderate to severe postural instability
      experienced sustained definite improvement in any symptom. Complications occurred
      in 33% of patients including one perioperative death. Additional or alternative
      neurologic diagnoses later surfaced in 5 of 12 patients. CONCLUSIONS: In this
      community, NPH is relatively rare with an incidence approximating that of
      progressive supranuclear palsy in this population. Whereas early gait improvement
      was common, only one-third of patients enjoyed continued improvement by 3 years;
      cognition or urinary incontinence was even less responsive long term. Baseline
      postural instability predicted poor outcome. Clinicians should balance potential
      benefits of shunting against the known risks.

PMID- 21849645
TI  - Inclusion of RBD improves the diagnostic classification of dementia with Lewy
      bodies.
AB  - OBJECTIVE: To determine whether adding REM sleep behavior disorder (RBD) to the
      dementia with Lewy bodies (DLB) diagnostic criteria improves classification
      accuracy of autopsy-confirmed DLB. METHODS: We followed 234 consecutive patients
      with dementia until autopsy with a mean of 4 annual visits. Clinical diagnoses
      included DLB, Alzheimer disease (AD), corticobasal syndrome, and frontotemporal
      dementia. Pathologic diagnoses used the 2005 DLB consensus criteria and included
      no/low likelihood DLB (non-DLB; n = 136) and intermediate/high likelihood DLB
      (DLB; n = 98). Regression modeling and sensitivity/specificity analyses were used
      to evaluate the diagnostic role of RBD. RESULTS: Each of the 3 core features
      increased the odds of autopsy-confirmed DLB up to 2-fold, and RBD increased the
      odds by 6-fold. When clinically probable DLB reflected dementia and 2 or more of
      the 3 core features, sensitivity was 85%, and specificity was 73%. When RBD was
      added and clinically probable DLB reflected 2 or more of 4 features, sensitivity
      improved to 88%. When dementia and RBD were also designated as probable DLB,
      sensitivity increased to 90% while specificity remained at 73%. The VH,
      parkinsonism, RBD model lowered sensitivity to 83%, but improved specificity to
      85%. CONCLUSIONS: Inclusion of RBD as a core clinical feature improves the
      diagnostic accuracy of autopsy-confirmed DLB.

PMID- 21849646
TI  - Altered functional connectivity in asymptomatic MAPT subjects: a comparison to
      bvFTD.
AB  - OBJECTIVE: To determine whether functional connectivity is altered in subjects
      with mutations in the microtubule associated protein tau (MAPT) gene who were
      asymptomatic but were destined to develop dementia, and to compare these findings
      to those in subjects with behavioral variant frontotemporal dementia (bvFTD).
      METHODS: In this case-control study, we identified 8 asymptomatic subjects with
      mutations in MAPT and 8 controls who screened negative for mutations in MAPT.
      Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and
      matched to 21 controls. All subjects had resting-state fMRI. In-phase functional
      connectivity was assessed between a precuneus seed in the default mode network
      (DMN) and a fronto-insular cortex seed in the salience network, and the rest of
      the brain. Atlas-based parcellation was used to assess functional connectivity
      and gray matter volume across specific regions of interest. RESULTS: The
      asymptomatic MAPT subjects and subjects with bvFTD showed altered functional
      connectivity in the DMN, with reduced in-phase connectivity in lateral temporal
      lobes and medial prefrontal cortex, compared to controls. Increased in-phase
      connectivity was also observed in both groups in the medial parietal lobe. Only
      the bvFTD group showed altered functional connectivity in the salience network,
      with reduced connectivity in the fronto-insular cortex and anterior cingulate.
      Gray matter loss was observed across temporal, frontal, and parietal regions in
      bvFTD, but not in the asymptomatic MAPT subjects. CONCLUSIONS: Functional
      connectivity in the DMN is altered in MAPT subjects before the occurrence of both
      atrophy and clinical symptoms, suggesting that changes in functional connectivity
      are early features of the disease.

PMID- 21849648
TI  - Carotid stenosis: to revascularize, or not to revascularize: that is the
      question.

PMID- 21849649
TI  - Normal pressure hydrocephalus: measure twice, shunt once.

PMID- 21849647
TI  - Interferon beta-1b-neutralizing antibodies 5 years after clinically isolated
      syndrome.
AB  - OBJECTIVE: To determine the frequency and consequences of neutralizing antibodies
      (NAbs) in patients with a first event suggestive of multiple sclerosis (MS)
      treated with interferon beta-1b (IFNbeta-1b). METHODS: In the Betaseron/Betaferon
      in Newly Emerging MS For Initial Treatment (BENEFIT) study, patients were
      randomly assigned to 250 MUg IFNbeta-1b (Betaferon) or placebo subcutaneously
      every other day for 2 years or until diagnosis of clinically definite MS (CDMS).
      Patients were then offered open-label IFNbeta-1b for up to 5 years. NAb status
      was assessed every 6 months by the myxovirus protein A induction assay. A titer
      >20 NU/mL was considered NAb-positive, with low (>=20-100 NU/mL), medium (>=100
      400 NU/mL), and high (>=400 NU/mL) titer categories. Here we examine early
      treated patients, who received IFNbeta-1b for up to 5 years. RESULTS: NAbs were
      measured in 277 of 292 early-treated patients and detected at least once in 88
      (31.8%) patients, with 53 (60.2%) reverting to NAb negativity by year 5. Time to
      CDMS, time to confirmed disability progression, and annualized relapse rate did
      not differ between NAb-positive and NAb-negative patients or between periods of
      NAb positivity vs NAb negativity within patients. Increases in newly active
      lesion number and T2 lesion volume and conversion to McDonald MS were associated
      with NAb positivity and were more pronounced with higher titers. CONCLUSIONS:
      Although NAb positivity was associated with increased brain MRI activity, no
      discernible effects on clinical outcomes were found. This finding may reflect the
      greater power of MRI compared with clinical outcomes to detect the treatment
      effects of IFNbeta-1b and may also result from temporal changes in NAb titers and
      biology.

PMID- 21849650
TI  - IV thrombolysis and statins.
AB  - OBJECTIVE: To examine whether prior statin use affects outcome and intracranial
      hemorrhage (ICH) rates in stroke patients receiving IV thrombolysis (IVT).
      METHODS: In a pooled observational study of 11 IVT databases, we compared
      outcomes between statin users and nonusers. Outcome measures were excellent 3
      month outcome (modified Rankin scale 0-1) and ICH in 3 categories. We
      distinguished all ICHs (ICH(all)), symptomatic ICH based on the criteria of the
      ECASS-II trial (SICH(ECASS-II)), and symptomatic ICH based on the criteria of the
      National Institute of Neurological Disorders and Stroke (NINDS) trial
      (SICH(NINDS)). Unadjusted and adjusted odds ratios (OR) with 95% confidence
      intervals were calculated. RESULTS: Among 4,012 IVT-treated patients, 918 (22.9%)
      were statin users. They were older, more often male, and more frequently had
      hypertension, hypercholesterolemia, diabetes, coronary heart disease, and
      concomitant antithrombotic use compared with nonusers. Fewer statin users (35.5%)
      than nonusers (39.7%) reached an excellent 3-month outcome (OR(unadjusted) 0.84
      [0.72-0.98], p = 0.02). After adjustment for age, gender, blood pressure, time to
      thrombolysis, and stroke severity, the association was no longer significant
      (0.89 [0.74-1.06], p = 0.20). ICH occurred by trend more often in statin users
      (ICH(all) 20.1% vs 17.4%; SICH(NINDS) 9.2% vs 7.5%; SICH(ECASS-II) 6.9% vs 5.1%).
      This difference was statistically significant only for SICH(ECASS-II) (OR = 1.38
      [1.02-1.87]). After adjustment for age, gender, blood pressure, use of
      antithrombotics, and stroke severity, the OR(adjusted) for each category of ICH
      (ICH(all) 1.15 [0.93-1.41]; SICH(ECASS-II) 1.32 [0.94-1.85]; SICH(NINDS) 1.16
      [0.87-1.56]) showed no difference between statin users and nonusers. CONCLUSION:
      In stroke patients receiving IVT, prior statin use was neither an independent
      predictor of functional outcome nor ICH. It may be considered as an indicator of
      baseline characteristics that are associated with a less favorable course.

PMID- 21849652
TI  - Superior canal dehiscence causes abnormal vestibular bone-conducted tuning.

PMID- 21849651
TI  - Systemic chemokine levels, coronary heart disease, and ischemic stroke events:
      the PRIME study.
AB  - OBJECTIVES: To quantify the association between systemic levels of the chemokine
      regulated on activation normal T-cell expressed and secreted (RANTES/CCL5),
      interferon-gamma-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant
      protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease
      (CHD) and ischemic stroke events and to assess their usefulness for CHD and
      ischemic stroke risk prediction in the PRIME Study. METHODS: After 10 years of
      follow-up of 9,771 men, 2 nested case-control studies were built including 621
      first CHD events and 1,242 matched controls and 95 first ischemic stroke events
      and 190 matched controls. Standardized hazard ratios (HRs) for each log
      transformed chemokine were estimated by conditional logistic regression. RESULTS:
      None of the 4 chemokines were independent predictors of CHD, either with respect
      to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70;
      95% confidence interval [CI] 1.05-2.74), IP-10 (HR = 1.53; 95% CI 1.06-2.20), and
      eotaxin-1 (HR = 1.59; 95% CI 1.02-2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68
      1.46), were associated with ischemic stroke independently of traditional
      cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines
      were included in the same multivariate model, RANTES and IP-10 remained
      predictive of ischemic stroke. Their addition to a traditional risk factor model
      predicting ischemic stroke substantially improved the C-statistic from 0.6756 to
      0.7425 (p = 0.004). CONCLUSIONS: In asymptomatic men, higher systemic levels of
      RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD
      events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk
      prediction over traditional risk factors.

PMID- 21849653
TI  - Extracranial venous hemodynamics in multiple sclerosis: a case-control study.
AB  - OBJECTIVES: A chronic state of impaired cerebral and cervical venous drainage,
      termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been
      implicated in the pathogenesis of multiple sclerosis (MS). We performed a color
      coded Doppler sonography case-control study to externally validate the CCSVI
      criteria. METHODS: We prospectively evaluated consecutive patients with
      clinically definite MS and healthy volunteers using extracranial and transcranial
      color-coded Doppler sonography. The recently developed neurosonology criteria for
      CCSVI detection were used for interpretation of ultrasound assessments. The
      presence of venous reflux in cervical veins was assessed both in the sitting and
      upright position during a short period of apnea and after Valsalva maneuver.
      RESULTS: We recruited 42 patients with MS (mean age 39 +/- 11 years, 17 men) and
      43 control individuals (mean age 38 +/- 12 years, 16 men). Very good/excellent
      intrarater and interrater agreement (kappa values 0.82-1.00) was documented in 3
      out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable
      Doppler flow in cervical veins in patients and controls. Reflux in internal
      jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%),
      both in sitting and supine posture during apnea. After performing Valsalva
      maneuver, we documented the presence of IJV valve incompetence in 3 patients with
      MS (7%) and 4 healthy volunteers (9%; p > 0.999). CONCLUSIONS: With established
      reproducibility of venous ultrasound testing, our data argue against CCSVI as the
      underlying mechanism of MS. Without further independent validation of CCSVI,
      potentially dangerous endovascular procedures, proposed as novel therapy for MS,
      should not be performed outside controlled clinical trials.

PMID- 21849654
TI  - Short-acting nifedipine and risk of stroke in elderly hypertensive patients.
AB  - OBJECTIVES: Short-acting nifedipine is frequently prescribed in elderly
      hypertensive patients, despite warnings of possible harmful cardiovascular
      effects. We conducted a case-crossover study to estimate the risk of stroke
      episodes associated with use of short-acting nifedipine in elderly hypertensive
      patients. METHODS: We used the Korea Health Insurance Review & Assessment Service
      database. Cases included elderly hypertensive patients with hospitalization or
      emergency department visits for first stroke (International Classification of
      Diseases-10, I60-I64) between July 1, 2005, and June 30, 2006. Patients with
      prior stroke-related hospital admission or any visit related to TIA were
      excluded. Exposure to a short-acting nifedipine formulation was assessed within 7
      days before the incident stroke episode (case period) and within a 7-day period
      preceding 60 days before the episode (control period). Odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated by conditional logistic regression,
      with adjusting for antihypertensives, anticoagulants, antiplatelet agents, and
      pneumonia. RESULTS: A total of 16,069 stroke patients with a mean (+/-SD) age of
      68.3 (+/-2.1) years were studied, of whom 8,573 (53.3%) were female. Short-acting
      nifedipine was prescribed at least once to 301 (1.9%) patients during the case
      period. An increased risk of stroke associated with use of short-acting
      nifedipine within 7 days (adjusted OR 2.56; 95% CI 1.96-3.37) was observed.
      Patients who were newly prescribed nifedipine within the recent 7 days showed an
      OR of 4.17 (95% CI 2.93-5.93) compared with nonusers. CONCLUSION: Use of short
      acting nifedipine was associated with increased risk of stroke occurrence in
      elderly hypertensive patients.

PMID- 21849655
TI  - Converging PET and fMRI evidence for a common area involved in human focal
      epilepsies.
AB  - OBJECTIVES: Experiments in animal models have identified specific subcortical
      anatomic circuits, which are critically involved in the pathogenesis and control
      of seizure activity. However, whether such anatomic substrates also exist in
      human epilepsy is not known. METHODS: We studied 2 separate groups of patients
      with focal epilepsies arising from any cortical location using either
      simultaneous EEG-fMRI (n = 19 patients) or [11C]flumazenil PET (n = 18). RESULTS:
      Time-locked with the interictal epileptiform discharges, we found significant
      hemodynamic increases common to all patients near the frontal piriform cortex
      ipsilateral to the presumed cortical focus. GABA(A) receptor binding in the same
      area was reduced in patients with more frequent seizures. CONCLUSIONS: Our
      findings of cerebral blood flow and GABAergic changes, irrespective of where
      interictal or ictal activity occurs in the cortex, suggest that this area of the
      human primary olfactory cortex may be an attractive new target for epilepsy
      therapy, including neurosurgery, electrical stimulation, and focal drug delivery.

PMID- 21849656
TI  - Progressive multiple sclerosis is not associated with chronic cerebrospinal
      venous insufficiency.
AB  - OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) had been suggested
      to play a major pathogenetic role in multiple sclerosis (MS), but recent data on
      early stages of MS have not confirmed this theory. Nonetheless, CCSVI could
      represent a late phenomenon of MS or be associated with progression of
      disability. Thus, we studied CCSVI prevalence in primary progressive (PP) and
      secondary progressive (SP) MS, to clarify whether CCSVI characterizes the
      progressive forms of this disease. METHODS: A total of 35 patients with SPMS, 25
      patients with PPMS, and 60 age- and gender-matched normal controls (NC) were
      enrolled into a cross-sectional study. Extracranial and transcranial high
      resolution venous echo color Doppler sonography (ECDS-TCDS) was performed in all
      patients and NC. Those patients having any abnormal ultrasound finding were asked
      to undergo selective venography (VGF). RESULTS: Patients with PPMS (11 women, 14
      men; mean age 47 +/- 11 years) had a disease duration of 11 +/- 7 years and
      Expanded Disability Status Scale (EDSS) score of 6.0 +/- 0.5. Patients with SPMS
      (22 women, 13 men; mean age 45 +/- 14.5 years) had a disease duration of 18 +/-
      14 years and EDSS score of 6.0 +/- 0.8. TCDS was normal in all patients. ECDS
      showed one or more abnormal findings in 9/60 (15.0%) patients (7/35 [20.0%] SPMS,
      2/25 [8.0%] PPMS) and in 14/60 (23.3%) NC (p not significant for all
      comparisons). CCSVI criteria were fulfilled in 0 NC and 4 (6.7%) patients with
      MS: 3 SPMS and 1 PPMS. VGF, performed in 6/9 patients, was abnormal only in one
      case who had bilateral internal jugular vein stenosis. CONCLUSION: Our findings
      indicate that CCSVI is not a late secondary phenomenon of MS and is not
      associated with disability.

PMID- 21849658
TI  - Short-acting nifedipine and risk of stroke.

PMID- 21849657
TI  - Ultrasonic plaque echolucency and emboli signals predict stroke in asymptomatic
      carotid stenosis.
AB  - OBJECTIVES: Better methods are required to identify patients with asymptomatic
      carotid stenosis (ACS) at risk of future stroke. Two potential markers of high
      risk are echolucent plaque morphology on carotid ultrasound and embolic signals
      (ES) in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound
      (TCD). We explored the predictive value of a score based on these 2 measures in
      the prospective, observational, international multicenter Asymptomatic Carotid
      Emboli Study. METHODS: A total of 435 recruited subjects with ACS >=70% had
      baseline ultrasound images and TCD data available. Subjects were prospectively
      followed up for 2 years. RESULTS: A total of 164 (37.7%) plaques were graded as
      echolucent. Plaque echolucency at baseline was associated with an increased risk
      of ipsilateral stroke alone (hazard ratio [HR] 6.43, 95% confidence interval [CI]
      1.36-30.44, p = 0.019). A combined variable of plaque echolucency and ES
      positivity at baseline was associated with a markedly increased risk of
      ipsilateral stroke alone (HR 10.61, 95% CI 2.98-37.82, p = 0.0003). This
      association remained significant after controlling for risk factors, degree of
      carotid stenosis, and antiplatelet medication. CONCLUSIONS: Plaque morphology
      assessed using a simple, and clinically applicable, visual rating scale predicts
      ipsilateral stroke risk in ACS. The combination of ES detection and plaque
      morphology allows a greater prediction than either measure alone and identifies a
      high-risk group with an annual stroke risk of 8%, and a low-risk group with a
      risk of <1% per annum. This risk stratification may prove useful in the selection
      of patients with ACS for endarterectomy.

PMID- 21849659
TI  - Re: Coffee consumption and prostate cancer risk and progression in the health
      professionals follow-up study.

PMID- 21849661
TI  - Evaluating preclinical efficacy.
AB  - Recent disappointing results of clinical trials seeking type 1 diabetes (T1D)
      reversal suggest the need for a reevaluation of our translational efforts. This
      Commentary explores the need for standards in evaluating therapeutic efficacy in
      preclinical models of T1D.

PMID- 21849662
TI  - Biomedical innovation: a risky business at risk.
AB  - Regulatory and financial challenges conspire to stall the development and market
      approval of breakthrough medical products. Inconsistent parameters are used to
      assess the safety and efficacy of drugs, biologics, and devices; this glitch in
      the system introduces uncertainty, slows or blocks product approvals, and
      increases the costs of product development. Here, we consider how to balance the
      benefits and risks to the public in the assessment of innovative medical
      products. We also discuss the Institute of Medicine's recent report on the
      medical device approval process.

PMID- 21849660
TI  - Relationship between statin use and colon cancer recurrence and survival: results
      from CALGB 89803.
AB  - BACKGROUND: Although preclinical and epidemiological data suggest that statins
      may have antineoplastic properties, the impact of statin use on patient survival
      after a curative resection of stage III colon cancer is unknown. METHODS: We
      conducted a prospective observational study of 842 patients with stage III colon
      cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to
      May 2001 to investigate the relationship between statin use and survival. Disease
      free survival (DFS), recurrence-free survival (RFS), and overall survival (OS)
      were investigated by Kaplan-Meier curves and log-rank tests in the overall study
      population and in a subset of patients stratified by KRAS mutation status (n =
      394), and Cox proportional hazards regression was used to assess the simultaneous
      impact of confounding variables. All statistical tests were two-sided. RESULTS:
      Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant
      chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR]
      of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to
      1.49). RFS and OS were also similar between statin users and nonusers (adjusted
      HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death =
      1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of
      increasing duration of statin use before cancer diagnosis (P(trend) = .63, .63,
      and .59 for DFS, RFS, and OS, respectively). The impact of statin use did not
      differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin
      use among mutant and wild-type subgroups (P(interaction) = .84, .67, and .98 for
      DFS, RFS, and OS, respectively). CONCLUSION: Statin use during and after adjuvant
      chemotherapy was not associated with improved DFS, RFS, or OS in patients with
      stage III colon cancer, regardless of KRAS mutation status.

PMID- 21849663
TI  - The emergence of genome-based drug repositioning.
AB  - In a pair of papers in this issue of Science Translational Medicine, Butte et al.
      provide a concrete example of how reinterpreting and comparing genome-wide
      metrics allows us to effectively hypothesize which drugs from one disease
      indication can be repurposed for another disease. The shift toward integrative
      genome-wide computational approaches has precedence in insightful scalar theories
      of biological information. Here, we discuss how this recent work in drug
      repurposing adheres to and takes advantage of the concepts surrounding this
      information paradigm.

PMID- 21849664
TI  - Computational repositioning of the anticonvulsant topiramate for inflammatory
      bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the
      gastrointestinal tract for which there are few safe and effective therapeutic
      options for long-term treatment and disease maintenance. Here, we applied a
      computational approach to discover new drug therapies for IBD in silico, using
      publicly available molecular data reporting gene expression in IBD samples and
      164 small-molecule drug compounds. Among the top compounds predicted to be
      therapeutic for IBD by our approach were prednisolone, a corticosteroid used to
      treat IBD, and topiramate, an anticonvulsant drug not previously described to
      have efficacy for IBD or any related disorders of inflammation or the
      gastrointestinal tract. Using a trinitrobenzenesulfonic acid (TNBS)-induced
      rodent model of IBD, we experimentally validated our topiramate prediction in
      vivo. Oral administration of topiramate significantly reduced gross pathological
      signs and microscopic damage in primary affected colon tissue in the TNBS-induced
      rodent model of IBD. These findings suggest that topiramate might serve as a
      therapeutic option for IBD in humans and support the use of public molecular data
      and computational approaches to discover new therapeutic options for disease.

PMID- 21849665
TI  - Discovery and preclinical validation of drug indications using compendia of
      public gene expression data.
AB  - The application of established drug compounds to new therapeutic indications,
      known as drug repositioning, offers several advantages over traditional drug
      development, including reduced development costs and shorter paths to approval.
      Recent approaches to drug repositioning use high-throughput experimental
      approaches to assess a compound's potential therapeutic qualities. Here, we
      present a systematic computational approach to predict novel therapeutic
      indications on the basis of comprehensive testing of molecular signatures in drug
      disease pairs. We integrated gene expression measurements from 100 diseases and
      gene expression measurements on 164 drug compounds, yielding predicted
      therapeutic potentials for these drugs. We recovered many known drug and disease
      relationships using computationally derived therapeutic potentials and also
      predict many new indications for these 164 drugs. We experimentally validated a
      prediction for the antiulcer drug cimetidine as a candidate therapeutic in the
      treatment of lung adenocarcinoma, and demonstrate its efficacy both in vitro and
      in vivo using mouse xenograft models. This computational method provides a
      systematic approach for repositioning established drugs to treat a wide range of
      human diseases.

PMID- 21849666
TI  - Stem cell-mediated transfer of a human artificial chromosome ameliorates muscular
      dystrophy.
AB  - In contrast to conventional gene therapy vectors, human artificial chromosomes
      (HACs) are episomal vectors that can carry large regions of the genome containing
      regulatory elements. So far, HACs have not been used as vectors in gene therapy
      for treating genetic disorders. Here, we report the amelioration of the
      dystrophic phenotype in the mdx mouse model of Duchenne muscular dystrophy (DMD)
      using a combination of HAC-mediated gene replacement and transplantation with
      blood vessel-associated stem cells (mesoangioblasts). We first genetically
      corrected mesoangioblasts from dystrophic mdx mice with a HAC vector containing
      the entire (2.4 Mb) human dystrophin genetic locus. Genetically corrected
      mesoangioblasts engrafted robustly and gave rise to many dystrophin-positive
      muscle fibers and muscle satellite cells in dystrophic mice, leading to
      morphological and functional amelioration of the phenotype that lasted for up to
      8 months after transplantation. Thus, HAC-mediated gene transfer shows efficacy
      in a preclinical model of DMD and offers potential for future clinical
      translation.

PMID- 21849667
TI  - Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG
      F65S.
AB  - Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the
      heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically
      fragile, with elevated Na and decreased K contents and increased cation channel
      like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited
      increased ouabain and bumetanide-resistant uptake of Li(+) and (86)Rb(+), with
      secondarily increased (86)Rb(+) influx sensitive to ouabain and to bumetanide.
      Increased RhAG-associated (14)C-methylammonium (MA) influx was severely reduced
      in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li(+), (86)Rb(+),
      and (14)C-MA were pharmacologically distinct, and Li(+) uptakes associated with
      RhAG and RhAG F65S were differentially inhibited by NH(4)(+) and Gd(3+). RhAG
      expressing oocytes were acidified and depolarized by 5 mM bath NH(3)/NH(4)(+),
      but alkalinized and depolarized by subsequent bath exposure to 5 mM
      methylammonium chloride (MA/MA(+)). RhAG F65S-expressing oocytes exhibited near
      wild-type responses to NH(4)Cl, but MA/MA(+) elicited attenuated alkalinization
      and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady
      state cation currents unaltered by bath Li(+) substitution or bath addition of 5
      mM NH(4)Cl or MA/MA(+). These oocyte studies suggest that 1) RhAG expression
      increases oocyte transport of NH(3)/NH(4)(+) and MA/MA(+); 2) RhAG F65S exhibits
      gain-of-function phenotypes of increased cation conductance/permeability, and
      loss-of-function phenotypes of decreased and modified MA/MA(+) transport, and
      decreased NH(3)/NH(4)(+)-associated depolarization; and 3) RhAG transports
      NH(3)/NH(4)(+) and MA/MA(+) by distinct mechanisms, and/or the substrates elicit
      distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for
      amine transport. The altered oocyte intracellular pH, membrane potential, and
      currents associated with RhAG or RhAG F65S expression may reflect distinct
      transport mechanisms.

PMID- 21849668
TI  - Bioactive phospholipid signaling influences NHE3-dependent intestinal Na(+) and
      fluid absorption: a macromolecular complex perspective. Focus on
      "Lysophosphatidic acid 5 receptor induces activation of Na(+)/H(+) exchanger 3
      via apical epidermal growth factor receptor in intestinal epithelial cells".

PMID- 21849670
TI  - Differential impact of mitochondrial positioning on mitochondrial Ca(2+) uptake
      and Ca(2+) spark suppression in skeletal muscle.
AB  - Muscle contraction requires ATP and Ca(2+) and, thus, is under direct control of
      mitochondria and the sarcoplasmic reticulum. During postnatal skeletal muscle
      maturation, the mitochondrial network exhibits a shift from a longitudinal
      ("longitudinal mitochondria") to a mostly transversal orientation as a result of
      a progressive increase in mitochondrial association with Ca(2+) release units
      (CRUs) or triads ("triadic mitochondria"). To determine the physiological
      implications of this shift in mitochondrial disposition, we used confocal
      microscopy to monitor activity-dependent changes in myoplasmic (fluo 4) and
      mitochondrial (rhod 2) Ca(2+) in single flexor digitorum brevis (FDB) fibers from
      1- to 4-mo-old mice. A robust and sustained Ca(2+) accumulation in triadic
      mitochondria was triggered by repetitive tetanic stimulation (500 ms, 100 Hz,
      every 2.5 s) in FDB fibers from 4-mo-old mice. Specifically, mitochondrial rhod 2
      fluorescence increased 272 +/- 39% after a single tetanus and 412 +/- 45% after
      five tetani and decayed slowly over 10 min following the final tetanus. Similar
      results were observed in fibers expressing mitochondrial pericam, a mitochondrial
      targeted ratiometric Ca(2+) indicator. Interestingly, sustained mitochondrial
      Ca(2+) uptake following repetitive tetanic stimulation was similar for triadic
      and longitudinal mitochondria in FDB fibers from 1-mo-old mice, and both
      mitochondrial populations were found by electron microscopy to be continuous and
      structurally tethered to the sarcoplasmic reticulum. Conversely, the frequency of
      osmotic shock-induced Ca(2+) sparks per CRU density decreased threefold (from 3.6
      +/- 0.2 to 1.2 +/- 0.1 events.CRU(-1).min(-1).100 MUm(-2)) during postnatal
      development in direct linear correspondence (r(2) = 0.95) to an increase in
      mitochondrion-CRU pairing. Together, these results indicate that mitochondrion
      CRU association promotes Ca(2+) spark suppression but does not significantly
      impact mitochondrial Ca(2+) uptake.

PMID- 21849669
TI  - Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation
      induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal
      epithelial cells.
AB  - Repetitive deformation enhances intestinal epithelial migration across tissue
      fibronectin. We evaluated the contribution of RhoA and its effectors Rho
      associated kinase (ROK/ROCK) and mammalian diaphanous formins (mDia1) to
      deformation-induced intestinal epithelial motility across fibronectin and the
      responsible focal adhesion kinase (FAK), extracellular signal-regulated kinase
      (ERK), p38, and myosin light chain (MLC) signaling. We reduced RhoA, ROCK1,
      ROCK2, and mDia1 by smart-pool double-stranded short-interfering RNAs (siRNA) and
      pharmacologically inhibited RhoA, ROCK, and FAK in human Caco-2 intestinal
      epithelial monolayers on fibronectin-coated membranes subjected to 10% repetitive
      deformation at 10 cycles/min. Migration was measured by wound closure.
      Stimulation of migration by deformation was prevented by exoenzyme C3, Y27632, or
      selective RhoA, ROCK1, and ROCK2 or mDia1 siRNAs. RhoA, ROCK inhibition, or RhoA,
      ROCK1, ROCK2, mDia1, and FAK reduction by siRNA blocked deformation-induced
      nuclear ERK phosphorylation without preventing ERK phosphorylation in the
      cytoplasmic protein fraction. Furthermore, RhoA, ROCK inhibition or RhoA, ROCK1,
      ROCK2, and mDia1 reduction by siRNA also blocked strain-induced FAK-Tyr(925),
      p38, and MLC phosphorylation. These results suggest that RhoA, ROCK, mDia1, FAK,
      ERK, p38, and MLC all mediate the stimulation of intestinal epithelial migration
      by repetitive deformation. This pathway may be an important target for
      interventions to promote mechanotransduced mucosal healing during inflammation.

PMID- 21849671
TI  - Tobacco retail displays: a comparison of industry arguments and retailers'
      experiences.
AB  - BACKGROUND: Tobacco companies have opposed the removal of tobacco retail
      displays, arguing this would compromise retailers' safety, increase retail crime,
      reduce retailers' income, impose additional costs and be inconvenient. These
      arguments have successfully delayed policy development in several jurisdictions.
      METHODS: In-depth interviews conducted with New Zealand retailers who had
      voluntarily removed tobacco from open display in their stores. RESULTS: Retailers
      who had removed tobacco displays did so primarily to reduce their security risk
      and found their stores had become less vulnerable to retail crime. They did not
      find removing displays costly or inconvenient nor had this decision significantly
      reduced their revenue. CONCLUSIONS: Removing in-store tobacco displays may
      increase rather than decrease store safety. Our findings reveal that retailers'
      experiences differed in many ways from tobacco companies' predictions and suggest
      that industry arguments against display removal lack objective support and are
      self-serving.

PMID- 21849672
TI  - Posttranslational modification of gluten shapes TCR usage in celiac disease.
AB  - Posttranslational modification of Ag is implicated in several autoimmune
      diseases. In celiac disease, a cereal gluten-induced enteropathy with several
      autoimmune features, T cell recognition of the gluten Ag is heavily dependent on
      the posttranslational conversion of Gln to Glu residues. Evidence suggests that
      the enhanced recognition of deamidated gluten peptides results from improved
      peptide binding to the MHC and TCR interaction with the peptide-MHC complex. In
      this study, we report that there is a biased usage of TCR Vbeta6.7 chain among
      TCRs reactive to the immunodominant DQ2-alpha-II gliadin epitope. We isolated
      Vbeta6.7 and DQ2-alphaII tetramer-positive CD4(+) T cells from peripheral blood
      of gluten-challenged celiac patients and sequenced the TCRs of a large number of
      single T cells. TCR sequence analysis revealed in vivo clonal expansion,
      convergent recombination, semipublic response, and the notable conservation of a
      non-germline-encoded Arg residue in the CDR3beta loop. Functional testing of a
      prototype DQ2-alpha-II-reactive TCR by analysis of TCR transfectants and soluble
      single-chain TCRs indicate that the deamidated residue in the DQ2-alpha-II
      peptide poses constraints on the TCR structure in which the conserved Arg residue
      is a critical element. The findings have implications for understanding T cell
      responses to posttranslationally modified Ags.

PMID- 21849673
TI  - Caveolin-1 orchestrates TCR synaptic polarity, signal specificity, and function
      in CD8 T cells.
AB  - TCR engagement triggers the polarized recruitment of membrane, actin, and
      transducer assemblies within the T cell-APC contact that amplify and specify
      signaling cascades and T effector activity. We report that caveolin-1, a scaffold
      that regulates polarity and signaling in nonlymphoid cells, is required for
      optimal TCR-induced actin polymerization, synaptic membrane raft polarity, and
      function in CD8, but not CD4, T cells. In CD8(+) T cells, caveolin-1 ablation
      selectively impaired TCR-induced NFAT-dependent NFATc1 and cytokine gene
      expression, whereas caveolin-1 re-expression promoted NFATc1 gene expression.
      Alternatively, caveolin-1 ablation did not affect TCR-induced NF-kappaB-dependent
      Ikappabalpha expression. Cav-1(-/-) mice did not efficiently promote CD8 immunity
      to lymphocytic choriomeningitis virus, nor did cav-1(-/-) OT-1(+) CD8(+) T cells
      efficiently respond to Listeria monocytogenes-OVA after transfer into wild-type
      hosts. Therefore, caveolin-1 is a T cell-intrinsic orchestrator of TCR-mediated
      membrane polarity and signal specificity selectively employed by CD8 T cells to
      customize TCR responsiveness.

PMID- 21849674
TI  - Recognition and killing of human and murine pancreatic beta cells by the NK
      receptor NKp46.
AB  - Type 1 diabetes is an incurable disease that is currently treated by insulin
      injections or in rare cases by islet transplantation. We have recently shown that
      NKp46, a major killer receptor expressed by NK cells, recognizes an unknown
      ligand expressed by beta cells and that in the absence of NKp46, or when its
      activity is blocked, diabetes development is inhibited. In this study, we
      investigate whether NKp46 is involved in the killing of human beta cells that are
      intended to be used for transplantation, and we also thoroughly characterize the
      interaction between NKp46 and its human and mouse beta cell ligands. We show that
      human beta cells express an unknown ligand for NKp46 and are killed in an NKp46
      dependent manner. We further demonstrate that the expression of the NKp46 ligand
      is detected on human beta cells already at the embryonic stage and that it
      appears on murine beta cells only following birth. Because the NKp46 ligand is
      detected on healthy beta cells, we wondered why type 1 diabetes does not develop
      in all individuals and show that NK cells are absent from the vicinity of islets
      of healthy mice and are detected in situ in proximity with beta cells in NOD
      mice. We also investigate the molecular mechanisms controlling NKp46 interactions
      with its beta cell ligand and demonstrate that the recognition is confined to the
      membrane proximal domain and stalk region of NKp46 and that two glycosylated
      residues of NKp46, Thr(125) and Asn(216), are critical for this recognition.

PMID- 21849675
TI  - The transport and inactivation kinetics of bacterial lipopolysaccharide influence
      its immunological potency in vivo.
AB  - The extraordinary potency and pathological relevance of gram-negative bacterial
      LPSs have made them very popular experimental agonists, yet little is known about
      what happens to these stimulatory molecules within animal tissues. We tracked
      fluorescent and radiolabeled LPS from a s.c. inoculation site to its draining
      lymph nodes (DLN), blood, and liver. Although we found FITC-labeled LPS in DLN
      within minutes of injection, drainage of radiolabeled LPS continued for >6 wk.
      Within the DLN, most of the LPS was found in the subcapsular sinus or medulla,
      near or within lymphatic endothelial cells and CD169(+) macrophages. Whereas most
      of the LPS seemed to pass through the DLN without entering B cell follicles, by
      24 h after injection a small amount of LPS was found in the paracortex. In wild
      type mice, >=70% of the injected radiolabeled LPS underwent inactivation by
      deacylation before it left the footpad; in animals that lacked acyloxyacyl
      hydrolase, the LPS-deacylating enzyme, prolonged drainage of fully acylated
      (active) LPS boosted polyclonal IgM and IgG3 Ab titers. LPS egress from a s.c.
      injection site thus occurred during many weeks and was mainly via lymphatic
      channels. Its immunological potency, as measured by its ability to stimulate
      polyclonal Ab production, was greatly influenced by the kinetics of both
      lymphatic drainage and enzymatic inactivation.

PMID- 21849676
TI  - MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN
      gamma pathway, Th1 polarization, and the severity of delayed-type
      hypersensitivity.
AB  - An altered balance between Th1 and Th2 cytokines is responsible for a variety of
      immunoinflammatory disorders such as asthma, yet the role of posttranscriptional
      mechanisms, such as those mediated by microRNAs (miRs), in adjusting the relative
      magnitude and balance of Th cytokine expression have been largely unexplored. In
      this study, we show that miR-21 has a central role in setting a balance between
      Th1 and Th2 responses to Ags. Targeted ablation of miR-21 in mice led to reduced
      lung eosinophilia after allergen challenge, with a broadly reprogrammed
      immunoactivation transcriptome and significantly increased levels of the Th1
      cytokine IFN-gamma. Biological network-based transcriptome analysis of OVA
      challenged miR-21(-/-) mice identified an unexpected prominent dysregulation of
      IL-12/IFN-gamma pathways as the most significantly affected in the lungs, with a
      key role for miR-21 in IFN-gamma signaling and T cell polarization, consistent
      with a functional miR-21 binding site in IL-12p35. In support of these
      hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS
      stimulation and OVA-challenged CD4(+) T lymphocytes to produce increased IFN
      gamma and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1
      associated delayed-type hypersensitivity cutaneous responses. Thus, our results
      define miR-21 as a major regulator of Th1 versus Th2 responses, defining a new
      mechanism for regulating polarized immunoinflammatory responses.

PMID- 21849677
TI  - IL-10 restricts activation-induced death of NK cells during acute murine
      cytomegalovirus infection.
AB  - IL-10 is an immunomodulatory cytokine that acts to antagonize T cell responses
      elicited during acute and chronic infections. Thus, the IL-10R signaling pathway
      provides a potential therapeutic target in strategies aimed at combating
      infectious diseases. In this study, we set out to investigate whether IL-10
      expression had an effect on NK cells. Murine CMV infection provides the best
      characterized in vivo system to evaluate the NK cell response, with NK cells
      being critical in the early control of acute infection. Blockade of IL-10R during
      acute murine CMV infection markedly reduced the accumulation of cytotoxic NK
      cells in the spleen and lung, a phenotype associated with a transient elevation
      of virus DNA load. Impaired NK cell responsiveness after IL-10R blockade was
      attributed to elevated levels of apoptosis observed in NK cells exhibiting an
      activated phenotype. Therefore, we conclude that IL-10 contributes to antiviral
      innate immunity during acute infection by restricting activation-induced death in
      NK cells.

PMID- 21849678
TI  - Ubiquitination of CD86 is a key mechanism in regulating antigen presentation by
      dendritic cells.
AB  - Dendritic cells (DCs) require costimulatory molecules such as CD86 to efficiently
      activate T cells for the induction of adaptive immunity. DCs maintain minimal
      levels of CD86 expression at rest, but upregulate levels upon LPS stimulation.
      LPS-stimulated DCs produce the immune suppressive cytokine IL-10 that acts in an
      autocrine manner to regulate CD86 levels. Interestingly, the underlying molecular
      mechanism behind the tight control of CD86 is not completely understood. In this
      study, we report that CD86 is ubiquitinated in DCs via MARCH1 E3 ubiquitin ligase
      and that this ubiquitination plays a key role in CD86 regulation. Ubiquitination
      at lysine 267 played the most critical role for this regulation. CD86 is
      ubiquitinated in MARCH1-deficient DCs to a much lesser degree than in wild-type
      DCs, which also correlated with a significant increase in CD86 expression.
      Importantly, CD86 is continuously ubiquitinated in DCs following activation by
      LPS, and this was due to the autocrine IL-10 inhibition of MARCH1 downregulation.
      Accordingly, DCs lacking MARCH1 and DCs expressing ubiquitination-resistant
      mutant CD86 both failed to regulate CD86 in response to autocrine IL-10. DCs
      expressing ubiquitination-resistant mutant CD86 failed to control their T cell
      activating abilities at rest as well as in response to autocrine IL-10. These
      studies suggest that ubiquitination serves as an important mechanism by which DCs
      control CD86 expression and regulate their Ag-presenting functions.

PMID- 21849679
TI  - Membrane-associated CD93 regulates leukocyte migration and C1q-hemolytic activity
      during murine peritonitis.
AB  - CD93 is emerging as a novel regulator of inflammation; however, its molecular
      function is unknown. CD93 exists as a membrane-associated glycoprotein on the
      surface of cells involved in the inflammatory cascade, including endothelial and
      myeloid cells. A soluble form (sCD93) is detectable in blood and is elevated with
      inflammation. In this study, we demonstrate heightened susceptibility to
      thioglycollate-induced peritonitis in CD93(-/-) mice. CD93(-/-) mice showed a 1.6
      1.8-fold increase in leukocyte infiltration during thioglycollate-induced
      peritonitis between 3 and 24 h that returned to wild type levels by 96 h.
      Impaired vascular integrity in CD93(-/-) mice during peritonitis was demonstrated
      using fluorescence multiphoton intravital microscopy; however, no differences in
      cytokine or chemokine levels were detected with Luminex Multiplex or ELISA
      analysis. C1q-hemolytic activity in CD93(-/-) mice was decreased by 22% at time
      zero and by 46% 3 h after thioglycollate injection, suggesting a defect in the
      classical complement pathway. Leukocyte recruitment and C1q-hemolytic activity
      was restored to wild type levels when CD93 was expressed on either hematopoietic
      cells or nonhematopoietic cells in bone marrow chimeric mice. However, elevated
      levels of sCD93 in inflammatory fluid were observed only when CD93 was expressed
      on nonhematopoietic cells. Because cell-associated CD93 was sufficient to restore
      a normal inflammatory response, these data suggest that cell-associated CD93, and
      not sCD93, regulates leukocyte recruitment and complement activation during
      murine peritonitis.

PMID- 21849680
TI  - Hierarchical IL-5 expression defines a subpopulation of highly differentiated
      human Th2 cells.
AB  - Each of the three Th2 cytokine genes, IL-4, IL-5, and IL-13, has different
      functions. We hypothesized that Th2 heterogeneity could yield Th2 subpopulations
      with different cytokine expression and effector functions. Using multiple
      approaches, we demonstrate that human Th2 cells are composed of two major
      subpopulations: a minority IL-5(+) (IL-5(+), IL-4(+), IL-13(+)) and majority IL
      5(-) Th2 (IL-5(-), IL-4(+), IL-13(+)) population. IL-5(+) Th2 cells comprised
      only 20% of all Th2 cells. Serial rounds of in vitro differentiation initially
      yielded IL-5(-) Th2, but required multiple rounds of differentiation to generate
      IL-5(+) Th2 cells. IL-5(+) Th2 cells expressed less CD27 and greater programmed
      cell death-1 than IL-5(-) Th2 cells, consistent with their being more highly
      differentiated, Ag-exposed memory cells. IL-5(+) Th2 cells expressed greater IL
      4, IL-13, and GATA-3 relative to IL-5(-) Th2 cells. GATA-3 and H3K4me(3) binding
      to the IL5 promoter (IL5p) was greater in IL-5(+) relative to IL-5(-) Th2 cells,
      whereas there was no difference in their binding to the IL4p and IL13p.
      Conversely, H3K27me(3) binding to the IL5p was greater in IL-5(-) Th2 cells.
      These findings demonstrate Th2 lineage heterogeneity, in which the IL5 gene is
      regulated in a hierarchical manner relative to other Th2 genes. IL-5(+) Th2 cells
      are phenotypically distinct and have epigenetic changes consistent with greater
      IL5p accessibility. Recurrent antigenic exposure preferentially drives the
      differentiation of IL-5(+) Th2 cells. These results demonstrate that IL-5(+) and
      IL-5(-) Th2 cells, respectively, represent more and less highly differentiated
      Th2 cell subpopulations. Such Th2 subpopulations may differentially contribute to
      Th2-driven pathology.

PMID- 21849681
TI  - Cutting edge: Crohn's disease-associated Nod2 mutation limits production of
      proinflammatory cytokines to protect the host from Enterococcus faecalis-induced
      lethality.
AB  - Nucleotide-binding oligomerization domain 2 (Nod2) mutations including
      L1007fsinsC are associated with the development of Crohn's disease (CD). These CD
      associated Nod2 mutations are common in healthy white populations, suggesting
      that they may confer some protective function, but experimental evidence is
      lacking. Using a mouse strain that expresses Nod2(2939iCstop), the equivalent of
      the L1007fsinsC mutation, we found that macrophages homozygous for
      Nod2(2939iCstop) are impaired in the recognition of muramyl dipeptide and
      Enterococcus faecalis, a commensal bacterium that is a common cause of sepsis
      associated lethality in humans. Notably, Nod2 deficiency and homozygocity for
      Nod2(2939iCstop) were associated with reduced production of TNF-alpha and IL-6
      and lethality after systemic infection with E. faecalis despite normal bacteria
      loads. Consistently, inhibition of TNF-alpha signaling protected wild-type mice
      from E. faecalis-induced lethality. These results suggest that the same Nod2
      mutation can increase the susceptibility to CD, but also protect the host from
      systemic infection by a common enteric bacterium.

PMID- 21849682
TI  - Activated protein C attenuates systemic lupus erythematosus and lupus nephritis
      in MRL-Fas(lpr) mice.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease leading to
      inflammatory tissue damage in multiple organs (e.g., lupus nephritis). Current
      treatments including steroids, antimalarials, and immunosuppressive drugs have
      significant side effects. Activated protein C is a natural protein with
      anticoagulant and immunomodulatory effects, and its recombinant version has been
      approved by the U.S. Food and Drug Administration to treat severe sepsis. Given
      the similarities between overshooting immune activation in sepsis and
      autoimmunity, we hypothesized that recombinant activated protein C would also
      suppress SLE and lupus nephritis. To test this concept, autoimmune female MRL
      Fas(lpr) mice were injected with either vehicle or recombinant human activated
      protein C from week 14-18 of age. Activated protein C treatment significantly
      suppressed lupus nephritis as evidenced by decrease in activity index, glomerular
      IgG and complement C3 deposits, macrophage counts, as well as intrarenal IL-12
      expression. Further, activated protein C attenuated cutaneous lupus and lung
      disease as compared with vehicle-treated MRL-Fas(lpr) mice. In addition,
      parameters of systemic autoimmunity, such as plasma cytokine levels of IL-12p40,
      IL-6, and CCL2/MCP-1, and numbers of B cells and plasma cells in spleen were
      suppressed by activated protein C. The latter was associated with lower total
      plasma IgM and IgG levels as well as lower titers of anti-dsDNA IgG and
      rheumatoid factor. Together, recombinant activated protein C suppresses the
      abnormal systemic immune activation in SLE of MRL-Fas(lpr) mice, which prevents
      subsequent kidney, lung, and skin disease. These results implicate that
      recombinant activated protein C might be useful for the treatment of human SLE.

PMID- 21849683
TI  - Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2
      restriction.
AB  - Regulatory T cells (Treg) are key players in maintaining immune homeostasis but
      have also been shown to regulate immune responses against infectious pathogens.
      Therefore, Treg are a promising target for modulating immune responses to
      vaccines to improve their efficacy. Using a viral vector system, we found that
      Treg act on the developing immune response early postinfection by reducing the
      extent of dendritic cell costimulatory molecule expression. Due to this change
      and the lower IL-2 production that results, a substantial fraction of CD8(+)
      effector T cells lose CD25 expression several days after activation.
      Surprisingly, such Treg-dependent limitations in IL-2 signaling by Ag-activated
      CD8(+) T cells prevent effector differentiation without interfering with memory
      cell formation. In this way, Treg fine-tune the numbers of effector T cells
      generated while preserving the capacity for a rapid recall response upon pathogen
      re-exposure. This selective effect of Treg on a subpopulation of CD8(+) T cells
      indicates that although manipulation of the Treg compartment might not be optimal
      for prophylactic vaccinations, it can be potentially exploited to optimize
      vaccine efficacy for therapeutic interventions.

PMID- 21849684
TI  - The facultative intracellular pathogen Candida glabrata subverts macrophage
      cytokine production and phagolysosome maturation.
AB  - Although Candida glabrata is an important human pathogenic yeast, its
      pathogenicity mechanisms are largely unknown. Immune evasion strategies seem to
      play key roles during infection, since very little inflammation is observed in
      mouse models. Furthermore, C. glabrata multiplies intracellularly after
      engulfment by macrophages. In this study, we sought to identify the strategies
      that enable C. glabrata to survive phagosome biogenesis and antimicrobial
      activities within human monocyte-derived macrophages. We show that, despite
      significant intracellular proliferation, macrophage damage or apoptosis was not
      apparent, and production of reactive oxygen species was inhibited. Additionally,
      with the exception of GM-CSF, levels of pro- and anti-inflammatory cytokines were
      only marginally increased. We demonstrate that adhesion to and internalization by
      macrophages occur within minutes, and recruitment of endosomal early endosomal Ag
      1 and lysosomal-associated membrane protein 1 indicates phagosome maturation.
      However, phagosomes containing viable C. glabrata, but not heat-killed yeasts,
      failed to recruit cathepsin D and were only weakly acidified. This inhibition of
      acidification did not require fungal viability, but it had a heat-sensitive
      surface attribute. Therefore, C. glabrata modifies the phagosome into a
      nonacidified environment and multiplies until the host cells finally lyse and
      release the fungi. Our results suggest persistence of C. glabrata within
      macrophages as a possible immune evasion strategy.

PMID- 21849685
TI  - The CD6 multiple sclerosis susceptibility allele is associated with alterations
      in CD4+ T cell proliferation.
AB  - Genome-wide association studies have revealed a large number of genetic
      associations with autoimmune diseases. Despite this progress, the mechanisms
      underlying the contribution of allelic variants to the onset of immune-related
      diseases remain mostly unknown. Our recent meta-analysis of genome-wide
      association studies of multiple sclerosis (MS) identified a new susceptibility
      locus tagged by a single nucleotide polymorphism, rs17824933 (p = 3.8 * 10(-9)),
      that is found in a block of linkage disequilibrium containing the CD6 gene.
      Because CD6 plays an important role in maintenance of T cell activation and
      proliferation, we examined the biologic phenotypes of the risk-associated allele.
      In this article, we report that the MS susceptibility allele in CD6 is associated
      with decreased expression of full-length CD6 in CD4(+) and CD8(+) T cells. As a
      consequence, proliferation is diminished during long-term activation of CD4(+) T
      cells from subjects with the risk allele. Selective knockdown of full-length CD6
      using exon 5-specific small interfering RNA induces a similar proliferation
      defect of CD4(+) T cells from subjects homozygous for the protective allele. Exon
      5 encodes for the extracellular binding site of the CD6 ligand ALCAM, which is
      required for CD6 stimulation. In CD4(+) T cells from subjects with the risk
      allele, exon 5 is consistently underexpressed, thereby providing a mechanism by
      which the allele affects proliferation of CD4(+) T cells. These findings indicate
      that the MS risk allele in the CD6 locus is associated with altered proliferation
      of CD4(+) T cells and demonstrate the influence of a disease-related allelic
      variant on important immunological characteristics.

PMID- 21849686
TI  - Achromobacter xylosoxidans: characterization of strains in Brazilian cystic
      fibrosis patients.
AB  - We investigated the possibility of cross-infection among cystic fibrosis patients
      in two Brazilian reference centers. Achromobacter xylosoxidans isolates (n = 122)
      were recovered over a 5-year period from 39 patients. Isolates were genetically
      heterogeneous, but one genotype was present in 56% of the patients, suggesting
      that cross-infection may have occurred.

PMID- 21849687
TI  - Gestational and fetal outcomes in B19 maternal infection: a problem of diagnosis.
AB  - Parvovirus B19 infection during pregnancy is a potential hazard to the fetus
      because of the virus' ability to infect fetal erythroid precursor cells and fetal
      tissues. Fetal complications range from transitory fetal anemia and nonimmune
      fetal hydrops to miscarriage and intrauterine fetal death. In the present study,
      72 pregnancies complicated by parvovirus B19 infection were followed up: fetal
      and neonatal specimens were investigated by serological and/or virological assays
      to detect fetal/congenital infection, and fetuses and neonates were clinically
      evaluated to monitor pregnancy outcomes following maternal infection. Analysis of
      serological and virological maternal B19 markers of infection demonstrated that
      neither B19 IgM nor B19 DNA detected all maternal infections. IgM serology
      correctly diagnosed 94.1% of the B19 infections, while DNA testing correctly
      diagnosed 96.3%. The maximum sensitivity was achieved with the combined detection
      of both parameters. B19 vertical transmission was observed in 39% of the
      pregnancies, with an overall 10.2% rate of fetal deaths. The highest rates of
      congenital infections and B19-related fatal outcomes were observed when maternal
      infections occurred by the gestational week 20. B19 fetal hydrops occurred in
      11.9% of the fetuses, and 28.6% resolved the hydrops with a normal
      neurodevelopment outcome at 1- to 5-year follow-up. In conclusion, maternal
      screening based on the concurrent analysis of B19 IgM and DNA should be
      encouraged to reliably diagnose maternal B19 infection and correctly manage
      pregnancies at risk.

PMID- 21849688
TI  - Sequence homologies between Mycoplasma and Chlamydia spp. lead to false-positive
      results in chlamydial cell cultures tested for mycoplasma contamination with a
      commercial PCR assay.
AB  - Mycoplasma contamination is a frequent problem in chlamydial cell culture. After
      obtaining contradictory contamination results, we compared three commercial PCR
      kits for mycoplasma detection. One kit signaled contamination in mycoplasma-free
      Chlamydia pneumoniae cultures. Sequencing of cloned PCR products revealed primer
      homology with the chlamydial genome as the basis of this false-positive result.

PMID- 21849689
TI  - Cerebral schistosomiasis due to Schistosoma haematobium confirmed by PCR analysis
      of brain specimen.
AB  - The case of a 25-year-old Japanese male who had cerebral schistosomiasis caused
      by Schistosoma haematobium is reported here. Although serum antibody tests showed
      a cross-reaction with other helminths and no ova were excreted in urine or feces,
      the existence of Schistosoma haematobium in the brain was confirmed by PCR
      analysis.

PMID- 21849690
TI  - Direct fluorescent-antibody testing followed by culture for diagnosis of 2009
      H1N1 influenza A.
AB  - During the 2009 H1N1 influenza A outbreak, 773 children were tested for influenza
      by direct fluorescent-antibody testing with PCR confirmation. Direct fluorescent
      antibody testing has a specificity of 99.6% but a sensitivity of only 65.0%.
      Physicians should recognize diagnostic limitations of direct fluorescent-antibody
      testing, which missed one-third of infected individuals.

PMID- 21849691
TI  - Extended multilocus variable-number tandem-repeat analysis of Clostridium
      difficile correlates exactly with ribotyping and enables identification of
      hospital transmission.
AB  - PCR ribotyping is currently used in many countries for epidemiological
      investigation to track transmission and to identify emerging variants of
      Clostridium difficile. Although PCR ribotyping differentiates over 300 types, it
      is not always sufficiently discriminatory for epidemiological investigations
      particularly for common ribotypes, e.g., ribotypes 027, 106, and 017. Multilocus
      variable-number tandem-repeat analysis (MLVA) is a highly discriminatory
      molecular subtyping method that has been applied to a number of bacterial species
      for high-level subtyping. Two MLVA typing schemes for C. difficile have been
      previously published, each utilizing seven variable-number tandem-repeat (VNTR)
      loci on the genome with four loci common to both schemes. Although these schemes
      are good genotyping methods with the ability to discriminate between isolates,
      they do not identify the ribotype. We show here that increasing the number of
      VNTR loci to 15, creating the extended MLVA (eMLVA) scheme, we have successfully
      subtyped all clinically significant ribotypes while still clustering isolates in
      concordance with PCR ribotyping. The eMLVA scheme developed here provides insight
      into the genetic diversity of the C. difficile population at both global and
      cross-infection clusters in patient levels, with the possibility of replacing PCR
      ribotyping.

PMID- 21849692
TI  - Inadequacies of minimum spanning trees in molecular epidemiology.
AB  - Minimum spanning trees (MSTs) are frequently used in molecular epidemiology
      research to estimate relationships among individual strains or isolates.
      Nevertheless, there are significant caveats to MST algorithms that have been
      largely ignored in molecular epidemiology studies and that have the potential to
      confound or alter the interpretation of the results of those analyses.
      Specifically, (i) presenting a single, arbitrarily selected MST illustrates only
      one of potentially many equally optimal solutions, and (ii) statistical metrics
      are not used to assess the credibility of MST estimations. Here, we survey
      published MSTs previously used to infer microbial population structure in order
      to determine the effect of these factors. We propose a technique to estimate the
      number of alternative MSTs for a data set and find that multiple MSTs exist for
      each case in our survey. By implementing a bootstrapping metric to evaluate the
      reliability of alternative MST solutions, we discover that they encompass a wide
      range of credibility values. On the basis of these observations, we conclude that
      current approaches to studying population structure using MSTs are inadequate. We
      instead propose a systematic approach to MST estimation that bases analyses on
      the optimal computation of an input distance matrix, provides information about
      the number and configurations of alternative MSTs, and allows identification of
      the most credible MST or MSTs by using a bootstrapping metric. It is our hope
      this algorithm will become the new "gold standard" approach for analyzing MSTs
      for molecular epidemiology so that this generally useful computational approach
      can be used informatively and to its full potential.

PMID- 21849693
TI  - CASA chromogenic medium for enteric Campylobacter species.
AB  - We prospectively assessed stool samples from 370 patients for Campylobacter
      species by comparing three selective agar media incubated at two temperatures: 42
      degrees C and 37 degrees C. Twenty patients (5.4%) were found positive. The
      chromogenic medium CASA (AES Chemunex, France) proved highly efficient for C.
      jejuni and C. coli recovery, while lessening the workload in the lab.

PMID- 21849694
TI  - Computational analysis of two species C human adenoviruses provides evidence of a
      novel virus.
AB  - Human adenovirus C (HAdV-C) species are a common cause of respiratory infections
      and can occasionally produce severe clinical manifestations. A deeper
      understanding of the variation and evolution in species HAdV-C is especially
      important since these viruses, including HAdV-C6, are used as gene delivery
      vectors for human gene therapy and in other biotechnological applications. Here,
      the full-genome analysis of the prototype HAdV-C6 and a recently identified virus
      provisionally termed HAdV-C57 are reported. Although the genomes of all species
      HAdV-C members are very similar to each other, the E3 region, hexon and fiber
      (ten proteins total) present a wide range of identity values at the amino acid
      level. Studies of these viruses in comparison to the other three HAdV-C
      prototypes (1, 2, and 5) comprise a comprehensive analysis of the diversity and
      conservation within HAdV-C species. HAdV-C6 contains a recombination event within
      the constant region of the hexon gene. HAdV-C57 is a recombinant virus with a
      fiber gene nearly identical to HAdV-C6 and a unique hexon distinguished by its
      loop 2 motif.

PMID- 21849695
TI  - Performance of Xpert MTB/RIF RUO assay and IS6110 real-time PCR for Mycobacterium
      tuberculosis detection in clinical samples.
AB  - The Cepheid Xpert MTB/RIF research-use-only (RUO) assay and a laboratory
      developed test (LDT) targeting IS6110 were evaluated and compared to
      mycobacterial culture as the gold standard. The performance characteristics of
      both molecular assays were determined by using 112 specimens from 90 patients,
      including 89 pulmonary specimens and 23 extrapulmonary specimens. Of the
      specimens tested, 37 (33%) were culture positive for the Mycobacterium
      tuberculosis complex; 29 were pulmonary, and 8 were extrapulmonary. Of these
      culture-positive specimens, 83% of the pulmonary specimens and 50% of the
      extrapulmonary specimens were smear positive. There was complete concordance
      between the smear-positive culture-positive specimens, independent of the
      anatomical site (100% sensitivity). The sensitivity of the MTB/RIF RUO assay for
      smear-negative specimens was 60% for pulmonary and 75% for extrapulmonary
      specimens, while the IS6110 LDT sensitivities were 40% and 0%, respectively.
      There was also complete concordance among the culture-negative specimens tested.
      Both assays showed 95% specificity, with four culture-negative specimens testing
      as positive. A review of patient records indicated that there was a high
      likelihood of the presence of M. tuberculosis complex DNA in the false-positive
      specimens. Biosafety analysis was performed and showed an acceptable reduction in
      organism viability using the processing methods described above. Both molecular
      assays are suitable for the detection of M. tuberculosis isolates in smear
      positive pulmonary and extrapulmonary specimens, while the sensitivity of the
      detection of M. tuberculosis isolates in smear-negative specimens was variable.

PMID- 21849696
TI  - Analysis of performance of a PCR-based assay to detect DNA of Aspergillus
      fumigatus in whole blood and serum: a comparative study with clinical samples.
AB  - The performance of a real-time PCR-based assay was retrospectively analyzed
      (according to European Organization for Research and Treatment of Cancer/Mycosis
      Study Group criteria) in the samples of patients with invasive aspergillosis. A
      total of 711 serial samples (356 whole-blood and 355 serum samples) from 38 adult
      patients were analyzed. The Aspergillus fumigatus PCR assay results were positive
      for 89 of 356 (25%) whole-blood samples and 90 of 355 (25.35%) serum samples.
      Positive PCR results were seen in 29 of 31 (93.5%) patients for which serum was
      analyzed and in 31 of 33 (93.9%) cases with whole-blood specimens. Both blood and
      serum samples were available in 26 cases, and significant differences were not
      observed in this subgroup of cases. The average number of threshold cycles (C(T))
      for positive blood samples was 37.6, and the average C(T) for serum was 37.4. The
      DNA concentration ranged between 2 and 50 fg per MUl of sample, with average DNA
      concentrations of 10.2 and 11.7 fg in positive blood and serum samples,
      respectively (P > 0.01). The performance of this PCR-based quantitative assay was
      similar for both serum and blood samples. We recommend serum samples as the most
      convenient hematological sample to use for Aspergillus DNA quantification when
      serial determinations are done.

PMID- 21849697
TI  - Presumptive identification of Clostridium difficile strain 027/NAP1/BI on Cepheid
      Xpert: interpret with caution.

PMID- 21849698
TI  - MicroRNA 21 "shapes" vascular smooth muscle behavior through regulating
      tropomyosin 1.

PMID- 21849699
TI  - Eicosapentaenoic acid and regression of atherosclerotic lesions: a role for
      dendritic cells.

PMID- 21849700
TI  - The complex metabolic mechanisms relating obesity to hypertriglyceridemia.

PMID- 21849701
TI  - Intelligent platelet inhibitors are on the horizon.

PMID- 21849702
TI  - Phosphate and CVD: it's all in what's on the table.

PMID- 21849703
TI  - Obesity and inflammatory vasculopathy: a surgical solution as ultima ratio?

PMID- 21849704
TI  - Beyond phosphorylation: nuclear export in vascular remodeling.

PMID- 21849705
TI  - Development of apolipoprotein E-deficient mice.

PMID- 21849706
TI  - Avian SERPINB11 gene: characteristics, tissue-specific expression, and regulation
      of expression by estrogen.
AB  - Serpins, a group of proteins with similar structural and functional properties,
      were first identified based on their unique mechanism of action: their inhibition
      of proteases. While most serpins have inhibitory roles, certain serpins are not
      involved in canonical proteolytic cascades but perform diverse functions
      including storage of ovalbumin in egg white, transport of hormones (thyroxine-
      and cortisol-binding globulin), and suppression of tumors. Of these, serpin
      peptidase inhibitor, clade B, member 11 (SERPINB11) is not an inhibitor of known
      proteases in humans and mice, and its function is unknown. In the present study,
      the SERPINB11 gene was cloned, and its expression profile was analyzed in various
      tissues from chickens. The chicken SERPINB11 gene has an open reading frame of
      1346 nucleotides that encode a protein of 388 amino acids that has moderate
      homology (38.8%-42.3%) to mammalian SERPINB11 proteins. Importantly, SERPINB11
      mRNA is most abundant in the chicken oviduct, specifically luminal and glandular
      epithelia, but it was not detected in any other chicken tissues of either sex. We
      then determined effects of diethylstilbestrol (DES; a synthetic nonsteroidal
      estrogen) on SERPINB11 expression in the chicken oviduct. Treatment of young
      chicks with DES induced SERPINB11 mRNA and protein only in luminal and glandular
      epithelial cells of the oviduct. Collectively, these results indicate that the
      novel estrogen-induced SERPINB11 gene is expressed only in epithelial cells of
      the chicken oviduct and implicate SERPINB11 in regulation of oviduct development
      and differentiated functions.

PMID- 21849707
TI  - Defining the impact of estrogen on spermatogonial fate.

PMID- 21849708
TI  - Role of angiotensin II in the periovulatory epidermal growth factor-like cascade
      in bovine granulosa cells in vitro.
AB  - Angiotensin II (AGT-2) induces follicular prostaglandin release in a number of
      species and ovulation in rabbits. Conversely, AGT-2 antagonists block ovulation
      in cattle. To determine the mechanism of action of AGT-2, we used a bovine
      granulosa cell model in which luteinizing hormone (LH) increased the expression
      of genes essential for ovulation in a time- and dose-dependent manner. The
      addition of AGT-2 to LH-stimulated cells significantly increased abundance of
      prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA and protein, whereas AGT-2
      alone had no effect. Upstream of PTGS2, AGT-2 increased abundance of mRNA
      encoding the epidermal growth factor-like ligands amphiregulin (AREG) and
      epiregulin (EREG) at 6 h posttreatment and abundance of a disintegrin and
      metalloprotease 17 (ADAM17), a sheddase, within 3 h of treatment. Inhibiting
      sheddase activity abolished the stimulatory effect of AGT-2 on AREG, EREG, and
      PTGS2 mRNA. The addition of selective AGT-2 antagonists to cells stimulated with
      LH plus AGT-2 demonstrated that AGT-2 did not act through the type 1 receptor and
      did not increase mitogen-activated protein kinase 3/1 phosphorylation. Combined
      with previous data from studies in vitro, we conclude that AGT-2 is an essential
      cofactor for LH in the early increase of ADAM expression/activity that induces
      the cascade of events leading to ovulation.

PMID- 21849709
TI  - [Erythemogenic UV rays].
AB  - The UV-index is an international standard measurement of the strength of
      erythemogenic ultraviolet radiation. It is often published in the media and then
      refers to the highest expected UV radiation for that day. The highest UV-index
      value measured in Iceland is seven. Although this is similar to the maximum
      values from southern Scandinavia, the average UV-index is lower in Iceland
      compared to other Nordic countries. Around solar noon the UV index is roughly
      equivalent to the Standard Erythema Dose (SED). During a bright summer day in
      Iceland the number of Standard Erythema doses can go as high as 32, but is on
      average in June around twenty. The typical Icelander gets red after 4-6 SED and
      it is obvious that during solar noon it is easy to sunburn in Iceland if you stay
      outside without sun protection.

PMID- 21849710
TI  - [University of Iceland - on crossroads at it's centennial].

PMID- 21849711
TI  - [Clear skies in Iceland? ].

PMID- 21849712
TI  - [Shortened hospital stay for elective cesarean section after initiation of a fast
      track program and midwifery home-care].
AB  - OBJECTIVE: To audit whether hospital stay shortened without increasing
      readmissions after implementation of fast-track methodology for elective cesarean
      section and characterize what influences length of stay. METHODS: A fast-track
      program was initiated in November 2008, with a one year clinical audit and
      satisfaction survey. Discharge criteria were predefined and midwife home visits
      included if discharge was within 48 hours. Hospital stay by parity for women with
      elective section for singleton pregnancy between 1.11. 2008 - 31.10. 2009 (n=213,
      fast-track 182) was compared to 2003 (n=199) and 2007 (n=183). Readmissions and
      outpatient visits 2007 and 2008-9 were counted. Reasons for longer stay were
      recorded in fast-track, and body mass index. RESULT: Median hospital stay
      decreased significantly from 81 to 52 hours between 2007 and 2008-9. Readmissions
      were four in each period and outpatient visit rates similar. In 2008-9, 66% of
      all women were discharged within 48 hours. Women in the fast-track program were
      satisfied with early discharge. Hospital stay for parous women was shorter in
      2007 compared to 2003, but unchanged for nulliparas. Parity had a minimal
      influence on length of stay in 2008-9, although nulliparous women <= 25 years
      were more likely to stay >48 hours. Body mass index did not correlate with length
      of stay. Pain was rarely the reason for a longer stay in the fast-track program
      and 90% were satisfied with pain-medication after discharge. CONCLUSION: Most
      healthy women can be discharged early after singleton birth by elective cesarean,
      without increasing readmissions.

PMID- 21849713
TI  - [UV-index in Iceland during the summer of 2010].
AB  - OBJECTIVE: To measure erythemogenic UV radiation in Iceland. MATERIAL AND
      METHODS: Erythemogenic UV radiation was measured during the period from April
      through September 2010. We used a UV sensor that measures the Erythema Action
      Spectrum as has been defined by the Commission Internationale de l'Eclairage
      (CIE) as the standard representation of the average skin response to UVB and UVA.
      The sensor was located in Skorradalur, Iceland (64,533287N; -21,526338W; altitude
      63 m.). The location of the sensor was carefully chosen to ensure that it was
      never in the shade. RESULTS: The maximum UV-index measured was higher than three
      21 days in May, 26 days in June, 26 days in July and 23 days in August. The
      highest value recorded was 7,3 on June 18th, at 13:25. UV index was measured as 5
      or higher on 16 days in June. The highest erythema weighted daily dose was
      measured to 19,2 SED in April, 27,1 SED in May, 32,2 SED in June, 30 SED in July,
      23,5 SED in August and 11,6 SED in September. DISCUSSION: These are the first
      results from measurements of UV-index and standard erythema dose (SED) in
      Iceland. The data shows that on a sunny day the UV-index can be relatively high.
      When the standard erythema dose was considered, high values were obtained during
      the summer months, with values up to six times what can cause sunburn.

PMID- 21849714
TI  - Putting encyclopaedia knowledge into structural form: finite state transducers
      approach.
AB  - In biology and functional genomics in particular, understanding the dependence
      and interplay between different genome and ecological characteristics of
      organisms is a very challenging problem. There are some public databases which
      combine this kind of information, but there is still much more information about
      microbes and other organisms that reside in unstructured and semi-structured
      documents, such as encyclopaedias. In this paper we present a method for
      extracting information from semi-structured resources, such as encyclopaedias,
      based on finite state transducers, consisting of two clearly distinguished
      phases. The first phase strongly relies on the analysis of the document structure
      and it is used for locating records of data in the text. The second phase is
      based on the finite state transducers created for extracting the data, which can
      be modified so as to achieve the preferred efficiency and it is used for
      extracting the particular characteristic from the text. We show how the two phase
      method is applied to the text of the encyclopaedia "Systematic Bacteriology". A
      fully structured database with genotype and phenotype characteristics of
      organisms has been created from the encyclopaedia unstructured descriptions.

PMID- 21849715
TI  - Evidence of electronic phase arrest and glassy ferromagnetic behaviour in
      (Nd(0.4)Gd(0.3))Sr(0.3)MnO3 manganite: comparative study between bulk and
      nanometric samples.
AB  - The effect of the doping of rare earth Gd(3+) ions replacing Nd(3+) in
      Nd(0.7)Sr(0.3)MnO(3) is investigated in detail. Measurements of resistivity,
      magnetoresistance, magnetization, and linear and nonlinear ac magnetic
      susceptibility on chemically synthesized (Nd(0.7-x)Gd(x))Sr(0.3)MnO(3) show
      various interesting features with doping level x=0.3. A comparative study has
      been carried out between a bulk and a nanometric sample (grain size ~60 nm)
      synthesized from the same as a prepared powder to maintain an identical
      stoichiometry. The resistivity of the samples shows strong dependence on the
      magnetic field-temperature history. The magnetoresistance of the samples also
      shows strong irreversibility with respect to sweeping of the field between the
      highest positive and negative values. Moreover, the resistivity is found to
      increase with time after field cooling and then switching off the field. All
      these phenomena have been attributed to phase separation effects and the arrest
      of phases in the samples. Furthermore, the bulk sample displays a spin glass like
      behaviour as evident from the frequency dependence of linear ac magnetic
      susceptibility and critical divergence of the nonlinear ac magnetic
      susceptibility. The experimentally obtained characteristic time tau(0) after
      dynamical scaling analysis of the frequency dependence of the ac susceptibility
      is found to be 10(-17) s which implies that the system is different from a
      canonical spin glass. An unusual frequency dependence of the second harmonic of
      ac susceptibility around the magnetic transition temperature led us to designate
      the magnetic state of the sample to be glassy ferromagnetic. On reduction of the
      grain size low field magnetoresistance and phase arrest phenomena are found to
      enhance but the glassy state is observed to be destabilized in the nanometric
      sample.

PMID- 21849716
TI  - Carbon release by selective alloying of transition metal carbides.
AB  - We have performed first principles density functional theory calculations on TiC
      alloyed on the Ti sublattice with 3d transition metals ranging from Sc to Zn. The
      theory is accompanied by experimental investigations, both as regards materials
      synthesis as well as characterization. Our results show that by dissolving a
      metal with a weak ability to form carbides, the stability of the alloy is lowered
      and a driving force for the release of carbon from the carbide is created. During
      thin film growth of a metal carbide this effect will favour the formation of a
      nanocomposite with carbide grains in a carbon matrix. The choice of alloying
      element as well as its concentration will affect the relative amount of carbon in
      the carbide and in the carbon matrix. This can be used to design the structures
      of nanocomposites and their physical and chemical properties. One example of
      applications is as low-friction coatings. Of the materials studied, we suggest
      the late 3d transition metals as the most promising elements for this phenomenon,
      at least when alloying with TiC.

PMID- 21849717
TI  - Crossover from itinerant-electron to localized-electron behavior in Sr(1
      x)Ca(x)CrO3 perovskite solid solution.
AB  - Polycrystalline samples of the perovskite family Sr(1-x)Ca(x)CrO(3) have been
      prepared at high pressure and temperature in steps of 1/6 over the range 0 <= x
      <= 1. Rietveld analysis shows a series of structural phase transitions from cubic
      to tetragonal to orthorhombic with increasing x. The cubic samples have no long
      range magnetic order; the other samples become antiferromagnetically ordered
      below a T(N) that increases with x. At ambient pressure, the electric transport
      properties of the cubic and tetragonal phases are semiconducting with a small
      (meV range) activation energy that increases with x; the orthorhombic phase
      exhibits variable-range hopping rather than the small-polaron behavior typically
      found for mixed-valent, localized-electron configurations. Above a pressure
      P=P(C), a smooth insulator-metal transition is found at a T(IM) that decreases
      with increasing P for a fixed x; P(C) increases with x. These phenomena are
      rationalized qualitatively with a pi(*)-band model having a width W(pi) that
      approaches crossover from itinerant-electron to localized-electron behavior as
      W(pi) decreases with increasing x. The smaller size of the Ca(2+) ion induces the
      structural changes and the greater acidity of the Ca(2+) ion is primarily
      responsible for narrowing W(pi) as x increases.

PMID- 21849718
TI  - Multi-orbital non-crossing approximation from maximally localized Wannier
      functions: the Kondo signature of copper phthalocyanine on Ag(100).
AB  - We have developed a multi-orbital approach to compute the electronic structure of
      a quantum impurity using the non-crossing approximation. The calculation starts
      with a mean-field evaluation of the system's electronic structure using a
      standard quantum chemistry code; here we use density functional theory (DFT). We
      transformed the one-electron structure into an impurity Hamiltonian by using
      maximally localized Wannier functions. Hence, we have developed a method to study
      the Kondo effect in systems based on an initial one-electron calculation. We have
      applied our methodology to a copper phthalocyanine molecule chemisorbed on
      Ag(100), and we have described its spectral function for three different cases
      where the molecule presents a single spin or two spins with ferro- and anti
      ferromagnetic exchange couplings. We find that the use of broken-symmetry mean
      field theories such as Kohn-Sham DFT cannot deal with the complexity of the spin
      of open-shell molecules on metal surfaces and extra modeling is needed.

PMID- 21849719
TI  - The effect of skin thermistor fixation method on weighted mean skin temperature.
AB  - The purpose of this study was to investigate the effect of three different skin
      thermistor attachment methods on weighted mean skin temperature (WMT(sk)) at
      three different ambient temperatures (approximately 24  degrees C (TEMP);
      approximately 30  degrees C (WARM); approximately 35  degrees C (HOT)) compared
      to uncovered thermistors. Eleven, non-acclimated, volunteers completed three 5
      min bouts of submaximal cycling (approximately 70 W mechanical work)-one at each
      environmental condition in sequential order (TEMP, WARM, HOT). One thermistor was
      fixed to the sternal notch whilst four skin thermistors were spaced at 3 cm
      intervals on each of the sites on the limbs as per the formula of Ramanathan
      (1964 J. Appl. Physiol. 19 531-3). Each thermistor was either held against the
      skin uncovered (UC) or attached with surgical acrylic film dressing (T); surgical
      acrylic film dressing and hypoallergenic surgical tape (TT) or surgical acrylic
      film dressing, hypoallergenic surgical tape and surgical bandage (TTC). The
      WMT(sk) calculated was significantly lower in UC compared to T, TT and TTC (p <
      0.001, d = 0.46), in T compared to TT and TTC (p < 0.001, d = 0.33) and in TT
      compared to TTC (p < 0.001; d = 0.25). The mean differences (across the three
      temperatures) were + 0.27 +/- 0.34  degrees C, + 0.52 +/- 0.35  degrees C and +
      0.82 +/- 0.34  degrees C for T, TT and TTC, respectively. The results demonstrate
      that the method of skin thermistor attachment can result in the significant over
      estimation of weighted mean skin temperature.

PMID- 21849720
TI  - Comparison of blood volume pulse and skin conductance responses to mental and
      affective stimuli at different anatomical sites.
AB  - Measurements of blood volume pulse (BVP) and skin conductance are commonly used
      as indications of psychological arousal in affective computing and human-machine
      interfaces. To date, palmar surfaces remain the primary site for these
      measurements. Placement of sensors on palmar surfaces, however, is undesirable
      when recordings are fraught with motion and pressure artifacts. These artifacts
      are frequent when the human participant has involuntary movements as in
      hyperkinetic cerebral palsy. This motivates the use of alternative measurement
      sites. The present study examined the correlation between measurements of blood
      volume pulse and skin conductance obtained from three different sites on the body
      (fingers, toes and ear for BVP; fingers, toes and arch of the foot for skin
      conductance) in response to cognitive and affective stimuli. The results of this
      pilot study indicated significant inter-site correlation among signal features
      derived from different sites, with the exception of BVP amplitude, the number of
      electrodermal reactions and the slope of the electrodermal activity response. We
      attribute these differences in part to inter-site discrepancies in local skin
      conditions, such as skin temperature. Despite these differences, significant
      changes from baseline were present in the responses to the cognitive and
      affective stimuli at non-palmar sites, suggesting that these sites may provide
      viable signal measurements for use in affective computing and human-machine
      interface applications.

PMID- 21849721
TI  - A continuous wavelet transform-based method for time-frequency analysis of
      artefact-corrected heart rate variability data.
AB  - Time-frequency analysis of heart rate variability (HRV) provides relevant
      clinical information. However, time-frequency analysis is very sensitive to
      artefacts. Artefacts that are present in heart rate recordings may be corrected,
      but this reduces the variability in the signal and therefore adversely affects
      the accuracy of calculated spectral estimates. To overcome this limitation of
      traditional techniques for time-frequency analysis, a new continuous wavelet
      transform (CWT)-based method was developed in which parts of the scalogram that
      have been affected by artefact correction are excluded from power calculations.
      The method was evaluated by simulating artefact correction on HRV data that were
      originally free of artefacts. Commonly used spectral HRV parameters were
      calculated by the developed method and by the short-time Fourier transform
      (STFT), which was used as a reference. Except for the powers in the very low
      frequency and low-frequency (LF) bands, powers calculated by the STFT proved to
      be extremely sensitive to artefact correction. The CWT-based calculations in the
      high-frequency and very high-frequency bands corresponded well with their
      theoretical values. The standard deviations of these powers, however, increase
      with the number of corrected artefacts which is the result of the non
      stationarity of the R-R interval series that were analysed. The powers calculated
      in the LF band turned out to be slightly sensitive to artefact correction, but
      the results were acceptable up to 20% artefact correction. Therefore, the CWT
      based method provides a valuable alternative for the analysis of HRV data that
      cannot be guaranteed to be free of artefacts.

PMID- 21849722
TI  - Elastomeric degradable biomaterials by photopolymerization-based CAD-CAM for
      vascular tissue engineering.
AB  - A predominant portion of mortalities in industrial countries can be attributed to
      diseases of the cardiovascular system. In the last decades great efforts have
      been undertaken to develop materials for artificial vascular constructs. However,
      bio-inert materials like ePTFE or PET fail as material for narrow blood vessel
      replacements (coronary bypasses). Therefore, we aim to design new biocompatible
      materials to overcome this. In this paper we investigate the use of
      photoelastomers for artificial vascular constructs since they may be precisely
      structured by means of additive manufacturing technologies. Hence, 3D computer
      aided design and manufacturing technologies (CAD-CAM) offer the possibility of
      creating cellular structures within the grafts that might favour ingrowth of
      tissue. Different monomer formulations were screened concerning their suitability
      for this application but all had drawbacks, especially concerning the suture tear
      resistance. Therefore, we chose to modify the original network architecture by
      including dithiol chain transfer agents which effectively co-react with the
      acrylates and reduce crosslink density. A commercial urethane diacrylate was
      chosen as base monomer. In combination with reactive diluents and dithiols, the
      properties of the photopolymers could be tailored and degradability could be
      introduced. The optimized photoelastomers were in good mechanical accordance with
      native blood vessels, showed good biocompatibility in in vitro tests, degraded
      similar to poly(lactic acid) and were successfully manufactured with the 3D CAD
      CAM technology.

PMID- 21849723
TI  - Targeting ligand-functionalized and redox-sensitive heparin-Pluronic nanogels for
      intracellular protein delivery.
AB  - The heparin-Pluronic (HP) conjugate was coupled via redox-sensitive disulfide
      bond and contains a vinyl sulfone (VS) group with high reactivity to some
      functional groups such as thiol group. Heparin was conjugated with cystamine and
      the terminal hydroxyl groups of Pluronic were activated with the VS group,
      followed by coupling of VS groups of Pluronic with cystamine of heparin. The
      chemical structure, heparin content and VS group content of the resulting product
      were determined by (1)H NMR, FT-IR, toluidine blue assay and Ellman's method. The
      HP conjugate formed a type of nanogel in an aqueous medium, showing a critical
      micelle concentration of approximately 129.35 mg L(-1), a spherical shape and the
      mean diameter of 115.7 nm, which were measured by AFM and DLS. The release test
      demonstrated that HP nanogel was rapidly degraded when treated with glutathione.
      Cytotoxicity results showed a higher viability of drug-free HP nanogel than that
      of drug-loaded one. Cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGDfC) peptide was efficiently
      conjugated to VS groups of HP nanogel and exhibited higher cellular uptake than
      unmodified nanogels. All results suggest a novel multi-functional nanocarrier
      delivery and effective release of proteins to the intracellular region in a redox
      sensitive manner.

PMID- 21849724
TI  - Effects of nonlinearity in the materials used for the semi-rigid pedicle screw
      systems on biomechanical behaviors of the lumbar spine after surgery.
AB  - Recently, various types of semi-rigid pedicle screw fixation systems have been
      developed for the surgical treatment of the lumbar spine. They were introduced to
      address the adverse issues commonly found in traditional rigid spinal fusion-
      abnormally large motion at the adjacent level and subsequent degeneration. The
      semi-rigid system uses more compliant materials (nitinol or polymers) and/or
      changes in rod design (coiled or twisted rods) as compared to the conventional
      rigid straight rods made of Ti alloys (E = 114 GPa, upsilon = 0.32). However,
      biomechanical studies on the semi-rigid pedicle screw systems were usually
      limited to linear modeling of the implant and anatomic elements, which may not be
      capable of reflecting realistic post-operative motions of the spine. In this
      study, we evaluated the effects of nonlinearity in materials used for semi-rigid
      pedicle screw fixation systems to evaluate the changes in biomechanical behaviors
      using finite element analysis. Changes in range of motion (ROM) and center of
      rotation (COR) were assessed at the operated and adjacent levels. Actual load
      displacement results of the semi-rigid rod from mechanical test were carried out
      to reflect the nonlinearity of the implant. In addition, nonlinear material
      properties of various spinal ligaments studies were used for the finite element
      modeling. The post-operative models were constructed by modifying the previously
      validated intact model of the L1-S1 spine. Eight different post-operative models
      were made to address the effects of nonlinearity-with a traditional stiffness
      modulus rod (with linear ligaments, case 1; with nonlinear ligaments, case 5),
      with a rigid rod (with linear ligaments, case 2; with nonlinear ligaments, case
      6), with a soft rod (with linear ligaments, case 3; with nonlinear ligaments,
      case 7), and with a nonlinear rod (with linear ligaments, case 4; with nonlinear
      ligaments, case 8). To simulate the load on the lumbar spine in a neutral
      posture, follower load (400 N) was applied and then the hybrid loading condition
      was applied to measure the ROM and COR in the sagittal plane. The more the
      nonlinearity was included in the model the closer the motion behavior of the
      device was to that of the intact spine. Furthermore, our results showed that the
      nonlinearity of the semi-rigid rod was a more sensitive factor than the
      nonlinearity of the spinal ligaments on biomechanical behavior of the lumbar
      spine after surgery. Therefore, for better understanding of the surgical
      effectiveness of the spinal device, more realistic material properties such as
      nonlinearity of the device and anatomic elements should be considered. In
      particular, the nonlinear properties of the semi-rigid rod were considered more
      than the nonlinearity of spinal ligaments.

PMID- 21849725
TI  - Is chronic opioid use a negative predictive factor for response to cervical
      epidural steroid injections?
AB  - BACKGROUND: Cervical epidural steroid injections (ESIs) are often used to treat
      patients with neck and upper extremity pain associated with a cervical
      radiculopathy. The effect of chronic opioid use in cervical radiculopathy
      patients managed with ESIs is unknown; past studies suggest that these patients
      may behave differently than opioid naive patients. The purpose of this study is
      to determine the effect of chronic (greater than 6 months) opioid use on the
      immediate outcome of cervical ESIs. METHODS: A two year retrospective chart
      review identified 22 consecutive patients with cervical radiculopathy who
      underwent a single level interlaminar cervical ESI, main outcome variable was >
      50% pain relief on VAS at follow up. Inclusion factors were unilateral disc
      protrusion, exclusion factors were severe central canal or foraminal stenosis,
      spondylolithesis, spinal instability, cord edema, or with multi-level disc
      protrusions. RESULTS: Using a linear logistic regression analysis on both patient
      demographics and physical exam measures, the most significant explanatory model
      was the use of opiates at the time of injection; 70% of opioid naive patients had
      a favorable outcome while only 20% of patients managed with chronic opioids had
      relief (p= 0.06). CONCLUSIONS: Patients managed with opioids chronically may
      respond in a different manner to ESIs when compared to opioid naive patients.

PMID- 21849726
TI  - A comparison of the thoracic spine in the sagittal plane between elite cyclists
      and non-athlete subjects.
AB  - AIM: to evaluate and compare the angular disposition of the thoracic spine (at
      different postures) in elite cyclists and a group of individuals who do not
      exercise in a systematic manner. METHODS: Sixty elite cyclists and sixty-eight
      sedentary individuals (control group), mean age: 21.91 (2.86) years participated
      in this study. Thoracic spine was measure with a Spinal Mouse(r) while relaxed
      standing, lying prone and sitting on the bicycle in three handlebar positions
      (upper, middle and lower handlebar). RESULTS: The mean (SEM) thoracic kyphosis
      while standing was 48.17 (8.05 degrees ) and 42.68 (8.02 degrees ) in cyclists
      and control group, respectively (p< 0.001). The thoracic curve adopted in lying
      prone was 34.69 (8.28 degrees ) in cyclists and 30.96 (7.24 degrees ) in control
      group (p< 0.05). On the bicycle, cyclists showed lower thoracic kyphosis with
      respect to control group (p> 0.05). The thoracic spine was adopted more neutral
      in the posture sitting on bicycle than in relaxed standing, in both groups
      analyzed. CONCLUSION: The posture adopted in cycling is not the only result of
      the higher thoracic curvature in cyclists when standing. It is necessary to
      include spinal postural awareness in the training plan and thoracic muscle
      resistance exercises that favour more aligned postures while standing.

PMID- 21849727
TI  - Medial superior cluneal nerve entrapment neuropathy in military personnel;
      diagnosis and etiologic factors.
AB  - BACKGROUND AND OBJECTIVES: Pain caused by medial superior cluneal nerve
      entrapment (MSCNE) is an infrequent cause of unilateral low back pain. There is
      limited information about this neuropathy in the literature. In this study, the
      etiologic factors leading to this clinical entity were evaluated and also the
      clinical and imaging findings were examined. MATERIAL AND METHOD: The study was
      conducted in 3 groups. The study group included 25 patients with MSCNE, the
      hernia group included 25 patients with herniated nucleosus pulposus and the
      control group included 25 healthy subjects. The initial evaluation included
      lumbar computerized tomography (CT) and magnetic resonance imaging (MRI) in the
      study and the hernia groups. The comparisons between these two groups were made
      by using clinical assessment questionnaires (SF-36 mental and physical health
      scores and Oswestry scale). Additionally, all three groups were compared by
      lumbosacral radiographies and low back superficial ultrasonographies. As
      treatment, 1 ml of prilocaine combined with 1 ml of steroid injection was used in
      the study group. RESULTS: In the study group, there was no disc herniation, facet
      joint problems, spinal stenosis or spondylolisthesis detected by CT or MRI. The
      SF-36 mental health score before treatment was lower in the study group than in
      the hernia group. The ultrasonographic examination detected a paravertebral
      hypoechogenic globular-shaped muscle disorganization associated with lipomatous
      degeneration exclusively localized to the trigger point in the study group. Both
      the mean soft tissue and the periiliac band thickness were significantly higher
      in the study group than in the other two groups. The lumbosacral radiographies
      did not show any significant difference in either the degree of lumbar spinal
      lordosis or the intercristal line levels among the three groups. CONCLUSION: This
      prospective study depicts the etiologic factors, ultrasonographic features and
      treatment protocol of MSCNE which is usually an underestimated cause of the low
      back pain. LEVEL OF EVIDENCE: Diagnostic study, Level I-1 (prospective study).

PMID- 21849728
TI  - Validity and reliability of the Greek version of the Quebec Back Pain Disability
      Scale.
AB  - OBJECTIVES: Low back pain is related to functional status and possible resulting
      disability. The Quebec Back Pain Disability Scale (QBPDS) has been used widely to
      evaluate functional disability in patients with low back pain. The purpose of
      this study was to assess: (a) the face and content validity, (b) the factor
      structure, (c) the concurrent validity, (d) the discriminant validity, (e) the
      internal consistency and the test-retest reliability (ICC) of the Greek version
      of the QBPDS. METHODS: One hundred and sixty patients with low back pain
      participated in the study. Face and content validity of the translated QBPDS were
      first investigated and afterwards exploratory factor analysis (EFA) was chosen to
      examine the factor structure of it. The concurrent and discriminant validity of
      the QBPDS was also assessed by a number of valid constructs. Finally, Cronbach
      alpha and Pearson r (ICC) were used to investigate the reliability of the
      instrument. RESULTS: The face and content validity of the QBPDS were supported
      and the EFA confirmed the sixth initial factor structure of the instrument. The
      concurrent and discriminant validity of it was confirmed by examining
      correlations between the QBPDS with other constructs. The Cronbach a and the ICCs
      indices of the instrument were acceptable. CONCLUSION: The Greek translation of
      the QBPDS provided reliable and valid instrument for the evaluation of Greek
      patients with low back pain.

PMID- 21849729
TI  - Effectiveness of diadynamic currents and transcutaneous electrical nerve
      stimulation in disc disease lumbar part of spine.
AB  - BACKGROUND: Back pain has multi-factorial etiology and is modified by
      environmental influences, character of work, and individual predispositions.
      OBJECTIVE: The aim of this study was to compare the efficiency of analgesic DD
      current therapy and TENS in low back discopathy. MATERIAL AND METHODS: Eighty
      patients (age, 45-60 years) with diagnosed low back pain syndrome due to
      discopathy were subjected to therapy. In the first group (DD) of 40 people, DD
      current therapy was applied. In the second group (TENS) of 40 people, TENS was
      applied. The third group of 40 people was a control group in which a functional
      fitness test was performed for comparison purposes. The control group was in this
      case an equivalent to a norm. Before the beginning and on the completion of
      therapy in all patients, a pain level measurement and functional fitness test
      were performed. RESULTS: On the basis of research conducted it was stated that
      both therapies reduce pain level effectively. Obtained analyzed results conclude
      that both therapies applied have an analgesic effect. CONCLUSIONS: DD current and
      TENS therapies in low back discopathy have an analgesic impact and improve
      functional fitness. The applied therapies have a comparable impact on researched
      parameters.

PMID- 21849730
TI  - Work status and health-related quality of life following multimodal work
      hardening: a cluster randomised trial.
AB  - BACKGROUND: Systematic reviews have confirmed the effectiveness of work-related
      rehabilitation with significant cognitive-behavioural components for patients
      with musculoskeletal disorders (MSDs). In Germany, however, work-related
      rehabilitation focuses mainly on functional capacity training and less on
      psychosocial work demands. OBJECTIVE: To evaluate the efficacy of multimodal work
      hardening (MWH) with a cognitive-behavioural approach. METHODS: Patients with
      MSDs resulting in severe restriction of work ability were randomly assigned to
      treatment by either MWH or conventional musculoskeletal rehabilitation
      (controls). The primary outcome was work status. The work status at 6 months of
      follow-up was defined as positive if the patient was working and had <= 6 weeks
      of sick leave, and that at 12 months was defined as positive if the patient was
      working and had <=12 weeks of sick leave. Follow-up data were collected by postal
      questionnaires. RESULTS: 236 patients consented to participate. Follow-up data
      were obtained from 169 (71.6%) participants at 6 months and 146 (61.9%)
      participants at 12 months. At 6 months, participants in the MWH group had a 2.4
      times higher chance of a positive work status than the controls (OR=2.363; 95%
      CI: 1.266 to 4.410; p=0.007). At 12 months, the chances of a positive work status
      were still higher, but this difference was not statistically significant
      (OR=1.914; 95% CI: 0.849 to 4.317; p=0.118). Significance of the interaction term
      of treatment and time indicated more favourable outcomes for depression and
      anxiety, mental and physical health-related quality of life, and pain management
      in the MWH group. CONCLUSIONS: MWH improves health-related quality of life and is
      able to enhance the mid-term chances of work-life participation.

PMID- 21849731
TI  - The effectiveness of scapular stabilization exercise in the patients with
      subacromial impingement syndrome.
AB  - OBJECTIVE: The study investigated the effectiveness of stretching, strengthening
      exercises, and the scapular stabilization exercises on the pain, shoulder range
      of motion (ROM), muscle strength, joint position sense (JPS), scapular dyskinesis
      and quality of life (OL) in the patients with subacromial impingement syndrome
      (SIS). METHODS: 27 women and 13 men, mean age 51 (24-71) years old, were included
      in this study. All the patients were separated into 2 groups according to simple
      random table. Stretching and strengthening exercises were given to the group I
      (n=20) and scapular stabilization exercises were added to the group II (n=20).
      The pain severity, shoulder ROM, muscle strength, JPS, lateral scapular slide
      test (LSST), Western Ontario Rotator Cuff (WORC) Index were evaluated before and
      after treatment. Patients completed a 6-week rehabilitation program, three times
      a week. RESULTS: The results showed that all measurements improved statistically
      in both groups after treatment (p < 0.05). And the improvements in the muscle
      strength, JPS and scapular dyskinesia were significantly different in group II (p
      < 0.05). CONCLUSION: It is suggested that in the treatment of SIS; scapular
      stabilization exercises, given with stretching and strengthening exercises, can
      be more effective in increasing the muscle strength, developing the JPS and
      decreasing the scapular dyskinesis.

PMID- 21849732
TI  - The effect of group-exercising on females with non-specific chronic low back pain
      in a sitting position: a pilot study.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of active group
      exercising on women with non specific chronic low back pain (NSCLBP) in a sitting
      position. METHODS: 25 females with NSCLBP underwent 8 group sitting-exercise
      sessions of a 45 minute duration, over an 8 week period. Pain intensity (VAS),
      back specific disability (Rolland Morris questionnaire-RMQ), and lumbar flexion
      and extension ranges of motion were measured twice, for reliability tests and cut
      off score values, with a 1 week interval between measurements, prior to
      intervention and subsequently, six weeks following intervention. RESULTS: Several
      significant changes in outcome measures were indicated following intervention
      compared with baseline (p < 0.001): an increase in lumbar flexion and extension
      (mean differences of 6 degrees  for flexion and 4 degrees  for extension, cutoff
      score = 5.91 degrees ); reduction in VAS score (mean difference=4.21, cutoff
      score =4.48); an increase in RMQ total score (mean difference=10.76, cutoff
      score=8.15). Changes in the VAS score was highly correlated with changes in the
      RMQ score (r=- 6.35). CONCLUSIONS: A functional program of group-exercising
      conducted in a sitting position, improved the functional, painful status and
      lumbar ranges of motion in the sagittal plane of women suffering from non
      specific chronic low back pain. As sitting is considered the most common posture
      in today's workplace, applying this protocol during working hours would be very
      effective.

PMID- 21849733
TI  - Evaluation of patients' response to pulsed radiofrequency treatment applied to
      the suprascapular nerve in patients with chronic shoulder pain.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate patient
      satisfaction, efficacy and safety of the pulsed radiofrequency (PRF) technique
      applied to the suprascapular nerve for the treatment of refractory shoulder pain.
      METHODS: After obtaining Institutional Research Board approval and patients'
      written informed consent, patients with chronic shoulder pain resistant to
      medical treatment were included in prospective study and PRF technique was
      applied to the suprascapular nerve for 480 seconds. Verbal Numerical Rating Scale
      (VNRS) at 0, 3, and 6 months post procedure and Modified MacNab score before and
      6 months after procedure are performed. Fifty percent or more decrease in VNRS
      and Modified MacNab score as Excellent and Good are accepted as a significant
      pain relief, 20 to 49% decrease is accepted as partial. Any complication related
      to procedure was also recorded. RESULTS: Fifty-seven patients were included in
      the study. PRF treatment significantly relieved at the pain in 73.7% patients [42
      patients out of 57]. Ten patients [17.5%] showed partial improvement and there
      were no changes at the pain scores in 5 patients [8.7%]. Forty-five patients
      [78.9%] showed improvement in VNRS scores as well as in Modified MacNab scores at
      6 months after treatment. No side effects were reported. Pain scores were given
      as mean +/- SD. Also, The Kaplan-Meier analysis was done for patients' shoulder
      pain after treatment with pulsed radiofrequency. CONCLUSION: Pulsed
      radiofrequency technique application to the suprascapular nerve for 480 seconds
      shows remarkable improvement at patients' chronic shoulder pain.

PMID- 21849734
TI  - Effects of continuous perfusion on human bone marrow stromal cells seeded on a
      decellularized bovine Achilles tendon matrix.
AB  - Ruptures of tendons and ligaments are a widely common injury in traumatology. The
      aim of the study was the development of a substitute tissue for such defects by
      methods of tissue-engineering. Human bone marrow stromal cells (hBMSC) were
      seeded on a decellularized bovine Achilles tendon and cultivated in a special
      bioreactor. We examined the influence of continuous perfusion on proliferation
      and biomechanical stability compared to static cultivation. Samples were taken on
      day 0, 7 and 14. Decellularized tendons were chosen as a negative control. Cell
      quantity was measured by the MTS-Test. Histology was analyzed by Haematoxylin
      Eosin- and Pentachrome-coulouring. The cultivated tendons were tested
      biomechanically compared with the decellularized control group. MTS-Test revealed
      an increase of cell count of 7% in the static group and a decrease of 9% in the
      perfusion group. The perfusion group showed a stronger network of the fibroblasts
      and a higher amount of produced extracellular matrix. Biomechanical testing
      revealed significantly higher stability in the decellularized control group. This
      trial shows up new possibilities of managing defects of tendons and ligaments.
      The continuous perfusion in a bioreactor can improve the structure of the matrix
      seeded with hBMSC.

PMID- 21849735
TI  - A pilot usability study of MINWii, a music therapy game for demented patients.
AB  - MINWii is a music therapy game for the renarcissization of demented patients. It
      lets players improvise or play songs of their choice by pointing at a virtual
      keyboard with a Wiimote Pistol. We present the results of a three-month usability
      study we conducted with 7 institutionalized patients suffering from mild to
      moderately severe Alzheimer's disease at the LUSAGE Living Lab in Paris. We
      demonstrate that MINWii is indeed usable by AD patients despite their motor and
      cognitive impairments: our results, which were largely computed automatically
      thanks to MINWii's extensive logging capabilities, show either an instant mastery
      or a clear learning effect depending on patients' cognitive abilities. Moreover,
      patients were overall very satisfied with the game and expressed a desire to
      repeat the experience: MINWii fosters positive interaction with the caregivers
      and elicits powerful reminiscence with even the most severely impaired patients.
      This study justifies future research to assess the lasting effects of playing
      MINWii on both quality of life and cognitive impairment in demented patients.

PMID- 21849736
TI  - Towards an assessment of bone fracture healing using pulsed mode ultrasound.
AB  - Healing rate of fractured bone differs from one patient to another which may lead
      to incorrect consequent medical procedures. Thus, quantitative assessment of bone
      healing after fracture becomes important. In this paper, we present a
      mathematical model which describes the interaction of a pulsed mode ultrasound
      waves with a multilayered biological structure. The model is applied to estimate
      the bone callus thickness and degree of hardness. Different frequencies are
      utilized to obtain highest measurement sensitivity and accuracy of callus
      thickness and degree of hardness. It is found that a transducer operating at 1
      MHz has the highest sensitivity to the different phases of callus hardening. On
      the other hand, a 3 MHz transducer yields the highest sensitivity to the
      thickness of the callus layer. Thus, using both frequencies might prove to be
      useful for full quantitative assessment of the bone healing process.

PMID- 21849737
TI  - Initial stability of a new uncemented short-stem prosthesis, Spiron(r), in dog
      bone.
AB  - BACKGROUND: Use of the proximal part of the femur in total hip arthroplasty
      enables preservation of the distal femur for later revisions. To use this
      advantage, different types of short-stem prosthesis have been developed in recent
      years. Although cementless hip arthroplasty is not common in the treatment of
      canine osteoarthritis, the use of cementless short-stems might be an alternative
      therapy. The new cementless short-stem prosthesis called Spiron(r) is self
      tapping, and is constructed with a conical shape with threads. We measured the
      relative motion in the bone/prosthesis interface with specified loads in the
      femora of dogs to investigate two aspects: the primary stability of two systems
      of uncemented prosthesis with different principles of anchoring, and the
      theoretical use of the Spiron(r) in dog bone. We measured the cyclic behaviour
      (i.e., reversible, elastic), subsidence (i.e., irreversible, plastic, migration)
      and maximal applied load. METHODS: Twenty-four pairs of fresh femur bones from
      adult German shepherd dogs were used. After measuring the total bone mineral
      density (TBMD), 16 bones were used in each of the short-stem prosthesis group
      (group A), the Zweymuller prosthesis group (group B), and the no-prosthesis
      control group (group C). Micromotion between bone and prostheses was measured for
      16,200 N axial load steps, beginning with 200 N and increasing to 3000 N (1600
      cycles/femur). Simple analysis of variance and non-parametric tests were used to
      compare the groups. RESULTS: The Spiron prosthesis had significantly less motion
      in the bone/prosthesis interface compared with the Zweymuller prosthesis.
      CONCLUSIONS: The new principle of anchoring of the Spiron short-stem prosthesis
      may provide higher primary stability compared with conventional techniques. The
      findings of this study support the assumption that the use of the Spiron
      prosthesis to treat osteoarthritis in the dog is feasible.

PMID- 21849739
TI  - Biosensors.

PMID- 21849740
TI  - Remote healthcare monitoring and assessment.

PMID- 21849742
TI  - Care work.

PMID- 21849743
TI  - Identity cues and dementia in nursing home intervention.
AB  - This study examines the identity cues that family caregivers and healthcare
      personnel use with seniors living with dementia and living in nursing homes. The
      identity cues represent biographical knowledge used to stimulate the dementia
      sufferer, trigger signals and incite interaction. Our grounded approach hinges on
      three objectives: to identify and categorize identity cues; to document their
      uses; and to gain a better understanding of their effectiveness. We interviewed
      nine family caregivers and 12 healthcare workers. Qualitative data indicates that
      the participants use identity cues that evoke seniors' sociological, relational
      and individual characteristics. These identity cues play a central role in
      communication and constitute important information that the family caregivers can
      share with healthcare personnel. They sustain memory, facilitate care and
      reinforce seniors' self-value. These results help to define identity, foster a
      greater role for family caregivers, and constitute a sound basis for the
      implementation of personalized interventions.

PMID- 21849744
TI  - Care work versus career work: sibling conflict over getting priorities right.
AB  - As the average age of the Canadian population continues to increase, and
      providing care at home to frail older adults becomes ever more prevalent, support
      for family and friend caregivers remains a key social policy issue. Economic
      support is an important consideration given the impact of caregiving on labour
      force participation. Yet the caregiving/paid work relationship is not always
      straightforward. While caregiving often restricts employment, limited attachment
      to employment may also influence the decision to provide care. Isabel's story,
      collected as part of a study of sibling views of fairness in sharing parent care
      as well as parent assets, provides a case study in how siblings give different
      priority to care work versus career work and what support needs arise including
      those related to sibling conflict over differing priorities. Isabel claims she
      sacrificed her career to care for her ailing mother while her siblings argue that
      through caregiving, Isabel was sheltered from the paid workforce.

PMID- 21849746
TI  - Elder care and the impact of caregiver strain on the health of employed
      caregivers.
AB  - OBJECTIVE: As the baby-boom generation moves towards middle age, and their
      parents toward old age, the number of employees who combine care for an elderly
      dependant and work will increase in number. These employees are "at risk" of
      experiencing caregiver strain. This paper advances our understanding of these
      trends by examining the relationship between caregiver strain and the health of
      employed caregivers. PARTICIPANTS: Our study involved the analysis of data from
      the 2001 Canadian National Work, Family and Lifestyle Study (N= 31,517). METHODS:
      MANOVA was used to determine the relationship between caregiver strain and three
      situational factors: (1) gender; (2) where the care recipient lives compared to
      the caregiver; and, (3) family type. Regression was used to determine the
      relationship between caregiver strain and mental health. RESULTS: We found that
      caregiver strain depends on gender, family type and location of care. Emotional
      strain was a significant predictor of mental health. CONCLUSIONS: These findings
      support the need for organizations to expand their thinking around work-life
      balance to include employees who have eldercare responsibilities.

PMID- 21849745
TI  - Key issues in human resource planning for home support workers in Canada.
AB  - OBJECTIVE: This paper is a synthesis of research on recruitment and retention
      challenges for home support workers (HSWs) in Canada. PARTICIPANTS: Home support
      workers (HSWs) provide needed support with personal care and daily activities to
      older persons living in the community. METHODS: Literature (peer reviewed,
      government, and non-government documents) published in the past decade was
      collected from systematic data base searches between January and September 2009,
      and yielded over 100 references relevant to home care human resources for older
      Canadians. RESULTS: Four key human resource issues affecting HSWs were
      identified: compensation, education and training, quality assurance, and working
      conditions. To increase the workforce and retain skilled employees, employers can
      tailor their marketing strategies to specific groups, make improvements in work
      environment, and learn about what workers value and what attracts them to home
      support work. CONCLUSIONS: Understanding these HR issues for HSWs will improve
      recruitment and retention strategies for this workforce by helping agencies to
      target their limited resources. Given the projected increase in demand for these
      workers, preparations need to begin now and consider long-term strategies
      involving multiple policy areas, such as health and social care, employment,
      education, and immigration.

PMID- 21849747
TI  - Assembly-line care: ancillary care work in post-Fordist economies.
AB  - OBJECTIVES: In the United States, health care aid is one of the fastest growing
      jobs. This trend is observed in many other Western countries experiencing
      increased demands for home and facility-based long-term care. However, the
      recruitment and retention of workers is difficult. The goal of this research is
      to provide a sound conceptual analysis of paid ancillary care as a better
      understanding of this type of labour can help improve the delivery and quality of
      services as well as the retention of workers. METHODS: The activities of paid
      ancillary care are analysed using Marx's analysis of labour and Habermas's
      distinction of action types. Studies on care workers as well as the manner in
      which the provision of care is structured by agencies are examined in order to
      highlight how care work is perceived. CONCLUSIONS: Although care labour is
      situated in a post-Fordist economy, it is, nonetheless organised as assembly-line
      work reminiscent of Fordist labour. This is in part a consequence of the
      reduction of care to a commodity. The commodification of care erases the
      relational component intrinsic to adequate caring. It is suggested that care
      labour should be structured to support the complex activities that comprise this
      type of labour.

PMID- 21849748
TI  - A model for the development of Caregiver Networks.
AB  - OBJECTIVE: To describe a novel model for the development of Caregiver Networks
      that is based on the notion of partnership. METHODS: We describe the background
      rationale and key elements of the Model in order to assist individuals in
      developing new Caregiver Networks and respite mechanisms. PARTICIPANTS:
      Provincial/territorial/state health and social service systems, unpaid caregivers
      (family members or friends) and care recipients (ill or disabled individuals
      across cultures and age groups) in a network partnership. RESULTS: We
      demonstrated in this model that Caregiver Networks is a shared responsibility
      among partner members for development and evaluating network and respite care
      mechanisms. CONCLUSION: The model for developing Caregiver Networks is at the
      stage of implementation. The authors welcome opportunities to conduct pilot
      projects to evaluate this Model.

PMID- 21849749
TI  - End-of-life healthcare decision-making: the intermediary role of the ethicist in
      supporting family caregivers and health professionals.
AB  - OBJECTIVE: Family support in end-of-life decision-making is critical, yet this
      issue receives little attention. The purpose of this research is to provide
      insight into how the clinical ethicist can effectively support family caregivers
      when making end-of-life healthcare decisions. It further suggests how the
      clinical ethicist can provide support to other healthcare professionals who work
      with family caregivers in making end-of-life healthcare decisions. PARTICIPANTS
      AND METHODS: Using a grounded theory approach, a theoretical sampling of 20
      family caregivers previously involved in end-of-life decision-making were
      interviewed. Semi-structured in-depth interviews were audiotaped, and
      transcribed. RESULTS: Interviews were analyzed using a constant comparative
      approach. The analysis resulted in the identification of three categories related
      to the experience of decision-making: the impact of healthcare decision-making on
      individual and family well-being, the effectiveness of healthcare professionals
      in supporting families, and the role of the ethicist. CONCLUSIONS: The results
      demonstrated the challenges that family members encounter when faced with end-of
      life decision-making. The participants identified the importance of having access
      to a clinical ethicist who, with objectivity and specific training, can better
      meet the needs of family caregivers and improve the process of decision-making at
      the end-of-life.

PMID- 21849750
TI  - Health promoting leadership - different views of the concept.
AB  - OBJECTIVE: To describe and analyse different views of health promoting leadership
      among actors involved in workplace health promotion in eight Swedish
      municipalities. METHODS: Twenty individuals were interviewed and their views were
      analysed according to the methodology of phenomenograpic research, exploring how
      health promoting leadership was described, what motives were expressed, and what
      critical conditions were perceived for developing such leadership. RESULTS: The
      informants described health promoting leadership in three ways: organising health
      promoting activities, having a supportive leadership style, and developing a
      health promoting workplace. The motives mentioned for developing health promoting
      leadership were instrumental motives and improved health. The critical conditions
      for health promoting leadership were organisational conditions, characteristics
      of individual managers, and support to managers. CONCLUSIONS: It seems that the
      concept of health promoting leadership was often used to link ideas about good
      leadership to the health of employees. Organisational goals and management trends
      may also have influenced the motives as well as the conditions for development of
      health promoting leadership.

PMID- 21849751
TI  - Factors affecting burnout and work engagement in teachers when entering
      employment.
AB  - OBJECTIVE: When entering employment many beginning teachers experience a reality
      shock and a crisis of competence. These two factors, in combination with high
      levels of job demands and low levels of job resources, may lead to the
      development of burnout. The purpose of the study was to investigate how
      individual characteristics, the educational context, and the work context
      predicted levels of burnout and work engagement during this transition period.
      PARTICIPANTS: The sample consisted of 1290 beginning teachers from Sweden.
      METHODS: Data were collected using surveys during the final year of education and
      during the initial period of employment. Data were analyzed using hierarchical
      regression. RESULTS: Job demands, job resources, and spillover between private
      life and work accounted for the largest amount of explained variance in both
      burnout and work engagement. Job demands were more strongly related to burnout,
      whereas job resources more strongly related to work engagement. The predictors
      with the greatest relative influence on both burnout and work engagement were
      unmet expectations and mastery of skills. CONCLUSIONS: The results support the
      importance of the work context's impact on burnout and work engagement.
      Additionally, the interaction between private life and work should be further
      studied in future studies.

PMID- 21849752
TI  - Safety performance: the mediating role of safety control.
AB  - OBJECTIVE: Occupational stress models suggest that the ability to understand,
      predict, and control stressful events minimizes their impact. This study examines
      the applicability of the stress antidote theory to the safety environment. Newly
      developed measures assess understanding why and how unsafe events occur,
      predicting the occurrence of unsafe events, and controlling unsafe events, and
      how these constructs relate to safety performance at work. In addition, the role
      of supervisor safety support is explored. PARTICIPANTS: 424 employees in the
      Facilities department at a large university. METHODS: Measures were developed
      based on existing literature and focus groups, and participants completed a
      survey about their safety experiences at work. RESULTS: Analyses conducted using
      structural equation modeling indicate that safety understanding, safety
      prediction, and safety control are related but distinct variables. Safety
      understanding affects safety performance through safety control, while supervisor
      support for safety affects safety performance both directly and indirectly
      through control. CONCLUSION: Lack of understanding of safety or inability to
      predict dangerous outcomes may be necessary but not sufficient to explain unsafe
      workplace behaviors. Employees' safety behaviors may be more directly influenced
      by the extent to which they have the power to control safety in their work
      environment.

PMID- 21849755
TI  - Voiding dysfunction after the tension-free vaginal tape procedure.
AB  - AIM: To assess the incidence of voiding dysfunction in women undergoing a tension
      free vaginal tape (TVT) procedure and report our experience with nonsurgical and
      surgical management. METHODS: Pre- and postoperative introital ultrasonographic
      measurement of the residual volume was performed in a prospective observational
      study. Patients' perception of micturition and continence status was assessed by
      questionnaire. RESULTS: Of 478 women, 4 (0.8%) suffered from micturition
      disturbance within the first 2 weeks. In the mean of 3 months after surgery, 7.1%
      of the patients had residual volume between 50 and 100 ml, and 2.6% had residual
      volume >100 ml. 243 women were investigated after 39 months (range 12-74). The
      rate of residual volume exceeding 50 ml decreased to 6.5% and was approximated to
      the preoperative period. CONCLUSION: Incomplete bladder emptying is a possible
      problem after TVT. In our cohort, 93% of the women had no voiding disturbances or
      marginally affected voiding after 12-74 months.

PMID- 21849756
TI  - Resident duty-hour restrictions and their effect on operative experience in
      obstetrics and gynecology.
AB  - BACKGROUND/AIMS: To determine the effect of duty-hour restrictions on the
      operative experience of obstetrics and gynecology residents. METHODS: Operative
      numbers were obtained from graduates of Mayo Clinic (Rochester, Minn., USA) and
      Good Samaritan Hospital (Cincinnati, Ohio, USA). Mean operative numbers between
      graduates in 2007 and 2003 were compared. The following procedures were
      evaluated: spontaneous vaginal delivery, forceps-assisted vaginal delivery,
      vacuum-assisted vaginal delivery, cesarean delivery, surgery on antenatal
      patients, amniocentesis, total abdominal hysterectomy, total vaginal
      hysterectomy, laparotomy, incontinence or pelvic floor surgery, operative
      laparoscopy, hysteroscopy, cervical conization, and surgical sterilization. The
      number of procedures performed (total and as the primary surgeon) were evaluated.
      We analyzed each institution's residents separately. RESULTS: At Mayo Clinic, the
      2007 graduates performed significantly fewer conizations than the 2003 graduates
      (p = 0.006). At Good Samaritan Hospital, the 2007 graduates performed
      significantly more vacuum-assisted vaginal deliveries (p = 0.002), cesarean
      deliveries (p = 0.002), and sterilizations (p < 0.001) than the 2003 graduates.
      The above findings were unchanged when evaluating procedures for which the
      resident was the primary surgeon. CONCLUSION: Duty-hour restrictions have not
      adversely affected the operative experience of obstetrics and gynecology
      residents. No significant differences in the number of the spontaneous vaginal
      deliveries, abdominal hysterectomies, or vaginal hysterectomies performed were
      observed.

PMID- 21849757
TI  - Interpregnancy body mass index changes and risk of stillbirth.
AB  - BACKGROUND/AIMS: To examine the association between interpregnancy body mass
      index (BMI) change and stillbirth. METHODS: Retrospective study using Missouri
      maternally linked cohort files (1978-2005). A total of 218,389 women were used in
      the analysis. BMI was classified as: underweight (<18.5), normal (18.5-24.9),
      overweight (25-29.9), or obese (>=30.0). Weight change was defined based on BMI
      category (i.e. normal-normal, normal-obese, etc.). Cox proportional hazard
      regression models were used to generate adjusted hazard ratios (HR) and 95% CI
      for the risk of stillbirth in the second pregnancy. RESULTS: Significant findings
      were associated with interpregnancy BMI changes involving overweight mothers
      becoming obese (HR = 1.4, 95% CI 1.1-1.7), normal-weight mothers becoming
      overweight (HR = 1.2, 95% CI 1.0-1.4) or obese (HR = 1.5, 95% CI 1.1-2.1), or
      obese mothers maintaining their obesity status across the two pregnancies (HR =
      1.4, 95% CI 1.2-1.7). Other weight change categories did not show significant
      risk elevation for stillbirth. CONCLUSIONS: BMI change appears to play an
      important role in subsequent stillbirth risk.

PMID- 21849758
TI  - Fournier gangrene: our approach and patients.
AB  - AIM: This retrospective analysis presents our experience in treating Fournier
      gangrene (FG) and aims to bring in focus diagnostic and therapeutic problems as
      well as early and aggressive treatment. PATIENTS AND METHODS: A total of 16 male
      patients were included in the study. The gastrointestinal form was seen in 5 and
      the urogenital form in 11 patients. The subjects ranged in age from 39 to 74
      years (average 61) for the urogenital, and from 48 to 72 (average 58) for the
      gastrointestinal form. Other conditions were seen in 9 patients (diabetes
      mellitus was most common). Most patients were infected with several bacteria. We
      performed colostomy in 1 patient, orchidectomy in 2 patients, cystostomy in 2
      patients and penis amputation in 1 patient. Ultrasound-guided biopsy or
      aspiration, and CT was also used. Aggressive surgical necrectomy and aggressive
      antimicrobial therapy was used. RESULTS: Treatment was successful in 14 of 16
      patients (87.5%). The length of hospitalization was 19-58 days (average 48) for
      the urogenital form and 24-56 days (average 41) for the gastrointestinal form.
      Mortality was 12.5%. A lethal outcome was recorded in two patients infected with
      methicillin-resistant Staphylococcus aureus. The average time between onset and
      hospitalization was 3-11 days (5 on average) for urogenital FG and 4-10 days
      (average 6) for gastrointestinal FG. Treatment was significantly longer in
      patients with a comorbidity, such as diabetes or liver cirrhosis due to alcohol
      abuse. CONCLUSION: Early diagnosis as well as intensive and aggressive treatment
      are key to successful treatment of FG. Comorbidity increases length of therapy
      and lowers the chance for recovery. Disease can be seen again several years after
      the initial outburst.

PMID- 21849759
TI  - Outcome of antegrade radical prostatectomy with intended wide resection in
      prostate cancer patients with a preoperative serum PSA level >100 ng/ml.
AB  - OBJECTIVE: It was the aim of this study to assess the outcome of prostate cancer
      patients with preoperative prostate-specific antigen (PSA) levels >=100 ng/ml who
      were treated with antegrade radical prostatectomy with intended wide resection
      (aRP). PATIENTS AND METHODS: Eighteen patients who underwent aRP had an initial
      PSA level >=100 ng/ml. Overall survival, disease-specific survival and
      biochemical progression-free survival (bPFS) rates were determined, and
      predictors of treatment outcome were examined. RESULTS: The median serum PSA
      level was 159.5 ng/ml. All patients but one had received neoadjuvant androgen
      deprivation therapy (ADT), while only 2 patients received adjuvant ADT. Five
      patients were classified as stage pT2, 6 as pT3a, 6 as pT3b and 1 as pT4. Four
      patients had locoregional lymph node metastases. Twelve patients developed PSA
      failure. Eight of them received salvage ADT. The estimated 10-year bPFS rate was
      25.0% and the overall survival and disease-specific survival rates were 92.9 and
      100%, respectively, at a median follow-up of 6 years. Multivariate analysis
      revealed only the clinical stage to be predictive of bPFS based on preoperative
      variables. On the other hand, surgical margin status, extracapsular extension and
      organ-confined disease were identified as being significant postoperative
      predictors. CONCLUSIONS: This study showed a comparatively satisfactory outcome
      for clinically non-metastatic prostate cancer with PSA levels >=100 ng/ml treated
      by aRP.

PMID- 21849760
TI  - Predicting the risk of high-grade bladder cancer using noninvasive data.
AB  - AIM: To examine the hypothesis that the risk of high-grade bladder cancer can be
      predicted using noninvasively obtained data. PATIENTS AND METHODS: We
      retrospectively analyzed the database of 431 patients that had transurethral
      resection of first-time bladder tumors between June 1998 and December 2009. Pre
      operative parameters evaluated were: patients' age; gender; sonographic tumor
      diameter, number and location of tumor inside the bladder; presence of
      hydronephrosis, and results of urinary cytology. Parameters that showed
      significance in multivariate analysis were incorporated into the nomogram.
      RESULTS: Multivariate analysis of the data showed that patient's age, the
      presence of hydronephrosis, sonographic tumor diameter (risk of a high-grade
      tumor: 14, 29, 43.3, 55.7 and 69.4% at diameters: 0.5-1.5, 1.6-2, 2.1-2.5, 2.6-3
      and >3 cm, respectively), location of tumor in the bladder (risk of high-grade
      tumor: 28.8, 47, 67.5 and 90.5% in the lateral walls, posterior/base, anterior
      and dome, respectively), and urinary cytology were all highly significant and
      independent predictors of high-grade tumors. A nomogram constructed using these
      variables scored an area of 0.853 in the ROC curve. CONCLUSIONS: The risk of high
      grade bladder tumor can be accurately predicted using non-invasively obtained
      information. This prediction can help to triage patients with newly detected
      bladder cancer for biopsy.

PMID- 21849761
TI  - Directional indicator on neural oscillations as a measure of synaptic plasticity
      in chronic unpredictable stress rats.
AB  - To examine whether the directionality index of neural information flow (NIF) over
      specific oscillatory bands is useful in measuring synaptic plasticity, we
      employed the IM approach to determine the direction of NIF between the cortex and
      thalamus in normal and stressed animals. The experiment was performed by inducing
      long-term potentiation (LTP) of the thalamocortical pathway after recording local
      field potential (LFP). Additionally, comparison of IM measurement between broad-
      and narrowbands was performed, while a numerical study was also carried out for
      assessing the number of data points. The results show that the instantaneous
      phases extracted from narrowband vary monotonically, while these phases are
      jagged in broadband. Our data show that there is a predominant driving effect
      (coupling directional index d >0) from the thalamus to the frontal cortex in
      normal animals; however, the value of d is significantly reduced in the chronic
      stressed group in both the delta and theta bands. Furthermore, the field LTP data
      show that chronic stress decreases medial prefrontal cortex synaptic plasticity,
      which is certainly in line with the LFP findings. Together, these data suggest
      that using an IM algorithm, the directionality index of NIF in specific
      oscillatory frequency bands will probably be used as a measure of synaptic
      plasticity.

PMID- 21849762
TI  - Normal reference ranges of ductus venosus Doppler indices in the period from 14
      to 40 weeks' gestation.
AB  - OBJECTIVE: To construct reference ranges of ductus venosus (DV) Doppler indices
      in normal singleton pregnancies. METHODS: A cross-sectional study was conducted
      on low-risk singleton pregnancies with accurate gestational age, and normal
      fetuses were enrolled into the study. Measurements of DV Doppler indices were
      determined by experienced sonographers. Poor quality images were excluded.
      RESULTS: A total of 640 fetuses underwent DV measurements, ranging from 13 to 30
      for each gestational week. The relationship between gestational age and DV
      Doppler indices was not linear. The best-fit regression equations are as follows:
      preload index = (5.061 - 0.4882) * exp (-0.211 * GA) + 0.4882; peak velocity
      index for veins = (7.498 - 0.5609) * exp (-0.2184 * GA) + 0.5609; pulsatility
      index for veins = (17.9 - 0.6053) * exp (-0.2512 * GA) + 0.6053; systolic/atrial
      wave ratio = (300 - 2.124) * exp (-0.3649 * GA) + 2.124. Notably, during the
      period from 14 to 20 weeks' gestation, all of the four indices rapidly decreased
      and they were relatively stable or slightly decreased after that. The nomogram
      tables for various percentile ranges were constructed. CONCLUSION: A nomogram for
      DV Doppler indices for each gestational week during the period from 14 to 40
      weeks' gestation was established. These reference ranges may be a useful non
      invasive tool for evaluation of fetal cardiac function.

PMID- 21849763
TI  - Double unfurled dartos flap technique in the surgical treatment of recurrent
      urethrocutaneous fistulas.
AB  - BACKGROUND: The management of recurrent urethrocutaneous fistula (RUCF) is a
      challenging problem that poses a serious difficulty for the hypospadias surgeon.
      We report here a novel technique in which a double unfurled dartos subcutaneous
      flap is utilized in the treatment of patients with RUCF. METHODS: We
      retrospectively reviewed the records of all our patients who underwent surgical
      treatment of urethrocutaneous fistula with this new operative method after
      previously failed fistula repair. The main novelty of this technique is the use
      of two opposite medium thickness flaps, unfurled from the inner surface of the
      dartos fascia and spread over the fistula and each other so as to cover the
      urethral suture line completely, and fixed to the surrounding corporal tissue.
      RESULTS: Eight patients with 11 RUCFs (with localizations varying from subcoronal
      to penoscrotal fistula opening) underwent surgical correction with the new
      method. There had previously been at least 3 recurrences in 6 of these patients,
      and different closure techniques had been used. RUCF diameter was <4 mm in all
      patients. Surgery was performed at the earliest following a 6-month healing
      period since the last fistula repair attempt. All of the RUCFs were repaired
      successfully with the technique. After a follow-up of at least 6 months, none of
      the 8 patients had developed recurrence of the fistula, and there were no
      postoperative complications. CONCLUSION: The double unfurled dartos subcutaneous
      flap method appears to be a simple and appropriate procedure with which to repair
      recurrent mid-shaft and proximal urethral fistulas after failed hypospadias
      repair.

PMID- 21849764
TI  - Fetal surgery for myelomeningocele: patient selection, perioperative management
      and outcomes.
AB  - Myelomeningocele (MMC), one of the most common congenital malformations, can
      result in severe lifelong disabilities,including paraplegia, hydrocephalus,
      Chiari II malformation(CM-II), incontinence, sexual dysfunction, skeletal
      deformations and mental impairment. MMC was the first nonlethal anomaly to be
      treated by fetal surgery. Experimental and clinical evidence suggests that the
      primary cause of the neurologic deficit associated with MMC is not simply
      incomplete neurulation but rather chronic mechanical injury and amniotic fluid
      induced chemical trauma that progressively damages the exposed neural tissue
      during gestation. Case series and a prospective, randomized study show that fetal
      surgery for MMC before 26 weeks' gestation may preserve neurologic function,
      reverse the hindbrain herniation of the CM-II and obviate the need for postnatal
      placement of a ventriculoperitoneal shunt. However, these studies also
      demonstrate that fetal surgery is associated with significant maternal and fetal
      risks. Consequently, further research is warranted to further expand our
      understanding of the pathophysiology of MMC, to evaluate the long-term impact of
      in utero intervention and to refine the timing and technique of fetal MMC
      surgery.

PMID- 21849765
TI  - Current experience and prospect of internet consultation in fetal cardiac
      ultrasound.
AB  - OBJECTIVE: Internet consultation with volume ultrasound is one of the strategies
      studied to attempt to improve prenatal detection of congenital heart defects
      (CHD). METHODS: This methodology is a form of telemedicine in which a volume
      block of the fetal heart (either static 3D or STIC volume dataset) is acquired by
      an operator (non-expert) and transmitted via internet for remote consultation.
      Naturally, this methodology is suitable for remote locations or those with less
      access to specialists able to confirm or rule out a prenatal diagnosis of CHD.
      RESULTS: The use of internet consultation demonstrates that some intracardiac
      anomalies can be ruled out and others confirmed, thus enabling the parents to
      prepare for the likely outcome of the pregnancy and to modify the perinatal
      management. CONCLUSION: Internet consultation offers a good alternative for
      fetuses from more isolated locations with a high risk of CHD. Moreover, this
      methodology could become an interesting tool for distance learning and training.

PMID- 21849766
TI  - Changes in fetal circulation associated with congenital heart disease and their
      effects on fetal growth.
AB  - OBJECTIVE: Our aim was to investigate the association between fetal growth and
      cerebrovascular resistance in fetuses with congenital heart disease (CHD).
      METHODS: Fetal echocardiography was performed to measure the biparietal diameter,
      abdominal circumference, femur length, estimated fetal body weight, middle
      cerebral artery (MCA) resistance index (RI) and umbilical artery (UA) RI in 44
      fetuses with CHD and 140 normal fetuses at a gestational age of 28-34 weeks.
      RESULTS: Fetuses with CHD exhibited significantly lower values for femur length,
      estimated fetal body weight at the third trimester, body weight, length, and
      chest circumference at birth than normal controls. The percentages of fetuses
      showing MCA RI values <10th percentile and UA RI values >90th percentile were
      significantly higher in the CHD group than in the control group. However, there
      were no significant differences in any biometric parameters measured between
      cases with MCA RI values >=10th percentile and values <10th percentile.
      CONCLUSIONS: Growth restriction and blood flow changes were observed
      significantly more frequently in fetuses with CHD than in those without CHD.
      Further studies are necessary to clarify the association between fetal growth and
      dynamic changes in fetal circulation.

PMID- 21849767
TI  - Endoscopic removal of an intravesical calcified sling using pneumatic lithotripsy
      and cystoscopic resection.
AB  - The transobturator tape procedure is a minimally invasive treatment for stress
      urinary incontinence. The widespread use of these slings has led to an increase
      in the number of rare complications, such as bladder erosion. Although in the
      last few years several minimally invasive techniques have been described,
      surgical management of such complications remains an open issue. We report a case
      of a bladder stone formed on a transobturator sling after unrecognized bladder
      perforation. Using pneumatic lithotripsy, the calculus was fragmented and the
      intravesical portion of the tape was successfully excised and removed by
      transurethral resection and endoscopic scissors. This minimally invasive
      transurethral technique is challenging but can be a safe and successful way to
      deal with such rare complications.

PMID- 21849768
TI  - Methylaminolaevulinic acid photodynamic therapy in the treatment of erythroplasia
      of Queyrat.
AB  - BACKGROUND: Erythroplasia of Queyrat (EQ) is an intra-epithelial carcinoma of the
      penis. Progression to invasive carcinoma may occur. Its cause is unknown but some
      evidence suggests infection with human papillomavirus in the pathogenesis of EQ;
      however, recent data do not confirm this. Therapy is difficult and associated
      with important recurrence rates. Photodynamic therapy (PDT) employs a
      photosensitizer excited by visible light. The resulting photodynamic reaction
      selectively destroys atypical cells. Only few reports exist on the use of topical
      PDT in the treatment of EQ. OBJECTIVE: We report 11 cases of EQ treated by
      topical methylaminolaevulinic acid (MAL) PDT. RESULTS: Out of 11 male patients
      with EQ treated by topical MAL-PDT, 3 achieved complete remission sustained for
      24 and 51 months and 4 a partial remission sustained for 2-45 months with a
      follow-up period of 4-45 months (1 patient lost to follow-up); surprisingly, 2 of
      the 4 patients with partial remission presented a complete remission after 20 and
      45 months of follow-up, respectively, without further therapy. Four patients
      showed progression of the disease. CONCLUSION: Whereas topical MAL-PDT offers the
      advantages of tumour specificity, preservation of function and a good cosmetic
      result, side effects may cause treatment discontinuation in some cases. Treatment
      of EQ with PDT may represent a valuable option in selected cases, but our data do
      not allow considering it as a first-line therapeutic option.

PMID- 21849769
TI  - A recurrent nonsense mutation occurring as a de novo event in a patient with
      recessive dystrophic epidermolysis bullosa.

PMID- 21849770
TI  - The socioeconomic status of subjects: a prominent feature contributing to the
      phenotypical approach to COPD.

PMID- 21849771
TI  - Complete remission with a combination of lenalidomide, cyclophosphamide and
      prednisolone in a patient with incomplete POEMS syndrome.

PMID- 21849772
TI  - Indoxyl sulfate induces epithelial-to-mesenchymal transition in rat kidneys and
      human proximal tubular cells.
AB  - BACKGROUND/AIMS: Indoxyl sulfate (IS) is a uremic toxin that accelerates the
      progression of chronic kidney disease (CKD). This study aimed to determine if IS
      induces epithelial-to-mesenchymal transition (EMT) in the kidneys of hypertensive
      rats and human proximal tubular cells (HK-2). METHODS: EMT was evaluated by
      immunohistochemistry, reverse transcription-polymerase chain reaction and
      immunoblotting of the epithelial markers E-cadherin and zonula occludens-1 (ZO
      1), and the mesenchymal marker alpha-smooth muscle actin (alpha-SMA). Rat groups
      consisted of (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt
      resistant normotensive IS-administered rats (DN+IS), (3) Dahl salt-sensitive
      hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive IS-administered
      rats (DH+IS). HK-2 cells were incubated with or without IS. RESULTS: In kidneys,
      DH rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression
      of alpha-SMA compared with DN rats. DN+IS and DH+IS rats showed reduced
      expression of E-cadherin and ZO-1, and enhanced expression of alpha-SMA compared
      with DN and DH rats, respectively. DH+IS and DH rats showed increased Masson's
      trichrome-positive fibrosis areas compared with DH and DN, respectively. IS
      treated HK-2 cells showed reduced expression of E-cadherin and ZO-1, and enhanced
      expression of alpha-SMA. CONCLUSION: IS induces EMT in the kidneys of
      hypertensive rats and in human proximal tubular cells.

PMID- 21849773
TI  - Elevated white blood cell count worsens proteinuria but not estimated glomerular
      filtration rate: the Kansai Healthcare Study.
AB  - BACKGROUND/AIMS: No prospective studies have estimated the association between
      white blood cell (WBC) count and the risk of proteinuria. We prospectively
      examined the relationships of WBC count, as a marker of inflammation, with two
      outcomes: proteinuria and low estimated glomerular filtration rate (eGFR).
      METHODS: We enrolled 10,008 Japanese men aged 40-55 years who had neither
      proteinuria nor low eGFR and were not taking antihypertensive medications at
      entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was
      defined if eGFR was <60 ml/min/1.73 m(2). RESULTS: During the 49,644 person-years
      of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age,
      body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood
      pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure
      time physical activity and eGFR, the highest quintile (>=7.51 * 10(3)/MUl) of WBC
      count was independently associated with an increased risk of incidence of
      proteinuria [HR: 1.45 (95% CI: 1.23-1.73)] compared with the lowest quintile
      (<=4.80 * 10(3)/MUl). On the other hand, during 52,833 person-years, we confirmed
      439 cases of low eGFR. In multivariate models, there was no association between
      WBC count and low eGFR. CONCLUSION: Elevated WBC count was independently
      associated with an increased risk of proteinuria, but not low eGFR.

PMID- 21849774
TI  - Vertebral artery involvement by tympanojugular paragangliomas: management and
      outcomes with a proposed addition to the fisch classification.
AB  - OBJECTIVES: To present the management and outcomes of cases of tympanojugular
      paraganglioma (TJP) with vertebral artery (VA) involvement, and to propose the
      addition of the new 'V' category to the Fisch classification. MATERIALS AND
      METHODS: Retrospective analysis of data from a quaternary neuro-otologic and
      skull base referral center. We studied 230 TJP patients to identify the cases
      with VA involvement and present their management, surgical findings and outcome.
      RESULTS: Out of 230 patients, 8 patients were found to have VA involvement by
      TJP. The extradural artery was involved in 1 patient and the intradural VA was
      involved in 6 patients. The intradural and extradural VA were simultaneously
      involved in 1 patient. Seven of the 8 patients underwent surgery. In 2 patients,
      preoperative occlusion was performed (1 with balloon, 1 with coils). In 5 of
      these 7 patients, the tumor was successfully separated from the VA by
      microdissection with or without endovascular intervention. In another patient,
      the tumor together with the involved VA was removed. Of 7 patients who had
      surgery, 1 patient did not undergo endovascular intervention and had subtotal
      tumor removal from the VA. There were no serious complications in removing the
      tumor from around the VA. CONCLUSION: Although uncommon, the intradural or
      extradural VA can be involved by TJP. To avoid vascular accidents, the VA should
      be thoroughly evaluated at the planning stage. We advocate that the addition of a
      'V' category would help to identify patients who need individualized VA
      management as part of a complete surgical evaluation.

PMID- 21849775
TI  - Hypokalemia is associated with increased mortality rate in chronic hemodialysis
      patients.
AB  - BACKGROUND: Both hypokalemia (hypoK) and hyperkalemia (hyperK) are life
      threatening to hemodialysis (HD) patients. This study was conducted to compare
      their clinical characteristics and long-term survival. METHODS: Patients were
      divided into three groups according to the last mid-week predialysis serum
      potassium concentrations: hypoK (<3.5 mEq/l), normoK (between 3.5 and 5.5 mEq/l),
      and hyperK (>5.5 mEq/l). The maximal duration of the follow-up period was 54
      months. RESULTS: Compared with the hyperK group,patients in the hypoK group were
      older (p <0.05), had a higher incidence of comorbidity factors, less body weight
      gain prior to HD (p < 0.05), lower body mass index (BMI, p < 0.05), and higher
      BUN to creatinine ratio and hs-CRP (p < 0.05). The serum albumin and prealbumin
      concentrations were also lowest in the hypoK group, compared with the normoK and
      hyperK groups, respectively (all p < 0.001). A similar finding was also obtained
      for the normalized protein catabolism rate (nPCR, p < 0.001) among the three
      groups. Positive linear correlations between serum albumin and potassium
      concentration were only found in the hypoK and normoK groups (p < 0.001).
      Multiple logistic regression analysis showed that hypoalbuminemia, low BUN, and
      phosphate concentrations were significantly correlated with hypoK. HypoK patients
      also had a lower cumulative survival rate than hyperK patients. CONCLUSION: HypoK
      HD patients, with lower serum levels of albumin, prealbumin, nPCR, and BMI, but
      higher level of hs-CRP, showed a malnutritional and inflammatory status, and
      caused increased mortality rate.

PMID- 21849776
TI  - Body mass index, initial neurological severity and long-term mortality in
      ischemic stroke.
AB  - BACKGROUND: Obesity is believed to increase the risks of ischemic stroke or
      coronary heart disease; however, regarding outcome after established vascular
      diseases, recent unexpected evidence has suggested that an increased body mass
      index (BMI) might have beneficial effects (obesity paradox). The aim of this
      study was to evaluate the independent association between BMI and long-term
      mortality after ischemic stroke. METHODS: A total of 1,592 consecutive patients
      with ischemic stroke were prospectively included through our stroke cohort. In
      this study, the levels of BMI were classified based on guidelines for the Asian
      Pacific population. Initial neurological severity was estimated by the National
      Institutes of Health Stroke Scale (NIHSS) score. Information on mortality was
      collected until the end of 2009, and the median follow-up period was 4 years. To
      examine the association between BMI and long-term mortality, we used Cox's
      proportional regression analysis. RESULTS: During follow-up, 23% of patients
      died. Linear regression analysis showed that the level of BMI was inversely
      related to initial neurological severity (p = 0.002). In the model of adjustment
      of age and gender using Cox's proportional regression analysis, this inverse
      trend was also significant (reference, normal weight; hazard ratio of
      underweight, 2.45; overweight, 0.77; obesity, 0.60). However, after adjustment of
      all covariates, including initial neurological severity, only the harmful effect
      of underweight remained significant (2.79; 95% CI, 1.92-4.05); however,
      beneficial effects of overweight and obesity did not. CONCLUSION: Our study
      showed that an independent association between BMI and long-term mortality after
      ischemic stroke was found only in underweight patients. The obesity paradox
      phenomenon seems to be limited, and might not be interpreted as a direct causal
      relationship due to a strong association with initial neurological severity.

PMID- 21849777
TI  - Off-label thrombolysis for acute ischemic stroke: rate, clinical outcome and
      safety are influenced by the definition of 'minor stroke'.
AB  - BACKGROUND: Several contraindications for intravenous thrombolysis are not based
      on controlled trials. Specialized stroke centers often apply less restrictive
      criteria. The aim of our study was to analyze how many patients at our
      institution receive off-label thrombolysis. In addition, clinical outcome and
      safety data were compared to those from patients treated on-label, and the
      influence of different definitions of 'minor stroke' were examined. METHODS:
      Consecutive thrombolysis patients treated between January 2006 and January 2010
      were included. Patients treated off-label were compared to patients given on
      label therapy according to the European license. Since no specified definition
      for 'minor neurological deficit' exists in the license, two distinct definitions
      were considered off-label, i.e. National Institutes of Health Stroke Scale score
      (NIHSSS) <1 (definition 1) and NIHSSS <=4 (definition 2). RESULTS: Of a total of
      422 patients, 232 (55%) were treated off-label. The most prevalent off-label
      criteria (OLCs) were the following: age >80 years (n = 113), minor stroke
      (definition 1, n = 3; definition 2, n = 84), elevated blood pressure
      necessitating aggressive treatment (n = 75), time window >3 h (n = 71) and major
      surgery or trauma within the preceding 3 months (n = 20). In group comparisons,
      off-label patients had an overall worse outcome using definition 1 for minor
      stroke, while there was no difference when definition 2 was applied. In
      multivariate analysis, off-label therapy (definition 1) in general and age >80
      years were independent predictors of poor outcome. None of the contraindications
      were associated with an increased bleeding risk. CONCLUSIONS: Off-label therapy
      is frequently applied at our center and is not associated with higher
      complication rates. Overall outcome of off-label treatment largely depends on the
      definition used for minor stroke. Besides age >80 years, a known poor prognostic
      factor, no other specific OLC was associated with poor outcome. Our data suggest
      that the criteria in the European license may be too restrictive.

PMID- 21849779
TI  - Uncertainties in the assessment of cortical flow by perfusion-weighted MRI in
      acute stroke.

PMID- 21849781
TI  - Severe aphasia following infarction in the territory of the left anterior
      choroidal artery.

PMID- 21849778
TI  - Search for a map and threshold in perfusion MRI to accurately predict tissue
      fate: a protocol for assessing lesion growth in patients with persistent vessel
      occlusion.
AB  - BACKGROUND: The MRI-based mismatch concept has been used to estimate the risk of
      infarction in ischemic stroke. Based on multiple studies on magnetic resonance
      perfusion imaging, it seems unlikely that any perfusion parameter threshold will
      provide a reliable prediction of radiological or clinical outcome for all
      patients. The goal of our study was to find a minimally biased yet maximally
      useful perfusion postprocessing protocol which would offer the treating physician
      a useful estimate of tissue fate. METHODS: One hundred and forty-five acute
      ischemic stroke patients, admitted within 24 h after stroke to the Charite
      University Medicine Hospital in Berlin between March 2008 and November 2009, were
      included in this study. Using three different software packages
      (Perfscape/Neuroscape, PMA and Stroketool), maps of mean transit time, cerebral
      blood flow (CBF) and T(max) were created. Three different thresholds were applied
      on each parameter map and subsequent volumes of hypoperfused tissue were
      calculated. RESULTS: Overall, the maps and thresholds giving the least amount of
      overestimation of the final infarct volume were T(max) 8 s in
      Perfscape/Neuroscape, CBF 20 ml/100 g/min in PMA and CBF 15% (of the highest
      value on the scale for a given patient) in Stroketool. In patients with
      persistent vessel occlusion, a CBF map with a restrictive threshold showed
      volumes of tissue at definite risk of infarction in up to 100% of patients. The
      additional use of a CBF map with a high threshold enabled identification of
      patients without penumbras. CONCLUSIONS: No combination of software, map and
      threshold was able to give a reliable estimate of tissue fate for either all
      patients or any subgroup of patients. However, in patients with vessel occlusion,
      combination of a CBF map with a low and a high threshold can enable calculation
      of the minimum volume of brain tissue that will inevitably be lost if the
      occlusion persists.

PMID- 21849782
TI  - Identification of copy number variants on human chromosome 22 in patients with a
      variety of clinical findings.
AB  - The aims of this study were to create a copy number variant (CNV) profile of
      human chromosome 22 and to establish a genotype-phenotype correlation for
      patients with genomic abnormalities on chromosome 22. Thus, 1,654 consecutive
      pediatric patients with a diversity of clinical findings were evaluated by high
      resolution chromosomal microarray analysis (CMA). We identified 25 individuals
      with abnormal CNVs on chromosome 22, representing 1.5% of the cases analyzed in
      this cohort. Meanwhile, we detected 1,298 benign CNVs on this chromosome in these
      individuals. Twenty-one of the 25 abnormal CNVs and the majority of the benign
      CNVs occurred through involvement of the 8 unstable genomic regions enriched with
      low copy repeats (LCR22A-H). The highly dynamic status of LCR22s within the 22q11
      region facilitates the formation of diverse genomic abnormalities. This CNV
      profile provides a general perspective of the spectrum of chromosome 22 genomic
      imbalances and subsequently improves the CNV-phenotype correlations.

PMID- 21849783
TI  - Clinical, cytogenetic and molecular study in a case of r(3) with 3p deletion and
      review of the literature.
AB  - Ring chromosome 3 is a rare abnormality with only 10 patients described in the
      literature. We report a patient with r(3) and ~6-Mb distal 3p deletion. Single
      nucleotide polymorphism array, multiplex ligation-dependent probe amplification
      and fluorescence in situ hybridization techniques revealed that the ring was
      formed by a break in 3p26.1 and fusion with the subtelomeric region of 3q. The
      patient presents delayed psychomotor development, growth failure, minor anomalies
      and other features similar to patients with 3p monosomy. The analysis of 300
      metaphase cells using G-banding and fluorescence in situ hybridization with
      centromeric probe revealed ring instability resulting in cells with secondary
      aberrations and with ring loss that could also be related to some phenotypic
      characteristics such as growth delay. This is the first patient with r(3) studied
      using molecular techniques that determined the exact breakpoints in order to
      establish a better karyotype-phenotype correlation.

PMID- 21849784
TI  - Variants of HSPA1A in combination with plasma Hsp70 and anti-Hsp70 antibody
      levels associated with higher risk of acute coronary syndrome.
AB  - OBJECTIVES: It was the aim of our study to investigate whether polymorphisms of
      HSP70 have an affect on antigen and antibody levels in acute coronary syndrome
      (ACS) patients and normal controls, and the possible joint effect of variants and
      antigen and antibody levels on the risk of ACS. METHODS: Three single nucleotide
      polymorphisms of HSPA1A and HSPA1L were evaluated in 520 ACS patients and 520 age
      and sex-matched controls. Plasma extracellular Hsp70 (eHsp70) and anti-Hsp70
      antibody levels were determined using ELISA. RESULTS: Individuals with +190G/C
      (rs1043618) CC genotype in HSPA1A had higher levels of eHsp70 in controls and
      lower levels of anti-Hsp70 body in ACS, compared with +190G/C GG carriers.
      Significantly increased ACS risks of 2.93 and 3.53 fold were found in subjects
      with the +190G/C CC genotype and high eHsp70 levels or low anti-Hsp70 antibody
      levels, respectively. The highest risk of ACS was found in subjects with +190G/C
      CC genotypes, high eHsp70 and low anti-Hsp70 antibody levels compared with those
      in the reference group (OR = 7.57, 95% CI 3.04-18.87). CONCLUSIONS: The +190G/C
      polymorphism of HSPA1A may contribute to influence eHsp70 levels in controls and
      anti-Hsp70 antibody levels in ACS, and the +190G/C genotypes, eHsp70 and anti
      Hsp70 antibody levels may have a joint effect on the risk of ACS.

PMID- 21849786
TI  - Evaluation of perpendicular reflection intensity for assessment of caries lesion
      activity/inactivity.
AB  - The aim of this study was to evaluate, using visual assessment, an experimental
      optical sensor measuring perpendicular reflection intensity (PRI) as an indicator
      of enamel caries lesion activity/inactivity. Forty teeth with either an active or
      an inactive enamel lesion were selected from a pool of extracted teeth. Each
      tooth was cut into halves, with a clinically sound half and a half with a non
      cavitated enamel lesion. After gentle plaque removal, the teeth were kept
      moistened. The lesions were then photographed and a defined measuring site per
      lesion was chosen and indicated with an arrow on a printout. Independently, the
      chosen site was visually assessed for lesion activity, and its glossiness was
      measured with PRI assessment. Surface roughness (SR) was assessed with optical
      profilometry using a confocal microscope. Visual assessment and PRI were repeated
      after several weeks and a reliability analysis was performed. For enamel lesions
      visually scored as active versus inactive, significantly different values were
      obtained with both PRI and SR. PRI values of the clinically sound control
      surfaces were significantly different only from active lesions. Generally,
      inactive lesions had the same glossiness and the same roughness as the sound
      control surfaces. The reliabilities for visual assessment (kappa = 0.89) and for
      PRI (ICC = 0.86) were high. It is concluded that, within the limits of this
      study, PRI can be regarded as a promising tool for quantitative enamel lesion
      activity assessment. There is scope and potential for the PRI device to be
      considerably improved for in vivo use.

PMID- 21849785
TI  - Usefulness of red cell distribution width in predicting all-cause long-term
      mortality after non-ST-elevation myocardial infarction.
AB  - BACKGROUND: Red blood cell distribution width (RDW) is a strong predictor of
      adverse outcomes in patients with heart failure, stable coronary artery disease,
      stroke and acute myocardial infarction. The aim of our study was to explore the
      predictive value of RDW on all-cause mortality in patients with non-ST-segment
      elevation myocardial infarction (NSTEMI). METHOD: This observational study
      includes 619 NSTEMI patients, discharged from Staten Island University Hospital
      between September 2004 and December 2006. Patients were divided into equal RDW
      tertiles and survival was evaluated in each tertile. RESULT: Patients in the
      highest RDW tertile (RDW >14) had higher in-patient (7 vs. 1%) and 4-year (30 vs.
      7%) mortality rates compared to those in the lowest tertile (RDW <13) (Wilcoxon
      chi(2) = 34.64, p < 0.0001). After controlling for Global Registry of Acute
      Coronary Events risk profile scores and other confounding variables, the RDW
      adjusted hazard ratio for 4-year all-cause mortality increased by 1.10 for each
      one unit increase in RDW (confidence interval 1.004-1.213, p = 0.042).
      CONCLUSION: RDW is an independent predictor of all-cause long-term mortality in
      NSTEMI patients. Further studies are needed to clarify the mechanisms of this
      association between RDW and adverse outcomes in patients with coronary artery
      disease.

PMID- 21849787
TI  - Outcome of acute ischemic stroke in very elderly patients: is intravenous
      thrombolysis beneficial?
AB  - BACKGROUND/AIMS: Intravenous tissue plasminogen activator (tPA) treatment is
      recommended in acute stroke within 3 h of onset; however, the benefit of its use
      in the elderly remains uncertain. We assessed the safety and efficacy of tPA
      treatment in elderly patients. METHODS: We recruited 97 elderly Chinese patients
      aged >=80 years with cerebral ischemia presenting within 3 h of onset. Favorable
      outcomes were defined as discharge to home and modified Rankin Scale (mRS) <=2 at
      discharge. RESULTS: For moderate to severe patients (NIHSS >=6), the baseline
      characteristics between the tPA (n = 30) and non-tPA (n = 41) group were not
      different. The proportion of patients discharged home was 56.7 and 61%,
      respectively (p = 0.72). For patients with baseline mRS <=2, the frequency of
      discharged mRS <=2 was not different (27.3% of the tPA group and 26.9% of the non
      tPA group; p = 1.00). Symptomatic intracranial hemorrhage was 6.7 and 2.4%,
      respectively (p = 0.31). For minor stroke patients (NIHSS <=5), tPA was not
      considered and the outcome of those discharged home and mRS <=2 was 73 and 88%,
      respectively. CONCLUSION: Elderly patients can be treated safely with intravenous
      tPA, whereas our data did not support routine thrombolysis. Further randomized
      trials in the elderly are encouraged.

PMID- 21849788
TI  - Reproducibility of heart rate variability during rest, paced breathing and light
      to-moderate intense exercise in patients one month after stroke.
AB  - AIM: To examine test-retest reliability of time and frequency domain heart rate
      variability (HRV) in patients 1 month after stroke during rest, paced breathing
      and light-to-moderate physical activity. METHODS: Fifteen patients up to 1 month
      after stroke underwent two measurements of HRV, with the measurements 4 days
      apart. Measurements took place under three conditions while sitting: (1) at rest
      with self-select breathing frequency, (2) paced breathing and (3) cycling while
      sitting. Reliability was assessed statistically by calculating intraclass
      correlation coefficients (ICC), standard error of measurement and coefficient of
      variance (CV). RESULTS: The relative reliability was found to be good-to
      excellent for SDNN (ICC: 0.86-0.91), RMSSD (ICC: 0.81-0.87) and HF (ICC: 0.91
      0.94) in all three conditions and poor for LF at rest and paced breathing (ICC:
      0.43-0.47). The absolute reliability for all measures was found to be poor (CV
      >15%). CONCLUSIONS: HRV can be reliably assessed at rest, paced breathing and
      light-to-moderate physical activity for identifying differences between patients,
      while individual changes in autonomic functioning exhibited large random
      variations between test-retest measurements.

PMID- 21849789
TI  - A new approach to account for the correlations among single nucleotide
      polymorphisms in genome: wide association studies.
AB  - In genetic association studies, such as genome-wide association studies (GWAS),
      the number of single nucleotide polymorphisms (SNPs) can be as large as hundreds
      of thousands. Due to linkage disequilibrium, many SNPs are highly correlated;
      assuming they are independent is not valid. The commonly used multiple comparison
      methods, such as Bonferroni correction, are not appropriate and are too
      conservative when applied to GWAS. To overcome these limitations, many approaches
      have been proposed to estimate the so-called effective number of independent
      tests to account for the correlations among SNPs. However, many current effective
      number estimation methods are based on eigenvalues of the correlation matrix.
      When the dimension of the matrix is large, the numeric results may be unreliable
      or even unobtainable. To circumvent this obstacle and provide better estimates,
      we propose a new effective number estimation approach which is not based on the
      eigenvalues. We compare the new method with others through simulated and real
      data. The comparison results show that the proposed method has very good
      performance.

PMID- 21849790
TI  - Modifiers and subtype-specific analyses in whole-genome association studies: a
      likelihood framework.
AB  - OBJECTIVE: We propose new statistical methods for analyzing genetic case/control
      association data in which cases can be further classified into subtypes, for
      example, based on clinical features. The primary utility of our work is the
      ability to distinguish between subtype-specific and modifier effects of genetic
      variants within a single testing framework. METHODS: A range of disease/subtype
      causal models are defined for genetic variants involving subtype-specific and
      modifier effects. We present a log-linear modeling framework enabling comparison
      between these causal models and selection of the best-fit model. RESULTS: We
      evaluate and compare the analytic power and model selection performance of the
      proposed work with standard two-group-based association tests. Simulation studies
      demonstrate that our approach has similar or greater power than the traditional
      approach over a range of causal models. We also report empirical findings about
      the impact of misspecification of subtype frequency during model selection, and
      extend the application of the proposed work to the cross-disorder association
      studies of multiple diseases. CONCLUSION: Whether a variant is a disease risk
      factor, is subtype specific, or modifies disease features has important
      consequences for the interpretation and follow-up of genetic associations. Our
      framework provides a simple, systematic way to evaluate and describe associations
      involving such subtype-specific or modifier effects.

PMID- 21849791
TI  - Including additional controls from public databases improves the power of a
      genome-wide association study.
AB  - Though genome-wide association studies (GWAS) have identified numerous
      susceptibility loci for common diseases, their use is limited due to the expense
      of genotyping large cohorts of individuals. One potential solution is to use
      'additional controls', or genotype data from control individuals deposited in
      public repositories. While this approach has been used by several groups, the
      genetically heterogeneous nature of the population of the United States makes
      this approach potentially problematic. We empirically investigated the utility of
      this approach in a US-based GWAS. In a small GWAS of pancreatic cancer in New
      York, we observed clear population structure differences relative to controls
      from the database of Genotypes and Phenotypes (dbGaP). When we conduct the GWAS
      using these additional controls, we find large inflation of the test statistic
      that is properly corrected by using eigenvectors from principal components
      analysis as covariates. To deal with errors introduced due to different sources,
      we propose simultaneously genotyping a small number of controls along with cases
      and then comparing this group to the additional controls. We show that removing
      SNPs that show differences between these control groups reduces false-positive
      findings. Thus, through an empirical approach, this report provides practical
      guidance for using additional controls from publicly available datasets.

PMID- 21849792
TI  - A geographic cline of skull and brain morphology among individuals of European
      Ancestry.
AB  - BACKGROUND: Human skull and brain morphology are strongly influenced by genetic
      factors, and skull size and shape vary worldwide. However, the relationship
      between specific brain morphology and genetically-determined ancestry is largely
      unknown. METHODS: We used two independent data sets to characterize variation in
      skull and brain morphology among individuals of European ancestry. The first data
      set is a historical sample of 1,170 male skulls with 37 shape measurements drawn
      from 27 European populations. The second data set includes 626 North American
      individuals of European ancestry participating in the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) with magnetic resonance imaging, height and
      weight, neurological diagnosis, and genome-wide single nucleotide polymorphism
      (SNP) data. RESULTS: We found that both skull and brain morphological variation
      exhibit a population-genetic fingerprint among individuals of European ancestry.
      This fingerprint shows a Northwest to Southeast gradient, is independent of body
      size, and involves frontotemporal cortical regions. CONCLUSION: Our findings are
      consistent with prior evidence for gene flow in Europe due to historical
      population movements and indicate that genetic background should be considered in
      studies seeking to identify genes involved in human cortical development and
      neuropsychiatric disease.

PMID- 21849793
TI  - EX-HOM (EXome HOMozygosity): a proof of principle.
AB  - OBJECTIVE: We provide the proof of principle that exome sequencing of only two
      affected siblings born to first-cousin parents is capable of directly identifying
      a single candidate gene for an autosomal recessive disorder. This strategy, which
      we call EX-HOM (EXome HOMozygosity), combines in a single step the capacity of
      exome sequencing to identify all the coding variants present in a genome with the
      property of homozygosity mapping to limit the search for candidate genes to
      specific chromosomal regions. METHODS: We sequenced the exomes of two siblings
      born to first-cousin parents affected with dysmyelinating leukodystrophy and
      spastic paraparesis caused by a mutation in FA2H. We used exome sequencing data
      to identify homozygous regions shared by the two affected siblings (EX-HOM
      regions), compared them with the regions of maximum LOD score obtained with SNP
      genotyping, and selected the candidate variants within. RESULTS: We identified
      regions of shared homozygosity (>1 Mb) accounting for about 290 Mb, containing
      only 3 candidate variants. Among these, the FA2H mutation remained the only
      plausible one. CONCLUSION: In single consanguineous pedigrees with a few affected
      sibs, EX-HOM can be a one-step approach to identify the candidate genetic defect,
      bypassing obstacles such as genetic heterogeneity and the need for large
      pedigrees.

PMID- 21849794
TI  - Influence of thyroid function on different kidney function tests.
AB  - BACKGROUND/AIMS: The commonly used kidney function tests have limitations,
      especially in thyroid dysfunction. Therefore, we studied the most commonly used
      kidney function tests in patients with hypo- and hyperthyroidism and after
      reaching euthyroidism. METHODS: Prospective case series in 16 patients with
      thyroid dysfunction. Serum creatinine, 24-hour creatinine clearance, calculated
      glomerular filtration rate (GFR) by Cockroft-Gault, estimated GFR (eGFR) by the
      Chronic Kidney Disease Epidemiology Collaboration equation, serum cystatin C,
      eGFR based on cystatin C, eGFR based on a combined (cystatin C and creatinine)
      formula and plasma neutrophil gelatinase-associated lipocalin (NGAL) were
      measured in hypo- and hyperthyroidism and after gaining euthyroidism. RESULTS:
      When free thyroxine (fT(4)) normalized in hypothyroid patients, creatinine
      decreased and creatinine-based eGFR increased significantly. In contrast,
      cystatin C increased and eGFR based on cystatin C decreased significantly. There
      was no significant change in NGAL levels. When fT(4) normalized in patients with
      hyperthyroidism, creatinine increased and creatinine-based eGFR decreased
      significantly. In contrast, cystatin C decreased and cystatin-C-based GFR
      increased significantly. There was no significant change in NGAL levels.
      CONCLUSIONS: Thyroid function has a major influence on the vast majority of
      kidney function tests. Cystatin C is strongly influenced by the thyroid function
      and should be avoided in thyroid disorders. There was no effect on the plasma
      NGAL levels. The recommended kidney function test is a measurement of creatinine
      based eGFR.

PMID- 21849795
TI  - Hypertension as a predictive factor for survival outcomes in patients with
      metastatic renal cell carcinoma treated with sunitinib after progression on
      cytokines.
AB  - BACKGROUND/AIMS: This retrospective analysis compared progression-free survival
      (PFS) in 111 patients who developed or had preexisting hypertension with those
      who did not during treatment with second-line sunitinib. Secondary objectives
      included overall survival (OS) and safety. METHODS: Patients with metastatic
      renal cell carcinoma (mRCC) received sunitinib 50 mg orally once daily in 6-week
      cycles according to a 4-week on/2-week off treatment schedule. Treatment was
      continued until disease progression, unacceptable toxicity, withdrawal of
      consent, or death. Resting blood pressure (BP) was monitored by clinic and home
      measurements. Hypertension was defined as systolic BP >=140 and/or diastolic BP
      >=90 mm Hg. Subsequent antihypertensive treatment was empirical, depending on the
      patient. RESULTS: Fifty-four (48.6%) patients experienced elevated BP related to
      sunitinib. Of these, 10 had preexisting hypertension. Patients who developed
      hypertension related to sunitinib treatment experienced significantly longer PFS
      and OS compared to those who did not (p < 0.00001). Patients who required at
      least 3 antihypertensive drugs had the longest PFS (p = 0.00002) and OS (p =
      0.00001). CONCLUSIONS: The development of hypertension during sunitinib treatment
      was a positive predictive factor associated with a significantly longer PFS and
      OS in patients with mRCC.

PMID- 21849796
TI  - Histological diagnosis determines complications of percutaneous renal biopsy: a
      single-center experience in 353 patients.
AB  - BACKGROUND: We studied the connection between complication occurrence related to
      renal biopsies and histological diagnoses of the biopsy specimen. We also
      analyzed the distribution of diagnoses in our population. METHODS: We
      retrospectively studied 353 patients undergoing renal biopsy at the same center.
      Biopsies were performed after marking the site of puncture by ultrasound imaging.
      Connection of complications with diagnoses and clinical parameters was evaluated.
      RESULTS: Complication rate was 44.5% in our study. There was a significantly
      lower rate of complications in patients with diabetic nephropathy (likelihood
      ratio, LR = 0.44) or acute tubular necrosis (LR = 0.38), while patients with thin
      basement membrane syndrome had a more than 6-fold higher risk for development of
      intrarenal hemorrhage than others. Patients with vasculitis (LR = 2.88) and acute
      interstitial nephritis (LR = 3.18) have a more than doubled risk for
      arteriovenous shunts, while in patients with severe arteriosclerosis the
      prevalence of this complication was lower (LR = 0.46). Arteriovenous shunts
      developed also at a significantly higher rate in patients with rapidly
      progressive glomerulonephritis. CONCLUSION: Patients with thin basement membrane
      syndrome, vasculitis, rapidly progressive glomerulonephritis or acute
      interstitial nephritis should be observed more carefully after renal biopsy due
      to the significantly higher risk for certain complications.

PMID- 21849797
TI  - Anti-inflammatory effects of electroacupuncture in the respiratory system of a
      symptomatic amyotrophic lateral sclerosis animal model.
AB  - BACKGROUND: Because amyotrophic lateral sclerosis (ALS) is a progressive
      inflammatory disease, treatment of the pulmonary system plays a key role in ALS
      patients' care. Previous studies have mainly examined the pathological mechanism
      of ALS in the central nervous system; however, there has been relatively little
      research regarding the pulmonary system in ALS animal models. In inflammatory
      diseases, including asthma and arthritis, electroacupuncture (EA) is commonly
      used for its anti-inflammatory effects. The goal of this study was to determine
      whether EA treatment affects inflammation in the pulmonary system in an ALS
      animal model. METHODS: EA treatment at ST36 (Zusanli) acupoint was performed with
      14-week-old hSOD1(G93A) transgenic mice. Immunohistochemical analysis was
      performed using anti-ionized calcium binding adaptor molecule 1 (Iba-1) and anti
      tumor necrosis factor alpha (TNF-alpha) antibodies. To investigate the expression
      level of inflammatory proteins, Western blot analyses were performed using anti
      Iba-1, anti-TNF-alpha, anti-nuclear factor kappa B (NF-kappaB), and anti
      interleukin 6 (IL-6) antibodies. The activation of Ser435-phospho-specific RAC
      alpha serine/threonine-protein kinase 1 (pAKT) and the increase of phosphorylated
      extracellular-signal-regulated kinases (pERK) protein in lung tissues of EA
      treated and untreated hSOD1(G93A) mice were also evaluated by Western blot.
      RESULTS: EA treatment decreased the expression of the proinflammatory proteins
      such as TNF-alpha and IL-6, pNF-kappaB, and Iba-1 and increased the level of
      activated pAKT and pERK compared to control hSOD1(G93A) mice. CONCLUSIONS: Our
      findings suggest that EA could be an effective anti-inflammatory treatment for
      the respiratory impairment that occurs in ALS animal models.

PMID- 21849798
TI  - Traditional and nontraditional cardiovascular risk factors and estimated risk for
      coronary artery disease in renal transplant recipients: a single-center
      experience.
AB  - BACKGROUND/AIMS: The prevalence of cardiovascular disease in renal transplant
      recipients is markedly higher than in the general population due to the high
      prevalence of traditional cardiovascular risk factors, renal transplant function
      impairment and treatment with immunosuppressive drugs that affect blood pressure,
      cholesterol and blood glucose levels. METHODS: Cross-sectional analysis using our
      renal transplant clinic cohort investigating (1) the cardiovascular risk factors
      present in this cohort, and (2) estimating their impact on the risk of coronary
      artery disease (CAD) by using the Framingham algorithm. RESULTS: Control of
      modifiable cardiovascular risk factors in 231 renal transplant recipients is
      suboptimal, i.e. 47.2% of patients are hypertensive, 10.3% actively smoke, 39.4%
      have serum cholesterol concentrations >200 mg/dl, and 19.7% have diabetes
      mellitus. Blood pressure, age, hyperlipidemia, smoking and diabetes modulate the
      estimated CAD risk in males and females. Furthermore, a short time period (less
      than 1 year) since transplantation and increased serum creatinine levels
      negatively influenced the CAD risk in this patient population. CONCLUSION:
      According to current guidelines, the control of modifiable cardiovascular risk
      factors in renal transplant recipients is suboptimal. The decreasing CAD risk
      over time after transplantation may be due to the reduction of immunosuppressive
      drugs with time and survival bias.

PMID- 21849799
TI  - Genetic association studies: discovery of the genetic basis of renal disease.
AB  - Genetic association studies are a means to investigate the causal role of genes
      in diseases in order to unravel pathways involved in the etiology of disease.
      There are two types of genetic association studies: hypothesis-driven studies,
      i.e. candidate gene studies, targeting genes with a known or presumed role in
      pathways or diseases of interest, and non-hypothesis-driven studies, i.e. genome
      wide association studies, aiming for the discovery of new genetic associations.
      This educational article is an introduction to genetic association studies for
      nephrologists and researchers in the domain of kidney disease.

PMID- 21849800
TI  - Postnatal renal abnormalities in rats exposed to losartan during lactation.
AB  - BACKGROUND/AIMS: Rats exposed to losartan during lactation exhibit progressive
      changes in renal function and structure. This study analyzed the early events in
      pups from dams that received losartan during lactation. METHODS: Male Wistar rats
      from dams that received 2% sucrose (control, n = 25) or losartan (100 mg/kg/day)
      diluted in 2% sucrose (n = 33) during lactation were anesthetized 21 days after
      birth. Blood and urine samples were collected to assess renal function, and
      kidneys were removed for histological, immunohistochemical, Western blot, lipid
      peroxidation and glutathione analyses. RESULTS: The group exposed to losartan
      exhibited increased albuminuria and fractional sodium and potassium excretion,
      decreased glomerular area and interstitial expansion. Immunohistochemical
      analyses demonstrated increased tubulointerstitial macrophage infiltration,
      apoptosis and increased vimentin and alpha-smooth-muscle-actin expression in
      animals exposed to losartan. In addition, the glomeruli of animals exposed to
      losartan exhibited increased peripheral desmin expression and reduced glomerular
      epithelial protein 1 and podocin expression compared to controls. Lastly, renal
      lipid peroxidation and glutathione levels were higher in the losartan-treated
      pups. CONCLUSION: Pups exposed to losartan during lactation exhibited adverse
      changes in renal function and structure, and tubulointerstitial inflammation at
      21 days of age that were associated with apoptosis and oxidative stress.

PMID- 21849801
TI  - Monocyte- and endothelial-derived microparticles induce an inflammatory phenotype
      in human podocytes.
AB  - BACKGROUND/AIMS: Proteinuria is associated with cardiovascular and chronic kidney
      disease. Microparticles (MPs) are bioactive vesicles shed from activated cells
      and also linked to cardiovascular disease. MP-like structures have been
      identified in the glomerular basement membrane, urinary space and between the
      glomerular basement membrane and the podocyte. We hypothesised that circulating
      MPs may provide a link between vascular injury and kidney diseases by inducing
      podocyte phenotypic alterations, thus propagating glomerular dysfunction and
      proteinuria. METHODS: Human umbilical vein endothelial cells and U937 monocytes
      were stimulated with TNF-alpha to produce MPs. These MPs were confirmed by
      electron microscopy, and added to differentiated podocyte monolayers to determine
      effects on podocyte albumin endocytosis and the production of soluble mediators.
      RESULTS: Monocyte and endothelial MPs upregulated podocyte production of pro
      inflammatory mediators monocyte chemoattractant protein-1 (p < 0.001) and
      interleukin-6 (p < 0.001). Only monocyte MPs upregulated podocyte secretion of
      VEGF (p < 0.001), known to regulate glomerular permeability. Endothelial MPs
      decreased podocyte albumin endocytosis by 13% compared to control cells (p <
      0.01). CONCLUSION: MPs alter endocytic functions of podocytes and induce
      secretion of pro-inflammatory cytokines, potentially leading to glomerular
      inflammation in vivo and the development of proteinuria. This study identifies a
      potential pathophysiological role for circulating MPs in the kidney through
      effects on the podocyte.

PMID- 21849802
TI  - Differential effects of oral doxercalciferol (Hectorol) or paricalcitol (Zemplar)
      in the Cyp27b1-null mouse model of uremia.
AB  - BACKGROUND/AIMS: Kidney disease patients experience declining calcitriol levels
      and develop secondary hyperparathyroidism (SHPT). Animal models of uremia based
      on 5/6 nephrectomy (NTX) do not consistently reproduce this calcitriol
      deficiency. We developed an animal model, the NTX Cyp27b1-null mouse, which
      completely lacks endogenous calcitriol, and examined the suitability of this
      model for evaluation of treatment with vitamin D analogs in uremia. METHODS: NTX
      was performed at 2 months of age. One week post-NTX, animals were treated for 4
      weeks with vehicle; doxercalciferol at 30, 100 or 300 pg/g body weight (b.w.); or
      paricalcitol at 100, 300 or 1,000 pg/g b.w. by gavage 3 times per week. RESULTS:
      Serum blood urea nitrogen and creatinine were elevated. Vehicle-treated NTX null
      mice had hypocalcemia and SHPT. Doxercalciferol at 100 or 300 pg/g b.w.
      normalized serum calcium and parathyroid hormone (PTH) levels. Paricalcitol at
      300 or 1,000 pg/g normalized serum calcium, but PTH levels remained elevated.
      Osteomalacia was corrected by 100 pg/g b.w. of doxercalciferol or 1,000 pg/g b.w.
      of paricalcitol. The highest dose of doxercalciferol, but not of paricalcitol,
      significantly reduced osteitis fibrosa. CONCLUSION: Our results reveal the
      differential efficacy of doxercalciferol and paricalcitol in this novel animal
      model incorporating both calcitriol deficiency and renal insufficiency.

PMID- 21849803
TI  - Familial autosomal recessive renal tubular acidosis: importance of early
      diagnosis.
AB  - BACKGROUND AND AIMS: Untreated renal tubular acidosis (RTA) can result in severe
      complications. We reviewed the clinical features of patients with mutations in
      two genes causing RTA and evaluated their developmental expression assuming that
      timing, symptom severity and complications may be related to its occurrence.
      METHODS: Clinical data from 16 patients with RTA due to mutations in either
      ATP6V1B1 or CAII were retrospectively reviewed. Both genes' localization and
      expression pattern in the developing human kidney were analyzed by real-time
      polymerase chain reaction and immunostaining. RESULTS: RTA-presenting symptoms
      were non-specific. Patients with mutations in ATP6V1B1 had earlier presentation
      (4.9 vs. 11 months, p < 0.041) and longer time to diagnosis than patients with
      CAII mutations (5.8 vs. 57 months, p < 0.01). Patients with ATP6V1B1 mutations
      were more likely to develop chronic kidney disease than those with CAII mutations
      (follow-up GFR values: 89 vs. 110 ml/min/1.73 m2, respectively, p < 0.017),
      probably secondary to nephrocalcinosis. Both ATP6V1B1 and CAII were expressed
      early during human nephrogenesis, with relatively higher transcript levels of
      ATP6V1B1. CONCLUSIONS: There is considerable delay in establishing a diagnosis of
      both types of RTA, supporting the need for earlier biochemical investigation. RTA
      due to ATP6V1B1 mutations is associated with mild progressive loss of kidney
      function.

PMID- 21849804
TI  - KCNJ10 mutations disrupt function in patients with EAST syndrome.
AB  - BACKGROUND/AIMS: Mutations in the inwardly-rectifying K+ channel KCNJ10/Kir4.1
      cause an autosomal recessive disorder characterized by epilepsy, ataxia,
      sensorineural deafness and tubulopathy (EAST syndrome). KCNJ10 is expressed in
      the kidney distal convoluted tubule, cochlear stria vascularis and brain glial
      cells. Patients clinically diagnosed with EAST syndrome were genotyped to
      identify and study mutations in KCNJ10. METHODS: Patient DNA was sequenced and
      new mutations identified. Mutant and wild-type KCNJ10 constructs were cloned and
      heterologously expressed in Xenopus oocytes. Whole-cell K+ currents were measured
      by two-electrode voltage clamping. RESULTS: Three new mutations in KCNJ10
      (p.R65C, p.F75L and p.V259fs259X) were identified, and mutation p.R297C,
      previously only seen in a compound heterozygous patient, was found in a
      homozygous state. Wild-type human KCNJ10-expressing oocytes showed strongly
      inwardly-rectified currents, which by comparison were significantly reduced in
      all the mutants (p < 0.001). Specific inhibition of KCNJ10 currents by Ba2+
      demonstrated residual function in all mutant channels (p < 0.05) but V259X.
      CONCLUSION: This study confirms that EAST syndrome can be caused by many
      different mutations in KCNJ10 that significantly reduce K+ conductance. EAST
      syndrome should be considered in any patient with a renal Gitelman-like phenotype
      with additional neurological signs and symptoms like ataxia, epilepsy or
      sensorineural deafness.

PMID- 21849805
TI  - Matrix metalloproteinase-13 promotes recovery from experimental liver cirrhosis
      in rats.
AB  - OBJECTIVE: To evaluate the role of matrix metalloproteinase (MMP)-13 gene
      expression in the early phase of recovery from liver fibrosis/cirrhosis. METHODS:
      Liver fibrosis was induced in male Wistar rats by administration of carbon
      tetrachloride (CCl(4)) for 10 weeks. Recombinant adenovirus-mediated human MMP-13
      gene transfer (RAdMMP-13) was performed via the femoral vein on day 3 after the
      last CCl(4) injection. The role of MMP-13 in stably expressing cell lines was
      also analyzed. RESULTS: Fibrous deposition in the liver was decreased in RAdMMP
      13-injected rats by day 3 after gene transfer compared with empty vector RAd66
      injected rats. Furthermore, MMP-2 and MMP-9 enzymatic activity was markedly
      enhanced in the liver of RAdMMP-13 injected rats. Hepatocyte growth factor (HGF)
      induction was also increased in RAdMMP-13 injected rats. In established stable HT
      1080 cells transfected with MMP-13, HGF-alpha expression and MMP-2 and MMP-9
      enzymatic activity were increased. The conversion of precursor HGF into mature
      HGF was also increased in the MMP-13 expressing cell lines. CONCLUSION: Forced
      MMP-13 expression effectively accelerated recovery from liver cirrhosis via the
      effects of MMP-13-mediated HGF, MMP-2, and MMP-9 expression, which induced the
      degradation of collagen fibers and promoted hepatic regeneration.

PMID- 21849806
TI  - Platelet-derived growth factor regulates breast cancer progression via beta
      catenin expression.
AB  - OBJECTIVE: The knowledge on the association between platelet-derived growth
      factor (PDGF) signaling and epithelial cancers is scarce, although overexpression
      of PDGF and PDGF receptors has been reported in some human mesenchymal tumors.
      Thus, we studied the effect of PDGF on breast cancer cells in vitro and the
      distribution of PDGF in breast cancer tissues. METHODS: The effect of PDGF-BB on
      breast cancer cells was assessed by Western blotting, immunofluorescence, WST and
      5-bromo-2-deoxyuridine incorporation experiments. PDGF-B and beta-catenin
      expression was investigated in breast cancer tissues by immunohistochemistry.
      RESULTS: PDGF-BB induces beta-catenin expression in breast cancer cells, and
      immunohistochemically the distribution of PDGF-B was similar to beta-catenin in
      breast cancer cells. PDGF-B-positive cancer cells were more frequent in cases of
      ductal carcinoma in situ (87.5%) than invasive carcinoma (61.2%). In addition,
      PDGF-B staining was stronger in intraductal than invasive cancer cells. PDGF-BB
      tended to induce nuclear translocation of beta-catenin, cell proliferation and
      DNA incorporation in MDA-MB231 cells, while these results were not found in MCF-7
      cells. CONCLUSION: Our results suggest that PDGF-BB regulates protein expression
      of beta-catenin and is associated with cancer cell behavior.

PMID- 21849807
TI  - Elevated tumor necrosis factor in serum is associated with increased retinal
      ischemia in proliferative eales' disease.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) was evaluated in the serum of patients
      with proliferative stage of Eales' disease to study its relation with the area of
      retinal capillary non-perfusion (ischemic retina). METHODS: Quantification of the
      levels of TNF was done using sandwich ELISA in 52 cases with proliferative Eales'
      disease and in 32 healthy controls. Seven 50 degrees  photographs of different
      fields of the fundus were taken on fluorescein angiography. The area of retinal
      capillary non-perfusion denoting retinal cell death was assessed in terms of
      optic disc areas. RESULTS: TNF levels were found to be significantly increased in
      the proliferative stage of the disease (mean 23.64 +/- 3.7 pg/ml) as compared to
      controls (mean 12.49 +/- 2.9 pg/ml; p < 0.001). Higher levels of TNF were found
      to be associated with an increased area of retinal capillary non-perfusion on
      fluorescein angiography. TNF levels of 20-31 pg/ml were observed in cases with
      neovascularization at the disc (n = 33) as compared to 17-21 pg/ml in cases with
      neovascularization elsewhere (n = 19). CONCLUSIONS: An increased level of TNF is
      associated with an increased area of the ischemic retina. It is hypothesized that
      retinal cell death signaling in proliferative Eales' disease is related to an
      increased TNF level.

PMID- 21849808
TI  - Inactivation of COX-2, HMLH1 and CDKN2A gene by promoter methylation in gastric
      cancer: relationship with histological subtype, tumor location and Helicobacter
      pylori genotype.
AB  - OBJECTIVE: We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by
      promoter methylation and its relationship with the infection by different
      Helicobacter pylori strains in gastric cancer. METHODS: DNA extracted from 76 H.
      pylori-positive gastric tumor samples was available for promoter methylation
      identification by methylation-specific PCR and H. pylori subtyping by PCR.
      Immunohistochemistry was used to determine COX-2, p16(INK4A) and HMLH1
      expression. RESULTS: A strong negative correlation was found between the
      expression of these markers and the presence of promoter methylation in their
      genes. Among cardia tumors, negativity of p16(INK4A) was a significant finding.
      On the other hand, in noncardia tumors, the histological subtypes had different
      gene expression patterns. In the intestinal subtype, a significant finding was
      HMLH1 inactivation by methylation, while in the diffuse subtype, CDKN2A
      inactivation by methylation was the significant finding. Tumors with methylated
      COX-2 and HMLH1 genes were associated with H. pylori vacA s1 (p = 0.025 and
      0.047, respectively), and the nonmethylated tumors were associated with the
      presence of the gene flaA. CONCLUSIONS: These data suggest that the inactivation
      of these genes by methylation occurs by distinct pathways according to the
      histological subtype and tumor location and depends on the H. pylori genotype.

PMID- 21849809
TI  - Identification of transmembrane protein in prostate cancer by the Escherichia
      coli ampicillin secretion trap: expression of CDON is involved in tumor cell
      growth and invasion.
AB  - AIMS: Prostate cancer (PCa) is one of the most common malignancies worldwide.
      Genes expressed only in cancer tissue, and especially related to proteins located
      on the cell membrane, will be useful molecular markers for diagnosis and may also
      be good therapeutic targets. The aim of this study was to identify genes that
      encode transmembrane proteins present in PCa. METHODS AND RESULTS: We generated
      Escherichia coli ampicillin secretion trap (CAST) libraries from 2 PCa cell lines
      and normal prostate tissues. By sequencing 3,264 colonies from CAST libraries, we
      identified 18 candidate genes that encode transmembrane proteins present in PCa.
      Quantitative RT-PCR analysis of these candidates revealed that STEAP1, ADAM9 and
      CDON were expressed much more highly in PCa than in 15 kinds of normal tissues.
      Among the candidates, CDON encodes the CDO protein, which is an orphan cell
      surface receptor of the immunoglobulin superfamily. Additional quantitative RT
      PCR revealed that 83% of PCa tissues showed CDON overexpression. Knockdown of
      CDON in DU145 cells induced 5-fluorouracil-induced apoptosis and inhibited
      invasion ability. CONCLUSION: These results suggest that CDON has a high
      potential as a therapeutic target for PCa.

PMID- 21849810
TI  - Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon
      cancer cells.
AB  - The effect of diabetic conditions on liver metastasis was examined using CT26
      mouse colon cancer cells. CT26 cells produced angiotensin (A)-I and A-II from
      angiotensinogen; the production was abrogated by inhibitors of renin and chymase.
      Renin expression and A-II production increased with an increase in the
      concentration of glucose in the medium. In a streptozotocin-induced BALB/c mouse
      diabetes model that was fed a high-calorie diet, the blood sugar level increased
      and was associated with an increasing size and number of CT26 liver metastases.
      In this diabetic mouse model, liver metastasis of CT26 cells was suppressed by
      anti-angiotensin treatment with a chymase inhibitor, a renin inhibitor, and an A
      II receptor blocker. Moreover, concurrent hypoglycemic and anti-angiotensin
      treatments showed a synergistic inhibitory effect on CT26 cell liver metastasis.
      These results suggest that angiotensin activation ability associated with
      diabetic conditions enhances liver metastasis of colon cancer. Therefore,
      treatment with anti-angiotensin and hypoglycemic agents might be relevant for
      baseline management of colon cancer patients with the diabetic condition for the
      prevention of liver metastasis. This scheme needs to be examined in a clinical
      setting.

PMID- 21849811
TI  - Assessment of hippocampal adeno-associated viral vector gene delivery via
      frameless stereotaxis in a nonhuman primate.
AB  - BACKGROUND/AIMS: Expression of the neuropeptide galanin in hippocampal neurons
      reduces seizures in the kainic acid rodent model of epilepsy. In order to
      translate these findings into a human clinical trial, the safety and feasibility
      of hippocampal adeno-associated viral (AAV) vector expression must be
      demonstrated in a nonhuman primate model. METHODS: The Stealth Frameless
      Stereotactic System and Navigus Biopsy Appliance (Medtronic) were used to inject
      self-complementary AAV2 carrying the gene for green fluorescent protein (GFP)
      into monkey hippocampi. Using a single occipital trajectory per side (n = 8
      trajectories), multiple injections spaced by 5 mm were delivered to each
      hippocampus. RESULTS: GFP was expressed in both neuronal and glial cells.
      Injections led to nonhomogeneous gene expression, suggesting closer spacing of
      injections may lead to more gene expression. Increasing injection volumes
      entailed a general increase in volume of expression, but there was no overlap of
      expression within the 5-mm injection interval. Efforts to avoid the occipital
      horn failed to prevent leaking of vector into the ventricle, and resulted in
      deviation of the trajectory at proximal points from the hippocampus. CONCLUSION:
      Using the occipital approach, adequate cannulation of the monkey hippocampus will
      require transventricular trajectories.

PMID- 21849812
TI  - The mamillothalamic tract is a good landmark for the anterior border of the
      subthalamic nucleus on axial MR images.
AB  - BACKGROUND: Identification of the subthalamic nucleus (STN) on MR images is
      difficult, and the use of external landmarks could be of interest for STN
      targeting in deep brain stimulation (DBS). OBJECTIVES: Our aim was to explore the
      relationship between the anteroposterior coordinates of (1) the center of the
      mamillothalamic tract and (2) the anterior border of the STN on axial MR images.
      PATIENTS AND METHODS: The brains of 16 healthy volunteers were imaged on a 3T MR
      system. Four millimeters under the anterior-posterior commissure plane, we noted
      the y coordinates of (1) the center of the mamillothalamic tract and (2) the
      anterior border of the STN. RESULTS: The coordinates were y(STN) = 14.7 +/- 1.23
      mm and y(Tmth) = 14.3 +/- 1.13 mm from the posterior commissure for the STN and
      the mamillothalamic tract, respectively. The mean difference was 0.4 mm (range 0
      1 mm). Pearson's coefficient was 0.97 (p < 0.01). CONCLUSION: We observed a
      strong correlation between the anteroposterior coordinates of the mamillothalamic
      tract and the anterior border of the STN (which is located between 0 and 1 mm in
      front of the mamillothalamic tract). The mamillothalamic tract could be a good
      anterior landmark for STN targeting. It could also be tested for target
      determination in DBS for severe obsessive-compulsive disorder.

PMID- 21849813
TI  - Gamma knife radiosurgery for glomus jugulare and tympanicum.
AB  - OBJECTIVE: To establish the role of gamma knife radiosurgery (GKS) as a treatment
      strategy for glomus jugulare and tympanicum. METHOD: A retrospective review of 14
      glomus tumors, including 11 glomus jugulare and 3 glomus tympanicum tumors, which
      were treated by GKS in Taipei Veterans General Hospital from 1993 to 2009, was
      conducted. Two of these cases had undergone prior surgery with partial tumor
      resection, and the other 12 cases received primary treatment with GKS after a
      thorough neuroimaging and cerebral angiography. The tumor volume ranged from 6.5
      to 22.1 ml. The maximum dose at the tumor center ranged from 21.6 to 26.3 Gy. All
      14 patients were regularly followed up by clinical and radiological evaluations.
      The median follow-up time was 40.3 months. RESULTS: All 14 patients had
      significant tumor regression after radiosurgery. The median tumor volume
      reduction was 34.0% (range 3-79%). Only 1 patient had temporary tumor volume
      progression (24% increment 6 months post-treatment), accompanied with unilateral
      facial palsy (from grade III to grade IV) and hearing impairment (from grade I to
      grade II). The tumor volume of this patient had regressed by 12 months, but
      facial palsy persisted. The tumor control rate in the series was 100% (n =
      14/14), and the preservation rate of cranial nerve function was 92.8% (13/14).
      There was no complication of lower cranial nerve damage after radiosurgery.
      CONCLUSION: GKS appeared to be a good alternative or adjuvant to microsurgical
      resection in patients who are not amenable to complete surgical eradication, with
      an excellent tumor control rate and little morbidity after long-term follow-up.

PMID- 21849814
TI  - Probe depth matters in dermal microdialysis sampling of benzoic acid after
      topical application: an ex vivo study in human skin.
AB  - Microdialysis (MD) in the skin - dermal microdialysis (DMD) - is a unique
      technique for sampling of topically as well as systemically administered drugs at
      the site of action, e.g. sampling of dermatological drug concentrations in the
      dermis. Debate has concerned the existence of a correlation between the depth of
      the sampling device - the probe - in the dermis and the amount of drug sampled
      following topical drug administration. This study evaluates the relation between
      probe depth and drug sampling using dermal DMD sampling ex vivo in human skin. We
      used superficial (<1 mm), intermediate (1-2 mm) and deep (>2 mm) positioning of
      the linear MD probe in the dermis of human abdominal skin, followed by topical
      application of 4 mg/ml of benzoic acid (BA) in skin chambers overlying the
      probes. Dialysate was sampled every hour for 12 h and analysed for BA content by
      high-performance liquid chromatography. Probe depth was measured by 20-MHz
      ultrasound scanning. The area under the time-versus-concentration curve (AUC)
      describes the drug exposure in the tissue during the experiment and is a relevant
      parameter to compare for the 3 dermal probe depths investigated. The AUC(0-12)
      were: superficial probes: 3,335 +/- 1,094 MUg.h/ml (mean +/- SD); intermediate
      probes: 2,178 +/- 1,068 MUg.h/ml, and deep probes: 1,159 +/- 306 MUg.h/ml. AUC(0
      12) sampled by the superficial probes was significantly higher than that of
      samples from the intermediate and deeply positioned probes (p value <0.05). There
      was a significant inverse correlation between probe depth and AUC(0-12) sampled
      by the same probe (p value <0.001, r(2) value = 0.5). The mean extrapolated lag
      times (+/-SD) for the superficial probes were 0.8 +/- 0.1 h, for the intermediate
      probes 1.7 +/- 0.5 h, and for the deep probes 2.7 +/- 0.5 h, which were all
      significantly different from each other (p value <0.05). In conclusion, this
      paper demonstrates that there is an inverse relationship between the depth of the
      probe in the dermis and the amount of drug sampled following topical penetration
      ex vivo. The result is of relevance to the in vivo situation, and it can be
      predicted that the differences in sampling at different probe depths will have a
      more significant impact in the beginning of a study or in studies of short
      duration. Based on this study it can be recommended that studies of topical drug
      penetration using DMD sampling should include measurements of probe depth and
      that efforts should be made to minimize probe depth variability.

PMID- 21849815
TI  - Jasmonate signal induced expression of cystatin genes for providing resistance
      against Karnal bunt in wheat.
AB  - Two wheat varieties HD-29 (resistant, R) and WH-542 (susceptible, S) were
      pretreated with jasmonic acid (JA) or jasmonate and then artificially inoculated
      with sporidial suspension of Tilletia indica to study its influence in reducing
      Karnal bunt (KB) infection by regulating cystatin gene expression. JA was found
      to improve the plant defense against KB as its exogenous application resulted in
      decrease in coefficient of infection (CI) in both susceptible and resistant
      varieties following pathogen inoculation. Transcript profiling of wheat cystatin
      genes at different days after inoculation (DAI) showed that JA pretreatment
      positively induced cystatin gene expression in both varieties with greater
      induction of expression in resistant variety than the susceptible one (P< 0.05).
      Different temporal expression of three wheat cystatin genes, WC2, WC3 and WCMD
      was observed with their increased expression at 1DAI in the boot emergence stage
      which is most susceptible to KB and then slowly declined gradually at 3, 7 and 15
      DAI in both the varieties. Except WC2, higher expression of other two cystatins
      viz. WC3 and WCMD at 1DAI showed higher response (P< 0.05) to KB pathogenesis at
      the disease-prone boot emergence stage as also evident by decrease of CI in both
      varieties. The results of determination of specific activity of cystatin by
      inhibitor assay were found to be consistent with those of transcript profiling.
      These findings suggest that jasmonic acid (JA) may act as a potential activator
      of induced resistance against Karnal bunt of wheat by upregulating cystatin gene
      expression.

PMID- 21849816
TI  - AtAGP18, a lysine-rich arabinogalactan protein in Arabidopsis thaliana, functions
      in plant growth and development as a putative co-receptor for signal
      transduction.
AB  - Arabinogalactan-proteins (AGPs) are a class of hyperglycosylated, hydroxyproline
      rich glycoproteins that are widely distributed in the plant kingdom. AtAGP17, 18
      and 19 are homologous genes encoding three classical lysine-rich AGPs in
      Arabidopsis. We observed subcellular localization of AtAGP18 at the plasma
      membrane by expressing a translational fusion gene construction of AtAGP18
      attached to a green fluorescent protein (GFP) tag in Arabidopsis plants. We also
      overexpressed AtAGP18 without the GFP tag in Arabidopsis plants, and the
      resulting transgenic plants had a short, bushy phenotype. Here we discuss
      putative roles of AtAGP18 as a glycosylphosphatidylinositol (GPI)-anchored
      protein involved in a signal transduction pathway regulating plant growth and
      development.

PMID- 21849817
TI  - Creating drought- and salt-tolerant cotton by overexpressing a vacuolar
      pyrophosphatase gene.
AB  - Increased expression of an Arabidopsis vacuolar pyrophosphatase gene, AVP1, leads
      to increased drought and salt tolerance in transgenic plants, which has been
      demonstrated in laboratory and field conditions. The molecular mechanism of AVP1
      mediated drought resistance is likely due to increased proton pump activity of
      the vacuolar pyrophosphatase, which generates a higher proton electrochemical
      gradient across the vacuolar membrane, leading to lower water potential in the
      plant vacuole and higher secondary transporter activities that prevent ion
      accumulation to toxic levels in the cytoplasm. Additionally, overexpression of
      AVP1 appears to stimulate auxin polar transport, which in turn stimulates root
      development. The larger root system allows AVP1-overexpressing plants to absorb
      water more efficiently under drought and saline conditions, resulting in stress
      tolerance and increased yields. Multi-year field-trial data indicate that
      overexpression of AVP1 in cotton leads to at least 20% more fiber yield than wild
      type control plants in dry-land conditions, which highlights the potential use of
      AVP1 in improving drought tolerance in crops in arid and semiarid areas of the
      world. 

PMID- 21849818
TI  - Water deficit as a regulatory switch for legume root responses.
AB  - Plant roots perceive declining soil water potential as an initial signal which
      further triggers an array of physiological, morphological and molecular responses
      in the whole plant. Understanding the root responses with parallel insights on
      protein level changes has always been an area of interest for stress biologists.
      In a recent study, we reported drought stress-induced changes among certain
      structural and functional root proteins involved in reactive oxygen species (ROS)
      detoxification, primary and secondary metabolite biosynthetic pathways as well as
      proteins associated with cell signalling in an economically important legume crop
      Vigna radiata (L.) Wilczek. We also demonstrated photosynthetic gas exchange
      characteristics and root physiology under varying levels of water-deficit and
      recovery. In this report, we depict a closer analysis of the expression patterns
      of the identified proteins which were categorized into five major functional
      groups. These proteins represent a unique coherence and networking with each
      other as well as with the overall physiological and metabolic machinery in the
      plant cell.

PMID- 21849819
TI  - Transportsomes and channelsomes: are they functional units for physiological
      responses?
AB  - Channels and transporters play essential biological roles primarily through the
      transportation of ions and small molecules that are required to maintain cellular
      activities across the biomembrane. Secondary to transportation, channels and
      transporters also integrate and coordinate biological functions at different
      levels, ranging from the subcellular (nm) to multicellular (MUm) scales. This is
      underpinned by efficient functional coupling within molecular assemblies of
      channels, transporters, proteins, small molecules, and lipids. Molecular
      interactions create local microenvironments that, in some cases, uniquely modify
      the functional properties of the channels and transporters. These molecular
      assemblies built around a transporter or channel ("transportsomes" and
      "channelsomes") can be considered as physiological functional units. In this
      special issue, we provide an overview of recent progress in our understanding of
      protein-protein and molecular interactions in transportsomes and channelsomes,
      which occur through both direct molecular contacts and more distal functional
      coupling, and examine the validity of these "somes".

PMID- 21849820
TI  - Noise analysis to study unitary properties of transporter-associated ion
      channels.
AB  - Excitatory amino acid transporters (EAATs) do not only mediate secondary-active
      glutamate uptake but also function as anion channels. We recently used
      macroscopic current recordings and noise analysis to determine unitary current
      amplitudes of anion channels associated with a neuronal EAAT isoform, EAAT4. We
      found that, at symmetrical NO(3)(-), EAAT4 anion channels exhibit a single
      channel conductance of ~1 pS in the absence as well as in the presence of
      glutamate. These results indicate that glutamate increases EAAT4 anion currents
      by modifying exclusively open probabilities, however, leaves unitary current
      amplitudes unaffected. Noise analysis has been developed for ion channels with a
      single conductance state and limitations might ensue when using this approach for
      transporter-associated ion channels. We here performed stochastic simulations of
      EAAT transporter-associated anion channels and noise analysis of simulated
      currents to assess the reliability and possible limitations of this technique in
      studying this special class of ion channels.

PMID- 21849821
TI  - Influence of Alzheimer disease family history and genetic risk on cognitive
      performance in healthy middle-aged and older people.
AB  - OBJECTIVES: Identification of risk factors for Alzheimer disease (AD) is critical
      for establishing effective diagnostic and therapeutic strategies. Carrying the
      epsilon4 allele of the apolipoprotein E gene (APOE4) and having a family history
      of the disease are two such factors, with family history risk reflecting
      additional yet unknown or rarely studied genetic and perhaps nongenetic risks.
      Our aim was to determine the influence of APOE genotype and family history status
      on cognitive performance in healthy individuals. DESIGN: Longitudinal study.
      SETTING: Semel Institute for Neuroscience and Human Behavior, University of
      California, Los Angeles. PARTICIPANTS: Seventy-two cognitively healthy middle
      aged and older people (mean age +/- SD: 62 +/- 9 years). MEASUREMENTS:
      Neuropsychological examinations at baseline and after 2 years. RESULTS: Subjects
      with a family history of AD had lower baseline scores in processing speed,
      executive functioning, memory encoding, and delayed memory when compared with
      those without a family history. The family history risk factor did not influence
      degree of cognitive decline over time. By contrast, baseline cognitive
      performance did not vary according to APOE4 carrier status. Non-APOE4 carriers
      showed improved cognitive performance in the memory domains at follow-up, while
      performance of APOE4 carriers did not change. CONCLUSIONS: Our data highlight the
      unique contributions of each risk factor to cognitive performance in healthy
      people. Both factors should be modeled in neuropsychological assessments of
      people at risk for AD.

PMID- 21849823
TI  - Guidelines for the determination of brain death in infants and children: an
      update of the 1987 Task Force recommendations.
AB  - OBJECTIVE: To review and revise the 1987 pediatric brain death guidelines.
      METHODS: Relevant literature was reviewed. Recommendations were developed using
      the Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      system. CONCLUSIONS AND RECOMMENDATIONS: 1) Determination of brain death in term
      newborns, infants, and children is a clinical diagnosis based on the absence of
      neurologic function with a known irreversible cause of coma. Because of
      insufficient data in the literature, recommendations for preterm infants <37 wks
      gestational age are not included in this guideline. 2) Hypotension, hypothermia,
      and metabolic disturbances should be treated and corrected and medications that
      can interfere with the neurologic examination and apnea testing should be
      discontinued allowing for adequate clearance before proceeding with these
      evaluations. 3) Two examinations, including apnea testing with each examination
      separated by an observation period, are required. Examinations should be
      performed by different attending physicians. Apnea testing may be performed by
      the same physician. An observation period of 24 hrs for term newborns (37 wks
      gestational age) to 30 days of age and 12 hrs for infants and children (>30 days
      to 18 yrs) is recommended. The first examination determines the child has met the
      accepted neurologic examination criteria for brain death. The second examination
      confirms brain death based on an unchanged and irreversible condition. Assessment
      of neurologic function after cardiopulmonary resuscitation or other severe acute
      brain injuries should be deferred for >=24 hrs if there are concerns or
      inconsistencies in the examination. 4) Apnea testing to support the diagnosis of
      brain death must be performed safely and requires documentation of an arterial
      Paco2 20 mm Hg above the baseline and >=60 mm Hg with no respiratory effort
      during the testing period. If the apnea test cannot be safely completed, an
      ancillary study should be performed. 5) Ancillary studies (electroencephalogram
      and radionuclide cerebral blood flow) are not required to establish brain death
      and are not a substitute for the neurologic examination. Ancillary studies may be
      used to assist the clinician in making the diagnosis of brain death a) when
      components of the examination or apnea testing cannot be completed safely as a
      result of the underlying medical condition of the patient; b) if there is
      uncertainty about the results of the neurologic examination; c) if a medication
      effect may be present; or d) to reduce the interexamination observation period.
      When ancillary studies are used, a second clinical examination and apnea test
      should be performed and components that can be completed must remain consistent
      with brain death. In this instance, the observation interval may be shortened and
      the second neurologic examination and apnea test (or all components that are able
      to be completed safely) can be performed at any time thereafter. 6) Death is
      declared when these criteria are fulfilled.

PMID- 21849824
TI  - Towards changing the definition of the acute respiratory distress syndrome: one
      step forward.

PMID- 21849822
TI  - Agreement in electrocardiogram interpretation in patients with septic shock.
AB  - OBJECTIVE: The reliability of electrocardiogram interpretation to diagnose
      myocardial ischemia in critically ill patients is unclear. In adults with septic
      shock, we assessed intra- and inter-rater agreement of electrocardiogram
      interpretation, and the effect of knowledge of troponin values on these
      interpretations. DESIGN: Prospective substudy of a randomized trial of
      vasopressin vs. norepinephrine in septic shock. SETTING: Nine Canadian intensive
      care units. PATIENTS: Adults with septic shock requiring at least 5 MUg/min of
      norepinephrine for 6 hrs. INTERVENTIONS: Twelve-lead electrocardiograms were
      recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug
      initiation. MEASUREMENTS: Two physician readers, blinded to patient data and
      group, independently interpreted electrocardiograms on three occasions (first two
      readings were blinded to patient data; third reading was unblinded to troponin).
      To calibrate and refine definitions, both readers initially reviewed 25 trial
      electrocardiograms representing normal to abnormal. Cohen's Kappa and the phi
      statistic were used to analyze intra- and inter-rater agreement. RESULTS: One
      hundred twenty-one patients (62.2 +/- 16.5 yrs, Acute Physiology and Chronic
      Health Evaluation II 28.6 +/- 7.7) had 373 electrocardiograms. Blinded to
      troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as
      normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was
      moderate for overall ischemia (kappa 0.54 and 0.58), moderate/good for "normal"
      (kappa 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation,
      T inversion, and Q waves, reader 1 kappa 0.40 to 0.69; reader 2 kappa 0.56 to
      0.70); and good/very good for atrial arrhythmias (kappa 0.84 and 0.79) and bundle
      branch block (kappa 0.88 and 0.79). Inter-rater agreement was fair for ischemia
      (kappa 0.29), moderate for ST elevation (kappa 0.48), T inversion (kappa 0.52),
      and Q waves (kappa 0.44), good for bundle branch block (kappa 0.78), and very
      good for atrial arrhythmias (kappa 0.83). Inter-rater agreement for ischemia
      improved from fair to moderate (kappa 0.52, p = .028) when unblinded to troponin.
      CONCLUSIONS: In patients with septic shock, inter-rater agreement of
      electrocardiogram interpretation for myocardial ischemia was fair, and improved
      with troponin knowledge.

PMID- 21849825
TI  - Burn fluid resuscitation: let the autopilot do it!

PMID- 21849826
TI  - Acute kidney injury: clear the kidney of apoptotic debris!

PMID- 21849827
TI  - Too much of a good thing is not necessarily better.

PMID- 21849828
TI  - Take a deep breath....

PMID- 21849829
TI  - Antibiotics in sepsis: Timing, appropriateness, and (of course) timely
      recognition of appropriateness.

PMID- 21849830
TI  - Myocardial infarction complicated by cardiogenic shock: a possible role for the
      Impella device?

PMID- 21849831
TI  - Electrocardiogram interpretation for ischemia in patients with septic shock: a
      disheartening exercise.

PMID- 21849832
TI  - Danger at the doorstep: regulation of bacterial translocation across the
      intestinal barrier by nitric oxide.

PMID- 21849833
TI  - Beneficial effects of carbamylated erythropoeitin on trauma-induced brain edema:
      proposed molecular mechanisms of action.

PMID- 21849834
TI  - Globalization of ejection fraction: the pulmonary artery catheter has been
      outsourced.

PMID- 21849835
TI  - Pseudomonas aeruginosa: so many virulence factors, so little time.

PMID- 21849836
TI  - How alcohol impairs the granulocyte expansion during septicemia.

PMID- 21849837
TI  - Plumbing the depths of blood pressure: hypotensive hemorrhage and acute kidney
      injury.

PMID- 21849838
TI  - Pediatric brain death.

PMID- 21849839
TI  - Opening our eyes to postoperative pulmonary complications.

PMID- 21849840
TI  - Just fastening the belt! Is it the future measure for assessing fluid
      responsiveness?

PMID- 21849841
TI  - Web-based resources for critical care education. The EVIDENCE Crash Course: a Web
      based interactive e-course on infection prevention for critical care clinicians.

PMID- 21849842
TI  - Proxy evaluation of quality of life in elderly patients.

PMID- 21849843
TI  - Angiopoietins as prognostic biomarkers and effector molecules in severe sepsis.

PMID- 21849845
TI  - There is no reversible brain death.

PMID- 21849846
TI  - There is no reversible brain death.

PMID- 21849848
TI  - Candida bloodstream infections in intensive care units: an epiphenomenon of
      globalization?

PMID- 21849850
TI  - Translating cancer complexity to clinical decisions.

PMID- 21849849
TI  - Transparency in end-of-life care in the intensive care unit.

PMID- 21849852
TI  - Surgery after induction chemotherapy or chemoradiotherapy for locally advanced
      lung cancer: a technical challenge.

PMID- 21849853
TI  - Fibrous stroma is associated with poorer prognosis in lung squamous cell
      carcinoma patients.
AB  - INTRODUCTION: Cancer tissue is composed of various stromal cells forming cancer
      specific microenvironments. Peritumoral stroma is reportedly composed of
      activated fibroblasts that can influence the biological properties of tumor
      cells, mainly their local aggressiveness and their ability. The aim of this study
      was to examine whether the histological properties of peritumoral stroma are
      correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical
      outcome. METHODS: A series of 220 pathological stage I lung SqCC were categorized
      into two types according to the histological properties of the peritumoral
      stroma, "fibrous stroma type" (n = 85), and "thin stroma type" (n = 135), and
      compared the prognostic significance. Furthermore, we compared the
      immunohistochemical properties of the SqCC cells surrounded by "fibrous stroma"
      with those of the SqCC cells surrounded by "thin stroma." RESULTS: The prognosis
      of the patients with fibrous stroma-type tumors was significantly poorer than
      that of the thin stroma type with regard to both recurrence-free survival (p =
      0.005) and overall survival (p = 0.008). A multivariate analysis showed that the
      presence of a fibrous stroma was an independent prognostic factor (p = 0.030).
      Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous
      stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001)
      and an increased expression of laminin-5gamma2 (94.6 versus 25.0, p = 0.001),
      matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus
      36.5, p = 0.033). CONCLUSION: SqCC with a fibrous stroma displayed higher
      invasive phenotype and were associated with a significantly poor prognosis. The
      current results suggest that the microenvironment created by both SqCC cells and
      the peritumoral fibroblasts may facilitate cancer aggressiveness.

PMID- 21849854
TI  - OPG/RANKL/RANK pathway as a therapeutic target in cancer.
AB  - Bone metastases play an important role in the morbidity and mortality of patients
      with malignant disease. Despite therapeutic advances in the treatment of solid
      organ malignancy such as lung cancer, less development on metastasis
      interventions has been forthcoming. More recent research has focused on molecular
      pathway manipulation in the prevention and treatment of metastatic bone disease
      and associated complications such as bone pain and hypercalcemia. The
      osteoprotegerin/receptor activator of nuclear factor-kbeta ligand/receptor
      activator of nuclear factor-kbeta pathway, which is physiologically involved in
      bone turnover, has been of considerable interest, and recent promising data have
      been revealed. In this study, we describe this molecular pathway in terms of its
      natural physiological function, manipulation for therapeutic benefit, and recent
      clinical trial results.

PMID- 21849855
TI  - miR-101 DNA copy loss is a prominent subtype specific event in lung cancer.
AB  - INTRODUCTION: MicroRNA-101 (miR-101) is frequently downregulated in cancer and
      exhibits antitumorigenic properties, suggesting that miR-101 is a putative tumor
      suppressor. miR-101 is encoded at two loci in the human genome: 1p31.3 (miR-101
      1) and 9p24.1 (miR-101-2). We sought to investigate miR-101 locus-specific
      deletions and genomic loss in the major subtypes of lung cancer. METHODS:
      Analyses of high-resolution array comparative genomic hybridization and single
      nucleotide polymorphism array data were performed to determine the DNA copy
      number status and deletion boundaries of miR-101-1 and miR-101-2 in seven
      independent cohorts that comprised 1,236 lung cancer specimens and 20 lung
      carcinoma in situ samples. miR-101 expression was also investigated in lung
      cancer cell lines and tumors. RESULTS: miR-101 loss at either genomic locus was
      identified in 29% of lung cancers analyzed and was associated with reduced miR
      101 expression. Loss was more frequent at the 9p locus and occurred more often in
      NSCLC as opposed to small cell lung cancer. Lung carcinoma in situ also harbored
      miR-101 deletions, suggesting that genomic loss may be an early event in lung
      cancer development. Finally, miR-101 deletions on 9p were exclusive of CDKN2A
      deletions in several cases, providing evidence that loss of miR-101 is not merely
      a passenger of CDKN2A deletion. CONCLUSIONS: miR-101 genomic loss occurs
      frequently in NSCLC and may be an early event in lung tumorigenesis. DNA
      deletions likely represent a prominent molecular mechanism of miR-101
      downregulation in NSCLC but not in small cell lung cancer.

PMID- 21849856
TI  - Computed tomography perfusion: a new method to evaluate response to therapy in
      lung cancer.

PMID- 21849857
TI  - Novel therapeutic targets in non-small cell lung cancer.
AB  - The development of personalized medicine with a focus on novel targeted therapies
      has supplanted the one-size-fits-all approach to the treatment of many cancers,
      including non-small cell lung cancer. Targeted therapies, if given to a patient
      subpopulation enriched by the presence of relevant molecular targets, can often
      abrogate cell signaling that perpetuates cancer progression. Critical targets
      activating procancer pathways include, but are not limited to, epidermal growth
      factor receptor (EGFR), hepatocyte growth factor receptor (MET), vascular
      endothelial growth factor (VEGF), VEGF receptor, GTPase KRAS (KRAS), receptor
      tyrosine protein kinase erbB-2 (HER2), echinoderm microtubule-associated protein
      like 4-anaplastic lymphoma kinase (EML4-ALK), phosphatidylinositol-4,5
      bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), serine/threonine
      protein kinase B-raf (BRAF), and insulin-like growth factor 1 receptor (IGF-1R).
      Some target-directed therapies, such as epidermal growth factor receptor tyrosine
      kinase inhibitors and anti-VEGF monoclonal antibody, have already been approved
      for clinical use. Others, such as those targeted to MET, VEGFR, HER2, PIK3CA, and
      IGF-1R, are in clinical testing. This review describes molecular targets in non
      small cell lung cancer that are in development or being clinically applied and
      their implications for developing novel anticancer therapies for this previously
      refractory malignancy.

PMID- 21849858
TI  - Tumorlets in familial history of bronchopulmonary carcinoid.

PMID- 21849859
TI  - Tumor cell content for selection of molecular techniques for T790M EGFR mutation
      detection in non-small cell lung cancer.

PMID- 21849861
TI  - Adolescent immunization update.

PMID- 21849862
TI  - Geographic difference in outcomes of congenital toxoplasmosis.

PMID- 21849863
TI  - Pseudomonas mastitis caused by hot tub exposure.

PMID- 21849864
TI  - Can we accurately diagnose tuberculosis infection in children?

PMID- 21849866
TI  - Decreased response after conjugated meningococcal serogroup C vaccination in
      children with Down syndrome.

PMID- 21849867
TI  - Successful treatment with percutaneous transhepatic alcoholization of a liver
      abscess in a child with chronic granulomatous disease.

PMID- 21849868
TI  - The gestalt of case management.

PMID- 21849869
TI  - National Case Management Network of Canada Fifth Annual Conference & Expo:
      promoting excellence and professionalism for case management in Canada.

PMID- 21849870
TI  - Educating ourselves in the changing landscape of case management.

PMID- 21849871
TI  - Recovery Audit Contractor medical necessity readiness: one health system's
      journey.
AB  - PURPOSE: To develop a sustainable approach to Recovery Audit Contractor medical
      necessity readiness that mitigates the regulatory and financial risks of the
      organization. PRIMARY PRACTICE SETTING: Acute care hospitals. CONCLUSIONS:
      Utilizing the model for improvement and plan-do-study-act methodology, this
      health system designed and implemented a medical necessity case management
      program. We focused on 3 areas for improvement: medical necessity review
      accuracy, review timeliness, and physician adviser participation for secondary
      reviews. Over several months, we improved accuracy and timeliness of our medical
      necessity reviews while also generating additional inpatient revenue for the
      health system. We successfully enhanced regulatory compliance and reduced our
      financial risks associated with Recovery Audit Contractor medical necessity
      audits. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: A successful medical necessity
      case management program can not only enhance regulatory compliance and reduce the
      amount of payments recouped by Medicare, but also generate additional inpatient
      revenue for your organization. With health care reform and accountable care
      organizations on the horizon, hospitals must find ways to protect and enhance
      revenue in order to carry out their missions. This is one way for case managers
      to help in that cause, to advocate for the care of their patients, and to bring
      value to the organization.

PMID- 21849873
TI  - Problems and unmet needs of patients discharged "home to self-care".
AB  - PURPOSE OF STUDY: The purpose of this study was to determine the extent to which
      patients discharged "home to self care" experienced problems and unmet needs. A
      secondary aim was to explore potential differences in problems and unmet needs
      between medical and surgical patients. PRIMARY PRACTICE SETTING: The study
      setting was acute care in 2 hospitals that were part of a large academic medical
      center in the Midwest. METHODOLOGY AND SAMPLE: The prospective, cohort survey
      study was designed with a systematic sampling strategy to identify 130
      cognitively intact adults hospitalized for either medical or surgical reasons who
      planned to return home after discharge without formal community services. The
      hospital information system was checked daily to verify whether dispositions were
      coded "home to self care," and to verify whether the patients were not seen by a
      discharge planner. The Problems After Discharge Questionnaire-English Version
      (PADQ-E) was then either mailed or administered via a phone interview
      approximately 1 week after discharge. RESULTS: Overall, 73.8% wanted more
      information about one or more topics related to their care. Most frequently
      mentioned were "when they would be completely recovered" (38.0%) and "where and
      how they could get nursing care at home if they needed it" (36.9%). A majority
      (91.8%) reported difficulties related to at least 1 physical complaint. Pain was
      most frequently mentioned by surgical patients (88.1%). Getting tired quickly was
      an issue for both surgical (76.2%) and medical patients (62.8%). More than 85%
      received help at home from family or friends. Surgical patients received
      significantly more assistance than medical patients with personal care, household
      activities, and mobility. Approximately 1 in 4 surgical patients reported an
      unmet need within the Physical Complaints subscale on the PADQ-E. IMPLICATIONS
      FOR CASE MANAGEMENT PRACTICE: Potential problems that may occur after discharge
      have little chance of getting addressed if not identified during the discharge
      planning process. Standardized, early screening to accurately identify patients
      at risk for unmet needs after discharge is critical to the development and
      implementation of a quality discharge plan. The lack of time available to
      hospital clinicians to assemble and interpret extensive and complex information
      calls for improved methods to support identifying patients at risk for poor
      outcomes, engaging discharge planners efficiently and accurately, providing a
      standardized assessment to identify and address continuing care needs, and
      identifying patients who would benefit from post-acute care. Case managers
      advance their practice by advocating for and participating in the development of
      improved methods.

PMID- 21849875
TI  - Case management takes lead role in educating medical residents.

PMID- 21849876
TI  - Patient-centered care: Anna's story.

PMID- 21849877
TI  - So you want to be an expert.

PMID- 21849878
TI  - Editor's commentary.

PMID- 21849879
TI  - The case manager as expert witness.

PMID- 21849880
TI  - Helping case managers become business partners.

PMID- 21849881
TI  - Case managers take "whole person" approach to workers' compensation cases.

PMID- 21849882
TI  - The value of medical recovery guidelines in workers compensation case management.

PMID- 21849883
TI  - Melorheostosis in the hand and forearm.

PMID- 21849884
TI  - Vestibular rehabilitation therapy in a patient with chronic vestibulopathy of
      ramsay hunt syndrome.
AB  - A 60-yr-old man presented with chronic vestibulopathy induced by Ramsay Hunt
      syndrome for 1 yr. Prolonged dizziness and postural imbalance affected his
      quality-of-life. He was treated using a 2-mo protocol of customized vestibular
      rehabilitation therapy consisting of 16 treatment sessions in a rehabilitation
      clinic and daily home exercises. Significant improvements in the subjective
      perception of dizziness and objective balance function were found. The results
      suggest that vestibular rehabilitation therapy may be an effective therapeutic
      method for chronic vestibulopathy of Ramsay Hunt syndrome.

PMID- 21849885
TI  - Rare knee tumor masked by spasticity in patient with spinal cord injury.

PMID- 21849886
TI  - A new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one,
      synergistically enhances radiation sensitivity in human cervical cancer cells.
AB  - Radiation resistance can be overcome by a combination treatment with chemical
      modifiers. Here, we showed that treatment with 5-bromo-3-(3-hydroxyprop-1-ynyl)
      2H-pyran-2-one (BHP), a new 2-pyrone derivative, in combination with ionizing
      radiation enhances the sensitivity of human cervical cancer cells to ionizing
      radiation through overproduction of reactive oxygen species (ROS). The combined
      treatment with BHP and ionizing radiation caused a decrease in clonogenic
      survival and an increase in apoptotic cell death in cervical cancer cells. The
      combined treatment promoted conformational activation of Bax and led to
      mitochondrial apoptotic cell death. The combination treatment also induced a
      marked increase in intracellular ROS level. Inhibition of ROS attenuated the
      radiosensitizing effect of BHP, concurrent with a decrease in Bax activation, a
      decrease in mitochondrial cell death, and an increase in clonogenic survival.
      These results indicate that BHP synergistically enhances sensitivity of human
      cervical cancer cells to ionizing radiation through elevation of intracellular
      ROS and that ROS-dependent Bax activation is critically involved in the increase
      in apoptotic cell death induced by the combined treatment with BHP and ionizing
      radiation.

PMID- 21849887
TI  - Antitumor effects of the benzophenanthridine alkaloid sanguinarine in a rat
      syngeneic model of colorectal cancer.
AB  - To evaluate the in-vivo preclinical antitumor activity of sanguinarine in a rat
      syngeneic model of colorectal cancer. The effects of sanguinarine on DHD/K12/TRb
      colorectal adenocarcinoma cells were first evaluated in vitro by means of 3H
      thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)
      2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, and terminal transferase dUTP nick
      end labeling (TUNEL) microscopy. For the in-vivo studies, DHD/K12/TRb cells (1.5
      * 106 cells/0.3 ml of sterile saline/animal) were injected subcutaneously in
      syngeneic BDIX rats, which were chronically treated with sanguinarine (5
      mg/kg/day per os) or control diluent. Tumor growth, body weight, hematologic, and
      clinical chemistry measurements were monitored in individual animals at defined
      time intervals. After killing, subcutaneous tumors were explanted from
      experimental animals for histopathological examination. In vitro, micromolar
      concentrations of sanguinarine inhibited dose-dependently DHD/K12/TRb cell
      proliferation and metabolism and induced cell death by apoptosis. In vivo, oral
      administration of sanguinarine induced a significant inhibition of tumor growth
      (P<0.01 vs. untreated controls), in the absence of any toxic or side effects.
      Marked apoptosis and reduced peritumoral vascularization were observed in tumors
      from sanguinarine-treated rats as compared with the controls. Additional basic
      studies are needed to fully characterize the mechanism/s underlying the
      inhibitory effects of sanguinarine on angiogenesis and tumor growth as well as
      the pharmacological and safety profile of this drug in experimental tumor models.
      Overall, findings from this study suggest that sanguinarine is a likely candidate
      for further evaluation in cancer therapy.

PMID- 21849888
TI  - Evaluating the implementation of an online clinical log system for family nurse
      practitioner students.
AB  - This pilot study analyzed the adoption of the Nurse Practitioner Student Tracking
      (NPST) system by a public university's family nurse practitioner graduate
      program. Using the diffusion-of-innovations research framework, the ease of
      transition, acceptance, and perceived advantage of the system were studied in a
      unique group of students (n = 9) and faculty members (n = 6). The study results
      pointed to a more rapid progression through the stages of technological adoption
      for students than for faculty members, a more pronounced acceptance of the
      database by students than by faculty, a higher learning curve for faculty than
      for students, and improved efficiency in clinical logging for students. The NPST
      system served to begin addressing identified issues within the program. Half (n =
      3) of the faculty thought that the NPST system assisted them in ensuring student
      competencies were met. The system also helped them analyze how time was spent in
      clinical practice, identify how much time was spent conferring with preceptor in
      clinical practice, helped students improve the quality of their charting
      practices, and eliminated the concern of dishonest duplication of records. In
      addition, 80% of faculty stated the NPST system helped them see how much time was
      spent with each patient in clinical practice.

PMID- 21849890
TI  - Influence of modest changes in whole-body hydration on tear fluid osmolarity:
      important considerations for dry eye disease detection.

PMID- 21849891
TI  - Oral azithromycin for treatment of posterior blepharitis.
AB  - PURPOSE: To evaluate the effects of oral azithromycin in patients with posterior
      blepharitis. METHODS: Twenty-six eyes of 13 patients with posterior blepharitis
      diagnosed by a qualified ophthalmologist were enrolled in this study. Patients
      were instructed to use oral azithromycin 500 mg per day for 3 days in 3 cycles
      with 7-day intervals. Subjective clinical outcomes were graded and scored 1 day
      before and 30 days after the end of the treatment (53 days after initiating the
      treatment) based on severity scores of: (1) eyelid debris; (2) eyelid
      telangiectasia; (3) swelling of the eyelid margin; (4) redness of the eyelid
      margin; and (5) ocular mucus secretion. For the assessment of global efficacy,
      patients were asked by the investigator to rate the subjective symptoms (eyelid
      itching, ocular itching, eyelid hyperemia, ocular hyperemia, ocular mucus
      secretion, photophobia, foreign body sensation, and dry eye sensation) on a scale
      of 0 (no symptoms) to 5 (severe symptoms). Break-up time, Schirmer I test,
      corneal fluorescein staining score, and rose bengal staining score were also
      performed in all patients. RESULTS: All clinical outcomes scoring showed
      statistically significant improvement after oral azithromycin, except for eyelid
      swelling. Average subjective symptom grading improved statistically after
      treatment with oral azithromycin, except for eyelid hyperemia, photophobia, and
      foreign body sensation. Average tear film break-up time values showed
      statistically significant improvement after the treatment with oral azithromycin.
      No statistically significant improvement was observed on average values of
      Schirmer I test, corneal fluorescein staining score, and rose bengal staining
      score. CONCLUSIONS: The combination of multiple clinical parameters shown in this
      study supports the clinical efficacy of pulsed oral azithromycin therapy for the
      management of posterior blepharitis.

PMID- 21849892
TI  - Comparison of stem cell properties in cell populations isolated from human
      central and limbal corneal epithelium.
AB  - PURPOSE: The limbus of the cornea is said to be the niche for limbal stem cells
      (LSCs) and the primary source of corneal epithelial maintenance. Previously, we
      aimed to have shown that central human epithelial cells are capable of corneal
      regeneration after wounding. In this study, we aimed to investigate whether
      central epithelial cells in human corneas have LSC properties. METHODS: Human
      corneal epithelial cells were separated from the central cornea and the limbus.
      Isolated cells were collected for sphere-forming assay, and spheres formed
      subsequently were analyzed using immunohistochemistry. Fluorescence-activated
      cell sorting (FACS) was also used to analyze epithelial cells from central
      cornea, limbal rim, older donors, younger donors, and dissociated spheres. These
      analyses were based on cell size and Hoechst 33342 dye efflux ability, and side
      populations and non-side populations were isolated for colony growth measurement
      and sphere-forming assay. RESULTS: Human central and limbal epithelial cells were
      capable of forming spheres, in a 1:2 ratio, that were positive for p63
      immunolabeling. In FACS, central and limbal epithelial cells showed no
      significant difference in cell size and dye efflux ability. There were almost 10
      times more large cells with good dye efflux ability from younger donors than from
      older donors, and the gated side population showed more than 4 times faster rate
      of colony growth than the non-side population. Dissociated sphere cells, however,
      did not follow a similar pattern to tissue-derived cells using FACS analysis. In
      these, there were more than twice as many large cells than small cells with good
      dye efflux ability. CONCLUSIONS: Both limbal and central epithelial cells are
      capable of forming spheres in cultures that have stem cell properties. Central
      and limbal epithelial cells cannot be differentiated using FACS, but younger
      donor tissues give rise to greater numbers of large cells with high dye efflux.
      Therefore, results indicate that human central corneal epithelium contains cells
      with stem/progenitor properties, and these stem properties decline with age.

PMID- 21849893
TI  - Reperfusion injury: doublethink or misnomer.

PMID- 21849894
TI  - Calcium and vitamin D requirements for optimal bone mass during adolescence.
AB  - PURPOSE OF REVIEW: There remains very strong interest in the calcium and vitamin
      D requirements of adolescents related to bone health. The Institute of Medicine
      (IOM) released new dietary guidelines in late 2010 for these nutrients. These
      guidelines were primarily based on literature published in 2009 and earlier and
      emphasized the role of vitamin D combined with calcium in optimizing bone health.
      A series of research studies published in 2010 and 2011, mostly not included in
      the IOM report, have further addressed these issues. RECENT FINDINGS: These most
      recently published data are generally consistent with the IOM report and earlier
      data in supporting calcium intakes of 1300 mg/day and vitamin D intakes of 600
      IU/day for adolescents. However, there is some suggestion that a slightly higher
      Recommended Dietary Allowance for vitamin D might be considered at some future
      time. SUMMARY: New dietary guidelines and recent research support increased
      vitamin D intakes compared with previous recommendations, but not very high
      doses. Further studies are needed related to high-dose vitamin D intake.

PMID- 21849895
TI  - Origins of metabolic complications in obesity:  ectopic fat accumulation. The
      importance of the qualitative aspect of lipotoxicity.
AB  - PURPOSE OF REVIEW: This study highlights two aspects of the concept of
      lipotoxicity. First, the metabolic consequences following ectopic fat
      accumulation are not only determined by the amount of lipid accumulated, but also
      the quality of lipid species. Second, the existence of allostatic mechanisms
      operating at cellular and tissue levels, which counterbalance the negative
      effects of lipid overload. RECENT FINDINGS: The development of lipidomics has
      allowed the isolation and identification of a wide range of lipid species. Some
      are highly reactive and capable of inducing undesirable toxic effects. Here we
      focus on recent information related to pathways involved in the production of
      these reactive lipid species, their sites of generation and tropism for specific
      organelles and the molecular mechanisms through which they exert toxic effects.
      We describe how cell membranes and the lipid species forming their bilayer
      constitute the main platform from which reactive lipid species are generated. We
      propose that strategies aimed at maintaining membrane lipid homeostasis are
      fundamental to preventing the initiation of metabolically relevant lipotoxicity.
      SUMMARY: It is essential to understand the qualitative component of lipid species
      involved in cellular toxicity and the molecular mechanisms mediating these toxic
      effects to identify new therapeutic targets.

PMID- 21849897
TI  - Abnormal body composition and early biomarkers of metabolic complications.

PMID- 21849898
TI  - Cost-effective evaluation of the vestibular patient.
AB  - PURPOSE OF REVIEW: There is in existence a large array of sophisticated equipment
      to assess patients with complaints of dizziness and imbalance. Many vestibular
      tests are expensive to administer. In an era of evidence-based medicine and
      economic austerity, the appropriate utilization of such tests is of paramount
      importance. This review examines the clinical value together with costs involved
      in performing the various components of the vestibular assessment battery. RECENT
      FINDINGS: Vestibular testing is expensive. To date, publications to support the
      use of specialist tests for the confident diagnosis of specific vestibular
      pathologies are severely lacking. In fact, over the last 12 months, the
      literature illustrates a reduction in the enthusiasm for some tests that were
      popularized over recent decades. SUMMARY: Tests of vestibular function are
      expensive and their ability to diagnose specific vestibular pathologies is
      lacking. However, there are some tests that, when used in specific circumstances,
      may be very helpful in the diagnosis and management of patients with these
      complaints.

PMID- 21849899
TI  - Science and medicine.

PMID- 21849896
TI  - Origins of metabolic complications in obesity:  adipose tissue and free fatty
      acid trafficking.
AB  - PURPOSE OF REVIEW: Obesity is associated with a number of serious medical
      complications that are risk factors for cardiovascular disease (e.g., insulin
      resistance, dyslipidemia, and liver fat accumulation). Alterations in fatty acid
      trafficking, both between tissues and within cells, represent a key feature in
      the pathophysiology of the metabolic complications in obese patients. The ways by
      which fatty acid 're-routing' may affect metabolic function are summarized in
      this article. RECENT FINDINGS: Ectopic fat accumulation (i.e., fat accumulation
      in nonadipose tissues) appears to be a key feature distinguishing metabolically
      healthy from metabolically abnormal patients. This observation has led to the
      belief that an imbalance in fatty acid trafficking away from adipose tissue
      toward nonadipose tissues is a primary cause for the development of metabolic
      alterations in obese patients. More recently, however, it has become apparent
      that fatty acid trafficking within nonadipose tissues cells (i.e., toward storage
      - in the form of triglycerides - and oxidation) may be equally important in
      determining a person's risk for development of metabolic disease. SUMMARY: The
      pathophysiology of the metabolic alterations associated with obesity is probably
      multifactorial within a complex network of coordinated physiological responses.
      Only through the integration of multiple concepts, will it be possible to further
      our understanding in this area and to help prevent the metabolic alterations
      associated with obesity.

PMID- 21849900
TI  - Advances and challenges in inner ear medicine.

PMID- 21849901
TI  - Enteroscopy in children.
AB  - PURPOSE OF REVIEW: Endoscopic investigation of small bowel disorders in children
      has historically been difficult due to the length and tortuosity of the organ
      itself. New technology introduced over the past decade allows minimally invasive,
      detailed endoscopic evaluation of the small bowel mucosa from the duodenum to the
      cecum. While understudied in the pediatric population, literature is emerging
      supporting the use of these techniques and devices in children. RECENT FINDINGS:
      Well tolerated and clinically useful capsule endoscopy has been reported a number
      of times in children, and the indications and potential complications of this
      procedure are discussed. The limitations of capsule endoscopy, namely inability
      to biopsy and treat small bowel lesions, have been addressed to some extent by
      the introduction of balloon enteroscopy, which allows deep intubation of the
      small bowel, and at times viewing of the entire mucosal surface. Balloon
      enteroscopy has been safely reported in children as small as 13.1  kg, and has
      been successfully performed in children with Roux-en-Y anastomoses in the
      evaluation and therapy of biliary strictures. SUMMARY: New enteroscopic
      techniques now allow detailed investigation and therapy of small bowel lesions in
      a minimally invasive fashion in the pediatric population.

PMID- 21849902
TI  - Transposition of the great arteries.
AB  - PURPOSE OF REVIEW: Transposition of the great arteries (TGA) is a complex
      congenital heart defect usually defined within the group of conotruncal defects.
      Some astonishing similarities between the spiral pattern of great arteries and
      the spiral pattern of snail shells and a possible common genetic mechanism of
      normal and abnormal anatomical aspects of the heart and shells are examined.
      RECENT FINDINGS: The pulmonary vascular resistances in TGA and ventricular septal
      defect (VSD) need to be assessed before surgery, as they are the key factors for
      the success of the surgical procedure. A noninvasive method has been proposed to
      assess this key factor. A first series of the pregnancy outcomes in young women
      after arterial switch operation (ASO) is promising and encouraging for even
      better results. The systemic failing right ventricle (RV) is treated empirically
      using the same drugs and devices as for the failing left ventricle. The rationale
      for the treatment of ventricular failure, similar or different for predominantly
      right or left ventricle, is debated. The results of Rastelli operation are
      compared with those of the other surgical procedures for the treatment of TGA,
      VSD and pulmonary stenosis, namely reparation a l'etage ventriculaire and
      Nikaidoh interventions. SUMMARY: This review outlines some new aspects of the
      embryologic cardiac development and reveals astonishing similarities between
      heart and shells. A new diagnostic noninvasive method for measuring pulmonary
      vascular resistances, the pregnancy outcome of a first series of women operated
      by ASO, and the pharmacological and cardiac devices used in the failing systemic
      RV are presented. Finally, the review comments on the Rastelli operation as the
      'gold standard' for TGA, VSD, and pulmonary stenosis.

PMID- 21849903
TI  - Repeated screening for colorectal cancer with fecal occult blood test in
      Catalonia, Spain.
AB  - The objective of this study was to explore the variables associated with repeated
      screening for colorectal cancer (CRC) among individuals aged 50-69 years in
      Catalonia, Spain. We selected for the study all individuals (n=11 969) screened
      by a population-based CRC screening program in 2004 and who were eligible for
      rescreening in two years. A multilevel logistic regression model was derived. The
      contextual variables were the percentage of people with less than primary studies
      and the percentage of CRC screening participation. The individual variables used
      were: sex, age, CRC screening (prior to 2004), guaiac fecal occult blood test
      result, ease of recruitment, and number of tests used. The rescreening rate was
      87%. No differences according to sex and age were found. The strongest barrier
      for CRC rescreening was an inconclusive fecal occult blood test result at
      baseline screening [odds ratio (OR): 0.24; 95% confidence intervals (CI): 0.20
      0.29]. Individuals who agreed to participate just after receiving the screening
      invitation were more likely to accept a second screen compared with those who
      received a reminder letter six weeks later (OR: 1.53; 95% CI: 1.36-1.73). Those
      individuals who lived in a neighborhood with a higher educational level were more
      willing to rescreen (OR: 1.22; 95% CI: 1.03-1.45) than those who lived in more
      deprived areas. Rescreening was highly adequate in our program, reflecting
      satisfaction with the service received at screening. Strategies to enhance
      initial screening participation for CRC and to improve quality throughout the
      screening process should be prioritized.

PMID- 21849904
TI  - Intestinal tuberculosis: a diagnostic challenge--case report and review of the
      literature.
AB  - Even though tuberculosis is considered rare in developed countries, its rising
      incidence, especially in high-risk populations, places intestinal tuberculosis in
      the differential diagnosis of patients with atypical abdominal symptoms or signs.
      We, herein, report the case of an immunocompetent woman, from a nonendemic area,
      who developed intestinal tuberculosis, emphasizing the diagnostic challenges
      caused due to nonspecific symptoms, inconclusive clinical, laboratory, and
      imaging findings, which could not rule in or rule out tuberculosis.
      Antituberculosis treatment was administered based on endoscopic findings and
      histological features of mucosal biopsies, which were indicative of intestinal
      tuberculosis, and the patient showed a marked clinical and laboratory
      improvement. We also review the evidence with regard to the diagnostic accuracy
      of the different available tests for intestinal tuberculosis.

PMID- 21849905
TI  - Predictors of clozapine discontinuation in patients with schizophrenia.
AB  - Clozapine has superior efficacy for treating patients with schizophrenia. Its
      discontinuation could have detrimental consequences. We attempted to identify the
      clinical parameters that could predict clozapine discontinuation in patients
      diagnosed as having schizophrenia by conducting a retrospective analysis of all
      of those who started on clozapine treatment during their hospitalization in our
      institution between 2002 and 2008 (n=100). Demographic and clinical parameters
      were analyzed and compared between the 58 patients who continued and the 42 who
      discontinued clozapine treatment during a follow-up period of 8.1 years. Twenty
      of the latter patients (47.6%) discontinued clozapine because of nonadherence and
      11 (26.2%) because of side effects. Thirty-three of them (78.6%) stopped taking
      clozapine during the first year of treatment. The duration of clozapine use
      correlated significantly with the time to readmission (P<0.001). The decrease in
      number of suicide attempts was higher in those who continued clozapine treatment
      compared with those who discontinued it (P=0.02). Predictors for drug
      discontinuation were old age at clozapine initiation and comorbid substance
      abuse. These findings indicate that patients with schizophrenia with those risk
      factors need special incentives to be compliant during the first year of
      clozapine treatment to minimize the negative sequelae of clozapine
      discontinuation.

PMID- 21849906
TI  - Do serum angiopoietin-1, angiopoietin-2, and their receptor Tie-2 and 4G/5G
      variant of PAI-1 gene have a role in the pathogenesis of preeclampsia?
AB  - OBJECTIVE: To evaluate whether serum angiogenesis markers such as angiopoietins
      (Ang-1, Ang-2) and their receptor (Tie-2) are altered in women with preeclampsia.
      We also performed genotyping to determine if the 4G/5G genotypes of -675 PAI-1
      gene may play a role in the pathogenesis of preeclampsia. MATERIALS AND METHODS:
      Sixty-eight pregnant women with preeclampsia were compared to 35 normotensive
      pregnant women and 24 normotensive nonpregnant women in a cross-sectional study.
      Using enzyme-linked immunosorbent assay, levels of serum Ang-1 and Ang-2, and Tie
      2 were measured. A single base pair insertion/deletion 4G/5G polymorphism of the
      PAI-1 gene was determined by polymerase chain reaction. RESULTS: Serum levels of
      Ang-1 and Tie-2 were significantly different among the study groups (P = 0.001
      and P = 0.025, respectively) being lower in the preeclamptic group. Positive
      significant correlation was found between Ang-2 and Tie-2, (r = 0.26, P = 0.024).
      The frequency of the genotypes (4G/5G, 4G/4G, and 5G/5G) differed among the
      groups (P = 0.001). Also, the mean of systolic and diastolic blood pressures
      differed significantly according to the PAI-1 genotype being higher in those
      bearing the 4G allele; P = 0.04 and P = 0.023, respectively. CONCLUSION: Sera Ang
      1 and Ang-2, and Tie-2 as well as variants of 4G/5G of PAI-1 polymorphism have
      positive implications in the pathogenesis of preeclampsia.

PMID- 21849907
TI  - Suppressive effects of imidapril on Th1- and Th2-related chemokines in monocytes.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are used to control
      hypertension and are superior to other antihypertensive agents in protecting the
      progressive deterioration of autoimmune-related nephritis. An imbalance of T
      helper 1 (Th1)/Th2 is thought to contribute to the pathogenesis of autoimmune
      diseases and their related glomerulonephritis. I-309 is a Th2-related chemokine
      involved in the recruitment of Th2 cells toward Th2-related inflammation. Tumor
      necrosis factor alpha (TNF-alpha) and Th1-related chemokines, interferon
      inducible protein 10 (IP-10)/CXCL10 are also involved in autoimmune
      glomerulonephritis. However, the modulatory effects and the mechanisms of ACEIs
      on TNF-alpha and Th1- and Th2-related chemokines in monocytes remain poorly
      defined. OBJECTIVE: We investigated the effects of imidapril and perindopril, 2
      ACEIs, on the expression of IP-10, I-309, and TNF-alpha in human monocytes and
      also the associated intracellular mechanism. RESULTS: Imidapril and perindopril
      significantly downregulated lipopolysaccharide (LPS)-induced TNF-alpha, I-309,
      and IP-10 in THP-1 cells and human primary monocytes. All 3 mitogen-activated
      protein kinase inhibitors suppressed LPS-induced TNF-alpha and I-309 expression
      in human primary monocytes. Only extracellular signal-regulated kinases and c-Jun
      N-terminal kinases (JNK) mitogen-activated protein kinase inhibitors suppressed
      LPS-induced IP-10 expression. Lipopolysaccharide-induced mitogen-activated
      protein kinase kinase 4 (MKK4), p-JNK, and c-Jun expression in human primary
      monocytes was suppressed by imidapril. CONCLUSIONS: These data demonstrate that
      ACEI is effective in downregulating LPS-induced TNF-alpha, I-309, and IP-10,
      which play important roles in the pathogenesis of inflammation. Its suppressive
      effect on TNF-alpha, I-309, and IP-10 may, at least in part, involve the down
      regulation of LPS-induced MKK4-JNK-c-Jun expression.

PMID- 21849908
TI  - Nurses' perceptions of simulation-based interprofessional training program for
      rapid response and code blue events.
AB  - Following completion of an interprofessional simulation program for rapid
      response and code blue events, we explored hospital unit nurses' perspectives of
      the training, through a mixed-methods analysis. The results of this study
      advocate for the use of simulation training in preparing nurses and promoting
      communication among team members, effective teamwork, and early recognition of
      clinically deteriorating patients. This study provides support for the
      implementation and continued use of simulation interprofessional programs in
      hospital settings.

PMID- 21849909
TI  - Hospitalized children's perspectives on the quality and equity of their nursing
      care.
AB  - Hospitalized children and adolescents (n = 496), aged 6 to 21 years, were asked
      to evaluate the quality of their nursing care by describing nurse behaviors that
      they liked and disliked. They named 1673 positive nurse behaviors (12 categories)
      that made them feel good, happy, safe, and cared about, including "gives me what
      I need when I need it" (42.3%) and "checks on me often" (34.7%). Six categories
      of negative nurse behaviors (n = 485), such as "does things to me that hurt or
      are uncomfortable" (64.1%) and "wakes me up" (24%), made them feel sad, bad, mad,
      scared, or annoyed.

PMID- 21849910
TI  - Posterior tibial tendon tear after 4-cortex syndesmotic screw fixation:  a case
      report and literature review.
AB  - We describe a previously unreported problem of a patient who underwent errant 4
      cortex syndesmotic screw fixation with resultant posterior tibial tendon tear
      necessitating removal of hardware and repair of a tendon tear.

PMID- 21849911
TI  - A systematic review: plyometric training programs for young children.
AB  - The purpose of this systematic review was to evaluate the efficacy and safety of
      plyometric training for improving motor performance in young children; to
      determine if this type of training could be used to improve the strength, running
      speed, agility, and jumping ability of children with low motor competence; and to
      examine the extent and quality of the current research literature. Primary
      research articles were selected if they (a) described the outcomes of a
      plyometric exercise intervention; (b) included measures of strength, balance,
      running speed, jumping ability, or agility; (c) included prepubertal children 5
      14 years of age; and (d) used a randomized control trial or quasiexperimental
      design. Seven articles met the inclusion criteria for the final review. The 7
      studies were judged to be of low quality (values of 4-6). Plyometric training had
      a large effect on improving the ability to run and jump. Preliminary evidence
      suggests plyometric training also had a large effect on increasing kicking
      distance, balance, and agility. The current evidence suggests that a twice a week
      program for 8-10 weeks beginning at 50-60 jumps a session and increasing exercise
      load weekly results in the largest changes in running and jumping performance. An
      alternative program for children who do not have the capability or tolerance for
      a twice a week program would be a low-intensity program for a longer duration.
      The research suggests that plyometric training is safe for children when parents
      provide consent, children agree to participate, and safety guidelines are built
      into the intervention.

PMID- 21849912
TI  - Physiological and performance changes from the addition of a sprint interval
      program to wrestling training.
AB  - Increasing the level of physical fitness for competition is the primary goal of
      any conditioning program for wrestlers. Wrestlers often need to peak for
      competitions several times over an annual training cycle. Additionally, the
      scheduling of these competitions does not always match an ideal periodization
      plan and may require a modified training program to achieve a high level of
      competitive fitness in a short-time frame. The purpose of this study was to
      examine the effects of 4 weeks of sprint-interval training (SIT) program, on
      selected aerobic and anaerobic performance indices, and hormonal and
      hematological adaptations, when added to the traditional Iranian training of
      wrestlers in their preseason phase. Fifteen trained wrestlers were assigned to
      either an experimental (EXP) or a control (CON) group. Both groups followed a
      traditional preparation phase consisting of learning and drilling technique, live
      wrestling and weight training for 4 weeks. In addition, the EXP group performed a
      running-based SIT protocol. The SIT consisted of 6 35-m sprints at maximum effort
      with a 10-second recovery between each sprint. The SIT protocol was performed in
      2 sessions per week, for the 4 weeks of the study. Before and after the 4-week
      training program, pre and posttesting was performed on each subject on the
      following: a graded exercise test (GXT) to determine VO(2)max, the velocity
      associated with V(2)max (nuVO(2)max), maximal ventilation, and peak oxygen pulse;
      a time to exhaustion test (T(max)) at their nuVO(2)max; and 4 successive Wingate
      tests with a 4-minute recovery between each trial for the determination of peak
      and mean power output (PPO, MPO). Resting blood samples were also collected at
      the beginning of each pre and posttesting period, before and after the 4-week
      training program. The EXP group showed significant improvements in VO(2)max
      (+5.4%), peak oxygen pulse (+7.7%) and T(max) (+32.2%) compared with pretesting.
      The EXP group produced significant increases in PPO and MPO during the Wingate
      testing compared with pretesting (p < 0.05). After the 4-week training program,
      total testosterone and the total testosterone/cortisol ratio increased
      significantly in the EXP group, whereas cortisol tended to decrease (p = 0.06).
      The current findings indicate that the addition of an SIT program with short
      recovery can improve both aerobic and anaerobic performances in trained wrestlers
      during the preseason phase. The hormonal changes seen suggest training-induced
      anabolic adaptations.

PMID- 21849913
TI  - The role of positron emission tomography with computed tomography in the follow
      up of asymptomatic cutaneous malignant melanoma patients with a high risk of
      disease recurrence.
AB  - The aim of this study was to evaluate the role of [F] fluorodeoxyglucose positron
      emission tomography/computed tomography (PET/CT) as a surveillance tool in
      asymptomatic patients with primary cutaneous melanoma with the American Joint
      Committee on Cancer stage 3 disease. Thirty-four patients with primary cutaneous
      malignant melanoma with American Joint Committee on Cancer stage 3 disease, who
      underwent at least one annual surveillance PET/CT scan, were retrospectively
      identified from our PET Centre Database in May 2008 and their characteristics,
      PET/CT results and disease course were reviewed. In 20 patients with microscopic
      stage 3 disease at diagnosis, annual surveillance PET/CT detected two of three
      recurrences and detected one incidental breast carcinoma. In 14 patients with
      macroscopic stage 3 disease at, or subsequent to, their initial diagnosis, annual
      PET/CT detected four of four recurrences, detected metastases in one patient who
      remains asymptomatic and detected one incidental thyroid carcinoma. PET/CT seems
      to be a useful surveillance tool in patients with macroscopic stage 3 disease,
      although the numbers in this study are small. However, the role of PET/CT in
      patients initially presenting with microscopic stage 3 disease requires further
      confirmation.

PMID- 21849914
TI  - Coenzyme Q10 protects neurons against neurotoxicity in hippocampal slice culture.
AB  - This study investigated the neuroprotective effects of coenzyme Q10 (CoQ10)
      against oxidative stress induced by kainic acid (KA) in organotypic hippocampal
      slice culture of rats. Cultured slices were injured by exposure to 5 uM of KA for
      18 h and then treated with different concentrations of CoQ10. Neuronal cell death
      measured as propidium iodide uptake was reduced at 24 h after treatment with 1 uM
      of CoQ10. We also observed an increased number of surviving CA3 neurons in 0.1
      and 1 uM concentrations of CoQ10-treated groups using cresyl violet staining.
      CoQ10 (0.01, 0.1, and 1 uM) treatment significantly decreased the 2',7'
      dichlorofluorescein fluorescence and the expression of NQO1 in the CoQ10-treated
      groups was significantly lower than that in the KA-only group. These results
      suggest that CoQ10 may protect hippocampal neurons against oxidative stress.

PMID- 21849915
TI  - Automaticity in attractive face processing: brain potentials from a dual task.
AB  - Attractive faces have a special status, possibly because of evolutionary reasons.
      We assessed the automaticity of facial attractiveness processing in a dual-task
      paradigm manipulating the availability of cognitive resources to face processing
      by a primary tone task presented at varying stimulus onset asynchrony (SOA). In
      event-related brain potentials, attractive relative to neutral faces induced an
      increased posterior negativity from 260 ms onwards indicating enhanced stimulus
      encoding at the cortical level. Interestingly, effects of attractive faces on
      event-related brain potentials were most pronounced at high temporal overlap with
      the primary task (short stimulus onset asynchrony). This indicates that a
      shortage of cognitive resources may enhance the processing of attractive faces,
      revealing hard-wired processing biases of the human information processing system
      for evolutionarily prepared stimuli.

PMID- 21849916
TI  - Neuronal differentiation potential of mouse induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells have been generated from somatic cells by
      ectopic expression of defined transcription factors. The important issues for
      clinical applications of iPS cells are the defined methods for somatic cell
      differentiation and how to effectively enrich desired cell population. Here we
      used humanized renilla green fluorescent protein under the control of Talpha1
      alpha-tubulin promoter as lineage selection marker for neuronal differentiation
      of iPS cells. Using fluorescence-activated cell sorting, green fluorescent
      protein positive cells were isolated and enriched to near-purity. These results
      indicated that the neuronal differentiation potential of iPS cells derived from
      adult somatic cells is similar to that of embryonic stem cells and the high
      purity neurons may have important implications for neurodevelopmental studies,
      safety pharmacological studies, and transplantation studies.

PMID- 21849917
TI  - Maister Peter Lowe and his 16th century contributions to cranial surgery.
AB  - Before the advent of neurosurgery as a discipline, various historic surgeons
      performed procedures on the skull and brain. One early pioneer of surgery, Peter
      Lowe (c. 1550-1612), not only wrote of methods of cranial surgery in his
      Chirurgerie, which was the first comprehensive text of surgery written in
      English, but also founded what would become the Royal Faculty of Physicians and
      Surgeons. Included in the powers given to him by King James VI was the authority
      to regulate the practices of medicine, surgery, and pharmacy in the west of
      Scotland. This 16th century Scottish surgeon trained in Paris, where he was
      influenced by Ambroise Pare and wrote about the "Spanish sickness." In his
      surgical text, Lowe wrote about his methods of multiple neurosurgical procedures.
      The present study discusses the life of Maister Peter Lowe and reviews his
      contributions to what became the art of neurosurgery.

PMID- 21849918
TI  - Predictive variables for the successful treatment of trigeminal neuralgia with
      gamma knife radiosurgery.
AB  - BACKGROUND: Gamma Knife radiosurgery (GKRS) has been reported to be an effective
      modality to treat trigeminal neuralgia. OBJECTIVE: To determine predictive
      factors for the successful treatment of trigeminal neuralgia with GKRS. METHODS:
      Between 1999 and 2008, 777 GKRS procedures for patients with trigeminal neuralgia
      were performed at our institution. Evaluable follow-up data were obtained for 448
      patients. Median follow-up time was 20.9 months (range, 3-86 months). The mean
      maximum prescribed dose was 88 Gy (range, 80-97 Gy). Dosimetric variables
      recorded included dorsal root entry zone dose, pons maximum dose, dose to the
      petrous dural ridge, and cisternal nerve length. RESULTS: By 3 months after GKRS,
      86% of patients achieved Barrow Neurologic Institute I to III pain scores, with
      43% of patients achieving a Barrow Neurologic Institute I pain score. Twenty-six
      percent of patients reported posttreatment facial numbness; 28% of patients
      reported a post-GKRS procedure for relapsed pain, and median time to next
      procedure was 4.4 years. Multivariate analysis revealed that the development of
      postsurgical numbness (odds ratio [OR], 2.76; P = .006) was the dominant factor
      predictive of efficacy. Longer cisternal nerve length (OR, 0.85; P = .005), prior
      radiofrequency ablation (OR, 0.35; P = .028), and diabetes mellitus (OR, 0.38; P
      = .013) predicted decreased efficacy. The mean dose delivered to the dorsal root
      entry zone dose in patients who developed facial numbness (57.6 Gy) was more than
      the mean dose (47.3 Gy) given to patients who did not develop numbness (P = .02).
      CONCLUSION: The development of post-GKRS facial numbness is a dominant factor
      that predicts for efficacy of GKRS. History of diabetes mellitus or previous
      radiofrequency ablation may portend worsened outcome.

PMID- 21849919
TI  - Neurocognitive impairment in adults with moyamoya disease without stroke.
AB  - BACKGROUND: Adults with moyamoya disease (MMD) have been shown to manifest
      cognitive impairment, but it is unclear whether this is the result of ischemic
      stroke. OBJECTIVE: To determine whether adults with MMD but without stroke have
      cognitive impairment. METHODS: We performed detailed neuropsychological
      assessments in 30 adults with angiographically confirmed MMD without magnetic
      resonance imaging (MRI) evidence of stroke. RESULTS: Twenty patients (67%)
      exhibited small T2 hyperintensities in the cerebral subcortical white matter on
      brain MRI but no evidence of gray matter damage. Significant cognitive
      impairment, defined as half of test scores >= 1 SD below the normal mean, was
      present in 7 patients (23%). Executive functioning, mental efficiency, and word
      finding were the ability areas most frequently impaired, whereas memory was
      relatively intact. Clinically significant emotional distress (depression and/or
      anxiety) was present in 11 patients (37%). Comparable cognitive findings were
      also observed in the subset of 10 patients (33%) with completely normal static
      brain MRI. CONCLUSION: Cognitive impairment in MMD can occur in the absence of
      ischemic stroke as manifested on MRI.

PMID- 21849920
TI  - Accuracy of magnetic resonance imaging-directed frame-based stereotaxis.
AB  - BACKGROUND: Accurate placement of a probe to the deep regions of the brain is an
      important part of neurosurgery. In the modern era, magnetic resonance image (MRI)
      based target planning with frame-based stereotaxis is the most common technique.
      OBJECTIVE: To quantify the inaccuracy in MRI-guided frame-based stereotaxis and
      to assess the relative contributions of frame movements and MRI distortion.
      METHODS: The MRI-directed implantable guide-tube technique was used to place
      carbothane stylettes before implantation of the deep brain stimulation
      electrodes. The coordinates of target, dural entry point, and other brain
      landmarks were compared between preoperative and intraoperative MRIs to determine
      the inaccuracy. RESULTS: The mean 3-dimensional inaccuracy of the stylette at the
      target was 1.8 mm (95% confidence interval [CI], 1.5-2.1. In deep brain
      stimulation surgery, the accuracy in the x and y (axial) planes is important; the
      mean axial inaccuracy was 1.4 mm (95% CI, 1.1-1.8). The maximal mean deviation of
      the head frame compared with brain over 24.1 +/- 1.8 hours was 0.9 mm (95% CI,
      0.5-1.1). The mean 3-dimensional inaccuracy of the dural entry point of the
      stylette was 1.8 mm (95% CI, 1.5-2.1), which is identical to that of the target.
      CONCLUSION: Stylette positions did deviate from the plan, albeit by 1.4 mm in the
      axial plane and 1.8 mm in 3-dimensional space. There was no difference between
      the accuracies at the dura and the target approximately 70 mm deep in the brain,
      suggesting potential feasibility for accurate planning along the whole
      trajectory.

PMID- 21849921
TI  - Angioplasty and stenting for intracranial atherosclerotic stenosis with nitinol
      stent:  factors affecting technical success and patient safety.
AB  - BACKGROUND: Angioplasty and stenting using nitinol stents is a recognized
      treatment option for intracranial atherosclerosis. OBJECTIVE: To identify
      procedure-related factors that may affect patient safety and technical outcome.
      METHODS: In this prospective study of 57 consecutive patients, the primary end
      points were intraprocedural technical problems, periprocedure morbidity, and
      complications. Major periprocedure complication was defined as all stroke or
      death at 30 days. Technical failure was defined as the inability to complete the
      procedure because of technical or safety problems. Procedure failure was defined
      as a procedure outcome of technical failure or major periprocedure complication.
      Secondary end points were procedure-related factors that may affect patient
      safety and technical outcome. RESULTS: Procedure failure rate was 12.3% (7/57)
      (major periprocedure complication rate, 5.3% [3/57]; technical failure rate, 7%
      [4/57]). Initial failure in tracking of balloon or stent occurred in 20 patients,
      other technical problems occurred in 11 patients, including kinking or trapping
      of balloon catheter (2 cases), difficulty in unsheathing of stent (3 cases),
      forward migration of stent during deployment (4 cases), trapping of nose cone
      after stent deployment (1 case), fracture of delivery system (2 cases), and
      guidewire fracture (1 case). Unfavorable vascular morphology signified by the
      presence of 2 or more reverse curves along the access path was found to associate
      with initial failure in the tracking of instruments (OR = infinity), and
      occurrence of other technical problems (OR = 25). CONCLUSION: Procedure-related
      factors could be identified and lead to improvements in patient safety and
      technical outcome. Tortuous vascular morphology is a key factor to be overcome.

PMID- 21849922
TI  - Deep brain stimulation in area LC controllably triggers auditory phantom
      percepts.
AB  - BACKGROUND: Tinnitus is predominantly viewed as the consequence of dysfunctional
      hyperactivity, plastic change, or synchronized oscillations in the central
      auditory system. An alternative to the current auditory-centric view of auditory
      phantom perception is the basal ganglia-centric view. Recent electrical
      stimulation experiments in area LC, a locus of the caudate nucleus positioned at
      its anterior body, has shown loudness modulation of existing tinnitus percepts.
      OBJECTIVE: To demonstrate that auditory phantoms are gated by the dorsal
      striatum. METHODS: Electrical stimulation in area LC via a deep brain stimulation
      lead was performed in 6 interactive adult subjects (3 with and 3 without chronic
      tinnitus) undergoing surgery to treat movement disorders. Tinnitus loudness was
      rated on a 0 to 10 scale, sound quality was described, and localization was
      referenced to 1 or both ears. RESULTS: Short-term area LC stimulation triggered
      new phantom tones, clicks, and frequency modulated sounds in 5 subjects and
      altered sound quality of an existing tinnitus percept in 1 subject. The results
      of this study indicate that perceptual awareness of auditory phantoms is
      contingent on satisfying a permission condition controlled by the dorsal
      striatum. Potential auditory phantoms are not automatically gated to reach
      perceptual awareness. A phantom percept gate control model is proposed.
      CONCLUSION: Neuromodulation of area LC can trigger temporary gate dysfunction and
      reversibly release new phantoms for conscious awareness. Restoration of
      restrictive dorsal striatal gate function to treat problematic phantom percepts
      may be realized by adopting long-term area LC neuromodulation and choosing
      optimal stimulation parameters.

PMID- 21849923
TI  - An introduction to comparative effectiveness research.
AB  - Research examining the process of deciding between treatment alternatives, the
      applicability of the existing literature to this process, and the way that this
      knowledge can be applied to inform clinical decisions is termed comparative
      effectiveness research (CER). Despite its emerging role in both clinical medicine
      and public policy, many neurosurgeons are unaware of the history of CER, the
      principles fundamental to its implementation, and the nature and extent to which
      it impacts patient care. We present a review of literature that provides a brief
      history of the evolution of CER, an overview of its scientific, financial, and
      public policy implications, and a discussion of its implementation and potential
      significance in modern clinical practice. We discuss how CER seeks to combine
      treatment efficacy data with quality of life, outcomes, and other forms of
      effectiveness data to guide selection of optimal patient management strategies.
      This research paradigm strengthens the final step in clinical research that
      should follow the traditional demonstration of efficacy and reemphasizes the
      potentially important role of observational and retrospective investigations in
      establishing effectiveness of efficacious procedures in actual application to
      individual patients. It is useful for neurosurgeons to understand the CER model,
      because it occupies an emerging role in both clinical medicine and public policy
      and presents a potentially useful model for informing medical decision-making in
      the type of real-world situations commonly encountered by clinical neurosurgeons.

PMID- 21849924
TI  - JS-K, a glutathione S-transferase-activated nitric oxide donor with
      antineoplastic activity in malignant gliomas.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) control multidrug resistance and
      are upregulated in many cancers, including malignant gliomas. The
      diazeniumdiolate JS-K generates nitric oxide (NO) on enzymatic activation by
      glutathione and GST, showing promising NO-based anticancer efficacy. OBJECTIVE:
      To evaluate the role of NO-based antitumor therapy with JS-K in U87 gliomas in
      vitro and in vivo. METHODS: U87 glioma cells and primary glioblastoma cell lines
      were exposed to JS-K and a variety of inhibitors to study cell death by necrosis,
      apoptosis, and other mechanisms. GST expression was evaluated by
      immunocytochemistry, polymerase chain reaction, and Western blot, and NO release
      from JS-K was studied with a NO assay. The growth-inhibitory effect of JS-K was
      studied in a U87 xenograft model in vivo. RESULTS: Dose-dependent inhibition of
      cell proliferation was observed in human U87 glioma cells and primary
      glioblastoma cells in vitro. Cell death was partially induced by caspase
      dependent apoptosis, which could be blocked by Z-VAD-FMK and Q-VD-OPH. Inhibition
      of GST by sulfasalazine, cGMP inhibition by ODQ, and MEK1/2 inhibition by UO126
      attenuated the antiproliferative effect of JS-K, suggesting the involvement of
      various intracellular death signaling pathways. Response to JS-K correlated with
      mRNA and protein expression of GST and the amount of NO released by the glioma
      cells. Growth of U87 xenografts was reduced significantly, with
      immunohistochemical evidence for increased necrosis and apoptosis and reduced
      proliferation. CONCLUSION: Our data show for the first time the potent
      antiproliferative effect of JS-K in gliomas in vitro and in vivo. These findings
      warrant further investigation of this novel NO-releasing prodrug in gliomas.

PMID- 21849925
TI  - A novel scoring system for assessing Chiari malformation type I treatment
      outcomes.
AB  - BACKGROUND: Outcome assessment for the management of Chiari malformation type 1
      is difficult because of the lack of a reliable and specific surgical outcome
      assessment scale. Such a scale could reliably correlate postoperative outcomes
      with preoperative symptoms. OBJECTIVE: We developed a novel scoring system and
      applied it retrospectively to 146 patients treated at our institution in order to
      create and verify a simple and quantifiable assessment of Chiari outcomes.
      METHODS: The Chicago Chiari Outcome Scale (CCOS) uses 4 postoperative outcome
      categories (pain, nonpain symptoms, functionality, and complications) graded 1 to
      4 for a total possible score of 16. As a comparison with current Chiari outcome
      methodology, each patient was also placed into a gestalt outcome group of
      "improved," "unchanged," or "worse" (I/U/W). Patients were stratified by CCOS
      scores and by I/U/W group. RESULTS: Stratifying patients by total CCOS scores
      showed that patients who achieved CCOS scores between 13 and 16 were
      predominantly in the I/U/W improved group (n = 101, 69%); scores between 9 and 12
      were predominantly I/U/W unchanged (n = 39, 27%), and scores between 4 and 8 were
      I/U/W worse (n = 6, 4%). Symptom subscore results provided insight into the
      specifics of the overall outcome in addition to the more quantitative nature of
      the 16-point scale. CONCLUSION: We describe a CCOS that assigns higher scores to
      patients judged improved by gestalt I/U/W ratings and lower scores to those who
      were unchanged or worse while defining outcome in 4 specific subcategories. As
      such, this CCOS should allow for a more unified and quantifiable outcome
      assessment after Chiari surgery.

PMID- 21849926
TI  - Gastroesophageal reflux studies using milk in infants and children--the need for
      multiple views.
AB  - The aim of this study was to assess the value of multiple acquisitions in
      detecting position-related gastroesophageal reflux (GER). We retrospectively
      reviewed milk scans of 105 patients with suspected GER and possible lung
      complications. After 2 h of fasting, 11.4 MBq Tc-99m-sulfur colloid was given to
      the patient orally along with formula or milk (infants). Without sedation in most
      patients, serial images (30 s each for 15 frames=8 min) were acquired in the
      supine, prone, right-side down, and left-side down positions. If reflux was
      detected in one position, before proceeding to the next position the patient was
      given water or milk to clear the esophagus.The study was considered positive if
      the activity reappeared in the esophagus. Anterior and posterior chest images
      were obtained after a delay of 2-4 h to detect any pulmonary aspiration. A total
      of 59 patients (56.2%) tested negatively for GER in all four positions and also
      showed a negative delayed scan for pulmonary aspiration. In contrast, 46 patients
      tested positively for GER in variable positions (prone=4, supine=6, left-side
      down=3, right-side down=12, and in more than one position=21, of which six
      included the supine position). The percentage yield of a positive GER position
      related technique was three-fold that of conventional single supine position.
      These results may aid a better understanding of the pathophysiology of the
      disease and the design of preventive and therapeutic measures.

PMID- 21849927
TI  - Effects of different doses of radioactive iodine for remnant ablation on
      successful ablation and on long-term recurrences in patients with differentiated
      thyroid carcinoma.
AB  - OBJECTIVES: The aim of this study was to compare ablation success and disease
      free survival (DFS) on the basis of different ablation doses. METHODS: This
      retrospective study enrolled differentiated thyroid carcinoma patients who
      underwent total thyroidectomy and radioactive remnant ablation at the Asan
      Medical Center between January 2000 and December 2004. Radioactive iodine doses
      of 30 mCi (group A), 80 mCi (group B), and 150 mCi (group C) were administered
      according to the patients' risk of recurrences based on the clinicopathologic
      parameters at the time of surgery. Ablation success was defined as absence of
      abnormal uptake on diagnostic whole-body scan. RESULTS: Among 1024 patients,
      successful ablation was achieved in 81.7% in group A, in 89.5% in group B, and in
      94.8% in group C (P<0.001). A total of 100 patients (9.8%) had clinical
      recurrences during 6.6 years of median follow-up. DFS was evaluated according to
      ablation success in each dose group. There were no significant differences in
      DFS. Side effects of radioactive iodine were negligible with dose up to 80 mCi;
      however, 2% of patients developed permanent salivary dysfunction in group C.
      CONCLUSION: In cases of different ablation doses administered according to
      patients' risk of recurrences, we found that a higher dose of radioiodine was
      associated with a higher rate of ablation success compared with lower doses.
      However, successful ablation was not associated with a reduction in clinical
      recurrences. The optimal dose for ablation must be adjusted according to the risk
      group of individual patients to avoid unnecessary radiation and maximize
      therapeutic efficacy.

PMID- 21849928
TI  - Impact of UDP-gluconoryltransferase 2B17 genotype on vorinostat metabolism and
      clinical outcomes in Asian women with breast cancer.
AB  - OBJECTIVES: Vorinostat, a histone deacetylase inhibitor being actively evaluated
      in solid tumors, is metabolized by UGT2B17. UGT2B17 null genotype (UGT2B17*2) has
      been shown in vitro to reduce UGT2B17 activity. This variant is common in Asians
      but rare in Caucasians, and we studied its impact on vorinostat pharmacokinetics
      and pharmacodynamics in a clinical study in Asian patients with metastatic breast
      cancer. METHODS: Eligible patients received 400 mg of vorinostat monotherapy
      daily in a lead-in phase I followed by a phase II study. Patients were genotyped
      for UGT2B17*2, which was correlated with vorinostat pharmacokinetics and clinical
      outcomes. RESULTS: Twenty-six patients were treated with no complete response,
      one partial response, six stable disease lasting for 12 weeks or more, and 19
      progressive disease. Sixteen patients (62%) were UGT2B17*2 homozygotes and had
      significantly lower mean area under the curve ratio of vorinostat-O
      glucuronide/vorinostat (1.84 vs. 2.51 on day 1, P=0.02; 1.63 vs. 2.38 on day 15,
      P=0.028), and trended toward having higher vorinostat area under the curve
      (399.02 vs. 318.40, P=0.188), more serious adverse events (31 vs. 0%, P=0.121),
      higher clinical benefit rate (40 vs. 10%, P=0.179), and longer median progression
      free survival (3.0 vs. 1.5 months, P=0.087) than patients with at least one wild
      type allele. CONCLUSION: UGT2B17*2 genotype reduces vorinostat glucuronidation
      and may increase vorinostat efficacy and toxicity. These observations are
      important in the development of vorinostat, and may have clinical implications on
      other cancer and noncancer drugs that are UGT2B17 substrates such as exemestane
      and ibuprofen.

PMID- 21849930
TI  - Pretransplant low CD3+CD25high cell counts or a low CD3+CD25high/CD3+HLA-DR+
      ratio are associated with an increased risk to acute renal allograft rejection.
AB  - BACKGROUND: Detection of markers predicting allograft rejection is important for
      risk assessment before kidney transplantation, as well as to minimize
      posttransplantation immunosuppression. METHODS: We studied the expression of
      CD25, HLA-DR, CD134, CD62L, and CD44 by flow cytometry in CD4, CD8, and CD3
      cells, from pretransplant blood samples from 91 transplanted patients accounting
      for 16 episodes of acute renal rejection in the first month after
      transplantation. RESULTS: None of the activation markers showed a significant
      association to acute rejection. Early rejectors showed less pretransplant CD3CD25
      cells than nonrejectors (0.79%+/-0.50% vs. 1.51%+/-0.79% of CD3 cells; P=0.001)
      and a lower CD3CD25/CD3HLA-DR ratio (0.043+/-0.034 vs. 0.111+/-0.079; P<0.00001).
      When levels of CD25 cells fell below 0.7% of CD3 cells, the odds ratio of
      suffering an episode of acute rejection was 105 fold (95% confidence interval:
      11.41-966.43, P<0.0001), with a sensitivity (true-positive results) of 0.63 and a
      specificity (true-negative results) of 0.98 for predicting the risk of acute
      rejection. Furthermore, when the CD3CD25/CD3HLA-DR ratio fell below 0.04, the
      odds ratio of suffering an episode of acute rejection was 7.71 fold (95%
      confidence interval: 2.29-25.97, P=0.001), with a sensitivity of 0.56 and a
      specificity of 0.86 for predicting risk of acute rejection. CONCLUSIONS: Our
      results suggest that low pretransplant levels of CD3CD25 cells or a low
      CD3CD25/CD3HLA-DR ratio could identify those patients with an increased risk of
      early acute allograft rejection. If these data can be independently confirmed,
      pretransplant CD3CD25 cells and the CD3CD25/CD3HLA-DR ratio might provide
      additional information for risk assessment before kidney transplantation.

PMID- 21849931
TI  - Management of primary symptomatic lymphocele after kidney transplantation: a
      systematic review.
AB  - BACKGROUND: Management of lymphoceles after kidney transplantation is highly
      variable. The aim of this study was to evaluate and compare the different
      approaches of lymphocele management among kidney transplant recipients. METHODS:
      MEDLINE and EMBASE were systematically searched for case studies published
      between 1954 and 2010. Inclusion criteria were symptomatic lymphoceles developing
      in recipients of deceased or living donor kidneys with specified intervention and
      outcome. Primary outcome was the rate of recurrence. Secondary outcomes were the
      rate of conversion from laparoscopic to open surgery, hospital stay, and
      complication rates. RESULTS: Fifty-two retrospective case series with 1113 cases
      of primary lymphocele were selected for review. No randomized controlled trials
      or prospective cohort studies were located. Primary treatment modalities included
      were as follows: aspiration (n=218), sclerotherapy (n=155), drainage (n=219),
      laparoscopic surgery (n=333), and open surgery (n=188). Of the 218 cases of
      lymphocele managed with aspiration alone, 141 recurred with a recurrence rate of
      59% (95% confidence interval [CI]: 52-67). Among those who received laparoscopic
      and open surgery, the recurrence rates were 8% (95% CI: 6-12) and 16% (95% CI: 10
      24), respectively. The conversion rate from laparoscopic to open surgery was 12%
      (95% CI: 8-16). CONCLUSIONS: Laparoscopic fenestration of a symptomatic
      lymphocele is associated with the lowest risk of lymphocele recurrence. However,
      the evidence base to support a recommendation for laparoscopic surgery as first
      line treatment is weak and highlights the need for a multicenter prospective
      cohort study to examine the benefits of incorporating initial simple aspiration
      into the management of lymphocele after kidney transplantation.

PMID- 21849933
TI  - Simple and rapid method for the determination of uric acid-independent
      antioxidant capacity.
AB  - Determination of the relative contribution of uric acid level increases to the
      total measured antioxidative activity could be very useful for testing
      antioxidative products and their effect on human health. The aim of this report
      is to present a simple spectrophotometric method that combines the measurement of
      total antioxidative capacity of a sample by ferric reducing/antioxidative power
      (FRAP) assay, with the uricase-reaction (specific elimination of uric acid), in
      order to establish and correct for the contribution of uric acid in FRAP values.
      We measured FRAP values, with (uric acid-independent antioxidant capacity, TAC
      UA) and without (total antioxidant capacity, TAC) uricase treatment, and
      expressed it as MUmol/L of uric acid equivalents. In such way, it was possible to
      determine both total and uric acid-independent antioxidant capacity, plasma uric
      acid (UA, as the difference between TAC and TAC-UA), and the ratio of the uric
      acid in total antioxidant capacity (UA/TAC).

PMID- 21849932
TI  - Development of a highly sensitive and specific immunoassay for determining
      chrysoidine, a banned dye, in soybean milk film.
AB  - A highly specific and sensitive indirect competitive enzyme-linked immunosorbent
      assay (icELISA)was developed for the first time for the detection of chrysoidine,
      a dye banned in soybean milk film. Two haptens with different spacer arms were
      synthesized to produce antibodies. Both homologous and heterologous immunoassay
      formats were compared to enhance the icELISA sensitivity. The heterologous
      icELISA exhibited better performance, with an IC(50) (50% inhibitory
      concentration) of 0.33 ng/mL, a limit of detection (LOD, 10% inhibitory
      concentration) of 0.04 ng/mL, and a limit of quantitation (LOQ, 20%-80%
      inhibitory concentration) from 0.09 to 4.9 ng/mL. The developed icELISA was high
      sensitive and specific, and was applied to determine chrysoidine in fortified
      soybean milk film samples. The results were in good agreement with that obtained
      by high-performance liquid chromatography (HPLC) analyses.

PMID- 21849935
TI  - 20-hydroxyeicosatetraenoic acid, endothelial dysfunction and hypertension.
AB  - 20-hydroxyeicosatrienoic acid (20-HETE) is a metabolite of arachidonic acid
      formed by the enzymatic activity of cytochrome P450 omega hydroxylases of the 4A
      and 4F isoform families (CYP 450 4A and 4F). The role of the metabolites of
      arachidonic acid (AA) formed by cyclooxygenases and lipoxygenases in mediating
      cardiovascular function have been studied and known for a long time. More
      recently, particularly in the last 10-15 years, the importance of the role that
      the CYP450 omega hydroxylase/20-HETE system plays in cardiovascular, inflammatory
      and neoplastic diseases, has captured the attention of the scientific community.
      In this brief review we discuss some of the more recent findings related to the
      function of 20-HETE in the cardiovascular system. In particular we focus on the
      interactions of 20-HETE with the intracellular pathways of nitric oxide and the
      renin angiotensin system and discuss how it plays a role in oxidative stress, the
      development of endothelial dysfunction and experimental and human hypertension.
      To date the research strongly suggests that 20-HETE is an important and central
      mediator of cardiovascular function, and that alterations in the normal
      regulation of the CYP450/20-HETE system play a role in the pathogenesis of many
      disorders. There is great potential for the development of therapeutic agents to
      modify the activation and activity of this system in order to prevent and/or
      treat hypertension.

PMID- 21849936
TI  - Three different approaches to Transversus abdominis planeblock: a cadaveric
      study.
AB  - AIM: The transversus abdominis plane (TAP) block is a new technique for providing
      analgesia to the anterior abdominal wall. There is ongoing debate regarding
      access point for TAP block. The aim of this cadaveric study was to compare the
      spread of 40 mL of dye using three different approaches to TAP: subcostal , via
      the mid-axillary and via the lumbar triangle of Petit (LTOP). METHODS: Injection
      of black dye into the TAP was performed for each hemi-abdominal wall of 13
      embalmed human cadavers by using 3 different access points: subcostal (9 hemi
      abdomens), mid-axillary (9) and LTOP (8). This was followed by dissection to
      determine the extent of dye spread and nerve involvement in the dye injection.
      The shapes of the dye were traced onto clear plastic, which was then
      photographed. These digital photographs were loaded into the mathematical
      software programme Matlab, and the outline of the dye spread was digitised using
      a piecewise cubic spline, enabling the shapes to be plotted on a graph and the
      areas to be calculated. RESULTS: The area of the dye spread for subcostal, mid
      axillary and LTOP was 85.1 (T7-L1), 58.9 (T10-L1) and 77.9 cm2 (T10-L1),
      respectively. There was statistically significant difference between area of dye
      spread between subcostal and mid-axillary approach (p<0.01). CONCLUSIONS: This
      dye injection study in a cadaver model indicates that subcostal approach is
      associated with a larger area of spread of dye than the mid-axillary approach.
      Dye injected through subcostal, mid-axillary and LTOP approaches demonstrated
      different nerve involvement.

PMID- 21849937
TI  - Impaired kidney function in rats six months after unilateral nephrectomy - an old
      story, a new perspective.
AB  - AIM: Despite of routinely practised living kidney transplantation, data on
      consequences and impact of unilateral nephrectomy on the quality of life and
      health of donors are scarce. The aim of the present study was to examine long
      term changes and function of the remnant kidney after unilateral nephrectomy in
      an animal model. METHODS: Thirty six female Sprague - Dawley rats at 4 months of
      age were randomized into the three groups: unilaterally nephrectomized, sham
      operated and naive rats. The nephrectomy was done at inclusion in the experiment
      and their blood was taken at inclusion and six months thereafter. RESULTS: There
      was a significant increase in serum creatinine concentrations six months after
      unilateral nephrectomy (39.7 +/- 0.8 MUmol/l) in comparison with the sham
      operated (30.1 +/- 1.1 MUmol/l) and the naive rats (26.3 +/- 3 MUmol/l) (p <=
      0.001). Serum sodium levels remained unchanged (p=0.116). Blood haemoglobin
      concentration did not differ between the three groups (p=0.115). CONCLUSIONS:
      Although it has been very well established that kidney possesses huge capacity to
      compensate severe loss of renal mass, our results implicate that renal function
      undergoes significant deterioration with time after unilateral nephrectomy.
      Fortunately, in everyday clinical practice we do not see severe renal dysfunction
      in patients with a single kidney. However, prolongation of the human life span in
      the future could face us with renal impairment in living kidney donors. Future
      examination of specific biomarkers in our rat model (e.g. growth factors) could
      support our findings.

PMID- 21849938
TI  - Humoral immune system state in beta thalassemia major.
AB  - AIM: To investigate the humeral immune markers in patients with beta-thalassemia
      major (TM). METHODS: In this historical - cohort study (August to December 2007),
      the case group consisted of 34 TM patients and the control group included the
      same number of their gender and age matched healthy siblings. Serum levels of
      CH50, C3, C4, IgE, IgG,IgA,IgM and also ASO and Isohemaglutinin titers were
      determined and compared between the case and control groups (P<0.05). RESULTS:
      Serum level of IgA in TM patients was more frequently higher than normal level
      compared to the controls, but there were no significant differences on the level
      of C3, C4, CH50, IgG, IgE, IgM, ASO and Isohemaglutinin between two groups.
      Splenectomized patients had lower IgM and higher IgA and IgG levels and also
      diabetic patients had significantly lower C3, ASO, IgM and higher IgA and IgG
      levels than other patients. Levels of IgA, IgE, IgG, and ASO increased in elder
      patients. Patients with serum ferritin level >3000 ng/ml had lower C4 and CH50
      levels. C4-level in male patients was significantly lower. CONCLUSIONS: This
      study indicated that there were no significant changes in humeral immune markers
      in the patients with beta-thalassemia major compared to the controls, except in
      the case of IgA which was higher in the TM patients. It seems that there is no
      need for routine survey of immunoglobulins and complement levels in thalassemic
      patients in order to detect immunodeficiency.

PMID- 21849939
TI  - A simplified proximal isovelocity surface area method for mitral valve area
      calculation in mitral stenosis: not requiring angle correction and calculator.
AB  - AIM: To simplify proximal isovelocity surface area (PISA) method for mitral valve
      area (MVA) calculation that does not necessitate the usage of a calculator and
      angle correction, and to compare values estimated using this novel method with
      the values obtained by the conventional PISA, planimetry and pressure half-time
      (PHT) methods. METHODS: We evaluated patients with a wide range of mitral
      stenosis (MS) severity. The MVA was measured by the methods of PHT (MVA PHT),
      planimetry (MVApl), conventional PISA (MVAC-PISA) and the novel method of simple
      PISA (MVAS-PISA). Application of simple PISA was performed subsequently by
      division of the peak mitral inflow velocity by four; measurement of the radius by
      adjusting the aliasing velocity to this value; square of the radius gives the
      MVAS-PISA. RESULTS: Twenty patients were enrolled in the study. Peak and mean
      pressure gradients of patients were 20 +/- 6 mmHg and 10 +/- 4 mmHg,
      respectively. The average values of MVApl, MVAPHT, MVAC-PISA, and MVA S-PISA were
      1,54 +/- 0,41, 1,65 +/- 0,40, 1,58 +/- 0,42, 1,57 +/- 0,44 cm2, respectively.
      MVAS-PISA had a strong correlation with the MVAC-PISA, MVApl and MVAPHT .
      Furthermore, there was no significant difference between simple PISA and the
      other methods. The agreement between planimetry and simple PISA methods for
      detecting severe mitral stenosis (MVA <1.5 cm2) determined by ROC analysis was
      very good with a sensitivity and specificity of 100 % and 92%, respectively.
      CONCLUSIONS: Simple PISA is a user friendly method which does not take time and
      gives simple and correct results. If the diagnostic power of the technique is
      proven by more comprehensive studies, it can supersede the conventional PISA
      method.

PMID- 21849940
TI  - Dietary magnesium intake and coronary heart disease risk: a study from Serbia.
AB  - AIM: To assess the relationship between dietary magnesium intake and the risk of
      coronary heart disease (CHD). METHODS: A conducted case-control study included
      290 randomly selected cases (mean age 59.98 +/- 10.03 years) with first event of
      an acute coronary syndrome and 290 selected controls paired by sex, age and
      region (mean age 59.43 +/- 10.10 years) admitted to the same hospitals without
      any suspicion of coronary disease. A diet was assessed by an interviewer
      administered semi-quantitative food frequency questionnaire, and magnesium intake
      was derived from the nutrient database. RESULTS: Subjects with coronary heart
      disease had significantly lower intake of foods containing high levels of
      magnesium like whole grain (p<0.0001), legumes (p<0.05) and nuts (p<0.05). Lower
      dietary magnesium intake was found to be positively associated with risk of
      coronary heart disease (0.027). CONCLUSIONS: Our findings suggest that dietary
      intake of magnesium was associated with reduced risk of coronary heart disease
      among Serbian population.

PMID- 21849941
TI  - Cognitive dysfunction in idiopathic and vascular parkinsonism.
AB  - AIM: To evaluate the characteristics of cognitive disturbances in patients with
      parkinsonism and to point out the need of following up those changes by highly
      specific tests. METHODS: The first group consisted of patients with Parkinson's
      disease, and the second group of patients with vascular parkinsonism. The
      neuropsychological assessments were performed with mini mental state examination
      (MMSE) and the Raven progressive matrices. RESULTS: The MMSE has shown a higher
      percentage of patients with vascular parkinsonism who had dementia. For
      evaluating the nonverbal possibilities, the aim of understanding the complex
      situation and the visual perception, the Raven's progressive matrices were used
      showing that in both groups of the patients those specific changes were highly
      present. CONCLUSIONS: It was concluded that MMSE and Raven's progressive matrices
      have to be obtained in early phases of the disease, and have to be repeated to
      follow up the therapy effect.

PMID- 21849943
TI  - Psychical and psychological characteristics of patients with nonepileptic
      seizures.
AB  - AIM: To explore psychic and psychological characteristics of patients suffering
      from non- epileptic seizures and compare them with the patients suffering from
      epilepsy. METHODS: Using medical documentation 40 patients with non epileptic
      seizures were compared with 40 randomly selected epilepsy patients according to
      psychiatric and psychological report, and using psychotropic medications.
      RESULTS: Both psychiatric and psychological reports have shown that pathologic
      changes were more frequently found within the epilepsy group (n = 20 and n=7,
      respectively) than in non-epileptic fits group (n= 18 and n=4, respectively). Six
      patients had neurotic disorders within the epilepsy group, versus 3 within the
      non-epileptic fits group. Conversion disorders were more frequently found within
      the non-epileptic group (n=6) as compared to epilepsy group (n=2). Disorders due
      to acute reaction to stress occurred in six patients in the non-epileptic fits
      group versus three patients in the epilepsy group. Cognitive disorders were found
      more frequently within the epilepsy group (n=6) as compared to the non-epileptic
      fits group (n=1). Vulnerable character, adolescence crisis, deficit of social
      abilities and indifference were more frequently found within the non-epileptic
      fits group (n=3) in comparison with the epilepsy group (n=1). CONCLUSIONS:
      Psychiatric and psychological reports are most important elements in the
      diagnostic of psychogenic non-epileptic seizures.

PMID- 21849942
TI  - Risk of the recurrent headache and migraine appearance within the family.
AB  - AIM: The aim of this research was to determine the risk for family appearance of
      the recurrent headache (non-migraine and migraine). METHODS: The research was
      conducted in Vojvodina, the Northern Province of Serbia. The population of
      Vojvodina is around 2 million people belonging to more than 20 different ethnic
      groups. During the 20-year period (1988-2008), 30,363 children aged 3 to 17 years
      were tested, independent of their place of birth. The presence of headaches
      similar to those tested was compared among all the members of the family within
      three generations. RESULTS: Positive family data of the recurrent headaches were
      detected among 98.6% children with migraine headaches, 64.7% children with non
      migraine headaches, and 32.4% children without recurrent headaches. The relation
      among the members of the nuclear family (contingency quotient of 0.429) was
      significantly stronger than the relation to the members of wider family
      (contingency quotient of 0.338). CONCLUSIONS: The probability of a child having
      the migraine headache rather than the non-migraine one was very high for parents
      and high for father's mother, while it was not significant for mother's mother,
      mother's father and father's father, having similar recurrent headaches.

PMID- 21849944
TI  - Biometeorological phases influence on stroke morbidity.
AB  - AIM: To determine influence of biometeorological phases on stroke incidence
      according to age and gender of patients, place of residence, days in a week,
      months in a year, type of stroke, additional diagnosis. METHODS: Comparative
      analysis of the data on stroke patients (according to age, months, days, place of
      residence, age, sex, stroke type, additional diagnosis and number of
      hospitalization days) obtained by examining the records of discharge and
      admission of patients in the Department of Neurology of Kragujevac and everyday
      biometeorological phases obtained from the Republic Hydrometeorological Service
      of Serbia (RHMS of Serbia), for the following years: 2003, 2004, 2007, 2008 and
      2009 in Kragujevac. RESULTS: 4,700 patients diagnosed with stroke were
      hospitalized in the observed period. The highest number of strokes was noted in
      2003 (1,030), the lowest in 2008 (851). The highest number of strokes was in
      March (444) and the lowest in February (351).The most frequent days were Mondays
      (805), and the least frequent Sundays (495). Three fifths of patients were from
      urban areas and the rest of them were from rural areas. Out of this number 2,382
      (50.7%) were males and 2.318 (49.3%) were females, of which 1.847 (77.6%) males
      and 1,894 (81.7%) females were over 70 years old. The average number of
      hospitalization days was 12.29 days, and most patients were in hospital for less
      than 10 days (2101 patients). 4,130 (87.9%) patients were diagnosed with
      thromboembolism, 422 (9.0%) with intracerebral hemorrhage and 148 (3.2%) with
      subarachnoid hemorrhage. As an additional diagnosis 1,946 (41.4%) patients had
      hypertension, 867(18.6%) had heart insufficiency and 15.40% had diabetes. Most
      strokes with significant correlation were in biometheorological phases 9 and 4
      (1,227 and 1,010 strokes) and the least were in phase 10 (29). As a daily
      average, the highest number of strokes was in phase 8 (2.76/ day), the lowest in
      phase 2 (2.33/day). CONCLUSIONS: Biometeorological phases have a great influence
      on stroke incidence, especially in phases with stable sunny weather and sudden
      impact of weather fronts, with sudden weather changes, with average incidence in
      the phase of foggy weather.

PMID- 21849945
TI  - Quality of life in women with urinary incontinence.
AB  - AIM: To determine the characteristics of urinary incontinence and its impact on
      the quality of life in adult women with urinary incontinence who presented to a
      tertiary care clinic of Vojvodina from September 2008 to May 2009 for treatment
      METHODS: We used a prospective case-control study. Cases were defined as patients
      (47) with urinary incontinence symptoms. Controls (50) were defined as patients
      without urinary incontinence who presented to a tertiary care gynecology clinic
      for other reasons. Both, cases and controls, completed two questionnaires
      recommended for the evaluation of symptoms, The Urinary Distress Inventory, and
      quality of life impact The Urinary Impact Questionnaire. RESULTS: There was a
      significant correlation between aging (r=0.614; p<0.01), body mass index
      (r=0.357; p<0.01) and menopause (r= -0.572; p<0.01) and urinary incontinence. All
      patients had symptoms of stress incontinence, 61.7% had urge incontinence
      symptoms, 21.3% voiding difficulty and 85.1% dysuria. Ninety-four patients
      believed that urinary incontinence impaired their quality of life: 50% of
      patients reported an impaired ability to do household activities, 59.1% avoided
      social activities, 70.4% reported an impaired ability to travel more than 30
      minutes by car or bus, 88.6% avoided leisure activities, 45.5% of patients had
      impaired emotional health and 34% felt frustrated. CONCLUSIONS: The dominant type
      of urinary incontinence in more than half of the respondents was a mixed type,
      with moderate to very severe problems. Symptoms of urinary incontinence interfere
      with the performance of everyday household and social activities, causing the
      appearance of anxiety, depression and frustration, and in more than 50% of women
      leads to reduced quality of life.

PMID- 21849946
TI  - Postoperative pain in open vs. laparoscopic cholecystectomy with and without
      local application of anaesthetic.
AB  - AIM: To evaluate the intensity of postoperative pain and benefits of laparoscopic
      cholecystectomy compared to open cholecystectomy especially after anaesthetic
      infiltration of surgical incision. METHODS: This prospective cohort study
      included three groups of 30 patients each, who had undergone surgical treatment
      by an open procedure, by laparoscopic technique and by laparoscopic technique
      with local anaesthetic application. All patients were of similar age, sex and ASA
      risk (American Society of Anaesthesiologists). Pain intensity was assessed seven
      times and its evaluation was performed using VAS (Visual Analogue Scale).
      RESULTS: Postoperative pain intensity was lower in patients operated by
      laparoscopic technique compared to the open method, measured on the VAS ,
      especially for the first and second measuring. This difference is pronounced
      throughout the entire postoperative period (p<0,001). The pain intensity was
      significantly lower in patients treated with local anaesthetic (p<0.05).
      CONCLUSIONS: Laparoscopic cholecystectomy should be preferred over open
      cholecystectomy with respect to the intensity of postoperative pain, particularly
      after the application of local anaesthetic.

PMID- 21849947
TI  - Morphometric changes of the lumbar intervertebral space following discectomy on
      one or two levels.
AB  - AIM: To investigate a potential difference in postoperative morphological changes
      of two-level lumbar disc surgery as compared to one level surgery. METHODS: The
      standard lateral radiographs of lumbar spine obtained preoperatively and
      postoperatively were used in the study . The morphological study included 60
      adult patients of both sexes who had undergone the surgery in the period 2002
      2006. The first group comprised patients operated on one level (L4/L5 and L5/
      S1), and the second included patients operated on two levels (L3/ L4/L5; L4/L5/S1
      and L5/S1/S2). Using lateral radiographs, after digitalization, the height of
      intervertebral disc space (HD), angle between vertebral bodies (A) and
      translation (T) were measured. RESULTS: Comparing preoperative and postoperative
      values, statistically significant difference has been found for HD in the first
      group and HD and A in the second group. In neither groups there was statistically
      significant difference for T, which is one of radiological signs of segmental
      instability. The comparison of postoperative values for both groups has not shown
      any statistically significant difference. CONCLUSIONS: The standard lumbar
      discectomy on two levels has not shown more pronounced morphological changes or
      changes suggesting an increased risk of segmental instability as compared to one
      level discectomy.

PMID- 21849948
TI  - A better level of HbA1c control achieved by family medicine teams, Bosnia and
      Herzegovina, by using diabetes mellitus type 2 recommended guidelines.
AB  - AIM: To evaluate HbA1c level for diabetic type 2 patients after the
      implementation of guidelines for diabetes mellitus (GDM) in primary health care
      settings. According to recommendations of the European Society of Cardiology and
      European Association for the Study of Diabetes, HbA1c <= 6.5 % is considered as
      optimal level. METHODS: A retrospective analysis randomly selected medical
      records of DM type 2 patients who were older than 18 before and after the review.
      Nineteen Family Medicine Teams (FMT) reviewed every second record (46 per FMT) in
      the family medicine facilities in Zenica two years prior and after the
      introduction of the Diabetes Mellitus 2 Guidelines. All noted values of HbA1c and
      all FMTs have been divided to those which reached an optimal level of HbA1c <=
      6.5 % and those with an inadequate level (non-optimal level of HbA1c p< 6.5 %).
      RESULTS: Records of 853 patients with type 2 diabetes were analyzed. A total
      number of HbA1c recorded in the FMT medical records increased significantly after
      the GDM implementation from 103 (12.1%) to 318 (37.3%). A significant improvement
      towards an optimal level of HbA1c was noted after the implementation GDM by all
      FMTs together (7 vs. 92; 6.7% vs. 28.9%; p<0.0001). Only FMT 4 and FMT 14 (2
      vs.19; P < 0.05) reached the optimal level of HbA1c. CONCLUSIONS: Family medicine
      teams improved the level of HbA1c according to the recommended guidelines for
      diabetes mellitus after their application. Quality variations of care extended to
      diabetics have been noted in individual family medicine teams.

PMID- 21849949
TI  - Significant influence of biometeorological conditions on the incidence of
      spontaneous pneumothorax in the Kragujevac city.
AB  - AIM: To explore and establish an influence of biometeorological conditions on the
      occurrence of spontaneous pneumothorax (SP) in the city of Kragujevac (Serbia) in
      a five-year period. METHODS: According to the type of series of cases, this was a
      retrospective, non-interventional study. The data collected from the medical
      records and operative protocols of the Thoracic Surgery Department in the period
      between 01.01.2005 and 31.12.2009, as well as the data on daily biometeorological
      phases for the Kragujevac city obtained from the Hydrometeorological Service of
      Serbia, and afterwards a comparative analysis of the data were performed.
      RESULTS: A total number of 159 patients with spontaneous pneumothorax were
      hospitalized. Most patients were treated in 2009 (55, 34.6%), least in 2005 (22,
      13.8%). Most cases occurred in March (20, 12.6%), on Tuesdays (33, 20.7%), and in
      the biometeorological phase 2 (0.15 SP/day). The least number of cases occurred
      in September (9, 5.7%), on Saturdays (6, 3.8%) and in phase 8 (0.04/day)
      (p<0.01). CONCLUSIONS: There was an evident biometeorological influence on the
      occurrence of spontaneous pneumothorax in our area, so most cases were in the
      phase with sunny weather (atmospheric pressure falling, air temperature and
      moisture rising), while the lowest number was in the phase with a fall of
      atmospheric pressure, moisture and air temperature. The results of this research
      suggest a necessity of further investigations on this field.

PMID- 21849950
TI  - Smoking and asthma in children.
AB  - AIM: To investigate a possible association of asthma prevalence in schoolchildren
      aged 7-14 years in relation to their tobacco smoke exposure. METHODS: Case
      control study was realized at the Public Health Centre in the City of Novi Sad,
      the Province of Vojvodina, Republic of Serbia, between 2003 and 2005 and included
      504 participants. The study explored the relation between asthma in children and
      tobacco smoke exposure during pregnancy, the first year of life and/or onwards.
      The reports on smoking exposure were obtained by a questionnaire. RESULTS: The
      cases comprised 252 schoolchildren with asthma confirmed by the specialist. The
      controls (n=252) were respectively matched by age, gender and place of residence,
      selected from children's classmates, without any diagnostic or anamnestic records
      of asthma. Multivariate logistic regression analysis identified one positive
      characteristic associated with asthma occurrence in children - current
      environmental tobacco smoke exposure by persons other than parents (p=0.0132).
      CONCLUSIONS: The smoking habit has an influence on risk factors for the
      development of asthma in childhood and indicates a need of deeper understanding
      of lifestyle in asthma occurrence in children.

PMID- 21849951
TI  - Usage of insecure E-mail services among researchers with different scientific
      background.
AB  - AIM: Free web-based e-mail services are considered to have more security flaws
      than institutional ones, but they are frequently used among scientific
      researchers for professional communication. The aim of this study was to analyze
      frequency of usage of the insecure free e-mail services for professional
      communication among biomedical, economical and technical researchers, who
      published papers in one of three different journals: Croatian Medical Journal,
      Automatika and Economic Research. METHODS: Contact details of the authors who
      provided their e-mail address from the papers published in those three journals
      during one year period were collected. These e-mail addresses were collected from
      the electronic archive of the journals in question. The domains of all e-mail
      addresses were assessed and contacts were categorized into three groups according
      to the following types: world-wide known free web-based e-mail services, national
      Internet Service Provider (ISP) e-mail services, and institutional or corporate e
      mail addresses. RESULTS: The proportion of authors using free web-based e-mail
      services, the least secure group type, was highest among biomedical researchers
      (17.8%) while every e-mail address collected from the technical journal belonged
      to the secured institutional e-mail group type. CONCLUSIONS: It seems that all
      researchers from the technical scientific field and most of the researchers from
      the economical field value good security practice and use more secure systems for
      professional communication. High percentage of the biomedical researchers who use
      insecure e-mail services may mean that they need to be warned of the possible
      security disadvantages of those kinds of e-mail addresses.

PMID- 21849952
TI  - Clinical characteristics of nosocomial infections of patients with acute central
      nervous system infections treated in ICU.
AB  - A retrospective study was performed to evaluate the clinical characteristics of
      nosocomial infections in patients with acute infection of central nervous system
      (ACNS infections). The study included 1,686 patients admitted to the ICU. Of
      1,686 patients, 936 (55.5%) had ACNS infection. Nosocomial infections was
      confirmed in 221 (23.6%) patients with ACNS infection. The most common risk
      factors for ICU-acquired nosocomial infections were consciousness disorder,
      mechanical ventilation and nasogastric tube. The coagulase - negative
      Staphylococcus aureus was the most frequent isolated pathogen (285 isolates,
      56.5%). Results suggest that a persistently high level of therapeutic activity
      and persistently depressed consciousness after the ICU admission are associated
      with the occurrence of hospital-acquired infection in critically ill patients
      hospitalized at a medical ICU.

PMID- 21849953
TI  - Characteristics of radiological changes in lungs during varicella zoster viral
      infection.
AB  - The objective of this research was to analyse the varicella patients' data in
      order to determine the following: general frequency of pneumopathies and types of
      lung changes according to X-ray presentation and the changes on the computed
      tomography. It examined 101 patients with the clinical presentation of varicella
      and some of the X-ray entities of varicella pneumopathies. Radiological
      techniques included chest X-ray and CT scans. Familiarity with clinical,
      laboratory and radiological characteristics of the disease may be of utmost
      importance for early recognition.

PMID- 21849954
TI  - Microbiology of the chronic suppurative otitis media.
AB  - The aim of the study was to determine aetiological agents of chronic suppurative
      inflammation of the middle ear and their susceptibility to antibiotics, which
      could lead to better therapeutic decisions and consequently avoidance of
      appearance of resistance to specific antibiotics. Most frequently isolated agents
      were Staphylococcus aureus (30.6%), Pseudomonas aeruginosa (22.4%), Klebsiella
      spp. (10.6%) and Proteus spp. (7.1%). None of the isolates were resistant to
      ciprofloxacin. High sensitivity rates to gentamycin were noted in Staphylococcus
      and Klebsiella isolates, and moderate ones in Pseudomonas and Proteus isolates.
      Pseudomonas spp. has shown low prevalence of resistance to third-generation
      cephalosporins, as well as to imipenem and piperacillin.

PMID- 21849955
TI  - Ear injuries caused by parts of hearing aid.
AB  - This paper presents two cases of ear injuries caused by parts of hearing aids -a
      five-year old girl whose tympanic membrane was ruptured by a metal part of the
      earmold, and a patient with injury and inflammation of outer auditory channel
      caused by parts of a channel hearing aid. Aid amplifier could serve its purpose
      only if it is applied and handled with direct coordination with an ORL
      specialist.

PMID- 21849956
TI  - Surgical treatment of large smooth muscle tumor of uncertain malignant potential
      during pregnancy.
AB  - This paper presents a case of a 37-year old pregnant woman with a large tumor
      extending from pelvis to xyphoid, diagnosed at 14 weeks of pregnancy. At 18 weeks
      myomectomy was performed and the tumor weighing 4250 g was removed.
      Hystopathological findings showed a uterine smooth muscle tumour of uncertain
      malignant potential. Due to preeclampsia an urgent caesarean section was
      performed at 34 weeks of gestational age. A live and healthy female neonate was
      delivered. According to hystopathological findings and in agreement with the
      patient hysterectomy without adnexectomy was performed in the same act.

PMID- 21849957
TI  - Does massive cerebral venous thrombosis mean poor outcome?
AB  - A 21-year-old woman taking oral contraceptives presented with headaches, nausea,
      vomiting and somnolence. The next day she had a generalized tonic-clonic seizure
      after which her neurological condition deteriorated. CT and MRI showed multiple
      cerebral haemorrhages, while MR venography revealed extensive dural sinus and
      venous thrombosis involving almost all sinuses, great cerebral vein of Galen and
      internal cerebral veins. Two weeks after initiation of the anticoagulant
      treatment the patient recovered completely with complete recanalization of all
      cerebral sinuses and veins. Although the patient had conditions which were
      indicative of poor outcome, her neurological deficit improved completely, which
      correlated with recanalization of the thrombosed vessels.

PMID- 21849958
TI  - Basilar artery occlusion treated conventionally with good outcome.
AB  - It presents a case of a 39-year old woman with acute symptomatic occlusion of
      basilar artery proximal segment, which was manifested by severe neurological
      symptomatology and deficits. The patient was treated conventionally
      (anticoagulant, then antiplatelet agent therapy) with excellent short-term and
      long-term outcome. In spite of serious acute neurological symptomatology of
      basilar artery occlusion, proximal localization of the occlusion, fluctuating
      symptomatology flow, younger age and development of collateral circulation can
      suggest a good outcome in conventionally treated patients.

PMID- 21849959
TI  - Differential diagnosis of acute abdominal pain - acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder of heme
      biosynthesis in liver due to deficiency of porphobilinogen deaminase enzyme.
      Clinically, AIP is dominated by a colicky type pain, which does not subside after
      taking usual analgesics. Additional frequent symptoms are vomiting, hypertension,
      peripheral neuropathy, seizures, depression, delirium and coma. This paper
      reported a case of a twenty-five- year-old female patient, who had undergone a
      period of six days between the first presentation to the medical department and
      the diagnosis confirmation. It has accentuated possible mistakes in symptomatic
      therapy administration as well as dangers of a delayed diagnosis.

PMID- 21849960
TI  - Thrombosis of the internal jugular vein after tympanoplasty caused by interaction
      of oral contraceptives and hereditary hypofibrinolysis.
AB  - This case report describes a case of venous thrombosis in a young woman who had
      undergone tympanoplasty due to chronic otitis media. Other than that she was
      healthy. According to the anamnesis she stopped taking oral contraceptive pills
      (OCP) a month before the surgery. She did not receive thromboprophylaxis before
      the surgery because it was estimated that there was a low risk for a
      thromboembolic incident. Several hours after the surgery she was still not
      responding properly to external stimulus and there was no verbal contact. An
      urgent computed tomography (CT) scan of head and neck revealed thrombosis of the
      left internal jugular vein. She was admitted to the Intensive Care Unit (ICU) and
      heparin therapy started. After a few days she was fully recovered. Later it was
      confirmed that the patient had an inherited fibrinolysis disorder caused by
      plasminogen activator inhibitor 1 (PAI-1) gene polymorphism. Our opinion is that
      the unexpected thrombotic incident was a result of interaction of multiple
      factors, including the venous stasis at the surgery site, decreased fibrinolysis
      ability, and the prothrombotic effect of OCP.

PMID- 21849961
TI  - Impressive results of teriparatide treatment of postgastrectomy osteoporosis.
AB  - Patients who have undergone gastrectomy have a higher incidence of osteoporosis.
      We are presenting a patient with postgastrectomy osteoporosis who had been
      treated with multiple medications, including bisphosphonates, calcitriol and
      calcium, but with unsatisfactory results, low quality of life and a high risk of
      further fractures. However, after a treatment with teriparatide, a recombinant
      form of endogenous parathyroid hormone, the patient's bone mineral density
      increased considerably, with a substantial improvement of mobility and general
      condition. Since there do not seem to be specific any guidelines or
      recommendations for treating osteoporosis in postgastrectomy patients, our report
      may be very relevant for clinicians.

PMID- 21849962
TI  - Failure in long-term treatment of chronic pain in cervical spondylotic
      myelopathy.
AB  - Cervical spondylotic myelopathy is a disease of high variability and its
      progressive form leads to severe disability. This paper reports on a case of a 31
      year-old woman with whiplash neck injury sustained at the age of 11, and
      subsequent neck pain and numbness of arms. Slow progression of symptoms led to
      tetraparesis, and C3C4 disc herniation along with cervical myelopathy were
      revealed at the age of 26. Previously, she started a treatment for
      hypothyroidism. She underwent anterior cervical discectomy and fusion. Two
      additional operative treatments were done during the next two years due to lack
      of clinical improvement. Because of chronic pain the number of medications and
      the number of symptoms have gradually increased. We emphasize the problem of long
      term treatment for chronic non-malignant pain and therapeutic dilemma in
      situations of inadequate analgesia.

PMID- 21849963
TI  - Influenza vaccination coverage among health-care personnel --- United States,
      2010-11 influenza season.
AB  - The Advisory Committee on Immunization Practices (ACIP) and the Healthcare
      Infection Control Practices Advisory Committee recommend that all U.S. health
      care personnel (HCP) be vaccinated annually against influenza. Nonetheless,
      influenza vaccination coverage among HCP in the United States has increased
      slowly over the past decade; during the 2009-10 influenza season, 61.9% of HCP
      received seasonal influenza vaccination. To update data with estimates from the
      2010-11 influenza season, CDC conducted an Internet-based survey of 1,931 HCP who
      participated in three online survey panels. This report summarizes the results of
      that survey, which indicated that overall influenza vaccination coverage among
      HCP was 63.5% during the 2010--11 influenza season, similar to coverage for the
      2009-10 season. Among HCP who reported working at a facility where vaccination
      was required by their employer, 98.1% were vaccinated. Among HCP without such an
      employer requirement but who were offered vaccination onsite, greater coverage
      was associated with a personal reminder from the employer to get vaccinated
      (69.9%), vaccination availability at no cost (67.9%), and vaccination
      availability for >1 day (68.8%). Influenza vaccination of HCP is needed to
      protect patients from HCP-transmitted disease. Maximizing influenza vaccination
      for all HCP is an important part of any comprehensive infection-control program.

PMID- 21849964
TI  - Influenza vaccination coverage among pregnant women --- United States, 2010-11
      influenza season.
AB  - Women are at increased risk for morbidity and mortality from influenza during
      pregnancy. Vaccinating pregnant women for influenza can protect both the women
      and their infants, especially infants aged <6 months who are not old enough to
      receive influenza vaccination. Since 2004, the Advisory Committee on Immunization
      Practices and the American College of Obstetricians and Gynecologists have
      recommended inactivated influenza vaccine for all women who are pregnant during
      influenza season, regardless of trimester. Before 2009, estimated influenza
      vaccination coverage among pregnant women had been consistently low
      (approximately 15%). However, vaccination levels increased substantially in
      response to the 2009 influenza A (H1N1) pandemic to nearly 50%. To estimate
      influenza vaccination coverage among pregnant women for the 2010-11 season, CDC
      analyzed data from an Internet panel survey conducted in April 2011 among women
      who were pregnant any time during October 2010-January 2011. Among 1,457 survey
      respondents, 49% reported that they had received influenza vaccination: 12% were
      vaccinated before pregnancy, 32% during pregnancy, and 5% after pregnancy. Women
      offered influenza vaccination by a health-care provider (62%) were more likely to
      be vaccinated (71%) than other women (14%) and were more likely to have positive
      attitudes about vaccine effectiveness and safety. These results indicate that the
      higher vaccination level achieved the previous season (2009-10) was sustained and
      emphasize the critical role of health-care providers in promoting influenza
      vaccination. Continued efforts are needed to encourage health-care providers to
      strongly recommend and offer influenza vaccination to pregnant patients to
      protect both the mothers and their infants.

PMID- 21849965
TI  - Legionellosis --- United States, 2000-2009.
AB  - Legionnaires disease (LD), a serious, sometimes lethal pneumonia, and Pontiac
      fever (PF), an influenza-like, self-limited illness, are the two most common
      forms of legionellosis, which is caused by Legionella bacteria. Legionellosis
      cases are reported to CDC through the National Notifiable Disease Surveillance
      System (NNDSS) and a Supplemental Legionnaires Disease Surveillance System
      (SLDSS) designed to manage surveillance data on travel-related cases and enhance
      outbreak detection. For this report, cases reported to NNDSS during 2000-2009
      from the 50 states and the District of Columbia (DC) were assessed, and crude and
      age-adjusted incidence rates per 100,000 persons were calculated. U.S.
      legionellosis cases reported annually increased 217%, from 1,110 in 2000 to 3,522
      in 2009, and the crude national incidence rate increased 192%, from 0.39 per
      100,000 persons in 2000 to 1.15 in 2009. Because NNDSS is a passive surveillance
      system dependent on health-care providers and laboratories reporting cases, the
      actual incidence of legionellosis in the United States likely is higher. Although
      NNDSS does not record legionellosis cases by type, 99.5% of the legionellosis
      cases reported to SLDSS during 2005-2009 were classified as LD and 0.5% as PF.
      Legionellosis surveillance was added to the population-based Active Bacterial
      Core surveillance (ABCs) system in January 2011 to assess reasons for these
      increases in numbers of reported cases. The rise in reported cases reinforces the
      need for health-care providers in all parts of the United States to test and
      treat adults with severe community-acquired pneumonia for LD, to be vigilant for
      health-care--associated LD, and to report legionellosis cases to public health
      authorities.

PMID- 21849966
TI  - Notes from the field: transplant-transmitted hepatitis B virus --- United States,
      2010.
AB  - On March 29, 2011, CDC was notified about a possible transplant-associated
      hepatitis B virus (HBV) infection in a liver transplant recipient with no known
      risk factors for HBV infection. An investigation was begun to learn if other
      recipients of organs or tissues from the donor had been infected with HBV and to
      investigate potential sources of the donor's infection.

PMID- 21849967
TI  - Surveillance of certain health behaviors and conditions among states and selected
      local areas --- Behavioral Risk Factor Surveillance System, United States, 2009.
AB  - PROBLEM: Chronic diseases and conditions (e.g., heart disease, cancer, stroke,
      and diabetes) are the leading causes of death in the United States. Controlling
      health risk behaviors and conditions (e.g., smoking, physical inactivity, poor
      diet, excessive drinking, and obesity) and using preventive health-care services
      (e.g., physical examination, vaccination, screening for high blood pressure and
      high cholesterol, consumption of fruits and vegetables, and participation in
      regular leisure-time physical activity) can reduce morbidity and mortality from
      chronic diseases. REPORTING PERIOD: January 2009--December 2009. DESCRIPTION OF
      THE SYSTEM: The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing
      state-based random-digit--dialed telephone survey of noninstitutionalized adults
      aged >=18 years residing in the United States. BRFSS collects data on health risk
      behaviors and conditions, chronic diseases and conditions, access to health care,
      and use of preventative health services and practices related to the leading
      causes of death and disabilities in the United States. This report presents
      results for 2009 for all 50 states, the District of Columbia, the Commonwealth of
      Puerto Rico, Guam, the U.S. Virgin Islands, 180 metropolitan and micropolitan
      statistical areas (MMSAs), and 283 selected counties. RESULTS: In 2009, the
      estimated prevalence of general health status, use of preventive health-care
      services, health risk behaviors and conditions, chronic diseases, and health
      impairments and disabilities varied substantially by state and territory, MMSA,
      and county. The following is a summary of results listed by BRFSS question
      topics. Each set of proportions refers to the range of estimated prevalence for
      the disease, condition, or behavior, as reported by the survey respondent. Adults
      who reported having fair or poor health: 10.1%--30.9% for states and territories,
      7.9%--25.8% for MMSAs, and 4.5%--26.1% for counties. Adults with health-care
      coverage: 71.4%--94.7% for states and territories, 52.7%--96.3% for MMSAs, and
      52.7%--97.6% for counties. Annual routine physical checkup among adults aged >=18
      years: 55.8%--79.3% for states and territories, 51.8%--80.7% for MMSAs, and 49.2%
      -83.5% for counties. Annual influenza vaccination among adults aged >=65 years:
      26.8%--76.8% for states and territories, 55.4%--81.4% for MMSAs, and 50.5%--83.5%
      for counties. Pneumococcal vaccination among adults aged >=65 years: 19.1%--73.9%
      for states and territories, 52.9%--81.3% for MMSAs, and 41.9%--82.0% for
      counties. Adults who had their cholesterol checked within the preceding 5 years:
      67.5%--85.3% for states and territories, 58.2%--88.8% for MMSAs, and 58.2%--92.4%
      for counties. Adults who consumed at least five servings of fruits and vegetables
      per day: 14.6%--31.5% for states and territories, 12.6%--33.0% for MMSAs, and
      13.4%--34.9% for counties. Adults who engaged in moderate or vigorous physical
      activity: 28.0%--60.7% for states and territories, 34.6%--64.9% for MMSAs, and
      33.6%--67.3% for counties. Adults who engaged in only vigorous physical activity:
      13.7%--40.1% for states and territories, 13.8%--43.3% for MMSAs, and 14.2%--50.0%
      for counties. Current cigarette smoking among adults: 6.4%--25.6% for states and
      territories, 5.7%--29.0% for MMSAs, and 5.6%--29.8% for counties. Binge drinking
      among adults: 6.8%--23.9% for states and territories, 3.5%--23.2% for MMSAs, and
      3.4%--26.3% for counties. Heavy drinking among adults: 1.9%--8.1% for states and
      territories, 1.0%--11.1% for MMSAs, and 0.9%--11.1% for counties. Adults who
      reported no leisure-time physical activity: 15.8%--45.6% for states and
      territories, 13.3%--40.2% for MMSAs, and 10.5%--40.2% for counties. Adults aged
      >=18 years who were overweight: 31.6%--38.7% for states and territories, 28.7%-
      44.1% for MMSAs, and 25.6%--46.7% for counties. Adults aged >=20 years who were
      obese: 19.7%--36.0% for states and territories, 15.4%--43.6% for MMSAs, and 13.8%
      -45.7% for counties. Adults aged >=18 years who did not get enough rest or sleep:
      34.3%--52.6% for states and territories, 28.2%--54.8% for MMSAs, and 24.5%--55.6%
      for counties. Adults who had received a high blood pressure diagnosis: 22.1%-
      38.5% for states and territories, 18.8%--43.9% for MMSAs, and 17.2%--43.6% for
      counties. Adults who had a high blood cholesterol diagnosis: 24.9%--42.2% for
      states and territories, 27.5%--47.8% for MMSAs, and 26.7%--51.4% for counties.
      Adults who had received a diagnosis of coronary heart disease: 2.5%--10.3% for
      states and territories, 2.6%--11.6% for MMSAs, and 1.6%--12.3% for counties.
      Adults who had received a stroke diagnosis: 1.4%--3.9% for states and
      territories, 0.8%--5.9% for MMSAs, and 0.8%--6.6% for counties. Adults who had
      received a diabetes diagnosis: 5.8%--12.9% for states and territories, 2.8%-
      15.4% for MMSAs, and 2.8%--14.7% for counties. Adults who had received a cancer
      diagnosis: 3.0%--12.6% for states and territories, 5.8%--15.1% for MMSAs, and
      3.9%--16.2% for counties. Adults who had asthma: 4.4%--11.1% for states and
      territories, and 3.2%--15.3% for MMSAs, and 3.2%--15.7% for counties. Adults who
      had arthritis: 10.7%--35.6% for states and territories, 16.2%--36.0% for MMSAs,
      and 12.6%--39.4% for counties. Adults with activity limitation associated with
      physical, mental, or emotional problems: 10.2%--27.1% for states and territories,
      13.1%--33.7% for MMSAs, and 10.4%--36.1% for counties. Adults who required
      special equipment because of health problems: 3.6%--10.2% for states and
      territories, 3.4%--11.5% for MMSAs, and 1.7%--13.0% for counties. INTERPRETATION:
      The findings in this report indicate substantial variations in self-rated general
      health status, health-care coverage, use of preventive health-care services,
      health risk behaviors and health conditions, cardiovascular conditions, other
      chronic diseases, and health impairments and disabilities among U.S. adults at
      the state and territory, MMSA, and county levels. The findings show that Healthy
      People 2010 objectives had not been met in many areas by 2009, which underscores
      the continued need for surveillance of general health status, use of preventive
      health-care services, health risk behaviors and conditions, chronic diseases, and
      health impairment and disability. PUBLIC HEALTH ACTION: Data on health risk
      behaviors, chronic health conditions, preventive care practices, and chronic
      diseases are used to develop health promotion activities, intervention programs,
      and health policies at the state, city, and county levels.. The overarching goals
      of Healthy People 2010 are to increase quality and years of healthy life and to
      eliminate health disparities. Local and state health departments and federal
      agencies should continue to use BRFSS data to identify populations at high risk
      for certain health risk behaviors and conditions, cardiovascular conditions, and
      other chronic diseases and to evaluate the use of preventive health-care
      services. In addition, BRFSS data can be used to direct, implement, monitor, and
      evaluate public health programs and policies that can lead to a reduction in
      morbidity and mortality.

PMID- 21849968
TI  - Sickle cell trait is not independently associated with susceptibility to end
      stage renal disease in African Americans.
AB  - Conflicting reports exist as to whether sickle cell trait is a risk factor for
      the progression of nephropathy. In order to determine whether African Americans
      with sickle cell trait are at increased risk for kidney disease, we assessed the
      genetic association between sickle cell trait and end-stage renal disease (ESRD).
      Hemoglobin S, non-muscle myosin heavy chain 9 (MYH9), and apolipoprotein L1
      (APOL1) risk variants were genotyped in 3258 unrelated African Americans: 1085
      with non-diabetic ESRD, 996 with type 2 diabetes-associated ESRD, and 1177
      controls. Since APOL1 is strongly associated with ESRD in African Americans,
      interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed
      using case-only and case-control centered two-way logistic regression interaction
      analyses. The sickle cell trait genotype frequencies were 8.7% in non-diabetic
      ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-,
      gender-, and admixture-adjusted significance for sickle cell trait association
      with non-diabetic ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01);
      or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients
      compared to the controls; odds ratio 1.05) in dominant models. In addition, no
      evidence of APOL1 or MYH9 interactions with sickle cell trait was detected.
      Hence, sickle cell trait is not associated with diabetic or non-diabetic ESRD in
      a large sample of African Americans.

PMID- 21849969
TI  - Sphingosine kinase 1 protects against renal ischemia-reperfusion injury in mice
      by sphingosine-1-phosphate1 receptor activation.
AB  - The roles of sphingosine kinases SK1 and SK2 in ischemia-reperfusion injury have
      not been fully elucidated since studies have found beneficial effects of SK1
      while others showed no role in this injury. To help resolve this, we used SK1 or
      SK2 knockout mice and confirmed that renal ischemia-reperfusion injury induced
      SK1, but not SK2, in the kidneys. Furthermore, knockout or pharmacological
      inhibition of SK1 increased injury after renal ischemia-reperfusion injury. In
      contrast, lack of SK2 conferred renal protection following injury. In addition,
      we used lentiviral gene delivery to selectively express enhanced green
      fluorescent protein (EGFP) or human SK1 coexpressed with EGFP (EGFP-huSK1) in the
      kidney. Mice with kidney-specific overexpression of EGFP-huSK1 had significantly
      improved renal function with lower plasma creatinine, renal necrosis, apoptosis,
      and inflammation. Moreover, EGFP-huSK1 overexpression in cultured human proximal
      tubule (HK-2) cells protected against peroxide-induced necrosis. Selective
      overexpression of EGFP-huSK1 led to increased HSP27 mRNA and protein expression
      in vivo and in vitro. Functional protection as well as induction of HSP27 with
      EGFP-huSK1 overexpression in vivo was blocked with sphingosine-1-phosphate-1
      receptor(1) (S1P(1)) antagonism. Thus, our findings suggest that SK1 is
      renoprotective by S1P(1) activation and perhaps HSP27 induction. Kidney-specific
      expression of SK1 through lentiviral delivery may be a viable therapeutic option
      to attenuate renal ischemia-reperfusion injury.

PMID- 21849970
TI  - Non-muscle myosin IIA is required for the development of the zebrafish
      glomerulus.
AB  - Mutations in the MYH9 gene, coding for the non-muscle myosin heavy chain IIA
      (NMHC-IIA), are responsible for syndromes characterized by macrothrombocytopenia
      associated with deafness, cataracts, and severe glomerular disease. Electron
      microscopy of renal biopsies from these patients found glomerular abnormalities
      characterized by alterations in mesangial cells, podocytes, and thickening of the
      glomerular basement membrane. Knockout of NMHC-IIA in mice is lethal, and
      therefore little is known about the glomerular-related functions of Myh9. Here,
      we use zebrafish as a model to study the role and function of zNMHC-IIA in the
      glomerulus. Knockdown of zNMHC-IIA resulted in malformation of the glomerular
      capillary tuft characterized by few and dilated capillaries of the pronephros. In
      zNMHC-IIA morphants, endothelial cells failed to develop fenestrations, mesangial
      cells were absent or reduced, and the glomerular basement membrane appeared
      nonuniformly thickened. Knockdown of zNMHC-IIA did not impair the formation of
      podocyte foot processes or slit diaphragms; however, podocyte processes were less
      uniform in these morphants compared to controls. In vivo clearance of fluorescent
      dextran indicated that the glomerular barrier function was not compromised by
      zNMHC-IIA knockdown; however, glomerular filtration was significantly reduced.
      Thus, our results demonstrate an important role of zNMHC-IIA for the proper
      formation and function of the glomerulus in zebrafish.

PMID- 21849971
TI  - Higher estimated glomerular filtration rates may be associated with increased
      risk of adverse outcomes, especially with concomitant proteinuria.
AB  - The estimated glomerular filtration rate (eGFR) is a powerful predictor of
      adverse outcomes, but most attention has focused on studies in the setting of
      reduced eGFR. Here we tested whether patients with an eGFR higher than 60-89.9
      ml/min per 1.73 m(2) could also be at elevated risk of adverse outcomes. Further,
      we tested whether concomitant proteinuria further increases the risk of outcomes
      among individuals with an eGFR equal to or above 90 ml/min per 1.73 m(2), as it
      does for those with reduced eGFR. Using data from a population-based outpatient
      laboratory data set of 1,526,437 patients, we measured adjusted associations
      between eGFR calculated by the modification of diet in renal disease equation,
      urine dipstick proteinuria, and adverse clinical outcomes. The adjusted risk of
      all-cause mortality was lowest at an eGFR of 60-74.9 ml/min per 1.73 m(2)
      (referent) and increased at both lower and higher levels of eGFR. Specifically,
      the hazard ratio of death was 3.7 and 1.8 among patients with an eGFR equal to or
      above 105 and 90-104.9 ml/min per 1.73 m(2), respectively, compared to the
      referent group. Similar results were seen when the CKD-EPI equation (sensitivity
      analyses) was used to assess eGFR. Higher levels of eGFR were not associated with
      the risk of kidney failure or myocardial infarction. Thus, the presence and
      severity of proteinuria was significantly associated with graded increases in the
      risk of clinical outcomes for both lower and higher eGFR. We do not know,
      however, whether the finding at higher eGFR could be due to inadequacies of the
      eGFR formula at low serum creatinine levels.

PMID- 21849973
TI  - Selective albuminuria via podocyte albumin transport in puromycin nephrotic rats
      is attenuated by an inhibitor of NADPH oxidase.
AB  - The mechanism of selective albuminuria in minimal change nephrotic syndrome, in
      which glomerular capillaries are diffusely covered by effaced podocyte foot
      processes with reduced slit diaphragms, is unknown. Podocyte injury is due, in
      part, to NADPH-induced oxidative stress. Here we studied mechanism of selective
      albuminuria in puromycin aminonucleoside (PAN) nephrotic rats, a model of minimal
      change nephrotic syndrome. In these rats, Evans Blue-labeled human albumin was
      taken up by podocytes and its urinary excretion markedly increased, with retained
      selectivity for albumin. Immunogold scanning electron micrographic images found
      increased human albumin in podocyte vesicles and on the apical membrane in
      nephrotic compared with control rats. Apocynin, an inhibitor of NADPH oxidase,
      decreased superoxide production in podocytes, and inhibited endocytosis and
      urinary albumin excretion. Real-time confocal microscopy found an initial delay
      in the appearance of Evans Blue-labeled human albumin in the tubular lumen,
      reflecting the time needed for transcellular transport. Immunoprecipitation
      analysis indicated that FcRn, a receptor for albumin transport, mediated podocyte
      albumin transport, and treatment with anti-FcRn antibody reduced proteinuria in
      these nephrotic rats. Thus, podocyte albumin transport was enhanced in PAN
      nephrotic rats by means of FcRn, which may explain the mechanism of selective
      proteinuria. This was blocked by apocynin, suggesting a new therapeutic approach.

PMID- 21849972
TI  - Variant hemoglobin phenotypes may account for differential erythropoiesis
      stimulating agent dosing in African-American hemodialysis patients.
AB  - African-American patients with end-stage renal disease have historically lower
      hemoglobin concentrations and higher requirements of erythropoiesis-stimulating
      agent (ESA). While disparities in health-care access may partially explain these
      findings, the role of variant hemoglobin, such as sickle trait, has not been
      investigated. To clarify this, we evaluated 154 African-American patients
      receiving in-center hemodialysis with available hemoglobin phenotyping. The
      primary exposure was any abnormal hemoglobin variant and the primary outcome of
      higher-dose ESA was defined as a dose of 6500 or more units per treatment.
      Logistic regression assessed the association between variant hemoglobin and
      higher-dose ESA. Covariates included age, gender, diabetes, iron parameters,
      intravenous iron dose, parathyroid hormone, albumin, phosphorus, body mass index,
      vascular access type, hospitalization/missed treatments, smoking status, alcohol
      abuse, and gastrointestinal bleeding. Of 33 patients with variant hemoglobin, 24
      had HbAS and 9 had HbAC. Univariate odds of higher-dose ESA among those with
      hemoglobin variants were twice that of those with the normal HbAA phenotype (odds
      ratio 2.05). In multivariate models, the likelihood of higher-dose ESA had an
      odds ratio of 3.31 and the nature of this relationship did not change in Poisson
      regression or sensitivity analyses. Hence, our findings may explain, in part, the
      difference in ESA dosing between Caucasians and African-Americans with end-stage
      renal disease but await further study.

PMID- 21849974
TI  - Chronological evidence that the Moon is either young or did not have a global
      magma ocean.
AB  - Chemical evolution of planetary bodies, ranging from asteroids to the large rocky
      planets, is thought to begin with differentiation through solidification of magma
      oceans many hundreds of kilometres in depth. The Earth's Moon is the archetypical
      example of this type of differentiation. Evidence for a lunar magma ocean is
      derived largely from the widespread distribution, compositional and mineralogical
      characteristics, and ancient ages inferred for the ferroan anorthosite (FAN)
      suite of lunar crustal rocks. The FANs are considered to be primary lunar
      flotation-cumulate crust that crystallized in the latter stages of magma ocean
      solidification. According to this theory, FANs represent the oldest lunar crustal
      rock type. Attempts to date this rock suite have yielded ambiguous results,
      however, because individual isochron measurements are typically incompatible with
      the geochemical make-up of the samples, and have not been confirmed by additional
      isotopic systems. By making improvements to the standard isotopic techniques, we
      report here the age of crystallization of FAN 60025 using the (207)Pb-(206)Pb,
      (147)Sm-(143)Nd and (146)Sm-(142)Nd isotopic systems to be 4,360 +/- 3 million
      years. This extraordinarily young age requires that either the Moon solidified
      significantly later than most previous estimates or the long-held assumption that
      FANs are flotation cumulates of a primordial magma ocean is incorrect. If the
      latter is correct, then much of the lunar crust may have been produced by non
      magma-ocean processes, such as serial magmatism.

PMID- 21849975
TI  - Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral
      therapy.
AB  - Latency and ongoing replication have both been proposed to explain the drug
      insensitive human immunodeficiency virus (HIV) reservoir maintained during
      antiretroviral therapy. Here we explore a novel mechanism for ongoing HIV
      replication in the face of antiretroviral drugs. We propose a model whereby
      multiple infections per cell lead to reduced sensitivity to drugs without
      requiring drug-resistant mutations, and experimentally validate the model using
      multiple infections per cell by cell-free HIV in the presence of the drug
      tenofovir. We then examine the drug sensitivity of cell-to-cell spread of HIV, a
      mode of HIV transmission that can lead to multiple infection events per target
      cell. Infections originating from cell-free virus decrease strongly in the
      presence of antiretrovirals tenofovir and efavirenz whereas infections involving
      cell-to-cell spread are markedly less sensitive to the drugs. The reduction in
      sensitivity is sufficient to keep multiple rounds of infection from terminating
      in the presence of drugs. We examine replication from cell-to-cell spread in the
      presence of clinical drug concentrations using a stochastic infection model and
      find that replication is intermittent, without substantial accumulation of
      mutations. If cell-to-cell spread has the same properties in vivo, it may have
      adverse consequences for the immune system, lead to therapy failure in
      individuals with risk factors, and potentially contribute to viral persistence
      and hence be a barrier to curing HIV infection.

PMID- 21849976
TI  - Parallel evolution of domesticated Caenorhabditis species targets pheromone
      receptor genes.
AB  - Evolution can follow predictable genetic trajectories, indicating that discrete
      environmental shifts can select for reproducible genetic changes. Conspecific
      individuals are an important feature of an animal's environment, and a potential
      source of selective pressures. Here we show that adaptation of two Caenorhabditis
      species to growth at high density, a feature common to domestic environments,
      occurs by reproducible genetic changes to pheromone receptor genes. Chemical
      communication through pheromones that accumulate during high-density growth
      causes young nematode larvae to enter the long-lived but non-reproductive dauer
      stage. Two strains of Caenorhabditis elegans grown at high density have
      independently acquired multigenic resistance to pheromone-induced dauer
      formation. In each strain, resistance to the pheromone ascaroside C3 results from
      a deletion that disrupts the adjacent chemoreceptor genes serpentine receptor
      class g (srg)-36 and -37. Through misexpression experiments, we show that these
      genes encode redundant G-protein-coupled receptors for ascaroside C3. Multigenic
      resistance to dauer formation has also arisen in high-density cultures of a
      different nematode species, Caenorhabditis briggsae, resulting in part from
      deletion of an srg gene paralogous to srg-36 and srg-37. These results
      demonstrate rapid remodelling of the chemoreceptor repertoire as an adaptation to
      specific environments, and indicate that parallel changes to a common genetic
      substrate can affect life-history traits across species.

PMID- 21849977
TI  - Broad neutralization coverage of HIV by multiple highly potent antibodies.
AB  - Broadly neutralizing antibodies against highly variable viral pathogens are much
      sought after to treat or protect against global circulating viruses. Here we
      probed the neutralizing antibody repertoires of four human immunodeficiency virus
      (HIV)-infected donors with remarkably broad and potent neutralizing responses and
      rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many
      of the new monoclonal antibodies are almost tenfold more potent than the recently
      described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100
      fold more potent than the original prototype HIV broadly neutralizing monoclonal
      antibodies. The monoclonal antibodies largely recapitulate the neutralization
      breadth found in the corresponding donor serum and many recognize novel epitopes
      on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine
      design. Analysis of neutralization by the full complement of anti-HIV broadly
      neutralizing monoclonal antibodies now available reveals that certain
      combinations of antibodies should offer markedly more favourable coverage of the
      enormous diversity of global circulating viruses than others and these
      combinations might be sought in active or passive immunization regimes. Overall,
      the isolation of multiple HIV broadly neutralizing monoclonal antibodies from
      several donors that, in aggregate, provide broad coverage at low concentrations
      is a highly positive indicator for the eventual design of an effective antibody
      based HIV vaccine.

PMID- 21849978
TI  - Haem oxygenase is synthetically lethal with the tumour suppressor fumarate
      hydratase.
AB  - Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle)
      that catalyses the hydration of fumarate into malate. Germline mutations of FH
      are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It
      has previously been demonstrated that the absence of FH leads to the accumulation
      of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen
      tensions. However, so far no mechanism that explains the ability of cells to
      survive without a functional TCA cycle has been provided. Here we use newly
      characterized genetically modified kidney mouse cells in which Fh1 has been
      deleted, and apply a newly developed computer model of the metabolism of these
      cells to predict and experimentally validate a linear metabolic pathway beginning
      with glutamine uptake and ending with bilirubin excretion from Fh1-deficient
      cells. This pathway, which involves the biosynthesis and degradation of haem,
      enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and
      permits partial mitochondrial NADH production. We predicted and confirmed that
      targeting this pathway would render Fh1-deficient cells non-viable, while sparing
      wild-type Fh1-containing cells. This work goes beyond identifying a metabolic
      pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of
      haem oxygenation is synthetically lethal when combined with Fh1 deficiency,
      providing a new potential target for treating HLRCC patients.

PMID- 21849979
TI  - Imaging drugs with and without clinical analgesic efficacy.
AB  - The behavioral response to pain is driven by sensory and affective components,
      each of which is mediated by the CNS. Subjective pain ratings are used as
      readouts when appraising potential analgesics; however, pain ratings alone cannot
      enable a characterization of CNS pain circuitry during pain processing or how
      this circuitry is modulated pharmacologically. Having a more objective readout of
      potential analgesic effects may allow improved understanding and detection of
      pharmacological efficacy for pain. The pharmacological/functional magnetic
      resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate
      drug action on the CNS. In this context, we aimed to evaluate two drugs that had
      been developed as analgesics: one that is efficacious for pain (buprenorphine
      (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP).
      Using phMRI, we observed that activation induced solely by BUP was present in
      regions with MU-opioid receptors, whereas APREP-induced activation was seen in
      regions expressing NK(1) receptors. However, significant pharmacological
      modulation of functional connectivity in pain-processing pathways was only
      observed following BUP administration. By implementing an evoked pain fMRI
      paradigm, these drugs could also be differentiated by comparing the respective
      fMRI signals in CNS circuits mediating sensory and affective components of pain.
      We report a correlation of functional connectivity and evoked pain fMRI measures
      with pain ratings as well as peak drug concentration. This investigation
      demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI
      methodology may be used with conventional measures to better evaluate candidate
      analgesics in small subject cohorts.

PMID- 21849980
TI  - Baseline brain metabolism in resistant depression and response to transcranial
      magnetic stimulation.
AB  - Neuroimaging studies of patients with treatment-resistant depression (TRD) have
      reported abnormalities in the frontal and temporal regions. We sought to
      determine whether metabolism in these regions might be related to response to
      repetitive transcranial magnetic stimulation (TMS) in patients with TRD. Magnetic
      resonance images and baseline resting-state cerebral glucose uptake index (gluMI)
      obtained using (18)F-fluorodeoxyglucose positron emission tomography were
      analyzed in TRD patients who had participated in a double-blind, randomized, sham
      controlled trial of prefrontal 10 Hz TMS. Among the patients randomized to active
      TMS, 17 responders, defined as having 50% depression score decrease, and 14
      nonresponders were investigated for prestimulation glucose metabolism and
      compared with 39 healthy subjects using a voxel-based analysis. In nonresponders
      relative to responders, gluMI was lower in left lateral orbitofrontal cortex
      (OFC), and higher in left amygdala and uncinate fasciculus. OFC and amygdala
      gluMI negatively correlated in nonresponders, positively correlated in
      responders, and did not correlate in healthy subjects. Relative to healthy
      subjects, both responders and nonresponders displayed lower gluMI in right
      dorsolateral prefrontal (DLPFC), right anterior cingulate (ACC), and left
      ventrolateral prefrontal cortices. Additionally, nonresponders had lower gluMI in
      left DLPFC, ACC, left and right insula, and higher gluMI in left amygdala and
      uncus. Hypometabolisms were partly explained by gray matter reductions, whereas
      hypermetabolisms were unrelated to structural changes. The findings suggest that
      different patterns of frontal-temporal-limbic abnormalities may distinguish
      responders and nonresponders to prefrontal magnetic stimulation. Both preserved
      OFC volume and amygdala metabolism might precondition response to TMS.

PMID- 21849981
TI  - Brain-cocaine concentrations determine the dose self-administered by rats on a
      novel behaviorally dependent dosing schedule.
AB  - A novel behaviorally dependent dosing (BDD) schedule was used to examine the
      relationship between doses of cocaine self-administered by rats and brain drug
      levels within a session. The BDD schedule used a hold-down response to activate a
      syringe pump. The length of time the lever was held down determined the duration
      that the syringe pump was activated. In the first experiment, rats self
      administered cocaine for daily 3 h sessions and brain levels of cocaine were
      modeled using well-established parameters. Although analysis revealed that rats
      self-administered doses within a predicted range, one extremely large dose was
      consistently observed at the beginning of each session when brain levels of
      cocaine were low. In the second experiment, we introduced a range of timeout
      periods (10-25 min) in order to produce variability in brain-cocaine
      concentrations. Animals self-administered larger doses immediately following each
      timeout period and the dose size was inversely correlated with the length of the
      timeout. These results show that the dose of cocaine that rats self-administer
      within a session is inversely related to the amount of drug on board.

PMID- 21849982
TI  - Age, sex, and reproductive hormone effects on brain serotonin-1A and serotonin-2A
      receptor binding in a healthy population.
AB  - There is a need for rigorous positron emission tomography (PET) and endocrine
      methods to address inconsistencies in the literature regarding age, sex, and
      reproductive hormone effects on central serotonin (5HT) 1A and 2A receptor
      binding potential (BP). Healthy subjects (n=71), aged 20-80 years, underwent
      5HT1A and 2A receptor imaging using consecutive 90-min PET acquisitions with
      [(11)C]WAY100635 and [(18)F]altanserin. Logan graphical analysis was used to
      derive BP using atrophy-corrected distribution volume (V(T)) in prefrontal,
      mesiotemporal, occipital cortices, and raphe nucleus (5HT1A only). We used
      multivariate linear regression modeling to examine BP relationships with age,
      age(2), sex, and hormone concentrations, with post hoc regional significance set
      at p<0.008. There were small postsynaptic 5HT1A receptor BP increases with age
      and estradiol concentration in women (p=0.004-0.005) and a tendency for small
      5HT1A receptor BP declines with age and free androgen index in men (p=0.05-0.06).
      Raphe 5HT1A receptor BP decreased 4.5% per decade of age (p=0.05), primarily in
      men. There was a trend for 15% receptor reductions in prefrontal cortical regions
      in women relative to men (post hoc p=0.03-0.10). The significant decline in 5HT2A
      receptor BP relative to age (8% per decade; p<0.001) was not related to sex or
      hormone concentrations. In conclusion, endocrine standardization minimized
      confounding introduced by endogenous hormonal fluctuations and reproductive stage
      and permitted us to detect small effects of sex, age, and endogenous sex steroid
      exposures upon 5HT1A binding. Reduced prefrontal cortical 5HT1A receptor BP in
      women vs men, but increased 5HT1A receptor BP with aging in women, may partially
      explain the increased susceptibility to affective disorders in women during their
      reproductive years that is mitigated in later life. 5HT1A receptor decreases with
      age in men might contribute to the known increased risk for suicide in men over
      age 75 years. Low hormone concentrations in adults <50 years of age may be
      associated with more extreme 5HT1A receptor BP values, but remains to be studied
      further. The 5HT2A receptor declines with age were not related to sex or hormone
      concentrations in this sample. Additional study in clinical populations is needed
      to further examine the affective role of sex-hormone-serotonin receptor
      relationships.

PMID- 21849983
TI  - Reversible gating of endocannabinoid plasticity in the amygdala by chronic
      stress: a potential role for monoacylglycerol lipase inhibition in the prevention
      of stress-induced behavioral adaptation.
AB  - Chronic stress is the primary environmental risk factor for the development and
      exacerbation of affective disorders, thus understanding the neuroadaptations that
      occur in response to stress is a critical step in the development of novel
      therapeutics for depressive and anxiety disorders. Brain endocannabinoid (eCB)
      signaling is known to modulate emotional behavior and stress responses, and
      levels of the eCB 2-arachidonoylglycerol (2-AG) are elevated in response to
      chronic homotypic stress exposure. However, the role of 2-AG in the synaptic and
      behavioral adaptations to chronic stress is poorly understood. Here, we show that
      stress-induced development of anxiety-like behavior is paralleled by a transient
      appearance of low-frequency stimulation-induced, 2-AG-mediated long-term
      depression at GABAergic synapses in the basolateral amygdala, a key region
      involved in motivation, affective regulation, and emotional learning. This
      enhancement of 2-AG signaling is mediated, in part, via downregulation of the
      primary 2-AG-degrading enzyme monoacylglycerol lipase (MAGL). Acute in vivo
      inhibition of MAGL had little effect on anxiety-related behaviors. However,
      chronic stress-induced anxiety-like behavior and emergence of long-term
      depression of GABAergic transmission was prevented by chronic MAGL inhibition,
      likely via an occlusive mechanism. These data indicate that chronic stress
      reversibly gates eCB synaptic plasticity at inhibitory synapses in the amygdala,
      and in vivo augmentation of 2-AG levels prevents both behavioral and synaptic
      adaptations to chronic stress.

PMID- 21849984
TI  - Laminin-beta1 impairs spatial learning through inhibition of ERK/MAPK and SGK1
      signaling.
AB  - Laminin is a major structural element of the basal lamina consisting of an alpha
      chain, a beta-chain, and a gamma-chain arranged in a cross-like structure, with
      their C-terminal inter-coiled. Laminin is abundantly expressed in the hippocampus
      of mature brain and is implicated in several psychiatric disorders, but its
      possible role involved in learning and memory function is not known. This issue
      was examined here. Our results revealed that water maze training significantly
      decreased laminin-beta1 (LB1) expression in the rat hippocampal CA1 area.
      Transfection of LB1 WT plasmid to hippocampal CA1 neurons impaired water maze
      performance in rats. Meanwhile, it decreased the phosphorylation level of
      ERK/MAPK and protein kinase serum- and glucocorticoid-inducible kinase-1 (SGK1).
      By contrast, knockdown of endogenous LB1 expression using RNA interference (LB1
      siRNA) enhanced water maze performance. Meanwhile, it increased the
      phosphorylation level of ERK/MAPK and SGK1. The enhancing effect of LB1 siRNA on
      spatial learning and on the phosphorylation of ERK/MAPK and SGK1 was blocked by
      co-treatment with the MEK inhibitor U0126 at a concentration that did not
      apparently affect spatial learning and ERK/MAPK phosphorylation alone. Further,
      the enhancing effect of LB1 siRNA on spatial learning and SGK1 phosphorylation
      was similarly blocked by co-transfection with SGK1 siRNA at a concentration that
      did not markedly affect spatial learning and SGK1 expression alone. These results
      together indicate that LB1 negatively regulates spatial learning in rats. In
      addition, LB1 impairs spatial learning through decreased activation of the
      ERK/MAPK-SGK1 signaling pathway in the rat hippocampus.

PMID- 21849986
TI  - Made to measure.

PMID- 21849985
TI  - A genomewide linkage scan of cocaine dependence and major depressive episode in
      two populations.
AB  - Cocaine dependence (CD) and major depressive episode (MDE) frequently co-occur
      with poorer treatment outcome and higher relapse risk. Shared genetic risk was
      affirmed; to date, there have been no reports of genomewide linkage scans (GWLSs)
      surveying the susceptibility regions for comorbid CD and MDE (CD-MDE). We aimed
      to identify chromosomal regions and candidate genes susceptible to CD, MDE, and
      CD-MDE in African Americans (AAs) and European Americans (EAs). A total of 1896
      individuals were recruited from 384 AA and 355 EA families, each with at least a
      sibling-pair with CD and/or opioid dependence. Array-based genotyping of about
      6000 single-nucleotide polymorphisms was completed for all individuals.
      Parametric and non-parametric genomewide linkage analyses were performed. We
      found a genomewide-significant linkage peak on chromosome 7 at 183.4 cM for non
      parametric analysis of CD-MDE in AAs (lod=3.8, genomewide empirical p=0.016;
      point-wise p=0.00001). A nearly genomewide significant linkage was identified for
      CD-MDE in EAs on chromosome 5 at 14.3 cM (logarithm of odds (lod)=2.95,
      genomewide empirical p=0.055; point-wise p=0.00012). Parametric analysis
      corroborated the findings in these two regions and improved the support for the
      peak on chromosome 5 so that it reached genomewide significance (heterogeneity
      lod=3.28, genomewide empirical p=0.046; point-wise p=0.00053). This is the first
      GWLS for CD-MDE. The genomewide significant linkage regions on chromosomes 5 and
      7 harbor four particularly promising candidate genes: SRD5A1, UBE3C, PTPRN2, and
      VIPR2. Replication of the linkage findings in other populations is warranted, as
      is a focused analysis of the genes located in the linkage regions implicated
      here.

PMID- 21849995
TI  - GPCRs: Caught in a spectroscopic trap.

PMID- 21849996
TI  - Biomaterials: Redox and adhesion on the rocks.

PMID- 21849997
TI  - Amyloidogenesis: FlAsH illuminates Abeta aggregation.

PMID- 21849998
TI  - Reaction design: Nature-inspired total synthesis.

PMID- 21850006
TI  - Blood pressure variability and its implications in people of African descent.

PMID- 21850007
TI  - Remapping and mutation analysis of benign adult familial myoclonic epilepsy in a
      Japanese pedigree.
AB  - Benign adult familial myoclonic epilepsy (BAFME), alternatively named familial
      adult myoclonic epilepsy 1/familial cortical myoclonic tremor with epilepsy 1
      (FAME1/FCMTE1), is a hereditary epileptic syndrome characterized by autosomal
      dominant inheritance, adult-onset tremulous hand movement, myoclonus, infrequent
      epileptic seizure and non-progressive course without cerebellar ataxia and
      dementia. We previously reported evidence for linkage of BAFME to the region
      between D8S1784 and D8S1694 on chromosome 8q. Subsequently, other research groups
      reported mapping of the same clinical syndrome to different chromosomal loci, 2p
      and 5p, in Italian (FAME2/FCMTE2) and French (FAME3/FCMTE3) families,
      respectively. In this study, we performed a genome-wide linkage analysis using
      10K single-nucleotide polymorphism arrays and additional microsatellite markers
      to reconfirm the BAFME-linked region. The BAFME-linked region was mapped to 7.16
      Mb spanned by rs1898287 and rs2891799 on chromosomes 8q23.3-8q24.13 with a
      maximum two-point logarithm of odds score of 6.0 for the marker rs1021897.
      Sequence analysis and copy-number variant analysis of all 38 genes localized in
      the candidate region were performed, but no pathogenic mutation was identified.
      We conclude that the etiology of BAFME remains to be solved, and further genetic
      studies, which may require analysis in non-coding regions of a gene, introns or
      intergenic spacer regions, are necessary to reveal its unknown mutations.

PMID- 21850008
TI  - Mutations in mitochondrially encoded complex I enzyme as the second common cause
      in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy,
      lactic acidosis and stroke-like episodes.
AB  - The mutation pattern of mitochondrial DNA (mtDNA) in mainland Chinese patients
      with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes (MELAS) has been rarely reported, though previous data suggested that
      the mutation pattern of MELAS could be different among geographically localized
      populations. We presented the results of comprehensive mtDNA mutation analysis in
      92 unrelated Chinese patients with MELAS (85 with classic MELAS and 7 with
      MELAS/Leigh syndrome (LS) overlap syndrome). The mtDNA A3243G mutation was the
      most common causal genotype in this patient group (79/92 and 85.9%). The second
      common gene mutation was G13513A (7/92 and 7.6%). Additionally, we identified
      T10191C (p.S45P) in ND3, A11470C (p. K237N) in ND4, T13046C (p.M237T) in ND5 and
      a large-scale deletion (13025-13033:14417-14425) involving partial ND5 and ND6
      subunits of complex I in one patient each. Among them, A11470C, T13046C and the
      single deletion were novel mutations. In summary, patients with mutations
      affecting mitochondrially encoded complex I (MTND) reached 12.0% (11/92) in this
      group. It is noteworthy that all seven patients with MELAS/LS overlap syndrome
      were associated with MTND mutations. Our data emphasize the important role of
      MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap
      syndrome.

PMID- 21850009
TI  - HRAS mutants identified in Costello syndrome patients can induce cellular
      senescence: possible implications for the pathogenesis of Costello syndrome.
AB  - Costello syndrome (CS) is a congenital disease that is characterized by a
      distinctive facial appearance, failure to thrive, mental retardation and
      cardiomyopathy. In 2005, we discovered that heterozygous germline mutations in
      HRAS caused CS. Several studies have shown that CS-associated HRAS mutations are
      clustered in codons 12 and 13, and mutations in other codons have also been
      identified. However, a comprehensive comparison of the substitutions identified
      in patients with CS has not been conducted. In the current study, we identified
      four mutations (p.G12S, p.G12A, p.G12C and p.G12D) in 21 patients and analyzed
      the associated clinical manifestations of CS in these individuals. To examine
      functional differences among the identified mutations, we characterized a total
      of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13,
      p.K117R and p.A146T. The p.A146T mutant demonstrated the weakest Raf-binding
      activity, and the p.K117R and p.A146T mutants had weaker effects on downstream c
      Jun N-terminal kinase signaling than did codon 12 or 13 mutants. We demonstrated
      that these mutant HRAS proteins induced senescence when overexpressed in human
      fibroblasts. Oncogene-induced senescence is a cellular reaction that controls
      cell proliferation in response to oncogenic mutation and it has been considered
      one of the tumor suppression mechanisms in vivo. Our findings suggest that the
      HRAS mutations identified in CS are sufficient to cause oncogene-induced
      senescence and that cellular senescence might therefore contribute to the
      pathogenesis of CS.

PMID- 21850011
TI  - Waist circumference and hypertension: also applicable in diabetic patients?

PMID- 21850014
TI  - Technique of traction-free nerve-sparing robotic prostatectomy: delicate tissue
      handling by real-time penile oxygen monitoring.
AB  - It is postulated that intraoperative injury to the cavernosal nerves results in
      hemodynamic and histologic changes within the penis, which manifest clinically as
      ED. We hypothesize that non-neuronal cause, such as vascular insults due to
      intraoperative tissue handling, may also have a minor but definite role in penile
      ischemia and consequent postoperative sexual dysfunction. Between May 2008 and
      July 2008, 64 patients were enrolled in the study (group 1). Following
      sterilization, the Odissey Tissue Oximeter probe was placed on the shaft of the
      penis, 2 cm from its base. The patient underwent continuous penile tissue
      saturation monitoring. Surgical dissection was altered whenever the oxygen
      saturation alarm went off until it was restored to ?85%. In addition, 192
      patients, matched for age, preoperative prostate-specific antigen, clinical
      stage, baseline sexual function, Charlson comorbidity index and nerve-sparing
      status operated between October 2007 and July 2008, formed the control group
      (group 2). These patients did not have any intraoperative tissue oxygenation
      monitoring. Opening of the endopelvic fascia and steps of nerve sparing were
      associated with significant drops in oxygen levels, especially if done using
      torque. Drop in oxygen levels were also noted whenever excessive traction was
      applied on the Foley catheter, seminal vesicles or prostate during apical
      dissection. We deliberately modified our surgical steps to make surgery more
      traction free. A significantly higher percentage of group 1 patients with
      bilateral nerve sparing had no ED compared with group 2 patients at 6 weeks
      (24.5% vs 10.4%; P=0.014) and 52 weeks (83.7% vs 68%; P=0.029). Overall, 93.9% of
      patients in study group had Sexual Health Inventory for Men (SHIM) score of ?17
      (mild to no ED) at 1 year compared with 78.4% of patients in the control group.
      We demonstrated that avoidance of ischemic stress, aided by intraoperative penile
      oxygenation monitoring, may help surgeons improve their technique and thus
      functional outcomes in patients.

PMID- 21850017
TI  - Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte
      reactivity against TLR9 ligands.
AB  - Here we show that keratinocytes in psoriatic lesional skin express increased Toll
      like receptor (TLR) 9 that similarly localizes with elevated expression of the
      cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes
      exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were
      exposed to LL-37 and subsequently treated with TLR9 ligands, such as CpG or
      genomic DNA, they greatly increased production of type I IFNs. This response
      mimicked observations in the epidermis of psoriatic lesional skin as
      keratinocytes in psoriatic lesions produce greater amounts of IFN-beta than
      normal skin lacking LL-37. The mechanism for induction of type I IFNs in
      keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex.
      These findings suggest that keratinocytes recognize and respond to DNA and can
      actively participate in contributing to the immunological environment that
      characterizes psoriasis.

PMID- 21850018
TI  - SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen
      I/alpha2beta1 integrin axis.
AB  - In melanoma, the extracellular protein SPARC (secreted protein acidic and rich in
      cysteine) is related to tumor progression. Some of the evidence that links SPARC
      to melanoma progression indicates that SPARC may be involved in the acquisition
      of mesenchymal traits that favor metastatic dissemination. However, no molecular
      pathways that link extracellular SPARC to a mesenchymal phenotype have been
      described. In this study, global protein expression analysis of the melanoma
      secretome following enforced downregulation of SPARC expression led us to
      elucidate a new molecular mechanism by which SPARC promotes cathepsin B-mediated
      melanoma invasiveness using collagen I and alpha2beta1 integrins as mediators.
      Interestingly, we also found that the transforming growth factor (TGF)-beta1
      contribution to cathepsin B-mediated invasion is highly SPARC dependent. In
      addition, induction of the E-cadherin to N-cadherin switch by SPARC enabled
      melanoma cells to transmigrate across an endothelial layer through a mechanism
      independent to that of enhancing invasion. Finally, SPARC also enhanced the
      extracellular expression of other proteins involved in epithelial-mesenchymal
      transformation, such as family with sequence similarity 3, member C/interleukin
      like EMT-inducer. Our findings demonstrate a previously unreported molecular
      pathway for SPARC activity on invasion and support an active role of SPARC in the
      mesenchymal transformation that contributes to melanoma dissemination.

PMID- 21850019
TI  - Immunomodulation by imiquimod in patients with high-risk primary melanoma.
AB  - Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the
      topical treatment of actinic keratoses, superficial basal cell carcinoma, and
      genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna;
      however, studies of invasive melanoma are lacking. We conducted a pilot study to
      characterize the local, regional, and systemic immune responses induced by
      imiquimod in patients with high-risk melanoma. After treatment of the primary
      melanoma biopsy site with placebo or imiquimod cream, we measured immune
      responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood.
      Treatment of primary melanomas with 5% imiquimod cream was associated with an
      increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN.
      Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any
      increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted
      melanoma epitopes in the peripheral blood. The findings from this small pilot
      study demonstrate that topical imiquimod treatment results in enhanced local and
      regional T-cell numbers in both the skin and SLN. Further research into TLR7
      immunomodulating pathways as a basis for effective immunotherapy against melanoma
      in conjunction with surgery is warranted.

PMID- 21850021
TI  - Transcriptomic analysis of mouse embryonic skin cells reveals previously
      unreported genes expressed in melanoblasts.
AB  - Studying the development of melanoblasts, precursors of melanocytes, is
      challenging owing to their scarcity and dispersion in the skin embryo. However,
      this is an important subject because diverse diseases are associated with
      defective melanoblast development. Consequently, characterizing patterns of
      expression in melanoblasts during normal development is an important issue. This
      requires isolating enough melanoblasts during embryonic development to obtain
      sufficient RNA to study their transcriptome. ZEG reporter mouse line crossed with
      Tyr::Cre mouse line was used to label melanoblasts by enhanced green fluorescent
      protein (EGFP) autofluorescence. We isolated melanoblasts by FACS from the skin
      of E14.5-E16.5 embryos, and obtained sufficient cells for large-scale
      transcriptomic analysis after RNA isolation and amplification. We confirmed our
      array-based data for various genes of interest by standard quantitative real-time
      RT-PCR. We demonstrated that phosphatase and tensin homolog was expressed in
      melanoblasts but BRN2 was not, although both are involved in melanomagenesis. We
      also revealed the potential contribution of genes not previously implicated in
      any function in melanocytes or even in neural crest derivatives. Finally, the
      Schwann cell markers, PLP1 and FABP7, were significantly expressed in
      melanoblasts, melanocytes, and melanoma. This study demonstrates the feasibility
      of the transcriptomic analysis of purified melanoblasts at different embryonic
      stages and reveals the involvement of previously unreported genes in melanoblast
      development.

PMID- 21850020
TI  - Enhanced inflammation and accelerated wound closure following tetraphorbol ester
      application or full-thickness wounding in mice lacking hyaluronan synthases Has1
      and Has3.
AB  - Hyaluronan (HA) is an abundant matrix molecule, the function of which in the skin
      remains to be fully defined. To explore the roles of HA in cutaneous injury
      responses, double-knockout mice (abbreviated as Has1/3 null) that lack two HA
      synthase enzymes (Has1 and Has3), but still express functional Has2, were used in
      two types of experiments: (i) application of 12-O-tetradecanoylphorbol-13-acetate
      (TPA) and (ii) full-thickness wounding of the skin. Uninjured Has1/3-null mice
      were phenotypically normal. However, after TPA, the accumulation of HA that
      normally occurs in wild-type epidermis was blunted in Has1/3-null epidermis. In
      excisional wound-healing experiments, wound closure was significantly faster in
      Has1/3 null than in wild-type mice. Coincident with this abnormal wound healing,
      a marked decrease in epidermal and dermal HA and a marked increase in neutrophil
      efflux from cutaneous blood vessels were observed in Has1/3-null skin relative to
      wild-type skin. Has1/3-null wounds displayed an earlier onset of myofibroblast
      differentiation. In summary, selective loss of Has1 and Has3 leads to a
      proinflammatory milieu that favors recruitment of neutrophils and other
      inflammation-related changes in the dermis.

PMID- 21850022
TI  - Transcriptional profiling of psoriasis using RNA-seq reveals previously
      unidentified differentially expressed genes.

PMID- 21850023
TI  - Incidence, mortality, and causes of death of patients with pemphigus in Taiwan: a
      nationwide population-based study.
AB  - Pemphigus is a potentially life-threatening autoimmune blistering disease.
      However, little is known about the all-cause and cause-specific mortality among
      patients with pemphigus compared with the general population. The incidence of
      pemphigus in Taiwan has not been described previously. The objective of this
      study was to estimate the incidence of pemphigus in Taiwan and to investigate the
      overall mortality, causes of death, and cause-specific mortality in a nationwide
      population-based cohort of pemphigus patients. The study cohort included 853
      patients newly diagnosed with pemphigus between 2002 and 2009 in the National
      Health Insurance Research Database. Survival status, date of death, and cause of
      death were ascertained by linking the study cohort with the National Register of
      Deaths Database of Taiwan. All-cause and cause-specific standardized mortality
      ratios (SMRs) were estimated. The incidence of pemphigus in Taiwan was 4.7 (95%
      confidence interval (CI), 3.2-6.2) per million per year. Overall, 88 deaths were
      observed during a mean follow-up period of 3.8 years, which was more than two
      times the number expected (SMR, 2.36; 95% confidence interval, 1.92-2.91). In the
      analysis of causes of death, the SMRs for death due to pneumonia (3.64; 95% CI,
      1.30-10.21), septicemia (11.57; 95% CI, 2.95-45.34), cardiovascular disease
      (2.69; 95% CI, 1.18-6.12), and peptic ulcer disease (8.44; 95% CI, 1.22-58.21)
      were significantly higher than expected. We concluded that the incidence of
      pemphigus is not low in Taiwan, and the overall mortality among pemphigus
      patients is two times greater than that of the general population. In particular,
      patients with pemphigus have higher risk of mortality from systemic and
      respiratory tract infections, cardiovascular disease, and peptic ulcer disease.

PMID- 21850024
TI  - Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation
      is safe and decreases acute graft-versus-host disease.
AB  - Depletion of host Langerhans cells (LCs) prevents cutaneous graft-versus-host
      disease (GvHD) in mice. We analyzed whether UVB irradiation is tolerated during
      the course of human allogeneic hematopoietic cell transplantation and whether
      depletion of LCs by broadband UVB could improve GvHD outcome. A total of 17
      patients received six whole-body UVB irradiations with 75% of the individually
      determined minimal erythemal dose after conditioning with a reduced intensity
      protocol. LCs, dermal dendritic cells (DCs), and macrophages were analyzed before
      and after UVB irradiation by immunohistochemical analysis. Circulating blood
      cells and serum factors were analyzed in parallel. In striking contrast to
      previous data, our irradiation protocol was well tolerated in all patients. UVB
      treatment decreased the number of LCs and also affected dermal DCs. UVB-treated
      patients also had significantly higher 25-hydroxyvitamin D3 serum levels and
      higher numbers of circulating CD4+ FoxP3+ regulatory T cells. Strikingly, nine
      out of nine patients with complete LC depletion (<1 LC per field) developed only
      grade I GvHD or no GvHD up to day 100. Our results strongly suggest that
      prophylactic UVB irradiation post transplant is safe and should be further
      explored as a clinical strategy to prevent acute (skin) GvHD.

PMID- 21850026
TI  - Sphere formation increases the ability of cultured human dermal papilla cells to
      induce hair follicles from mouse epidermal cells in a reconstitution assay.

PMID- 21850025
TI  - Autocrine regulation of re-epithelialization after wounding by chemokine
      receptors CCR1, CCR10, CXCR1, CXCR2, and CXCR3.
AB  - This study identifies chemokine receptors involved in an autocrine regulation of
      re-epithelialization after skin tissue damage. We determined which receptors,
      from a panel of 13, are expressed in healthy human epidermis and which
      monospecific chemokine ligands, secreted by keratinocytes, were able to stimulate
      migration and proliferation. A reconstructed epidermis cryo(freeze)-wound model
      was used to assess chemokine secretion after wounding and the effect of pertussis
      toxin (chemokine receptor blocker) on re-epithelialization and differentiation.
      Chemokine receptors CCR1, CCR3, CCR4, CCR6, CCR10, CXCR1, CXCR2, CXCR3, and CXCR4
      were expressed in epidermis. No expression of CCR2, CCR5, CCR7, and CCR8 was
      observed by either immunostaining or flow cytometry. Five chemokine receptors
      (CCR1, CCR10, CXCR1, CXCR2, and CXCR3) were identified, the corresponding
      monospecific ligands (CCL14, CCL27, CXCL8, CXCL1, CXCL10, respectively) of which
      were not only able to stimulate keratinocyte migration and/or proliferation but
      were also secreted by keratinocytes after introducing cryo-wounds into epidermal
      equivalents. Blocking of receptor-ligand interactions with pertussis toxin
      delayed re-epithelialization, but did not influence differentiation (as assessed
      by formation of basal layer, spinous layer, granular layer, and stratum corneum)
      after cryo-wounding. Taken together, these results confirm that an autocrine
      positive-feedback loop of epithelialization exists in order to stimulate wound
      closure after skin injury.

PMID- 21850027
TI  - Expression of the anti-apoptotic protein BAG3 in human melanomas.

PMID- 21850029
TI  - Merkel cell carcinoma and Merkel cell polyomavirus: evidence for hit-and-run
      oncogenesis.

PMID- 21850028
TI  - Plasmacytoid dendritic cells infiltrate the skin in positive tuberculin skin test
      indurations.
AB  - Plasmacytoid dendritic cells (pDCs) are rarely present in normal skin but have
      been shown to infiltrate lesions of infections or autoimmune disorders. Here, we
      report that several DC subsets including CD123(+) BDCA-2/CD303(+) pDCs accumulate
      in the dermis in indurations induced by the tuberculin skin test (TST), used to
      screen immune sensitization by Mycobacterium tuberculosis. Although the purified
      protein derivate (PPD) used in the TST did not itself induce pDC recruitment or
      IFN-alpha production, the positive skin reactions showed high expression of the
      IFN-alpha-inducible protein MxA. In contrast, the local immune response to PPD
      was associated with substantial cell death and high expression of the cationic
      antimicrobial peptide LL37, which together can provide a means for pDC activation
      and IFN-alpha production. In vitro, pDCs showed low uptake of PPD compared with
      CD11c(+) and BDCA-3/CD141(+) myeloid DC subsets. Furthermore, supernatants from
      pDCs activated with LL37-DNA complexes reduced the high PPD uptake in myeloid
      DCs, as well as decreased their capacity to activate T-cell proliferation.
      Infiltrating pDCs in the TST reaction site may thus have a regulatory effect upon
      the antigen processing and presentation functions of surrounding potent myeloid
      DC subsets to limit potentially detrimental and excessive immune stimulation.

PMID- 21850030
TI  - Rare mutations in TNFRSF13B increase the risk of asthma symptoms in Swedish
      children.
AB  - TACI (transmembrane activator and calcium modulator and cyclophilin ligand
      interactor) mutations seem to be associated with autoimmunity and common variable
      immunodeficiency in humans. Because of its role in immune responses, we
      investigated the association between TACI mutations and infection
      proneness/asthma symptoms in children. A total of 2372 children were genotyped
      for TACI mutations (I87N, C104R, S144X, A181E, R202H and ins204A). Serum IgA, IgG
      and specific IgE levels were determined in children with mutations. Data on
      parentally reported allergic diseases and infections were collected. In all, 55
      individuals with TACI mutations were identified. Children with TACI mutations had
      a 2-fold increased risk of wheeze at 2 and 4 years of age and a 2.5-fold
      increased risk of asthma was seen at 4 years of age. None of the children with
      mutations suffered from IgA deficiency (<0.07 g l(-1)). No significant
      differences in serum IgG levels or specific IgE were found. Common variants in
      asthma susceptibility genes may account for up to 40% of cases of childhood-onset
      asthma, indicating a high contribution, compared with other common disorders. The
      role of rare variants/mutations in the pathogenesis of asthma is less clear. We
      conclude that mutations in TACI are the contributing factors for asthma symptoms
      in Swedish children, although the mechanisms still remain elusive.

PMID- 21850031
TI  - Evidence for two independent associations with type 1 diabetes at the 12q13
      locus.
AB  - Genome-wide association studies have identified associations between type 1
      diabetes and single-nucleotide polymorphisms (SNPs) at chromosome 12q13,
      surrounding the gene ERBB3. Our objective was to fine map this region to further
      localize causative variants. Re-sequencing identified more than 100 putative SNPs
      in an 80-kb region at 12q13. By genotyping 42 SNPs, spanning ~214 kb, in 382
      affected sibling pair type 1 diabetes families, we were able to genotype or tag
      67 common SNPs (MAF>=0.05) identified from HapMap CEU data and CEU data from the
      1000 Genomes Project, plus additional rare coding variants identified from our re
      sequencing efforts. In all, 15 SNPs provided nominal evidence for association
      (P<=0.05), with type 1 diabetes. The most significant associations were observed
      with rs2271189 (P=4.22 * 10(-5)), located in exon 27 of the ERBB3 gene, and an
      intergenic SNP rs11171747 (P=1.70 * 10(-4)). Follow-up genotyping of these SNPs
      in 2740 multiplex type 1 diabetes families validated these findings. After
      analyzing variants spanning more than 200 kb, we have replicated associations
      from previous GWAS and provide evidence for novel associations with type 1
      diabetes. The associations across this region could be entirely accounted for by
      two common SNPs, rs2271189 and rs11171747.

PMID- 21850032
TI  - Staying big-brained.

PMID- 21850033
TI  - A new platform for death.

PMID- 21850034
TI  - Checkpoint tension relief.

PMID- 21850035
TI  - Understanding morphogenetic growth control -- lessons from flies.
AB  - Morphogens are secreted signalling molecules that control the patterning and
      growth of developing organs. How morphogens regulate patterning is fairly well
      understood; however, how they control growth is less clear. Four principal models
      have been proposed to explain how the morphogenetic protein Decapentaplegic (DPP)
      controls the growth of the wing imaginal disc in the fly. Recent studies in this
      model system have provided a wealth of experimental data on growth and DPP
      gradient properties, as well as on the interactions of DPP with other signalling
      pathways. These findings have allowed a more precise formulation and evaluation
      of morphogenetic growth models. The insights into growth control by the DPP
      gradient will also be useful for understanding other morphogenetic growth
      systems.

PMID- 21850036
TI  - O-GlcNAc signalling: implications for cancer cell biology.
AB  - O-GlcNAcylation is the covalent attachment of beta-D-N-acetylglucosamine (GlcNAc)
      sugars to serine or threonine residues of nuclear and cytoplasmic proteins, and
      it is involved in extensive crosstalk with other post-translational
      modifications, such as phosphorylation. O-GlcNAcylation is becoming increasing
      realized as having important roles in cancer-relevant processes, such as cell
      signalling, transcription, cell division, metabolism and cytoskeletal regulation.
      However, currently little is known about the specific roles of aberrant O
      GlcNAcylation in cancer. In this Opinion article, we summarize the current
      understanding of O-GlcNAcylation in cancer and its emerging functions in
      transcriptional regulation at the level of chromatin and transcription factors.

PMID- 21850040
TI  - Human disease: a short story of breast cancer risk.

PMID- 21850037
TI  - What does physics have to do with cancer?
AB  - Large-scale cancer genomics, proteomics and RNA-sequencing efforts are currently
      mapping in fine detail the genetic and biochemical alterations that occur in
      cancer. However, it is becoming clear that it is difficult to integrate and
      interpret these data and to translate them into treatments. This difficulty is
      compounded by the recognition that cancer cells evolve, and that initiation,
      progression and metastasis are influenced by a wide variety of factors. To help
      tackle this challenge, the US National Cancer Institute Physical Sciences
      Oncology Centers initiative is bringing together physicists, cancer biologists,
      chemists, mathematicians and engineers. How are we beginning to address cancer
      from the perspective of the physical sciences?

PMID- 21850041
TI  - Learning about human population history from ancient and modern genomes.
AB  - Genome-wide data, both from SNP arrays and from complete genome sequencing, are
      becoming increasingly abundant and are now even available from extinct hominins.
      These data are providing new insights into population history; in particular,
      when combined with model-based analytical approaches, genome-wide data allow
      direct testing of hypotheses about population history. For example, genome-wide
      data from both contemporary populations and extinct hominins strongly support a
      single dispersal of modern humans from Africa, followed by two archaic admixture
      events: one with Neanderthals somewhere outside Africa and a second with
      Denisovans that (so far) has only been detected in New Guinea. These new
      developments promise to reveal new stories about human population history,
      without having to resort to storytelling.

PMID- 21850043
TI  - Needles in stacks of needles: finding disease-causal variants in a wealth of
      genomic data.
AB  - Genome and exome sequencing yield extensive catalogues of human genetic
      variation. However, pinpointing the few phenotypically causal variants among the
      many variants present in human genomes remains a major challenge, particularly
      for rare and complex traits wherein genetic information alone is often
      insufficient. Here, we review approaches to estimate the deleteriousness of
      single nucleotide variants (SNVs), which can be used to prioritize disease-causal
      variants. We describe recent advances in comparative and functional genomics that
      enable systematic annotation of both coding and non-coding variants. Application
      and optimization of these methods will be essential to find the genetic answers
      that sequencing promises to hide in plain sight.

PMID- 21850042
TI  - Dynamic interactions between transposable elements and their hosts.
AB  - Transposable elements (TEs) have a unique ability to mobilize to new genomic
      locations, and the major advance of second-generation DNA sequencing has provided
      insights into the dynamic relationship between TEs and their hosts. It now is
      clear that TEs have adopted diverse strategies - such as specific integration
      sites or patterns of activity - to thrive in host environments that are replete
      with mechanisms, such as small RNAs or epigenetic marks, that combat TE
      amplification. Emerging evidence suggests that TE mobilization might sometimes
      benefit host genomes by enhancing genetic diversity, although TEs are also
      implicated in diseases such as cancer. Here, we discuss recent findings about
      how, where and when TEs insert in diverse organisms.

PMID- 21850044
TI  - Understanding the transcriptome through RNA structure.
AB  - RNA structure is crucial for gene regulation and function. In the past,
      transcriptomes have largely been parsed by primary sequences and expression
      levels, but it is now becoming feasible to annotate and compare transcriptomes
      based on RNA structure. In addition to computational prediction methods, the
      recent advent of experimental techniques to probe RNA structure by high
      throughput sequencing has enabled genome-wide measurements of RNA structure and
      has provided the first picture of the structural organization of a eukaryotic
      transcriptome - the 'RNA structurome'. With additional advances in method
      refinement and interpretation, structural views of the transcriptome should help
      to identify and validate regulatory RNA motifs that are involved in diverse
      cellular processes and thereby increase understanding of RNA function.

PMID- 21850045
TI  - Advances in prenatal screening: the ethical dimension.
AB  - Prenatal screening strategies are undergoing rapid changes owing to the
      introduction of new testing techniques. The overall tendency is towards
      broadening the scope of prenatal testing through increasingly sensitive
      ultrasound scans and genome-wide molecular tests. In addition, non-invasive
      prenatal diagnosis is likely to be introduced in the near future. These
      developments raise important ethical questions concerning meaningful reproductive
      choice, the autonomy rights of future children, equity of access and the
      proportionality of testing.

PMID- 21850046
TI  - Adaptation due to symbionts and conflicts between heritable agents of biological
      information.

PMID- 21850049
TI  - Commenting on communicator RNA.

PMID- 21850048
TI  - TNFR1 and TNFR2 regulate the extrinsic apoptotic pathway in myeloma cells by
      multiple mechanisms.
AB  - The huge majority of myeloma cell lines express TNFR2 while a substantial subset
      of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1
      expressing subset of MM cell lines had no or only a very mild effect on cellular
      viability. Surprisingly, however, TNF stimulation enhanced cell death induction
      by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation
      of TRAIL- and CD95L-induced cell death by TNF could be traced back to the
      concomitant NFkappaB-mediated upregulation of CD95 and the antiapoptotic FLIP
      protein. It appeared that CD95 induction, due to its strength, overcompensated a
      rather moderate upregulation of FLIP so that the net effect of TNF-induced
      NFkappaB activation in the context of CD95 signaling is pro-apoptotic. TRAIL
      induced cell death, however, was antagonized in response to TNF because in this
      context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma
      cells leads to TRAF2 depletion. In line with this, we observed cell death
      induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the
      TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic
      pathway in myeloma cells by multiple mechanisms that generate a highly context
      dependent net effect on myeloma cell survival.

PMID- 21850047
TI  - Novel roles for hERG K(+) channels in cell proliferation and apoptosis.
AB  - The human ether-a-go-go-related gene potassium channel (hERG, Kv11.1, KCNH2) has
      an essential role in cardiac action potential repolarization. Electrical
      dysfunction of the voltage-sensitive ion channel is associated with potentially
      lethal ventricular arrhythmias in humans. hERG K(+) channels are also expressed
      in a variety of cancer cells where they control cell proliferation and apoptosis.
      In this review, we discuss molecular mechanisms of hERG-associated cell cycle
      regulation and cell death. In addition, the significance of hERG K(+) channels as
      future drug target in anticancer therapy is highlighted.

PMID- 21850050
TI  - Epidermal growth factor improves lentivirus vector gene transfer into primary
      mouse hepatocytes.
AB  - Partial resistance of primary mouse hepatocytes to lentiviral (LV) vector
      transduction poses a challenge for ex vivo gene therapy protocols in models of
      monogenetic liver disease. We thus sought to optimize ex vivo LV gene transfer
      while preserving the hepatocyte integrity for subsequent transplantation into
      recipient animals. We found that culture media supplemented with epidermal growth
      factor (EGF) and, to a lesser extent, hepatocyte growth factor (HGF) markedly
      improved transduction efficacy at various multiplicities of infection. Up to 87%
      of primary hepatocytes were transduced in the presence of 10 ng EGF, compared
      with ~30% in standard culture medium (SCMs). The increased number of transgene
      expressing cells correlated with increased nuclear import and more integrated pro
      viral copies per cell. Higher LV transduction efficacy was not associated with
      proliferation, as transduction capacity of gammaretroviral vectors remained low
      (<1%). Finally, we developed an LV transduction protocol for short-term (maximum
      24 h) adherent hepatocyte cultures. LV-transduced hepatocytes showed liver
      repopulation capacities similar to freshly isolated hepatocytes in alb-uPA mouse
      recipients. Our findings highlight the importance of EGF for efficient LV
      transduction of primary hepatocytes in culture and should facilitate studies of
      LV gene transfer in mouse models of monogenetic liver disease.

PMID- 21850051
TI  - AAV vectors transduce hepatocytes in vivo as efficiently in cirrhotic as in
      healthy rat livers.
AB  - In liver cirrhosis, abnormal liver architecture impairs efficient transduction of
      hepatocytes with large viral vectors such as adenoviruses. Here we evaluated the
      ability of adeno-associated virus (AAV) vectors, small viral vectors, to
      transduce normal and cirrhotic rat livers. Using AAV serotype-1 (AAV1) encoding
      luciferase (AAV1Luc) we analyzed luciferase expression with a CCD camera. AAV1Luc
      was injected through the hepatic artery (intra-arterial (IA)), the portal vein
      (intra-portal (IP)), directly into the liver (intra-hepatic (IH)) or infused into
      the biliary tree (intra-biliar). We found that AAV1Luc allows long-term and
      constant luciferase expression in rat livers. Interestingly, IP administration
      leads to higher expression levels in healthy than in cirrhotic livers, whereas
      the opposite occurs when using IA injection. IH administration leads to similar
      transgene expression in cirrhotic and healthy rats, whereas intra-biliar infusion
      is the least effective route. After 70% partial hepatectomy, luciferase
      expression decreased in the regenerating liver, suggesting lack of efficient
      integration of AAV1 DNA into the host genome. AAV1Luc transduced mainly the liver
      but also the testes and spleen. Within the liver, transgene expression was found
      mainly in hepatocytes. Using a liver-specific promoter, transgene expression was
      detected in hepatocytes but not in other organs. Our results indicate that AAVs
      are convenient vectors for the treatment of liver cirrhosis.

PMID- 21850052
TI  - Sustained correction of OTC deficiency in spf( ash) mice using optimized self
      complementary AAV2/8 vectors.
AB  - Ornithine transcarbamylase deficiency (OTCD) is the most common inborn error of
      urea synthesis. Complete OTCD can result in hyperammonemic coma in the neonatal
      period, which can rapidly become fatal. Current acute therapy involves dialysis;
      chronic therapy involves the stimulation of alternate nitrogen clearance
      pathways; and the only curative approach is liver transplantation. Adeno
      associated virus (AAV) vector-based gene therapy would add to current treatment
      options provided the vector delivers high level and stable transgene expression
      in liver without dose-limiting toxicity. In this study, we employed an AAV2/8
      based self-complementary (sc) vector expressing the murine OTC (mOTC) gene under
      a liver-specific thyroxine-binding globulin promoter and examined the therapeutic
      effects in a mouse model of OTCD, the spf (ash) mouse. Seven days after a single
      intravenous injection of vector, treated mice showed complete normalization of
      urinary orotic acid, a measure of OTC activity. We further improved vector
      efficacy by incorporating a Kozak or Kozak-like sequence into mOTC complementary
      DNA, which increased the OTC activity by five or twofold and achieved sustained
      correction of orotic aciduria for up to 7 months. Our results demonstrate that
      vector optimizations can significantly improve the efficacy of gene therapy.

PMID- 21850053
TI  - HPV-16 E1, E2 and E6 each complement the Ad5 helper gene set, increasing rAAV2
      and wt AAV2 production.
AB  - Adeno-associated virus type 2 (AAV) is a popular vector for human gene therapy,
      because of its safety record and ability to express genes long term. Yet large
      scale recombinant (r) AAV production remains problematic because of low particle
      yield. The adenovirus (Ad) and herpes (simplex) virus helper genes for AAV have
      been widely used and studied, but the helper genes of human papillomavirus (HPV)
      have not. HPV-16 E1, E2 and E6 help wild-type (wt) AAV productive infection in
      differentiating keratinocytes, however, HEK293 cells are the standard cell line
      used for generating rAAV. Here we demonstrate that the three HPV genes were
      unable to stimulate significant rAAV replication in HEK293 cells when used alone.
      However, when used in conjunction (complementation) with the standard Ad5 helper
      gene set, E1, E2 and E6 were each capable of significantly boosting rAAV DNA
      replication and virus particle yield. Moreover, wt AAV DNA replication and virion
      yield were also significantly boosted by each HPV gene along with wt Ad5 virus co
      infection. Mild-to-moderate changes in rep- and cap-encoded protein levels were
      evident in the presence of the E1, E2 and E6 genes. Higher wt AAV DNA replication
      was not matched by similar increases in the levels of rep-encoded protein.
      Moreover, although rep mRNA was upregulated, cap mRNA was upregulated more.
      Higher virus yields did correlate most consistently with increased Rep52-, VP3-
      and VP-related 21/31 kDa species. The observed boost in wt and rAAV production by
      HPV genes was not unexpected, as the Ad and HPV helper gene sets do not seem to
      recapitulate each other. These results raise the possibility of generating
      improved helper gene sets derived from both the Ad and HPV helper gene sets.

PMID- 21850054
TI  - Health worker shortages in Zambia: an assessment of government responses.
AB  - A dire health worker shortage in Zambia's national health programs is adversely
      impacting the quantity and quality of health care and posing a serious barrier to
      achieving Millennium Development Goals to improve population health. In 2005,
      Zambia's Ministry of Health developed a 10-year strategic plan for human
      resources for health to address the crisis through improved training, hiring, and
      retention. The plan has neither arrested nor reduced the shortage. We review the
      causes of the shortage, present results from a health worker survey showing that
      safe work conditions, manageable workloads, and career advancement opportunities
      matter more to respondents than financial compensation. We comment on the
      adequacy of government efforts to address the health worker shortage.

PMID- 21850055
TI  - Defining seasonal marine microbial community dynamics.
AB  - Here we describe, the longest microbial time-series analyzed to date using high
      resolution 16S rRNA tag pyrosequencing of samples taken monthly over 6 years at a
      temperate marine coastal site off Plymouth, UK. Data treatment effected the
      estimation of community richness over a 6-year period, whereby 8794 operational
      taxonomic units (OTUs) were identified using single-linkage preclustering and 21
      130 OTUs were identified by denoising the data. The Alphaproteobacteria were the
      most abundant Class, and the most frequently recorded OTUs were members of the
      Rickettsiales (SAR 11) and Rhodobacteriales. This near-surface ocean bacterial
      community showed strong repeatable seasonal patterns, which were defined by
      winter peaks in diversity across all years. Environmental variables explained far
      more variation in seasonally predictable bacteria than did data on protists or
      metazoan biomass. Change in day length alone explains >65% of the variance in
      community diversity. The results suggested that seasonal changes in environmental
      variables are more important than trophic interactions. Interestingly, microbial
      association network analysis showed that correlations in abundance were stronger
      within bacterial taxa rather than between bacteria and eukaryotes, or between
      bacteria and environmental variables.

PMID- 21850056
TI  - Structural segregation of gut microbiota between colorectal cancer patients and
      healthy volunteers.
AB  - Despite a long-suspected role in the development of human colorectal cancer
      (CRC), the composition of gut microbiota in CRC patients has not been adequately
      described. In this study, fecal bacterial diversity in CRC patients (n=46) and
      healthy volunteers (n=56) were profiled by 454 pyrosequencing of the V3 region of
      the 16S ribosomal RNA gene. Both principal component analysis and UniFrac
      analysis showed structural segregation between the two populations. Forty-eight
      operational taxonomic units (OTUs) were identified by redundancy analysis as key
      variables significantly associated with the structural difference. One OTU
      closely related to Bacteroides fragilis was enriched in the gut microbiota of CRC
      patients, whereas three OTUs related to Bacteroides vulgatus and Bacteroides
      uniformis were enriched in that of healthy volunteers. A total of 11 OTUs
      belonging to the genera Enterococcus, Escherichia/Shigella, Klebsiella,
      Streptococcus and Peptostreptococcus were significantly more abundant in the gut
      microbiota of CRC patients, and 5 OTUs belonging to the genus Roseburia and other
      butyrate-producing bacteria of the family Lachnospiraceae were less abundant.
      Real-time quantitative PCR further validated the significant reduction of
      butyrate-producing bacteria in the gut microbiota of CRC patients by measuring
      the copy numbers of butyryl-coenzyme A CoA transferase genes (Mann-Whitney test,
      P<0.01). Reduction of butyrate producers and increase of opportunistic pathogens
      may constitute a major structural imbalance of gut microbiota in CRC patients.

PMID- 21850057
TI  - Variants on chromosome 6p22.3 associated with blood pressure in the HyperGEN
      study: follow-up of FBPP quantitative trait loci.
AB  - BACKGROUND: A recent meta-analysis of genome-wide linkage scans of blood pressure
      (BP) in the large (N = 13,044) Family Blood Pressure Program (FBPP) identified
      five quantitative trait loci (QTLs) on chromosomes 6, 8, 20, and 21. We conducted
      follow-up fine mapping studies in 1,251 African (AA) and 1,254 European American
      (EA) participants of the Hypertension Genetic Epidemiology Network (HyperGEN).
      METHODS: Ethnic-specific linear mixed effects models were used to test
      associations of BP with genotyped and imputed single nucleotide polymorphisms
      (SNPs) contained in the logarithm of odds (LOD) score >=2 interval under each of
      the QTL peaks. We used multipoint variance components models to perform linkage
      analysis conditional on each significant SNP in the QTL region to see if the SNP
      explained the QTL. RESULTS: Three intergenic SNPs (rs898164, rs2876587,
      rs6935795) on chromosome 6p22.3 were significantly associated with pulse pressure
      (using appropriate Bonferroni correction). Conditioning on the significant SNPs
      reduced the chromosome 6 QTL linkage evidence by 14-30%. Both AAs and EAs
      exhibited suggestive associations between BP and intronic SNPs on chromosomes
      8q24.12 (genes: OPG in AAs, SAMD12 in EAs), 20q13.12 (genes: SLC13A3 in AAs,
      SLC12A5 in EAs), and 21q21.1 (genes: C21orf34 in AAs, BC039377 in EAs).
      CONCLUSIONS: Significant associations with common SNPs explained less than 1/3 of
      the QTL evidence. Our results cannot refute the hypothesis that rare variants
      account for most of the statistical evidence for the FBPP linkage peaks. Whole
      genome resequencing can identify the variants driving the linkage peaks and
      genome-wide association study (GWAS) hits thereby spurring investigations to
      deepen our understanding of hypertension pathophysiology.

PMID- 21850058
TI  - Intraprocedural cortisol measurement increases adrenal vein sampling success rate
      in primary aldosteronism.
AB  - BACKGROUND: Adrenal venous sampling (AVS) is the gold standard for the
      identification of unilateral primary aldosteronism (PA), but is technically
      difficult. The aim of our study was to assess whether intraprocedural cortisol
      measurement (IPCM) increases AVS success rate. METHODS: Twenty-five consecutive
      PA patients underwent cosyntropin-stimulated AVS. Cortisol was measured
      immediately in a first set of samples drawn from adrenal veins and inferior vena
      cava. The selectivity criterion was an adrenal vein-to-inferior vena cava
      cortisol ratio >=5. If bilateral selectivity was not achieved in a first set of
      samples, a second set was obtained during the same radiological session. PA was
      judged as unilateral if the gradient of cortisol-corrected aldosterone between
      dominant and nondominant side was >3.5. Twenty-five consecutive PA patients who
      had previously been submitted to AVS without IPCM served as historical controls.
      Lateralizing patients who underwent unilateral adrenalectomy were followed for 2
      years after surgery. RESULTS: Bilateral selectivity using IPCM was achieved in
      19/25 patients in the first set of samples, and in an additional four cases in
      the second set (92% vs. 76%; P = 0.06). The final rate of bilateral selectivity
      was higher than that obtained in the historical series (23/25 vs. 16/25, P =
      0.04), whereas bilateral selectivity in the first set of samples was not
      different from that achieved in the historical series. Nineteen lateralizing
      patients (13 of the present series, six of the historical series) were submitted
      to adrenalectomy, resulting in reversal of PA. CONCLUSIONS: IPCM increases the
      success rate of AVS.

PMID- 21850059
TI  - Blood pressure, thyroid-stimulating hormone, and thyroid disease prevalence in
      primary aldosteronism and essential hypertension.
AB  - BACKGROUND: A positive correlation between thyroid-stimulating hormone (TSH) and
      blood pressure (BP) has been identified in normotensives and in patients with
      essential hypertension (EH). This study was designed to evaluate, in primary
      aldosteronism (PA) and in EH, potential association of BP, TSH, and
      ultrasonographic changes of the thyroid. METHODS: We studied 188 patients: 92
      with PA and 96 matched essential hypertensives. Clinical and ambulatory BP (ABP),
      and thyroid function were evaluated in all patients. In PA and in a subgroup of
      EH patients (n = 65) thyroid ultrasonography was performed. RESULTS: In PA
      patients, diastolic office and diastolic ABP increased across TSH quartiles and
      multivariate analysis confirmed a positive significant correlation between TSH
      and diastolic BP, independently of aldosterone levels, body mass index (BMI),
      duration of hypertension, and age. In EH patients, we found a significant linear
      increase in systolic and diastolic ABP with increasing TSH. The prevalence of
      thyroid dysfunctions was similar in PA and EH (15% and 19%, respectively). In PA
      patients, we found a higher prevalence of ultrasonographic alterations than in EH
      (66% vs. 46%, P < 0.05). PA patients presenting morphological abnormalities had
      higher homeostasis model assessment-insulin resistance levels than patients with
      normal gland at ultrasonography (4.2 +/- 1.8 vs. 3.1 +/- 0.8 P < 0.05).
      CONCLUSIONS: We found a positive correlation between TSH and BP both in PA and EH
      patients. Moreover, in PA patients we observed a high prevalence of thyroid
      morphological alterations.

PMID- 21850060
TI  - Are retinal microvascular phenotypes associated with the 1675G/A polymorphism in
      the angiotensin II type-2 receptor gene?
AB  - BACKGROUND: The X-linked angiotensin II type-2 receptor (AT2R) gene 1675G/A
      polymorphism is located in the short intron 1 of the AT2R gene within a sequence
      motif conforming to a splice branch site. AT2R is expressed in the human retina,
      but no previous study examined the association between retinal microvascular
      phenotypes and the AT2R 1675G/A polymorphism. METHODS: In 340 subjects randomly
      selected from a Flemish population (mean age, 51.9 years; 51.5% women), we post
      processed retinal images using IVAN software to generate the retinal arteriole
      and venule equivalents (central retinal arteriolar equivalent (CRAE) and central
      retinal venular equivalent (CRVE)) and the arteriole-to-venule ratio (AVR). DNA
      fragments including the AT2R 1675G/A polymorphism were amplified by PCR. We
      applied a mixed model to assess phenotype-genotype associations while accounting
      for relatedness and covariables. RESULTS: CRAE, CRVE, and AVR averaged 151.9 um,
      215.2 um, and 0.710, respectively. CRAE was 5.5 um greater in women than men and
      decreased with age (P < 0.05). In multivariable-adjusted analyses, CRAE was
      higher in hemizygous and homozygous carriers of the AT2R A allele than in their G
      allele counterparts in both sexes combined (+4.49 um; P = 0.014) and in men
      (+4.91 um; P = 0.032) with a similar trend in women (+3.41 um; P = 0.14). AVR was
      increased in the presence of the AT2R A allele compared with AT2R G hemizygotes
      and homozygotes (+0.024; P = 0.0082). The associations of CRAE and CRVE with
      other polymorphisms were not significant. CONCLUSIONS: Pending confirmation in
      experimental and epidemiological studies, our findings suggest that diameter of
      the retinal arterioles might be associated with the AT2R 1675G/A polymorphism.

PMID- 21850062
TI  - Start small, think big.

PMID- 21850061
TI  - Quantification of the calibration error in the transfer function-derived central
      aortic blood pressures.
AB  - BACKGROUND: The accuracy of the central aortic systolic (SBP-C) and pulse (PP-C)
      blood pressures estimated noninvasively by a generalized transfer function
      technique has been questioned. The purpose of the present study was to quantify
      precisely the impact of the input errors (differences between the oscillometric
      (SBP-O, DBP-O, PP-O) and invasive (SBP-B, DBP-B, PP-B) brachial systolic,
      diastolic, and pulse blood pressures) on the output errors (differences between
      the estimated and invasively measured SBP-C and PP-C). METHODS: Invasive high
      fidelity right brachial and central aortic pressure waveforms, and SBP-O, DBP-O,
      and PP-O (=SBP-O - DBP-O) were obtained simultaneously in 40 patients during
      cardiac catheterization. A generalized transfer function was applied on the
      individual brachial pressure waveform to derive predicted SBP-C and PP-C.
      RESULTS: Observed input errors were -2.3 +/- 5.8 mm Hg from SBP-O, 8.1 +/- 5.3 mm
      Hg from DBP-O, and -10.4 +/- 7.1 mm Hg from PP-O, respectively. The output errors
      were -2.2 +/- 6.4 mm Hg and -10.3 +/- 8.0 mm Hg for SBP-C and PP-C, respectively,
      when the brachial pressure waveforms were recalibrated using SBP-O and DBP-O. The
      outputs were determined by the inputs according to the Equation (1): SBP-C error
      = 0.97 * SBP-O error + 0.03 (r = 0.88, P < 0.01); and the Equation (2): PP-C
      error = 0.96 * PP-O error - 0.30 (r = 0.86, P < 0.01). CONCLUSIONS: Noninvasive
      application of the generalized transfer function techniques produces estimates of
      SBP-C and PP-C with errors equivalent to those of the oscillometric blood
      pressure monitor in the estimation of SBP-B and PP-B. The output errors can be
      predicted from input errors of SBP-O and DBP-O.

PMID- 21850063
TI  - Keep it clean.

PMID- 21850064
TI  - China's chemists should avoid the Vanity Fair.

PMID- 21850076
TI  - Brazil revisits forest code.

PMID- 21850077
TI  - HIV drug-prevention strategy carries risks.

PMID- 21850078
TI  - Agencies unveil plans to safeguard science.

PMID- 21850079
TI  - 'Flawed' infant death papers not retracted.

PMID- 21850080
TI  - Drug waste harms fish.

PMID- 21850081
TI  - Apes in Africa: The cultured chimpanzees.

PMID- 21850082
TI  - Death of a pathology centre: Shelved.

PMID- 21850083
TI  - Women in science: In pursuit of female chemists.

PMID- 21850084
TI  - Neuroethics: Give memory-altering drugs a chance.

PMID- 21850089
TI  - Fishery reform: many stocks secure.

PMID- 21850090
TI  - Poaching policy: Rising ivory prices threaten elephants.

PMID- 21850091
TI  - Taxonomy: New name needed for unwise Homo?

PMID- 21850092
TI  - Technology: Nanomaterials need flexible regulation.

PMID- 21850093
TI  - Biotechnology: US Congress right to halt GM salmon.

PMID- 21850094
TI  - Biofuels: Balance the blend of food and fuel.

PMID- 21850095
TI  - Developing world: Endangered cultures need protection too.

PMID- 21850096
TI  - John Marburger (1941-2011).

PMID- 21850097
TI  - Fluid mechanics: When shape matters.

PMID- 21850098
TI  - Stem cells: Orphan receptors find a home.

PMID- 21850099
TI  - Astronomy: Unlocking the secrets of the giant blobs.

PMID- 21850100
TI  - Psychology: When it's fair to share.

PMID- 21850101
TI  - Glaciology: Past ice-shelf collapse in West Antarctica.

PMID- 21850102
TI  - Linguistics: Deep relationships between languages.

PMID- 21850104
TI  - Central powering of the largest Lyman-alpha nebula is revealed by polarized
      radiation.
AB  - High-redshift Lyman-alpha (Lyalpha) blobs are extended, luminous but rare
      structures that seem to be associated with the highest peaks in the matter
      density of the Universe. Their energy output and morphology are similar to those
      of powerful radio galaxies, but the source of the luminosity is unclear. Some
      blobs are associated with ultraviolet or infrared bright galaxies, suggesting an
      extreme starburst event or accretion onto a central black hole. Another
      possibility is gas that is shock-excited by supernovae. But not all blobs are
      associated with galaxies, and these ones may instead be heated by gas falling
      into a dark-matter halo. The polarization of the Lyalpha emission can in
      principle distinguish between these options, but a previous attempt to detect
      this signature returned a null detection. Here we report observations of
      polarized Lyalpha from the blob LAB1 (ref. 2). Although the central region shows
      no measurable polarization, the polarized fraction (P) increases to ~20 per cent
      at a radius of 45 kiloparsecs, forming an almost complete polarized ring. The
      detection of polarized radiation is inconsistent with the in situ production of
      Lyalpha photons, and we conclude that they must have been produced in the
      galaxies hosted within the nebula, and re-scattered by neutral hydrogen.

PMID- 21850106
TI  - Fossil jawless fish from China foreshadows early jawed vertebrate anatomy.
AB  - Most living vertebrates are jawed vertebrates (gnathostomes), and the living
      jawless vertebrates (cyclostomes), hagfishes and lampreys, provide scarce
      information about the profound reorganization of the vertebrate skull during the
      evolutionary origin of jaws. The extinct bony jawless vertebrates, or
      'ostracoderms', are regarded as precursors of jawed vertebrates and provide
      insight into this formative episode in vertebrate evolution. Here, using
      synchrotron radiation X-ray tomography, we describe the cranial anatomy of
      galeaspids, a 435-370-million-year-old 'ostracoderm' group from China and
      Vietnam. The paired nasal sacs of galeaspids are located anterolaterally in the
      braincase, and the hypophyseal duct opens anteriorly towards the oral cavity.
      These three structures (the paired nasal sacs and the hypophyseal duct) were thus
      already independent of each other, like in gnathostomes and unlike in cyclostomes
      and osteostracans (another 'ostracoderm' group), and therefore have the condition
      that current developmental models regard as prerequisites for the development of
      jaws. This indicates that the reorganization of vertebrate cranial anatomy was
      not driven deterministically by the evolutionary origin of jaws but occurred
      stepwise, ultimately allowing the rostral growth of ectomesenchyme that now
      characterizes gnathostome head development.

PMID- 21850105
TI  - Suppression of the coffee-ring effect by shape-dependent capillary interactions.
AB  - When a drop of liquid dries on a solid surface, its suspended particulate matter
      is deposited in ring-like fashion. This phenomenon, known as the coffee-ring
      effect, is familiar to anyone who has observed a drop of coffee dry. During the
      drying process, drop edges become pinned to the substrate, and capillary flow
      outward from the centre of the drop brings suspended particles to the edge as
      evaporation proceeds. After evaporation, suspended particles are left highly
      concentrated along the original drop edge. The coffee-ring effect is manifested
      in systems with diverse constituents, ranging from large colloids to
      nanoparticles and individual molecules. In fact--despite the many practical
      applications for uniform coatings in printing, biology and complex assembly-the
      ubiquitous nature of the effect has made it difficult to avoid. Here we show
      experimentally that the shape of the suspended particles is important and can be
      used to eliminate the coffee-ring effect: ellipsoidal particles are deposited
      uniformly during evaporation. The anisotropic shape of the particles
      significantly deforms interfaces, producing strong interparticle capillary
      interactions. Thus, after the ellipsoids are carried to the air-water interface
      by the same outward flow that causes the coffee-ring effect for spheres, strong
      long-ranged interparticle attractions between ellipsoids lead to the formation of
      loosely packed or arrested structures on the air-water interface. These
      structures prevent the suspended particles from reaching the drop edge and ensure
      uniform deposition. Interestingly, under appropriate conditions, suspensions of
      spheres mixed with a small number of ellipsoids also produce uniform deposition.
      Thus, particle shape provides a convenient parameter to control the deposition of
      particles, without modification of particle or solvent chemistry.

PMID- 21850108
TI  - Benzene.

PMID- 21850109
TI  - Benzidine and dyes metabolized to benzidine: benzidine.

PMID- 21850110
TI  - Benzidine and dyes metabolized to benzidine: dyes metabolized to benzidine
      (benzidine dye class).

PMID- 21850111
TI  - Benzotrichloride.

PMID- 21850112
TI  - Beryllium and beryllium compounds.

PMID- 21850113
TI  - 2,2-Bis(bromomethyl)-1,3-propanediol (technical grade).

PMID- 21850114
TI  - Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether.

PMID- 21850115
TI  - Bromodichloromethane.

PMID- 21850116
TI  - 1,3-Butadiene.

PMID- 21850117
TI  - 1,4-Butanediol dimethanesulfonate.

PMID- 21850118
TI  - Butylated hydroxyanisole.

PMID- 21850119
TI  - Cadmium and cadmium compounds.

PMID- 21850120
TI  - Carbon tetrachloride.

PMID- 21850121
TI  - Ceramic fibers (respirable size).

PMID- 21850122
TI  - Chlorambucil.

PMID- 21850123
TI  - Chloramphenicol.

PMID- 21850124
TI  - Chlorendic acid.

PMID- 21850125
TI  - Chlorinated paraffins (C12, 60% chlorine).

PMID- 21850126
TI  - 3-Chloro-2-methylpropene.

PMID- 21850127
TI  - Chloroform.

PMID- 21850128
TI  - Chloroprene.

PMID- 21850129
TI  - Chromium hexavalent compounds.

PMID- 21850130
TI  - Cisplatin.

PMID- 21850131
TI  - Coal tars and coal-tar pitches.

PMID- 21850132
TI  - Cobalt sulfate.

PMID- 21850133
TI  - Coke-oven emissions.

PMID- 21850134
TI  - p-Cresidine.

PMID- 21850135
TI  - Cupferron.

PMID- 21850136
TI  - Cyclophosphamide.

PMID- 21850137
TI  - Cyclosporin A.

PMID- 21850138
TI  - Dacarbazine.

PMID- 21850139
TI  - Danthron.

PMID- 21850140
TI  - 2,4-Diaminoanisole sulfate.

PMID- 21850141
TI  - 2,4-Diaminotoluene.

PMID- 21850142
TI  - Diazoaminobenzene.

PMID- 21850143
TI  - 2,3-Dibromo-1-propanol.

PMID- 21850144
TI  - 1,4-Dichlorobenzene.

PMID- 21850145
TI  - 3,3'-Dichlorobenzidine and its dihydrochloride.

PMID- 21850146
TI  - Dichlorodiphenyltrichloroethane.

PMID- 21850147
TI  - Dichloromethane.

PMID- 21850148
TI  - 4-Chloro-o-phenylenediamine.

PMID- 21850149
TI  - p-Chloro-o-toluidine and its hydrochloride.

PMID- 21850150
TI  - Twentieth Century Atmospheric Metal Fluxes into Central Park Lake, New York City.
AB  - It is generally assumed that declining atmospheric lead concentrations in urban
      centers during the 1970s and 1980s were due almost entirely to the progressive
      introduction of unleaded gasoline. However, most environmental data are from
      monitoring programs that began only two to three decades ago, which limits their
      usefulness. Here, trace metal and radionuclide data from sediment cores in
      Central Park Lake provide a record of atmospheric pollutant deposition in New
      York City through the 20th century, which suggests that leaded gasoline
      combustion was not the dominant source of atmospheric lead for NYC. Lead
      deposition rates, normalized to known Pb-210 atmospheric influxes, were extremely
      high, reaching maximum values (>70 MUg cm(-2) yr(-1)) from the late 1930s to
      early 1960s, decades before maximum emissions from combustion of leaded gasoline.
      Temporal trends of lead, zinc, and tin deposition derived from the lake sediments
      closely resemble the history of solid waste incineration in New York City.
      Furthermore, widespread use of solid waste incinerators in the United States and
      Europe over the last century suggests that solid waste incineration may have
      provided the dominant source of atmospheric lead and several other metals to many
      urban centers.

PMID- 21850151
TI  - Cracking Down On Youth Tobacco May Influence Drug Use.
AB  - This study evaluated the influence of tobacco Possession-Use-Purchase (PUP) law
      enforcement and illicit drug use and offers. Twenty-four towns were randomly
      assigned into two conditions. Both conditions focused on reducing minors' access
      to commercial sources of tobacco. The communities assigned to the experimental
      condition also increased their PUP law enforcement, whereas among communities in
      the control condition, PUP law enforcement remained at low levels. A Hierarchical
      Linear Modeling analytical approach was selected due to the multilevel data and
      nested design. The likelihood of a child currently using drugs, ever having used
      drugs, or illicit drug offers was lower in the experimental versus control
      conditions. These outcomes suggest that police efforts to reduce specific
      substance use behaviors (i.e., underage tobacco use) may have a positive
      spillover effect and help reduce teen drug use and illicit drug offers.

PMID- 21850152
TI  - Region-based Statistical Analysis of 2D PAGE Images.
AB  - A new comprehensive procedure for statistical analysis of two-dimensional
      polyacrylamide gel electrophoresis (2D PAGE) images is proposed, including
      protein region quantification, normalization and statistical analysis. Protein
      regions are defined by the master watershed map that is obtained from the mean
      gel. By working with these protein regions, the approach bypasses the current
      bottleneck in the analysis of 2D PAGE images: it does not require spot matching.
      Background correction is implemented in each protein region by local
      segmentation. Two-dimensional locally weighted smoothing (LOESS) is proposed to
      remove any systematic bias after quantification of protein regions. Proteins are
      separated into mutually independent sets based on detected correlations, and a
      multivariate analysis is used on each set to detect the group effect. A strategy
      for multiple hypothesis testing based on this multivariate approach combined with
      the usual Benjamini-Hochberg FDR procedure is formulated and applied to the
      differential analysis of 2D PAGE images. Each step in the analytical protocol is
      shown by using an actual dataset. The effectiveness of the proposed methodology
      is shown using simulated gels in comparison with the commercial software packages
      PDQuest and Dymension. We also introduce a new procedure for simulating gel
      images.

PMID- 21850153
TI  - The Meyerhoff Way: How the Meyerhoff Scholarship Program Helps Black Students
      Succeed in the Sciences.
AB  - The Meyerhoff Scholarship Program (MSP) is widely recognized for its
      comprehensive approach of integrating students into the science community. The
      supports provided by the program aim to develop students, primarily Blacks, into
      scientists by offering them academic, social, and professional opportunities to
      achieve their academic and career goals. The current study allowed for a rich
      understanding of the perceptions of current Meyerhoff students and Meyerhoff
      alumni about how the program works. Three groups of MSP students were included in
      the study: 1) new Meyerhoff students participating in Summer Bridge (n=45), 2)
      currently enrolled Meyerhoff students (n=92), and 3) graduates of the MSP who
      were currently enrolled in STEM graduate studies or had completed an advanced
      STEM degree (n=19). Students described the importance of several key aspects of
      the Meyerhoff Scholars Program: financial support, the Summer Bridge Program,
      formation of Meyerhoff identity, belonging to the Meyerhoff family, and
      developing networks - all of which serve to integrate students both academically
      and socially.

PMID- 21850154
TI  - What Good Are Positive Emotions?
AB  - This article opens by noting that positive emotions do not fit existing models of
      emotions. Consequently, a new model is advanced to describe the form and function
      of a subset of positive emotions, including joy, interest, contentment, and love.
      This new model posits that these positive emotions serve to broaden an
      individual's momentary thought-action repertoire, which in turn has the effect of
      building that individual's physical, intellectual, and social resources.
      Empirical evidence to support this broaden-and-build model of positive emotions
      is reviewed, and implications for emotion regulation and health promotion are
      discussed.

PMID- 21850155
TI  - Posttranslational modification of differentially expressed mitochondrial proteins
      in the retina during early experimental autoimmune uveitis.
AB  - PURPOSE: Posttranslational modification of proteins plays an important role in
      cellular functions and is a key event in signal transduction pathways leading to
      oxidative stress and DNA damage. In this study, we used matrix-assisted laser
      desorption/ionization- time of flight (MALDI-TOF) to investigate the
      posttranslational modifications of the differentially expressed proteins in the
      retinal mitochondria during early experimental autoimmune uveitis (EAU). METHODS:
      EAU was induced in 18 B10RIII mice with 25 ug of inter-photoreceptor retinoid
      binding protein (IRBP) emulsified with complete Freund's adjuvant (CFA); 18 mice
      treated with CFA without IRBP served as controls. Retinas were removed from the
      experimental and control groups on day 7 post immunization; mitochondrial
      fractions were extracted and subjected to 2 dimentional-difference in gel
      electrophoresis (2D-DIGE); and the protein spots indicating differential
      expression were subjected to MALDI-TOF for protein identification and indication
      of any posttranslational modifications. RESULTS: Of the 13 proteins found to be
      differentially expressed by 2D-DIGE (including upregulated aconitase,
      mitochondrial heat shock protein (mtHsp) 70, lamin-1, syntaxin-binding protein,
      alphaA crystallin, betaB2 crystallin, along with downregulated guanine nucleotide
      binding protein and ATP synthase) nine were found to undergo posttranslational
      modification. Oxidation was a common modification found to occur on aconitase,
      mtHsp 70, ATP synthase, lamin-1, betaB2-crystallin, guanine nucleotide-binding
      protein, and manganese superoxide dismutase (MnSOD). In addition, aconitase
      hydratase, mtHsp 70, guanine nucleotide-binding protein, ATP synthase, syntaxin
      binding protein, betaB2-crystallin, and lamin-1 were also modified by
      carbamidomethylation. alphaA-crystallin had a pyro-glu modification. CONCLUSIONS:
      Several proteins present in the retinal mitochondria are posttranslationally
      modified during early EAU, indicating the presence of oxidative stress and
      mitochondrial DNA damage. The most common modifications are oxidation and
      carbamidomethylation. A better understanding of the proteins susceptible to
      posttranslational modifications in the mitochondria at the early stage of the
      disease may serve to advance therapeutic interventions to attenuate disease
      progression.

PMID- 21850156
TI  - Increased tumor necrosis factor-alpha, cleaved caspase 3 levels and insulin
      receptor substrate-1 phosphorylation in the beta1-adrenergic receptor knockout
      mouse.
AB  - PURPOSE: To investigate the role of beta1-adrenergic receptors on insulin like
      growth factor (IGF)-1 receptor signaling and apoptosis in the retina using beta1
      adrenergic receptor knockout (KO) mice. METHODS: Western blotting and enzyme
      linked immunosorbent assay analyses were done on whole retinal lysates from beta1
      adrenergic receptor KO mice and wild-type littermates. In addition, vascular
      analyses of degenerate capillaries and pericyte ghosts were done on the retina of
      the beta1-adrenergic receptor KO mice versus littermates. RESULTS: Lack of beta1
      adrenergic receptors produced a significant increase in both degenerate
      capillaries and pericyte ghosts. This was accompanied by an increase in cleaved
      caspase 3 and tumor necrosis factor alpha levels. IGF-1 receptor phosphorylation
      was not changed; however, protein kinase B (Akt) phosphorylation was
      significantly decreased. The decrease in Akt phosphorylation is likely caused by
      increased insulin receptor substrate-1 serine 307 (IRS-1(Ser307))
      phosphorylation, which is inhibitory to IGF-1 receptor signaling. CONCLUSIONS:
      These studies further support the idea that maintenance of beta-adrenergic
      receptor signaling is beneficial for retinal homeostasis. Loss of beta1
      adrenergic receptor signaling alters tumor necrosis factor alpha and apoptosis
      levels in the retina, as well as Akt and IGF-1 receptor phosphorylation. Since
      many of these same changes are observed in the diabetic retina, these data
      support that novel beta-adrenergic receptor agents may provide additional avenues
      for therapeutics.

PMID- 21850157
TI  - High-mobility group box-1 and biomarkers of inflammation in the vitreous from
      patients with proliferative diabetic retinopathy.
AB  - PURPOSE: To measure levels of high-mobility group box -1 (HMGB1) and soluble
      receptor for advanced glycation end products (sRAGE) in the vitreous fluid from
      patients with proliferative diabetic retinopathy (PDR) and to correlate their
      levels with clinical disease activity and the levels of the inflammatory
      biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular
      adhesion molecule-1 (sICAM-1), interleukin-1beta (IL-1beta), and granulocyte
      macrophage colony-stimulating factor (GM-CSF). In addition, we examined the
      expression of HMGB1 in the retinas of diabetic mice. METHODS: Vitreous samples
      from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked
      immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis
      and western blotting. RESULTS: HMGB1 was detected in all vitreous samples and
      sRAGE was detected in 5 PDR samples. IL-1beta was detected in 3PDR samples and GM
      CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization
      were twofold and threefold higher than that in inactive PDR and nondiabetic
      patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were
      significantly higher than those in PDR patients without hemorrhage and
      nondiabetic patients (p=0.0111). There were significant correlations between
      levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548,
      p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice.
      CONCLUSIONS: Subclinical chronic inflammation might contribute to the progression
      of PDR.

PMID- 21850158
TI  - Photo-products of retinal pigment epithelial bisretinoids react with cellular
      thiols.
AB  - PURPOSE: Bisretinoids such as A2E that accumulate as components of the lipofuscin
      of retinal pigment epithelial cells are implicated in some retinal disease
      processes. These compounds undergo light-induced oxidation and cleavage with the
      latter releasing of a mixture of aldehyde-bearing fragments, including dicarbonyl
      methylglyoxal. We tested for the reactivity of photooxidation and
      photodegradation products of A2E with thiol-containing glutathione (GSH).
      METHODS: In cell-free assays, we measured the ability of photooxo-A2E to
      competitively inhibit the GSH-mediated reduction of the thiol reagent 5,5'
      dithiobis-(2-nitrobenzoic acid). Cellular GSH was assayed colorimetrically.
      Products of GSH reduction and GSH-adducts were detected by electrospray
      ionization mass spectrometry (ESI-MS) and GSH and oxidized GSH (glutathione
      disulfide [GSSG]) were quantified from chromatographic peak areas. RESULTS: We
      found that GSH can donate hydrogen atoms to, and form conjugates with,
      photooxidized forms of the bisretinoid A2E and with its photocleavage products.
      Reaction with non-photooxidized A2E was not observed. Chemical reduction by GSH
      involved the donation of a hydrogen atom from each of two GSHs. The ratio of GSH
      consumed to GSSG formed was consistent with GSH being used for both reduction and
      adduct formation. With the aid of synthesized standards, methylglyoxal-GSH
      adducts were identified within mixtures of GSH and photooxidized A2E; the adducts
      formed noncatalytically and by glutathione-S-transferase mediation. CONCLUSIONS:
      Reduction and adduct formation by GSH likely limits the reactivity of bisretinoid
      photoproducts and may aid their elimination from the cells. These findings are
      significant to forms of macular degeneration associated with bisretinoid
      formation and maculopathy stemming from GSH synthase deficiency.

PMID- 21850159
TI  - Mutations in a novel serine protease PRSS56 in families with nanophthalmos.
AB  - PURPOSE: Nanophthalmos is a rare genetic ocular disorder in which the eyes of
      affected individuals are abnormally small. Patients suffer from severe hyperopia
      as a result of their markedly reduced axial lengths, but otherwise are capable of
      seeing well unlike other more general forms of microphthalmia. To date one gene
      for nanophthalmos has been identified, encoding the membrane-type frizzled
      related protein MFRP. Identification of additional genes for nanophthalmos will
      improve our understanding of normal developmental regulation of eye growth.
      METHODS: We ascertained a cohort of families from eastern Canada and Mexico with
      familial nanophthalmos. We performed high density microsatellite and high density
      single nucleotide polymorphism (SNP) genotyping to identify potential chromosomal
      regions of linkage. We sequenced coding regions of genes in the linked interval
      by traditional PCR-based Sanger capillary electrophoresis methods. We cloned and
      sequenced a novel cDNA from a putative causal gene to verify gene structure.
      RESULTS: We identified a linked locus on chromosome 2q37 with a peak logarithm
      (base 10) of odds (LOD) score of 4.7. Sequencing of coding exons of all genes in
      the region identified multiple segregating variants in one gene, recently
      annotated as serine protease gene (PRSS56), coding for a predicted trypsin serine
      protease-like protein. One of our families was homozygous for a predicted
      pathogenic missense mutation, one family was compound heterozygous for two
      predicted pathogenic missense mutations, and one family was compound heterozygous
      for a predicted pathogenic missense mutation plus a frameshift leading to
      obligatory truncation of the predicted protein. The PRSS56 gene structure in
      public databases is based on a virtual transcript assembled from overlapping
      incomplete cDNA clones; we have now validated the structure of a full-length
      transcript from embryonic mouse brain RNA. CONCLUSIONS: PRSS56 is a good
      candidate for the causal gene for nanophthalmos in our families.

PMID- 21850161
TI  - Retinal nerve fiber hypertrophy in ataxia of Charlevoix-Saguenay patients.
AB  - PURPOSE: To present full ophthalmologic examination and retinal nerve fiber layer
      (RNFL) photographs of autosomal recessive spastic ataxia of Charlevoix-Saguenay
      (ARSACS) patients showing significant increases in RNFL thickness compared to
      healthy subjects, but without myelinated retinal fibers. METHODS: The study
      design was observational case series. Ten eyes of five patients with molecular
      confirmation of ARSACS underwent a full ophthalmologic examination that included
      clinical history, visual acuity, biomicroscopy of the anterior segment,
      gonioscopy, Goldmann applanation tonometry, central corneal ultrasonic
      pachymetry, ophthalmoscopy of the posterior segment, standard automatic perimetry
      (Humphrey field), simultaneous stereophotographs of the optic disc after
      mydriasis, a series of five red-free digital fundus photographs for RNFL
      evaluation, topographic analysis of the optic disc using the Heidelberg retina
      tomography, and measurement of peripapillary RNFL thickness with Cirrus optical
      coherence tomography. RESULTS: All patients showed abnormal visual fields, normal
      optic discs with a mild to strikingly increased visibility of RNFL in color
      stereophotographs, normal Heidelberg tomography, and moderate to markedly
      increased RNFL thickness in Cirrus tomography (average thickness ranging from 119
      MUm to 220 MUm). CONCLUSIONS: We found evidence of RNFL hypertrophy in ARSACS
      patients that may have been interpreted as hypermyelinated retinal fibers in
      previous reports. A revision of ARSACS diagnostic criteria, particularly with
      regard to retinal alterations, is necessary.

PMID- 21850160
TI  - Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens
      protein turbidity and selenite-induced cataractogenesis in vivo.
AB  - PURPOSE: In this study, we investigated the biochemical pharmacology of
      pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet
      (UV)-induced lens protein turbidity challenges. The systemic effects of catalin
      were determined using a selenite-induced cataractogenesis rat model. METHODS: In
      vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens
      crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity
      of lens crystallin solutions) were used to screen the activity of PRX and catalin
      eye drop solutions. Turbidity was identified as the optical density measured
      using spectroscopy at 405 nm. We also determined the in vivo effects of catalin
      on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was applied to analyze the
      integrity of crystallin samples. RESULTS: PRX at 1,000 MUM significantly delayed
      UVC-induced turbidity formation compared to controls after 4 h of UVC exposure
      (p<0.05), but not in groups incubated with PRX concentrations of <1,000 MUM.
      Results were further confirmed by SDS-PAGE. The absolute gamma-crystallin
      turbidity induced by 4 h of UVC exposure was ameliorated in the presence of
      catalin equivalent to 1~100 MUM PRX in a concentration-dependent manner. Samples
      with catalin-formulated vehicle only (CataV) and those containing PRX equivalent
      to 100 MUM had a similar protective effect after 4 h of UVC exposure compared to
      the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 MUM significantly delayed 10 mM
      selenite- and calcium-induced turbidity formation compared to controls on days
      0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 MUM PRX) had an initial
      protective effect against selenite-induced lens protein turbidity on day 1
      (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically
      decreased the mean cataract scores in selenite-induced cataract rats on post
      induction day 3 compared to the controls (1.3+/-0.2 versus 2.4+/-0.4; p<0.05).
      However, catalin (equivalent to up to 100 MUM PRX) did not inhibit calpain
      induced proteolysis activated by calcium, and neither did 100 MUM PRX.
      CONCLUSIONS: PRX at micromolar levels ameliorated selenite- and calcium-induced
      lens protein turbidity but required millimolar levels to protect against UVC
      irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins
      by catalin at micromolar concentrations may have been a result of the catalin
      formulated vehicle. Transient protection by catalin against selenite-induced
      turbidity of crystallin solutions in vitro was supported by the ameliorated
      cataract scores in the early stage of cataractogenesis in vivo by subcutaneously
      administered catalin. PRX could not inhibit calpain-induced proteolysis activated
      by calcium or catalin itself, and may be detrimental to crystallins under UVB
      exposure. Further studies on formulation modifications of catalin and recommended
      doses of PRX to optimize clinical efficacy by cataract type are warranted.

PMID- 21850162
TI  - Rho-Rho kinase pathway in the actomyosin contraction and cell-matrix adhesion in
      immortalized human trabecular meshwork cells.
AB  - PURPOSE: The outflow facility for aqueous humor across the trabecular meshwork
      (TM) is enhanced by agents that oppose the actomyosin contraction of its resident
      cells. Phosphorylation of MYPT1 (myosin light chain [MLC] phosphatase complex of
      Type 1) at Thr853 and Thr696 inhibits dephosphorylation of MLC, leading to an
      increase in actomyosin contraction. In this study, we examined the effects of Rho
      kinase (ROCK) inhibitors on the relative dephosphorylation of the two sites of
      MYPT1 using human TM cells (GTM3). METHODS: Dephosphorylation of MYPT1 at Thr853
      and Thr696 was determined by western blot analysis following exposure to
      selective inhibitors of ROCK, namely Y-27632 and Y-39983. Consequent
      dephosphorylation of MLC and decreases in actomyosin contraction were assessed by
      western blot analysis and collagen gel contraction assay, respectively. Changes
      in the cell-matrix adhesion were measured in real time by electric cell-substrate
      impedance sensing and also assessed by staining for paxillin, vinculin, and focal
      adhesion kinase (FAK). RESULTS: Both ROCK inhibitors produced a concentration
      dependent dephosphorylation at Thr853 and Thr696 of MYPT1 in adherent GTM3 cells.
      IC50 values for Y-39983 were 15 nM and 177 nM for dephosphorylation at Thr853 and
      Thr696, respectively. Corresponding values for Y-27632 were 658 nM and 2270 nM.
      Analysis of the same samples showed a decrease in MLC phosphorylation with IC50
      values of 14 nM and 1065 nM for Y-39983 and Y-27632, respectively. Consistent
      with these changes, both inhibitors opposed contraction of collagen gels induced
      by TM cells. Exposure of cells to the inhibitors led to a decrease in the
      electrical cell-substrate resistance, with the effect of Y-39983 being more
      pronounced than Y-27632. Treatment with these ROCK inhibitors also showed a loss
      of stress fibers and a concomitant decrease in tyrosine phosphorylation of
      paxillin and FAK. CONCLUSIONS: Y-39983 and Y-27632 oppose ROCK-dependent
      phosphorylation of MYPT1 predominantly at Thr853 with a corresponding decrease in
      MLC phosphorylation. A relatively low effect of both ROCK inhibitors at Thr696
      suggests a role for other Ser/Thr kinases at this site. Y-39983 was several-fold
      more potent when compared with Y-27632 at inhibiting the phosphorylation of MYPT1
      at either Thr853 or Thr696 commensurate with its greater potency at inhibiting
      the activity of human ROCK-I and ROCK-II enzymes.

PMID- 21850163
TI  - Alterations in the aqueous humor proteome in patients with a glaucoma shunt
      device.
AB  - PURPOSE: To investigate whether implantation of a glaucoma shunt device leads to
      inappropriate accumulation of plasma derived proteins in the aqueous humor.
      METHODS: Aqueous humor samples were collected from 11 patients (study group) with
      a glaucoma shunt device undergoing either cataract surgery or a corneal
      transplant and 11 patients (control) with senile cataract undergoing routine
      cataract extraction. Of the study group, 9 had an Ahmed valve implant and 2 eyes
      had a Baerveldt implant. Tryptic digests of the mixture of proteins in aqueous
      humor (AH) were analyzed using Liquid Chromatography/Mass Spectrometry (LC
      MS/MS). Proteins were identified with high confidence using stringent criteria
      and compared quantitatively using a label-free platform (IdentiQuantXLTM).
      RESULTS: We identified 135 proteins in the albumin-depleted fraction in both the
      study and control group AH. Using stringent criteria, 13 proteins were detected
      at a significantly higher level compared to controls. These proteins are known to
      play a role in oxidative stress, apoptosis, inflammation and/or immunity and
      include gelsolin (p=0.00005), plasminogen (p=0.00009), angiotensinogen
      (p=0.0001), apolipoprotein A-II (p=0.0002), beta-2-microglobulin (p=0.0002),
      dickkopf-3 (DKK-3; p=0.0002), pigment epithelium-derived factor (p=0.0002), RIG
      like 7-1 (p=0.0002), afamin (p=0.0003), fibronectin 1 (FN1; p=0.0003),
      apolipoprotein A-I (p=0.0004), activated complement C4 protein (C4a; p=0.0004)
      and prothrombin (p=0.0004). Many of the identified proteins were novel proteins
      that have not been associated with glaucoma in prior studies. All but C4a
      (complement C4 is a plasma protein but not in an activated form) are known plasma
      proteins and the elevated levels of these proteins in the aqueous humor suggests
      a breach in the blood-aqueous barrier with passive influx into the anterior
      chamber of the eye. CONCLUSIONS: The presence of these proteins in the aqueous
      humor suggests that glaucoma shunt device causes either a breach in blood-aqueous
      barrier or chronic trauma, increasing influx of oxidative, apoptotic and
      inflammatory proteins that could potentially cause corneal endothelial damage.

PMID- 21850164
TI  - A robust model for simultaneously inducing corneal neovascularization and retinal
      gliosis in the mouse eye.
AB  - PURPOSE: To develop an animal model for simultaneously eliciting corneal
      angiogenesis and retinal gliosis that will enable the assessment of inhibitor
      efficacy on these two pathological processes in separate anatomic sites of the
      ocular globe. METHODS: Four to six week-old mice in a C57BL/6J background were
      anesthetized and 0.15 N NaOH was applied to the cornea, followed by mechanical
      scraping of the epithelium from limbus and central cornea. After this injury,
      mice were treated with vehicle or with an inhibitor (withaferin A [WFA]), which
      were delivered by intraperitoneal injection, to assess the pharmacological
      effects on angiogenesis and/or gliosis. Mice were sacrificed after 14 days and
      tissues (corneas and retinas) were prepared for analysis of corneal
      neovascularization and retinal gliosis by immunohistochemistry and western
      blotting, respectively. This protocol was also suited for studying earlier
      disease end points, for assessment of drug dose efficacy or genetic influences
      and the entire procedure and this analysis was completed in 16-17 days. RESULTS:
      Both corneal angiogenesis and retinal gliosis were maximally sustained at
      fourteen days following chemical and mechanical injury of the cornea. 1) Injured
      corneas showed abundant CD31+ staining, with new blood vessels branching out from
      the limbus to the central cornea. WFA treatment potently inhibited corneal
      neovascularization. 2) Retinal gliosis in injured mice was associated with
      upregulated expression of glial fibrillary acidic protein (GFAP) that appeared as
      polymeric filaments and soluble forms expressed in reactive Muller glial cells.
      WFA treatment potently downregulated the expression of soluble and filamentous
      GFAP; the latter protein was fragmented. CONCLUSIONS: We have developed a mouse
      model for investigating retinal gliosis and corneal neovascularization. We used
      this model to demonstrate the simultaneous inhibitory effects of WFA on both of
      these disease processes. Retinal gliosis occurs in several major degenerative
      conditions of the eye, including age-related macular degeneration, where
      angiogenesis is also a prevailing pathological feature. Thus, inhibitors of both
      gliosis and angiogensis used as combination therapy are currently being explored
      for treatment of such complex diseases. The model presented here affords a very
      simple preclinical assay for screening combination of drugs or
      polypharmacological agents and reduces the numbers of animals because of the
      different anatomic sites of these pathologies. Finally, given that endogenous
      mediators elicit angiogenesis and gliosis in this model, the combination of
      genetics and pharmacology can be exploited to study drug mechanisms and for
      target validation in vivo.

PMID- 21850165
TI  - Tectonic lamellar keratoplasty with acellular corneal stroma in high-risk corneal
      transplantation.
AB  - PURPOSE: Tectonic lamellar keratoplasty (TLKP) is a primary surgical procedure to
      improve the condition of the recipient bed in high-risk corneal transplantation.
      It is usually performed for a secondary optical penetrating keratoplasty (PKP).
      The present study was undertaken to explore a new strategy for TLKP using
      acellular corneal stroma (ACS) prepared by decellularization. METHODS: ACS for
      TLKP was prepared from cat cornea by decellularization. The efficiency of the
      decellularization was examined by hematoxylin and eosin (H&E) staining and
      through DNA content analysis. Twenty-eight New Zealand white rabbits, as
      recipients, were assigned to one of two groups that had different material for
      their TLKP. The TLKP was combined with a central optical PKP as a single-stage
      procedure. Either ACS or fresh cat corneal lamella, 11.25 mm in diameter, was
      used for the TLKP in these two groups. After TLKP, a 6.5-mm full-thickness cat
      cornea was placed in the central cornea of each recipient rabbit for PKP.
      Clinical outcomes and the histology of the transplants were compared post
      operatively. RESULTS: ACS for TLKP prolonged the survival of the transplants. The
      mean survival time of the transplants in the ACS group (36.4+/-4.3 days) was
      longer than for those in the control group (14.0+/-2.2 days, p<0.05). The ACS
      group showed a significantly smaller neovascularization area compared to the
      control group. The areas of corneal neovascularization were 5.3+/-1.1 mm2 and
      45.2+/-4.9 mm2 (p<0.05), respectively, after two weeks, and 25.1+/-4.7 mm2 and
      105.3+/-12.4 mm2 (p<0.05), respectively, after four weeks. Histology revealed
      that fewer inflammatory cells were infiltrating the transplants in the ACS group
      than those in the control group. CONCLUSIONS: The use of ACS for TLKP prolonged
      the survival of corneal transplants, reduced corneal neovascularization, and
      prevented from infiltration of inflammatory cells. It is a feasible and effective
      strategy to prolong the survival of transplants in high-risk corneal
      transplantation.

PMID- 21850166
TI  - Comparison of the antiangiogenic activity of modified RGDRGD-endostatin to
      endostatin delivered by gene transfer in vivo rabbit neovascularization model.
AB  - PURPOSE: Endostatin plays an important role in inhibiting corneal
      neovascularization (CNV). The aim of this study was to evaluate the
      antiangiogenic activities of lipid-mediated subconjunctival injection of the
      modified RGDRGD (arginine- glycin- aspartic- arginine- glycin- aspartic-
      endostatin gene in a rabbit model of neovascularization in vivo. METHODS: A
      modified human endostatin gene containing an RGDRGD motif was obtained by rapid
      site-directed mutagenesis. Forty New Zealand white rabbits underwent alkaline
      burn and developed CNV, which were randomly divided into four groups: an
      experimental control group, a PCI empty vector group, a PCI-endostatin group, and
      a PCI-RGDRGD-endostatin group. The vector, endostatin, and RGDRGD-endostatin
      groups received injections into the superior bulbar conjunctiva after the burn.
      An injection of 5 MUg was given twice at 1-week intervals. Four eyes of two
      rabbits received neither treatment nor alkaline burn and served as absolute
      normal controls. The areas of CNV were monitored after 7 and 14 days. Corneas
      were examined by histology, and VEGF (vascular endothelial growth factor) and
      CD31 (platelet endothelial cell adhesion molecule-1) expression was detected by
      immunohistochemistry after 7 and 14 days. Retina, liver, and kidney were examined
      by histology, and CD38 expression in the inflammatory cells was detected by
      immunohistochemistry at 90 days. RESULTS: Subconjunctival injection of both
      native endostatin and modified RGDRGD-endostatin genes resulted in a significant
      suppression of CNV in vivo, with modified RGDRGD-endostatin being more effective
      than native endostatin. The mean concentration of VEGF in the PCI-RGDRGD
      endostatin group significantly decreased compared to the means in the other
      groups. Upon histological examination, the endostatin-treated and RGDRGD
      endostatin-treated eyes showed significantly less neovascular area and fewer
      vessels than the control and vector-injected groups. Retinal, hepatic, and renal
      tissue sections were normal, and there was no inflammatory cell infiltration
      observed. CONCLUSIONS: Native and modified endostatin can significantly inhibit
      CNV by suppressing the expression of VEGF. However, modified endostatin with the
      RGDRGD motif is far more effective than the endostatin gene in antiangiogenic
      activity.

PMID- 21850167
TI  - c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail-patella
      syndrome associated with glaucoma.
AB  - PURPOSE: To report the clinical, ophthalmic, extraophthalmic, and genetic
      characteristics of nail-patella syndrome (NPS) in a Chilean family and to
      investigate the expressivity of open angle glaucoma (OAG) and ocular hypertension
      (OHT) in the family members. METHODS: Five family members affected with NPS and
      two unaffected members underwent a complete ophthalmologic examination, including
      computerized visual field, optical coherence tomography (OCT) of the optic disc
      and ultrasound pachymetry. Renal function was assessed by urinalysis and blood
      tests. Orthopedic evaluations were also performed, including radiological studies
      of the wrist, elbow and hip joints. Genomic DNA was extracted from peripheral
      leukocytes of the five affected and two unaffected family members. Exons 2-6 of
      the LIM homeobox transcription factor 1-beta (LMX1B) gene were screened for
      mutations by DNA sequencing of the proband. We also screened for mutations in
      exon 2 by polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) of the other participants and 91 blood donors. RESULTS: Five living family
      members from three generations were positively diagnosed with NPS, three of them
      with varying degrees of OAG and one with OHT. Retinal nerve fiber layer (RNFL)
      thickness measured by spectral domain OCT was below normal values in three
      individuals. All subjects evaluated had normal nephrologic function. Orthopedic,
      clinical, and radiological alterations were compatible with NPS. Screening for
      mutations in exons 2- 6 of LMX1B showed a heterozygous missense mutation c.194
      A>C changing glutamine to proline within exon 2 in codon 65 (Q65P) of the coding
      sequence. This mutation was present in all NPS subjects and absent in the
      unaffected family members and in 91 Chilean blood donors. CONCLUSIONS: This is
      the first report of c.194 A>C mutation in LMX1B in a Chilean family with NPS and
      the second worldwide. The phenotype associated with this mutation is variable
      within the family, although we noted a close connection between the presence of
      the c.194 A>C mutation and the presence of OHT or OAG and probably also with an
      early onset of OHT in patients with NPS. All subjects older than 21 years had
      either OHT or OAG. We also suggest that the LMX1B mutation may be related to
      affective disorders.

PMID- 21850168
TI  - Identification of a novel LCA5 mutation in a Pakistani family with Leber
      congenital amaurosis and cataracts.
AB  - PURPOSE: To determine the cause of Leber congenital amaurosis (LCA) and
      developmental cataracts in a consanguineous Pakistani family. METHODS: The
      diagnosis was established in all affected individuals of a Pakistani LCA family
      by medical history, funduscopy, and standard ERG. We performed genome-wide
      linkage analysis for mapping the disease locus in this family. RESULTS:
      Congenitally severely reduced visual acuity and nystagmus were reported for all
      patients who, in the later phase of the disease, also developed cataracts. LCA in
      the family cosegregated with homozygosity for a single nucleotide polymorphism
      (SNP) haplotype on chromosome 6p14.1. The respective candidate region contained
      Leber congenital amaurosis 5 (LCA5), a gene previously reported to underlie LCA.
      We subsequently identified a novel truncating mutation in exon 4 of LCA5,
      c.642delC, in homozygous state in all affected persons of the family.
      CONCLUSIONS: We report a novel LCA5 mutation causing LCA in a Pakistani family.
      Developmental cataracts were present in two of the four patients, raising the
      possibility that LCA5 mutations may predispose to this additional ocular
      pathology.

PMID- 21850169
TI  - Intravitreal homocysteine-thiolactone injection leads to the degeneration of
      multiple retinal cells, including photoreceptors.
AB  - PURPOSE: Hyperhomocysteinemia is known to cause degeneration of retinal ganglion
      cells, but its influence on photoreceptors remains largely unknown. In
      particular, the role of homocysteine-thiolactone (Hcy-T)--the physiologic
      metabolite of homocysteine that has been proven to be more cytotoxic than
      homocysteine itself--as a factor that causes retinopathy, has not been defined.
      This study aimed to investigate the toxic effects of excessive Hcy-T in a mouse
      model. METHODS: A total of 60 six-week-old female ICR mice were used in this
      study. The mice were divided into 3 experimental groups and 2 control groups. The
      mice in the experimental groups were subjected to intravitreal injections of Hcy
      T to reach final estimated intravitreal concentrations at 5, 25, and 200 MUM,
      respectively. Mice without injection (blank) and with 0.9 NaCl injections (sham
      injection) were used as controls. The mice with 200 MUM Hcy-T were sacrificed at
      days 7, 15, 45, and 90 after injection and the mice with 5 or 25 MUM Hcy-T were
      sacrificed at day 90, with the controls sacrificed at day 15 or 90 for
      comparison. Semi-quantitative dot-blot analysis was performed for confirmation of
      retinal homocysteinylation. The mouse retinas were evaluated microscopically,
      with the thickness of total and specific retinal layers determined.
      Immunohistochemical analysis was performed and the labeled cells were quantified
      to determine the effects of excessive Hcy-T on specific retinal cells. RESULTS:
      Dose-dependent retinal homocysteinylation after Hcy-T injection was confirmed.
      The homocysteinylation was localized in the outer and inner segments of
      photoreceptors and the ganglion cell layer (GCL). Retinal cell degenerations were
      found in the GCL, inner nuclear layer, and outer nuclear layer at day 90 after
      200 uM Hcy-T injection. Significant thickness reduction was found in the total
      retina, outer nuclear layer, and the outer and inner segment layers. A trend of
      thickness reduction was also found in the GCL and inner nuclear layer, although
      this was not statistically significant. The rhodopsin+ photoreceptors and the
      calbindin+ horizontal cells were significantly reduced at day 15, and were nearly
      ablated at day 90 after 200 MUM Hcy-T injection (p<0.001 for both day 15 and day
      90), which was not seen in the sham injection controls. The Chx-10+ or the Islet
      1+ bipolar cells and the Pax-6+ amacrine cells were severely misarranged at day
      90, but no significant reduction was found for both cell types. The GFAP+ Muller
      cells were activated at day 15, but were not significantly increased at day 90
      after the injection. CONCLUSIONS: Excessive retinal homocysteinylation by Hcy-T,
      a condition of hyperhomocysteinemia, could lead to degeneration of
      photoreceptors, which might lead to retinopathies associated with severe
      hyperhomocysteinemia or diabetes mellitus.

PMID- 21850171
TI  - Molecular screening of the CYP4V2 gene in Bietti crystalline dystrophy that is
      associated with choroidal neovascularization.
AB  - PURPOSE: Bietti crystalline dystrophy (BCD) is an autosomal recessive disease
      characterized by intraretinal deposits of multiple small crystals, with or
      without associated crystal deposits in the cornea. The disease is caused by
      mutation in the cytochrome p450, family 4, subfamily v, polypeptide 2 (CYP4V2)
      gene. Choroidal neovascularization (CNV) is a rare event in BCD. We report two
      cases of BCD associated with CNV. CYP4V2 and exon 5 of tissue inhibitor of
      metalloproteinase 3 (TIMP3) were screened in both cases. A patient with BCD, but
      without CNV, was also screened to identify pathogenic variations. METHODS: Three
      BCD families of Asian Indian origin were recruited after a comprehensive
      ophthalmic examination. Genomic DNA was isolated from blood leukocytes, and
      coding exons and flanking introns of CYP4V2 and exon 5 of TIMP3 were amplified
      via polymerase chain reaction (PCR) and were sequenced. Family segregation,
      control screening, and bioinformatics tools were used to assess the pathogenicity
      of the novel variations. RESULTS: Of the three BCD patients, two had parafoveal
      CNV. The patient with BCD, but without CNV had novel single base-pair duplication
      (c.1062_1063dupA). This mutation results in a structurally defective and unstable
      protein with impaired protein function. Four novel benign variations (three in
      exons and one in an intron) were observed in the cohort. Screening of exon 5 of
      TIMP3 did not reveal any variation in these families. CONCLUSIONS: A novel
      mutation was found in a patient with BCD but without CNV, while patients with BCD
      and CNV did not show any pathogenic variation. The modifier role of TIMP3 in the
      pathogenesis of CNV in BCD was partly ruled out, as no variation was observed in
      exon 5 of the gene. A larger BCD cohort with CNV needs to be studied and screened
      to understand the genetics of CNV in BCD.

PMID- 21850170
TI  - Co-variation of STI1 and WDR36/UTP21 alters cell proliferation in a glaucoma
      model.
AB  - PURPOSE: To investigate the role of multigenic variation in primary open-angle
      glaucoma (POAG) involving the rRNA processing gene WD repeat domain 36 (WDR36).
      METHODS: We examined the heat shock protein 70/90 (HSP70/90)-organizing co
      chaperone stress-induced-phosphoprotein 1 (STI1) as a potential co-modifying gene
      in glaucoma patients found to harbor WDR36 amino acid variation. The STI1 gene
      was sequenced and its POAG-associated amino acid variant K434R, as well as the
      single nucleotide polymorphism (SNP) P173T, were tested for functional defects in
      a yeast model system previously used to characterize WDR36 variants (using the
      homologous yeast gene U3 protein 21 [UTP21]). RESULTS: A POAG patient
      heterozygous for the WDR36 variant L25P was discovered to also carry the STI1
      variant K434R in a heterozygous state. Variant K434R, located at an
      evolutionarily-conserved site, was not found in a pool of clinically-examined
      individuals lacking WDR36 variation which included 55 normal controls and 20
      patients with normal tension glaucoma (NTG). STI1 (K434R) and the homologous
      yeast variant K470R were able to rescue yeast growth-inhibition by the HSP90
      inhibitor radicicol. Double mutant haploid strains expressing human STI1 (K434R)
      and recombinant yeast UTP21 variants did not have significantly different levels
      of 18S rRNA from the corresponding hSTI1 (WT) strains. However, specific double
      mutant K434R strains exhibited significantly slower culture growth at 37  degrees
      C. Double mutant P173T strains also displayed altered growth rates at 37  degrees
      C. CONCLUSIONS: STI1 variation does not play a significant direct role in the
      genetics of POAG. However, as previously found for the STI1 null allele, non
      synonymous variants of human STI1 confer growth dysregulation in the context of
      specific yeast UTP21 mutations and heat stress. Based on the genetic association
      of two co-heterozygous STI1 and WDR36 variants in a POAG patient and the
      functional analyses performed in a model system for basic eukaryotic cellular
      processes, these experiments point to a conserved molecular pathway involving
      STI1 and WDR36.

PMID- 21850172
TI  - Horizontal gaze palsy with progressive scoliosis: three novel ROBO3 mutations and
      descriptions of the phenotypes of four patients.
AB  - PURPOSE: Clinical and molecular characterization of patients with horizontal gaze
      palsy with progressive scoliosis (HGPPS) to extend existing knowledge of the
      phenotype caused by mutations in the Roundabout homolog of Drosophila 3 (ROBO3)
      gene. METHODS: Four patients (aged 6 months to 13 years), two of them siblings,
      with features of horizontal gaze palsy and their parents were examined clinically
      and by molecular testing of the ROBO3 gene. The three families were unrelated,
      but parents in each family were consanguineous. RESULTS: We identified three
      novel homozygous ROBO3 mutations in four patients with typical ophthalmologic
      signs of HGPPS. We found an exonic insertion/deletion mutation (c.913delAinsTGC;
      p.Ile305CysfsX13), a 31 bp deletion including the donor splice site of exon 17
      and adjacent exonic and intronic sequences (c.2769_2779del11, 2779+1_+20del20),
      and a missense mutation located next to a splice donor site (c.3319A>C) resulting
      in skipping of exon 22, as shown by cDNA analysis. CONCLUSIONS: We describe three
      novel mutations in the ROBO3 gene and the detailed clinical phenotype of HGPPS.
      One patient displayed marked convergence upon attempting smooth pursuits to both
      sides. In one patient, the typical ophthalmologic phenotype, the neuroradiologic
      findings, and molecular testing led to the diagnosis even before scoliosis
      developed. In addition to the typical magnetic resonance imaging brain signs of
      HGPPS, this patient had marked hypoplasia of the frontal lobes and corpus
      callosum. In summary, diagnosis of HGPPS may be established by ophthalmologic and
      molecular investigation early in life, allowing ongoing orthopedic surveillance
      from an early stage.

PMID- 21850173
TI  - Effects of 17beta-estradiol on proliferation, cell viability and intracellular
      redox status in native human lens epithelial cells.
AB  - PURPOSE: The purpose of this study was to examine the effects of 17beta-estradiol
      on proliferation, cell death and redox status in cultured human lens epithelial
      cells (HLECs). METHODS: HLECs were exposed to 17beta-estradiol after which cell
      viability was measured by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium
      bromide (MTT) and the number of mitotic and apoptotic cell nuclei was determined
      after staining with Hoechst 33342. Apoptosis was also determined by measuring
      caspase-3 activity and propidium iodide was used to determine the proportion of
      non-viable cells. Pro- and antioxidative effects of 17beta-estradiol was
      investigated by measuring peroxides, superoxides and glutathione, using
      dichlorofluorescein diacetate (DCFH-DA), dihydroethidium (HET), and
      monochlorobimane (MCB), respectively. Effects on mitochondrial membrane potential
      were determined using 5,5',6,6'-tetrachloro-1,1',3,3'-
      tetraethylbenzimidazolylcarbocyanine iodide (JC-1). The ability of 17beta
      estradiol to prevent reactive oxygen species (ROS)-production in HLECs after
      exposure to 25 uM H2O2 for 24h was also measured. RESULTS: This study
      demonstrates increased mitotic activity in HLECs exposed to physiologic
      concentrations of 17beta-estradiol (1 nM). Pharmacological concentrations of
      17beta-estradiol caused increased number of apoptotic cell nuclei and caspase-3
      activation. Physiologic concentrations of 17beta-estradiol (0.1-10 nM) stabilized
      the mitochondrial membrane potential. Similar or slightly higher concentrations
      of 17beta-estradiol (0.01-1 uM) protected against H2O2-induced oxidative stress
      as evident by decreased levels of peroxides and superoxides. CONCLUSIONS: The
      present study demonstrates mitogenic and anti-oxidative effects of 17beta
      estradiol at physiologic concentrations, whereas pharmacological levels induced
      oxidative stress and acted pro-apoptotic in cultured lens cells.

PMID- 21850174
TI  - Infantile esotropia could be oligogenic and allelic with Duane retraction
      syndrome.
AB  - PURPOSE: To describe phenotyping and linkage analysis results for available
      members from a consanguineous nuclear family with hereditary congenital
      strabismus. METHODS: Both parents and all 12 children underwent clinical
      examination. Available affected and several unaffected family members had venous
      blood sampling for DNA extraction and 10K single nucleotide polymorphism (SNP)
      genotyping (Affymetrix Gene Chip(r) Human). Multipoint logarithm of the odds
      (LOD) score calculations were performed assuming an autosomal recessive mode of
      inheritance with 100% penetrance and disease allele frequency of 0.01%. RESULTS:
      Three children had non-syndromic large-angle infantile esotropia without
      significant hyperopia. A fourth child had left esotropic Duane retraction
      syndrome. A fifth child who had esotropia in the setting of prematurity and
      childhood poliomyelitis was excluded from the analysis. A sixth child had
      keratoconus and was excluded. Both parents and the remaining 6 children had no
      significant orthoptic or ophthalmic findings. Using linkage analysis including
      the 4 esotropic children, disease loci were mapped to regions on chromosomes
      3p26.3-26.2 and 6q24.2-25.1 using multipoint linkage analysis with LOD scores of
      3.18 and 3.25 respectively. Linkage to these regions persisted when the esotropic
      Duane retraction syndrome patient was excluded from the linkage analysis (LOD
      scores of 2.00 and 2.32, respectively). CONCLUSIONS: Non-syndromic infantile
      esotropia could be related to susceptibility loci on chromosomal regions 3p26.3
      26.2 and 6q24.2-25.1 and may share alleles that underlie Duane retraction
      syndrome.

PMID- 21850175
TI  - Intraocular and serum cytokine profiles in patients with intermediate uveitis.
AB  - PURPOSE: To study the intraocular and serum cytokine and chemokine profile in
      patients with intermediate uveitis (IU) at various stages of inflammatory
      activity. METHODS: Institutional, prospective association study. Paired aqueous
      humor (AqH) and serum samples were collected from 36 consecutive IU patients and
      10 controls. The concentrations of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL
      12p70, tumor necrosis factor (TNF)-alpha, CC--chemokine ligand 5/regulated upon
      activation normal T-cell expressed, and secreted (CCL5/RANTES), CC--chemokine
      ligand 3/macrophage inflammatory protein 1alpha (CCL3/MIP-1alpha), CCL4/MIP
      1beta, and CC--chemokine ligand 2/monocyte chemotactic protein--1 (CCL2/MCP-1)
      were measured in both AqH and serum by multiplex immunoassay. Main outcome
      measures were serum and intraocular levels of the analyzed cyto- and chemokines.
      RESULTS: Patients with IU had higher serum levels of TNF-alpha than non-uveitic
      controls (p<0.0001), whereas their AqH TNF-alpha levels did not show a difference
      (p=0.323). IU patients had higher intraocular levels of IL-1beta, IL-6, IL-8, IL
      10, IL-12p70 and CCL2/MCP-1 than the controls (p=0.020, 0.001, <0.0001, 0.005,
      0.003, and 0.003, respectively). Active stages of IU were characterized by higher
      levels of IL-6, IL-8, CCL5/RANTES and CCL2/MCP-1 (p=0.003, <0.0001, 0.033, and
      0.033, respectively). Higher levels of IL-6 and IL-8 were found in IU patients
      with cystoid macular edema (CME) compared to non-CME IU patients (p=0.026 and
      0.012, respectively). Significant positive correlations between various observed
      mediators were present in the AqH of IU patients only. CONCLUSIONS: Significantly
      elevated concentrations of multiple intraocular cytokines were found in IU
      patients, especially IL-6 and IL-8 in those with CME and active disease. In serum
      elevated TNF-alpha levels were observed in IU patients. Our findings improve the
      understanding of the pathogenesis of IU and contribute to the identification of
      factors which may contribute to the activity of IU.

PMID- 21850176
TI  - ZBED4, a cone and Muller cell protein in human retina, has a different cellular
      expression in mouse.
AB  - PURPOSE: ZBED4, a protein in cones and Muller cells of human retina, may play
      important functions as a transcriptional activator of genes expressed in those
      cells or as a co-activator/repressor of their nuclear hormone receptors. To begin
      investigating these potential roles of ZBED4, we studied the developmental
      expression and localization of both the Zbed4 mRNA and protein of mouse retina.
      METHODS: northern blots showed the presence of Zbed4 mRNA in retina and other
      mouse tissues, and western blots showed the nuclear and cytoplasmic expression of
      Zbed4 at different developmental times. Antibodies against Zbed4 and specific
      retinal cell markers were used for retinal immunohistochemistry. RESULTS: Zbed4
      mRNA was present at different levels in all the mouse tissues analyzed. The Zbed4
      protein was barely detectable at embryonic day (E)14.5 but was clearly seen at
      E16 at both retinal outer and vitreal borders and throughout the retina by E18
      and postnatal day 0 (P0). Thereafter, Zbed4 expression was more restricted to the
      inner retina. While ZBED4 is localized in cones and endfeet of Muller cells of
      human retina, in adult mouse retina Zbed4 is only detected in Muller cell endfeet
      and processes. The same localization of Zbed4 was observed in rat retina. In
      early development, Zbed4 is mainly present in the nuclear fraction of the mouse
      retina, and in adulthood it becomes more enriched in the cytoplasmic fraction.
      CONCLUSIONS: The patterns of spatial and temporal expression of Zbed4 in the
      mouse retina suggest a possible involvement of this protein in retinal
      morphogenesis and Muller cell function.

PMID- 21850177
TI  - Selenium effectively inhibits 1,2-dihydroxynaphthalene-induced apoptosis in human
      lens epithelial cells through activation of PI3-K/Akt pathway.
AB  - PURPOSE: To investigate whether activation of the phosphatidylinositol 3-kinase
      (PI3-K)/protein kinase B (Akt) pathway was necessary for selenium in protecting
      human lens epithelial cells (hLECs) from 1,2-dihydroxynaphthalene (1,2-DHN)
      induced apoptosis. In addition, we studied the link between heat shock protein 70
      (HSP70) expression and Akt phosphorylation in selenium-induced cell protection.
      METHODS: Cell viabilities were assessed by Cell Counting Kit-8 (CCK-8) kit and
      trypan blue exclusion. The effect of sodium selenite on Akt phosphorylation was
      studied. After the pretreatment with 30 MUM of LY294002, a PI3-K/Akt pathway
      inhibitor, apoptosis was assessed by flow cytometry, protein levels of phospho
      Akt and Akt were quantified by western blot, and cell localization of phospho-Akt
      was determined by immunofluorescence staining. Time-course effect of sodium
      selenite on HSP70 expression was studied by reverse transcription polymerase
      chain reaction (RT-PCR) and western blot. Moreover, effect of LY294002 on HSP70
      expression was also examined. RESULTS: Our data showed that sodium selenite
      increased cell viabilities and prevented 1,2-DHN-induced apoptosis through
      phosphorylation and nuclear translocation of Akt. Furthermore, pretreatment of
      LY294002 inhibited the phosphorylation of Akt. However, it failed to block the
      selenium-induced upregulation of HSP70. CONCLUSIONS: The activation of PI3-K/Akt
      pathway was necessary for selenium in protecting hLECs from 1,2-DHN-induced
      apoptosis. However, this pathway was not involved in the selenium-induced
      upregulation of HSP70.

PMID- 21850178
TI  - Identification of novel suggestive loci for high-grade myopia in Polish families.
AB  - PURPOSE: Myopia is the most common human eye disorder with complex genetic and
      environmental causes. To date, several myopia loci have been identified in
      families of different geographic origin. However, no causative gene(s) have yet
      been identified. The aim of this study was the characterization of Polish
      families with high-grade myopia, including genetic analysis. METHODS: Forty-two
      multiplex Polish families with non-syndromic high-grade myopia participated in
      the study. All family members underwent detailed ophthalmic examination and high
      grade myopia was defined as <=-6.0 diopters (D) based on the spherical refractive
      error. A genome-wide single nucleotide polymorphism (SNP)-based high-density
      linkage scan was performed using Affymetrix Human SNP Array 6.0 on a selected
      family (HM-32) with multiple affected individuals. RESULTS: Nonparametric linkage
      analysis identified three novel loci in family HM-32 at chromosome 7p22.1-7p21.1
      ([NPL] 8.26; p=0.006), chromosome 7p12.3-7p11.2 ([NPL] 8.23; p=0.006), and
      chromosome 12p12.3-12p12.1 ([NPL] 8.02; p=0.006), respectively. The effect of
      linkage disequilibrium on linkage due to dense SNP map was addressed by
      systematically pruning SNPs from the linkage panel. CONCLUSIONS: Haplotype
      analysis with informative crossovers in affected individuals defined a 12.2;
      10.9; and 9.5 Mb genomic regions for high-grade myopia spanned between SNP
      markers rs11977885/rs10950639, rs11770622/rs9719399, and rs4763417/rs10842388 on
      chromosomes 7p22.1-7p21.1, 7p12.3-7p11.2, and 12p12.3-12p12.1, respectively.

PMID- 21850179
TI  - Protective effect of canolol from oxidative stress-induced cell damage in ARPE-19
      cells via an ERK mediated antioxidative pathway.
AB  - PURPOSE: Oxidative stress damage to retinal pigment epithelial (RPE) cells is
      thought to play a critical role in the pathogenesis of age-related macular
      degeneration (AMD). This study was conducted to investigate the protective effect
      of canolol against oxidative stress-induced cell death in ARPE-19 cells and its
      underlying mechanism. METHODS: ARPE-19 cells, a human retinal pigment epithelial
      cell line, were subjected to oxidative stress with 150 MUM t-butyl hydroxide (t
      BH) in the presence/absence of canolol in different concentrations. Cell
      viabilities were monitored by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl
      tetrazolium bromide (MTT) assay. The apoptosis was measured by flow cytometry
      using Annexin V-FITC and PI staining and intracellular reactive oxygen species
      (ROS) levels were measured by a fluorescence spectrophotometer. Gene expression
      of NF-E2-related factor (Nrf-2), heme oxygenase-1 (HO-1), catalase and
      glutathione S-transferase-pi (GST-pi) were measured by a reverse transcription
      polymerase chain reaction (RT-PCR) assay. Activation of the extracellular signal
      regulated kinase (ERK) protein was evaluated by western blot analysis. RESULTS:
      Canolol showed relatively high safety for ARPE-19 cells and recovered the cell
      death caused by t-BH dose-dependently at a concentration of 50-200 MUM. Canolol
      also reduced t-BH-induced intracellular ROS generation and thus protected ARPE-19
      cells from cell apoptosis. HO-1, catalase, GST-pi, and Nrf-2 were elevated in
      ARPE-19 cells after treatment with different concentrations of canolol for 24 h.
      Finally, canolol was found to activate extracellular signal regulated kinase
      (ERK) phosphorylation in ARPE-19 cells under the condition, with or without t-BH.
      CONCLUSIONS: Canolol protected ARPE-19 cells from t-BH-induced oxidative damage
      and the protective mechanism was associated, at least partly, with the
      upregulation (activation) of antioxidative enzymes, probably through an ERK
      mediated pathway. This suggests that canolol offers a remarkable protective
      effect against oxidative damage of RPE cells and may have a therapeutic effect on
      AMD and other oxidative stress-related retinal diseases.

PMID- 21850180
TI  - Cerulean cataract mapped to 12q13 and associated with a novel initiation codon
      mutation in MIP.
AB  - PURPOSE: To identify the genetic defect in a large Chinese family with autosomal
      dominant cerulean cataract. METHODS: Genomic DNA and clinical data were collected
      from the family. Candidate gene sequencing and genome-wide linkage analysis were
      used to disclose the molecular basis responsible for cerulean cataract in the
      family. RESULTS: Initially, sequencing analysis of the three genes (beta-B2
      crystallin [CRYBB2], gamma-D-crystallin [CRYGD], and V-MAF avian
      musculoaponeurotic fibrosarcoma oncogene homolog [MAF]) known to cause cerulean
      cataract failed to find any mutation. Then, genome-wide linkage analysis mapped
      the disease to chromosome 12q13-q22 between D12S85 and D12S351, with a maximum
      lod score of 4.10 at theta=0. Sequence analysis of the major intrinsic protein of
      lens fiber gene (MIP), a gene known to cause other types of cataract in the
      linkage interval, detected a novel heterozygous initiation codon mutation, c.2T>C
      (p.Met1?). This mutation was present in all patients with cerulean cataract but
      was not present in any of the 13 unaffected family members nor in 96 control
      individuals. CONCLUSIONS: Cerulean cataract was found in a large family and is
      caused by a novel initiation codon mutation in MIP. This study adds a new member
      in the existing list of genes causing cerulean cataract and expands the mutation
      spectrum and phenotypic association of MIP mutations.

PMID- 21850181
TI  - Glycyrrhizin could reduce ocular hypertension induced by triamcinolone acetonide
      in rabbits.
AB  - PURPOSE: To evaluate the hypotensive effects of glycyrrhizin (GL) on a rabbit
      model of ocular hypertension (OH) induced by triamcinolone acetonide (TA).
      METHODS: Forty New Zealand White Rabbits were divided as follows: control
      (intravitreal injection of sterile saline solution); GL (intravitreal injection
      of sterile saline solution, then fed with 25mg GL/day); TA (intravitreal TA
      injection); TA+GL (intravitreal TA injection, then fed with GL) and GL+TA (pre
      treated with GL for 3 days, then got TA injection and the following GL
      treatment). Intraocular pressure (IOP), flash electroretinogram (flash ERG) and
      flash visual evoked potential (flash VEP) were measured during the follow-up (28
      days). The aqueous humor was analyzed, using (1)H-nuclear magnetic resonance
      spectroscopy and principal components analysis (PCA). RESULTS: IOP elevation was
      observed in the TA group during the follow-up, compared to the controls (p<0.01).
      The IOP was decreased in the TA+GL group and the GL+TA group, compared to the TA
      group (p<0.05). Both in flash ERG and VEP, the amplitudes were decreased, and the
      implicit time was prolonged in the TA group, compared to the controls (p<0.05);
      and the parameters were improved after intervention of GL, compared to the TA
      group (p<0.05). PCA results indicated that TA could affect ocular metabolism
      (especially the sugar metabolism), and GL could inhibit it. CONCLUSIONS: The
      administration of GL could suppress OH induced by TA in rabbits, and improve
      their electrophysiological parameters. Metabolomics is a useful tool in
      ophthalmology research. Our results indicate that TA-induced ocular metabolism
      changes could be compensated by GL.

PMID- 21850182
TI  - A G->T splice site mutation of CRYBA1/A3 associated with autosomal dominant
      suture cataracts in a Chinese family.
AB  - PURPOSE: To identify the genetic defect in a five-generation Chinese family with
      congenital Y-suture cataracts. METHODS: A five-generation Chinese family with
      inherited Y-suture cataract phenotype was recruited. Detailed family history and
      clinical data of the family were recorded. Candidate genes sequencing was
      performed to screen out the disease-causing mutation. RESULTS: The congenital
      cataract phenotype of the family was identified as Y-suture cataract type by
      using slit-lamp photography. Direct sequencing revealed a G->T splice site
      mutation in crystallin, beta A1 (CRYBA1/A3).This mutation co-segregated with all
      affected individuals in the family and was not found in unaffected family members
      or 100 unrelated controls. CONCLUSIONS: Our study identified a novel type of a
      splice site mutation in CRYBA1/A3 .The mutation was responsible for the
      congenital Y-suture cataracts in the family. This is the first report relating a
      G->T mutation of CRYBA1/A3 to congenital Y-suture cataract.

PMID- 21850183
TI  - Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial
      occurrence and potential implication of CYP26A1 and CYP26C1 genes.
AB  - PURPOSE: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or
      bilateral condition that leads to blindness in the affected eye, and is usually
      associated with other ocular abnormalities. Although bilateral ONA often occurs
      in association with severe congenital anomalies of the brain, nonsyndromic
      sporadic forms with bilateral ONA have been described. So far, no autosomal
      dominant nonsyndromic ONA has been reported. The genetic basis of this condition
      remains largely unknown, as no developmental genes other than paired box gene 6
      (PAX6) are known to be implicated in sporadic bilateral ONA. METHODS: The
      individuals reported underwent extensive ophthalmological, endocrinological, and
      neurologic evaluation, including neuroimaging of the visual pathways. In addition
      genomewide copy number screening was performed. RESULTS: Here we report an
      autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with
      unilateral microphthalmia and ONA in the second generation (II:1), and bilateral
      ONA in two sibs of the third generation (III:1; III:2). No PAX6 mutation was
      found. Genome wide copy number screening revealed a microdeletion of maximal 363
      kb of chromosome 10q23.33q23.33 in all affected individuals (II:1, III:1; III:2)
      and in unaffected I:1, containing three genes: exocyst complex component 6
      (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and
      cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode
      retinoic acid-degrading enzymes. CONCLUSIONS: This is the first study reporting
      an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of
      neuroimaging in uncovering ONA in microphthalmic patients is demonstrated.
      Although involvement of other genetic factors cannot be ruled out, our study
      might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic
      ONA.

PMID- 21850184
TI  - Copy number variation in the complement factor H-related genes and age-related
      macular degeneration.
AB  - PURPOSE: To determine the contribution of copy number variation (CNV) in the
      regulation of complement activation (RCA) locus to the development of age-related
      macular degeneration (AMD). METHODS: A multiplex ligation-dependent probe
      amplification assay was developed to quantify the number of copies of CFH, CFHR3,
      CFHR1, CFHR4, CFHR2, and CFHR5 in humans. Subjects with (451) and without (362)
      AMD were genotyped using the assay, and the impact on AMD risk was evaluated.
      RESULTS: Eight unique combinations of copy number variation were observed in the
      813 subjects. Combined deletion of CFHR3 and CFHR1 was protective (OR=0.47, 95%
      confidence interval 0.36-0.62) against AMD and was observed in 88 (82 [18.6%]
      with one deletion, 6 [1.4%] with two deletions) subjects with AMD and 127 (108
      [30.7%] with one deletion, 19 [5.4%] with two deletions) subjects without AMD.
      Other deletions were much less common: CFH intron 1 (n=2), CFH exon 18 (n=2),
      combined CFH exon 18 and CFHR3 (n=1), CFHR3 (n=2), CFHR1 (n=1), combined CFHR1
      and CFHR4 (n=15), and CFHR2 deletion (n=7, 0.9%). The combined CFHR3 and CFHR1
      deletion was observed on a common protective haplotype, while the others appeared
      to have arisen on multiple different haplotypes. CONCLUSIONS: We found copy
      number variations of CFHR3, CFHR1, CFHR4, and CFHR2. Combined deletion of CFHR3
      and CFHR1 was associated with a decreased risk of developing AMD. Other deletions
      were not sufficiently common to have a statistically detectable impact on the
      risk of AMD, and duplications were not observed.

PMID- 21850185
TI  - Mutation spectrum of CYP1B1 and MYOC genes in Korean patients with primary
      congenital glaucoma.
AB  - PURPOSE: To elucidate the incidence of cytochrome P450 1B1 (CYP1B1) and myocillin
      (MYOC) mutations in Korean patients with primary congenital glaucoma (PCG).
      METHODS: Genomic DNA was collected from peripheral blood of 85 unrelated Korean
      patients who were diagnosed as having PCG by standard ophthalmological
      examinations and screened for mutations in the CYP1B1 and MYOC genes by using bi
      directional sequencing. RESULTS: Among 85 patients with PCG, 22 patients (22/85;
      25.9%) had either one (n=11) or two (n=11) mutant alleles of the CYP1B1 gene.
      Among 11 different CYP1B1 mutations identified, a frameshift mutation
      (c.970_971dupAT; p.T325SfsX104) was the most frequent mutant allele (6/33; 18.2%)
      while p.G329S and p.V419Gfs11X were novel. In the MYOC gene, two variants of
      unknown significance (p.L228S and p.E240G) were identified in two PCG patients
      (2/85; 2.4%), respectively. No patient had mutations in both genes. CONCLUSIONS:
      Although CYP1B1 mutations are major causes of PCG in Korea, ~70% of PCG patients
      have neither CYP1B1 nor MYOC mutations suggesting a high degree of genetic
      heterogeneity. Furthermore, the fact that 11 out of 22 patients had only one
      mutant allele in the CYP1B1 gene necessitates further investigation for other
      genetic backgrounds underlying PCG.

PMID- 21850186
TI  - A comparison of stem cell-related gene expression in the progenitor-rich limbal
      epithelium and the differentiating central corneal epithelium.
AB  - PURPOSE: Corneal epithelium is maintained by a population of stem cells (SCs)
      that have not been identified by specific molecular markers. The objective of
      this study was to find new putative markers for these SCs and to identify
      associated molecular pathways. METHODS: Real time PCR (rt-PCR) was performed in
      24 human limbal and central corneal epithelial samples to evaluate the gene
      expression profile of known corneal epithelial SC-associated markers. A pool of
      those samples was further analyzed by a rt-PCR array (RT2-PCR-A) for 84 genes
      related to the identification, growth, maintenance, and differentiation of SCs.
      RESULTS: Cells from the corneal epithelium SC niche showed significant expression
      of ATP-binding cassette sub-family G member 2 (ABCG2) and cytokeratin (KRT)15,
      KRT14, and KRT5 genes. RT2-PCR-A results indicated an increased or decreased
      expression in 21 and 24 genes, respectively, in cells from the corneal SC niche
      compared to cells from the central corneal epithelium. Functional analysis by
      proprietary software found 4 different associated pathways and a novel network
      with the highest upregulated genes in the corneal SC niche. This led to the
      identification of specific molecules, chemokine (C-X-C motif) ligand 12 (CXCL12),
      islet-1 transcription factor LIM/homeodomain (ISL1), collagen-type II alpha 1
      (COL2A), neural cell adhesion molecule 1 (NCAM1), aggrecan (ACAN), forkhead box
      A2 (FOXA2), Gap junction protein beta 1/connexin 32 (GJB1/Cnx32), and Msh
      homeobox 1 (MSX1), that could be used to recognize putative corneal epithelial
      SCs grown in culture and intended for transplantation. Other molecules, NCAM1 and
      GJB1/Cnx32, potentially could be used to positively purify them, and Par-6
      partitioning defective 6 homolog alpha (PARD6A) to negatively purify them.
      CONCLUSIONS: Knowledge of these gene and molecular pathways has provided a better
      understanding of the signaling molecular pathways associated with progenitor-rich
      limbal epithelium. This knowledge potentially could give support to the design
      and development of innovative therapies with the potential to reverse corneal
      blindness arising from ocular surface failure.

PMID- 21850187
TI  - Pediatric cataract, myopic astigmatism, familial exudative vitreoretinopathy and
      primary open-angle glaucoma co-segregating in a family.
AB  - PURPOSE: To describe an Australian pedigree of European descent with a variable
      autosomal dominant phenotype of: pediatric cortical cataract (CC), asymmetric
      myopia with astigmatism, familial exudative vitreoretinopathy (FEVR), and primary
      open-angle glaucoma (POAG). METHODS: Probands with CC, FEVR, and POAG were
      enrolled in three independent genetic eye studies in Tasmania. Genealogy
      confirmed these individuals were closely related and subsequent examination
      revealed 11 other family members with some or all of the associated disorders.
      RESULTS: Twelve individuals had CC thought to be of childhood onset, with one
      child demonstrating progressive lenticular opacification. One individual had
      severe retinal detachment while five others had dragged retinal vessels. Seven
      individuals had POAG. Seven individuals had myopia in at least one eye <=-3
      Diopters. DNA testing excluded mutations in myocilin, trabecular meshwork
      inducible glucocorticoid response (MYOC) and tetraspanin 12 (TSPAN12). Haplotype
      analysis excluded frizzled family receptor 4 (FZD4) and low density lipoprotein
      receptor-related protein 5 (LRP5), but only partly excluded EVR3. Multipoint
      linkage analysis revealed multiple chromosomal single-nucleotide polymorphisms
      (SNPs) of interest, but no statistically significant focal localization.
      CONCLUSIONS: This unusual clustering of ophthalmic diseases suggests a possible
      single genetic cause for an apparently new cataract syndrome. This family's
      clinical ocular features may reflect the interplay between retinal disease with
      lenticular changes and axial length in the development of myopia and glaucoma.

PMID- 21850189
TI  - Mutation spectrum of PAX6 in Chinese patients with aniridia.
AB  - PURPOSE: To identify mutations in the paired box 6 (PAX6) gene of 33 probands
      with aniridia and to reveal the mutational spectrum in the Chinese population.
      METHODS: Unrelated probands with aniridia from 27 newly selected families and six
      previously analyzed families participated in this study. The coding regions of
      PAX6 in the 27 new families were analyzed using cycle sequencing. Families that
      lacked detectable variations based on sequencing (14 new and six previously
      analyzed) were further analyzed using multiplex ligation-dependent probe
      amplification (MLPA). RESULTS: Fifteen mutations were identified in 16 of the 33
      families: c.[65_94del30; 99_105dup7], c.101_102insA, c.177delG, c.238_239insGCGA,
      c.1033-42_1033-26del17insG, c.1A>G, c.120C>A, c.718C>T, c.949C>T, c.1062C>A,
      c.1183G>A, c.1268A>T, and three gross deletions involving exons 1-14, exons 8-14,
      and exons 9-14. The first five mutations were novel and the c.1268A>T mutation
      was present in two families. Phenotypic variations were observed between families
      and between different affected patients within the families. CONCLUSIONS: The
      PAX6 mutation spectrum in Chinese aniridia patients is comparable to that
      reported in other ethnic groups. Further studies of the 17 families with no
      detected mutations may provide additional information to improve the
      understanding of the molecular genetics of aniridia.

PMID- 21850188
TI  - Critical role of SDF-1alpha-induced progenitor cell recruitment and macrophage
      VEGF production in the experimental corneal neovascularization.
AB  - PURPOSE: To address the roles of the stromal derived factor-1 (SDF-1) alpha in
      the course of experimental corneal neovascularization (CNV). METHODS: CNV was
      induced by alkali injury and compared in SDF-1alpha- or vehicle-treated mice two
      weeks after injury. Angiogenic factor expression in the early phase after injury
      was quantified by reverse transcription polymerase chain reaction (RT-PCR).
      Progenitor cell, macrophage, and monocyte intracorneal accumulation in the early
      phase after injury was evaluated by flow cytometric analysis. RESULTS: The mRNA
      expression of SDF-1alpha was augmented, together with infiltration of c-kit
      positive progenitor cells in the corneas after the alkali injury. Compared with
      vehicle-treated mice, SDF-1alpha-treated mice exhibited enhanced CNV two weeks
      after injury, as evidenced by enlarged cluster of differentiation 31 (CD31)
      positive areas. Concomitantly, the intracorneal infiltration of c-kit-positive
      progenitor cells but not F4/80+ macrophages or Ly-6G+ monocytes was significantly
      enhanced in SDF-1alpha-treated mice compared to vehicle-treated mice. SDF-1alpha
      enhanced vascular endothelial growth factor (VEGF) expression by murine
      peritoneal macrophages. Enhancement in intraocular VEGF expression was greater in
      SDF-1alpha-treated mice than in control mice after injury. Moreover, local
      administration of C-X-C chemokine receptor type 4 (CXCR4) antagonist after alkali
      injury reduced alkali-induced CNV. CONCLUSIONS: SDF-1alpha-treated mice exhibited
      enhanced alkali-induced CNV through enhanced intracorneal progenitor cell
      infiltration and increased VEGF expression by macrophages.

PMID- 21850190
TI  - Neutralization of mouse interleukin-17 bioactivity inhibits corneal allograft
      rejection.
AB  - PURPOSE: To investigate the inhibitory effects of anti-mouse interleukin-17 (IL
      17) monoclonal antibody (mAb) in high-responder corneal allograft rejection.
      METHODS: C57BL/6 or BALB/c mice corneal grafts were grafted onto BALB/c hosts.
      The neutralizing mouse IL-17 antibody and isotype control were injected
      intraperitoneally immediately after transplantation for experimental treatment.
      At appropriate times after treatment, recipient grafts were assessed clinically
      and histologically, and recipient corneal graft- infiltrating cells were detected
      by immunohistochemistry and quantified by real-time PCR. The cytokine spleen
      levels of T helper type 1 (Th1), Th2, and Th17 were analyzed by enzyme-linked
      immunosorbent assay. Flow cytometric analysis was used to evaluate the
      frequencies of IL-17-producing Th17 cells. RESULTS: Neutralization of IL-17 with
      anti-IL-17 mAb obviously prolonged allograft survival compared to the group that
      received isotype control. Neovascularizations and inflammatory immune cells in
      corneal stroma decreased in the allogeneic recipients treated with anti-IL-17
      mAb. The mRNA (mRNA) level of graft-infiltrating cells, including neutrophiles,
      cluster of differentiation 4 (CD4) T cells, and CD8 T cells, decreased
      dramatically in the IL-17 neutralization group. At days 14 and 42, splenocytes
      from recipients treated with anti-IL-17 mAb produced significantly less of the
      pro-inflammatory cytokines interferon-gamma (IFN-gamma), IL-12p40, and IL-17
      compared to those from control Ig-treated recipients at day 14. However, Th2
      cytokine IL-4 and IL-5 production increased, and IL-13 levels were not
      significantly different among the three groups. IL-6 production was elevated in
      recipients treated with anti-IL-17 mAb. Anti-IL-17 mAb reduced the percentage of
      Th17 in CD4+ T cells, but there was no statistical significance between anti-IL
      17 mAb and the control group. CONCLUSIONS: Neutralization of mouse IL-17
      bioactivity with anti-IL-17 mAb improves allogeneic corneal graft survival and
      inhibits corneal allograft rejection to a certain extent by inhibiting production
      of graft-infiltrating inflammatory cells and decreasing the secretion of pro
      inflammatory cytokines.

PMID- 21850192
TI  - Susceptibility to primary angle closure glaucoma in Saudi Arabia: the possible
      role of mitochondrial DNA ancestry informative haplogroups.
AB  - PURPOSE: In a previous preliminary analysis we reported that mitochondrial DNA
      (mtDNA) haplogroup R0a was significantly more frequent in primary angle closure
      glaucoma (PACG) Saudi patients than in healthy Saudi controls. This result
      prompted us to extend our work using a significant larger Saudi PACG cohort and
      more healthy controls. METHODS: We sequenced the mtDNA regulatory hypervariable
      region-I (HVS-I) and coding regions, comprising haplogroup diagnostic
      polymorphisms, in 227 PACG Saudi patients and compared their haplogroup
      frequencies with those obtained from 186 matched healthy controls (free of PACG
      by examination) and from a large sample of 810 healthy Saudi Arabs representing
      the general Saudi population. RESULTS: MtDNA Haplogroups R0a and J, the most
      abundant lineages in Saudi Arabia, were in significant higher frequencies in the
      PACG patients than in controls, while the widespread western Eurasian haplogroup
      U was associated with reduced risk to developing PACG. CONCLUSIONS: Haplogroups
      R0a and J could be ancestry informative markers for PACG in the Saudi Arabian
      population. In addition, the western Eurasian haplogroup U may play a mild
      protective effect to this illness.

PMID- 21850191
TI  - Development of spontaneous neuropathy in NF-kappaBp50-deficient mice by
      calcineurin-signal involving impaired NF-kappaB activation.
AB  - PURPOSE: The transcriptional regulator, nuclear factor-kappa B (NF-kappaB)/Rel
      family are involved in neuronal cell death and survival. Previously, we reported
      that NF-kappaBp50-deficient (p50-deficient) mice exhibit many features resembling
      human normal tension glaucoma (NTG). The developmental mechanism of human NTG is
      not clearly understood, and a radical curative treatment has yet to be
      established. Our aim is to elucidate the signal cascade which mediates the
      spontaneous optic neuropathy in p50-deficient mice as a model of NTG. METHODS: To
      demonstrate the expression and activation of pro-apoptotic factors, which mediate
      the death of retinal ganglion cells (RGCs) in p50-deficient mice, western blot
      (WB) and luciferase reporter assays with retinas from p50-deficient and wild type
      mice, and cultured RGC-5 cells were performed. Furthermore, we tested the
      neuroprotective effects of chemical reagents (memantine, lomerizine, and
      tacrolimus) against N-methyl-D-aspartate (NMDA)-susceptible RGC damage according
      to in vitro experiments with RGC-5 cells. To elucidate the NF-kappaB-mediated
      death signaling, the effects of chemical reagents on spontaneous optic neuropathy
      were examined by histopathological studies. RESULTS: WB experiments and
      luciferase reporter assays showed that NF-kappaB-inducible BCL2-associated X
      protein (Bax) and a pro-apoptotic factor, activated caspase 3 were expressed in
      the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Further,
      the constitutively active cleaved forms of calcineurin (CaN), which have been
      reported to lead to apoptosis, were detected in the retina of p50-deficient mice
      as well as NMDA-treated RGC-5 cells. Pre-treatment with tacrolimus markedly
      protected RGC-5 cells from NMDA-induced neurotoxicity, and then both spontaneous
      RGC death and degenerative changes to the optic nerve in p50-deficient mice were
      significantly reduced by the chronic administration of tacrolimus. The
      experiments with cultured RGC-5 cells supported the results of histological
      examinations with p50-deficient mice, suggesting that CaN activation leads to NF
      kappaB-induced Bax activation and caspase 3 activation, and mediates spontaneous
      optic neuropathy in p50-deficient mice. CONCLUSIONS: Research findings show that
      the chronic administration of tacrolimus significantly reduces spontaneous optic
      neuropathy in p50-deficient mice. We demonstrated a potential CaN signal cascade,
      which spontaneously induces age-dependent RGC death and degenerative optic nerve
      changes in p50-deficient mice.

PMID- 21850194
TI  - Evaluation of the prevalence of concomitant idiopathic cyclic edema and
      cellulite.
AB  - The aim of this study was to evaluate the prevalence of concomitant idiopathic
      cyclic edema with Grade II and III cellulite. All patients treated for Grade II
      and III cellulite were evaluated for idiopathic cyclic edema in a retrospective,
      quantitative and cross-sectional study. The study was carried out at the Godoy
      Clinic in the period from 2006 to 2010. All patients with body mass indexes > 25,
      Grade I cellulite and other causes of edema were excluded. The diagnosis of
      idiopathic cyclic edema was based on a clinical history and fluid retention
      throughout the day, in particular difficulty in removing rings on waking in the
      morning which improves later in the day. All patients with cyclic edema were
      treated with 75 mg aminaphtone three times daily. Statistical analysis considered
      the frequency of edema. Of the 82 women evaluated with ages between 18 and 58
      years old (mean of 34.9 years) 41 (50.0%) were diagnosed with idiopathic cyclic
      edema. Idiopathic cyclic edema is an aggravating factor for cellulite and is
      frequently associated with the more advanced stages of the disease. Its control
      is essential in the treatment of cellulite.

PMID- 21850193
TI  - Effect of weight reduction on cardiovascular risk factors and CD34-positive cells
      in circulation.
AB  - Being overweight or obese is associated with an increased risk for the
      development of non-insulin-dependent diabetes mellitus, hypertension, and
      cardiovascular disease. Dyslipidemia of obesity is characterized by elevated
      fasting triglycerides and decreased high-density lipoprotein-cholesterol
      concentrations. Endothelial damage and dysfunction is considered to be a major
      underlying mechanism for the elevated cardiovascular risk associated with
      increased adiposity. Alterations in endothelial cells and stem/endothelial
      progenitor cell function associated with overweight and obesity predispose to
      atherosclerosis and thrombosis. In our study, we analyzed the effect of a low
      calorie diet in combination with oral supplementation by vitamins, minerals,
      probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body
      composition, lipid profile and CD34-positive cells in circulation. During this
      dieting program, the following parameters were assessed weekly for all
      participants: fat free mass, body fat, BMI, extracellular/intracellular water,
      total body water and basal metabolic rate. For part of participants blood
      chemistry parameters and circulating CD34-positive cells were determined before
      and after dieting. The data indicated that the treatments not only reduced body
      fat mass and total mass but also improved the lipid profile. The changes in body
      composition correlated with the level of lipoproteins responsible for the
      increased cardiovascular risk factors. These changes in body composition and
      lipid profile parameters coincided with the improvement of circulatory progenitor
      cell numbers. As the result of our study, we concluded that the improvement of
      body composition affects the number of stem/progenitor cells in circulation.

PMID- 21850196
TI  - Patient specification quality assurance for glioblastoma multiforme brain tumors
      treated with intensity modulated radiation therapy.
AB  - The aim of this study was to evaluate the significance of performing patient
      specification quality assurance for patients diagnosed with glioblastoma
      multiforme treated with intensity modulated radiation therapy. The study
      evaluated ten intensity modulated radiation therapy treatment plans using 10 MV
      beams, a total dose of 60 Gy (2 Gy/fraction, five fractions a week for a total of
      six weeks treatment). For the quality assurance protocol we used a two
      dimensional ionization-chamber array (2D-ARRAY). The results showed a very good
      agreement between the measured dose and the pretreatment planned dose. All the
      plans passed >95% gamma criterion with pixels within 5% dose difference and 3 mm
      distance to agreement. We concluded that using the 2D-ARRAY ion chamber for
      intensity modulated radiation therapy is an important step for intensity
      modulated radiation therapy treatment plans, and this study has shown that our
      treatment planning for intensity modulated radiation therapy is accurately done.

PMID- 21850195
TI  - Trace elements, heavy metals and vitamin levels in patients with coronary artery
      disease.
AB  - AIM: In the present study, we aimed to assess serum concentrations of zinc (Zn),
      copper (Cu), iron (Fe), cadmium (Cd), lead (Pb), manganese (Mn), vitamins A
      (retinol), D (cholecalciferol) and E (alpha-tocopherol) in patients with coronary
      artery disease (CAD) and to compare with healthy controls. METHODS: A total of 30
      CAD patients and 20 healthy subjects were included in this study. Atomic
      absorption spectrophotometry (UNICAM-929) was used to measure heavy metal and
      trace element concentrations. Serum alpha-tocopherol, retinol and cholecalciferol
      were measured simultaneously by high performance liquid chromatography (HPLC).
      RESULTS: Demographic and baseline clinical characteristics were not statistically
      different between the groups. Serum concentrations of retinol (0.3521 +/- 0.1319
      vs. 0.4313 +/- 0.0465 mmol/I, p=0.013), tocopherol (3.8630 +/- 1.3117 vs. 6.9124
      +/- 1.0577 mmol/I, p<0.001), cholecalciferol (0.0209 +/- 0.0089 vs. 0.0304+/
      0.0059 mmol/I, p<0.001) and Fe (0.5664 +/- 0.2360 vs. 1.0689 +/- 0,4452 ug/dI,
      p<0.001) were significantly lower in CAD patients. In addition, while not
      statistically significant serum Cu (1.0164 +/- 0.2672 vs. 1.1934 +/- 0.4164
      ug/dI, p=0.073) concentrations were tended to be lower in patients with CAD,
      whereas serum lead (0.1449 +/- 0.0886 vs. 0.1019 +/- 0.0644 ug/dI, p=0.069)
      concentrations tended to be higher. CONCLUSIONS: Serum level of trace elements
      and vitamins may be changed in patients with CAD. In this relatively small study
      we found that serum levels of retinol, tocopherol, cholecalciferol, iron and
      copper may be lower whereas serum lead concentrations may be increased in
      patients with CAD.

PMID- 21850197
TI  - Spontaneous hemoperitoneum caused by a diverticulum of the sigmoid colon.
AB  - The diverticulum of the sigmoid colon is relatively common in the
      gastrointestinal tract, with the majority of cases being asymptomatic. A non
      traumatic hemoperitoneum secondary to colonic diverticulum is very rare. Here, we
      report the case of a 35-year-old woman with hemoperitoneum caused by the bleeding
      of the serosal vessel of the sigmoid colon diverticulum. The bleeding focus was
      identified and ligated, and the diverticulum was invaginated laparoscopically. No
      blood vessel malformation was detected.

PMID- 21850198
TI  - The relationship between serum uric acid and spirometric values in participants
      in a health check: the Takahata study.
AB  - BACKGROUND: Tissue hypoxia induces the degradation of adenosine triphosphate,
      resulting in the production of uric acid (UA). Patients with chronic obstructive
      pulmonary disease (COPD) have been reported to have high serum levels of UA
      (sUA), compared with control subjects. However, the relationship between sUA
      levels and spirometric measures has not been investigated in detail in a general
      population. METHODS: Subjects aged 40 years or older (n = 2,917), who had
      participated in a community-based annual health check in Takahata, Japan, in 2004
      and 2005, were enrolled in the study. These subjects performed spirometry, their
      blood pressure was measured, and a blood sample was taken. RESULTS: sUA levels
      were significantly higher in males than in females. Percent predicted forced
      vital capacity [FVC %predicted] (r = -0.13) and forced expiratory volume in 1 s
      [FEV(1) %predicted] (r = -0.118) were inversely correlated with sUA levels in
      females but not in males. Univariate regression analysis indicated that age, body
      mass index (BMI), ethanol intake, mean blood pressure (BP), and serum creatinine
      (sCr) were significantly associated with sUA levels in males. In females, age,
      BMI, mean BP, hemoglobin A1c, sCr, FVC %predicted, and FEV(1) %predicted were
      significantly associated with sUA levels. Multiple linear regression analysis
      showed that for both genders, FVC %predicted and FEV(1) %predicted were
      predictive for sUA levels, independently of the other clinical parameters.
      Subjects with lung restriction had higher sUA levels than subjects without lung
      restriction. In addition, subjects with moderate and severe airflow limitation
      had higher sUA levels than subjects without airflow limitation or those with mild
      airflow limitation. CONCLUSION: FVC %predicted and FEV(1) %predicted were
      significantly associated with sUA levels in a general population.

PMID- 21850199
TI  - Spindle cell lipoma of the hypopharynx.
AB  - OBJECTIVE: We report a rare case of a spindle cell lipoma with atypical clinical
      course. CASE REPORT: A 51 year old female patient referred to our clinic with
      feeling of mass in the throat she had had for two years. The patient described
      difficulty in swallowing. Indirect laryngoscopy did not reveal any masses at
      bilateral pyriform sinuses, and the mucosa had a natural appearance. However, a
      mass with a stalk was detected in the side of the mouth when the patient retched.
      Endoscopic monitoring of the mass revealed its origin to be the left sinus
      pyriformis. No pathological structures could be detected in the indirect
      laryngoscopy taken after the patient gulped again. The mass was shown by magnetic
      resonance imaging to extend into the esophagus. It was removed using suspension
      microlaryngoscopy. Postoperative control revealed a complete healing at the
      excision site. Immunohistochemical examination for pathological diagnosis
      indicated a spindle cell lipoma. CONCLUSIONS: Laryngeal and hypopharyngeal
      lipomas are rare forms of benign laryngeal neoplasms. Their asymptomatic course
      makes diagnosis difficult. The patient is presented here with related clinical
      and pathological features.

PMID- 21850200
TI  - A voxel-based morphometric analysis of cerebral gray matter in subcortical
      ischemic vascular dementia patients and normal aged controls.
AB  - BACKGROUND AND PURPOSE: The present study was designed to detect the
      abnormalities of the cerebral grey-matter density in subcortical ischemic
      vascular dementia patients by FSL-VBM method to promote the early diagnosis of
      it. METHODS: Nine subcortical ischemic vascular dementia patients and nine age
      matched normal controls underwent MRI brain structure scanning that was performed
      on a SIEMENS AVANTO 1.5 Tesla scanner and standard T1-weighted high-resolution
      anatomic scans of MPRAGE sequence were obtained. The 3-demensional MPRAGE images
      were processed with FSL-VBM package and the cerebral gray matter density was
      compared between the subcortical ischemic vascular dementia patients and normal
      controls. RESULTS: Compared with the normal control group, the cerebral gray
      matter density of subcortical ischemic vascular dementia patients was found
      significantly decreasing, including brain regions of thalamus, parietal lobe,
      frontal lobe and temporal lobe (P<0.05). CONCLUSIONS: The cerebral gray matter
      density alterations have closed correlation with cognitive dysfunction in
      subcortical ischemic vascular dementia patient and can be detected by MRI. MRI
      has some potential value in the diagnosis of them.

PMID- 21850201
TI  - Transplantation with bone marrow stromal cells promotes wound healing under
      chemotherapy through altering phenotypes.
AB  - Stem cell transplantation is a promising strategy for delayed wound healing
      caused by chemotherapy. However, the fate of stem cells under chemotherapy has
      not been fully elucidated. Herein we characterized human fetal bone marrow
      stromal cells (hBMSCs) during wound healing in mice treated with cyclophosphamide
      (CTX). The isolated hBMSCs expressed the phenotype of
      CD11b(low)/CD14(low)/CD34(low)/CD45(low)/CD29(high)/CD44(high)/CD90(high)/CD105(h
      gh)/CD146(high)/STRO-1(low). Following in vitro exposure to CTX, hBMSCs showed
      decreased cell growth in a dose- and time-dependent manner, accompanied by
      increased expressions of collagen-I/III, and CD31. After transplantation, wounds
      closed as early as 8 days and were positive for alpha-smooth muscle actin (alpha
      SMA), implicating the enhanced re-epithelialization and wound contraction.
      Moreover, proliferating cell nuclear antigen (PCNA) and CD31 showed co
      localization with alpha-SMA, suggesting the differentiation of hBMSCs into
      epithelial cells and myofibroblasts/fibroblasts. Taken together, our results
      indicate hBMSCs can accelerate wound healing under chemotherapy through altering
      their phenotypes.

PMID- 21850202
TI  - Vitamin E modulates cigarette smoke extract-induced cell apoptosis in mouse
      embryonic cells.
AB  - Vitamin E (VE) can effectively prevent occurrence of lung cancer caused by
      passive smoking in mice. However, whether VE prevents smoking-induced
      cytotoxicity remains unclear. In this study, a primary culture of embryonic lung
      cells (ELCs) was used to observe the cytotoxic effects of cigarette smoke extract
      (CSE), including its influence on cell survival, cell cycle, apoptosis, and DNA
      damage, and also to examine the effects of VE intervention on CSE-induced
      cytotoxicity. Our results showed that CSE could significantly inhibit the
      survival of ELCs with dose- and time-dependent effects. Furthermore, CSE clearly
      disturbed the cell cycle of ELCs by decreasing the proportion of cells at the S
      and G2/M phases and increasing the proportion of cells at the G0/G1 phase. CSE
      promoted cell apoptosis, with the highest apoptosis rate reaching more than 40%.
      CSE also significantly caused DNA damage of ELCs. VE supplementation could
      evidently inhibit or reverse the cytotoxic effects of CSE in a dose- and time
      dependent manner. The mechanism of CSE effects on ELCs and that of VE
      intervention might involve the mitochondrial pathway of cytochrome c-mediated
      caspase activation. Our study validate that VE plays a clearly protective effect
      against CSE-induced cytotoxicity in mouse embryonic lung cells.

PMID- 21850203
TI  - Biological characteristics of foam cell formation in smooth muscle cells derived
      from bone marrow stem cells.
AB  - Bone marrow mesenchymal stem cells (BMSC) can differentiate into diverse cell
      types, including adipogenic, osteogenic, chondrogenic and myogenic lineages.
      There are lots of BMSC accumulated in atherosclerosis vessels and differentiate
      into VSMC. However, it is unclear whether VSMC originated from BMSC (BMSC-SMC)
      could remodel the vessel in new tunica intima or promote the pathogenesis of
      atherosclerosis. In this study, BMSC were differentiated into VSMC in response to
      the transforming growth factor beta (TGF-beta) and shown to express a number of
      VSMC markers, such as alpha-smooth muscle actin (alpha-SMA) and smooth muscle
      myosin heavy chain1 (SM-MHC1). BMSC-SMC became foam cells after treatment with 80
      mg/L ox-LDL for 72 hours. Ox-LDL could upregulate scavenger receptor class A (SR
      A) but downregulate the ATP-binding cassette transporter A1 (ABCA1) and caveolin
      1 protein expression, suggesting that modulating relative protein activity
      contributes to smooth muscle foam cell formation in BMSC-SMC. Furthermore, we
      found that BMSC-SMC have some biological characteristics that are similar to
      VSMC, such as the ability of proliferation and secretion of extracellular matrix,
      but, at the same time, retain some biological characteristics of BMSC, such as a
      high level of migration. These results suggest that BMSC-SMC could be induced to
      foam cells and be involved in the development of atherosclerosis.

PMID- 21850204
TI  - Molecular characterization of transcriptome-wide interactions between highly
      pathogenic porcine reproductive and respiratory syndrome virus and porcine
      alveolar macrophages in vivo.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) infects mainly the
      porcine alveolar macrophages (PAMs) and causes porcine reproductive and
      respiratory syndrome (PRRS). Previous studies have analyzed the global gene
      expression profiles of lung tissue in vivo and PAMs in vitro following infection
      with PRRSV, however, transcriptome-wide understanding of the interaction between
      highly pathogenic PRRSV (HP-PRRSV) and PAMs in vivo has not yet been established.
      In this study, we employed Affymetrix microarrays to investigate the gene
      expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous
      breed) after infection with HP-PRRSV. During the infection, Tongcheng piglets
      exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia,
      lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi.
      Microarray analysis revealed that HP-PRRSV infection has affected PAMs in
      expression of the important genes involved in cytoskeleton and exocytosis
      organization, protein degradation and folding, intracellular calcium and zinc
      homeostasis. Several potential antiviral strategies might be employed in PAMs,
      including upregulating IFN-induced genes and increasing intracellular zinc ion
      concentration. And inhibition of the complement system likely attenuated the lung
      damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could
      lead to a better understanding of the HP-PRRSV-host interaction, and to the
      identification of novel antiviral therapies and genetic components of swine
      tolerance/susceptibility to HP-PRRS.

PMID- 21850205
TI  - RNA granules present only in extracellular toxoplasma gondii increase parasite
      viability.
AB  - Toxoplasma gondii is an obligate intracellular parasite. When searching for a new
      cell to invade, the parasites have to confront the stress of being exposed to the
      extracellular environment. The mechanisms by which T. gondii survives outside the
      host cells are poorly understood. In this work we show that extracellular
      parasites form mRNA aggregates with characteristics of stress granules.
      Intracellular tachyzoites or bradyzoites do not form mRNA granules. We tested
      different stimuli that trigger granule formation in vitro and discovered that a
      buffer that mimics the host cell cytosol ionic composition (high potassium)
      strongly induces granule formation, suggesting that the granules arise when the
      parasites come in contact with the host cell cytosol during egress. We examined
      the importance of granule formation for parasite viability and show that the
      parasite populations that are able to form granules have a growth advantage,
      increased invasion, and decreased apoptosis in the extracellular environment.
      Overall, granule formation improves the fitness of extracellular parasites and
      increases the efficiency of the lytic cycle.

PMID- 21850206
TI  - In vitro evaluation of natural marine sponge collagen as a scaffold for bone
      tissue engineering.
AB  - The selection of a suitable scaffold matrix is critical for cell-based bone
      tissue engineering. This study aimed to identify and characterize natural marine
      sponges as potential bioscaffolds for osteogenesis. Callyspongiidae marine sponge
      samples were collected from the Fremantle coast of Western Australia. The sponge
      structure was assessed using scanning electron microscopy (SEM) and Hematoxylin
      and eosin. Mouse primary osteoblasts were seeded onto the sponge scaffold and
      immunostained with F-actin to assess cell attachment and aggregation. Alkaline
      phosphatase expression, von Kossa staining and real-time PCR were performed to
      examine the osteogenic potential of sponge samples. SEM revealed that the sponge
      skeleton possessed a collagenous fibrous network consisting of interconnecting
      channels and a porous structure that support cellular adhesion, aggregation and
      growth. The average pore size of the sponge skeleton was measured 100 to 300 MUm
      in diameter. F-actin staining demonstrated that osteoblasts were able to anchor
      onto the surface of collagen fibres. Alkaline phosphatase expression, a marker of
      early osteoblast differentiation, was evident at 7 days although expression
      decreased steadily with long term culture. Using von Kossa staining,
      mineralisation nodules were evident after 21 days. Gene expression of osteoblast
      markers, osteocalcin and osteopontin, was also observed at 7, 14 and 21 days of
      culture. Together, these results suggest that the natural marine sponge is
      promising as a new scaffold for use in bone tissue engineering.

PMID- 21850207
TI  - PTPBR7 binding proteins in myelinating neurons of the mouse brain.
AB  - Mouse protein tyrosine phosphatase PTPBR7 is a receptor-like, transmembrane
      protein that is localized on the surface of neuronal cells. Its protein
      phosphatase activity is reduced upon multimerization, and PTPBR7-deficient mice
      display motor coordination defects. Extracellular molecules that may influence
      PTPBR7 activity, however, remain to be determined. We here show that the PTPBR7
      extracellular domain binds to highly myelinated regions in mouse brain, in
      particular the white matter tracks in cerebellum. PTPBR7 deficiency does not
      alter this binding pattern, as witnessed by RAP in situ staining of Ptprr-/-
      mouse brain sections. Additional in situ and in vitro experiments also suggest
      that sugar moieties of heparan sulphate and chondroitin sulphate
      glycosaminoglycans are not critical for PTPBR7 binding. Candidate binding
      proteins were affinity-purified exploiting the PTPBR7 extracellular domain and
      identified by mass spectrometric means. Results support the suggested link
      between PTPRR isoforms and cerebellar calcium ion homeostasis, and suggest an
      additional role in the process of cell-cell adhesion.

PMID- 21850209
TI  - Biology of metastatic renal cell carcinoma.
AB  - In the past ten years we have made exceptional progresses in the understanding of
      RCC biology, particularly by recognizing the crucial pathogenetic role of
      activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful
      clinical development of anti-angiogenic and mTOR-targeted drugs, which have
      profoundly impacted on the natural history of the disease and have improved the
      duration and quality of RCC patient lives. However, further improvements are
      still greatly needed: 1) even in patients who obtain striking clinical responses
      early in the course of treatment, disease will ultimately escape control and
      progress to a treatment-resistant state, leading to therapeutic failure; 2)
      prolonged disease control usually requires 'continuous' treatment, even across
      different treatment lines, making the impact of chronic, low-grade, toxicities on
      quality of life greater and precluding, for most patients, the possibility of
      experiencing 'drug-free holidays'; 3) although we have successfully identified
      classes of drugs (or molecular mechanisms of action) that are effective in a
      substantial proportion of patients, we still fall short of molecular predictive
      factors that identify individual patients who will (or will not) benefit from a
      specific intervention and still proceed on a trial-and-error basis, far from a
      truly 'personalized' therapeutic approach; 4) finally (and perhaps most
      importantly), even in the best case scenario, currently available treatments
      inevitably fail to definitively 'cure' metastatic RCC patients. In this review we
      briefly summarize recent developments in the understanding of the molecular
      pathogenesis of RCC, the development of resistance/escape mechanisms, the
      rationale for sequencing agents with different mechanisms of action, and the
      importance of host-related factors. Unraveling the complex mechanisms by which
      RCC shapes host microenvironment and immune response and therapeutic treatments,
      in turn, shape both cancer cell biology and tumor-host interactions may hold the
      key to future advances in such a complex and challenging disease.

PMID- 21850210
TI  - A meta-analysis of the short- and long-term results of randomized controlled
      trials that compared laparoscopy-assisted and conventional open surgery for
      colorectal cancer.
AB  - PURPOSE: We conducted a meta-analysis to evaluate and compare the short- and long
      term results of laparoscopic colorectal surgery (LCRS) and conventional open
      surgery (OCRS) for colorectal cancer (CRC). METHODS: We searched relevant papers
      published between January 1990 and May 2011. We analyzed the outcomes of each
      type of surgery over the short- and long-term periods. RESULTS: In the short-term
      period, we found no significant differences in overall perioperative
      complications and anastomotic leakage between LCRS and OCRS groups. We found no
      significant differences in overall, distant, local and wound-site recurrence,
      overall mortality, 3 and 5 year disease-free survival rate, and cancer-related
      mortality between the 2 groups. CONCLUSIONS: LCRS has the benefits of reducing
      intraoperative blood loss, earlier resumption of oral intake, and shorter
      duration of hospital stay in the short-term. The long-term outcomes of LCRS seem
      to be similar to those of OCRS.

PMID- 21850211
TI  - Gemcitabine Overcomes Erlotinib Resistance in EGFR-Overexpressing Cancer Cells
      through Downregulation of Akt.
AB  - A phase III clinical trial showed gemcitabine chemotherapy combined with
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib
      significantly improved overall survival in patients with advanced pancreatic
      cancer. Therefore, we studied whether addition of gemcitabine to erlotinib in
      cancer cells having intrinsic or acquired erlotinib resistance could restore
      chemosensitization in these cells. We studied the synergistic effect of erlotinib
      and gemcitabine in EGFR-overexpressing A-431 cells with acquired erlotinib
      resistance and in intrinsic erlotinib-resistant triple negative breast cancer
      (TNBC) BT-549, MDA-MB-231 and MDA-MB-468 cell lines. Erlotinib and gemcitabine
      were synergistic in both parental intrinsically erlotinib-sensitive A-431 cells
      (combination index = 0.69 at the effective dose [ED(50)]) and in two A-431 cell
      pools that had acquired erlotinib resistance (combination indices = 0.63 and 0.49
      at ED(50)). The synergistic effect of erlotinib and gemcitabine on cancer cells
      did not require sensitivity to erlotinib provided that erlotinib can inhibit
      EGFR. The restoration of sensitivity by gemcitabine occurred through
      downregulation of phosphorylated Akt (p-Akt), which suggests that PI3K-PTEN-Akt
      activity is important to the synergism between the two agents. In A-431 parental
      cells, treatment with gemcitabine followed by erlotinib - but not the reverse
      sequence - was superior to erlotinib alone. The importance of the order of
      administration maybe due to the downregulation of p-Akt by gemcitabine in a dose-
      and time-dependent manner in cells with intrinsic or acquired erlotinib
      resistance. Our data show that gemcitabine increased the cytotoxic effect of
      erlotinib by downregulating p-Akt in EGFR-overexpressing cells with either
      intrinsic or acquired erlotinib resistance.

PMID- 21850213
TI  - Evaluation of In-Labeled Cyclic RGD Peptides: Effects of Peptide and Linker
      Multiplicity on Their Tumor Uptake, Excretion Kinetics and Metabolic Stability.
AB  - PURPOSE: The purpose of this study was to demonstrate the valence of cyclic RGD
      peptides, P-RGD (PEG(4)-c(RGDfK): PEG(4) = 15-amino-4,710,13
      tetraoxapentadecanoic acid), P-RGD(2) (PEG(4)-E[c(RGDfK)](2), 2P-RGD(4) (E{PEG(4)
      E[c(RGDfK)](2)}(2), 2P4G-RGD(4) (E{PEG(4)-E[G(3)-c(RGDfK)](2)}(2): G(3) = Gly-Gly
      Gly) and 6P-RGD(4) (E{PEG(4)-E[PEG(4)-c(RGDfK)](2)}(2)) in binding to integrin
      alpha(v)beta(3), and to assess the impact of peptide and linker multiplicity on
      biodistribution properties, excretion kinetics and metabolic stability of their
      corresponding (111)In radiotracers. METHODS: Five new RGD peptide conjugates
      (DOTA-P-RGD (DOTA =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid), DOTA
      P-RGD(2), DOTA-2P-RGD(4), DOTA-2P4G-RGD(4), DOTA-6P-RGD(4)), and their (111)In
      complexes were prepared. The integrin alpha(v)beta(3) binding affinity of cyclic
      RGD conjugates were determined by a competitive displacement assay against (125)I
      c(RGDyK) bound to U87MG human glioma cells. Biodistribution, planar imaging and
      metabolism studies were performed in athymic nude mice bearing U87MG human glioma
      xenografts. RESULTS: The integrin alpha(v)beta(3) binding affinity of RGD
      conjugates follows the order of: DOTA-6P-RGD(4) (IC(50) = 0.3 +/- 0.1 nM) ~ DOTA
      2P4G-RGD(4) (IC(50) = 0.2 +/- 0.1 nM) ~ DOTA-2P-RGD(4) (IC(50) = 0.5 +/- 0.1 nM)
      > DOTA-3P-RGD(2) (DOTA-PEG(4)-E[PEG(4)-c(RGDfK)](2): IC(50) = 1.5 +/- 0.2 nM) >
      DOTA-P-RGD(2) (IC(50) = 5.0 +/- 1.0 nM) >> DOTA-P-RGD (IC(50) = 44.3 +/- 3.5 nM)
      ~ c(RGDfK) (IC(50) = 49.9 +/- 5.5 nM) >> DOTA-6P-RGK(4) (IC(50) = 437 +/- 35 nM).
      The fact that DOTA-6P-RGK(4) had much lower integrin alpha(v)beta(3) binding
      affinity than DOTA-6P-RGD(4) suggests that the binding of DOTA-6P-RGD(4) to
      integrin alpha(v)beta(3) is RGD-specific. This conclusion is consistent with the
      lower tumor uptake for (111)In(DOTA-6P-RGK(4)) than that for (111)In(DOTA-6P
      RGD(4)). It was also found that the G(3) and PEG(4) linkers between RGD motifs
      have a significant impact on the integrin alpha(v)beta(3)-targeting capability,
      biodistribution characteristics, excretion kinetics and metabolic stability of
      (111)In-labeled cyclic RGD peptides. CONCLUSION: On the basis of their integrin
      alpha(v)beta(3) binding affinity and tumor uptake of their corresponding (111)In
      radiotracers, it was conclude that 2P-RGD(4), 2P4G-RGD(4) and 6P-RGD(4) are most
      likely bivalent in binding to integrin alpha(v)beta(3), and extra RGD motifs
      might contribute to the long tumor retention times of (111)In(DOTA-2P-RGD(4)),(
      111)In(DOTA-2P4G-RGD(4)) and (111)In(DOTA-6P-RGD(4)) than that of (111)In(DOTA-3P
      RGD(3)) at 72 h p.i. Among the (111)In-labeled cyclic RGD tetramers evaluated in
      the glioma model, (111)In(DOTA-2P4G-RGD(4)) has very high tumor uptake with the
      best tumor/kidney and tumor/liver ratios, suggesting that (90)Y(DOTA-2P4G-RGD(4))
      and (177)Lu(DOTA-2P4G-RGD(4)) might have the potential for targeted radiotherapy
      of integrin alpha(v)beta(3)-positive tumors.

PMID- 21850212
TI  - Tumor induced inactivation of natural killer cell cytotoxic function; implication
      in growth, expansion and differentiation of cancer stem cells.
AB  - Accumulated evidence indicates that cytotoxic function of immune effectors is
      largely suppressed in the tumor microenvironment by a number of distinct
      effectors and their secreted factors. The aims of this review are to provide a
      rationale and a potential mechanism for immunosuppression in cancer and to
      demonstrate the significance of such immunosuppression in cellular
      differentiation and progression of cancer. To that end, we have recently shown
      that NK cells mediate significant cytotoxicity against primary oral squamous
      carcinoma stem cells (OSCSCs) as compared to their more differentiated oral
      squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells
      (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and
      induced pluripotent stem cells (hiPSCs) were all significantly more susceptible
      to NK cell mediated cytotoxicity than their differentiated counterparts or
      parental cells from which they were derived. We have also reported that
      inhibition of differentiation or reversion of cells to a less-differentiated
      phenotype by blocking NFkappaB or targeted knock down of COX2 in primary
      monocytes in vivo significantly augmented NK cell function. Total population of
      monocytes and those depleted of CD16(+) subsets were able to substantially
      prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our
      results suggest that stem cells are significant targets of the NK cell
      cytotoxicity. The concept of split anergy in NK cells and its contribution to
      tissue repair and regeneration and in tumor resistance and progression will be
      discussed in this review.

PMID- 21850217
TI  - The age-specific cumulative incidence of infection with pandemic influenza H1N1
      2009 was similar in various countries prior to vaccination.
AB  - BACKGROUND: During the influenza pandemic of 2009 estimates of symptomatic and
      asymptomatic infection were needed to guide vaccination policies and inform other
      control measures. Serological studies are the most reliable way to measure
      influenza infection independent of symptoms. We reviewed all published
      serological studies that estimated the cumulative incidence of infection with
      pandemic influenza H1N1 2009 prior to the initiation of population-based
      vaccination against the pandemic strain. METHODOLOGY AND PRINCIPAL FINDINGS: We
      searched for studies that estimated the cumulative incidence of pandemic
      influenza infection in the wider community. We excluded studies that did not
      include both pre- and post-pandemic serological sampling and studies that
      included response to vaccination. We identified 47 potentially eligible studies
      and included 12 of them in the review. Where there had been a significant first
      wave, the cumulative incidence of pandemic influenza infection was reported in
      the range 16%-28% in pre-school aged children, 34%-43% in school aged children
      and 12%-15% in young adults. Only 2%-3% of older adults were infected. The
      proportion of the entire population infected ranged from 11%-18%. We re-estimated
      the cumulative incidence to account for the small proportion of infections that
      may not have been detected by serology, and performed direct age-standardisation
      to the study population. For those countries where it could be calculated, this
      suggested a population cumulative incidence in the range 11%-21%. CONCLUSIONS AND
      SIGNIFICANCE: Around the world, the cumulative incidence of infection (which is
      higher than the cumulative incidence of clinical disease) was below that
      anticipated prior to the pandemic. Serological studies need to be routine in
      order to be sufficiently timely to provide support for decisions about
      vaccination.

PMID- 21850218
TI  - Productivity-diversity relationships in lake plankton communities.
AB  - One of the most intriguing environmental gradients connected with variation in
      diversity is ecosystem productivity. The role of diversity in ecosystems is
      pivotal, because species richness can be both a cause and a consequence of
      primary production. However, the mechanisms behind the varying productivity
      diversity relationships (PDR) remain poorly understood. Moreover, large-scale
      studies on PDR across taxa are urgently needed. Here, we examined the
      relationships between resource supply and phyto-, bacterio-, and zooplankton
      richness in 100 small boreal lakes. We studied the PDR locally within the
      drainage systems and regionally across the systems. Second, we studied the
      relationships between resource availability, species richness, biomass and
      resource ratio (N:P) in phytoplankton communities using Structural Equation
      Modeling (SEM) for testing the multivariate hypothesis of PDR. At the local
      scale, the PDR showed variable patterns ranging from positive linear and unimodal
      to negative linear relationships for all planktonic groups. At the regional
      scale, PDRs were significantly linear and positive for phyto- and zooplankton.
      Phytoplankton richness and the amount of chlorophyll a showed a positive linear
      relationship indicating that communities consisting of higher number of species
      were able to produce higher levels of biomass. According to the SEM,
      phytoplankton biomass was largely related to resource availability, yet there was
      a pathway via community richness. Finally, we found that species richness at all
      trophic levels was correlated with several environmental factors, and was also
      related to richness at the other trophic levels. This study showed that the PDRs
      in freshwaters show scale-dependency. We also documented that the PDR complies
      with the multivariate model showing that plant biomass is not mirroring merely
      the resource availability, but is also influenced by richness. This highlights
      the need for conserving diversity in order to maintain ecosystem processes in
      freshwaters.

PMID- 21850219
TI  - Spliceosomal intron insertions in genome compacted ray-finned fishes as evident
      from phylogeny of MC receptors, also supported by a few other GPCRs.
AB  - BACKGROUND: Insertions of spliceosomal introns are very rare events during
      evolution of vertebrates and the mechanisms governing creation of novel intron(s)
      remain obscure. Largely, gene structures of melanocortin (MC) receptors are
      characterized by intron-less architecture. However, recently a few exceptions
      have been reported in some fishes. This warrants a systematic survey of MC
      receptors for understanding intron insertion events during vertebrate evolution.
      METHODOLOGY/PRINCIPAL FINDINGS: We have compiled an extended list of MC receptors
      from different vertebrate genomes with variations in fishes. Notably, the closely
      linked MC2Rs and MC5Rs from a group of ray-finned fishes have three and one
      intron insertion(s), respectively, with conserved positions and intron phase. In
      both genes, one novel insertion was in the highly conserved DRY motif at the end
      of helix TM3. Further, the proto-splice site MAG?R is maintained at intron
      insertion sites in these two genes. However, the orthologs of these receptors
      from zebrafish and tetrapods are intron-less, suggesting these introns are
      simultaneously created in selected fishes. Surprisingly, these novel introns are
      traceable only in four fish genomes. We found that these fish genomes are
      severely compacted after the separation from zebrafish. Furthermore, we also
      report novel intron insertions in P2Y receptors and in CHRM3. Finally, we report
      ultrasmall introns in MC2R genes from selected fishes. CONCLUSIONS/SIGNIFICANCE:
      The current repository of MC receptors illustrates that fishes have no MC3R
      ortholog. MC2R, MC5R, P2Y receptors and CHRM3 have novel intron insertions only
      in ray-finned fishes that underwent genome compaction. These receptors share one
      intron at an identical position suggestive of being inserted contemporaneously.
      In addition to repetitive elements, genome compaction is now believed to be a new
      hallmark that promotes intron insertions, as it requires rapid DNA breakage and
      subsequent repair processes to gain back normal functionality.

PMID- 21850220
TI  - Universally distributed single-copy genes indicate a constant rate of horizontal
      transfer.
AB  - Single copy genes, universally distributed across the three domains of life and
      encoding mostly ancient parts of the translation machinery, are thought to be
      only rarely subjected to horizontal gene transfer (HGT). Indeed it has been
      proposed to have occurred in only a few genes and implies a rare, probably not
      advantageous event in which an ortholog displaces the original gene and has to
      function in a foreign context (orthologous gene displacement, OGD). Here, we have
      utilised an automatic method to identify HGT based on a conservative statistical
      approach capable of robustly assigning both donors and acceptors. Applied to 40
      universally single copy genes we found that as many as 68 HGTs (implying OGDs)
      have occurred in these genes with a rate of 1.7 per family since the last
      universal common ancestor (LUCA). We examined a number of factors that have been
      claimed to be fundamental to HGT in general and tested their validity in the
      subset of universally distributed single copy genes. We found that differing
      functional constraints impact rates of OGD and the more evolutionarily distant
      the donor and acceptor, the less likely an OGD is to occur. Furthermore, species
      with larger genomes are more likely to be subjected to OGD. Most importantly,
      regardless of the trends above, the number of OGDs increases linearly with time,
      indicating a neutral, constant rate. This suggests that levels of HGT above this
      rate may be indicative of positively selected transfers that may allow niche
      adaptation or bestow other benefits to the recipient organism.

PMID- 21850221
TI  - Bcl-2 inhibits the innate immune response during early pathogenesis of murine
      congenital muscular dystrophy.
AB  - Laminin alpha2 (LAMA2)-deficient congenital muscular dystrophy is a severe, early
      onset disease caused by abnormal levels of laminin 211 in the basal lamina
      leading to muscle weakness, transient inflammation, muscle degeneration and
      impaired mobility. In a Lama2-deficient mouse model for this disease, animal
      survival is improved by muscle-specific expression of the apoptosis inhibitor Bcl
      2, conferred by a MyoD-hBcl-2 transgene. Here we investigated early disease
      stages in this model to determine initial pathological events and effects of Bcl
      2 on their progression. Using quantitative immunohistological and mRNA analyses
      we show that inflammation occurs very early in Lama2-deficient muscle, some
      aspects of which are reduced or delayed by the MyoD-hBcl-2 transgene. mRNAs for
      innate immune response regulators, including multiple Toll-like receptors (TLRs)
      and the inflammasome component NLRP3, are elevated in diseased muscle compared
      with age-matched controls expressing Lama2. MyoD-hBcl-2 inhibits induction of
      TLR4, TLR6, TLR7, TLR8 and TLR9 in Lama2-deficient muscle compared with non
      transgenic controls, and leads to reduced infiltration of eosinophils, which are
      key death effector cells. This congenital disease model provides a new paradigm
      for investigating cell death mechanisms during early stages of pathogenesis,
      demonstrating that interactions exist between Bcl-2, a multifunctional regulator
      of cell survival, and the innate immune response.

PMID- 21850222
TI  - Simple, time-saving dye staining of proteins for sodium dodecyl sulfate
      polyacrylamide gel electrophoresis using Coomassie blue.
AB  - A fixation-free and fast protein-staining method for sodium dodecyl sulfate
      polyacrylamide gel electrophoresis using Coomassie blue is described. The
      protocol comprises staining and quick washing steps, which can be completed in
      0.5 h. It has a sensitivity of 10 ng, comparable with that of conventional
      Coomassie Brilliant Blue G staining with phosphoric acid in the staining
      solution. In addition, the dye stain does not contain any amount of acid and
      methanol, such as phosphoric acid. Considering the speed, simplicity, and low
      cost, the dye stain may be of more practical value than other dye-based protein
      stains in routine proteomic research.

PMID- 21850223
TI  - Oyster reefs as natural breakwaters mitigate shoreline loss and facilitate
      fisheries.
AB  - Shorelines at the interface of marine, estuarine and terrestrial biomes are among
      the most degraded and threatened habitats in the coastal zone because of their
      sensitivity to sea level rise, storms and increased human utilization. Previous
      efforts to protect shorelines have largely involved constructing bulkheads and
      seawalls which can detrimentally affect nearshore habitats. Recently, efforts
      have shifted towards "living shoreline" approaches that include biogenic
      breakwater reefs. Our study experimentally tested the efficacy of breakwater
      reefs constructed of oyster shell for protecting eroding coastal shorelines and
      their effect on nearshore fish and shellfish communities. Along two different
      stretches of eroding shoreline, we created replicated pairs of subtidal
      breakwater reefs and established unaltered reference areas as controls. At both
      sites we measured shoreline and bathymetric change and quantified oyster
      recruitment, fish and mobile macro-invertebrate abundances. Breakwater reef
      treatments mitigated shoreline retreat by more than 40% at one site, but overall
      vegetation retreat and erosion rates were high across all treatments and at both
      sites. Oyster settlement and subsequent survival were observed at both sites,
      with mean adult densities reaching more than eighty oysters m(-2) at one site. We
      found the corridor between intertidal marsh and oyster reef breakwaters supported
      higher abundances and different communities of fishes than control plots without
      oyster reef habitat. Among the fishes and mobile invertebrates that appeared to
      be strongly enhanced were several economically-important species. Blue crabs
      (Callinectes sapidus) were the most clearly enhanced (+297%) by the presence of
      breakwater reefs, while red drum (Sciaenops ocellatus) (+108%), spotted seatrout
      (Cynoscion nebulosus) (+88%) and flounder (Paralichthys sp.) (+79%) also
      benefited. Although the vertical relief of the breakwater reefs was reduced over
      the course of our study and this compromised the shoreline protection capacity,
      the observed habitat value demonstrates ecological justification for future, more
      robust shoreline protection projects.

PMID- 21850224
TI  - Optogenetic manipulation of cerebellar Purkinje cell activity in vivo.
AB  - Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex.
      Although their anatomical connections and physiological response properties have
      been extensively studied, the causal role of their activity in behavioral,
      cognitive and autonomic functions is still unclear because PC activity cannot be
      selectively controlled. Here we developed a novel technique using optogenetics
      for selective and rapidly reversible manipulation of PC activity in vivo. We
      injected into rat cerebellar cortex lentiviruses expressing either the light
      activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride
      pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter.
      Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as
      determined by immunohistochemical analysis. In vivo electrophysiological
      recordings showed that all light-responsive PCs in ChR2-transduced rats increased
      frequency of simple spike in response to blue laser illumination. Similarly, most
      light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of
      simple spike in response to orange laser illumination. We then applied these
      techniques to characterize the roles of rat cerebellar uvula, one of the
      cardiovascular regulatory regions in the cerebellum, in resting blood pressure
      (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR
      mediated photoinhibition of the uvula had opposite effects on resting BP,
      inducing depressor and pressor responses, respectively. In contrast, manipulation
      of PC activity within the neighboring lobule VIII had no effect on BP. Blue and
      orange laser illumination onto PBS-injected lobule IX didn't affect BP,
      indicating the observed effects on BP were actually due to PC activation and
      inhibition. These results clearly demonstrate that the optogenetic method we
      developed here will provide a powerful way to elucidate a causal relationship
      between local PC activity and functions of the cerebellum.

PMID- 21850225
TI  - Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus
      corneal stroma.
AB  - PURPOSE: To determine the effect of Ultraviolet-A collagen cross-linking with
      hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen
      ultrastructure in normal and keratoconus ex vivo human corneas. METHODS: Using
      small-angle X-ray scattering, measurements of collagen D-periodicity, fibril
      diameter and interfibrillar spacing were made at 1 mm intervals across six normal
      post-mortem corneas (two above physiological hydration (swollen) and four below
      (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen;
      one unswollen), before and after hypo-osmolar cross-linking. The same parameters
      were measured in three other unswollen normal corneas before and after iso
      osmolar cross-linking and in three pairs of swollen normal corneas, in which only
      the left was cross-linked (with iso-osmolar riboflavin). RESULTS: Hypo-osmolar
      cross-linking resulted in an increase in corneal hydration in all corneas. In the
      keratoconus corneas and unswollen normal corneas, this was accompanied by an
      increase in collagen interfibrillar spacing (p<0.001); an increase in fibril
      diameter was also seen in two out of four unswollen normal corneas and one
      unswollen keratoconus cornea (p<0.001). Iso-osmolar cross-linking resulted in a
      decrease in tissue hydration in the swollen normal corneas only. Although there
      was no consistent treatment-induced change in hydration in the unswollen normal
      samples, iso-osmolar cross-linking of these corneas did result in a compaction of
      collagen fibrils and a reduced fibril diameter (p<0.001); these changes were not
      seen in the swollen normal corneas. Collagen D-periodicity was not affected by
      either treatment. CONCLUSION: The observed structural changes following
      Ultraviolet-A cross-linking with hypo-osmolar or iso-osmolar riboflavin solutions
      are more likely a consequence of treatment-induced changes in tissue hydration
      rather than cross-linking.

PMID- 21850227
TI  - Noise amplification in human tumor suppression following gamma irradiation.
AB  - The influence of noise on oscillatory motion is a subject of permanent interest,
      both for fundamental and practical reasons. Cells respond properly to external
      stimuli by using noisy systems. We have clarified the effect of intrinsic noise
      on the dynamics in the human cancer cells following gamma irradiation. It is
      shown that the large amplification and increasing mutual information with delay
      are due to coherence resonance. Furthermore, frequency domain analysis is used to
      study the mechanisms.

PMID- 21850226
TI  - In situ dividing and phagocytosing retinal microglia express nestin, vimentin,
      and NG2 in vivo.
AB  - BACKGROUND: Following injury, microglia become activated with subsets expressing
      nestin as well as other neural markers. Moreover, cerebral microglia can give
      rise to neurons in vitro. In a previous study, we analysed the proliferation
      potential and nestin re-expression of retinal macroglial cells such as astrocytes
      and Muller cells after optic nerve (ON) lesion. However, we were unable to
      identify the majority of proliferative nestin(+) cells. Thus, the present study
      evaluates expression of nestin and other neural markers in quiescent and
      proliferating microglia in naive retina and following ON transection in adult
      rats in vivo. METHODOLOGY/PRINCIPAL FINDINGS: For analysis of cell proliferation
      and cells fates, rats received BrdU injections. Microglia in retinal sections or
      isolated cells were characterized using immunofluorescence labeling with markers
      for microglia (e.g., Iba1, CD11b), cell proliferation, and neural cells (e.g.,
      nestin, vimentin, NG2, GFAP, Doublecortin etc.). Cellular analyses were performed
      using confocal laser scanning microscopy. In the naive adult rat retina, about
      60% of resting ramified microglia expressed nestin. After ON transection, numbers
      of nestin(+) microglia peaked to a maximum at 7 days, primarily due to in situ
      cell proliferation of exclusively nestin(+) microglia. After 8 weeks, microglia
      numbers re-attained control levels, but 20% were still BrdU(+) and nestin(+),
      although no further local cell proliferation occurred. In addition, nestin(+)
      microglia co-expressed vimentin and NG2, but not GFAP or neuronal markers.
      Fourteen days after injury and following retrograde labeling of retinal ganglion
      cells (RGCs) with Fluorogold (FG), nestin(+)NG2(+) microglia were positive for
      the dye indicating an active involvement of a proliferating cell population in
      phagocytosing apoptotic retinal neurons. CONCLUSIONS/SIGNIFICANCE: The current
      study provides evidence that in adult rat retina, a specific resident population
      of microglia expresses proteins of immature neural cells that are involved in
      injury-induced cell proliferation and phagocytosis while transdifferentiation was
      not observed.

PMID- 21850228
TI  - Automatic compilation from high-level biologically-oriented programming language
      to genetic regulatory networks.
AB  - BACKGROUND: The field of synthetic biology promises to revolutionize our ability
      to engineer biological systems, providing important benefits for a variety of
      applications. Recent advances in DNA synthesis and automated DNA assembly
      technologies suggest that it is now possible to construct synthetic systems of
      significant complexity. However, while a variety of novel genetic devices and
      small engineered gene networks have been successfully demonstrated, the
      regulatory complexity of synthetic systems that have been reported recently has
      somewhat plateaued due to a variety of factors, including the complexity of
      biology itself and the lag in our ability to design and optimize sophisticated
      biological circuitry. METHODOLOGY/PRINCIPAL FINDINGS: To address the gap between
      DNA synthesis and circuit design capabilities, we present a platform that enables
      synthetic biologists to express desired behavior using a convenient high-level
      biologically-oriented programming language, Proto. The high level specification
      is compiled, using a regulatory motif based mechanism, to a gene network,
      optimized, and then converted to a computational simulation for numerical
      verification. Through several example programs we illustrate the automated
      process of biological system design with our platform, and show that our compiler
      optimizations can yield significant reductions in the number of genes (~ 50%) and
      latency of the optimized engineered gene networks. CONCLUSIONS/SIGNIFICANCE: Our
      platform provides a convenient and accessible tool for the automated design of
      sophisticated synthetic biological systems, bridging an important gap between DNA
      synthesis and circuit design capabilities. Our platform is user-friendly and
      features biologically relevant compiler optimizations, providing an important
      foundation for the development of sophisticated biological systems.

PMID- 21850229
TI  - HIV pre-exposure prophylaxis (PrEP)--a quantitative ethics appraisal.
AB  - BACKGROUND: There is now strong evidence that preventive oral antiretroviral
      therapy can moderately reduce likelihood of HIV infection. This concept is called
      HIV pre-exposure prophylaxis (PrEP). Premature closures of some previous PrEP
      clinical trials, secondary to ethical concerns, did not stop research. We aimed
      to appraise the extent of ethics considerations reporting in PrEP study
      documents. METHODS: We conducted a systematic quantitative ethics appraisal,
      grounded in PrEP literature and using eight principles proposed by Ezechiel
      Emanuel. We developed an a priori checklist of 101 evidence-based ethics items.
      We obtained protocols for eleven of nineteen clinical controlled studies
      identified. Two reviewers independently appraised study documents against the
      checklist. Ethics appraisal was synthesized using adjusted percentages of items
      reported. RESULTS: On average, 58% of the 101 ethics items were mentioned or
      addressed in documents, with variations noted both across studies and across
      principles. Considerations pertaining to social value were least reported (43% of
      checklist items, on average) whereas considerations related to informed consent
      and favorable risk-benefit ratio were most reported (75% of checklist items, on
      average). DISCUSSION: Some PrEP studies reportedly address more ethics
      considerations than others but, overall, ethics considerations reporting could be
      much improved. While this review does not allow us to comment on the actual
      execution of HIV PrEP trials, it is a reminder that optimism generated by
      potentially effective interventions should not overshadow the importance of
      ethics in research design and development. Improving ethics reporting might
      improve the perceived value of PrEP research and subsequent data.

PMID- 21850230
TI  - High-throughput identification of potential minor histocompatibility antigens by
      MHC tetramer-based screening: feasibility and limitations.
AB  - T-cell recognition of minor histocompatibility antigens (MiHA) plays an important
      role in the graft-versus-tumor (GVT) effect of allogeneic stem cell
      transplantation (allo-SCT). However, the number of MiHA identified to date
      remains limited, making clinical application of MiHA reactive T-cell infusion
      difficult. This study represents the first attempt of genome-wide prediction of
      MiHA, coupled to the isolation of T-cell populations that react with these
      antigens. In this unbiased high-throughput MiHA screen, both the possibilities
      and pitfalls of this approach were investigated. First, 973 polymorphic peptides
      expressed by hematopoietic stem cells were predicted and screened for HLA-A2
      binding. Subsequently a set of 333 high affinity HLA-A2 ligands was identified
      and post transplantation samples from allo-SCT patients were screened for T-cell
      reactivity by a combination of pMHC-tetramer-based enrichment and multi-color
      flow cytometry. Using this approach, 71 peptide-reactive T-cell populations were
      generated. The isolation of a T-cell line specifically recognizing target cells
      expressing the MAP4K1(IMA) antigen demonstrates that identification of MiHA
      through this approach is in principle feasible. However, with the exception of
      the known MiHA HMHA1, none of the other T-cell populations that were generated
      demonstrated recognition of endogenously MiHA expressing target cells, even
      though recognition of peptide-loaded targets was often apparent. Collectively
      these results demonstrate the technical feasibility of high-throughput analysis
      of antigen-specific T-cell responses in small patient samples. However, the high
      sensitivity of this approach requires the use of potential epitope sets that are
      not solely based on MHC binding, to prevent the frequent detection of T-cell
      responses that lack biological relevance.

PMID- 21850231
TI  - Emergence of tuning to natural stimulus statistics along the central auditory
      pathway.
AB  - We have previously shown that neurons in primary auditory cortex (A1) of
      anaesthetized (ketamine/medetomidine) ferrets respond more strongly and reliably
      to dynamic stimuli whose statistics follow "natural" 1/f dynamics than to stimuli
      exhibiting pitch and amplitude modulations that are faster (1/f(0.5)) or slower
      (1/f(2)) than 1/f. To investigate where along the central auditory pathway this
      1/f-modulation tuning arises, we have now characterized responses of neurons in
      the central nucleus of the inferior colliculus (ICC) and the ventral division of
      the mediate geniculate nucleus of the thalamus (MGV) to 1/f(gamma) distributed
      stimuli with gamma varying between 0.5 and 2.8. We found that, while the great
      majority of neurons recorded from the ICC showed a strong preference for the most
      rapidly varying (1/f(0.5) distributed) stimuli, responses from MGV neurons did
      not exhibit marked or systematic preferences for any particular gamma exponent.
      Only in A1 did a majority of neurons respond with higher firing rates to stimuli
      in which gamma takes values near 1. These results indicate that 1/f tuning
      emerges at forebrain levels of the ascending auditory pathway.

PMID- 21850232
TI  - Scientists want more children.
AB  - Scholars partly attribute the low number of women in academic science to the
      impact of the science career on family life. Yet, the picture of how men and
      women in science--at different points in the career trajectory--compare in their
      perceptions of this impact is incomplete. In particular, we know little about the
      perceptions and experiences of junior and senior scientists at top universities,
      institutions that have a disproportionate influence on science, science policy,
      and the next generation of scientists. Here we show that having fewer children
      than wished as a result of the science career affects the life satisfaction of
      science faculty and indirectly affects career satisfaction, and that young
      scientists (graduate students and postdoctoral fellows) who have had fewer
      children than wished are more likely to plan to exit science entirely. We also
      show that the impact of science on family life is not just a woman's problem; the
      effect on life satisfaction of having fewer children than desired is more
      pronounced for male than female faculty, with life satisfaction strongly related
      to career satisfaction. And, in contrast to other research, gender differences
      among graduate students and postdoctoral fellows disappear. Family factors impede
      talented young scientists of both sexes from persisting to research positions in
      academic science. In an era when the global competitiveness of US science is at
      risk, it is concerning that a significant proportion of men and women trained in
      the select few spots available at top US research universities are considering
      leaving science and that such desires to leave are related to the impact of the
      science career on family life. Results from our study may inform university
      family leave policies for science departments as well as mentoring programs in
      the sciences.

PMID- 21850233
TI  - Asymmetric reproductive isolation between two sympatric annual killifish with
      extremely short lifespans.
AB  - BACKGROUND: Interspecific reproductive isolation is typically achieved by a
      combination of intrinsic and extrinsic barriers. Behavioural isolating barriers
      between sympatric, closely related species are often of primary importance and
      frequently aided by extrinsic factors causing spatial and temporal interspecific
      separation. Study systems with a severely limited role of extrinsic factors on
      reproductive isolation may provide valuable insights into how reproductive
      isolation between sympatric species is maintained. We used no-choice experimental
      set-up to study reproductive barriers between two closely related sympatric
      African killifish species, Nothobranchius furzeri and Nothobranchius orthonotus.
      These fish live in small temporary savannah pools and have complete spatial and
      temporal overlap in reproductive activities and share a similar ecology.
      PRINCIPAL FINDINGS: We found that the two species display largely incomplete and
      asymmetric reproductive isolation. Mating between N. furzeri males and N.
      orthonotus females was absent under standard experimental conditions and eggs
      were not viable when fish were forced to mate in a modified experimental setup.
      In contrast, male N. orthonotus indiscriminately mated with N. furzeri females,
      the eggs were viable, and offspring successfully hatched. Most spawnings,
      however, were achieved by male coercion and egg production and embryo survival
      were low. Behavioural asymmetry was likely facilitated by mating coercion from
      larger males of N. orthonotus and at relatively low cost to females.
      Interestingly, the direction of asymmetry was positively associated with
      asymmetry in post-mating reproductive barriers. SIGNIFICANCE: We showed that, in
      fish species with a promiscuous mating system and multiple matings each day,
      selection for strong mate preferences was relaxed. This effect was likely due to
      the small proportion of resources allocated to each single mating and the high
      potential cost to females from mating refusal. We highlight and discuss the fact
      that males of rarer species may often coercively mate with females of a related,
      more abundant species.

PMID- 21850234
TI  - Incubating isolated mouse EDL muscles with creatine improves force production and
      twitch kinetics in fatigue due to reduction in ionic strength.
AB  - BACKGROUND: Creatine supplementation can improve performance during high
      intensity exercise in humans and improve muscle strength in certain myopathies.
      In this present study, we investigated the direct effects of acute creatine
      incubation on isolated mouse fast-twitch EDL muscles, and examined how these
      effects change with fatigue. METHODS AND RESULTS: The extensor digitorum longus
      muscle from mice aged 12-14 weeks was isolated and stimulated with field
      electrodes to measure force characteristics in 3 different states: (i) before
      fatigue; (ii) immediately after a fatigue protocol; and (iii) after recovery.
      These served as the control measurements for the muscle. The muscle was then
      incubated in a creatine solution and washed. The measurement of force
      characteristics in the 3 different states was then repeated. In un-fatigued
      muscle, creatine incubation increased the maximal tetanic force. In fatigued
      muscle, creatine treatment increased the force produced at all frequencies of
      stimulation. Incubation also increased the rate of twitch relaxation and twitch
      contraction in fatigued muscle. During repetitive fatiguing stimulation, creatine
      treated muscles took 55.1+/-9.5% longer than control muscles to lose half of
      their original force. Measurement of weight changes showed that creatine
      incubation increased EDL muscle mass by 7%. CONCLUSION: Acute creatine
      application improves force production in isolated fast-twitch EDL muscle, and
      these improvements are particularly apparent when the muscle is fatigued. One
      likely mechanism for this improvement is an increase in Ca(2+) sensitivity of
      contractile proteins as a result of ionic strength decreases following creatine
      incubation.

PMID- 21850235
TI  - Addressing inter-gene heterogeneity in maximum likelihood phylogenomic analysis:
      yeasts revisited.
AB  - Phylogenomic approaches to the resolution of inter-species relationships have
      become well established in recent years. Often these involve concatenation of
      many orthologous genes found in the respective genomes followed by analysis using
      standard phylogenetic models. Genome-scale data promise increased resolution by
      minimising sampling error, yet are associated with well-known but often
      inappropriately addressed caveats arising through data heterogeneity and model
      violation. These can lead to the reconstruction of highly-supported but incorrect
      topologies. With the aim of obtaining a species tree for 18 species within the
      ascomycetous yeasts, we have investigated the use of appropriate evolutionary
      models to address inter-gene heterogeneities and the scalability and validity of
      supermatrix analysis as the phylogenetic problem becomes more difficult and the
      number of genes analysed approaches truly phylogenomic dimensions. We have
      extended a widely-known early phylogenomic study of yeasts by adding additional
      species to increase diversity and augmenting the number of genes under analysis.
      We have investigated sophisticated maximum likelihood analyses, considering not
      only a concatenated version of the data but also partitioned models where each
      gene constitutes a partition and parameters are free to vary between the
      different partitions (thereby accounting for variation in the evolutionary
      processes at different loci). We find considerable increases in likelihood using
      these complex models, arguing for the need for appropriate models when analyzing
      phylogenomic data. Using these methods, we were able to reconstruct a well
      supported tree for 18 ascomycetous yeasts spanning about 250 million years of
      evolution.

PMID- 21850236
TI  - Regulation of cathepsin G reduces the activation of proinsulin-reactive T cells
      from type 1 diabetes patients.
AB  - Autoantigenic peptides resulting from self-proteins such as proinsulin are
      important players in the development of type 1 diabetes mellitus (T1D). Self
      proteins can be processed by cathepsins (Cats) within endocytic compartments and
      loaded to major histocompatibility complex (MHC) class II molecules for CD4(+) T
      cell inspection. However, the processing and presentation of proinsulin by
      antigen-presenting cells (APC) in humans is only partially understood. Here we
      demonstrate that the processing of proinsulin by B cell or myeloid dendritic cell
      (mDC1)-derived lysosomal cathepsins resulted in several proinsulin-derived
      intermediates. These intermediates were similar to those obtained using purified
      CatG and, to a lesser extent, CatD, S, and V in vitro. Some of these
      intermediates polarized T cell activation in peripheral blood mononuclear cells
      (PBMC) from T1D patients indicative for naturally processed T cell epitopes.
      Furthermore, CatG activity was found to be elevated in PBMC from T1D patients and
      abrogation of CatG activity resulted in functional inhibition of proinsulin
      reactive T cells. Our data suggested the notion that CatG plays a critical role
      in proinsulin processing and is important in the activation process of
      diabetogenic T cells.

PMID- 21850237
TI  - Dysregulation in retinal para-inflammation and age-related retinal degeneration
      in CCL2 or CCR2 deficient mice.
AB  - We have shown previously that a para-inflammatory response exists at the
      retinal/choroidal interface in the aging eye; and this response plays an
      important role in maintaining retinal homeostasis under chronic stress
      conditions. We hypothesized that dysregulation of the para-inflammatory response
      may result in an overt pro-inflammatory response inducing retinal degeneration.
      In this study, we examined this hypothesis in mice deficient in chemokine CCL2 or
      its cognate receptor CCR2. CCL2- or CCR2-deficient mice developed retinal
      degenerative changes with age, characterized as retinal pigment epithelial (RPE)
      cell and photoreceptor cell death. Retinal cell death was associated with
      significantly more subretinal microglial accumulation and increased complement
      activation. In addition, monocytes from CCL2- or CCR2-deficient mice had reduced
      capacity for phagocytosis and chemotaxis, expressed less IL-10 but more iNOS, IL
      12 and TNF-alpha when compared to monocytes from WT mice. Complement activation
      at the site of RPE cell death resulted in C3b/C3d but not C5b-9 deposition,
      indicating only partial activation of the complement pathway. Our results suggest
      that altered monocyte functions may convert the protective para-inflammatory
      response into an overtly harmful inflammation at the retina/choroidal interface
      in CCL2- or CCR2-deficient mice, leading to RPE and photoreceptor degeneration.
      These data support a concept whereby a protective para-inflammatory response
      relies upon a normally functioning innate immune system. If the innate immune
      system is deficient chronic stress may tip the balance towards an overt
      inflammatory response causing cell/tissue damage.

PMID- 21850238
TI  - Purinergic activation of Ca2+-permeable TRPV4 channels is essential for mechano
      sensitivity in the aldosterone-sensitive distal nephron.
AB  - Mechanical forces are known to induce increases of [Ca(2+)](i) in the aldosterone
      sensitive distal nephron (ASDN) cells to regulate epithelial transport. At the
      same time, mechanical stress stimulates ATP release from ASDN cells. In this
      study, we combined ratiometric Fura-2 based monitoring of [Ca(2+)](i) in freshly
      isolated split-opened ASDN with targeted deletion of P2Y2 and TRPV4 in mice to
      probe a role for purinergic signaling in mediating mechano-sensitive responses in
      ASDN cells. ATP application causes a reproducible transient Ca(2+) peak followed
      by a sustained plateau. Individual cells of the cortical collecting duct (CCD)
      and the connecting tubule (CNT) respond to purinergic stimulation with
      comparative elevations of [Ca(2+)](i). Furthermore, ATP-induced Ca(2+)-responses
      are nearly identical in both principal (AQP2-positive) and intercalated (AQP2
      negative) cells as was confirmed using immunohistochemistry in split-opened ASDN.
      UTP application produces elevations of [Ca(2+)](i) similar to that observed with
      ATP suggesting a dominant role of P2Y2-like receptors in generation of
      [Ca(2+)](i) response. Indeed, genetic deletion of P2Y2 receptors decreases the
      magnitude of ATP-induced and UTP-induced Ca(2+) responses by more than 70% and
      90%, respectively. Both intracellular and extracellular sources of Ca(2+)
      appeared to contribute to the generation of ATP-induced Ca(2+) response in ASDN
      cells. Importantly, flow- and hypotonic-induced Ca(2+) elevations are markedly
      blunted in P2Y2 -/- mice. We further demonstrated that activation of mechano
      sensitive TRPV4 channel plays a major role in the sustained [Ca(2+)](i) elevation
      during purinergic stimulation. Consistent with this, ATP-induced Ca(2+) plateau
      are dramatically attenuated in TRV4 -/- mice. Inhibition of TRPC channels with 10
      uM BTP2 also decreased ATP-induced Ca(2+) plateau whilst to a lower degree than
      that observed with TRPV4 inhibition/genetic deletion. We conclude that
      stimulation of purinergic signaling by mechanical stimuli leads to activation of
      TRPV4 and, to a lesser extent, TRPCs channels, and this is an important component
      of mechano-sensitive response of the ASDN.

PMID- 21850239
TI  - Unraveling spurious properties of interaction networks with tailored random
      networks.
AB  - We investigate interaction networks that we derive from multivariate time series
      with methods frequently employed in diverse scientific fields such as biology,
      quantitative finance, physics, earth and climate sciences, and the neurosciences.
      Mimicking experimental situations, we generate time series with finite length and
      varying frequency content but from independent stochastic processes. Using the
      correlation coefficient and the maximum cross-correlation, we estimate
      interdependencies between these time series. With clustering coefficient and
      average shortest path length, we observe unweighted interaction networks, derived
      via thresholding the values of interdependence, to possess non-trivial topologies
      as compared to Erdos-Renyi networks, which would indicate small-world
      characteristics. These topologies reflect the mostly unavoidable finiteness of
      the data, which limits the reliability of typically used estimators of signal
      interdependence. We propose random networks that are tailored to the way
      interaction networks are derived from empirical data. Through an exemplary
      investigation of multichannel electroencephalographic recordings of epileptic
      seizures--known for their complex spatial and temporal dynamics--we show that
      such random networks help to distinguish network properties of interdependence
      structures related to seizure dynamics from those spuriously induced by the
      applied methods of analysis.

PMID- 21850240
TI  - Panton-Valentine leukocidin does play a role in the early stage of Staphylococcus
      aureus skin infections: a rabbit model.
AB  - Despite epidemiological data linking necrotizing skin infections with the
      production of Panton-Valentine leukocidin (PVL), the contribution of this toxin
      to the virulence of S. aureus has been highly discussed as a result of
      inconclusive results of in vivo studies. However, the majority of these results
      originate from experiments using mice, an animal species which neutrophils--the
      major target cells for PVL--are highly insensitive to the action of this
      leukocidin. In contrast, the rabbit neutrophils have been shown to be as
      sensitive to PVL action as human cells, making the rabbit a better experimental
      animal to explore the PVL role. In this study we examined whether PVL contributes
      to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits
      were injected intradermally with 10(8) cfu of either a PVL positive community
      associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or
      a PVL complemented knockout strain, and the development of skin lesions was
      observed. While all strains induced skin infection, the wild type strain produced
      larger lesions and a higher degree of skin necrosis compared to the PVL knockout
      strain in the first week after the infection. The PVL expression in the rabbits
      was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies
      observed only in the rabbits infected with PVL positive strains. These results
      indicate that the rabbit model is more suitable for studying the role of PVL in
      staphylococcal diseases than other animal models. Further, they support the
      epidemiological link between PVL producing S. aureus strains and necrotizing skin
      infections.

PMID- 21850241
TI  - Genetic diversity, recombination, and divergence in animal associated Penicillium
      dipodomyis.
AB  - Penicillium dipodomyis is thought to be an exclusively asexual fungus associated
      with Kangaroo Rats, Dipodomys species, and is unique among Penicillium species in
      growing at 37 degrees C but producing no known toxins. Lack of recombination
      within P. dipodomyis would result in limited adaptive flexibility but possibly
      enhance local adaptation and host selection via maintenance of favourable
      genotypes. Here, analysis of DNA sequence data from five protein-coding genes
      shows that recombination occurs within P. dipodomyis on a small spatial scale.
      Furthermore, detection of mating-type alleles supports outcrossing and a sexual
      cycle in P. dipodomyis. P. dipodomyis was a weaker competitor in in vitro assays
      with other Penicillium species found in association with Kanagaroo rats. Bayesian
      species level analysis suggests that the P. dipodomyis lineage diverged from
      closely related species also found in cheek pouches of Kangaroo Rats and their
      stored seeds about 11 million years ago, a similar divergence time as Dipodomys
      from its sister rodent taxa.

PMID- 21850242
TI  - CAF01 potentiates immune responses and efficacy of an inactivated influenza
      vaccine in ferrets.
AB  - Trivalent inactivated vaccines (TIV) against influenza are given to 350 million
      people every year. Most of these are non-adjuvanted vaccines whose immunogenicity
      and protective efficacy are considered suboptimal. Commercially available non
      adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the
      induction of cell-mediated immune responses is negligible. Recently, a cationic
      liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01)
      was developed. CAF01 has proven to enhance both humoral and cell-mediated immune
      responses to a number of different experimental vaccine candidates. In this
      study, we compared the immune responses in ferrets to a commercially available
      TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two
      recently circulating H1N1 viruses were used as challenge to test the vaccine
      efficacy. CAF01 improved the immunogenicity of the vaccine, with increased
      influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular
      mediated immunity as indicated by interferon-gamma expressing lymphocytes,
      measured by flow cytometry. CAF01 also enhanced the protection conferred by the
      vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally,
      CAF01 allowed for dose-reduction and led to higher levels of protection compared
      to TIV adjuvanted with a squalene emulsion. The data obtained in this human
      relevant challenge model supports the potential of CAF01 in future influenza
      vaccines.

PMID- 21850244
TI  - Association between markers of fatty liver disease and impaired glucose
      regulation in men and women from the general population: the KORA-F4-study.
AB  - OBJECTIVE: To investigate whether the elevated liver enzymes gamma
      glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate
      oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic
      fatty liver disease (NAFLD) respectively are independently associated with pre
      diabetic states, namely impaired fasting glucose (IFG) and impaired glucose
      tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women
      from the general German population. METHODS: The study was based on 3009 subjects
      (1556 females, 1453 males) aged 32 to 81 years who participated in the KORA-F4
      Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants
      underwent an oral glucose tolerance test to assess disturbances in glucose
      metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni
      Fatty Liver Index (FLI). RESULTS: 229 participants (7.6%) reported known
      diabetes, 106 had NDD (3.5%), 107 (3.6%) had IFG, 309 (10.3%) had IGT, 69 (2.3%)
      were affected with both metabolic disorders (IFG/IGT) and 74 (2.5%) could not be
      classified. GGT and GPT were significantly elevated in persons with pre-diabetes
      and diabetes (GGT in diabetic persons OR = 1.76, [1.47-2.09], in IFG OR = 1.79
      [1.50-2.13], GPT in diabetic persons OR = 1.51, [1.30-1.74], in NDD OR = 1.77
      [1.52-2.06]), GOT and AP only inconsistently in some pre-diabetes groups. The
      effects were sharpened in models using an increase of two or three out of three
      enzymes as an estimate of fatty liver and especially in models using the FLI.
      Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men:
      53.2%). In participants with fatty liver disease, the OR for NDD adjusted for sex
      and age was 8.48 [5.13-14.00], 6.70 [3.74-12.01] for combined IFG and IGT and
      4.78 [3.47-6.59] for known diabetes respectively. CONCLUSIONS: Elevated GGT and
      GPT-values as well as estimates of fatty liver disease are significantly
      associated with pre-diabetes and diabetes and thus very useful first indicators
      of a disturbed glucose metabolism.

PMID- 21850243
TI  - Human mesenchymal stem cells prolong survival and ameliorate motor deficit
      through trophic support in Huntington's disease mouse models.
AB  - We investigated the therapeutic potential of human bone marrow-derived
      mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten
      weeks after intrastriatal injection of quinolinic acid (QA), mice that received
      hBM-MSC transplantation showed a significant reduction in motor function
      impairment and increased survival rate. Transplanted hBM-MSCs were capable of
      survival, and inducing neural proliferation and differentiation in the QA
      lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia,
      neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region.
      Similar results were obtained in R6/2-J2, a genetically-modified animal model of
      HD, except for the improvement of motor function. After hBM-MSC transplantation,
      the transplanted hBM-MSCs may integrate with the host cells and increase the
      levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1
      (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased
      while Bax and caspase-3 levels were decreased after hBM-MSC transplantation
      suggesting that the reduced level of apoptosis after hBM-MSC transplantation was
      of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural
      differentiation improvement potential, neurotrophic support capability and an
      anti-apoptotic effect, and may be a feasible candidate for HD therapy.

PMID- 21850245
TI  - Actin fusion proteins alter the dynamics of mechanically induced cytoskeleton
      rearrangement.
AB  - Mechanical forces can regulate various functions in living cells. The
      cytoskeleton is a crucial element for the transduction of forces in cell-internal
      signals and subsequent biological responses. Accordingly, many studies in
      cellular biomechanics have been focused on the role of the contractile acto
      myosin system in such processes. A widely used method to observe the dynamic
      actin network in living cells is the transgenic expression of fluorescent
      proteins fused to actin. However, adverse effects of GFP-actin fusion proteins on
      cell spreading, migration and cell adhesion strength have been reported. These
      shortcomings were shown to be partly overcome by fusions of actin binding
      peptides to fluorescent proteins. Nevertheless, it is not understood whether
      direct labeling by actin fusion proteins or indirect labeling via these chimaeras
      alters biomechanical responses of cells and the cytoskeleton to forces. We
      investigated the dynamic reorganization of actin stress fibers in cells under
      cyclic mechanical loading by transiently expressing either egfp-Lifeact or eyfp
      actin in rat embryonic fibroblasts and observing them by means of live cell
      microscopy. Our results demonstrate that mechanically-induced actin stress fiber
      reorganization exhibits very different kinetics in EYFP-actin cells and EGFP
      Lifeact cells, the latter showing a remarkable agreement with the reorganization
      kinetics of non-transfected cells under the same experimental conditions.

PMID- 21850246
TI  - Highly sensitive determination of hydrogen peroxide and glucose by fluorescence
      correlation spectroscopy.
AB  - BACKGROUND: Because H(2)O(2) is generated by various oxidase-catalyzed reactions,
      a highly sensitive determination method of H(2)O(2) is applicable to measurements
      of low levels of various oxidases and their substrates such as glucose, lactate,
      glutamate, urate, xanthine, choline, cholesterol and NADPH. We propose herein a
      new, highly sensitive method for the measurement of H(2)O(2) and glucose using
      fluorescence correlation spectroscopy (FCS). METHODOLOGY/PRINCIPAL FINDINGS: FCS
      has the advantage of allowing us to determine the number of fluorescent
      molecules. FCS measures the fluctuations in fluorescence intensity caused by
      fluorescent probe movement in a small light cavity with a defined volume
      generated by confocal illumination. We thus developed a highly sensitive
      determination system of H(2)O(2) by FCS, where horseradish peroxidase (HRP)
      catalyzes the formation of a covalent bond between fluorescent molecules and
      proteins in the presence of H(2)O(2). Our developed system gave a linear
      calibration curve for H(2)O(2) in the range of 28 to 300 nM with the detection
      limit of 8 nM. In addition, by coupling with glucose oxidase (GOD)-catalyzed
      reaction, the method allows to measure glucose in the range of 80 nM to 1.5 uM
      with detection limit of 24 nM. The method was applicable to the assay of glucose
      in blood plasma. The mean concentration of glucose in normal human blood plasma
      was determined to be 4.9 mM. CONCLUSIONS/SIGNIFICANCE: In comparison with
      commercial available methods, the detection limit and the minimum value of
      determination for glucose are at least 2 orders of magnitude more sensitive in
      our system. Such a highly sensitive method leads the fact that only a very small
      amount of plasma (20 nL) is needed for the determination of glucose concentration
      in blood plasma.

PMID- 21850247
TI  - Reduced reactivation from dormancy but maintained lineage choice of human
      mesenchymal stem cells with donor age.
AB  - Mesenchymal stem cells (MSC) are promising for cell-based regeneration therapies
      but up to date it is still controversial whether their function is maintained
      throughout ageing. Aim of this study was to address whether frequency, activation
      in vitro, replicative function, and in vitro lineage choice of MSC is maintained
      throughout ageing to answer the question whether MSC-based regeneration
      strategies should be restricted to younger individuals. MSC from bone marrow
      aspirates of 28 donors (5-80 years) were characterized regarding colony-forming
      unit-fibroblast (CFU-F) numbers, single cell cloning efficiency (SSCE),
      osteogenic, adipogenic and chondrogenic differentiation capacity in vitro.
      Alkaline phosphatase (ALP) activity, mineralization, Oil Red O content,
      proteoglycan- and collagen type II deposition were quantified. While CFU-F
      frequency was maintained, SSCE and early proliferation rate decreased
      significantly with advanced donor age. MSC with higher proliferation rate before
      start of induction showed stronger osteogenic, adipogenic and chondrogenic
      differentiation. MSC with high osteogenic capacity underwent better
      chondrogenesis and showed a trend to better adipogenesis. Lineage choice was,
      however, unaltered with age. CONCLUSION: Ageing influenced activation from
      dormancy and replicative function of MSC in a way that it may be more demanding
      to mobilize MSC to fast cell growth at advanced age. Since fast proliferation
      came along with high multilineage capacity, the proliferation status of expanded
      MSC rather than donor age may provide an argument to restrict MSC-based therapies
      to certain individuals.

PMID- 21850248
TI  - Accounting for ecosystem alteration doubles estimates of conservation risk in the
      conterminous United States.
AB  - Previous national and global conservation assessments have relied on habitat
      conversion data to quantify conservation risk. However, in addition to habitat
      conversion to crop production or urban uses, ecosystem alteration (e.g., from
      logging, conversion to plantations, biological invasion, or fire suppression) is
      a large source of conservation risk. We add data quantifying ecosystem alteration
      on unconverted lands to arrive at a more accurate depiction of conservation risk
      for the conterminous United States. We quantify ecosystem alteration using a
      recent national assessment based on remote sensing of current vegetation compared
      with modeled reference natural vegetation conditions. Highly altered (but not
      converted) ecosystems comprise 23% of the conterminous United States, such that
      the number of critically endangered ecoregions in the United States is 156%
      higher than when calculated using habitat conversion data alone. Increased
      attention to natural resource management will be essential to address widespread
      ecosystem alteration and reduce conservation risk.

PMID- 21850249
TI  - An institutional mechanism for assortment in an ecology of games.
AB  - Recent research has revived Long's "ecology of games" model to analyze how social
      actors cooperate in the context of multiple political and social games. However,
      there is still a paucity of theoretical work that considers the mechanisms by
      which large-scale cooperation can be promoted in a dynamic institutional
      landscape, in which actors can join new games and leave old ones. This paper
      develops an agent-based model of an ecology of games where agents participate in
      multiple public goods games. In addition to contribution decisions, the agents
      can leave and join different games, and these processes are de-coupled. We show
      that the payoff for cooperation is greater than for defection when limits to the
      number of actors per game ("capacity constraints") structure the population in
      ways that allow cooperators to cluster, independent of any complex individual
      level mechanisms such as reputation or punishment. Our model suggests that
      capacity constraints are one effective mechanism for producing positive
      assortment and increasing cooperation in an ecology of games. The results suggest
      an important trade-off between the inclusiveness of policy processes and
      cooperation: Fully inclusive policy processes reduce the chances of cooperation.

PMID- 21850250
TI  - Adverse events following pandemic A (H1N1) 2009 monovalent vaccines in pregnant
      women--Taiwan, November 2009-August 2010.
AB  - BACKGROUND: During the 2009 H1N1 pandemic, pregnant women were prioritized to
      receive the unadjuvanted or MF59(r)-adjuvanted pandemic A (H1N1) 2009 monovalent
      vaccines ("2009 H1N1 vaccines") in Taiwan regardless of stage of pregnancy.
      Monitoring adverse events following 2009 H1N1 vaccination in pregnant women was a
      priority for the mass immunization campaign beginning November 2009.
      METHODS/FINDINGS: We characterized reports to the national passive surveillance
      from November 2009 through August 2010 involving adverse events following 2009
      H1N1 vaccines among pregnant women. Reports from the passive surveillance were
      matched to a large-linked database on a unique identifier, date of vaccination,
      and date of diagnosis in a capture-recapture analysis to estimate the true number
      of spontaneous abortion after 2009 H1N1 vaccination. We verified 16 spontaneous
      abortions, 11 stillbirths, 4 neonatal deaths, 4 nonpregnancy-specific adverse
      events, and 2 inadvertent immunizations in recipients who were unaware of
      pregnancy at time of vaccination. The Chapman capture-recapture estimator of true
      number of spontaneous abortion after 2009 H1N1 vaccination was 329 (95%
      confidence interval [CI] 196-553). Of the 14,474 pregnant women who received the
      2009 H1N1 vaccines, the estimated risk of spontaneous abortion was 2.3 (95% CI,
      1.4-3.8) per 100 pregnancies, compared with a local background rate of 12.8 (95%
      CI, 12.8-12.9) per 100 pregnancies. CONCLUSIONS: The passive surveillance
      provided rapid initial assessment of adverse events after 2009 H1N1 vaccination
      among pregnant women. Its findings were reassuring for the safety of 2009 H1N1
      vaccines in pregnancy.

PMID- 21850251
TI  - CAR modulates E-cadherin dynamics in the presence of adenovirus type 5.
AB  - Adenovirus (Ad) serotype 5 (Ad5) fiber competitively binds to the coxsackievirus
      and Ad receptor (CAR) to attach Ad5 to target cells and also disrupts cell
      junctions and facilitates virus escape at a late stage in Ad5 infection. Here we
      demonstrate that paracellular permeability in MCF7 and CAR overexpressing MCF7
      (FLCARMCF7) cells is increased within minutes following the addition of Ad5 to
      cells. This is brought about, at least in part, by altering the molecular
      dynamics of E-cadherin, a key component of the cell-cell adhesion complex. We
      also demonstrate that the increase in E-cadherin mobility is constitutively
      altered by the presence of CAR at FLCARMCF7 cell junctions. As increased
      paracellular permeability was observed early after the addition of Ad5 to cells,
      we postulate that this may represent a mechanism by which Ad5 could disrupt cell
      junctions to facilitate further access to its cell receptors.

PMID- 21850252
TI  - Transmission and control of African horse sickness in The Netherlands: a model
      analysis.
AB  - African horse sickness (AHS) is an equine viral disease that is spread by
      Culicoides spp. Since the closely related disease bluetongue established itself
      in The Netherlands in 2006, AHS is considered a potential threat for the Dutch
      horse population. A vector-host model that incorporates the current knowledge of
      the infection biology is used to explore the effect of different parameters on
      whether and how the disease will spread, and to assess the effect of control
      measures. The time of introduction is an important determinant whether and how
      the disease will spread, depending on temperature and vector season. Given an
      introduction in the most favourable and constant circumstances, our results
      identify the vector-to-host ratio as the most important factor, because of its
      high variability over the country. Furthermore, a higher temperature accelerates
      the epidemic, while a higher horse density increases the extent of the epidemic.
      Due to the short infectious period in horses, the obvious clinical signs and the
      presence of non-susceptible hosts, AHS is expected to invade and spread less
      easily than bluetongue. Moreover, detection is presumed to be earlier, which
      allows control measures to be targeted towards elimination of infection sources.
      We argue that recommended control measures are euthanasia of infected horses with
      severe clinical signs and vector control in infected herds, protecting horses
      from midge bites in neighbouring herds, and (prioritized) vaccination of herds
      farther away, provided that transport regulations are strictly applied. The
      largest lack of knowledge is the competence and host preference of the different
      Culicoides species present in temperate regions.

PMID- 21850253
TI  - Hyperphosphorylation as a defense mechanism to reduce TDP-43 aggregation.
AB  - Several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS)
      and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are
      characterized by inclusion bodies formed by TDP-43 (TDP). We established cell and
      transgenic Drosophila models expressing TDP carboxyl terminal fragment (ND251 and
      ND207), which developed aggregates recapitulating important features of TDP
      inclusions in ALS/FTLD-U, including hyperphosphorylation at previously reported
      serine(403,404,409,410) residues, polyubiquitination and colocalization with
      optineurin. These models were used to address the pathogenic role of
      hyperphosphorylation in ALS/FTLD-U. We demonstrated that hyperphosphorylation and
      ubiquitination occurred temporally later than aggregation in cells. Expression of
      CK2alpha which phosphorylated TDP decreased the aggregation propensity of ND251
      or ND207; this effect could be blocked by CK2 inhibitor DMAT. Mutation of
      serines(379,403,404,409,410) to alanines (S5A) to eliminate phosphorylation
      increased the aggregation propensity and number of aggregates of TDP, but
      mutation to aspartic acids (S5D) or glutamic acids (S5E) to simulate
      hyperphosphorylation had the opposite effect. Functionally, ND251 or ND207
      aggregates decreased the number of neurites of Neuro2a cells induced by retinoic
      acid or number of cells by MTT assay. S5A mutation aggravated, but S5E mutation
      alleviated these cytotoxic effects of aggregates. Finally, ND251 or ND251S5A
      developed aggregates in neurons, and salivary gland of transgenic Drosophila, but
      ND251S5E did not. Taken together, our data indicate that hyperphosphorylation may
      represent a compensatory defense mechanism to stop or prevent pathogenic TDP from
      aggregation. Therefore, enhancement of phosphorylation may serve as an effective
      therapeutic strategy against ALS/FTLD-U.

PMID- 21850254
TI  - Development and validation of a new method to measure walking speed in free
      living environments using the actibelt(r) platform.
AB  - Walking speed is a fundamental indicator for human well-being. In a clinical
      setting, walking speed is typically measured by means of walking tests using
      different protocols. However, walking speed obtained in this way is unlikely to
      be representative of the conditions in a free-living environment. Recently,
      mobile accelerometry has opened up the possibility to extract walking speed from
      long-time observations in free-living individuals, but the validity of these
      measurements needs to be determined. In this investigation, we have developed
      algorithms for walking speed prediction based on 3D accelerometry data
      (actibelt(r)) and created a framework using a standardized data set with gold
      standard annotations to facilitate the validation and comparison of these
      algorithms. For this purpose 17 healthy subjects operated a newly developed
      mobile gold standard while walking/running on an indoor track. Subsequently, the
      validity of 12 candidate algorithms for walking speed prediction ranging from
      well-known simple approaches like combining step length with frequency to more
      sophisticated algorithms such as linear and non-linear models was assessed using
      statistical measures. As a result, a novel algorithm employing support vector
      regression was found to perform best with a concordance correlation coefficient
      of 0.93 (95%CI 0.92-0.94) and a coverage probability CP1 of 0.46 (95%CI 0.12
      0.70) for a deviation of 0.1 m/s (CP2 0.78, CP3 0.94) when compared to the mobile
      gold standard while walking indoors. A smaller outdoor experiment confirmed those
      results with even better coverage probability. We conclude that walking speed
      thus obtained has the potential to help establish walking speed in free-living
      environments as a patient-oriented outcome measure.

PMID- 21850255
TI  - Peptide ligands incorporated into the threefold spike capsid domain to re-direct
      gene transduction of AAV8 and AAV9 in vivo.
AB  - Efficiency and specificity of viral vectors are vital issues in gene therapy.
      Insertion of peptide ligands into the adeno-associated viral (AAV) capsid at
      receptor binding sites can re-target AAV2-derived vectors to alternative cell
      types. Also, the use of serotypes AAV8 and -9 is more efficient than AAV2 for
      gene transfer to certain tissues in vivo. Consequently, re-targeting of these
      serotypes by ligand insertion could be a promising approach but has not been
      explored so far. Here, we generated AAV8 and -9 vectors displaying peptides in
      the threefold spike capsid domain. These peptides had been selected from peptide
      libraries displayed on capsids of AAV serotype 2 to optimize systemic gene
      delivery to murine lung tissue and to breast cancer tissue in PymT transgenic
      mice (PymT). Such peptide insertions at position 590 of the AAV8 capsid and
      position 589 of the AAV9 capsid changed the transduction properties of both
      serotypes. However, both peptides inserted in AAV8 did not result in the same
      changes of tissue tropism as they did in AAV2. While the AAV2 peptides selected
      on murine lung tissue did not alter tropism of serotypes 8 and -9, insertion of
      the AAV2-derived peptide selected on breast cancer tissue augmented tumor gene
      delivery in both serotypes. Further, this peptide mediated a strong but
      unspecific in vivo gene transfer for AAV8 and abrogated transduction of various
      control tissues for AAV9. Our findings indicate that peptide insertion into
      defined sites of AAV8 and -9 capsids can change and improve their efficiency and
      specificity compared to their wild type variants and to AAV2, making these
      insertion sites attractive for the generation of novel targeted vectors in these
      serotypes.

PMID- 21850256
TI  - Particulate matter exposure exacerbates high glucose-induced cardiomyocyte
      dysfunction through ROS generation.
AB  - Diabetes mellitus and fine particulate matter from diesel exhaust (DEP) are both
      important contributors to the development of cardiovascular disease (CVD).
      Diabetes mellitus is a progressive disease with a high mortality rate in patients
      suffering from CVD, resulting in diabetic cardiomyopathy. Elevated DEP levels in
      the air are attributed to the development of various CVDs, presumably since fine
      DEP (<2.5 um in diameter) can be inhaled and gain access to the circulatory
      system. However, mechanisms defining how DEP affects diabetic or control
      cardiomyocyte function remain poorly understood. The purpose of the present study
      was to evaluate cardiomyocyte function and reactive oxygen species (ROS)
      generation in isolated rat ventricular myocytes exposed overnight to fine DEP
      (0.1 ug/ml), and/or high glucose (HG, 25.5 mM). Our hypothesis was that DEP
      exposure exacerbates contractile dysfunction via ROS generation in cardiomyocytes
      exposed to HG. Ventricular myocytes were isolated from male adult Sprague-Dawley
      rats cultured overnight and sarcomeric contractile properties were evaluated,
      including: peak shortening normalized to baseline (PS), time-to-90% shortening
      (TPS(90)), time-to-90% relengthening (TR(90)) and maximal velocities of
      shortening/relengthening (+/-dL/dt), using an IonOptix field-stimulator system.
      ROS generation was determined using hydroethidine/ethidium confocal microscopy.
      We found that DEP exposure significantly increased TR(90), decreased PS and +/
      dL/dt, and enhanced intracellular ROS generation in myocytes exposed to HG.
      Further studies indicated that co-culture with antioxidants (0.25 mM Tiron and
      0.5 mM N-Acetyl-L-cysteine) completely restored contractile function in DEP, HG
      and HG+DEP-treated myocytes. ROS generation was blocked in HG-treated cells with
      mitochondrial inhibition, while ROS generation was blocked in DEP-treated cells
      with NADPH oxidase inhibition. Our results suggest that DEP exacerbates
      myocardial dysfunction in isolated cardiomyocytes exposed to HG-containing media,
      which is potentially mediated by various ROS generation pathways.

PMID- 21850257
TI  - Cross-reactivity of anthrax and C2 toxin: protective antigen promotes the uptake
      of botulinum C2I toxin into human endothelial cells.
AB  - Binary toxins are among the most potent bacterial protein toxins performing a
      cooperative mode of translocation and exhibit fatal enzymatic activities in
      eukaryotic cells. Anthrax and C2 toxin are the most prominent examples for the
      AB(7/8) type of toxins. The B subunits bind both host cell receptors and the
      enzymatic A polypeptides to trigger their internalization and translocation into
      the host cell cytosol. C2 toxin is composed of an actin ADP-ribosyltransferase
      (C2I) and C2II binding subunits. Anthrax toxin is composed of adenylate cyclase
      (EF) and MAPKK protease (LF) enzymatic components associated to protective
      antigen (PA) binding subunit. The binding and translocation components anthrax
      protective antigen (PA(63)) and C2II of C2 toxin share a sequence homology of
      about 35%, suggesting that they might substitute for each other. Here we show by
      conducting in vitro measurements that PA(63) binds C2I and that C2II can bind
      both EF and LF. Anthrax edema factor (EF) and lethal factor (LF) have higher
      affinities to bind to channels formed by C2II than C2 toxin's C2I binds to
      anthrax protective antigen (PA(63)). Furthermore, we could demonstrate that PA in
      high concentration has the ability to transport the enzymatic moiety C2I into
      target cells, causing actin modification and cell rounding. In contrast, C2II
      does not show significant capacity to promote cell intoxication by EF and LF.
      Together, our data unveiled the remarkable flexibility of PA in promoting C2I
      heterologous polypeptide translocation into cells.

PMID- 21850258
TI  - Genetic liability to disability pension in women and men: a prospective
      population-based twin study.
AB  - BACKGROUND: Previous studies of risk factors for disability pension (DP) have
      mainly focused on psychosocial, or environmental, factors, while the relative
      importance of genetic effects has been less studied. Sex differences in
      biological mechanisms have not been investigated at all. METHODS: The study
      sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs,
      born 1928-1958, who were followed during 1993-2008. Data on DP, including
      diagnoses, were obtained from the National Social Insurance Agency. Within-pair
      similarity in liability to DP was assessed by calculating intraclass
      correlations. Genetic and environmental influences on liability to DP were
      estimated by applying discrete-time frailty modeling. RESULTS: During follow-up,
      7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass
      correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed
      pairs were more similar than opposite-sexed pairs. The best-fitting model
      indicated that genetic factors contributed 49% (95% CI: 39-59) to the variance in
      DP due to mental diagnoses, 35% (95% CI: 29-41) due to musculoskeletal diagnoses,
      and 27% (95% CI: 20-33) due to all other diagnoses. In both sexes, genetic
      effects common to all ages explained one-third, whereas age-specific factors
      almost two-thirds, of the total variance in liability to DP irrespective of
      diagnosis. Sex differences in liability to DP were indicated, in that partly
      different sets of genes were found to operate in women and men, even though the
      magnitude of genetic variance explained was equal for both sexes. CONCLUSIONS:
      The findings of the study suggest that genetic effects are important for
      liability to DP due to different diagnoses. Moreover, genetic contributions to
      liability to DP tend to differ between women and men, even though the overall
      relative contribution of genetic influences does not differ by sex. Hence, the
      pathways leading to DP might differ between women and men.

PMID- 21850259
TI  - Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected
      with simian immunodeficiency virus: a nonhuman primate AIDS model.
AB  - BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs) infected with
      simian immunodeficiency virus (SIV) have been used for many years to evaluate the
      efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such
      a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL
      FINDINGS: By randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC
      class I alleles into 3 groups (50 animals per group) challenged with intrarectal
      (i.r.) SIVmac239, intravenous (i.v.) SIVmac239, or i.v. SIVmac251, we evaluated
      variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs
      became seropositive for SIV during 1-2 weeks. Plasma viral load (VL) peaked at
      weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL
      was 30 fold higher in SIVmac239 (i.r. or i.v.)-infected than in SIVmac251 (i.v.)
      infected animals. This difference in plasma VL increased overtime (>100 fold as
      from week 68). The rates of progression to AIDS or death were more rapid in
      SIVmac239 (i.r. or i.v.)-infected than in SIVmac251 (i.v.)-infected animals. No
      significant difference in bio-clinical endpoints was observed in animals
      challenged with i.r. or i.v. SIVmac239. The variability (standard deviation) in
      peak/set-point VL was nearly one-half lower in animals infected with SIVmac239
      (i.r. or i.v.) than in those infected with SIVmac251 (i.v.), allowing that the
      same treatment-related difference can be detected with one-half fewer animals
      using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results
      provide solid estimates of variability in bio-clinical endpoints needed when
      designing studies using the Ch RhM SIV model and contribute to the improving
      quality and standardization of preclinical studies.

PMID- 21850260
TI  - HIV envelope gp120 activates LFA-1 on CD4 T-lymphocytes and increases cell
      susceptibility to LFA-1-targeting leukotoxin (LtxA).
AB  - The cellular adhesion molecule LFA-1 and its ICAM-1 ligand play an important role
      in promoting HIV-1 infectivity and transmission. These molecules are present on
      the envelope of HIV-1 virions and are integral components of the HIV virological
      synapse. However, cellular activation is required to convert LFA-1 to the active
      conformation that has high affinity binding for ICAM-1. This study evaluates
      whether such activation can be induced by HIV itself. The data show that HIV-1
      gp120 was sufficient to trigger LFA-1 activation in fully quiescent naive CD4 T
      cells in a CD4-dependent manner, and these CD4 T cells became more susceptible to
      killing by LtxA, a bacterial leukotoxin that preferentially targets leukocytes
      expressing high levels of the active LFA-1. Moreover, virus p24-expressing CD4 T
      cells in the peripheral blood of HIV-infected subjects were found to have higher
      levels of surface LFA-1, and LtxA treatment led to significant reduction of the
      viral DNA burden. These results demonstrate for the first time the ability of HIV
      to directly induce LFA-1 activation on CD4 T cells. Although LFA-1 activation may
      enhance HIV infectivity and transmission, it also renders the cells more
      susceptible to an LFA-1-targeting bacterial toxin, which may be harnessed as a
      novel therapeutic strategy to deplete virus reservoir in HIV-infected
      individuals.

PMID- 21850261
TI  - Microencapsulation technology: a powerful tool for integrating expansion and
      cryopreservation of human embryonic stem cells.
AB  - The successful implementation of human embryonic stem cells (hESCs)-based
      technologies requires the production of relevant numbers of well-characterized
      cells and their efficient long-term storage. In this study, cells were
      microencapsulated in alginate to develop an integrated bioprocess for expansion
      and cryopreservation of pluripotent hESCs. Different three-dimensional (3D)
      culture strategies were evaluated and compared, specifically, microencapsulation
      of hESCs as: i) single cells, ii) aggregates and iii) immobilized on
      microcarriers. In order to establish a scalable bioprocess, hESC-microcapsules
      were cultured in stirred tank bioreactors.The combination of microencapsulation
      and microcarrier technology resulted in a highly efficient protocol for the
      production and storage of pluripotent hESCs. This strategy ensured high expansion
      ratios (an approximately twenty-fold increase in cell concentration) and high
      cell recovery yields (>70%) after cryopreservation. When compared with non
      encapsulated cells, cell survival post-thawing demonstrated a three-fold
      improvement without compromising hESC characteristics.Microencapsulation also
      improved the culture of hESC aggregates by protecting cells from hydrodynamic
      shear stress, controlling aggregate size and maintaining cell pluripotency for
      two weeks.This work establishes that microencapsulation technology may prove a
      powerful tool for integrating the expansion and cryopreservation of pluripotent
      hESCs. The 3D culture strategy developed herein represents a significant
      breakthrough towards the implementation of hESCs in clinical and industrial
      applications.

PMID- 21850262
TI  - Design considerations for massively parallel sequencing studies of complex human
      disease.
AB  - Massively Parallel Sequencing (MPS) allows sequencing of entire exomes and
      genomes to now be done at reasonable cost, and its utility for identifying genes
      responsible for rare Mendelian disorders has been demonstrated. However, for a
      complex disease, study designs need to accommodate substantial degrees of locus,
      allelic, and phenotypic heterogeneity, as well as complex relationships between
      genotype and phenotype. Such considerations include careful selection of samples
      for sequencing and a well-developed strategy for identifying the few "true"
      disease susceptibility genes from among the many irrelevant genes that will be
      found to harbor rare variants. To examine these issues we have performed
      simulation-based analyses in order to compare several strategies for MPS
      sequencing in complex disease. Factors examined include genetic architecture,
      sample size, number and relationship of individuals selected for sequencing, and
      a variety of filters based on variant type, multiple observations of genes and
      concordance of genetic variants within pedigrees. A two-stage design was assumed
      where genes from the MPS analysis of high-risk families are evaluated in a
      secondary screening phase of a larger set of probands with more modest family
      histories. Designs were evaluated using a cost function that assumes the cost of
      sequencing the whole exome is 400 times that of sequencing a single candidate
      gene. Results indicate that while requiring variants to be identified in multiple
      pedigrees and/or in multiple individuals in the same pedigree are effective
      strategies for reducing false positives, there is a danger of over-filtering so
      that most true susceptibility genes are missed. In most cases, sequencing more
      than two individuals per pedigree results in reduced power without any benefit in
      terms of reduced overall cost. Further, our results suggest that although no
      single strategy is optimal, simulations can provide important guidelines for
      study design.

PMID- 21850263
TI  - Multifunctionality and diversity in bacterial biofilms.
AB  - Bacteria are highly diverse and drive a bulk of ecosystem processes. Analysis of
      relationships between diversity and single specific ecosystem processes neglects
      the possibility that different species perform multiple functions at the same
      time. The degradation of dissolved organic carbon (DOC) followed by respiration
      is a key bacterial function that is modulated by the availability of DOC and the
      capability to produce extracellular enzymes. In freshwater ecosystems, biofilms
      are metabolic hotspots and major sites of DOC degradation. We manipulated the
      diversity of biofilm forming communities which were fed with DOC differing in
      availability. We characterized community composition using molecular
      fingerprinting (T-RFLP) and measured functioning as oxygen consumption rates, the
      conversion of DOC in the medium, bacterial abundance and the activities of five
      specific enzymes. Based on assays of the extracellular enzyme activity, we
      calculated how the likelihood of sustaining multiple functions was affected by
      reduced diversity. Carbon source and biofilm age were strong drivers of community
      functioning, and we demonstrate how the likelihood of sustaining
      multifunctionality decreases with decreasing diversity.

PMID- 21850264
TI  - A maternal influence on Reading the mind in the Eyes mediated by executive
      function: differential parental influences on full and half-siblings.
AB  - BACKGROUND: Parent-of-origin effects have been found to influence the mammalian
      brain and cognition and have been specifically implicated in the development of
      human social cognition and theory of mind. The experimental design in this study
      was developed to detect parent-of-origin effects on theory of mind, as measured
      by the 'Reading the mind in the eyes' (Eyes) task. Eyes scores were also entered
      into a principal components analysis with measures of empathy, social skills and
      executive function, in order to determine what aspect of theory of mind Eyes is
      measuring. METHODOLOGY/PRINCIPAL FINDINGS: Maternal and paternal influences on
      Eyes scores were compared using correlations between pairs of full (70 pairs),
      maternal (25 pairs) and paternal siblings (15 pairs). Structural equation
      modelling supported a maternal influence on Eyes scores over the normal range but
      not low-scoring outliers, and also a sex-specific influence on males acting to
      decrease male Eyes scores. It was not possible to differentiate between genetic
      and environmental influences in this particular sample because maternal siblings
      tended to be raised together while paternal siblings were raised apart. The
      principal components analysis found Eyes was associated with measures of
      executive function, principally behavioural inhibition and attention, rather than
      empathy or social skills. CONCLUSIONS/SIGNIFICANCE: In conclusion, the results
      suggest a maternal influence on Eye scores in the normal range and a sex-specific
      influence acting to reduce scores in males. This influence may act via aspects of
      executive function such as behavioural inhibition and attention. There may be
      different influences acting to produce the lowest Eyes scores which implies that
      the heratibility and/or maternal influence on poor theory of mind skills may be
      qualitatively different to the influence on the normal range.

PMID- 21850265
TI  - Differing lectin binding profiles among human embryonic stem cells and
      derivatives aid in the isolation of neural progenitor cells.
AB  - Human embryonic stem cells (hESCs) and their differentiated progeny allow for
      investigation of important changes/events during normal embryonic development.
      Currently most of the research is focused on proteinacous changes occurring as a
      result of differentiation of stem cells and little is known about changes in cell
      surface glycosylation patterns. Identification of cell lineage specific glycans
      can help in understanding their role in maintenance, proliferation and
      differentiation. Furthermore, these glycans can serve as markers for isolation of
      homogenous populations of cells. Using a panel of eight biotinylated lectins, the
      glycan expression of hESCs, hESCs-derived human neural progenitors (hNP) cells,
      and hESCs-derived mesenchymal progenitor (hMP) cells was investigated. Our goal
      was to identify glycans that are unique for hNP cells and use the corresponding
      lectins for cell isolation. Flow cytometry and immunocytochemistry were used to
      determine expression and localization of glycans, respectively, in each cell
      type. These results show that the glycan expression changes upon differentiation
      of hESCs and is different for neural and mesenchymal lineage. For example,
      binding of PHA-L lectin is low in hESCs (14+/-4.4%) but significantly higher in
      differentiated hNP cells (99+/-0.4%) and hMP cells (90+/-3%). Three lectins: VVA,
      DBA and LTL have low binding in hESCs and hMP cells, but significantly higher
      binding in hNP cells. Finally, VVA lectin binding was used to isolate hNP cells
      from a mixed population of hESCs, hNP cells and hMP cells. This is the first
      report that compares glycan expression across these human stem cell lineages and
      identifies significant differences. Also, this is the first study that uses VVA
      lectin for isolation for human neural progenitor cells.

PMID- 21850266
TI  - The interaction of LFA-1 on mononuclear cells and ICAM-1 on tubular epithelial
      cells accelerates TGF-beta1-induced renal epithelial-mesenchymal transition.
AB  - The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has
      pivotal roles in the development of renal fibrosis. Although the interaction of
      lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand,
      intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most
      inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be
      clarified. In the present study, we investigated the effect of the interaction of
      LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells
      after stimulation with TGF-beta(1) on the EMT of RTECs. ICAM-1 was highly
      expressed in HK-2 cells. After TGF-beta(1) stimulation, the chemokines CCL3 and
      CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre
      stimulated with TGF-beta(1) (0.1 ng/ml) (HK-2-TGF-beta(1) (0.1)), the expression
      of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression
      did not change. The expression of the active form of LFA-1 on PBMCs did not
      increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-beta(1)
      (0.1). The expression of epithelial cell junction markers (E-cadherin and
      occludin) further decreased and that of mesenchymal markers (vimentin and
      fibronectin) further increased in HK-2-TGF-beta(1) (0.1) after co-culture with
      PBMCs for 24 hrs (HK-2-TGF-beta(1) (0.1)-PBMCs). The phosphorylation of ERK 1/2
      but not smad2 and smad3 increased in HK-2-TGF-beta(1) (0.1)-PBMCs. The snail and
      slug signaling did not increase HK-2-TGF-beta(1) (0.1)-PBMCs. Although the
      migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml)
      and long-term (72-96 hrs) TGF-beta(1) stimulation increased, that of HK-2-TGF
      beta(1) (0.1)-PBMCs did not increase. These results suggested that HK-2 cells
      stimulated with TGF-beta(1) induced conformational activation of LFA-1 on PBMCs
      by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on
      HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells
      induced by TGF-beta(1).

PMID- 21850267
TI  - Gas6 downregulation impaired cytoplasmic maturation and pronuclear formation
      independent to the MPF activity.
AB  - Previously, we found that the growth arrest-specific gene 6 (Gas6) is more highly
      expressed in germinal vesicle (GV) oocytes than in metaphase II (MII) oocytes
      using annealing control primer (ACP)-PCR technology. The current study was
      undertaken to investigate the role of Gas6 in oocyte maturation and fertilization
      using RNA interference (RNAi). Interestingly, despite the specific and marked
      decrease in Gas6 mRNA and protein expression in GVs after Gas6 RNAi, nuclear
      maturation including spindle structures and chromosome segregation was not
      affected. The only discernible effect induced by Gas6 RNAi was a change in
      maturation promoting factor (MPF) activity. After parthenogenetic activation,
      Gas6 RNAi-treated oocytes at the MII stage had not developed further and arrested
      at MII (90.0%). After stimulation with Sr(2+), Gas6-silenced MII oocytes had
      markedly reduced Ca(2+) oscillation and exhibited no exocytosis of cortical
      granules. In these oocytes, sperm penetration occurred during fertilization but
      not pronucleus (PN) formation. By roscovitine and colcemid treatment, we found
      that the Gas6 knockdown affected cytoplasmic maturation directly, independent to
      the changed MPF activity. These results strongly suggest that 1) the Gas6
      signaling itself is important to the cytoplasmic maturation, but not nuclear
      maturation, and 2) the decreased Gas6 expression and decreased MPF activity
      separately or mutually influence sperm head decondensation and PN formation.

PMID- 21850268
TI  - Repeated labilization-reconsolidation processes strengthen declarative memory in
      humans.
AB  - The idea that memories are immutable after consolidation has been challenged.
      Several reports have shown that after the presentation of a specific reminder,
      reactivated old memories become labile and again susceptible to amnesic agents.
      Such vulnerability diminishes with the progress of time and implies a re
      stabilization phase, usually referred to as reconsolidation. To date, the main
      findings describe the mechanisms associated with the labilization-reconsolidation
      process, but little is known about its functionality from a biological
      standpoint. Indeed, two functions have been proposed. One suggests that
      destabilization of the original memory after the reminder allows the integration
      of new information into the background of the original memory (memory updating),
      and the other suggests that the labilization-reconsolidation process strengthens
      the original memory (memory strengthening). We have previously reported the
      reconsolidation of human declarative memories, demonstrating memory updating in
      the framework of reconsolidation. Here we deal with the strengthening function
      attributed to the reconsolidation process. We triggered labilization
      reconsolidation processes successively by repeated presentations of the proper
      reminder. Participants learned an association between five cue-syllables and
      their respective response-syllables. Twenty-four hours later, the paired
      associate verbal memory was labilized by exposing the subjects to one, two or
      four reminders. The List-memory was evaluated on Day 3 showing that the memory
      was improved when at least a second reminder was presented in the time window of
      the first labilization-reconsolidation process prompted by the earlier reminder.
      However, the improvement effect was revealed on Day 3, only when at least two
      reminders were presented on Day 2 and not as a consequence of only retrieval.
      Therefore, we propose central concepts for the reconsolidation process,
      emphasizing its biological role and the parametrical constrains for this function
      to be operative.

PMID- 21850269
TI  - SLOB, a SLOWPOKE channel binding protein, regulates insulin pathway signaling and
      metabolism in Drosophila.
AB  - There is ample evidence that ion channel modulation by accessory proteins within
      a macromolecular complex can regulate channel activity and thereby impact
      neuronal excitability. However, the downstream consequences of ion channel
      modulation remain largely undetermined. The Drosophila melanogaster large
      conductance calcium-activated potassium channel SLOWPOKE (SLO) undergoes
      modulation via its binding partner SLO-binding protein (SLOB). Regulation of SLO
      by SLOB influences the voltage dependence of SLO activation and modulates
      synaptic transmission. SLO and SLOB are expressed especially prominently in
      median neurosecretory cells (mNSCs) in the pars intercerebralis (PI) region of
      the brain; these cells also express and secrete Drosophila insulin like peptides
      (dILPs). Previously, we found that flies lacking SLOB exhibit increased
      resistance to starvation, and we reasoned that SLOB may regulate aspects of
      insulin signaling and metabolism. Here we investigate the role of SLOB in
      metabolism and find that slob null flies exhibit changes in energy storage and
      insulin pathway signaling. In addition, slob null flies have decreased levels of
      dilp3 and increased levels of takeout, a gene known to be involved in feeding and
      metabolism. Targeted expression of SLOB to mNSCs rescues these alterations in
      gene expression, as well as the metabolic phenotypes. Analysis of fly lines
      mutant for both slob and slo indicate that the effect of SLOB on metabolism and
      gene expression is via SLO. We propose that modulation of SLO by SLOB regulates
      neurotransmission in mNSCs, influencing downstream insulin pathway signaling and
      metabolism.

PMID- 21850270
TI  - Protein X of hepatitis B virus: origin and structure similarity with the central
      domain of DNA glycosylase.
AB  - Orthohepadnavirus (mammalian hosts) and avihepadnavirus (avian hosts) constitute
      the family of Hepadnaviridae and differ by their capability and inability for
      expression of protein X, respectively. Origin and functions of X are unclear. The
      evolutionary analysis at issue of X indicates that present strains of
      orthohepadnavirus started to diverge about 25,000 years ago, simultaneously with
      the onset of avihepadnavirus diversification. These evolutionary events were
      preceded by a much longer period during which orthohepadnavirus developed a
      functional protein X while avihepadnavirus evolved without X. An in silico
      generated 3D-model of orthohepadnaviral X protein displayed considerable
      similarity to the tertiary structure of DNA glycosylases (key enzymes of base
      excision DNA repair pathways). Similarity is confined to the central domain of
      MUG proteins with the typical DNA-binding facilities but without the capability
      of DNA glycosylase enzymatic activity. The hypothetical translation product of a
      vestigial X reading frame in the genome of duck hepadnavirus could also been
      folded into a DNA glycosylase-like 3D-structure. In conclusion, the most recent
      common ancestor of ortho- and avihepadnavirus carried an X sequence with
      orthology to the central domain of DNA glycosylase.

PMID- 21850271
TI  - Genome-wide screening for genes associated with FK506 sensitivity in fission
      yeast.
AB  - We have been studying calcineurin signal transduction pathway in fission yeast
      Schizosaccharomyces pombe (S. pombe) by developing a genetic screen for mutants
      that show hypersensitivity to the immunosuppressive calcineurin inhibitor FK506
      (tacrolimus). In the present study, to identify nonessential genes that are
      functionally related to the calcineurin signaling pathway, we performed a genome
      wide screen of 3004 haploid deletion strains and confirmed 72 deletion strains to
      be FK506 sensitive. These 72 genes are classified into nine functional groups to
      include membrane trafficking (16 genes), signal transduction (10 genes),
      ubiquitination (8 genes), chromatin remodeling (6 genes), cytokinesis (4 genes),
      ribosomal protein (3 genes), RNA binding protein (3 genes), and a variety of
      other known functions (17 genes) or still unknown functions (5 genes) in the
      biological system. In our previous screening of FK506-sensitive mutants we
      isolated several membrane-trafficking mutants showing defective cell wall
      integrity. Here, we further examined the vacuolar fusion, the v-SNARE
      synaptobrevin Syb1 localization, and the sensitivity to the beta-glucan synthase
      inhibitor micafungin in these 72 FK506-sensitive strains. Results showed that 25
      deletion strains exhibited abnormal vacuole fusion, 19 deletion strains exhibited
      Syb1 mislocalization, and 14 deletion strains exhibited both abnormal vacuole
      fusion and Syb1 mislocalization, while 42 deletion strains showed both normal
      vacuole fusion and Syb1 localization. Likewise, 16 deletion strains showed
      sensitivity to micafungin. Altogether, our present study indicates that
      calcineurin mediates a plethora of physiological processes in fission yeast, and
      that calcineurin is extensively involved in cross-talk between signaling
      pathways.

PMID- 21850272
TI  - A role for central nervous growth hormone-releasing hormone signaling in the
      consolidation of declarative memories.
AB  - Contributions of somatotropic hormonal activity to memory functions in humans,
      which are suggested by clinical observations, have not been systematically
      examined. With previous experiments precluding a direct effect of systemic growth
      hormone (GH) on acute memory formation, we assessed the role of central nervous
      somatotropic signaling in declarative memory consolidation. We examined the
      effect of intranasally administered growth hormone releasing-hormone (GHRH; 600
      ug) that has direct access to the brain and suppresses endogenous GHRH via an
      ultra-short negative feedback loop. Twelve healthy young men learned word-pair
      associates at 2030 h and were administered GHRH and placebo, respectively, at
      2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo,
      intranasal GHRH blunted GH release within 3 hours after substance administration
      and reduced the number of correctly recalled word-pairs by ~12% (both P<0.05).
      The impairment of declarative memory consolidation was directly correlated to
      diminished GH concentrations (P<0.05). Procedural memory consolidation as
      examined by the parallel assessment of finger sequence tapping performance was
      not affected by GHRH administration. Our findings indicate that intranasal GHRH,
      by counteracting endogenous GHRH release, impairs hippocampal memory processing.
      They provide first evidence for a critical contribution of central nervous
      somatotropic activity to hippocampus-dependent memory consolidation.

PMID- 21850274
TI  - Remote electrical stimulation by means of implanted rectifiers.
AB  - Miniaturization of active implantable medical devices is currently compromised by
      the available means for electrically powering them. Most common energy supply
      techniques for implants--batteries and inductive couplers--comprise bulky parts
      which, in most cases, are significantly larger than the circuitry they feed.
      Here, for overcoming such miniaturization bottleneck in the case of implants for
      electrical stimulation, it is proposed to make those implants act as rectifiers
      of high frequency bursts supplied by remote electrodes. In this way, low
      frequency currents will be generated locally around the implant and these low
      frequency currents will perform stimulation of excitable tissues whereas the high
      frequency currents will cause only innocuous heating. The present study
      numerically demonstrates that low frequency currents capable of stimulation can
      be produced by a miniature device behaving as a diode when high frequency
      currents, neither capable of thermal damage nor of stimulation, flow through the
      tissue where the device is implanted. Moreover, experimental evidence is provided
      by an in vivo proof of concept model consisting of an anesthetized earthworm in
      which a commercial diode was implanted. With currently available microelectronic
      techniques, very thin stimulation capsules (diameter <500 um) deliverable by
      injection are easily conceivable.

PMID- 21850273
TI  - Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with
      mild pulmonary hypertension induced by monocrotaline.
AB  - The aim of this study was to examine the role of cyclooxygenase-2 (COX-2) and
      downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension
      (PH) using mice with genetically manipulated COX-2 expression. COX-2 knockdown
      (KD) mice, characterized by 80-90% suppression of COX-2, and wild-type (WT)
      control mice were treated weekly with monocrotaline (MCT) over 10 weeks. Mice
      were examined for cardiac hypertrophy/function and right ventricular pressure.
      Lung histopathological analysis was performed and various assays were carried out
      to examine oxidative stress, as well as gene, protein, cytokine and prostanoid
      expression. We found that MCT increased right ventricular systolic and pulmonary
      arterial pressures in comparison to saline-treated mice, with no evidence of
      cardiac remodeling. Gene expression of endothelin receptor A and thromboxane
      synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs.
      Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and
      perivascular edema but activation of inflammatory cells was not predominant under
      the experimental conditions. Heme oxygenase-1 (HO-1) expression and indicators of
      oxidative stress in lungs were significantly increased, especially in COX-2 KD
      MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase
      subunits crucial for superoxide generation, was induced by ~4-fold in both groups
      of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by
      ~85% only in MCT-treated COX-2 KD mice. This study suggests that increased
      oxidative stress-derived endothelial dysfunction, vasoconstriction and mild
      inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of
      early stages of PH when mild hemodynamic changes are evident and not yet
      accompanied by vascular and cardiac remodeling.

PMID- 21850275
TI  - Remodeling of purinergic receptor-mediated Ca2+ signaling as a consequence of EGF
      induced epithelial-mesenchymal transition in breast cancer cells.
AB  - BACKGROUND: The microenvironment plays a pivotal role in tumor cell
      proliferation, survival and migration. Invasive cancer cells face a new set of
      environmental challenges as they breach the basement membrane and colonize
      distant organs during the process of metastasis. Phenotypic switching, such as
      that which occurs during epithelial-mesenchymal transition (EMT), may be
      associated with a remodeling of cell surface receptors and thus altered responses
      to signals from the tumor microenvironment. METHODOLOGY/PRINCIPAL FINDINGS: We
      assessed changes in intracellular Ca(2+) in cells loaded with Fluo-4 AM using a
      fluorometric imaging plate reader (FLIPR(TETRA)) and observed significant changes
      in the potency of ATP (EC(50) 0.175 uM (-EGF) versus 1.731 uM (+EGF), P<0.05),
      and the nature of the ATP-induced Ca(2+) transient, corresponding with a 10-fold
      increase in the mesenchymal marker vimentin (P<0.05). We observed no change in
      the sensitivity to PAR2-mediated Ca(2+) signaling, indicating that these
      alterations are not simply a consequence of changes in global Ca(2+) homeostasis.
      To determine whether changes in ATP-mediated Ca(2+) signaling are preceded by
      alterations in the transcriptional profile of purinergic receptors, we analyzed
      the expression of a panel of P2X ionotropic and P2Y metabotropic purinergic
      receptors using real-time RT-PCR and found significant and specific alterations
      in the suite of ATP-activated purinergic receptors during EGF-induced EMT in
      breast cancer cells. Our studies are the first to show that P2X(5) ionotropic
      receptors are enriched in the mesenchymal phenotype and that silencing of P2X(5)
      leads to a significant reduction (25%, P<0.05) in EGF-induced vimentin protein
      expression. CONCLUSIONS: The acquisition of a new suite of cell surface
      purinergic receptors is a feature of EGF-mediated EMT in MDA-MB-468 breast cancer
      cells. Such changes may impart advantageous phenotypic traits and represent a
      novel mechanism for the targeting of cancer metastasis.

PMID- 21850276
TI  - Effects of shape and size of cobalt ferrite nanostructures on their MRI contrast
      and thermal activation.
AB  - Cobalt ferrite magnetic nanostructures were synthesized via a high temperature
      solution phase method. Spherical nanostructures of various sizes were synthesized
      with the help of seed mediated growth of the nanostructures in organic phase,
      while faceted irregular (FI) cobalt ferrite nanostructures were synthesized via
      the same method but in the presence of a magnetic field. Magnetic properties were
      characterized by SQUID magnetometry, relaxivity measurements and thermal
      activation under RF field, as a function of size and shape. The results show that
      the saturation magnetization of the nanostructures increases with an increase in
      size, and the FI nanostructures exhibit lower saturation magnetization than their
      spherical counterparts. The relaxivity coefficient of cobalt ferrite
      nanostructures increases with increase in size; while FI nanostructures show a
      higher relaxivity coefficient than spherical nanostructures with respect to their
      saturation magnetization. In the case of RF thermal activation, the specific
      absorption rate (SAR) of nanostructures increases with increase in the size. The
      contribution sheds light on the role of size and shape on important magnetic
      properties of the nanostructures in relation to their biomedical applications.

PMID- 21850277
TI  - Risks of Venous Thromboembolism and Mortality Associated With Erythropoiesis
      Stimulating Agents for the Treatment of Cancer-Associated Anemia.

PMID- 21850278
TI  - Attributes of Spirituality Described by Survivors of Sexual Violence.
AB  - This study focuses on what aspects of attributes of spirituality as defined by
      Martsolf and Mickley (1998) are most salient for female and male survivors of
      sexual violence. Content analysis of secondary narrative data, provided by 50
      participants in a study of women's and men's responses to sexual violence, was
      coded to the five attributes of spirituality as defined by Martsolf and Mickley.
      The attribute aspects of connecting with others in spiritual ways and with
      God/higher power were particularly significant. The attribute of transcendence
      was found less important, and the attributes of value, becoming, and meaning were
      not found important. The Martsolf and Mickley framework helped organize narrative
      data for a content analysis of spirituality in survivors of sexual violence.

PMID- 21850279
TI  - Identification of dopamine D2 receptors in gill of Crassostrea virginica.
AB  - The lateral epithelial cells of gill of Crassostrea virginica are innervated by
      dopamine and serotonin nerves that regulate the beating rate of their lateral
      cilia. Terminal release of dopamine slows down the beating rate of the cilia,
      while serotonin release increases the beating rate. Previously, we showed that
      the dopaminergic, but not the serotonergic, mechanism regulating the beating rate
      of the lateral cilia was disrupted by manganese treatments and that this
      disruption was occurring postsynaptically, at the level of the dopamine receptor
      or further downstream in the signal transduction pathway. In humans manganese
      toxicity causes Manganism, a neurological disorder with clinical symptoms similar
      to Parkinson s disease. In this study we utilized pharmacological agents and an
      immunohistofluorescence technique to characterize the dopamine receptor type
      present on the lateral ciliated cells of C. virginica gill. Agonists and
      antagonists to dopamine D1 or dopamine D2 receptors were applied to gill sections
      and beating rates of the lateral cilia were measured by stroboscopic microscopy.
      The D2 agonists and D2 antagonists were effective in mimicking or blocking,
      respectively, the inhibitory actions of dopamine on lateral cilia beating, while
      application of either D1 agonists or D1 antagonists had no significant effect. In
      other experiments we used an epilume fluorescence microscopic fitted with FITC
      filters to view gill sections treated with a primary antibody against D2
      receptors and a FITC-linked secondary antibody. Control gill sections without
      primary antibody exposure were similarly treated and viewed. The D2 antibody
      treated sections showed bright fluorescent receptor-antibody complexes present at
      the lateral ciliated cells and other areas of gill, when compared to controls.
      The results of our immunofluorescence study identify the presence of D2-like
      receptors on the lateral ciliated cells of C. virginica gill and our
      pharmacological results indicate that D2-like receptors are the postsynaptic
      dopamine receptors involved in the cilio-inhibitory response of the lateral
      cilia. The results of this study, when combined with our previous work, further
      suggest that the mechanism of action that underlies the dopaminergic
      neurotoxicity of manganese in gill of C. virginica involves disruption of D2-like
      receptors. C. virginica continues to provide a simple yet good model with which
      to study the physiology of dopaminergic systems as well as the pharmacology of
      drugs affecting biogenic amines.

PMID- 21850280
TI  - Bupropion/naltrexone fixed-dose combination for the treatment of obesity.
AB  - The combination of bupropion and naltrexone is one of the most promising new
      possibilities for the treatment of obesity in an era of increasing prevalence of
      this disease and decreasing options for its pharmacological management. Although
      approved by FDA panel members, it was temporally rejected by the FDA afterwards,
      who demanded more cardiovascular safety data for its commercialization. This
      monograph will focus on the physiology involved in its mechanisms of action and
      results of clinical trials.

PMID- 21850281
TI  - Corifollitropin alfa: a new option to treat female infertility.
AB  - Corifollitropin alfa (Elonva(r)) is the first hybrid follicle-stimulating hormone
      (FSH) molecule with demonstrated sustained follicle-stimulating activity. The
      beta subunit of this molecule contains the carboxy-terminal peptide of human
      chorionic gonadotropin, which alters the pharmacokinetic profile of the molecule.
      It demonstrates a longer circulation half-life and extended time to peak levels
      when compared with recombinant FSH (rFSH). Like rFSH, it lacks luteinizing
      hormone activity and binds specifically to the FSH receptor in vitro. Clinical
      trials show that corifollitropin alfa is able to sustain multiple follicular
      growth for a week, with a similar ovarian response and safety profile as rFSH. A
      single injection of corifollitropin alfa can replace 7 daily injections of rFSH
      during the first week of ovarian stimulation in gonadotropin-releasing hormone
      antagonist protocols. Therefore, corifollitropin alfa addresses the need for a
      simplified treatment approach to lessen the burden of multiple daily injections
      for in vitro fertilization.

PMID- 21850282
TI  - Rasburicase in cancer-related hyperuricemia.
AB  - Tumor lysis syndrome (TLS) is an oncological emergency consisting of several
      metabolic derangements: hyperuricemia, hyperkalemia, hyperphosphatemia and
      hypocalcemia. The rupture of tumor cells in cancer patients can be spontaneous or
      caused by anticancer therapy. Clinical manifestations of TLS include nausea,
      anorexia, arrhythmias or renal failure. Prevention and treatment measures include
      aggressive hydration and concomitant antihyperuricemic therapy. Allopurinol has
      historically been the only available pharmacological option. Rasburicase was
      subsequently approved for the management of elevated plasma uric acid levels in
      adults. This recombinant urate oxidase converts uric acid to allantoin, a more
      soluble byproduct that is safely eliminated by the kidneys. Manufacturer-labeled
      dosing for rasburicase in the pediatric and adult populations is 0.2 mg/kg as a
      daily intravenous (i.v.) infusion for up to 5 days. This review summarizes
      several studies suggesting that flat, single rasburicase dosing regimens may be
      just as effective as weight-based dosing. The optimal, most cost-effective adult
      dose and schedule have yet to be determined.

PMID- 21850283
TI  - Denosumab: an update.
AB  - Denosumab is a fully human monoclonal antibody that inhibits the formation,
      function and survival of osteoclasts, preventing the interaction of tumor
      necrosis factor ligand superfamily member 11 (receptor activator of nuclear
      factor kappa-B ligand, RANKL) with the tumor necrosis factor receptor superfamily
      member 11A (osteoclast differentiation factor receptor, ODFR, receptor activator
      of NF-KB, RANK). This results in a reduction in bone resorption and an increase
      in bone mineral density. In clinical studies, denosumab has been shown to
      decrease the risk for vertebral, hip and nonvertebral fractures in women with
      postmenopausal osteoporosis and the risk for new vertebral fractures in men with
      nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate
      of side effects similar to placebo. A number of clinical trials with denosumab
      are ongoing to demonstrate its value for other indications and to further
      characterize its effects on immunomodulation. Denosumab is a new alternative for
      the prevention and treatment of postmenopausal osteoporosis and a promising agent
      for the treatment of other bone diseases associated with bone loss.

PMID- 21850284
TI  - Interferon alfa and antiretroviral agents: a treatment option for adult T-cell
      leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by
      human T-cell lymphotropic virus type I, and its clinical subtypes are categorized
      into smoldering, chronic, lymphoma and acute types. The standard care for
      patients with the acute, lymphoma and unfavorable chronic types (aggressive ATL)
      consists of intensive chemotherapy with or without subsequent allogeneic
      hematopoietic stem cell transplant, or a combination of interferon alfa and an
      antiretroviral agent, while that for the chronic type without unfavorable
      prognostic factors and the smoldering type (indolent ATL) is watchful waiting.
      Recently, early intervention for indolent ATL employing interferon alfa and an
      antiretroviral agent has been reported to lead to a marked benefit in a
      retrospective study. This modality should be evaluated in larger clinical trials,
      since patients with indolent ATL show a median survival time of as short as 4-5
      years.

PMID- 21850285
TI  - A report from the 164th American Psychiatric Association (May 14-18, 2011 -
      Honolulu, Hawai'i, U.S.A.).
AB  - Although tradition mandates that men should be dressed up in colorless attires,
      why do men visiting Hawai'i run to the first Aloha shop right after landing to
      get a multicolored flowery shirt, with a lei flower or kukui tree nut necklace to
      go with it? The answer to this question could be very complex, but psychiatrists
      attending this year's American Psychiatric Association meeting in the Honolulu
      Convention Center acted in a not dissimilar way by running to the new research
      poster and educational oral sessions of the meeting to learn new colors to paint
      the life of their patients with. And many colors, or at least an ample variety of
      treatment modalities, were discussed throughout the 5-day convention, including,
      notably, a number of innovative drugs with the capability of improving the
      functioning and quality of life of individuals suffering from psychosis,
      depression and a broad range of psychiatric diseases. The following report
      summarizes the main findings from clinical and experimental studies related to
      new psychiatric pharmacotherapies as reported and discussed during the meeting.

PMID- 21850286
TI  - Porous metal membranes for solid-phase extraction of polycyclic aromatic
      hydrocarbons.
AB  - Solid-phase extraction (SPE) is one of the most important techniques for sample
      preparation, purification, concentration and cleanup. Membranes made from
      synthetic organic polymers, cellulose, or glass fibers are used for sample
      pretreatment. In this work, we report that a porous metal membrane, the metal
      filter in HPLC, was used as a novel kind of solid-phase extraction adsorbent
      material. To evaluate the performance of the porous metal membrane for the SPE,
      naphthalene, fluorene, anthracene, phenanthrene, fluoranthene, pyrene, chrysene,
      perylene and benzo(a)pyrene were selected as analytes. Several parameters that
      affected the extraction efficiency such as the extraction time, the concentration
      of NaCl, the extraction temperature and the agitation speed were optimized. The
      experimental result indicates that the porous metal membrane possesses high
      adsorption ability to the tested polycyclic aromatic hydrocarbons (PAHs). Under
      the optimum conditions, the detection limits of the developed method were in the
      range of 0.03-0.082 MUg L(-1) (S/N = 5), and excellent linear correlations
      between peak area and concentration of PAHs were found over the range of 0.1-60
      MUg L(-1). The precisions (RSD) for five replicate extractions of the PAHs from
      sample solutions were in the range of 2.6-5.0%. The recoveries of the PAHs from
      tap water and river water samples spiked with 9 PAHs (20 MUg L(-1) of each
      individual PAH) ranged from 83.0% to 112.5%. The porous metal membrane is
      durable, simple, inexpensive, reproducible and has a high adsorption ability for
      use in SPE of PAHs.

PMID- 21850287
TI  - Layer-by-layer assembly and electrochemical study of a 4-aminothiophenol and
      ytterbium(III) trifluoromethanesulfonate hydrate film on a gold electrode.
AB  - We report on the layer-by-layer assembly and electrochemical properties of 4
      aminothiophenol (P-ATP) and ytterbium(III) trifluoromethanesulfonate hydrate
      (Yb(OTf)(3)) film supported on a gold surface. The fabricated film was
      characterised electrochemically using redox couples Fe(CN)(6)(3-/4-),
      complemented with imaging using atomic force microscopy (AFM). The
      electrocatalytic activity of the prepared electrodes was studied using cyclic and
      differential pulse voltammetries. Electrochemical measurements show that the P
      ATP/Yb(OTf)(3) modified electrode has superb activity towards hydroquinone (HQ)
      oxidation and that there is a significant improvement in the electrode stability
      and reproducibility due to the covalent and coordination reactions.

PMID- 21850288
TI  - Surface-supported 2D heterotriangulene polymers.
AB  - We report on the assembly of tribromo-substituted dimethylmethylene-bridged
      triphenylamine (heterotriangulene) on Ag(111). Depending on activation
      temperature, two-dimensional porous metal-coordination or covalent networks are
      obtained.

PMID- 21850289
TI  - Dinitrogen binding at vanadium in a tris(alkoxide) ligand environment.
AB  - We report the first tris(alkoxide)V(III) complex to bind dinitrogen. Removal of
      THF from V(OR)(3)THF furnishes the highly reactive V(OR)(3) fragment, which binds
      dinitrogen to form [V(OR)(3)](2)(MU-N(2)) in the solid state. Dinitrogen is
      readily released upon dissolution of the complex. Structural and DFT studies are
      consistent with significant activation of N(2) when bound by the vanadium
      tris(alkoxide) platform.

PMID- 21850290
TI  - Rhodium-catalyzed asymmetric addition of arylboroxines to beta-alkoxyacrylate
      esters.
AB  - Asymmetric addition of arylboroxines to beta-alkoxyacrylate esters proceeded in
      the presence of a rhodium complex coordinated with a chiral diene ligand to give
      high yields of beta-alkoxy-beta-arylcarboxylic acid esters with very high
      enantioselectivity.

PMID- 21850291
TI  - Metal-intercalated aromatic hydrocarbons: a new class of carbon-based
      superconductors.
AB  - New carbon-based superconductors are synthesized by intercalating metal atoms
      into the solid-phase hydrocarbons picene and coronene. The highest reported
      superconducting transition temperature, T(c), of a hydrocarbon superconductor is
      18 K for K(3)picene. The physics and chemistry of the hydrocarbon superconductors
      are extensively described for A(x)picene (A: alkali and alkali earth-metal atoms)
      for x = 0-5. The theoretical picture of their electronic structure is also
      reviewed. Future prospects for hydrocarbon superconductors are discussed from the
      viewpoint of combining electronics with condensed-matter physics: modification of
      the physical properties of hydrocarbon solids is explored by building them into a
      field-effect transistor. The features of other carbon-based superconductors are
      compared to clarify the nature of hydrocarbon superconductors.

PMID- 21850292
TI  - Gas-phase reactions of doubly charged actinide cations with alkanes and alkenes-
      probing the chemical activity of 5f electrons from Th to Cm.
AB  - Small alkanes (methane, ethane, propane, n-butane) and alkenes (ethene, propene,
      1-butene) were used to probe the gas-phase reactivity of doubly charged actinide
      cations, An(2+) (An = Th, Pa, U, Np, Pu, Am, Cm), by means of Fourier transform
      ion cyclotron resonance mass spectrometry. Different combinations of doubly and
      singly charged ions were observed as reaction products, comprising species formed
      via metal-ion induced eliminations of small molecules, simple adducts and ions
      resulting from electron, hydride or methide transfer channels. Th(2+), Pa(2+),
      U(2+) and Np(2+) preferentially yielded doubly charged products of hydrocarbon
      activation, while Pu(2+), Am(2+) and Cm(2+) reacted mainly through transfer
      channels. Cm(2+) was also capable of forming doubly charged products with some of
      the hydrocarbons whereas Pu(2+) and Am(2+) were not, these latter two ions
      conversely being the only for which adduct formation was observed. The product
      distributions and the reaction efficiencies are discussed in relation to the
      electronic configurations of the metal ions, the energetics of the reactions and
      similar studies previously performed with doubly charged lanthanide and
      transition metal cations. The conditions for hydrocarbon activation to occur as
      related to the accessibility of electronic configurations with one or two 5f
      and/or 6d unpaired electrons are examined and the possible chemical activity of
      the 5f electrons in these early actinide ions, particularly Pa(2+), is
      considered.

PMID- 21850293
TI  - Synthesis, structure and catalytic activity of alkali metal-free bent-sandwiched
      lanthanide amido complexes with calix[4]-pyrrolyl ligands.
AB  - Simple silylamine elimination reactions of calix[4]-pyrrole
      [R(2)C(C(4)H(2)NH)](4) (R = Me (1), {-(CH(2))(5)-}(0.5) (2)) with 2 equiv. of
      [(Me(3)Si)(2)N](3)Ln(MU-Cl)Li(THF)(3) (Ln = Nd, Sm, Dy) in reflux toluene,
      afforded the novel dinuclear alkali metal-free trivalent lanthanide amido
      complexes (eta(5):eta(1):eta(5):eta(1)-R(8)-calix[4]
      pyrrolyl){LnN(SiMe(3))(2)}(2) (R = Me, Ln = Nd (3), Sm (4), Dy (5); R = {
      (CH(2))(5)-}(0.5), Ln = Nd (6), Sm(7)). The complexes were fully characterized by
      elemental analyses, spectroscopic analyses and single-crystal X-ray analyses. X
      ray diffraction studies showed that each lanthanide metal was supported by
      bispyrrolyl anions in an eta(5) fashion and along with three nitrogen atoms from
      N(SiMe(3))(2) and two other pyrroyl rings in eta(1) modes formed the novel bent
      sandwiched lanthanide amido bridged trivalent lanthanide amido complexes, similar
      to ansa-cyclopentadienyl ligand-supported lanthanide amides with respect to each
      metal center. The catalytic activities of these organolanthanide complexes as
      single component l-lactide polymerization catalysts were studied.

PMID- 21850294
TI  - New europium coordination polymers with efficient energy transfer from conjugated
      tetracarboxylate ligands to Eu3+ ion: syntheses, structures, luminescence and
      magnetic properties.
AB  - Two novel lanthanide coordination polymers, [Eu(2)(EBTC)(DMF)(5)(NO(3))(2)].DMF
      (1) and [Eu(2)(BBTC)(1.5)(CH(3)OH)(2)(H(2)O)(2)].7DMF.HNO(3) (2) (EBTC(4-) = 1,1'
      ethynebenzene-3,3',5,5'-tetracarboxylate; BBTC(4-) = 1,1'-butadiynebenzene
      3,3',5,5'-tetracarboxylate), were successfully synthesized from conjugated
      ligands of EBTC(4-) and BBTC(4-). Although the two tetracarboxylate ligands have
      similar structures, their different rigidity/flexibility results in quite
      different networks upon complexation. Complex 1 has a two-dimensional (2-D)
      layered structure with two crystallographically independent Eu(3+) ions, one in a
      distorted monocapped square-antiprism and the other in a distorted square
      antiprism coordination geometry. Complex 2 exhibits a three-dimensional (3-D)
      porous framework, with one type of Eu(3+) in a distorted square-antiprism and the
      other in a trigondodecahedron environment. Both 1 and 2 emit the intensely red
      characteristic luminescence of Eu(3+) ion at room temperature, with a long
      lifetime of up to 1.3 and 0.7 ms, respectively, during which the ligand emission
      of EBTC(4-)/BBTC(4-) was quenched by the Eu(3+) ion, indicating the existence of
      efficient energy transfer between the conjugated ligand of EBTC(4-)/BBTC(4-) and
      the Eu(3+) ion. Thus, both EBTC(4-) and BBTC(4-) are ideal ligands with an
      "antenna" effect for the Eu(3+) ion. The two complexes show the single-ion
      magnetic behaviors of Eu(3+) with strong spin-orbit coupling interactions even if
      there are shorter distances (5.714 A for 1 versus 4.275 and 5.360 A for 2)
      between the neighboring Eu(3+) ions connected by oxygen atoms of the
      tetracarboxylates.

PMID- 21850295
TI  - Self-assembly between dicarboxylate ions and a binuclear europium complex:
      formation of stable adducts and heterometallic lanthanide complexes.
AB  - A binuclear lanthanide complex consisting of two lanthanide binding domains
      linked by a m-xylyl bridging unit forms very stable 1 : 1 adducts with benzene
      dicarboxylic acids and their derivatives. The complex with isophthalate
      derivatives is particularly stable.

PMID- 21850296
TI  - Catalytic hydrodechlorination of 1,2-dichloroethane using copper nanoparticles
      under reduction conditions of sodium borohydride.
AB  - 1,2-Dichloroethane (1,2-DCA) is a raw material used for the manufacture of vinyl
      chloride monomer (VCM) and therefore has very often been detected in the
      groundwater nearby the VCM manufacturing plant. Zero-valent iron (ZVI) is capable
      of degrading a wide array of highly chlorinated contaminants; however, the
      reactivity of ZVI towards 1,2-DCA is very low. In this study, zero-valent copper
      nanoparticles have been synthesized for effective dechlorination of 1,2-DCA under
      reduction conditions of sodium borohydride. Copper nanoparticles consisted of
      mainly metallic copper (Cu(0)) with small amounts of cuprous oxide (Cu(2)O). They
      have surface areas of about 19.0 m(2) g(-1) and an average diameter of 15 nm.
      Batch experiments were conducted to test the effectiveness of copper
      nanoparticles for 1,2-DCA degradation using sodium borohydride as electron donors
      where the ORP was measured as -1100 mV. More than 80% of 1,2-DCA (30 mg L(-1))
      was rapidly degraded within 2 h in the presence of both copper nanoparticles (2.5
      g L(-1)) and borohydride (25 mM). No reduction of 1,2-DCA was observed when the
      system contained either copper nanoparticles alone or borohydride alone. The
      degradation intermediates included ethane and ethylene accounting for 79% and
      ~1.5% of the 1,2-DCA lost, respectively. Potential environmental applications can
      be achieved by immobilizing copper nanoparticles onto the surface of reducing
      metals to form a reactive bimetallic structure.

PMID- 21850297
TI  - Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem
      cell aggregates.
AB  - Culturing stem cells as free-floating aggregates in suspension facilitates large
      scale production of cells in closed systems, for clinical use. To comply with GMP
      standards, the use of substances such as proteolytic enzymes should be avoided.
      Instead of enzymatic dissociation, the growing cell aggregates may be
      mechanically cut at passage, but available methods are not compatible with large
      scale cell production and hence translation into the clinic becomes a severe
      bottle-neck. We have developed the Biogrid device, which consists of an array of
      micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which
      the microgrid is placed across the central fluid channel. By connecting one side
      of the Biogrid to a syringe or a pump and the other side to the cell culture, the
      culture medium with suspended cell aggregates can be aspirated, forcing the
      aggregates through the microgrid, and ejected back to the cell culture container.
      Large aggregates are thereby dissociated into smaller fragments while small
      aggregates pass through the microgrid unaffected. As proof-of-concept, we
      demonstrate that the Biogrid device can be successfully used for repeated passage
      of human neural stem/progenitor cells cultured as so-called neurospheres, as well
      as for passage of suspension cultures of human embryonic stem cells. We also show
      that human neural stem/progenitor cells tolerate transient pressure changes far
      exceeding those that will occur in a fluidic system incorporating the Biogrid
      microgrids. Thus, by using the Biogrid device it is possible to mechanically
      passage large quantities of cells in suspension cultures in closed fluidic
      systems, without the use of proteolytic enzymes.

PMID- 21850298
TI  - Vapor deposition of cross-linked fluoropolymer barrier coatings onto pre
      assembled microfluidic devices.
AB  - The interior surfaces of pre-assembled poly(dimethylsiloxane) (PDMS) microfluidic
      devices were modified with a cross-linked fluoropolymer barrier coating that
      significantly increased the chemical compatibility of the devices.

PMID- 21850299
TI  - Continuous-flow, palladium-catalysed alkoxycarbonylation reactions using a
      prototype reactor in which it is possible to load gas and heat simultaneously.
AB  - A prototype tube-in-tube reactor in which it is possible to load gas and heat
      simultaneously has been used in a continuous-flow approach to alkoxycarbonylation
      reactions of aryl iodides. In the stainless steel coil, liquid flows on the
      outside of a gas-permeable membrane. The coil can be heated and the temperature
      can be measured accurately via a probe touching the outer steel surface. A range
      of aryl iodides can be transformed to the corresponding esters in excellent
      conversion by reaction at 120  degrees C using 0.5 mol% palladium acetate as the
      catalyst with no additional ligand required. Small-scale optimization and
      substrate screening runs were followed by scale-up.

PMID- 21850301
TI  - Post-modern valence bond theory for strongly correlated electron spins.
AB  - We give a pedagogical overview of our recently introduced electronic-structure
      method, Coupled Cluster Valence Bond (CCVB). We show that CCVB can be viewed as
      an approximation to the accurate, yet very expensive, Spin Coupled Valence Bond
      model (SCVB). Both of these models are intended for use on strongly correlated
      molecular systems, especially when the strong correlations are due to electron
      spin coupling. Using familiar ideas from electronic-structure theory, we provide
      definitions for these strong-correlation concepts. We show that CCVB and SCVB
      generally produce similar results, with more substantial discrepancies occurring
      for systems displaying electronic resonance. We conclude that CCVB is a useful,
      inexpensive alternative to SCVB.

PMID- 21850300
TI  - A facile enantioseparation for amino acids enantiomers using beta-cyclodextrins
      functionalized Fe3O4 nanospheres.
AB  - Herein is presented a strategy for the enantioseparation of amino acids
      enantiomers using beta-CD functionalized Fe(3)O(4) nanospheres, in which beta-CD
      provides the ability to chirally discriminate amino acids enantiomers, while the
      Fe(3)O(4) nanoparticles serve as magnetic separators.

PMID- 21850302
TI  - Electrochemical detection of receptor-mediated endocytosis by scanning
      electrochemical microscopy.
AB  - We report a scanning electrochemical microscopy (SECM)-based receptor-mediated
      endocytosis detection method. Epidermal growth factor receptor (EGFR), which is
      one of the key membrane proteins associated with cancer, was used as a model for
      receptor-mediated endocytosis. EGFR molecules on the outer cell membrane were
      detected by SECM by using alkaline phosphatase (ALP) as a labeling enzyme. Since
      SECM detected the ALP activity on the outer membrane, the procedure helped
      discriminate the EGFR on the outer membrane from the intracellular EGFR involved
      in endocytosis. SECM showed a marked decrease in the current responses generated
      due to ALP activity by 93% on addition of the epidermal growth factor, indicating
      clearly that EGF triggered the endocytosis, which led to the withdrawal of most
      EGFRs from the outer membrane.

PMID- 21850303
TI  - Synthesis of cuprous oxide nanocomposite electrodes by room-temperature chemical
      partial reduction.
AB  - We demonstrate a template-free synthetic approach for the preparation of a highly
      conductive Cu/Cu(2)O nanocomposite electrode by a chemical reduction process.
      Cu(2)O octahedra were prepared through chemical dehydrogenation of as-synthesized
      Cu(OH)(2) nanowire precursors. To provide a sufficiently electron-conducting
      network, the Cu(2)O particles were transformed into Cu/Cu(2)O nanocomposites by
      an intentional reduction process. The Cu/Cu(2)O nanocomposite electrodes showed
      enhanced cycling performance compared to Cu(2)O particles. Furthermore, their
      rate capabilities were superior to those of their mechanically mixed Cu/Cu(2)O
      counterparts. This enhanced electrochemical performance of the hybrid Cu/Cu(2)O
      nanocomposites was ascribed to the formation of homogeneous nanostructures,
      offering an efficient electron-transport path provided by the presence of highly
      dispersed Cu nanoparticles.

PMID- 21850304
TI  - An X-ray absorption spectroscopic study on mixed conductive
      La0.6Sr0.4Co0.8Fe0.2O(3-delta) cathodes. I. Electrical conductivity and
      electronic structure.
AB  - The electrical conduction mechanism of mixed conductive perovskite oxides,
      La(0.6)Sr(0.4)Co(0.8)Fe(0.2)O(3-delta), for cathode materials of solid oxide fuel
      cells has been investigated from electronic structural changes during oxygen
      vacancy formation. La(0.6)Sr(0.4)Co(0.8)Fe(0.2)O(3-delta) was annealed under
      various oxygen partial pressures p(O(2))s at 1073 K and quenched. Iodometric
      titration indicated that the oxygen nonstoichiometry of
      La(0.6)Sr(0.4)Co(0.8)Fe(0.2)O(3-delta) depended on the annealing p(O(2)), with
      more oxygen vacancies introduced at lower than at higher p(O(2))s. X-Ray
      absorption spectroscopic measurements were performed at the O K-, Co L-, Fe L-,
      Co K-, and Fe K-edges. The valence states of the Co and Fe ions were investigated
      by the X-ray absorption near edge structure (XANES) at the Co and Fe L(III)
      edges. While the Fe average valence was almost constant, the valence of the Co
      ions decreased with oxygen vacancy introduction. The O K-edge XANES spectra
      indicated that electrons were injected into the Co 3d/O 2p hybridization state
      with oxygen vacancy introduction. Both absorption edges at the Co and Fe K-edge
      XANES shifted towards lower energies with oxygen vacancy introduction. The shift
      at the Co K-edge resulted from the decrease in the Co average valence and that at
      the Fe K-edge appeared to be caused by changes in the coordination environment
      around the Fe ions. The total conductivity of La(0.6)Sr(0.4)Co(0.8)Fe(0.2)O(3
      delta) decreased with decreasing p(O(2)), due to a decreasing hole concentration.

PMID- 21850305
TI  - Combined application of a laser ablation-ICP-MS assay for screening and ESI-FTICR
      MS for identification of a Cd-binding protein in Spinacia oleracea L. after
      exposure to Cd.
AB  - We have studied the binding of the toxic element Cd to plant proteins and have
      used for this purpose spinach (Spinacia oleracea L.) plants treated with 50 MUM
      Cd(II) as a model system. Laser ablation ICP-MS has been applied for the
      screening of Cd-binding proteins after separation by native anodal polyacrylamide
      gel electrophoresis (AN-PAGE) and electroblotting onto membranes. The main Cd
      carrying protein band was isolated and investigated by nano-electrospray
      ionization-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry
      after tryptic digestion. By this procedure, the main Cd-binding protein was
      identified as ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). The
      latter enzyme has been discussed in the literature to be affected in its activity
      by oxidative stress induced by Cd. However, in this paper it is demonstrated for
      the first time that RuBisCO directly binds Cd and thus may be directly altered by
      this toxic element. A commercially available protein standard was used to verify
      direct binding of Cd(II) to the protein, even without metabolisation. The
      resulting metal-protein complex was shown to be stable enough to survive AN-PAGE
      separation and electroblotting. By the use of size exclusion chromatography
      coupled with ICP-MS it was demonstrated that the RuBisCO protein standard shows
      similar metal binding properties to Cd. Furthermore, essential elements such as
      Mn(II), Fe(II) and Cu(II), which are known to possibly replace the RuBisCO
      activator Mg(II), were investigated in addition to Zn(II). Again, similar binding
      properties in comparison to the plant protein were observed.

PMID- 21850306
TI  - Diversifying the structural architecture of synthetic oligomers: the hetero
      foldamer approach.
AB  - Conformationally ordered synthetic oligomers, also called "foldamers", have
      attracted considerable attention in recent years owing to their ability to mimic
      the structural architecture of biopolymers and also because of their potential
      applications in biomedical and material science fields. Until recently, the major
      focus in this area has been the development of oligomers featuring a single type
      of monomer building blocks. However, due to the enormous possibility of
      augmenting the conformational space available for oligomer design, the hetero
      foldamer approach has been introduced very recently. This feature article aims to
      describe foldamers with unique structural architectures, exclusively featuring
      heterogeneous backbones (hetero foldamers).

PMID- 21850307
TI  - Electronic and magnetic properties of C-adsorbed graphene: a first-principles
      study.
AB  - Using density functional theory, we consider the adsorption of C on graphene,
      which gives rise to many interesting phenomena. A single-C at the bridge site
      shows a clearly covalent-bond feature with graphene, in which the metallic state
      occurs and a magnetic moment of 0.36 MU(B) was determined. For both-sided
      adsorption, the magnetic moment is remarkably larger than that in one-sided
      adsorption, and increases with concentration up to a coverage of 12.5%. High spin
      polarization obtained at the Fermi level indicates a high degree of passage of
      preferred spin, which is important for developing spin filters.

PMID- 21850308
TI  - Theoretical study on the gas phase reaction of acrylonitrile with a hydroxyl
      radical.
AB  - The mechanism and kinetics of the reaction of acrylonitrile (CH(2)=CHCN) with
      hydroxyl (OH) has been investigated theoretically. This reaction is revealed to
      be one of the most significant loss processes of acrylonitrile. BHandHLYP and M05
      2X methods are employed to obtain initial geometries. The reaction mechanism
      conforms that OH addition to C[double bond, length as m-dash]C double bond or C
      atom of -CN group to form the chemically activated adducts, 1-IM1(HOCH(2)=CHCN),
      2-IM1(CH(2)=HOCHCN), and 3-IM1(CH(2)=CHCOHN) via low barriers, and direct
      hydrogen abstraction paths may also occur. Temperature- and pressure-dependent
      rate constants have been evaluated using the Rice-Ramsperger-Kassel-Marcus
      theory. The calculated rate constants are in good agreement with the experimental
      data. At atmospheric pressure with N(2) as bath gas, 1-IM1(OHCH(2)=CHCN) formed
      by collisional stabilization is the major product in the temperature range of 200
      1200 K. The production of CH(2)CCN and CHCHCN via hydrogen abstractions becomes
      dominant at high temperatures (1200-3000 K).

PMID- 21850309
TI  - The photoinduced isomerization and its implication in the photo-dynamical
      processes in two simple Schiff bases isolated in solid argon.
AB  - Two Schiff bases: 2-(1-(methylimino)methyl)-phenol (SMA) and its
      chlorosubstituted derivative 2-(1-(methylimino)methyl)-6-chlorophenol (SMAC), and
      SMA complexes with water were studied by infrared matrix isolation spectroscopy
      and DFT/B3LYP/6-311G++(2d,2p) quantum chemical calculations. SMA and SMAC bases
      trapped in an argon matrix from the vapor above the liquid and solid samples have
      the most stable enol conformation with intramolecular O-H...N bonding.
      Irradiation (lambda > 320 nm) leads in both bases to a rotational isomerization
      reaction in which the scission of the O-H...N bond occurs and the C(H)NCH(3) and
      OH groups are turned by 180 degrees  around the C-C and C-O bonds, respectively.
      In SMAC a competitive photoreaction channel yields the trans-keto tautomer. The
      identification of the two SMAC photoproducts evidences that in the excited enol
      form of this compound two processes compete with each other: the rotational
      isomerization and intramolecular proton transfer (ESIPT). In the argon matrices
      doped with SMA and H(2)O the SMA-water complexes were identified and
      characterized spectroscopically. Interaction of SMA with one or two water
      molecules does not affect the photochemistry of SMA.

PMID- 21850310
TI  - Relating the current science of ion-defect behavior in ice to a plausible
      mechanism for directional charge transfer during ice particle collisions.
AB  - A melding of modern experimental results descriptive of fundamental ion defect
      properties of ice is presented as a logical basis of a mechanism for the
      preferential transfer of positive charge from large to small colliding ice
      particles. The result may relate to the electrification of storm clouds. It is
      broadly agreed that such localized charge transfer during collision of small
      upwardly mobile ice particles with falling ice granules (i.e., graupel/hail) can
      lead to macroscopic charge separation capable of initiating lightning strikes
      during the expansion stage of a storm cell. Though the larger particles are
      thought to become negatively charged during the collisions neither a generally
      favored charge-exchange agent nor a preferred mechanism for the directional
      particle-to-particle charge transfer exists. Nevertheless, should ionic point
      defects of ice play a key role, the fundamental properties of ice defects
      considered here must apply. They include: (1) above 140 K protons move readily
      within and on the surface of ice while hydroxide ions are orders-of-magnitude
      less mobile, (2) whether generated by dissociation of HCl buried in ice, during
      neat ice particle growth, or at platinum-ice interfaces, interior protons move to
      and apparently collect at the ice-vacuum interface, and (3) proton activity and
      populations are orders-of-magnitude greater at the surface of ice films and free
      standing ice particles than in the interior. From these fundamentals an untested
      argument is developed that within an ensemble of free floating ice particles the
      proton density at the surface is greater for larger particles. This implies a
      plausible proton-based mechanism that is consistent with current concepts of ice
      particle charging through collisions.

PMID- 21850311
TI  - Facile synthesis and electrochemiluminescence application of concave
      trisoctahedral Pd@Au core-shell nanocrystals bound by {331} high-index facets.
AB  - Concave trisoctahedral (TOH) Pd@Au core-shell nanocrystals bound by {331} facets
      have been synthesized for the first time. Pd nanocubes and cetyltrimethylammonium
      chloride were used as the structure-directing cores and capping agents,
      respectively. Their optical and electrocatalytic properties were investigated.

PMID- 21850315
TI  - Impaired TGF-beta signaling and a defect in resolution of inflammation contribute
      to delayed wound healing in a female rat model of type 2 diabetes.
AB  - Wound healing (WH) impairment is a well-documented phenomenon in clinical and
      experimental diabetes. Sex hormones, in addition to a number of signaling
      pathways including transforming growth factor-beta1 (TGF-beta1)/Smads and TNF
      alpha/NF-kappaB in macrophages and fibroblasts, appear to play a cardinal role in
      determining the rate and nature of WH. We hypothesized that a defect in
      resolution of inflammation and an enhancement in TNF-alpha/NF-kappaB activity
      induced by estrogen deficiency contribute to the impairment of TGF-beta signaling
      and delayed WH in diabetes models. Goto-Kakizaki (GK) rats and full thickness
      excisional wounds were used as models for type 2 diabetes (T2D) and WH,
      respectively. Parameters related to the various stages of WH were assessed using
      histomorphometry, western blotting, real-time PCR, immunofluorescence microscopy
      and ELISA-based assays. Retarded re-epithelialization, suppressed angiogenesis,
      delayed wound closure, reduced estrogen level and heightened states of oxidative
      stress were characteristic features of T2D wounds. These abnormalities were
      associated with a defect in resolution of inflammation, shifts in macrophage
      phenotypes, increased beta3-integrin expression, impaired wound TGF-beta1
      signaling (?p-Smad2/?Smad7) and enhanced TNF-alpha/NFkappaB activity. Human/rat
      dermal fibroblasts of T2D, compared to corresponding control values, displayed
      resistance to TGF-beta-mediated responses including cell migration, myofibroblast
      formation and p-Smad2 generation. A pegylated form of soluble TNF receptor-1 (PEG
      sTNF-RI) or estrogen replacement therapy significantly improved re
      epithelialization and wound contraction, enhanced TGFbeta/Smad signaling, and
      polarized the differentiation of macrophages toward an M2 or "alternatively"
      activated phenotype, while limiting secondary inflammatory-mediated injury. Our
      data suggest that reduced estrogen levels and enhanced TNF-alpha/NF-kappaB
      activity delayed WH in T2D by attenuating TGFbeta/Smad signaling and impairing
      the resolution of inflammation; most of these defects were ameliorated with
      estrogen and/or PEG-sTNF-RI therapy.

PMID- 21850316
TI  - Instantaneous derivatization technology for the simultaneous and homogeneous
      detection of multiple double-stranded PCR amplicons.
AB  - Herein we report on the development of instantaneous derivatization technology
      for the homogeneous and simultaneous detection of multiple PCR amplicons specific
      to the Hepatitis B Virus (HBV) by using three carriers: magnetic beads,
      polystyrene beads, and thermo-sensitive poly-N-isopropylacrylamide (PNIP).
      Briefly, PCR amplicons are labeled with digoxin, biotin or FITC via the modified
      up-stream primers respectively. After PCR amplification, the immunoreactions
      occur between a mixture of three target PCR amplicons and three modified carriers
      with anti-digoxin antibody, streptavidin or anti-FITC antibody in a single
      vessel, and then each carrier is separated from the others under different
      conditions based on their physio-chemical attributes. And then direct CL
      detection proceeds via the instantaneous derivatization reaction between
      intrinsic guanine nucleobases and 3,4,5-trimethoxylphenylglyoxal (TMPG). This new
      protocol directly measures the double-stranded DNA and therefore does not require
      a denaturing step, thus offering an enhanced sensitivity due to the absence of
      competitive hybridization, i.e., the detection limit had a 20-fold improvement on
      the conventional PCR measurement. Additionally, by comparison of previous guanine
      based detection formats, this protocol is easy to be used for the detection of
      any guanine containing targets without the use of guanine-free or inosine
      substituted capture probes. Overall, the proposed technique takes the advantages
      of sensitivity, high-speed and cost-effectivity, which provides a promising
      alternative for the analysis of multiple PCR targets in a variety of clinical,
      environmental, and biodefense fields.

PMID- 21850317
TI  - Unexpected golden Ullmann reaction catalyzed by Au nanoparticles supported on
      periodic mesoporous organosilica (PMO).
AB  - We demonstrated an unprecedented example of Ullmann homocoupling reaction of aryl
      iodides over a novel recyclable gold catalyst comprising Au nanoparticles
      supported on a bifunctional periodic mesoporous organosilica (Au@PMO).

PMID- 21850318
TI  - Rhodium-catalyzed direct ortho C-H olefination of phenol derivatives.
AB  - Cationic rhodium complex-catalyzed olefination of phenol derivatives for the
      direct introduction of an alpha,beta-unsaturated ester appendage is described. In
      addition, deuterium labelling and kinetic isotope effect studies were performed
      to probe the reaction mechanism.

PMID- 21850319
TI  - A reactive force field for aqueous-calcium carbonate systems.
AB  - A new reactive force field has been derived that allows the modelling of
      speciation in the aqueous-calcium carbonate system. Using the ReaxFF methodology,
      which has now been implemented in the program GULP, calcium has been simulated as
      a fixed charge di-cation species in both crystalline phases, such as calcite and
      aragonite, as well as in the solution phase. Excluding calcium from the charge
      equilibration process appears to have no adverse effects for the simulation of
      species relevant to the aqueous environment. Based on this model, the speciation
      of carbonic acid, bicarbonate and carbonate have been examined in microsolvated
      conditions, as well as bulk water. When immersed in a droplet of 98 water
      molecules and two hydronium ions, the carbonate ion is rapidly converted to
      bicarbonate, and ultimately carbonic acid, which is formed as the metastable cis
      trans isomer under kinetic control. Both first principles and ReaxFF calculations
      exhibit the same behaviour, but the longer timescale accessible to the latter
      allows the diffusion of the carbonic acid to the surface of the water to be
      observed, where it is more stable at the interface. Calcium carbonate is also
      examined as ion pairs in solution for both CaCO(3)(0)((aq)) and
      CaHCO(3)(+)((aq)), in addition to the (1014) surface in contact with water.

PMID- 21850320
TI  - Atomic structures of the defective SrTiO3 (001) surface.
AB  - Surface structures of defective SrTiO(3) (001) have been studied by using
      scanning probe microscopy and density functional theory calculations. We observed
      several defective surface structures with true atomic resolution under reducing
      ultrahigh vacuum conditions. It is found that all the defects are terminated by
      (001), (100) and (010) microfacets of the TiO(2) plane. We propose microfaceting
      TiO(2) termination with Sr adatom models. The formation of various types of
      defects is driven by the changes of the surface stoichiometry depending on
      surface preparations.

PMID- 21850321
TI  - Electropolymerization of naphthaleneamidinemonoimide-modified poly(thiophene).
AB  - The new polymer presents a p-doping process with anion exchange and its
      electrochemical reduction with cation exchange during potential cycling. Stored
      specific charges of 38 mAh g(-1) for the polymer reduction and 13 mAh g(-1) for
      its oxidation make the material very promising for fast charge/discharge
      batteries or specialised supercapacitors in which the material is also required
      as the anode.

PMID- 21850322
TI  - Conformationally resolved structures of jet-cooled acetaminophen by UV-UV hole
      burning spectroscopy.
AB  - The conformational structures of jet-cooled acetaminophen were investigated in
      the gas phase by resonant 2-photon ionization and UV-UV hole-burning
      spectroscopy. In contrast to the results from a previous study, two nearly
      isoenergetic conformers were distinctly found in a supersonic molecular beam
      expansion and positively identified as the cis and trans isomers of acetaminophen
      by UV-UV hole-burning spectroscopy. The 0-0 bands of the cis and trans isomers
      were found at 33518.7 and 33485.6 cm(-1), respectively. The vibronic bands of the
      two isomers are close-lying and/or partially overlapping due to the small energy
      difference (33 cm(-1)) between the two 0-0 bands. As a consequence, the recorded
      resonant 2-photon ionization spectrum is highly congested in the low excitation
      energy region, which develops continuously into a featureless, broadened spectrum
      in the high energy region.

PMID- 21850323
TI  - Electrospinning of carbon-coated MoO2 nanofibers with enhanced lithium-storage
      properties.
AB  - Novel carbon-coated MoO(2) nanofibers have been fabricated through a controlled
      route based on single-nozzle electrospinning, air stabilization, and
      reduction/carbonization processes. They are composed of both a uniform
      carbonaceous shell of ~3 nm in thickness and a hierarchical core made of primary
      MoO(2) nanocrystal clusters of ~20 nm in size. Importantly, the electrode made of
      such unique carbon-coated MoO(2) nanofibers exhibits a highly reversible capacity
      as high as 762.7 mAh g(-1) over 100 cycles. In contrast to the carbon-free MoO(2)
      particulates, the MoO(2) nanofibers, featuring both nanocrystal clusters and
      carbon coating, reveal a substantial improvement in electrochemical lithium
      storage performances. This might benefit from the synergistic effect of the
      nanohybridization, relieving the volume effect during the repeated lithium
      insertion/extraction reactions and maintaining electrical connective integrity.
      It is expected that the present synthetic strategy can be extended to synthesize
      other nanostructured oxides with carbon coating for important energy storage and
      transfer applications.

PMID- 21850325
TI  - Synthesis and structural characterization of pincer type bicyclic diacyloxy- and
      diazaselenuranes.
AB  - Synthesis and structural characterization of a new class of pincer type bicyclic
      diacyloxy- and diazaselenuranes is reported. The reaction of dimethyl 2-bromo-5
      tert-butylisophthalate (28) with sodium benzeneselenolate affords the
      corresponding monoselenide, dimethyl 5-tert-butyl-2-(phenylselanyl)isophthalate
      (29). Reduction of 29 with LiAlH(4) provides 5-tert-butyl-2-(phenylselanyl)-1,3
      phenylene)dimethanol 31. Oxidation of 29 or its hydrolyzed derivative, 5-tert
      butyl-2-(phenylselanyl)isophthalic acid (30), with H(2)O(2) results in the
      formation of bicyclic diacyloxyselenurane (25). The reaction of 30 with aniline
      using the DCC coupling reaction gives 5-tert-butyl-N(1),N(3)-diphenyl-2
      (phenylselanyl)isophthalamide (38). Reaction of 38 with H(2)O(2) leads to the
      formation of the corresponding bicyclic diazaselenurane (27) via selenoxide
      intermediate 39. Compounds 25, 27, 29 and 31 were characterized by single crystal
      X-ray crystallography. The structural aspects of the pincer type bicyclic
      chalcogenuranes are investigated using experimental and computational studies and
      compared with the related systems.

PMID- 21850324
TI  - Natural abundance solid-state 67Zn NMR characterization of microporous zinc
      phosphites and zinc phosphates at ultrahigh magnetic field.
AB  - Zinc-phosphite and -phosphate based microporous materials are crystalline open
      framework materials with potential industrial applications. Although (31)P MAS
      NMR has been used for characterization of these materials, the local environments
      around zinc centres have never been directly probed by solid-state NMR due to the
      many unfavourable NMR characteristics of (67)Zn. In this work, we have
      characterized the local structure around the Zn centres in several representative
      microporous zinc phosphites and zinc phosphates by acquiring natural abundance
      (67)Zn solid-state NMR spectra at ultrahigh magnetic field of 21.1 T. The
      observed line-shapes are mainly determined by the second order quadrupolar
      interaction. The NMR tensor parameters were extracted from the spectra and are
      related to the local geometry around the Zn centre. Computational study of the
      electric field gradient (EFG) tensor at Zn was performed using hybrid density
      functional theory (DFT) calculations at B3LYP level of theory on model clusters.
      The calculations using Projector Augmented-Wave (PAW) method were also carried
      out with the CASTEP code wherever it was possible. The work has shown that it is
      possible to study Zn environments in porous materials which often have very low
      Zn concentration by natural abundance (67)Zn SSNMR at very high magnetic fields.

PMID- 21850326
TI  - Pseudoceramines A-D, new antibacterial bromotyrosine alkaloids from the marine
      sponge Pseudoceratina sp.
AB  - Bioassay-guided fractionation of the CH(2)Cl(2)/MeOH extract of the Australian
      marine sponge Pseudoceratina sp. resulted in the purification of four new
      bromotyrosine alkaloids, pseudoceramines A-D (1-4), along with a known natural
      product, spermatinamine (5). The structures of 1-5 were determined by
      spectroscopic methods. Pseudoceramines A (1) and B (2) feature a rare
      bromotyrosyl-spermine-bromotyrosyl sequence, and pseudoceramine C (3) is the
      first example of bromotyrosine coupled with an N-methyl derivative of spermidine.
      Compounds 1-5 were screened for inhibition of toxin secretion by the type III
      secretion (T3S) pathway in Yersinia pseudotuberculosis. Compounds 2 and 5
      inhibited secretion of the Yersinia outer protein YopE (IC(50) = 19 and 6 MUM,
      respectively) and the enzyme activity of YopH (IC(50) = 33 and 6 MUM,
      respectively).

PMID- 21850327
TI  - Thermal reaction of [3,4]-benzo-8-substituted-3Z,5Z,7E-octatetraenes and quantum
      chemical study of the (8pi,6pi)-electrocyclisation.
AB  - The first example of thermal (8pi,6pi)-electrocyclisation of 1,3,5,7-octatetraene
      with one double bond embedded in an aromatic moiety is described. By this
      process, [3,4]-benzo-8-substituted octatetraene derivatives, the cis,trans-1-(o
      vinylphenyl)-4-(R = Me, Ph, 2-furyl)buta-1,3-dienes were transformed to a new
      endo-7-(R = Me, Ph, 2-furyl) and exo-7-(R = Me)-2,3-benzobicyclo[4.2.0]octa-2,4
      dienes. Mechanism of reaction was also studied by DFT quantum-chemical
      calculations. The M06/6-311+G(d,p)//M06/6-31+G(d,p) calculations indicate that
      formation of the single endo-isomer in the case of phenyl and 2-furyl
      substituents is determined by higher activation barriers for exo-6pi
      electrocyclisation than for 8pi-cycloreversion.

PMID- 21850328
TI  - Kinetics and mechanism of the oxidation of hydroxylamine by a {Mn3O4}4+ core in
      aqueous acidic media.
AB  - In this work we report the kinetics of oxidation of hydroxylamine by a trinuclear
      Mn(IV) oxidant, [Mn(3)(MU-O)(4)(phen)(4)(H(2)O)(2)](4+) (1, phen = 1,10
      phenanthroline), in aqueous solution over a pH range 2.0-4.0. The trinuclear
      Mn(IV) species (1) deprotonates in aqueous solution at physiological pH: 1 ? 2 +
      H(+); pK(1) = 4.00 (+/- 0.15) at 25.0  degrees C, I = 1.0 (M) NaNO(3). Both 1 and
      2 are reactive oxidants reacting with the conjugate acid of hydroxylamine, viz.
      NH(3)OH(+) where the deprotonated oxidant 2 reacts faster. This finding is in
      contrast to a common observation and belief that protonated oxidants react
      quicker than their deprotonated analogues. Mn(IV)(3) to Mn(II) transition in the
      present reaction proceeds through the intervention of a spectrally detected mixed
      valent Mn(III)Mn(IV) dimer that quickly collapses to Mn(II). The rate of the
      reaction was found to be lowered in D(2)O-enriched media in comparison to that in
      pure H(2)O media. An initial one electron one proton transfer to Mn(IV)(3)
      (electroprotic; 1e, 1H(+)) could be mechanistically conceived as the rate step.
      We also demonstrate by means of high level DFT studies that, among the two sets
      of Mn(IV) atoms in the trinuclear oxidant, the unique one that is coordinated
      with two phen ligands and two oxo-bridges is reduced to Mn(III) at the rate step.
      This is explained based on energetic and spin density calculations. Moreover,
      this result agrees with the charge distribution on the Mn atoms of the trinuclear
      complex.

PMID- 21850329
TI  - Nickel(II) complexes of tripodal 4N ligands as catalysts for alkane oxidation
      using m-CPBA as oxidant: ligand stereoelectronic effects on catalysis.
AB  - Several mononuclear Ni(II) complexes of the type [Ni(L)(CH(3)CN)(2)](BPh(4))(2) 1
      7, where L is a tetradentate tripodal 4N ligand such as N,N-dimethyl-N',N'
      bis(pyrid-2-ylmethyl)ethane-1,2-diamine (L1), N,N-diethyl-N',N'-bis(pyrid-2
      ylmethyl)ethane-1,2-diamine (L2), N,N-dimethyl-N'-(1-methyl-1H-imidazol-2
      ylmethyl)-N'-(pyrid-2-ylmethyl)ethane-1,2-diamine (L3), N,N-dimethyl-N',N'-bis(1
      methyl-1H-imidazol-2-ylmethyl)ethane-1,2-diamine (L4), N,N-dimethyl-N',N'
      bis(quinolin-2-ylmethyl)ethane-1,2-diamine (L5), tris(benzimidazol-2
      ylmethyl)amine (L6) and tris(pyrid-2-ylmethyl)amine (L7), have been isolated and
      characterized using CHN analysis, UV-Visible spectroscopy and mass spectrometry.
      The single-crystal X-ray structures of the complexes
      [Ni(L1)(CH(3)CN)(H(2)O)](ClO(4))(2) 1a, [Ni(L2)(CH(3)CN)(2)](BPh(4))(2) 2,
      [Ni(L3)(CH(3)CN)(2)](BPh(4))(2) 3 and [Ni(L4)(CH(3)CN)(2)](BPh(4))(2) 4 have been
      determined. All these complexes possess a distorted octahedral coordination
      geometry in which Ni(II) is coordinated to four nitrogen atoms of the
      tetradentate ligands and two CH(3)CN (2, 3, 4) or one H(2)O and one CH(3)CN (1a)
      are located in cis positions. The Ni-N(py) bond distances (2.054(2)-2.078(3) A)
      in 1a, 2 and 3 are shorter than the Ni-N(amine) bonds (2.127(2)-2.196(3) A)
      because of sp(2) and sp(3) hybridizations of the pyridyl and tertiary amine
      nitrogens respectively. In 3 the Ni-N(im) bond (2.040(5) A) is shorter than the
      Ni-N(py) bond (2.074(4) A) due to the stronger coordination of imidazole compared
      with the pyridine donor. In dichloromethane/acetonitrile solvent mixture, all the
      Ni(ii) complexes possess an octahedral coordination geometry, as revealed by the
      characteristic ligand field bands in the visible region. They efficiently
      catalyze the hydroxylation of alkanes when m-CPBA is used as oxidant with
      turnover number (TON) in the range of 340-620 and good alcohol selectivity for
      cyclohexane (A/K, 5-9). By replacing one of the pyridyl donors in TPA by a weakly
      coordinating -NMe(2) or -NEt(2) donor nitrogen atom the catalytic activity
      decreases slightly with no change in the selectivity. In contrast, upon replacing
      the pyridyl nitrogen donor by the strongly sigma-bonding imidazolyl or sterically
      demanding quinolyl/benzimidazolyl nitrogen donor, both the catalytic activity and
      selectivity decrease, possibly due to destabilization of the intermediate
      [(4N)(CH(3)CN)Ni-O](+) radical species. Adamantane is selectively (3 degrees /2
      degrees , 12-17) oxidized to 1-adamantanol, 2-adamantanol and 2-adamantanone
      while cumene is selectively oxidized to 2-phenyl-2-propanol. In contrast to
      cyclohexane oxidation, the incorporation of sterically hindering
      quinolyl/benzimidazolyl donors around Ni(ii) leads to a high 3 degrees /2 degrees
      bond selectivity for adamantane oxidation. A linear correlation between the
      metal-ligand covalency parameter (beta) and the turnover number has been
      observed.

PMID- 21850330
TI  - Reinvestigating 2,5-di(pyridin-2-yl)pyrazine ruthenium complexes: selective
      deuteration and Raman spectroscopy as tools to probe ground and excited-state
      electronic structure in homo- and heterobimetallic complexes.
AB  - The mono- (1) and dinuclear (2) ruthenium(II) bis(2,2'-bipyridine) complexes of
      2,5-di(pyridin-2-yl)pyrazine (2,5-dpp), for which the UV/Vis absorption and
      emission as well as electrochemical properties have been described earlier, are
      reinvestigated here by resonance, surface enhanced and transient resonance Raman
      spectroscopy together with selective deuteration to determine the location of the
      lowest lying excited metal to ligand charge transfer ((3)MLCT) states. The ground
      state absorption spectrum of both the mono- and dinuclear complexes are
      characterised by resonance Raman spectroscopy. The effect of deuteration on
      emission lifetimes together with the absence of characteristic bipy anion radical
      modes in the transient Raman spectra for both the mono- and dinuclear complexes
      bridged by the 2,5-dpp ligand confirms that the excited state is 2,5-dpp based;
      however DFT calculations and the effect of deuteration on emission lifetimes
      indicate that the bipy based MLCT states contribute to excited state
      deactivation. Resonance Raman and surface enhanced Raman spectroscopic (SERS)
      data for 1 and 2 are compared with that of the heterobimetallic complexes
      [Ru(bipy)(2)(2,5-dpp)PdCl(2)](2+)3 and [Ru(bipy)(2)(2,5-dpp)PtCl(2)](2+)4. The
      SERS data for 1 indicates that a heterobimetallic Ru-Au complex forms in situ
      upon addition of 1 to a gold colloid.

PMID- 21850332
TI  - A luminescent linear trinuclear Dy(III) complex exhibiting slow magnetic
      relaxation of single ion origin.
AB  - A luminescent trinuclear Dy(III) complex, in which the three Dy(III) centers with
      different geometries take a nearly linear disposition, shows the slow magnetic
      relaxation processes of single ion origin.

PMID- 21850331
TI  - Vectorized ferrocenes with estrogens and vitamin D2: synthesis, cytotoxic
      activity and docking studies.
AB  - Three ferrocene complexes vectorized with estrogens and vitamin D(2) were
      synthesized and fully characterized by spectroscopic, electrochemical and
      computational methods. The synthesis of these esters was accomplished by reacting
      ferrocenoyl chloride with the corresponding ROH groups (R = ergocalciferol,
      estradiol, estrone). The cytotoxicity of these complexes in HT-29 colon cancer
      and MCF-7 breast cancer cell lines was investigated in vitro. Only ferrocenoyl
      17beta-hydroxy-estra-1,3,5(10)-trien-3-olate showed good cytotoxic activity in
      both cell lines, exceeding those of ferrocenium and ferrocene. In MCF-7,
      ferrocenoyl 17beta-hydroxy-estra-1,3,5(10)-trien-3-olate exhibited remarkable
      IC(50), in the low micromolar range. This may be attributed to the presence of
      the estradiol vector. Docking studies between alpha-estrogen receptor ligand
      binding site and ferrocenoyl 17beta-hydroxy-estra-1,3,5(10)-trien-3-olate
      revealed some key hydrophobic interactions that might explain the cytotoxic
      activity of this ester.

PMID- 21850333
TI  - Dinuclear molybdenum cluster-catalyzed radical addition and polymerization
      reactions by tuning the redox potential of a quadruple bonded Mo2 core.
AB  - We developed dinuclear molybdenum cluster-catalyzed radical addition and
      polymerization reactions by tuning the redox potential of the Mo(2) core. A 2,4,6
      triisopropylbenzoate-supported Mo(2) complex acts as a catalyst for radical
      addition reactions of polyhaloalkanes to 1-alkenes and cyclopentene, while
      amidinate- and guanidinate-supported Mo(2) clusters are effective catalysts for
      the radical polymerization reaction of methyl methacrylate.

PMID- 21850334
TI  - Coordination chemistry and biological activity of 5'-OH modified quinoline-B12
      derivatives.
AB  - The consequences of structural modifications at the 5'-OH ribofuranotide moiety
      of quinoline modified B12 derivatives are discussed in regard of the coordination
      chemistry, the electrochemical properties and the biological behaviour of the
      compound.

PMID- 21850335
TI  - Outer membrane proteome and its regulation networks in response to glucose
      concentration changes in Escherichia coli.
AB  - Escherichia coli growth is a complicated process involved in many factors
      including the utilization of glucose. It has been reported that E. coli cell
      growth rate is closely related with glucose concentrations in the cell culture
      medium. However, the protein regulation networks in response to glucose
      concentration changes are largely unknown. In the present study, a sub-proteomic
      methodology has been utilized to characterize alterations of E. coli OM proteins
      in response to 0.02, 0.2 and 2% concentrations of glucose. In comparison with E.
      coli cells treated with 0.2% glucose concentration, downregulation of FhuE, FepA,
      CirA, TolC and OmpX and upregulation of LamB, FadL, OmpF, OmpT and Dps were
      detected in the E. coli cells treated with 0.02% glucose, and a decrease of TolC,
      LamB, OmpF, OmpT, OmpX, Dps and elevation of FhuE, FepA, CirA, YncD, FadL and
      MipA were found in 2% glucose. TolC, LamB and OmpT showed more important roles
      than other altered OM proteins. Furthermore, the interaction among these altered
      OM proteins was investigated, and protein interaction networks were
      characterized. In the networks, all proteins were interacted and regulated by
      others. TolC, LamB and Dps were the top three proteins that regulated more
      proteins than others, whereas CirA and OmpT were the top two proteins that were
      regulated by others. The protein networks could be modified correspondingly with
      the changes of glucose concentrations. The modifications included the addition of
      new OM proteins or the change of regulation direction. These findings suggest the
      important roles of the bacterial OM protein network in E. coli's responses to
      glucose concentration changes and other environment stresses.

PMID- 21850336
TI  - Complex nanostructures synthesized from nanoparticle colloids under an external
      electric field.
AB  - We present a novel method to synthesize complex nanostructured films through
      oriented connection of nanoparticles under an external electric field. Silver is
      taken as an example to validate the feasibility of this fabrication approach. The
      building blocks of the prepared silver films are able to be adjusted from
      nanoparticle to nanoflower, nanoplate, nanoslat, dendrite, and so forth, by
      either varying the deposition current density or changing the electrode. The
      obtained Ag complex structures show high SERS sensitivity. Importantly, this
      method can be extended to fabricate complex nanostructures of other materials,
      such as Cu(2)O. Further study of this new fabrication method may supply a simple
      and green method to realize various complicated nanostructures of different
      materials. The mechanism investigation is also important in understanding the
      assembly behavior of nanoparticles in the colloid under an external electric
      filed.

PMID- 21850337
TI  - Effect of butterfly-shaped sulfur-bridged ligand and counter anions on the
      catalytic activity and diastereoselectivity of organobismuth complexes.
AB  - In the direct Mannich reaction and synthesis of alpha,beta-unsaturated ketones,
      the use of organobismuth complexes as catalysts leads to high
      diastereoselectivity and products of single trans conformation. In this paper, we
      illustrate the relationship between structure and catalytic activity as well as
      diastereoselectivity of organobismuth complexes having a 5,6,7,12
      tetrahydrodibenz [c,f][1,5]thiobismocine framework as well as bearing a butterfly
      shaped sulfur-bridged ligand and tunable anions. With the exposed bismuth center
      acting as a Lewis acid site and the uncoordinated lone pair electrons of sulfur
      as a Lewis base site, the cationic organobismuth complexes work as bifunctional
      Lewis acid/base catalysts. Due to the steric influence of the butterfly-shaped
      structure and synergistic effect of Lewis acid and Lewis base centers, the
      complexes can direct substrate attack in organic synthesis. By adjusting the
      electron-withdrawing ability of the counter anions, the S-Bi bond strength can be
      regulated, leading to a significant change in Lewis acidity and Lewis basicity as
      well as catalytic activity. Through synergistic modulation of the above effects,
      one can control the diastereoselectivity of the organobismuth complexes for the
      generation of a single diastereoisomer.

PMID- 21850338
TI  - Theoretical study on the rearrangement of metallabenzenes to cyclopentadienyl
      complexes.
AB  - The thermodynamic and kinetic aspects of the rearrangement reactions of a series
      of metallabenzenes to cyclopentadienyl complexes have been investigated by DFT
      computational study in order to reveal how substituents on the metallacycle,
      ligands around the metal center, and metals affect the transformation. We found
      that substitutents and their locations on the metallacycle have a significant
      effect on the thermodynamics and kinetics of the rearrangement reactions.

PMID- 21850339
TI  - Coordination to metal centers: a tool to fix high energy conformations in organic
      molecules. Application to 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene and
      related macrocycles.
AB  - The solid state conformational preferences of ligand 2,4,4-trimethyl-1,5,9
      triazacyclododec-1-ene (L1) and its 9-methyl derivative (L2) in transition metal
      complexes have been determined by a probabilistic method using data retrieved
      from the Cambridge Structural Database. These macrocyclic compounds, as ligands,
      tend to adopt a preferential conformation (85% of cases). The ring containing the
      C=N bond adopts a distorted half-chair conformation, the ring defined by both the
      N-sp(3) shows a distorted envelope conformation, and the remaining ring exhibits
      a chair conformation. This conformation corresponds to the enantiomer pair
      R(N5)S(N9)S(P)/S(N5)R(N9)R(P). Molecular mechanics calculations demonstrate that
      this is a high energy conformation for the organic molecule, far from the energy
      minimum. Two other enantiomer pairs are observed in experimental structures. The
      influence of the coordination on the conformation of the organic ligands has been
      studied by DFT calculations, and a clear correlation with the geometry of the
      coordination sphere has been found.

PMID- 21850340
TI  - A flexible and unified strategy for syntheses of cladospolides A, B, C, and iso
      cladospolide B.
AB  - A simple, efficient and flexible strategy for the syntheses of cladospolides A-C
      and iso-cladospolide B is reported here. This strategy involves Julia-Kocienski
      olefination and Yamaguchi macrolactonization as key steps, starting from either d
      ribose or suitable tartaric acid esters. Although our initial efforts towards
      cladospolide A involving a ring closing metathetic approach were not successful,
      changing the mode of ring closure and the use of Julia-Kocienski olefination for
      the construction of the key intermediate solved this issue and paved the way for
      the completion of total syntheses of this class of natural products.

PMID- 21850341
TI  - Rhodium-catalyzed C-H activation and conjugate addition under mild conditions.
AB  - An efficient rhodium(III)-catalyzed C-H activation and subsequent conjugate
      addition was achieved under mild conditions. The reaction utilized inert arenes
      to replace stoichiometric organometallic reagents and can tolerate various
      functional groups as well as air and water.

PMID- 21850342
TI  - Novel synthesis of bifunctional catalysts with different microenvironments.
AB  - Acid-base bifunctional activity governed by -NH(2) group's microenvironment is
      evident from two different catalysts scrutinized by interchanging the location of
      -SO(3)H/NH(2) groups on periodic mesoporous ethylenesilica. The hydrophobic local
      environment plays a significant role in one-pot deacetalization/nitroaldol
      condensation.

PMID- 21850343
TI  - Nano-size amorphous calcium-manganese oxide as an efficient and biomimetic water
      oxidizing catalyst for artificial photosynthesis: back to manganese.
AB  - A nano-size amorphous calcium-manganese oxide shows efficient water oxidation
      activity in the presence of cerium(IV) ammonium nitrate.

PMID- 21850344
TI  - GPS-PUP: computational prediction of pupylation sites in prokaryotic proteins.
AB  - Recent experiments revealed the prokaryotic ubiquitin-like protein (PUP) to be a
      signal for the selective degradation of proteins in Mycobacterium tuberculosis
      (Mtb). By covalently conjugating the PUP, pupylation functions as a critical post
      translational modification (PTM) conserved in actinomycetes. Here, we designed a
      novel computational tool of GPS-PUP for the prediction of pupylation sites, which
      was shown to have a promising performance. From small-scale and large-scale
      studies we collected 238 potentially pupylated substrates for which the exact
      pupylation sites were still not determined. As an example application, we
      predicted ~85% of these proteins with at least one potential pupylation site.
      Furthermore, through functional analysis, we observed that pupylation can target
      various substrates so as to regulate a broad array of biological processes, such
      as the response to stress, sulfate and proton transport, and metabolism. The
      prediction and analysis results prove to be useful for further experimental
      investigation. The GPS-PUP 1.0 is freely available at: .

PMID- 21850345
TI  - Carbon-13 labelling strategy for studying the ATP metabolism in individual yeast
      cells by micro-arrays for mass spectrometry.
AB  - Isotopic labelling of cellular metabolites, used in conjunction with high-density
      micro-arrays for mass spectrometry enables observation of ATP metabolism in
      single yeast cells.

PMID- 21850346
TI  - Synthesis and characterization of self-assembled c-axis oriented Bi2Sr3Co2O(y)
      thin films by the sol-gel method.
AB  - Bi(2)Sr(3)Co(2)O(y) thin films are prepared on SrTiO(3) (100), (110) and (111)
      single crystal substrates using the sol-gel method. All the thin films are c-axis
      oriented regardless of the orientation of the substrate suggesting self-assembled
      c-axis orientation, and X-ray photoelectron spectroscopy results give evidence of
      coexistence of Co(3+) and Co(2+) ions in the derived films. Transmission
      electronic microscopy observations reveal that all samples are c-axis oriented
      with no obvious differences for different samples, and the c-axis lattice
      constant is determined as ~15 A suggesting the misfit structure. A
      phenomenological thermodynamic phase diagram for self-assembled c-axis
      orientation is established for misfit cobaltate-based films using chemical
      solution deposition. All samples behave like semiconductors due to the
      coexistence of Co(3+)/Co(2+) ions, and the resistivity at 350 K is ~47, 39 and 17
      mOmega cm for the thin films on SrTiO(3) (100), (110) and (111), respectively,
      whereas the Seebeck coefficient at 300 K is 97, 89 and 77 MUV K(-1). The
      successful attainment of Bi(2)Sr(3)Co(2)O(y) thin films with self-assembled c
      axis orientation will provide an effective prototype for investigation of growth
      mechanisms in complex oxide thin films with a misfit structure.

PMID- 21850347
TI  - Environmentally-safe bimetallic Ag@Co magnetic nanocomposites with antimicrobial
      activity.
AB  - In this communication we describe the synthesis, characterization and evaluation
      of the bactericide activity of a superparamagnetic bimetallic Ag/Co polymeric
      nanocomposite material for the treatment of bacteria contaminated aqueous
      solutions.

PMID- 21850348
TI  - Synthesis of biarylketones and phthalides from organoboronic acids and aldehydes
      catalyzed by cobalt complexes.
AB  - A cobalt-catalyzed addition of aryl- and alkenylboronic acids to aldehydes and
      phthalaldehyde to give the corresponding biarylketones and 3-aryl phthalides in
      good to excellent yields in one pot is described.

PMID- 21850349
TI  - Promoted dehydrogenation in ammine lithium borohydride supported by carbon
      nanotubes.
AB  - In this paper, ammine lithium borohydride (LiBH(4).NH(3)) was successfully
      impregnated into multi-walled carbon nanotubes (CNTs) through a melting
      technique. X-ray diffraction, scanning electron microscopy, Brunauer-Emmett
      Teller, and density measurements were employed to confirm the formation of the
      nanostructured LiBH(4).NH(3)/CNTs composites. As a consequence, it was found that
      the dehydrogenation of the loaded LiBH(4).NH(3) was remarkably enhanced, showing
      an onset dehydrogenation at temperatures below 100  degrees C, together with a
      prominent desorption of pure hydrogen at around 280  degrees C, with a capacity
      as high as 6.7 wt.%, while only a trace of H(2) liberation was present for the
      pristine LiBH(4).NH(3) in the same temperature range. Structural examination
      indicated that the significant modification of the thermal decomposition route of
      LiBH(4).NH(3) achieved in the present study is due to the CNT-assisted formation
      of B-N-based hydride composite, starting at a temperature below 100  degrees C.
      It is demonstrated that the formation of this B-N-based hydride covalently
      stabilized the [NH] groups that were weakly coordinated on Li cations in the
      pristine LiBH(4).NH(3)via strong B-N bonds, and furthermore, accounted for the
      substantial hydrogen desorption at higher temperatures.

PMID- 21850350
TI  - A transparent hybrid of nanocrystalline cellulose and amorphous calcium carbonate
      nanoparticles.
AB  - Nanocellulose hybrids are promising candidates for biodegradable multifunctional
      materials. Hybrids of nanocrystalline cellulose (NCC) and amorphous calcium
      carbonate (ACC) nanoparticles were obtained through a facile chemical approach
      over a wide range of compositions. Controlling the interactions between NCC and
      ACC results in hard, transparent structures with tunable composition, homogeneity
      and anisotropy.

PMID- 21850351
TI  - Preparation and characterisation of an equatorial para-adduct of (PhCH2)HC70 from
      the reaction of C70(2-) with benzyl bromide and H2O: addition effects in the
      polar and equatorial regions of C70.
AB  - Benzyl(hydro)[70]fullerene regioisomers with the addends in both the equatorial
      and polar regions of C(70) have been prepared via the reaction of dianionic C(70)
      with benzyl bromide and H(2)O. HRMS, UV-vis, (1)H, (13)C, HMQC (heteronuclear
      multiple quantum coherence) and HMBC (heteronuclear multiple bond coherence) NMR
      characterisations have shown that the addition in the equatorial region of C(70)
      affords a new (PhCH(2))HC(70) regioisomer with para-positioned addends across a
      six-membered ring, which is different from the "polar" regioisomers where the
      addends have an ortho-addition pattern. (1)H NMR characterisations have shown a
      much stronger shielding effect for the addends in the equatorial region with
      respect to the counterparts in the polar region of C(70), while cyclic
      voltammetry study has shown a surprising positive shift for the first reduction
      potential of the equatorial regioisomer with respect to those of the polar
      regioisomer and pristine C(70), suggesting that the equatorial region of C(70) is
      rather electropositive than electronegative. D(2)O experiment has shown a
      significant difference of the deuterated product distribution between the
      equatorial and polar regioisomers, which can be justified by the different
      acidity of the (PhCH(2))HC(70) regioisomers. Computational calculations have been
      carried out to rationalize the formation of the C(70)HR regioisomers.

PMID- 21850352
TI  - Light-driven conformational regulation of human telomeric G-quadruplex DNA in
      physiological conditions.
AB  - Human telomeric G-quadruplexes have raised broad interest not just due to their
      involvement in the regulation of gene expressions and telomerase activities but
      also because of their application in nanoarchitectures. Herein, three azobenzene
      derivatives 1-3 were synthesized with different substituent groups and their
      photo-isomerization properties were investigated by UV/Vis spectroscopy. Then
      circular dichroism spectroscopy (CD), fluorescence experiments and native-gel
      electrophoresis were performed to evaluate their capabilities of conformational
      photo-regulation both in the absence and presence of metal ions. The results
      suggested that the compounds synthesized can successfully regulate the
      conformation of human telomeric G-quadruplex DNA in K(+) conditions to some
      extent. This work will initiate the possibility for the design and intriguing
      application of light-induced switching to photoregulate the conformation of G
      quadruplex DNA under physiological conditions, providing a possible pathway to
      control G-quadruplex conformation in biological applications and also expanding
      the potential use of G-quadruplexes in nanomachines.

PMID- 21850353
TI  - Al(CN)6(3-) and Al(NC)6(3-) trianions.
AB  - At this time the smallest trianions observed in the gas phase are fluorinated
      fullerenes and large organic ring systems with attached sulfonic acid groups.
      Considerably smaller trianions have been predicted to be sufficiently stable for
      observation in mass spectrometers, but have not yet been detected. Here two
      isomers of the aluminium cyanide trianion, Al(CN)(6)(3-) and Al(NC)(6)(3-), are
      studied using ab initio methods. These two isomers are predicted to be
      electronically stable and to show substantial barriers with respect to
      dissociation of CN(-) units. Thus, the investigated trianions hit a sweat-spot
      regarding the possibility of detection, as they are by far more robust with
      respect to dissociation than alkali halide trianions, while at the same time
      materials from which these trianions can at least in principle be formed are much
      more readily available than those needed for producing small covalently bound
      trianions.

PMID- 21850354
TI  - The impact of ionic liquids on amyloid fibrilization of Abeta16-22: tuning the
      rate of fibrilization using a reverse Hofmeister strategy.
AB  - We have shown that the amyloid fibrilization of Abeta16-22 follows a reverse
      hofmeister trend in pILs. Fast fibrilization rates of seconds can be achieved.

PMID- 21850355
TI  - Playing with organic radicals as building blocks for functional molecular
      materials.
AB  - The literature has shown numerous contributions on the synthesis and
      physicochemical properties of persistent organic radicals but there are a lesser
      number of reports about their use as building blocks for obtaining molecular
      magnetic materials exhibiting an additional and useful physical property or
      function. These materials show promise for applications in spintronics as well as
      bistable memory devices and sensing materials. This critical review provides an
      up-to-date survey to this new generation of multifunctional magnetic materials.
      For this, a detailed revision of the most common families of persistent organic
      radicals-nitroxide, triphenylmethyl, verdazyl, phenalenyl, and dithiadiazolyl-so
      far reported will be presented, classified into three different sections:
      materials with magnetic, conducting and optical properties. An additional section
      reporting switchable materials based on these radicals is presented (257
      references).

PMID- 21850356
TI  - Hierarchical graphene nanocones over 3D platform of carbon fabrics: a route
      towards fully foldable graphene based electron source.
AB  - A three dimensional field emitter comprising hierarchical nanostructures of
      graphene over flexible fabric substrate is presented. The nanostructuring is
      realized through plasma treatment of graphene, coaxially deposited over
      individual carbon fiber by means of simple aqueous phase electrophoretic
      deposition technique. Hierarchical graphene nanocone, acting as a cold electron
      emitter, exhibits outstanding electron emission performance with a turn-on field
      as low as 0.41 V MUm(-1) and a threshold field down to 0.81 V MUm(-1). Electric
      field modification around the special woven like geometry of the underlying base
      fabric substrate serves as the booster to the nanostructured graphene related
      field amplification at the electron emission site. Superb robustness in the
      emission stability can be attributed to suppressed joule heating on behalf of
      higher inborn accessible surface area of graphene nanocone as well as excellent
      electrical and thermal conductivity of both the graphene and carbon fabrics.
      Superior flexibility of this high-performance graphene based emitter ensures
      their potential use in completely foldable and wearable field emission devices.

PMID- 21850358
TI  - A TiO2-nanotube-array-based photocatalytic fuel cell using refractory organic
      compounds as substrates for electricity generation.
AB  - A TiO(2)-nanotube-array-based photocatalytic fuel cell system was established for
      generation of electricity from various refractory organic compounds and
      simultaneous wastewater treatment. The present system can respond to visible
      light and produce obviously enhanced cell performance when a narrow band-gap
      semiconductor (i.e. Cu(2)O and CdS) was combined with TiO(2) nanotubes.

PMID- 21850357
TI  - Probing the local structure of dilute Cu dopants in fluorescent ZnS nanocrystals
      using EXAFS.
AB  - A local structure study of ZnS nanocrystals, doped with very low concentrations
      of Cu, was carried out using the EXAFS technique to better understand how Cu
      substitutes into the host lattice and forms Cu luminescence centers. We show that
      a large fraction of the Cu have three nearest neighbor S atoms and the Cu-S bond
      is significantly shortened compared to Zn-S, by ~0.08 A. In addition, the second
      neighbor Cu-Cu peak is extremely small. We propose that Cu occupies an interior
      site next to a S(2-) vacancy, with the Cu displaced towards the remaining S(2-)
      and away from the vacancy; such a displacement immediately explains the lack of a
      significant Cu-Cu peak in the data. There is no evidence for interstitial Cu
      sites (Cu(i)), indicating that no more than 2% of the Cu are Cu(i.) This study
      provides new insights into the local structure of the Cu dopant in ZnS without
      the presence of CuS nanoprecipitates that are present at higher Cu doping levels.

PMID- 21850359
TI  - Pb intercalation underneath a graphene layer on Ru(0001) and its effect on
      graphene oxidation.
AB  - Intercalation of Pb at graphene/Ru(0001) interfaces has been dynamically observed
      using in situ low energy electron microscopy and photoemission electron
      microscopy. A comparative study of Pb intercalation on the submonolayer and
      complete monolayer graphene surfaces suggest that the Pb intercalation happens
      through the open edges of graphene islands, starting at around 150  degrees C.
      Spatially-resolved low energy electron diffraction measurements reveal that the
      Pb-intercalated graphene overlayers are quasi-free-standing. The intercalated
      graphene sheets show lower reactivity to oxidation in O(2).

PMID- 21850360
TI  - Hydrogenation of arenes and N-heteroaromatic compounds over ruthenium
      nanoparticles on poly(4-vinylpyridine): a versatile catalyst operating by a
      substrate-dependent dual site mechanism.
AB  - A nanostructured catalyst composed of Ru nanoparticles immobilized on poly(4
      vinylpyridine) (PVPy) has been synthesized by NaBH(4) reduction of RuCl(3).3H(2)O
      in the presence of the polymer in methanol at room temperature. TEM measurements
      show well-dispersed Ru nanoparticles with an average diameter of 3.1 nm. Both
      powder XRD patterns and XPS data indicate that the Ru particles are predominantly
      in the zerovalent state. The new catalyst is efficient for the hydrogenation of a
      wide variety of aromatic hydrocarbons and N-heteroaromatic compounds
      representative of components of petroleum-derived fuels. The experimental data
      indicate the existence of two distinct active sites in the nanostructure that
      lead to two parallel hydrogenation pathways, one for simple aromatics involving
      conventional homolytic hydrogen splitting on Ru and a second one for N
      heteroaromatics taking place via a novel heterolytic hydrogen activation on the
      catalyst surface, assisted by the basic pyridine groups of the support.

PMID- 21850361
TI  - Selective oxidative debenzylation of mono- and oligosaccharides in the presence
      of azides.
AB  - When using benzyl ethers as permanent protecting groups in oligosaccharide
      synthesis selective oxidative debenzylation with NaBrO(3) + Na(2)S(2)O(4) under
      biphasic conditions is efficient and compatible with anomeric azides and many
      other functions.

PMID- 21850362
TI  - Mutual effects of disorder and order in fusion proteins between intrinsically
      disordered domains and fluorescent proteins.
AB  - Intrinsically disordered proteins are being paid an increasing amount of interest
      due to the understanding of the crucial role that flexible regions play in
      molecular recognition and in signaling. Accordingly, reports focusing on the
      structural and functional characterization of intrinsically disordered proteins
      or regions are growing exponentially. Relatively few studies have however been
      reported on the mutual effects of ordered and disordered moieties in artificial
      fusion proteins. In this review, we focus on the few available experimental data
      based on the use of chimeras in which fluorescent proteins were fused to
      disordered domains of different lengths, compactness and propensity to form
      secondary structures. The impact of the artificial fusion on the conformational
      and functional properties of the resulting proteins is discussed.

PMID- 21850363
TI  - Recurrent wheezing in infants: epidemiological changes.
AB  - OBJECTIVE: To determine epidemiological changes in recurrent wheezing among
      infants in Curitiba, Brazil. METHODS: This cross-sectional study used the
      questionnaire Estudio Internacional de Sibilancias en Lactantes (EISL). Parents
      of infants aged 12 to 15 months completed the instrument from August 2005 to
      December 2006 (phase I) and from September 2009 to September 2010 (phase III).
      RESULTS: Parents of 3,003 infants participated in phase I, and 22.6% of the
      infants had recurrent wheezing (>= 3 episodes). After 5 years, 1,003 parents
      completed the same questionnaire during phase III, and 19.8% of the infants had
      recurrent wheezing (p = 0.1). There was a reduction in symptom severity (p =
      0.001) and number of emergency department visits (p < 0.001), but not in number
      of hospitalizations (p = 0.12). Physician-diagnosed asthma was more frequent in
      phase III (p = 0.03). CONCLUSIONS: There were no changes in the prevalence of
      recurrent wheezing in infants, but there was an increase in physician-diagnosed
      asthma and a reduction in severity, which, however, did not affect the rate of
      hospitalizations.

PMID- 21850364
TI  - Sudden illness while driving a vehicle--a retrospective analysis of commercial
      drivers in Japan.
AB  - OBJECTIVE: We performed a retrospective analysis of commercial drivers to clarify
      the background of incidents of sudden illness while driving. METHODS: The
      analysis used reports submitted by employers to the Japan Ministry of Land,
      Infrastructure, Transport, and Tourism regarding commercial drivers who had been
      ordered to stop driving owing to health problems. RESULTS: Of 211 cases with an
      average work history of 15.2 years, there were 88 bus drivers, 70 taxi drivers,
      and 53 truck drivers, 36.0% of who had died as a result of their disease. Among
      taxi and truck drivers, more than 70% of incidents were due to cardiac, aortic,
      and cerebrovascular disease. More than 80% of these were unable to avoid traffic
      accidents caused by sudden illness. However, among bus drivers, cardiac, aortic,
      and cerebrovascular disease accounted for only 23.5% of incidents, and accidents
      were avoided in more than half of the cases. The duration between starting work
      and the incident time was significantly shorter among bus drivers [mean 3.3
      hours, standard deviation (SD) 3.1] than taxi (7.7 hours, SD 5.8) and truck (7.2
      hours, SD 6.3) drivers (P<0.01). CONCLUSIONS: The difference between the sudden
      illness rates of taxi and truck drivers and those of bus drivers is due to both
      reporting bias and differences in the awareness needed to prevent disabling
      events while driving. As a precaution, physicians should advise commercial
      drivers to stop driving as soon as they detect slight discomfort. To prevent
      accidents, more assertive health promotion aimed at professional drivers is
      needed.

PMID- 21850365
TI  - Sensitization and chronic beryllium disease at a primary manufacturing facility,
      part 1: historical exposure reconstruction.
AB  - OBJECTIVES: Previous epidemiologic studies of beryllium sensitization (BeS) and
      chronic beryllium disease (CBD) have reported inconsistent exposure-response
      relationships, likely due to exposure misclassification. The objective of this
      study was to develop historical estimates of size-selective personal exposure to
      beryllium for an epidemiologic study. METHODS: In 1999, a cross-sectional survey
      of workers hired after 1 January 1994 was conducted at a beryllium production
      facility. Personal exposure data from two air sampling surveys conducted in 1999
      were used to obtain total, respirable, and submicron particle baseline exposure
      estimates (BEE) for a job-exposure matrix (JEM). General area air samples
      collected from 1994-1999 were used to estimate annual changes in exposures
      (temporal factors) for 24 different process areas. Historical exposure estimates
      (HEE) were calculated by applying the temporal factors to the BEE. Workers were
      assigned HEE based on their work history, and their historical exposure profile
      was summarized as cumulative, average, or highest-ever job exposure. RESULTS:
      Changes in exposure over a 6-year period were observed in 10 of the 24 process
      areas with an overall mean decline of 18% per year. The overall total exposure
      for study participants over their work tenure ranged from: 0.001-34.44 MUg/m(3)
      year, 0.01-16.26 MUg/m(3), and 0.01-17.54 MUg /m(3) for cumulative, average, and
      highest-ever job, respectively. For respirable exposures, the ranges were: 0.001
      15.54 MUg/m(3)-year, 0.01-3.56 MUg/m(3), 0.01-5.54 MUg /m(3) for cumulative,
      average, and highest-ever job, respectively. CONCLUSIONS: Using this JEM,
      exposure-response relationships for BeS and CBD can be explored over a range of
      exposure metrics such as total, respirable, and submicron beryllium mass
      concentrations, including summary measures such as cumulative, average, or
      highest exposures, with the ultimate objective of elucidating a quantitative
      exposure-response relationship.

PMID- 21850366
TI  - The potential role of human osteoblasts for periprosthetic osteolysis following
      exposure to wear particles.
AB  - Aseptic loosening in total hip replacement is mainly caused by wear particles
      inducing inflammation and osteolysis. Wear can be a consequence of micromotions
      at the interface between implant and bone cement. Due to complex cellular
      interactions, different mediators (e.g. cytokines, proteinases) are released,
      which can promote osteolytic processes in the periprosthetic tissue followed by
      loosening of the implant. Furthermore, a reduced matrix synthesis and an induced
      apoptosis rate can be observed. The purpose of this study was to evaluate to what
      extent human primary osteoblasts exposed to wear particles are involved in the
      osteolysis. The viability, the secretion of collagen and collagenases and the
      variety of released cytokines after particle exposure was examined. Therefore,
      human osteoblasts were incubated with particles experimentally generated in the
      interface between hip stems with rough and smooth surface finishings as well as
      different material compositions (Ti-6Al-7Nb, Co-28Cr-6Mo and 316L) and bone
      cement mantle made of Palacos R containing zirconium oxide particles.
      Commercially pure titanium particles, titanium oxide, polymethylmethacrylate and
      particulate zirconium oxide were used as references. The results revealed
      distinct effects on the cytokine release of human osteoblasts towards particulate
      debris. Thereby, human osteoblasts released increased levels of interleukine (IL)
      6 and IL-8 after treatment with metallic wear particles. The expression of VEGF
      was slightly induced by all particle entities at lower concentrations. Apoptotic
      rates were enhanced for osteoblasts exposed to all the tested particles.
      Furthermore, the de novo synthesis of type 1 collagen was reduced and the
      expression of the matrix metalloproteinase (MMP)-1 was considerably increased.
      However, wear particles of Co-28Cr-6Mo stems seemed to be more aggressive,
      whereas particles derived from stainless steel stems caused less adverse cellular
      reaction. Among the reference particles, which caused less altered reactions in
      the metabolism of osteoblasts in general, ZrO2 can be assumed as the material
      with the smallest cell biological effects.

PMID- 21850367
TI  - Quinone methide tripterine, celastrol, induces apoptosis in human myeloma cells
      via NF-kappaB pathway.
AB  - Multiple myeloma is still an incurable hematological malignancy despite the
      development of high-dose chemotherapy with stem cell transplantation. However,
      the therapeutic approach for multiple myeloma has progressed significantly in the
      last decade. Novel agents such as bortezomib, thalidomide and lenalidomide have
      been introduced in clinics as expanded treatment options and have improved the
      outcomes of patients with multiple myeloma. More recently, the development of
      novel agents with better effects and lower side-effects for the treatment of
      multiple myeloma has became necessary in the clinical setting. Celastrol is a
      quinone methide triterpene derived from the medicinal plant Tripterygium
      wilfordii, which has been used to treat chronic inflammatory and autoimmune
      diseases. It also has been reported that celastrol has potential as an anticancer
      agent; however, the effects of celastrol against myeloma have never been
      reported. It has been reported that the mechanisms of action occur via the NF
      kappaB pathway. However, the effects of celastrol against multiple myeloma have
      never been reported. The recent clinical success of proteasome inhibitor
      bortezomib, which acts by inhibiting the NF-kappaB activity in patients with
      multiple myeloma led us to investigate the effects of celastrol on myeloma cells.
      Here we found for the first time that celastrol induces cell cycle arrest at the
      G1 phase followed by apoptosis in human myeloma cell line U266 cells. In
      addition, we showed that celastrol induces apoptosis of myeloma cells via
      activation of the caspase-3 and NF-kappaB pathways. These results suggest that
      celastrol would be an effective therapeutic agent in signal transduction therapy
      for the treatment of patients with multiple myeloma.

PMID- 21850368
TI  - Estrogen inhibits the effects of obesity and alcohol on mammary tumors and fatty
      liver.
AB  - The risk of developing breast cancer and fatty liver is increased by alcohol
      consumption. The objective of the present study was to determine if obesity and
      exogenous estrogen supplementation alter the effects of alcohol on mammary
      tumorigenesis and fatty liver. Ovariectomized female mice were (1) fed diets to
      induce overweight and obese phenotypes, (2) provided water or 20% alcohol, (3)
      implanted with placebo, low- or high-dose estrogen pellets and (4) injected with
      Met-1 mouse mammary cancer cells. Alcohol-consuming mice were more insulin
      sensitive and developed larger tumors than water consuming mice. Obese mice
      developed slightly larger tumors than control mice. Alcohol consumption and
      obesity increased growth factors, hepatic steatosis, activation of Akt, and
      inhibited the caspase-3 cascade. Estrogen treatment triggered the loss of body
      fat, induced insulin sensitivity, suppressed tumor growth, reduced growth factors
      and improved hepatic steatosis. Results show that the effects of alcohol on
      mammary tumor and fatty liver are modified by obesity and estrogen
      supplementation.

PMID- 21850369
TI  - Atorvastatin reduces functional deficits caused by photodynamic therapy in rats.
AB  - Clinical studies have indicated that photodynamic therapy (PDT) significantly
      prolonged the median survival of patients with gliomas. Experimental studies
      demonstrate that increasing optical energy and photosensitizer dose leads to
      increased volume of tumor necrosis. However, increasing the light dose delivered
      to the tumor may increase the risks of inducing permanent neurological deficits.
      In the current study, we sought to test the behavioral deficits induced in normal
      rats by brain PDT and the neurorestorative effects of atorvastatin on PDT-induced
      behavioral deficits. Considering its potential as a combination treatment of
      brain tumors, we investigated both in vitro and in vivo whether atorvastatin
      treatment promotes brain tumor growth. Non-tumored Fischer rats received PDT
      (n=18). Nine of the PDT-treated animals were treated with atorvastatin. Control
      animals underwent the same surgical procedure, but did not receive Photofrin and
      laser light. PDT-treated animals had significant behavioral deficits on days 2,
      5, 7, 9 and 14 after PDT, compared with surgery controls. PDT-treated animals
      receiving atorvastatin displayed significantly ameliorated behavioral deficits on
      days 7, 9 and 14 after PDT, compared to PDT-treated rats. In vitro tumor cell
      viability and growth were evaluated. Atorvastatin did not affect the growth of
      glioma cells. Fischer rats with intracranial 7-day-old 9L glioma tumor cell
      implantation were randomly subjected to no treatment, PDT alone, atorvastatin
      alone, or combined treatment with atorvastatin and PDT (6 rats/group). Our data
      indicate that atorvastatin did not promote tumor growth in either PDT treated and
      non-treated rats. However, atorvastatin significantly reduced the cell damage
      caused by PDT. To further test the mechanisms underlying the atorvastatin
      mediated reduction of functional deficits, we investigated the effects of
      atorvastatin on angiogenesis and synaptogenesis. Our data demonstrate that
      atorvastatin significantly induced angiogenesis and synaptogenesis in the PDT
      damaged brain tissue. Our data indicate that PDT induces functional deficits.
      Atorvastatin treatment promotes functional restoration after PDT, but does not
      promote glioma growth in vitro and in vivo. Atorvastatin reduces astrocyte and
      endothelial cell damage caused by PDT and induces angiogenesis and synaptogenesis
      after PDT. Thus consideration and further testing of the combination of
      atorvastatin and PDT for the treatment of glioma is warranted.

PMID- 21850370
TI  - Chondroitin sulfate expression predicts poor outcome in breast cancer.
AB  - Experimental studies have established that the sulfated glycosaminoglycans
      heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and
      growth factors that drive the malignant cell phenotype and the remodelling of the
      surrounding tumor stroma. However, the clinical relevance of these studies
      remains ill-defined. The present study investigates the significance of
      chondroitin sulfate expression in malignant cells and the stroma, respectively,
      of tumors from two independent cohorts of breast cancer patients (cohort I: 144
      patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples;
      ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox
      proportional hazards modelling were used to assess the relationship between
      chondroitin sulfate and recurrence-free and overall survival. High chondroitin
      sulfate expression in malignant cells was shown to predict shorter recurrence
      free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival
      (cohort I: P=0.044; cohort II: P<0.001) in both cohorts. In multivariate
      analysis, high chondroitin sulfate in malignant cells was shown to be an
      independent, predictive factor of poor overall survival (cohort I: hazard ratio
      2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71:
      95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the
      stroma showed no correlation with known markers of tumor aggressiveness or with
      clinical outcome in either cohort. Our data suggest that high chondroitin sulfate
      expression in malignant cells is associated with an adverse outcome in patients
      with primary breast cancer, supporting the idea of a functional and potentially
      targetable role of chondroitin sulfate in tumor disease.

PMID- 21850371
TI  - Pharmacological targeting of the constitutively activated MEK/MAPK-dependent
      signaling pathway in glioma cells inhibits cell proliferation and migration.
AB  - Activated mitogen-activated protein kinase MAPK cascade leading to ERK1/2
      phosphorylation is expressed in the majority of glial neoplasms and negatively
      correlates with survival time of patients. Here we show that ERK1/2 kinases are
      constitutively activated in glioma cell lines and stem cell-enriched primary
      cultures of glioblastoma. Pharmacological targeting of the activated MEK/ERK1/2
      module with the MEK inhibitor U0126 attenuates cell cycle progression (11 out of
      11 cell lines), impairs single (7 out of 10) and collective cell migration (9 out
      of 11) and abolishes single cell emigration from monolayers (4 out of 9).
      Attacking the activated MEK/ERK1/2 module thus partially blocks the tumorigenic
      potential of glial cancer cells on different levels and strongly suggests the
      application of combination molecularly targeted therapies to interfere more
      efficiently with glial tumor development and progression.

PMID- 21850372
TI  - Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular
      carcinoma at early and advanced stages in male Wistar rats.
AB  - Resveratrol, a phytochemical compound abundant in red wine and grapes, is known
      to affect cancer cells both in vitro and in vivo. A great amount of data have
      indicated the therapeutic benefits of resveratrol against cancer. However, it
      remains unclear whether these benefits are similar and equally effective in both
      the early and advanced stages of cancer or carcinogenesis. In this study, we
      report the effects of resveratrol in the early and advanced stages of
      hepatocarcinogenesis in a model of N-nitrosodiethylamine (DEN)-induced
      hepatocellular carcinoma (HCC) of male Wistar rats. For the experiment, rats were
      divided into different groups and treated with resveratrol either from day 1 of
      DEN administration for 15 days (pre-HCC), or after the development of HCC, i.e.,
      15-16 weeks after DEN administration (post-HCC), and compared to untreated HCC
      bearing rats. Biochemical analysis of alpha-fetoprotein, the known serum marker
      for HCC, and other serum and liver marker enzymes also demonstrated a decreased
      level upon resveratrol treatment compared to the untreated HCC-bearing rats. H&E
      staining of tissue sections from the liver showed alteration or transformation of
      liver parenchymatous tissue in DEN-induced HCC (at 15-16 weeks). Resveratrol
      treatment during early (on day 1 of DEN-induction) and advanced (weeks 17-18) HCC
      showed a marked difference in the tissue architecture compared to untreated HCC.
      Immunoblot analysis revealed that resveratrol intervention at both the early and
      advanced stages of DEN-induced HCC activated the apoptotic markers, such as PARP
      cleavage, caspase-3 activation, p53 up-regulation and cytochrome-c release. In
      addition, semiquantitative RT-PCR and immunoblot analysis demonstrated the up-
      and down-regulation of key apoptotic regulators, such as Bax and Bcl2,
      respectively, in a resveratrol treatment-dependent manner. Our results indicate
      that the administration of resveratrol either at the early or advanced stages of
      hepatocarcinogenesis is equally effective and involves the activation of the
      apoptotic pathway in male Wistar rats.

PMID- 21850373
TI  - Factors influencing RhoA protein distribution in the nucleus.
AB  - The aim of the present study was to observe the influence of various factors on
      the nuclear distribution of the RhoA protein in the SGC-7901 human gastric cancer
      cell line. Immunofluorescence microscopy was used to detect the localization of
      the RhoA protein, and Western blotting was used to determine the quantity of RhoA
      in the nucleus, cytosol and membrane. The results showed that H2O2-mediated
      damage and a lipopolysaccharide (LPS)-mediated inflammatory reaction caused the
      translocation of RhoA from the cytosol toward the nucleus. A P38 mitogen
      activated protein kinase (MAPK) inhibitor effectively hindered the LPS-triggered
      translocation of RhoA into the nucleus at the initial stage. Furthermore, the
      microtubule-targeted anticancer drug Taxol triggered the translocation of RhoA
      from the nucleus toward the cytosol and membrane, and Lysophosphatidic acid (LPA)
      enhanced this translocation. A protein modification inhibitor and a nucleus
      export inhibitor had no obvious effect on RhoA distribution in the nucleus. The
      results revealed that the distribution of RhoA protein in the nucleus was
      influenced by factors related to cell activities but was not affected by the
      modification of the protein. The translocation of RhoA into the nucleus was not
      dependent on the active nuclear import system.

PMID- 21850374
TI  - DNA demethylation is superior to histone acetylation for reactivating cancer
      associated genes in ovarian cancer cells.
AB  - To investigate the contributions of histone H3 lysine 9 acetylation and DNA
      methylation to p16, hMLH1 and MGMT silencing in ovarian cancer cells, we treated
      three ovarian cancer cell lines with Trichostatin A (TSA) and 5-aza-2'
      deoxycytidine and examined the status of mRNA expression, DNA methylation and
      histone H3 lysine 9 acetylation at the promoter of p16, hMLH1 and MGMT. The
      results showed that the hypermethylated silenced tumor-related genes in the
      ovarian cancer cells were characterized by hypoacetylated histone H3 lysine 9.
      Treatment with TSA resulted in the increase of histone H3 lysine 9 acetylation at
      the hypermethylated promoter, but with little effects on gene expression. TSA did
      not contribute to DNA demethylation. 5-aza-2'-deoxycytidine treatment caused DNA
      demethylation, increased histone H3 lysine 9 acetylation at the hypermethylated
      promoter and resulted in reactivation of p16, hMLH1 and MGMT. Combined treatments
      synergistically increased histone H3 lysine 9 acetylation accompanied by the re
      expression of the hypermethylated genes. To conclude, in ovarian cancer cells,
      DNA methylation and histone deacetylation act synergistically for the silencing
      of cancer-associated genes. DNA demethylation is superior to histone acetylation
      for reactivating cancer-associated genes.

PMID- 21850375
TI  - Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate
      cancer cells by up-regulation of death receptor 5.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type
      II transmembrane cytokine and a potent inducer of apoptosis in cancer cells.
      However, some cancer cells, particularly prostate cancer cells, such as LNCaP
      cells, were found to be resistant to TRAIL. In the present study, we demonstrate
      that the proteasome inhibitor ALLN significantly enhanced TRAIL-induced apoptosis
      by up-regulating TRAIL/Apo2L death receptor 5 expression in LNCaP cells. LNCaP
      cells were exposed to ALLN for 3 h and treated with recombinant TRAIL protein.
      ALLN alone induced a 20% cell death after a 3-h treatment; however, pretreatment
      with ALLN induced death to more than 80% of cells after 3 h of TRAIL treatment.
      ALLN also enhanced the cell death of TRAIL-sensitive/resistant prostate cancer
      and other cancer cell lines. Western blotting results showed that the combination
      of ALLN and TRAIL increased the levels of activated caspase-8, -3 and DR-5 in
      LNCaP cells. Furthermore, we observed an increase in DR-5 expression following 3
      h of treatment of ALLN alone. Taken together, our findings indicate that ALLN
      enhances TRAIL-induced apoptosis in LNCaP cells by up-regulating DR-5 expression.
      Thus, our results suggest that the combination of ALLN and TRAIL is a novel
      therapeutic strategy in TRAIL-resistant tumors.

PMID- 21850376
TI  - VEGF expression in mesenchymal stem cells promotes bone formation of tissue
      engineered bones.
AB  - The purpose of this study was to investigate the in vivo vascularization and bone
      formation activity of tissue-engineered bone constructed using bone marrow
      mesenchymal stem cells (MSCs) transfected with vascular endothelial growth factor
      (VEGF). The expression of VEGF165 in rat bone marrow MSCs was confirmed using RT
      PCR and immunohistochemistry. The MSCs were cultured together with nano
      hydroxyapatite/collagen (NHAC) to form tissue-engineered bone. Untransfected MSCs
      were used as controls. The mice were sacrificed, and the bone xenografts were
      analyzed using immunohistochemistry and quantified for the degree of
      vascularization and new bone formation. Based on our results, expression of the
      VEGF165 gene was detected using RT-PCR and immunohistochemistry following
      transfection and 4 weeks of selection. The co-cultured NHAC- and VEGF-transfected
      MSCs had significantly higher alkaline phosphatase (AP) activity compared to the
      controls (P<0.05). In the mice that received the tissue-engineered bone
      xenografts, clumps of cartilage cells, irregular bone-like tissue and
      microvessels were observed. The growth of these structures progressed with time.
      In the control mice, however, only small amounts of bone-like and fibrotic tissue
      were observed. The differences between the control and experimental groups were
      statistically significant (P<0.05). In conclusion, VEGF165-transfected bone
      marrow MSCs promotes vascularization of tissue-engineered bone and ectopic
      osteogenesis.

PMID- 21850378
TI  - The expression of human papillomavirus type 16 (HPV16 E7) induces cell cycle
      arrest and apoptosis in radiation and hypoxia resistant glioblastoma cells.
AB  - p53 is a widely known tumor-suppressor gene product that plays a key role in
      apoptotic cell death induced by DNA-damaging chemotherapeutic agents. Human
      glioma cells with functional p53 are known to be more resistant to gamma
      radiation. The aim of this study was to investigate whether the mutant
      glioblastoma cells (U87MG) transfected with human papilloma virus-type 16 E7
      (HPV16 E7) genes were capable of increasing sensitivity towards irradiation and
      hypoxia-induced cell death. The pLXSN retroviral vector expressed HPV-16E7 genes
      and was infected into the p53 mutated U87MG cell line. A specific amplification
      band of HPV16 E7 genes was detected in E7 genes and transfected in the U87MG cell
      line using a reverse transcriptase polymerase chain reaction. The experimental
      groups included the mutant glioblastoma cell line (U87MG), empty vector (pLXSN)
      transfected to mutant glioblastoma cell line (U87MG-LXSN), and retrovirus
      carrying HPV16 E7 genes transfected to the mutant glioblastoma cell line (U87MG
      E7). Hypoxic conditions were optimized using LDH assay and the subjects were
      exposed to hypoxia (16 and 20 h) and irradiation (9 h). Hoechst-propidium iodide
      (PI) staining results showed that hypoxia and irradiation increased the number of
      dead cells in the U87MG-E7 cells compared to U87MG and U87MG-LXSN cells. Results
      of the FACS analysis showed a similar pattern and recorded 80.44 and 58.94% of
      apoptotic cells in U87MG-E7 and U87MG cells, respectively. Cell cycle analysis by
      FACS revealed that, following irradiation and hypoxia, cells showed G2-M arrest.
      Additionally, the Western blot analysis results showed altered expression of E2F
      1, Rb and p53 in the irradiation- and hypoxia-induced U87MG-E7 cells compared to
      U87MG and U87MG LXSN cells. In conclusion, the over-expression of HPV16 E7 genes
      in U87MG cell lines increasd cell apoptosis and E2F1 expression compared to the
      HPV non-infected U87MG cells following irradiation and hypoxia. These results
      indicate that tumor-specific therapies that increase sensitivity towards
      radiation and hypoxic conditions may be beneficial for suppression of cancers.

PMID- 21850377
TI  - Induction of peroxisomal lipid metabolism in mice fed a high-fat diet.
AB  - Peroxisomes catalyze a range of essential metabolic functions, mainly related to
      lipid metabolism. However, their roles in obesity have yet to be clarified. The
      aim of this study was to investigate the correlation between obesity and
      peroxisomal lipid metabolism, particularly very long-chain fatty acid (VLCFA)
      metabolism, gene expression of peroxisomal beta-oxidation enzymes, peroxisomal
      ATP-binding cassette (ABC) transporter adrenoleukodystrophy (ABCD1) gene and its
      related gene, ABCD2, the elongation of the VLCFA (ELOVL) gene family and the
      transcriptional factors involved in the regulation of these genes, including
      peroxisome proliferator-activated receptor alpha (PPARalpha) and sterol
      regulatory element-binding protein. These factors were analyzed in livers from
      mice fed a high-fat diet (HFD) or a regular diet (RD) for 20 weeks. Furthermore,
      the amounts of plasma saturated and unsaturated fatty acids, including VLCFAs,
      were measured. A HFD induced hepatic gene expression of not only hydroxysteroid
      17-beta dehydrogenase 4 (HSD17b4) and sterol carrier protein 2 (SCP2) in
      peroxisomal beta-oxidation enzymes but also of ELOVL1, 2, 5 and 6, which are
      involved in the elongation of saturated and unsaturated VLCFAs. Furthermore,
      ABCD2 mRNA prominently increased in the HFD mice. The transcriptional regulator
      of these genes, PPARalpha, was also up-regulated in the HFD mice. VLCFA ratios
      including C24:0/C22:0, C25:0/C22:0 and C26:0/C22:0 are the most significant
      diagnostic markers of inherited peroxisomal diseases. These ratios were found to
      be low in the plasma of the HFD mice compared with the RD mice. The results
      suggest that HFD activates hepatic peroxisomal VLCFA metabolism, and may provide
      useful fundamental information to explain the role of peroxisomal function in
      obesity and lifestyle-related diseases.

PMID- 21850379
TI  - Sunitinib inhibits tumor vascularity and growth but does not affect Akt and ERK
      phosphorylation in xenograft tumors.
AB  - Sunitinib is a multikinase inhibitor approved for use in some human solid
      malignancies, including renal clear cell and gastrointestinal stromal cancer, and
      under investigation for many other neoplasias. In many preclinical cancer models
      sunitinib has shown anti-angiogenic and antitumor effects, acting mainly by
      inhibiting the activity of pro-angiogenic growth factor receptors. However, a
      percentage of tumors develop resistance to this treatment. The aim of this study
      was to identify novel potential molecular targets for the non- responsive tumors.
      The effects of sunitinib were investigated in xenograft tumors obtained by
      injecting HEK293 cells into NOD-SCID mice, focusing on the activity of growth
      regulating pathways involved in tumorigenesis. During 11 days of oral
      administration of sunitinib (40 mg/kg/day), the growth of tumors was monitored by
      measuring the mass volume by a caliper. At the end of the treatment, tumor
      specimens were histologically examined for microvessel density (MVD) and presence
      of necrosis, and the phosphorylation of ERK and Akt was analyzed in protein
      extracts by Western blotting. Moreover, the mRNA levels of VEGF and its receptor
      genes were measured by quantitative RT-PCR. Treatment with sunitinib elicited a
      clear reduction of the tumor growth, associated with a reduction of MVD,
      correlated with an increased number of necrotic cells. In contrast, the levels of
      phosphorylated Akt and ERK proteins were similar in treated and non-treated
      animals. The VEGF and VEGFR-1 and 2 transcripts were not affected by sunitinib
      treatment. In conclusion, these findings confirm the anti-angiogenic action as
      the major effect of sunitinib against tumor growth. In contrast, other important
      growth regulatory pathways involved in malignant trans-formation, such as the ERK
      MAPK and Akt/mTOR pathways are not affected by such a treatment, suggesting the
      use of specific inhibitors of these pathways as valid candidates for
      combinatorial therapies in sunitinib-resistant malignancies.

PMID- 21850380
TI  - Latent membrane protein 1 mediates the resistance of nasopharyngeal carcinoma
      cells to TRAIL-induced apoptosis by activation of the PI3K/Akt signaling pathway.
AB  - The 5-year survival rate of nasopharyngeal carcinoma (NPC) is still disappointing
      despite the much improved technologies in its treatment. Tumor necrosis factor
      related apoptosis inducing ligand (TRAIL) can selectively induce apoptosis in
      most tumor cells while sparing normal cells. However, its potential in the
      treatment of NPC has been limited by the eventual emergence of drug resistance.
      Latent membrane protein 1 (LMP1) is a major oncogene of the human DNA tumor virus
      Epstein-Barr virus (EBV) and is associated with the development of NPC and the
      emergence of chemo-resistance in NPC. In this study, we investigated the
      potential role of LMP1 in TRAIL resistance in CNE-1 NPC cells. Results show that
      overexpression of LMP1 could induce TRAIL resistance in NPC cells without
      influencing death receptors. The LMP1-induced TRAIL resistance is associated with
      increased expression of FLIP and elevated cleavage of caspase-8 without altering
      the TRAIL-mediated mitochondrial events and Bid cleavage. Knockdown of the FLIP
      gene with siRNA prevented the LMP1-induced TRAIL resistance. Furthermore, we
      found that overexpression of LMP1 activated Akt. Inhibition of Akt with LY294002
      completely prevented the LMP1-induced FLIP expression and TRAIL resistance.
      Together, these results show that LMP1 can inhibit the TRAIL-mediated apoptosis
      through activation of PI3K/Akt and expression of FLIP in CNE-1 NPC cells, and may
      provide new methods to prevent and reverse drug resistance in NPC.

PMID- 21850381
TI  - Genome-wide identification of possible methylation markers chemosensitive to
      targeted regimens in colorectal cancers.
AB  - PURPOSE: Few efficient methylation markers of chemosensitivity have been
      discovered. The genome-wide analysis of methylation markers is needed to identify
      chemosensitive candidates to targeted therapy. METHODS: This study describes a
      two-step process to select chemosensitive candidates of methylation genes. A
      genome-wide screening of methylation genes was performed using a Beadarray and an
      in vitro chemosensitivity assay of 119 colorectal cancers (CRCs). Ten candidate
      genes identified during the initial screening were verified by biological utility
      assessment using cell viability assays of transfected CRC cells. RESULTS: Five
      methylation genes related to sensitivity to bevacizumab regimens (RASSF1, MMP25,
      KCNQ1, ESR1, and GALR2) or cetuximab regimens (SCL18A2, GPX7, NID2, IGFBP3, and
      ALX4) were chosen during the first step. A viability assay revealed that GALR2
      overexpressing HCT116 cells were significantly more chemosensitive to bevacizumab
      regimens than control cells (P = 0.022 and 0.019 for bevacizumab with FOLFIRI and
      FOLFOX, respectively), concurrently verified on a caspase-3 activity assay. GPX7-
      or ALX4-overexpressed RKO cells were significantly less viable to cetuximab
      regimens compared to control cells (GPX7: P = 0.027 each for cetuximab with
      FOLFIRI and FOLFOX; ALX4: P = 0.049 and 0.003 for cetuximab with FOLFIRI and
      FOLFOX, respectively), but caspase-3 activity was not prominent in GPX7
      overexpressed RKO cells. CONCLUSIONS: Two novel genes, GALR2 and ALX4, have been
      identified as chemosensitive methylation candidates to bevacizumab and cetuximab
      regimens, respectively. As our study did not include a clinical association
      study, the two candidates should be validated in large clinical cohorts,
      hopefully predicting responsive patients to targeted regimens.

PMID- 21850382
TI  - Diagnosis value of focal liver lesions with SonoVue(r)-enhanced ultrasound
      compared with contrast-enhanced computed tomography and contrast-enhanced MRI: a
      meta-analysis.
AB  - PURPOSES: This study is aimed at evaluating diagnostic value of focal liver
      lesions (FLLs) with SonoVue((r))-enhanced ultrasound compared with contrast
      enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance
      imaging (CEMRI). METHODS: PubMed, EMBASE, and the Cochrane Central Register were
      searched for English language articles published from January 2000 to May 2011.
      Histopathologic analysis and/or close clinical and imaging follow-up (except CECT
      or CEMRI) for at least 6 months were used as golden reference. Sensitivity,
      specificity, summary receiver operating characteristic (SROC) curves, and area
      under the curve (AUC) were extracted to test heterogeneity. RESULTS: In 21
      included studies, for the SonoVue((r))-enhanced ultrasound studies, sensitivity
      was 88% (95% CI 87-90), specificity was 81% (95% CI 79-84), and 38.62 (95% CI
      13.64-109.35) for diagnostic odds ratio (DOR); for the CECT studies, sensitivity
      was 90% (95% CI 88-92), specificity was 77% (95% CI 71-82), and 30.84 (95% CI
      11.11-85.61) for DOR; for the CEMRI studies, sensitivity was 86% (95% CI 83-88),
      specificity was 81% (95% CI 76-85), and 27.63 (95% CI 11.28-67.70) for DOR.
      CONCLUSIONS: In comparison, SonoVue((r))-enhanced ultrasound had high pooled
      sensitivity and pooled specificity. SROC analysis showed the diagnostic value of
      FLLs with SonoVue((r))-enhanced ultrasound has no significant difference compared
      with CECT and CEMRI. SonoVue((r))-enhanced ultrasound is highly sensitive and
      specific in the characterization of FLLs to support an effective diagnostic
      method.

PMID- 21850383
TI  - Treatment strategies and prognostic factors of patients with primary germ cell
      tumors in the mediastinum.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical characteristics and
      survival outcomes of patients with primary mediastinal germ cell tumor (PMGCT) by
      identifying the prognostic factors and efficacies of different treatment
      modalities. METHODS: Fifty-five patients with PMGCT who were treated
      consecutively at Cancer Center, Sun Yat-sen University, Guangzhou, from 1988 to
      2010 were evaluated retrospectively. RESULTS: Fifty-two men and 3 women with a
      median age of 25 years were identified, of whom 17 (30.9%) had pure seminomatous,
      38 (69.1%) had nonseminomatous histology, 27 (49.1%) had tumor located at
      mediastinum, 20 (36.4%) had lung metastases and/or effusions, and 8 (14.5%) had
      distant metastases. Three treatments surgery, chemotherapy, and radiotherapy were
      performed in 11 (20%) patients, two treatments chemotherapy plus surgery or
      radiotherapy were performed in 25 (45.6%), and single treatment surgery or
      chemotherapy was performed in 17 (30.9%). The other two patients (3.6%) received
      no treatment. After a median follow-up time of 31.4 months, the 5-year survival
      rate was 52%. The median overall survival time was 87.9 months. Patients who
      received two treatments had the longest survival time of 118.3 months, P = 0.000.
      Those who had pure seminoma histology, whose tumor confined to the mediastinum
      and who achieved complete or partial remission at initial evaluation, who had
      complete resection and radiotherapy were considered to have better prognosis
      according to univariate analysis. On multivariate analysis, extension and
      response rate at initial evaluation were independently predictive of survival.
      CONCLUSIONS: Primary mediastinal germ cell tumor is rare with a dominant
      frequency in young male patients. Chemotherapy combined with local therapy like
      surgery or radiotherapy is a reasonable treatment strategy recommended. Extension
      and initial remission rate are independent prognostic factors.

PMID- 21850384
TI  - Microelectromechanical system-based diagnostic technology for cervical cancer.
AB  - PURPOSE: To determine the correlations of human papillomavirus (HPV) infection
      and alpha6 integrin up-regulation to the tumorigenesis and development of
      cervical cancer, and develop an on-chip antibody-based detection system using the
      microelectromechanical system (MEMS) device for recognizing and capturing
      cervical cancer cells from a mixed cell population. METHODS: We determined the
      efficiency of an antibody-based MEMS platform in recognizing and capturing
      cervical cancer cells. In addition, alpha6 integrin was used as a capture
      antibody bound to the channel surface. Channels 2 cm long * 50 cm wide with inlet
      and outlet diameters of 50 cm were formed in microfluidic polydimethylsiloxane
      (PDMS) chips. RESULTS: The overall chip measured 2 cm * 1.5 cm * 0.5 cm. Using a
      syringe micropump, 20,000 normal human cervical epithelial cells (HCEC), 20,000
      human cervical stromal cells (HCSC), and 20,000 human cervical cancer cells
      (HCCC) were suspended in PBS and flowed through the system at a rate of 20
      mL/min. At this flow rate, more than 45% of cancer cells were captured, whereas
      less than 5% of normal cells were captured. In addition, we confirmed the
      specificity of this system in cell-type targeting using PCR. CONCLUSIONS: MEMS is
      a sensitive and accurate method for capturing and enriching cells of interest.
      This technique is potentially useful in detecting cervical cancer at all stages,
      as well as other cancers with similar characteristics of cell surface antigen
      expression.

PMID- 21850386
TI  - Small bud of probable gastrointestinal stromal tumor within a laparoscopically
      resected gastric schwannoma.
AB  - Submucosal tumors (SMTs) of the gastrointestinal (GI) tract can be potentially
      difficulty to diagnose pathologically. We report a case of a gastric SMT that was
      resected by laparoscopic partial gastrectomy. Although the initial histological
      and immunohistochemical examinations considered the tumor as a schwannoma, mRNA
      based KIT genotyping indicated that the tumor included cells with KIT gene
      expression, and that a small number of cells carried a deletion mutation in exon
      11. Additional histopathological investigations revealed small aggregates of
      enlarged spindle to epithelioid cells, which were positive for KIT, CD34 and
      DOG1, and negative for S-100, scattered among the S-100-positive schwannoma
      cells. We consider that the cells carrying the KIT gene mutation are microscopic
      buds of a gastrointestinal stroma tumor (GIST), and to the best of our knowledge,
      this is the first report of probable GIST tissues identified in a schwannoma. Our
      observations raised the significance of genotyping for diagnosis of GI tract
      SMTs.

PMID- 21850385
TI  - Precise evaluation of chemotherapy-induced peripheral neuropathy using the visual
      analogue scale: a quantitative and comparative analysis of neuropathy occurring
      with paclitaxel-carboplatin and docetaxel-carboplatin therapy.
AB  - BACKGROUND: Some regimens of chemotherapy cause peripheral neuropathy such as
      pain in muscles and joints and numbness in the limbs. It is often difficult to
      estimate the neuropathy accurately and analyze it in detail. The aim of this
      study was to investigate whether chemotherapy-induced peripheral neuropathy could
      be appropriately estimated by using the visual analogue scale (VAS). METHODS:
      Ninety-three patients who received paclitaxel and carboplatin treatment (TC) or
      paclitaxel and docetaxel treatment (DC) participated in answering a questionnaire
      about peripheral neuropathy using the VAS. As a result, 134 cycles of TC and 79
      cycles of DC were evaluated. The average of VAS scores at every 10 days after
      each cycle of chemotherapy began was calculated. The daily change in VAS scores
      was also analyzed, and average VAS scores compared between TC and DC. RESULTS:
      Daily changes in peripheral neuropathy for each treatment could be demonstrated
      in detail. Pain and numbness had separate patterns of appearance. For both pain
      and numbness, a greater VAS score was observed in patients receiving TC than in
      those receiving DC. As the number of cycles grew, peripheral neuropathy became
      more serious in TC. CONCLUSIONS: The VAS could appropriately recognize the
      difference in peripheral neuropathy between TC and DC. Moreover, the VAS could
      also catch the change in peripheral neuropathy. This result suggests that the VAS
      system is a useful tool for managing peripheral neuropathy.

PMID- 21850387
TI  - Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1
      in selected patients with cirrhosis: a randomized controlled trial.
AB  - BACKGROUND: The renin-angiotensin system plays an important role in hepatic
      fibrosis and portal hypertension. We evaluated the long-term effects of
      olmesartan, an angiotensin type 1 (AT1) receptor blocker, on hemodynamics and
      liver fibrosis. METHODS: Forty-eight selected patients with cirrhosis were
      randomly divided into two groups of 24 patients each, those who received and
      those who did not receive olmesartan treatment for 1 year. Hepatic hemodynamic
      studies, and measurements of transforming growth factor-beta1 (TGF-beta1) and
      blood markers of hepatic fibrosis, including serum hyaluronic acid (HA), type IV
      collagen, and procollagen III N-terminal propeptide levels, were also performed
      at the beginning and end of the study. RESULTS: The median dose of the final drug
      administration was 20 mg (range 10-40 mg). Olmesartan reduced the hepatic venous
      pressure gradient (HVPG) by -12.9 +/- 9.1% (p = 0.035) after 1 year. No
      significant changes were seen in controls. Six of the 24 patients (25%) in the
      olmesartan group showed a >20% reduction of HVPG from baseline values. TGF-beta1
      was significantly decreased in patients who received olmesartan (7.0 +/- 8.2 vs.
      3.1 +/- 1.6 ng/mL, p = 0.046) but there was no decrease in the controls. A
      significant trend was shown by correlating HA and TGF-beta1 variations in
      cirrhosis patients (p = 0.018, r = 0.377). Fibrosis markers were unchanged at the
      end of the study in both groups. CONCLUSIONS: Olmesartan induced a mild reduction
      of portal pressure and TGF-beta1 for 1 year, but did not suppress hepatic
      fibrosis markers.

PMID- 21850388
TI  - Widespread cortical and subcortical brain atrophy in Parkinson's disease with
      excessive daytime sleepiness.
AB  - Our aim was to determine regional brain atrophy in Parkinson's disease (PD)
      patients with excessive daytime sleepiness (EDS) using voxel-based morphometry
      (VBM). From 71 consecutive probable PD patients, nine non-demented and non
      hallucinating patients with an Epworth Sleepiness Scale (ESS) >= 10 and 13 PD
      patients with an ESS <= 3 were selected as having EDS and as not having EDS,
      respectively. We also enrolled 22 healthy age- and sex-matched controls. Regional
      brain atrophy was assessed using VBM with 3-T magnetic resonance imaging. There
      was no difference in the dosage of dopaminergic drugs between PD patients with
      EDS and PD patients without EDS. PD patients with EDS showed marked atrophy in
      the gray matter of the frontal lobe, temporal lobe, occipital lobe, limbic lobe
      including the nucleus basalis of Meynert compared to controls (false discovery
      rate corrected p < 0.05). In contrast, PD patients without EDS did not show any
      significant difference in gray matter atrophy compared to controls (false
      discovery rate corrected p < 0.05). PD patients with EDS showed significant
      atrophy of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including
      the nucleus basalis of Meynert compared to PD patients without EDS (uncorrected p
      < 0.001). PD patients with EDS, even without dementia and hallucination, showed
      significant gray matter atrophy compared to PD patients without EDS and controls.

PMID- 21850389
TI  - Comparison of vertical and horizontal saccade measures and their relation to gray
      matter changes in premanifest and manifest Huntington disease.
AB  - Saccades are a potentially important biomarker of Huntington disease (HD)
      progression, as saccadic abnormalities can be detected both cross-sectionally and
      longitudinally. Although vertical saccadic impairment was reported decades ago,
      recent studies have focused on horizontal saccades. This study investigated
      antisaccade (AS) and memory guided saccade (MG) impairment in both the horizontal
      and vertical directions in individuals with the disease-causing CAG expansion
      (CAG+; n = 74), using those without the expansion (CAG-; n = 47) as controls.
      Percentage of errors, latency, and variability of latency were used to measure
      saccadic performance. We evaluated the benefits of measuring saccades in both
      directions by comparing effect sizes of horizontal and vertical measures, and by
      investigating the correlation of saccadic measures with underlying gray matter
      loss. Consistent with previous studies, AS and MG impairments were detected prior
      to the onset of manifest disease. Furthermore, the largest effect sizes were
      found for vertical saccades. A subset of participants (12 CAG-, 12 premanifest
      CAG+, 7 manifest HD) underwent magnetic resonance imaging, and an automated
      parcellation and segmentation procedure was used to extract thickness and volume
      measures in saccade-generating and inhibiting regions. These measures were then
      tested for associations with saccadic impairment. Latency of vertical AS was
      significantly associated with atrophy in the left superior frontal gyrus, left
      inferior parietal lobule, and bilateral caudate nuclei. This study suggests an
      important role for measuring vertical saccades. Vertical saccades may possess
      more statistical power than horizontal saccades, and the latency of vertical AS
      is associated with gray matter loss in both cortical and subcortical regions
      important in saccade function.

PMID- 21850390
TI  - Replacement of conventional doxorubicin by pegylated liposomal doxorubicin is a
      safe and effective alternative in the treatment of non-Hodgkin's lymphoma
      patients with cardiac risk factors.
AB  - Anthracyclines are a major component in the therapy of non-Hodgkin's lymphoma.
      However, due to their cardiac toxicity potential, curative and palliative
      treatment is often limited in patients with preexisting cardiac dysfunction.
      Liposomal doxorubicin formulations have been described to be less cardiotoxic
      than conventional doxorubicin. In the current study, we analyzed the efficacy and
      toxicity of pegylated liposomal doxorubicin (PLD) as constituent of the
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen
      replacing conventional doxorubicin in 21 patients with impaired cardiac left
      ventricular ejection fraction or preexisting cardiac risk factors and established
      diagnosis of diffuse large B cell lymphoma (n = 15), mantle cell lymphoma (n =
      3), follicular lymphoma (n = 1), and T cell lymphoma (n = 2). Overall and
      complete response rate were 85% and 40%, respectively. Event-free survival and
      overall survival after 2 years were 58%. One lethal event of acute cardiac death
      occurred during the first cycle in a patient with transposition of the big
      arteries, atrial flutter, and mitral valve regurgitation. In the remaining 20
      patients, no deterioration of myocardial function was observed in
      echocardiography performed before and after treatment. Seven cases of grade III
      IV hematological toxicity were observed as well as four episodes of neutropenic
      fever leading to hospitalization. No infection-related death occurred. However,
      25% of patients developed a hand-foot syndrome (HFS) leading to discontinuation
      of treatment. Importantly, the incidence of HFS increased considerably when PLD
      doses of 15 mg/m(2)/week were exceeded. We conclude that replacing conventional
      doxorubicin with PLD in polychemotherapy regimens such as CHOP is an efficient
      alternative in the treatment of patients with preexisting cardiac dysfunction.
      However, we recommend that PLD dose should not exceed 15 mg/m(2)/week. The
      rationale for the use of non-pegylated liposomal doxorubicin formulations should
      be evaluated in further studies.

PMID- 21850391
TI  - The ear in fetal MRI: what can we really see?
AB  - INTRODUCTION: The aim of this study was to investigate the ability to depict the
      components of the ear on brain-oriented fetal MRI studies. METHODS: Retrospective
      evaluation of the ear in MRI studies was performed post-mortem in 16 fetuses
      ranging from 15 to 22 gestation weeks (GW), and in 122 examinations in vivo of
      fetuses ranging from 20 to 38 GW. The cochlea, vestibular apparatus, middle ear,
      and external auditory canal were separately graded according to the components
      that were delineated. RESULTS: The components of the inner and middle ear were
      fully delineated in 100% of the post-mortem examinations, but the external
      auditory canals were only seen in only 25%. In the in vivo group, the imaging
      detail was much lower. Cochlear turns could be identified in 75% of the fetuses,
      the vestibule and the lateral semicircular canals in 72% andossicles in 70%.
      Before 25 GW, the ability to identify these individual parts was 50%, 30%, and
      33%, respectively, and above it was 89%, 93%, and 90% . In most cases, the
      external auditory canals could only be seen after 29 GW. CONCLUSION: In fetal MRI
      studies in vivo, it is possible to depict the components of the ear in the
      majority of the fetuses, in such a manner as to exclude major malformations.
      However, MRI might not provide enough detail to rule out pathology of the ear
      before 25 GW, this being a critical age for pregnancy management in many
      countries.

PMID- 21850392
TI  - Risk stratification and prevention of sudden death in patients with heart
      failure.
AB  - OPINION STATEMENT: For almost the past decade, recommendations for the use of
      implantable cardioverter defibrillators (ICDs) for primary prevention of sudden
      cardiac death have been based upon the left ventricular ejection fraction (LVEF).
      Current guidelines recommend an ICD for heart failure patients with LVEF <=35%
      and NYHA functional class of II or III; however, because the majority of heart
      failure patients who qualify for ICD implantation based on these criteria will
      never have an event requiring ICD therapy over several years of follow-up,
      additional methods of risk stratification for sudden death are clearly needed.
      Additionally, most of the nearly 300,000 cardiac arrests that occur each year
      occur in patients without heart failure or significant left ventricular
      dysfunction. To improve the identification of patients at risk for sudden death,
      several criteria other than ejection fraction have been proposed and studied.
      Markers of autonomic tone, including heart rate turbulence and QT dynamicity,
      have shown some ability to predict total mortality but not arrhythmic events.
      Microvolt T-wave alternans testing was initially thought to be highly predictive
      of life-threatening arrhythmias, but prospective large sub-studies of the MADIT
      II and SCD-HeFT trials have failed to show a predictive value for T-wave
      alternans testing. Newer markers for risk are based upon the detection of
      myocardial fibrosis, which forms the substrate for re-entrant and malignant
      ventricular tachyarrhythmias. Markers of collagen turnover or quantification of
      myocardial scar by MRI may hold the best promise for identifying patients at
      highest risk for sudden cardiac death and may also identify patients at high risk
      but with an ejection fraction above 35%, who are not currently recommended for
      ICD implantation.

PMID- 21850393
TI  - Predicting lymphatic drainage patterns and primary tumour location in patients
      with breast cancer.
AB  - Detailed knowledge of the lymphatic drainage of the breast is limited.
      Lymphoscintigraphy is a technique used during breast cancer treatment to
      accurately map patterns of lymphatic drainage from the primary tumour to the
      draining lymph nodes. This study aimed to create a statistical model to analyse
      the spread of breast cancer and primary tumour location using a large
      lymphoscintigraphy database, and visualise the results with a novel computational
      model. This study was based on lymphoscintigraphy data from 2,304 breast cancer
      patients treated at the Royal Prince Alfred Hospital Medical Centre in Sydney,
      Australia. Bayesian inferential techniques were implemented to estimate the
      probabilities of lymphatic drainage from each region of the breast to each
      draining node field, to multiple node fields, and to determine probabilities of
      tumour prevalence in each breast region. A finite element model of the torso and
      discrete model of the draining node fields were created to visualise these data
      and a software tool was developed to display the results (
      www.abi.auckland.ac.nz/breast-cancer ). Results confirmed that lymphatic drainage
      is most likely to occur to the axillary node field, and that there is significant
      likelihood of drainage to the internal mammary node field. The likelihood of
      lymphatic drainage from the whole breast to the axillary, internal mammary,
      infraclavicular, supraclavicular and interpectoral node fields were 98.2, 35.3,
      1.7, 3.1, and 0.7%, respectively; whilst the probability of lymphatic drainage to
      multiple node fields was estimated to be 36.4%. Additionally, primary tumours are
      most likely to develop in the upper regions of the breast. The models developed
      provide quantitative estimates of lymphatic drainage of the breast, giving
      important insights into understanding breast cancer metastasis and have the
      potential to benefit both clinicians and patients during breast cancer diagnosis
      and treatment.

PMID- 21850394
TI  - Prospective study of breast cancer risk for mutation negative women from BRCA1 or
      BRCA2 mutation positive families.
AB  - Published studies have reached contradictory conclusions regarding breast cancer
      risk for women from families segregating a BRCA1 or BRCA2 mutation who do not
      carry the family-specific mutation. Accurate estimation of breast cancer risk is
      crucial for appropriate counselling regarding risk management. The aim of this
      study is to prospectively assess whether breast cancer risk for mutation negative
      women from families segregating BRCA1 or BRCA2 mutations is greater than for
      women in the general population. Eligible women were 722 first-, second- and
      third-degree relatives of a BRCA1 or BRCA2 mutation carrier from 224 mutation
      positive (128 BRCA1, 96 BRCA2) families, had no personal cancer history at
      baseline, and had been tested and found not to carry the family-specific
      mutation. Self-reported family history of cancer, preventive interventions and
      verified cancer diagnoses were collected at baseline, and every 3 years
      thereafter. Median follow-up was 6.1 years (range 0.1-12.4 years). Time at risk
      of breast cancer was censored at cancer diagnosis or risk-reducing surgery.
      Standardised incidence ratios (SIR) were estimated by comparing observed to
      population incidences of invasive breast cancer using Australian Cancer Incidence
      and Mortality Books. Six cases of invasive breast cancer were observed. The
      estimated SIRs were 1.14 (95% CI: 0.51-2.53) overall (n = 722), 1.29 (95% CI:
      0.58-2.88) when restricted to first- and second-degree relatives of an affected
      mutation carrier (n = 442) and 0.48 (95% CI: 0.12-1.93) when restricted to those
      with no family history of breast cancer in the non-mutation carrying parental
      lineage (n = 424). There was no evidence that mutation negative women from
      families segregating BRCA1 or BRCA2 mutations are at increased risk of breast
      cancer. Despite this being the largest prospective cohort to assess this issue,
      moderately increased breast cancer risk (2-fold) cannot be ruled out.

PMID- 21850395
TI  - Iatrogenic displacement of tumor cells to the sentinel node after surgical
      excision in primary breast cancer.
AB  - Isolated tumor cells (ITC) are more common in the sentinel node (SN) after needle
      biopsy of a breast cancer, indicating iatrogenic displacement of tumor cells. We
      here investigate whether similar iatrogenic displacement occurs after surgical
      excision of a breast tumor. We compared the incidence of ITC in the SN of 414
      breast cancer patients with recent surgical excision to a group of 16,960
      patients without recent surgical procedure in a multivariate analysis by linking
      data from the Danish Breast Cancer Cooperative Group database and the Danish
      National Health Register. Moreover, the incidence of spread to non-SNs in
      patients with ITC in the SN after recent surgical excision was analyzed. We found
      an adjusted odds ratio on 3.73 (95% CI 2.57-5.43; P < 0.0001) for having ITC in
      the SN after surgical excision. The increase in ITC after surgical excision was
      especially seen in patients with ductal carcinomas (OR 4.66; 95% CI 3.03-7.19).
      None of the patients with ITC in SN after surgical excision had further spread to
      non-SNs compared to 12% in the group without recent surgical excision (P = 0.09).
      The nearly fourfold increase in ITC in the SN after surgical excision indicates
      that this procedure induces iatrogenic displacement of tumor cells. This
      displacement was more common in ductal carcinomas. We found no further
      dissemination to non-SNs in patients with ITC in the SN after recent surgical
      excision, and it is questioned whether these patients benefit from an axillary
      lymph node dissection.

PMID- 21850396
TI  - What can we learn from the age- and race/ethnicity- specific rates of
      inflammatory breast carcinoma?
AB  - Inflammatory Breast Carcinoma (IBC), the most aggressive type of breast tumor
      with unique clinicopathological presentation, is hypothesized to have distinct
      etiology with a socioeconomic status (SES) component. Using the Surveillance,
      Epidemiology and End Results (SEER) Program data for 2004-2007, we compare
      incidence rates of IBC to non-inflammatory locally advanced breast cancer (LABC)
      among racial/ethnic groups with different SES. The analysis includes women 20-84
      years of age. To examine evidence for the distinct etiology of IBC, we analyzed
      age-distribution patterns of IBC and non-inflammatory LABC, using a mathematical
      carcinogenesis model. Based on the Collaborative Staging Extension codes, 2,942
      incident IBC cases (codes 71 and 73) and 5,721 non-inflammatory LABC cases (codes
      40-62) were identified during the four-year study period. Age-adjusted rates of
      IBC among non-Hispanic White and Hispanic women were similar (2.5/100,000 in both
      groups). Similar rates were also found in non-inflammatory LABC in these two
      groups (4.8/100,000 and 4.2/100,000, respectively). In African-American women,
      the IBC (3.91/100,000) and non-inflammatory LABC (8.47/100,000) rates were
      greater compared with other ethnic/racial sub-groups. However, the ratio of rates
      of IBC/non-inflammatory LABC was similar among all the racial/ethnic groups,
      suggesting that African-American women are susceptible to aggressive breast
      tumors in general but not specifically to IBC. The mathematical model
      successfully predicted the observed age-specific rates of both examined breast
      tumors and revealed distinct patterns. IBC rates increased until age 65 and then
      slightly decreased, whereas non-inflammatory LABC rates steadily increased
      throughout the entire age interval. The number of critical transition
      carcinogenesis stages (m-stages) predicted by the model were 6.3 and 8.5 for IBC
      and non-inflammatory LABC, respectively, supporting different etiologies of these
      breast tumors.

PMID- 21850397
TI  - Enhancement of doxorubicin cytotoxicity of human cancer cells by tyrosine kinase
      inhibition of insulin receptor and type I IGF receptor.
AB  - The type I insulin-like growth factor receptor (IGF1R) contributes to cancer cell
      biology. Disruption of IGF1R signaling alone or in combination with cytotoxic
      agents has emerged as a new therapeutic strategy. Our laboratory has shown that
      sequential treatment with doxorubicin (DOX) and anti-IGF1R antibodies
      significantly enhanced the response to chemotherapy. In this study, we examined
      whether inhibition of the tyrosine kinase activity of this receptor family would
      also enhance chemotherapy response. Cis-3-[3-(4-methyl-piperazin-l-yl)
      cyclobutyl]-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine (PQIP)
      inhibited IGF1R and insulin receptor (InsR) kinase activity and downstream
      activation of ERK1/2 and Akt in MCF-7 and LCC6 cancer cells. PQIP inhibited both
      monolayer growth and anchorage-independent growth in a dose-dependent manner.
      PQIP did not induce apoptosis, but rather, PQIP treatment was associated with an
      increase in autophagy. We examined whether sequential or combination therapy of
      PQIP with DOX could enhance growth inhibition. PQIP treatment together with DOX
      or DOX followed by PQIP significantly inhibited anchorage-independent growth in
      MCF-7 and LCC6 cells compared to single agent alone. In contrast, pre-treatment
      with PQIP followed by DOX did not enhance the cytotoxicity of DOX in vitro.
      Furthermore, OSI-906, a PQIP derivative, inhibited IGF-I signaling in LCC6
      xenograft tumors in vivo. When given once a week, simultaneous administration of
      OSI-906 and DOX significantly enhanced the anti-tumor effect of DOX. In summary,
      these results suggest that timing and duration of the IGF1R/InsR tyrosine kinase
      inhibitors with chemotherapeutic agents should be evaluated in clinical trials.
      Long-term disruption of IGF1R/InsR may not be necessary when combined with
      cytotoxic chemotherapy.

PMID- 21850398
TI  - Global bioethics and communitarianism.
AB  - This paper explores the role of 'community' in the context of global bioethics.
      With the present globalization of bioethics, new and interesting references are
      made to this concept. Some are familiar, for example, community consent. This
      article argues that the principle of informed consent is too individual-oriented
      and that in other cultures, consent can be community-based. Other references to
      'community' are related to the novel principle of benefit sharing in the context
      of bioprospecting. The application of this principle necessarily requires the
      identification and construction of communities. On the global level there are
      also new uses of the concept of community as 'global community.' Three uses are
      distinguished: (1) a diachronic use, including past, present, and future
      generations, (2) a synchronic ecological use, including nonhuman species, and (3)
      a synchronic planetary use, including all human beings worldwide. Although there
      is a tension between the communitarian perspective and the idea of global
      community, this article argues that the third use can broaden communitarianism.
      The current development towards cosmopolitanism is creating a new global
      community that represents humanity as a whole, enabling identification of world
      citizens and evoking a sense of global solidarity and responsibility. The
      emergence of global bioethics today demonstrates this development.

PMID- 21850399
TI  - Histopathological changes in the gills and liver of Prochilodus lineatus from the
      Salado River basin (Santa Fe, Argentina).
AB  - This study evaluated the histopathological changes in gills and liver of
      Prochilodus lineatus inhabiting the Salado River basin. Fish were collected in
      four different sampling stations. The histological lesions in the tissues were
      examined under light microscopy and evaluated with quantitative analyses. The
      morphometric analysis of the gills showed a significant shortening of secondary
      lamellae and a lower percentage of area for gas exchange in fish from station 1
      (an urban area, located near the mouth of the Salado River) in comparison with
      fish gills from the reference site (station 4, a relatively pristine area).
      Moreover, a significantly higher area occupied with necrotic foci and the
      occurrence of an important inflammatory response were observed in fish liver of
      station 1 than the samples caught from other stations. Thus, histopathological
      evidences showed differences among sites, which could be related to different
      environmental conditions.

PMID- 21850401
TI  - Does the outcome of colonic flexure cancers differ from the other colonic sites?
AB  - BACKGROUND: Anecdotally, colonic flexure cancers (FC) appear to have a poorer
      prognosis compared to other colonic cancers (OCC). The aim of this study was to
      determine the outcome of colonic flexure cancers compared to the cancers of the
      rest of the colon. METHODS: Patients with a diagnosis of colonic cancer over a 5
      year period (2002-2006) were retrieved from a prospective database. Analysis was
      performed on flexure (hepatic/splenic) cancers versus remaining colon cancers.
      Overall, 1-, 3- and 5-year survival rates were calculated. All patients were
      followed up until death or end of study period (December 2008), with median
      follow-up of 32 months. Statistical analysis was performed using Kaplan-Meier
      with log rank statistic and Pearson chi-square test. RESULTS: Of 613 patients
      (54% males) with colonic cancers with median age 71 years, range (30-100), 67
      (10.9%) were FC (35 hepatic/32 splenic) and 546 (89.1%) were arising from OCC.
      The curative resection rates were FC 73.2% (41 of 56) and OCC 83.4% (359 of 435)
      (p = 0.05). Post-operative mortality for FC and OCC was 10.7% (6 of 56) and 4.2%
      (18 of 434), respectively (p = 0.04). FC presented at a more advanced Dukes stage
      (p = 0.003). Recurrence rates were 9.8% (4 of 41) for FC and 20.9% (75 of 359)
      for OCC sites (p = 0.088). The overall mean survival was 48.8 and 58.2 m for FC
      and OCC, respectively (p = 0.158). Of 1-, 3- and 5-year survival, only 1-year
      survival was significantly different between the two groups (OCC (85%) vs FC
      (75%), p = 0.018). CONCLUSIONS: Nearly one in ten colonic cancers is located at a
      flexure. Despite FC presenting at an advanced stage, leading to a lower curative
      resection rate, no significant survival difference was noted compared to other
      colonic sites, beyond the first year.

PMID- 21850400
TI  - Molecular cloning of Foxl2 gene and the effects of endocrine-disrupting chemicals
      on its mRNA level in rare minnow, Gobiocypris rarus.
AB  - Endocrine-disrupting chemicals (EDCs) can affect normal sexual differentiation in
      fish. Foxl2, one forkhead transcription factor, plays an important role in
      ovarian differentiation in the early development of the female gonad in mammals
      and fish. How EDCs affect Foxl2 expression is little known. In this study, we
      isolated a Foxl2 cDNA from the ovary of rare minnow Gobiocypris rarus and
      examined its expression during early development stages and in different adult
      tissues. Then, we analyzed Foxl2 expression in G. rarus juvenile following 3-day
      exposure to 17alpha- ethinylestradiol (EE2), 4-n-nonylphenol (NP), and bisphenol
      A (BPA). Alignment of known Foxl2 sequences among vertebrates showed high
      identity in forkhead domain and C-terminal region with other vertebrate proteins.
      Quantitative RT-PCR analysis showed that Foxl2 expression was linear decrease and
      cyp19a1a, the downstream target gene of Foxl2, had no correlation with Foxl2 from
      18 to 50 days post fertilization (dpf). Among different adult tissues, Foxl2 is
      mainly expressed in ovary, brain, gill, eye, and male spleen. In the 3-day
      exposure, the juvenile fish to EDCs, 0.1 nM EE2, and 1 nM BPA significantly up
      regulated the expression of Foxl2 gene, while NP had no effect on Foxl2
      expression. Altogether, these results provide basic data for further study on how
      Foxl2 mediates EDCs impact on the sexual differentiation in G. rarus.

PMID- 21850402
TI  - Presbypropria: the effects of physiological ageing on proprioceptive control.
AB  - Several changes in the human sensory systems, like presbycusis or presbyopia, are
      well-known to occur with physiological ageing. A similar change is likely to
      occur in proprioception, too, but there are strong and unexplained discrepancies
      in the literature. It was proposed that assessment of the attentional cost of
      proprioceptive control could provide information able to unify these previous
      studies. To this aim, 15 young adults and 15 older adults performed a position
      matching task in single and dual-task paradigms with different difficulty levels
      of the secondary task (congruent and incongruent Stroop-type tasks) to assess
      presumed age-related deficits in proprioceptive control. Results showed that
      proprioceptive control was as accurate and as consistent in older as in young
      adults for a single proprioceptive task. However, performing a secondary
      cognitive task and increasing the difficulty of this secondary task evidenced
      both a decreased matching performance and/or an increased attentional cost of
      proprioceptive control in older adults as compared to young ones. These results
      advocated for an impaired proprioception in physiological ageing.

PMID- 21850405
TI  - Therapeutics for childhood neurofibromatosis type 1 and type 2.
AB  - OPINION STATEMENT: Neurofibromatosis type 1 (NF1) and type 2 (NF2) are
      genetically and medically distinct neurocutaneous disorders that are both
      associated with tumors affecting the central and peripheral nervous systems. NF1
      has a frequency of 1 in 3,000, compared with 1 in 30,000 for NF2. Careful
      surveillance is important for both conditions, to allow early identification and
      treatment of complications. The most common and important problems in NF1 are
      cognitive impairment, optic pathway gliomas, plexiform neurofibromas, and
      orthopaedic issues. Early intervention and tailored educational programs are
      indicated for learning difficulties. Attention deficit hyperactivity disorder may
      be amenable to treatment with stimulant medication. A clinical trial is under way
      to evaluate lovastatin in the treatment of cognitive problems in children with
      NF1. Chemotherapy with vincristine and carboplatin is the current standard of
      care for symptomatic optic pathway gliomas, but new agents with improved efficacy
      are needed. Plexiform neurofibromas may be treated with surgery, but often recur.
      To date, no medical therapy has proven effective in limiting plexiform
      neurofibroma growth, but several candidate medications are under consideration in
      clinical trials. Malignant peripheral nerve sheath tumors may arise in
      preexisting plexiform neurofibromas, so changes in tumor growth or an increase in
      pain or focal neurologic deficit should prompt further investigation and early
      treatment with wide surgical resection, with or without adjuvant chemotherapy or
      radiotherapy. Specialist surgical intervention may be needed for scoliosis and
      tibial pseudoarthrosis. In NF2, surgical treatment remains a cornerstone of
      management for symptomatic progressive vestibular schwannomas, meningiomas, and
      spinal tumors. Vascular endothelial growth factor inhibitors show promise for the
      treatment of vestibular schwannomas, with the aim of delaying surgery, and other
      targeted molecular therapies are becoming available as investigational options.
      Hearing aids and brainstem and cochlear implants have a role in optimizing
      functional hearing in some patients. Specialist ophthalmology input should be
      arranged to monitor for ophthalmologic complications. A coordinated effort is
      needed to enroll NF1 and NF2 patients in international multicenter clinical
      trials of promising new pharmacologic agents. Genetic testing is useful for
      prenatal diagnosis and may be important in understanding individual responses to
      novel medical therapies in the future. Effective transition to adult services is
      important, considering the likelihood of further complications in the adult
      years.

PMID- 21850403
TI  - Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1
      neuropathogenesis.
AB  - Anti-retroviral therapy (ART) has had a tremendous impact on the clinical
      outcomes of HIV-1 infected individuals. While ART has produced many tangible
      benefits, chronic, long-term consequences of HIV infection have grown in
      importance. HIV-1-associated neurocognitive disorder (HAND) represents a
      collection of neurological syndromes that have a wide range of functional
      cognitive impairments. HAND remains a serious threat to AIDS patients, and there
      currently remains no specific therapy for the neurological manifestations of HIV
      1. Based upon work in other models of neuroinflammation, kappa opioid receptors
      (KOR) and synthetic cannabinoids have emerged as having neuroprotective
      properties and the ability to dampen pro-inflammatory responses of glial cells;
      properties that may have a positive influence in HIV-1 neuropathogenesis. The
      ability of KOR ligands to inhibit HIV-1 production in human microglial cells and
      CD4 T lymphocytes, demonstrate neuroprotection, and dampen chemokine production
      in astrocytes provides encouraging data to suggest that KOR ligands may emerge as
      potential therapeutic agents in HIV neuropathogenesis. Based upon findings that
      synthetic cannabinoids inhibit HIV-1 expression in human microglia and suppress
      production of inflammatory mediators such as nitric oxide (NO) in human
      astrocytes, as well as a substantial literature demonstrating neuroprotective
      properties of cannabinoids in other systems, synthetic cannabinoids have also
      emerged as potential therapeutic agents in HIV neuropathogenesis. This review
      focuses on these two classes of compounds and describes the immunomodulatory and
      neuroprotective properties attributed to each in the context of HIV
      neuropathogenesis.

PMID- 21850406
TI  - CD30+ neoplasms of the skin.
AB  - Cutaneous T-cell lymphomas (CTCLs) are subdivided by lesion morphology, behavior,
      and surface receptors. Mycosis fungoides (MF) and Sezary syndrome (SS) are
      derived from CD4+ effector or central memory T-cells respectively. MF presents
      clinically as patches, plaques, or tumors, and SS presents with erythroderma.
      After MF/SS, the next most common CTCLs are CD30+ lymphoproliferative disorders:
      self-regressing lymphomatoid papulosis (LyP) or tumors of anaplastic large-cell
      lymphoma (ALCL), which express high levels of tumor necrosis factor death
      receptor member 8, also called CD30. Although MF is not considered to be a CD30+
      lymphoproliferative disorder, MF may co-exist with LyP lesions, and MF may
      express CD30, especially in the setting of large-cell transformation. The
      development of targeted therapy for CD30+ CTCLs will help in understanding the
      importance of the CD30 death receptor in pathogenesis and will improve treatment
      options.

PMID- 21850407
TI  - Expression of cell growth negative regulators MEG3 and GADD45gamma is lost in
      most sporadic human pituitary adenomas.
AB  - We aimed at the evaluation of MEG3 and GADD45gamma expression in sporadic
      functioning and clinically non-functioning human pituitary adenomas,
      morphologically characterized by immunohistochemistry analysis and their
      association with clinical features. Thirty eight patients who had undergone
      hypophysectomy at Sao Jose Hospital of Irmandade Santa Casa de Misericordia in
      Porto Alegre, Brazil, were included in this study. We evaluated tumor-type
      specific MEG3 and GADD45gamma expression by qRT-PCR in the pituitary adenomas,
      and its association with clinical features, as age, gender and tumor size,
      obtained from medical records. The patients consisted of 21 males and 17 females
      and the mean age was 47 +/- 14 (mean +/- SD), ranging from 18 to 73 years-old. Of
      these 14 were clinically non-functioning, 10 GH-secreting, 9 PRL-secreting, and 5
      ACTH-secreting pituitary adenomas. All samples were macroadenomas, except four
      ACTH-secreting tumors, which were microadenomas. In summary, MEG3 and GADD45gamma
      expression was significantly lost in most clinically non-functioning adenomas (78
      and 92%, respectively). Other assessed pituitary tumor phenotypes expressed both
      genes at significantly different levels, and, in some cases, with overexpression.
      There was no significant association between gene expression and the analyzed
      clinical features. Our results confirm the previous report, which indicated that
      MEG3 and GADD45gamma expression is lost in the majority of human pituitary
      tumors, mainly in clinically-nonfunctioning adenomas. Functioning tumors had
      differences of relative expression levels. The two groups of tumors are probably
      genetically different and may have a different natural history.

PMID- 21850408
TI  - Initial experience with a newly developed antirefluxive ureter stent.
AB  - The objective of this study was to assess the functional efficacy of newly
      developed antirefluxive ureter stents (DJ), by performing immediate post-stenting
      cystograms on patients with acute ureteral obstruction requiring a DJ stent, and
      assessing stent-related symptoms by means of ureteral stent symptoms
      questionnaire (USSQ). Patients with acute hydronephrosis requiring internal
      drainage were randomized to receive either an antirefluxive DJ or a conventional
      DJ (7 Fr., 26 cm, polyurethane, Urovision((r)), Germany). Mean stone size was
      6.64 +/- 3.33 and 6.5 +/- 3.54 mm. Immediately after correct placement of the DJ,
      200 ml of diluted contrast media was introduced into the bladder under
      fluoroscopic control to detect vesicoureteral reflux (VUR). Patients completed
      German versions of the USSQ on days 2 and 7 following stent placement, and 1 week
      after stent removal. The results were analyzed. 13 conventional and 16
      antirefluxive stents were placed in 29 patients. Reflux was documented in eight
      conventionally stented patients (62.5%). Two of the 16 patients with
      antirefluxive stents (22%) presented reflux. 1 week after stent implantation, the
      mean pain value was 1.1 in the antirefluxive group and 3 in the standard group (p
      < 0.062). Flank pain during micturition occurred after 2 days in seven patients
      (58%) with standard stents and in three patients (33%) with antirefluxive stents
      (p < 0.23). 1 week after stent insertion, flank pain had dropped to 40% in the
      standard group and 11% in the antirefluxive group (p < 0.3). Our initial
      experience showed that the antirefluxive system might be effective in terms of
      reflux prevention and reduction of stent related symptoms especially during
      sexual intercourse.

PMID- 21850409
TI  - Can the CT planning image determine whether a kidney stone is radiopaque on a
      plain KUB?
AB  - Almost all kidney stones are CT positive. Before a CT scan can be done a CT
      planning image (CTI) is generated in order to select the exact scanning area. The
      CTI looks approximately like a normal kidney-ureter-bladder abdominal radiography
      (KUB) but with reduced quality. It has been used as a guide, assuming that if the
      kidney stone could be seen on the CTI the kidney stone also would be visible on a
      conventional plain KUB (radiopaque). From the perspective of diagnosis and
      treatment as well as follow-up it is of importance to know whether a kidney stone
      is radiopaque or not. The aim of this study was to evaluate whether the CTI
      actually can predict radiopacity. CT scans and corresponding KUB's were analysed
      in 76 consecutive kidney stone patients. The CT scan and the KUB were performed
      on the same day. All patients were examined with the same CT scanner (64 slice GE
      light speed VCT). Three radiologists evaluated the images in plenum. The
      following was recorded regarding the kidney stones: X-ray positive (radiopaque on
      KUB), CTI positive (radiopaque on CTI), location (a kidney, b upper two-thirds of
      ureter and c lower one-thirds of ureter including the bladder), size and
      Hounsfield units (HU). We also measured the patient's 'anterior-posterior depth'
      (APD) at the kidney stone level in axial plane, and whether the stone was
      homogeneous/inhomogeneous. 54 of the 76 patients (71%) had radiopaque stones on
      KUB. 43 (57%) of these also could be seen on the CTI, resulting in a positive
      predicting value (PPV) of 100% and a negative predictive value (NPV) of 67%. In
      the 54 KUB positive kidney stones the mean kidney stone diameter was 7 mm (2-30
      mm), mean HU's 1,007 (294-1,782 HU), location: a:32, b:9 and c:13 patients. APD
      was mean 23.6 cm (13-39 cm). In the KUB positive and CTI negative kidney stones
      (11 patients) mean kidney stone diameter was 4 mm (2-9 mm), mean HU's 742 (294
      1,253 HU), location: a:32, b:9 and c:13 patients. APD in this group was mean 26.1
      cm (13-37 cm). If the kidney stone can be seen on the CTI it is also visible on a
      plain KUB (PPV 100%). The CTI do, however, underestimate the radiopacity of a
      stone on a plain KUB (NPV 67%). Kidney stone HU > 742, stone location in the
      kidney and proximal ureter and APD < 26 cm independently predict agreement
      between CTI and KUB with regard to radiopacity.

PMID- 21850410
TI  - Left ventricular systolic function deterioration during dobutamine stress
      echocardiography as an early manifestation of diabetic cardiomyopathy and
      reversal by optimized therapeutic approach.
AB  - Diabetes mellitus has been associated with changes in the structure and function
      of the myocardium manifesting in the early stages of the disease as subtle
      systolic and diastolic dysfunction; the role of dobutamine stress
      echocardiography (DSE) in this setting remains unclear. We sought to evaluate the
      prevalence of dobutamine-induced systolic dysfunction amongst diabetic patients
      with normal at rest left ventricular ejection fraction and no coronary artery
      disease and to investigate whether an optimized therapeutic approach can reverse
      these abnormalities. 1,363 patients with DM referred to our echocardiography
      laboratory for DSE between January 2008 and June 2010 were prospectively
      investigated. Patients with normal left ventricular ejection fraction (LVEF) at
      rest and significant deterioration during peak dobutamine infusion (defined as a
      >=10% decrease) in the absence of coronary artery disease or vasospasm were
      enrolled. They received on top of their usual treatment 5 mg perindopril and had
      their glycemic control intensified. At 60 days, all of them were controlled for
      clinical status and underwent a control DSE. 18 patients were included, there
      were 9 males and 9 females, mean age was 66.1 +/- 10.2 years. All the patients
      had type II DM with a mean duration of 12.7 +/- 6.6 years. They all had normal at
      rest echocardiographic findings with no wall motion abnormalities; mean LVEF was
      62 +/- 6%. At peak dobutamine, LVEF significantly deteriorated in all the
      patients with a mean 15 +/- 5% decrease compared to baseline. After therapeutic
      optimization, Glycated haemoglobin improved from 8.53 +/- 2.05% to 6.8 +/- 0.6%
      (delta HbA1C = 1.73%, P = 0.001), mean LVEF at peak dobutamine infusion evolved
      from 47.17 +/- 4.2% pre-optimization to 58 +/- 4.8% at control (10.83%
      improvement; P < 0.001). In patients with DM and normal at rest LVEF, Dobutamine
      infusion during DSE can induce a significant deterioration in LVEF in the absence
      of coronary artery disease or vasospasm. This specific condition could be largely
      reversed through an optimized therapy based on a tighter metabolic control and a
      more stringent renin-angiotensin-aldosterone system inhibition.

PMID- 21850411
TI  - Radioprotection (un)awareness in cardiologists, and how to improve it.
AB  - In 2010 the International Atomic Energy Agency launched the "3 A's campaign":
      Audit, Appropriateness and Awareness for radiological justification, which is an
      effective tool for cancer prevention. Cardiologists prescribe the majority of
      radiological testing, but their awareness of doses and risks of ionizing cardiac
      imaging test is low. To assess radioprotection awareness of prescribing and
      practicing physicians (mainly cardiologists) before and after a radioprotection
      course. We held a 1-day 6-h primer of radioprotection for a limited number (20
      35) of physicians. The course offered 8 continuing education credits from the
      Italian Health Ministry and was held 9 times over 3 years. We had 425 attendees,
      but full data sets (with complete questionnaires) were available for 403
      physicians (55% women, age 45 +/- 6 years), including 55% cardiologists, 40%
      general practitioners, 5% others (mainly cardiology fellows). For each attendee,
      a radiological awareness score was obtained before and after the course, with a
      survey containing 10 multiple-choice questions (5 answers) on radioprotection
      basics (doses of common examinations in multiples of chest x-rays; associated
      cancer risk, etc.). Each answer was scored from 0 ("don't know"), 1 ("strongly
      disagree") to 4 ("strongly agree"). The radiological awareness score of the 403
      attendees improved from 31 +/- 3 (before) to 37 +/- 2 (after training, P < 0.001
      vs. pre-training). As an example, before training, 25% of attendees believed that
      radiation-induced cancer risk disappears after 6 months (10% of respondents), 12
      months (8%) or 5 years (7%), whereas 75% (becoming 98% after training) correctly
      estimated that radiological damage is cumulative over one's lifetime. Awareness
      of radiological doses and risks, albeit essential for risk-benefit assessment of
      radiological testing, is suboptimal among cardiologists, but can dramatically
      improve with a limited teaching effort through targeted training.

PMID- 21850412
TI  - Why did I start dialysis? A qualitative study on views and expectations from an
      elderly cohort of patients with end-stage renal failure starting haemodialysis in
      the United Kingdom.
AB  - BACKGROUND: It is now common for elderly patients with end-stage kidney disease
      to be offered treatment by dialysis. However, what these patients expect from
      dialysis is not known. Therefore, the purpose of this study was to elucidate the
      expectations of elderly patients starting dialysis and to investigate whether
      their views change after 6 months on this treatment. METHODS: This was a
      prospective observational qualitative study of patients commencing haemodialysis
      in our centre from 2006 to 2007. Data were collected by interview and review of
      case notes at the time of starting dialysis and after 6 months of treatment.
      Patients were asked about their expectations from dialysis, symptoms, and views
      on advance care planning. RESULTS: Data were collected from 22 patients (mean age
      69.1 years) within a month from starting dialysis. Seventy per cent of these
      patients had attended a pre-dialysis clinic for at least 4 months previously;
      despite this, many of the patients complained about having had little choice in
      starting dialysis and seemed uncertain about what dialysis would involve. Even
      so, over 90% of those interviewed were optimistic about dialysis, had high
      expectations from treatment and were not keen to discuss advance care planning at
      first interview. Sixteen patients were re-interviewed at 6 months (four patients
      had died meanwhile and two had been transferred to other centres). After 6
      months, there was a change in patients' attitude, with only 45% of them still
      finding dialysis acceptable and more patients now keen to discuss advance care
      planning. Symptom burden was higher at 6 months than at initiation of dialysis
      treatment. CONCLUSION: Most elderly patients have unrealistic expectations from
      dialysis at the start of treatment. There is a need for more specific counselling
      of these patients to ensure that they make informed decisions about treatment
      modality and have realistic expectations if they chose to receive RRT.

PMID- 21850413
TI  - A simple and efficient method for agroinfection of Vernonia cinerea with
      infectious clones of Vernonia yellow vein virus.
AB  - Vernonia yellow vein virus (VeYVV) is a distinct monopartite begomovirus
      associated with a satellite DNA beta. After constructing dimers of both DNA A and
      DNA beta in binary vectors, a number of infection methods were attempted.
      However, only a modified stem-prick method produced up to 83% infection in the
      natural host Vernonia cinerea, thus, fulfilling the Koch's postulate. The
      presence of the viral DNA in the agroinfected plants was confirmed by rolling
      circle amplification (RCA), followed by Southern hybridization. DNA beta induces
      typical symptoms of Vernonia yellow vein disease (VeYVD) when co-agroinoculated
      with the begomovirus to Vernonia and also leads to the accumulation of DNA A
      systemically. VeYVV represents a new member of the emerging group of monopartite
      begomoviruses requiring a satellite component for symptom induction.

PMID- 21850414
TI  - Arsenic mobility in the amended mine tailings and its impact on soil enzyme
      activity.
AB  - The objectives of this study were to elucidate the effects of soil amendments
      [Ferrous sulfate (Fe(II)), red mud, Fe(II) with calcium carbonate (Fe(II)/L) or
      red mud (RM/F), zero-valent iron (ZVI), furnace slag, spent mushroom waste and by
      product fertilizer] on arsenic (As) stabilization and to establish relationships
      between soil properties, As fractions and soil enzyme activities in amended As
      rich gold mine tailings (Kangwon and Keumkey). Following the application of
      amendments, a sequential extraction test and evaluation of the soil enzyme
      activities (dehydrogenase and beta-glucosidase) were conducted. Weak and negative
      relationships were observed between water-soluble As fractions (As(WS)) and
      oxalate extractable iron, while As(WS) was mainly affected by dissolved organic
      carbon in alkaline tailings sample (Kangwon) and by soil pH in acidic tailings
      sample (Keumkey). The soil enzyme activities in both tailings were mainly
      associated with As(WS). Principal component and multiple regression analyses
      confirmed that As(WS) was the most important factor to soil enzyme activities.
      However, with some of the treatments in Keumkey, contrary results were observed
      due to increased water-soluble heavy metals and carbon sources. In conclusion,
      our results suggest that to simultaneously achieve decreased As(WS) and increased
      soil enzyme activities, Kangwon tailings should be amended with Fe(II), Fe(II)/L
      or ZVI, while only ZVI or RM/F would be suitable for Keumkey tailings. Despite
      the limitations of specific soil samples, this result can be expected to provide
      useful information on developing a successful remediation strategy of As
      contaminated soils.

PMID- 21850415
TI  - Parathyroid gland anatomical distribution and relation to anthropometric and
      demographic parameters: a cadaveric study.
AB  - Parathyroid glands play an important role in controlling calcium levels, which
      influence muscular contraction and neurotransmission. The number of variants,
      localization and ectopic positions make these glands tricky during surgical
      exploration. Detailed anatomical knowledge of these glands is fundamental to
      avoid postsurgical hypoparathyroidism, such as failures during thyroidectomy and
      parathyroid procedures. The purposes of this work were to study and report
      practical knowledge for surgeons in order to localize the glands. Dissections
      were performed on 56 cadavers. Gland identity was confirmed by histological
      study. Also, mediastinal tissue and the carotid sheath were treated with Carnoy's
      solution to identify ectopic glands. The thyroid gland was divided and sliced to
      identify parathyroid glands in the parenchymal and subcapsular space. Four or
      more parathyroid glands were found in 89.3% of the studied specimens. Mean gland
      weight was 33.1 mg, and its mean measurements were 6.7 * 3.9 * 2.0 mm. In more
      than 90% of the cases there was a correlation with the inferior laryngeal nerve
      and the parathyroid glands: the upper glands were located in medial positions,
      and the lower ones were found to be located laterally. In 42.8% of cases at least
      one ectopic gland was observed. The main ectopic regions were the mediastinum and
      thymus (19.6%), thyroid subcapsular space (12.5%) and thyroid parenchyma (5.4%).
      Quantity, gland characteristics and location were not influenced by
      anthropometric and demographic parameters. Here we show the high incidence of
      parathyroid glands positioned at "abnormal" locations, and as a controversial
      topic in endocrine surgery, this matter must be continuously studied and reported
      in the literature.

PMID- 21850417
TI  - Development and validation of the simplified Chinese version of EORTC QLQ-H&N35
      for patients with head and neck cancer.
AB  - GOALS: A simplified Chinese version of EORTC QLQ-H&N35 was developed using strict
      translation procedures according to EORTC translation guidelines. Psychometric
      properties were evaluated. PATIENTS AND METHODS: Three instruments (QLQ-H&N35,
      QLICP-HN, and FACT-H&N) were used in a sample of 133 patients with head and neck
      cancer at the time of their admission to the hospital. Each patient was assessed
      for the second time 1-2 days after hospitalization so that the test-retest
      reliability could be calculated. A sub-sample of patients was sampled and
      measured for the third time at discharge in order to evaluate the responsiveness.
      RESULTS: Correlation analysis among domains and items of the three instruments
      showed good construct validity and criterion-related validity. Comparisons of QLQ
      H&N35 between treatment groups and age groups supported clinical validity. The
      internal consistency reliability measured by Cronbach's coefficient alpha was
      greater than 0.70 for all multi-item domains, and test-retest reliability
      coefficients for all domains were greater than 0.80, ranging from 0.88 to 0.95.
      Score changes between pre- and post-treatment were observed in 6 out of 18
      domains, with effect size SRM ranging from 0.27 to 0.87. CONCLUSIONS: The
      simplified Chinese version of QLQ-H&N35 demonstrates good validity, reliability,
      and responsiveness and can be used to measure QOL for Chinese patients with head
      and neck cancer.

PMID- 21850416
TI  - A pilot study of adrenal suppression after dexamethasone therapy as an antiemetic
      in cancer patients.
AB  - PURPOSE: Dexamethasone has a high therapeutic index when used to prevent
      chemotherapy-induced nausea and vomiting. However, the chronic use of
      glucocorticoids has been associated with suppression of the hypothalamic
      pituitary-adrenal axis. Therefore, the authors designed this pilot study to
      assess the incidence of adrenal insufficiency after dexamethasone therapy as an
      antiemetic in cancer patients receiving chemotherapy. METHODS: The rapid
      adrenocorticotropic hormone (ACTH) stimulation test was performed in 103 cancer
      patients, who had been treated with high-dose dexamethasone as an antiemetic for
      more than 3 months. When response to the rapid ACTH stimulation test was
      abnormal, the patient received corticosteroid replacement by prednisolone 7.5 mg
      daily for 1-2 weeks and after prednisolone replacement, changes in symptoms
      associated with adrenal insufficiency were investigated using a visual analog
      scale. RESULTS: Forty-five of the 103 patients (43.7%) showed a suppressed
      adrenal response to the rapid ACTH stimulation test, and the incidence of adrenal
      suppression was found to be significantly affected by megestrol acetate use (P =
      0.035). Thirty-three patients with a suppressed adrenal function achieved an
      improvement in quality of life after prednisolone replacement, as determined
      using a self-report questionnaire (22.9 +/- 14.7 to 14.8 +/- 11.0, P < 0.001).
      CONCLUSIONS: We suggest that suppression of adrenal response is common after
      antiemetic dexamethasone therapy in cancer patients receiving chemotherapy.

PMID- 21850418
TI  - Widespread use of neuraminidase inhibitors in Japan.
AB  - Almost all patients with an influenza-like illness in Japan are now tested with
      rapid diagnostic tests, and when positive, they are treated with a neuraminidase
      inhibitor (NAI). Japan may have had the lowest case fatality rate for symptomatic
      illness (<0.001%, 198/20.7 million) in the H1N1/09 pandemic because of the
      universal implementation of early treatment with NAI. A study of 1,000 children
      hospitalized because of a H1N1/09 infection revealed that NAIs, primarily
      oseltamivir, had been used to treat 984 (98.4%) of the 1,000 patients. In 88.9%
      of the patients, treatment with NAIs was initiated within 48 h after the onset of
      illness. In addition to oseltamivir and zanamivir, the newly approved inhalant
      drug, laninamivir, and the newly approved intravenous drug, peramivir, were used
      in Japan during the 2010-2011 season. Neuropsychiatric disorders that were
      suspected of being adverse reactions to oseltamivir became a cause of concern in
      2007. The Health, Labour and Welfare Ministry issued an emergency instruction to
      suspend the use of oseltamivir to treat patients between the ages of 10 and 19
      years. However, according to the Vital Statistics data, the widespread use of
      oseltamivir has not caused an increase in deaths as a result of accidental falls
      or intentional jumps from buildings. Although oseltamivir is widely used in
      Japan, no outbreaks have been caused by oseltamivir-resistant viruses, and no
      serious illness caused by oseltamivir-resistant viruses has ever been reported.

PMID- 21850419
TI  - Initiation and progression of ossification of the posterior longitudinal ligament
      of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy).
AB  - INTRODUCTION: Ossification of the posterior longitudinal ligament (OPLL) is a
      significantly critical pathology that can eventually cause serious myelopathy.
      Ossification commences in the vertebral posterior longitudinal ligaments, and
      intensifies and spreads with the progression of the disease, resulting in osseous
      projections and compression of the spinal cord. However, the paucity of
      histological studies the underlying mechanisms of calcification and ossification
      processes remain obscure. The pathological process could be simulated in the
      ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy).
      The aim of this study is to observe that enlargement of the nucleus pulposus
      followed by herniation, disruption and regenerative proliferation of annulus
      fibrosus cartilaginous tissues participated in the initiation of ossification of
      the posterior longitudinal ligament of twy/twy mice. MATERIALS AND METHODS: The
      mutant twy/twy mice (6 to 22-week-old) were used in the present study. The
      vertebral column was analyzed histologically and immunohistochemically. RESULTS:
      We observed that the enlargement of the nucleus pulposus followed by herniation,
      disruption and regenerative proliferation of annulus fibrosus cartilaginous
      tissues participated in the initiation of ossification of posterior longitudinal
      ligament of twy/twy mice. In this regards, the cells of the protruded
      hyperplastic annulus fibrosus invaded the longitudinal ligaments and induced
      neovascularization and metaplasia of primitive mesenchymal cells to osteoblasts
      in the spinal ligaments of twy/twy mice. CONCLUSION: Since genetic mechanisms
      could play a role in human OPLL, the age-related enlargement of the nucleus
      pulposus in the twy/twy mouse may primarily occur as a result of overproduction
      of mucopolysaccharide matrix material induced by certain genetic abnormalities.

PMID- 21850420
TI  - GEER, the Multidisciplinary Spanish Society for Spine Specialists.

PMID- 21850421
TI  - Instrumented lumbar arthrodesis in elderly patients: prospective study using
      cannulated cemented pedicle screw instrumentation.
AB  - INTRODUCTION: Lumbar fusion in elderly patients is increasingly common. This
      study prospectively investigated the clinical and radiological outcome of
      osteoporotic patients >70 years with degenerative lumbar instability treated with
      fusion using a new cannulated, cemented, pedicle screw instrumentation augmented
      with PMMA. MATERIALS AND METHODS: The surgical protocols, patient records,
      densitometry, imaging studies, and pre- and postoperative patient-reported
      outcome questionnaires of 23 patients (mean age, 77 years) with a follow-up of 20
      49 months were reviewed. All patients underwent postoperative 3D CT scan control
      to assess cement leakage and instrumentation position. Serial radiological
      controls were analyzed for secondary complications, i.e., adjacent fractures,
      hardware mobilization and radiological evidence of fusion. RESULTS: Pain and
      function improved at 6 months and were maintained at the final follow-up. No
      clinical complications secondary to PMMA leakage developed. No clinical or
      radiological cases of non-union were observed with a mean of 1.8 levels fused. No
      fractures occurred in adjacent segments. There were four cases of adjacent disc
      disease. Three deep infections required surgical revision without removal of
      material and one superficial infection, all with complete remission. CONCLUSION:
      This new instrumentation for degenerative lumbar disease in elderly patients is
      safe and effective.

PMID- 21850422
TI  - Age-related effects of fasting on ketone body production during lipolysis in
      rats.
AB  - OBJECTIVE: The age-related effects of fasting on lipolysis, the production of
      ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week
      old Sprague-Dawley rats. METHODS: The rats were divided into fasting and control
      groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12 days,
      respectively. RESULTS: Fasting markedly reduced the weights of perirenal and
      periepididymal white adipose tissues in rats in the three age groups. The mean
      rates of reduction in both these adipose tissue weights during fasting periods
      were higher in the order of 3 > 8 > 32-week-old rats. Fasting transiently
      increased plasma free fatty acid (FFA), total ketone body, beta-hydroxybutyrate,
      and acetoacetate concentrations in the rats in the three age groups. However,
      plasma FFA, total ketone body, beta-hydroxybutyrate, and acetoacetate
      concentrations in the 3-week-old rats reached maximal peak within 2 days after
      the onset of fasting, although these concentrations in the 8- and 32-week-old
      rats took more than 2 days to reach the maximal peak. By contrast, the
      augmentation of plasma FFA, total ketone body, beta-hydroxybutyrate, and
      acetoacetate concentrations in the rats in the three age groups had declined at
      the end of each experimental period. Thus, the capacity for fat mobilization was
      associated with tolerance to fasting. Plasma insulin concentrations in the rats
      in the three age groups were dramatically reduced during fasting periods,
      although basal levels of insulin were higher in the order of 32 > 8 > 3 week-old
      rats. CONCLUSION: These results suggest that differences in fat metabolism
      patterns among rats in the three age groups during prolonged fasting were partly
      reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat
      storage.

PMID- 21850423
TI  - A chemiluminescence sensor array for discriminating natural sugars and artificial
      sweeteners.
AB  - In this paper, we report a chemiluminescence (CL) sensor array based on catalytic
      nanomaterials for the discrimination of ten sweeteners, including five natural
      sugars and five artificial sweeteners. The CL response patterns ("fingerprints")
      can be obtained for a given compound on the nanomaterial array and then
      identified through linear discriminant analysis (LDA). Moreover, each pure
      sweetener was quantified based on the emission intensities of selected sensor
      elements. The linear ranges for these sweeteners lie within 0.05-100 mM, but vary
      with the type of sweetener. The applicability of this array to real-life samples
      was demonstrated by applying it to various beverages, and the results showed that
      the sensor array possesses excellent discrimination power and reversibility.

PMID- 21850425
TI  - Pregabalin: a treatment option for dystonia?
AB  - To date, no studies are available on the effect of pregabalin in dystonia. A
      patient with subarachnoidal and cerebral hemorrhage was treated with pregabalin
      for neuropathic pain. Upon withdrawal of the medication she experienced
      spontaneous and painful supination in the right foot and internal hip rotation
      when standing up. When pregabalin was reinstituted, these dystonic symptoms
      subsided, but reappeared when the medication was again discontinued. One possible
      explanation for these symptoms could be neuronal hyperactivity within still
      functioning pathways in connection with the motor cortex. Preponderance of
      activity in potentially compensatory structures could be suppressed by
      pregabalin: therefore, its potential benefit in subacute secondary dystonia in
      cases with orbital brain involvement is suggested.

PMID- 21850424
TI  - Nitric oxide signaling in aluminum stress in plants.
AB  - Nitric oxide (NO) is a ubiquitous signal molecule involved in multiple plant
      responses to environmental stress. In the recent years, the regulating role of NO
      on heavy metal toxicity in plants is realized increasingly, but knowledge of NO
      in alleviating aluminum (Al) toxicity is quite limited. In this article, NO
      homeostasis between its biosynthesis and elimination in plants is presented. Some
      genes involved in NO/Al network and their expressions are also introduced.
      Furthermore, the role of NO in Al toxicity and the functions in Al tolerance are
      discussed. It is proposed that Al toxicity may disrupt NO homeostasis, leading to
      endogenous NO concentration being lower than required for root elongation in
      plants. There are many evidences that pointed out that the exogenous NO
      treatments improve Al tolerance in plants through activating antioxidative
      capacity to eliminate reactive oxygen species. Most of the work with respect to
      NO regulating pathways and functions still has to be done in the future.

PMID- 21850426
TI  - A case of hypertensive intraventricular hemorrhage bled from the hippocampus.
AB  - The hippocampus is not a usual origin of bleeding due to hypertension. A 66-year
      old male suffered from headache and abnormal behavior. Computed tomographic
      images showed an intraventricular hemorrhage predominantly located in the right
      lateral ventricle. His arterial blood pressure was 198/92 mmHg on admission. No
      apparent vascular anomaly was demonstrated on a digital subtraction angiogram.
      Two months after the onset, his mini-mental status examination showed full
      recovery from the score of 19 at onset, and most of his memory disturbances were
      improved except for visual memory disturbance. A follow-up magnetic resonance
      image revealed that the hemosiderin was stained in the atrophic right
      hippocampus, and the final diagnosis was hypertensive intraventricular hemorrhage
      bled from the right hippocampus. It is difficult to diagnose hippocampal
      hemorrhage immediately when it is combined with intraventricular hemorrhage,
      because the hippocampus is covered with hematoma in the inferior horn. Moreover,
      with regard to neurologic examination, the patients do not show any focal sign
      such as hemiparesis or aphasia. In elderly patients with compensatory ventricular
      dilatation, one must also be attentive to a misdiagnosis of obstructive
      hydrocephalus due to intraventricular hemorrhage.

PMID- 21850427
TI  - Analytic cognitive style in cluster headache.
AB  - Previous reports on cluster headache have shown a hypothalamic dysfunction and a
      hitherto unrecognized defect in the information processing pathways measured by
      event-related potentials. As of today, the causes are still unknown; likewise,
      studies on the psychological factors involved in CH have not yielded relevant
      data. The aim of our study was to evaluate the presence of a possible correlation
      between CH and a specific manner of information processing, i.e., an analytic
      cognitive style. This study applies two cognitive style tests that have not
      previously been used in the context of cluster headache: "Sternberg-Wagner Self
      Assessment Inventory" and the C. Cornoldi AMOS test series. Twenty-three CH
      patients were involved in the study and were compared with two control groups:
      healthy subjects and tension type headache patients. Our findings clearly
      indicate a significant correlation between analytic cognitive style and CH,
      warranting further studies focusing on the underlying neurophysiological
      mechanisms.

PMID- 21850428
TI  - ACL reconstruction: comparison between transtibial and anteromedial portal
      techniques.
AB  - PURPOSE: The purpose of this study was to compare the transtibial reconstruction
      technique of the anterior cruciate ligament (ACL) with the anteromedial (AM)
      portal technique in their ability to place the femoral and tibial tunnels within
      the ACL footprints. METHODS: Forty patients were sequentially enrolled in two
      different surgical techniques, 20 patients in the transtibial and 20 patients in
      the AM portal technique. All patients underwent computed tomography scan of the
      operated knee. The center of the femoral tunnel aperture on the lateral femoral
      condyle was measured according to the quadrant method. On the tibial side, the
      center of the tibial tunnel was measured in the sagittal plane. These
      measurements were compared with the center of the normal AM and PL bundles.
      RESULTS: There were no differences in the center of the femoral tunnels on the
      Blumensaat's line between the two groups (mean 23.5% (4.2) for the transtibial
      technique and 26.0% (4.3) for the AM portal technique (P = n.s.). In the height
      of the femoral condyle, the center of the tunnels was significantly lower in the
      AM portal technique group [mean 34.7% (3.8) vs. 24.0% (7.9) (P < 0.001)]. In the
      tibia, the center of the tunnel in the sagittal plane was significantly posterior
      in the transtibial technique (mean 55.4% (4.9) vs. 44.4% (3.7) (P < 0.001).
      CONCLUSIONS: The AM portal technique places the femoral and tibial tunnels more
      centrally in the ACL footprint when compared with the transtibial technique.
      LEVEL OF EVIDENCE: II.

PMID- 21850430
TI  - Effect of mercaptocarboxylic acids on luminescent properties of CdTe quantum
      dots.
AB  - CdTe quantum dots (QDs) were prepared in an aqueous solution using various
      mercaptocarboxylic acids, such as 3-mercaptopropionic acid (MPA) and thioglycolic
      acid (TGA), as stabilizing agents. The experimental result indicated that these
      stabilizing agents played an important role for the properties of the QDs.
      Although both TGA and MPA-capped CdTe QDs exhibited the tunable photoluminescence
      (PL) from green to red color, the TGA-capped QDs revealed a higher PL quantum
      yield (QY) up to 60% than that of MPA-capped QDs (up to 50%) by using the optimum
      preparation conditions, such as a pH value of ~11.2 and a TGA/Cd molar ratio of
      1.5. PL lifetime measurements indicate that the TGA-capped QDs exhibited a short
      average lifetime while the MPA-capped QDs revealed a long one. Furthermore, the
      average lifetime of the TGA-capped QDs increased with the increase of the QDs
      size, while a decreased lifetime for the MPA-capped QDs was obtained. This means
      that the PL lifetime depended strongly on the surface state of the CdTe QDs.
      These results should be utilized for the preparation and applications of QDs.

PMID- 21850429
TI  - Optimal measurement of clinical rotational test for evaluating anterior cruciate
      ligament insufficiency.
AB  - PURPOSE: Rotational instability in ACL insufficient knee addresses the symptom or
      the abnormal motion which can be reproduced and subjectively evaluated in the
      clinical exam. Clinically available quantitative measurement for this instability
      has not been established due to mixed testing maneuvers and complex kinematics.
      The purpose was to measure knee kinematics during three manually performed
      rotational tests and to determine the optimal method to detect the abnormality in
      ACL deficient knees. METHOD: Thirteen unilateral ACL deficient patients were
      tested by internal and external pure rotational stress tests and pivot shift test
      under anesthesia before scheduled ACL reconstructions. Rotation and coupled
      motion, i.e., tibial anteroposterior translation, were measured using an
      electromagnetic measurement system. Additionally, the acceleration of the tibial
      posterior translation during pivot shift test was calculated. The differences of
      these parameters between ACL intact and deficient knees were tested. RESULTS:
      Knee rotation is not different between ACL intact and deficient during both pure
      rotational stress test and pivot shift test. The coupled anterior tibial
      translation during pivot shift test was significantly different between ACL
      intact, 13.5 +/- 4.1 mm, and deficient knees, 23.1 +/- 4.4 mm, (P < 0.01) as well
      as the acceleration of the tibial posterior translation (1.1 +/- 0.4 m/sec(2) in
      intact knees, 3.2 +/- 1.5 m/sec(2) in deficient knees; P < 0.01). The coupled
      motion during pure rotational stress tests was similar regardless of ACL
      condition. CONCLUSION: The rotational instability of the ACL deficiency was
      reproduced only by the pivot shift test and detected only by measuring the tibial
      anteroposterior translation and acceleration of the tibial posterior reduction.
      Level of evidence Diagnostic study, Level III.

PMID- 21850431
TI  - Identification, cloning, and characterization of beta-glucosidase from Ustilago
      esculenta.
AB  - Hydrolytic enzymes responsible for laminarin degradation were found to be
      secreted during growth of Ustilago esculenta on laminarin. An enzyme involved in
      laminarin degradation was purified by assaying release of glucose from
      laminaribiose. Ion-exchange chromatography of the culture filtrate followed by
      size-exclusion chromatography yielded a 110-kDa protein associated with
      laminaribiose hydrolysis. LC/MS/MS analysis of the 110-kDa protein identified
      three peptide sequences that shared significant similarity with a putative
      glucoside hydrolase family (GH) 3 beta-glucosidase in Ustilago maydis. Based on
      the DNA sequence of the U. maydis GH3 beta-glucosidase, a gene encoding a
      putative GH3 beta-glucosidase in U. esculenta (Uebgl3A) was cloned by PCR. Based
      on the deduced amino acid sequence, the protein encoded by Uebgl3A has a
      molecular mass of 91 kDa and shares 90% identity with U. maydis GH3 beta
      glucosidase. Recombinant UeBgl3A expressed in Aspergillus oryzae released glucose
      from beta-1,3-, beta-1,4-, and beta-1,6-linked oligosaccharides, and from 1,3-1,4
      beta-glucan and laminarin polysaccharides, indicating that UeBgl3A is a beta
      glucosidase. Kinetic analysis showed that UeBgl3A preferentially hydrolyzed
      laminaritriose and laminaritetraose. These results suggest that UeBgl3A is a key
      enzyme that produces glucose from laminarioligosaccharides during growth of U.
      esculenta on laminarin.

PMID- 21850432
TI  - Analysis of heterologous taxadiene production in K- and B-derived Escherichia
      coli.
AB  - Taxa-4(5),11(12)-diene is the first dedicated intermediate in the metabolic
      pathway responsible for synthesizing the anticancer compound Taxol. In this
      study, the heterologous production of taxadiene was established in and analyzed
      between K- and B-derived Escherichia coli strains. First, recombinant parameters
      associated with precursor metabolism (the upstream methylerythritol phosphate
      (MEP) pathway) and taxadiene biosynthesis (the downstream pathway) were varied to
      probe the effect different promoters and cellular backgrounds have on taxadiene
      production. Specifically, upstream MEP pathway genes responsible for the
      taxadiene precursors, dimethylallyl diphosphate and isopentenyl diphosphate, were
      tested with an inducible T7 promoter system within K and B E. coli strains.
      Whereas, inducible T7, Trc, and T5 promoters were tested with the plasmid-borne
      geranylgeranyl diphosphate synthase and taxadiene synthase genes responsible for
      the downstream pathway. The K-derivative produced taxadiene roughly 2.5-fold
      higher than the B-derivative. A transcriptomics study revealed significant
      differences in pyruvate metabolism between the K and B strains, providing insight
      into the differences observed in taxadiene biosynthesis and targets for future
      metabolic engineering efforts. Next, the effect of temperature on cell growth and
      taxadiene production was analyzed in these two strains, revealing similar
      phenotypes between the two with 22 degrees C as the optimal production
      temperature. Lastly, the effect of indole on cell growth was investigated between
      the two strains, showing that the K-derivative demonstrated greater growth
      inhibition compared to the B-derivative.

PMID- 21850433
TI  - Laccase-catalysed protein-flavonoid conjugates for flax fibre modification.
AB  - The introduction of flavonoid compounds into proteins can improve the natural
      properties of proteins, being promising products which essentially require
      antioxidant property. The oxidative conjugation of protein-flavonoids was
      processed by laccase catalysis resulting in the synthesis of biologically
      functional polymers. The new reaction products were detected in terms of sodium
      dodecyl sulfate polyacrylamide gel electrophoresis and matrix-assisted laser
      desorption/ionisation-time of flight mass spectra, showing a greater molecular
      weight formation. Their characterisations were further carried out in terms of UV
      Vis spectroscopy, photon correlation spectroscopy, differential scanning
      calorimetry and Fourier transform infrared (FT-IR) spectroscopy analysis. In
      addition, their application of protein-flavonoid conjugates onto flax fibres was
      exploited to supplement a suitable microorganism environment of protein-possessed
      fibres. The anchoring of conjugates onto cationised fibres was successfully
      performed by ionic interaction with negatively charged proteins. The level of
      anchoring efficiency was quantified in terms of measuring colour strength (k/s)
      and fluorescence microscopy analysis. The conjugates onto fibres presented
      acceptable durability in terms of washing resistance and the surface became
      hydrophilic when alpha-casein-catechin was applied (lower contact angle 48
      degrees ). By the anchoring of protein-flavonoid conjugates onto flax fibres, the
      final products with new colour generation and antioxidant activity (>93%) were
      obtained.

PMID- 21850434
TI  - Groundwater quality and its suitability for domestic and agricultural use in
      Tondiar river basin, Tamil Nadu, India.
AB  - Assessment of suitability of groundwater for domestic and agricultural purposes
      was carried out in Tondiar river basin, Tamil Nadu, India. The study area covers
      an area of 315 km(2) and lies in a semiarid region. Groundwater is the major
      source for domestic and agricultural activity in this area. Groundwater samples
      were collected from 45 wells during pre-monsoon and post-monsoon period in the
      year 2006. The water samples were analysed for physical and chemical
      characteristics. Suitability of groundwater for irrigation was evaluated based on
      salinity hazard, sodium percent, sodium adsorption ratio, residual sodium
      carbonate, US salinity diagram, Wilcox's diagram, Kelly's ratio and permeability
      index. Ca-HCO(3), mixed Ca-Mg-Cl and Na-Cl were the dominant groundwater types.
      High hardness and electrical conductivity in this area makes the groundwater
      unsuitable for drinking and agricultural purposes. Concentration of trace
      elements (Mn, Cu, Zn, Pb and Ni) did not exceed the permissible limit for
      drinking and agricultural purposes. Majority of the groundwater samples were
      unsuitable for domestic and agricultural purposes except for 31% and 36%, which
      were suitable for drinking and irrigation purposes, respectively.

PMID- 21850435
TI  - Functional impairment in Latino children with ADHD: implications for culturally
      appropriate conceptualization and measurement.
AB  - Conceptualizing and measuring functional impairment related to childhood ADHD,
      particularly within the rapidly growing, yet underserved, Latino population, is
      an important area of research that is in its infancy in the field of psychology.
      The functional impairments related to academic achievement, social competence,
      and familial relations experienced by children with ADHD lead to long-lasting and
      debilitating difficulties that adversely affect the individuals themselves, their
      families, and society. In addition, limited available research suggests that
      Latino children are at a great or greater risk for developing ADHD, although they
      are much less likely to be identified by their parents as displaying problematic
      behavior and subsequently are less likely to receive proper assessment and
      treatment due to several practical and cultural factors. Fortunately, initial
      evidence suggests that the construct of functional impairment may be a more
      universal notion than the potentially culturally biased measurement of
      symptomatology. Therefore, in order to provide the best possible outcomes for all
      children with ADHD, research needs to be expanded to include examination of
      functional impairment related to ADHD, particularly when working with Latino
      children and their families. Thus, the primary aim of the current review is to
      examine and critique how the field of psychology has understood and measured
      functional impairment in school-aged Latino children with ADHD to date. Based on
      information reviewed, suggestions for moving toward a culturally modified
      assessment of functional impairment related to ADHD in Latino children will be
      proposed. This work is a necessary step toward providing culturally appropriate
      services for a currently underserved, yet rapidly growing, Latino population in
      our country.

PMID- 21850436
TI  - Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic
      development.
AB  - The eukaryotic initiation factor 5A (eIF5A) contains a polyamine-derived amino
      acid, hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. Hypusine is formed
      post-translationally by the addition of the 4-aminobutyl moiety from the
      polyamine spermidine to a specific lysine residue, catalyzed by deoxyhypusine
      synthase (DHPS), and subsequent hydroxylation by deoxyhypusine hydroxylase
      (DOHH). The eIF5A precursor protein and both of its modifying enzymes are highly
      conserved, suggesting a vital cellular function for eIF5A and its hypusine
      modification. To address the functions of eIF5A and the first modification
      enzyme, DHPS, in mammalian development, we knocked out the Eif5a or the Dhps gene
      in mice. Eif5a heterozygous knockout mice and Dhps heterozygous knockout mice
      were viable and fertile. However, homozygous Eif5a1 (gt/gt) embryos and Dhps
      (gt/gt) embryos died early in embryonic development, between E3.5 and E7.5. Upon
      transfer to in vitro culture, homozygous Eif5a (gt/gt) or Dhps (gt/gt)
      blastocysts at E3.5 showed growth defects when compared to heterozygous or wild
      type blastocysts. Thus, the knockout of either the eIF5A-1 gene (Eif5a) or of the
      deoxyhypusine synthase gene (Dhps) caused early embryonic lethality in mice,
      indicating the essential nature of both eIF5A-1 and deoxyhypusine synthase in
      mammalian development.

PMID- 21850437
TI  - Prediction of membrane proteins using split amino acid and ensemble
      classification.
AB  - Knowledge of the types of membrane protein provides useful clues in deducing the
      functions of uncharacterized membrane proteins. An automatic method for
      efficiently identifying uncharacterized proteins is thus highly desirable. In
      this work, we have developed a novel method for predicting membrane protein types
      by exploiting the discrimination capability of the difference in amino acid
      composition at the N and C terminus through split amino acid composition (SAAC).
      We also show that the ensemble classification can better exploit this
      discriminating capability of SAAC. In this study, membrane protein types are
      classified using three feature extraction and several classification strategies.
      An ensemble classifier Mem-EnsSAAC is then developed using the best feature
      extraction strategy. Pseudo amino acid (PseAA) composition, discrete wavelet
      analysis (DWT), SAAC, and a hybrid model are employed for feature extraction. The
      nearest neighbor, probabilistic neural network, support vector machine, random
      forest, and Adaboost are used as individual classifiers. The predicted results of
      the individual learners are combined using genetic algorithm to form an ensemble
      classifier, Mem-EnsSAAC yielding an accuracy of 92.4 and 92.2% for the Jackknife
      and independent dataset test, respectively. Performance measures such as MCC,
      sensitivity, specificity, F-measure, and Q-statistics show that SAAC-based
      prediction yields significantly higher performance compared to PseAA- and DWT
      based systems, and is also the best reported so far. The proposed Mem-EnsSAAC is
      able to predict the membrane protein types with high accuracy and consequently,
      can be very helpful in drug discovery. It can be accessed at
      http://111.68.99.218/membrane.

PMID- 21850438
TI  - Glutamate carboxypeptidase II (GCPII) inhibitor displays anti-glutamate and anti
      cocaine effects in an invertebrate assay.
AB  - Glutamate carboxypeptidase II (GCPII) inhibitors are promising anti-glutamatergic
      and anti-addictive agents. We hypothesized that a GCPII inhibitor 2
      (phosphonomethyl) pentanedioic acid (2-PMPA) would display anti-stereotypical
      activity in planarians. Experiments revealed that 2-PMPA displayed no overt
      behavioral activity by itself but attenuated stereotypical counts (C-shape
      hyperkinesias) elicited by four compounds (2-PMPA rank order potency:
      glutamate>NMDA>pilocarpine>cocaine). These data suggest GCPII inhibitors display
      broad-spectrum efficacy against behavioral activity produced by glutamatergic and
      non-glutamatergic compounds in an invertebrate assay.

PMID- 21850439
TI  - Retinal vascular occlusion after vitrectomy with retrobulbar anesthesia
      observational case series and survey of literature.
AB  - BACKGROUND: Severe postoperative loss of vision has been occasionally reported as
      a rare complication of retrobulbar anesthesia, and several possible causes have
      been proposed in the literature. In this work, our own and other investigators'
      experiences with these complications are surveyed with a view to identifying its
      pathophysiology. PATIENTS: This observational case series refers to six patients
      who presented during a 3-month period with occlusion of either the central artery
      itself (n = 3) or a branch thereof (n = 3) 2-14 days after uneventful
      vitreoretinal surgery following retrobulbar anesthesia with a commercial
      preparation of mepivacaine (1% Scandicain(r), Astra Chemicals, Sweden) containing
      methyl- and propyl parahydroxybenzoate as preservatives. RESULTS: Three of the
      patients carried risk factors, which were medically controlled. In three
      individuals, vasoocclusion was observed after a second vitreoretinal
      intervention, which was performed 3-12 months after uneventful primary surgery.
      Good visual recovery was observed in only one instance. CONCLUSIONS: In patients
      who were anesthetized with preservative-free mepivacaine, no vasoocclusion
      occurred. In individuals who were anesthetized with mepivacaine containing the
      preservatives methyl- and propyl parahydroxybenzoate, a tenfold increase in the
      incidence of eyes requiring re-operation was documented, with a 2- to 14-day
      lapse in the onset of vasoocclusion. These findings reveal a possible implication
      of preservatives contained in the local anesthetic solution for the vasoocclusive
      events. Due to this potential hazard, the use of preservative-free preparations
      of local anesthesia in ocular surgery is emphasized in order to prevent this
      sight-threatening complication.

PMID- 21850440
TI  - Effect of 1-year lutein supplementation on macular pigment optical density and
      visual function.
AB  - BACKGROUND: Although it is known that antioxidants including lutein can affect
      macular pigment optical density (MPOD) and visual function, we still have much to
      learn about their effect. Our aim was to assess the 1-year changes in MPOD and
      visual function in response to supplementation containing lutein. METHODS: We
      prospectively measured the MPOD level of those who received a supplement
      containing 6 mg of lutein daily for 1 year. MPOD level was measured every 3
      months by using autofluorescence spectrometry with the two-wavelength method.
      Other examinations, including contrast sensitivity and retinal sensitivity were
      also measured every 3 or 6 months. Stepwise regression analysis was performed to
      determine the factors that correlated with the changes observed in those
      examinations. RESULTS: Forty-three eyes of 43 Japanese subjects, including five
      normal eyes, five fellow eyes with central serous chorioretinopathy (CSC), and 33
      fellow eyes with age-related macular degeneration (AMD) were enrolled. The higher
      baseline MPOD level was correlated with the eye with a clear intraocular lens
      (IOL). Although no time-dependent changes in the MPOD level were obtained in any
      area, subjects without cardiovascular diseases showed higher increase in the MPOD
      level. We observed significant increases in the contrast sensitivity at 1 year (p
      = 0.0124) and in the retinal sensitivity at 6 months (p < 0.0001) and 1 year (p <
      0.0001). Stepwise regression analysis showed that nonsmokers had increased
      contrast sensitivity (p = 0.0173), and the fellow eye of those with CSC had less
      of an increase in retinal sensitivity (p = 0.0491). CONCLUSIONS: Daily
      supplementation with 6 mg of lutein did not affect the MPOD level for 1 year,
      suggesting that 6 mg of lutein may be insufficient to increase the MPOD level.
      However, supplementation seems to improve visual functions such as contrast
      sensitivity and retinal sensitivity.

PMID- 21850441
TI  - Aged garlic extract attenuates cerebral damage and cyclooxygenase-2 induction
      after ischemia and reperfusion in rats.
AB  - Different garlic products reduce the cerebral ischemic damage due to their
      antioxidant properties. In this work, we investigated the effect of aged garlic
      extract (AGE) on cyclooxygenase-2 (COX-2) protein levels and activity, and its
      role as a possible mechanism of neuroprotection in a cerebral ischemia model.
      Animals were subjected to 1 h of ischemia plus 24 h of reperfusion. AGE (1.2
      ml/kg weight, i.p.) was administered at onset of reperfusion. To evaluate the
      damage induced by cerebral ischemia, the neurological deficit, the infarct area,
      and the histological alterations were measured. As an oxidative stress marker to
      deoxyribonucleic acid, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were
      determined. Finally, as inflammatory markers, TNFalpha levels and COX-2 protein
      levels and activity were measured. AGE treatment diminished the neurological
      alterations (61.6%), the infarct area (54.8%) and the histological damage (37.7%)
      induced by cerebral ischemia. AGE administration attenuated the increase in 8
      OHdG levels (77.8%), in TNFalpha levels (76.6%), and in COX-2 protein levels
      (73.6%) and activity (30.7%) induced after 1 h of ischemia plus 24 h of
      reperfusion. These data suggest that the neuroprotective effect of AGE is
      associated not only to its antioxidant properties, but also with its capacity to
      diminish the increase in TNFalpha levels and COX-2 protein expression and
      activity. AGE may have the potential to attenuate the cerebral ischemia-induced
      inflammation.

PMID- 21850442
TI  - Sticking to it: the effect of maximally assisted therapy on antiretroviral
      treatment adherence among individuals living with HIV who are unstably housed.
AB  - Housing is a known determinant of health behaviors, which includes adherence to
      Antiretroviral Therapy (ART). Within the Longitudinal Investigations into
      Supportive and Ancillary Health Services (LISA) study, unstable housing is
      inversely associated with adherence. Several comprehensive adherence support
      services have emerged to improve adherence for unstably housed or otherwise
      vulnerable populations. The Maximally Assisted Therapy (MAT) program in
      Vancouver, British Columbia uses a multidisciplinary approach to support HIV
      positive clients with a history of addictions or mental illness, many of whom
      also experience episodic homelessness. This study investigated the association
      between antiretroviral adherence and use of support services, including the MAT
      program, amongst people living with HIV and AIDS who are unstably housed in the
      LISA sample. Of the 212 unstably housed participants, those who attended the MAT
      program were 4.76 times more likely to be >=95% adherent (95% CI 1.72-13.13; P =
      0.003) than those who did not. The findings suggest that in the absence of
      sustainable housing solutions, programs such as MAT play an important role in
      supporting treatment adherence in this population.

PMID- 21850443
TI  - Behavioral surveillance study: sexual risk taking behaviour in UK HIV outpatient
      attendees.
AB  - This study aimed to determine demographic, behavioural and self-report
      disease/treatment variables among HIV-infected individuals (n = 666) that predict
      unprotected intercourse with a partner of unknown/discordant status. Sexual risk
      behaviour was reported by 12.8%. In multivariable analysis, risk was more likely
      to be reported by gay men compared to women or heterosexual men, and for those
      with higher psychological symptom burden. Psychological symptoms should be
      assessed and managed in the HIV outpatient setting to ensure integrated care that
      enhances prevention.

PMID- 21850444
TI  - Genetic approaches to understanding the causes of stuttering.
AB  - Stuttering is a common but poorly understood speech disorder. Evidence
      accumulated over the past several decades has indicated that genetic factors are
      involved, and genetic linkage studies have begun to identify specific chromosomal
      loci at which causative genes are likely to reside. A detailed investigation of
      one such region on chromosome 12 has identified mutations in the GNPTAB gene that
      are associated with stuttering in large families and in the general population.
      Subsequent studies identified mutations in the functionally related GNPTG and
      NAGPA genes. Mutations in these genes disrupt the lysosomal targeting pathway
      that generates the Mannose 6-phosphate signal, which directs a diverse group of
      enzymes to their target location in the lysosome of the cell. While mutations in
      these three genes can be identified in less than 10% of cases of familial
      stuttering, this knowledge allows a variety of new studies that can help identify
      the neuropathology that underlies this disorder.

PMID- 21850447
TI  - Induction and resuscitation of the viable but nonculturable state in a
      cyanobacteria-lysing bacterium isolated from cyanobacterial bloom.
AB  - The viable but nonculturable (VBNC) state has been found to be a growth strategy
      used by many aquatic pathogens; however, few studies have focused on VBNC state
      on other aquatic bacterial groups. The purpose of this study was to explore the
      VBNC state of cyanobacteria-lysing bacteria and the conditions that regulate
      their VBNC state transformation. Three cyanobacteria-lysing heterotrophic
      bacterial strains (F1, F2 and F3) were isolated with liquid infection method from
      a lake that has experienced a cyanobacterial bloom. According to their
      morphological, physiological and biochemical characteristics and results of
      16SrDNA sequence analysis, F1, F2 and F3 were identified as strains of
      Staphylococcus sp., Stappia sp. and Microbacterium sp., respectively. After being
      co-cultured with the axenic cyanobacterium, Microcystis aeruginosa 905, for 7
      days, strains F1, F2 and F3 exhibited an inhibition effect on cyanobacterial
      growth, which was expressed as a reduction in chlorophyll concentration of 96.0%,
      94.9% and 84.8%, respectively. Both autoclaved and filtered bacterial cultures
      still showed lytic effects on cyanobacterial cells while centrifuged pellets were
      less efficient than other fractions. This indicated that lytic factors were
      extracelluar and heat-resistant. The environmental conditions that could induce
      the VBNC state of strain F1 were also studied. Under low temperature (4 degrees
      C), distilled deionized water (DDW) induced almost 100% of F1 cells to the VBNC
      state after 6 days while different salinities (1%, 3% and 5% of NaCl solution)
      and lake water required 18 days. A solution of the cyanobacterial toxin
      microcystin-LR (MC-LR) crude extract also induced F1 to the VBNC state, and the
      effect was stronger than DDW. Even the lowest MC-LR concentration (10 MUg L(-1))
      could induce 69.7% of F1 cells into VBNC state after 24 h. On the other hand,
      addition of Microcystis aeruginosa cells caused resuscitation of VBNC state F1
      cells within 1 day, expressed as an increase of viable cell number and a decrease
      of VBNC ratio. Both VBNC state and culturable state F1 cells showed lytic effects
      on cyanobacteria, with their VBNC ratio varying during co-culturing with
      cyanobacteria. The findings indicated that VBNC state transformation of
      cyanobacteria-lysing bacteria could be regulated by cyanobacterial cells or their
      toxin, and the transformation may play an important role in cyanobacterial
      termination.

PMID- 21850446
TI  - Common features of environmental and potentially beneficial plant-associated
      Burkholderia.
AB  - The genus Burkholderia comprises more than 60 species isolated from a wide range
      of niches. Although they have been shown to be diverse and ubiquitously
      distributed, most studies have thus far focused on the pathogenic species due to
      their clinical importance. However, the increasing number of recently described
      Burkholderia species associated with plants or with the environment has
      highlighted the division of the genus into two main clusters, as suggested by
      phylogenetical analyses. The first cluster includes human, animal, and plant
      pathogens, such as Burkholderia glumae, Burkholderia pseudomallei, and
      Burkholderia mallei, as well as the 17 defined species of the Burkholderia
      cepacia complex, while the other, more recently established cluster comprises
      more than 30 non-pathogenic species, which in most cases have been found to be
      associated with plants, and thus might be considered to be potentially
      beneficial. Several species from the latter group share characteristics that are
      of use when associating with plants, such as a quorum sensing system, the
      presence of nitrogen fixation and/or nodulation genes, and the ability to degrade
      aromatic compounds. This review examines the commonalities in this growing
      subgroup of Burkholderia species and discusses their prospective biotechnological
      applications.

PMID- 21850445
TI  - Effects of stress on alcohol drinking: a review of animal studies.
AB  - RATIONALE: While stress is often proposed to play a significant role in
      influencing alcohol consumption, the relationship between stress and alcohol is
      complex and poorly understood. Over several decades, stress effects on alcohol
      drinking have been studied using a variety of animal models and experimental
      procedures, yet this large body of literature has generally produced equivocal
      results. OBJECTIVES: This paper reviews results from animal studies in which
      alcohol consumption is evaluated under conditions of acute/sub-chronic stress
      exposure or models of chronic stress exposure. Evidence also is presented
      indicating that chronic intermittent alcohol exposure serves as a stressor that
      consequently influences drinking. RESULTS: The effects of various acute/sub
      chronic stress procedures on alcohol consumption have generally been mixed, but
      most study outcomes suggest either no effect or decreased alcohol consumption. In
      contrast, most studies indicate that chronic stress, especially when administered
      early in development, results in elevated drinking later in adulthood. Chronic
      alcohol exposure constitutes a potent stressor itself, and models of chronic
      intermittent alcohol exposure reliably produce escalation of voluntary alcohol
      consumption. CONCLUSIONS: A complex and dynamic interplay among a wide array of
      genetic, biological, and environmental factors govern stress responses,
      regulation of alcohol drinking, and the circumstances in which stress modulates
      alcohol consumption. Suggestions for future directions and new approaches are
      presented that may aid in developing more sensitive and valid animal models that
      not only better mimic the clinical situation, but also provide greater
      understanding of mechanisms that underlie the complexity of stress effects on
      alcohol drinking.

PMID- 21850448
TI  - Characterisation of amyloid-induced inflammatory responses in the rat retina.
AB  - Amyloid-induced inflammation is thought to play a critical and early role in the
      pathophysiology of Alzheimer's disease. As such, robust models with relevant and
      accessible compartments that provide a means of assessing anti-inflammatory
      agents are essential for the development of therapeutic agents. In the present
      work, we have characterised the induction of inflammation in the rat retina
      following intravitreal administration of amyloid-beta protein (Abeta). Histology
      and mRNA endpoints in the retina demonstrate Abeta1-42-, but not Abeta42-1-,
      induced inflammatory responses characterised by increases in markers for
      microglia and astrocytes (ionised calcium-binding adaptor molecule 1 (iba-1),
      GFAP and nestin) and increases in mRNA for inflammatory cytokines and chemokines
      such as IL1-beta, MIP1alpha and TNFalpha. Likewise, analysis of vitreal cytokines
      also revealed increases in inflammatory cytokines and chemokines, including IL1
      beta, MIP1alpha and MCP1, induced by Abeta1-42 but not Abeta42-1. This profile of
      pro-inflammatory gene and protein expression is consistent with that observed in
      the Alzheimer's disease brain and suggest that this preclinical model may provide
      a useful relevant tool in the development of anti-inflammatory approaches
      directed towards Alzheimer's disease therapy.

PMID- 21850449
TI  - Saccadic-like visuomotor adaptation involves little if any perceptual effects.
AB  - Studies on visuomotor adaptation provide crucial clues on the functional
      properties of the human motor system. The widely studied saccadic adaptation
      paradigm is a major example of such a fruitful field of investigation. Magescas
      and Prablanc (J Cogn Neurosci 18(1):75-83, 2006) proposed a transposition of this
      protocol to arm pointing behavior, by designing an experiment in which the
      informational context of the upper limb visuomotor system is comparable to that
      of the saccadic system. Subjects were given terminal only visual feedback in a
      hand pointing task, assumed to produce a purely terminal visual error signal.
      Importantly, this paradigm has been shown to induce no saccadic adaptation.
      Although the saccadic adaptation paradigm is known to induce a predominantly
      motor adaptation with minor sensory effects, the lack of sensory changes has not
      been tested in its transposition to pointing. The present study was a partial
      replication of Magescas and Prablanc's (J Cogn Neurosci 18(1):75-83, 2006) study
      with additional control tests. A first experiment searched for a possible change
      in the static visual-to-proprioceptive congruency. A second experiment, based on
      an anti-pointing task, aimed at separating the sensory and motor effects of the
      adaptation in a dynamic condition. Consistent with most results on saccadic
      adaptation, we found a predominant adaptation of the motor components, with
      little if any involvement of the sensory components. Results are interpreted by
      proposing a causal relationship between the type of error signal and its adaptive
      effects.

PMID- 21850450
TI  - Developmental regulation of glycine receptors at efferent synapses of the murine
      cochlea.
AB  - Efferent olivocochlear feedback innervation modulates the stream of auditory
      information from cochlea to brainstem by regulating auditory nerve activity and
      controlling the contribution of cochlear outer hair cells to basilar membrane
      motion. In our previous work, we gave a first description of glycine receptors
      (GlyRs) in the rat cochlea indicating a possible localization at efferent
      cochlear synapses. Here, we analyze the developmental regulation of GlyR
      transcripts and protein within the developing murine organ of Corti (postnatal
      days P0-P21). Using quantitative RT-PCR, GlyRalpha1 and alpha2 were identified as
      the predominant GlyRalpha subunit transcripts before the onset of hearing (<P12),
      whereas GlyRalpha3 prevailed afterwards. Compared to GlyRalpha subunits, high
      levels of GlyRbeta mRNA were detected from P0-P21. Nested RT-PCR of isolated hair
      cells revealed a translocation of GlyRalpha and beta transcripts from inner to
      outer hair cells paralleling the shift of efferent cochlear innervation from
      inner to outer hair cells around the onset of hearing. This observation was
      verified on the protein level by immunostaining of GlyRalpha protein on cochlear
      cryosections. Finally, postsynaptic clusters of alpha3-containing GlyRs were
      located to efferent synapses of the medial and lateral olivocochlear bundle in
      the murine organ of Corti beyond the onset of hearing. In summary, the distinct
      developmental regulation of GlyRs in the murine cochlea advocates a contribution
      of these chloride channels to efferent olivocochlear innervation.

PMID- 21850451
TI  - An overview of the Gyrodactylus (Monogenea: Gyrodactylidae) species parasitizing
      African catfishes, and their morphological and molecular diversity.
AB  - An overview of Gyrodactylus infecting catfishes from the African continent is
      provided, including new data from Sudan, Senegal, Kenya and Mozambique. Haptoral
      sclerite morphometry and nuclear ribosomal DNA sequences revealed the presence of
      eight Gyrodactylus species. On Senegalese Synodontis nigrita, Gyrodactylus
      synodonti n. sp. and Gyrodactylus nigritae n. sp. are described. These are the
      first reports of gyrodactylid parasites from mochokid hosts. From the fins of
      North African catfish Clarias gariepinus collected in Mozambique, Gyrodactylus
      alekosi n. sp. and Gyrodactylus rysavyi were identified. G. rysavyi was also
      reported from Kenyan C. gariepinus and Senegalese Clarias anguillaris. From the
      fins of C. anguillaris studied in Senegal, two more species, Gyrodactylus
      transvaalensis and Gyrodactylus gelnari n. sp. were recognised. In addition,
      Gyrodactylus turkanaensis n. sp. from the gills of Kenyan C. gariepinus was
      described and an undescribed Gyrodactylus sp. was recorded from Sudanese
      representatives of the same host. Detailed morphometrical and molecular
      comparisons of the species are presented and discussed. The study highlights the
      hitherto understudied diversity of viviparous monogenean parasites throughout
      Africa.

PMID- 21850452
TI  - Larvicidal activity of Copaifera sp. (Leguminosae) oleoresin microcapsules
      against Aedes aegypti (Diptera: Culicidae) larvae.
AB  - Studies have demonstrated the potential of Copaifera sp. oleoresin to control
      Aedes aegypti proliferation. However, the low water solubility is a factor that
      limits its applicability. Thus, the micro- or nanoencapsulation could be an
      alternative to allow its use in larval breeding places. The purpose of this study
      was to evaluate if achievable lethal concentrations could be obtained from
      Copaifera sp. oleoresin incorporated into polymers (synthetic or natural) and,
      mainly, if it can be sustained in the residual activity compared to the pure oil
      when tested against the A. aegypti larvae. Microcapsules were prepared by the
      process of emulsification/precipitation using the polymers of cellulose acetate
      (CA) and poly(ethylene-co-methyl acrylate) (PEMA), yielding four types of
      microcapsules: MicPEMA1 and MicPEMA2, and MicCA1 and MicCA2. When using only
      Copaifera sp. oleoresin, the larvicidal activity was observed at concentrations
      of LC50 = 48 mg/L and LC99 = 149 mg/L. For MicPEMA1, the LC50 and LC99 were 78
      and 389 mg/L, respectively. Using MicPEMA2, the LC50 was 120 mg/L and LC99 > 500
      mg/L. For microcapsules MicCA1 and MicCA2, the LC50 and LC99 were 42, 164, 140,
      and 398 mg/L, respectively. For a dose of 150 mg/L of pure oleoresin, the
      residual activity remained above 20% for 10 days, while the dose of 400 mg/L
      remained above 40% for 21 days. The MicPEMA1 microcapsules showed a loss in
      residual activity up to the first day; however, it remained in activity above 40%
      for 17 days. The microcapsules of MicCA1 showed similar LC50 of pure oil with 150
      mg/L.

PMID- 21850453
TI  - Parasite communities and feeding ecology of the European sprat (Sprattus sprattus
      L.) over its range of distribution.
AB  - The metazoan parasite fauna and feeding ecology of 165 Sprattus sprattus (L.,
      1758) was studied from different geographic regions (Baltic Sea, North Sea,
      English Channel, Bay of Biscay, Mediterranean Sea). A total of 13 metazoan
      parasite species were identified including six Digenea, one Monogenea, two
      Cestoda, two Nematoda and two Crustacea. Didymozoidae indet., Lecithocladium
      excisum and Bomolochidae indet. represent new host records. The parasite species
      richness differed according to regions and ranged between 3 and 10. The most
      species-rich parasite fauna was recorded for sprats from the Bay of Biscay (North
      Atlantic), and the fishes from the Baltic Sea contained the lowest number of
      parasite species. More closely connected geographical regions, the North Sea,
      English Channel and Bay of Biscay, showed more similar parasite component
      communities compared with more distant regions. From the examined stomachs of S.
      sprattus, a total of 11 different prey items were identified, including Mollusca,
      Annelida, Crustacea and Tunicata. The highest number of prey organisms belonged
      to the crustaceans. The variety of prey items in the stomach was reflected by the
      parasite community differences and parasite species richness from the different
      regions. The feeding ecology of the fish at the sampled localities was
      responsible for the observed parasite composition and, secondarily, the
      zoogeographical distribution of the parasites, questioning the use of the
      recorded sprat parasites as biological indicators for environmental conditions
      and change.

PMID- 21850454
TI  - Detection of Leishmania donovani infection using magnetic beads-based serum
      peptide profiling by MALDI-TOF MS in mice model.
AB  - Leishmaniasis is an important parasitic disease, and definite diagnosis using a
      specific and sensitive method is the first step to cure the disease. Here, we
      present a novel diagnostic strategy based on serum peptide profiling by magnetic
      beads and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS). The serum peptides from the Leishmani donovani
      infected and healthy mice were enriched by the optimized magnetic beads. The mass
      spectrograms were acquired by MALDI-TOF MS and analyzed by the ClinProTools
      bioinformatics software from Bruker Daltonics. The diagnostic model of serum
      peptide profiling produced by the ClinProTools software could correctly detect L.
      donovani infection in mice from the third day post-infection, with the accuracy
      of 94.1%, sensitivity of 92.4%, and specificity of 97.1%, respectively. The
      results of the present study suggested that the serum peptide profiling by MALDI
      TOF MS is a novel potential tool for the clinical diagnosis of leishmaniasis.

PMID- 21850455
TI  - [Carcinoma in situ of the testis: predisposition, evolution and early detection].
AB  - Carcinoma in situ (CIS), also known as intratubular germ cell neoplasia
      unclassified, is the common obligate precursor lesion of malignant testicular
      seminomatous and non-seminomatous germ cell tumors (GCT), which show a steadily
      increasing incidence in Europe. Although GCT is a potentially curable cancer with
      excellent prognosis even in patients with organ metastasis, many patients suffer
      from chemotherapy-associated effects and some develop a secondary (non-germ cell)
      malignancy. Recently, genome-wide association studies revealed genetic
      predispositions linked to six genes (KITL, SPRY4, BAK1, TERT, ATF7IP, DMRT1).
      Exposure to environmental factors was also linked to increased prevalence of
      testicular dysgenesis and CIS/GCT by the action of hormone disruptors on
      embryonal gonadal tissue during pregnancy. By unknown mechanisms these genetic
      and environmental factors might create a disturbed microenvironment in the fetal
      testis leading to survival of embryonic germ cells and subsequent malignant
      transformation might result in CIS. Molecular pathways involved in this process
      include activated cKIT pathway and LIN28 associated deregulation of miRNA
      targets. The challenge for the future is to identify high risk patients prior to
      invasive GCT, to develop non-invasive tests for detection of CIS on seminal
      material and elucidate the precise role of the microenvironment in CIS
      initiation.

PMID- 21850456
TI  - Piecing together the puzzle of parasitic plant plastome evolution.
AB  - The importance of photosynthesis as a mode of energy production has put plastid
      genomes of plants under a constant purifying selection. This has shaped the
      characteristic features of plastid genomes across the entire spectrum of
      photosynthetic plants and has led to a highly uniform and conserved plastid
      genome with respect to structure, size, gene order, intron and editing site
      positions and coding capacity. Parasitic species that have dropped photosynthesis
      as the main energy provider share striking deviations from the plastid genome
      norm: multiple rearrangements within the circular chromosome, pseudogenization
      and gene deletions, promoter losses, intron losses as well as the extensive loss
      of mRNA editing competence have been reported. The collective loss of larger sets
      of functionally related genes like those for the plastid NADH-dehydrogenase
      complex and concomitant losses of RNA polymerase genes together with their target
      promoters point to "domino effects" where an initial loss might have triggered
      others. An example, which will be discussed in more detail, is the concomitant
      loss of the intron maturase gene matK and all introns that are supposedly subject
      to MatK-dependent splicing in two Cuscuta species.

PMID- 21850458
TI  - Co-evolution between transposable elements and their hosts: a major factor in
      genome size evolution?
AB  - Most models of genome size evolution emphasize changes in relative rates of
      and/or the efficacy of selection on insertions and deletions. However,
      transposable elements (TEs) are a major contributor to genome size evolution, and
      since they experience their own selective pressures for expansion, genome size
      changes may in part be driven by the dynamics of co-evolution between TEs and
      their hosts. Under this perspective, predictions about the conditions that allow
      for genome expansion may be altered. In this review, we outline the evidence for
      TE-host co-evolution, discuss the conditions under which these dynamics can
      change, and explore the possible contribution to the evolution of genome size.
      Aided partly by advances in our understanding of the mechanisms of TE silencing
      via small RNAs, there is growing evidence that the evolution of transposition
      rates can be important in driving genome expansion and contraction. Shifts in
      genome size and transposon abundance associated with interspecific hybridization
      and changes in mating system are consistent with an important role for
      transposition rate evolution, although other possible explanations persist. More
      understanding of the potential for the breakdown of host silencing mechanisms
      and/or the potential for TEs to evade host immune responses will improve our
      understanding of the importance of changes in TE activity in driving genome size
      evolution.

PMID- 21850459
TI  - Chromosomal evolution in Rattini (Muridae, Rodentia).
AB  - The Rattini (Muridae, Murinae) includes the biologically important model species
      Rattus norvegicus (RNO) and represents a group of rodents that are of clinical,
      agricultural and epidemiological importance. We present a comparative molecular
      cytogenetic investigation of ten Rattini species representative of the genera
      Maxomys, Leopoldamys, Niviventer, Berylmys, Bandicota and Rattus using chromosome
      banding, cross-species painting (Zoo-fluorescent in situ hybridization or FISH)
      and BAC-FISH mapping. Our results show that these taxa are characterised by slow
      to moderate rates of chromosome evolution that contrasts with the extensive
      chromosome restructuring identified in most other murid rodents, particularly the
      mouse lineage. This extends to genomic features such as NOR location (for
      example, NORs on RNO 3 are present on the corresponding chromosomes in all
      species except Bandicota savilei and Niviventer fulvescens, and the NORs on RNO
      10 are conserved in all Rattini with the exception of Rattus). The satellite I
      DNA family detected and characterised herein appears to be taxon (Rattus)
      specific, and of recent origin (consistent with a feedback model of satellite
      evolution). BAC-mapping using clones that span regions responsible for the
      morphological variability exhibited by RNO 1, 12 and 13
      (acrocentric/submetacentric) and their orthologues in Rattus species,
      demonstrated that the differences are most likely due to pericentric inversions
      as exemplified by data on Rattus tanezumi. Chromosomal characters detected using
      R. norvegicus and Maxomys surifer whole chromosome painting probes were mapped to
      a consensus sequence-based phylogenetic tree thus allowing an objective
      assessment of ancestral states for the reconstruction of the putative Rattini
      ancestral karyotype. This is thought to have comprised 46 chromosomes that, with
      the exception of a single pair of metacentric autosomes, were acrocentric in
      morphology.

PMID- 21850460
TI  - Positive findings on barium swallow in patients presenting with a "sensation of a
      lump in the throat".
AB  - Our objective is to evaluate the pickup rate of a significant pathology, on
      barium swallow, in patients who present to our clinic with a feeling of a lump in
      the throat (globus symptoms). Hospital--secondary referral centre. This is a
      retrospective study of 192 patients who had barium swallow in our department
      between August 2009 and August 2010. We revised 500 case notes to rule in 192 who
      presented with only a feeling of a lump in their throat. All patients with
      positive clinical findings, such as dysphagia, odynophagia, referred otalgia,
      hoarseness of voice, weight loss, neck swelling or vocal cord palsy, were ruled
      out. Eight patients were diagnosed on barium swallow as having significant
      pathology: five with diverticulae and three patients with oesophageal web. The
      percentage of significant pathology in our study is 4.17% (eight patients). Out
      of those eight cases, there was no malignant pathology identified on further
      panendoscopy. Our conclusion is that barium swallow adds very little to the
      diagnosis of Globus Pharyngeus, but it plays a role in the reassurance
      particularly from the patients' perspective.

PMID- 21850457
TI  - Bioinformatics and genomic analysis of transposable elements in eukaryotic
      genomes.
AB  - A major portion of most eukaryotic genomes are transposable elements (TEs).
      During evolution, TEs have introduced profound changes to genome size, structure,
      and function. As integral parts of genomes, the dynamic presence of TEs will
      continue to be a major force in reshaping genomes. Early computational analyses
      of TEs in genome sequences focused on filtering out "junk" sequences to
      facilitate gene annotation. When the high abundance and diversity of TEs in
      eukaryotic genomes were recognized, these early efforts transformed into the
      systematic genome-wide categorization and classification of TEs. The availability
      of genomic sequence data reversed the classical genetic approaches to discovering
      new TE families and superfamilies. Curated TE databases and their accurate
      annotation of genome sequences in turn facilitated the studies on TEs in a number
      of frontiers including: (1) TE-mediated changes of genome size and structure, (2)
      the influence of TEs on genome and gene functions, (3) TE regulation by host, (4)
      the evolution of TEs and their population dynamics, and (5) genomic scale studies
      of TE activity. Bioinformatics and genomic approaches have become an integral
      part of large-scale studies on TEs to extract information with pure in silico
      analyses or to assist wet lab experimental studies. The current revolution in
      genome sequencing technology facilitates further progress in the existing
      frontiers of research and emergence of new initiatives. The rapid generation of
      large-sequence datasets at record low costs on a routine basis is challenging the
      computing industry on storage capacity and manipulation speed and the
      bioinformatics community for improvement in algorithms and their implementations.

PMID- 21850461
TI  - High-fat diet-induced obesity and insulin resistance were ameliorated via
      enhanced fecal bile acid excretion in tumor necrosis factor-alpha receptor
      knockout mice.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one of the main mediators of
      inflammatory response activated by fatty acids in obesity, and this signaling
      through TNF-alpha receptor (TNFR) is responsible for obesity-associated insulin
      resistance. Recently, TNF-alpha has shown to affect lipid metabolism including
      the regulation of lipase activity and bile acid synthesis. However, there is
      scanty in vivo evidence for the involvement of TNF-alpha in this process, and the
      mechanistic role of TNFR remains unclear. In this study, TNFR2 knockout mice
      (R2KO) and wild-type (WT) mice were fed commercial normal diet (ND) or high-fat
      diet (HFD) for 8 weeks. In R2KO/HFD mice, the increase in body weight and the
      accumulation of fat were significantly ameliorated compared with WT/HFD mice in
      association with the decrease in plasma total cholesterol (137.7+/-3.1 vs. 98.6+/
      3.1 mg/dL, P<0.005), glucose (221.9+/-14.7 vs. 167.3+/-8.1 mg/dL, P<0.01), and
      insulin (5.1+/-0.3 vs. 3.4+/-0.3 ng/mL, P<0.05). Fecal excretion of lipid
      contents was significantly increased in R2KO mice. In R2KO/HFD mice, the decrease
      in hepatic cholesterol-7a-hydroxylase activity, the rate-limiting enzyme in bile
      acid synthesis, was inhibited (1.7+/-0.2 vs. 8.1+/-1.0 pmol/min/mg protein,
      P<0.01). These results suggested that HFD-induced obesity with metabolic
      derangements could be ameliorated in mice lacking TNF-alpha receptor 2 via
      increasing fecal bile acid and lipid content excretion. Therefore, TNF-alpha
      signaling through TNFR2 is essentially involved in the bile acid synthesis and
      excretion of lipids, resulting in its beneficial effects.

PMID- 21850462
TI  - Early detection and intervention in bipolar affective disorder: targeting the
      development of the disorder.
AB  - The diagnosis of bipolar affective disorder (BD) is often delayed, and preceded
      by incorrect diagnoses and potentially harmful treatment, while the development
      of the disorder is associated with suicidal behavior and help seeking. Several
      clinical features have been linked to an increased risk of going on to develop
      BD, in particular attenuated symptoms of BD, personality traits such as
      cyclothymia, and general psychopathologic symptoms. Several of these show high
      specificity, indicating that it may be possible to target detection and
      intervention in individuals at high risk of BD and perhaps moderate the course of
      the illness and improve treatment outcome. This article summarizes recent
      evidence on the characteristics of the prodrome to BD and discusses the potential
      value and challenges of early detection and intervention in BD.

PMID- 21850463
TI  - UBC and YWHAZ as suitable reference genes for accurate normalisation of gene
      expression using MCF7, HCT116 and HepG2 cell lines.
AB  - Relative quantification of in vitro gene expression using real-time PCR requires
      stably expressed reference gene for normalisation. In this study, total RNA from
      MCF7, HCT116 and HepG2 cells were extracted and converted to cDNA using
      commercially available kit, and real-time PCR was then performed to analyse the
      expression levels of twelve reference genes to select the most ideal reference
      gene for accurate normalisation in gene expression study. geNorm and NormFinder
      software were used to analyse the stabilities of the reference genes, which
      showed a wide range of C(t) values. The geNorm analysis showed the following
      ranking for stability of genes: UBC, YWHAZ > RPLP > TBP > ACTB > HPRT1 > PPIA >
      GAPDH > GUSB > B2M > TUBB > RRN18S. A similar ranking of reference genes was
      obtained by NormFinder, and the four most stable reference genes were identical
      using both approaches. UBC and YWHAZ were proposed to be the two most suitable
      reference genes based on the above analyses. To further assess the stabilities of
      the UBC and YWHAZ in a formal experiment, MCF7, HCT116 and HepG2 cell lines were
      subjected to treatments with 5-aza-dC and TSA. Both UBC and YWHAZ exhibited
      stable expression levels across control and treatment groups. Therefore, we
      propose that UBC and YWHAZ are the two most suitable reference genes for our gene
      expression studies using MCF7, HCT116 and HepG2 cell lines.

PMID- 21850464
TI  - A phase I study of bortezomib and temozolomide in patients with advanced solid
      tumors.
AB  - PURPOSE: The primary objective was to determine the maximum tolerated doses
      (MTDs) of the combination of bortezomib and temozolomide in patients with solid
      tumors. The secondary objective was to evaluate the pharmacokinetics (PK) of
      bortezomib with and without concurrent hepatic enzyme-inducing anticonvulsants
      (HEIAs). METHODS: Bortezomib was administered on days 2, 5, 9, and 12;
      temozolomide on days 1-5 of a 28-day cycle. Dose escalation proceeded using a
      standard 3+3 design. Patients with primary or metastatic brain tumors were
      eligible and were stratified based on whether they were taking HEIAs or not.
      RESULTS: Of the 25 patients enrolled, 22 were not taking HEIAs. MTDs were only
      given to patients not receiving HEIAs. Dose-limiting toxicities (DLTs) consisted
      of grade-3 constipation, hyponatremia, fatigue, elevated hepatic enzymes, and
      grade-4 neutropenia, thrombocytopenia, constipation, and abdominal pain. Stable
      disease (>8 weeks) was observed in 5 patients. Bortezomib systemic clearance
      (CL(sys)) on day 9 was 51% of the CL(sys) on day 2 (P < 0.01) Similarly, the
      normalized area under the concentration-time curve (norm AUC) on day 9 was 1.9
      times the norm AUC on day 2 (P < 0.01). The median bortezomib CL(sys) on days 2
      and 9 was significantly higher (P < 0.04) in patients taking HEIAs, and the
      median norm AUC was correspondingly lower (P < 0.04). CONCLUSIONS: The MTDs for
      the combination of bortezomib and temozolomide in patients not taking HEIAs are
      1.3 and 200 mg/m(2), respectively. The rate of bortezomib elimination in patients
      taking HEIAs was increased twofold. Additional trials are needed to better define
      the optimal dosing in such patients.

PMID- 21850465
TI  - Pharmacokinetics of trabectedin on hemodialysis: an application for the
      management of cancer patients with end-stage renal disease.
AB  - PURPOSE: The pharmacokinetics of trabectedin has never been reported in patients
      with impaired renal function or in patients on hemodialysis. METHODS: We examined
      trabectedin PK in a patient on hemodialysis, starting trabectedin therapy at a
      standard dose for recurrence of a retroperitoneal myxoid liposarcoma that had
      occurred under immunosuppressive drugs for kidney transplant. RESULTS: As
      compared with a population with normal renal function, the study patient
      presented a higher C (max) and AUC, with lower clearance, terminal half-life, and
      volume of distribution. The low dialysis clearance, accounting for a minor part
      of the total body clearance and the absence of detectable trabectedin in the
      dialysate samples, suggests that hemodialysis does not efficiently clear
      trabectedin. Trabectedin tolerance was good. CONCLUSIONS: This case reports for
      the first time the feasibility of trabectedin therapy in a hemodialyzed patient.
      Given the rising incidence of cancer in patients with end-stage renal disease, it
      is crucial to provide data that improve the management of anticancer drugs in
      dialyzed patients.

PMID- 21850466
TI  - The use of GTX as second-line and later chemotherapy for metastatic pancreatic
      cancer: a retrospective analysis.
AB  - PURPOSE: There are limited data regarding the role of second-line treatment for
      metastatic pancreatic cancer (mPC) after the failure of initial chemotherapy. No
      data exist on the use of GTX after the failure of first-line therapy. PATIENTS
      AND METHODS: We identified patients who were given GTX chemotherapy for a
      diagnosis of mPC after the failure of initial therapy. Demographic features,
      progression-free (PFS) and overall survival (OS), response to treatment, and
      toxicities were recorded. RESULTS: The 59 evaluable patients received a median of
      2 prior therapies. Three had no prior gemcitabine. Median PS was 1. Median
      survival was 22 weeks; progression-free survival was 9.9 weeks. Survival did not
      correlate with the number of prior regimens but trended with PS. There were no
      radiologic responses; those with stable disease (n = 21) had a better survival
      than those with progression (n = 29) or unevaluable patients (n = 9). Median
      survival was 38.3, 15.0, and 7.4 weeks, respectively. Grade 3 and 4 toxicities
      included leucopenia (n = 14), anemia (n = 7), and thrombocytopenia (n = 6).
      Hospitalizations were required in 21 patients, for febrile neutropenia (n = 7),
      non-neutropenic infection (n = 3), pulmonary embolus (n = 2), anemia or failure
      to thrive (n = 9). A 75% drop or more in CA 19-9 correlated with improved
      survival. CONCLUSIONS: GTX is an active regimen in patients previously treated
      with gemcitabine for mPC. Better performance status and >75% drop in pretreatment
      CA 19-9 were associated with longer survival. The number of prior regimens did
      not predict for survival duration.

PMID- 21850467
TI  - Parker's sneak-guard model revisited: why do reproductively parasitic males
      heavily invest in testes?
AB  - Alternative reproductive tactics are widespread in males and may cause
      intraspecific differences in testes investment. Parker's sneak-guard model
      predicts that sneaker males, who mate under sperm competition risk, invest in
      testes relatively more than bourgeois conspecifics that have lower risk. Given
      that sneakers are much smaller than bourgeois males, sneakers may increase testes
      investment to overcome their limited sperm productivity because of their small
      body sizes. In this study, we examined the mechanism that mediates differential
      testes investment across tactics in the Lake Tanganyika cichlid fish Lamprologus
      callipterus. In the Rumonge population of Burundi, bourgeois males are small
      compared with those in other populations and have a body size close to sneaky
      dwarf males. Therefore, if differences in relative testis investment depend on
      sperm competition, the rank order of relative testis investment should be dwarf
      males > bourgeois males in Rumonge = bourgeois males in the other populations. If
      differences in relative testis investment depend on body size, the rank order of
      relative testes investment should be dwarf males > bourgeois males in Rumonge >
      bourgeois males in the other populations. Comparisons of relative testis
      investment among the three male groups supported the role of sperm competition,
      as predicted by the sneak-guard model. Nevertheless, the effects of absolute body
      size on testes investment should be considered to understand the mechanisms
      underlying intraspecific variation in testes investment caused by alternative
      reproductive tactics.

PMID- 21850468
TI  - Actual state of EndActive ventricular endoscopy.
AB  - PURPOSE: We assessed usability and applicability of a rigid, multidirectional
      steerable videoendoscope (EndActive, Karl Storz GmbH, Tuttlingen, Germany) for
      endoscopic third ventriculostomy and compared our experience with reports about
      other multidirectional endoscopes. METHODS: The prototype is a 4-mm-diameter
      rigid videoendoscope with an integrated image sensor comprising an embedded light
      source, offering a free viewing direction in a range of 160 degrees  while the
      tip itself does not move. In five specimens (ten sides), we introduced the
      endoscope via precoronal burr holes through the lateral ventricle and foramen of
      Monro into the third ventricle. The endoscope's tip was positioned at the level
      of the mamillary bodies and the previously defined anatomical target structures;
      anteriorly, the optic chiasm, anterior commissure, infundibulum, tuber cinereum
      and posteriorly, the entrance to the mesencephalic aqueduct and posterior
      commissure were inspected. RESULTS: A single insertion of the videoendoscope was
      sufficient to explore with the multiplanar viewing mechanism the entire third
      ventricle. The prototype videoendoscope may be held like a microsurgical
      instrument in one hand. It is feasible to control movements precisely due to the
      reduced weight and ergonomic shape of the device. CONCLUSIONS: The prototype
      EndActive has the potential to fit in the current concept of ETV and enrich the
      setting adding working economy and viewing variability.

PMID- 21850469
TI  - Widespread expressions of immunoglobulin superfamily proteins in cancer cells.
AB  - RP215 monoclonal antibody (Mab) was shown to recognize a carbohydrate-associated
      epitope of cancer cell-expressed glycoproteins, known as CA215. Extensive MALDI
      TOF MS analysis was performed to search for the molecular identity of CA215.
      Besides immunoglobulin (Ig) heavy chains, homology to human T-cell receptors
      (TCR) and Ig-like cell adhesion molecules was also detected. By using RT-PCR and
      cDNA sequencing, it was observed that as many as 80% of cancer cell lines showed
      significant levels of gene expressions of TCR-alpha and TCR-beta. Selected Ig
      like cell adhesion molecules such as CD47, CD54, CD58 and CD 147 were also highly
      expressed among all the cell lines tested. In contrast, co-receptors and co
      stimulators of TCR such as CD3, CD4 and CD8 were rarely expressed demonstrating
      the non-functional nature of TCR in cancer cells. Results of immunohistochemical
      staining and Western blot assays of cancer cell lines as well as cancerous tissue
      sections were consistent with these observations. Anti-TCR and anti-human IgG
      antibodies were shown to induce complement-dependent cytotoxicity and apoptosis
      of cultured cancer cells indicating the surface nature of Ig-like proteins. Based
      on these experimental observations, it was hypothesized that the expressions of
      these immunoglobulin superfamily (IgSF) proteins may be relevant to the immune
      protection and proliferations of cancer cells during carcinogenesis or cancer
      progression. Surface-bound TCR-like proteins as well as immunoglobulins may be
      the potential targets for RP215-based anti-cancer drugs.

PMID- 21850470
TI  - Design of a novel mobility device controlled by the feet motion of a standing
      child: a feasibility study.
AB  - Self-generated mobility is a major contributor to the physical, emotional,
      cognitive, and social development of infants and toddlers. When young children
      have disorders that hinder self locomotion, their development is at risk for
      delay. Independent mobility via traditional power mobility devices may prevent
      this delay, but do little to encourage the child's development of gross motor
      skills. This research aims to develop a bio-driven mobile-assistive device that
      is controlled and driven by moving the feet, which may encourage the development
      of gross motor skills. In this study, system feasibility is shown by experiments
      on five typically developing toddlers and one special needs toddler with spastic
      cerebral palsy. Children were placed in the bio-driven device and instructed to
      navigate through a maze. All subjects were able to successfully complete the maze
      in multiple trials. In addition, two toddlers showed evidence of improved driving
      skill by completing the maze in shorter times in successive trials on a given
      testing day. The results suggest that such a device is feasible for purposeful
      driving. Recommendations are given for the device and protocol redesign for
      related future testing.

PMID- 21850471
TI  - Guidelines for imaging retinoblastoma: imaging principles and MRI
      standardization.
AB  - Retinoblastoma is the most common intraocular tumor in children. The diagnosis is
      usually established by the ophthalmologist on the basis of fundoscopy and US.
      Together with US, high-resolution MRI has emerged as an important imaging
      modality for pretreatment assessment, i.e. for diagnostic confirmation, detection
      of local tumor extent, detection of associated developmental malformation of the
      brain and detection of associated intracranial primitive neuroectodermal tumor
      (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic
      evaluation of retinoblastoma or mimicking lesions are presented, based on
      consensus among members of the European Retinoblastoma Imaging Collaboration
      (ERIC). The most appropriate techniques for imaging in a child with leukocoria
      are reviewed. CT is no longer recommended. Implementation of a standardized MRI
      protocol for retinoblastoma in clinical practice may benefit children worldwide,
      especially those with hereditary retinoblastoma, since a decreased use of CT
      reduces the exposure to ionizing radiation.

PMID- 21850472
TI  - The use of psychotherapeutic interventions by primary care GPs in Ireland in the
      treatment of their methadone patients: a grounded theory study.
AB  - BACKGROUND: The methadone protocol placed responsibility on general practitioners
      (GPs) for the methadone treatment of stabilised drug-addicted patients. The
      protocol emphasised a medico-pharmacological model with minor reference to
      psychotherapeutic treatment. AIM: This qualitative study investigated how primary
      care GPs in Ireland use psychotherapeutic interventions in the treatment of
      methadone patients. METHOD: A grounded theory methodology was used. FINDINGS:
      There is a wide variation in the beliefs and knowledge of methadone-prescribing
      GPs regarding the efficacy of psychotherapeutic interventions for patients on
      methadone maintenance. GPs do not formally integrate psychotherapeutic
      interventions into methadone patient treatment. Accessing psychotherapeutic
      services raises concerns for GPs in terms of availability, location and quality.
      Primary care GPs who offer methadone maintenance view opiate abuse as a health
      issue similar to other such issues within their community. They take a holistic
      view of their methadone patient and, without formal guidelines, develop
      individual approaches to the use of psychotherapeutic interventions. The absence
      of a framework for the use of psychotherapeutic interventions in primary care
      methadone treatment in Ireland militates against the development of a basis for
      improving practice.

PMID- 21850473
TI  - Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic
      acid down-regulate MMPs in rheumatoid arthritis.
AB  - 10-hydroxy-2-decenoic acid (10H2DA) is suggested to be a potential medication for
      rheumatoid arthritis (RA) by activation of matrix metalloproteinases (MMPs) via
      mitogen-activated protein kinase signaling pathways. The aim of the present work
      was to seek differentially expressed proteins in rheumatoid arthritis synovial
      fibroblasts (RASFs) treated with 10H2DA by comparative proteomics analysis. Two
      dimensional electrophoresis (2-DE) and LC-MS/MS were performed to identify
      changes in protein expression after 24-h 10H2DA treatment. Differentially
      expressed proteins were identified by real-time PCR and Western blot analysis.
      Influence of down-regulation of connective tissue growth factor (CTGF) expression
      on MMPs was studied by RNAi. Ten proteins were up-regulated and 9 proteins were
      down-regulated after 24-h 10H2DA treatment. A total of 19 differentially
      expressed proteins were identified and found to be associated with glycolysis,
      lipid metabolism, cell adhesion, ATP synthesis, oxidation reduction, and anti
      apoptosis. CTGF, a member of the C-terminal cystein-rich proteins (CCN) family,
      was down-regulated after 24-h 10H2DA treatment. MMPs were down-regulated after
      RNAi (CTGFi). These results suggest that CTGF is a regulator factor in the
      expression of MMPs, and 10H2DA down-regulate the concentration of MMPs probably
      by down-regulating the expression of CTGF.

PMID- 21850474
TI  - The distribution and frequency of oral veillonella spp. in the tongue biofilm of
      healthy young adults.
AB  - Five species of oral Veillonella, V. atypica, V. denticariosi, V. dispar, V.
      parvula, and V. rogosae, have been suggested to be early colonizers of dental
      biofilm and causes of opportunistic infections and oral malodor. However, the
      pathogenicity and the distribution of oral Veillonella spp. have not been
      clarified. Previously, oral Veillonella spp. were identified by using 16S rDNA
      sequence analysis. In addition, recently, Veillonella isolates from human tongue
      biofilm were identified by rpoB gene sequences, but these procedures are time
      consuming and complex. To overcome this problem, Igarashi et al. have designed
      species-specific primer sets for oral Veillonella spp. by using a highly variable
      region in the rpoB gene. In the present study, the distribution and frequency of
      oral Veillonella spp. in the tongue biofilm of healthy adults in their 20s were
      examined by using these species-specific primer sets. Tongue biofilms of these
      subjects were found to be divided into two groups based on the distribution and
      frequency of oral Veillonella spp. In one group, V. rogosae was the predominant
      species; the other group consisted of mainly V. dispar and V. atypica. Multiple
      factors may influence these differences in distribution and frequency of oral
      Veillonella spp. in tongue biofilm. This is the first report also demonstrating
      the availability of the species-specific primer sets for PCR to determine the
      distribution and frequency of oral Veillonella spp. in the tongue biofilm of
      healthy adults in their 20s.

PMID- 21850475
TI  - Identification of yeast associated with the planthopper, Perkinsiella
      saccharicida: potential applications for Fiji leaf gall control.
AB  - Yeasts associate with numerous insects, and they can assist the metabolic
      processes within their hosts. Two distinct yeasts were identified by PCR within
      the planthopper Perkinsiella saccharicida, the vector of Fiji disease virus to
      sugarcane. The utility of both microbes for potential paratransgenic approaches
      to control Fiji leaf gall (FLG) was assessed. Phylogenetic analysis showed one of
      the microbes is related to yeast-like symbionts from the planthoppers: Laodelphax
      striatellus, Nilaparvata lugens, and Sogetella furcifera. The second yeast was a
      member of the Candida genus, a group that has been identified in beetles and
      recently described in planthoppers. Microscopy revealed the presence of yeast in
      the fat body of P. saccharicida. The Candida yeast was cultured, and
      transformation was accomplished by electroporation of Candida albicans codon
      optimized plasmids, designed to integrate into the genome via homologous
      recombination. Transgenic lines conferred resistance to the antibiotic
      nourseothricin and expression of green fluorescent protein was observed in a
      proportion of the yeast cells. Stably transformed yeast lines could not be
      isolated as the integrative plasmids presumably replicated within the yeast
      without integration into the genome. If stable transformation can be achieved,
      then this yeast may be useful as an agent for a paratransgenic control of FLG.

PMID- 21850476
TI  - Micropropagation of a Thai medicinal plant for women's health, Curcuma comosa
      Roxb., via shoot and microrhizome inductions.
AB  - We studied the effects of explant types, plant growth regulators, and sucrose
      concentrations on shoot and microrhizome inductions of Curcuma comosa Roxb., an
      important Thai medicinal plant for women's health. Explant types significantly
      affected shoot induction of the plant. The maximum shoot multiplication rate of
      11.82 +/- 1.03 shoots/responding explant was obtained when culturing terminal bud
      explants on semi-solid Murashige and Skoog (MS) medium supplemented with 18.16
      MUM thidiazuron for 8 weeks. Subsequently, they were transferred to a semi-solid
      MS medium without plant growth regulators for 4 weeks. The regenerated shoots
      produced roots spontaneously. Rooted plantlets were successfully transferred to
      the soil. Microrhizome induction was significantly influenced by sucrose
      concentrations, but not by 6-benzyladenine (BA). Liquid MS medium with a
      combination of 17.76 MUM BA and 50 g L(-1) sucrose was optimal for microrhizome
      induction of C. comosa. After 12 weeks of culture, the microrhizome induction
      rate was 3.36 +/- 0.44 microrhizomes/responding explant. Starch accumulation in
      microrhizomes increased with higher sugar concentration and with longer duration
      of culture. The microrhizomes were allowed to germinate under greenhouse
      conditions and further developed into normal plants. The protocols established
      will be used for the production of uniform plantlets suitable for field
      plantation for the herbal industry.

PMID- 21850477
TI  - Pea powdery mildew er1 resistance is associated to loss-of-function mutations at
      a MLO homologous locus.
AB  - The powdery mildew disease affects several crop species and is also one of the
      major threats for pea (Pisum sativum L.) cultivation all over the world. The
      recessive gene er1, first described over 60 years ago, is well known in pea
      breeding, as it still maintains its efficiency as a powdery mildew resistance
      source. Genetic and phytopathological features of er1 resistance are similar to
      those of barley, Arabidopsis, and tomato mlo powdery mildew resistance, which is
      caused by the loss of function of specific members of the MLO gene family. Here,
      we describe the obtainment of a novel er1 resistant line by experimental
      mutagenesis with the alkylating agent diethyl sulfate. This line was found to
      carry a single nucleotide polymorphism in the PsMLO1 gene sequence, predicted to
      result in premature termination of translation and a non-functional protein. A
      cleaved amplified polymorphic sequence (CAPS) marker was developed on the
      mutation site and shown to be fully co-segregating with resistance in F(2)
      individuals. Sequencing of PsMLO1 from three powdery mildew resistant cultivars
      also revealed the presence of loss-of-function mutations. Taken together, results
      reported in this study strongly indicate the identity between er1 and mlo
      resistances and are expected to be of great breeding importance for the
      development of resistant cultivars via marker-assisted selection.

PMID- 21850478
TI  - Major locus and other novel additive and epistatic loci involved in modulation of
      isoflavone concentration in soybean seeds.
AB  - Seeds of soybean [Glycine max (L.) Merr.] accumulate more isoflavones than any
      tissue of any plant species. In other plant parts, isoflavones are usually
      released to counteract the effects of various biotic and abiotic stresses.
      Because of the benefits to the plant and positive implications that consumption
      may have on human health, increasing isoflavones is a goal of many soybean
      breeding programs. However, altering isoflavone levels through marker-assisted
      selection (MAS) has been impractical due to the small and often environmentally
      variable contributions that each individual quantitative trait locus (QTL) has on
      total isoflavones. In this study, we developed a Magellan * PI 437654 F(7)-RIL
      population to construct a highly saturated non-redundant linkage map that
      encompassed 451 SNP and SSR molecular markers and used it to locate genomic
      regions that govern accumulation of isoflavones in the seeds of soybean. Five
      QTLs were found that contribute to the concentration of isoflavones, having
      single or multiple additive effects on isoflavone component traits. We also
      validated a major locus which alone accounted for up to 10% of the phenotypic
      variance for glycitein, and 35-37% for genistein, daidzein and the sum of all
      three soybean isoflavones. This QTL was consistently associated with increased
      concentration of isoflavones across different locations, years and crosses. It
      was the most important QTL in terms of net increased amounts of all isoflavone
      forms. Our results suggest that this locus would be an excellent candidate to
      target for MAS. Also, several minor QTLs were identified that interacted in an
      additive-by-additive epistatic manner, to increase isoflavone concentration.

PMID- 21850479
TI  - Molecular evolution of the clustered MIC-3 multigene family of Gossypium species.
AB  - The Gossypium MIC-3 (Meloidogyne Induced Cotton-3) gene family is of great
      interest for molecular evolutionary studies because of its uniqueness to
      Gossypium species, multi-gene content, clustered localization, and root-knot
      nematode resistance-associated features. Molecular evolution of the MIC-3 gene
      family was studied in 15 tetraploid and diploid Gossypium genotypes that
      collectively represent seven phylogenetically distinct genomes. Synonymous (d(S))
      and non-synonymous (d(N)) nucleotide substitution rates suggest that the second
      of the two exons of the MIC-3 genes has been under strong positive selection
      pressure, while the first exon has been under strong purifying selection to
      preserve function. Based on nucleotide substitution rates, we conclude that MIC-3
      genes are evolving by a birth-and-death process and that a 'gene amplification'
      mechanism has helped to retain all duplicate copies, which best fits with the
      "bait and switch" model of R-gene evolution. The data indicate MIC-3 gene
      duplication events occurred at various rates, once per 1 million years (MY) in
      the allotetraploids, once per ~2 MY in the A/F genome clade, and once per ~8 MY
      in the D-genome clade. Variations in the MIC-3 gene family seem to reflect
      evolutionary selection for increased functional stability, while also expanding
      the capacity to develop novel "switch" pockets for responding to diverse pests
      and pathogens. Such evolutionary roles are congruent with the hypothesis that
      members of this unique resistance gene family provide fitness advantages in
      Gossypium.

PMID- 21850480
TI  - Quantitative analysis of optical coherence tomography and histopathology images
      of normal and dysplastic oral mucosal tissues.
AB  - Selecting the most representative site for biopsy is crucial in establishing a
      definitive diagnosis of oral epithelial dysplasia. The current process involves
      clinical examination that can be subjective and prone to sampling errors. The aim
      of this study was therefore to investigate the use of optical coherence
      tomography (OCT) for differentiation of normal and dysplastic oral epithelial
      samples, with a view to developing an objective and reproducible approach for
      biopsy site selection. Biopsy samples from patients with fibro-epithelial polyps
      (n = 13), mild dysplasia (n = 2), and moderate/severe dysplasia (n = 4) were
      scanned at 5-MUm intervals using an OCT microscope and subsequently processed and
      stained with hematoxylin and eosin (H&E). Epithelial differentiation was measured
      from the rate of change (gradient) of the backscattered light intensity in the
      OCT signal as a function of depth. This parameter is directly related to the
      density of optical scattering from the cell nuclei. OCT images of normal oral
      epithelium showed a clear delineation of the mucosal layers observed in the
      matching histology. However, OCT images of oral dysplasia did not clearly
      identify the individual mucosal layers because of the increased density of
      abnormal cell nuclei, which impeded light penetration. Quantitative analysis on
      2D-OCT and histology images differentiated dysplasia from normal control samples.
      Similar analysis on 3D-OCT datasets resulted in the reclassification of biopsy
      samples into the normal/mild and moderate/severe groups. Quantitative
      differentiation of normal and dysplastic lesions using OCT offers a non-invasive
      objective approach for localizing the most representative site to biopsy,
      particularly in oral lesions with similar clinical features.

PMID- 21850481
TI  - Tetralogy of Fallot with inverted great arteries {S, D, I}: case report,
      literature review, and discussion of embryology.

PMID- 21850482
TI  - Postoperative outcome for hyperglycemic pediatric cardiac surgery patients.
AB  - This prospective cohort study aimed to determine the morbidity and mortality
      among hyperglycemic pediatric patients after cardiac surgery. The study was
      conducted in a pediatric intensive care unit (PICU) for cardiac surgery patients
      at a university-affiliated, referral, heart hospital. A total of 379 postcardiac
      surgery pediatric patients participated in the study. No interventions were
      performed. Measurements of blood glucose level together with other clinical and
      laboratory data were collected on postoperative days 1, 2, 3, and 7. Mean blood
      glucose level exceeding 126 mg/dl was considered hyperglycemia, and a level
      exceeding 200 mg/dl determined severe hyperglycemia. These measurements were
      analyzed for association with major complications and death. Hyperglycemia was
      common (86%) in this cohort study. There was no statistical correlation between
      hyperglycemia and death or major complications, but patients with severe
      hyperglycemia showed a significantly higher mortality rate (16/64 deaths [25%]
      vs. 13/315 deaths [4.12%]; P < 0.001]) and more morbidities (16/64 [25%] vs.
      43/315 [13.65%]; P = 0.022). Severe hyperglycemia was independently associated
      with mortality according to multivariate logistic regression. Hyperglycemia is
      quite prevalent among pediatric patients after cardiac surgeries. Severe
      hyperglycemia is associated with higher morbidity and mortality rates in this
      patient population.

PMID- 21850483
TI  - Dual microfluidic perifusion networks for concurrent islet perifusion and optical
      imaging.
AB  - This study explores a new class of duplex microfluidic device which utilizes a
      dual perifusion network to simultaneously perform live-cell optical imaging of
      physiological activities and study insulin release kinetics on two islet
      populations. This device also incorporates on-chip staggered herringbone mixers
      (SHMs) to increase mixing efficiency and facilitate the generation of user
      defined chemical gradients. Mouse islets are used to simultaneously measure
      dynamic insulin release, changes in mitochondrial potentials, and calcium influx
      in response to insulin secretagogues (glucose and tolbutamide), and show a high
      signal-to-noise ratio and spatiotemporal resolution of all measured parameters
      for both perifusion chambers. This system has many potential applications for
      studying beta-cell physiology and pathophysiology, as well as for therapeutic
      drug screening. This dual perifusion device is not limited to islet studies and
      could easily be applied to other tissues and cells without major modifications.

PMID- 21850484
TI  - Application of nanoscale zero valent iron (NZVI) for groundwater remediation in
      Europe.
AB  - PURPOSE: Nanoscale zero valent iron (NZVI) is emerging as a new option for the
      treatment of contaminated soil and groundwater targeting mainly chlorinated
      organic contaminants (e.g., solvents, pesticides) and inorganic anions or metals.
      The purpose of this article is to give a short overview of the practical
      experience with NZVI applications in Europe and to present a comparison to the
      situation in the USA. Furthermore, the reasons for the difference in technology
      use are discussed. METHOD: The results in this article are based on an extensive
      literature review and structured discussions in an expert workshop with experts
      from Europe and the USA. The evaluation of the experiences was based on a SWOT
      (strength, weakness, opportunity, threat) analysis. RESULT: There are significant
      differences in the extent and type of technology used between NZVI applications
      in Europe and the USA. In Europe, only three full-scale remediations with NZVI
      have been carried out so far, while NZVI is an established treatment method in
      the USA. Bimetallic particles and emulsified NZVI, which are extensively used in
      the USA, have not yet been applied in Europe. Economic constraints and the
      precautionary attitude in Europe raise questions regarding whether NZVI is a cost
      effective method for aquifer remediation. Challenges to the commercialization of
      NZVI include mainly non-technical aspects such as the possibility of a public
      backlash, the fact that the technology is largely unknown to consultants,
      governments and site owners as well as the lack of long-term experiences.
      CONCLUSION: Despite these concerns, the results of the current field applications
      with respect to contaminant reduction are promising, and no major adverse impacts
      on the environment have been reported so far. It is thus expected that these
      trials will contribute to promoting the technology in Europe.

PMID- 21850485
TI  - How readers spontaneously interpret man-suffix words: evidence from eye
      movements.
AB  - This study investigated whether readers are more likely to assign a male referent
      to man-suffix terms (e.g. chairman) than to gender-neutral alternatives (e.g.,
      chairperson) during reading, and whether this bias differs as a function of age.
      Younger and older adults' eye movements were monitored while reading passages
      containing phrases such as "The chairman/chairperson familiarized herself
      with..." On-line eye fixation data provided strong evidence that man-suffix words
      were more likely to evoke the expectation of a male referent in both age groups.
      Younger readers demonstrated inflated processing times when first encountering
      herself after chairman relative to chairperson, and they tended to make more
      regressive fixations to chairman. Older readers did not show the effect when
      initially encountering herself, but they spent disproportionately longer looking
      back to chairman and herself. The study provides empirical support for copy
      editing policies that mandate the use of explicitly gender-neutral suffix terms
      in place of man-suffix terms.

PMID- 21850486
TI  - The natural diterpene ent-16beta-17alpha-dihydroxykaurane down-regulates Bcl-2 by
      disruption of the Ap-2alpha/Rb transcription activating complex and induces E2F1
      up-regulation in MCF-7 cells.
AB  - ent-Kauranes are diterpene-type compounds commonly found in most plant species,
      especially from the Euphorbiaceae family. These compounds have been studied due
      to their anti-inflammatory and anti-tumor properties. Regulation of apoptosis, or
      programmed cell death, is commonly bypassed by tumoral cells, giving rise to
      uncontrolled proliferating cells, which eventually become carcinogenic. In a
      previous work, we showed that both mRNA and protein expression levels of the
      antiapoptotic gene Bcl-2 are reduced in MCF-7 cancer cells by the effect of the
      natural diterpene ent-16beta-17alpha-dihydroxykaurane (DHK). This effect was not
      directly associated with the inactivation of NF-kappaB, as has been shown with
      other diterpenes compounds. Herein, we report that DHK is dissociating the
      Ap2alpha-Rb activating complex, affecting its binding ability for the Bcl-2 gene
      promoter. These events down-regulate Bcl-2 and is temporally accompanied by the
      induction of E2F1 and its target pro-apoptotic gene Puma. Disruption of the Rb
      Ap2alpha activation complex was corroborated by chromatin immunoprecipitation and
      protein immunolocalization, which also revealed that Ap2alpha sorts out from the
      nucleus and relocalizes in the cell periphery. Taken together, our study confirms
      the regulation of Bcl-2 gene transcription by the Ap2alpha-Rb complex and
      describes a singular protein relocalization for Ap2alpha induced by DHK,
      implicating a new potential therapeutic target to differentially onset apoptosis
      in tumor cells.

PMID- 21850487
TI  - Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating
      expression of transcription factor Nrf2 and HO-1 in rats.
AB  - Oxidative stress damage plays a vital role in cerebral ischemia/reperfusion (I/R)
      pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant
      response element (ARE) signaling pathway can be activated by pharmacological and
      dietary means to attenuate cellular oxidative stress. Resveratrol, a plant
      derived polyphenolic compound, has antioxidant property. Recent studies have
      demonstrated that resveratrol has protective effects against cerebral I/R injury.
      However, little is known about its mechanism. Hence, this study identified the
      neuroprotective effect of resveratrol pretreatment and elucidate the Nrf2/ARE
      signaling mechanism after focal cerebral I/R injury in rats. Adult male Sprague
      Dawley rats were randomly assigned to sham-operated group, ischemia/reperfusion
      physiological saline-treated group, and ischemia/reperfusion resveratrol
      pretreatmented (15 and 30 mg/kg) groups. Rats were pretreatmented with
      resveratrol or physiological saline of corresponding volume administered
      intraperitoneally for 7 days before surgery and 30 min before middle cerebral
      artery occlusion. At 24 h after reperfusion, neurological score, infarct volume,
      and brain water content were assessed. Oxidative stress was evaluated by
      malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity.
      Pathological changes of brain tissue were observed by HE staining. RT-PCR and
      Western blot analysed the expression of nuclear factor erythroid 2-related factor
      2 (Nrf2) and heme oxygenase-1 (HO-1). TUNEL staining detected apoptotic cells.
      The protein expression of Caspase-3 were studied by immunohistochemistry.
      Resveratrol pretreatment significantly ameliorated neurological scores, reduced
      infarct volume and brain water content, decreased MDA levels, restored the SOD
      activity, upregulated the protein and mRNA expression of Nrf2 and HO-1,
      downregulated the protein expression of caspase-3. TUNEL-positive cells
      significantly decreased compared with the physiological saline-treated group. HE
      staining also showed that resveratrol significantly improved neuronal injury.
      These results showed that resveratrol pretreatment had neuroprotective effects on
      cerebral I/R injury. This neuroprotective effect is likely exerted by upregulated
      expression of transcription factor Nrf2 and HO-1 to ameliorate oxidative damage,
      decreased the protein expression of caspase-3. Our finding is important for
      understanding the neuroprotective mechanism of resveratrol and promoting its
      clinical therapeutic utility.

PMID- 21850488
TI  - Philani Plus (+): a Mentor Mother community health worker home visiting program
      to improve maternal and infants' outcomes.
AB  - Pregnant mothers in South African townships face multiple health risks for
      themselves and their babies. Existing clinic-based services face barriers to
      access, utilization, and human resource capacities. Home visiting by community
      health workers (CHW) can mitigate such barriers. The Philani Plus (+)
      Intervention Program builds upon the original Philani CHW home-visiting
      intervention program for maternal and child nutrition by integrating content and
      activities to address HIV, alcohol, and mental health. Pregnant Mothers at Risk
      (MAR) for HIV, alcohol, and/or nutrition problems in 24 neighborhoods in
      townships in Cape Town, South Africa (n = 1,239) were randomly assigned by
      neighborhood to an intervention (Philani Plus (+), N = 12 neighborhoods; n = 645
      MAR) or a standard-care control condition of neighborhood clinic-based services
      (N = 12 neighborhoods; n = 594 MAR). Positive peer deviant "Mentor Mother" CHWs
      are recruited from the township neighborhoods and trained to deliver four
      antenatal and four postnatal home visits that address HIV, alcohol, nutrition,
      depression, health care regimens for the family, caretaking and bonding, and
      securing government-provided child grants. The MAR and their babies are being
      monitored during pregnancy, 1 week post-birth, and 6 and 18 months later. Among
      the 1,239 MAR recruited: 26% were HIV-positive; 27% used alcohol during
      pregnancy; 17% previously had low-birthweight babies; 23% had at least one
      chronic condition (10% hypertension, 5% asthma, 2% diabetes); 93% had recent
      sexual partners with 10% known to be HIV+; and 17% had clinically significant
      prenatal depression and 42% had borderline depression. This paper presents the
      intervention protocol and baseline sample characteristics for the "Philani Plus
      (+)" CHW home-visiting intervention trial.

PMID- 21850489
TI  - Do effects of mercury in larval amphibians persist after metamorphosis?
AB  - Despite widespread concern about the role of environmental contaminants in global
      amphibian declines, and evidence that post-metamorphic life stages contribute
      disproportionately to amphibian population dynamics, most studies in amphibian
      ecotoxicology focus on larval life stages. Studies that focus solely on early
      life stages may miss important effects of contaminant exposure, such as latent
      effects that manifest some time after previous exposure. Moreover, it is often
      assumed that effects observed in amphibian larvae will persist to affect survival
      or reproduction later in life. We used terrestrial enclosures to determine
      whether exposure to mercury (Hg) through maternal transfer and/or larval diet had
      any adverse effects in post-metamorphic American toads (Bufo americanus). We
      found a 5% difference in size at metamorphosis that was attributed to maternal Hg
      exposure persisted for 1 year in the terrestrial environment, resulting in a 7%
      difference at the conclusion of the study. Although patterns of survival differed
      among treatments through time, we found no overall difference in survival after 1
      year. We also found no evidence of emergent latent effects in the terrestrial
      toads that could be attributed to earlier exposure. Our results indicate that
      adverse effects of maternal Hg exposure that were observed in larval amphibians
      may persist to affect later terrestrial life stages but that no novel adverse
      effects developed when animals were raised in a semi-natural environment.
      Moreover, we found no evidence of persistent effects of dietary Hg exposure in
      larvae, highlighting a need for greater focus on maternal effects in amphibian
      ecotoxicology. Finally, we suggest an increase in the use of longitudinal studies
      to better understand contaminant impacts to amphibian populations via effects in
      both aquatic and terrestrial life stages.

PMID- 21850490
TI  - Antioxidant and anti-apoptotic activity of vasoactive intestinal peptide (VIP)
      against 6-hydroxy dopamine toxicity in the rat corpus striatum.
AB  - 6-Hydroxydopamine (6-OHDA) is an oxidative stress neurotoxin, which is oxidized
      in neurons, causes respiratory inhibition, and induces free radical formation and
      oxidative stress. Therefore, a 6-OHDA-induced Parkinson's disease (PD)
      experimental model can be used to test a candidate molecule for use as an
      antioxidant that could be a promising therapeutic for treating Parkinson's
      disease. Recent studies have shown that vasoactive intestinal peptide (VIP) might
      be a good candidate agent for the treatment of PD. In this study, the anti
      apoptotic and antioxidant actions of VIP were investigated using the 6-OHDA
      lesioned rat model for PD. Twenty-four young adult Sprague-Dawley rats were used.
      The rats were separated into the following groups: group I (n = 8), sham
      operated; group II (n = 8), 6-OHDA lesioned; group III (n = 8), 6-OHDA lesioned +
      i.p. VIP-injected (25 ng/kg) every 2 days for 15 days. The first i.p. injection
      of VIP was made 1 h after the intrastriatal 6-OHDA microinjection. Antioxidant
      enzymatic activity [super oxide dismutase (SOD) and catalase (CAT)], lipid
      peroxidation, nitric oxide and DNA fragmentation were measured from homogenates
      isolated from the corpus striatum. SOD, CAT, malondialdehyde, and DNA
      fragmentation were measured using a spectrophotometer, and nitric oxide (NO)
      levels were measured by capillary electrophoresis. 6-OHDA significantly induced
      oxidative stress, lipid peroxidation, and DNA fragmentation in the corpus
      striatum of rats. VIP significantly protected neuronal tissue from oxidative
      stress and apoptosis by reducing lipid peroxidation and DNA fragmentation. 6-OHDA
      toxicity did not cause significant changes in NO production in the corpus
      striatum. However, VIP treatment significantly reduced NO levels in brain tissue.

PMID- 21850491
TI  - Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine
      ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell
      death.
AB  - While 3,4-methylenedioxymethamphetamine (MDMA/'ecstasy') is cytostatic towards
      lymphoma cells in vitro, the concentrations required militate against its
      translation directly to a therapeutic in vivo. The possibility of 'redesigning
      the designer drug', separating desired anti-lymphoma activity from unwanted
      psychoactivity and neurotoxicity, was therefore mooted. From an initial analysis
      of MDMA analogues synthesized with a modified alpha-substituent, it was found
      that incorporating a phenyl group increased potency against sensitive, Bcl-2
      deplete, Burkitt's lymphoma (BL) cells 10-fold relative to MDMA. From this lead,
      related analogs were synthesized with the 'best' compounds (containing 1- and 2
      naphthyl and para-biphenyl substituents) some 100-fold more potent than MDMA
      versus the BL target. When assessed against derived lines from a diversity of B
      cell tumors MDMA analogues were seen to impact the broad spectrum of malignancy.
      Expressing a BCL2 transgene in BL cells afforded only scant protection against
      the analogues and across the malignancies no significant correlation between
      constitutive Bcl-2 levels and sensitivity to compounds was observed. Bcl-2
      deplete cells displayed hallmarks of apoptotic death in response to the analogues
      while BCL2 overexpressing equivalents died in a caspase-3-independent manner.
      Despite lymphoma cells expressing monoamine transporters, their pharmacological
      blockade failed to reverse the anti-lymphoma actions of the analogues studied.
      Neither did reactive oxygen species account for ensuing cell death. Enhanced
      cytotoxic performance did however track with predicted lipophilicity amongst the
      designed compounds. In conclusion, MDMA analogues have been discovered with
      enhanced cytotoxic efficacy against lymphoma subtypes amongst which high-level
      Bcl-2--often a barrier to drug performance for this indication--fails to protect.

PMID- 21850492
TI  - Vascular damage in the central nervous system: a multifaceted role for vascular
      derived TGF-beta.
AB  - The brain function depends on a continuous supply of blood. The blood-brain
      barrier (BBB), which is formed by vascular cells and glia, separates components
      of the circulating blood from neurons and maintains the precisely regulated brain
      milieu required for proper neuronal function. A compromised BBB alters the
      transport of molecules between the blood and brain and has been associated with
      or shown to precede neurodegenerative disease. Blood components immediately leak
      into the brain after mechanical damage or as a consequence of a compromised BBB
      in brain disease changing the extracellular environment at sites of vascular
      damage. It is intriguing how blood-derived components alter the cellular and
      molecular constituents of the neurovascular interface after BBB opening. We
      recently identified an unexpected role for the blood protein fibrinogen, which is
      deposited in the nervous system promptly after vascular damage, as an initial
      scar inducer by promoting the availability of active TGF-beta. Fibrinogen-bound
      latent TGF-beta interacts with astrocytes, leading to active TGF-beta formation
      and activation of the TGF-beta/Smad signaling pathway. Here, we discuss the
      pleiotropic effects of potentially vascular-derived TGF-beta on cells at the
      neurovascular interface and we speculate how these biological effects might
      contribute to degeneration and regeneration processes. Summarizing the effects of
      the components derived from the brain vascular system on nervous system
      regeneration might support the development of new therapeutic approaches.

PMID- 21850493
TI  - Engineering of vascularized adipose constructs.
AB  - Adipose tissue engineering offers a promising alternative to the current surgical
      techniques for the treatment of soft tissue defects. It is a challenge to find
      the appropriate scaffold that not only represents a suitable environment for
      cells but also allows fabrication of customized tissue constructs, particularly
      in breast surgery. We investigated two different scaffolds for their potential
      use in adipose tissue regeneration. Sponge-like polyurethane scaffolds were
      prepared by mold casting with methylal as foaming agent, whereas polycaprolactone
      scaffolds with highly regular stacked-fiber architecture were fabricated with
      fused deposition modeling. Both scaffold types were seeded with human adipose
      tissue-derived precursor cells, cultured and implanted in nude mice using a
      femoral arteriovenous flow-through vessel loop for angiogenesis. In vitro, cells
      attached to both scaffolds and differentiated into adipocytes. In vivo,
      angiogenesis and adipose tissue formation were observed throughout both
      constructs after 2 and 4 weeks, with angiogenesis being comparable in seeded and
      unseeded constructs. Fibrous tissue formation and adipogenesis were more
      pronounced on polyurethane foam scaffolds than on polycaprolactone prototyped
      scaffolds. In conclusion, both scaffold designs can be effectively used for
      adipose tissue engineering.

PMID- 21850494
TI  - Hepatorenal syndrome: are we missing some prognostic factors?
AB  - BACKGROUND: Hepatorenal syndrome (HRS) is the functional renal failure associated
      with advanced cirrhosis and has also been described in fulminant hepatic failure.
      Without liver transplantation its prognosis is dismal. Our study included
      patients with type 1 HRS associated with cirrhosis, who were not liver transplant
      candidates. AIM: To identify variables associated with improved survival.
      METHODS: Sixty-eight patients fulfilled the revised Ascites Club Criteria for
      type 1 HRS. None of them was suitable for liver transplantation. All the patients
      were treated with combinations of: albumin, midodrine and octreotide, pressors,
      and hemodialysis. RESULTS: Median survival was 13 days for the whole group.
      Survival varied with the end-stage liver disease (ESLD) etiology: autoimmune, 49
      days, cardiac cirrhosis, 22 days, idiopathic, 15.5 days, viral, 15 days,
      hepatitis C and alcohol, 14.5 days, alcohol 8 days, and neoplasia 4 days (p =
      0.048). Survival of HRS associated with alcoholic liver disease versus other
      etiologies was not statistically significant (p = 0.1). Increased serum
      creatinine (p = 0.02) and urinary sodium 6-10 mEq/l (p = 0.027) at the initiation
      of therapy were prognostic factors for mortality. HRS treatment modalities (p =
      0.73), use of dialysis (p = 0.56), dialysis modality (p = 0.35), use of
      vasopressors (p = 0.26), pre-existing renal disease (p = 0.49), gender (p =
      0.90), and age (p = 0.57) were not associated with survival. CONCLUSIONS: We
      report for the first time ESLD etiology as a prognostic factor for survival. The
      renal function (expressed as serum creatinine) and urinary Na (<5 mEq/l) at the
      time of diagnosis were found to be associated with survival, suggesting that
      early treatment might increase survival.

PMID- 21850495
TI  - Short-term supplementation with Aronia melanocarpa extract improves platelet
      aggregation, clotting, and fibrinolysis in patients with metabolic syndrome.
AB  - PURPOSE: A diet rich in berries is believed to play a distinct role in the
      prevention of metabolic diseases associated with obesity. So far, there have been
      no published clinical observations evaluating the influence of Aronia melanocarpa
      on hemostasis. The aim of our study was to investigate the effects of A.
      melanocarpa extract (AM) supplementation on platelet aggregation, clot formation,
      and lysis in patients with metabolic syndrome (MS). METHODS: Middle-aged non
      medicated subjects with MS (n = 38) and 14 healthy volunteers were included in
      this study. Patients with MS were treated with 100 mg of AM three times daily for
      2 months. RESULTS: We observed a significant reduction in the concentration of
      TC, LDL-C, and TG after AM supplementation. Beneficial changes in coagulation
      parameters were also observed. After 1 month of AM administration, we noticed
      significant inhibition of platelet aggregation. However, this effect became less
      pronounced after 2 months of supplementation. In the case of coagulation induced
      by endogenic thrombin, a significant decrease in the overall potential for
      coagulation was induced after 1 or 2 months of supplementation. Moreover, after 1
      month of AM extract supplementation, we observed a beneficial reduction in the
      overall potential for clot formation and fibrinolysis. CONCLUSIONS: We observed
      the normalization of hemostasis parameters in MS patients after both 1 and 2
      months of AM administration. After 1 month of AM supplementation, we found
      favorable changes in regards to the overall potential for plasma clotting, clot
      formation, and lysis, as well as in the lipid profiles of subjects.

PMID- 21850496
TI  - Four-week ingestion of blood orange juice results in measurable anthocyanin
      urinary levels but does not affect cellular markers related to cardiovascular
      risk: a randomized cross-over study in healthy volunteers.
AB  - PURPOSE: Blood orange juice (OJ) is an important source of anthocyanins (ACN).
      The latter molecules are endowed with antioxidant activity and might thus
      modulate different cell function. Our aim was to investigate ACN absorption
      following a 1-month daily supplementation of blood OJ and their potential effects
      on cell markers of platelet and leukocyte activation and interaction. METHODS:
      Eighteen healthy subjects (10 men and 8 women) were supplemented for 4 weeks with
      1 L/day of either blood OJ or blond OJ (that contains no ACN), following a cross
      over design. Blood samples were obtained from fasting participants both at
      baseline and after each week of treatment to measure plasma ACN concentration. At
      the same time-intervals, 24-h urinary excretion of these molecules was also
      measured. At the beginning and the end of each 4-week intervention period,
      platelet and leukocyte markers and mixed cell conjugates were assessed both in
      basal condition and upon in vitro collagen/ADP activation. RESULTS: After 1 week
      supplementation with blood OJ, 24-h urinary excretion of ACN reached average
      levels of 11.47 +/- 5.63 nmol that significantly differed from baseline and
      remained substantially unchanged until the end of treatment. No plasma
      accumulation of ACN following blood OJ supplementation was observed. Cellular
      markers were not significantly affected by either OJ after 4-week
      supplementation. CONCLUSIONS: Following supplementation of healthy volunteers
      with 1 L/day of blood OJ for 4 weeks, the ACN plasma levels reached were
      insufficient to significantly modify cell markers of platelet and leukocyte
      activation and interaction.

PMID- 21850498
TI  - Caesalpinia sappan extract inhibits IL1beta-mediated overexpression of matrix
      metalloproteinases in human chondrocytes.
AB  - Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the
      progression of osteoarthritis (OA) and represents a promising target for the
      management of OA with nutraceuticals. In this study, we sought to determine the
      MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human
      OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage
      and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1beta), without
      or with pretreatment with CSE. Following viability assays, the production of MMP
      2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP
      3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using
      RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase
      reporter construct and NF-kB p50 and p65 expression vectors in the presence or
      absence of CSE. In addition, the direct effect of CSE on the proteolytic
      activities of MMP-2 was evaluated using gelatin zymography. We found that CSE
      significantly suppressed IL1beta-mediated upregulation of MMP-13 mRNA and protein
      levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We
      further observed that the levels of IL1beta-induced MMP-1, MMP-3, MMP-7, and MMP
      9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response
      to CSE. Zymographic results suggested that CSE did not directly interfere with
      the proteolytic activity of MMP-2. In summary, this study provides evidence for
      the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA
      chondrocytes. The data indicate that the mechanism of this inhibition might, at
      least in part, involve targeting of NF-kB-mediated promoter activation.

PMID- 21850499
TI  - Reduction of artefacts caused by hip implants in CT-based attenuation-corrected
      PET images using 2-D interpolation of a virtual sinogram on an irregular grid.
AB  - PURPOSE: Metallic prosthetic replacements, such as hip or knee implants, are
      known to cause strong streaking artefacts in CT images. These artefacts likely
      induce over- or underestimation of the activity concentration near the metallic
      implants when applying CT-based attenuation correction of positron emission
      tomography (PET) images. Since this degrades the diagnostic quality of the
      images, metal artefact reduction (MAR) prior to attenuation correction is
      required. METHODS: The proposed MAR method, referred to as virtual sinogram-based
      technique, replaces the projection bins of the sinogram that are influenced by
      metallic implants by a 2-D Clough-Tocher cubic interpolation scheme performed in
      an irregular grid, called Delaunay triangulated grid. To assess the performance
      of the proposed method, a physical phantom and 30 clinical PET/CT studies
      including hip prostheses were used. The results were compared to the method
      implemented on the Siemens Biograph mCT PET/CT scanner. RESULTS: Both phantom and
      clinical studies revealed that the proposed method performs equally well as the
      Siemens MAR method in the regions corresponding to bright streaking artefacts and
      the artefact-free regions. However, in regions corresponding to dark streaking
      artefacts, the Siemens method does not seem to appropriately correct the tracer
      uptake while the proposed method consistently increased the uptake in the
      underestimated regions, thus bringing it to the expected level. This observation
      is corroborated by the experimental phantom study which demonstrates that the
      proposed method approaches the true activity concentration more closely.
      CONCLUSION: The proposed MAR method allows more accurate CT-based attenuation
      correction of PET images and prevents misinterpretation of tracer uptake, which
      might be biased owing to the propagation of bright and dark streaking artefacts
      from CT images to the PET data following the attenuation correction procedure.

PMID- 21850500
TI  - Relationship between vascular stiffness and stress myocardial perfusion imaging
      in asymptomatic patients with diabetes.
AB  - PURPOSE: Vascular stiffness may potentially be used as a screening tool to
      identify asymptomatic patients with diabetes with abnormal myocardial perfusion.
      The purpose of this study was therefore to determine the association between
      vascular stiffness, measured in term of pulse wave velocity (PWV) and
      augmentation index (AIx), and abnormal myocardial perfusion imaging (MPI) in
      asymptomatic patients with diabetes. METHODS: Prospectively, 160 asymptomatic
      patients with diabetes (mean age 51 years, 87 men) underwent MPI with adenosine
      stress. The summed stress score (SSS) was determined in each patient according to
      a 17-segment and five-point score. Abnormal MPI (SSS >= 3) was classified as
      moderate (SSS 3-7) or severe (SSS >= 8) MPI defects. Using applanation tonometry,
      the carotid-femoral PWV and the radial AIx corrected to 75 beats per minute were
      determined noninvasively. RESULTS: MPI was abnormal in 61 patients (38%), with
      severe MPI defects in 22 patients (14%). Mean PWV increased with deteriorating
      MPI from 8.4 +/- 2.2 m/s in normal MPI to 9.0 +/- 2.2 m/s in moderate MPI defects
      (p = 0.11) and to 11.1 +/- 2.5 m/s in severe MPI defects (p < 0.01). Likewise,
      mean AIx increased from 18.4 +/- 13.4% to 19.4 +/- 10.7% (p = 0.66) and to 25.4
      +/- 9.0% (p = 0.03). After adjustment for age and other risk factors, PWV
      remained a significant predictor of severe MPI defects (p = 0.01, OR 1.50, 95% CI
      1.11-2.00), whereas AIx was no longer significant (p = 0.20). CONCLUSION:
      Vascular stiffness measured by PWV is associated with severe MPI defects in
      asymptomatic patients with diabetes.

PMID- 21850501
TI  - Left ventricular diastolic dyssynchrony assessed with phase analysis of gated
      myocardial perfusion SPECT: a comparison with tissue Doppler imaging.
AB  - PURPOSE: The aim of the current study was to evaluate the feasibility of phase
      analysis on gated myocardial perfusion SPECT (GMPS) for the assessment of left
      ventricular (LV) diastolic dyssynchrony in a head-to-head comparison with tissue
      Doppler imaging (TDI). METHODS: The population consisted of patients with end
      stage heart failure of New York Heart Association functional class III or IV with
      a reduced LV ejection fraction of <= 35%. LV diastolic dyssynchrony was
      calculated using TDI as the maximal time delay between early peak diastolic
      velocities of two opposing left ventricle walls (diastolic mechanical delay).
      Significant LV diastolic dyssynchrony was defined as a diastolic mechanical delay
      of >55 ms on TDI. Furthermore, phase analysis on GMPS was performed to evaluate
      LV diastolic dyssynchrony; diastolic phase standard deviation (SD) and histogram
      bandwidth (HBW) were used as markers of LV diastolic dyssynchrony. RESULTS: A
      total of 150 patients (114 men, mean age 66.0 +/- 10.4 years) with end-stage
      heart failure were enrolled. Both diastolic phase SD (r = 0.81, p < 0.01) and
      diastolic HBW (r = 0.75, p < 0.01) showed good correlations with LV diastolic
      dyssynchrony on TDI. Additionally, patients with LV diastolic dyssynchrony on TDI
      (>55 ms) showed significantly larger diastolic phase SD (68.1 +/- 13.4 degrees 
      vs. 40.7 +/- 14.0 degrees , p < 0.01) and diastolic HBW (230.6 +/- 54.3 degrees 
      vs. 129.0 +/- 55.6 degrees , p < 0.01) as compared to patients without LV
      diastolic dyssynchrony on TDI (<= 55 ms). Finally, phase analysis on GMPS showed
      a good intra- and interobserver reproducibility for the determination of
      diastolic phase SD (ICC 0.97 and 0.88) and diastolic HBW (ICC 0.98 and 0.93).
      CONCLUSION: Phase analysis on GMPS showed good correlations with TDI for the
      assessment of LV diastolic dyssynchrony.

PMID- 21850502
TI  - "Intrinsic Roles" rather than "armour": renaming the "non-medical expert roles"
      of the CanMEDS framework to match their intent.

PMID- 21850503
TI  - Increased plasminogen activator inhibitor-1 levels in patients with isolated
      coronary artery ectasia.
AB  - Isolated coronary artery ectasia (ICAE) is defined as the ectasia of the coronary
      arteries without concomitant coronary artery stenosis. The etiology and the
      clinical course of ICAE are still not clear. Increased levels of plasminogen
      activator inhibitor-1 (PAI-1) inhibit vasa vasorum, leading to diminished vessel
      wall supply and thus contributes to aortic aneurysm expansion. Whether the same
      process has role in coronary artery ectasia is not known. The aim of this study
      is to investigate the association between PAI-1 and coronary artery ectasia in
      patients without concomitant obstructive coronary artery disease. Among 2830
      patients who underwent coronary angiography between March 2010 and 2011, 55
      patients (40 male, 15 female, mean age 60 +/- 8 years) with ICAE, formed our
      study group. 27 patients with similar patient characteristics, with
      angiographically proven normal coronary arteries, were enrolled as the control
      group. The basal characteristics were similar between two groups. PAI-1 levels
      were statistically higher in the ICAE group compared to the control group (104.13
      +/- 56.65 and 63.39 +/- 35.01 ng/dl, respectively) (P = 0.008). A significant
      positive correlation between CAE and PAI-1 (r = 0.358, P = 0.007) was also
      demonstrated. Serum high sensitive C reactive protein (hsCRP) levels did not
      differ between two groups (P > 0.05). The plasma PAI-1 levels were significantly
      higher in ICAE patients compared to normal coronary artery group. Increased PAI-1
      levels may diminish vasa vasorum by antiangiogenic activity leading to coronary
      ectasia.

PMID- 21850504
TI  - Impacts of gene bioaugmentation with pJP4-harboring bacteria of 2,4-D
      contaminated soil slurry on the indigenous microbial community.
AB  - Gene bioaugmentation is a bioremediation strategy that enhances biodegradative
      potential via dissemination of degradative genes from introduced microorganisms
      to indigenous microorganisms. Bioremediation experiments using 2,4
      dichlorophenoxyacetic acid (2,4-D)-contaminated soil slurry and strains of
      Pseudomonas putida or Escherichia coli harboring a self-transmissible 2,4-D
      degradative plasmid pJP4 were conducted in microcosms to assess possible effects
      of gene bioaugmentation on the overall microbial community structure and
      ecological functions (carbon source utilization and nitrogen transformation
      potentials). Although exogenous bacteria decreased rapidly, 2,4-D degradation was
      stimulated in bioaugmented microcosms, possibly because of the occurrence of
      transconjugants by the transfer of pJP4. Terminal restriction fragment length
      polymorphism analysis revealed that, although the bacterial community structure
      was disturbed immediately after introducing exogenous bacteria to the inoculated
      microcosms, it gradually approached that of the uninoculated microcosms. Biolog
      assay, nitrate reduction assay, and monitoring of the amoA gene of ammonia
      oxidizing bacteria and nirK and nirS genes of denitrifying bacteria showed no
      irretrievable depressive effects of gene bioaugmentation on the carbon source
      utilization and nitrogen transformation potentials. These results may suggest
      that gene bioaugmentation with P. putida and E. coli strains harboring pJP4 is
      effective for the degradation of 2,4-D in soil without large impacts on the
      indigenous microbial community.

PMID- 21850505
TI  - Changing climate, challenging choices: identifying and evaluating climate change
      adaptation options for protected areas management in Ontario, Canada.
AB  - Climate change will pose increasingly significant challenges to managers of parks
      and other forms of protected areas around the world. Over the past two decades,
      numerous scientific publications have identified potential adaptations, but their
      suitability from legal, policy, financial, internal capacity, and other
      management perspectives has not been evaluated for any protected area agency or
      organization. In this study, a panel of protected area experts applied a Policy
      Delphi methodology to identify and evaluate climate change adaptation options
      across the primary management areas of a protected area agency in Canada. The
      panel identified and evaluated one hundred and sixty five (165) adaptation
      options for their perceived desirability and feasibility. While the results
      revealed a high level of agreement with respect to the desirability of adaptation
      options and a moderate level of capacity pertaining to policy formulation and
      management direction, a perception of low capacity for implementation in most
      other program areas was identified. A separate panel of senior park agency
      decision-makers used a multiple criterion decision-facilitation matrix to further
      evaluate the institutional feasibility of the 56 most desirable adaptation
      options identified by the initial expert panel and to prioritize them for
      consideration in a climate change action plan. Critically, only two of the 56
      adaptation options evaluated by senior decision-makers were deemed definitely
      implementable, due largely to fiscal and internal capacity limitations. These
      challenges are common to protected area agencies in developed countries and
      pervade those in developing countries, revealing that limited adaptive capacity
      represents a substantive barrier to biodiversity conservation and other protected
      area management objectives in an era of rapid climate change.

PMID- 21850506
TI  - TVT-O vs. TVT for the treatment of SUI: a non-inferiority study.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to prospectively compare, in terms
      of efficacy and safety, the tension-free vaginal tape (TVT) and the
      transobturator vaginal tape inside-out (TVT-O) procedure for stress urinary
      incontinence. METHODS: A cough stress test was applied to the objective outcomes,
      while urinary incontinence-specific quality of life questionnaire was applied to
      the subjective outcomes. A test for non-inferiority was carried out for detecting
      the success rate between the two groups. RESULTS: The objective success rates
      were found to be 95.4% (62/65) in the TVT group and 96.4% (108/112) in the TVT-O
      group. No significant difference was found between these two groups in the
      success rate by non-inferiority test (P < 0.0005), with significant improvement
      in quality of life and no significant difference in patient satisfaction rates in
      the two groups (P > 0.05). CONCLUSIONS: In the study, the TVT-O procedure could
      be defined to be identical to the TVT approach in success rate by non-inferiority
      test.

PMID- 21850507
TI  - Reliability and responsiveness of the Urgency Severity and Life Impact
      Questionnaire (USIQ).
AB  - INTRODUCTION AND HYPOTHESIS: The aims of this study are (1) to assess the
      reliability (test-retest) of the Urgency Severity and Life Impact Questionnaire
      (USIQ) and (2) to test the effect of extended-release tolterodine on symptoms of
      urinary urgency using this validated instrument. METHODS: To measure reliability,
      women with overactive bladder (OAB) completed the USIQ on two separate occasions,
      prior to treatment for OAB. To assess the responsiveness, the USIQ participants
      completed the above-mentioned questionnaires prior to and following 4 weeks of
      treatment for OAB with extended-release tolterodine. RESULTS: USIQ-S and USIQ-QoL
      scores at the two visits did not differ significantly. Repeated measures of USIQ
      S and USIQ-QoL demonstrated a moderate to excellent intraclass correlation
      coefficient (0.64-0.74; P < 0.0001 and 0.48-0.91, P < 0.0001, respectively). A
      significant decrease in mean USIQ-S and USIQ-QOL (71 +/- 14 vs. 44 +/- 19, P <
      0.0001 and 51 +/- 22 vs. 39 +/- 10, P < 0.01, respectively) scores following
      treatment with tolterodine. CONCLUSIONS: This valid, reliable measure can be used
      in clinical practice and research trials to measure urgency severity.

PMID- 21850508
TI  - Vaginal hysterectomy and risk of pelvic organ prolapse and stress urinary
      incontinence surgery.
AB  - INTRODUCTION AND HYPOTHESIS: This study aims to determine the risk of pelvic
      organ prolapse (POP) and stress urinary incontinence (SUI) surgery related to
      mode of hysterectomy focusing on vaginal hysterectomy. METHODS: We performed a
      nationwide cohort study. Women exposed to hysterectomy on benign indications (n =
      118,601) were compared to women unexposed to hysterectomy (n = 579,200). The
      outcome was defined as first occurrence of POP or SUI surgery. Hazard ratios
      (HRs) were calculated with 95% confidence intervals (CIs) using Cox proportional
      hazards models. RESULTS: The greatest risks of POP (HR 4.9, 95% CI 3.4-6.9) or
      SUI surgery (HR 6.3, 95% CI 4.4-9.1) were observed subsequent to vaginal
      hysterectomy for pelvic organ prolapse. Having a vaginal hysterectomy for other
      reasons also significantly increased the risks of POP and SUI surgery compared to
      other modes of hysterectomy. CONCLUSIONS: Hysterectomy in general, in particular
      vaginal hysterectomy, was associated with an increased risk for subsequent POP
      and SUI surgery.

PMID- 21850509
TI  - Impact of birth in the presence and absence of simulated birth injury on vaginal
      glycosaminoglycan content.
AB  - INTRODUCTION AND HYPOTHESIS: This study aims to evaluate the effects of simulated
      birth trauma and vaginal and Cesarean delivery on glycosaminoglycans (GAGs) in
      the vagina of female rats. METHODS: One hundred ten rats were divided into six
      groups: A (control), B (vaginal trauma), C (Cesarean delivery), D (Cesarean
      delivery followed by vaginal trauma), E (vaginal delivery), and F (20th day of
      gestation). In each group, half of the animals were killed 4 days after the
      procedure (time 1) and 12 weeks later (time 2). GAGs were extracted, isolated,
      and identified by using agarose gel electrophoresis and quantified by
      densitometry. Statistical analysis was performed using Kruskal-Wallis and Mann
      Whitney tests. RESULTS: We observed a significant decrease in total GAGs and
      dermatan sulfate (DS) at time 1. Evaluation at time 2 showed a significant
      increase in total GAGs, DS, and heparan sulfate. CONCLUSIONS: Levels of sulfated
      GAGs in the rat vagina are affected by delivery and simulated birth trauma.

PMID- 21850510
TI  - Prevalence of urinary urgency symptoms decreases by mid-urethral sling procedures
      for treatment of stress incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Conflicting opinions on the effect of incontinence
      surgery on the prevalence of postoperative urgency symptoms exists. Our aim was
      to evaluate the prevalence of urgency symptoms preoperatively and during 3-year
      of follow-up in women undergoing mid-urethral sling procedures for stress
      incontinence. METHODS: Two hundred and sixty-seven women were randomly assigned
      to a retropubic or a transobturator operation. Detrusor instability score (DIS)
      and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to assess
      prevalence of urgency symptoms. The Incontinence Impact Questionnaire-7, visual
      analog scale, urinary incontinence severity score, and the EuroQol-5D assessed
      overall quality of life changes. RESULTS: A significant decrease in the DIS and
      UDI-6 score was seen postoperatively. Signs of de novo urgency symptoms were low.
      CONCLUSIONS: Mid-urethral sling procedures can be recommended in cases of mixed
      incontinence, and the procedures seems to decrease prevalence of urgency
      symptoms.

PMID- 21850511
TI  - Effect of plasma etching on destructive adsorption properties of polypropylene
      fibers containing magnesium oxide nanoparticles.
AB  - Dermal absorption of pesticides poses a danger for agricultural workers. Use of
      personal protection equipment (PPE) is required to provide protection; some of
      the current PPE involves impermeable barriers. In these barrier materials, the
      same mechanism that prevents the penetration of toxic chemicals also blocks the
      passage of water vapor and air from flowing through the material, making the
      garments uncomfortable. Fibers that degrade organophosphate pesticides, such as
      methyl parathion, were developed by incorporating metal oxides. These modified
      fibers can be incorporated into conventional fabric structures that allow water
      vapor to pass through, thereby maintaining comfort. Fibers with self
      decontamination functionality were developed by incorporating magnesium oxide
      (MgO) nanoparticles into a polypropylene (PP) melt-extruded fiber. These fibers
      were then treated with plasma etching to expose increased surface area of the MgO
      nanoparticles. Three steps were involved in this research project: (1)
      determining the reactivity of MgO and methyl parathion, (2) making melt-spun
      MgO/PP fibers, and (3) testing the reactivity of MgO/PP composite fibers and
      methyl parathion. It was confirmed that MgO stoichiometrically degrades methyl
      parathion by way of destructive adsorption. The etching of the PP fibers
      containing MgO nanoparticles increased the chemical accessibility of MgO reactive
      sites, therefore making them more effective in degrading methyl parathion. These
      fibers can enhance the protection provided by PPE to agricultural and
      horticultural workers and military personnel.

PMID- 21850512
TI  - Blood pressure control rates with an antihypertensive regimen including
      trandolapril in a Canadian usual-care setting.
AB  - INTRODUCTION: The aim of the study was to assess the effects on blood pressure
      (BP) levels and control rates in hypertensive subjects receiving trandolapril as
      monotherapy or as part of an antihypertensive regimen in everyday Canadian
      clinical practice. METHODS: The MAVIKtory study was a multicenter, single-arm
      observational study in 601 primary-care centers in Canada. Diabetic and
      nondiabetic subjects were included, who were treated with trandolapril for
      hypertension in accordance with usual practices and national guidelines. Subjects
      received trandolapril as a new prescription, alone, or in combination with prior
      therapy. Treatment regimens were at the discretions of the treating physicians.
      Subjects were followed for 6 months. The primary outcomes measures were the
      percentage of subjects reaching BP targets set by their physicians after 6 months
      of therapy, and the percentage of subjects reaching the guidelines targets
      (systolic blood pressure [SBP]/diastolic blood pressure [DBP] < 140/90 mm Hg)
      after 6 months as assessed by their physicians. Other outcomes were the
      percentage of diabetic subjects reaching BP targets, and tolerability. RESULTS: A
      total of 8787 subjects were enrolled and included in the intention-to-treat
      population. Starting doses of trandolapril were 1 or 2 mg in the majority of
      subjects and remained unchanged in 51.9% of the population at 6 months. The
      target of < 140/90 (< 130/80) mm Hg was reached by 67.3% of the population. The
      lower mean physician-set target of 133.4/83.3 mm Hg for nondiabetic subjects and
      128.6/79.3 mm Hg for diabetic subjects was reached by 52.2%. Mean reductions from
      baseline to month 6 were 19.4 mm Hg (95% CI: [-19.9 to -19.0]) in SBP, and 10.1
      mm Hg (95% CI: [-10.4 to -9.8]) in DBP. Cough was the most commonly reported
      adverse event, reported in 4.2% of all subjects. CONCLUSION: Trandolapril
      demonstrated a favorable safety and effectiveness profile. SBP reductions of
      approximately 20 mm Hg and control rates > 65% could be achieved over 6 months.

PMID- 21850513
TI  - Hydroxyapatite-anatase-carbon nanotube nanocomposite coatings fabricated by
      electrophoretic codeposition for biomedical applications.
AB  - In order to eliminate micro-cracks in the monolithic hydroxyapatite (HA) and
      composite hydroxyapatite/carbon nanotube (HA/CNT) coatings, novel HA/TiO(2)/CNT
      nanocomposite coatings on Ti6Al4V were attempted to fabricate by a single-step
      electrophoretic codeposition process for biomedical applications. The
      electrophoretically deposited layers with difference contents of HA, TiO(2)
      (anatase) and CNT nanoparticles were sintered at 800 degrees C for densification
      with thickness of about 7-10 MUm. A dense and crack-free coating was achieved
      with constituents of 85 wt% HA, 10 wt% TiO(2) and 5 wt% CNT. Open-circuit
      potential measurements and cyclic potentiodynamic polarization tests were used to
      investigate the electrochemical corrosion behavior of the coatings in vitro
      conditions (Hanks' solution at 37 degrees C). The HA/TiO(2)/CNT coatings possess
      higher corrosion resistance than that of the Ti6Al4V substrate as reflected by
      nobler open circuit potential and lower corrosion current density. In addition,
      the surface hardness and adhesion strength of the HA/TiO(2)/CNT coatings are
      higher than that of the monolithic HA and HA/CNT coatings without compromising
      their apatite forming ability. The enhanced properties were attributed to the
      nanostructure of the coatings with the appropriate TiO(2) and CNT contents for
      eliminating micro-cracks and micro-pores.

PMID- 21850514
TI  - Barriers to quitting smoking among medically ill smokers.
AB  - Few studies examine predictors of smoking cessation among medically ill smokers,
      despite their high smoking prevalence. We prospectively examined barriers to
      smoking cessation in medically ill smokers, with age as a hypothesized moderator.
      Participants were smokers (N = 237, M (age) = 56.1, 53.6% females) receiving home
      based nursing care. Baseline self-report questionnaires assessed barriers to
      cessation (demographics, smoking history, psychosocial, and medical factors).
      Smoking status was biochemically verified at 2- and 6-months post-intervention.
      Compared with younger smokers, older smokers had significantly lower levels of
      nicotine dependence, stress, and depressed mood and a greater prevalence of
      smoking-related diseases. Older smokers were more likely to achieve biochemically
      verified abstinence at 6-month follow-up (7.8%) than younger smokers (3.1%)
      though this difference was not significant. Higher levels of depressed mood and
      lower levels of perceived stress were associated with a greater likelihood of
      cessation at both follow-up points, but only for younger smokers. For younger
      smokers, higher self-efficacy to quit and the presence of a smoking-related
      disease increased the odds of abstinence. These findings could help guide
      treatment development for this high-risk group of smokers.

PMID- 21850515
TI  - Choice and placebo expectation effects in the context of pain analgesia.
AB  - The current experiment examined whether having choice over treatment options
      facilitates or inhibits the strength of placebo expectations in the context of
      pain perception. All participants were exposed to an aversive stimulus (i.e., the
      cold pressor task), and participants in some conditions were given expectations
      for two pain-relieving treatments (actually the same inert ointment mixture).
      Critically, participants in these expectation conditions were also given a choice
      or not about which of the two treatments they preferred to use. Participants in a
      control condition were not provided with a treatment expectation. Despite
      receiving the same inert treatment, participants who had a choice over treatments
      showed increased placebo analgesia as compared to participants not given a choice
      and participants in the control condition. Moreover, this effect was mediated by
      changes in anxiety. Explanations and implications for these results are
      discussed.

PMID- 21850516
TI  - An affective booster moderates the effect of gain- and loss-framed messages on
      behavioral intentions for colorectal cancer screening.
AB  - Previous research has demonstrated that loss-framed messages are more effective
      than gain-framed messages in motivating detection behaviors such as screening.
      The present study examined whether affective context moderates the degree to
      which message frame is associated with behavioral intentions to engage in
      colorectal cancer screening. In particular, we buttressed a framing manipulation
      with an "affective booster" to increase anticipated and anticipatory emotions
      associated with the framed messages. Consistent with previous research, we found
      that loss-framed messages are more effective in increasing intentions to screen.
      However, we found that among individuals who received gain-framed messages (but
      not loss-framed messages), the affective booster increased message
      persuasiveness. This effect on intentions was partially mediated by self-efficacy
      for engaging in screening. This study indicates that in the presence of emotional
      boosters, loss-framed messages may lose their advantage over gain-framed messages
      in motivating detection behaviors, and that self-efficacy may partially explain
      these effects.

PMID- 21850517
TI  - Renal function and endocrine responses to arm exercise in euhydrated individuals
      with spinal cord injury.
AB  - This study investigated the renal and endocrine responses to arm exercise in
      persons with spinal cord injury (SCI) under euhydration conditions (ad libitum
      drinking of water) and determined the physiological effects of exercise on renal
      function in these subjects. Eleven SCI (spinal lesions between T6 and L1,
      American Spinal Injury Association impairment scale A) and 14 able-bodied (AB)
      persons first rested for 1 h in a sitting position, before undergoing 2-h arm
      crank ergometer exercise at 60% of maximum oxygen consumption followed by a 2-h
      recovery period. On another day, all subjects participated in a time control
      study (5 h of rest condition in sitting position). Urine and blood samples were
      collected hourly. There were no differences in mean blood pressure between the
      two groups. SCI patients showed attenuated increase in plasma adrenaline and
      increase in plasma aldosterone compared with AB controls, but similar changes in
      human atrial natriuretic polypeptide, plasma renin activity and plasma
      antidiuretic hormone following the exercise. Creatinine clearance, osmolal
      clearance, free water clearance and fractional excretion of Na(+) did not change
      during exercise in any of the subjects. These findings suggested that activated
      aldosterone and attenuated adrenaline responses during exercise in SCI could be
      due to adaptation to disordered sympathetic nervous system triggered to maintain
      renal function. The results showed no exercise-related adverse effects on renal
      function in hydrated subjects with SCI.

PMID- 21850518
TI  - An additional suture secures against pitfalls in delta-shaped gastroduodenostomy
      after laparoscopic distal gastrectomy.
AB  - Laparoscopic gastrectomy is widely used as a minimally invasive surgery for
      gastric cancer. Laparoscopic distal gastrectomy must be followed by either a
      gastroduodenostomy or gastrojejunostomy to restore continuity of the alimentary
      tract. The intraabdominal delta-shaped gastroduodenostomy using endoscopic linear
      staplers, which was developed by Kanaya et al., is one of the feasible
      reconstructive procedures. However, the clinical results still remain uncertain.
      In 71 patients treated between February 2008 and February 2009, we found that
      anastomotic failure occurred in six patients and there was an intraabdominal
      abscess around the anastomosis in two patients, findings which might be
      associated with technical pitfalls in the procedure. After considering the
      mechanisms underlying these unfavorable complications, we developed a
      modification of the procedure to successfully overcome these complications by
      reinforcement of the anastomosis using simple suturing at the closed common
      channel on the greater curvature. This modified Kanaya's procedure will be safer
      and should provide a better intracorporeal gastroduodenostomy after laparoscopic
      distal gastrectomy.

PMID- 21850519
TI  - A user-friendly guide on how to obtain and accurately interpret information from
      metabolic databases.

PMID- 21850520
TI  - SNAP-25 contains non-acylated thiol pairs that can form intrachain disulfide
      bonds: possible sites for redox modulation of neurotransmission.
AB  - Intrachain disulfide bond formation among the cysteine thiols of SNAP-25, a
      component of the SNARE protein complex required for neurotransmitter release, has
      been hypothesized to link oxidative stress and inhibition of synaptic
      transmission. However, neither the availability in vivo of SNAP-25 thiols, which
      are known targets of S-palmitoylation, nor the tendency of these thiols to form
      intrachain disulfide bonds is known. We have examined, in rat brain extracts,
      both the availability of closely spaced, or vicinal, thiol pairs in SNAP-25 and
      the propensity of these dithiols toward disulfide bond formation using a method
      improved by us recently that exploits the high chemoselectivity of phenylarsine
      oxide (PAO) for vicinal thiols. The results show for the first time that a
      substantial fraction of soluble and, to a lesser extent, particulate SNAP-25
      contain non-acylated PAO-binding thiol pairs and that these thiols in soluble
      SNAP-25 in particular have a high propensity toward disulfide bond formation.
      Indeed, disulfide bonds were detected in a small fraction of soluble SNAP-25 even
      under conditions designed to prevent or greatly limit protein thiol oxidation
      during experimental procedures. These results provide direct experimental support
      for the availability, in a subpopulation of SNAP-25, of vicinal thiols that may
      confer on one or more isoforms of this family of proteins a sensitivity to
      oxidative stress.

PMID- 21850522
TI  - Multiple perspectives on mental health outcome: needs for care and service
      satisfaction assessed by staff, patients and family members.
AB  - PURPOSE: Community-based mental health care requires the involvement of staff,
      patients, and their family members when both planning intervention programmes and
      evaluating mental health outcomes. The present study aimed to compare the
      perceptions of these three groups on two important subjective mental health
      outcome measures--needs for care and service satisfaction--to identify potential
      areas of discrepancy. METHODS: The sample consisted of patients with a DSM
      diagnosis of psychosis and attending either outpatient or day centres operating
      in a community-based care system. Staff, patients and family members were
      assessed by using the CAN and the VSSS to evaluate, respectively, needs for care
      and service satisfaction. Kappa statistics were computed to assess agreement in
      the three groups. RESULTS: Patients identified significantly fewer basic (e.g.
      daytime activities, food, accommodation) and functioning needs (e.g. self-care,
      looking after home, etc.) than staff or family members. Only fair levels of
      agreement were found in the three groups (average kappa was 0.48 for staff and
      patients, 0.54 for staff and family members, and 0.45 for patients and
      relatives), with patients and family members showing more areas of discrepancies
      in both needs and service satisfaction. CONCLUSIONS: These findings provide
      further support for the idea that mental health services should routinely involve
      patients and their relatives when planning and evaluating psychiatric
      intervention and that this policy is a premise for developing a partnership care
      model.

PMID- 21850523
TI  - Increased oxidative stress and cytotoxicity by hydrogen sulfide in HepG2 cells
      overexpressing cytochrome P450 2E1.
AB  - The main objectives of this work were to evaluate the effects of hydrogen sulfide
      on oxidative stress and cytotoxicity parameters in HepG2 cells and to assess the
      extent to which cytochrome P450 2E1 (CYP2E1) activity modulates the effects of
      hydrogen sulfide on oxidative stress and cytotoxicity. Sodium hydrosulfide (NaHS)
      caused time- and concentration-dependent cytotoxicity in both non-P450-expressing
      HepG2 cells (C34 cells) and CYP2E1-overexpressing HepG2 cells (E47 cells);
      however, NaHS-dependent cytotoxicity was higher in E47 than C34 cells.
      Cytotoxicity by NaHS in C34 and E47 cells was mainly necrotic in nature and
      associated with an early decrease in mitochondrial membrane potential. NaHS
      caused increased oxidation of lipophilic (C11-BODIPY(581/591)) and hydrophilic
      (DCFH-DA) probes only in E47 cells, at a time point prior to overt cytotoxicity.
      Trolox, an amphipathic antioxidant, partially inhibited both the cytotoxicity and
      the increased oxidative stress detected in E47 cells exposed to NaHS. Cell
      permeable iron chelators and CYP2E1 inhibitors significantly inhibited the
      oxidation of C11-BODIPY(581/591) in E47 cells in the presence of NaHS. NaHS
      produced lipid peroxidation and cytotoxicity in E47 cells supplemented with a
      representative polyunsaturated fatty acid (docosahexaenoic acid) but not in C34
      cells; these effects were inhibited by alpha-tocopherol, a lipophilic
      antioxidant. These data suggest that CYP2E1 enhances H(2)S-dependent cytotoxicity
      in HepG2 cells through the generation of iron-dependent oxidative stress and
      lipid peroxidation.

PMID- 21850524
TI  - Absence of snow cover reduces understory plant cover and alters plant community
      composition in boreal forests.
AB  - Snow regimes affect biogeochemistry of boreal ecosystems and are altered by
      climate change. The effects on plant communities, however, are largely unexplored
      despite their influence on relevant processes. Here, the impact of snow cover on
      understory community composition and below-ground production in a boreal Picea
      abies forest was investigated using a long-term (8-year) snow cover manipulation
      experiment consisting of the treatments: snow removal, increased insulation
      (styrofoam pellets), and control. The snow removal treatment caused longer (118
      vs. 57 days) and deeper soil frost (mean minimum temperature -5.5 vs. -2.2
      degrees C) at 10 cm soil depth in comparison to control. Understory species
      composition was strongly altered by the snow cover manipulations; vegetation
      cover declined by more than 50% in the snow removal treatment. In particular, the
      dominant dwarf shrub Vaccinium myrtillus (-82%) and the most abundant mosses
      Pleurozium schreberi (-74%) and Dicranum scoparium (-60%) declined strongly. The
      C:N ratio in V. myrtillus leaves and plant available N in the soil indicated no
      altered nitrogen nutrition. Fine-root biomass in summer, however, was negatively
      affected by the reduced snow cover (-50%). Observed effects are attributed to
      direct frost damage of roots and/ or shoots. Besides the obvious relevance of
      winter processes on plant ecology and distribution, we propose that shifts in the
      vegetation caused by frost damage may be an important driver of the reported
      alterations in biogeochemistry in response to altered snow cover. Understory
      plant performance clearly needs to be considered in the biogeochemistry of boreal
      systems in the face of climate change.

PMID- 21850525
TI  - MRI shows a region-specific pattern of atrophy in spinocerebellar ataxia type 2.
AB  - In this study, we used manual delineation of high-resolution magnetic resonance
      imaging (MRI) to determine the spatial and temporal characteristics of the
      cerebellar atrophy in spinocerebellar ataxia type 2 (SCA2). Ten subjects with
      SCA2 were compared to ten controls. The volume of the pons, the total cerebellum,
      and the individual cerebellar lobules were calculated via manual delineation of
      structural MRI. SCA2 showed substantial global atrophy of the cerebellum.
      Furthermore, the degeneration was lobule specific, selectively affecting the
      anterior lobe, VI, Crus I, Crus II, VIII, uvula, corpus medullare, and pons,
      while sparing VIIB, tonsil/paraflocculus, flocculus, declive, tuber/folium,
      pyramis, and nodulus. The temporal characteristics differed in each cerebellar
      subregion: (1) duration of disease: Crus I, VIIB, VIII, uvula, corpus medullare,
      pons, and the total cerebellar volume correlated with the duration of disease;
      (2) age: VI, Crus II, and flocculus correlated with age in control subjects; and
      (3) clinical scores: VI, Crus I, VIIB, VIII, corpus medullare, pons, and the
      total cerebellar volume correlated with clinical scores in SCA2. No correlations
      were found with the age of onset. Our extrapolated volumes at the onset of
      symptoms suggest that neurodegeneration may be present even during the
      presymptomatic stages of disease. The spatial and temporal characteristics of the
      cerebellar degeneration in SCA2 are region specific. Furthermore, our findings
      suggest the presence of presymptomatic atrophy and a possible developmental
      component to the mechanisms of pathogenesis underlying SCA2. Our findings further
      suggest that volumetric analysis may aid in the development of a non-invasive,
      quantitative biomarker.

PMID- 21850527
TI  - [Effectiveness of treatment for traumatic optic neuropathy].

PMID- 21850526
TI  - Diversity of the KIR gene cluster in an urban Brazilian population.
AB  - The activity of natural killer cells depends on the balance between activating
      and inhibitory signals coming from their receptors. Among these are the killer
      cell immunoglobulin-like receptors (KIR) that recognize specific HLA class I
      allotypes. Here we characterized KIR genetic diversity and their HLA ligands in
      the population of Curitiba, Parana State (n = 164), and compared it with other
      worldwide populations. The distribution of 2DL4 alleles was also analyzed. The
      Curitiba population did not differ significantly from European and Euro
      descendant populations, but as an admixed population showed higher genetic
      diversity. We found 27 KIR profiles, many of them uncommon in European
      populations, in agreement with the elevated historically recent gene flow in the
      study population. The frequencies of KIR genes and their respective HLA ligands
      were distributed independently and none of the analyzed individuals lacked
      functional KIR-HLA ligand combinations. KIR gene frequencies of 33 worldwide
      populations were consistent with geographic and ethnic distribution, in agreement
      with demography being the major factor shaping the observed gene content
      diversity of the KIR locus.

PMID- 21850528
TI  - Maximum likelihood analysis of semicompeting risks data with semiparametric
      regression models.
AB  - The "semicompeting risks" include a terminal event and a non-terminal event. The
      terminal event may censor the non-terminal event but not vice versa. Because
      times to the two events are usually correlated, the non-terminal event is subject
      to dependent/informative censoring by the terminal event. We seek to conduct
      marginal regressions and joint association analyses for the two event times under
      semicompeting risks. The proposed method is based on the modeling setup where the
      semiparametric transformation models are assumed for marginal regressions, and a
      copula model is assumed for the joint distribution. We propose a nonparametric
      maximum likelihood approach for inferences, which provides a martingale
      representation for the score function and an analytical expression for the
      information matrix. Direct theoretical developments and computational
      implementation are allowed for the proposed approach. Simulations and a real data
      application demonstrate the utility of the proposed methodology.

PMID- 21850530
TI  - Cystatin C is not a reliable marker of residual glomerular filtration rate during
      continuous renal replacement therapy.

PMID- 21850531
TI  - Assessing adrenal insufficiency of corticosteroid secretion using free versus
      total cortisol levels in critical illness.
AB  - PURPOSE: To study the value of free versus total cortisol levels in assessing
      relative adrenal insufficiency during critical illness-related corticosteroid
      insufficiency. METHODS: A prospective study in a mixed intensive care unit from
      2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with
      treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH)
      test (250 MUg) was performed. Serum total and free cortisol (equilibrium
      dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed.
      RESULTS: Although a low CBG resulted in a high free cortisol level relative to
      total cortisol, free and total cortisol and their increases were well correlated
      (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and
      free cortisol, and increases in total cortisol upon ACTH predicted increases in
      free cortisol regardless of low binding proteins. In non-sepsis, total cortisol
      was lower with than without hypoalbuminemia; free cortisol did not differ, since
      hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended
      less on binding proteins than on raw levels. The areas under the receiver
      operating characteristic curve for predicting increases in free from total
      cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower
      for sepsis vs. non-sepsis). CONCLUSIONS: Although the biologically active free
      cortisol fraction depends on binding proteins, total cortisol correlates to free
      cortisol in treatment-insensitive hypotension during critical illness. In sepsis,
      albumin is not an important binding molecule. Subnormal increments in total
      cortisol upon ACTH suffice in assessing relative adrenal insufficiency,
      particularly in sepsis.

PMID- 21850532
TI  - Limiting the spread of highly resistant hospital-acquired microorganisms via
      critical care transfers: a simulation study.
AB  - PURPOSE: Hospital-acquired infections with highly resistant organisms are an
      important problem among critically ill patients. Control of these organisms has
      largely focused within individual hospitals. We examine the extent to which
      transfers of critically ill patients could be a vector for the wide spread of
      highly resistant organisms, and compare the efficiency of different approaches to
      targeting infection control resources. METHODS: We analyzed the network of
      interhospital transfers of intensive care unit patients in 2005 US Medicare data
      and 2004-2006 Pennsylvania all-payer data. We simulated the spread of highly
      resistant hospital-acquired infections by randomly choosing a single hospital to
      develop a highly resistant organism and following the spread of infection or
      colonization throughout the network under varying strategies of infection control
      and varying levels of infectivity. RESULTS: Critical care transfers could spread
      a highly resistant organism between any two US hospitals in a median of 3 years.
      Hospitals varied substantially in their importance to limiting potential spread.
      Targeting resources to a small subset of hospitals on the basis of their position
      in the transfer network was 16 times more efficient than distributing infection
      control resources uniformly. Within any set of targeted hospitals, the best
      strategy for infection control heavily concentrated resources at a few
      particularly important hospitals, regardless of level of infectivity.
      CONCLUSIONS: Critical care transfers provide a plausible vector for widespread
      dissemination of highly resistant hospital-acquired microorganisms. Infection
      control efforts can be made more efficient by selectively targeting hospitals
      most important for transmission.

PMID- 21850533
TI  - High dose methylprednisolone counteracts the negative effects of rocuronium on
      diaphragm function.
AB  - PURPOSE: We previously showed that rocuronium combined with 24 h of controlled
      mechanical ventilation (CMV) leads to an additional negative effect on diaphragm
      function in rats. Based on clinical observations we examined whether the
      combination of rocuronium with corticosteroids during CMV would result into a
      further deterioration of diaphragm function. METHODS: Mechanically ventilated
      rats received intravenously a continuous infusion of saline (CMV) or rocuronium
      (ROC) or rocuronium combined with an intramuscular injection of 80 mg/kg of
      methylprednisolone (ROC-MP). After 24 h we determined diaphragm in vitro
      contractile properties, cross-sectional area (CSA) of the different fiber types,
      the MyHC/actin ratio, and proteolytic activity in diaphragm and gastrocnemius.
      RESULTS: ROC treatment resulted in a significant reduction of diaphragm force
      compared with CMV. Treatment with MP attenuated the ROC-induced diaphragmatic
      contractile dysfunction. CSA of the diaphragm type IIx/b fibers tended to
      decrease by 13% after ROC but not after MP. Diaphragm MuRF-1 mRNA expression
      increased significantly with 30% after ROC and ROC-MP compared to CMV, while
      MAFbx was similar in all groups. Diaphragm caspase-3 (+39%) and calpain activity
      (+99%) were increased after ROC compared to CMV. Treatment with MP abolished the
      increase in both activities. Proteolytic activity in the gastrocnemius was
      similar in all groups. The MyHC/actin ratio was similar in the diaphragm and the
      gastrocnemius in all groups. CONCLUSIONS: The combination of ROC with a high dose
      of MP attenuated diaphragm dysfunction caused by ROC probably through inhibition
      of the calpain and caspase-3 system. None of these treatments affected the
      gastrocnemius.

PMID- 21850534
TI  - Comparative effects of recombinant human activated protein C and dexamethasone in
      experimental septic shock.
AB  - PURPOSE: To compare the effects of recombinant human activated protein C (APC)
      and glucocorticoids alone and in combination in non-anesthetized resuscitated
      septic shock induced by cecal ligation and puncture (CLP) on (a) survival, (b)
      hemodynamics, and (c) vascular reactivity. The effects of treatments on major
      cellular pathways likely implicated were also studied. METHODS: Four hours after
      CLP, rats were continuously infused with either saline (10 ml/kg/h), saline +
      APC, saline + dexamethasone (Dexa), or saline + APC + Dexa. Eighteen hours after
      CLP, arterial pressure, cardiac output, nitrite/nitrate ratio, and lactate
      concentrations were measured. Aortic rings and mesenteric arteries were isolated
      and mounted in a myograph, after which arterial contractility and endothelium
      dependent relaxation were measured in the presence or absence of nitric oxide
      synthase (NOS) or cyclooxygenase (COX) inhibitors. Protein expression was
      assessed by Western blotting. Aorta NO and superoxide anion content were measured
      by electron paramagnetic resonance. RESULTS: All treatments improved hemodynamic
      parameters and vascular reactivity and decreased lactate and nitrite/nitrate
      levels. In treated aorta and mesenteric arteries, contractility and endothelial
      dysfunction were improved. This effect was associated with an increase in the
      phosphorylated form of protein kinase B as well as an increase in COX
      vasodilatory pathways and a decrease in iNOS expression suggesting that these
      pathways are implicated in the vascular effect of the treatments. CLP was
      associated with a marked increase in aortic NO and superoxide anion content (p <
      0.05), which were decreased by APC and Dexa and totally abolished by APC + Dexa
      (p < 0.01). Survival length was significantly increased by the APC-Dexa
      combination. CONCLUSIONS: Both APC and Dexa improve arterial contractility and
      endothelial dysfunction resulting from septic shock in rats. Moreover, their
      combination increased the length of survival. These findings provide important
      insights into the mechanisms underlying APC- and/or Dexa-induced improvements of
      arterial dysfunction during septic shock.

PMID- 21850536
TI  - Is there a role for high dose chemotherapy with hematopoietic stem cell rescue in
      patients with relapsed supratentorial PNET?
AB  - Supratentorial primitive neuroectodermal tumors (sPNET) are rare childhood brain
      tumors. There is no standard strategy for treating relapsed sPNETs. The role of
      high dose chemotherapy with hematopoietic stem cell rescue (HDC with HSCR) in
      treating relapsed sPNET is controversial. A systematic review of the literature
      regarding outcome of patients with relapsed sPNET treated with HDC and HSCR was
      performed to examine the potential predictive factors that would justify its use
      in this subset of patients. Forty-six patients were identified fulfilling the
      inclusion criteria. Of those, 15 patients were infants and 15 were
      pineoblastomas. With a median follow-up of 40 months (range 3-123 months) 15
      patients were reported alive. Thirteen patients out of the 15 survivors did not
      receive craniospinal irradiation (CSRT). The 12 month overall survival (OS) of
      the cohort was 44.2 +/- 7.5 months. Twelve-month OS for children less than 36
      months was 66.7 +/- 12.2 months while for older children it was 27.8 +/- 10.6 (P
      = 0.003). Twelve-month OS was 20.0 +/- 10.3 for those patients with pineoblastoma
      versus 54.6 +/- 9.0 for those with non-pineal sPNETs (P < 0.001). Cox regression
      analysis revealed pineal location as the only independent adverse prognostic
      factor. In conclusion high dose chemotherapy with HSCR might lead to survival
      primarily in younger children with relapsed sPNET even in the absence of
      concomitant use of radiotherapy, whereas the outcome in older children and/or in
      pineal location is extremely poor with this modality.

PMID- 21850537
TI  - Expression profile of frizzled receptors in human medulloblastomas.
AB  - Secreted WNT proteins signal through ten receptors of the frizzled (FZD) family.
      Because of the relevance of the WNT/beta-catenin (CTNNB1) signaling pathway in
      medulloblastomas (MBs), we investigated the expression of all ten members of the
      FZD gene family (FZD1-10) in 17 human MBs, four MB cell lines and in normal human
      cerebellum, using real-time PCR. We found that FZD2 transcript was over-expressed
      in all MBs and MB cell lines. Western blot analysis confirmed the expression of
      FZD2 at the protein level. Moreover, the levels of FZD2 transcript were found to
      correlate with those of ASPM transcript, a marker of mitosis essential for
      mitotic spindle function. Accordingly, ASPM mRNA was expressed at a very low
      level in the adult, post-mitotic, human cerebellum, at higher levels in fetal
      cerebellum and at highest levels in MB tissues and cell lines. Unlike FZD2, the
      other FZDs were overexpressed (e.g., FZD1, FZD3 and FZD8) or underexpressed
      (e.g., FZD7, FZD9 and FZD10) in a case-restricted manner. Interestingly, we did
      not find any nuclear immuno-reactivity to CTNNB1 in four MBs over-expressing both
      FZD2 and other FZD receptors, confirming the lack of nuclear CTNNB1 staining in
      the presence of increased FZD expression, as in other tumor types. Overall, our
      results indicate that altered expression of FZD2 might be associated with a
      proliferative status, thus playing a role in the biology of human MBs, and
      possibly of cerebellar progenitors from which these malignancies arise.

PMID- 21850535
TI  - Physical exercise alleviates ADHD symptoms: regional deficits and development
      trajectory.
AB  - The heterogeneous, chronic, and proliferating aspect of attention deficit
      hyperactivity disorder (ADHD) and comorbidities covers heritability, cognitive,
      emotional, motor, and everyday behavioral domains that place individuals
      presenting the condition at some considerable disadvantage. Disruption of
      "typical developmental trajectories" in the manifestation of gene-environment
      interactive predispositions implies that ADHD children and adolescents may
      continue to perform at defective levels as adults with regard to academic
      achievement, occupational enterprises, and interpersonal relationships, despite
      the promise of pharmacotherapeutic treatments. Physical exercise provides a
      plethora of beneficial effects against stress, anxiety, depression, negative
      affect and behavior, poor impulse control, and compulsive behavior concomitant
      with improved executive functioning, working memory and positive affect, as well
      as improved conditions for relatives and care-givers. Brain-derived neurotrophic
      factor, an essential element in normal brain development that promotes health
      associated behaviors and quality-of-life, though reduced in ADHD, is increased
      markedly by the intervention of regular physical exercise. Functional, regional,
      and biomarker deficits, as well as hypothalamic-pituitary-adrenal disruptions,
      have been improved through regular and carefully applied exercise programs. In
      view of the complications involving ADHD with co-morbidities, such as obesity,
      the influence of regular physical exercise has not been found negligible.
      Physical exercise bestows a propensity for eventual manifestation of
      "redifferentiated" developmental trajectories that may equip ADHD adults with a
      prognosis that is more adaptive functionally, independent of the applications of
      other therapeutic agents and treatments.

PMID- 21850538
TI  - [Urinary tract infections].
AB  - Urinary tract infections occur very frequently in the community and in
      hospitalized patients and are mainly caused by Escherichia (E.) coli. Depending
      on virulence determinants of uropathogenic microorganisms and host-specific
      defense mechanisms, urinary tract infections can manifest as cystitis,
      pyelonephritis (bacterial interstitial nephritis), bacteremia or urosepsis.
      Uncomplicated urinary tract infections in otherwise healthy women should be
      treated for 3-7 days depending on the antibiotic therapy chosen, even if
      spontaneous remission rates of up to 40% have been reported. Antibiotics of the
      first choice for empirical treatment of uncomplicated urinary tract infection are
      fluoroquinolones, pivmecillinam and fosfomycin. A huge problem is the increasing
      antimicrobial resistance of uropathogenic microorganisms. Complicated urinary
      tract infections associated with anatomical and/or functional abnormalities of
      the urinary tract and/or comorbidities such as diabetes or immunosuppressive
      therapy, need longer antibiotic treatment (e.g. 10-14 days) as well as
      interdisciplinary diagnostic procedures. Treatment of community acquired
      urosepsis includes cephalosporins of the third generation,
      piperacillin/tazobactam or ciprofloxacin. For nosocomial urosepsis the
      combination with an aminoglycoside or a carbapenem is recommended.

PMID- 21850540
TI  - Cardiac remodeling and subcellular defects in heart failure due to myocardial
      infarction and aging.
AB  - Although several risk factors including hypertension, cardiac hypertrophy,
      coronary artery disease, and diabetes are known to result in heart failure,
      elderly subjects are more susceptible to myocardial infarction and more likely to
      develop heart failure. This article is intended to discuss that cardiac
      dysfunction in hearts failing due to myocardial infarction and aging is
      associated with cardiac remodeling and defects in the subcellular organelles such
      as sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils. Despite some
      differences in the pattern of heart failure due to myocardial infarction and
      aging with respect to their etiology and sequence of events, evidence has been
      presented to show that subcellular remodeling plays a critical role in the
      occurrence of intracellular Ca(2+)-overload and development of cardiac
      dysfunction in both types of failing heart. In particular, alterations in gene
      expression for SL and SR proteins induce Ca(2+)-handling abnormalities in
      cardiomyocytes, whereas those for myofibrillar proteins impair the interaction of
      Ca(2+) with myofibrils in hearts failing due to myocardial infarction and aging.
      In addition, different phosphorylation mechanisms, which regulate the activities
      of Ca(2+)-cycling proteins in SL and SR membranes as well as Ca(2+)-binding
      proteins in myofibrils, become defective in the failing heart. Accordingly, it is
      suggested that subcellular remodeling involving defects in Ca(2+)-handling and
      Ca(2+)-binding proteins as well as their regulatory mechanisms is intimately
      associated with cardiac remodeling and heart failure due to myocardial infarction
      and aging.

PMID- 21850543
TI  - Interference of IP-10 expression inhibits vascular smooth muscle cell
      proliferation and intimal hyperplasia in carotid artery: a new insight in the
      prevention of restenosis.
AB  - After vascular angioplasty, vascular smooth muscle cell (VSMC) proliferation
      causes atherosclerosis and intimal hyperplasia leading to restenosis. Interferon
      gamma-inducible protein (IP)-10 plays a role in atherogenesis, but the mechanism
      remains unclear. We evaluated the role of IP-10 in intimal hyperplasia and
      restenosis. IP-10 expression was determined in arterial specimens from 20
      arteriosclerotic obliteration patients and 6 healthy individuals. VSMCs were
      stimulated in vitro with IFN-gamma and transfected with IP-10 siRNA. Silencing
      was verified with RT-PCR/Western blot; cell proliferation rate was detected by
      methyl-thiazol-tetrazolium. The carotid artery model of atherosclerosis injury
      was established with IP-10 siRNA. IP-10 expression was detected at 1 and 4 weeks
      using RT-PCR and immunohistochemistry. Artery morphology was assessed with
      hematoxylin-and-eosin staining, and intimal hyperplasia was evaluated by electron
      microscopy. IP-10 was overexpressed in arteriosclerotic obliteration group
      compared with control group (P < 0.05). IP-10 expression in transfected group was
      significantly lower than in untransfected group. The intima-to-media ratio of
      transfected group at 4 weeks was lower than that of untransfected group (P <
      0.01). The transfected group exhibited more regular intimal structure and less
      hyperplasia under electron microscopy. We, therefore, concluded that IP-10 played
      an important role in intimal hyperplasia as siRNA-mediated IP-10 silencing
      inhibited aberrant VSMCs hyperplasia and reduced restenosis.

PMID- 21850541
TI  - Expression pattern of ATM and cyclin D1 in ductal carcinoma, normal adjacent and
      normal breast tissues of Iranian breast cancer patients.
AB  - ATM protein kinase plays a critical role in maintaining genome integrity by
      activating a biochemical chain reaction that in turn leads to cell cycle
      checkpoint activation and repair of DNA damage. Cyclin D1 acts in regulating the
      G1 phase of the cell cycle. Experimental and clinical studies suggest them to be
      involved in transformation and tumour progression. To elucidate the role of ATM
      and cyclin D1 expression in sporadic breast cancer, we investigated the possible
      link between their RNA expression levels in ductal carcinoma and normal adjacent
      versus normal breast tissues measured by Taqman real-time PCR in 119 breast
      tissues. Results showed that cyclin D1 over-expressed in 51.4% of breast tumours,
      whereas ATM expression was down regulated in 55% of breast tumours compared to
      both normal adjacent and normal controls (P <= 0.01). Cyclin D1 expression in
      adjacent normal and normal tissues was not significantly differed, whereas ATM
      expression in normal adjacent was lower than normal control (P <= 0.01). Over
      expression of cyclin D1 correlated with ER(+) and/or PR(+)
      (oestrogen/progesterone receptor) status, whereas it mostly under-expressed in
      HER2(+) (human epidermal growth factor 2) tumours. ATM under-expression was more
      observed in triple-negative tumours (ER(-), PR(-) and HER2(-)). Our results
      indicated that reduced expression of the ATM and aberrant cyclin D1 expressions
      may contribute to the development and/or malignant progression of breast
      carcinomas also the latter could be involved in the regulation of hormone
      sensitivity associated with ER and PR.

PMID- 21850539
TI  - Membrane attack by complement: the assembly and biology of terminal complement
      complexes.
AB  - Complement system activation plays an important role in both innate and acquired
      immunity. Activation of the complement and the subsequent formation of C5b-9
      channels (the membrane attack complex) on the cell membranes lead to cell death.
      However, when the number of channels assembled on the surface of nucleated cells
      is limited, sublytic C5b-9 can induce cell cycle progression by activating signal
      transduction pathways and transcription factors and inhibiting apoptosis. This
      induction by C5b-9 is dependent upon the activation of the phosphatidylinositol 3
      kinase/Akt/FOXO1 and ERK1 pathways in a Gi protein-dependent manner. C5b-9
      induces sequential activation of CDK4 and CDK2, enabling the G1/S-phase
      transition and cellular proliferation. In addition, it induces RGC-32, a novel
      gene that plays a role in cell cycle activation by interacting with Akt and the
      cyclin B1-CDC2 complex. C5b-9 also inhibits apoptosis by inducing the
      phosphorylation of Bad and blocking the activation of FLIP, caspase-8, and Bid
      cleavage. Thus, sublytic C5b-9 plays an important role in cell activation,
      proliferation, and differentiation, thereby contributing to the maintenance of
      cell and tissue homeostasis.

PMID- 21850542
TI  - An essential role of PDCD4 in progression and malignant proliferation of
      gastrointestinal stromal tumors.
AB  - Programmed cell death 4 (PDCD4) is a tumor suppressor that can inhibit
      tumorigenesis by suppressing activator protein (AP)-1 activation and protein
      translation. Lost or decreased PDCD4 expression has been found in multiple types
      of human cancers, which was also associated with progression and metastasis of
      the tumors. However, the status and significance of PDCD4 in gastrointestinal
      stromal tumors have not been evaluated. In the present study, we examined the
      PDCD4 expression in a total of 63 gastrointestinal stromal tumor samples at both
      mRNA and protein levels by RT-PCR, western blot, and immunohistochemistry. We
      demonstrated that the expression of PDCD4 mRNA was diminished in 68% (17/25) of
      the tumor samples, and the level of PDCD4 protein appeared to be decreased in
      66.7% (42/63) of the samples, as compared to adjacent normal gastrointestinal
      tissues, which expressed high levels of PDCD4 mRNA and protein. In addition,
      altered expression of PDCD4 was associated with clinicopathological parameters
      including risk group, tumor size, and mitosis. Moreover, PDCD4 expression had a
      negative correlation with the Ki-67 labeling index (r = -0.6059, P < 0.0001). All
      these results suggest that downregulation of PDCD4 expression may have an
      essential role in the progression and malignant proliferation of human
      gastrointestinal stromal tumors.

PMID- 21850544
TI  - The effect of spatial competition between object-level representations of target
      and mask on object substitution masking.
AB  - One of the processes determining object substitution masking (OSM) is thought to
      be the spatial competition between independent object file representations of the
      target and mask (e.g., Kahan & Lichtman, 2006). In a series of experiments, we
      further examined how OSM is influenced by this spatial competition by
      manipulating the overlap between the surfaces created by the modal completion of
      the target (an outline square with a gap in one of its sides) and the mask (a
      four-dot mask). The results of these experiments demonstrate that increasing the
      spatial overlap between the surfaces of the target and mask increases OSM.
      Importantly, this effect is not caused by the mask interfering with the
      processing of the target features it overlaps. Overall, the data indicate,
      consistent with Kahan and Lichtman, that OSM can arise through competition
      between independent target and mask representations.

PMID- 21850545
TI  - A method to rapidly and accurately compare the relative efficacies of non
      invasive imaging reporter genes in a mouse model and its application to
      luciferase reporters.
AB  - PURPOSE: Our goal is to develop a simple, quantitative, robust method to compare
      the efficacy of imaging reporter genes in culture and in vivo. We describe an
      adenoviral vector-liver transduction procedure and compare the luciferase
      reporter efficacies. PROCEDURES: Alternative reporter genes are expressed in a
      common adenoviral vector. Vector amounts used in vivo are based on cell culture
      titrations, ensuring that the same transduction efficacy is used for each vector.
      After imaging, in vivo and in vitro values are normalized to hepatic vector
      transduction using quantitative real-time PCR. RESULTS: We assayed standard
      firefly luciferase (FLuc), enhanced firefly luciferase (EFLuc), luciferase 2
      (Luc2), humanized Renilla luciferase (hRLuc), Renilla luciferase 8.6-535
      (RLuc8.6), and a membrane-bound Gaussia luciferase variant (extGLuc) in cell
      culture and in vivo. We observed greater than 100-fold increase in bioluminescent
      signal for both EFLuc and Luc2 when compared to FLuc and greater than 106-fold
      increase for RLuc8.6 when compared to hRLuc. ExtGLuc was not detectable in liver.
      CONCLUSIONS: Our findings contrast, in some cases, with conclusions drawn in
      prior comparisons of these reporter genes and demonstrate the need for a
      standardized method to evaluate alternative reporter genes in vivo. Our procedure
      can be adapted for reporter genes that utilize alternative imaging modalities
      (fluorescence, bioluminescence, MRI, SPECT, PET).

PMID- 21850546
TI  - Fracture risk assessment without bone density measurement in routine clinical
      practice.
AB  - Fracture probability assessed without bone mineral density (BMD) could
      potentially be sufficient for clinical decision making in many individuals
      categorized as low or high fracture risk. For individuals falling in a moderate
      risk range, there is incremental value in using BMD in the probability
      calculation as this appropriately reclassifies risk in over one third of the
      individuals. INTRODUCTION: A new fracture risk assessment tool from the World
      Health Organization (FRAX) estimates 10-year major osteoporotic and hip fracture
      probabilities from multiple clinical risk factors with or without hip BMD. The
      objective of this study is to determine whether fracture probability derived
      without BMD can be used to identify individuals who would be designated for
      treatment. METHODS: A historical cohort of 36,730 women and 2,873 men aged 50
      years and older drawn from the Manitoba Bone Density Program database, which
      contains clinical BMD results for the Province of Manitoba, Canada, was included
      in the study. RESULTS: When 10-year probability for major osteoporotic fracture
      estimated without knowledge of BMD was high (>= 20%), the vast majority (92.8%)
      qualified for intervention under the National Osteoporosis Foundation (NOF)
      guidelines, whereas among those at low risk (<10%), the vast majority (80.5%) did
      not satisfy any NOF intervention criteria. The benefit of including BMD in the
      risk assessment was greatest among those initially at moderate risk (10-19%) when
      fracture probability was derived without BMD, but this represented only 29.4% of
      the cohort (9.3% of those aged < 65 years and 48.7% of those >= 65 years).
      CONCLUSIONS: Fracture probability derived without BMD is able to risk stratify
      women in terms of future fracture risk and could potentially be sufficient for
      clinical decision making in many of those designated at low or high fracture
      risk.

PMID- 21850547
TI  - Excess body fat is associated with higher risk of vertebral deformities in older
      women but not in men: a cross-sectional study.
AB  - Thinness is a risk factor for fractures, but the effect of obesity on fracture
      risk is less clear. We found an association between measures of obesity and
      prevalence and number of vertebral deformities in women but not in men, in a
      cross-sectional study of 1,011 participants aged 50-80 years. INTRODUCTION: Low
      body weight is well recognised as a risk factor for fractures, but the
      association between overweight and fracture risk is less well described. This
      cross-sectional study describes the association between measures of obesity and
      vertebral deformities in 1,011 male and female participants in the Tasmanian
      Older Adult Cohort study. METHODS: Vertebral deformities (anterior wedging) of T4
      L4 were determined by morphometric dual-emission X-ray absorptiometry. Body fat
      was assessed as weight, body mass index (BMI), waist-hip ratio (WHR), waist
      circumference and DXA measures of trunk fat (in percent) and total fat mass.
      RESULTS: The mean age of participants was 63 +/- 7 years, and mean BMI was 28 +/-
      5. Prevalent thoracic vertebral deformities were associated with increasing
      weight [standardised beta (Sbeta) 0.29, p = 0.003], BMI (Sbeta 0.33, p < 0.001),
      trunk fat (Sbeta 0.20, p = 0.03), waist circumference (Sbeta 0.19, p = 0.03) and
      fat mass (Sbeta 0.23, p = 0.03), but not the WHR in women, and only with
      decreasing total fat mass in men. In addition, the number of vertebral
      deformities increased as weight, BMI or fat mass increased in women (all p <
      0.05) but decreased with increasing total fat mass in men. Associations between
      fat mass and vertebral deformities were mainly linear, but there was some
      evidence of a threshold effect in women with a BMI >= 35. CONCLUSIONS: There is a
      deleterious association between increasing amounts of body fat in women but not
      in men and the prevalence and number of vertebral deformities, which may reflect
      loading of the thoracic spine.

PMID- 21850548
TI  - Relationship between serum RANKL and RANKL in bone.
AB  - It is now well accepted that the molecule receptor activator of NFkappaB ligand
      (RANKL) and osteoprotegerin play key roles in regulating physiological and
      pathological bone turnover. There are a large number of published reports of
      circulating RANKL levels in both health and pathology. However, interpretation of
      these data has been elusive, and the relationship between circulating RANKL and
      RANKL levels in bone is still not clear. This review explores this subject,
      documenting the possible origins of circulating RANKL and suggesting additional
      information that is required before serum RANKL levels can provide useful
      diagnostic or research information.

PMID- 21850550
TI  - Characterization of a Fricke dosimeter at high energy photon and electron beams
      used in radiotherapy.
AB  - The dosimetric features of the Fricke dosimeter in clinical linear accelerator
      beams are considered. Experimental data were obtained using various nominal
      energies 6 and 18 MV, 12 and 15 MeV, including the (60)Co gamma-ray beam. The
      calibration of the dosimeters was performed using the ionization chamber as a
      reference dosimeter. Some general characteristics of Fricke dosimeter such as
      energy dependence, optical density (OD)-dose relationship, reproducibility,
      accuracy, dose rate dependence were analyzed. The Fricke solution shows linearity
      in OD-dose relationship, energy independence and a good reproducibility over the
      energy range investigated. The Fricke dosimeter was found to be suitable for
      carrying out absorbed dose to water measurements in the calibration of high
      energy electron and photon beams.

PMID- 21850549
TI  - Overweight in childhood and bone density and size in adulthood.
AB  - We evaluated the adult bone structural traits in relation to childhood overweight
      in 832 men and women. Childhood overweight was associated with larger cross
      sections at long bones in both sexes. Excess weight in childhood may also lead to
      higher trabecular density in females and somewhat lower cortical density in men.
      INTRODUCTION: Excess body weight in childhood may impose more loading on growing
      skeleton and thus lead to more robust structure in adulthood. METHODS: This
      prospective cohort study evaluated the adult bone structural traits in relation
      to childhood overweight in a subgroup of 456 women and 376 men from the
      population-based cohort of Cardiovascular Risks in Young Finns Study. Between
      group differences were evaluated with analysis of covariance. RESULTS: According
      to established body mass index (BMI) criterion at the age of 12 years, 31 women
      and 34 men were classified overweight in childhood. At the mean age (SD) of 36.1
      (2.7) years, total cross-sectional (ToA) and cortical area (CoA) at the distal
      and shaft sites and cortical (shaft CoD) and trabecular (distal TrD) bone density
      of the nonweight-bearing radius and weight-bearing tibia were evaluated with
      pQCT. Despite being taller in adolescence, the adult body height of overweight
      children was similar. In both sexes, childhood overweight was consistently
      associated with 5-10% larger ToA at all bone sites measured in adulthood. CoA did
      not show such a consistent pattern. Women, who were overweight in childhood, had
      ~5% denser TrD with no difference in CoD. In contrast, TrD in men who were
      overweight in childhood was not different but their CoD was ~1% lower.
      CONCLUSIONS: Childhood overweight was consistently associated with larger long
      bone cross-sections in both sexes. Excess weight in childhood may also lead to
      higher trabecular density in women and somewhat lower cortical density in men.
      Specific mechanisms underlying these associations are not known.

PMID- 21850551
TI  - Vertical integration and optimal reimbursement policy.
AB  - Health care providers may vertically integrate not only to facilitate
      coordination of care, but also for strategic reasons that may not be in patients'
      best interests. Optimal Medicare reimbursement policy depends upon the extent to
      which each of these explanations is correct. To investigate, we compare the
      consequences of the 1997 adoption of prospective payment for skilled nursing
      facilities (SNF PPS) in geographic areas with high versus low levels of
      hospital/SNF integration. We find that SNF PPS decreased spending more in high
      integration areas, with no measurable consequences for patient health outcomes.
      Our findings suggest that integrated providers should face higher-powered
      reimbursement incentives, i.e., less cost-sharing. More generally, we conclude
      that purchasers of health services (and other services subject to agency
      problems) should consider the organizational form of their suppliers when
      choosing a reimbursement mechanism.

PMID- 21850552
TI  - Caeco-colic intussusception in an adult: a rare case report.
AB  - Intussusception is common in children but rare in adults. Caeco-colic
      intussusception is an uncommon cause of intestinal obstruction in adults. Very
      limited information is available about the role of colonoscopy in diagnosis of
      intussusception in the literature. We present a case of caeco-colic
      intussusception in a 50-year-old male who presented with the complaints of pain
      in abdomen and a lump in the right hypochondrium. Colonoscopy and contrast
      studies revealed the diagnosis of intussusception. Abdominal computed tomography
      (CT scan) is considered as the most sensitive investigation to diagnose
      intussusception at present, whereas colonoscopy is sparingly used to diagnose
      intussusception. In this patient, colonoscopy not only established the diagnosis
      and malignant nature of the lead point, but also guided the definitive extent of
      surgical resection. CT scan offers a presumptive diagnosis as compared to the
      definitive diagnosis of intussusception by colonoscopy. In adult intussusception,
      colonoscopy can be considered as a complimentary investigation to other
      diagnostic modalities. Hence regular use of colonoscopy in adult intussusception
      should be encouraged where presentation is either subacute or chronic.

PMID- 21850553
TI  - Prospective randomized controlled study using polyethylene mesh for inguinal
      hernia meshplasty as a safe and cost-effective alternative to polypropylene mesh.
AB  - Most patients who come to a general hospital in a developing country are poor.
      The most important prohibiting factor for use of polypropylene mesh in hernia
      repair is its exorbitant cost. Hence, research workers have been on the lookout
      for an equally effective but economically affordable mesh. Worldwide, surgical
      repair of inguinal hernia is the most common general surgery procedure performed
      at the present. Lifetime risk of groin hernia is 15% in males and 5% in females.
      Most of the patients who visit a general hospital are from either lower middle
      class or poor socioeconomic strata. The most important prohibiting factor for use
      of polypropylene mesh in hernia repair for the common man is its exorbitant cost.
      The aim of this study is to document the feasibility, safety and cost
      effectiveness of the use of polyethylene mesh. A single blind, prospective,
      randomized controlled study, comparing 35 patients of two groups was conducted in
      a tertiary teaching hospital over a period of 5 years. The patients in both
      groups underwent inguinal hernioplasty, and were administered similar antibiotics
      and analgesics. The postoperative course with regard to pain, seroma formation,
      infection, hospital stay, recurrence and scar quality was evaluated and compared.
      Statistical analysis was performed with Chi square test. The properties of both
      meshes were the same with respect to ease of handling, pain score, seroma
      formation, infection rate, resumption of daily activities, scar quality and mesh
      rejection. Recurrence rate was zero for both groups. Polyethylene mesh was 2,808
      times cheaper than the commercially available polypropylene mesh. This study
      proved the safety, simplicity, efficacy and cost-effectiveness of polyethylene
      mesh for inguinal hernia meshplasty, insuring economical, accessible health care
      for the financially weak section of the population.

PMID- 21850554
TI  - Biliodigestive anastomosis with circular mechanical device after
      pancreatoduodenectomy: our experience.
AB  - The authors describe the technique to perform a mechanical biliodigestive
      anastomosis after pancreatoduodenectomy that could be able to reduce the time of
      surgical intervention and the major systemic postoperative complication
      especially in elderly patients. Pancreaticoduodenectomy (PD) is considered to be
      the most effective procedure for the treatment of tumors of the pancreatic head
      and periampullary tumors. Postoperative morbidity remains high, reaching 40-50%
      in some series. Leakage and stricture of hepaticojejunal anastomosis have a
      special significance and occur in 2.5-5% of cases. The usefulness of mechanical
      staplers is well established in gastric and colorectal surgery, but their use in
      creating biliodigestive anastomosis is still a very controversial application. In
      the last 2 years (Nov 2008-Nov 2010), seven patients who underwent PD and
      presented at the time of operation, a main bile duct (MBD) greater of 20 mm,
      received a mechanical biliodigestive anastomosis with surgical stapler. All the
      patients were postoperatively controlled with an ultrasonography at 3 and 6
      months, and a cholangio MRI at 1 year from operation. The follow up of the seven
      patients ranged from 3 to 18 months. Six patients are still alive and free of
      oncologic disease. One patient presented a single episode of cholangitis with a
      significant reduction of caliber of the biliodigestive anastomosis. The remaining
      five patients showed a good caliber of hepaticojejunal anastomosis. The authors
      suggest this procedure as a safe, feasible, more rapid and easier technique than
      traditional suture for bilioenteric anastomosis, when a suitable caliber of MBD
      allows to perform it.

PMID- 21850555
TI  - Social conditions and urban health inequities: realities, challenges and
      opportunities to transform the urban landscape through research and action.
AB  - The process of urbanization entails social improvements with the consequential
      better quality-of-life for urban residents. However, in many low-income and some
      middle-income countries, urbanization conveys inequality and exclusion, creating
      cities and dwellings characterized by poverty, overcrowded conditions, poor
      housing, severe pollution, and absence of basic services such as water and
      sanitation. Slums in large cities often have an absence of schools,
      transportation, health centers, recreational facilities, and other such
      amenities. Additionally, the persistence of certain conditions, such as poverty,
      ethnic heterogeneity, and high population turnover, contributes to a lowered
      ability of individuals and communities to control crime, vandalism, and violence.
      The social vulnerability in health is not a "natural" or predefined condition but
      occurs because of the unequal social context that surrounds the daily life of the
      disadvantaged, and often, socially excluded groups. Social exclusion of
      individuals and groups is a major threat to development, whether to the community
      social cohesion and economic prosperity or to the individual self-realization
      through lack of recognition and acceptance, powerlessness, economic
      vulnerability, ill health, diminished life experiences, and limited life
      prospects. In contrast, social inclusion is seen to be vital to the material,
      psychosocial, and political aspects of empowerment that underpin social well
      being and equitable health. Successful experiences of cooperation and networking
      between slum-based organizations, grassroots groups, local and international
      NGOs, and city government are important mechanisms that can be replicated in
      urban settings of different low- and middle-income countries. With increasing
      urbanization, it is imperative to design health programs for the urban poor that
      take full advantage of the social resources and resourcefulness of their own
      communities.

PMID- 21850556
TI  - Branchial cleft cyst with xanthogranulomatous inflammation.
AB  - Xanthogranulomatous inflammation (XGI) is a special type of inflammation
      presenting as mass lesions and mimicking malignant tumors. It is rarely described
      in the head and neck region, and to the best of our knowledge, there are no cases
      associated with branchial cleft cyst. A 39-year-old woman with an infiltrative
      cystic neck mass that radiologically mimicks a malignant tumor is herein
      presented. The histopathologic diagnosis was a branchial cleft cyst with XGI. XGI
      may be associated wih branchial cleft cysts. Patients may present with radiologic
      findings mimicking an invasive malignant tumor, and should be taken into account
      during the differential diagnosis with cystic squamous cell carcinoma.

PMID- 21850557
TI  - A clinical commentary on the article "N-acetylglucosamine conjugated to
      nanoparticles enhances myocyte uptake and improves delivery of a small molecule
      p38 inhibitor for post-infarct healing" : N-acetylglucosamine conjugated
      nanoparticles: translational opportunities and barriers.
AB  - Targeting drugs and nanoparticles to cardiomyocytes has been an elusive
      challenge. Cardiomyocytes are inherently non-phagocytic and their environment is
      subjected to contractile forces which tend to expel injected and catheter
      delivered drugs. In this issue, a novel-targeting strategy, N-acetyl-glucosamine
      (GlcNAc) coating, is shown to enhance cardiomyocyte nanoparticle uptake both in
      vitro and in vivo. Many effective and proven therapies for myocardial infarction
      are in clinical use thus raising the bar for the translation of new technologies.
      Nevertheless, GlcNAc targeting represents a promising approach for improved
      targeting of drug therapies to cardiomyocytes.

PMID- 21850558
TI  - A clinical commentary on the article "EMT-inducing biomaterials for heart valve
      engineering: taking cues from developmental biology" : clinical utilization of
      tissue-engineered heart valves--meeting today's standard.

PMID- 21850560
TI  - The T. Mort. Chaplaincy at ground zero: presence and privilege on holy ground.
AB  - Drawing on interviews with the chaplains and archival material from Disaster
      Chaplaincy Services--NY, this article discusses the formation of the chaplaincy
      at the Temporary Mortuary at Ground Zero after the terrorist attacks on September
      11, 2001. It describes the initial chaplaincy response in New York by local
      clergy and the SAIR team of the American Red Cross. The first 6 weeks of
      chaplaincy at Ground Zero are explored highlighting the significant contributions
      of the Archdiocese of New York and Episcopal Diocese of New York out of St.
      Paul's Chapel. The mission and impact of the Temporary Mortuary chaplains'
      ministry of presence and blessing is discussed with some final reflections for
      the future of Disaster Chaplaincy.

PMID- 21850559
TI  - Serological survey of Paracoccidioidomycosis in sheep.
AB  - The objective of this study was to evaluate the prevalence of antibodies against
      Paracoccidioides brasiliensis in sheep from Guarapuava, Parana State, Brazil. The
      seroepidemiological study was carried out in 262 sheep. The samples were analyzed
      by ELISA and immunodiffusion test using P. brasiliensis gp43 and exoantigen as
      antigens, respectively. Initially, two sheep were immunized with P. brasiliensis
      to evaluate whether contact with the fungal cells could induce a humoral immune
      response against gp43 and exoantigen from P. brasiliensis. Both animals produced
      antibodies against gp43 and exoantigen, the main antigens used for diagnosis and
      seroepidemiology of paracoccidioidomycosis. A reactivity of 37% was observed to
      the P. brasiliensis gp43 antigen by ELISA although no reactivity had been
      observed by the immunodiffusion test. Sheep under extensive grazing system showed
      higher frequency of positivity to P. brasiliensis (P <= 0.05) than those under
      intensive and semi-intensive systems. These data suggest that sheep may be a
      useful epidemiological marker of P. brasiliensis presence in the environment and
      reinforce that contact with soil is an important risk factor for infection.

PMID- 21850561
TI  - Global IRS-1 phosphorylation analysis in insulin resistance.
AB  - AIMS/HYPOTHESIS: IRS-1 serine phosphorylation is often elevated in insulin
      resistance models, but confirmation in vivo in humans is lacking. We therefore
      analysed IRS-1 phosphorylation in human muscle in vivo. METHODS: We used HPLC
      electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and
      after insulin infusion in vastus lateralis muscle from lean healthy, obese non
      diabetic and type 2 diabetic volunteers. RESULTS: Basal Ser323 phosphorylation
      was increased in type 2 diabetic patients (2.1 +/- 0.43, p <= 0.05, fold change
      vs lean controls). Thr495 phosphorylation was decreased in type 2 diabetic
      patients (p <= 0.05). Insulin increased IRS-1 phosphorylation at Ser527 (1.4 +/-
      0.17, p <= 0.01, fold change, 60 min after insulin infusion vs basal) and Ser531
      (1.3 +/- 0.16, p <= 0.01, fold change, 60 min after insulin infusion vs basal) in
      the lean controls and suppressed phosphorylation at Ser348 (0.56 +/- 0.11, p <=
      0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64 +/-
      0.16, p <= 0.05, fold change, 60 min after insulin infusion vs basal), Ser1100
      (0.77 +/- 0.22, p <= 0.05, fold change, 240 min after insulin infusion vs basal)
      and Ser1142 (1.3 +/- 0.2, p <= 0.05, fold change, 60 min after insulin infusion
      vs basal). CONCLUSIONS/INTERPRETATION: We conclude that, unlike some aspects of
      insulin signalling, the ability of insulin to increase or suppress certain IRS-1
      phosphorylation sites is intact in insulin resistance. However, some IRS-1
      phosphorylation sites do not respond to insulin, whereas other Ser/Thr
      phosphorylation sites are either increased or decreased in insulin resistance.

PMID- 21850562
TI  - Evaluation and imaging of an untreated grade III hamstring tear: a case report.
AB  - BACKGROUND: Muscle strains are one of the most common complaints treated by
      physicians. High-force lengthening contractions can produce very high forces
      resulting in pain and tissue damage; such strains are the most common cause of
      muscle injuries. The hamstring muscles are particularly susceptible as they cross
      two joints and regularly perform lengthening contractions during running. We
      describe a patient with return to full function after a large hamstring tear.
      CASE DESCRIPTION: We report the case of a 26-year-old man who presented 1 year
      after a noncontact, left-sided proximal hamstring tear incurred while sprinting.
      He received no medical treatment or formal rehabilitation. He was able to return
      to all sports and activities 1 to 2 months after injury, but noted a persistent
      deformity of the proximal thigh, which led him to seek evaluation. Physical
      examination, MRI functional tests, and specific muscle tests 1 year after his
      injury documented a major hamstring tear at the musculotendinous junction with
      muscle retraction, but no avulsion of the proximal tendon attachment. LITERATURE
      REVIEW: Surgery often is recommended for major proximal hamstring tendon tears,
      especially when more than one tendon of origin is ruptured from the ischial
      tuberosity. Myotendinous tears are treated nonoperatively, but may be associated
      with decreased strength, prolonged recovery, and recurrence. PURPOSE AND CLINICAL
      RELEVANCE: We describe the case of a young man who sustained a hamstring tear,
      with retraction, at the proximal myotendinous junction, where the biceps femoris
      and semitendinosus arise from the conjoint tendon. He achieved full functional
      recovery without medical attention, but had a persistent cosmetic deformity and
      slight hamstring tightness. This case suggests a benign natural history for this
      injury and the appropriateness of noninvasive treatment.

PMID- 21850563
TI  - Spontaneous subarachnoid hemorrhage and glucose management.
AB  - Although metabolic abnormalities have been linked with poor outcome after
      subarachnoid hemorrhage, there are limited data addressing the impact of glycemic
      control or benefits of glucose management after aneurysmal subarachnoid
      hemorrhage. A systematic literature search was conducted of English-language
      articles describing original research on glycemic control in patients with
      subarachnoid hemorrhage. Case reports and case series were excluded. A total of
      22 publications were selected for this review. Among the 17 studies investigating
      glucose as an outcome predictor, glucose levels during hospitalization were more
      likely to predict outcome than admission glucose. In general, hyperglycemia was
      linked to worse outcome. While insulin therapy in subarachnoid hemorrhage
      patients was shown to effectively control plasma glucose levels, plasma glucose
      control was not necessarily reflective of cerebral glucose such that very tight
      glucose control may lead to neuroglycopenia. Furthermore, tight glycemic control
      was associated with an increased risk for hypoglycemia which was linked to worse
      outcome.

PMID- 21850564
TI  - Preoperative FDG-PET predicts recurrence patterns in hepatocellular carcinoma.
AB  - PURPOSE: We investigated the usefulness of preoperative fluorine-18
      fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool for
      predicting recurrence patterns to select patients for liver resection as an
      initial surgical strategy for hepatocellular carcinoma. METHODS: Sixty-three
      consecutive hepatocellular carcinoma patients undergoing FDG-PET were enrolled.
      They were classified according to the initial recurrence patterns (beyond the
      Milan criteria [MC], within the MC, and no recurrence) and the time intervals
      before initial postoperative recurrence (within 1 year, after 1 year or later,
      and no recurrence). The tumor-to-nontumor ratio (TNR) obtained by FDG-PET and
      survival rates were compared among the groups. RESULTS: TNR in the recurrence
      within the MC group (1.9 +/- 1.6) and no recurrence group (1.3 +/- 1.5) was
      significantly lower than that in the beyond the MC group (2.9 +/- 2.6). TNR was
      an independent predictive factor of recurrence patterns in multivariate analysis.
      TNR in the groups with recurrence after 1 year or later (1.6 +/- 0.8) and no
      recurrence (1.3 +/- 0.5) were significantly lower than that in the within 1-year
      group (3.1 +/- 2.7). TNR was an independent predictive factor of the interval
      before initial recurrence by multivariate analysis. CONCLUSIONS: Preoperative FDG
      PET predicts hepatocellular carcinoma recurrences within the MC or no recurrence
      and recurrences after 1 year or later. FDG-PET may be useful for selecting
      appropriate patients for liver resection as an initial surgical strategy.

PMID- 21850565
TI  - Uterine artery embolization to treat uterine adenomyosis with or without uterine
      leiomyomata: results of symptom control and health-related quality of life 40
      months after treatment.
AB  - PURPOSE: To evaluate the clinical outcome for uterine adenomyosis with or without
      uterine leiomyomata 40 months after uterine artery embolization (UAE). METHODS:
      Forty women aged 39-56 years (median 46 years) with symptomatic uterine
      adenomyosis and magnetic resonance imaging findings of uterine adenomyosis with
      or without combined uterine leiomyomata underwent UAE. Self-perceived changes in
      clinical symptoms were assessed, and residual symptom severity and health-related
      quality of life (HRQOL) after UAE were evaluated. Clinical failure was defined as
      no symptomatic improvement or second invasive therapy after UAE. Results were
      stratified by the extent of uterine adenomyosis at baseline magnetic resonance
      imaging. RESULTS: Patients were followed for a median of 40 months (range 5-102
      months). UAE led to symptomatic control after UAE in 29 (72.5%) of 40 patients
      while 11 women underwent hysterectomy (n=10) or dilatation and curettage (n=1)
      for therapy failure. No significant difference between women with pure uterine
      adenoymosis and women with uterine adenomyosis combined with uterine leiomyomata
      was observed. Best results were shown for UAE in uterine adenomyosis with uterine
      leiomyomata predominance as opposed to predominant uterine adenomyosis with minor
      fibroid disease (clinical failure 0% vs. 31.5%, P=0.058). Throughout the study
      group, HRQOL score values increased and symptom severity scores decreased after
      UAE. Least improvement was noted for women with pure adenomyosis. CONCLUSIONS:
      UAE is clinically effective in the long term in most women with uterine
      adenomyosis. Symptomatic control and HRQOL were highest in patients with combined
      disease of uterine adenomyosis but leiomyomata predominance.

PMID- 21850566
TI  - Just the facts: historical corrective to Malon (2011).

PMID- 21850567
TI  - Misdiagnoses of pedohebephilia using victim count: a reply to Wollert and Cramer
      (2011).

PMID- 21850568
TI  - A comparative theoretical study of the catalytic activities of Au2(-) and AuAg(-)
      dimers for CO oxidation.
AB  - The detailed mechanisms of catalytic CO oxidation over Au(2)(-) and AuAg(-)
      dimers, which represent the simplest models for monometal Au and bimetallic Au-Ag
      nanoparticles, have been studied by performing density functional theory
      calculations. It is found that both Au(2)(-) and AuAg(-) dimers catalyze the
      reaction according to the similar mono-center Eley-Rideal mechanism. The
      catalytic reaction is of the multi-channel and multi-step characteristic, which
      can proceed along four possible pathways via two or three elementary steps. In
      AuAg(-), the Au site is more active than the Ag site, and the calculated energy
      barrier values for the rate-determining step of the Au-site catalytic reaction
      are remarkably smaller than those for both the Ag-site catalytic reaction and the
      Au(2)(-) catalytic reaction. The better catalytic activity of bimetallic AuAg(-)
      dimer is attributed to the synergistic effect between Au and Ag atom. The present
      results provide valuable information for understanding the higher catalytic
      activity of Au-Ag nanoparticles and nanoalloys for low-temperature CO oxidation
      than either pure metallic catalyst.

PMID- 21850569
TI  - Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited
      AChE: a computational study.
AB  - Oximate anions are used as potential reactivating agents for OP-inhibited AChE
      because of they possess enhanced nucleophilic reactivity due to the alpha-effect.
      We have demonstrated the process of reactivating the VX-AChE adduct with
      formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6
      311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine
      anion is more efficient than the formoximate anion at reactivating VX-inhibited
      AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step
      process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems
      to be a two-step process. The rate-determining step in the process is the initial
      attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps
      are exergonic in nature. The potential energy surface (PES) for the reaction of
      the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process
      is facilitated by the lower free energy of activation (by a factor of 1.7 kcal
      mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of
      theory. The higher free energy of activation for the reverse reactivation
      reaction between hydroxylamine anion and the VX-serine adduct further suggests
      that the hydroxylamine anion is a very good antidote agent for the reactivation
      process. The activation barriers calculated in solvent using the polarizable
      continuum model (PCM) for the reactivation of the VX-AChE adduct with
      hydroxylamine anion were also found to be low. The calculated results suggest
      that V-series compounds can be more toxic than G-series compounds, which is in
      accord with earlier experimental observations.

PMID- 21850570
TI  - Insights into the structural function of the complex of HIV-1 protease with TMC
      126: molecular dynamics simulations and free-energy calculations.
AB  - The binding properties of the protein-inhibitor complex of human immunodeficiency
      virus type 1 (HIV-1) protease with the inhibitor TMC-126 are investigated by
      combining computational alanine scanning (CAS) mutagenesis with binding free
      energy decomposition (BFED). The calculated results demonstrate that the flap
      region (residues 38-58) and the active site region (residues 23-32) in HIV-1
      protease contribute 63.72% of the protease to the binding of the inhibitor. In
      particular, the mechanisms for the interactions of key residues of these species
      are fully explored and analyzed. Interestingly, the regression analyses show that
      both CAS and BFED based on the generalized Born model yield similar results, with
      a correlation coefficient of 0.94. However, compared to CAS, BFED is faster and
      can decompose the per-residue binding free-energy contributions into backbone and
      side-chain contributions. The results obtained in this study are useful for
      studying the binding mechanism between receptor and ligand and for designing
      potent inhibitors that can combat diseases.

PMID- 21850571
TI  - In silico quest for putative drug targets in Helicobacter pylori HPAG1: molecular
      modeling of candidate enzymes from lipopolysaccharide biosynthesis pathway.
AB  - Aimed at identification and structural characterization of novel putative
      therapeutic targets in H. pylori, the etiological agent of numerous
      gastrointestinal diseases including peptic ulcer and gastric cancer, the present
      study comprised of three phases. First, through subtractive analysis of metabolic
      pathways of Helicobacter pylori HPAG1 and human, as documented in the KEGG
      database, 11 pathogen-specific pathways were identified. Next, all proteins
      involved in these pathogen-specific pathways were scrutinized in search of
      promising targets and the study yielded 25 candidate target proteins that are
      likely to be essential for the pathogen viability, but have no homolog in human.
      The lipopolysaccharide (LPS) biosynthesis pathway was found to be the largest
      contributor (nine proteins) to this list of candidate proteins. Considering the
      importance of LPS in H. pylori virulence, 3D structural models of three predicted
      target enzymes of this pathway, namely 2-dehydro-3-deoxy-phosphooctonate
      aldolase, UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase and
      Phosphoheptose isomerase, were then built up using the homology modeling
      approaches. Binding site analysis and docking of the known biological substrate
      PEP to 2-dehydro-3-deoxyphosphooctonate aldolase revealed the potential binding
      pocket present in the single monomeric form of the enzyme and identified 11 amino
      acid residues that might play the key roles in this protein-ligand interaction.

PMID- 21850572
TI  - Development of multiple QSAR models for consensus predictions and unified
      mechanistic interpretations of the free-radical scavenging activities of chromone
      derivatives.
AB  - Antioxidants are important defenders of the human body against nocive free
      radicals, which are the causative agents of most life-threatening diseases. The
      immense biomedicinal utility of antioxidants necessitates the development and
      design of new synthetic antioxidant molecules. The present report deals with the
      modeling of a series of chromone derivatives, which was done to provide detailed
      insight into the main structural fragments that impart antioxidant activity to
      these molecules. Four different quantitative structure-property relationship
      (QSAR) techniques, namely 3D pharmacophore mapping, comparative molecular
      similarity indices analysis (CoMSIA 3D-QSAR), hologram QSAR (HQSAR), and group
      based QSAR (G-QSAR) techniques, were employed to obtain statistically significant
      models with encouraging external predictive potentials. Moreover, the visual
      contribution maps obtained for the different models signify the importance of
      different structural features in specific regions of the chromone nucleus.
      Additionally, the G-QSAR models determine the composite influence of pairs of
      substituent fragments on the overall antioxidant activity profiles of the
      molecules. Multiple models with different strategies for assessing structure
      activity relationships were applied to reach a unified conclusion regarding the
      antioxidant mechanism and to provide consensus predictions, which are more
      reliable than values derived from a single model. The structural information
      obtained from the various QSAR models developed in the present work can thus be
      effectively utilized to design and predict the activities of new molecules
      belonging to the class of chromone derivatives.

PMID- 21850573
TI  - Inhibition of ubiquitin proteasome function suppresses proliferation of pulmonary
      artery smooth muscle cells.
AB  - Inhibition of proteasome function has been shown to suppress several types of
      cells proliferation; this study investigates whether this also occurs in
      pulmonary artery smooth muscle cells (PASMCs) and its potential mechanisms.
      Serotonin induced 4.27-fold increase in DNA synthesis in PASMCs, and this effect
      was dose-dependently blocked by prior incubation of cells with MG132, a specific
      proteasome inhibitor. Inhibition of proteasome function did not modulate
      serotonin-triggered pro-proliferation signaling pathways, such as extracellular
      signal-regulated mitogen-activated protein kinase (ERK1/2 MAPK) and Ras homolog
      gene family member A (RhoA). Further study indicated that treatment of PASMCs
      with serotonin reduced p21(WAF1) protein level but not its transcription; this
      was reversed by inhibiting ERK1/2 MAPK or RhoA cascade equally. In addition,
      MG132 increased the protein level of p21(WAF1) in a dose-dependent manner in the
      presence of serotonin, 10 MUM MG132 led to a 4.2-fold increase in p21(WAF1)
      protein level, and this effect was not mediated by increasing p21(WAF1) mRNA
      level. More importantly, cell lacking p21(WAF1) by siRNA transfection abolished
      the inhibitive effect of MG132 on cells proliferation. Our study suggests that
      accumulation of p21(WAF1) protein level caused by proteasome inhibition
      particularly mediated its inhibitive effect on PASMCs proliferation, and
      inhibition of proteasome function might have potential value in the treatment of
      pulmonary hypertension.

PMID- 21850574
TI  - Pressor response to oral tyramine during co-administration with safinamide in
      healthy volunteers.
AB  - The aim of this study was to evaluate the pressor response to oral tyramine
      during repeated administration of oral safinamide in healthy volunteers. Twelve
      females and eight males aged 52.7 +/- 4.9 years entered the study. An oral
      tyramine screening test was conducted to select subjects sensitive to the
      tyramine pressor effect on systolic blood pressure (SBP) in the dose range of 200
      400 mg. Safinamide 300 mg was then administered once daily under fasting
      conditions. Starting on day 5 (safinamide pharmacokinetic steady state), single
      ascending doses of tyramine were co-administered daily: 50, 100 and 200 mg were
      administered on days 5, 6 and 7, respectively. Vital parameters were monitored by
      telemetry. No SBP increase >=30 mmHg over baseline was observed when tyramine was
      co-administered with safinamide. Less than one third of the 400 mg responders
      reported SBP increases between 22 and 27 mmHg, which were below the threshold of
      30 mmHg over baseline. SBP increases, as well as time interval to pressor
      response measured after co-treatment with safinamide and tyramine 200 mg, were
      not significantly different from those measured after administration of oral
      tyramine 200 mg alone. Safinamide 300 mg, administered o.d. under fasting
      conditions, does not change the tyramine pressor response as evaluated at steady
      state after 6-7 days of treatment as compared with the effect of tyramine
      administered alone. Safinamide, which inhibits monoamine oxidase (MAO)-B, does
      not affect oral tyramine metabolism mediated mostly by the intestinal MAO-A.

PMID- 21850575
TI  - Genetic analysis of lung function in inbred mice suggests vitamin D receptor as a
      candidate gene.
AB  - Vitamin D receptor (VDR) polymorphisms are associated with an increased asthma
      incidence in human populations; however, observations in Vdr knockout mice are
      unclear. The aim of our study was to determine the influence of the genetic
      variation in Vdr among inbred strains on lung resistance (i.e., dynamic and
      airway resistance). In an intercross between the strains C57BL/6J (B6) and KK/HlJ
      (KK), we identified that a significant QTL for dynamic resistance on Chr X was
      interacting with a QTL on Chr 15. The Chr 15 QTL peak was located in close
      proximity to the Vdr locus. We further examined if phenotypes of several inbred
      strains with varying Vdr genotypes differed. Strains with a B6-like genotype on
      the Vdr locus had significantly lower airway resistance than strains with a KK
      like genotype. Vdr knockout mice were examined for dynamic resistance and showed
      significantly higher resistance than mice with one (i.e., heterozygous) or both
      copies (i.e., wild-type) of the Vdr. In comparison to B6, the strain A/J is more
      resistant but carries the same genotype at the Vdr locus. Dietary vitamin D
      manipulation in the strain A/J did not rescue the high airway resistance
      phenotype. Finally, we observed that serum vitamin D does not correlate
      significantly with lung resistance parameters in a survey of 18 strains.
      Conclusively, Vdr contributes to the phenotypic variation of lung resistance in
      inbred mice but other molecules in the Vdr pathway and extended network [i.e.,
      Chr X gene(s)] may contribute as well.

PMID- 21850576
TI  - Vascular calcification estimated by aortic calcification area index is a
      significant predictive parameter of cardiovascular mortality in hemodialysis
      patients.
AB  - BACKGROUND: Vascular calcification is a feature of arteriosclerosis. In
      hemodialysis (HD) patients, vascular calcification progresses rapidly. This study
      used the aortic calcification area index (ACAI), an index of vascular
      calcification, to evaluate vascular calcification factors in HD patients, to
      investigate correlations between ACAI and long-term prognosis and to assess
      correlations between various factors and long-term prognosis. METHODS: Subjects
      comprised 137 patients on maintenance HD. ACAI was measured as an index of
      vascular calcification as measured by abdominal plain computed tomography. The
      patients were divided into a high ACAI (H) group and a low ACAI (L) group
      according to whether the ACAI was below or above the mean value (21.4%) of ACAI,
      and long-term all-cause death and cardiovascular death rates were compared
      between groups. Risk factors for all-cause death and cardiovascular death were
      examined by Cox hazard analysis. RESULTS: During follow-up (mean follow-up period
      95.3 +/- 50.3 months), 76 patients died, including 46 cardiovascular deaths.
      Deaths included 51 of 70 patients (67.1%) in Group H and 25 of 67 patients
      (37.3%) in Group L. Cardiovascular death rates were 51.4 and 14.9%, respectively.
      On Kaplan-Meier analysis, the number of all-cause deaths was significantly higher
      in Group H (P < 0.001, log-rank test). Similarly, the number of cardiovascular
      deaths was significantly higher in Group H. Multivariate Cox proportional hazards
      analysis showed that ACAI (%) was a significant prognostic indicator for
      cardiovascular death (hazard ratio 1.03; 95% confidence interval 1.00-1.06, P =
      0.03). CONCLUSION: High ACAI was clearly correlated with mortality rate in HD
      patients, particularly cardiovascular mortality rate. ACAI was a useful long-term
      prognostic indicator in HD patients.

PMID- 21850577
TI  - Experimental design to optimize an Haemophilus influenzae type b conjugate
      vaccine made with hydrazide-derivatized tetanus toxoid.
AB  - The introduction of type b Haemophilus influenzae conjugate vaccines into routine
      vaccination schedules has significantly reduced the burden of this disease;
      however, widespread use in developing countries is constrained by vaccine costs,
      and there is a need for a simple and high-yielding manufacturing process. The
      vaccine is composed of purified capsular polysaccharide conjugated to an
      immunogenic carrier protein. To improve the yield and rate of the reductive
      amination conjugation reaction used to make this vaccine, some of the carboxyl
      groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which
      are more reactive than the epsilon -amine of lysine. Other reaction parameters,
      including the ratio of the reactants, the size of the polysaccharide, the
      temperature and the salt concentration, were also investigated. Experimental
      design was used to minimize the number of experiments required to optimize all
      these parameters to obtain conjugate in high yield with target characteristics.
      It was found that increasing the reactant ratio and decreasing the size of the
      polysaccharide increased the polysaccharide:protein mass ratio in the product.
      Temperature and salt concentration did not improve this ratio. These results are
      consistent with a diffusion controlled rate limiting step in the conjugation
      reaction. Excessive modification of tetanus toxoid with hydrazide was correlated
      with reduced yield and lower free polysaccharide. This was attributed to a
      greater tendency for precipitation, possibly due to changes in the isoelectric
      point. Experimental design and multiple regression helped identify key parameters
      to control and thereby optimize this conjugation reaction.

PMID- 21850579
TI  - Treatment for pulmonary hypertension including lung transplantation.
AB  - Pulmonary hypertension (PH) is a progressive disease characterized by sustained
      elevation in pulmonary arterial pressure and increased pulmonary vascular
      resistance, leading to right-sided ventricular failure. The untreated median
      survival period is 2-3 years from the time of diagnosis, with the cause of death
      usually being right-sided ventricular failure. However, outcomes have
      dramatically changed in recent years because of great advances in medical
      management of PH, including early diagnosis and new drugs such as prostaglandins,
      endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Long
      term continuous intravenous prostacyclin therapy has shown excellent results in
      patients with PH. More recently, a molecular-targeted agent, imatinib mesylate,
      that acts by specifically inhibiting a certain enzyme that is characteristic of a
      particular cancer cell, rather than nonspecifically inhibiting and killing all
      rapidly dividing cells, has also been shown to have a potential role in the
      treatment of PH. This drug has been shown to reduce both pulmonary arterial
      smooth muscle cell hypertrophy and hyperplasia in a variety of disease processes.
      We summarize here recent topics regarding PH and advances in treatments for PH,
      particularly pulmonary arterial hypertension, including lung transplantation.

PMID- 21850578
TI  - Molecular oncology of lung cancer.
AB  - Progress in genetic engineering has made it possible to elucidate the molecular
      biological abnormalities in lung cancer. Mutations in KRAS and P53 genes, loss of
      specific alleles, and DNA methylation of the tumor suppressor genes were the
      major abnormalities investigated between 1980 and the 2000s. In 2004, mutations
      in the epidermal growth factor receptor (EGFR) gene that cause oncogene addiction
      were discovered in non-small-cell lung cancers (NSCLCs), especially in
      adenocarcinomas. Because they are strongly associated with sensitivity to EGFR
      tyrosine kinase inhibitors (EGFR-TKIs), a great deal of knowledge has been
      acquired in regard to both EGFR and other genes in the EGFR family and their
      downstream genes. Moreover, in 2007 the existence of the echinoderm microtubule
      associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was
      discovered in NSCLC; and the same as EGFR-TKIs, ALK inhibitors are being found to
      be highly effective in lung cancers that have this translocation. These
      discoveries graphically illustrate that molecular biological findings are
      directly linked to the development of clinical oncology and to improving the
      survival rates of lung cancer patients. Here, we review the remarkable progress
      in molecular biological knowledge acquired thus far in regard to lung cancer,
      especially NSCLC, and the future possibilities.

PMID- 21850580
TI  - High-velocity penetrating thoracic trauma with suspected cardiac involvement in a
      combat support hospital.
AB  - PURPOSE: The most common cardiac injuries in the United States are blunt trauma
      from motor vehicle accidents or low-velocity trauma from stabbings. During
      military conflict, high-velocity injuries, including gunshot wounds (GSW) and
      fragment injury from improvised explosive devices (IED), are relatively more
      common. METHODS: This is a retrospective review of cases with high-velocity
      penetrating injury and suspected myocardial involvement during a 6-month period
      in Baghdad, Iraq, at a United States Army hospital during Operation Iraqi
      Freedom. RESULTS: Eleven cases survived to admission (GSW in 5, IED in 6). The
      mean age of the all-male cohort was 27 years (range, 3-54 years). Eight of the 11
      patients (73%) were victims of polytrauma. The entrance involved the right
      ventricle (n = 3), right atrium (n = 2), left ventricle (n = 1), or mediastinum
      and pericardial reflections (n = 5). Echocardiography was performed in all 11
      patients. In 7 patients, no foreign body was identifiable, and in 2 patients the
      foreign body was identified within the pericardial fat pad. Three patients were
      identified as having a suspected ventricular septal defect, ranging in size from
      2 to 8 mm. The most common electrocardiographic abnormality was atrioventricular
      block and right bundle branch block. In 4 patients, the management of the chest
      injury was nonsurgical, and in 1 patient the treatment was a chest tube only.
      Four of the patients underwent median sternotomy, 1 underwent emergent lateral
      thoracotomy, and 1 underwent an infradiaphragmatic approach. CONCLUSION: This
      case series is too small to draw definitive conclusions; however, a
      multidisciplinary approach to high-velocity injuries with potential for cardiac
      involvement augments preoperative assessment for myocardial injury and may allow
      selective nonoperative management.

PMID- 21850582
TI  - Traumatic rupture of the false lumen in a patient with preexisting chronic
      dissection of the descending thoracic aorta.
AB  - A 63-year-old man was transported to the emergency medical center due to blunt
      chest trauma combined with a fractured left leg caused by a motorcycle accident.
      He complained of severe dyspnea. Contrast-enhanced computed tomography revealed
      chronic aortic dissection DeBakey III, mediastinal hematoma of high density just
      above the diaphragm around the aorta, and an intimal flap-like shadow in the
      false lumen. Traumatic aortic rupture (TAR) with chronic aortic dissection was
      suspected. Aortography showed no clear sign of leakage, but a double-contour
      density was found in the outer wall of the false lumen of the descending aorta
      just above the diaphragm. He was therefore diagnosed with TAR and underwent an
      emergency operation. At the operation, rupture in the outer wall of the
      preexisting false lumen was found and was directly sutured. Acute renal failure
      developed immediately after surgery, which improved after several hemodialyses.
      We consider our case rare because no report has been so far made on TAR with
      chronic dissection.

PMID- 21850581
TI  - Treatment of prosthetic valve endocarditis complicated by destruction of the
      aortic annulus.
AB  - PURPOSE: It has been reported that surgical treatment for prosthetic valve
      endocarditis complicated by destruction of the aortic annulus is associated with
      high mortality and morbidity. The aim of this study was to evaluate the efficacy
      of our surgical strategy for this situation. METHODS: Between October 2003 and
      April 2009, eight patients (mean age 68.6 years) with prosthetic valve
      endocarditis complicated by destruction of the aortic annulus were surgically
      treated at our hospital. We use a relatively simple procedure consisting of a
      patch plasty of the abscess cavity in addition to complete removal of the
      infected tissue of the abscess cavity followed by standard aortic valve
      replacement. All patients had active endocarditis and were in New York Heart
      Association functional class III or IV. Preoperative echocardiography revealed
      that four patients had moderate or severe aortic regurgitation, and two had
      mitral valve endocarditis as well. RESULTS: There were no operative deaths (<=30
      days). Cardiac complications included paroxysmal atrial fibrillation in three
      patients and transient atrioventricular block in one. One patient died of
      multiple organ failure 66 days after the surgery. The overall in-hospital
      mortality was 12.5%. Patients were followed-up for 6-49 months (mean 31 months).
      There was no recurrent prosthetic valve endocarditis. One patient required
      reoperation (mitral annuloplasty and redo aortic valve replacement). There were
      two late deaths: lung cancer in one and multiple organ failure related to
      pneumonia after the aforementioned redo operation in the other. CONCLUSION: Our
      simple procedure for complicated prosthetic valve endocarditis yielded excellent
      early and midterm outcomes.

PMID- 21850583
TI  - A case of pulmonary infective endarteritis associated with patent ductus
      arteriosus: surgical closure under circulatory arrest.
AB  - A 35-year-old man was admitted to the hospital with prolonged high-grade fever.
      Chest computed tomography revealed multiple pulmonary infiltrations in both
      lungs, suggesting septic emboli. Echocardiography revealed patent ductus
      arteriosus and mobile large vegetations in the pulmonary artery. Because of
      uncontrollable infection and the imminent possibility of massive pulmonary
      embolism, he underwent transpulmonary surgical closure of the ductus and
      resection of the vegetations under hypothermic circulatory arrest using
      cardiopulmonary bypass. We report a rare case of open heart surgery in a patient
      with pulmonary infective endarteritis associated with patent ductus arteriosus.

PMID- 21850584
TI  - Acute aortic dissection at 33 weeks of gestation with fetal distress syndrome.
AB  - The present report describes a female patient, 33 weeks pregnant, who
      demonstrated complicated abnormal placenta formation and fetal distress, and who
      presented with an acute type A aortic dissection. The patient underwent an
      immediate cesarean section and hysterectomy followed by a successful emergency
      surgical aortic repair, thereby obtaining a favorable outcome for both mother and
      baby.

PMID- 21850585
TI  - Patch annulo-aortoplasty in an adult patient with congenital supravalvular aortic
      stenosis and a small aortic annulus.
AB  - A 39-year-old woman with familial homozygous hypercholesterolemia had
      supravalvular and valvular aortic stenosis. Modified Nick's procedure and aortic
      valve replacement was performed to relieve both the supravalvular and annular
      stenoses. At surgery, the ascending aorta was found to be narrowing at the level
      of the sinotubular junction, which was compatible with congenital supravalvular
      aortic stenosis. Histological examination of the aortic cusps showed sclerotic
      change due to hypercholesterolemia. These findings indicated that familial
      homozygous hypercholesterolemia caused valvular aortic stenosis and exacerbated
      congenital supravalvular aortic stenosis.

PMID- 21850586
TI  - Castleman's disease of the pleura.
AB  - Castleman's disease is a rare benign disease of the lymph nodes. Its origin from
      the pleura is rare. Surgical excision, when feasible, appears to provide good
      results. We encountered a patient who had the disease arising from the parietal
      pleura. We present the clinical scenario, investigations, and our management of
      the patient.

PMID- 21850587
TI  - Lymphatic and venous malformation or "lymphangiohemangioma" of the anterior
      mediastinum: case report and literature review.
AB  - Lymphatic and venous malformations (LVM) are tumor-like lesions combining
      dysplastic lymphatic and venous vessel structures. They are rarely found in the
      mediastinum. We present a case of mediastinal LVM, with review of the literature.
      An asymptomatic 60-yearold man presented for evaluation of an anterior
      mediastinal mass. On chest computed tomography (CT), the mass demonstrated
      contrast enhancement and its 7-mm vein draining directly into the left
      brachiocephalic vein. The tumor was resected completely using video-assisted
      thoracoscopic surgery. The surgical specimen revealed combined features of venous
      and lymphatic dysplasia, and was diagnosed it as LVM, so-called mediastinal
      lymphangiohemangioma. Management plans based on precise imaging studies using
      magnetic resonance imaging and multi-detector-row CT phlebography could be
      helpful in guiding both preoperative diagnosis and subsequent treatment decisions
      for mediastinal LVM.

PMID- 21850588
TI  - Disseminated calcifying tumor of the pleura: review of the literature and a case
      report with immunohistochemical study of its histogenesis.
AB  - Calcifying tumor of the pleura is a rare benign tumor, similar to the calcifying
      fibrous pseudotumor originally described in the subcutaneous and deep soft
      tissues of the extremities, trunk, and neck. Calcifying tumors of the pleura have
      also been reported infrequently as disseminated lesions. Here we report a case of
      disseminated calcifying tumor of the pleura, with some new findings obtained in
      this study, and review the literature of disseminated calcifying tumor of the
      pleura.

PMID- 21850589
TI  - Invasive thymoma with osseous metaplasia and cystic change in a case of
      myasthenia gravis: a rare presentation.
AB  - A 35-year-old woman, a known case of myasthenia gravis, was found to have an
      anterior mediastinal mass, which was surgically removed. The preoperative
      clinical and radiologic diagnosis was that of a thymoma, but foci of
      calcification and prominent cystic change suggested the remote possibility of a
      teratoma. Histopathologically, it was confirmed to be a type B3 invasive thymoma
      with intratumoral ossification. Up to the present, three cases of thymoma with
      osseous metaplasia, including only one with myasthenia gravis, have been reported
      in the English literature. The present case report highlights the rare occurrence
      of osseous metaplasia in thymomas and the diagnostic challenge that it can pose,
      especially if it is associated with cystic degeneration.

PMID- 21850590
TI  - Complete sternal cleft in an adult: case report.
AB  - A cleft of the sternum is a rare congenital anomaly. We report a rare case of
      complete sternal cleft in a 25-year-old woman. After surgical correction of the
      pectus excavatum, complete closure by direct approximation of the freshened
      sternal remnants to the midline, without interposition of tissue graft or inert
      prosthesis, was achieved in our patient. The functional and cosmetic result was
      excellent after complete healing.

PMID- 21850591
TI  - Comprehensive preassessment form for adult cardiac surgery.
AB  - Comprehensive evaluation of our patients before putting them under "the knife"
      can never be overemphasized. It is our duty to care for the patients. Detailed
      history-taking, clinical examination, and investigations are mandatory prior to
      surgery. For many years, we have striven to make our method thorough and safe for
      all patients. We propose here a simple, comprehensive preassessment form that is
      easily applicable in any unit.

PMID- 21850593
TI  - CsICE1 and CsCBF1: two transcription factors involved in cold responses in
      Camellia sinensis.
AB  - C-repeat/dehydration-responsive element binding factors (CBFs) can induce the
      expression of a suite of cold-responsive genes to increase plant cold tolerance,
      and inducer of CBF expression 1 (ICE1) is a major activator for CBF. In the
      present study, we isolated the full-length cDNAs of ICE1 and CBF from Camellia
      sinensis, designated as CsICE1 and CsCBF1, respectively. The deduced protein
      CsICE1 contains a highly conserved basic helix-loop-helix (bHLH) domain and C
      terminal region of ICE1-like proteins. CsCBF1 contains all conserved domains of
      CBFs in other plant species and can specifically bind to the C-repeat/dehydration
      responsive element (CRT/DRE) as confirmed by electrophoretic mobility shift
      assay. The transcription of CsICE1 had no apparent alteration after chilling
      treatment (4 degrees C). CsCBF1 expression was not detected in normal temperature
      (20 degrees C) but was induced immediately and significantly by low temperature
      (4 degrees C). Our results suggest that ICE1-CBF cold-response pathway is
      conserved in tea plants. CsICE1 and CsCBF1, two components of this pathway, play
      roles in cold responses in tea plants.

PMID- 21850594
TI  - C-value reassessment of plant standards: an image cytometry approach.
AB  - Image cytometry (ICM) has been used to measure DNA 2C-values by evaluating the
      optical density of Feulgen-stained nuclei. This optical measurement is carried
      out using three basic tools: microscopy, digital video camera, and image analysis
      software. Because ICM has been applied to plants, some authors have remarked that
      studies should be performed before this technique can be accepted as an accurate
      method for determination of plant genome size. Based on this, the 2C-value of
      eight plants, which are widely used as standards in DNA quantifications, was
      reassessed in a cascade-like manner, from A. thaliana through R. sativus, S.
      lycopersicum, Glycine max, Z. mays, P. sativum, V. faba, to A. cepa. The mean 2C
      values of all plants were statistically compared to the values reported by other
      authors using flow cytometry and/or ICM. These analyses demonstrated that ICM is
      an accurate and reliable method for 2C-value measurement, representing an
      attractive alternative to flow cytometry. Statistical comparison of the results
      also indicated Glycine max 'Polanka' as the most adequate primary standard.
      However, distinct authors have been advised that 2C DNA content of the reference
      standard should be close to that of the sample. As three further approaches also
      revisited the 2C-value of these eight plants, we have thus proposed a mean 2C
      value for each eight species.

PMID- 21850595
TI  - Transgenic rice plants harboring the grain hardness-locus region of Aegilops
      tauschii.
AB  - Grain hardness of wheat is determined by the hardness (Ha)-locus region, which
      contains three friabilin-related genes: puroindoline-a (Pina), puroindoline-b
      (Pinb) and GSP-1. In our previous study, we produced the transgenic rice plants
      harboring the large genomic fragment of the Ha-locus region of Aegilops tauschii
      containing Pina and GSP-1 genes by Agrobacterium-mediated transformation. To
      examine the effects of the transgenes in the rice endosperms, we firstly
      confirmed the homozygosity of the T-DNAs in four independent T2 lines by using
      fluorescence in situ hybridization (FISH) and DNA gel blot analyses. The
      transgenes, Pina and GSP-1, were stably expressed in endosperms of the T3 and T4
      seeds at RNA and protein levels, indicating that the promoters and other
      regulatory elements on the wheat Ha-locus region function in rice, and that
      multigene transformation using a large genomic fragment is a useful strategy. The
      functional contribution of the transgene-derived friabilins to the rice endosperm
      structure was considered as an increase of spaces between compound starch
      granules, resulting in a high proportion of white turbidity seeds.

PMID- 21850596
TI  - Expression of KxhKN4 and KxhKN5 genes in Kalanchoe blossfeldiana 'Molly' results
      in novel compact plant phenotypes: towards a cisgenesis alternative to growth
      retardants.
AB  - Many potted plants like Kalanchoe have an elongated natural growth habit, which
      has to be controlled through the application of growth regulators. These
      chemicals will be banned in the near future in all the EU countries. Besides
      their structural functions, the importance of homeotic genes to modify plant
      architecture appears evident. In this work, the full length cDNA of five KNOX
      (KN) genes were sequenced from K. x houghtonii, a viviparous hybrid. Two
      constructs with the coding sequence of the class I and class II homeobox KN
      genes, KxhKN5 and KxhKN4, respectively, were overexpressed in the commercially
      important ornamental Kalanchoe blossfeldiana 'Molly'. Furthermore, a post
      transcriptional gene silencing construct was made with a partial sequence of
      KxhKN5 and also transformed into 'Molly'. Several transgenic plants exhibited
      compact phenotypes and some lines had a relative higher number of inflorescences.
      A positive correlation between gene expression levels and the degree of
      compactness was found. However, a correlation between the induced phenotypes and
      the number of inserted copies of the transgene were not observed, although line
      '70-10' with a high copy number also had the highest expression level. Moreover,
      overexpression of KxhKN4 resulted in plants with dark green leaves due to an
      elevated content of chlorophyll, a highly desired property in the ornamental
      plant industry. These transgenic plants show that a cisgenesis approach towards
      production of compact plants with improved quality as an alternative to chemical
      growth retardants may be feasible.

PMID- 21850597
TI  - Population genetic analyses of the AmpFlSTR(r) NGMTM in Brazil.
AB  - Population data of 15 short tandem repeat loci of the AmpFlSTR(r) next generation
      multiplex (NGM)TM were obtained from a sample of 835 individuals. The loci are
      the ten short tandem repeats (STRs) in the SGM Plus(r) Kit plus the EDNAP- and
      ENSFI-recommended STRs D10S1248, D22S1045, D2S441, D1S1656, and D12S391. Allele
      frequency and other forensically relevant statistics data were generated for the
      NGM loci into five current country macroregions of Brazil (North, Northeast,
      Central West, Southeast, and South). All the analyzed loci meet Hardy-Weinberg
      equilibrium expectations and no linkage disequilibrium in all pairs of loci. The
      observed and expected heterozygosity, power of discrimination, polymorphic
      information content, and the other population-genetic indices were calculated.
      The overall power of discrimination was greater than 0.99999999999999999996 and
      the combined power of exclusion was greater than 0.9999998 in all Brazilian
      populations. Comparative analysis between populations from different Brazilian
      macroregions as well as between Brazil and Caucasian, African Americans, and
      Hispanic US populations are presented.

PMID- 21850598
TI  - Ten years after arterial bypass surgery for claudication: venous bypass is the
      primary procedure for TASC C and D lesions.
AB  - BACKGROUND: The appropriate role for surgery and endovascular therapy for severe
      intermittent claudication (IC) remains controversial. We present our results
      after infrainguinal autogenous bypass for severe IC more than 10 years ago giving
      a reasoned argument to perform vein bypass as the primary procedure for severe
      IC. METHODS: Our prospectively designed database includes more than 1,000
      infrainguinal bypasses following an all-autogenous policy. For this review only
      patients operated on for severe IC at least 10 years ago were included. The
      primary end points were survival and primary and assisted-primary patency rates.
      RESULTS: From October 1988 until December 2000, 124 bypasses for IC were
      performed. Ninety-five patients were male and the mean age was 64.5 +/- 10.8
      years. Survival after 10 years was 50.3% according to life table analysis. Forty
      bypasses were to the supragenicular artery, 62 to the infragenicular popliteal
      artery, and 22 to the tibial artery. Thirty-day mortality was 0.8% (1 patient).
      The primary patency rate after 10 years was 63.5% and the assisted-primary
      patency rate 87.3%. CONCLUSION: Infrainguinal venous bypass for severe IC has
      excellent long-term results. Our results are strong arguments against the liberal
      use of stenting long lesions of the femoropopliteal artery. Venous bypass remains
      the primary procedure for TASC C and D lesions in claudicants.

PMID- 21850599
TI  - Long-term outcomes of extended proximal gastrectomy for oesophagogastric
      junctional tumours.
AB  - BACKGROUND: There is no consensus on the optimum approach for resection of
      oesophagogastric junctional (OGJ) tumours. We prospectively evaluated the
      efficacy of transabdominal radical extended proximal gastrectomy with
      oesophagogastric anastomosis (EPGOG) for selected tumours of the OGJ. METHODS:
      Between 1998 and 2007, 66 selected consecutive patients with tumours of the OGJ
      underwent successful EPGOG. Selection was limited to tumours where the maximal
      proximal extent was 36 cm ab oral. Pre-, peri-, and postoperative outcomes
      together with long-term survival data for these patients were prospectively
      collected. RESULTS: Median theatre time was 242 min (range = 120-480), with a
      median blood loss of 300 ml (range = 50-1720). Eighty-nine percent of patients
      were extubated in theatre; major complications occurred in 9 (14%) patients, with
      an overall in-hospital mortality rate of 8%. Thirty-five (53%) patients had nodal
      disease and the median lymph node yield was 13 (range = 4-36), with an R0
      resection rate of 80%. In terms of long-term outcomes, the 2- and 5-year
      actuarial survival rates were 54 +/- 6% and 41 +/- 6%. CONCLUSION: Extended
      radical proximal gastrectomy with oesophagogastric anastomosis for selected
      junctional tumours is a feasible technique which does not compromise oncological
      principles as evidenced by an excellent long-term survival rate.

PMID- 21850600
TI  - Fine-tuning the truth.

PMID- 21850601
TI  - Tertiary survey performance in a regional trauma hospital without a dedicated
      trauma service.
AB  - BACKGROUND: Initial management of trauma patients is focused on identifying life-
      and limb-threatening injuries and may lead to missed injuries. A tertiary survey
      can minimise the number and effect of missed injuries and involves a physical re
      examination and review of all investigations within 24 h of admission. There is
      little information on current practice of tertiary survey performance in
      hospitals without a dedicated trauma service. We aimed to determine the rate of
      tertiary survey performance and the detail of documentation as well as the
      baseline rate of missed injuries. METHODS: We performed a retrospective,
      descriptive study of all multitrauma patients who presented to an Australian
      level II regional trauma centre without a dedicated trauma service between May
      2008 and February 2009. A medical records review was conducted to determine
      tertiary survey performance and missed injury rate. RESULTS: Of 252 included
      trauma patients, 20% (n = 51) had a tertiary survey performed. A total of nine
      missed injuries were detected in eight patients (3.2%). Of the multiple
      components of the tertiary survey, most were poorly documented. Documentation was
      more comprehensive in the subgroup of patients who did have a formal tertiary
      survey. CONCLUSIONS: Tertiary survey performance was poor, as indicated by low
      documentation rates. The baseline missed injury rate was comparable to previous
      that of retrospective studies, although in this study an underestimation of true
      missed injury rates is likely. Implementing a formal, institutional tertiary
      survey may lead to improved tertiary survey performance and documentation and
      therefore improved trauma care in hospitals without a dedicated trauma service.

PMID- 21850602
TI  - Unplanned reoperation and reintervention after pancreatic resections: an analysis
      of risk factors.
AB  - BACKGROUND: The purpose of the study was to determine the incidence of any
      unplanned reoperation or reintervention procedure after pancreatic resection and
      to identify the underlying risk factors. METHODS: A total of 189 consecutive
      pancreatic resections performed from 2001-2008 were searched for any unplanned
      reoperation, percutaneous drainage, or angiographic reintervention. A
      retrospective analysis of a prospectively maintained database, including patient
      characteristics, comorbidities, details of surgery, specific complications,
      incidence of reoperation/reintervention, and mortality was performed. RESULTS:
      Overall rates of reoperation, reintervention, and mortality were 6.3% (12/189),
      7.9% (15/189), and 1.6% (3/189), respectively. Four patients underwent
      reintervention and reoperation, so the combined reoperation/reintervention rate
      was 12.2% (23/189). Reoperation (P < 0.001) and reintervention (P = 0.002)
      correlated with mortality. Hemorrhage (relative risk [RR], 58; P = 0.0017) and
      the combination of hemorrhage and pancreatic fistula (RR, 117; P < 0.0001) were
      identified as risk factors for unplanned reoperation, hemorrhage (RR, 82; P =
      0.005), pancreatic fistula (RR, 42; P < 0.001), and the combination of both
      complications (RR, 246; P < 0.001) for reoperation and/or reintervention. Other
      patient- or procedure-related factors did not influence the reoperation and/or
      reintervention rates significantly. CONCLUSIONS: Pancreatic fistula and
      hemorrhage are the predominant factors that afford unplanned
      reoperation/reintervention. Although reporting the incidence of unplanned
      reoperation will include the most severe postoperative complications, a
      considerable number of reinterventions are missed. Therefore, in outcome analyses
      of pancreatic surgery, not only reoperations but also any interventional
      therapies should be included.

PMID- 21850603
TI  - Delayed primary closure of the septic open abdomen with a dynamic closure system.
AB  - BACKGROUND: The major challenge in the management of patients with an infected
      open abdomen (OA) is to control septic peritonitis and intra-abdominal fluid
      secretion, and to facilitate repeated abdominal exploration, while preserving the
      fascia for delayed primary closure. We here present a novel method for closure of
      the infected OA, based on continuous dynamic tension, in order to achieve re
      approximation of the fascial edges of the abdominal wall. METHODS: Eighteen cases
      with severe peritonitis of various origin (e.g., gastrointestinal perforations,
      anastomotic leakage) were primarily stabilized by laparostomy, sealed with either
      the vacuum-assisted closure abdominal dressing or the Bogota bag. After
      hemodynamic stabilization and control of the sepsis, the Abdominal Re
      approximation Anchor System (ABRA; Canica Design, Almonte, Ontario, Canada) was
      applied. This system approximates the wound margins through dynamic traction
      exerted by transfascial elastomers. Before ABRA application, 5/18 patients had a
      grade 2B, 2/18 a grade 3, and 11/18 a grade or 4 status according to the open
      abdomen classification of Bjorck. RESULTS: In this severely ill population the
      mean time before ABRA system application was 12 days (range: 2-39 days). Two of
      18 patients died of non-ABRA-related causes within three weeks. In 14 of the
      remaining 16 patients (88%) primary abdominal closure of the midline was
      accomplished in 15 days (range: 7-30 days). The other two patients needed a
      component separation technique according to Ramirez to reach closure. However,
      secondary wound dehiscence occurred in both these patients. Two thirds of
      patients (12/18) developed pressure sores to the skin and/or dermis, but all
      healed without further complications. During outpatient clinic follow-up, 4/14
      successfully closed patients still developed a midline hernia. CONCLUSIONS:
      Delayed primary closure of OA in septic patients could be achieved in 88% with
      this new approximation system. However, the risk of hernia development remained.
      We consider this system a useful tool in the treatment of septic patients with an
      open abdomen.

PMID- 21850604
TI  - Pancreatic cancer, healthcare cost, and loss of productivity: a register-based
      approach.
AB  - BACKGROUND: Despite the fact that pancreatic cancer is the fourth leading cause
      of cancer-related death, there is little empirical evidence on its direct
      healthcare costs and, especially, its indirect costs due to loss of production.
      METHODS: The present study is a retrospective analysis of all patients with
      pancreatic cancer (excluding endocrine cancer) in the primary catchment area of
      Lund University Hospital, Sweden, during the period 2005-2007. Detailed
      information on all diagnostic and therapeutic investigations, interventions, and
      postoperative course and long-term follow-up was collected, as well as
      absenteeism from work due to the health problem, from which direct costs were
      calculated. The indirect costs for loss of production due to sickness and
      premature death were calculated by the human capital method. A total of 83
      patients were included, for an incidence rate of 9.9 patients/100,000
      inhabitants. RESULTS: Direct treatment cost per pancreatic-cancer patient was
      estimated at EUR 16,066 for each patient's remaining lifetime. Hospitalization
      accounted for the major expenditure-60% of the lifetime treatment cost. Patients
      with resectable tumor had a mean cost of EUR 19,809; locally advanced disease,
      EUR 14,899; and metastatic disease, <euro>16,179. Younger patients and men had a
      higher than average lifetime treatment cost. The loss of productivity was
      estimated at EUR 287,420 per patient younger than 65 years of age, of which
      premature mortality accounted for 79%. CONCLUSIONS: Adding the cost of palliative
      care estimated in a previous Swedish study, health-care costs and productivity
      losses for pancreatic cancer would add up to a substantial economic burden for
      Sweden at large in 2009 (population 9.1 million), between EUR 86 million and EUR
      93 million.

PMID- 21850605
TI  - Accuracy of macroscopic intraoperative diagnosis of serosal invasion and risk of
      over- and underestimation in gastric carcinoma.
AB  - BACKGROUND: Accurate intraoperative diagnosis of serosal invasion is a
      prerequisite for proper application of invasive procedures, such as
      intraperitoneal chemohyperthermia, for serosa positive gastric carcinomas.
      METHODS: We reviewed the prospectively constructed data of 1,265 gastric cancer
      patients who underwent surgery between 2007 and 2009. Accuracies of macroscopic
      diagnoses of serosal invasion were determined by comparing with pathological
      findings. The risk factors of over- and underestimation of serosal invasion were
      analyzed in the univariate and multivariate model. RESULTS: The accuracy of
      macroscopic intraoperative diagnosis of serosal invasion was 88%. Serosal
      invasion was underestimated in 34 of 187 serosa positive patients and
      overestimated in 117 of 1,078 serosa negative patients; a sensitivity and
      specificity of 82 and 89%, respectively. When pT1 tumors were excluded, the
      accuracy, sensitivity, and specificity of macroscopic diagnosis of serosal
      invasion were 71.5, 81.8, and 65.3%, respectively. Univariate and multivariate
      analysis revealed that a tumor size of >4 cm and preoperative CT finding of
      serosa positive were independent risk factors for macroscopic overestimation as
      serosal invasion in pT2 gastric cancer. Meanwhile, Borrmann type 1, preoperative
      CT finding of serosa negative, lesser/posterior surface location, and tumor size
      of <4 cm were independent risk factors for underestimation of serosal invasion in
      pT3 gastric carcinoma. CONCLUSIONS: The macroscopic diagnosis of serosal invasion
      is largely consistent with pathological findings. However, great care should be
      taken with regard to the risk of over- and underestimation of serosal invasion
      when making a decision for invasive treatments based on macroscopic findings of
      serosal invasion.

PMID- 21850607
TI  - Ethnic disparities in self-reported oral health status and access to care among
      older adults in NYC.
AB  - There is a growing burden of oral disease among older adults that is most
      significantly borne by minorities, the poor, and immigrants. Yet, national
      attention to oral heath disparities has focused almost exclusively on children,
      resulting in large gaps in our knowledge about the oral health risks of older
      adults and their access to care. The projected growth of the minority and
      immigrant elderly population as a proportion of older adults heightens the
      urgency of exploring and addressing factors associated with oral health-related
      disparities. In 2008, the New York City Health Indicators Project (HIP) conducted
      a survey of a representative sample of 1,870 adults over the age of 60 who
      attended a random selection of 56 senior centers in New York City. The survey
      included questions related to oral health status. This study used the HIP
      database to examine differences in self-reported dental status, dental care
      utilization, and dental insurance, by race/ethnicity, among community-dwelling
      older adults. Non-Hispanic White respondents reported better dental health,
      higher dental care utilization, and higher satisfaction with dental care compared
      to all other racial/ethnic groups. Among minority older adults, Chinese
      immigrants were more likely to report poor dental health, were less likely to
      report dental care utilization and dental insurance, and were less satisfied with
      their dental care compared to all other racial/ethnic groups. Language fluency
      was significantly related to access to dental care among Chinese immigrants.
      Among a diverse community-dwelling population of older adults in New York City,
      we found significant differences by race/ethnicity in factors related to oral
      health. Greater attention is needed in enhancing the cultural competency of
      providers, addressing gaps in oral health literacy, and reducing language
      barriers that impede access to care.

PMID- 21850606
TI  - Does PEG use cause dysphagia in head and neck cancer patients?
AB  - Percutaneous endoscopic gastrostomy (PEG) use is common in patients who undergo
      radiotherapy (RT) for head and neck cancer to maintain weight and nutrition
      during treatment. However, the true effect of PEG use on weight maintenance and
      its potential impact on long-term dysphagia outcomes have not been adequately
      studied. This retrospective study looked at swallowing-related outcomes among
      patients who received prophylactic PEG vs. those who did not, and among patients
      who maintained oral diets vs. partial oral diets vs. those who were nil per os
      (NPO). Outcomes were assessed at the end of RT and at 3, 6, and 12 months post
      RT. A comprehensive review of patients' medical charts for a 6-year period
      yielded 59 subjects with complete data. Results showed no difference in long-term
      percent weight change between the prophylactic PEG patients vs. all others, or
      between patients who, during RT, had oral diets vs. partial oral diets vs. NPO.
      However, those who did not receive prophylactic PEGs and those who maintained an
      oral or a partial oral diet during RT had significantly better diet outcomes at
      all times post RT. Dependence on a PEG may lead to adverse swallowing ability in
      post-irradiated head and neck cancer patients possibly due to decreased use of
      the swallowing musculature.

PMID- 21850608
TI  - [LASIK - a new treatment or the standard].
AB  - Classification of LASIK in refractive surgery and treatment by health insurance,
      and education by the physician. Results in clinical studies and case law in
      Germany 2010.

PMID- 21850609
TI  - The first bis-retrochalcone from Fissistigma latifolium.
AB  - Two novel chalconoids, [3-3'']bi-2-hydroxy-4,5,6-trimethoxydihydrochalcone (1)
      and 4,6-dimethoxy-2,5-quinodihydrochalcone (2), and twelve known compounds were
      isolated from the methanolic extract of Fissistigma latifolium (Dun.) Merr. The
      structures of all compounds were determined by spectroscopic methods. Of these,
      compounds 1, 2, and 2-hydroxy-4,5,6-trimethoxydihydrochalcone (10) belong to an
      uncommon group of chalconoids, the retrochalcones. Compound 1 is the first bis
      retrochalcone to be reported, and compound 2 is a quinoretrochalcone.
      Furthermore, 2 showed activity against the MDA-MB-231 human breast cancer cell
      line with an IC (50) value of 7.1 uM.

PMID- 21850610
TI  - [Is high resolution ultrasound of the median nerve helpful before reintervention
      after failed carpal tunnel surgery?].
AB  - A common reason for persisting or new complaints after carpal tunnel surgery is
      an incomplete release of the retinaculum flexorum. Traction neuropathy, a real
      recurrent carpal tunnel syndrome and iatrogenic nerve lesions occur less
      frequently. In the case of an incomplete release of the flexor retinaculum the
      clinical symptoms in most of the patients can be resolved with revision surgery.
      Electrodiagnostic testing can only support the indication for a reoperation if a
      preoperative examination exists but is not able to demonstrate the exact cause of
      a failed carpal tunnel surgery. The 4 cases presented here show that high
      resolution ultrasound provides valuable information in addition to
      electrodiagnostic testing before a reintervention.

PMID- 21850611
TI  - [Pyogenic granuloma of the thumb following the bite of a sheep].
AB  - In the case of a patient with a large pyogenic granuloma of the thumb about three
      months after the bite of a sheep, we covered the defect after resection with a
      split thickness skin graft. Although at first amputation was discussed, after a
      few months a very good functional and aesthetic result was achieved.

PMID- 21850612
TI  - [Intraneural lipoma of the median nerve].

PMID- 21850613
TI  - [T-cartilage tympanoplasty for an open oval window].
AB  - A T shaped cartilage, placed into the open oval window, functions as a stapes.
      The transvers part of the T prevents a too deep insertion into the vestibule. If
      necessary small stripes of connective tissue seal the vestibule.

PMID- 21850614
TI  - [Results of transoral laser resection in T1-2 oropharyngeal, hypopharyngeal and
      laryngeal carcinomas].
AB  - BACKGROUND: Transoral laser microsurgery (TLM) has led to an expansion of the
      therapeutic modalities for malignomas of head and neck. This study aims to assess
      the oncologic results and functional outcomes of TLM in early carcinomas.
      PATIENTS AND METHODS: This is a retrospective study of 947 cases with T1-2
      carcinomas primarily managed with laser surgery between 1979 and 2007. All cases
      were assessed for survival, with respect to location, T and N classification and
      status of surgical margins. Cases were additionally evaluated for incidence of
      major complications and retention of laryngeal and pharyngeal function. RESULTS:
      Disease specific survival was 78.6% for oropharyngeal, 68.9% for hypopharyngeal,
      82.3% for supraglottic und 95.2% for glottis carcinomas. Survival estimates were
      found to be significantly better for cases without cervical metastasis and with
      negative surgical margins. A low rate of major complications (4.7%) were noted.
      1% of the patients had a permanent dysfunction of swallowing and 1.1 % needed a
      permanent tracheostomy. CONCLUSION: Laser surgery appears to be a very effective
      management modality for small carcinomas of the head and neck as long as clear
      surgical margins can be achieved. This technique offers acceptable oncologic
      results with a low incidence of complications and satisfactory retention of
      function.

PMID- 21850615
TI  - Radial vs femoral approach with StarClose clip placement for primary percutaneous
      coronary intervention in patients with ST-elevation myocardial infarction.
      RADIAMI II: a prospective, randomised, single centre trial.
AB  - BACKGROUND: Compared to the transfemoral approach (TFA), the transradial approach
      (TRA) for primary percutaneous coronary intervention (PCI) is associated with
      less risk of access site complications, greater patient comfort and faster
      mobilisation. Using vascular closure devices during TFA can offer similar
      advantages. AIM: To compare the results of TRA and TFA using a StarClose device
      for primary PCI in patients with ST-elevation myocardial infarction (STEMI).
      METHODS: Patients were randomised to PCI using TRA (n = 49) or PCI using TFA and
      StarClose (n = 59). RESULTS: Door-to-balloon inflation time was 67.4 +/- 17.1 vs
      57.5 +/- 17.5 min (p = 0.009) in the TRA and TFA groups respectively. Procedural
      success rate was 100% and 98.3%, respectively (NS). There were no significant
      differences in the incidence of major adverse cardiac events (MACE) or bleeding
      complications between the groups: 2.1% and 8.2% in the TRA group vs 1.7% and
      10.2% in the TFA group (NS). Time to resume an upright position and time to full
      mobility was comparable in both groups. CONCLUSIONS: The TRA for PCI in patients
      with STEMI is related to a significantly longer door to balloon time compared to
      the TFA. This had no influence on the incidence of MACE. The duration and
      efficacy of PCI were comparable in both groups. Using StarClose after PCI
      performed via the TFA resulted in an incidence of access site and bleeding
      complications comparable to that found when using TRA.

PMID- 21850616
TI  - [Femoral access or radial--time to change habits].

PMID- 21850617
TI  - The effects of acute hyperglycaemia on the in-hospital and long-term prognosis in
      patients with an acute coronary syndrome--a pilot study.
AB  - BACKGROUND: Acute hyperglycaemia is an adverse prognostic factor in patients with
      acute coronary syndrome (ACS). It is unclear whether these negative effects apply
      equally to patients with diabetes mellitus (DM) and non-DM patients. AIM: To
      evaluate the short-term (in-hospital) and long-term (four-year) prognostic value
      of acute hyperglycaemia in ACS patients with or without DM. METHODS: The study
      involved 116 ACS patients admitted between 2004 and 2006 to our department, who
      were selected for invasive treatment and who had both admission and first fasting
      glucose levels measured. Patients were classified as DM (n = 23), on the basis of
      a known history of diabetes or newly detected diabetes, or non-DM (n = 93). Acute
      hyperglycaemia was defined as an admission glycaemia >= 10.0 mmol/L (180 mg/dL)
      for non-DM patients, or >= 7.8 mmol/L (140 mg/dL) for DM patients, or a first
      fasting glucose level >= 5.6 mmol/L (100 mg/dL) for both DM and non-DM patients.
      The primary end-point was defined as mortality during follow-up. The secondary
      end-points were death, cardiac arrest or repeated ACS occurrence, stroke or
      transient ischaemic attack, and the need for repeat percutaneous coronary
      intervention (PCI) or coronary artery bypass grafting (CABG) procedure during the
      in-hospital and four-year post-hospital periods. During follow-up, patients were
      assessed for a composite end-point defined as all-cause death, repeated ACS
      occurrence, repeat PCI or CABG procedure, and stroke. RESULTS: Acute
      hyperglycaemia was present in 28 non-DM and 14 DM patients. The mean follow-up
      time was 4 +/- 0.6 years. For DM patients, there was no significant difference in
      four-year mortality between hyperglycaemic and normoglycaemic patients (14.3% vs
      11.1%, respectively; NS). The occurrence of secondary end-points and composite
      end-point frequency was also similar for these subgroups, both for in-hospital
      and four-year observations. For non-DM patients, the four-year mortality was
      similar for hyperglycaemic and normoglycaemic subjects (17.9% vs 10.8%,
      respectively; NS), whereas cardiac arrest during the in-hospital period was more
      common for hyperglycaemic than normoglycaemic patients (3.6% vs 0.0%,
      respectively; n = 1 vs 0; p = 0.01). The composite end-point for the in-hospital
      period was reached by 17.6% of hyperglycaemic and 13.8% of normoglycaemic non-DM
      patients (NS). The composite end-point during the four-year observation period
      was more frequently reached in hyperglycaemic than in normoglycaemic non-DM
      patients (78.6% vs 56.9%, respectively; p = 0.04). CONCLUSIONS: Acute
      hyperglycaemia in non-DM patients hospitalised due to ACS was found to be an
      unfavourable long-term (four-year) risk factor, and may also be an unfavourable
      in-hospital risk factor. In contrast, acute hyperglycaemia did not affect
      cardiovascular outcomes in DM patients.

PMID- 21850618
TI  - [Should acute and chronic hyperglycemia be differentiated in patients with acute
      coronary syndromes?].

PMID- 21850619
TI  - Gender-related differences in clinical course, therapeutic approach and prognosis
      in patients with non-ST segment elevation myocardial infarction.
AB  - BACKGROUND: There is accumulated evidence that clinical course and prognosis
      after myocardial infarction (MI) may differ between genders. AIM: To compare
      epidemiology, the clinical course, therapeutic approach and prognosis in men and
      women with non-ST segment elevation MI (NSTEMI). METHODS: We analysed a total of
      1219 consecutive patients with NSTEMI (43% women) treated between June 01, 2005
      and May 31, 2006 in a hospital covering in a district with 1,300,000 inhabitants.
      The data were obtained from the Polish Registry of Acute Coronary Syndromes (PL
      ACS). RESULTS: Women in the study group were on average 6 years older than men
      (72.6 +/- 10.3 vs 66.7 +/- 11.4 years; p < 0.0001). The incidence of arterial
      hypertension (83.4% vs 73.45%; p < 0.0001), diabetes mellitus (30.2% vs 20.1%; p
      < 0.0001) and obesity (17.9% vs 13.1%; p < 0.020) was higher in women, while
      cigarette smoking was more common in men (7.4% vs 32.9%; p < 0.0001). Clinical
      presentation was similar in both genders. Coronary angiography was performed in
      360 patients, more frequently in men (32.8% vs 25.2%; p < 0.05). Less women than
      men underwent percutaneous coronary angioplasty (18.9% vs 12.6%; p < 0.0033). In
      hospital, 30-day and 6-month mortality was similar in both genders (5.3% vs 4.9%;
      6.9% vs 7.3%; and 13.2% vs 13.1%, respectively). In a multivariate analysis,
      female gender did not influence the prognosis. CONCLUSIONS: Although women with
      NSTEMI had worse baseline characteristic and less frequently underwent
      revascularisation, their outcomes were comparable with those in men.

PMID- 21850620
TI  - [Is the female sex a risk factor for acute coronary syndrome?].

PMID- 21850621
TI  - Efficacy of invasive treatment and the occurrence of cardiac rupture in acute ST
      elevation myocardial infarction.
AB  - BACKGROUND: Cardiac rupture is a rare but potentially lethal complication of
      acute myocardial infarction with ST-elevation (STEMI). Primary percutaneous
      coronary intervention (pPCI) is a preferable treatment method of acute STEMI.
      Reperfusion at vascular and myocardial levels may be the key parameters
      determining probability of cardiac rupture. AIM: To analyse the relationship
      between reperfusion parameters and cardiac rupture occurrence in a group of
      patients with STEMI treated with pPCI. METHODS: Twenty three patients with
      cardiac rupture were selected out of 2800 patients with acute STEMI hospitalised
      and treated with pPCI from 2000 to 2007. Free wall or interventricular septum
      rupture was diagnosed on echocardiography or autopsy. The control group consisted
      of 255 patients with STEMI and pPCI treatment, but without cardiac rupture. The
      TIMI flow score was used to assess blood flow in an infarct-related artery (IRA).
      Myocardial perfusion was evaluated with the use of the myocardial blush grade
      (MBG) score. RESULTS: Female gender accounted for 47.8% of patients with cardiac
      rupture. Mean age was 72.9 +/- 4.8 years for women and 64.3 +/- 11.5 years for
      men. In 12 (52%) patients anterior descending artery was the IRA. Before the
      pPCI, the average blood flow in IRA was significantly lower in patients with
      subsequent cardiac rupture (0.41 +/- 0.59) than in the reference group (0.81 +/-
      1.15; p < 0.05), and remained lower after pPCI (1.96 +/- 0.93 in comparison to
      2.93 +/- 0.36; p < 0.05). Adequate blood flow (TIMI 3) was achieved only in 30.4%
      (7) of patients with cardiac rupture and in 95.3% (243) of the control group (p <
      0.05). Myocardial tissue perfusion, assessed by MBG, was also lower (0.76 +/- 1
      vs 1.92 +/- 1.13; p < 0.05). In-hospital mortality in patients with cardiac
      rupture reached 56.5% (13 subjects) compared to 3 (1.2%) patients in the
      reference group (p < 0.05). Multivariable analysis confirmed independent effects
      of lower TIMI and MBG after PCI as well as female gender on the occurrence of
      cardiac rupture. CONCLUSIONS: Poorer blood flow in IRA and worse tissue
      microvascular perfusion after pPCI are important risk factors of cardiac rupture
      occurrence in patients with STEMI.

PMID- 21850622
TI  - [Heart rupture complicating acute myocardial infarction--can it be predicted?].

PMID- 21850623
TI  - Plasma visfatin and tumor necrosis factor-alpha (TNF-alpha) levels in metabolic
      syndrome.
AB  - BACKGROUND: Experimental studies have shown that tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) downregulate visfatin gene expression in
      adipocytes. On the other hand, the induction of cytokine production by visfatin
      in leucocytes and monocytes has also been described. AIM: To assess the possible
      interrelation between plasma concentrations of visfatin and TNF-alpha and TNF
      soluble receptor in obese women fulfilling, or not, the criteria of metabolic
      syndrome (MS). METHODS: Ninety two obese women were included in the study.
      Metabolic syndrome, based on IDF criteria (2005) was diagnosed in 71 subjects
      (mean age 53 +/- 9 years; body mass index 39.1 +/- 5.6 kg/m(2), waist
      circumference 109.6 +/- 11.4 cm). The remaining 21 formed the non-MS subgroup
      (mean age 52 +/- 9 years, body mass index 36.3 +/- 5.2 kg/m(2), waist
      circumference 104.7 +/- 11.0 cm). Fourteen healthy normal weight women served as
      controls. In all subjects, body composition was assessed by the bioimpedance
      method. RESULTS: In the MS subgroup, but not in the non-MS subgroup, visfatin
      levels were significantly higher than in controls. We did not observe any
      significant difference in plasma concentrations of visfatin, TNF-alpha or sTNFRs
      between the MS subgroup and the non-MS subgroup. Only in the MS subgroup and in
      the combined analysis of all study subgroups did plasma visfatin concentrations
      correlate significantly with TNF-alpha levels (R = 0.31, p = 0.01, R = 0.21, p =
      0.03; respectively). Additionally, in the MS subgroup there was a positive
      correlation between visfatin levels and insulin resistance (R = 0.53, p = 0.01).
      CONCLUSIONS: Our findings suggest that visfatin in metabolic syndrome should be
      regarded as a proinflammatory factor indirectly favouring the development of
      insulin resistance.

PMID- 21850624
TI  - [Visfatin--what is currently known about its role in physiology and pathology?].

PMID- 21850625
TI  - Exercise capacity and the quality of life late after surgical correction of
      congenital heart defects.
AB  - BACKGROUND: The long-term impact of surgical correction of congenital heart
      defects (CHD) on exercise capacity and quality of life (QoL) has not been well
      established. AIM: To evaluate exercise capacity, QoL, physical activity and
      depression in young adult patients with a history of congenital heart defect
      surgery (GUCH) for simple left-to-right shunts, and to compare these parameters
      with those obtained in healthy volunteers. METHODS: The study group consisted of
      30 young adults with congenital heart defects (14 males, 16 females), aged 18-36
      (mean 24.6) years who underwent corrective cardiac surgery at least 10 years
      earlier. The control group comprised 30 healthy students (15 males, 15 females),
      aged 21-28 (mean 24.4) years. We performed cardiopulmonary exercise testing on
      bicycle ergometer, QoL and physical activity tests, and depression inventory.
      RESULTS: In young adult GUCH patients the exercise parameters were lower when
      compared to healthy peers. The Stanford questionnaire showed that physical
      activity was diminished as well as QoL in EuroQoL5 test. The Beck inventory
      showed more expressed depression in GUCH group. CONCLUSIONS: The exercise
      capacity, physical activity and QoL of young adults with a history of surgical
      treatment of CHD are worse than observed in healthy peers, and the health status
      does not fulfil the definition of complete recovery.

PMID- 21850626
TI  - [Physical exertion and congenital heart defects].

PMID- 21850627
TI  - Epistaxis as the reason for premature discontinuation of clopidogrel after
      percutaneous coronary angioplasty with stent implantation.
AB  - BACKGROUND: Haemorrhagic complications, including epistaxis, are the main reason
      for discontinuation of antiplatelet therapy in patients after stent implantation
      which increases risk of in-stent thrombosis. AIM: To evaluate the incidence of
      bleeding complications leading to premature discontinuation of antiplatelet
      therapy in patients after percutaneous coronary intervention (PCI) with stent
      implantation. METHODS: A total of 3250 patients (males 64%, mean age 62 +/- 10
      years) after PCI with stent implantation and without indications for chronic
      anticoagulation or the use of low molecular weight heparin participated in the
      survey. RESULTS: Antiplatelet therapy after discharge from hospital was continued
      by 98.5% of patients. Antiplatelet therapy, according to the current standards
      (clopidogrel with acetylsalicylic acid [ASA]), was used by 86.3% of the
      respondents and 8.4% of patients used clopidogrel without ASA. A 90.0% of
      patients after bare metal stent (BMS) implantation and 94.9% after drug-eluting
      stent (DES) implantation (p < 0.001) continued clopidogrel therapy for more than
      a month. The 12-month period of clopidogrel treatment was completed by 52.4% of
      patients after BMS implantation and by 68.9% after DES implantation (p < 0.001).
      Epistaxis occurred in 6.2% of patients. The incidence of epistaxis was similar in
      patients taking clopidogrel (4.7%) or ASA (4.6%) alone and in patients taking
      both drugs (5.8%). Episodes of epistaxis generally did not occur during the first
      month of antiplatelet therapy after DES implantation and were followed by
      discontinuation of clopidogrel therapy by 20.9% of patients with this bleeding
      complication. Factors favouring the occurrence of epistaxis included hypertension
      (OR = 2.22), chronic kidney disease (OR = 2.85) and liver cirrhosis (OR = 2.53).
      Epistaxis occurred in 12.1% of the patients who prematurely discontinued
      clopidogrel (OR = 2.43). CONCLUSIONS: 1. The occurrence of epistaxis is followed
      by premature discontinuation of clopidogrel therapy by one fifth of patients
      after coronary angioplasty and DES implantation. 2. Nosebleeds are more common in
      subjects with hypertension, chronic kidney disease and liver cirrhosis.

PMID- 21850628
TI  - [Use of clopidogrel after PCI--why do patients quit?].

PMID- 21850629
TI  - Exudative pericarditis in a pregnant woman as the first sign of non-Hodgkin's
      lymphoma.
AB  - This case report presents a 25 year-old pregnant female diagnosed with exudative
      pericarditis which was the first sign of cardiac lymphoma. Such a manifestation
      of this disease is rare and it represents a significant diagnostic and
      therapeutic problem in pregnant women.

PMID- 21850630
TI  - Infective endocarditis caused by Erysipelothrix rhusiopathiae involving three
      native valves.
AB  - Human infection with Erysipelothrix rhusiopathiae is extremely rare and
      occupationally related. This paper presents for the first time a case of a 47
      year-old male with endocarditis involving three valves simultaneously.

PMID- 21850631
TI  - [Myocardial infarction without coronary arteries stenoses in a patient with
      Jervell and Lange-Nielsen syndrome--diagnostic dilemmas].
AB  - According to the rules of differential diagnostics an acute coronary syndrome
      (ACS) often constitutes an initial diagnosis while a subsequent patient's follow
      up with troponin determination results in further verification of the diagnosis.
      A 55 year-old female with congenital hearing loss, poorly controlled
      hypertension, type 2 diabetes treated with oral medications, and hypothyreosis
      was admitted to the Department of Cardiology with 6 h long severe chest pain
      radiating over her back with concomitant dyspnea. She underwent urgent coronary
      angiography which showed no epicardial coronary narrowing. Acute heart failure
      symptoms occurred immediately after coronary angiography in the form of
      cardiogenic shock. Even though an ACS was diagnosed on the basis of typical
      biochemical, electrocardiographic and clinical criteria, a further follow-up
      suggested a possibility of a co-existance of other diseases which occurred to be
      a Jervell and Lange-Nielsen syndrome.

PMID- 21850633
TI  - [Is the regression of atherosclerosis only possible by lowering LDL levels and is
      this sufficient to reduce the tendency of these lipoproteins to oxidative
      modification?].
AB  - The process of atherogenesis can be conditioned by the imbalance between the
      tendency to oxidative modification of the lipoproteins containing apoprotein B100
      and antioxidant plasma properties. The paper discusses the situations leading to
      disruption of oxidative homeostasis on the basis of available data.

PMID- 21850634
TI  - [Psychocardiology--introduction to a new scientific discipline].

PMID- 21850635
TI  - [Giant ST segment elevation in electrocardiogram of a three year-old boy with
      brain oedema].
AB  - We present dramatic case of a 3 year-old boy who lost consciousness three weeks
      post Varicella Zoster virus infection. Cerebral edema was diagnosed with severe
      respiratory problems. Electrocardiogram showed transient but giant ST segment
      elevation, possibly secondary to brain damage.

PMID- 21850637
TI  - [Echocardiography as a first diagnostic step in kidney tumours].
AB  - Intracardiac tumours are usually found after clinical symptoms lead to a positive
      imaging study, or as an incidental finding of imaging study, usually
      echocardiography. Cardiac tumours range from non-neoplastic lesions to high grade
      malignancies. The majority of primary cardiac tumours are myxomas (in 75% cases)
      or sarcomas (about 10% cases). In this paper we present cases of 2 patients with
      right atrial tumour, extending from renal carcinoma, invading renal vein and
      inferior vena cava into right atrium. Two different therapeutic strategies were
      undertaken in those patients.

PMID- 21850638
TI  - [Rotational atherectomy in a patient with non-ST elevation acute coronary
      syndrome].
AB  - Rotational atherectomy is a valuable technique complementary to PCI in complex
      calcified coronary artery stenoses. A case of a 65 year-old man with non-ST
      elevation acute myocardial infarction (NSTEMI) treated with PCI with rotational
      atherectomy followed by two drug eluting stents (DES) implantation is presented.

PMID- 21850640
TI  - Acute coronary syndrome due to bare metal stent fracture in the right coronary
      artery.
AB  - Stent fracture (SF) has been suggested to be an unusual cause of restenosis after
      drug eluting-stent implantation. However, angiographically visible SF after bare
      metal stent (BMS) implantation is extremely rare. We present a case of a 58 year
      old male patient who presented with unstable angina secondary to a SF of a BMS
      within two months of elective percutaneous coronary intervention for right
      coronary artery associated with a muscle bridge and atherosclerotic stenosis.

PMID- 21850642
TI  - [Radiofrequency ablation of electrical storm using an epicardial approach in a
      patient with ischaemic cardiomyopathy].
AB  - We describe a case of a 63 year-old male who underwent successful RF ablation of
      recurrent ventricular tachycardia using epicardial approach.

PMID- 21850643
TI  - [Endo- or epicardial? How to reach the arrhythmia substrate?].

PMID- 21850644
TI  - [Not Available].

PMID- 21850645
TI  - [Not Available].

PMID- 21850646
TI  - [Thrombo-embolic pulmonary hypertension--do not spoil a chance for effective
      surgery!].
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary
      hypertension with persistent pulmonary perfusion defects causes by unresolved
      thrombi. All symptomatic CTEPH patients with documented pulmonary vascular
      resistance > 300 dyn*sec*cm(-5) and proximal lesions should be considered for
      surgical treatment--pulmonary endarterectomy. The role of pharmacological
      treatment remains controversial and should be restricted to inoperable cases and
      persistent pulmonary hypertension after pulmonary endarterectomy. Every year
      about 30 procedures is performed in two specialised centers in Poland with 1 year
      mortality at 8-9%. Number of procedures done gives the frequency of pulmonary
      endarterectomy at 0.7/million of population/year. Current data from UK indicate
      the actual ratio of surgical treatment of CTPH at 2/million/year. The article
      discusses reasons for CTEPH is underdiagnosed and why rate of surgical therapy in
      Poland is too low.

PMID- 21850647
TI  - Is performing balloon mitral valvotomy really safe without anticoagulation?

PMID- 21850648
TI  - High-resolution magic angle spinning NMR spectroscopy of human osteoarthritic
      cartilage.
AB  - Osteoarthritis (OA) is a degenerative disease of the joints and results in
      changes in the biochemical composition of cartilage. Previous studies have been
      undertaken that have used high-resolution NMR spectroscopy to study the
      biochemical composition of porcine, canine and bovine cartilage. In the present
      study, high-resolution magical angle spinning (HR-MAS) NMR spectroscopy at 11.7 T
      has been used to characterize metabolites and detect differences in the spectral
      signature of human knee articular cartilage from non-OA healthy cadaver knees and
      samples acquired from severe OA patients at the time of total knee replacement
      surgery. A statistically significant difference in the alanine (1.47 p.p.m.), N
      acetyl (2.04 p.p.m.), choline (3.25 p.p.m.) and glycine (3.55 p.p.m.) metabolite
      levels was observed between healthy and OA specimens. The results of the present
      study indicate that a decrease in the intensity of N-acetyl resonance occurs in
      the later stages of OA. A positive correlation of the N-acetyl levels as measured
      by (1)H HR-MAS NMR spectroscopy with the total proteoglycan content in the same
      cartilage specimens as measured by the glycosaminoglycan (GAG) assay was
      observed. This indicates that N-acetyl can serve as an important bio-marker of OA
      disease progression. A decrease in the alanine concentration in OA may be
      attributed to the degradation of the collagen framework with disease progression
      and eventual loss of the degradation products that are transported from cartilage
      into the synovial cavity.

PMID- 21850651
TI  - Recent Workshops of the HUPO Human Plasma Proteome Project (HPPP): a bridge with
      the HUPO CardioVascular Initiative and the emergence of SRM targeted proteomics.
AB  - We hereby provide a two-year update on the HUPO Human Plasma Proteome Project
      (HPPP) informed by advances presented at the HPPP sessions at the HUPO World
      Congresses in Toronto in September 2009 and in Sydney in September 2010.

PMID- 21850652
TI  - Probing the nanoscale phase separation and photophysics properties of low-bandgap
      polymer:fullerene blend film by near-field spectroscopic mapping.
AB  - The effect of the additive 1,8-octanedithiol (ODT) on the nanometer-scale
      morphology and local photophysical properties of low-bandgap polymer blends of
      poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b'] dithiophene)- alt
      4,7(2,1,3-benzothiadiazole)] (PCPDTBT) and [6,6]-phenyl C(61) -butyric acid
      methyl ester (PCBM) is investigated. Phase separations of the PCPDTBT:PCBM blend
      film induced by ODT are visualized by the morphological changes from fibril
      shaped features to spherical bumps, by the dramatically increased
      photoluminescence emission from PCPDTBT that was originally largely quenched, and
      by the fluctuations of spectral features at different locations of the sample
      surface. The correlations between the morphology and the local photophysical
      properties of the blend film with/without ODT at both the micrometer and
      nanometer scales are revealed by confocal and high-resolution near-field
      spectroscopic mapping techniques.

PMID- 21850654
TI  - A spatial scan statistic for nonisotropic two-level risk cluster.
AB  - Spatial scan statistic methods are commonly used for geographical disease
      surveillance and cluster detection. The standard spatial scan statistic does not
      model any variability in the underlying risks of subregions belonging to a
      detected cluster. For a multilevel risk cluster, the isotonic spatial scan
      statistic could model a centralized high-risk kernel in the cluster. Because
      variations in disease risks are anisotropic owing to different social,
      economical, or transport factors, the real high-risk kernel will not necessarily
      take the central place in a whole cluster area. We propose a spatial scan
      statistic for a nonisotropic two-level risk cluster, which could be used to
      detect a whole cluster and a noncentralized high-risk kernel within the cluster
      simultaneously. The performance of the three methods was evaluated through an
      intensive simulation study. Our proposed nonisotropic two-level method showed
      better power and geographical precision with two-level risk cluster scenarios,
      especially for a noncentralized high-risk kernel. Our proposed method is
      illustrated using the hand-foot-mouth disease data in Pingdu City, Shandong,
      China in May 2009, compared with two other methods. In this practical study, the
      nonisotropic two-level method is the only way to precisely detect a high-risk
      area in a detected whole cluster.

PMID- 21850653
TI  - Assessment of subchondral bone marrow lipids in healthy controls and mild
      osteoarthritis patients at 3T.
AB  - The compartment-specific lipid changes in femoral-tibial bone of healthy controls
      and mild osteoarthritis (OA) patients were quantified at 3.0 T. Healthy
      volunteers [Kellgren-Lawrence (KL) grade = 0; n = 15, 4 females, 11 males, mean
      age 39 +/- 16 years, age range = 24-78 years] and mild OA patients (KL = 1, 2; n
      = 26, 12 females, 14 males, mean age 61 +/- 14 years, age range = 27-80 years)
      were scanned on a 3 T scanner. Clinical proton density (PD)-weighted fast spin
      echo (FSE) images in the sagittal (without fat-saturation), axial and coronal
      (fat-saturation) planes were acquired for cartilage Whole-Organ MR Imaging Score
      (WORMS) grading. A voxel of 10 * 10 * 10 mm(3) was positioned in the medial and
      lateral compartments of the tibia [medial tibial (MT) and lateral tibial (LT)]
      and femur [medial femoral (MF) and lateral femoral (LF)] for MRS measurements
      using the single voxel-stimulated echo acquisition mode (STEAM) pulse sequence.
      All MRS data were processed with Java-based Magnetic Resonance User Interface
      (JMRUI). Wilcoxon's rank sum test and mixed model two-way analysis of variance
      (ANOVA) were performed to determine significant differences between different
      compartments as well as examine the effect of OA grade and compartment, and their
      interactions. Generally, the MF compartment index of unsaturation was increased
      in healthy subjects compared with OA subjects (whether graded by KL or WORMS
      score). Differences between MF at KL0 and all other compartments at KL1 except LF
      approached statistical significance (p < 0.05). Differences in saturated lipids
      signals could be observed predominantly in the 2.03 p.p.m. frequency shift.
      Healthy controls in the MF compartment had the lowest saturated lipid signals,
      and mild OA patients with KL2 and WORMS5-6 in the MF compartment had the highest
      saturated lipid signals compared with other compartments at 2.03 p.p.m. (p <
      0.05).

PMID- 21850656
TI  - Two founder mutations in the SEC23B gene account for the relatively high
      frequency of CDA II in the Italian population.
AB  - Congenital Dyserythropoietic Anemia type II is an autosomal recessive disorder
      characterized by unique abnormalities in the differentiation of cells of the
      erythroid lineage. The vast majority of CDA II cases result from mutations in the
      SEC23B gene. To date, 53 different causative mutations have been reported in 86
      unrelated cases (from the CDA II European Registry), 47 of them Italian. We have
      now identified SEC23B mutations in 23 additional patients, 17 Italians and 6 non
      Italian Europeans. The relative allelic frequency of the mutations was then
      reassessed in a total of 64 Italian and 45 non-Italian unrelated patients. Two
      mutations, E109K and R14W, account for over one-half of the cases of CDA II in
      Italy. Whereas the relative frequency of E109K is similar in Italy and in the
      rest of Europe (and is also prevalent in Moroccan Jews), the relative frequency
      of R14W is significantly higher in Italy (26.3% vs. 10.7%). By haplotype analysis
      we demonstrated that both are founder mutations in the Italian population. By
      using the DMLE+ program our estimate for the age of the E109K mutation in Italian
      population is ~2,200 years; whereas for the R14W mutation it is ~3,000 years. We
      hypothesize that E109K may have originated in the Middle East and may have spread
      in the heyday of the Roman Empire. Instead, R14W may have originated in Southern
      Italy. The relatively high frequency of the R14W mutation may account for the
      known increased prevalence of CDA II in Italy.

PMID- 21850658
TI  - High-dose (40,000 IU twice/week) alpha recombinant human erythropoietin as single
      agent in low/intermediate risk myelodysplastic syndromes: a retrospective
      investigation on 133 patients treated in a single institution.
AB  - We investigated the efficacy of alpha recombinant human erythropoietin (alpha
      rHuEPO) administered as single agent to 133 patients affected by myelodysplastic
      syndromes referring to our Institution in the last 10 years. WPSS score was "very
      low" in 67%, "low" in 19%, "intermediate" in 14%. The starting schedule was:
      40,000 IU bi-weekly, with reduction or suspension, when necessary, in responsive
      patients. According to new IWG criteria, response rate (RR) was 75%, 66%, 59%
      after 8, 16, 24 weeks, respectively. Comparing "very low" and "low/intermediate"
      risk, RR was 81% vs. 43% (P < 0.001); 70% vs. 45% (P = 0.040); 63% vs. 42% (P =
      NS) after 8, 16, 24 weeks. RR was significantly influenced by transfusion
      dependence (P = 0.039) and basal serum EPO level (P < 0.001). Mean Hb value was
      94 +/- 11 g/l before therapy; 114 +/- 19 after 8 weeks (P < 0.001); 116 +/- 18
      after 16 weeks (P < 0.001); 114 +/- 17 after 24 weeks (P < 0.001). Reduction or
      suspension of therapy significantly affected Hb level after 4 (P < 0.001) and 8
      weeks (P < 0.01). Conversely, restart of full dosage significantly enhanced again
      Hb level after 4 (P < 0.01) and 8 weeks (P < 0.001). 65% patients are alive (mean
      survival: 74 weeks). Seventy percent are alive in the "very low risk" group and
      38% in "low/intermediate risk" group (P < 0.001). Overall mean follow-up was 69
      weeks (range, 8-376): it was 80 weeks in responsive patients (max 376) and 38
      weeks in patients who progressively became unresponsive (max 168) (P < 0.01).
      Median response was 36 weeks, with 33% of patients still responding after one
      year. Treatment was well tolerated.

PMID- 21850657
TI  - Systemic infections mimicking thrombotic thrombocytopenic purpura.
AB  - The absence of specific diagnostic criteria, the urgency to begin plasma exchange
      treatment, and the risk for complications from plasma exchange make the initial
      evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP)
      difficult. Systemic infections may mimic the presenting clinical features of TTP.
      In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989-2010, 415
      consecutive patients have been clinically diagnosed with their first episode of
      TTP; in 31 (7%) the presenting clinical features were subsequently attributed to
      a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%)
      had the complete "pentad" of microangiopathic hemolytic anemia, thrombocytopenia,
      neurologic abnormalities, renal failure, and fever. Four (16%) of 25 patients who
      had ADAMTS13 measurements had <10% activity; three patients had a demonstrable
      ADAMTS13 inhibitor. Compared with 62 patients with severe ADAMTS13 deficiency
      (<10%) who had no recognized alternative disorders, patients with systemic
      infections had more frequent fever, coma, renal failure, and the complete
      "pentad" of clinical features. Seventeen different infectious etiologies were
      documented. A systematic literature review identified 67 additional patients with
      a diagnosis of TTP or HUS and also a systemic infection. Among all 98 patients,
      infections with 41 different bacteria, viruses, and fungi were documented,
      suggesting that many different systemic infections may mimic the presenting
      clinical features of TTP. Initial plasma exchange treatment is appropriate in
      critically ill patients with diagnostic features of TTP, even if a systemic
      infection is suspected. Continuing evaluation to document a systemic infection is
      essential to determine the appropriateness of continued plasma exchange.

PMID- 21850659
TI  - Follicular lymphoma: 2011 update on diagnosis and management.
AB  - DISEASE OVERVIEW: Follicular lymphoma (FL) is generally an indolent B-cell
      lymphoproliferative disorder of transformed follicular center B cells. FL is
      characterized by diffuse lymphoadenopathy, bone marrow involvement, splenomegaly,
      and less commonly other extranodal sites of involvement. In general, cytopenias
      can occur but constitutional symptoms of fever, nightsweats, and weight loss are
      uncommon. DIAGNOSIS: Diagnosis is based on histology of preferably biopsy of a
      lymph node. Immunohistochemical staining is positive in virtually all cases for
      cell surface CD19, CD20, CD10 and monoclonal immunoglobulin, as well as
      cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have
      the characteristic t(14;18) translocation involving the IgH/bcl-2 genes. RISK
      STRATIFICATION: The Follicular Lymphoma International Prognostic Index prognostic
      model for FL uses five independent predictors of inferior survival: age > 60
      years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of
      involved nodal areas > 4. The presence of 0-1, 2, and >=3 adverse factors defines
      low, intermediate, and high-risk disease with median 10 year survivals in the pre
      rituximab era of approximately 71, 51, and 36 months, respectively. With the use
      of more modern therapies, specifically anti-CD20 monoclonal antibody, the outcome
      has improved. RISK-ADAPTED THERAPY: Observation continues to be adequate for
      asymptomatic patients with low bulk disease and no cytopenias. For patients
      needing therapy, most patients are treated with chemotherapy plus rituximab,
      which has improved response rates, duration of response, and overall survival.
      Randomized studies have shown additional benefit for maintenance rituximab both
      following chemotherapy-rituximab and single agent rituximab. Autologous stem cell
      transplantation has not shown a survival benefit in first remission patients.
      Stem cell transplantation (SCT) including both autologous and allogeneic SCT or
      experimental agent therapy is considered for recurrent disease.

PMID- 21850660
TI  - Increased prevalence of osteonecrosis of the femoral head in children and
      adolescents with sickle-cell disease.

PMID- 21850661
TI  - Changing patterns of splenectomy in transfusion-dependent thalassemia patients.

PMID- 21850663
TI  - Fate of perchlorate in a man-made reflecting pond following a fireworks display
      in Albany, New York, USA.
AB  - Perchlorate is a widespread contaminant in aquatic environments. Despite this,
      the aquatic environmental fate of perchlorate released from fireworks displays is
      not well known. In the present study, we examined the fate of perchlorate in man
      made reflecting ponds, from 2008 to 2010, following three fireworks displays in
      Albany, New York, USA. Immediately after the fireworks display, perchlorate in
      pond waters increased significantly, with concentrations from 30 to 1,480 times
      higher than the baseline values. Perchlorate concentrations in pond water
      increased from 0.11 ug/L to up to 519 ug/L, following the fireworks display in
      2008. Perchlorate concentrations in pond water decreased at a first-order kinetic
      degradation rate, with a mean k(obs) value of 0.026 d-1 and an average half-life
      of 29 d. The rate of perchlorate deposition into water bodies following fireworks
      displays was estimated to range from 670 to 2,620 g/ha. We also estimated the
      perchlorate ingestion rate by the inhalation of aerosols of pond water by people
      frequently near the ponds. The estimated daily intake of perchlorate through the
      ingestion of aerosols was 32% (226 ng/kg body wt), 13% (92 ng/kg body wt), and 6%
      (42 ng/kg body wt) of the U.S. Environmental Protection Agency's reference dose
      for infants, children, and adults, respectively.

PMID- 21850662
TI  - Chronic myeloid leukemia 2011: successes, challenges, and strategies--proceedings
      of the 5th annual BCR-ABL1 positive and BCR-ABL1 negative myeloproliferative
      neoplasms workshop.

PMID- 21850664
TI  - No evidence for a fundamental visual motion processing deficit in adolescents
      with autism spectrum disorders.
AB  - It has been suggested that atypicalities in low-level visual processing
      contribute to the expression and development of the unusual cognitive and
      behavioral profile seen in autism spectrum disorders (ASD). However, previous
      investigations have yielded mixed results. In the largest study of its kind (ASD
      n = 89; non-ASD = 52; mean age 15 years 6 months) and testing across the spectrum
      of IQ (range 52-133), we investigated performance on three measures of basic
      visual processing: motion coherence, form-from-motion and biological motion (BM).
      At the group level, we found no evidence of differences between the two groups on
      any of the tasks, suggesting that there is no fundamental visual motion
      processing deficit in individuals with an ASD, at least by adolescence. However,
      we identified a tail of individuals with ASD (18% of the sample) who had
      exceptionally poor BM processing abilities compared to the non-ASD group, and who
      were characterized by low IQ. For the entire sample of those both with and
      without ASD, performance on the BM task uniquely correlated with performance on
      the Frith-Happe animations, a higher-level task that demands the interpretation
      of moving, interacting agents in order to understand mental states. We
      hypothesize that this association reflects the shared social-cognitive
      characteristics of the two tasks, which have a common neural underpinning in the
      superior temporal sulcus.

PMID- 21850665
TI  - Methylprednisolone-loaded PLGA microspheres: a new formulation for sustained
      release via intra-articular administration. A comparison study with
      methylprednisolone acetate in rats.
AB  - Methylprednisolone (MP) released by poly(d,l-lactide-co-glycolide) microspheres
      (PLGA MS) was monitored in plasma after intra-articular (i.a.) administration
      into rat joint. A validated LC-ESI-MS/MS method was used to quantify the
      plasmatic concentrations of MP. The calculated pharmacokinetic parameters were
      compared to those obtained after the i.a. administration of a commercially
      available suspension of MP acetate (MPA). Different pharmacokinetic profiles were
      observed in the two formulations, and a lower peak level (C(max) = 13.7 +/- 4.3
      ng . mL(-1)) and AUC(0-72 h) (198 +/- 45 ng . mL(-1) . h) were observed for MP
      PLGA MS than MPA (C(max) = 18.4 +/- 2.7 ng . mL(-1)) and AUC(0-72 h) (943 +/- 249
      ng . mL(-1) . h). The administration of MP-PLGA MS resulted in a rapid increase
      in the MP concentration at 30 min, with a t(max) at 0.8 +/- 0.3 h. Instead, for
      the MPA suspension the t(max) was 32.0 +/- 13.9 h. These differences were
      indirectly confirmed by the evaluation of the extra-articular effects, namely,
      carrageenan-induced paw edema, since MP-PLGA MS showed a lower anti-inflammatory
      activity than MPA.

PMID- 21850666
TI  - Aerosol tribocharging and its relation to the deposition of OxisTM Turbuhaler(r)
      in the electrical next generation impactor.
AB  - Although there have been published electrostatic characterisation studies of drug
      only Turbuhaler(r) and lactose carrier-drug formulations, there has not been an
      investigation into spheronised agglomerates containing micronised lactose and
      eformoterol, such as in Oxis(r) Turbuhaler(r). Ten doses of Oxis(r) (12 u g
      eformoterol) were dispersed into an electrical next generation impactor (eNGI) in
      a single run, and runs were conducted in triplicate to determine the aerosol
      performance and aerosol charge distribution at flow rates of 30, 60 and 90 L/min.
      Eformoterol fine particle fraction (FPF) reached a maximum of 50%-60% at 60 and
      90 L/min, whereas lactose FPF increased from 31% to 42% when flow rate was
      increased from 30 to 90 L/min. Specific net charge (C/u g) within the eNGI stages
      increased from 30 to 60 L/min, but then decreased at 90 L/min. These results were
      attributed to the shift in balance between surface charging after interparticle
      and particle-surface collision (dominant at 30 and 60 L/min) and charge
      separation after impact fragmentation of agglomerates (dominant at 90 L/min).
      However, the aerosol charge profiles do not suggest that electrostatic forces
      play a major role in the deposition of Oxis(r) Turbuhaler(r) dry powder
      formulation.

PMID- 21850667
TI  - Non-integrating lentiviral vectors for specific killing of Epstein-Barr virus
      nuclear antigen 1-positive B cell lymphoma cells.
AB  - BACKGROUND: Epstein-Barr virus (EBV) causes a range of life-threatening B
      lymphocyte malignancies but, despite the use of various strategies, treatment
      remains problematic. METHODS: In the present study, we developed a non
      integrating lentiviral vector (NILV) that mediates specific killing of EBV
      nuclear antigen 1 (EBNA1)-expressing cells with minimal toxicity to EBNA1
      negative cells. The EBV family of repeats (FR) was cloned intok the NILV genome
      upstream of various transgenes. RESULTS: The presence of the FR in the NILV
      genome induced transcriptional up-regulation and prolonged the expression of a
      transgene specifically in EBNA1-positive B cells. Transgene expression from an FR
      containing NILV was also prolonged in EBV-transformed cells compared to an FR
      negative NILV. We found that the delivery of an FR-containing NILV encoding
      herpes simplex virus 1 thymidine kinase (TK) lead to the killing of more than 99%
      of EBNA1-positive B cells with minimal toxicity to EBNA1-negative cells in the
      presence of gancyclovir. EBNA1-positive cells were not killed by an FR-negative
      vector containing the TK gene. An FR-TK-containing NILV also specifically killed
      EBNA1-containing cells in a mixed population of EBNA1-positive and EBNA1-negative
      cells, thus confirming that NILV-FR-TK-mediated killing is specific for EBNA1
      expressing cells. CONCLUSIONS: Transgene expression from our NILVs is both EBNA1
      specific and dependent upon the presence of the FR. The results obtained in the
      present study indicate that NILVs have potential use in the treatment of EBV
      associated B cell malignancies.

PMID- 21850668
TI  - Regional alterations of brain microstructure in Parkinson's disease using
      diffusion tensor imaging.
AB  - This study tested the hypothesis that diffusion tensor imaging can detect
      alteration in microscopic integrity of white matter and basal ganglia regions
      known to be involved in Parkinson's disease (PD) pathology. It was also
      hypothesized that there is an association between diffusion abnormality and PD
      severity and subtype. Diffusion tensor imaging at 4 Tesla was obtained in 12 PD
      and 20 control subjects, and measures of fractional anisotropy and mean
      diffusivity were evaluated using both region-of-interest and voxel-based methods.
      Movement deficits and subtypes in PD subjects were assessed using the Motor
      Subscale (Part III) of the Unified Parkinson's Disease Rating Scale. Reduced
      fractional anisotropy (P < .05, corrected) was found in PD subjects in regions
      related to the precentral gyrus, substantia nigra, putamen, posterior striatum,
      frontal lobe, and the supplementary motor areas. Reduced fractional anisotropy in
      the substantia nigra correlated (P < .05, corrected) with the increased rating
      scale motor scores. Significant spatial correlations between fractional
      anisotropy alterations in the putamen and other PD-affected regions were also
      found in the context of PD subtypes index analysis. Our data suggest that
      microstructural alterations detected with diffusion tensor might serve as a
      potential biomarker for PD.

PMID- 21850670
TI  - Ocular pharmacokinetics of a novel tetrahydroquinoline analog in rabbit:
      absorption, disposition, and non-compartmental analysis.
AB  - The pharmacologically active compound (33% reduction in rabbit intraocular
      pressure recovery rate assay) 1-ethyl-6-fluoro-1,2,3,4-tetrahydroquinoline (MC4),
      which showed ocular hypotensive action and had optimum physicochemical
      properties, was characterized for its ocular absorption and distribution
      properties to better understand its in vivo potency in comparison with an
      inactive compound, N-ethyl-1,4-benzoxazine (MC1). Tissue distribution to various
      ocular tissues was determined after absorption by both corneal and conjunctival
      scleral routes, following administration by the "topical infusion" technique. The
      rank order of penetration for both the compounds was cornea > iris-ciliary body >
      aqueous humor > lens > conjunctiva-sclera. Overall, MC4 had significantly higher
      concentrations than MC1 in various ocular tissues, but particularly in the iris
      ciliary body, which is the site of action (biophase). Ocular disposition studies
      of the active compound MC4 were then conducted to characterize its elimination
      kinetics, and the pharmacokinetic parameters were determined by non-compartmental
      and moment analysis using equations specific to "topical infusion" technique:
      first-order absorption rate constant, 4.1 * 10(-4) min(-1) ; elimination rate
      constant, 0.012 min(-1) ; mean residence time, 39.6 min; steady-state volume of
      distribution, 0.721 mL; and aqueous humor ocular clearance, 8.44 uL/min. The
      results were consistent with the conclusion that MC4 is well absorbed and
      distributed to the active site.

PMID- 21850671
TI  - Computational fluid dynamics modeling of mass-transfer behavior in a bioreactor
      for hairy root culture. II. Analysis of ultrasound-intensified process.
AB  - Recently, cichoric acid production from hairy roots of Echinacea purpurea was
      significantly improved by ultrasound stimulation in an airlift bioreactor. In
      this article, the possible mechanism on ultrasound-intensified hairy root culture
      of E. purpurea in the bioreactor was elucidated with the help of computational
      fluid dynamics (CFD) simulation, membrane permeability detection, dissolved
      oxygen concentration detection, confocal laser-scanning microscopy (LSM)
      observation, and phenylalanine ammonium lyase (PAL) activity analysis. The CFD
      model developed in Part I was used to simulate the hydrodynamics and oxygen mass
      transfer in hairy root bioreactor culture stimulated by ultrasound. A dynamic
      mesh model combined with a changing Schmidt number method was used for the
      simulation of the ultrasound field. Simulation results and experimental data
      illustrated that ultrasound intensified oxygen mass transfer in the hairy root
      clump, which subsequently stimulated root growth and cichoric acid biosynthesis.
      Ultrasound increased the hairy root membrane permeability, and a high root
      membrane permeability of 0.359 h(-1) was observed at the bottom region in the
      bioreactor. LSM observation showed that the change in the membrane permeability
      recovered to normal in the further culture after ultrasound stimulation. PAL
      activity in the hairy roots was stimulated by ultrasound increase and was
      correlated well to cichoric acid accumulation in the hairy roots of E. purpurea.

PMID- 21850672
TI  - Perlecan domain V modulates astrogliosis in vitro and after focal cerebral
      ischemia through multiple receptors and increased nerve growth factor release.
AB  - Astrogliosis constitutes part of the central nervous system's physiological
      response to injury. Considered for decades to be a major challenge for brain
      repair, recent studies have highlighted it as a promoter of such repair
      mechanisms. Recently, our group demonstrated the ability of perlecan domain V
      (DV) to be a novel potential stroke therapy by its neuroprotective effects.
      However, the potential for DV to modulate astrogliosis has not been investigated.
      The aim of this study is to better understand the relevance of DV to astrogliosis
      using both in vitro and in vivo rodent models. Notably, under basal conditions,
      astrocytes express all three DV receptors described in the literature: integrin
      alpha2beta1, alpha5beta1, and alpha-dystroglycan (alphaDG). DV promoted astrocyte
      cell adhesion, cell migration as well as astrocyte stellation. Moreover, DV
      induced nerve growth factor (NGF) secretion through a alphaDG- and ERK-dependent
      pathway. In contrast, alpha2beta1 or alpha5beta1 mediated DV antiproliferative
      effects in astrocytes. NGF production after DV treatment acted as a strong anti
      proliferative agent. Another remarkable effect of DV was that it decreased
      several markers of astrogliosis such as glial fibrillary acidic protein (GFAP),
      neurocan and phosphacan both in vitro and in vivo, suggesting the role of DV as a
      potential modulator of postinjury during late astrogliosis, and eventually the
      onset of glial scarring. Taken together, our study demonstrates the ability of DV
      to modulate key events of astrogliosis by promoting early astrogliosis and
      inhibiting glial scar formation, suggesting an additional therapeutic benefit of
      DV for recovery from stroke. (c) 2011 Wiley-Liss, Inc.

PMID- 21850673
TI  - Analysis of carbohydrates and glycoconjugates by matrix-assisted laser
      desorption/ionization mass spectrometry: an update for 2007-2008.
AB  - This review is the fifth update of the original review, published in 1999, on the
      application of MALDI mass spectrometry to the analysis of carbohydrates and
      glycoconjugates and brings coverage of the literature to the end of 2008. The
      first section of the review covers fundamental studies, fragmentation of
      carbohydrate ions, use of derivatives and new software developments for analysis
      of carbohydrate spectra. Among newer areas of method development are glycan
      arrays, MALDI imaging and the use of ion mobility spectrometry. The second
      section of the review discusses applications of MALDI MS to the analysis of
      different types of carbohydrate. Specific compound classes that are covered
      include carbohydrate polymers from plants, N- and O-linked glycans from
      glycoproteins, biopharmaceuticals, glycated proteins, glycolipids, glycosides and
      various other natural products. There is a short section on the use of MALDI mass
      spectrometry for the study of enzymes involved in glycan processing and a section
      on the use of MALDI MS to monitor products of the chemical synthesis of
      carbohydrates with emphasis on carbohydrate-protein complexes and
      glycodendrimers. Corresponding analyses by electrospray ionization now appear to
      outnumber those performed by MALDI and the amount of literature makes a
      comprehensive review on this technique impractical. However, most of the work
      relating to sample preparation and glycan synthesis is equally relevant to
      electrospray and, consequently, those proposing analyses by electrospray should
      also find material in this review of interest.

PMID- 21850674
TI  - Acquired factor XI deficiency in a child with membranoproliferative
      glomerulonephritis.
AB  - We describe a 7-year-old male with membranoproliferative glomerulonephritis who
      presented with nephrotic syndrome and subsequently developed factor XI (fXI)
      deficiency. An association between these conditions has not been described
      previously. In this case, fXI deficiency was caused by an antibody to fXI that
      enhanced clearance of the protein from plasma. Loss of fXI in the urine did not
      appear to be involved. Antibody-mediated clearance of prothrombin or factor X can
      cause acquired deficiencies of these proteins. This is the first report, to our
      knowledge, of an antibody that causes fXI deficiency by this mechanism.

PMID- 21850675
TI  - Preclinical evaluation of pemetrexed in pediatric solid tumors.
AB  - Renewed interest in antifols for the treatment of childhood cancers has resulted
      from identification of novel antifols with broad spectrums of anti-cancer
      activity. We evaluated the in vitro cytotoxicity of methotrexate and pemetrexed
      in a panel of 12 pediatric solid tumor cell lines using the sulforhodamine-B
      assay. The Ewing sarcoma (ES) cell lines demonstrated the greatest sensitivity to
      both methotrexate and pemetrexed. Expression of folate pathway genes (DHFR, TS,
      GARFT, GGH) did not correlate with in vitro drug sensitivity. Further evaluation
      of pemetrexed for the treatment of ES is warranted.

PMID- 21850676
TI  - Treatment of nephroblastoma in Africa: results of the first French African
      pediatric oncology group (GFAOP) study.
AB  - BACKGROUND: The multidisciplinary management of nephroblastoma has been defined
      through multicentric prospective studies and an average 90% of patients cured
      expected. In Africa, such studies are uncommon and results are fragmentary or
      unknown in most of the countries. We report the results of the GFAOPNEPHRO 01
      study using SIOP 2001 protocol approach. PROCEDURE: From April 1, 2001 to March
      31, 2004, 8 African Pilot Units were selected to participate in a nonrandomized
      prospective study. All patients referred with a clinical and radiological
      diagnosis of nephroblastoma were registered, those aged over 6 months and less
      than 18 years with a unilateral tumor not previously treated were included in
      this study and received preoperative chemotherapy. Patients with unfavorable
      histology or with a tumor other than Wilms tumor, and those with stage IV tumor
      and persistent disease after surgery were secondarily excluded. RESULTS: Of the
      229 patients initially registered, 166 were included and finally 133 retained in
      the study, after surgery. Tumor rupture occurred in 7.5% of the patients. Thirty
      five percent were stage I, 22% stage II, 23% stage III, and 18% stage IV. Two
      year disease-free survival and 5-year survival are, respectively: 77.9% and 76.7%
      for localized tumors, 72.7% and 71.6% for all study patients. CONCLUSIONS: It is
      possible to conduct African multicentric therapeutic studies within the framework
      of GFAOP. Results in terms of event-free survival and survival are satisfactory.
      Improvements with respect to procedure, data collection, and outcome are expected
      in a new study.

PMID- 21850677
TI  - Hereditary cancer risk assessment in a pediatric oncology follow-up clinic.
AB  - BACKGROUND: Pediatric cancer survivors are at risk for multiple late effects
      including second malignancies, some a direct consequence of genetic
      susceptibility. Appropriate surveillance and management for the survivor and at
      risk family members can often be established if the genetic predisposition is
      recognized and/or diagnosed. Numerous published guidelines outline which adult
      cancer patients and survivors should be referred for hereditary cancer risk
      assessment. In the pediatric oncology setting, minimal guidance exists for
      healthcare providers to determine which patients and families to refer for
      genetic evaluation. PROCEDURE: The aim of this project was to determine what
      percentage of childhood cancer survivors are appropriate for further evaluation
      in a hereditary cancer program or genetics clinic and characterize indications
      for referral. Participants included pediatric cancer survivors seen for follow-up
      in a large cancer survivor center. Medical and family histories were obtained and
      reviewed by a certified genetic counselor at the survivor's annual visit.
      Eligibility for genetics referral was determined based on personal/family medical
      history and published literature. RESULTS: Of 370 survivors of childhood cancer,
      109 (29%) were considered eligible for genetics follow-up or referral. Family
      history of cancer is the most prevalent reason identified for eligibility for
      further genetics evaluation (61%) followed by tumor type (18%), medical history
      (16%), and family history of another condition (6%). CONCLUSIONS: This project
      provides evidence that inclusion of genetic evaluation is feasible and relevant
      in the care of childhood cancer survivors. Further study is warranted to
      determine optimal timing and clinical utility of this multidisciplinary and
      family-centered approach.

PMID- 21850678
TI  - Tissue Doppler evaluation of systolic and diastolic cardiac functions in long
      term survivors of Hodgkin lymphoma.
AB  - BACKGROUND: Monitoring for late adverse events is crucial in long-term management
      of childhood cancer survivors. A case-control study to evaluate long-term
      cardiovascular status of childhood Hodgkin lymphoma (HL) using tissue Doppler
      imaging (TDI) was performed. PATIENTS AND METHODS: Patients diagnosed with HL
      before age of 18 that completed therapy and were in remission and a control group
      of healthy children were evaluated by echocardiography and TDI. RESULTS: Total of
      72 HL survivors were included in the study. Median age at diagnosis, remission
      time, and age at time of echocardiography were 7 (2-16), 9 (2-20), and 17.5 (7
      27) years, respectively. TDI revealed decreased S' velocity, reflecting systolic
      dysfunction in HL survivors, at medial and lateral mitral annuli and at middle
      segment of interventricular septum (IVS; P < 0.01) for all. Moreover, TDI showed
      decreased peak E' velocity at medial mitral annulus [12.4 cm/s (5.5-16.3) vs.
      13.3 cm/s (10.2-18.9), P = 0.03] and at middle segment of IVS [10 cm/s (5.3-16.3)
      vs. 11.6 cm/s (6.7-16.7), P < 0.01] and prolongation of isovolemic relaxation
      time at medial and lateral annuli of the mitral valve (P < 0.01) and at middle
      segment of IVS (P = 0.03) suggesting diastolic dysfunction in HL survivors.
      CONCLUSION: Cardiac dysfunction after childhood cancer therapy may develop after
      many years. Since systolic and diastolic dysfunction can be seen in these
      patients periodic echocardiographic screening of both systolic and diastolic
      function in the survivors of HL might be useful in the follow-up of these
      patients.

PMID- 21850679
TI  - Dietary intake after treatment in child cancer survivors.
AB  - BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of
      complications such as obesity, diabetes, and osteoporosis which have the
      potential to, in part, be controlled with dietary interventions. To allow the
      development of appropriate dietary interventions for younger cancer survivors
      data on their dietary intake as well as information on parental nutrition views
      and practices need to be assessed. PROCEDURE: Dietary intake of 50 CCS was
      assessed with a 3-day food diary (parent report). Parent child feeding practices
      were assessed with the Child Feeding Questionnaire (CFQ). Historical and
      anthropometric data was extracted from medical records. Survivors were less than
      13 years old and less than 5 years after treatment completion. RESULTS: Twenty
      percent of participating CCS was overweight or obese and 54% were consuming above
      their estimated energy requirements. Fifty, 32% and 44% of children did not meet
      requirements for folate, calcium, and iron respectively. There was a significant
      trend for increasing BMI percentiles from diagnosis to time of assessment (56.29
      vs. 67.17, P = 0.01). Results from the CFQ showed that parents were more likely
      to monitor (3.99) and use a restrictive form of parenting (3.43) to control their
      child's food intake rather than pressure their child to eat (2.77) (P = 0.001).
      CONCLUSION: This group displayed excessive energy intake (kilojoules) and poor
      dietary habits. Parents' restrictive feeding style may be contributing to these
      habits. Early interventions targeting the dietary intake of young survivors and
      associated parent feeding practices may prevent some of the deleterious long-term
      effects associated with childhood cancer therapy.

PMID- 21850680
TI  - Hot-topic debate on tolerance: immunosuppression withdrawal.
AB  - KEY POINTS: 1. Liver allografts exhibit intrinsic tolerogenic properties that
      result in their spontaneous acceptance in many experimental animal models. 2. In
      clinical transplantation, liver allografts require milder immunosuppression
      regimens than other organs, are relatively resistant to antibody-mediated
      rejection, and only very rarely are lost because of immunological insults. 3. A
      fraction of stable liver transplant recipients can withdraw from all
      immunosuppression therapy and then maintain normal graft function and not
      experience rejection. This phenomenon is known as spontaneous operational
      tolerance (SOT). 4. The intentional discontinuation of immunosuppression in
      stable liver transplant recipients has led to successful weaning in almost 20% of
      recipients, but the true prevalence of SOT in unselected recipients is still
      unknown. 5. The prevalence could be higher in pediatric recipients undergoing
      transplantation before 1 year of age and in adult recipients with more than 10
      years of posttransplant follow-up. 6. Rejection occurring during medically
      supervised immunosuppression weaning trials tends to be mild and, in the
      overwhelming majority of cases, can be easily resolved without the administration
      of high-dose immunosuppression. 7. Tolerant liver recipients exhibit specific
      transcriptional patterns in peripheral blood and liver tissue that may constitute
      future diagnostic markers of tolerance. 8. There is still no formal proof that
      the discontinuation of low-dose immunosuppression in long-term survivors of liver
      transplantation improves the morbidity and mortality rates associated with
      immunosuppression therapy.

PMID- 21850682
TI  - Life on the fringes - let's try it this way.

PMID- 21850684
TI  - Immunosuppression in pediatric liver transplantation: are little people
      different?
AB  - KEY POINTS: 1. Children differ from adults in the pharmacokinetics and dynamics
      of most immunosuppressive agents. 2. A lack of clinical trials continues to be an
      issue for newer agents. 3. On the basis of clinical case series, mycophenolate
      mofetil and sirolimus are increasingly being used as renal-sparing agents. 4. In
      comparison with adults, the recurrence of both viral hepatitis and hepatocellular
      carcinoma is less of an issue in children. 5. Particular attention should be paid
      to complete age-appropriate immunization to avoid vaccine-preventable diseases.
      6. Paying special attention to adherence and the transition to adult services is
      essential for minimizing graft loss.

PMID- 21850685
TI  - The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung
      cancer in Southern and Eastern Chinese populations.
AB  - Peptidyl-prolyl cis/trans isomerase (PPIase), PIN1, has been found to be a
      critical catalyst that involves in multiple oncogenic signaling pathways.
      Recently, several putative functional polymorphisms of the PIN1 gene have been
      identified to be associated with cancer risk. In this study, we tested the
      hypothesis that two common polymorphisms, c.-842G>C (rs2233678) and c.-667C>T
      (rs2233679), in the PIN1 promoter are associated with risk of lung cancer. In two
      independent case-control studies of 1,559 lung cancer cases and 1,679 controls
      conducted in Southern and Eastern Chinese population, we found that compared with
      the most common c.-842GG genotype, the carriers of c.-842C variant genotypes (GC
      + CC) had a decreased risk of lung cancer (odds ratio [OR] = 0.63, 95% confidence
      interval [CI] = 0.51-0.78, p = 1.13 * 10(-5) ). Although no association was
      observed between the c.-667C>T polymorphism and cancer risk, we found that the
      haplotype "C-C" had a greater protective effect (OR = 0.39, 95% CI = 0.23-0.67, p
      = 5.03 * 10(-4) ). The stratification analysis showed that the protective role of
      c.-842C variants was more pronounced in current smokers (p = 4.45 * 10(-5) ),
      especially in male smokers (p = 6.71 * 10(-6) ) and in those who smoked more than
      20 pack-years (p = 2.30 * 10(-5) ) and the c.-842C variant genotypes interacted
      with smoking status (P(interaction) = 0.019) or pack-years smoked (P(interaction)
      = 0.008) on reducing cancer risk. Further functional assay revealed that the c.
      842C variant allele had a lower transcription activity in luciferase assay and a
      lower DNA-binding ability with nuclear proteins, and low transcription activity
      in western blot assay. In conclusions, our data suggest that functional c.-842C
      variants and haplotype "C-C" in the PIN1 promoter contribute to decreased risk of
      lung cancer by diminishing the promoter activity, which may be susceptibility
      biomarkers for lung cancer.

PMID- 21850686
TI  - Extending the scope of diagnostic chromosome analysis: detection of single gene
      defects using high-resolution SNP microarrays.
AB  - Microarray analysis has provided significant advances in the diagnosis of
      conditions resulting from submicroscopic chromosome abnormalities. It has been
      recommended that array testing should be a "first tier" test in the evaluation of
      individuals with intellectual disability, developmental delay, congenital
      anomalies, and autism. The availability of arrays with increasingly high probe
      coverage and resolution has increased the detection of decreasingly small copy
      number changes (CNCs) down to the intragenic or even exon level. Importantly,
      arrays that genotype SNPs also detect extended regions of homozygosity. We
      describe 14 examples of single gene disorders caused by intragenic changes from a
      consecutive set of 6,500 tests using high-resolution SNP microarrays. These cases
      illustrate the increased scope of cytogenetic testing beyond dominant chromosome
      rearrangements that typically contain many genes. Nine of the cases confirmed the
      clinical diagnosis, that is, followed a "phenotype to genotype" approach. Five
      were diagnosed by the laboratory analysis in the absence of a specific clinical
      diagnosis, that is, followed a "genotype to phenotype" approach. Two were
      clinically significant, incidental findings. The importance of astute clinical
      assessment and laboratory-clinician consultation is emphasized to optimize the
      value of microarrays in the diagnosis of disorders caused by single gene copy
      number and sequence mutations.

PMID- 21850687
TI  - Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating
      oxidative stress-induced neuronal death.
AB  - Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are responsible for
      autosomal dominant and sporadic Parkinson disease (PD), possibly exerting their
      effects via a toxic gain of function. A common p.G2019S mutation (rs34637584:A>G)
      is responsible for up to 30-40% of PD cases in some ethnic populations. Here, we
      show that LRRK2 interacts with human peroxiredoxin 3 (PRDX3), a mitochondrial
      member of the antioxidant family of thioredoxin (Trx) peroxidases. Importantly,
      mutations in the LRRK2 kinase domain significantly increased phosphorylation of
      PRDX3 compared to wild-type. The increase in PRDX3 phosphorylation was associated
      with decreased peroxidase activity and increased death in LRRK2-expressing but
      not in LRRK2-depleted or vector-transfected neuronal cells. LRRK2 mutants
      stimulated mitochondrial factors involved in apoptosis and induced production of
      reactive oxygen species (ROS) and oxidative modification of macromolecules.
      Furthermore, immunoblot and immunohistochemical analysis of postmortem human PD
      patients carrying the p.G2019S mutation showed a marked increase in
      phosphorylated PRDX3 (p-PRDX3) relative to normal brain. We showed that LRRK2
      mutations increase the inhibition of an endogenous peroxidase by phosphorylation
      promoting dysregulation of mitochondrial function and oxidative damage. Our
      findings provide a mechanistic link between the enhanced kinase activity of PD
      linked LRRK2 and neuronal cell death.

PMID- 21850688
TI  - Living donor hepatectomy: the importance of the residual liver volume.
AB  - Living liver donation is a successful treatment for patients with end-stage liver
      disease. Most adults are provided with a right lobe graft to ensure a generous
      recipient liver volume. Some centers are re-exploring the use of smaller left
      lobe grafts to potentially reduce the donor risk. However, the evidence showing
      that the donor risk is lower with left lobe donation is inconsistent, and most
      previous studies have been limited by potential learning curve effects, small
      sample sizes, or poorly matched comparison groups. To address these deficiencies,
      we conducted a case-control study. Forty-five consecutive patients who underwent
      left hepatectomy (LH; n = 4) or left lateral segmentectomy (LLS; n = 41) were
      compared with matched controls who underwent right hepatectomy (RH) or extended
      right hepatectomy (ERH). The overall complication rates of the 3 groups were
      similar (31%-37%). There were no grade 4 or 5 complications. There were more
      grade 3 complications for the RH patients (13.3%) and the ERH patients (15.6%)
      versus the LH/LLS patients (2.2%). The extent of the liver resection
      significantly correlated with the peak international normalized ratio (INR), the
      days to INR normalization, and the peak bilirubin level. A univariate analysis
      demonstrated that hepatectomy, the spared volume percentage, and the peak
      bilirubin level were strongly associated with grade 3 complications. A higher
      peak bilirubin level, which correlated with a lower residual liver volume, was
      associated with grade 3 complications in a multivariate analysis (P = 0.005). RH
      and grade 3 complications were associated with an increased length of stay (>7
      days) in a multivariate analysis. In conclusion, this analysis demonstrates a
      significant correlation between the residual liver volume and liver dysfunction,
      serious adverse postoperative events, and longer hospital stays. Donor safety
      should be the first priority of all living liver donor programs. We propose that
      the surgical procedure removing the smallest amount of the liver required to
      provide adequate recipient graft function should become the standard of care for
      living liver donation.

PMID- 21850689
TI  - Computed tomography liver volumetry using 3-dimensional image data in living
      donor liver transplantation: effects of the slice thickness on the volume
      calculation.
AB  - The purpose of this study was to evaluate the relationship between the slice
      thickness and the calculated volume in computed tomography (CT) liver volumetry
      through the comparison of the results from images [including 3-dimensional (3D)
      images] with various slice thicknesses. Twenty potential adult liver donors (12
      men and 8 women) with a mean age of 39 years (range = 24-64 years) underwent CT
      with a 64-section multidetector row CT scanner after the intravenous injection of
      a contrast material. Four image sets with slice thicknesses of 0.625, 2.5, 5, and
      10 mm were used. First, a program developed in our laboratory for automated liver
      extraction was applied to the CT images, and the liver boundaries were determined
      automatically. Then, an abdominal radiologist reviewed all images onto which
      automatically extracted boundaries had been superimposed and then edited the
      boundaries on each slice to enhance the accuracy. The liver volumes were
      determined via the counting of the voxels within the liver boundaries. The mean
      whole liver volumes estimated with CT were 1322.5 cm(3) from 0.625-mm images,
      1313.3 cm(3) from 2.5-mm images, 1310.3 cm(3) from 5-mm images, and 1268.2 cm(3)
      from 10-mm images. The volumes calculated from 3D (0.625-mm) images were
      significantly larger than the volumes calculated from thicker images (P < 0.001).
      The partial liver volumes of right lobes, left lobes, and lateral segments were
      evaluated in a similar manner. The estimated maximum difference in the calculated
      volumes of lateral segments was -10.9 cm(3) (-4.63%) between 0.625- and 5-mm
      images. In conclusion, liver volumes calculated from 2.5-mm-thick or thicker
      images are significantly smaller than liver volumes calculated from 3D images. If
      a maximum error of 5% in the calculated graft volume will not have a significant
      clinical impact, 5-mm-thick images are acceptable for CT volumetry. If the impact
      is significant, 3D images could be essential.

PMID- 21850690
TI  - A randomized, multicenter study comparing steroid-free immunosuppression and
      standard immunosuppression for liver transplant recipients with chronic hepatitis
      C.
AB  - This randomized, prospective, multicenter trial compared the safety and efficacy
      of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard
      IS regimens in patients undergoing transplantation for hepatitis C virus (HCV)
      infection. The outcome measures were acute cellular rejection (ACR), severe HCV
      recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus
      (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and
      corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no
      corticosteroids (arm 3; n = 146). In all, 295 HCV RNA-positive subjects were
      enrolled. At 2 years, there were no differences in ACR, HCV recurrence
      (biochemical evidence), patient survival, or graft survival rates. The side
      effects of IS did not differ, although there was a trend toward less diabetes in
      the steroid-free group. Liver biopsy samples revealed no significant differences
      in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence
      (ie, an inflammation grade >= 3 and/or a fibrosis stage >= 2) in years 1 (48.2%,
      50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively).
      Although we have found that steroid-free IS is safe and effective for liver
      transplant recipients with chronic HCV, steroid sparing has no clear advantage in
      comparison with traditional IS.

PMID- 21850692
TI  - Patients with non-[18 F]fludeoxyglucose-avid advanced hepatocellular carcinoma on
      clinical staging may achieve long-term recurrence-free survival after liver
      transplantation.
AB  - There is increasing evidence that a relevant number of patients with
      hepatocellular carcinoma (HCC) exceeding the Milan criteria may benefit from
      liver transplantation (LT). We retrospectively analyzed the prognostic
      significance of [(18) F]fludeoxyglucose ([(18) F]FDG) positron emission
      tomography (PET) for identifying appropriate LT candidates with advanced HCC on
      clinical staging. Between 1995 and 2008, 111 patients with HCC were listed for
      LT. All underwent a pretransplant PET evaluation. LT was performed for 91 of
      these patients. The tumor recurrence rate after LT was 3.6% for patients with non
      [(18) F]FDG-avid (PET(-) ) tumors, but it was 54.3% for patients with [(18) F]FDG
      avid (PET(+) ) tumors (P < 0.001). The 5-year recurrence-free survival rates were
      comparable for patients with tumors meeting the Milan criteria (86.2%) and
      patients with PET(-) HCC exceeding the Milan criteria (81%) at LT, but these
      rates were significantly higher than the rate for liver recipients with [(18)
      F]FDG-avid advanced HCC (21%, P = 0.002). In a multivariate analysis, negative
      PET findings (odds ratio = 21.6, P < 0.001), an alpha-fetoprotein level <400
      IU/mL (odds ratio = 3.3, P = 0.013), and a total tumor diameter <10 cm (odds
      ratio = 3.0, P = 0.022) were identified as pretransplant prognostic variables for
      recurrence-free survival. A PET(+) status was assessed as the only independent
      clinical predictor of tumor-related patient dropout from the waiting list (hazard
      ratio = 5.7, P = 0.01). Patients with non-[(18) F]FDG-avid HCC beyond the Milan
      criteria according to clinical staging may achieve excellent long-term recurrence
      free survival after LT.

PMID- 21850693
TI  - Hot-topic debate on hepatitis C virus: the type of immunosuppression matters.
AB  - KEY POINTS: 1. The treatment of rejection is an important factor associated with
      the severe recurrence of hepatitis C virus (HCV) after liver transplantation. 2.
      The effects of calcineurin inhibitors, corticosteroids, and mycophenolate mofetil
      on HCV recurrence are equivocal. 3. Cyclosporine is associated with a higher
      sustained virological response in patients treated for HCV. 4. Because insulin
      resistance and diabetes are associated with fibrosis in HCV-infected liver
      transplant recipients, the use of immunosuppressive agents without this side
      effect may slow the posttransplant disease progression.

PMID- 21850691
TI  - Carbon monoxide induces hypothermia tolerance in Kupffer cells and attenuates
      liver ischemia/reperfusion injury in rats.
AB  - Ischemia/reperfusion (I/R) injury in liver grafts, which is initiated by cold
      preservation and is augmented by reperfusion, is a major problem that complicates
      graft quality, posttransplant patient care, and outcomes of liver transplantation
      (LT). Kupffer cells (KCs) play important roles in I/R injury; however, little is
      known about their changes during cold preservation. We examined whether a
      pretreatment with carbon monoxide (CO), a cytoprotective product of heme
      degradation, could influence KC activity during cold storage and protect liver
      grafts against LT-induced I/R injury. In vitro, primary rat KCs were stimulated
      for 24 hours under hypothermic conditions (4 degrees C, 20% O(2)), with
      lipopolysaccharide, or under hypoxic conditions (37 degrees C, 5% O(2)) with or
      without a CO pretreatment. When rat KCs were exposed to hypothermic conditions,
      they produced reactive oxygen species (ROS), but they did not produce tumor
      necrosis factor alpha (TNF-alpha) or nitric oxide. The preincubation of KCs with
      CO up-regulated heat shock protein 70 (HSP70) and inhibited ROS generation. When
      liver grafts from donor rats exposed to CO (250 ppm) for 24 hours were
      transplanted after 18 hours of cold preservation in University of Wisconsin
      solution, HSP70 expression increased in these grafts versus control grafts, and
      serum aspartate aminotransferase and alanine aminotransferase levels as well as
      necrotic areas and inflammatory infiltrates were significantly reduced after LT.
      CO-pretreated liver grafts showed less up-regulation of TNF-alpha and inducible
      nitric oxide synthase messenger RNA (mRNA) and reduced expression of proapoptotic
      B cell lymphoma 2-associated X protein mRNA, cleaved caspase-3, and
      poly(adenosine diphosphate ribose) polymerase. In conclusion, the pretreatment of
      donors with CO ameliorates LT-associated I/R injury with increased hepatic HSP70
      expression, particularly in the KC population.

PMID- 21850694
TI  - The immunoreactive patient: Rejection and autoimmune disease.
AB  - KEY POINTS: 1. Despite highly potent immunosuppression regimens, there is a small
      cohort of patients at risk of graft failure due to rejection. 2. Steroid
      resistant rejection is managed by the escalation of immunosuppression, but only
      one-third of patients with chronic rejection respond to this approach. 3.
      Interferon therapy for recurrent hepatitis C may induce an immunoreactive state
      and increase rejection rates. 4. Cyclosporine reduces the risk of recurrence of
      primary biliary cirrhosis but does not alter survival rates. 5. Patterns of
      primary sclerosing cholangitis recurrence are not affected by immunosuppression.
      6. Autoimmune hepatitis recurrence and de novo autoimmune hepatitis are
      corticosteroid-responsive in most cases.

PMID- 21850695
TI  - Future prospects in immunosuppression for liver transplantation.
AB  - KEY POINTS: 1. Our increasing understanding of signaling pathways and cellular
      interactions in transplant immunobiology and the availability of novel
      immunosuppressive agents have facilitated targeted strategies. 2. The driving
      forces behind the development of new immunosuppressive regimens are the long-term
      complications of current immunosuppressive regimens (particularly renal
      dysfunction and metabolic disturbances). 3. By regulatory mandate, the
      requirement for the primary endpoint to be a composite of death, graft loss, and
      rejection remains intact; however, current and future clinical trials could
      incorporate key secondary endpoints that address renal and metabolic
      derangements.

PMID- 21850696
TI  - Hepatocellular carcinoma: agents and concepts for preventing recurrence after
      curative treatment.
AB  - KEY POINTS: 1. Adjuvant/neoadjuvant chemotherapy. 2. Neoadjuvant transarterial
      chemoembolization. 3. Kinase inhibitors (eg, sorafenib). 4. Antiviral treatment.
      5.Immunosuppressive treatment after liver transplantation. 6. Disseminated tumor
      cells: the basis for innovative treatment options?

PMID- 21850697
TI  - Present state of immunosuppressive therapy in liver transplant recipients.
AB  - KEY POINTS: 1. Our increasing understanding of the signaling pathways and
      cellular interactions in transplant immunobiology has facilitated targeted
      strategies using novel immunosuppressive agents. 2. The pattern of
      immunosuppressive drug use in the United States continues to change, and the
      changes include the use of antibody induction therapy and the agents used in
      maintenance therapy. 3. The driving forces behind the development of new
      immunosuppressive regimens are the long-term complications of current
      immunosuppressive regimens (particularly renal dysfunction and metabolic
      disturbances).

PMID- 21850698
TI  - Postoperative radiation therapy for small, low-/intermediate-grade parotid tumors
      with close and/or positive surgical margins.
AB  - BACKGROUND: Patients with small, low-/intermediate-risk parotid cancers, treated
      with surgery, and who have the single prognostic factor of close and/or positive
      margins, constitute an unusual subset. This study evaluates local control and
      morbidity associated with postoperative radiation therapy for low/intermediate
      grade parotid cancer in these patients. METHODS: Between 1999 and 2006, 17
      patients underwent postoperative radiation therapy at Beth Israel Medical Center
      for acinic cell carcinoma or low-intermediate-grade mucoepidermoid carcinoma of
      the parotid with close/positive margins. Pathology, treatment, and follow-up data
      were retrospectively analyzed for morbidity and local control. Two- and 5-year
      estimates of survival outcomes were performed followed by an analysis of
      complications. RESULTS: There were no local failures and no significant long-term
      complications. CONCLUSIONS: Patients with small, low-risk cancer of the parotid
      gland have excellent local control and low treatment-related morbidity when
      receiving postoperative radiation therapy for positive or close margins of
      resection.

PMID- 21850699
TI  - Relationship between serum thyroglobulin and 18FDG-PET/CT in 131I-negative
      differentiated thyroid carcinomas.
AB  - BACKGROUND: The purpose of this study was to assess the relationship between
      [(18) F]-fluorodeoxyglucose ((18) FDG)-positron emission tomography/CT ((18) FDG
      PET/CT) and serum thyroglobulin (Tg) in patients with recurrent differentiated
      thyroid carcinoma (DTC). METHODS: Forty-two patients with recurrent DTC and
      negative Tg antibodies were included in the study. All patients underwent (131) I
      therapy due to an increasing serum Tg with a corresponding negative (131) I
      posttreatment whole body scan. The (18) FDG-PET/CT scans were then performed on
      all patients, serum Tg was measured concurrently, and respective results were
      compared. RESULTS: Sensitivity, specificity, negative predictive value (NPV),
      positive predictive value (PPV), and accuracy of the (18) FDG-PET/CT examination
      were 93%, 84%, 93%, 84%, and 90%, respectively. The sensitivity of (18) FDG
      PET/CT significantly increased in patients with serum Tg levels >=4.6 ng/mL (96%)
      in comparison with patients having lower levels (25%; p < .001). Nonetheless, 3
      of 27 patients (11%) with a true-positive (18) FDG-PET/CT still had a Tg <4.6
      ng/mL. CONCLUSION: Although (18) FDG-PET/CT scans are more likely to be positive
      with pretest Tg levels >=4.6 ng/mL, 11% of patients with DTC with a lower serum
      Tg level will still have a positive scan. Our findings are in contrast with the
      American Thyroid Association (ATA) guidelines, which only recommend to perform
      (18) FDG-PET/CT in patients with Tg levels >10 ng/mL.

PMID- 21850700
TI  - Cancer stem cells in head and neck squamous cell carcinoma: a review of current
      knowledge and future applications.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and
      mortality, and the alleviation thereof requires greater understanding of the
      pathobiologic behavior of HNSCC. Although the existence of cancer stem cells
      (CSCs) in most solid tumors has not been formally proven, application of the CSC
      concept has certainly enhanced understanding of HNSCC heterogeneity and
      progression. Recent data support the role of ALDH1(+) CD44(+) CSC in HNSCC, since
      the implantation of a few ALDH1(+) CD44(+) cells consistently gives rise to
      tumors that can be serially passaged in vivo. In addition to CSC biomarkers,
      recent explorations of CSC signaling pathways, gene expression, and localization
      in HNSCC carry significant clinical and therapeutic implications. Identification
      and characterization of CSC populations that regulate HNSCC growth, metastasis,
      and treatment resistance will facilitate development of novel diagnostic,
      therapeutic, and prognostic strategies. Furthermore, advances in multimodal
      imaging and nanotechnology, in conjunction with CSC models, may better elucidate
      the regulatory mechanisms that govern CSC biology in vivo, as well as develop
      platforms for targeted theragnostics. It is hoped that the promising applications
      of the CSC model in HNSCC will eventually alleviate the morbidity and mortality
      of this pervasive disease.

PMID- 21850702
TI  - Odontogenic and nonodontogenic cysts in Istanbul: analysis of 5088 cases.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of 5088
      odontogenic and nonodontogenic cysts over a 40-year period in the Turkish
      population and to compare results with findings in the literature. METHODS: The
      records of odontogenic and nonodontogenic cysts, occurring during 1971 to 2010,
      were collected and analyzed for anatomic site, age range, and sex distribution.
      RESULTS: Among 5088 odontogenic and nonodontogenic cyst biopsies, 5003 cases
      (98.3%) were classified as odontogenic, whereas only 85 cases (1.7%) were
      nonodontogenic. In the former group, the most frequent diagnosis was radicular
      cyst (52.09%), followed by odontogenic keratocyst (20.6%) and dentigerous cyst
      (10.39%). Maxilla to mandible ratio was 1.13:1. The mean age of patients was
      36.33 years (range, 2-87 years). The cysts were slightly more prevalent among
      male patients (57.70%). CONCLUSIONS: The knowledge of the biological behavior and
      clinicopathologic features of jaw cysts constitute key aspects to provide early
      diagnosis and adequate surgery.

PMID- 21850701
TI  - Treatment-induced changes in vocal cord mobility and subsequent local recurrence
      after organ preservation therapy for laryngeal carcinoma.
AB  - BACKGROUND: As multidisciplinary cancer treatment evolves, strategies to identify
      patients needing early resection/salvage are necessary. Some have suggested that
      vocal cord function after organ-preservation treatment may be an indicator.
      METHODS: A retrospective review was performed of patients presenting with fixed
      or impaired vocal cord function at a tertiary center. Local recurrence rates were
      examined in patients with and without improved/normal mobilization after
      treatment. RESULTS: Sixty-nine patients met the inclusion criteria, with 35
      patients having vocal cord fixation and 34 patients with impaired mobility. After
      treatment, 44 patients had normalization of vocal cord function, while 25
      patients did not, with 2-year local control rates of 70% and 77%, p = .23,
      respectively. No difference in local control was found between patients with
      normalized/improved cord function (n = 53) and those who remained the
      same/worsened (n = 16; p = .81). CONCLUSION: Therapy-induced changes in vocal
      cord mobility did not correlate with local recurrence. Other criteria are needed
      to identify patients most likely to benefit from early surgical resection/salvage
      after organ preservation.

PMID- 21850703
TI  - Effects of different carboxylic ester spacers on chemical stability, release
      characteristics, and anticancer activity of mono-PEGylated curcumin conjugates.
AB  - We investigated the effects of different carboxylic ester spacers of mono
      PEGylated curcumin conjugates on chemical stability, release characteristics, and
      anticancer activity. Three novel conjugates were synthesized with succinic acid,
      glutaric acid, and methylcarboxylic acid as the respective spacers between
      curcumin and monomethoxy polyethylene glycol of molecular weight 2000 (mPEG(2000)
      ): mPEG(2000) -succinyl-curcumin (PSC), mPEG(2000) -glutaryl-curcumin (PGC), and
      mPEG(2000) -methylcarboxyl-curcumin (PMC), respectively. Hydrolysis of all
      conjugates in buffer and human plasma followed pseudo first-order kinetics. In
      phosphate buffer, the overall degradation rate constant and half-life values
      indicated an order of stability of PGC > PSC > PMC > curcumin. In human plasma,
      more than 90% of curcumin was released from the esters after incubation for 0.25,
      1.5, and 2 h, respectively. All conjugates exhibited cytotoxicity against four
      human cancer cell lines: Caco-2 (colon), KB (oral cavity), MCF7 (breast), and NCI
      H187 (lung) with half maximal inhibitory concentration (IC(50) ) values in the
      range of 1-6 uM, similar to that observed for curcumin itself. Our results
      suggest that mono-PEGylation of curcumin produces prodrugs that are stable in
      buffer at physiological pH, release curcumin readily in human plasma, and show
      anticancer activity.

PMID- 21850704
TI  - Influence of Mg2+, Ni2+, and Cu2+ on DNA assembly on HOPG surfaces: atomic force
      microscopy study.
AB  - Adsorption of circular DNA onto bare highly oriented pyrolytic graphite (HOPG)
      surfaces by the addition of Mg2+, Ni2+, and Cu2+ has been investigated by atomic
      force microscopy (AFM). AFM results revealed that the topography and height of
      DNA on HOPG surface by the addition of different metal ions are quite different.
      After the addition of Mg2+ for incubation, DNA molecules tend to form many loops
      on HOPG surfaces, which are derived from the crossover of intramolecular and
      intermolecular chains. After the addition of Ni2+, DNA molecules can form network
      on HOPG surfaces, and the density of DNA network was significantly increased with
      increasing DNA concentration. Consequently, dense DNA network can be obtained by
      using relatively low concentration of DNA and Ni2+. As for the addition of Cu2+,
      angular DNA loops composed of flat chains were observed. The observed flat DNA
      chains with an average height of 0.52 nm can be ascribed to Cu2+ insert into the
      site between bases and phosphate group of DNA inducing denaturation of DNA
      molecules. This study is very helpful for understanding the interactions of metal
      ions and DNA molecules, and for constructing various DNA structures on the
      carbonaceous surfaces.

PMID- 21850705
TI  - Ultraviolet radiation on innate immunity and growth of broad-snouted caiman
      (Caiman latirostris): implications for facilities design.
AB  - Sunlight is a key environmental factor in almost all ecosystems, and it is
      necessary for many physiological functions. Many vertebrates require ultraviolet
      (UV) radiation to perform different physiological processes. Artificial light is
      used to supplement UV in captive animals, through appropriate photoperiods and UV
      wavelengths. Previous studies reported that repeated exposure to artificial UV
      radiation may cause damage to the immune system. Taking into account the
      importance of UV effects and the serum complement system, the relationship
      between them was investigated. The study lasted 90 days and was carried out in
      plastic chambers. Ninety six broad-snouted caiman (C. latirostris) were assigned
      to four treatment groups with two replicates each: total darkness (TD), 8 hr per
      day (8 hr) and 16 hr per day (16 hr) of artificial UV/visible light exposure, and
      normal photoperiod of natural light (NP). Snout-vent length was measured to
      determine animal growth. Hemolytic assays were performed to evaluate the effects
      of artificial UV/visible light, TD, and NP on the serum complement system.
      Results showed that animals grew more in the NP group. The capacity of C.
      latirostris serum to hemolyze sheep red blood cells was higher in the NP group
      than when they are maintained in constant light-dark cycles (8 and 16 hr) or in
      TD. These data demonstrate that artificial UV should be considered as a potential
      hazard for captive crocodilians if it is not properly managed, and this should be
      taken into account in the general design of facilities for reptilian husbandry.

PMID- 21850706
TI  - Actin-depolymerizing factor homology domain: a conserved fold performing diverse
      roles in cytoskeletal dynamics.
AB  - Actin filaments form contractile and protrusive structures that play central
      roles in many processes such as cell migration, morphogenesis, endocytosis, and
      cytokinesis. During these processes, the dynamics of the actin filaments are
      precisely regulated by a large array of actin-binding proteins. The actin
      depolymerizing factor homology (ADF-H) domain is a structurally conserved protein
      motif, which promotes cytoskeletal dynamics by interacting with monomeric and/or
      filamentous actin, and with the Arp2/3 complex. Despite their structural
      homology, the five classes of ADF-H domain proteins display distinct biochemical
      activities and cellular roles, only parts of which are currently understood.
      ADF/cofilin promotes disassembly of aged actin filaments, whereas twinfilin
      inhibits actin filament assembly via sequestering actin monomers and interacting
      with filament barbed ends. GMF does not interact with actin, but instead binds
      Arp2/3 complex and promotes dissociation of Arp2/3-mediated filament branches.
      Abp1 and drebrin are multidomain proteins that interact with actin filaments and
      regulate the activities of other proteins during various actin-dependent
      processes. The exact function of coactosin is currently incompletely understood.
      In this review article, we discuss the biochemical functions, cellular roles, and
      regulation of the five groups of ADF-H domain proteins.

PMID- 21850707
TI  - Rab8 GTPase as a regulator of cell shape.
AB  - Endogenous Rab8 is found in dynamic cell structures like filopodia, lamellipodia,
      protrusions, ruffles, and primary cilia. Activation of Rab8 is linked to the
      formation of these actin containing structures, whereas inhibition of Rab8
      affects negatively their appearance. The activity of Rab8 is controlled by
      specific guanine nucleotide exchange factors and GTPase activating proteins. Rab8
      regulates a membrane recycling pathway that is linked to Arf6, EHD1, Myo5, and
      Rab11. A hypothesis is presented on the role of Rab8 in the formation of new cell
      surface domains. The review focuses on the function of Rab8 in cell migration,
      epithelial polarization, neuron differentiation, and ciliogenesis.

PMID- 21850708
TI  - Translational regulation mechanisms of aquaporin-4 supramolecular organization in
      astrocytes.
AB  - The two predominant isoforms of Aquaporin-4 (AQP4), AQP4-M23 and AQP4-M1,
      assemble in the plasma membrane to form supramolecular structures called
      Orthogonal Array of Particles (OAPs) whose dimension is tightly associated to the
      M1/M23 ratio. Here, we explore translational regulation contribution to M1/M23
      expression in primary cultures of rat astrocytes, and analyze the role of M1 mRNA
      5'untranslated region (5'UTR) in this mechanism. Using isoform-specific RNAi we
      found that in rat astrocytes primary cultures a large proportion of M23 protein
      derives from M1 mRNA translation. Furthermore, site-specific mutagenesis of the
      5'UTR sequence of AQP4-M1 mRNA indicates that a multiple-site leaky scanning
      mechanism, an out-of-frame upstream ORF (uORF), and a reinitiation mechanism are
      able to modulate the M1/M23 ratio and consequently, OAPs formation. These
      mechanisms are likely to be shared by different species, including human, and
      they can also be assumed to play a role in those pathophysiological situations
      where the organization of AQP4 in supramolecular structures (OAPs) is involved.
      Finally, we report that, when transfected in Hela cells, the longer rat AQP4
      isoform, called Mz, which is not present in human impairs OAPs formation.

PMID- 21850709
TI  - Eph receptors and ephrins in neuron-astrocyte communication at synapses.
AB  - Neuron-glia communication is essential for regulating the properties of synaptic
      connections in the brain. Astrocytes, in particular, play a critical and complex
      role in synapse development, maintenance, and plasticity. Likewise, neurons
      reciprocally influence astrocyte physiology. However, the molecular signaling
      events that enable astrocytes and neurons to effectively communicate with each
      other are only partially defined. Recent findings have revealed that Eph receptor
      tyrosine kinases and ephrins play an important role in contact-dependent neuron
      glia communication at synapses. Upon binding, these two families of cell surface
      associated proteins trigger bidirectional signaling events that regulate the
      structural and physiological properties of both neurons and astrocytes. This
      review will focus on the emerging role of Eph receptors and ephrins in neuron
      astrocyte interaction at synapses and discuss implications for synaptic
      plasticity, behavior, and disease.

PMID- 21850710
TI  - Mutation screening of the 3q29 microdeletion syndrome candidate genes DLG1 and
      PAK2 in schizophrenia.
AB  - Deletion of chromosome 3q29, which is associated with mental retardation and
      autism, was recently identified as being present in excess or occurring de novo
      in schizophrenia cases, being present in approximately 1/1,000 cases and 1/40,000
      unscreened controls. Of the ~20 genes in the commonly deleted region two are
      prominent candidates for involvement in the behavioral features of the
      microdeletion syndrome: DLG1 and PAK2. We report the result of mutation screening
      of the entire protein coding sequence of both genes in a sample of 234 unrelated
      cases and 272 unrelated controls from the UK. We find no evidence for any amino
      acid changing genetic variants in PAK2. We observe several rare and singleton non
      synonymous genetic variations at DLG1, however there is no excess of these
      variants in cases when compared to controls. Our sample was underpowered to
      detect very rare or low-penetrance disease relevant alleles in the studied genes.
      Therefore very rare, low-to-moderate penetrance protein coding mutations or non
      coding mutations at DLG1 and/or PAK2, or a nearby gene, may reproduce the
      behavioral characteristics of the 3q29 microdeletion.

PMID- 21850711
TI  - Sulfonic and phosphonic acid and bifunctional organic-inorganic hybrid membranes
      and their proton conduction properties.
AB  - Hybrid organic-inorganic approaches are used for the synthesis of bifunctional
      proton exchange membrane fuel cell (PEMFC) membranes owing to their ability to
      combine the properties of a functionalized inorganic network and an organic
      thermostable polymer. We report the synthesis of both sulfonic and phosphonic
      acid functionalized mesostructured silica networks into a poly(vinylidenefluoride
      co-hexafluoropropylene) (poly(VDF-co-HFP) copolymer. These membranes, containing
      different amounts of phosphonic acid and sulfonic acid groups, have been
      characterized using FTIR and NMR spectroscopy, SA-XRD, SAXS, and electrochemical
      techniques. The proton conductivity of the bifunctional hybrid membranes depends
      strongly on hydration, increasing by two orders of magnitude over the relative
      humidity (RH) range of 20 to 100%, up to a maximum of 0.031 S cm(-1) at 60 
      degrees C and 100% RH. This value is interesting as only half of the membrane
      conducts protons. This approach allows the synthesis of a porous SiO(2) network
      with two different functions, having -SO(3)H and -PO(3)H(2) embedded in a
      thermostable polymer matrix.

PMID- 21850712
TI  - Development of molecular imaging and nanomedicine in China.
AB  - The rapid progress of molecular imaging (MI) and the application of
      nanotechnology in medicine have the potential to advance the foundations of
      diagnosis, treatment, and prevention of diseases. Although MI and biomedical
      nanotechnology are still in a formative phase in China, much has been achieved
      over the last decade. This article provides a commentary on the development and
      current status of nanomedicine in China, with a selective focus on Chinese
      nanoparticle synthesis technology, the development of imaging equipment, and the
      preclinical application of novel MI probes.

PMID- 21850713
TI  - A new ratiometric fluorescent probe for detection of Fe(2+) with high sensitivity
      and its intracellular imaging applications.

PMID- 21850714
TI  - Deep-eutectic-solvent-assisted synthesis of hierarchical carbon electrodes
      exhibiting capacitance retention at high current densities.

PMID- 21850715
TI  - CO2 insertion into metal-carbon bonds: a computational study of Rh(I) pincer
      complexes.
AB  - Catalytic carboxylation reactions that use CO(2) as a C1 building block are still
      among the 'dream reactions' of molecular catalysis. To obtain a deeper insight
      into the factors that control the fundamental steps of potential catalytic
      cycles, we performed a detailed computational study of the insertion reaction of
      CO(2) into rhodium-alkyl bonds. The minima and transition-state geometries for 38
      pincer-type complexes were characterized and the according energies for the C-C
      bond-forming step were determined. The electronic properties of the Rh-alkyl bond
      were found to be more important for the magnitude of the activation barrier than
      the interaction between rhodium and CO(2). The charge of the alkyl-chain carbon
      atom, as well as agostic and orbital interactions with the rhodium, exhibit the
      most pronounced influence on the energy of the transition states for the CO(2)
      insertion reaction. By varying the backbone and the donor groups of the pincer
      ligand those properties can be tuned over a very broad range. Thus, it is
      possible to match the electronic and steric properties with the fundamental
      requirements of the CO(2) insertion into rhodium-alkyl bonds of the ligand
      framework.

PMID- 21850716
TI  - Total synthesis of 7-ethyl-10-hydroxycamptothecin (SN38) and its application to
      the development of C18-functionalized camptothecin derivatives.
AB  - A new chemical synthesis of SN38, the active metabolite of the camptothecin
      prodrug irinotecan, has been achieved in 12 steps from simple, commercially
      available starting materials. A mild and efficient FeCl(3)-catalyzed Friedlander
      condensation was successfully applied to construct the AB ring system.
      Functionalization of the C ring was accomplished by a vinylogous Mukaiyama
      reaction of an in situ generated N-acyliminium intermediate with a silyl enol
      ether. An intramolecular oxa Diels-Alder reaction efficiently constructed the D
      and E rings in one step. Successive asymmetric dihydroxylation and I(2) -based
      hemiacetal oxidation furnished the stereochemistry of SN38 with high
      enantiopurity. Utilizing the ABC-ring intermediate and a functionalized silyl
      enol ether permitted the synthesis of a number of new C18-functionalized SN38
      derivatives. Several of the novel SN38 derivatives that bore a C10 methoxy group
      were found to exhibit comparable or more potent inhibitory activity against the
      proliferation of cancer cells relative to SN38.

PMID- 21850717
TI  - Can a proton be encapsulated in tetraamido/diamino quaternized macrocycles in
      aqueous solution and electric field?
AB  - The proton-binding behavior of solvated tetraamido/diamino quaternized
      macrocyclic compounds with rigid phenyl and flexible phenyl bridges in the
      absence or presence of an external electric field is investigated by molecular
      dynamics simulation. The proton can be held through H-bonding interactions with
      the two carbonyl oxygen atoms in macrocycles containing rigid (phenyl) and
      flexible (propyl) bridges. The solute-solvent H-bonding interactions cause the
      macrocyclic backbones to twist to different extents, depending on the different
      bridges. The macrocycle with the rigid phenyl linkages folds into a cuplike shape
      due to pi-pi interaction, while the propyl analogue still maintains the
      ellipsoidal ringlike shape with just a slight distortion. The potential energy
      required for proton transfer is larger in the phenyl-containing macrocycle than
      in the compound with propyl units. When an external electric field with a
      strength of 2.5 V nm(-1) is exerted along the carbonyl oxygen atoms, a difference
      in proton encircling is exhibited for macrocycles with rigid and flexible
      bridges. In contrast to encapsulation of a proton in the propyl analogue, the
      intermolecular solute-solvent H-bonding and intramolecular pi-pi stacking between
      the two rigid phenyl spacers leads to loss of the proton from the highly
      distorted cuplike macrocycle with phenyl bridges. The competition between intra-
      and intermolecular interactions governs the behavior of proton encircling in
      macrocycles.

PMID- 21850719
TI  - A comprehensive panel of turn-on caspase biosensors for investigating caspase
      specificity and caspase activation pathways.
AB  - Caspases play a central role in apoptosis, differentiation, and proliferation,
      and represent important therapeutic targets for treating cancer and inflammatory
      disorders. Toward the goal of developing new tools to probe caspase substrate
      cleavage specificity as well as to systematically interrogate caspase activation
      pathways, we have constructed and investigated a comprehensive panel of caspase
      biosensors with a split-luciferase enabled bioluminescent read out. We first
      interrogated the panel of caspase biosensors for substrate cleavage specificity
      of caspase 1-10 in widely utilized in vitro translation systems, namely, rabbit
      reticulocyte lysate (RRL) and wheat germ extract (WGE). Commercial RRL was found
      to be unsuitable for investigating caspase specificity, owing to surprising
      levels of endogenous caspase activity, while specificity profiles of the caspase
      sensors in WGE agree very well with traditional peptide probes. The full panel of
      biosensors was utilized for studying caspase activation and inhibition in several
      mammalian cytosolic extracts, clearly demonstrating that they can be utilized to
      directly monitor activation or inhibition of procaspase 3/7. Furthermore, the
      complete panel of caspase biosensors also provided new insights into caspase
      activation pathways wherein we surprisingly discovered the activation of
      procaspase 3/7 by caspase 4/5.

PMID- 21850718
TI  - Crystal structures of novel allosteric peptide inhibitors of HIV integrase
      identify new interactions at the LEDGF binding site.
AB  - An optimised method of solution cyclisation gave us access to a series of
      peptides including SLKIDNLD (2). We investigated the crystallographic complexes
      of the HIV integrase (HIV-IN) catalytic core domain with 13 of the peptides and
      identified multiple interactions at the binding site, including hydrogen bonds
      with residues Thr125 and Gln95, that have not previously been described as being
      accessible within the binding site. We show that the peptides inhibit the
      interaction of lens epithelium-derived growth factor (LEDGF) with HIV-IN in a
      proximity AlphaScreen assay and in an assay for the LEDGF enhancement of HIV-IN
      strand transfer. The interactions identified represent a potential framework for
      the development of new HIV-IN inhibitors.

PMID- 21850721
TI  - Mixed conductivity, nonstoichiometric oxygen, and oxygen permeation properties in
      Co-Doped Sr3Ti2O(7-delta).
AB  - Electrical conductivity and oxygen permeation rates in Co-doped Sr(3)Ti(2)O(7
      delta) with Ruddesden-Popper type structures were investigated. The effects of
      metal dopants (M) in the Ti site of Sr(3)Ti(2)(M)O(7-delta) on the mixed
      conductivity were also studied. Doping of Sr(3)Ti(2)O(7-delta) with Co was found
      to be effective for improving the electrical conductivity as well as the oxygen
      permeation rate, which could be assigned to the increased oxygen vacancy
      concentration by doping Co(3+) into Ti(4+) sites. The nonstoichiometric oxygen of
      these oxides was measured by using a thermal gravimetric method. The creation of
      oxygen vacancies, which is compensated with Co(3+) doping, leads to higher oxide
      ion conductivity. The oxygen permeation rate monotonously increased with
      increasing amounts of Co in the Ti site. Sr(3)Ti(0.8)Co(1.2)O(7-delta) exhibited
      high oxide ion conductivity and a large oxygen permeation rate. The highest
      oxygen permeation rate achieved a value of 2.02 cc min(-1) cm(-2) at 1273 K for
      Sr(3)Ti(0.8)Co(1.2)O(7-delta). Neutron diffraction analysis and redox titration
      suggests that the oxygen diffusion occurs through oxygen vacancies in the
      perovskite block, but not through excess oxygen in the rock salt block.

PMID- 21850720
TI  - Water- and acid-mediated excited-state intramolecular proton transfer and
      decarboxylation reactions of ketoprofen in water-rich and acidic aqueous
      solutions.
AB  - We present an investigation of the decarboxylation reaction of ketoprofen (KP)
      induced by triplet excited-state intramolecular proton transfer in water-rich and
      acidic solutions. Nanosecond time-resolved resonance Raman spectroscopy results
      show that the decarboxylation reaction is facile in aqueous solutions with high
      water ratios (water/acetonitrile >=50%) or acidic solutions with moderate and
      strong acid concentration. These experimental results are consistent with results
      from density functional theory calculations in which 1) the activation energy
      barriers for the triplet-state intramolecular proton transfer and associated
      decarboxylation process become lower when more water molecules (from one up to
      four molecules) are involved in the reaction system and 2) perchloric acid,
      sulfuric acid, and hydrochloric acid can shuttle a proton from the carboxyl to
      carbonyl group through an initial intramolecular proton transfer of the triplet
      excited state, which facilitates the cleavage of the C-C bond, thus leading to
      the decarboxylation reaction of triplet state KP. During the decarboxylation
      process, the water molecules and acid molecules may act as bridges to mediate
      intramolecular proton transfer for the triplet state KP when KP is irradiated by
      ultraviolet light in water-rich or acidic aqueous solutions and subsequently it
      generates a triplet-protonated carbanion biradical species. The faster generation
      of triplet-protonated carbanion biradical in acidic solutions than in water-rich
      solutions with a high water ratio is also supported by the lower activation
      energy barrier calculated for the acid-mediated reactions versus those of water
      molecule-assisted reactions.

PMID- 21850722
TI  - Hexaazatriphenylene (HAT) versus tri-HAT: the bigger the better?
AB  - A new hexaazatriphenylene (HAT) derivative formed by the fusion of three HAT
      units has been prepared and its electronic and molecular structures have been
      fully characterized by optical and vibrational Raman spectroscopy,
      electrochemistry, solid-state UV and inverse photoemission spectroscopy (UPS and
      IPES), and by quantum-chemical calculations. A comparative HAT versus tri-HAT
      study was performed. The fusion of three HAT molecules causes modifications in
      the optical and electrochemical properties consistent with enhanced pi-electron
      delocalization attained in a bigger planar core. Such combined experimental and
      theoretical studies are useful to balance chemical design with supramolecular
      engineering directed to find enhanced characteristics for new organic
      semiconductor applications.

PMID- 21850723
TI  - Anion-templated supramolecular C3 assembly for efficient inclusion of charge
      dispersed anions into hydrogen-bonded networks.
AB  - The binding properties and conformational adaptability of a known nitrate/sulfate
      receptor N,N'-3-azapentane-1,5-bis[3-(1-aminoethylidene)-6-methyl-3H-pyran-2,4
      dione] (L) toward various charge-dispersed monoanions (HSO(3)(-), ClO(4)(-),
      IO(4)(-), PF(6)(-), and SbF(6)(-)) are considered. These anions template the
      folding of three HL(+) species through a self-assembly process into a new hollow
      supramolecular trication. During the self-assembly, all strong hydrogen-bond
      donors of the podand become coordinatively saturated by interactions with the oxo
      functionalities from other HL(+) molecules. In that way, only the weak hydrogen
      bond-donating groups in the exterior part of the receptor are accessible for
      anion binding. The investigated anions are accommodated in the hydrophobic
      pockets of the isomorphous hydrogen-bonded frameworks, which serve as a basis for
      selective crystallization from the highly competitive anion/solvent systems. This
      behavior is discussed in terms of size and geometry of the anions as well as the
      receptor's coordination capabilities to provide the most favorable surroundings
      for guest inclusion both in solution and in the solid state.

PMID- 21850724
TI  - Ruthenium(IV)-catalyzed isomerization of the C=C bond of o-allylic substrates: a
      theoretical and experimental study.
AB  - A general mechanism to rationalize Ru(IV) -catalyzed isomerization of the C=C
      bond in O-allylic substrates is proposed. Calculations supporting the proposed
      mechanism were performed at the MPWB1K/6-311+G(d,p)+SDD level of theory. All
      experimental observations in different solvents (water and THF) and under
      different pH conditions (neutral and basic) can be interpreted in terms of the
      new mechanism. Theoretical analysis of the transformation from precatalyst to
      catalyst led to structural identification of the active species in different
      media. The experimentally observed induction period is related to the magnitudes
      of the energy barriers computed for that process. The theoretical energy profile
      for the catalytic cycle requires application of relatively high temperatures, as
      is experimentally observed. Participation of a water molecule in the reaction
      coordinate is mechanistically essential when the reaction is carried out in
      aqueous medium. The new mechanistic proposal helped to develop a new experimental
      procedure for isomerization of allyl ethers to 1-propenyl ethers under neutral
      aqueous conditions. This process is an unique example of efficient and selective
      catalytic isomerization of allyl ethers in aqueous medium.

PMID- 21850725
TI  - Simultaneous detection of intracellular tumor mRNA with bi-color imaging based on
      a gold nanoparticle/molecular beacon.
AB  - The successful treatment of most cancers depends on early detection. Tumor mRNA
      as a specific marker provides new avenues to monitor tumor progression in the
      early stages and assesses response to treatment. However, single tumor mRNA
      testing usually yields "false positive" results because cancer is associated with
      multiple tumor mRNA. It is indispensable to develop simple and effective
      approaches for the detection of multiple tumor mRNA. In this study, we used a
      combination of tumor-specific mRNA markers to avoid the inherent limitations
      associated with the single-marker technique. A gold nanoparticle (AuNP) was
      assembled with a bi-molecular beacon (bi-MB), and termed AuNP/bi-MB, which
      simultaneously targeted to two types of tumor mRNA in breast cancer cells. This
      imaging agent could prevent effectively false positive results and provide
      comprehensive and dependable information for the early detection of cancer. It
      would be beneficial to identify the stage of tumor progression and assess
      treatment decisions with the real-time detection of the relative expression
      levels of tumor mRNA in cancer cells. This strategy would offer an appealing
      approach toward the early detection of cancer by using multianalysis of tumor
      mRNA.

PMID- 21850726
TI  - Visual scanometric detection of DNA through silver enhancement regulated by gold
      nanoparticle aggregation with a molecular beacon as the trigger.
AB  - A convenient and label-free scanometric approach for DNA assay was designed by
      integrating a metal-ion-mediated conformational molecular beacon (MB) and silver
      signal amplification regulated by gold-nanoparticle (AuNP) aggregation. The
      strategy was based on displacing the interaction between the target DNA sequence
      and a competitor Hg(2+) ion with a link DNA sequence. In the absence of the
      target DNA sequence, a link DNA sequence interacted with the Hg(2+) ions, thus
      forming an inactive cyclic conformation of the MB. This result led to the poor
      aggregation of polyadenosine-functionalized AuNPs (A-AuNP). In the presence of a
      target DNA sequence with a stronger affinity than that of the competitor,
      hybridization between the link DNA and target DNA sequences turned on the
      trigger. The polythymidine end of the resulting linear duplex structure could
      react with A-AuNP, thus leading to a cross-linking aggregation. This aggregation
      weakened AuNP-catalyzed silver enhancement on a spot substrate. Further, by using
      scanometric detection, the concentration of the target DNA sequence could be
      conveniently read out within a linear range from 1.0 to 30 nM. Interestingly, in
      the same amount of Hg(2+) ions, one-base mismatched DNA showed only 22% of the
      relative gray-scale intensity for the target DNA sequence at the same
      concentration, thus indicating good specificity. The designed approach, with the
      help of the ion-mediated conformational MB, was simple, cost effective,
      adaptable, and convenient and provided significant potential applications in
      clinical analysis.

PMID- 21850727
TI  - Highly efficient control of thrombin activity by multivalent nanoparticles.
AB  - We have demonstrated that the incorporation of sulfated galactose acid (sulf-Gal)
      into thrombin-binding-aptamer (TBA)-conjugated gold nanoparticles (TBA-AuNPs)
      enables highly effective inhibition of thrombin activity toward fibrinogen. AuNP
      bioconjugates (TBA(15)/TBA(29)/sulf-Gal-AuNPs) were prepared from 13 nm AuNPs, 15
      mer thrombin-binding aptamer (TBA(15)), 29-mer thrombin-binding aptamer
      (TBA(29)), and sulf-Gal. The numbers of TBA and sulf-Gal molecules per AuNP
      proved to have a strong impact on inhibitory potency. The best results were
      observed for 15-TBA(15)/TBA(29)/sulf-Gal-AuNPs (with 15 TBA(15) and 15 TBA(29)
      molecules per AuNP), which, because of their particularly flexible conformation
      and multivalency, exhibited ultrahigh binding affinity toward thrombin
      (K(d)=3.4*10(-12) M) and thus extremely high anticoagulant (inhibitory) potency.
      Compared to the case without inhibitors (the "normal" value), their measured
      thrombin clotting time (TCT) was 91 times longer, whereas for TBA(15) alone it
      was only 7.2 times longer. Their anticoagulant activity was suppressed by TBA
      complementary-sequence (cTBA)-modified AuNPs (cTBA(15)/cTBA(29)-AuNPs) at a rate
      that was 20 times faster than that of free cTBA(15)/cTBA(29). Thus, easily
      prepared, low-cost, multivalent AuNPs show great potential for biomedical control
      of blood clotting.

PMID- 21850729
TI  - NUAP (no unnecessary acronyms please).

PMID- 21850728
TI  - Acute ovarian failure underestimates age-specific reproductive impairment for
      young women undergoing chemotherapy for cancer.
AB  - BACKGROUND: The authors sought to describe the age-specific impact of infertility
      and early menopause after chemotherapy among reproductive age women with cancer.
      METHODS: A total of 1041 women diagnosed with cancer between the ages of 18 and
      40 years responded to a retrospective survey on reproductive health history. Five
      cancer types were included: leukemia, Hodgkin disease (HD), non-Hodgkin lymphoma
      (NHL), breast cancer, and gastrointestinal(GI) cancer. Survey questions addressed
      acute ovarian failure (cessation of menses after treatment), early menopause
      (menopause before 45 years old), and infertility (failed conception). Logistic
      regression was used to determine the proportions of acute ovarian failure and
      infertility based on age at diagnosis. Censored data methods were used to
      determine the probability of early menopause. RESULTS: Six hundred twenty women
      received chemotherapy alone. The percentage reporting acute ovarian failure was
      8%, 10%, 9%, and 5% for HD, NHL, breast cancer, and GI cancer, respectively.
      Acute ovarian failure increased significantly with age at diagnosis (P < .05). In
      subjects not reporting acute ovarian failure, the incidence of infertility was at
      least 40% at age 35 years and increased significantly with age at diagnosis in HD
      and breast cancer (P < .05). The estimated probability of early menopause was at
      least 25% at age 30 years and increased significantly with younger age at
      diagnosis in HD, NHL, and GI cancer (P < .05). CONCLUSIONS: For patients to
      receive appropriate counseling, it is important that they understand the
      potential increased risk of infertility and early menopause beyond that of acute
      ovarian failure. These findings can provide improved, age-specific counseling
      regarding reproductive impairment for young women diagnosed with cancer.

PMID- 21850730
TI  - Points of view: Avoiding color.

PMID- 21850731
TI  - A flow cytometry revolution.

PMID- 21850732
TI  - Guilt by phenotypic association.

PMID- 21850733
TI  - Profiling the sixth base.

PMID- 21850734
TI  - Single molecules made simple.

PMID- 21850735
TI  - The dynamic RNA world.

PMID- 21850736
TI  - Turning the lights on a few molecules at a time.

PMID- 21850737
TI  - Reply to M. Mohiuddin et al.

PMID- 21850738
TI  - [Glioblastoma multi-forms].

PMID- 21850739
TI  - An icon moves on: Floris Melbourne Garner, 1922-2011.

PMID- 21850740
TI  - Obituary. Stephen G. Holtzman.

PMID- 21850741
TI  - The role and value of ITPs to specialty training for general practice.

PMID- 21850743
TI  - New Joint Commissioning panel for mental health could help GPs to commission
      mental health services more effectively.

PMID- 21850742
TI  - When is a social care cut not a social care cut?

PMID- 21850744
TI  - Not safe as houses.

PMID- 21850745
TI  - This time, it's personal.

PMID- 21850747
TI  - Evolving language of mental health.

PMID- 21850746
TI  - Getting heard.

PMID- 21850748
TI  - Disability living allowance.

PMID- 21850749
TI  - A child in mind.

PMID- 21850750
TI  - Mental health services.

PMID- 21850751
TI  - ADHD in adults. Your guide to today's mental health issues.

PMID- 21850752
TI  - Doctor's orders.

PMID- 21850753
TI  - Network.

PMID- 21850754
TI  - Legal eye.

PMID- 21850755
TI  - Viewpoint: the role and independence of some mental health charities.

PMID- 21850756
TI  - HIV and mental health.

PMID- 21850757
TI  - Are you experienced?

PMID- 21850758
TI  - On the record: looking at ordinary people's tales of living with their mental
      illness. Interview by Alita Howe.

PMID- 21850759
TI  - Health service link up.

PMID- 21850760
TI  - [Elderly physicians' drug prescriptions. A case from my practice].

PMID- 21850761
TI  - Counterpoint: Should all stools be screened for Shiga toxin-producing Escherichia
      coli?

PMID- 21850762
TI  - Chemical contamination in Tohoku, with Lizzie Grossman and Winnie Bird.

PMID- 21850792
TI  - "We share a sacred secret": gender, domesticity, and containment in Transvestia's
      histories and letters from crossdressers and their wives.
AB  - After WWII in the United States, gender and sexual minorities began to construct
      social identities in a cold war climate hostile to gender and sexual
      transgression. The coming of the sexual revolution in the mid-1960s and 1970s
      unleashed forces that provided opportunities for these groups to demarcate their
      differences from one another, achieve visibility, and court public favor in a
      more permissive and tolerant society. In this article, I examine how a cohort of
      white, heterosexual crossdressers and their wives forged a redeeming social
      script in ways that seem counterintuitive to the "spirit of the times." The
      presence of transvestism within the sacred, idealized space of the American home
      produced tremendous anxiety on the part of these transvestite husbands and
      especially their wives. To deflect the stigma of sexual deviancy and sooth
      feelings of insecurity, these couples utilized strategies of containment and
      embraced the domestic ideal, even well into the sexualized and swinging
      seventies. Their strategic yet curious retreat into domesticity compels a second
      look at the consensus, conformity, and containment narratives that once dominated
      our scholarly imagination of intimate matters during the postwar years. Might
      current revisionist histories have gone too far in discrediting these potent
      forces? How do gender and sexual populations beholden to whiteness and notions of
      respectability fit within the sexual revolutions of postwar America?

PMID- 21850793
TI  - Between Egyptian "national purity" and "local flexibility": prostitution in al
      Mahalla al-Kubra in the first half of the 20th century.
AB  - This article traces prostitution in al-Mahalla in the first half of the 20th
      century as a regulated urban practice until the trade was outlawed in Egypt in
      1949. Studying prostitution during this period of exceptionally rapid growth and
      transformation not only provides a window on a particular type of illicit
      sexuality and public morality in a colonial context, it also gives us a hint as
      to gender relations and inter-communal relations on the invisible marginalized
      part of a provincial local community, and how it was socially transformed. I
      argue that the regulation of prostitution in Egypt in 1882 and 1905 created a
      sphere for a power contest between the colonial state and the local community,
      between nationalist discourse and the local way of life, and between public
      morality and private space. While nationalist discourse constructed one virtuous
      nation, the local community accepted the licensed prostitution quarter, and
      resisted secret prostitution. The people of the town actively and continually
      shifted boundaries on what was public and what was private, what was the state's
      responsibility and what was communal liability.

PMID- 21850794
TI  - Textiles as social texts: syphilis, material culture and gender in golden age
      Spain.
AB  - Whereas traditional social and health histories have viewed the garments of early
      modern patients accessing hospital care as evidence of their poverty, this
      article reinterprets the meaning of patient clothing in the context of a venereal
      disease hospital in Toledo, Spain, in the seventeenth century. Patients carefully
      selected what they wore as they entered the hospital to produce certain effects
      on local audiences. Thus, these choices can be understood as body scripts meant
      to be read in certain ways rather than mere reflections of actual social status.
      In a context of gendered and social pressures associated with women's sexuality,
      female syphilitic patients wore garments meant to emphasize respectability and
      thereby avoid a loss of reputation.

PMID- 21850795
TI  - Education, sex and leisure: ideology, discipline and the construction of race
      among South African servicemen during the Second World War.
AB  - During the Second World War (1939-1945), South African military authorities
      employed various regimes to mould white South African soldiers as citizens of a
      particular type. These coincided broadly with traditions of racial statehood
      identified by David Goldberg, and included attempts at ideological control -
      through the liberal Army Education Scheme, a compulsory adult education project -
      as well as disciplinary interventions, which concentrated on soldiers' sexuality.
      The ways that ordinary soldiers responded to these divergent discourses reminds
      us that whiteness in a racial state was elaborated not just from above, but also
      below. This observation raises some cautionary points for the writing of 'post
      social' history, and just as it demands that ordinary servicemen's actions,
      experiences and ideologies need to be related to the state and other modes of
      power, it reaffirms Geoff Eley's appeal for a 'new history of society'.Lines of
      investigation that explore attempts to educate, discipline and control white
      soldiers begin to challenge some of the conventional periodizations of SA
      history, particularly the notion that South Africa's 1940s represented an
      optimistic 'world of possibilities'.

PMID- 21850796
TI  - Emigrant psychoanalysts in the USA and the FBI archives.
AB  - Interest in the fate of the German psychoanalysts who had to flee Hitler's
      Germany and find refuge in a new nation, such as the United States, has
      increased. The "emigre research" shows that several themes recur: (1) the theme
      of "loss" of one's culture, homeland, language, and family; and (2) the
      ambivalent welcome these emigres received in their new country. We describe the
      political-social-cultural context that existed in the United States during the
      1930s, 1940s, and 1950s. Documentary evidence found in the FBI files of three
      emigre psychoanalysts, Clara Happel, Martin Grotjahn, and Otto Fenichel, are then
      presented in combination with other source material. This provides a provisional
      impression of how each of these three individuals experienced their emigration.
      As such, it gives us elements of a history. The FBI documents suggest that the
      American atmosphere of political insecurity and fear-based ethnocentric
      nationalism may have reinforced their old fears of National Socialism, and
      contributed to their inclination to inhibit or seal off parts of themselves and
      their personal histories in order to adapt to their new home and become
      Americanized. They abandoned the rich social, cultural, political tradition that
      was part of European psychoanalysis. Finally, we look at these elements of a
      history in order to ask a larger question about the appropriate balance between a
      liberal democratic government's right to protect itself from internal and
      external threats on the one hand, or crossover into the blatant invasion of civil
      rights and due process on the other.

PMID- 21850797
TI  - [High perinatal mortality].

PMID- 21850798
TI  - [Intraocular pressure in patients undergoing capsulotomy Nd: YAG laser].
AB  - OBJECTIVE: to demonstrate whether patients undergoing capsulotomy Nd: YAG laser
      developed intraocular hypertension after the procedure. METHODS: prospective, pre
      experimental before and after 2 measurements with post-test in patients with
      posterior capsular opacity from the Ophthalmology Service. Measurements of
      intraocular pressure (IP) before capsulotomy Nd: YAG laser, and three hours and
      one week later. RESULTS: we studied 47 patients, 29.8 % were men and 70.2 %
      women. We compared between visual acuity before and one week later (Wilcoxon test
      p = 0.00). IP after three hours and one week later, comparisons with Friedman
      test were done (p =0. 002). We compared the IP prior and one week later (Wilcoxon
      test, with p =0.815). IP before and three hours later were obtained (p = 0.001)
      and IP three hours and one week later ( p = 0.004). CONCLUSIONS: we found an
      increase in IP in the first hours after the capsulotomy Nd: YAG laser, which
      decrease gradually until reaching the values presented before the procedure, in
      not more than a week period. It is a quick and safe procedure to treat posterior
      capsular opacity.

PMID- 21850799
TI  - Bingham Dai, Adolf Storfer, and the tentative beginnings of psychoanalytic
      culture in China, 1935-1941.
AB  - This paper looks at the work of two figures who, while marginal to theoretical
      developments within the history of psychoanalysis, each briefly played an
      important role in the dissemination of analytical ideas in China, contributing to
      an early psychoanalytic culture there. Bingham Dai, a native of China, while
      studying for a PhD in sociology at Chicago, received instruction from Harry Stack
      Sullivan and a psychoanalytic training under Karen Horney's supervision. However,
      the neo-Freudian outlook with which this experience imbued him had its roots in
      an earlier encounter with his experiments in personality education first
      conducted on students in a Tientsin high school, and later in Shantung under the
      direction of the conservative Confucian scholar and reformer, Liang Shu Ming.
      These experiences convinced him that a less orthodox psychoanalytic perspective
      was what Chinese patients with psychological problems required. He returned in
      1935 to teach medical psychology to doctors at Peking Union Medical College,
      taking a few into analysis and treating some patients. However, the Sino-Japanese
      war brought these activities to a close and he left in 1939, just a few months
      after the former Freud publisher and Viennese emigre, Adolf Storfer, arrived.
      Storfer set about publishing "Gelbe Post," a German language periodical replete
      with articles on psychoanalysis, linguistics and Chinese culture. But limited
      finances, severe competition from a rival publisher, plus his own ill health,
      forced him to abandon this in spite of the support offered him through the many
      contributors in the international psychoanalytic community whose articles he
      published. The paper concludes by considering the relative historiographic fate
      of the men upon whom subsequent scholarship has been very unevenly focused.

PMID- 21850800
TI  - Swimming pools and asthma: a new risk or premature concern?

PMID- 21850801
TI  - Effleurage and petrissage: holistic practice in Thailand.

PMID- 21850802
TI  - Lenin, sexuality and psychoanalysis.
AB  - While Trotsky's relatively favourable adherence to Freudian ideas is well
      documented, little is known about Lenin's attitude toward psychoanalysis. The
      author's extensive research shows that, far from being the follower of Freudian
      ideas depicted by some historians, the father of the October Revolution rejected
      psychoanalytic theory and, in particular, the perspective he considered
      "idealistic" and the importance attributed to sexuality. Lenin's prudish
      personality, the influence of his wife Nadezhda Krupskaya and their ideology
      resulted in the exclusion of psychoanalysis from the construction of the New Man
      that Marxism was planning to undertake in Russia.

PMID- 21850803
TI  - Joan Riviere and the masquerade.
AB  - Although she published her paper "Womanliness as a masquerade" in 1929, Joan
      Riviere wrote it in 1928, the year that women in England got the vote. I want to
      consider the paper, her first original contribution to psychoanalytic thought, in
      the social and cultural context of the time, and then I shall focus on elements
      in it that relate to Joan Riviere's personal experiences and family influences
      that shaped her understanding of women and their sexuality. As well, I shall look
      at her views in relation to those of Freud, Klein and Jones. There is evidence
      that Riviere was speaking of herself in her descriptions of the "patient" in her
      paper, evidence that can be found in her diary and in the diary of her mother; as
      well as from interviews that I had with her daughter Diana. In addition there is
      a letter from Freud to Riviere that gives further evidence that she is writing
      about herself in this paper. The correspondence between Freud and Jones
      concerning Riviere and her analysis with Freud in 1922 also throws light on her
      experiences and on her personality that are similar to those of the "patient" she
      describes in "Womanliness as a masquerade."

PMID- 21850804
TI  - "Against all hushing up and stamping down": the Medico-Psychological Clinic of
      London and the novelist May Sinclair.
AB  - May Sinclair (1863-1946) was one of the first modern novelists to appropriate
      psychoanalytic theories in her works. She was an early reader of the new
      psychoanalytic techniques but, rather than embracing its theories wholeheartedly
      and unquestioningly, she synthesized those that appealed to her own psychology of
      womanhood. Moreover, Sinclair's position was a unique one. As well as a highly
      acclaimed novelist with a respected public voice, she was closely associated with
      the setting up of one of the first psychotherapeutic centres in Britain, the
      Medico-Psychological Clinic of London. In this paper, I argue that the eclectic
      psychoanalytic situations in which Sinclair places her literary heroines mirror
      the eclectic and potentially feminist endeavours of the medico-Psychological
      Clinic. I draw upon archival material, hitherto unexamined by literary critics
      and medical historians, to reflect upon the turbulent lifespan of the Clinic and
      the attempts to curtail its controversial practices.

PMID- 21850805
TI  - "Behind the poetic fiction": Freud, Schnitzler and feminine subjectivity.
AB  - In 1922 Sigmund Freud wrote to fellow Viennese author and dramatist Arthur
      Schnitzler: "I believe I have avoided you out of a sort of fear of my double."
      Through a series of reflections on this imagined doubling and its reception, this
      paper demonstrates that the ambivalent desire for his literary other attested by
      Freud's confession goes to the heart of both theoretical and historical questions
      regarding the nature of psychoanalysis. Bringing Schnitzler's resistance to Freud
      into conversation with attempts by psychoanalytically oriented literary scholars
      to affirm the "Doppengangertum" of the two men, it argues that not only
      psychoanalytic theories and modernist literature but also the tendency to
      identify the two must be treated as historical phenomena. Furthermore, the paper
      contends, Schnitzler's work stands in a more critical relationship to its
      Viennese milieu than Freud's: his examination of the vicissitudes of feminine
      desire in "Fraulein Else" underlines the importance of what lies outside the
      oedipal narrative through which the case study of "Dora" comes to be centered on
      the uncanny nexus of identification with and anxious flight from the other.

PMID- 21850806
TI  - Thinking about Winnicott and the origins of the self.
AB  - Reading Rodman's "Winnicott: Life and Work" has induced some considerations in
      the author who for years has shared Winnicott's "research analysis" in the field
      of potential space. Among these considerations is the rarely remarked affinity
      between Erikson and Winnicott in their view of human nature as well as in their
      seeing basic trust as the essence of good growth. For Winnicott particularly
      maternal functions have great maturational value, facilitating the process which
      takes infants from their first sensory experiences to mentalization, where father
      will exist in reality. The significance of illusion at different maturational
      stages is briefly considered as opposed to reality. To the latter a distant
      origin (possibly in foetal movements, which in utero meet resistance) has been
      attributed by Winnicott as mentioned in one of his last letter. "Meeting
      resistance one feels real" was one of his sayings (Gaddini, 2003).

PMID- 21850808
TI  - Reform. Is patient safety still in the right hands?

PMID- 21850807
TI  - Judicial review. The high price of justice.

PMID- 21850809
TI  - Public health. Value for money or small change?

PMID- 21850810
TI  - Exception to the rule. HCA's earnings show decline in surgeries.

PMID- 21850811
TI  - Priceless passion. $250,000 bill? Physician wants other docs included in setting
      costs of care.

PMID- 21850812
TI  - Disparity nation. Healthcare just one sector struggling to close gap between
      haves and have-nots.

PMID- 21850813
TI  - Troubles at home. Affordable Care Act's cuts for home health draw fire, with
      critics saying other changes could end up raising costs.

PMID- 21850814
TI  - Another cost of capital. Cash infusion can mean survival for a hospital, but also
      loss of independence.

PMID- 21850815
TI  - Largest biotechnology companies. Ranked by worldwide revenue in 2010.

PMID- 21850816
TI  - Head Start doesn't work. What do you do when a beloved program doesn't produce
      results?

PMID- 21850818
TI  - National Center for Tumor Diseases, Heidelberg, Germany.

PMID- 21850817
TI  - Baby mamas. Teen moms are reality TV's new stars. Is this a good thing?

PMID- 21850819
TI  - The Methodist Hospital Research Institute, Houston.

PMID- 21850820
TI  - Mills-Peninsula Medical Center, Burlingame, California.

PMID- 21850821
TI  - On working for GPs.

PMID- 21850822
TI  - Workforce. Make sure nurse numbers add up.

PMID- 21850823
TI  - Disinvestment. Cut with care.

PMID- 21850824
TI  - Technology. Uncharted territory.

PMID- 21850825
TI  - Vertical and diurnal characterization of volatile organic compounds in ambient
      air in urban areas.
AB  - More than half of the world's population lives in cities, and their populations
      are rapidly increasing. Information on vertical and diurnal characterizations of
      volatile organic compounds (VOCs) in urban areas with heavy ambient air pollution
      can help further understand the impact of ambient VOCs on the local urban
      environment. This study characterized vertical and diurnal variations in VOCs at
      2, 13, 32, 58, and 111 m during four daily time periods (7:00 to 9:00 a.m., 12:00
      to 2:00 p.m., 5:00 to 7:00 p.m., and 11:00 p.m. to 1:00 a.m.) at the upwind of a
      high-rise building in downtown, Kaohsiung City, Taiwan. The study used gas
      chromatography-mass spectrometry to analyze air samples collected by silica
      coated canisters. The vertical distributions of ambient VOC profiles showed that
      VOCs tended to decrease at greater heights. However, VOC levels were found to be
      higher at 13 m than at ground level at midnight from 11:00 p.m. to 1:00 a.m. and
      higher at 32 than 13 m between 7:00 and 9:00 a.m. These observations suggest that
      vertical dispersion and dilution of airborne pollutants could be jointly affected
      by local meteorological conditions and the proximity of pollution sources. The
      maximum concentration of VOCs was recorded during the morning rush hours from
      7:00 to 9:00 a.m., followed by rush hours from 5:00 to 7:00 p.m., hours from
      12:00 to 2:00 p.m., and hours from 11:00 p.m. to 1:00 a.m., indicating that the
      most VOC compounds in urban air originate from traffic and transportation
      emissions. The benzene-toluene-ethyl benzene-xylene (BTEX) source analysis shows
      that BTEX at all heights were mostly associated with vehicle transportation
      activities on the ground.

PMID- 21850826
TI  - Polymeric cracking of waste polyethylene terephthalate to chemicals and energy.
AB  - Polyethylene terephthalate (PET) is a widely used thermoplastic. PET residues
      represent on average 7.6 wt% of the different polymer wastes in Europe. Pyrolysis
      of these wastes is attracting increasing interest, and PET is a potential
      candidate for this thermal process. The paper measures and discusses the kinetics
      of the pyrolysis reaction in terms of the reaction rate constants as determined
      by dynamic thermogravimetric analysis, with special emphasis on the required
      heating rate to obtain relevant results. The product yields and compositions are
      also determined. Gaseous products represent 16-18 wt%. The amounts of
      condensables and carbonaceous residue are a function of the operating mode, with
      slow pyrolysis producing up to 24 wt% of carbonaceous residue. Major condensable
      components are benzoic acid, monovinyl terephthalate, divinyl terephthalate,
      vinyl benzoate, and benzene. The present paper complements previous literature
      findings by (1) the study of the influence of the heating rate on the reaction
      kinetics in dynamic pyrolysis tests, (2) the isothermal investigation in a
      fluidized bed reactor to pyrolyze PET, and (3) the assessment of upgrading and
      recovery of the products. The paper concludes with a proposed reactor
      recommendation for PET pyrolysis, in either the bubbling or circulating fluidized
      bed operating mode.

PMID- 21850827
TI  - Quantification and analysis of airborne bacterial characteristics in a nursing
      care institution.
AB  - Indoor air quality has become a critical issue because people spend most of their
      time in the indoor environment. The factors that influence indoor air quality are
      very important to environmental sanitation and air quality improvement. This
      study focuses on monitoring air quality, colony counts, and bacteria species of
      the indoor air of a nursing care institution. The regular colony counts in two
      different wards range from 55 to 600 cfu m(-3) Regression analysis results
      indicate that the bacterial colony counts have close correlation with relative
      humidity or carbon dioxide (CO2) but not with carbon monoxide (CO) or ozone (O3).
      Real-time PCR was used to quantify the bacterial pathogens of nosocomial
      infection, including Acinetobacter baumannii, Citrobacter freundii, Escherichia
      coli, Klebsiella pneumoniae, and methicillin-sensitive Staphylococcus aureus. The
      most abundant bacteria species in the air of the nursing care institution is E.
      coli.

PMID- 21850829
TI  - Optical characteristics of southeast Asia's regional aerosols and their sources.
AB  - The dominant optical characteristics of Southeast Asia (SEA)'s regional aerosols
      were determined from the cluster analysis of the 26 AERONET aerosol inversion
      products, including aerosol light scattering/absorption indicators and aerosol
      size/shape parameters retrieved from 2003 to 2007. The data sets were acquired
      from four stations: Bac Giang in Vietnam and Mukdahan, Pimai, and Silpakorn
      University in Thailand. The cluster analysis showed agreement among the aerosol
      optical characteristics, land cover/uses, season as the surrogate of the
      prevailing winds, and observations from the literature. The results of this study
      showed that during the northeast prevailing winds from mid-September to December,
      the high aerosol exposure events were most frequently observed over the upwind
      station and less often over the downwind stations. This aerosol exhibited a
      single scattering albedo (SSA) of approximately 0.95 (440 nm), a relatively low
      refractive index, and a larger fine-mode size, suggesting it had the
      characteristics of urban/industrial aerosols reported in the literature. These
      aerosol sources were upwind from Bac Giang, probably in eastern China. From
      January to April, the aerosol exhibited a lower SSA of approximately 0.90, a
      higher refractive index, and a smaller fine-mode size, suggesting biomass burning
      smoke reported in the literature. The SEA urban aerosol exhibited a mean SSA of
      approximately 0.90 (440 nm) or lower, and the coarse-mode aerosol, possibly road
      dust or soil dust, played a role from October to January when seasonal winds are
      strongest. The results from a canonical discriminant function analysis suggest
      that the dominant SEA aerosol clusters tended to be separated by a canonical
      function positively correlated with SSA, the fine-mode asymmetry factor, and the
      overall fine-mode size and negatively correlated with the refractive index.

PMID- 21850828
TI  - The calcination process in a system for washing, calcinating, and converting
      treated municipal solid waste incinerator fly ash into raw material for the
      cement industry.
AB  - Calcination is the second step in a washing-calcination-conversion system in
      which treated municipal solid waste incinerator fly ash and bottom ash can be
      reused as raw material in the cement industry and can decompose or stabilize
      hazardous compounds, reduce residue amounts, and alter residue characteristics.
      In this research, only fly ash is discussed. Chloride reduction is important if
      treated fly ash is to be reused in cement; however, the relationship between
      washed fly ash properties and chloride reduction by calcination is not well
      understood. This study used washed residues of three types of fly ash-raw fly ash
      (RFA) from the boiler or economizer of an incineration system, fly ash collected
      in a bag filter injected with calcium hydroxide (Ca(OH)2) for acid removal
      (CaFA), and fly ash collected in a bag filter injected with sodium bicarbonate
      (NaHCO3) for acid removal (NaFA)-in calcination experiments with varying
      temperature (400-1100 degrees C) and atmosphere (100% nitrogen [N2] at 25 mL/min
      or 10% oxygen [O2] [90% N2] at fluxes of 25, 50, and 75 mL/min). From the
      perspective of chloride reduction, heating to 1000 degrees C with 1-hr heating
      time, 1-hr holding time, and an atmosphere of 10% O2/90% N2 was most suitable for
      calcination. Under these conditions, chloride levels were reduced by 91, 52, and
      96% in washed residues of RFA, CaFA, and NaFA, respectively. Among the washed
      residues, the weight of the washed residue of NaFA decreased the most.

PMID- 21850830
TI  - Quantitative assessment of variability and uncertainty of hazardous trace element
      (Cd, Cr, and Pb) contents in Chinese coals by using bootstrap simulation.
AB  - The quantitative measurements of uncertainties regarding the contents of
      hazardous trace elements (HTEs) serve as a basis for better assessment of the
      geochemistry and mineralogical characteristics of coals and their environmental
      impacts. In this paper, by using bootstrap simulation methodology, a quantitative
      procedure was demonstrated to characterize the variability and uncertainty of HTE
      (Cd, Cr, and Pb) contents in Chinese coals, which were specified by 27 different
      provinces and mining areas. Original data samples for Cd, Cr, and Pb contents in
      Chinese coals were compiled and summarized from the results reported in published
      literature. Sampling distributions for uncertainties in statistics such as the
      mean, median, and confidence interval were calculated. The national average
      contents were estimated at approximately 0.61 microg/g for Cd, 30.37 microg/g for
      Cr, and 23.04 microg/g for Pb. The ranges of uncertainties for bootstrap samples
      of national HTE contents were nearly symmetrical, and the ranges of the 95%
      confidence interval for the arithmetic mean were relatively small, with relative
      uncertainties of -16.39% to +21.31% for Cd, -10.11% to +11.72% for Cr, and -8.55%
      to +8.64% for Pb. This shows that the arithmetic mean contents f HHTEs in Chinese
      coals are higher in southern provinces than those in northern provinces,
      obviously differing because of different coal basins. The high values of HTE
      contents occur in provinces such as Sichuan, Chongqing, Yunnan, Hubei, and
      Guangxi. Provinces with low contents are located in northwestern China and
      include Xinjiang, Qinghai, Gansu, and Inner Mongolia; this can be mainly
      attributed to the medium moisture content, low ash, and low sulfur content in
      coals. Several provinces with high HTE contents such as Ningxia for Cd, Guangdong
      for Cr, and Shaanxi for Pb may be associated with the representativeness of the
      original data samples.

PMID- 21850831
TI  - Improvements to standard methodologies for the analytical determination of metals
      in stationary-source emissions samples.
AB  - Deficiencies with the current European reference method for the analysis using
      inductively couple plasma-mass spectrometry of metals in samples from stationary
      emissions sources are presented based on experimental data obtained from real
      samples. The effect of these deficiencies on the quality and accuracy of data is
      highlighted with biases of up to 40% being observed in real samples. Suggestions
      to improve the performance of the standard method are presented. In particular,
      the beneficial effect of using a drift correction procedure to account for the
      decrease in instrument sensitivity observed during an analytical measurement
      series is demonstrated. It is shown that this corrective procedure results in
      substantial improvements to the accuracy of data produced.

PMID- 21850832
TI  - Nitrogen conservation in simulated food waste aerobic composting process with
      different Mg and P salt mixtures.
AB  - To assess the effects of three types of Mg and P salt mixtures (potassium
      phosphate [K3PO4]/magnesium sulfate [MgSO4], potassium dihydrogen phosphate
      [K2HPO4]/MgSO4, KH2PO4/MgSO4) on the conservation of N and the biodegradation of
      organic materials in an aerobic food waste composting process, batch experiments
      were undertaken in four reactors (each with an effective volume of 30 L). The
      synthetic food waste was composted of potatoes, rice, carrots, leaves, meat,
      soybeans, and seed soil, and the ratio of C and N was 17:1. Runs R1-R3 were
      conducted with the addition of K3PO4/ MgSO4, K2HPO4/MgSO4, and KH2PO4/MgSO4
      mixtures, respectively; run R0 was a blank performed without the addition of Mg
      and P salts. After composting for 25 days, the degrees of degradation of the
      organic materials in runs R0-R3 were 53.87, 62.58, 59.14, and 49.13%,
      respectively. X-ray diffraction indicated that struvite crystals were formed in
      runs R1-R3 but not in run R0; the gaseous ammonia nitrogen (NH3-N) losses in runs
      R0-R3 were 21.2, 32.8, 12.6, and 3.5% of the initial total N, respectively. Of
      the tested Mg/P salt mixtures, the K2HPO4/ MgSO4 system provided the best
      combination of conservation of N and biodegradation of organic materials in this
      food waste composting process.

PMID- 21850833
TI  - Effects of organic fertilizers on soil physicochemistry and on the yield and
      botanical composition of forage over 3 years.
AB  - Organic wastes have been reported to reduce saturation of the exchange complex by
      Al in Al-rich acid soils. For 3 years, the main soil fertility properties were
      studied in plots sown with mixed pasture species. These plots were fertilized
      with cattle slurry, dairy sludge (DS), or granulated broiler litter (BL) in
      comparison with mineral fertilizer. Al saturation levels were low after the
      initial inorganic liming treatment (19.00-33.71%) but tended to rise under all
      treatments (21.09-61.37%) except BL (8.45-30.98%), which was also associated with
      the highest average soil pH and the highest average levels of exchangeable Ca2+,
      Mg2+, and K+. Treatment DS performed similarly to mineral fertilizer in most
      respects, but it led to greater available P levels. Under the dry conditions of
      the second and third years of the study, BL and DS treatments were associated
      with significantly greater forage yields than the other treatments. Under DS
      treatment, available P levels were too low to allow the maintenance of mixed
      pasture, clover being eliminated by the less P-dependent species.

PMID- 21850834
TI  - Determining seasonal greenhouse gas emissions from ground-level area sources in a
      dairy operation in central Texas.
AB  - Greenhouse gas (GHG) emissions from agricultural production operations are
      recognized as an important air quality issue. A new technique following the U.S.
      Environmental Protection Agency Method TO-14A was used to measure GHG emissions
      from ground-level area sources (GLAS) in a free-stall dairy operation in central
      Texas. The objective of this study was to quantify and report GHG emission rates
      (ERs) from the dairy during the summer and winter using this protocol. A weeklong
      sampling was performed during each season. A total of 75 and 66 chromatograms of
      air samples were acquired from six delineated GLAS (loafing pen, walkway, barn,
      silage pile, settling basin, and lagoon) of the same dairy during summer and
      winter, respectively. Three primary GHGs--methane (CH4), carbon dioxide (CO2),
      and nitrous oxide (N2O)--were identified from the dairy operation during the
      sampling periods. The estimated overall ERs for CH4, CO2, and N2O during the
      summer for this dairy were 274, 6005, and 7.96 g head(-1)day(-1), respectively.
      During the winter, the estimated overall CH4, CO2, and N2O ERs were 52, 7471, and
      3.59 g head(-1)day(-1), respectively. The overall CH4 and N2O ERs during the
      summer were approximately 5.3 and 2.2 times higher than those in the winter for
      the free-stall dairy. These seasonal variations were likely due to fluctuations
      in ambient temperature, dairy manure loading rates, and manure microbial activity
      of GLAS. The annualized ERs for CH4, CO2, and N2O for this dairy were estimated
      to be 181, 6612, and 6.13 g head(-1)day(-1), respectively. Total GHG emissions
      calculated for this dairy with 500 cows were 2250 t of carbon dioxide equivalent
      (CO2e) per year.

PMID- 21850835
TI  - Particulate composition characteristics under different ambient air quality
      conditions.
AB  - Particulate compositions including elemental carbon (EC), organic carbon (OC),
      water-soluble ionic species, and elemental compositions were investigated during
      the period from 2004 to 2006 in southern Taiwan. The correlation between the
      pollutant standard index (PSI) of ambient air quality and the various particle
      compositions was also addressed in this study. PSI revealed a correlation with
      fine (r = 0.74) and coarse (r = 0.80) particulate matter (PM). PSI manifested a
      significant correlation with the amount of analyzed ionic species (r
      approximately 0.80) in coarse and fine particles and a moderate correlation with
      carbon content (r = 0.63) in fine particles; however, it showed no correlation
      with elemental content. Although the ambient air quality ranged from good to
      moderate, the ionic species including chloride (Cl-), nitrate (NO3-), sulfate
      (SO4(2-)), sodium (Na+), ammonium (NH4+), magnesium (Mg2+), and calcium (Ca2+)
      increased significantly (1.5-3.7 times for Daliao and 1.8-6.9 times for Tzouying)
      in coarse PM. For fine particles, NO3-, SO4(2-), NH4+, and potassium (K+) also
      increased significantly (1.3-2.4 times for Daliao and 2.8-9.6 times for Tzouying)
      when the air quality went from good to moderate. For meteorological parameters,
      temperature evidenced a slightly negative correlation with PM concentration and
      PSI value, which implied a high PM concentration in the low-temperature
      condition. This reflects the high frequency of PM episodes in winter and spring
      in southern Taiwan. In addition, the mixing height increase from 980 to 1450 m
      corresponds to the air quality condition changing from unhealthy to good.

PMID- 21850836
TI  - An unmissable opportunity.

PMID- 21850837
TI  - Nurses call for standardisation of pressure ulcer recording process.

PMID- 21850838
TI  - Health service chiefs call for pay flexibility to reward top workers.

PMID- 21850839
TI  - Ministers given nine months to produce social care funding plan.

PMID- 21850841
TI  - 'The health service needs a wider, long-term strategic plan'.

PMID- 21850840
TI  - Social networking site guidance issued in response to concerns.

PMID- 21850842
TI  - 'I wanted the world to know'.
AB  - A brutal regime at a care home exposed by the BBC's Panorama programme prompted a
      storm of protest. Terry Bryan explains how and why he blew the whistle.

PMID- 21850843
TI  - Round the clock care.
AB  - An intensive home treatment team operating around the clock is improving care for
      people with mental health problems.

PMID- 21850844
TI  - Staying power.
AB  - A student reflects on how she cared for children with malaria, then contracted
      the disease herself.

PMID- 21850845
TI  - Testing boundaries.
AB  - The Christie hospital's clinical trials unit plays a major role in testing new
      cancer treatments. The clinical research nurses who work there are vital to its
      success.

PMID- 21850846
TI  - Enhanced recovery after surgery and implications for nurse education.
AB  - This article examines three key aspects of the enhanced recovery after surgery
      (ERAS) initiative: improving pre-operative care, reducing the physical stress of
      surgery and increasing comfort after surgery. It also discusses changes in the
      role of the nurse and some of the implications for nurse education.

PMID- 21850847
TI  - Diabetes and its effects on wound healing.
AB  - This article discusses the reasons why wounds in people with diabetes take longer
      to heal and are more susceptible to complications. The physiology of the wound
      healing process, and how this is affected by diabetes, is outlined. The article
      also explains why wounds in patients with diabetes are more prone to infection
      and discusses preventive measures.

PMID- 21850848
TI  - Safeguarding vulnerable adults: the role of the registered nurse.
AB  - This article discusses vulnerable patient groups who may be at risk of being
      abused by family members, carers or practitioners. Different types of abuse,
      including institutional abuse, and the associated signs and symptoms are
      described. The article highlights that registered nurses working with adults need
      to be aware of at-risk groups and understand how to implement measures to protect
      and safeguard vulnerable individuals at their place of work.

PMID- 21850849
TI  - Healthy ageing.

PMID- 21850851
TI  - The power of information.

PMID- 21850850
TI  - Off to a flying start.

PMID- 21850852
TI  - Safety in numbers.

PMID- 21850853
TI  - Be inspired by the innovators.

PMID- 21850854
TI  - UK-wide audit into falls and fractures finds wide variation in quality of
      services.

PMID- 21850855
TI  - Inspection reports say dignity and nutrition still lacking.

PMID- 21850856
TI  - Beleaguered Southern Cross sets out national care strategy for industry.

PMID- 21850857
TI  - Living life to the full.

PMID- 21850858
TI  - Morbidity.

PMID- 21850859
TI  - Older people in care homes: sexuality and intimate relationships.
AB  - The Royal College of Nursing has developed guidance to help nurses and care staff
      work effectively with issues of sexuality, intimate relationships and sex,
      particularly for older people living in care homes. This article looks at the
      barriers to ensuring the sexual rights and freedoms of care home residents are
      protected and suggest how the new guidance might help.

PMID- 21850861
TI  - Winning ways for front line care.
AB  - The RCN's Frontline First campaign is highlighting examples of nursing
      innovations that have improved care while saving money after its research found
      that thousands of posts are at risk as NHS organisations cut costs. In this
      article, Carol Davis talks to winner of the Frontline First award Marina Lupari
      about her work in developing a nurse-led scheme that has significantly reduced
      the amount of time older people with chronic conditions spend in hospital. The
      work of runner-up Carol Gill, who developed a pressure ulcer early warning
      system, is also profiled.

PMID- 21850860
TI  - Improving call bell response times.
AB  - AIM: To explore and compare call bell response times in two wards in a geriatric
      evaluation and management facility before and after the introduction of a suite
      of interventions aimed at decreasing patient falls. METHOD: Data on call bell
      response times were collected over two periods. The first were before
      implementation of falls prevention initiatives. Data were retrieved from the call
      bell system that detailed the time taken to respond to every call bell
      activation. A second period of data collection was conducted six months after
      implementation of the initiatives. RESULTS: Prioritising call bell response and
      raising staff awareness improved response to patient calls. There was a slight
      decrease in falls although call bell activations did not decrease. CONCLUSION:
      Strong leadership is necessary from nurse managers to stress the importance of
      prompt call bell response. Visual surveillance of high-risk fallers is important
      as they are generally unable to ring for assistance when required.

PMID- 21850863
TI  - One-woman show.

PMID- 21850862
TI  - Making better use of older people's narratives.
AB  - For some nurses, conversations with an older patient are simply the backdrop to
      caregiving; they represent social pleasantries that help to dignify the sometimes
      intimate work of the nurse. However, the narratives that patients share through
      conversations, the way in which incidents or feelings are expressed, can provide
      valuable additional information that can be used to improve care. This article
      explores what analysis of narratives has to offer the care of older people and a
      way of nursing that works more closely with patients' experience of illness,
      treatment and support. Narrative analysis is portrayed as one means to make
      nursing care more patient centred.

PMID- 21850864
TI  - [Homes for the dependent aged or the paradox management].

PMID- 21850865
TI  - [Geront'Expo Handicap Expo. Dependence and support to caregivers: two unavoidable
      priorities in 2011].

PMID- 21850867
TI  - [Psychomotor therapist at homes for the dependent aged. Interview by Brigitte
      Sifaoui].

PMID- 21850866
TI  - [Understanding malaise occurring in elderly people].
AB  - Due to the potential seriousness of its consequences, particular attention must
      be paid to malaise occurring in elderly people. It represents between 5 and 10%
      of hospital admissions of patients over the age of seventy. A full clinical
      examination as well as some additional examinations usually enable the cause(s)
      to be identified. Cardio-vascular and iatrogenic pathologies are the most
      frequent aetiologies.

PMID- 21850868
TI  - [For a true consensus in decision making].

PMID- 21850869
TI  - [Night rounds].

PMID- 21850870
TI  - [Framework and representation of night work in geriatrics].
AB  - Work organisations imposed on night nurses often do not take into account the
      specific nature of this particular space-time. In addition to the maltreatment of
      elderly people there is the malaise among nurses unable to find ways of changing
      this situation and who themselves are subject to constraints and suspicions.

PMID- 21850871
TI  - [Managing the night activity in a healthcare institute].
AB  - Over the long-term, night work can present risks for nurses' health and lead to
      an erosion of their skills. Managing these night shifts requires particular
      attention, going far beyond day-to-day management. Quality of care and working
      conditions are dependent on recruitment, training and mobility.

PMID- 21850872
TI  - [How do you sleep?].
AB  - A training course devoted to night work in geriatrics is an opportunity for
      nurses to question their relationship with sleep. Out-of-sync biological rhythms
      are not without consequence on nurses' health. However, nurses working night
      shifts appreciate the autonomy and solidarity within the team, as well as the
      special relationships which can be forged with the patients.

PMID- 21850874
TI  - [The night watchwoman's trolley].
AB  - In nursing homes, the presence of a nurse to watch over the residents at night is
      not required. The residents' sleep is thereby usually in the hands of a nursing
      assistant and a hospital housekeeper. It is thanks to their skills that they
      assure the continuity of care and the safety of the elderly people, without
      overstepping the boundaries of their roles.

PMID- 21850873
TI  - [Collaboration between the day shift and the night shift].
AB  - The care of elderly patients suffering from multiple pathologies requires a real
      continuity of care, and consequently, close cooperation between shifts. These
      principles must be applied by the different structures caring for elderly people
      as well as, and especially, within a single institution, between the day shifts
      and the night shifts.

PMID- 21850875
TI  - [Cognitive disorders in elderly patients at night].
AB  - The feelings of nursing staff towards working nights in nursing homes are little
      known, both with regard to the difficulties encountered in their activity as well
      as to the effects on their own life and health. Their practice is often
      complicated by the existence of behavioural disorders accentuated at night and
      which affect numerous residents.

PMID- 21850876
TI  - [Preserving the health of night nurses].
AB  - Sleep is a public health issue for nurses working night shifts. The risks
      incurred are not fully known and do not serve to limit the duration of the
      practice of working nights. A study carried out at Le Vinatier hospital, near
      Lyon in France, has resulted in management improving its approach to this issue.

PMID- 21850877
TI  - [Preventing rhythm desynchronization in shift work].

PMID- 21850878
TI  - [Sleep, an issue for nurses and patients].
AB  - A three-day training programme on sleep in hospitals was created in 2008 on the
      initiative of the national association for the continuing training of hospital
      staff, in collaboration with the French ministry of health. 448 nurses have been
      trained thanks to a participative programme integrating new, interactive
      pedagogical tools.

PMID- 21850879
TI  - [Bibliography elements].

PMID- 21850880
TI  - [Homes for the dependent aged].

PMID- 21850881
TI  - [Injuries of the female genitalia in cases of sexual assault].
AB  - Sexual violence is a global problem that particularly affects women and children.
      A retrospective analysis of 390 clinical-forensic examinations and 120 autopsies
      regarding injuries of the female genitalia in cases of sexual violence was
      performed. In the majority of cases no injuries of the female genitalia were
      found. Autopsy cases showed significantly more (and more serious) injuries of the
      genitalia than clinical forensic examinations (43 % vs. 25 %; p = 0.0004).
      Predominantly found were injuries of the external anogenital area, mostly tears
      or soft tissue lesions. In the current literature, data regarding the rate of
      injuries in victims of sexual violence vary strongly and their comparability is
      limited. Regarding the reconstruction of an offence, a forensic examination with
      an appropriate documentation of the injuries is evidently crucial.

PMID- 21850882
TI  - [Differentiation of epithelial cell types by cell diameter].
AB  - Genital swabs play an important role in cases of alleged sexual assault. The aim
      of our study was to see if epithelial cells from the vagina, glans penis, or
      mouth could be distinguished on the basis of size. Vaginal swabs were taken from
      12 women in different phases of their menstrual cycles; penile swabs were taken
      from 5 men, and mouth swabs were taken from 6 men and 6 women. For each swab, a
      sample was smeared across a microscope slide and allowed to dry. The dried
      epithelial samples were then viewed without any further processing with a
      "SteReoLumar.V12" stereo microscope. The microscope slide surfaces were divided
      into grids and all single epithelial cells whose contours could be clearly
      distinguished were photographed. The maximum diameter for each photographed cell
      was digitally determined using the Axiovision software. In total, 995 vaginal
      epithelial cells, 211 penile epithelial cells, 329 male oral epithelial cells,
      and 525 female oral epithelial cells were measured. Menstrual cycle phase did not
      affect vaginal epithelial cell diameter. The mean vaginal epithelial cell
      diameter was 63.95 microm (min. = 28.08 microm, max. = 108.06 microm, s = 11.50
      microm). The mean penile epithelial cell diameter was 39.24 microm (min. = 28.38
      microm, max. = 51.02 microm, s = 4.84 microm). The diameter of oral epithelial
      cells hardly differed for both sexes, although the female cells were, on the
      whole, slightly larger. On the basis of these results, it is not possible to
      conclude that epithelial cells of less than a certain diameter found in the
      assessment of a vaginal swab must be of penile origin. It is also not possible to
      usefully distinguish vaginal epithelial cells from male or female oral epithelial
      cells on the basis of the diameter. However, finding epithelial cells with a
      diameter distinctly greater than 50 microm in a penile swab sample suggests the
      presence of vaginal or oral epithelial cells. Epithelial cells examined with the
      presented method can be used without restrictions for further examinations, such
      as single-cell DNA analysis after single-cell picking with the micromanipulator
      developed by Aura Optik (Jena).

PMID- 21850883
TI  - [Clinical forensic examination findings and legal outcome in cases of suspected
      sexual child abuse].
AB  - The clinical forensic examinations conducted at the Institute of Legal Medicine
      of the Hanover Medical School between 1999 and 2008 in cases of suspected sexual
      abuse of children were evaluated retrospectively and analysed with regard to
      their legal outcome. In total, the study included 223 children (172 girls, 51
      boys) with a median age of 8.6 years. In 34 children (15.2%), forensically
      relevant diagnostic findings due to anogenital injury and/or detection of semen
      were recorded. Perpetrators were convicted more often when they were not a member
      of the victim's family. In cases with victims aged seven years or older,
      conviction was more common. The study shows that medical findings can best be
      preserved by an immediate clinical forensic examination. Suspected sexual child
      abuse can often not be proved by medical examination results, but in some cases
      diagnostic findings are not mandatory for conviction.

PMID- 21850884
TI  - [Diagnostic imaging in cases of suspected child abuse--focus craniocerebral
      trauma divergent guidelines and resulting problems].
AB  - For the clinical diagnosis of non-accidental craniocerebral trauma in children
      there are different recommendations and guidelines, which are not completely
      consistent. Depending on the examiner, the focus may be on therapeutic relevance,
      minimization of the exposure to radiation or potential conclusions as to the
      course of events. Under certain circumstances it may be difficult for the
      responsible institution to deal with all three perspectives, as is shown by the
      presented case. From the authors' point of view it would be desirable to work out
      a common guideline taking into account paediatric radiological and medicolegal
      aspects.

PMID- 21850885
TI  - [Variability of cannabinoid findings in blood].
AB  - Cannabis products have been administered for many centuries; today, cannabis is
      the most widely used illegal drug all over the world. Nevertheless, the
      interpretation of cannabis findings in blood with regard to consumption behaviour
      and/or estimating the elapsed time since the last cannabis use is still a very
      challenging task. A wide variation of pharmacokinetic parameters has been
      observed even in experimental studies. Different chemical structures of
      precursors, smoking dynamics, pyrolysis of phytocannabinoids and frequency of
      drug use affect the amount of THC absorbed. Polymorphic enzymes are involved in
      phase-I-metabolism of THC. Pharmacological effects of other cannabinoids or
      medication on the pharmacokinetics of THC have not yet been studied in detail.
      Hydrolysis of cannabis conjugates may occur during storage of blood samples and
      processing of specimens for analysis; knowledge on the stability of cannabinoids
      in forensic specimens is still poor. Whether determination of cannabinoid
      conjugates may be useful is a matter of further consideration. At present, the
      broad variation of pharmacokinetic parameters and the limiting factors discussed
      in the present paper should be taken into account when using data from
      experimental studies for interpretation of analytical results in forensic case
      work.

PMID- 21850886
TI  - Fending off the FTC. Defense that worked in Georgia may be increasingly used in
      antitrust cases.

PMID- 21850887
TI  - Don't celebrate yet. Between the courts and the Senate, there's much to fear on
      reform.

PMID- 21850888
TI  - Punishing the provider. Fear of tort system is driving some doctors away, thus
      limiting choices.

PMID- 21850889
TI  - Tapping young expertise. Time for a new generation in hospital boardrooms.

PMID- 21850890
TI  - Going home. Federal program aims to help nursing home patients move out of their
      institutional settings.

PMID- 21850891
TI  - 2011 IT Case Study Contest.

PMID- 21850892
TI  - Losing their distinctions. Attributes of deals by not-for-profits, investor-owned
      chains begin to blur.

PMID- 21850893
TI  - Model behavior. For docs looking to form an IPA, navigating antitrust issues can
      be tricky.

PMID- 21850894
TI  - Largest nursing schools. Ranked by graduates for 2009-10 school year.

PMID- 21850895
TI  - Hostile reception. Value-based purchasing changes get poor reviews.

PMID- 21850896
TI  - Joined at the hip. Purchasers recognize need to work with providers to reform
      payment systems.

PMID- 21850897
TI  - Preparing for the unknown. But exchange flexibility also encouraging: experts.

PMID- 21850898
TI  - First female MGMA CEO. Brings internal medicine, IT experience to job.

PMID- 21850899
TI  - Engine performance. Reimbursement cuts threaten local economies relying on
      hospital jobs.

PMID- 21850900
TI  - Par for doc pay? Annual compensation survey shows who gained the most and who
      lost ground.

PMID- 21850901
TI  - A change advocate and policy developer in practice.

PMID- 21850902
TI  - In recognition of family caregivers.

PMID- 21850903
TI  - Summer to do list: living up to trust.

PMID- 21850904
TI  - The heart of a true caregiver.

PMID- 21850905
TI  - HIPAA indictment. Doc charged with disclosing patient info.

PMID- 21850906
TI  - Split on taxes, entitlements. Debt deals, healthcare funding stir parties' ire.

PMID- 21850907
TI  - Standing firm on ACA. Despite flak, AMA won't withdraw its support.

PMID- 21850908
TI  - Still golden? More companies eyeing healthcare, but newcomers need to deliver
      real value.

PMID- 21850909
TI  - True value. Focus on accountable care to deliver what patients, payers want.

PMID- 21850910
TI  - Largest health insurers. Based on 2010 healthcare-related revenue from health,
      life and health statutory fillings.

PMID- 21850911
TI  - Tales of the unexpected--and the lessons therein for us all.

PMID- 21850912
TI  - Erythromycin for GI motility; sunscreens; enoxaparin in obesity.

PMID- 21850913
TI  - What caused these itchy white bumps on the wrists?

PMID- 21850914
TI  - A day in the life.

PMID- 21850915
TI  - Postexposure prophylaxis for HIV: pivotal intervention for those at risk.

PMID- 21850916
TI  - Recurrent pneumonia and fevers in a child with congenital heart disease.

PMID- 21850917
TI  - EDOU staffing by PAs: what are the effects on patient outcomes?
AB  - OBJECTIVE: An emergency department observation unit (EDOU) opened in April 2006
      staffed by physician assistants (PAs) and nurse practitioners (NPs). This study
      describes the complexity and outcomes of the EDOU patients to determine the
      effectiveness of staffing by PAs. METHODS: A retrospective chart review was
      performed of chest pain and trauma patients in the EDOU from April 2006 through
      May 2007. Patient characteristics, length of stay (LOS), and admission rates were
      recorded. Adverse events were monitored, and trauma patients were followed for 30
      days to evaluate for missed injuries. RESULTS: 531 chest pain patients and 364
      trauma patients were admitted to the EDOU during the study period. Average chest
      pain patient LOS was 14 hours and 32 minutes, and 12.2% of patients were admitted
      from the EDOU to an inpatient unit. For trauma patients, average LOS was 12 hours
      and 46 minutes, and 11.5% of patients were admitted to an inpatient unit. There
      were no deaths, intubations, or loss of vital signs. In 30-day follow-up, there
      were no significant missed injuries among trauma patients. CONCLUSION: PAs
      effectively cared for patients of moderate complexity in the two largest groups
      of utilizers of the EDOU.

PMID- 21850918
TI  - Laryngectomy: the silent unknowns and challenges of surgical treatment.

PMID- 21850919
TI  - Venous thromboembolism in cancer: what is the optimal treatment?

PMID- 21850920
TI  - Do drospirenone-containing oral contraceptives have a higher risk of VTE?

PMID- 21850922
TI  - Physician assistants for sale: will prescribe for food.

PMID- 21850921
TI  - Multiple sclerosis treatment: First oral drug, new antibody therapies.

PMID- 21850923
TI  - Pain and chronic diarrhea in an elderly cancer patient.

PMID- 21850924
TI  - Growth and development: in pediatrics, everything starts small.

PMID- 21850925
TI  - Case of the month. Autoimmune colitis secondary to CTLA-4 blockade.

PMID- 21850926
TI  - The immune system which adversely alter thyroid functions: a review on the
      concept of autoimmunity.
AB  - The immune system protect individual from many pathogens exists within our
      environment and in human body, by destroying them through molecular and cellular
      mechanism of B and T cells of immune system. Autoimmunity is an adverse relation
      of immune system against non- foreign substances leaving behind either alters the
      normal function or destroying the tissue involved. Autoimmunity occur in
      genetically predispose persons with familial connections. The autoimmunity to the
      thyroid gland mainly consists of Hashimato thyroiditis and Grave's disease, the
      two end of spectrum in thyroid function of hypo and hyperactivity, respectively.
      The thyroid stimulating hormone receptor, thyroglobuline, enzymes of thyroid
      hormones synthesis are targeted by autoantibodies and cell- mediated reactions.
      The aim of this review is to explore the studies reported on the autoimmunity to
      the thyroid gland.

PMID- 21850927
TI  - Molecular cloning, characterization and overexpression of a novel cyclin from
      Leishmania mexicana.
AB  - We are reporting here, the cloning and characterization of the first cyclin from
      Leishmania mexicana. We have identified a cyclin-like motif from the L. major
      genome sequencing project. A cyclin homologue was cloned and sequenced from L.
      mexicana genome and it showed 96.1% amino acid identity with the putative L.
      major cyclin. It has also sequence identity to mitotic cyclins from other
      organisms. Southern analysis showed that it is present as a single copy gene.
      CYCa has been over-expressed in E. coli as a histidine fusion and western blot
      has confirmed the immunoreactive property of the recombinant cyclin, which then
      used to reconstitute active recombinant L. mexicana CRK3. No phosphorylation of
      histone HI was detected by both wild type and mutated CRK3 on the activation
      assays suggesting that phosphorylation status and cyclin binding are important
      for reconstituting protein kinase activity. The results confirm that we have
      isolated a cyclin molecule from L. mexicana (LmCYCa) which may play an important
      role in the regulation of the parasite cell cycle.

PMID- 21850928
TI  - Effects of oral administration of antioxidant taurine on haematological
      parameters in Wistar rats.
AB  - The present study evaluates the effects of oral administration of taurine on
      haematological parameters in normal wistar rats. Tissue oxidative stress is
      implicated in pathogenesis of various clinical disorders and antioxidant taurine
      is emerging as prophylactic and therapeutic agent. However, studies on effects of
      taurine on normal physiology are not reported in literature. Normal saline (Group
      I) or 5% taurine in normal saline was administered in dose of 50 mg (Group II),
      250 mg (Group III) or 500 mg kg(-1) of b.wt. (Group IV) through intragastric
      intubation for 60 days. The blood cell counts, haemoglobin content, packed cell
      volume, blood indices, bleeding time and clotting time were estimated using
      routine laboratory haematological techniques. Neutrophil's phagocytic activity
      was determined by nitroblue tetrazolium reduction test; serum lysozyme activity
      was estimated colorimetrically by the degree to lyse bacterial cell suspension
      and serum taurine levels were estimated by HPLC fluorimetric technique. Platelet
      count showed a decrease in Group III and IV when compared with Group I and II
      (p<0.001). Mean corpuscular haemoglobin of Group III and IV are significantly
      lowered when compared to Group I (p<0.001). A statistically significant decrease
      was observed in the mean corpuscular haemoglobin concentration between Group 1
      and Group IV (p<0.001). The neutrophil percentage of Group II, Group III and
      Group IV showed a significant increase over Group I (p<0.001). The percentage of
      lymphocytes showed a significant decrease in Group II, III and Group IV when
      compared to Group I (p<0.001). Neutrophil's phagocytic activity is significantly
      lowered in Group III and IV when compared to Group I (p<0.001). The serum
      lysozyme activity of Group III and IV showed a significant increase over Group I
      (at p<0.001). From the present study it may be concluded that long term oral
      administration of taurine affects normal haematological functions.

PMID- 21850929
TI  - Morphological identification of foodborne pathogens colonizing rice grains in
      south Asia.
AB  - The aim of this study was to identify the foodborne pathogens mainly, Aspergillus
      sp. colonizing rice grains using cultural and microscopic methods. Four
      differential media (Czapek Dox Agar (CZA), Czapek Yeast Agar (CYA), Malt Extract
      Agar (MEA) and Czapek yeast 20% sucrose agar (CYA20S)) were used for
      differentiation of five Aspergillus sp., colonizing rice grains comparing with
      standard cultures. We studied macroscopic (colony color and diameter, conidia
      color, exudates, sclerotia and colony texture) and microscopic (conidiophore
      color, length and breadth, conidia size, shape and surface texture, vesicle
      diameter and phialides length and breadth) characteristics for identification of
      110 isolates of Aspergillus sp. isolated from 65 rice grain samples collected
      from various countries in South Asia (Cambodia, India, Indonesia, Malaysia and
      Thailand). According to morphological characters, all these isolates were
      belonging to Aspergillus flavus (45), A. fumigatus (8), A. ochraceus (7), A.
      niger (42) and A. tamarii (8). This is the first report on identification of
      large number of Aspergillus strains isolated from rice grains in South Asia.

PMID- 21850930
TI  - Mid-piece length of spermatozoa in different cattle breeds and its relationship
      to fertility.
AB  - Recently positive correlation has been found between oxygen consumption (ZO2) in
      bull spermatozoa and non-return rates and concluded that an increase in ZO2,
      characteristic of the freeze/thaw process, was possibly associated with
      mitochondrial membrane damage during this procedure: alternatively, sperm may be
      hyperactivated through the capacitation-like effects of freezing/thawing. We
      speculated that the morphology of spermatozoa may be associated with their rate
      of ZO2 and fertility: for example, sperm mid-piece length where mitochondria are
      located. Such a relationship has not been investigated before, particularly in
      context of commercial cattle breeding programmes and bull fertility
      characteristics. Sperm biometry was performed on ejaculates obtained from 34
      bulls representing six breeds: Holstein (yearlings and mature), Friesian, Belgian
      Blue, Aberdeen Angus, Charolais and Limousin. Five ejaculates were collected from
      every bull and from each sample a semen smear was fixed and stained with
      eosin/nigrosin: the mid-piece length of 40 sperm with normal morphology was
      measured in every sample. Data were analysed by breed, age and within each bull.
      Significant differences (p<0.01) between ejaculates in 9/34 bulls was found, as
      well as differences (p<0.001) between individual bulls within the same breed. The
      average mid-piece length for Aberdeen Angus was 13.35 microm, for Belgian Blues
      and Limousin around 13.8 microm and for Charolais 13.68 microm: for dairy breeds
      such as Holstein and Friesian it was about 13.4 microm. The mean value of mid
      piece length for breed was compared with their 49 day non-return rate; a negative
      correlation (r = -0.53) was found in black and white dairy breeds.

PMID- 21850931
TI  - Synthesis of magnetic Al/Au nanoparticles by co-reduction of Au3+ and Al3+ metal
      salts.
AB  - In current study, it reported the synthesis of water soluble; monos disperse
      Al/Au bimetallic nanoparticles with a middling length of 7 nm. Synthesis engages
      concurrent reduction of Al3+ and Au3+ in water to give way bimetallic
      nanoparticles. The elemental content of Al is 1.5%. Nanoparticles display
      ferromagnetic performance as deliberate by SQUID. These particles can be
      effortlessly conjugated to thiolated DNA, as confirmation by mobility shifts in
      agarose gel electrophoresis. Nanoparticles heat in solution to temperatures above
      40 degrees C, representative appropriateness for hyperthermia.

PMID- 21850932
TI  - A review on the phytoremediation of petroleum hydrocarbon.
AB  - Oil spillage as a result of petroleum industry activities and pipe-line
      vandalization by saboteurs is a frequent occurrence in oil-producing regions of
      the world. Conventional oil spill clean-up techniques involve physical and
      chemical processes that do more damage to the aquatic ecosystem than the oil
      spill itself. Consequently, the need arises to evolve or develop a more
      environment-friendly technique that will not only clean-up the environment but
      also restore the aquatic ecosystem to its status before the oil spill.
      Phytoremediation, which involves the use of plant to detoxify polluted site,
      appears to be promising in this regard. It is environment-friendly as well as
      cost-effective but may take more time than the conventional methods because it is
      a natural process.

PMID- 21850933
TI  - Lipid peroxidation alterations in type 2 diabetic patients.
AB  - It was studied that type 2 diabetes mellitus is connected with increased plasma
      lipid peroxidation (lipid peroxidation expressed as malondialdehyde). This review
      aimed to evaluate the state of lipid peroxidation among type 2 diabetic subjects.
      Present finding showed that lipid peroxidation increased in type 2 diabetes
      mellitus. Increased lipid peroxidation maybe is associated with some diseases
      such as cancer, cardiovascular diseases and diabetes mellitus. Lipid peroxidation
      has an important role in the pathogenesis and the complications of diabetes.
      Antioxidants have been found to prevent the progression and occurrence of
      diabetes. There are several mechanisms that may cause lipid peroxidation affront
      in diabetic subjects, although, their precise contributions are not completely
      clear. We proposed that production of free radicals can be reduced by preventing
      high blood glucose levels and by the control of instabilities in blood glucose
      levels. A contributor to these instabilities in blood glucose is glycaemic
      control by using of fast blood sugar test. Furthermore, the earlier assessment of
      the advancement of diabetes that firmly control of blood glucose can be obtained;
      the greater will be the decrease in diabetic complications. Patients with type 2
      diabetes may have very high physiological antioxidants requirements.

PMID- 21850934
TI  - Fatty acid methyl ester from Neurospora intermedia N-1 isolated from Indonesian
      red peanut cake (oncom merah).
AB  - The objective of this study was to identify the Fatty Acid Methyl Ester (FAME)
      from Neurospora intermedia N-1 that isolated from Indonesian red peanut cake
      (oncom). FAME profiles have been used as biochemical characters to study many
      different groups of organisms, such as bacteria and yeasts. FAME from N.
      intermedia N-1 was obtained by some stages of extraction the orange spores and
      fractination using a chromatotron. The pure compound (1) was characterized by 500
      mHz NMR (1H and 13C), FTIR and LC-MS. Summarized data's of 1H and 13C NMR spectra
      of compound 1 contained 19 Carbon, 34 Hydrogen and 2 Oxygen (C19H34O2). The
      position of the double bonds at carbon number 8 and 12 were indicated in the HMBC
      spectrum (2D-NMR). LC-MS spectrum indicates molecular weight of the compound 1 as
      294 which is visible by the presence of protonated molecular ion [M+H] at m/z
      295. Methyl esters of long chain fatty acids was presented by a 3 band pattern of
      IR spectrum with bands near 1249, 1199 and 1172 cm(-1). We suggested that the
      structure of the pure compound 1 is methyl octadeca-8,12-dienoate. The presence
      methyl octadeca-8,12-dienoate in N. intermedia is the first report.

PMID- 21850935
TI  - Correlation between catecholamine levels and outcome in patients with severe head
      trauma.
AB  - Some studies have shown that catecholamines and the changes in their levels
      during and after head trauma can be useful in predicting the outcome in head
      trauma patients. The goal of this study is to search for a probable relation
      between urine levels of catecholamines and prognosis in patients with severe head
      trauma. Fifty four patients with severe head trauma Glasgow Coma Scale (GCS < or
      = 8) on admission time were recruited in Imam Reza Hospital within one. These
      patients were included when having no major accompanying trauma in other organs.
      Twenty four hour urine was collected after admission and levels of metanephrine
      and nor-metanephrine were measured. The relation between urine levels of these
      metabolites with final outcome and also with GCS at admission, 24, 48 h and 1
      week after admission and discharge time and Glasgow Outcome Scale (GOS) were
      studied. Fifty two patients, 48 males and 4 females with a mean age of 32.3 +/-
      14.7 (3-72) years were included. The main underlying etiologies were motorcycle
      (46.2%) and car accidents (25%). Diffuse axonal injury, brain contusion and
      subdural hematoma were three main diagnoses (28.8, 17.3 and 15.4% of the cases,
      respectively). 19 (36.5%) of the patients expired within the study period. The
      mean level of metanephrine and normetanephrine in urine were 207.9 +/- 200.5 and
      330.2 +/- 218.4 microg in 24 h, respectively. There was no meaningful relation
      between urine levels of these metabolites and any of GCS and GOS. There was also
      no meaningful relation between these parameters and final prognosis in patients.

PMID- 21850936
TI  - Prevention of selenite-induced cataractogenesis by Origanum vulgare extract.
AB  - The present study sought to assess antioxidant effect of Origanum vulgare extract
      in preventing selenite-induced cataractogenesis. This study was performed on
      Young white rats received sodium selenite (30 nmol g(-1) birth weight)
      subcutaneously on day 13 post partum during two months in 2009. Cataract
      formation and intensity was detected and measured by slit-lamp. Origanum vulgare
      (Ov) extract (2 g kg(-1)) was given (1-2 times) intraperitoneal at different
      times with respect to the selenite administration lens opacification was analyzed
      in selenite, selenite-Ov, Ov and control groups on day 7 after selenite
      administration. Ov extract have revealed a significant protective effect against
      selenite induced cataract when injected 1 and 2 day (2 times) before selenite
      injection. There is a protective effect of Ov against selenite induced cataract
      formation. It is supposed that the anticataract effect of Ov extract could be
      based on direct or indirect antioxidant mechanisms.

PMID- 21850937
TI  - The variation of the amount of the neurosecretory materials in the Corpus Allatum
      of Pimpla turionellae L. (Hymenoptera: ichneumonidae) during oocyte maturation.
AB  - The purpose of this study is to examine the effects of neurosecretory material
      (NSM) in Corpus Allatum (CA) of endoparasitic Pimpla turionellae L. on
      reproduction. For this purpose, the egg maturation of the insect and the amount
      of the NSM in CA of the serial section of the brain were studied. Egg maturation
      was determined by measuring the terminal oocyte length. In order to determine the
      amount of the NSM in CA the neurosecretory granules of which were stained by
      paraldehyde fuchsin are considered. The egg maturation of P. turionellae have
      performed twice. The NSM intensity in CA continued increasingly from the first
      day of egg development until the first oviposition days; and reached the maximum
      level before the second egg maturation phase. These observations showed that the
      NSM in CA of this insect may be related to egg development.

PMID- 21850938
TI  - Prevalence and underlying etiologies of neonatal hypoglycemia.
AB  - This study aims at determining the prevalence of neonatal hypoglycemia and its
      underlying causes. In this prospective study 14168 newborns delivered in Tabriz
      Alzahra Hospital during 2 years were evaluated in regard to blood glucose level
      at first 24 h of life. Glucose oxidase method with 4-aminophenazone with a
      Greiner G-300 was the used method for determining the blood glucose level. Cases
      with blood glucose < 50 mg dL(-1) were considered as hypoglycemic newborns.
      Underlying causes of this condition, as well as the short-term mortality rate
      were determined. Prevalence of neonatal hypoglycemia was 0.4% (52 newborns).
      Underlying causes of hypoglycemia were prematurity (61.5%), diabetic mother
      (13.6%), septicemia (9.6%), perinatal asphyxia (9.6%), stress (3.8%) and neonatal
      hyperinsulinism (1.9%). The mortality rate was 53.8%, with prematurity as the
      leading cause of death.

PMID- 21850939
TI  - Diagnostic accuracy of Doppler ultrasonography in differentiation between
      malignant and benign cervical lymphadenopathies in pediatric age group.
AB  - Cervical lymphadenopathy is a relatively common finding in pediatric age group
      and is caused by a wide spectrum of diseases from transient infections to
      malignancies especially lymphomas. The present study was aimed at evaluating the
      diagnostic performance of grey-scale ultrasonography, color Doppler
      ultrasonography and power Doppler ultrasonography in differentiation of
      reactively and metastatically enlarged cervical lymph nodes in pediatric age
      group. Fifty children with cervical lymphadenopathies were assessed by
      ultrasonographic methods. In each patient, the longest (L) and transverse (T)
      diameters, L/T ratio and presence or absence of the normal hilar pattern were
      checked by grey-scale ultrasonography. Spectral parameters (resistive and
      pulsatility indices) and vascular distribution pattern of nodes were recorded by
      color and power Doppler ultrasonography, respectively. Following the
      ultrasonographic evaluations, biopsy and/or clinical follow up was applied for
      six months, based on the clinical and paraclinical findings. Statistical analyses
      were performed by chi-square test, independent t-test and receiver operator
      characteristic curves. The mean age of patients was 12.42 +/- 2.42 years. Twenty
      eight patients (56%) had malignant enlargement of lymph nodes. The mean value of
      L/T ratio in malignant group was 1.70 +/- 0.22 and 2.40 +/- 0.38 in non-malignant
      nodes (p < 0.001). Sensitivity, specificity and accuracy of combined grey-scale
      and power Doppler ultrasonography were 70, 86 and 81%, respectively. Combination
      of grey-scale and power Doppler ultrasonography is recommended for the
      differentiation between the malignant and benign lymphadenopathies in children.
      Moreover, our findings revealed no diagnostic role of color Doppler
      ultrasonography in the selection of malignant cervical lymph nodes in children.

PMID- 21850940
TI  - Intra-arterial infusion of leptin does not affect blood pressure in salt-loaded
      rabbits.
AB  - The aim of this research is to see the effect of intra-arterial infusion of
      leptin on blood pressure of salt loaded rabbits in vivo. Increased blood pressure
      was produced in rabbits by giving diets containing 8% sodium chloride for 5
      weeks. Leptin in different concentrations was infused intra-arterially into
      rabbits fed on high salt diets and the response was compared in rabbits fed with
      low salt diets. High salt diets produced significant increase in blood pressure.
      In rabbits fed with low salt diet, leptin infused intra-arterially caused an
      increase in blood pressure while infusion of leptin into rabbits fed with high
      salt diets does not affect the blood pressure. In conclusion, salt loading to
      rabbits abolishes the effect ofleptin on cardiovascular system. This may indicate
      that leptin effect on sympathetic activity is altered by high salt diets in these
      animals.

PMID- 21850941
TI  - How we use the FMLA.

PMID- 21850942
TI  - Rugged's mass appeal.

PMID- 21850943
TI  - What is hazardous?

PMID- 21850944
TI  - The push for a'paradigm shift'.

PMID- 21850945
TI  - How the states see it.

PMID- 21850946
TI  - The future of the profession. Interview by Ronnie Rittenberry.

PMID- 21850947
TI  - Partners in prevention.

PMID- 21850948
TI  - The route to better data.

PMID- 21850949
TI  - Steel-toed assist.

PMID- 21850950
TI  - After the tornadoes. The safety training you do today has a very long lifespan.

PMID- 21850951
TI  - The most overlooked aspect of fall protection.

PMID- 21850952
TI  - Sleep apnea: causes and solutions.

PMID- 21850953
TI  - Time to upshift on driver wellness programs.

PMID- 21850954
TI  - Implementing HES&S training in the oil & gas industry: a brief overview.

PMID- 21850955
TI  - Fighting fatigue from the ground up.

PMID- 21850956
TI  - The value of precision notification.

PMID- 21850957
TI  - Persuading real leadership accountability.

PMID- 21850958
TI  - EM@IL and your patients. Too risky & time-consuming, or an idea whose time has
      come?

PMID- 21850959
TI  - Why majority control is so important. look before you leap when signing your next
      practice agreement.

PMID- 21850960
TI  - Are you ready for a HIPAA audit? Here's the information you'll need to be
      prepared in case investigators come calling.

PMID- 21850962
TI  - Giving, and getting, back to your practice and community. Service recognition
      model rewards doctors for extra work inside and outside of practice.

PMID- 21850961
TI  - A rocky road. Important lessons in life, love, and resilience from a special
      patient.

PMID- 21850963
TI  - Listening with the heart. Sometimes you have to really see patients to hear them.

PMID- 21850964
TI  - A time for renewal. A retired physician keeps things fresh by staying current in
      medicine and embracing new adventures.

PMID- 21850965
TI  - Key steps to make the grade. How to measure up with disease management.

PMID- 21850966
TI  - From the control of the world to the control of the control. Foreword.

PMID- 21850967
TI  - Nanotechnologies, bioethics and human dignity.
AB  - Nanoscale science, research, and technology present a complex set of
      circumstances. First of all, this field involves many different subjects,
      including biology, chemistry, physics, and environment sciences. Secondly,
      although scientists are working increasingly at a molecular level, nanotechnology
      is about much more than a reduction of scale. Indeed, nanoscience and
      Nanotechnologies offer an unprecedented ability to control and manipulate nature,
      offering hope for progress. Ethical perspectives vary considerably in this field,
      but commentators and researchers share a concern about a specific worrisome
      issue: the lack of appropriate ethical and legal principles and processes
      (associated with issues including health risks, human body manipulation, and
      private life violation), to guide nanotechnological R&D, commercialization, and
      final use. Some authors partially reject this concern by suggesting that
      Nanoscience and Nanotechnologies do not constitute an autonomous category, and
      that they are instead just the operative result of combining other traditional
      areas of study. However the nanotechnological debate brings up the semantic and
      content issues of bioethics and foments a contentious discussion emphasizing
      human dignity. Issues include enhancement versus therapeutic intervention,
      traceability versus privacy, and societal benefits versus risks. From these
      preliminary considerations, we will move on to discuss (I) the traditional,
      although still controversial, relationship between bioethics and human dignity,
      and (II) return to the subject of nanotechnology. We will discuss how today in
      Europe, although still indefinite, the principle of respect for human dignity is
      a welcomed contributor to "ethical vigilance" about the uncertain development of
      new nano-scale technologies. We will also note how U.S. strategy in this regard
      is simply lacking and appears only as a purely discursive "key issue in long term
      ".

PMID- 21850968
TI  - Cultural diversity in nanotechnology ethics.
AB  - Along with the rapid worldwide advance of nanotechnology, debates on associated
      ethical issues have spread from local to international levels. However unlike
      science and engineering issues, international perceptions of ethical issues are
      very diverse. This paper provides an analysis of how sociocultural factors such
      as language, cultural heritage, economics and politics can affect how people
      perceive ethical issues of nanotechnology. By attempting to clarify the
      significance of sociocultural issues in ethical considerations my aim is to
      support the ongoing international dialogue on nanotechnology. At the same time I
      pose the general question of ethical relativism in engineering ethics, that is to
      say whether or not different ethical views are irreconcilable on a fundamental
      level.

PMID- 21850969
TI  - The nanotech R&D situation in Japan and ethics of nanotechnology.
AB  - The aim of this paper is to introduce some characteristics of the historical as
      well as current situation of nanotech research and development in Japan in
      particular including regulations, and to discuss how ethical issues of
      nanotechnology should be addressed or how the ethics of nanotechnology should be
      constructed to fit the situation. The first part will center around the strength
      and weakness of Japan's nanotech R&D (research and development) and new
      circumstances which nanotechnology has prompted in Japan and alongside which
      nanotechnology has arrived (especially interdisciplinarity). The following
      prescriptive argument will, based on the descriptive account, question how to
      address ethical issues of nanotechnology, taking into consideration the nature of
      nanotech R&D, namely continuity, uniqueness, international dimension and
      political intervention, citing the example of the pharmaceutical industry. I will
      argue that international cooperation in the form of mutual reference to,
      replication of and the integration of guidelines and regulations, can enhance
      cost-effectiveness to ensure the comprehensiveness of regulatory measures.

PMID- 21850970
TI  - Cyborg identities and contemporary techno-utopias: adaptations and
      transformations of the body in the age of nanotechnology.
AB  - The possibility of improving the human body through a closer relationship with
      technology in order to overcome the human species toward new stages of evolution
      is a constant element of techno-utopian visions, among other transhumanism. This
      projection to a radical transformation of the body - and mind - as a result of
      technological action is based on the concepts of adaptation, or non adaptation,
      of a human being to a world constantly changed by technoscience. The belief is
      that not only the body has to change, but that identity is not a stable concept.
      This mobility in the relationship between body and identity is typical of the
      post human thought, which inherits from the informational model the conviction
      that the biological embodiment of human is to be regarded as an accident of
      history rather than as an essential condition of life. Hybridization is therefore
      valued by the post human thought as a condition which has "made" the human as he
      is today, and it appears as a fundamental topic in any discourse on
      nanotechnology, biotechnology and development of human-machine interfaces.

PMID- 21850971
TI  - Neuroscience and nanotechnologies in Japan--beyond the hope and hype of
      converging technologies.
AB  - Nanotechnologies are often said to be "converging" with other technologies like
      biotechnology, information technology, and cognitive science. And so-called "NBIC
      convergence" is thought to enable "enhancement" of human performance. First, I
      classify various kinds of enhancement. Second, I focus on the "cybernetic
      enhancement," to which nanotechnologies are supposed to contribute, and analyze
      the connection and integration of humans with machines, which could lead to the
      cyborgization of human beings. Third, I examine the portrayal of robot/cyborg
      technology in Japanese popular media, point out the tendency to empathy or
      ensoulment concerning robots/cyborgs, and raise the question of "ethical issues
      of ethical enhancement." Fourth, I compare nanotechnologies with neurotechnology
      and criticize the hype of "converging technologies."

PMID- 21850972
TI  - Legal aspects of the risks raised by nanotechnologies in the field of medicine.
AB  - The major breakthroughs achieved in nanotechnologies open new avenues in the
      field of healthcare--aid to diagnosis, upgrading medical treatment efficacy,
      development of regenerative medicine--but they are also associated with risks,
      hence the increasing need of legislation. So far very little research work has
      been conducted on this technology whose applications are still limited and whose
      potential hazards are not yet clearly apprehended. The more and more frequent
      uses of nanoparticles in medical imaging and in current research projects dealing
      with tissue engineering or RFID raises the following question: is the current
      legislative framework relevant in light of the specificities of nano-objects? The
      challenge is twofold: the legal approach must encompass the nanometric element
      itself as a "legal object" but it must include the use of nanotechnologies and
      their final aims. There is still some degree of uncertainty concerning the
      innocuity of nanoparticles so that the use of nanoelements in aid to medical
      diagnosis and in clinical trials must take into account and anticipate the
      potential harmful effects on patients and on biomedical research teams. But due
      to the fact that a clear understanding of nanoparticles as specific objects with
      new features is still missing, the existing regulations on chemical substances,
      medicinal products, medical devices or cosmetics do not seem to be appropriate.
      So considering nanoparticles as "singular" legal objects is a prerequisite
      requiring an approach based on the precautionary principle. Misusing
      nanotechnologies in the medical field is also a cause for great concern. Threats
      on individual freedom and on private life as well as on human identity are real
      and they raise recurring questions. The possible deviations in the use of these
      techniques, the temptations to "trespass the limits" are also common to info
      technologies and to biotechnologies but the threats triggered by the
      nanotechnologies are enhanced by the possibilities offered by the nanometric size
      and the expected convergence of these different technologies. One should refer to
      leading guiding principles in order to solve the future conflicts between the
      different sets of values, especially in the medical field by always remembering
      the Hippocratic oath "primum non nocere, deinde curare"

PMID- 21850973
TI  - Nanopatents and their impact on the medical environment.
AB  - The nano-medical field is seen, by governments as well as the business sector as
      a very promising one. The process of converting basic research in nanomedecine
      into commercially viable products has already begun, even if it might be long and
      difficult. Part of the difficulties that could occur comes from regulatory and
      safety issues. Some of them are also coming from patent uncertainty in the global
      nanotechnology field. Indeed, the rush towards patents in the nanotechnology
      arena has already begun. Nanopatents are about to alter the legal landscape of
      the innovation economy, of research and development, and of industry--no doubt to
      an unprecedented extent because of the scope covered by these technologies. From
      a global point of view, the very delineation of the scope of nanotechnologies
      confronts patent law with complex problems of definition. The emergence and
      characteristics of this technology are also giving rise to a reassessment of the
      criteria for patentability that could be prejudicial to innovation. In the
      medical environment, this issue is even exacerbated in the real challenges which
      pharmaceutical companies are running up against.

PMID- 21850974
TI  - Nanotechnology and environmental ethics.
AB  - It seems that the relation between human and nature is not direct, but mediated
      by the technology. Therefore, it seems that characteristics of the technology
      defines the relation. If this is true, the problem is whether new technology
      always makes new relation or not. In this paper I take a brief look at the
      relation between technology in general and the environmental crisis from the
      ethical perspective. And then, I investigate the concept of responsible
      development and the principle of stewardship that is adopted in two reports
      concerning nanotechnologies. Through these explorations, an ethical stance on the
      application of nanotechnology is proposed.

PMID- 21850975
TI  - [Testing doses? Environmental health stakes associated with nanotechnologies].
AB  - In this contribution, we analyse how nanoscience and nanotechnology have given
      birth to an important environmental health controversy regarding the potential
      sanitary dangers of engineered nanomaterials. We show how this controversy is
      part of a larger picture, made of a series of social and scientific disputes
      about the effects of man made chemicals on the human body. We show how these
      disputes have contributed throughout the 20th century to the emergence and the
      transformation of toxicology as a scientific field, and to test the robustness of
      the dose paradigm that constitues the cornerstone of this discipline. We suggest
      that the contemporary emergence of a new scientific field known as
      "nanotoxicolgy" must be interpreted as a successful adaptation of this paradigm
      to the specific toxicological questions raised by engineered nanomaterials.

PMID- 21850976
TI  - Nanomaterials and the environmental risk: is there some room left for ethics and
      law?
AB  - How legitimate may be the concern posed by the nanotechnologies for health and
      environment,this effort for reaching a better knowledge of the biotoxicity of
      nanomaterials is not enough. As Pr Didier Sicard noted, we believe that the
      ethical reflection should not be the good conscience that may help science in
      getting rid of social fears. But the ethical reflection is there also to discuss
      taboo issues in the perspective of a better societal understanding.

PMID- 21850977
TI  - [Employer's obligation of safety and nanomaterials].
AB  - Health and Safety law at work is influenced by the intervention of the European
      Union. The model of prevention of occupational risks is set by the 1989 framework
      directive. The question of its applicability to nanomaterials divides the
      Commission and the European Parliament. This model was welcomed differently by
      member states. Employers are generally under an obligation to adopt best means to
      assure workers' safety, while French law imposes an obligation to get results.
      This obligation concerns each aspect of the employment contract's execution and
      is analysed as an effective way to esure the prevention of occupational risks. If
      risks associated with nanomaterials seem to be taken into consideration by our
      system of worker protection, it seems however that prevention will be difficult
      to implement.

PMID- 21850978
TI  - [The foundation of research ethics in community law].
AB  - The creation of the European Community by the Treaty of Rome in 1957 marked the
      beginning of the efforts to coordinate and harmonize national policies in many
      strategic sectors with high economic value, among them several aspects of
      scientific research. The European Union Law, formerly known as European Community
      law, now includes a range of ethical principles that apply to research projects
      developed with the financial support of the European Union. Which were the steps
      in the integration of the ethics of sciences in the context of the Union? This
      article aims to study first, what were, and what are the legal bases of the
      integration of the ethical dimension of researches in life sciences by the
      European Union and, secondly, the institutional organisation that has been set up
      in order to discuss the development of common ethical norms, especially bioethics
      one, and in order to apply these rules which respect national particularities. In
      this regard, we analyse the relevant legal texts providing a foundation for the
      creation of a European bio-law and we give an overview of the European
      institutions' activity in the field of bioethics by looking particularly the
      health research field.

PMID- 21850980
TI  - Something for everyone. New practice models for primary care physicians offer
      revenue and lifestyle advantages.

PMID- 21850979
TI  - Cutting edge. A number of emerging practice models focus on lowering overhead,
      but how much is too much?

PMID- 21850981
TI  - Can you handle the truth? When it comes to identifying what makes an excellent
      practice manager, the truth is revealing.

PMID- 21850982
TI  - Avoiding lessee's remorse. Leasing office equipment offers many advantages over
      purchasing, but be sure to read the fine print.

PMID- 21850983
TI  - Create a strategy to protect your practice. A well-structured captive insurance
      plan allows you to stay competitive and reduce costs.

PMID- 21850984
TI  - Employee status carries some potential risks.

PMID- 21850985
TI  - Anaplastic large-cell lymphoma.
AB  - The concept of anaplastic large-cell lymphoma (ALCL) has changed over the years
      because of a stream of new information and novel understanding regarding the cell
      of origin, biology, genetics, and clinical features of these neoplasms. This new
      information has led to the current classification proposed by the expert
      reviewers of the World Health Organization. The objective of this review is to
      present the most updated information on the cytologic and histologic features of
      these entities, with a special reference to diagnostic algorithms. A detailed
      description of the genetic aberrations and the pathogenetic mechanisms leading to
      transformation is presented. The clinical features of ALCL and novel tailored
      strategies are briefly illustrated.

PMID- 21850987
TI  - Primary cutaneous lymphomas: a reprisal.
AB  - Primary cutaneous lymphomas (PCLs) are a group of lymphoid neoplasms provided
      with heterogeneous clinical, histological, immunohistochemical and molecular
      features. They can be classified in two groups: cutaneous T-cell lymphomas
      (CTCLs) and cutaneous B-cell lymphomas (CBCLs). Recent studies show an increase
      of the incidence of PCLs over the last three decades. Our aim is to evaluate the
      commonest types of PCL analysing the clinical characteristics, histology,
      phenotype, molecular biology, prognosis and therapy.

PMID- 21850986
TI  - Follicular helper T cells: implications in neoplastic hematopathology.
AB  - A distinct subset of T helper cells, named follicular T helper cells (T(FH), has
      been recently described. T(FH) cells are characterized by their homing capacities
      in the germinal centers of B-cell follicles where they interact with B cells,
      supporting B-cell survival and antibody responses. T(FH) cells can be identified
      by the expression of several markers including the chemokine CXCL13, the
      costimulatory molecules PD1 and inducible costimulator, and the transcription
      factor BCL6. They appear to be relevant markers for the diagnosis of
      angioimmunoblastic T-cell lymphoma (AITL) and have helped to recognize subsets of
      peripheral T-cell lymphoma, not otherwise specified, with nodal or cutaneous
      presentation expressing T(FH) antigens that might be related to AITL. In B-cell
      neoplasms, T(FH) cells are present within the microenvironment of nodular
      lymphocyte-predominant Hodgkin lymphoma and follicular lymphoma, where they
      likely support the growth of neoplastic germinal center-derived B cells.
      Interestingly, the amount of PD1+ cells in the neoplastic follicles might have a
      favorable impact on the outcome of follicular lymphoma patients. Altogether, the
      availability of antibodies directed to T(FH)-associated molecules has important
      diagnostic and prognostic implications in hematopathology. In addition, T(FH)
      cells could represent interesting targets in T(FH)-derived lymphomas such as
      AITL, or in some B-cell neoplasms where they act as part of the tumor
      microenvironment.

PMID- 21850988
TI  - Pathobiology of Epstein-Barr virus-driven peripheral T-cell lymphomas.
AB  - In the present review, the authors described the pathobiological features of
      Epstein-Barr virus (EBV)-driven T/natural killer cell-derived malignancies. These
      rare tumors appear to be quite heterogeneous with regard to both clinical and
      pathologic features. Nonetheless, some elements, especially regarding the
      possible role of EBV (ie, genomic predisposition, pathogenesis, pattern of
      latency), are similar, enforcing the concept of a causative role for the virus.
      In clinical practice, although definitely rare in Western countries, the tumors
      are not exceptional; thus, they should be taken into account in the differential
      diagnosis of T-lymphoproliferative disorders, also considering the need for
      extremely prompt intervention. The prognosis of such tumors is generally poor
      using current approaches. A better understanding of their molecular pathogenesis
      may lead to significant therapeutic improvements. For example, the nuclear factor
      KB pathway and platelet-derived growth factor receptor inhibition may represent 2
      options to be tested in clinical trials.

PMID- 21850989
TI  - Mantle cell lymphoma: recent insights into pathogenesis, clinical variability,
      and new diagnostic markers.
AB  - Mantle cell lymphoma (MCL; previously called centrocytic lymphoma or lymphocytic
      lymphoma of intermediate differentiation) is a distinct subtype of B-cell
      lymphoma, accounting for approximately 3%-10% of all lymphoma diagnoses. The name
      refers to the growth pattern in early disease presentation resembling the normal
      mantle zone that surrounds the germinal center of the B-cell follicle. The
      hallmark of MCL is the t(11;14)(q13;q32), resulting in aberrant expression of the
      CCND1 gene and expression of cyclin D1 in the tumor cells. Expression and genomic
      profiling of MCL have provided new insight into the pathogenesis and will be
      summarized in this review. Pitfalls in the differential diagnosis versus B-cell
      chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, cyclin D1-positive
      diffuse large B-cell lymphoma, hairy cell leukemia, and plasma cell tumors will
      be discussed, including the usefulness new diagnostic markers SOX11 and CD200. In
      situ MCL, MCL with an indolent clinical course, and cyclin D1-negative MCL are
      other topics of this review.

PMID- 21850990
TI  - [Physiotherapy in metaphysial hip replacement with use J&J Proxima stem].
AB  - In last years on the whole world violently grows up the number of patients at
      which occurrence productive degenerative changes of osteoarticular system.
      Actually these diseases more and more concern the young persons, active
      professionally. This consequences of these changes lead to limiting the
      functional functions of pond, pain as well as they worsen the quality of life.
      Pain in degenerative joint disease of various aetiology can be combated with the
      new surgical techniques offered by contemporary orthopaedics. Hip alloplasty is
      the only effective treatment method facilitating the restoration of physical
      fitness, correct mobility and the eradication of chronic pain. After operating
      introduces the different methods of improving finally. This work presents
      physiotherapeutic procedures, commenced on admission to the orthopaedic ward,
      involved in hip joint alloplasty with the J&J Proxima stem. The disseminating of
      introduced model of improving as well as the initiation him to program of the
      treatment confirms the legitimacy of choice, and it influences on improvement of
      the state of health also and the patients' functional efficiency with
      degenerative disease of hip joint.

PMID- 21850991
TI  - [The assessment of changes in radiological parameters of acetabulum of the hip
      joint according to position of the pelvis].
AB  - The aim of the study was to analyze the repeatability of selected radiological
      parameters in the assessment of mild forms of developmental dysplasia of the hip
      and to evaluate the changes of the parameters according the position of the
      pelvis. Retrospective review of radiographs of 98 hips (49 children) was done in
      antero-posterior and Lauenstein position. Among them 59 hips were treated for
      type II hip dysplasia according to Graf. At the latest follow-upthe mean age was
      9.1 years (range from 4 to 15 years). On radiographs in antero-posterior position
      of the hips mean rotation index (Tonnis-Brunken index) was 1.0, and on
      radiographs in Lange position was 0.98 and had no influence on measured
      parameters. On radiographs in antero-posterior position pelvis was more in
      forward rotation than in Lange position. With the pelvis in more forward rotation
      (measured using Ball-Kommend index) the value of Lequesne and Ullmanna-Sharp
      angles were decreased and Wiberg angle was increased. The angles had good
      repeatability. The other parameters: acetabular index, decentration distance and
      Idelberg-Frank angle were not statistically related to Ball-Kommend index.
      Idelberg-Frank angle had satisfactory repeatability but acetabular index and
      decentration distance had poor repeatability. Considering above mentioned
      characteristics of Idelberg-Frank angle, this parameter may be a useful tool for
      assessment of the hip.

PMID- 21850992
TI  - [Large diameter femoral heads in primary alumina/alumina and XSPE/alumina total
      hip arthroplasty. A follow-up study of 50 hips after average 40 months and review
      of literature].
AB  - INTRODUCTION: The aim of the study was a preliminary report of the use of large
      diameter alumina femoral heads in total hip arthroplasty. MATERIAL AND METHODS:
      In the years 2005-2008 50 THRs were implanted in 48 patients with the use of 36
      mm alumina femoral heads. 5 women and 43 men in the age from 35 to 75 years
      (average 61 years) were operated on. Primary osteoarthritis was the cause of 41
      arthroplasties, and AVN of femoral head of 9 surgeries. 18 alumina/alumina and 32
      polyethylene/alumina THRs were implanted. The prospective study consisted of
      clinical examination with Harris Hip Score and X-ray evaluation. AP and lateral
      view X-rays were evaluated. The incidence of radiolucent lines around acetabular
      cups were noted with DeLee and Charnley zones and around stems with Gruen's
      zones. RESULTS: The follow up is from 24 to 58 months (average 40 months). There
      was an increase in Harris Hip Score from average 37 points (from 25 to 49 points)
      before operation to average 94 points (from 90 to 100 points) after the surgery.
      The incidence of postoperative dislocation have not been noted. Long-term
      postoperative X-ray examination have showed proper geometry of endoprostheses
      without radiolucent lines. Neither visible wear of bearing surfaces nor breakage
      of alumina components have been noted. CONCLUSIONS: 1) The use of 36 mm femoral
      heads in total hip arthroplasty decrease the risk of postoperative dislocation.
      2) Innovative biomaterials: alumina ceramics and cross-linked polyethylene give
      chance for decrease the incidence of osteolysis.

PMID- 21850993
TI  - [Hip revision arthroplasty in massive bone loss of acetabulum with the use of
      reinforcement ring].
AB  - The aim of the study was the assessment of results after acetabular revision
      arthtoplasty with the use of reinforcement ring ReconShell (BBrown - Aesculap)
      and homogenous bone grafts. There were 49 patients in the study (42 women and 7
      men) in the age from 30 to 88 years. The follow-up period ranged from 4 to 48
      months. Before operation the mean Harris hip score was 31.14 and at last follow
      up 71.64 points. Aseptic loosening of reconstruction ring was found in 3
      patients. During next revision good integration of bone grafts, that were
      implanted into acetabulum at previous operation was found. In one hip revision of
      loose polietylen cup was performed. Three patient had early dislocation of hip
      endoprothesis, that were treated successfully in abduction casts. Next 2 patients
      had re-revision performed for recurrent dislocations. One patient had implants
      removal for septic loosening. Prolonged wound healing was noticed in 5 patients.
      Two patients had temporary and one permanent common peroneal nerve palsy. Two
      patients had temporary femoral nerve palsy. The use of reconstruction rings in
      massive bone loss of the acetabulum after cup loosening gives satisfactory
      clinical results. After the procedure patients have stabile joint that allows for
      weight bearing. Despite relatively high number of complications (most of which
      are temporary) this procedure is worth recommending.

PMID- 21850994
TI  - [Total hip replacement after slipped capital femoral epiphysis].
AB  - BACKGROUND: Total hip replacement (THR) is at present an accepted treatment in
      patients with severe osteoarthritis of the hip after slipped capital femoral
      epiphysis. The aim of this paper is to evaluate the results of THR in patients
      suffering from secondary osteoarthritis, operated from 1987 to 2004 in the
      Orthopaedic and Traumatologic Department of Poznan University of Medical
      Sciences. MATERIAL: Material included 16 patients, 9 females and 7 males, on whom
      18 THR were performed, lateral approach was used in all cases. At the time of
      operation, the age of patients ranged from 32 to 70 years (mean 50). THR was
      carried out after 33 years afterwards slippage of capital femoral epiphysis.
      Follow-up ranged from 6 to 23 years (mean 11 years). The operative treatment was
      a multistage process (during one operation only one joint was replaced). Cemented
      total hip arthroplasty was used during 5 of the THR, 13 of them were cementless.
      METHOD: The patients were clinically and radiologically evaluated preoperatively,
      postoperatively, and at final examination. The clinical state was evaluated with
      Harris hip score and WOMAC scale. We based our radiological examination on Hip
      Society system. RESULTS: The average preoperative Harris score for the group of
      patients was 32, WOMAC score 74. After an average of 11-years follow-up all hips
      were considered excellent, with average Harris score of 91, WOMAC Score of 6. All
      patients had increased function and decreased pain. The radiograms of all
      patients revealed that the acetabular and femoral components were correctly
      positioned with no radiographic evidence of loosening in the last examination.
      The inclination angle of the acetabular component was 22-49 degrees (mean: 36
      degrees) and the acetabular opening angle was 0-10 degrees (mean: 4 degrees). The
      stem was valgus-oriented in 1 hip, and neutral-oriented in 17 hips. No ectopic
      ossification concentrations were found. CONCLUSION: . Clinical and radiological
      evaluation of our material showed that total hip replacement in the treatment of
      osteoarthritis secondary to slipped capital femoral epiphysis allows regaining
      good lower limb function, which helps the patients staying less dependant on the
      surrounding environment. The results of THR are good regardless of the type of
      prosthesis and the type of fixation. Importantly, THR was carried out after a
      quite long time after slippage of capital femoral epiphysis.

PMID- 21850995
TI  - [Intervertebral disc calcification in children].
AB  - THE AIM: Evaluation of children with intervertebral disc calcification (IDC) and
      own experience. MATERIALS AND METHODS: A retrospective analysis of 7 patients (2
      girls and 5 boys) with detected, in the years 1990-2009, IDC. Age at the onset of
      symptoms (neck pain in 6 patients, torticollis in 4, hip pain in one) was on
      average 8.7 years (5-13 years). The diagnosis was based on review of radiographs
      of the spine, which revealed the presence of calcifications within the
      intervertebral discs in the cervical (4 patients), cervical and thoracic (2
      patients) and thoracic spine (1 patient). The mean level of IDC on average was
      3.3 spaces (1-6). RESULTS: After conservative treatment, including use of
      nonsteroidal anti-inflammatory drugs and rest, the symptoms subsided within 1-2
      weeks. 4 patients had a return of pain in the neck, in one year, but the symptoms
      were milder and resolved within a few days. The mean observation period was 9
      years (3.5-16 years). In 4 patients, changes disappeared completely, while in the
      remaining three there was a very discrete calcifications. One patient, after 6
      years, had a pain in the neck, and CT showed minor lytic changes on the surface
      of the vertebral bodies between which calcification occurred. DISCUSSION: s IDC
      is a rare disease of the spine in children, but should be taken into account in
      cases of vertebral pain. Usually the disease affects children before the age of
      10 and locates in the cervical spine. But it can be located in every segment of
      the spine. Most patients have multilevel location. Acute phase of the disease
      requires conservative treatment. Rarely used surgical treatment should be
      considered only in patients with persistant neurological symptoms. The natural
      course of the disease is mild, and over the years calcification gradually
      disappear spontaneously.

PMID- 21850996
TI  - [Osseointegration as a method of direct stabilization of amputation prostheses to
      the bone].
AB  - This article summarizes important advantages, disadvantages and the process of
      treatment of patients after lower limb amputation on the level of the femur, with
      osseointegrated prosthesis. In the process of treatment bone-integrated material
      is implanted to the femur, with allows for structural and functional connection
      between live tissue and the prosthesis. This solution allows the patient for easy
      usage and direct steerage of the prosthesis, transferring of body weight to the
      floor and detection of sensation in the moment of contact between prosthesis and
      the ground. Osseointegrated prostheses in the femur gives the opportunity not to
      use the traditional solutions and socket-related problems as: mobility
      difficulties, skin sores, rush, pain during weight bearing, temporary changes of
      the stump volume, difficulty donning the prosthesis, unreliability of prosthesis
      being securely suspended. Osseointegration is possible even in cases, when
      quality of skin and short stump enables to use the traditional prosthetic socket.
      It is used after lower and upper limbs amputations. This kind of prosthetic
      solutions has some disadvantages and limitations. It is expensive and demanding.
      It can be used in cooperative patients, who take active part in the process of
      implantation, rehabilitation and in future usage if the prosthesis.

PMID- 21850997
TI  - [Performance Matrix tests usage for diagnosing weak links of musculoskeletal
      system occurred in fencers].
AB  - AIM: The aim of this study is to find weak link or links of musculoskeletal
      system (locoutor system) occurred in fencers' body diagnosed by Performance
      Matrix Tests. ANALYSIS: The particular aim of this research is to estimate: if
      some weak links occur in a fencers' group, if all fencers in a group have the
      same weak links, if there is a correlation between weak links and training period
      length and if there is a connection between weak links and fencers' age.
      MATERIALS AND METHODS: Our research covered 14 f female and 14 male fencers from
      the Fencing Section at the Warta Club from Poznan. An average age of fencers was
      13.81 +/- 2.84.Performance Matrix Test was used there as a research tool, due to
      which the presence of musculoskeletal system's weak links was measured.
      CONCLUSION: The obtained results allow us to formulate the following conclusions:
      weak links of musculoskeletal system occur in a fencers' group, but it can not be
      given the exact answer if all fencers suffer from the same weak links. The
      research has not shown any evidences that there is a correlation between training
      period length and a number of weak links. Fencers' examination has not confirmed
      any correlations between fencers' age and the number of weak links. The tests
      have indicated that the most weak links appeared in a group of 12 years old
      fencers. Performance Matrix Tests are an easy and cheap tool for diagnosis of
      musculoskeletal system's weak link appearance. The early diagnosis of weak
      link/links can protect the fencer from musculoskeletal system's injuries. A lot
      of weak links found in fencers point out the need for undertaking work on local
      and global stabilization within a trunk and distal joints.

PMID- 21850998
TI  - [The analysis of patients with body traumas treated in the Military Medical
      Academy's Second Clinical Hospital of the Medical University of Lodz].
AB  - According to recent WHO reports, body traumas are ranked third with respect of
      frequency of occurrence right after cardiovascular diseases and tumours, and are
      considered one of the major medical problems. Trauma is a kind of energy
      (mechanical, thermal or chemical) affecting the human body. After crossing the
      threshold of tissue endurance, an injury or damage occurs. A common problem of
      all the centres that treat traumas is a reliable and comparable assessment of
      injury severity. Constant improvement of the trauma scores, contributes to
      increased objectivity of the assessment of injury severity and makes trauma
      research easier. To a large extent, commonness of the scores enables the exchange
      of experiences with respect to treating patients after trauma. An ideal scale
      should be reliable, easy to use, and most of all commonly used, thus enabling the
      employment of a common "traumatologic" language. In the following research, the
      test group was comprised of 137 adult patients including 113 men (82%) and 24
      women (18%). Most patients were aged from 20 to 60 years, that is, in the
      productive age. Appropriate trauma treatment results in the reduction of the
      costs of hospitalisation time of those patients and their recovery. An accident
      or worse still death of a young person is not only a personal tragedy for the
      family. It is also a big economic loss for the society which results from "lost
      years of life" and thus "lost years of work". Quick and appropriate treatment,
      done in a proper centre with appropriately trained staff and highest quality
      equipment will allow not only to reduce the victim's suffering and return to
      their daily life, but also minimise the social costs connected with disability
      pensions, benefits and compensations. Most injuries happened at work--61% were
      probably due to haste but most of all not complying with occupational health and
      safety regulations, which all employees should know and comply with. It involves
      doctors writing a sick note for the injured which undoubtedly involves much
      bigger losses for the employer and social costs in a form of increased premiums
      for healthcare plans. The most common mechanism of the injuries was self-injury
      (66.7%). In the study population, even 87% of the victims suffered from isolated
      body injuries. As is apparent from the analysed data, one should provide money
      for short-term health care, i.e. up to 2 days. The average treatment time for the
      study population was 4 days, with the maximum of 23 days. Most patients (60%)
      were brought by emergency medical services.

PMID- 21850999
TI  - [Assessment of life quality in children with spina bifida].
AB  - The aim of the study was identification and assessment of factors influencing
      quality of life in children with spina bifida. There were 33 children in the
      study (19 girls and 14 boys) in the age from 5 to 20 years. They were divided
      into 2 groups: first in the age from 5 to 12 years (17 patients) and second in
      the age from 13 to 20 years (16 patients). The Health-related Quality of Life in
      Spina Bifida Questionnaire and questionnaire done by us were used for the study.
      Younger children had average score of 158 points and older children average 186
      points. In the whole group 64% of children assessed they quality of life as good,
      30% as very good, 6% as average. None of our patients think that they quality of
      life is poor or very poor. Presence of visual perception difficulties in younger
      group and non-ambulation in alder children is related to poorer assessment of
      quality of life. Alder children that live in a house had better assessment of
      quality of life than children living in blocks of flats. Vast majority of
      children with spina bifida have good specialist medical care. Most common
      concomitant diseases are hydrocephalus and neurogenic urinary bladder.

PMID- 21851000
TI  - [Role of vascular endothelial growth factor and monocyte chemoattractant protein
      1 in the development of endothelial dysfunction in types 1 and 2 diabetes
      mellitus complicated by diabetic retinopathy].
AB  - The paper presents the results of a study of the serum levels of monocyte
      chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF)
      in 120 patients with types 1 and 2 diabetes mellitus complicated by diabetic
      retinopathy. All the patients with diabetes have been ascertained to show a rise
      in the levels of MCP-1 and VEGF. Calculation of VEGF/MCP-1 ratio is proposed to
      evaluate vascular bed lesion in diabetic patients.

PMID- 21851001
TI  - [Amino acid composition of amniotic fluid during physiological and complicated
      pregnancy].
AB  - An ion exchange chromatographic technique was used to study the content of 18
      free amino acids in the amniotic fluid of women with physiological and
      complicated pregnancy. The amino acid spectrum of amniotic fluid in placental
      insufficiency was found to be characterized by the lower content of arginine,
      serine, glycine, alanine, cysteine, tyrosine, phenylalanine, and glutamine, which
      are involved in many metabolic processes required to maintain biochemical
      homeostasis during gestation. There was an opposite tendency for dicarboxylic
      amino acids and histidine, the levels of which increased, by enhancing nitrogen
      imbalance. The degree of the found impairments of a number of amino acids
      considerably increased in case of birth of babies with brain lesions, which
      permits use of their amniotic fluid determination to predict the neonatal status.

PMID- 21851002
TI  - [Determination of capillary plasma C-reactive protein during therapy for acute
      infectious lung diseases].
AB  - Changes in the concentration of C-reactive protein (CRP), leukocytes, erythrocyte
      sedimentation rate, and differential blood count were comparatively estimated in
      the treatment of 66 infants (aged 1.12 +/- 0.95 years) with acute infectious lung
      diseases. There was a high correlation between capillary plasma and venous serum
      CRP concentrations. On the first day of effective antibiotic therapy, there was a
      significant decrease in CRP levels; the sensitivity and specificity were 96 and
      94%, respectively. Thus, measurement of capillary blood CRP is an accessible and
      informative tool to monitor therapy for infectious lung diseases in infants.

PMID- 21851003
TI  - [Alkaline phosphatase in mixed saliva in abdominal inflammatory diseases and
      gestoses].
AB  - By applying enzyme electrophoresis in the agar gel prepared on veronal-medinal
      buffer (pH 8.6) (the substrate was naphthol AS phosphate; the dye was fast blue B
      or PP), the authors first revealed mixed salivary alkaline phosphatase (AP) that
      differed in physicochemical properties from the known serum AP isoforms, in 63%
      of patients with cholecystitis or pancreatitis, in 90% of those with
      appendicitis, and in 55.3% of pregnant women with second- and third-degree
      gestoses. After treatment, the detection rate for salivary AP significantly
      decreased to 16.6, 40.0, and 6.4%, respectively. This noninvasive test may be
      useful for the additional diagnosis and monitoring of treatment for abdominal
      inflammatory diseases and gestational toxicosis.

PMID- 21851004
TI  - [Acute-phase proteins in the saliva of workers engaged in processing natural gas
      and condensate high in hydrogen sulfide].
AB  - The paper considers current methods for assessing the workers' health status. It
      shows it possible to identify increased quantities of acute-phase serum proteins
      upon exposure to the negative factors characteristic of the Astrakhan gas
      processing plant. A wider range of tests for acute-phase tissue and serum
      proteins is proposed to be included in order to gain a fuller insight into the
      influence of unfavorable industrial factors on man and to make monitoring that
      enables the existing health risks and the efficiency of preventive measures to be
      controlled.

PMID- 21851005
TI  - [The antioxidant system in patients with influenza and influenza pneumonia].
AB  - The paper deals with the topical theme--the state of antioxidant protective
      components in influenza infection. The values of catalase in red blood cells and
      those of ceruloplasmin in plasma were studied as an indicator of antiperoxide
      defense. The patients were grouped according to the severity of their condition
      and associated complications. The studies revealed a regular reduction in plasma
      ceruloplasmic levels at the height of influenza. In the waning period of clinical
      symptoms and in early convalescence, the parameter under study did not differ
      from that of healthy individuals. At the same time, the trend in influenza showed
      a significant increase in red blood cell catalase levels with the maximum values
      at the height of the disease and their normalization in early and late
      convalescence.

PMID- 21851006
TI  - [The serum levels of glycosaminoglycans and hydroxyproline in relation to the
      age, gender, and blood group of apparently healthy individuals].
AB  - The paper gives the results of a study of the levels of glycosaminoglycans (GAG)
      and hydroxyproline (HOP) in 87 apparently healthy individuals of both sexes, aged
      19 to 60 years. There is a decrease in the levels of GAG, total HOP, and peptide
      bound HOP with advanced age. These indices are higher in subjects less than 45
      years old than in those over the age. The found age differences are comparable
      with higher serum hyaluronidase and collagenolytic activities in subjects younger
      than 45 years than in those over the age 45 years. Collagen metabolism occurs
      more intensively in young subjects (under 45 years of age) than in old ones (over
      45). There are also gender-related differences: the men had higher levels of GAG
      and peptide-bound HOP and serum hyaluronidase activity than the women, which
      suggests that the metabolic rates of collagen and proteoglycans are higher. This
      difference is complimented by the qualitative characteristics of the process:
      there is a preponderance of the synthesis of collagen over its degradation with
      the accelerated degradation of proteoglycans in the young men. In Rh-positive
      subjects, the content of GAG was 22-fold higher than that in Rh-negative ones.

PMID- 21851007
TI  - [Reference values of clinical donor blood analysis].
AB  - Basic hemogram parameters were analyzed in 835 blood donors (421 men and 414
      women) aged 18 to 67 years) on an ADVIA 120 hematology analyzer. Reference ranges
      were calculated for each parameter in relation to their distribution (as X mean
      +/- 2alpha for normally distributed data and 2.5-97.5 per thousand for others).
      The findings suggest that the normal range should be extended for platelets, red
      blood cells, hemoglobin, and packed cell volume as compared with the earlier
      unified normal values, which must be taken into account when deciding whether a
      subject may be allowed to donate blood.

PMID- 21851008
TI  - [The specific features of the hemostatic system and platelet metabolism in
      pregnant women with gestosis for the prediction of the clinical status of
      neonatal infants].
AB  - The specific features of the hemostatic system and platelet metabolism were
      studied in women, who were 32-38 weeks pregnant and had varying gestosis, in
      relation to the clinical status of neonatal infants. The pregnant women who had
      higher levels of fibrinogen and soluble fibrin-monomer complexes along with
      decreased platelet enzyme activity regard their neonates' status as having Apgar
      scores of 6 or less and requiring additional medical intervention.

PMID- 21851009
TI  - [Determination of antibodies against cyclic citrullinated peptide in rheumatoid
      arthritis].
AB  - The ability of the synthetic peptide IMG-5, that reproduces one of the antigenic
      determinants of the protein filaggrin, to show antigenic activity was studied
      when anti-cyclic citrullinated peptide antibodies (ACCPAb) to filaggrin were
      found in the serum samples of patients with rheumatoid arthritis (RA). The
      binding of IMG-5 to ACCPAb has been shown to be specific (dose-dependent and
      reversible). The serum samples from patients with RA, controls, and donors show a
      significant difference in the interaction of the synthetic peptide with ACCPAb (p
      < 0.005 and p < 0.0001, respectively). The level of IgM rheumatoid factor (RF)
      detected in patients with RA differs greatly from that in the controls. In the
      patients with RA versus the controls, the specificity of ACCPAb determination was
      as high as 87; and the sensitivity was 40.5%. When ACCPAbs were determined using
      the commercial kit CCP, the specificity and sensitivity were 94 and 47.3%,
      respectively. The specificity of RF detection was equal to 50% and the
      sensitivity was 70%. The sensitivity of the test using IMG-5 is a maximum in X
      ray stage IRA (69.2%) and falls in its stage III (26.7%). On the contrary, the
      sensitivity of the commercial kit and RF determination increases from X-ray stage
      I (46.2 and 53.8%, respectively) to II (66.7 and 80%). The sensitivity of the
      used tests in varying RA activities has demonstrated that they are most effective
      in patients with moderate RA activity. The concurrent detection of ACCPAb and RF
      increases the probability of differentiating RA from other rheumatic diseases.

PMID- 21851010
TI  - [Current laboratory methods to evaluate the efficiency of immunization against
      dangerous and extremely dangerous infections].
AB  - By taking into account the leading role of specific cellular immunity in the
      development of protection against the majority of dangerous and extremely
      dangerous infections of bacterial, viral, and rickettsial nature, the study of
      the above immunity should be considered as most important on estimating the
      body's immunological rearrangement when vaccines against respective infections
      are administered. The battery of the test used to date for the analysis of
      specific cellular immunity is mainly restricted to skin tests that have
      disadvantages. This paper reviews the currently available laboratory methods for
      in vitro studies of a specific cellular immune response as a criterion for
      evaluating the efficiency of immunization.

PMID- 21851011
TI  - [Functional activity of peritoneal macrophages in acute destructive pancreatitis:
      evaluation, implication].
AB  - According to the etiology of acute pancreatitis, the authors identified the most
      common phenotypes of superficial antigens of peritoneal macrophages: CD14(+)
      CD25(-)CD64(-)HLA-DR(-) in acute biliary pancreatitis, CD14(+) CD25(+)CD64(+)HLA
      DR(+) in nonbiliary pancreatitis; moreover, all the patients were found to have
      increased expression of early (CD25+) and late (HLA-DR+) markers of cell
      activation. A comparative study was conducted and the most informative tools to
      evaluate the adhesive, cytokine-producing, phagocytic, and oxygen-dependent
      activities of peritoneal macrophages were recognized.

PMID- 21851012
TI  - [Estimation of the level of endogenous intoxication in septic infants].
AB  - The investigation was undertaken to estimate the degree of endogenous
      intoxication (EI) in septic infants, by studying the levels of circulating immune
      complexes (CIC) and leukocyte intoxication index (LII). A clinical trial was
      conducted in 46 patients with septic infants aged 1 month to 1.5 years. According
      to clinical and laboratory parameters, the author identified 3 grades of EI,
      which were directly related to the patient's condition. Despite clinical
      resolution, the levels of CIC and LII significantly remained at the high baseline
      level in 18% of the patient, which created conditions for developing
      complications and recurrences and suggested that the pathological process was
      incomplete. Therefore it is recommended to keep in mind these indicators in
      predicting sepsis and they may be extensively used in the practical health
      system.

PMID- 21851013
TI  - [Comparative evaluation of protein hydrolysates in designing their based
      universal culture medium for the diagnosis of plague and cholera].
AB  - Various protein hydrolysates made in Russia and foreign countries were
      comparatively evaluated to use them to design a universal agarized culture medium
      for the diagnosis of plague and cholera. Pancreatic baker's yeast broth was found
      to be most effective among the test media.

PMID- 21851015
TI  - [New possibilities of complex monitoring of the cardiovascular system during
      thoraco-abdominal surgeries].
AB  - The aim of the study was to compare effectiveness of combined cardiovascular
      monitoring in assessment of quality of anesthetic protection during combined
      general anesthesia with thoracic level epidural analgesia during thoraco
      abdominal surgeries. The study included 56 patients (ASA II-IV). The preoperative
      examination consisted off: ECG (rest), ECG (stress), 24 hour ECG monitoring. The
      intraoperative hemodynamic parameters (BPsist., BPdiast., BPmed., HR) were
      monitored both by invasive and non-invasive methods. Using the measurements of
      cardiac output (extrasternal dopler) the cardiac index, specific peripheral
      vascular resistance and stroke index were calculated. During intra and
      postoperative period (1st and 5th day) ECG monitoring was made. The received data
      was compared according to the following parameters: character of rhythm,
      circadian index, supraventricular and ventricular ectopic activity, dynamics of
      the ST segment. The results show that inclusion of thoracic epidural blockade
      combined with general or total intravenous anesthesia during thoraco-abdominal
      surgeries is accompanied by more favorable hemodynamic restructuring, heart rate
      stability and well expressed anti-ischemic effect. Thus, inclusion of modern
      combined cardiovascular monitoring methods during anesthesia widens the
      diagnostic abilities and noticeably increases the patient safety during high risk
      surgeries.

PMID- 21851016
TI  - [Central venous blood oxygen saturation and venous to arterial PCO2 difference
      after combined heart valve surgery].
AB  - The aim of our study was to investigate the relationship between central venous
      oxygen saturation (ScvO2) and venous-to-arterial difference in PCO2 (Pv-aCO2) and
      their role in the assessment of balance between oxygen delivery and consumption
      after combined valve surgery. The prospective observation study included 38 adult
      patients with acquired valvular hear diseases, requiring surgical correction of
      two or more valves using cardiopulmonary bypass. All patients were divided into 2
      groups according to the central value of central venous oxygen saturation
      (ScvO2): low ScvO2 (ScvO2 < 70%) and high ScvO2 (ScvO2 > 70%). In both groups
      blood gases, Pv-aCO2, lactate concentration, hemodynamic parameters, cardiac
      index, oxygen delivery and oxygen consumption were assessed. During the
      postoperative period there was a decrease of ScvO2 < 70% in 26% of patients which
      was accompanied by increased Pv-aCO2 > 5 mmHg and by risen oxygen consumption. We
      observed a moderate correlation between ScvO2 and Pv-aCO2 during the early
      postoperative period: at the end of surgery, 6 and 12 hours after it (rho = 
      0.53; -0.62 and -0.43 respectively, n = 38, p < 0.01). The changes in ScvO2 and
      Pv-aCO2 regressed after 24 hours in ICU. Thus, decreased ScvO2 and increased Pv
      aCO2 after combined valve surgery are related and reflect the rise in oxygen
      consumption.

PMID- 21851017
TI  - [The algorith of preoperative cardiovascular therapy in high risk elderly
      oncology patients].
AB  - The study was based on 478 oncology patients (72.1 +/- 3.6 years old) with
      cardiovascular comorbidities operated from 1991 to 2008 in regards of abdominal
      and pelvic mainly 3rd stage tumors with multimodal general anesthesia (4.2 +/-
      1.6 hours). In prospective group (n = 302) all patients received cardiovascular
      treatment, while in retrospective group (n = 176) only 48.9% received it. The
      evaluation of the cardiovascular therapy effect was based on the peri-operative
      and postoperative HR and BP dynamics. The occurrance of noticeable bradycardia
      and drop of BP lower than 90/60 mm Hg was considered as a deviation. It is
      revealed that the cardiovascular therapy with beta adrenoblockers and calcium
      antagonists leads to an intraoperative bradycardia in 59.8% and 73.7% of cases,
      while in patients without the aforementioned therapy in 26.6% and 46.4% of cases
      respectively (p < 0.05). Antiarrhythmics don't have a noticeable impact on the
      development of bradycardia (p = 0.204). Intraoperative hypotension on the basis
      of ATP inhibitor treatment developed in 92.2% of patients statistically
      significant (p < 0.01). Monotherapy with calcium antagonists or nitrates leads to
      the development of hypotension in 55.2% and 41.4% of cases respectively, though
      in patients without the given therapy a lot more often (p < 0.05). In the case of
      combined calcium antagonist/nitrate therapy hypotension develops in 55.5% of
      cases, and in 72.3% without the therapy (p < 0.05). For the means of prevention
      of cardiovascular complications during the surgical treatment it is appropriate
      to keep the therapy with nitrates, though vasodilatives should be canceled 12
      hours before the surgery.

PMID- 21851018
TI  - [The use of tranexamic acid during large joint endoprosthetic surgeries].
AB  - The aim of the study is to measure the effectiveness and safety of tranexam acid
      during hip and knee joint endoprothesis surgeries. Tranexam (Mir-Pharm, Russia)
      was administered to 45 patients 30 minutes before the surgery in the dose of 10
      15 mg/kg and 6 hours after first infusion in the same dose. In the control group
      (n = 45) Tranexam was not administered. The intraoperative, drain and general
      blood loss, need of donor blood and dynamics of hematological parameters were
      assessed. The total number of complications and potential transfusion
      complications was measured. The use of Tranexam acid allowed lowering the blood
      loss on all the stages of investigation for more than 50%. The general blood loss
      in the main group was 693.3 +/- 252.2 ml compared to 1259 +/- 454.6 ml in the
      control group. A need for donor erythrocytes occurred in 2 cases of the main
      group, who received the total of 3 doses of allogenic blood. In the control group
      26 patients received 57 doses of donor blood. There was no need in donor plasma
      in the main group. The hemoglobin and hematocrit values were higher in the main
      group compared to the control group. In both cases there were no tromboembolic or
      transfusional complications. The potential risk of transfusional complications
      was lower in the main group. Tranexam acid is an effective and safe blood loss
      prophylaxis measure during the large joint prosthetic surgeries.

PMID- 21851019
TI  - [Realization of Fast track surgery principles during cesarean section].
AB  - The aim of the study was to evaluate the efficiency of Fast Track Surgery (FTS)
      program application and determine the role of the anesthesiologist in its
      realization during planned Cesarean section. There were 2 randomized groups
      formed (basic and control), which contained 22 patients each. The groups were
      identical by all anthropometrical indicators. The FTS was applied in the basic
      group while the control group was led in traditional postoperative mode. The
      level of postoperative pain was estimated by Visual Analogue Scale (VAS) in rest
      and during cough 6, 12 and 24 hours after surgery, cortisol and glucose level
      dynamics, Baevskiy index, nausea and vomiting frequency, defecation and urination
      delay, presence of anxiety and weakness were assessed. The VAS and Baevskiy index
      were lower in the basic group during 12th and 24th hour of investigation, p <
      0.05. There was no difference in dynamic cortisol levels in both groups. The
      values of cortisol levels didn't exceed those of presurgical levels. The tendency
      of hypoglycemia in control group that testified the prevalence of ketabolic
      proccesses was accompanied by weakness and orthostatic reactions. In both groups
      urination delay, nausea and vomiting were present. The obtained data proved the
      efficacy and safety of FTS during Cesarean section. The study shows that the
      decision of FTS has to be made by the anesthesiologist. It can improve
      perioperative conduction of patients and result in the promt stabilization of
      mother's condition after surgical intervention and result to the optimized
      contact with the child as well as reduce the period of hospital stay and decrease
      the expenses.

PMID- 21851020
TI  - [Caudal anesthesia and its determinant factors].
AB  - In 130 surgical patients with diseases and injuries in the area of the perineum
      and lower extremities the clinical effects of three modern local anesthetics: 2%
      solution of lidocaine, 0.5% solution of bupivacaine, 0.75% solution of
      ropivacaine and their combinations (2% lidocaine and 0.25% bupivacaine solution
      2% lidocaine and ropivacaine 0.375% solution) were followed with regard to the
      influence of increasing volumes of local anesthetics and different rates of drug
      administration. It is established that an effective caudal anesthesia is provided
      with all modern local anesthetics, with increasing use of local anesthetic
      solution to 40 ml provides duration and the prevalence of sensory and motor
      blocks, the use of mixture of local anesthetics optimizes the development and
      maintenance of the caudal blockade.

PMID- 21851021
TI  - [EEG and bispectral analysis during inhalational anesthesia in children].
AB  - Bispectral index (BIS) is a parameter of the depth of anesthesia, but the use of
      it in children remains discussable. The study was carried out to compare EEG and
      BIS considering the age of patients during anesthesia with halotane, sevoflurane
      and consequent combination of sevoflurane and isoflurane. 60 children 3 to 17
      years of age, who underwent urological surgeries, were divided into 3 groups (20
      patients in each): 1st--halothane group, 2nd--sevoflurane group and 3rd-
      consequent combination of sevodlurane and isoflurane group. The oxygen: nitrous
      oxide 1:1 mixture was used in all the mentioned groups. EEG recording (6 channel
      computerised encephalograph) and BIS monitoring (XP version) was carried out
      through the whole duration of anesthesia. In the 1st group the gradual reduction
      of main rhythm was registered on EEG, with slow activity and restoration during
      awakening. The BIS index values changed from 95-98 to 39-47 with rise to 77-85
      during awakening. In the 2nd and 3rd group where sevoflurane was used for
      anesthesia induction sharpened alpha rhythms, amplitude enlargement and rhythm
      synchronization were registered on EEG. BIS values changed from 96-99 to 13-38.
      During the maintenance of anesthesia in the 2nd group BIS values were 30-40 and
      72-77 during awakening. In the stage of isoflurane anesthesia in the 3rd group
      EEG pattern changed towards the rhythm synchronization and slow oscillations in
      all the leads. The BIS index was 30-39 during maintenance and 70-76 during
      awakening. The parameters of EEG and BIS in all the investigated groups were
      proportional to the clinical stage and depth of anesthesia. Based on the clinical
      data and its comparison to EEG and BIS values it is determined that BIS index can
      be used for monitoring depth of anesthesia in children.

PMID- 21851022
TI  - [Evaluating the effectiveness of "open lung" maneuvre].
AB  - The purpose of this study--a comparative evaluation of the treatment of
      postoperative acute respiratory insufficiency in cardio surgical patients with
      lung opening maneuver and conventional mechanical ventilation. The study included
      81 patients operated on the heart and magistral vessels in which the immediate
      postoperative period was complicated by the development of acute lung injury.
      Patients were divided into 2 groups: 1 (main) group (48 patients), on which the
      open lung technique was used, 2 (control) group (33 patients) who underwent a
      standard respiratory support. The initial values of the partial oxygen pressure
      in arterial blood and the oxygenation index in patients of both groups were
      significantly reduced, and the fraction of intrapulmonary shunting -
      significantly increased. Starting with 1 day sharp increase in PaO2 and IE in
      patients with the first group was noticed, which coincides with the beginning of
      the opening of the alveoli. At the same time, the dynamics of these indicators in
      the second group had the reverse tendency. After the recruiting maneuver in all
      patients significant improvements in the mechanics of breathing were noticed. As
      a result of the recruiting maneuver in the first group sustained improvement of
      arterial oxygenation was achieved in 35 patients. In patients with acute
      postoperative respiratory failure recruiting maneuver led to a significant
      increase in arterial oxygenation and reduce the fraction of intrapulmonary shunt.
      Application of "open lung" maneuver leads to the resolution of respiratory
      failure, which greatly reduces the timing of mechanical ventilation and length of
      stay of patients in intensive care units in comparison with traditional methods
      of respiratory therapy.

PMID- 21851023
TI  - [Assessment of cardiac output and intrathoracic blood volume by means of
      transpulmonary thermodilution and ultrasound dilution: similarities and
      differences].
AB  - The aim of the study is to compare results of the assessment of cardiac output
      and intrathoracic blood volume by two methods--transpulmonary (TTD) and
      ultrasound (UTD) thermodilution. MATERIALS AND METHODS: The prospective study
      included 58 patients (sepsis, septic shock, acute respiratory distress syndrome,
      intracranial haemorrhages), which underwent femoral artery catheterization with
      "Pulsiocath" 5Fr catheter (PICCO technology). For the means of ultrasound the
      catheter was connected to the central venous catheter by an arteriovenous loop.
      Sensors on arterial and venous ends of the loop registered the time and the
      volume of the indicator, blood properties and the ultrasound curve. Cooled (0 to
      8 C) 5% glucose solution was used as an indicator for TTD, while heated (up to
      37C) 0.9% NaCl solution was used as an indicator for the ultrasound. The cardiac
      output (CO) was measured by TTD and UTD, the global end diastolic volume (GEDV)
      by TTD, its analogue total end diastolic volume (TEDV) by UTD, intrathoracic
      blood volume (ITBV) by TTD and central blood volume (CBV) by UTD. 218 pairs of
      measurements were conducted. Oscillations of CO (TTD) were 2.76-16.3 l/min (8.6
      +/- 2.48 l/min) and of CO (UTD)--2.92-18.1 l/min (8.72 +/- 2.65 l/min). There was
      a strong correlation between CO (TTD) and CO (UTD). The systematic mistake was
      0.12 l/min, percentage based mistake--20.9%. ITBV correlated with CBV. There was
      a big systematic mistake found, which measured as much as 323 ml, the percentage
      based mistake was 36.5%. The correlation between GEDV and TEDV was (r = 0.70, p <
      0.01). The TTD ejection fraction (23.2 +/- 5.6%) was lower (p < 0.01), than by
      UTD (57.8 +/- 15.2%). RESULTS: Both methods demonstrate close values of CO. GEDV
      was higher than TEDV and physiological heart volume. The absolute values of GEDV
      and ITBV measured by TTD are higher than the actual ones, although they reflect
      the changes of blood volume and can be used as dynamic preload parameters.

PMID- 21851024
TI  - [Permanent venovenous hemofiltration in the complex therapy of severe acute
      pancreatitis].
AB  - Regardless of modern achievements in intensive therapy the mortality from severe
      acute pancreatitis progressed to a polyorganic insufficiency reaches 60%.
      Analysis of mortality structures shows that more than 50% of patients die from
      severe acute pancreatitis in first 72 hours, which is indicated as early severe
      pancreatitis. In the recent years the experimental and clinical studies proved
      that continuous vein to vein hemifiltration in the early stage allowes to lower
      the severity of poliorgan insufficiency and early death. The aim of the study was
      to measure the efficiency of vein to vein hemifiltration in the complex treatment
      of early severe acute pancreatitis. The retrospective analysis consisted of 106
      patients, which were divided into 2 groups. 1st with vein to vein hemifiltration
      in the dose of less than 30ml/kg/h (n = 45) and more than 30 ml/kg/h (n = 20)
      respectively, the 3rd group did not receive vein to vein hemifiltration (n = 41).
      The study showed the decrease of early mortality (14 days) in the 2nd group (p =
      0.022) and a tendency of decrease in the 2nd group (p = 0.093) compared to the
      3rd group. The median interval from admission to death in the first two groups
      was 14 days while in the 3rd group it was only 5 days. The use of vein to vein
      hemifiltration in complex therapy of early severe acute pancreatitis patients
      allows to lower the early mortality. The best results were reached in the 2nd
      group.

PMID- 21851025
TI  - [Clinical effectiveness of the infusion therapy under control of the
      transesophageal dopplerography in acute period of severe combined trauma].
AB  - In 72 patients with combined trauma the impact of volume and consistence of
      infusion therapy on severity of the disease, frequency and severity of infectious
      complications, duration of MV and ICU stay was assessed. The patients were
      divided into 2 groups depending on the volemic status control method and infusion
      algorithm. The main group (35 patients) was controlled by transesophageal
      dopplerography Cardio Q apparatus ("Deltex Medical", GB) and the infusion therapy
      was carried out under the control of stroke volume and Ftc. In the control group
      (37 patients) the volemic status was assessed clinically: BP, CVP, HR, diuresis.
      The volume of the infusion therapy during the first 12 hours in the main group
      was significantly higher than in the control group which proved that patients
      were suffering from hypovolemia, which was not diagnosed by traditional clinical
      criteria. The ICU stay in the main group was significantly shorter compared to
      the control group 15.3 +/- 8.2 and 29.5 +/- 10.4 days respectively. Infectious
      complications occurred in 12 patients out of 35 in main group and 25 out of 37 in
      the control group. The conclusion of this study is that infusion therapy control
      with central hemodynamic parameters can shorten the MV time and ICU stay an lower
      the rate of infectious complications in patients with combined trauma. A
      mortality decrease in patients with transesophageal dopplerography controlled
      infusion is not shown.

PMID- 21851026
TI  - [Post-monitoring changes in zero drift of "Codman" intracranial pressure
      sensors].
AB  - The purpose of the study was to estimate the drift of the zero value of "Codman"
      intracranial pressure sensors, compared with the duration of monitoring, location
      of intracranial pressure sensors, and also to assess the relationship of drift to
      the gauge number. 60 "Codman" intracranial pressure sensors were investigated.
      The analysis of zero drift were made depending on the length of monitoring and
      location of the intracranial pressure sensor, as well as on description of the
      gauge number. Data are presented as median, quartiles, minimum and maximum
      values. The gauge numbers of 499, 491 and 501, (475 and 513). The drift was 0 mm
      Hg. -1 And 0 (-2 to 3). In 43% of the ICP measurements of the drift of the zero
      value was absent. In 40% o the drift was within +/ - 1 mm Hg. The analysis showed
      no dependence of the drift of the zero value of the duration of monitoring,
      location of the sensor and gauge numbers. On two patients simultaneous recording
      of intracranial pressure in the ventricles and brain parenchyma was carried out.
      The high correlation between the measured values r = 0.94, p < 0.01. In one "in
      vivo" case the zero drift was detected, which amounted to 2 mm Hg and grew by 5th
      day of monitoring. The maximum value of the drift of the zero value was 3 mm Hg.
      The dependence of drift on the duration of monitoring, reference values of the
      calibration and sensor implant site was absent. This shows the accuracy and
      reliability of parenchymal ICP measurement.

PMID- 21851027
TI  - [Effect of adrenaline on the quality of postoperative epidural analgesia].
AB  - The aim of the study was to assess the efficacy and safety of patent controlled
      analgesia (PCEA) combining opioid-local anesthetic mixture and adrenaline
      administered after thoracotomy and laparotomy. 164 adult patients after major
      thoracic and abdominal surgery were enrolled in prospective randomized study. All
      patients were given PCEA using 0.125% bupivacaine and fentanyl (2 mcg/ml) eithr
      without (BF group, n = 73) or with adrenaline (2 mcg/ml) (ABF group, n = 91).
      Pain scores were assessed in rest and coughing by 100-point visual analog scale
      (VAS) at 3, 6, 12 and 24 hours after ICU admission. In addition, the consumption
      of medication and the incidence of adverse effects (pruritis, urine retention,
      and nausea/vomiting) were recorded. Data were compared by the means of Student's
      t-test and chi2 test. p < 0.05 was regarded as statistically significant. VAS in
      coughing was significantly lower in the ABF group at 3rd 6th 12th, 18th and 24th
      hour after ICU admission. The consumption of medication requested for the
      adequate analgesia (VAS < 3) decreased in the ABF group compare to the BF group.
      The number of incidence of side effects was lower in the ABF group. The outcome
      of the study shows that use of PCEA with bupivacaine--fentanyl mixture with
      adrenaline after major surgery reduces the consumption of both bupivacaine and
      fentanyl and lowers the incidence of adverse effects, therefore improving the
      quality of analgesia.

PMID- 21851028
TI  - [Nutritional status, anesthesia and early postoperative complications in patients
      with radical operations on the esophagus].
AB  - The material of the research were 63 patients operated on benign strictures and
      esophageal cancer in the RSCS after B.V. Petrovsky. We studied the occurrence and
      the character of postoperative complications, dependence on initial nutritive
      (alimentary) status and anesthesia techniques. The main postoperative
      complications were of respiratory system and cardiovascular insufficiency and
      mainly depended on the initial degree of nutritive and used anesthesia
      techniques. No significant difference in the structure of postoperative
      complications for the patients with benign and malignant diseases of esophagus
      has been identified.

PMID- 21851029
TI  - [Xenon for postoperative analgesia: why not?].
AB  - Xenon is widely used for maintenance of anesthesia, however the analgesic effect
      of this noble gas brings to an idea of its use in analgesic schemes. The first
      time antinociceptive features of Xe were described by B. Lachman and colleagues
      in 1988. It is well known that Xe realises its analgesic potential through
      powerful non-competitive blockade of NMDA-glutamate receptors, by that
      suppressing the development of hyperalgesia process in neurons of posterior horns
      of spinal cord, which take part in the process of pain transmission and forming
      of central sensitization and becoming the actual "gates of pain". In the given
      review the literature data on mechanisms, effectiveness, safety and
      farmacoeconomic justification of the use of Xe as an analgesic in clinical
      practice are brought up.

PMID- 21851030
TI  - [Heart rhythm dysfunction in non-cardiosurgical patients].
AB  - The amount of non-cardiosurgical interventions rises every year approximately by
      1.5%. The main growth is due to the enlargement of old and elderly patients
      group. This group has the highest evidence of cardiovascular diseases. The
      frequency of sudden cardiac death and myocardial infarction after non
      cardiosurgical interventions is approximately 3.5%. The prevalence of arrhythmias
      in postoperative period reaches 20%. The issue of postoperative arrhythmias is a
      very actual problem of intensive care which needs further research. Preoperative
      arrhythmias are an independent risk factor of cardiological postoperative
      complications. The treatment by beta blockers and antiarrhythmics can lead to a
      resistant bradycardia. Different cardio stimulators are being used for the means
      of prophylaxis and treatment.

PMID- 21851031
TI  - [Malignant ovarian germ cell tumors--clinical characteristics and analysis of
      outcomes].
AB  - OBJECTIVES: Presentation of a group of patients with diagnosed malignant ovarian
      germ cell tumors (MOGCT), determination of prognostic factors and outcome
      analysis. MATERIAL AND METHODS: We selected patients with diagnosed malignant
      ovarian germ cell tumors from the patient registry of Cancer Center in Warsaw
      from 1990 to 2001. We analyzed clinical and pathological features of the study
      group, as well as methods and results of treatment. RESULTS: We collected
      documentation of 83 patients. Most were diagnosed with dysgerminoma and immature
      teratoma in the early stages of development. 73 patients received adjuvant
      chemotherapy after surgery At the end of the first line of treatment complete
      response was achieved in 63 patients (75.9%). Time to recurrence ranged from 25
      to 518 days (mean 176 days). The most common site of recurrence was the true
      pelvis. The five-year overall survival was 62.7%. Significant favorable
      prognostic factor was early stage of disease and the histological diagnosis of
      dysgerminoma. From the 46 women after fertility-sparing surgery, 8 became
      pregnant. CONCLUSIONS: MOGCT are a group of potentially curable, yet very
      aggressive malignant ovarian tumors. The main condition for obtaining good
      results is quick diagnosis and appropriate treatment, usually surgery associated
      with multidrug chemotherapy The stage of the disease remains the most important
      prognostic factor. Patients diagnosed with dysgerminoma are a separate group with
      very good prognosis.

PMID- 21851032
TI  - Application of neuron networks in the diagnostics of endometrial pathologies.
AB  - AIM: The aim of the study was to construct neuron networks utilizing selected
      risk factors and ultrasonographic (USG) examination parameters in a two
      dimensional (2D) and three-dimensional (3D) presentation in relation to
      endometrial pathologies. MATERIALS AND METHODS: The following risk factors were
      statistically analyzed: age and menopausal status, parity using hormonal
      replacement therapy (HRT), BMI, 2D USG of the endometrium (thickness, uterine
      artery blood flow indices) and 3D USG (volume, vascularization indices) in
      relation to the result of histopathological examination of the endometrial tissue
      in 421 women, aged 22-87 years, with abnormal bleeding from the uterus. The
      changes of the sensitivity and specificity in the applied models corresponding to
      changes of the limit value, were presented in the form of receiver operating
      characteristic curves (ROC) and the comparison of the values of the area under
      the curve (AUC). The threshold value for the obtained models was established and
      models of artificial neuron networks (ANN) were constructed on the basis of the
      ROC. CONCLUSION: Application of artificial neural networks in medicine has been
      developing rapidly They have been applied in pre-surgical differentiation of
      ovarian tumors and other neoplasms. In case of endometrial carcinoma the degree
      of clinical usage of artificial neural networks has been limited, despite the
      fact that, from the mathematical point of view, the differentiation using neural
      networks would be much more precise than the one that could be obtained by
      chance.

PMID- 21851033
TI  - [Expression of podoplanin in ovarian clear cell carcinoma].
AB  - INTRODUCTION: Podoplanin is a transmembrane glycoprotein expressed in endothelial
      lymphatic cells. It was proven to be a predictive marker in a variety of cancers
      e.g. mesothelioma and head and neck squamous-cell carcinoma. Ovarian clear cell
      carcinoma (OCCC) is a rare and unique histopathologic subtype of epithelial
      ovarian cancer (EOC). The molecular basis of that phenomenon remains unknown.
      OBJECTIVES: The aim of our study was to assess podoplanin expression on the
      protein level in OCCC. MATERIAL AND METHODS: Immunohistochemistry was performed
      on paraffin-embedded tissues from 19 patients with diagnosed OCCC. RESULTS:
      Podoplanin expression was present (moderate or strong) in 52% of OCCC cases
      (10/19). Nine of eleven (81.2%) postmenopausal and one of eight (12.5%)
      premenopausal women were podoplanin positive. No differences in podoplanin
      expression were found in relation to clinical features of the tumor CONCLUSION:
      The incidence of podoplanin expression is higher in ovarian clear cell
      adenocarcinoma in postmenopausal patients.

PMID- 21851034
TI  - [Changes in the concentration of sHLA-I and selected cytokines in pregnancy
      complicated by antiphospholipid syndrome].
AB  - OBJECTIVES: To compare the serum concentrations of the selected cytokines from
      subsequent trimesters of antiphospholipid syndrome complicated pregnancies.
      MATERIAL AND METHODS: This study included 43 pregnant women (23 patients
      diagnosed with antiphospholipid syndrome and 20 controls). IL-2R, IL-4, IL-10,
      INF-gamma, TNF-alpha, and class I sHLA concentrations were analyzed by ELISA in
      the 1st, 2nd and 3rd trimester RESULTS: INF-gamma levels were below the method
      detection threshold and therefore were not included in the final analysis. No
      significant changes in IL-2R, IL-4, IL-10, TNF-alpha, and class I sHLA
      concentrations were observed in subsequent trimesters in the group of women with
      antiphospholipid syndrome. Significant decrease in IL-10 in the 2nd trimester
      along with significant increase in TNF-alpha in the 3rd trimester were noted
      amongst the control subjects. The only significant inter-group difference was
      observed in the 1st trimester when mean TNF-alpha level was significantly higher
      among antiphospholipid syndrome women if compared to controls. CONCLUSIONS: The
      observed lack of significant differences between antiphospholipid syndrome
      affected and control group pregnancies in their sHLA class I and cytokine
      concentrations may be related to the fact that the treatment of antiphospholipid
      syndrome was implemented early and continued throughout all trimesters of the
      pregnancy.

PMID- 21851035
TI  - [Evaluation of vertical transmission of two species of ureaplasmas in term
      newborns without respiratory disorders--a preliminary study].
AB  - Pregnancy promotes ureaplasma vaginal colonization. This creates the possibility
      of vertical transmission of these organisms to the child. These microorganisms
      can cause complications during pregnancy and poor condition of newborn.
      OBJECTIVES: Objectives of this study were to analyze the vertical transmission of
      different species of ureaplasmas in term newborns without respiratory distress.
      MATERIALS AND METHODS: The study included 50 mothers and 50 of their newborn
      children. Swabs were obtained from swabs of the cervix in women and tracheal
      aspirates from neonates. The presence of ureaplasmas was confirmed by culture and
      PCR. Ureaplasmas species identification was performed using PCR. RESULTS:
      infection of ureaplasmas was found in 21 women (42%). Predominant species was U.
      parvum, which was found in 18 women. In 3 patients only the presence of U.
      urealyticum was confirmed. Ureaplasma infection in mother and her newborn baby
      was confirmed in 8 (17.4%) mother-child pairs, including 6 of these cases showing
      the presence of U. parvum and 2 U. urealyticum. The incidence of vertical
      transmission of ureaplasma infection was assessed at 33% for U. parvum and 67%
      for U. urealyticum, and the total for both species at 38%. It should be noted
      that in the group of 18 women infected with U.parvum, in 12 cases there was no
      transmission of infection to the child. However in 3 women infected with U.
      urealyticum 2 cases of transmission from mother to child were observed (67%).
      Although the group infected with U. urealyticum accounted for only 3 women, our
      preliminary observations may suggest that this species is probably more likely to
      be transferred from mother to child. CONCLUSIONS: Infection with U. urealyticum
      may be more frequently transferred from the genital tract of mother to child.

PMID- 21851036
TI  - [Genetic variability of endothelin-1 system in gestational hypertension and
      preeclampsia].
AB  - INTRODUCTION: Recently much attention has been focused on endothelin-1 (ET-1) and
      endothelin-1 converting enzyme (ECE-1) gene polymorphisms and connected changes
      in ET-1 concentration. Additionally these processes have been shown to be
      possibly involved in preeclampsia susceptibility. The aim of this study was to
      evaluate the correlation between ET-1 (Lys198Asn) and ECE-1 (Thr341lle) gene
      polymorphisms and the risk of gestational hypertension and preeclampsia. MATERIAL
      AND METHODS: The study group consisted of 110 hypertensive (69 with gestational
      hypertension and 41 preeclamptic) pregnant women. The control group included 150
      healthy pregnant women. The frequency of investigated polymorphisms was examined
      by polymerase chain reaction and restriction fragment length polymorphism
      (PCR/RFLP) assay RESULTS: There were no statistically significant differences in
      genotype frequencies of ET-1 Lys198Asn and ECE-1 Thr341lle gene polymorphic
      variants between hypertensive pregnant women and the control group. There were
      also no remarkable differences between GH and PE groups when compared to the
      controls. However parallel presence of both Thr341lle ECE-1 and Lys198Asn ET-1
      variant localisation showed a higher occurrence rate of ECE-1 CT/ET-1 GT
      heterozygotic genotypes in the control group (5,3%) than in the whole study or GH
      and PE groups (0.9%, 1.4% and 0.0% respectively p = ns). In preeclamptic women,
      the higher systolic blood pressure value was observed in GG Lys198Asn ET-1
      genotype carriers (180.7 mmHg) than in patients with at least one mutated T
      allele (GT and TT) (167.3 mmHg, p = ns). The lowest blood pressure level was
      connected with the mutated TT Lys198Asn ET- 1 genotype presence. CONCLUSIONS:
      Results of this study suggest lack of direct correlation of Lys198Asn ET-1 and
      Thr341lle ECE-1 gene polymorphisms with risk of gestational hypertension and
      preeclampsia in the studied population of Polish women. High prevalence of ECE-1
      CT/ET-1 GT heterozygote genotypes of both Thr341lle ECE-1 and Lys198Asn ET-1
      polymorphisms in healthy pregnant subjects compared to GH and PE groups suggests
      the protective role of mutated alleles in the development of PE. The carrier of
      mutated TT genotype of Lys198Asn ET-1 polymorphism is probably connected with
      lower systolic blood pressure level in preeclamptic women. Future studies are
      needed to establish the role of analysed polymorphisms in the etiology of
      gestational hypertension and preeclampsia.

PMID- 21851037
TI  - [Are in-utero interventions justified?--perspective of neonatologists. Part I.
      Congenital diaphragmatic hernia (CDH)].
AB  - INTRODUCTION: In-utero interventions are often perceived by parents as the only
      hope for their unborn child. Because it is neonatologists who have to deal with a
      sick newborn and sometimes unrealistic optimism of the parents after delivery we
      have taken on the task of reviewing the current knowledge concerning fetal
      surgeries from the neonatologist's perspective. In the first of three parts we
      have analyzed the data for in-utero interventions for CDH. OBJECTIVE: Our main
      objective was to evaluate available data and to ascertain whether performing
      fetal surgeries for CDH is justified. METHODS: Review of available literature on
      the subject of in-utero interventions in the fetuses with CDH was performed.
      Pubmed and Cochrane library were searched for relevant publications, in
      particular for randomized controlled trials. RESULTS: In randomized controlled
      trial (RCT), the in-utero intervention did not improve the outcome. The results
      of uncontrolled clinical trials suggest that it may be beneficial in cases with
      severe lung hypoplasia. The RCT testing the efficacy of the procedure performed
      later in pregnancy in moderately severe cases in currently under way CONCLUSIONS:
      In-utero interventions might improve survival in a carefully selected group of
      patients with CDH. However the evidence to support this claim is not strong, and
      until more data is available, in-utero interventions for CDH should only be
      performed in specialized centers as part of controlled clinical trial.

PMID- 21851038
TI  - [Pregnancy of a 47-year old woman treated by in vitro fertilization using oocyte
      from a donor (IVF-OD)].
AB  - The paper presents a case of pregnancy childbirth and postpartum of a 47-year-old
      woman with secondary infertility and obstetric history. In vitro fertilization
      with oocyte derived from a 21-year donor (IVF-OD) was performed due to premature
      ovarian failure and age of the patient. The treatment resulted in unifetal
      pregnancy complicated by among others: hypertension, cardiac problems, varicose
      veins in the lower limbs, elevated concentration of bile acids and anxiety
      neurosis. A healthy newborn was delivered at 37 hbd by cesarean section. Due to
      the development of techniques of assisted reproduction, pregnancies of
      perimenopausal women will pose a growing problem in modern obstetrics.

PMID- 21851039
TI  - [Solitary fibrous tumor of the retroperitoneum in pregnancy: case report].
AB  - Solitary fibrous tumor (SFT) is a rare, usually benign tumor Most cases occur on
      the pleura, being less frequent at other serosal sites. We present a case of a
      large retroperitoneal tumor with no accompanying clinical symptoms, which was
      detected due to apparent abdominal asymmetry in a 24-year-old woman at 16 weeks
      of gestation. The MRI scan taken at 20 weeks demonstrated a retroperitoneal mass
      measuring 25 cm in length. The tumor was surgically removed at 24 weeks of
      gestation. The final diagnosis was established on the basis of the
      anatomopathological examination supplemented by immunohistochemical phenotyping.

PMID- 21851040
TI  - [Treatment of cervical pregnancy with systemic methotrexate and KCI solution
      injection into the gestational sac--case report and review of literature].
AB  - We report a case of a 6-week cervical pregnancy successfully treated with
      systemic methotrexate and gestational sac biopsy with 15%-calcium chloride
      solution injection. Serial monitoring of human chorionic gonadotropin levels,
      combined with ultrasound examinations, confirmed spontaneous miscarriage. Applied
      treatment allowed to avoid hysterectomy and preserve the patient's fertility.

PMID- 21851041
TI  - [Recommendations of Polish Gynaecological Society regarding prevention of injury
      to birth canal and structures of uterine fundus].

PMID- 21851042
TI  - [The reconstruction of ion channels created by protein neurotoxins in bilayer
      lipid membranes as a research tool for exocytosis processes].
AB  - The direct transport of inorganic ions and much highly organized biomolecules
      across native membranes by the specific membrane proteins--ionic channels
      provides the functioning of a number of important biochemical processes like
      depolarization, Ca(2+)-release and exocytosis in nerve or muscle cells at the
      synaptic transmission. Therefore, the investigation of the structure and ion
      conducting properties for neurotoxin channels and different factors affecting
      channels themselves and neuro-muscular transmission plays an important role in
      the research of pathologies that appear in intoxicated nerve tissues. As the
      massive release of neurotransmitters resulting from toxin-induced increase in
      Ca(2+)-permeability of the nerve endings occurs after the interaction of pore
      forming neurotoxins alpha-latrotoxin, alpha- and delta-latroinsectotoxin from
      black widow spider venom with the specific receptors located on plasma membrane
      of the vertebrate or invertebrate nerve cells most attention in the review is
      paid to the reconstitution of above toxins channels. The part the pore-forming
      proteins reconstruction research takes to determine the exocytosis regulation
      endogenous cell proteins may participate has been observed on the example of
      latrotoxin-like L-protein from bovine brain nerve cells cytoplasm capable of
      binding with antibodies against alpha-latrotoxin.

PMID- 21851043
TI  - [Metabolic changes in cells under electromagnetic radiation of mobile
      communication systems].
AB  - Review is devoted to the analysis of biological effects of microwaves. The
      results of last years' researches indicated the potential risks of long-term low
      level microwaves exposure for human health. The analysis of metabolic changes in
      living cells under the exposure of microwaves from mobile communication systems
      indicates that this factor is stressful for cells. Among the reproducible effects
      of low-level microwave radiation are overexpression of heat shock proteins, an
      increase of reactive oxygen species level, an increase of intracellular Ca2+,
      damage of DNA, inhibition of DNA reparation, and induction of apoptosis.
      Extracellular-signal-regulated kinases ERK and stress-related kinases p38MAPK are
      involved in metabolic changes. Analysis of current data suggests that the concept
      of exceptionally thermal mechanism of biological effects of microwaves is not
      correct. In turn, this raises the question of the need to revaluation of modern
      electromagnetic standards based on thermal effects of non-ionizing radiation on
      biological systems.

PMID- 21851044
TI  - [Effect of cetyltrimethylammonium on the human blood cholinesterases activity].
AB  - The influence of cationic detergent cetyltrimethylammonium on the human blood
      cholinesterases activity (erythrocyte acetylcholinesterase and plasma
      butyrylcholinesterase) in reactions of hydrolysis of alpha-thionaphthylacetat and
      acetylthiocholine is studied. It is shown, that cetyltrimethylammonium is
      reversible effector for both cholinesterases. This compound competitively
      inhibited enzymatic hydrolysis of acetylthiocholine by both cholinesterases, and
      in the reactions of enzymatic hydrolysis alpha-thionaphthylacetat display as the
      synergistic activator--in experiments with butyrylcholinesterase, and as the
      reversible inhibitor--in experiments with acetylcholinesterase. Kinetic constants
      in reaction of acetylcholinesterase inhibition by cetyltrimethylammonium defined
      by means of different substrates--alpha-thionaphthylacetat and acetylthiocholin.
      They are close among themselves and amount (2.5 +/- 0.3) x 10(-5) and (2.8 +/-
      0.3) x 10(-5) M, accordingly. Butyrylcholinesterase was more sensitive to
      influence of cetyltrimethylammonium. The kinetic constants defined for this
      enzyme by the effect of inhibition of acetylthiocholin hydrolysis or activation
      of alpha-thionaphthylatcetat hydrolysis, are also close among themselves and
      amount (3.9 +/- 0.4) x 10(-6) and (4.4 +/- 0.4) x 10(-6) M, accordingly.

PMID- 21851045
TI  - [Effect of calixarene C-107 on kinetic parameters of Na+, K(+)-ATPase in the
      plasma membrane of the uterus myocytes].
AB  - The inhibitory action of calixarene C-107 (5,17-diamino(2-pyridyl)methylphosphono
      11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxy-calix[4]arene) on Na+, K(+)
      ATPase activity kinetic properties of myometrium perforated plasma membrane was
      investigated. It has been shown that the calixarene C-107 inhibiting Na+, K(+)
      ATPase does not change the kinetic parameters (Km, nH) of reaction velocity
      dependence on substrate concentration. The constant Ka of enzyme activation by
      MgCl2 has complex dependence on calixarene C-107 concentration: it increases
      twice with growth of calixarene concentration up to 50 nM and decreases to the
      control level with further growth of calixarene concentration. The Hill
      cooperativity coefficient nH of activation by MgCl2 does not vary in the presence
      of calixarene C-107. Both ATP and MgCl2 have no influence on Na+, K(+)-ATPase
      constant of inhibition by calixarene C-107, but an increase of concentration of
      the mentioned physiological compounds causes the growth of cooperativity
      coefficient nH of enzymatic reaction inhibition by calixaren C-107.

PMID- 21851046
TI  - [Activation of presynaptic ionotropic glutamate receptors stimulates GABA release
      from hippocampal and cortical nerve terminals in rats].
AB  - One of the pathways implicated in a fine-tuning control of neurosecretory process
      is the activation of presynaptic receptors. The present study was focused on the
      role of presynaptic glutamate receptor activation in the regulation of inhibitory
      synaptic transmission in the rat hippocampus and cortex. We aimed to clarify what
      types of ionotropic glutamate receptors are involved in the modulation of GABA
      secretion, and what mechanism underlies this modulation. We have revealed that
      specific agonists of kainate and NMDA receptors, kainate and NMDA, like
      glutamate, induced the release of [3H]GABA from hippocampal and cortical nerve
      terminals suggesting the involvement of both types in the regulation of GABAergic
      transmission. Our results indicate preferential involvement of vesicular, but not
      cytosolic, pool in response to glutamate receptor activation. This is based on
      the finding that NO-711 (a specific inhibitor of plasma membrane GABA
      transporters), fails to attenuate [3H]GABA release. We have concluded that
      presynaptic glutamate receptor-induced modulation of the strength of synaptic
      response is due to increasing the release probability of synaptic vesicles.

PMID- 21851047
TI  - [Exocytotic steps in cell-free system after cholesterol deprivation in
      synaptosomal plasma membranes and synaptic vesicles].
AB  - Using a cell-free system we investigated a specific role of cholesterol in
      exocytotic processes. To modulate the cholesterol content in membrane methyl-beta
      cyclodextrin was used as a cholesterol binding agent. The experimental conditions
      for cholesterol depletion from synaptosomal membrane structures were determined
      and depended on methyl-beta-cyclodextrin concentration, time and mediums
      temperature. The role of cholesterol was studied on the stages of synaptic
      vesicles docking and Ca(2+)-stimulated fusion which are the components of
      multivesicular compound exocytosis. Using dynamic light scattering technique we
      have found that after cholesterol depletion from synaptic vesicles the process of
      their aggregation (docking) remains unchanged. It was found that the rate of
      calcium-triggered fusion of synaptic vesicles depends on the membrane level of
      cholesterol. The decreasing level of synaptosomal plasma membrane cholesterol by
      8% leads to suppression of the Ca(2+)-dependent membrane fusion with synaptic
      vesicles. But, under 25% reduction of plasma membrane cholesterol the level of
      membrane merging with synaptic vesicles did not differ from control; probably
      this is due to changes in physical properties of lipid bilayer and/ or
      disturbances in function of membrane proteins driving this process. In
      cholesterol depleted synaptosomes the exocytotic release of glutamate stimulated
      by calcium was decreased by 32%. Obtained data suggest that the cholesterol
      concenration in synaptosomal plasma membranes or synaptic vesicles is the crucial
      determinant for synaptic transmission efficiency in nerve terminals.

PMID- 21851048
TI  - [Design of transcription inhibitors on the basis of n-arylamides of 9-methyl- and
      9-methoxyphenazine-1-carboxylic acids].
AB  - A convenient method of synthesis was developed and two series of N-arylamides of
      9-methyl- and 9-methoxyphenazine-1-carboxylic acids were obtained. By the
      molecular docking method the mode of the synthesized compounds interaction with
      catalytic pocket of the RNA polymerase T7 transcription complex was simulated.
      Key ligand-receptor intermolecular contacts were identified. They are realized by
      various types of non-covalent interactions with line of conservative amino acid
      residues involved in recognition of incoming nucleotide, catalytic act of RNA
      synthesis as well as in stabilizing the RNA-DNA hybrid at early steps of
      transcription. In silico data indicate sufficient affinity of ligands for the
      receptor and allow to predict their ability to inhibit the functioning of RNA
      polymerase T7 transcription complex that is consistent with preliminary
      experimental results. Initial testing in a model RNA polymerase T7 transcription
      system demonstrates significant inhibition of in vitro RNA synthesis by
      investigated compounds at a concentration of 25 microg/ml (approximately 80
      microM).

PMID- 21851049
TI  - [Conformational capacity of 2',3'-didehydro-2',3'-dideoxyadenosine as a key to
      understanding its biological activity: results of quantum chemical modelling].
AB  - Comprehensive conformational analysis of the biologically active nucleoside 2',3'
      didehydro-2',3'-dideoxyadenosine (d4A) has been performed at the MP2/6
      311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and
      polar characteristics of twenty one d4A conformers as well as their
      conformational equilibrium were investigated. The electron density topological
      analysis allowed us to establish that the d4A molecule is stabilized by eight
      types of intramolecular interactions: O5'H...N3, O5'H...C8, C8H...O5', C2'H...N3,
      C5'H1...N3, C5'H2...N3 Ta C8H...H1/2C5'. The obtained results of conformational
      analysis lead us to think that d4A may be a terminator of the DNA chain sythesis
      in the 5'-3' direction. Thus it can be inferred that d4A competes with canonical
      2'-deoxyadenosine in binding an active site of the corresponding enzyme.

PMID- 21851050
TI  - [Antioxidant system activation in rats with experimental cirrhosis after
      injection of cryopreserved fetal liver cells].
AB  - The possibility to recover the antioxidant system in rats with experimental liver
      cirrhosis (LC) after allo- and xenotransplantation of cryopreserved fetal liver
      cells (FLC) was investigated. It was shown that the content of lipid peroxidation
      products in the blood serum of animals with LC four weeks after FLC
      transplantation decreased significantly as compared to control group. Such
      changes were accompanied by a significant increase of catalase (CAT), glutathione
      reductase (GR), Se-dependent glutathione peroxidase (GP) activity in the liver
      and total anti-oxidative activity (AOA) of blood. Obtained results demonstrate
      that the main direction of FLC effects in animals with LC agree with that we
      observed previously in other experimental models (partial hepatectomy, chronic
      alcohol poisoning and hypercholesterolemia). In conclusion, cell therapy may be
      considered as the universal method for correction of disorders in regulation of
      free-radical processes in various experimental pathologies.

PMID- 21851051
TI  - [Asbestos-stimulated changes in nitric oxide and iron metabolism in rats].
AB  - Under intratracheal asbestos fibers installation it has been investigated NO
      synthesis in the lung and liver tissues of Wistar rats by EPR method. Asbestos A6
      45, sifted through the sieve with size 0.1 mm, has been administrated in a dose
      of 5 mg/kg. To evaluate the NO synthesis EPR and NO-trap methods have been used.
      The amplitude of EPR signal "trap-NO" in the lung samples was 12, 16 and 14 times
      greater than in controls on the 3th, 6th and 10th days after asbestos
      installation and was corresponding to NO rate of about 2 mkmol/(g x h). In the
      liver samples of asbestos-stimulated animals the NO level contained in the non
      heme iron nitrosyl complexes was about 2 mkmol/g. Thus, the asbestos fibers
      stimulate NO synthesis not only in the lung tissue, but also in other organs. The
      obtained data shows that under NO hyperproduction certain changes in iron
      metabolism take place, such as: the decrease of transferrin iron and the
      accumulation of ferric iron not bound with transferrin. The accumulation of
      ferric iron not shielded by proteins is one of the oxidative stress triggers.

PMID- 21851052
TI  - [Development of scientific research in neurochemistry at the Institute of
      Biochemistry of the Academy of Sciences of URSR in 1941-1972. Investigation of
      carbohydrate metabolism in the brain].

PMID- 21851053
TI  - Semipinacol rearrangement in natural product synthesis.

PMID- 21851054
TI  - Asymmetric strecker reactions.

PMID- 21851056
TI  - Group 13 Lewis acid adducts of [PCl2N]3.
AB  - Phosphazene polymers are classically synthesized by the high-temperature, ring
      opening polymerization (ROP) of [PCl(2)N](3) to give [PCl(2)N](n), followed by
      functionalization of [PCl(2)N](n) with different side groups. We investigated the
      interactions of [PCl(2)N](3) with Lewis acids because Lewis acids have been used
      to induce the high-temperature ROP of [PCl(2)N](3). The reactions of [PCl(2)N](3)
      with MX(3) (M = group 13, X = halides), under strict anaerobic conditions gave
      adducts [PCl(2)N](3).MX(3). Adducts were characterized by X-ray crystallography
      and multinuclear and variable-temperature NMR studies, and mechanistic
      understanding of their fluxional behavior in solution was achieved. The
      properties of the [PCl(2)N](3).MX(3) adducts at or near room temperature strongly
      suggests that such adducts are not involved directly as intermediates in the high
      temperature ROP of [PCl(2)N](3).

PMID- 21851055
TI  - Online nanoflow reversed phase-strong anion exchange-reversed phase liquid
      chromatography-tandem mass spectrometry platform for efficient and in-depth
      proteome sequence analysis of complex organisms.
AB  - The dynamic range of protein expression in complex organisms coupled with the
      stochastic nature of discovery-driven tandem mass spectrometry (MS/MS) analysis
      continues to impede comprehensive sequence analysis and often provides only
      limited information for low-abundance proteins. High-performance fractionation of
      proteins or peptides prior to mass spectrometry analysis can mitigate these
      effects, though achieving an optimal combination of automation, reproducibility,
      separation peak capacity, and sample yield remains a significant challenge. Here
      we demonstrate an automated nanoflow 3-D liquid chromatography (LC)-MS/MS
      platform based on high-pH reversed phase (RP), strong anion exchange (SAX), and
      low-pH reversed phase (RP) separation stages for analysis of complex proteomes.
      We observed that RP-SAX-RP outperformed RP-RP for analysis of tryptic peptides
      derived from Escherichia coli and enabled identification of proteins present at a
      level of 50 copies per cell in Saccharomyces cerevisiae, corresponding to an
      estimated detection limit of 500 amol, from 40 MUg of total lysate on a low
      resolution 3-D ion trap mass spectrometer. A similar study performed on a LTQ
      Orbitrap yielded over 4000 unique proteins from 5 MUg of total yeast lysate
      analyzed in a single, 101 fraction RP-SAX-RP LC-MS/MS acquisition, providing an
      estimated detection limit of 65 amol for proteins expressed at 50 copies per
      cell.

PMID- 21851057
TI  - 3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands.
AB  - Histone-lysine acetylation is a vital chromatin post-translational modification
      involved in the epigenetic regulation of gene transcription. Bromodomains bind
      acetylated lysines, acting as readers of the histone-acetylation code.
      Competitive inhibitors of this interaction have antiproliferative and anti
      inflammatory properties. With 57 distinct bromodomains known, the discovery of
      subtype-selective inhibitors of the histone-bromodomain interaction is of great
      importance. We have identified the 3,5-dimethylisoxazole moiety as a novel acetyl
      lysine bioisostere, which displaces acetylated histone-mimicking peptides from
      bromodomains. Using X-ray crystallographic analysis, we have determined the
      interactions responsible for the activity and selectivity of 4-substituted 3,5
      dimethylisoxazoles against a selection of phylogenetically diverse bromodomains.
      By exploiting these interactions, we have developed compound 4d, which has IC(50)
      values of <5 MUM for the bromodomain-containing proteins BRD2(1) and BRD4(1).
      These compounds are promising leads for the further development of selective
      probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP
      bromodomains.

PMID- 21851059
TI  - Controlling the motion and placement of micrometer-sized metal particles using
      patterned polymer brush surfaces.
AB  - In this paper, we show that silicon surfaces patterned with poly(methacrylic
      acid) brushes are able to control the Brownian motion of 2-3 MUm iron particles,
      which sediment onto the surface in aqueous solution and experience differences in
      repulsive force depending upon their position. Differences in repulsion lead to
      different gravitational potential energies across the surface, which gives bias
      to the Brownian motion taking place. Three regimes have been identified depending
      upon the brush height: (i) no control of Brownian motion when the brush height is
      small, (ii) Brownian motion that is influenced by the polymer brush when the
      brush 17 height is intermediate, (iii) Brownian motion that is confined by
      polymer brush barriers when the brush height is greatest. The height of brush
      found necessary to significantly influence iron particle motion was small at 39
      nm or 2% of the particle diameter.

PMID- 21851060
TI  - Catastrophic vs gradual collapse of thin-walled nanocrystalline Ni hollow
      cylinders as building blocks of microlattice structures.
AB  - Lightweight yet stiff and strong lattice structures are attractive for various
      engineering applications, such as cores of sandwich shells and components
      designed for impact mitigation. Recent breakthroughs in manufacturing enable
      efficient fabrication of hierarchically architected microlattices, with
      dimensional control spanning seven orders of magnitude in length scale. These
      materials have the potential to exploit desirable nanoscale-size effects in a
      macroscopic structure, as long as their mechanical behavior at each appropriate
      scale - nano, micro, and macro levels - is properly understood. In this letter,
      we report the nanomechanical response of individual microlattice members. We show
      that hollow nanocrystalline Ni cylinders differing only in wall thicknesses, 500
      and 150 nm, exhibit strikingly different collapse modes: the 500 nm sample
      collapses in a brittle manner, via a single strain burst, while the 150 nm sample
      shows a gradual collapse, via a series of small and discrete strain bursts.
      Further, compressive strength in 150 nm sample is 99.2% lower than predicted by
      shell buckling theory, likely due to localized buckling and fracture events
      observed during in situ compression experiments. We attribute this difference to
      the size-induced transition in deformation behavior, unique to nanoscale, and
      discuss it in the framework of "size effects" in crystalline strength.

PMID- 21851058
TI  - Lactam constraints provide insights into the receptor-bound conformation of
      secretin and stabilize a receptor antagonist.
AB  - The natural ligands for family B G protein-coupled receptors are moderate-length
      linear peptides having diffuse pharmacophores. The amino-terminal regions of
      these ligands are critical for biological activity, with their amino-terminal
      truncation leading to production of orthosteric antagonists. The carboxyl
      terminal regions of these peptides are thought to occupy a ligand-binding cleft
      within the disulfide-bonded amino-terminal domains of these receptors, with the
      peptides in amphipathic helical conformations. In this work, we have
      characterized the binding and activity of a series of 11 truncated and lactam
      constrained secretin(5-27) analogues at the prototypic member of this family, the
      secretin receptor. One peptide in this series with lactam connecting residues 16
      and 20 [c[E(16),K(20)][Y(10)]sec(5-27)] improved the binding affinity of its
      unconstrained parental peptide 22-fold while retaining the absence of endogenous
      biological activity and competitive antagonist characteristics. Homology modeling
      with molecular mechanics and molecular dynamics simulations established that this
      constrained peptide occupies the ligand-binding cleft in an orientation similar
      to that of natural full-length secretin and provided insights into why this
      peptide was more effective than other truncated conformationally constrained
      peptides in the series. This lactam bridge is believed to stabilize an extended
      alpha-helical conformation of this peptide while in solution and not to interfere
      with critical residue-residue approximations while docked to the receptor.

PMID- 21851061
TI  - Frequency upshift in BO2 and CO2+ upon electronic excitation: a twin-state model
      rationalization.
AB  - The twin-state model, previously shown to provide a simple physical
      rationalization for the frequency upshift (exaltation) of the Kekule mode in
      benzene upon S(0) to S(1) electronic excitation, is extended to the case of the
      BO(2) radical and the CO(2)(+) radical cation. In the case of BO(2)/CO(2)(+), the
      ground and excited states are degenerate, yet the model applies to the degenerate
      two-state system as well. In contrast with a pseudo-Jahn-Teller model, the twin
      state one can predict which frequency is exalted and also which pair of
      electronic states are coupled, thus explaining the specificity of the phenomenon.
      The frequency exaltation is a spectroscopic manifestation of the resonance
      between the pair of VB structures describing twin states. In analogy with the
      case of benzene, it is predicted that the nu(3) asymmetric stretch fundamental
      will be a dominant peak in the two-photon absorption spectrum of BO(2) and
      CO(2)(+).

PMID- 21851062
TI  - Identification and characterization of unique tumoricidal genes in rat umbilical
      cord matrix stem cells.
AB  - Rat umbilical cord matrix stem cells (UCMSC) have been shown to exhibit a
      remarkable ability to control rat mammary adenocarcinoma (Mat B III) cell
      proliferation both in vivo and in vitro. To study the underlying mechanisms and
      genes involved in Mat B III growth attenuation, total RNA was extracted from the
      naive rat UCMSC alone and those cocultured with Mat B III in Transwell culture
      dishes. Gene expression profiles of naive rat UCMSC alone and those cocultured
      with Mat B III cells were investigated by microarray analysis using an Illumina
      RatRef-12 Expression BeadChip. The comparison of gene expression profiles between
      untreated and cocultured rat UCMSC identified five upregulated candidate genes
      (follistatin (FST), sulfatase1 (SULF-1), glucose phosphate isomerase (GPI), HtrA
      serine peptidase (HTRA1), and adipocyte differentiation-related protein (ADRP))
      and two downregulated candidate genes (transforming growth factor, beta-induced,
      68 kDa (TGFbetaI) and podoplanin (PDPN)) based upon the following screening
      criteria: (1) expression of the candidate genes should show at least a 1.5-fold
      change in rat UCMSC cocultured with Mat B III cells; (2) candidate genes encode
      secretory proteins; and (3) they encode cell growth-related proteins. Following
      confirmation of gene expression by real-time PCR, ADRP, SULF-1 and GPI were
      selected for further analysis. Addition of specific neutralizing antibodies
      against these three gene products or addition of gene-specific siRNA's
      individually in cocultures of 1:20 rat UCMSC:Mat B III cells significantly
      increased cell proliferation, implying that these gene products are produced
      under the cocultured condition and functionally attenuate cell growth.
      Immunoprecipitation followed by Western blot analysis demonstrated that these
      proteins are indeed secreted into the culture medium. Individual overexpression
      of these three genes in rat UCMSC significantly enhanced UCMSC-dependent
      inhibition of cell proliferation in coculture. These results suggest that ADRP,
      SULF-1 and GPI act as tumor suppressor genes, and these genes might be involved
      in rat UCMSC-dependent growth attenuation of rat mammary tumors.

PMID- 21851063
TI  - Lipid markers of "geometrical" radical stress: synthesis of monotrans cholesteryl
      ester isomers and detection in human plasma.
AB  - Heteroatom-centered free radicals are able to transform cis unsaturated fatty
      acids to the thermodynamically more stable, but unnatural, trans configuration.
      The "geometrical" radical stress can be estimated in biological samples using
      trans fatty acid isomers as lipid markers. Regioselectivity is an important
      feature of the "geometrical" radical stress, because the supramolecular
      organization of the polyunsaturated fatty acid moieties of phospholipids can lead
      to preferential monotrans isomer formation. The regioisomer recognition is a
      crucial step, which is helped by appropriate molecular libraries available
      through radical-based synthetic methodologies. Cholesteryl linoleate and
      arachidonate esters are interesting targets for their biochemical connection with
      membrane phospholipid turnover and their well-known roles in cardiovascular
      health. The synthesis of monotrans isomers of PUFA cholesteryl esters was
      achieved by a thiyl radical-catalyzed cis-trans isomerization. Valuable NMR, IR,
      and Raman spectroscopic data have been collected for promising application in
      metabolomics and lipidomics. The identification of monotrans cholesteryl ester
      isomers was carried out in human plasma by GC, Raman, and IR analyses,
      demonstrating for the first time the presence of specific regiosiomers connected
      to free radical stress. This work helps to highlight the chemical biology
      approach for the access to molecular libraries applicable to biomarker
      development, and the cis-trans isomerization as a relevant process to be
      integrated in the puzzling scenario of free radical-mediated lipid modifications.

PMID- 21851065
TI  - Chemical and spatial differentiation of syringyl and guaiacyl lignins in poplar
      wood via time-of-flight secondary ion mass spectrometry.
AB  - As a major component in plant cell walls, lignin is an important factor in
      numerous industrial processes, especially in wood saccharification and
      fermentation to biofuels. The ability to chemically differentiate and spatially
      locate lignins in wood cell structures provides an important contribution to the
      effort to improve these processes. The spatial distribution of the syringyl (S)
      and guaiacyl (G) lignins, both over larger regions and within a single cell wall,
      on poplar ( Populus trichocarpa ) wood cross-sections was determined via time-of
      flight secondary ion mass spectrometry (ToF-SIMS). This is the first time that
      direct chemically specific mass spectrometric mapping has been employed to
      elucidate the spatial distribution of S and G lignins. In agreement with results
      obtained by UV microscopy, ToF-SIMS images clearly show that the guaiacyl lignin
      is predominantly located in the vessel cell walls of poplar wood while syringyl
      lignin is mainly located in the fiber cell walls. The G/S ratio in vessel cell
      walls was determined to be approximately twice that found in fiber cell walls. A
      combination of Bi ToF-SIMS spectral image acquisition and C(60) sputtering
      provided the ability to attain the combination of spatial resolution and signal
      to-noise necessary to determine the distribution of S and G lignins in a single
      cell wall. By this technique, it was possible to demonstrate that more guaiacyl
      lignin is located in the middle lamella layer and more syringyl lignin is located
      in the inner cell wall area.

PMID- 21851064
TI  - Virtual screening targeting the urokinase receptor, biochemical and cell-based
      studies, synthesis, pharmacokinetic characterization, and effect on breast tumor
      metastasis.
AB  - Virtual screening targeting the urokinase receptor (uPAR) led to (+/-)-3
      (benzo[d][1,3]dioxol-5-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-phenylbutan-1
      amine 1 (IPR-1) and N-(3,5-dimethylphenyl)-1-(4-isopropylphenyl)-5-(piperidin-4
      yl)-1H-pyrazole-4-carboxamide 3 (IPR-69). Synthesis of an analogue of 1, namely,
      2 (IPR-9), and 3 led to breast MDA-MB-231 invasion, migration and adhesion assays
      with IC(50) near 30 MUM. Both compounds blocked angiogenesis with IC(50) of 3
      MUM. Compounds 2 and 3 inhibited cell growth with IC(50) of 6 and 18 MUM and
      induced apoptosis. Biochemical assays revealed leadlike properties for 3, but not
      2. Compound 3 administered orally reached peak concentration of nearly 40 MUM
      with a half-life of about 2 h. In NOD-SCID mice inoculated with breast TMD-231
      cells in their mammary fat pads, compound 3 showed a 20% reduction in tumor
      volumes and less extensive metastasis was observed for the treated mice. The
      suitable pharmacokinetic properties of 3 and the encouraging preliminary results
      in metastasis make it an ideal starting point for next generation compounds.

PMID- 21851066
TI  - Polymer brush controlled bioinspired calcium phosphate mineralization and bone
      cell growth.
AB  - Polymer brushes on thiol-modified gold surfaces were synthesized by using
      terminal thiol groups for the surface-initiated free radical polymerization of
      methacrylic acid and dimethylaminoethyl methacrylate, respectively. Atomic force
      microscopy shows that the resulting poly(methacrylic acid) (PMAA) and
      poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes are homogeneous. Contact
      angle measurements show that the brushes are pH-responsive and can reversibly be
      protonated and deprotonated. Mineralization of the brushes with calcium phosphate
      at different pH yields homogeneously mineralized surfaces, and preosteoblastic
      cells proliferate on both the nonmineralized and mineralized surfaces. The number
      of living cells on the mineralized hybrid surfaces is ca. 3 times (PDMAEMA) and
      10 times (PMAA) higher than on the corresponding nonmineralized brushes.

PMID- 21851067
TI  - Development of novel efficient SIN vectors with improved safety features for
      Wiskott-Aldrich syndrome stem cell based gene therapy.
AB  - Gene therapy is a promising therapeutic approach to treat primary
      immunodeficiencies. Indeed, the clinical trial for the Wiskott-Aldrich Syndrome
      (WAS) that is currently ongoing at the Hannover Medical School (Germany) has
      recently reported the correction of all affected cell lineages of the
      hematopoietic system in the first treated patients. However, an extensive study
      of the clonal inventory of those patients reveals that LMO2, CCND2 and MDS1/EVI1
      were preferentially prevalent. Moreover, a first leukemia case was observed in
      this study, thus reinforcing the need of developing safer vectors for gene
      transfer into HSC in general. Here we present a novel self-inactivating (SIN)
      vector for the gene therapy of WAS that combines improved safety features. We
      used the elongation factor 1 alpha (EFS) promoter, which has been extensively
      evaluated in terms of safety profile, to drive a codon-optimized human WASP cDNA.
      To test vector performance in a more clinically relevant setting, we transduced
      murine HSPC as well as human CD34+ cells and also analyzed vector efficacy in
      their differentiated myeloid progeny. Our results show that our novel vector
      generates comparable WAS protein levels and is as effective as the clinically
      used LTR-driven vector. Therefore, the described SIN vectors appear to be good
      candidates for potential use in a safer new gene therapy protocol for WAS, with
      decreased risk of insertional mutagenesis.

PMID- 21851068
TI  - Probing the nature of the Co(III) ion in corrins: a comparison of the
      thermodynamics and kinetics of the ligand substitution reactions of
      aquacyanocobyrinic acid heptamethyl ester and stable yellow aquacyanocobyrinic
      acid heptamethyl ester.
AB  - Equilibrium constants (log K) for the substitution of coordinated H(2)O in
      aquacyanocobyrinic acid heptamethyl ester (aquacyanocobester, ACCbs) and stable
      yellow aquacyanocobyrinic acid heptamethyl ester (stable yellow
      aquacyanocobester, ACSYCbs), in which oxidation of the C5 carbon of the corrin
      interrupts the normal delocalized system of corrins, by ligands with soft (CN(-),
      SO(3)(2-), and S(2)O(3)(2-)) and hard (NO(2)(-) and N(3)(-)) donors have been
      determined. The ligands with a harder donor atom (N in N(3)(-) and NO(2)(-))
      produce DeltaH values that are more negative in their reactions with ACSYCbs than
      with ACCbs. If the donor atom is softer (C in CN(-) and S in SO(3)(2-)), then
      DeltaH is less positive, or more negative, for reactions with ACCbs than with
      ACSYCbs. The softer metal in ACCbs has a preference for softer ligands and the
      harder metal in ACSYCbs for the harder ligands. A kinetics study in which CN(-)
      substitutes H(2)O on Co(III) shows that ACCbs is more labile than ACSYCbs; the
      second-order rate constant k(II) is between 4.6 (at 5  degrees C) and 2.6 (at 35 
      degrees C) times larger. DeltaH(?) for the reaction of CN(-) with ACCbs is
      smaller by some 12 kJ mol(-1) than that for the reaction with ACSYCbs, consistent
      with an earlier transition state in which bonding between the softer metal of
      ACCbs and the ligand is greater than that of ACSYCbs with its harder metal. This
      difference in DeltaH(?) makes ACCbs over 100 times more labile, although the
      effect is masked by a DeltaS(?) value that is over 30 J K(-1) mol(-1) more
      negative. There is a significant increase in the inertness of Co(III) upon a
      decrease in the extent of conjugation of the corrin ligand. Modifying the
      electronic structure of the equatorial ligand in the cobalt corrins can modify
      the thermodynamics and kinetics of its reactions with exogenous ligands.

PMID- 21851069
TI  - Probing the nature of the Co(III) ion in corrins: the structural and electronic
      properties of dicyano- and aquacyanocobyrinic acid heptamethyl ester and a stable
      yellow dicyano- and aquacyanocobyrinic acid heptamethyl ester.
AB  - A stable yellow derivative of cobyrinic acid heptamethyl ester, (5R,6R)
      Coalpha,Cobeta-dicyano-5,6-dihydro-5-hydroxy-heptamethylcob(III)yrinate-c,6
      lactone (DCSYCbs), was prepared from dicyanocobyrinic acid heptamethyl ester
      (DCCbs). The C5 carbon is oxidized and the c side chain cyclized to form a
      lactone at C6; the 13 atom, 14 pi-e(-) delocalized system of corrins is
      interrupted, giving a triazamethine system with four conjugated double bonds
      between N22 and N24 and an isolated double bond between N21 and C4. Stable yellow
      aquacyanocobyrinic acid heptamethyl ester (ACSYCbs) was prepared by driving off
      HCN with N(2) in a methanol/acetic acid solution. The electronic spectra of DCCbs
      and DCSYCbs appear similar except that the bands in DCSYCbs are shifted to
      shorter wavelengths and the gamma-band is much less intense. The experimental
      spectra were adequately modeled using TD-DFT at the PBE1PBE/6-311G(d,p) level of
      theory. DCSYCbs crystallizes in the space group P2(1)2(1)2(1) (R(1) = 6.08%) with
      Z = 4, including one methanol solvent molecule and one water molecule per
      cobester. The addition of a hydroxyl group at C5 causes loss of the double bond
      between C5 and C6 and elongation of the C5-C6 bond. From a combination of two
      dimensional (1)H TOCSY and ROESY NMR spectra and (1)H/(13)C HSQC and HMBC data,
      the complete (1)H and (13)C NMR assignments of DCSYCbs were possible, except for
      two of the ester methyl groups and the (13)C resonances of the two axial cyanide
      ligands. The latter were assigned using relative chemical shifts calculated by
      GIAO-DFT methods. The (59)Co resonance of DCCbs was observed at 4074 ppm while
      that of DCSYCbs is shifted downfield to 4298 ppm. Comparison with available
      (59)Co data of analogous systems suggests that the more pi-conjugated corrin of
      DCCbs interacts more strongly with the metal than the less extensively conjugated
      macrocycle of DCSYCbs. As the strength of the interaction between Co(III) and an
      equatorial macrocycle increases, nu(CN) of axially coordinated CN(-) shifts to
      lower frequency; in DCSYCbs and DCCbs nu(CN) occurs at 2138 and 2123 cm(-1),
      respectively. Hence the corrin ligand in DCCbs interacts more strongly with the
      metal than the stable yellow corrin ligand, with its diminished conjugation. The
      UV-vis spectral data and DFT-calculated MOs are consistent with greater overlap
      between the corrin and the metal orbitals in DCCbs relative to DCSYCbs, which
      gives the metal in the former a softer, more covalent character.

PMID- 21851070
TI  - Stereoselectivities and regioselectivities of (4 + 3) cycloadditions between
      allenamide-derived chiral oxazolidinone-stabilized oxyallyls and furans:
      experiment and theory.
AB  - A systematic investigation of the regioselectivities and stereoselectivities of
      (4 + 3) cycloadditions between unsymmetrical furans and a chiral oxazolidinone
      substituted oxyallyl is presented. Cycloadditions were performed using an
      oxyallyl containing a (R)-4-phenyl-2-oxazolidinone auxiliary (2(Ph)), under
      either thermal or ZnCl(2)-catalyzed conditions. Reactions of 2(Ph) with 2
      substituted furans gave syn cycloadducts selectively, while cycloadditions with 3
      substituted furans gave selectively anti cycloadducts. The stereoselectivities
      were in favor of a single diastereoisomer (I) in all but one case (2-CO(2)R).
      Density functional theory calculations were performed to explain the
      selectivities. The results support a mechanism in which all cycloadducts are
      formed from the E isomer of the oxyallyl (in which the oxazolidinone C?O and
      oxyallyl oxygen are anti to each other) or the corresponding (E)-ZnCl(2) complex.
      The major diastereomer is derived from addition of the furan to the more crowded
      face of the oxyallyl. Crowded transition states are favored because they possess
      a stabilizing CH-pi interaction between the furan and the Ph group.

PMID- 21851071
TI  - Simulated annealing and density functional theory calculations of structural and
      energetic properties of the ammonium chloride clusters (NH4Cl)n, (NH4+)(NH4Cl)n,
      and (Cl-)(NH4Cl)n, n = 1-13.
AB  - Simulated annealing Monte Carlo conformer searches using the "mag-walking"
      algorithm are employed to locate the global minima of molecular clusters of
      ammonium chloride of the types (NH(4)Cl)(n), (NH(4)(+))(NH(4)Cl)(n), and (Cl(
      ))(NH(4)Cl)(n) with n = 1-13. The M06-2X density functional theory method is used
      to refine and predict the structures, energies, and thermodynamic properties of
      the neutral, cation, and anion clusters. For selected small clusters, the
      resulting structures are compared to those obtained from a variety of models and
      basis sets, including RI-MP2 and B3LYP calculations. M06-2X calculations predict
      enhanced stability of the (NH(4)(+))(NH(4)Cl)(n) clusters when n = 3, 6, 8, and
      13. This prediction corresponds favorably to anomalies previously observed in
      thermospray mass spectroscopy experiments. The (NH(4)Cl)(n) clusters show
      alternations in stability between even and odd values of n. Clusters of the type
      (Cl(-))(NH(4)Cl)(n) display a magic number distribution different from that of
      the cation clusters, with enhanced stability predicted for n = 2, 6, and 11. None
      of the observed cluster structures resemble the room-temperature CsCl structure
      of NH(4)Cl(s), which is consistent with previous work. Numerous clusters have
      structures reminiscent of the higher-temperature, rock-salt phase of the solid
      ammonium halides.

PMID- 21851072
TI  - Transplanted induced pluripotent stem cells improve cardiac function and induce
      neovascularization in the infarcted hearts of db/db mice.
AB  - Recently, we proclaimed that induced pluripotent stem (iPS) cells generated from
      H9c2 cells, following transplantation into infarcted nondiabetic mice, can
      inhibit apoptosis and differentiate into cardiac myocytes. iPS cells can be an
      ideal candidate to expand regenerative medicine to the clinic. Therefore,
      examining the wide range of their potential to differentiate into neovascular
      cell types remains a major interest. We hypothesized that transplanted iPS cells
      in the infarcted diabetic db/db and nondiabetic mice can differentiate into
      vascular smooth muscle (VSM) and endothelial cells (ECs) as well as activate
      endogenous c-kit progenitor cells to enhance neovascularization along with
      improved cardiac function. We transplanted intramyocardially 50,000 iPS cells in
      the peri-infarct zone of infarcted db/db and C57BL/6 mice and hearts were
      examined at D14 post-MI. Cardiac function was examined using echocardiography.
      Our data implies that there was a significant (p < 0.001) increase in VSM and ECs
      in the infarcted heart following iPS cell transplantation compared with MI and
      sham groups in both db/db and C57BL/6 animals. Furthermore, the MI+iPS cell
      transplanted group also displayed a significant (p < 0.001) increase in c
      kit(+ve) activated VSM and ECs confirmed with combined stainings of c-kit and
      cell specific markers, compared with respective controls. Next, our histology
      data in the MI+iPS cell group also establishes a significant (p < 0.05) increase
      in coronary artery vessels compared with MI, suggesting neovascularization.
      Furthermore, our data demonstrates significant improved cardiac function
      following iPS cell transplantation compared with MI. Overall increased
      neovascularization in the infarcted db/db and C57BL/6 mice is associated with
      improved cardiac function following iPS cell transplantation.

PMID- 21851073
TI  - Considerations on orthogonality duality in comprehensive two-dimensional gas
      chromatography.
AB  - The term "orthogonal" in comprehensive two-dimensional gas chromatography (GC *
      GC) has a double sided meaning as it stands for a separation resulting from the
      combination of two independent retention mechanisms (Giddings, J. C. J. High
      Resolut. Chromatogr. 1987, 10, 319) but also for a 2D separation where the
      components are evenly distributed over the entire 2D space. It is shown in the
      present study that a nonorthogonal GC * GC system associating a polar stationary
      phase in the first dimension (poly(ethylene glycol)) to a nonpolar one in the
      second dimension (poly(dimethyl siloxane)) leads to a structured chromatogram, a
      high peak capacity, and a great 2D space occupation. This idea is demonstrated
      through the characterization of oxygenated compounds in a coal-derived middle
      distillate. Results show a clear separation between oxygenated species and
      hydrocarbons which are classified into linear alkanes, cyclic alkanes, and
      aromatics. A breakthrough configuration combining a polar poly(ethylene glycol)
      first dimension and a trifluoropropyl methyl stationary phase in the second
      dimension enabled a unique identification and quantification of linear, cyclic,
      and aromatic alcohols. This configuration which could be considered as
      nonorthogonal still involves two different retention mechanisms: polarity and
      boiling point in the first dimension and electronic interactions in the second
      dimension. It is selective toward electronegative poles of alcohols and phenols.
      The contributions of these two configurations compared to a conventional
      orthogonal system as well as their roles for oxygenated compounds speciation are
      highlighted. This contribution is measured through three 2D space occupation
      factors. It appears through these two examples that orthogonality is intimately
      linked to analyte properties, and a general concept of dimensionality must be
      considered.

PMID- 21851074
TI  - Nano-TiO2 enhanced photofermentative hydrogen produced from the dark fermentation
      liquid of waste activated sludge.
AB  - After anaerobic dark fermentation of waste activated sludge (WAS) for hydrogen
      production, there are a large number of organic compounds including protein,
      polysaccharide, and volatile fatty acids left in the dark fermentation liquid,
      which can be further bioconverted to hydrogen by photofermentation techniquea. In
      this study, the enhancement of photofermentative hydrogen produced from WAS dark
      fermentation liquid by using nano-TiO2 is reported. First, high concentration of
      NH(4)(+)-N in the dark fermentation liquid was observed to inhibit the
      photofermentative hydrogen production, and its removal was essential. Then the
      effect of nano-TiO2 on photofermentative hydrogen generation was investigated,
      and the addition of 100 mg/L nano-TiO2 increased hydrogen by 46.1%. Finally, the
      mechanisms for nano-TiO2 improving hydrogen production were investigated. It was
      found that nano-TiO2 improved the decomposition of protein and polysaccharide to
      small-molecule organic compounds and promoted the growth of photosynthetic
      bacteria and the activity of nitrogenase but decreased the H2-uptake hydrogenase
      activity.

PMID- 21851076
TI  - Circularly polarized luminescence as a probe for long-range interactions in
      molecular aggregates.
AB  - The extreme sensitivity of circularly polarized luminescence (CPL) to long-range
      excitonic interactions inside a helical aggregate is investigated. It is found to
      persist even in the presence of strong energetic disorder and coupling of the
      exciton to molecular vibrations, when the emitting exciton is localized to only a
      few chromophores. The CPL dissymmetry, g(lum), is found to depend on a modulated
      sum over the excitonic couplings, ?(n,s)J(n,n+s)s sin(phis), where J(n,n+s) is
      the coupling between molecules separated by s lattice spacings and phi is the
      pitch angle between adjacent chromophores. The validity of this relation is
      confirmed through full-scale numerical simulations of helical MPOV4 aggregates
      using the disordered Holstein Hamiltonian. In addition, an analytical expression
      for g(lum) is obtained for a helical chain containing a single, energetically
      detuned chromophore to represent strong disorder. Subsequently, the resulting
      expression is generalized to include full distributed disorder. Our results
      demonstrate that the spatial dependence of extended interactions can be extracted
      from experimental spectra, without having details on disorder or exciton
      vibrational coupling.

PMID- 21851077
TI  - A blue corrinoid from partial degradation of vitamin B12 in aqueous bicarbonate:
      spectra, structure, and interaction with proteins of B12 transport.
AB  - Cobalamin (Cbl) is a complex cofactor produced only by bacteria but used by all
      animals and humans. Cyanocobalamin (vitamin B(12), CNCbl) is one commonly
      isolated form of cobalamin. B(12) belongs to a large group of corrinoids, which
      are characterized by a distinct red color conferred by the system of conjugated
      double bonds of the corrin ring retaining a Co(III) ion. A unique blue Cbl
      derivative was produced by hydrolysis of CNCbl in a weakly alkaline aqueous
      solution of bicarbonate. This corrinoid was purified and isolated as dark blue
      crystals. Its spectroscopic analysis and X-ray crystallography revealed B-ring
      opening with formation of 7,8-seco-cyanocobalamin (7,8-sCNCbl). The unprecedented
      structural change was caused by cleavage of the peripheral C-C bond between
      saturated carbons 7 and 8 of the corrin macrocycle accompanied by formation of a
      C?C bond at C7 and a carbonyl group at C8. Additionally, the C-amide was
      hydrolyzed to a carboxylic acid. The extended conjugation of the pi-system caused
      a considerable red shift of the absorbance spectrum. Formation and degradation of
      7,8-sCNCbl were analyzed qualitatively. Its interaction with the proteins of
      mammalian Cbl transport revealed both a slow binding kinetics and a low overall
      affinity. The binding data were compared to those of other monocarboxylic
      derivatives and agreed with the earlier proposed scheme for two-step ligand
      recognition. The obtained results are consistent with the structural models of
      7,8-sCNCbl and the transport proteins intrinsic factor and transcobalamin.
      Potential applications of the novel derivative for drug conjugation are
      discussed.

PMID- 21851078
TI  - Liquid-liquid coexistence in NaCl aqueous solutions: a simulation study of
      concentration effects.
AB  - In this paper we investigate by means of molecular dynamics computer simulations
      how the hypothesized liquid-liquid critical point of water shifts in supercooled
      aqueous solutions of salt as a function of concentration. We study sodium
      chloride solutions in TIP4P water, NaCl(aq), for concentrations c = 1.36 mol/kg
      and c = 2.10 mol/kg. The liquid-liquid critical point is found up to the highest
      concentration investigated, and its position in the P-T plane shifts to higher
      temperatures and lower pressures upon increasing concentration. For c = 2.10
      mol/kg it is also located very close to the temperature of maximum density line
      of the system. The results are discussed and compared with previous results for
      bulk TIP4P water and for c = 0.67 mol/kg NaCl(aq) and with experimental findings.
      We observe a progressive shrinkage of the low-density liquid region when the
      concentration of salt increases; this suggests an eventual disappearance of the
      liquid-liquid coexistence upon further increase of NaCl concentration.

PMID- 21851079
TI  - Probing the reactivity and electronic structure of a uranium(V) terminal oxo
      complex.
AB  - Treatment of the U(III)-ylide adduct U(CH(2)PPh(3))(NR(2))(3) (1, R = SiMe(3))
      with TEMPO generates the U(V) oxo metallacycle
      [Ph(3)PCH(3)][U(O)(CH(2)SiMe(2)NSiMe(3))(NR(2))(2)] (2) via O-atom transfer, in
      good yield. Oxidation of 2 with 0.85 equiv of AgOTf affords the neutral U(VI)
      species U(O)(CH(2)SiMe(2)NSiMe(3))(NR(2))(2) (3). The electronic structures of 2
      and 3 are investigated by DFT analysis. Additionally, the nucleophilicity of the
      oxo ligands in 2 and 3 toward Me(3)SiI is explored.

PMID- 21851080
TI  - Palladium-catalyzed direct arylation of heteroaromatic compounds: improved
      conditions utilizing controlled microwave heating.
AB  - A versatile and rapid microwave-assisted procedure for the palladium-catalyzed
      direct arylation of heterocycles by aryl bromides and heteroaryl bromides is
      described. This novel protocol features short coupling times (10-60 min) and low
      catalyst loadings (1 mol %) and allows the successful arylation of previously
      unreactive heterocyclic substrates.

PMID- 21851081
TI  - Compound-specific chlorine isotope analysis: a comparison of gas
      chromatography/isotope ratio mass spectrometry and gas chromatography/quadrupole
      mass spectrometry methods in an interlaboratory study.
AB  - Chlorine isotope analysis of chlorinated hydrocarbons like trichloroethylene
      (TCE) is of emerging demand because these species are important environmental
      pollutants. Continuous flow analysis of noncombusted TCE molecules, either by gas
      chromatography/isotope ratio mass spectrometry (GC/IRMS) or by GC/quadrupole mass
      spectrometry (GC/qMS), was recently brought forward as innovative analytical
      solution. Despite early implementations, a benchmark for routine applications has
      been missing. This study systematically compared the performance of GC/qMS versus
      GC/IRMS in six laboratories involving eight different instruments (GC/IRMS,
      Isoprime and Thermo MAT-253; GC/qMS, Agilent 5973N, two Agilent 5975C, two Thermo
      DSQII, and one Thermo DSQI). Calibrations of (37)Cl/(35)Cl instrument data
      against the international SMOC scale (Standard Mean Ocean Chloride) deviated
      between instruments and over time. Therefore, at least two calibration standards
      are required to obtain true differences between samples. Amount dependency of
      delta(37)Cl was pronounced for some instruments, but could be eliminated by
      corrections, or by adjusting amplitudes of standards and samples. Precision
      decreased in the order GC/IRMS (1sigma ~ 0.10/00), to GC/qMS (1sigma ~ 0.2
      0.50/00 for Agilent GC/qMS and 1sigma ~ 0.2-0.90/00 for Thermo GC/qMS).
      Nonetheless, delta(37)Cl values between laboratories showed good agreement when
      the same external standards were used. These results lend confidence to the
      methods and may serve as a benchmark for future applications.

PMID- 21851082
TI  - Pathway-dependent isotope fractionation during aerobic and anaerobic degradation
      of monochlorobenzene and 1,2,4-trichlorobenzene.
AB  - Stable carbon isotope fractionation is a valuable tool for monitoring natural
      attenuation and to establish the fate of groundwater contaminants. In this study,
      we measured carbon isotope fractionation during aerobic and anaerobic degradation
      of two chlorinated benzenes: monochlorobenzene (MCB) and 1,2,4-trichlorobenzene
      (1,2,4-TCB). MCB isotope fractionation was measured in anaerobic methanogenic
      microcosms, while 1,2,4-TCB isotope experiments were carried out in both aerobic
      and anaerobic microcosms. Large isotope fractionation was observed in both the
      anaerobic microcosm experiments. Enrichment factors (epsilon) for anaerobic
      reductive dechlorination of MCB and 1,2,4-TCB were -5.00/00 +/- 0.20/00 and 
      3.00/00 +/- 0.40/00, respectively. In contrast, no significant isotope
      fractionation was found during aerobic microbial degradation of 1,2,4-TCB. The
      cleavage of a C-Cl sigma bond occurs during anaerobic reductive dechlorination of
      MCB and 1,2,4-TCB, while no sigma bond cleavage is involved during aerobic
      degradation via dioxygenase. The difference in isotope fractionation for aerobic
      versus anaerobic biodegradation of MCB and 1,2,4-TCB can be explained by the
      difference in the initial step of aerobic versus anaerobic biodegradation
      pathways.

PMID- 21851083
TI  - Design and synthesis of resveratrol-based nitrovinylstilbenes as antimitotic
      agents.
AB  - A new series of resveratrol analogues was designed, synthesized, and demonstrated
      to be tubulin polymerization inhibitors. Most of these compounds exhibited
      antiproliferative activity and inhibited in vitro tubulin polymerization
      effectively at concentrations of 4.4-68.1 and 17-62 MUM, respectively. Flow
      cytometry studies showed that compounds 7c, 7e, and 7g arrested cells in the G2/M
      phase of the cell cycle. Immunocytochemistry revealed loss of intact microtubule
      structure in cells treated with 7c and 7e. Docking of compounds 7c and 7e with
      tubulin suggested that the A-ring of the compounds occupies the colchicine
      binding site of tubulin, which coordinates with Cys241, Leu242, Ala250, Val318,
      Val328, and I378, and that the nitrovinyl side chain forms two hydrogen bonds
      with the main loop of the beta-chain at Asn249 and Ala250.

PMID- 21851084
TI  - Asymmetric syntheses of alpha-methyl gamma-amino acid derivatives.
AB  - This project was undertaken to demonstrate the potential of asymmetric
      hydrogenations mediated by the chiral, carbene-oxazoline analogue of Crabtree's
      catalyst "cat" in asymmetric hydrogenations of allylic amine derivatives of amino
      acids. Peripheral features of the substrates (protecting groups, functional
      groups related by redox processes, and alkene geometries) were varied to optimize
      the stereochemical vectors exerted by the substrate and align them with the
      catalyst vector. N-Acetyl-protected, O-TBDPS-protected allylic substrates 9a-e
      emerged as the best for this reaction; syn-products were formed from the E
      alkenes, while the Z-isomers gave anti-target materials, both with high
      diastereoselectivities. This study featured asymmetric catalysis to elaborate
      optically active substrates into more stereochemically complex chirons; we
      suggest that the approach used, optimization of stereocontrol by varying
      peripheral aspects of the substrate, tends to be easier than de novo catalyst
      design for each substrate type. In other words, optimization of the substrate
      vector is likely to be more facile than enhancement of the catalyst vector via
      ligand modifications.

PMID- 21851085
TI  - Probing two-photon properties of molecules: large non-Condon effects dominate the
      resonance hyper-Raman scattering of rhodamine 6G.
AB  - Experimentally measured resonance hyper-Raman (RHR) spectra spanning the S(1) <-
      S(0), S(2) <- S(0), and S(3) <- S(0) transitions in rhodamine 6G (R6G) have been
      recorded. These spectra are compared to the results of first-principles
      calculations of the RHR intensity that include both Franck-Condon (A-term) and
      non-Condon (B-term) scattering effects. Good agreement between the experimental
      and theoretical results is observed, demonstrating that first-principles
      calculations of hyper-Raman intensities are now possible for large molecules such
      as R6G. Such agreement indicates that RHR spectroscopy will now be a routine aid
      for probing multiphoton processes. This work further shows that optimization of
      molecular properties to enhance either A- or B-term scattering might yield
      molecules with significantly enhanced two-photon properties.

PMID- 21851086
TI  - Hydrophobic surface induced activation of Pseudomonas cepacia lipase immobilized
      into mesoporous silica.
AB  - Lipase from Pseudomonas cepacia (PCL) was successfully immobilized into siliceous
      mesocellular foams (MCFs) with various hydrophobic/hydrophilic surfaces. The
      catalytic performances of immobilized PCL were investigated using the
      transesterification reaction and hydrolytic reaction as model reactions. The
      specific activity of immobilized PCL greatly increased with enhanced surface
      hydrophobicity of MCFs, mainly because of lipase activation via hydrophobic
      interaction between alkyl groups in MCFs and the surface loop (so-called "lid")
      of PCL. Conformational changes of immobilized PCL were further investigated using
      time-resolved fluorescence spectroscopy with Trp as an intrinsic probe. When the
      immobilized PCL was suspended in phosphate buffer, short-lived tau(1) shortened
      and the fractional contribution of tau(1) significantly increased with the
      increasing level of surface hydrophobicity of MCFs. These results revealed that
      Trp(s) of the immobilized PCL were surrounded by a hydrophilic microenvironment
      because of the fact that the opened "lid" permitted the diffusion of water to the
      active site cleft. However, for the immobilized PCL suspended in n-hexane, long
      lived tau(3) increased with the increase of surface hydrophobicity of MCFs. The
      reduced interaction between Trp(s) and the surrounding protein matrix was due to
      intercalation of n-hexane into the active site cleft when the lipase was in open
      conformation. The above results demonstrated that PCL immobilized into MCF with
      hydrophobic surfaces were in an activated open conformation.

PMID- 21851088
TI  - Molecular gallosilicates and their group 4 multimetallic derivatives.
AB  - Reaction between the silanediol (HO)(2)Si(OtBu)(2) and gallium amides,
      LGaCl(NHtBu) and LGa(NHEt)(2) (L = [HC{C(Me)N(Ar)}(2)](-), Ar = 2,6
      iPr(2)C(6)H(3)), respectively, resulted in the facile isolation of molecular
      gallosilicates LGaCl(MU-O)Si(OH)(OtBu)(2) (1) and LGa(NHEt)(MU-O)Si(OH)(OtBu)(2)
      (2). Compound 2 easily reacts with 1 equiv of water to form the unique
      gallosilicate-hydroxide LGa(OH.THF)(MU-O)Si(OH)(OtBu)(2) (3). Compounds 1-3
      contain the simple Ga-O-SiO(3) framework and are the first structurally
      authenticated molecular gallosilicates. These compounds may be used not only as
      models for gallosilicate-based materials but also as further reagents because of
      the presence of reactive functional groups attached to both gallium and silicon
      atoms. Accordingly, seven molecular heterometallic compounds were obtained from
      the reactions between compound 3 and group 4 amides M(NMe(2))(4) (M = Ti, Zr) or
      M(NEt(2))(4) (M = Ti, Zr, Hf). Hence, by tuning the reactions conditions and
      stoichiometries, it was possible to isolate and structurally characterize the
      complete 1:1 and 2:1 series (4-10). Completely inorganic cores of types M-O-Ga-O
      Si-O and spiro M[O-Ga-O-Si-O](2) were obtained and characterized by common
      spectroscopic techniques.

PMID- 21851087
TI  - Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione
      reductase inhibitors: discovery, synthesis, and characterization of their binding
      mode by protein crystallography.
AB  - Trypanothione reductase (TryR) is a genetically validated drug target in the
      parasite  Trypanosoma brucei , the causative agent of human African
      trypanosomiasis. Here we report the discovery, synthesis, and development of a
      novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In
      addition, a high resolution crystal structure of TryR, alone and in complex with
      substrates and inhibitors from this series, is presented. This represents the
      first report of a high resolution complex between a noncovalent ligand and this
      enzyme. Structural studies revealed that upon ligand binding the enzyme undergoes
      a conformational change to create a new subpocket which is occupied by an aryl
      group on the ligand. Therefore, the inhibitor, in effect, creates its own small
      binding pocket within the otherwise large, solvent exposed active site. The TryR
      ligand structure was subsequently used to guide the synthesis of inhibitors,
      including analogues that challenged the induced subpocket. This resulted in the
      development of inhibitors with improved potency against both TryR and T. brucei
      parasites in a whole cell assay.

PMID- 21851089
TI  - Synthesis of a new [6]-gingerol analogue and its protective effect with respect
      to the development of metabolic syndrome in mice fed a high-fat diet.
AB  - To determine the effects of a [6]-gingerol analogue (6G), a major chemical
      component of the ginger rhizome, and its stable analogue after digestion in
      simulated gastric fluid, aza-[6]-gingerol (A6G), on diet-induced body fat
      accumulation, we synthesized 6G and A6G. Mice were fed either a control regular
      rodent chow, a high-fat diet (HFD), or a HFD supplemented with 6G and A6G.
      Magnetic resonance imaging adiposity parameters of the 6G- and A6G-treated mice
      were compared with those of control mice. Supplementation with 6G and A6G
      significantly reduced body weight gain, fat accumulation, and circulating levels
      of insulin and leptin. The mRNA levels of sterol regulatory element-binding
      protein 1c (SREBP-1c) and acetyl-CoA carboxylase 1 in the liver were
      significantly lower in mice fed A6G than in HFD control mice. Our findings
      indicate that A6G, rather than 6G, enhances energy metabolism and reduces the
      extent of lipogenesis by downregulating SREBP-1c and its related molecules, which
      leads to the suppression of body fat accumulation.

PMID- 21851090
TI  - A protein arginine N-methyltransferase 1 (PRMT1) and 2 heteromeric interaction
      increases PRMT1 enzymatic activity.
AB  - Protein arginine N-methyltransferases (PRMTs) act in signaling pathways and gene
      expression by methylating arginine residues within target proteins. PRMT1 is
      responsible for most cellular arginine methylation activity and can work
      independently or in collaboration with other PRMTs. In this study, we demonstrate
      a direct interaction between PRMT1 and PRMT2 using co-immunoprecipitation,
      bimolecular fluorescence complementation, and enzymatic assays. As a result of
      this interaction, PRMT2 stimulated PRMT1 activity, affecting its apparent V(max)
      and K(M) values in vitro and increasing the production of methylarginines in
      cells. Active site mutations and regional deletions from PRMT1 and -2 were also
      investigated, which demonstrated that complex formation required full-length,
      active PRMT1. Although the inhibition of methylation by adenosine dialdehyde
      prevented the interaction between PRMT1 and -2, it did not prevent the
      interaction between PRMT1 and a truncation mutant of PRMT2 lacking its Src
      homology 3 (SH3) domain. This result suggests that the SH3 domain may mediate an
      interaction between PRMT1 and -2 in a methylation-dependent fashion. On the basis
      of our findings, we propose that PRMT1 serves as the major methyltransferase in
      cells by forming higher-order oligomers with itself, PRMT2, and possibly other
      PRMTs.

PMID- 21851091
TI  - Combed single DNA molecules imaged by secondary ion mass spectrometry.
AB  - Studies of replication, recombination, and rearrangements at the level of
      individual molecules of DNA are often limited by problems of resolution or of
      perturbations caused by the modifications that are needed for imaging. The
      Combing-Imaging by Secondary Ion Mass Spectrometry (SIMS) (CIS) method helps
      solve these problems by combining DNA combing, cesium flooding, and quantitative
      imaging via the NanoSIMS 50. We show here that CIS can reveal, on the 50 nm
      scale, individual DNA fibers labeled with different, nonradioactive isotopes and,
      moreover, that it can quantify these isotopes so as to detect and measure the
      length of one or more short nucleic acid fragments associated with a longer
      fiber.

PMID- 21851092
TI  - The O-H stretching mode of a prototypical photoacid as a local dielectric probe.
AB  - We investigate the OH stretch vibrational frequency shifts of a prototype
      photoacid, 2-naphthol (2N), when dissolved in solvents of low polarity. We
      combine femtosecond mid-infrared spectroscopy and a theoretical model based on
      the Pullin-van der Zwan-Hynes perturbative approach to explore vibrational
      solvatochromic effects in the ground S(0) and the first electronically excited
      (1)L(b) states. The model is parametrized using density functional theory (DFT),
      at the B3LYP/TZVP and TD-B3LYP/TZVP levels for the 2N chromophore in the S(0) and
      (1)L(b) states, respectively. From the agreement between experiment and theory we
      conclude that vibrational solvatochromic effects are dominated by the
      instantaneous dielectric response of the solvent, while time-dependent nuclear
      rearrangements are of secondary importance.

PMID- 21851093
TI  - Sulfur dioxide emissions from combustion in china: from 1990 to 2007.
AB  - China has become the world's largest emitter of SO(2) since 2005, and aggressive
      deployment of flue gas desulfurization (FGD) at coal-fired power plants appeared
      in China when facing the formidable pressure of environment pollution. In this
      work, we estimate the annual emission from combustion sources at provincial
      levels in China from 1990 to 2007, with updated data investigations. We have
      implemented the method of transportation matrix to gain a better understanding of
      sulfur content of coal in consuming provinces, which in turn improved the
      inventory. The total emissions from combustion in 2007 were 28.3 Tg, half of
      which was contributed by coal-fired power plants. Meanwhile, the industrial
      boiler coal combustion and residential coal consumed in centralized heating were
      responsible for another 32% of the total emissions. From 1990 to 2007, annual
      SO(2) emission was fluctuated with two peaks (1996 and 2006), and total emission
      doubled from 15.4 Tg to 30.8 Tg, at an annual growth rate of 4.4% (6.3% since
      2000). Due to the extensive application of FGD technology and the phase-out of
      small, high emitting units, the SO(2) emission began to decrease after 2006.
      Furthermore, the differences among estimates reported in literatures highlight a
      great need for further research to reduce the uncertainties with more detailed
      information on key sources and actual operation of devices.

PMID- 21851094
TI  - Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase
      IX and XII inhibitors.
AB  - Carbonic anhydrase (CA) enzymes, specifically membrane-bound isozymes CA IX and
      CA XII, underpin a pH-regulating system that enables hypoxic tumor cell survival
      and proliferation. CA IX and XII are implicated as potential targets for the
      development of new hypoxic cancer therapies. To date, only a few small molecules
      have been characterized in CA-relevant cell and animal model systems. In this
      paper, we describe the development of a new class of carbohydrate-based small
      molecule CA inhibitors, many of which inhibit CA IX and XII within a narrow range
      of low nanomolar K(i) values (5.3-11.2 nM). We evaluate for the first time
      carbohydrate-based CA inhibitors in cell-based models that emulate the protective
      role of CA IX in an acidic tumor microenvironment. Our findings identified two
      inhibitors (compounds 5 and 17) that block CA IX-induced survival and have
      potential for development as in vivo cancer cell selective inhibitors.

PMID- 21851095
TI  - Thermal dehydration of monohydrocalcite: overall kinetics and physico-geometrical
      mechanisms.
AB  - Monohydrocalcite (CaCO(3).H(2)O: MHC) is similar in composition and synthetic
      conditions to hydrated amorphous calcium carbonate (ACC), which is focused
      recently as a key intermediate compound of biomineralization and biomimetic
      mineralization of calcium carbonate polymorphs. Detailed comparisons of the
      physicochemical property and reactivity of those hydrated calcium carbonates are
      required for obtaining fundamental information on the relevancy of those
      compounds in the mineralization processes. In the present study, kinetics of the
      thermal dehydration of spherical particles of crystalline MHC was investigated in
      view of physico-geometrical mechanism. The reaction process was traced
      systematically by means of thermogravimetry under three different modes of
      temperature program. A distinguished induction period for the thermal dehydration
      and cracking of the surface product layer on the way of the established reaction
      were identified as the characteristic events of the reaction. By interpreting the
      kinetic results in association with the morphological changes of the reactant
      particles during the course of reaction, it was revealed that nucleation and
      crystal growth of calcite regulate the overall kinetics of the thermal
      dehydration of MHC. In comparison with the thermal dehydration of hydrated ACC,
      which produces anhydrous ACC as the solid product, the kinetic characteristics of
      the thermal dehydration of MHC were discussed from the viewpoint of physico
      geometry of the component processes.

PMID- 21851096
TI  - High content screening in zebrafish speeds up hazard ranking of transition metal
      oxide nanoparticles.
AB  - Zebrafish is an aquatic organism that can be used for high content safety
      screening of engineered nanomaterials (ENMs). We demonstrate, for the first time,
      the use of high content bright-field and fluorescence-based imaging to compare
      the toxicological effect of transition metal oxide (CuO, ZnO, NiO, and Co(3)O(4))
      nanoparticles in zebrafish embryos and larvae. High content bright-field imaging
      demonstrated potent and dose-dependent hatching interference in the embryos, with
      the exception of Co(3)O(4) which was relatively inert. We propose that the
      hatching interference was due to the shedding of Cu and Ni ions, compromising the
      activity of the hatching enzyme, ZHE1, similar to what we previously proposed for
      Zn(2+). This hypothesis is based on the presence of metal-sensitive histidines in
      the catalytic center of this enzyme. Co-introduction of a metal ion chelator,
      diethylene triamine pentaacetic acid (DTPA), reversed the hatching interference
      of Cu, Zn, and Ni. While neither the embryos nor larvae demonstrated
      morphological abnormalities, high content fluorescence-based imaging demonstrated
      that CuO, ZnO, and NiO could induce increased expression of the heat shock
      protein 70:enhanced green fluorescence protein (hsp70:eGFP) in transgenic
      zebrafish larvae. Induction of this response by CuO required a higher
      nanoparticle dose than the amount leading to hatching interference. This response
      was also DTPA-sensitive. We demonstrate that high content imaging of embryo
      development, morphological abnormalities, and HSP70 expression can be used for
      hazard ranking and determining the dose-response relationships leading to ENM
      effects on the development of the zebrafish embryo.

PMID- 21851097
TI  - Characterization of new potential anticancer drugs designed to overcome
      glutathione transferase mediated resistance.
AB  - Resistance against anticancer drugs remains a serious obstacle in cancer
      treatment. Here we used novel strategies to target microsomal glutathione
      transferase 1 (MGST1) and glutathione transferase pi (GSTP) that are often
      overexpressed in tumors and confer resistance against a number of cytostatic
      drugs, including cisplatin and doxorubicin (DOX). By synthetically combining
      cisplatin with a GST inhibitor, ethacrynic acid, to form ethacraplatin, it was
      previously shown that cytosolic GST inhibition was improved and that cells became
      more sensitive to cisplatin. Here we show that ethacraplatin is easily taken up
      by the cells and can reverse cisplatin resistance in MGST1 overexpressing MCF7
      cells. A second and novel strategy to overcome GST mediated resistance involves
      using GST releasable cytostatic drugs. Here we synthesized two derivatives of
      DOX, 2,4-dinitrobenzenesulfonyl doxorubicin (DNS-DOX) and 4
      mononitrobenzenesulfonyl doxorubicin (MNS-DOX) and showed that they are
      substrates for MGST1 and GSTP (releasing DOX). MGST1 overexpressing cells are
      resistant to DOX. The resistance is partially reversed by DNS-DOX. Interestingly,
      the less reactive MNS-DOX was more cytotoxic to cells overexpressing MGST1 than
      control cells. It would appear that, by controlling the reactivity of the
      prodrug, and thereby the DOX release rate, selective toxicity to MGST1
      overexpressing cells can be achieved. In the case of V79 cells, DOX resistance
      proportional to GSTP expression levels was noted. In this case, not only was drug
      resistance eliminated by DNS-DOX but a striking GSTP-dependent increase in
      toxicity was observed in the clonogenic assay. In summary, MGST1 and GSTP
      resistance to cytostatic drugs can be overcome and cytotoxicity can be enhanced
      in GST overexpressing cells.

PMID- 21851098
TI  - Comparative studies on thermochemical characterization of corn stover pretreated
      by white-rot and brown-rot fungi.
AB  - The effects of white-rot and brown-rot fungal pretreatment on the chemical
      composition and thermochemical conversion of corn stover were investigated.
      Fungus-pretreated corn stover was analyzed by Fourier transform infrared
      spectroscopy and X-ray diffraction analysis to characterize the changes in
      chemical composition. Differences in thermochemical conversion of corn stover
      after fungal pretreatment were investigated using thermogravimetric and pyrolysis
      analysis. The results indicated that the white-rot fungus Irpex lacteus CD2 has
      great lignin-degrading ability, whereas the brown-rot fungus Fomitopsis sp. IMER2
      preferentially degrades the amorphous regions of the cellulose. The
      biopretreatment favors thermal decomposition of corn stover. The weight loss of
      IMER2-treated acid detergent fiber became greater, and the oil yield increased
      from 32.7 to 50.8%. After CD2 biopretreatment, 58% weight loss of acid detergent
      lignin was achieved and the oil yield increased from 16.8 to 26.8%.

PMID- 21851100
TI  - Human lysozyme possesses novel antimicrobial peptides within its N-terminal
      domain that target bacterial respiration.
AB  - Human milk lysozyme is thought to be a key defense factor in protecting the
      gastrointestinal tract of newborns against bacterial infection. Recently,
      evidence was found that pepsin, under conditions relevant to the newborn stomach,
      cleaves chicken lysozyme (cLZ) at specific loops to generate five antimicrobial
      peptide motifs. This study explores the antimicrobial role of the corresponding
      peptides of human lysozyme (hLZ), the actual protein in breast milk. Five peptide
      motifs of hLZ, one helix-loop-helix (HLH), its two helices (H1 and H2), and two
      helix-sheet motifs, H2-beta-strands 1-2 (H2-S12) or H2-beta-strands 1-3 (H2-S13),
      were synthesized and examined for antimicrobial action. The five peptides of hLZ
      exhibit microbicidal activity to various degrees against several bacterial
      strains. The HLH peptide and its N-terminal helix (H1) were significantly the
      most potent bactericidal to Gram-positive and Gram-negative bacteria and the
      fungus Candida albicans . Outer and inner membrane permeabilization studies, as
      well as measurements of transmembrane electrochemical potentials, provided
      evidence that HLH peptide and its N-terminal helix (H1) kill bacteria by crossing
      the outer membrane of Gram-negative bacteria via self-promoted uptake and are
      able to dissipate the membrane potential-dependent respiration of Gram-positive
      bacteria. This finding is the first to describe that hLZ possesses multiple
      antimicrobial peptide motifs within its N-terminal domain, providing insight into
      new classes of antibiotic peptides with potential use in the treatment of
      infectious diseases.

PMID- 21851099
TI  - Chemical logic and enzymatic machinery for biological assembly of peptidyl
      nucleoside antibiotics.
AB  - Peptidyl nucleoside antibiotics are a group of natural products targeting MraY, a
      bacterial translocase involved in the lipid-linked cycle in peptidoglycan
      biosynthesis. In this Perspective, we explore how Nature builds complex peptidyl
      nucleoside antibiotics scaffolds from simple nucleoside and amino acid building
      blocks. We discuss the current stage of research on biosynthetic pathways for
      peptidyl nucleoside antibiotics, primarily focusing on chemical logic and
      enzymatic machinery for uridine transformation and coupling to peptides. We
      further survey the nonribosomal biosynthetic paradigm for a subgroup of uridyl
      peptide antibiotics represented by pacidamycins, concluded by diversification
      opportunities for antibiotic optimization.

PMID- 21851101
TI  - Improvement of hemocompatibility of polycaprolactone film surfaces with
      zwitterionic polymer brushes.
AB  - Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but
      further improvement of the hemocompatibility of a PCL film surface is still
      needed for wide biomedical applications. In this work, the PCL film surface was
      functionalized with zwitterionic poly(3-dimethyl(methacryloyloxyethyl) ammonium
      propane sulfonate) (P(DMAPS)) brushes via surface-initiated atom transfer radical
      polymerization (ATRP) for enhancing hemocompatibility. Kinetics study revealed an
      approximately linear increase in graft yield of the functional P(DMAPS) brushes
      with polymerization time. The blood compatibilities of the modified PCL film
      surfaces were studied by platelet adhesion tests of platelet-rich plasma and
      human whole blood, hemolysis assay, and plasma recalcification time (PRT) assay.
      The improvement of hemocompatibility is dependent on the coverage of the grafted
      P(DMAPS) brushes on the PCL film. Lower or no platelet and blood cell adhesion
      was observed on the P(DMAPS)-grafted film surfaces. The P(DMAPS) grafting can
      further decrease hemolysis and enhance the PRT of the PCL surface. With the
      versatility of surface-initiated ATRP and the excellent hemocompatibility of
      zwitterionic polymer brushes, PCL films with desirable blood properties can be
      readily tailored to cater to various biomedical applications.

PMID- 21851102
TI  - Effect of temperature on PV potential in the world.
AB  - This work aims to identify the geographic distribution of photovoltaic (PV)
      energy potential considering the effect of temperature on PV system performance.
      A simple framework is developed that uses the JIS C 8907 Japanese industrial
      standard to evaluate the effects of irradiation and temperature on PV potential.
      The global distributions of PV potential and yearly performance ratio are
      obtained by this framework. Generally, the performance ratio decreases with
      latitude because of temperature. However, regions with high altitude have higher
      performance ratios due to low temperature. The southern Andes, the Himalaya
      region, and Antarctica have the largest PV potentials. Although PV modules with
      less sensitivity to temperature are preferable for the high temperature regions,
      PV modules that are more responsive to temperature may be more effective in the
      low temperature regions. The correlation between the estimates obtained by our
      framework and results from a more data-intensive method increases when the
      temperature effects are considered.

PMID- 21851104
TI  - In vivo targeted delivery of nanoparticles for theranosis.
AB  - Therapy and diagnosis are two major categories in the clinical treatment of
      disease. Recently, the word "theranosis" has been created, combining the words to
      describe the implementation of these two distinct pursuits simultaneously. For
      successful theranosis, the efficient delivery of imaging agents and drugs is
      critical to provide sufficient imaging signal or drug concentration in the
      targeted disease site. To achieve this purpose, biomedical researchers have
      developed various nanoparticles composed of organic or inorganic materials.
      However, the targeted delivery of these nanoparticles in animal models and
      patients remains a difficult hurdle for many researchers, even if they show
      useful properties in cell culture condition.  In this Account, we review our
      strategies for developing theranostic nanoparticles to accomplish in vivo
      targeted delivery of imaging agents and drugs. By applying these rational
      strategies, we achieved fine multimodal imaging and successful therapy. Our first
      strategy involves physicochemical optimization of nanoparticles for long
      circulation and an enhanced permeation and retention (EPR) effect. We
      accomplished this result by testing various materials in mouse models and
      optimizing the physical properties of the materials with imaging techniques.
      Through these experiments, we developed a glycol chitosan nanoparticle (CNP),
      which is suitable for angiogenic diseases, such as cancers, even without an
      additional targeting moiety. The in vivo mechanism of this particle was examined
      through rationally designed experiments. In addition, we evaluated and compared
      the biodistribution and target-site accumulation of bare and drug-loaded
      nanoparticles.  We then focus on the targeting moieties that bind to cell surface
      receptors. Small peptides were selected as targeting moieties because of their
      stability, low cost, size, and activity per unit mass. Through phage display
      screening, the interleukin-4 receptor binding peptide was discovered, and we
      combined it with our nanoparticles. This product accumulated efficiently in
      atherosclerotic regions or tumors during both imaging and therapy. We also
      developed hyaluronic acid nanoparticles that can bind efficiently to the CD44
      antigen receptors abundant in many tumor cells. Their delivery mechanism is based
      on both physicochemical optimization for the EPR effect and receptor-mediated
      endocytosis by their hyaluronic acid backbone.  Finally, we introduce the stimuli
      responsive system related to the chemical and biological changes in the target
      disease site. Considering the relatively low pH in tumors and ischemic sites, we
      applied pH-sensitive micelle to optical imaging, magnetic resonance imaging,
      anticancer drug delivery, and photodynamic therapy. In addition, we successfully
      evaluated the in vivo imaging of enzyme activity at the target site with an
      enzyme-specific peptide sequence and CNPs.  On the basis of these strategies, we
      were able to develop self-assembled nanoparticles for in vivo targeted delivery,
      and successful results were obtained with them in animal models for both imaging
      and therapy. We anticipate that these rational strategies, as well as our
      nanoparticles, will be applied in both the diagnosis and therapy of many human
      diseases. These theranostic nanoparticles are expected to greatly contribute to
      optimized therapy for individual patients as personalized medicine, in the near
      future.

PMID- 21851105
TI  - Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced
      graphene oxide: membrane and oxidative stress.
AB  - Health and environmental impacts of graphene-based materials need to be
      thoroughly evaluated before their potential applications. Graphene has strong
      cytotoxicity toward bacteria. To better understand its antimicrobial mechanism,
      we compared the antibacterial activity of four types of graphene-based materials
      (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene
      oxide (rGO)) toward a bacterial model-Escherichia coli. Under similar
      concentration and incubation conditions, GO dispersion shows the highest
      antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning
      electron microscope (SEM) and dynamic light scattering analyses show that GO
      aggregates have the smallest average size among the four types of materials. SEM
      images display that the direct contacts with graphene nanosheets disrupt cell
      membrane. No superoxide anion (O(2)(*-)) induced reactive oxygen species (ROS)
      production is detected. However, the four types of materials can oxidize
      glutathione, which serves as redox state mediator in bacteria. Conductive rGO and
      Gt have higher oxidation capacities than insulating GO and GtO. Results suggest
      that antimicrobial actions are contributed by both membrane and oxidation stress.
      We propose that a three-step antimicrobial mechanism, previously used for carbon
      nanotubes, is applicable to graphene-based materials. It includes initial cell
      deposition on graphene-based materials, membrane stress caused by direct contact
      with sharp nanosheets, and the ensuing superoxide anion-independent oxidation. We
      envision that physicochemical properties of graphene-based materials, such as
      density of functional groups, size, and conductivity, can be precisely tailored
      to either reducing their health and environmental risks or increasing their
      application potentials.

PMID- 21851106
TI  - Bead-based competitive fluorescence immunoassay for sensitive and rapid diagnosis
      of cyanotoxin risk in drinking water.
AB  - Due to the increased occurrence of cyanobacterial blooms and their toxins in
      drinking water sources, effective management based on a sensitive and rapid
      analytical method is in high demand for security of safe water sources and
      environmental human health. Here, a competitive fluorescence immunoassay of
      microcystin-LR (MCYST-LR) is developed in an attempt to improve the sensitivity,
      analysis time, and ease-of-manipulation of analysis. To serve this aim, a bead
      based suspension assay was introduced based on two major sensing elements: an
      antibody-conjugated quantum dot (QD) detection probe and an antigen-immobilized
      magnetic bead (MB) competitor. The assay was composed of three steps: the
      competitive immunological reaction of QD detection probes against analytes and MB
      competitors, magnetic separation and washing, and the optical signal generation
      of QDs. The fluorescence intensity was found to be inversely proportional to the
      MCYST-LR concentration. Under optimized conditions, the proposed assay performed
      well for the identification and quantitative analysis of MCYST-LR (within 30 min
      in the range of 0.42-25 MUg/L, with a limit of detection of 0.03 MUg/L). It is
      thus expected that this enhanced assay can contribute both to the sensitive and
      rapid diagnosis of cyanotoxin risk in drinking water and effective management
      procedures.

PMID- 21851107
TI  - Thyroid axis disruption in juvenile brown trout (Salmo trutta) exposed to the
      flame retardant beta-tetrabromoethylcyclohexane (beta-TBECH) via the diet.
AB  - Tetrabromoethylcyclohexane (TBECH) is an additive brominated flame retardant used
      in domestic and industrial applications. It has been detected in wildlife, and
      there is early evidence that it is an endocrine disruptor. Whereas other
      brominated flame retardants with similar physicochemical properties have been
      shown to disrupt the thyroid axis, no such evaluation has been conducted for
      TBECH. To elucidate this, juvenile brown trout (Salmo trutta) were fed either a
      control diet or diets containing low, medium, or high doses of beta-TBECH, the
      isomer most frequently detected in wildlife, for 56 days (uptake phase) followed
      by a control diet for an additional 77 days (depuration phase). Eight fish per
      treatment were lethally sampled on uptake days 7, 14, 21, 35, 49, and 56 and on
      depuration days 7, 21, 35, 49, and 77 to assess fish condition, circulating free
      and total triiodothyronine and thyroxine, and thyroid epithelial cell height.
      Although there was no effect on condition factor, there was a significant
      reduction in total plasma thyroxine in the high dose group and a significant
      increase in mean thyroid epithelial cell height in the low, medium, and high dose
      groups during the uptake phase, whereas there were no differences in the
      depuration phase. These results indicate that beta-TBECH may modulate the thyroid
      axis in fish at environmentally relevant concentrations.

PMID- 21851108
TI  - Highly sensitive plasmonic silver nanorods.
AB  - We compare the single-particle plasmonic sensitivity of silver and gold nanorods
      with similar resonance wavelengths by monitoring the plasmon resonance shift upon
      changing the environment from water to 12.5% sucrose solution. We find that
      silver nanoparticles have 1.2 to 2 times higher sensitivity than gold, in good
      agreement with simulations based on the boundary-elements-method (BEM). To
      exclude the effect of particle volume on sensitivity, we test gold rods with
      increasing particle width at a given resonance wavelength. Using the Drude-model
      of optical properties of metals together with the quasi-static approximation
      (QSA) for localized surface plasmons, we show that the dominant contribution to
      higher sensitivity of silver is the lower background polarizability of the d-band
      electrons and provide a simple formula for the sensitivity. We improve the
      reversibility of the silver nanorod sensors upon repeated cycles of environmental
      changes by blocking the high energy parts of the illumination light.

PMID- 21851109
TI  - Blue flickers of hope: secondary structure, dynamics, and putative dimerization
      interface of the blue-light receptor YtvA from Bacillus subtilis.
AB  - Bacillus subtilis is capable of responding to various kinds of extracellular,
      potentially harmful stimuli via a stress response pathway, which involves a
      signal transduction and integration hub, the stressosome, and finally leads to
      activation of sigma(B). One of the different signals initiating the underlying
      phosphorylation cascade is blue light. While it is known that the bacterial
      photoreceptor YtvA is responsible for blue light detection, the intramolecular
      activation mechanism and the structure of this multidomain protein are unknown.
      Using solution NMR spectroscopy, we have obtained a near complete backbone
      assignment of the full-length protein. More importantly, we report relaxation
      data and data on the solvent accessibility of full-length YtvA in the dark state
      which are interpreted with respect to secondary structure, the mobility, and the
      quaternary structure of the protein. Finally, we show that YtvA adopts an
      elongated domain orientation with LOV-LOV and STAS-STAS interactions on either
      side.

PMID- 21851110
TI  - One-pot two-component [3 + 2] cycloaddition/annulation protocol for the synthesis
      of highly functionalized thiophene derivatives.
AB  - An efficient and experimentally rapid protocol for the synthesis of hitherto
      unreported 2,3-dicarboalkoxy-4-aroyl/heteroaroyl/alkanoyl thiophenes has been
      developed via 1-2 (C-S) and 3-4 (C-C) bond connections promoted by 4
      dimethylaminopyridine (DMAP). Optimally, the reaction takes only 3-5 min when
      beta-oxodithioester and dialkyl acetylenedicarboxylate are stirred in DCM at room
      temperature in the presence of DMAP. This method allows a clean and general
      synthesis of previously inaccessible and synthetically demanding thiophenes
      containing the ferrocenyl group. The speed, experimental ease, and high yields of
      this process are improvements over existing methods to access this important
      substructure.

PMID- 21851111
TI  - Scan-rate-dependent ion current rectification and rectification inversion in
      charged conical nanopores.
AB  - Herein we report a theoretical study of diode-like behavior of negatively charged
      (e.g., glass or silica) nanopores at different potential scan rates (1-1000 V.s(
      1)). Finite element simulations were used to determine current-voltage
      characteristics of conical nanopores at various electrolyte concentrations. This
      study demonstrates that significant changes in rectification behavior can be
      observed at high scan rates because the mass transport of ionic species appears
      sluggish on the time scale of the voltage scan. In particular, it explains the
      influence of the potential scan rate on the nanopore rectifying properties in the
      cases of classical rectification, rectification inversion, and the "transition"
      rectification domain where the rectification direction in the nanopore could be
      modulated according to the applied scan rate.

PMID- 21851113
TI  - Energetics of halogen bonding of group 10 metal fluoride complexes.
AB  - A study is presented of the thermodynamics of the halogen-bonding interaction of
      C(6)F(5)I with a series of structurally similar group 10 metal fluoride complexes
      trans-[Ni(F)(2-C(5)NF(4))(PCy(3))(2)] (2), trans-[Pd(F)(4-C(5)NF(4))(PCy(3))(2)]
      (3), trans-[Pt(F){2-C(5)NF(2)H(CF(3))}(PR(3))(2)] (4a, R = Cy; 4bR = iPr) and
      trans-[Ni(F){2-C(5)NF(2)H(CF(3))}(PCy(3))(2)] (5a) in toluene solution. (19)F NMR
      titration experiments are used to determine binding constants, enthalpies and
      entropies of these interactions (2.4 <= K(300) <= 5.2; -25 <= DeltaH(o) <= -16 kJ
      mol(-1); -73 <= DeltaS(o) <= -49 J K(-1) mol(-1)). The data for -DeltaH(o) for
      the halogen bonding follow a trend Ni < Pd < Pt. The fluoropyridyl ligand is
      shown to have a negligible influence on the thermodynamic data, but the influence
      of the phosphine ligand is significant. We also show that the value of the spin
      spin coupling constant J(PtF) increases substantially with adduct formation. X
      ray crystallographic data for Ni complexes 5a and 5c are compared to previously
      published data for a platinum analogue. We show by experiment and computation
      that the difference between Pt-X and Ni-X (X = F, C, P) bond lengths is greatest
      for X = F, consistent with F(2ppi)-Pt(5dpi) repulsive interactions. DFT
      calculations on the metal fluoride complexes show the very negative electrostatic
      potential around the fluoride. Calculations of the enthalpy of adduct formation
      show energies of -18.8 and -22.8 kJ mol(-1) for Ni and Pt complexes of types 5
      and 4, respectively, in excellent agreement with experiment.

PMID- 21851114
TI  - Nanopatterning of fluorinated graphene by electron beam irradiation.
AB  - We demonstrate the possibility to selectively reduce insulating fluorinated
      graphene to conducting and semiconducting graphene by electron beam irradiation.
      Electron-irradiated fluorinated graphene microstructures show 7 orders of
      magnitude decrease in resistivity (from 1 TOmega to 100 kOmega), whereas
      nanostructures show a transport gap in the source-drain bias voltage. In this
      transport gap, electrons are localized, and charge transport is dominated by
      variable range hopping. Our findings demonstrate a step forward to all-graphene
      transparent and flexible electronics.

PMID- 21851115
TI  - Two new cluster ions, Ga[GaH3]4(5-) with a neopentane structure in Rb8Ga5H15 and
      [GaH2]n(n-) with a polyethylene structure in Rb(n)(GaH2)n, represent a new class
      of compounds with direct Ga-Ga bonds mimicking common hydrocarbons.
AB  - The first examples of a new class of gallium hydride clusters with direct Ga-Ga
      bonds and common hydrocarbon structures are reported. Neutron powder diffraction
      was used to find a Ga[GaH(3)](4)(5-) cluster ion with a neopentane structure in a
      novel cubic structure type of Rb(8)Ga(5)H(15). Another cluster ion with a
      polyethylene structure, [GaH(2)](n)(n-), was found in a second novel
      (RbGaH(2))(n) hydride. These hydrocarbon-like clusters in gallium hydride
      materials have significant implications for the discovery of hydrides for
      hydrogen storage as well as for interesting electronic properties.

PMID- 21851116
TI  - Design of chemical shift-switching 19F magnetic resonance imaging probe for
      specific detection of human monoamine oxidase A.
AB  - Monoamine oxidase (MAO) A is a flavoenzyme that catalyzes the oxidation of
      biologically important monoamines and is thought to be associated with
      psychiatric disorders. Here, we report a strategy for rationally designing a
      (19)F magnetic resonance imaging probe for the specific detection of human MAO-A
      (hMAO-A) activity. Our designed (19)F probe was oxidized expeditiously by hMAO-A
      to produce 2-fluoro-4-nitrophenol via a spontaneous beta-elimination mechanism.
      Concomitant with the structural change of the probe to the product, the (19)F
      chemical shift changed by 4.2 ppm, which was enough to visualize the probe and
      enzymatic product separately. Importantly, our probe achieved excellent
      discrimination of hMAO-A from its isoform hMAO-B.

PMID- 21851117
TI  - Mechanistic elucidation of intramolecular aminoalkene hydroamination catalyzed by
      a tethered bis(ureate) complex: evidence for proton-assisted C-N bond formation
      at zirconium.
AB  - A broad mechanistic investigation regarding hydroamination reactions catalyzed by
      a tethered bis(ureate) zirconium species, [ureate(2-)]Zr(NMe(2))(2)(HNMe(2)), is
      described. The cyclization of both primary and secondary aminoalkene substrates
      gives similar kinetic profiles, with zero-order dependence on substrate
      concentration up to ~60-75% conversion, followed by first-order dependence for
      the remainder of the reaction. The addition of 2-methylpiperidine changes the
      observed substrate dependence to first order throughout the reaction, but does
      not act as a competitive inhibitor. The reactions are first order in precatalyst
      up to loadings of ~0.15 M, indicating that a well-defined, mononuclear catalytic
      species is operative. Several model complexes have been structurally
      characterized, including dimeric imido and amido species, and evaluated for
      catalytic performance. These results indicate that imido species need not be
      invoked as catalytically relevant intermediates, and that the mono(amido) complex
      [ureate(2-)]Zr(NMe(2))(Cl)(HNMe(2)) is much less active than its bis(amido)
      counterpart. Structural evidence suggests that this is due to differences in
      coordination geometry between the mono- and bis(amido) complexes, and that an
      equatorial amido ligand is required for efficient catalytic turnover. On the
      basis of the determination of kinetic isotope effects and stoichiometric
      reactivity, the catalytic turnover-limiting step is proposed to be a concerted C
      H, C-N bond-forming process with a highly ordered, unimolecular transition state
      (DeltaS(?) = -21 +/- 1 eu). In addition to this key bond-forming step, the
      catalytic cycle involves an on-cycle pre-equilibrium between six- and seven
      coordinate intermediates, leading to the observed switch from zero- to first
      order kinetics.

PMID- 21851118
TI  - Through-bond interactions and the localization of excited-state dynamics.
AB  - The influence of through-bond interactions on nonadiabatic excited-state dynamics
      is investigated by time-resolved photoelectron spectroscopy (TRPES) and ab initio
      computation. We compare the dynamics of cyclohexa-1,4-diene, which exhibits a
      through-bond interaction known as homoconjugation (the electronic correlation
      between nonconjugated double bonds), with the nonconjugated cyclohexene. Each
      molecule was initially excited to a 3s Rydberg state using a 200 nm femtosecond
      pump pulse. The TRPES spectra of these molecules display similar structure and
      time constants on a subpicosecond time scale. Our ab initio calculations show
      that similar sets of conical intersections (a [1,2]- and [1,3]-hydrogen shift, as
      well as carbon-carbon bond cleavage) are energetically accessible to both
      molecules and that the geometry and orbital composition at the minimum energy
      crossing points to the ground state are directly analogous. These experimental
      and computational results suggest that the excited-state dynamics of cyclohexa
      1,4-diene become localized at a single double bond and that the effects of
      through-bond interaction, dominant in the absorption spectrum, are absent in the
      excited-state dynamics. The notion of excited-state dynamics being localized at
      specific sites within the nuclear framework is analogous to the localization of
      light absorption by a subsystem within the molecule, designated a chromophore. We
      propose the utility of the analogous concept, denoted here as a dynamophore.

PMID- 21851120
TI  - One-pot synthesis of quinazolinones via iridium-catalyzed hydrogen transfers.
AB  - A one-pot oxidative cyclization of primary alcohols with o-aminobenzamides to
      quinazolinones was successfully achieved using [Cp*IrCl(2)](2) (Cp* =
      pentamethylcyclopentadienyl) as a catalyst under hydrogen transfer conditions.

PMID- 21851119
TI  - Development and application of a multimodal contrast agent for SPECT/CT hybrid
      imaging.
AB  - Hybrid or multimodality imaging is often applied in order to take advantage of
      the unique and complementary strengths of individual imaging modalities. This
      hybrid noninvasive imaging approach can provide critical information about
      anatomical structure in combination with physiological function or targeted
      molecular signals. While recent advances in software image fusion techniques and
      hybrid imaging systems have enabled efficient multimodal imaging, accessing the
      full potential of this technique requires development of a new toolbox of
      multimodal contrast agents that enhance the imaging process. Toward that goal, we
      report the development of a hybrid probe for both single photon emission computed
      tomography (SPECT) and X-ray computed tomography (CT) imaging that facilitates
      high-sensitivity SPECT and high spatial resolution CT imaging. In this work, we
      report the synthesis and evaluation of a novel intravascular, multimodal
      dendrimer-based contrast agent for use in preclinical SPECT/CT hybrid imaging
      systems. This multimodal agent offers a long intravascular residence time (t(1/2)
      = 43 min) and sufficient contrast-to-noise for effective serial intravascular and
      blood pool imaging with both SPECT and CT. The colocalization of the dendritic
      nuclear and X-ray contrasts offers the potential to facilitate image analysis and
      quantification by enabling correction for SPECT attenuation and partial volume
      errors at specified times with the higher resolution anatomic information
      provided by the circulating CT contrast. This may allow absolute quantification
      of intramyocardial blood volume and blood flow and may enable the ability to
      visualize active molecular targeting following clearance from the blood.

PMID- 21851121
TI  - Interfacial morphology and photoelectrochemistry of conjugated polyelectrolytes
      adsorbed on single crystal TiO2.
AB  - The nanoscale morphology and photoactivity of conjugated polyelectrolytes (CPEs)
      deposited from different solvents onto single crystal TiO(2) were investigated
      with atomic force microscopy (AFM) and photocurrent spectroscopy. CPE surface
      coverages on TiO(2) could be incremenentally increased by adsorbing the CPEs from
      static solutions. The solvents used for polymer adsorption influenced the surface
      morpohology of the CPEs on the TiO(2) surface. Photocurrent spectroscopy
      measurements in aqueous electrolytes, using iodide as a hole scavenger, revealed
      that the magnitude of the sensitized photocurrents was related to the surface
      coverages and the degree of aggregation of the CPEs as determined by AFM imaging.
      Absorbed photon-to-current efficiencies approaching 50% were measured for CPE
      layers as thick as 4 nm on TiO(2). These results suggest that precise control of
      CPE morphology at the TiO(2) interface can be achieved through optimization of
      the deposition conditions to improve the power conversion efficiencies of polymer
      sensitized solar cells.

PMID- 21851122
TI  - Error bounds on the SCISSORS approximation method.
AB  - The SCISSORS method for approximating chemical similarities has shown excellent
      empirical performance on a number of real-world chemical data sets but lacks
      theoretically proven bounds on its worst-case error performance. This paper first
      proves reductions showing SCISSORS to be equivalent to two previous kernel
      methods: kernel principal components analysis and the rank-k Nystrom
      approximation of a Gram matrix. These reductions allow the use of generalization
      bounds on these techniques to show that the expected error in SCISSORS
      approximations of molecular similarity kernels is bounded in expected pairwise
      inner product error, in matrix 2-norm and Frobenius norm for full kernel matrix
      approximations and in root-mean-square deviation for approximated matrices.
      Finally, we show that the actual performance of SCISSORS is significantly better
      than these worst-case bounds, indicating that chemical space is well-structured
      for chemical sampling algorithms.

PMID- 21851124
TI  - Electric field-driven extraction of lipophilic anions across a carrier-mediated
      polymer inclusion membrane.
AB  - The use of a cationic carrier-mediated polymer inclusion membrane (PIM) for
      extraction and preconcentration of anionic model analytes driven by an electric
      field directly into an aqueous acceptor solution is demonstrated. The optimized
      membrane was 20 MUm thick and consisted of 60% cellulose triacetate as base
      polymer, 20% o-nitrophenyl octyl ether as plasticizer, and 20% Aliquat 336 as
      cationic carrier in the perchlorate form. By applying voltages of up to 700 V
      across the membrane, the lipophilic model analytes propanesulfonate,
      octanesulfonate, and decanesulfonate could be transported from the aqueous donor
      solution to the aqueous acceptor solution with efficiences >90% within 5 to 20
      min. A preconcentration factor of 26, defined by the volume ratio between donor
      and acceptor compartments of the current cell design, could be achieved. The
      utility of the method for analytical applications is demonstrated by extraction
      of the herbicide glyphosate and its breakdown product aminomethylphosphonic acid
      from spiked river water, followed by quantification with capillary
      electrophoresis using contactless conductivity detection. Limits of detection of
      0.8 and 1.5 ng/mL were obtained for glyphosate and aminomethylphosphonic acid,
      respectively.

PMID- 21851123
TI  - Synthesis of cyclic enones via direct palladium-catalyzed aerobic dehydrogenation
      of ketones.
AB  - alpha,beta-Unsaturated carbonyl compounds are versatile intermediates in the
      synthesis of pharmaceuticals and biologically active compounds. Here, we report
      the discovery and application of Pd(DMSO)(2)(TFA)(2) as a catalyst for direct
      dehydrogenation of cyclohexanones and other cyclic ketones to the corresponding
      enones, using O(2) as the oxidant. The substrate scope includes heterocyclic
      ketones and several natural-product precursors.

PMID- 21851125
TI  - Antioxidant properties of chlorogenic acid and its alkyl esters in stripped corn
      oil in combination with phospholipids and/or water.
AB  - In bulk oil, it is generally thought that hydrophilic antioxidants are more
      active than lipophilic antioxidants. To test this hypothesis, the antioxidant
      activity of phenolics with increasing hydrophobicity was evaluated in stripped
      corn oil using both conjugated diene and hexanal measurements. Chlorogenic acid
      and its butyl, dodecyl, and hexadecyl esters were used as model phenolic
      antioxidants with various hydrophobicities. Results showed that hydrophobicity
      did not correlate well with antioxidant capacity. The combination of chlorogenic
      acid derivatives with dioleoylphosphatidylcholine (DOPC) and/or water was also
      studied to determine if the physical structure in the oil affected antioxidant
      activity. DOPC alone made hexadecyl chlorogenate a less effective antioxidant,
      but it did not change the antioxidant capacity of chlorogenic acid. In contrast,
      the combination of DOPC and water (~400 ppm) renders chlorogenic acid a less
      active antioxidant, whereas it does not change the activity of hexadecyl
      chlorogenate. These results show, in bulk oil, that intrinsic parameters such as
      the hydrophobicity of lipophilized phenolics do not exert a strong influence on
      antioxidant capacity, but they can be highly influential if potentialized by
      extrinsic factors such as physical structures in the oil.

PMID- 21851129
TI  - YouTube or you lose: Grand Challenges Canada explores whether scientists are
      ready for Web-based grant competitions.

PMID- 21851130
TI  - Cycloquest: identification of cyclopeptides via database search of their mass
      spectra against genome databases.
AB  - Hundreds of ribosomally synthesized cyclopeptides have been isolated from all
      domains of life, the vast majority having been reported in the last 15 years.
      Studies of cyclic peptides have highlighted their exceptional potential both as
      stable drug scaffolds and as biomedicines in their own right. Despite this,
      computational techniques for cyclopeptide identification are still in their
      infancy, with many such peptides remaining uncharacterized. Tandem mass
      spectrometry has occupied a niche role in cyclopeptide identification, taking
      over from traditional techniques such as nuclear magnetic resonance spectroscopy
      (NMR). MS/MS studies require only picogram quantities of peptide (compared to
      milligrams for NMR studies) and are applicable to complex samples, abolishing the
      requirement for time-consuming chromatographic purification. While database
      search tools such as Sequest and Mascot have become standard tools for the MS/MS
      identification of linear peptides, they are not applicable to cyclopeptides, due
      to the parent mass shift resulting from cyclization and different fragmentation
      patterns of cyclic peptides. In this paper, we describe the development of a
      novel database search methodology to aid in the identification of cyclopeptides
      by mass spectrometry and evaluate its utility in identifying two peptide rings
      from Helianthus annuus, a bacterial cannibalism factor from Bacillus subtilis,
      and a theta-defensin from Rhesus macaque.

PMID- 21851131
TI  - Dietary mercury has no observable effects on thyroid-mediated processes and
      fitness-related traits in wood frogs.
AB  - Mercury (Hg) is a neurotoxicant known to cause developmental and behavioral
      abnormalities in vertebrates. Increasing evidence suggests that Hg can also
      disrupt endocrine functions and endocrine-dependent processes. For example,
      dietary Hg has been shown to delay tail resorption during metamorphic climax in
      amphibians, a process mediated by thyroid hormones. However, a direct link
      between Hg, hormone disruption, and developmental delays in amphibians has not
      been explored. Therefore, we examined the effects of dietary Hg (0.01, 2.5, and
      10 MUg/g total Hg, dry wt) on thyroid hormone concentrations, development,
      growth, performance, and survival of wood frogs (Rana sylvatica). Tadpoles
      accumulated Hg in a concentration-dependent manner; total Hg concentrations in
      tadpoles at the beginning of metamorphic climax (Gosner stage 42) were 0.03,
      1.06, 3.54 MUg/g, dry wt, for control, low, and high Hg diets, respectively.
      During metamorphic climax, tadpoles eliminated 35% of the inorganic Hg from their
      tissues but retained most of their accumulated methylmercury. Contrary to our
      predictions, we found no effect of Hg on the duration of tadpole development,
      size at metamorphosis, tail resorption time, or hopping performance. Consistent
      with the lack of effects on development, we also detected no differences in whole
      body thyroid hormone concentrations among our dietary treatments. Our results,
      when compared with the effects of Hg on other amphibians, suggest that amphibian
      species may differ substantially in their sensitivity to dietary Hg, emphasizing
      the need for data on multiple species when establishing toxicity benchmarks.

PMID- 21851132
TI  - What else can the analysis of sewage for urinary biomarkers reveal about
      communities?

PMID- 21851133
TI  - Unusual cold crystallization behavior in physically aged poly(L-lactide).
AB  - A comparative study of cold crystallization behavior in poly(L-lactide) (PLLA)
      annealed below and just above the glass transition temperature (T(g)) has been
      conducted. Annealing benefits the generation of local order and the subsequent
      cold crystallization process, which becomes significant in PLLA annealed just
      above T(g). Surprisingly, morphological observation reveals high density nuclei
      in PLLA annealed below T(g), contrary to its relatively slow crystallization
      kinetics. This unusual crystallization behavior in physically aged PLLA arises
      from the retarded crystal growth rate because of incomplete recovery of reduced
      segmental mobility above T(g). In contrast, annealing just above T(g) has little
      influence on the crystal growth rate, and the increased nucleation density alone
      accounts for the accelerated crystallization rate.

PMID- 21851134
TI  - Isolation and identification of flavonoids accumulated in proanthocyanidin-free
      barley.
AB  - Flavonoids accumulated in proanthocyanidin-free near-isogenic lines iso ant 13,
      iso ant 17, and iso ant 22 of Nishinohoshi, developed by backcross breeding using
      a leading cultivar, Nishinohoshi, as a recurrent parent and a proanthocyanidin
      free mutant as a nonrecurrent parent in Japan, were examined. A new flavanone,
      (2RS)-dihydrotricin 7-O-beta-D-glucopyranoside (1), known flavanones (2RS)
      dihydrotricin (2) and (2RS)-homoeriodictyol (3), and known flavones chrysoeriol 7
      O-[alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside] (4), chrysoeriol 7-O
      beta-D-glucopyranoside (5), tricin (6), and chrysoeriol (7) were isolated from
      iso ant 17 of Nishinohoshi. The structures and stereochemistries of the isolated
      flavonoids (1-7) were elucidated on the basis of spectroscopic analyses. The
      concentrations of the isolated flavonoids (1-7) in iso ant 13, iso ant 17, and
      iso ant 22 of Nishinohoshi were similar to each other, whereas the flavonoids 1-5
      and 7 were not detected in Nishinohoshi, an old Japanese cultivar, Amaginijo, and
      North American cultivar Harrington. The concentration of tricin (6) in
      Nishinohoshi was a half those in iso ant 13, iso ant 17, and iso ant 22 of
      Nishinohoshi. Except for iso ant 13, iso ant 17, and iso ant 22 of Nishinohoshi,
      the concentration of tricin (6) was highest in Nishinohoshi, followed by
      Amaginijo and Harrington. Thus, tricin (6), its precursor dihydrotricin (2), and
      its glucopyranoside, dihydrotricin 7-O-beta-D-glucopyranoside (1), as well as
      chrysoeriol (7) and homoeriodictyol (3) were accumulated in iso ant 13, iso ant
      17, and iso ant 22 of Nishinohoshi probably by blocking at the step of flavanone
      3-hydroxylase in the procyanidin biogenetic pathway, resulting in enhancement of
      the alternative biogenetic pathway.

PMID- 21851136
TI  - Lynch syndrome screening implementation: business analysis by a healthcare
      system.
AB  - OBJECTIVE: To characterize the current state of evidence and apply simulation
      modeling to support decision making about provision and coverage of a Lynch
      syndrome (LS) screening program among colorectal cancer (CRC) patients in our
      integrated healthcare delivery system. STUDY DESIGN: Application of multiple
      methods for synthesizing evidence guided by needs of our clinical and
      administrative decision makers. METHODS: Narrative and focused reviews,
      computerized simulation models of multiple screening options, queries of our
      electronic data warehouse, and extensive communication with decision makers.
      RESULTS: Review of published evidence at the time of the study period revealed
      that screening unselected CRC patients for LS would likely cost less than $25,000
      per life-year saved (compared with no screening) and that screening with
      immunohistochemistry is substantially more efficient than other options. Our
      simulation models suggest that not only does including BRAF mutation testing
      substantially improve efficiency but that adding methylation testing improves it
      further. We characterized a variety of other metrics that contributed not only to
      local decisions but to the broader evidence base on this topic. CONCLUSION: The
      current state of evidence at the time of the study period suggests an LS
      screening program can be both effective in reducing mortality from CRC and cost
      effective. However, direct evidence remains limited and multiple factors could
      threaten success of such a program. We have identified opportunities for
      optimizing the efficiency of available screening protocols. While there was
      enough evidence for our system to proceed with an LS screening program, we
      recognize the threats to program success and will prospectively collect outcome
      data supporting empirical examination of the program.

PMID- 21851137
TI  - Classification of health plans based on relative resource use and quality of
      care.
AB  - OBJECTIVE: To examine variation among commercial health plans in resource use and
      quality of care for patients with diabetes mellitus or cardiovascular disease.
      STUDY DESIGN: Cohort study using Healthcare Effectiveness Data and Information
      Set data submitted to the National Committee for Quality Assurance in 2008.
      METHODS: Composite measures were estimated for diabetes and cardiovascular
      disease resource use and quality of care. A "value" classification approach was
      defined. Obtained were descriptive statistics, Pearson product moment
      correlations between resource use and quality of care, and 90% confidence
      intervals around each health plan's composite measures of resource use and
      quality of care. Health plans were classified based on their results. RESULTS:
      For patients with diabetes, the correlation between combined medical care
      services resource use and composite quality of care is negative (-0.201, p =
      .008); the correlation between ambulatory pharmacy services resource use and
      composite quality of care is positive (0.162, p = .03). For patients with
      cardiovascular disease, no significant correlation was found between combined
      medical care services resource use and composite quality of care (-0.007, p =
      .94) or ambulatory pharmacy services resource use (0.170, p = .06). CONCLUSIONS:
      Measures of resource use and quality of care provide important information about
      the value of a health plan. Although our analysis did not determine causality,
      the statistically weak or absent correlations between resource use and quality of
      care suggest that health plans and practices can create higher value by improving
      quality of care without large increases in resource use or by maintaining the
      same quality of care with decreased resource use.

PMID- 21851138
TI  - Value-based purchasing: the evidence.
AB  - OBJECTIVE: This report presents evidence about "what works" in value-based
      purchasing strategies emphasized in national healthcare reform legislation, with
      a focus on service delivery integration, payment, and value-based insurance
      design. We review key findings to address the question: What is the evidence that
      a value-based strategy will improve health outcomes or reduce healthcare costs?
      STUDY DESIGN: This report is a review of peer-reviewed and field-based research
      associated with several value-based strategies purchasers can use to increase
      value in their healthcare market decision making: Accountable Care Organizations,
      Patient Centered Medical Homes, bundled payment methods and incentives, and value
      based insurance designs. METHODS: Environmental scans and evidence reviews of
      value-based purchasing were conducted to inform this report. RESULTS: Many value
      based approaches are new to the healthcare arena, and evidence of performance in
      improving health outcomes or reducing healthcare costs is limited but increasing
      as experience with these approaches grows. CONCLUSIONS: Purchasers should be
      aware that evidence is contingent on market environment and study assumptions in
      considering specific strategies, and be cautious implementing them. The need for
      a new measurement paradigm for cost and quality that reaches across the care
      continuum is evident.

PMID- 21851139
TI  - Cost of post-traumatic stress disorder vs major depressive disorder among
      patients covered by medicaid or private insurance.
AB  - OBJECTIVE: To compare healthcare costs and resource utilization among patients
      with post-traumatic stress disorder (PTSD) vs control subjects with major
      depressive disorder (MDD) in populations covered by Medicaid or private
      insurance. STUDY DESIGN: Retrospective analysis of Medicaid and private insurance
      administrative claims data. METHODS: Patients with at least 2 PTSD diagnoses
      during or after 1999, and at least 1 PTSD diagnosis during or after 2003, were
      identified from deidentified Medicaid claims from Florida, Missouri, and New
      Jersey (1999-2007) and from a privately insured claims database (1999-2008).
      Patients had continuous eligibility 6 months before (baseline) and 12 months
      after (study period) the index date and were aged 18 to 64 years. Potential
      control subjects having MDD without PTSD diagnosis were identified using similar
      selection criteria. Control subjects with MDD were matched to patients with PTSD
      on age, sex, state or region, employment status (private insurance only), index
      year, and race/ethnicity (Medicaid only). Study period per-patient utilization
      and costs, calculated as reimbursements to providers for medical services and
      prescription drugs, were compared using univariate and multivariate analyses.
      RESULTS: Patients with PTSD had higher rates of other mental health disorders
      (eg, anxiety and bipolar disorder) and higher mental health-related resource use
      and costs than control subjects with MDD in both Medicaid and privately insured
      populations. The mean study period total direct healthcare costs were higher for
      patients with PTSD than for control subjects with MDD ($18,753 vs $17,990 for
      Medicaid and $10,960 vs $10,024 for private insurance, P <.05 for both). The
      difference in total direct costs was driven by higher mental health-related
      resource use for patients with PTSD. CONCLUSION: Patients having PTSD had 4.2% to
      9.3% higher mean annual per-patient healthcare costs compared with matched
      control subjects having MDD among patients covered by Medicaid or private
      insurance.

PMID- 21851140
TI  - Identifying subgroups of complex patients with cluster analysis.
AB  - OBJECTIVE: To illustrate the use of cluster analysis for identifying sub
      populations of complex patients who may benefit from targeted care management
      strategies. STUDY DESIGN: Retrospective cohort analysis. METHODS: We identified a
      cohort of adult members of an integrated health maintenance organization who had
      2 or more of 17 common chronic medical conditions and were categorized in the top
      20% of total cost of care for 2 consecutive years (n = 15,480). We used
      agglomerative hierarchical clustering methods to identify clinically relevant
      subgroups based on groupings of coexisting conditions. Ward's minimum variance
      algorithm provided the most parsimonious solution. RESULTS: Ward's algorithm
      identified 10 clinically relevant clusters grouped around single or multiple
      "anchoring conditions." The clusters revealed distinct groups of patients
      including: coexisting chronic pain and mental illness, obesity and mental
      illness, frail elderly, cancer, specific surgical procedures, cardiac disease,
      chronic lung disease, gastrointestinal bleeding, diabetes, and renal disease.
      These conditions co-occurred with multiple other chronic conditions. Mental
      health diagnoses were prevalent (range 28% to 100%) in all clusters. CONCLUSIONS:
      Data mining procedures such as cluster analysis can be used to identify discrete
      groups of patients with specific combinations of comorbid conditions. These
      clusters suggest the need for a range of care management strategies. Although
      several of our clusters lend themselves to existing care and disease management
      protocols, care management for other subgroups is less well-defined. Cluster
      analysis methods can be leveraged to develop targeted care management
      interventions designed to improve health outcomes.

PMID- 21851141
TI  - Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in
      uncontrolled hyperlipidemia patients.
AB  - OBJECTIVE: Treatment of dyslipidemia in high-risk patients specifies a low
      density lipoprotein (LDL) cholesterol <100 mg/dL. The efficacy of higher-potency
      regimens in clinical practice in patients who have not achieved their LDL goal on
      generic therapy is not well characterized. The primary objective of this study
      was to determine the LDL-lowering efficacy of higher-potency strategies
      (ezetimibe/simvastatin, rosuvastatin, and atorvastatin) in high-risk patients who
      were switched from simvastatin therapy. Secondary objectives were to evaluate
      patient adherence to these therapies, determine the efficacy of these
      interventions on other lipid parameters, and define the incidence of adverse
      effects. STUDY DESIGN: Retrospective data analysis derived from the Veterans
      Affairs Health Care System VISN 21 over a 3-year time period. METHODS: Lipid data
      were assessed prior to and within 2 to 6 months following the conversion from
      simvastatin. Adherence to therapy was determined by medication refill data.
      RESULTS: Treatment with ezetimibe/simvastatin resulted in significantly greater
      reductions in LDL compared with rosuvastatin or atorvastatin (37 vs 25 and 26
      mg/dL, respectively; P <0.05). Adherence to therapy was 51% of all patients
      studied. All treatments significantly lowered total cholesterol, high-density
      lipoprotein, and triglycerides when compared with simvastatin. There was no
      difference between treatment groups in the number of adverse events. CONCLUSIONS:
      At the doses used in this population, ezetimibe/simvastatin resulted in greater
      LDL reductions than rosuvastatin or atorvastatin. The clinical impact of these
      differences is as yet undetermined.

PMID- 21851142
TI  - HCV screening practices and prevalence in an MCO, 2000-2007.
AB  - BACKGROUND/OBJECTIVE: The Centers for Disease Control and Prevention recommends
      routine screening for the hepatitis C virus antibody (anti- HCV) among persons
      most likely to be infected. Little is known about anti-HCV screening and
      prevalence in routine practice settings. We studied anti-HCV screening rates,
      anti-HCV positivity, and demographic and risk factors associated with increased
      likelihood of anti-HCV screening or positivity in a managed care organization
      (MCO). METHODS: This was a retrospective observational study of 17-to-74-year-old
      MCO enrollees from 2000 to 2007 (N = 557,056; 1,949,499 enrollee years). The
      primary outcome measures were likelihood of anti-HCV screening and HCV positivity
      (both in the total population and among those screened). Independent variables
      were: birth cohort, gender, HCV risk factors, and socioeconomic status (SES) and
      race of residents' neighborhoods. Likelihood of each outcome as a function of the
      independent variables was estimated using logistic regression. RESULTS: Over the
      8-year period, 4.31% of the total population received anti-HCV screening; 0.22%
      had a positive HCV result. Among those screened, HCV positivity was 5.15%. HCV
      screening and positivity rates increased over time. Both likelihood of HCV
      screening and HCV positivity were highest (P <0.05) among persons born during
      1945-1964, males, those with HCV risk factors, and residents of neighborhoods of
      lower SES or with higher percentages of African Americans. CONCLUSIONS: Although
      HCV screening and detection improved in this MCO over an 8-year period, anti-HCV
      screening was lower than expected. Many persons at risk for HCV remained
      unscreened. Strategies for improving anti-HCV screening in routine practice are
      recommended for patients at increased risk.

PMID- 21851143
TI  - Accountable care organizations: the proposed regulations and the prospects for
      success.
AB  - The 2010 Patient Protection and Affordable Care Act included a provision to
      promote the formation of Accountable Care Organizations (ACOs). These
      organizations will be eligible to share in the savings to Medicare if they are
      able to reduce costs and provide high-quality care. The law allows a wide variety
      of organizations to become ACOs, even networks of providers that are small
      compared with major integrated delivery networks. The Center for Medicare and
      Medicaid Services recently proposed regulations, which are extensive and complex.
      They impose significant regulatory requirements on these new organizations,
      ranging from the structure of the organization to quality standards for
      qualifying for any shared savings. There are a number of challenges to ACOs and
      it is uncertain whether they can achieve the goals Congress had in mind or even
      whether many healthcare provider organizations will be interested in
      participating in the program. The potential for shared savings may be too small
      to justify the additional costs and regulatory burdens of becoming an ACO. In
      addition, the incentives to physicians may be inadequate to encourage behavior
      that reduces cost while maintaining quality. The article reviews the proposed
      regulations and discusses the prospects for success of ACOs.

PMID- 21851144
TI  - Diabetes and employment productivity: does diabetes management matter?
AB  - OBJECTIVE: To determine whether labor market effects were the result of diabetes
      per se or rather depended on the degree to which diabetes was controlled through
      management of blood sugar levels. METHODS: This study utilized data from a
      recently completed survey of households in Brownsville, Texas, a largely Mexican
      American community with a high prevalence of diabetes that is located on the
      Texas-Mexico border. Diabetes management, or control, was measured by blood sugar
      levels, glycosylated hemoglobin (A1C) levels, and interaction terms. Methods used
      were probit and Heckman regression. RESULTS: Management of diabetes did not
      appear to have a discernible impact on labor market outcomes in the short run.
      However, diabetes was negatively associated with male productivity, particularly
      in males' propensity to work. The new American Diabetes Association (ADA)
      definition of diabetes is based on having an A1C level of <6.5%. Using the new
      ADA definition, diabetes was negatively associated with female productivity.
      Female productivity was also negatively associated with the new ADA definition of
      prediabetes (A1C levels between 5.7% and 6.4%). However, very few people with
      diabetes actually controlled their blood sugar or A1C levels. CONCLUSION: These
      results imply that in order to avoid productivity losses associated with
      diabetes, more scarce prevention resources should be spent on prevention of the
      onset of diabetes than on the management of A1C for those already diagnosed with
      diabetes. For women, the prevention of prediabetes is key.

PMID- 21851145
TI  - The FLU-FIT program: an effective colorectal cancer screening program for high
      volume flu shot clinics.
AB  - OBJECTIVE: To determine whether offering home fecal immunochemical tests (FITs)
      to eligible patients during a high volume influenza vaccination clinic could lead
      to increased colorectal cancer screening (CRCS) rates in a managed care setting.
      STUDY DESIGN: Observational study. METHODS: During influenza vaccination clinics
      in 2008, trained staff provided FITs to patients who were eligible for CRCS (FLU
      FIT group) (FLU indicates influenza vaccine). Screening outcomes for this cohort
      of patients were compared with those of a similar group of influenza clinic
      attendees who were not exposed to the intervention (FLUonly group). RESULTS:
      Among eligible participants in the FLU-only group (N = 4653), 13.7% completed FIT
      within 90 days of their influenza vaccine, and in the FLU-FIT group (N = 2812),
      30.3% completed FIT (P <.0001). In the FLU-FIT group, 1447 (51.4%) were provided
      with a FIT kit, and 653 (45.1%) of these patients completed a FIT kit within 90
      days. In multivariate analyses, FLU-FIT group participants were significantly
      more likely to complete FITs compared with FLU-only group participants (Odds
      Ratio = 2.76 [95% confidence interval, 2.45-3.11]). Overall, the CRCS rate for
      the FLU-only group increased from 51.5% to 56.3% (increase of 4.8 percentage
      points), compared with an increase from 49.2% to 63.2% (increase of 14.0
      percentage points) in the FLU-FIT group (P lt;.0001 for change difference).
      CONCLUSIONS: The FLU-FIT Program is feasible to implement in a high volume
      influenza vaccination clinic conducted in a managed care setting and increases
      colorectal cancer screening activity among eligible influenza vaccination
      recipients who are reached with the intervention.

PMID- 21851146
TI  - Genotoxic and cytotoxic activity of host defense peptides against human soft
      tissue sarcoma in an in vitro model.
AB  - Soft tissue sarcomas (STSs) are a heterogeneous group of rare, mesenchymal
      tumors. Treatment with common chemotherapeutic drugs is consistently associated
      with low response rates and high rates of adverse toxic effects. Host defense
      peptides (HDPs) are used as part of innate immunity, and many of them act by
      directly lysing the target cell membrane. Studies have demonstrated high
      selectivity of HDP analogs against malignant cells because of a relative
      abundance of negative charges in malignant cell membranes, compared to normal
      cells. Our aim was to assess the toxic efficacy of [D]-K(6)L(9), [D]
      K(3)H(3)L(9), and Protegrin-1 against the fibrosarcoma cell line, HT1080, and
      primary human fibroblasts to analyze the potential of these peptides as
      therapeutic options against STSs. Cell proliferation of the fibrosarcoma cell
      line, HT1080, and human fibroblasts was determined in vitro after treatment with
      [D]-K(6)L(9), [D]-K(3)H(3)L(9), and Protegrin-1. Genotoxicity was examined on the
      basis of the mild alkali version of single-cell gel electrophoresis (comet
      assay). Doxorubicin, a commonly used STS chemotherapeutic agent, served as the
      control. The native HDP, Protegrin-1, could show a cytotoxic tendency against
      malignant cells, but no selectivity in genotoxic trials. The synthetic peptide,
      [D]-K(6)L(9), could not show any selective oncolytic activity against sarcoma
      cells. [D]-K(3)H(3)L(9) has shown a tendency for toxic selectivity against
      malignant cells. There is a potential of developing suitable oncolytic candidates
      with selectivity against malignant cells. [D]-K(3)H(3)L(9) showed the first
      promising results, but there has to be further investigation to improve the
      therapeutic properties of HDPs.

PMID- 21851147
TI  - Evidence that process simulations reduce anxiety in patients receiving dental
      treatment: randomized exploratory trial.
AB  - Process simulations--mental simulations that ask people to imagine the process of
      completing a task--have been shown to decrease anxiety in students facing
      hypothetical or psychological threats in the short term. The aim of the present
      study was to see whether process simulations could reduce anxiety in a sample of
      the general population attending a dental practice, and whether these effects
      could be sustained throughout treatment. Participants (N=75) were randomized to
      an experimental condition where they were asked to simulate mentally the process
      of seeing the dentist, or to a control condition where they were asked to
      simulate mentally the outcome of seeing the dentist. Findings showed that
      participants in the experimental condition were significantly less anxious both
      before and after their consultations. Self-efficacy and self-esteem remained
      unchanged. This study suggests that process simulation is one active ingredient
      in anxiety treatment programs and further research is required to enhance its
      effects.

PMID- 21851148
TI  - Antimycobacterial activity of steroids, long-chain alcohols and lytic peptides.
AB  - As a continuation of our project aimed at a search for new antimycobacterial
      agents, several naturally occurring and synthetic compounds have been evaluated
      against Mycobacterium tuberculosis H37Rv and M. avium. Emphasis was placed on
      steroids and a series of isoprene long-chain alcohols to gain new insight into
      their structural activities. Maximum activity of isoprenoid derivatives seemed to
      depend on the hydrophobic chain length from the hydrophilic hydroxyl moiety. In
      contrast, ergosterol peroxide produced significantly greater inhibition than the
      corresponding steroids. Bile acids, amino acid-based surfactants and cholesteryl
      esters possessing different alkyl side chains were surprisingly the least
      effective. Encapsulation of compounds in cyclodextrins did not lead to
      significant loss in activity. Considering the inhibitory activity observed for
      the active steroids and isoprene long-chain alcohols, the phytyl moiety appeared
      to be critical for maximum activity. The implications of these findings for the
      rational design of new antituberculosis agents are briefly discussed.

PMID- 21851149
TI  - Variation in working memory capacity and cognitive control: goal maintenance and
      microadjustments of control.
AB  - Variation in working memory capacity (WMC) and cognitive control was examined in
      four experiments. In the experiments high- and low-WMC individuals performed a
      choice reaction time task (Experiment 1), a version of the antisaccade task
      (Experiment 2), a version of the Stroop task (Experiment 3), and an arrow version
      of the flanker task (Experiment 4). An examination of response time distributions
      suggested that high- and low-WMC individuals primarily differed in the slowest
      responses in each experiment, consistent with the notion that WMC is related to
      active maintenance abilities. Examination of two indicators of microadjustments
      of control (posterror slowing and conflict adaptation effects) suggested no
      differences between high- and low-WMC individuals. Collectively these results
      suggest that variation in WMC is related to some, but not all, cognitive control
      operations. The results are interpreted within the executive attention theory of
      WMC.

PMID- 21851150
TI  - Directed forgetting of faces: the role of response criterion.
AB  - In two experiments, we examined recognition for faces following item method
      directed forgetting. During testing, participants reported whether the face was a
      new face or, if they thought it was a studied face, they identified the
      instruction paired with the face during study. In both experiments, the
      proportion of new faces falsely recognized and classified as forget faces
      exceeded those falsely recognized and classified as remember faces. Despite the
      use of different response criteria during testing, participants showed greater
      discrimination accuracy when identifying remember faces than when identifying
      forget faces. Taken together, these data patterns indicate that participants
      employed a strength-based criterion when responding. Specifically, participants
      responding to new faces were more likely to classify those faces as forget faces
      from study rather than as remember faces from study.

PMID- 21851151
TI  - Visual attention to emotion in depression: facilitation and withdrawal processes.
AB  - Attentional biases for sadness are integral to cognitive theories of depression,
      but do not emerge under all conditions. Some researchers have argued that
      depression is associated with delayed withdrawal from, but not facilitated
      initial allocation of attention toward, sadness. We compared two types of
      withdrawal processes in clinically depressed and non-depressed individuals: (1)
      withdrawal requiring overt eye movements during visual search; and (2) covert
      disengagement of attention in a modified cueing paradigm. We also examined
      initial allocation of attention towards emotion on the visual search task,
      allowing comparison of withdrawal and facilitation processes. As predicted, we
      found no evidence of facilitated attention towards sadness in depressed
      individuals. However, we also found no evidence of depression-linked differences
      in withdrawal of attention from sadness on either task, offering no support for
      the theory that depression is associated with withdrawal rather than initial
      facilitation of attention.

PMID- 21851152
TI  - Differential impacts of age of acquisition on letter and semantic fluency in
      Alzheimer's disease patients and healthy older adults.
AB  - The degree to which the typical age of acquisition (AoA) of words and word
      frequency have separable influences on verbal production tasks has been strongly
      debated. To examine the overlap between these factors in verbal fluency tasks,
      the performance of Alzheimer's disease (AD) patients (N = 34) and normal elderly
      controls (N = 36) was compared on semantic (e.g., vegetables) and letter (e.g.,
      words that begin with F) fluency tasks. These comparisons revealed that words
      generated for the semantic fluency task had an earlier AoA while words generated
      for the letter fluency task had a higher word frequency. Differences in AoA
      between AD patients and controls were larger for semantic than letter fluency.
      These results suggest that AoA has an effect on verbal production that is
      independent of word frequency and that AoA has a semantic locus.

PMID- 21851153
TI  - Einstellung defused: Interactivity and mental set.
AB  - Mental set is observed when a familiar problem-solving strategy is applied to new
      problems that can be solved in simpler, more efficient ways. It is most famously
      illustrated in the water jar problems (Luchins,  1942 ). In these volume
      measurement problems, participants learn a rule to obtain an exact volume of
      liquid involving a complex combination of liquid transfer. Participants persevere
      in using this rule for new problems that can be solved with a much simpler rule.
      In two experiments presented here, participants completed the water jar task
      either in interactive conditions with actual water jars at a sink or in
      noninteractive conditions, with the problems presented on paper, as in the
      original Luchins procedure. Interactivity significantly reduced the degree of
      perseverance. In addition, participants' visuospatial skills significantly
      predicted the rate of perseverance (and the latencies to solution) in interactive
      but not in noninteractive conditions. These results underscore the importance of
      designing problem-solving experiments that engineer distributed cognitive systems
      in which participants coordinate internal and external resources in thinking.

PMID- 21851154
TI  - Do (un)certainty appraisal tendencies reverse the influence of emotions on risk
      taking in sequential tasks?
AB  - According to the Appraisal-Tendency Framework (Han, Lerner, & Keltner, 2007),
      certainty-associated emotions increase risk taking compared with uncertainty
      associated emotions. To date, this general effect has only been shown in static
      judgement and decision-making paradigms; therefore, the present study tested the
      effect of certainty on risk taking in a sequential decision-making task. We
      hypothesised that the effect would be reversed due to the kind of processing
      involved, as certainty is considered to encourage heuristic processing that takes
      into account the emotional cues arising from previous decisions, whereas
      uncertainty leads to more systematic processing. One hundred and one female
      participants were induced to feel one of three emotions (film clips) before
      performing a decision-making task involving risk (Game of Dice Task; Brand et
      al., 2005). As expected, the angry and happy participants (certainty-associated
      emotions) were more likely than the fearful participants (uncertainty-associated
      emotion) to make safe decisions (vs. risky decisions).

PMID- 21851155
TI  - ATRX in chromatin assembly and genome architecture during development and
      disease.
AB  - The regulation of genome architecture is essential for a variety of fundamental
      cellular phenomena that underlie the complex orchestration of mammalian
      development. The ATP-dependent chromatin remodeling protein ATRX is emerging as a
      key regulatory component of nucleosomal dynamics and higher order chromatin
      conformation. Here we provide an overview of the role of ATRX at chromatin and
      during development, and discuss recent studies exposing a repertoire of ATRX
      functions at heterochromatin, in gene regulation, and during mitosis and meiosis.
      Exciting new progress on several fronts suggest that ATRX operates in histone
      variant deposition and in the modulation of higher order chromatin structure. Not
      surprisingly, dysfunction or absence of ATRX protein has devastating consequences
      on embryonic development and leads to human disease.

PMID- 21851157
TI  - Laparoscopic management of congenital H-type urethroanal fistula.
AB  - Laparoscopic management in a case of congenital urethroanal fistula with a normal
      anterior urethra in a 5-month-old male child is reported. A congenital H-type
      urethroanal fistula is a rare entity. Management of such fistula has always been
      surgical, ranging from perineal dissection, posterior saggital approach, to
      abdomino-perineal approach. We describe a minimally invasive laparoscopic method
      for approaching such fistula, which has not been described in the literature and
      is being reported for the first time.

PMID- 21851159
TI  - Reflections of space exploration and its impact on telemedicine.

PMID- 21851158
TI  - Work-related asthma in Washington State.
AB  - OBJECTIVE: Asthma is a common and costly public health problem. Occupational
      exposures contribute to the burden of asthma. Identifying workplace exposures and
      industries and occupations at risk can lead to more effective prevention
      measures. METHODS: Data from Washington State's work-related asthma (WRA)
      surveillance program from October 2001 to December 2008 were analyzed. Workers'
      compensation records, physician reports, and telephone interviews were used to
      describe the occurrence of WRA during this time, in order to identify
      contributing exposure sources and industries and occupations that are associated
      with WRA in Washington. RESULTS: There were 1343 identified WRA cases in
      Washington State during this time. Of these, 1285 were workers' compensation
      claims, with a total medical cost for State Fund claims of approximately $3
      million dollars. The top three sources identified were miscellaneous chemicals
      and materials, mineral and inorganic dusts, and plant material. Plant material
      claims proved to be widespread throughout various industries, were largely
      classified as new-onset asthma cases, and had higher median medical cost and
      higher median time loss days than cases associated with other exposure sources.
      CONCLUSIONS: Washington State has an abundance of plant-material-related WRA
      cases among US states conducting WRA surveillance. Washington State's industry
      mix might explain the higher prevalence of cases, particularly its logging and
      wood processing industries and as a world leader in hops production. In
      Washington, further WRA prevention efforts should emphasize workplaces working
      with plant materials.

PMID- 21851160
TI  - An architecture for cross-hospital access to electrocardiogram data.
AB  - Owing to a lack of easy access to an individual's electrocardiogram (ECG) data
      that may be distributed across multiple hospitals, medical practice using serial
      ECG analysis has not so far been extensively used. Motivated to address this
      problem, we design and implement an architecture for cross-hospital access to ECG
      data. The architecture provides a Web portal for retrieving a particular
      patient's ECG data distributed across a number of ECG data sources. Two important
      features of this architecture are (1) the distributed search mechanism that uses
      a master patient index to determine what ECG data sources are likely to contain
      the ECG data pertaining to a specified patient and (2) the Web service-based
      interoperable method for accessing disparate ECG data sources. We show that the
      architecture provides an effective search and retrieval facility for cross
      hospital access to ECG data; we show this by implementing and employing a
      prototype in an experimental scenario consisting of two disparate ECG data
      sources located at two sites. Our study demonstrates a significant effort to
      improve the ease of cross-hospital access to ECG data.

PMID- 21851161
TI  - Reproducibility of telecytology diagnosis of cervical smears in a quality
      assurance program: the Georgian experience.
AB  - OBJECTIVE: The study evaluated the reproducibility of telecytology diagnosis of
      cervical smears on a randomly selected 50 cases under the conditions of Georgia.
      MATERIALS AND METHODS: Fifty cervical smears (benign, 14; atypical squamous cells
      of undetermined significance [ASCUS], 14; low-grade squamous intraepithelial
      lesion [LSIL], 10; high-grade squamous intraepithelial lesion [HSIL], 12) were
      selected. The digital images were captured at a maximum resolution of 2048 * 1536
      pixels and transmitted by electronic mail. Diagnosis of glass slides and digital
      images was done independently in a double-blind manner by three cytologists,
      versus the diagnosis of digital images followed by diagnosis of glass slides 3
      months later. The procedure was repeated after 3 months. RESULTS: Diagnoses were
      recorded as benign, ASCUS, LSIL, and HSIL. Diagnostic accuracy and interobserver
      reproducibility were analyzed using an interclass correlation coefficient, which
      revealed good interobserver agreement for the first (0.82) and second (0.68)
      glass slide diagnoses and the first (0.80) and second (0.66) digital image
      diagnoses. The kappa values for interobserver variation between first and second
      glass slide diagnoses and first and second digital image diagnoses showed good to
      excellent agreement. CONCLUSIONS: Digital images are suitable substitutes for
      glass slides; telecytology can be used as an alternative method for the cytologic
      diagnosis of cervical smears, particularly in quality assurance programs.

PMID- 21851156
TI  - Cohesin: a critical chromatin organizer in mammalian gene regulation.
AB  - Cohesins are evolutionarily conserved essential multi-protein complexes that are
      important for higher-order chromatin organization. They play pivotal roles in the
      maintenance of genome integrity through mitotic chromosome regulation, DNA repair
      and replication, as well as gene regulation critical for proper development and
      cellular differentiation. In this review, we will discuss the multifaceted
      functions of mammalian cohesins and their apparent functional hierarchy in the
      cell, with particular focus on their actions in gene regulation and their
      relevance to human developmental disorders.

PMID- 21851162
TI  - In vitro kinetics of oxygen transport in erythrocyte suspension or unmodified
      hemoglobin solution from human and other animals.
AB  - Oxygen transport behavior in erythrocyte suspension or in hemoglobin solution was
      studied as a potential therapeutic model for the clinical treatment of blood
      loss, and this can also provide physiological data with which to evaluate blood
      substitutes. In the present project, we examined the in vitro kinetics of
      hemoglobin binding to and releasing oxygen, to provide detailed oxygen-flux
      measurements for unmodified hemoglobin solutions and erythrocyte suspensions in
      human, as well as other vertebrates. An in vitro method was used, based on a
      widely used artificial system, with the oxygen saturation level being detected in
      real time. Results from this study indicated that the kinetic curves of human
      erythrocyte suspensions and hemoglobin solutions were either S-shaped or
      hyperbolic, respectively. Based on these curves, the significance of T(50)
      emerged in our investigation, where T(50) is defined as the time needed for 50%
      hemoglobin to be saturated with oxygen, and reflects the efficiency with which
      hemoglobin carries oxygen. This parameter may be used to diagnose blood diseases,
      and could be a standard for evaluating blood substitutes. In this study, we also
      compared the T(50) of 4 species of vertebrates, and found that it shows a
      distinct efficiency of oxygen binding related to species, and potentially reveals
      the evolutionary function of hemoglobin and its possible adaptation to the
      environment.

PMID- 21851163
TI  - Evidence of the influence of physical activity on the metabolic syndrome and/or
      on insulin resistance in pediatric populations: a systematic review.
AB  - This study is aimed at updating the relationships between physical activity (PA)
      and the metabolic syndrome (MetS) and/or insulin resistance (IR) in youth. Cross
      sectional, prospective cohort and intervention studies, which examined the effect
      of PA on MetS, its components and IR in children and adolescents (<18 yrs), were
      searched by applying a combination of criteria in the PubMed database. The
      electronic search of studies published from 2000-2010 yielded >150 references. Of
      these, 37 studies were included. Twenty-six studies (70%) were cross-sectional
      observation studies, and two studies (8%) were prospective cohort studies. The
      remaining eight studies (22%) were interventions, of which three (<10% of all
      included studies) were randomized controlled trials. Commonly, higher PA levels
      were consistently associated with an improved metabolic profile and a reduced
      risk for MetS and/or IR in these populations. The impact of PA on MetS and/or IR
      appeared to be either independent of other factors, or alternatively or
      simultaneously mediated by the physical fitness and adiposity of youth. However,
      more-robustly designed interventions (i.e., some mega-randomized controlled
      trials based on lifestyle interventions) and additional cohort studies are
      required to make definitive inference about the magnitude and role of PA as a
      single genuine preventive and treatment strategy for the metabolic and
      cardiovascular risk of youth in the current obesogenic context.

PMID- 21851164
TI  - Stability of epitheliotrophic factors in autologous serum eye drops from chronic
      Stevens-Johnson syndrome dry eye compared to non-autoimmune dry eye.
AB  - PURPOSE: To compare the concentrations of epitheliotrophic factors in autologous
      serum eye drops (ASE) prepared from sera of chronic Stevens-Johnson syndrome
      (SJS) patients with dry eyes to those prepared from non-autoimmune dry eye
      controls and to study the stability of the epitheliotrophic factors in different
      storage conditions. METHODS: Twenty-percent ASE were prepared from 10 chronic SJS
      patients with dry eyes and 10 age-matched non-autoimmune dry eye controls. The
      concentrations of major epitheliotrophic factors comprising epidermal growth
      factor (EGF), transforming growth factor-beta1 (TGF-beta1), transforming growth
      factor-beta2 (TGF-beta2), and fibronectin in those ASE preparations were
      determined by enzyme-linked immunosorbent assay (ELISA) at baseline and after
      different storage conditions: at 4  degrees C for 1 week and 1 month; and at -20 
      degrees C for 1, 3 and 6 months. RESULTS: There were no significant differences
      in the concentrations of EGF, TGF-beta1, TGF-beta2 and fibronectin in 20% ASE
      between the SJS and control groups (EGF: 176.9 +/- 40.9 vs. 185.5 +/- 36.9 pg/mL,
      TGF-beta1: 9.5 +/- 2.1 vs. 9.5 +/- 1.9 ng/mL, TGF-beta2: 55.3 +/- 30.0 vs. 63.91
      +/- 45.6 pg/mL and fibronectin: 70.5 +/- 20.2 vs. 62.2 +/- 21.3 ug/mL,
      respectively). These factors were stable at 4  degrees C for up to 1 month.
      Storage at -20  degrees C for up to 6 months resulted in a slight decrease in TGF
      beta1 (SJS: from 9.5-8.4 ng/mL, p < 0.01 and control: from 9.5-8.1 ng/mL, p <
      0.01). CONCLUSIONS: The results suggested that the epitheliotrophic capacity of
      ASE from chronic SJS should be comparable to those from non-autoimmune dry eye
      patients, and that ASE should be sufficiently stable for up to 6 months, if
      stored properly at -20  degrees C.

PMID- 21851165
TI  - Evaluation of conjunctival graft thickness after pterygium surgery by anterior
      segment optical coherence tomography.
AB  - BACKGROUND: To evaluate changes in thickness of the conjunctival graft after
      pterygium surgery by anterior segment optical coherence tomography (AS-OCT).
      MATERIALS AND METHODS: Eleven eyes of 11 patients with primary nasal pterygium
      underwent excision followed by free conjunctival autograft. Imaging with AS-OCT
      was performed at 1 week, 1 month and 3 months after surgery to measure thickness
      of the conjunctival graft at 1, 2 and 3 mm posterior to the scleral spur. As the
      control, thickness of the normal bulbar conjunctival epithelium in the temporal
      area was also measured at the same locations. RESULTS: Average thickness of the
      graft decreased from 458 +/- 171 um at 1 week after surgery to 306 +/- 64 um at 1
      month (p < 0.0001). Although the graft thickness decreased to 291 +/- 124 um at 3
      months postoperatively, the difference between 1-month and 3-month values was not
      statistically significant (p = 0.94). Average thickness of the normal
      conjunctival epithelium was 58 +/- 13 um, 60 +/- 19 um and 61 +/- 12 um at 1
      week, 1 month and 3 months after surgery, respectively, with no statistically
      significant difference. Graft thickness was significantly greater than thickness
      of the normal conjunctival epithelium at various time points (p < 0.05).
      CONCLUSION: Evaluation by AS-OCT showed that there was significant thickening of
      the conjunctival graft at 1 week after pterygium surgery which continued to
      decrease up to 3 months. Quantitative data by AS-OCT allows accurate evaluation
      of the conjunctival changes over time.

PMID- 21851166
TI  - Diurnal intraocular pressure efficacy of the timolol-brimonidine fixed
      combination and the timolol-dorzolamide fixed combination as a first choice
      therapy in patients with pseudoexfoliation glaucoma.
AB  - PURPOSE: To evaluate the 6- month daytime efficacy of a fixed combination of
      timolol and brimonidine (BTFC) versus a timolol and dorzolamide fixed combination
      (DTFC) as a first choice therapy in patients with pseudoexfoliation glaucoma
      (PXG). METHODS: This study was a randomized, prospective, investigator-masked, 6
      month comparison of twice-daily administration of BTFC versus DTFC in 60 newly
      diagnosed PXG patients. RESULTS: Mean baseline untreated IOPs were 25.5 +/- 2.6
      mmHg and 26.2 +/- 2.1 mmHg in the DTFC and BTFC groups, respectively. Mean
      intraocular pressure (IOP) reductions ranged from -7.3 +/- 1.9 to -8.1 +/- 2.0
      mmHg for the DTFC group and from -7.5 +/- 2.0 to -8.6 +/- 2.6 mmHg for the BTFC
      group. No significant differences between the two treatment groups could be
      found. At month 6, the mean diurnal IOP was 17.5 +/- 2.5 mmHg (31.3%) for the
      DTFC group and 18.0 +/- 2.8 mm Hg (31.7%) for BTFC. As compared with baseline,
      mean diurnal IOP decreased by 7.9 +/- 1.9 mmHg in the DTFC and 8.2 +/- 1.5 mmHg
      in the BTFC, the difference between the groups was not statistically significant
      (p = 0.6). No statistical difference in terms of adverse events was found either.
      CONCLUSION: Both fixed combinations were effective at lowering IOP in PXG. This
      study suggests that the daytime diurnal IOP is not statistically different when
      DTFC or BTFC is used as a first choice therapy in patients with PXG.

PMID- 21851167
TI  - A phase 2, randomized, dose-response trial of taprenepag isopropyl (PF-04217329)
      versus latanoprost 0.005% in open-angle glaucoma and ocular hypertension.
AB  - PURPOSE: To evaluate the safety of escalating doses of taprenepag isopropyl (PF
      04217329), a selective EP(2) receptor agonist administered as a topical
      ophthalmic solution, versus its vehicle (Stage I), and dose-response of
      taprenepag isopropyl alone and in unfixed combination with latanoprost ophthalmic
      solution 0.005% versus latanoprost alone (Stage II). SUBJECTS AND METHODS:
      Randomized, vehicle- and active-controlled, double-masked, two-stage, dose
      finding trial in primary open-angle glaucoma (POAG) or ocular hypertension; first
      taprenepag isopropyl study in patients (NCT00572455). Study eye: 26 mmHg <=
      intraocular pressure (IOP) <36 mmHg at 8 am and 22 mmHg <= IOP <36 mmHg at 10 am,
      1 pm, 4 pm. Stage I: 3 cohorts (total n = 67) received 1 drop of taprenepag
      isopropyl unit dose formulation qPM/eye for 14 days: low dose: 0.0025%, 0.005%,
      vehicle; middle dose: 0.01%, 0.015%, vehicle; high dose: 0.02%, 0.03%, vehicle.
      Stage II: 7 groups (total n = 250) received 1 drop of taprenepag isopropyl
      multidose formulation qPM/eye for 28 days: 0.005%, 0.01%, 0.015% monotherapy;
      each in unfixed combination with latanoprost 0.005%, or latanoprost monotherapy.
      MAIN OUTCOMES: mean change in diurnal IOP, baseline to last visit; adverse
      events. RESULTS: Stage I at day 14: statistically significantly greater IOP
      reductions were observed at all taprenepag isopropyl doses versus vehicle. Stage
      II at day 28: statistically significantly greater IOP reductions were observed at
      all doses of the unfixed combination versus latanoprost monotherapy. At least 1
      treatment-emergent adverse event reported for 29/67 (43.3%) subjects in Stage I
      and 158/250 (63.2%) in Stage II. CONCLUSIONS: Taprenepag isopropyl significantly
      reduces IOP in POAG and ocular hypertension. Taprenepag isopropyl monotherapy is
      comparable to latanoprost 0.005% in reducing IOP. As demonstrated in this report,
      the activity of taprenepag isopropyl is additive to that of latanoprost 0.005%.
      Further studies are required to determine whether it shows similar additivity
      when administered with other ocular antihypertensive medications.

PMID- 21851168
TI  - Supraciliochoroidal fluid incidence at the early stage after trabeculectomy:
      study with anterior segment optical coherence tomography.
AB  - PURPOSE: To analyze the appearance of supraciliochoroidal fluid (SCF) within 1
      week after trabeculectomy with anterior segment optical coherence tomography (AS
      OCT), a high-resolution, non-contact detection method. METHODS: In this
      prospective, non-comparative study, AS-OCT was used to assess the incidence of
      SCF in 25 eyes of 22 glaucoma patients who underwent trabeculectomy. Eyes were
      examined for SCF before and at 1, 3 days, and 1 week after surgery. Eyes with SCF
      were additionally examined at 2, 3, 4, and 8 postoperative weeks. Eyes were
      examined for the intraocular pressure (IOP), central depth of anterior chamber,
      and anterior inflammation. RESULTS: None of the 25 eyes displayed preoperative
      SCF. Postoperative SCF was found in 19 eyes (76%), which first appeared on day 1
      (10/19), day 3 (5/19), or 1 week (4/19) after surgery. Diagnoses of the 19 eyes
      included primary open-angle glaucoma (8 eyes), chronic primary angle-closure
      glaucoma (5 eyes), acute primary angle closue glaucoma (5 eyes), and secondary
      glaucoma (1 eye). SCF was found in four (16 eyes, 84.2%), two (2 eyes, 10.5%), or
      one quadrant (1 eye, 5.3%). Most of the 19 eyes displayed grade I (10 eyes,
      52.6%) or grade II detachment (8 eyes, 42.1%), with 1 eye (5.3%) showing grade
      III detachment. The lowest IOP was lower in eyes with SCF (4.3 +/- 2.7 mmHg) than
      in those without (16.3 +/- 6.0 mmHg) (p = 0.000). The IOP rose from 7.55 +/- 4.33
      mmHg at SCF detection to 13.47 +/- 5.52 mmHg at SCF disappearance (p = 0.009).
      Most eyes (17 eyes, 89.5%) had displayed no SCF by week 4, but one eye still
      displayed SCF at 8 postoperative weeks. CONCLUSIONS: At the very early stages
      after trabeculectomy (within 1 postoperative week), SCF was detected frequently
      with AS-OCT. Compared with previous reports using other detection methods, AS-OCT
      diagnosed postoperative SCF more frequently and at earlier time points.

PMID- 21851169
TI  - Influence of glutathione on the electroretinogram in diabetic and non-diabetic
      rats.
AB  - AIMS: The purpose of this study was to investigate the influence of glutathione
      on the electroretinogram (ERG) in diabetic and non-diabetic rats. MATERIALS AND
      METHODS: Streptozotocin (STZ: 60 mg/kg) was injected into male RCC Wistar rats to
      induce hyperglycemia, with buffer instead of STZ injected into age-matched non
      diabetic controls. After 8 weeks, ERG measurements were obtained at seven
      different scotopic flash intensities on the two groups of anesthetized, dark
      adapted rats (controls, STZ). Following ERG measurements, eyes were enucleated
      for measurements of retinal/vitreous GSH and glutathione disulfide (GSSG).
      RESULTS: Diabetic rats produced delayed b-wave ERG signals (increased implicit
      times), but had normal a-wave and b-wave amplitudes, a-wave implicit times, and
      oscillatory potentials. No differences were observed in retinal GSH or GSSG
      between controls and diabetics; however, correlations between GSH and all ERG
      parameters (with the exception of b-wave implicit times) were noted, and were not
      significantly altered by the presence of hyperglycemia. CONCLUSIONS: GSH is
      likely to play an important role in retinal function as assessed by the ERG, with
      this role not substantially altered in rats diabetic for 8 weeks.

PMID- 21851170
TI  - Hypoxia specific SDF-1 expression by retinal pigment epithelium initiates bone
      marrow-derived cells to participate in Choroidal neovascularization in a laser
      induced mouse model.
AB  - PURPOSE: Choroidal neovascularization (CNV) is a major cause of vision loss in
      patients with age-related macular degeneration (AMD). Stromal cell-derived factor
      1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) plays a critical role in homing of
      bone marrow-derived cells (BMCs) to choroidal neovascularization (CNV). In this
      study, we investigated the contribution of hypoxia specific HIF-1alpha-induced
      SDF-1 expression in retinal pigment epithelium (RPE) cells and the potential role
      of SDF-1 in CNV formation. MATERIALS AND METHODS: Green fluorescent protein (GFP)
      chimeric mice were developed by transplanting bone marrow cells of gfp(+/+)
      transgenic mice to sublethally irradiated C57BL/6J mice. CNV was induced by laser
      photocoagulation. Ocular tissue was processed for immunofluorescence to detect
      HIF-1alpha and SDF-1 expression, and cell surface markers such as CXCR4, CD34 and
      CD31 and so on during CNV formation. In vitro, adult human RPE (hRPE) cells were
      cultured under conditions of chemical hypoxia using CoCl2 administration. And
      RNAi technique was used to knock down HIF-1alpha gene to observe the expression
      of HIF-1alpha and SDF-1 in hRPE cells. RESULTS: BMCs trafficked around laser
      lesion adjacent to RPE layer 4 h after laser photocoagulation, where SDF-1
      expression was relatively higher. With increasing expression of SDF-1, more BMCs
      were infiltrated into laser lesion to participate in CNV, and both reached peak
      at 3 d (p < 0.05). About 81% BMCs involved in CNV were CXCR4+. Many of them
      acquired the surface marker of endothelial precursor cells (CD34+) and
      endothelial cells (CD31+). The constituent ratio of CD34+ and CD31+ BMCs
      increased with SDF-1 expression. In vitro, we proved that hypoxia specific-HIF
      1alpha influenced SDF-1 expression in hRPE cells. CONCLUSIONS: These findings
      suggested that hypoxia-induced SDF-1 expression in RPE might be a critical
      initiator for recruitment of BMCs in CNV. SDF-1 might be another important factor
      in BMCs' differentiation into endothelial cells to participate in the CNV.

PMID- 21851171
TI  - Expression of aquaporins in the retina of diabetic rats.
AB  - PURPOSE/AIM: The development of retinal edema is the main reason of impaired
      vision in non-proliferative diabetic retinopathy. Water transport through
      aquaporins (AQPs) has been suggested to facilitate the development of ischemic
      edema in the retina. Here, we investigated whether experimental diabetic
      retinopathy in rats results in alterations of the AQP expression in the neural
      retina and retinal pigment epithelium (RPE). MATERIALS AND METHODS: Experimental
      diabetes in rats was induced by a single intravenous injection of streptozotocin
      (65 mg/kg body weight). The gene expression of AQPs in tissues from control and
      diabetic rats was examined by real-time RT-PCR. Retinal cryosections were
      immunostained against AQP5, 6, and 9. RESULTS: The total RNAs extracted from the
      neural retina and RPE contained gene transcripts for AQP0, 1, 3, 4, 5, 6, 8, 9,
      11, and 12. Experimental diabetes was associated with an upregulation of AQP1 in
      the neural retina, and of AQP5, 9, 11, and 12 in the RPE. Furthermore, diabetes
      was associated with a downregulation of AQP6 and AQP11 in the neural retina, and
      of AQP0 in the RPE. AQP5 and AQP9 immunolabelings of the RPE were increased, and
      AQP6 labeling of the outer plexiform layer was decreased in retinal slices from
      diabetic rats in comparison to slices from control rats. CONCLUSIONS: The data
      suggest that experimental diabetic retinopathy is associated with a complex
      pattern of alteration in the retinal AQP expression. These alterations might be
      involved in the adaptation of retinal cells to hyperglycemic conditions and the
      development and/or resolution of retinal edema.

PMID- 21851174
TI  - Progress...but speed is of the essence.

PMID- 21851175
TI  - Genetic variations in the interleukin-6 and interleukin-8 genes and the
      interleukin-6 receptor gene in delirium.
AB  - OBJECTIVE: The aim of this study was to investigate whether genetic polymorphisms
      in the interleukin-6 gene (IL6), the IL-6 receptor gene (IL6R), and the IL-8 gene
      (IL8) were associated with delirium in a population of acutely admitted older
      patients. METHODS: This was a prospective cohort study in the Academic Medical
      Center in Amsterdam, running from April, 2003, through August, 2008. A total of
      881 patients, aged 65 years and older, acutely admitted to the medical department
      or to the surgical department following hip fracture, were included in the study.
      Delirium was diagnosed by the Confusion Assessment Method. Two single-nucleotide
      polymorphisms (SNPs) in the IL6 gene, one in the IL6R gene, and one in the IL8
      gene were genotyped. RESULTS: Fifty percent of the 115 surgical patients and 34%
      of the 605 medical patients experienced delirium. Delirious patients were older
      (82.8 years vs. 77.6 years) and had more frequent pre-existing functional (64%
      vs. 36%) or cognitive impairment (83% vs. 26%) (p < 0.001). The determination of
      polymorphisms had success rates between 87% and 96%. Rs1800697 and rs1800797 in
      the IL6 gene, rs8192284 in the IL6R gene, and rs4073 in the IL8 gene were not
      associated with the development of delirium. CONCLUSION: Recent observations have
      indicated that IL-6 and IL-8 play a role in delirium in the elderly, but
      functional genetic variations in the IL6, IL6R, and IL8 genes were not associated
      with delirium. Still, the inflammatory hypothesis of delirium is gaining ground
      in the literature on the basis of recent animal research.

PMID- 21851176
TI  - Rapamycin as an antiaging therapeutic?: targeting mammalian target of rapamycin
      to treat Hutchinson-Gilford progeria and neurodegenerative diseases.
AB  - Mammalian target of rapamycin (mTOR), a serine/threonine kinase and component of
      the mTORC1 signaling complex, acts as an energy, nutrient, growth factor, stress,
      and redox sensor to increase protein synthesis and decrease macroautophagy.
      mTORC1 plays a central role in the maintenance of homeostasis and its
      deterioration, seen in aging. The Food and Drug Administration (FDA)-approved
      immunosuppressive macrolide rapamycin binds immunophilin FKBP12 (FK506-binding
      protein) to inhibit mTORC1. Unlike most other interventions tested to date,
      inhibition of mTORC1 by rapamycin extends life span in old mice, likely by a
      combination of increased autophagy and decreased mRNA translation. Hutchinson
      Gilford progeria syndrome (HGPS) is a lethal genetic disorder affecting children
      that is characterized by symptoms of premature aging, such as atherosclerosis.
      Increased autophagy induced by rapamycin reduces accumulation of progerin, an
      alternate spliced form of lamin A/C, that forms insoluble toxic aggregates,
      resulting in reduced HGPS-associated nuclear blebbing, growth inhibition,
      epigenetic dysregulation, and genomic instability. Rapamycin-induced autophagy
      also suppresses symptoms in mouse models of Alzheimer, Parkinson, and Huntington
      diseases, where toxic insoluble protein aggregates accumulate. On the basis of
      these results, modulation of mTORC1 function is a promising target for the
      development of therapeutics for neurodegenerative diseases and HGPS. Rapamycin is
      the obvious candidate for near-term evaluation in the treatment of these
      diseases. However, the substantial set of rapamycin-associated adverse effects,
      as well as the lack of aging-specific human data, should caution the routine use
      of rapamycin as an antiaging agent. The use of safer, but perhaps weaker,
      indirect mTORC1 inhibitors, such as metformin and resveratrol, may prove useful.
      Further study will ascertain whether such compounds extend human health or life
      span.

PMID- 21851178
TI  - Meeting report: American Aging Association 40th Annual Meeting, Raleigh, North
      Carolina, June 3-6, 2011.
AB  - The focus of the 2011 American Aging Association meeting was emerging concepts in
      the mechanisms of aging. Many of the usual topics in aging were covered, such as
      dietary restriction (DR), inflammation, stress resistance, homeostasis and
      proteasome activity, sarcopenia, and neural degeneration. There was also
      discussion of newer methods, such as microRNAs and genome sequencing, that have
      been employed to investigate gene expression variance with aging and genetic
      signatures of longevity. Aging as a field continues to mature, including the
      following areas: Using a systems approach to tracing conserved pathways across
      organisms; sharpening definitions of sarcopenia, frailty, and health span; and
      distinguishing interventions by age tier (early-onset versus late-onset). A
      preconference session on late-onset intervention concluded that there are
      numerous benefits to deriving such interventions. Conference talks applied the
      biology of aging in a translational manner to intervention development. Using an
      individual's own stem cells to regenerate organs for transplantation and as a
      cell source for cellular therapies could be a powerful near-term solution to
      disease. Several proposed interventions were pharmaceutical, myostatin
      inhibition, losartan, Janus kinase (JAK) pathway inhibitors, and enalapril for
      frailty and sarcopenia, and metformin to promote the Nrf2 antiinflammation
      response. In DR, protein restriction was found to be better than general calorie
      restriction. Short-term fasting may be helpful in chemotherapy, surgery, and
      acute stress, simultaneously increasing the killing of cancer cells by
      chemotherapy, while improving the survival of normal cells. Immune system
      interventions remain elusive, although statins may help to improve cellular
      senescence promoted bacterial infection. Engineered enzymes may be useful in
      lysosomal catabolism. Dietary restriction mimetics, most promisingly involving
      target of rapamycin (TOR; TORC1 inhibition and rapamycin), may be more feasible
      than dietary restriction.

PMID- 21851179
TI  - Personal profile: interview with Bill Andrews, Ph.D.
AB  - Dr. William H. Andrews has worked in the biotech industry for 31 years, focusing
      the last 19 years on finding ways to extend human life span through the
      intervention of telomere shortening in human cells. Dr. Andrews earned his Ph.D.
      in Molecular and Population Genetics at the University of Georgia. He was a
      Senior Scientist at Armos Corporation and Codon Corporation, Director of
      Molecular Biology at Codon and at Geron Corporation, and Director of Technology
      Development at EOS Biosciences. He is presently the founder, President, and CEO
      of Sierra Sciences, a biotechnology company focused exclusively on finding drugs
      that will transiently induce the expression of endogenous telomerase in human
      cells. Sierra Sciences has already identified more than 30 such drugs and is
      presently characterizing their mechanism of action. While Director of Molecular
      Biology at Geron Corporation, Dr. Andrews was one of the principal discoverers of
      both the RNA and protein components of human telomerase and was awarded second
      place as "National Inventor of the Year" in 1997 for this work. He is presently a
      named inventor on 43 U.S- issued telomerase patents.

PMID- 21851181
TI  - Transient middle cerebral artery occlusion and reperfusion alters inducible NOS
      expression within the ventrolateral medulla and modulates cardiovascular function
      during static exercise.
AB  - A major cause of stroke is cerebral ischemia in regions supplied by the middle
      cerebral artery (MCA). In this study, we hypothesized that compromised
      cardiovascular function during static exercise may involve altered expression of
      inducible NOS (iNOS) protein within the rostral ventrolateral medulla (RVLM) and
      caudal ventrolateral medulla (CVLM). We compared cardiovascular responses and
      iNOS protein expression within the left and right sides of both RVLM and CVLM in
      sham-operated rats and in rats with a 90 min left-sided MCA occlusion (MCAO)
      followed by 24 h of reperfusion. Increases in blood pressure during a static
      muscle contraction were attenuated in MCAO rats compared with sham-operated rats.
      Also, iNOS expression within the left RVLM was augmented compared with the right
      RVLM in MCAO rats and compared with both RVLM quadrants in sham-operated rats. In
      contrast, compared with sham-operated rats and the right CVLM of MCAO rats, iNOS
      expression was attenuated in the left CVLM in left-sided MCAO rats. These data
      suggest that the attenuation of pressor responses during static exercise in MCAO
      rats involves overexpression of iNOS within the ipsilateral RVLM and attenuation
      in iNOS within the ipsilateral CVLM. Differential expression of iNOS within the
      medulla plays a role in mediating cardiovascular responses during static exercise
      following stroke.

PMID- 21851182
TI  - Low-income, ethnically diverse consumers' perspective on health information
      exchange and personal health records.
AB  - We surveyed low-income, ethnically diverse consumers regarding their attitudes
      towards providers' use of electronic health information exchange (HIE) and
      consumer use of HIE through personal health records (PHRs). Amongst respondents
      (n=214), 48% had an annual household income below $15,000 and 62% spoke a
      language other than English at home. A majority indicated that they supported
      providers' use of HIE (61%). Support for providers' use of HIE was independently
      associated with consumer willingness to permit health care providers other than
      their primary care doctor to view their electronic medical record information
      (odds ratio (OR)=2.92, 95% confidence interval (CI)=1.31-6.50) and beliefs that
      electronic health record use would improve quality of care (OR=2.70, 95% CI=1.18
      6.18). Seventy-eight percent would potentially use PHRs. Potential PHR use was
      independently associated with Internet usage rates, (OR=4.46, 95% CI=1.77-11.22),
      belief that PHR use would improve their understanding of their own healthcare
      (OR=3.12, 95% CI=1.27-7.67) and comfort with sharing PHR data with their primary
      care doctor (OR=2.79, 95% CI=1.09-7.11). Low-income, ethnically diverse consumers
      affected by interoperable health information technology (IT) initiatives largely
      support using PHRs and HIE, provided these systems demonstrate benefits and
      address the privacy and security of their electronic health information. Although
      we found interest in PHRs comparable or higher than nationally representative
      populations, support for HIE was lower, and thus efforts will need to be made to
      engage low-income and ethnically diverse consumers to participate in
      interoperable health IT initiatives.

PMID- 21851184
TI  - Response to Lammers and Witjes article: new developments in intravesical therapy
      for non-muscle-invasive bladder cancer.

PMID- 21851183
TI  - Low-level laser light therapy improves cognitive deficits and inhibits microglial
      activation after controlled cortical impact in mice.
AB  - Low-level laser light therapy (LLLT) exerts beneficial effects on motor and
      histopathological outcomes after experimental traumatic brain injury (TBI), and
      coherent near-infrared light has been reported to improve cognitive function in
      patients with chronic TBI. However, the effects of LLLT on cognitive recovery in
      experimental TBI are unknown. We hypothesized that LLLT administered after
      controlled cortical impact (CCI) would improve post-injury Morris water maze
      (MWM) performance. Low-level laser light (800 nm) was applied directly to the
      contused parenchyma or transcranially in mice beginning 60-80 min after CCI.
      Injured mice treated with 60 J/cm2 (500 mW/cm2*2 min) either transcranially or
      via an open craniotomy had modestly improved latency to the hidden platform
      (p<0.05 for group), and probe trial performance (p<0.01) compared to non-treated
      controls. The beneficial effects of LLLT in open craniotomy mice were associated
      with reduced microgliosis at 48 h (21.8+/-2.3 versus 39.2+/-4.2 IbA-1+
      cells/200*field, p<0.05). Little or no effect of LLLT on post-injury cognitive
      function was observed using the other doses, a 4-h administration time point and
      7-day administration of 60 J/cm2. No effect of LLLT (60 J/cm2 open craniotomy)
      was observed on post-injury motor function (days 1-7), brain edema (24 h),
      nitrosative stress (24 h), or lesion volume (14 days). Although further dose
      optimization and mechanism studies are needed, the data suggest that LLLT might
      be a therapeutic option to improve cognitive recovery and limit inflammation
      after TBI.

PMID- 21851185
TI  - Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant
      treatment of locally advanced rectal cancer: results of a phase II study.
AB  - BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus
      oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant
      treatment of locally advanced rectal cancer patients, was shown feasible in our
      previous study. The aim of this study was to evaluate the efficacy in terms of
      pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A
      Phase II study was designed and clinical stage T3-T4 and/ or N >= 1 patients were
      treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent
      chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in
      terms of clinical and pathologic response to pre-operative therapy. According to
      the Gehan's design study, 25 patients were enrolled. Toxicity was assessed
      according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five
      consecutive patients were treated. Twenty-two of the 25 (88%) patients had a
      partial clinical response at the time of pre-operative magnetic resonance imaging
      (MRI). Only one patient showed progressive systemic disease at pre-surgical
      revaluation and was subjected only to biopsy to evaluate pathological response.
      Twenty-four patients (96%) underwent surgery. Overall, pathologic complete
      response was observed in eight patients (32%; CI 0.95:12-55%) and only
      microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%).
      Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were
      the most frequent acute side effects experienced. Eighteen patients had grade 1-2
      toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year
      Local control and actuarial Disease Free Survival were 100% and 91%,
      respectively. CONCLUSION. An intensified regimen of concomitant boost
      radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely
      administered in patients with locally advanced rectal cancer. This regimen
      produces high rates of pathological complete response. Based on available data,
      this type of treatment could be offered to patients with more advanced tumors (T4
      or local recurrence).

PMID- 21851186
TI  - Testicular-cancer survivors experience compromised language following
      chemotherapy: findings in a Swedish population-based study 3-26 years after
      treatment.
AB  - BACKGROUND: Studies suggest an increased risk for compromised cognitive function
      among cancer survivors. It is unclear to what extent chemotherapy is the cause
      and how the dysfunction, when present, affects everyday life. The objective was
      to study self-reported behaviours that may depend on cognitive function, among
      testicular-cancer survivors who received various cycles of cisplatin-based
      chemotherapy by comparing them with those who did not. MATERIAL AND METHODS: We
      identified 1173 eligible men diagnosed with non-seminomatous testicular cancer
      treated according to the national cancer-care programs SWENOTECA I-IV between
      1981 and 2004. During an 18-month qualitative phase we constructed a study
      specific questionnaire including questions about specific activities and
      behaviour in everyday life. RESULTS: We obtained information from 960 of 1173
      (82%) testicular-cancer survivors diagnosed on average 11 years previously. The
      prevalence of "saying similar but incorrect words" at least once a week was 5%
      among those having received no chemotherapy versus 16% among those having
      received five or more cycles, giving a prevalence ratio ("relative risk", RR) of
      3.3 with a 95% confidence interval of 1.5 to 7.1. The corresponding figure for
      "saying words in the wrong order" was 3.1 (1.7-5.8), for "difficulties
      understanding what other people mean" 3.1 (1.3-7.7), for "saying words other than
      planned" 2.2 (1.1-4.5) and for "difficulties completing sentences" 2.0 (1.0-3.6).
      The relative risks for those with a low level of education ranged between 4.9
      (1.6-14.9) and 15.3 (1.9-120.5). CONCLUSION: Testicular-cancer survivors in
      Sweden who have received five or more cycles of cisplatin-based chemotherapy
      experience an increased incidence of long-term compromised language; the effect
      is primarily seen among men with a low level of education.

PMID- 21851187
TI  - FDG PET/CT differentiating two malignant tumors in the same patient.

PMID- 21851188
TI  - Age-grouped differences in adverse drug events from psychotropic medication.
AB  - OBJECTIVE: This review aims to detail specific psychotropic medication treatment
      differences in adverse drug events (ADEs) between children, adolescents, and
      adults. METHOD: A thorough data-based search of ADEs was made, augmented by
      findings from approved and updated U.S. Food and Drug Administration (FDA) drug
      labels, controlled clinical trial reports, and from FDA information on ADEs at
      scheduled public hearings. RESULTS: Children were found to generally exhibit more
      ADEs to psychotropic medication than adolescents and adults. These ADEs primarily
      include altered growth velocity, rash, vomiting, dystonia, tics, affect lability,
      activation, metabolic blood test abnormalities, sedation, sialorrhea, and
      electrocardiogram irregularities. CONCLUSION: Children have more biological
      vulnerabilities than older individuals, which could account for their greater
      rate of ADEs to psychotropic medication treatment.

PMID- 21851190
TI  - Preschool onset attention-deficit/hyperactivity disorder: course and predictors
      of stability over 24 months.
AB  - OBJECTIVE: The present study examined the course of ADHD over 24 months in a
      preschool population. METHOD: n=48 preschoolers with ADHD, aged 3.0-5.11 years,
      subjects included in a larger sample of preschoolers with depression and other
      disorders (n=306) were comprehensively assessed at 3 annual time points over 24
      months in a prospective longitudinal follow-up study. RESULTS: Baseline diagnoses
      of preschool MDD, ODD, and CD were risk factors for ADHD diagnosis over 24 months
      in this preschool population. Among older preschoolers and after controlling for
      key demographic variables, ADHD predicted later ADHD diagnosis, along with other
      significant risk factors - baseline diagnosis of ODD, and/or family history of
      disruptive disorders, and stressful life events. CONCLUSIONS: ADHD showed greater
      homotypic continuity at later rather than earlier preschool ages. Other
      disruptive comorbidities also emerged as key predictors of stable ADHD course.
      Study findings may help to inform which preschool ADHD populations to target for
      early intervention. Larger sample sizes are needed to confirm these findings and
      to further explore the stability, course, and predictors of outcome of preschool
      onset ADHD.

PMID- 21851191
TI  - Platelet vesicular monoamine transporter 2 density in the disruptive behavior
      disorders.
AB  - In a former study, we reported decreased platelet vesicular monoamine transporter
      2 (VMAT2) density (Bmax) in patients with ADHD. The current study aimed at
      measuring platelet VMAT2 in the disruptive behavior disorders (DBDs) to assess
      whether this finding is specific to ADHD or generalizable to the broader DBD
      concept. The study included 13 patients with DBDs aged 10-12 years and 16 healthy
      volunteers aged 8-17 years. All participants underwent a thorough clinical
      evaluation using Schedule for Affective Disorders and Schizophrenia for School
      Age Children-Present and Lifetime version for diagnosis, the Nisonger Child
      Behavior Rating Form, the Clinical Global Impressions Scale-Severity version, and
      the DSM-IV ADHD Scale (DAS). The study group's DAS scores did not differ from
      those of the control group. There was no significant difference between the
      patients with DBDs and the control group either in VMAT2 density (Bmax) or
      affinity (Kd) as measured by high-affinity [(3)H]TBZOH binding. We conclude that
      the formerly reported decreased platelet VMAT2 Bmax in patients with ADHD may be
      specific to ADHD and not present in DBDs. Larger-scale replication is needed.

PMID- 21851189
TI  - Clinical characteristics of children receiving antipsychotic medication.
AB  - This study explored the demographic and diagnostic features of children who were
      currently receiving antipsychotics compared to children who were receiving other
      psychotropics in a cohort of children with and without elevated symptoms of mania
      (ESM). Participants were recruited from 10 child outpatient mental health clinics
      associated with four universities. Guardians with children between 6-12 years who
      presented for new clinical evaluations completed the Parent General Behavior
      Inventory-10 Item Mania Scale (PGBI-10M). All children who scored >=12 on the
      PGBI-10M and a select demographically matched comparison group of patients who
      scored <=11 were invited to participate. Children were divided into two groups:
      those receiving at least one antipsychotic medication and those receiving other
      psychotropic medications. The groups were compared on demographics, diagnoses,
      psychiatric symptoms, functioning, and past hospitalizations. Of the 707 children
      enrolled in the Longitudinal Assessment of Manic Symptoms (LAMS) study, 443 (63%)
      were prescribed psychotropic medication at baseline: 157 (35%) were receiving an
      antipsychotic and 286 (65%) were prescribed other agents. Multivariate results
      indicated that being prescribed antipsychotics was related to being white,
      previous hospitalization, having a psychotic or bipolar 1 disorder and the site
      where the child was receiving services (p<0.001). In this sample, it is
      relatively common for a child to be prescribed an antipsychotic medication.
      However, the only diagnoses associated with a greater likelihood of being treated
      with an antipsychotic were psychotic disorders or unmodified DSM-IV bipolar 1
      disorder.

PMID- 21851192
TI  - An open label trial of donepezil for enhancement of rapid eye movement sleep in
      young children with autism spectrum disorders.
AB  - BACKGROUND: Rapid eye movement (REM) sleep is greatest in the developing brain,
      is driven by acetylcholine, and may represent a protected time for
      neuroplasticity. Recently published data from our lab observed that children with
      autism spent significantly less time in this state during a single night
      recording than did typically developing children and those with developmental
      delay without autism. The objective of this study was to determine whether or not
      donepezil can increase the REM % in children with diagnosed autism spectrum
      disorder (ASD) found to have REM % values of at least two standard deviations
      below expected for age. METHODS: Five subjects found to have an ASD (ages 2.5-6.9
      years) and demonstrated deficits in REM sleep compared with within-lab controls
      were enrolled in a dose finding study of donepezil. Each subject was examined by
      polysomnography for REM sleep augmentation after drug administration. RESULTS:
      REM sleep as a percentage of Total Sleep Time was increased significantly and REM
      latency was decreased significantly after drug administration in all subjects. No
      other observed sleep parameter was changed significantly. CONCLUSIONS: Donepezil
      can increase the amount of time that children with an ASD spend in the REM sleep
      state. A double-blind, placebo-controlled trial is needed to assess the
      association between REM sleep augmentation and learning, cognition, and behavior
      in such children.

PMID- 21851194
TI  - Dysphoria associated with neuroleptic withdrawal in an adolescent with Tourette's
      disorder.

PMID- 21851195
TI  - Effects of D-cycloserine on craving to alcohol cues in problem drinkers:
      preliminary findings.
AB  - BACKGROUND: It has been shown that the partial N-methyl-d-aspartate (NMDA)
      agonist d-cycloserine (DCS) facilitates exposure-based learning in humans with
      anxiety disorders. However, the effects of DCS on exposure to substance cues are
      still uncertain. OBJECTIVE: The primary aim of the study was to examine the
      effects of DCS on exposure sessions to alcohol cues. METHODS: Twenty non
      treatment-seeking problem drinkers were randomly assigned to receive 50 mg of DCS
      or placebo 50 minutes prior to each of 3 alcohol cue exposure sessions consisting
      of 5 exposure trials within an 8-day period. Following this, participants
      underwent two test sessions without the administration of any medication. The
      test sessions occurred 3 and 7 days after the last cue exposure session,
      respectively. Dependent measures included drinking urge and heart rate and
      drinking urge during the test sessions. RESULTS: Individuals who received DCS
      showed increased craving to alcohol cues as compared with individuals who
      received placebo during the first test session. No group difference in drinking
      urge was found during the second test session. Furthermore, the groups did not
      differ in heart rate at any of the assessment points. CONCLUSIONS: The results
      suggest that DCS may temporarily augment cue-elicited craving for alcohol.
      SCIENTIFIC SIGNIFICANCE: As in an earlier study with cocaine-dependent
      individuals, DCS appears to exhibit a different profile in problem drinkers to
      those with anxiety disorders. Dose, timing, arousal, and treatment motivation as
      considerations are discussed, as are methodological considerations and the need
      for additional studies in this area.

PMID- 21851196
TI  - Clinical pictures and novel mutations of WT1-associated Denys-Drash syndrome in
      two Chinese children.
AB  - Denys-Drash syndrome (DDS) is characterized by early onset of nephropathy,
      genitalia malformation, and Wilms' tumor, where WT1 is the gene that is mutated
      in most patients. We report two de novo mutations in WT1 found in two Chinese DDS
      children. Patient 1 was a boy with complete DDS who was presented with
      progressive nephropathy, unilateral Wilms' tumor, bilateral cryptorchidism, and
      renal histology showing diffuse mesangial sclerosis (DMS). When the patient was
      24 months old, a liver ultrasound showed multiple nodules, and the patient died
      of pneumonia 1 month later. The de novo novel mutation, c.1130A>T (p.His377Leu),
      was identified; the mutation replaces histidine with leucine in the zinc finger
      (Znf) structure and is predicted to change the local spatial structure of the
      protein. Patient 2 had 46 XX with incomplete DDS and presented with normal
      genitalia, proteinuria, unilateral Wilms' tumor with renal pedicle lymph node
      metastasis, and renal histology showing DMS. Her renal function remains normal
      after 48 months. A de novo mutation, c.1168C>T (p.Arg390Term), was identified; it
      truncates 60 amino acids at the C terminus, and it is predicted to result in loss
      of the DNA-binding capacities of the WT1 protein.

PMID- 21851197
TI  - Implication of CKD-EPI equation to estimate glomerular filtration rate in Chinese
      patients with chronic kidney disease.
AB  - OBJECTIVE: To evaluate the applicability of the Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration
      rate (GFR) in Chinese patients of different stages of CKD. METHODS: The CKD-EPI
      equation estimated GFR (eGFR) was compared with body surface area standardized
      GFR (sGFR), which was measured by diethylenetriaminepentaacetic acid renal
      dynamic imaging method in 142 CKD cases. RESULTS: eGFR was positively correlated
      with sGFR (r = 0.838, p < 0.001). eGFR of 15%, 30%, and 50% accuracy were 31.0%,
      57.7%, and 76.8%, respectively. Average deviation of eGFR from sGFR was -0.92 +/-
      16.36 mL/min/1.73 m2 (p = 0.506). There was no significant deviation in the CKD
      from stages 2 to 5. However, in CKD stage 1, the deviation was increased with the
      value of 13.36 +/- 18.44 mL/min/1.73 m(2) (p = 0.023). CONCLUSION: CKD-EPI
      equation might be widely used in evaluation of Chinese CKD patients of different
      stages, with a less deviation and higher accuracy. However, in CKD stage 1, eGFR
      was higher than sGFR on average. It was suggested that eGFR might be
      overcorrected or overestimated. These results demonstrated that careful
      modification of CKD-EPI equation would be necessary in Chinese populations with
      CKD.

PMID- 21851198
TI  - The relationship between tumor necrosis factor-alpha polymorphisms and hepatitis
      C virus infection: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV) is now recognized as one of the
      major causes of chronic liver disease. It is also one of the most common
      complications in maintenance hemodialysis (HD) patients. Tumor necrosis factor
      (TNF)-alpha promoter polymorphisms are observed to modulate TNF-alpha levels and
      thought to have an effect on susceptibility to HCV infection and the virus
      clearance, but the results are inconsistent. In this study, a systematic review
      and meta-analysis of the published data was performed to evaluate the
      relationship between the TNF-alpha-238, -308 polymorphisms and HCV infection.
      METHODS: A total of 15 studies published were analyzed, which were indexed from
      PubMed, Embase, and CNKI databases (up to December 2010). All the data were
      analyzed using RevMan 4.2 software. Odds ratios (OR) and confidence intervals
      (95% CI) were calculated by fixed or random-effects models. Heterogeneity and
      publication bias across the studies were also explored. RESULTS: The data showed
      no significant association between TNF-alpha-308, -238 gene polymorphisms and the
      susceptibility to HCV infection in the global group (p = 0.28, p = 0.38,
      respectively) and the sub-groups (European, American, African, and Asian).
      Besides, the distributions of TNF-alpha-308, -238 A/G alleles were also not
      significantly different between the persistent infection group and the
      spontaneous clearance group (p = 0.64, p = 0.75, respectively). CONCLUSION: TNF
      alpha-238, -308 gene polymorphisms might have no effect on susceptibility to HCV
      infection and the virus clearance. The findings of this meta-analysis have
      implications in the optimal prevention of HCV in HD patients and in the guidance
      of future research.

PMID- 21851199
TI  - Association between ABCB1 (MDR1) gene 3435 C>T polymorphism and colchicine
      unresponsiveness of FMF patients.
AB  - The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette
      transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial
      role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype
      of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and
      effluxes many chemically diverse compounds across the plasma membrane. We studied
      the association between C3435T polymorphisms (single nucleotide polymorphism) of
      MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients.
      Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness
      were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were
      genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The
      preliminary current results showed increased T allele frequency (0.596) in
      colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and
      TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%,
      respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1
      gene is associated with colchicine resistance in nonresponder FMF patients during
      the common therapy protocol.

PMID- 21851200
TI  - Factors related to recent alcohol abstinence among individuals who received
      previous treatment.
AB  - BACKGROUND: Alcohol problems are widespread throughout the United States. While
      treatment can be successful, many individuals continue to drink. One method to
      assess treatment results over time is by investigating abstinence as a measure of
      success. OBJECTIVES: The main aim of this study is to investigate factors that
      may be associated with past-year (PY) abstinence among individuals who received
      prior-to-past-year (PPY) treatment for alcohol problems, while also assessing
      abstinence by treatment subtype. METHOD: This study uses data from 1742
      individuals who received PPY treatment for alcohol problems in the 2001-2002
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
      Logistic regression models were used to assess the strength of association
      between alcohol abstinence and key demographic and clinical factors. RESULTS: The
      level of PY abstinence was 36.5% among those who previously sought treatment for
      alcohol problems. Younger age groups and those who were nicotine dependent or had
      a cannabis use disorder were less likely to be abstinent. There were no
      differences based on sex or PY major depression or generalized anxiety disorder.
      CONCLUSION: While causal inferences cannot be made, these results suggest that
      the majority of people continue to drink, even after being treated for alcohol
      problems. Nonetheless, variation may exist depending on the form of treatment a
      person receives. More research is needed regarding long-term levels of abstinence
      after individuals receive treatment.

PMID- 21851201
TI  - Parental prescription opioid abuse and the impact on children.
AB  - OBJECTIVE: The purpose of this study was to identify which characteristics of
      opioid-abusing parents were associated with greater global impairment of their
      children. METHODS: Data regarding participant demographics, drug use, and child
      demographics were collected from 14 patients in a chemical dependency unit who
      had at least one child between the ages of 4 and 17, inclusive. Child global
      impairment was measured by the parents' report using the Brief Impairment Scale
      (BIS). Regression analyses were conducted to assess which parental
      characteristics were associated with child BIS scores. RESULTS: The mean age of
      the 14 participants was approximately 40 years, 9 (64.3%) were women, and 12
      (85.7%) were white. At the time of hospitalization, 12 (85.7%) had had prior
      substance abuse treatment, 9 (64.3%) had received prescription opioids through
      non-medical sources, and 9 (64.3%) had a criminal history. The mean BIS score of
      24 children was 15.5, which is associated with moderate global impairment of
      function. Greater child BIS scores were associated with a number of parental
      characteristics, such as obtaining any prescription opioids through non-medical
      sources, having a greater number of arrests, previously using drugs
      intravenously, and having a greater number of prior substance abuse treatment
      episodes. CONCLUSIONS: By assessing these parental characteristics, clinicians
      may be able to assess children who are at risk for impairment and, in turn, may
      be in need of mental health services. Due to limitations of this study, further
      evaluation is needed.

PMID- 21851202
TI  - Utilizing peer mentorship to engage high recidivism substance-abusing patients in
      treatment.
AB  - BACKGROUND: Often high recidivism substance-using patients have difficulty
      connecting to outpatient treatment contributing to greater functioning
      disturbances. Approaches to address this problem frequently are staff extensive.
      OBJECTIVE: This study evaluates the impact of peer mentorship and/or enhanced
      dual recovery treatment (DRT) on individuals who are inpatients, substance
      abusing, and have a history of high recidivism. The primary outcome is post
      discharge treatment attendance. METHODS: In an inpatient Veterans Administration
      hospital setting, 96 patients with a history of high recidivism and current
      and/or past diagnosis of substance use disorders were randomized to either (i)
      Treatment As Usual (TAU), (ii) TAU + DRT + Mentorship for Addictions Problems to
      Enhance Engagement to Treatment (MAP-Engage), or (iii) TAU + MAP-Engage. RESULTS:
      Overall MAP-Engage was found to be comparable to the DRT + MAP-Engage and both of
      these conditions were significantly better than TAU alone at increasing adherence
      to post-discharge substance abuse, medical, and mental health outpatient
      appointments. CONCLUSION/SCIENTIFIC SIGNIFICANCE: MAP-Engage offers an
      alternative approach to address lack of attendance to outpatient treatment
      appointments post discharge that is relatively low in staff reliance.

PMID- 21851203
TI  - A comparison of cognitive function in patients under maintenance treatment with
      heroin, methadone, or buprenorphine and healthy controls: an open pilot study.
AB  - INTRODUCTION: Cognitive impairment has been reported in drug-dependent patients
      under opioid maintenance treatment. OBJECTIVES: To compare cognitive functioning
      in healthy controls and in opioid-dependent patients treated with Buprenorphine,
      Heroin, or methadone maintenance. METHODS: We used the standardized test battery
      ART-90 to study cognitive function in patients under long-term heroin treatment
      (n = 20), Bup (n = 22), or Met (n = 24) maintenance treatment and healthy
      controls (n = 25). RESULTS: Patients receiving heroin performed significantly
      worse than healthy controls in most domains. Heroin patients performed worse than
      patients in the other two treatment groups in subtests measuring psychomotor
      performance under stress conditions and monotony. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: Although a number of limitations must be taken into account, this
      study provides some preliminary evidence that cognitive function may be more
      impaired in patients under heroin maintenance treatment than in patients
      receiving Bup or Met and in healthy controls.

PMID- 21851204
TI  - Long-term effect of nutritional counselling on desired gain in body mass and lean
      body mass in elite athletes.
AB  - Lean body mass (LBM) is important in power-related sports. In athletes with heavy
      training loads and competitions, it may be difficult to increase and maintain LBM
      during the season. The purpose of this study was to evaluate the long-term
      effects on body composition after an 8-12 week weight-gain period with or without
      nutritional guidance. Twenty-one elite athletes where randomized to 1 of 2
      groups: the nutritional counselling group (NCG; n = 12, 18.5 +/- 1.7 y, 67.8 +/-
      7.4 kg) and the ad libitum group (ALG; n = 9, 19.6 +/- 2.7 y, 74.2 +/- 5.7 kg).
      The NCG followed a meal plan that provided a surplus of 506 +/- 84 kcal.day(-1),
      whereas the ALG had an ad libitum energy intake (EI) during the strength-training
      (4 sessions per week) intervention. Body mass (BM) and body composition were
      measured pre- and postintervention, and 6 and 12 months after the intervention.
      EI in the NCG was normalized after 12 months, whereas EI in the ALG was unchanged
      during or after the intervention. BM increased more in the NCG than in the ALG
      during the intervention (4.3% +/- 0.9% vs. 1.0% +/- 0.6%) and after 12 months
      (6.0% +/- 0.9% vs. 1.8% +/- 0.7%). LBM increased in the NCG during the
      intervention (2.8% +/- 0.5%) and after 12 months (4.4% +/- 1.0%), whereas LBM in
      the ALG was unchanged. The NCG managed to maintain and increase BM and LBM after
      the intervention period. Hence, the focus on nutritional guidance, in addition to
      strength training, seems to be preferable for obtaining the long-term effect of
      weight gain in athletes.

PMID- 21851205
TI  - Family meals and body mass index among adolescents: effects of gender.
AB  - Family meals have been identified as a protective factor against obesity among
      youth. However, gender specificities with respect to the relationship between the
      frequency of family meals and body mass index (BMI) have not been investigated.
      The purpose of this study was to examine the relationship between the frequency
      of family meals and BMI in male and female adolescents, while controlling for
      potential confounding factors associated with BMI, such as parental education,
      adolescent's age, and snack-food eating. Research participants were 734 male and
      1030 female students (mean age, 14.12 years, SD = 1.62) recruited from middle
      schools and high schools in the capital region of Canada. Participants completed
      validated, self-report measures to assess the frequency of family meals and the
      risk factors associated with increased BMI, which was derived from objective
      measures of height and weight. After controlling for proposed confounding
      variables, a higher frequency of family meals was associated with lower BMI in
      females, but not in males. A Z-transformation test of the homogeneity of adjusted
      correlation coefficients showed a significant trend (p = 0.06), indicating that
      the relationship between family meals and BMI is stronger in females than males,
      consistent with our regression analyses. Our findings suggest that eating
      together as a family may be a protective factor against obesity in female
      adolescents, but not in male adolescents. Findings from this study have important
      implications for parents and health care practitioners advocating for more
      frequent family meals as part of a comprehensive obesity prevention and treatment
      program for female adolescents.

PMID- 21851206
TI  - Tumor growth reduction in Walker 256 tumor-bearing rats performing anaerobic
      exercise: participation of Bcl-2, Bax, apoptosis, and peroxidation.
AB  - Physical activity has been used in cancer prevention and treatment. In this
      study, we investigated some of the mechanisms by which anaerobic exercise reduces
      tumor growth. To do so, rats were trained for 8 weeks. Training consisted of
      jumping in a swimming pool for ten 30-s sets, with a load that was 50% of body
      weight attached to the back, 4 times per week. At the sixth week, anaerobic
      exercise trained rats (EX group) were inoculated with a suspension of Walker 256
      tumor cells. Tumor weight, apoptotic tumor cells, tumor Bax and Bcl-2 protein
      expression, tumor lipid peroxidation, and tumor cell proliferation ex vivo were
      evaluated. Tumor weight was significantly lower in the EX group (~30%) than in
      rats that did not undergo training (sedentary group) (p < 0.05). Apoptosis in the
      tumor cells of EX rats was 2-fold higher than in the tumor cells of sedentary
      rats; in addition, Bax expression increased by 10% and Bcl-2 decreased by 13% in
      EX rats. Lipid peroxidation was 4-fold higher in the tumor cells of EX rats than
      in those of sedentary rats (p < 0.05). Tumor cell proliferation ex vivo was 29%
      lower in the EX group than in the sedentary group (p < 0.05). In conclusion,
      Walker 256 tumor-bearing exercised rats presented more tumor cell apoptosis, a
      higher tumor content of lipid peroxides, pro-apoptotic protein expression
      balance, and reduced tumor weight and cell proliferation ex vivo, compared with
      sedentary rats. These events, together, account for the lower tumor growth we
      observed in the EX rats.

PMID- 21851207
TI  - Characteristics of rural crack and powder cocaine use: gender and other
      correlates.
AB  - BACKGROUND: Little is known about the relationship of gender with cocaine use in
      rural areas. This study describes these relationships among stimulant users
      residing in rural areas of Arkansas, Kentucky, and Ohio. OBJECTIVES:
      Understanding the characteristics of crack and powder cocaine users in rural
      areas may help inform prevention, education, and treatment efforts to address
      rural stimulant use. METHODS: Participants were 690 stimulant users, including
      274 (38.6%) females, residing in nine rural counties. Cocaine use was measured by
      self-report of cocaine use, frequency of use, age of first use, and cocaine
      abuse/dependence. Powder cocaine use was reported by 49% of this sample of
      stimulant users and 59% reported using crack cocaine. FINDINGS: Differing use
      patterns emerged for female and male cocaine users in this rural sample; females
      began using alcohol, marijuana, and cocaine at later ages than males but there
      were no gender differences in current powder cocaine use. Females reported more
      frequent use of crack cocaine and more cocaine abuse/dependence than males, and
      in regression analyses, female crack cocaine users had 1.8 times greater odds of
      reporting frequent crack use than male crack users. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: These findings suggest differing profiles and patterns of cocaine
      use for male and female users in rural areas, supporting previous findings in
      urban areas of gender-based vulnerability to negative consequences of cocaine
      use. Further research on cocaine use in rural areas can provide insights into
      gender differences that can inform development and refinement of effective
      interventions in rural communities.

PMID- 21851209
TI  - Pharmacophore generation and atom-based 3D-QSAR of novel quinoline-3-carbonitrile
      derivatives as Tpl2 kinase inhibitors.
AB  - Tumour progression locus-2 (Tpl2) is a serine/threonine kinase, which regulates
      the expression of tumour necrosis factor alpha. The article describes the
      development of a robust pharmacophore model and the investigation of structure
      activity relationship analysis of quinoline-3-carbonitrile derivatives reported
      for Tpl2 kinase inhibition. A five point pharmacophore model (ADRRR) was
      developed and used to derive a predictive atom-based 3-dimensional quantitative
      structure activity relationship (3D-QSAR) model. The obtained 3D-QSAR model has
      an excellent correlation coefficient value (r(2)= 0.96), Fisher ratio (F = 131.9)
      and exhibited good predictive power (q(2) = 0.79). The QSAR model suggests that
      the inclusion of hydrophobic substituents will enhance the Tpl2 kinase
      inhibition. In addition, H-bond donating groups, negative ionic groups and
      electron withdrawing groups positively contribute to the Tpl2 kinase inhibition.
      Further, pharmacophoric model was validated by the receiver operating
      characteristic curve analysis and was employed for virtual screening to identify
      six potential Tpl2 kinase inhibitors. The findings of this study provide a set of
      guidelines for designing compounds with better Tpl2 kinase inhibitory potency.

PMID- 21851208
TI  - Image-guided tumor-selective radioiodine therapy of liver cancer after systemic
      nonviral delivery of the sodium iodide symporter gene.
AB  - We reported the induction of tumor-selective iodide uptake and therapeutic
      efficacy of (131)I in a hepatocellular carcinoma (HCC) xenograft mouse model,
      using novel polyplexes based on linear polyethylenimine (LPEI), shielded by
      polyethylene glycol (PEG), and coupled with the epidermal growth factor receptor
      specific peptide GE11 (LPEI-PEG-GE11). The aim of the current study in the same
      HCC model was to evaluate the potential of biodegradable nanoparticle vectors
      based on pseudodendritic oligoamines (G2-HD-OEI) for systemic sodium iodide
      symporter (NIS) gene delivery and to compare efficiency and tumor specificity
      with LPEI-PEG-GE11. Transfection of HCC cells with NIS cDNA, using G2-HD-OEI,
      resulted in a 44-fold increase in iodide uptake in vitro as compared with a 22
      fold increase using LPEI-PEG-GE11. After intravenous application of G2-HD-OEI/NIS
      HCC tumors accumulated 6-11% ID/g (123)I (percentage of the injected dose per
      gram tumor tissue) with an effective half-life of 10 hr (tumor-absorbed dose, 281
      mGy/MBq) as measured by (123)I scintigraphic gamma camera or single-photon
      emission computed tomography computed tomography (SPECT CT) imaging, as compared
      with 6.5-9% ID/g with an effective half-life of only 6 hr (tumor-absorbed dose,
      47 mGy/MBq) for LPEI-PEG-GE11. After only two cycles of G2-HD-OEI/NIS/(131)I
      application, a significant delay in tumor growth was observed with markedly
      improved survival. A similar degree of therapeutic efficacy had been observed
      after four cycles of LPEI-PEG-GE11/(131)I. These results clearly demonstrate that
      biodegradable nanoparticles based on OEI-grafted oligoamines show increased
      efficiency for systemic NIS gene transfer in an HCC model with similar tumor
      selectivity as compared with LPEI-PEG-GE11, and therefore represent a promising
      strategy for NIS-mediated radioiodine therapy of HCC.

PMID- 21851210
TI  - Ranitidine induces inhibition and structural changes in sucrase.
AB  - Ranitidine is an antagonist of histamine-2 (H(2)) receptor. It is employed to
      treat peptic ulcer and other conditions in which gastric acidity must be reduced.
      Sucrase is a hydrolytic enzyme that catalyzes the breakdown of sucrose to its
      monomer content. A liquid of yeast sucrase was developed for treatment of
      congenital sucrase-isomaltase deficiency (CSID) in human. In this study, the
      effect of ranitidine on yeast sucrase activity was investigated. Our results
      showed that ranitidine binds to sucrase and inhibits the enzyme in a
      noncompetitive manner. The K(i) and IC(50) values were measured to be about 2.3
      and 2.2 mM, respectively. Fluorescence measurement showed conformational changes
      after binding of ranitidine to the enzyme. The fluorescence spectra showed that
      ranitidine could bind to both free enzyme and enzyme-substrate complex, which was
      accompanied with reduction of emission intensity and red shift production.

PMID- 21851211
TI  - Pistagremic acid a new leishmanicidal triterpene isolated from Pistacia
      integerrima Stewart.
AB  - The present study was designed to investigate the whole plant of Pistacia
      integerrima Stewart in order to examine the pharmacological basis of the use of
      the plant in folk medicine for the treatment of infectious diseases and disorder.
      Phytochemical and pharmacological studies led to the isolation of a new
      triterpene pistagremic acid (3-methyl-7-(4,4,10,13,14-pentamethyl-3
      2,3,4,5,6,7,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17
      yl)-oct-3-enoic). Pistagremic acid showed significant leishmanicidal activity
      (IC(50): 6.71 +/- 0.09 uM) against Leishmania major (DESTO) promastigotes in
      comparison to standard compound amphotericin B (IC(50): 0.21 +/- 0.06 uM).

PMID- 21851212
TI  - Effects of some drugs on human cord blood erythrocyte carbonic anhydrases I and
      II: an in vitro study.
AB  - In this [corrected] study, we purified hcbCA I and II from human cord blood
      erythrocytes using [corrected] Sepharose-4B-l [corrected] tyrosine-sulfanilamide
      affinity gel chromatography. [corrected]. The inhibition effects of ampicillin
      sulfate, ceftriaxone, ceftizoxime and ranitidine on hcbCA I and hcbCA II were
      also monitored. [corrected]. IC(50) values for ceftriaxone, ceftizoxime and
      ranitidine were found to be 27.l, 79.4 and 55.5 uM, respectively, [corrected] for
      hcbCA I, and [corrected] 21.0, 79.1 and 66.1 uM, respectively, [corrected] for
      hcbCA II. [corrected]. According to these results, ampicillin [corrected] sulfate
      inhibited only hcbCAII and IC(50) value [corrected] of this antibiotic was found
      to be 56.8 uM. All [corrected] substances were found to be [corrected] non
      competitive inhibitors. It is important to study the inhibition effects of these
      drugs on hcbCA I and II izoenzymes as pregnant women are often prescribed these
      antibiotics. [corrected]. For this reason, the dosage of [corrected] these drugs
      should be carefully evaluated [corrected] to minimize side effects.

PMID- 21851213
TI  - Design, synthesis and biological evaluation of novel quinazoline derivatives as
      potential anti-cancer agents.
AB  - Twenty-two quinazoline derivatives have been synthesised and examined for their
      anti-tumour activity against three tumour cell lines, namely human breast cancer
      cell line (MCF-7), human cervical cancer cell line (HeLa) and human hepatoma cell
      line (HepG2). Twelve of the tested compounds have shown promising anti-tumour
      activity with an IC(50) range of 5.0-9.7 ug/mL. Regarding the spectrum of
      activity, five compounds exhibited interesting anti-proliferative properties
      against the three tested cell lines comparable to the reference drug (dasatinib).

PMID- 21851214
TI  - Protective effects of diosmetin extracted from Galium verum L. on the thymus of
      U14-bearing mice.
AB  - Diosmetin (DGVL) extracted from the traditional Chinese herb Galium verum L. has
      been found to have anticancer activity. In this study, the effects of DGVL on the
      thymus of U14-bearing mice were investigated. Using flow cytometry, peripheral
      blood lymphocytes were characterized based on the expression of surface markers
      for T helper cells (CD4(+)) and T suppressor cells (CD8(+)). Serum levels of
      tumor necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2), IL-10, and
      transforming growth factor beta1 (TGF-beta1) and a cell proliferation assay were
      determined with an enzyme-linked immunosorbent assay. The expression of Fas and
      Fas ligand (FasL) on the thymus was determined by Western blotting. Our results
      showed that DGVL inhibited tumor growth and significantly increased the thymus
      weight compared with the control. Also, DGVL elevated serum levels of IL-2 and
      significantly reduced levels of TNF-alpha, TGF-beta1, and IL-10 in a dose
      dependent manner. Histological study and terminal dUTP nick end labeling staining
      results showed that DGVL protected thymus tissue against the onslaught of tumor
      growth by inhibiting thymus lymphocyte apoptosis. The cell proliferation assay
      revealed that DGVL might promote more thymus lymphocytes towards proliferation.
      Furthermore, the ratio of CD4(+)/CD8(+) T lymphocytes was significantly increased
      from 0.69 to 2.29 by treatment with DGVL. Immunoblotting analyses revealed that
      the expression of Fas and FasL on the thymus was lower in mice in the DGVL
      treatment group than in the control mice. In conclusion, DGVL can inhibit tumor
      growth and protect tumor-induced apoptosis of the thymus, and the mechanism is
      closely associated with reduced cell death in the thymus and a Fas-FasL-dependent
      pathway.

PMID- 21851215
TI  - A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed
      or relapsed and refractory multiple myeloma.
AB  - Abstract   A phase 1 study of IPI-504 (retaspimycin hydrochloride) administered
      intravenously twice weekly for 2 weeks at 22.5, 45, 90, 150, 225, 300 or 400
      mg/m(2) followed by 10 days off-treatment was conducted to determine the safety
      and maximum tolerated dose (MTD) of IPI-504 in patients with relapsed or
      relapsed/refractory multiple myeloma (MM). Anti-tumor activity and
      pharmacokinetics were also evaluated. Eighteen patients (mean age 60.5 years;
      median 9 prior therapies) were enrolled. No dose-limiting toxicities (DLTs) were
      reported for IPI-504 doses up to 400 mg/m(2). The most common treatment-related
      adverse event was grade 1 infusion site pain (four patients). All other treatment
      related events were assessed as grade 1 or 2 in severity. The area under the
      curve (AUC) increased with increasing dose, and the mean half-life was
      approximately 2-4 h for IPI-504 and its metabolites. Four patients had stable
      disease, demonstrating modest single-agent activity in relapsed or
      relapsed/refractory MM.

PMID- 21851216
TI  - Importance of immunoglobulin heavy chain variable region mutational status in
      del(13q) chronic lymphocytic leukemia.
AB  - Among prognostic factors for chronic lymphocytic leukemia (CLL), immunoglobulin
      heavy chain variable region (IGHV) mutation status and DNA analysis appear to be
      the most important. However, there is limited clinical outcome information for
      patients with the favorable-risk del(13q) and poor-risk unmutated IGHV. We
      retrospectively screened all patients with CLL at our institution between 2004
      and June 2010 for del(13q) who also had an IGHV analysis. Unmutated IGHV was
      found in 38/79 patients; age, Rai stage, prior therapy, and time to evaluation
      were similar to those for patients with mutated IGHV. Unmutated patients were
      nearly four times more likely to harbor additional chromosomal aberrations
      compared to mutated patients (p < 0.001). During a median follow-up of 4.5 years,
      unmutated patients were more likely to demonstrate Rai stage progression (69% vs.
      31%, log-rank p < 0.001) and to receive treatment (5-year cumulative probability
      of treatment: 65% vs. 32%, p < 0.001). Patients with unmutated CLL also had a
      shorter overall survival (5-year survival probability: 72% vs. 100%, p < 0.001).
      When limiting analysis to the 47 patients with del(13q) as a sole chromosomal
      abnormality, the 13 (28%) unmutated patients were more likely to demonstrate Rai
      progression (p < 0.001), to receive treatment (p = 0.02), and to have a shorter
      overall survival (p = 0.13) than the 34 mutated patients. These data suggest that
      del(13q) conveys an indolent course only in patients with IGHV-mutated CLL.

PMID- 21851217
TI  - Chronic myelogenous leukemia diagnosed in two patients with breast cancer.

PMID- 21851218
TI  - Update on the molecular pathogenesis and clinical treatment of mantle cell
      lymphoma: report of the 10th annual conference of the European Mantle Cell
      Lymphoma Network.
AB  - Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma
      characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in
      constitutional overexpression of cyclin D1 and cell cycle dysregulation in
      virtually all cases. Clinically, MCL shows an aggressive clinical course with a
      continuous relapse pattern and a median survival of only 3-5 years. However,
      recently a subset of up to 15% long-term survivors has been identified with a
      rather indolent clinical course. Advanced stage disease is usually apparent
      already at first clinical manifestation; in general, conventional chemotherapy is
      only palliative and median duration of remissions is only 1-2 years. In 2000, the
      European MCL Network ( http://www.european-mcl.net ) was founded, which consists
      of 15 national lymphoma study groups supplemented by experts in hematopathology,
      cytogenetics and molecular genetics. During the last decade, the European
      consortium has successfully initiated the largest phase III trials in MCL
      worldwide. In the current study generation, the addition of high-dose Ara-C to a
      rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)
      like regimen followed by myeloablative consolidation achieved a significant
      improvement of progression-free survival. Similarly, in elderly patients,
      rituximab maintenance until progression led to a marked prolongation of remission
      duration. Emerging strategies include proteasome inhibitors, immune modulatory
      drugs (IMiDs), mammalian target of rapamycin (mTOR) inhibitors and others, all
      based on the dysregulated control of cell cycle machinery and impairment of
      several apoptotic pathways. Combination strategies are currently being
      investigated in numerous trials, but their introduction into clinical practice
      and current treatment algorithms remains a challenge. Future strategies will
      apply individualized approaches according to the molecular risk profile of the
      patient. At the annual conference in Warsaw, recent results of molecular
      pathogenesis, analyses of current clinical trials and new study concepts were
      discussed.

PMID- 21851219
TI  - Lower incidence of plasma cell neoplasm is maintained in migrant Chinese to
      British Columbia: findings from a 30-year survey.
AB  - The etiology of plasma cell myeloma (PCM) is largely unknown. Its incidence
      varies widely in different ethnic groups. Migrant study may help determine the
      relative contributions of genetic versus environmental factors to PCM
      pathogenesis. We performed a retrospective review of the computerized records of
      all patients diagnosed with PCM between 1975 and 2004 in British Columbia (BC),
      and identified patients of Chinese ethnicity. This was compared with PCM
      incidence in Hong Kong (HK) Chinese. Age distributions of HK, BC and BC Chinese
      populations were obtained from the census departments to calculate world age
      standardized rates (WASRs). The WASR of PCM over the 30-year period in BC Chinese
      was 1.64/100 000 person-years (95% confidence interval [CI] 1.37-1.93). This was
      similar to the WASR observed in HK (1.78, 95% CI 1.73-1.83), with a standardized
      incidence ratio (SIR) of 0.91 (95% CI 0.74-1.10). The rate was much lower than
      that in the BC non-Chinese background population (WASR 3.59, 95% CI 3.50-3.68;
      SIR 0.46, 95% CI 0.38-0.56). The lower rates in BC Chinese were maintained across
      all years, both genders and in all age groups above 45 years. Our observations
      suggest a strong genetic component as the cause of differences in the ethnic
      predisposition to PCM.

PMID- 21851220
TI  - Coping styles, health status and advance care planning in patients with
      hematologic malignancies.
AB  - This study evaluated whether measures of psychological well-being, including
      coping style, are associated with advance care planning (ACP). Data were from the
      Hematology Communications Study (HEMA-COMM), a prospective observational study of
      physician-patient communication in patients with hematologic malignancies. ACP
      was defined as having a living will, having a health care proxy, discussing life
      support with family or friends and discussing life support with a doctor or
      nurse. A total of 293 patients participated: only 45 (15%) had all the elements
      of ACP; 215 (73%) had at least one element of ACP, while 33 (11%) did not engage
      in ACP. In multivariate analysis, specific coping styles but not other measures
      of psychosocial well-being were associated with having written ACP. Verbal ACP
      was associated with patient-reported health and physician estimate of life
      expectancy. Our study suggests that tailoring ACP discussions to a patient's
      coping style may increase engagement in ACP.

PMID- 21851221
TI  - Expression of cyclin A and bone morphogenetic protein receptors and response to
      induction therapy in patients with acute leukemias.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional cytokines that belong to
      the transforming growth factor beta (TGFbeta) family. They participate in the
      regulation of growth, differentiation and apoptosis in a variety of cell types
      including hematopoietic lineages. To date, the role of BMPs in carcinogenesis has
      not been well known. Cyclin A is a cell cycle regulatory protein which plays the
      role of a parameter of cell proliferation in various types of carcinomas
      including hematological malignancies. The role of BMPRIA, BMPRIB, BMPRI and
      cyclin A in the pathogenesis of acute leukemias remains unclear. The aim of this
      study was to evaluate the expression of BMP receptors and cyclin A on blast cells
      and their possible relationship with clinical outcome. Seventy patients with
      acute leukemias (28 female and 42 male) and 10 aged-matched healthy controls were
      studied. All patients were examined before cytostatic treatment. The expression
      of BMP receptors and cyclin A was detected by flow cytometry. The results show
      that higher expression of BMPRIA, BMPRIB, BMPRII and cyclin A is related with a
      higher complete response (CR) rate, higher overall survival (OS) and lower
      relapse risk. The expressions of BMPRIA, BMPRIB, BMPRII and cyclin A could be
      useful as prognostic parameters of the proliferation status of acute leukemia
      cells, but further studies are needed to assess this phenomenon.

PMID- 21851222
TI  - Growth factor- and adhesion protein-like components of fetal calf serum can
      significantly enhance the intracellular delivery of Peptide nucleic acids.
AB  - Evidence is presented that components of fetal calf serum (FCS) can significantly
      enhance the splicing correction activity of peptide nucleic acids (PNA) in HeLa
      pLuc 705 cells. The effect proved more pronounced for PNAs bearing fluorescence
      tags and relies on the ability of specific components of FCS to mediate a mainly
      nonendocytotic intracellular delivery of PNA. Attempts to isolate and
      characterize the active serum components using PNA-loaded beads and nano-LC-ESI
      mass spectrometry revealed the growth-factor related inter-alpha-trypsin
      inhibitor and the adhesion protein fibronectin to be substantially responsible
      for the delivery activity of FCS.

PMID- 21851223
TI  - Long-term systemic administration of unconjugated morpholino oligomers for
      therapeutic expression of dystrophin by exon skipping in skeletal muscle:
      implications for cardiac muscle integrity.
AB  - Duchenne muscular dystrophy (DMD) is a lethal X-linked inherited disease caused
      by mutations in the dystrophin gene and consequent lack of dystrophin in the
      skeletal, cardiac, and smooth musculature and in the nervous system. Patients die
      during their mid-twenties because of severe muscle loss and life-threatening
      respiratory and cardiac complications. The splicing modulation approach mediated
      by antisense oligonucleotides can restore the production of a partially
      functional quasi-dystrophin in skeletal muscles. We recently showed that a
      chronic, 12-month treatment with phosphorodiamidate morpholino oligomers
      efficiently restored dystrophin in widespread skeletal muscles and led to normal
      locomotor activity indistinguishable from that of dystrophin-expressing C57 mice.
      However, no detectable dystrophin expression was observed in the hearts of
      treated mice. In the present study, histological analyses show a more severe
      cardiac pathology compared with untreated animals in the face of enhanced
      locomotor behavior. This observation implies that the increase in locomotor
      activity of treated mdx mice may have a paradoxical detrimental effect on the
      dystrophic heart. In the context of skeletal muscle-centric therapies for DMD,
      our data suggest that particular vigilance should be instigated to monitor
      emergence of accelerated cardiac dysfunction.

PMID- 21851224
TI  - Beyond diagnosis- and therapy-centred therapy: the case for incorporating
      contextual factors in psychotherapy treatment planning.
AB  - OBJECTIVE: The purpose of this paper is to outline a basic approach to
      psychotherapy treatment selection, with an emphasis on the role of contextual
      factors. METHOD: Observations and suggestions are based on clinical work and
      reading of the psychiatric literature. CONCLUSION: It is preferable to organize
      psychotherapy treatment selection around a consideration of case formulation and
      contextual factors rather than just diagnosis or a general preference for a
      purportedly superior type of therapy.

PMID- 21851225
TI  - Mental health, criminal justice and culture: some ways forward?
AB  - OBJECTIVE: This paper aims to offer an overview of the mental health needs of
      Indigenous men and women in the criminal justice system and how Indigenous
      cultural perspectives on mental health might influence forensic mental health
      service provision. CONCLUSION: There is a need for both mental health and
      criminal justice agencies to collaborate more closely in developing new models of
      service provision that incorporate Indigenous perspectives on social and
      emotional wellbeing, recognize culturally specific mental health risk and
      protective factors in relation to prevention, early intervention and treatment,
      and take advantage of the opportunities for treatment that arise in the context
      of criminal justice system intervention.

PMID- 21851226
TI  - Repatriation of a patient under a forensic order from Australia to Thailand.
AB  - OBJECTIVE: A person who develops a serious mental illness whilst visiting
      Australia may encounter substantial barriers to treatment, rehabilitation and
      eventual repatriation to his home country. Particularly when English is not the
      person's first language and there are no supports in Australia, the person will
      have special needs whilst recovering from his or her illness. Further
      difficulties arise if the person has been charged with a serious offence. METHOD:
      We present the case of a 23 year old single Thai citizen who had been living in
      Australia on an overseas student visa before he was charged with a serious
      violent offence in the context of a mental illness. RESULTS: Following an
      assessment at the watch-house, the patient was diagnosed with an untreated
      psychotic illness. The patient was subsequently admitted from a remand prison to
      a secure mental hospital and became subject to the involuntary treatment
      provisions of the Queensland Mental Health Act. CONCLUSIONS: With a detailed
      multi-disciplinary rehabilitation plan and the assistance of a transcultural
      mental health service, a patient with a serious mental illness may be
      rehabilitated to enable negotiations with multiple government and non-government
      agencies to facilitate the patient's return to his country of origin.

PMID- 21851227
TI  - On the language surrounding the psychiatrist-as-expert.
AB  - OBJECTIVE: This paper responds to two articles in a recent issue of Australasian
      Psychiatry examining the names given to clinicians and forensic experts, and to
      the people to whom we give service. CONCLUSIONS: The contextual issues that
      confront the psychiatrist-as-expert differ from those as the psychiatrist-as
      therapist in certain important ways. The alteration of the name from patient into
      one more descriptive of their position, such as defendant or claimant, is
      protective for both the assessor and the assessed. It reminds all that the nature
      of the relationship is not primarily therapeutic.

PMID- 21851228
TI  - Alcohol and substance use by patients with psychosis presenting to an emergency
      department: changing patterns.
AB  - OBJECTIVES: The aim of this study was to determine the incidence of alcohol and
      other substance use in patients presenting to an emergency department with acute
      psychiatric illnesses and to clarify the role of urine drug screens. METHOD: This
      was an unblinded prospective (observational) cohort study incorporating
      retrospective review of patient medical records, history of alcohol and substance
      use, results of urine drug screens and blood alcohol concentrations. RESULTS: Of
      196 acute psychotic patients, 104 were diagnosed with schizophrenia and 92 with
      "other psychosis". Results of urine drug screens were consistent with self
      reported use of substances and only identified an additional 5% of substance
      users. Cannabis was the commonest illicit substance used by both groups of
      patients, followed by psychostimulants, mainly amphetamines. Younger males were
      more likely to use psychostimulants and to present with violence. CONCLUSIONS:
      Patients with co-existing mental health problems and substance use present a
      major problem for our emergency departments. Cannabis was the most common
      substance used. Youth, male gender and psychostimulant use are associated with
      violent presentations. A comprehensive history of alcohol and substance use is
      important to implement appropriate dual diagnosis treatment. Urine drug screening
      is recommended for patients who do not admit to substance use.

PMID- 21851229
TI  - The salutary effects of DHA dietary supplementation on cognition,
      neuroplasticity, and membrane homeostasis after brain trauma.
AB  - The pathology of traumatic brain injury (TBI) is characterized by the decreased
      capacity of neurons to metabolize energy and sustain synaptic function, likely
      resulting in cognitive and emotional disorders. Based on the broad nature of the
      pathology, we have assessed the potential of the omega-3 fatty acid
      docosahexaenoic acid (DHA) to counteract the effects of concussive injury on
      important aspects of neuronal function and cognition. Fluid percussion injury
      (FPI) or sham injury was performed, and rats were then maintained on a diet high
      in DHA (1.2% DHA) for 12 days. We found that DHA supplementation, which elevates
      brain DHA content, normalized levels of brain-derived neurotrophic factor (BDNF),
      synapsin I (Syn-1), cAMP-responsive element-binding protein (CREB), and
      calcium/calmodulin-dependent kinase II (CaMKII), and improved learning ability in
      FPI rats. It is known that BDNF facilitates synaptic transmission and learning
      ability by modulating Syn-I, CREB, and CaMKII signaling. The DHA diet also
      counteracted the FPI-reduced manganese superoxide dismutase (SOD) and Sir2 (a
      NAD+-dependent deacetylase). Given the involvement of SOD and Sir2 in promoting
      metabolic homeostasis, DHA may help the injured brain by providing resistance to
      oxidative stress. Furthermore, DHA normalized levels of calcium-independent
      phospholipase A2 (iPLA2) and syntaxin-3, which may help preserve membrane
      homeostasis and function after FPI. The overall results emphasize the potential
      of dietary DHA to counteract broad and fundamental aspects of TBI pathology that
      may translate into preserved cognitive capacity.

PMID- 21851230
TI  - Time- and dose-dependent neuroprotective effects of sex steroid hormones on
      inflammatory cytokines after a traumatic brain injury.
AB  - Following a traumatic brain injury (TBI), excessive release of proinflammatory
      cytokines is the major cause of cerebral edema and neuronal loss. This study was
      designed to examine changes in concentrations of some proinflammatory cytokines
      including interleukin-1 beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta)-in a rat
      model of TBI in which the animals were treated with different doses of estrogen
      or progesterone 6 and 24 h after the TBI. Adult female rats were divided into 14
      groups. Hormones or vehicle were given intraperitoneally 30 min after a moderate
      TBI was induced by the Marmarou method. The levels of proinflammatory cytokines
      in brain were measured at 6 and 24 h after the TBI. A high dose of estrogen (E2)
      or a low dose of progesterone (P1) increased brain levels of IL-1beta 52.7% and
      79.2% respectively at 6 h after the TBI. By 24h, IL-1beta levels in the brain
      were 27.5% and 27% lower following administration of estrogen low dose (E1) or
      E2, respectively. High-dose administration of progesterone reduced brain levels
      of IL-6 to 45.9% at 6 h after the TBI, and P1 and E1 treatment significantly
      decreased IL-6 levels at 24 h. Brain levels of TNF-alpha were 72.5% lower at 6 h
      after the TBI following P2 treatment and 48.5% higher at 24 hrs following
      treatment with E2. The levels of TGF-beta were also 3.37 times higher 24 h after
      the TBI following treatment with E1. Both doses of the hormones tested increases
      TGF-beta levels 6 h after the TBI. Based on our findings, we conclude that
      progesterone and estrogen influence the levels of proinflammatory cytokines
      either at the primary or secondary stages after a TBI. Accordingly, this study
      suggests a mechanism by which hormones reduce cerebral edema.

PMID- 21851231
TI  - Monoclonal antibodies for the identification and purification of vNAR domains and
      IgNAR immunoglobulins from the horn shark Heterodontus francisci.
AB  - In addition to conventional antibodies, cartilaginous fish have evolved a
      distinctive type of immunoglobulin, designated as IgNAR, which lacks the light
      polypeptide chains and is composed entirely by heavy chains. IgNAR molecules can
      be manipulated by molecular engineering to produce the variable domain of a
      single heavy chain polypeptide (vNARs). These, together with the VHH camel
      domains, constitute the smallest naturally occurring domains able to recognize an
      antigen. Their special features, such as small size, long extended finger-like
      CDR3, and thermal and chemical stability, make them suitable candidates for
      biotechnological purposes. Here we describe the generation of two mouse
      monoclonal antibodies (MAbs), MAb 370-12 and MAb 533-10, that both specifically
      react with vNAR domains of the horn shark Heterodontus francisci. While the
      former recognizes a broad spectrum of recombinant vNAR proteins, the latter is
      more restricted. MAb 370-12 precipitated a single band from whole shark serum,
      which was identified as IgNAR by mass spectrometry. Additionally, we used MAb 370
      12 to follow the IgNAR-mediated immune response of sharks during immunization
      protocols with two different antigens (complete cells and a synthethic peptide),
      thus corroborating that MAb 370-12 recognizes both isolated vNAR domains and
      whole IgNAR molecules. Both MAbs represent an affordable molecular, biochemical,
      and biotechnological tool in the field of shark single-domain antibodies.

PMID- 21851232
TI  - Expression of Mycobacterium tuberculosis ferric uptake regulator A gene in
      Escherichia coli and generation of monoclonal antibodies to FurA.
AB  - Ferric uptake regulator A of Mycobacterium tuberculosis (MTB), which belongs to
      the Fur superfamily, is situated immediately upstream of katG encoding catalase
      peroxidase, a major virulence factor that also activates the pro-drug isoniazid.
      The feature and role of FurA in oxidative stress contribute to research on the
      pathogenesis of mycobacteria. In this study, four novel mouse monoclonal
      antibodies were generated using the prokaryotically expressed FurA protein as
      immunogen. The furA gene of M. tuberculosis H37Rv was inserted into a bacterial
      expression vector of pRSET-A and effectively expressed in Escherichia coli
      BL21(DE3). The expressed fusion protein existed as soluble form in cell lysates
      and was purified via Ni-NTA purification system. Using the fusion protein to
      immunize BALB/c mice, four monoclonal antibodies (H9H6, H9E12, H10H6, and H10H8)
      were produced. As shown by Western blot analysis and cell fluorescence microscopy
      assay, the four antibodies could recognize the FurA protein, respectively. Then
      we assessed the effect of iron on the expression of FurA in MTB H37Rv and we
      concluded that iron does not affect FurA expression. These results suggest that
      the antibodies against FurA may provide a powerful tool for elucidating FurA
      biofunctions and regulation mechanism in the pathogenesis of tuberculosis.

PMID- 21851233
TI  - High-level expression of Mycobacterium tuberculosis protein EspB in E. coli and
      preparation of novel anti-EspB monoclonal antibodies.
AB  - The ESX-1 secretion system plays a critical role in the virulence of
      Mycobacterium tuberculosis. The ESX-1 secreted protein EspB is cleaved close to
      its C-terminus during secretion and is necessary for inhibiting phagosome
      maturation. In this study, the EspB gene of M. tuberculosis H37Rv was cloned into
      the expression vector of pET21a(+) and was effectively expressed in Escherichia
      coli BL21(DE3). The expressed fusion protein existed as a soluble form in cell
      lysate and was first purified by a column packed with Ni-NTA resin and then a
      column packed with DEAE-Sepharose Fast Flow matrix. Using the purified protein to
      immunize BALB/c mice, five monoclonal antibodies were produced. As shown by ELISA
      and immunoblotting, the five respective antibodies could recognize the EspB
      protein. These monoclonal antibodies will provide powerful reagents for further
      investigation of EspB protein functions.

PMID- 21851234
TI  - Characterization of novel murine monoclonal antibodies directed against the
      extracellular domain of human HER2 tyrosine kinase receptor.
AB  - HER2 proto-oncogene encodes a transmembrane receptor tyrosine kinase
      overexpressed in a variety of solid tumors. Several mouse monoclonal antibodies
      (MAbs) have been developed that recognize the extracellular part of HER2; of them
      two MAbs were humanized and employed for targeted immunotherapy. In this study we
      aimed to produce murine MAbs that specifically recognize the extracellular domain
      of human HER2. BALB/c mice were first primed with HER2-transfected NIH-3T3 cells
      and then boosted with recombinant extracellular part of HER2. Splenocytes from
      hyperimmunized mice were fused with myeloma cells and growing hybridomas were
      selected and screened for HER2 reactivity by an indirect ELISA. HER2-specific
      hybridomas were selected, cloned by limiting dilution assay, and further
      characterized by Western blotting and flow cytometry techniques. All clones
      showed positive reactivity to HER2 with binding affinity, ranging from 1.9*10(8)
      to 5*10(9), and stained HER2-transfected cells and malignant cells overexpressing
      HER2. None of the MAbs inhibited the binding of trastuzumab (Herceptin((r))) to
      HER2, indicating recognition of distinct epitopes by these MAbs. Based on these
      findings, our MAbs could be potentially used for selective targeting of HER2
      expressing malignancies.

PMID- 21851235
TI  - Development and characterization of a mouse monoclonal antibody against
      antimicrobial peptide tachyplesin I.
AB  - Monoclonal antibodies against tachyplesin I (TP I) were developed to study its
      mechanisms of activity, a kind of cationic antimicrobial peptides (AMPs), in vivo
      or in vitro, and to purify TP I from expression products. The synthesized TP I
      was chemically conjugated with the carrier protein BSA and then injected into
      BALB/c mice. Positive hybridomas were screened by indirect enzyme-linked
      immunosorbent assay (ELISA) using TP I and subcloned three times with limiting
      dilution. Five MAbs effective in detecting the native TP I (named 2D8, 3B8, 5H2,
      6B12, and 8F5) were obtained. Isotyping of all obtained MAbs indicated that MAbs
      2D8, 3B8, 5H2, and 8F5 belong to IgG1, and MAb 6B12 belongs to IgG2a. Specificity
      assay showed that MAb 8F5 had almost the same level of specificity to natural TP
      I, recombinant TP I, and synthesized TP I and TP II, but did not cross-react with
      control peptides. These results suggest that the synthetic AMP conjugates can
      elicit antibodies against native AMPs and can be used to detect antimicrobial
      peptides.

PMID- 21851236
TI  - Immunoreactivity of two novel monoclonal antibodies against human inducible co
      stimulator ligand.
AB  - Human inducible co-stimulator ligand (GL50, CD275), also known as B7-H2 or ICOSL,
      is a positive co-stimulatory molecule of B7/CD28 superfamily, which plays a
      critical role in immune response. Here we generated two novel mouse anti-human
      GL50 monoclonal antibodies (MAbs) using classical hybridoma technology. The two
      MAbs (clones 2B4 and 4D11) were IgG1 (kappa) and IgG2a (kappa), respectively, and
      bound specifically to human GL50. Epitope competition assay showed that 2B4 and
      4D11 bind to the same epitope of GL50, which is not recognized by the
      commercially available GL50 MAb (9F-8A4). Functionally, the two MAbs act as a
      blocker of T cell proliferation. Taken together, as useful tools, these two
      antibodies might be of great value for further exploration of the immune
      identification and function of GL50.

PMID- 21851237
TI  - Monoclonal antibody against NRP-1 b1b2.
AB  - Neuropilin-1 is a member of the neuropilins family protein, which contains a
      large extracellular domain (a1a2, b1b2 and c), a single transmembrane domain, and
      a short cytoplasmic tail. NRP-1 plays a critical role in angiogenesis and
      stimulates endothelial cell division and migration by binding VEGF(165) with b1b2
      domain. In the present study, we report the establishment of a monoclonal
      antibody (A6-26-11-26 clone) specific for NRP-1 b1b2 through hybridoma method.
      Western blot analysis indicates that our NRP-1 b1b2 MAb can combine both NRP-1
      b1b2 and NRP-1 originated from tumor cells. This monoclonal antibody against NRP
      1 b1b2 will be useful in the further development of cancer target strategy.

PMID- 21851238
TI  - Development of a monoclonal antibody against glucosyltransferase D of
      Streptococcus mutans GS 5.
AB  - Glucosyltransferases GtfB, GtfC, and GtfD of Streptococcus mutans are virulent
      factors involved in dental caries. Consequently, they are considered to be target
      molecules in the development of vaccines against dental caries. Among them, GtfD
      plays a significant role in the sucrose-dependent cellular adhesion of S. mutans,
      and a number of studies have suggested that the N-terminus of GtfD is an
      important part of its role in enzymatic activity. In this study, we generated
      monoclonal antibodies against the N-terminus of GtfD (anti-GtfDN antibody) in an
      initial attempt to investigate its preventive efficacy against dental caries. To
      obtain anti-GtfDN monoclonal antibodies, the gene for the N-terminus of gtfD (2
      kb) was cloned into an Escherichia coli expression vector, pQE30; then the
      expressed protein (about 75 kDa) was purified. The purified GtfDN protein was
      injected into BALB/c mice, and hybridoma clones were established. We obtained
      three hybridoma clones (HDN9, HDN11, and HDN28) capable of producing anti-GtfDN
      antibodies. Their binding specificity was characterized by ELISA, dot blot, and
      Western blot analysis after purification using affinity column chromatography.
      The isotype of the monoclonal antibodies was confirmed to be IgG2a.

PMID- 21851239
TI  - Monoclonal antibodies to sea cucumber polysaccharide and their use in a sandwich
      ELISA assay.
AB  - Antigen was synthesized with L-SCP, a sea cucumber polysaccharide isolated from
      Pearsonothuria graeffei (Semper) and bovine serum albumin (BSA) as a carrier
      protein. Spleen cells with high titer antibody producing ability were removed and
      fused with myeloma cells of SP2/0-Ag14 origin. Three stable murine monoclonal
      antibodies (MAb ascites) producing cell lines to L-SCP were generated according
      to a conventional immunization protocol. Their epitope mapping and binding
      specificity, which was characterized by blocking and inhibition enzyme-linked
      immunosorbent assay (ELISA) indicated that these specific MAb ascites have
      similar binding patterns. A sandwich ELISA was developed on the basis of
      employing L-SCP specific antibodies including MAb 3G6 as capture antibody and HRP
      3G6 as detection antibody. The working range for L-SCP in aqueous solution from
      this method was 100-10,000 ng/mL with good sensitivity, specificity, and
      precision (relative standard deviation <=7.9%). Thus the developed ELISA can be
      used as a convenient tool for the rapid detection of L-SCP in biological examples
      in the future.

PMID- 21851240
TI  - A monoclonal antibody for in vivo detection of peroxisome-associated PTS1
      receptor.
AB  - PEX5 is a key protein of the peroxisomal protein import machinery. This cycling
      receptor binds newly synthesized proteins with a peroxisomal targeting signal
      type 1 in the cytosol and directs them to the peroxisomal membrane. There, PEX5,
      together with its docking protein, forms a transient membrane-spanning channel
      that enables cargo-transport across the membrane. Through interaction with other
      multimeric membrane complexes, the receptor is released from the membrane back to
      the cytosol. Very little is known about the various conformational states of the
      receptor during its cycling. Here we report the generation and characterization
      of a mouse monoclonal antibody that recognizes in vivo primarily the membrane
      associated form of the human PTS1 receptor.

PMID- 21851241
TI  - Preparation of novel anti-ski monoclonal antibodies.
AB  - Ski is an avian sarcoma virus oncogene homolog best known for inhibiting TGF beta
      signaling through its association with the SMAD proteins. Anti-Ski antibodies
      (MAbs) of high titer were prepared by immunizing BALB/c mice with multifocal
      intradermal injections and fusing high titer antibody producing spleen cells with
      myeloma cells of SP2/0 origin. Three MAbs were selected for further
      characterization as classes and subclasses. Antibodies were produced by these
      three clones with high affinities ranging from 10(9) to 10(11)/m. These clones
      were found to be of the immunoglobulin IgG1 and IgG2b subclass with kappa light
      chain. They could recognize Ski as determined by Western blot analysis. The
      produced MAbs will be a useful tool for further investigation of Ski functions in
      organisms.

PMID- 21851242
TI  - Generation of a rat monoclonal antibody specific for hsp72.
AB  - The heat shock protein 70 (Hsp70) family members function as ATP-dependent
      molecular chaperones that assist in the folding of newly synthesized polypeptides
      and in the refolding of misfolded/aggregated proteins. These heat shock proteins
      comprise at least eight sets of molecular groups that share high homology, but
      differ from each other in their expression level and subcellular localization.
      Hsp72, which is also known as Hsp70 and Hsp70-1, is localized mainly in the
      cytoplasm but is also found in the nucleus. Stress-induced Hsp72 functions as a
      chaperone enabling the cells to cope with harmful aggregations of denatured
      proteins during and following stress. The difference in the function of Hsp72
      from that of other Hsp70 members, however, remains unclear. We report the
      establishment of a monoclonal antibody specific for Hsp72 using the rat medial
      iliac lymph node method. Immunoblot analysis revealed that our monoclonal
      antibody against Hsp72 specifically identified the 65 kDa protein.
      Immunocytochemical staining also revealed that Hsp72 localized in the cytoplasm
      and nucleus, and aggregated in the nucleus in response to heat stress. This MAb
      against Hsp72 will allow for further studies to elucidate the mechanism by which
      Hsp72 is localized in the cell in response to stress stimuli, and aid in the
      identification of specific interacting molecules.

PMID- 21851243
TI  - Detection and characterization of 2-E2-specific surface protein in human
      pluripotent stem cells.
AB  - To investigate cell surface antigens on human embryonic stem cells (hESCs), we
      generated a panel of monoclonal antibodies (MAbs) against undifferentiated hESCs
      by a decoy immunization strategy. One of the MAbs, MAb 2-E2, specifically bound
      to human pluripotent stem cells but not to mouse pluripotent stem cells and mouse
      embryonic fibroblasts. 2-E2 also bound to human differentiated cells, peripheral
      blood monocytes, and dermal fibroblasts. 2-E2 antigen expression drastically
      decreased in retinoic acid-induced differentiated hESCs. However, it gradually
      increased after initial decrease during embryoid body formation of hESCs. 2-E2
      recognized approximately 68 and 27 kDa proteins present on the surface of human
      pluripotent stem cells. The results suggest that 2-E2-specific surface protein is
      a novel cell surface protein that plays a role in the early differentiation of
      human pluripotent stem cells.

PMID- 21851248
TI  - Linguistic correlates of social anxiety disorder.
AB  - The goal of this study was to examine the linguistic correlates of social anxiety
      disorder (SAD). Twenty-four individuals with SAD (8 of them with a generalised
      subtype) and 21 non-anxious controls were asked to give speeches in front of an
      audience. The transcribed speeches were examined for the frequency of negations,
      I-statements, we-statements, negative emotion words, and positive emotion words.
      During their speech, individuals with either SAD subtype used positive emotion
      words more often than controls. No significant differences were observed in the
      other linguistic categories. These results are discussed in the context of
      evolutionary and cognitive perspectives of SAD.

PMID- 21851249
TI  - Frames of reference in spatial span.
AB  - In four experiments, a computerized Corsi-like paradigm was used to assess which
      of the many reference frames are used in visuospatial short-term memory. By
      varying the relative orientation (slanted +/-45 degrees  or in an upright
      position) of the head and the displays, we modulate the utility of the
      allocentric, egocentric (eye- and head-centred), and template-centred reference
      frames. The results of all experiments showed the crucial importance of the
      gravitational allocentric reference frames while using visuospatial short-term
      memory to retain a spatial sequence of elements. The results also provide some
      support for a mental rotation process involved in recognition following angular
      displacement of a multi-item display.

PMID- 21851250
TI  - Time-dependent properties of human umbilical fascia.
AB  - This investigation is devoted to the study of the viscoelastic behavior of human
      abdominal fascia from the umbilical region. Seventeen samples 10 mm wide and up
      to 70 mm long were cut along the primary fiber direction (group FL) or
      perpendicular to it (group FT) and subjected to relaxation tests. The
      viscoelastic response of the tissue at three different strain levels (4%, 5%, and
      6%) was investigated. The relaxation curves were fitted using a two-stage
      decaying exponential form. The following parameters were determined: initial
      stress sigma(0), relaxation times tau(1) and tau(2), stress reduction Deltasigma,
      initial relaxation modulus E and equilibrium relaxation modulus E(eq), as well as
      the ratio E/E(eq). Fiber orientation and strain levels were varied to determine
      their influence on the viscoelastic properties of fascia. The results highlight
      the inherent viscoelastic mechanical properties of umbilical fascia. The values
      of the viscoelastic parameters determined for the longitudinal and transverse
      directions varied markedly. Significant differences were found between the two
      groups FL and FT for the initial stress at 5% and 6% strain (p < 0.038) and for
      the initial and equilibrium moduli at the 6% strain level (p < 0.046). The stress
      reduction in samples from the FL group (45-55%) was less than that in samples
      from the FT group (37-54%), but this difference was not significant (p > 0.388).
      The influence of strain level on the parameter values was not statistically
      significant (p > 0.121). The nonlinear response of the tissue was demonstrated
      over the chosen strain range.

PMID- 21851251
TI  - Cognitive vulnerability to depression: a comparison of the weakest link, keystone
      and additive models.
AB  - Multiple theories of cognitive vulnerability to depression have been proposed,
      each focusing on different aspects of negative cognition and utilising different
      measures of risk. Various methods of integrating such multiple indices of risk
      have been examined in the literature, and each demonstrates some promise. Yet
      little is known about the interrelations among these methods, or their
      incremental validity in predicting changes in depression. The present study
      compared three integrative models of cognitive vulnerability: the additive,
      weakest link, and keystone models. Support was found for each model as predictive
      of depression over time, but only the weakest link model demonstrated incremental
      utility in predicting changes in depression over the other models. We also
      explore the correlation between these models and each model's unique contribution
      to predicting onset of depressive symptoms.

PMID- 21851253
TI  - Fibrillin-1 and fibrillin-2 are essential for formation of thick oxytalan fibers
      in human nonpigmented ciliary epithelial cells in vitro.
AB  - The ciliary zonule, also known as Zinn's zonule, is composed of oxytalan fibers.
      However, the mechanism by which epithelial cells in the ciliary body form these
      fibers in not fully understood. We examined human nonpigmented ciliary epithelial
      cells to determine the appearance and amount of oxytalan fibers in terms of
      positivity for their major components, fibrillin-1 and fibrillin-2. Examination
      of fibrillin-1 and fibrillin-2 expression by immunofluorescence revealed that
      thin fibers positive for fibrillin-1 on Day 2 changed to thick fibers by Day 8.
      The fibers positive for fibrillin-2 appeared on the thick fibrillin-1-positive
      fibers after Day 4. Northern blot analysis revealed that the level of fibrillin-1
      did not change markedly, while induction of fibrillin-2 gene was evident on Day
      5. Western blot analysis showed that fibrillin-1 deposition increased gradually,
      while that of fibrillin-2 increased markedly from Day 5 to Day 8. Fibrillin-1
      suppression did not lead to the formation of fibrillin-2-positive thick fibers,
      whereas fibrillin-2 suppression led to the formation of fibrillin-1-positive thin
      fibers, but not thick fibers. These results suggest that both fibrillin-1 and
      fibrillin-2 are essential for the formation of thick oxytalan fibers in the
      ciliary zonule and are informative for clarifying the mechanism of homeostasis of
      the ocular matrix.

PMID- 21851252
TI  - Pericellular proteins of the developing mouse tendon: a proteomic analysis.
AB  - Tendon fibroblasts synthesize and assemble collagen fibrils, the basic structural
      unit of tendons. Regulation of fibrillogenesis is essential for tendon
      development and function. Fibril assembly begins within extracellular micro
      domains associated with the fibroblast surface. We hypothesize that molecules
      crucial to the regulation of fibril assembly are membrane associated and/or
      within the pericellular micro-environment. This report defines proteins in the
      surfaceome, that is, plasma membrane and pericellular matrix, from mouse flexor
      digitorum longus tendons. Proteomic analysis identified a set of surfaceome
      molecules including collagens, fibronectin, integrins, proteoglycans, and
      receptors in extracts from mouse tendons at postnatal day 1, a developmental
      stage when collagen protofibril nucleation and initial steps in fibril assembly
      predominate. The proteomic results were validated for molecules identified with a
      small number of unique peptides and/or low sequence coverage. For these analyses,
      proteins were selected based on their potential roles in fibril nucleation, that
      is, collagen V; organization of fibrillogenesis, that is, integrins and
      fibronectin; and known localization to the plasma membrane with potential to
      impact matrix assembly, that is, CD44, syndecan-1, epidermal growth factor
      receptor, and matrix metalloproteinase 25. These molecules were all detected in
      extracts of the developing tendon, demonstrating that the surfaceome included
      molecules hypothesized to regulate fibrillogenesis as well as many with no known
      function in this capacity. This report, therefore, generates an unbiased set of
      cell surface-associated molecules, providing a resource to identify novel or
      unexpected regulatory molecules involved in collagen fibril and matrix assembly.

PMID- 21851254
TI  - Association between CYP3A5 polymorphisms and blood pressure in kidney transplant
      recipients receiving calcineurin inhibitors.
AB  - Abstract   Renal cytochrome P450 3A5 (CYP3A5) has been associated with blood
      pressure (BP) control in humans. We investigated whether CYP3A5 polymorphisms are
      associated with post- transplant hypertension in a selected population of kidney
      recipients receiving calcineurin inhibitors.   Ninety-two kidney transplant
      recipients receiving cyclosporine (CyA) or tacrolimus (Tac) were genotyped for
      CYP3A5 polymorphisms, and the association between the CYP3A5 alleles (*1,*3) and
      hypertension on post-operative day (POD) 6 and POD 180 was verified, with
      multiple regression being used to identify the putative co-variates that may
      predict the extent and severity of hypertension in transplant recipients at
      different post-transplant times.   The CYP3A5*1 carriers had higher systolic
      (SBP) and diastolic blood pressure (DBP) in both the immediate and delayed post
      transplant period when adjusted for anti-hypertensive medication (POD 6: SBP =
      161 +/- 23 vs. 140 +/- 23 mmHg; DBP = 120 +/- 15 vs. 87 +/- 14 mmHg, p < 0.05.
      POD 180: SBP = 136 +/- 16 vs. 129 +/- 14 mmHg; DBP = 89 +/- 15 vs. 80 +/- 15
      mmHg, p < 0.05). The severity of hypertension between the CYP3A5*1 carriers and
      noncarriers on POD 6 was documented by the significantly different distribution
      of hypertension classes, but this was not confirmed on POD 180. The CYP3A5
      genotype was the only independent variable affecting mean arterial pressure.  
      The results of this study show that CYP3A5 polymorphisms are associated with the
      severity and degree of hypertension in kidney transplant recipients receiving
      calcineurin inhibitors regardless of the time of recording. However, the role of
      concomitant medications such as steroids with strong CYP3A5 inducing activity,
      should be taken into account.

PMID- 21851259
TI  - Editorial.

PMID- 21851256
TI  - Adhesive temperature: effects on adhesive properties and resin-dentin bond
      strength.
AB  - OBJECTIVES: To evaluate the effect of adhesive temperature on the resin-dentin
      bond strength (MUTBS), nanoleakage (NL), adhesive layer thickness (AL), and
      degree of conversion (DC) of ethanol/water- (SB) and acetone-based (PB) etch-and
      rinse adhesive systems. METHODS: The bottles of the two adhesives were kept at
      each temperature (5 degrees C, 20 degrees C, 37 degrees C, and 50 degrees C) for
      2 hours before application to demineralized dentin surfaces of 40 molars.
      Specimens were prepared for MUTBS testing. Bonded sticks (0.8 mm(2)) were tested
      under tension (0.5 mm/min). Three bonded sticks from each tooth were immersed in
      silver nitrate and analyzed by scanning electron microscopy. The DC of the
      adhesives was evaluated by Fourier transformed infrared spectroscopy. RESULTS:
      Lower MUTBS was observed for PB at 50 degrees C. For SB, the MUTBS values were
      similar for all temperatures. DC was higher at 50 degrees C for PB. Higher NL and
      thicker AL were observed for both adhesives in the 5 degrees C and 20 degrees C
      groups compared to the 37 degrees C and 50 degrees C groups. The higher
      temperatures (37 degrees C or 50 degrees C) reduced the number of pores within
      the adhesive layer of both adhesive systems. CONCLUSIONS: It could be useful to
      use an ethanol/water-based adhesive at 37 degrees C or 50 degrees C and an
      acetone-based adhesive at 37 degrees C to improve adhesive performance.

PMID- 21851260
TI  - Photoelastic analysis of cemented or screwed implant-supported prostheses with
      different prosthetic connections.
AB  - The aim of this study was to evaluate the stress distribution of different
      retention systems (screwed or cemented) associated with different prosthetic
      connections (external hexagon, internal hexagon, and Morse taper) in 3-unit
      implant-supported fixed partial dentures through photoelasticity. Six models were
      fabricated with photoelastic resin PL-2, and each model contained two implants of
      4.0 * 10.0 mm. The models presented different retention systems (screwed and
      cemented) and different connections (external hexagon, internal hexagon, and
      Morse taper). The prostheses were standardized and fabricated in Ni-Cr alloy. A
      circular polariscope was used and axial and oblique (45 degrees ) loads of 100 N
      were applied in a universal testing machine. The results were photographed and
      analyzed qualitatively with a graphic software (Adobe Photoshop). The screwed
      retention system exhibited higher number of fringes for both axial and oblique
      loadings. The internal hexagon implant presented better and lower stress
      distribution for both cemented and screwed prostheses. The oblique loading
      increased the number of fringes in all models tested. The cemented retention
      system presented better stress distribution. The internal hexagon implant was
      more favorable according to the biomechanical standpoint. The oblique load
      increased stress in all systems and connections tested.

PMID- 21851262
TI  - Severe hidradenitis suppurative in an HIV-positive male: use of multiple
      treatment modalities, including tumor necrosis factor blockade.

PMID- 21851264
TI  - Fluctuations in densities of the invasive gill parasite Centrocestus formosanus
      (Trematoda: Heterophyidae) in the Comal River, Comal County, Texas, U.S.A.
AB  - Centrocestus formosanus (Trematoda: Heterophyidae) is an invasive fish parasite
      in the Comal River, Texas, and is considered a threat to the federally endangered
      fountain darter, Etheostoma fonticola . Monitoring densities of C. formosanus
      cercariae is crucial to determining levels of infection pressure. We sampled 3
      sites in the Comal River during 2 sampling periods, the first during 2006-2007,
      and again during 2009-2010. Two of the sites were located in the upstream reach
      of Landa Lake, sites HS and LA, and the third site was located downstream of
      Landa Lake in the old channel of the river. Cercariae densities were highest at
      the downstream most site (EA), followed by sites LA and HS, during both sampling
      periods, but a significant decline in cercariae density was observed between the
      first and second sampling periods. Several abiotic factors were monitored,
      including total stream discharge, wading discharge, temperature, and dissolved
      oxygen, but no river-wide trends were observed. Therefore, we speculate that
      these factors do not adequately explain the observed long-term decline in
      cercariae density. We propose that the decline is simply a reflection of a
      typical pattern followed by most invasive species as they gradually become
      integrated into the local community following an initial explosive growth in
      population size. Although cercariae densities may be abating, fountain darters in
      the Comal River are still threatened by the parasite, and conservation efforts
      must focus on reducing levels of infection pressure from the parasite whenever
      possible.

PMID- 21851266
TI  - Our new "social" communication age in health.

PMID- 21851265
TI  - Impact of tenofovir versus abacavir on HIV-related endothelial dysfunction.

PMID- 21851267
TI  - Talk about "hooking up": the influence of college student social networks on
      nonrelationship sex.
AB  - This research considers how communication within college student social networks
      may encourage high-risk sexual relationships. Students (n = 274) described sexual
      scripts for hooking up and reported on peer communication, sexual behavior, and
      sexual attitudes. Students described varied hookup scripts, expressed ambivalent
      attitudes, and reported moderate participation in hookups overall. However, the
      most common hookup script, suggesting high-risk sexual activity (i.e., unplanned,
      inebriated sex), was featured in most accounts of students who themselves
      participated in hookups. Students overestimated how often others were hooking up,
      and these estimates were especially inflated by students who frequently talked
      about hooking up with friends. Among students with strong ties to peers, frequent
      peer communication about sex predicted participation in hookups and favorable
      attitudes about hooking up. Peer approval also predicted hookup behavior and
      attitudes.

PMID- 21851268
TI  - Immunomodulation and regeneration of islet Beta cells by cytokines in autoimmune
      type 1 diabetes.
AB  - Juvenile or type 1 diabetes (T1D) involves autoimmune-mediated destruction of
      insulin-producing beta cells in the islets of Langerhans in the pancreas. Lack of
      insulin prevents the absorption and metabolism of glucose throughout the body by
      interfering with cell signaling. Cytokines have been shown to play a key role in
      beta cell destruction and regulation of autoimmunity in T1D. The multiple roles
      of cytokines in T1D pathogenesis, regulation, and regeneration of beta cells
      presents both promise and challenge for their use in immunotherapy. We found that
      mycobacterial adjuvants induce various regulatory T cells in the non-obese
      diabetic (NOD) mouse model of T1D. Cytokines produced by these cells not only
      regulate innate and adaptive immunity but also prevent the development of
      diabetes and partially restored normoglycemia in diabetic NOD mice. We discovered
      that adjuvant immunotherapy upregulated Regenerating (Reg) genes in the islets
      and induced interleukin 22 (IL-22)-producing Th17 cells. IL-22 is known to
      upregulate Reg gene expression in islets and could potentially induce
      regeneration of beta cells and prevent their apoptosis. Therefore, cytokines both
      induce and regulate T1D and have the potential to regenerate and preserve insulin
      producing beta cells in the islets.

PMID- 21851270
TI  - Does nephrometry scoring of renal tumors predict outcomes in patients selected
      for robot-assisted partial nephrectomy?
AB  - BACKGROUND AND PURPOSE: Robot-assisted partial nephrectomy has emerged as a
      viable surgical treatment for patients with certain renal tumors. We hypothesized
      that extirpation of more complex tumors, as graded with the nephrometry score,
      would result in worse operative and postoperative outcomes when compared with
      tumors with lower nephrometry scores. We report whether nephrometry-graded tumor
      complexity impacted operative or postoperative outcomes. PATIENTS AND METHODS: A
      single experienced surgeon at our tertiary-care institution performed more than
      100 robot-assisted partial nephrectomies. Istitutional Review Board-approved data
      collection was available for 95 patients, and nephrometry scores were available
      for 92 patients. Cases were divided into tertiles, based on their nephrometry
      score of low, medium, or high. We compared preoperative, operative, and
      postoperative data to evaluate any differences between the three tertiles.
      Statistical analysis was performed using JMP 8 software. RESULTS: There were 66,
      22, and 4 patients in the low, medium, and high nephrometry score tertiles,
      respectively. There were no statistically significant differences between the
      tertiles regarding warm ischemia time, estimated blood loss, operative time,
      length of stay, change in glomerular filtration rate, Clavien-graded complication
      rates, or any other metric. Mean follow-up for each tertile was also similar.
      CONCLUSIONS: We have routinely been using the nephrometry scoring system to
      anatomically describe renal masses before robot-assisted partial nephrectomy. Our
      findings demonstrate that nephrometry-graded tumor complexity was not related to
      any differences in outcomes for patients with renal tumors who were selected at
      our institution to undergo robot-assisted partial nephrectomy. The nephrometry
      system remains a reproducible standardized classification of renal tumor anatomy,
      but it remains to be seen if this can be used to predict surgical outcomes.

PMID- 21851269
TI  - Collagen-calcium phosphate cement scaffolds seeded with umbilical cord stem cells
      for bone tissue engineering.
AB  - Human umbilical cord mesenchymal stem cells (hUCMSCs) avoid the invasive
      procedure required to harvest bone marrow MSCs. The addition of collagen fibers
      into self-setting calcium phosphate cement (CPC) may increase the scaffold
      strength, and enhance cell attachment and differentiation. The objectives of this
      study were to develop a novel class of collagen-CPC composite scaffolds, and to
      investigate hUCMSC attachment, proliferation, and osteogenic differentiation on
      collagen-CPC scaffolds for the first time. Collagen fibers in CPC improved the
      load-bearing capability. Flow cytometry showed that the hUCMSCs expressed cell
      surface markers characteristic of MSCs, and were negative for hematopoietic and
      endothelial cell markers. hUCMSCs proliferated rapidly in all CPC composite
      scaffolds, with cell number increasing by sevenfold in 8 days. Cellular function
      was enhanced with collagen fibers in CPC scaffolds. Cell density increased from
      (645+/-60) cells/mm(2) on CPC with 0% collagen, to (1056+/-65) cells/mm(2) on CPC
      with 8% collagen (p<0.05). The actin stress fibers inside the hUCMSCs were
      stained, and the fluorescence intensity was doubled when the collagen in CPC was
      increased by 0% to 8%. RT-PCR showed that hUCMSCs on CPC with collagen had higher
      osteogenic expression than those on CPC without collagen. Alizarin Red S staining
      revealed a great increase in mineralization by hUCMSCs on CPC with collagen than
      that without collagen. In conclusion, hUCMSCs showed excellent proliferation,
      differentiation, and synthesis of bone minerals in collagen-CPC composite
      scaffolds for the first time. The novel hUCMSC-seeded collagen-CPC construct with
      superior cell function and load-bearing capability is promising to enhance bone
      regeneration in a wide range of orthopedic and craniofacial applications.

PMID- 21851271
TI  - Percutaneous nephrolithotomy of caliceal diverticular calculi: a single center
      experience.
AB  - BACKGROUND AND PURPOSE: Caliceal diverticula are rare renal anomalies present in
      approximately 0.6% of the population. They are associated with calculi in 50% of
      cases. Therapeutic options include several minimally invasive techniques. We
      report a retrospective review of outcomes and complications from our series of
      patients who were treated with a percutaneous approach. PATIENTS AND METHODS: A
      database of outcomes related to percutaneous nephrolithotomy (PCNL) has been
      maintained at our institution since 1992. Data on all patients with caliceal
      diverticular stones who underwent PCNL during a 17-year period from 1992 to 2009
      were reviewed retrospectively. Our preferred approach to PCNL in these patients
      is to puncture directly into the diverticulum and to try to advance a guidewire
      through the infundibular neck. In cases where the caliceal neck could not be
      intubated, we performed a transdiverticular approach with creation of a
      neoinfundibulum as a salvage procedure. We evaluated the two techniques with
      regard to stone-free rates and early postoperative complications. RESULTS:
      Seventy-six procedures were performed. The mean age was 43 years (range 17-72 y).
      The mean stone area was 583 mm(2). The surgical approach was direct puncture in
      47, transdiverticular in 20, retrograde in 8, and unknown in 1 patient. Eight
      patients underwent lining fulguration. The average duration of surgery was 75
      minutes (23-169 min) with an average hospital stay of 4.7 days. There were a
      total of 23 complications, of which 11 necessitated additional intervention. The
      overall stone-free rates were 77% and 89% for direct puncture and
      transdiverticular approaches, respectively. CONCLUSIONS: The percutaneous
      management of caliceal diverticular calculi is highly effective and can be
      accomplished with low morbidity.

PMID- 21851272
TI  - Computed tomography-urography for upper urinary tract imaging: is it required for
      all patients who present with hematuria?
AB  - PURPOSE: To define in which patients who present with microscopic or macroscopic
      hematuria CT urography (CTU) is indicated as an imaging mode for the upper
      urinary tract (UUT). PATIENTS AND METHODS: We conducted a prospective study on
      consecutive patients who attended a modern protocol-driven hematuria clinic from
      January 2006 to February 2010. Standard tests (history taking, physical
      examination, urinalysis via dipstick method, ultrasonography of kidneys and
      bladder performed by urologists, cystoscopy, and cytology) were directed to all
      patients, whereas the mode of additional UUT imaging (ultrasonography by a
      radiologist or four-phase CTU/magnetic resonance (MR) urography (MRU) when CTU
      was contraindicated) was selected according to a risk factor-based management
      algorithm. The added value of cross-sectional urography (CTU/MRU) supplementary
      to ultrasonography (by urologists) to detect renal masses, UUT tumors, and stones
      was assessed. Univariate and multivariate analysis on predictive factors for
      cross-sectional urography result were performed. RESULTS: From the total of 841
      patients, lesions that might account for hematuria could not be identified in 462
      (54.9%), whereas in 250 (29.7%) and 124 (14.7%) patients, hematuria was from
      benign and malignant disease, respectively. Cross-sectional urography revealed
      relevant UUT lesions in 73 of 525 (13.9%) patients. Only result of
      ultrasonography (odds ratio [OR] 7.7, 95% confidence interval [CI] 4.0-14.9),
      P<0.001) and type of hematuria (OR 2.6, 95% CI 1.3-5.1, P=0.01) were significant
      predictors for cross-sectional urography result. In 44 of 456 (9.6%) patients
      with no abnormalities on ultrasonography, CTU/MRU revealed that these were false
      negatives, with most lesions missed being stones. In 253 of 309 (81.9%) patients
      with macroscopic hematuria, no lesions were detected in the UUT on CTU/MRU, in
      contrast to 199 of 216 patients (92.1%) with microscopic hematuria. CONCLUSION:
      For patients who present with microscopic hematuria, ultrasonography is
      sufficient to exclude significant UUT disease. For patients with macroscopic
      hematuria, the likelihood of finding UUT disease is higher, and a CTU as a first
      line test seems justified.

PMID- 21851273
TI  - Molecular genetics external quality assessment pilot scheme for KRAS analysis in
      metastatic colorectal cancer.
AB  - Laboratories are increasingly required to perform molecular tests for the
      detection of mutations in the KRAS gene in metastatic colorectal cancers to allow
      better clinical management and more effective treatment for these patients. KRAS
      mutation status predicts a patient's likely response to the monoclonal antibody
      cetuximab. To provide a high standard of service, these laboratories require
      external quality assessment (EQA) to monitor the level of laboratory output and
      measure the performance of the laboratory against other service providers.
      National External Quality Assurance Services for Molecular Genetics provided a
      pilot EQA scheme for KRAS molecular analysis in metastatic colorectal cancers
      during 2009. Very few genotyping errors were reported by participating
      laboratories; however, the reporting nomenclature of the genotyping results
      varied considerably between laboratories. The pilot EQA scheme highlighted the
      need for continuing EQA in this field which will assess the laboratories' ability
      not only to obtain accurate, reliable results but also to interpret them safely
      and correctly ensuring that the referring clinician has the correct information
      to make the best clinical therapeutic decision for their patient.

PMID- 21851274
TI  - Geometry-invariant texture retrieval using a dual-output pulse-coupled neural
      network.
AB  - This letter proposes a novel dual-output pulse coupled neural network model
      (DPCNN). The new model is applied to obtain a more stable texture description in
      the face of the geometric transformation. Time series, which are computed from
      output binary images of DPCNN, are employed as translation-, rotation-, scale-,
      and distortion-invariant texture features. In the experiments, DPCNN has been
      well tested by using Brodatz's album and the VisTex database. Several existing
      models are compared with the proposed DPCNN model. The experimental results,
      based on different testing data sets for images with different translations,
      orientations, scales, and affine transformations, show that our proposed model
      outperforms existing models in geometry-invariant texture retrieval. Furthermore,
      the robustness of DPCNN to noisy data is examined in the experiments.

PMID- 21851275
TI  - Self-organization of topographic bilinear networks for invariant recognition.
AB  - We present a model for the emergence of ordered fiber projections that may serve
      as a basis for invariant recognition. After invariance transformations are self
      organized, so-called control units competitively activate fiber projections for
      different transformation parameters. The model builds on a well-known ontogenetic
      mechanism, activity-based development of retinotopy, and it employs activity
      blobs of varying position and size to install different transformations. We
      provide a detailed analysis for the case of 1D input and output fields for
      schematic input patterns that shows how the model is able to develop specific
      mappings. We discuss results that show that the proposed learning scheme is
      stable for complex, biologically more realistic input patterns. Finally, we show
      that the model generalizes to 2D neuronal fields driven by simulated retinal
      waves.

PMID- 21851276
TI  - A spline framework for estimating the EEG surface laplacian using the Euclidean
      metric.
AB  - This letter develops a framework for EEG analysis and similar applications based
      on polyharmonic splines. This development overcomes a basic problem with the
      method of splines in the Euclidean setting: that it does not work on low-degree
      algebraic surfaces such as spherical and ellipsoidal scalp models. The method's
      capability is illustrated through simulations on the three-sphere model and using
      empirical data.

PMID- 21851277
TI  - A model of motion transparency processing with local center-surround interactions
      and feedback.
AB  - Motion transparency occurs when multiple coherent motions are perceived in one
      spatial location. Imagine, for instance, looking out of the window of a bus on a
      bright day, where the world outside the window is passing by and movements of
      passengers inside the bus are reflected in the window. The overlay of both
      motions at the window leads to motion transparency, which is challenging to
      process.   Noisy and ambiguous motion signals can be reduced using a competition
      mechanism for all encoded motions in one spatial location. Such a competition,
      however, leads to the suppression of multiple peak responses that encode
      different motions, as only the strongest response tends to survive. As a
      solution, we suggest a local center-surround competition for population-encoded
      motion directions and speeds. Similar motions are supported, and dissimilar ones
      are separated, by representing them as multiple activations, which occurs in the
      case of motion transparency. Psychophysical findings, such as motion attraction
      and repulsion for motion transparency displays, can be explained by this local
      competition.   Besides this local competition mechanism, we show that feedback
      signals improve the processing of motion transparency. A discrimination task for
      transparent versus opaque motion is simulated, where motion transparency is
      generated by superimposing large field motion patterns of either varying size or
      varying coherence of motion. The model's perceptual thresholds with and without
      feedback are calculated. We demonstrate that initially weak peak responses can be
      enhanced and stabilized through modulatory feedback signals from higher stages of
      processing.

PMID- 21851278
TI  - Recurrent kernel machines: computing with infinite echo state networks.
AB  - Echo state networks (ESNs) are large, random recurrent neural networks with a
      single trained linear readout layer. Despite the untrained nature of the
      recurrent weights, they are capable of performing universal computations on
      temporal input data, which makes them interesting for both theoretical research
      and practical applications. The key to their success lies in the fact that the
      network computes a broad set of nonlinear, spatiotemporal mappings of the input
      data, on which linear regression or classification can easily be performed. One
      could consider the reservoir as a spatiotemporal kernel, in which the mapping to
      a high-dimensional space is computed explicitly. In this letter, we build on this
      idea and extend the concept of ESNs to infinite-sized recurrent neural networks,
      which can be considered recursive kernels that subsequently can be used to create
      recursive support vector machines. We present the theoretical framework, provide
      several practical examples of recursive kernels, and apply them to typical
      temporal tasks.

PMID- 21851279
TI  - Guaranteed cost synchronization of chaotic cellular neural networks with time
      varying delay.
AB  - Synchronization of cellular neural networks with time-varying delay is discussed
      in this letter. Based on Razumikhin theorem, a guaranteed cost synchronous
      controller is given. Unlike Lyapunov-Krasovskii analysis process, there is no
      constraint on the change rate of time delay. The saturated terms emerging in the
      Razumikhin analysis are amplified by zoned discussion and maximax synthesis
      rather than by Lipschitz condition and vector inequality, which will bring more
      conservatism. Then the controller criterion is transformed from quadratic matrix
      inequality form into linear matrix inequality form, with the help of a sufficient
      and necessary transformation condition. The minimization of the guaranteed cost
      is studied, and a further criterion for getting the controller is presented.
      Finally, the guaranteed cost synchronous control and its corresponding
      minimization problem are illustrated with examples of chaotic time-varying delay
      cellular neural networks.

PMID- 21851280
TI  - Computing confidence intervals for point process models.
AB  - Characterizing neural spiking activity as a function of intrinsic and extrinsic
      factors is important in neuroscience. Point process models are valuable for
      capturing such information; however, the process of fully applying these models
      is not always obvious. A complete model application has four broad steps:
      specification of the model, estimation of model parameters given observed data,
      verification of the model using goodness of fit, and characterization of the
      model using confidence bounds. Of these steps, only the first three have been
      applied widely in the literature, suggesting the need to dedicate a discussion to
      how the time-rescaling theorem, in combination with parametric bootstrap
      sampling, can be generally used to compute confidence bounds of point process
      models. In our first example, we use a generalized linear model of spiking
      propensity to demonstrate that confidence bounds derived from bootstrap
      simulations are consistent with those computed from closed-form analytic
      solutions. In our second example, we consider an adaptive point process model of
      hippocampal place field plasticity for which no analytical confidence bounds can
      be derived. We demonstrate how to simulate bootstrap samples from adaptive point
      process models, how to use these samples to generate confidence bounds, and how
      to statistically test the hypothesis that neural representations at two time
      points are significantly different. These examples have been designed as useful
      guides for performing scientific inference based on point process models.

PMID- 21851281
TI  - Reward-weighted regression with sample reuse for direct policy search in
      reinforcement learning.
AB  - Direct policy search is a promising reinforcement learning framework, in
      particular for controlling continuous, high-dimensional systems. Policy search
      often requires a large number of samples for obtaining a stable policy update
      estimator, and this is prohibitive when the sampling cost is expensive. In this
      letter, we extend an expectation-maximization-based policy search method so that
      previously collected samples can be efficiently reused. The usefulness of the
      proposed method, reward-weighted regression with sample reuse (R3), is
      demonstrated through robot learning experiments. (This letter is an extended
      version of our earlier conference paper: Hachiya, Peters, & Sugiyama, 2009 .).

PMID- 21851282
TI  - Estimating parameters of generalized integrate-and-fire neurons from the maximum
      likelihood of spike trains.
AB  - When a neuronal spike train is observed, what can we deduce from it about the
      properties of the neuron that generated it? A natural way to answer this question
      is to make an assumption about the type of neuron, select an appropriate model
      for this type, and then choose the model parameters as those that are most likely
      to generate the observed spike train. This is the maximum likelihood method. If
      the neuron obeys simple integrate-and-fire dynamics, Paninski, Pillow, and
      Simoncelli (2004) showed that its negative log-likelihood function is convex and
      that, at least in principle, its unique global minimum can thus be found by
      gradient descent techniques. Many biological neurons are, however, known to
      generate a richer repertoire of spiking behaviors than can be explained in a
      simple integrate-and-fire model. For instance, such a model retains only an
      implicit (through spike-induced currents), not an explicit, memory of its input;
      an example of a physiological situation that cannot be explained is the absence
      of firing if the input current is increased very slowly. Therefore, we use an
      expanded model (Mihalas & Niebur, 2009 ), which is capable of generating a large
      number of complex firing patterns while still being linear. Linearity is
      important because it maintains the distribution of the random variables and still
      allows maximum likelihood methods to be used. In this study, we show that
      although convexity of the negative log-likelihood function is not guaranteed for
      this model, the minimum of this function yields a good estimate for the model
      parameters, in particular if the noise level is treated as a free parameter.
      Furthermore, we show that a nonlinear function minimization method (r-algorithm
      with space dilation) usually reaches the global minimum.

PMID- 21851283
TI  - Dependency reduction with divisive normalization: justification and
      effectiveness.
AB  - Efficient coding transforms that reduce or remove statistical dependencies in
      natural sensory signals are important for both biology and engineering. In recent
      years, divisive normalization (DN) has been advocated as a simple and effective
      nonlinear efficient coding transform. In this work, we first elaborate on the
      theoretical justification for DN as an efficient coding transform. Specifically,
      we use the multivariate t model to represent several important statistical
      properties of natural sensory signals and show that DN approximates the optimal
      transforms that eliminate statistical dependencies in the multivariate t model.
      Second, we show that several forms of DN used in the literature are equivalent in
      their effects as efficient coding transforms. Third, we provide a quantitative
      evaluation of the overall dependency reduction performance of DN for both the
      multivariate t models and natural sensory signals. Finally, we find that
      statistical dependencies in the multivariate t model and natural sensory signals
      are increased by the DN transform with low-input dimensions. This implies that
      for DN to be an effective efficient coding transform, it has to pool over a
      sufficiently large number of inputs.

PMID- 21851284
TI  - Assessment of scar quality after cleft lip closure.
AB  - OBJECTIVE: To assess scar quality after cleft lip repair. DESIGN: The linear
      scars of patients with cleft lip with or without cleft palate were evaluated in a
      prospective study using the Patient and Observer Scar Assessment Scale. Linear
      regression was performed to identify which scar characteristics were important
      according to patients and observer. SETTING: Regular outpatient follow-up visit
      with the cleft palate teams of two tertiary centers. PATIENTS: All consecutive
      patients were asked to participate in this study after informed consent,
      minimally 1 year postsurgery. MAIN OUTCOME MEASURE: Scar characteristics
      influencing patient and observer opinion after cleft lip repair. RESULTS: A total
      of 86 patients with cleft lip with or without cleft palate were included,
      resulting in evaluation of 99 scars. Two scar characteristics, itching and pain,
      were seldom a concern for the patients. Linear regression showed that scars
      assessed longer after surgery had a better outcome. CONCLUSION: Scar itching and
      pain did not seem to have an effect on patient opinion of the quality of the
      scar, and the majority of the patients were more satisfied with the outcome of
      their scar than the observer was.

PMID- 21851285
TI  - Assessment of volumetric changes with a best-fit method in three-dimensional
      stereophotograms.
AB  - OBJECTIVE: Different three-dimensional stereophotogrammetry systems and analyzing
      methods exist that often use landmarks for comparison. Measurement errors in
      landmark or surface comparison are mostly within 1 mm, which seems clinically
      acceptable. The aim of this study was to validate a three-dimensional
      stereophotogrammetric best-fit method of assessing volumetric changes and to
      compare three devices. METHODS: The validation of the best-fit method was at
      first done on a life-size dummy head. Scans were made in the ideal position, as
      well as in four additional positions, and a scan was made in which a soft putty
      specimen was added to the dummy head. The comparison was executed with a best-fit
      method using triangulation. Student's t tests were used to detect statistically
      significant differences. Second, comparisons were made among scans of a white man
      in the ideal position and with volume changes added. RESULTS: The different
      positions tested for the dummy head showed no significant volume differences
      within each system or among systems. The differences found when adding a soft
      putty specimen fell into the same range as the differences between various
      positions. The differences within a live situation were 10 times greater compared
      with the dummy-head situation. CONCLUSIONS: In a dummy-head situation, the
      different systems gave similar results when tested with a best-fit method.
      However, in live situations the differences may become 10 times greater, possibly
      due to different facial expressions. These differences may become clinically
      relevant and, therefore, further research in volumetric changes is needed.

PMID- 21851286
TI  - Insulin modulates glucose-dependent insulinotropic polypeptide (GIP) secretion
      from enteroendocrine K cells in rats.
AB  - Effects of insulin excess and deficiency on glucose-dependent insulinotropic
      polypeptide (GIP) was examined in rats following insulinoma transplantation or
      streptozotocin (STZ) administration. Over 14 days, food intake was increased (p <
      0.001) in both groups of rats, with decreased body weight (p < 0.01) in STZ rats.
      Non-fasting plasma glucose levels were decreased (p < 0.01) and plasma insulin
      levels increased (p < 0.001) in insulinoma-bearing rats, whereas STZ treatment
      elevated glucose (p < 0.001) and decreased insulin (p < 0.01). Circulating GIP
      concentrations were elevated (p < 0.01) in both animal models. At 14 days, oral
      glucose resulted in a decreased glycaemic excursion (p < 0.05) with concomitant
      elevations in insulin release (p < 0.001) in insulinoma-bearing rats, whereas STZ
      treated rats displayed similar glucose-lowering effects but reduced insulin
      levels (p < 0.01). GIP concentrations were augmented in STZ rats (p < 0.05)
      following oral glucose. Plasma glucose and insulin concentrations were not
      affected by oral fat, but fat-induced GIP secretion was particularly (p < 0.05)
      increased in insulinoma-bearing rats. Exogenous GIP enhanced (p < 0.05) glucose
      lowering in all groups of rats accompanied by insulin releasing (p < 0.001)
      effects in insulinoma-bearing and control rats. Both rat models exhibited
      increased (p < 0.001) intestinal weight but decreased intestinal GIP
      concentrations. These data suggest that circulating insulin has direct and
      indirect effects on the synthesis and secretion of GIP.

PMID- 21851288
TI  - Assistive technology use is associated with reduced capability poverty: a cross
      sectional study in Bangladesh.
AB  - PURPOSE: About half of all people with disabilities in developing countries live
      in extreme poverty. Focusing on the ends rather than the economic means of human
      development, the capability approach offers an alternative view of poverty. The
      purpose of this study was to explore the relation between assistive technology
      use and capability poverty in a low-income country. METHOD: Self-reported data on
      food intake, health care, education, politics, self-determination, self-respect,
      family relationships and friendships were collected in Bangladesh through
      interviews of people with hearing impairments using and not using hearings aids,
      and people with ambulatory impairments using and not using manual wheelchairs (N
      = 583). Differences in outcomes between users and non-users of assistive
      technology were analyzed using logistic regression. RESULTS: Assistive technology
      users were more likely than non-users to report enhanced capabilities, hearing
      aid users to a larger extent than wheelchair users. Synergistic effects between
      assistive technology use and education were found. CONCLUSION: The use of
      assistive technology is predictive of reduced capability poverty in Bangladesh.
      Lack of wheelchair accessibility and the nature of selected outcomes may explain
      the limited association in the ambulatory group. Enhancing the effects of the
      other, there is support for providing education in combination with hearing aids.
      [Box: see text].

PMID- 21851289
TI  - Preparation and pharmacokinetics in beagle dogs of once-a-day tetramethylpyrazine
      phosphate sustained-release pellets.
AB  - In this study, once-a-day tetramethylpyrazine phosphate (TMPP) sustained-release
      pellets were successfully prepared. The pellets cores were carried out in
      extrusion-spheronization machine and then coated in fluidized-bed. To optimize
      cumulative release profile, two different coating systems with the same the TMPP
      pellets cores were employed. The first coating system consisted of surlease,
      containing HPMC E5 (0.1% w/w), i.e., P1. The second coating system only consisted
      of surlease, i.e., P2. The two kinds of coating systems were both given coating
      levels in terms of weight gain of 10%. The resulted once-a-day TMPP sustained
      release pellets (OTSP), the mixture of P1 and P2 with the weight proportion of
      1:1, were filled in a capsule (150 mg TMPP/capsule). The relative bioavailability
      of OTSP was studied in six beagle dogs after oral administration using a
      commercial TMPP tablets as a reference. The C(max) and T(max) for OTSP and TMPP
      tablets were 213.06 ng/mL, 2.50 h and 3402.13 ng/mL, 0.33 h, respectively and the
      relative bioavailability of P3 was 97.18% compared with TMPP tablets. Based on
      the results, it was indicated that TMPP sustained-release pellets and TMPP
      conventional tablets were bioequivalent.

PMID- 21851287
TI  - Targeting Mcl-1 for the therapy of cancer.
AB  - INTRODUCTION: Human cancers are genetically and epigenetically heterogeneous and
      have the capacity to commandeer a variety of cellular processes to aid in their
      survival, growth and resistance to therapy. One strategy is to overexpress
      proteins that suppress apoptosis, such as the Bcl-2 family protein Mcl-1. The Mcl
      1 protein plays a pivotal role in protecting cells from apoptosis and is
      overexpressed in a variety of human cancers. AREAS COVERED: Targeting Mcl-1 for
      extinction in these cancers, using genetic and pharmacological approaches,
      represents a potentially effectual means of developing new efficacious cancer
      therapeutics. Here we review the multiple strategies that have been employed in
      targeting this fundamental protein, as well as the significant potential these
      targeting agents provide in not only suppressing cancer growth, but also in
      reversing resistance to conventional cancer treatments. EXPERT OPINION: We
      discuss the potential issues that arise in targeting Mcl-1 and other Bcl-2 anti
      apoptotic proteins, as well problems with acquired resistance. The application of
      combinatorial approaches that involve inhibiting Mcl-1 and manipulation of
      additional signaling pathways to enhance therapeutic outcomes is also
      highlighted. The ability to specifically inhibit key genetic/epigenetic elements
      and biochemical pathways that maintain the tumor state represent a viable
      approach for developing rationally based, effective cancer therapies.

PMID- 21851290
TI  - Associations between size-segregated particle number concentrations and
      respiratory mortality in Beijing, China.
AB  - Numerous studies have described the adverse associations between particle mass
      and respiratory health. The aim of the study was to analyze the associations of
      particle properties, especially size-segregated particle number concentrations
      (PNC), and respiratory mortality in Beijing, P.R. China. We gathered daily values
      of respiratory mortality and air pollution data of the Beijing urban area.
      Generalized additive models were used to estimate the associations. Single
      pollutant models showed that delayed concentrations of SO(2), total PNCs, and PNC
      of 300-1000 nm were adversely associated with total respiratory mortality. There
      was an indication that adverse health effects of PNCs might be stronger for
      stagnant air masses. Two-pollutant models verified the independence of
      associations of total PNCs of other pollutants (SO(2), NO(2), and PM(10)). In
      conclusion, particle number concentrations, especially accumulation mode
      particles, might be factors influencing the adverse associations between
      particulate matter and respiratory health.

PMID- 21851291
TI  - Psychosocial work characteristics, need for recovery and musculoskeletal problems
      predict psychological distress in a sample of British workers.
AB  - From an original sample of 2454 participants free of self-reported psychological
      distress, 1463 workers completed a 15-month follow-up. Baseline measures included
      exposure to job demands, decision latitude, social support and need for recovery.
      Psychological distress was assessed using the General Health Questionnaire at
      baseline and at follow-up. The findings showed that medium and high exposure to
      job demands and social support increased the risk of reporting psychological
      distress at 15-months (relative risk (RR) = 1.65, 1.45). The highest adjusted RR
      was observed for workers reporting a high need for recovery after work (RR 2.12,
      1.90) and this finding was independent of the effects of job demands, decision
      latitude and social support. Neither decision latitude, nor low back problems
      increased the risk of reporting future psychological distress, although neck
      problems (RR = 1.66) and hand/wrist problems (RR = 1.45) did. It was concluded
      that need for recovery appears to be an important indicator of individual workers
      who are at risk of developing psychological distress long term. STATEMENT OF
      RELEVANCE: This paper reports the findings of a longitudinal study showing that
      need for recovery from work was the strongest predictor, relative to psychosocial
      work characteristics (job demands, decision latitude and social support), and
      musculoskeletal problems, of psychological distress 15 months later in
      individuals initially free from distress.

PMID- 21851292
TI  - Gender and walking speed effects on plantar pressure distribution for adults aged
      20-60 years.
AB  - This study investigates gender and walking speed (80%, 100%, 120% and 140% of
      preferred walking speed (PWS)) effects on plantar pressure parameters. In total,
      30 healthy males and females, aged between 20 to 60 years, participated in this
      study. A plantar pressure measurement device was used to measure the peak
      pressure, peak force and contact area in six plantar zones. The results indicate
      that males had higher peak pressure and peak force in the medial toe and
      forefoot, as well as greater contact area in the central forefoot and heel areas.
      Females had greater contact area in the midfoot. Increased walking speed caused a
      significant increase in most of the response measures and the increase became
      more obvious when the speed was higher than 120% PWS. Although there was no
      significant interaction between gender and PWS, some gender differences were
      found. PRACTITIONER SUMMARY: Using percentage PWS provides a new perspective to
      discuss the effects of gender and walking speed on plantar pressure distribution.
      This study's findings can be very useful for footwear and orthotics design for
      different genders.

PMID- 21851293
TI  - Effect of treatment environment on modified constraint-induced movement therapy
      results in children with spastic hemiplegic cerebral palsy: a randomized
      controlled trial.
AB  - PURPOSE: To determine the effects of treatment environment (home and clinic) on
      results of modified constraint-induced movement therapy (modified CIMT) in
      children with spastic hemiplegic cerebral palsy. METHOD: In a single-blinded,
      randomized, controlled trial, 14 children with spastic hemiplegic cerebral palsy
      (5 females, 9 males; mean age: 74 months) received 15 hours of modified CIMT,
      occurring three times/week for 10 sessions every other day in two randomly
      assigned groups. Each session lasts one and half hours. Treatment environment for
      intervention group (n = 7) was home and for control group (n = 7) was clinic.
      Measures were conducted pre, post and 3 months after treatment period by
      pediatrics motor activity log and subtests 5 (upper limb coordination) and 8
      (upper limb speed and dexterity) of Bruininks-Oseretsky test of motor
      proficiency. Sample randomization and data analysis by analysis of variance with
      repeated measures were conducted by SPSS-16 software in alpha level set at p <
      0.05. RESULTS: All subjects showed significant improvement (p < 0.01) in post
      test measures except subtest 5 of Bruininks-Oseretsky test of motor proficiency.
      In contrast to clinic group, subjects in home showed significantly continued
      improvement at follow-up session in all measures. CONCLUSIONS: Modified CIMT is
      effective in improving upper limb function in children with spastic hemiplegic
      cerebral palsy. In addition, more improved performance in home group places the
      practice in natural context as the preferred method for treatment of these
      children.

PMID- 21851294
TI  - Evaluating the process parameters of the dry coating process using a 2(5-1)
      factorial design.
AB  - CONTEXT: A recent development of coating technology is dry coating, where polymer
      powder and liquid plasticizer are layered on the cores without using organic
      solvents or water. Several studies evaluating the process were introduced in
      literature, however, little information about the critical process parameters
      (CPPs) is given. AIM: Aim of the study was the investigation and optimization of
      CPPs with respect to one of the critical quality attributes (CQAs), the coating
      efficiency of the dry coating process in a rotary fluid bed. MATERIALS AND
      METHODS: Theophylline pellets were coated with hydroxypropyl methylcellulose
      acetate succinate as enteric film former and triethyl citrate and acetylated
      monoglyceride as plasticizer. A 2(5-1) design of experiments (DOEs) was created
      investigating five independent process parameters namely coating temperature,
      curing temperature, feeding/spraying rate, air flow and rotor speed. The results
      were evaluated by multilinear regression using the software Modde((r)) 7. RESULTS
      AND DISCUSSION: It is shown, that generally, low feeding/spraying rates and low
      rotor speeds increase coating efficiency. High coating temperatures enhance
      coating efficiency, whereas medium curing temperatures have been found to be
      optimum in terms of coating efficiency. CONCLUSION: This study provides a
      scientific base for the design of efficient dry coating processes with respect to
      coating efficiency.

PMID- 21851296
TI  - Combined approach to demonstrate acetylcholinesterase activity changes in the rat
      brain following tabun intoxication and its treatment.
AB  - Reactivation effects of K203 and currently available oximes (obidoxime, HI-6) in
      combination with atropine on acetylcholinesterase activities in the brain parts
      of rats poisoned with tabun were studied. The activity was determined by
      quantitative histochemical and biochemical methods correlating between them very
      well. The tabun-induced changes in acetylcholinsterase activity as well as in
      reactivation potency of reactivators used were different in various parts of the
      brain. Pontomedullar area seems to be important for observed changes following
      tabun intoxication and its treatment. From the oximes studied, the reactivation
      effect of K203 was comparable with obidoxime; HI-6 was ineffective. Combination
      of bio- and histochemical methods allow fine differentiation among the action of
      different oximes following tabun poisoning.

PMID- 21851295
TI  - Lipotoxicity and cardiac dysfunction in mammals and Drosophila.
AB  - The lipotoxic effects of obesity are important contributing factors in cancer,
      diabetes, and cardiovascular disease (CVD), but the genetic mechanisms, by which
      lipotoxicity influences the initiation and progression of CVD are poorly
      understood. Hearts, of obese and diabetic individuals, exhibit several phenotypes
      in common, including ventricular remodeling, prolonged QT intervals, enhanced
      frequency of diastolic and/or systolic dysfunction, and decreased fractional
      shortening. High systemic lipid concentrations are thought to be the leading
      cause of lipid-related CVD in obese or diabetic individuals. However, an
      alternative possibility is that obesity leads to cardiac-specific steatosis, in
      which lipids and their metabolites accumulate within the myocardial cells
      themselves and thereby disrupt normal cardiovascular function. Drosophila has
      recently emerged as an excellent model to study the fundamental genetic
      mechanisms of metabolic control, as well as their relationship to heart function.
      Two recent studies of genetic and diet-induced cardiac lipotoxicity illustrate
      this. One study found that alterations in genes associated with membrane
      phospholipid metabolism may play a role in the abnormal lipid accumulation
      associated with cardiomyopathies. The second study showed that Drosophila fed a
      diet high in saturated fats, developed obesity, dysregulated insulin and glucose
      homeostasis, and severe cardiac dysfunction. Here, we review the current
      understanding of the mechanisms that contribute to the detrimental effects of
      dysregulated lipid metabolism on cardiovascular function. We also discuss how the
      Drosophila model could help elucidate the basic genetic mechanisms of
      lipotoxicity- and metabolic syndrome-related cardiomyopathies in mammals.

PMID- 21851297
TI  - Longevity of Mycobacterium bovis in brushtail possum (Trichosurus vulpecula)
      carcasses, and contact rates between possums and carcasses.
AB  - AIM: To determine, for a variety of environmental conditions, how long
      Mycobacterium bovis might remain viable inside the carcass of a brushtail possum
      (Trichosurus vulpecula) that died of bovine tuberculosis (Tb), and to measure the
      rate of contact between free-ranging possums and possum carcasses. METHODS:
      Lesions of M. bovis were simulated by inoculating excised spleens weighing 0.5-1
      g with 0.2 mL liquid culture containing approximately 5 x 10(7) cfu M. bovis/mL.
      Simulated lesions were inserted into possum carcasses (n=48) at the peripheral
      lymph nodes. Carcasses were placed in the field at two sites (a tussock grassland
      and a podocarp-broadleaved forest site) and in two seasons (summer and winter)
      for up to 62 days. Survival rates of M. bovis were estimated by sampling the
      simulated lesions over time, and culturing the recovered lesion to determine if
      any viable M. bovis bacteria were present. The time taken for a free-ranging
      possum to first encounter a dead possum in its home range was estimated by live
      trapping possums and fitting them with proximity loggers (n=13). A 'contact' was
      recorded if these possums came within 40-50 cm of proximity loggers fitted to
      possum carcasses. RESULTS: There were strong seasonal and site effects in the
      survival rate of M. bovis in possum carcasses. In the grassland habitat, no
      viable bacilli were cultured from any carcass after 3 days in summer, whereas in
      winter all samples were culture-positive for the first 20 days, and some were
      still positive after 27 days. The survival rates for forest habitat were
      intermediate between the results for grassland, and there were no culture
      positive carcasses after 9 days in summer or 27 days in winter. In summer,
      infected carcasses (n=6) were first encountered by possums a mean 1.9 (range 0.4
      6.7) days after placement. CONCLUSIONS: Possum carcasses were contacted by free
      ranging possums within the period that viable M. bovis were shown to survive in a
      carcass. The risk of such infection is likely to be most significant in winter or
      in areas with microhabitats where the survival of M. bovis is high. However, the
      generally low survival rate of M. bovis in possum carcasses and the low frequency
      of possum-to-carcass contacts indicate this route of transmission alone could not
      maintain Tb in a possum population.

PMID- 21851298
TI  - Effect of vaccination and natural infection with Mycobacterium avium subsp.
      paratuberculosis on specificity of diagnostic tests for bovine tuberculosis in
      farmed red deer (Cervus elaphus).
AB  - AIM: To assess the effect of vaccination against paratuberculosis (Johne's
      disease) on reactivity to diagnostic tests for bovine tuberculosis (Tb) in deer
      exposed to natural challenge with Mycobacterium avium subsp. paratuberculosis
      (Map), and to investigate Map infection as a factor in Tb test cross-reactivity
      at the herd level. METHODS: In Study 1, yearling deer (n=180 vaccinates and n=181
      controls) were randomly selected from three commercial deer herds participating
      in a trial of a commercial vaccine against paratuberculosis. The deer were
      subjected to the comparative cervical skin test (CCT) for Tb at 44 weeks post
      vaccination. Interpretation as a mid-cervical tuberculin skin test (MCT) was also
      recorded. Serum from deer positive to the CCT was collected 3-4 weeks after
      tuberculin injection and tested using the ELISA Tb test (ETB), with both standard
      and the modified-ETB interpretations. In Study 2, 102 herds were categorised as
      infected or uninfected with Map based on results of pooled faecal culture, and
      positive to MCT if one or more deer gave a positive reaction to the MCT following
      testing in 2005. Information on other potential risk factors for MCT reactivity
      was collected using a standardised questionnaire conducted on each farm. The data
      were analysed using a multivariable logistic regression model. RESULTS: In Study
      1, 79/180 (44%) vaccinates and 42/181 (23%) controls were positive to the MCT
      (p<0.001). Two vaccinates (1.1%) that were CCT-positive were both positive to the
      standard ETB and negative to the modified ETB. One of three CCT-positive controls
      was negative to the standard ETB, and the other two were positive; both controls
      were modified ETB-positive. In Study 2, significantly more MCT-positive (41/58;
      71%) than MCT-negative (18/44; 41%) herds were infected with Map (p=0.003). The
      OR for a positive MCT for herds infected with Map was 3.1 (95% CI=1.3-7.5),
      compared with uninfected herds. Herd size was positively associated with a
      positive MCT result (p=0.004). CONCLUSIONS: Infection with Map and vaccination
      increased the risk of non-specificity of the MCT in deer herds. The CCT and
      ancillary testing of CCT-positive animals using the modified ETB are effective
      tools to address the reduced specificity of the MCT. However, where use of these
      tests is not permitted, non-specificity related to infection and vaccination will
      be more difficult to resolve.

PMID- 21851299
TI  - Dominant expression of interleukin-8 vs interleukin-1beta and tumour necrosis
      factor alpha in lungs of lambs experimentally infected with Mannheimia
      haemolytica.
AB  - AIMS: To quantify the number of cells infected with Mannheimia haemolytica and
      expressing interleukin (IL)-1beta, tumour necrosis factor alpha (TNFalpha) and IL
      8 using immunohistochemistry, and to measure the immunoreactivity of cytokines in
      pulmonary tissue extracts using ELISA, in the lung of lambs experimentally
      infected with M. haemolytica, and to compare the patterns of expression of
      cytokines in airways at different times post-infection (p.i.). METHODS: Twenty 3
      month-old lambs of both sexes were randomly assigned to two groups, viz infected
      (n=15), and uninfected controls (n=5). Each lamb in the infected group was
      inoculated with 1.5 x 10(9) cfu M. haemolytica in 5 mL sterile nutrient broth,
      control lambs were inoculated with 5 mL sterile nutrient broth and clinical signs
      were monitored. Infected and control animals were killed at 1, 3, 5, 7, and 15
      days p.i. Histopathology and immunohistochemistry were conducted to determine the
      number of immunolabelled cells in pneumonic lungs, and study the pattern of
      expression of IL-1beta, TNFalpha and IL-8 in lung extracts using ELISA. RESULTS:
      Lesions in bronchi and bronchioles ranged from epithelial desquamation to
      bronchiolitis obliterans and necrosis. The alveoli had areas of seroproteinaceous
      fluid, fibrin and bacterial aggregates that evolved to foci of pyogranulomatous
      inflammation with clustered inflammatory cells, referred to as 'oat cells'. M.
      haemolytica antigen was observed in the cytoplasm of inflammatory cells.
      Labelling of IL-1beta, TNFalpha and IL-8 was observed in bronchial and
      bronchiolar epithelial cells, alveolar exudate, and in interstitial inflammatory
      infiltrate, with increased expression on 1 and 3 days p.i. for IL-1beta and
      TNFalpha, and 1, 3, and 5 days p.i. for IL-8. In lung tissue extracts, peak
      concentrations of IL-1beta (55 (SD 5) ng/mL), TNFalpha (92 (SD 6) pg/mL) and IL-8
      (8 [SD 2] MUg/mL) occurred at 3 days p.i. CONCLUSIONS: The results of this study
      suggested that the inflammatory cytokines IL-1beta, TNFalpha and IL-8 may play an
      important role in enhancing the biological response to M. haemolytica, and
      contribute to the development of lesions in the lung in pulmonary pasteurellosis
      in sheep. Given that the expression of IL-8 in lung was much greater than that of
      IL-1beta and TNFalpha, anti-cytokine agents directed at this mediator could be
      useful in the prevention and treatment of this disease.

PMID- 21851300
TI  - Changes in concentrations of lysergol in urine and prolactin in plasma, rectal
      temperature and respiration rate in sheep selected for resistance or
      susceptibility to ryegrass staggers and fed ergovaline.
AB  - AIM: To determine the effects of feeding ryegrass seed containing ergovaline to
      sheep selected for resistance or susceptibility to ryegrass staggers on
      concentration of lysergol (a metabolite of ergovaline) in urine, prolactin in
      plasma, rectal temperature and respiration rate. METHODS: Two experiments were
      carried out using 12 Romney crossbred ewe lambs aged 9 months, comprising animals
      resistant (n=4), susceptible (n=4) or outcross (n=4) to ryegrass staggers. In
      Experiment 1, sheep were given either a single (Part A) or six (Part B) feed (s)
      of endophyte-infected seed containing ergovaline at 30 mg/kg dry matter (DM), at
      42 MUg ergovaline/kg bodyweight (BW), to simulate acute and chronic exposure to
      ergovaline, respectively. The concentration and excretion of lysergol in urine
      and concentration of prolactin in plasma were measured over 3 and 12 days, for
      Parts A and B respectively. In Experiment 2, after a recovery period of 7 days,
      the same sheep were fed with ergovaline at 67 MUg/kg of BW for 7 days. Soon after
      the seventh feed the sheep were moved to a hothouse at 36.5 degrees C and 60%
      humidity, and 3 h later their rectal temperatures and respiration rates were
      measured. RESULTS: The concentration of lysergol and excretion in urine increased
      to a peak between 6 and 9 h after exposure to ergovaline whereas the
      concentration of prolactin in plasma was markedly reduced. Differences in
      concentration and rate of excretion of lysergol in urine between animals
      resistant, outcross and susceptible to ryegrass staggers were not significant
      (p>0.1). The animals resistant to ryegrass staggers had a lower rectal
      temperature (p<0.05) and a faster respiration rate than the outcross and
      susceptible groups when exposed to high ambient temperature and high humidity.
      CONCLUSIONS: This study showed that excretion of lysergol in urine increased with
      each exposure of sheep to ergovaline. Animals genetically resistant to ryegrass
      staggers exhibited a lower rectal temperature and a faster respiration rate than
      those susceptible, demonstrating the possible cross resistance of sheep to
      ergovaline in a population originally selected for resistance to ryegrass
      staggers. Hence potential exists to select animals resistant to ryegrass staggers
      that are also resistant to ergovaline.

PMID- 21851301
TI  - Detection of Mycobacterium avium subsp. paratuberculosis in skeletal muscle and
      blood of ewes from a sheep farm in New Zealand.
AB  - AIM: To determine whether viable Mycobacterium avium subsp. paratuberculosis
      (Map) is present in skeletal muscle and blood in ewes with and without Johne's
      disease confirmed histologically. METHODS: A total of 51 mixed-aged ewes in poor
      body condition from a farm with a history of clinical Johne's disease were culled
      and examined at necropsy. BACTEC radiometric culture was performed on samples of
      skeletal muscle from the biceps femoris, mononuclear cells in peripheral blood
      (hereafter referred to as blood), and ileum. Histological sections and Ziehl
      Neelsen (ZN)-stained impression smears of terminal ileum and mesenteric lymph
      nodes were examined. Ewes were defined as having confirmed Johne's disease if
      there was histopathological evidence typical of the disease within the ileum and
      adjacent lymph nodes. RESULTS: Eighteen of 21 (86%) ewes with confirmed clinical
      Johne's disease were culture-positive for Map from sites peripheral to the
      alimentary tract, comprising 15 from skeletal muscle and 13 from blood. Five of
      30 (17%) ewes that did not have Johne's disease were culture-positive, with four
      from skeletal muscle and one from blood. The likelihood that ewes with confirmed
      Johne's disease had systemic Map infection compared with ewes without was
      determined as OR=30 (95% CI=6.3-142.0; p<0.001). CONCLUSION: The prevalence of
      Map infection of skeletal muscle and blood in ewes with confirmed Johne's disease
      was 71% and 62% respectively, and in unaffected ewes was 13% for muscle and 3%
      for blood. CLINICAL RELEVANCE: Skeletal muscle and blood are potential sources of
      exposure of humans to Map, and the risk appears higher from sheep with Johne's
      disease.

PMID- 21851302
TI  - Lipoleiomyoma of the reproductive tract in a Huntaway bitch.
AB  - CASE HISTORY: A marked perineal swelling was identified in a 4-year-old entire
      nulliparous Huntaway bitch. The mass was first observed at last oestrus, 6 months
      previously. CLINICAL FINDINGS: A diffuse swelling was visible in the perineum
      that extended from the anus to the vulva. The vulval commisure was distorted
      ventrolaterally. An extraluminal mass involved the vulva, vestibule and vagina.
      On rectal and vaginal examination the rostral extent could not be identified.
      There was no palpable intraluminal mass. The bitch produced a reduced urine flow,
      and there was complete voiding of the bladder. The urethra was not involved.
      Vaginal cytology suggested pro-oestrus. PATHOLOGICAL FINDINGS: Multiple fine
      needle aspirates were non-diagnostic. Incisional biopsies revealed extensive well
      differentiated fatty tissue with scattered bundles of collagen and occasional
      fascicles of smooth muscle. Following complete excisional biopsy the formalin
      fixed neoplasm weighed 714 g and measured 13 x 11 x 6 cm. Histologically, there
      was a thin outer layer of fibrous tissue, surrounding sheets of mature adipocytes
      and randomly distributed bundles of smooth muscle. Immunohistochemical findings
      were consistent with a smooth muscle neoplasm possessing oestrogen receptors.
      DIAGNOSIS: The clinical, gross, histological and immunohistochemical findings
      were consistent with a diagnosis of lipoleiomyoma expressing oestrogen receptors.
      CLINICAL RELAVANCE: A lipoleiomyoma should be considered a differential diagnosis
      for a benign tumour in the caudal reproductive tract of the bitch. Incisional and
      fine-needle aspiration biopsies of a lipoleiomyoma may resemble a lipoma.
      Excisional biopsy may be required for a definitive diagnosis. Lipoleiomyomas in
      the reproductive tract of the bitch may possess sex steroid receptors, and
      patients may benefit from ovariohysterectomy or hormonal therapies prior to
      excision.

PMID- 21851303
TI  - Fibrous osteodystrophy in two Northern Royal albatross chicks (Diomedea
      sanfordi).
AB  - CASE HISTORY: In February 2004, two Northern Royal albatross chicks aged 20 and
      25 days old were presented for necropsy. Both chicks had been hand-fed in situ at
      a breeding colony, from 2-3 days post-hatch. The hand-rearing diet consisted of
      boneless hoki fillets (Macraronus novaezelandiae), electrolytes, and sooty
      shearwater (Puffinus griseus) proventricular oil obtained as a by-product of
      cultural harvest. PATHOLOGICAL FINDINGS: Routine necropsies on the affected
      chicks revealed many bones were soft and easily bent. Radiography and
      histopathology revealed decreased bone density, pathological fractures, and
      extensive remodelling suggestive of fibrous osteodystrophy. DIAGNOSIS:
      Nutritional secondary hyperparathyroidism, resulting from an imbalance in the
      dietary Ca:P ratio. CLINICAL RELEVANCE: The imbalance in the dietary Ca:P ratio
      was a result of feeding deboned and eviscerated fish. This investigation also
      highlighted potential health risks associated with the practice of feeding stored
      rancid proventricular oil, including the destruction of fat-soluble vitamins. It
      is therefore possible that oxidative degradation of vitamin D may have
      contributed to the development of nutritional secondary hyperparathyroidism.
      Subsequently, dietary recommendations for supplementary feeding of orphaned
      Northern Royal albatross chicks include the feeding of whole human-grade fish
      with an appropriate Ca:P ratio, and the exclusion of proventricular oil. These
      cases highlight the need for scientific input into wildlife conservation
      projects, as lack of appropriate nutritional advice resulted in the feeding of a
      nutritionally inadequate diet. Following the recommended changes in diet, no
      further cases of osteodystrophy have been diagnosed in hand-raised chicks in the
      albatross colony.

PMID- 21851304
TI  - Probable avulsion of the infraspinatus tendon of insertion in a Rottweiler.
AB  - CASE HISTORY: An 8.5-month-old male Rottweiler was presented with chronic, non
      localisable, right forelimb lameness. CLINICAL FINDINGS: Survey radiographs
      revealed panosteitis in the right antebrachium and an irregularly marginated
      radiolucency on the lateral aspect of the proximal left humerus. The tendon of
      insertion of the left infraspinatus muscle was enlarged, some tendon fibres ended
      prematurely in a cluster of mineralised particles, and there was a large bony
      defect at the point of insertion. DIAGNOSIS: Probable avulsion of the left
      infraspinatus tendon. CLINICAL RELEVANCE: This case was particularly unusual due
      to the marked prominence of the lesion without lameness of the left forelimb.
      Avulsion of the infraspinatus tendon is poorly described in the veterinary and
      medical literature.

PMID- 21851305
TI  - Dermatosparaxis in two white Dorper lambs.
AB  - CASE HISTORY AND CLINICAL FINDINGS: Two White Dorper lambs from the North Island
      of New Zealand, 2 and 4 weeks of age, were presented with large skin flaps
      hanging from the flanks, separation of skin from the subcutis over mobile joints,
      and de-gloving injuries of the limbs and tail. The lambs were subject to
      euthanasia on humane grounds. PATHOLOGICAL FINDINGS: Large skin tears with
      associated haemorrhage, periarticular S/C oedema and generalised skin fragility
      were observed in both lambs at post-mortem examination. Histology of the affected
      skin revealed diffuse hyalinisation of dermal collagen compared with control
      lambs, protein-filled peri-adnexal clefts and areas of deep dermal and S/C
      granulation tissue consistent with previous separation of skin from the subcutis.
      Analysis of hair follicles, collected from one of the lambs, using a commercially
      available genetic test in Australia was consistent with the lamb being homozygous
      for the mutation responsible for ovine dermatosparaxis. DIAGNOSIS: Likely
      dermatosparaxis. CLINICAL RELEVANCE: These findings strongly suggest that the
      mutation responsible for dermatosparaxis in White Dorper sheep is present in New
      Zealand. Dermatosparaxis should be considered when investigating skin fragility
      in lambs with White Dorper genetics. Confirmation of the disorder is possible
      through genetic analysis of hair follicles.

PMID- 21851306
TI  - Modification to histopathological lesion severity score in red deer (Cervus
      elaphus) affected by Johne's disease.

PMID- 21851307
TI  - Preschoolers' emotion knowledge: self-regulatory foundations, and predictions of
      early school success.
AB  - Preschoolers (N=322 in preschool, 100 in kindergarten) were assessed
      longitudinally to examine the self-regulatory roots of emotion knowledge
      (labelling and situation) and the contributions of emotion knowledge to early
      school adjustment (i.e., including social, motivational, and behavioural
      indices), as well as moderation by age, gender, and risk. Age, gender, and risk
      differences in emotion knowledge were also examined. Emotion knowledge skills
      were found to be more advanced in older children and those not at economic risk,
      and in those with higher levels of self-regulation. Overall, the results support
      the role of emotion knowledge in early school adjustment and academic success
      even with gender, age, and risk covaried, especially for boys, older
      preschoolers, and those at economic risk.

PMID- 21851308
TI  - Advanced preformulation investigations for the development of a lead intravaginal
      bioadhesive polymeric device.
AB  - CONTEXT AND OBJECTIVE: To screen various polymers through extensive
      preformulation investigations to ultimately obtain a lead polymer combination for
      designing a desirable Intravaginal Bioadhesive Polymeric Device (IBPD). MATERIALS
      AND METHODS: Hydrophilic and hydrophobic polymers (18) at different combinations
      were blended and compressed into 62 caplet-shaped devices at 5 tons, one of the
      hydrophilic polymers being a modified synthetic product of polyamide 6,10 ((m)PA
      6,10). Two sets of crosslinked PAA-based caplets comprising either allyl-sucrose
      (AS-PAA) or allyl-penta-erythritol (APE-PAA) were explored. The devices were
      subjected to in-process validation tests and thereafter to preformulation
      investigational screening {equilibrium swelling ratio (ESR) being a screening
      parameter}, using a One Variable at a Time (OVAT) approach. Molecular mechanics
      force field simulations in both vacuum and solvated systems were conducted to
      investigate the influence of addition and subsequent replacement of a polymer(s)
      on the spatial disposition and energetic profile of the sterically constrained
      and geometrically optimized multi-polymeric complex, IBPD. RESULTS AND
      DISCUSSION: The developed devices were sufficiently strong (longitudinal crushing
      force:286 +/- 0.01 N; mean weight:600 +/- 0.48 mg; mean friability:0.31 +/-
      0.04%). Through OVAT approach, 15 lead formulations with minimal swelling
      tendencies (ESRs ranging from 0.011 to 0.084) were obtained out of 62
      formulations. F62 {i.e. (m)PA 6,10, (150 mg), PLGA (400 mg), EC (200 mg), PVA (25
      mg) and PAA (25 mg)} displayed minimal swelling tendency and therefore the
      highest stability. The highly stabilized conformation of the final in silico IBPD
      polymeric assembly PLGA-(m)PA6,10-PVA-PAA-EC corroborated the experimental
      results in terms of preformulation investigational screening using the OVAT
      approach. CONCLUSION: The results obtained suggest that (m)PA 6,10, PLGA, EC, PVA
      and PAA at an appropriate weight ratio may be suitable for development of an
      IBPD.

PMID- 21851309
TI  - Objective assessment of stress levels and health status using routinely measured
      clinical laboratory parameters as biomarkers.
AB  - Observed stress intensity was estimated using a scoring system from 0-100. Health
      status was estimated using the readily available laboratory measurements of C
      reactive protein, neutrophil count, and fasting plasma glucose. We found that the
      stress score determined was linked to patient health status. Further studies are
      indicated.

PMID- 21851310
TI  - Selection of oral bioavailability enhancing formulations during drug discovery.
AB  - The objective of this paper was to identify oral bioavailability enhancing
      approaches for a poorly water-soluble research compound during drug discovery
      stages using minimal amounts of material.   LCQ789 is a pBCS (preclinical BCS)
      Class II compound with extremely low aqueous solubility (<1 ug/mL) and high
      permeability, therefore, resulting in very low oral bioavailability in
      preclinical species (rats and dogs). A number of solubility and/or dissolution
      enhancing approaches including particle size reduction, solid dispersions, lipid
      based formulations and co-crystals, were considered in order to improve the
      compound's oral bioavailability. High-Throughput Screening (HTS) and in silico
      modeling (GastroPlusTM) were utilized to minimize the compound consumption in
      early discovery stages. In vivo evaluation of selected physical form and
      formulation strategies was performed in rats and dogs. Amongst the formulation
      strategies, optimized solid dispersion and lipid-based formulation provided
      significant improvement in drug dissolution rate and hence, oral bioavailability.
      In addition, a significant impact of physical form on oral bioavailability of
      LCQ789 was observed. In conclusion, a thorough understanding of not only the
      formulation technique but also the physical form of research compounds is
      critical to ensure physical stability, successful pharmacokinetic (PK) profiling
      and early developability risk assessment.

PMID- 21851311
TI  - Studying gender and injuries: a comparative analysis of the literatures on
      women's injuries in sport and work.
AB  - This article provides a review and analysis of the literatures on the gendering
      of injuries in sport and in work. It argues that, while research on women's work
      related injuries has considered the interaction of biological and social bases of
      risk, research on women's injuries in sport has concentrated to a greater extent
      on biological risk factors alone. The difference in emphasis between these two
      literatures has, in turn, provoked contrasting responses to these sets of
      research. While bringing women into the discussion of work-related injuries is
      seen as an advance, the profiling of women's sport-related injuries has been
      viewed with alarm by critics, who see this as a return to historical notions of
      women's frailty. The analysis suggests that contrasts between these bodies of
      research derive from differences in the social organisation of sport and work and
      the broader literatures on health and safety in each setting. The article
      highlights the importance of conceptualisations of gender in research agenda
      devoted to understanding health-related concerns. PRACTITIONER SUMMARY: The
      analysis presented here has important relevance to ergonomics because of the need
      to better understand how gender is implicated in ergonomics research and
      practice.

PMID- 21851312
TI  - Application of liposome encapsulation technique to improve anti-carcinoma effect
      of resveratrol.
AB  - AIM: The promising anti-tumor effect of resveratrol (RES) has aroused much
      interest in recent years, but its clinical application was seriously hindered due
      to its poor solubility in water. The aim of this study was to improve the water
      solubility of RES by liposome encapsulation technique for effective tumor
      treatment. METHODS: This study develops two liposomal formulations to solubilize
      RES by reverse-phase evaporation method with or without poly(ethylene glycol
      2000)-grafted distearolyl phosphatidylethanolamine (DSPE-PEG(2000)). The effect
      of different formulation factors on the encapsulation efficiency (EE) and the
      particle sizes were investigated. These factors included the mass ratio of drug
      to soybean phosphatidylcholine (drug/SPC), the mass ratio of cholesterol to
      soybean phosphatidylcholine (chol/SPC), the volume ratio of water phase/organic
      phase and the microfluidization process. The drug release studies were performed
      in various media, simulating the desired application conditions. The cytotoxicity
      study was carried out by MTT assay on HeLa and Hep G2 cell lines. RESULTS: The
      RES EE of 95% was obtained when using drug/SPC (1:40 mass ratio), Chol/SPC (1:10
      mass ratio), water phase/oil phase (1:2 volume ratio), microfluidization process
      (entrance pressure 6 kpa, two times of cycle time). The addition of DSPE
      PEG(2000) into the formulation showed little effect on the formation and
      properties of RES liposome. The release of RES was pH-independent. RES liposomes
      and PEG-modified liposomes performed significant inhibition effects on both cells
      growth due to the solubilized RES. CONCLUSION: RES can be effectively loaded into
      liposomes and its anti-cancer effect was evidently improved by the application of
      liposome encapsulation technique.

PMID- 21851313
TI  - Gender-specific differences in biomarkers responses to acute coronary syndromes
      and revascularization procedures.
AB  - A growing body of gender-related research in coronary artery disease is beginning
      to gradually elucidate differences between women and men. In patients presenting
      with acute coronary syndromes (ACS), these sex differences include varying risk
      factor profiles, accuracy of diagnostic testing, clinical presentations,
      treatment practices and outcomes. There is also a differential expression of
      cardiac biomarkers by sex, which remains unexplained. This paper reviews all the
      available information on the effect of gender on cardiac biomarkers by search of
      MEDLINE using the terms gender differences, biomarkers, ACS and revascularization
      procedures. A better understanding of the sex disparities in biomarkers along
      with all other clinical information is essential to optimal management and
      patient care in the future.

PMID- 21851314
TI  - The value of serum ischemia-modified albumin for assessing liver function in
      patients with chronic liver disease.
AB  - BACKGROUND: Ischemia-modified albumin (IMA), measured by the cobalt-binding
      capacity of albumin, is a promising biomarker for cardiac ischemia. The IMA-to
      serum albumin ratio (IMAR) has been reported to relate to the severity of
      decompensated liver cirrhosis. This study aimed to assess IMA and IMAR as a liver
      function test and to investigate whether albumin infusion changes IMAR in
      patients with liver cirrhosis. METHODS: Blood samples were collected from healthy
      volunteers (n=51) and patients with chronic hepatitis (n=25), liver cirrhosis
      (n=24) and uremia (n=13). Parameters examined included serum levels of IMA,
      albumin, total bilirubin, creatinine, international normalized ratio (INR), model
      for end-stage liver disease (MELD) score, child-turcotte-pugh (CTP) score,
      indocyanine green (ICG) retention rate and total antioxidant capacity (TAC).
      Paired serum samples from patients pre- and post-albumin infusion (n=9) were
      collected and the changes were compared. RESULTS: IMA and IMAR increased in
      patients with chronic hepatitis or cirrhosis, as compared to healthy volunteers.
      In patients with liver disease, IMA and IMAR were significantly associated with
      ICG retention, bilirubin, TAC and INR. In addition, IMAR was associated with CTP
      and MELD score in patients with cirrhosis. Albumin therapy improved patients'
      serum levels of creatinine and bilirubin and MELD score, but not IMA and IMAR.
      CONCLUSIONS: IMAR, reflecting liver function and oxidative stress, is a more
      objective liver function test as it was not affected after a 3-day albumin
      infusion. More investigations, however, are needed to validate the use of IMAR in
      cases of chronic liver disease.

PMID- 21851315
TI  - Effect of external marker sets on between-day reproducibility of knee kinematics
      and kinetics in stair climbing and level walking.
AB  - The purpose of this study was to compare the between-day repeatability of the
      knee kinematics and kinetics in stair climbing and level walking among three
      marker sets: the Helen-Hays marker set with some markers on well-defined bony
      landmarks and some on not well-defined locations on soft tissues, the modified
      Helen-Hays marker set with a static calibration trial, and the UNC-CH marker set
      with all marker on well defined bony landmarks and a static calibration trial.
      Three-dimensional coordinates of markers in stair climbing and level walking were
      collected for six subjects on three days. Three-dimensional knee joint angles and
      resultant forces and moments were calculated. A between-day coefficient of
      multiple correlation was used to represent between-day repeatability of the knee
      joint angles, and resultant forces and moments during the stance phases of the
      stair climbing and level walking. Marker set had significant effect on the knee
      joint angles and resultant forces and moments (p < 0.02), except the knee axial
      force. The modified Helen-Hays marker set with a static calibration significantly
      improved the between-day repeatability for most of the knee angles and resultant
      forces and moments. The UNC-CH marker set with all markers on well-defined bony
      landmarks and a static calibration trial further improved the between-day
      repeatability of most the knee angles and resultant forces and moments.

PMID- 21851316
TI  - Angular movements of the trunk and pelvis when stepping over obstacles of
      different heights.
AB  - This study was performed to investigate the effect of obstacle height on the
      angular movements of the trunk and pelvis. Seven healthy subjects (all men)
      participated in the study (age: 22.0 +/- 1.2 years; height: 1.73 +/- 0.05 m;
      mass: 69.1 +/- 7.9 kg). Subjects were instructed to perform unobstructed level
      walking and to step over obstacles corresponding to 5%, 10%, and 15% of each
      subject's height. The video-based WINanalyze 3D motion measurement system was
      used to measure the three-dimensional (3D) angular movements of the trunk and
      pelvis. In the frontal and horizontal planes, peak-to-peak amplitudes of trunk
      rotation developed as the obstacle height increased. However, peak-to-peak
      amplitudes of pelvic rotation were not significantly different when stepping over
      obstacles of different heights. The coefficients, which revealed the degree of
      synchrony of the shoulder and pelvis, showed a trend of decreasing as the
      obstacle height increased. These results suggest that stepping over obstacles
      poses a significant challenge to the coordination of the trunk and pelvis. Pelvic
      rotation is important in adjusting the crossing stride and clearing an obstacle.
      In coordination with the pelvic motion, the shoulder plays a role in maintaining
      dynamic equilibrium when stepping over obstacles.

PMID- 21851317
TI  - Infection and the elite athlete: a review.
AB  - Light to moderate exercise has been associated with an increase in immune
      function and reduced risk of infectious diseases. Conversely, heavy exercise has
      been implicated in suppression of many immune parameters and a concomitant
      increased risk of infectious diseases. Infections can result in lost training
      time and negatively affect the performance of the elite athlete. Exercising
      during an infection can also increase the risk of secondary complications, such
      as viral myocarditis and post-viral fatigue syndrome. In addition to
      immunosuppression, other factors responsible for increased infection rates among
      athletes are close bodily contact with other people during training and
      competition, and environmental factors during the pursuit of sporting activities
      that increase exposure to pathogens. Although there is a generally higher risk of
      infection among athletes compared to the general population, some sports are
      associated with a particularly high risk for certain infections. These are skin
      infections in rugby and wrestling, infections of the foot in long-distance
      runners, and ear infections in those involved in water sports. Upper respiratory
      tract infections are the most frequently reported disability among all athletes
      and are the cause of more lost training days than all other infections put
      together. Transmission of blood-borne pathogens, although very uncommon in the
      athletic setting, are the cause of the most serious infections an athlete may
      develop. When considering the negative impact of infections on performance, it
      seems prudent that athletes use interventions to decrease the immunosuppressive
      effects of heavy exercise, and to minimize exposure to pathogens as far as
      practically possible. Management of the infected athlete is especially important
      if there is to be a speedy return to full training, and if the incidence of a
      relapse or secondary complications are to be minimized.

PMID- 21851318
TI  - Cycling with video feedback improves performance in untrained, but not in trained
      women.
AB  - The objectives of this study were to assess whether exercise performance
      responses could be altered when subjects were exposed to interactive video
      feedback and music (VFM), compared to music only feedback (M). Ten women, 5 well
      trained (46.4 +/- 4.7 ml * kg(-1) * min(-1)) and 5 untrained (34.5 +/- 5.7 ml *
      kg(-1) * min(-1)) participated in the study. Neither the trained nor the
      untrained group exhibited significant differences in HR and VO2 between the VFM
      and M conditions. The trained subjects cycled at similar speeds and for similar
      distances during the VFM and M conditions, and also cycled at a higher average
      speed (23.5 +/- 2.1 vs. 15.6 +/- 3.2 km * h(-1)) and further (11.9 +/- 1.1 vs.
      7.8 +/- 1.6 km) than the untrained subjects (p < 0.01). The untrained subjects
      cycled further and faster in the VFM versus M condition (p < 0.05), and both the
      average speed (15.6 +/- 3.2 vs. 13.9 +/- 2.3 km * h(-1)) and average distance
      cycled (7.8 +/- 1.6 vs. 7.0 +/- 1.2 km) were also improved in the VFM versus M
      condition (p < 0.05). No group or exercise condition differences were observed
      for ratings of perceived exertion or psychological performance. We conclude that
      VFM does not improve cycling performance in trained women, but untrained women
      cycle faster and further during a 30-min exercise session when exposed to a
      combination of interactive video and music feedback.

PMID- 21851319
TI  - Gait and metabolic adaptation of walking with negative heel shoes.
AB  - The purpose of this study was to explore the gait pattern and metabolic responses
      of walking with negative heel shoes as compared to walking with normal shoes.
      Nineteen female subjects were recruited, of whom 13 (aged 23.08 +/- 3.9 years,
      body weight 50.18 +/- 5.3 kg, and body height 1.63 +/- 0.05 m) participated in
      the gait pattern study, and 6 (age 32.8 +/- 6.6 years, body weight 58.3 +/- 5.8
      kg, and body height 1.64 +/- 0.01 m) in the metabolic study. In the gait pattern
      study, movement kinematics and kinetic data were obtained by video analysis and
      force platform measurement during the process of walking at a constant speed of
      1.33 m/s on a treadmill and over ground, respectively. In the metabolic study,
      heart rate and oxygen consumption were monitored during treadmill walking. The
      results showed that there was a significant difference between walking on a
      treadmill with negative heel shoes and walking with normal shoes, in terms of
      stride cycle time, cadence, stride length, and angles of the ankle, knee, and hip
      joints. Differences also were found with the maximum and minimum ground reaction
      forces and their occurrence times. Metabolically, heart rate and oxygen
      consumption showed a significant difference. In conclusion, walking with negative
      heel shoes induced significant changes in gait patterns, ground reaction forces,
      and energy consumption.

PMID- 21851320
TI  - Enzyme research and applications in biotechnological intensification of biogas
      production.
AB  - Biogas technology provides an alternative source of energy to fossil fuels in
      many parts of the world. Using local resources such as agricultural crop remains,
      municipal solid wastes, market wastes and animal waste, energy (biogas), and
      manure are derived by anaerobic digestion. The hydrolysis process, where the
      complex insoluble organic materials are hydrolysed by extracellular enzymes, is a
      rate-limiting step for anaerobic digestion of high-solid organic solid wastes.
      Biomass pretreatment and hydrolysis are areas in need of drastic improvement for
      economic production of biogas from complex organic matter such as lignocellulosic
      material and sewage sludge. Despite development of pretreatment techniques, sugar
      release from complex biomass still remains an expensive and slow step, perhaps
      the most critical in the overall process. This paper gives an updated review of
      the biotechnological advances to improve biogas production by microbial enzymatic
      hydrolysis of different complex organic matter for converting them into
      fermentable structures. A number of authors have reported significant improvement
      in biogas production when crude and commercial enzymes are used in the
      pretreatment of complex organic matter. There have been studies on the
      improvement of biogas production from lignocellulolytic materials, one of the
      largest and renewable sources of energy on earth, after pretreatment with
      cellulases and cellulase-producing microorganisms. Lipids (characterised as oil,
      grease, fat, and free long chain fatty acids, LCFA) are a major organic compound
      in wastewater generated from the food processing industries and have been
      considered very difficult to convert into biogas. Improved methane yield has been
      reported in the literature when these lipid-rich wastewaters are pretreated with
      lipases and lipase-producing microorganisms. The enzymatic treatment of mixed
      sludge by added enzymes prior to anaerobic digestion has been shown to result in
      improved degradation of the sludge and an increase in methane production.
      Strategies for enzyme dosing to enhance anaerobic digestion of the different
      complex organic rich materials have been investigated. This review also
      highlights the various challenges and opportunities that exist to improve
      enzymatic hydrolysis of complex organic matter for biogas production. The
      arguments in favor of enzymes to pretreat complex biomass are compelling. The
      high cost of commercial enzyme production, however, still limits application of
      enzymatic hydrolysis in full-scale biogas production plants, although production
      of low-cost enzymes and genetic engineering are addressing this issue.

PMID- 21851321
TI  - Dual activity of pyocyanin from Pseudomonas aeruginosa--antibiotic against
      phytopathogen and signal molecule for biofilm development by rhizobia.
AB  - The purified pyocyanin from Pseudomonas aeruginosa TO3 was investigated for its
      antagonistic activity against Macrophomina phaseolina and as a signaling molecule
      for development of biofilm by rhizobial strain Ca2. The antagonistic activity of
      purified pyocyanin, as determined by a dry mass method, showed inhibition of M.
      phaseolina. Biofilm formation by strain Ca2 was performed by crystal violet
      assay. There was an increase in biofilm development by Ca2 with an increase in
      pyocyanin concentration up to 0.12 nmol.L(-1), followed by a reduction. Using a
      well-diffusion method, we determined the effect of pyocyanin on disease
      suppression and biofilm formation by strain Ca2 on radicles of groundnut (
      Arachis hypogaea L. ) placed in three concentric whorls on water agar plates.
      Pyocyanin suppressed disease better at high concentration; however, at lower
      concentrations increased colony-forming units of Ca2 on radicles of seedlings was
      observed. A field study in soil infested with M. phaseolina showed that a
      coinoculant of P. aeruginosa TO3 and rhizobial strain Ca2 enhanced nodule mass
      and nitrogenase activity by 264.38% and 269.06%, respectively, over that of the
      control. This study reports that application of pyocyanin-producing pseudomonads
      together with rhizobia contributes to the enhancement of nodulation ability and
      better sustains the growth and productivity of groundnut even in the presence of
      M. phaseolina.

PMID- 21851322
TI  - Effects of midazolam and phenobarbital on brain oxidative reactions induced by
      pentylenetetrazole in a convulsion model.
AB  - CONTEXT: Brain oxidative reactions are involved in epilepsy as well as
      neurodegenerative diseases. In animal convulsion models, some anticonvulsants
      have been found to suppress oxidative reactions associated with convulsions.
      However, the effect of anticonvulsants on brain oxidative reactions has not fully
      been clarified. OBJECTIVE: Midazolam and phenobarbital are often used as an
      intravenous anesthetic, and are known to have anticonvulsive effect, but
      antioxidative effect of these drugs has rarely been studied. Thus, the purpose of
      this study was to evaluate the effects of these drugs on the degree of
      convulsions and brain oxidative reactions in an animal convulsion model.
      MATERIALS AND METHODS: In order to evaluate brain oxidative reactions, we
      measured malondialdehyde (MDA) level and heme oxygenase (HO)-1 mRNA expression
      level in the brain of mice in a convulsion model generated by a single injection
      of pentylenetetrazole (PTZ). We evaluated the effects of midazolam and
      phenobarbital on the degree of PTZ-induced convulsions and on the changes in
      brain MDA level and HO-1 mRNA expression level. RESULTS: After PTZ injection,
      severe convulsions were observed in all mice. MDA level was increased in the
      whole brain, while HO-1 mRNA expression level was increased only in the
      hippocampus. Both midazolam and phenobarbital prevented the convulsions and
      suppressed the increase in both MDA level and HO-1 mRNA expression level in the
      brain. CONCLUSION: In this study, both midazolam and phenobarbital suppressed PTZ
      induced MDA and HO-1 reactions in the brain, suggesting that these drugs inhibit
      brain oxidative reactions in a convulsion model.

PMID- 21851323
TI  - Noninvasive evaluation of contractile behavior of cardiomyocyte monolayers based
      on motion vector analysis.
AB  - A noninvasive method for the characterization of cardiomyocyte contractile
      behavior is presented. Light microscopic video images of cardiomyocytes were
      captured with a high-speed camera, and motion vectors (which have a velocity
      dimension) were calculated with a high spatiotemporal resolution using a block
      matching algorithm. This method could extract contraction and relaxation motions
      of cardiomyocytes separately and evaluate characteristics such as the beating
      rate, orientation of contraction, beating cooperativity/homogeneity in the
      monolayer, and wave propagation of impulses. Simultaneous phase-contrast imaging
      and calcium (Ca2+) fluorescence measurements confirmed that the timing of the
      maximum shortening velocity of cardiomyocytes correlated well with intracellular
      Ca2+ transients. Based on our analysis, gap junction inhibitors, 1-heptanol (2
      mM) or 18-beta-glycyrrhetinic acid (30 MUM), resulted in clear changes in beating
      cooperativity and the propagation pattern of impulses in the cardiomyocyte
      monolayer. Additionally, the time dependence of the motion vector length
      indicated a prolonged relaxation process in the presence of potassium (K+)
      channel blockers, dl-sotalol (1 MUM), E-4031 (100 nM), or terfenadine (100 nM),
      reflecting the prolonged QT (Q wave and T wave) interval of cardiomyocytes.
      Effects of autonomic agents (acetylcholine or epinephrine [EPI]) or EPI and
      propranolol on cardiomyocytes were clearly detected by the alterations of beating
      rate and the motion vector length in contraction and relaxation processes. This
      method was noninvasive and could sensitively evaluate the contractile behavior of
      cardiomyocytes; therefore, it may be used to study and/or monitor cardiomyocyte
      tissue during prolonged culture periods and in screens for drugs that may alter
      the contraction of cardiomyocytes.

PMID- 21851326
TI  - Vaccinia and other viruses with available vaccines show marked homology with the
      HIV-1 envelope glycoprotein: the prospect of using existing vaccines to stem the
      AIDS pandemic.
AB  - Cross-reactive immunity occurs when infection with or vaccination against one
      virus protects against another related family member. A search for homologues of
      the HIV-1 envelope glycoprotein revealed that it is composed of thousands of
      intercalating and overlapping viral matches of pentapeptide or longer gapped
      consensi, belonging to over 70% of the currently sequenced virome, infecting all
      kingdoms from bacteria to man. It was also highly homologous to proteins from the
      Visna/Maedi and other ovine viruses, while other proteins (nef/tat/gag/pol) were
      homologous to proteins from the equine infectious anaemia virus and HTLV-2/HTLV-3
      viruses. This phenomenon suggests that horizontal gene transfer from coinfecting
      RNA and DNA viruses to retroviruses is extensive, providing a route for the
      subsequent insertion of non-retroviral genes into human and other genomes via
      retroviral integration. This homology includes all viruses for which vaccines
      already exist. Cross-reactive immunity may be operative in AIDS, as Vaccinia
      vaccination decreases viral replication in HIV-1 infected patients' cells, for
      the CCR5 tropic form. Measles, Dengue virus, or GB virus C infections also
      decrease the HIV-1 viral load. A resumption of Vaccinia/smallpox vaccination
      might be expected to have a significant effect on the AIDS pandemic, and a
      careful study of the potential uses of other existing viral and bacterial
      vaccines merits close attention. This phenomenon may also be relevant to other
      recalcitrant viruses, bacteria, and parasites for which no vaccine exists and the
      armory of existing vaccines may have a role to play in diseases other than those
      for which they were designed.

PMID- 21851327
TI  - Exploring the determinants of the graded structure of vocal emotion expressions.
AB  - We examined what determines the typicality, or graded structure, of vocal emotion
      expressions. Separate groups of judges rated acted and spontaneous expressions of
      anger, fear, and joy with regard to their typicality and three main determinants
      of the graded structure of categories: category members' similarity to the
      central tendency of their category (CT); category members' frequency of
      instantiation, i.e., how often they are encountered as category members (FI); and
      category members' similarity to ideals associated with the goals served by its
      category, i.e., suitability to express particular emotions. Partial correlations
      and multiple regression analysis revealed that similarity to ideals, rather than
      CT or FI, explained most variance in judged typicality. Results thus suggest that
      vocal emotion expressions constitute ideal-based goal-derived categories, rather
      than taxonomic categories based on CT and FI. This could explain how prototypical
      expressions can be acoustically distinct and highly recognisable but occur
      relatively rarely in everyday speech.

PMID- 21851324
TI  - Transmitted drug resistance among antiretroviral-naive patients with established
      HIV type 1 infection in Santo Domingo, Dominican Republic and review of the Latin
      American and Caribbean literature.
AB  - Emergence of HIV resistance is a concerning consequence of global scale-up of
      antiretroviral therapy (ART). To date, there is no published information about
      HIV resistance from the Dominican Republic. The study's aim was to determine the
      prevalence of transmitted drug resistance (TDR) to reverse transcriptase and
      protease inhibitors in a sample of chronically HIV-1-infected patients in one
      clinic in Santo Domingo. The data are presented in the context of a review of the
      TDR literature from Latin America and the Caribbean. Genotype testing was
      successfully performed on 103 treatment-naive adults planning to initiate
      antiretroviral therapy; the World Health Organization (WHO) list of surveillance
      drug resistance mutations (SDRM) was used to determine the presence of TDR
      mutations. WHO SDRM were identified in eight patients (7.8%); none had received
      sdNVP. There were no significant differences in epidemiologic or clinical
      variables between those with or without WHO SDRM. The prevalence of WHO SDRM was
      1.0% and 6.8% for nucleoside reverse transcriptase inhibitors and nonnucleoside
      reverse transcriptase inhibitors, respectively. No WHO SDRMs for protease
      inhibitors were identified. Among 12 studies of TDR in the region with a sample
      size of at least 100 subjects, the reported prevalence of SDRM ranged from 2.8%
      to 8.1%. The most commonly identified SDRM was K103N. This information adds to
      our understanding of the epidemiology of TDR in the region and the possible role
      such mutations could play in undermining first-line treatment. Ongoing
      surveillance is clearly needed to better understand the TDR phenomenon in the
      Caribbean.

PMID- 21851328
TI  - Hydrolysis of flavonoid glycosides by propolis beta-glycosidase.
AB  - Flavonoids generally occur as O-glycosides with sugars bound in nature, while
      aglycones and their derivatives are the main flavonoids in propolis. The
      objective of this work was to study the propolis beta-glycosidase activities
      toward flavonoid beta-glycosides and their conjugated forms. beta-Glycosidase was
      extracted from propolis, incubated with flavonoid glycosides, and analysed for
      aglycone formation by HPLC. The results demonstrated that glucose conjugates were
      rapidly hydrolysed, but not conjugates with other sugars, i.e. rutin and
      naringin. The rate and extent of deglycosylation depends on the structure of the
      flavonoid and the position of the sugar substituitions. Quercetin 3-O-glucoside
      had the highest percent of hydrolysis, while quercetin 7-O-glucoside was the
      least hydrolysed. The K(m) values for hydrolysis of apigenin 7-glucoside and
      luteolin-7-O-glucoside were 13 uM and 20 uM, respectively.

PMID- 21851329
TI  - Explorations of clinical trials and pharmacovigilance databases of MF59(r)
      adjuvanted influenza vaccines for associated cases of narcolepsy: a six-month
      update.

PMID- 21851331
TI  - Pathogenesis of Lady Windermere syndrome.

PMID- 21851330
TI  - Tipranavir in highly antiretroviral treatment-experienced patients: Results from
      a French prospective cohort.
AB  - BACKGROUND: In highly antiretroviral-experienced patients with a multidrug
      resistant human immunodeficiency virus (HIV) infection, recommended regimens
      should preferentially contain 3 active components, including a ritonavir-boosted
      protease inhibitor (PI/r). Tipranavir/r (TPV/r), a non-peptidic PI, has been
      specifically developed for patients resistant to the usual antiretroviral classes
      including PIs. This paper discusses the role of TPV/r in patients experiencing
      multiple PI resistance. METHODS: Virological, immunological, and safety outcomes
      were collected between 2003 and 2007 at 7 clinical units. Virus resistance
      assessment was based on 3 different genotypic tests. The 207 patients evaluated
      had previously received nucleoside reverse transcriptase inhibitors (NRTIs) and
      PIs. RESULTS: The main drugs co-administered with TPV/r were 1 or 2 NRTIs
      associated, in half of the patients, with enfuvirtide. After 12 weeks, viral load
      was <50 copies/ml in 38% of the patients (44% with enfuvirtide), while median CD4
      counts had increased from 150 to 250 cells/mm3. Genotypic testing suggested that
      most of the patients had viruses susceptible to TPV. Lipid and transaminase
      levels were slightly modified, and less than 10% of treatment discontinuations
      were due to gastrointestinal events. CONCLUSION: A regimen including TPV/r
      associated with at least 1 active component is a valuable option in highly ARV
      experienced patients with multi-resistance to the usual ARV classes including
      PIs.

PMID- 21851332
TI  - Pharmacokinetics and protein binding of linezolid in cerebrospinal fluid and
      serum in a case of post-neurosurgical bacterial meningitis.
AB  - We describe a case of bacterial meningitis in a patient administered linezolid
      (LZD). The ratio of free to total LZD concentrations in cerebrospinal fluid (CSF)
      was 1 for all measurements, and the LZD concentration in CSF measured at the
      trough level was almost the same as the free serum concentration.

PMID- 21851333
TI  - Microbiological and molecular characterization of human clinical isolates of
      Staphylococcus cohnii, Staphylococcus hominis, and Staphylococcus sciuri.
AB  - BACKGROUND: The incidence of coagulase-negative staphylococci reported as
      causative agents of nosocomial infections has risen in the last decade. The aim
      of this study was to characterize biofilm formation, antibiotic resistance,
      SCCmec type, and genetic relatedness in clinical isolates of Staphylococcus
      cohnii, Staphylococcus hominis, and Staphylococcus sciuri recovered from humans.
      METHODS: Clinically relevant isolates of S. cohnii (n = 15), S. hominis (n = 9),
      and S. sciuri (n = 6), were collected from patients. Biofilm formation was
      evaluated using crystal violet staining, drug susceptibility was assessed using
      the broth microdilution method, and methicillin resistance was measured using the
      cefoxitin disk test. SCCmec was typed using 2 different methodologies, and
      genetic relatedness was determined by pulsed-field gel electrophoresis (PFGE).
      RESULTS: Sixty percent (9/15) of S. cohnii, 33% (3/9) of S. hominis, and 50%
      (3/6) of S. sciuri isolates were categorized as weak producers of biofilm. None
      of the isolates were resistant to vancomycin or linezolid. All 3 species showed a
      high resistance (> 66%) to ampicillin, levofloxacin, erythromycin, and
      ceftriaxone, and the majority of the isolates were methicillin-resistant. PFGE
      revealed that the S. cohnii isolates comprised 1 dominant clone. CONCLUSIONS: The
      S. cohnii, S. hominis, and S. sciuri isolates analyzed in this study showed a
      high methicillin resistance and resistance to other antimicrobials. The results
      of this study strongly suggest that coagulase-negative staphylococci harbour new
      SCCmec elements. We report the first case of a clone of S. cohnii associated with
      human disease.

PMID- 21851334
TI  - The natural YMDD mutations of hepatitis B virus in Western China.
AB  - BACKGROUND: To provide a scientific basis for clinical genetic diagnosis before
      lamivudine treatment in hepatitis B virus (HBV) patients, the rate of natural
      YMDD mutations in Western China and the correlations between YMDD mutations and
      several factors were investigated in this study. METHODS: A pyrosequencing
      approach for detecting YMDD mutations was first developed. The sensitivity of the
      pyrosequencing approach was determined by assaying polymerase chain reaction
      (PCR) products generated from 10-fold serial dilutions of HBV DNA and PCR
      products from mixed control plasmids with different ratios. Natural YMDD
      mutations in Western China were evaluated by analyzing the clinical samples from
      HBV patients who had no experience of using lamivudine, and the existence of YMDD
      mutants was further confirmed by real-time PCR. RESULTS: With the developed
      pyrosequencing approach, YMDD mutations could be determined within 2 h after PCR
      amplification. About 10 copies of HBV DNA per reaction were required to obtain
      sufficient PCR products to produce clear and accurate pyrosequencing patterns.
      The pyrosequencing approach developed had the capacity to detect minor mutants;
      most HBV mutants in samples were minor ones. The rate of natural YMDD mutations
      in Western China was 15.56%. The hepatitis B e antigen (HBeAg) level in serum was
      correlated with YMDD mutations. CONCLUSIONS: In Western China, natural YMDD
      mutations occur at a rate of 15.56%, and it is suggested that pyrosequencing be
      performed to detect YMDD mutations before lamivudine treatment in patients with a
      chronic HBV infection.

PMID- 21851335
TI  - Cross-pharmacology analysis of G protein-coupled receptors.
AB  - The degree of applicability of chemogenomic approaches to protein families
      depends on the accuracy and completeness of pharmacological data and the
      corresponding level of pharmacological similarity observed among their protein
      members. The recent public domain availability of pharmacological data for
      thousands of small molecules on 204 G protein-coupled receptors (GPCRs) provides
      a firm basis for an in-depth cross-pharmacology analysis of this superfamily. The
      number of protein targets included in the cross-pharmacology profile of the
      different GPCRs changes significantly upon varying the ligand similarity and
      binding affinity criteria. However, with the exception of muscarinic receptors,
      aminergic GPCRs distinguish themselves from the rest of the members in the family
      by their remarkably high levels of pharmacological similarity among them.
      Clusters of non-GPCR targets related by cross-pharmacology with particular GPCRs
      are identified and the implications for unwanted side-effects, as well as for
      repurposing opportunities, discussed.

PMID- 21851336
TI  - Receptor-isoform-selective insulin analogues give tissue-preferential effects.
AB  - The relative expression patterns of the two IR (insulin receptor) isoforms, +/-
      exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have
      developed insulin analogues with different binding affinities for the two
      isoforms to test whether tissue-preferential biological effects can be attained.
      In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat
      (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a
      consequence, the insulin analogue INS-A, which has a higher relative affinity for
      human IR-A, had a higher relative potency [compared with HI (human insulin)] for
      glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in
      rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the
      INS-B analogue, which has an increased affinity for human IR-B, had higher
      relative potencies (compared with HI) for inducing glycogen accumulation (75%)
      and lipogenesis (130%) than for affecting muscle (45%). For the same blood
      glucose-lowering effect upon acute intravenous dosing of mice, INS-B gave a
      significantly higher degree of IR phosphorylation in liver than HI. These in
      vitro and in vivo results indicate that insulin analogues with IR-isoform
      preferential binding affinity are able to elicit tissue-selective biological
      responses, depending on IR-A/IR-B expression.

PMID- 21851337
TI  - Salmonella enterica serotype Typhimurium usurps the scaffold protein IQGAP1 to
      manipulate Rac1 and MAPK signalling.
AB  - Salmonella enterica serotype Typhimurium invades eukaryotic cells by re-arranging
      the host-cell cytoskeleton. However, the precise mechanisms by which Salmonella
      induces cytoskeletal changes remain undefined. IQGAP1 (IQ motif-containing GTPase
      activating protein 1) is a scaffold protein that binds multiple proteins
      including actin, the Rho GTPases Rac1 and Cdc42 (cell division cycle 42), and
      components of the MAPK (mitogen-activated protein kinase) pathway. We have shown
      previously that optimal invasion of Salmonella into HeLa cells requires IQGAP1.
      In the present paper, we use IQGAP1-null MEFs (mouse embryonic fibroblasts) and
      selected well-characterized IQGAP1 mutant constructs to dissect the molecular
      determinants of Salmonella invasion. Knockout of IQGAP1 expression reduced
      Salmonella invasion into MEFs by 75%. Reconstituting IQGAP1-null MEFs with wild
      type IQGAP1 completely rescued invasion. By contrast, reconstituting IQGAP1-null
      cells with mutant IQGAP1 constructs that specifically lack binding to either
      Cdc42 and Rac1 (termed IQGAP1DeltaMK24), actin, MEK [MAPK/ERK (extracellular
      signal-regulated kinase) kinase] or ERK only partially restored Salmonella entry.
      Cell-permeant inhibitors of Rac1 activation or MAPK signalling reduced Salmonella
      invasion into control cells by 50%, but had no effect on bacterial entry into
      IQGAP1-null MEFs. Importantly, the ability of IQGAP1DeltaMK24 to promote
      Salmonella invasion into IQGAP1-null cells was abrogated by chemical inhibition
      of MAPK signalling. Collectively, these results imply that the scaffolding
      function of IQGAP1, which integrates Rac1 and MAPK signalling, is usurped by
      Salmonella to invade fibroblasts and suggest that IQGAP1 may be a potential
      therapeutic target for Salmonella pathogenesis.

PMID- 21851338
TI  - Retinaldehyde is a substrate for human aldo-keto reductases of the 1C subfamily.
AB  - Human AKR (aldo-keto reductase) 1C proteins (AKR1C1-AKR1C4) exhibit relevant
      activity with steroids, regulating hormone signalling at the pre-receptor level.
      In the present study, investigate the activity of the four human AKR1C enzymes
      with retinol and retinaldehyde. All of the enzymes except AKR1C2 showed
      retinaldehyde reductase activity with low Km values (~1 MUM). The kcat values
      were also low (0.18-0.6 min-1), except for AKR1C3 reduction of 9-cis
      retinaldehyde whose kcat was remarkably higher (13 min-1). Structural modelling
      of the AKR1C complexes with 9-cis-retinaldehyde indicated a distinct conformation
      of Trp227, caused by changes in residue 226 that may contribute to the activity
      differences observed. This was partially supported by the kinetics of the AKR1C3
      R226P mutant. Retinol/retinaldehyde conversion, combined with the use of the
      inhibitor flufenamic acid, indicated a relevant role for endogenous AKR1Cs in
      retinaldehyde reduction in MCF-7 breast cancer cells. Overexpression of AKR1C
      proteins depleted RA (retinoic acid) transactivation in HeLa cells treated with
      retinol. Thus AKR1Cs may decrease RA levels in vivo. Finally, by using
      lithocholic acid as an AKR1C3 inhibitor and UVI2024 as an RA receptor antagonist,
      we provide evidence that the pro-proliferative action of AKR1C3 in HL-60 cells
      involves the RA signalling pathway and that this is in part due to the
      retinaldehyde reductase activity of AKR1C3.

PMID- 21851339
TI  - 5'-AMP-activated protein kinase is inactivated by adrenergic signalling in adult
      cardiac myocytes.
AB  - In adult rat cardiac myocytes adrenaline decreased AMPK (AMP-activated protein
      kinase) activity with a half-time of approximately 4 min, decreased
      phosphorylation of AMPK (alpha-Thr172) and decreased phosphorylation of ACC
      (acetyl-CoA carboxylase). Inactivation of AMPK by adrenaline was through both
      alpha1- and beta-ARs (adrenergic receptors), but did not involve cAMP or calcium
      signalling, was not blocked by the PKC (protein kinase C) inhibitor BIM I
      (bisindoylmaleimide I), by the ERK (extracellular-signal-regulated kinase)
      cascade inhibitor U0126 or by PTX (pertussis toxin). Adrenaline caused no
      measurable change in LKB1 activity. Adrenaline decreased AMPK activity through a
      process that was distinct from AMPK inactivation in response to insulin or PMA.
      Neither adrenaline nor PMA altered the myocyte AMP:ATP ratio although the
      adrenaline effect was attenuated by oligomycin and by AICAR (5-amino-4
      imidazolecarboxamide-1-beta-D-ribofuranoside), agents that mimic 'metabolic
      stress'. Inactivation of AMPK by adrenaline was abolished by 1 MUM okadaic acid
      suggesting that activation of PP2A (phosphoprotein phosphatase 2A) might mediate
      the adrenaline effect. However, no change in PP2A activity was detected in
      myocyte extracts. Adrenaline increased phosphorylation of the AMPK beta-subunit
      in vitro but there was no detectable change in vivo in phosphorylation of
      previously identified AMPK sites (beta-Ser24, beta-Ser108 or beta-Ser182)
      suggesting that another site(s) is targeted.

PMID- 21851340
TI  - Length of the active-site crossover loop defines the substrate specificity of
      ubiquitin C-terminal hydrolases for ubiquitin chains.
AB  - UCHs [Ub (ubiquitin) C-terminal hydrolases] are a family of deubiquitinating
      enzymes that are often thought to only remove small C-terminal peptide tails from
      Ub adducts. Among the four UCHs identified to date, neither UCH-L3 nor UCH-L1 can
      catalyse the hydrolysis of isopeptide Ub chains, but UCH-L5 can when it is
      present in the PA700 complex of the proteasome. In the present paper, we report
      that the UCH domain of UCH-L5, different from UCH-L1 and UCH-L3, by itself can
      process the K48-diUb (Lys48-linked di-ubiquitin) substrate by cleaving the
      isopeptide bond between two Ub units. The catalytic specificity of the four UCHs
      is dependent on the length of the active-site crossover loop. The UCH domain with
      a long crossover loop (usually >14 residues), such as that of UCH-L5 or BAP1
      [BRCA1 (breast cancer early-onset 1)-associated protein 1], is able to cleave
      both small and large Ub derivatives, whereas the one with a short loop can only
      process small Ub derivatives. We also found that elongation of the crossover loop
      enables UCH-L1 to have isopeptidase activity for K48-diUb in a length-dependent
      manner. Thus the loop length of UCHs defines their substrate specificity for diUb
      chains, suggesting that the chain flexibility of the crossover loop plays an
      important role in determining its catalytic activity and substrate specificity
      for cleaving isopeptide Ub chains.

PMID- 21851342
TI  - Appropriate length of epidural catheter in the epidural space for postoperative
      analgesia: evaluation by epidurography.
AB  - In current practice, the length of epidural catheter that should be left in the
      epidural space is not standardised for effective postoperative analgesia. This
      prospective, randomised, double-blinded study aimed to determine the most
      appropriate length of epidural catheter that should be inserted into the epidural
      space for postoperative analgesia. We recruited 102 women and assigned them into
      three study groups (3, 5 and 7 cm insertion). An epidural catheter was inserted
      and epidurography was performed. Postoperatively, mean pain scores, motor and
      sensory levels, and any complications associated with the epidural catheter were
      recorded. No statistically significant difference for mean postoperative pain
      score was found at all study timings. Motor and sensory blockade was also
      statistically insignificant. Unilateral sensory analgesia developed in one
      patient in the 7 cm group and epidural catheter dislodgement was observed in four
      patients in the 3 cm group. In order to minimise catheter-related complications
      for postoperative analgesia, the most appropriate length that an epidural
      catheter should be left in the epidural space is 5 cm. You can respond to this
      article at http://www.anaesthesiacorrespondence.com.

PMID- 21851341
TI  - Selection of non-competitive leptin antagonists using a random nanobody-based
      approach.
AB  - The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the
      body's metabolism to high-energy consuming processes such as reproduction and
      immune responses. Accumulating evidence suggests that leptin plays a role in
      human pathologies, such as autoimmune diseases and cancer, thus providing a
      rationale for the development of leptin antagonists. In the present study, we
      generated and evaluated a panel of neutralizing nanobodies targeting the LR
      (leptin receptor). A nanobody comprises the variable domain of the naturally
      occurring single-chain antibodies found in members of the Camelidae family. We
      identified three classes of neutralizing nanobodies targeting different LR
      subdomains: i.e. the CRH2 (cytokine receptor homology 2), Ig-like and FNIII
      (fibronectin type III) domains. Only nanobodies directed against the CRH2 domain
      inhibited leptin binding. We could show that a nanobody that targets the Ig-like
      domain potently interfered with leptin-dependent regulation of hypothalamic NPY
      (neuropeptide Y) expression. As a consequence, daily intraperitoneal injection
      increased body weight, body fat content, food intake, liver size and serum
      insulin levels. All of these characteristics resemble the phenotype of leptin and
      LR-deficient animals. The results of the present study support proposed models of
      the activated LR complex, and demonstrate that it is possible to block LR
      signalling without affecting ligand binding. These nanobodies form new tools to
      study the mechanisms of BBB (blood-brain barrier) leptin transport and the effect
      of LR inhibition in disease models.

PMID- 21851343
TI  - Clinical evaluation of stethoscope-guided inflation of tracheal tube cuffs.
AB  - Tracheal tube cuffs are commonly inflated to pressures exceeding the recommended
      upper limit of 30 cmH(2)O. We evaluated whether a stethoscope-guided method of
      cuff inflation results in pressures within the recommended range. Patients were
      randomly assigned to receive one of two methods of cuff inflation. In the
      standard 'just seal' group, air was introduced into the tracheal cuff until the
      audible leak at the mouth disappeared. In the stethoscope-guided group, air was
      introduced into the cuff until a change from harsh to soft breath sounds
      occurred, whilst listening with a stethoscope bell placed over the thyroid
      cartilage. Twenty-five patients were recruited to each group. The median (IQR
      [range]) cuff pressure in the 'just seal' group was 34 (28-40 [18-49]) cmH(2)O,
      and in the stethoscope-guided group was 20 (20-26 [16-28]) cmH(2)O, p < 0.0001.
      The stethoscope-guided method of tracheal tube cuff inflation is a novel, simple
      technique that reliably results in acceptable tracheal cuff pressures.

PMID- 21851344
TI  - Clinically relevant asymmetry of bispectral index during recovery from
      anaesthesia for ear-nose-throat surgery in adults and children.
AB  - This study investigates the incidence of clinically relevant asymmetry in
      bispectral index readings from different sides of the skull (using two monitors)
      during ear-nose-throat surgery in 42 adults and 46 children. A unilateral
      increase or decrease > 10% from baseline was defined as an 'asymmetry'. Asymmetry
      followed by movement after stimulation was defined as a 'clinically relevant
      asymmetry'. Asymmetry occurred in 39 out of 42 adults (93%) and in 20 out of 46
      children (44%) during surgery and in 24 out of 42 adults (57%) and in 17 out of
      46 children (37%) during recovery. Clinically relevant asymmetry was observed in
      5 out of 42 adults (12%) and 6 out of 46 children (13%). The incidence of
      asymmetry was higher in adults during surgery (p = 0.0002). In conclusion,
      clinically relevant bispectral index asymmetry has been observed in > 10% of
      paediatric and adult anaesthesia and may have clinical implications. You can
      respond to this article at http://www.anaesthesiacorrespondence.com.

PMID- 21851345
TI  - Anaesthesia for 1131 patients undergoing proximal femoral fracture repair: a
      retrospective, observational study of effects on blood pressure, fluid
      administration and perioperative anaemia.
AB  - Intra-operative hypotension is a frequent occurrence during anaesthesia for hip
      fracture surgery in older patients with co-morbidities. We analysed retrospective
      data from the Brighton Hip Fracture Database to determine the intra-operative
      fall in systolic blood pressure, and the incidence of absolute (lowest systolic
      blood pressure < 90 mmHg) and relative (> 20% fall in systolic blood pressure
      from baseline) hypotension during general or spinal anaesthesia among 1131 non
      consecutive patients with hip fracture. General anaesthesia for 489 patients
      (43.2%) produced a greater mean (SD) fall in systolic blood pressure than spinal
      anaesthesia for 578 patients (51.1%): 34.2% (13.0%) vs 29.7% (10.8%),
      respectively (p < 0.0001), mean difference 4.5% (95% CI 3.1-5.9%), and was
      associated with greater mean (SD) intra-operative fluid administration (1555
      (801) ml vs 1375 (621) ml, respectively, p < 0.0001). We observed a correlation
      between the volume of subarachnoid hyperbaric bupivacaine 0.5% and fall in
      systolic blood pressure (p = 0.004): compared with patients receiving > 1.5 ml (n
      = 463), fewer patients receiving <= 1.5 ml bupivacaine 0.5% (n = 97) experienced
      episodes of absolute (31.1% vs 11.3%, p < 0.0001) or relative (83.9% vs 26.8%, p
      < 0.0001) hypotension. Both mean (SD) intravenous fluid administration (1097 ml
      (439) vs 1431 ml (638), p < 0.0001) and mean peri-operative fall in haemoglobin
      concentration (2.1 (1.8) g.dl(-1) vs 2.6 (1.7) g.dl(-1), p = 0.009) were lower in
      the low-dose spinal group. If these data are confirmed by other researchers,
      intra-operative hypotension (and consequent haemodilution secondary to reactive
      fluid administration) in this patient group may be reduced by the simple
      expedient of administering more cautious general anaesthesia, or reduced volumes
      of subarachnoid local anaesthetic.

PMID- 21851346
TI  - Studies on the spread of local anaesthetic solution in transversus abdominis
      plane blocks.
AB  - The extent of analgesia provided by transversus abdominis plane blocks depends
      upon the site of injection and pattern of spread within the plane. There are
      currently a number of ultrasound-guided approaches in use, including an anterior
      oblique-subcostal approach, a mid-axillary approach and a more recently proposed
      posterior approach. We wished to determine whether the site of injection of local
      anaesthetic into the transversus abdominis plane affects the spread of the local
      anaesthetic within that plane, by studying the spread of a local anaesthetic and
      contrast solution in four groups of volunteers. The first group underwent the
      classical landmark-based transversus abdominis plane block whereby two different
      volumes of injectate were studied: 0.3 ml.kg(-1) vs 0.6 ml.kg(-1). The second
      group underwent transversus abdominis plane block using the anterior subcostal
      approach. The third group underwent transversus abdominis plane block using the
      mid-axillary approach. The fourth group underwent transversus abdominis plane
      block using the posterior approach, in which local anaesthetic was deposited
      close to the antero-lateral border of the quadratus lumborum. All volunteers
      subsequently underwent magnetic resonance imaging at 1, 2 and 4 h following each
      block to determine the spread of local anaesthetic over time. The studies
      demonstrated that the anterior subcostal and mid-axillary ultrasound approaches
      resulted in a predominantly anterior spread of the contrast solution within the
      transversus abdominis plane and relatively little posterior spread. There was no
      spread to the paravertebral space with the anterior subcostal approach. The mid
      axillary transversus abdominis plane block gave faint contrast enhancement in the
      paravertebral space at T12-L2. In contrast, the posterior approaches, using both
      landmark and ultrasound identifications, resulted in predominantly posterior
      spread of contrast around the quadratus lumborum to the paravertebral space from
      T5 to L1 vertebral levels. We concluded that the pattern of spread of local
      anaesthetic differs depending on the site of injection into the transversus
      abdominis plane. This may have important implications for the extent of analgesia
      produced with each approach.

PMID- 21851348
TI  - Chewing abilities of elderly populations in Europe.
AB  - PURPOSE: To describe variations in chewing abilities of elderly populations in
      different European countries. METHODS: We used data from the Survey of Health,
      Ageing, and Retirement in Europe (SHARE Wave 2) and estimated a series of
      multivariate logistic regression models in order to analyse variations in self
      reported ability to bite and chew on hard foods by persons aged 50+ from 14
      European countries (P < 0.05). RESULTS: Abilities to bite and chew on hard foods
      are comparably high in Sweden, Switzerland and the Netherlands but comparably low
      in Spain, Denmark, France, Greece, Belgium, Italy, Czechia, and Poland. Median
      levels are observed in Austria, Germany, and Ireland. CONCLUSIONS: The best
      chewing abilities seem to exist amongst elderly populations in Sweden,
      Switzerland, and the Netherlands but comparably low chewing abilities appear to
      prevail amongst those in Spain, Denmark, France, Greece, Belgium, Italy, Czechia,
      and Poland. Future research is encouraged to identify the exact causes and
      consequences of such disparities in oral health.

PMID- 21851349
TI  - Extent and quality of systematic review evidence related to minimum intervention
      in dentistry: essential oils, powered toothbrushes, triclosan, xylitol.
AB  - OBJECTIVE: To investigate extent and quality of current systematic review
      evidence regarding: powered toothbrushes, triclosan toothpaste, essential oil
      mouthwashes, xylitol chewing gum. METHODS: Five databases were searched for
      systematic reviews until 13 November 2010. INCLUSION CRITERIA: relevant to topic,
      systematic review according to title and/or abstract, published in English.
      Article exclusion criteria were based on QUOROM recommendations for the reporting
      of systematic review methods. Systematic review quality was judged using the
      AMSTAR tool. All trials included by reviews were assessed for selection bias.
      RESULTS: 119 articles were found, of which 11 systematic reviews were included.
      Of these, six were excluded and five accepted: one for triclosan toothpaste; one
      for xylitol chewing gum; two for powered toothbrushes; one for essential oil
      mouthwashes. AMSTAR scores: triclosan toothpaste 7; powered toothbrushes 9 and
      11; xylitol chewing gum 9; essential oil mouthwashes 8. In total, 75 (out of 76)
      reviewed trials were identified. In-depth assessment showed a high risk of
      selection bias for all trials. CONCLUSIONS: The extent of available systematic
      review evidence is low. Although the few identified systematic reviews could be
      rated as of medium and high quality, the validity of their conclusions needs to
      be treated with caution, owing to high risk of selection bias in the reviewed
      trials. High quality randomised control trials are needed in order to provide
      convincing evidence regarding true clinical efficacy.

PMID- 21851350
TI  - The influence of practitioner nationality, experience, and sex in shaping patient
      preferences for dentists.
AB  - The present study examined patient preference for dentists as a function of the
      latter's demographics and experience. A sample of 161 British participants
      completed a questionnaire in which they were asked to rate eight dentists
      differentiated by nationality (British vs. Eastern European), sex (male vs.
      female), and experience (great vs. moderate). A mixed-design analysis of variance
      showed that there were main effects of dentist nationality (British preferred
      over Eastern European), sex (female over male), and experience (great over
      moderate). There were also a number of significant two- and three-way
      interactions, although the effect sizes of these interactions were relatively
      small. Participant sex generally did not have an impact on preferences. These
      results are discussed in relation to the extant literature on patient preferences
      for different types of health care practitioners.

PMID- 21851351
TI  - Reasons for extraction in a group of Libyan patients.
AB  - AIMS AND OBJECTIVES: To investigate the pattern and causes of tooth loss in
      patients among eastern part of Libya. MATERIALS AND METHODS: This study carried
      out at Faculty of Dentistry, Garyounis University, Benghazi, Libya. The out
      patients undergoing extractions at the Oral Surgery Department were randomly
      selected for this study between Jan 2007 and March 2008 where a total of 9,570
      extractions were performed on 8,514 patients. The incidence and reasons for tooth
      extraction, their distribution according to age and sex were studied. RESULTS:
      Males had more teeth extracted than females. Forty patients had one or more
      systemic illnesses, 34 were on regular medication. The study revealed two major
      causes of tooth loss: dental caries (55.90%) and periodontal diseases (34.42%).
      Other important causes were trauma (3.76%), impaction (1.83%), prosthodontic
      reasons (2.19%), and orthodontic reasons (1.30%) and others which included
      extraction where the tooth was associated with a tumour, cyst or supernumerary
      tooth (1.61%). Dental caries was the main causes of tooth loss during the 2nd,
      3rd and 4th decades. While periodontal diseases were the prevalent aetiological
      factor during the 4th, 5th, 6th and 7th decades of life. The posterior teeth most
      frequently extracted due to dental caries were lower first molars (43.92%).
      Whereas anterior teeth were more frequently extracted due to periodontal diseases
      (28%) with the remaining posterior teeth also being extracted (7%).

PMID- 21851352
TI  - Self medication for oral health problems in Cameroon.
AB  - OBJECTIVE: To assess the use of self medication in oral health problems in
      Cameroon. METHODS: This multi-regional cross-sectional survey was conducted in
      three towns; Bamenda, Yaounde and Buea over a 10 month period. The questionnaire
      elicited information on demography, oral problem for self medication, substance
      used for self medication, source of the substance, duration of self medication,
      reason for self medication, source of advice of the drugs or those products used,
      opinion about the substance, effect and duration. RESULTS: The prevalence of self
      medication for oral health problems was 67.8% which was significantly associated
      with age, marital status and location. The most frequently self medicated oral
      health problem was toothache (54.7%). The majority (64.5%) of the respondents
      used pharmaceutical products while a minority (7.7%) used dangerous substances
      such as petrol and vinegar for self medication. Sources of substances of self
      medication included pharmacy (55.6%), road side vendors (26.1%), native healers
      (7.8%), mobile drug vendors in buses (5.3%), and others (5.3%). The choice of
      substances used for self medication was mostly guided by the advice from
      relatives. CONCLUSION: The majority of the respondents self-medicated for oral
      health problems. Unmarried, urban residents, aged 21-30 years reported
      significantly increased self-medication for oral health problems. Evidently
      dangerous substances were utilised for self-medication in this study,
      necessitating awareness and other forms of intervention.

PMID- 21851353
TI  - In vivo remineralising effect of GC tooth mousse on early dental enamel lesions:
      SEM analysis.
AB  - OBJECTIVE: Casein phosphopeptide-amorphous calcium phosphate nanocomplexes (CPP
      ACP) exhibit anticariogenic potential in laboratory, animal and human
      experiments. The remineralising potential of synthetic CPPs on early enamel
      caries was investigated. DESIGN: In vivo study. SETTING: University of Naples
      'Federico II', School of Dentistry, Department of Paediatric Dentistry, 2010,
      Italy. PARTICIPANTS: 40 volunteers (age range 10-16 years) were recruited and
      divided in two groups of 20 (Group A and B). INTERVENTIONS: In Group A subjects
      two demineralised enamel specimens were placed on the buccal surfaces of the
      first molars and subjects were instructed to apply a commercial product
      containing CPPs (GC Tooth Mousse) only on the right-sided specimen and a placebo
      mousse on the left, for 1 month. In Group B subjects two enamel specimens were
      similarly placed into the mouth and used as controls. RESULTS: SEM analysis
      revealed a diffuse and homogeneous mineral coating, reducing the surface
      alterations only in the demineralised specimens treated with synthetic CPPs into
      the mouth. CONCLUSIONS: Results demonstrate that CPPs are able to promote
      remineralisation of early enamel lesions.

PMID- 21851354
TI  - Prevalence and severity of dental caries in Libyan schoolchildren.
AB  - OBJECTIVES: To assess prevalence and severity of dental caries, examine gender
      differences and assess the relationship of dental caries to socioeconomic status
      in a group of Libyan schoolchildren. DESIGN AND SETTING: A cross sectional
      observational study with cluster sampling within schools. PARTICIPANTS: A random
      sample of 791, 12-year-olds in 36 elementary public schools in Benghazi. METHODS
      AND MAIN OUTCOME MEASURES: Dental caries was assessed using the DMFT and DMFS
      indices and WHO (1997) criteria. Information about socioeconomic status was
      collected through a dental health questionnaire. RESULTS: The prevalence of
      dental caries was 57.8%. The mean DMFT and DMFS indices were 1.68 (SD +/- 1.86)
      and 2.39 (SD +/- 3.05) for all subjects and 2.90 (SD +/- 1.56) and 4.14 (SD +/-
      2.97) for subjects with caries experience. Dental caries was more prevalent
      amongst girls (P = 0.002). There was a statistically significantly negative
      association between dental caries and the level of father's education (P =
      0.015). CONCLUSIONS: While dental caries prevalence in 12 year-old Libyan
      children was high, the mean DMFT was low compared with other developing
      countries, but higher than the WHO goal for year 2020. The high level of
      untreated caries is a cause for concern, representing a high unmet treatment
      need.

PMID- 21851355
TI  - International migration of Lithuanian oral health professionals: a survey of
      graduates.
AB  - AIM: To assess the intentions of general dentists, dental specialists, dental
      hygienists, assistants and technicians graduated from Lithuanian educational
      institutions in 0032010 to engage in practice in foreign countries. MATERIAL AND
      METHODS: A questionnaire survey was carried out among all graduates (N = 347)
      general dentists, dental specialists, dental hygienists, assistants and
      technicians in Lithuania in 2010. The response rate was 82.7%. RESULTS: 32.4% of
      graduates from all oral health specialties mentioned their intentions to emigrate
      from Lithuania. The highest rate of emigration intentions was found among dental
      assistants (35.5%) and general dentistry graduates (26.9%). Factors related to
      higher reported intentions to emigrate were relatives or friends residing in
      other states, self-rating of personal unhappiness, or residing in large cities.
      As many as every fourth (23.1%) dental hygienist, assistant and technician
      graduates had already planned, arranged and organised for emigration. Major
      destination countries are the UK, Ireland, Norway and Sweden. Of all oral health
      professionals, the highest rate of reported intentions to emigrate was among
      dental hygienists, assistants and technicians, therefore many of them will not
      join the professional community in Lithuania. CONCLUSION: The survey gives
      indications about the possible magnitude of emigration of oral health
      professionals from Lithuania and is the first study of its kind. The results show
      that Lithuania is a major sending country in the context of international oral
      health professionals' migration flows.

PMID- 21851356
TI  - Oral health status, salivary factors and microbial analysis in patients with
      active gastro-oesophageal reflux disease.
AB  - AIM: To present a complex oral health status including salivary factors,
      microbial analysis and periodontal and hygiene indices in patients with active
      gastro-oesophageal reflux disease (GORD). Return of stomach contents is quite
      common in cases of gastro-oesophageal reflux. Pathological acid movement from the
      stomach into the oesophagus and oral cavity may lead to a development of dental
      erosion. Long-lasting untreated GORD may damage hard dental and periodontal
      tissues and alter the oral microbial environment. The quality and amount of the
      saliva play an important role in hard and soft oral tissues changes. METHOD:
      Fifty patients with diagnosed GORD using 24-hour pH manometry underwent dental
      examination; 24 patients had active GORD and had been waiting for surgical
      therapy. In this patient group oral health status and salivary analysis were
      evaluated. RESULTS: Indicated low salivary flow rates and buffering capacity with
      a low caries risk but a high risk for dental erosion progression.

PMID- 21851357
TI  - Dental indices must not be CAST in stone.

PMID- 21851359
TI  - Effects of stomatal delays on the economics of leaf gas exchange under
      intermittent light regimes.
AB  - * Understory plants are subjected to highly intermittent light availability and
      their leaf gas exchanges are mediated by delayed responses of stomata and leaf
      biochemistry to light fluctuations. In this article, the patterns in stomatal
      delays across biomes and plant functional types were studied and their effects on
      leaf carbon gains and water losses were quantified. * A database of more than 60
      published datasets on stomatal responses to light fluctuations was assembled. To
      interpret these experimental observations, a leaf gas exchange model was
      developed and coupled to a novel formulation of stomatal movement energetics. The
      model was used to test whether stomatal delays optimize light capture for
      photosynthesis, whilst limiting transpiration and carbon costs for stomatal
      movement. * The data analysis showed that stomatal opening and closing delays
      occurred over a limited range of values and were strongly correlated. Plant
      functional type and climate were the most important drivers of stomatal delays,
      with faster responses in graminoids and species from dry climates. * Although
      perfectly tracking stomata would maximize photosynthesis and minimize
      transpiration at the expense of large opening costs, the observed combinations of
      opening and closure times appeared to be consistent with a near-optimal balance
      of carbon gain, water loss and movement costs.

PMID- 21851360
TI  - The diel imprint of leaf metabolism on the delta13 C signal of soil respiration
      under control and drought conditions.
AB  - Recent (13) CO(2) canopy pulse chase labeling studies revealed that
      photosynthesis influences the carbon isotopic composition of soil respired CO(2)
      (delta(13) C(SR)) even on a diel timescale. However, the driving mechanisms
      underlying these short-term responses remain unclear, in particular under drought
      conditions. The gas exchange of CO(2) isotopes of canopy and soil was monitored
      in drought/nondrought-stressed beech (Fagus sylvatica) saplings after (13) CO(2)
      canopy pulse labeling. A combined canopy/soil chamber system with gas-tight
      separated soil and canopy compartments was coupled to a laser spectrometer
      measuring mixing ratios and isotopic composition of CO(2) in air at high temporal
      resolution. The measured delta(13) C(SR) signal was then explained and
      substantiated by a mechanistic carbon allocation model. Leaf metabolism had a
      strong imprint on diel cycles in control plants, as a result of an alternating
      substrate supply switching between sugar and transient starch. By contrast, diel
      cycles in drought-stressed plants were determined by the relative contributions
      of autotrophic and heterotrophic respiration throughout the day. Drought reduced
      the speed of the link between photosynthesis and soil respiration by a factor of
      c. 2.5, depending on the photosynthetic rate. Drought slows the coupling between
      photosynthesis and soil respiration and alters the underlying mechanism causing
      diel variations of delta(13) C(SR).

PMID- 21851361
TI  - Contact allergy and allergic contact dermatitis in children - a review of current
      data.
AB  - Allergic contact dermatitis (ACD) in children was previously considered to be a
      rare occurrence. However, the growing number of case reports and cross-sectional
      studies through the past three decades indicate that ACD is, in fact, a highly
      relevant diagnosis in children. Furthermore, the frequency of ACD in children
      seems to be increasing. In 1999, a review of the literature reported prevalence
      rates of 14.5-70% in selected paediatric populations. The current paper reviews
      the studies on the prevalence of positive patch test reactions and ACD in the
      paediatric population during the past decade, and provides an overview of the
      main findings. We found reported sensitization rates of 26.6-95.6% in selected
      groups of children. The associated relevance was 51.7-100%. The most common
      allergens were nickel, cobalt, thimerosal, and fragrance. Tailored patch testing
      increases the rate of relevant patch test reactions. Children with atopic
      dermatitis are as frequently sensitized as children with no history of atopic
      dermatitis, and there are no differences associated with sex. Children and adults
      can be tested with equal concentrations of patch test allergens. Our findings may
      support the notion that the prevalence of ACD in children is increasing over time
      or indicate an increased awareness.

PMID- 21851363
TI  - Polymorphisms of innate immunity receptors in infection by parasites.
AB  - The innate immune system is the first line of defence against infection by
      pathogenic bacteria, virus and parasites and is also responsible for initiating
      an adaptive immune response. In contrast to the receptors of adaptive immunity
      (TCRs and antibodies) which are generated by gene recombination, receptors of the
      innate immune system are encoded in the germline and are thus inherited from
      generation to generation. Although evolutionarily selected, the genes encoding
      the innate recognition receptors show variations among individuals, and these
      polymorphisms may have an impact on the ability of an individual to deal with an
      infection. In recent years, several polymorphisms have been identified in innate
      recognition receptors, and efforts are being made to determine whether these
      polymorphisms are associated with a higher or lower susceptibility to infectious
      diseases. These studies will allow a better understanding of the role of innate
      receptors in specific diseases and are valuable in the design of preventive or
      therapeutic interventions to fight the disease. In this review, we summarize
      studies aimed at determining the influence of polymorphisms in innate recognition
      receptors on the susceptibility to diseases caused by parasites.

PMID- 21851362
TI  - Anisakis hypersensitivity in Italy: prevalence and clinical features: a
      multicenter study.
AB  - BACKGROUND: Anisakis simplex (As), a parasite in fish, is able to sensitize
      humans via the alimentary tract. The prevalence of hypersensitivity and allergy
      to As outside the Iberian peninsula has not been investigated so far. We
      investigated Anisakis hypersensitivity in different areas of Italy. METHODS:
      Consecutive subjects seen at 34 Italian allergy centers from October to December
      2010 were investigated both by specific interview and by skin prick test (SPT)
      with As extract. RESULTS: A total of 10 570 subjects were screened, of which 474
      (4.5%) scored positive on Anisakis SPT and 66 of these (14% of those sensitized;
      0.6% of the studied population) had a history of As allergy. Marinated anchovies
      were the most frequent cause of allergic reactions. Thirty-four (52%) patients
      were mono-sensitized to Anisakis. Sensitization rate showed marked geographic
      differences (range: 0.4-12.7%), being highest along the Adriatic and Tyrrhenian
      coasts, where homemade marinated anchovies are an age-old tradition. In inland
      centers in northern Italy, the prevalence was directly related to the number of
      inhabitants. The analysis of the impact of immigration on the prevalence of
      Anisakis hypersensitivity showed that about 60% of sensitized subjects in Milano
      and Torino came from southern Italy or from non-European countries. CONCLUSIONS:
      Anisakis hypersensitivity and allergy are mainly a matter of dietary habits.
      Areas where marinated anchovies are popular can be considered as 'endemic' for
      this type of food allergy, whereas immigration and, possibly, new or imported
      trendy food styles, such as eating raw fish carpaccios or sushi, are a major
      causative factor in big cities of inland zones.

PMID- 21851364
TI  - Enrichment of invariant natural killer T cells in the bone marrow of visceral
      leishmaniasis patients.
AB  - Lipid antigens of Leishmania donovani like lipophosphoglycans are shown as a
      potent ligand for the activation of invariant natural killer T (iNKT) cells. It
      is reported that activation of iNKT cells augments the disease pathology in
      experimental visceral leishmaniasis (VL). In this study, we demonstrate the
      enrichment of iNKT cells in the bone marrow, one of the disease sites among
      patients with VL.

PMID- 21851365
TI  - Cerebral malaria protection in mice by species-specific Plasmodium coinfection is
      associated with reduced CC chemokine levels in the brain.
AB  - Cerebral malaria is a major pathological complication of Plasmodium falciparum
      infection in humans. Epidemiological observations have suggested that the
      clinical evolution of P. falciparum infections may be influenced by the
      concurrent presence of another Plasmodium species. Infection of susceptible mouse
      strains with P. berghei ANKA (PbA) provides an experimental model of cerebral
      malaria which has been extensively used to identify different components of the
      immune system involved in cerebral malaria. This model has also been employed to
      investigate the influence of experimental mixed-Plasmodium-species infections on
      the expression of cerebral malaria; PbA-induced cerebral malaria is completely
      inhibited by the simultaneous presence of P. yoelii yoelii 17 X clone 1.1
      parasites, and accumulation of CD8(+) T cells in the brain vasculature is
      abolished. We investigated whether brain levels of CD8(+) -T-cell-chemoattractant
      chemokines CCL3, CCL4 and CCL5 are reduced in these protected coinfected mice
      compared with PbA-infected mice. Coinfected mice were found to exhibit
      significantly reduced levels of all three chemokines on day 6 post-infection.
      This finding may contribute to the abolition of the accumulation of CD8(+) T
      cells in the brain vasculature and the prevention of the development of cerebral
      malaria in coinfected mice.

PMID- 21851367
TI  - Root canal treatment of a periradicular lesion caused by unintentional root
      damage after orthodontic miniscrew placement: a case report.
AB  - AIM: To present the successful endodontic management of a maxillary lateral
      incisor tooth with a periradicular lesion caused by unintentional root damage
      after orthodontic miniscrew placement. SUMMARY: A 22-year-old female was
      diagnosed with a skeletal Class II, Division 2 malocclusion with Class II molar
      and canine relationships on both sides. The treatment plan included distalization
      of the maxillary first molars bilaterally followed by full fixed appliance
      therapy. For the maxillary molar distalization, an appliance in conjunction with
      a miniscrew anchorage system was designed. Two months later, the patient came to
      the clinic with complaints of pain in the maxillary right lateral incisor region.
      On intraoral examination, intraoral sinus tracts were detected in the maxillary
      right buccal sulcus and palate. A large radiolucent lesion with a well-defined
      margin around the root of the maxillary right lateral incisor was seen. Root
      canal treatment was performed on the maxillary right lateral incisor tooth. The
      root canal was filled with gutta-percha and AH Plus sealer, using a lateral
      compaction technique. The final restoration of the tooth was completed using
      composite, and the tooth was reviewed after 10 months. The tooth was asymptomatic
      and radiographically showed repair of the lesion. Healing was achieved without
      any need for further endodontic or surgical intervention. Key learning points *
      This case illustrates the need to take care with miniscrews when performing
      orthodontic treatment, especially when the miniscrews are in close proximity to
      root apices. * The periradicular lesion as a result of miniscrew damage was
      successfully treated with root canal treatment.

PMID- 21851366
TI  - Preliminary evaluation of a novel polymer nanocomposite as a root-end filling
      material.
AB  - AIM: To evaluate two nanoparticle-enhanced polymer root-end filling materials
      (NERP1 and NERP2) on the initial apical seal as compared to a polymer-based
      commercial compomer. METHODOLOGY: One hundred and forty extracted roots with
      completely formed apices were resected 3 mm from the apex. Cavities were then
      prepared in the apical openings of the resected root ends using an ultrasonic
      handpiece to a depth of 3 mm. The roots were then randomly divided into five
      groups to receive one of five root-end filling materials. Roots in groups 1 and 2
      received NERP1 and NERP2, whilst those in groups 3 and 4 received identical
      polymers as groups 1 and 2 but without nanoparticle addition (RP1 and RP2,
      respectively). The root-end cavities for the fifth group were filled with
      commercially available root-end filling compomer. Roots were mounted in a dual
      chamber leakage apparatus and inoculated coronally with Enterococcus faecalis.
      Turbidity of the apical broth was assessed daily for 4 weeks as a sign of initial
      leakage. The results were statistically analysed using odds ratio and Fisher's
      chi-square analysis. RESULTS: Nanoparticle-enhanced root-end filling polymer 1
      displayed significantly fewer leaked samples compared to all other tested groups
      as early as 5 days, whilst NERP2 was not significantly different compared to
      other groups. Odds ratio analysis revealed leakage of the commercial compomer was
      12 times more likely than NERP1. CONCLUSION: Nanoparticle-enhanced root-end
      filling polymer 1 can reduce apical microleakage significantly under laboratory
      conditions.

PMID- 21851368
TI  - Initial fibroblast attachment to Erbium:YAG laser-irradiated dentine.
AB  - AIMS: To evaluate the effects of Erbium (Er):YAG laser irradiation on the
      morphology of resected dentine surfaces, and to investigate fibroblast attachment
      to laser-irradiated dentine surfaces. METHODOLOGY: Dentine blocks obtained from
      single-rooted human teeth were divided into the following groups after
      sterilization in an autoclave: (i) Laser group treated with Er:YAG laser
      irradiation (30 mJ per pulse, 10 pps, 60 s); (ii) L-MTAD group treated with laser
      irradiation as in (i) plus a mixture of doxycycline, tetracycline isomer and
      citric acid; (iii) RC-Prep group treated with EDTA gel or cream (RC-Prep) and
      (iv) Control group left untreated. After each treatment, the dentine blocks were
      incubated with NIH/3T3 fibroblasts cultured to subconfluency in Dulbecco's
      modified Eagle's medium supplemented with 10% foetal bovine serum and
      antibiotics. The number of attached cells amongst the groups was analysed
      statistically at the 5% significance level. The dentine surface morphologies and
      cell attachments were evaluated by counting assays, histological observations and
      scanning electron microscopy (SEM). RESULTS: The number of attached cells was
      significantly higher (P < 0.05) in the Laser group than in the RC-Prep and
      Control groups at 16 h. Dendritic cell extension of the fibroblasts was only
      observed in the Laser group at 8 h by SEM. In the histological analyses,
      significantly more attached cells were found on the dentine surfaces treated with
      laser irradiation. CONCLUSIONS: Er:YAG laser irradiation induced morphological
      alterations in dentine surfaces, which may improve the attachment of fibroblasts
      to dentine.

PMID- 21851369
TI  - Radiofrequency ablation of accessory pathways in children and congenital heart
      disease patients: impact of a nonfluoroscopic navigation system.
AB  - BACKGROUND: We sought to assess the impact of routine use of a nonfluoroscopic
      navigation system in the procedural aspects of radiofrequency ablation of
      accessory pathways (APs) in pediatric and congenital heart disease (CHD) patients
      and the reduction of fluoroscopy in different pathway locations. METHODS: This
      was a retrospective review of 192 patients, divided in two groups: group A (76
      patients, fluoroscopic only ablation) and group B (116 patients, combined use of
      fluoroscopy and a nonfluoroscopic system (NavXTM). Comparison of procedural
      aspects (procedure time, fluoroscopy time, success, complications, and
      recurrences) was performed. RESULTS: The two groups were comparable in terms of
      age, AP location, and presence of CHD. The mean age was 11.34 +/- 4.65 years in
      group A versus 10.91 +/- 3.68 years in group B. The procedure duration was
      significantly shorter in group B than in group A (177.06 +/- 62.18 vs 242.45 +/-
      99.07) (P < 0.001). There was a significant reduction in the fluoroscopy time in
      group B compared to group A (8.27 +/- 8.23 vs 39.77 +/- 32.65 minutes) (P <
      0.001). The difference between the two groups was statistically significant in
      all categories of APs. The success rate was 97.4% in group A and 96.6% in group
      B. There were no complications directly related to the use of the nonfluoroscopic
      system. There was no difference in the recurrence rate. CONCLUSIONS: The use of a
      nonfluoroscopic system for catheter navigation resulted in significant reduction
      of total procedure and fluoroscopy time during catheter ablation of APs in
      pediatric and CHD patients, regardless of the location of the pathway, without a
      compromise in safety and efficacy.

PMID- 21851370
TI  - Mycophenolate mofetil for patients with autoimmune hepatitis and overlap
      syndromes.

PMID- 21851372
TI  - Review article: pancreatic renin-angiotensin systems in health and disease.
AB  - BACKGROUND: In addition to the circulating (endocrine) renin-angiotensin system
      (RAS), local renin-angiotensin systems are now known to exist in diverse cells
      and tissues. Amongst these, pancreatic renin-angiotensin systems have recently
      been identified and may play roles in the physiological regulation of pancreatic
      function, as well as being implicated in the pathogenesis of pancreatic diseases
      including diabetes, pancreatitis and pancreatic cancer. AIM: To review and
      summarise current knowledge of pancreatic renin-angiotensin systems. METHODS: We
      performed an extensive PubMed, Medline and online review of all relevant
      literature. RESULTS: Pancreatic RAS appear to play various roles in the
      regulation of pancreatic physiology and pathophysiology. Ang II may play a role
      in the development of pancreatic ductal adenocarcinoma, via stimulation of
      angiogenesis and prevention of chemotherapy toxicity, as well as in the
      initiation and propagation of acute pancreatitis (AP); whereas, RAS antagonism is
      capable of preventing new-onset diabetes and improving glycaemic control in
      diabetic patients. Current evidence for the roles of pancreatic RAS is largely
      based upon cell and animal models, whilst definitive evidence from human studies
      remains lacking. CONCLUSIONS: The therapeutic potential for RAS antagonism, using
      cheap and widely available agents, and may be untapped and such roles are worthy
      of active investigation in diverse pancreatic disease states.

PMID- 21851373
TI  - The effect of parathyroidectomy on neuropsychological symptoms and biochemical
      parameters in patients with asymptomatic primary hyperparathyroidism.
AB  - BACKGROUND: With increased biochemical screening, primary hyperparathyroidism
      (pHPT) is often discovered incidentally whilst patients are asymptomatic.
      OBJECTIVE: To assess the impact of parathyroidectomy on neuropsychological
      symptoms and biochemical parameters in people with asymptomatic pHPT, whilst
      controlling for the surgical procedure. PATIENTS/DESIGN/MEASUREMENTS: Twenty-four
      patients with asymptomatic pHPT requiring parathyroidectomy, in accordance with
      National Institutes for Health recommendations, were recruited prospectively. A
      control group of 23 subjects was recruited simultaneously from consecutive
      patients undergoing diagnostic hemithyroidectomy (HT) for benign thyroid nodules.
      Operations were performed by a single surgeon. Biochemical investigations and
      neuropsychological symptoms were measured preoperatively and 3 months after
      surgery. Neuropsychological symptoms were measured using the Hospital Anxiety
      (HAD-A) and Depression (HAD-D) scales and the Mood Rating Scale (MRS). RESULTS:
      Postoperatively, calcium and parathyroid hormone normalized in all patients in
      the pHPT group. Patients with pHPT showed a significant improvement in
      neuropsychological symptoms with a pre- and postoperative mean change of 2.45 +/-
      2.57 (P < 0.05) on HAD-A, 2.79 +/- 3.85 (P < 0.05) on HAD-D, and 3.2 +/- 4.57 (P
      < 0.05) on MRS, parameters that were unaltered in the HT group. The differences
      between the two groups remained statistically significant after adjustment for
      age and sex for HAD-D (mean change 2.8, 95% CI = 0.3, 5.3, P = 0.025) and MRS
      (mean difference 3.5, 95% CI = 0.4, 6.7, P = 0.027) but not for HAD-A (mean
      difference 1.5, 95% CI = -0.8, 3.8, P = 0.20). For all three mental health
      scores, there were no significant associations with either age or sex.
      CONCLUSIONS: Asymptomatic pHPT is associated with neuropsychological symptoms
      that improve after parathyroidectomy.

PMID- 21851374
TI  - Congenital hyperinsulinism: marked clinical heterogeneity in siblings with
      identical mutations in the ABCC8 gene.

PMID- 21851375
TI  - The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory
      myopathies and promotes myotube survival to inflammatory stress.
AB  - AIMS: Recent studies propose the neurotrophin receptor p75NTR as a marker for
      muscle satellite cells and a key regulator of regenerative processes after
      injury. Here, we investigated the contribution of cellular compartments other
      than satellite cells and regenerating myofibres to p75NTR signal in diseased
      skeletal muscle. METHODS: We checked regulation of p75NTR expression in muscle
      biopsies from patients with inflammatory myopathies (polymyositis,
      dermatomyositis and inclusion body myositis), or Becker muscular dystrophy, and
      in nonmyopathic tissues. Quantitative PCR, immunohistochemistry,
      immunofluorescence or electron microscopy were used. RNA interference approaches
      were applied to myotubes to explore p75NTR function. RESULTS: We found p75NTR
      transcript and protein upregulation in all inflammatory myopathies but not in
      dystrophic muscle, suggesting a role for inflammatory mediators in induction of
      p75NTR expression. In inflamed muscle p75NTR was localized on distinct cell
      types, including immune cells and mature myofibres. In vitro assays on human
      myotubes confirmed that inflammatory factors such as IL-1 could induce p75NTR.
      Finally, RNA interference experiments in differentiated cells showed that, in the
      absence of p75NTR, myotubes were more susceptible to apoptosis when exposed to
      inflammatory stimuli. CONCLUSIONS: Our observations that p75NTR is upregulated on
      skeletal myofibres in inflammatory myopathies in vivo and promotes resistance to
      inflammatory mediators in vitro suggest that neurotrophin signalling through
      p75NTR may mediate a tissue-protective response to inflammation in skeletal
      myofibres.

PMID- 21851376
TI  - Impact of paediatric human immunodeficiency virus infection on children's and
      caregivers' daily functioning and well-being: a qualitative study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection impacts not only upon
      the physical health of affected children, but also their psychosocial functions,
      family relationships and economical status. Caregivers are confronted with
      complex challenges related to the physical, emotional and financial demands of
      raising these children. The purpose of this study was to enhance our
      understanding of the impact of HIV disease on both children's and caregivers'
      well-being, using a qualitative inquiry approach. METHODS: A total of 35 primary
      caregivers of HIV-infected children participated in in-depth interviews. The
      issues discussed included the major negative impacts on children's daily
      functioning and well-being, and the perceived caregiver/parental burden.
      Participants included parents (40%), grandparents (22.8%), other relatives (e.g.
      uncles, aunts) (34.3%) and one foster parent (2.8%). RESULTS: Qualitative
      analysis revealed that the major negative impacts of HIV/AIDS included physical
      symptoms, school performance and relationship changes. The major negative impacts
      on caregivers' well-being included acceptance of the diagnosis, dealing with the
      financial burden and keeping the diagnosis private. CONCLUSIONS: Approaches are
      needed to address these challenges by enhancing families' coping skills and
      building supportive networks.

PMID- 21851377
TI  - Decrease of tight junction integrity in the ipsilateral thalamus during the acute
      stage after focal infarction and ablation of the cerebral cortex in rats.
AB  - 1. Whether damage to the blood-brain barrier (BBB) occurs in remote areas after a
      focal cortical lesion remains unknown. The present study investigated tight
      junction-related proteins and tight junction microstructure in the ipsilateral
      thalamus during the acute stage after middle cerebral artery occlusion (MCAO) and
      cortical aspiration lesion (CAL) in rats. 2. Thirty-six hypertensive and
      normotensive rats were subjected to MCAO or CAL; another 18 rats in each group
      were submitted to sham operation. Zonula Occluden (ZO)-1, occludin and albumin
      were detected by western blotting 12 and 24 h after surgery. Tight junction
      microstructure was evaluated using electron microscopy, whereas albumin location
      in the ipsilateral thalamus was determined using double immunostaining for
      albumin and occludin or albumin and neuronal nuclei (NeuN) 24 h after surgery. 3.
      Twenty-four hours after MCAO or CAL, occludin expression was reduced to 78.4% and
      81.3%, respectively, compared with control. A reduction in ZO-1 expression in the
      ipsilateral thalamus (to 79%) was seen only after CAL (P < 0.05). Membrane
      contact at the tight junction was discontinuous in the ipsilateral thalamus in
      both MCAO and CAL rats. Albumin levels were 23.2% and 82.5% higher in the
      ipsilateral thalamus after MCAO and CAL, respectively (P < 0.05). The percentage
      of the albumin-positive area that coincided with the occludin-positive area in
      the MCAO and CAL groups was 76.8% and 64.6%, respectively, indicating that
      albumin was mainly localized around the microvessels. 4. The results of the
      present study suggest that tight junction integrity decreases during the acute
      stage in the ipsilateral thalamus after MCAO and CAL in rats.

PMID- 21851378
TI  - A unified pharmacokinetic approach to individualized drug dosing.

PMID- 21851379
TI  - The effects of a single nucleotide polymorphism in SLCO1B1 on the
      pharmacodynamics of pravastatin.
AB  - AIM: To determine whether the SNP rs4149056 in SLCO1B1 alters the
      pharmacodynamics of pravastatin. METHODS: rs4149056 was genotyped in 626
      pravastatin-treated participants in the WOSCOPS trial and the response after 1
      year of treatment was compared between the different genotypes. RESULTS:
      Pravastatin reduced serum LDL cholesterol by 22.2% in TT homozygotes, by 22.2% in
      TC heterozygotes and by 17.7% in CC homozygotes (TT + TC vs. CC P value 0.33).
      There were no significant differences in the response of total cholesterol, LDL,
      HDL, triglycerides or CRP to pravastatin between the genotypes. CONCLUSION: The
      rs4149056 SNP did not significantly affect the pharmacodynamics of pravastatin.

PMID- 21851380
TI  - A Steinian approach to an empathic understanding of hope among patients and
      clinicians in the culture of palliative care.
AB  - AIM: This article presents a discussion of empathy in the context of human
      person, reason and hopes in the clinical setting. BACKGROUND: Empathy was
      introduced to nursing as part of an ethical and philosophical foundation for
      caring. It helped to solve the tension and meet the demands that empathy placed
      upon nursing practice. DATA SOURCES: This article is based on two studies
      undertaken between 2008 and 2010 to understand the concept of hope and empathy
      among people with terminal cancer and doctors who care for them. Doctoral
      dissertations and theses of Edith Stein (1916-1917), Marianne Sawicki [Body, Text
      and Science. The Literary of Investigative Practices and the Phenomenology of
      Edith Stein (1997) Kluwer Academic Publisher, Dordrecht], and Sister M. Judith
      Parsons (2005) have been used to examine: 'the essence of acts of empathy', 'the
      constitution of the psycho-physical individual' and 'empathy as understanding of
      intellectual persons'. CINAHL, MEDLINE and PROQUEST have provided further
      supporting data. Discussion.  Steinian empathy requires that we use affective
      resonance, cognitive understanding and distance, as we grasp another person's
      emotional and situational reality while in the caring role as nurses.
      Implications for current nursing.  Steinian empathy is about recognizing a lived
      experience and standing side-by-side with that person. Nurses can transmit this
      knowledge to enable and support courage and wisdom to reduce feelings of
      helplessness when caring for people with terminal illness. CONCLUSION: Not only
      is empathy a safe and permissible emotion, it is the linchpin to a caring patient
      nurse relationship and we must embrace this.

PMID- 21851381
TI  - Pain descriptors for critically ill patients unable to self-report.
AB  - AIM:   To examine descriptors used by nurses in two Canadian intensive care units
      to document pain presence for critically ill patients unable to self-report.
      BACKGROUND:   Systematic documentation of pain assessment is essential for
      communication and continuity of pain management, thereby enabling better pain
      control, maximizing recovery and reducing physical and psychological sequelae.
      METHOD:   A retrospective, mixed method, having observational design in two Level
      III intensive care units of a quaternary academic centre in Toronto, Canada.
      During 2008-2009, data were abstracted via chart review guided by a reference
      compendium of potential behavioural descriptors compiled from existing
      behavioural pain assessment tools. RESULTS:   A total of 679 narrative
      descriptions were extracted. Behavioural descriptors (232, 34%), physiological
      descriptors (93, 14%), and descriptors indicating the patient was pain free (117,
      17%) were used to describe pain presence or absence. Narratives also described
      analgesia administered without descriptors of pain assessment (117, 17%) and
      assessment and analgesic administration prior to a known painful procedure (30,
      4%). Emerging themes included life-threatening treatment interference, decisional
      uncertainty and a wakefulness continuum. CONCLUSION:   Inconsistent or ambiguous
      documentation was problematic in this sample. This may reflect confounding
      behaviours and concomitant safety priorities. Developing a lexicon of pain
      assessment descriptors of critically ill patients unable to self-report for use
      in combination with valid and reliable measures may improve documentation
      facilitating appropriate analgesic management. Protocols or unit guidelines that
      prioritize a trial of analgesia before administration of sedatives may decrease
      decisional uncertainty when patients exhibit ambiguous behaviours such as
      agitation or restlessness.

PMID- 21851382
TI  - The impact of foreign caregiving on depression among older people in Taiwan:
      model testing.
AB  - AIM:   This article is a report of a study of predicting the factors that
      influence depression in the older people in Taiwan. Background.  In 1991, Taiwan
      opened the labour market to foreign caregivers for the older people who needed
      long-term care. With the differences in language, culture and lifestyle between
      foreign caregivers and older people in Taiwan, it was hypothesized that the older
      people would not be able to relate to them, and therefore become depressed.
      METHODS:   The data were collected from 116 Taiwanese older people from July to
      September, 2005. Path analysis using multiple regression analyses was conducted
      to estimate the direct and indirect effects of caregiving communication,
      activities of daily living, income and social support on depression among older
      people in Taiwan. To evaluate the hypotheses for this research, bi-variate linear
      regression and multiple regression analyses were used. RESULTS/FINDINGS:   The
      results indicated that the level of activities of daily living (beta = -0.201, P
      = 0.010), care-giving communication (beta = -0.272, P = 0.002) income (beta = 
      0.305, P = 0.000) and social support (beta = -0.276, P = 0.002) were the
      predictors of depression in older people in Taiwan. Social support was a
      mediating factor for caregiving communication and depression. Furthermore,
      foreign caregiver care was not correlated with depression among older people in
      Taiwan. CONCLUSIONS:   The findings influence the public awareness of depression
      in older people, and provide the foundational information to influence the policy
      makers of Taiwan to evaluate the foreign caregiver policy.

PMID- 21851383
TI  - The consequences of unsafe abortion: a qualitative study.
AB  - AIM:   This paper is a report of a study of the consequences of illegal abortions
      experienced by Iranian women. BACKGROUND:   Despite the increase in effective and
      safe methods of contraception and the distribution of information about these
      methods, unwanted pregnancy is still a problem in some societies. Induced
      abortion is a common procedure throughout the world and at least half of more
      than 45 million induced abortions which happen in a year are performed under
      unsafe circumstances. Unsafe abortions carry a high risk of maternal mortality
      and morbidity, accounting for more than 80,000 maternal deaths per year. METHOD: 
      In this qualitative study, 27 participants were interviewed in 2006. Some
      participants were women who had illegal abortions and others were people who had
      contact with those women. Content analysis was used to identify and categorize
      participants' responses to the interview questions. FINDINGS:   Four consequences
      of women's experiences of illegal abortion were identified: physical,
      psychological, socio-political and judicial. CONCLUSION:   In Iran, as in some
      other developing countries intentional abortion, except for some special cases,
      is illegal because of social and religious beliefs. In these countries, offering
      services and support to women with unwanted pregnancies seems to be the best
      solution for reducing or preventing illegal abortion.

PMID- 21851384
TI  - Analysis of interaction of Sendai virus V protein and melanoma differentiation
      associated gene 5.
AB  - Sendai virus (SeV), a pneumotropic virus of rodents, has an accessory protein, V,
      and the V protein has been shown to interact with MDA5, inhibiting IRF3
      activation and interferon-beta production. In the present study, interaction of
      the V protein with various IRF3-activating proteins including MDA5 was
      investigated in a co-immunoprecipitation assay. We also investigated interaction
      of mutant V proteins from SeVs of low pathogenicity with MDA5. The V protein
      interacted with at least retinoic acid inducible gene I, inhibitor of kappaB
      kinase epsilon and IRF3 other than MDA5. However, only MDA5 interacted with the V
      protein dependently on the C-terminal V unique (Vu) region, inhibiting IRF3
      reporter activation. The Vu region has been shown to be important for viral
      pathogenicity. We thus focused on interaction of the V protein with MDA5. Point
      mutations in the Vu region destabilized the V protein or abolished the
      interaction with MDA5 when the V protein was stable. The V-R320G protein was
      highly stable and interacted with MDA5, but did not inhibit activation of IRF3
      induced by MDA5. Viral pathogenicity of SeV is related to the inhibitory effect
      of the V protein on MDA5, but is not always related to the binding of V protein
      with MDA5.

PMID- 21851385
TI  - Tumor necrosis factor-alpha can induce Langhans-type multinucleated giant cell
      formation derived from myeloid dendritic cells.
AB  - The formation of the rich cellular features of MGCs, where the nuclei are
      arranged circularly at the periphery of the cell (morphologically epithelioid;
      Langhans-type), is assumed to be associated with any granulomatous disease. The
      mechanism by which TNF controls the formation of human MGCs in vitro was
      investigated, focusing on the effect of the TNF-neutralizing antibody. Peripheral
      blood monocytes were isolated with mAb-coated immunologic magnetic beads and
      cultured for 10 days in the presence of 20 ng/mL GM-CSF and 10 ng/mL IL-4. These
      cells were further incubated in the presence of TNF-alpha with/without its
      blockade antibodies for 14 days. Myeloid DCs can be generated from peripheral
      blood monocytes, and both IL-4 and GM-CSF can provide sufficient stimulus for
      their differentiation. The formation of MGC can be induced in the presence of TNF
      alpha. This reaction was prohibited by the presence of the TNF-neutralizing
      antibody but not by the presence of anti-TNF receptor II antibody. The activation
      of Rho and focal adhesion kinases induced by TNF-alpha stimulation might be
      linked to cell assembling and the formation of Langhans-type MGCs. MGCs can
      produce only small amounts of superoxide anions compared to isolated macrophages
      such as myeloid DCs.

PMID- 21851386
TI  - Melatonin reduces the expression of alpha-synuclein in the dopamine containing
      neuronal regions of amphetamine-treated postnatal rats.
AB  - Alpha-synuclein (alpha-syn) is a neuronal protein that is involved in various
      degenerative disorders such as Parkinson's disease. It is found in the
      presynaptic terminals and perinuclear zones of many brain regions. Amphetamine
      (AMPH), a psychostimulant drug abused progressively more commonly in recent
      years, has been known to induce neurotoxicity in the central dopaminergic
      pathway, which is associated with increased oxidative stress. Recently, AMPH has
      been shown to significantly increase the level of alpha-syn in dopaminergic
      neuroblastoma cell cultures. Melatonin is recognized as an antioxidant for the
      nervous system. This study tested whether melatonin can attenuate the effect of
      AMPH on the expression of alpha-syn in the dopaminergic pathway of the neonatal
      rat. Four-day old postnatal rats (P4) were injected subcutaneously with either
      AMPH (increasing dose, 5-10 mg/kg daily) alone or AMPH with melatonin (2 mg/kg)
      daily at 10:00 AM for 7 consecutive days. As determined using Western blot, the
      level of alpha-syn was significantly increased in the substantia nigra, dorsal
      striatum, nucleus accumbens, and prefrontal cortex of the AMPH-treated group,
      while melatonin treatment either prior to AMPH or alone decreased the
      accumulation of the protein to 77%, 96%, 78%, and 77% of the control value,
      respectively. Furthermore, an immunofluorescent study showed that the alpha-syn
      immunoreactivity increased noticeably in the nuclei of cell bodies and nerve
      terminals of the AMPH-treated group. Again, melatonin lowered this
      immunoreactivity. These results indicate that melatonin has a direct or indirect
      effect in reducing the expression of alpha-syn in the postnatal rat. The exact
      mechanism of this mitigation should be further investigated.

PMID- 21851387
TI  - Renal endpoints in renal and cardiovascular randomized clinical trials: time for
      a consensus?
AB  - Several recent major randomized clinical trials (RCTs) using renal outcomes
      resulted in conflicting results. We searched MEDLINE via PubMed with the search
      request '(dialysis OR end-stage renal disease) and creatinine' in six major
      general journals and two leading journals of nephrology; 123 articles were found;
      17/123 were relevant RCTs. Some disagreement among surrogate endpoints in 11/15
      articles (missing data in two RCTs) and between surrogate and hard renal
      endpoints in 10/13; the intervention effects were in the opposite direction in
      4/15, mostly in patients with cardiovascular disease, but discrepancies and
      conflicting results were also found among renal trials. Among our selected RCTs,
      14/17 used composite endpoints: vital and renal endpoints were mixed in 11/14
      trials, the components of the composite endpoints were of similar importance in
      0/14 trials and of similar frequency in 1/11 trials, the intervention was likely
      to have a similar effect on the components in 4/14 trials, and the relative risk
      reduction was similar for the different components in 2/10 trials. None of the
      trials fulfiled all conditions of validation. Based on this analysis, we believe
      that the current use of renal endpoints in RCTs must be reviewed and their
      conditions of validation defined.

PMID- 21851388
TI  - Rivaroxaban for the prevention and treatment of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common and often life-threatening
      cardiovascular disorder. Patients undergoing total hip replacement or total knee
      replacement surgery are at increased risk of VTE. In this setting, clinical
      practice guidelines recommend the use of low molecular weight heparins, vitamin K
      antagonists or fondaparinux for the prevention of VTE. However, the use of these
      anticoagulants is beset by practical difficulties that reduce compliance to
      therapy and adherence to recommended guidelines. New oral anticoagulants (OACs)
      that are administered in fixed doses without the need for monitoring are now
      being introduced to clinical practice. Rivaroxaban, dabigatran and apixaban are
      either approved or in advanced stages of clinical development for the prevention
      and/or treatment of VTE. This article provides an overview of the phase III
      clinical development programmes for these novel OACs, with special focus on
      rivaroxaban. With encouraging data already emerging, the promise of a simplified
      single-drug approach for VTE treatment is on the horizon.

PMID- 21851389
TI  - Common clinical quandaries encountered in dialysis and ESRD: questions answered.

PMID- 21851390
TI  - Should screening for acquired cystic disease and renal malignancy be undertaken
      in dialysis patients?

PMID- 21851391
TI  - Should high-dose oral diuretics be used to increase urine output in patients on
      chronic peritoneal and hemodialysis?

PMID- 21851392
TI  - What is the role of renal transplantation in a patient with nephrogenic systemic
      fibrosis?

PMID- 21851393
TI  - What are the current recommendations for antibiotic prophylaxis for dental work
      and colonoscopies in HD patients?

PMID- 21851394
TI  - What are the options for anticoagulation needs in dialysis for patients with
      heparin-induced thrombocytopenia?

PMID- 21851395
TI  - Does the risk exceed the benefit for anticoagulation in end-stage renal disease
      patients with nonrheumatic atrial fibrillation?

PMID- 21851396
TI  - Should arteriovenous access flow undergo regular surveillance?

PMID- 21851397
TI  - Is a forearm loop AVG preferable to an upper arm AVF in an octogenarian
      initiating dialysis?

PMID- 21851398
TI  - Can an arteriovenous dialysis access be salvaged when a clinically significant
      steal develops?

PMID- 21851399
TI  - How should clinicians interpret cardiac troponin values in patients with ESRD?

PMID- 21851400
TI  - Are levels of brain natriuretic peptides useful to determine volume status in
      dialysis patients?

PMID- 21851401
TI  - Why are some dialysis patients chronically hypotensive in the absence of heart
      disease and volume depletion?

PMID- 21851402
TI  - How should the predialysis plasma sodium level be interpreted in hemodialysis
      patients?

PMID- 21851403
TI  - What is the best chronic dialysis modality for ESRD patients with end-stage liver
      disease?

PMID- 21851404
TI  - Is there any role for sodium modeling in the prevention of intradialytic
      hypotension in patients with large interdialytic fluid gains?

PMID- 21851405
TI  - Should activated vitamin D be used in patients with end-stage renal disease and
      low levels of parathyroid hormone?

PMID- 21851406
TI  - Should teriparatide ever be used for adynamic bone disease?

PMID- 21851407
TI  - What is the role of using sodium thiosulfate or bisphosphonates in the treatment
      for calciphylaxis?

PMID- 21851408
TI  - What is the risk of hepatitis C spread within dialysis units and how can we
      curtail it?

PMID- 21851409
TI  - Is the Tenckhoff catheter still the first choice for use with peritoneal
      dialysis?

PMID- 21851410
TI  - Should cefazolin or vancomycin be used for initial empiric coverage for
      Staphylococcus aureus in peritoneal dialysis associated peritonitis?

PMID- 21851411
TI  - Early cannulation grafts in straight axillo-axillary angioaccesses avoid central
      catheter insertions.
AB  - The need for early cannulation grafts exists to prevent use of central venous
      catheters. We report our experience in patients who had a straight axillo
      axillary angioaccess. All patients who have undergone an early cannulation axillo
      axillary angioaccess between 2008 and 2010 were reviewed. Fifteen patients had 16
      procedures. Of these, eight were women and their mean age was 56. All patients
      had exhausted access options bilaterally. All had previous catheter insertions
      with either sepsis or jugular veins thrombosis. They all had an axillary artery
      to axillary vein angioaccess using an early cannulation graft. Flixene((r))
      (Atrium Medical, Hudson, NH, USA) was used in 10 cases, whereas Rapidax((r))
      (Vascutek Ltd., Renfrewshire, UK) in 6. In 12 cases, grafts were cannulated after
      12 hours, in 4 after 24 hours (12 hours-8 days, mean 1.8 days). For Flixene((r))
      , mean delay to cannulation was 1.1 days, whereas 2.71 for Rapidax((r)) (p <
      0.05). Primary patency rates were 92.9% and 65.7% at 6 weeks and 1 year,
      respectively. Secondary patency rates were 92.9% and 83.5%. There was no
      significant difference in patency rates between grafts. Early cannulation grafts
      in a complex position are safe and efficient considering their patency and
      complication rates. It avoids using central venous catheters.

PMID- 21851413
TI  - Universal vaccines: shifting to one for many or shooting too high too soon!
AB  - Switching from conventional strain-specific vaccines to multi-strain or multi
      species universal vaccines is both justified and scientifically merited. Long
      term cross-protective universal vaccines eliminate the need for repetitive short
      term vaccination campaigns and short-notice vaccine redesign during impending
      epidemics. They also have the potential to be cost-effective, convenient, and
      amenable to stockpiling. Ongoing advances in genomics and reverse vaccinology
      along with the perceived ability of vaccines, if properly formulated, to induce
      cross-protective adaptive immunity and long-term T cell memory are at the heart
      of this trend. Consequently, the search for universal vaccines against influenza,
      HIV, and many other viral, bacterial, and fungal pathogens has intensified in
      recent years. Currently, several universal influenza vaccines are at different
      phases of clinical evaluation. That said, vaccine-related differential
      effectiveness, escape mutants, pathogen strain replacement, limited scope of
      cross-protective immunity, and diminished potential to reach optimal herd
      immunity thresholds present serious challenges to the concept and applicability
      of universal vaccines. Herein, the case for and the case against universal
      vaccines are investigated to realistically appreciate their prospects of success.

PMID- 21851414
TI  - Prognostic significance of micropapillary pattern in lung adenocarcinoma and
      expression of apoptosis-related markers: caspase-3, bcl-2, and p53.
AB  - We evaluated the clinicopathological characteristics and prognostic significance
      of lung adenocarcinoma with micropapillary pattern (MPP) and analyzed the
      expression of apoptosis-related markers: caspase-3, bcl-2, and p53. A series of
      166 lung adenocarcinoma that had been surgically resected between 2004 and 2009
      were reviewed. Histopathologic patterns, presence of tumor necrosis, mitosis,
      lymphovascular and perineural invasion, the status of pleura, and tumor
      differentiation were examined. Of the 166 patients; 71 were stage I, 35 stage II,
      51 stage III, and nine stage IV. Histologically they were divided into two
      groups: MPP-positive (n = 55) and MPP-negative (n = 111). The following items
      were significantly more frequent in the MPP positive group: female gender (p =
      0.03), lymph node metastasis (p = 0.031), and pleural invasion (p = 0.045). Age,
      smoking status, tumor stage, lymphatic invasion, perineural invasion, mitotic
      count, and survival rates had no statistically significant difference between
      groups (p > 0.05). In MPP positive tumors, visceral pleural invasion was
      identified significantly more frequent than in MPP negative tumors, at stage I.
      Tumors with MPP showed elevated expressions of caspase-3 (94.5%), p53 (60%), and
      bcl-2 (54.5%). In MPP positive group, the expression of these three markers had
      no statistically significant impact on survival. In whole population, bcl-2
      expression was correlated with a better outcome. We conclude that MPP is
      associated with poor prognostic factors both in early and late stages in lung
      adenocarcinoma. Bcl-2 provides prognostic information independent from the MPP.

PMID- 21851415
TI  - Epidemiological studies of Beijing strains of Mycobacterium tuberculosis from
      Taipei and other Asian cities based on MIRU profiles.
AB  - The aim of the present study was to investigate the distribution of the Beijing
      strains of Mycobacterium tuberculosis (MTB) in Taipei and other Asian cities. A
      total of 323 MTB isolates were analyzed by spacer oligonucleotide typing
      (spoligotyping) and mycobacterial interspersed repetitive unit (MIRU) typing. The
      largest cluster of the TB isolates from Taipei was type MT11 (MIRU type 2233-2517
      3533). A comparison of the MIRU type data for the Beijing strains from Taipei and
      previously published MIRU type data for the Beijing strains from Asian cities
      with major population of Chinese was analyzed. The six major Beijing MIRU types
      (MT01, MT02, MT08, MT11, MT21, and MT44) were found to be common in four Asian
      cities including Taipei, Singapore, Hong Kong, and Wuhan. Results of this study
      indicate that there is geographical difference in the distribution of different
      Beijing strains of MTB.

PMID- 21851416
TI  - Graft morphology correlates with fibroblast activity in cardiac allograft
      rejection.
AB  - Several extracellular matrix substances, such as hyaluronan and fibronectin, may
      affect graft viability by their involvement in cell adhesion and in migration.
      These substances are produced locally in the tissue by fibroblasts. The aim of
      this study was to investigate the activation state of intragraft fibroblasts
      under various immunosuppressive treatments and to correlate these with
      morphological parameters. Syngeneic (n = 5) and allogeneic rat (n = 5-6/group)
      heterotopic heart transplantations were performed. Allogeneically transplanted
      animals were immunosuppressed with cyclosporine, mycophenolate mofetil or
      prednisolone. After 10 days, the transplanted hearts were removed for subsequent
      isolation of intragraft fibroblasts and for evaluation of graft morphology. The
      hyaluronan synthesis of graft fibroblasts correlated with the cellular
      infiltration (p < 0.05) and the interstitial oedema (p < 0.05) of the cardiac
      grafts. In general, proliferation rate and hyaluronan production were of the same
      magnitude in fibroblasts from allogeneic hearts under immunosuppression with
      cyclosporine, mycophenolate mofetil or prednisolone as in fibroblasts from
      syngeneic grafts. A pool of fibroblasts isolated from cardiac grafts of non
      immunosuppressed, allogeneically transplanted rats (n = 4) showed considerably
      higher levels. We concluded that fibroblast activity correlates to the viability
      of the tissue rather than to the specific drug used for immunosuppression.

PMID- 21851417
TI  - Placental trophoblasts shifted Th1/Th2 balance toward Th2 and inhibited Th17
      immunity at fetomaternal interface.
AB  - The aims were to clarify the effect of placental trophoblasts on T lymphocytes by
      assessing production of cytokines and expression of transcription factors
      regulating Th1, Th2, and Th17 immunity in T lymphocytes. Placental trophoblasts
      were isolated and conditioned medium was made after trophoblast cultivation for
      72 h. T lymphocytes were cultured in presence or absence of conditioned medium.
      ELISA was used to detect concentration of IL-2, TNF-alpha, IFN-gamma, IL-4, IL
      10, and IL-17 in supernatants of T cell and real-time PCR was used to detect the
      status of Th1 (T-bet, STAT-4), Th2 (GATA-3, STAT-6), and Th17 (RORC) immunity in
      T lymphocyte. We found that the level of IL-2, IFN-gamma, TNF-alpha, and IL-17
      was significantly decreased when T lymphocytes were cultured in conditioned
      medium compared with control, while IL-10 and IL-4 level were not significantly
      changed. The presence of conditioned medium significantly decreased the ratio of
      Th1/Th2. The expression of GATA-3 and STAT-6 were significantly increased and
      STAT-4 was reduced when T lymphocyte was cultured in conditioned medium, while
      the expression of T-bet and RORC was not significantly different. We concluded
      that placental trophoblast-induced shift of Th1/Th2 balance toward Th2 and
      inhibition of Th17 might be among the mechanisms involved in maternal tolerance
      to fetus.

PMID- 21851418
TI  - Variable beta-glucans production by different states of Eurotium amstelodami
      explains differences in inflammatory responses in airway cells.
AB  - Eurotium amstelodami, a mold frequently identified in housing and farm air
      samples, is a suspected cause of respiratory diseases such as allergic
      alveolitis, atopic asthma, and organic dust toxic syndrome. This fungus is
      present in the air in three different states (ascospores, conidia, and hyphae).
      The aim of this study was to test in vitro the differential inflammatory response
      of airway cells exposed to 1,3 betaglucanase-treated protein extract (BGPE), from
      E. amstelodami ascospores, conidia, and hyphae. Confluent cells from the A549
      cell line were inoculated with calibrated BGPE issued from the three fungal
      forms. The levels of eight cytokines and chemokines involved in inflammatory
      responses were measured after 8 h of exposure. Beta-d-glucan (BDG) was quantified
      in total fungal extract as well as in the BGPE from the three fungal states.
      Hyphal BGPE were the only ones to induce a marked inflammatory response and they
      contain higher quantities of BDG. The present study adds to the growing body of
      evidence that beta-glucan from fungal hyphae play a crucial role in respiratory
      diseases.

PMID- 21851419
TI  - Cardiac myxoma in Iceland: a case series with an estimation of population
      incidence.
AB  - Cardiac myxoma (CM) is the most common primary benign tumor of the heart, but the
      true age-standardized incidence rate (ASR) has remained unknown. We therefore
      used nationwide registries in Iceland to study CM and establish its incidence
      rate. This was a retrospective study involving all patients diagnosed with CM in
      Iceland between 1986 and 2010. Cases were identified through three different
      registries, and hospital charts and histology results reviewed. An ASR was
      estimated based on a world standard population (w). Nine cases of CM (six women)
      were identified with a mean age of 62.8 years (range: 37-85), giving an ASR of
      0.11 (95% CI: 0.05-0.22) per 100,000. The mean tumor size was 4.4 cm (range: 1.5
      8.0) with all the tumors located in the left atrium. Dyspnea (n = 6) and ischemic
      stroke (n = 2) were the most common symptoms. All patients underwent complete
      resection of the tumor and there were no postoperative deaths or CM-related
      deaths at follow-up (mean 85 months). The ASR of CM in Iceland was 0.11 per
      100,000. To our knowledge, this is the first study to determine the incidence of
      CM in an entire population. In Iceland, the presenting symptoms and mode of
      detection of CM are similar to those in other series.

PMID- 21851420
TI  - Association of polycystic ovarian syndrome with human leukocyte antigen
      polymorphism in Korean women.
AB  - Although several studies have demonstrated the genetic contribution to polycystic
      ovarian syndrome (PCOS), the cause of this syndrome remains unclear. The aim of
      this study was to elucidate the relationship between human leukocyte antigen
      (HLA) systems and PCOS in Koreans. We compared the HLA-A, B and DRB1 genotype
      distribution of 52 PCOS patients and 67 healthy Korean women. In addition, we
      investigated the association of HLA with free-testosterone level. HLA-A*11, A*31
      and B*54 showed increased phenotype frequencies (PFs) in PCOS women compared to
      controls (p = 0.032, OR 2.79; p = 0.019, OR 6.05; p = 0.002, OR 6.40). HLA
      DRB1*15 showed negative correlations with the free-testosterone concentration
      both in total subjects and PCOS patients (p = 0.024 and p = 0.008). The results
      of the study suggest mild associations of HLA alleles with pathophysiology of
      PCOS and/or testosterone production in PCOS. Further investigation in a large
      number of subjects, including subdivision and multi-population studies, will need
      to be conducted to prove the consistent or variable association in PCOS.

PMID- 21851421
TI  - The role of Campylobacter jejuni cytolethal distending toxin in gastroenteritis:
      toxin detection, antibody production, and clinical outcome.
AB  - The role of Campylobacter jejuni cytolethal distending toxin (CDT) on clinical
      outcome after gastroenteritis was investigated. Clinical data, blood serum
      samples, and Campylobacter spp. isolated, from each of 30 patients were collected
      over a period of 6 months. The CDT encoding genes, cdtABC, characterized by PCR,
      revealed that all but one of the C. jejuni strains had the wild-type sequence.
      Sequencing of cdtABC from this strain showed two major deletions. From all of the
      strains, CDT titers were determined, and toxin neutralizing antibodies were
      documented using an in vitro assay. Three of the thirty clinical isolates,
      including the one with the mutant cdtABC coding genes, did not have a detectable
      CDT activity. Analyzing the relationship between CDT titer, serum neutralization
      of CDT, and the clinical outcome showed that campylobacteriosis caused by CDT
      negative strains was clinically indistinguishable from that of patients infected
      with an isolate that produced high levels of CDT. These results suggest that CDT
      does not solely determine severity of infection and clinical outcome.

PMID- 21851422
TI  - Involvement of red blood cells in the regulation of leukotriene synthesis in
      polymorphonuclear leucocytes upon interaction with Salmonella Typhimurium.
AB  - Leukotriene (LT) B4 is the primary eicosanoid product of polymorphonuclear
      leucocytes (PMNLs). We studied LT synthesis in PMNLs upon interaction with
      Salmonella enterica serovar Typhimurium. Human PMNLs exposed to Salmonella
      produced LTs; mostly LTB4 and omega-hydroxy-LTB4. Opsonization with normal serum
      increased the capacity of S. Typhimurium to induce LT synthesis in PMNLs.
      Addition of red blood cells (RBCs) alone did not activate LT synthesis in PMNLs
      but did further increase the Salmonella-induced release of LTs. Priming of PMNLs
      with lipopolysaccharide before the addition of bacteria potentiated LT synthesis
      in these cells. The effect was more pronounced in the presence of RBCs. We found
      that RBCs diminished the effect of exogenously added NO donors on LT synthesis in
      PMNLs. We conclude that RBCs mediate the activation of LT synthesis in PMNLs
      exposed to Salmonella bacteria at least in part by regulating the intercellular
      exchange and metabolism of NO.

PMID- 21851423
TI  - Gonorrhoea surveillance, laboratory diagnosis and antimicrobial susceptibility
      testing of Neisseria gonorrhoeae in 11 countries of the eastern part of the WHO
      European region.
AB  - Quality-assured worldwide surveillance of antimicrobial resistance (AMR) in
      Neisseria gonorrhoeae is crucial for public health purposes. In the countries of
      the eastern part of the WHO European region the knowledge regarding gonococcal
      AMR is limited, and antimicrobials of many different types, sources and quality
      are used for gonorrhoea treatment. This study surveyed gonorrhoea incidence,
      laboratory diagnosis and gonococcal AMR testing in 11 independent countries of
      the former Soviet Union. The national gonorrhoea incidences remain mainly high.
      In general, gonococcal culture and AMR testing were rarely performed, poorly
      standardized and rarely quality assured. To establish a gonococcal AMR
      surveillance programme in Eastern Europe, i.e. the geographical area of the
      former Soviet Union, several actions have recently been undertaken by the Eastern
      European Sexual and Reproductive Health (EE SRH) Network and the WHO. The
      information provided herein will be useful in this respect.

PMID- 21851424
TI  - Prevalence and correlation of conventional and lupus-specific risk factors for
      cardiovascular disease in Chinese systemic lupus erythematosus patients.
AB  - BACKGROUND: It has become clear that the morbidity and mortality of patients with
      lupus and cardiovascular disease (CVD) have substantially increased. Therefore,
      we designed a retrospective case-control study to assess the prevalence of
      traditional and lupus-specific risk factors for CVD in Chinese systemic lupus
      erythematosus (SLE) patients. OBJECTIVE: To identify the prevalence and
      correlation of conventional and lupus-specific risk factors for CVD in Chinese
      SLE patients. METHODS: One hundred and thirty-nine patients with SLE were
      enrolled in the study. They were compared with 139 age and gender-matched
      controls, who had no history of SLE or CVD. Among 139 SLE patients, there were 38
      with CVD. We compared them with 38 SLE patients without CVD, matching for disease
      duration and age. Data regarding classic and lupus-specific risk factors were
      assessed between the two groups. RESULTS: Hypertension, serum creatinine and
      diabetes mellitus were more prevalent among SLE than the controls (P < 0.05). The
      patients with SLE were more likely to have elevated total, low-density
      lipoprotein cholesterol and triglyceride levels than the controls (P < 0.001).
      However, high-density lipoprotein levels in SLE patients were lower than that in
      controls (P = 0.019). After being compared with SLE patients without CVD, the
      patients with both SLE and CVD were more likely to have elevated serum
      creatinine, proteinuria, the presence of anti-Sm antibody and decreased
      complement 4 (C4) levels (P < 0.05). Moreover, the patients with both diseases
      were less likely to be treated with hydroxychloroquine (P < 0.05). In
      multivariable analysis, elevated serum creatinine, proteinuria, decreased C4
      levels, the presence of anti-Sm antibody and the lack of using hydroxychloroquine
      were independent risk factors for CVD (P < 0.05). CONCLUSIONS: We are able to
      identify some conventional and lupus-specific risk factors for CVD in Chinese SLE
      patients.

PMID- 21851425
TI  - Acral lesions of vitiligo: why are they resistant to photochemotherapy?
AB  - BACKGROUND: Acral lesions of vitiligo are usually resistant to conventional lines
      of treatment as well as surgical interventions. OBJECTIVE: To clarify causes
      underlying resistance of acral lesions to pigmentation in vitiligo by studying
      some of the factors associated with mechanisms of repigmentation following
      photochemotherapy. METHODS: The study included twenty patients with active
      vitiligo. Skin biopsies were taken from lesional and perilesional skin of areas
      expected to respond (trunk and proximal limb) and skin of acral areas, before and
      after PUVA therapy. Sections were stained with H and E, Melan-A, MHCII, CD1a, SCF
      and c-kit protein. RESULTS: Before treatment acral areas showed significantly
      lower hair follicle density, melanocyte density, Langerhans cell (LC) density,
      epidermal MHCII expression, lesional SCF expression and perilesional c-kit
      expression. Following treatment with PUVA in both non-responsive acral and
      repigmenting non-acral lesions identical immunohistochemical changes in the form
      of significant decrease in LC density, epidermal MHC-II and SCF expression were
      observed. CONCLUSION: The surprisingly similar histochemical changes in response
      to PUVA in acral and non-acral lesions did not manifest with clinical
      repigmentation except in non-acral ones. Factors such as inherent lower
      melanocyte density, lower melanocyte stem cell reservoirs and/or lower baseline
      epidermal stem cell factor may be considered as possible play makers in this
      respect.

PMID- 21851426
TI  - A suitable duplex PCR for ovine embryo sex and genotype of PrnP gene
      determination for MOET-based selection programmes.
AB  - The objective of this study was to test the suitability of a duplex PCR assay for
      sex and scrapie resistance genotype determination in fresh embryos. Duplex PCR
      amplified a repetitive and specific fragment of Y chromosome, used for sex
      diagnosis, and a PrnP fragment. PrnP codons 134 and 156, and codon 171 were
      genotyped by restriction fragment length polymorphisms and allele-specific PCR,
      respectively, after re-amplification of PrnP fragment. The specificity of the
      method was first assessed by testing 359 blood samples from Rasa Aragonesa sheep
      breed (161 males and 198 females). No amplification failures and total agreement
      between genotypic and phenotypic sex were found. In the same way, PrnP genotype
      determination by duplex PCR assay was in agreement with the PrnP animal's
      genotype established by sequencing. Finally, 73 samples of 1-10 cells from
      compact morulae were aspirated through the zona pellucida and genotyped for sex
      and PrnP. The efficiency was 96% when three or more cells were sampled. These
      results confirm that the duplex PCR assay reported in this work can be used for
      rapid sex determination in ovine embryos, with a high efficiency and accuracy
      (96%) when three or more cells are sampled, allowing sexed fresh embryos of known
      PrnP genotype to be transferred in multiple ovulation and embryo transfer
      programmes.

PMID- 21851427
TI  - Prolactin induces a hyperpolarising current in rat paraventricular oxytocinergic
      neurones.
AB  - Prolactin and oxytocin are important reproductive hormones implicated in several
      common adaptive functions during pregnancy, pseudopregnancy and lactation.
      Recently, extracellular recordings of supraoptic neurones have shown that
      prolactin may modulate the electrical activity of oxytocinergic neurones.
      However, no study has been conducted aiming to establish whether prolactin
      directly influences this activity in oxytocinergic paraventricular neurones. In
      the present study, we addressed this question by studying the effects of
      prolactin on the electrical activity and voltage-current relationship of
      identified paraventricular neurones in rat brain slices. Whole-cell recordings
      were obtained and neurones were classified on the basis of their morphological
      and electrophysiological fingerprint (i.e. magnocellular or parvicellular) and
      neuropeptide phenotype (i.e. oxytocinergic or non-oxytocinergic). We report that
      prolactin elicited a hyperpolarising current in 37% of the neurones in this
      nucleus, of which the majority (67%) were identified as putative magnocellular
      oxytocin neurones and the reminder (33%) were regarded as oxytocin-negative,
      parvicellular neuroendocrine neurones. Our results suggest that, in addition to
      the well-established negative feedback loop between prolactin-secreting
      lactotrophs and dopaminergic neurones in the arcuate nucleus, an inhibitory
      feedback loop also exists between lactotrophs and oxytocinergic paraventricular
      neurones.

PMID- 21851429
TI  - Cryoprecipitate transfusion: assessing appropriateness and dosing in trauma.
AB  - BACKGROUND: Originally developed for patients with congenital factor VIII
      deficiency, cryoprecipitate is currently largely used for acquired
      hypofibrinogenemia in the context of bleeding. However, scant evidence supports
      this indication and cryoprecipitate is commonly used outside guidelines. In
      trauma, the appropriate cryoprecipitate dose and its impact on plasma fibrinogen
      levels are unclear. OBJECTIVES: The aims were to evaluate (i) the appropriateness
      of cryoprecipitate transfusion in trauma and (ii) the plasma fibrinogen response
      to cryoprecipitate transfusion during massive transfusion in trauma. METHODS:
      Retrospective review (January 1998-June 2008) of indications, dose and plasma
      fibrinogen response to cryoprecipitate transfusion at a large teaching hospital.
      A fibrinogen of <1.0 g L(-1) within 2 and 6 h of transfusion was used for
      evaluating appropriateness. RESULTS: Ten thousand five hundred and forty
      cryoprecipitate units were transfused in 1004 patients. Thirty-seven percent and
      31% were used in cardiac surgery and trauma, respectively. In 394 events in
      trauma, 238 (60%) and 259 (66%) were considered appropriate using the 2- and 6-h
      cut-off criteria, respectively. In patients who did not receive plasma components
      2 h prior to cryoprecipitate, a dose of 8.7 (+/- 1.7) units caused a mean
      increase in fibrinogen levels of 0.55 (+/- 0.24) g L(-1), or 0.06 g L(-1) per
      unit. CONCLUSIONS: In our hospital, where transfusion guidelines are overseen by
      transfusion medicine specialists and technologists, and policies for rapid blood
      component and laboratory turnaround times exist, it is possible to achieve high
      rates of appropriateness for cryoprecipitate transfusion in trauma. The current
      recommended dose causes a modest increase in fibrinogen levels (0.55 g L(-1) ).

PMID- 21851430
TI  - Combined transcription factor profiling, microarray analysis and metabolite
      profiling reveals the transcriptional control of metabolic shifts occurring
      during tomato fruit development.
AB  - Maturation of fleshy fruits such as tomato (Solanum lycopersicum) is subject to
      tight genetic control. Here we describe the development of a quantitative real
      time PCR platform that allows accurate quantification of the expression level of
      approximately 1000 tomato transcription factors. In addition to utilizing this
      novel approach, we performed cDNA microarray analysis and metabolite profiling of
      primary and secondary metabolites using GC-MS and LC-MS, respectively. We applied
      these platforms to pericarp material harvested throughout fruit development,
      studying both wild-type Solanum lycopersicum cv. Ailsa Craig and the hp1 mutant.
      This mutant is functionally deficient in the tomato homologue of the negative
      regulator of the light signal transduction gene DDB1 from Arabidopsis, and is
      furthermore characterized by dramatically increased pigment and phenolic
      contents. We choose this particular mutant as it had previously been shown to
      have dramatic alterations in the content of several important fruit metabolites
      but relatively little impact on other ripening phenotypes. The combined dataset
      was mined in order to identify metabolites that were under the control of these
      transcription factors, and, where possible, the respective transcriptional
      regulation underlying this control. The results are discussed in terms of both
      programmed fruit ripening and development and the transcriptional and metabolic
      shifts that occur in parallel during these processes.

PMID- 21851428
TI  - Roles for oestrogen receptor beta in adult brain function.
AB  - Oestradiol exerts a profound influence upon multiple brain circuits. For the most
      part, these effects are mediated by oestrogen receptor (ER)alpha. We review here
      the roles of ERbeta, the other ER isoform, in mediating rodent oestradiol
      regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin
      secretion, and adult neurogenesis. Evidence exists for: (i) ERbeta located in the
      paraventricular nucleus underpinning the suppressive influence of oestradiol on
      the stress axis and anxiety-like behaviour; (ii) ERbeta expressed in
      gonadotrophin-releasing hormone neurones contributing to oestrogen negative
      feedback control of gonadotrophin secretion; (iii) ERbeta controlling the offset
      of lordosis behaviour; (iv) ERbeta suppressing aggressive behaviour in males; (v)
      ERbeta modulating responses to social stimuli; and (vi) ERbeta in controlling
      adult neurogenesis. This review highlights two major themes; first, ERbeta and
      ERalpha are usually tightly inter-related in the oestradiol-dependent control of
      a particular brain function. For example, even though oestradiol feedback to
      control reproduction occurs principally through ERalpha-dependent mechanisms,
      modulatory roles for ERbeta also exist. Second, the roles of ERalpha and ERbeta
      within a particular neural network may be synergistic or antagonistic. Examples
      of the latter include the role of ERalpha to enhance, and ERbeta to suppress,
      anxiety-like and aggressive behaviours. Splice variants such as ERbeta2, acting
      as dominant negative receptors, are of further particular interest because their
      expression levels may reflect preceeding oestradiol exposure of relevance to
      oestradiol replacement therapy. Together, this review highlights the predominant
      modulatory, but nonetheless important, roles of ERbeta in mediating the many
      effects of oestradiol upon adult brain function.

PMID- 21851432
TI  - Sequence divergence and loss-of-function phenotypes of S locus F-box brothers
      genes are consistent with non-self recognition by multiple pollen determinants in
      self-incompatibility of Japanese pear (Pyrus pyrifolia).
AB  - The S-RNase-based gametophytic self-incompatibility (SI) of Rosaceae, Solanaceae,
      and Plantaginaceae is controlled by at least two tightly linked genes located at
      the complex S locus; the highly polymorphic S-RNase for pistil specificity and
      the F-box gene (SFB/SLF) for pollen. Self-incompatibility in Prunus (Rosaceae) is
      considered to represent a 'self recognition by a single factor' system, because
      loss-of-function of SFB is associated with self-compatibility, and allelic
      divergence of SFB is high and comparable to that of S-RNase. In contrast, Petunia
      (Solanaceae) exhibits 'non-self recognition by multiple factors'. However, the
      distribution of 'self recognition' and 'non-self recognition' SI systems in
      different taxa is not clear. In addition, in 'non-self recognition' systems, a
      loss-of-function phenotype of pollen S is unknown. Here we analyze the divergence
      of SFBB genes, the multiple pollen S candidates, of a rosaceous plant Japanese
      pear (Pyrus pyrifolia) and show that intrahaplotypic divergence is high and
      comparable to the allelic diversity of S-RNase while interhaplotypic divergence
      is very low. Next, we analyzed loss-of-function of the SFBB1 type gene. Genetic
      analysis showed that pollen with the mutant haplotype S(4sm)  lacking SFBB1-S(4) 
      is rejected by pistils with an otherwise compatible S(1)  while it is accepted by
      other non-self pistils. We found that the S(5)  haplotype encodes a truncated
      SFBB1 protein, even though S(5)  pollen is accepted normally by pistils with S(1)
      and other non-self haplotypes. These findings suggest that Japanese pear has a
      'non-self recognition by multiple factors' SI system, although it is a species of
      Rosaceae to which Prunus also belongs.

PMID- 21851433
TI  - Satisfaction and quality of life: a survey-based assessment in patients with a
      totally implantable venous port system.
AB  - The purpose was to assess the satisfaction and quality of life in patients with a
      totally implantable central venous port system using a questionnaire-based
      survey. A self-designed questionnaire to assess patient satisfaction and the
      impact of the port on daily life was dispatched 180 days after implantation. The
      questionnaire was combined with the commonly used short form (SF)-12 Health
      Survey quality of life questionnaire. Of the 98 patients who received a port
      system, 75 were contacted, and 42 (56%) returned the questionnaire. Most of the
      responding patients reported high overall satisfaction. The impact of the system
      on daily life was widely perceived not to be negative. The physical component
      summary (PCS) and the mental component summary (MCS) scores from the SF-12 were
      35.5 and 45.23 respectively (general German population: PCS = 49.6, MCS = 52.3).
      The multiple stepwise regression showed that the cosmetic result was a predictor
      of overall satisfaction; the cosmetic result and a painful port together were
      predictors of the MCS. Overall, it was found that the cosmetic result of the
      implantation procedure was a predictor of satisfaction and quality of life and
      should thus not be underestimated.

PMID- 21851431
TI  - Comparative deep transcriptional profiling of four developing oilseeds.
AB  - Transcriptome analysis based on deep expressed sequence tag (EST) sequencing
      allows quantitative comparisons of gene expression across multiple species. Using
      pyrosequencing, we generated over 7 million ESTs from four stages of developing
      seeds of Ricinus communis, Brassica napus, Euonymus alatus and Tropaeolum majus,
      which differ in their storage tissue for oil, their ability to photosynthesize
      and in the structure and content of their triacylglycerols (TAG). The larger
      number of ESTs in these 16 datasets provided reliable estimates of the expression
      of acyltransferases and other enzymes expressed at low levels. Analysis of EST
      levels from these oilseeds revealed both conserved and distinct species-specific
      expression patterns for genes involved in the synthesis of glycerolipids and
      their precursors. Independent of the species and tissue type, ESTs for core fatty
      acid synthesis enzymes maintained a conserved stoichiometry and a strong
      correlation in temporal profiles throughout seed development. However, ESTs
      associated with non-plastid enzymes of oil biosynthesis displayed dissimilar
      temporal patterns indicative of different regulation. The EST levels for several
      genes potentially involved in accumulation of unusual TAG structures were
      distinct. Comparison of expression of members from multi-gene families allowed
      the identification of specific isoforms with conserved function in oil
      biosynthesis. In all four oilseeds, ESTs for Rubisco were present, suggesting its
      possible role in carbon metabolism, irrespective of light availability. Together,
      these data provide a resource for use in comparative and functional genomics of
      diverse oilseeds. Expression data for more than 350 genes encoding enzymes and
      proteins involved in lipid metabolism are available at the 'ARALIP' website
      (http://aralip.plantbiology.msu.edu/).

PMID- 21851434
TI  - Literature review: using pictographs in discharge instructions for older adults
      with low-literacy skills.
AB  - AIMS: To evaluate current visual aids used in health education; to explore
      evidence regarding the use of pictographs (simple line drawings showing explicit
      health care actions); and to provide suggestions for uses of pictographs in
      discharge instructions for older adults with low-literacy skills. BACKGROUND:
      Discharge instructions consist of recommended homecare actions. However, these
      healthcare actions are provided in text-based discharge instructions, which are
      often difficult for patients with low-literacy skills to follow precisely at
      home. Various forms of visual aids are currently used to improve health
      education; however, the appropriateness of these visual aids for educating
      discharge instructions for older adults with low-literacy skills is unknown.
      DESIGN: A narrative literature review. METHODS: Eligible articles were identified
      via electronic searches of databases. In total, 44 articles were reviewed and
      analysed. RESULTS: Among various visual aids, pictographs using simple line
      drawings combined with simplified text are the most efficient and effective tool
      to improve discharge education. Indeed, pictographs are well suited to show a
      step-by-step procedure of complex and lengthy discharge instructions consisting
      of multiple actions, thus making an entire action sequence easier to learn.
      CONCLUSION: By using pictographs with simplified text, healthcare educators can
      improve discharge instructions for low-literate older adults. Further research is
      needed to develop pictographs representing explicit healthcare actions themselves
      rather than concepts associated with healthcare actions; and to examine the
      effects of pictographs on adherence and health outcomes. RELEVANCE TO CLINICAL
      PRACTICE: Healthcare education materials using pictographs provide effective
      strategies in improving discharge education for low-literate older adults in
      acute healthcare settings where nurses have primary responsibility as a first
      line of healthcare providers. It can also serve as an efficient tool to improve
      health education for immigrants speaking English as a second language.

PMID- 21851435
TI  - A national survey of GP and nurse attitudes and beliefs towards depression after
      myocardial infarction.
AB  - AIM: To investigate primary care practitioner's attitudes to depression after
      myocardial infarction. BACKGROUND: Depression after myocardial infarction affects
      almost half of all patients and has a considerable negative effect on recovery.
      Despite the increased prevalence of depression in this population, it is often
      not recognised or treated. DESIGN: Survey. METHOD: A total of 813 (106 general
      practitioners and 707 nurses) practitioners responded. Our questionnaire
      developed for this project by the authors in collaboration with a group of ten
      cardiovascular nurse specialists contained 27 items that were summated into five
      subscales. RESULTS: Primary care practitioners underestimated the prevalence of
      depression in the post-myocardial infarction population. General acknowledgement
      of the negative impact that depression can have was reported by the majority of
      participants. Diagnosing depression was perceived as complex by both groups but
      significantly more so by nurses. General practitioners were significantly more
      positive about their understanding of the signs and symptoms of depression and in
      using depression-screening tools. We observed that training seems to have a
      significant effect on reported practice. Practitioners who reported that they had
      recent training in the management of depression were significantly more accurate
      in their estimate of how common depression was in this population. CONCLUSION:
      Depression may be underdiagnosed in this population because primary care
      practitioners, especially nurses, are not aware of how common the disorder is and
      lack competence in diagnosis. There is merit in developing and testing a brief
      training intervention to ensure competence in depression screening and treatment
      in post-myocardial infarction patients. RELEVANCE TO CLINICAL PRACTICE:
      Diagnosing depression in post-myocardial infarction patients is perceived by
      nurses as complex but training in the management of depression is seen as helping
      practice.

PMID- 21851436
TI  - Refugial isolation and divergence in the Narrowheaded Gartersnake species complex
      (Thamnophis rufipunctatus) as revealed by multilocus DNA sequence data.
AB  - Glacial-interglacial cycles of the Pleistocene are hypothesized as one of the
      foremost contributors to biological diversification. This is especially true for
      cold-adapted montane species, where range shifts have had a pronounced effect on
      population-level divergence. Gartersnakes of the Thamnophis rufipunctatus species
      complex are restricted to cold headwater streams in the highlands of the Sierra
      Madre Occidental and southwestern USA. We used coalescent and multilocus
      phylogenetic approaches to test whether genetic diversification of this montane
      restricted species complex is consistent with two prevailing models of range
      fluctuation for species affected by Pleistocene climate changes. Our concatenated
      nuDNA and multilocus species analyses recovered evidence for the persistence of
      multiple lineages that are restricted geographically, despite a mtDNA signature
      consistent with either more recent connectivity (and introgression) or recent
      expansion (and incomplete lineage sorting). Divergence times estimated using a
      relaxed molecular clock and fossil calibrations fall within the Late Pleistocene,
      and zero gene flow scenarios among current geographically isolated lineages could
      not be rejected. These results suggest that increased climate shifts in the Late
      Pleistocene have driven diversification and current range retraction patterns and
      that the differences between markers reflect the stochasticity of gene lineages
      (i.e. ancestral polymorphism) rather than gene flow and introgression. These
      results have important implications for the conservation of T. rufipunctatus
      (sensu novo), which is restricted to two drainage systems in the southwestern US
      and has undergone a recent and dramatic decline.

PMID- 21851437
TI  - Clonality, genetic diversity and support for the diversifying selection
      hypothesis in natural populations of a flower-living yeast.
AB  - Vast amounts of effort have been devoted to investigate patterns of genetic
      diversity and structuring in plants and animals, but similar information is
      scarce for organisms of other kingdoms. The study of the genetic structure of
      natural populations of wild yeasts can provide insights into the ecological and
      genetic correlates of clonality, and into the generality of recent hypotheses
      postulating that microbial populations lack the potential for genetic divergence
      and allopatric speciation. Ninety-one isolates of the flower-living yeast
      Metschnikowia gruessii from southeastern Spain were DNA fingerprinted using
      amplified fragment length polymorphism (AFLP) markers. Genetic diversity and
      structuring was investigated with band-based methods and model- and nonmodel
      based clustering. Linkage disequilibrium tests were used to assess reproduction
      mode. Microsite-dependent, diversifying selection was tested by comparing genetic
      characteristics of isolates from bumble bee vectors and different floral
      microsites. AFLP polymorphism (91%) and genotypic diversity were very high.
      Genetic diversity was spatially structured, as shown by amova (Phi(st)  = 0.155)
      and clustering. The null hypothesis of random mating was rejected, clonality
      seeming the prevailing reproductive mode in the populations studied. Genetic
      diversity of isolates declined from bumble bee mouthparts to floral microsites,
      and frequency of five AFLP markers varied significantly across floral microsites,
      thus supporting the hypothesis of diversifying selection on clonal lineages. Wild
      populations of clonal fungal microbes can exhibit levels of genetic diversity and
      spatial structuring that are not singularly different from those shown by
      sexually reproducing plants or animals. Microsite-dependent, divergent selection
      can maintain high local and regional genetic diversity in microbial populations
      despite extensive clonality.

PMID- 21851438
TI  - Phylogeographic heterogeneity of the brown macroalga Sargassum horneri (Fucaceae)
      in the northwestern Pacific in relation to late Pleistocene glaciation and
      tectonic configurations.
AB  - Pleistocene glacial oscillations and associated tectonic processes are believed
      to have influenced the historical abundances and distribution of organisms in the
      Asia Northwest Pacific (ANP). Accumulating evidence indicates that factors
      shaping tempospatial population dynamics and distribution patterns of marine taxa
      vary with biogeographical latitude, pelagic behaviour and oceanographic regimes.
      To detect what kinds of historical and contemporary factors affected genetic
      connectivity, phylogeographic profiles of littoral macroalga Sargassum horneri in
      the ANP were analysed based on mitochondrial (Cox3) and chloroplast (rbcL) data
      sets. Five distinct clades were recovered. A strong signature of biogeographical
      structure was revealed (Phi(CT) = 0.487, P < 0.0001) derived from remarkable
      differentiation in clade distribution, as clade I is restricted to Chinese
      marginal seas (Yellow-Bohai Sea, East China Sea and South China Sea), whereas
      clades II-V are discontinuously scattered around the main Islands of Japan.
      Furthermore, two secondary contact regions were identified along the south Japan
      Pacific coastline. This significant differentiation between the two basins may
      reflect historical glacial isolation in the northwestern Pacific, which is
      congruent with the estimates of clade divergence and demographic expansion during
      the late Quaternary low sea levels. Analysis of molecular variance and the
      population-pair statistic F(ST) also revealed significant genetic structural
      differences between Chinese marginal seas and the Japanese basin. This
      exceptional phylogeographic architecture in S. horneri, initially shaped by
      historical geographic isolation during the late Pleistocene ice age and physical
      biogeographical barriers, can be complicated by oceanographic regimes (ocean
      surface currents) and relocating behaviour such as oceanic drifting.

PMID- 21851439
TI  - Age effects on spectral electroencephalogram activity prior to dream recall.
AB  - Ageing is associated with marked changes in sleep timing, structure and
      electroencephalographic (EEG) activity. Older people exhibit less slow-wave and
      spindle activity during non-rapid eye movement (NREM) sleep, together with
      attenuated levels of rapid eye movement (REM) sleep as compared to young
      individuals. However, the extent to which these age-related changes in sleep
      impact on dream processing remains largely unknown. Here we investigated NREM and
      REM sleep EEG activity prior to dream recall and no recall in 17 young (20-31
      years) and 15 older volunteers (57-74 years) during a 40 h multiple nap protocol.
      Dream recall was assessed immediately after each nap. During NREM sleep prior to
      dream recall, older participants displayed higher frontal EEG delta activity (1-3
      Hz) and higher centro-parietal sigma activity (12-15 Hz) than the young
      volunteers. Conversely, before no recall, older participants had less frontal
      central delta activity and less sigma activity in frontal, central and parietal
      derivations than the young participants. REM sleep was associated to age-related
      changes, such that older participants had less frontal-central alpha (10-12 Hz)
      and beta (16-19 Hz) activity, irrespective of dream recall and no recall. Our
      data indicate that age-related differences in dream recall seem to be directly
      coupled to specific frequency and topography EEG patterns, particularly during
      NREM sleep. Thus, the spectral correlates of dreaming can help to understand the
      cortical pathways of dreaming.

PMID- 21851440
TI  - Russia and human immunodeficiency virus--beyond crime and punishment.

PMID- 21851441
TI  - Relationship between personality change and the onset and course of alcohol
      dependence in young adulthood.
AB  - AIMS: To examine the reciprocal effects between the onset and course of alcohol
      use disorder (AUD) and normative changes in personality traits of behavioral
      disinhibition and negative emotionality during the transition between adolescence
      and young adulthood. DESIGN: Longitudinal-epidemiological study assessing AUD and
      personality at ages 17 and 24 years. SETTING: Participants were recruited from
      the community and took part in a day-long, in-person assessment. PARTICIPANTS:
      Male (n = 1161) and female (n = 1022) twins participating in the Minnesota Twin
      Family Study. MEASUREMENTS: The effects of onset (adolescent versus young adult)
      and course (persistent versus desistent) of AUD on change in personality traits
      of behavioral disinhibition and negative emotionality from ages 17 to 24 years.
      FINDINGS: Onset and course of AUD moderated personality change from ages 17 to 24
      years. Adolescent onset AUD was associated with greater decreases in behavioral
      disinhibition. Those with an adolescent onset and persistent course failed to
      exhibit normative declines in negative emotionality. Desistence was associated
      with a 'recovery' towards psychological maturity in young adulthood, while
      persistence was associated with continued personality dysfunction. Personality
      traits at age 11 predicted onset and course of AUD, indicating personality
      differences were not due to active substance abuse. CONCLUSIONS: Personality
      differences present prior to initiation of alcohol use increase risk for alcohol
      use disorder, but the course of alcohol use disorder affects the rate of
      personality change during emerging adulthood. Examining the reciprocal effects of
      personality and alcohol use disorder within a developmental context is necessary
      to improve understanding for theory and intervention.

PMID- 21851442
TI  - Effect of prison-based opioid substitution treatment and post-release retention
      in treatment on risk of re-incarceration.
AB  - AIMS: People who use heroin are frequently incarcerated multiple times. Reducing
      re-incarceration of this group is important for reducing both health risks
      associated with incarceration and the costs of correctional administration.
      Opioid substitution treatment (OST) in prisons may help to reduce re
      incarceration, but research findings on this topic have been mixed. In this
      study, we examined the effect of OST in prison and after release on re
      incarceration. DESIGN: Longitudinal cohort study. SETTING, PARTICIPANTS AND
      MEASUREMENTS: Data on OST and incarceration were linked for a cohort of 375 male
      heroin users recruited originally in prisons in New South Wales, Australia. Data
      were linked for the period 1 June 1997-31 December 2006. Re-incarceration was
      examined using recurrent-event survival analysis models. Model 1 examined the
      effect of OST status at release from prison (i.e. in treatment versus out of
      treatment on the day of release) on re-incarceration. Model 2 considered the
      effect of remaining in OST after release on risk of re-incarceration. FINDINGS:
      Ninety per cent of participants were re-incarcerated following their first
      observed release. Pre-incarceration cocaine use was associated with a 13%
      increase in the average risk of re-incarceration. There was no significant
      association between simply being in OST at the time of release and risk of re
      incarceration; however, in the model taking into account post-release retention
      in treatment, the average risk of re-incarceration was reduced by 20% while
      participants were in treatment. CONCLUSIONS: In New South Wales, Australia,
      opioid substitution treatment after release from prison has reduced the average
      risk of re-incarceration by one-fifth.

PMID- 21851443
TI  - Examining the predictive validity of low-risk gambling limits with longitudinal
      data.
AB  - AIMS: To assess the impact of gambling above the low-risk gambling limits
      developed by Currie et al. (2006) on future harm. To identify demographic,
      behavioural, clinical and environmental factors that predict the shift from low-
      to high-risk gambling habits over time. DESIGN: Longitudinal cohort study of
      gambling habits in community-dwelling adults. SETTING: Alberta, Canada.
      PARTICIPANTS: A total of 809 adult gamblers who completed the time 1 and time 2
      assessments separated by a 14-month interval. MEASUREMENTS: Low-risk gambling
      limits were defined as gambling no more than three times per month, spending no
      more than CAN$1000 per year on gambling and spending less than 1% of gross income
      on gambling. Gambling habits, harm from gambling and gambler characteristics were
      assessed by the Canadian Problem Gambling Index. Ancillary measures of substance
      abuse, gambling environment, major depression, impulsivity and personality traits
      assessed the influence of other risk factors on the escalation of gambling
      intensity. FINDINGS: Gamblers classified as low risk at time 1 and shifted into
      high-risk gambling by time 2 were two to three times more likely to experience
      harm compared to gamblers who remained low risk at both assessments. Factors
      associated with the shift from low- to high-risk gambling behaviour from time 1
      to time 2 included male gender, tobacco use, older age, having less education,
      having friends who gamble and playing electronic gaming machines. CONCLUSIONS: An
      increase in the intensity of gambling behaviour is associated with greater
      likelihood of future gambling related harm in adults.

PMID- 21851444
TI  - The association between the incidence of emergency department attendances for
      alcohol problems and assault incidents attended by police in New South Wales,
      Australia, 2003-2008: a time-series analysis.
AB  - AIM: To assess the short-term temporal relationship between emergency department
      (ED) attendances for acute alcohol problems and assaults reported to police.
      DESIGN: Cross-sectional time-series analysis. SETTING: Population of New South
      Wales (NSW), Australia between 2003 and 2008. PARTICIPANTS: All patients who
      attended any of 56 large NSW public hospital EDs and had a recorded diagnosis of
      acute alcohol problems, and all persons involved in assault incidents reported to
      the NSW Police Force. MEASUREMENTS: Weekly count time-series were formed for ED
      attendances, assault incidents and persons of interest in assault incidents.
      Cross-correlation analysis was used to determine any time lag in the relationship
      between the alcohol and the assault series. Poisson regression was used to assess
      the magnitude of the relationship. Splines of week controlled for seasonality.
      FINDINGS: There was no time lag found between the ED and police series. A weekly
      increase of 100 attendances in people aged 15 years and above to EDs for alcohol
      problems was associated with an 11% [95% confidence interval (CI): 7-15%]
      increase in the number of incident assaults attended by police. The relationship
      was similar and statistically significant for domestic and non-domestic assaults
      and urban areas. The association was stronger between ED attendances and persons
      of interest aged 15-24 years (27%, 95% CI: 15-41%), 15-24-year-old males (39%,
      95% CI: 16-66%) and 15-24-year-old females (66%, 95% CI: 20-129%). CONCLUSIONS:
      There is a clear, short-term temporal association between independent population
      level markers of excessive alcohol use and violence.

PMID- 21851445
TI  - Cannabis use and subclinical positive psychotic experiences in early adolescence:
      findings from a Dutch survey.
AB  - AIMS: To investigate the association between early cannabis use and subclinical
      psychotic experiences, distinguishing between five levels of use: never used,
      discontinued use (life-time users who did not use in the preceding year),
      experimental use, regular use and heavy use. DESIGN: Cross-sectional
      observational study. SETTING: Dutch Health Behaviour in School-aged Children
      (HBSC) study, 2005 wave. PARTICIPANTS: A total of 4552 secondary school children
      aged 12-16 years. MEASUREMENTS: Cannabis use, Community Assessment of Psychic
      Experiences (CAPE) positive scale, confounding factors: age, gender, family
      affluence, household composition, social support, alcohol use, cigarette smoking,
      ethnicity and urbanicity. FINDINGS: The association between cannabis use and
      subclinical positive symptoms was confirmed, and remained significant after
      extensive adjustment for potential confounders. Associations were found for all
      user groups, with strongest associations for the discontinued use group (beta =
      0.061, P = 0.000) and for the heavy use group (beta = 0.065, P = 0.000).
      CONCLUSIONS: There is an enduring association between cannabis use at an early
      age and subclinical positive psychotic experiences, even after abstaining from
      cannabis for at least 1 year.

PMID- 21851447
TI  - Can we move beyond burden and burnout to support the health and wellness of
      family caregivers to persons with dementia? Evidence from British Columbia,
      Canada.
AB  - After more than a decade of concerted effort by policy-makers in Canada and
      elsewhere to encourage older adults to age at home, there is recognition that the
      ageing-in-place movement has had unintended negative consequences for family
      members who care for seniors. This paper outlines findings of a qualitative
      descriptive study to investigate the health and wellness and support needs of
      family caregivers to persons with dementia in the Canadian policy environment.
      Focus groups were conducted in 2010 with 23 caregivers and the health
      professionals who support them in three communities in the Southern Interior of
      British Columbia. Thematic analysis guided by the constant comparison technique
      revealed two overarching themes: (1) forgotten: abandoned to care alone and
      indefinitely captures the perceived consequences of caregivers' failed efforts to
      receive recognition and adequate services to support their care-giving and (2)
      unrealistic expectations for caregiver self-care relates to the burden of
      expectations for caregivers to look after themselves. Although understanding
      about the concepts of caregiver burden and burnout is now quite developed, the
      broader sociopolitical context giving rise to these negative consequences for
      caregivers to individuals with dementia has not improved. If anything, the
      Canadian homecare policy environment has placed caregivers in more desperate
      circumstances. A fundamental re-orientation towards caregivers and caregiver
      supports is necessary, beginning with viewing caregivers as a critical health
      human resource in a system that depends on their contributions in order to
      function. This re-orientation can create a space for providing caregivers with
      preventive supports, rather than resorting to costly patient care for caregivers
      who have reached the point of burnout and care recipients who have been
      institutionalised.

PMID- 21851446
TI  - The contributions of physician assistants in primary care systems.
AB  - Shortages of primary care doctors are occurring globally; one means of meeting
      this demand has been the use of physician assistants (PAs). Introduced in the
      United States in the late 1960s to address doctor shortages, the PA movement has
      grown to over 75,000 providers in 2011 and spread to Australia, Canada, Great
      Britain, the Netherlands, Germany, Ghana and South Africa. A purposeful
      literature review was undertaken to assess the contribution of PAs to primary
      care systems. Contemporary studies suggest that PAs can contribute to the
      successful attainment of primary care functions, particularly the provision of
      comprehensive care, accessibility and accountability. Employing PAs seems a
      reasonable strategy for providing primary care for diverse populations.

PMID- 21851448
TI  - New drugs for Alzheimer's disease in Japan.

PMID- 21851449
TI  - Strategies and future attempts to reduce stigmatization and increase awareness of
      mental health problems among young people: a narrative review of educational
      interventions.
AB  - There is a need to reduce stigma and increase awareness in order to prevent
      social exclusion of people with mental illness and to facilitate the use of
      mental health services in young people. The purpose of this review was to examine
      the effects of educational interventions to reduce stigmatization and improve
      awareness of mental health problems among young people. An electronic search
      using MEDLINE, PsycINFO and Academic Search Complete was carried out for studies
      that evaluated the effectiveness of educational interventions. Forty eligible
      studies were identified. There were three types of educational interventions
      (Educational condition, Video-based Contact condition and Contact condition).
      Eighteen of 23 studies reported significant improvements in knowledge, 27 of 34
      studies yielded significant changes in attitudes towards people with mental
      illness. Significant effects in social distance were found in 16 of 20 studies.
      Two of five studies significantly improved young people's awareness of mental
      illness. However, six studies reported difficulties in maintaining improved
      knowledge, attitudes and social distance in young people. Furthermore, the
      majority of studies did not measure the actual behavioral change. From the
      comparison of the three types of educational interventions, direct contact with
      people with mental illness (Contact condition) seems to be key in reducing
      stigmatization, while the components of Education and Video-based contact
      conditions are still arguable. Despite the demonstration of the positive effects
      of each educational intervention, their long-term effects are still unclear.
      Further research needs to involve measuring actual behavioral change and
      performing a long-term follow up.

PMID- 21851450
TI  - Perceived burden and quality of life of caregivers in obsessive-compulsive
      disorder.
AB  - AIM: The study aimed to examine the family burden and quality of life (QOL) of
      caregivers of patients with obsessive-compulsive disorder (OCD). METHODS: A cross
      sectional assessment of 50 patients with OCD and their caregivers was carried
      out. The severity of OCD was assessed using the Yale-Brown Obsessive Compulsive
      Scale. The caregivers were assessed using the Family Burden Interview Schedule
      and the World Health Organization Quality of Life BREF version (WHOQOL-BREF).
      RESULTS: Fifty-six percent of caregivers reported a high objective burden.
      Severity of illness correlated with burden and impaired QOL of caregivers. Age of
      patient, longer duration of illness and longer duration of treatment were
      predictive of poorer QOL of caregivers in the physical health domain. Greater
      objective burden, disruption of family leisure and interaction due to OCD led to
      significantly poorer QOL in all domains in caregivers. Higher financial burden,
      perception of poorer mental health, and higher subjective burden were predictive
      of poorer physical, general health and general and psychological QOL,
      respectively. CONCLUSIONS: The study provides important insights into the QOL and
      perceived burden of caregivers of OCD patients. It highlights the need for
      improving the quality of care not only for patients but also for primary
      caregivers.

PMID- 21851451
TI  - Obsessive-compulsive disorder with and without bipolar disorder.
AB  - AIM: Bipolar disorder (BD) is often comorbid with obsessive-compulsive disorder
      (OCD). In this study, we compared clinical profile and course of subjects with a
      primary diagnosis of OCD with and without BD. METHODS: We compared 34 subjects
      with primary diagnosis of OCD with BD and 57 subjects with a diagnosis of OCD
      without BD. Structured interview schedules, clinical rating scales, and
      information from clinical charts were utilized to assess patients. RESULTS: OCD
      with BD was characterized by: (i) an episodic course; (ii) a higher number of
      depressive episodes, greater suicidality and a higher rate of hospitalization;
      (iii) fewer pathological doubts and more miscellaneous compulsions; and (iv)
      poorer insight into obsessive-compulsive symptoms. CONCLUSIONS: Episodic course
      appears to be typical of OCD with BD. Bipolarity has a pathoplastic effect on OCD
      and it is possible that some forms of OCD and BD are pathophysiologically
      related. Bipolar OCD is associated with a higher rate of depressive episodes,
      higher suicidality and more frequent hospitalizations, suggesting greater
      morbidity. Long-term prospective follow-up studies and studies addressing
      pathophysiology and genetic basis are needed to understand the complexity of such
      comorbidity.

PMID- 21851452
TI  - Screening performance of K6/K10 and other screening instruments for mood and
      anxiety disorders in Japan.
AB  - AIMS: This study aimed to establish the screening performance and optimal cut-off
      points for the Japanese version of Kessler (K)6, K10 and the Depression and
      Suicide Screen (DSS). METHODS: A self-report questionnaire including K6, K10 and
      DSS, as well as the Center for Epidemiologic Studies - Depression Scale (CES-D),
      was administered to a random sample of community residents in Japan (non-cases, n
      = 147) and psychiatric outpatients diagnosed with mood or anxiety disorders
      according to DSM-IV (cases, n = 17). A receiver-operator characteristics (ROC)
      curve was drawn to estimate the area under the curve (AUC), the sensitivity, and
      specificity with the optimal cut-off points for K6, K10, and DSS, which were then
      compared with those of CES-D. The community sample was also asked to rate each
      measure on a scale from 'very easy' to 'very hard' to use. RESULTS: K6 and K10
      showed a high AUC (0.93-0.94), which was comparable to that of CES-D (0.95), but
      DSS showed a significantly smaller AUC (0.89) than CES-D (P < 0.05). The optimal
      cut-off points were estimated as 4/5 for K6, 9/10 for K10, and 1/2 for DSS. The
      sensitivity of these three scales was similar, but the specificity was lower for
      DSS than for the other two. K6, K10 and DSS were rated as being 'very easy' or
      'easy to use' significantly more than CES-D (P < 0.01). CONCLUSION: The screening
      performance of the Japanese versions of K6 and K10 was comparable with that of
      CES-D, and better than that of DDS. K6/K10, particularly K6, might have an
      advantage, even over the CES-D, because of its similar screening performance and
      better acceptability.

PMID- 21851453
TI  - Cost of depression among adults in Japan in 2005.
AB  - AIM: Major depression is expected to become the leading contributor to disease
      burden worldwide by 2020. Previous studies have shown that the societal cost of
      depression is not less than that of other major illnesses, such as cardiovascular
      diseases or AIDS. Nevertheless, the cost of depression in Japan has never been
      examined. The goal of the present study was to estimate the total cost of
      depression in Japan and to clarify the characteristics of this burden. METHODS: A
      prevalence-based approach was adopted to measure the total cost of depression.
      The total cost of depression was regarded as being comprised of the direct cost,
      morbidity cost and mortality cost. Diagnoses included in this study were
      depressive episodes and recurrent depressive disorder according to the ICD-10 or
      major depressive disorder according to the DSM-IV. Data were collected from
      publicly available statistics and the World Mental Health Japan Survey database.
      RESULTS: The total cost of depression among adults in Japan in 2005 was estimated
      to be Y2.0 trillion. The direct cost was Y0.18 trillion. The morbidity cost was
      Y0.92 trillion, while the mortality cost was Y0.88 trillion. CONCLUSION: The
      societal costs caused by depression in Japan are enormous, as in other developed
      countries. Low morbidity costs and extremely high mortality costs are
      characteristic in Japan. Effective interventions for preventing suicide could
      reduce the societal costs of depression.

PMID- 21851454
TI  - Heart rate reactivity and current post-traumatic stress disorder when data are
      missing.
AB  - AIMS: This study demonstrates that auxiliary and exclusion criteria variables
      increase the effectiveness of missing imputation in correcting underestimation of
      physiologic reactivity in relation to post-traumatic stress disorder (PTSD)
      caused by deleting cases with missing physiologic data. METHODS: This study used
      data from survivors of the 1995 Oklahoma City bombing and imputed missing heart
      rate data using auxiliary and exclusion criteria variables. Logistic regression
      was used to examine heart rate reactivity in relation to current PTSD. RESULTS:
      Of 113 survivors who participated in the bombing study's 7-year follow-up
      interview, 42 (37%) had missing data on heart rate reactivity due to exclusion
      criteria (medical illness or use of cardiovascular or psychotropic medications)
      or non-participation. Logistic regression results based on imputed heart rate
      data using exclusion criteria and auxiliary (the presence of any current PTSD
      arousal symptoms) variables showed that survivors with current bombing-related
      PTSD had significantly higher heart rates at baseline and recovered more slowly
      back to baseline heart rate during resting periods than survivors without current
      PTSD, while results based on complete cases failed to show significant
      correlations between current PTSD and heart rates at any assessment points.
      CONCLUSIONS: Suggested methods yielded an otherwise undetectable link between
      physiology and current PTSD.

PMID- 21851456
TI  - Remission in schizophrenia: a community-based 6-year follow-up study in Bali.
AB  - AIM: The purpose of this naturalistic study was to investigate the rate and
      predictors of remission at medium-term follow up of individuals with
      schizophrenia in a community setting in Bali. METHODS: Subjects comprised 37
      individuals with schizophrenia, including 19 never-treated cases, screened from
      8546 general residents. Outcome was evaluated using the standardized symptomatic
      remission criteria based on Positive and Negative Syndrome Scale scores and
      operational functional remission criteria at 6-year follow up. RESULTS: Ten
      individuals (27%) achieved symptomatic remission, 12 (32%) achieved functional
      remission, and 10 (27%) achieved complete remission (i.e. symptomatic and
      functional remission). Lower Positive and Negative Syndrome Scale negative
      symptom score at baseline and receipt of psychiatric treatment for more than half
      of the follow-up period were predictors of complete remission. CONCLUSIONS: The
      majority of community-screened individuals with schizophrenia failed to achieve
      complete remission at the 6-year follow up. These results suggest that strategies
      promoting mental health service utilization among individuals with schizophrenia
      are essential in Bali.

PMID- 21851455
TI  - Successful aging in individuals with schizophrenia dwelling in the community: a
      study on attitudes toward aging and preparing behavior for old age.
AB  - AIM: 'Successful aging' in individuals with schizophrenia has been attracting
      attention. We examined two forward-looking factors of successful aging among
      schizophrenia patients: 'attitude toward aging' and 'preparing behavior for old
      age'. METHODS: Fifty-seven middle-aged and elderly schizophrenia patients with
      successful aging were identified using the Attitude toward Aging Scale, the
      Preparing Behavior for Old Age Scale, and assessments of their cognitive
      function, psychiatric symptoms, social functioning and quality of life. A
      multiple regression analysis was used to detect determinants of attitude toward
      aging/preparing behavior for old age at that time ('present': community
      dwelling). We also analyzed predictors of successful aging using
      demographic/clinical data assessed 3 years previously ('past': residential care).
      RESULTS: The multiple regression analysis revealed that quality of life was a
      significant determinant: a higher quality of life was related to a more positive
      attitude toward aging and less active preparing behavior. The significant
      predictors of preparing behavior were quality of life and the length of the
      hospital stay: a longer hospital stay and a higher quality of life were related
      to less active preparing behavior. CONCLUSION: Quality of life and the length of
      the hospital stay significantly contributed to forward-looking factors of
      successful aging. Avoiding long hospitalization periods for patients with
      schizophrenia may lead to more active preparing behavior, but the improvement of
      quality of life may not be a sufficient condition. As schizophrenia patients have
      an optimistic attitude and insufficient preparing behavior, support to prepare
      such individuals for old age is required as part of community-based psychiatric
      care strategies.

PMID- 21851457
TI  - Sexually dimorphic distribution of orbitofrontal sulcogyral pattern in
      schizophrenia.
AB  - AIM: The sulcogyral pattern of the orbitofrontal cortex (OFC) is characterized by
      a remarkable inter-individual variability that likely reflects neurobehavioral
      traits and genetic aspects of neurodevelopment. The aim of the present study was
      to evaluate the OFC sulcogyral pattern of patients with schizophrenia (SZ) and
      healthy controls (HC) to determine group differences in OFC sulcogyral pattern as
      well as gender differences between groups. METHODS: Forty-seven SZ patients (M/F,
      23/24) and forty-seven HC (M/F, 17/30), matched on age and gender, were analyzed
      using magnetic resonance imaging. The sulcogyral pattern was classified into type
      I, II, or III based on the guidelines set by Chiavaras and Petrides in a previous
      paper. Chi-squared analysis was used to investigate group and gender differences
      in the sulcogyral pattern distribution, and categorical regression was used to
      explore clinical correlations. RESULTS: The distribution of OFC sulcogyral
      pattern in HC replicated the results found in the previous study (left, chi(2) =
      0.02, P = 0.989; right, chi(2) = 0.97, P = 0.616), in that there were no gender
      differences. Moreover, the distribution in SZ-M was in accordance with that in
      the previous study (left, chi(2) = 1.59, P = 0.451; right, chi(2) = 0.14, P =
      0.933). Additionally, within SZ-M, patients with the type III pattern had a
      higher total positive and negative syndrome scale score (beta = 0.902, F = 14.75,
      P = 0.001). In contrast, the distribution in the right hemisphere in the SZ-F
      group differed significantly from that observed in SZ-M (chi(2) = 6.017, P =
      0.046), but did not differ from HC (chi(2) = 2.557, P = 0.110). CONCLUSION: OFC
      sulcogyral pattern is altered in SZ-M but not in SZ-F, possibly reflecting gender
      differences in early neurodevelopment.

PMID- 21851458
TI  - Factors related to readmission to a ward for dementia patients: sex differences.
AB  - AIM: The aim of this study was to investigate the factors related to readmission
      to a ward for dementia patients with special attention to sex-related issues.
      METHODS: We reviewed the data of 326 patients who were hospitalized in a ward for
      dementia patients between 1 April 2000 and 31 March 2008, and followed up for 24
      months after discharge. For univariate and multivariate analyses, patients were
      divided into: (i) patients who were not readmitted to our ward within 24 months
      (control); (ii) patients who were readmitted to our ward within 3 months (early
      readmission); and (iii) patients readmitted within 4 to 24 months (late
      readmission). RESULTS: Factors related to readmission differed between sexes as
      well as between the early and late stage. A small number of cohabitants and
      outcome (hospital) were factors related to early readmission in men, while
      outcome (hospital) and long stay in the ward were related to early readmission in
      women. High physical function, care distress and short stay in the ward were the
      factors related to late readmission in women. CONCLUSIONS: Most patients who were
      transferred to another hospital were readmitted within 3 months. Some women were
      readmitted in the late stage. They had relatively high cognitive and physical
      functions and most of their caregivers had care distress. The causes of
      readmission were not due to a decline in cognitive function. It is important to
      prevent complications in dementia patients and to establish a caregiving system
      for dementia patients that decreases the burden on caregivers in order to reduce
      the rate of readmission.

PMID- 21851459
TI  - Tachyphylaxis/tolerance to antidepressants in treatment of dysthymia: results of
      a retrospective naturalistic chart review study.
AB  - AIM: The main goals of this chart-review study were to examine the rate of
      tachyphylaxis during treatment of dysthymia with antidepressants, to compare the
      incidence of tolerance during trials of selective serotonin reuptake inhibitors
      (SSRI) and non-SSRI and to give descriptive analysis of the cases of
      tachyphylaxis. METHODS: The retrospective naturalistic chart review study
      included 52 cases of successfully treated (with different antidepressants)
      patients suffering from dysthymia. The overall number of the cases of tolerance
      to antidepressants were registered as well as the rate of these phenomena in the
      groups treated with SSRI and non-SSRI. RESULTS: The cases of
      tolerance/tachyphylaxis were observed in 12 patients (23% of patients) and in 13
      trials (22.4% of trials). All cases of tolerance occurred during monotherapy. No
      cases of tachyphylaxis were observed in the non-SSRI group while in the SSRI
      group, tolerance at some stage of the treatment was detected in 41.9% of the
      successful cases (P < 0.001). CONCLUSION: During the treatment of dysthymia with
      antidepressants in the SSRI group, tachyphylaxis/tolerance might be observed in a
      relatively in high proportion of cases.

PMID- 21851460
TI  - Predictors of fluoxetine remission for hospitalized patients with major
      depressive disorder.
AB  - AIM: The goal of treating major depressive disorder is to achieve remission. This
      prospective study aimed to identify predictors of remission in a cohort of
      depressive inpatients who received fluoxetine. METHODS: A total of 131 newly
      hospitalized patients with major depressive disorder received a fixed dose of 20
      mg/day (the recommended dose from the literature) of fluoxetine for 6 weeks.
      Symptom severity was assessed using the 17-item Hamilton Depression Rating Scale
      at weeks 0, 1, 2, 3, 4 and 6. Remission was defined as a score of <=7 on the 17
      item Hamilton Depression Rating Scale after 6 weeks of treatment. We compared the
      remitters and non-remitters in terms of baseline variables. The Short-Form-36
      pain interference item was used to assess pain. It was classified as high (score
      >= 3) or low (score < 3). RESULTS: A total of 31 (27.7%) of 112 completers
      remitted after 6 weeks of treatment. The remitters and non-remitters did not
      differ in baseline variables, except pain interference, baseline depression
      severity, and depression improvement at week 1. CONCLUSION: These findings
      obtained from newly hospitalized major depression patients support the previous
      notion that pain interference, depression severity, and early improvement can be
      the predictors for remission. Patients with high pain interference, a greater
      depression severity or a less early improvement are likely to require aggressive
      treatment early. These data require confirmation and extension to outpatients and
      other antidepressants.

PMID- 21851461
TI  - Coagulation activation and fibrinolysis impairment are reduced in patients with
      anxiety and depression when medicated with serotonergic antidepressants.
AB  - AIMS: Anxiety disorders have been shown to be correlated with an activation of
      coagulation and impairment of fibrinolysis. The aim of the study was to assess
      whether medication with a serotonergic antidepressant, which has been associated
      with abnormal bleeding, may modify this effect. METHODS: Thirty-one anxiety
      patients, mostly with comorbid depression, and 31 healthy controls were included
      in the study. Group differences between anxiety patients medicated with a
      serotonergic antidepressant, patients without serotonergic antidepressant and
      controls were assessed for activated partial thromboplastin time, fibrinogen,
      factor VII, factor VIII, von Willebrand factor, von Willebrand ristocetin
      cofactor activity, prothrombin fragment 1 + 2, thrombin-antithrombin complex, d
      dimer, alpha2-antiplasmin, plasmin-alpha2-antiplasmin complex (PAP), tissue
      plasminogen activator and plasminogen activator inhibitor. Intervening variables,
      such as age, sex, body mass index and smoking, were accounted for. RESULTS: We
      found lower coagulation measures for fibrinogen (P = 0.03) and plasminogen
      activator inhibitor (P = 0.01), and higher levels of PAP (P = 0.046) in patients
      with serotonergic antidepressant than in patients without serotonergic
      antidepressant. When controlling for smoking and body mass index, differences
      between the two groups were significant for PAP (P = 0.02), von Willebrand
      ristocetin cofactor activity (P = 0.02) and activated partial thromboplastin time
      (P = 0.046). Coagulation scores were similar in patients with serotonergic
      antidepressant to those of healthy controls. CONCLUSIONS: Serotonergic
      antidepressants may counteract a procoagulant effect of anxiety and/or depression
      in anxiety patients.

PMID- 21851462
TI  - Plasma substance P level in patients with schizophrenia: a cross-sectional study.
AB  - Aspiration pneumonia is a serious health concern in older patients with
      schizophrenia. In this study, we examined clinical and demographic variables that
      could impact the plasma substance P level, which is a useful predictive biomarker
      of aspiration. Thirty-four patients were included (mean age +/- SD: 70.9 +/- 10.8
      years). A greater number of cigarettes/day and a higher antipsychotic dosage were
      found to be associated with a lower plasma substance P level, while age showed a
      trend-level effect. This finding suggests the need for intensive observation for
      prevention of aspiration pneumonia in heavy smokers who are receiving a higher
      antipsychotic dose in this senior population.

PMID- 21851463
TI  - Comparative study of suicide risk in depressive disorder patients with and
      without problem drinking.
AB  - The present study sought to determine whether the co-occurrence of problem
      drinking heightens suicide risk in individuals with depression in Japan, using a
      sample of 784 outpatients (287 men and 497 women) with depressive disorder.
      Female subjects with at least a moderate problem drinking showed significantly
      more severe depression and suicidality than those without, but no such difference
      was identified in men.

PMID- 21851464
TI  - Utility of the Quality of Life-Alzheimer's Disease Scale for mild cognitive
      impairment.

PMID- 21851465
TI  - Diphenhydramine overdose mimicking serotonin syndrome.

PMID- 21851466
TI  - Necessity for ethical consideration of research in the aftermath of disaster.

PMID- 21851467
TI  - Patient with isolated adrenocorticotropic hormone (ACTH) deficiency who was
      depressive before glucocorticoid replacement, and exhibited stupor during
      continuous ACTH test.

PMID- 21851468
TI  - Case of alfacalcidol-induced hypercalcemia presenting as bipolar disorder.

PMID- 21851469
TI  - Concurrent pedal edema and sinus bradycardia associated with quetiapine.

PMID- 21851470
TI  - Occurrence of the parasite genus Hematodinium (Alveolata: Syndinea) in the water
      column.
AB  - Crustaceans worldwide are infected with alveolate parasites of the genus
      Hematodinium, causing substantial losses to langoustine and crab fisheries. The
      distinct seasonality in Hematodinium occurrence in their decapod hosts, as well
      as unsuccessful attempts at transmission, suggest the existence of life stages
      outside their benthic crustacean hosts. We used a nested polymerase chain
      reaction method to detect Hematodinium rDNA in the environment and in potential
      alternative hosts. Environmental samples from the Clyde Sea, Scotland, were
      screened during the April release of dinospores and during June and August, when
      infection prevalence is rare in benthic crustaceans. Hematodinium rDNA was
      amplified in 15% (14/94) of isolated langoustine larvae, and in 12% (13/111) of
      crab larvae. In addition, Hematodinium rDNA was present in mixed plankton samples
      devoid of decapod larvae, but including the 2 MUm-10 mm fraction of particulate
      organic matter in the water column, containing phytoplankton and other
      zooplankton. These results indicate that Hematodinium occurs in the water column
      and is harboured by planktonic organisms, including larval stages of the
      crustacean hosts, when infections are at their lowest in adult hosts.

PMID- 21851471
TI  - Sorosphaerula nom. n. for the plasmodiophorid genus Sorosphaera J. Schroter 1886
      (Rhizaria: Endomyxa: Phytomyxea: Plasmodiophorida).
AB  - Sorosphaerula nom. n. is introduced to replace the phytomyxean generic name
      Sorosphaera J. Schroter, which is preoccupied by the foraminiferan genus
      Sorosphaera Brady. As it is agreed now that both the Foraminifera and the
      Phytomyxea belong to the Rhizaria, this homonomy within the same supergroup of
      eukaryotes needs to be revised. To avoid future homonomy, we recommend that the
      International Code of Zoological Nomenclature be applied for future taxonomic
      work on Phytomyxea.

PMID- 21851472
TI  - A human neutralizing antibody specific to Ang-2 inhibits ocular angiogenesis.
AB  - OBJECTIVE: Angiogenesis, a critical contributor to ocular as well as neoplastic
      diseases, is stimulated by endothelial production of angiopoietin-2 (Ang2). Our
      objective was to determine the requirement of ocular angiogenesis for Ang2 in
      animal models of disease. METHODS: We developed and compared the effect of a
      novel human Ang2 antibody with a pan-angiopoietin strategy on angiogenesis in
      ocular angiogenesis in animal models of oxygen-induced retinopathy, and laser
      photocoagulation and confirmed its efficacy in xenografted human colorectal
      tumors. RESULTS: Human anti-Ang2 and anti-angiopoietin1(Ang1)/Ang2 antibodies
      blocked colorectal carcinoma growth in immuno-compromised mice (p < 0.001, n =
      6). Injection of 1 MUg of Ang2 or Ang2/Ang1 antibody-inhibited angiogenesis in
      models of retinal (p < 0.001, n = 6), and choroidal neovascularization (p <
      0.001, n = 11-13 per group) to levels similar to that with anti-VEGF antibodies.
      There was no difference between Ang2 specific and Ang1/Ang2 bi-specific
      antibodies. In vitro, Ang2 antibodies showed no cytotoxicity and did not inhibit
      endothelial cell migration or proliferation. CONCLUSION: Thus, human Ang2
      antibodies are potentially therapeutic agents for ocular neovascularization in
      models of retinal and choroidal neovascularization, in the absence of VEGF
      inhibition.

PMID- 21851473
TI  - Dynamic adaptation of the peripheral circulation to cold exposure.
AB  - Humans residing or working in cold environments exhibit a stronger cold-induced
      vasodilation (CIVD) reaction in the peripheral microvasculature than those living
      in warm regions of the world, leading to a general assumption that thermal
      responses to local cold exposure can be systematically improved by natural
      acclimatization or specific acclimation. However, it remains unclear whether this
      improved tolerance is actually due to systematic acclimatization, or alternately
      due to the genetic pre-disposition or self-selection for such occupations.
      Longitudinal studies of repeated extremity exposure to cold demonstrate only
      ambiguous adaptive responses. In field studies, general cold acclimation may lead
      to increased sympathetic activity that results in reduced finger blood flow.
      Laboratory studies offer more control over confounding parameters, but in most
      studies, no consistent changes in peripheral blood flow occur even after repeated
      exposure for several weeks. Most studies are performed on a limited amount of
      subjects only, and the variability of the CIVD response demands more subjects to
      obtain significant results. This review systematically surveys the trainability
      of CIVD, concluding that repeated local cold exposure does not alter circulatory
      dynamics in the peripheries, and that humans remain at risk of cold injuries even
      after extended stays in cold environments.

PMID- 21851474
TI  - No escape from a VSD device? Complete heart block and cardiac arrest associated
      with a ventricular septal defect occluder device.
AB  - A 15 month old boy with a ventricular septal defect (VSD) underwent percutaneous
      device closure of the VSD. Five days later he collapsed; on arrival to hospital
      he was asystolic and received prolonged cardio-pulmonary resuscitation (CPR) with
      intermittent return of spontaneous circulation (ROSC). He had recurrent episodic
      complete heart block with no ventricular escape rhythm, associated with loss of
      cardiac output, unresponsive to transcutaneous pacing. He was transferred to
      theatre, while receiving CPR, for urgent removal of the VSD device. Estimated
      total 'down time' was 70 min. The device was removed and patch closure of the VSD
      was performed. He made a full neurological recovery. Device closure of septal
      defects has become widespread. We discuss the incidence and type of arrythmias
      associated with their use. This case highlights an uncommon but life threatening
      complication of a VSD device. It also highlights that good quality CPR may lead
      to positive outcomes following pediatric cardiac arrest.

PMID- 21851475
TI  - Prevention for pediatric low cardiac output syndrome: results from the European
      survey EuLoCOS-Paed.
AB  - OBJECTIVE: Characterize current hospital practices related to preventive drug
      therapy for low cardiac output syndrome (LCOS) in children with open heart
      surgery (OHS) in Europe. METHODS: Web-based questionnaire survey of European
      hospitals performing OHS in children, conducted between January and August 2009.
      RESULTS: Responses to the questionnaire were obtained from 90 of 125 hospitals
      (72.0%) from 31 different countries across the geographical European regions. The
      majority of hospitals (77.8%) administered preventive drug therapy and primarily
      targeted patients at risk (63.3%). Twenty-four different drug regimens were
      reported, involving 17 drugs from seven therapeutic drug classes. Milrinone,
      dopamine, epinephrine, dobutamine, and levosimendan made up 85.9% of the total
      drug use. Furthermore, milrinone was reported in 70.7% of all drug regimens and
      significantly more often in combination with other drugs than monotherapy
      (Delta20%, 95% CI 4.7-34.1%). Milrinone combination therapy reports included
      lower bolus but higher maintenance infusion doses than monotherapy reports. The
      timing of drug regimen administration varied across the full perioperative
      period, but drug regimens were mostly initiated during surgery and continued
      postoperatively. CONCLUSION: Although current hospital practices related to
      preventive drug therapy for LCOS in children with OHS are characterized by a
      marked variability, only few drugs make up the bulk of prescribing practice with
      milrinone being most commonly used. Therefore, the survey provides information on
      which drugs to focus research and establish safe and effective drug use. A
      unified approach is urgently needed to ensure that children with OHS can benefit
      from evidence-based care.

PMID- 21851476
TI  - Predictive factors for difficult intravenous cannulation in pediatric patients at
      a tertiary pediatric hospital.
AB  - BACKGROUND: It is generally believed that certain patient characteristics (e.g.,
      Body Mass Index and age) predict difficulty of intravenous cannulation in
      children, but there is not much literature evaluating these risk factors. In this
      study, we investigated predictive factors for success rate at first attempt and
      time needed for intravenous cannulation. METHODS/MATERIALS: In a prospective
      cohort study, we observed characteristics of intravenous cannulations in
      pediatric patients at the operating room (n = 1083) and the outpatient care unit
      (n = 178) of a tertiary referral pediatric hospital. Time to successful
      intravenous cannulation, success at first attempt, and potential predictors for
      difficult cannulation (age, gender, skin color, BMI or weight-to-age z-score, the
      child being awake or anesthetized, operator profession and surgical specialty)
      were recorded. Regression models were constructed to find significant predictors.
      RESULTS: Success at first attempt was 73% and 81%, respectively. In the operating
      room age, operator and surgical specialty were predictive for a successful first
      attempt and time to successful cannulation. No significant predictive factors
      were found for the outpatient care unit. BMI or weight-to-age was not related to
      difficult intravenous cannulation. CONCLUSIONS: This study shows that in one
      fifth to one-third of the patients, intravenous cannulation required more than
      one attempt. It is difficult to predict with accuracy the difficulty of
      intravenous cannulation solely with easily obtainable patient characteristics.

PMID- 21851478
TI  - Microbiological diagnosis of prosthetic joint infections: a prospective
      evaluation of four bacterial culture media in the routine laboratory.
AB  - The diagnosis of prosthetic joint infection (PJI) in the routine microbiology
      laboratory is labour-intensive, but semi-automated methods may be appropriate. We
      prospectively compared four microbiological culture methods on samples taken at
      prosthetic joint revision surgery. Automated BACTEC blood culture bottles and
      cooked meat enrichment broth were the most sensitive methods (87% and 83%,
      respectively, as compared with fastidious anaerobic broth (57%) and direct plates
      (39%)); all were highly specific (97-100%). To our knowledge, this is the first
      prospective study aimed at comparing culture methods in routine use in UK
      clinical laboratories for the diagnosis of PJI.

PMID- 21851477
TI  - Human infection with novel G3P[25] rotavirus strain in Taiwan.
AB  - Genotype P[25] rotaviruses are rare and to date have been reported to occur only
      in a few countries of mainland Asia. Here we report the molecular
      characterization of a novel human rotavirus genotype combination, G3P[25],
      detected in a 17-month-old child hospitalized due to severe gastroenteritis
      during 2009 in central Taiwan. Sequencing and phylogenetic analysis of the VP4
      gene demonstrated a distinct origin from other strains bearing the P[25] VP4
      gene, whereas the VP7, VP6 and NSP4 gene phylogenies identified common origins
      with cognate genes of other, presumed human-porcine reassortment Taiwanese
      strains. These results suggest that interactions between human and animal strains
      appear to contribute to the generation of genetic and antigenic diversity of
      rotavirus strains, with potential public health importance in Taiwan.

PMID- 21851479
TI  - Invasive fungal infection in an elderly patient with defective inflammatory
      macrophage function.
AB  - Macrophages are known to be involved in pathogen recognition and mediate host
      immune responses, but, in the clinical setting, their purported central role in
      opportunistic fungal infections has not been demonstrated to date. Herein, we
      describe a patient with invasive testicular aspergillosis in whom we found, for
      the first time, a defect in macrophage function.

PMID- 21851481
TI  - Viruses and bacteria in sputum samples of children with community-acquired
      pneumonia.
AB  - Few comprehensive studies have searched for viruses and bacteria in children with
      community-acquired pneumonia (CAP). We identified 76 children hospitalized for
      pneumonia. Induced sputum samples were analysed for 18 viruses by antigen
      detection and PCR, and for six bacteria by culture and PCR. Viruses were found in
      72% of samples, bacteria in 91%, and both in 66%. Rhinovirus (30%), human
      bocavirus (18%) and human metapneumovirus (14%) were the most commonly detected
      viruses. Two viruses were found in 22% of samples and three in 8%. The most
      common bacteria found were Streptococcus pneumoniae (50%), Haemophilus influenzae
      (38%), and Moraxella catarrhalis (28%). Rhinovirus-S. pneumoniae was the most
      commonly found combination of virus and bacterium (16%). All six children with
      treatment failure had both viruses and bacteria detected in the sputum.
      Otherwise, we found no special clinical characteristics in those with mixed viral
      bacterial detections. With modern molecular diagnostic techniques, there are high
      rates of both viral and bacterial identification in childhood CAP. The clinical
      significance of mixed viral-bacterial infections remains unclear, although we
      found a potential association between them and treatment failure.

PMID- 21851480
TI  - Clonal dissemination of Klebsiella pneumoniae ST258 harbouring KPC-2 in
      Argentina.
AB  - The present work describes the abrupt emergence of Klebsiella pneumoniae
      carbapenemase (KPC) and characterizes the first 79 KPC-producing enterobacteria
      from Argentina (isolated from 2006 to 2010). The emergence of bla(KPC-2) was
      characterized by two patterns of dispersion: the first was the sporadic
      occurrence in diverse enterobacteria from distant geographical regions,
      harbouring plasmids of different incompatibility groups and bla(KPC-2) in an
      unusual genetic environment flanked by ISKpn8-Deltabla(TEM-1) and ISKpn6-like.
      bla(KPC-2) was associated with IncL/M transferable plasmids; the second was the
      abrupt clonal spread of K. pneumoniae ST258 harbouring bla(KPC-2) in Tn4401a.

PMID- 21851482
TI  - The impact of multidrug resistance in healthcare-associated and nosocomial Gram
      negative bacteraemia on mortality and length of stay: cohort study.
AB  - Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging public
      health threat. Accurate estimates of their clinical impact are vital for
      justifying interventions directed towards preventing or managing infections
      caused by these pathogens. A retrospective observational cohort study was
      conducted between 1 January 2007 and 31 July 2009, involving subjects with
      healthcare-associated and nosocomial Gram-negative bacteraemia at two large
      Singaporean hospitals. Outcomes studied were mortality and length of stay post
      onset of bacteraemia in survivors (LOS). There were 675 subjects (301 with MDR
      GNB) matching study inclusion criteria. On multivariate analysis, multidrug
      resistance was not associated with 30-day mortality, but it was independently
      associated with longer LOS in survivors (coefficient, 0.34; 95% CI, 0.21-0.48; p
      < 0.001). The excess LOS attributable to multidrug resistance after adjustment
      for confounders was 6.1 days. Other independent risk factors for higher mortality
      included male gender, higher APACHE II score, higher Charlson comorbidity index,
      intensive care unit stay and presence of concomitant pneumonia. Concomitant
      urinary tract infection and admission to a surgical discipline were associated
      with lower risk of mortality. Appropriate empirical antibiotic therapy was
      neither associated with 30-day mortality nor LOS, although the study was not
      powered to assess this covariate adequately. Our study adds to existing evidence
      that multidrug resistance per se is not associated with higher mortality when
      effective antibiotics are used for definitive therapy. However, its association
      with longer hospitalization justifies the use of control efforts.

PMID- 21851483
TI  - Visceral leishmaniasis: immunology and prospects for a vaccine.
AB  - Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum
      of neglected tropical diseases caused by protozoan parasites of the genus
      Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts
      for more than 50 000 deaths every year. Drug therapy is available but costly, and
      resistance against several drug classes has evolved. Here, we review our current
      understanding of the immunology of HVL and approaches to and the status of
      vaccine development against this disease.

PMID- 21851484
TI  - An algorithm based on one or two nasal samples is accurate to identify persistent
      nasal carriers of Staphylococcus aureus.
AB  - Persistent Staphylococcus aureus nasal carriers are at high risk of S. aureus
      infection. The present study delineates a simple strategy aimed at identifying
      rapidly and accurately this subset of subjects for clinical or epidemiological
      purposes. Ninety healthy volunteers were each identified as persistent,
      intermittent or non-nasal carriers of S. aureus by using seven specimens sampled
      over a 5-week period. By reference to this so-called reference standard, six
      other strategies aimed at simplifying and speeding the identification of
      persistent carriers and based on the qualitative or quantitative detection of S.
      aureus in one to three nasal samples were evaluated by the measure of the area
      under the curve of receiver operating characteristic diagrams. Among strategies
      using qualitative results, there was no statistical difference between protocols
      using seven and three samples. A threshold of 10(3) CFU of S. aureus per swab was
      found capable of defining persistent nasal carriage with a sensitivity of 83.1%
      and a specificity of 95.6%. These figures reached 95.5% and 94.9%, respectively,
      by using an algorithm including one or two nasal specimens according to the
      threshold of 10(3) CFU of S. aureus in the first swab. The latter two strategies
      were shown to be costly equivalents. The proposed algorithm-based strategy proved
      to be relevant to identify properly and consistently persistent nasal carriers of
      S. aureus. However, as it was built from data of healthy volunteers, it needs to
      be confirmed prospectively on patients potentially at risk for S. aureus
      infection.

PMID- 21851485
TI  - Contemporary unconventional clinical use of co-trimoxazole.
AB  - In the late 1960s, the combination of trimethoprim and sulphamethoxazole (co
      trimoxazole) was introduced into clinical practice and used to treat many
      infectious diseases, such as urinary tract infections, respiratory infections,
      sexually transmitted diseases, Gram-negative sepsis, enteric infections and
      typhoid fever. Subsequently, co-trimoxazole was reported to be effective against
      numerous bacterial, fungal and protozoal pathogens, including Nocardia, Listeria
      monocytogenes, Brucella, Stenotrophomonas maltophilia, Burkholderia, Coxiella
      burnetii, Tropheryma whipplei, atypical mycobacteria, and Pneumocystis jirovecii.
      Among protozoal infections, in addition to toxoplasmosis, co-trimoxazole has been
      used to treat susceptible Plasmodium falciparum, Cyclospora and Isospora
      infections. Several retrospective and prospective studies have demonstrated good
      clinical outcome with co-trimoxazole in treating invasive methicillin-resistant
      Staphylococcus aureus infections. We summarize herein the accumulated evidence in
      the literature on the new, 'unconventional' clinical use of co-trimoxazole during
      the last three decades. In the era of widespread antibiotic resistance and
      shortage of new antibiotic options, large-scale, well-designed studies are needed
      to explore the tremendous potential concealed in this well-established drug.

PMID- 21851486
TI  - Antimicrobial treatment of invasive non-perinatal human listeriosis and the
      impact of the underlying disease on prognosis.
AB  - Listeriosis is a resurgent foodborne disease in European countries. Benefits of
      combined beta-lactam-aminoglycoside treatment remain controversial and the impact
      of the underlying disease on prognosis has not been fully assessed. We conducted
      a retrospective review of cases of sporadic listeriosis in adults from 1995 to
      2008 at two university-affiliated hospitals serving a population of 600,000
      people in Madrid, Spain. The primary end-point was the associated in-hospital
      mortality. Sixty-four patients were studied. Estimated incidence of listeriosis
      was 0.76/100.000 persons/year. Seventy-four per cent had chronic underlying
      diseases; cirrhosis of the liver and haematological and solid neoplasias were the
      most common comorbidities. Primary bacteraemia (58%) and meningitis (42%) were
      the most frequent manifestations. Focal infections were seen in ten cases. In
      hospital mortality was 31%. Patients treated with ampicillin or with an
      ampicillin-gentamicin combination did not differ in age, severity of underlying
      disease or type of presentation. Differences in mortality were not seen between
      patients treated with monotherapy and those given combined treatment (28% vs 35%;
      p 0.634). Ten patients were treated with trimethoprim-sulfamethozaxole alone and
      only one died. All patients without comorbidities survived infection but
      mortality of patients with cirrhosis of the liver was 21% and that of patients
      with haematological or solid neoplasias was 66%. Only haematological neoplasia
      (OR 6.67; 95% CI 1.71-26.04; p 0.006) was significantly associated with an
      increased risk of mortality (R(2) (Cox-Snell) = 0.262). Mortality of listeriosis
      mainly depended on the severity of the underlying disease. Combined ampicillin
      gentamicin therapy did not improved survival. Trimethoprim-sulfamethozaxole may
      be an effective alternative therapy for listerial infections.

PMID- 21851487
TI  - First influenza season after the 2009 pandemic influenza: characteristics of
      intensive care unit admissions in adults and children in Vall d'Hebron Hospital.
AB  - To assess potential differences in epidemiology and management of patients
      admitted with influenza infection in the intensive care unit (ICU) during the
      first post-pandemic influenza period. Observational prospective study comparing
      September 2009-January 2010 with September 2010-January 2011. Variables captured:
      demographics, co-morbidities, physiological parameters, outcomes and management.
      Analysis was performed using SPSS v. 13.0; significance was set at p 0.5. Data
      from 53 patients, 38 adults (age, median 41.5 years; interquartile range (IQR)
      32.8-51.3) and 15 children (age, median 2 years, IQR 0.5-9) are presented.
      Vaccination rates were 0% and 4.3% during the first and second periods,
      respectively. Differences postpandemic were: 100% of episodes developed after
      December compared with 16.7% in the 2009 season. Younger children were affected
      (median age 0.8 years (IQR 0.3-4.8) vs 7 years (IQR 1.25-11.5), p 0.05) and
      influenza B caused 8.7% of ICU admissions. Influenza A (H1N1) 2009 and
      respiratory syncytial virus epidemics occurred simultaneously (42.8% of children)
      and bacterial co-infections doubled (from 10% to 21.7%); the prevalence of co
      infections (viral or bacterial) increased from 10% to 39.1% (OR 5.8, 95% CI 1.3
      24.8). Respiratory syndromes without chest X-ray opacities reflecting
      exacerbation of asthma or chronic obstructive pulmonary disease, bronchitis or
      bronchiolitis increased (from 6.9% to 39.1%, p<0.05) and pneumonia decreased
      (from 83.3% to 56.5%, p <0.05). Primary viral pneumonia predominated among ICU
      admissions. Postpandemic ICU influenza developed later, with some cases of
      influenza B, more frequent bacterial and viral co-infections and more patients
      with severe acute respiratory infection with normal chest X-ray. Increasing
      vaccination rates among risk-group individuals is warranted to prevent ICU
      admission and death.

PMID- 21851488
TI  - Infections in traumatic brain injury patients.
AB  - Traumatic brain injury (TBI) victims are considered to be at high risk for
      infection. The purpose of this cohort study was to delineate the rates, types and
      risk factors for infection in TBI patients. Retrospective surveillance of
      infections was conducted for all TBI patients, aged >=18 years, cared for at the
      Department of Neurosurgery of the University Hospital of Heraklion, Greece,
      between 1999 and 2005. A total of 760 patients (75% men) with a median age of 41
      years were included. Most (59%) were injured in a motor vehicle accident. One
      third of them underwent a surgical procedure. Two hundred and fourteen infections
      were observed. The majority were infections of the lower respiratory tract (47%),
      followed by surgical site infections (SSI) (17%). Multivariate analysis showed
      that SSI development was independently associated with the performance of >=2
      surgical procedures (OR 16.7), presence of concomitant infections, namely VAP (OR
      5.7) and UTI (OR 8.8), insertion of lumbar (OR 34.5) and ventricular drains (OR
      4.0), and cerebrospinal fluid (CSF) leak (OR 3.8). Development of meningitis was
      associated with prolonged hospitalization (OR 1.02), especially >7 days ICU stay
      (OR 25.5), and insertion of lumbar (OR 297) and ventricular drains (OR 9.1).
      There was a notable predominance of Acinetobacter spp. as a VAP pathogen; gram
      positive organisms remained the most prevalent in SSI cases. Respiratory tract
      infections were the most common among TBI patients. Device-related communication
      of the CSF with the environment and prolonged hospitalization, especially in the
      ICU setting, were independent risk factors for SSIs and meningitis cases.

PMID- 21851489
TI  - Time to liquid culture positivity can substitute for colony counting on agar
      plates in early bactericidal activity studies of antituberculosis agents.
AB  - The measurement of early bactericidal activity (EBA) is the first step in the
      clinical investigation of antituberculosis agents. EBA is determined by
      quantifying the viable sputum mycobacterial load on consecutive days of
      treatment. To investigate whether time to positivity (TTP) in mycobacterial
      liquid culture can substitute for colony forming unit (CFU) counting on agar
      plates we compared the error variation of TTP and CFU in 2115 pooled sputum
      samples collected overnight from 250 individuals included in five EBA studies. We
      found that the technical variation between duplicate laboratory measurements and
      the within-subject or day-to-day variation were similar for TTP (8.5% and 27.4%
      of total variation, respectively) and CFU (6.7% and 29.3% of total variation).
      The ability of the measurements to separate the EBA of 22 treatment arms was
      determined with group rank correlation of means and one-way analysis of variance.
      Except for the EBA over 0-2 days, individual and group EBAs measured with TTP and
      CFU were highly correlated. Treatment group means rank correlation coefficients
      were r=0.472, r=0.910 and r=0.818, respectively, for EBA 0-2 days, EBA 0-7 days
      and EBA 0-14 days. Analysis of variance significantly favoured TTP over CFU for
      discrimination between groups with F values of 6.58 and 1.87, 7.77 and 4.58, and
      8.71 and 3.56, respectively. We conclude that TTP is an acceptable alternative to
      CFU counting for the determination of the viable sputum mycobacterial load in EBA
      studies of up to 14 days duration.

PMID- 21851490
TI  - Failure to elicit seroresponses to pneumococcal surface proteins (pneumococcal
      histidine triad D, pneumococcal choline-binding protein A, and serine proteinase
      precursor A) in children with pneumococcal bacteraemia.
AB  - Pneumococcal surface proteins (PSPs) elicit antibody responses in infants and
      young children exposed to Streptococcus pneumoniae. These seroresponses could
      contribute to the aetiological diagnosis of pneumococcal disease, e.g. during the
      clinical development of novel PSP-based vaccines. In this study, we assessed the
      kinetics of antibody responses to three highly conserved and immunogenic PSPs
      (pneumococcal histidine triad D (PhtD), pneumococcal choline-binding protein A
      (PcpA), and serine proteinase precursor A (PrtA)) in 106 children (median age,
      21.3 months; males, 58.5%) admitted for pneumococcal bacteraemia. Anti-PhtD, anti
      PcpA and anti-PrtA antibodies were measured by ELISA, and compared in 61 pairs of
      acute (<=7 days) and convalescent (>14 days of admission) serum samples. Acute
      serum titres were similar to those observed in healthy children, and were
      unaffected by the acid dissociation of circulating immune complexes. Despite
      proven bacteraemia, seroresponses (>=2-fold increase in anti-PSP antibody
      concentrations) were only identified in 31 of 61 children (50.8%), directed
      against PrtA (n = 23, 37.7%), PcpA (n = 19, 31.1%), and PhtD (n = 16, 26.2%), or
      several PSPs (two PSPs, n = 13, 21.3%; three PSPs, n = 7, 11.5%). Certain
      seroresponses were very strong (maximal fold-increases: PhtD, 26; PcpA, 72; PrtA,
      12). However, anti-PSP antibody concentrations failed to increase in the
      convalescent sera of 30 of 61 (49.2%) bacteraemic children, and even declined
      (>=2 fold) in 13 of 61 (21.3%), mostly infants aged <6 months (8/13, 61.5%),
      possibly through consumption of maternal antibodies. Thus, pneumococcal
      bacteraemia may fail to elicit antibody responses, and may even have an antibody
      depleting effect in infants. This novel observation identifies an important
      limitation of serology-based studies for the identification of bacteraemic
      children.

PMID- 21851491
TI  - Can a spuriously raised creatinine by Jaffe method be helpful in poisoning?

PMID- 21851492
TI  - A rare cause of cardiac syncope mimicking epilepsy: left main coronary artery
      stenosis.

PMID- 21851493
TI  - A case of D-bifunctional protein deficiency: clinical, biochemical and molecular
      investigations.

PMID- 21851494
TI  - Miller syndrome with novel dihydroorotate dehydrogenase gene mutations.

PMID- 21851495
TI  - Congenital anterior neck cysts classified as 'thyroglossal anomalies'.

PMID- 21851496
TI  - Conservative treatment of spontaneous biliary perforation.

PMID- 21851497
TI  - Calcified catheter "cast" in child after treatment for acute lymphoblastic
      leukemia.

PMID- 21851498
TI  - Successful treatment of childhood Philadelphia chromosome-positive acute myeloid
      leukemia.

PMID- 21851499
TI  - Contralateral pleural recurrence of adrenocortical carcinoma after surgical
      resection.

PMID- 21851500
TI  - Mid-aortic syndrome in a preterm infant.

PMID- 21851501
TI  - Image of dermoid cyst in infant.

PMID- 21851502
TI  - Usefulness of measurement of urinary N-terminal pro-brain natriuretic peptide in
      neonatal period.

PMID- 21851503
TI  - Aberrant splicing by a mutation, c.403+2T>A, in Korean patients with
      arthrogryposis-renal-dysfunction-cholestasis syndrome.

PMID- 21851504
TI  - Atypical case of X-linked agammaglobulinemia diagnosed at 45 years of age.

PMID- 21851507
TI  - Risk of inhibitor development in mild haemophilia A increases with age.
AB  - Mild haemophilia A is a rare disease with a relatively mild phenotype. Treatment
      with factor VIII (FVIII) is indicated after trauma or for surgery only. FVIII
      infusion may result in the development of inhibiting antibodies against FVIII.
      This study describes the relation between age and other risk factors for
      inhibitor development in mild haemophilia. A retrospective cohort study was
      conducted among all patients with mild haemophilia (FVIII 0.05-0.40 IU mL(-1))
      registered at the van Creveldkliniek, University Medical Centre Utrecht, The
      Netherlands. Data on peak treatment with FVIII, gene mutation and history of
      inhibitor development were obtained from patient files from the period between
      1st January 1970 and 31st December 2009. A total of 231 out of 297 (78%) patients
      had at least one exposure to FVIII, of whom 14 (6.1%) developed an inhibitor to
      FVIII at a median age of 66 years after a median of 50 exposure days (ED). Age at
      first exposure, age at peak treatment, number of peak treatments and Arg593Cys
      mutation were significantly associated with the development of an inhibitor,
      while continuous infusion with FVIII was not. Although the incidence of
      inhibitors in mild haemophilia is low, it increases with age and peak treatments.
      With increasing age patients with mild haemophilia will suffer from co-morbidity
      more frequently, requiring surgical interventions and exposing them to an
      increased risk of inhibitor development. Especially patients with a change of
      arginine in cysteine at 593 are at risk for inhibitor development.

PMID- 21851506
TI  - Development of the vagal innervation of the gut: steering the wandering nerve.
AB  - BACKGROUND: The vagus nerve is the major neural connection between the
      gastrointestinal tract and the central nervous system. During fetal development,
      axons from the cell bodies of the nodose ganglia and the dorsal motor nucleus
      grow into the gut to find their enteric targets, providing the vagal sensory and
      motor innervations respectively. Vagal sensory and motor axons innervate
      selective targets, suggesting a role for guidance cues in the establishment of
      the normal pattern of enteric vagal innervation. PURPOSE: This review explores
      known molecular mechanisms that guide vagal innervation in the gastrointestinal
      tract. Guidance and growth factors, such as netrin-1 and its receptor, deleted in
      colorectal cancer, extracellular matrix molecules, such as laminin-111, and
      members of the neurotrophin family of molecules, such as brain-derived
      neurotrophic factor have been identified as mediating the guidance of vagal axons
      to the fetal mouse gut. In addition to increasing our understanding of the
      development of enteric innervation, studies of vagal development may also reveal
      clinically relevant insights into the underlying mechanisms of vago-vagal
      communication with the gastrointestinal tract.

PMID- 21851508
TI  - Licorice and its potential beneficial effects in common oro-dental diseases.
AB  - Licorice, the name given to the roots and stolons of Glycyrrhiza species, has
      been used since ancient times as a traditional herbal remedy. Licorice contains
      several classes of secondary metabolites with which numerous human health
      benefits have been associated. Recent research suggests that licorice and its
      bioactive ingredients such as glycyrrhizin, glabridin, licochalcone A,
      licoricidin, and licorisoflavan A possess potential beneficial effects in oral
      diseases. This paper reviews the effects of licorice and licorice constituents on
      both the oral microbial pathogens and the host immune response involved in common
      ora-dental diseases (dental caries, periodontitis, candidiasis, and recurrent
      aphthous ulcers). It also summarizes results of clinical trials that investigated
      the potential beneficial effects of licorice and its constituents for
      preventing/treating oro-dental diseases.

PMID- 21851509
TI  - Molecular findings in oral premalignant fields: update on their diagnostic and
      clinical implications.
AB  - The development of multiple oral tumours, seen in up to 30% of patients with a
      primary oral squamous cell carcinoma, is sometimes attributable to the presence
      of genetically altered premalignant fields and has important prognostic
      implications. Molecular techniques available for the definitive diagnosis of such
      a field (loss of heterozygosity analysis of 3p, 9p and 17p and study of TP53
      tumour suppressor gene mutation) are expensive, complex and not universally
      available, hampering their routine application. Nevertheless, molecular diagnosis
      is essential for modern assessment of the risk of multiple tumours and for
      decisions on the appropriate preventive and therapeutic approaches. This article
      reviews current knowledge on molecular findings in premalignant fields in the
      oral cavity and oropharynx and provides an update on criteria for their
      identification, discussing the clinical and therapeutic implications.

PMID- 21851510
TI  - Medical humanities' challenge to medicine.
AB  - Medicine is predicated on a view of human nature that is highly positivist and
      atomistic. This is apparent in the way in which its students are taught, clinical
      consultations are structured and medical evidence is generated. The field of
      medical humanities originally emerged as a challenge to this overly narrow view,
      but it has rarely progressed beyond tinkering around the edges of medical
      education. This is partly because its practitioners have largely been working
      from within a pervasive medical culture from which it is difficult to break free,
      and partly because the field has been insufficiently armed with scholarly
      thinking from the humanities. This is beginning to change and there is a sign
      that research in medical humanities has the potential to mount a persuasive
      challenge to medicine's ways of teaching, working and finding out. This article
      problematizes medicine's narrow viewpoint, grounding its critique in
      philosophical ideas from phenomenology and pragmatism. I will reflect upon the
      historical context within which medical humanities has emerged and briefly
      examine specific examples of how its interdisciplinary approach, involving
      humanities scholars with clinicians and medical scientists, may develop new
      research directions in medicine.

PMID- 21851511
TI  - Improved health or improved decision making? The ethical goals of EBM.
AB  - Evidence-based medicine (EBM) is frequently portrayed as a value-free approach to
      knowing what kinds of treatment 'really work.' Since practitioners should help
      patients to improve their health, and EBM tells us which interventions will work,
      then it follows that we must practice EBM, offering only those interventions
      supported by evidence. The primary goal of EBM, then, is an ethical one - to
      improve health. More recently, EBM's authors have also committed themselves to
      'shared decision making' in which evidence plays a role in the clinical
      encounter, but where patients, motivated by their own values, should have final
      decision-making authority. Envisioned this way, strengthening the informed
      consent process, rather than improved health per se, is viewed as the goal of
      EBM. In this paper, I will explore this shift in EBM's ethics from the goal of
      improved health towards the goal of strengthened informed consent. Drawing upon
      data from a qualitative enquiry of scholars involved in the development of EBM, I
      will argue that EBM is now committed to both of these ethical goals. Where they
      conflict, the aim of the intervention will determine which goal practitioners
      should pursue. Having increased the ethical complexity of EBM, we are left with
      the question of whether EBM would still be judged a success if it did not lead to
      much in the way of improvements in health, but primarily strengthened informed
      consent. This paper will conclude by arguing that this more nuanced version of
      EBM's ethics accurately reflects the dynamics of real clinical practice but
      undermines the original, perceived need for EBM.

PMID- 21851512
TI  - Validity and reliability study on traditional Chinese FACT-C in Chinese patients
      with colorectal neoplasm.
AB  - OBJECTIVE: To establish the validity and reliability of traditional Chinese
      version of the Functional Assessment of Cancer Therapy-Colorectal (FACT-C).
      METHODS: A total of 536 subjects self-administered (n = 331) or interviewer
      administered (n = 205) FACT-C (version 4), EORTC QLQ-C30/CR38 and SF-12v2
      instruments for health-related quality of life assessment. Construct validity was
      examined by item-scale correlation, scaling success and concurrent validity.
      Reliability was evaluated by test-retest reliability and internal consistency.
      Sensitivity was assessed by known-groups comparisons. RESULTS: The completion
      rates for FACT-C were almost perfect (>98%). The FACT-C demonstrated item
      internal consistency and item discriminant validity through item-scale
      correlation. Scaling success and concurrent validity were satisfactory to support
      the construct validity. The five subscales of the FACT-C showed good internal
      consistency with Cronbach alpha coefficient and substantial reproducibility,
      demonstrating good reliability. Sensitivity was supported when there were
      significant differences in scores related to physical condition between patients
      who were receiving treatment and those who were not. CONCLUSION: Traditional
      Chinese version of the FACT-C was demonstrated to have satisfactory psychometric
      properties in terms of applicability, reliability, validity and sensitivity in
      Chinese patients with colorectal neoplasm. The FACT-C was valid colorectal
      specific health-related quality of life tool for the Chinese population.

PMID- 21851513
TI  - Cloning and characterization of alpha-L-arabinofuranosidase and bifunctional
      alpha-L-arabinopyranosidase/beta-D-galactopyranosidase from Bifidobacterium
      longum H-1.
AB  - AIMS: This study focused on the cloning, expression and characterization of
      recombinant alpha-l-arabinosidases from Bifidobacterium longum H-1. METHODS AND
      RESULTS: alpha-l-Arabinofuranosidase (AfuB-H1) and bifunctional alpha-l
      arabinopyranosidase/beta-d-galactosidase (Apy-H1) from B. longum H-1 were
      identified by Southern blotting, and their recombinant enzymes were overexpressed
      in Escherichia coli BL21 (DE3). Recombinant AfuB-H1 (rAfuB-H1) was purified by
      single-step Ni(2+) -affinity column chromatography, whereas recombinant Apy-H1
      (rApy-H1) was purified by serial Q-HP and Ni(2+) -affinity column chromatography.
      Enzymatic properties and substrate specificities of the two enzymes were
      assessed, and their kinetic constants were calculated. According to the results,
      rAfuB-H1 hydrolysed p-nitrophenyl-alpha-l-arabinofuranoside (pNP-alphaL-Af) and
      ginsenoside Rc, but did not hydrolyse p-nitrophenyl-alpha-l-arabinopyranoside
      (pNP-alphaL-Ap). On the other hand, rApy-H1 hydrolysed pNP-alphaL-Ap, p
      nitrophenyl-beta-d-galactopyranoside (pNP-betaD-Ga) and ginsenoside Rb2.
      CONCLUSIONS: Ginsenoside-metabolizing bifidobacterial rAfuB-H1 and rApy-H1 were
      successfully cloned, expressed, and characterized. rAfuB-H1 specifically
      recognized the alpha-l-arabinofuranoside, whereas rApy-H1 had dual functions,
      that is, it could hydrolyse both beta-d-galactopyranoside and alpha-l
      arabinopyranoside. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest
      that the biochemical properties and substrate specificities of these recombinant
      enzymes differ from those of previously identified alpha-l-arabinosidases from
      Bifidobacterium breve K-110 and Clostridium cellulovorans.

PMID- 21851514
TI  - Statins in non-ischaemic cardiomyopathy: an update on our current clinical and
      pathophysiological understanding.
AB  - Statins are a cornerstone in reducing cardiovascular events. Studies show that
      statins are beneficial even in patients with normal or low cholesterol levels,
      indicating pleiotropic mechanisms of therapeutic benefit apart from their
      antihyperlipidemic effect. Non-randomised, observational and retrospective
      studies suggest that statins are associated with better outcomes in patients with
      heart failure (HF) of both ischaemic and non-ischaemic aetiologies. While
      cholesterol reduction and plaque stabilisation likely play a role in reducing
      cardiovascular events in ischaemic HF patients, the mechanisms underlying the
      benefit in non-ischaemic HF patients is less clear. This review suggests the
      pleiotropic effects of statin therapy can beneficially alter the
      pathophysiological mechanisms underlying the clinical benefit observed in non
      ischaemic HF patients.

PMID- 21851517
TI  - British HIV Association and British Infection Association guidelines for the
      treatment of opportunistic infection in HIV-seropositive individuals 2011.

PMID- 21851516
TI  - Optimizing weight gain in pregnancy to prevent obesity in women and children.
AB  - Pregnancy is now considered to be an important risk factor for new or persistent
      obesity among women during the childbearing years. High gestational weight gain
      is the strongest predictor of maternal overweight or obesity following pregnancy.
      A growing body of evidence also suggests that both high and low gestational
      weight gains are independently associated with an increased risk of childhood
      obesity, suggesting that influences occurring very early in life are contributing
      to obesity onset. In response to these data, the US Institute of Medicine (IOM)
      revised gestational weight gain guidelines in 2009 for the first time in nearly
      two decades. However, less than one third of pregnant women achieve guideline
      recommended gains, with the majority gaining above IOM recommended levels. To
      date, interventions to optimize pregnancy weight gains have had mixed success. In
      this paper, we summarize the evidence from human and animal studies linking over
      nutrition and under-nutrition in pregnancy to maternal and child obesity. In
      addition, we discuss published trials and ongoing interventions to achieve
      appropriate gestational weight gain as a strategy for obesity prevention in women
      and their children.

PMID- 21851532
TI  - Outcomes of long-term follow-up of patients with conservative management of
      asymptomatic renal calculi.
AB  - OBJECTIVE: * To evaluate the long-term outcomes of patients undergoing
      observation of asymptomatic renal calculi. PATIENTS AND METHODS: * This is a
      retrospective review of 50 patients with 85 stones undergoing observation with
      annual imaging from January 2005 to December 2009. * The incidences of
      spontaneous stone passage, stone progression and intervention were evaluated and
      assessed for statistical difference according to initial size and location of
      stone. * Percutaneous nephrolithotomy, shock wave lithotripsy and ureteroscopy
      were performed when patients developed complications from the stones. RESULTS: *
      Patients were followed up for a mean of 46 months. Sixteen percent had bilateral
      stones and 38% had multiple stones. * The average stone size was 5.7 mm and 31%,
      26% and 43% of the stones were located in the upper, middle and lower pole
      respectively. * Overall incidences of spontaneous passage, progression and
      intervention were 20%, 45.9% and 7.1% respectively. * Stones measuring 5 mm or
      less were significantly more likely to pass (P= 0.006). * There was no
      significant difference in the incidence of passage according to the initial
      location of the stone (P= 0.092). There was no significant difference in
      intervention or progression according to the initial size (P= 0.477 and 0.282
      respectively) or location of stone (P= 0.068 and 0.787 respectively).
      CONCLUSIONS: * Patients with asymptomatic renal stones may be managed
      conservatively in view of low risk of intervention (7.1%). * Annual imaging
      should be performed as half of these stones will progress in size.

PMID- 21851533
TI  - Tumour diameter and decreased preoperative estimated glomerular filtration rate
      are independently correlated in patients with renal cell carcinoma.
AB  - OBJECTIVE: To examine the relationship between tumour diameter and estimated GFR
      (eGFR) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In
      total, 1009 patients undergoing partial or radical nephrectomy for unilateral RCC
      were identified in the Columbia Urologic Database. eGFR was calculated using the
      modification of diet in renal disease equation using demographic data and
      preoperative serum creatinine values. Data on patient demographics, tumour
      characteristics, and comorbidities were analyzed using univariate and
      multivariate regression analysis. RESULTS: Mean (sd, range) tumour diameter was
      5.29 (3.8, 0.3-29) cm. Mean (sd, range) eGFR was 75 (23.4, 3-173) mL/min per 1.73
      m(2) . In multivariate regression analysis, tumour diameter independently
      predicted decreased preoperative eGFR (coefficient, -0.513; P= 0.008) when
      controlling for hypertension and race. Consistent with this, decreased
      preoperative eGFR independently predicted increased tumour diameter (coefficient,
      -0.013; P= 0.007) when controlling for race, histology and smoking status.
      CONCLUSION: Tumour diameter and decreased preoperative eGFR are independently
      correlated in patients with RCC.

PMID- 21851534
TI  - Seminal vesicle invasion: what is the best adjuvant treatment after radical
      prostatectomy?
AB  - OBJECTIVE: * To evaluate the biochemical-failure free survival according to
      different adjuvant treatments in patients who underwent radical prostatectomy
      (RP) with seminal vesicle invasion (SVI). PATIENTS AND METHODS: * Between 1994
      and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. *
      Exclusion criteria were: detectable postoperative prostate-specific antigen,
      lymph node metastases and follow-up <18 months. * Therefore, the study group
      included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26
      received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant
      ADT combined with RT and 82 were monitored. The endpoint for this analysis was
      biochemical no evidence of disease (bNED). * Preoperative prostate-specific
      antigen level, specimen Gleason score, age, clinical stage, surgical margin
      status and adjuvant treatment were evaluated in a multivariable analysis with
      respect to bNED survival. RESULTS: * After a mean (range) follow-up of 60.3 (18
      185) months, 88 (44.2%) patients had a biochemical relapse. * The estimated 5-
      and 7-year bNED survival were 32.6% and 25.9% for the observation group, 44.4%
      and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8%
      and 62.1% for the adjuvant ADT combined with RT group. * On multivariate
      analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent
      prognostic factor of biochemical relapse. CONCLUSIONS: * RP appeared to be
      insufficient as a single treatment for patients with SVI. * The findings of the
      present study suggest that adjuvant ADT combined with RT after RP for patients
      with SVI confers a substantial benefit on 5-year bNED survival.

PMID- 21851535
TI  - Serum testosterone level as a predictor of biochemical failure after radical
      prostatectomy for localized prostate cancer.
AB  - OBJECTIVE: * To investigate serum testosterone levels as a predictor for
      biochemical failure (BF) after radical retropubic prostatectomy (RRP). PATIENTS
      AND METHODS: * Prospective cohort study with 227 patients and a median follow-up
      of 7.7 years. * Total serum testosterone was measured at diagnosis. * Primary
      endpoint: 5-year BF-free survival defined as first PSA > 0.2 ng/mL. *
      Testosterone was tested as a predictor of BF as a dichotomized and continuous
      variable. RESULTS: * Median (range) age was 62 years (45-74), median PSA 9.9
      ng/mL (0.4-96), and median testosterone was 14 nmol/L (2.2-40). * BF occurred for
      57 patients (26%) within 5 years. * In multivariate analysis with age, PSA, and
      biopsy Gleason score, testosterone levels >11 nmol/L were an independent
      predictor for reduced risk of BF (hazard ratio, 0.53; 95% confidence interval,
      0.31-0.90; P= 0.02). * When analyzed as a continuous variable, testosterone was
      not a statistically significant predictor of BF. CONCLUSION: * Low pretreatment
      serum testosterone levels correlate with a higher risk of BF, and testosterone
      may possess biological information about prostate cancer progression potential,
      which makes it an independent predictor of biochemical failure after RRP.

PMID- 21851536
TI  - Analysis of regional lymph nodes in periprostatic fat following robot-assisted
      radical prostatectomy.
AB  - OBJECTIVE: * To determine the incidence and significance of lymph nodes in the
      anterior prostatovesicular lymphofatty tissue. PATIENTS AND METHODS: * One
      hundred and twenty patients with clinically localized prostate cancer underwent
      robot-assisted laparoscopic radical prostatectomy with excision of anterior
      prostatovesicular tissue at a single institution over a 6-month period. * Tissue
      was sent for pathological analysis. * Separate pelvic lymph node dissection was
      carried out in moderate-risk and high-risk patients. RESULTS: * A total of 20 out
      of 120 patients (16.7%) had lymph nodes in the anterior lymphofatty tissue. *
      Average lymph node number when present was 1.5 (one to three). * Pathological
      assessment of the lymph nodes revealed metastatic prostate cancer in 3 out of 120
      (2.5%) patients, each of whom had adverse pathological features. * Patients with
      metastatic lymph nodes in the anterior tissue did not have cancer involvement of
      the pelvic lymph nodes. * Patients with lymph nodes found in the anterior
      lymphofatty tissue were slightly younger but were otherwise similar with respect
      to other demographics, prostate-specific antigen, biopsy Gleason score, clinical
      stage, pathological stage, pathological Gleason score, seminal vesicle invasion,
      and margin status. CONCLUSIONS: * Anterior lymphofatty tissue overlying the
      prostate occasionally contains lymph nodes that can harbour malignant disease and
      routine excision may eradicate regional tumour burden. * Of patients with nodes,
      15% were found to have malignant involvement. * The long-term impact on
      progression-free and overall survival requires further study.

PMID- 21851537
TI  - Development of male genital lichen sclerosus in penile reconstruction skin grafts
      after cancer surgery: an unreported complication.
AB  - OBJECTIVE: * To describe the incidence of the development of male genital lichen
      sclerosus (LS) in non-genital skin grafts used in penile reconstruction after
      cancer surgery. PATIENTS AND METHODS: * Between 1997 and 2009, 177 patients
      received surgical treatment for penile cancer in the Urology Department at
      Sunderland Royal Hospital, the regional penile cancer centre for the north-east
      of England. * Patients who had organ-sparing surgery and non-genital penile graft
      reconstructions were identified. * Histology reports for specimens obtained from
      those grafts were reviewed to identify the presence of male genital LS and the
      incidence of recurrence of squamous cell carcinoma (SCC). RESULTS: * The mean
      (range) age of patients at diagnosis was 61.8 (32-89) years. Of the 177 patients,
      139 had SCC, 32 had carcinoma in situ and six had verrucous carcinoma. * In
      total, 56 penile reconstructive procedures were performed using split-thickness
      skin grafts obtained from the inner thigh. * From those grafts, 18 specimens were
      obtained later for cosmetic, diagnostic or curative purposes. * Male genital LS
      was found in six of the 18 specimens, and one of them was associated with
      recurrent verrucous carcinoma. CONCLUSIONS: * This is the first published series
      to describe the incidence of male genital LS in penile skin grafts taken from a
      remote site after penile cancer surgery. * These results represent new
      information that might help explain the aetiology of male genital LS.

PMID- 21851538
TI  - Evaluation of different lymph node (LN) variables as prognostic markers in
      patients undergoing radical cystectomy and extended LN dissection to the level of
      the inferior mesenteric artery.
AB  - OBJECTIVE: To evaluate the prognostic impact of lymph node (LN) variables in
      patients undergoing radical cystectomy (RC) and extended LN dissection. PATIENTS
      AND METHODS: From January 2004 to January 2009, 167 patients with bladder cancer
      underwent RC and extended LN dissection to the level of the inferior mesenteric
      artery in a surgery-only series with no neoadjuvant or adjuvant chemotherapy.
      Correlation to prognosis of different LN variables according to presence of LN
      metastasis, number, localization, extracapsular extension (ECE), size, volume, LN
      density and N-stage according to two different Tumour-Node-Metastasis (TNM)
      classifications were analysed. RESULTS: In all, 43 patients (26%) had LN
      metastases. In univariate analysis, gender, T-stage and several different LN
      variables stratified by presence of LN metastasis, number of positive LNs,
      anatomical localisation, ECE, LN density, size and volume of positive LNs, were
      significant prognostic predictors. Female gender, advanced T-stage, presence of
      LN metastasis, non-regional LN metastases (M-positive) and number of positive LNs
      (1 vs >1) were significant adverse prognostic predictors in multivariate
      analysis, whereas the other LN variables were not. Inclusion of the common iliac
      LNs in the regional LNs as suggested in the seventh edition of the TNM
      classification was relevant regarding prognosis. However, subclassification based
      on location was not correlated to prognosis. The new N3 category therefore seems
      superfluous. CONCLUSIONS: LN-positive patients have a poor prognosis, especially
      if >1 positive LN is present. Despite several different suggestions of new LN
      dependent prognostic factors, none of the tested variables were independently
      significant in the present series.

PMID- 21851539
TI  - Long-term efficacy and tolerability of once-yearly histrelin acetate subcutaneous
      implant in patients with advanced prostate cancer.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of a once-yearly histrelin
      implant during an open-label extension of a pivotal study. PATIENTS AND METHODS:
      Men with advanced prostate cancer and a clinical response to 52 weeks of
      treatment with the histrelin implant. Implants were placed annually. The primary
      efficacy variable was achievement of serum testosterone levels of <=50 ng/dL.
      Secondary efficacy variables were disease progression, analgesia use, performance
      status and tolerability of therapy. RESULTS: Of 104 patients enrolled, over 70%
      received three consecutive histrelin implants, and the longest, single treatment
      period was greater than 4 years. Serum testosterone was consistently suppressed
      below 50 ng/dL in all patients and mean testosterone levels were 13.1, 14.8 and
      10.8 ng/dL after 104 weeks (year 2), 156 weeks (year 3) and 208 weeks (year 4) of
      treatment, respectively. Most patients showed no clinical worsening of their
      disease, were able to continue normal daily activities, and did not require
      analgesic medication during the extension period. Mean (SD) time to place the
      histrelin implant was 4.5 (6.2) min, with only three patients having insertions
      that were considered difficult. Adverse events were reported in 100 (96.2%)
      patients. The eight deaths and 28 (26.9%) serious adverse events were judged as
      unrelated to the study drug. The most commonly reported drug-related adverse
      events was hot flashes in 67 (64.4%) patients. Most of these cases was judged as
      mild or moderate. CONCLUSIONS: The once-yearly histrelin implant maintained
      testosterone suppression for repeated treatment cycles and was generally well
      tolerated. The histrelin implant provides a clinically attractive option for long
      term androgen deprivation therapy in patients with advanced prostate cancer
      seeking fewer office visits and repeated injections.

PMID- 21851540
TI  - Sex differences in bladder cancer outcomes among smokers with advanced bladder
      cancer.
AB  - OBJECTIVE: To study the effect of smoking on bladder cancer presentation and
      outcome in a large cystectomy population. PATIENTS AND METHODS: A database
      including 546 patients from the University Health Network (Toronto, Canada) and
      Turku University Hospital (Turku, Finland) was studied. In addition to the
      association of smoking with clinicopathological parameters, the effect of smoking
      on survival was analyzed. Categorical data were analyzed by the chi-squared test
      and numerical data were analyzed by Student's t-test. The Kaplan-Meier method,
      log-rank test and a proportional hazards model were used to estimate the effect
      of smoking on survival. RESULTS: In total, 352 patients (64%) were smokers and
      194 (36%) were non-smokers. Smokers had more frequently advanced tumours and
      nodal metastasis. The 10-year disease-specific survival (DSS) was 52% vs 66% for
      smokers and non-smokers, respectively (P = 0.039). Smokers also had significantly
      worse overall survival (10-year overall survival 37% vs 62%; P = 0.015). Smoking
      affected significant DSS among men (P = 0.012), although no effect was observed
      among women. In a univariate model smoking was associated with a hazard ratio
      (HR) of 1.4 (95% confidence interval, CI, 1.0-1.9) for bladder cancer specific
      mortality and 1.4 (95% CI, 1.1-1.8) for overall mortality. In a multivariate
      model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8-1.6; P = 0.41). In
      addition to advanced stage and nodal metastasis, female sex was an independent
      risk factor for DSS (HR, 1.6; 95% CI, 1.1-2.3; P = 0.007). CONCLUSIONS: Smokers
      appear to have worse outcomes after radical cystectomy for bladder cancer;
      however, it does not appear to be an independent prognostic factor for survival.
      Smoking affected survival only among men. Women had poorer survival but smoking
      was not a contributing factor to this.

PMID- 21851541
TI  - Renoprotective effect of pulsatile perfusion machine RM3: pathophysiological and
      kidney injury biomarker characterization in a preclinical model of
      autotransplanted pig.
AB  - OBJECTIVES: To assess the effect of machine perfusion (MP) on renal function
      recovery vs kidney preservation in static cold storage (CS), in a large animal
      preclinical model. To assess whether MP benefits are dependent on the
      preservation solution used. METHODS: Using an established autotransplantation pig
      kidney model associated with a contralateral nephrectomy we studied the impact of
      MP against the deleterious effects of warm ischaemia (WI; 60 min), then 22 h of
      cold ischaemia using MP or static CS, followed by autotransplantation. We used
      Berzer MP solution (MPS), recommended for MP, and Institut Georges Lopez
      preservation solution (IGL-1), designed for CS. The pigs were divided into four
      study groups: MPS-CS: static CS with MPS (n = 7); MPS-MP: renal perfusion with
      MPS using the Waters Medical Systems (Rochester, MN, USA) RM3 pulsatile machine
      (n = 7); IGL-CS: static CS with IGL-1 solution (n = 7); IGL-MP: renal perfusion
      with IGL-1 solution (n = 7). The effect of ischaemia was determined using
      different variables: pig survival; plasma creatinine; proteinuria; oxidative
      stress; tubular sodium reabsorption rate; and tissue damage at 1 month. RESULTS:
      Pig survival was higher in MP and IGL groups compared to MPS-CS. Plasma
      creatinine levels did not differ among the groups, but proteinuria assay showed
      significant benefits for the MP vs static CS groups. Histological evaluation of
      kidney grafts showed more injury in the CS groups than in the MP groups. Urinary
      measurement of tubular enzyme activity differed substantially among the groups,
      highlighting the benefits of MP in maintaining brush border integrity.
      CONCLUSIONS: In our model reproducing the conditions of deceased after cardiac
      arrest donors we show that MP decreases the risk of renal dysfunction and
      preserves kidney parenchyma. A non-invasive urinary enzyme assay can provide
      valuable information on graft integrity. The preservation solution used is
      important as the wrong solution can decrease the benefits of MP.

PMID- 21851543
TI  - Modified technique of robotic-assisted simple prostatectomy: advantages of a
      vesico-urethral anastomosis.
AB  - OBJECTIVES: To describe a technical modification during robotic-assisted simple
      prostatectomy (RASP) aiming to decrease perioperative blood loss, shorten the
      length of hospital stay and eliminate the need of postoperative continuous
      bladder irrigation. To describe perioperative outcomes, pathological findings and
      functional outcomes of our single-surgeon series using this technique. METHODS:
      We analysed six consecutive patients who underwent RASP using our technical
      modification between February and September 2010. Transrectal ultrasonography
      (TRUS) guided prostate biopsy was performed in all cases and revealed benign
      prostatic hyperplasia in two cases and benign prostatic hyperplasia plus chronic
      prostatitis in four cases. The mean estimated prostate volume in the TRUS was 157
      +/- 74 (range 90-300) mL and the average preoperative International Prostate
      Symptom score was 19.8 +/- 9.6 (10-32). Two patients were in urinary retention
      before surgery. Our technique of RASP includes the standard operative steps
      reported during open and laparoscopic simple prostatectomy; however, with the
      addition of some technical modifications during the reconstructive part of the
      procedure. Following the resection of the adenoma, instead of performing the
      classical 'trigonization' of the bladder neck and closure of the prostatic
      capsule, we propose three modified surgical steps: plication of the posterior
      prostatic capsule, a modified van Velthoven continuous vesico-urethral
      anastomosis and, finally, suture of the anterior prostatic capsule to the
      anterior bladder wall. RESULTS: The patients' average age was 69 +/- 4.9 (63-74)
      years; the mean estimated blood loss was 208 +/- 66 (100-300) mL and the mean
      operative time was 90 +/- 17.6 (75-120) min. All patients were discharged on
      postoperative day 1 without the need of continuous bladder irrigation at any time
      after RASP. No blood transfusion or perioperative complications were reported.
      The mean weight of the surgical specimen was 145 +/- 41.6 (84-186) g.
      Histopathological evaluation revealed benign prostatic hyperplasia plus chronic
      prostatitis in five patients and prostatic adenocarcinoma (Gleason score 3+3,
      pT1a) with negative surgical margins in one patient. The mean serum prostate
      specific antigen level decreased from 7 +/- 2.5 (4.2-11) ng/mL preoperatively to
      1.05 +/- 0.8 (0.2-2.5) after RASP. Significant improvement from baseline was
      reported in the average International Prostate Symptom score (average
      preoperative vs postoperative, 19.8 +/- 9.6 vs 5.5 +/- 2.5, P= 0.01) and in mean
      maximum urine flow (average preoperative vs postoperative 7.75 +/- 3.3 vs 19 +/-
      4.5 mL/s, P= 0.019) at 2 months after RASP. All patients were continent (defined
      as the use of no pads) at 2 months after RASP. CONCLUSIONS: Our modified
      technique of RASP is a safe and feasible option for treatment of lower urinary
      tract symptoms caused by large prostatic adenomas. Potential advantages of our
      technique include reduced blood loss, lower blood transfusion rates and shorter
      length of hospital stay with no need of postoperative continuous bladder
      irrigation. Larger series with longer follow-up are necessary to determine long
      term outcomes in comparison to open simple prostatectomy or to the standard
      technique of RASP.

PMID- 21851542
TI  - Amelioration of diabetes-induced cavernosal fibrosis by antioxidant and anti
      transforming growth factor-beta1 therapies in inducible nitric oxide synthase
      deficient mice.
AB  - OBJECTIVE: *  To investigate whether sustained long-term separate treatments of
      diabetic inducible nitric oxide synthase knockout (iNOSKo) mice with allopurinol,
      an antioxidant inhibiting xanthine oxidoreductase, decorin, a transforming growth
      factor-beta1 (TGFbeta1) -binding antagonist, and molsidomine, a long-life nitric
      oxide donor, prevent the processes of diabetes-induced cavernosal fibrosis.
      MATERIALS AND METHODS: *  Eight week old male iNOS knock out (iNOSKo) mice were
      made diabetic by injecting 150 mg/kg B.W Streptozotocin (1P) with were either
      left untreated or treated with the oral antioxidant allopurinol (40 mg/kg/day),
      or decoin (50 mg, 1P, twice), as an anti-TGFbeta1 agent (n = 8/group). * 
      Glycemia and oxidative stress markers were determined in blood and urine. * 
      Paraffin-embedded tissue sections from the penile shaft were subjected to Masson
      trichrome staining for the smooth muscle (smc)/collagen ratio, and imunostaining
      for smc content, profibrotic factors, oxidative stress, cell replication and cell
      death markers followed by quantitative image analysis. RESULTS: *  Eight-week
      treatment with either allopurinol or decorin counteracted the decrease in smooth
      muscle cells and the increase in apoptosis and local oxidative stress within the
      corpora tissue. *  Decorin but not allopurinol increased the smooth muscle
      cell/collagen ratio, whereas allopurinol but not decorin inhibited systemic
      oxidative stress. *  Molsidomine was effective in reducing both local and
      systemic oxidative stress, but did not prevent corporal fibrosis. CONCLUSION: * 
      Both allopurinol and decorin appear as promising approaches either as a single or
      a combined pharmacological modality for protecting the diabetic corpora from
      undergoing apoptosis and fibrosis although their functional effects still need to
      be defined.

PMID- 21851544
TI  - Nerve sparing can preserve orgasmic function in most men after robotic-assisted
      laparoscopic radical prostatectomy.
AB  - OBJECTIVE: *  To investigate orgasmic outcomes in patients undergoing robotic
      assisted laparoscopic radical prostatectomy (RALP) and the effects of age and
      nerve sparing on these outcomes. PATIENTS AND METHODS: *  Between January 2005
      and June 2007, 708 patients underwent RALP at our institution. *  We analysed
      postoperative potency and orgasmic outcomes in the 408 men, of the 708, who were
      potent, able to achieve orgasm preoperatively and available for follow-up.
      RESULTS: *  Of men aged <=60 years, 88.4% (198/224) were able to achieve orgasm
      postoperatively in comparison to 82.6% (152/184) of older men (P < 0.001). *  Of
      patients who received bilateral nerve sparing (BNS) during surgery, 273/301
      (90.7%) were able to achieve orgasm postoperatively compared with 46/56 (82.1%)
      patients who received unilateral nerve sparing and 31/51 (60.8%) men who received
      non-nerve-sparing surgery (P < 0.001). *  In men <=60 years who also underwent
      BNS, decreased sensation of orgasm was present in 3.2% of men, and postoperative
      orgasmic rates were significantly better than men <=60 years who underwent
      unilateral or no nerve sparing (92.9% vs 83.3% vs 65.4%, respectively; P <
      0.001). *  Potency rates were also significantly higher in men <=60 years and in
      those who underwent BNS. CONCLUSIONS: *  Age and nerve sparing influence recovery
      of orgasm and erectile function after RALP. *  Men <=60 years old and those who
      undergo BNS are most likely to maintain normal sexual function.

PMID- 21851545
TI  - Measuring erectile function after radical prostatectomy: comparing a single
      question with the International Index of Erectile Function.
AB  - OBJECTIVE: To present a single-question institutional erectile function scale,
      which was developed at Memorial Sloan-Kettering Cancer Center (MSKCC) before the
      availability of the International Index of Erectile Function (IIEF), and to
      compare its performance with the IIEF. Erectile function status assessment after
      radical prostatectomy is a significant challenge both for research purposes and
      in clinical practice. Recently, there has been a shift away from complex
      questionnaire use such as the IIEF and regression to single-item assessment of
      erectile function. PATIENTS AND METHODS: Our erectile function score, a single
      question 5-point score based on physician-patient interview, was applied to 276
      patients with prostate cancer after radical prostatectomy. Based on the erectile
      function score, patients were grouped into five groups. The mean IIEF score and
      the mean score of questions 3 and 4 of the IIEF were calculated and compared
      across the groups. Each score group was compared with the preceding group and
      tested for significant difference. The erectile function domain of the IIEF and
      the institutional score were tested for correlation. RESULTS: The complete
      erectile function domain score from the IIEF was available for 170 patients and
      scores from questions 3 and 4 were available for 220 patients. The institutional
      erectile function score categorized the subjects into distinct groups based on
      erectile function status. The institutional erectile function score was highly
      correlated with the IIEF erectile function domain score (r=-0.692, P < 0.001) and
      with the questions 3 and 4 combined score (r=-0.678, P < 0.001). CONCLUSIONS: The
      MSKCC erectile function scale is a practical, readily administered method to
      assess erectile function in patients with prostate cancer after radical
      prostatectomy. The erectile function score, as determined by this scale, is
      highly correlated with the IIEF erectile function domain score.

PMID- 21851547
TI  - Expression of the tumour antigen T21 is up-regulated in prostate cancer and is
      associated with tumour stage.
AB  - OBJECTIVES: * To define the expression pattern of the tumour antigen T21 at the
      protein level in prostate tissues, prostate cell lines and a panel of normal
      tissues. * To correlate the expression pattern of T21 in prostate cancer with
      clinical parameters. PATIENTS AND METHODS: * Tissue samples were collected from
      79 patients presenting at clinic with either prostate cancer (63 patients) or
      benign prostatic hyperplasia (BPH, 16 patients). * A tissue microarray (TMA) was
      constructed from 44 of the prostate cancer tissues and areas of benign disease
      (43 patients) from these tissues were also included on the TMA. The remaining
      tissues (prostate cancer 19 patients and BPH 16 patients) were mounted fresh
      frozen onto cork boards and sectioned. * Full ethical approval was granted for
      all aspects of the study and informed patient consent was taken before tissue
      collection. * Immunohistochemistry was used on the prostate tumour TMA, the
      normal tissue TMA and the fresh-frozen prostate tissues. Fluorescent microscopy
      and flow cytometry was performed on prostate cell lines. RESULTS: * Expression of
      T21 was highly restricted within normal tissues with only the stomach, ovary,
      breast and prostate having detectable T21 expression. * T21 was significantly
      over-expressed in prostate cancer glands compared with benign tissue and was
      present in >80% of the malignant specimens analysed. * Increased expression was
      positively correlated to pathological stage of prostate tumours. * Additionally,
      T21 was associated with Gleason grade and prostate-specific antigen recurrence,
      although statistical significance was not reached in this restricted cohort of
      patients. CONCLUSION: * Taken together these results show that T21 is a potential
      new biomarker for advanced disease and that elevated levels of T21 appear
      relevant to prostate cancer development.

PMID- 21851548
TI  - Inhibition of bladder overactivity by stimulation of feline pudendal nerve using
      transdermal amplitude-modulated signal (TAMS).
AB  - OBJECTIVE: * To develop a non-invasive neuromodulation method targeting the
      pudendal nerve. MATERIALS AND METHODS: * Bladder overactivity induced by acetic
      acid (AA) irritation was partially suppressed by electrical stimulation of the
      pudendal nerve in alpha-chloralose anaesthetized cats using a transdermal
      amplitude-modulated signal (TAMS). RESULTS: * During cystometrography (CMG),
      intravesical infusion of 0.25% AA significantly decreased the mean (se) bladder
      capacity to 28.8 (5.9)% of the capacity measured during saline infusion. * The
      TAMS stimulation inhibited AA-induced bladder overactivity at 5, 7 and 10 Hz, and
      significantly increased the mean (se) bladder capacity to 61.8 (9.9)%, 51.3
      (14.5)%, 53.6 (14.9)%, respectively, of the control capacity during saline
      infusion, whereas stimulation at 20-40 Hz had no effect. * Under isovolumetric
      conditions at a bladder volume ranging between 130 to 160% of the bladder
      capacity measured during AA infusion, TAMS stimulation at all frequencies (5-40
      Hz) significantly suppressed the irritation-induced rhythmic bladder
      contractions, reduced the area under the bladder pressure curve, and decreased
      the frequency of bladder contractions. However, the amplitude of rhythmic bladder
      contractions was only significantly decreased at stimulation frequencies of 5-20
      Hz. * At bladder volumes above the AA control capacity, TAMS stimulation with
      frequencies of 20-30 Hz had an excitatory effect, resulting in large amplitude
      (>25 cmH(2) O) bladder contractions. CONCLUSIONS: * TAMS stimulation targeting
      the cat pudendal nerve can inhibit C-fibre afferent-mediated bladder
      overactivity. * Thus, clinical research seems warranted to explore the usefulness
      of this technology for patients with overactive bladder symptoms.

PMID- 21851549
TI  - Long-term outcomes of augmentation ileocystoplasty in patients with spinal cord
      injury: a minimum of 10 years of follow-up.
AB  - OBJECTIVE: To report the long-term outcomes of augmentation ileocystoplasty (AIC)
      in patients with spinal cord injury (SCI), with a minimum follow-up period of 10
      years. PATIENTS AND METHODS: We retrospectively analysed all operations performed
      by a single surgeon at a specialist spinal unit. Outcomes were measured by
      comparing preoperative and follow-up videocystometrograms (VCMGs). Complications
      were identified from case notes and the surgery database. Subjective assessment
      was through a previously validated questionnaire. RESULTS: The mean (range)
      follow-up was 14.7 (10.5-20.3) years. There were 19 patients (12 males) with a
      mean (range) age at time of surgery of 28.9 (12-52) years. The mean (range)
      period from injury to surgery was 4.5 (0.3-22) years. All had suprasacral
      injuries. The VCMGs showed a significant improvement in bladder capacity and a
      decrease in intravesical pressures (P < 0.001). Long-term complications included
      bladder stones (n= 4); urosepsis (n= 2); vesico-ureteric reflux ([VUR]n= 2), VUR
      requiring ureteric re-implantation (n= 1); neurogenic detrusor overactivity
      ([NDO]n= 1); and laparatomy for bowel obstruction (n= 1). Surveillance
      cystoscopies did not detect any bladder neoplasms. The response rate for the
      questionnaire survey was 14/17; 13/14 patients were satisfied with the operation
      such that they would consider it again or recommend it to a friend. No patient
      reported any significant changes in either bowel habit or sexual function.
      CONCLUSIONS: We found that AIC has excellent long-term outcomes in the definitive
      management of refractory NDO in patients with SCI. The complications of AIC
      appear to be more than counterbalanced by a high level of patient satisfaction
      with the procedure and by the achievement of the primary aim of ensuring
      continence and upper tract safety in these patients.

PMID- 21851550
TI  - Decision curve analysis assessing the clinical benefit of NMP22 in the detection
      of bladder cancer: secondary analysis of a prospective trial.
AB  - OBJECTIVE: * To employ decision curve analysis to determine the impact of nuclear
      matrix protein 22 (NMP22) on clinical decision making in the detection of bladder
      cancer using data from a prospective trial. PATIENTS AND METHODS: * The study
      included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine
      cytology and measurement of urinary NMP22 levels. * We constructed several
      prediction models to estimate risk of bladder cancer. The base model was
      generated using patient characteristics (age, gender, race, smoking and
      haematuria); cytology and NMP22 were added to the base model to determine effects
      on predictive accuracy. * Clinical net benefit was calculated by summing the
      benefits and subtracting the harms and weighting these by the threshold
      probability at which a patient or clinician would opt for cystoscopy. RESULTS: *
      In all, 72 patients were found to have bladder cancer (5.5%). In univariate
      analyses, NMP22 was the strongest predictor of bladder cancer presence
      (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). * In
      multivariable prediction models, NMP22 improved the predictive accuracy of the
      base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus
      cytology by 4.2% (area under the curve 75.9-80.1%). * Decision curve analysis
      revealed that adding NMP22 to other models increased clinical benefit,
      particularly at higher threshold probabilities. CONCLUSIONS: * NMP22 is a strong,
      independent predictor of bladder cancer. * Addition of NMP22 improves the
      accuracy of standard predictors by a statistically and clinically significant
      margin. * Decision curve analysis suggests that integration of NMP22 into
      clinical decision making helps avoid unnecessary cystoscopies, with minimal
      increased risk of missing a cancer.

PMID- 21851551
TI  - Significance of histological prostatitis in patients with urinary retention and
      underlying benign prostatic hyperplasia or adenocarcinoma of the prostate.
AB  - OBJECTIVE: To compare the clinical features of patients having urinary retention
      and benign prostatic hyperplasia (BPH) with those having adenocarcinoma of the
      prostate (ACP) and to evaluate the significance of histological prostatitis.
      PATIENTS AND METHODS: The clinical data and histopathology reports of patients
      with retention admitted to Tygerberg Hospital between September 1998 and June
      2007 were evaluated. Statistical analysis was performed with Student's t-test,
      Mann-Whitney test and Fisher's exact test where appropriate and P < 0.05 was
      considered to indicate statistical significance. RESULTS: Prostatic histology was
      available in 405 patients, 204 with BPH and 201 with ACP. Comparing those with
      BPH and those with ACP showed statistically significant differences in mean age
      (69.5 vs 71.9 years), serum prostate-specific antigen (PSA) level (18.6 vs 899.5
      ng/mL) and histological prostatitis (48 vs 25%) but not duration of
      catheterization, prostate volume or urinary tract infection (UTI). Comparing
      those with BPH only and those with BPH plus prostatitis showed significant
      differences in mean age (71.9 vs 67.1 year) and PSA level (14.6 vs 22.8 ng/mL)
      but not prostate volume, UTI or duration of catheterization. Comparing those with
      ACP only and those with ACP plus prostatitis showed significant differences in
      stage T4 cancer (68.1 vs 35.4%) and PSA level (1123.4 vs 232.4 ng/mL) but not
      age, prostate volume, UTI or duration of catheterization. CONCLUSIONS:
      Histological prostatitis was almost twice as common in patients with urinary
      retention associated with underlying BPH than in patients with ACP, but there was
      no significant difference in the duration of catheterization, prostatic volume or
      presence of UTI, suggesting that histological prostatitis more often contributes
      to the development of retention in patients with underlying BPH than in those
      with ACP. In patients with BPH, histological prostatitis was associated with
      urinary retention at a significantly younger age and with higher serum PSA
      levels. In patients with ACP, histological prostatitis was associated with
      urinary retention at an earlier stage of cancer.

PMID- 21851552
TI  - Potato virus X movement in Nicotiana benthamiana: new details revealed by
      chimeric coat protein variants.
AB  - Potato virus X coat protein is necessary for both cell-to-cell and phloem
      transfer, but it has not been clarified definitively whether it is needed in both
      movement phases solely as a component of the assembled particles or also of
      differently structured ribonucleoprotein complexes. To clarify this issue, we
      studied the infection progression of a mutant carrying an N-terminal deletion of
      the coat protein, which was used to construct chimeric virus particles displaying
      peptides selectively affecting phloem transfer or cell-to-cell movement.
      Nicotiana benthamiana plants inoculated with expression vectors encoding the wild
      type, mutant and chimeric viral genomes were examined by microscopy techniques.
      These experiments showed that coat protein-peptide fusions promoting cell-to-cell
      transfer only were not competent for virion assembly, whereas long-distance
      movement was possible only for coat proteins compatible with virus particle
      formation. Moreover, the ability of the assembled PVX to enter and persist into
      developing xylem elements was revealed here for the first time.

PMID- 21851553
TI  - Medical devices in dermatology: topical semi-solid formulations for the treatment
      of skin diseases.
AB  - In recent years, topically applied semi-solid formulations certified as medicals
      devices and not as topical drugs are increasingly used for the treatment of skin
      diseases. Medical devices primarily unfold their therapeutic effect by physical
      means, not by pharmacological, immunological or metabolic means. Intensified
      placing of medical devices on the dermatological market may at least partly be
      explained by a less complex marketing authorization process compared to topical
      drugs. If the requirements are fulfilled to certify a product as a medical device
      the opportunity will be offered to quickly introduce innovations onto the market
      and propagate them. A variety of evidence-based medical devices for several
      dermatological indications are presented here.

PMID- 21851554
TI  - Extensive post-translational processing of potato tuber storage proteins and
      vacuolar targeting.
AB  - Potato tuber storage proteins were obtained from vacuoles isolated from field
      grown starch potato tubers cv. Kuras. Vacuole sap proteins fractionated by gel
      filtration were studied by mass spectrometric analyses of trypsin and
      chymotrypsin digestions. The tuber vacuole appears to be a typical protein
      storage vacuole absent of proteolytic and glycolytic enzymes. The major soluble
      storage proteins included 28 Kunitz protease inhibitors, nine protease inhibitors
      1, eight protease inhibitors 2, two carboxypeptidase inhibitors, eight patatins
      and five lipoxygenases (lox), which all showed cultivar-specific sequence
      variations. These proteins, except for lox, have typical endoplasmic reticulum
      (ER) signal peptides and putative vacuolar sorting determinants of either the
      sequence or structure specific type or the C-terminal type, or both.
      Unexpectedly, sap protein variants imported via the ER showed multiple molecular
      forms because of extensive and unspecific proteolytic cleavage of exposed N- and
      C-terminal propeptides and surface loops, in spite of the abundance of protease
      inhibitors. Some propeptides are potential novel vacuolar targeting peptides. In
      the insoluble vacuole fraction two variants of phytepsin (aspartate protease)
      were identified. These are most probably the processing enzymes of potato tuber
      vacuolar proteins. Database Proteome data have been submitted to the PRIDE
      database under accession number 17707.

PMID- 21851555
TI  - A novel method for monitoring the localization of cytochromes P450 and other
      endoplasmic reticulum membrane associated proteins: a tool for investigating the
      formation of metabolons.
AB  - In plants and possibly other organisms, channelling of the reactive intermediates
      resulting from P450 oxygenation is thought to require the formation of
      supramolecular complexes associating membrane-bound and soluble enzymes. This
      implies a most probably loose membrane association of the soluble proteins. For
      the assessment of such membrane association in vivo, we propose an imaging
      strategy based on the accurate evaluation of fluorescent protein repartition and
      distance around endoplasmic reticulum (ER) tubules. It requires candidate protein
      fusion constructs with fluorescent reporters and transient expression in leaves
      of Nicotiana benthamiana. The method was tested with soluble eGFP/mRFP1, with
      various P450 and P450 reductase fluorescent fusions, and with anchored
      eGFP/mRFP1. It easily differentiated soluble and anchored proteins and detects
      subtle changes in ER tubules. The method was further assessed with a soluble
      protein previously shown to be loosely associated with the ER, the phenylalanine
      ammonia lyase PAL1 involved in the lignin biosynthetic pathway. This protein was
      found located in close vicinity to the ER. Taken together, these data indicate
      that the method proposed herein is suitable to monitor membrane association and
      relocalization of soluble proteins involved in the formation of metabolons.

PMID- 21851557
TI  - The risk of rudeness.

PMID- 21851556
TI  - A transient inhibition and permanent lack of catechol-O-methyltransferase have
      minor effects on feeding pattern of female rodents.
AB  - Abnormal feeding behaviours have long been linked to disruptions in brain
      dopaminergic activity. Dopamine is metabolized, amongst others, by catechol-O
      methyltransferase (COMT). Normally, COMT only plays a subordinate role in
      dopamine metabolism. However, changes in COMT activity, especially in the
      prefrontal cortex, become more important during events that evoke dopamine
      release. The current study investigated the effect of acute COMT inhibition on
      feeding in Wistar rats and C57BL/6 mice using a selective, brain penetrating COMT
      inhibitor (OR-1139). Furthermore, the effect of a long-term lack of COMT on
      feeding behaviour was studied in COMT-deficient (COMT -/-) mice. Apart from
      following the gross feeding behaviour of fasted rats and mice, the first 4 hr of
      re-feeding were recorded with a video camera to allow a more detailed analysis of
      feeding microstructure. In the acute study, rats and mice received a single
      injection of OR-1139 (3, 10 or 30 mg/kg), just before the experiment. We found
      that rats and mice receiving OR-1139 had fewer very short meals but more long
      meals than the controls. Treated mice even ate more frequently than the controls,
      but other feeding parameters remained unchanged. Conversely, COMT -/- mice
      displayed an increased latency to initiate the first meal and spent less total
      time eating than wild-type mice. In conclusion, although decreased/lack of COMT
      activity did not robustly alter feeding behaviour of female rodents, we observed
      some alterations in the microstructure of feeding. However, these minor changes
      were highly dependent on the extent and fashion in which COMT was manipulated.

PMID- 21851558
TI  - Using narratives to trigger reflection.
AB  - BACKGROUND: During the medical course at Dundee students are taught patient
      centred medicine, and are encouraged to reflect actively upon their experiences.
      However, students often have limited familiarity with sensitive and life-changing
      events; this can make subsequent reflection superficial and of limited value.
      Many also struggle with the concept of reflection and how it can be used to
      further their personal and professional development. CONTEXT: We developed and
      ran a student-selected component (SSC) that included the study of illness
      narrative as a way of facilitating reflection and increasing student awareness of
      the patient perspective of illness. INNOVATION: Patient and doctor narratives
      were used as a proxy for patient contact, and allowed the exploration of
      sensitive topics including mental health issues, death and bereavement in a
      supportive context. Using a range of narratives we supported students in their
      reflections on these topics and identified increased self-awareness and a better
      understanding of the patient perspective. Students also discussed an intention to
      change their own practice. IMPLICATIONS: Limited opportunities may exist for
      students to develop insight into the challenges faced by doctors and patients
      presented with challenging or sensitive illness and difficult decisions. The use
      of patient and doctor narratives to facilitate discussion and encourage
      reflection on sensitive issues can offer a useful supplement to patient contact.

PMID- 21851559
TI  - The CanMEDS portfolio: a tool for reflection in a fellowship programme.
AB  - BACKGROUND: We developed a portfolio framed by the CanMEDS roles for use in a
      paediatric fellowship programme. The portfolio includes four components: a record
      of participation and achievement; career goals and professional development;
      physical evidence; and reflective writing. METHODS: Once the portfolio was in use
      for 6 months, we studied how fellows and faculty members were using the
      portfolio, and what they found to be its advantages and disadvantages. RESULTS:
      Fellows reported that it kept them organised and assisted them in setting their
      goals. They appreciated having a central place to record their accomplishments,
      as this allowed them to keep a thorough curriculum vitae. The portfolio was
      helpful in giving them the opportunity to honestly reflect on their achievements
      and setbacks, and, after reviewing this in their own minds, they were in a strong
      position to set an agenda for their meetings with supervisors. Both the fellows
      and supervisors were in agreement that the portfolio led to improved discussions
      at their meetings. Both groups also reported that this new tool was useful in
      furthering the career development of trainees, which was one of the main goals in
      its inception. Faculty supervisors also had a stronger sense of the fellows'
      work, and also of any gaps in training, as a result of using this tool.
      DISCUSSION: We hope that this reflection tool will be adapted for use in other
      training programmes. If it is introduced elsewhere, we would recommend that
      learners and staff receive ample training in its use so that it can be maximally
      effective.

PMID- 21851560
TI  - Shadowing a foundation-year doctor: a third-year medical student's perspective.
AB  - CONTEXT: This paper considers the advantages of shadowing foundation-year doctors
      (FY1) in the third year of medical school, an opportunity the UK's General
      Medical Council (UKGMC) recommends to be given to final-year students only.
      METHOD: Eighteen students spent 1 day each shadowing an FY1, holding their pager
      and carrying out their duties under direct supervision. Questionnaires, based on
      UKGMC expectations of an FY1, were completed assessing students' confidence and
      experience before and after the shifts. The doctors were interviewed. RESULTS:
      The questionnaire response rate was 72 per cent (13/18). The overall increase in
      student experiences in good clinical care (p<0.001), maintaining good medical
      practice--teaching and learning (p=0.002), and recognition and management of the
      acutely ill (p<0.001), were statistically significant. The increase in student
      confidence in answering the pager (p<0.001), prioritising jobs (p=0.002),
      venepuncture (p=0.008), writing drug charts (p=0.031), writing in patient notes
      (p=0.002) and developing management plans (p=0.002) were statistically
      significant. Qualitative results yielded an overwhelming opinion from students
      and doctors that it should be made a compulsory part of the third-year
      curriculum. The doctors found it increased their knowledge and teaching skills.
      CONCLUSION: This study has implications for the future of medical training. If
      incorporated into the third-year curriculum, compulsory shadowing would give
      students a structured one-to-one learning experience during which to learn
      clinically relevant skills. By shadowing a doctor so closely, they will also
      learn first-hand how to interact professionally with patients and other health
      care workers, a skill difficult to teach at medical school.

PMID- 21851561
TI  - Preoperative assessment clinic: a missed learning opportunity?
AB  - BACKGROUND: Day-case surgery, theatre direct admissions and elective surgery have
      revolutionised the surgical patient's pathway, and have minimised the length of
      their hospital stay. However, with large numbers of medical students placed
      mostly at teaching hospitals, this has also significantly reduced students'
      exposure to clinical signs in surgery. This study aimed to assess whether the
      preoperative assessment clinic would be an appropriate teaching arena to offer
      medical students exposure to clinical signs. METHODS: Junior doctors assigned to
      the preoperative assessment clinic were asked to fill out a specially designed
      questionnaire for each patient they reviewed. This included the planned
      operation, presenting complaint, and identification and categorisation of
      objective clinical signs on examination. The assessor was asked whether the
      patient was suitable for, and amenable to, having medical students observe. The
      presenting complaints and clinical signs were referenced to the curriculum for
      Oxford University's second Bachelor of Medicine examinations (finals). RESULTS:
      Of the 100 patients seen in 40 clinics, only four refused to be seen by a medical
      student. Of the remaining patients, 89 (92%) had presenting complaints listed on
      the core curriculum for Oxford University. Seventy-six (79%) patients had
      objective clinical signs on examination. Only three patients (3%) had neither
      clinical signs nor core relevant presenting complaints. CONCLUSIONS: The results
      clearly demonstrate that preoperative assessment is an arena that would give
      medical students two important opportunities: to examine objective clinical signs
      and to take histories of presenting complaints from the core curriculum. This
      learning opportunity would otherwise be missed.

PMID- 21851562
TI  - Jump-start to the wards: a hospitalist model.
AB  - BACKGROUND: In recent years, pursuing a second degree during medical school has
      become an increasingly attractive option. Interested students choose to leave
      medical school for one or several years, and then return to finish their clinical
      rotations. However, they often have minimal clinical exposure while completing
      these degree programmes, and may have difficulty adapting to the clinical
      environment when returning for their third or fourth year of medical school.
      CONTEXT: Whereas MD and PhD students tend to have clinical re-entry courses at
      their medical schools, there are no formal reintegration programmes for medical
      students who choose to pursue 1- or 2-year degrees. INNOVATION: We designed a 5
      day reintegration course based on a hospital service model, with physician
      assistants or nurse practitioners to aid in student transition to clinical
      rotations, and describe the experience of a dual-degree medical student
      participating in this re-entry model. IMPLICATIONS: This model provides the
      student with both didactic and patient care training, as well as the experience
      of working with professionals from different backgrounds. As the demand for dual
      degree opportunities increases, the implementation of formal re-entry programmes
      should be considered to ensure students returning to medical school are prepared
      to begin clinical rotations.

PMID- 21851563
TI  - Mental load: helping clinical learners.
AB  - BACKGROUND: The quality of an individual's learning is influenced significantly
      by the quantity of mental processing they are required to manage in a clinical
      learning situation. Some clinical learning settings require the learner to
      process high levels of complex knowledge and skills, whilst simultaneously
      monitoring and responding to challenging social or emotional inputs. This paper
      introduces the concept of 'cognitive load', its negative impacts upon novice
      learners in particular, and its real-world implications for teaching and
      supervision. METHOD: Narrative review and discussion. RESULTS: The concept of
      cognitive load is reviewed, and examples of its application to clinical learning
      and teaching are provided. Teaching and supervision strategies for managing the
      cognitive load of learners are presented. DISCUSSION: The clinical teacher has
      significant capacity to reduce the cognitive load of learners by creating safe
      and supportive learning environments, establishing trusting relationships with
      the learner, and implementing structured learning experiences that are designed
      to support the learner's growth in knowledge, understanding and skills. A
      threefold focus on the nature of the learning task, the learning environment and
      the learner's perceptions of these elements, which characterises cognitive load,
      provides a useful framework for diagnosing poor learning behaviours and
      maximising learning outcomes.

PMID- 21851565
TI  - Promoting clinical reasoning in general practice trainees: role of the clinical
      teacher.
AB  - BACKGROUND: Clinical reasoning requires knowledge, cognition and metacognition,
      and is contextually bound. Clinical teachers can and should play a key role in
      explicitly promoting clinical reasoning. CONTEXT: The aim of this article is to
      relate the clinical reasoning literature to the general practice or family
      medicine context, and to provide clinical teachers with strategies to promote
      clinical reasoning. INNOVATION: It is important that the clinical teacher teaches
      trainees the specific skills sets of the expert general practitioner (e.g.
      synthesising skills, recognising prototypes, focusing on cues and clues, using
      community resources and dealing with uncertainty) in order to promote clinical
      reasoning in the context of general practice or family medicine. Clinical
      teachers need to understand their own reasoning processes as well as be able to
      convey that knowledge to their trainees. They also need to understand the
      developmental stages of clinical reasoning and be able to nurture each trainee's
      own expertise. Strategies for facilitating effective clinical reasoning in
      trainees include adequate exposure to patients, offering the trainees opportunity
      for reflection and feedback, and coaching on the techniques of reasoning in the
      general practice context. IMPLICATIONS: The journey to expertise in clinical
      reasoning is unique to each clinician, with different skills developing at
      different rates, depending on content, context and past experience. Doctors enter
      into general practice training with the building blocks of biomedical and
      clinical knowledge and a desire to learn how to be a general practitioner.
      Clinical teachers are integral in the process of helping trainees learn how to
      'think like a general practitioner'.

PMID- 21851564
TI  - Recommended responses to lapses in professionalism.
AB  - BACKGROUND: As part of a larger project to identify appropriate responses and
      sanctions for lapses in professionalism by health profession students and
      trainees--and their teachers--we formed reference groups of medical educators to
      give preliminary guidance. We hope that these data will help to generate 'a
      greater consistency' to fitness-to-practice procedures in UK medical schools, and
      across the health professions, as called for by the UK Council for Healthcare
      Regulatory Excellence in 2009. METHODS: Having previously identified 42 forms of
      poor professionalism among students at the 'proto-professional' stage of
      undergraduate training, of which 37 could also occur in clinical teachers, we
      asked reference groups of UK medical educators (n=27) and from one medical school
      (n=35) to recommend appropriate responses by students if they observed lapses of
      professionalism in their teachers. RESULTS: There was clear congruence within and
      between the two reference groups on recommended responses for 90 per cent of the
      lapses. DISCUSSION: This congruence amounts to a broad range of consensus among
      62 UK medical educators about whether students should ignore, challenge the
      individual, discuss with peers or report the lapse to a more senior person, if
      their teachers exhibit certain behaviours. We hope that these data will help to
      generate a national consensus on appropriate responses that can be used to foster
      a culture of 'local resolution' in which juniors feel empowered to address poor
      professionalism, as well as guide undergraduate fitness to practice procedures.
      Dissemination and validation of these findings will now be undertaken.

PMID- 21851566
TI  - Leadership development for clinicians: what are we trying to achieve?
AB  - BACKGROUND: The role of all health practitioners is changing as a result of
      social, technological and demographic shifts, and clinicians are increasingly
      required to participate in leadership activities. Worldwide, there are emerging
      examples of policy agendas, professional standards and competency frameworks and
      approaches to leadership development for clinicians. CONTEXT: This article looks
      at what leadership development programmes for clinicians are trying to achieve,
      the rationale behind them and the outcomes that are deemed to be important. It
      offers a critical description of competency frameworks and their use in practice.
      INNOVATION: The UK, along with other Western countries, has embedded leadership
      and management learning outcomes into professional frameworks for students and
      qualified clinicians. There is increasing recognition that leadership development
      is best rooted in work-based activities, reflecting the realities of clinical
      life, with an emphasis on learning across the education and training continuum.
      IMPLICATIONS: If leadership is deemed to be relevant 'at all levels', then
      'leadership development' must be addressed throughout the education and training
      undertaken by health professionals. Leadership as a topic is gathering momentum
      as a key curriculum area. But effective clinical leaders and managers need to be
      nurtured and supported by the organisations and health systems within which they
      work and learn. Although a wide range of leadership development activities exist
      for individuals, without system-wide change these initiatives may not produce the
      most effective 'leadership', nor the health improvements to which they aspire.

PMID- 21851567
TI  - Clinical communication for international students in the UK undergraduate
      curriculum.
AB  - BACKGROUND: The UK's General Medical Council (GMC) emphasises effective
      communication as fundamental to good medical practice. Conversations with
      colleagues without English as a first language suggested that their needs in
      learning clinical communication skills might have differed from those of native
      English speakers. This study investigated whether training in UK medical schools
      was adequately catering for these students. METHODS: An electronic questionnaire
      was distributed to seven UK medical schools. Responses were analysed to find
      areas of concern, the most beneficial aspects of the current curriculum and
      proposals for improvements. RESULTS: In total, 151 international students
      responded. Students reported improvements in clinical communication throughout
      medical school, but concerns remain concerning 'social communication' and
      integration with peers. A majority felt that there was a need to improve clinical
      communication training specifically for international students. CONCLUSION:
      Medical schools are successful in helping international students to develop
      clinical communication skills, but could further encourage social integration.
      This could be achieved by introducing a programme linking international students
      with non-international students upon medical school entry.

PMID- 21851568
TI  - Reliability of the history and physical assessment (HAPA) form.
AB  - BACKGROUND: Medical student assessment on core clerkship rotations is notoriously
      difficult. Most evaluation is subjective and may include significant bias. This
      study aims to determine the inter-rater reliability of an objective, standardised
      history and physical examination write-up assessment (HAPA) form. METHODS: The
      HAPA form was used by two paediatrician evaluators to assess 10 student history
      and physical examination write-ups (H&Ps). Kappa scores were determined to assess
      agreement between evaluators for each HAPA form item, for the total HAPA form
      score and for an additional 'overall assessment' score. RESULTS: The kappa scores
      were relatively high, indicating good agreement between evaluators for the major
      HAPA form sections: 0.59 for data collection; 0.66 for critical reasoning; and
      0.36 for communication skills. The kappa score for the total HAPA form score was
      0.58, which was higher than the agreement derived from an 'overall assessment'
      score (0.30) that the evaluators provided for the H&P. CONCLUSIONS: A
      standardised form for H&P assessment (the HAPA form) provides superior
      reliability to the 'overall assessment' of H&Ps that is often used in clerkships
      for evaluation. Criterion-based evaluation of the student write-up can provide
      reliable evaluation and feedback to students on a clerkship.

PMID- 21851569
TI  - A novel technique for teaching the brachial plexus.
AB  - BACKGROUND: The brachial plexus has posed problems for both students and teachers
      throughout generations of medical education. The anatomy is intricate, and
      traditional pictorial representations can be difficult to understand and learn.
      Few innovative teaching methods have been reported. CONTEXT: The basic anatomy of
      the brachial plexus is core knowledge required by medical students to aid
      clinical examination and diagnosis. A more detailed understanding is necessary
      for a variety of specialists, including surgeons, anaesthetists and radiologists.
      INNOVATION: Here, we present a novel, cheap and interactive method of teaching
      the brachial plexus. Using coloured pipe cleaners, teachers and students can
      construct three-dimensional models using different colours to denote the origin
      and outflow of each nerve. The three-dimensional nature of the model also allows
      for a better understanding of certain intricacies of the plexus. Students may use
      these models as adjuncts for self study, didactic lectures and tutorials.
      IMPLICATIONS: Compared with traditional textbooks and whiteboards, the pipe
      cleaner model was preferred by medical students, and provided a higher level of
      student satisfaction. This was demonstrated and analysed using student feedback
      forms. Our model could be incorporated into current curricula to provide an
      effective and enjoyable way of rapidly teaching a difficult concept. Other such
      novel methods for teaching complex anatomical principles should be encouraged and
      explored.

PMID- 21851570
TI  - Gifts and trainees: appreciation or means of manipulation.

PMID- 21851571
TI  - Looking back on problems I encountered in problem-based learning.

PMID- 21851572
TI  - Introductions: an observational study.

PMID- 21851578
TI  - Problem-based learning, a closer look.

PMID- 21851579
TI  - Spirituality in medical education: new initiatives in Brazil.

PMID- 21851580
TI  - Medicine: a challenge for life.

PMID- 21851581
TI  - Tinnitus complaint behaviour in long-standing Meniere's disorder: its association
      with the other cardinal symptoms.
AB  - OBJECTIVE: To explore factors that determines tinnitus complaint behaviour in
      patients with chronic long-standing Meniere's disorder. DESIGN AND SETTING: A
      questionnaire-based cross-sectional investigation. This included the Oto
      neurological questionnaire, the Hearing Disability and Handicap Scale (HDHS),
      Hearing Measurement Scale (HMS) on sound localisation and the Dizziness Handicap
      Questionnaire (DHQ). PARTICIPANTS: Randomly selected 183 members of the Finnish
      Meniere's Federation. INTERVENTION: Postal questionnaire. MAIN OUTCOME MEASURE:
      International Tinnitus Inventory and impact of tinnitus. RESULTS: The 183
      patients,[36 men and 147 women; mean age, 63 years] had their Meniere's disorder
      like symptoms, with a mean of 18 years [range, 1-43], 19% of patients ranked
      tinnitus as their most severe symptom, and 10% experienced tinnitus as causing a
      severe or very severe impact. Regression analysis indicated that 41% of
      International Tinnitus Inventory variance and 28% of tinnitus impact variance
      were explained by the cardinal symptoms of Meniere's disorder. Furthermore, 40%
      of International Tinnitus Inventory and 25% of tinnitus impact variance were
      explained by symptom-related disabilities (HDHS, HMS and DHQ). Aural pressure,
      hearing loss and gait problems were the most important predictors of tinnitus
      complaint. Understanding what people say and limitation of activities because of
      vertigo were the most important related disabilities. CONCLUSION: Tinnitus shares
      a significant variance with the other cardinal symptoms in patients with long
      standing Meniere's disorder. As the impact is significantly related to activity
      limitations based on hearing disability and vertigo, the results suggest that
      therapeutic efforts to reduce tinnitus in Meniere's disorder should include the
      alleviation of balance and hearing problems.

PMID- 21851582
TI  - Attitudes and knowledge of child and adolescent mental health clinicians in
      relation to the psychosis risk syndrome.
AB  - AIM: To evaluate the knowledge and attitudes of clinicians in a Child and
      Adolescent Mental Health Service in relation to the 'At-Risk Mental State'
      concept in psychosis. METHODS: A questionnaire was constructed and administered
      to child and adolescent mental health clinicians working in North East England.
      RESULTS: Sixty-seven per cent (n=121) of eligible clinicians responded. Almost
      all the participants believed that young people 'At-Risk' needed support.
      However, only around half felt confident in identifying this patient group.
      Approximately a third felt that antipsychotic medication may be useful. Some
      interprofessional differences were noted in relation to both knowledge and
      attitudes. CONCLUSIONS: Further training would be required for most health
      workers in this sample to feel confident in identifying the syndrome. These
      findings require replication in other service settings and may have implications
      for the implementation of a Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition, diagnostic category relating to the At-Risk Mental
      State.

PMID- 21851583
TI  - UV tanning--the problem that does not go away.

PMID- 21851585
TI  - Combining multivariate analysis and monosaccharide composition modeling to
      identify plant cell wall variations by Fourier Transform Near Infrared
      spectroscopy.
AB  - We outline a high throughput procedure that improves outlier detection in cell
      wall screens using FT-NIR spectroscopy of plant leaves. The improvement relies on
      generating a calibration set from a subset of a mutant population by taking
      advantage of the Mahalanobis distance outlier scheme to construct a
      monosaccharide range predictive model using PLS regression. This model was then
      used to identify specific monosaccharide outliers from the mutant population.

PMID- 21851586
TI  - Early identification of young children at risk for poor academic achievement:
      preliminary development of a parent-report prediction tool.
AB  - BACKGROUND: Early school success is clearly related to later health. A prediction
      index that uses parent report to assess children's risk for poor academic
      achievement could potentially direct targeted service delivery to improve child
      outcomes. METHODS: We obtained risk factors through literature review and used
      the National Longitudinal Survey of Youth 1979 Child Files to examine the
      predictive associations of these factors with academic achievement scores.
      RESULTS: Twenty predictors were identified including four strong predictors
      (maternal education, child gender, family income, and low birth weight).
      Significantly, 12 predictors explained 17-24% of score variance. CONCLUSIONS:
      Parent-reported factors provide predictive accuracy for academic achievement.

PMID- 21851587
TI  - Rationale, design and methods for a randomised and controlled trial of the impact
      of virtual reality games on motor competence, physical activity, and mental
      health in children with developmental coordination disorder.
AB  - BACKGROUND: A healthy start to life requires adequate motor development and
      physical activity participation. Currently 5-15% of children have impaired motor
      development without any obvious disorder. These children are at greater risk of
      obesity, musculoskeletal disorders, low social confidence and poor mental health.
      Traditional electronic game use may impact on motor development and physical
      activity creating a vicious cycle. However new virtual reality (VR) game
      interfaces may provide motor experiences that enhance motor development and lead
      to an increase in motor coordination and better physical activity and mental
      health outcomes. VR games are beginning to be used for rehabilitation, however
      there is no reported trial of the impact of these games on motor coordination in
      children with developmental coordination disorder. METHODS: This cross-over
      randomised and controlled trial will examine whether motor coordination is
      enhanced by access to active electronic games and whether daily activity,
      attitudes to physical activity and mental health are also enhanced. Thirty
      children aged 10-12 years with poor motor coordination (<= 15th percentile) will
      be recruited and randomised to a balanced ordering of 'no active electronic
      games' and 'active electronic games'. Each child will participate in both
      conditions for 16 weeks, and be assessed prior to participation and at the end of
      each condition. The primary outcome is motor coordination, assessed by kinematic
      and kinetic motion analysis laboratory measures. Physical activity and sedentary
      behaviour will be assessed by accelerometry, coordination in daily life by parent
      report questionnaire and attitudes to physical activity, self-confidence, anxiety
      and depressed mood will be assessed by self report questionnaire. A sample of 30
      will provide a power of > 0.9 for detecting a 5 point difference in motor
      coordination on the MABC-2 TIS scale (mean 17, sd = 5). DISCUSSION: This is the
      first trial to examine the impact of new virtual reality games on motor
      coordination in children with developmental coordination disorder. The findings
      will provide critical information to understand whether these electronic games
      can be used to have a positive impact on the physical and mental health of these
      children. Given the importance of adequate motor coordination, physical activity
      and mental health in childhood, this project can inform interventions which could
      have a profound impact on the long term health of this group of children. TRIAL
      REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR):
      ACTRN12611000400965.

PMID- 21851588
TI  - Genome-wide copy number variation (CNV) in patients with autoimmune Addison's
      disease.
AB  - BACKGROUND: Addison's disease (AD) is caused by an autoimmune destruction of the
      adrenal cortex. The pathogenesis is multi-factorial, involving genetic components
      and hitherto unknown environmental factors. The aim of the present study was to
      investigate if gene dosage in the form of copy number variation (CNV) could add
      to the repertoire of genetic susceptibility to autoimmune AD. METHODS: A genome
      wide study using the Affymetrix GeneChip(r) Genome-Wide Human SNP Array 6.0 was
      conducted in 26 patients with AD. CNVs in selected genes were further
      investigated in a larger material of patients with autoimmune AD (n = 352) and
      healthy controls (n = 353) by duplex Taqman real-time polymerase chain reaction
      assays. RESULTS: We found that low copy number of UGT2B28 was significantly more
      frequent in AD patients compared to controls; conversely high copy number of
      ADAM3A was associated with AD. CONCLUSIONS: We have identified two novel CNV
      associations to ADAM3A and UGT2B28 in AD. The mechanism by which this
      susceptibility is conferred is at present unclear, but may involve steroid
      inactivation (UGT2B28) and T cell maturation (ADAM3A). Characterization of these
      proteins may unravel novel information on the pathogenesis of autoimmunity.

PMID- 21851589
TI  - Reducing the worst case running times of a family of RNA and CFG problems, using
      Valiant's approach.
AB  - BACKGROUND: RNA secondary structure prediction is a mainstream bioinformatic
      domain, and is key to computational analysis of functional RNA. In more than 30
      years, much research has been devoted to defining different variants of RNA
      structure prediction problems, and to developing techniques for improving
      prediction quality. Nevertheless, most of the algorithms in this field follow a
      similar dynamic programming approach as that presented by Nussinov and Jacobson
      in the late 70's, which typically yields cubic worst case running time
      algorithms. Recently, some algorithmic approaches were applied to improve the
      complexity of these algorithms, motivated by new discoveries in the RNA domain
      and by the need to efficiently analyze the increasing amount of accumulated
      genome-wide data. RESULTS: We study Valiant's classical algorithm for Context
      Free Grammar recognition in sub-cubic time, and extract features that are common
      to problems on which Valiant's approach can be applied. Based on this, we
      describe several problem templates, and formulate generic algorithms that use
      Valiant's technique and can be applied to all problems which abide by these
      templates, including many problems within the world of RNA Secondary Structures
      and Context Free Grammars. CONCLUSIONS: The algorithms presented in this paper
      improve the theoretical asymptotic worst case running time bounds for a large
      family of important problems. It is also possible that the suggested techniques
      could be applied to yield a practical speedup for these problems. For some of the
      problems (such as computing the RNA partition function and base-pair binding
      probabilities), the presented techniques are the only ones which are currently
      known for reducing the asymptotic running time bounds of the standard algorithms.

PMID- 21851590
TI  - A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1.
AB  - BACKGROUND: The cell-cycle checkpoint kinase Chk1 is essential in mammalian cells
      due to its roles in controlling processes such as DNA replication, mitosis and
      DNA-damage responses. Despite its paramount importance, how Chk1 controls these
      functions remains unclear, mainly because very few Chk1 substrates have hitherto
      been identified. RESULTS: Here, we combine a chemical genetics approach with high
      resolution mass spectrometry to identify novel Chk1 substrates and their
      phosphorylation sites. The list of targets produced reveals the potential impact
      of Chk1 function not only on processes where Chk1 was already known to be
      involved, but also on other key cellular events such as transcription, RNA
      splicing and cell fate determination. In addition, we validate and explore the
      phosphorylation of transcriptional co-repressor KAP1 Ser473 as a novel DNA-damage
      induced Chk1 site. CONCLUSIONS: By providing a substantial set of potential Chk1
      substrates, we present opportunities for studying unanticipated functions for
      Chk1 in controlling a wide range of cellular processes. We also refine the Chk1
      consensus sequence, facilitating the future prediction of Chk1 target sites. In
      addition, our identification of KAP1 Ser473 phosphorylation as a robust readout
      for Chk1 activity could be used to explore the in vivo effects of Chk1 inhibitors
      that are being developed for clinical evaluation.

PMID- 21851591
TI  - PARalyzer: definition of RNA binding sites from PAR-CLIP short-read sequence
      data.
AB  - Crosslinking and immunoprecipitation (CLIP) protocols have made it possible to
      identify transcriptome-wide RNA-protein interaction sites. In particular, PAR
      CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. We
      present an approach, centered on the novel PARalyzer tool, for mapping high
      confidence sites from PAR-CLIP deep-sequencing data. We show that PARalyzer
      delineates sites with a high signal-to-noise ratio. Motif finding identifies the
      sequence preferences of RNA-binding proteins, as well as seed-matches for highly
      expressed microRNAs when profiling Argonaute proteins. Our study describes
      tailored analytical methods and provides guidelines for future efforts to utilize
      high-throughput sequencing in RNA biology. PARalyzer is available at
      http://www.genome.duke.edu/labs/ohler/research/PARalyzer/.

PMID- 21851593
TI  - The Baron's complaint.

PMID- 21851592
TI  - The taming of an impossible child: a standardized all-in approach to the
      phylogeny of Hymenoptera using public database sequences.
AB  - BACKGROUND: Enormous molecular sequence data have been accumulated over the past
      several years and are still exponentially growing with the use of faster and
      cheaper sequencing techniques. There is high and widespread interest in using
      these data for phylogenetic analyses. However, the amount of data that one can
      retrieve from public sequence repositories is virtually impossible to tame
      without dedicated software that automates processes. Here we present a novel
      bioinformatics pipeline for downloading, formatting, filtering and analyzing
      public sequence data deposited in GenBank. It combines some well-established
      programs with numerous newly developed software tools (available at
      http://software.zfmk.de/). RESULTS: We used the bioinformatics pipeline to
      investigate the phylogeny of the megadiverse insect order Hymenoptera (sawflies,
      bees, wasps and ants) by retrieving and processing more than 120,000 sequences
      and by selecting subsets under the criteria of compositional homogeneity and
      defined levels of density and overlap. Tree reconstruction was done with a
      partitioned maximum likelihood analysis from a supermatrix with more than 80,000
      sites and more than 1,100 species. In the inferred tree, consistent with previous
      studies, "Symphyta" is paraphyletic. Within Apocrita, our analysis suggests a
      topology of Stephanoidea + (Ichneumonoidea + (Proctotrupomorpha + (Evanioidea +
      Aculeata))). Despite the huge amount of data, we identified several persistent
      problems in the Hymenoptera tree. Data coverage is still extremely low, and
      additional data have to be collected to reliably infer the phylogeny of
      Hymenoptera. CONCLUSIONS: While we applied our bioinformatics pipeline to
      Hymenoptera, we designed the approach to be as general as possible. With this
      pipeline, it is possible to produce phylogenetic trees for any taxonomic group
      and to monitor new data and tree robustness in a taxon of interest. It therefore
      has great potential to meet the challenges of the phylogenomic era and to deepen
      our understanding of the tree of life.

PMID- 21851595
TI  - Layer-dependent nanoscale electrical properties of graphene studied by conductive
      scanning probe microscopy.
AB  - The nanoscale electrical properties of single-layer graphene (SLG), bilayer
      graphene (BLG) and multilayer graphene (MLG) are studied by scanning capacitance
      microscopy (SCM) and electrostatic force microscopy (EFM). The quantum
      capacitance of graphene deduced from SCM results is found to increase with the
      layer number (n) at the sample bias of 0 V but decreases with n at -3 V.
      Furthermore, the quantum capacitance increases very rapidly with the gate voltage
      for SLG, but this increase is much slowed down when n becomes greater. On the
      other hand, the magnitude of the EFM phase shift with respect to the SiO2
      substrate increases with n at the sample bias of +2 V but decreases with n at -2
      V. The difference in both quantum capacitance and EFM phase shift is significant
      between SLG and BLG but becomes much weaker between MLGs with a different n. The
      layer-dependent quantum capacitance behaviors of graphene could be attributed to
      their layer-dependent electronic structure as well as the layer-varied dependence
      on gate voltage, while the layer-dependent EFM phase shift is caused by not only
      the layer-dependent surface potential but also the layer-dependent capacitance
      derivation.

PMID- 21851594
TI  - Study protocol of the multi-site randomised controlled REDALI-DEM trial--the
      effects of structured relearning methods on daily living task performance of
      persons with dementia.
AB  - BACKGROUND: Evidence from pilot trials suggests that structured learning
      techniques may have positive effects on the performance of cognitive tasks,
      movement sequences or skills in patients with Alzheimer's disease. The purpose of
      this trial is to evaluate whether the usual method of learning by trial and error
      or the method of errorless learning demonstrate better effects on the performance
      of two selected daily living tasks six weeks after the intervention in people
      with mild to moderate dementia. METHODS/DESIGN: A seven-centre single-blind,
      active-controlled design with a 1:1 randomisation for two parallel groups will
      include 175 persons diagnosed with Alzheimer's disease or mixed type dementia
      (MMSE 14-24), living at home, showing at least moderate need for assistance in
      instrumental activities of daily living; primary carer available and informed
      consent of patient and primary carer. Patients of both study arms will receive 15
      one-hour-sessions at home by trained interventionists practising two daily living
      tasks individually selected. In one group the trial and error technique and in
      the other group the errorless learning method will be applied. Primary outcome is
      the task performance measured with the Task Performance Scale six weeks post
      treatment. DISCUSSION: The trial results will inform us to improve guidelines for
      instructing individuals with memory impairments. A user-friendly practice
      guideline will allow an efficient implementation of structured relearning
      techniques for a wide range of service providers in dementia care. TRIAL
      REGISTRATION: DRKS00003117.

PMID- 21851596
TI  - Experiences of the implementation of a tool for lifestyle intervention in primary
      health care: a qualitative study among managers and professional groups.
AB  - BACKGROUND: In recent years there has been increasing interest in transferring
      new knowledge into health care practices, a process often referred to as
      implementation. The various subcultures that exist among health care workers may
      be an obstacle in this process. The aim of this study was to explore how
      professional groups and managers experienced the implementation of a new tool for
      lifestyle intervention in primary health care (PHC). The computer-based tool was
      introduced with the intention of facilitating the delivery of preventive
      services. METHODS: Focus group interviews with staff and individual interviews
      with managers at six PHC units in the southeast of Sweden were performed 9 months
      after the introduction of the new working tool. Staff interviews were conducted
      in groups according to profession, and were analysed using manifest content
      analysis. Experiences and opinions from the different staff groups and from
      managers were analysed. RESULTS: Implementation preconditions, opinions about the
      lifestyle test, and opinions about usage were the main areas identified. In each
      of the groups, managers and professionals, factors related to the existing
      subcultures seemed to influence their experiences of the implementation. Managers
      were visionary, GPs were reluctant, nurses were open, and nurse assistants were
      indifferent. CONCLUSION: This study indicates that the existing subcultures in
      PHC influence how the implementation of an innovation is perceived by managers
      and the different professionals. In PHC, an organization with several subcultures
      and an established hierarchical structure, an implementation strategy aimed at
      all groups did not seem to result in a successful uptake of the new method.

PMID- 21851597
TI  - Microstructural and Mossbauer properties of low temperature synthesized Ni-Cd-Al
      ferrite nanoparticles.
AB  - We report the influence of Al3+ doping on the microstructural and Mossbauer
      properties of ferrite nanoparticles of basic composition Ni0.2Cd0.3Fe2.5 - xAlxO4
      (0.0 <= x <= 0.5) prepared through simple sol-gel method. X-ray diffraction
      (XRD), scanning electron microscopy (SEM), energy dispersive X-ray, transmission
      electron microscopy (TEM), Fourier transformation infrared (FTIR), and Mossbauer
      spectroscopy techniques were used to investigate the structural, chemical, and
      Mossbauer properties of the grown nanoparticles. XRD results confirm that all the
      samples are single-phase cubic spinel in structure excluding the presence of any
      secondary phase corresponding to any structure. SEM micrographs show the
      synthesized nanoparticles are agglomerated but spherical in shape. The average
      crystallite size of the grown nanoparticles was calculated through Scherrer
      formula and confirmed by TEM and was found between 2 and 8 nm (+/- 1). FTIR
      results show the presence of two vibrational bands corresponding to tetrahedral
      and octahedral sites. Mossbauer spectroscopy shows that all the samples exhibit
      superparamagnetism, and the quadrupole interaction increases with the
      substitution of Al3+ ions.

PMID- 21851598
TI  - Development and application of a modified dynamic time warping algorithm (DTW-S)
      to analyses of primate brain expression time series.
AB  - BACKGROUND: Comparing biological time series data across different conditions, or
      different specimens, is a common but still challenging task. Algorithms aligning
      two time series represent a valuable tool for such comparisons. While many
      powerful computation tools for time series alignment have been developed, they do
      not provide significance estimates for time shift measurements. RESULTS: Here, we
      present an extended version of the original DTW algorithm that allows us to
      determine the significance of time shift estimates in time series alignments, the
      DTW-Significance (DTW-S) algorithm. The DTW-S combines important properties of
      the original algorithm and other published time series alignment tools: DTW-S
      calculates the optimal alignment for each time point of each gene, it uses
      interpolated time points for time shift estimation, and it does not require
      alignment of the time-series end points. As a new feature, we implement a
      simulation procedure based on parameters estimated from real time series data, on
      a series-by-series basis, allowing us to determine the false positive rate (FPR)
      and the significance of the estimated time shift values. We assess the
      performance of our method using simulation data and real expression time series
      from two published primate brain expression datasets. Our results show that this
      method can provide accurate and robust time shift estimates for each time point
      on a gene-by-gene basis. Using these estimates, we are able to uncover novel
      features of the biological processes underlying human brain development and
      maturation. CONCLUSIONS: The DTW-S provides a convenient tool for calculating
      accurate and robust time shift estimates at each time point for each gene, based
      on time series data. The estimates can be used to uncover novel biological
      features of the system being studied. The DTW-S is freely available as an R
      package TimeShift at http://www.picb.ac.cn/Comparative/data.html.

PMID- 21851599
TI  - Catalytic pyrolysis of Laminaria japonica over nanoporous catalysts using Py
      GC/MS.
AB  - The catalytic pyrolysis of Laminaria japonica was carried out over a
      hierarchical meso-MFI zeolite (Meso-MFI) and nanoporous Al-MCM-48 using pyrolysis
      gas chromatography/mass spectrometry (Py-GC/MS). The effect of the catalyst type
      on the product distribution and chemical composition of the bio-oil was examined
      using Py-GC/MS. The Meso-MFI exhibited a higher activity in deoxygenation and
      aromatization during the catalytic pyrolysis of L. japonica. Meanwhile, the
      catalytic activity of Al-MCM-48 was lower than that of Meso-MFI due to its weak
      acidity.

PMID- 21851600
TI  - Areca nut chewing and dependency syndrome: is the dependence comparable to
      smoking? a cross sectional study.
AB  - BACKGROUND: Areca nut is the seed of fruit oriental palm known as Areca catechu.
      Many adverse effects of nut chewing have been well documented in the medical
      literature. As these nuts are mixed with some other substances like tobacco and
      flavouring agents, it has been hypothesized that it might also cause some
      dependency symptoms among its users. Therefore, the objective of this study was
      to investigate dependency syndrome among areca nut users with and without tobacco
      additives and compare it with dependency associated with cigarette smoking among
      the male Pakistani population. METHODS: This was an observational cross sectional
      study carried out on healthy individuals, who were users of any one of the three
      products (areca nut only, areca nut with tobacco additives, cigarette smokers).
      Participants were selected by convenience sampling of people coming to hospital
      to seek a free oral check up. Information was collected about the socio
      demographic profile, pattern of use and symptoms of dependency using the DSM-IV
      criteria for substance dependence. We carried out multiple logistic regressions
      to investigate association between socio-demographic profile, pattern of
      substance use and dependency syndrome. RESULTS: We carried out final analysis on
      851 individuals, of which 36.8% (n = 314) were areca nut users, 28.4% (n = 242)
      were the chewers of areca with tobacco additives and 34.7% (n = 295) were regular
      cigarette smokers. Multivariate analyses showed that individuals using areca nut
      with tobacco additives were significantly more likely to have dependency syndrome
      (OR = 2.17, 95% CI 1.39-3.40) while cigarette smokers were eight times more
      likely to have dependency syndrome as compared to areca nut only users.
      CONCLUSIONS: Areca nut use with and without tobacco additives was significantly
      associated with dependency syndrome. In comparison to exclusive areca nut users,
      the smokers were eight times more likely to develop dependence while areca nut
      users with tobacco additives were also significantly more likely to suffer from
      the dependence.

PMID- 21851601
TI  - Biclonal myelodysplastic syndrome involving six chromosomes and monoallelic loss
      of RB1 - A rare case.
AB  - BACKGROUND: Myelodysplastic syndrome (MDS) represents a group of clonal
      hematological disorders characterized by progressive cytopenia, and reflects to
      defects in erythroid, myeloid and megakaryocytic maturation. MDS is more
      frequently observed in older aged patients with cytogenetic abnormalities like
      monosomy of chromosome(s) 5 and/or 7. In 50% of de novo MDS cases, chromosomal
      aberrations are found and rearrangements involving the retinoblastoma (RB1) gene
      in 13q14 are found. RESULTS: Here, we are presenting a case report of a rare
      biclonal MDS with a karyotype of 45, XY,-4, der(6)t(4;6)(p15.1;p21.3),
      der(8)t(4;8)(q31.2;q22), t(13;16)(q21.3;p11.2)11/45, XY,
      der(7)t(7;13)(p22.2~22.3;q21.3),-13 9. The patient was diagnosed according to WHO
      classification as refractory anemia with excess of blasts (RAEB
      II).Immunophenotyping was positive for CD11b, CD11c, CD10, CD13, CD15, CD16 and
      CD33. CONCLUSION: We report, a novel and cytogenetically rare case of a biclonal
      MDS with complex chromosomal aberrations and deletion of RB1-gene in both clones.
      These findings are associated with a poor prognosis as the patient died 3 months
      after diagnosis.

PMID- 21851602
TI  - Protocol for minimizing the risk of metachronous adenomas of the colorectum with
      green tea extract (MIRACLE): a randomised controlled trial of green tea extract
      versus placebo for nutriprevention of metachronous colon adenomas in the elderly
      population.
AB  - BACKGROUND: Prevention of colorectal cancer is a major health care issue. People
      who have undergone colonoscopy screening and had colorectal polyps removed have a
      higher risk of being diagnosed with polyps again compared to the normal
      population. Therefore, it would be ideal to find appropriate means that
      effectively help to prevent the reoccurrence of polyps after polypectomy. So far,
      pharmaceutical chemoprevention with NSAIDs including aspirin has been shown to be
      effective but not gained general acceptance due to side effects. Nutraceuticals
      such as polyphenols from tea plants have demonstrated remarkable therapeutic and
      preventive effects in molecular, epidemiological and clinical trials. However,
      placebo-controlled trials demonstrating the efficacy of nutraceuticals for the
      (secondary) prevention of colorectal polyps as precursors for colorectal cancer
      are missing. METHODS/DESIGN: We present the design of a randomized, placebo
      controlled, multicentre trial to investigate the effect of diet supplementation
      with green tea extract containing 300 mg epigallocatechin gallate (EGCG), the
      major polyphenol in green tea, on the recurrence of colon adenomas. Patients who
      have undergone polypectomy for colonic polyps will be randomized to receive
      either green tea extract containing 150 mg EGCG two times daily or a placebo over
      the course of three years. After a one month run-in period in which all patients
      will receive the active intervention, 2534 patients will be randomized, and 2028
      patients are expected to complete the whole study course. Incidence, number and
      histology of adenoma at endpoint colonoscopy at three years will be compared in
      both groups. DISCUSSION: The beneficial safety profile of decaffeinated green tea
      extract, the quantifiable and known active content EGCG, and the accumulating
      evidence of its cancer preventive potential require, in our view, a validation of
      this compound for the nutriprevention of colorectal adenoma. Good accessibility
      and low costs might render this neutraceutical a top candidate for wider use as
      food supplement in colon cancer prevention. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01360320.

PMID- 21851603
TI  - Analysing GCN4 translational control in yeast by stochastic chemical kinetics
      modelling and simulation.
AB  - BACKGROUND: The yeast Saccharomyces cerevisiae responds to amino acid starvation
      by inducing the transcription factor Gcn4. This is mainly mediated via a
      translational control mechanism dependent upon the translation initiation
      eIF2.GTP.Met-tRNAiMet ternary complex, and the four short upstream open reading
      frames (uORFs) in its 5' mRNA leader. These uORFs act to attenuate GCN4 mRNA
      translation under normal conditions. During amino acid starvation, levels of
      ternary complex are reduced. This overcomes the GCN4 translation attenuation
      effect via a scanning/reinitiation control mechanism dependent upon uORF spacing.
      RESULTS: Using published experimental data, we have developed and validated a
      probabilistic formulation of GCN4 translation using the Chemical Master Equation
      (Model 1). Model 1 explains GCN4 translation's nonlinear dependency upon uORF
      placements, and predicts that an as yet unidentified factor, which was proposed
      to regulate GCN4 translation under some conditions, only has pronounced effects
      upon GCN4 translation when intercistronic distances are unnaturally short. A
      simpler Model 2 that does not include this unidentified factor could well
      represent the regulation of a natural GCN4 mRNA. Using parameter values optimised
      for this algebraic Model 2, we performed stochastic simulations by Gillespie
      algorithm to investigate the distribution of ribosomes in different sections of
      GCN4 mRNA under distinct conditions. Our simulations demonstrated that ribosomal
      loading in the 5'-untranslated region is mainly determined by the ratio between
      the rates of 5'-initiation and ribosome scanning, but was not significantly
      affected by rate of ternary complex binding. Importantly, the translation rate
      for codons starved of cognate tRNAs is predicted to be the most significant
      contributor to the changes in ribosomal loading in the coding region under
      repressing and derepressing conditions. CONCLUSIONS: Our integrated probabilistic
      Models 1 and 2 explained GCN4 translation and helped to elucidate the role of a
      yet unidentified factor. The ensuing stochastic simulations evaluated different
      factors that may impact on the translation of GCN4 mRNA, and integrated
      translation status with ribosomal density.

PMID- 21851604
TI  - Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6
      mice.
AB  - BACKGROUND: Multi-walled carbon nanotubes (MWCNTs) are widely used in many
      disciplines due to their unique physical and chemical properties. Therefore, some
      concerns about the possible human health and environmental impacts of
      manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs
      impairs pulmonary function in C57BL/6 mice due to development of lung
      inflammation and fibrosis. METHODS: MWCNTs were administered to C57BL/6 mice by
      oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation
      and fibrosis by inflammatory cell infiltration, collagen content, and
      histological assessment. Pulmonary function was assessed using a FlexiVent system
      and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.
      RESULTS: Mice administered MWCNTs exhibited increased inflammatory cell
      infiltration, collagen deposition and granuloma formation in lung tissue, which
      correlated with impaired pulmonary function as assessed by increased resistance,
      tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs
      induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and
      Ccl11), and protease production (Mmp13) that promoted the inflammatory and
      fibrotic changes observed within the lung. CONCLUSIONS: These results further
      highlight the potential adverse health effects that may occur following MWCNT
      exposure and therefore we suggest these materials may pose a significant risk
      leading to impaired lung function following environmental and occupational
      exposures.

PMID- 21851605
TI  - Cholesterol-enriched diet causes age-related macular degeneration-like pathology
      in rabbit retina.
AB  - BACKGROUND: Alzheimer's disease (AD) and age-related macular degeneration (AMD)
      share several pathological hallmarks including beta-amyloid (Abeta) accumulation,
      oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely
      multi-factorial with several factors such as diet, environment, and genetic
      susceptibility participating in the pathogenesis of these diseases.
      Epidemiological studies correlated high plasma cholesterol levels with high
      incidence of AD, and feeding rabbits with a diet rich in cholesterol has been
      shown to induce AD-like pathology in rabbit brain. High intake of cholesterol and
      saturated fat were also long been suspected to increase the risk for AMD.
      However, the extent to which cholesterol-enriched diet may also cause AMD-like
      features in rabbit retinas is not well known. METHODS: Male New Zealand white
      rabbits were fed normal chow or a 2% cholesterol-enriched diet for 12 weeks. At
      necropsy, animals were perfused with Dulbecco's phosphate-buffered saline and the
      eyes were promptly removed. One eye of each animal was used for
      immunohistochemistry and retina dissected from the other eye was used for Western
      blot, ELISA assays, spectrophotometry and mass spectrometry analyses. RESULTS:
      Increased levels of Abeta, decreased levels of the anti-apoptotic protein Bcl-2,
      increased levels of the pro-apoptotic Bax and gadd153 proteins, emergence of
      TUNEL-positive cells, and increased generation of reactive oxygen species were
      found in retinas from cholesterol-fed compared to normal chow-fed rabbits.
      Additionally, astrogliosis, drusen-like debris and cholesterol accumulations in
      retinas from cholesterol-fed rabbits were observed. As several lines of evidence
      suggest that oxidized cholesterol metabolites (oxysterols) may be the link by
      which cholesterol contributes to the pathogenesis of AMD, we determined levels of
      oxysterols and found a dramatic increase in levels of oxysterols in retinas from
      cholesterol-fed rabbits. CONCLUSIONS: Our results suggest that cholesterol
      enriched diets cause retinal degeneration that is relevant to AMD. Furthermore,
      our data suggests high cholesterol levels and subsequent increase in the
      cholesterol metabolites as potential culprits to AMD.

PMID- 21851606
TI  - Accuracy and differential bias in copy number measurement of CCL3L1 in
      association studies with three auto-immune disorders.
AB  - BACKGROUND: Copy number variation (CNV) contributes to the variation observed
      between individuals and can influence human disease progression, but the accurate
      measurement of individual copy numbers is technically challenging. In the work
      presented here we describe a modification to a previously described paralogue
      ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region,
      which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As
      the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we
      performed case control association studies with Crohn's disease, rheumatoid
      arthritis and psoriasis clinical cohorts. RESULTS: We evaluate the PRT
      methodology used, paying particular attention to accuracy and precision, and
      highlight the problems of differential bias in copy number measurements. Our PRT
      methods for measuring copy number were of sufficient precision to detect very
      slight but systematic differential bias between results from case and control DNA
      samples in one study. We find no evidence for an association between CCL3L1 copy
      number and Crohn's disease, rheumatoid arthritis or psoriasis. CONCLUSIONS:
      Differential bias of this small magnitude, but applied systematically across
      large numbers of samples, would create a serious risk of false positive
      associations in copy number, if measured using methods of lower precision, or
      methods relying on single uncorroborated measurements. In this study the small
      differential bias detected by PRT in one sample set was resolved by a simple pre
      treatment by restriction enzyme digestion.

PMID- 21851607
TI  - Renal and suprarenal insufficiency secondary to familial Mediterranean fever
      associated with amyloidosis: a case report.
AB  - INTRODUCTION: Familial Mediterranean fever is an autosomal recessive disease that
      predominantly affects people of the Mediterranean coast. One of the most frequent
      complications of the disease is amyloidosis. This clinical entity is known as
      secondary (also called AA) amyloidosis. CASE PRESENTATION: In this report, we
      describe the case of a 33-year-old Turkish man with familial Mediterranean fever
      and chronic renal insufficiency. He was admitted to our clinic with symptoms of
      suprarenal insufficiency. The patient died three months later as a result of
      cardiac arrest. CONCLUSION: Our aim is to make a contribution to the literature
      by reporting a case of combined insufficiency due to the accumulation of renal
      and adrenal amyloid in a patient with familial Mediterranean fever, which has
      very rarely been described in the literature. We hope that adrenal insufficiency,
      which becomes fatal if not diagnosed and treated rapidly, will come to mind as
      easily as chronic renal failure in clinical practice.

PMID- 21851609
TI  - Sudden massive neck swelling due to hemorrhage of a thyroid adenoma: a case
      report.
AB  - INTRODUCTION: Sudden swelling of the neck is an emergency situation that can be
      life-threatening for the patient. Therefore, an understanding of the possible
      underlying pathology is of great importance. Sudden massive swelling of the neck
      because of intralesional bleeding of a thyroid adenoma is seldom encountered but
      must be considered. Such massive swelling caused by spontaneous bleeding of a
      thyroid adenoma has not yet been described in the literature. CASE PRESENTATION:
      We report the case of a 71-year-old Caucasian man with sudden massive neck
      swelling due to intralesional bleeding of a thyroid adenoma. We present his
      clinical history, physical examination results, computed tomography (CT) scans,
      and histological findings after surgery. He presented with sudden massive
      swelling of the left side of his neck after sneezing while working with his hands
      over his head. An ear, nose, and throat examination showed a painless swelling of
      the left side of his neck and a displacement of his larynx to the right. CT scans
      revealed a mass originating from the left lobe of his thyroid gland and the mass
      displaced his larynx and trachea. A surgical exploration showed a greatly
      enlarged left lobe of his thyroid gland. A histopathological examination showed a
      hemorrhagic infarction of a follicular thyroid adenoma. CONCLUSIONS: Sudden
      intralesional bleeding of a thyroid adenoma is a rare condition but one that
      should be considered in cases of sudden and massive swelling of the neck.

PMID- 21851608
TI  - Anandamide inhibits Theiler's virus induced VCAM-1 in brain endothelial cells and
      reduces leukocyte transmigration in a model of blood brain barrier by activation
      of CB(1) receptors.
AB  - BACKGROUND: VCAM-1 represents one of the most important adhesion molecule
      involved in the transmigration of blood leukocytes across the blood-brain barrier
      (BBB) that is an essential step in the pathogenesis of MS. Several evidences have
      suggested the potential therapeutic value of cannabinoids (CBs) in the treatment
      of MS and their experimental models. However, the effects of endocannabinoids on
      VCAM-1 regulation are poorly understood. In the present study we investigated the
      effects of anandamide (AEA) in the regulation of VCAM-1 expression induced by
      Theiler's virus (TMEV) infection of brain endothelial cells using in vitro and in
      vivo approaches. METHODS: i) in vitro: VCAM-1 was measured by ELISA in
      supernatants of brain endothelial cells infected with TMEV and subjected to AEA
      and/or cannabinoid receptors antagonist treatment. To evaluate the functional
      effect of VCAM-1 modulation we developed a blood brain barrier model based on a
      system of astrocytes and brain endothelial cells co-culture. ii) in vivo: CB(1)
      receptor deficient mice (Cnr1(-/-)) infected with TMEV were treated with the AEA
      uptake inhibitor UCM-707 for three days. VCAM-1 expression and microglial
      reactivity were evaluated by immunohistochemistry. RESULTS: Anandamide-induced
      inhibition of VCAM-1 expression in brain endothelial cell cultures was mediated
      by activation of CB(1) receptors. The study of leukocyte transmigration confirmed
      the functional relevance of VCAM-1 inhibition by AEA. In vivo approaches also
      showed that the inhibition of AEA uptake reduced the expression of brain VCAM-1
      in response to TMEV infection. Although a decreased expression of VCAM-1 by UCM
      707 was observed in both, wild type and CB(1) receptor deficient mice (Cnr1(-/
      )), the magnitude of VCAM-1 inhibition was significantly higher in the wild type
      mice. Interestingly, Cnr1(-/-) mice showed enhanced microglial reactivity and
      VCAM-1 expression following TMEV infection, indicating that the lack of CB(1)
      receptor exacerbated neuroinflammation. CONCLUSIONS: Our results suggest that
      CB(1) receptor dependent VCAM-1 inhibition is a novel mechanism for AEA-reduced
      leukocyte transmigration and contribute to a better understanding of the
      mechanisms underlying the beneficial role of endocannabinoid system in the
      Theiler's virus model of MS.

PMID- 21851610
TI  - Utilisation of malaria preventive measures during pregnancy and birth outcomes in
      Ibadan, Nigeria.
AB  - BACKGROUND: Malaria remains a major public health problem in sub Saharan Africa
      and the extent of utilisation of malaria preventive measures may impact on the
      burden of malaria in pregnancy. This study sought to determine the association
      between malaria preventive measures utilized during pregnancy and the birth
      outcomes of birth weight and preterm delivery. METHODS: This cross sectional
      survey involved 800 mothers who delivered at the University College Hospital, and
      Adeoyo Maternity Hospital, Ibadan. Data obtained included obstetric information,
      gestational age, birth weight and self reported use of malaria prevention
      strategies in index pregnancy. RESULTS: Most (95.6%) mothers used one or more
      malaria control measures. The most commonly used vector control measures were
      window net (84.0%), insecticide spray (71.5%) and insecticide treated bed nets
      (20.1%), while chemoprophylactic agents were pyrimethamine (23.5%), Intermittent
      Preventive Treatments with Sulphadoxine-Pyrimethamine (IPTsp) (18.5%) and
      intermittent chloroquine (9.5%) and 21.7% used herbal medications. The mean +/-
      SD birthweight and gestational age of the babies were 3.02 kg +/- 0.56 and 37.9
      weeks +/- 2.5 respectively. Preterm delivery rate was 19.4% and 9% had low birth
      weight. Comparing babies whose mothers had IPTsp with those who did not, mean
      birth weight was 3.13 kg +/- 0.52 versus 3.0 kg +/- 0.56 (p = 0.016) and mean
      gestational age was 38.5 weeks +/- 2.1 versus 37.8 weeks +/- 2.5 (p = 0.002). The
      non-use of IPTsp was associated with increased risk of having low birth weight
      babies (AOR: 2.27, 95% CI: 0.98; 5.28) and preterm birth (AOR: 1.93, 95% CI:
      1.08, 3.44). The non use of herbal preparations (AOR: 0.55, 95% CI: 0.36, 0.85)
      was associated with reduced risk of preterm birth. The mean +/- SD birth weight
      and gestational ages of babies born to mothers who slept under ITNs were not
      significantly different from those who did not (p = 0.07 and 0.09 respectively).
      CONCLUSIONS: There is a need for improved utilisation of IPTsp as well as
      discouraging the use of herbal medications in pregnancy in order to reduce
      pregnancy outcome measures of low birth weight and preterm deliveries in this
      environment.

PMID- 21851611
TI  - Are elderly people with co-morbidities involved adequately in medical decision
      making when hospitalised? A cross-sectional survey.
AB  - BACKGROUND: Medical decision making has long been in focus, but little is known
      of the preferences and conditions for elderly people with co-morbidities to
      participate in medical decision making. The main objective of the present study
      was to investigate the preferred and the actual degree of control, i.e. the role
      elderly people with co-morbidities wish to assume and actually had with regard to
      information and participation in medical decision making during their last stay
      in hospital.This study was a cross-sectional survey including three Swedish
      hospitals with acute admittance. The participants were patients aged 75 years and
      above with three or more diagnoses according to the International Classification
      of Diseases (ICD-10) and three or more hospitalisations during the last year.
      METHODS: We used a questionnaire combined with a telephone interview, using the
      Control Preference Scale to measure each participant's preferred and actual role
      in medical decision making during their last stay in hospital. Additional
      questions were asked about barriers to participation in decision making and
      preferred information seeking role. The results are presented with descriptive
      statistics with kappa weights. RESULTS: Of the 297 elderly patients identified,
      52.5% responded (n = 156, 46.5% male). Mean age was 83.1 years. Of the
      respondents, 42 of 153 patients said that they were not asked for their opinion
      (i.e. no shared decision making). Among the other 111 patients, 49 had their
      exact preferred level of participation, 37 had less participation than they would
      have preferred, and 23 had more responsibility than they would have preferred.
      Kappa statistics showed a moderate agreement between preferred and actual role
      (kappaw = 0.57; 95% CI: 0.45-0.69). Most patients wanted to be given more
      information without having to ask. There was no correlation between age, gender,
      or education and preferred role. 35% of the patients agreed that they experienced
      some of the various barriers to decision making that they were asked about: 1)
      the severity of their illness, 2) doctors with different treatment strategies, 3)
      difficulty understanding the medical information, and 4) difficulty understanding
      doctors who did not speak the patient's own language. CONCLUSIONS: Physicians are
      not fully responsive to patient preferences regarding either the degree of
      communication or the patient's participation in decision making. Barriers to
      participation can be a problem, and should be taken into account more often when
      dealing with hospitalised elderly people.

PMID- 21851612
TI  - Body mass index has a curvilinear relationship with the percentage of body fat
      among children.
AB  - BACKGROUND: Body Mass Index (BMI), which is defined as the ratio between weight
      (in kg) and height (in m2), is often used in clinical practice as well as in
      large scale epidemiological studies to classify subjects as underweight, normal
      weight, overweight or obese. Although BMI does not directly measure the
      percentage of Body Fat (BF%), it is widely applied because it is strongly related
      with BF%, it is easy to measure and it is an important predictor of mortality.
      Among children, age and sex-specific reference values of BMI, known as
      percentiles, are used. However, it is not clear how strong the relationship
      between BMI and BF% is among children and whether the association is linear. We
      performed a cross-sectional study aiming at evaluating the strength and shape of
      the relationship between BMI and BF% among school-aged children aged 6-12 years.
      FINDINGS: The study was conducted on a sample of 361 football-playing male
      children aged 6 to 12 years in Rome, Italy. Age, weight, height and skinfold
      thickness were collected. BF% was estimated using 4 skinfold equations whereas
      BMI was converted into BMI-for-age z-score. The relationship between these
      variables was examined using linear regression analyses. Mean BMI was 18.2 (+/-
      2.8), whereas BF% was influenced by the skinfold equation used, with mean values
      ranging from 15.6% to 23.0%. A curvilinear relationship between BMI-for-age
      zscore and BF % was found, with the regression line being convex. The association
      between BMI-for-age zscore and BF% was stronger among overweight/obese children
      than among normal/underweight children. This curvilinear pattern was evident in
      all 4 skinfold equations used. CONCLUSIONS: The association between BMI-for-age
      zscore and BF% is not linear among male children aged 6-12 years and it is
      stronger among overweight and obese subjects than among normal and underweight
      subjects. In this age group, BMI is a valid index of adiposity only among
      overweight and obese subjects.

PMID- 21851613
TI  - Applying the theory of planned behaviour to explain HIV testing in antenatal
      settings in Addis Ababa - a cohort study.
AB  - BACKGROUND: To facilitate access to the prevention of mother-to-child HIV
      transmission (PMTCT) services, HIV counselling and testing are offered routinely
      in antenatal care settings. Focusing a cohort of pregnant women attending public
      and private antenatal care facilities, this study applied an extended version of
      the Theory of Planned Behaviour (TPB) to explain intended- and actual HIV
      testing. METHODS: A sequential exploratory mixed methods study was conducted in
      Addis Ababa in 2009. The study involved first time antenatal attendees from
      public- and private health care facilities. Three Focus Group Discussions were
      conducted to inform the TPB questionnaire. A total of 3033 women completed the
      baseline TPB interviews, including attitudes, subjective norms, perceived
      behavioural control and intention with respect to HIV testing, whereas 2928
      completed actual HIV testing at follow up. Data were analysed using descriptive
      statistics, Chi-square tests, Fisher's Exact tests, Internal consistency
      reliability, Pearson's correlation, Linear regression, Logistic regression and
      using Epidemiological indices. P-values < 0.05 was considered significant and 95%
      Confidence Interval (CI) was used for the odds ratio. RESULTS: The TPB explained
      9.2% and 16.4% of the variance in intention among public- and private health
      facility attendees. Intention and perceived barriers explained 2.4% and external
      variables explained 7% of the total variance in HIV testing. Positive and
      negative predictive values of intention were 96% and 6% respectively. Across both
      groups, subjective norm explained a substantial amount of variance in intention,
      followed by attitudes. Women intended to test for HIV if they perceived social
      support and anticipated positive consequences following test performance. Type of
      counselling did not modify the link between intended and actual HIV testing.
      CONCLUSION: The TPB explained substantial amount of variance in intention to test
      but was less sufficient in explaining actual HIV testing. This low explanatory
      power of TPB was mainly due to the large proportion of low intenders that ended
      up being tested contrary to their intention before entering the antenatal clinic.
      PMTCT programs should strengthen women's intention through social approval and
      information that testing will provide positive consequences for them. However,
      women's rights to opt-out should be emphasized in any attempt to improve the
      PMTCT programs.

PMID- 21851614
TI  - Instrumented intervertebral or posterolateral fusion in elderly patients:
      clinical results of a single center.
AB  - BACKGROUND: Data on the clinical outcome after spinal fusion in the elderly
      patient are rare. To our knowledge there has been no clinical outcome assessment
      for instrumented spinal fusion in elderly patients comparing posterolateral
      fusion with intervertebral fusion. Aim of the current study was to evaluate the
      clinical outcome of elderly patients who underwent a spinal fusion procedure for
      degenerative spinal stenosis with instability. Main hypothesis was to test
      whether it is necessary to force an intervertebral fusion for a better clinical
      outcome in spinal fusion surgery of the elderly or not. METHODS: Two subgroups -
      posterolateral fusion versus intervertebral fusion (cage vs. non-cage) were
      compared with regard to functional outcome, fusion rates and complications after
      a mean follow up of 3.8 years. Questionnaires were completed by the patients
      before surgery and at final follow-up. Changes in mean VAS and ODI scores
      (decrease from the baseline VAS and ODI scores) were compared. RESULTS: The mean
      final follow up for all subjects was 3.8 years. Of the 114 patients, 2 patients
      were deceased at the time of the follow-up, 5 patients didn't want to participate
      and 107 patients completed the questionnaires. This resulted in an overall follow
      up rate of 93%. At final follow-up, the patients demonstrated significant
      improvement in the VAS and ODI- compared with the preoperative scores in both
      groups. But overall there were no significant differences between both groups
      regarding the outcome assessment using the ODI and VAS. CONCLUSIONS: The results
      of this study shows that elderly patients aged over 75 benefit from instrumented
      lumbar fusion. The study suggests that there is no need to force an
      intervertebral fusion because elderly patients do not seem to benefit from this
      procedure.

PMID- 21851615
TI  - Mechanisms underlying purinergic P2X3 receptor-mediated mechanical allodynia
      induced in diabetic rats.
AB  - BACKGROUND: Diabetic neuropathy is a common neuropathy associated with
      paresthaesia and pain. The mechanisms underlying the painful conditions are not
      well understood. The aim of this study is to investigate the participation of
      purinergic P2X3 receptors in painful diabetic neuropathy. RESULTS: Diabetes was
      induced by an intraperitoneal injection of streptozotocin (STZ). We showed that
      mechanical allodynia was induced two weeks after a STZ injection and lasted for
      at least another seven weeks. The mechanical allodynia was significantly
      attenuated by peripheral administration of the P2X receptor antagonists, PPADS or
      TNP-ATP. DiI was subcutaneously injected into the rat hindpaw to label hindpaw
      innervated dorsal root ganglion (DRG) neurons. ATP activated fast-inactivating
      P2X3 receptor-mediated currents in the labeled DRG neurons were studied. ATP
      responses in STZ-treated rats were ~2-fold larger than those in control rats.
      Furthermore, the expression of P2X3 receptor proteins in the plasma membrane of
      L4-6 DRGs of STZ rats was significantly enhanced while the total expression of
      P2X3 receptors remained unaltered. CONCLUSIONS: These results indicate that a
      large enhancement of P2X3 receptor activity and an increase in the membrane
      expression of P2X3 receptors contribute to the development of chronic pain in STZ
      induced diabetic rats and suggest a possible target for the treatment of diabetic
      neuropathic pain.

PMID- 21851616
TI  - Psychometric validation of the revised SCOPA-Diary Card: expanding the
      measurement of non-motor symptoms in Parkinson's disease.
AB  - BACKGROUND: To identify key non-motor symptoms of Parkinson's disease (PD) to
      include in a daily diary assessment for off-time, revise the Scales for Outcomes
      of Parkinson's disease Diary Card (SCOPA-DC) to include these non-motor symptoms,
      and investigate the validity, reliability and predictive utility of the Revised
      SCOPA-DC in a U.S. population. METHODS: A convenience sample was used to recruit
      four focus groups of PD patients. Based on findings from focus groups, the SCOPA
      DC was revised and administered to a sample of 101 PD patients. Confirmatory
      factor analysis was conducted to test the domain structure of the Revised SCOPA
      DC. The reliability, convergent and discriminant validity, and ability to predict
      off-time of the Revised SCOPA-DC were then assessed. RESULTS: Based on input from
      PD patients, the Revised SCOPA-DC included several format changes and the
      addition of non-motor symptoms. The Revised SCOPA-DC was best represented by a
      three-factor structure: Mobility, Physical Functioning and Psychological
      Functioning. Correlations between the Revised SCOPA-DC and other Health-Related
      Quality of Life scores were supportive of convergent validity. Known-groups
      validity analyses indicated that scores on the Revised SCOPA-DC were lower among
      patients who reported experiencing off-time when compared to those without off
      time. The three subscales had satisfactory predictive utility, correctly
      predicting off-time slightly over two-thirds of the time. CONCLUSIONS: These
      findings provide evidence of content validity of the Revised SCOPA-DC and suggest
      that a three-factor structure is an appropriate model that provides reliable and
      valid scores to assess symptom severity among PD patients with symptom
      fluctuations in the U.S.

PMID- 21851617
TI  - Uncovering tacit knowledge: a pilot study to broaden the concept of knowledge in
      knowledge translation.
AB  - BACKGROUND: All sectors in health care are being asked to focus on the knowledge
      to-practice gap, or knowledge translation, to increase service effectiveness. A
      social interaction approach to knowledge translation assumes that research
      evidence becomes integrated with previously held knowledge, and practitioners
      build on and co-create knowledge through mutual interactions. Knowledge
      translation strategies for public health have not provided anticipated positive
      changes in evidence-based practice, possibly due in part to a narrow
      conceptualization of knowledge. More work is needed to understand the role of
      tacit knowledge in decision-making and practice. This pilot study examined how
      health practitioners applied tacit knowledge in public health program planning
      and implementation. METHODS: This study used a narrative approach, where teams
      from two public health units in Ontario, Canada were conveniently selected.
      Respondents participated in individual interviews and focus groups at each site.
      Questions were designed to understand the role of tacit knowledge as it related
      to the program planning process. Data were analyzed through a combination of
      content analysis and thematic comparison. RESULTS: The findings highlighted two
      major aspects of knowledge that arose: the use of tacit knowledge and the
      integration of tacit and explicit knowledge. Tacit knowledge included: past
      experiences, organization-specific knowledge, community contextual knowledge, and
      the recognition of the tacit knowledge of others. Explicit knowledge included:
      research literature, the Internet, popular magazines, formal assessments (surveys
      and interviews), legislation and regulations. Participants sometimes deliberately
      combined tacit and explicit knowledge sources in planning. CONCLUSIONS: This
      pilot demonstrated that front-line public health workers draw upon both tacit
      knowledge and explicit knowledge in their everyday lived reality. Further, tacit
      knowledge plays an important role in practitioners' interpretation and
      implementation of explicit research findings. This indicates a need to broaden
      the scope of knowledge translation to include other forms of knowledge beyond
      explicit knowledge acquired through research. Strategies that recognize and
      support the use of tacit knowledge, such as communities of practice or networks,
      may be important components of a comprehensive approach to knowledge translation.
      This study provides support for further investigation of the role of tacit
      knowledge in the planning and delivery of effective public health services.

PMID- 21851618
TI  - Test-retest of computerized health status questionnaires frequently used in the
      monitoring of knee osteoarthritis: a randomized crossover trial.
AB  - BACKGROUND: To compare data based on touch screen to data based on traditional
      paper versions of questionnaires frequently used to examine patient reported
      outcomes in knee osteoarthritis patients and to examine the impact of patient
      characteristics on this comparison METHODS: Participants were recruited from an
      ongoing trial (http://ClinicalTrials.Gov Identifier: NCT00655941). 20 female
      participants, mean age 67 (SD 7), completed KOOS, VAS pain, function and patient
      global, SF-36, Physical Activity Scale, painDETECT, and the ADL Taxonomy.
      Patients were randomly assigned to one of two subgroups, completing either the
      paper or touch screen version first. Mean, mean differences (95% CI), median,
      median differences and Intraclass Correlation Coefficients (ICCs) were calculated
      for all questionnaires. RESULTS: ICCs between data based on computerized and
      paper versions ranged from 0.86 to 0.99. Analysis revealed a statistically
      significant difference between versions of the ADL Taxonomy, but not for the
      remaining questionnaires. Age, computer experience or education-level had no
      significant impact on the results. The computerized questionnaires were reported
      to be easier to use. CONCLUSION: The computerized questionnaires gave comparable
      results to answers given on paper. Patient characteristics did not influence
      results and implementation was feasible.

PMID- 21851619
TI  - Accounting for genomic pre-selection in national BLUP evaluations in dairy
      cattle.
AB  - BACKGROUND: In future Best Linear Unbiased Prediction (BLUP) evaluations of dairy
      cattle, genomic selection of young sires will cause evaluation biases and loss of
      accuracy once the selected ones get progeny. METHODS: To avoid such bias in the
      estimation of breeding values, we propose to include information on all genotyped
      bulls, including the culled ones, in BLUP evaluations. Estimated breeding values
      based on genomic information were converted into genomic pseudo-performances and
      then analyzed simultaneously with actual performances. Using simulations based on
      actual data from the French Holstein population, bias and accuracy of BLUP
      evaluations were computed for young sires undergoing progeny testing or genomic
      pre-selection. For bulls pre-selected based on their genomic profile, three
      different types of information can be included in the BLUP evaluations: (1) data
      from pre-selected genotyped candidate bulls with actual performances on their
      daughters, (2) data from bulls with both actual and genomic pseudo-performances,
      or (3) data from all the genotyped candidates with genomic pseudo-performances.
      The effects of different levels of heritability, genomic pre-selection intensity
      and accuracy of genomic evaluation were considered. RESULTS: Including
      information from all the genotyped candidates, i.e. genomic pseudo-performances
      for both selected and culled candidates, removed bias from genetic evaluation and
      increased accuracy. This approach was effective regardless of the magnitude of
      the initial bias and as long as the accuracy of the genomic evaluations was
      sufficiently high. CONCLUSIONS: The proposed method can be easily and quickly
      implemented in BLUP evaluations at the national level, although some improvement
      is necessary to more accurately propagate genomic information from genotyped to
      non-genotyped animals. In addition, it is a convenient method to combine direct
      genomic, phenotypic and pedigree-based information in a multiple-step procedure.

PMID- 21851620
TI  - High incidence of medication documentation errors in a Swiss university hospital
      due to the handwritten prescription process.
AB  - BACKGROUND: Medication errors have been reported to be a leading cause of death
      in hospitalized patients. In this study we focused on identifying and quantifying
      errors in the handwritten drug ordering and dispensing documentation processes
      which could possibly lead to adverse drug events. METHODS: We studied 1,934
      ordered agents (165 consecutive patients) retrospectively for medication
      documentation errors. Errors were categorized into: Prescribing errors,
      transcription errors and administration documentation errors on the nurses'
      medication lists. The legibility of prescriptions was analyzed to explore its
      possible influence on the error rate in the documentation process. RESULTS:
      Documentation errors occurred in 65 of 1,934 prescribed agents (3.5%). The
      incidence of patient charts showing at least one error was 43%. Prescribing
      errors were found 39 times (37%), transcription errors 56 times (53%), and
      administration documentation errors 10 times (10%). The handwriting readability
      was rated as good in 2%, moderate in 42%, bad in 52%, and unreadable in 4%.
      CONCLUSIONS: This study revealed a high incidence of documentation errors in the
      traditional handwritten prescription process. Most errors occurred when
      prescriptions were transcribed into the patients' chart. The readability of the
      handwritten prescriptions was generally bad. Replacing the traditional
      handwritten documentation process with information technology could potentially
      improve the safety in the medication process.

PMID- 21851621
TI  - Bacterial adaptation during chronic infection revealed by independent component
      analysis of transcriptomic data.
AB  - BACKGROUND: Bacteria employ a variety of adaptation strategies during the course
      of chronic infections. Understanding bacterial adaptation can facilitate the
      identification of novel drug targets for better treatment of infectious diseases.
      Transcriptome profiling is a comprehensive and high-throughput approach for
      characterization of bacterial clinical isolates from infections. However,
      exploitation of the complex, noisy and high-dimensional transcriptomic dataset is
      difficult and often hindered by low statistical power. RESULTS: In this study, we
      have applied two kinds of unsupervised analysis methods, principle component
      analysis (PCA) and independent component analysis (ICA), to extract and
      characterize the most informative features from transcriptomic dataset generated
      from cystic fibrosis (CF) Pseudomonas aeruginosa isolates. ICA was shown to be
      able to efficiently extract biological meaningful features from the
      transcriptomic dataset and improve clustering patterns of CF isolates.
      Decomposition of the transcriptomic dataset by ICA also facilitates gene
      identification and gene ontology enrichment. CONCLUSIONS: Our results show that
      P. aeruginosa employs multiple patient-specific adaption strategies during the
      early stage infections while certain essential adaptations are evolved in
      parallel during the chronic infections.

PMID- 21851622
TI  - High lifetime pregnancy and low contraceptive usage among sex workers who use
      drugs- an unmet reproductive health need.
AB  - BACKGROUND: The objective of this study was to describe levels of pregnancy and
      contraceptive usage among a cohort of street-based female sex workers (FSWs) in
      Vancouver. METHODS: The study sample was obtained from a community-based
      prospective cohort study (2006-2008) of 211 women in street-based sex work who
      use drugs, 176 of whom had reported at least one prior pregnancy. Descriptive
      statistics were used to estimate lifetime pregnancy prevalence, pregnancy
      outcomes (miscarriage, abortion, adoption, child apprehension, child custody),
      and contraceptive usage. In secondary analyses, associations between
      contraceptive usage, individual and interpersonal risk factors and high number of
      lifetime pregnancies (defined as greater than the sample mean of 4) were
      examined. RESULTS: Among our sample, 84% reported a prior pregnancy, with a mean
      of 4 lifetime pregnancies (median = 3; IQR: 2-5). The median age of women
      reporting 5+ pregnancies was 38 years old [interquartile range (IQR): 25.0-39.0]
      compared to 34 years [IQR: 25.0-39.0] among women reporting 4 or fewer prior
      pregnancies. 45% were Caucasian and 47% were of Aboriginal ancestry. We observed
      high rates of previous abortion (median = 1;IQR:1-3), apprehension (median = 2;
      IQR:1-4) and adoption (median = 1; IQR:1-2) among FSWs who reported prior
      pregnancy. The use of hormonal and insertive contraceptives was limited. In
      bivariate analysis, tubal ligation (OR = 2.49; [95%CI = 1.14-5.45]), and
      permanent contraceptives (e.g., tubal ligation and hysterectomy) (OR = 2.76;
      [95%CI = 1.36-5.59]) were both significantly associated with having five or more
      pregnancies. CONCLUSION: These findings demonstrate high levels of unwanted
      pregnancy in the context of low utilization of effective contraceptives and
      suggest a need to improve the accessibility and utilization of reproductive
      health services, including family planning, which are appropriately targeted and
      tailored for FSWs in Vancouver.

PMID- 21851623
TI  - Transcripts that associate with the RNA binding protein, DEAD-END (DND1), in
      embryonic stem (ES) cells.
AB  - BACKGROUND: The RNA binding protein, DEAD END (DND1), is essential for
      maintaining viable germ cells in vertebrates. It is also a testicular germ cell
      tumor susceptibility factor in mice. DND1 has been shown to interact with the 3'
      untranslated region (3'-UTR) of mRNAs such as P27 and LATS2. Binding of DND1 to
      the 3'-UTRs of these transcripts blocks the inhibitory function of microRNAs
      (miRNA) from these transcripts and in this way DND1 helps maintain P27 and LATS2
      protein expression. We found that DND1 is also expressed in embryonic stem (ES)
      cells. Because ES cells share similar gene expression patterns as germ cells, we
      utilized ES cells to identify additional candidate mRNAs that associate with
      DND1. RESULTS: ES cells are readily amenable to genetic modification and easier
      to culture in vitro compared to germ cells. Therefore, for the purpose of our
      study, we made a genetically modified, stable, human embryonic stem (hES) cell
      line that expresses hemagluttinin (HA)-tagged DND1 in a doxycycline (dox)
      regulatable manner. This line expresses modest levels of HA-DND1 and serves as a
      good system to study DND1 function in vitro. We used this stable cell line to
      identify the transcripts that physically interact with DND1. By performing
      ribonucleoprotein immunoprecipitation (RIP) followed by RT-PCR, we identified
      that transcripts encoding pluripotency factors (OCT4, SOX2, NANOG, LIN28), cell
      cycle regulators (TP53, LATS2) and apoptotic factors (BCLX, BAX) are specifically
      associated with the HA-DND1 ribonucleoprotein complex. Surprisingly, in many
      cases, bioinformatics analysis of the pulled-down transcripts did not reveal the
      presence of known DND1 interacting motifs. CONCLUSIONS: Our results indicate that
      the inducible ES cell line system serves as a suitable in vitro system to
      identify the mRNA targets of DND1. The RIP-RT results hint at the broad spectrum
      of mRNA targets that interact with DND1 in ES cells. Based on what is known about
      DND1 function, our results suggest that DND1 may impose another level of
      translational regulation to modulate expression of critical factors in ES cells.

PMID- 21851624
TI  - MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer
      cells by targeting oncogene BMI-1.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) is the key process driving
      cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce
      EMT in cancer cells. Recent studies have implied that noncoding microRNAs
      (miRNAs) act as crucial modulators for EMT. The aims of this study was to
      determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and
      the possible role of miRNA in controlling BMI-1 expression. METHODS AND RESULTS:
      We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and
      detected a strong association with invasive capability. Stable silencing of BMI-1
      in invasive mesenchymal-type EC cells up-regulated the epithelial marker E
      cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced
      cell invasion in vitro. Furthermore, we discovered that the expression of BMI-1
      was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region
      3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to
      epithelial transition (MET) by restoring E-cadherin, reducing Vimentin
      expression, and inhibiting cell invasion in vitro. Moreover, BMI-1 knockdown
      inhibited in vitro EC cell proliferation and clone growth, correlated with either
      increased p16 expression or decreased expression of stem cell and chemoresistance
      markers (SOX-2, KLF4 and MRP-1). CONCLUSION: These findings demonstrate the novel
      mechanism for BMI-1 in contributing to EC cell invasion and that repression of
      BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.

PMID- 21851625
TI  - Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years
      of experience in Cambodia.
AB  - Whilst some populations have recently experienced dramatic declines in malaria,
      the majority of those most at risk of Plasmodium falciparum malaria still lack
      access to effective treatment with artemisinin combination therapy (ACT) and
      others are already facing parasites resistant to artemisinins.In this context,
      there is a crucial need to improve both access to and targeting of ACT through
      greater availability of good quality ACT and parasitological diagnosis. This is
      an issue of increasing urgency notably in the private commercial sector, which,
      in many countries, plays an important role in the provision of malaria treatment.
      The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that
      aims to increase the provision of affordable ACT in public, private and NGO
      sectors through a manufacturer-level subsidy. However, to date, there is little
      documented experience in the programmatic implementation of subsidized ACT in the
      private sector. Cambodia is in the unique position of having more than 10 years
      of experience not only in implementing subsidized ACT, but also rapid diagnostic
      tests (RDT) as part of a nationwide social marketing programme. The programme
      includes behaviour change communication and the training of private providers as
      well as the sale and distribution of Malarine, the recommended ACT, and
      Malacheck, the RDT. This paper describes and evaluates this experience by drawing
      on the results of household and provider surveys conducted since the start of the
      programme. The available evidence suggests that providers' and consumers'
      awareness of Malarine increased rapidly, but that of Malacheck much less so. In
      addition, improvements in ACT and RDT availability and uptake were relatively
      slow, particularly in more remote areas.The lack of standardization in the survey
      methods and the gaps in the data highlight the importance of establishing a clear
      system for monitoring and evaluation for similar initiatives. Despite these
      limitations, a number of important lessons can still be learnt. These include the
      importance of a comprehensive communications strategy and of a sustained and
      reliable supply of products, with attention to the geographical reach of both.
      Other important challenges relate to the difficulty in incentivising providers
      and consumers not only to choose the recommended drug, but to precede this with a
      confirmatory blood test and ensure that providers adhere to the test results and
      patients to the treatment regime. In Cambodia, this is particularly complicated
      due to problems inherent to the drug itself and the emergence of artemisinin
      resistance.

PMID- 21851626
TI  - Nephele: genotyping via complete composition vectors and MapReduce.
AB  - BACKGROUND: Current sequencing technology makes it practical to sequence many
      samples of a given organism, raising new challenges for the processing and
      interpretation of large genomics data sets with associated metadata. Traditional
      computational phylogenetic methods are ideal for studying the evolution of
      gene/protein families and using those to infer the evolution of an organism, but
      are less than ideal for the study of the whole organism mainly due to the
      presence of insertions/deletions/rearrangements. These methods provide the
      researcher with the ability to group a set of samples into distinct genotypic
      groups based on sequence similarity, which can then be associated with metadata,
      such as host information, pathogenicity, and time or location of occurrence.
      Genotyping is critical to understanding, at a genomic level, the origin and
      spread of infectious diseases. Increasingly, genotyping is coming into use for
      disease surveillance activities, as well as for microbial forensics. The classic
      genotyping approach has been based on phylogenetic analysis, starting with a
      multiple sequence alignment. Genotypes are then established by expert examination
      of phylogenetic trees. However, these traditional single-processor methods are
      suboptimal for rapidly growing sequence datasets being generated by next
      generation DNA sequencing machines, because they increase in computational
      complexity quickly with the number of sequences. RESULTS: Nephele is a suite of
      tools that uses the complete composition vector algorithm to represent each
      sequence in the dataset as a vector derived from its constituent k-mers by
      passing the need for multiple sequence alignment, and affinity propagation
      clustering to group the sequences into genotypes based on a distance measure over
      the vectors. Our methods produce results that correlate well with expert-defined
      clades or genotypes, at a fraction of the computational cost of traditional
      phylogenetic methods run on traditional hardware. Nephele can use the open-source
      Hadoop implementation of MapReduce to parallelize execution using multiple
      compute nodes. We were able to generate a neighbour-joined tree of over 10,000
      16S samples in less than 2 hours. CONCLUSIONS: We conclude that using Nephele can
      substantially decrease the processing time required for generating genotype trees
      of tens to hundreds of organisms at genome scale sequence coverage.

PMID- 21851627
TI  - Patterns of comorbidity in community-dwelling older people hospitalised for fall
      related injury: a cluster analysis.
AB  - BACKGROUND: Community-dwelling older people aged 65+ years sustain falls
      frequently; these can result in physical injuries necessitating medical attention
      including emergency department care and hospitalisation. Certain health
      conditions and impairments have been shown to contribute independently to the
      risk of falling or experiencing a fall injury, suggesting that individuals with
      these conditions or impairments should be the focus of falls prevention. Since
      older people commonly have multiple conditions/impairments, knowledge about which
      conditions/impairments coexist in at-risk individuals would be valuable in the
      implementation of a targeted prevention approach. The objective of this study was
      therefore to examine the prevalence and patterns of comorbidity in this
      population group. METHODS: We analysed hospitalisation data from Victoria,
      Australia's second most populous state, to estimate the prevalence of comorbidity
      in patients hospitalised at least once between 2005-6 and 2007-8 for treatment of
      acute fall-related injuries. In patients with two or more comorbid conditions
      (multicomorbidity) we used an agglomerative hierarchical clustering method to
      cluster comorbidity variables and identify constellations of conditions. RESULTS:
      More than one in four patients had at least one comorbid condition and among
      patients with comorbidity one in three had multicomorbidity (range 2-7). The
      prevalence of comorbidity varied by gender, age group, ethnicity and injury type;
      it was also associated with a significant increase in the average cumulative
      length of stay per patient. The cluster analysis identified five distinct,
      biologically plausible clusters of comorbidity: cardiopulmonary/metabolic,
      neurological, sensory, stroke and cancer. The cardiopulmonary/metabolic cluster
      was the largest cluster among the clusters identified. CONCLUSIONS: The
      consequences of comorbidity clustering in terms of falls and/or injury outcomes
      of hospitalised patients should be investigated by future studies. Our findings
      have particular relevance for falls prevention strategies, clinical practice and
      planning of follow-up services for these patients.

PMID- 21851628
TI  - DARS-RNP and QUASI-RNP: new statistical potentials for protein-RNA docking.
AB  - BACKGROUND: Protein-RNA interactions play fundamental roles in many biological
      processes. Understanding the molecular mechanism of protein-RNA recognition and
      formation of protein-RNA complexes is a major challenge in structural biology.
      Unfortunately, the experimental determination of protein-RNA complexes is tedious
      and difficult, both by X-ray crystallography and NMR. For many interacting
      proteins and RNAs the individual structures are available, enabling computational
      prediction of complex structures by computational docking. However, methods for
      protein-RNA docking remain scarce, in particular in comparison to the numerous
      methods for protein-protein docking. RESULTS: We developed two medium-resolution,
      knowledge-based potentials for scoring protein-RNA models obtained by docking:
      the quasi-chemical potential (QUASI-RNP) and the Decoys As the Reference State
      potential (DARS-RNP). Both potentials use a coarse-grained representation for
      both RNA and protein molecules and are capable of dealing with RNA structures
      with posttranscriptionally modified residues. We compared the discriminative
      power of DARS-RNP and QUASI-RNP for selecting rigid-body docking poses with the
      potentials previously developed by the Varani and Fernandez groups. CONCLUSIONS:
      In both bound and unbound docking tests, DARS-RNP showed the highest ability to
      identify native-like structures. Python implementations of DARS-RNP and QUASI-RNP
      are freely available for download at http://iimcb.genesilico.pl/RNP/

PMID- 21851630
TI  - Isolated complete avulsion of the gallbladder (near traumatic cholecystectomy): a
      case report and review of the literature.
AB  - INTRODUCTION: Injury of the gallbladder after blunt abdominal trauma is an
      unusual finding; the reported incidence is less than 2%. Three groups of injuries
      are described: simple contusion, laceration, and avulsion, the last of which can
      be partial, complete, or total traumatic cholecystectomy. CASE PRESENTATION: A
      case of isolated complete avulsion of the gallbladder (near traumatic
      cholecystectomy) from its hepatic bed in a 46-year-old Caucasian man without any
      other sign of injury is presented. The avulsion was due to blunt abdominal trauma
      after a car accident. The rarity of this injury and the stable condition of our
      patient at the initial presentation warrant a description. The diagnosis was made
      incidentally after a computed tomography scan, and our patient was treated
      successfully with ligation of the cystic duct and artery, removal of the
      gallbladder, coagulation of the bleeding points, and placement of a drain.
      CONCLUSIONS: Early diagnosis of such injuries is quite difficult because
      abdominal signs are poor, non-specific, or even absent. Therefore, a computed
      tomography scan should be performed when the mechanism of injury is indicated.

PMID- 21851629
TI  - Recent trends in chronic disease, impairment and disability among older adults in
      the United States.
AB  - BACKGROUND: To examine concurrent prevalence trends of chronic disease,
      impairment and disability among older adults. METHODS: We analyzed the 1998, 2004
      and 2008 waves of the Health and Retirement Study, a nationally representative
      survey of older adults in the United States, and included 31,568 community
      dwelling adults aged 65 and over. Measurements include: prevalence of chronic
      diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic
      lung disease and arthritis; prevalence of impairments, including impairments of
      cognition, vision, hearing, mobility, and urinary incontinence; prevalence of
      disability, including activities of daily living (ADLs) and instrumental
      activities of daily living (IADLs). RESULTS: The proportion of older adults
      reporting no chronic disease decreased from 13.1% (95% Confidence Interval [CI],
      12.4%-13.8%) in 1998 to 7.8% (95% CI, 7.2%-8.4%) in 2008, whereas the proportion
      reporting 1 or more chronic diseases increased from 86.9% (95% CI, 86.2%-89.6%)
      in 1998 to 92.2% (95% CI, 91.6%-92.8%) in 2008. In addition, the proportion
      reporting 4 or more diseases increased from 11.7% (95% CI, 11.0%-12.4%) in 1998
      to 17.4% (95% CI, 16.6%-18.2%) in 2008. The proportion of older adults reporting
      no impairments was 47.3% (95% CI, 46.3%-48.4%) in 1998 and 44.4% (95% CI, 43.3%
      45.5%) in 2008, whereas the proportion of respondents reporting 3 or more was
      7.2% (95% CI, 6.7%-7.7%) in 1998 and 7.3% (95% CI, 6.8%-7.9%) in 2008. The
      proportion of older adults reporting any ADL or IADL disability was 26.3% (95%
      CI, 25.4%-27.2%) in 1998 and 25.4% (95% CI, 24.5%-26.3%) in 2008. CONCLUSIONS:
      Multiple chronic disease is increasingly prevalent among older U.S. adults,
      whereas the prevalence of impairment and disability, while substantial, remain
      stable.

PMID- 21851631
TI  - The cadaver of a Caucasian man with a supernumerary fourth dorsal interosseous
      muscle in the right hand: a case report.
AB  - INTRODUCTION: The human hand is a complex anatomic entity consisting of many
      muscles, nerves, and vessels, thus providing a special ability to perform
      accurate and meticulous movements. In this group of muscles are the four dorsal
      interosseous muscles. CASE PRESENTATION: A distinct supernumerary fourth dorsal
      interosseous muscle was found in the right hand of the cadaver of a 76-year-old
      Caucasian man without any other concomitant abnormality. CONCLUSIONS: The
      presence of such an additional muscle in the hand should be considered in the
      management of hand deformities, whether the treatment is conservative or
      surgical.

PMID- 21851632
TI  - Access to primary healthcare services for the Roma population in Serbia: a
      secondary data analysis.
AB  - BACKGROUND: Serbia has proclaimed access to healthcare as a human right. In a
      context wherein the Roma population are disadvantaged, the aim of this study was
      to assess whether the Roma population are able to effectively access primary care
      services, and if not, what barriers prevent them from doing so. The history of
      the Roma in Serbia is described in detail so as to provide a context for their
      current vulnerable position. METHODS: Disaggregated data were analyzed from three
      population groups in Serbia; the general population, the Roma population, and the
      poorest quintile of the general population not including the Roma. The effective
      coverage framework, which incorporates availability, affordability,
      accessibility, acceptability, and effectiveness of health services, was used to
      structure the secondary data analysis. Acute respiratory infection (ARI) in
      children less than five years of age was used as an example as this is the
      leading cause of death in children under 5 years old in Serbia. RESULTS: Roma
      children were significantly more likely to experience an ARI than either the
      general population or the poorest quintile of the general population, not
      including the Roma. All three population groups were equally likely to not
      receive the correct treatment regime of antibiotics. An analysis of the factors
      that affect quality of access to health services reveal that personal
      documentation is a statistically significant problem; availability of health
      services is not an issue that disproportionately affects the Roma; however the
      geographical accessibility and affordability are substantive issues that
      disproportionately affect the Roma population. Affordability of services affected
      the Roma and the poorest quintile and affordability of medications significantly
      affected all three population groups. With regards to acceptability, mothers from
      all three population groups are equally likely to recognize the importance of
      seeking treatment. CONCLUSIONS: The Roma should be assisted in applying for
      personal documentation, the geographical accessibility of clinics needs to be
      addressed, and the costs of healthcare visits and medications should be reviewed.
      Areas for improvement specific to ARI are the costs of antibiotics and the
      diagnostic accuracy of providers. A range of policy recommendations are outlined.

PMID- 21851633
TI  - SAMQA: error classification and validation of high-throughput sequenced read
      data.
AB  - BACKGROUND: The advances in high-throughput sequencing technologies and growth in
      data sizes has highlighted the need for scalable tools to perform quality
      assurance testing. These tests are necessary to ensure that data is of a minimum
      necessary standard for use in downstream analysis. In this paper we present the
      SAMQA tool to rapidly and robustly identify errors in population-scale sequence
      data. RESULTS: SAMQA has been used on samples from three separate sets of cancer
      genome data from The Cancer Genome Atlas (TCGA) project. Using technical
      standards provided by the SAM specification and biological standards defined by
      researchers, we have classified errors in these sequence data sets relative to
      individual reads within a sample. Due to an observed linearithmic speedup through
      the use of a high-performance computing (HPC) framework for the majority of
      tasks, poor quality data was identified prior to secondary analysis in
      significantly less time on the HPC framework than the same data run using
      alternative parallelization strategies on a single server. CONCLUSIONS: The SAMQA
      toolset validates a minimum set of data quality standards across whole-genome and
      exome sequences. It is tuned to run on a high-performance computational
      framework, enabling QA across hundreds gigabytes of samples regardless of
      coverage or sample type.

PMID- 21851634
TI  - Utility of a simplified ultrasound assessment to assess interstitial pulmonary
      fibrosis in connective tissue disorders--preliminary results.
AB  - INTRODUCTION: Interstitial pulmonary fibrosis (IPF) is a frequent manifestation
      in patients with connective tissue disorders (CTD). Recently the ultrasound (US)
      criterion validity for its assessment has been proposed; however, the US scoring
      systems adopted include the study of several lung intercostal spaces (LIS), which
      could be time-consuming in daily clinical practice. The aim of this study was to
      investigate the utility of a simplified US B-lines scoring system compared with
      both the US comprehensive assessment and the high-resolution computed tomography
      (HRCT) findings of IPF in CTD patients. METHODS: Thirty-six patients with a
      diagnosis of CTD were enrolled. Each patient underwent chest HRCT and lung US by
      an experienced radiologist and rheumatologist, respectively. Both comprehensive
      and simplified US B-lines assessments were scanned. The comprehensive US
      assessment was performed at 50 LIS level, whereas the simplified US assessment
      included bilaterally 14 LIS; for the anterior chest: the second LIS along the
      para-sternal lines, the fourth LIS along the mid-clavear, anterior axillary and
      mid-axillary lines; for the posterior chest: the eighth LIS along the
      paravertebral, sub-scapular and posterior axillary lines. For criterion validity,
      HRCT was considered the gold standard. Feasibility, inter and intra-observer
      reliability was also investigated. RESULTS: A highly significant correlation
      between comprehensive and simplified US assessment was found (P = 0.0001). A
      significant correlation was also found between the simplified US assessment and
      HRCT findings (P = 0.0006). Kappa values for the inter-observer simplified US
      assessment were in a range from 0.769 to 0.885, whereas the concordance
      correlation coefficient values for the intra-observer were from 0.856 to 0.955.
      There was a relevant difference in time spent on comprehensive (mean 23.3 +/- SD
      4.5 minutes) with respect to the simplified US assessment (mean 8.6 +/- SD 1.4)
      (P < 0.00001). CONCLUSIONS: Our results provide a new working hypothesis in favor
      of the utility of a simplified US B-lines assessment as an adjunct method to
      assess IPF in patients with CTD.

PMID- 21851635
TI  - SolRgene: an online database to explore disease resistance genes in tuber-bearing
      Solanum species.
AB  - BACKGROUND: The cultivated potato (Solanum tuberosum L.) is an important food
      crop, but highly susceptible to many pathogens. The major threat to potato
      production is the Irish famine pathogen Phytophthora infestans, which causes the
      devastating late blight disease. Potato breeding makes use of germplasm from wild
      relatives (wild germplasm) to introduce resistances into cultivated potato. The
      Solanum section Petota comprises tuber-bearing species that are potential donors
      of new disease resistance genes. The aim of this study was to explore Solanum
      section Petota for resistance genes and generate a widely accessible resource
      that is useful for studying and implementing disease resistance in potato.
      DESCRIPTION: The SolRgene database contains data on resistance to P. infestans
      and presence of R genes and R gene homologues in Solanum section Petota. We have
      explored Solanum section Petota for resistance to late blight in high throughput
      disease tests under various laboratory conditions and in field trials. From
      resistant wild germplasm, segregating populations were generated and assessed for
      the presence of resistance genes. All these data have been entered into the
      SolRgene database. To facilitate genetic and resistance gene evolution studies,
      phylogenetic data of the entire SolRgene collection are included, as well as a
      tool for generating phylogenetic trees of selected groups of germplasm. Data from
      resistance gene allele-mining studies are incorporated, which enables detection
      of R gene homologs in related germplasm. Using these resources, various
      resistance genes have been detected and some of these have been cloned, whereas
      others are in the cloning pipeline. All this information is stored in the online
      SolRgene database, which allows users to query resistance data, sequences,
      passport data of the accessions, and phylogenic classifications. CONCLUSION:
      Solanum section Petota forms the basis of the SolRgene database, which contains a
      collection of resistance data of an unprecedented size and precision.
      Complemented with R gene sequence data and phylogenetic tools, SolRgene can be
      considered the primary resource for information on R genes from potato and wild
      tuber-bearing relatives.

PMID- 21851636
TI  - Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of cigarette
      smoke exposure before pregnancy on diabetic rats and their offspring development.
      METHODS: Diabetes was induced by streptozotocin and cigarette smoke exposure was
      conducted by mainstream smoke generated by a mechanical smoking device and
      delivered into a chamber. Diabetic female Wistar rats were randomly distributed
      in four experimental groups (n minimum = 13/group): nondiabetic (ND) and diabetic
      rats exposed to filtered air (D), diabetic rats exposed to cigarette smoke prior
      to and into the pregnancy period (DS) and diabetic rats exposed to cigarette
      smoke prior to pregnancy period (DSPP). At day 21 of pregnancy, rats were killed
      for maternal biochemical determination and reproductive outcomes. RESULTS: The
      association of diabetes and cigarette smoke in DSPP group caused altered glycemia
      at term, reduced number of implantation and live fetuses, decreased litter and
      maternal weight, increased pre and postimplantation loss rates, reduced
      triglyceride and VLDL-c concentrations, increased levels of thiol groups and MDA.
      Besides, these dams presented increased SOD and GSH-Px activities. However, the
      increased antioxidant status was not sufficient to prevent the lipid peroxidation
      observed in these animals. CONCLUSION: Despite the benefits stemming from smoking
      interruption during the pregnancy of diabetic rats, such improvement was
      insufficient to avoid metabolic alterations and provide an adequate intrauterine
      environment for embryofetal development. Therefore, these results suggest that it
      is necessary to cease smoking extensive time before planning pregnancy, since
      stopping smoking only when pregnancy is detected may not contribute effectively
      to fully adequate embryofetal development.

PMID- 21851637
TI  - Affinity-based enrichment strategies to assay methyl-CpG binding activity and DNA
      methylation in early Xenopus embryos.
AB  - BACKGROUND: DNA methylation is a widespread epigenetic modification in vertebrate
      genomes. Genomic sites of DNA methylation can be bound by methyl-CpG-binding
      domain proteins (MBDs) and specific zinc finger proteins, which can recruit co
      repressor complexes to silence transcription on targeted loci. The binding to
      methylated DNA may be regulated by post-translational MBD modifications.
      FINDINGS: A methylated DNA affinity precipitation method was implemented to assay
      binding of proteins to methylated DNA. Endogenous MeCP2 and MBD3 were
      precipitated from Xenopus oocyte extracts and conditions for methylation-specific
      binding were optimized. For a reverse experiment, DNA methylation in early
      Xenopus embryos was assessed by MBD affinity capture. CONCLUSIONS: A methylated
      DNA affinity resin can be applied to probe for MBD activity in extracts. This
      assay has a broad application potential as it can be coupled to downstream
      procedures such as western blotting, fluorimetric HDAC assays and quantitative
      mass spectrometry. Methylated DNA affinity capture by methyl-CpG binding proteins
      produces fractions highly enriched for methylated DNA, suitable for coupling to
      next generation sequencing technologies. The two enrichment strategies allow
      probing of methyl-CpG protein interactions in early vertebrate oocytes and
      embryos.

PMID- 21851639
TI  - Selection of reference genes for quantitative real-time PCR expression studies of
      microdissected reproductive tissues in apomictic and sexual Boechera.
AB  - BACKGROUND: Apomixis, a natural form of asexual seed production in plants, is
      considered to have great biotechnological potential for agriculture. It has been
      hypothesised that de-regulation of the sexual developmental pathway could trigger
      apomictic reproduction. The genus Boechera represents an interesting model system
      for understanding apomixis, having both sexual and apomictic genotypes at the
      diploid level. Quantitative qRT-PCR is the most extensively used method for
      validating genome-wide gene expression analyses, but in order to obtain reliable
      results, suitable reference genes are necessary. In this work we have evaluated
      six potential reference genes isolated from a 454 (FLX) derived cDNA library of
      Boechera. RNA from live microdissected ovules and anthers at different
      developmental stages, as well as vegetative tissues of apomictic and sexual
      Boechera, were used to validate the candidates. RESULTS: Based on homologies with
      Arabidopsis, six genes were selected from a 454 cDNA library of Boechera: RPS18
      (Ribosomal sub protein 18), Efalpha1 (Elongation factor 1 alpha), ACT 2 (Actin2),
      UBQ (polyubiquitin), PEX4 (Peroxisomal ubiquitin conjugating enzyme) and
      At1g09770.1 (Arabidopsis thaliana cell division cycle 5). Total RNA was extracted
      from 17 different tissues, qRT-PCRs were performed, and raw Ct values were
      analyzed for primer efficiencies and gene ratios. The geNorm and normFinder
      applications were used for selecting the most stable genes among all tissues and
      specific tissue groups (ovule, anthers and vegetative tissues) in both apomictic
      and sexual plants separately. Our results show that BoechRPS18, BoechEfalpha1,
      BoechACT2 and BoechUBQ were the most stable genes. Based on geNorm, the
      combinations of BoechRPS18 and BoechEfalpha1 or BoechUBQ and BoechEfalpha1 were
      the most stable in the apomictic plant, while BoechRPS18 and BoechACT2 or
      BoechUBQ and BoechACT2 performed best in the sexual plant. When subgroups of
      tissue samples were analyzed, different optimal combinations were identified in
      sexual ovules (BoechUBQ and BoechEfalpha1), in anthers from both reproductive
      systems (BoechACT2 and BoechEfalpha1), in apomictic vegetative tissues
      (BoechEfalpha1 and BoechACT2) and sexual vegetative tissues (BoechRPS18 and
      BoechEfalpha1). NormFinder ranked BoechACT2 as the most stable in the apomictic
      plant, while BoechRPS18 was the best in the sexual plant. The subgroups analysis
      identified the best gene for both apomictic and sexual ovules (BoechRPS18), for
      anthers from both reproductive system (BoechEfalpha1) and for apomictic and
      vegetative tissues (BoechACT2 and BoechRPS18 respectively) CONCLUSIONS: From a
      total of six tested genes, BoechRPS18, BoechEfalpha1, BoechACT2 and BoechUBQ
      showed the best stability values. We furthermore provide detailed information for
      the accurate normalization of specific tissue gene expression analyses of
      apomictic and sexual Boechera.

PMID- 21851638
TI  - Transcriptome profiling of sheep granulosa cells and oocytes during early
      follicular development obtained by laser capture microdissection.
AB  - BACKGROUND: Successful achievement of early folliculogenesis is crucial for
      female reproductive function. The process is finely regulated by cell-cell
      interactions and by the coordinated expression of genes in both the oocyte and in
      granulosa cells. Despite many studies, little is known about the cell-specific
      gene expression driving early folliculogenesis. The very small size of these
      follicles and the mixture of types of follicles within the developing ovary make
      the experimental study of isolated follicular components very difficult.The
      recently developed laser capture microdissection (LCM) technique coupled with
      microarray experiments is a promising way to address the molecular profile of
      pure cell populations. However, one main challenge was to preserve the RNA
      quality during the isolation of single cells or groups of cells and also to
      obtain sufficient amounts of RNA.Using a new LCM method, we describe here the
      separate expression profiles of oocytes and follicular cells during the first
      stages of sheep folliculogenesis. RESULTS: We developed a new tissue fixation
      protocol ensuring efficient single cell capture and RNA integrity during the
      microdissection procedure. Enrichment in specific cell types was controlled by
      qRT-PCR analysis of known genes: six oocyte-specific genes (SOHLH2, MAEL, MATER,
      VASA, GDF9, BMP15) and three granulosa cell-specific genes (KL, GATA4, AMH).A
      global gene expression profile for each follicular compartment during early
      developmental stages was identified here for the first time, using a bovine
      Affymetrix chip. Most notably, the granulosa cell dataset is unique to date. The
      comparison of oocyte vs. follicular cell transcriptomes revealed 1050 transcripts
      specific to the granulosa cell and 759 specific to the oocyte.Functional analyses
      allowed the characterization of the three main cellular events involved in early
      folliculogenesis and confirmed the relevance and potential of LCM-derived RNA.
      CONCLUSIONS: The ovary is a complex mixture of different cell types. Distinct
      cell populations need therefore to be analyzed for a better understanding of
      their potential interactions. LCM and microarray analysis allowed us to identify
      novel gene expression patterns in follicular cells at different stages and in
      oocyte populations.

PMID- 21851640
TI  - Real-time PCR detection of Plasmodium directly from whole blood and filter paper
      samples.
AB  - BACKGROUND: Real-time PCR is a sensitive and specific method for the analysis of
      Plasmodium DNA. However, prior purification of genomic DNA from blood is
      necessary since PCR inhibitors and quenching of fluorophores from blood prevent
      efficient amplification and detection of PCR products. METHODS: Reagents designed
      to specifically overcome PCR inhibition and quenching of fluorescence were
      evaluated for real-time PCR amplification of Plasmodium DNA directly from blood.
      Whole blood from clinical samples and dried blood spots collected in the field in
      Colombia were tested. RESULTS: Amplification and fluorescence detection by real
      time PCR were optimal with 40* SYBR(r) Green dye and 5% blood volume in the PCR
      reaction. Plasmodium DNA was detected directly from both whole blood and dried
      blood spots from clinical samples. The sensitivity and specificity ranged from 93
      100% compared with PCR performed on purified Plasmodium DNA. CONCLUSIONS: The
      methodology described facilitates high-throughput testing of blood samples
      collected in the field by fluorescence-based real-time PCR. This method can be
      applied to a broad range of clinical studies with the advantages of immediate
      sample testing, lower experimental costs and time-savings.

PMID- 21851641
TI  - Oral health and social and emotional well-being in a birth cohort of Aboriginal
      Australian young adults.
AB  - BACKGROUND: Social and emotional well-being is an important component of overall
      health. In the Indigenous Australian context, risk indicators of poor social and
      emotional well-being include social determinants such as poor education,
      employment, income and housing as well as substance use, racial discrimination
      and cultural knowledge. This study sought to investigate associations between
      oral health-related factors and social and emotional well-being in a birth cohort
      of young Aboriginal adults residing in the northern region of Australia's
      Northern Territory. METHODS: Data were collected on five validated domains of
      social and emotional well-being: anxiety, resilience, depression, suicide and
      overall mental health. Independent variables included socio-demographics, dental
      health behaviour, dental disease experience, oral health-related quality of life,
      substance use, racial discrimination and cultural knowledge. RESULTS: After
      adjusting for other covariates, poor oral health-related items were associated
      with each of the social and emotional well-being domains. Specifically, anxiety
      was associated with being female, having one or more decayed teeth and racial
      discrimination. Resilience was associated with being male, having a job, owning a
      toothbrush, having one or more filled teeth and knowing a lot about Indigenous
      culture; while being female, having experienced dental pain in the past year, use
      of alcohol, use of marijuana and racial discrimination were associated with
      depression. Suicide was associated with being female, having experience of
      untreated dental decay and racial discrimination; while being female, having
      experience of dental disease in one or more teeth, being dissatisfied about
      dental appearance and racial discrimination were associated with poor mental
      health. CONCLUSION: The results suggest there may be value in including oral
      health-related initiatives when exploring the role of physical conditions on
      Indigenous social and emotional well-being.

PMID- 21851643
TI  - Study protocol: a pragmatic randomised controlled trial of a 12-week physical
      activity and nutritional education program for overweight Aboriginal and Torres
      Strait Islander women.
AB  - BACKGROUND: Aboriginal and Torres Strait Islander women have a higher prevalence
      and incidence of obesity and type 2 diabetes than non-Indigenous Australian
      women. Physical inactivity is a key modifiable risk factor for obesity and
      evidence shows that even modest reductions in waist circumference (WC) have
      significant health benefits. Trialing physical activity programs in difficult-to
      reach high risk groups, especially urban Indigenous Australians poses distinct
      implementation challenges. METHODS/DESIGN: The trial objective is to evaluate the
      effectiveness of a structured 12-week physical activity group program with
      nutritional advice. The design is a pragmatic randomised controlled trial. This
      study protocol describes the implementation and evaluation of the program.
      Participants are randomised into either an intervention or waitlisted group. The
      waitlisted group have a 12 month waiting period before commencing the 12-week
      program. Participant data is collected at baseline, 12, 24 and 52 weeks.
      Participants are Aboriginal and Torres Strait Islander women, aged 18-64 years
      with a waist circumference greater than 80 centimetres residing in Adelaide. The
      primary outcome measure is WC change immediately post program from baseline.
      Secondary outcomes include short term and long term changes in WC, weight, blood
      pressure, fasting blood glucose, insulin, insulin resistance (calculated HOMA),
      haemoglobin A1C (HbA1C), triglycerides and C-reactive protein (CRP). Behavioural
      and psychosocial surveys are administered to assess physical activity, dietary
      intake and the participant's motivation, self-efficacy and perceived social
      support for physical activity. Qualitative interviews focusing on participants'
      motivation, enablers and barriers to healthy eating and physical activity will be
      undertaken. Implementation fidelity and participation are also assessed.
      DISCUSSION: The Aboriginal and Torres Strait Islander Women's Fitness Program
      (WFP) is designed to provide a rigorous physiological and client-based evaluation
      of a structured 12-week program aimed to increase metabolic fitness and reduce WC
      in this high risk population. Evaluation results aim to provide the support
      necessary to design programs that are accessible, affordable and effective at
      reducing WC, while also improving the metabolic profile of overweight Aboriginal
      and Torres Strait Islander women. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry ACTRN12610000224022.

PMID- 21851642
TI  - Comparative efficacy and safety of the fixed versus unfixed combination of
      latanoprost and timolol in Chinese patients with open-angle glaucoma or ocular
      hypertension.
AB  - BACKGROUND: A noninferiority trial was conducted to evaluate the efficacy of a
      single evening dose of fixed-combination latanoprost 50 MUg/mL and timolol 0.5
      mg/mL (Xalacom(r); LTFC), in Chinese patients with primary open-angle glaucoma
      (POAG) or ocular hypertension (OH) who were insufficiently controlled on beta
      blocker monotherapy or beta-blocker-based dual therapy. METHODS: This 8-week,
      randomized, open-label, parallel-group, noninferiority study compared once-daily
      evening dosing of LTFC with the unfixed combination of latanoprost, one drop in
      the evening, and timolol, one drop in the morning (LTuFC). The primary efficacy
      endpoint was the mean change from baseline to week 8 in diurnal intraocular
      pressure (IOP; mean of 8 AM, 10 AM, 2 PM, 4 PM IOPs). LTFC was considered
      noninferior to LTuFC if the upper limit of the 95% confidence interval (CI) of
      the difference was < 1.5 mmHg (analysis of covariance). RESULTS: Baseline
      characteristics were similar for LTFC (N = 125; POAG, 70%; mean IOP, 25.8 mmHg)
      and LTuFC (N = 125; POAG, 69%; mean IOP, 26.0 mmHg). Mean diurnal IOP changes
      from baseline to week 8 were -8.6 mmHg with LTFC and -8.9 mmHg with LTuFC
      (between-treatment difference: 0.3 mmHg; 95%-CI, -0.3 to 1.0). Both treatments
      were well tolerated. CONCLUSIONS: A single evening dose of LTFC was at least as
      effective as the unfixed combination of latanoprost in the PM and timolol in the
      AM in reducing IOP in Chinese subjects with POAG or OH whose IOP was
      insufficiently reduced with beta-blocker monotherapy or beta-blocker-based dual
      therapy. LTFC is an effective and well tolerated once-daily treatment for POAG
      and OH.

PMID- 21851644
TI  - The balance between intrahepatic IL-17(+) T cells and Foxp3(+) regulatory T cells
      plays an important role in HBV-related end-stage liver disease.
AB  - BACKGROUND: IL-17(+) T helper cells and Foxp3(+) regulatory T cells are CD4(+) T
      helper cells with reciprocally regulated differentiation and function. Their
      frequency and function vary in patients with chronic hepatitis B. In this study,
      we investigated the balance between IL-17(+) T cells and Foxp3(+) regulatory T
      cells and illustrated their function in the aggravation of chronic hepatitis B
      (CHB). RESULTS: Twenty-six patients with chronic HBV -related liver failure
      (CLF), thirty-one patients with acute on chronic HBV-related liver failure (ACLF)
      and twelve normal controls were enrolled in our study. The expressions of IL-17,
      Foxp3, CD4, CD8 and perforin in liver tissue were measured by immunochemistry for
      the evaluation of liver-infiltrating lymphocytes. The frequency of liver IL-17(+)
      T cells on liver inflammatory cells and their proportion in the total CD4(+) T
      cell population increased markedly in the ACLF group, while the frquency of
      Foxp3+ T cells and their proportion in the total CD4(+) T cell population did not
      show a significant difference in the two HBV infection groups. In addition, the
      ACLF group showed a dramatically higher IL-17(+) /Foxp3(+) ratio than the CLF
      group. CD4(+) T cells increased significantly in the liver of patients with ACLF,
      compared with those in the liver of patients with CLF. CONCLUSIONS: Our findings
      suggest that intrahepatic IL-17(+) T cells play an important role in the
      development of chronic HBV and that the imbalance between IL-17(+) and Foxp3(+) T
      cells in the liver may lead to progression of the disease but the mechanism
      should be further explored.

PMID- 21851645
TI  - Bioactivities of major constituents isolated from Angelica sinensis (Danggui).
AB  - Danggui, also known as Angelica sinensis (Oliv.) Diels (Apiaceae), has been used
      in Chinese medicine to treat menstrual disorders. Over 70 compounds have been
      isolated and identified from Danggui. The main chemical constituents of Angelica
      roots include ferulic acid, Z-ligustilide, butylidenephthalide and various
      polysaccharides. Among these compounds, ferulic acid exhibits many bioactivities
      especially anti-inflammatory and immunostimulatory effects; Z-ligustilide exerts
      anti-inflammatory, anti-cancer, neuroprotective and anti-hepatotoxic effects; n
      butylidenephthalide exerts anti-inflammatory, anti-cancer and anti-cardiovascular
      effects.

PMID- 21851647
TI  - Novel antiviral activity of neuraminidase inhibitors against an avian influenza a
      virus.
AB  - BACKGROUND: Neuraminidase (NA) inhibitors used for influenza therapy are believed
      to prevent the release of progeny virus from the surface of an infected cell. In
      this study, we found that NA inhibitors have a novel antiviral function against
      an avian influenza virus. RESULTS: Madin-Darby canine kidney cells, commonly used
      for the isolation and propagation of the influenza virus, were infected with an
      avian influenza viral strain A/chicken/German/N/49(H10N7) (H10/chicken) or a
      human influenza viral strain A/Osaka/981/98(H3N2) (H3/Osaka) virus. Cells were
      incubated in a medium without or with a NA inhibitor, oseltamivir carboxylate
      (GS4071), from 1 to 13 h post infection (p.i.). Infected cells were washed 12 h
      p.i. to remove GS4071, incubated for 1 h without GS4071, and assayed for virus
      production. Incubation with GS4071 decreased the production of infectious
      viruses. When H10/chicken virus-infected cells were incubated with GS4071 from 12
      to 13 h p.i. (i.e., 1 h before the virus production assay), the inhibitory effect
      was clearly observed, however, the same was not evident for H3/Osaka virus
      infected cells. Furthermore, viral protein synthesis in infected cells was not
      affected by GS4071. Using a scanning electron microscope, many single spherical
      buds were observed on the surface of H3/Osaka virus-infected cells incubated
      without GS4071, whereas many aggregated particles were observed on the surface of
      cells incubated with GS4071. However, many long tubular virus-like structures,
      with no aggregated particles, were observed on the surface of H10/chicken virus
      infected cells incubated with GS4071. The same results were obtained when another
      NA inhibitor, zanamivir, was used. CONCLUSIONS: These results indicate that NA
      inhibitors interfered with virus particle formation in the H10/chicken virus
      infected cells, in which the inhibitor caused the formation of long tubular virus
      like structures instead of spherical virus particles.

PMID- 21851646
TI  - Biomarkers in T cell therapy clinical trials.
AB  - T cell therapy represents an emerging and promising modality for the treatment of
      both infectious disease and cancer. Data from recent clinical trials have
      highlighted the potential for this therapeutic modality to effect potent anti
      tumor activity. Biomarkers, operationally defined as biological parameters
      measured from patients that provide information about treatment impact, play a
      central role in the development of novel therapeutic agents. In the absence of
      information about primary clinical endpoints, biomarkers can provide critical
      insights that allow investigators to guide the clinical development of the
      candidate product. In the context of cell therapy trials, the definition of
      biomarkers can be extended to include a description of parameters of the cell
      product that are important for product bioactivity. This review will focus on
      biomarker studies as they relate to T cell therapy trials, and more specifically:
      i. An overview and description of categories and classes of biomarkers that are
      specifically relevant to T cell therapy trials, and ii. Insights into future
      directions and challenges for the appropriate development of biomarkers to
      evaluate both product bioactivity and treatment efficacy of T cell therapy
      trials.

PMID- 21851648
TI  - Characterization of barley (Hordeum vulgare L.) NAC transcription factors
      suggests conserved functions compared to both monocots and dicots.
AB  - BACKGROUND: The NAC transcription factor family is involved in the regulation of
      traits in both monocots and dicots of high agronomic importance. Understanding
      the precise functions of the NAC genes can be of utmost importance for the
      improvement of cereal crop plants through plant breeding. For the cereal crop
      plant barley (Hordeum vulgare L.) only a few NAC genes have so far been
      investigated. RESULTS: Through searches in publicly available barley sequence
      databases we have obtained a list of 48 barley NAC genes (HvNACs) with 43 of them
      representing full-length coding sequences. Phylogenetic comparisons to
      Brachypodium, rice, and Arabidopsis NAC proteins indicate that the barley NAC
      family includes members from all of the eight NAC subfamilies, although by
      comparison to these species a number of HvNACs still remains to be identified.
      Using qRT-PCR we investigated the expression profiles of 46 HvNACs across eight
      barley tissues (young flag leaf, senescing flag leaf, young ear, old ear, milk
      grain, late dough grain, roots, and developing stem) and two hormone treatments
      (abscisic acid and methyl jasmonate). CONCLUSIONS: Comparisons of expression
      profiles of selected barley NAC genes with the published functions of closely
      related NAC genes from other plant species, including both monocots and dicots,
      suggest conserved functions in the areas of secondary cell wall biosynthesis,
      leaf senescence, root development, seed development, and hormone regulated stress
      responses.

PMID- 21851649
TI  - Generation of an infectious clone of HuN4-F112, an attenuated live vaccine strain
      of porcine reproductive and respiratory syndrome virus.
AB  - BACKGROUND: Nowadays, PRRS has become one of the most economically important
      infectious diseases of pig worldwide. To better characterize and understand the
      molecular basis of PRRSV virulence determinants, it would be important to develop
      the infectious cDNA clones. In this regard, HuN4-F112, a live-attenuated North
      American-type PRRSV vaccine strain, could serve as an excellent model. RESULTS:
      In the study, genomic sequence of HuN4-F112, an attenuated vaccine virus derived
      from the highly pathogenic porcine reproductive and respiratory syndrome virus
      (PRRSV) HuN4 strain, was determined and its full-length cDNA was cloned. Capped
      RNA was transcribed in vitro from the cDNA clone and transfected into BHK-21
      cells. The supernatant from transfected monolayers were serially passaged in Marc
      145 cells. The rescued virus exhibited a similar growth pattern to its parental
      virus in Marc-145 cells with peak titers at 48 h post-infection. CONCLUSION: In
      conclusion, we rescued virus from an infectious cDNA clone of attenuated vaccine.
      It is possible in the future that a new attenuated PRRSV vaccine with broader
      specificity and good immunogenicity can be designed in vitro via an infectious
      cDNA clone platform coupled with validated information on virulence determinants.

PMID- 21851651
TI  - Tetanus in the dog: review and a case-report of concurrent tetanus with hiatal
      hernia.
AB  - : Tetanus with hiatal hernia was diagnosed in a four-month-old female sheepdog
      pup. The animal was treated with tetanus antitoxin, antibiotics, fluids and
      intensive nursing care for three weeks and subsequently made a full recovery.

PMID- 21851652
TI  - Surgical management of 43 cases of chronic otitis externa in the dog.
AB  - : Over a seven-year period, chronic otitis externa was surgically managed in 43
      dogs at the University Veterinary Hospital of University College Dublin. Lateral
      ear canal resection (LECR) was undertaken in nine of the 43 dogs: results were
      unsatisfactory, with a failure of the surgery in five of eight dogs and one dog
      lost to follow-up. Once end-stage otitis externa, with or without otitis media,
      is diagnosed, total ear canal ablation and lateral bulla osteotomy (TECA/LBO) is
      the best treatment option. In this series, 37 of 43 dogs underwent TECA/LBO and
      of the 29 dogs for which follow-up results were obtained 27 (93%) had an
      excellent or improved outcome to surgery. Complications following all procedures
      were most common in cases with a concurrent dermatopathy; therefore, definitive
      diagnosis and medical treatment for skin and ear disease is essential.

PMID- 21851653
TI  - Update on the development of a novel dry cow therapy using a bismuth-based
      intramammary teat seal in combination with the bacteriocin lacticin 3147.
AB  - : Public concerns over the widespread prophylactic use of antibiotics have led to
      a search for alternatives to dry cow therapy for the prevention of intramammary
      infections. A popular alternative is to infuse a teat seal at drying-off. The
      teat seal is a viscous non-antibiotic formulation and when it is infused into the
      teat canal and the teat sinus it forms an internal seal that provides a physical
      barrier to invasion by mastitis-causing pathogens. Enhancement of teat seal
      formulations may be achieved using non-antibiotic additives such as bacteriocins,
      potent proteins produced by some bacteria that have the ability to kill other
      microorganisms. This paper traces the history of investigations at Moorepark
      Research Centre into the efficacy of teat seal plus lacticin 3147, a bacteriocin
      produced by Lactococcus lactis DPC3147, in the prevention of intramammary
      infections in dry cows. Indications from on-going investigations are that a dry
      cow formulation combining the two products has considerable potential as a non
      antibiotic prophylactic product.

PMID- 21851654
TI  - Perinatal asphyxia syndrome in the foal: review and a case report.
AB  - : This report presented a brief overview of the literature on the perinatal
      asphyxia syndrome (PAS) in foals as a prelude to a description of the
      investigation and treatment of acute onset seizures in a 24-hour-old Thoroughbred
      colt foal.PAS can cause a wide variety of clinical abnormalities, of which
      seizures due to encephalopathy are the most significant. The structural and
      biochemical components of CNS neurones are disrupted by the shift from oxidative
      to anaerobic metabolism, with a resultant deficit in cellular energy. The cells
      succumb to the combined effects of acidosis, neurotoxic activities of glutamate,
      nitric oxide and free radicals, lipid peroxidation, accumulation of intracellular
      calcium and destructive overactivity of intracellular enzymes. Concurrently, the
      hypoxia affects other organ systems and management of foals presenting with CNS
      signs requires the veterinarian to undertake a thorough clinical examination and
      to institute appropriate therapy for the various derangements induced by the
      hypoxic-ischaemic episode. Diazepam (0.1 to 0.2 mg/kg bwt) can be used for short
      term control of seizures; phenobarbital (2 to 10 mg/kg bwt) may be required for
      more prolonged treatment of recurrent seizures. The needs of the affected foal
      for nutrients, fluids and electrolytes, antimicrobial therapy and ancillary
      therapies were discussed in the literature review and illustrated in the case
      report.

PMID- 21851655
TI  - Clinical signs, diagnosis and treatment of three dogs with angiostrongylosis in
      Ireland.
AB  - : Infection with Angiostrongylus vasorum was diagnosed at necropsy on a dog that
      died from acute pulmonary haemorrhage, and on recovery of L1 larvae by Baermann
      examination of faeces from two dogs, one of which had abdominal pain and
      retroperitoneal haemorrhage, while the other had right-sided heart failure due to
      cor pulmonale. The presenting signs included syncope (one dog), exercise
      intolerance (two dogs), cough (two dogs), abdominal pain (one dog) and depression
      (one dog). One-stage prothrombin time and activated partial thromboplastin time
      were prolonged in two dogs, buccal mucosal bleeding time was prolonged in one dog
      and globulin was elevated in all three dogs. Two dogs were treated with
      fenbendazole and recovered.

PMID- 21851656
TI  - Temporal trends in reproductive performance in Irish dairy herds and associated
      risk factors.
AB  - : Irish dairy herd fertility has been declining since the 1980s. The extent,
      nature and causes of this decline in fertility and the current status of Irish
      dairy herd fertility were described. An increase in calving interval of
      approximately one day per year has been recorded. The principal components of
      this trend have been an increased incidence of postpartum endocrinopathies,
      reduced expression of oestrus and a fall in conception rate. Both submission rate
      and calving-to-service interval have increased slightly over time. Significant
      risk factors associated with these trends have been strain substitution within
      the Holstein-Friesian breed and single trait selection for milk production.
      Critically, these changes have been reflected in loss of body condition.
      Contributory factors included increased herd size and possibly increased use of
      DIYAI. The most recent Irish study showed that 48% of cows conceived to first
      service and 14% of cows were not pregnant at the end of the industry-average 15
      week spring breeding season. However, the top quartile of herds achieved a first
      service conception rate of 59%, illustrating the wide variation between herds.
      These phenotypic trends were attributed to both genetic and environmental factors
      and their interactions. Recent Irish dairy herd fertility performance falls short
      of the targets set for seasonal compact calving.

PMID- 21851657
TI  - Prevalence of antibodies to Leptospira interrogans serovar hardjo in bulk tank
      milk from unvaccinated irish dairy herds.
AB  - : Bulk tank milk samples, collected from 347 herds throughout the Republic of
      Ireland using a sampling frame based on seven milk-recording organisations, were
      tested by ELISA for antibodies to Leptospira interrogans serovar hardjo. These
      herds, which had not been vaccinated against leptospirosis within the previous
      five years, were categorised according to their province, milk-recording
      organisation and size. Two-hundred-and-seventy-three herds (79%) had a positive
      ELISA titre. Both the probability of a herd being seropositive and the antibody
      level in the herd milk sample were affected by the province (P < 0.05 and P <
      0.01, respectively) and the herd size category (P < 0.05 and P < 0.01,
      respectively). Larger herds were significantly more likely to have positive
      reactions and higher mean concentrations of antibody. It was concluded that a
      high proportion of unvaccinated Irish dairy herds have been exposed to infection
      with Leptospira hardjo.

PMID- 21851658
TI  - Effect of liner design, pulsator setting, and vacuum level on bovine teat tissue
      changes and milking characteristics as measured by ultrasonography.
AB  - : Friesian-type dairy cows were milked with different machine settings to
      determine the effect of these settings on teat tissue reaction and on milking
      characteristics. Three teat-cup liner designs were used with varying upper barrel
      dimensions (wide-bore WB = 31.6 mm; narrow-bore NB = 21.0 mm; narrow-bore NB1 =
      25.0 mm). These liners were tested with alternate and simultaneous pulsation
      patterns, pulsator ratios (60:40 and 67:33) and three system vacuum levels (40,
      44 and 50 kPa). Teat tissue was measured using ultrasonography, before milking
      and directly after milking. The measurements recorded were teat canal length
      (TCL), teat diameter (TD), cistern diameter (CD) and teat wall thickness
      (TWT).Teat tissue changes were similar with a system vacuum level of either 50
      kPa (mid-level) or 40 kPa (low-level). Widening the liner upper barrel bore
      dimension from 21.0 mm (P < 0.01) or 25.0 mm (P < 0.001) to 31.6 mm increased the
      magnitude of changes in TD and TWT after machine milking. Milk yield per cow was
      significantly (P < 0.05) higher and cluster-on time was reduced (P < 0.01) with
      the WB cluster as compared to the NB1 cluster. Minimum changes in teat tissue
      parameters were achieved with system vacuum level of 40 kPa and 50 kPa using NB
      and WB clusters, respectively. Similar changes in teat tissue and milk yield per
      cow were observed with alternate and simultaneous pulsation patterns. Widening
      pulsator ratio from 60:40 to 67:33 did not have negative effects on changes in
      teat tissue and had a positive effect on milk yield and milking time. Milk liner
      design had a bigger effect on teat tissue changes and milking characteristics
      than pulsation settings.

PMID- 21851659
TI  - Extremophiles and their application to veterinary medicine.
AB  - : Extremophiles are organisms that can grow and thrive in harsh conditions, e.g.,
      extremes of temperature, pH, salinity, radiation, pressure and oxygen tension.
      Thermophilic, halophilic and radiation-resistant organisms are all microbes, some
      of which are able to withstand multiple extremes. Psychrophiles, or cold-loving
      organisms, include not only microbes, but fish that live in polar waters and
      animals that can withstand freezing. Extremophiles are structurally adapted at a
      molecular level to withstand these conditions. Thermophiles have particularly
      stable proteins and cell membranes, psychrophiles have flexible cellular proteins
      and membranes and/or antifreeze proteins, salt-resistant halophiles contain
      compatible solutes or high concentrations of inorganic ions, and acidophiles and
      alkaliphiles are able to pump ions to keep their internal pH close to neutrality.
      Their interest to veterinary medicine resides in their capacity to be pathogenic,
      and as sources of enzymes and other molecules for diagnostic and pharmaceutical
      purposes. In particular, thermostable DNA polymerases are a mainstay of PCR-based
      diagnostics.

PMID- 21851660
TI  - Dry cow therapy with a non-antibiotic intramammary teat seal - a review.
AB  - : Dry cow antibiotic therapy is used to eliminate existing intramammary
      infections and to prevent new infections in the dry period. It is implemented as
      part of a total management system known as the 'Five-Point Plan' for mastitis
      control. Recent public concerns over the widespread prophylactic use of
      antibiotics, coupled with an increasing interest in organic farming, have lead to
      a re-evaluation of the treatment of cows at drying-off. As a result, attention
      has focussed on the use of novel alternatives to antibiotic therapy at the end of
      lactation. One such therapy involves the application of a non-antibiotic bismuth
      based intramammary teat seal designed for use in cows with low cell counts at the
      end of lactation. Like the keratin plug that forms naturally in teats of cows
      that have been dried-off, teat seal forms a physical barrier to invading
      pathogens. To date, a number of independent studies have shown that teat seal is
      as effective as traditional dry cow antibiotic products in preventing the
      occurrence of new infection during the dry period in cows with somatic cell
      counts of <=200,000 cells ml-1 at drying-off. This paper reviews the efficacy of
      teat seal in preventing dry period mastitis in both conventional and organic
      dairying systems.

PMID- 21851661
TI  - Right dorsal colitis in the horse: minireview and reports on three cases in
      Ireland.
AB  - : Right dorsal colitis (RDC) is an ulcerative inflammatory bowel disorder of the
      horse that has been associated with the administration of non-steroidal anti
      inflammatory drugs (NSAIDs), particularly in horses treated when dehydrated or
      toxaemic. The acute form of RDC may result in profuse diarrhoea, severe colic,
      dehydration, endotoxic shock and even death; the chronic form may be manifest by
      mild to moderate intermittent colic, ventral oedema and weight loss with or
      without diarrhoea. The most consistent laboratory findings are anaemia,
      hypoproteinaemia, hypoalbuminaemia and hypocalcaemia. Medical management of RDC
      requires avoidance of NSAIDs, of stressful experiences and of large-volume diets.
      Specific medications such as sucralfate and metronidazole have been used to treat
      RDC in the horse. The use of dietary additions such as psyllium and corn oil has
      been mentioned in the literature.RDC has not been reported previously in Ireland
      or Britain; here we report that the condition was diagnosed in three horses in
      Ireland on the bases of a history of phenylbutazone therapy, clinical signs,
      clinical pathology and ultrasonography. In two of the three horses the diagnosis
      was confirmed by direct inspection of the affected colon at celiotomy.

PMID- 21851662
TI  - A survey of antibodies to pestivirus in sheep in the Republic of Ireland.
AB  - : Sera from 1,448 adult ewes in 91 flocks, representing all 26 counties in the
      Republic of Ireland, were examined for pestivirus antibodies using a commercially
      available ELISA which detected IgG1 antibody to border disease virus. Eighty-one
      sheep (5.6%) in 42 flocks (46.0%) were antibody-positive. Within infected flocks,
      the mean seroprevalence level was 11.4% with a range of 6.3% to 30.0%. The
      highest antibody prevalence was detected in sheep from central lowland counties
      of Ireland. Comparative neutralisation testing of 42 ELISA-positive sera detected
      geometric mean antibody titres of 136 to the NADL strain of bovine viral
      diarrhoea virus (BVDV), 92 to the Moredun strain of border disease virus and 21
      to the 137/4 strain of border disease virus. These results suggest that BVDV may
      be the major ruminant pestivirus infecting sheep in Ireland. Although there are
      high numbers of infected flocks, many sheep within such flocks remain antibody
      negative and are at risk of giving birth to lambs with congenital border disease.

PMID- 21851663
TI  - A descriptive epidemiological study of mastitis in 12 Irish dairy herds.
AB  - : Factors relating to the occurrence of mastitis were studied on 12 Irish dairy
      herds with histories of elevated somatic cell count (SCC) and/or increased
      incidence of clinical mastitis cases. Milk recording data were analysed, housing
      conditions and calving areas were examined; dry cow therapy, clinical mastitis
      records, milking technique and aspects of milking machine function were
      assessed.Herds with a ratio of less than 110 cubicles per 100 cows were more
      likely to experience environmental mastitis. Herds with inadequate calving
      facilities, where cows spent prolonged periods on straw bedding, were likely to
      acquire environmental mastitis. In the majority of the herds, the selection of
      dry cow therapy lacked adequate planning. The majority of farmers took no action
      to reduce pain experienced by cows suffering mastitis. Deficiencies in parlour
      hygiene were evident in all herds experiencing elevation in SCC.

PMID- 21851664
TI  - Clinical assessment of epidural analgesia induced by xylazine-lidocaine
      combination accompanied by xylazine sedation in calves.
AB  - : The aim of the present study was to investigate whether epidural administration
      of a xylazine-lidocaine combination accompanied by xylazine sedation would
      provide satisfactory analgesia for some surgical procedures on 10 calves admitted
      to the Department of Veterinary Surgery, University of Kafkas with perineal
      urolithiasis (n:2), rectovaginal fistula (n:1), atresia ani (n:2),
      omphalophlebitis (n:2), omphaloarteritis (n:1) and umbilical hernia
      (n:2).Following intramuscular injection of xylazine at a dose of 0.05 mg/kg for
      sedation, xylazine-lidocaine combination (0.2 mg/kg lidocaine + 0.02 mg/kg
      xylazine + 5 ml 0.9% NaCl) was administrated into the lumbosacral (L6-S1),
      sacrococcygeal (S5-Co1) or intercoccygeal (Co1-Co2) space. Heart rate,
      respiratory rate and rectal temperature were recorded prior to and during
      analgesia at 5, 10, 15, 30 and 60 minutes. Furthermore, depth and duration of
      analgesia were evaluated during surgical intervention.The study revealed that the
      combination of epidural xylazine-lidocaine with xylazine sedation was highly
      satisfactory for surgery of the lower urinary tract and the perineal region, but
      it was less so for surgery of the umbilical area.

PMID- 21851665
TI  - Tuberculosis in cattle: the results of the four-area project.
AB  - : The four-area project was undertaken to further assess the impact of badger
      removal on the control of tuberculosis in cattle herds in Ireland. It was
      conducted between 1997 and 2002 in matched removal and reference areas in four
      counties, namely Cork, Donegal, Kilkenny and Monaghan, representing a wide range
      of Irish farming environments. In the removal areas, a proactive programme of
      badger removal was conducted, on two or three occasions each year, whereas in the
      reference areas, badger removal was entirely reactive following severe outbreaks
      of tuberculosis amongst cattle. A detailed statistical analysis of this study has
      already been presented by Griffin et al. 13; this paper presents further, mainly
      descriptive, findings from the study. In total, 2,360 badgers were captured in
      the removal areas of which 450 (19.5%) were considered positive for tuberculosis
      and 258 badgers were captured in the reference areas, with 57 (26.1%) positive
      for tuberculosis. The annual incidence of confirmed herd restrictions was lower
      in the removal area compared to the reference area in every year of the study
      period in each of the four counties. These empirical findings were consistent
      with the hazard ratios found by Griffin et al. 13. Further, the effect of
      proactive badger removal on cattle tuberculosis in the four-area project and in
      the earlier east-Offaly project, as measured using the number of reactors per
      1,000 cattle tested, were very similar, providing compelling evidence of the role
      of badgers in the epidemiology of tuberculosis in Irish cattle herds. The
      validity of the four-area project was discussed in detail. Efforts to minimise
      badger-to-cattle transmission in Ireland must be undertaken in association with
      the current comprehensive control programme, which has effectively minimised
      opportunities for cattle-to-cattle transmission.

PMID- 21851666
TI  - Nasca classification of hemivertebra in five dogs.
AB  - : Five dogs, four small mixed breed and a Doberman Pinscher, presented in our
      clinic with hemivertebra. Complete physical, radiological and neurological
      examinations were done and the spinal deformities were characterized in accord
      with the Nasca classification used in human medicine. Two dogs had multiple
      hemivertebrae (round, oval or wedge-shaped: Type 3) in the thoracic region; one
      dog had an individual surplus half vertebral body (Type 1) plus a wedge-shaped
      hemivertebra (Type 2b) in the lumbar region; one dog had multiple hemivertebrae
      which were fused on one side (Type 4a) in the thoracic region; and one dog had a
      wedge-shaped hemivertebra (Type 2a) in the cervical region.

PMID- 21851667
TI  - Granulomatous meningoencephalomyelitis in dogs: A review.
AB  - : Granulomatous meningoencephalomyelitis (GME) is an inflammatory disease of the
      central nervous system in dogs that is characterised by focal or disseminated
      granulomatous lesions within the brain and/or spinal cord, non-suppurative
      meningitis and perivascular mononuclear cuffing. The aetiology of the disease
      remains unknown, although an immune-mediated cause is suspected. This article
      reviewed the typical history, clinical signs and pathology of the condition along
      with current opinions on pathogenesis. The potential differential diagnoses for
      the disease were discussed along with current treatment options.

PMID- 21851668
TI  - A two-step species-specific 16S rRNA PCR assay for the detection of Taylorella
      equigenitalis in horses.
AB  - : A two-step PCR assay was developed for the molecular detection of Taylorella
      equigenitalis, a Gram-negative genital bacterial pathogen in horses. Two specific
      oligonucleotide primers (TE16SrRNABCHf [25mer] and TE16SrRNABCHr [29mer]) were
      designed from multiple alignments of the 16S rRNA gene loci of several closely
      related taxa, including T. asinigenitalis. Subsequent enhanced surveillance of
      250 Thoroughbred animals failed to detect the presence of this organism directly
      from clinical swabs taken from the genital tract of mares and stallions. Such a
      molecular approach offers a sensitive and specific alternative to conventional
      culture techniques, and has the potential to lead to improved diagnosis and
      subsequent management of horses involved in breeding programmes.

PMID- 21851669
TI  - Pyothorax in a cat managed by intrathoracic debridement and postoperative
      ventilatory support.
AB  - : A domestic-longhair cat presented due to lethargy, dyspnoea and
      hypersalivation. Radiographic examination revealed a bilateral pleural effusion,
      which was diagnosed as pyothorax based on cytological examination.
      Ultrasonographic examination revealed extensive loculations within the thoracic
      cavity. Exploratory sternotomy, under general anaesthesia, allowed the removal of
      approximately 100 ml of purulent fluid and debridement of a partially walled-off
      abscess and necrotic material from the pleural cavity. Postoperative positive
      pressure ventilation was required due to severe respiratory depression. Intensive
      postoperative care, including intensive continuous monitoring, thoracostomy tube
      drainage and lavage of the pleural cavity and oesophagostomy tube feeding, was
      performed. Complete resolution of clinical signs had occurred by 15 days
      postoperatively. Clinical or radiographic abnormalities were not detected at a
      follow-up examination one year after surgery.

PMID- 21851670
TI  - Exotic diseases of dogs and cats at risk of importation to Ireland.
AB  - : Changes in legislation that facilitate movement of companion animals within the
      European Union will expose those animals to microbial and parasitic organisms
      currently exotic to Ireland. This paper reviewed information on the exotic
      diseases most likely to be introduced to Ireland by travelling dogs and cats:
      rabies, leishmaniosis, babesiosis, ehrlichiosis, anaplasmosis and dirofilariosis.

PMID- 21851671
TI  - Prevalence of pathogens causing subclinical mastitis in 15 dairy herds in the
      Republic of Ireland.
AB  - : Milk samples from 285 cows in 15 dairy herds were collected for bacteriological
      analysis. Cows were selected on the basis of a somatic cell count (SCC) exceeding
      200,000 cells per ml at the three most recent milk recordings prior to sampling.
      Staphylococcus aureus and Streptococcus uberis were the predominant isolates
      accounting for 21% (n = 61) and 19% (n = 53) of isolates, respectively.
      Streptococcus uberis was more frequently isolated from split-calving herds than
      from spring-calving herds and this difference was statistically significant (P <
      0.005). Herds with suboptimal housing had a significantly greater prevalence of
      S. uberis than did herds where housing was adequate (P < 0.005). The isolation
      rates for S. aureus was significantly greater in herds where parlour hygiene was
      suboptimal (P < 0.05).

PMID- 21851672
TI  - Non-accidental injury in companion animals in the Republic of Ireland.
AB  - : Non-accidental injury (NAI), animal abuse and "battered pet" syndrome are terms
      used to identify "the intentional harm of an animal". The terms include, but are
      not limited to, wilful neglect, inflicting injury, pain or distress, or malicious
      killing of an animal. Three categories of abuse are recognised: physical, sexual
      and neglect.A postal survey was conducted to determine the extent to which NAI
      was recognised by veterinary surgeons in urban, semi-rural and rural veterinary
      practices in the Republic of Ireland. The questionnaire was sent to 600
      veterinarians; completed submissions were received from 115 respondents
      (19.2%).The occurrence of NAI was acknowledged by 106 (92.2%) of the respondents
      and cases had been seen by 50 (43.3%) of them, comprised of 36.2% of urban
      veterinary surgeons from rural towns and of 82% of urban practitioners. In 59% of
      cases the client indicated the injury was non-accidental; 39 (67.2%) of the 58
      reported cases involved a single event. Signs that made veterinary surgeons
      suspicious of NAI included inconsistent history, untreated injuries, recurring
      injuries, meekness of the animal, suspicious behaviour of the owner and injuries
      consistent with abuse. The types of injuries observed included burns,
      lacerations, gunshot wounds, poisoning, injury to genitalia, bruising and
      fractures.The findings of this study are comparable with those from other
      countries. Most but not all veterinary surgeons in Ireland recognise NAI and
      animal abuse is of significant concern in rural and urban communities as
      evidenced by this survey of practising veterinary surgeons.

PMID- 21851673
TI  - Measurements of the acid-binding capacity of ingredients used in pig diets.
AB  - : Some feed ingredients bind more acid in the stomach than others and for this
      reason may be best omitted from pig starter foods if gastric acidity is to be
      promoted. The objective of this study was to measure the acid-binding capacity
      (ABC) of ingredients commonly used in pig starter foods. Ingredients were
      categorised as follows: (i) milk products (n = 6), (ii) cereals (n = 10), (iii)
      root and pulp products (n = 5), (iv) vegetable proteins (n = 11), (v) meat and
      fish meal (n = 2), (vi) medication (n = 3), (vii) amino acids (n = 4), (viii)
      minerals (n = 16), (ix) acid salts (n = 4), (x) acids (n = 10). A 0.5 g sample of
      food was suspended in 50 ml distilled de-ionised water with continuous stirring.
      This suspension was titrated with 0.1 mol/L HCl or 0.1 mol/L NaOH so that
      approximately 10 additions of titrant was required to reach pH 3.0. The pH
      readings after each addition were recorded following equilibration for three
      minutes. ABC was calculated as the amount of acid in milliequivalents (meq)
      required to lower the pH of 1 kg food to (a) pH 4.0 (ABC-4) and (b) pH 3.0 (ABC
      3). Categories of food had significantly different (P < 0.01) ABC values. Mean
      ABC-4 and ABC-3 values of the ten categories were: (i) 623 (s.d. 367.0) and 936
      (s.d. 460.2), (ii) 142 (s.d. 79.2) and 324 (s.d. 146.4), (iii) 368 (s.d. 65.3)
      and 804 (s.d. 126.7), (iv) 381 (s.d. 186.1) and 746 (s.d. 227.0), (v) 749 (s.d.
      211.6) and 1508 (s.d. 360.8), (vi) 120 (s.d. 95.6) and 261 (s.d. 163.2), (vii)
      177 (s.d. 60.7) and 1078 (s.d. 359.0), (viii) 5064 (s.d. 5525.1) and 7051 (s.d.
      5911.6), (ix) 5057 (s.d. 1336.6) and 8945 (s.d. 2654.1) and (x) -5883 (s.d.
      4220.5) and -2591 (s.d. 2245.4) meq HCl per kg, respectively. Within category,
      ABC-3 and ABC- 4 values were highly correlated: R2 values of 0.80 and greater for
      food categories i, iv, v, vi, vii and viii. The correlation between predicted and
      observed ABC values of 34 mixed diets was 0.83 for ABC-4 and 0.71 for ABC-3. It
      was concluded that complete diets with low ABC values may be formulated through
      careful selection of ingredients. The final pH to which ABC is measured should
      matter little as ABC-3 and ABC-4 are highly correlated.

PMID- 21851674
TI  - A case of hypospadias in a dog.
AB  - : This clinical case report described a three-month-old mongrel dog that had the
      urethral orifice opening 3 cm from the tip of the penis and lacked a completely
      formed preputial sheath. It was presented to the clinic with an exposed penile
      shaft that was dry. The dog had urinary incontinence that was not of neurological
      origin. It also had unilateral agenesis of the right testicle. The preputial
      sheath was successfully reconstructed. Urinary incontinence stopped soon after
      surgery, suggesting that it had been probably due to an ascending urethritis. A
      large preputial opening was left because of the location of the urethral opening.

PMID- 21851675
TI  - A serological investigation of caseous lymphadenitis in four flocks of sheep.
AB  - A double antibody sandwich ELISA developed by ID-DLO, Lelystad to detect
      Corynebacterium pseudotuberculosis infection was used on 329 sheep from four
      pedigree Suffolk flocks in which clinical cases of caseous lymphadenitis (CLA)
      had occurred. At subsequent necropsy, typical CLA lesions were seen in 133 sheep,
      and the diagnosis was confirmed on culture. Lesions were most commonly seen in
      lungs (n = 46), parotid lymph nodes (n = 44), prescapular lymph nodes (n = 38)
      and mediastinal lymph nodes (n = 31). The sensitivity of the ELISA test for
      detecting culture-positive sheep was 0.88, while the specificity of the test was
      0.55. The antibody ELISA detected 87.5 per cent of sheep that had CLA lesions
      restricted to internal organs only. It was concluded that the ELISA test has a
      valuable role in detecting sheep with both clinical and subclinical CLA.

PMID- 21851676
TI  - Risk management of paratuberculosis in dairy herds.
AB  - Risk management of paratuberculosis (Johne's disease) in a dairy herd requires an
      assessment of the likelihood of paratuberculosis occurring in the herd, the
      economic impact of paratuberculosis on the herd and an evaluation of measures
      that can be taken to reduce this likelihood and impact.The likelihood of
      paratuberculosis occurring in the herd is related to the regional herd-level
      prevalence of paratuberculosis and the herd management (e.g., introducing animals
      from other herds). The economic impact of paratuberculosis includes production
      losses due to subclinical and clinical cases, losses due to increased replacement
      of animals and costs of control measures. Furthermore, a reduction of the price
      of milk from infected herds might result from consumer concerns about the
      zoonotic potential of paratuberculosis.Measures that reduce the likelihood of
      paratuberculosis occurring in a herd and its impact include preventive management
      measures (e.g., closed herd management and an effective separation of susceptible
      young stock from adult cattle), test-and-cull schemes for known infected herds
      and quality assurance schemes for test-negative herds. Quality assurance schemes
      for test-negative herds, such as schemes for 'low-Map bulk milk' and 'Map-free'
      herds, aim at safeguarding or increasing the profitability of these herds.Keys to
      success of risk management of paratuberculosis include realistic expectations of
      the results of paratuberculosis control, quality assurance and control programmes
      that are appreciated by farmers and incentives for farmers to participate in such
      programmes.

PMID- 21851677
TI  - Lingual haemangiosarcoma in a crossbred dog.
AB  - An eight-year-old, male neutered, crossbred dog was presented for investigation
      of a lingual mass of four months duration. Oral examination revealed a 7 cm * 5
      cm soft, fluctuant mass at the caudal aspect of the tongue. Ultrasound
      examination of the mass demonstrated mixed echogenicity, with cavitations
      containing hypoechoic and anechoic regions. Lingual haemangiosarcoma was
      diagnosed on histopathological examination of multiple biopsy samples, with
      confirmation of the vascular endothelial origin of tumour cells by positive
      immunolabelling for factor VIII-related antigen.

PMID- 21851678
TI  - A case study of bovine tuberculosis in an area of County Donegal, Ireland.
AB  - A descriptive analysis, to investigate the potential risk factors that might have
      contributed to the increased incidence of bovine tuberculosis (BTB) herd
      breakdowns in the reference area of Co. Donegal during the fifth year of the four
      area project (FAP), was performed. Seventy two different herds were restricted
      for BTB during the FAP; 10 of these herds were restricted twice, resulting in a
      total of 82 BTB breakdowns. During the first four years of the FAP, the number of
      BTB herd breakdowns in the area varied from a lowest of nine to a maximum of 18
      per year, and were geographically dispersed. In the fifth year of the study a
      considerable increase in the number of BTB breakdowns (n = 32) was observed, and
      there was a spatial 'cluster' of infected herds in the eastern part of the study
      area. The increased number of BTB breakdowns during the fifth year most likely
      occurred because of the recrudescence of infection, herd-to-herd transmission
      and, to a lesser extent, purchase of infected cattle. Infected badgers remain as
      a possible but less likely source of infection, especially as an explanation for
      the cluster of infected herds. The analysis supports the hypothesis that BTB in
      herds is a problem that cannot be addressed successfully by dedicating our
      efforts to the elimination of single risk factors. Neither is it a problem that
      needs to be investigated only at the herd level, but rather at the area level,
      including groups of contiguous herds.

PMID- 21851679
TI  - Perceptions of animal physiotherapy amongst Irish veterinary surgeons.
AB  - The aim of this study was to investigate veterinary surgeons' perceptions,
      knowledge and use of animal physiotherapy in the Republic of Ireland. A
      questionnaire was developed and sent to 200 veterinary surgeons, of which 97 were
      returned. Results indicated that 77 (79%) of respondents were aware of animal
      physiotherapists. Common sources of information included veterinary colleagues,
      owners and professional journals, with physiotherapists themselves and
      undergraduate training being less commonly cited. Awareness of animal
      physiotherapy was greatest amongst those working in equine practice (chi2 = 5.7,
      df 1, p = 0.017); they were more knowledgeable about its techniques (t = 2.806,
      df 75, p = 0.006) and more likely to refer (chi2 = 48.36, df 1, p = 0.0001).
      Seventy-four respondents (96%) thought that more research was necessary to
      increase the evidence base for animal physiotherapy. If this branch of
      physiotherapy is to develop, there needs to be increased interaction and co
      operation between veterinary surgeons and chartered animal physiotherapists.

PMID- 21851680
TI  - Isolation of avian influenza virus (H9N2) from emu in China.
AB  - This is the first reported isolation of avian influenza virus (AIV) from emu in
      China. An outbreak of AIV infection occurred at an emu farm that housed 40 four
      month-old birds. Various degrees of haemorrhage were discovered in the tissues of
      affected emus. Cell degeneration and necrosis were observed microscopically.
      Electron microscopy revealed round or oval virions with a diameter of 80 nm to
      120 nm, surrounded by an envelope with spikes. The virus was classified as low
      pathogenic AIV (LPAIV), according to OIE standards. It was named
      A/Emu/HeNen/14/2004(H9N2)(Emu/HN/2004). The HA gene (1683bp) was amplified by RT
      PCR and it was compared with other animal H9N2 AIV sequences in GenBank, the US
      National Institutes of Health genetic sequence database. The results suggested
      that Emu/HN/2004 may have come from an avian influenza virus (H9N2) from Southern
      China.

PMID- 21851681
TI  - Imported disease of dogs and cats exotic to Ireland: Echinococcus multilocularis.
AB  - Changes in legislation that facilitate the movement of animals within the
      European Union may increase the risk that some microbial and parasitic organisms,
      currently exotic to Ireland, will be introduced by travelled pet animals. It is
      possible that the fox tapeworm, Echinococcus multilocularis, might be introduced
      in that manner from any of the several member states in which it is endemic. Red
      foxes are the principal definitive hosts of E. multilocularis but dogs and cats
      can also be infected. Infection in the definitive host is of little clinical
      significance, but aberrant infection of humans results in alveolar
      echinococcosis, a debilitating disease that has a high mortality rate. Humans
      acquire the organism by ingestion of Echinococcus multilocularis eggs excreted by
      definitive hosts; the larval metacestodes develop primarily in the liver, in the
      initial asymptomatic phase as small, well-encapsulated cysts. Over time, perhaps
      five to 15 years, progressive local infiltration and secondary cyst development
      at distant sites occur with resultant clinical signs. Patients with infiltrative
      liver disease present with cholestatic jaundice, epigastric pain, fatigue, weight
      loss and hepatomegaly. If left untreated, the disease can be fatal.This paper
      recounts the life cycle of the parasite, and discusses the control measures on
      which its exclusion from Ireland depend. Strict adherence to the routine worming
      of travelled dogs with praziquantel, at appropriate doses, 24 to 48 hours prior
      to entry into the country will minimise the likelihood of introduction of this
      zoonosis.

PMID- 21851682
TI  - Comparison of the arterial blood gas, arterial oxyhaemoglobin saturation and end
      tidal carbon dioxide tension during sevoflurane or isoflurane anaesthesia in
      rabbits.
AB  - The effects of sevoflurane or isoflurane on arterial blood gas, arterial
      oxyhaemoglobin saturation and end-tidal CO2 tension were monitored during
      induction and maintenance of anaesthesia in 10 premedicated New Zealand White
      (NZW) rabbits.For induction, the anaesthetic agents were delivered via a face
      mask. After induction was completed, an endotracheal tube was introduced for
      maintenance of anaesthesia for a period of 90 minutes. Changes in heart rate,
      respiratory rate, arterial blood gas, arterial oxyhaemoglobin saturation, blood
      pH and end-tidal CO2 tension were recorded. Although sevoflurane and isoflurane
      produce similar cardiopulmonary effects in premedicated rabbits, sevoflurane
      provides a smoother and faster induction because of its lower blood/gas partition
      coefficient. Thus sevoflurane is probably a more suitable agent than isoflurane
      for mask induction and maintenance. Its lower blood solubility also makes
      sevoflurane more satisfactory than isoflurane for maintenance of anaesthesia
      because it allows the anaesthetist to change the depth of anaesthesia more
      rapidly.

PMID- 21851683
TI  - Prevalence of Listeria species in camel sausages from retail markets in Aydin
      province in Turkey and RAPD analysis of Listeria monocytogenes isolates.
AB  - Samples were taken from 100 camel sausages from the different retail markets in
      Aydin province in the south-west of Turkey and they were tested for the presence
      of Listeria spp by biochemical methods. Samples were enriched using Listeria
      Enrichment Broth and they were inoculated onto Listeria Selective Agar. Listeria
      monocytogenes was isolated from nine samples (9%), Listeria innocua from 14
      samples (14%) and Listeria welshimeri from two samples(2%). A 701 bp fragment of
      listeriolysin O sequence for L. monocytogenes was amplified using specific
      primers by polymerase chain reaction (PCR) for confirmation of the
      identification. A random primer (OPA-11) was used in a random amplified
      polymorphic DNA (RAPD) assay. This detected five different band profiles amongst
      the L. monocytogenes isolates, indicating a relatively large amount of genetic
      heterogeneity amongst the nine isolates. The study has highlighted the need for
      improved strategies for food safety, in particular appropriate hygienic
      precautions to avoid contamination of sausage during the manufacturing process
      and appropriate preservation techniques during storage and transport, to prevent
      transmission of Listeria spp to consumers at home and abroad.

PMID- 21851684
TI  - A survey of Salmonella spp and Campylobacter spp in dairy goat faeces and bulk
      tank milk in the Murcia region of Spain.
AB  - This study was designed to investigate the occurrence of Salmonella spp and
      Campylobacter spp in faeces samples from 222 healthy Murciano-Granadina dairy
      goats reared on 12 farms in Spain and in samples of bulk tank milk from 11 of
      those herds. Neither Salmonella spp nor Campylobacter spp were isolated from any
      of the samples. Our results suggest that, under the management practices applied
      to this breed in Spain, Murciano-Granadina goats are not likely to be a
      significant reservoir for these food-borne pathogens.

PMID- 21851685
TI  - An Irish perspective on Cryptosporidium. Part 1.
AB  - Cryptosporidiosis, a protozoal disease which causes significant morbidity in
      humans, is one of the chief causes of diarrhoea in neonatal ruminants. Although
      the parasite poses a significant threat to public health and animal health in
      Ireland, its epidemiology on the island is only poorly understood. Environmental
      studies have shown the waterborne parasite to be widespread in some untreated
      waterbodies around Ireland. The island's hydrogeological situation, combined with
      high stocking rates of livestock and the absence of filtration from regular water
      treatment, render it vulnerable to large-scale outbreaks. This review discusses
      the parasite in the Irish context and underlines the need for a reference
      facility to provide active surveillance on the island.

PMID- 21851686
TI  - An Irish perspective on Cryptosporidium. Part 2.
AB  - Cryptosporidiosis, a protozoal disease which causes significant morbidity in
      humans, is one of the chief causes of diarrhoea in neonatal ruminants. although
      the parasite poses a significant threat to public health and animal health in
      Ireland, its epidemiology on the island is only poorly understood. Environmental
      studies have shown the waterborne parasite to be widespread in some untreated
      waterbodies around Ireland. The island's hydrogeological situation, combined with
      high stocking rates of livestock and the absence of filtration from regular water
      treatment, render it vulnerable to large-scale outbreaks. This review discusses
      the parasite in the Irish context and underlines the need for a reference
      facility to provide active surveillance on the island.

PMID- 21851688
TI  - A study of 54 cases of left displacement of the abomasum: February to July 2005.
AB  - Fifty-four cows with left displacement of the abomasum (LDA) submitted to the
      hospital facility at Riverview Veterinary Clinic from February to July 2005 were
      treated by right flank laparotomy and omentopexy. Five cows died (a survival rate
      90.7%) and one cow (1.8%) was culled due to recurrence of the LDA post
      operatively. Forty-one cows (76%) returned to good production post-operatively.
      Thirty-nine cows (72%) were pregnant six months after corrective surgery.

PMID- 21851687
TI  - Pleural mesothelioma in a nine-month-old dog.
AB  - This paper reports on an unusual case of pleural epitheloid mesothelioma in a
      nine-month-old male, mixed breed dog. The dog was presented in-extremis and, on
      post mortem examination, multiple, exophytic, frequently pedunculated, yellowish
      red, soft to firm masses ranging from 3 mm to 6 cm in diameter were diffusely
      distributed over, and attached to, the pericardial and parietal pleural surfaces.
      Microscopically, these masses consisted of round to partially polygonalshaped,
      anaplastic cells with minimal cytoplasm and hyperchromatic nuclei covering
      papillomatous projections or as part of more densely cellular masses. A
      supporting fibrovascular stroma and mitotic figures were also evident.
      Constituent tumour cells were labeled positively with antibodies against both
      vimentin and cytokeratin. In contrast, the same cells exhibited equivocal
      labeling with an antibody directed against calretinin antigen and did not label
      with antibodies against carcinoembryonic antigen (CEA) and milk fat globule
      related antigen (MFGRA). Such tumours are rare in dogs, particularly in such a
      young animal.

PMID- 21851689
TI  - Effect of restricting silage feeding prepartum on time of calving, dystocia and
      stillbirth in Holstein-Friesian cows.
AB  - A study was carried out to investigate the effect of restricting silage feeding
      on time of calving and calving performance in Holstein-Friesian cows. In the
      treatment group (n = 1,248 cows, 12 herds) silage feeding commenced in the
      evening (17:00 to 20:00 h), after a period of restricted access (2 to 10 h) while
      in the control group ad-libitum access to silage was provided over the 24 h
      period (n = 1,193 cows, 12 herds). Daytime and nighttime calvings were defined as
      calvings occurring between the hours of 06:30 and 00:29 and between 00:30 and
      06:29, respectively. Restricting access to silage resulted in less calvings at
      night compared to cows with ad-libitum access to silage (18 vs 22%, P < 0.05).
      Cows with restricted access to silage had a higher percentage of difficult
      calvings (11 vs 7%, P < 0.001) and stillbirths (7 vs 5%, P < 0.05) compared to
      cows in the control group. The percentage of calvings at night was lower (13%)
      when access to silage was restricted for 10 h compared to 2, 4 or 6 h (22, 18,
      25%, respectively) (P < 0.001). Calf sire breed, calf gender or cow parity did
      not influence time of calving. In conclusion, offering silage to pregnant
      Holstein-Friesian cows in the evening, after a period of restricted access,
      reduced the incidence of nighttime calvings, but increased the incidence of
      dystocia and stillbirth.

PMID- 21851690
TI  - Resistance studies of erythromycin and rifampin for Rhodococcus equi over a 10
      year period.
AB  - This study sought to determine whether an increase in resistance of Rhodococcus
      equi to the antibiotics rifampin and erythromycin occurred over a 10-year period.
      This was carried out by the use of E test strips for rifampin and erythromycin to
      determine the MIC (minimum inhibitory concentration) values of Rhodococcus equi
      to this combination of antibiotics.The findings of this study indicated that
      there was an increase in resistance of Rhodococcus equi to rifampin and
      erythromycin over the 10-year period. The MIC for rifampin increased from 0.081
      MUg/ml in 1996 to 0.187 MUg/ml in 2006 and from 0.258 MUg/ml for erythromycin
      during the years prior to 2000 to 0.583 MUg/ml in 2006.This finding suggests that
      there may be a problem in the treatment of Rhodococcus equi infections in foals
      in the future, particularly as the number of drugs available for treatment of
      Rhodococcus equi infection is limited because of the intracellular capabilities
      of this bacterium. Antibiotics used in its treatment have to be able to penetrate
      the polysaccharide cell wall of Rhodococcus equi as well as the alveolar
      macrophages in which the bacterium is capable of surviving.

PMID- 21851691
TI  - Tertiary hypothyroidism in a dog.
AB  - : A nine-year-old male entire Labrador was diagnosed with pituitary dependent
      hyperadrenocorticism. Following seven months of successful mitotane therapy, the
      dog presented with marked weight gain, seborrhoea and alopecia. Routine
      clinicopathological analyses revealed marked hypercholesterolaemia. Serum total
      and free thyroxine (T4) concentrations were below their respective reference
      ranges. Serum thyroid stimulating hormone (cTSH) concentration was within
      reference range. TSH and thyrotropin releasing hormone (TRH) response tests
      revealed adequate stimulation of total T4 in both, and cTSH in the latter test.
      Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with
      suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following
      four weeks of levothyroxine therapy, circulating cholesterol concentration had
      declined, weight loss had ensued and dermatological abnormalities had improved.
      Euthanasia was performed four months later due to the development of neurological
      signs. A highly infiltrative pituitary adenoma, with effacement of the overlying
      hypothalamus was identified on post mortem examination. Tertiary hypothyroidism
      has not been previously reported in dogs.

PMID- 21851693
TI  - Analysis of Canadian and Irish forage, oats and commercially available equine
      concentrate feed for pathogenic fungi and mycotoxins.
AB  - Respiratory infections, recurrent airway obstruction (RAO) and exercise induced
      pulmonary haemorrhage (EIPH) are major causes of poor performance in horses.
      Fungi and mycotoxins are now recognised as a major cause of these conditions. The
      most notable fungi are Aspergillus and Fusarium. Fungal spores can originate from
      forage, bedding and feed and, in turn, these fungal spores can produce a series
      of mycotoxins as secondary metabolites.This study set out to ascertain the degree
      of fungal and mycotoxin contamination in feed and fodder used in Irish racing
      yards over a one-year period. Weather conditions in forage producing areas were
      sampled by Met Eireann and the Canadian Meteorological Service.Fifty per cent of
      Irish hay, 37% of haylage and 13% of Canadian hay contained pathogenic fungi. Of
      the mycotoxins, T2 and zearalenone were most prominent. Twenty-one per cent of
      Irish hay and 16% of pelleted feed contained zearalenone. Forty per cent of oats
      and 54% of pelleted feed contained T2 toxins.

PMID- 21851692
TI  - A review of the renal system and diurnal variations of renal activity in
      livestock.
AB  - Kidneys are the main organs regulating water-electrolyte homeostasis in the body.
      They are responsible for maintaining the total volume of water and its
      distribution in particular water spaces, for electrolyte composition of systemic
      fluids and also for maintaining acid-base balance. These functions are performed
      by the plasma filtration process in renal glomeruli and the processes of active
      absorption and secretion in renal tubules, all adjusted to an 'activity-rest'
      rhythm. These diurnal changes are influenced by a 24-hour cycle of activity of
      hormones engaged in the regulation of renal activity. Studies on spontaneous
      rhythms of renal activity have been carried out mainly on humans and laboratory
      animals, but few studies have been carried out on livestock animals. Moreover,
      those results cover only some aspects of renal physiology. This review gives an
      overview of current knowledge concerning renal function and diurnal variations of
      some renal activity parameters in livestock, providing greater understanding of
      general chronobiological processes in mammals. Detailed knowledge of these
      rhythms is useful for clinical, practical and pharmacological purposes, as well
      as studies on their physical performance.

PMID- 21851694
TI  - An investigation into the depth of penetration of low level laser therapy through
      the equine tendon in vivo.
AB  - Low level laser therapy (LLLT) is frequently used in the treatment of wounds,
      soft tissue injury and in pain management. The exact penetration depth of LLLT in
      human tissue remains unspecified. Similar uncertainty regarding penetration depth
      arises in treating animals. This study was designed to test the hypothesis that
      transmission of LLLT in horses is increased by clipping the hair and/or by
      cleaning the area to be treated with alcohol, but is unaffected by coat colour. A
      LLLT probe (810 nm, 500 mW) was applied to the medial aspect of the superficial
      flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied
      to the lateral aspect, directly opposite the laser probe to measure the amount of
      light transmitted. Light transmission was not affected by individual horse, coat
      colour or leg. However, it was associated with leg condition (F = 4.42, p =
      0.0032). Tendons clipped dry and clipped and cleaned with alcohol, were both
      associated with greater transmission of light than the unprepared state. Use of
      alcohol without clipping was not associated with an increase in light
      transmission. These results suggest that, when applying laser to a subcutaneous
      structure in the horse, the area should be clipped and cleaned beforehand.

PMID- 21851695
TI  - A review of factors influencing litter size in Irish sows.
AB  - Many factors influence litter size. These include genetics, gilt management,
      lactation length, parity distribution, disease, stress and boar fertility. In the
      past 20 years, litter size in Irish sows has increased by only one pig. Born
      alive figures now average at 11.2 pigs per litter. In this regard, Ireland is
      falling behind our European competitors who have made significant advances over
      this time. Denmark, for example, has an average figure of 12.7 pigs born alive
      per litter and France an average of 12.5. The single area that could be improved
      immediately is sow feeding. It is important that sows are fed correctly
      throughout pregnancy. If over-fed during pregnancy, sows will have depressed
      appetite during lactation. If underfed in pregnancy, sows will be too thin at
      farrowing. The correct way to feed a pregnant sow is to match her feed allocation
      to her requirement for maintenance, body growth and growth of her developing
      foetuses. During lactation, sows should be given as much feed as they can eat to
      prevent excessive loss of body condition. Liquid-feed curves should be such that
      lactating sows are provided with a minimum mean daily feed supply of 6.2 kg. A
      small proportion of sows will eat more and this could be given as supplementary
      dry feed. Where dry feeding is practised in the farrowing house, it is difficult
      to hand-feed sows to match their appetite. Ideally ad libitum wet/dry feeders
      should be used. From weaning to service, sows should once again be fed ad
      libitum. If liquid feeding, this means giving at least 60 MJ DE (digestible
      energy) per day during this period. If dry feeding, at least 4 kg of lactation
      diet should be fed daily. The effort spent perfecting sow feeding management on
      units should yield high dividends in the form of increased pigs born alive per
      litter.

PMID- 21851696
TI  - Transrectal ultrasonographic diagnosis of jejunoileal intussusception in a cow.

PMID- 21851697
TI  - Vaginal fibrosarcoma in a cow.

PMID- 21851698
TI  - Outbreak of botulism in a dairy herd in Turkey.
AB  - In this study, the clinical findings and results of haematological and
      biochemical analyses of 26 cattle with botulism were evaluated. The most
      important clinical signs in the affected cattle included: decreased appetite,
      ataxia, difficulty to rise, loss of tongue tone, salivation and bradycardia. A
      definitive diagnosis of botulism was based on demonstration of the preformed
      toxin in ruminal and intestinal contents and feed materials including poultry
      litter, by mouse inoculation test. This study is the first confirmation, by
      direct toxin isolation, of Clostridium botulinum type C and Clostridium botulinum
      type D in cattle, in Turkey.

PMID- 21851699
TI  - Shaping our future: animal health in a global trading environment.

PMID- 21851700
TI  - Control of Mycobacterium bovis infection in two sika deer herds in Ireland.
AB  - In a number of countries, tuberculosis (due to infection with Mycobacterium
      bovis) is a significant health problem of captive deer. This paper describes
      outbreaks of bovine tuberculosis in sika deer (Cervus nippon) on two farms in
      Ireland and the methods used to control the disease. On Farm A, infection was
      first detected during 1993. The infection was eradicated using a programme of
      test and removal, in association with segregation of young animals. A second
      outbreak (also due to infection with M. bovis, but a different RFLP profile) was
      detected in 2002. In the latter outbreak, infection was particularly prevalent in
      two groups of young deer. M. bovis with the same RFLP profile was also isolated
      in a badger found dead on the farm. Control was achieved by test and removal in
      association with herd management changes. In Herd B, infection was first detected
      in 1995, and subsequently eradicated using test and removal alone. In Herd A, re
      infection remains an ongoing risk. Control rather than eradication of infection
      may more realistic in the short-to medium-term.

PMID- 21851701
TI  - Incidence of osteochondrosis (dissecans) in Dutch warmblood horses presented for
      pre-purchase examination.
AB  - Data are lacking in the literature regarding the incidence of osteochondrosis
      (dissecans) [OC(D)] in relation to lameness evaluation in Dutch Warmblood horses.
      The objective of this retrospective study was to assess the incidence of
      radiological abnormalities consistent with osteochondrosis or osteochondrosis
      dissecans in 1,231 sound Dutch Warmblood (DW) horses presented for pre-purchase
      examination. Standardised (Dutch) pre-purchase examination protocols were
      evaluated. The pre-purchase examination included a clinical, lameness and
      radiological evaluation, performed at a private equine clinic in the Netherlands.
      Radiographical examination included views of the distal (DIP) and proximal (PIP)
      interphalangeal, metacarpo- and metatarsophalangeal (MCP/MTP), tarsocrural (TC)
      and femoropatellar (FP) joints. Radiographical evidence of OC(D) was found in
      44.3% of clinically sound DW horses. In this study, 443 horses (36%, n = 1,231)
      had evidence of OCD and 102 horses (8.3%, n = 1,231) had evidence of OC on pre
      purchase radiographs. The results also indicated that the TC joints were
      significantly more likely to be affected. A considerable number of horses did not
      demonstrate any lameness, although radiographs revealed OC(D).

PMID- 21851702
TI  - Animal abuse and intimate partner violence: researching the link and its
      significance in Ireland - a veterinary perspective.
AB  - Research on domestic violence has established a substantial association between
      intimate partner abuse and the abuse of children within the home. It is only
      recently however, that researchers have demonstrated the correlation between non
      accidental injury in animals, and abuse of women by their intimate male partners.
      A growing body of evidence suggests that animal abuse can be an early indicator
      for other forms of violent behaviour. This research includes the responses of a
      sample of 23 women using refuge services in the Republic of Ireland. It
      investigates the connection between domestic violence and animal abuse, and
      ascertains if there is sufficient support service for animals and people relevant
      to domestic abuse. In the survey population, 57% of women reported witnessing one
      or more forms of abuse, or threats of abuse, of their pets. Five of which were
      reported to have resulted in the death of the pet. Eighty seven per cent of women
      felt a facility to accommodate pets would have made their decision to leave the
      family home easier. Four women disclosed that lack of such a service and concern
      for the welfare of their companion animals caused them to remain in their abusive
      relationships for longer than they felt appropriate. Nine families placed pets in
      the care of family or friends, one woman is unaware of the fate of her pet, while
      the pets of six families remained with the abusive male after his partner entered
      a refuge. The majority of women felt unable to talk to anyone about their fears
      for their pets' welfare. Many felt that there is no service which can provide
      temporary accommodation for womens' pets while they are in refuge. The results
      obtained support those found elsewhere in larger studies in the USA and UK, and
      demonstrate an association of animal abuse in households where there is reported
      domestic violence.

PMID- 21851703
TI  - The marketing of herd health and production management services on Dutch dairy
      farms: perceptions of dairy farmers and their veterinary surgeons.
AB  - A questionnaire-based survey on veterinary herd health and production management
      services was conducted on 194 specialist dairy veterinarians and 466 dairy
      farmers. The farmers were randomly selected from greater than 6,000 farmer
      clients of the surveyed veterinarians. This paper reports these survey findings
      and the findings of an earlier survey conducted among the veterinarians. The
      survey included questions on the attributes of the service itself, the
      practitioners delivering the service, reasons for participation and the expected
      future of herd health and production management services. Reasons farmers
      participated in herd health and production management programmes included; access
      to routine screening of their herd; increasing profits; and receiving regular
      veterinary advice or solutions to remedy existing problems. Advantages of
      participation named included: good management support; higher profits; structural
      solutions to problems; and being better informed. Differences between farming
      styles were observed, pointing to the different needs and goals of farming
      styles. Farmers cited high costs and the time investment required as major
      disadvantages. The proportion of farmers citing these reasons was lower than
      expected by the veterinarians. In the future, preventive healthcare will be the
      main reason of farmers to participate. Farmers who are not using the service can
      potentially be encouraged to engage the services after gaining increased insight
      into the herd health and management service structure, the planning of
      activities, the cost-benefit of the service, veterinary surgeons being more co
      operative with other farm advisors and veterinarians being more willing to pay
      attention to quality issues on the dairy farm.

PMID- 21851704
TI  - The structure and regulation of the Irish equine industries: Links to
      considerations of equine welfare.
AB  - The equine industries in Ireland are vibrant and growing. They are broadly
      classified into two sectors: Thoroughbred racing, and sports and leisure. This
      paper describes these sectors in terms of governance, education and training in
      equine welfare, and available data concerning horse numbers, identification,
      traceability and disposal. Animal welfare, and specifically equine welfare, has
      received increasing attention internationally. There is general acceptance of
      concepts such as animal needs and persons' responsibilities toward animals in
      their care, as expressed in the 'Five Freedoms'. As yet, little has been
      published on standards of equine welfare pertaining to Ireland, or on measures to
      address welfare issues here. This paper highlights the central role of horse
      identification and legal registration of ownership to safeguard the health and
      welfare of horses.

PMID- 21851705
TI  - Herd and within-herd BoHV-1 prevalence among Irish beef herds submitting bulls
      for entry to a performance testing station.
AB  - Infectious bovine rhinotracheitis (IBR), caused by bovine herpes virus 1 (BoHV
      1), may result in various clinical consequences, including severe respiratory
      disease and conjunctivitis, venereal disease and reduced reproductive performance
      and abortion. This paper presents the serosurveillance findings from an intake of
      bulls into a performance testing station in Ireland during November 2007. The
      herd and within-herd BoHV-1 prevalence in 53 Irish beef herds and the risk
      factors for infection in these herds were determined, among bulls entering a beef
      performance testing station in Ireland. BoHV-1 status was determined for 41
      herds, of which 30 (73.2%) herds were infected and the mean within-herd BoHV-1
      prevalence was 28 (+/- 20)%. Multivariate exact logistic modelling revealed
      increasing numbers of contiguous herds and decreasing percentage of males within
      the herd as significant risk factors associated with infected herds. These
      findings highlight the high prevalence of BoHV-1 infection in those Irish beef
      herds that submitted bulls to this performance testing station, and raise
      concerns regarding IBR control nationally.

PMID- 21851706
TI  - Low reproductive performance and high sow mortality in a pig breeding herd: a
      case study.
AB  - Sow performance is a key component of the productivity of commercial pig farms.
      Reproductive failure in the sow is common in pig production. For every 100 sows
      served, 89 should farrow. In absence of specific diseases such as porcine
      parvovirus, pseudo-rabies, swine fever, leptospirosis and brucellosis, management
      failures are the most important causes of loss. A syndrome associated with
      reproductive inefficiency, and post-service vaginal discharge and high sow
      mortality in a commercial pig farm is described. Pregnancy failures exceeded 20%
      and sow mortality exceeded 12% for two consecutive years. The abnormal post
      service vaginal discharge rate was 1.7% during the period of investigation.An
      investigation involving an analysis of farm records, a review of breeding
      management practices, clinical examinations, laboratory analysis and examination
      of urogenital organs was conducted.The main contributing factors found were a sub
      optimal gilt breeding management, an inadequate culling policy in combination
      with a sub-optimal culling rate and the presence of cystitis in more than 1% of
      the urogenital organs examined. The high sow mortality rate was related to an
      aged breeding herd.A control programme was recommended based on management
      changes involving oestrus detection, movement of gilts post-service, hygiene in
      the service area, boar exposure post-service and urinary acidification. This
      programme failed to increase the farrowing rate due to incomplete implementation
      of the recommendations made. The farrowing rate increased to 86.5% subsequent to
      a farm manager change in January 2005, which resulted in complete implementation
      of the control programme.

PMID- 21851707
TI  - Analysis of factors influencing prognosis in foals with septic arthritis.
AB  - The purpose of this paper was to identify factors that would positively or
      negatively affect the short-term survival rate of foals with septic arthritis.
      Medical records of 81 foals (<=seven months of age) with a clinical diagnosis of
      septic arthritis, referred to the equine hospital at Cornell University Hospital
      for Animals, between 1994 and 2003 were reviewed. Signalment, age at
      presentation, number of affected joints, joint fluid parameters, bacterial
      agents, treatment modalities and year of treatment were compared between
      survivors and nonsurvivors. Sixty-two of 81 foals (77%) were discharged from the
      hospital and classified as 'survivors'. Multiple joint involvement and detection
      of intra-articular Gram-negative, mixed bacterial infection and degenerate
      neutrophils were negatively associated with short-term survival. Initiation of
      treatment within 24 hrs of onset of clinical signs and combination of treatment
      modalities were positively correlated with survival. Further investigation is
      needed to determine if these two factors have a similar influence on athletic
      performance.

PMID- 21851708
TI  - A case for increased private sector involvement in Ireland's national animal
      health services.
AB  - Non-regulatory animal health issues, such as Johne's disease, infectious bovine
      rhinotracheitis (IBR) and mastitis will become increasing important, with ongoing
      globalisation of markets in animals and animal products. In response, Ireland may
      need to broaden the scope of its national animal health services. However, there
      have been concerns about the respective roles and responsibilities (both
      financial and otherwise) of government and industry in any such moves. This paper
      argues the case for increased private sector involvement in Ireland's national
      animal health services, based both on theoretical considerations and country case
      studies (the Netherlands and Australia). The Dutch and Australian case studies
      present examples of successful partnerships between government and industry,
      including systems and processes to address non-regulatory animal health issues.
      In each case, the roles and responsibilities of government are clear, as are the
      principles underpinning government involvement. Furthermore, the roles and
      responsibilities (financial and otherwise) of the Dutch and Australian industry
      are determined through enabling legislation, providing both legitimacy and
      accountability. There are constraints on the use of EU and national government
      funds to support non-regulatory animal health services in EU member states (such
      as Ireland and the Netherlands).

PMID- 21851709
TI  - Equine post-breeding endometritis: A review.
AB  - The deposition of semen, bacteria and debris in the uterus of the mare after
      breeding normally induces a self-limiting endometritis. The resultant fluid and
      inflammatory products are cleared by 48 hours post cover. Mares that are
      susceptible to persistent post-breeding endometritis (PPBEM) have impaired
      uterine defence and clearance mechanisms, making them unable to resolve this
      inflammation within the normal time. This persists beyond 48 hours post-breeding
      and causes persistent fluid accumulation within the uterus. Mares with PPBEM have
      an increased rate of embryonic loss and a lower overall pregnancy rate than those
      without the condition. To enhance conception rates, mares at high risk need
      optimal breeding management as well as early diagnosis, followed by the most
      appropriate treatment. This article reviews the pathogenesis, diagnosis and
      treatment of PPBEM and the management of affected mares.

PMID- 21851710
TI  - Right cranial lung lobe torsion after a diaphragmatic rupture repair in a Jack
      Russell terrier.
AB  - A seven-year-old male Jack Russell terrier was presented with a history of
      coughing, generalised weakness and lethargy 10 days after an abdominal coeliotomy
      to repair a large diaphragmatic rupture. Thoracic radiographs demonstrated a soft
      tissue mass in the midcaudal right thoracic cavity. Ultrasonographic studies,
      bronchoscopy and subsequent exploratory thoracotomy confirmed a diagnosis of a
      right cranial lung lobe torsion (LLT), with an anomalous caudodorsal displacement
      of the affected lobe. LLT should be considered as a differential diagnosis for
      respiratory tract disease following diaphragmatic rupture repair.

PMID- 21851711
TI  - Occupational stress, work-home interference and burnout among Belgian veterinary
      practitioners.
AB  - There have been few formal studies on stress in veterinary surgeons and, in the
      rare studies available, stress is not examined jointly through the levels of job
      strain and job engagement, the sources of stress in the issue of work environment
      and the work-home interference. The authors' goal in this study was to analyse
      job engagement, job strain, burnout, work-home interference and job stress
      factors among 216 Belgian veterinary surgeons. Rural practice was compared to
      small animal and mixed activity. The mean job strain and job engagement level in
      veterinary surgeons was not higher than what we found in other working
      populations. However, 15.6% of the group were found to be suffering from high
      burnout. Rural practitioners had a lower level of job engagement than small
      animal veterinary surgeons. These small animal practitioners had a lower level of
      job strain than the mixed practitioners. The level of burnout did not differ
      significantly across the three types of activity. In comparison to other Belgian
      and Dutch workers, veterinary surgeons perceived more negative work-home
      interference. Bovine and mixed practitioners were the most concerned with this
      problem. The two most important sources of stress reported by bovine
      practitioners were relations to farmers and working time management (including
      emergencies and availability).

PMID- 21851712
TI  - Conservative treatment of a comminuted cervical fracture in a racehorse.
AB  - The 'classical' or 'Hangman' neck fracture involves the odontoid peg (process) of
      the second cervical vertebra (C2), and is described as an axial, dens or odontoid
      peg fracture in both the veterinary and human literature. Possible surgical
      treatment in both foals and adult horses requires a technique that allows
      decompression, anatomical alignment and stabilisation of the odontoid fracture. A
      limited number of surgical cases in foals have been reported in literature, but
      never in an adult horse. A mature Irish Thoroughbred racehorse was diagnosed with
      a type 2a odontoid peg fracture. Clinical signs included reluctance to move the
      head and neck, a left hind limb lameness and a neurological status of grade 2.
      The horse was treated conservatively and raced successfully five months after the
      diagnosed injury.

PMID- 21851713
TI  - Ascending placentitis in the mare: A review.
AB  - Ascending placentitis is a condition that occurs late in pregnancy when bacteria
      enter the sterile uterus from the lower reproductive tract. It leads to abortion
      or the birth of premature and weakened foals. Early detection and treatment of
      this condition is vital for ensuring the production of a viable foal.Mares with
      ascending placentitis often present in late term pregnancy with signs of
      premature udder development and premature lactation. There may be a vulvar
      discharge. Early detection of placental problems is possible using trans
      abdominal or trans-rectal ultrasonography. Hormones such as progesterone and
      relaxin may be measured as indicators of foetal stress and placental failure.
      Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate.
      The region most affected is the cervical star. Definitive diagnosis of ascending
      placentitis is by histopathological examination of the chorioallantoic
      membrane.Ideal treatment strategies are aimed at curing the infection and
      prolonging the pregnancy to as close to term as possible and consist of anti
      microbials, anti-inflammatories and hormonal support.Swabs are taken from
      affected mares to determine antibiotic sensitivity and to aid in treatment of
      foals born from these mares which are at risk of becoming septic. If detected
      early enough, the chances of producing a viable foal are greatly increased.

PMID- 21851714
TI  - Breeding soundness evaluation of bulls by semen analysis, testicular fine needle
      aspiration cytology and trans-scrotal ultrasonography.
AB  - The aim of this study was to evaluate the usefulness of trans-scrotal
      ultrasonography and testicular fine needle aspiration cytology in assessing bulls
      for breeding suitability. These two techniques were also compared with semen
      analysis. Bulls presented for breeding soundness evaluation were assessed using
      all three techniques. The findings of each technique were compared. There was
      agreement in classification of fertile bulls using all three techniques,
      suggesting that the combined use of these techniques enhances routine breeding
      soundness examination. Use of the three techniques also enhances detailed
      investigation of suspected sub-fertile bulls while accurately identifying
      testicular cause(s) of sire sub-fertility.

PMID- 21851715
TI  - Anaesthesia for the geriatric dog and cat.

PMID- 21851716
TI  - Congenital oesophageal hiatal hernia in a pug.
AB  - Congenital sliding, oesophageal or type I hiatal hernia was diagnosed in a five
      month-old pug puppy presented for evaluation of dyspnoea post feeding. The
      diagnosis was confirmed using plain film radiography. Surgical reduction of the
      hernia followed by plication of the oesophageal hiatus, oesophagopexy and left
      flank gastropexy permitted restoration of normal function. At 12 months of age,
      the dog was asymptomatic. This article describes the diagnosis and treatment of a
      congenital type 1 oesophageal hiatal herniation with unusual clinical
      presentation.

PMID- 21851717
TI  - Trends in cow numbers and culling rate in the Irish cattle population, 2003 to
      2006.
AB  - Cows are the main economic production units of Ireland's cattle industry.
      Therefore, demographic information, including overall numbers and survival rates,
      are relevant to the Irish agricultural industry. However, few data are available
      on the demographics of cows within a national population, either in Ireland or
      elsewhere, despite the recent development of comprehensive national cattle
      databases in many EU Member States. This study has sought: to determine the rate
      of cow culling from the national herd; to determine the rate of culling by type
      (dairy, beef), age, method of exit, date of exit and interval between last
      calving and exit; to calculate the national cow on-farm mortality rate; and to
      compare the Irish rates with published data from other countries. This work was
      conducted using data recorded in the national Cattle Movement Monitoring System
      (CMMS). Culling refers to the exit of cows from the national herd, as a result of
      death but regardless of reason, and cow-culling rate was calculated as the number
      of cow exits (as defined above) each year divided by the number of calf births in
      the same year. Culling rate was determined by type (dairy or beef), date of
      birth, method of exit (slaughter or on-farm death), month of exit and interval
      between last calving and exit. The average cow-culling rate during 2003 to 2006
      was 19.6% (21.3% for dairy, 18% for beef). While comparisons must be treated with
      caution, it concluded that the overall rates of culling in Ireland fell within
      published internationally accepted norms. The on-farm mortality rate of 3.2-4.1%
      was similar to that reported in comparable studies.

PMID- 21851718
TI  - Risk factors for the introduction and within-herd transmission of Mycobacterium
      avium subspecies paratuberculosis (MAP) infection on 59 Irish dairy herds.
AB  - Since 1994, Irish cattle have been exposed to greater risks of acquiring
      Mycobacterium avium subspecies paratuberculosis (MAP) infection as a consequence
      of the importation of over 70,000 animals from continental Europe. In recent
      years, there has been an increase in the number of reported clinical cases of
      paratuberculosis in Ireland. This study examines the prevalence of factors that
      promote the introduction and within-herd transmission of Mycobacterium avium
      subspecies paratuberculosis (MAP) on selected Irish dairy farms in the Cork
      region, and the association between these factors and the results of MAP
      screening tests on milk sock filter residue (MFR). A total of 59 dairy farms,
      selected using non-random methods but apparently free of endemic
      paratuberculosis, were enrolled into the study. A questionnaire was used to
      collect data about risk factors for MAP introduction and transmission. The MFR
      was assessed on six occasions over 24 months for the presence of MAP, using
      culture and immunomagnetic separation prior to polymerase chain reaction (IMS
      PCR). Furthermore, blood samples from all entire male and female animals over one
      year of age in 20 herds were tested by ELISA. Eighteen (31%) farms had operated
      as closed herds since 1994, 28 (47%) had purchased from multiple sources and 14
      (24%) had either direct or indirect (progeny) contact with imported animals. Milk
      and colostrum were mixed on 51% of farms, while 88% of farms fed pooled milk.
      Thirty (51%) herds tested negative to MFR culture and IMS-PCR, 12 (20%) were MFR
      culture positive, 26 (44%) were IMS-PCR positive and seven (12%) were both
      culture and IMS-PCR positive. The probability of a positive MFR culture was
      significantly associated with reduced attendance at calving, and with increased
      use of individual calf pens and increased (but not significantly) if mulitiple
      suckling was practised. There was poor agreement between MFR culture and MFR IMS
      PCR results, but moderate agreement between MFR culture and ELISA test results.
      This study highlights a lack of awareness among Irish dairy farmers about the
      effect of inadequate biosecurity on MAP introduction. Furthermore, within-herd
      transmission will be facilitated by traditional calf rearing and waste management
      practices. The findings of viable MAP in the presence of known transmission
      factors in non-clinically affected herds could be a prelude to long-term problems
      for the Irish cattle and agri-business generally.

PMID- 21851719
TI  - Tuberculosis in alpaca (Lama pacos) on a farm in Ireland. 1. A clinical report.
AB  - This case report describes tuberculosis (TB) due to infection with Mycobacterium
      bovis (M. bovis) in alpaca (Lama pacos) on a farm in Ireland. Two severely
      debilitated alpaca were presented to the University Veterinary Hospital,
      University College Dublin in November 2004. Bloods were taken, and haematology
      and biochemistry results were indicative of chronic infection. Radiological
      examination showed evidence of diffuse granulomatous pneumonia suggestive of
      tuberculosis. On necropsy there were granulomatous lesions present throughout
      many body organs including lung, liver, kidney, intestine as well on peritoneum
      and mesentery. Culture of acid-fast bacilli from lesions led to a diagnosis of
      tuberculosis due to M. bovis. The use of intradermal skin testing proved
      inefficient and unreliable for ante mortem diagnosis of tuberculosis in alpaca.
      Infection due to M. bovis should be considered among the differential diagnoses
      of debilitating diseases in alpaca, particularly those farmed in areas known to
      be traditional black spots for tuberculosis in cattle.

PMID- 21851720
TI  - Tuberculosis in alpaca (Lama pacos) on a farm in Ireland. 2. Results of an
      epidemiological investigation.
AB  - Tuberculosis (TB), due to infection with Mycobacterium bovis was diagnosed in a
      flock of alpaca in Ireland in 2004. An epidemiological investigation was
      conducted to identify the risk of TB for farmed alpaca where TB is endemic, the
      origin of the infection, the potential for alpaca-to-alpaca transmission and
      appropriate control measures. The investigation focused on the alpaca flock
      (including the farm, animal movements and breeding, feeding and flock health
      practice), the disease episode (including animal disease events and subsequent
      control measures) and TB infection risk in the locality. The TB risk to alpaca is
      high in areas where infection is endemic in cattle and badgers and where
      biosecurity is inadequate. It is most likely that the source of infection for the
      alpaca was a local strain of M. bovis, present in cattle in this area since at
      least 2001. Genotyping of isolates identified a single variable number tandem
      repeat (VNTR) profile in both cattle and alpaca in this region. Although a
      tuberculous badger was also removed from the vicinity, bacterial isolation was
      not attempted. On this farm, infection in alpaca was probably derived from a
      common source. Alpaca-to-alpaca transmission seems unlikely. Two broad control
      strategies were implemented, aimed at the rapid removal of infected (and
      potentially infectious) animals and the implementation of measures to limit
      transmission. Tests that proved useful in detecting potentially-infected animals
      included measurement of the albumin-to-globulin ratio and regular body condition
      scoring. Skin testing was time consuming and unproductive, and early detection of
      infected animals remains a challenge. The flock was managed as a series of
      separate groupings, based on perceived infection risk. No further TB cases have
      been detected.

PMID- 21851721
TI  - Acute haemoabdomen associated with Angiostrongylus vasorum infection in a dog: a
      case report.
AB  - A one-year-old intact female, Danish shorthaired pointer was referred to the
      emergency service with a history of acute collapse and pale mucous membranes
      after a month of reduced activity but with no other clinical signs. An ultrasound
      examination of the abdomen indicated the presence of a large amount of free fluid
      with no obvious cause such as neoplasia or splenic rupture. Fluid analysis had
      the macroscopic appearance of blood with no signs of infection or neoplasia.
      Multiple Angiostrongylus vasorum L1 larvae were revealed on a direct rectal
      faecal smear. The dog was treated with fenbendazole 25 mg/kg orally once daily
      for 20 days and given supportive treatment. The dog was stabilised on this
      treatment. Haemoabdomen is a clinical sign where surgical intervention is often
      considered an integral part of the diagnostic investigation (i.e., laparotomy) or
      treatment. Failing to make the diagnosis of canine angiostrongylosis before
      performing surgery may have a serious adverse affect on the outcome.
      Consequently, in areas where A. vasorum is enzootic, a Baermann test and a direct
      faecal smear should be included in the initial diagnostic investigation of all
      dogs presenting with bleeding disorders of unknown origin.

PMID- 21851722
TI  - Imbedding HACCP principles in dairy herd health and production management: case
      report on calf rearing.
AB  - Driven by consumer demands, European legislation has suggested the use of HACCP
      (Hazard Analysis Critical Control Point) as the quality risk management programme
      for the whole dairy chain. Until now, an exception has been made for primary
      producers, but as regulations evolve, on-farm HACCP-like programmes should be
      ready to assure food safety as well as animal health and animal welfare. In our
      field experiment, the HACCP-concept was used to combine both optimal farm
      management and formalisation of quality assurance in an on-farm situation in the
      Netherlands. The process of young stock rearing was chosen, since its importance
      for the future of the farm is often underestimated. Hazards and their associated
      risk factors can be controlled within the farm-specific standards and tolerances,
      as targets can be controlled by corrective measures and by implementation of farm
      specific worksheets. The veterinarian is pivotal for the facility-based HACCP
      team, since he/she has knowledge about on-farm risk assessment and relations
      between clinical pathology, feed and farm management. The HACCP concept in
      combination with veterinary herd health and production management programmes
      offers a promising approach to optimise on-farm production processes (i.e., young
      stock rearing) in addition to a structural approach for quality risk management
      on dairy farms.

PMID- 21851723
TI  - Farm management factors associated with bulk tank total bacterial count in Irish
      dairy herds during 2006/07.
AB  - Research has shown that total bacterial count (TBC), which is the bacterial
      growth per ml of milk over a fixed period of time, can be decreased by good
      hygiene and farm management practices. The objective of the current study was to
      quantify the associations between herd management factors and bulk tank TBC in
      Irish spring calving, grass-based dairy herds. The relationship between bulk tank
      TBC and farm management and infrastructure was examined using data from 400
      randomly selected Irish dairy farms where the basal diet was grazed grass. Herd
      management factors associated with bulk tank TBC were identified using linear
      models with herd annual total bacterial score (i.e., arithmetic mean of the
      natural logarithm of bulk tank TBC) included as the dependent variable. All herd
      management factors were individually analysed in a separate regression model,
      that included an adjustment for geographical location of the farm. A multiple
      stepwise regression model was subsequently developed. Median bulk tank TBC for
      the sample herds was 18,483 cells/ml ranging from 10,441 to 130,458 cells/ml.
      Results from the multivariate analysis indicated that the following management
      practices were associated with low TBC; use of heated water in the milking
      parlour; participation in a milk recording scheme; and tail clipping of cows at a
      frequency greater than once per year. Increased level of hygiene of the parlour
      and cubicles were also associated with lower TBC. Herd management factors
      associated with bulk tank TBC in Irish grazing herds were generally in agreement
      with most previous studies from confinement systems of milk production.

PMID- 21851724
TI  - Survival and dispersal of a defined cohort of Irish cattle.
AB  - An understanding of livestock movement is critical to effective disease
      prevention, control and prediction. However, livestock movement in Ireland has
      not yet been quantified. This study has sought to define the survival and
      dispersal of a defined cohort of cattle born in Co. Kerry during 2000. The cohort
      was observed for a maximum of four years, from January 1, 2000 to December 31,
      2004. Beef and dairy animals moved an average 1.31 and 0.83 times, respectively.
      At study end, 18.8% of the beef animals remained alive on Irish farms, including
      6.7% at the farm-of-birth, compared with 48.6% and 27.7% for dairy animals
      respectively. Beef animals werae dispersed to all Irish counties, but mainly to
      Cork, Limerick, Tipperary and Galway. Dairy animals mainly moved to Cork,
      Limerick, and Tipperary, with less animals going to Galway, Meath and Kilkenny.
      The four-year survival probability was 0.07 (male beef animals), 0.25 (male
      dairy), 0.38 (female beef), and 0.72 (female dairy). Although there was
      considerable dispersal, the number of moves per animal was less than expected.

PMID- 21851725
TI  - Omentalisation as adjunctive treatment of an infected femoral nonunion fracture:
      a case report.
AB  - A three-year-old male working border collie with an infected femoral nonunion
      fracture was managed in a two-stage procedure involving debridement and
      omentalisation, followed by stabilisation with a bone plate and an autogenous
      cancellous bone graft. Osseous union was documented radiographically 16 weeks
      after surgery. Telephone follow-up one year later revealed the dog had returned
      to full working function without evidence of lameness. To the authors' knowledge,
      this is the first clinical case described in the veterinary literature using
      omentalisation as an adjunct to the management of an infected, biologically
      inactive nonunion fracture.

PMID- 21851726
TI  - A non-invasive technique for standing surgical repair of urinary bladder rupture
      in a post-partum mare: a case report.
AB  - An 11-year-old mare presented 36 hours after foaling with a ruptured bladder.
      Uroperitoneum was diagnosed on ultrasound and from the creatinine concentration
      of the peritoneal fluid. Bladder endoscopy demonstrated tissue necrosis and a
      rent in the dorsocranial aspect of the bladder. Following stabilisation,
      including abdominal drainage and lavage, the mare was taken to standing surgery.
      Under continuous sedation and epidural anaesthesia, and after surgical
      preparation, a Balfour retractor was placed in the vagina. Using sterile
      lubricant and moderate force, it was possible to insert a hand into the bladder.
      The tear was easily palpable on the dorsal portion of the bladder. Two fingers
      were inserted through the tear and used to provide traction to evert the bladder
      completely into the vagina where it could grasped with the surgeons other hand to
      prevent further trauma. A second surgeon could then visualise the entire tear and
      repaired this using a single layer of size zero PDS suture in a single continuous
      pattern. As soon as the bladder was repaired, it was replaced via the urethra.
      The mare did well after surgery and was discharged after 48 hours, apparently
      normal.This report is the first describing repair of the bladder without an
      abdominal incision or incision into the urethral sphincter. This greatly reduces
      the chance of possible complications such as urine pooling after surgery with the
      previously described standing technique or bladder trauma due to traction with
      abdominal surgery.

PMID- 21851727
TI  - A review of Ireland's waterbirds, with emphasis on wintering migrants and
      reference to H5N1 avian influenza.
AB  - Ireland is characterised by its diversity and large abundance of wetlands, making
      it attractive to a wide variety of waterbirds throughout the year. This paper
      presents an overview of Ireland's waterbirds, including ecological factors
      relevant to the potential introduction, maintenance, transmission and spread of
      infectious agents, including the H5N1 avian influenza virus, in Ireland.
      Particular emphasis is placed on five groups of wintering migrants (dabbling and
      sieving wildfowl, grazing wildfowl, diving wildfowl, waders and gulls), noting
      that the H5N1 avian influenza virus has mainly been isolated from this subset of
      waterbirds. Ireland's wetlands are visited during the spring and summer months by
      hundreds of thousands of waterbirds which come to breed, predominantly from
      southern latitudes, and during the autumn and winter by waterbirds which come
      from a variety of origins (predominantly northern latitudes), and which are
      widely distributed and often congregate in mixed-species flocks. The
      distribution, feeding habits and social interactions of the five groups of
      wintering migrants are considered in detail. Throughout Ireland, there is
      interaction between different waterbird populations (breeding migrants, the
      wintering migrants and resident waterbird populations). There is also a regular
      and complex pattern of movement between feeding and roosting areas, and between
      wetlands and farmland. These interactions are likely to facilitate the rapid
      transmission and spread of the H5N1 avian influenza virus, if it were present in
      Ireland.

PMID- 21851729
TI  - Nutritional muscular dystrophy in a four-day-old Connemara foal.
AB  - This report describes a four-day-old, full-term Connemara colt, presented for the
      evaluation of a progressive inability to rise unassisted. A diagnosis of
      nutritional muscular dystrophy was made based on muscular weakness, elevated
      muscle enzymes and low vitamin E, selenium and glutathione peroxidase activity.
      The foal was treated with intramuscular vitamin E-selenium and made a full
      recovery.

PMID- 21851728
TI  - Analgesic management of an eight-year-old Springer Spaniel after amputation of a
      thoracic limb.
AB  - Analgesic agents were administered perioperatively to an eight-year-old Springer
      Spaniel undergoing amputation of its right thoracic limb. The amputation was
      carried out due to a painful, infiltrative and poorly differentiated sarcoma
      involving the nerves of the brachial plexus. A combination of pre-emptive and
      multimodal perioperative analgesic strategies was used; including intravenous
      (IV) infusions of fentanyl, morphine, lidocaine and ketamine.

PMID- 21851730
TI  - An evaluation of Irish cattle herds with inconclusive serological evidence of
      bovine brucellosis.
AB  - Since 1998, there has been a steady decline in herd restrictions and de
      populations in Ireland due to bovine brucellosis. There is concern that the
      interpretation of laboratory results may become increasingly problematic, as
      brucellosis prevalence falls in Ireland. Therefore, the purpose of the current
      study was to evaluate the infection status of Irish herds and animals with
      inconclusive serological evidence of bovine brucellosis. During 12 months from
      September 1, 2004, laboratory and observational epidemiological data were
      collected from all Irish herds where animal testing identified at least one
      animal with a complement fixation test (CFT) reading greater than zero and/or a
      positive result to the indirect enzyme-linked immunosorbent assay (iELISA). Due
      to the observational nature of the study, we have robust estimates of the
      relative, but not the absolute, performance of the CFT, iELISA and brucellin skin
      test (BST). Herds were divided into three categories (Group A, B or C) on the
      basis of test results at initial assessment. A total of 639 herds were enrolled
      into the study, and observed for at least two years following enrolment. A rising
      CFT titre, with a CFT reading of 111 International CFT Units (IU) or greater at
      the subsequent blood test, was generally associated with herds where other
      evidence of infection was also available. Knowledge of the CFT reading at the
      initial and a subsequent blood test proved useful in distinguishing false
      positive and true-positive brucellosis results. There was poor correlation
      between the CFT and iELISA results, and between the CFT and BST results. As a
      result of this study, national policy has been modified to include re-sampling of
      all animals with CFT readings of 20 IU or greater. This project has also led to a
      reduction in the number of herds restricted, as well as restriction duration. It
      has also contributed to a reduction in the number of herds listed for contiguous
      tests, and therefore the potential for contiguity testing of false positive
      results.

PMID- 21851731
TI  - An all-island approach to mapping bovine tuberculosis in Ireland.
AB  - This study used techniques in Geographical Information Systems (GIS) to explore
      the spatial patterns of bovine tuberculosis (TB) in the whole island of Ireland
      over an 11-year period. This is the first time that data pertaining to TB from
      the Republic of Ireland and Northern Ireland have been collated and examined in
      an all-Ireland context. The analyses were based on 198, 156 point locations
      representing active farms with cattle in Northern Ireland and the Republic of
      Ireland between the years 1996 and 2006. The results consist of a series of maps
      giving a visual representation of cattle populations and associated detected bTB
      levels on the island of Ireland over this time interval.

PMID- 21851732
TI  - Focus on bovine mastitis: knowledge into practice.

PMID- 21851733
TI  - Paratuberculosis sero-status and milk production, SCC and calving interval in
      Irish dairy herds.
AB  - The objective of this study was to investigate the impact of paratuberculosis
      sero-status on milk yield, fat, protein, somatic cell count and calving interval
      in Irish dairy herds. Serum from all animals over 12 months of age (n = 2,602) in
      34 dairy herds was tested for antibodies to Mycobacterium avium subsp.
      paratuberculosis using an ELISA. Herds were categorised by sero-status into
      positive, non-negative and negative, where a positive herd contained two or more
      positive cows, a non-negative herd contained only one positive cow and a negative
      herd contained no positive cows. Data at animal, parity and herd-level were
      analysed by multiple regression using general linear models. Positive herds (mean
      herd size = 129 cows) and non-negative herds (81 cows) were larger than negative
      herds (72 cows) (P < 0.01). Negative herds had the highest economic breeding
      index (EBI), while positive herds had the highest estimated breeding value (EBV)
      for milk yield. There was no significant effect of paratuberculosis sero-status
      at animal, parity or herd-level on milk yield, milk fat or protein production,
      somatic cell count score (SCCS) or calving interval. Negative herds tended to
      have a lower SCCS than positive and nonnegative herds (P = 0.087). This study
      only examined the effects of paratuberculosis sero-status but did not examine the
      clinical effects of Johne's disease at the farm or dairy industry levels.

PMID- 21851734
TI  - Correlation of the Havemeyer endoscopic laryngeal grading system with
      histopathological changes in equine Cricoarytenoideus dorsalis muscles.
AB  - The establishment of a single validated endoscopic laryngeal grading system for
      assessing recurrent laryngeal neuropathy (RLN) is desirable to facilitate direct
      comparisons between the findings of different clinical and research groups
      worldwide. The objective of this study was to assess the relationship between the
      Havemeyer endoscopic laryngeal grading system and histopathological changes
      consistent with RLN in the left cricoarytenoideus dorsalis (CAD) muscle of horses
      of different breeds with a full range of clinical severities of RLN, i.e., from
      normal endoscopic laryngeal function to complete laryngeal hemiplegia. Endoscopic
      grading of laryngeal function of 22 horses was performed using the Havemeyer
      endoscopic laryngeal grading system. A biopsy sample of the left CAD muscle was
      obtained from each horse, either at post mortem examination (n = 16), or during
      routine laryngoplasty surgery (n = 6). A semi-quantitative histopathological
      scoring system was used to grade the severity of histopathological lesions
      consistent with RLN in the left CAD muscle of each horse. A significant positive
      correlation (rs = 0.705, p < 0.001) was found between the Havemeyer grades and
      sub-grades of laryngeal function and the semi-quantitative assessment of
      histopathological lesions consistent with RLN in the left CAD muscle. However, a
      wide spread of muscle histopathological scores was obtained, particularly from
      horses with Havemeyer sub-grades II.1, III.1 and III.2. In conclusion, the
      Havemeyer endoscopic laryngeal grading system was found to broadly correlate with
      histopathological changes consistent with RLN in equine cricoarytenoideus
      dorsalis muscle.

PMID- 21851735
TI  - An outbreak of tuberculosis affecting cattle and people on an Irish dairy farm,
      following the consumption of raw milk.
AB  - Bovine tuberculosis is an ongoing problem in Ireland, and herd incidence has
      remained at approximately 5% for some years. Spillover of infection from cattle
      to people remains an ever-present possibility, given the ongoing pool of
      infection in the Irish cattle population. This paper describes an outbreak of
      tuberculosis affecting cattle and people on a dairy farm in southeastern Ireland
      following the consumption of milk from a seven-year-old cow with tuberculous
      mastitis. Twenty-five of 28 calves born during autumn 2004 and spring 2005 were
      subsequently identified as TB reactors, and five of six family members were
      positive on the Mantoux test. During 2005, milk from this cow had mainly been
      used to feed calves, and was added only occasionally to the bulk tank. Therefore,
      the calves each received infected milk on an almost continuous basis between
      birth and weaning. The family collected milk from the bulk milk tank, and
      consumed it without pasteurisation. This case highlights the risks associated
      with the consumption of raw milk. In this family, TB has had a very significant
      impact on the health of two young children. These risks are well recognised, and
      relevant information for farmers is available. It is of concern, therefore, that
      raw milk consumption remains prevalent on Irish farms. New strategies are needed,
      in partnership with industry, to address this important issue. KEYWORDS: bovine
      tuberculosis, Ireland, mastitis, milk, Mycobacterium bovis, pasteurisation, TB,
      zoonosis.

PMID- 21851736
TI  - Demographics of cattle positive for Mycobacterium avium subspecies
      paratuberculosis by faecal culture, from submissions to the Cork Regional
      Veterinary Laboratory.
AB  - The demography of bovine infections caused by Mycobacterium avium subspecies
      paratuberculosis (MAP) in Ireland is poorly defined. The objective of this study
      was to describe the demographics of cattle positive to MAP on faecal culture,
      based on submissions to the Cork Regional Veterinary Laboratory (Cork RVL) from
      1994 to 2006. The study focused on all available faecal samples from adult cattle
      with non-responsive chronic diarrhoea that were submitted by private veterinary
      practitioners to Cork RVL for MAP culture. For each MAP-positive by faecal
      culture animal, data were collated from Cork RVL and Cattle Movement Monitoring
      Scheme (CMMS) records. Johne's disease (JD) was confirmed in 110 animals from 86
      herds by the Cork RVL between 1994 and 2006, with a rate of positive cases
      between 15% and 18% over last four years of the study. Two breeds
      (Holstein/Friesian or Limousin) made up 78% of submissions. Movements were
      assessed for the 57 study animals with available movement information, 90% died
      within one year of the test and 26% tested positive in the herd they were born
      into. The study provides preliminary information about movement trends and
      demographics of animals with MAP positive submissions. Although the study area is
      restricted, it includes the most intensive (and economically-important) dairy
      region in Ireland. The demographics of JD infection from the study area are in
      agreement with international reports. Further work is required to determine
      demographic trends, incidence and prevalence of JD throughout Ireland. It is
      hoped this work may contribute to the development of a surveillance strategy for
      MAP by regional veterinary laboratories.

PMID- 21851737
TI  - Molecular epidemiology of clinical isolates of Pseudomonas aeruginosa isolated
      from horses in Ireland.
AB  - Clinical isolates (n = 63) of Pseudomonas aeruginosa obtained from various sites
      in 63 horses were compared using ERIC2 RAPD PCR to determine their genetic
      relatedness. Resulting banding patterns (n = 24 genotypes) showed a high degree
      of genetic heterogeneity amongst all isolates examined, indicating a relative non
      clonal relationship between isolates from these patients, employing this
      genotyping technique. This study characterised 63 clinical isolates into 24
      distinct genotypes, with the largest cluster (genotype E) accounting for 10/63
      (15.9%) of the isolates. ERIC2 RAPD PCR proved to be a highly discriminatory
      molecular typing tool of P. aeruginosa in isolates recovered from horses. With
      the adoption of several controls to aid reproducibility, this technique may be
      useful as an alternative to PFGE, particularly in epidemiological investigations
      of outbreaks where speed may be a significant parameter. This is the first report
      of clonal heterogeneity amongst P. aeruginosa from horses and demonstrated that
      ERIC RAPD PCR is a rapid method for the examination of this species in horses,
      which may be useful in outbreak analysis.

PMID- 21851738
TI  - Effect of pre-milking teat preparation procedures on the microbial count on teats
      prior to cluster application.
AB  - A study was carried out to investigate the effect of six pre-milking teat
      preparation procedures on lowering the staphylococal, streptococcal and coliform
      microbial count on teat skin prior to cluster application. The teat preparations
      included 'Iodine', 'Chlorhexidine' teat foam, 'Washing and drying' with paper,
      'No preparation', 'Chlorine' teat foam, and disinfectant 'Wipes'. Teat
      preparations were applied for five days to 10 cows for each treatment during two
      herd management periods (indoors and outdoors). Teats were swabbed on day four
      and five before teat preparation and repeated after teat preparation. The swabs
      were plated on three selective agars: Baird Parker (Staphylococcus spp.), Edwards
      (Streptococcus spp.), and MacConkey (coliform). Following incubation, microbial
      counts for each pathogen type were manually counted and assigned to one of six
      categories depending on the microbial counts measured. The results were analysed
      by logistic regression using SAS 28. The main analysis was conducted on binary
      improvement scores for the swabbing outcomes. There were no differences for
      staphylococcal, streptococcal and coliform bacterial counts between treatments,
      measured 'before' teat preparation. Treatments containing 'Chlorhexidine' teat
      foam (OR = 4.46) and 'Wipes' (OR = 4.46) resulted in a significant reduction (P <
      0.01) in the staphylococcal count on teats compared to 'Washing and drying' or
      'No preparation'. 'Chlorine' teat foam (OR = 3.45) and 'Wipes' (3.45) had the
      highest probability (P < 0.01) of reducing streptococcal counts compared to
      'Washing and drying' or 'No preparation'. There was no statistical difference
      between any of the disinfectant treatments applied in reducing coliforms. Thus,
      the use of some disinfectant products for pre-milking teat preparation can have
      beneficial effects on reducing the levels of staphylococcal and streptococcal
      pathogens on teat skin.

PMID- 21851739
TI  - Direct and indirect effects of Johne's disease on farm and animal productivity in
      an Irish dairy herd.
AB  - Johne's disease (JD) is caused by infection with the organism Mycobacterium avium
      spp. paratuberculosis, leading to chronic diarrhoea and ill thrift in adult
      cattle. JD is considered to adversely affect farm performance and profitability.
      This retrospective case study was undertaken on a single commercial dairy herd in
      the south west of Ireland. Animal production records were interrogated to assess
      the effect of JD on milk yield (total kg per lactation), somatic cell count (the
      geometric mean over the lactation), reasons for culling, cull price and changes
      in herd parity structure over time. JD groups were defined using clinical signs
      and test results. One control animal was matched to each case animal on parity
      number and year. Specific lactations (clinical, pre-clinical and test-positive
      only) from 1994 to 2004 were compared between JD case and control cows. A
      significantly lower milk yield (1259.3 kg/lactation) was noted from cows with
      clinical JD in comparison to their matched control group. Clinical animals had an
      average cull price of ?516 less than animals culled without signs of clinical
      disease. In contrast, little effect was noted for sub-clinical infections. These
      direct effects of JD infections, in combination with increased culling for
      infertility and increasing replacement rates, had a negative impact on farm
      production. Results from this study provide preliminary information regarding the
      effects of JD status on both herd and animal-level performance in Ireland.

PMID- 21851740
TI  - Prevalence and distribution of paratuberculosis (Johne's disease) in cattle herds
      in Ireland.
AB  - A simple random survey was conducted in Ireland during 2005 to estimate the ELISA
      prevalence of paratuberculosis, commonly called Johne's disease (JD), in the
      cattle population. Serum samples were collected from all 20,322 females/breeding
      bulls over 12 months-of-age in 639 herds. All samples were tested using a
      commercially available absorbed ELISA. The overall prevalence of infected herds,
      based on the presence of at least one ELISA-positive animal, was 21.4% (95% CI
      18.4%-24.9%). Herd prevalence levels amongst dairy herds (mean 31.5%; 95% CI:
      24.6%, 39.3%) was higher than among beef herds (mean 17.9%; 95% CI: 14.6%-21.8%).
      However, the animal level prevalence was similar. The true prevalence among all
      animals tested, was calculated to be 2.86% (95%CI: 2.76, 2.97) and for animals >=
      2 yrs, it was 3.30% (95%CI: 3.17, 3.43). For animals in beef herds, true
      prevalence was 3.09% (95%CI: 2.93, 3.24), and for those in dairy herds, 2.74%
      (95%CI: 2.59, 2.90). The majority of herds had only one ELISA-positive infected
      animal. Only 6.4% (95% CI 4.7%-8.7%) of all herds had more than one ELISA
      positive infected animal; 13.3% (CI 8.7%-19.7%) of dairy herds ranging from two
      to eight ELISA-positive infected animals; and, 3.9% beef herds (CI 2.4%-6.2%)
      ranging from two to five ELISA-positive infected animals. The true prevalence of
      herds infected and shedding Mycobacterium avium subspecies paratuberculosis is
      estimated to be 9.5% for all herd types; 20.6% for dairy herds; and 7.6% for beef
      herds. If ELISA positive animals <2-years-of-age are excluded, the true herd
      prevalene reduces to: 9.3% for all herd types; 19.6% for dairy herds; and 6.3%
      for beef herds based on a test specificity (Sp) of 99.8% and test sensitivity
      (Se) (i.e., ability to detect culture-positive, infected animals shedding at any
      level) of 27.8-28.9%.

PMID- 21851741
TI  - Causes of disease and death from birth to 12 months of age in the Thoroughbred
      horse in Ireland.
AB  - A retrospective study was carried out to investigate the causes of disease and
      death in a population of foals in Ireland during their first 12 months post
      partum. Foaling and veterinary records from 343 foals on four farms born between
      January 1, 2004 and May 30, 2008 were reviewed. Among 343 foals, 22 did not
      survive to 12 months of age. Over the five-year period, the incidence of
      stillbirth was 1.5% (5/343), mortality 5% (17/338) and overall morbidity was
      88.5% (299/338). Morbidity was calculated to include all new conditions brought
      to the attention of the attending veterinary surgeon, no matter how minor. Of
      foals born alive: congenital abnormalities were the most common cause of death
      (35.3% 6/17 foals) followed by musculoskeletal trauma (5/17, 29.4%). Of 711
      separate incidents of disease, 46.5% (331/711) were due to an infectious process,
      25% (178/711) due to non-infectious musculoskeletal issues; and 14.9% (106/711)
      related to non-infectious gastrointestinal problems. Respiratory infection was
      the single most common disease accounting for 27.8% (178/711) of all disease
      incidents in this population. Findings from this study provide information
      regarding the causes and incidence of death and disease in the young Irish
      Thoroughbred population.

PMID- 21851742
TI  - An investigation into reduced milk production following dietary alteration on an
      Irish dairy farm.
AB  - A nutritional evaluation of an Irish dairy herd indicated gross overfeeding of
      late lactation cows, over-conditioning of cows at parturition and a high rate of
      body condition loss in early lactation. Metabolisable-energy based nutritional
      modelling software was used to guide recommended dietary changes to prevent
      excessive condition gain in late lactation. Immediately following the
      implementation of the changes there was an unexpected reduction in performance
      affecting both milk yield and protein concentration. An investigation into the
      poor performance revealed underestimation of peak milk yield; over-estimation of
      maize silage quality; a large difference in the concentrate being fed compared to
      the concentrate recommended, and failure of the blend of concentrate ingredients
      to maintain the intended proportions in the in-parlour feeding system. The
      estimated maximum cumulative effect of these errors was to cause undersupply of
      energy and protein in the recommended diet of 16% and 3% respectively to cows in
      early lactation. Use of a net-energy nutritional model would have indicated a
      requirement for a higher energy supply in this case. This report highlights the
      challenges in obtaining accurate on-farm data for use in dairy cow nutritional
      models.

PMID- 21851743
TI  - A survey of bone integrity from cull sows in Ireland.
AB  - The objective of this study was to examine the differences in sow metacarpal
      properties through various parities and to compare the incidence of locomotory
      problems between stalled and loose-housed sows. Metacarpals (n = 110) of sows
      from six farms were collected at slaughter and stored at -20 degrees C. Bones
      from one forelimb of sows in stalls (n = 36) and loose-housed (n = 20) were
      collected and their articular surfaces examined for Osteochondrosis Dissecans
      (OCD), these sows were also scored for lameness pre-slaughter. Metacarpals were
      CT scanned for cross sectional area and moment of inertia. Cylindrical sections
      from the diaphysis were used for mechanical testing and calculating bone strength
      indices. The results show there was little change in bone mineral status
      throughout the range of parities examined and overall metacarpal integrity was
      not compromised by multiple production cycles. There were no differences detected
      in the incidence of lameness or joint pathology between housing systems.

PMID- 21851744
TI  - Oesophageal foreign bodies in dogs: factors affecting success of endoscopic
      retrieval.
AB  - Oesophageal foreign bodies are common in dogs. Endoscopic removal is a viable
      treatment option but few studies have assessed the clinical and radiographic
      features that would be useful in decision-making and prognosis.Dogs (n = 44) with
      oesophageal foreign bodies presented to the University Veterinary Hospital were
      assessed. Terriers and West Highland White Terriers were significantly
      overrepresented (p < 0.0001) and in those breeds the foreign body was
      significantly (p < 0.0001) more likely to be located caudal to the heart base.
      The majority (88.6%) of foreign bodies were bones or bone fragments.Group 1 (n =
      30) included animals where endoscopic removal was successful and Group 2 (n = 14)
      animals where it was unsuccessful or not attempted because of evidence of
      oesophageal rupture. There was no statistically significant difference in age,
      sex, body weight, type, location and size of foreign body, recovery rate, short
      term complications and long-term outcome between the two groups. Duration of
      signs prior to presentation and time to spontaneous oral feeding were
      significantly longer (p < 0.01 in each case) in Group 2 (five days and 120 hours,
      respectively) compared to Group 1 (2 days and 24 hours, respectively). Mortality
      was 11.1%. Long-term follow-up of 29 dogs suggested oesophageal stricture
      formation manageable by feeding alone in seven (24.1%) cases.Terriers appear
      predisposed to oesophageal foreign bodies. Success of endoscopic removal is
      adversely affected by duration of signs prior to presentation. Surgical removal
      negatively influences time to recovery. Stricture formation appears to be a
      relatively common complication and alternate measures for its prevention should
      be sought.

PMID- 21851745
TI  - Veterinary dairy herd fertility service provision in seasonal and non-seasonal
      dairy industries - a comparison.
AB  - The decline in dairy herd fertility internationally has highlighted the limited
      impact of traditional veterinary approaches to bovine fertility management. Three
      questionnaire surveys were conducted at buiatrics conferences attended by
      veterinary practitioners on veterinary dairy herd fertility services (HFS) in
      countries with a seasonal (Ireland, 47 respondents) and non-seasonal breeding
      model (The Netherlands, 44 respondents and Portugal, 31 respondents). Of the 122
      respondents, 73 (60%) provided a HFS and 49 (40%) did not. The majority (76%) of
      all practitioners who responded stated that bovine fertility had declined in
      their practice clients' herds with inadequate cow management, inadequate
      nutrition and increased milk yield as the most important putative causes. The
      type of clients who adopted a herd fertility service were deemed more educated
      than average (70% of respondents), and/or had fertility problems (58%) and/or
      large herds (53%). The main components of this service were routine postpartum
      examinations (95% of respondents), fertility records analysis (75%) and
      ultrasound pregnancy examinations (69%). The number of planned visits per annum
      varied between an average of four in Ireland, where breeding is seasonal, and 23
      in Portugal, where breeding is year-round. The benefits to both the practitioner
      and their clients from running a HFS were cited as better fertility, financial
      rewards and job satisfaction. For practitioners who did not run a HFS the main
      reasons given were no client demand (55%) and lack of fertility records (33%).
      Better economic evidence to convince clients of the cost-benefit of such a
      service was seen as a major constraint to adoption of this service by 67% of
      practitioners.

PMID- 21851746
TI  - latrogenic lipoid pneumonia in an adult horse.
AB  - A 20-year-old gelding presented with a history of acute respiratory distress
      which began immediately after administration of a mineral oil and water mix, via
      nasogastric intubation, for treatment of suspected gastrointestinal dysfunction.
      An initial presumptive diagnosis of acute lipoid pneumonia was made; this was
      further supported by evidence of arterial hypoxaemia and oxygen desaturation on
      arterial blood gas analysis, ultrasonographic signs of bilateral ventral lung
      consolidation and a mixed bronchoalveolar-interstitial lung pattern seen on
      thoracic radiographs. Despite intensive supportive therapy the horse's condition
      continued to deteriorate and the decision was made for humane euthanasia. Gross
      necropsy findings supported the clinical diagnosis of lipoid pneumonia.

PMID- 21851747
TI  - Antimicrobial resistance in commensal faecal Escherichia coli of hospitalised
      horses.
AB  - The objective of this study was to examine the impact of hospitalisation and
      antimicrobial drug administration on the prevalence of resistance in commensal
      faecal E. coli of horses. Faecal samples were collected from ten hospitalised
      horses treated with antimicrobials, ten hospitalised horses not treated with
      antimicrobials and nine non-hospitalised horses over a consecutive five day
      period and susceptibility testing was performed on isolated E. coli. Results
      revealed that hospitalisation alone was associated with increased prevalence of
      antimicrobial resistance and multidrug resistance in commensal E. coli of horses.
      Due to the risk of transfer of resistance between commensal and pathogenic
      bacteria, veterinarians need to be aware of possible resistance in commensal
      bacteria when treating hospitalised horses.

PMID- 21851748
TI  - Immune-mediated thrombocytopenia associated with angiostrongylus vasorum
      infection in a Jack Russell terrier.
AB  - A twenty-month-old Jack Russell terrier was presented with a four-day history of
      thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise
      tolerance. Clinical examination revealed several petechial haemorrhages on the
      gingivae and small echymotic haemorrhages in the inguinal region, along with mild
      bilateral epistaxis. Haematology confirmed a platelet count of 1.0 * 10/L.
      Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung
      pattern, apparent throughout the entire lungfield, but particularly marked within
      the left lung lobes. A presumptive diagnosis of immune-mediated thrombocytopenia
      was made and the dog was treated with vincristine and immunosuppressive doses of
      prednisolone. Initially anaemia developed following gastrointestinal haemorrhage;
      however, after symptomatic treatment the dog showed a marked clinical
      improvement. Evaluation for an underlying cause of the disease revealed
      Angiostrongylus vasorum L1 larvae on faecal analysis and treatment with
      fenbendazole was commenced. The dog made a full clinical recovery with all
      treatment was withdrawn within five weeks of diagnosis. This is the second report
      of immune-mediated thrombocytopenia associated with Angiostrongylus vasorum
      infection and it is the first to be successfully managed. The report highlights
      that Angiostrongylus vasorum should be considered in young dogs presented with
      thrombocytopenia.

PMID- 21851749
TI  - A review of bovine cases consigned under veterinary certification to emergency
      and casualty slaughter in Ireland during 2006 to 2008.

PMID- 21851750
TI  - Diagnosis of vaginal discharge by wet mount microscopy: a simple and underrated
      method.
AB  - Vaginal discharge is highly variable in quality and quantity among different
      individuals, and even in the same individual during different periods of life.
      Vaginal discharge is most commonly caused by infection with sexually transmitted
      organisms or increased colonization by different facultative pathogenic
      microorganisms (i.e., Gardnerella vaginalis). Noninfectious causes of vaginal
      discharge are quite rare (10% noninfectious as compared to 90% infectious
      causes). Most common in women with a vaginal infection is bacterial vaginosis
      (40%-50% of cases), followed by vulvovaginal candidosis (20%-25%), and then
      trichomoniasis (15%-20%). If infection is suspected as the primary cause, a
      sample of the vaginal discharge should be taken and examined microscopically.
      When evaluating vaginal secretions by phase-contrast wet mount microscopy,
      knowledge of what is normal versus abnormal is very important. Knowledge of the
      sensitivity and specificity of wet mount microscopy in different clinical
      settings is also important. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians LEARNING OBJECTIVES: After completing this CME activity,
      physicians should be better able to evaluate lifetime changes in vaginal
      secretions, characterize the physiological and pathological appearance of vaginal
      discharge, assess the clinical practicality and usefulness of wet mount
      microscopy and use wet mount microscopy to diagnose bacterial vaginosis and other
      common vaginal infections.

PMID- 21851751
TI  - Arthrogryposis: a review and approach to prenatal diagnosis.
AB  - Congenital contractures are a common ultrasound finding. Arthrogryposis, defined
      as multiple contractures involving more than one area of the body, is not a
      specific diagnosis but rather a description of clinical findings. It is
      associated with more than 300 different disorders, many of which have other
      associated malformations and/or neurocognitive delay. Lack of fetal movement or
      akinesia commonly accompanies the contractures. The underlying diagnosis may be
      the result of a neurogenic or myopathic process, a connective tissue disorder,
      intrauterine compression, a teratogenic exposure or vascular insult. When a
      patient presents with arthrogryposis, the challenge for obstetricians is to
      assess the fetal condition, associated abnormalities and family history to offer
      the most accurate counseling and diagnosis. A multidisciplinary approach
      incorporating obstetrics, genetics, pediatric neurology, and fetopathology is
      warranted. Prenatal diagnostic testing options are available. Postnatal
      evaluation by pediatric specialists is important and offers enhanced diagnostic
      capabilities and recurrence risk counseling. We present an organized approach to
      the prenatal assessment of arthrogryposis as well as recommendations for
      intrapartum and postpartum care. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians LEARNING OBJECTIVES: After completing this CME activity,
      physicians should be better able to define arthrogryposis and identify a
      classification framework to approach prenatal diagnosis, develop a differential
      diagnosis for a fetus who demonstrates arthrogryposis, formulate an action plan
      for prenatal diagnosis and assess the importance of a multidisciplinary approach
      to counseling and care when a fetus is identified to have arthrogryposis.

PMID- 21851752
TI  - Therapy of hyperthyroidism in pregnancy and breastfeeding.
AB  - Uncontrolled hyperthyroidism in pregnancy is associated with an increased risk of
      perinatal complications. The state of the art discussed here has been derived
      through a wide MEDLINE search throughout English-language literature by using a
      combination of words such as hyperthyroidism, propylthiouracil (PTU),
      methimazole, rituximab, and pregnancy to identify original related works and
      review articles. Thioamides are the main first-line therapeutic options, whereas
      beta-blockers and iodine are second-choice drugs; surgery is resorted to only in
      exceptional cases. Methimazole and PTU reduce the production of thyroid hormones
      by selectively inhibiting thyroid peroxidase. PTU was once considered to be the
      first-choice drug in the treatment of gestational hyperthyroidism; however, the
      United States Food and Drug Administration now recommends it as a second-line
      thioamide, which should be used solely by women in their first trimester of
      pregnancy. Thyroidectomy is to be carried out only in pregnant women affected by
      life-threatening, uncontrollable hyperthyroidism, or in cases with thioamide
      intolerance. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians
      LEARNING OBJECTIVES: After completion of this article, the physician should be
      better able to choose appropriate therapies for hyperthyroidism in pregnant
      women, assess the risk of possible complications due to maternal hyperthyroidism,
      and evaluate strategies for patient follow-up.

PMID- 21851753
TI  - Beyond the 'iron lungs of gerontology': using evidence to shape the future of
      nursing homes in Canada.
AB  - Institutionalization of the Elderly in Canada suggested that efforts to address
      the underlying causes of age-related declines in health might negate the need for
      nursing homes. However, the prevalence of chronic disease has increased, and
      conditions like dementia mean that nursing homes are likely to remain important
      features of the Canadian health care system. A fundamental problem limiting the
      ability to understand how nursing homes may change to better meet the needs of an
      aging population was the lack of person-level clinical information. The
      introduction of interRAI assessment instruments to most Canadian
      provinces/territories and the establishment of the national Continuing Care
      Reporting System represent important steps in our capacity to understand nursing
      home care in Canada. Evidence from eight provinces and territories shows that the
      needs of persons in long-term care are highly complex, resource allocations do
      not always correspond to needs, and quality varies substantially between and
      within provinces.

PMID- 21851754
TI  - Individual therapy attrition rates in a low-intensity service: a comparison of
      cognitive behavioural and person-centred therapies and the impact of deprivation.
AB  - BACKGROUND: This paper looks at attrition in relation to deprivation and type of
      therapy - CBT or person-centred counselling. METHOD: Case notes of all those
      referred in a 4-month period (n = 497) were assessed for those who failed to opt
      in; those who opted-in but failed to attend first appointment and those who
      attended first appointment but subsequently dropped-out. RESULTS: Significant
      numbers failed to opt-in, attend first appointment or dropped out during therapy.
      There were no differences between CBT and PCT. Those from the most deprived areas
      were less likely to opt-in. CONCLUSIONS: We need to develop better approaches to
      attracting and maintaining contact with individuals complaining of common mental
      health problems.

PMID- 21851755
TI  - Epigallocatechin gallate changes mRNA expression level of genes involved in
      cholesterol metabolism in hepatocytes.
AB  - Catechins, compounds derived from green tea, have been shown to improve
      cholesterol metabolism in animal studies, but the molecular mechanisms underlying
      this function have not been fully understood. We performed DNA microarray
      analysis in order to clarify the effects of epigallocatechin gallate (EGCG), the
      dominant catechin in green tea, on cholesterol metabolism in HepG2 hepatocytes.
      This revealed that the expression levels of several genes related to cholesterol
      metabolism, including the LDL receptor, were changed by EGCG treatment. Using a
      real-time PCR technique, we confirmed that EGCG treatment up-regulated mRNA
      expression level of the LDL receptor. Moreover, EGCG decreased extracellular apoB
      levels. These findings indicated that EGCG improves cholesterol metabolism
      through the up-regulation of LDL receptor and also reduces extracellular apoB
      levels.

PMID- 21851756
TI  - The protective effect of supplemental calcium on colonic permeability depends on
      a calcium phosphate-induced increase in luminal buffering capacity.
AB  - An increased intestinal permeability is associated with several diseases.
      Previously, we have shown that dietary Ca decreases colonic permeability in rats.
      This might be explained by a calcium-phosphate-induced increase in luminal
      buffering capacity, which protects against an acidic pH due to microbial
      fermentation. Therefore, we investigated whether dietary phosphate is a co-player
      in the effect of Ca on permeability. Rats were fed a humanised low-Ca diet, or a
      similar diet supplemented with Ca and containing either high, medium or low
      phosphate concentrations. Chromium-EDTA was added as an inert dietary intestinal
      permeability marker. After dietary adaptation, short-chain fructo
      oligosaccharides (scFOS) were added to all diets to stimulate fermentation,
      acidify the colonic contents and induce an increase in permeability. Dietary Ca
      prevented the scFOS-induced increase in intestinal permeability in rats fed
      medium- and high-phosphate diets but not in those fed the low-phosphate diet.
      This was associated with higher faecal water cytotoxicity and higher caecal
      lactate levels in the latter group. Moreover, food intake and body weight during
      scFOS supplementation were adversely affected by the low-phosphate diet.
      Importantly, luminal buffering capacity was higher in rats fed the medium- and
      high-phosphate diets compared with those fed the low-phosphate diet. The
      protective effect of dietary Ca on intestinal permeability is impaired if dietary
      phosphate is low. This is associated with a calcium phosphate-induced increase in
      luminal buffering capacity. Dragging phosphate into the colon and thereby
      increasing the colonic phosphate concentration is at least part of the mechanism
      behind the protective effect of Ca on intestinal permeability.

PMID- 21851757
TI  - Chronic dietary intake of alpha-linolenic acid does not replicate the effects of
      DHA on passive properties of entorhinal cortex neurons.
AB  - n-3 PUFA are receiving growing attention for their therapeutic potential in
      central nervous system (CNS) disorders. We have recently shown that long-term
      treatment with DHA alters the physiology of entorhinal cortex (EC) neurons. In
      the present study, we investigated by patch-clamp the effect of another major
      dietary n-3 PUFA, alpha-linolenic acid (LNA), on the intrinsic properties of EC
      neurons. Mice were chronically exposed to isoenergetic diets deficient in n-3
      PUFA or enriched in either DHA or LNA on an equimolar basis. GC analyses revealed
      an increase in DHA (34%) and a decrease in arachidonic acid (AA, - 23%) in brain
      fatty acid concentrations after consumption of the DHA-enriched diet. Dietary
      intake of LNA similarly affected brain fatty acid profiles, but at a lower
      magnitude (DHA: 23%, AA: - 13%). Compared to the n-3 PUFA-deficient diet,
      consumption of DHA, but not LNA, induced membrane hyperpolarisation ( -60 to -70
      mV), increased cellular capacitance (32%) and spontaneous excitatory postsynaptic
      current frequency (50%). We propose that the inefficiency of LNA to modulate
      cellular capacitance was related to its inability to increase the brain DHA:AA
      ratio over the threshold necessary to up-regulate syntaxin-3 (46%) and
      translocate drebrin (40% membrane:cytosol ratio). In summary, our present study
      shows that the increase in brain DHA content following chronic administration of
      LNA was not sufficient to alter the passive and synaptic properties of EC
      neurons, compared to direct dietary intake of DHA. These diverging results have
      important implications for the therapeutic use of n-3 PUFA in CNS disease,
      favouring the use of preformed DHA.

PMID- 21851758
TI  - Clinical application of a micro multiplane transoesophageal probe in congenital
      cardiac disease.
AB  - AIM: To assess the quality of imaging modalities of a new micro multiplane
      transoesophageal echocardiogram probe. METHOD: This is a prospective study of
      micro transoesophageal echocardiogram S8-3t probe used at a single institution
      between 15 December, 2009 and 15 March, 2010. The images were compared with
      standard paediatric or adult probes where possible. Assessors prospectively rated
      imaging quality - two dimensional, colour flow imaging, pulse wave, and
      continuous wave Doppler - with a subjective 4-point scale (1 = poor to 4 =
      excellent). RESULTS: A total of 24 studies were performed on 23 patients, with a
      median weight = 11.7 kilograms (2.6-72 kilograms) and a median age of 3 years
      (0.16-60 years). Of the 23 patients, one neonate (2.8 kilograms) had transient
      bradycardia on probe insertion. Imaging in patients less than 10 kilograms was of
      full diagnostic value and new information was obtained in eight out of ten
      patients. Pulse wave and continuous wave Doppler was consistently good across all
      weight groups. There were high frame rates and good imaging quality to a depth of
      4-6 centimetres in all studies. A comparison with a larger alternative probe was
      available for 12 studies (weight 11.9-72 kilograms). The median micro
      transoesophageal two-dimensional image quality score was 3 (2-4) and 4 (3-4) with
      the comparative probe. For the 10- to 30-kilogram group, image quality with the
      micro transoesophageal echocardiogram probe was judged as inferior to larger
      standard probes. Adult sized patients had good imaging of near the field,
      allowing guidance for percutaneous device closure of the atrial septum.
      CONCLUSION: The micro multiplane transoesophageal echocardiogram probe provides
      imaging of diagnostic quality in neonates. In larger patients, it offers good
      imaging of near field structures. In the intermediate-sized child (10-30
      kilograms), standard paediatric probes provide better imaging.

PMID- 21851759
TI  - Cardiac magnetic resonance imaging predicts cardiac catheter findings for great
      artery stenosis in children with congenital cardiac disease.
AB  - OBJECTIVE: To assess the cardiac catheterisation findings of all children in whom
      cardiac magnetic resonance imaging found great artery stenosis. METHODS: We
      conducted a retrospective analysis of all 45 consecutive children with congenital
      cardiac disease who were undergoing cardiac catheterisation for intervention on
      cardiac magnetic resonance-defined great vessel stenosis, between January, 2006
      and August, 2008. RESULTS: Following cardiac magnetic resonance, 60 significant
      great vessel stenoses were identified and referred to cardiac catheterisation for
      intervention. All patients were catheterised within a median and interquartile
      range of 84 and 4-149 days, respectively, of cardiac magnetic resonance. At
      cardiac catheterisation, the children were aged 11.5 years - with an
      interquartile range of 3.8-16.9 years - and weighed 34 kilograms - with an
      interquartile range of 15-56 kilograms. Comparing cardiac magnetic resonance and
      cardiac catheterisation findings, 53 (88%) findings were concordant and seven
      were discordant. In six of seven (86%) discordant observations, cardiac magnetic
      resonance defined moderate-severe great vessel stenosis - involving three branch
      pulmonary arteries and three aortas. This was not confirmed by cardiac
      catheterisation, which revealed mild stenoses and haemodynamic gradients
      insufficient for intervention. In one patient, a mild, proximal right pulmonary
      artery narrowing was found at cardiac catheterisation, which was not mentioned in
      the cardiac magnetic resonance report. There was no difference between discordant
      and concordant groups on the basis of patient age, weight, interval between
      cardiac magnetic resonance and cardiac catheterisation, or type of lesion.
      CONCLUSION: Invasive assessment confirmed cardiac magnetic resonance-diagnosed
      great vessel stenosis in the majority of this cohort. The predominant discordant
      finding was lower catherisation gradient than predicted by morphologic and
      functional cardiac magnetic resonance assessment. Flow volume diversion - for
      example, unilateral pulmonary artery stenosis - and anaesthetic effects may
      account for some differences. Prospective refinement of cardiac magnetic
      resonance and interventional data may further improve the validity of non
      invasive imaging thresholds for intervention.

PMID- 21851760
TI  - Subcostal real-time three-dimensional echocardiography of interatrial
      communications: reconstruction of an oval fossa defect, a superior sinus venosus
      defect with partially anomalous pulmonary venous drainage, an infero-posterior
      oval fossa defect, and a coronary sinus defect.
AB  - Real-time three-dimensional echocardiography can surpass simple cross-sectional
      echocardiography in providing precise details of cardiac lesions. For the purpose
      of optimising treatment, we describe our findings with real-time three
      dimensional echocardiography when interrogating different types of communications
      permitting interatrial shunting. A three-dimensional reconstruction of defects
      within the oval fossa enabled reliable identification of location, size, and
      integrity of surrounding rims. In the superior sinus venosus defect associated
      with partially anomalous pulmonary venous drainage, three-dimensional
      reconstruction helped to provide a better understanding of the relationship
      between the interatrial communication, the orifice of the superior caval vein,
      and the connections of the right upper pulmonary vein. In the defect opening
      infero-posteriorly within the oval fossa, three-dimensional reconstruction helped
      to avoid the risk of potentially inappropriate closure of the defect by suturing
      the hyperplastic Eustachian valve to the atrial wall, which could have diverted
      the inferior caval venous return into the left atrium, or obstructed the caval
      venous orifice. In the coronary sinus defect, three-dimensional echocardiography
      provided a 'face to face' view of the entire coronary sinus roof, showing a
      circular defect communicating with the cavity of the left atrium. Acquisition of
      the full-volume data sets took less than 2 minutes for the patients having
      defects within the oval fossa, and no more than 3 minutes for the patients with
      the sinus venosus and coronary sinus defects. Post-processing for the defects in
      the oval fossa took from 5 to 8 minutes, and from 12 to 16 minutes for the more
      complicated defects. CONCLUSION: Cross-sectional two-dimensional echocardiography
      can establish correct diagnosis in all types of atrial communications; however,
      real-time three-dimensional reconstruction provides additional value to the
      surgeon and interventionist for better understanding of spatial intracardiac
      morphology.

PMID- 21851762
TI  - Barometer rising.

PMID- 21851761
TI  - Assessment of cardiac functions using tissue Doppler imaging in children with
      familial Mediterranean fever.
AB  - OBJECTIVE: Familial Mediterranean fever may carry a potential for cardiovascular
      disorders because of sustained inflammation during its course; however, there has
      been a limited number of studies investigating the cardiac functions in children.
      The aim of this study was to assess both ventricular diastolic functions using
      conventional echocardiography and tissue Doppler imaging in children with
      familial Mediterranean fever. PATIENTS AND METHODS: The study population included
      25 patients with familial Mediterranean fever - mean age was 11.8 plus or minus
      5.30 years - and 23 healthy patients as controls - mean age was 9.88 plus or
      minus 3.69 years. Both ventricular functions were measured using echocardiography
      comprising standard M-mode and conventional Doppler and tissue Doppler imaging
      during an attack-free period. RESULTS: The conventional echocardiographic
      parameters with myocardial performance index were in normal ranges and similar in
      patients with familial Mediterranean fever and controls, with a p-value more than
      0.05. However, right ventricular diastolic dysfunction was observed in patients
      with familial Mediterranean fever documented by tissue Doppler imaging, with a p
      value less than 0.05 for E't and A't wave ratio. CONCLUSION: Using tissue Doppler
      imaging, we have demonstrated that although left ventricular functions were
      comparable in the patients and healthy children, right ventricular diastolic
      function indices were impaired in patients with familial Mediterranean fever
      during childhood. Impaired right ventricular diastolic function may be an early
      manifestation of cardiac involvement in children with familial Mediterranean
      fever.

PMID- 21851763
TI  - Organelle transplantation should be legalized in Canada.

PMID- 21851764
TI  - Development and evaluation by a cluster randomised trial of a psychosocial
      intervention in children and teenagers experiencing diabetes: the DEPICTED study.
AB  - OBJECTIVE: To develop and evaluate a health-care communication training programme
      to help diabetes health-care professionals (HCPs) counsel their patients more
      skilfully, particularly in relation to behaviour change. DESIGN: The HCP training
      was assessed using a pragmatic, cluster randomised controlled trial. The primary
      and secondary analyses were intention-to-treat comparisons of outcomes using
      multilevel modelling to allow for cluster (service) and individual effects, and
      involved two-level linear models. SETTING: Twenty-six UK paediatric diabetes
      services. PARTICIPANTS: The training was delivered to HCPs (doctors, nurses,
      dietitians and psychologists) working in paediatric diabetes services and the
      effectiveness of this training was measured in 693 children aged 4-15 years and
      families after 1 year (95.3% follow-up). INTERVENTIONS: A blended learning
      programme was informed by a systematic review of the literature, telephone and
      questionnaire surveys of professional practice, focus groups with children and
      parents, experimental consultations and three developmental workshops involving a
      stakeholder group. The programme focused on agenda-setting, flexible styles of
      communication (particularly guiding) and a menu of strategies using web-based
      training and practical workshops. MAIN OUTCOME MEASURES: The primary trial
      outcome was a change in glycosylated haemoglobin (HbA1c) levels between the start
      and finish of a 12-month study period. Secondary trial outcomes included change
      in quality of life, other clinical [including body mass index (BMI)] and
      psychosocial measures (assessed at participant level as listed above) and cost
      (assessed at service level). In addition, patient details (HbA1c levels, height,
      weight, BMI, insulin regimen), health service contacts and patient-borne costs
      were recorded at each clinic visit, along with details of who patients consulted
      with, for how long, and whether or not patients consulted on their own at each
      visit. Patients and carers were also asked to complete an interim questionnaire
      assessing patient enablement (or feelings towards clinic visit for younger
      patients aged 7-10 years) at their first clinic visit following the start of the
      trial. The cost of the intervention included the cost of training intervention
      teams. RESULTS: Trained staff showed better skills than control subjects in
      agenda-setting and consultation strategies, which waned from 4 to 12 months.
      There was no effect on HbA1c levels (p = 0.5). Patients in intervention clinics
      experienced a loss of confidence in their ability to manage diabetes, whereas
      controls showed surprisingly reduced barriers (p = 0.03) and improved adherence
      (p = 0.05). Patients in intervention clinics reported short-term increased
      ability (p = 0.04) to cope with diabetes. Parents in the intervention arm
      experienced greater excitement (p = 0.03) about clinic visits and improved
      continuity of care (p = 0.01) without the adverse effects seen in their
      offspring. The mean cost of training was L13,145 per site or L2163 per trainee.
      There was no significant difference in total NHS costs (including training)
      between groups (p = 0.1). CONCLUSIONS: Diabetes HCPs can be trained to improve
      consultation skills, but these skills need reinforcing. Over 1 year, no benefits
      were seen in children, unlike parents, who may be better placed to support their
      offspring. Further modification of this training is required to improve outcomes
      that may need to be measured over a longer time to see effects. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN61568050. FUNDING: This project was
      funded by the NIHR Health Technology Assessment programme and will be published
      in full in Health Technology Assessment; Vol. 15, No. 29. See the HTA programme
      website for further project information.

PMID- 21851765
TI  - Teacher training in sexuality education in Australia: how well are teachers
      prepared for the job?

PMID- 21851766
TI  - Behavioural surveillance among gay men in Australia: methods, findings and policy
      implications for the prevention of HIV and other sexually transmissible
      infections.
AB  - BACKGROUND: The Australian HIV and sexually transmissible infection (STI)
      behavioural surveillance system (the repeated cross-sectional Gay Community
      Periodic Surveys, GCPS) has been conducted since 1998 and covers six main
      Australian jurisdictions. In this paper, we review its history and methodology,
      and the available indicators, their trends and their use. METHODS: We describe
      the design and history of GCPS. For analyses of indicators, we use Pearson's chi2
      test and test for trend where appropriate. RESULTS: About 90% of gay men in
      Australia have been tested for HIV (60% to 70% of men who were not HIV-positive)
      have been tested as recommended in the preceding 12 months. STI testing levels (~
      70% in the preceding 12 months) are high, but remain insufficient for STI
      prevention. In general, unprotected anal intercourse with regular (UAIR) and
      casual (UAIC) sex partners has increased over time. The prevalence and increasing
      trends in UAIR were similar across jurisdictions (P-trend <0.01), while trends in
      UAIC differed across the states: during 2001-08, UAIC declined in NSW (P-trend
      <0.01) and increased elsewhere (P-trend <0.01). Trends in UAIC were associated
      with HIV diagnoses. CONCLUSION: This review of the design, implementation and
      findings of the Australian HIV/STI behavioural surveillance highlights important
      lessons for HIV/STI behavioural surveillance among homosexual men, particularly
      the need for consistent data collection over time and across jurisdictions.
      Investment in systematic behavioural surveillance appears to result in a better
      understanding of the HIV epidemic, the availability of a warning system and a
      better targeted HIV prevention strategy.

PMID- 21851767
TI  - Treatment for prevention of HIV transmission in a localised epidemic: the case
      for South Australia.
AB  - BACKGROUND: Discussion is currently taking place among international HIV/AIDS
      groups around increasing HIV testing and initiating earlier use of antiretroviral
      therapy (ART) among people diagnosed with HIV as a method to reduce the spread of
      HIV. In this study, we explore the expected epidemiological impact of this
      strategy in a small population in which HIV transmission is predominantly
      confined to men who have sex with men (MSM). METHODS: A deterministic
      mathematical transmission model was constructed to investigate the impacts of
      strategies that increase testing and treatment rates, and their likely potential
      to mitigate HIV epidemics among MSM. Our novel model distinguishes men in the
      population who are more easily accessible to prevention campaigns through
      engagement with the gay community from men who are not. This model is applied to
      the population of MSM in South Australia. RESULTS: Our model-based findings
      suggest that increasing testing rates alone will have minimal impact on reducing
      the expected number of infections compared to current conditions. However, in
      combination with increases in treatment coverage, this strategy could lead to a
      59-68% reduction in the number of HIV infections over the next 5 years. Targeting
      men who are socially engaged with the gay community would result in the majority
      of potential reductions in incidence, with only minor improvements possible by
      reaching all other MSM. CONCLUSIONS: Investing in strategies that will achieve
      higher coverage and earlier initiation of treatment to reduce infectiousness of
      HIV-infected individuals could be an effective strategy for reducing incidence in
      a population of MSM.

PMID- 21851768
TI  - Triple class experience after initiation of combination antiretroviral treatment
      in Australia: survival and projections.
AB  - BACKGROUND: Patients who have become triple class experienced (TCE) are at a high
      risk of exhausting available treatment options. This study aims to investigate
      factors associated with becoming TCE and to explore the effect of becoming TCE on
      survival. We also project the prevalence of TCE in Australia to 2012. METHODS:
      Patients were defined as TCE when they stopped a combination antiretroviral
      treatment (cART) that introduced the third of the three major antiretroviral
      classes. Cox proportional hazards models were used to investigate factors
      associated with TCE and the effect of TCE on survival. To project TCE prevalence,
      we used predicted rates of TCE by fitting a Poisson regression model, together
      with the estimated number of patients who started cART in each year in Australia,
      assuming a mortality rate of 1.5 per 100 person-years. RESULTS: Of the 1498
      eligible patients, 526 became TCE. Independent predictors of a higher risk of TCE
      included current CD4 counts below 200cellsMUL(-1) and earlier calendar periods.
      No significant difference in survival was observed between those who were TCE and
      those who were not yet TCE. An increasing number of patients are using cART in
      Australia and if current trends continue, the number of patients who are TCE is
      estimated to increase from 2800 in 2003 to 5000 in 2012. CONCLUSION: Our results
      suggest that the prevalence of TCE in Australia is estimated to plateau after
      2003. However, as an increasing number of patients are becoming TCE, it is
      necessary to develop new drugs that come from new classes or do not have
      overlapping resistance.

PMID- 21851769
TI  - Increasing HIV diagnoses in Australia among men who have sex with men correlated
      with the growing number not taking antiretroviral therapy.
AB  - BACKGROUND: Australia has experienced rising notifications of HIV diagnoses
      despite widely available combination antiretroviral therapy (CART). New HIV
      diagnoses have also been younger than the average age of those living with HIV.
      We investigated the degree to which several risk factors could explain this rise
      in notifications and the younger age profile. METHODS: Numbers and ages of men
      who have sex with men (MSM) living with HIV in Australia from 1983 to 2007 were
      calculated from notifications of HIV diagnoses and deaths. We compared the trend
      over time as well as the average ages of MSM newly diagnosed with HIV infection
      from 1998 to 2007 with those for: notifications of gonorrhoea and syphilis, total
      MSM living with HIV infection, and the component not on CART. RESULTS: The
      percentage of younger MSM not taking CART has increased since 1998 (aged <30
      years P<0.001; 30-39 years P=0.004). The trend of new HIV diagnoses was most
      significantly correlated with the total number of MSM living with HIV infection
      and the sector not taking CART (P<0.0001). Based on similarity of average ages,
      MSM living with HIV infection and not taking CART was the best predictor of the
      increasing trend in new HIV diagnoses (99.9999% probability, Akaike information
      criterion). CONCLUSIONS: Our analyses suggest MSM living with HIV infection and
      not taking CART could be the source of the increase in HIV infections.
      Consequently, greater CART enrolment should decrease HIV incidence, especially in
      younger MSM.

PMID- 21851770
TI  - Increase in HIV diagnoses among men who have sex with men in New Zealand from a
      stable low period.
AB  - OBJECTIVES: To describe trends in HIV diagnoses among men who have sex with men
      (MSM) in New Zealand 1996-2008, and to identify characteristics associated with
      HIV diagnoses in the resurgent phase. METHODS: Data collected through routine
      surveillance of HIV infection, where the mode of transmission included homosexual
      contact, were analysed over the period 1996-2008. RESULTS: Annual HIV diagnoses
      were low during 1996-2000, rose sharply between 2001 and 2005, and remained at an
      elevated plateau between 2006 and 2008. Over a quarter were attributed to HIV
      infection acquired overseas (28.6%). Trends in diagnoses of locally acquired HIV
      infection closely mirrored the trend of three diagnosis phases. Increases in
      locally acquired HIV occurred among virtually all characteristics of MSM.
      However, compared with MSM diagnosed in the low phase 1996-2000, individuals
      diagnosed in the resurgent phase 2001-05 were more likely to be aged 30-39, to
      have tested HIV-negative within the previous 2 years, to live in the Northern
      region encompassing Auckland, and to be of non-European ethnicity. The per capita
      HIV diagnosis rate among MSM was lowest in 1997, at 22.0 per million males aged
      15-64, and highest in 2005 at 66.7 per million. CONCLUSION: The increase in HIV
      diagnoses among MSM in New Zealand was primarily due to an increase in locally
      acquired HIV infection, which disproportionately affected some groups of MSM.
      Factors driving this change in local epidemic conditions need to be identified.
      The rate of new HIV diagnoses among MSM remains low by international standards.

PMID- 21851771
TI  - Risk factors for HIV seroconversion in men who have sex with men in Victoria,
      Australia: results from a sentinel surveillance system.
AB  - OBJECTIVES: HIV diagnosis rates in men who have sex with men (MSM) began
      increasing in Australia 10 years ago, and there has been a major resurgence of
      syphilis. We determined predictors of HIV positivity and seroconversion among MSM
      in Victoria, Australia. METHODS: We conducted a retrospective longitudinal
      analysis of data from MSM who underwent HIV testing between April 2006 and June
      2009 at three primary care clinics. Logistic regression was used to determine
      predictors of HIV positivity and seroconversion. RESULTS: During the study
      period, 7857 MSM tested for HIV. Overall HIV positivity was 1.86% (95% confidence
      interval (CI): 1.6-2.2). There were 3272 repeat testers followed for 4837 person
      years (PY); 60 seroconverted and HIV incidence was 1.24 (95% CI: 0.96-1.60) per
      100 PY. Independent predictors of HIV seroconversion were: an infectious syphilis
      diagnosis within the last 2 years (adjusted hazard ratio (AHR)=2.5, 95% CI: 1.1
      5.7), reporting six or more anal sex partners in the past 6 months (AHR=3.3, 95%
      CI: 1.8-6.3), reporting an HIV-positive current regular partner (AHR=3.4, 95% CI:
      1.1-10.6) and reporting inconsistent condom use with casual partners in the past
      6 months (AHR=4.4, 95% CI: 1.7-11.5). CONCLUSION: Our results call for HIV
      prevention to target high-risk MSM, including men with a recent syphilis
      diagnosis or a high numbers of partners, men who have unprotected anal sex with
      casual partners and men in serodiscordant relationships. The HIV incidence
      estimate will provide a baseline to enable public health officials to measure the
      effectiveness of future strategies.

PMID- 21851772
TI  - The importance of social norms for uptake of catch-up human papillomavirus
      vaccination in young women.
AB  - BACKGROUND: Human papillomavirus (HPV) is the cause of almost all cases of
      cervical cancer. The current UK government immunisation program includes free
      routine HPV vaccination of girls aged 12-13, with a catch-up vaccination program
      for 13-18-year-old girls. The aim of this study was to identify correlates of
      intended and actual uptake of catch-up HPV vaccination. METHODS: An online
      questionnaire was completed by 591 young women aged 16-20. RESULTS: Of the 350
      women who had been offered catch-up HPV vaccination, 90.6% had accepted. In
      multivariate analyses, vaccine uptake was significantly correlated with
      subjective norms more supportive of HPV vaccination, and greater uptake of other
      childhood vaccinations (chi2(3))=39.34, P<0.01; 91.1% correctly classified;
      Nagelkerke pseudo-r2=0.23). Among the 241 women aged 16-20 who had not been
      offered HPV vaccination, the average intention was 3.70 on a five-point scale.
      Multivariate analyses revealed four significant independent predictors of
      stronger intentions to accept vaccination: subjective norms more supportive of
      HPV vaccination, greater worry about sexually transmissible infections, greater
      support for young people's sexual health services and greater support for
      childhood vaccination (F((4,236))=18.67, P<0.01; adjusted r2=0.23). Young women
      rated television advertisements, educational programs and television soaps as the
      most effective ways to encourage uptake of HPV vaccination. CONCLUSIONS: Uptake
      of HPV vaccination may be increased if interventions use appropriate media to
      promote social norms supportive of HPV vaccination.

PMID- 21851773
TI  - Human papillomavirus genotype prevalence in cervical biopsies from women
      diagnosed with cervical intraepithelial neoplasia or cervical cancer in Fiji.
AB  - BACKGROUND: There is currently limited information about human papillomavirus
      (HPV) genotype distribution in women in the South Pacific region. This study's
      objective was to determine HPV genotypes present in cervical cancer (CC) and
      precancers (cervical intraepithelial lesion (CIN) 3) in Fiji. METHODS: Cross
      sectional analysis evaluated archival CC and CIN3 biopsy samples from 296 women
      of Melanesian Fijian ethnicity (n=182, 61.5%) and Indo-Fijian ethnicity (n=114,
      38.5%). HPV genotypes were evaluated using the INNO-LiPA assay in archival
      samples from CC (n=174) and CIN3 (n=122) among women in Fiji over a 5-year period
      from 2003 to 2007. RESULTS: Overall, 99% of the specimens tested were HPV DNA
      positive for high-risk genotypes, with detection rates of 100%, 97.4% and 100% in
      CIN3, squamous cell carcinoma (SCC) and adenosquamous carcinoma biopsies,
      respectively. Genotypes 16 and 18 were the most common (77%), followed by HPV 31
      (4.3%). Genotype HPV 16 was the most common identified (59%) in CIN3 specimens,
      followed by HPV 31 (9%) and HPV 52 (6.6%). Multiple genotypes were detected in
      12.5-33.3% of specimens, depending on the pathology. CONCLUSION: These results
      indicated that the two most prevalent CC-associated HPV genotypes in Fiji
      parallel those described in other regions worldwide, with genotype variations
      thereafter. These data suggest that the currently available bivalent and
      quadrivalent HPV vaccines could potentially reduce cervical cancers in Fiji by
      over 80% and reduce precancers by at least 60%.

PMID- 21851774
TI  - Seroprevalence and correlates of hepatitis a among HIV-negative American men who
      have sex with men.
AB  - BACKGROUND: Hepatitis A outbreaks are well documented among men who have sex with
      men (MSM). This analysis examines characteristics associated with hepatitis A
      virus (HAV) infection among a large group of young adult MSM from five USA
      cities. METHODS: The Young Men's Survey was a cross-sectional prevalence study of
      HIV infection and related behavioural risk factors among MSM aged 15-29 years
      during 1994-2000. Serum specimens from HIV-negative participants were
      retrospectively tested for antibodies to HAV (anti-HAV). Data were stratified by
      ethnicity and analysed with logistic regression. RESULTS: Overall anti-HAV
      prevalence was 18.4% among the 2708 participants, and varied by ethnicity from
      6.9 to 45.3% and was highest among Hispanic and Asian men (P < 0.001). Prevalence
      increased with age across all racial/ethnic groups. Among white men, anti-HAV
      positivity was associated with having 20 or more lifetime male sex partners for
      those aged 15-22 years (adjusted odds ratio (AOR)=2.1, 95% confidence interval
      (CI)=1.0-4.1) and ever having had unprotected anal sex for those aged 23-29 years
      (AOR=2.4, 95% CI=1.2-4.5). CONCLUSIONS: Factors associated with a history of HAV
      infection among MSM in non-outbreak settings are probably similar to those among
      non-MSM. MSM are still at risk for HAV infection as a result of outbreaks
      occurring in MSM communities. Additional studies of hepatitis A vaccination
      coverage are needed to determine if strategies to vaccinate MSM are adequate.

PMID- 21851775
TI  - Sexual history taking and sexually transmissible infection screening practices
      among men who have sex with men: a survey of Victorian general practitioners.
AB  - BACKGROUND: HIV notifications among men who have sex with men (MSM) in Victoria,
      Australia, have increased recently. Early HIV diagnosis is a prevention strategy
      that requires general practitioners (GP) to recognise at-risk individuals and
      perform screening. Sexual history taking is part of this process. METHODS: A
      cross-sectional survey of 354 Victorian GP to investigate attitudes and practices
      regarding sexual history taking and screening for HIV in MSM. RESULTS: In total,
      185 (53%, 95% CI: 47-58%) GPs reported being 'very likely' to take a sexual
      history from MSM presenting for a routine check-up; however 161 (46%, 95% CI: 40
      51%) would not do so during the initial consultation. Barriers to sexual history
      taking included time constraints (28%, 95% CI: 24-36%), feeling inadequately
      trained (25%, 95% CI: 21-30%), discomfort discussing sex (24%, 95% CI: 20-29%)
      and fear of patient embarrassment (24%, 95% CI: 20-29%). Factors associated with
      a reduced likelihood included being male, time constraints, fear of patient
      embarrassment, and moral or religious views. Most GP (63%, 95% CI: 58-68%)
      reported they would offer HIV screening 3-6 monthly for MSM with casual partners;
      54 (16%, 95% CI: 12-20%) would offer screening only on request. Being unlikely to
      take a sexual history and fear of patient embarrassment were associated with a
      decreased likelihood of offering an HIV test. CONCLUSION: GP often fail to take a
      sexual history from MSM, limiting opportunities to offer HIV screening.
      Strategies are required to increase GPs' awareness of sexual health as a priority
      for MSM.

PMID- 21851776
TI  - Attitudes towards sex: a comparison of prisoners and the general community.
AB  - BACKGROUND: National population surveys of attitudes towards sexual issues
      typically exclude prisoners and little is known about their attitudes compared
      with the community. METHODS: Using computer-assisted telephone interviews, we
      compared a representative sample of 2289 prisoners (men=1960, women=329), aged 18
      59 years, from two Australian states against a national community sample of 6755
      participants (men=3333, women=3421). RESULTS: Overall, prisoners were slightly
      more conservative in their attitudes towards sex than the community. They were
      more likely than the community to agree with the statement that abortion is wrong
      (men: adjusted odds ratio (AOR)=3.3, 95% confidence interval (CI): 2.8-3.9;
      women: AOR=1.7, 95% CI: 1.2-2.4) and that male homosexuality is wrong (men:
      AOR=2.6, 95% CI: 2.2-3.1; women: AOR=1.7, 95% CI: 1.2-2.3); these differences
      were more pronounced for men than women. The attitudes of prisoners and the
      community varied with age. Attitudinal differences between prisoners and the
      community tended to be larger than the differences between women and men (agree
      that abortion is wrong: prisoners, AOR=0.5, 95% CI: 0.4-0.7; community, AOR=0.8,
      95% CI: 0.7-0.9; agree that male homosexuality is wrong: prisoners, AOR=0.4, 95%
      CI: 0.3-0.5; community, AOR=0.6, 95% CI: 0.5-0.7). CONCLUSION: Prisoners have
      either similar or less accepting attitudes towards sex than the general
      population. These attitudes contrast with the higher engagement in risk
      behaviours reported by prisoners.

PMID- 21851778
TI  - Condoms and US college-aged men and women: briefly assessing attitudes toward
      condoms and general condom use behaviours.
AB  - BACKGROUND: The purpose of this study was to develop an abbreviated reliable tool
      for assessing the attitudes US college-aged men and women have about condoms and
      condom use. METHOD: An online questionnaire was constructed and completed by 674
      participants incorporating modified items from the Attitudes Towards Condom Scale
      (1984) and the Multidimensional Condom Attitude Scale (1994), with the addition
      of gender-neutral worded and condom positive or erotic items. RESULTS: The
      original 40 items were reduced to 18 Likert-type items comprising the Brief
      Condom Attitude Scale (BCAS). Gender comparisons on a subset of 584 self
      identified heterosexual participants indicated that women were significantly more
      likely to consider condoms as less protective, while men were significantly more
      likely to consider condoms as more interruptive. Additional analyses examining
      partnership indicated that monogamous participants were significantly more likely
      to view condoms as less interruptive, more erotic and less negative than non
      monogamous participants. CONCLUSIONS: The BCAS appears to be a reliable measure
      for assessing US college-aged individuals' attitudes about condoms.

PMID- 21851777
TI  - Religion versus ethnicity as predictors of unprotected vaginal intercourse among
      young adults.
AB  - BACKGROUND: Young adults in North America are at increasing risk for contracting
      HIV and sexually transmissible infections (STI). Racial differences in HIV or STI
      risk are well documented, but other cultural and demographic factors contributing
      to HIV or STI risk are poorly understood. Although religion may play an important
      role in sexual behaviour, little research has explored its association with
      sexual attitudes, beliefs and practices. The present study examined how
      ethnicity, religion, HIV knowledge and attitudes, and other demographic factors
      are associated with engaging in unprotected vaginal intercourse (UVI) in a
      diverse sample of unmarried young adults. METHODS: A cross-sectional study of 666
      unmarried university students was conducted from 2005 to 2007, with participants
      completing an anonymous questionnaire on sexual attitudes and health for course
      credit. RESULTS: Approximately 50% of the respondents had engaged in any vaginal
      intercourse and 32.2% had engaged in UVI in the past 6 months. Multivariable
      analyses showed that increasing age, being in a relationship for more than 6
      months, greater HIV knowledge, stronger attitudes supporting the use of condoms,
      and religion (but not ethnicity) were associated with engaging in UVI. Among the
      sexually active subset of the sample (n=332), religion was the only predictor of
      engaging in UVI. CONCLUSION: Ethnicity, which is often considered an important
      variable in sexual health research, does not appear to be associated with UVI
      when taking into account other demographic variables, particularly religion.
      Consideration of religion may be important in devising HIV prevention
      interventions, in order to implement them in accordance with particular religious
      beliefs.

PMID- 21851779
TI  - Safer sex and condom use: a convenience sample of Aboriginal young people in New
      South Wales.
AB  - BACKGROUND: This paper examines condom use in a sample of Aboriginal young people
      in New South Wales (NSW) aged 16-30 years. METHODS: Cross-sectional data were
      collected using hand-held computer devices from 293 Aboriginal people attending
      two Aboriginal events in NSW. RESULTS: Almost two-thirds of respondents reported
      having had a casual sex partner in the previous 6 months. Of these, 39.2%
      reported always using a condom with casual partners. Having always used a condom
      with casual partners varied among respondents, and was more likely among younger
      respondents (adjusted odds ratio (AOR): 2.7, 95% confidence interval (CI): 1.2
      6.1) and less likely among those who used illicit drugs (AOR: 0.2, 95% CI: 0.1
      0.7). CONCLUSIONS: In comparison to published studies of other Australians,
      casual sex appears to be more common among this sample of Aboriginal young
      people; however, the proportion who report having always used condoms with casual
      partners is very similar. This suggests that although casual sex is more common,
      Aboriginal young people do not engage in risky behaviour any more often than
      other young Australians. Further work should be conducted with those who do not
      always use condoms, such as those who are older and who use illicit drugs,
      particularly with regards to how abstinence from drug use supports protective
      behaviours such as condom use among this population of Aboriginal young people.

PMID- 21851780
TI  - Is anal sex a marker for sexual risk-taking? Results from a population-based
      study of young Croatian adults.
AB  - BACKGROUND: There is evidence that anal sex is becoming increasingly popular
      among heterosexual women and men. Several studies carried out in especially
      vulnerable populations (e.g. sex workers and low-income youth) suggested that
      anal sex may indicate a more general propensity to sexual risk-taking. METHODS:
      To assess whether this epidemiologically important finding holds in the case of
      young adults from the general population, we analysed data from a cross-sectional
      probability survey carried out in 2010 on 1005 Croatian women and men aged 18-25.
      RESULTS: Anal intercourse was reported by 36.5% of 861 sexually experienced
      participants (42.7% of men and 29.8% of women). About one-third of them (34%)
      used a condom at most recent anal intercourse. The experience of anal sex was
      significantly associated (P<0.001) with all four indicators of sexual risk-taking
      (condom use at most recent vaginal intercourse, number of sexual partners in the
      past year, concurrent sexual relationships and anonymous sex in the past year),
      as well as with negative attitudes and beliefs about condom use (P<0.01). Sexual
      sensation-seeking mediated the relationship between anal sex and some of the
      sexual risk-taking behaviours. CONCLUSION: According to the findings,
      heterosexual anal sex is directly and indirectly associated with increased
      behavioural risks of acquiring HIV and other sexually transmissible infections
      (STI). Sex education and STI prevention programs should focus on the importance
      of using protection when practicing anal sex.

PMID- 21851781
TI  - Psychosocial pathways to inconsistent condom use among male sex workers:
      personality, drug misuse and criminality.
AB  - BACKGROUND: This research compared street male sex workers in Santo Andre,
      Brazil, that reported consistent condom use with those that revealed inconsistent
      condom use with their clients, concerning personality aspects, impulsiveness,
      alcohol and drug consumption, depressive symptoms, sociodemographic data and
      criminal involvement. METHODS: Eighty-six male sex workers were evaluated in face
      to-face interviews at their place of work. A 'snowball' sampling procedure was
      used to access this hard-to-reach population. FINDINGS: Male sex workers with
      inconsistent condom use showed greater involvement with criminal activities,
      higher reward dependence level and more frequent self-report of being HIV
      positive. CONCLUSIONS: Conceptualisation of male sex workers' psychological
      characteristics may be required where HIV risk is not only attributed to sex work
      per se, but to other aspects such as personality-related factors and negative
      identity.

PMID- 21851782
TI  - How likely are HIV-positive female sex workers in China to transmit HIV to
      others?
AB  - BACKGROUND: Female sex workers (FSW) are highly marginalised and HIV-positive FSW
      are under a double stigma. No study has assessed the likelihood of secondary
      transmission via HIV-positive FSW in China. METHODS: A total of 199 FSW who
      injected drugs were recruited by snowball sampling, and 158 non-injecting FSW
      were recruited from sex service establishments by convenience sampling in Dazhou,
      China. All participants were interviewed anonymously using a structured
      questionnaire. RESULTS: If found to be HIV-positive, 11.7% of the participants
      would continue working as FSW, 24.6% would not care about transmitting HIV to
      others, 18.8% believed that they would eventually spread HIV to others and 9%
      would take revenge by spreading HIV to others. In multivariate models, factors
      associated with >= 1 of the four aforementioned perceptions (42.0%) included drug
      use (odds ratio (OR)=1.82-3.26, P<0.01), perceived discrimination towards people
      living with HIV and AIDS in China (OR=2.03, P<0.05) and perceived inaccessibility
      to medical treatments if diagnosed as HIV-positive (OR=2.30, P<0.01); the reverse
      was true for use of HIV-related services (OR=0.53, P<0.05) and suicidal
      intentions if found to be HIV-positive (OR=0.42, P<0.05). CONCLUSIONS:
      Improvement of the social, care and medical environment of HIV-positive FSW is
      likely to reduce secondary transmission via HIV-positive FSW. Special attention
      should be given to FSW who inject drugs.

PMID- 21851783
TI  - Advertising sexual health services that provide sexually transmissible infection
      screening for rural young people - what works and what doesn't.
AB  - BACKGROUND: 'TESTme' is a sexually transmissible infection (STI) screening
      service for Victorian young people living in rural areas. We evaluated the
      effectiveness of advertising for this service over an 11-month pilot period.
      METHODS: The advertising that was used included websites, a Facebook page,
      posters, flyers, business cards, wrist bands and professional development
      sessions for health nurses that occurred throughout the pilot period. We also
      used once-off methods including advertisements in newspapers, student diaries and
      short messages to mobile phones. RESULTS: Twenty-eight clients had a consultation
      through TESTme. Twenty found the service through health professionals, six
      through the Melbourne Sexual Health Centre (MSHC) web page, one through the
      Facebook page and one through the student diary. The total direct costs incurred
      by the centre for advertising were $20850. The advertising cost per client
      reached for each advertising method was $26 for health professionals, $80 for the
      MSHC web advertisement, $1408 for Facebook and $790 for the student diary. Other
      advertising methods cost $12248 and did not attract any clients. CONCLUSION:
      Advertising STI health services for rural young people would be best to focus on
      referrals from other health services or health care websites.

PMID- 21851784
TI  - Trends of reported chlamydia infections and related complications in New Zealand,
      1998-2008.
AB  - AIM: To compare trends in chlamydia (Chlamydia trachomatis) testing and detection
      with trends in hospital discharge rates of chlamydia-related diseases in the
      upper North Island of New Zealand during 1998-2008. METHODS: Analysis of trends
      in chlamydia testing and detection rates and age-specific hospital admission
      rates per 100000 females for pelvic inflammatory disease (PID), female
      infertility and ectopic pregnancy, and per 100000 males for epididymo-orchitis.
      RESULTS: Regional laboratory testing volumes increased from 3732 tests per 100000
      population in 1998 to 9801 tests per 100000 in 2008. Two of three regions had a
      significant increase in percent test positivity over time. The highest detection
      rates and greatest increase in reported cases were amongst women aged 15-24
      years, at 1992 per 100000 in 1998, to 5737 per 100000 in 2008. For women aged 15
      24 years, the rate of hospital admissions for PID and chlamydia-related pelvic
      infections declined during 1998-2004 but rose in 2005-08, the rate of publicly
      funded infertility admissions fell and the ectopic pregnancy rate was unchanged.
      The age-specific rate for epididymo-orchitis admissions amongst 15-44-year-old
      men remained stable. CONCLUSION: Chlamydia testing volumes from three New Zealand
      regions have trebled since 1998, as have reported infection rates, although
      disease complication rates do not appear to have increased. Test positivity
      increases may reflect better targeted testing of those more at risk or a rising
      chlamydia incidence. The recent rise in hospital admissions for PID among women
      aged 15-24 is a concern; ongoing monitoring of these trends, despite data
      limitations, is important.

PMID- 21851785
TI  - Future chlamydia screening preferences of men attending a sexually transmissible
      infection clinic.
AB  - BACKGROUND: Despite years of public health efforts, Chlamydia trachomatis remains
      a highly prevalent disease suggesting that current control strategies are not
      sufficient. Asymptomatic men with chlamydial infections are under-identified and
      probably play an important role in sustaining the epidemic. Novel methods of
      actively screening asymptomatic men are needed to reduce the prevalence of
      chlamydia. This formative study explored the features of a sexually transmissible
      infection (STI) control program that would encourage annual testing among men.
      METHODS: Using semi-structured interviews and focus group discussions, we
      explored issues related to health seeking behaviours and preferences for STI
      screening among men recruited from a public health STI clinic. RESULTS: All 29
      participants acknowledged the expertise of clinic staff and most men preferred
      speaking with a provider over using electronic informational resources. The
      clinic was the preferred venue for future screening, followed by self-collected
      home sampling with clinic drop-off. Men expressed a preference for receiving
      results via the telephone rather than electronic options, and preferred
      personalised reminders for future STI screening. CONCLUSIONS: In this sample,
      there was high interest in utilising the expertise of STI clinic personnel and
      less in non-clinical options. While this may be due to recruiting from an STI
      clinic, the data serves as a reminder that service provision must be responsive
      to the needs of potential users. Our findings suggest that future non-clinic
      based screening strategies may require an initial educational component to
      address concerns about confidentiality and sample quality in order to be
      acceptable.

PMID- 21851786
TI  - Rectosigmoid vaginoplasty in patients with vaginal agenesis: sexual and
      psychosocial outcomes.
AB  - BACKGROUND: The main goal in women with Mayer-Rokitansky-Kuster-Hauser syndrome
      (vaginal agenesis) is creation of a neovagina that will satisfy the patient's
      desire. We evaluated sexual and psychosocial adjustment in patients who underwent
      rectosigmoid vaginoplasty because of vaginal agenesis. METHODS: A total of 36
      women, aged 21 to 38 years (mean=26) who underwent rectosigmoid vaginoplasty from
      1997 to 2006 were evaluated. Sexual and psychosocial appraisal included the
      Female Sexual Function Index (FSFI), Beck's Depression Inventory (BDI), and
      standardised questionnaires about postoperative satisfaction, social and sexual
      adjustment. RESULTS: Mean FSFI score was 28.9 (range=11.5-35.7) with a cut-off
      score of 26.55 for sexual dysfunction. Out of the 36 women, 10 (27, 8%) had
      sexual dysfunction. Mean BDI score was 7.55 (cut-off score=0-9 for non
      depression). Twenty-eight women (77.8%) were without symptoms of depression, six
      women (BDI range=10-29) had moderate and two women had severe depression
      (BDI=42). There were a significant number of patients (P<0.01) with a high
      satisfaction score in FSFI and low BDI results. Thirty-two (88.9%) of the
      patients believed that surgery was done at the right time and the main
      postoperative support came from their family. Thirty-four (94.4%) of the patients
      reported satisfactory femininity, with a heterosexual orientation. Thirty
      patients (83. 3%) were very satisfied with the surgery, while 34 considered
      surgery as the best treatment. CONCLUSIONS: The sexual function and psychosocial
      status of these patients should be followed long-term to estimate their quality
      of life.

PMID- 21851787
TI  - Increased risks of early sexual initiators: time makes a difference.
AB  - BACKGROUND: Years since onset of sexual intercourse (YSSI) is a rarely used
      variable when studying adolescents' sexual outcomes. The aim of this study is to
      evaluate the influence of YSSI on the adverse sexual outcomes of early sexual
      initiators. METHODS: Data were drawn from the 2002 Swiss Multicenter Adolescent
      Survey on Health database, a nationally representative cross-sectional survey
      including 7429 adolescents in post-mandatory school aged 16-20 years. Only
      adolescents reporting sexual intercourse (SI) were included (n=4388; 45% females)
      and categorised by age of onset of SI (early initiators, age <16: n=1469, 44%
      females; and late initiators, age >= 16: n=2919, 46% females). Analyses were done
      separately by gender. Groups were compared for personal characteristics at the
      bivariate level. We analysed three sexual outcomes (>= four sexual partners,
      pregnancy and condom non-use at last SI), controlling for all significant
      personal variables with two logistic regressions using first age, then YSSI as
      one of the confounding variables. Results are given as adjusted odds ratios (AOR)
      using late initiators as the reference category. RESULTS: After adjusting for
      YSSI instead of age, negative sexual outcomes among early initiators were no
      longer significant, except for multiple sexual partners among females, although
      at a much lower level. Early initiators were less likely to report condom non-use
      at last SI when adjusting for YSSI (females: AOR=0.59 [0.44-0.79], P<0.001;
      males: AOR=0.71 [0.50-1.00], P=0.053). CONCLUSION: YSSI is an important
      explanatory variable when studying adolescents' sexuality and needs to be
      included in future research on adolescents' sexual health.

PMID- 21851788
TI  - Premature labour precipitated by highly active antiretroviral therapy: an adverse
      reaction in a newly diagnosed HIV-positive patient.
AB  - A pregnant woman was diagnosed with HIV infection at 29 weeks' gestation.
      Antiretroviral therapy (ART) of lopinavir-ritonavir and zidovudine-lamivudine was
      initiated. Ten days later, a hypersensitivity reaction occurred, followed by
      preterm delivery of the infant 3 days later at 30 weeks' gestation.
      Hypersensitivity reactions to ART should prompt urgent consideration of a change
      in ART to avoid the potential for adverse pregnancy outcomes.

PMID- 21851789
TI  - The incidence of induced abortion in a prospective cohort study of 16- to 25-year
      old Australian women.
AB  - In Australia, data for induced abortions (IA) is unreliable, although accurate
      information is essential for the development of policy and funding for services
      relating to IA. The rate of induced abortion was an incidental finding from
      questionnaire data collected for a longitudinal study of chlamydia in young women
      in Australia. We found a pregnancy rate of 7.2/100 woman years (95% confidence
      interval (CI): 5.7-9.0) (n=76) and IA rate of 2.1/100 women years (95% CI: 1.4
      3.2) (n=22). Differences were found between States and Territories, information
      which might influence the development of services in regions of Australia.

PMID- 21851790
TI  - The first simultaneous study of the prevalence of Neisseria gonorrhoeae and
      Chlamydia trachomatis infections by polymerase chain reaction and standard
      methods.
AB  - BACKGROUND: Neisseria gonorrhoeae and Chlamydia trachomatis are important
      sexually transmissible pathogens. The aim of the present study was to determine
      their prevalence in symptomatic and asymptomatic people. METHODS: Polymerase
      chain reaction (PCR) and standard methods were tested for 413 specimens. RESULTS:
      The registered prevalence with PCR was N. gonorrhoeae 2.66% and C. trachomatis
      0.73%. One man showed co-infection. Standard methods demonstrated lower
      sensitivity in finding N. gonorrhoeae and C. trachomatis in comparison with the
      PCR. CONCLUSIONS: This is the first simultaneous study in Bulgaria for detection
      of N. gonorrhoeae and C. trachomatis by PCR and standard methods. N. gonorrhoeae
      was found to be a more frequent infection. Further investigations are needed.

PMID- 21851791
TI  - Detection of the sexually transmissible genital mycoplasmas by polymerase chain
      reaction in women.
AB  - BACKGROUND: The role of Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma
      genitalium in the development of clinical disorders is still unclear. The aim of
      this study was to determine their prevalence in symptomatic and asymptomatic
      women. METHODS: A total of 348 women were examined by applying polymerase chain
      reaction (PCR) methods. RESULTS: The registered prevalence was as follows: U.
      urealyticum 14.66%; M. hominis 3.16%; and M. genitalium 0.29%. Co-infection was
      established in 11 swabs. CONCLUSIONS: This is the first study in Bulgaria for the
      detection of mycoplasmas by PCR. Our results demonstrate similar or lower values
      in comparison with other researchers and further investigations are needed.

PMID- 21851792
TI  - [Precompetitive research, a synergy of public and private resources: for what
      purpose, how and in what framework?].

PMID- 21851793
TI  - Adaptive methods: when and how should they be used in clinical trials?
AB  - Adaptive clinical trial designs are defined as designs that use data cumulated
      during trial to possibly modify certain aspects without compromising the validity
      and integrity of the said trial. Compared to more traditional trials, in theory,
      adaptive designs allow the same information to be generated but in a more
      efficient manner. The advantages and limits of this type of design together with
      the weight of the constraints, in particular of a logistic nature, that their use
      implies, differ depending on whether the trial is exploratory or confirmatory
      with a view to registration. One of the key elements ensuring trial integrity is
      the involvement of an independent committee to determine adaptations in terms of
      experimental design during the study. Adaptive methods for clinical trials are
      appealing and may be accepted by the relevant authorities. However, the
      constraints that they impose must be determined well in advance.

PMID- 21851798
TI  - Impact of drugs on the environment: state of play, risks, evaluation,
      communication.
AB  - The aim of this Round Table was to perform an initial assessment of the state of
      play of the impact of drugs on the environment. Demographic growth throughout the
      world and drug consumption which is constantly on the increase result in an ever
      increasing presence of medicinal substances in the various compartments (air,
      water, soil) with potential repercussions on the environment and on health. For
      the first time, the Giens pharmacology workshop have scheduled this topic outside
      the conventional sphere of action of Giens. A very high level of interest in this
      topic came forward both from the members of the round table and the listeners and
      it is certain that the round table opens the door to new initiatives for a
      subject about which there is still little knowledge. The following issues were
      therefore successively addressed: the fragmentation of the knowledge about the
      subject and its deficiencies concerning the impact on health, both of the wastes
      as a whole and that of specific drugs, the performances of the water treatment
      methods, the sources of pollution, the environmental impact, the lines of
      regulatory development, the impact on the environment and health and the training
      programmes to be set up among all protagonists, both professional and in the
      general public.

PMID- 21851796
TI  - How to improve the clinical development paradigm and its division into phases I,
      II and III.
AB  - Based on the observation that over the last 30 years the cost of development has
      risen regularly as the number of new chemical entities reaching the market has
      fallen, how can "savings" be made in terms of clinical development, the objective
      being more rapid access to a drug for medical needs that are not covered? Several
      instruments exist to enable innovative products to be made available more
      quickly: temporary use authorisations, which are not concerned by this work
      (ATUs), conditional marketing authorisations (MAs) and MAs under exceptional
      circumstances. These aspects have been taken up in the European medicines agency
      (EMA)'s "Road Map", which states "A key issue for Regulators will be if a more
      "staggered" approval should be envisaged, characterised by a better defined/more
      restricted population of good responders, followed by a broadening of the
      population post-authorisation when more "real life" data are available. In
      addition, maximising the value of information generated in the post-authorisation
      phase should be developed through the use of cohorts and other prospectively
      collected use data, especially in the case of conditional marketing
      authorisations." The rules of procedure of the Transparency Commission for their
      part provide for the notion of preliminary examination: in order to prepare as
      best as possible the examination of dossiers of products assumed to be innovative
      and to limit delays, the office can undertake a preliminary study as soon as the
      dossier has been filed at the Committee for medicinal products for human use
      (CHMP). It may, at this time, request the firm to provide further information and
      may call on external experts. The implementation of this preliminary study does
      not exonerate the firm of the obligation of filing a complete dossier. The post
      inscription studies requested by the Transparency Commission (ISPEP - public
      health benefit and post-marketing studies) are usually requested in the case of
      hesitations regarding the level of improvement of the medical benefit (ASMR)
      [level II/III or IV/V]. Such requests mainly concern uncertainties regarding the
      transposability, the patient profile or correct usage in real life. Among the
      studies whose results were provided, in 15 cases the results were in line with
      expectations, in 6 cases they resulted in downward re-evaluations and the final 3
      cases were inconclusive. The final recommendations of the round table were:
      Defining the medical need that is not covered by working in consultation
      (Industry and Health Authorities); Providing a Complementary Investigations Plan
      (PIC) after the MA at a very early stage to reinforce the early MA, and/or HTA
      (health technology assessment) preparation and monitoring (possible constraining
      actions); Enhanced use of modelling techniques and their transposability;
      "Intussusception" of phases to optimise the development of a complete dossier;
      Early "scientific opinions" (EMA, French Health Products Safety Agency [Afssaps],
      French Health Authority [HAS]); Raising the awareness of the authorities,
      industry, doctors and patients with regard to controlled observational studies;
      Developing the use of public data bases.

PMID- 21851800
TI  - Role of the post-marketing authorisation studies in drug risk surveillance:
      specifications and methodologies.
AB  - Studies conducted after the marketing authorisation with the objective of
      identification, characterization or quantification of one or more risks (called
      PASS "Post-Authorisation Safety Studies"), have been strengthened in the past
      years with the implementation of the concept of risk management plans (RMPs),
      established in 2005 in the European regulatory framework and recently amended as
      part of the community revision. These safety studies, interventional or not, are
      related to a marketed drug, whether or not the drug is used within the market
      authorisation conditions. Apart from these safety studies, other studies whose
      primary objective is not risk assessment, including assessment of efficacy,
      description of prescription data and use in real life, pharmacokinetics, public
      health impact ... can complete available safety data.The Giens Round Table
      examined PASS from the risk management plans of a sample of marketing
      authorisation holders (participants to the Round Table) and identified the main
      characteristics of proposed actions. Concerning the specifications and the choice
      of methodology, only a general outline has been sketched in view of the
      complexity and diversity of drug risks situations.

PMID- 21851801
TI  - Knowledge and wishes of patients as regards vitamin K antagonists: a cross
      sectional survey in Western Brittany, France.
AB  - OBJECTIVE: We aimed to investigate patients' educational wishes and patients'
      perception of their knowledge of anticoagulants. MATERIAL AND METHODS: One
      thousand patients were randomly sampled from a list of patients living within the
      Brest district (France) affiliated to the National Health Insurance System and
      who had been reimbursed after the delivery of vitamin K antagonists in May 2007.
      A 56-item questionnaire has been mailed along with an information letter and a
      reply-paid envelope enclosed. RESULTS: Some 647 questionnaires were received; 82%
      of responders declared having been informed. Information was globally perceived
      as complete although alleged as being insufficient as regards bleeding
      management. Management of oral anticoagulants appears correct; however, only 28%
      of responders stated having a surveillance booklet; 63% of responders would like
      information and elicited oral information from their general practitioner.
      CONCLUSION: Our study highlighted the importance of general practitioners in the
      French health system when thinking about implementing an educational program on
      anticoagulation.

PMID- 21851802
TI  - Evolution of opioids reimbursement since 2004 from the National Database of the
      General Health Insurance System.
AB  - OBJECTIVE: This study aims at evaluating trends in the consumption of opioids
      over the last years to assess the impact of public health measures on the
      management of pain and opiate addiction in France. METHODS: The evolution of
      opioids consumption was analysed by using the national database of the General
      Health Insurance System in France between 2004 and 2008. RESULTS: During the
      study period, the reimbursed quantities of opioids used for pain management have
      increased by 13%, except for dextropropoxyphene that has decreased by 9%. The
      reimbursed quantities of opioids used for substitution maintenance treatments for
      opioid dependence have increased by 34%, with a 116% increase for methadone.
      CONCLUSION: This study suggests that consumption of opioids is globally
      increasing in France and reveals discrepancies concerning the evolution of the
      different drugs. It allows to analyse switches of consumption between different
      opioids and constitutes the first step for further studies targetting signals of
      diversion and abuse.

PMID- 21851803
TI  - Contributions from scientific research to the risk assessment of GMOs. Lessons
      learned from a symposium held in Brussels, Belgium, 21-22 October 2010.

PMID- 21851804
TI  - Suicide-related behaviors and anxiety in children and adolescents: a review.
AB  - This paper reviews empirical evidence of the association between suicide-related
      behaviors and anxiety among children and adolescents. It begins with a review of
      suicide-related behaviors and anxiety, discusses methodological issues related to
      measurement, and reviews empirical findings published since the last review of
      this topic in 1988. Evidence is summarized on four criteria necessary to
      establish anxiety as a causal risk factor for suicide-related behaviors among
      children and adolescents. There is consistent evidence for a significant
      association between anxiety and suicide-related behaviors (Criterion 1). Evidence
      that the influence of anxiety on suicide-related behaviors is not due to a third
      variable (Criterion 2) is mixed and hindered by methodological limitations. The
      literature is also unclear as to whether anxiety temporally precedes suicide
      related behaviors (Criterion 3). Finally, this review found no evidence to
      support or refute anxiety's stability independent of and across instances of
      suicide-related behaviors (Criterion 4). Theoretical and clinical implications of
      these findings and directions for future research are discussed.

PMID- 21851805
TI  - Understanding the nature and etiology of intimate partner violence and
      implications for practice and policy.
AB  - Theoretical perspectives underlying hypotheses about the nature and etiology of
      intimate partner violence are important as they inform professionals how they
      should best respond to reduce or eliminate this social problem. Therefore, it is
      crucial that practice led initiatives are driven by theory that is supported by
      good quality empirical evidence. This review aims to provide a synthesis of
      methodologically sound research to understand how intimate partner violence is
      best conceptualized, and what the implications of this evidence based theory hold
      for practice and policy. A wealth of evidence supporting the need to further
      explore and respond to the spectrum of partner violence from a gender inclusive
      perspective is demonstrated. Implications of the evidence for multidisciplinary
      work, prevention, assessment, treatment, and policy related to intimate partner
      violence are discussed.

PMID- 21851807
TI  - Artificial membrane-like environments for in vitro studies of purified G-protein
      coupled receptors.
AB  - Functional reconstitution of transmembrane proteins remains a significant barrier
      to their biochemical, biophysical, and structural characterization. Studies of
      seven-transmembrane G-protein coupled receptors (GPCRs) in vitro are particularly
      challenging because, ideally, they require access to the receptor on both sides
      of the membrane as well as within the plane of the membrane. However,
      understanding the structure and function of these receptors at the molecular
      level within a native-like environment will have a large impact both on basic
      knowledge of cell signaling and on pharmacological research. The goal of this
      article is to review the main classes of membrane mimics that have been, or could
      be, used for functional reconstitution of GPCRs. These include the use of
      micelles, bicelles, lipid vesicles, nanodiscs, lipidic cubic phases, and planar
      lipid membranes. Each of these approaches is evaluated with respect to its
      fundamental advantages and limitations and its applications in the field of GPCR
      research. This article is part of a Special Issue entitled: Membrane protein
      structure and function.

PMID- 21851806
TI  - Transforming growth factor-beta regulates the growth of valve interstitial cells
      in vitro.
AB  - Although valve interstitial cell (VIC) growth is an essential feature of injured
      and diseased valves, the regulation of VIC growth is poorly understood.
      Transforming growth factor (TGF)-beta promotes VIC proliferation in early-stage
      wound repair; thus, herein, we tested the hypothesis that TGF-beta regulates VIC
      proliferation under normal nonwound conditions using low-density porcine VIC
      monolayers. Cell numbers were counted during a 10-day period, whereas
      proliferation and apoptosis were quantified by bromodeoxyuridine staining and
      TUNEL, respectively. The extent of retinoblastoma protein phosphorylation and
      expression of cyclin D1, CDK 4, and p27 were compared using Western blot
      analysis. Adhesion was quantified using a trypsin adhesion assay, and
      morphological change was demonstrated by immunofluorescence localization of alpha
      smooth muscle actin and vinculin. TGF-beta-treated VICs were rhomboid;
      significantly decreased in number, proliferation, and retinoblastoma protein
      phosphorylation; and concomitantly had decreased expression of cyclin D1/CDK4 and
      increased expression of p27. TGF-beta-treated VICs adhered better to substratum
      and had more vinculin plaques and alpha-smooth muscle actin stress fibers than
      did controls. Thus, the regulation of VIC growth by TGF-beta is context
      dependent. TGF-beta prevents excessive heart valve growth under normal
      physiological conditions while it promotes cell proliferation in the early stages
      of repair, when increased VICs are required.

PMID- 21851808
TI  - Photo-dynamic induction of oxidative stress within cholesterol-containing
      membranes: shape transitions and permeabilization.
AB  - Photochemical internalization is a drug delivery technology employing a photo
      destabilization of the endosomes and the photo-controlled release of endocyted
      macromolecules into the cytosol. This effect is based on the ability of some
      photosensitizers to interact with endosomal membranes and to photo-induce damages
      leading to its breakdown. The permeabilization efficiency is not quantitatively
      related to the importance of the damages, but to their asymmetric repartition
      within the leaflets. Using unilamellar vesicles and a chlorin, we studied the
      effect of the membrane's cholesterol content on its photo-permeabilization.
      First, the affinity of the chlorin for membranes was studied. Then, we
      asymmetrically oxidized the membranes. For DOPC/CHOL GUVs, we observed different
      shape transitions, in accordance with an increase followed by a decrease of the
      membrane effective curvature. These modifications are delayed by the cholesterol.
      Finally, the photo-permeabilization of GUVs occurs, corresponding to a pore
      formation due to the membrane tension, resulting from vesicles buddings.
      Cholesterol-rich GUVs permeabilization occurs after a lag, and is less important.
      These results are interpreted regarding both (i) the cholesterol-induced
      tightening of the lipids, its consequences on physical parameters of the membrane
      and on oxidation rate and (ii) the suggested ability of cholesterol to flip
      rapidly and then to relax the differential density-based stress accumulated
      during membrane bending.

PMID- 21851811
TI  - Urinary monocyte chemoattractant protein-1 in renal disease.
AB  - Monocyte chemoattractant protein-1 (MCP-1/CCL2) has a critical role in the
      development of various renal diseases. Data from disease specific experimental
      animal models and clinical studies confirm that MCP-1 plays an important part in
      the pathogenesis of renal diseases. The action of MCP-1 in these studies has been
      shown to be more complex than the traditional concept of monocyte/macrophage
      recruitment to the inflammatory site. MCP-1 is expressed in renal tissues and it
      is detectable in urine of patients with a variety of renal diseases. Measurement
      of urinary levels of MCP-1 can provide valuable information not only for the
      diagnosis of active renal disease, but also for monitoring of response to
      therapy. Urinary MCP-1 measurement can provide help with evaluation of the
      prognosis in various renal diseases. Furthermore, selective targeting of MCP-1
      could be an effective treatment in suppressing a number of renal diseases as
      blocking MCP-1 has already been shown to ameliorate renal diseases in
      experimental animal models. The advantage of measuring urinary MCP-1 rather than
      the conventional markers must now be validated using a larger cohort of patients
      in different renal diseases. Also the therapeutic potential of MCP-1 targeting
      agents needs to be investigated in clinical studies.

PMID- 21851810
TI  - An ensemble dynamics approach to decipher solid-state NMR observables of membrane
      proteins.
AB  - Solid-state NMR (SSNMR) is an invaluable tool for determining orientations of
      membrane proteins and peptides in lipid bilayers. Such orientational descriptions
      provide essential information about membrane protein functions. However, when a
      semi-static single conformer model is used to interpret various SSNMR
      observables, important dynamics information can be missing, and, sometimes, even
      orientational information can be misinterpreted. In addition, over the last
      decade, molecular dynamics (MD) simulation and semi-static SSNMR interpretation
      have shown certain levels of discrepancies in terms of transmembrane helix
      orientation and dynamics. Dynamic fitting models have recently been proposed to
      resolve these discrepancies by taking into account transmembrane helix whole body
      motions using additional parameters. As an alternative approach, we have
      developed SSNMR ensemble dynamics (SSNMR-ED) using multiple conformer models,
      which generates an ensemble of structures that satisfies the experimental
      observables without any fitting parameters. In this review, various computational
      methods for determining transmembrane helix orientations are discussed, and the
      distributions of VpuTM (from HIV-1) and WALP23 (a synthetic peptide) orientations
      from SSNMR-ED simulations are compared with those from MD simulations and semi
      static/dynamic fitting models. Such comparisons illustrate that SSNMR-ED can be
      used as a general means to extract both membrane protein structure and dynamics
      from the SSNMR measurements. This article is part of a Special Issue entitled:
      Membrane protein structure and function.

PMID- 21851812
TI  - Interference in human chorionic gonadotropin (hCG) analysis by macro-hCG.

PMID- 21851809
TI  - Molecular simulations and solid-state NMR investigate dynamical structure in
      rhodopsin activation.
AB  - Rhodopsin has served as the primary model for studying G protein-coupled
      receptors (GPCRs)-the largest group in the human genome, and consequently a
      primary target for pharmaceutical development. Understanding the functions and
      activation mechanisms of GPCRs has proven to be extraordinarily difficult, as
      they are part of a complex signaling cascade and reside within the cell membrane.
      Although X-ray crystallography has recently solved several GPCR structures that
      may resemble the activated conformation, the dynamics and mechanism of rhodopsin
      activation continue to remain elusive. Notably solid-state ((2))H NMR
      spectroscopy provides key information pertinent to how local dynamics of the
      retinal ligand change during rhodopsin activation. When combined with molecular
      mechanics simulations of proteolipid membranes, a new paradigm for the rhodopsin
      activation process emerges. Experiment and simulation both suggest that retinal
      isomerization initiates the rhodopsin photocascade to yield not a single
      activated structure, but rather an ensemble of activated conformational states.
      This article is part of a Special Issue entitled: Membrane protein structure and
      function.

PMID- 21851813
TI  - Functional sensitivity of seven automated thyroid stimulating hormone
      immunoassays.
AB  - BACKGROUND: Serum thyroid stimulating hormone (TSH) measurements are useful for
      detecting clinical and subclinical primary hypo- and hyperthyroidism in
      ambulatory patients. For diagnosis of hyperthyroidism, the functional sensitivity
      (FS) is an important performance criterion, and current guidelines recommend an
      FS of <=0.02 m IU/l for "third" generation performance. METHODS: We evaluated TSH
      FS for the Access 2, Advia Centaur, Architect i2000, Dimension ExL Modular
      Analytics E170, Immulite 2000 and Dimension Vista 1500 automated immunoassays
      using serum pools tested over a 6 week period using 2 reagent lots and 2
      calibrations. FS was determined by fitting a power function to the imprecision
      data using KaleidaGraph software. RESULTS: The FS (m IU/l) for Access 2, ADVIA
      Centaur, ARCHITECT i2000, Dimension ExL, Modular Analytics E170, Immulite 2000,
      and Dimension Vista 1500 systems were determined to be 0.039, 0.006, 0.007,
      0.003, 0.008, 0.003, and 0.003, respectively. The lowest and next to lowest pools
      had overall mean TSH concentrations of 0.012 m IU/l and 0.020 m IU/l,
      respectively and a range of concentrations of 0.005 to 0.022 m IU/l and 0.007 to
      0.077 m IU/l, respectively. CONCLUSIONS: All assays showed excellent performance
      in FS consistent with a "third" generation claim except for the Access 2 system.
      Further harmonization of TSH immunoassays is required, especially at lower
      concentrations.

PMID- 21851814
TI  - A comprehensive HBV array for the detection of HBV mutants and genotype.
AB  - OBJECTIVE: To develop a comprehensive hepatitis B virus (HBV) array providing
      simultaneous analysis of 8 genotypes, 47 mutations of reverse-transcriptase
      polymerase gene and 18 mutations of S gene. METHOD: Oligonucleotides
      corresponding to various HBV-normal and -mutant sequences were spotted onto pre
      treated glass slides. Single-stranded templates of the HBV gene fragment were
      prepared from serum-DNA of HBV-infected patients by 2-staged PCR and subjected to
      allele-specific arrayed-primer extension with Cy5-dCTP. Fluorescein-labelled
      products were scanned at 670nm. RESULTS: Comparative analysis of 100 unrelated
      samples using the array and a commercial kit, revealed 44 with additional
      mutations from the array, these were confirmed by sequencing. Analysis of 381
      samples from 45 patients during 1-3 years of anti-viral therapy showed improved
      sensitivity with detection of drug-resistant mutations months before clinical
      relapse. The lower detection limit was 28 copies/mL. CONCLUSION: The array is
      better than many existing methods as it provides both mutations and genotype data
      in a single analysis.

PMID- 21851815
TI  - Cardiac troponin testing in the acute care setting: ordering, reporting, and high
      sensitivity assays--an update from the Canadian society of clinical chemists
      (CSCC).

PMID- 21851816
TI  - Fibroblasts from the muscles of Duchenne muscular dystrophy patients are
      resistant to cell detachment apoptosis.
AB  - Extracellular matrix (ECM) proteins, including collagen and growth factors, are
      greatly increased in tissue fibrosis and mainly secreted by fibroblasts. We
      previously demonstrated that muscle-derived fibroblasts from Duchenne muscular
      dystrophy (DMD) patients have a profibrotic phenotype, that includes
      significantly reduced expression of tissue inhibitor of metalloprotease 3 (TIMP
      3) compared to control. Since TIMP-3 induces apoptosis in various cell types, we
      hypothesized increased resistance of DMD fibroblasts to apoptosis. To address
      this, we evaluated apoptotic nuclei, caspase 3, caspase 3 substrate expression,
      and migration and adhesion properties of muscle-derived fibroblasts, after
      applying different apoptosis-inducing treatments. We found that DMD fibroblasts
      were less susceptible to cell death, more adhesive, and had greater tendency to
      migrate than control fibroblasts - findings further supported by alterations in
      FAK and ERK/MAPK expression. Resistance to apoptosis and greater adhesion are
      likely to contribute to muscle fibrosis so a pharmacological treatment that
      targets dysregulated pathways involved in cell detachment apoptosis (anoikis) may
      limit the progressive fibrotic remodeling characteristic of DMD.

PMID- 21851817
TI  - The lipid kinase PI4KIIIbeta and the eEF1A2 oncogene co-operate to disrupt three
      dimensional in vitro acinar morphogenesis.
AB  - The study of in vitro morphogenesis is fundamental to understanding neoplasia
      since the dysregulation of morphogenic pathways that create multi-cellular
      organisms is a common hallmark of oncogenesis. The in vitro culture of human
      breast epithelial cells on reconstituted basement membranes recapitulate some
      features of in vivo breast development, including the formation of a three
      dimensional structure termed an acinus. Importantly, the capacity to disrupt in
      vitro acinar morphogenesis is a common property of human breast oncogenes. In
      this report, we find that phosphatidylinositol 4-kinase IIIbeta (PI4KIIIbeta), a
      lipid kinase that phosphorylates phosphatidylinositol (PI) to PI(4)P, disrupts in
      vitro mammary acinar formation. The PI4KIIIbeta protein localizes to the basal
      surface of acini created by human MCF10A cells and ectopic expression of
      PI4KIIIbeta induces multi-acinar devlopment. Furthermore, expression of an
      oncogenic PI4KIIIbeta activator, eEF1A2 (eukaryotic elongation factor 1 alpha 2),
      phenocopies the PI4KIIIbeta multi-acinar phenotype. Ectopic expression of
      PI4KIIIbeta or eEF1A2 alters the localization of PI(4)P and PI(4,5)P(2) within
      acini, indicating the importance of these lipids in acinar development. Our work
      shows that PI4KIIIbeta, eEF1A2 and PI(4)P likely play an important role in
      mammary neoplasia and acinar development.

PMID- 21851818
TI  - Wnt/Myc interactions in intestinal cancer: partners in crime.
AB  - Loss of the APC (adenomatous polyposis coli) gene in colorectal cancer leads to a
      rapid deregulation of TCF/LEF target genes. Of all these target genes, the
      transcription factor c-MYC appears the most critical. In this review we will
      discuss the interplay of Wnt and c-MYC signaling during intestinal homeostasis
      and transformation. Furthermore, we will discuss recent data showing that further
      deregulation of c-MYC levels during colorectal carcinogenesis may drive tumor
      progression. Moreover, understanding these additional control mechanisms may
      allow targeting of c-MYC during colorectal carcinogenesis.

PMID- 21851819
TI  - alpha1-adrenergic drugs exhibit affinity to a thapsigargin-sensitive binding site
      and interfere with the intracellular Ca2+ homeostasis in human erythroleukemia
      cells.
AB  - Even though the erythroleukemia cell lines K562 and HEL do not express alpha1
      adrenoceptors, some alpha1-adrenergic drugs influence both survival and
      differentiation of these cell lines. Since Ca2+ is closely related to cellular
      homeostasis, we examined the capacity of alpha1-adrenergic drugs to modulate the
      intracellular Ca2+ content in K562 cells. Because of morphological alterations of
      mitochondria following alpha1-adrenergic agonist treatment, we also scrutinized
      mitochondrial functions. In order to visualize the non-adrenoceptor binding
      site(s) of alpha1-adrenergic drugs in erythroleukemia cells, we evaluated the
      application of the fluorescent alpha1-adrenergic antagonist BODIPY(r) FL
      Prazosin. We discovered that the alpha1-adrenergic agonists naphazoline,
      oxymetazoline and also the alpha1-adrenergic antagonist benoxathian are able to
      raise the intracellular Ca2+-content in K562 cells. Furthermore, we demonstrate
      that naphazoline treatment induces ROS-formation as well as an increase in
      Deltapsim in K562 cells. Using BODIPY(r) FL-Prazosin we were able to visualize
      the non-adrenoceptor binding site(s) of alpha1-adrenergic drugs in
      erythroleukemia cells. Interestingly, the SERCA-inhibitor thapsigargin appears to
      interfere with the binding of BODIPY(r) FL-Prazosin. Our data suggest that the
      effects of alpha1-adrenergic drugs on erythroleukemia cells are mediated by a
      thapsigargin sensitive binding site, which controls the fate of erythroleukemia
      cells towards differentiation, senescence and cell death through modulation of
      intracellular Ca2+.

PMID- 21851820
TI  - MUC6 mucin expression inhibits tumor cell invasion.
AB  - The MUC6 mucin has a critical protective function in the normal stomach, pancreas
      and duodenum and is aberrantly expressed during the progression of some
      gastrointestinal cancers. Our aim was to determine whether MUC6 contributes to
      the etiology or progression of pancreatic cancer and elucidate the molecular
      basis of its involvement. Expression of MUC6 glycoprotein was examined in
      pancreatic cancer tissues by immunofluorescence and loss of MUC6 was observed.
      Next, to determine whether MUC6 inhibits tumor growth and metastasis by altering
      cell adhesion and invasion, recombinant MUC6 cDNA and separate MUC6 N-terminal
      and C-terminal domains were transfected into pancreatic, colorectal and breast
      cancer cell lines. The recombinant N- and C-terminal proteins were each seen to
      oligomerize under non-reducing conditions. Overexpression of both domains of the
      MUC6 glycoprotein significantly inhibited cell adhesion to matrix proteins
      (collagen I, collagen IV, fibronectin and laminin) in LS 180 but not in PANC-1
      cells. Moreover, the N- and C-terminal domains of MUC6 inhibited invasion of both
      LS 180 and PANC-1 cells by 40% and 70%, respectively, in comparison with
      controls. These results suggest that MUC6 may inhibit invasion of tumor cells
      through the basement membrane of the pancreatic duct and slow the development of
      infiltrating carcinoma.

PMID- 21851821
TI  - Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal
      female prairie voles enhances alloparental responsiveness and partner preference
      formation as adults.
AB  - Oxytocin receptors (OXTR) in the nucleus accumbens (NAcc) promote alloparental
      behavior and partner preference formation in female prairie voles. Within the
      NAcc there is significant individual variation in OXTR binding and virgin
      juvenile and adult females with a high density of OXTR in the NAcc display an
      elevated propensity to engage in alloparental behavior toward novel pups. Over
      expression of OXTR in the NAcc of adult female prairie voles using viral vector
      gene transfer facilitates partner preference formation, but has no effect on
      alloparental behavior, even though OXTR antagonists infused into the NAcc blocks
      both behaviors. We therefore hypothesized that long-term increases in OXTR
      signaling during development may underlie the relationship between adult OXTR
      density in the NAcc and alloparental behavior. To test this hypothesis, we used
      viral vector gene transfer to increase OXTR density in the NAcc of prepubertal,
      21day old female prairie voles and tested for both alloparental behavior and
      partner preference formation as adults. Consistent with a developmental impact of
      OXTR signaling, adults over-expressing OXTR from weaning display both increased
      alloparental behavior and partner preference formation. Thus, the relatively
      acute impact of elevated OXTR signaling in the NAcc on partner preference
      formation previously reported appears to be dissociable from the effects of
      longer term, developmentally relevant OXTR signaling necessary for modulating
      alloparental behavior. These results are consistent with the hypothesis that
      oxytocin can have both long-term "organizational" effects as well as acute
      "activational" effects on affiliative behaviors.

PMID- 21851822
TI  - Short day lengths alter stress and depressive-like responses, and hippocampal
      morphology in Siberian hamsters.
AB  - Many psychological disorders comprise a seasonal component. For instance,
      seasonal affective disorder (SAD) is characterized by depression during autumn
      and winter. Because hippocampal atrophy may underlie the symptoms of depression
      and depressive-like behaviors, one goal of this study was to determine whether
      short days also induce structural changes in the hippocampus using photoperiod
      responsive rodents--Siberian hamsters. Exposure to short days increases
      depressive-like responses (increased immobility in the forced swim test) in
      hamsters. Male hamsters were housed in either short (LD 8:16) or long days (LD
      16:8) for 10 weeks and tested in the forced swim test. Brains were removed and
      processed for Golgi impregnation. HPA axis function may account for photoperiod
      related changes in depressive-like responses. Thus, stress reactivity was
      assessed in another cohort of photoperiod-manipulated animals. Short days reduced
      soma size and dendritic complexity in the CA1 region. Photoperiod did not induce
      gross changes in stress reactivity, but an acute stressor disrupted the typical
      nocturnal peak in cortisol concentrations. These data reveal that immobility
      induced by exposure to short days is correlated with reduced CA1 cell complexity
      (and perhaps connectivity). This study is the first to investigate hippocampal
      changes in the context of short-day induced immobility and may be relevant for
      understanding psychological disorders with a seasonal component.

PMID- 21851823
TI  - Defence behaviours of the praying mantis Tenodera aridifolia in response to
      looming objects.
AB  - Defence responses to approaching objects were observed in the mantis Tenodera
      aridifolia. The mantis showed three kinds of behaviour, fixation, evasion and
      cryptic reaction. The cryptic reaction consisted of rapid retraction of the
      forelegs under the prothorax or rapid extending of the forelegs in the forward
      direction. Obstructing the mantis' sight decreased its response rates, suggesting
      that the visual stimuli generated by an approaching object elicited the cryptic
      reaction. The response rate of the cryptic reactions was highest for objects that
      approached on a direct collision course. Deviation in a horizontal direction from
      the direct collision course resulted in a reduced response. The response rate of
      the cryptic reaction increased as the approaching velocity of the object
      increased, and the rate decreased as the object ceased its approach at a greater
      distance from the mantis. These results suggest that the function of the observed
      cryptic reactions is defence against impending collisions. The possible role of
      the looming-sensitive neuron in the cryptic reaction is also discussed.

PMID- 21851824
TI  - Where are the new drugs to treat heart failure? Introduction to the special issue
      on "key signaling molecules in hypertrophy and heart failure".

PMID- 21851825
TI  - Myocardial salvage in acute myocardial infarction--challenges in clinical
      translation.

PMID- 21851826
TI  - Sildenafil inhibits calcineurin/NFATc2-mediated cyclin A expression in pulmonary
      artery smooth muscle cells.
AB  - AIMS: To examine whether calcineurin/NFAT signaling pathway leads to
      proliferation of pulmonary artery smooth muscle cells (PASMCs) by regulating cell
      cycle proteins and whether the phosphodiesterase-5 (PDE5) inhibitor sildenafil
      affects calcineurin/NFAT-induced cell proliferation. MAIN METHODS: A
      [(3)H]thymidine incorporation assay was used to examine DNA synthesis (cell
      proliferation); cyclin A and NFATc2 expressions were determined by Western blot.
      Cyclin-dependent kinase 2 (CDK2) activity was measured with an in vitro kinase
      activity assay, and calcineurin and NFAT activity were evaluated using a
      calcineurin assay kit and a luciferase activity assay, respectively. A chemical
      inhibitor or siRNA transfection was used to inhibit calcineurin/NFAT signaling
      pathway. KEY FINDINGS: Serotonin dose-dependently stimulated cyclin A expression
      in PASMCs. This effect was accompanied by dose-dependent increases in CDK2
      activity and the rate of DNA synthesis. At the same time, PASMCs treated with
      serotonin showed dose-dependent activation of calcineurin/NFAT signaling pathway.
      Inhibition of calcineurin activity by cyclosporine A or loss of NFATc2 protein by
      siRNA transfection abolished serotonin-induced cyclin A expression and consequent
      CDK2 activation and DNA synthesis. We further found that pretreatment of cells
      with sildenafil suppressed serotonin-triggered activation of calcineurin/NFATc2
      signaling pathway and resultant cyclin A expression, CDK2 activation and cell
      proliferation, while the presence of DT-3 [a specific protein kinase G (PKG)
      peptide inhibitor] reversed the effects of sildenafil on PASMCs. SIGNIFICANCE:
      Our study suggests that enhanced PKG activity suppresses calcineurin/NFATc2
      cascade-mediated cyclin A expression, CDK2 activation and PASMC proliferation to
      contribute to the overall effects of sildenafil in the treatment of pulmonary
      hypertension.

PMID- 21851827
TI  - The antioxidant potential of alprazolam on the redox status of peripheral blood
      leukocytes in restraint-stressed mice.
AB  - AIMS: Stress can cause adverse reactions in the body that induce a wide range of
      biochemical and behavioral changes. Oxidative damage is an established outcome of
      stress that has been implicated in the pathogenesis of mood and anxiety
      disorders. Anxiolytic drugs are widely prescribed to treat these conditions;
      however, no animal study has investigated the effect of benzodiazepines on the
      levels of intracellular reactive oxygen species (ROS) in the peripheral blood
      leukocytes of stressed mice. MAIN METHODS: Mice were immobilized for a period of
      6h. Alprazolam (0.1-0.8 mg/kg of body weight) was administered 30 min before
      subjecting the animals to acute stress. The level of intracellular ROS in
      lymphocytes, granulocytes, and monocytes in the peripheral blood of stressed mice
      was investigated by using a 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe.
      KEY FINDINGS: Our results show that restraint stress significantly increases the
      generation of ROS in peripheral defense cells. Treatment with alprazolam
      partially reverses the adverse effects of stress. SIGNIFICANCE: Our findings
      suggest that the therapeutic efficacy of alprazolam may be mediated, at least
      partially, by the reversal of oxidative damage as demonstrated by the protective
      enhancement of antioxidant status following a stress-induced decline. Because
      alprazolam is used for the treatment of anxiety in patients with cancer,
      neurodegenerative disease, inflammatory bowel diseases, and other diseases, these
      results may have important clinical implications.

PMID- 21851829
TI  - Atherosclerosis induced by arsenic in drinking water in rats through altering
      lipid metabolism.
AB  - Arsenic in drinking water is a global environmental health problem, and the
      exposure may increase cardiovascular and cerebrovascular diseases mortalities,
      most likely through causing atherosclerosis. However, the mechanism of
      atherosclerosis formation after arsenic exposure is still unclear. To study the
      mechanism of atherosclerosis formation after arsenic exposure and explore the
      role of high cholesterol diet (HCD) in this process, we fed spontaneous
      hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with
      them drinking water containing arsenic at different ages and orders for 20
      consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat
      shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at
      predetermined intervals and determined expressions of cholesteryl ester transfer
      protein-1 (CETP-1) and liver X receptor beta (LXRbeta) in the liver.
      Atherosclerosis was determined by examining the aorta with hematoxylin and eosin
      stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote
      atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early
      combination exposure decreased the HDL-C/LDL-C ratio without changing the levels
      of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRbeta
      activities were suppressed, most significantly in early combination exposure. In
      conclusion, arsenic exposure may induce atherosclerosis through modifying reverse
      cholesterol transport in cholesterol metabolism and suppressing LXRbeta and CEPT
      1 expressions. For decreasing atherosclerosis related mortality associated with
      arsenic, preventing exposure from environmental sources in early life is an
      important element.

PMID- 21851828
TI  - Two decades of supertasting: where do we stand?
AB  - Oral chemosensation can vary greatly across individuals, both in terms of the
      lowest concentration that can be detected (threshold) and in the magnitude of
      perceived intensity for stimuli at higher concentrations (suprathreshold
      response). Individuals who experience greater taste intensity are often termed
      supertasters, and this phenotype has typically been measured via the
      suprathreshold bitterness of the tastant propylthiouracil (PROP). Notably,
      supertasting extends beyond bitterness and other tastants to include oral
      somatosensation and retronasal olfaction, and it may also include finer acuity as
      well. Here, we describe the evolution of the supertasting concept over the last
      20 years, and summarize the current state of the field. Alternative phenotyping
      approaches that are not dependent on PROP are reviewed, and the molecular
      genetics of broadly tuned heightened taste and orosensory response are discussed.
      We conclude by initiating a conversation on nomenclature as we look toward the
      next 20 years of chemosensory research.

PMID- 21851830
TI  - A case report of motor neuron disease in a patient showing significant level of
      DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane
      and toluene in blood.
AB  - Motor neuron disease is a devastating neurodegenerative condition, with the
      majority of sporadic, non-familial cases being of unknown etiology. Several
      epidemiological studies have suggested that occupational exposure to chemicals
      may be associated with disease pathogenesis. We report the case of a patient
      developing progressive motor neuron disease, who was chronically exposed to
      pesticides and organic solvents. The patient presented with leg spasticity and
      developed gradually clinical signs suggestive of amyotrophic lateral sclerosis,
      which was supported by the neurophysiologic and radiological findings. Our report
      is an evidence based case of combined exposure to organochlorine (DDTs),
      organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory
      analysis in samples of blood and hair confirming systematic exposure. The
      concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair
      (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and
      of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD+opDDT
      259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n
      hexane were also detected in blood on admission at hospital and quantified (1.23
      and 0.87 MUg/l, respectively), while 3 months after hospitalization blood testing
      was found negative for toluene and n-hexane and hair analysis was provided
      decrease levels of HCHs, DDTs and DAPs.

PMID- 21851832
TI  - A non-invasive approach to study lifetime exposure and bioaccumulation of PCBs in
      protected marine mammals: PBPK modeling in harbor porpoises.
AB  - In the last decade, physiologically based pharmacokinetic (PBPK) models have
      increasingly been developed to explain the kinetics of environmental pollutants
      in wildlife. For marine mammals specifically, these models provide a new, non
      destructive tool that enables the integration of biomonitoring activities and in
      vitro studies. The goals of the present study were firstly to develop PBPK models
      for several environmental relevant PCB congeners in harbor porpoises (Phocoena
      phocoena), a species that is sensitive to pollution because of its limited
      metabolic capacity for pollutant transformation. These models were tested using
      tissue data of porpoises from the Black Sea. Secondly, the predictive power of
      the models was investigated for time trends in the PCB concentrations in North
      Sea harbor porpoises between 1990 and 2008. Thirdly, attempts were made to assess
      metabolic capacities of harbor porpoises for the investigated PCBs. In general,
      results show that parameter values from other species (rodents, humans) are not
      always suitable in marine mammal models, most probably due to differences in
      physiology and exposure. The PCB 149 levels decrease the fastest in male harbor
      porpoises from the North Sea in a time period of 18years, whereas the PCB 101
      levels decrease the slowest. According to the models, metabolic breakdown of PCB
      118 is probably of lesser importance compared to other elimination pathways. For
      PCB 101 and 149 however, the presence of their metabolites can be attributed to
      bioaccumulation of metabolites from the prey and to metabolic breakdown of the
      parent compounds in the harbor porpoises.

PMID- 21851831
TI  - Non-additive hepatic gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) co-treatment in
      C57BL/6 mice.
AB  - Interactions between environmental contaminants can lead to non-additive effects
      that may affect the toxicity and risk assessment of a mixture. Comprehensive time
      course and dose-response studies with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      non-dioxin-like 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and their mixture were
      performed in immature, ovariectomized C57BL/6 mice. Mice were gavaged once with
      30 MUg/kg TCDD, 300 mg/kg PCB153, a mixture of 30 MUg/kg TCDD with 300 mg/kg
      PCB153 (MIX) or sesame oil vehicle for 4,12, 24,72 or 168 h. In the 24h dose
      response study, animals were gavaged with TCDD (0.3,1, 3, 6, 10, 15, 30, 45
      MUg/kg), PCB153 (3,10, 30, 60, 100, 150, 300, 450 mg/kg), MIX (0.3+3, 1+10, 3+30,
      6+60, 10+100, 15+150, 30+300, 45 MUg/kg TCDD+450 mg/kg PCB153, respectively) or
      vehicle. All three treatments significantly increased relative liver weights
      (RLW), with MIX eliciting significantly greater increases compared to TCDD and
      PCB153 alone. Histologically, MIX induced hepatocellular hypertrophy,
      vacuolization, inflammation, hyperplasia and necrosis, a combination of TCDD and
      PCB153 responses. Complementary lipid analyses identified significant increases
      in hepatic triglycerides in MIX and TCDD samples, while PCB153 had no effect on
      lipids. Hepatic PCB153 levels were also significantly increased with TCDD co
      treatment. Microarray analysis identified 167 TCDD, 185 PCB153 and 388 MIX unique
      differentially expressed genes. Statistical modeling of quantitative real-time
      PCR analysis of Pla2g12a, Serpinb6a, Nqo1, Srxn1, and Dysf verified non-additive
      expression following MIX treatment compared to TCDD and PCB153 alone. In summary,
      TCDD and PCB153 co-treatment elicited specific non-additive gene expression
      effects that are consistent with RLW increases, histopathology, and hepatic lipid
      accumulation.

PMID- 21851833
TI  - Neuroprotective effects of the 17beta-estradiol against ethanol-induced
      neurotoxicity and oxidative stress in the developing male rat cerebellum:
      biochemical, histological and behavioral changes.
AB  - During particular periods of central nervous system (CNS) development, exposure
      to ethanol can decrease regional brain growth and can result in selective loss of
      neurons. Unfortunately, there are few effective means of attenuating damage in
      the immature brain. In this study, the possible antioxidant and neuroprotective
      properties of 17beta-estradiol against ethanol-induced neurotoxicity was
      investigated. 17beta-estradiol (600 MUg/kg) was injected subcutaneously in
      postnatal day (PD) 4 and 5, 30 min prior to intraperitoneal injection of ethanol
      (6g/kg) in rat pups. Ninety minutes after injection of ethanol, the activities of
      several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT)
      and glutathione peroxidase (Gpx) in vermis of cerebellum were assayed.
      Thiobarbituric acid reactive substance (TBARS) levels were also measured as a
      marker of lipid peroxidation. Behavioral studies, including rotarod and locomotor
      activity tests were performed in PD 21-23 and histological study was performed
      after completion of behavioral measurements in postnatal day 23. The results of
      the present work demonstrated that ethanol could induce lipid peroxidation,
      increase TBARS levels and decrease glutathione peroxidase levels in pup
      cerebellum. We also observed that ethanol impaired performance on the rotarod and
      locomotor activities of rat pups. However, treatment with 17beta-estradiol
      significantly attenuated motoric impairment, the lipid peroxidation process and
      restored the levels of antioxidants. Histological analysis also indicated that
      ethanol could decrease vermis Purkinje cell count and 17beta-estradiol prevented
      this toxic effect. These results suggest that ethanol may induce lipid
      peroxidation in the rat pups cerebellum while treatment with 17beta-estradiol
      improves motor deficits by protecting the cerebellum against ethanol toxicity.

PMID- 21851835
TI  - Cholinergic control of male mating behavior in hamsters: effects of systemic
      agonist or antagonist treatment.
AB  - Sexual behavior in male rats is thought to depend in part on central cholinergic
      activity. In particular, previous studies of responses to systemically
      administered cholinergic drugs suggest that male rat behavior can be facilitated
      by the muscarinic agonist oxotremorine but is disrupted by the muscarinic
      antagonist scopolamine. However, it is not clear how broadly these effects
      generalize across species. To address this issue, we observed the impact on
      sexual behavior in male hamsters of systemic treatment with oxotremorine or
      scopolamine. In each case, the peripheral muscarinic antagonist methylscopolamine
      was used as an auxiliary or control treatment to better isolate central
      cholinergic effects. Both oxotremorine and scopolamine disrupted male behavior in
      hamsters. For example, both increased the likelihood of failure to achieve
      intromission or ejaculation. Further, even on completed tests oxotremorine
      treatment led to changes including increases in mount latency and postejaculatory
      interval while scopolamine treatment caused changes including increases in
      ejaculation latency and intromission frequency. The many changes caused by these
      treatments suggest that acetylcholine helps to control many elements of male
      behavior, probably by acting at multiple brain sites. The generally similar
      responses to a cholinergic agonist and antagonist suggest the dependence of
      efficient mating behavior on optimal levels of central cholinergic activity.

PMID- 21851834
TI  - Use of the light-dark box to compare the anxiety-related behavior of virgin and
      postpartum female rats.
AB  - Postpartum female rodents are less anxious than diestrous virgins and this
      difference contributes to dams' ability to adequately care for pups and defend
      the nest. Low postpartum anxiety has been observed in many behavioral paradigms
      but the results of previous studies using the light-dark box have been
      inconsistent. We here reexamined the usefulness of the light-dark box to assess
      differences between postpartum and diestrous virgin female rats in their anxiety
      related behavior. We found a significant effect of reproductive state, such that
      dams spent more time in the light chamber than did diestrous virgins. This
      difference required recent physical contact with pups because a four-hour
      separation from pups reduced dams' time spent in the light chamber by half,
      similar to what we previously found for litter-separated dams tested in an
      elevated plus maze. We then examined if dams' low-anxiety behavior in the light
      dark box depends on high GABA(A) receptor activity by inhibiting the receptor at
      different binding sites using (+)-Bicuculline to target the GABA site, FG-7142 to
      target the benzodiazepine site, and pentylenetetrazol to target the picrotoxin
      site. Only pentylenetetrazol was consistently anxiogenic in dams, while having
      little effect in diestrous virgins. Thus, the light-dark box can be a useful
      paradigm to study differences between postpartum and diestrous virgin female rats
      in their anxiety-related behaviors, and this difference is influenced by dams'
      recent contact with pups and GABA(A) receptor neurotransmission particularly
      affected by activity at the picrotoxin site.

PMID- 21851836
TI  - The effect of a smoke-free campus policy on college students' smoking behaviors
      and attitudes.
AB  - OBJECTIVE: To evaluate the impact of a smoke-free campus policy on college
      students' smoking behaviors and attitudes. METHODS: The current study utilized
      repeated cross-sectional surveys with a nested 4-wave longitudinal cohort design.
      Data were collected from undergraduate students at two large matched public
      universities in Indiana before and after one of the campuses went smoke-free in
      January 2008. Baseline data were collected in fall 2007 (n=3266) and follow-up
      data were collected in fall 2009 (n=3207). In addition, volunteers provided
      longitudinal follow-up data at four different time points. RESULTS: In the cross
      sectional analyses, students exposed to the smoke-free campus policy demonstrated
      significant favorable changes in smoking behavior (16.5% to 12.8%, p<0.001),
      perceptions of peer tobacco use (73.6% to 66.8%, p<0.001), and smoking norms
      (45.5% to 40.4%, p<0.001) compared to students on the control campus. In the
      longitudinal analyses, students exposed to the smoke-free campus policy
      demonstrated these changes plus significant favorable changes in attitudes toward
      regulation of tobacco (83.2% to 89.9%, p<0.01). CONCLUSIONS: The implementation
      of a smoke-free campus policy may be an effective intervention for reducing
      tobacco use among college students.

PMID- 21851837
TI  - Chlorimuron ethyl as a new selectable marker for disrupting genes in the insect
      pathogenic fungus Metarhizium robertsii.
AB  - A lack of selectable markers was a hindrance in investigating gene function in
      Metarhizium robertsii. A reliable Agrobacterium-mediated transformation system
      based on the use of chlorimuron ethyl as the selectable marker was developed
      which could serve as a useful tool to inactivate genes involved in insect
      pathogenicity.

PMID- 21851838
TI  - Fluorescence in situ hybridization for phytoplasma and endophytic bacteria
      localization in plant tissues.
AB  - In the present study, we developed a rapid and efficient fluorescence in situ
      hybridization assay (FISH) in non-embedded tissues of the model plant
      Catharanthus roseus for co-localizing phytoplasmas and endophytic bacteria,
      opening new perspectives for studying the interaction between these
      microorganisms.

PMID- 21851839
TI  - Differentiation among the Vibrio cholerae serotypes O1, O139, O141 and non-O1,
      non-O139, non-O141 using specific monoclonal antibodies with dot blotting.
AB  - Seven different monoclonal antibodies (MAbs) specific to only Vibrio cholerae
      were produced using a combination of five representative serotypes of V. cholerae
      for immunization. The first three MAbs (VC-93, VC-82 and VC-223) were specific to
      the V. cholerae serogroup O1 with different avidity for the serotypes O1 Inaba
      and O1 Ogawa. The fourth and the fifth MAbs were specific to V. cholerae O139 (VC
      812) or O141 (VC-191) serogroups, respectively. The sixth MAb (VC-26) bound to
      all three serogroups of V. cholerae. The seventh MAb (VC-63) bound to all twenty
      five isolates of V. cholerae used in this study. None of the seven MAbs showed
      cross-reactivity with other Vibrio spp. or closely-related V. cholerae species,
      V. mimicus or other gram-negative bacteria. The eighth MAbs (VC-201) specific to
      almost all Vibrio spp. was also obtained. In dot blotting, these MAbs can be used
      to detect a diluted pure culture of V. cholerae in solution with a sensitivity
      range of from 10(5) to 10(7) CFU ml(-1). However, the detection capability could
      be improved equivalent to that of PCR technique after preincubation of samples in
      alkaline peptone water (APW). Thus, these MAbs constitute convenient
      immunological tools that can be used for simple, rapid and simultaneous direct
      detection and differentiation of the individual serotypes of V. cholerae in
      complex samples, such as food and infected animals, without the requirement for
      bacterial isolation or biochemical characterization.

PMID- 21851840
TI  - Positive illusions and its association with cardiovascular functions.
AB  - The relationship between positive illusions (or self-enhancement) and
      cardiovascular functions was investigated using Asian samples in two studies. In
      phase 1 of Study 1, a generalized self-enhancement index was created for 241
      participants using a paired word association memory task, a facial emotion
      recognition task, and a reading test. 122 participants subsequently volunteered
      for a second phase in this study where their ambulatory cardiovascular functions
      were measured throughout a single waking day. In Study 2, a priming procedure
      experimentally induced self-enhancement (n=35) and self-effacement (n=37) and the
      participants' cardiovascular arousal and perceived control for a mental
      arithmetic task were measured. Self-enhancement predicted lower cardiovascular
      functions for both studies. In Study 1, self-enhancement assessed at phase 2 was
      a significant predictor while self-enhancement measured at phase 1 was not. In
      Study 2, the relationship between self-enhancement and vascular reactivity was
      partially mediated by perceived control. The findings indicate that the
      relationship between self-enhancement and cardiovascular stress response, which
      has implications for cardiovascular health, (i) is relevant for Asian
      populations, (ii) is not just correlational but potentially causal, and (iii) is
      partly mediated by an increase in perceived control for vascular reactivity.

PMID- 21851841
TI  - Combined effect of depressive symptoms and hostility on autonomic nervous system
      function.
AB  - Depression and hostility have been separately related to indicators of
      sympathetic hyperactivation and parasympathetic hypoactivation. We examined the
      associations of depressive symptoms, hostility, and their interaction with pre
      ejection period (PEP) and high frequency heart rate variability (HRV), specific
      indices of sympathetic and parasympathetic cardiac control, respectively.
      Healthy, young adults (N=120) completed questionnaires assessing depressive
      symptoms and hostility and underwent autonomic testing. Although main effects
      were not observed, a depressive symptoms*hostility interaction was detected for
      PEP (beta=.25, p=.01). Simple slope analyses revealed that hostility was
      negatively related to PEP among individuals with low depressive symptoms but was
      not associated with PEP among those with mild-to-moderate depressive symptoms. No
      interaction effect was detected for high frequency HRV. Our findings suggest that
      depressive symptoms may moderate the link between hostility and sympathetic
      activation such that hostility is accompanied by sympathetic hyperactivation only
      when depressive symptoms are minimal.

PMID- 21851842
TI  - To go or not to go, that is the question: do the N2 and P3 reflect stimulus- or
      response-related conflict?
AB  - Several studies have linked increases in the N2 and P3 components to response
      conflict, evoked when multiple incompatible responses are simultaneously
      activated. However, these studies confound a change of response with a change of
      stimulus identity, and often a change in stimulus probability also. In two
      experiments, additional trial types were presented, which signified a change of
      stimulus, but still demanded the expected response. RT costs were observed when
      participants changed a planned response to a different one, and when they
      activated an unplanned response, but RT was not substantially increased for
      stimulus mismatch trials when these were clearly linked to the required response.
      N2 results were mixed and did not clearly favour a stimulus mismatch or response
      conflict interpretation. For the P3 component, stimulus-related differences were
      small but significant, with large increases in positivity when participants
      cancelled the planned response. Further experiments are required to determine the
      relative contribution of stimulus- and response-related conflict to N2.

PMID- 21851843
TI  - Stearoyl gemcitabine nanoparticles overcome resistance related to the over
      expression of ribonucleotide reductase subunit M1.
AB  - Gemcitabine is a deoxycytidine analog used in the treatment of various solid
      tumors. However, tumors often develop resistances over time, which becomes a
      major issue for most gemcitabine-related chemotherapies. In the present study, a
      previously reported stearoyl gemcitabine nanoparticle formulation (GemC18-NPs)
      was evaluated for its ability to overcome gemcitabine resistance. In the wild
      type CCRF-CEM human leukemia cells, the IC(50) value of GemC18-NPs was 9.5-fold
      greater than that of gemcitabine hydrochloride (HCl). However, in the CCRF-CEM
      AraC-8C cells that are deficient in the human equilibrative nucleoside
      transporter-1, the IC(50) of GemC18-NPs was only 3.4-fold greater than that in
      the parent CCRF-CEM cells, whereas the IC(50) of gemcitabine HCl was 471-fold
      greater than that in the parent CCRF-CEM cells. The GemC18-NPs were also more
      cytotoxic than gemcitabine HCl in the deoxycytidine kinase deficient (CCRF
      CEM/dCK(-/-)) tumor cells. Similar to gemcitabine HCl, GemC18-NPs induced
      apoptosis through caspase activation. Another gemcitabine-resistant tumor cell
      line, TC-1-GR, was developed in our laboratory. In the TC-1-GR cells, the IC(50)
      of GemC18-NPs was only 5% of that of gemcitabine HCl. Importantly, GemC18-NPs
      effectively controlled the growth of gemcitabine resistant TC-1-GR tumors in
      mice, whereas the molar equivalent dose of gemcitabine HCl did not show any
      activity against the growth of the TC-1-GR tumors. Proteomics analysis revealed
      that the TC-1-GR cells over-expressed ribonucleotide reductase M1, which was
      likely the cause of the acquired gemcitabine resistance in the TC-1-GR cells. To
      our best knowledge, this represents the first report demonstrating that a
      nanoparticle formulation of gemcitabine overcomes gemcitabine resistance related
      to ribonucleotide reductase M1 over-expression.

PMID- 21851845
TI  - Programmed death-1 (PD-1)/PD-1 ligand pathway-mediated immune responses against
      human T-lymphotropic virus type 1 (HTLV-1) in HTLV-1-associated
      myelopathy/tropical spastic paraparesis and carriers with autoimmune disorders.
AB  - Human T-lymphotropic virus-1 (HTLV-1) causes HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia
      lymphoma in individuals with dysfunctional immune responses. In this study, to
      characterize the HTLV-1-specific cytotoxic T lymphocyte (CTL) populations in
      asymptomatic HTLV-1 carriers (ACs), HAM/TSP patients, and carriers with
      autoimmune disorders (CAIDs), we examined the role of programmed death-1 and its
      ligand (PD-1/PD-L1) in HTLV-1-specific CTL functions using an HTLV-1 Tax/HLA
      A*0201 tetramer and an HTLV-1 Tax/HLA-A*2402 tetramer. Interestingly, the
      percentage of HTLV-1 Tax301-309/HLA-A*2402 tetramer(+)CD8(+) cells expressing PD
      1 in ACs was significantly higher than the percentage of HTLV-1 Tax11-19/HLA
      A*0201 tetramer(+)CD8(+) cells expressing PD-1. PD-1 expression was significantly
      downregulated on HTLV-1-specific CTLs in HAM/TSP compared with ACs. PD-L1
      expression was observed in a small proportion of unstimulated lymphocytes from
      ACs and was greater in ACs than in HAM/TSP and CAIDs after short-term culture.
      Furthermore, CTL degranulation was impaired in HAM/TSP, whereas anti-PD-L1
      blockade significantly increased CTL function in ACs. Downregulation of PD-1 on
      HTLV-1-specific CTLs and loss of PD-L1 expression in HAM/TSP and CAIDs, along
      with impaired function of HTLV-1-specific CTLs in HAM/TSP, may underlie the
      apparently dysfunctional immune response against HTLV-1.

PMID- 21851844
TI  - Hybrid magnetic nanostructures (MNS) for magnetic resonance imaging applications.
AB  - The development of MRI contrast agents has experienced its version of the gilded
      age over the past decade, thanks largely to the rapid advances in nanotechnology.
      In addition to progress in single mode contrast agents, which ushered in
      unprecedented R(1) or R(2) sensitivities, there has also been a boon in the
      development of agents covering more than one mode of detection. These include
      T(1)-PET, T(2)-PET T(1)-optical, T(2)-optical, T(1)-T(2) agents and many others.
      In this review, we describe four areas which we feel have experienced particular
      growth due to nanotechnology, specifically T(2) magnetic nanostructure
      development, T(1)/T(2)-optical dual mode agents, and most recently the T(1)-T(2)
      hybrid imaging systems. In each of these systems, we describe applications
      including in vitro, in vivo usage and assay development. In all, while the
      benefits and drawbacks of most MRI contrast agents depend on the application at
      hand, the recent development in multimodal nanohybrids may curtail the
      shortcomings of single mode agents in diagnostic and clinical settings by
      synergistically incorporating functionality. It is hoped that as nanotechnology
      advances over the next decade, it will produce agents with increased diagnostics
      and assay relevant capabilities in streamlined packages that can meaningfully
      improve patient care and prognostics. In this review article, we focus on T(2)
      materials, its surface functionalization and coupling with optical and/or T(1)
      agents.

PMID- 21851847
TI  - Association between brain-derived neurotrophic factor Val66Met and obesity in
      children and adolescents.
AB  - Obesity in children and adolescents is a worldwide health problem, characterized
      by various somatic, psychosocial and psychiatric complications, and is often
      associated with adult obesity and related complications. Brain-derived
      neurotrophic factor (BDNF) is a neurotrophin with important roles in feeding
      behavior, food intake regulation, energy metabolism and weight control. A common
      polymorphism of the BDNF genotype (Val66Met) has been associated with various
      forms of eating disorders, alterations in body mass index (BMI) values and
      obesity in adult populations. The aim of this study was to determine the
      association between the gene variants of the BDNF Val66Met polymorphism and
      obesity in 300 healthy Caucasian children and adolescents of the same ethnic
      background of Croatian origin, subdivided according to the BMI percentile, but
      without any form of eating disorders. The frequency of the Met/Met, Met/Val and
      Val/Val genotypes, Met and Val alleles, and Met carriers (the combined Met/Met
      and Met/Val genotypes versus the homozygous Val/Val genotype) differed
      significantly between underweight, normal weight, overweight and obese children,
      and the presence of one or two Met alleles contributed to this significant
      effect. These results showed for the first time the significant association
      between the presence of one or two Met alleles and obesity in ethnically
      homogenous groups of healthy Caucasian children and adolescents. These data
      confirmed the major role of BDNF in energy metabolism, food regulation and BMI.

PMID- 21851846
TI  - Validation of candidate genes associated with cardiovascular risk factors in
      psychiatric patients.
AB  - The purpose of this study was to identify genetic variants predictive of
      cardiovascular risk factors in a psychiatric population treated with second
      generation antipsychotics (SGA). 924 patients undergoing treatment for severe
      mental illness at four US hospitals were genotyped at 1.2 million single
      nucleotide polymorphisms. Patients were assessed for fasting serum lipid (low
      density lipoprotein cholesterol [LDLc], high density lipoprotein cholesterol
      [HDLc], and triglycerides) and obesity phenotypes (body mass index, BMI).
      Thirteen candidate genes from previous studies of the same phenotypes in non
      psychiatric populations were tested for association. We confirmed 8 of the 13
      candidate genes at the 95% confidence level. An increased genetic effect size was
      observed for triglycerides in the psychiatric population compared to that in the
      cardiovascular population.

PMID- 21851848
TI  - Induction of expression and functional activity of P-glycoprotein efflux
      transporter by bioactive plant natural products.
AB  - The effect of bioactive plant natural products on the expression and functional
      activity of P-glycoprotein (P-gp) is poorly understood. Interactions of bioactive
      plant-based food and dietary supplements with P-gp can cause significant
      alteration of pharmacokinetic properties of P-gp substrate drugs when used in
      combination. This can augment toxicity and/or interfere with the drug's
      therapeutic outcomes. This study investigated the effects of diverse commonly
      used plant natural products on the expression and activity of P-gp in human
      adenocarcinoma cells (LS-180). These natural products included the tobacco
      cembranoid (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (cembratriene), the
      palm oil-derived gamma-tocotrienol, the extra-virgin olive oil-derived
      secoiridoid oleocanthal, and the triterpene acid asiatic acid derived from
      Melaleuca ericifolia and abundant in several other common plant dietary
      supplements. Treatment with 25MUM of cembratriene, oleocanthal, gamma
      tocotrienol, or asiatic acid showed 2.3-3.0-fold increase in P-gp expression as
      demonstrated by Western blotting. These results were consistent with those
      obtained by quantitative analysis of fluorescent micrographs for P-gp.
      Accumulation studies demonstrated 31-38% decrease in rhodamine 123 intracellular
      levels when LS-180 cells were treated with the investigated compounds as a result
      of P-gp induction. Bioactive natural products can up-regulate the P-gp expression
      and functionality, which may induce herb/food-drug interactions when
      concomitantly used with P-gp substrate drugs.

PMID- 21851849
TI  - Fragrance material review on 3-phenylpropyl isobutyrate.
AB  - A toxicologic and dermatologic review of 3-phenylpropyl isobutyrate when used as
      a fragrance ingredient is presented. 3-Phenylpropyl isobutyrate is a member of
      the fragrance structural group cinnamyl phenylpropyl compounds. The common
      characteristic structural element of cinnamyl phenylpropyl materials is an aryl
      substituted primary alcohol/aldehyde/ester. They are simple aromatic compounds
      with saturated propyl or unsaturated propenyl side chains containing a primary
      oxygenated functional group which has little toxic potential. 3-Phenyl-1-propyl
      derivatives participate in the same beta oxidation pathways as do their parent
      cinnamic acid derivatives. This review contains a detailed summary of all
      available toxicology and dermatology papers that are related to this individual
      fragrance ingredient and is not intended as a stand-alone document. Available
      data for 3-phenylpropyl isobutyrate was evaluated then summarized and includes
      physical properties, acute toxicity, skin irritation and skin sensitization. A
      safety assessment of all cinnamyl phenyl propyl compounds will be published
      simultaneously with this document. Please refer to Belsito et al. (2011) for an
      overall assessment of the safe use of this material and all cinnamyl phenylpropyl
      materials in fragrances. Belsito, D., Bickers, D., Bruze, M., Dagli, M.L., Fryer,
      A., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and
      dermatologic assessment of cinnamyl phenylpropyl compounds when used as fragrance
      ingredients.

PMID- 21851851
TI  - Expression patterns of mineralocorticoid and glucocorticoid receptors in
      Bengalese finch (Lonchura striata var. domestica) brain suggest a relationship
      between stress hormones and song-system development.
AB  - Much evidence suggests that song traits function as an honest signal of male
      quality during mate choice in songbirds. Because songbirds learn vocalizations
      during the juvenile stage, development of the song system and song traits is
      affected by stressful conditions. However, it remains unknown how stressful
      conditions affect later song traits during development. To explore the
      relationship between glucocorticoids and song-system development, we performed in
      situ hybridization analysis of the glucocorticoid and mineralocorticoid receptors
      in juvenile and adult brains. The glucocorticoid receptor showed weak expression
      in song nuclei and strong expression in the hypothalamus, whereas the
      mineralocorticoid receptor showed strong song-nuclei-related expression. Thus, it
      appears that glucocorticoids are involved in song development directly by binding
      to receptors in song nuclei or indirectly by regulating sex hormones through
      hypothalamic hormones.

PMID- 21851852
TI  - The cDNA sequence of three hemocyanin subunits from the garden snail Helix
      lucorum.
AB  - Hemocyanins are blue copper containing respiratory proteins residing in the
      hemolymph of many molluscs and arthropods. They can have different molecular
      masses and quaternary structures. Moreover, several molluscan hemocyanins are
      isolated with one, two or three isoforms occurring as decameric, didecameric,
      multidecameric or tubule aggregates. We could recently isolate three different
      hemocyanin isopolypeptides from the hemolymph of the garden snail Helix lucorum
      (HlH). These three structural subunits were named alpha(D)-HlH, alpha(N)-HlH and
      beta-HlH. We have cloned and sequenced their cDNA which is the first result ever
      reported for three isoforms of a molluscan hemocyanin. Whereas the complete gene
      sequence of alpha(D)-HlH and beta-HlH was obtained, including the 5' and 3' UTR,
      180bp of the 5' end and around 900bp at the 3' end are missing for the third
      subunit. The subunits alpha(D)-HlH and beta-HlH comprise a signal sequence of 19
      amino acids plus a polypeptide of 3409 and 3414 amino acids, respectively. We
      could determine 3031 residues of the alpha(N)-HLH subunit. Sequence comparison
      with other molluscan hemocyanins shows that alpha(D)-HlH is more related to
      Aplysia californicum hemocyanin than to each of its own isopolypeptides. The
      structural subunits comprise 8 different functional units (FUs: a, b, c, d, e, f,
      g, h) and each functional unit possesses a highly conserved copper-A and copper-B
      site for reversible oxygen binding. Potential N-glycosylation sites are present
      in all three structural subunits. We confirmed that all three different isoforms
      are effectively produced and secreted in the hemolymph of H. lucorum by analyzing
      a tryptic digest of the purified native hemocyanin by MALDI-TOF and LC-FTICR mass
      spectrometry.

PMID- 21851853
TI  - A new method of calculating auditory excitation patterns and loudness for steady
      sounds.
AB  - A new method for calculating auditory excitation patterns and loudness for steady
      sounds is described. The method is based on a nonlinear filterbank in which each
      filter is the sum of a broad passive filter and a sharp active filter. All
      filters have a rounded-exponential shape. For each center frequency (CF), the
      gain of the active filter is controlled by the output of the passive filter. The
      parameters of the model were derived from large sets of previously published
      notched-noise masking data obtained from human subjects. Excitation patterns
      derived using the new filterbank include the effects of basilar membrane
      compression. Loudness can be calculated as the area under the excitation pattern
      when plotted in intensity-like units on an ERB(N)-number (Cam) scale; no
      transformation from excitation to specific loudness is required. The method
      predicts the standard equal-loudness contours and loudness as a function of
      bandwidth with good accuracy. With some additional assumptions, the method also
      gives reasonably accurate predictions of partial loudness.

PMID- 21851854
TI  - Regulation of hSos1 activity is a system-level property generated by its multi
      domain structure.
AB  - The multi-domain protein hSos1 plays a major role in cell growth and
      differentiation through its Ras-specific guanine nucleotide exchange domain whose
      complex regulation involves intra-molecular, inter-domain rearrangements. We
      present a stochastic mathematical model describing intra-molecular regulation of
      hSos1 activity. The population macroscopic effect is reproduced through a Monte
      Carlo approach. Key model parameters have been experimentally determined by
      BIAcore analysis. Complementation experiments of a Saccharomyces cerevisiae
      cdc25(ts) strain with Sos deletion mutants provided a comprehensive data set for
      estimation of unknown parameters and model validation. The model is robust
      against parameter alteration and describes both the behavior of Sos deletion
      mutants and modulation of activity of the full length molecule under
      physiological conditions. By incorporating the calculated effect of amino acid
      changes at an inter-domain interface, the behavior of a mutant correlating with a
      developmental syndrome could be simulated, further validating the model. The
      activation state of Ras-specific guanine nucleotide exchange domain of hSos1
      arises as an "emergent property" of its multi-domain structure that allows multi
      level integration of a complex network of intra- and inter-molecular signals.

PMID- 21851855
TI  - Whole-genome comparison clarifies close phylogenetic relationships between the
      phyla Dictyoglomi and Thermotogae.
AB  - The anaerobic thermophilic bacterial genus Dictyoglomus is characterized by the
      ability to produce useful enzymes such as amylase, mannanase, and xylanase.
      Despite the significance, the phylogenetic position of Dictyoglomus has not yet
      been clarified, since it exhibits ambiguous phylogenetic positions in a single
      gene sequence comparison-based analysis. The number of substitutions at the
      diverging point of Dictyoglomus is insufficient to show the relationships in a
      single gene comparison-based analysis. Hence, we studied its evolutionary trait
      based on whole-genome comparison. Both gene content and orthologous protein
      sequence comparisons indicated that Dictyoglomus is most closely related to the
      phylum Thermotogae and it forms a monophyletic group with Coprothermobacter
      proteolyticus (a constituent of the phylum Firmicutes) and Thermotogae. Our
      findings indicate that C. proteolyticus does not belong to the phylum Firmicutes
      and that the phylum Dictyoglomi is not closely related to either the phylum
      Firmicutes or Synergistetes but to the phylum Thermotogae.

PMID- 21851850
TI  - The transferrin receptor and the targeted delivery of therapeutic agents against
      cancer.
AB  - BACKGROUND: Traditional cancer therapy can be successful in destroying tumors,
      but can also cause dangerous side effects. Therefore, many targeted therapies are
      in development. The transferrin receptor (TfR) functions in cellular iron uptake
      through its interaction with transferrin. This receptor is an attractive molecule
      for the targeted therapy of cancer since it is upregulated on the surface of many
      cancer types and is efficiently internalized. This receptor can be targeted in
      two ways: 1) for the delivery of therapeutic molecules into malignant cells or 2)
      to block the natural function of the receptor leading directly to cancer cell
      death. SCOPE OF REVIEW: In the present article we discuss the strategies used to
      target the TfR for the delivery of therapeutic agents into cancer cells. We
      provide a summary of the vast types of anti-cancer drugs that have been delivered
      into cancer cells employing a variety of receptor binding molecules including Tf,
      anti-TfR antibodies, or TfR-binding peptides alone or in combination with carrier
      molecules including nanoparticles and viruses. MAJOR CONCLUSIONS: Targeting the
      TfR has been shown to be effective in delivering many different therapeutic
      agents and causing cytotoxic effects in cancer cells in vitro and in vivo.
      GENERAL SIGNIFICANCE: The extensive use of TfR for targeted therapy attests to
      the versatility of targeting this receptor for therapeutic purposes against
      malignant cells. More advances in this area are expected to further improve the
      therapeutic potential of targeting the TfR for cancer therapy leading to an
      increase in the number of clinical trials of molecules targeting this receptor.
      This article is part of a Special Issue entitled Transferrins: molecular
      mechanisms of iron transport and disorders.

PMID- 21851856
TI  - The effects of APOE on the functional architecture of the resting brain.
AB  - There is a well-established association between APOE genotype and the risk of
      developing Alzheimer's disease (AD). Relative to individuals with the common
      epsilon3/epsilon3 genotype, carriers of the epsilon4 allele are at increased risk
      of developing AD, while carriers of the epsilon2 allele appear to be protected
      against the disease. However, we recently reported that in a sample of
      cognitively healthy adults, both epsilon4 and epsilon2 carriers showed nearly
      identical changes in the pattern of fMRI activity during memory and non-memory
      tasks, relative to epsilon3 homozygotes. These findings suggest that the effects
      of APOE on brain function are not tightly linked to the effects of this gene on
      AD risk. Here we test the hypothesis that APOE has an intrinsic effect on the
      brain's functional networks. Resting-state fMRI was used to compare the pattern
      of functional connectivity of a variety of resting-state networks between 77
      cognitively healthy participants aged 32 to 55 with different APOE genotypes (23
      epsilon2/epsilon3, 20 epsilon3/epsilon3, 26 epsilon3/epsilon4, and 8
      epsilon4/epsilon4). Differences between genotype groups were found in two
      hippocampal networks, the auditory network, the left frontal-parietal network,
      and the lateral visual network. While there was considerable variety in the brain
      regions affected and the direction of change across networks, the main finding
      was that changes in functional connectivity were similar in epsilon4 and epsilon2
      carriers, relative to epsilon3 homozygotes. APOE appears to have an intrinsic
      effect on the differentiation of functional networks in the brain. This effect is
      apparent in cognitively healthy adults and does not manifest in a manner
      reflective of the link between APOE and AD risk. Rather, the effects of APOE on
      brain function may relate to the role of this gene in neurodevelopment.

PMID- 21851858
TI  - Evolutionary history of the Corallinales (Corallinophycidae, Rhodophyta) inferred
      from nuclear, plastidial and mitochondrial genomes.
AB  - Systematics of the red algal order Corallinales has a long and convoluted
      history. In the present study, molecular approaches were used to assess the
      phylogenetic relationships based on the analyses of two datasets: a large dataset
      of SSU sequences including mainly sequences from GenBank; and a combined dataset
      including four molecular markers (two nuclear: SSU, LSU; one plastidial: psbA;
      and one mitochondrial: COI). Phylogenetic analyses of both datasets re-affirmed
      the monophyly of the Corallinales as well as the two families (Corallinaceae and
      Hapalidiaceae) currently recognized within the order. Three of the four
      subfamilies of the Corallinaceae (Corallinoideae, Lithophylloideae,
      Metagoniolithoideae) were also resolved as a monophyletic lineage whereas members
      of the Mastophoroideae were resolved as four distinct lineages. We therefore
      propose to restrict the Mastophoroideae to the genera Mastophora, Metamastophora,
      and possibly Lithoporella in the aim of rendering this subfamily monophyletic. In
      addition, our phylogenies resolved the genus Hydrolithon in two unrelated
      lineages, one containing the generitype Hydrolithon reinboldii and the second
      containing Hydrolithon onkodes, which used to be the generitype of the now
      defunct genus Porolithon. We therefore propose to resurrect the genus Porolithon
      for the second lineage encompassing those species with primarily monomerous
      thalli, and trichocyte arrangements in large pustulate horizontal rows. Moreover,
      our phylogenetic analyses revealed the presence of cryptic diversity in several
      taxa, shedding light on the need for further studies to better circumscribe
      species frontiers within the diverse order Corallinales, especially in the genera
      Mesophyllum and Neogoniolithon.

PMID- 21851857
TI  - Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in
      layers IV-V of the rat whisker-barrel cortex.
AB  - The spatiotemporal characteristics of the hemodynamic response to increased
      neural activity were investigated at the level of individual intracortical
      vessels using BOLD-fMRI in a well-established rodent model of somatosensory
      stimulation at 11.7 T. Functional maps of the rat barrel cortex were obtained at
      150 * 150 * 500 MUm spatial resolution every 200 ms. The high spatial resolution
      allowed separation of active voxels into those containing intracortical macro
      vessels, mainly vein/venules (referred to as macrovasculature), and those
      enriched with arteries/capillaries and small venules (referred to as
      microvasculature) since the macro vessel can be readily mapped due to the fast T2
      decay of blood at 11.7 T. The earliest BOLD response was observed within layers
      IV-V by 0.8s following stimulation and encompassed mainly the voxels containing
      the microvasculature and some confined macrovasculature voxels. By 1.2s, the BOLD
      signal propagated to the macrovasculature voxels where the peak BOLD signal was 2
      3 times higher than that of the microvasculature voxels. The BOLD response
      propagated in individual venules/veins far from neuronal sources at later times.
      This was also observed in layers IV-V of the barrel cortex after specific
      stimulation of separated whisker rows. These results directly visualized that the
      earliest hemodynamic changes to increased neural activity occur mainly in the
      microvasculature and spread toward the macrovasculature. However, at peak
      response, the BOLD signal is dominated by penetrating venules even at layers IV-V
      of the cortex.

PMID- 21851859
TI  - Differences in oxygen consumption and diel activity as adaptations related to
      microhabitat in Neotropical freshwater decapods (Crustacea).
AB  - This study evaluated oxygen consumption (MO(2)) and diel activity in Aegla
      longirostri, Trichodactylus panoplus and Parastacus brasiliensis (three species
      of freshwater decapods that occur in sympatry), under two different conditions of
      O(2) availability, limited and constant; and searched for the existence of a
      relationship between these two variables. The Kruskal-Wallis test showed that in
      all the species, MO(2) was higher under constant O(2) availability; T. panoplus
      and P. brasiliensis showed an oxygen-dependent pattern, while A. longirostri
      showed higher MO(2) values and less variation in the values between the
      treatments, indicating a higher and more oxygen-independent metabolism. P.
      brasiliensis was more active in constant O(2). A. longirostri was more active in
      limited O(2) and did not show a clear diel activity in any case, showing
      behavioral changes when in unfavorable conditions. The Spearman's rank
      correlation analysis did not indicate any relationship between MO(2) and
      activity. These results indicate a higher metabolism in A. longirostri. The less
      demanding metabolisms of P. brasiliensis and T. panoplus allow these species to
      occupy environments that are unavailable to A. longirostri due to differences in
      dissolved-oxygen concentrations.

PMID- 21851860
TI  - Forecasting elasmobranch survival following exposure to severe stressors.
AB  - Current fishing practices and habitat degradation in most of the world's oceans
      pose significant threats to marine fish including elasmobranchs. The accurate
      prediction of survival probability for elasmobranchs subjected to prolonged
      immobilisation and diminished oxygen availability during capture and a vulnerable
      state post-release, is reliant on selecting a reliable set of biomarkers to
      profile as well as using them to design pre-release interventions which minimise
      elasmobranch death. The purpose of this review is: i) to make a case for the need
      to develop new biomarkers to use in conjunction with blood chemistry; ii) to
      briefly present the survival strategies used by other vertebrates subjected to
      diminished oxygen iii) to discuss new approaches to forecasting the effect that
      altered physiological and biochemical markers have on long-term survival with a
      particular emphasis on oxidative stress, the adenylate energy charge, heat shock
      protein expression and the capacity for repair, so that a more detailed profile
      of the qualities of elasmobranch survivorship can be constructed. In addition,
      the review will discuss the relevance of biomarkers to field samples as well as
      their incorporation into laboratory based research, aimed at providing
      physiological and biochemical data to inform conservation management.

PMID- 21851861
TI  - Liquid chromatographic-mass spectrometric analysis of phospholipids.
      Chromatography, ionization and quantification.
AB  - This review deals with the LC-MS analysis of phospholipids. The advantages of
      including liquid chromatography in phospholipids are highlighted. Special
      attention is paid to the most-used ionization methods and the role of solvents in
      chromatography and ionization. Difficulties associated with different
      quantification strategies are discussed.

PMID- 21851862
TI  - Generation of free radicals in haemocytes of mussels after exposure to low
      molecular weight PAH components: immune activation, oxidative and genotoxic
      effects.
AB  - Polycyclic aromatic hydrocarbons (PAHs) constituents, such as phenanthrene (PH)
      and anthracene (AN), are considered toxic for marine organisms, including bivalve
      mollusks. The present study showed that the perturbation of health status in
      mussels, as well as their inability to survive in air (stress on stress
      response), following exposure to either PH or AN (at a final concentration of 0.1
      mg/L respectively), and a mixture of them (ration 1:1, at a final concentration
      of 0.2 mg/L) for 7 days, is probably related with alterations occurred in their
      haemocytes. According to the present study, PH and AN, either alone or in a
      mixture, could induce elevated levels of superoxide anions ((*)O(2)(-)) within
      haemocytes of mussels, thus leading to immune susceptibility as indicated by the
      increased levels of cell death and the elevated levels of lysosomal membrane acid
      phosphatase (AcP) activity, probably occurred via its overproduction or its
      release into the cytosol after lysosomal membrane destabilisation. PAH-mediated
      oxidative and genotoxic effects, indicated by the increased levels of both lipid
      peroxidation (MDA content) and nuclear abnormalities (MN test) could be related
      with haemocytes' inability to overcome free radical generation, thus leading to
      attenuation of general health status, before other disturbances, such as death,
      occur.

PMID- 21851865
TI  - Redox proteomics.

PMID- 21851864
TI  - An insight into the sialotranscriptome and proteome of the coarse bontlegged
      tick, Hyalomma marginatum rufipes.
AB  - Ticks are mites specialized in acquiring blood from vertebrates as their sole
      source of food and are important disease vectors to humans and animals. Among the
      specializations required for this peculiar diet, ticks evolved a sophisticated
      salivary potion that can disarm their host's hemostasis, inflammation, and immune
      reactions. Previous transcriptome analysis of tick salivary proteins has revealed
      many new protein families indicative of fast evolution, possibly due to host
      immune pressure. The hard ticks (family Ixodidae) are further divided into two
      basal groups, of which the Metastriata have 11 genera. While salivary
      transcriptomes and proteomes have been described for some of these genera, no
      tick of the genus Hyalomma has been studied so far. The analysis of 2084
      expressed sequence tags (EST) from a salivary gland cDNA library allowed an
      exploration of the proteome of this tick species by matching peptide ions derived
      from MS/MS experiments to this data set. We additionally compared these MS/MS
      derived peptide sequences against the proteins from the bovine host, finding many
      host proteins in the salivary glands of this tick. This annotated data set can
      assist the discovery of new targets for anti-tick vaccines as well as help to
      identify pharmacologically active proteins.

PMID- 21851866
TI  - Low abundance protein enrichment for discovery of candidate plasma protein
      biomarkers for early detection of breast cancer.
AB  - Molecular biomarkers of early stage breast cancer may improve the sensitivity and
      specificity of diagnosis. Plasma biomarkers have additional value in that they
      can be monitored with minimal invasiveness. Plasma biomarker discovery by genome
      wide proteomic methods is impeded by the wide dynamic range of protein abundance
      and the heterogeneity of protein expression in healthy and disease populations
      which requires the analysis of a large number of samples. We addressed these
      issues through the development of a novel protocol that couples a combinatorial
      peptide ligand library protein enrichment strategy with isobaric label-based 2D
      LC-MS/MS for the identification of candidate biomarkers in high throughput.
      Plasma was collected from patients with stage I breast cancer or benign breast
      lesions. Low abundance proteins were enriched using a bead-based combinatorial
      library of hexapeptides. This resulted in the identification of 397 proteins, 22%
      of which are novel plasma proteins. Twenty-three differentially expressed plasma
      proteins were identified, demonstrating the effectiveness of the described
      protocol and defining a set of candidate biomarkers to be validated in
      independent samples. This work can be used as the basis for the design of
      properly powered investigations of plasma protein expression for biomarker
      discovery in larger cohorts of patients with complex disease.

PMID- 21851867
TI  - Erythropoietin stimulates bone formation, cell proliferation, and angiogenesis in
      a femoral segmental defect model in mice.
AB  - The glycoprotein erythropoietin (EPO) has been demonstrated to stimulate fracture
      healing. The aim of the present study was to investigate the effect of EPO
      treatment on bone repair in a femoral segmental defect model. Bone repair was
      analyzed in mice which were treated by EPO (500IE/kg/d intraperitoneally; n=38)
      and in mice which received the vehicle for control (n=40). Two and 10 weeks after
      creating a 1.8mm femoral segmental defect, bone repair was studied by micro-CT,
      histology, and Western blot analysis. At 10 weeks, micro-CT and histomorphometric
      analyses showed a significantly higher bridging rate of the bone defects in EPO
      treated animals than in controls. This was associated by a significantly higher
      bone volume within the segmental defects of the EPO-treated animals. At 2 weeks,
      Western blot analyses revealed a significantly higher expression of vascular
      endothelial growth factor (VEGF) in EPO-treated animals compared to controls.
      Accordingly, the number of blood vessels was significantly increased in the EPO
      group at 2 weeks. At 10 weeks, we found a significantly higher expression of
      proliferating cell nuclear antigen (PCNA) in EPO-treated animals when compared to
      controls. Western blot analyses showed no significant differences between the
      groups in the expression of the endothelial and inducible nitric oxide synthases
      (eNOS and iNOS) and the angiopoietin receptor Tie-2. Immunohistochemistry
      confirmed the results of the Western blot analyses, demonstrating a significantly
      higher number of VEGF- and PCNA-positive cells in EPO-treated animals than in
      controls at 2 and 10 weeks, respectively. We conclude that EPO is capable of
      stimulating bone formation, cell proliferation and VEGF-mediated angiogenesis in
      a femoral segmental defect model.

PMID- 21851868
TI  - Sex differences in trabecular bone microarchitecture are not detected in pre and
      early pubertal children using magnetic resonance imaging.
AB  - INTRODUCTION: Sex differences in trabecular bone microarchitecture have been
      reported in adults and adolescents, but studies in children are lacking. The
      primary aim of this study was to determine if there are sex differences in
      magnetic resonance imaging (MRI)-based measures of trabecular bone
      microarchitecture at the distal femur of children. MATERIALS AND METHODS: Pre and
      early pubertal boys (n=23) and girls (n=20) between the 5th and 95th percentiles
      for height, body mass and BMI were studied. Apparent trabecular bone volume to
      total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness
      (appTb.Th), trabecular separation (appTb.Sp) and a composite measure of
      trabecular bone microarchitecture (TBMcom) were assessed at the lateral aspect of
      the distal femur using MRI. Areal bone mineral density (aBMD), bone mineral
      content (BMC) and bone area were assessed at the distal femur using dual-energy X
      ray absorptiometry (DXA). Tanner staging was used to assess pubertal development.
      Physical activity was assessed using an accelerometry-based activity monitor.
      Calcium intake was assessed using diet records. RESULTS: There were no sex
      differences in age, height, femur length, body mass, physical activity or calcium
      intake (all P>0.05). There were no sex differences in any MRI-based measure of
      trabecular bone microarchitecture. Consistent with the MRI-based measures, there
      were no differences in aBMD, BMC or bone area from DXA at the distal femur
      (P>0.05). appBV/TV, appTb.N, appTb.Th, appTb.Sp and TBMcom were also moderately
      to strongly related to aBMD (r=0.73, 0.63, 0.51, -0.74 and 0.61, respectively,
      p<0.001) and BMC (r=0.84, 0.63, 0.66, -0.80 and 0.77, respectively, P<0.001).
      CONCLUSIONS: The findings suggest that there are no differences in measures of
      trabecular bone microarchitecture at the distal femur of pre and early pubertal
      boys and girls who are similar in size, physical activity and calcium intake.
      Future studies with larger sample sizes that cover all pubertal stages are needed
      to determine if sex differences in trabecular bone microarchitecture emerge at
      the distal femur and other weight bearing bone sites.

PMID- 21851869
TI  - Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia
      and systemic edema in the OCD rat.
AB  - Homozygous rats (ocd/ocd) of a mutant inbred strain, OCD (osteochondrodysplasia),
      show osteochondrodysplasia, systemic edema, cleft palate, protruding tongue,
      disproportionate dwarfism, and lethality immediately after birth. Their epiphyses
      show decreased levels of glycosaminoglycans and weak staining for extracellular
      matrix proteins. The epiphyseal chondrocytes have large vesicles and expanded
      endoplasmic reticulum and Golgi apparatus. These phenotypic features are
      inherited in an autosomal recessive manner, and the ocd locus responsible for
      these phenotypes has been mapped close to D11Mgh3 on rat chromosome 11. In the
      present study, we characterized the embryonic pathogenesis of ocd/ocd rats and
      identified the mutant gene. Subcutaneous edema in the dorsal portion was found at
      embryonic day (E) 16.5, and the other anomalies described above were apparent
      after E18.5 in ocd/ocd. Whole mount immunohistochemistry for Sox9 revealed that
      mesenchymal condensation was delayed in limb bud in ocd/ocd, and skeletal
      preparation showed that the progression of whole-body chondrogenesis was delayed
      in ocd/ocd. Histological and immunohistological analyses of the femur showed that
      cell proliferations of resting and proliferative zones of growth plate were
      significantly reduced in ocd/ocd embryos. Fine linkage mapping localized the ocd
      locus within 84kb of positions 65,584-65,668kb containing a part of Golgb1 gene
      on chromosome 11. Expression of Golgb1 mRNA was found in limb buds, somite
      derivatives and calvaria. Sequence analysis identified a 10-bp insertion in exon
      13 of the Golgb1 gene in ocd/ocd rats. The Golgb1 gene encodes the COPI vesicle
      tethering factor, giantin. This insertion mutation causes a frame shift, and
      introduces a premature termination codon at codon 1082, leading to truncation of
      the C-terminal two thirds of giantin. By in-gel Western analysis using anti
      giantin antibody that recognizes an epitope within 200 aa of the C-terminus, the
      expression of giantin was not detected in ocd/ocd embryos. As the C-terminal
      region of giantin is required for localization to the Golgi apparatus, these
      results strongly suggested that giantin is functionally defective in ocd/ocd
      rats. Therefore, we concluded that mutation of the Golgb1 gene is responsible for
      the phenotypic characteristics including osteochondrodysplasia of ocd/ocd, and
      that giantin plays a pivotal role in multiple aspects of chondrogenesis.

PMID- 21851870
TI  - Distribution of Pneumocystis jirovecii in lungs from colonized COPD patients.
AB  - Pneumocystis jirovecii has been detected in lung tissue from patients with
      chronic obstructive pulmonary disease (COPD) and is associated with disease
      severity. The regional distribution of the organism in lungs is unknown, but
      differences in distribution of Pneumocystis could affect estimates of
      colonization prevalence. We examined the distribution of Pneumocystis in the
      lungs of 19 non-HIV-infected patients with COPD who were undergoing lung
      transplantation. DNA was extracted from explanted lungs. We found Pneumocystis
      colonization in lung tissue of 42.1% of patients with advanced COPD; however,
      there was significant regional variation in colonization between lung segments of
      individual patients. Colonization was detected more commonly in the lower and
      middle lobes than in the upper lobes. These findings suggest that single samples
      from an individual may underestimate the prevalence of Pneumocystis colonization
      and future studies may obtain a higher yield of Pneumocystis colonization
      detection when sampling the lower lobes.

PMID- 21851872
TI  - A cluster of mucormycosis infections in hematology patients: challenges in
      investigation and control of invasive mold infections in high-risk patient
      populations.
AB  - Mucormycosis has been reported to be occurring more frequently in hematopoietic
      stem cell transplant (HSCT) recipients in recent years. We investigated a
      hospital cluster of mucormycosis cases among patients with hematologic disorders.
      Case-patients were identified through hospital microbiology and pathology
      database searches and compared to randomly selected controls matched on
      underlying disease and hospital discharge date using conditional logistic
      regression. Environmental assessments, including collection of samples for fungal
      cultures, were performed. Of 11 case-patients, 6 (55%) had acute myelogenous
      leukemia and 3 (27%) were allogeneic HSCT recipients. Five case-patients (45%)
      died. In univariate analysis, case-patients were more likely than controls to
      have refractory hematologic disease (odds ratio [OR], 13.75; 95% confidence
      interval [CI], 1.31-689); neutropenia >14 days (OR, 11.50; 95% CI, 1.27-558) or
      to have received voriconazole prophylaxis (OR, 11.26; 95% CI, 1.11-infinity). A
      point source was not identified. Factors such as underlying disease state and
      antifungal prophylaxis type may identify hematology patients at highest risk for
      mucormycosis. Our investigation highlighted critical knowledge gaps, including
      strain typing methods, the role of the hospital environment in mucormycosis
      outbreaks, and hospital environmental infection control measures most likely to
      reduce exposure of immunosuppressed persons to mucormycetes.

PMID- 21851871
TI  - Diagnosis of tuberculosis infection by tuberculin skin test and a whole-blood
      interferon-gamma release assay in patients considered for anti-tumor necrosis
      factor-alpha therapy.
AB  - To assess the performance of QuantiFERON(r)-TB Gold in-Tube (QFT-GIT; Cellestis,
      Carnegie, Australia) and tuberculin skin test (TST) in patients with immune
      mediated inflammatory diseases (IMID), before anti-tumor necrosis factor-alpha
      (TNF-alpha) therapy, and to compare the results with those from the healthy
      population. Three hundred fourteen subjects (214 with IMID and 100 controls)
      underwent simultaneous QFT-GIT and TST. QFT-GIT was positive in 21% of IMID
      patients and in 16% of controls (P = 0.29). Among IMID patients, 21% tested
      positive by QFT-GIT and 24%, by TST (P = 0.30). Positive QFT-GIT results were not
      affected by immunosuppressive therapy (odds ratio, 0.78; 95% confidence interval
      [CI], 0.36-1.68; P = 0.52). Agreement between both tests in those patients who
      tested positive by one of the tests was 50% (95% CI, 37.2-62.8). QFT-GIT is
      useful for identifying IMID patients requiring treatment of latent tuberculosis
      before anti-TNF therapy. However, given the poor agreement between TST and QFT
      GIT, we advocate a strategy of simultaneous testing to optimize diagnostic
      sensitivity.

PMID- 21851873
TI  - Update on the telavancin activity tested against European staphylococcal clinical
      isolates (2009-2010).
AB  - This study evaluated telavancin activity against 3868 Staphylococcus aureus and
      1003 coagulase-negative staphylococci (CoNS) collected from 33 European hospitals
      (2009-2010). Studies of telavancin potency included analysis of strains with
      decreased susceptibility to glycopeptides. Telavancin (MIC(50/90), 0.12/0.25
      MUg/mL) showed high activity against S. aureus and CoNS, regardless of the
      stratification analysis performed (year sampled, infection source, or methicillin
      susceptibility). In addition, telavancin (MIC(50/90), 0.25/0.5 MUg/mL) retained
      activity against S. aureus isolates with higher vancomycin (MIC, 2 MUg/mL) or
      teicoplanin (MIC, 2-8 MUg/mL) MIC results. Overall, telavancin exhibited higher
      potency (at least 2-fold greater) than tested comparators (vancomycin,
      daptomycin, and linezolid) against European staphylococci. Alongside published
      clinical data, the telavancin in vitro activity observed against these pathogens
      supports this drug as an option for treating S. aureus infections in Europe,
      including those infections caused by strains with decreased susceptibility to
      vancomycin and/or teicoplanin.

PMID- 21851874
TI  - Computed tomography and angiography of left ventricular diverticulum.

PMID- 21851875
TI  - Device therapy in heart failure patients with chronic kidney disease.
AB  - Heart failure (HF) and chronic kidney disease (CKD) both carry significant risk
      for sudden cardiac death, hospitalization, and mortality; when combined, however,
      they markedly increase the risk of morbidity and mortality. Device therapies such
      as implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization
      therapy (CRT) are treatments proven to have significant benefit on clinical
      outcomes in select patients with HF. However, the majority of studies supporting
      the use of these devices have limited data on patients with CKD or end-stage
      renal disease. In this review, we discuss the intersection of HF and CKD as it
      relates to progressive HF and the risk of sudden death. Although these disorders
      are common and have a poor prognosis, the evidence available for guiding
      treatment decisions for the use of ICD and CRT devices in these patients is
      lacking. Given this lack of clear evidence, pragmatic clinical trials and
      comparative effectiveness studies are needed to help identify the appropriate use
      of ICD and CRT devices in this high-risk population of patients with HF and CKD.

PMID- 21851876
TI  - Results of low-dose human atrial natriuretic peptide infusion in nondialysis
      patients with chronic kidney disease undergoing coronary artery bypass grafting:
      the NU-HIT (Nihon University working group study of low-dose HANP Infusion
      Therapy during cardiac surgery) trial for CKD.
AB  - OBJECTIVES: The purpose of this comparative study is to prove the efficacy of the
      human atrial natriuretic peptide (hANP) in patients with chronic kidney disease
      (CKD) undergoing coronary artery bypass graft surgery (CABG). BACKGROUND: CKD is
      an important risk factor for cardiac surgery. METHODS: This was a randomized
      controlled study of 303 patients with CKD who underwent CABG, and were divided
      into a group who received carperitide infusion and another group without
      carperitide. The primary endpoints were: 1) the post-operative dialysis-free
      rate; and 2) serum creatinine (sCr) and estimated glomerular filtration rate. The
      secondary endpoints were: 1) the early post-operative outcome; 2) outcome at 1
      year post-operatively; 3) the maximum sCr, the rate of increase of sCr, and an
      increase of sCr by >= 0.3 mg/dl compared with the pre-operative value; and 4) ANP
      and cyclic-guanosine monophosphate levels. RESULTS: The post-operative sCr was
      significantly lower in the hANP group not only in the post-operative acute stage
      but also in the first year. The maximum Cr and Cr increase rate were
      significantly lower in the hANP group (p = 0.00665, p < 0.0001). There was no
      difference in mortality rate in the first year post-operatively, and fewer
      cardiac events and patients going on dialysis were found in the hANP group (p <
      0.0001 and p = 0.0014, respectively). CONCLUSIONS: In the post-operative acute
      stage, carperitide showed cardiorenal protective effects that prevented post
      operative cardiac events and initiation of dialysis. Thus, perioperative infusion
      of low-dose carperitide may have a significant role in management of patients
      with renal dysfunction undergoing on-pump CABG. (Effectiveness of hANP for
      Cardiac Surgery in Patients With Moderate to Severe Preoperative Renal
      Dysfunction Without Dialysis [NU-HIT for CRF]; UMIN000001462).

PMID- 21851877
TI  - Natriuretic peptides renal protective after all?

PMID- 21851878
TI  - Renal function-based contrast dosing to define safe limits of radiographic
      contrast media in patients undergoing percutaneous coronary interventions.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between
      calculated creatinine clearance (CCC)-based contrast dose and renal complications
      in patients undergoing percutaneous coronary interventions (PCI). BACKGROUND:
      Excess volumes of contrast media are associated with renal complications in
      patients undergoing cardiac procedures. Because contrast media are excreted by
      the kidney, we hypothesized that a dose estimation on the basis of CCC would
      provide a simple strategy to define a safe dose of contrast media. METHODS: We
      assessed the association between CCC-based contrast dose and the risk of contrast
      induced nephropathy (CIN) and need for in-hospital dialysis in 58,957 patients
      undergoing PCI and enrolled in the BMC2 (Blue Cross Blue Shield of Michigan
      Cardiovascular Consortium) registry from 2007 to 2008. Patients receiving
      dialysis at the time of the procedure were excluded. RESULTS: The risk of CIN and
      nephropathy requiring dialysis (NRD) was directly associated with increasing
      contrast volume adjusted for renal function. The risk for CIN and NRD approached
      significance when the ratio of contrast dose/CCC exceeded 2 (adjusted odds ratio
      [OR] for CIN: 1.16, 95% confidence interval [CI]: 0.98 to 1.37, adjusted OR for
      NRD: 1.72, 95% CI: 0.9 to 3.27) and was dramatically elevated in patients
      exceeding a contrast to CCC ratio of 3 (adjusted OR for CIN: 1.46, 95% CI: 1.27
      to 1.66, adjusted OR for NRD: 1.89, 95% CI: 1.21 to 2.94). CONCLUSIONS: Our study
      supports the need for minimizing contrast dose in patients with renal
      dysfunction. A contrast dose on the basis of estimated renal function with a
      planned contrast volume restricted to less than thrice and preferably twice the
      CCC might be valuable in reducing the risk of CIN and NRD.

PMID- 21851879
TI  - Influence of global region on outcomes in heart failure beta-blocker trials.
AB  - OBJECTIVES: We sought to describe the United States and the rest of the world
      (ROW) outcomes from the major beta-blocker heart failure (HF) trials. BACKGROUND:
      HF trials have demonstrated differences in outcomes by geographic region.
      METHODS: Randomized, double-blind, placebo-controlled studies that evaluated beta
      blockers in HF patients, had a primary endpoint of mortality, and enrolled U.S.
      patients were included. Relative risk (RR) was calculated for patients enrolled
      in the United States and ROW. Meta-analysis of the combined mortality rates was
      performed using the Cochran-Mantel-Haenszel statistic, stratified by study.
      RESULTS: A total of 8,988 patients were enrolled in the MERIT-HF (Metoprolol
      Controlled-Release Randomized Intervention Trial in Heart Failure), COPERNICUS
      (Carvedilol Prospective Randomized Cumulative Survival trial), and BEST (beta
      Blocker Evaluation of Survival Trial) combined; 4,198 (46.7%) were from the
      United States. In the U.S. cohort, the RR reduction for each beta-blocker was of
      smaller magnitude than in the overall cohort and no longer significant, whereas
      in the ROW subgroup, the mortality benefit for beta-blockade persisted. In the
      pooled analysis (n = 11,635), the RR of death was reduced by 23% (p < 0.001) with
      beta-blockade compared with placebo. In contrast, the mortality reduction
      associated with beta-blockade in the U.S. cohort was small and not statistically
      significant (RR: 0.92, 95% confidence interval [CI]: 0.82 to 1.02, p = 0.11). The
      survival benefit persisted in the ROW cohort (RR: 0.64, 95% CI: 0.56 to 0.72, p <
      0.001). CONCLUSIONS: Among patients enrolled in the United States, beta-blockade
      was associated with a lower magnitude of survival benefit, whereas the ROW
      response was similar to the total study population. This geographic difference in
      treatment response may be a reflection of population differences, genetics,
      cultural or social differences in disease management, or low power and
      statistical chance.

PMID- 21851880
TI  - Globalization of clinical trials how should we interpret differences in outcomes?

PMID- 21851881
TI  - Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies
      caused by dystrophin defects.
AB  - OBJECTIVES: We sought to describe the diagnostic work-up, phenotype, and long
      term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS)
      defects. BACKGROUND: X-linked DCM associated with DYS defects can be clinically
      indistinguishable from other types of DCM. METHODS: The series comprises 436
      consecutive male patients diagnosed with DCM. Patients underwent endomyocardial
      biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and
      multiple ligation dependent probe assay for deletions and direct sequencing of
      the 79 exons and flanking regions of the gene for point mutations or small
      rearrangements. RESULTS: We identified DYS defects in 34 of 436 patients (7.8%)
      (onset age 34 +/- 11 years, age range 17 to 54 years); 30 had proven X-linked
      inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or
      increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB
      showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame
      deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site
      mutation. During a median follow-up of 60 months (interquartile range: 11.25 to
      101.34 months) we observed 17 events, all related to heart failure (HF) (median
      event-free survival: 83.5 months). Eight patients (23%) underwent
      transplantation, and 9 (26%) died of HF while waiting for transplantation. Eight
      patients received an implantable cardioverter-defibrillator, although none had
      device intervention during a median follow-up of 14 months (interquartile range:
      5 to 25 months). No patient died suddenly, suffered syncope, or developed life
      threatening ventricular arrhythmias. CONCLUSIONS: DYS-related DCM should be
      suspected in male patients with increased serum creatine phosphokinase (82%) and
      X-linked inheritance. The disease shows a high risk of end-stage HF but a lower
      risk of life-threatening arrhythmias.

PMID- 21851882
TI  - Cardiac resynchronization therapy in patients with minimal heart failure: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to perform a systematic review and meta
      analysis of prospective randomized clinical trials of cardiac resynchronization
      therapy (CRT) versus implantable cardioverter-defibrillator (ICD) in patients
      with reduced ejection fraction (EF), prolonged QRS interval, and New York Heart
      Association (NYHA) functional class I to II heart failure (HF). BACKGROUND: In
      patients with advanced HF, CRT improves left ventricular (LV) function and
      reduces mortality and hospitalizations. Recent data suggest that patients with
      milder HF also benefit from CRT. METHODS: A meta-analysis of 5 clinical trials
      including 4,317 patients with NYHA functional class I/II HF was performed.
      RESULTS: Average age of patients was 65 years, and 80% were male. Frequency of
      all-cause mortality for CRT versus ICD was 8% versus 11.5% (risk ratio [RR]:
      0.81; 95% confidence interval [CI]: 0.65 to 0.99, p = 0.04); for HF
      hospitalization, it was 11.6% versus 18.2% (RR: 0.68; 95% CI: 0.59 to 0.79, p <
      0.001). Patients assigned to CRT had a significantly greater improvement in LVEF
      (+5.9% vs. +2.2%, p < 0.001) and LV volume than ICD patients. Among mildly
      symptomatic (NYHA functional class II) patients, CRT was associated with
      significantly lower mortality and HF hospitalization (RR: 0.73; 95% CI: 0.64 to
      0.83), p < 0.001). In asymptomatic (NYHA functional class I) patients, HF
      hospitalization risk was lower (RR: 0.57; 95% CI: 0.34 to 0.97, p = 0.04) with
      CRT; however, there was no difference in mortality. Twelve asymptomatic HF
      patients needed to be treated with CRT to prevent 1 hospitalization. CONCLUSIONS:
      Cardiac resynchronization therapy decreases all-cause mortality, reduces HF
      hospitalizations, and improves LVEF in NYHA functional class I/II HF patients.
      Although there was a reduction in HF hospitalization with CRT for asymptomatic
      (NYHA functional class I) patients, risks versus benefits have to be carefully
      considered in this subgroup.

PMID- 21851884
TI  - Lenient versus strict rate control in atrial fibrillation some devils in the
      details.

PMID- 21851885
TI  - Diastolic dysfunction in patients undergoing cardiac surgery: a
      pathophysiological mechanism underlying the initiation of new-onset post
      operative atrial fibrillation.
AB  - OBJECTIVES: Our goal was to investigate whether left ventricular (LV) diastolic
      dysfunction was an important pathophysiological mechanism underlying the
      initiation of new-onset post-operative atrial fibrillation (POAF). BACKGROUND:
      Atrial fibrillation is a common complication after cardiac surgery. However, the
      precise mechanism underlying its development remains poorly understood. Pre
      existing alterations of myocardial diastolic function may predispose patients to
      the development of POAF. METHODS: Patients were residents of Olmsted County,
      Minnesota, who underwent complete LV diastolic function assessment before
      coronary artery bypass grafting and/or valve surgery between January 1, 2000, and
      December 31, 2005. All were in sinus rhythm and had no history of atrial
      fibrillation, a pacemaker, mitral stenosis, or congenital heart disease. POAF was
      defined as any episode of atrial fibrillation within 30 days after surgery.
      RESULTS: POAF occurred in 135 of 351 patients (38.5%). Patients with POAF were
      older (mean age 72.5 +/- 10.3 years vs. 63.1 +/- 14.1 years; p < 0.001) and more
      likely to have abnormal diastolic function. The rate of POAF increased
      exponentially with diastolic function grade (DFG) severity (p < 0.001). By
      multivariate analysis, after adjusting for clinical and surgical risk factors,
      independent predictors of POAF were older age (odds ratio [OR]: 1.05; p < 0.001),
      higher body mass index (OR: 1.06; p = 0.03), and abnormal LV DFG (DFG 1, OR: 5.12
      [p = 0.006]; DFG 2, OR: 9.87 [p < 0.001]; and DFG 3, OR: 28.52 [p < 0.001]).
      CONCLUSIONS: LV diastolic dysfunction is a powerful, independent predisposing
      substrate for the initiation of POAF. Evaluation may be useful during risk
      stratification of patients undergoing cardiac surgery.

PMID- 21851883
TI  - Effect of lenient versus strict rate control on cardiac remodeling in patients
      with atrial fibrillation data of the RACE II (RAte Control Efficacy in permanent
      atrial fibrillation II) study.
AB  - OBJECTIVES: The aim of this study was to evaluate echocardiographic remodeling in
      permanent atrial fibrillation (AF) patients treated with either lenient or strict
      rate control. BACKGROUND: It is unknown whether in permanent AF, lenient rate
      control is associated with more adverse cardiac remodeling than strict rate
      control. METHODS: Echocardiography was conducted at baseline and at follow-up in
      517 patients included in the RACE II (RAte Control Efficacy in permanent atrial
      fibrillation II) trial. Echocardiographic parameters were compared between
      patients randomized to lenient rate control (n = 261) or strict rate control (n =
      256). RESULTS: Baseline echocardiographic parameters were comparable between
      patients randomized to lenient and strict rate control. Between baseline and
      follow-up, significant adverse atrial or ventricular remodeling was not observed
      in either group. There were also no significant differences in atrial and
      ventricular remodeling between patients who continuously had heart rates between
      80 and 110 beats/min and patients who continuously had heart rates <80 beats/min
      during follow-up. Lenient rate control was not independently associated with
      changes in echocardiographic parameters: mean adjusted effect on left atrial size
      was 1.6 mm (p = 0.09) and 1.1 mm on left ventricular end-diastolic diameter (p =
      0.23). Instead, female sex was independently associated with adverse remodeling:
      mean adjusted effect on left atrial size was 2.4 mm (p = 0.02) and 6.5 mm on left
      ventricular end-diastolic diameter (p < 0.0001). CONCLUSIONS: Female sex, not
      lenient rate control, seemed to be associated with significant adverse cardiac
      remodeling in patients with permanent AF such as those enrolled in the RACE II
      study. (RAte Control Efficacy in Permanent Atrial Fibrillation [RACE II];
      NCT00392613).

PMID- 21851886
TI  - Valvular aortic stenosis as a major sequelae in patients with pre-existing
      subaortic stenosis changing spectrum of outcomes.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence of valvular
      aortic stenosis requiring surgery in patients with a pre-existing diagnosis of
      subaortic stenosis. BACKGROUND: Classic teachings emphasize aortic regurgitation
      as the most common complication associated with discrete subaortic stenosis. We
      hypothesized that significant aortic stenosis may also be an important valve
      lesion associated with this condition. METHODS: Clinical outcomes in patients
      with subaortic stenosis were examined. The primary outcome of interest was the
      prevalence of valvular aortic stenosis requiring surgery (surgical valvotomy or
      valve replacement). Logistic regression was used to identify variables associated
      with the need for surgery for aortic stenosis. RESULTS: One hundred twenty-one
      adults with subaortic stenosis (median age 32 years) were evaluated in our
      clinic. Associated lesions were common: 23% had bicuspid valves and 21% had
      coarctation of the aorta. Seventy-nine percent of the patients had at least 1
      surgical resection of subaortic tissue (median age 12 years). Moderate to severe
      aortic regurgitation was present in 16% of patients (19 of 121), 3 of whom
      required surgical intervention in adulthood. Twenty-six percent of patients (32
      of 121) required surgery for valvular aortic stenosis. Valve surgery for aortic
      stenosis was more common in patients with concomitant bicuspid aortic valve
      disease (p = 0.008), coarctation of the aorta (p = 0.03), and supravalvular
      stenosis (p = 0.02). CONCLUSIONS: Valvular aortic stenosis is a surprisingly
      common finding in patients with discrete subaortic stenosis. Careful clinical
      follow-up of this population to monitor aortic valve status continues to be
      warranted even after a successful surgical resection.

PMID- 21851887
TI  - S100A1 genetically targeted therapy reverses dysfunction of human failing
      cardiomyocytes.
AB  - OBJECTIVES: This study investigated the hypothesis whether S100A1 gene therapy
      can improve pathological key features in human failing ventricular cardiomyocytes
      (HFCMs). BACKGROUND: Depletion of the Ca2+-sensor protein S100A1 drives
      deterioration of cardiac performance toward heart failure (HF) in experimental
      animal models. Targeted repair of this molecular defect by cardiac-specific
      S100A1 gene therapy rescued cardiac performance, raising the immanent question of
      its effects in human failing myocardium. METHODS: Enzymatically isolated HFCMs
      from hearts with severe systolic HF were subjected to S100A1 and control
      adenoviral gene transfer and contractile performance, calcium handling,
      signaling, and energy homeostasis were analyzed by video-edge-detection, FURA2
      based epifluorescent microscopy, phosphorylation site-specific antibodies, and
      mitochondrial assays, respectively. RESULTS: Genetically targeted therapy
      employing the human S100A1 cDNA normalized decreased S100A1 protein levels in
      HFCMs, reversed both contractile dysfunction and negative force-frequency
      relationship, and improved contractile reserve under beta-adrenergic receptor
      (beta-AR) stimulation independent of cAMP-dependent (PKA) and calmodulin
      dependent (CaMKII) kinase activity. S100A1 reversed underlying Ca2+ handling
      abnormalities basally and under beta-AR stimulation shown by improved SR Ca2+
      handling, intracellular Ca2+ transients, diastolic Ca2+ overload, and diminished
      susceptibility to arrhythmogenic SR Ca2+ leak, respectively. Moreover, S100A1
      ameliorated compromised mitochondrial function and restored the
      phosphocreatine/adenosine-triphosphate ratio. CONCLUSIONS: Our results
      demonstrate for the first time the therapeutic efficacy of genetically
      reconstituted S100A1 protein levels in HFCMs by reversing pathophysiological
      features that characterize human failing myocardium. Our findings close a gap in
      our understanding of S100A1's effects in human cardiomyocytes and strengthen the
      rationale for future molecular-guided therapy of human HF.

PMID- 21851888
TI  - S100A1: Another Step Toward Therapeutic Development for Heart Failure.

PMID- 21851889
TI  - A case of all 3 coronary to bronchial arteries fistulas.

PMID- 21851890
TI  - Efficiency of atorvastatin in the protection of anthracycline-induced
      cardiomyopathy.

PMID- 21851891
TI  - The Israel screening failure analyzing the data to understand the results.

PMID- 21851892
TI  - Media reporting bias affects reported sudden death rates.

PMID- 21851895
TI  - Saphenous vein graft intervention.
AB  - Saphenous vein grafts are commonly used conduits for surgical revascularization
      of coronary arteries but are associated with poor long-term patency rates.
      Percutaneous revascularization of saphenous vein grafts is associated with worse
      clinical outcomes including higher rates of in-stent restenosis, target vessel
      revascularization, myocardial infarction, and death compared with percutaneous
      coronary intervention of native coronary arteries. Use of embolic protection
      devices is a Class I indication according to the American College of
      Cardiology/American Heart Association guidelines to decrease the risk of distal
      embolization, no-reflow, and periprocedural myocardial infarction. Nonetheless,
      these devices are underused in clinical practice. Various pharmacological agents
      are available that may also reduce the risk of or mitigate the consequences of no
      reflow. Covered stents do not decrease the rates of periprocedural myocardial
      infarction and restenosis. Most available evidence supports treatment with drug
      eluting stents in this high-risk lesion subset to reduce angiographic and
      clinical restenosis, although large, randomized trials comparing drug-eluting
      stents and bare-metal stents are needed.

PMID- 21851896
TI  - Percutaneous coronary intervention in native arteries versus bypass grafts in
      prior coronary artery bypass grafting patients: a report from the National
      Cardiovascular Data Registry.
AB  - OBJECTIVES: This study examined a large registry to determine the frequency,
      predictors, and outcomes of native coronary artery versus bypass graft
      percutaneous coronary intervention (PCI) in patients with prior coronary artery
      bypass graft surgery (CABG). BACKGROUND: The PCI target vessel and corresponding
      outcomes in prior CABG patients are poorly studied. METHODS: We analyzed the
      frequency and factors associated with native versus bypass graft PCI in prior
      CABG patients undergoing PCI between January 1, 2004, and June 30, 2009, in the
      National Cardiovascular Data Registry (NCDR) CathPCI Registry. Generalized
      estimating equations logistic regression modeling was used to generate
      independent variables associated with native versus bypass graft PCI and in
      hospital mortality. RESULTS: During the study period, PCI in prior CABG patients
      represented 17.5% of the total PCI volume (300,902 of 1,721,046). The PCI target
      was a native coronary artery in 62.5% and a bypass graft in 37.5%: saphenous vein
      graft (SVG) (104,678 [34.9%]), arterial graft (7,517 [2.5%]), or both arterial
      graft and SVG (718 [0.2%]). Compared with patients undergoing native coronary
      artery PCI, those undergoing bypass graft PCI had higher-risk characteristics and
      more procedural complications. On multivariable analysis, several parameters
      (including graft stenosis and longer interval from CABG) were associated with
      performing native coronary PCI, and bypass graft PCI was associated with higher
      in-hospital mortality (adjusted odds ratio: 1.22, 95% confidence interval: 1.12
      to 1.32). CONCLUSIONS: Most PCIs performed in prior CABG patients are done in
      native coronary artery lesions. Compared with native coronary PCI, bypass graft
      PCI is independently associated with higher in-hospital mortality.

PMID- 21851898
TI  - Getting safely in and out of a transcatheter aortic valve implantation procedure
      vascular complications according to the valvular academic research consortium
      criteria.

PMID- 21851897
TI  - Transfemoral aortic valve implantation new criteria to predict vascular
      complications.
AB  - OBJECTIVES: This study sought to evaluate the incidence, impact, and predictors
      of vascular complications in transcatheter aortic valve implantation (TAVI).
      BACKGROUND: Vascular complications increase morbidity and mortality in
      transfemoral TAVI; however, there remains a paucity of data describing these
      serious events. METHODS: We performed a prospective cohort study of 130
      consecutive transfemoral TAVI recipients. Vascular complications were defined by
      the Valve Academic Research Consortium (VARC) criteria. The ratio of the sheath
      outer diameter (in millimeters) to the minimal femoral artery diameter (in
      millimeters) defined the sheath to femoral artery ratio (SFAR). RESULTS: In our
      cohort of elderly patients (83.3 +/- 5.9 years), the logistic EuroScore was 25.8%
      +/- 11.9%. The Edwards valve was used in 102 cases (18- to 24-F) and the
      CoreValve in 27 (18-F). The minimal femoral artery diameter was 8.17 +/- 1.14 mm,
      and the calcification (0 to 3) and tortuosity scores (0 to 3) were 0.58 +/- 0.72
      and 0.28 +/- 0.53, respectively. The mean sheath diameter was 8.10 +/- 0.82 mm,
      and the mean SFAR was 0.99 +/- 0.16. Vascular complications occurred in 27.6%
      (VARC major: 17.3%, minor: 10.2%), and major vascular complications predicted 30
      day mortality (22.7% vs. 7.6%, p = 0.049). The SFAR (hazard ratio [HR]: 186.20,
      95% confidence interval [CI]: 4.41 to 7,855.11), center experience (HR: 3.66, 95%
      CI: 1.17 to 11.49), and femoral calcification (HR: 3.44, 95% CI: 1.16 to 10.17)
      predicted major complications by multivariate analysis. An SFAR threshold of 1.05
      (area under the curve = 0.727) predicted a higher rate of VARC major
      complications (30.9% vs. 6.9%, p = 0.001) and 30-day mortality (18.2% vs. 4.2%, p
      = 0.016). CONCLUSIONS: Vascular complications in transfemoral TAVI are relatively
      frequent. VARC major vascular complications increase 30-day mortality and are
      predicted by experience, femoral calcification, and SFAR. Routine application of
      SFAR will improve patient selection for transfemoral TAVI and may improve
      outcome.

PMID- 21851899
TI  - Clinical outcomes using a new crossover balloon occlusion technique for
      percutaneous closure after transfemoral aortic valve implantation.
AB  - OBJECTIVES: This study sought to evaluate the technical success and clinical
      outcomes of an adjunctive crossover balloon occlusion technique (CBOT) combined
      with the 10-F Prostar percutaneous closure device (PCD) on the incidence of
      vascular and bleeding complications in patients after transfemoral transcatheter
      aortic valve implantation (TAVI). BACKGROUND: Vascular closure following large
      vessel access has most commonly been performed using a surgical cut-down and
      repair procedure. METHODS: Between November 2008 and September 2010, 58
      consecutive patients with severe aortic stenosis underwent TAVI via a retrograde
      femoral artery approach using the Edwards-SAPIEN transcatheter valve. Among these
      patients, 56 were treated with a CBOT using the "pre-close" technique and the 10
      F Prostar system. The technical success of this new CBOT and the 30-day frequency
      of clinical events, including all-cause mortality, major vascular complications,
      and major bleeding (defined according to a modified version of the Valve Academic
      Research Consortium criteria), were assessed. RESULTS: Successful closure was
      obtained in all but 3 patients (94.6%). The 30-day frequencies of mortality,
      major vascular complications, and major bleeding were 7.1%, 14.3%, and 5.4%
      respectively. No deaths were directly related to access site complications.
      Fourteen patients (25%) received at least 1 transfusion during the index
      hospitalization, of which 8 (57.1%) were not related to vascular complications.
      The mean and median hospital lengths of stay were 7.8 and 6.0 days. CONCLUSIONS:
      This new percutaneous adjunctive CBOT combined with the Prostar PCD resulted in
      controlled, safe, and successful percutaneous closure in most patients after
      TAVI.

PMID- 21851900
TI  - Clinical experience with percutaneous left ventricular transapical access for
      interventions in structural heart defects a safe access and secure exit.
AB  - OBJECTIVES: This study sought to evaluate the safety of percutaneous direct left
      ventricular access for interventional procedures. BACKGROUND: Experience with
      percutaneous access of the left ventricle (LV) for interventional procedures has
      been limited and associated with a high percentage of major complications. We
      report our clinical experience with percutaneous direct LV access for
      interventional procedures. METHODS: Between March 2008 and December 2010, there
      were 32 percutaneous transapical punctures in 28 consecutive patients (16 males,
      mean age 68.2 +/- 10.8 years). The delivery sheath sizes ranged from 5- to 12-F.
      RESULTS: All transapical punctures were successfully performed, and safe closure
      of the access sites was achieved. Total procedural time was 153.6 +/- 49.4 min
      for procedures converted from conventional approaches to a transapical approach,
      129.5 +/- 29.6 min for the transapical approach with trans-septal rail support,
      and 109.3 +/- 41.4 min for the planned transapical approach. Fluoroscopy time was
      61.3 +/- 26.1 min, 29.7 +/- 20.8 min, and 27.4 +/- 21.4 min, respectively.
      Fluoroscopy time for closure of mitral paravalvular leaks was reduced by 35%,
      from 42.6 +/- 29.9 min to 27.4 +/- 15.6 min. Complications were observed in 2
      patients (7.1%). CONCLUSIONS: With meticulous planning, transapical puncture is
      safe. The transapical access provides a more direct approach to the LV targets
      for intervention and leads to a significant decrease in the procedural and
      fluoroscopy times. Device closure of the direct LV access site is a reliable and
      safe method of hemostasis. Placement of a closure device should be considered if
      sheaths larger than 5-F are used. Although we used this technique only for
      paravalvular leak and LV pseudoaneurysm closure, it may have application for
      other percutaneous structural heart interventions.

PMID- 21851901
TI  - The left ventricular apex opening and closing a new port into the human heart.

PMID- 21851902
TI  - The pre-hospital fibrinolysis experience in Europe and North America and
      implications for wider dissemination.
AB  - OBJECTIVES: The primary objective of this report was to describe the
      infrastructures and processes of selected European and North American pre
      hospital fibrinolysis (PHL) programs. A secondary objective is to report the
      outcome data of the PHL programs surveyed. BACKGROUND: Despite its benefit in
      reducing mortality in patients with ST-segment elevation myocardial infarction,
      PHL remained underused in North America. Examination of existing programs may
      provide insights to help address barriers to the implementation of PHL. METHODS:
      The leading investigators of PHL research projects/national registries were
      invited to respond to a survey on the organization and outcomes of their
      affiliated PHL programs. RESULTS: PHL was successfully deployed in a wide range
      of geographic territories (Europe: France, Sweden, Vienna, England, and Wales;
      North America: Houston, Edmonton, and Nova Scotia) and was delivered by
      healthcare professionals of varying expertise. In-hospital major adverse outcomes
      were rare with mortality of 3% to 6%, reinfarction of 2% to 5%, and stroke of
      <2%. CONCLUSIONS: Combining formal protocols for PHL for some patients with
      direct transportation of others to a percutaneous coronary intervention hospital
      for primary percutaneous coronary intervention would allow for tailored
      reperfusion therapy for patients with ST-segment elevation myocardial infarction.
      Insights from a variety of international settings may promote widespread use of
      PHL and increase timely coronary reperfusion worldwide.

PMID- 21851903
TI  - Is there a role for pre-hospital fibrinolysis in North America?

PMID- 21851904
TI  - 2-year clinical follow-up from the randomized comparison of biolimus-eluting
      stents with biodegradable polymer and sirolimus-eluting stents with durable
      polymer in routine clinical practice.
AB  - OBJECTIVES: This study sought to investigate safety and efficacy of biolimus
      eluting stents (BES) with biodegradable polymer as compared with sirolimus
      eluting stents (SES) with durable polymer through 2 years of follow-up.
      BACKGROUND: BES with a biodegradable polymer provide similar efficacy and safety
      as SES with a durable polymer at 9 months. Clinical outcomes beyond the period of
      biodegradation of the polymer used for drug release and after discontinuation of
      dual antiplatelet therapy are of particular interest. METHODS: A total of 1,707
      patients were randomized to unrestricted use of BES (n = 857) or SES (n = 850) in
      an all-comers patient population. RESULTS: At 2 years, BES remained noninferior
      compared with SES for the primary endpoint, which was a composite of cardiac
      death, myocardial infarction, or clinically indicated target vessel
      revascularization (BES 12.8% vs. SES 15.2%, hazard ratio [HR]: 0.84, 95%
      confidence interval [CI]: 0.65 to 1.08, p(noninferiority) < 0.0001,
      p(superiority) = 0.18). Rates of cardiac death (3.2% vs. 3.9%, HR: 0.81, 95% CI:
      0.49 to 1.35, p = 0.42), myocardial infarction (6.3% vs. 5.6%, HR: 1.12, 95% CI:
      0.76 to 1.65, p = 0.56), and clinically indicated target vessel revascularization
      (7.5% vs. 8.6%, HR: 0.86, 95% CI: 0.62 to 1.20, p = 0.38) were similar for BES
      and SES. The rate of definite stent thrombosis through 2 years was 2.2% for BES
      and 2.5% for SES (p = 0.73). For the period between 1 and 2 years, event rates
      for definite stent thrombosis were 0.2% for BES and 0.5% for SES (p = 0.42).
      After discontinuation of dual antiplatelet therapy, no very late definite stent
      thrombosis occurred in the BES group. CONCLUSIONS: At 2 years of follow-up, the
      unrestricted use of BES with a biodegradable polymer maintained a similar safety
      and efficacy profile as SES with a durable polymer. (Limus Eluted From a Durable
      Versus Erodable Stent Coating [LEADERS]; NCT00389220).

PMID- 21851905
TI  - 1-year outcome of TRIAS HR (TRI-stent adjudication study-high risk of restenosis)
      a multicenter, randomized trial comparing genous endothelial progenitor cell
      capturing stents with drug-eluting stents.
AB  - OBJECTIVES: This study sought to demonstrate the noninferiority of endothelial
      progenitor cell capturing stents (ECS) relative to drug-eluting stents (DES)
      regarding target lesion failure (TLF) and the composite of cardiac death,
      myocardial infarction, and target lesion repeat revascularization within 1 year.
      BACKGROUND: A "pro-healing" approach for prevention of in-stent restenosis is
      theoretically favorable over the use of cytotoxic/cytostatic drugs released from
      DES to treat coronary artery disease. Promoting accelerated endothelialization of
      the stent, ECS have shown promising results in studies with patients carrying
      noncomplex lesions. METHODS: We undertook an international, clinical trial in 26
      centers planning to randomize 1,300 patients with stable coronary artery disease
      and with a high risk of restenosis between treatment, with either ECS or DES.
      After a routine review with 50% of the patients enrolled, early cessation of the
      trial was recommended by the data and safety monitoring board when TLF in the ECS
      population was higher and treatment of new patients with an ECS would be
      unreasonable. RESULTS: At 1 year evaluating 304 patients receiving ECS and 318
      receiving DES, TLF occurred in 17.4% of the ECS-treated patients and in 7.0% of
      the DES-treated patients (p = 0.98 for noninferiority). CONCLUSIONS: Within 1
      year, inhibition of intimal hyperplasia by the ECS is not sufficiently strong to
      compete with DES in terms of restenosis prevention in patients/lesions with a
      high risk of restenosis. Furthermore, long-term follow-up is pivotal to fully
      appreciate the clinical value of ECS, including the effect on late intimal
      hyperplasia regression.

PMID- 21851906
TI  - Impact of pentoxifylline on platelet function profiles in patients with type 2
      diabetes mellitus and coronary artery disease on dual antiplatelet therapy with
      aspirin and clopidogrel.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of the
      phosphodiesterase (PDE) inhibitor pentoxifylline on platelet function profiles in
      patients receiving dual antiplatelet therapy (DAPT). BACKGROUND: Previous studies
      have shown that, in patients receiving DAPT, the adjunctive use of a PDE
      inhibitor enhances platelet inhibition, particularly in those presenting with
      diabetes mellitus (DM). However, the pharmacodynamic (PD) effects of the PDE
      inhibitor pentoxifylline on platelet function profiles in DM patients receiving
      DAPT are unknown. METHODS: This was a prospective, randomized, double-blind,
      parallel design study conducted in DM patients with stable coronary artery
      disease receiving DAPT. Patients were randomly assigned to either pentoxifylline
      400 mg or placebo 3 times daily for 14 days. The PD effects were assessed by
      vasodilator-stimulated phosphoprotein phosphorylation assay, light transmittance
      aggregometry, VerifyNow P2Y12 assay (Accumetric, Inc., San Diego, California),
      and multiple electrode aggregometry at baseline and 14 days. The PD effects were
      also assessed according the presence or absence of high on-treatment platelet
      reactivity status. RESULTS: A total of 40 patients were available for analysis.
      At 14 days, there were no differences in the P2Y(12) reactivity index as assessed
      by vasodilator-stimulated phosphoprotein phosphorylation between treatment groups
      (primary endpoint; p = 0.93). Intra-group comparisons also failed to show any
      differences between baseline and 14-day P2Y(12) reactivity index assessment in
      the placebo and pentoxifylline arms (p = 0.61). There were no significant inter-
      and intra-group differences in all other PD measures. The PD effects did not vary
      according the presence or absence of high on-treatment platelet reactivity.
      CONCLUSIONS: Adjunctive treatment with pentoxifylline is not associated with
      increased platelet inhibitory effects in DM patients with coronary artery disease
      receiving DAPT.

PMID- 21851907
TI  - Recovery of microcirculation after intracoronary infusion of bone marrow
      mononuclear cells or peripheral blood mononuclear cells in patients treated by
      primary percutaneous coronary intervention the Doppler substudy of the Hebe
      trial.
AB  - OBJECTIVES: In the present substudy of the Hebe trial, we investigated the effect
      of intracoronary bone marrow mononuclear cell (BMMC) and peripheral blood
      mononuclear cell (PBMC) therapy on the recovery of microcirculation in patients
      with reperfused ST-segment elevation myocardial infarction (STEMI). BACKGROUND:
      Several studies have suggested that cell therapy enhances neovascularization
      after STEMI. METHODS: Paired Doppler flow measurements were available for 23
      patients in the BMMC group, 18 in the PBMC group, and 19 in the control group.
      Coronary flow was assessed at 3 to 8 days after primary percutaneous coronary
      intervention (PCI) and repeated at 4-month follow-up, with intracoronary Doppler
      flow measurements. RESULTS: At baseline, the coronary flow velocity reserve was
      reduced in the infarct-related artery and improved over 4 months in all 3 groups.
      The increase of coronary flow velocity reserve did not significantly differ
      between the 2 treatment groups and the control group (BMMC group: 2.0 +/- 0.5 to
      3.1 +/- 0.7; PBMC group: 2.2 +/- 0.6 to 3.2 +/- 0.8; control group: 2.0 +/- 0.5
      to 3.4 +/- 0.9). Additionally, the decrease in hyperemic microvascular resistance
      index from baseline to 4-month follow-up was not statistically different between
      the 2 treatment groups and the control group. CONCLUSIONS: In STEMI patients
      treated with primary PCI in the Hebe trial, adjuvant therapy with BMMCs or PBMCs
      does not improve the recovery of microcirculation. Therefore, our data do not
      support the hypothesis of enhanced neovascularization after this mode of cell
      therapy. (Multicenter, randomised trial of intracoronary infusion of autologous
      mononuclear bone marrow cells or peripheral mononuclear blood cells after primary
      percutaneous coronary intervention [PCI]; ISRCTN95796863).

PMID- 21851908
TI  - New insights into the coronary artery bifurcation hypothesis-generating concepts
      utilizing 3-dimensional optical frequency domain imaging.
AB  - Coronary artery bifurcations are a common challenging lesion subset accounting
      for approximately 10% to 20% of all percutaneous coronary interventions. The
      provisional T-stenting approach is generally recommended as the first-line
      management of most lesions. Carina shift is suggested to be the predominant
      mechanism of side-branch pinching during provisional T-stenting and has been
      indirectly inferred from bench work and other intravascular imaging modalities.
      Offline 3-dimensional (3D) reconstructions of patients studied in the first-in
      man trial of the high-frequency (160 frames/s) Terumo optical frequency domain
      imaging system were undertaken using volume-rendering software. Through a series
      of 3D reconstructions, several novel hypothesis-generating concepts are
      presented.

PMID- 21851909
TI  - Noninvasive flow reserve to guide and verify percutaneous coronary intervention.

PMID- 21851910
TI  - Spontaneous aortic thrombosis causing left main coronary occlusion in a man with
      secondary polycythemia.

PMID- 21851911
TI  - Operator experience and radiation exposure during transradial and transfemoral
      procedures.

PMID- 21851913
TI  - Robotic-assisted percutaneous coronary intervention proceed with caution.

PMID- 21851915
TI  - Congratulations to all of you.

PMID- 21851916
TI  - Importance of recognizing pseudo-septal infarction due to electrocardiographic
      lead misplacement.
AB  - Awareness of the problem of false electrocardiographic diagnosis of septal
      infarction due to cranially misplaced precordial leads V1 and V2, a common
      technical error, is important because this pseudo-pathologic finding can trigger
      unnecessary medical procedures and have other adverse sequelae. The non-trivial
      nature of this problem is emphasized by the case of a patient in whom the
      misdiagnosis caused loss of an employment opportunity. We demonstrate how P wave
      morphology in lead V2 can aid the clinician in suspecting erroneous right
      precordial lead placement in cases of apparent septal infarction. Ultimately,
      improved education of health care personnel regarding accurate precordial lead
      positioning technique is needed to minimize the occurrence of this
      electrocardiographic misdiagnosis.

PMID- 21851917
TI  - A low-cost reinforcement procedure improves short-term weight loss outcomes.
AB  - OBJECTIVE: Reinforcement-based treatments, based on behavioral economics models,
      can improve outcomes of medical conditions with behavioral components. This study
      evaluated the efficacy of a low-cost reinforcement intervention to produce
      initial weight loss. METHODS: Overweight individuals (n=56) were randomized to
      one of two 12-week treatments: Lifestyle, Exercise, Attitudes, Relationships,
      Nutrition manual with supportive counseling or that same treatment with
      opportunities to win $1 to $100 prizes for losing weight and completing weight
      loss activities. RESULTS: Patients receiving reinforcement lost significantly
      more weight (6.0% +/- 4.9% baseline bodyweight) than patients in the non
      reinforcement condition (3.5% +/- 4.1%; P=.04). Moreover, 64.3% of patients
      receiving reinforcement achieved weight loss of >= 5% baseline bodyweight versus
      25.0% of those in the non-reinforcement condition (P=.003). Proportional weight
      loss was significantly related to reductions in total cholesterol and 24-hour
      ambulatory heart rate. CONCLUSION: This reinforcement-based intervention
      substantially enhances short-term weight loss, and reductions in weight are
      associated with important changes in clinical biomarkers. Larger-scale evaluation
      of reinforcement-based treatments for weight loss is warranted.

PMID- 21851918
TI  - Individuals reporting idiopathic malodor production: demographics and incidence
      of trimethylaminuria.
AB  - BACKGROUND: Individuals with the metabolic disorder trimethylaminuria may
      sporadically produce malodors despite good hygiene. The psychosocial impact of
      trimethylaminuria can be considerable. However, trimethylaminuria is difficult to
      diagnose without specialized tests, in part because odor production is diet
      dependent, and malodors may not be present during medical examinations. Thus, the
      prevalence and demographics of trimethylaminuria remain unclear. METHODS: We
      tested 353 patients who had unexplained (idiopathic) malodor production for
      trimethylaminuria using a standard choline challenge. We also collected basic
      demographic information. RESULTS: Approximately one third of patients (118)
      tested positive for trimethylaminuria. Consistent with previous reports, women,
      particularly African American women, were significantly overrepresented among
      trimethylaminuria-positive patients. Of note, the same pattern was seen among
      trimethylaminuria-negative patients. Also consistent with previous reports,
      trimethylaminuria-positive women who were still menstruating tended to produce
      higher levels of trimethylamine within +/- 7 days of menses, although this trend
      was statistically marginal (P = .07). CONCLUSION: If our patient sample is
      representative of patients with idiopathic malodor, demographic information (race
      and gender) may not be useful in a differential diagnosis of trimethylaminuria.
      However, undiagnosed cases of trimethylaminuria may be fairly common among
      patients with idiopathic malodor. If so, choline challenge testing should be
      indicated for all such patients because trimethylaminuria is responsive to
      dietary and other treatments. We speculate that testing also might reveal cases
      of trimethylaminuria among those diagnosed with certain psychologic disorders,
      including olfactory reference syndrome.

PMID- 21851919
TI  - Visual acuity after laser in situ keratomileusis to correct high astigmatism in
      adults with meridional amblyopia.
AB  - PURPOSE: To analyze the effect of laser in situ keratomileusis to correct high
      myopic astigmatism in patients with suboptimal best spectacle-corrected visual
      acuity (BSCVA). DESIGN: Retrospective, interventional series of consecutive
      cases. METHODS:  SETTING: Vissum Madrid, Madrid, Spain. PATIENTS: Two hundred
      five eyes of consecutive patients with suboptimal BSCVA and high myopic
      astigmatism of -3 diopters or more. INTERVENTION: Laser in situ keratomileusis
      surgery. MAIN OUTCOME MEASURES: BSCVA. RESULTS: The BSCVA (decimal Snellen
      fraction notation) improved significantly (P = .0001) from a mean preoperative
      0.77 +/- 0.18 (range, 0.05 to 0.90) to 0.81 +/- 0.19 (range, 0.05 to 1.25) 3
      months after surgery. The mean change in lines of BSCVA (decimal Snellen fraction
      notation) was 0.04 +/- 0.11 (range, -0.25 to 0.4). A significant inverse
      relationship (P = .001) was found between the preoperative BSCVA and the
      improvement in BSCVA. CONCLUSIONS: In eyes with high myopic astigmatism and
      suboptimal preoperative BSCVA, laser in situ keratomileusis may result in a
      significant improvement in BSCVA.

PMID- 21851920
TI  - Clinical outcomes of penetrating keratoplasty after autologous cultivated limbal
      epithelial transplantation for ocular surface burns.
AB  - PURPOSE: To report the clinical outcomes of penetrating keratoplasty (PK) after
      autologous cultivated limbal epithelial transplantation in eyes with limbal stem
      cell deficiency (LSCD) after ocular surface burns. DESIGN: Retrospective case
      series. METHODS: This study included 47 patients with unilateral LSCD treated by
      autologous cultivated limbal epithelial transplantation and PK between 2001 and
      2010. PK was performed either along with (single-stage; n = 12) or at least 6
      weeks after (2-stage; n = 35) limbal transplantation. The primary outcome measure
      was corneal allograft survival, and failure was defined clinically as loss of
      central graft clarity. Secondary outcomes were postoperative Snellen visual
      acuity and complications. RESULTS: Most patients were young (mean age, 18 +/-
      11.4 years) males (76.6%) with LSCD resulting from alkali burns (78.7%) and with
      visual acuity less than 20/200 (91.5%). The mean follow-up was 4.2 +/- 1.9 years.
      Kaplan-Meier corneal allograft survival rate at 1 year was significantly greater
      in eyes undergoing 2-stage limbal and corneal transplantation (80 +/- 6%; median
      survival, 4 years) compared with single-stage limbal and corneal transplantation
      (25 +/- 13%; median survival, 6 months; P = .0003). Visual acuity of 20/40 or
      better was attained by 71.4% of eyes with clear corneal grafts. Allograft failure
      occurred in 26 (60.5%) eyes as a result of graft rejection (57.7%), graft
      infiltrate (26.9%), or persistent epithelial defects (15.4%). Recurrence of LSCD
      was more common after single-stage (58.3%) than 2-stage (14.3%) surgery (P =
      .008). CONCLUSIONS: The 2-stage approach of autologous cultivated limbal
      epithelial transplantation followed by PK successfully restores ocular surface
      stability and vision in eyes with chronic ocular burns. The single-stage approach
      is associated with poorer clinical outcomes and should be avoided.

PMID- 21851921
TI  - Survival of mushroom keratoplasty performed in corneas with postinfectious
      vascularized scars.
AB  - PURPOSE: To report the visual outcomes and graft survival rates of mushroom
      keratoplasty for the treatment of postinfectious corneal scars. DESIGN:
      Prospective, noncomparative, interventional case series. METHODS: A microkeratome
      assisted mushroom-shaped keratoplasty was performed in 31 eyes of 31 patients
      with a central vascularized full-thickness leukoma, resulting from infectious
      keratitis of various origin (herpes simplex virus, n = 16; bacteria, n = 10;
      Acanthamoeba, n = 5), with healthy endothelium. The donor graft consisted of a
      large anterior stromal lamella (9.0 mm in diameter and +/- 250 MUm in thickness)
      and a small posterior button (5 to 6 mm in diameter). Visual acuity, refraction,
      and endothelial cell density were evaluated before surgery, as well as at 12, 24,
      and 36 months after surgery, and the postoperative graft survival rate was
      evaluated. RESULTS: Three years after surgery, in 26 (83.8%) of 31 patients, best
      spectacle-corrected visual acuity was 20/40 or better with a refractive
      astigmatism of 4.5 diopters or less. The endothelial cell count at the last
      follow-up examination averaged 1584 +/- 381 cells/mm(2), with an average cell
      loss of 40.7% from the preoperative value. The survival rate at 3 years was
      90.3%, improving to 96.7% when excluding nonimmunologic causes for graft failure.
      CONCLUSIONS: Similarly to penetrating keratoplasty, microkeratome-assisted
      mushroom keratoplasty restores vision in eyes with postinfectious, full
      thickness, central corneal scars. For these vascularized corneas at high risk for
      immunologic rejection, mushroom keratoplasty combines the visual and refractive
      advantages of large penetrating keratoplasty grafts with the high survival rate
      of small penetrating keratoplasty grafts.

PMID- 21851922
TI  - Retinal and choroidal thickness in early age-related macular degeneration.
AB  - PURPOSE: To compare retinal thickness and choroidal thickness at increasing
      retinal eccentricity in individuals with early age-related macular degeneration
      (AMD) and in healthy controls using enhanced choroidal penetration, 3-dimensional
      optical coherence tomography at 1060 nm. DESIGN: Cross-sectional study. METHODS:
      Individuals with early AMD (n = 16; mean age, 71.6 +/- 8.5 years) and a
      comparison group of healthy controls (n = 16; 67.6 +/- 5.4 years) were recruited.
      Three-dimensional (20 degrees * 20 degrees) long-wavelength optical coherence
      tomography (1060 nm) images (approximately 8-MUm axial resolution; 47,000 A
      scans/second, centered on the fovea) were obtained from all participants after
      pupil dilation. Retinal thickness was measured between the inner limiting
      membrane and the retinal pigment epithelium. Choroidal thickness was measured
      between the retinal pigment epithelium and the choroid-scleral interface.
      Thickness measurements were obtained subfoveally and at 0.5-mm intervals to a
      maximum of 2.0 mm nasally, temporally, superiorly, and inferiorly. The main
      outcome measures were retinal and choroidal thickness (measured in micrometers)
      at different eccentricities on vertical and horizontal meridians. RESULTS: Mean
      retinal thickness was reduced significantly in the group of participants with
      early AMD compared with the control group at multiple locations within 2.0 mm of
      the fovea. This difference was most significant at the fovea, where the mean
      retinal thickness of the early AMD group was 179 +/- 27 MUm and that of the
      control group was 202 +/- 18 MUm (P = .008). There was no significant difference
      in choroidal thickness between groups at any location. CONCLUSIONS: Retinal
      thickness is reduced in early AMD, but choroidal thickness seems to be unaffected
      by the early disease process.

PMID- 21851923
TI  - Correlation between ficolin-3 and vascular endothelial growth factor-to-pigment
      epithelium-derived factor ratio in the vitreous of eyes with proliferative
      diabetic retinopathy.
AB  - PURPOSE: To investigate the relationship of ficolin-3 with inflammatory and
      angiogenic factors, namely, vascular endothelial growth factor (VEGF) and pigment
      epithelium-derived factor (PEDF), in the vitreous of eyes with proliferative
      diabetic retinopathy (PDR). DESIGN: Case-control study. METHODS: Vitreous fluid
      and serum samples were obtained at the time of vitreoretinal surgery from 21 eyes
      of 21 patients with PDR and from 16 eyes of 16 nondiabetic patients with
      idiopathic macular hole. Ficolin-3, VEGF, and PEDF concentrations were determined
      by enzyme-linked immunosorbent assay. RESULTS: Vitreous ficolin-3 levels were
      significantly higher in eyes with PDR than in eyes with idiopathic macular hole.
      Similarly, VEGF levels also were significantly higher in eyes with PDR than in
      eyes with idiopathic macular hole. In contrast, vitreous PEDF concentrations were
      significantly lower in eyes with PDR than in eyes with idiopathic macular hole,
      and the VEGF-to-PEDF ratio was higher in eyes with PDR than in eyes with
      idiopathic macular hole. Furthermore, a significant correlation between ficolin-3
      and the VEGF-to-PEDF ratio was observed in the vitreous of eyes with PDR. In
      addition, serum ficolin-3 levels in eyes with PDR were higher than the levels in
      eyes with idiopathic macular hole, and the vitreous ficolin-3 levels also
      correlated with serum ficolin-3 levels. CONCLUSIONS: We found that ficolin-3
      levels were elevated in the vitreous fluid of patients with PDR. Our results
      suggest that ficolin-3 may be used as a new therapeutic target for treatment of
      PDR.

PMID- 21851925
TI  - Work-related upper quadrant musculoskeletal disorders in midwives, nurses and
      physicians: A systematic review of risk factors and functional consequences.
AB  - BACKGROUND: Given a worldwide shortage of primary health care workers predicted
      to worsen, it is vital to address sources of attrition among these professionals.
      One such source may be work-related musculoskeletal disorders. We aimed to
      identify risk factors for and functional consequences of work-related upper
      quadrant musculoskeletal disorders in midwives, nurses and physicians. METHODS:
      Eighteen of 87 studies identified from an electronic database search met the
      inclusion and quality criteria. RESULTS: Job demands, demanding work schedules
      and physical exposures have the strongest associations with work-related upper
      quadrant musculoskeletal disorders. Functional consequences included widespread
      use of prescription and over-the-counter medications and major negative impact on
      activities of daily living. No studies of midwives were located. CONCLUSION: High
      quality studies of midwives as well as better-designed prospective studies of
      nurses and physicians are needed. Results of such studies could inform preventive
      strategies and reduce the contribution of work-related musculoskeletal disorders
      to attrition.

PMID- 21851924
TI  - The association between glaucomatous and other causes of optic neuropathy and
      sleep apnea.
AB  - PURPOSE: To determine whether an association exists between sleep apnea and open
      angle glaucoma, normal-tension glaucoma, nonarteritic ischemic optic neuropathy
      (NAION), papilledema, or idiopathic intracranial hypertension (IIH) and whether
      treatment with continuous positive airway pressure affects the development of
      these conditions. DESIGN: Retrospective, longitudinal cohort study. METHODS:
      Billing records for beneficiaries 40 years of age and older enrolled in a large
      United States managed care network from 2001 through 2007 were reviewed.
      Incidence of open-angle glaucoma, normal-tension glaucoma, NAION, papilledema,
      and IIH were determined for the beneficiaries and were stratified by sleep apnea
      status. Cox regression analyses determined the hazard of each of these conditions
      developing among individuals with and without sleep apnea, with adjustment for
      sociodemographic, ocular, and medical conditions. RESULTS: Among the 2 259 061
      individuals in the study, 156 336 (6.9%) had 1 or more sleep apnea diagnoses. The
      hazard of open-angle glaucoma was no different among persons with sleep apnea
      either treated (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI],
      0.82 to 1.18) or untreated with continuous positive airway pressure (HR, 1.01;
      95% CI, 0.98 to 1.05) and individuals without sleep apnea. Similar findings were
      observed when assessing the hazard of normal-tension glaucoma developing (P > .05
      for both comparisons). A significantly increased hazard of NAION developing (HR,
      1.16; 95% CI, 1.01 to 1.33) and IIH (HR, 2.03; 95% CI, 1.65 to 2.49) was observed
      among individuals with sleep apnea who were not receiving continuous positive
      airway pressure therapy as compared with individuals without sleep apnea,
      although similar increased risks could not be demonstrated among continuous
      positive airway pressure-treated sleep apnea patients for these conditions (P >
      .05 for both comparisons). CONCLUSIONS: Patients with untreated sleep apnea are
      at increased risk for IIH and NAION. Clinicians should consider appropriate
      screening for these conditions in sleep apnea patients.

PMID- 21851926
TI  - Dental pulp cells derived from permanent teeth express higher levels of R
      cadherin than do deciduous teeth: implications of the correlation between R
      cadherin expression and restriction of multipotency in mesenchymal stem cells.
AB  - OBJECTIVES: The aim of this study was to characterize the expression status of
      cadherins in dental pulp-derived mesenchymal progenitor/stem cells from deciduous
      and permanent teeth, and to determine how cadherins affect the multipotency of
      the progenitor/stem cells. MATERIALS AND METHODS: We evaluated and compared the
      expression status of cadherins in dental pulp-derived cells from deciduous teeth
      and in cells from permanent teeth by using an array of primers for amplification
      of RNA encoding human cell adhesion molecules and a real time PCR system. In
      order to elucidate how cadherins (which are differentially expressed in deciduous
      and permanent teeth) affect the multipotency of the dental pulp-derived
      progenitor/stem cells, the ability of the dental pulp cells to differentiate into
      adipocytes and osteoblasts was evaluated. RESULTS: R-cadherin was found to be
      vigorously expressed in the dental pulp cells derived from permanent teeth but
      not in the dental pulp cells derived from deciduous teeth. N-cadherin was found
      to be expressed essentially equally in both types of cells. The ability of the
      dental pulp cells of deciduous teeth to differentiate into adipocytes and
      osteoblasts was found to be much higher than that of cells obtained from
      permanent teeth. CONCLUSION: R-cadherin may be a key molecule for providing
      control over the multipotency of the dental pulp-derived mesenchymal stem cells.

PMID- 21851927
TI  - Psychometric properties of the community integration questionnaire in a
      heterogeneous sample of adults with physical disability.
AB  - OBJECTIVE: To investigate the psychometric properties of the Community
      Integration Questionnaire (CIQ) in a mixed sample of adults with physical
      disabilities. DESIGN: Cross-sectional, survey study. SETTING: Academic and
      community medical clinics, national registry, and self-referral. PARTICIPANTS:
      Community-dwelling adults with spinal cord injury (n=146), multiple sclerosis
      (n=174), limb loss (n=158), or muscular dystrophy (n=273). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: CIQ, General Health item from the Medical
      Outcomes Study 36-Item Short-Form Health Survey, and Mental Health Scale from the
      Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Based on the
      original scoring procedures, the CIQ Total scale and Home Integration subscale
      demonstrated acceptable internal consistency; however, reliability indices for
      the Social Integration and Productive Activities subscales were suboptimal. The
      exploratory factor analysis yielded a 4-factor solution (accounting for
      approximately 63% of the variance) that did not replicate the original factor
      structure of the CIQ. The results of the confirmatory factor analyses indicated
      that a modified 3-factor solution provided the best fit to the data from our
      samples. Using a revised scoring system based on these findings, the CIQ
      demonstrated improved reliability relative to the original scoring and good
      concurrent validity. CONCLUSIONS: The results provide general support for the
      validity of the CIQ as a measure of participation in adults with physical
      disabilities. However, our results indicate that some small modifications to the
      original scoring system are needed to optimize its use in this patient group.
      Additional research is needed to refine the measurement of participation in these
      and other populations.

PMID- 21851928
TI  - Association of disability duration with physical therapy services provided after
      meniscal surgery in a workers' compensation population.
AB  - OBJECTIVE: To examine the association between physical therapy (PT) amount and
      type (eg, active exercise and passive modalities) received postmeniscectomy with
      subsequent days of work disability. DESIGN: Historical prospective study.
      SETTING: Workers' compensation administrative claims data source. PARTICIPANTS:
      Patients (N=3888) with a new knee injury filed between January 1, 2001, and
      December 31, 2003, who underwent meniscectomy within 6 months postinjury.
      INTERVENTIONS: PT services received within 42 days postmeniscectomy. Patients
      were divided into 9 groups based on PT service amount and type received during
      the exposure period (no PT, only low active, only high active, only low passive,
      only high passive, low active/low passive, high active/low passive, low
      active/high passive, high active/high passive). MAIN OUTCOME MEASURE: Number of
      disability days post-exposure period and truncated at the end of the 1.5-year
      outcome period based on lost-time payments. RESULTS: During the exposure period,
      32.5% received no PT services, 15.3% had only active, 1.5% had only passive, and
      50.8% had a combination of both. After controlling for covariates (including
      severity indicators and physical job demands), receipt of any passive services
      was associated significantly with a greater number of disability days, and no
      significant differences were found for those who received only active PT compared
      with those receiving no PT. Severity indicators, including opioid use pre- and
      postsurgery, more disability before surgery, and greater surgery severity, were
      associated with more disability days, whereas physical job demands were not.
      CONCLUSIONS: Our results suggest that passive PT services provided
      postmeniscectomy may be counterproductive to work resumption. In addition,
      disability duration was shorter or no different for those who received no PT
      services than for those who received any type of PT services. With better control
      of confounders in future studies, a beneficial effect of active PT might be
      found. For the development of rehabilitation guidelines, randomized controlled
      trials are needed to better understand the effectiveness of active and passive PT
      services postmeniscectomy.

PMID- 21851929
TI  - Cost-effectiveness of Internet-based cognitive behavior therapy vs. cognitive
      behavioral group therapy for social anxiety disorder: results from a randomized
      controlled trial.
AB  - Social anxiety disorder (SAD) is highly prevalent and associated with a
      substantial societal economic burden, primarily due to high costs of productivity
      loss. Cognitive behavior group therapy (CBGT) is an effective treatment for SAD
      and the most established in clinical practice. Internet-based cognitive behavior
      therapy (ICBT) has demonstrated efficacy in several trials in recent years. No
      study has however investigated the cost-effectiveness of ICBT compared to CBGT
      from a societal perspective, i.e. an analysis where both direct and indirect
      costs are included. The aim of the present study was to investigate the cost
      effectiveness of ICBT compared to CBGT from a societal perspective using a
      prospective design. We conducted a randomized controlled trial where participants
      with SAD were randomized to ICBT (n=64) or CBGT (n=62). Economic data were
      assessed at pre-treatment, immediately following treatment and six months after
      treatment. Results showed that the gross total costs were significantly reduced
      at six-month follow-up, compared to pre-treatment in both treatment conditions.
      As both treatments were equivalent in reducing social anxiety and gross total
      costs, ICBT was more cost-effective due to lower intervention costs. We conclude
      that ICBT can be more cost-effective than CBGT in the treatment of SAD and that
      both treatments reduce societal costs for SAD.

PMID- 21851930
TI  - WITHDRAWN: Pax genes during neural development and their potential role in
      neuroregeneration.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21851931
TI  - Studies on the synthesis of Lewis-y oligosaccharides.
AB  - Lewis-y histo-blood group oligosaccharides are tumour-associated antigens
      prevalent in several different types of cancer, and they may also be secondary
      ligands for bacterial toxins from Escherichia coli and Vibrio cholerae. The key
      step in the synthesis of these sterically congested oligosaccharides involves
      difucosylation of partially protected lactosamine derivatives. Existing methods
      require either prolonged reaction times or elaborate glycosyl donors to ensure
      high stereoselectivity. Herein we report an optimised procedure for using a
      simple thioglycoside donor that leads to the desired products in high yield and
      excellent stereoselectivity. It is found that initial glycosylation of the 3'
      hydroxy group of lactosamine derivatives in dichloromethane solution can inhibit
      subsequent glycosylation at the 2-position; however, reaction in toluene solution
      leads to Lewis-y oligosaccharides in high yield.

PMID- 21851932
TI  - Imaging features, follow-up, and management of incidentally detected renal
      lesions.
AB  - Incidental renal masses are common findings on cross-sectional imaging. Most will
      be readily identified as simple cysts, but with an inexorable rise in abdominal
      imaging, [particularly computed tomography (CT)], coupled with a rise in the
      incidence of renal cancer, the likelihood of detecting a malignant mass is
      increasing. This review informs the radiologist which lesions can be safely
      ignored, which will require further imaging for accurate categorization, and
      which require referral for consideration of treatment. For the small proportion
      of lesions that are indeterminate, careful attention to imaging technique, and
      the use of unenhanced and contrast-enhanced CT or magnetic resonance imaging
      (MRI) in all but a few specific instances will accurately characterize such
      lesions. The figures have been chosen to illustrate specific imaging features of
      common renal lesions. Management options for malignant, or presumed malignant,
      renal masses include active surveillance, percutaneous ablation, laparoscopic or
      open, partial or total nephrectomy. Biopsy has a role in determining the nature
      of masses that remain indeterminate on cross-sectional imaging, prior to
      definitive treatment. Common pitfalls in assessing incidental renal lesions are
      emphasized; some of these are due to sub-optimal imaging techniques and others to
      errors in interpretation.

PMID- 21851934
TI  - Sedentary nestlings of Wood Stork as monitors of mercury contamination in the
      gold mining region of the Brazilian Pantanal.
AB  - Sedentary organisms that are at top trophic levels allow inference about the
      level of local mercury contamination. We evaluated mercury contamination in
      feather tissue of nestling Wood Storks (Mycteria americana), sampled in different
      parts of the Brazilian Pantanal that were variably polluted by mercury releases
      from gold mining activities. Levels of mercury in feathers sampled in seven
      breeding colonies were determined by atomic absorption spectroscopy, and the mean
      value of mercury concentration was 0.557 MUg/g, dry weight (n=124), range 0.024
      4.423 MUg/g. From this total sample, 21 feathers that represent 30% of nestlings
      collected in Porto da Fazenda and Tucum colonies, in the northern region, ranged
      from 1.0 to 4.43 MUg/g, dry weight (median value=1.87 MUg/g). We found
      significant differences among regions (H=57.342; p=0<0.05). Results suggest that
      permanently flooded areas, or along mainstream rivers are more contaminated by
      mercury than dry areas, regardless of the distance from the gold mining center,
      which is located in the northern Pantanal. Highest values found in nestlings
      feathers were similar to those found in feathers of adult birds and in tissues of
      adult mammals that are less sedentary and were captured in the same region of
      Pantanal. These findings indicate that mercury released has been biomagnified and
      it is present in high concentrations in tissues of top consumers. We suggest a
      program to monitor mercury availability in this ecosystem using sedentary life
      forms of top predators like Wood Storks or other piscivorous birds.

PMID- 21851933
TI  - Anatomic and electro-physiologic connectivity of the language system: a combined
      DTI-CCEP study.
AB  - Here we present a novel multimodal analysis of network connectivity in the
      language system. We assessed connectivity of Broca's area using tractography with
      diffusion tensor imaging (DTI), and with cortico-cortical evoked potentials
      (CCEPs) to measure the spread of artificial currents applied directly to human
      cortex. We found that both the amplitude and latency of CCEP currents
      significantly correlates (r(2)=0.41, p<10(-16)) with the number of DTI pathways
      connecting the stimulation and recording loci. This strategy of relating
      electrical information flow with the neural architecture will likely yield new
      insights into cognitive processes.

PMID- 21851935
TI  - Fishing, fish consumption and advisory awareness among Louisiana's recreational
      fishers.
AB  - This paper presents results from the first known population-based survey of
      recreational fishers in Louisiana (n=1774). The ultimate goal of this study was
      to obtain data in support of the development of regional advisories for a high
      exposure population with unique seafood consumption patterns. Between July and
      August of 2008, a survey was mailed to a random sample of licensed recreational
      fishers to characterize local fishing habits, sportfish consumption, and advisory
      awareness. Eighty-eight percent of respondents reported eating sportfish.
      Respondents ate an estimated mean of four fish meals per month, of which,
      approximately half were sportfish. Over half of all sportfish meals (54%) were
      caught in the Gulf of Mexico or bordering brackish areas. Sportfish consumption
      varied by license and gender; and was highest among Sportsman's Paradise license
      holders (2.8+/-0.2 meals per month), and males (2.2+/-0.1 meals per month). The
      most frequently consumed sportfish species were red drum, speckled trout,
      catfish, bass, crappie and bream. Advisory awareness rates varied by gender,
      ethnicity, geographic area, license type, age and education; and were lowest
      among women (53%), African-Americans (43%), fishers from the southeast of
      Louisiana (50%), holders of Senior Hunting and Fishing licenses (51%),
      individuals between 15 and 19 years of age (41%), and individuals with less than
      a high school education (43%). Results were used to identify ways to optimize
      monitoring, advisory development and outreach activities.

PMID- 21851936
TI  - Self-correction in tripronucleated human embryos.
AB  - OBJECTIVE: To explore the occurrence of ploidy and parental self-correction in
      tripronuclear (TPN) human embryos. DESIGN: Experimental. SETTING: Research
      facility. PATIENT(S): Thirty-two TPN embryos resulting from intracytoplasmic
      sperm injection (ICSI-TPN) and 18 TPN embryos resulting from conventional IVF
      (IVF-TPN). INTERVENTION(S): Tripronuclear embryos were cultured in vitro for 6
      days. Those with >= 6 cells were biopsied for ploidy analysis. Blastocysts were
      studied for ploidy or parental inheritance. Heteroparental inheritance was
      determined after comparing polymorphic loci in the genomic DNA of a blastocyst
      and in the parents' DNA. MAIN OUTCOME MEASURE(S): Tripronuclear origin, cell
      number at biopsy, chromosome analysis using fluorescent in situ hybridization,
      parental inheritance analysis using polymerase chain reaction amplification and
      sequencing, in vitro development to the blastocyst stage, and percentage of
      diploid and triploid cleavage embryos and blastocysts. RESULT(S): Half of ICSI
      TPN embryos became self-corrected blastocysts whereas only one IVF-TPN embryo
      did. CONCLUSION(S): Both ICSI-TPN and IVF-TPN embryos are capable of self
      correction, but the latter to a lesser extent. Neither parental inheritance nor
      ploidy determines the ability of a TPN embryo to progress to the blastocyst
      stage. However, the ability of a TPN embryo to become self-corrected is
      determined by the parental origin of the extra pronucleus.

PMID- 21851937
TI  - De novo exceptional complex chromosomal rearrangement in a healthy fertile male:
      case report and review of the literature.
AB  - OBJECTIVE: To report a de novo exceptional complex chromosomal rearrangement
      (CCR) with four breakpoints in the male partner of a couple with recurrent
      abortions. DESIGN: Case report and review of the literature. SETTING: Genetics
      laboratory in a private hospital. PATIENT(S): A couple referred for recurrent
      abortions. INTERVENTION(S): Cytogenetic and sperm fluorescence in situ
      hybridization (FISH) techniques. MAIN OUTCOME MEASURE(S): Karyotype and FISH
      sperm results. RESULT(S): The couple was phenotypically normal, with no family
      history of miscarriage or infertility. Female karyotype was normal. Male
      karyotype followed by FISH analysis showed a de novo CCR with four breakpoints:
      t(5,13,16)(q11.1, q14.3, q12.2), ins(16;13)(q12.2;q?q14.2). ish
      t(5;13;16)(wcp5+,wcp13+), ins(16;13)(wcp13+). CONCLUSION(S): Exceptional de novo
      CCR male carriers with recurrent abortions are extremely rare. Patients with CCRs
      have limited options to achieve a normal pregnancy. Careful consideration and
      assessment should be provided upon counseling of couples with CCRs.

PMID- 21851938
TI  - Multinucleation of a sibling blastomere on day 2 suggests unsuitability for
      embryo transfer in IVF-preimplantation genetic screening cycles.
AB  - OBJECTIVE: To evaluate the impact of multinucleation of a sibling blastomere of
      day 2 embryos on the rate of aneuploidy detected by day 3 preimplantation genetic
      screening (PGS) biopsy and the effect on subsequent implantation and pregnancy
      rates. DESIGN: Retrospective cohort study. SETTING: University-based IVF center.
      PATIENT(S): A total of 141 couples undergoing their first IVF-PGS cycle for
      idiopathic recurrent pregnancy loss (RPL) or multiple failed IVF implantations.
      INTERVENTION(S): Biopsy of single-nucleated blastomeres for PGS analysis of
      chromosomes X, Y, 13, 15, 16, 17, 18, 21, and 22 by fluorescence in situ
      hybridization. MAIN OUTCOME MEASURE(S): Aneuploidy, implantation, and pregnancy
      rates. RESULT(S): PGS revealed an increased incidence of aneuploidy when
      comparing multinucleated day 2 embryos with single-nucleated embryos (85% vs.
      78%; relative risk 0.92 (95% confidence interval 0.84-1.00). Transfer of single
      nucleated euploid embryos resulted in clinical pregnancy and implantation rates
      of 28% and 24%. Transfer of multinucleated euploid embryos resulted in no
      implantations. CONCLUSION(S): The presence of multinucleated blastomeres on day 2
      of embryo development, 1 day before biopsy, predicts an increase of aneuploidy
      and poor pregnancy outcomes in IVF-PGS cycles.

PMID- 21851939
TI  - Clomiphene citrate versus letrozole: molecular analysis of the endometrium in
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: To compare the effect of clomiphene citrate (CC) and letrozole on
      endometrial receptivity in women with polycystic ovary syndrome (PCOS). DESIGN: A
      randomized controlled trial. SETTING: University teaching hospital. PATIENT(S):
      Ten anovulatory women with PCOS and 5 fertile ovulatory women. INTERVENTION(S):
      Patients received 2.5 mg of letrozole on cycle days 3-7 (5 patients, 1 cycle) or
      50 mg of CC on cycle days 5-9 (5 patients, 1 cycle). MAIN OUTCOME MEASURE(S):
      Serum estrogen (E) and progesterone (P) endometrial protein and messenger RNA
      (mRNA) expression of leukemia inhibitory factor (LIF), dickkhopf homolog 1 (DKK
      1), fibroblast growth factor 22 (FGF-22), and endometrial mRNA expression of
      LIF/GP130 receptor (LIFR). RESULT(S): No statistically significant differences
      were observed between groups compared with fertile ovulatory women when serum E
      and P were examined, or between body mass index (BMI), and cycle day at time of
      biopsy. Letrozole increased mRNA expression of LIF, DKK1, LIFR, and FGF-22,
      whereas CC only increased endometrial mRNA expression of LIF. Letrozole mRNA
      expression directly translated into increased protein expression of like genes in
      the endometrium. The CC protein expression of DKK-1 was significantly decreased
      compared with controls. CONCLUSION(S): Letrozole positively influences a number
      of markers of endometrial receptivity compared with CC.

PMID- 21851941
TI  - An Arabic version of the perceived stress scale: translation and validation
      study.
AB  - BACKGROUND: The Perceived Stress Scale has been designed to measure the degree to
      which situations in a person's life are perceived as stressful. OBJECTIVE: The
      paper describes the development of an Arabic version of the Perceived Stress
      Scale. DESIGN: A translation process with cross-cultural considerations was
      employed to produce an Arabic version of the Perceived Stress Scale. SETTINGS:
      Participants were asked to complete the Arabic version Perceived Stress Scale
      twice in their homes. PARTICIPANTS: The Jordanian study population for the Arabic
      version Perceived Stress Scale validation consisted of 126 volunteers (74 male,
      52 female). Ninety participants completed the scale twice (55 male, 35 female),
      of whom 58 were high schools teachers and 32 technical workers. Arabic was the
      first language of all participants and all gave informed consent. RESULTS: The
      Arabic version Perceived Stress Scale reliability and validity were evaluated.
      Prior to an exploratory factor analysis, the suitability of data for factor
      analysis was assessed with acceptable results. The exploratory factor analysis
      showed two factors with eigenvalues greater than 1.0 (45.0% of variance). The
      Cronbach's alpha coefficients were 0.74 (Factor 1), 0.77 (Factor 2) and 0.80 for
      the Arabic version Perceived Stress Scale overall. The test-retest reliability
      had an intra-correlation coefficient of 0.90. CONCLUSIONS: The Arabic version
      Perceived Stress Scale showed an adequate reliability and validity. Therefore,
      the Arabic Perceived Stress Scale is considered a suitable instrument to assess
      perceived stress in Arabic people.

PMID- 21851940
TI  - Cross-cultural adaptation of the Dutch Short Musculoskeletal Function Assessment
      questionnaire (SMFA-NL): internal consistency, validity, repeatability and
      responsiveness.
AB  - The purpose of this study was to translate and culturally adapt the Dutch version
      of the Short Musculoskeletal Function Assessment questionnaire (SMFA-NL) and to
      investigate the internal consistency, validity, repeatability and responsiveness
      of the translated version. The original SMFA was first translated and culturally
      adapted from English into Dutch according to a standardised procedure and
      subsequently tested for clinimetric quality. The study population consisted of
      162 patients treated for various musculoskeletal injuries or disorders at the
      departments of Orthopedics and Traumatology. All respondents filled in the SMFA
      NL and the SF-36 and a region-specific questionnaire. To determine repeatability,
      87 respondents filled in the SMFA-NL for a second time after a time interval of
      three to four weeks. To determine responsiveness, 29 respondents who were treated
      for their injury within three months before the first assessment filled in the
      SMFA-NL for a second time after two to three months. The following analyses were
      performed to evaluate clinimetric quality of the SMFA-NL: factor analysis and
      Cronbach's alpha (internal consistency), floor and ceiling effects, Spearman's
      Rho (construct validity), intraclass correlation coefficients and the Bland &
      Altman method (repeatability), and standardised response means (SRM)
      (responsiveness). Factor analysis demonstrated four subscales of the SMFA-NL.
      Both the newly identified subscales of the SMFA-NL and the conventional subscales
      of the SMFA showed good internal consistency. No floor and some ceiling effects
      were found. Construct validity was good, as high correlations were found between
      the subscales of the SMFA-NL and the respective subscales of the SF-36 and the
      region-specific questionnaires. Repeatability of the SMFA-NL subscales was high,
      with no systematic bias between first and second assessment. Responsiveness of
      the SMFA-NL was moderate, as small to moderate SRMs were found. We successfully
      translated and culturally adapted a Dutch version of the Short Musculoskeletal
      Function Assessment questionnaire (SFMA-NL). This study shows that the SMFA-NL is
      a valid, reliable and moderately responsive method for the assessment of
      functional status of patients who have a broad range of musculoskeletal
      disorders. Furthermore, it will allow for comparison between different patient
      groups as well as for cross-cultural comparisons.

PMID- 21851942
TI  - Differences in the mode of presentation for acute coronary syndrome by pre
      hospitalization medication, in relation to coronary risk factors, East-Osaka
      acute coronary syndrome (EACS) registry.
AB  - BACKGROUND: Pre-hospitalization medication such as aspirin and nitrates has been
      shown to affect the mode of presentation in acute coronary syndrome (ACS).
      However, it is not formally assessed whether other cardiovascular medications may
      be contributed to the differences in the mode of presentation, especially in
      relation to coronary risk factors. METHODS AND RESULTS: We conducted a
      registration study of patients (M/F 850/323) with either ST-segment elevation
      myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction
      (NSTEMI) or unstable angina (UA), and examined the differences in the mode of
      presentation, pre-hospitalization medication, and coronary risk factors. The
      ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in
      patients having pre-hospitalization medication with aspirin, nitrates or statins,
      but not with other medications such as beta-blockers in multivariate analysis.
      Pre-hospitalization medication with aspirin and nitrates was significantly
      associated with the same reduction of the ratio in patients with male gender,
      hypertension, diabetes mellitus and a history of coronary artery disease.
      However, in patients who smoked, were obese and hypercholesterolemic, pre
      hospitalization medication with nitrates was significantly associated with the
      reduced ratio. The ratio was significantly low in patients with males and
      hypercholesterolemia treated with statins before admission. CONCLUSION: Depending
      on their coronary risk factors, pre-hospitalization medication with aspirin,
      nitrates or statins was associated with a different presentation and evolution of
      ACS.

PMID- 21851943
TI  - Evolving biaxial mechanical properties of mouse carotid arteries in hypertension.
AB  - Quantifying the time course of load-induced changes in arterial wall geometry,
      microstructure, and properties is fundamental to developing mathematical models
      of growth and remodeling. Arteries adapt to altered pressure and flow by
      modifying wall thickness, inner diameter, and axial length via marked cell and
      matrix turnover. To estimate particular biomaterial implications of such
      adaptations, we used a 4-fiber family constitutive relation to quantify passive
      biaxial mechanical behaviors of mouse carotid arteries 0 (control), 7-10, 10-14,
      or 35-56 days after an aortic arch banding surgery that increased pulse pressure
      and pulsatile flow in the right carotid artery. In vivo circumferential and axial
      stretches at mean arterial pressure were, for example, 11% and 26% lower,
      respectively, in hypertensive carotids 35-56 days after banding than in
      normotensive controls; this finding is consistent with observations that
      hypertension decreases distensibility. Interestingly, the strain energy W stored
      in the carotids at individual in vivo conditions was also less in hypertensive
      compared with normotensive carotids. For example, at 35-56 days after banding, W
      was 24%, 39%, and 47% of normal values at diastolic, mean, and systolic
      pressures, respectively. The energy stored during the cardiac cycle, W(sys)
      W(dias), also tended to be less, but this reduction did not reach significance.
      When computed at normal in vivo values of biaxial stretch, however, W was well
      above normal for the hypertensive carotids. This net increase resulted from an
      overall increase in the collagen-related anisotropic contribution to W despite a
      decrease in the elastin-related isotropic contribution. The latter was consistent
      with observed decreases in the mass fraction of elastin.

PMID- 21851944
TI  - Ambulatory measurement of ankle kinetics for clinical applications.
AB  - This study aimed to design and validate the measurement of ankle kinetics (force,
      moment, and power) during consecutive gait cycles and in the field using an
      ambulatory system. An ambulatory system consisting of plantar pressure insole and
      inertial sensors (3D gyroscopes and 3D accelerometers) on foot and shank was
      used. To test this system, 12 patients and 10 healthy elderly subjects wore shoes
      embedding this system and walked many times across a gait lab including a force
      plate surrounded by seven cameras considered as the reference system. Then, the
      participants walked two 50-meter trials where only the ambulatory system was
      used. Ankle force components and sagittal moment of ankle measured by ambulatory
      system showed correlation coefficient (R) and normalized RMS error (NRMSE) of
      more than 0.94 and less than 13% in comparison with the references system for
      both patients and healthy subjects. Transverse moment of ankle and ankle power
      showed R>0.85 and NRMSE<23%. These parameters also showed high repeatability
      (CMC>0.7). In contrast, the ankle coronal moment of ankle demonstrated high error
      and lower repeatability. Except for ankle coronal moment, the kinetic features
      obtained by the ambulatory system could distinguish the patients with ankle
      osteoarthritis from healthy subjects when measured in 50-meter trials. The
      proposed ambulatory system can be easily accessible in most clinics and could
      assess main ankle kinetics quantities with acceptable error and repeatability for
      clinical evaluations. This system is therefore suggested for field measurement in
      clinical applications.

PMID- 21851945
TI  - Standard operation protocol for analysis of lipid hydroperoxides in human serum
      using a fully automated method based on solid-phase extraction and liquid
      chromatography-mass spectrometry in selected reaction monitoring.
AB  - Standard operating procedures (SOPs) are of paramount importance in the
      analytical field to ensure the reproducibility of the results obtained among
      laboratories. SOPs gain special interest when the aim is the analysis of
      potentially unstable compounds. An SOP for analysis of lipid hydroperoxides
      (HpETEs) is here reported after optimization of the critical steps to be
      considered in their analysis in human serum from sampling to final analysis. The
      method is based on automated hyphenation between solid-phase extraction (SPE) and
      liquid chromatography-mass spectrometry (LC-MS). The developed research involves:
      (i) optimization of the SPE and LC-MS steps with a proper synchronization; (ii)
      validation of the method-viz. accuracy study (estimated as 86.4% as minimum
      value), evaluation of sensitivity and precision, which ranged from 2.5 to 7.0
      ng/mL (0.25-0.70 ng on column) as quantification limit and precision below
      13.2%), and robustness study (reusability of the cartridge for 5 times without
      affecting the accuracy and precision of the method); (iii) stability study,
      involving freeze-thaw stability, short-term and long-term stability and stock
      solution stability tests. The results thus obtained allow minimizing both random
      and systematic variation of the metabolic profiles of the target compounds by
      correct application of the established protocol.

PMID- 21851946
TI  - Experimental designs for modeling retention patterns and separation efficiency in
      analysis of fatty acid methyl esters by gas chromatography-mass spectrometry.
AB  - The retention behavior of components analyzed by chromatography varies with
      instrumental settings. Being able to predict how changes in these settings alter
      the elution pattern is useful, both with regards to component identification, as
      well as with regards to optimization of the chromatographic system. In this work,
      it is shown how experimental designs can be used for this purpose. Different
      experimental designs for response surface modeling of the separation of fatty
      acid methyl esters (FAME) as function of chromatographic conditions in GC have
      been evaluated. Full factorial, central composite, Doehlert and Box-Behnken
      designs were applied. A mixture of 38 FAMEs was separated on a polar cyanopropyl
      substituted polysilphenylene-siloxane phase capillary column. The temperature
      gradient, the start temperature of the gradient, and the carrier gas velocity
      were varied in the experiments. The modeled responses, as functions of
      chromatographic conditions, were retention time, retention indices, peak widths,
      separation efficiency and resolution between selected peak pairs. The designs
      that allowed inclusion of quadratic terms among the predictors performed
      significantly better than factorial design. Box-Behnken design provided the best
      results for prediction of retention, but the differences between the central
      composite, Doehlert and Box-Behnken designs were small. Retention indices could
      be modeled with much better accuracy than retention times. However, because the
      errors of predicted tR of closely eluting peaks were highly correlated, models of
      resolution (Rs) that were based on retention time had errors in the same range as
      corresponding models based on ECL.

PMID- 21851947
TI  - Aligned nanogold assisted one step sensing and removal of heavy metal ions.
AB  - We depict a novel strategy exploiting the chemistry of metal ion adsorption for
      detection and sequestration of toxic heavy metal from processed water using gold
      nanoparticles capped with 4-aminothiophenol. The interaction between 4
      aminothiophenol capped gold nanoparticles and heavy metal ions was studied as a
      function of time and concentration using TEM, HRTEM, SEM, EDS, and I-V
      characterization. Experiments confirmed that pH is one of the crucial controlling
      parameters. Adsorption capacity was monitored using AAS, UV-vis spectroscopy and
      I-V measurement. In the absence of any alloy formation between Au and heavy metal
      ions, the desorption of the heavy metal ions from 4-aminothiophenol capped gold
      nanoparticles surface by pH modulation serves as a mean of collection of heavy
      metal ions. Experiments revealed that the concentration of heavy metal ions in
      processed water after adsorption is below the maximum permissible limit set by
      the WHO.

PMID- 21851948
TI  - Spectroscopic probing of location and dynamics of an environment-sensitive
      intramolecular charge transfer probe within liposome membranes.
AB  - The present work demonstrates the interaction of an intramolecular charge
      transfer (ICT) probe 5-(4-dimethylamino-phenyl)-penta-2,4-dienoic acid methyl
      ester (DPDAME) with liposome membranes of dimyristoyl-L-alpha-phosphatidylcholine
      (DMPC) and dimyristoyl-L-alpha-phosphatidylglycerol (DMPG) studied by steady
      state absorption, emission and time-resolved emission techniques. A huge
      hypsochromic shift together with remarkable enhancement of fluorescence quantum
      yield of the polarity sensitive ICT emission of DPDAME upon interaction with the
      lipids has been rationalized in terms of incorporation of the probe into
      hydrophobic interior of the lipids. Compelling evidences for penetration of the
      probe into the hydrocarbon interior of the lipids have been deduced from
      intertwining different experimental results e.g., micropolarity in the immediate
      vicinity of the probe in lipid environments, steady-state anisotropy, red-edge
      excitation shift (REES), fluorescence quenching experiments and time-resolved
      measurements. The rotational relaxation dynamics study of the membrane-bound
      probe unveils the impartation of high degree of motional rigidity. Wavelength
      selective emission behaviour paves way for monitoring of solvent-relaxation in
      the membranes. Overall, the ICT probe DPDAME displays its commendable sensitivity
      in deciphering the microheterogeneous environments of liposomal membranes of DMPC
      and DMPG and promises a new membrane-polarity sensitizing probe.

PMID- 21851949
TI  - Resonance scattering amplification assay of biomolecules based on the
      biomineralization of gold nanoparticles bioconjugates.
AB  - A novel method was designed for the determination of trace protein with high
      sensitivity. This sensing method combined the principle of biomineralization and
      the resonance scattering (RLS) assay of gold nanoparticles (AuNPs). AuNPs were
      synthesized in the presence of polpyropylneimine hexadeacamnie dendrimers
      (PPIHA). Meanwhile, they were superficially modified with the amine group, which
      was confirmed by Fourier transform infrared spectra (FTIR). The specific covalent
      coupling between bovine serum albumin (BSA) and amine-AuNPs assembles a
      hyperefficient crystal core. Based on the principle of biomineralization, Au(3+)
      ions were reduced to Au at the surface of bioconjugates in the HAuCl(4)
      NH(4)OH.HCl redox system. Thus, the size of AuNPs-BSA was selectively enhanced.
      Meanwhile, the concentration signal of BSA was converted to the RLS intensity of
      AuNPs, which was enhanced through this process. The selective amplification of
      RLS signal laid the foundation of the detection method, as it intensified with
      the increase of AuNPs-BSA concentration. Experimental results show that the peak
      intensity at 548 nm is proportional to the concentration gradient of the
      bioconjugates from 0.268 MUg/ml to 1.608 MUg/ml under the optimized conditions.
      Additionally, the method has high sensitivity with detection limit as low as
      0.096 MUg/ml. The specific coupling with high sensitivity and good stability of
      this method indicates its possibility for the assay of other proteins. Moreover,
      the novel method achieves quantitative detection of trace proteins, suggesting
      the potential of AuNPs-based analytical methods in further application.

PMID- 21851950
TI  - Sand consolidation with calcium phosphate-polyelectrolyte composites.
AB  - A new method for the consolidation of loose sand formations has been developed.
      The method involves in situ precipitation of a composite calcium phosphate
      polyelectrolyte salt that binds together with loose sand grains, thus resulting
      to their consolidation. Three different polyelectrolytes (PE) were tested, i.e.,
      polyacrylic acid (PAA), polyallylamine hydrochloride (PAH), and polyethylenimine
      (PEI). The effect of PE tested on the thermodynamics and the kinetics of
      precipitation of calcium phosphate salts was investigated. Three types of
      experiments were done. Investigation of the adsorption of PE on either
      hydroxyapatite (Ca(5)(PO(4))(3)OH, HAP) crystals or on sand grains. Measurement
      of the kinetics of heterogeneous nucleation of HAP on the solid substrates and
      the mechanical properties of the obtained crystals in batch experiments of low
      and high supersaturation solutions, respectively. Evaluation of the consolidation
      in sand packs in order to investigate the effectiveness of the method. The
      crystallization rates, R(p), on HAP crystals in the presence of the PE tested
      were found in the order R(p)(PAA)>R(p)(PEI)>R(p)(PAH), while nucleation and
      crystal growth on silicate sand took place only in the absence of adsorbed PE.
      PAH favored strongly the consolidation process, whereas PEI and PAA resulted in
      the formation of poorly consolidated grain agglomerates.

PMID- 21851951
TI  - Synthesis and characterization of cellulose whiskers/polymer nanocomposite
      dispersion by mini-emulsion polymerization.
AB  - Stable film-forming nanocomposite particles with diameters ranging from 120 to
      300 nm, based on polybutylmethacrylate (PBMA) and cellulose whiskers in water
      dispersions, were successfully synthesized in one step through mini-emulsion
      polymerization. The nanocomposite dispersion with a solid content of 25 wt.% and
      up to 5 wt.% of nanofiller loading was prepared by in situ polymerization, in the
      presence of the whiskers using dodecylpyridinium chloride (DPC), as a cationic
      surfactant, and 2,2-azobis(isobutyronitrile) (AIBN), as initiator. The
      electrostatic interaction between the positively charged droplets and negatively
      charged whiskers ensured the anchoring of the nanofiller around the polymer
      particles. The ensuing dispersions were characterized by Dynamic Light Scattering
      (DLS), zeta-Potential Measurements, and Field-Emission Scanning Electron
      Microscopy (FE-SEM). After the film formation process, the nanocomposite film
      exhibits a high transparency, denoting the good dispersion of the whiskers
      throughout the matrix.

PMID- 21851952
TI  - The development of regret.
AB  - In two experiments, 4- to 9-year-olds played a game in which they selected one of
      two boxes to win a prize. On regret trials the unchosen box contained a better
      prize than the prize children actually won, and on baseline trials the other box
      contained a prize of the same value. Children rated their feelings about their
      prize before and after seeing what they could have won if they had chosen the
      other box and were asked to provide an explanation if their feelings had changed.
      Patterns of responding suggested that regret was experienced by 6 or 7 years of
      age; children of this age could also explain why they felt worse in regret trials
      by referring to the counterfactual situation in which the prize was better. No
      evidence of regret was found in 4- and 5-year-olds. Additional findings suggested
      that by 6 or 7 years, children's emotions were determined by a consideration of
      two different counterfactual scenarios.

PMID- 21851953
TI  - Bloody urine after minor trauma in a child: isolated renal injury versus
      congenital anomaly?

PMID- 21851954
TI  - Instrumental activities of daily living in Parkinson's disease dementia as
      compared with Alzheimer's disease: relationship to motor disability and cognitive
      deficits: a pilot study.
AB  - OBJECTIVE: Our objective was to assess which clinical factors contribute most to
      the impairment of instrumental activities of daily living (IADL) in patients with
      dementia in Parkinson's disease (PDD) as compared to age- and dementia duration
      matched patients with Alzheimer's disease (AD). METHODS: Eighteen consecutive
      subjects (16 men, 2 women) with PDD and 30 age- and dementia duration-matched
      subjects with AD (13 men, 17 women) were recruited. The groups were not matched
      for their Mini-Mental Status Examination (MMSE) score. Neuropsychiatric,
      cognitive and motor data were collected in a routine clinical setting using the
      MMSE, four brief tests of the seven minute screen (i.e. the Benton Temporal
      Orientation, Grober and Buschke's enhanced cued recall, verbal fluency, and the
      clock drawing test), the Neuropsychiatric Inventory, a modified version of the
      Hoehn and Yahr scale and a Czech modified version of Lawton's IADL questionnaire.
      The IADL scores were correlated with clinical variables in each group. RESULTS:
      There were no differences in IADL abilities between both groups. A significant
      association was found between IADL and cognitive impairment as measured by
      screening tests in the AD group. In the PDD group, IADL scores were particularly
      correlated with PD duration (r=-0.73, p<0.01) and the Hoehn and Yahr score (r=
      0.59, p<0.01). CONCLUSION: Our pilot study results show that motor deficits
      remain the major contributor to IADL impairment in PDD.

PMID- 21851955
TI  - Absence of the OPTN mutation in a patient with ALS and familial primary open
      angle glaucoma.
AB  - The optineurin (OPTN) gene, known to be implicated in primary open-angle glaucoma
      (POAG), is the more recent genetic factor linked to ALS. We report the case of a
      75year-old man who developed ALS and whose medical history was dominated by a
      familial POAG. The absence of OPTN gene mutation in a patient who suffered from
      two conditions linked to mutations of this gene does not support involvement of
      OPTN in ALS.

PMID- 21851956
TI  - Placement of 2 implantable centrifugal pumps to serve as a total artificial heart
      after cardiectomy.

PMID- 21851957
TI  - Cytotoxic activity of withanolides isolated from Tunisian Datura metel L.
AB  - Withanolide-type steroids, withametelin Q (1) and 12alpha-hydroxydaturametelin B
      (2) along with three known withanolides, were isolated from leaves of Datura
      metel L. (Solanaceae). The respective structures, characterized mainly by NMR
      spectroscopy, were identified as (20R,22R,24R)-21,24-epoxy-1alpha,3beta
      dihydroxywitha-5,25(27)-dienolide-3-O-beta-D-glucopyranoside (1) and
      (20R,22R,24R)-12alpha,21,27-trihydroxy-1-oxowitha-2,5,24-trienolide-27-O-beta-D
      glucopyranoside (2). The cytotoxicity of isolated compounds was evaluated against
      human lung carcinoma cells (A549) and human colorectal adenocarcinoma cells (DLD
      1), respectively. Compound 2 exhibited cytotoxicity against A549 and DLD-1 cell
      lines, with IC50 values of 7 and 2.0 MUM, respectively. However, for compounds 6
      and 7, cytotoxicities were higher against DLD-1 cells with IC(50) values of 0.6
      and 0.7 MUM. Both compounds blocked the cell cycle in the S-phase and induced
      apoptosis.

PMID- 21851959
TI  - Intrinsic disorder in the common N-terminus of human adenovirus 5 E1B-55K and its
      related E1BN proteins indicated by studies on E1B-93R.
AB  - The E1B transcription unit of human adenovirus encodes at least five different
      proteins generated by alternative splicing of a common E1B precursor mRNA. E1B
      156R, -93R and -84R contain individual carboxy termini but share a common amino
      terminus. To acquire data on the structure of the amino terminus we performed
      biophysical analyses on E1B-93R. We show that E1B-93R is mostly unstructured and
      fulfills the criteria of an intrinsically disordered protein (IDP). The intrinsic
      disorder in the amino terminus of these proteins is evolutionary conserved in all
      seven human adenovirus species. As IDPs comprise a rapidly growing family of
      proteins which, despite their lack of a well defined structure, often fulfill
      essential regulatory functions, the observations described here might open up a
      new avenue for the understanding of the regulation and functions of E1B proteins,
      in particular the multifunctional E1B-55K oncoprotein.

PMID- 21851958
TI  - A single amino acid substitution in the C4 region in gp120 confers enhanced
      neutralization of HIV-1 by modulating CD4 binding sites and V3 loop.
AB  - Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based
      vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified
      from a recently infected Indian patient showing exceptional neutralization
      sensitivity to autologous plasma in contrast to other autologous Envs obtained at
      the same time point. By constructing chimeric Envs and fine mapping between
      sensitive and resistant Env clones, we found that substitution of highly
      conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the
      C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped
      viruses to autologous and heterologous plasma antibodies. When tested against
      monoclonal antibodies targeting different sites in gp120 and gp41, Envs
      expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies
      and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed
      similar neutralization phenotype, indicating that M424 in C4 region induces
      exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.

PMID- 21851960
TI  - Including greenhouse gas emissions during benchmarking of wastewater treatment
      plant control strategies.
AB  - The main objective of this paper is to demonstrate how greenhouse gas (GHG)
      emissions can be quantified during the evaluation of control strategies in
      wastewater treatment plants (WWTP). A modified version of the IWA Benchmark
      Simulation Model No 2 (BSM2G) is hereby used as a simulation case study. Thus,
      the traditional effluent quality index (EQI), operational cost index (OCI) and
      time in violation (TIV) used to evaluate control strategies in WWTP are
      complemented with a new dimension dealing with GHG emissions. The proposed
      approach is based on a set of comprehensive models that estimate all potential on
      site and off-site sources of GHG emissions. The case study investigates the
      overall performance of several control strategies and demonstrates that
      substantial reductions in effluent pollution, operating costs and GHG emissions
      can be achieved when automatic control is implemented. Furthermore, the study is
      complemented with a scenario analysis that examines the role of i) the dissolved
      oxygen (DO) set-point, ii) the sludge retention time (SRT) and iii) the organic
      carbon/nitrogen ratio (COD/N) as promoters of GHG emissions. The results of this
      study show the potential mechanisms that promote the formation of CO2, CH4 and
      N2O when different operational strategies are implemented, the existing synergies
      and trade-offs amongst the EQI, the OCI and TIV criteria and finally the need to
      reach a compromise solution to achieve an optimal plant performance.

PMID- 21851961
TI  - PM10 source apportionment in Milan (Italy) using time-resolved data.
AB  - In this work Positive Matrix Factorization (PMF) was applied to 4-hour resolved
      PM10 data collected in Milan (Italy) during summer and winter 2006. PM10
      characterisation included elements (Mg-Pb), main inorganic ions (NH(4)(+), NO(3)(
      ), SO(4)(2-)), levoglucosan and its isomers (mannosan and galactosan), and
      organic and elemental carbon (OC and EC). PMF resolved seven factors that were
      assigned to construction works, re-suspended dust, secondary sulphate, traffic,
      industry, secondary nitrate, and wood burning. Multi Linear Regression was
      applied to obtain the PM10 source apportionment. The 4-hour temporal resolution
      allowed the estimation of the factor contributions during peculiar episodes,
      which would have not been detected with the traditional 24-hour sampling
      strategy.

PMID- 21851963
TI  - Aerobic phosphorus release from shallow lake sediments.

PMID- 21851962
TI  - Unusually high (210)Po activities in the surface water of the Zhubi Coral Reef
      Lagoon in the South China Sea.
AB  - Recent researches revealed the exciting application of (210)Po in tracing carbon
      and nitrogen cycling in the coral reef system. In order to quantify the recycling
      of particulate organic nitrogen (PON), both (210)Po and (210)Pb were examined at
      both high and low tides in the Zhubi Coral Reef lagoon, the South China Sea.
      Unusually, much higher (210)Po activities and (210)Po/(210)Pb ratios, in
      comparison with those found in the open seawater and the lagoon subsurface water,
      showed additional input of (210)Po besides production from in situ(210)Pb in the
      lagoon surface water. Statistical analysis identified that the reef flat seawater
      was the additional (210)Po source. Based on a mass balance model, the input rates
      of (210)Po varied from 0.04 Bq m(-3)year(-1) to 8.41 Bq m(-3)year(-1). On
      average, the additional (210)Po contributed more than 60% of the total (210)Po.
      The particulate (210)Po significantly correlated with the concentrations of PON,
      indicating that diffusion of (210)Po from sediment could be used to quantify the
      recycling of nitrogen. The average input rate of nitrogen was 16 mmol m(-3)year(
      1), which can support up to 11% of the primary production rate. These results
      suggested that the unusual behavior of (210)Po could provide new insight into the
      nitrogen recycling in the coral reef system.

PMID- 21851964
TI  - Influence of soil properties on trace element availability and plant accumulation
      in a Mediterranean salt marsh polluted by mining wastes: implications for
      phytomanagement.
AB  - The aims of this study were to determine the factors which control metal and As
      phytoavailability in the different microenvironments (Sand Dunes, Salt Flat, Dry
      River and Shrubs) present at a Mediterranean salt marsh polluted by mining
      wastes. We performed a field study following a plot sampling survey. The analyses
      of soil parameters (pH, electrical conductivity (EC), organic carbon contents,
      etc.), total metal and As concentrations and their phytoavailability assessed
      with EDTA were related to each microenvironment and the corresponding plant
      species uptake. The averages of pH and EC were slightly alkaline (pH ~ 7.5) and
      saline (~ 2.2 to 17.1 dS m(-1)) respectively. The soil samples from the Salt Flat
      subzone showed the highest metal concentrations (e.g. 51 mg kg(-1) Cd, 11,600 mg
      kg(-1) Pb) while for As, the highest concentrations occurred in the Dry River
      (380 mg kg(-1) As). The total metal and EDTA-extractable concentrations occurred
      as it follows: Salt Flat>Dry River>Degraded Dunes>Shrubs. In relation to plant
      metal and As accumulation, the highest root concentrations were obtained in the
      species from the Salt Flat subzone: ~17 mg kg(-1) As, ~620 mg kg(-1) Pb, for
      both, Juncus maritimus and Arthrocnemum macrostachyum. However the highest metal
      and As shoot concentrations occurred in species from the Sand Dunes: ~23 mg kg(
      1) As ~270 mg kg(-1) Pb for Dittrichia viscosa; ~23 mg kg(-1) As, ~390 mg kg(-1)
      Zn for Crucianella maritima. The occurrence of edaphic gradients including
      salinity and texture determined the vegetation distribution. However, it cannot
      be concluded that there was a disturbance due to metal(loid)s soil concentrations
      in terms of vegetation composition except in the Degraded Dunes and Dry River.
      The higher EDTA-extractable concentrations were coincidental with the most saline
      soils but this did not result in higher metal(loid)s plant accumulation.

PMID- 21851965
TI  - A study of the mechanism of in vitro cytotoxicity of metal oxide nanoparticles
      using catfish primary hepatocytes and human HepG2 cells.
AB  - Nanoparticles (NPs), including nanometal oxides, are being used in diverse
      applications such as medicine, clothing, cosmetics and food. In order to promote
      the safe development of nanotechnology, it is essential to assess the potential
      adverse health consequences associated with human exposure. The liver is a target
      site for NP toxicity, due to NP accumulation within it after ingestion,
      inhalation or absorption. The toxicity of nano-ZnO, TiO(2), CuO and Co(3)O(4) was
      investigated using a primary culture of channel catfish hepatocytes and human
      HepG2 cells as in vitro model systems for assessing the impact of metal oxide NPs
      on human and environmental health. Some mechanisms of nanotoxicity were
      determined by using phase contrast inverted microscopy, 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assays, reactive oxygen species (ROS)
      assays, and flow cytometric assays. Nano-CuO and ZnO showed significant toxicity
      in both HepG2 cells and catfish primary hepatocytes. The results demonstrate that
      HepG2 cells are more sensitive than catfish primary hepatocytes to the toxicity
      of metal oxide NPs. The overall ranking of the toxicity of metal oxides to the
      test cells is as follows: TiO(2)<Co(3)O(4)<ZnO<CuO. The toxicity is due not only
      to ROS-induced cell death, but also to damages to cell and mitochondrial
      membranes.

PMID- 21851966
TI  - Impaired glucose metabolism and type 2 diabetes are associated with
      hypercoagulability: potential role of central adiposity and low-grade
      inflammation--the Hoorn Study.
AB  - INTRODUCTION: Type 2 diabetes (DM2) is associated with greater risk for
      cardiovascular disease (CVD), which may, at least partially, be explained by
      prothrombotic alterations. We therefore investigated; first, the extent to which
      individuals with impaired glucose metabolism (IGM) and/or DM2 had greater levels
      of thrombin generation than those with normal glucose metabolism (NGM); and
      second, whether any differences were independent of other cardiovascular risk
      factors, such as smoking, hypertension, dyslipidaemia, (micro)albuminuria,
      glycemic control and (central) adiposity, and/or were potentially 'mediated' by
      low-grade inflammation (high-sensitivity C-reactive protein (hsCRP)). MATERIALS
      AND METHODS: We studied 744 individuals from the Hoorn Study (275 NGM, 176 IGM
      and 293 DM2, mean age 68.6 +/- 7.1 years). Thrombin generation in platelet-poor
      plasma was measured using the Calibrated Automated Thrombogram and three
      parameters were derived: lag time, peak height and endogenous thrombin potential
      (ETP). Data were analyzed with multiple linear regression analyses. RESULTS:
      After adjustment for age, sex, prior CVD and smoking status, individuals with IGM
      or DM2 had a longer lag time [beta = 0.14 min (95% CI: 0.02; 0.26)], higher peak
      height [beta = 7.29 nM (-1.33; 15.91)] and ETP [beta = 35.65 nM*min (0.97;
      70.34)] than those with NGM. These differences were attenuated to beta = 0.06 min
      (-0.07; 0.19), 3.82 nM (-5.46; 13.10) and 16.34 nM*min (-20.92; 53.59),
      respectively, when further adjusted for waist circumference and hsCRP.
      CONCLUSION: Individuals with IGM or DM2 had up to 4% higher thrombin generation
      compared with NGM, which may be explained, to a great extent, by the greater
      levels of central adiposity and related low-grade inflammation characterizing
      these individuals.

PMID- 21851967
TI  - In vitro study of the anticoagulant effects of edoxaban and its effect on
      thrombin generation in comparison to fondaparinux.
AB  - INTRODUCTION: Edoxaban, an oral direct factor Xa (FXa) inhibitor, is in Phase III
      development for prevention and treatment of thromboembolic disorders.
      Fondaparinux is an approved indirect FXa inhibitor. This study compared the
      effects of edoxaban and fondaparinux on thrombin generation (TG) using the
      calibrated automated thrombogram (CAT). Secondary objectives included evaluation
      of edoxaban and inhibition of coagulation parameters (prothrombin time [PT],
      activated partial thromboplastin time [aPTT]), anti-FXa activity and clotting
      times. MATERIALS AND METHODS: Pooled citrated platelet-poor plasma from healthy
      subjects was spiked with edoxaban (0.02-3.65 MUM) or fondaparinux (0.15-1.18
      MUM). Parameters of TG were calculated using Thrombinoscope software. PT ratios
      and aPTT were measured in the presence of different thromboplastin reagents.
      Exogenous anti-FXa was measured using Rotachrom HBPM (Stago) and a specific assay
      developed for direct FXa inhibitors (Hyphen BioMed). RESULTS: Edoxaban exhibited
      a 3-fold greater concentration-dependent effect than fondaparinux across TG
      parameters (except endogenous thrombin potential). Edoxaban also produced a
      concentration-dependent prolongation of PT ratio and aPTT. The magnitude of
      concentration-dependent increase was related to thromboplastin reagent. In
      contrast to edoxaban, fondaparinux was inactive on these clotting tests. Linear
      correlations were observed between plasma concentration of edoxaban and anti-FXa
      activity and results of clotting time assays. CONCLUSIONS: TG evaluation by the
      CAT method, coagulation tests, and anti-FXa and clotting assays demonstrated
      concentration-dependent effects of edoxaban. The PT and aPTT prolongation are
      reagent dependent; correction of PT ratio by international normalized ratio does
      not reduce variability in response. The greater effect of edoxaban vs.
      fondaparinux may be related to the broader activity of direct FXa inhibitors
      compared with indirect FXa inhibitors.

PMID- 21851968
TI  - Treatment with unfractionated heparin attenuates coagulation and inflammation in
      endotoxemic mice.
AB  - INTRODUCTION: In the pathogenesis of sepsis, inflammation and coagulation play a
      pivotal role. In addition to the anticoagulant activity, unfractionated heparin
      (UFH) has important immunomodulatory properties. However, different studies have
      reported conflicting effects on sepsis in association with heparin. The objective
      of this study is to determine whether UFH is able to reduce endotoxin-induced
      inflammation and coagulation in mice or produce improved outcome. METHODS:
      C57BL/6J mice were randomly divided into two groups. Experimental mice were given
      intravenous injection of 8 units/20 g body weight UFH (heparin sodium) diluted in
      20 MUl sterile saline while the control mice received vehicle sterile saline
      only. They were injected with LPS (30 mg/kg, i.p.) 0.5h later. Blood was
      collected and Livers were harvested at 3 and 6h for analysis. In survival
      studies, a separate group of mice were treated with 8 units/20 g UFH (n=20) or
      sterile saline (n=20) given intravenously at 1, 12, 24 and 36 hours after LPS
      injection. Mice were monitored every 12 hours for a maximum of 72 hrs. RESULTS:
      1) Pretreatment of mice with UFH strongly reduced the levels of TNF-alpha, IL
      1beta and TAT in plasma at 3 and 6h; 2) Pretreatment of mice with UFH inhibited
      the expression of TNF-alpha, IL-1beta and tissue factor genes in blood cells at
      3h; 3) UFH pretreatment dramatically diminished LPS-induced neutrophil
      sequestration (at 3 and 6h) , thrombi formation and fibrin(ogen) deposition in
      the liver (at 6h). 4) The UFH-pretreated group exhibited significantly lower
      levels of ALT and CRE at 6h. 5) Treatment with UFH could prevent mortality
      associated with endotoxin challenge. CONCLUSION: These data suggest that UFH
      attenuates inflammation and coagulation and prevents lethality in endotoxemic
      mice.

PMID- 21851969
TI  - Variability of INR and its relationship with mortality, stroke, bleeding and
      hospitalisations in patients with atrial fibrillation.
AB  - BACKGROUND - RATIONALE FOR STUDY: Atrial fibrillation is associated with an
      increased risk of stroke and mortality which is reduced by treatment with
      warfarin. The most commonly used tool to assess the effectiveness of warfarin
      therapy is the time in therapeutic range (TTR) of International Normalised Ratio
      (INR) 2.0-3.0. Our aim was to study whether INR variability, as assessed by the
      standard deviation of transformed INR (SDT(INR)) is more prognostically important
      than the TTR. METHODS AND RESULTS: We studied 19,180 patients with atrial
      fibrillation on warfarin therapy to evaluate the association of TTR and that of
      SDT(INR) with all-cause mortality, stroke, bleeding and hospitalisation. The
      SDT(INR) was more prognostically important than the TTR. One standard deviation
      (SD) higher of SDT(INR) had a hazard ratio (HR) of 1.59 (95% CI 1.52-1.66) of
      mortality compared with 1.18 (95% CI 1.13-1.24) for one SD lower of TTR. For the
      other 3 events the HR was also higher for the SDT(INR) than for the TTR (stroke
      1.30 (95% CI 1.22-1.39) vs. 1.06 (95% CI 1.00-1.13), bleeding 1.27 (95% CI 1.20
      1.35) vs. 1.07 (95% CI 1.01-1.14) , hospitalisation 1.47 (95% CI 1.45-1.49) vs.
      1.13 (95% CI 1.10-1.15). When both metrics were included in the same analysis
      only the SDT(INR) was of significant predictive value. CONCLUSIONS: The SDT(INR)
      is a better predictor of mortality, stroke, bleeding and hospitalisation than the
      TTR in patients with atrial fibrillation receiving warfarin therapy.

PMID- 21851970
TI  - Echocardiographic evaluation for pulmonary hypertension after recurrent pulmonary
      embolism.
AB  - INTRODUCTION: Although recurrent venous thromboembolism is a known risk factor
      for chronic thromboembolic pulmonary hypertension (CTEPH), the prevalence of
      CTEPH after recurrent pulmonary embolism (PE) is not clear. MATERIALS AND
      METHODS: A cohort screening study was performed to clarify the prevalence of
      echocardiographic variables indicating pulmonary hypertension (PH) in patients
      after recurrent PE. RESULTS: 43 survivors of recurrent PE could be enrolled.
      Echocardiography indicated likely PH in 7 patients. In 5 out of these 7 patients
      PH was likely and the left ventricular function was normal. Right heart
      catheterization and ventilation/perfusion lung scan were performed in these
      patients. CTEPH could be diagnosed in all 5 patients (11.6% of the total study
      population). No World Health Organisation functional class (WHO-FC) I patient was
      suspected to have CTEPH. CTEPH was significantly more often diagnosed in WHO-FC
      III than in WHO-FC II (33.3% versus 9.5%; p=0.024). CONCLUSIONS: CTEPH was found
      to be a frequent sequela in patients with recurrent PE. The prevalence of CTEPH
      is dependent on the patient's functional class. Evaluation for PH might be useful
      in symptomatic patients after recurrent PE.

PMID- 21851972
TI  - Food protein-induced enterocolitis to hen's egg.

PMID- 21851971
TI  - Haplotypes of the endothelial protein C receptor gene and Behcet's disease.
AB  - INTRODUCTION: Behcet's disease is a vasculitis of unknown cause in which
      thrombosis occurs in about 25% of patients. Two haplotypes of the endothelial
      protein C receptor gene, H1 and H3, are associated with the risk of thrombosis.
      Thus, the objective of this study was to evaluate the influence of these
      haplotypes on the thrombosis risk in Behcet's disease. MATERIAL AND METHODS: We
      evaluated the H1 and H3 haplotypes in 87 patients with Behcet's disease, 19 with
      and 68 without a history of thrombosis, and in 260 healthy individuals. We also
      measured protein C, activated protein C, and soluble endothelial protein C
      receptor levels in all individuals. RESULTS: The presence of the H1 haplotype
      seemed to protect Behcet's patients against thrombosis (odds ratio 0.21; 95% CI
      0.1-0.8; p=0.023), whereas the frequency of the H3 haplotype was lower in
      patients than in control individuals (0.19; 0.1-0.5; p=0.006). Furthermore, the
      H1 haplotype was associated with increased levels of activated protein C, whereas
      the H3 haplotype was associated with the highest soluble endothelial protein C
      levels. Moreover, activated protein C levels were lower in patients with than in
      patients without posterior uveitis (p<0.001). CONCLUSIONS: These findings
      indicate that the H1 haplotype protects Behcet's patients from thrombosis, likely
      via increased levels of activated protein C, whereas individuals carrying the H3
      haplotype seem to be protected from the clinical manifestations associated with
      Behcet's disease, probably via increased soluble endothelial protein C levels.

PMID- 21851973
TI  - Feeling angry and acting angry: different effects of autonomy-connectedness in
      boys and girls.
AB  - This study examined effects of the autonomy-connectedness components sensitivity
      to others, self-awareness and capacity for managing new situations on anger
      experience versus anger expression in adolescent boys and girls. One hundred
      thirty-one high school students were randomly assigned to an anger-inducing or
      neutral condition using the Dictator Game. Whereas after anger induction boys
      experienced and expressed anger independent of autonomy-connectedness, girls'
      anger experience depended on the level of sensitivity to others: girls
      experienced increased anger only when they scored high on sensitivity to others.
      However, girls' expression of anger did not depend on the level of sensitivity to
      others. Effects of self-awareness and capacity for managing new situations were
      found when anger was not induced. This study contributed to emotion regulation
      research by showing differences in anger experience and anger expression as a
      function of autonomy-connectedness in boys and girls.

PMID- 21851974
TI  - Effects of education on harm-reduction programmes.

PMID- 21851975
TI  - Should antipsychotics take pole position in mania treatment?

PMID- 21851976
TI  - Comparative efficacy and acceptability of antimanic drugs in acute mania: a
      multiple-treatments meta-analysis.
AB  - BACKGROUND: Conventional meta-analyses have shown inconsistent results for
      efficacy of pharmacological treatments for acute mania. We did a multiple
      treatments meta-analysis, which accounted for both direct and indirect
      comparisons, to assess the effects of all antimanic drugs. METHODS: We
      systematically reviewed 68 randomised controlled trials (16,073 participants)
      from Jan 1, 1980, to Nov 25, 2010, which compared any of the following
      pharmacological drugs at therapeutic dose range for the treatment of acute mania
      in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin,
      haloperidol, lamotrigine, lithium, olanzapine, quetiapine, risperidone,
      topiramate, and ziprasidone. The main outcomes were the mean change on mania
      rating scales and the number of patients who dropped out of the allocated
      treatment at 3 weeks. Analysis was done by intention to treat. FINDINGS:
      Haloperidol (standardised mean difference [SMD] -0.56 [95% CI -0.69 to -0.43]),
      risperidone (-0.50 [-0.63 to -0.38), olanzapine (-0.43 [-0.54 to -0.32], lithium
      (-0.37 [-0.63 to -0.11]), quetiapine (-0.37 [-0.51 to -0.23]), aripiprazole (
      0.37 [-0.51 to -0.23]), carbamazepine (-0.36 [-0.60 to -0.11], asenapine (-0.30 [
      0.53 to -0.07]), valproate (-0.20 [-0.37 to -0.04]), and ziprasidone (-0.20 [
      0.37 to -0.03]) were significantly more effective than placebo, whereas
      gabapentin, lamotrigine, and topiramate were not. Haloperidol had the highest
      number of significant differences and was significantly more effective than
      lithium (SMD -0.19 [95% CI -0.36 to -0.01]), quetiapine (-0.19 [-0.37 to 0.01]),
      aripiprazole (-0.19 [-0.36 to -0.02]), carbamazepine (-0.20 [-0.36 to -0.01]),
      asenapine (-0.26 [-0.52 to 0.01]), valproate (-0.36 [-0.56 to -0.15]),
      ziprasidone -0.36 [-0.56 to -0.15]), lamotrigine (-0.48 [-0.77 to -0.19]),
      topiramate (-0.63 [-0.84 to -0.43]), and gabapentin (-0.88 [-1.40 to -0.36]).
      Risperidone and olanzapine had a very similar profile of comparative efficacy,
      being more effective than valproate, ziprasidone, lamotrigine, topiramate, and
      gabapentin. Olanzapine, risperidone, and quetiapine led to significantly fewer
      discontinuations than did lithium, lamotrigine, placebo, topiramate, and
      gabapentin. INTERPRETATION: Overall, antipsychotic drugs were significantly more
      effective than mood stabilisers. Risperidone, olanzapine, and haloperidol should
      be considered as among the best of the available options for the treatment of
      manic episodes. These results should be considered in the development of clinical
      practice guidelines. FUNDING: None.

PMID- 21851977
TI  - System A activity and vascular function in the placental-specific Igf2 knockout
      mouse.
AB  - OBJECTIVES: Deletion of the placental-specific P0 transcript of the insulin-like
      growth factor gene (Igf2) reduces placental growth from early pregnancy onwards.
      In Igf2 P0 knockout fetuses (P0), maternofetal flux of (14)C
      methylaminoisobutyric acid ((14)C-MeAIB) mediated by system A amino acid
      transporter activity is increased at embryonic day 16 (E16), but this stimulation
      is not sustained, and by E19, fetal growth restriction (FGR) ensues. Here, we
      investigated whether upregulated (14)C-MeAIB transfer does occur concomitantly
      with a change in System A amino acid transporter activity and whether altered
      uteroplacental vascular function contributes to the FGR. We tested the hypothesis
      that FGR in P0 mice is attributable to altered nutrient transport rather than
      aberrant uteroplacental vascular function. METHODS: Plasma membrane vesicles were
      isolated from placentas of P0 and wild-type (WT) fetuses at E16 and E19. System A
      amino acid transporter activity was measured as sodium-dependent (14)C-MeAIB
      uptake over 60s. Wire myography was performed on uterine artery branches
      supplying P0 or WT implantation sites and agonist-induced constriction and
      dilation measured. RESULTS: Sodium-dependent uptake of (14)C-MeAIB (at 60s) was
      significantly (P < 0.05) higher in P0 compared to WT vesicles at E16; at E19
      (14)C-MeAIB uptake was similar between P0 and WT. Uterine artery branch vascular
      reactivity was comparable between groups. CONCLUSIONS: System A activity in the
      maternal-facing plasma membrane of syncytiotrophoblast layer II underpins the
      adaptations observed in the transplacental MeAIB flux of P0 mice. Unaltered
      uterine artery vascular function suggests that the FGR phenotype of P0 fetuses is
      primarily due to deficient placental nutrient exchange capacity.

PMID- 21851978
TI  - Diagnostic testing, treatment, cost of care, and survival among registered and
      non-registered patients with myelodysplastic syndromes.
AB  - Considering current reliance on cancer registry data, we sought to assess the
      potential for bias in myelodysplastic syndrome (MDS) registration using SEER
      Medicare data 2001-2005. Using a validated claims-based algorithm, we identified
      and compared registered and non-registered MDS patients, and found that median
      cumulative survival was 18 and 28 months, 74% and 64% used erythropoiesis
      stimulating agents (ESAs), and average 6-month health care cost was $24,249 and
      $21,750, respectively. While most non-registered MDS patients showed resource
      utilization and survival characteristics consistent with lower-risk MDS, a subset
      was registered as acute myeloid leukemia (7.6%) and accounted for early
      mortality.

PMID- 21851979
TI  - Cues of paternal uncertainty and father to child physical abuse as reported by
      mothers in Rio de Janeiro, Brazil.
AB  - OBJECTIVE: Paternity is uncertain, so if paternal feelings evolved to promote
      fitness, we might expect them to vary in response to variables indicative of
      paternity probability. We therefore hypothesized that the risk of lapses of
      paternal affection, including abusive assaults on children, will be exacerbated
      by cues of non-paternity. METHODS: Cross-sectional study of 331 Brazilian
      mothers, interviewed about 1 focal child (age 1-12) residing with her and the
      putative father. Child physical abuse was assessed using the Conflict Tactic
      Scales: Parent Child (CTSPC). Two potential cues of (non) paternity were (1)
      whether the parents co-resided when the child was conceived, and (2) whether
      third parties allegedly commented on father-child resemblance. Data were analyzed
      through multiple logistic regressions. RESULTS: Mothers reported child physical
      abuse by 15.9% (95% CI 4.6-27.1) of fathers who had not cohabited with them at
      conception, compared to 5.9% (95% CI 3.1-8.7) of those who had. The odds ratio
      for abuse by fathers who had not cohabited at conception in relation to those who
      had-adjusted for income, education, age, sex of child, whether child was first
      born, household size, time father spent with child, and alcohol abuse and drug
      use by father-was 4.3 (95% CI 1.4-13.8). Mothers reported abuse of 7.0% (95% CI
      4.0-10.0) of children who purportedly resembled their fathers, versus 8.7% (95%
      CI 0.2-17.1) of those who did not. CONCLUSION: According to maternal reports, not
      having co-resided at conception quadrupled the chance of child physical abuse by
      currently co-residing Brazilian fathers. The reported prevalence of abuse was
      unrelated to reported allegations of father-child resemblance.

PMID- 21851980
TI  - Validation trial of Japan's zinc water quality standard for aquatic life using
      field data.
AB  - This study sought to validate Japan's zinc water quality standard for aquatic
      life (algae and benthic invertebrates) based on field survey data. The effects of
      zinc on aquatic life, especially algae and benthic invertebrates, were
      investigated mainly in water areas with upstream basins that contain mines. Seven
      biological indicators (number of cells or individuals, number of taxa, number of
      EPT taxa, number of collector-gatherer taxa of benthic invertebrates, and Simpson
      index, Shannon-Weiner index, and Margalef index for algae and benthic
      invertebrates) were analyzed with respect to zinc concentrations and the zinc
      toxic equivalent quantity (Zn-TEQ), and additive contribution from other metals
      was assumed. The results showed that the number of taxa of algae and benthic
      invertebrates significantly decreased with increases in zinc concentration and Zn
      TEQ. For benthic invertebrates, six of the metrics (all except the number of
      individuals) tended to decrease with increases in zinc concentration and Zn-TEQ.
      The effect level of biocenosis (ELB) was defined as the concentration at which
      the metrics decrease significantly with Wilcoxon's rank sum test. The ELB
      calculated for zinc was in the range of 16-54 MUg/L for zinc concentration and 38
      50 MUg/L for Zn-TEQ; thus, Japan's environmental zinc standard for the protection
      of aquatic life, at 30 MUg/L, was found to be a level consistent with these
      results.

PMID- 21851981
TI  - A multiple biomarker approach to investigate the effects of copper on the marine
      bivalve mollusc, Mytilus edulis.
AB  - While copper (Cu) is considered to be an essential trace element for many
      organisms, overexposure to this metal can induce a wide spectrum of effects
      including DNA damage. Given that Cu is a highly relevant contaminant in the
      marine environment, we aimed to evaluate the induction of DNA strand breaks
      (using the comet assay) in haemocytes and concurrently also determined biological
      responses at higher levels of biological organisation in bivalve molluscs,
      Mytilus edulis, following exposure for 5 days to a range of environmentally
      realistic levels of Cu (18-56 MUg l(-1)). Prior to evaluation of genetic damage,
      the maximum tolerated concentration (MTC) was also determined, which was found to
      be (100 MUg l(-1)) above which complete mortality over the exposure period was
      observed. In addition to DNA damage, levels of glutathione in adductor muscle
      extracts, histopathological examination of various organs (viz., adductor muscle,
      gills and digestive glands) and clearance rates as a physiological measure at
      individual level were also determined. Furthermore, tissue-specific accumulation
      and levels of Cu in water samples were also determined using ICP-MS. There was a
      strong concentration-dependant induction for DNA damage and total glutathione
      levels increased by 1.8-fold at 56 MUg l(-1) Cu. Histological examination of the
      organs showed qualitatively distinct abnormalities. Clearance rate also showed a
      significant decrease compared to controls even at the lowest concentration (i.e.
      18 MUg l(-1); P=0.003). Cu levels in adductor muscle (P=0.012), digestive gland
      (P=0.008) and gills (P=0.002) were significantly higher than in the control. The
      multi-biomarker approach used here suggests that in some cases clear
      relationships exist between genotoxic and higher level effects, which could be
      adopted as an integrated tool to evaluate different short and long-term toxic
      effects of pollutants.

PMID- 21851982
TI  - The antioxidant effect of wheat germ oil on subchronic coumaphos exposure in
      mice.
AB  - Forty-eight male Balb/C mice, allocated to 4 equal groups, constituted the
      material of the study. The first group was maintained as the control group and
      was administered solely with a vehicle, which was used to dissolve coumaphos in
      the third and fourth groups. The second group was administered with 1.5
      ml/kg.bw/day (~1400 mg/kg.bw/day) of wheat germ oil. The third group received
      5.5mg/kg.bw/day (1/10 LD50(oral)) of coumaphos. Finally, the fourth group was
      given both coumaphos and wheat germ oil at the doses indicated above. In all
      groups, the compounds were given directly into the stomach using a gastric tube,
      and treatment was continued for a period of 45 days. At the end of the 45th day,
      the liver, lungs, kidneys, brain, heart and spleen were extirpated in all of the
      animals. Tissue homogenates prepared from the tissue specimens were analysed for
      malondialdehyde (MDA) levels and catalase (CAT), superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) activities. In conclusion, it was determined that
      coumaphos led to adverse alterations in the majority of the oxidative stress
      markers investigated. The administration of wheat germ oil alleviated the
      coumpahos-induced adverse effects detected in the tissues examined.

PMID- 21851983
TI  - In utero exposure to polychlorinated biphenyls and reduced neonatal physiological
      development from Guiyu, China.
AB  - Primitive electronic-waste recycling resulted in serious pollution of
      polychlorinated biphenyls (PCBs) in the environment of Guiyu, China. We aimed to
      assess body burdens of PCBs and potential health risks for neonates. Umbilical
      cord blood (UCB) samples were collected from Guiyu, and the control area of
      Chaonan, China. PCBs in UCB were determined by gas chromatography coupled with
      mass spectrometry. The median ?PCBs concentration was 338.56 ng g-1 lipid in UCB
      samples from Guiyu, vs. 140.16 ng g-1 lipid in samples from Chaonan. Mothers'
      involvement in electronic-waste recycling activities and house used as family
      workshop were the significant factors that contributed to ?PCBs level. Some
      individual PCB congeners were found to correlate with reduced neonatal height,
      weight, Apgar scores, gestational age, and body mass index (BMI). Difference of
      ?PCBs level was found between normal birth and adverse birth outcomes. Neonates
      from Guiyu are exposed to high levels of PCBs; prenatal exposure to PCBs appears
      to influence neonatal health, but still needs further confirmation.

PMID- 21851984
TI  - Hard to swallow: a systematic review of deliberate foreign body ingestion.
AB  - OBJECTIVE: Deliberate foreign body ingestion (DFBI) is often impulsively driven,
      repetitive and refractory to intervention and frequently necessitates multiple
      medical interventions. As such, the frustrations among health care providers are
      great, and the financial toll on health care is significant. Nevertheless, the
      literature on DFBI is sparse, and suggestions for treatment planning and
      management are limited. The authors sought to investigate and uncover efficacious
      treatments and strategies for preventing reoccurrence in DFBI. We build on
      earlier work by offering both broad and diagnosis-specific management strategies.
      METHOD: A literature review was performed addressing the presentation, management
      and prevention of reoccurrences of DFBI. Four cases of DFBI are presented
      illustrating those psychiatric diagnoses (psychosis, malingering, obsessive
      compulsive disorder and borderline personality disorder) most frequently
      encountered in hospital practice. Both broad and specific treatment approaches
      are presented. RESULTS: Patients engaging in DFBI are best managed through a
      multidisciplinary approach, following acute medical management. Successful
      strategies for the prevention of reoccurrences of DFBI are inconclusive.
      CONCLUSION: Understanding the function of this behavior is critical in developing
      treatment for patients who engage in these dangerous, potentially life
      threatening, self-injurious behaviors. An amalgam of medical, pharmacological and
      cognitive-behavioral interventions is recommended, as is additional research.

PMID- 21851985
TI  - Specific fatigue-related items in self-rating depression scales do not bias an
      association between depression and fatigue in patients with coronary artery
      disease.
AB  - OBJECTIVE: Self-rating instruments for depression include questions targeting
      fatigue, which is a common symptom of coronary artery disease (CAD) patients. We
      evaluated if specific fatigue-related questions in self-reported instruments of
      depression bias an association between fatigue and depression in CAD patients.
      METHODS: A total of 1470 CAD patients attending cardiac rehabilitation program
      were evaluated for fatigue using the Multidimensional Fatigue Inventory (MFI-20)
      and for symptoms of depression using the depression subscale of the Hospital
      Anxiety and Depression scale (HADS-D) and the Beck Depression Inventory-II (BDI
      II). RESULTS: There was moderate correlation in MFI-20 scores vs. HADS-D scores
      and in MFI-20 scores vs. BDI-II scores, with stronger association in patients
      with less severe heart failure when compared to patients with more severe heart
      failure. Removal of questions targeting fatigue from the HADS-D and the BDI-II
      did not significantly change the association. CONCLUSIONS: Fatigue-related items
      should not be removed from the HADS-D and the BDI-II when evaluating CAD patients
      for depressive symptoms.

PMID- 21851986
TI  - Prevalence and factors associated with depressive disorders in an HIV+ rural
      patient population in southern Uganda.
AB  - BACKGROUND: Depressive disorders are estimated to occur in nearly half of HIV
      infected individuals worldwide. AIM: To examine the prevalence and cardinal
      demographic, psychosocial and clinical features associated with having any
      depressive disorder, sub-clinical depression, current and lifetime depressive
      disorders among patients with human immunodeficiency virus (HIV) in southern
      Uganda. METHODS: Five hundred HIV+ individuals were screened for depression using
      a 20 item self-reporting questionnaire (SRQ-20) and evaluated with the mini
      neuropsychiatric interview(MINI) that assessed current and lifetime depressive
      disorders. RESULTS: The prevalence estimates of any depressive disorder,
      subclinical depression, both current and lifetime major depression, and bipolar
      depression were 46.4%, 17.8%, 25% and 3.6% respectively. In comparison to non
      depressed patients, those with sub-clinical depression were less likely to have
      high levels of self-efficacy, more likely to be using ART for less than one year,
      have advanced HIV disease and current alcohol use disorders (AUD's). Those with
      both current and lifetime depressive disorders were less likely to be 85%
      adherent to antiretroviral therapy (ART), have social support and high levels of
      self-efficacy, more likely to have tuberculosis and past manic episodes. Those
      with only lifetime depressive disorders were more likely to have current AUD's
      and past manic episodes. LIMITATIONS: Information concerning exposures and
      outcomes was collected simultaneously, thus causal relationships are difficult to
      establish. CONCLUSIONS: Sub-clinical depression, major depression and bipolar
      depression are widespread among HIV patients receiving ART. Integration of mental
      health services into HIV Care is desperately needed.

PMID- 21851987
TI  - Cost-effectiveness comparisons between antidepressant treatments in depression:
      evidence from database analyses and prospective studies.
AB  - BACKGROUND: Knowledge regarding the relative cost-effectiveness of different
      antidepressants is crucial for the planning of depression treatment. However,
      there have been only a small number of reviews of such evidence and synthesizing
      economic evidence across studies is methodologically challenging. In particular,
      there have been few reviews of the methods employed in database analyses (studies
      that use data from real-world practice). METHODS: Published economic evaluations
      based on database analyses were systematically reviewed to compare antidepressant
      treatments in depression. Prospective studies of cost-effectiveness were also
      reviewed to highlight unanswered questions through comparisons between these two
      different study designs. RESULTS: Forty papers met the criteria and were
      included. A relatively large number of industry-sponsored evaluations of
      escitalopram were identified and these found escitalopram to be potentially cost
      effective in depression treatment. Evidence of cost-effectiveness differences
      between other individual SSRIs was not unequivocally established. Inconsistent
      findings further emerged concerning the cost-effectiveness of SSRIs versus TCAs
      between retrospective database analyses and prospective studies. LIMITATIONS:
      Different outcome measures and cost perspectives make it difficult to make
      comparisons across studies. CONCLUSIONS: Evidence regarding the cost
      effectiveness of different antidepressants in depression continues to accumulate.
      Beyond the efficacy or tolerability data found for newer antidepressants in
      controlled trials, further research from real-world settings is needed to examine
      the relative cost-effectiveness of different antidepressant agents.

PMID- 21851988
TI  - Relapses in recurrent depression 1 year after psychoeducational treatment: the
      role of therapist adherence and competence, and the therapeutic alliance.
AB  - Psychoeducation has proved to be an effective treatment method for the prevention
      of relapse in recurrent depression. However, little is known about the processes
      which could account for the effects of psychoeducational treatment. In this
      study, patients with recurrent depression (currently remitted) received, over a
      period of 8 months, 16 sessions of psychoeducational treatment, in order to
      prevent relapse. Therapist adherence and competence, and the therapeutic
      alliance, were investigated as predictors of reducing the recurrence risk in
      depression. Videotapes of 43 participants in a psychoeducational treatment for
      depression were analyzed, in order to evaluate therapist adherence and
      competence. Additionally, the therapeutic alliance was assessed by means of a
      questionnaire. One year after treatment, no associations were found between
      therapist adherence or competence and the risk of relapse. The patients' view of
      the therapeutic alliance was moderately associated with the time to relapse.
      However, the correlation disappeared when controlled for the number of previous
      depressive episodes. The latter was the most important predictor of time to
      relapse, explaining 15% of variance.

PMID- 21851989
TI  - Impaired discrimination between imagined and performed actions in schizophrenia.
AB  - The main aim of the present study was to investigate whether a specific type of
      source monitoring, namely self-monitoring for actions (differentiation between
      imagined and performed actions), is disrupted in schizophrenia. Persons diagnosed
      with schizophrenia (n=32) and healthy participants (n=32) were assessed with an
      action memory task. Simple actions were presented to the participants either
      verbally (short instructions) or nonverbally (icons). Some of the items required
      participants to physically perform the action whereas other actions had to be
      imagined. In the recognition phase of the study, participants were asked whether
      an action was previously displayed (verbally or nonverbally), whether it was a
      new action (not presented before), and if they had performed or imagined the
      action. In addition, participants were asked how confident they were in their
      decision. Participants in the group with schizophrenia significantly more often
      misattributed imagined actions as performed and vice versa and were more
      convinced about their wrong decision than participants in the control group.
      Patients revealed worse recognition for both verbal and nonverbal actions. In
      accordance with prior studies, we found that patients were less confident in
      their correct answers than healthy subjects. However, no enhanced confidence in
      incorrect answers was found. There was no observed significant relationship
      between source misattributions and the severity of psychopathological symptoms.
      Our findings suggest tentatively general source monitoring deficits in
      schizophrenia.

PMID- 21851990
TI  - Evidence of some strategic preservation of episodic learning in patients with
      schizophrenia.
AB  - The aim of this study was to gain a better understanding of schizophrenia
      patients' strategic use of learning time allocation during encoding, and
      determine whether they are able to use their monitoring and previous performances
      to adapt their learning behavior efficiently. Schizophrenia is considered to be a
      pathology of consciousness as well as being associated with impaired awareness of
      cognitive processes. In this study, after a learning session, individuals may
      express a Judgment of Learning (JOL), which reflects their sense of being able to
      retrieve the information later and which forms the basis for their decision
      whether or not to carry on learning. The introspective abilities of schizophrenia
      patients and subsequent strategic control of study time during the encoding of
      easy or difficult word pairs were investigated in 23 patients and 23 healthy
      comparison subjects. In spite of their memory impairment, patients were able to
      judge the difficulty of the word pairs with accuracy and adapt their learning
      time accordingly. Schizophrenia patients are sensitive to difficulty when rating
      JOLs and afterwards controlling study time. Monitoring their knowledge at the
      start helped patients to adapt their learning efficiently. These findings may be
      of value for cognitive remediation.

PMID- 21851991
TI  - Correlation of mucociliary clearance and symptomatology before and after
      adenoidectomy in children.
AB  - OBJECTIVE: The goal of this study is to better understand the role of adenoid
      hypertrophy and its impact on mucociliary clearance as it relates to the symptoms
      of chronic sinusitis in children. More specifically, the goal is to better
      understand which symptoms of chronic rhinosinusitis might be most likely to
      improve in children undergoing an adenoidectomy. METHODS: We conducted this study
      on 35 healthy children (>3 and <18 years of age), either male or female, who
      underwent adenotonsillectomy or adenoidectomy (with or without tympanostomy tube
      insertion). Eighteen patients completed pre- and postoperative surveys, with 10
      also completing the Andersen's saccharine test (AST). The nasal mucociliary
      clearance will be evaluated with the AST, in which a saccharin particle (1.5mm
      diameter) is carefully placed on the floor of the nasal cavity approximately 1cm
      behind the anterior end of the inferior turbinate. The time taken by the subjects
      from placement of particle to the perception of the sweet taste will be taken as
      mucociliary clearance time (MCT). The length of the nasal cavity is measured
      intraoperatively as the distance between the upper medial incisor and the
      inferior edge of the soft palate. From these two values nasal mucociliary
      clearance velocity (MCV) (cm/min) can be calculated and assessed. This study took
      place at an academic institution. RESULTS: Symptomatic improvement was seen in
      all categories, as measured by the mean score improvement postoperatively. The
      greatest improvements were seen in nasal obstruction (mean=2.67 points +/- .59)
      on the symptom survey, and emotional distress (mean=2.56 +/- .47) on the SN5
      survey. Quality of life improved by a mean=2.61 +/- .49. Both MCT and MCV
      improved postoperatively (mean 3.64 min +/- .84 and mean 1.96 cm/min +/-.90,
      respectively). CONCLUSIONS: We believe this study has the potential to provide
      otolaryngologists across the country with a benchmark to communicate the specific
      symptomatic benefits from adenoidectomy.

PMID- 21851993
TI  - High-density lipoprotein-dependent effects of statins on the risk of coronary
      heart disease deaths and events.

PMID- 21851994
TI  - Total mortality among levothyroxine-treated women with atrial fibrillation in
      Swedish primary health care.

PMID- 21851995
TI  - Early enhancement on contrast-enhanced cardiovascular magnetic resonance imaging
      in takotsubo cardiomyopathy: two cases.

PMID- 21851992
TI  - A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP.
AB  - According to the Hebb rule, the change in the strength of a synapse depends only
      on the local interaction of presynaptic and postsynaptic events. Studies at many
      types of synapses indicate that the early phase of long-term potentiation (LTP)
      has Hebbian properties. However, it is now clear that the Hebb rule does not
      account for late LTP; this requires an additional signal that is non-local. For
      novel information and motivational events such as rewards this signal at
      hippocampal CA1 synapses is mediated by the neuromodulator, dopamine. In this
      Review we discuss recent experimental findings that support the view that this
      'neoHebbian' framework can account for memory behavior in a variety of learning
      situations.

PMID- 21851996
TI  - Benefit, rather than safety, of cilostazol for long-term mortality in patients
      undergoing percutaneous coronary intervention: a meta-analysis of randomized
      trials.

PMID- 21851997
TI  - Embolization of hydrophilic coating material to small intracardial arteries after
      multiple percutaneous transluminal angioplasty procedures.

PMID- 21851998
TI  - Endothelial dysfunction in type 2 diabetic patients with normal coronary
      arteries: a digital reactive hyperemia study.
AB  - BACKGROUND: To assess endothelial function (EF) in type 2 diabetic patients with
      angiographically normal coronaries compared to diabetic patients with obstructive
      coronary artery disease (CAD) and to non-diabetic patients, with and without CAD.
      METHODS: One hundred eighty-three patients undergoing coronary angiography were
      divided in: group 1 with diabetes mellitus (DM) and CAD (n = 58); group 2 with DM
      without CAD (n = 58); group 3 with CAD without DM (n = 31) and group 4 without
      CAD and DM (n = 36). EF was assessed by reactive hyperemia index (RHI) using a
      fingertip peripheral arterial tonometry and compared to values obtained in 20
      healthy volunteers. RESULTS: RHI was significantly lower in patients with DM
      compared to patients without DM (1.69 +/- 0.38 vs 1.84 +/- 0.44; p = 0.019). RHI
      was comparable among groups 1, 2 and 3, each value being significantly lower
      compared to group 4 (2 +/- 0.44; p<0.001 vs group 1; p<0.005 vs group 2; p<0.002
      vs group 3). At multivariate analysis DM and CAD were significant predictors of
      endothelial dysfunction (ED) (OR = 2.29; p = 0.012; OR = 2.76; p = 0.001,
      respectively), whereas diabetic patients (n = 116) CAD and glycated haemoglobin
      (HbA1c) were independent significant predictors of ED (OR = 3.05; p = 0.009; OR =
      1.96; p = 0.004, respectively). Diabetic patients with ED (n = 67) had higher
      levels of HbA1c than diabetic patients with normal endothelial function (7.35 +/-
      0.97 vs 6.87 +/- 0.90; p = 0.008) and RHI inversely correlated to HbA1c (p =
      0.02; r = -0.210). CONCLUSIONS: Diabetic patients with and without CAD show
      significantly impaired peripheral vascular function compared to non-diabetic
      patients without CAD. ED in diabetic patients without CAD is comparable to that
      of patients with CAD but without DM. HbA1c is a weak independent predictor of ED.

PMID- 21851999
TI  - Impact of applying NICE guidance for the assessment of stable chest pain in rapid
      access chest pain clinics in a DGH: a service evaluation.

PMID- 21852000
TI  - Cardiac determinants of impaired exercise performance in patients with type 2
      diabetes mellitus.

PMID- 21852001
TI  - Meta-analysis of P wave character as predictor of atrial fibrillation after
      coronary artery bypass grafting.

PMID- 21852002
TI  - Without a quadripolar left ventricular lead you don't succeed: a challenging case
      of phrenic nerve stimulation.

PMID- 21852003
TI  - Stem cells transplantation combined with long-term mechanical circulatory support
      enhances myocardial viability in end-stage ischemic cardiomyopathy.

PMID- 21852004
TI  - Ventricular repolarization during uni and biventricular pacing in normal
      subjects.
AB  - BACKGROUND: The cardiac depolarization-repolarization process (D-REPP) may differ
      among various modes of cardiac pacing depending on the paced chamber(s) and lead
      position. We intended to assess the effect of different modes of cardiac pacing
      (left, right and biventricular) on the D-REPP as expressed in QRS, QT, peak-to
      end of the T wave (PETW) and PETW/QT intervals and their dispersion. These
      intervals were compared during pacing and sinus rhythm. METHODS: We studied 31
      patients without structural heart disease and with normal ventricular function
      who underwent right, left and biventricular pacing. Simultaneous 12-leads were
      recorded and electronic calipers were used for measurement of the QRS, QT,
      corrected QT (cQT), PETW, and PETW/QT ratio. RESULTS: cQT duration, PETW,
      standard deviation of the PETW, PETW/QT, and QRS duration were shorter during
      sinus rhythm. Isolated stimulation of the right or the left ventricle produced a
      similar increase in all the intervals and did not display significant differences
      in terms of cQT duration, PETW, PETW/QT, or QRS duration. Biventricular pacing
      produced a significant increase in cQT, QRS, PETW and PETW/QT, but these values
      were shorter than those obtained during isolated right or left ventricular
      stimulation. CONCLUSION: In subjects without structural heart disease, cardiac
      pacing produces a significant increase of the D-REPP. No differences were found
      when comparing right or left univentricular pacing. Biventricular stimulation
      induces less perturbation of the D-REPP.

PMID- 21852005
TI  - Chronic renal impairment in patients with Chagas cardiomyopathy with chronic
      systolic heart failure: prevalence and prognostic significance.

PMID- 21852006
TI  - Warfarin resistance and caffeine containing beverages.

PMID- 21852007
TI  - The importance of location in contact networks: Describing early epidemic spread
      using spatial social network analysis.
AB  - This paper explores methods for describing the dynamics of early epidemic spread
      and the clustering of infected cases in space and time when an underlying contact
      network structure is influencing disease spread. A novel method of describing an
      epidemic is presented that applies social network analysis to characterise the
      importance of both spatial location and contact network position. This method
      enables the development of a model of how these clusters formed, incorporating
      spatial clustering and contact network topology. Based on data from the first 30
      days of the 2007 equine influenza outbreak in Australia, clusters of infected
      premises (IPs) were identified and delineated using social network analysis to
      integrate contact-tracing and spatial relationships. Clusters identified by this
      approach were compared to those detected using the space-time scan statistic to
      analyse the same data. To further investigate the importance of network and
      spatial location in epidemic spread, kriging by date of onset of clinical signs
      was used to model the spatio-temporal spread without reference to underlying
      contact network structure. Leave-one-out cross-validation was used to derive a
      summary estimate of the accuracy of the kriged surface. Observations poorly
      explained by the kriged surface were identified, and their position within the
      contact network was explored to determine if they could be better explained
      through analysis of the underlying contact network. The contact network was found
      to lie at the core of a combined network model of spread, with infected horse
      movements connecting spatial clusters of infected premises. Kriging was imprecise
      in describing the pattern of spread during this early phase of the outbreak
      (explaining only 13% of the variation in date of onset of IPs), because early
      dissemination was dominated by network-based spread. Combined analysis of spatial
      and contact network data demonstrated that over the first 30 days of this
      outbreak local spread emanated outwards from the small number of infected
      premises in the contact network, up to a distance of around 15km. Consequently,
      when a contact network structure underlies epidemic spread, we recommend applying
      a method of spatial analysis that incorporates the network component of disease
      spread. Linking the spatial and network analysis of epidemics facilitates
      inference of the methods of disease transmission, providing a description of the
      sequence of spatial cluster formation.

PMID- 21852008
TI  - Epidemiological aspects and financial impact of lumpy skin disease in Ethiopia.
AB  - The financial cost of clinical Lumpy Skin Disease (LSD) and the financial benefit
      of its control through vaccination were studied based on questionnaire survey in
      Oromia region of Ethiopia from the perspective of livestock farmers. Production
      loss impacts for local zebu cattle were compared with those of Holstein Friesian
      (HF)/crossbred cattle in the study area. Annual cumulative incidence of LSD
      infection in HF/crossbred and local zebu cattle were 33.93% (95% CI: 30.92-36.94)
      and 13.41% (95% CI: 12.6-14.25) respectively and significantly different
      (p<0.05). Annual mortality was also significantly higher in HF/crossbred 7.43%
      (95% CI: 5.76-9.10) than in local zebu cattle 1.25% (95% CI: 0.98-1.52). The
      annual financial cost was calculated as the sum of the average production losses
      due to morbidity and mortality arising from milk loss, beef loss, traction power
      loss, and treatment and vaccination costs at the herd level. The financial cost
      in infected herds was estimated to be USD 6.43 (5.12-8) per head for local zebu
      and USD 58 (42-73) per head for HF/crossbred cattle. A partial budget analysis
      was used to estimate the financial benefit of an annual vaccination program in
      both the local zebu and HF/crossbred cattle farming systems. The marginal rate of
      return (MRR) gained from this control intervention was estimated to be 34 (3400%)
      and the net benefit per head was USD 1 for local zebu and USD 19 for HF/crossbred
      cattle. Vaccination thus enabled financial costs due to LSD to be reduced by 17%
      per head in local zebu herds and 31% per head in HF/crossbred herds. These
      results could provide guidance to producers and the government in their endeavors
      to control the disease.

PMID- 21852009
TI  - Happy house: spousal weight and individual well-being.
AB  - We use life satisfaction and Body Mass Index (BMI) information from three waves
      of the GSOEP to test for social interactions in BMI between spouses. Social
      interactions require that the cross-partial effect of partner's weight and own
      weight in the utility function be positive. Using life satisfaction as a utility
      proxy, semi-parametric regressions show that the correlation between satisfaction
      and own BMI is initially positive, but turns negative after some threshold.
      Critically, this latter threshold increases with partner's BMI when the
      individual is overweight. The negative well-being impact of own BMI is thus lower
      when the individual's partner is heavier, which is consistent with social
      contagion effects in weight. However, this relationship may also reflect
      selection on the marriage market or omitted variables, and it is difficult to
      think of convincing instruments that would allow causality to be clearly
      established.

PMID- 21852010
TI  - Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a
      prospective randomized controlled multi-center trial.
AB  - BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) presents a high risk
      breast cancer that lacks the benefit from hormone treatment, chemotherapy is the
      main strategy even though it exists in poor prognosis. Use of adjuvant radiation
      therapy, which significantly decreases breast cancer mortality, has not been well
      described among poor TNBC women. The aim of this study was to evaluate whether
      the combination of chemotherapy and radiotherapy could significantly increase
      survival outcomes in TNBC women after mastectomy. PATIENTS AND METHODS: A
      prospective randomized controlled multi-center study was performed between
      February 2001 and February 2006 and comprised 681 women with triple-negative
      stage I-II breast cancer received mastectomy, of them, 315 cases received
      systemic chemotherapy alone, 366 patients received radiation after the course of
      chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were
      estimated. Simultaneously local and systemic toxicity were observed. RESULTS:
      After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6%
      for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone,
      respectively, with significant difference between the two groups (HR 0.77 [95% CI
      0.72, 0.98]; P=0.02). Five-year OS significantly improved in adjuvant
      chemotherapy plus radiation group compared with chemotherapy alone (90.4% and
      78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P=0.03). No severe toxicity was reported.
      CONCLUSIONS: Patients received standard adjuvant chemotherapy plus radiation
      therapy was more effective than chemotherapy alone in women with triple-negative
      early-stage breast cancer after mastectomy.

PMID- 21852011
TI  - Survivin inhibition and DNA double-strand break repair: a molecular mechanism to
      overcome radioresistance in glioblastoma.
AB  - BACKGROUND AND PURPOSE: Gliomas display prime examples of ionizing radiation (IR)
      resistant tumors. The IAP Survivin is reported to be critically involved in
      radiation resistance by anti-apoptotic and by caspase-independent mechanisms. The
      present study aimed to elucidate an interrelationship between Survivin's cellular
      localization and DNA damage repair in glioma cells. MATERIAL AND METHODS:
      Cellular distribution and nuclear complex formation were assayed by
      immunoblotting, immunofluorescence staining and co-immunoprecipitation of
      Survivin bound proteins in LN229 glioblastoma cells. Apoptosis induction,
      survival and DNA repair following IR were assayed by means of caspase3/7
      activity, clonogenic assay, gamma-H2AX/53BP1 foci formation, single cell gel
      electrophoresis assay, and DNA-PKcs kinase assay in the presence of Survivin
      siRNA or over expression of Survivin-GFP. RESULTS: Following irradiation, we
      observed a nuclear accumulation and a direct interrelationship between Survivin,
      MDC1, gamma-H2AX, 53BP1 and DNA-PKcs, which was confirmed by immunofluorescence
      co-localization. Survivin downregulation by siRNA resulted in an increased
      apoptotic fraction, decreased clonogenic survival and increased DNA-damage, as
      demonstrated by higher amount of DNA breaks and an increased amount of gamma
      H2AX/53BP1 foci post irradiation. Furthermore, we detected in Survivin-depleted
      LN229 cells a hampered S2056 (auto)phosphorylation and a significantly decreased
      DNA-PKcs kinase activity. CONCLUSION: Nuclear accumulation of Survivin and
      interaction with components of the DNA-double-strand break (DSB) repair machinery
      indicates Survivin to regulate DSB damage repair that leads to a significant
      improvement of survival of LN229 glioblastoma cells.

PMID- 21852012
TI  - Motor timing deficits in children with Attention-Deficit/Hyperactivity disorder.
AB  - Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are thought to have
      fundamental deficits in the allocation of attention for information processing.
      Furthermore, it is believed that these children possess a fundamental difficulty
      in motoric timing, an assertion that has been explored recently in adults and
      children. In the present study we extend this recent work by fully exploring the
      classic Wing and Kristofferson (1973) analysis of timing with typically
      developing children (n=24) and children with ADHD (n=27). We provide clear
      evidence that not only do children with ADHD have an overall timing deficit, they
      also time less consistently when using a similar strategy to typically developing
      children. The use of the Wing and Kristofferson approach to timing, we argue,
      will result in the discovery of robust ADHD-related timing differences across a
      variety of situations.

PMID- 21852013
TI  - Intergenerational anticipation of disease onset in people with multiple
      autoimmune syndrome.
AB  - We compared the intergenerational variations of the clinical phenotype between 30
      patients affected with multiple autoimmune syndrome (MAS) and their affected
      first- and second-degree relatives. Mean age at onset was always significantly
      higher in the previous generation than in probands for all the considered
      diseases.

PMID- 21852014
TI  - Is HbA1c a valid and feasible tool for the diagnosis of diabetes?

PMID- 21852015
TI  - Socio-demographic patient profiles and hospital efficiency: does patient mix
      affect a hospital's ability to perform?
AB  - This study investigates whether inclusion of patient profiles impacts on the
      inferences drawn from measuring performance using patient level data. Performance
      is in this setting defined by resources used in treating patients in a given
      diagnose related group where use of resources is approximated by length of stay
      (LOS). The analysis is based on Danish registry data from 2006. Patient data
      include registry data on income, employment status and information on whether the
      patient receives benefits or lives alone. Considerable variation in the socio
      demographic characteristics of patients across Danish hospitals was observed, and
      some patient characteristics were shown to drive the need for longer hospital
      stays beyond what is captured in DRG scores. Ranking of hospitals based on
      observed versus expected LOS remained largely unaffected when controlling for
      patient characteristics, suggesting that variation in LOS across hospitals is
      mainly driven by other factors than patients' socio-demographic characteristics.
      Nevertheless, the results of this study indicate that the current Danish
      remuneration system discriminates hospitals that more often serve older patients
      and patients with a less developed social network. These hospitals tend to have a
      reduced turnover of patients and their ability to generate revenue is therefore
      constrained.

PMID- 21852016
TI  - HiL simulation in biomechanics: a new approach for testing total joint
      replacements.
AB  - Instability of artificial joints is still one of the most prevalent reasons for
      revision surgery caused by various influencing factors. In order to investigate
      instability mechanisms such as dislocation under reproducible, physiologically
      realistic boundary conditions, a novel test approach is introduced by means of a
      hardware-in-the-loop (HiL) simulation involving a highly flexible mechatronic
      test system. In this work, the underlying concept and implementation of all
      required units is presented enabling comparable investigations of different total
      hip and knee replacements, respectively. The HiL joint simulator consists of two
      units: a physical setup composed of a six-axes industrial robot and a numerical
      multibody model running in real-time. Within the multibody model, the anatomical
      environment of the considered joint is represented such that the soft tissue
      response is accounted for during an instability event. Hence, the robot loads and
      moves the real implant components according to the information provided by the
      multibody model while transferring back the position and resisting moment
      recorded. Functionality of the simulator is proved by testing the underlying
      control principles, and verified by reproducing the dislocation process of a
      standard total hip replacement. HiL simulations provide a new biomechanical
      testing tool for analyzing different joint replacement systems with respect to
      their instability behavior under realistic movements and physiological load
      conditions.

PMID- 21852017
TI  - Recovery of marine animal populations and ecosystems.
AB  - Many marine populations and ecosystems have experienced strong historical
      depletions, yet reports of recoveries are increasing. Here, we review the growing
      research on marine recoveries to reveal how common recovery is, its magnitude,
      timescale and major drivers. Overall, 10-50% of depleted populations and
      ecosystems show some recovery, but rarely to former levels of abundance. In
      addition, recovery can take many decades for long-lived species and complex
      ecosystems. Major drivers of recovery include the reduction of human impacts,
      especially exploitation, habitat loss and pollution, combined with favorable life
      history and environmental conditions. Awareness, legal protection and enforcement
      of management plans are also crucial. Learning from historical recovery successes
      and failures is essential for implementing realistic conservation goals and
      promising management strategies.

PMID- 21852018
TI  - Factor H as a regulator of the classical pathway activation.
AB  - C1q, the first subcomponent of the classical pathway, is a charge pattern
      recognition molecule that binds a diverse range of self, non-self and altered
      self ligands, leading to pro-inflammatory complement activation. Although
      complement is required for tissue homeostasis as well as defence against
      pathogens, exaggerated complement activation can be damaging to the tissue.
      Therefore, a fine balance between complement activation and inhibition is
      necessary. We have recently found that factor H, a polyanion recognition molecule
      and soluble regulator of alternative pathway activation in blood and on cell
      surfaces, can directly compete with C1q in binding to anionic phospholipids
      (cardiolipin), lipid A and Escherichia coli (three known activators of the
      classical pathway) and acts as a direct down regulator of the complement
      classical pathway. This ability of factor H to dampen classical pathway
      activation is distinct from its role as an alternative pathway down-regulator.
      Thus, by directly competing for specific C1q ligands (exogenous as well as
      endogenous), factor H is likely to be involved in fine-tuning and balancing the
      C1q-driven inflammatory processes in autoimmunity and infection. However, in the
      case of apoptotic cells, C1q-mediated enhancement of uptake/adhesion of the
      apoptotic cells by monocytes was reduced by factor H. Thus, factor H may be
      important in controlling the inflammation, which might arise from C1q deposition
      on apoptotic cells.

PMID- 21852019
TI  - Is complement a culprit in infection-induced forms of haemolytic uraemic
      syndrome?
AB  - Haemolytic uraemic syndrome (HUS) accounts for the most common cause of childhood
      acute renal failure. Characterized by the classical triad of a microangiopathic
      haemolytic anaemia, thrombocytopaenia and acute renal failure, HUS occurs as a
      result of Shiga-toxin producing microbes in 90% of cases. The remaining 10% of
      cases represent a heterogeneous subgroup in which inherited and acquired forms of
      complement dysregulation have been described in up to 60%. Emerging evidence
      suggests that microbes associated with HUS exhibit interaction with the
      complement system. With the advent of improved genetic diagnosis, it is likely
      that certain cases of infection-induced HUS may be attributed to underlying
      defects in complement components. This review summarises the interplay between
      complement and infection in the pathogenesis of HUS.

PMID- 21852020
TI  - Variation in complement component C1 inhibitor in age-related macular
      degeneration.
AB  - This study assessed variation in plasma levels of the complement regulatorC1
      inhibitor (C1inh) in patients with age related macular degeneration (AMD) and
      controls. Plasma from391 AMD cases and 370 controls was assayed by rate
      nephelometry to determine C1inh protein levels. Protein levels were analysed for
      relationships with age, gender, smoking, AMD disease status and genetic variation
      in the SERPING1 gene, which encodes C1inh, using a multivariate analysis. t-Tests
      show a significant difference in C1inh levels in AMD cases compared with controls
      (p=2.340E-6), smokers compared to non-smokers (p=1.022E-4) and females compared
      to males (p=1.661E-7). Multivariate analysis shows that after accounting for
      gender and smoking AMD status remained significant. Age was included in the model
      but was not significant. Including genetic variation in the model shows that one
      significant SNP (rs2649663) 5' of the SERPING1 gene is associated with C1inh
      levels though this SNP is not associated with AMD. This suggests that genetic
      variation in the promoter region of the SERPING1 gene may influence expression of
      the gene.

PMID- 21852021
TI  - Chemical labelling of active serum thioester proteins for quantification.
AB  - The complement serum proteins C3 and C4 and the protease inhibitor alpha-2
      macroglobulin are all members of the C3/alpha-2M thioester protein family, an
      evolutionarily ancient and conserved family that contains an intrachain thioester
      bond. The chemistry of the thioester bond is a key to the function of the
      thioester proteins. All these proteins function by covalently linking to their
      target by acyl transfer of the protein via the thioester moiety. We show that the
      signature thioester bond can be targeted with nucleophiles linked to a
      bioreporter molecule, site-specifically modifying the whole, intact thioester
      protein. Conditions were optimised to label selectively and efficiently pull-down
      unprocessed thioester-containing proteins from serum. We demonstrated pull-down
      of full-length C3, alpha-2M and C4 from sera in high salt, using a biotinylated
      nucleophile and streptavidin-coated resin, confirmed by MALDI-TOF MS
      identification of the gel bands. The potential for the development of a
      quantitative method for measuring active C3 in serum was investigated in patient
      sera pre and post operation. Quantifying active C3 in clinical assays using
      current methods is difficult. Methods based on antibody detection (e.g.
      nephelometry) do not distinguish between active C3 and inactive breakdown
      products. C3-specific haemolytic assays can be used, but these require use of
      relatively unstable reagents. The current work represents a promising robust,
      enzyme- and antibody-free chemical method for detecting active thioester proteins
      in blood, plasma or serum.

PMID- 21852022
TI  - Novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish
      family with ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder.
      About 10% of ALS cases are familial (FALS) and the genetic defect is known only
      in approximately 20%-30% of these cases. The most common genetic cause of ALS is
      SOD1 (superoxide dismutase 1) mutation. Very recently, mutations of the
      optineurin gene (OPTN), which is involved in open-angle glaucoma, were identified
      in 3 Japanese patients/families with ALS, and subsequently in a few FALS patients
      of European descent. We found a heterozygous nonsense mutation (c.493C>T,
      p.Gln165X, exon 6) in the OPTN gene in a Danish patient with ALS, and the
      mutation segregated from his affected father. The p.Gln165X mutation could not be
      detected in 1070 healthy Danish controls, in 1000 Danish individuals with
      metabolic phenotypes or in 64 sporadic ALS (SALS) cases. The p.Gln165X mutation
      described in this study is the first mutation reported in a Danish family and is
      likely involved in disease pathogenesis. Until now, only few OPTN mutations have
      been associated with ALS. As the underlying genetic defect is known only in
      approximately 20%-30% of FALS families, further screening of these cases is
      necessary for establishing the contribution of OPTN mutations in disease
      pathogenesis.

PMID- 21852023
TI  - Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase
      inhibitory and anticancer activities.
AB  - KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2
      morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src
      substrate binding site inhibitor. To understand better the role of pyridine ring
      and N-benzylsubstitution in KX2-391 and establish the structure-activity
      relationship, a number of N-benzyl substituted (((2
      morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole
      instead of pyridine were synthesized and evaluated for Src kinase inhibitory
      activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c
      Src kinase with GI(50) values of 1.34 MUM and 2.30 MUM in NIH3T3/c-Src527F and
      SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated
      for inhibition of cell proliferation of human colon carcinoma (HT-29), breast
      carcinoma (BT-20), and leukemia (CCRF-CEM) cells. 4-Fluorobenzylthiazolyl
      derivative 8b exhibited 64-71% inhibition in the cell proliferation of BT-20 and
      CCRF cells at concentration of 50 MUM.

PMID- 21852024
TI  - [Training in internal medicine: the young internists' point of view].
AB  - In France, internal medicine is a speciality obtained after 5 years of
      theoretical and practical training, often completed by additional years. The last
      version of the official training program was released in 2004 and was
      characterised by its polyvalence. After the reform of medical studies was
      announced, the French young internists group decided to carry out a survey in
      order to know the vision of the young internist about their initial theoretical
      and practical training. This survey was done online using a questionnaire from
      February 10th to April 8th, 2010. One hundred and twenty-three young internists
      under training completed the questionnaire. The results showed that a high number
      of trainees chose a subspeciality and took a complementary training afterwards.
      About 63% of them would rather have more theoretical training through lectures
      (72%) and oral presentations (58%). Eighty-eight per cent of young internists
      would rather have a national frame of reference with a common training program.
      According to 73% of the young internists who completed the survey, the practical
      training is adapted but 95% of them would like to be given the opportunity to
      have some consultation during their initial training. Seventy-nine per cent of
      the young internists seem to be interested in the clinical research but most of
      them (89%) think to be not well trained enough to do it.

PMID- 21852025
TI  - [Progressive neuropathy in a 60-year-old man].

PMID- 21852026
TI  - What predicts the selection of nursing as a career choice in 5th and 6th year
      school students?
AB  - Demand for nursing care, and nurses, is growing in the United Kingdom given an
      increasingly ageing patient population with long-term co-morbidities. An ageing
      nursing workforce and fewer school leavers entering nursing are key barriers to
      student nurse recruitment. This paper aims to identify the socio-demographic and
      correlates nursing as a career choice in 5th and 6th year school students. This
      cross-sectional descriptive study gathered self-administered questionnaires from
      a total cohort of 5th and 6th year school students (n=1059) in one educational
      authority in Scotland. A response rate of 100% was achieved, with 702 students
      expressing a career choice. Some 71.7% (n=503) of students providing a full data
      set would never consider nursing, even if they obtained poor grades. Only 28.3%
      (n=199) would ever consider nursing. Students cited nursing as a career choice if
      they were female, of average to below average academic ability/achievement,
      expressed a positive attitude to nursing as a degree subject which was shared by
      their career guidance teacher. Each additional higher reduced the likelihood of
      nursing as a career choice by 22%. Nursing is an unpopular career choice amongst
      school students. Strategies are required to improve the occupational image of
      nursing in secondary education.

PMID- 21852027
TI  - Adverse effects of fullerenes (nC60) spiked to sediments on Lumbriculus
      variegatus (Oligochaeta).
AB  - Effects of fullerene-spiked sediment on a benthic organism, Lumbriculus
      variegatus (Oligochaeta), were investigated. Survival, growth, reproduction, and
      feeding rates were measured to assess possible adverse effects of fullerene
      agglomerates produced by water stirring and then spiked to a natural sediment. L.
      variegatus were exposed to 10 and 50 mg fullerenes/kg sediment dry mass for 28 d.
      These concentrations did not impact worm survival or reproduction compared to the
      control. Feeding activities were slightly decreased for both concentrations
      indicating fullerenes' disruptive effect on feeding. Depuration efficiency
      decreased in the high concentration only. Electron and light microscopy and
      extraction of the worm fecal pellets revealed fullerene agglomerates in the gut
      tract but not absorption into gut epithelial cells. Micrographs also indicated
      that 16% of the epidermal cuticle fibers of the worms were not present in the 50
      mg/kg exposures, which may make worms susceptible to other contaminants.

PMID- 21852028
TI  - The effect of food insecurity on mental health: panel evidence from rural Zambia.
AB  - A growing number of studies show support for a positive association between food
      insecurity and poor mental health in developing countries. Few of these studies,
      however, explore the relationship statistically employing longitudinal data. This
      study combines ethnography with randomly sampled household-level panel data (two
      waves) collected in 2009 to examine the association between food insecurity and
      mental health in rural Zambia. Mental health was measured using the Self
      Reporting Questionnaire and food insecurity was assessed utilizing a modified 7
      item scale based on local coping strategies used during food shortages. A
      multilevel linear regression model was employed with repeated measures nested
      within individuals (N = 280 observations) living in 81 households nested within
      16 villages. Regression results confirm the postulated positive association
      between poor mental health and food insecurity. Food insecurity during the dry
      season, the time of year in rural Zambia when many households are typically food
      secure, had a subsequent greater effect on mental health than food insecurity
      during the rainy season. The difference in the effect was statistically
      significant at the five-percent level. In a country where mental health care
      resources are severely lacking, policy and applied efforts aimed at improving
      access to key agricultural resources, thereby increasing agricultural output,
      could potentially produce beneficial mental health outcomes.

PMID- 21852029
TI  - Individual, study, and neighborhood level characteristics associated with peer
      recruitment of young illicit drug users in New York City: optimizing respondent
      driven sampling.
AB  - Recruiting a representative sample using respondent driven sampling (RDS) relies
      on successful peer recruitment. While prior studies have identified individual
      level characteristics associated with peer recruitment, study- and neighborhood
      level factors may also influence peer recruitment. This analysis aimed to
      identify individual-, study-, and neighborhood-level factors associated with RDS
      peer recruitment. 390 young adult (18-40 years) heroin, crack and/or cocaine
      users in New York City (NYC) were recruited via RDS into a cohort study aiming to
      identify social risk factors for transitioning from non-injection to injection
      drug use (2006-2009). Individual-level baseline characteristics (demographics,
      drug use, and network characteristics) and study factors (number of recruitment
      coupons received and participant attendance at RDS training sessions (RDST) on
      peer recruitment) were ascertained. Aggregate measures of neighborhood attitudes
      about drug use, drug users, and HIV were obtained from a separate anonymous NYC
      resident random-digit-dialing survey (2002) and linked with baseline data by zip
      code. Descriptive statistics and multilevel modeling were used to identify
      factors associated with peer recruitment. After adjustment, recruiting each
      additional eligible peer recruit was associated with receiving additional
      recruitment coupons, RDST attendance, and a greater proportion of community
      residents in one's recruitment neighborhood believing that clean needles should
      be made available to IDUs; heroin use was negatively associated with recruiting
      additional eligible peers. After adjustment, recruiting each additional peer
      (regardless of eligibility) was associated with receiving additional recruitment
      coupons and RDST attendance. Our data highlight the importance of neighborhood
      factors and suggest that RDS may not be as effective in areas characterized by
      negative attitudes about drug use. Group-facilitated recruitment training
      sessions may help counter negative social norms when implementing RDS in drug
      user studies.

PMID- 21852030
TI  - A multilevel intervention for HIV-affected families in China: Together for
      Empowerment Activities (TEA).
AB  - This article analyzes the efficacy of the Together for Empowerment Activities
      (TEA) intervention in decreasing depressive symptoms and improving social support
      for persons living with HIV (PLH) and their family members. A total of 79
      families, consisting of 88 PLH and 79 family members, were recruited from Anhui
      province, China, and randomized to the TEA intervention (n = 38) or a control
      condition (n = 41). The intervention was delivered at three levels: 1) TEA
      Gathering (small group for PLH and family members); 2) TEA Time (home-based
      family activities with children that accompany each TEA Gathering); and 3) TEA
      Garden (community events that build social integration). Face-to-face interviews
      were administered at baseline, 3, and 6 months. Mixed-effects regression models
      and kernel density estimation were used for data analysis. PLH and their family
      members in the intervention reported significant improvements in depressive
      symptoms, social support, and family functioning at the 3-month and 6-month
      follow-up assessments compared to those in the control condition. Heterogeneous
      intervention effects on social support and family functioning were indicated at
      the 6-month follow-up. The intervention could have various effect patterns for
      different subgroups within the intervention condition. This study provides
      preliminary data to support the feasibility and efficacy of a multilevel
      intervention.

PMID- 21852031
TI  - Changes in clinical, pulmonary function, quality of life and costs in a cohort of
      asthmatic patients followed for 10 years.
AB  - Few studies have comprehensively assessed the evolution asthma disease in recent
      years. OBJECTIVES: To determine changes in morbidity, lung function and quality
      of life and to establish the impact in terms of cost in a cohort of patients with
      asthma. METHODS: Prospective, descriptive and realistic study that included 220
      asthma patients evaluated 10 years after their inclusion (1994-2004). For all the
      patients, data for symptoms, lung function, quality of life and financial cost
      were collected. RESULTS: There was a decrease in the frequency of health service
      visits, including: emergency room visits for asthma exacerbations, 0.3 (0.9)
      versus 0.6 (1) visits per patient per year (P=.003); a reduction in the severity
      of the disease, with a greater proportion of patients with mild asthma, 121
      (54.8%) versus 94 (42.7%) (P=.001); a decrease (improvement in quality of life)
      in the total SGRQ, 30.1 (16.5) versus 37 (19.6) (P<.001); and reduced total
      costs, 1,464? (3,415.8) compared to 2,267? (4.174) per patient/year (P<.001),
      mainly due to indirect costs, 617.50? (2855.9) compared to 1,320.10? (3,685.3)
      per patient/year (P=.001). When assessing the changes observed according to
      asthma severity, no differences were observed between groups. CONCLUSIONS: The
      evolution of the morbidity and quality of life of asthma patients between 1994
      and 2004 are clearly favorable. This improvement provided a significant reduction
      in the total costs of disease treatment.

PMID- 21852032
TI  - Dynamic floodplain vegetation model development for the Kootenai River, USA.
AB  - The Kootenai River floodplain in Idaho, USA, is nearly disconnected from its main
      channel due to levee construction and the operation of Libby Dam since 1972. The
      decreases in flood frequency and magnitude combined with the river modification
      have changed the physical processes and the dynamics of floodplain vegetation.
      This research describes the concept, methodologies and simulated results of the
      rule-based dynamic floodplain vegetation model "CASiMiR-vegetation" that is used
      to simulate the effect of hydrological alteration on vegetation dynamics. The
      vegetation dynamics are simulated based on existing theory but adapted to
      observed field data on the Kootenai River. The model simulates the changing
      vegetation patterns on an annual basis from an initial condition based on
      spatially distributed physical parameters such as shear stress, flood duration
      and height-over-base flow level. The model was calibrated and the robustness of
      the model was analyzed. The hydrodynamic (HD) models were used to simulate
      relevant physical processes representing historic, pre-dam, and post-dam
      conditions from different representative hydrographs. The general concept of the
      vegetation model is that a vegetation community will be recycled if the magnitude
      of a relevant physical parameter is greater than the threshold value for specific
      vegetation; otherwise, succession will take place toward maturation stage. The
      overall accuracy and agreement Kappa between simulated and field observed maps
      were low considering individual vegetation types in both calibration and
      validation areas. Overall accuracy (42% and 58%) and agreement between maps (0.18
      and 0.27) increased notably when individual vegetation types were merged into
      vegetation phases in both calibration and validation areas, respectively. The
      area balance approach was used to analyze the proportion of area occupied by
      different vegetation phases in the simulated and observed map. The result showed
      the impact of the river modification and hydrological alteration on the
      floodplain vegetation. The spatially distributed vegetation model developed in
      this study is a step forward in modeling riparian vegetation succession and can
      be used for operational loss assessment, and river and floodplain restoration
      projects.

PMID- 21852033
TI  - Robot-assisted radical cystectomy with intracorporeal urinary diversion in
      patients with transitional cell carcinoma of the bladder.
AB  - BACKGROUND: Robot-assisted radical cystectomy (RARC) may reduce morbidity after
      cystectomy. Descriptions of the surgical techniques of RARC with intracorporeal
      orthotopic neobladder or ileal conduit are sparse and oncologic and functional
      outcome data have not been reported. OBJECTIVE: We present our technique with
      RARC and intracorporeal urinary diversion (neobladder or ileal conduit) and
      present oncologic and functional outcomes, as well as complication rates. DESIGN,
      SETTING, AND PARTICIPANTS: Single-hospital institution case-series from 2004 to
      2009 including 45 selected patients (38 male, 7 female) with high-grade and/or
      muscle-invasive urothelial cancer of the bladder. SURGICAL PROCEDURE: We
      performed RARC; pelvic lymph node dissection using three different templates; and
      a totally intracorporeal urinary diversion, either orthotopic neobladder (n=36)
      or ileal conduit (n=9). MEASUREMENTS: Perioperative variables, pathology data,
      early and late complication rates, urinary continence, potency, and cancer
      specific survival were evaluated as outcome measures. RESULTS AND LIMITATIONS:
      Median patient age, operative time, estimated blood loss, and lymph node yield
      were 62 yr (range: 37-79), 477 min (range: 325-760), 550 ml (range: 200-2200),
      and 19 (range: 10-52), respectively. Nine patients were diagnosed with positive
      lymph nodes. Surgical margins were clear in all but one patient. Early
      complications occurred in 18 patients (40%). Median postoperative stay was 9 d
      (range: 4-78), and median postoperative follow-up time was 25 mo. Four patients
      died due to metastatic disease. The study is limited by a relative small sample
      size and no comparative group. CONCLUSIONS: RARC with totally intracorporeal
      urinary diversion is technically feasible with good intermediate-term oncologic
      results. This is a nonrandomised study including a limited number of patients
      with a restricted follow-up time, however, and so precautions must be considered
      when interpreting the outcomes.

PMID- 21852034
TI  - TLR4 signal transduction pathways neutralize the effect of Fas signals on
      glioblastoma cell proliferation and migration.
AB  - The Fas pathway is described as an activator of the glioblastoma proliferation by
      increasing the pathogenicity of this tumour. The lipopolysaccharide (LPS) pathway
      depending on Toll-like receptor 4 (TLR4) could limit the glioblastoma spreading.
      Here, Fas and TLR4 pathways were activated in glioblastoma cell lines by an
      agonist antibody and/or LPS treatment. Activation of the Fas pathway or of the
      TLR4 pathway induced cell proliferation. However, simultaneous treatment with
      agonist antibody and LPS decreased proliferation. This anti-proliferative effect
      was caspase dependent, and a decreased cell migration and matrix
      metalloproteinase (MMP)-9 expression were also observed. Both TLR4 and MMP-9 were
      highly expressed in human glioblastoma tissues. These data suggest that TLR4
      signal transduction pathways neutralize proliferation and migration induced by
      Fas pathway activation in glioblastoma cell lines.

PMID- 21852035
TI  - Combined treatment with exogenous estradiol and progesterone increases the
      incidence of breast cancer in TA2 mice without ovaries.
AB  - TA2 mice have a high incidence of spontaneous breast cancer without chemical
      stimulus. There are two proposed explanations for this phenomenon: one is
      gravidity and the frequency of pregnancies, and the other is related to the
      presence of the mouse mammary tumor virus (MMTV). MMTV is hormonally regulated
      and indirectly promotes tumor formation by leading to the activation of Wnt
      oncogenes through insertional mutagenesis. In order to clarify the relationship
      between estrogen, progesterone, MMTV, Wnt oncogenes and breast cancer, ovaries
      from virgin female TA2 mice were removed and the mice were treated with exogenous
      estradiol and progesterone in different patterns. This study found that the
      combination of exogenous estradiol and progesterone induced breast cancer
      formation in TA2 mice without ovaries. MMTV-LTR mRNA exhibited the highest
      expression in tumor tissue from the combination treatment group (CT). Mammary
      tissue from mice in the CT group had the highest Wnt1, Wnt5a, Wnt5b and Wnt10b
      mRNA expression levels. These results indicate that estradiol and progesterone
      act in a synergistic manner to upregulate MMTV, which subsequently induces breast
      cancer in TA2 mice. Various members of the Wnt gene family may play specific
      roles in different stages of carcinogenesis in TA2 mice.

PMID- 21852036
TI  - Volatile organics off-gassed among tobacco-exposed clothing fabrics.
AB  - This work evaluates the characteristics of short-term release of volatile and
      semi-volatile organic chemicals from clothing fabrics that are exposed to
      environmental tobacco smoke (ETS). Various fabrics were concurrently exposed to
      ETS in a controlled facility, and the chemicals off-gassed were sampled using
      solid phase micro-extraction coupled with GC/MS analysis. Toluene-reference
      concentration (TRC) was calculated for nine selected chemicals and compared. The
      number of chemicals identified from ETS-exposed fabrics ranged from 13 (polyester
      and acetate) to 32 (linen). All fabrics off-gassed formaldehyde, tetradecanoic
      acid and n-hexadecanoic acid, while seven out of eight fabrics emitted furfural,
      benzonitrile, naphthalene and decanal. Natural fibers of plant origin (cotton and
      linen) off-gassed higher concentrations (TRC>100 MUg/l) of chemicals that have
      low molecular weight (~100 or less) than did natural fibers of animal origin
      (wool and silk) and synthetic fibers. Conversely, wool and silk off-gassed more
      chemicals that are of high molecular weight (>200), such as TDA (TRC>100 MUg/l)
      and n-HDA (TRC>500 MUg/l), than did other fabrics. Fabric structure (for a
      particular material) significantly affects chemical off-gassing. Cotton typically
      used for polo shirt (knitted) off-gassed significantly (p<0.05) higher TRC for
      chemicals with molecular weight of ~100 (such as furfural) than did other cottons
      of woven style. The dyeing of fabric (white vs. black) had a limited effect on
      emission, while increasing contact time with ETS increased the intensity of
      chemical emissions. The mean TRC for cotton exposed for 12 min was nearly doubled
      than those exposed for 8min, but no difference existed for polyester.

PMID- 21852037
TI  - Spatial distribution of Trichinella britovi, T. spiralis and T. pseudospiralis of
      domestic pigs and wild boars (Sus scrofa) in Hungary.
AB  - Trichinellosis is a foodborne disease caused by the consumption of raw meat and
      raw meat-derived products from swine, horse and some game animals infected with
      nematode worms of the genus Trichinella. Between June 2006 and February 2011, 16
      million domestic pigs and 0.22 million wild boars (Sus scrofa) were tested for
      Trichinella sp. in Hungary. Trichinella infection was not found in any pigs
      slaughtered for public consumption. Nevertheless, Trichinella spiralis was
      detected in four backyard pigs when trace back was done following a family
      outbreak. Trichinella infection was demonstrated in 17 wild boars (0.0077%).
      Larvae from wild boars were identified as Trichinella britovi (64.7%), T.
      spiralis (29.4%) and Trichinella pseudospiralis (5.9%). Although the prevalence
      of Trichinella sp. infection in wild boars and domestic pigs is very low, the
      spatial analysis reveals that the level of risk differs by region in Hungary.
      Most of the T. britovi infected wild boars (63.6%) were shot in the north-eastern
      mountain area of Hungary; whereas domestic pigs and wild boars infected with T.
      spiralis were detected only in the southern counties bordering Croatia and
      Romania. In the north-western and central counties, the prevalence of Trichinella
      infection seems to be negligible.

PMID- 21852038
TI  - Eimeria species in dairy goats in Brazil.
AB  - The focus of this work is to determine the distribution and identify species of
      Eimeria parasites of dairy goats in the livestock of the National Goat and Sheep
      Research Center in Sobral, State of Ceara, Northeast Brazil. Results showed the
      presence of multiple species in 196 of 215 analyzed samples (91.2%). Fifty five
      out of these were from kids (28%) and 141 from adult goats (72%). Eight different
      Eimeria species were identified and their prevalence in the herd was: Eimeria
      alijevi Musaev, 1970 (26.7%), E. arloingi (Marotel, 1905) Martin, 1909 (20.6%),
      E. hirci Chevalier, 1966 (18%), E. ninakohlyakimovae Yakimoff & Rastegaieff, 1930
      (16.2%), E. jolchijevi Musaev, 1970 (8.7%), E. christenseni Levine, Ivens &
      Fritz, 1962 (6%), E. caprovina Lima, 1980 (2.8%) and E. caprina Lima, 1979 (1%).
      Moreover, E. ninakohlyakimovae showed higher prevalence in kids (97%), followed
      by E. arloingi and E. alijevi (88%). On the other hand, E. alijevi (77%) was more
      common in adult goats followed by E. hirci (74%) and E. ninakohlyakimovae (70%).
      The species E. caprina had low frequency in both kids (27%) and adult goats
      (13%). Data indicated that infection was relatively common among kids and adult
      goats. The implementation of a routine diagnostic strategy can be useful in
      maintaining Eimeria populations under monitoring and will enable the
      determination of its potential impact on dairy goat herds in Northeast Brazil.

PMID- 21852039
TI  - Widespread exposure to Sarcoptes scabiei in wild European rabbits (Oryctolagus
      cuniculus) in Spain.
AB  - Sarcoptic mange was recently described in the wild European rabbit (Oryctolagus
      cuniculus) in north-eastern Mediterranean Spain, the first such infection
      reported in this species anywhere in the world. This finding has created concern
      in conservationists and game managers given that an outbreak of mange after a
      translocation would have catastrophic consequences for naive rabbit populations
      in other parts of Spain. A retrospective serosurvey using an 'in house' ELISA
      test based on the use of a recombinant antigen aimed at determining the rates of
      contact with Sarcoptes scabiei was carried out on sera from 966 rabbits collected
      between 1993 and 2010 in Spain. Antibodies were found in 13% of wild rabbits in
      60% of the 53 areas surveyed, as well as in 16 of the 17 Spanish provinces and
      islands studied. Seropositive rabbits were found amongst the oldest samples
      analyzed and in all studied years. Antibodies were also detected in 36% of
      rabbits from the protected island of Dragonera, where rabbits have probably not
      been released since the 1970s. On Mallorca, where 89 rabbits were inspected for
      both lesions and antibodies, the prevalence of lesions (5.6%) was much lower than
      the seroprevalence (22.5%), indicating that rabbits often survive infection or
      that ELISA detects infected rabbits before they develop visible lesions.
      Seroprevalence was higher in areas with medium levels of rabbit abundance, no
      restocking and high rainfall. The results show that mange is widespread in
      rabbits and that the mite is not a recent introduction. Thus, sarcoptic mange
      could be considered as an enzootic disease in the wild rabbit and so prophylactic
      measures implemented during rabbit translocations are to be encouraged to avoid
      local outbreaks in naive populations.

PMID- 21852040
TI  - Vector-borne parasitic zoonoses: emerging scenarios and new perspectives.
AB  - Changing climate is not the only driver for alterations in the dynamic
      interaction between arthropod vectors of zoonotic parasites and their hosts,
      including humans. A suite of other factors ranging from urbanization and
      deforestation to changing demographics in both developing and developed
      countries, the impact of the recent economic crisis, increased global movement of
      people and animals and follow-on effects of major catastrophes. This article
      reviews the most important vector-borne parasites of zoonotic concern that are
      changing/expanding their distribution patterns in both endemic and/or previously
      non-endemic areas. We include the discussion of the changing aspects of malaria,
      leishmaniasis, babesiosis, Chagas disease as well as of some spirurid and
      filarioid nematodes.

PMID- 21852041
TI  - Intramuscular inoculation of cattle with Sarcocystis antigen results in focal
      eosinophilic myositis.
AB  - Bovine eosinophilic myositis (BEM) is a subclinical myopathy characterized by
      multifocal white to grey-green discolorations in skeletal muscles, heart, tongue
      and oesophagus. These lesions are found at slaughter or during meat cutting and
      result in considerable economic losses. The etiology and pathogenesis are
      unclear, although it has been suggested, that Sarcocystis species are involved.
      To elucidate their role, two calves were repeatedly injected intramuscularly with
      adjuvanted Sarcocystis antigen. The morphological changes at the injection sites
      in these calves were histologically and immunohistochemically compared to
      spontaneous lesions from 44 BEM condemned carcasses sampled in slaughterhouses.
      Experimental intramuscular injection of Sarcocystis antigen resulted in lesions
      at the injection sites that were similar to the lesions of natural cases of BEM.
      They were characterized by massive infiltration of eosinophilic granulocytes,
      reactive macrophages (MAC387(+) cells), T-cells (CD3(+)) and B-cells (CD20(+)).
      Both in the experimental and in the natural cases, COX-2 expression was present
      in endothelial cells adjacent to lesional areas. MHC class II(+) staining was
      found amongst others in muscle cells surrounding the lesion. These results show
      that Sarcocystis antigens can induce an inflammatory response in bovine muscle
      having the characteristics of natural BEM.

PMID- 21852042
TI  - Phylogenetic analysis of Sarcocystis nesbitti (Coccidia: Sarcocystidae) suggests
      a snake as its probable definitive host.
AB  - Sarcocystis nesbitti was first described by Mandour in 1969 from rhesus monkey
      muscle. Its definitive host remains unknown. 18S rRNA gene of S. nesbitti was
      amplified, sequenced, and subjected to phylogenetic analysis. Among those
      congeners available for comparison, it shares closest affinity with those species
      of Sarcocystis which use snakes as definitive hosts. We therefore hypothesize
      that a snake may serve as the definitive host for S. nesbitti.

PMID- 21852044
TI  - A clinical evaluation of Biobrane((r)) and Suprathel((r)) in acute burns and
      reconstructive surgery.
AB  - BACKGROUND: In the treatment of superficial partial-thickness burns, various skin
      substitutes and temporary dressings offer potential advantages over traditional
      treatments. Nonetheless, the search for an ideal temporary skin substitute or
      biosynthetic wound dressing is still a continuous quest. This research aimed to
      provide objective data on the long-term outcome of Biobrane((r)) and
      Suprathel((r)). METHODS: Eight months after the initial burn treatment of
      Biobrane((r)) and Suprathel((r)), skin elasticity was measured objectively using
      a Cutometer((r)) and the scarring process was quantified using the Vancouver Scar
      Scale (VSS). RESULTS: The median healing time for patients treated with
      Biobrane((r)) was up to 1.8 days shorter then the Suprathel((r)) group. Regarding
      the Vancouver Scar Scale (VSS), neither the single parameter, nor the total score
      were significantly different in both groups. In comparison, the Biobrane((r))
      group demonstrated superior Cutometer((r)) parameters in regards to maximal
      extension, elasticity, retraction and pliability. Despite higher levels of
      Biobrane((r)) group, the differences in the viscoelastic analysis of both
      substitutes did not vary significantly. CONCLUSION: Using both substitutes, we
      observed satisfying results in superficial partial-thickness burn treatment,
      without any significant differences. Since the treatment of burned patients is
      associated with high socioeconomic load, the cost factor should be one of the
      most important criteria in dermal substitute selection.

PMID- 21852045
TI  - Comparison of Suprathel(r) and allograft skin in the treatment of a severe case
      of toxic epidermal necrolysis.

PMID- 21852046
TI  - Comments on "Analysis of factors influencing limb amputation in high-voltage
      electrically injured patients".

PMID- 21852047
TI  - Train surfing and other high voltage trauma: differences in injury-related
      mechanisms and operative outcomes after fasciotomy, amputation and soft-tissue
      coverage.
AB  - BACKGROUND: In the context of scarce reports on train surfers among high voltage
      electric injuries, we conducted a retrospective review between January 1994 and
      December 2008. METHODS: After matching for inclusion criteria we reviewed patient
      records of 37 true high voltage injuries (12 train surfers [TS] and 25 other high
      voltage injuries [HV]). RESULTS: TS were significantly younger (TS 15.8 years vs.
      HV 33.3 years, p<0.0001), and had a greater %TBSA (TS 49.7%TBSA vs. HV 21.5%TBSA,
      p=0.0003) without affecting the median length-of-stay (TS 52 days vs. HV 49 days)
      or number of operations (TS 4 vs. HV 3). TS had different injury patterns, with a
      higher percentage of affected extremities (TS 72.9% vs. HV 52.0%, p=0.0468) and
      associated injuries (TS 58% vs. HV 20%, n.s.) than HV. Both groups demonstrated
      comparable fasciotomy (TS 71.4% vs. HV 55.8%) and amputation rates (TS 17.1% vs.
      HV 15.4%). While TS required less flaps (TS 3/12 vs. HV 18/25; p=0.0153), soft
      tissue reconstruction revealed an overall low incidence of complication rates
      (one partial pedicled flap loss and two total free flap losses). CONCLUSIONS:
      Train surfers have proven to be a distinct group of patients among high-voltage
      injuries notably as a result of a younger age, a shorter electric contact
      duration and higher velocity-induced trauma. With a possibly declining trend of
      train surfing-related accidents in an aging society, it will be interesting to
      see if emerging economies will face comparable phenomena, for which prevention
      strategies remain key.

PMID- 21852049
TI  - A case report of clinically significant coagulopathy associated with aerosolized
      heparin and acetylcysteine therapy for inhalation injury.

PMID- 21852050
TI  - Low CSF oxytocin reflects high intent in suicide attempters.
AB  - Data from animal studies suggest that oxytocin is an important modulating
      neuropeptide in regulation of social interaction. One human study has reported a
      negative correlation between CSF oxytocin levels, life history of aggression and
      suicidal behaviour. We hypothesized that CSF oxytocin levels would be related to
      suicidal behaviour, suicide intent, lifetime interpersonal violence and suicide
      risk. 28 medication free suicide attempters and 19 healthy volunteers
      participated in this cross sectional and longitudinal study. CSF and plasma
      morning basal levels of oxytocin were assessed with specific radio-immunoassays.
      The Beck Suicide Intent Scale (SIS), the Freeman scale and the Karolinska
      Interpersonal Violence Scale (KIVS) were used to assess suicide intent and
      lifetime violent behaviour. All patients were followed up for cause of death. The
      mean follow-up was 21 years. Suicide attempters had lower CSF oxytocin levels
      compared to healthy volunteers p=0.077. In suicide attempters CSF oxytocin showed
      a significant negative correlation with the planning subscale of SIS. CSF
      oxytocin showed a significant negative correlation with suicide intent, the
      planning subscale of SIS and Freeman interruption probability in male suicide
      attempters. Correlations between plasma oxytocin levels and the planning subscale
      of SIS and Freeman interruption probability were significant in male suicide
      attempters. Lifetime violent behaviour showed a trend to negative correlation
      with CSF oxytocin. In the regression analysis suicide intent remained a
      significant predictor of CSF oxytocin corrected for age and gender whereas
      lifetime violent behaviour showed a trend to be a predictor of CSF oxytocin.
      Oxytocin levels did not differ significantly in suicide victims compared to
      survivors. CSF oxytocin may be an important modulator of suicide intent and
      interpersonal violence in suicide attempters.

PMID- 21852051
TI  - Cortisol levels in response to starting school in children at increased risk for
      social phobia.
AB  - BACKGROUND: Research on depression has identified hyperactivity of the HPA axis
      as a potential contributory factor to the intergenerational transmission of
      affective symptoms. This has not yet been examined in the context of social
      phobia. The current study compared HPA axis activity in response to a universal
      social stressor (starting school) in children of 2 groups of women: one with
      social phobia and one with no history of anxiety (comparison group). To determine
      specificity of effects of maternal social phobia, a third group of children were
      also examined whose mothers had generalised anxiety disorder (GAD). METHOD:
      Children provided salivary cortisol samples in the morning, afternoon and at
      bedtime across 3 time-blocks surrounding the school start: a month before
      starting school (baseline), the first week at school (stress response), and the
      end of the first school term (stress recovery). Child behavioural inhibition at
      14 months was assessed to explore the influence of early temperament on later
      stress responses. RESULTS: All children displayed an elevation in morning and
      afternoon cortisol from baseline during the first week at school, which remained
      elevated until the end of the first term. Children in the social phobia group,
      however, also displayed an equivalent elevation in bedtime cortisol, which was
      not observed for comparison children or for children of mothers with GAD.
      Children in the social phobia group who were classified as 'inhibited' at 14
      months displayed significantly higher afternoon cortisol levels overall. SUMMARY:
      A persistent stress response to school in the morning and afternoon is typical
      for all children, but children of mothers with social phobia also display
      atypical elevations in evening cortisol levels when at school--signalling longer
      term disruption of the circadian rhythm in HPA axis activity. This is the first
      study to report HPA axis disruption in children at increased risk of developing
      social phobia. Future research should determine whether this represents a pathway
      for symptom development, taking early temperament into account.

PMID- 21852052
TI  - The in vivo functions of a histidine-rich protein Hpn in Helicobacter pylori:
      linking gastric and Alzheimer's diseases together?
AB  - Helicobacter pylori causes such gastric diseases as gastritis, peptic
      ulcerations, gastric cancer and MALT lymphoma. Hpn is a histidine-rich protein
      abundant in this bacterium and forms amyloid-like oligomers in physiologically
      relevant conditions. Here we proposed the in vivo functions of this protein with
      relevance to its physical locations. The collective evidence presented here shed
      some light on the pathologic mechanisms of H. pylori infections, with emphasis on
      the bacterial colonization in the gastric environment, pathological effects to
      the gastric epithelial cells and the possible link to Alzheimer's disease.

PMID- 21852053
TI  - An overlooked aspect of the human breast: areolar glands in relation with
      breastfeeding pattern, neonatal weight gain, and the dynamics of lactation.
AB  - The early nursing-sucking relationship is not to be taken for granted in humans.
      A number of factors can either facilitate or mitigate its optimal establishment
      on the mother's or newborn's sides. Among these factors, a morphological feature
      of human mothers' breasts--the areolar glands (AG)--has been identified as
      potentially important. Three day-old infants display attraction during the
      presentation of the native secretions of the AG, suggesting that they could
      influence the newborn's behaviour during breastfeeding. The present study
      assessed this topic in a sample of 121 Caucasian mother-infant dyads. The areolae
      of these women were screened during the first 3 postnatal days in parallel with
      the infant's sucking performance, body weight fluctuations and time to lactation
      onset. On average, 97% of the women bore AG, 80.2% having 1-20 units per areola
      and 33% showing AG excreting a visible fluid. The endowment in AG appeared
      positively linked with neonatal growth after birth and with the speed of
      lactation onset: infants of primiparous women with lower AG numbers had a lower
      weight gain than those of mothers with higher AG numbers. Further, it took longer
      to primiparae with lower AG counts to set on lactation. This study confirms and
      extends the fact that AG, in interaction with maternal experience, might
      influence the initiation of the breastfeeding relationship.

PMID- 21852054
TI  - Methods used in cross-cultural comparisons of somatic symptoms and their
      determinants.
AB  - This paper is the third in a series of reviews of cross-cultural studies of
      symptoms at midlife. The goal of this review is to examine methods used
      previously in cross-cultural studies of menopause and women's health at midlife
      to (1) identify challenges in the measurement of somatic symptoms across cultures
      and (2) recommend questions and tools that can be used in future research. This
      review also aims to examine the determinants of somatic symptoms. The review
      concludes that methods used for assessing somatic symptoms differ across studies.
      Somatic symptoms, particularly, aches, pain, and fatigue have a high prevalence.
      Statistically significant differences were seen in the prevalence of somatic
      symptoms across cultures. Based on the number of studies that demonstrated cross
      cultural differences in symptom prevalence, we recommend that the following
      symptoms be included in future studies of symptoms at midlife: headaches,
      aches/pain, palpitations, dizziness, fatigue, breathing difficulties, numbness or
      tingling, and gastrointestinal difficulties. We also recommend that objective
      measures of physical function be administered when possible to supplement
      subjective self-evaluation.

PMID- 21852055
TI  - USGS42 and USGS43: human-hair stable hydrogen and oxygen isotopic reference
      materials and analytical methods for forensic science and implications for
      published measurement results.
AB  - Because there are no internationally distributed stable hydrogen and oxygen
      isotopic reference materials of human hair, the U.S. Geological Survey (USGS) has
      prepared two such materials, USGS42 and USGS43. These reference materials span
      values commonly encountered in human hair stable isotope analysis and are
      isotopically homogeneous at sample sizes larger than 0.2 mg. USGS42 and USGS43
      human-hair isotopic reference materials are intended for calibration of delta(2)H
      and delta(18)O measurements of unknown human hair by quantifying (1) drift with
      time, (2) mass-dependent isotopic fractionation, and (3) isotope-ratio-scale
      contraction. While they are intended for measurements of the stable isotopes of
      hydrogen and oxygen, they also are suitable for measurements of the stable
      isotopes of carbon, nitrogen, and sulfur in human and mammalian hair. Preliminary
      isotopic compositions of the non-exchangeable fractions of these materials are
      USGS42(Tibetan hair)delta(2)H(VSMOW-SLAP) = -78.5 +/- 2.30/00 (n = 62) and
      delta(18)O(VSMOW-SLAP) = +8.56 +/- 0.100/00 (n = 18) USGS42(Indian
      hair)delta(2)H(VSMOW-SLAP) = -50.3 +/- 2.80/00 (n = 64) and delta(18)O(VSMOW
      SLAP) = +14.11 +/- 0.100/00 (n = 18). Using recommended analytical protocols
      presented herein for delta(2)H(VSMOW-SLAP) and delta(18)O(VSMOW-SLAP)
      measurements, the least squares fit regression of 11 human hair reference
      materials is delta(2)H(VSMOW-SLAP) = 6.085delta(2)O(VSMOW-SLAP) - 136.00/00 with
      an R-square value of 0.95. The delta(2)H difference between the calibrated
      results of human hair in this investigation and a commonly accepted human-hair
      relationship is a remarkable 340/00. It is critical that readers pay attention to
      the delta(2)H(VSMOW-SLAP) and delta(18)O(VSMOW-SLAP) of isotopic reference
      materials in publications, and they need to adjust the delta(2)H(VSMOW-SLAP) and
      delta(18)O(VSMOW-SLAP) measurement results of human hair in previous
      publications, as needed, to ensure all results on are on the same scales.

PMID- 21852056
TI  - Quantification of unfractionated heparin in human plasma and whole blood by means
      of novel fluorogenic anti-FXa assays.
AB  - Novel and sensitive plate-based fluorogenic anti-factor Xa (FXa) assays were
      investigated to quantify unfractionated heparin (UFH) in human plasma and whole
      blood within the therapeutic ranges of 0-1.6 U/mL and 0-0.8 U/mL, respectively.
      Two fluorogenic anti-FXa assay methods were defined for low (0-0.6 U/mL) and high
      (0.6-1.2 U/mL) pharmacologically relevant UFH concentration ranges in pooled
      human plasma. In both cases significant differences were observed at intervals of
      0.2 U/mL (P<0.05). The semi-logarithmic plots of the calibration curves in the
      low and high UFH range were both fitted to linear regressions with correlation
      coefficients of 0.96 and >0.99, respectively. The assay was also optimized for
      whole blood which was capable of differentiating UFH concentrations at intervals
      of 0.2 U/mL (P<0.05) in the range of 0-0.4 U/mL. The statistically different
      results were fitted to a linear regression with a correlation coefficient of
      >0.99. The results obtained in this study could assist diagnostic laboratories
      towards improved monitoring of UFH therapy.

PMID- 21852058
TI  - Direct trapping and analysis of hemoglobin in flowing fluid using membrane
      immobilized anti-haptoglobin antibody.
AB  - Haptoglobin is known to bind to hemoglobin during intravascular hemolysis.
      Membrane-immobilized anti-haptoglobin antibody, which was produced after antibody
      was isolated by non-denaturing two-dimensional electrophoresis, was transferred
      to a polyvinylidene difluoride membrane and was stained using Ponceau S. The
      proteins bound to the membrane-immobilized anti-haptoglobin antibody were
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix
      assisted laser desorption ionization/time-of-flight mass spectrometry. Hemoglobin
      was specifically obtained when the membrane-immobilized anti-haptoglobin antibody
      was incubated with human serum obtained from hemolysis blood. Furthermore,
      hemoglobin in the flowing fluid was captured by the membrane-immobilized anti
      haptoglobin antibody and analyzed directly. The results indicate that hemolysis
      can be examined by direct trapping and analysis of hemoglobin under physiological
      conditions.

PMID- 21852057
TI  - Molecular and protein characterization of two species of the latrunculin
      producing sponge Negombata from the Red Sea.
AB  - Red Sea sponges offer a potential for production of novel drugs and prototypes.
      The genus Negombata is a type of sponges abundant in the Red Sea. This sponge
      produces latrunculins that have well documented antitumor activity in addition to
      antimicrobial and antiviral effects. The identification of Negombata species is
      based on morphology and microscopical examination of megascleres of spicules.
      However, these criteria have proven to be unreliable for identification.
      Therefore, this study was established to test the accuracy of the spicules based
      taxonomy against molecular and protein profiles for the two species of Negombata:
      N. magnifica and N. corticata. About 700 bp of cytochrome c oxidase I gene was
      sequenced from the tissues of the two Negombata species. Additionally total
      proteins were extracted from Negombata samples collected from different locations
      during different seasons and separated by denaturing polyacrylamide gel
      electrophoresis. Characteristic different protein profiles were obtained for both
      species. The data obtained from cytochrome c oxidase I gene sequencing and
      protein profiles can reliably differentiate between different species of
      Negombata in the Red Sea.

PMID- 21852059
TI  - Simultaneous determination of Maillard reaction impurities in memantine tablets
      using HPLC with charged aerosol detector.
AB  - A gradient high performance liquid chromatographic (HPLC) method using charged
      aerosol detection (CAD) was developed for the simultaneous determination of
      impurities formed by the Maillard reaction in memantine tablets. These impurities
      were a memantine-lactose adduct (ML), a memantine-dimethylamino glycine adduct
      (DMAG), a memantine-galactose adduct (MGAL), and a memantine-glucose adduct
      (MGLU). The chromatographic separation was performed on a Synergy Hydro RP column
      (100 mm*3 mm, 2.5 MUm particles) from Phenomenex with gradient elution using
      mobile phases consisting of 0.6% (v/v) of heptafluorobuturic acid (HFBA) in two
      acetonitrile-isopropyl alcohol-water mixtures. The method validation for the
      impurities included linearity, accuracy by spike recovery, precision, limits of
      detection and quantitation, and robustness. The method was sensitive for these
      non-chromophoric impurities down to 0.4-0.6 MUg/mL (0.02-0.03% of the memantine
      drug substance). The effect of mobile phase HFBA concentration on chromatographic
      resolution and peak shape was investigated, and the effect of sample diluent
      acidification on method accuracy via spike recovery was studied. The operational
      simplicity of the CAD detector for routine quality control has been demonstrated.

PMID- 21852060
TI  - Identification of photodegradation product of amisulpride by ultra-high-pressure
      liquid chromatography-DAD/ESI-quadrupole time-of-flight-mass spectrometry.
AB  - Photostability of amisulpride under UVA irradiation in methanol solution was
      investigated and structural elucidation of its photodegradation products was
      performed. For the purpose of the quantitative and qualitative analysis of
      amisulpride and the stress degradation products elucidation, the reversed phase
      UHPLC-DAD system coupled with accurate mass hybrid ESI-Q-TOF mass spectrometer
      was used. During one run (10 min) with the use of auto MS/MS mode all essential
      data for the determination of photodegradation kinetics and for the structural
      formulas elucidation of the products was collected. Four degradation products
      were found and their masses with high accuracy (0.53-3.05 ppm) and formulas were
      obtained--258.0666 (C(10)H(14)N(2)O(4)S), 367.1564 (C(17)H(25)N(3)O(4)S),
      341.1412 (C(15)H(23)N(3)O(4)S) and 385.1665 (C(17)H(27)N(3)O(5)S). For all the
      analyzed compounds MS/MS fragmentation spectra were obtained (collision energy
      19.8-26.1 V) allowing structural elucidation of unknown degradation products and
      indicating photodegradation pathways of amisulpride. UHPLC-DAD/ESI-Q-TOF system
      was found to be a powerful analytical tool for the fast and accurate stability
      analysis of pharmaceutical substances.

PMID- 21852061
TI  - Phenytoin-induced drug reaction with eosinophilia and systemic symptoms (DRESS)
      syndrome: a case report from the emergency department.
AB  - BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is
      an uncommon but serious hypersensitivity drug reaction most frequently associated
      with antiepileptics. Clinical manifestations include rash, fever, and visceral
      organ involvement, most commonly hepatitis. The mortality rate associated with
      DRESS syndrome is approximately 10%, the majority due to fulminant liver failure.
      OBJECTIVES: We report one case of phenytoin-induced DRESS syndrome in a patient
      who presented to the Emergency Department (ED). Our objectives for this case
      report include: 1) to learn the importance of DRESS syndrome; 2) to recognize the
      signs and symptoms of DRESS syndrome; 3) to know what diagnostic studies are
      indicated; and 4) to learn the appropriate treatment. CASE REPORT: We report one
      case of phenytoin-induced DRESS syndrome in a 34-year-old man, previously on
      phenytoin for seizure prophylaxis, who presented to the ED with 5 days of
      worsening symptoms including generalized rash, fever, tongue swelling, and
      dysphagia. Laboratory results revealed an eosinophilia and elevated liver
      enzymes. With initiation of steroids, the transaminitis improved despite
      increasing eosinophilia and development of an atypical lymphocytosis. Fever and
      angioedema resolved with improvement of the rash, and the patient was discharged
      on hospital day 3. CONCLUSION: Given the significant mortality related to DRESS
      syndrome, ED staff should have a low threshold for suspecting the condition in
      patients who present with unusual complaints and skin findings after starting any
      antiepileptic drug. Early diagnosis and prompt treatment with corticosteroids is
      imperative.

PMID- 21852062
TI  - Eczema herpeticum.

PMID- 21852063
TI  - Goal setting as a health behavior change strategy in overweight and obese adults:
      a systematic literature review examining intervention components.
AB  - OBJECTIVE: This paper describes goal setting components used for behavior change
      specific to diet and physical activity in community-based interventions targeting
      overweight and obese adults. METHODS: A systematic literature review was
      conducted. Studies were evaluated using the S.T.A.R.T. (Specificity, Timing,
      Acquisition, Rewards and feedback, and Tools) criteria which were developed for
      the purposes of this paper in order to elucidate which intervention features
      elicit optimal health behavior outcomes. RESULTS: Eighteen studies were included.
      Based on the S.T.A.R.T. criteria, it was determined that developing specific
      goals that are in close proximity, involve the participant in acquisition, and
      incorporate regular feedback, are common features in this context. CONCLUSION:
      Goal setting can be useful for effecting health behavior changes in this
      population. However, as different intervention components were often implemented
      concurrently (e.g., education sessions, self-monitoring records), it was not
      possible to ascertain which were responsible for positive changes independently.
      PRACTICE IMPLICATIONS: Goal setting shows promise as a tool that can be
      incorporated into weight reduction programs by health care professionals and
      researchers. Studies are warranted to identify the specific mechanisms through
      which individuals with overweight or obesity can apply the S.T.A.R.T. criteria
      with respect to goal setting for the purposes of weight loss.

PMID- 21852064
TI  - An examination of the validity of EPSCALE using factor analysis.
AB  - OBJECTIVE: To examine the validity and utility of the Explanation and Planning
      Scale (EPSCALE) instrument, a widely used scale for teaching and assessment of
      explanation and planning skills used by clinicians during the medical interview.
      METHODS: Data obtained across 4 OSCE stations during medical student final MB
      examinations. Exploratory factor analysis, using a single factor and two factor
      models (based on prior theory) and a six factor empirical model, suggested by
      parallel analysis. PARTICIPANTS: 124 medical students sitting final MB
      examinations at the University of Cambridge. RESULTS: A single factor model
      represented a very poor fit. A two factor model with factors labelled
      'Explanation' and 'Planning' produced an improved fit, but the best was seen with
      a six factor model, with factors which broadly corresponded to the domains of the
      Calgary-Cambridge guide. CONCLUSIONS: These factor models provide supportive
      evidence for the construct validity of EPSCALE. PRACTICE IMPLICATIONS: EPSCALE
      can justifiably be used in the assessment of shared-decision making skills.

PMID- 21852065
TI  - [Locoregional anaesthesia and echography].

PMID- 21852066
TI  - Osteoporosis Canada 2010 guidelines for the assessment of fracture risk.
AB  - Osteoporosis Canada's 2010 Clinical Practice Guidelines for the Diagnosis and
      Management of Osteoporosis in Canada focus on the clinical impact of fragility
      fractures, and on the assessment and management of women and men at high risk for
      fragility fracture. These guidelines now integrate a 10-year absolute fracture
      risk prediction into an overall management approach by using validated risk
      assessment tools. There currently is a large gap between optimal practices and
      those that are now being provided to Canadians with osteoporosis. These
      guidelines are part of a concerted effort to close this gap. Key changes from the
      2002 guidelines of interest and relevance to radiologists are highlighted in this
      report.

PMID- 21852067
TI  - Visual outcome and contrast sensitivity after photorefractive keratectomy in low
      to moderate myopia: wavefront-optimized versus conventional methods.
AB  - PURPOSE: To compare visual outcomes and contrast sensitivity after wavefront
      optimized or conventional photorefractive keratectomy (PRK) in myopic patients
      with or without astigmatism. SETTING: Vanak Eye Surgery Center, Tehran, Iran.
      DESIGN: Comparative case series. METHODS: Patients with low to moderate myopia
      with or without astigmatism were allocated into 2 groups. The study group was
      treated with wavefront-optimized PRK (Allegretto Wave Eye-Q software version
      2.020 default treatment) and the control group, with conventional PRK (Technolas
      217z). In all cases, treatments were bilateral and performed with the same
      device. Baseline and 3-month postoperative measures were uncorrected and
      corrected distance visual acuities, manifest refraction, and contrast
      sensitivity. RESULTS: Each group comprised 66 eyes. The mean preoperative
      spherical equivalent refraction improved from -2.99 diopters (D) +/- 1.02 (SD)
      preoperatively to -0.08 +/- 0.26 D 3 months postoperatively in the study group
      and from -2.66 +/- 0.95 D to 0.01 +/- 0.30 D, respectively, in the control group.
      In both groups, the postoperative mesopic and photopic contrast sensitivity
      decreased significantly at most spatial frequencies. The postoperative decrease
      in contrast sensitivity in both groups was comparable except at spatial
      frequencies of 3 cycles per degree (cpd) under mesopic conditions and 12 cpd
      under photopic conditions, frequencies at which the control group had a greater
      reduction. CONCLUSIONS: Visual acuity and refractive error outcomes were similar
      in both treatment groups. After 3 months, mesopic and photopic contrast
      sensitivity were significantly decreased in both groups; the reduction in the 2
      groups was almost comparable. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 21852068
TI  - Repeatability of automatic measurements by a new Scheimpflug camera combined with
      Placido topography.
AB  - PURPOSE: To assess the repeatability of anterior segment measurements performed
      by a Scheimpflug camera combined with Placido corneal topography (Sirius) in
      unoperated, post-refractive surgery, and keratoconus eyes. SETTING: Private
      clinical ophthalmology practice. DESIGN: Evaluation of diagnostic test or
      technology. METHODS: Three consecutive scans were acquired for each eye. The
      following parameters were evaluated: simulated keratometry, posterior corneal
      power, mean pupil power (ie, corneal power assessed by ray tracing through the
      anterior and posterior corneal surfaces), corneal asphericity, thinnest and apex
      corneal thickness, aqueous depth, anterior chamber volume, and corneal spherical
      aberration. Repeatability was assessed using test-retest variability, the
      coefficient of variation, and the intraclass correlation coefficient (ICC).
      RESULTS: Sixty-four unoperated eyes, 17 eyes that had myopic excimer laser
      surgery, and 13 eyes with keratoconus were analyzed. High repeatability was
      achieved for most parameters in the 3 groups, with an ICC higher than 0.99 for
      all measurements except posterior corneal power and mean pupil power in
      keratoconus (ICC, 0.868 and 0.976, respectively), anterior and posterior
      asphericity in normal eyes (ICC, 0.904 and 0.977, respectively), and spherical
      aberration in normal eyes (ICC, 0.806), post-refractive surgery eyes (ICC,
      0.980), and keratoconus eyes (ICC, 0.981). CONCLUSION: The anterior segment
      measurements provided by the new Scheimpflug camera-Placido corneal topography
      system were highly repeatable and can be relied on in clinical routine and for
      research purposes. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 21852069
TI  - Estimation of corneal power after myopic laser refractive surgery: comparison of
      methods against back-calculated corneal power.
AB  - PURPOSE: To compare methods of corneal power estimation after myopic laser
      refractive surgery with back-calculated corneal power (K). SETTING: Private
      practice, Edmonton, Alberta, Canada. DESIGN: Case series. METHODS: Patients with
      previous myopic laser surgery followed by cataract extraction were studied. Back
      calculated K obtained with the Holladay IOL Consultant was compared with that
      obtained by the clinical history method (CHM), the modified Maloney method, an
      adaptation of the Maloney method using individualized Orbscan IIz-derived
      posterior corneal power values, Orbscan IIz quantitative area topography, and the
      Gaussian optics formula. A mixed effects linear model was used for analysis.
      RESULTS: The mean spherical equivalent (SE) before laser treatment was -6.43
      diopters (D) +/- 3.52 (SD). The estimated means of all methods except those
      obtained with the CHM, modified Maloney method, 2.0 mm total axial map, 1.5 mm
      total mean map, and 1.5 mm total optical map were significantly different from
      the mean of the back-calculated K. Estimates from the 1.5 mm total mean map were
      generally 0.06 D higher. The 2.0 mm total axial map, modified Maloney method, 1.5
      mm total optical map, and CHM underestimated corneal power by 0.11 D, 0.13 D,
      0.22 D, and 0.26 D, respectively. Unit increases in optical zone and pre-laser
      myopic SE were associated with decreases in corneal power of 1.58 D (P = .047)
      and 0.55 D (P = .0001), respectively. CONCLUSION: The modified Maloney method,
      2.0 mm total axial map, 1.5 mm total mean map and 1.5 mm total optical map of the
      Orbscan IIz may provide estimates closer to the back-calculated K than the CHM.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 21852070
TI  - Vancomycin-resistant coagulase negative Staphylococcus endophthalmitis following
      cataract surgery.

PMID- 21852071
TI  - Psychometric properties and factor structure of the Behavior Problems Inventory
      (BPI-01) in a Swedish community population of adults with intellectual
      disability.
AB  - The aim of the present study was to evaluate the psychometric properties and
      factor structure of the Behavior Problems Inventory (BPI-01) in a community
      population. The Swedish version of the BPI-01 was administered by interviewing
      care staff of all adults (n = 915) with administratively defined intellectual
      disabilities (IDs) living in Orebro County, Sweden. Sixty-two percent of the
      participants had at least one behavior problem. Altogether, 30.9% showed self
      injurious behavior, 41.3% stereotyped behavior, and 34.8% aggressive/destructive
      behavior. All but the self-injurious behavior scale reached acceptable levels of
      internal consistency. Confirmatory factor analysis supported the
      unidimensionality of the subscales as well as the proposed three factor structure
      of the original BPI-01. The present study demonstrates that the three subscales
      are highly similar constructs across different language and cultural settings,
      and that the BPI-01 is applicable in research on populations with varying mental
      functioning, diagnoses, ages, and living arrangements.

PMID- 21852072
TI  - Poor agreement found between self-report and a public registry on duration of
      sickness absence.
AB  - OBJECTIVE: To investigate the agreement between self-report and a public registry
      regarding the occurrence and duration of sickness absence (SA) in patients with
      sciatica. STUDY DESIGN AND SETTING: Observational 2-year longitudinal study
      including 227 patients. Self-report SA data were obtained by postal
      questionnaires covering recall periods of 3, 6, and 12 months and compared with
      data from the Norwegian National Sickness Benefit Register. RESULTS: The percent
      agreement on the occurrence of SA between self-report and registry was above 85%
      for all three recall periods. The patients overestimated the duration of their SA
      by 2.4 (95% confidence interval, 1.1-3.7) weeks for the 3-month recall period.
      The 95% limits of agreement were generally wide, varying from -12.5 to 17.3 weeks
      for the 3-month recall period to -38.8 to 37.2 weeks for the 12-month period. For
      the 3-, 6-, and 12-month recall periods, 48.1%, 29.8%, and 27.3% of the patients
      reported an SA duration that differed by <=1 week from that recorded in the
      registry. CONCLUSION: Mainly because of low precision, the agreement on the
      duration of SA was poor for all three recall periods. The agreement between self
      report and registry regarding the occurrence of SA was good.

PMID- 21852073
TI  - The harvesting and insetting of a chimeric anterolateral thigh flap to
      reconstruct through and through cheek defects.
AB  - This technical note describes the harvesting and insetting of a chimeric
      anterolateral thigh (ALT) flap to reconstruct a through and through cheek defect.
      Two perforators originating from the lateral circumflex femoral system that
      joined to the same mother vascular source were identified. Two separate skin
      paddles based on the perforators were designed and appropriately inset to repair
      the mucosal lining and the cheek skin. Careful harvesting and insetting of the
      chimeric ALT flap ensures a good cosmetic and reconstructive effect in the
      reconstruction of the through and through cheek defect.

PMID- 21852074
TI  - Accuracy of self-reported medical problems in patients with alcohol dependence
      and co-occurring schizophrenia or schizoaffective disorder.
AB  - BACKGROUND: Schizophrenia and alcohol dependence (AD) are both major risk factors
      for a variety of medical problems, yet little is known about the medical status
      of patients in whom both conditions coexist. OBJECTIVE: The objectives of this
      study are to assess accuracy of self-reported medical problems and to compare the
      accuracy reports in patients with schizophrenia or schizoaffective disorder and
      co-occurring AD compared to patients with AD only and to controls. Our hypothesis
      was that medical problems are under-reported in patients with co-occurring
      disorders, possibly due to the combination of alcohol use and symptoms of
      schizophrenia. METHODS: Self-reported medical diagnoses were recorded and
      compared to medical records obtained from all area hospitals in 42 patients with
      schizophrenia and AD, 44 patients with schizoaffective disorder and AD, 41
      patients with AD only, and 15 control subjects. Patients underwent medical
      history, physical examination, and review of medical records. RESULTS: Patients
      with schizophrenia or schizoaffective disorder and co-occurring AD underreported
      their medical problems significantly more than patients with AD only and
      controls. Accuracy of self report was significantly lower in patients with
      schizophrenia-spectrum disorders plus co-occurring alcohol dependence than in AD
      alone or in controls. The most commonly underreported diagnoses included coronary
      artery disease, chronic renal failure, seizure disorder, hyperlipidemia, asthma
      and hypertension. DISCUSSION: In order to detect potentially unreported medical
      conditions in patients with co-occurring schizophrenia/schizoaffective disorder
      and alcohol dependence, the use of targeted screening questionnaires is
      recommended in addition to physical examination and thorough review of medical
      records.

PMID- 21852075
TI  - Clinical parameters of circadian rhythms in affective disorders.
AB  - Many affective disorders show episode cycling and the classic symptoms of these
      disorders show rhythmicity, such as diurnal variation in mood. There are several
      plausible stress-vulnerability models that suggest links between these observed
      phenomena and the circadian system. For example, an individual with increased
      sensitivity to social rhythm disruption may be more at risk of circadian rhythm
      (CR) dysregulation. Furthermore, there are hypothesized neurobiological
      mechanisms that may explain how CR dysregulation might lead to sleep, activation,
      and mood changes in unipolar and bipolar disorders. There are gaps in our
      understanding, but this paper highlights that clinical measures of sleep and
      activation are increasingly useful for monitoring the onset and course of
      affective disorders. Also, evidence suggests that CR disruptions may represent
      core elements not simply epiphenomena of affective disorders.

PMID- 21852076
TI  - Contribution of nitric oxide synthase (NOS) in blood-brain barrier disruption
      during acute focal cerebral ischemia in normal rat.
AB  - Endogenous level of nitric oxide (NO) is increased in the brain following the
      stroke, and deactivation of NO synthase has been shown to attenuate its
      destructive actions in animal stroke models using middle cerebral artery
      occlusion (MCAO) procedures. However, little is known about the effects of NO in
      cerebral vascular integrity and edema during acute cerebral ischemia. Here we
      investigated whether NO plays any role in the progression of blood-brain barrier
      (BBB) disruption and edema formation in ischemia/reperfusion injury.
      Intraperitoneal administration of NO substrate l-arginine (300mg/kg), or NOS
      inhibitor (l-NAME, 1mg/kg), was done in normal rats at 20min before a 60-min
      MCAO. Mean arterial blood pressures (MAP) and regional cerebral blood flow (rCBF)
      were continuously recorded during experiment. Neurological deficit score (NDS)
      was evaluated 12h after termination of MCAO followed with evaluations of cerebral
      infarction volume (CIV), edema formation and cerebral vascular permeability
      (CVP), as determined by the Evans blue dye extravasations (EBE) technique. No
      significant changes were observed in the values of MAP and rCBF with l-arginine
      or l-NAME during ischemia or reperfusion periods. There was a 75-85% reduction in
      rCBF in during MCAO which returned back to its pre-occlusion level during
      reperfusion. Acute cerebral ischemia with or without l-arginine augmented NDS
      (4.00+/-0.44 and 3.00+/-0.30), in conjunction with increased CIV (518+/-57mm(3)
      and 461+/-65mm(3)), provoked edema (3.09+/-0.45% and 3.30+/-0.49%), and elevated
      EBE (8.28+/-2.04MUg/g and 5.09+/-1.41MUg/g). Inhibition of NO production by l
      NAME significantly improved NDS (1.50+/-0.22), diminished CIV (248+/-56mm(3)),
      edema (1.18+/-0.58%) and EBE (1.37+/-0.12MUg/g). This study reconfirms the
      cerebroprotective properties of reduced tissue NO during acute ischemic stroke,
      and it also validates the deleterious actions of increased NOS activity on the
      disruption of cerebral microvascular integrity and edema formation of
      ischemia/reperfusion injuries in normal rat, without changing arterial blood
      pressure or blood flows to ischemic regions.

PMID- 21852077
TI  - Kernel machines for epilepsy diagnosis via EEG signal classification: a
      comparative study.
AB  - OBJECTIVE: We carry out a systematic assessment on a suite of kernel-based
      learning machines while coping with the task of epilepsy diagnosis through
      automatic electroencephalogram (EEG) signal classification. METHODS AND
      MATERIALS: The kernel machines investigated include the standard support vector
      machine (SVM), the least squares SVM, the Lagrangian SVM, the smooth SVM, the
      proximal SVM, and the relevance vector machine. An extensive series of
      experiments was conducted on publicly available data, whose clinical EEG
      recordings were obtained from five normal subjects and five epileptic patients.
      The performance levels delivered by the different kernel machines are contrasted
      in terms of the criteria of predictive accuracy, sensitivity to the kernel
      function/parameter value, and sensitivity to the type of features extracted from
      the signal. For this purpose, 26 values for the kernel parameter (radius) of two
      well-known kernel functions (namely, Gaussian and exponential radial basis
      functions) were considered as well as 21 types of features extracted from the EEG
      signal, including statistical values derived from the discrete wavelet transform,
      Lyapunov exponents, and combinations thereof. RESULTS: We first quantitatively
      assess the impact of the choice of the wavelet basis on the quality of the
      features extracted. Four wavelet basis functions were considered in this study.
      Then, we provide the average accuracy (i.e., cross-validation error) values
      delivered by 252 kernel machine configurations; in particular, 40%/35% of the
      best-calibrated models of the standard and least squares SVMs reached 100%
      accuracy rate for the two kernel functions considered. Moreover, we show the
      sensitivity profiles exhibited by a large sample of the configurations whereby
      one can visually inspect their levels of sensitiveness to the type of feature and
      to the kernel function/parameter value. CONCLUSIONS: Overall, the results
      evidence that all kernel machines are competitive in terms of accuracy, with the
      standard and least squares SVMs prevailing more consistently. Moreover, the
      choice of the kernel function and parameter value as well as the choice of the
      feature extractor are critical decisions to be taken, albeit the choice of the
      wavelet family seems not to be so relevant. Also, the statistical values
      calculated over the Lyapunov exponents were good sources of signal
      representation, but not as informative as their wavelet counterparts. Finally, a
      typical sensitivity profile has emerged among all types of machines, involving
      some regions of stability separated by zones of sharp variation, with some kernel
      parameter values clearly associated with better accuracy rates (zones of
      optimality).

PMID- 21852078
TI  - Antihyperlipidemic activity of Cassia auriculata flowers in triton WR 1339
      induced hyperlipidemic rats.
AB  - The flower extract of Cassia auriculata, herb has been used traditionally in
      India for medicinal purposes. The plant has been reported to treat hyperglycemia
      and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to
      accelerate coronary artery disease and progression of atherosclerotic lesions.
      The present work was undertaken to investigate the possible antihyperlipidemic
      and antioxidative effect of C. auriculata flower on hyperlipidemic rats.
      Hyperlipidemia was induced in rats by a single intravenous (iv) injection of
      Triton WR 1339 (300 mg/kg b.w.) and it showed sustained elevated levels of serum
      cholesterol and triglyceride. Ethanolic extract of C. auriculata flowers (Et-CAF)
      (150, 300, 450 mg/kg b.w./day) was administered to normal and hyperlipidemic rats
      for 14 days. Serum and liver tissue were analysed at three different time
      intervals for lipid profile, lipid peroxidation products, antioxidants enzymes
      and the activity were compared to the cholesterol-lowering drug, lovastatin (10
      mg/kg/b.w.). Parameters were altered during hyperlipidemia and reverted back to
      near normal values after Et-CAF treatment or standard drug lovastatin. Lipid
      peroxidation decreased whereas the activities of superoxide dismutase,
      glutathione peroxidase and catalase increased in Et-CAF treated rats. Pronounced
      changes were observed at 450 mg/kg b.w. of Et-CAF for 2 weeks and it was
      comparable to the standard drug lovastatin. The current study provides a strong
      evidence that Et-CAF has a beneficial effect in treating hyperlipidemia and ROS
      without any side effects at the dosage and duration studied.

PMID- 21852079
TI  - Interpreting mixed signals: the cell's cytokine conundrum.
AB  - Cytokines are essential for the activation, differentiation and control of the
      immune system. Many cytokines, alone or in combination with other cytokines, have
      multiple functions and can often act on many different cell types with distinct
      developmental or functional consequences. Despite the myriad of cytokines and
      cytokine receptors, there are relatively few signaling molecules that transduce
      these diverse cytokine signals. In this review, we will discuss the potential
      mechanisms used by cytokines to mediate distinct cellular outcomes from a small
      number of signaling molecules. Understanding this paradigm in cytokine signaling
      can aid in the development of potential therapeutic approaches involving cytokine
      targeting or use.

PMID- 21852081
TI  - COPD in the general population: prevalence, incidence and survival.
AB  - Worldwide, COPD is a leading cause of chronic morbidity and mortality. Although
      its prevalence is already well documented, very few studies have measured its
      incidence. We therefore investigated the prevalence, incidence and lifetime risk
      of COPD in the general population. In a population-based study including subjects
      >= 40, with 12 months of history available in the Dutch IPCI database, we
      identified COPD cases by a two-step validation algorithm. Among 185,325
      participants with 601,283 years of follow-up, 7308 subjects with COPD were
      identified, and 1713 had incident COPD. The overall IR of physician-diagnosed
      COPD was 2.92/1000PY (95%CI 2.78-3.06). The incidence of COPD was higher in men
      (3.54; 95%CI 3.33-3.77) than in women (2.34; 95%CI 2.17-2.52), and the overall
      baseline prevalence of COPD was 3.02% (95%CI 2.94-3.10). For people who had
      entered the study free of COPD at the age of 40, the risk of developing COPD
      within the next 40 years was 12.7% for men and 8.3% for women. In patients with
      very severe COPD, 26% died after 1 year of follow-up, whereas 2.8% died among the
      non-COPD subjects. In the general population in the Netherlands, three on 1000
      subjects were diagnosed with COPD per year. The incidence increased rapidly with
      age and was higher in men than in women. One in eight men and one in 12 women,
      being COPD free at the age of 40, will develop COPD during their further life.
      Mortality rates differed substantially between COPD patients and non-COPD
      subjects of the same age, underlining the burden of this disease.

PMID- 21852080
TI  - Recent advances in the IL-17 cytokine family.
AB  - The IL-17/IL-17 receptor family is the newest and least understood of the
      cytokine subclasses. Composed of ligands IL-17A-IL-17F and receptors IL-17RA-IL
      17RE, these cytokines have many unique structural and functional features. Since
      the discovery of the 'Th17' subset in 2005, particular attention has been paid to
      IL-17A and IL-17F and their cognate receptors. To date, far less is known about
      the rest of the family. This review discusses recent advances in the field, with
      an emphasis on IL-17A biology.

PMID- 21852082
TI  - High-fat diets rich in soy or fish oil distinctly alter hypothalamic insulin
      signaling in rats.
AB  - Hypothalamic insulin inhibits food intake, preventing obesity. High-fat feeding
      with polyunsaturated fats may be obesogenic, but their effect on insulin action
      has not been elucidated. The present study evaluated insulin hypophagia and
      hypothalamic signaling after central injection in rats fed either control diet
      (15% energy from fat) or high-fat diets (50% energy from fat) enriched with
      either soy or fish oil. Soy rats had increased fat pad weight and serum leptin
      with normal body weight, serum lipid profile and peripheral insulin sensitivity.
      Fish rats had decreased body and fat pad weight, low leptin and corticosterone
      levels, and improved serum lipid profile. A 20-mU dose of intracerebroventricular
      (ICV) insulin inhibited food intake in control and fish groups, but failed to do
      so in the soy group. Hypothalamic protein levels of IR, IRS-1, IRS-2, Akt, mTOR,
      p70S6K and AMPK were similar among groups. ICV insulin stimulated IR tyrosine
      phosphorylation in control (68%), soy (36%) and fish (34%) groups. Tyrosine
      phosphorylation of the pp185 band was significantly stimulated in control (78%)
      and soy (53%) rats, but not in fish rats. IRS-1 phosphorylation was stimulated
      only in control rats (94%). Akt serine phosphorylation was significantly
      stimulated only in control (90%) and fish (78%) rats. The results showed that,
      rather than the energy density, the fat type was a relevant aspect of high-fat
      feeding, since blockade of hypothalamic insulin signal transmission and insulin
      hypophagia was promoted only by the high-fat soy diet, while they were preserved
      in the rats fed with the high-fat fish diet.

PMID- 21852083
TI  - Effects of long-term consumption of low doses of resveratrol on diet-induced mild
      hypercholesterolemia in pigs: a transcriptomic approach to disease prevention.
AB  - Metabolic and cardiovascular diseases (CVDs) have risen to alarming proportions,
      and there is a need for therapeutic and preventive measures. The polyphenol
      resveratrol (RES) protects against CVDs, but in vivo molecular mechanisms
      responsible for protection are not yet understood. Peripheral blood mononuclear
      cells (PBMNCs) are involved in the development of atherosclerosis and metabolic
      disorders. The identification of PBMNCs genes responding to dietary compounds
      might help to understand the mechanisms underlying the effects of polyphenols. We
      determined gene expression differences between PBMNCs from pigs fed a high-fat
      diet manifesting a mild increase of cholesterol and pigs fed a high-fat diet
      containing low doses of RES. Although the consumption of RES did not modify the
      levels of cholesterol, microarray analyses indicated that some of the
      differentially expressed genes, collagens (COL1A, COL3A), lipoprotein lipase
      (LPL) and fatty-acid binding proteins (FABPs) involved in CVDs and lipid
      metabolism were up-regulated by the high-fat diet and down-regulated by RES.
      Reverse transcriptase polymerase chain reaction confirmed that RES and RES
      containing grape extract prevented the induction of FABP4 in PBMNCs in female
      pigs fed a high-fat diet. Low micromolar concentrations of RES and its metabolite
      dihydroresveratrol exerted a minor but significant reducing effect on the
      induction of FABP4 expression in human macrophages treated with oxidized low
      density lipoprotein. Our results show that the consumption of low doses of RES
      modulates the expression of genes related to lipid metabolism and metabolic
      disorders that are affected by a high-fat diet and suggest that some of the
      circulating RES metabolites may contribute to these effects.

PMID- 21852084
TI  - N-3 polyunsaturated fatty acid consumption produces neurobiological effects
      associated with prevention of depression in rats after the forced swimming test.
AB  - Epidemiological data and clinical trials suggest that n-3 polyunsaturated fatty
      acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have
      preventive and therapeutic effects on depression; however, the underlying
      mechanism remains elusive. The present study aimed to examine the behavioral
      effects and antidepressant mechanism of n-3 PUFA using a forced swimming test.
      Eleven-week-old male Sprague-Dawley rats were fed an American Institute of
      Nutrition-93M diet containing 0%, 0.5% or 1% EPA and DHA relative to the total
      energy intake in their diet for 12 weeks (n=8 per group). Total dietary intake,
      body weight and hippocampus weights were not significantly different among
      groups. The groups administered 0.5% and 1% EPA+DHA diets had significantly
      higher levels of n-3 PUFA in their brain phospholipids compared to those in the
      control group. The immobility time was significantly decreased and the climbing
      time was significantly increased in the 0.5% and 1% EPA+DHA groups compared with
      those in the 0% EPA+DHA group. Plasma serotonin concentration and hippocampus c
      AMP response element binding protein (CREB) expression were significantly
      increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA
      group. Conversely, interleukin (IL)-6 expression was significantly reduced in the
      0.5% and 1% EPA+DHA groups compared with that in the 0% EPA+DHA group. However,
      there were no dose-dependent effects of n-3 PUFA and no significant differences
      in expressions of IL-1beta, tumor necrosis factor-alpha, brain-derived
      neurotrophic factor or phosphorylated CREB. In conclusion, long-term intake of
      EPA+DHA induced antidepressant-like effects in rats and overexpression of CREB
      via decreased IL-6 expression.

PMID- 21852086
TI  - gamma-Tocotrienol inhibits cell viability through suppression of beta-catenin/Tcf
      signaling in human colon carcinoma HT-29 cells.
AB  - gamma-Tocotrienol, a major component of the tocotrienol-rich fraction of palm
      oil, has been suggested to have antioxidant and anticancer activity as well as
      potent chemopreventive effects on tumor cells. In this study, the mechanisms
      underlying gamma-tocotrienol-mediated growth inhibition of human carcinoma HT-29
      cells were further investigated, especially in correlation with the involvement
      of beta-catenin/T-cell factor (Tcf) signaling pathway. We found that gamma
      tocotrienol could strongly suppress the transcriptional activity of beta
      catenin/Tcf signaling pathway in HT-29 cells. gamma-Tocotrienol inhibited the
      expression level of total beta-catenin protein but did not significantly affect
      the phosphorylated beta-catenin level. Meanwhile, gamma-tocotrienol down
      regulated the protein level of nuclear beta-catenin and induced its
      redistribution to cell membrane. Furthermore, gamma-tocotrienol suppressed the
      expression of downstream target genes such as c-myc, cyclin D1 and survivin. The
      results demonstrated that gamma-tocotrienol-inhibited growth and -induced
      apoptosis in HT-29 cells were accompanied by significant inhibition of beta
      catenin/Tcf signaling. Blocking the expression of beta-catenin with small
      interfering RNA significantly suppressed the ability of gamma-tocotrienol to
      reduce viability and induce apoptosis in HT-29 cells. Thus, our data suggested
      that gamma-tocotrienol exerts its anticancer activity through beta-catenin/Tcf
      signaling, and beta-catenin is a target for gamma-tocotrienol in the Wnt/beta
      catenin signaling pathway.

PMID- 21852085
TI  - DHA reduces the atrophy-associated Fn14 protein in differentiated myotubes during
      coculture with macrophages.
AB  - Macrophages are an important component of muscle where they are involved in
      complex processes such as repair, regeneration and hypertrophy. We recently
      reported that macrophage numbers increase in the muscle of obese patients,
      suggesting that muscle-resident macrophages could be involved in the development
      of muscle insulin resistance that is associated with obesity. Coculture of
      activated macrophages with human muscle cells impairs insulin signaling and
      induces atrophy signaling pathways in the human muscle cells; this is exacerbated
      by the addition of palmitic acid. In this study, we tested the hypothesis that
      docosahexaenoic acid (DHA), a polyunsaturated fatty acid that has anti
      inflammatory properties, would have the opposite effect of palmitic acid on
      muscle-macrophage cocultures. Surprisingly, DHA did not stimulate insulin
      signaling in human muscle myotubes that were cocultured with fibroblasts or
      macrophages. However, DHA inhibited Fn14, the TNF-like weak inducer of apoptosis
      receptor that increases the expression of the muscle-specific ubiquitin ligase
      MuRF-1 (muscle ring-finger protein-1). DHA treatment also increased the apparent
      molecular mass of MuRF-1 on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis gels, suggesting that DHA causes MuRF-1 to be posttranslationally
      modified. In conclusion, these results suggest that DHA may have a beneficial
      effect on muscle mass in humans by inhibiting the induction of Fn14 by
      infiltrating macrophages.

PMID- 21852087
TI  - Dietary apigenin regulates high glucose and hypoxic reoxygenation-induced
      reductions in apelin expression in human endothelial cells.
AB  - The early stages of vascular endothelial dysfunction enhance angiogenic
      stimulation and strongly influence vascular rearrangement. The aim of this study
      was to determine whether a short period of high glucose (HG, 30 mM glucose) plus
      tumor necrosis factor alpha (TNFalpha) treatment or reoxygenation after hypoxia
      (H/R) alters the expression levels of apelin in human endothelial cells. In
      addition, we also examined the effects of the dietary flavonoid apigenin on
      apelin expression. Human endothelial cell lines were treated with HG plus
      TNFalpha or subjected to H/R. The expression levels of genes and proteins were
      then assessed by the reverse transcriptase polymerase chain reaction, Western
      blotting and immunofluorescence analyses. The expression level of apelin was
      significantly higher in the HG group following exposure to reoxygenation or
      TNFalpha. Reoxygenation after hypoxia decreased the expression levels of apelin
      and fatty acid transport protein (FATP) 1 compared with those observed during
      hypoxia alone and normoxia in a normal glucose concentration. Inversely, apigenin
      augmented H/R-reduced apelin and FATP1 expression in endothelial cells. Based on
      our findings, we propose that the early stages of endothelial disorder subtly
      influence angiogenesis and that HG and H/R stimulate vascular rearrangement and
      are involved in fatty acid uptake. Furthermore, dietary apigenin might improve
      the expression of angiogenic genes and fatty acid uptake.

PMID- 21852088
TI  - Damnacanthal, a noni component, exhibits antitumorigenic activity in human
      colorectal cancer cells.
AB  - Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda
      citrifolia L. (noni), which has been used for traditional therapy in several
      chronic diseases including cancer. Although noni has been consumed for a long
      time in Asian and Polynesian countries, the molecular mechanisms by which it
      exerts several benefits are starting to emerge. In this report, we examined
      systematic approaches on the cancer-suppressing capability of damnacanthal in
      colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as
      caspase activity induction in colorectal cancer cells. We also examined several
      potential target proteins and found that the proapoptotic protein nonsteroidal
      anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we
      have found that damnacanthal also enhances transcription factor CCAAT/enhancer
      binding protein beta (C/EBPbeta), which controls NAG-1 transcriptional activity.
      Blocking of C/EBPbeta by shRNA results in the reduction of NAG-1 expression as
      well as caspase activity in the presence of damnacanthal. Taken together, these
      results indicate that damnacanthal increases antitumorigenic activity in human
      colorectal cancer cells and that C/EBPbeta plays a role in damnacanthal-induced
      NAG-1 expression.

PMID- 21852089
TI  - Caloric restriction increases adiponectin expression by adipose tissue and
      prevents the inhibitory effect of insulin on circulating adiponectin in rats.
AB  - Aging is associated with redistribution of body fat and the development of
      insulin resistance. White adipose tissue emerges as an important organ in
      controlling life span. Caloric restriction (CR) delays the rate of aging possibly
      modulated partly by altering the amount and function of adipose tissue.
      Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and
      insulin-sensitizing properties. This study examined the effects of CR on
      adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2)
      in adipose tissue and in isolated adipocytes of Brown Norway rats that had
      undergone CR for 4 months or fed ad libitum. The study also determined plasma
      concentrations of adiponectin and insulin in these animals and whether insulin
      infusion for 7 days affects adiponectin expression and its circulating
      concentrations under CR conditions. CR markedly reduced body weight as
      anticipated, epididymal fat mass and adipocyte size. CR led to an increase in
      plasma free fatty acid and glycerol (both twofold), and adipose triglyceride
      lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2
      fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes
      (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats.
      However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression.
      Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but
      did not reverse the CR-induced up-regulation of circulating adiponectin levels.
      Our results suggest that the benefits of CR could be, at least in part, dependent
      on enhanced expression and secretion of adiponectin by adipocytes.

PMID- 21852090
TI  - Henceforth harm reduction?

PMID- 21852091
TI  - The term and the vision.

PMID- 21852092
TI  - The policymaker's Hippocratic oath.

PMID- 21852094
TI  - Harm reduction is not enough for supply side policy: a human rights-based
      approach offers more.

PMID- 21852093
TI  - Short-term safety of buprenorphine/naloxone in HIV-seronegative opioid-dependent
      Chinese and Thai drug injectors enrolled in HIV Prevention Trials Network 058.
AB  - BACKGROUND: Buprenorphine/naloxone (BUP/NX) is not licenced for use in China or
      Thailand and there was little clinical experience with this drug combination in
      these countries at the inception of HIV Prevention Trial Network (HPTN) 058, a
      randomized trial comparing risk reduction counselling combined with either short
      term or long-term medication assisted treatment with BUP/NX to prevent HIV
      infection and death amongst opioid-dependent injectors. METHODS: We conducted a
      safety phase that included the first 50 subjects enrolled at each of the three
      initial study sites (N=150). Clinical and laboratory assessments were conducted
      at baseline and weekly for the first 4 weeks. Changes in laboratory parameters
      were estimated with random effects models. RESULTS: BUP/NX was well tolerated by
      study subjects and opioid withdrawal scores decreased substantially during the 3
      day induction. Two participants experienced grade 3 clinical adverse events,
      which were categorized as probably not related to the study drug. Grade 2 or 3
      increases in alanine aminotransferase (ALT) occurred in 25 (17%) subjects. The
      magnitude of ALT increase over 4-week follow-up was strongly associated with
      baseline ALT elevation. CONCLUSIONS: In Chinese and Thai opioid-dependent
      injectors, we found BUP/NX to be effective in reducing opioid withdrawal symptoms
      and safe during short-term use. ALT increases were observed over 4-week-follow
      up, which are consistent with reports from Western populations. Long-term safety
      and efficacy evaluations are indicated.

PMID- 21852095
TI  - Harm reduction for the supply-side: its time has come.

PMID- 21852096
TI  - Where harm reduction meets housing first: exploring alcohol's role in a project
      based housing first setting.
AB  - BACKGROUND: Housing first (HF) programmes provide low-barrier, nonabstinence
      based, immediate, supportive and permanent housing to chronically homeless people
      who often have co-occurring substance-use and/or psychiatric disorders. Project
      based HF programmes offer housing in the form of individual units within a larger
      housing project. Recent studies conducted at a specific project-based HF
      programme that serves chronically homeless individuals with alcohol problems
      found housing provision was associated with reduced publicly funded service
      utilisation, decreased alcohol use, and sizable cost offsets. No studies to date,
      however, have qualitatively explored the role of alcohol use in the lives of
      residents in project-based HF. METHODS: We collected data in a project-based HF
      setting via naturalistic observation of verbal exchanges between staff and
      residents, field notes taken during staff rounds, and audio recorded staff focus
      groups and resident interview sessions. Qualitative data were managed and coded
      using a constant comparative process consistent with grounded theory methodology.
      The goal of the analysis was to generate a conceptual/thematic description of
      alcohol's role in residents' lives. RESULTS: Findings suggest it is important to
      take into account residents' motivations for alcohol use, which may include
      perceived positive and negative consequences. Further, a harm reduction approach
      was reported to facilitate housing attainment and maintenance. Residents and
      staff reported that traditional, abstinence-based approaches are neither
      desirable nor effective for this specific population. Finally, elements of the
      moral model of alcohol dependence continue to pervade both residents' views of
      themselves and the community's perceptions of them. CONCLUSIONS: Findings suggest
      it is necessary to set aside traditional models of alcohol use and approaches to
      better understand, align with, and address this population's needs. In doing so,
      we might gain further insights into how to enhance the existing project-based HF
      approach by applying more tailored, alcohol-specific, harm reduction
      interventions.

PMID- 21852097
TI  - Switzerland, HIV and the power of pragmatism: lessons for drug policy
      development.
AB  - Switzerland in the 1980s was an epicentre of HIV as open drug injection became
      part of the urban scene, especially in Zurich. Cracks appeared in Switzerland's
      long commitment to policing as the main drug-control strategy as law enforcement
      was unable to contain the health and social consequences of the rapid spread of
      drug injection. In the early stages of the epidemic, the pioneering health care
      providers who brought technically illegal harm reduction services into the open
      drug scene in Zurich helped open the exploration at the federal level of more
      balanced drug policy. Carefully evaluated pilot experiences in low-threshold
      methadone, needle exchange, and eventually heroin-assisted therapy yielded
      evidence of significant HIV prevention and crime reduction that was convincing
      not only to policy-makers but also to a skeptical Swiss public. Whilst not all
      countries have Switzerland's resource base, the Swiss experience still holds many
      useful lessons for establishing evidence-based policy on illicit drugs.

PMID- 21852098
TI  - Measuring drug law enforcement--from process to outcomes.

PMID- 21852099
TI  - Model calibration and validation for OFMSW and sewage sludge co-digestion
      reactors.
AB  - A mathematical model has recently been proposed by the authors to simulate the
      biochemical processes that prevail in a co-digestion reactor fed with sewage
      sludge and the organic fraction of municipal solid waste. This model is based on
      the Anaerobic Digestion Model no. 1 of the International Water Association, which
      has been extended to include the co-digestion processes, using surface-based
      kinetics to model the organic waste disintegration and conversion to
      carbohydrates, proteins and lipids. When organic waste solids are present in the
      reactor influent, the disintegration process is the rate-limiting step of the
      overall co-digestion process. The main advantage of the proposed modeling
      approach is that the kinetic constant of such a process does not depend on the
      waste particle size distribution (PSD) and rather depends only on the nature and
      composition of the waste particles. The model calibration aimed to assess the
      kinetic constant of the disintegration process can therefore be conducted using
      organic waste samples of any PSD, and the resulting value will be suitable for
      all the organic wastes of the same nature as the investigated samples,
      independently of their PSD. This assumption was proven in this study by
      biomethane potential experiments that were conducted on organic waste samples
      with different particle sizes. The results of these experiments were used to
      calibrate and validate the mathematical model, resulting in a good agreement
      between the simulated and observed data for any investigated particle size of the
      solid waste. This study confirms the strength of the proposed model and
      calibration procedure, which can thus be used to assess the treatment efficiency
      and predict the methane production of full-scale digesters.

PMID- 21852100
TI  - Overcoming the fear of waste.

PMID- 21852101
TI  - A new biosensor for glucose determination in serum based on up-converting
      fluorescence resonance energy transfer.
AB  - In this work, a new glucose sensor based on up-converting fluorescence resonance
      energy transfer (UC-FRET) was developed. Up-converting phosphors (UCPs, NaYF(4):
      Yb, Er), which were covalently labeled with Concanavalin A (ConA), were used as
      the energy donor with thiolated beta-cyclodextrins (SH-beta-CDs) functionalized
      gold nanoparticles as the energy acceptor. Due to the combination between ConA
      and SH-beta-CDs, the energy donor and the acceptor were brought to close
      proximity, resulting in the quenching of the fluorescence of UCPs by gold
      nanoparticles. In the presence of glucose which competed with SH-beta-CDs towards
      the binding sites of ConA, the biosensor (UCPs-ConA-SH-beta-CDs-Au) was
      decomposed and the energy donor was separated from the acceptor. Therefore, the
      fluorescence of UCPs was restored dependent on the concentration of glucose. The
      increase of UCPs fluorescence intensity was proportional to glucose concentration
      within the range from 0.4 MUM to 10MUM in aqueous buffer, with a limit of
      detection (LOD) of 0.043 MUM. A same linear range of glucose concentration was
      obtained in a human serum matrix (which was pretreated and thus contained no
      glucose) with a slightly higher LOD (0.065 MUM). The glucose sensor was applied
      to real human serum samples with the results consistent with that of a classic
      hexokinase (HK) method, indicating that the UC-FRET biosensor was competent for
      directly sensing glucose in serum samples without optical interference, which
      benefited from the near infrared (NIR) excitation nature of UCPs. The results of
      this work suggested that the UC-FRET technique could be a promising alternative
      for detecting biomolecules in complex biological sample matrixes for diagnostic
      purposes.

PMID- 21852102
TI  - Detection of ricin using a carbon nanofiber based biosensor.
AB  - We report ricin detection using antibody and aptamer probes immobilized on a
      nanoelectrode array (NEA) consisting of vertically aligned carbon nanofibers
      (VACNFs). These biosensor chips are fabricated on a wafer scale using steps
      common in integrated circuit manufacturing. Electrochemical impedance
      spectroscopy is used to characterize the detection event and the results indicate
      that the electron transfer resistance changes significantly after the ricin
      protein binds to the probe. Further confirmation is obtained from evaluation of
      the electrode surface by atomic force microscopy which clearly shows a change in
      height from the bare electrode to the surface bound by the probe-protein.

PMID- 21852103
TI  - A novel NiO-Au hybrid nanobelts based sensor for sensitive and selective glucose
      detection.
AB  - A novel amperometric nonenzymatic glucose sensor based on Au-doped NiO nanobelts
      has been successfully fabricated and applied to nonenzymatic glucose detection.
      Its electrochemical behavior towards the oxidation of glucose was compared with
      NiO nanofibers and Au microparticles prepared with a similar procedure. The NiO
      Au hybrid nanobelts modified electrode displays greatly enhanced electrocatalytic
      activity towards glucose oxidation, revealing a synergistic effect between the
      matrix NiO and the doped Au. The as-prepared NiO-Au nanobelts based glucose
      sensor displays significantly lower onset potential, lower detection limit,
      higher sensitivity, and wider linear range than that of pristine NiO nanofibers
      modified electrode. Moreover, Au nanoparticles distributed in NiO nanofibers
      enabled amperometric glucose detection with insignificant interference from
      ascorbic acid and uric acid. These results indicate that the NiO-Au hybrid
      nanobelt is a promising candidate in the development of highly sensitive and
      selective nonenzymatic glucose sensors.

PMID- 21852104
TI  - A disposable bio-nano-chip using agarose beads for high performance immunoassays.
AB  - This article reports on the fabrication of a disposable bio-nano-chip (BNC), a
      microfluidic device composed of polydimethylsiloxane (PDMS) and thiolene-based
      optical epoxy which is both cost-effective and suitable for high performance
      immunoassays. A novel room temperature (RT) bonding technique was utilized so as
      to achieve irreversible covalent bonding between PDMS and thiolene-based epoxy
      layers, while at the same time being compatible with the insertion of agarose
      bead sensors, selectively arranged in an array of pyramidal microcavities
      replicated in the thiolene thin film layer. In the sealed device, the bead
      supporting epoxy film is sandwiched between two PDMS layers comprising of fluidic
      injection and drain channels. The agarose bead sensors used in the device are
      sensitized with anti-C-reactive protein (CRP) antibody, and a fluorescent
      sandwich-type immunoassay was run to characterize the performance of this device.
      Computational fluid dynamics (CFD) was used based on the device specifications to
      model the bead penetration. Experimental data revealed analyte penetration of the
      immunocomplex to 100 MUm into the 280 MUm diameter agarose beads, which
      correlated well with the simulation. A dose-response curve was obtained and the
      linear dynamic range of the assay was established over 1 ng/mL to 50 ng/mL with a
      limit of detection less than 1 ng/mL.

PMID- 21852105
TI  - Characterization and application of a surface modification designed for QCM-D
      studies of biotinylated biomolecules.
AB  - The rapid development of surface sensitive biosensor technologies, especially
      towards nanoscale devices, requires increasing control of surface chemistry to
      provide reliable and reproducible results, but also to take full advantage of the
      sensing opportunities. Here, we present a surface modification strategy to allow
      biotinylated biomolecules to be immobilized to gold coated sensor crystals for
      quartz crystal microbalance with dissipation monitoring (QCM-D) sensing. The
      unique feature of QCM-D is its sensitivity to nanomechanical (viscoelastic)
      properties at the sensing interface. The surface modification was based on mixed
      monolayers of oligo(ethylene glycol) (OEG) disulfides, with terminal -OH or
      biotin groups, on gold. Mixtures containing 1% of the biotin disulfide were
      concluded to be the most appropriate based on the performance when streptavidin
      was immobilized to biotinylated sensors and the subsequent biotinylated bovine
      serum albumin (BSA) interaction was studied. The OEG background kept the
      unspecific protein binding to a minimum, even when subjected to serum solutions
      with a high protein concentration. Based on characterization by contact angle
      goniometry, ellipsometry, and infrared spectroscopy, the monolayers were shown to
      be well-ordered, with the OEG chains predominantly adopting a helical
      conformation but also partly an amorphous structure. Storage stability was
      concluded to depend mainly on light exposure while almost all streptavidin
      binding activity was retained when storing the sensors cold and dark for 8 weeks.
      The surface modification was also tested for repeated antibody-antigen
      interactions between BSA and anti-BSA (immobilized to biotinylated protein A) in
      QCM-D measurements lasting for >10h with intermediate basic regeneration. This
      proved an excellent stability of the coating and good reproducibility was
      obtained for 5 interaction cycles. With this kind of generic surface modification
      QCM-D can be used in a variety of biosensing applications to provide not only
      mass but also relevant information of the structural properties of adlayers.

PMID- 21852106
TI  - Hemodynamic effects of a right lumbar-pelvic wedge during spinal anesthesia for
      cesarean section.
AB  - BACKGROUND: Aortocaval compression is a major cause of maternal hypotension. A
      randomized controlled trial was designed to determine the effectiveness of a
      mechanical intervention using a right lumbar-pelvic wedge in preventing
      hypotension after spinal anesthesia for cesarean delivery. METHODS: Eighty
      healthy women undergoing elective cesarean section were randomly allocated
      immediately after spinal blockade to either a lumbar-pelvic wedge positioned
      under the right posterior-superior iliac crest (Wedge group, n=40) or the
      complete supine position (Supine group, n=40). Hemodynamic values, vasopressor
      consumption and adverse effects were collected during the surgical procedure.
      Hypotension was defined as a reduction in systolic blood pressure of 25% from
      baseline. Patient allocation, management and data collection were performed by a
      single unblinded anesthetist. RESULTS: There was no difference in the incidence
      of hypotension between the two groups (42.5% vs. 50%, P=0.51). During the first 5
      min, blood pressure decreased less in the Wedge group. There were significant
      differences in median [interquartile range] vasopressor requirements between the
      Wedge group and the Supine group (1 [0-2] vs. 3 [1-4] mg, P<0.01) and in nausea
      during the procedure (6 vs. 22 patients, P<0.01). CONCLUSION: In our study
      population the use of right lumbar-pelvic wedge was not effective in reducing the
      incidence of hypotension during spinal anesthesia for cesarean section. Patients
      in whom the wedge was used had higher systolic blood pressure values during the
      first 5 min of anesthesia and fewer episodes of nausea. The risk of hypotension
      remains substantial.

PMID- 21852107
TI  - Role of prophylactic uterine artery balloon catheters in the management of women
      with suspected placenta accreta.
AB  - BACKGROUND: Placenta praevia and accreta are leading causes of major obstetric
      haemorrhage and peripartum hysterectomy. Detection is largely based on a high
      index of clinical suspicion, though the diagnostic accuracy of radiological
      imaging is improving. Interventional radiological techniques can reduce blood
      loss and the incidence of hysterectomy. METHODS: We have reviewed our experience
      with bilateral prophylactic uterine artery balloon occlusion in the management of
      women with suspected placenta accreta. Thirteen women at high risk of major
      haemorrhage due to placenta praevia or suspected placenta accreta were
      retrospectively studied. Uterine artery balloons were placed prophylactically
      under neuraxial anaesthesia in the angiography suite followed by caesarean
      delivery in the obstetric operating theatre. RESULTS: Intraoperative blood loss
      and transfusion requirements were low in our case series. There were no
      hysterectomies or admissions to the intensive care unit. Fetal bradycardia
      necessitating immediate caesarean delivery occurred in two women (15.4%).
      CONCLUSION: In our case series in women with suspected placenta accreta,
      prophylactic use of uterine artery balloons was associated with a low requirement
      for blood transfusion but with possible increased risk of fetal compromise.
      Performing the interventional procedure at a different site from the operative
      room complicated management.

PMID- 21852108
TI  - Complex expression patterns of Eph receptor tyrosine kinases and their ephrin
      ligands in colorectal carcinogenesis.
AB  - Aberrant expression of Eph and ephrin proteins in human cancers is extensively
      documented. However, data are frequently limited to one gene and therefore
      incomplete and in some instances conflicting. We analysed expression of all Eph
      and ephrin genes in colorectal cancer (CRC) cell lines and 153 clinical
      specimens, providing for the first time a comprehensive analysis of this system
      in CRC. Eph/ephrin mRNA expression was assessed by quantitative real-time PCR and
      correlated with protein expression (flow cytometry, Western blotting and
      immunocytochemistry). These data show that EphA1, EphA2, EphB2 and EphB4 were
      significantly over expressed in CRC. In all cases, at least one Eph gene was
      found in normal colon (EphA1, EphA2, EphB2, EphB4), where expression was observed
      at high levels in most CRCs. However, other Eph gene expression was lost in
      individual CRCs compared to the corresponding normal, EphA7 being a striking
      example. Loss of expression was more common in advanced disease and thus
      correlated with poor survival. This is consistent with the redundant
      functionality of Eph receptors, such that expression of a single Eph gene is
      sufficient for effector function. Overall, the data suggest a progressive loss of
      expression of individual Eph genes suggesting that individual CRCs need to be
      phenotyped to determine which Eph genes are highly expressed. Targeted therapies
      could then be selected from a group of specific antibodies, such as those
      developed for EphA1.

PMID- 21852109
TI  - EGFR gene copy number alteration is a better prognostic indicator than protein
      overexpression in oral tongue squamous cell carcinomas.
AB  - Although epidermal growth factor receptor (EGFR) is particularly important in the
      pathogenesis of head and neck squamous cell carcinomas (HNSCCs), conflicting data
      have been reported on the correlation between EGFR copy number and survival and
      the association between EGFR copy number and protein expression. Anatomical site
      of the tumour in HNSCCs may likely contribute to the discordance of the above
      points as EGFR expression may differ between the sub-sites of HNSCCs. Thus, in
      this study, we focused on oral tongue squamous cell carcinomas (OTSCCs). To
      investigate the association between EGFR copy number alteration and
      overexpression and to determine which is the more reliable prognostic indicator,
      Fluorescence in situ hybridisation (FISH) and immunohistochemical staining (IHC)
      were performed at a single institution on samples from 89 patients with OTSCCs
      undergoing surgery as the primary treatment modality. Thirty-two (36%) of 89
      cases demonstrated an EGFR copy number alteration. EGFR protein expression was
      found in all 89 cases, of which 82.0% showed overexpression. No significant
      correlation was found between gene copy number and protein overexpression. Gene
      copy number alteration was significantly associated with reduced disease-free
      survival (P=0.048) and overall survival (P=0.001). Multivariate Cox proportional
      hazards analysis demonstrated that EGFR copy number increase was significantly
      correlated with overall survival (P=0.001). EGFR copy number status is a more
      reliable indicator than protein overexpression of the survival rate in OTSCCs.
      FISH analysis of the EGFR status is useful in predicting poor prognosis in
      OTSCCs.

PMID- 21852110
TI  - CA125 (MUC16) gene silencing suppresses growth properties of ovarian and breast
      cancer cells.
AB  - The tumour-associated antigen CA125 (mucin 16, MUC16) is commonly expressed in
      ovarian cancer, and can also be detected in other tumour of epithelial origin,
      but its physiological role is largely unknown. The aim of the present study was
      to investigate the impact of MUC16 gene silencing on the growth properties of
      ovarian and breast cancer cells. We analysed cellular effects linked to
      oncogenesis, such as proliferation, cell cycle and apoptosis, after transient and
      stable transfection with MUC16 short hairpin RNA (shRNA) in diverse epithelial
      cancer cell lines with different MUC16 expression. Furthermore, alterations in
      cell adhesion, migration and invasion were evaluated in stable MUC16 knockdown
      clones. The growth of all tested MUC16(+) tumour cells was significantly
      suppressed by induction of caspase-dependent apoptosis after transient
      transfection with MUC16 shRNA, irrespective of the initial MUC16 expression level
      and cancer origin. Growth inhibition could be confirmed in stable MUC16 knockdown
      clones, albeit caspase-dependent death pathways seemed no longer be activated. In
      MUC16(low+) ovarian cancer cells, stable MUC16 gene silencing resulted in a
      substantial blockade of colony formation, cell adhesion, migration and
      invasiveness associated with reduced activation of metalloproteinases-2 (MMP-2).
      By contrast, the tested MUC16(high+) cell lines displayed a non-motile and non
      invasive phenotype which was not affected by MUC16 knockdown, probably due to the
      expression of different MUC16 isoforms with divergent functions in individual
      cell lines. Our results provide evidence for a central role of MUC16 in cancer
      cell survival pathways. Additionally, MUC16 might also be involved in adhesion,
      migration and invasion depending on the type of cancer cell.

PMID- 21852111
TI  - Case-control study of shift-work and breast cancer risk in Danish nurses: impact
      of shift systems.
AB  - BACKGROUND: Working outside normal daytime hours is increasing worldwide and is
      now one of the most widespread potential carcinogenic occupational exposures.
      There is sufficient evidence in experimental animals that light exposure during
      the biologic night increases tumour growth and limited epidemiologic evidence
      that night shift-work cause breast cancer. Existing studies had crude definitions
      of shift-work and did not discriminate between shift-work systems (e.g. permanent
      versus rotating or evening versus night). METHODS: We performed an interview
      based nested case-control study within a nationwide cohort of Danish nurses,
      including detailed information on lifetime shift-work and potential confounders.
      Cases of primary breast cancer (n=310) were identified from the nationwide Danish
      Cancer Registry. Four control nurses were selected for each case by incidence
      density sampling. Odds rations (ORs) and 95% confidence intervals (CIs) were
      estimated by conditional logistic regression, with adjustment for potential
      confounders. FINDINGS: Overall, nurses who worked rotating shifts after midnight
      had a significantly increased OR (1.8; CI 1.2-2.8) for breast cancer compared to
      nurses with permanent day work. No association was found in a small group of
      nurses with evening work and no night work (OR=0.9; 0.4-1.9). The subgroup of
      nurses with periods of permanent night shift in addition to rotating night and
      day shifts experienced an OR of 2.9 (1.1-8.0). For nurses working after midnight
      compared to nurses never ending work before midnight, OR in the third tertile of
      cumulative number of shifts was 2.2 (1.5-3.2). In an analysis of different
      rotating shift systems, the highest OR (2.6; 1.8-3.8) was observed for long-term
      day-night rotating shifts. INTERPRETATION: The results provide further evidence
      that night shift-work may increase the risk for breast cancer and suggest that
      the largest impact on risk is associated with the most disruptive shifts.
      FUNDING: Danish Cancer Society and National Programme of Environmental Health
      Research.

PMID- 21852112
TI  - EW-7195, a novel inhibitor of ALK5 kinase inhibits EMT and breast cancer
      metastasis to lung.
AB  - Recently, researchers are actively pursuing efforts to develop potent and
      selective ALK5 (TbetaRI) kinase inhibitors for clinical development. In this
      study, the authors examined a novel small molecule inhibitor of ALK5, 3-((4
      ([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2
      yl)methylamino)benzonitrile (EW-7195) to determine if it has potential for cancer
      treatment. The inhibitory effects of EW-7195 on TGF-beta-induced Smad signaling
      and epithelial-to-mesenchymal transition (EMT) were investigated in mammary
      epithelial cells using luciferase reporter assays, immunoblotting, confocal
      microscopy and wound healing assays. In addition, the suppressive effects of EW
      7195 on mammary cancer metastasis to lung were examined using a Balb/c xenograft
      and MMTV/cNeu transgenic mice model system. The novel ALK5 inhibitor, EW-7195,
      inhibited the TGF-beta(1)-stimulated transcriptional activations of p3TP-Lux and
      pCAGA(12)-Luc. In addition, EW-7195 decreased phosphorylated Smad2 levels and the
      nuclear translocation of Smad2 increased by TGF-beta(1). In addition, EW-7195
      inhibited TGF-beta(1)-induced EMT and wound healing of NMuMG cells. Furthermore,
      in xenografted Balb/c and MMTV/cNeu mice, EW-7195 inhibited metastasis to lung
      from breast tumours. The novel ALK5 inhibitor, EW-7195, efficiently inhibited TGF
      beta(1)-induced Smad signaling, EMT and breast tumour metastasis to the lung in
      vivo, demonstrating that EW-7195 has therapeutic potential for the breast cancer
      metastasis to the lung.

PMID- 21852113
TI  - Differences according to socioeconomic status in the management and mortality in
      men with high risk prostate cancer.
AB  - BACKGROUND: Outcomes for many cancer forms are associated with socioeconomic
      status (SES).We investigated if SES was associated with management and mortality
      in men with high risk prostate cancer. MATERIAL AND METHODS: A nation-wide
      population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged
      database including data on incident prostate cancer identified in the National
      Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined
      as T3 tumour, and/or Gleason score 8-10 and/or PSA 20-50 ng/mL. Use of bone scan,
      curative treatment, and mortality in relation to SES was assessed by logistic,
      Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR
      and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period
      and clinical subgroups. RESULTS: Amongst 17,522 high risk prostate cancer
      patients, a bone scan was more often performed in higher white-collar than in
      blue-collar workers (OR 1.30; 95% CI 1.21-1.40). Amongst men without metastases,
      the likelihood of intention to treat was higher in higher white-collar workers
      (OR 1.43; 95% CI 1.28-1.57). In men who received curative treatment, the
      likelihood was higher to undergo radical prostatectomy for higher white-collar
      patients (OR 1.29; 95% CI 1.10-1.47). In men without metastases, not only overall
      mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60
      0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49-0.99).
      CONCLUSIONS: We conclude that socioeconomic disparities in the management and
      mortality in men with high risk prostate cancer exist also within the setting of
      a National Health Care System aiming to provide care on equal terms to all
      residents.

PMID- 21852115
TI  - The comparative kinetic analysis of Acetocell and Lignoboost(r) lignin pyrolysis:
      the estimation of the distributed reactivity models.
AB  - The non-isothermal pyrolysis kinetics of Acetocell (the organosolv) and
      Lignoboost(r) (kraft) lignins, in an inert atmosphere, have been studied by
      thermogravimetric analysis. Using isoconversional analysis, it was concluded that
      the apparent activation energy for all lignins strongly depends on conversion,
      showing that the pyrolysis of lignins is not a single chemical process. It was
      identified that the pyrolysis process of Acetocell and Lignoboost(r) lignin takes
      place over three reaction steps, which was confirmed by appearance of the
      corresponding isokinetic relationships (IKR). It was found that major pyrolysis
      stage of both lignins is characterized by stilbene pyrolysis reactions, which
      were subsequently followed by decomposition reactions of products derived from
      the stilbene pyrolytic process. It was concluded that non-isothermal pyrolysis of
      Acetocell and Lignoboost(r) lignins can be best described by n-th (n>1) reaction
      order kinetics, using the Weibull mixture model (as distributed reactivity model)
      with alternating shape parameters.

PMID- 21852114
TI  - Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and
      pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced
      solid tumours.
AB  - This phase I study (ClinicalTrials.gov ID: NCT00424632) evaluated the safe dose,
      pharmacokinetics, and pharmacodynamics of the aurora kinase A and B inhibitor, PF
      03814735. Patients with advanced solid tumours received oral, once-daily (QD) PF
      03814735 on Schedule A: days 1-5 (5-100mg); or Schedule B: days 1-10 (40-60mg) of
      21-day cycles. Fifty-seven patients were treated: 32 and 25 on Schedules A and B,
      respectively. Dose-limiting toxicities were: febrile neutropenia (Schedule A);
      and increased levels of aspartate amino transferase, left ventricular
      dysfunction, and prolonged low-grade neutropenia (Schedule B). Maximum tolerated
      doses were 80mg QD (Schedule A) and 50mg QD (Schedule B). Common treatment
      related adverse events were mainly mild to moderate and included diarrhoea,
      fatigue, nausea, and vomiting. Nineteen patients achieved stable disease, which
      was prolonged in four cases. PF-03814735 was rapidly absorbed and demonstrated
      linear pharmacokinetics up to 100mg QD; mean terminal half-life ranged from 14.4
      to 23.6h. Aurora B activity, assessed by histone H3 phosphorylation in mitotic
      cells, decreased in tumour tissue from 10/12 patients evaluated (range: -70% to 
      3%). (18)F-fluorodeoxyglucose positron emission tomography demonstrated metabolic
      responses in only 1/21 patients. PF-03814735 was generally well tolerated with
      manageable toxicities, and a recommended phase II dose could be established for
      both schedules. Aurora B activity was inhibited in tumour tissue, but clinical or
      metabolic antitumour activity was limited.

PMID- 21852116
TI  - Structural changes of lignocelluloses by a nonionic surfactant, Tween 20, and
      their effects on cellulase adsorption and saccharification.
AB  - In this work, we found that Tween 20 treatment (0-8 mM) contributed to the cell
      wall collapse of most samples except for those with high lignin contents and high
      crystallinity. Cell wall collapse contributed to the formation of 10- to 50-nm
      pores and not only increased the monolayer saturation amount of adsorbed
      cellulase about 3-3.6 times but also increased the cellulase adsorption rate
      (D(e)/r(2)) about 160-880 times. Moreover, cellulose conversion at 72 h was also
      increased 8.7-21.5% by Tween 20 treatment. On the other hand, the adsorption of
      Tween 20 on Avicel (microcrystalline cellulose) hindered the cellulase reaction
      (adsorption and saccharification). The effect of Tween 20 treatment on the
      crystalline part was insignificant for both lignocelluloses and Avicel. It was
      found that some degree of pretreatment (e.g. lignin removal) that enhances Tween
      20 diffusion into samples is necessary to obtain the structural effects of Tween
      20.

PMID- 21852117
TI  - High level expression of a recombinant xylanase by Pichia pastoris NC38 in a 5 L
      fermenter and its efficiency in biobleaching of bagasse pulp.
AB  - A genetically modified XynA gene from Thermomyces lanuginosus was expressed in
      Pichia pastoris under the control of GAP promoter. P. pastoris expressed greater
      levels of xylanase (160 IU ml(-1)) on BMGY medium without zeocin after 56 h. The
      xylanase production by recombinant P. pastoris was scaled up in a 5L fermenter
      containing 1% glycerol and the highest xylanase production of 139 IU ml(-1) was
      observed after 72 h. Further studies carried out in fermenter under controlled pH
      (5.5) yielded a maximum xylanase production of 177 IU ml(-1) after 72 h. The
      biobleaching efficacy of crude xylanase was also evaluated on bagasse pulp and a
      brightness of 47.4% was observed with 50 IU of crude xylanase used per gram of
      pulp, which was 2.1 points higher in brightness than the untreated samples.
      Reducing sugars (24.8 mg g(-1)) and UV absorbing lignin-derived compounds values
      were considerably higher with xylanase treated samples.

PMID- 21852118
TI  - Modelling real-time simultaneous saccharification and fermentation of
      lignocellulosic biomass and organic acid accumulation using dielectric
      spectroscopy.
AB  - Dielectric spectroscopy (DS) is routinely used in yeast and mammalian
      fermentations to quantitatively monitor viable biomass through the inherent
      capacitance of live cells; however, the use of DS to monitor the enzymatic break
      down of lignocellulosic biomass has not been reported. The aim of the current
      study was to examine the application of DS in monitoring the enzymatic
      saccharification of high sugar perennial ryegrass (HS-PRG) fibre and to relate
      the data to changes in chemical composition. DS was capable of both monitoring
      the on-line decrease in PRG fibre capacitance (C=580 kHz) during enzymatic
      hydrolysis, together with the subsequent increase in conductivity (G=580 kHz)
      resulting from the production of organic acids during microbial growth. Analysis
      of the fibre fractions revealed >50% of HS-PRG lignocellulose had undergone
      enzymatic hydrolysis. These data demonstrated the utility of DS biomass probes
      for on-line monitoring of simultaneous saccharification and fermentation (SSF).

PMID- 21852119
TI  - Production of hydrocarbon compounds by endophytic fungi Gliocladium species grown
      on cellulose.
AB  - Endophytic fungi belonging to the genus Gliocladium are able to degrade plant
      cellulose and synthesize complex hydrocarbons under microaerophilic conditions.
      These fungi could thus be used to produce biofuels from cellulosics without the
      need for hydrolytic pretreatments. Gas chromatography-mass spectrometry-solid
      phase micro-extraction (GC-MS-SPME) of head space gases from Gliocladium cultures
      demonstrated the production of C(6)-C(19) hydrocarbons including hexane, benzene,
      heptane, 3,4-dimethyl hexane, 1-octene, m-xylene, 3-methyl nonane, dodecane,
      tridecane, hexadecane and nonadecane directly from the cellulosic biomass.
      Hydrocarbon production was 100-fold higher in co-cultures of Gliocladium and
      Escherichia coli than in pure Gliocladium cultures. The dry mycelia weight is
      stable at stationary period in co-culture condition which may lead to synthesize
      more hydrocarbons. These fungi could potentially be developed into cost-effective
      biocatalysts for production of biofuels.

PMID- 21852120
TI  - A mesophilic Clostridium species that produces butanol from monosaccharides and
      hydrogen from polysaccharides.
AB  - A unique mesophilic Clostridium species strain BOH3 is obtained in this study,
      which is capable of fermenting monosaccharides to produce butanol and hydrolyzing
      polysaccharides to produce hydrogen (H(2)) and volatile fatty acids (VFAs). From
      30 g/L of glucose and xylose each, batch culture BOH3 was able to produce 4.67
      and 4.63 g/L of butanol. Enhancement treatments by increasing the inoculated
      cells improved butanol production to 7.05 and 7.41 g/L, respectively. Hydrogen
      production (2.47 and 1.93 mmol) was observed when cellulose and xylan (10 g/L
      each) were used, suggesting that strain BOH3 possesses xylanolytic and
      cellulolytic capabilities. These unique features reveal the strain's novelty as
      most wild-type solventogenic strains have not been reported to have such
      properties. Therefore, culture BOH3 is promising in generating butanol and
      hydrogen from renewable feedstock.

PMID- 21852121
TI  - Microbial removal from the separated liquid fraction of anaerobically digested
      pig manure in meso-scale integrated constructed wetlands.
AB  - The aim was to investigate microbial removal from the liquid fraction of
      anaerobically digested pig manure in meso-scale integrated constructed wetlands
      (ICW's) over a 13 month period. Four treatments were investigated: T1 (standard),
      T2 (effluent recycling), T3 (high nutrient loading), and T4 (high flow rate).
      Mean counts of yeasts and moulds and spore-forming bacteria were higher in T3 and
      T4 than in T1 and T2 (P<0.05). Flow through the cells reduced mean counts of
      coliform, yeasts and moulds and spore-forming bacteria across all treatments
      (P<0.01). Counts varied with season; coliform were highest in the Summer
      (P<0.001), with yeasts and moulds highest in the Summer and Autumn (P<0.01) and
      spore-formers lowest in the Autumn (P<0.001). As Salmonella was undetectable in
      the influent and Escherichia coli and Enterococcus were rarely detected it is
      difficult to make conclusions regarding pathogen removal. Further investigations
      using marked strains would allow pathogen tracking within the ICW's.

PMID- 21852122
TI  - Enhancement of rural domestic sewage treatment performance, and assessment of
      microbial community diversity and structure using tower vermifiltration.
AB  - The performance of a novel three-stage vermifiltration (VF) system using the
      earthworm, Eisenia fetida, for rural domestic wastewater treatment was studied
      during a 131-day period. The average removal efficiencies of the tower VF planted
      with Penstemon campanulatus were as follows: chemical oxygen demand, 81.3%;
      ammonium, 98%; total nitrogen, 60.2%; total phosphorus, 98.4%; total nitrogen,
      mainly in the form of nitrate. Soils played an important role in removing the
      organic matter. The three-sectional design with increasing oxygen demand
      concentration in the effluents, and the distribution of certain oxides in the
      padding were likely beneficial for ammonium and phosphorus removal, respectively.
      The microbial community profiles revealed that band patterns varied more or less
      in various matrices of each stage at different sampling times, while the presence
      of earthworms intensified the bacterial diversity in soils. Retrieved sequences
      recovered from the media in VF primarily belonged to unknown bacterium and
      Bacilli of Firmicutes.

PMID- 21852123
TI  - Aqueous ammonia pretreatment of oil palm empty fruit bunches for ethanol
      production.
AB  - Oil palm empty fruit bunches (EFB) were pretreated by aqueous ammonia soaking for
      ethanol production. Pretreated EFB, which were pretreated at the optimal
      conditions of 60  degrees C, 12 h, and 21% (w/w) aqueous ammonia, showed 19.5%
      and 41.4% glucose yields during an enzymatic digestibility test for 96 h when
      using 15 and 60 FPU of cellulase, respectively. Using the pretreated EFB,
      simultaneous saccharification and fermentation for 168 h with 5% (w/v) glucan
      loading and 60 FPU of cellulase and 30 CBU of beta-glucosidase per gram glucan
      resulted in ethanol production of 18.6 g/L titer, 65.6% of theoretical maximum
      yield, and 0.11 g/L/h of productivity.

PMID- 21852124
TI  - Expression and characterization of recombinant Rhizopus oryzae lipase for
      enzymatic biodiesel production.
AB  - The Rhizopus oryzae lipase containing prosequence was expressed in Pichia
      pastoris. Recombinant lipase subunit showed a molecular mass of 32 kDa. The
      maximum activity of recombinant lipase obtained from Mut(s) recombinant was 90
      IU/ml. The enzyme was stable in broad ranges of temperatures and pH, with the
      optimal temperature at 35  degrees C and pH 7.0. The crude recombinant R. oryzae
      lipase can be directly used for the transesterification of plant oils at high
      water content of 60-100% (w/w) based on oil weight. The addition of 80% water to
      the transesterification systems resulted in the yield of methyl ester of 95%, 94%
      and 92% after 72 h using soybean oil, Jatropha curcas seed raw oil and Pistacia
      chinensis seed raw oil as raw material, respectively. These results indicate that
      the recombinant lipase is an effective biocatalyst for enzymatic biodiesel
      production.

PMID- 21852125
TI  - Solid-state anaerobic digestion of spent wheat straw from horse stall.
AB  - The spent wheat straw from horse stall bedding has lower cellulose and
      hemicellulose contents, but higher volatile fatty acid content than raw wheat
      straw. Biogas production from solid-state anaerobic digestion (SS-AD) of spent
      wheat straw and raw wheat straw was compared in this study. The SS-AD tests were
      conducted at 22% total solids (TS) content using inoculum from a liquid AD system
      at three feedstock-to-inoculum (F/I) ratios of 2.0, 4.0, and 6.0. Daily methane
      yields of spent wheat straw peaked 8 and 3 days earlier than those of raw wheat
      straw at F/I ratios of 2.0 and 4.0, respectively. The highest methane yield of
      150.0 L/kg volatile solids (VS) was obtained from spent wheat straw at an F/I
      ratio of 4.0, which was 56.2% higher than that of raw wheat straw. The
      corresponding cellulose and hemicellulose degradation of spent wheat straw was
      24.1% and 49.4% higher than those of raw wheat straw, respectively.

PMID- 21852126
TI  - Kinetic modeling of sporulation and product formation in stationary phase by
      Bacillus coagulans RK-02 vis-a-vis other Bacilli.
AB  - A logistic kinetic model was derived and validated to characterize the dynamics
      of a sporogenous bacterium in stationary phase with respect to sporulation and
      product formation. The kinetic constants as determined using this model are
      particularly important for describing intrinsic properties of a sporogenous
      bacterial culture in stationary phase. Non-linear curve fitting of the
      experimental data into the mathematical model showed very good correlation with
      the predicted values for sporulation and lipase production by Bacillus coagulans
      RK-02 culture in minimal media. Model fitting of literature data of sporulation
      and product (protease and amylase) formation in the stationary phase by some
      other Bacilli and comparison of the results of model fitting with those of
      Bacillus coagulans helped validate the significance and robustness of the
      developed kinetic model.

PMID- 21852127
TI  - Performance of a constructed wetland in treating brackish wastewater from
      commercial recirculating and super-intensive shrimp growout systems.
AB  - A recirculating aquaculture system was developed for treating Pacific white
      shrimp (Litopenaeus vannamei) production wastewater using an integrated vertical
      flow (IVF) and five connected integrated horizontal flow (IHF) constructed
      wetlands as water treatment filters for mesohaline conditions (8.250/00-8.260/00
      salinity). The constructed wetlands demonstrated the ability to reduce total
      nitrogen, total ammonia nitrogen, nitrite nitrogen, nitrate nitrogen, total
      phosphorous, chemical oxygen demand, and total suspended solids to levels
      significantly lower than those in effluents from culture tanks. Various water
      quality parameters in the culture tanks were deemed suitable for shrimp culture.
      The actual ratio of wetland area (A(w)) to culture tank area (A(t)) was 1.1439,
      and the estimated optimal ratio A(w)/A(t) was approximately 1. The IVF-IHF
      wetlands showed flexibility and reliability in consistently removing the main
      pollutants from commercial recirculating and super-intensive shrimp growout
      systems throughout the culture period.

PMID- 21852128
TI  - RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen
      receptor.
AB  - The novel RGD mimetics with phthalimidine central fragment were synthesized with
      the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4
      yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of
      Arg motif. The synthesized compounds potently inhibited platelet aggregation in
      vitro and blocked FITC-Fg binding to alpha(IIb)beta(3) integrin in a suspension
      of washed human platelets. The key alpha(IIb)beta(3) protein-ligand interactions
      were determined in docking experiments.

PMID- 21852129
TI  - Identification of 5,6-substituted 4-aminothieno[2,3-d]pyrimidines as LIMK1
      inhibitors.
AB  - 4-Aminobenzothieno[3,2-d]pyrimidines were previously identified in a high
      throughput screening campaign as LIMK1 inhibitors. Scaffold reversal led to the
      identification of a series of simple 5,6-substituted 4-aminothieno[2,3
      d]pyrimidines with low micromolar inhibition of LIMK1.

PMID- 21852130
TI  - Discovery and characterization of potent and selective 4-oxo-4-(5-(5-phenyl-1,2,4
      oxadiazol-3-yl)indolin-1-yl)butanoic acids as S1P1 agonists.
AB  - S1P(1) receptor driven lymphopenia has proven utility in the treatment of an
      array of autoimmune disease states. As a part of our efforts to develop potent
      and selective S1P(1) receptor agonists, we have identified a novel chemical
      series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid
      S1P(1) receptor agonists.

PMID- 21852131
TI  - Strategies to improve in vivo toxicology outcomes for basic candidate drug
      molecules.
AB  - A valid PLS-DA model to predict attrition in pre-clinical toxicology for basic
      oral candidate drugs was built. A combination of aromatic/aliphatic balance,
      flatness, charge distribution and size descriptors helped predict the successful
      progression of compounds through a wide range of toxicity testing. Eighty percent
      of an independent test set of marketed post-2000 basic drugs could be
      successfully classified using the model, indicating useful forward predictivity.
      The themes within this work provide additional guidance for medicinal design
      chemists and complement other literature property guidelines.

PMID- 21852132
TI  - 4-Thiophenoxy-2-trichloromethyquinazolines display in vitro selective
      antiplasmodial activity against the human malaria parasite Plasmodium falciparum.
AB  - A series of original quinazolines bearing a 4-thiophenoxy and a 2-trichloromethyl
      group was synthesized in a convenient and efficient way and was evaluated toward
      its in vitro antiplasmodial potential. The series revealed global good activity
      against the K1-multi-resistant Plasmodium falciparum strain, especially with hit
      compound 5 (IC(50)=0.9 MUM), in comparison with chloroquine and doxycycline
      chosen as reference-drugs. Both the in vitro cytotoxicity study which was
      conducted on the human HepG2 cell line and the in vitro antitoxoplasmic screening
      against Toxoplasma gondii indicate that this series presents an interesting
      selective antiplasmodial profile. Structure-activity- and toxicity relationships
      highlight that the trichloromethyl group plays a key role in the antiplasmodial
      activity and also show that the modulation of the thiophenol moiety influences
      the toxicity/activity ratio.

PMID- 21852133
TI  - Phenylethynylbenzenesulfonamide regioisomers strongly and selectively inhibit the
      transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the
      cytosolic isoforms I and II.
AB  - A series of compounds incorporating regioisomeric phenylethynylbenzenesulfonamide
      moieties has been investigated for the inhibition of four human carbonic
      anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between
      the low nanomolar to the milliomolar range has been observed against them, with
      several low nanomolar and tumor-CA selective inhibitors detected. The position of
      the sulfamoyl group with respect to the alkyne functionality, and the nature of
      the moieties substituting the second aromatic ring were the principal structural
      features influencing CA inhibition. The para-sulfamoyl-substituted derivatives
      were effective inhibitors of CA IX and XII, the meta-substituted regioisomers of
      CA I, IX and XII, whereas the ortho-substituted sulfonamides were weak inhibitors
      of CA I, II and IX, but inhibited significantly CA XII.

PMID- 21852134
TI  - 2010 Marigold therapeutic strategies for myotonic dystrophy.

PMID- 21852135
TI  - Objective assessment of aesthetic outcome after breast conserving therapy:
      subjective third party panel rating and objective BCCT.core software evaluation.
AB  - We analysed intra- and inter-rater agreement of subjective third party assessment
      and agreement with a semi-automated objective software evaluation tool
      (BCCT.core). We presented standardized photographs of 50 patients, taken shortly
      and one year after surgery to a panel of five breast surgeons, six breast nurses,
      seven members of a breast cancer support group, five medical and seven non
      medical students. In two turns they rated aesthetic outcome on a four point
      scale. Moreover the same photographs were evaluated by the BCCT.core software.
      Intra-rater agreement in the panel members was moderate to substantial (k = 0.4
      0.5; wk = 0.6-0.7; according to different subgroups and times of assessment). In
      contrast inter-rater agreement was only slight to fair (mk = 0.1-0.3). Agreement
      between the panel participants and the software was fair (wk = 0.24-0.45).
      Subjective third party assessment only fairly agree with objective BCCT.core
      evaluation just as third party participants do not agree well among each other.

PMID- 21852136
TI  - Late lines of treatment benefit survival in metastatic breast cancer in current
      practice?
AB  - Metastatic breast cancer is mostly incurable. Progressively overall survival (OS)
      has improved but few authors have studied treatment globally versus for each line
      and demonstrated the interest of chemotherapy (CT) after the third line. We
      selected recent patients treated during the "taxane/anti-aromatase era" for each
      line given. 529 received CT and 383 hormonotherapy. OS was assessed; from the
      date of first metastasis and from Day 1 of each CT line. Median OS was 34.1
      months; 226 patients received >3 lines of CT with a steady median OS for late
      lines, 11.4 months per line (range 10.4-12.6). Clinical benefit after the third
      line of CT was obtained for 29.2-36.6% of patients. CT lasted 11.7 months
      "on"versus 20.6 months "off" CT. These results may support the use of more than 3
      CT lines; each line can contribute to a longer survival.

PMID- 21852137
TI  - Phytochrome signaling mechanisms and the control of plant development.
AB  - As they emerge from the ground, seedlings adopt a photosynthetic lifestyle, which
      is accompanied by dramatic changes in morphology and global alterations in gene
      expression that optimizes the plant body plan for light capture. Phytochromes are
      red and far-red photoreceptors that play a major role during photomorphogenesis,
      a complex developmental program that seedlings initiate when they first encounter
      light. The earliest phytochrome signaling events after excitation by red light
      include their rapid translocation from the cytoplasm to subnuclear bodies
      (photobodies) that contain other proteins involved in photomorphogenesis,
      including a number of transcription factors and E3 ligases. In the light,
      phytochromes and negatively acting transcriptional regulators that interact
      directly with phytochromes are destabilized, whereas positively acting
      transcriptional regulators are stabilized. Here, we discuss recent advances in
      our knowledge of the mechanisms linking phytochrome photoactivation in the
      cytoplasm and transcriptional regulation in the nucleus.

PMID- 21852140
TI  - Anthraquinone derivatives induce G2/M cell cycle arrest and apoptosis in NTUB1
      cells.
AB  - Thirteen anthraquinone derivatives 5-17 including two 3-(3-alkylaminopropoxy)
      9,10-anthraquinone (NHA) derivatives 5 and 6, and 11 1-hydroxy-3-(3
      alkylaminopropoxy)-9,10-anthraquinone (MHA) derivatives 7-17 were synthesized,
      evaluated for cytotoxicities against two cancer cell lines, and assayed the
      generation of reactive oxygen species (ROS) in NTUB1 cells (a human bladder
      carcinoma cell line). Compound 9 bearing a pyrrolidinyl group induced the
      stronger cytotoxic effect than those of other synthesized NHA and MHA
      derivatives. Exposure of NTUB1 cells to 9, 13, and 17 for 24h significantly
      increased the production of ROS, respectively. Flow cytometric analysis exhibited
      that the exposure of NTUB1 cells to the selective 9 led to the G2/M phase arrest
      accompanied by an increase of apoptotic cell death after the incubation for 24h.
      Compound 9 induced up-regulation of cyclinB1 and p21 expressions. Biological
      results suggested that the induction of G2/M arrest, apoptosis, and cell death by
      9 may associate with increased expression of p21 and cyclin B1, elevation of Bax
      and p53 levels, and generation of ROS in the cell. In conclusion, these series of
      compounds may be used as anticancer agents.

PMID- 21852139
TI  - A comparative anatomical study of the human knee and six animal species.
AB  - PURPOSE: Animal models are an indispensable tool for developing and testing new
      clinical applications regarding the treatment of acute injuries and chronic
      diseases of the knee joint. Therefore, the purpose of this study was to compare
      the anatomy of the intra-articular structures of the human knee to species
      commonly used in large animal research studies. METHODS: Fresh frozen cow (n=4),
      sheep (n=3), goat (n=4), dog (n=4), pig (n=5), rabbit (n=5), and human (n=4)
      cadaveric knees were used. Passive range of motion and intra-articular structure
      sizes of the knees were measured, the structure sizes normalized to the tibial
      plateau, and compared among the species. RESULTS: Statistically significant
      differences in the range of motion and intra-articular structure sizes were found
      among all the species. Only the human knee was able to attain full extension.
      After normalization, only the pig ACL was significantly longer than the human
      counterpart. The tibial insertion site of the ACL was split by the anterior
      lateral meniscus attachment in the cow, sheep, and pig knees. The sheep PCL had
      two distinct tibial insertion sites, while all the other knees had only one.
      Furthermore, only in human knees, both lateral meniscal attachments were located
      more centrally than the medial meniscal attachments. CONCLUSIONS/CLINICAL
      RELEVANCE: Despite the relatively preserved dimensions of the cruciate ligaments,
      menisci, and intercondylar notch amongst human and animals, structural
      differences in the cruciate ligament attachment sites and morphology of the
      menisci between humans and animals are important to consider when selecting an
      animal model.

PMID- 21852141
TI  - Residual microstructure associated with impact crater in Ti-6Al-4V meshes
      reinforced 5A06Al alloy matrix composite.
AB  - In this paper, TC4(m)/5A06Al composite was hypervelocity impacted by 2024
      aluminium projectile with the diameter of 2mm and with the impact velocity of 3.5
      km/s. The residual microstructure was observed by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM) and high-resolution transmission
      electron microscopy (HREM). The TC4-Al interface before impact was composed of
      TiAl(3) phase and Ti(3)Al phase. Near the pithead, separation of TC4 fibers and
      Al matrix occurred along the impact direction. Around the middle of the crater,
      TC4 fibers were sheared into several sections. Near the bottom of crater,
      adiabatic shear band (ASB) occurred in TC4 fiber, while the angle between shear
      plane and cross section was 45 degrees . The crack propagated along TC4-Ti(3)Al
      interface during impact and some Ti(3)Al phase at the TC4-Al interface
      transformed to amorphous with few nanocrystals after hypervelocity impact.

PMID- 21852138
TI  - Prolyl isomerase Pin1 as a molecular switch to determine the fate of
      phosphoproteins.
AB  - Pin1 is a highly conserved enzyme that only isomerizes specific phosphorylated
      Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes.
      Such conformational changes represent a novel and tightly controlled signaling
      mechanism regulating a spectrum of protein activities in physiology and disease;
      often through phosphorylation-dependent, ubiquitin-mediated proteasomal
      degradation. In this review, we summarize recent advances in elucidating the role
      and regulation of Pin1 in controlling protein stability. We also propose a
      mechanism by which Pin1 functions as a molecular switch to control the fates of
      phosphoproteins. We finally stress the need to develop tools to visualize
      directly Pin1-catalyzed protein conformational changes as a way to determine
      their roles in the development and treatment of human diseases.

PMID- 21852142
TI  - Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the Tracerlab FXFN
      and Tracerlab MXFDG module for imaging the peripheral benzodiazepine receptor
      with PET.
AB  - [(18)F]PBR111 and [(18)F]PBR102 are selective radioligands for imaging of the
      Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated
      method for the radiosynthesis of [(18)F]PBR111 and [(18)F]PBR102 in the Tracerlab
      FX(FN) (30+/-2% radiochemical yield non-decay-corrected for both tracers) and
      Tracerlab MX(FDG) (25+/-2% radiochemical yield non-decay-corrected for both
      tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers,
      radiochemical purity was >99% and specific activity was >150GBq/MUmol after less
      than 60min of preparation time.

PMID- 21852143
TI  - Application of the Monte Carlo method for the efficiency calibration of CsI and
      NaI detectors for gamma-ray measurements from terrestrial samples.
AB  - Gamma-ray measurements in terrestrial/environmental samples require the use of
      high efficient detectors because of the low level of the radionuclide activity
      concentrations in the samples; thus scintillators are suitable for this purpose.
      Two scintillation detectors were studied in this work; CsI(Tl) and NaI(Tl) with
      identical size for measurement of terrestrial samples for performance study. This
      work describes a Monte Carlo method for making the full-energy efficiency
      calibration curves for both detectors using gamma-ray energies associated with
      the decay of naturally occurring radionuclides (137)Cs (661keV), (40)K (1460keV),
      (238)U ((214)Bi, 1764keV) and (232)Th ((208)Tl, 2614keV), which are found in
      terrestrial samples. The magnitude of the coincidence summing effect occurring
      for the 2614keV emission of (208)Tl is assessed by simulation. The method
      provides an efficient tool to make the full-energy efficiency calibration curve
      for scintillation detectors for any samples geometry and volume in order to
      determine accurate activity concentrations in terrestrial samples.

PMID- 21852144
TI  - Survival of Cd-exposed Arabidopsis thaliana: are these plants reproductively
      challenged?
AB  - Plants exposed to cadmium (Cd) show morphological and physiological disorders. To
      increase our knowledge regarding Cd-induced signalling, most often the effects of
      acute exposure are investigated. However, this does not allow in-depth analysis
      of morphological effects. Therefore, we chronically exposed Arabidopsis thaliana
      plants to environmentally realistic Cd concentrations (5 or 10 MUM) and, using a
      described phenotypic framework methodology, we determined the impact of Cd on the
      plant's ability to complete its life cycle and produce germinative seeds. Visible
      Cd-induced morphological changes were observed within a short exposure period,
      with chlorotic and anthocyanous leaf colouring occurring dose-dependently.
      Although rosette growth was severely reduced in Cd-exposed plants, all plants
      were able to emerge inflorescences and produce siliques containing germinative
      seeds, thus confirming the non-lethality of the used Cd concentrations. Although
      the growth inhibition of Cd-exposed plants was dependent on the dose, both
      concentrations had similar effects on inflorescence height and silique counts. In
      conclusion, vegetative growth of plants chronically exposed to Cd is inhibited in
      a concentration-dependent manner. However, the effect on plant regeneration is
      clearly stress-determined but independent on the Cd concentration applied. In
      Arabidopsis thaliana, vegetative and reproductive growth are differentially
      influenced by Cd.

PMID- 21852145
TI  - The wind of change.

PMID- 21852146
TI  - Double orifice mitral valve causing severe regurgitation.

PMID- 21852147
TI  - Low-power light and isolated rat hearts after ischemia of myocardium.
AB  - We studied the influence of low-intensity red light on restoration of isolated
      heart contractility, on lipid peroxidation processes and a state of the
      superoxide dismutase (SOD) activity in myocardial tissues of isolated hearts. It
      was found that after ischemia modeled and perfusion restored the light
      illumination results in acceleration of myocardial contractility recovery, rising
      of the SOD activity and reduction in the amount of molecular products of lipid
      peroxidation.

PMID- 21852148
TI  - Pleiotropic effects of growth hormone signaling in aging.
AB  - Growth hormone (GH) affects somatic growth, sexual maturation, body composition
      and metabolism, as well as aging and longevity. Mice lacking GH or GH receptor
      outlive their normal siblings and exhibit symptoms of delayed aging associated
      with improved insulin signaling and increased stress resistance. Beneficial
      effects of eliminating the actions of GH are counterintuitive but conform to the
      concept of antagonistic pleiotropy. Evolutionary selection for traits promoting
      early-life fitness and reproductive success could account for post-reproductive
      deficits. Reciprocal relationships between GH signaling and longevity discovered
      in mutant mice apply also to normal mice, other mammalian species, and perhaps
      humans. This review summarizes the present understanding of the multifaceted
      relationship between somatotropic signaling and mammalian aging.

PMID- 21852150
TI  - Organ transplantation and autoimmunity: common mechanisms common therapies.

PMID- 21852149
TI  - Epicardial adipose tissue: emerging physiological, pathophysiological and
      clinical features.
AB  - Epicardial adipose tissue is an unusual visceral fat depot with anatomical and
      functional contiguity to the myocardium and coronary arteries. Under
      physiological conditions, epicardial adipose tissue displays biochemical,
      mechanical and thermogenic cardioprotective properties. Under pathological
      circumstances, epicardial fat can locally affect the heart and coronary arteries
      through vasocrine or paracrine secretion of proinflammatory cytokines. What
      influences this equilibrium remains unclear. Improved local vascularization,
      weight loss, and targeted pharmaceutical interventions could help to return
      epicardial fat to its physiological role. This review focuses on the emerging
      physiological and pathophysiological aspects of the epicardial fat and its
      numerous and innovative clinical applications. Particular emphasis is placed on
      the paracrine/endocrine properties of epicardial fat and its role in the
      development and progression of atherosclerosis.

PMID- 21852152
TI  - Spinal stiffness in asymptomatic subjects.
AB  - The objective of the study was to measure postero-anterior stiffness of
      thoracolumbar spine from normal asymptomatic subjects at T(4), T(9), and L(2)
      levels using a standardized device and protocol. Sixteen volunteer subjects
      (eight males and eight females) meeting the inclusion and exclusion criteria were
      recruited for the study. Their T(4), T(9), and L(2) spinous processes were
      identified and marked. These spinous processes were cyclically loaded with 22.5
      N, 45 N, 90 N, and 135 N fixed forces at 0.1 Hz in postero-anterior direction by
      a computer controlled and operated Therapeutic Spinal Mobilizer (TSM) for five
      cycles to the level of subject's acceptance of the load magnitude. The magnitude
      of the force and displacement experienced at the spinal level were recorded using
      a load cell and linear variable differential transducer. The stiffness was
      obtained from the slope of the load/deformation curve. The stiffness values were
      subjected to analysis of variance to determine the effect of independent
      variables. The stiffness at different levels was significantly different
      (p<0.0001) and it was significantly affected by the testing load (p<0.0001). The
      age, sex, height and weight were not significantly associated with the stiffness,
      neither were the cycles at the same load. The postero-anterior stiffness of the
      thoracolumbar spine is different at different spinal levels and varies with
      testing loads.

PMID- 21852151
TI  - Immune intervention in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease that results in the
      specific immune destruction of insulin producing beta cells. Currently there is
      no cure for T1D and treatment for the disease consists of lifelong administration
      of insulin. Immunotherapies aimed at preventing beta cell destruction in T1D
      patients with residual c-peptide or in individuals developing T1D are being
      evaluated. Networks of researchers such as TrialNet and the Immune Tolerance
      Network in the U.S. and similar networks in Europe have been established to
      evaluate such immunotherapies. This review focuses on immune intervention for the
      prevention and amelioration of human T1D with a focus on potential immune
      suppressive, antigen specific and environmental therapies.

PMID- 21852153
TI  - Circulating endothelial cells and stroke: influence of stroke subtypes and
      changes during the course of disease.
AB  - BACKGROUND: Circulating endothelial cells (CECs) are a novel and valuable marker
      of endothelial damage in a variety of vascular disorders. There is limited
      information as to CEC counts and the time course of CECs in subtypes of stroke.
      METHODS: We studied 49 patients with stroke (18 with atherothrombotic infarction
      in the territory of the middle cerebral artery, 16 with cardioembolic stroke, and
      15 with lacunar stroke). We also included 16 healthy controls and 64 disease
      controls. CECs were isolated and enumerated with lectin-augmented CD146-driven
      immunomagnetic isolation. Neurologic deficit was assessed with the European
      Stroke Scale (ESS) and the National Institutes of Health Stroke Scale (NIHSS).
      Recovery was assessed with the modified Rankin scale (mRS). RESULTS: Healthy
      controls had low numbers of CECs (median, 8 cells/mL; mean, 9 cells/mL; range, 0
      16 cells/mL; n = 16). Patients with stroke had markedly elevated numbers of CECs
      at presentation. Patients with atherothrombotic infarction had 32 cells per
      milliliter (mean, 42 cells/mL; range, 24-116 cells/mL; n = 18; P < .001 when
      compared to controls). Patients with lacunar stroke had 68 cells per milliliter
      (mean, 68 cells/mL; range, 8-144 cells/mL; n = 15; P < .001 when compared to
      controls). Patients with cardioembolic stroke had 46 cells per milliter (mean, 54
      cells/mL; range, 24-116 cells/mL; n = 16; P < .001 when compared to healthy
      controls). There was a tendency towards higher numbers of CECs in lacunar stroke.
      The number of CECs peaked at day 7 in patients with atherothrombotic infarction
      and came back to normal at day 90. In contrast, CECs in patients with acute
      lacunar stroke and cardioembolic stroke decreased progressively until day 90.
      CONCLUSIONS: CECs are markers of endothelial damage and/or repair in stroke.
      Differences during the course of disease are likely to reflect different
      pathophysiology.

PMID- 21852154
TI  - Diversity of stroke presentation in CADASIL: study from patients harboring the
      predominant NOTCH3 mutation R544C.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a single-gene disorder of the cerebral small
      blood vessels caused by mutations in the NOTCH3 gene. Several characteristic
      population-specific clinical phenotypes and neuroimaging features have been
      reported in CADASIL. This study investigated the clinical stroke presentation and
      cranial magnetic resonance imaging (MRI) findings in a group of patients with
      CADASIL. We reviewed the clinical stroke presentation and brain MRI findings in
      73 consecutive Korean patients aged >18 years diagnosed with CADASIL between May
      2004 and April 2009. Brain MRI images were also scored for lacunar infarction and
      cerebral microbleeds. Intracranial atherosclerosis (ICAS) was assessed by
      magnetic resonance angiography. Disability was measured with the modified Rankin
      scale (mRS) and classified as good (mRS score 0-2) or poor (mRS score 3-5). In
      this study, 65 of the 73 patients (90.3%) had the same R544C genotype. A total of
      40 episodes of cerebral infarction were confirmed in 31 patients, with a mean age
      at onset of 58.8 +/- 11.4 years (range, 38-76 years). Twelve patients (16.9%) had
      ICAS, and 5 of these patients had symptomatic stenoses. Intracerebral hemorrhage
      occurred in 9 patients (12.3%). Both intracerebral hemorrhage and ICAS were
      associated with poor clinical outcome. Our data demonstrate the diversity of
      clinical stroke presentation according to ethnicity and vascular risk factors.

PMID- 21852155
TI  - Gastroesophageal reflux during enteral feeding in stroke patients: a 24-hour
      esophageal pH-monitoring study.
AB  - BACKGROUND: Patients who are unable to eat or drink after stroke may receive
      percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Although
      the most common serious complication is well known to be aspiration pneumonia,
      the role of gastroesophageal reflux (GER) has not been fully assessed. The aim of
      this study was to examine, by means of 24-hour esophageal pH monitoring, whether
      GER is related to aspiration pneumonia and whether the size and laterality of
      brain lesions influence GER. METHODS: Sixteen stroke patients were examined using
      a Degitrapper pH400 (Medtronic Japan Co., Tokyo, Japan) and Zinetics 24ME
      multiuse pH catheter (Medtronic). All patients had stroke lesions in the
      territory of the left or right middle cerebral artery that were confirmed by
      magnetic resonance imaging (MRI) and were receiving PEG or nasogastric feeding.
      Stroke volume was measured with MRIcron software. RESULTS: Nine patients (56%)
      were diagnosed with GER, and 10 (63%) developed aspiration pneumonia after
      enteral feeding. The rate of aspiration pneumonia was significantly higher in
      patients with GER (88.9%) than in those without GER (42.9%; P = .04). Patients
      with left hemispheric lesions had a significantly higher incidence of acid reflex
      than those with right lesions (116 +/- 105 vs 13 +/- 17; P = .04). There were no
      significant differences in total time of acid reflux or mean pH value between
      patients with left and right hemispheric lesions. The lesion volume had no
      significant effect on any of 3 indices of GER. CONCLUSIONS: GER is associated
      with aspiration pneumonia and occurs more often in patients with stroke lesions
      in the left hemisphere.

PMID- 21852156
TI  - Thrombolysis for acute ischemic stroke in Joint Commission-certified and 
      noncertified hospitals in Michigan.
AB  - BACKGROUND: The Joint Commission (JC) for Accreditation of Healthcare
      Organizations has devised disease specific certification programs for hospitals,
      including stroke. JC certification as a primary stroke center (PSC) suggests that
      the hospital has critical measures in place to ensure improving stroke outcomes
      over the long term. In this study, we focused on the delivery of care for
      patients with acute ischemic and compared differences in JC-certified and 
      noncertified centers in Michigan. METHODS: We performed a systematic chart review
      of patients with acute ischemic stroke from 10 Michigan hospitals, half of whom
      were JC-certified PSCs. Sixty charts were randomly chosen from 1 calendar year
      from each hospital. An experienced nurse performed the data abstraction, and data
      analysis was performed with the Fisher exact test. RESULTS: A total of 602 charts
      -of which 302 were from JC-certified PSCs--were chosen for the study. The 2
      groups were similar with regard to stroke risk factors except that there were
      significantly more patients with atrial fibrillation in noncertified centers and
      there were more African American patients in JC-certified PSCs. Significantly
      more patients were considered for thrombolytic therapy in JC-certified PSCs
      compared to noncertified centers (90.4% v 66%; P = .0001). Overall, 3.8% of
      patients had received thrombolytic therapy without any significant difference
      between JC-certified PSCs and noncertified centers (4.6% v 3%; adjusted odds
      ratio 1.64; 95% confidence interval 0.64-4.19; P = .87). However, thrombolysis
      rates among eligible patients was significantly higher in the JC-certified PSCs
      (48.2% v 8.8%; P = .0001). The most common reason documented for not giving
      thrombolytic therapy was late arrival outside the therapeutic window, which was
      more common in JC-certified PSCs (72.8% v 55.6%; P = .0001) compared to
      noncertified centers. Seventy-four percent of patients from JC-certified PSCs
      were discharged home or to inpatient rehabilitation facility compared to 71% (P =
      .38) from noncertified hospitals. The mean length of stay was marginally shorter
      in JC-certified PSCs compared to noncertified centers (5.53 v 6.25 days; P =
      .08). CONCLUSIONS: Rates of thrombolysis administration for acute stroke patients
      across Michigan were low in both JC-certified and noncertified hospitals,
      although better processes were in place in JC-certified PSCs. While there was no
      overall difference in the administration of thrombolytic treatment, a greater
      number of the eligible patients received thrombolysis in the certified centers.
      There was a tendency to shorter lengths of stay at JC-certified PSCs, but there
      was no significant difference in discharge to home, inpatient rehabilitation, or
      inpatient mortality in this study.

PMID- 21852157
TI  - The unpredictable past: spontaneous autobiographical memories outnumber
      autobiographical memories retrieved strategically.
AB  - Involuntary autobiographical memories are spontaneously arising memories of
      personal events, whereas voluntary memories are retrieved strategically.
      Voluntary remembering has been studied in numerous experiments while involuntary
      remembering has been largely ignored. It is generally assumed that voluntary
      recall is the standard way of remembering, whereas involuntary recall is the
      exception. However, little is known about the actual frequency of these two types
      of remembering in daily life. Here, 48 Danish undergraduates recorded their
      involuntary versus voluntary autobiographical memories during a day using a
      mechanical counter. Involuntary memories were reported three times as frequently
      as voluntary memories. Compared to voluntary memories, they were associated less
      with problem solving and social sharing and more with day dreaming, periods of
      boredom, no reasons for remembering and predominantly came to mind during
      unfocused attention. The findings suggest that involuntary recall is a typical
      way of accessing the personal past.

PMID- 21852158
TI  - Age is a risk factor for maladaptive changes of the pulmonary root in rats
      exposed to increased pressure loading.
AB  - INTRODUCTION: Pulmonary artery root does not adapt properly when exposed to
      increased pressure stress, with progressive dilatation. The aim of this study was
      to evaluate, in an animal model, the histologic changes of the pulmonary root
      wall under increased pressure load. METHODS AND RESULTS: To increase the systolic
      pressure in the pulmonary root, a banding of the pulmonary artery (PAB) was
      performed in 10 adult Sprague-Dawley rats and in 10 weanlings, using 7 adults and
      8 weanlings as controls. We analyzed the structural changes of the pulmonary
      artery root after 30 days of increased pressure load. The mean pressure gradient
      across the banded pulmonary trunk was 53.57 +/- 10 mmHg in the adult rats and
      86.73 +/- 15 mmHg in the weanlings. The pulmonary artery wall was significantly
      thicker in both age groups of PAB rats when compared to age-matched controls,
      showing also architectural structural changes, as a higher degree of mucoid
      degeneration, medionecrosis, and fibrosis as well as elastic fibers
      fragmentation. The apoptotic index was also increased in both PAB age groups. We
      also confirmed the physiologic higher degree of elastic fibers disarray in adult
      rats when compared to weanlings. CONCLUSIONS: The pulmonary artery wall seems to
      present maladaptive architectural changes in the media when exposed to systemic
      pressure. The PAB-related increase of the apoptotic index seems to reflect an
      accelerated involution of the pulmonary root's media. The physiologic higher
      degree of elastic fibers disarray in adult rats can possibly influence the worst
      adaptation of the pulmonary arterial wall to a systemic pressure load.

PMID- 21852159
TI  - Verification bias: an under-recognized source of error in assessing the efficacy
      of MRI of the meniscii.
AB  - RATIONALE AND OBJECTIVES: The sensitivity and specificity of magnetic resonance
      imaging (MRI) for diagnosis of meniscal tears has been studied extensively, with
      tears usually verified by surgery. However, surgically unverified cases are often
      not considered in these studies, leading to verification bias, which can falsely
      increase the sensitivity and decrease the specificity estimates. Our study
      suggests that such bias may be very common in the meniscal MRI literature, and
      illustrates techniques to detect and correct for such bias. MATERIALS AND
      METHODS: PubMed was searched for articles estimating sensitivity and specificity
      of MRI for meniscal tears. These were assessed for verification bias, deemed
      potentially present if a study included any patients whose MRI findings were not
      surgically verified. Retrospective global sensitivity analysis (GSA) was
      performed when possible. RESULTS: Thirty-nine of the 314 studies retrieved from
      PubMed specifically dealt with meniscal tears. All 39 included unverified
      patients, and hence, potential verification bias. Only seven articles included
      sufficient information to perform GSA. Of these, one showed definite verification
      bias, two showed no bias, and four others showed bias within certain ranges of
      disease prevalence. Only 9 of 39 acknowledged the possibility of verification
      bias. CONCLUSION: Verification bias is underrecognized and potentially common in
      published estimates of the sensitivity and specificity of MRI for the diagnosis
      of meniscal tears. When possible, it should be avoided by proper study design. If
      unavoidable, it should be acknowledged. Investigators should tabulate unverified
      as well as verified data. Finally, verification bias should be estimated; if
      present, corrected estimates of sensitivity and specificity should be used. Our
      online web-based calculator makes this process relatively easy.

PMID- 21852160
TI  - Robust, standardized quantification of pulmonary emphysema in low dose CT exams.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to present and evaluate a
      fully automated system for emphysema quantification on low-dose computed
      tomographic images. The platform standardizes emphysema measurements against
      changes in the reconstruction algorithm and slice thickness. MATERIALS AND
      METHODS: Emphysema was quantified in 149 patients using a fully automatic, in
      house developed software (the Robust Automatic On-Line Pulmonary Helper). The
      accuracy of the system was evaluated against commercial software, and its
      reproducibility was assessed using pairs of volume-corrected images taken 1 year
      apart. Furthermore, to standardize quantifications, the effect of changing the
      reconstruction parameters was modeled using a nonlinear fit, and the inverse of
      the model function was then applied to the data. The association between
      quantifications and pulmonary function testing was also evaluated. The accuracy
      of the in-house software compared to that of commercial software was measured
      using Spearman's rank correlation coefficient, the mean difference, and the
      intrasubject variability. Agreement between the methods was studied using Bland
      Altman plots. To assess the reproducibility of the method, intraclass correlation
      coefficients and Bland-Altman plots were used. The statistical significance of
      the differences between the standardized data and the reference data (soft-tissue
      reconstruction algorithm B40f; slice thickness, 1 mm) was assessed using a paired
      two-sample t test. RESULTS: The accuracy of the method, measured as intrasubject
      variability, was 3.86 mL for pulmonary volume, 0.01% for emphysema index, and
      0.39 Hounsfield units for mean lung density. Reproducibility, assessed using the
      intraclass correlation coefficient, was >0.95 for all measurements. The
      standardization method applied to compensate for variations in the reconstruction
      algorithm and slice thickness increased the intraclass correlation coefficients
      from 0.87 to 0.97 and from 0.99 to 1.00, respectively. The correlation of the
      standardized measurements with pulmonary function testing parameters was similar
      to that of the reference (for the emphysema index and the obstructive subgroup:
      forced expiratory volume in 1 second, -0.647% vs -0.615%; forced expiratory
      volume in 1 second/forced vital capacity, -0.672% vs -0.654%; and diffusing
      capacity for carbon monoxide adjusted for hemoglobin concentration, -0.438% vs 
      0.523%). CONCLUSIONS: The new emphysema quantification method presented in this
      report is accurate and reproducible and, thanks to its standardization method,
      robust to changes in the reconstruction parameters.

PMID- 21852161
TI  - Comment on 'Surveillance after EVAR based on duplex ultrasound and abdominal
      radiography' Contrast Enhanced Aortic Duplex Ultrasonography Scanning (CEADUSS)
      for post-EVAR surveillance.

PMID- 21852162
TI  - Vascular access for haemodialysis in patients with central vein thrombosis.
AB  - OBJECTIVES: Dialysis-dependent patients often have central venous drainage
      complications. In patients with functioning arm arteriovenous fistula, this may
      result in venous hypertension, arm oedema and vascular access failure.
      Percutaneous angioplasty and stent implantation might be inadequate to resolve
      these issues. In these cases, new access can potentially be created with
      anastomosis to the subclavian vein, iliac vein or vena cava or by making a veno
      venous graft to bypass the thrombosis. The aim of this study was to assess the
      utility of unusual bypasses in vascular access in patients with the central vein
      thrombosis. MATERIALS: A total of 49 patients were treated. The mean number of
      previous vascular access surgery procedures was 7.6 (3-17). We performed 19
      axillo-iliac, 14 axillo-axillary bypasses and 16 conduits from the arm fistula to
      the jugular (nine conduits) or subclavian (seven conduits) vein for haemodialysis
      purposes. RESULTS: All fistulas except one were used for haemodialysis. One
      patient died before the first use of the fistula. At 12 months, the primary,
      primary assisted and secondary patency rates were 85.4%, 89.6% and 95.8%,
      respectively. The follow-up period ranged from 1 to 84 months. CONCLUSION:
      Unusual grafts are an efficient option as a permanent vascular access for
      haemodialysis purposes in patients with central vein occlusion.

PMID- 21852163
TI  - Cilostazol stimulates revascularisation in response to ischaemia via an eNOS
      dependent mechanism.
AB  - OBJECTIVES: Cilostazol is known to be a selective inhibitor of phosphodiesterase
      3 and is generally used to treat intermittent claudication caused by peripheral
      arterial disease. However, there is little information concerning the effect of
      cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates
      the angiogenic process in vivo employing a hindlimb model of ischaemia-induced
      angiogenesis. DESIGN: This was an experimental study. MATERIALS AND METHODS: Wild
      type (WT) mice were randomly divided into two groups and were treated with or
      without cilostazol. One week later, the mice were subjected to unilateral
      hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and
      capillary density stained with CD31. The expression of endothelial nitric oxide
      synthase (eNOS) was assessed by immunoblotting. RESULTS: WT mice treated with
      cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic
      surgery on post-operative day 14 based upon laser Doppler measurements of blood
      flow (cilostazol-treated group, 0.54 +/- 0.13 vs. control group, 0.38 +/- 0.11; P
      <-0.05). The capillary density in the ischaemic hindlimb was also significantly
      greater in WT mice treated with cilostazol than in non-treated WT mice
      (cilostazol-treated group, 1.63 +/- 0.10 vs. control group, 1.15 +/- 0.12; P-<
      0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation
      of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l
      arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb
      perfusion. CONCLUSIONS: Our observations indicate that cilostazol can promote neo
      vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism.
      Cilostazol could be useful for treatment of ischaemic limb diseases.

PMID- 21852164
TI  - Insulin-like growth factor I - a novel biomarker of abdominal aortic aneurysms.
AB  - OBJECTIVE: The study aimed to test the potential role of insulin-like growth
      factor I (IGF-I) and IGF-II as biomarkers for abdominal aortic aneurysm (AAA).
      METHODS AND RESULTS: IGF-I and II levels were analysed in 115 patients with
      screening diagnosed AAA kept under annual surveillance for 10 years. Serum IGF-I
      correlated positively with AAA size and growth rate (r = 0.23, P = 0.016 and r =
      0.27, P = 0.004), persisting after adjustment for potential confounders. Serum
      IGF-I level predicted cases needing later surgery (AOC: 0.63; 95% confidence
      interval: 0.52-0.73). CONCLUSIONS: In this prospective, long-term study, baseline
      serum IGF-I correlated positively with AAA size and growth rate and predicted
      future need for preventive surgery.

PMID- 21852165
TI  - Agreement between computed tomography and ultrasound on abdominal aortic
      aneurysms and implications on clinical decisions.
AB  - OBJECTIVES: The United Kingdom abdominal aortic aneurysm (AAA) screening
      programme refers aneurysms with ultrasound (US) diameters of >=5.5 cm to vascular
      services for consideration of computed tomography (CT) and intervention. We
      investigated the discrepancy between US and CT, implications on clinical
      decisions and question at which stage CT be used. DESIGN/METHODS: AAA USs over 5
      years were retrospectively analysed. Patients included had aneurysms measuring
      >=5 cm on US with subsequent CT within 2 months (n = 123). Based on maximum US
      diameters, 44 patients had aneurysms between 5 and 5.4 cm (group I) and 79
      patients >=5.5 cm (group II). Results were cross-referenced. Correlation and
      limits of agreement were calculated. Two radiologists re-measured 44 pairs of
      CT/US scans and the inter-observer bias in determining discrepancies between
      imaging modalities calculated. RESULTS: Mean difference between imaging
      modalities was 0.21 cm (+/-0.39 cm, p < 0.001). Limits of agreement were -0.55 to
      0.96 cm, exceeding clinical acceptability. Mean difference was higher and
      significant in group I (0.39 cm, p < 0.001) compared to group II (0.10 cm, p >
      0.05). Seventy-percent of group I patients had CT scans revealing diameters of
      >=5.5 cm. Inter-observer bias was not significant. CONCLUSION: Significant
      differences between imaging modalities, more in US diameters of below 5.5 cm,
      exist. We recommend AAAs measuring >=5 cm on US should undergo earlier referral
      to a vascular service and CT.

PMID- 21852166
TI  - CPMG echo amplitudes with arbitrary refocusing angle: explicit expressions,
      asymptotic behavior, approximations.
AB  - Exact explicit analytical expression for echoes in the Carr-Purcell-Meiboom-Gill
      sequence with arbitrary excitation and refocusing angles and resonance offset of
      RF pulses was obtained, employing the generating functions formalism developed
      earlier by authors. Asymptotic form and analytical approximation for echoes were
      derived in an elegant way and analyzed in details. In particular, it was shown
      that depending on T(1), T(2) and parameters of the pulse sequence, oscillatory
      behavior of echoes can take place. Accuracy of asymptotic forms and
      approximations were tested by comparison with exactly calculated echo amplitudes.
      Besides, it was shown, that the generating function approach can be applied to
      the consideration of terminated pulse sequences, when after-pulses echoes are
      registered.

PMID- 21852167
TI  - Longitudinal evaluation of bone mineral density and body composition in patients
      with positive celiac serology.
AB  - Untreated celiac disease is associated with lower bone mineral density (BMD),
      body weight and fat mass compared with controls. There are few longitudinal
      studies examining changes in body composition after celiac disease diagnosis. The
      aim of this study was to compare changes in BMD and body composition in celiac
      seropositive cases who had undergone baseline and follow-up dual energy x-ray
      absorptiometry (DXA) with seronegative controls. Celiac serologic and BMD
      databases for the Province of Manitoba, Canada, were linked. Endomysial antibody
      (EMA) seropositive cases and EMA seronegative controls over age 40 who had
      serologic testing within 6 months of DXA testing and a follow-up DXA were
      extracted from the databases. Changes in BMD, BMI and body composition were
      compared in the 2 groups. The 43 EMA seropositive cases had lower baseline spine
      and hip BMD, BMI and fat measurements compared with 233 EMA seronegative
      controls. For seropositive versus seronegative individuals there were greater
      increases in mean spine BMD (4.6%/year vs 0.7% spine, p < 0.0001), hip BMD (3.0
      %/year vs 0.2%/year hip, p < 0.0001), and body weight (2.8%/year vs 0.3%/year, p
      < 0.0001). Increases in mean abdominal fat (2.4%/year vs 0.4%/year, p < 0.0001)
      were also greater in seropositive versus seronegative individuals, while
      increases in hip fat were less marked (0.9%/year vs 0.3%/year, p = 0.0071). This
      longitudinal database study documents significant improvements in BMD in
      seropositive cases. BMI and fat measures also increased, with the abdominal fat
      compartment demonstrating the greatest increase. Further studies are needed to
      determine the clinical significance of this regional increase in abdominal fat.

PMID- 21852169
TI  - Effect of silicone gluteal implant on bone mineral density evaluation by DXA
      scan.

PMID- 21852168
TI  - Underestimated fracture probability in patients with unilateral hip
      osteoarthritis as calculated by FRAX.
AB  - Osteoporosis (OP) and osteoarthritis (OA) are age-related diseases often
      considered to be mutually exclusive. We previously found that 25% of women with
      advanced OA had occult OP and that femoral neck (FN) bone mineral density (BMD) T
      scores were significantly higher for osteoarthritic vs contralateral hips. The
      FRAX calculator incorporates clinical risk factors and FN BMD T-score to estimate
      10-yr total fracture probability and hip fracture probability. In 35 women and
      men aged 41 yr or older with unilateral hip OA scheduled for hip replacement, we
      tested whether FRAX fracture probability is underestimated when using data for
      the OA rather than the contralateral hip. There were between-hip differences for
      FN BMD T-score (p<0.0001), total fracture probability (p =0.0004), and hip
      fracture probability (p =0.0009). Use of FN BMD T-scores resulted in OP treatment
      recommendations for 0% and 11% of subjects compared with 11% and 17% for total
      fracture probability and hip fracture probability, respectively. In 6-11% of
      subjects in this series, the FRAX calculator underestimated fracture probability
      with data for the OA hip. With the increased use of FRAX in clinical use, these
      data suggest that measurement of BMD at the contralateral hip may yield higher
      calculated FRAX total and hip fracture probabilities.

PMID- 21852170
TI  - Rheumatoid arthritis is associated with less optimal hip structural geometry.
AB  - The overall goal of this study was to assess the longitudinal changes in bone
      strength in women reporting rheumatoid arthritis (RA; n=78) compared with
      nonarthritic control participants (n=4779) of the Women's Health Initiative bone
      mineral density (WHI-BMD) subcohort. Hip structural analysis program was applied
      to archived dual-energy X-ray absorptiometry scans (baseline, years 3, 6, and 9)
      to estimate bone mineral density (BMD) and hip structural geometry parameters in
      3 femoral regions: narrow neck (NN), intertrochanteric (IT), and shaft (S). The
      association between RA and hip structural geometry was tested using linear
      regression and random coefficient models. Compared with the nonarthritic control,
      the RA group had a lower BMD (p=0.061) and significantly lower outer diameter
      (p=0.017), cross-sectional area (p=0.004), and section modulus (p=0.035) at the
      NN region in the longitudinal models. No significant associations were seen at
      the IT regions or S regions, and the association was not modified by age,
      ethnicity, glucocorticoid use, or time. Within the WHI-BMD, women with RA group
      had reduced BMD and structural geometry at baseline, and this reduction was seen
      at a fixed rate throughout the 9 yr of study.

PMID- 21852171
TI  - E-mail-based symptomatic surveillance combined with self-collection of nasal
      swabs: a new tool for acute respiratory infection epidemiology.
AB  - OBJECTIVE: We examined the feasibility of combining communication by e-mail and
      self-collection of nasal swabs for the prospective detection of acute respiratory
      infections in a non-medical setting. METHODS: The study was conducted among a
      convenience sample of employees (n=53) at a research institution (December 2009
      April 2010). Real-time data on the occurrence of acute respiratory symptoms and a
      nasal self-swab were collected prospectively, with automated weekly e-mails as a
      reminder mechanism. Reverse transcription polymerase chain reaction (RT-PCR) was
      used to detect respiratory viral pathogens in the swabs. RESULTS: Fifty-one out
      of 53 participants completed the study. The study design was well accepted.
      Thirty (~57%) participants reported at least one episode of acute respiratory
      infection and returned the nasal swab during the study period (eight participants
      reported two episodes). The majority had no difficulties taking the self-swab and
      preferred this to swabbing by study personnel. Most participants obtained and
      returned the swabs within the recommended time. Viral respiratory pathogens were
      detected in 19 of 38 swabs (50%), with coronaviruses 229E/NL63 and OC43 and
      rhinoviruses A and B constituting 17 positive swabs (89%). CONCLUSIONS: Combining
      e-mail-based symptomatic surveillance with nasal self-swabbing promises to be a
      powerful tool for the real-time identification of incident cases of acute
      respiratory infections and the associated pathogens in population-based studies.

PMID- 21852172
TI  - [Which follow-up program after radiotherapy?].
AB  - Patients' follow-up after treatment represents a growing part of the radiation
      oncologist activity. Treatment effectiveness and morbidity are essential criteria
      to evaluate the quality of a clinical practice. Morbidity and mortality reviews
      and feedback experience meetings have been made mandatory. Post-treatment follow
      up has to be explicitly and formally organized. In the present article, we review
      the existing recommendations and consider several examples regarding frequently
      encountered cancers.

PMID- 21852173
TI  - On the impact of a dedicated educational program for ankylosing spondylitis:
      effect on patient satisfaction, disease knowledge and spinal mobility, a pilot
      study.

PMID- 21852174
TI  - The variability problem of normal human walking.
AB  - Previous investigations have suggested considerable inter-individual variability
      in the time course pattern of net joint moments during normal human walking,
      although the limited sample sizes precluded statistical analyses. The purpose of
      the present study was to obtain joint moment patterns from a group of normal
      subjects and to test whether or not the expected differences would prove to be
      statistically significant. Fifteen healthy male subjects were recorded on video
      while they walked across two force platforms. Ten kinematic and kinetic
      parameters were selected and input to a statistical cluster analysis to determine
      whether or not the 15 subjects could be divided into different 'families'
      (clusters) of walking strategy. The net joint moments showed a variability
      corroborating earlier reports. The cluster analysis showed that the 15 subjects
      could be grouped into two clusters of 5 and 10 subjects, respectively. Five
      parameters differed significantly, so the group of 5 subjects was characterized
      by (1) a higher peak knee joint extensor moment, (2) more flexed knee joint angle
      at heel strike, (3) during the whole stance phase, (4) lower peak knee joint
      flexor moment and (5) lower ankle joint angle at flat foot position. Calculation
      of bone-on-bone forces in the knee joint showed a value of 64 N/kg body weight in
      the K+ group and 55 N/kg in the K- group (p<0.05). It is unknown if differences
      of similar magnitude contribute to early joint degeneration in some individuals
      while not in others.

PMID- 21852175
TI  - Development and validation of a probe allowing accurate and continuous monitoring
      of location of squamo-columnar junction.
AB  - INTRODUCTION: Most pathology of the upper gastrointestinal tract now occurs close
      to the gastro-oesophageal squamo-columnar junction (SCJ). Studying the
      pathophysiology of this region even using high resolution pH, impedance and
      manometry is unreliable due to constant movement with respiration, swallowing and
      transient lower oesophageal sphincter relaxations. AIMS AND METHODS: A technique
      is reported allowing continuous real-time monitoring of the position of the SCJ.
      It involves endoscopically clipping a magnet (2 mm * 1 mm) to the SCJ and
      monitoring its position relative to a probe in the oesophago-gastric lumen. The
      latter has 26 Hall-Effect sensors mounted at 5mm spacing on a circuit board
      within a silicone tube. RESULTS: Bench studies: The recorded position of the
      magnet along the length of the probe was compared with its actual position.
      Accuracy was related to the distance between magnet and probe, orientation of the
      magnet relative to the probe and whether the magnet was anterior, posterior or
      lateral to the probe. Including all possible orientations of the magnet at or
      nearer than 10mm from the probe, the median accuracy along the length of probe
      was 2.4 mm (IQR 2.1 mm). The proportion of all possible orientations within 10mm
      of the probe giving an accuracy of +/-10 mm was 88.9%. In vivo studies: With
      simultaneous fluoroscopy, eight healthy subjects were asked to perform normal
      breathing, deep breathing, water swallows and finally advancement and retraction
      of probe over a 12 cm segment. The position recorded by fluoroscopy and probe at
      each second interval were compared. The correlation co-efficient for all 224
      position readings was 0.96 (95% CI: 0.89-0.96). No significant interference was
      observed when the probe was tested alongside high resolution pH and manometry.
      CONCLUSION: Used in conjunction with high resolution pH, impedance and manometry,
      this technique will allow for the first time detailed studies at the squamo
      columnar junction.

PMID- 21852176
TI  - Nonlinear heart rate dynamics: circadian profile and influence of age and gender.
AB  - Heart rate variability (HRV) is used as a marker of autonomic modulation of heart
      rate. Nonlinear HRV parameters providing information about the scaling behaviour
      or the complexity of the cardiac system were included. In addition, the chaotic
      behaviour was quantified by means of the recently developed numerical noise
      titration technique. 24h Holter recordings of a large healthy population (N=276,
      141 males, 18-71 years of age) were available. The goal was to investigate the
      influence of gender, age and day-night variation on these nonlinear HRV
      parameters. Numerical titration yielded similar information as other nonlinear
      HRV parameters do. However, it does not require long and cleaned data and
      therefore applicable on short (5min) noisy time series. A higher nonlinear
      behaviour was observed during the night (NLdr; day: 50.8+/-19.6%, night: 59.1+/
      19.5%; P<0.001) while nonlinear heart rate fluctuations decline with increasing
      age (NLdr; Pearson correlation coefficient r between -0.260 and -0.319 dependent
      on gender and day or night, all P<0.01). A clear circadian profile could be found
      for almost every parameter, showing in particular which changes occur during the
      transition phases of waking up and going to sleep. Our results support the
      involvement of the autonomic nervous system in the generation of nonlinear and
      complex heart rate dynamics.

PMID- 21852177
TI  - Secondary dystonia in a botulinum toxin clinic: clinical characteristics,
      neuroanatomical substrate and comparison with idiopathic dystonia.
AB  - The analysis of patients with secondary dystonia has been valuable to explore the
      anatomical, pharmacological and physiological bases of this disorder. The goal of
      this study is to compare the clinical characteristics of patients with primary
      and secondary dystonia and analyze the neuroanatomical bases of a subgroup of
      patients with lesion-induced dystonia. We identified patients evaluated in our
      Botulinum Toxin Clinic from 1/2000 to 7/2009 with an ICD code for "dystonia".
      Medical records of all subjects were reviewed, recording demographic, clinical,
      therapeutic and neuroimaging data. A total of 230 patients were included in the
      study. Idiopathic/primary dystonia was diagnosed in 162 and secondary dystonia in
      58, while in 10 the etiology was uncertain. We found a female predominance (2.4:1
      and 1.9:1 for primary and secondary dystonia, respectively). The cervical region
      was most commonly affected in primary dystonia and the limbs in secondary cases.
      The age at presentation was higher in primary (54.4 +/- 14.1) than secondary (49
      +/- 17.9) dystonia. Among patients with secondary dystonia, a focal lesion was
      the presumed etiology in 32, with localizing diagnostic studies available in 16.
      The most common lesions were strokes involving the corticospinal pathway. All of
      those patients exhibited limb dystonia, except one with cervical dystonia
      following a thalamic infarct. In conclusion, primary and secondary dystonias are
      more prevalent in women, suggesting a sex-related predisposition to the
      development of this movement disorder. Lesion-induced dystonia most frequently
      involves the limbs and is caused by lesions in the cerebral cortex and
      subcortical white matter.

PMID- 21852179
TI  - Automatic segmentation, internal classification, and follow-up of optic pathway
      gliomas in MRI.
AB  - This paper presents an automatic method for the segmentation, internal
      classification and follow-up of optic pathway gliomas (OPGs) from multi-sequence
      MRI datasets. Our method starts with the automatic localization of the OPG and
      its core with an anatomical atlas followed by a binary voxel classification with
      a probabilistic tissue model whose parameters are estimated from the MR images.
      The method effectively incorporates prior location, tissue characteristics, and
      intensity information for the delineation of the OPG boundaries in a consistent
      and repeatable manner. Internal classification of the segmented OPG volume is
      then obtained with a robust method that overcomes grey-level differences between
      learning and testing datasets. Experimental results on 25 datasets yield a mean
      surface distance error of 0.73 mm as compared to manual segmentation by
      experienced radiologists. Our method exhibits reliable performance in OPG growth
      follow-up MR studies, which are crucial for monitoring disease progression. To
      the best of our knowledge, this is the first method that addresses automatic
      segmentation, internal classification, and follow-up of OPG.

PMID- 21852178
TI  - An economic analysis of community-level fast food prices and individual-level
      fast food intake: a longitudinal study.
AB  - BACKGROUND: While dietary intake is shaped by cost, there is minimal research on
      the association between community-level food prices and dietary intake. METHODS:
      We used nationally representative, longitudinal data to examine how community
      level food price variation was associated with individual-level fast food intake
      by race/ethnicity and income across waves II (1996) and III (2001-2002) of the
      National Longitudinal Study of Adolescent Health (n=11,088) from 158 baseline and
      363 follow-up US counties. RESULTS: Negative binomial regression models
      predicting the number of fast food meals per week show strong relationships
      between fast food consumption and prices of fast food and soda that varied by
      gender and race/ethnicity. We found relatively stronger association between food
      prices and fast food intake for males and relatively greater price sensitivity
      for soda versus burgers. In the group with strongest associations (black males),
      a 20% increase in the price of soda was associated with a decrease of 0.25 visits
      to a fast food restaurant per week. CONCLUSIONS: Economic incentives may be an
      effective mechanism to address fast food intake in an age group at high risk for
      obesity.

PMID- 21852180
TI  - An image space approach to Cartesian based parallel MR imaging with total
      variation regularization.
AB  - The Cartesian parallel magnetic imaging problem is formulated variationally using
      a high-order penalty for coil sensitivities and a total variation like penalty
      for the reconstructed image. Then the optimality system is derived and
      numerically discretized. The objective function used is non-convex, but it
      possesses a bilinear structure that allows the ambiguity among solutions to be
      resolved technically by regularization and practically by normalizing a pre
      estimated norm of the reconstructed image. Since the objective function is convex
      in each single argument, convex analysis is used to formulate the optimality
      condition for the image in terms of a primal-dual system. To solve the optimality
      system, a nonlinear Gauss-Seidel outer iteration is used in which the objective
      function is minimized with respect to one variable after the other using an inner
      generalized Newton iteration. Computational results for in vivo MR imaging data
      show that a significant improvement in reconstruction quality can be obtained by
      using the proposed regularization methods in relation to alternative approaches.

PMID- 21852181
TI  - There is nothing paranormal about near-death experiences: how neuroscience can
      explain seeing bright lights, meeting the dead, or being convinced you are one of
      them.
AB  - Approximately 3% of Americans declare to have had a near-death experience. These
      experiences classically involve the feeling that one's soul has left the body,
      approaches a bright light and goes to another reality, where love and bliss are
      all encompassing. Contrary to popular belief, research suggests that there is
      nothing paranormal about these experiences. Instead, near-death experiences are
      the manifestation of normal brain function gone awry, during a traumatic, and
      sometimes harmless, event.

PMID- 21852182
TI  - A new modified fluorescein strip: Its repeatability and usefulness in tear film
      break-up time analysis.
AB  - PURPOSE: To (i) analyze the repeatability of fluorescein instillation from a
      modified fluorescein strip (MFS) compared to a standard fluorescein strip (FS),
      and to (ii) observe its usefulness in the measurement of the fluorescein break-up
      time (FBUT) in comparison to the Tearscope (NIBUT). METHODS: In-vitro: Intra- and
      inter-observer repeatability in fluorescein instillation from the MFS and FS was
      evaluated by fluorescence analysis (n=10, each). In-vivo: BUT of the right eye of
      20 randomly selected subjects (mean age 43.3+/-11.5, range=21-60 years, 8 males,
      12 females) was measured by use of the Tearscope and MFS. Subjects were grouped
      by the Ocular Surface Disease Index (OSDI) score into 8 OSDI+ and 12 OSDI- by a
      cut-off value of 15. RESULTS: In-vitro: Intra-observer 95% limit of agreement
      (LoA) of the MFS was similar to the FS LoA in observer 1 (O1), but better than
      the FS LoA in observer (O2) (MFS: O1: LoA=+/-1.98 mW; p=0.179; O2: +/-2.71;
      0.442; FS: O1: +/-1.71; 0.246; O2: +/-4.11; 0.512). Inter-observer LoA in
      fluorescence was better in MFS (+/-1.42; 0.111) than in FS (+/-3.71; 0.003). In
      vivo: MFS-BUT was significantly shorter than the NIBUT (p=0.002), but
      significantly correlated (r=0.864, p<0.001). NIBUT and MFS-BUT were significant
      discriminators (p<0.001) of OSDI+/-(0.948/8s and 0.938/5s [AUC/cut-off value];
      NIBUT and MFS-BUT, respectively). CONCLUSIONS: The MFS was better in the
      repeatability of fluorescein instillation than the FS. NIBUT and MFS-BUT were
      good discriminators of dry eye symptoms, but differ in their cut-off values.

PMID- 21852183
TI  - Molecular machines in archaeal DNA replication.
AB  - The archaeal DNA replication apparatus is a simplified version of that of
      eukaryotes and has attracted attention as a tractable model system for the
      orthologous, but significantly more complex eukaryal machinery. A variety of
      archaeal model organisms have been investigated with strong emphasis on
      structural and biochemical analyses of replication-associated proteins. In this
      review we will describe recent advances in understanding the properties of the
      replicative helicase, the MCM complex, and the role of the sliding clamp, PCNA,
      in mediating a range of protein-DNA transactions. Although both complexes form
      ring shaped assemblies, they play very distinct roles at the leading and trailing
      edges of the replication fork machinery respectively.

PMID- 21852184
TI  - Increased risk of stroke in young head and neck cancer patients treated with
      radiotherapy or chemotherapy.
AB  - BACKGROUND: Chemo-radiotherapy-induced carotid stenosis and cerebrovascular
      events in head and neck cancer patients can cause severe disability and death. We
      aimed to estimate the risk of stroke in such patients over a six-year follow-up
      period. PATIENTS AND METHODS: The study cohort consisted of head and neck cancer
      patients (n=10,172). Cox proportional hazard model was used to compare the stroke
      free survival rate between the patients treated with radiotherapy or
      chemotherapy, surgery alone, and surgery with adjuvant therapy after adjusting
      for possible confounding factors. RESULTS: At the end of follow-up, 384 patients
      had strokes: 126 (4.3%) from the surgery alone group, 167 (3.8%) from the
      radiotherapy or chemotherapy group, and 91 (3.2%) from the surgery with adjuvant
      therapy (P=0.222). Head and neck cancer patients aged less than 55 years treated
      with radiotherapy or chemotherapy conferred a 1.8-fold higher risk for stroke
      (95% CI, 1.22-2.56; P=0.003) after adjusting for patient characteristics, co
      morbidities, geographic region, urbanization level, and socio-economic status.
      There was no statistical difference in stroke risk between different treatment
      modalities in head and neck cancer patients aged 55 years and more. CONCLUSIONS:
      Young head and neck cancer patients treated with radiotherapy or chemotherapy
      have higher risks for stroke. Different treatment strategies should be considered
      in such patients.

PMID- 21852185
TI  - Distinct patterns of stomatitis with concurrent cetuximab and radiotherapy for
      head and neck squamous cell carcinoma.
AB  - To describe the distinct patterns of severe anterior stomatitis seen with
      concurrent cetuximab and radiotherapy (RT) compared to chemoRT or altered
      fractionation RT (AFRT) and explore potential associations with clinical and
      dosimetric parameters. We reviewed acute toxicity data from 42 patients receiving
      cetuximab-RT and a matched cohort of 36 patients receiving chemoRT or AFRT. The
      occurrence of grade >=3 oral toxicities was analysed with respect to clinical
      (age, gender, smoking/alcohol history, tumour subsite, grade of acneiform rash)
      and dosimetric parameters. Cetuximab-RT patients experienced higher rates of
      grade >=3 cheilitis (26% vs 6%, p=0.01) and anterior stomatitis (38% vs 6%,
      p=0.002), despite these structures receiving low RT doses (median maximum dose to
      lips 9.3 Gy, anterior oral cavity 20 Gy). Multivariable analyses identified
      increasing severity of acneiform rash as the strongest predictor of grade >=3
      cheilitis whilst increasing RT dose was weakly correlated. A trend was observed
      for increasing pack years of smoking on univariate analysis only. The combination
      of cetuximab and low doses of RT to the anterior oral cavity has resulted in a
      distinctive pattern of cheilitis and anterior stomatitis in our patients. Further
      exploration of this phenomenon may yield additional insights into the interaction
      of cetuximab with RT in non-target tissues.

PMID- 21852186
TI  - SERS detection of protein biochip fabricated by etching polystyrene template.
AB  - In this study, a nanoscale protein chip is prepared by using an etched
      polystyrene (PS) template. This protein chip can be directly used for
      immunoassay, with the help of Surface Enhanced Raman Scattering (SERS) spectra.
      Some glass slides submerged in aldehyde is initially prepared, modified with
      antibodies, human immunoglobulin G (IgG). Then PS arrays are self-assembled on
      these slides with the Langmuir-Blodgett method. The PS template pattern is
      transferred to the human IgG substrate using an etching process-slides are
      exposed to O(2) plasma for 90s. The PS nanoparticles are then washed away using
      phosphate buffered saline solution. Next, the slides are dipped into bovine serum
      albumin solution to ensure that the anti IgG would bond only to the human IgG. At
      this moment, a patterned protein chip is obtained. When used for protein
      detection, the protein chip could be immersed into labeled specificity antigen
      solution. Here we chose fluorescein isothiocyanate anti-human IgG. After washing,
      only bonded antigens remain. Fluorescence microscopy and SERS is used to
      characterize the samples. The SERS spectra intensity shows liner correlation with
      the concentration of anti-human IgG. All the experiments are conducted in a
      phosphate buffered saline solution at 37 degrees C for 2 h.

PMID- 21852187
TI  - Relationship between chemical structure and biological activity of alkali metal o
      , m- and p-anisates. FT-IR and microbiological studies.
AB  - In this work we investigated relationship between molecular structure of alkali
      metal o-, m-, p-anisate molecules and their antimicrobial activity. For this
      purpose FT-IR spectra for lithium, sodium, potassium, rubidium and caesium
      anisates in solid state and solution were recorded, assigned and analysed.
      Microbial activity of studied compounds was tested against Escherichia coli,
      Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris. In order to
      evaluate the dependency between chemical structure and biological activity of
      alkali metal anisates the statistical analysis (multidimensional regression and
      principal component) was performed for selected wavenumbers from FT-IR spectra
      and parameters that describe microbial activity of anisates. The obtained
      statistical equations show the existence of correlation between molecular
      structure of anisates and their biological properties.

PMID- 21852188
TI  - Theoretical study on contribution of charge transfer effect to surface-enhanced
      Raman scattering spectra of pyridine adsorbed on Ag(n) (n = 2-8) clusters.
AB  - We investigate surface-enhanced Raman scattering (SERS) spectra of pyridine-Ag(n)
      (n = 2-8) complexes by density functional theory (DFT) and time-dependent DFT
      (TDDFT) methods. In simulated normal Raman scattering (NRS) spectra, profiles of
      pyridine-Ag(n) (n = 2-8) complexes are analogical with that of isolated pyridine.
      Nevertheless, calculated pre-SERS spectra are strongly dependent on electronic
      transition states of new complexes. Wavelengths at 335 nm, 394.8 nm, 316.9 nm and
      342.6 nm, which are nearly resonant with pure charge transfer excitation states,
      are adopted as incident light when simulating pre-SERS spectra for pyridine-Ag(n)
      (n = 2-8) complexes, respectively. We obtain enhancement factors from 10(3) to
      10(5) in pre-SERS spectra compared with corresponding NRS spectra. The obvious
      increase in Raman intensities mainly result from charge transfer resonance Raman
      enhancement. A charge difference densities (CDDs) methodology is adopted in
      describing chemical enhancement mechanism. This methodology aims at visualizing
      charge transfer from Ag(n) (n = 2-8) clusters to pyridine on resonant electronic
      transition, which is one of the most direct evidences for chemical enhancement
      mechanism.

PMID- 21852189
TI  - Optical properties of sol-gel synthesized calcium doped ZnO nanostructures.
AB  - Optical properties of Ca doped ZnO nanoparticles prepared at room temperature
      through wet chemical method have been investigated. X-ray diffraction studies
      show that particles are crystalline in nature and doping did not induce impurity
      phases. Optical absorption measurements show an absorption peak at ~372 nm which
      is due to excitonic absorption of the ZnO. Photoluminescence studies reveal a
      broad emission at an excitation wavelength of 335 nm and the bands are attributed
      to near band edge emission, oxygen vacancies, surface dangling bonds and zinc
      interstitials. Incorporating Ca(2+) induces reduction in near band edge emission
      and there is an enhancement in the oxygen vacancy peaks which are attributed to
      the shape changes in the nanoparticles.

PMID- 21852190
TI  - Evoked potentials and quantitative thermal testing in spinal cord injury patients
      with chronic neuropathic pain.
AB  - OBJECTIVE: Neuropathic pain (NP) is a common symptom following spinal cord injury
      (SCI). NP may be associated with altered processing of somatosensory pathways in
      dermatomes rostral to the injury level. To explore this possibility, the
      characteristics of contact heat evoked potentials (CHEPs) and quantitative
      thermal testing (QTT) were studied at and above the lesion level in SCI patients
      with NP. The goal was to determine processing abnormalities correlated with data
      from clinical evaluations. METHODS: Thirty-two subjects with chronic NP, 22
      subjects without NP and 16 healthy control subjects were studied. Warm and heat
      pain thresholds were determined both at and above SCI level. CHEPs were recorded
      above SCI level and subjects rated their perception of evoked heat pain using a
      numerical rating scale. RESULTS: CHEPs were not different between the three
      groups. Evoked pain perception in SCI subjects with NP was significantly higher
      than in SCI subjects without NP and healthy controls. Heat pain threshold was
      significantly lower in subjects with NP in comparison to both groups.
      CONCLUSIONS: Our findings indicate that processing of somatosensory inputs from
      dermatomes rostral to the injury level is abnormal in SCI subjects with NP.
      SIGNIFICANCE: SCI somatosensory processing alteration may contribute to the
      understanding of the mechanisms underlying NP and secondary changes to NP in SCI.

PMID- 21852191
TI  - Multivessel coronary artery spasm.
AB  - Coronary spasm is increasingly recognised as an important aetiological mechanism
      causing myocardial ischaemia. Occasionally cases present with evidence of ST
      segment elevation myocardial infarction, usually secondary to spasm confined to a
      solitary coronary artery. We present the rare and life-threatening case of severe
      coronary spasm afflicting all three major epicardial arteries simultaneously. It
      describes the difficult emergency scenario and ongoing management dilemmas
      encountered by physicians confronted with multivessel coronary spasm. Moreover we
      discuss the malignant prognosis associated with this ailment and describe the
      potential insights provided by cardiac magnetic resonance imaging that might
      identify those at greatest risk after the index event.

PMID- 21852192
TI  - All is fair in virus-host interactions: NK cells and cytomegalovirus.
AB  - The infection of mice with mouse cytomegalovirus (MCMV) as a model of human
      cytomegalovirus (HCMV) infection has been particularly informative in elucidating
      the role of innate and adaptive immune response mechanisms during infection.
      Millions of years of co-evolution between cytomegaloviruses (CMV) and their hosts
      has resulted in numerous attempts to overwhelm each other. CMVs devote many genes
      to modulating the host natural killer (NK) cell response and NK cells employ many
      strategies to cope with CMV infection. While focusing on these attack
      counterattack measures, this review will discuss several novel mechanisms of
      immune evasion by MCMV, the role of Ly49 receptors in mediating resistance to
      MCMV, and the impact of the initial NK cell response on the shaping of adaptive
      immunity.

PMID- 21852193
TI  - Nurses' conceptions of how an alternative supervision model influences their
      competence in assessment of nursing students in clinical practice.
AB  - AIM: The aim of the study was to describe variations in clinical nurses'
      conceptions of how an alternative supervision model influences their competence
      in assessing nursing students in clinical practice. BACKGROUND: Nursing education
      programme in Norway includes 50 weeks of clinical studies. Due to changes in the
      education system and increased focus on evidence-based practice, alternative
      models of supervision and assessment have been developed. METHOD: The study has a
      qualitative and descriptive design using a phenomenographic approach. Informants
      were 49 clinical nurses from five different nursing homes. RESULTS: The clinical
      nurses' experiences are described through three description categories:
      'pressure', 'encouragement' and 'development'. The informants experienced demands
      from the University College and colleagues, but personal and professional
      development was encouraged through group supervision and written information from
      the University College. CONCLUSIONS: The alternative supervision model supported
      the clinical nurses in the assessment of the nursing students, and their role as
      educators. The alternative supervision model also seems to strengthen the
      relationship between field of practice and University College.

PMID- 21852194
TI  - Eliminating multiple pregnancies: an appropriate target for government
      intervention?
AB  - The manuscript in this issue of the journal by Bissonette et al. reports on a new
      government-sponsored intervention into the practice of IVF within the province of
      Quebec, Canada, which in the authors' opinion highly successfully reduced
      twinning rates, while maintaining overall acceptable pregnancy rates. Given the
      opportunity to comment, their manuscript, in my opinion, only reemphasizes why,
      despite wide professional support, the concept of single embryo transfer (SET)
      is: (i) damaging to most infertility patients by reducing pregnancy chances; (ii)
      does so without compensatory benefits; (iii) impinges on patients' rights to self
      determination; (iv) has significant negative impact on IVF-generated birth rates;
      and (v) thus, demonstrating, once more, that governments should not interfere
      with the patient-physician relationships.

PMID- 21852195
TI  - Measurement properties of psychosocial and environmental measures associated with
      fruit and vegetable intake among middle school adolescents.
AB  - OBJECTIVE: To assess the measurement properties of several scales modified or
      created to assess factors related to fruit and vegetable intake within a young
      adolescent population. DESIGN: Cross-sectional with data collected via self
      report. SETTING: Data were collected in regularly scheduled classes in the school
      setting. PARTICIPANTS: African American and Caucasian middle school students
      (ages 11-15 years). VARIABLES MEASURED: Self-efficacy, modeling, outcome
      expectations, normative beliefs, parental food management practices, and
      influences on food choice. ANALYSIS: Pearson correlations, factor analysis, and
      Cronbach alpha. RESULTS: Subscales with adequate to good internal consistencies
      (0.65-0.88) were established. Fruit and vegetable intake was significantly
      correlated with self-efficacy, parent and peer modeling, family and peer
      normative beliefs, and social and health outcome expectations. Fruit and
      vegetable intake was not significantly correlated with permissive eating, food
      self-preparation, or the 3 subscales measuring influences on food choice (social
      influence, avoiding weight-gain food, and appeal and access). CONCLUSIONS AND
      IMPLICATIONS: These measures, most originally developed for children and adults
      and modified for this study, demonstrated adequate measurement properties for an
      adolescent sample.

PMID- 21852196
TI  - Psychosocial outcomes of Lunch is in the Bag, a parent program for packing
      healthful lunches for preschool children.
AB  - OBJECTIVE: This pilot study evaluated effects of Lunch is in the Bag on
      behavioral constructs and their predictive relationship to lunch-packing
      behaviors of parents of young children. METHODS: Six child care centers were pair
      matched and randomly assigned to intervention (n = 3) and comparison (n = 3)
      groups. Parent/child dyads participated. Constructs of knowledge, outcome
      expectations, perceived control, subjective norms, and intentions were measured
      by a pre/post questionnaire. Hierarchical linear regression was used, and P < .05
      was considered significant. RESULTS: There were significant increases in
      knowledge (P = .01); outcome expectations for whole grains (P < .001); and
      subjective norms for fruit (P = .002), vegetables (P = .046), and whole grains (P
      = .02). Perceived control, outcome expectations, and intentions significantly
      predicted packing vegetables and knowledge predicted whole grains. CONCLUSIONS
      AND IMPLICATIONS: Lunch is in the Bag is a feasible intervention to improve the
      lunch-packing behaviors of parents of preschool-aged children.

PMID- 21852197
TI  - Arguments at mealtime and child energy intake.
AB  - OBJECTIVE: To examine how arguments at mealtimes relate to children's daily
      energy intake. DESIGN: A cross-sectional study using data obtained through the
      Quebec Longitudinal Study of Child Development 1998-2010 (QLSCD), a
      representative sample of children born in 1998, in the province of Quebec,
      Canada. SETTING: Face-to-face interviews, questionnaires, and 24-hour dietary
      recall interviews addressed to children's parents. PARTICIPANTS: One thousand
      five hundred forty-nine 4-year-old children who participated in a nutrition
      substudy. MAIN OUTCOME MEASURE: Children's energy intakes were measured through a
      24-hour dietary recall interview administered to parents by trained
      nutritionists, in the children's homes. ANALYSIS: The main associations were
      examined through chi-square tests of independence and through multivariate
      logistic regression analyses. RESULTS: The adjusted odds for consuming a high
      daily energy intake was 2.5 (95% confidence interval: 1.3-4.9) in children who
      were never exposed to arguments (between parents and children) at mealtimes, in
      comparison to children who were often or always exposed to arguments. CONCLUSIONS
      AND IMPLICATIONS: Mealtimes that are free of arguments, specifically between
      parents and children, appear to associate with high daily energy intakes in
      children, even after controlling for other factors, including a child's level of
      physical activity, eating in front of the television, mother's educational level,
      and number of overweight parents, among others.

PMID- 21852198
TI  - Neurologists' and neurology residents' knowledge of issues related to pregnancy
      for women with epilepsy.
AB  - We aimed to assess physician knowledge for 2009 guidelines established by the
      American Academy of Neurology and American Epilepsy Society regarding issues
      related to pregnancy for women with epilepsy. A questionnaire was developed and
      distributed to all neurologists and neurology residents practicing in a large
      Canadian health region serving a population of 1.4 million. Descriptive
      statistics were obtained and percentage of correct responses was calculated.
      Forty-five physicians completed the survey (response rate = 83.3%), with a median
      correct score of 50%. Residents were more likely (93.3%) to state that this
      information was important to their practice than staff physicians (40.0%).
      Overall knowledge of outcomes associated with specific AEDs was poor; less than
      half of the physicians correctly indicated which AEDs were associated with
      adverse outcomes for the majority of drug-related questions. We recommend
      multifaceted, interactive implementation strategies for increasing knowledge of
      guideline contents.

PMID- 21852199
TI  - Brain damage and IQ in unilateral Sturge-Weber syndrome: support for a "fresh
      start" hypothesis.
AB  - We tested the hypothesis that extent of severe hypometabolism measured by
      fluorodeoxyglucose PET has a U-shaped (nonlinear) relationship to IQ in children
      with unilateral Sturge-Weber syndrome. Thirty-five consecutive children (age
      range: 30-153 months) with Sturge-Weber syndrome and unilateral brain involvement
      were enrolled in the study. Participants underwent cognitive assessment and
      interictal fluorodeoxyglucose PET scans. Regression analyses tested whether a
      quadratic model best accounted for the relationship between extent of severe
      cortical hypometabolism and IQ, controlling for seizure variables. A significant
      quadratic relationship was found between IQ and extent of severe (but not total)
      hypometabolism. Seizure variables also contributed significant variance to
      cognitive functions. Results suggest that intermediate size of severe hemispheric
      hypometabolism is associated with the worst cognitive outcomes, and small or
      absent lesions, with the best cognitive outcomes. Children in whom a very large
      extent of the hemisphere is severely affected are likely to have relatively
      preserved cognitive function.

PMID- 21852200
TI  - Differential neuroprotection by A(1) receptor activation and A(2A) receptor
      inhibition following pilocarpine-induced status epilepticus.
AB  - Aiming at a better understanding of the role of A(2A) in temporal lobe epilepsy
      (TLE), we characterized the effects of the A(2A) antagonist SCH58261 (7-(2
      phenylethyl)-5-amino-2(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine)
      on seizures and neuroprotection in the pilocarpine model. The effects of SCH58261
      were further analyzed in combination with the A(1) agonist R-Pia (R(-)-N(6)-(2)
      phenylisopropyl adenosine). Eight groups were studied: pilocarpine (Pilo),
      SCH+Pilo, R-Pia+Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, and R
      Pia+SCH+Saline. The administration of SCH58261, R-Pia, and R-Pia+SCH58261 prior
      to pilocarpine increased the latency to SE, and decreased either the incidence of
      or rate of mortality from SE compared with controls. Administration of R-Pia and
      R-Pia+SCH58261 prior to pilocarpine reduced the number of Fluoro-Jade B-stained
      cells in the hippocampus and piriform cortex when compared with control. This
      study showed that pretreatment with R-Pia and SCH58261 reduces seizure
      occurrence, although only R-Pia has neuroprotective properties. Further studies
      are needed to clarify the neuroprotective role of A(2A) in TLE.

PMID- 21852203
TI  - Recent insights into the regulation of breathing.
AB  - This mini review highlights recent research on the control of breathing that
      places gliotransmission and purinergic signaling as core drivers to the
      respiratory circuits in the brainstem. These elements underpin transduction of
      hypercapnia, hypoxia and acid sensing at central and peripheral chemoreceptors.
      The processes involve propagation of an extracellular ATP signal and associated
      P2 receptor activation, where ATP acts on both the glial cells and the associated
      output cells in the sensor complex - the respiratory rhythm generator neurons and
      the ventral inspiratory pre-motor neurons. At the peripheral carotid
      chemoreceptor, the hypoxia sensor likely involves the gasotransmitter H(2)S,
      complemented by purinergic neurotransmission.

PMID- 21852201
TI  - The Msx1 Homeoprotein Recruits Polycomb to the Nuclear Periphery during
      Development.
AB  - Control of gene expression during development requires the concerted action of
      sequence-specific transcriptional regulators and epigenetic modifiers, which are
      spatially coordinated within the nucleus through mechanisms that are poorly
      understood. Here we show that transcriptional repression by the Msx1 homeoprotein
      in myoblast cells requires the recruitment of Polycomb to target genes located at
      the nuclear periphery. Target genes repressed by Msx1 display an Msx1-dependent
      enrichment of Polycomb-directed trimethylation of lysine 27 on histone H3
      (H3K27me3). Association of Msx1 with the Polycomb complex is required for
      repression and regulation of myoblast differentiation. Furthermore, Msx1 promotes
      a dynamic spatial redistribution of the H3K27me3 repressive mark to the nuclear
      periphery in myoblast cells and the developing limb in vivo. Our findings
      illustrate a hitherto unappreciated spatial coordination of transcription factors
      with the Polycomb complex for appropriate regulation of gene expression programs
      during development.

PMID- 21852204
TI  - A wide methodological approach to identify a large duplication in CFTR gene in a
      CF patient uncharacterised by sequencing analysis.
AB  - BACKGROUND: PCR-based diagnostic procedures are not able to characterise 6% of CF
      alleles. Recently, the application of array-CGH and of CFTR mRNA analysis has
      allowed the identification of new copy number mutations and splicing defects,
      that account for 2% and 13% of CF alleles, respectively, in the Italian
      population. METHODS: Here, we report the characterisation of a large duplication
      in CFTR gene through different methods: MLPA assay, RT-PCR and high-resolution
      array-CGH. RESULTS: We identified a large duplication, involving exons 6b-16, in
      a patient heterozygous for F508del mutation. This duplication produces an
      abnormal transcript with an out of frame addition of 2244 nucleotides and leads
      to the insertion of 8 amino-acid residues in the protein, followed by a stop
      codon. CONCLUSIONS: We propose a wide methodological approach based on MLPA
      assay, RT-PCR and high-resolution array-CGH to routinely analyse CF patients
      uncharacterised for one or both CFTR alleles.

PMID- 21852205
TI  - Normal total and high molecular weight adiponectin levels in adults with cystic
      fibrosis.
AB  - Cystic fibrosis related diabetes (CFRD) is an important complication of CF that
      increases mortality. Adiponectin, an adipokine secreted from adipose tissue,
      plays an important role in fatty acid and glucose metabolism. Lower total
      adiponectin (TA) levels have been linked to the risk of developing type 2
      diabetes. However, studies show that the high molecular weight isoform (HMW),
      thought to be more active than TA, might be a better indicator of insulin
      sensitivity. Our aim was to determine the association between HMW and insulin
      sensitivity in CF subjects and determine if other factors might modulate its
      levels. Thirteen control subjects and 47 CF adults (16 with normal glucose
      tolerance, 16 prediabetic and 15 with CFRD) underwent an oral glucose tolerance
      test. Blood samples were taken at time 0, 30, 60, 90 and 120 min. Body mass
      index, fibrinogen, glucose and insulin, TA and HMW were measured in every
      subject. Regression analysis was used to determine the association between TA,
      HMW and glucose (fasting glucose, 2h glucose and glucose AUC) as well as insulin
      (fasting insulin, insulin AUC, and Stumvoll insulin sensitivity index)
      parameters. TA and HMW levels were similar between CF patients and controls and
      were not associated to insulin sensitivity. TA was negatively associated to
      insulin AUC (p=0.0108) and 2h glucose (p=0.0116) in controls while these
      relationships were either weakly negative (p=0.0208) or weakly positive
      (p=0.0105) in CF patients. Also, HMW was negatively associated to insulin
      (p=0.00301) and glucose AUC (p=0.0546) in controls whereas these associations
      were positive in CF patients (p=0.0388, p=0.0232 respectively). In conclusion,
      our exploratory study on HMW adiponectin demonstrated similar levels of TA and
      HMW between CF patients and controls and different relationships between forms of
      adiponectin to glucose metabolism and insulin in CF.

PMID- 21852206
TI  - Quantitative urine amino acid analysis using liquid chromatography tandem mass
      spectrometry and aTRAQ reagents.
AB  - Ion-exchange chromatography (IEC) is the most widely used method for amino acid
      analysis in physiological fluids because it provides excellent separation and
      reproducibility, with minimal sample preparation. The disadvantage, however, is
      the long analysis time needed to chromatographically resolve all the amino acids.
      To overcome this limitation, we evaluated a novel liquid chromatography tandem
      mass spectrometry (LC-MS/MS) method, which utilizes aTRAQ reagents, for amino
      acid analysis in urine. aTRAQ reagents tag the primary and secondary amino groups
      of amino acids. Internal standards for each amino acid are also labeled with a
      modified aTRAQ tag and are used for quantification. Separation and identification
      of the amino acids is achieved by liquid chromatography tandem mass spectrometry
      using retention times and mass transitions, unique to each amino acid, as
      identifiers. The run time, injection-to-injection, is 25 min, with all amino
      acids eluting within the first 12 min. This method has a limit of quantification
      (LOQ) of 1 MUmol/L, and is linear up to 1000 MUmol/L for most amino acids. The
      Coefficient of Variation (CV) was less than 20% for all amino acids throughout
      the linear range. Method comparison demonstrated concordance between IEC and LC
      MS/MS and clinical performance was assessed by analysis of samples from patients
      with known conditions affecting urinary amino acid excretion. Reference intervals
      established for this method were also concordant with reference intervals
      obtained with IEC. Overall, aTRAQ reagents used in conjunction with LC-MS/MS
      should be considered a comparable alternative to IEC. The most attractive
      features of this methodology are the decreased run time and increased
      specificity.

PMID- 21852207
TI  - Design of ionic liquids for lipase purification.
AB  - Aqueous two-phase systems (ATPS) are considered as efficient downstream
      processing techniques in the production and purification of enzymes, since they
      can be considered harmless to biomolecules due to their high water content and
      due to the possibility of maintaining a neutral pH value in the medium. A recent
      type of alternative ATPS is based on hydrophilic ionic liquids (ILs) and salting
      out inducing salts. The aim of this work was to study the lipase (Candida
      antarctica lipase B - CaLB) partitioning in several ATPS composed of ionic
      liquids (ILs) and inorganic salts, and to identify the best IL for the enzyme
      purification. For that purpose a wide range of IL cations and anions, and some of
      their combinations were studied. For each system the enzyme partitioning between
      the two phases was measured and the purification factors and enzyme recoveries
      were determined. The results indicate that the lipase maximum purification and
      recovery were obtained for cations with a C(8) side alkyl chain, the [N(CN)(2)]
      anion and ILs belonging to the pyridinium family. However, the highest
      purification parameters were observed for 1-methyl-3-octylimidazolium chloride
      [C(8)mim]Cl, suggesting that the IL extraction capability does not result from a
      cumulative character of the individual characteristics of ILs. The results
      indicate that the IL based ATPS have an improved performance in the lipase
      purification and recovery.

PMID- 21852208
TI  - The function of soliton on bio-energy transport in the protein molecules: comment
      on "The theory of bio-energy transport in the protein molecules and its
      properties" by Xiao-feng Pang.

PMID- 21852210
TI  - Endoscopic diagnosis of hookworm-induced intestinal bleeding.

PMID- 21852211
TI  - Management of pregnancy and delivery in women with inherited bleeding disorders.
AB  - Women with inherited bleeding disorders present a wide spectrum of clinical
      symptoms that vary from mild or moderate bleeding tendency to severe episodes.
      Monthly haemostatic changes affect these women during menstruation and ovulation.
      These events may be associated with significant bleeding and pain leading to the
      limitations in conducting daily activities and adverse effect on quality of life.
      Likewise, pregnancy and delivery are critical times for affected women. During
      pregnancy, they may be at greater risk of miscarriage and bleeding complications.
      In particular, recurrent miscarriage was observed in women with type 3 von
      Willebrand disease, afibrinogenaemia and severe factor XIII deficiency, and an
      optimal therapeutic plan is required during their pregnancy. Precautions must be
      taken at delivery in these women, since they could be at risk of bleeding. The
      lack of adequate information makes it very difficult to prepare evidence-based
      guidelines for the prevention of bleedings in affected women and their treatment.
      A multidisciplinary team of obstetricians, haematologists and paediatricians is
      required with a good knowledge of these disorders and an awareness of the
      potential maternal neonatal complications.

PMID- 21852209
TI  - p53: guardian of ploidy.
AB  - Aneuploidy, often preceded by tetraploidy, is one of the hallmarks of solid
      tumors. Indeed, both aneuploidy and tetraploidy are oncogenic occurrences that
      are sufficient to drive neoplastic transformation and cancer progression. True to
      form, the tumor suppressor p53 obstructs propagation of these dangerous
      chromosomal events by either instigating irreversible cell cycle arrest or
      apoptosis. The tumor suppressor Lats2, along with other tumor inhibitory proteins
      such as BRCA1/2 and BubR1, are central to p53-dependent elimination of tetraploid
      cells. Not surprisingly, these proteins are frequently inactivated or
      downregulated in tumors, synergizing with p53 inactivation to establish an
      atmosphere of "tolerance" for a non-diploid state.

PMID- 21852212
TI  - Focus on perioperative management of anticoagulants and antiplatelet agents in
      spine surgery.
AB  - Perioperative management of anticoagulants and antiplatelet agents is based on a
      compromise between the risk of hemorrhage induced by maintaining (or substituting
      for) them and the risk of thrombosis if they are discontinued. The hemorrhage
      risk in major spinal surgery is clear (50-81% incidence of transfusion), and the
      incidence of postoperative symptomatic spinal hematoma varies between 0.4% and
      0.2% depending on whether low-molecular-weight heparin (LMWH) is prescribed
      postoperatively. The French Health Authority, in 2008, published guidelines on
      the management of patients treated with vitamin K antagonists. Treatment may be
      stopped without preoperative replacement in certain cases of atrial fibrillation
      or venous thromboembolic disease; otherwise, preoperative replacement by curative
      dose unfractionated heparin (UFH) or LMWH is recommended, with withdrawal early
      enough to avoid peroperative bleeding. Postoperative care should take account of
      hemorrhagic risk following surgery. The management of patients treated with
      antiplatelets is delicate, as maintenance is preferable in most of the situations
      in which they are prescribed (bare or active stenting, or secondary prevention of
      myocardial infarction, stroke or peripheral ischemia), although they are liable
      to increase the risk of perioperative hemorrhage, especially when associated to
      antithrombotic prophylaxis. If surgery cannot be performed under treatment
      continuation, the interruption should be as short as possible. New guidelines are
      presently being drawn up under the auspices of the French Health Authority. In
      both types of treatment, the strategy should be jointly determined by surgeon,
      anesthesiologist and cardiologist, to optimize individualized care taking account
      of each party's requirements, with the patient in the central role. The selected
      strategy should be clearly stated in the patient's file. LEVEL OF EVIDENCE: V.

PMID- 21852213
TI  - Comments on: "Pneumorachis: A possible source of traumatic cord compression" by
      M. Ould-Slimane, M.-A. Ettori, J.-Y. Lazennec, H. Pascal-Moussellard, Y. Catonne
      and M.-A. Rousseau, published in Orthopaedics & Traumatology: Surgery & Research
      2010;96:825-8.

PMID- 21852216
TI  - High cancer mortality rates in the elderly in the UK.
AB  - INTRODUCTION: Cancer is largely a disease of older individuals. We compared UK
      cancer mortality rates with those for other countries to assess progress.
      METHODS: Death details were obtained from the WHO Mortality Database for the UK,
      the USA and 11 European countries. Mortality rates were calculated for the age
      groups 55-64, 65-74, 75-84 and >=85 years. Trends between 1995-97 and 2003-05
      were determined. The number of excess cancer deaths in the UK was calculated by
      applying the age-specific mortality rates observed in other regions to the UK.
      RESULTS: For all cancers combined, UK rates for 2003-05 in those aged >=75 years
      were 11-31% higher than in other regions. From 1995-97 to 2003-05, UK rates
      decreased by 16-17% in those aged <75 years, but increased by 2% in those >=85
      years compared with decreases of 4-16% for the other geographic areas. More than
      14,000 cancer deaths in the UK in those aged >=75 years would be avoided each
      year if UK mortality rates were identical to those in the USA. CONCLUSION: The UK
      is making poor progress in controlling cancer in older age groups. The gap in
      mortality rates between the UK and other countries and between old and young in
      the UK is widening.

PMID- 21852217
TI  - Insulin-like growth factor axis gene polymorphisms modify risk of pancreatic
      cancer.
AB  - OBJECTIVE: Insulin-like growth factor (IGF)-axis genes plays a critical role in
      cancer development and progression via their impact on the RAS/MAPK/ERK and
      PI3K/AKT/mTOR signaling pathways. We hypothesized that IGF-axis genetic variants
      modify individual susceptibility to pancreatic cancer. METHODS: We
      retrospectively genotyped 41 single-nucleotide polymorphisms of 10 IGF-axis genes
      (IGF1, IGF2, IGF1R, IGF2R, IGFBP1, IGFBP3, IGFBP5, IRS1, IRS2, and IRS4) in 706
      pancreatic cancer patients and 706 cancer-free controls using Sequenom and TaqMan
      technology. The association between genotype and pancreatic cancer risk was
      evaluated using multivariate logistic regression. A P value <=.007 at a false
      discovery rate of 10% was set as the significance level. RESULTS: We observed
      that the IGF1 *10212C>A and Ex4+2776G>A and IGF1R IVS2-70184A>G and IVS2+46329T>C
      variant genotypes were significantly associated with decreased pancreatic cancer
      risk (odds ratio [OR] range, 0.60-0.75) and that IGFBP1 Ex4+111A>G (I253M) was
      significantly associated with increased pancreatic cancer risk (OR=1.46) after
      adjusted for other risk factors and multiple comparisons (P<=.007). IGF2R and
      IGFBP3 variant haplotypes were associated with increased and decreased pancreatic
      cancer risk, respectively (P<.001). We also observed a weak interaction of the
      IGF1R IVS2+46329T>C and IGF2R Ex45+11C>T (L2222L) genotypes with diabetes
      (P(interaction)=.05) and interaction of IGF2R and IRS1 genotypes with alcohol
      consumption (P(interaction)=.03 and .019, respectively) on increased pancreatic
      cancer risk. CONCLUSION: These findings support our hypothesis that polymorphic
      variants of IGF-axis genes act alone or jointly with other risk factors to affect
      susceptibility to pancreatic cancer.

PMID- 21852218
TI  - Hormonal and reproductive factors and risk of postmenopausal thyroid cancer in
      the NIH-AARP Diet and Health Study.
AB  - BACKGROUND: Worldwide, thyroid cancer incidence rates are higher among women than
      men. While this suggests a possible etiologic role of female sex hormones, clear
      associations between hormonal and reproductive factors and thyroid cancer have
      not been observed. However, few large prospective studies have been conducted.
      METHODS: Hazard ratios (HRs) and 95% confidence intervals (CIs) for hormonal and
      reproductive factors and incident thyroid cancer were estimated using Cox
      regression methods in the prospective US NIH-AARP Diet and Health Study. Between
      1995 and 2006, 312 first primary incident thyroid cancers were diagnosed among
      187,865 postmenopausal women ages 50-71 at baseline. RESULTS: Thyroid cancer was
      not associated with ages at menarche or menopause, menopause type, or parity.
      Oral contraceptive use for >=10 years (vs. never use) was inversely associated
      with thyroid cancer risk (HR, 0.48; 95%CI, 0.28-0.84; P(trend)=0.01). Women who
      reported current menopausal hormone therapy at baseline had an increased thyroid
      cancer risk vs. never users (HR 1.38; 95% CI: 1.07-1.79) but there was no trend
      with increasing duration of use. Women with benign breast disease (BBD) had a
      significantly higher thyroid cancer risk vs. women without BBD (HR, 1.47; 95% CI,
      1.09-1.99). CONCLUSIONS: Our results do not support a strong role for female
      hormonal and reproductive factors including ages at menarche and menopause, type
      of menopause or parity, in thyroid cancer etiology among postmenopausal women.
      Compared with previous studies, no clear patterns emerge for exogenous hormone
      use but further analysis in large, prospective populations may be informative.
      The HR for BBD is consistent with the one previous prospective analysis that
      examined this association.

PMID- 21852219
TI  - Investigating the completeness of a histopathological cancer registry: estimation
      by capture-recapture analysis in a French geographical unit Alpes-Maritimes,
      2008.
AB  - INTRODUCTION: Cancer population studies require reliable and complete baseline
      data, which should theoretically be available by collecting histopathology
      records. The completeness of such a collection was evaluated using capture
      recapture analysis based on three data sources concerning breast and colorectal
      cancers over an identical period and within the same geographical area. METHOD:
      The total number of breast and colon cancer cases was estimated using capture
      recapture analysis based on the number of cases which were common or not between
      sources recording screened, diagnosed and treated cancers in the French Alpes
      Maritimes district. RESULT: The estimated total number of new cases of breast
      cancer diagnosed among Alpes Maritimes residents women aged 50-75 was 791 (95%
      CI: 784-797) in 2008. Of these 791 cases, 729 were identified through
      histopathology records, thus amounting to 92.2% completeness (95% CI: 91.5
      93.0%). The total estimated number of new cases of colorectal cancer diagnosed
      among Alpes Maritimes residents aged 50-75 was 527 (95% CI: 517-536). Of these
      527 cases, 481 were identified through histopathology records, thus amounting to
      91.3% completeness (95% CI: 89.7-93.0%). CONCLUSION: The estimated completeness
      of cancer records collected from histopathology laboratories was higher than 90%
      for new cases of breast and colorectal cancer within the age range concerned by
      the screening programme. A verified and validated histopathology data collection
      may be useful for cancer population studies.

PMID- 21852220
TI  - Measuring care and comfort in children with cerebral palsy: the care and comfort
      caregiver questionnaire.
AB  - OBJECTIVE: To evaluate the psychometric properties of the Care and Comfort
      Caregiver Questionnaire (CareQ), which was developed to measure the perceived
      effort of caregivers in providing care for children with moderate to severe
      cerebral palsy (CP). DESIGN: Cross-sectional data collection from a
      representative sample of a large racially/ethnically diverse geographic region.
      SETTING: Outpatient CP clinics at a metropolitan rehabilitation institution.
      PARTICIPANTS: A total of 100 primary caregivers of children with CP whose Gross
      Motor Function Classification System (GMFCS) levels were III-V. METHODS: The
      CareQ was administered to primary caregivers of children with CP. Internal
      consistency of the CareQ and its 3 domains (Personal Care, Positioning/Transfers,
      and Comfort) were evaluated with the Cronbach alpha. Construct validity of the
      CareQ was evaluated by its correlation with the Pediatric Functional Independence
      Measure (WeeFIM). Associations between CareQ scores and child and caregiver
      characteristics were assessed. RESULTS: Mean CareQ scores for children with GMFCS
      levels III, IV, and V were 30.6, 42.8, and 45.1, respectively (P < .01). The
      Cronbach alpha was 0.90 for total CareQ and 0.93, 0.80, and 0.82 for its Personal
      Care, Positioning/Transfers, and Comfort domains, respectively. Total CareQ and
      WeeFIM scores were negatively correlated (r = -.22; P = .03). Total CareQ scores
      were positively correlated with the child's age (r = .38; P < .01) and with body
      weight (r =.37; P < .01); however, no caregiver characteristics were associated
      with CareQ scores. CONCLUSIONS: The CareQ is a concise and internally consistent
      measure of difficulty of care as perceived by caregivers of children whose GMFCS
      levels were III-V. Further investigation should include assessment of
      responsiveness of the CareQ to changes in the child's functional status over time
      and/or with rehabilitation interventions.

PMID- 21852221
TI  - Investigating the role of feedback and motivation in clinical reaction time
      assessment.
AB  - OBJECTIVE: To investigate the influence of performance feedback and motivation
      during 2 tests of simple visuomotor reaction time (RT). DESIGN: Cross-sectional,
      observational study. SETTING: Outpatient academic physiatry clinic. PARTICIPANTS:
      Thirty-one healthy adults (mean [SD], 54 +/- 15 years). METHODS: Participants
      completed a clinical test of RT (RT(clin)) and a computerized test of RT with and
      without performance feedback (RT(compFB) and RT(compNoFB), respectively) in
      randomly assigned order. They then ranked their degree of motivation during each
      test. RT(clin) measured the time required to catch a suspended vertical shaft by
      hand closure after release of the shaft by the examiner. RT(compFB) and
      RT(compNoFB) both measured the time required to press a computer key in response
      to a visual cue displayed on a computer monitor. Performance feedback (visual
      display of the previous trial and summary results) was provided for RT(compFB),
      but not for RT(compNoFB). MAIN OUTCOME MEASUREMENTS: Means and standard
      deviations of RT(clin), RT(compFB), and RT(compNoFB) and participants' self
      reported motivation on a 5-point Likert scale for each test. RESULTS: There were
      significant differences in both the means and standard deviations of RT(clin),
      RT(compFB), and RT(compNoFB) (F(2,60) = 81.66, P < .0001; F(2,60) = 32.46, P <
      .0001, respectively), with RT(clin) being both the fastest and least variable of
      the RT measurements. RT(clin) was more strongly correlated with RT(compFB) (r =
      0.449, P = .0011) than with RT(compNoFB) (r = 0.314, P = .086). The participants
      reported similar levels of motivation between RT(clin) and RT(compFB), both of
      which were reported to be more motivating than RT(compNoFB). CONCLUSIONS: The
      stronger correlation between RT(clin) and RT(compFB) as well as the higher
      reported motivation during RT(clin) and RT(compFB) testing suggest that
      performance feedback is a positive motivating factor that is inherent to RT(clin)
      testing. RT(clin) is a simple, inexpensive technique for measuring RT and appears
      to be an intrinsically motivating task. This motivation may promote faster, more
      consistent RT performance compared with currently available computerized
      programs, which do not typically provide performance feedback.

PMID- 21852223
TI  - The "Von Meyenburg complex": an unusual cause of cholangitis?
AB  - Von Meyenburg complexes are an unusual incidental finding at radiologic or
      pathologic evaluation of patients with suspected liver disease. We present a case
      report of a patient with recurrent septic episodes in whom von Meyenburg
      complexes were eventually diagnosed and discuss available literature on this
      topic.

PMID- 21852222
TI  - Conversion of mouse and human fibroblasts into functional spinal motor neurons.
AB  - The mammalian nervous system comprises many distinct neuronal subtypes, each with
      its own phenotype and differential sensitivity to degenerative disease. Although
      specific neuronal types can be isolated from rodent embryos or engineered from
      stem cells for translational studies, transcription factor-mediated reprogramming
      might provide a more direct route to their generation. Here we report that the
      forced expression of select transcription factors is sufficient to convert mouse
      and human fibroblasts into induced motor neurons (iMNs). iMNs displayed a
      morphology, gene expression signature, electrophysiology, synaptic functionality,
      in vivo engraftment capacity, and sensitivity to degenerative stimuli similar to
      those of embryo-derived motor neurons. We show that the converting fibroblasts do
      not transit through a proliferative neural progenitor state, and thus form bona
      fide motor neurons via a route distinct from embryonic development. Our findings
      demonstrate that fibroblasts can be converted directly into a specific
      differentiated and functional neural subtype, the spinal motor neuron.

PMID- 21852224
TI  - FibroTest and Fibroscan performances revisited in patients with chronic hepatitis
      C. Impact of the spectrum effect and the applicability rate.
AB  - BACKGROUND: Two widely used biomarkers of fibrosis, FibroTest and liver stiffness
      measurement (LSM), have been mostly validated in patients with chronic hepatitis
      C (CHC) using the standard area under the ROC curve (sAUROC) which is not the
      most appropriate method due to the risk of fibrosis spectrum effect. Furthermore
      the performance of these biomarkers have not been assessed in "intention to
      diagnose" which takes into account the failures and non-reliable results. AIM:
      The aim was to compare the accuracy of FibroTest and LSM for the diagnosis of
      fibrosis using sAUROC, the pairwise comparison of fibrosis stages by Obuchowski
      measure (wAUROC), and these AUROCs reassessed after taking into account the
      applicability rates. METHODS: One thousand two hundred and eighty-nine patients
      with CHC and 604 healthy volunteers were analyzed. The performances of biomarkers
      assessed were compared in a patients-only group (P1: n=1289), in a population
      combining both patients and healthy volunteers (P2: n=1893) and in a simulated
      population (P3: n=1893) with the prevalence of stages observed in a reference
      population, to demonstrate the impact of spectrum effect. Applicability rates
      were estimated prospectively in 24,872 consecutive FibroTest and in 13,669
      consecutive LSM examinations. RESULTS: Using wAUROC, the conclusions of studies
      with reliable results in P1 were different than in those of P2 and in P3. There
      was a lower performance of FibroTest versus LSM in P1 (0.864 [0.855-0.873] vs.
      0.883 [0.874-0.892]; P=0.002) which was not found in P2 (0.893 [0.887-0.900] vs.
      0.894 [0.887-0.901]; P=0.86) and in P3 (0.899 [0.893-0.905] vs 0.902 [0.895
      0.909]; P=0.60). Using the sAUROC, in P1, P2 and P3, there was no significant
      difference between FibroTest and LSM performance for advanced fibrosis and a
      lower performance of FibroTest versus LSM for cirrhosis. In intention to
      diagnose, using wAUROCs performances were higher for FibroTest vs. LSM in P1
      (0.857 [0.848-0.866] vs. 0.814 [0.807-0.821]; P<0.0001) and P2 (0.885 [0.879
      0.892] vs. 0.743 [0.737-0.749]; P<0.0001), without difference in P3 (0.891 [0.885
      0.897] vs. 0.894 [0.887-0.901]; P=0.90). Using sAUROC, the significant
      differences in favor of FibroTest vs LSM persisted also for the diagnosis of
      advanced fibrosis, both in P1 and P2 (P<0.0001) and for the diagnosis of
      cirrhosis in P1 (P<0.001). CONCLUSION: When the spectrum effects and
      applicability rates were taken into account, LSM had lower performance results
      than FibroTest for the diagnosis of fibrosis stages.

PMID- 21852225
TI  - Budd-Chiari syndrome secondary to hepatocellular carcinoma.

PMID- 21852226
TI  - Solar UV doses of young Americans and vitamin D3 production.
AB  - BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation (290-315 nm) that
      affects human health in both detrimental (skin cancers) and beneficial (vitamin
      D3) ways. Serum 25-hydroxyvitamin D concentrations from young Americans (<= 19
      years) show that many have deficient (< 50 nmol/L, 20 ng/mL) or insufficient (<
      75 nmol/L, 30 ng/mL) vitamin D levels, indicating that they are not getting
      enough sun exposure. Those findings are in conflict with some calculated,
      published values that suggest people make "ample" vitamin D3 (~ 1,000 IU/day)
      from their "casual," or everyday, outdoor exposures even if they diligently use
      sunscreens with sun protection factor (SPF) 15. OBJECTIVE: We estimated how much
      vitamin D3 young Americans (n = ~ 2,000) produce from their everyday outdoor
      ultraviolet doses in the North (45 degrees N) and South (35 degrees N) each
      season of the year with and without vacationing. METHODS: For these vitamin D3
      calculations, we used geometric conversion factors that change planar to whole
      body doses, which previous calculations did not incorporate. RESULTS: Our
      estimates suggest that American children may not be getting adequate outdoor UVB
      exposures to satisfy their vitamin D3 needs all year, except some Caucasians
      during the summer if they do not diligently wear sunscreens except during beach
      vacations. CONCLUSION: These estimates suggest that most American children may
      not be going outside enough to meet their minimal (~ 600 IU/day) or optimal (>=
      1,200 IU/day) vitamin D requirements.

PMID- 21852227
TI  - Care from health visitors trained in psychological intervention methods may
      prevent depression in mothers not depressed 6 weeks postnatally.

PMID- 21852228
TI  - The p73 tumor suppressor is targeted by Pirh2 RING finger E3 ubiquitin ligase for
      the proteasome-dependent degradation.
AB  - The p73 gene, a homologue of the p53 tumor suppressor, is expressed as TA and
      DeltaN isoforms. TAp73 has similar activity as p53 and functions as a tumor
      suppressor whereas DeltaNp73 has both pro- and anti-survival functions. While p73
      is rarely mutated in spontaneous tumors, the expression status of p73 is linked
      to the sensitivity of tumor cells to chemotherapy and prognosis for many types of
      human cancer. Thus, uncovering its regulators in tumors is of great interest.
      Here, we found that Pirh2, a RING finger E3 ubiquitin ligase, promotes the
      proteasome-dependent degradation of p73. Specifically, we showed that knockdown
      of Pirh2 up-regulates, whereas ectopic expression of Pirh2 down-regulates,
      expression of endogenous and exogenous p73. In addition, Pirh2 physically
      associates with and promotes TAp73 polyubiquitination both in vivo and in vitro.
      Moreover, we found that p73 can be degraded by both 20 S and 26 S proteasomes.
      Finally, we showed that Pirh2 knockdown leads to growth suppression in a TAp73
      dependent manner. Taken together, our findings indicate that Pirh2 promotes the
      proteasomal turnover of TAp73, and thus targeting Pirh2 to restore TAp73-mediated
      growth suppression in p53-deficient tumors may be developed as a novel anti
      cancer strategy.

PMID- 21852229
TI  - Raptor and Rheb negatively regulate skeletal myogenesis through suppression of
      insulin receptor substrate 1 (IRS1).
AB  - The mammalian target of rapamycin (mTOR) is essential for skeletal myogenesis
      through controlling distinct cellular pathways. The importance of the canonical
      mTOR complex 1 signaling components, including raptor, S6K1, and Rheb, had been
      suggested in muscle maintenance, growth, and metabolism. However, the role of
      those components in myogenic differentiation is not entirely clear. In this study
      we have investigated the functions of raptor, S6K1, and Rheb in the
      differentiation of C2C12 mouse myoblasts. We find that although mTOR knockdown
      severely impairs myogenic differentiation as expected, the knockdown of raptor,
      as well as Rheb, enhances differentiation. Consistent with a negative role for
      these proteins in myogenesis, overexpression of raptor or Rheb inhibits C2C12
      differentiation. On the other hand, neither knockdown nor overexpression of S6K1
      has any effect. Moreover, the enhanced differentiation elicited by raptor or Rheb
      knockdown is accompanied by increased Akt activation, elevated IRS1 protein
      levels, and decreased Ser-307 (human Ser-312) phosphorylation on IRS1. Finally,
      IRS1 knockdown eliminated the enhancement in differentiation elicited by raptor
      or Rheb knockdown, suggesting that IRS1 is a critical mediator of the myogenic
      functions of raptor and Rheb. In conclusion, the Rheb-mTOR/raptor pathway
      negatively regulates myogenic differentiation by suppressing IRS1-PI3K-Akt
      signaling. These findings underscore the versatility of mTOR signaling in
      biological regulations and implicate the existence of novel mTOR complexes and/or
      signaling mechanism in skeletal myogenesis.

PMID- 21852230
TI  - A role for Rac3 GTPase in the regulation of autophagy.
AB  - The process of autophagy is situated at the intersection of multiple cell
      signaling pathways, including cell metabolism, growth, and death, and hence is
      subject to multiple forms of regulation. We previously reported that inhibition
      of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final
      step in the post-translational prenylation of so-called CAAX proteins, results in
      the induction of autophagy which enhances cell death in some cancer cells. In
      this study, using siRNA-mediated knockdown of a group of small GTPases that are
      predicted Icmt substrates, we identify Rac3 GTPase as a negative regulator of the
      process of autophagy. Knockdown of Rac3, but not the closely related isoforms
      Rac1 and Rac2, results in induction of autophagy. Ectopic expression of Rac3,
      significantly rescues cells from autophagy and cell death induced by Icmt
      inhibition, strengthening the notion of an isoform-specific autophagy regulatory
      function of Rac3. This role of Rac3 was observed in multiple cell lines with
      varying Rac subtype expression profiles, suggesting its broad involvement in the
      process. The identification of this less-studied Rac member as a novel regulator
      provides new insight into autophagy and opens opportunities in identifying
      additional regulatory inputs of the process.

PMID- 21852232
TI  - Protein kinase A-mediated serine 35 phosphorylation dissociates histone H1.4 from
      mitotic chromosome.
AB  - Global histone H1 phosphorylation correlates with cell cycle progression.
      However, the function of site-specific H1 variant phosphorylation remains
      unclear. Our mass spectrometry analysis revealed a novel N-terminal
      phosphorylation of the major H1 variant H1.4 at serine 35 (H1.4S35ph), which
      accumulates at mitosis immediately after H3 phosphorylation at serine 10. Protein
      kinase A (PKA) was found to be a kinase for H1.4S35. Importantly, Ser-35
      phosphorylated H1.4 dissociates from mitotic chromatin. Moreover, H1.4S35A
      substitution mutant cannot efficiently rescue the mitotic defect following H1.4
      depletion, and inhibition of PKA activity increases the mitotic chromatin
      compaction depending on H1.4. Our results not only indicate that PKA-mediated
      H1.4S35 phosphorylation dissociates H1.4 from mitotic chromatin but also suggest
      that this phosphorylation is necessary for specific mitotic functions.

PMID- 21852231
TI  - Altered arachidonate distribution in macrophages from caveolin-1 null mice
      leading to reduced eicosanoid synthesis.
AB  - In this work we have studied the effect of caveolin-1 deficiency on the
      mechanisms that regulate free arachidonic acid (AA) availability. The results
      presented here demonstrate that macrophages from caveolin-1-deficient mice
      exhibit elevated fatty acid incorporation and remodeling and a constitutively
      increased CoA-independent transacylase activity. Mass spectrometry-based
      lipidomic analyses reveal stable alterations in the profile of AA distribution
      among phospholipids, manifested by reduced levels of AA in choline
      glycerophospholipids but elevated levels in ethanolamine glycerophospholipids and
      phosphatidylinositol. Furthermore, macrophages from caveolin-1 null mice show
      decreased AA mobilization and prostaglandin E(2) and LTB(4) production upon cell
      stimulation. Collectively, these results provide insight into the role of
      caveolin-1 in AA homeostasis and suggest an important role for this protein in
      the eicosanoid biosynthetic response.

PMID- 21852233
TI  - Cellular iron depletion and the mechanisms involved in the iron-dependent
      regulation of the growth arrest and DNA damage family of genes.
AB  - Iron plays a crucial part in proliferation while iron deficiency results in
      G(1)/S arrest, DNA damage, and apoptosis. However, the precise role of iron in
      cell cycle control remains unclear. We showed that iron depletion using the iron
      chelators, desferrioxamine (DFO), or 2-hydroxy-1-napthylaldehyde isonicotinoyl
      hydrazone (311), increased the mRNA levels of the growth arrest and DNA damage
      45alpha gene, GADD45alpha (Darnell, G. and Richardson, D. R. (1999) Blood 94, 781
      792). In this study, we examined the effect of iron depletion on up-regulating
      GADD family members involved in growth control, including cell cycle arrest,
      apoptosis, and DNA repair, making them therapeutic targets for tumor suppression.
      We showed the GADD family members were up-regulated by cellular iron depletion.
      Further, up-regulation of GADD45alpha after iron deprivation was independent of
      hypoxia-inducible factor-1alpha (HIF-1alpha), octamer-1 (Oct-1), p53 and early
      growth response 1 (Egr1). We then analyzed the regulatory elements responsible
      for iron depletion-mediated regulation of GADD45alpha and identified the specific
      transcription factor/s involved. This region was within -117 bp and -81 bp
      relative to the start codon where the consensus sequences of three transcription
      factors are located: the CCAAT-binding factor/nuclear factor-Y (NF-Y), the
      stabilizing molecule v-MYB and the enhancer, CCAAT enhancer-binding protein
      (CEBPalpha). Mutation analysis, shRNA studies, Western blotting, and
      electrophoretic mobility shift assays led to the identification of NF-Y in the
      transcriptional up-regulation of GADD45alpha after iron depletion. Furthermore,
      like GADD45alpha, NF-YA was up-regulated after iron chelation and down-regulated
      by iron supplementation. These results are important for understanding the
      mechanisms of iron depletion-mediated cell cycle arrest, DNA damage repair, and
      apoptosis.

PMID- 21852234
TI  - Identification and functional and spectral characterization of a globin-coupled
      histidine kinase from Anaeromyxobacter sp. Fw109-5.
AB  - Two-component signal transduction systems regulate numerous important
      physiological functions in bacteria. In this study we have identified, cloned,
      overexpressed, and characterized a dimeric full-length heme-bound (heme:protein,
      1:1 stoichiometry) globin-coupled histidine kinase (AfGcHK) from Anaeromyxobacter
      sp. strain Fw109-5 for the first time. The Fe(III), Fe(II)-O(2), and Fe(II)-CO
      complexes of the protein displayed autophosphorylation activity, whereas the
      Fe(II) complex had no significant activity. A H99A mutant lost heme binding
      ability, suggesting that this residue is the heme proximal ligand. Moreover, His
      183 was proposed as the autophosphorylation site based on the finding that the
      H183A mutant protein was not phosphorylated. The phosphate group of
      autophosphorylated AfGcHK was transferred to Asp-52 and Asp-169 of a response
      regulator, as confirmed from site-directed mutagenesis experiments. Based on the
      amino acid sequences and crystal structures of other globin-coupled oxygen sensor
      enzymes, Tyr-45 was assumed to be the O(2) binding site at the heme distal side.
      The O(2) dissociation rate constant, 0.10 s(-1), was substantially increased up
      to 8.0 s(-1) upon Y45L mutation. The resonance Raman frequencies representing
      nu(Fe-O2) (559 cm(-1)) and nu(O-O) (1149 cm(-1)) of the Fe(II)-O(2) complex of
      Y45F mutant AfGcHK were distinct from those of the wild-type protein (nu(Fe-O2),
      557 cm(-1); nu(O-O), 1141 cm(-1)), supporting the proposal that Tyr-45 is located
      at the distal side and forms hydrogen bonds with the oxygen molecule bound to the
      Fe(II) complex. Thus, we have successfully identified and characterized a novel
      heme-based globin-coupled oxygen sensor histidine kinase, AfGcHK, in this study.

PMID- 21852235
TI  - Reciprocally regulated chromatin association of Cockayne syndrome protein B and
      p53 protein.
AB  - The Cockayne syndrome complementation group B (CSB) protein is an ATP-dependent
      chromatin remodeler with an essential function in transcription-coupled DNA
      repair, and mutations in the CSB gene are associated with Cockayne syndrome. The
      p53 tumor suppressor has been known to interact with CSB, and both proteins have
      been implicated in overlapping biological processes, such as DNA repair and
      aging. The significance of the interaction between CSB and p53 has remained
      unclear, however. Here, we show that the chromatin association of CSB and p53 is
      inversely related. Using in vitro binding and chromatin immunoprecipitation
      approaches, we demonstrate that CSB facilitates the sequence-independent
      association of p53 with chromatin when p53 concentrations are low and that this
      is achieved by the interaction of CSB with the C-terminal region of p53.
      Remarkably, p53 prevents CSB from binding to nucleosomes when p53 concentrations
      are elevated. Examining the enzymatic properties of CSB revealed that p53
      excludes CSB from nucleosomes by occluding a nucleosome interaction surface on
      CSB. Together, our results suggest that the reciprocal regulation of chromatin
      access by CSB and p53 could be part of a mechanism by which these two proteins
      coordinate their activities to regulate DNA repair, cell survival, and aging.

PMID- 21852236
TI  - Glutathione peroxidase-1 deficiency augments proinflammatory cytokine-induced
      redox signaling and human endothelial cell activation.
AB  - Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant enzyme, the deficiency
      of which promotes atherogenesis. Accordingly, we examined the mechanisms by which
      GPx-1 deficiency enhances endothelial cell activation and inflammation. In human
      microvascular endothelial cells, we found that GPx-1 deficiency augments
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) expression by redox-dependent mechanisms that involve NFkappaB.
      Suppression of GPx-1 enhanced TNF-alpha-induced ROS production and ICAM-1
      expression, whereas overexpression of GPx-1 attenuated these TNF-alpha-mediated
      responses. GPx-1 deficiency prolonged TNF-alpha-induced IkappaBalpha degradation
      and activation of ERK1/2 and JNK. JNK or NFkappaB inhibition attenuated TNF-alpha
      induction of ICAM-1 and VCAM-1 expression in GPx-1-deficient and control cells,
      whereas ERK1/2 inhibition attenuated only VCAM-1 expression. To analyze further
      signaling pathways involved in GPx-1-mediated protection from TNF-alpha-induced
      ROS, we performed microarray analysis of human microvascular endothelial cells
      treated with TNF-alpha in the presence and absence of GPx-1. Among the genes
      whose expression changed significantly, dual specificity phosphatase 4 (DUSP4),
      encoding an antagonist of MAPK signaling, was down-regulated by GPx-1
      suppression. Targeted DUSP4 knockdown enhanced TNF-alpha-mediated ERK1/2 pathway
      activation and resulted in increased adhesion molecule expression, indicating
      that GPx-1 deficiency may augment TNF-alpha-mediated events, in part, by
      regulating DUSP4.

PMID- 21852237
TI  - Histone H1 variants are differentially expressed and incorporated into chromatin
      during differentiation and reprogramming to pluripotency.
AB  - There are seven linker histone variants in human somatic cells (H1.0 to H1.5 and
      H1X), and their prevalence varies as a function of cell type and differentiation
      stage, suggesting that the different variants may have distinct roles. We have
      revisited this notion by using new methodologies to study pluripotency and
      differentiation, including the in vitro differentiation of human embryonic stem
      (ES) and teratocarcinoma cells and the reprogramming of keratinocytes to induced
      pluripotent stem cells. Our results show that pluripotent cells (PCs) have
      decreased levels of H1.0 and increased levels of H1.1, H1.3, and H1.5 compared
      with differentiated cells. PCs have a more diverse repertoire of H1 variants,
      whereas in differentiated cells, H1.0 expression represents ~80% of the H1
      transcripts. In agreement with their prevalent expression in ES cells, the
      regulatory regions of H1.3 and H1.5 genes were found to be occupied by
      pluripotency factors. Moreover, the H1.0 gene promoter contains bivalent domains
      (H3K4me2 and H3K27me3) in PCs, suggesting that this variant is likely to have an
      important role during differentiation. Indeed, the knockdown of H1.0 in human ES
      did not affect self-renewal but impaired differentiation. Accordingly, H1.0 was
      recruited to the regulatory regions of differentiation and pluripotency genes
      during differentiation, confirming that this histone variant plays a critical
      role in the regulation of these genes. Thus, histone H1 variant expression is
      controlled by a variety of mechanisms that produce distinct but consistent H1
      repertoires in pluripotent and differentiated cells that appear critical to
      maintain the functionality of such cells.

PMID- 21852238
TI  - Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL.
AB  - Parkinson disease (PD)- and cancer-associated protein, DJ-1, mediates cellular
      protection via many signaling pathways. Deletions or mutations in the DJ-1 gene
      are directly linked to autosomal recessive early-onset PD. DJ-1 has potential
      roles in mitochondria. Here, we show that DJ-1 increases its mitochondrial
      distribution in response to ultraviolet B (UVB) irradiation and binds to Bcl
      X(L). The interactions between DJ-1 and Bcl-X(L) are oxidation-dependent. DJ
      1(C106A), a mutant form of DJ-1 that is unable to be oxidized, binds Bcl-X(L)
      much less than DJ-1 does. Moreover, DJ-1 stabilizes Bcl-X(L) protein level by
      inhibiting its ubiquitination and degradation through ubiquitin proteasome system
      (UPS) in response to UVB irradiation. Furthermore, under UVB irradiation,
      knockdown of DJ-1 leads to increases of Bcl-X(L) ubiquitination and degradation
      upon UVB irradiation, thereby increasing mitochondrial Bax, caspase-3 activation
      and PARP cleavage. These data suggest that DJ-1 protects cells against UVB
      induced cell death dependent on its oxidation and its association with
      mitochondrial Bcl-X(L).

PMID- 21852239
TI  - Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein.
AB  - Alzheimer disease (AD) is associated with extracellular deposition of proteolytic
      fragments of amyloid precursor protein (APP). Although mutations in APP and
      proteases that mediate its processing are known to result in familial, early
      onset forms of AD, the mechanisms underlying the more common sporadic, yet
      genetically complex forms of the disease are still unclear. Four single
      nucleotide polymorphisms within the ubiquilin-1 gene have been shown to be
      genetically associated with AD, implicating its gene product in the pathogenesis
      of late onset AD. However, genetic linkage between ubiquilin-1 and AD has not
      been confirmed in studies examining different populations. Here we show that
      regardless of genotype, ubiquilin-1 protein levels are significantly decreased in
      late onset AD patient brains, suggesting that diminished ubiquilin function may
      be a common denominator in AD progression. Our interrogation of putative
      ubiquilin-1 activities based on sequence similarities to proteins involved in
      cellular quality control showed that ubiquilin-1 can be biochemically defined as
      a bona fide molecular chaperone and that this activity is capable of preventing
      the aggregation of amyloid precursor protein both in vitro and in live neurons.
      Furthermore, we show that reduced activity of ubiquilin-1 results in augmented
      production of pathogenic amyloid precursor protein fragments as well as increased
      neuronal death. Our results support the notion that ubiquilin-1 chaperone
      activity is necessary to regulate the production of APP and its fragments and
      that diminished ubiquilin-1 levels may contribute to AD pathogenesis.

PMID- 21852240
TI  - Cytoplasmic N-glycosyltransferase of Actinobacillus pleuropneumoniae is an
      inverting enzyme and recognizes the NX(S/T) consensus sequence.
AB  - N-Linked glycosylation is a frequent protein modification that occurs in all
      three domains of life. This process involves the transfer of a preassembled
      oligosaccharide from a lipid donor to asparagine side chains of polypeptides and
      is catalyzed by the membrane-bound oligosaccharyltransferase (OST). We
      characterized an alternative bacterial pathway wherein a cytoplasmic N
      glycosyltransferase uses nucleotide-activated monosaccharides as donors to modify
      asparagine residues of peptides and proteins. N-Glycosyltransferase is an
      inverting glycosyltransferase and recognizes the NX(S/T) consensus sequence. It
      therefore exhibits similar acceptor site specificity as eukaryotic OST, despite
      the unrelated predicted structural architecture and the apparently different
      catalytic mechanism. The identification of an enzyme that integrates some of the
      features of OST in a cytoplasmic pathway defines a novel class of N-linked
      protein glycosylation found in pathogenic bacteria.

PMID- 21852241
TI  - Structural basis of activation of bitter taste receptor T2R1 and comparison with
      Class A G-protein-coupled receptors (GPCRs).
AB  - The human bitter taste receptors (T2Rs) are non-Class A members of the G-protein
      coupled receptor (GPCR) superfamily, with very limited structural information.
      Amino acid sequence analysis reveals that most of the important motifs present in
      the transmembrane helices (TM1-TM7) of the well studied Class A GPCRs are absent
      in T2Rs, raising fundamental questions regarding the mechanisms of activation and
      how T2Rs recognize bitter ligands with diverse chemical structures. In this
      study, the bitter receptor T2R1 was used to systematically investigate the role
      of 15 transmembrane amino acids in T2Rs, including 13 highly conserved residues,
      by amino acid replacements guided by molecular modeling. Functional analysis of
      the mutants by calcium imaging analysis revealed that replacement of Asn-66(2.65)
      and the highly conserved Asn-24(1.50) resulted in greater than 90% loss of
      agonist-induced signaling. Our results show that Asn-24(1.50) plays a crucial
      role in receptor activation by mediating an hydrogen bond network connecting TM1
      TM2-TM7, whereas Asn-66(2.65) is essential for binding to the agonist
      dextromethorphan. The interhelical hydrogen bond between Asn-24(1.50) and Arg
      55(2.54) restrains T2R receptor activity because loss of this bond in I27A and
      R55A mutants results in hyperactive receptor. The conserved amino acids Leu
      197(5.50), Ser-200(5.53), and Leu-201(5.54) form a putative LXXSL motif which
      performs predominantly a structural role by stabilizing the helical conformation
      of TM5 at the cytoplasmic end. This study provides for the first time mechanistic
      insights into the roles of the conserved transmembrane residues in T2Rs and
      allows comparison of the activation mechanisms of T2Rs with the Class A GPCRs.

PMID- 21852242
TI  - Inhibitors of Src and focal adhesion kinase promote endocrine specification:
      impact on the derivation of beta-cells from human pluripotent stem cells.
AB  - Stepwise approaches for the derivation of beta-cells from human embryonic stem
      cells have been described. However, low levels of endocrine specification limit
      the final yield of insulin-producing beta-cells. In this study, we show that the
      pyrrolo-pyrimidine Src family kinase (SFK) inhibitor PP2 effectively promotes the
      endocrine specification of human embryonic stem cell derivatives based on its
      capacity to induce the expression of proendocrine transcription factors (NGN3,
      NEUROD1, NKX2.2, and PAX4) and to significantly increase the final yield of
      insulin-positive cells. We further demonstrate that PP2 inhibits the activation
      of focal adhesion kinase (FAK), and selective inhibition of this kinase is also
      sufficient to induce early endocrine commitment based on increased expression of
      NGN3, NEUROD1, and NKX2.2. Additional studies using dominant negative constructs
      and isolated human fetal pancreata suggest that c-Src is at least partially
      responsible for inhibiting early endocrine specification. Mechanistically, we
      propose that inhibition of SFK/FAK signaling can promote endocrine specification
      by limiting activation of the TGFbetaR/Smad2/3 pathway. Moreover, we show that
      inhibition of SFK/FAK signaling suppresses cell growth, increases the expression
      of the beta-cell-associated cyclin-dependent kinase inhibitor p57kip2, and
      simultaneously suppresses the expression of Id1 and Id2. This study has important
      implications for the derivation of beta-cells for the cell-based therapy of
      diabetes and sheds new light on the signaling events that regulate early
      endocrine specification.

PMID- 21852244
TI  - Structure and evolutionary history of DISC1.
AB  - Evolutionary and protein structural analyses can provide functional insights into
      genes implicated in human psychiatric diseases. Even eukaryotic organisms lacking
      nervous systems contain homologues of many key signalling molecules of animal
      neurons implying that human cognition derives, in part, from modifications of
      ancestral molecules and complexes. One protein whose evolutionary origin is
      obscure is DISC1 (disrupted in schizophrenia 1) whose gene locus has been
      associated with many psychiatric conditions including schizophrenia, clinical
      depression and bipolar disorder. This protein's rapid evolution and its unusual
      amino acid and alpha-helix composition have hindered searches for DISC1
      homologues in species other than vertebrates. Here, we review the evolution and
      structure of the DISC1 protein in the light of in-depth sequence analyses. These
      predict DISC1 orthologues in diverse eukaryotic organisms, including early
      branching animals such as amphioxus, sea anemone, amoebas and Trichoplax, and in
      plants and algae. DISC1 thus is widespread among eukaryotes, although it remains
      absent from fungi, nematodes and Diptera, including fruit flies. These
      observations now permit studies of DISC1 function in simple non-vertebrate model
      organisms. Surprisingly, these analyses also identify between two and four
      sequence repeats in DISC1 orthologues. The first two of these repeats show
      significant sequence similarity to the UVR family of globular domains. These UVR
      like repeats are predicted to contain, not coiled coil structures, but rather two
      closely associated antiparallel alpha-helices. One common missense variant in
      DISC1 (L607F) lies within the second DISC1 UVR-like domain. These observations
      should assist in delineating the functional regions of the DISC1 protein.

PMID- 21852243
TI  - Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in
      African Americans.
AB  - Genome-wide association studies (GWAS) have revealed 19 common genetic variants
      that are associated with breast cancer risk. Testing of the index signals found
      through GWAS and fine-mapping of each locus in diverse populations will be
      necessary for characterizing the role of these risk regions in contributing to
      inherited susceptibility. In this large study of breast cancer in African
      American women (3016 cases and 2745 controls), we tested the 19 known risk
      variants identified by GWAS and replicated associations (P < 0.05) with only 4
      variants. Through fine-mapping, we identified markers in four regions that better
      capture the association with breast cancer risk in African Americans as defined
      by the index signal (2q35, 5q11, 10q26 and 19p13). We also identified
      statistically significant associations with markers in four separate regions
      (8q24, 10q22, 11q13 and 16q12) that are independent of the index signals and may
      represent putative novel risk variants. In aggregate, the more informative
      markers found in the study enhance the association of these risk regions with
      breast cancer in African Americans [per allele odds ratio (OR) = 1.18, P = 2.8 *
      10(-24) versus OR = 1.04, P = 6.1 * 10(-5)]. In this detailed analysis of the
      known breast cancer risk loci, we have validated and improved upon markers of
      risk that better characterize their association with breast cancer in women of
      African ancestry.

PMID- 21852246
TI  - Additional genomic duplications in AZFc underlie the b2/b3 deletion-associated
      risk of spermatogenic impairment in Han Chinese population.
AB  - The azoospermia factor c (AZFc) region on the Y chromosome is a genetically
      dynamic locus in the human genome. Numerous genomic rearrangements, including
      deletion, duplication and inversion, have been identified in AZFc. The complete
      deletion of AZFc can cause spermatogenic impairment. However, the roles of
      partial AZFc deletions (e.g. b2/b3 deletion) in spermatogenesis are controversial
      and variable among human populations. Secondary duplication has been hypothesized
      to be a compensatory factor for partial AZFc deletions. To further study genomic
      duplications in AZFc as a potential genetic modifier underlying the phenotypic
      variations of partial AZFc deletions in spermatogenesis, we conducted
      comprehensive molecular analyses in 711 idiopathic infertile men and 390 healthy
      controls. Unexpectedly, we found that additional AZFc duplications accompanying
      the b2/b3 deletion, instead of the b2/b3 deletion alone, led to the b2/b3
      deletion-associated risk of spermatogenic impairment previously reported in Han
      Chinese population. In addition, partial AZFc duplication also rendered a risk
      factor in the non-deletion patients. DAZ is a multi-copy AZFc gene (DAZ1-DAZ4)
      implicated in spermatogenesis. Genetic variations do exist between DAZ copies.
      Intriguingly, we found that the DAZ1/2 cluster was the main duplicated copies in
      the partial AZFc duplications associated with spermatogenic impairment,
      suggesting a potential different role of spermatogenesis between DAZ copies. Our
      findings demonstrated that additional AZFc duplications did not compensate but
      convey the susceptibility of the b2/b3 deletion to spermatogenic impairment in
      the tested population. Notably, genomic duplications and deletions in AZFc
      deserve comprehensive investigations to uncover spermatogenic roles of the AZFc
      region.

PMID- 21852247
TI  - Adeno-associated virus-mediated expression of beta-hexosaminidase prevents
      neuronal loss in the Sandhoff mouse brain.
AB  - Sandhoff disease, a GM2 gangliosidosis caused by a deficiency in beta
      hexosaminidase, is characterized by progressive neurodegeneration. Although loss
      of neurons in association with lysosomal storage of glycosphingolipids occurs in
      patients with this disease, the molecular pathways that lead to the accompanying
      neurological defects are unclear. Using an authentic murine model of GM2
      gangliosidosis, we examined the pattern of neuronal loss in the central nervous
      system and investigated the effects of gene transfer using recombinant adeno
      associated viral vectors expressing beta-hexosaminidase subunits (rAAV2/1-Hex).
      In 4-month-old Sandhoff mice with neurological deficits, cells staining
      positively for the apoptotic signature in the TUNEL reaction were found in the
      ventroposterior medial and ventroposterior lateral (VPM/VPL) nuclei of the
      thalamus. There was progressive loss of neuronal density in this region with age.
      Comparable loss of neuronal density was identified in the lateral vestibular
      nucleus of the brainstem and a small but statistically significant loss was
      present in the ventral spinal cord. Loss of neurons was not detected in other
      regions that were analysed. Administration of rAAV2/1-Hex into the brain of
      Sandhoff mice prevented the decline in neuronal density in the VPM/VPL.
      Preservation of neurons in the VPM/VPL was variable at the humane endpoint in
      treated animals, but correlated directly with increased lifespan. Loss of neurons
      was localized to only a few regions in the Sandhoff brain and was prevented by
      rAAV-mediated transfer of beta-hexosaminidase gene function at considerable
      distances from the site of vector administration.

PMID- 21852245
TI  - Exploring the genomic basis of pharmacoresistance in epilepsy: an integrative
      analysis of large-scale gene expression profiling studies on brain tissue from
      epilepsy surgery.
AB  - Some patients with pharmacoresistant epilepsy undergo therapeutic resection of
      the epileptic focus. At least 12 large-scale microarray studies on brain tissue
      from epilepsy surgery have been published over the last 10 years, but they have
      failed to make a significant impact upon our understanding of pharmacoresistance,
      because (1) doubts have been raised about their reproducibility, (2) only a small
      number of the gene expression changes found in each microarray study have been
      independently validated and (3) the results of different studies have not been
      integrated to give a coherent picture of the genetic changes involved in epilepsy
      pharmacoresistance. To overcome these limitations, we (1) assessed the
      reproducibility of the microarray studies by calculating the overlap between
      lists of differentially regulated genes from pairs of microarray studies and
      determining if this was greater than would be expected by chance alone, (2) used
      an inter-study cross-validation technique to simultaneously verify the expression
      changes of large numbers of genes and (3) used the combined results of the
      different microarray studies to perform an integrative analysis based on enriched
      gene ontology terms, networks and pathways. Using this approach, we respectively
      (1) demonstrate that there are statistically significant overlaps between the
      gene expression changes in different publications, (2) verify the differential
      expression of 233 genes and (3) identify the biological processes, networks and
      genes likely to be most important in the development of pharmacoresistant
      epilepsy. Our analysis provides novel biologically plausible candidate genes and
      pathways which warrant further investigation to assess their causal relevance.

PMID- 21852248
TI  - Mitochondrial DNA disease: new options for prevention.
AB  - Very recently, two papers have presented intriguing data suggesting that
      prevention of transmission of human mitochondrial DNA (mtDNA) disease is
      possible. [Craven, L., Tuppen, H.A., Greggains, G.D., Harbottle, S.J., Murphy,
      J.L., Cree, L.M., Murdoch, A.P., Chinnery, P.F., Taylor, R.W., Lightowlers, R.N.
      et al. (2010) Pronuclear transfer in human embryos to prevent transmission of
      mitochondrial DNA disease. Nature, 465, 82-85. Tachibana, M., Sparman, M.,
      Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., Li, Y., Ramsey, C.,
      Kolotushkina, O. and Mitalipov, S. (2009) Mitochondrial gene replacement in
      primate offspring and embryonic stem cells. Nature, 461, 367-372.] These recent
      advances raise hopes for families with mtDNA disease; however, the successful
      translational of these techniques to clinical practice will require further
      research to test for safety and to maximize efficacy. Furthermore, in the UK,
      amendment to the current legislation will be required. Here, we discuss the
      clinical and scientific background, studies we believe are important to establish
      safety and efficacy of the techniques and some of the potential concerns about
      the use of these approaches.

PMID- 21852250
TI  - Global transcriptome analysis of constitutive resistance to the white pine weevil
      in spruce.
AB  - Constitutive defense mechanisms are critical to the understanding of defense
      mechanisms in conifers because they constitute the first barrier to attacks by
      insect pests. In interior spruce, trees that are putatively resistant and
      susceptible to attacks by white pine weevil (Pissodes strobi) typically exhibit
      constitutive differences in traits such as resin duct size and number, bark
      thickness, and terpene content. To improve our knowledge of their genetic basis,
      we compared globally the constitutive expression levels of 17,825 genes between
      20 putatively resistant and 20 putatively susceptible interior spruce trees from
      the British Columbia tree improvement program. We identified 54 upregulated and
      137 downregulated genes in resistant phenotypes, relative to susceptible
      phenotypes, with a maximum fold change of 2.24 and 3.91, respectively. We found a
      puzzling increase of resistance by downregulated genes, as one would think that
      "procuring armaments" is the best defense. Also, although terpenes and phenolic
      compounds play an important role in conifer defense, we found few of these genes
      to be differentially expressed. We found 15 putative small heat-shock proteins
      (sHSP) and several other stress-related proteins to be downregulated in resistant
      trees. Downregulated putative sHSP belong to several sHSP classes and represented
      58% of all tested putative sHSP. These proteins are well known to be involved in
      plant response to various kinds of abiotic stress; however, their role in
      constitutive resistance is not yet understood. The lack of correspondence between
      transcriptome profile clusters and phenotype classifications suggests that weevil
      resistance in spruce is a complex trait.

PMID- 21852251
TI  - Post-marketing surveillance (PMS) of all patients treated with irinotecan in
      Japan: clinical experience and ADR profile of 13,935 patients.
AB  - OBJECTIVE: The actual condition of drug utilization and the adverse drug
      reactions profile of irinotecan hydrochloride hydrate (irinotecan), an antitumor
      drug, were examined on the basis of all the case survey results from April 1995
      to January 2000. METHODS: Drug utilization and the adverse drug reactions profile
      of irinotecan were figured out by checking of the patient conditions at the start
      of therapy and monitoring during on-therapy period in this survey. RESULTS: Among
      the 13 935 patients investigated, 32% had non-small cell lung cancer, 16% had
      colorectal cancer, 15% had ovarian cancer and 14% had small cell lung cancer, all
      principal cancers in which irinotecan was domestically approved for use. Most
      frequent regimens of each cancer were concomitant use with cisplatin for non
      small cell lung cancer and small cell lung cancer (38 and 46%, respectively),
      concomitant use with cisplatin or mitomycin for ovarian cancer (each 30%) and
      irinotecan alone for colorectal cancer (51%). The major (grade 3 or more) adverse
      drug reactions were myelosuppressions such as leukopenia (23.8 and 38.3% for lone
      and concomitant use, respectively) thrombocytopenia (6.5 and 14.3%) and
      gastrointestinal tract disorders such as diarrhea (10.2 and 10.0%). CONCLUSIONS:
      It was reconfirmed that the incidences of serious leukopenia, thrombocytopenia
      and diarrhea were high among the patients with contraindication or careful
      administration of its use prescribed in the drug package insert. Therefore, for
      proper use of irinotecan, it is important to discriminate the patient on the
      basis of risk status.

PMID- 21852249
TI  - Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast
      cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer
      Association Consortium.
AB  - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms
      (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The
      initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)
      positive tumors. Using data from the Breast Cancer Association Consortium (BCAC),
      we sought to determine whether risks differ by ER, progesterone receptor (PR),
      human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size,
      and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two
      highly correlated SNPs rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1),
      for up to 46 036 invasive breast cancer cases and 46 930 controls from 39
      studies. Analyses by tumor characteristics focused on subjects reporting to be
      white women of European ancestry and were based on 25 458 cases, of which 87% had
      ER data. The SNP at 1p11.2 showed significantly stronger associations with ER
      positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95%
      CI = 1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98-1.07, case
      only P-heterogeneity = 7.6 * 10(-5)]. The association with ER-positive tumors was
      stronger for tumors of lower grade (case-only P= 6.7 * 10(-3)) and lobular
      histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most
      tumor subtypes evaluated, including triple-negative breast cancers, which has not
      been described previously. Our results underscore the need for large pooling
      efforts with tumor pathology data to help refine risk estimates for SNP
      associations with susceptibility to different subtypes of breast cancer.

PMID- 21852253
TI  - Association study of BAK1 gene polymorphisms in Spanish rheumatoid arthritis and
      systemic lupus erythematosus cohorts.

PMID- 21852252
TI  - A 40-month multicentre, randomised placebo-controlled study to assess the
      efficacy and carry-over effect of repeated intra-articular injections of
      hyaluronic acid in knee osteoarthritis: the AMELIA project.
AB  - OBJECTIVE: AMELIA (OsteoArthritis Modifying Effects of Long-term Intra-articular
      Adant) was designed to compare against placebo the efficacy and safety of
      repeated injections of hyaluronic acid (HA) and its effect on disease progression
      over 40 months. METHODS: A multicentre, randomised, patient and evaluator
      blinded, controlled study in 306 patients fulfilling American College of
      Rheumatology criteria for knee osteoarthritis, radiological grades II-III
      (Kellgren-Lawrence) and joint space width >= 2 mm. Patients received four cycles
      of five intra-articular HA or placebo injections with a follow-up of 6 months
      after the first and second cycles, and 1 year after the third and fourth cycles.
      Osteoarthritis Research Society International (OARSI) 2004 responder criteria
      were used to assess efficacy. The consumption of rescue medication was a
      secondary outcome. Adverse events were recorded for safety purposes. RESULTS: At
      the 40-month visit significantly more patients responded to HA compared with
      placebo (OARSI 2004, p=0.004). The number of responders to HA increased through
      the study, whereas those to placebo did not change. Significant differences were
      also found in favour of HA for each individual component of the OARSI 2004. No
      safety problems were recorded. CONCLUSIONS: The results of AMELIA offer pioneer
      evidence that repeated cycles of intra-articular injections of HA not only
      improve knee osteoarthritis symptoms during the in-between cycle period but also
      exert a marked carry-over effect for at least 1 year after the last cycle. In
      this respect, it is not possible to establish if this carry-over effect reflects
      true osteoarthritis remission or just a modification of the disease's natural
      course. ClinicalTrials.gov number, NCT00669032.

PMID- 21852254
TI  - Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan:
      interim analysis of 3881 patients.
AB  - OBJECTIVE: An interim analysis of an all-patient postmarketing surveillance
      programme in Japan to investigate the safety of tocilizumab for the treatment of
      rheumatoid arthritis (RA) in the real world. METHODS: This analysis included 3881
      patients. Patients received 8 mg/kg of tocilizumab every 4 weeks, and were
      observed for 28 weeks. Data on baseline characteristics and adverse events (AE)
      were collected. RESULTS: Total and serious AE were reported as 167 and 27
      events/100 patient-years, respectively. The most frequent AE and serious AE were
      infections. Logistic regression analysis identified the following risk factors
      for the development of serious infection: concurrent or medical history of
      respiratory disorders; prednisolone dose at baseline >=5 mg/day; and age >=65
      years. Twenty-five patients died, and the standardised mortality ratio, with the
      Japanese general population in 2008 as reference, was 1.66, similar to the
      results from the Japanese cohort study for RA patients. CONCLUSIONS: Tocilizumab
      is acceptably safe in the real clinical setting. Tocilizumab needs to be used
      with consideration of the benefit-risk balance to avoid serious infections in
      elderly patients and those on high doses of corticosteroids or with a concurrent
      or medical history of respiratory disorders.

PMID- 21852255
TI  - Outcomes following the surgical ligation of the patent ductus arteriosus in
      premature infants in Scotland.
AB  - OBJECTIVE: To determine morbidity, mortality and associated risk factors
      following patent ductus arteriosus (PDA) ligation in premature infants. METHODS:
      Retrospective case note audit of premature infants referred to a national
      paediatric cardiothoracic surgical service (2001-2007) with univariate and
      multivariate analysis of potential risk factors for mortality and morbidity.
      RESULTS: 125 infants were enrolled (median gestational age 26 weeks (IQR 25-27
      weeks), median birth weight 840 g (IQR 730-1035 g)). Referral characteristics
      were median LA:Ao 1.8 (IQR 1.5-2.0), 80% ventilated, 18.4% continuous positive
      airway pressure, 70% diuretics and 58% prior treatment with cyclooxygenase
      inhibitors (COIs). Median age at PDA ligation was 31 days (IQR 25-41 days).
      Postoperative characteristics were median time to extubation 5 days (IQR 3-10
      days), 36.0% corticosteroids, 46.8% domiciliary oxygen and 4.8% vocal cord palsy.
      The 30-day and 1-year mortality rates were 4.8% and 12.8%, respectively, with
      neurodisability in 32% of survivors. All deaths occurred in the ventilated group
      and were mainly attributable to bronchopulmonary dysplasia (BPD). Gestation and
      fractional inspired oxygen (FiO(2))>60% were significantly associated with 30-day
      mortality. FiO(2), ventilation, lack of prior COIs and postoperative
      corticosteroids were significantly associated with 1-year mortality. Preoperative
      FiO(2)>40% and lack of prior COIs retained independent significance for death at
      1 year. CONCLUSIONS: PDA ligation is well tolerated, with evidence of early
      benefit. The incidence of neurodisability or death from BPD at 1 year remains
      high. Increasing preoperative FiO(2) and lack of prior treatment with COIs are
      associated with increased mortality at 1 year.

PMID- 21852258
TI  - Inhibiting ice recrystallization and optimization of cell viability after
      cryopreservation.
AB  - The ice recrystallization inhibition activity of various mono- and disaccharides
      has been correlated with their ability to cryopreserve human cell lines at
      various concentrations. Cell viabilities after cryopreservation were compared
      with control experiments where cells were cryopreserved with dimethylsulfoxide
      (DMSO). The most potent inhibitors of ice recrystallization were 220 mM solutions
      of disaccharides; however, the best cell viability was obtained when a 200 mM d
      galactose solution was utilized. This solution was minimally cytotoxic at
      physiological temperature and effectively preserved cells during freeze-thaw. In
      fact, this carbohydrate was just as effective as a 5% DMSO solution. Further
      studies indicated that the cryoprotective benefit of d-galactose was a result of
      its internalization and its ability to mitigate osmotic stress, prevent
      intracellular ice formation and/or inhibit ice recrystallization. This study
      supports the hypothesis that the ability of a cryoprotectant to inhibit ice
      recrystallization is an important property to enhance cell viability post-freeze
      thaw. This cryoprotective benefit is observed in three different human cell
      lines. Furthermore, we demonstrated that the ability of a potential
      cryoprotectant to inhibit ice recrystallation may be used as a predictor of its
      ability to preserve cells at subzero temperatures.

PMID- 21852259
TI  - Oral contraceptives as ovarian cancer prevention.

PMID- 21852260
TI  - Ovarian cancer, five-year stage-specific relative survival rates (2004-2008).

PMID- 21852261
TI  - Ovarian cancer treatments on the horizon.

PMID- 21852262
TI  - CA-125: a biomarker put to the test.

PMID- 21852263
TI  - Ovarian cancer genome sequencing unveils findings.

PMID- 21852265
TI  - Screening for colorectal cancer--which strategy is the best?

PMID- 21852264
TI  - Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the
      Italian Randomized Controlled Trial--SCORE.
AB  - BACKGROUND: A single flexible sigmoidoscopy at around the age of 60 years has
      been proposed as an effective strategy for colorectal cancer (CRC) screening.
      METHODS: We conducted a randomized controlled trial to evaluate the effect of
      flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire
      to assess the eligibility and interest in screening was mailed to 236,568 men and
      women, aged 55-64 years, who were randomly selected from six trial centers in
      Italy. Of the 56,532 respondents, interested and eligible subjects were randomly
      assigned to the intervention group (invitation for flexible sigmoidoscopy; n =
      17,148) or the control group (no further contact; n = 17,144), between June 14,
      1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects.
      Intention-to-treat and per-protocol analyses were performed to compare the CRC
      incidence and mortality rates in the intervention and control groups. Per
      protocol analysis was adjusted for noncompliance. RESULTS: A total of 34,272
      subjects (17,136 in each group) were included in the follow-up analysis. The
      median follow-up period was 10.5 years for incidence and 11.4 years for
      mortality; 251 subjects were diagnosed with CRC in the intervention group and 306
      in the control group. Overall incidence rates in the intervention and control
      groups were 144.11 and 176.43, respectively, per 100,000 person-years. CRC
      related death was noted in 65 subjects in the intervention group and 83 subjects
      in the control group. Mortality rates in the intervention and control groups were
      34.66 and 44.45, respectively, per 100,000 person-years. In the intention-to
      treat analysis, the rate of CRC incidence was statistically significantly reduced
      in the intervention group by 18% (rate ratio [RR] = 0.82, 95% confidence interval
      [CI] = 0.69 to 0.96), and the mortality rate was non-statistically significantly
      reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control
      group. In the per-protocol analysis, both CRC incidence and mortality rates were
      statistically significantly reduced among the screened subjects; CRC incidence
      was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced
      by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group.
      CONCLUSION: A single flexible sigmoidoscopy screening between ages 55 and 64
      years was associated with a substantial reduction of CRC incidence and mortality.

PMID- 21852266
TI  - Intramuscular cavernous hemangioma in the left soleus muscle: successful surgical
      treatment.
AB  - We describe here the case of a 16-year-old boy successfully treated at our
      hospital for intramuscular cavernous hemangioma in the left soleus muscle. The
      patient was diagnosed using magnetic resonance imaging and open biopsy after
      attempted/failed surgery at another institution. We performed lower leg
      phlebography in order to identify all the feeding and draining veins of the
      cavernous hemangioma. Our surgical approach of ligation of the feeding and
      draining veins of the intramuscular cavernous hemangioma with subsequent
      thrombosis of the hemangioma proved successful, resulting in cure with no
      operative or postoperative complications, a minimal hospital stay and a good
      functional and cosmetic outcome.

PMID- 21852267
TI  - Endovascular aortic repair for spontaneous rupture of a non-aneurysmal infrarenal
      aorta.
AB  - We report the case of a patient who underwent an endovascular aortic repair for
      spontaneous rupture of a non-aneurysmal infrarenal aorta. A 67-year-old male with
      a diagnosis of infrarenal aortic rupture was referred to our hospital.
      Preoperative computed tomography showed focal ulcers adjacent to the site of
      rupture, with no evidence of aneurysm formation, suggesting that this aortic
      rupture was likely to be associated with perforation of penetrating atheromatous
      ulceration. Open surgical repair might have carried a high-risk because of the
      patient's history of laparotomy and respiratory impairment, so endovascular
      aortic repair was planned. We deployed a Powerlink proximal infrarenal cuff 25-25
      75L at the rupture site through the femoral artery, with the additional placement
      of two extra large Palmaz stents at the proximal and distal sites of the
      Powerlink stent-graft. Completion angiography showed total exclusion with no
      endoleaks. The patient was successfully extubated on the third postoperative day
      and recovered well until he contracted aspiration pneumonia two weeks after
      surgery. Unfortunately, he eventually died of a non-aortic cause three months
      after the operation. Endovascular aortic repair may be an alternative to
      conventional surgical repair for high-risk patients with spontaneous infrarenal
      aortic rupture.

PMID- 21852268
TI  - Impact of the learning curve in the use of a novel electronic chest drainage
      system after pulmonary lobectomy: a case-matched analysis on the duration of
      chest tube usage.
AB  - The objective of this investigation was to verify the impact of the learning
      curve involved after the introduction of a novel electronic chest drainage device
      on the duration of chest tube usage following pulmonary lobectomy. Propensity
      score case-matched analysis was used to compare the first consecutive 51
      lobectomy patients managed with an electronic chest drainage (E) device with 51
      controls managed with a traditional device (T). There was no difference in the
      characteristics of the two matched groups. Compared with patients managed with a
      traditional device, those with the electronic one had 1.9-day shorter duration of
      chest tube drainage (2.5 vs. 4.4 days; P<0.0001) and a 1.5-day shorter hospital
      stay (4.5 vs. 6 days; P=0.0003). Consequently, they had an average reduction in
      hospital costs of ?751 (?1802 vs. ?2553; P=0.0002). Compared with those in group
      T, patients in group E had a consistently shorter duration of chest tube use in
      relation to the very first patients treated. The learning curve sloped down for
      the first 40 patients before reaching a plateau, when the maximum benefit of
      using the electronic device was evident. Compared with traditional devices, the
      use of a novel electronic chest drainage system was beneficial from its initial
      application. The inherent learning curve was short and did not affect the
      efficiency of the system.

PMID- 21852269
TI  - Anti-endothelial cell antibodies are associated with peripheral arterial disease
      and markers of endothelial dysfunction and inflammation.
AB  - Our aim is to describe the effect of circulating anti-endothelial cell antibodies
      on the endothelial dysfunction, inflammation and early structural changes of the
      vascular wall that surround peripheral arterial disease. For this purpose, an
      observational translational controlled study was carried out. We included 32
      patients with symptomatic peripheral arterial disease and 16 healthy control
      individuals with no previous autoimmune disease. We assessed the flow-mediated
      arterial dilatation as a marker of endothelial function, the carotid intima-media
      thickness and the plasma levels of C-reactive protein in all the subjects.
      Circulating anti-endothelial cell antibodies were detected with indirect
      immunofluorescence. We found a higher prevalence of these autoantibodies in
      patients than in controls (40% vs. 6%; P=0.01). Flow-mediated arterial dilatation
      was lower in subjects with anti-endothelial cell antibodies [3.10% (0-5.05%) vs.
      12.54% (6.74-18.40%); P<0.01]. Carotid intima-media thickness [1.04 (0.78-1.17)
      vs. 0.72 (0.54-1.02) mm; P=0.01] and C-reactive protein level [10.00 (3.50-14.80)
      vs. 3.00 (3.00-6.95) mg/l; P=0.01] were higher in subjects seropositive for these
      autoantibodies. We concluded that circulating anti-endothelial cell antibodies
      could be associated with peripheral arterial disease in individuals with no
      previous autoimmune disease; however, further prospective studies are required to
      establish a causal relationship.

PMID- 21852271
TI  - Age, cumulative trauma and stressful life events, and post-traumatic stress
      symptoms among older adults in prison: do subjective impressions matter?
AB  - BACKGROUND: The aging prison population in the United States presents a
      significant public health challenge with high rates of trauma and mental health
      issues that the correctional system alone is ill-prepared to address. The purpose
      of this study was to examine the relationship of age, objective, and subjective
      measures of trauma and stressful life events and post-traumatic stress symptoms
      among older adults in prison. METHODS: Data were gathered from 334 prisoners
      (aged 55+) housed in the New Jersey Department of Corrections, as of September
      2010. An anonymous self-report, self-administered survey was mailed to the total
      population of 1,000 prisoners aged 55 years and older. Objective and subjective
      trauma was measured using the Life Stressors Checklist-Revised (LSC-R), and post
      traumatic stress symptoms were measured using the Civilian Version of the Post
      traumatic Stress Scale. FINDINGS: Results of a path analysis revealed that past
      year subjective impressions of traumatic and stressful life events had a positive
      and significant relationship to current post-traumatic stress symptoms. Age was
      found to have a significant and inverse relationship to subjective traumatic and
      stressful life events. That is, younger participants reported higher levels of
      cumulative traumatic and stressful life events and past year subjective ratings
      of being bothered by these past events. IMPLICATIONS: These findings have
      significance for interdisciplinary/interprofessional practice and appropriate
      institutional and community care, including reentry planning of older adults in
      the criminal justice system.

PMID- 21852270
TI  - Cell transformation assays for prediction of carcinogenic potential: state of the
      science and future research needs.
AB  - Cell transformation assays (CTAs) have long been proposed as in vitro methods for
      the identification of potential chemical carcinogens. Despite showing good
      correlation with rodent bioassay data, concerns over the subjective nature of
      using morphological criteria for identifying transformed cells and a lack of
      understanding of the mechanistic basis of the assays has limited their acceptance
      for regulatory purposes. However, recent drivers to find alternative
      carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU
      Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently
      ongoing to improve the objectivity of the assays, reveal the underlying molecular
      changes leading to transformation and explore the use of novel cell types. The UK
      NC3Rs held an international workshop in November 2010 to review the current state
      of the art in this field and provide directions for future research. This paper
      outlines the key points highlighted at this meeting.

PMID- 21852272
TI  - The path to quit: how awareness of a large-scale mass-media smoking cessation
      campaign promotes quit attempts.
AB  - INTRODUCTION: Although awareness of mass-media smoking cessation campaigns is
      hypothesized to affect quit behavior through changes in cessation-related
      attitudes, intentions, and motivation (cognitions), this has yet to be formally
      tested. METHODS: Structural equation modeling was used to examine whether changes
      in cessation-related cognitions mediate the relationship between awareness of a
      national mass-media smoking cessation campaign, the EX campaign, and quit
      attempts in a cohort of 3,571 current smokers drawn from eight U.S. Designated
      Market Areas and followed over an approximate six-month period. Models were
      examined in the total sample and within racial/ethnic, gender, age, and
      educational strata. RESULTS: Data suggest that there are both a direct effect of
      confirmed awareness of EX on quit attempts as well as an indirect effect mediated
      by positive changes in cessation-related cognitions. Results are not uniform
      across subgroups; stratified analyses reveal that awareness of EX is
      significantly associated with positive changes in cessation-related cognitions
      and quit attempts only in Blacks, males, and those with less than a high-school
      education. CONCLUSIONS: Those developing health communication mass-media
      campaigns need to consider how media messages might differentially impact U.S.
      subpopulations in order to elicit desired behavioral change across target
      subgroups.

PMID- 21852273
TI  - The German 2011 epidemic of Shiga toxin-producing E. Coli--the nephrological
      view.

PMID- 21852274
TI  - Comparison between bortezomib and rituximab in the treatment of antibody-mediated
      renal allograft rejection.
AB  - BACKGROUND: Antibody-mediated rejection (ABMR) following kidney transplantation
      is associated with poor allograft survival. Conventional treatment based on
      plasmapheresis (PPH) and the administration of intravenous immunoglobulins (IVIG)
      is not satisfactory. Two compounds, more specifically targeting B cells and
      plasma cells, may help to improve the prognosis: rituximab, a B-cell-depleting
      monoclonal antibody, and bortezomib, a proteasome inhibitor causing apoptosis of
      plasma cells. METHODS: Starting in February 2009, we treated 10 consecutive
      patients with ABMR according to current Banff criteria with one cycle of
      bortezomib [1.3 mg/m(2) intravenously (i.v.), Day 1, 4, 8, 11]. This group was
      compared to a historical control group of patients (n = 9) treated with a fixed
      single dose of rituximab (500 mg i.v.). All patients received PPH (6*) and IVIG
      (30 g). Patients with acute ABMR additionally received methylprednisolone (3 *
      500 mg i.v.). RESULTS: Patient survival in both groups was 100%. At 18 months
      after treatment, graft survival was 6/10 in the bortezomib group as compared to
      1/9 functioning grafts in the rituximab group (P = 0.071). Renal function was
      superior in patients treated with bortezomib as compared to rituximab-treated
      patients (serum creatinine at 9 months: 2.5 +/- 0.6 versus 5.1 +/- 2.1 mg/dL, P =
      0.008). Proteinuria was not different between both groups (9 months: 1.3 +/- 1.0
      versus 1.6 +/- 1.6 g/day, P = n.s.). CONCLUSIONS: Treatment of ABMR with
      bortezomib in addition to standard therapy was partially effective, whereas
      treatment with a fixed dose of rituximab in addition to standard therapy with PPH
      and IVIG did not result in sufficient long-term graft survival. In the future,
      new strategies including the combination of both substances and the application
      of higher doses must be discussed.

PMID- 21852276
TI  - Centennial olive trees as a reservoir of genetic diversity.
AB  - BACKGROUND AND AIMS: Genetic characterization and phylogenetic analysis of the
      oldest trees could be a powerful tool both for germplasm collection and for
      understanding the earliest origins of clonally propagated fruit crops. The olive
      tree (Olea europaea L.) is a suitable model to study the origin of cultivars due
      to its long lifespan, resulting in the existence of both centennial and
      millennial trees across the Mediterranean Basin. METHODS: The genetic identity
      and diversity as well as the phylogenetic relationships among the oldest wild and
      cultivated olives of southern Spain were evaluated by analysing simple sequence
      repeat markers. Samples from both the canopy and the roots of each tree were
      analysed to distinguish which trees were self-rooted and which were grafted. The
      ancient olives were also put into chronological order to infer the antiquity of
      traditional olive cultivars. KEY RESULTS: Only 9.6 % out of 104 a priori
      cultivated ancient genotypes matched current olive cultivars. The percentage of
      unidentified genotypes was higher among the oldest olives, which could be because
      they belong to ancient unknown cultivars or because of possible intra-cultivar
      variability. Comparing the observed patterns of genetic variation made it
      possible to distinguish which trees were grafted onto putative wild olives.
      CONCLUSIONS: This study of ancient olives has been fruitful both for germplasm
      collection and for enlarging our knowledge about olive domestication. The
      findings suggest that grafting pre-existing wild olives with olive cultivars was
      linked to the beginnings of olive growing. Additionally, the low number of
      genotypes identified in current cultivars points out that the ancient olives from
      southern Spain constitute a priceless reservoir of genetic diversity.

PMID- 21852275
TI  - Plant sexual reproduction during climate change: gene function in natura studied
      by ecological and evolutionary systems biology.
AB  - BACKGROUND: It is essential to understand and predict the effects of changing
      environments on plants. This review focuses on the sexual reproduction of plants,
      as previous studies have suggested that this trait is particularly vulnerable to
      climate change, and because a number of ecologically and evolutionarily relevant
      genes have been identified. SCOPE: It is proposed that studying gene functions in
      naturally fluctuating conditions, or gene functions in natura, is important to
      predict responses to changing environments. First, we discuss flowering time, an
      extensively studied example of phenotypic plasticity. The quantitative approaches
      of ecological and evolutionary systems biology have been used to analyse the
      expression of a key flowering gene, FLC, of Arabidopsis halleri in naturally
      fluctuating environments. Modelling showed that FLC acts as a quantitative tracer
      of the temperature over the preceding 6 weeks. The predictions of this model were
      verified experimentally, confirming its applicability to future climate changes.
      Second, the evolution of self-compatibility as exemplifying an evolutionary
      response is discussed. Evolutionary genomic and functional analyses have
      indicated that A. thaliana became self-compatible via a loss-of-function mutation
      in the male specificity gene, SCR/SP11. Self-compatibility evolved during glacial
      interglacial cycles, suggesting its association with mate limitation during
      migration. Although the evolution of self-compatibility may confer short-term
      advantages, it is predicted to increase the risk of extinction in the long term
      because loss-of-function mutations are virtually irreversible. CONCLUSIONS:
      Recent studies of FLC and SCR have identified gene functions in natura that are
      unlikely to be found in laboratory experiments. The significance of epigenetic
      changes and the study of non-model species with next-generation DNA sequencers is
      also discussed.

PMID- 21852277
TI  - No evidence of carbon limitation with tree age and height in Nothofagus pumilio
      under Mediterranean and temperate climate conditions.
AB  - BACKGROUND AND AIMS: Trees universally decrease their growth with age. Most
      explanations for this trend so far support the hypothesis that carbon (C) gain
      becomes limited with age; though very few studies have directly assessed the
      relative reductions of C gain and C demand with tree age. It has also been
      suggested that drought enhances the effect of C gain limitation in trees. Here
      tests were carried out to determine whether C gain limitation is causing the
      growth decay with tree age, and whether drought accentuates its effect. METHODS:
      The balance between C gain and C demand across tree age and height ranges was
      estimated. For this, the concentration of non-structural carbohydrates (NSCs) in
      stems and roots of trees of different ages and heights was measured in the
      deciduous temperate species Nothofagus pumilio. An ontogenetic decrease in NSCs
      indicates support for C limitation. Furthermore, the importance of drought in
      altering the C balance with ontogeny was assessed by sampling the same species in
      Mediterranean and humid climate locations in the southern Andes of Chile. Wood
      density (WD) and stable carbon isotope ratios (delta(13)C) were also determined
      to examine drought constraints on C gain. KEY RESULTS: At both locations, it was
      effectively found that tree growth ultimately decreased with tree age and height.
      It was found, however, that NSC concentrations did not decrease with tree age or
      height when WD was considered, suggesting that C limitation is not the ultimate
      mechanism causing the age/height-related declining tree growth. delta(13)C
      decreased with tree age/height at the Mediterranean site only; drought effect
      increased with tree age/height, but this pattern was not mirrored by the levels
      of NSCs. CONCLUSIONS: The results indicate that concentrations of C storage in N.
      pumilio trees do not decrease with tree age or height, and that reduced C
      assimilation due to summer drought does not alter this pattern.

PMID- 21852278
TI  - The need to re-investigate the nature of homoplastic characters: an ontogenetic
      case study of the 'bracteoles' in Atripliceae (Chenopodiaceae).
AB  - BACKGROUND AND AIMS: Within Chenopodioideae, Atripliceae have been distinguished
      by two bracteoles enveloping the female flowers/fruits, whereas in other tribes
      flowers are described as ebracteolate with persistent perianth. Molecular
      phylogenetic hypotheses suggest 'bracteoles' to be homoplastic. The origin of the
      bracteoles was explained by successive inflorescence reductions. Flower reduction
      was used to explain sex determination. Therefore, floral ontogeny was studied to
      evaluate the nature of the bracteoles and sex determination in Atripliceae.
      METHODS: Inflorescences of species of Atriplex, Chenopodium, Dysphania and
      Spinacia oleracea were investigated using light microscopy and scanning electron
      microscopy. KEY RESULTS: The main axis of the inflorescence is indeterminate with
      elementary dichasia as lateral units. Flowers develop centripetally, with first
      the formation of a perianth primordium either from a ring primordium or from five
      individual tepal primordia fusing post-genitally. Subsequently, five stamen
      primordia originate, followed by the formation of an annular ovary primordium
      surrounding a central single ovule. Flowers are either initially hermaphroditic
      remaining bisexual and/or becoming functionally unisexual at later stages, or
      initially unisexual. In the studied species of Atriplex, female flowers are
      strictly female, except in A. hortensis. In Spinacia, female and male flowers are
      unisexual at all developmental stages. Female flowers of Atriplex and Spinacia
      are protected by two accrescent fused tepal lobes, whereas the other perianth
      members are absent. CONCLUSIONS: In Atriplex and Spinacia modified structures
      around female flowers are not bracteoles, but two opposite accrescent tepal
      lobes, parts of a perianth persistent on the fruit. Flowers can achieve sexuality
      through many different combinations; they are initially hermaphroditic,
      subsequently developing into bisexual or functionally unisexual flowers, with the
      exception of Spinacia and strictly female flowers in Atriplex, which are
      unisexual from the earliest developmental stages. There may be a relationship
      between the formation of an annular perianth primordium and flexibility in floral
      sex determination.

PMID- 21852279
TI  - Current understanding and challenges in bioprocessing of stem cell-based
      therapies for regenerative medicine.
AB  - BACKGROUND: A novel manufacturing industry is emerging to translate unique
      cellular therapy bioprocesses to robust, scaled manufacturing production for
      successful clinical translation. SOURCE OF DATA: This review summarizes key
      translational issues, and current and future perspectives to improve translation
      of cell-based therapy bioprocessing, based on literature search and author
      research. AREAS OF AGREEMENT: It is widely recognized that cell-based therapies
      could revolutionize health care for a range of diseases, and that there are gaps
      in the overarching framework and technologies to generate clinical success. AREAS
      OF CONTROVERSY: There is limited understanding of how to fulfil requirements as
      regulatory and manufacturing guidelines are incomplete and few have achieved
      commercialization. GROWING POINTS: Recent developments are encouraging adoption
      of automation and quality engineering approaches for bioprocessing of cell-based
      therapies. AREAS TIMELY FOR DEVELOPING RESEARCH: Include technology development
      to improve the cost and purity of manufacture and final product quality.

PMID- 21852281
TI  - Six-month walking program changes cognitive and ADL performance in patients with
      Alzheimer.
AB  - Motor inactivity is typical in the later stages of Alzheimer's disease although
      there is evidence that physical exercise can reduce depression and enhance
      performance of daily activities. The aim of this study was to determine whether a
      walking program could reduce the functional and cognitive decline of elderly
      nursing home residents in the later stages of Alzheimer's disease. A total of 21
      patients (84 +/- 5 years) were randomly assigned to a walking program (WG) or to
      a control group (CG). A 6-minute walking test (6WT), the Barthel index of
      activities of daily living (ADLs), and Mini-Mental State Examination (MMSE) tests
      were performed before and after 24 weeks of the program. The WG showed
      significant improvement in the 6WT (20%) and ADLs (23%), while the CG decreased
      in MMSE (-47%), the WG had a slower decline (-13%). This study indicates that it
      is possible to stabilize the progressive cognitive dysfunctions in nursing home
      residents with Alzheimer's disease through a specific walking program.

PMID- 21852282
TI  - Will the interplay between genetic markers for risk factors for a disease and the
      disease itself bring genetics closer to clinical practice? Great expectations.

PMID- 21852280
TI  - Topical capsaicin for pain management: therapeutic potential and mechanisms of
      action of the new high-concentration capsaicin 8% patch.
AB  - Topical capsaicin formulations are used for pain management. Safety and modest
      efficacy of low-concentration capsaicin formulations, which require repeated
      daily self-administration, are supported by meta-analyses of numerous studies. A
      high-concentration capsaicin 8% patch (QutenzaTM) was recently approved in the EU
      and USA. A single 60-min application in patients with neuropathic pain produced
      effective pain relief for up to 12 weeks. Advantages of the high-concentration
      capsaicin patch include longer duration of effect, patient compliance, and low
      risk for systemic effects or drug-drug interactions. The mechanism of action of
      topical capsaicin has been ascribed to depletion of substance P. However,
      experimental and clinical studies show that depletion of substance P from
      nociceptors is only a correlate of capsaicin treatment and has little, if any,
      causative role in pain relief. Rather, topical capsaicin acts in the skin to
      attenuate cutaneous hypersensitivity and reduce pain by a process best described
      as 'defunctionalization' of nociceptor fibres. Defunctionalization is due to a
      number of effects that include temporary loss of membrane potential, inability to
      transport neurotrophic factors leading to altered phenotype, and reversible
      retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic
      hypersensitivity is mediated by diverse mechanisms, including altered expression
      of the capsaicin receptor TRPV1 or other key ion channels in affected or intact
      adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and
      collateral sprouting, all of which are defunctionalized by topical capsaicin.
      Evidence suggests that the utility of topical capsaicin may extend beyond painful
      peripheral neuropathies.

PMID- 21852283
TI  - Increases in muscle strength and balance using a resistance training program
      administered via a telecommunications system in older adults.
AB  - BACKGROUND: Resistance training programs have been found to improve muscle
      strength, physical function, and depressive symptoms in middle-aged and older
      adults. These programs have typically been provided in clinical facilities,
      health clubs, and senior centers, which may be inconvenient and/or cost
      prohibitive for some older adults. The purpose of this study was to investigate
      the effectiveness of an automated telemedicine intervention that provides real
      time guidance and monitoring of resistance training in the home. METHODS: A
      randomized clinical trial in 103 middle-aged or older participants. Participants
      were assigned to use of a theory-driven interactive voice response system
      designed to promote resistance training (Telephone-Linked Computer-based Long
      term Interactive Fitness Trainer; n = 52) or to an attention control (n = 51) for
      a period of 12 months. Measurements of muscle strength, balance, walk distance,
      and mood were obtained at baseline, 3, 6, and 12 months. RESULTS: We observed
      increased strength, improved balance, and fewer depressive symptoms in the
      intervention group than in the control group. Using generalized estimating
      equations modeling, group differences were statistically significant for knee
      flexion strength (p = .035), single-leg stance time (p = .029), and Beck
      Depression Inventory (p = .030). CONCLUSIONS: This computer-based
      telecommunications exercise intervention led to improvements in participants'
      strength, balance, and depressive symptoms. Because of their low cost and easy
      accessibility, computer-based interventions may be a cost-effective way of
      promoting exercise in the home.

PMID- 21852284
TI  - Parental longevity and diabetes risk in the Diabetes Prevention Program.
AB  - BACKGROUND: Longevity clusters in families, and parental longevity may be
      associated with lower risk of chronic diseases in their children. It is unknown
      if diabetes risk is associated with parental longevity. METHODS: We evaluated
      participants in the Diabetes Prevention Program with a parental history
      questionnaire at study entry. We classified them into five groups: premature
      death (parental death at age < 50 years), parental longevity (living to at least
      80 years), and three intermediate groups (alive by age 49 but dying at age 50-59,
      60-69, or 70-79). Those with alive parents and younger than 80 years were
      excluded. We analyzed separately effects of paternal (n = 2,165) and maternal (n
      = 1,739) longevity on diabetes incidence and risk after an average follow-up of
      3.2 years. RESULTS: At baseline, more diabetes risk factors (parental history of
      diabetes, coronary heart disease, higher body mass index, homeostasis model
      assessment for insulin resistance, and corrected insulin response) were found in
      participants whose parents died prematurely. Diabetes incidence was 9.5 cases/100
      person-years in the 229 whose fathers died prematurely. In the 618 with paternal
      longevity, the rate was 6.6 cases/100 person-years (hazard ratio [95% confidence
      interval] = 0.68 [0.49-0.94]). The rates were 10.7 cases/100 person-years (n =
      156) and 7.3 cases/100 person-years (n = 699, hazard ratio = 0.67 [95% confidence
      interval 0.47-0.95]) for those with maternal premature death or longevity,
      respectively. Associations with demographic and diabetes risk factors had minimal
      influence on the reduced risk found in those with paternal (adjusted hazard ratio
      = 0.78, 95% confidence interval 0.52-1.16) and maternal (adjusted hazard ratio =
      0.64, 95% confidence interval 0.41-1.01) longevity. CONCLUSION: Parental
      longevity is associated with lower diabetes incidence in adults at high risk of
      type 2 diabetes.

PMID- 21852285
TI  - Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare, progressive segmental
      premature aging disease that includes scleroderma-like skin, progressive joint
      contracture, and atherosclerosis. Affected individuals die prematurely of heart
      attacks or strokes. Extracellular matrix dysregulation is implicated as a factor
      in disease progression. We analyzed messenger RNA and protein levels for matrix
      metalloproteinases (MMPs)-2,-3, and -9 in HGPS primary human dermal fibroblasts
      using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and
      gelatin zymography. MMP-3 messenger RNA and protein levels decreased
      significantly with increasing donor age in HGPS fibroblasts but not in controls.
      MMP-2 messenger RNA also showed a donor age-dependent decrease in HGPS
      fibroblasts, but levels of secreted protein were unchanged. MMP-9 was similar in
      HGPS and control cultures. The decreased MMP-3 may represent a shift in the
      inherent extracellular matrix-degrading proteolytic balance in favor of matrix
      deposition in HGPS. This metalloproteinase has the potential to serve as a
      biomarker of therapeutic efficacy when assessing treatments for HGPS.

PMID- 21852286
TI  - The relationship between intervening hospitalizations and transitions between
      frailty states.
AB  - BACKGROUND: Frailty among older persons is a dynamic process, characterized by
      frequent transitions between frailty states over time. We performed a prospective
      longitudinal study to evaluate the relationship between intervening
      hospitalizations and these transitions. METHODS: We studied 754 nondisabled
      community-living persons, aged 70 years or older. Frailty, assessed every 18
      months for 108 months, was defined on the basis of muscle weakness, exhaustion,
      low physical activity, shrinking, and slow walking speed. Participants were
      classified as frail if they met three or more of these criteria, prefrail if they
      met one or two of the criteria, or nonfrail if they met none of the criteria.
      Hospitalizations were ascertained every month for a median of 108 months.
      RESULTS: The exposure rates (95% confidence interval) of hospitalization per
      1,000 months, based on frailty status at the start of each 18-month interval,
      were 19.7 (16.2-24.0) nonfrail, 32.9 (29.8-36.2) prefrail, and 57.2 (52.9-63.1)
      frail. The likelihood of transitioning from states of greater frailty to lesser
      frailty (ie, recovering) was consistently lower based on exposure to intervening
      hospitalizations, with adjusted hazard ratios per each hospitalization ranging
      from 0.46 (95% confidence interval: 0.21-1.03) for the transition from frail to
      nonfrail states to 0.52 (95% confidence interval: 0.42-0.65) for the transition
      from prefrail to nonfrail states. Hospitalization had more modest and less
      consistent effects on transitions from states of lesser frailty to greater
      frailty. Nonetheless, transitions from nonfrail to frail states were uncommon in
      the absence of a hospitalization. CONCLUSIONS: Recovery from prefrail and frail
      states is substantially diminished by intervening hospitalizations. These results
      provide additional evidence highlighting the adverse consequences of
      hospitalization in older persons.

PMID- 21852287
TI  - Dissemination of the rmtB gene carried on IncF and IncN plasmids among
      Enterobacteriaceae in a pig farm and its environment.
AB  - OBJECTIVES: To investigate the prevalence and characterization of 16S rRNA
      methylase-producing bacteria in a pig farm and its environment in East China.
      METHODS: Enterobacteriaceae isolates and metagenomic DNA from 102 pig faecal
      samples from a pig farm and 97 soil samples taken in or around the farm were
      screened for the presence of 16S rRNA methylase genes. The clonal relationships
      of 16S rRNA methylase-positive isolates, plasmid content and other associated
      resistance genes were also characterized. RESULTS: Fifty-six rmtB-positive
      Enterobacteriaceae isolates, including 54 Escherichia coli, 1 Morganella morganii
      and 1 Proteus mirabilis, were recovered from 55 pig faecal samples. Nineteen rmtB
      positive bacteria, including 13 E. coli, 2 M. morganii, 2 Leclercia
      adecarboxylata, 1 Enterobacter aerogenes and 1 Enterobacter cloacae, were
      recovered from 16 soil samples. Among the 75 rmtB-positive isolates, 31 and 25
      also carried the qepA and bla(CTX-M) genes, respectively. The qepA gene co
      localized with rmtB on the F2:A-:B1 plasmids and the bla(CTX-M-65) gene co
      localized with rmtB on the F33:A-:B- plasmids. The rmtB gene was also found to be
      associated with the IncN plasmids. Clonal transmission of rmtB-positive E. coli
      isolates was observed between different pig groups and soil samples. CONCLUSIONS:
      Both horizontal gene transfer and clonal spread could be responsible for the
      dissemination of the rmtB gene in the pig farm and its environment. To our
      knowledge, this study is the first report of rmtB-positive bacteria from farmland
      soils and indicates that these antibiotic-resistant bacteria and/or resistance
      genes could be acquired by humans through the food chain.

PMID- 21852288
TI  - Comparative analysis of numerical and experimental data of orthodontic mini
      implants.
AB  - The purpose of this study was to compare numerical simulation data derived from
      finite element analysis (FEA) to experimental data on mini-implant loading. Nine
      finite element (FE) models of mini-implants and surrounding bone were derived
      from corresponding experimental specimens. The animal bone in the experiment
      consisted of bovine rib. The experimental groups were based on implant type,
      length, diameter, and angle of insertion. One experimental specimen was randomly
      selected from each group and was digitized in a microCT scanner. The FE models
      consisted of bone pieces containing Aarhus mini-implants with dimensions 1.5 * 7
      mm and 1.5 * 9 mm or LOMAS mini-implants (dimensions 1.5 * 7 mm, 1.5 * 9 mm, and
      2 * 7 mm). Mini-implants were inserted in two different ways, perpendicular to
      the bone surface or at 45 degrees to the direction of the applied load. Loading
      and boundary conditions in the FE models were adjusted to match the experimental
      situation, with the force applied on the neck of the mini-implants, along the
      mesio-distal direction up to a maximum of 0.5 N. Displacement and rotation of
      mini-implants after force application calculated by FEA were compared to
      previously recorded experimental deflections of the same mini-implants. Analysis
      of data with the Altman-Bland test and the Youden plot demonstrated good
      agreement between numerical and experimental findings (P = not significant) for
      the models selected. This study provides further evidence of the appropriateness
      of the FEA as an investigational tool in relevant research.

PMID- 21852289
TI  - Comorbidity and the limitations of volume and focus as organizing principles.
AB  - Some scholars advocate for health care organizations designed around the
      principles of volume and focus, while others suggest that the complexity of
      patient care renders this approach to organizing care inefficient (and
      ineffective). This article attempts to reconcile these views, drawing on the idea
      of organizational capabilities as knowledge integration to motivate an empirical
      examination of the extent to which the efficiency benefits of hospital volume and
      focus depend on the degree of patient comorbidity. In doing so, the article has
      two aims: (a) to shed light on both the benefits and limitations of volume and
      focus as organizing principles and (b) to contribute to our understanding of the
      implications of comorbidity for the organization of health care delivery. Using
      data on U.S. hospitals, the author finds evidence that the efficiency benefits of
      volume and focus are diminishing in the level of patient comorbidity.

PMID- 21852290
TI  - Trends in care for uninsured adults and disparities in care by insurance status.
AB  - The uninsured fare worse than the insured on various measures, yet there is
      little evidence regarding trends in care for the uninsured and disparities by
      insurance status. Given changes in the health care system and the safety net,
      disparities between insured and uninsured populations may be changing over time.
      This article considers trends in access, chronic disease control, and heart
      attack care by insurance status and the disparity in these measures between
      uninsured and insured nonelderly adults, controlling for demographic
      characteristics to account for potential changes in the composition of these
      populations. Rates for the uninsured for all outcomes have generally been stable
      from the mid-1990s to mid-2000s, with fluctuation in some measures over shorter
      periods. In addition, there is a persistent disparity between the privately
      insured and uninsured on access measures. The gap between the uninsured and
      insured has not narrowed, though disparities generally have not worsened either.

PMID- 21852291
TI  - Commentary: Preparing internists for the 21st century: a response to the recent
      RAND survey of internal medicine education.

PMID- 21852292
TI  - Can a patient-centered medical home lead to better patient outcomes? The quality
      implications of Geisinger's ProvenHealth Navigator.
AB  - One of the primary goals of the patient-centered medical home (PCMH) is to
      provide higher quality care that leads to better patient outcomes. Currently,
      there is only limited evidence regarding the ability of PCMHs to achieve this
      goal. This article demonstrates the effect of PCMHs in improving certain clinical
      outcomes, as shown by the ProvenHealth Navigator (PHN), an advanced PCMH model
      developed and implemented by Geisinger Health System. In this study, the authors
      examined the claims data from Geisinger Health Plan between 2005 and 2009 and
      estimated the effect of PHN on reducing amputation rates among patients with
      diabetes, end-stage renal disease, myocardial infarction, and stroke. The results
      show that, despite its relatively short period of existence, PHN has led to
      significant improvements in certain outcomes, further illustrating its potential
      as a care delivery model to be adopted on a wider scale.

PMID- 21852293
TI  - Predictive factors of pathologically proven noninvasive tumor characteristics in
      T1aN0M0 peripheral non-small cell lung cancer.
AB  - BACKGROUND: We retrospectively analyzed preoperative factors that may predict
      pathologically invasive tumor characteristics, including lymph node involvement,
      and pleural and vessel invasion in patients with cT1aN0M0 peripheral non-small
      cell lung cancer (NSCLC), in an attempt to identify candidates for pulmonary
      resection less than lobectomy. METHODS: We reviewed the charts of 363 patients in
      whom cT1aN0M0 lung cancer in the lung periphery had been diagnosed or was
      suspected, based on high-resolution CT scan of 1- or 2-mm-slice intervals, within
      1 month of surgical resection, and examined the relationships between
      preoperative clinical information and pathologic invasive tumor characteristics,
      corresponding to lymph node involvement and pleural and vessel invasion. RESULTS:
      Multivariate analysis showed that a tumor disappearance ratio (TDR) < 0.5, the
      presence of spiculation, and an absence of air bronchograms were statistically
      significant independent predictors of pathologic invasiveness. Most TDR >= 0.5
      tumors were noninvasive (98.7%), and only one patient had a recurrence within 5
      years after surgical resection. Of the tumors with a TDR >= 0.5 without
      spiculation, 98.3% were noninvasive, and all those patients remained recurrence
      free for 5 years after surgery. CONCLUSION: The combination of a TDR >= 0.5 and
      the absence of spiculation was highly predictive of noninvasive or minimally
      invasive NSCLC. Future studies should evaluate whether limited resection of these
      tumors provides acceptable outcomes.

PMID- 21852294
TI  - Selective serotonin reuptake inhibitors and pulmonary arterial hypertension: a
      case-control study.
AB  - BACKGROUND: Animal and human studies suggest that selective serotonin reuptake
      inhibitors (SSRIs) might be useful for the prevention or treatment of pulmonary
      arterial hypertension. METHODS: We conducted a population-based, nested case
      control study to explore the hypothesis that SSRIs might reduce the risk of
      pulmonary arterial hypertension. Cases were individuals who developed pulmonary
      arterial hypertension requiring pharmacologic treatment. For each case, we
      selected up to 10 matched control subjects. Exposure to SSRIs and non-SSRI
      antidepressants was ascertained using administrative data. The outcome of
      pulmonary arterial hypertension requiring pharmacologic therapy was defined as
      the receipt of a drug specific for the treatment of pulmonary arterial
      hypertension. RESULTS: In contrast to our hypothesis, and likely because of
      residual confounding, we found a positive association between SSRI use and
      pulmonary arterial hypertension (adjusted OR, 1.55; 95% CI, 1.13-2.13).
      CONCLUSIONS: At conventional doses, SSRIs are not associated with a reduced risk
      of pulmonary arterial hypertension.

PMID- 21852295
TI  - Diagnostic accuracy of single-photon emission tomography ventilation/perfusion
      lung scan in the diagnosis of pulmonary embolism.
AB  - BACKGROUND: Planar ventilation/perfusion (V/Q) lung scintigraphy is a validated
      tool for the diagnosis of pulmonary embolism (PE). Nevertheless, given the high
      rate of nonconclusive V/Q, further investigation is often necessary. V/Q single
      photon emission CT (SPECT) scan could improve V/Q performance, but sparse data
      are available on its accuracy. This study assessed the diagnostic performance of
      V/Q SPECT scan in a cohort of consecutive patients with suspected PE. METHODS:
      Three hundred twenty-one consecutive patients with a clinical suspicion of PE
      were prospectively included. Patients suspected of having PE were managed
      according to a reference diagnostic strategy validated by a 3-month follow-up. In
      addition to the reference strategy, patients had a V/Q SPECT scan, the results of
      which were compared with the initial work-up results. RESULTS: Prevalence of PE
      was 0 of 41 (0%; 95% CI, 0%-9%), six of 134 (4%; 95% CI, 2%-9%),15 of 36 (42%;
      95% CI, 27%-58%), and 28 of 32 (88%; 95% CI, 72%-95%) in the normal,
      low,intermediate, and high V/Q SPECT scan probability groups, respectively. The
      combination of V/Q SPECT scan with clinical probability was diagnostic in 88% of
      patients. CONCLUSIONS: V/Q SPECT scan results show satisfactory accuracy for PE
      diagnosis. Validation of dedicated interpretation criteria is required, followed
      by outcome studies that use V/Q SPECT scan as part of a diagnostic strategy to
      rule out PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01183026; URL:
      www.clinicaltrials.gov

PMID- 21852296
TI  - A strategy combining imaging and laboratory biomarkers in comparison with a
      simplified clinical score for risk stratification of patients with acute
      pulmonary embolism.
AB  - BACKGROUND: This study aimed to assess the performance of two prognostic models
      the European Society of Cardiology (ESC) model and the simplified Pulmonary
      Embolism Severity Index (sPESI)-in predicting short-term mortality in patients
      with pulmonary embolism (PE). METHODS: We compared the test characteristics of
      the ESC model and the sPESI for predicting 30-day outcomes in a cohort of 526
      patients with objectively confirmed PE. The primary end point of the study was
      all-cause mortality. The secondary end point included all-cause mortality,
      nonfatal symptomatic recurrent VTE, or nonfatal major bleeding. RESULTS: Overall,
      40 of 526 patients died (7.6%; 95% CI, 5.3%-9.9%) during the first month of
      follow-up. The sPESI classified fewer patients as low risk (31% [165 of 526], 95%
      CI, 27%-35%) compared with the ESC model (39% [207 of 526], 95% CI, 35% to 44%; P
      < .01). Importantly however, low-risk patients based on the sPESI had no 30-day
      mortality compared with 3.4% (95% CI, 0.9-5.8) in low-risk patients by the ESC
      model. The secondary end point occurred in 1.8% of patients in the sPESI low-risk
      and 5.8% in the ESC low-risk group (difference, 4.0 percentage points; 95% CI,
      0.2-7.8). The prognostic ability of the ESC model remained significant in the
      subgroup of patients at high-risk according to the sPESI model (OR 1.95, 95% CI,
      1.41 to 2.71, P < .001). CONCLUSIONS: Both the sPESI and the ESC model
      successfully predict 30-day mortality after acute symptomatic PE, but exclusion
      of an adverse early outcome does not appear to require routine imaging procedures
      or laboratory biomarker testing.

PMID- 21852297
TI  - Nationwide trends of severe sepsis in the 21st century (2000-2007).
AB  - BACKGROUND: Severe sepsis is common and often fatal. The expanding armamentarium
      of evidence-based therapies has improved the outcomes of persons with this
      disease. However, the existing national estimates of the frequency and outcomes
      of severe sepsis were made before many of the recent therapeutic advances.
      Therefore, it is important to study the outcomes of this disease in an aging US
      population with rising comorbidities. METHODS: We used the Healthcare Costs and
      Utilization Project's Nationwide Inpatient Sample (NIS) to estimate the frequency
      and outcomes of severe sepsis hospitalizations between 2000 and 2007. We
      identified hospitalizations for severe sepsis using International Classification
      of Diseases, Ninth Revision, Clinical Modification codes indicating the presence
      of sepsis and organ system failure. Using weights from NIS, we estimated the
      number of hospitalizations for severe sepsis in each year. We combined these with
      census data to determine the number of severe sepsis hospitalizations per 100,000
      persons. We used discharge status to identify in-hospital mortality and compared
      mortality rates in 2000 with those in 2007 after adjusting for demographics,
      number of organ systems failing, and presence of comorbid conditions. RESULTS:
      The number of severe sepsis hospitalizations per 100,000 persons increased from
      143 in 2000 to 343 in 2007. The mean number of organ system failures during
      admission increased from 1.6 to 1.9 (P < .001). The mean length of hospital stay
      decreased from 17.3 to 14.9 days. The mortality rate decreased from 39% to 27%.
      However, more admissions ended with discharge to a long-term care facility in
      2007 than in 2000 (35% vs 27%, P < .001). CONCLUSIONS: An increasing number of
      admissions for severe sepsis combined with declining mortality rates contribute
      to more individuals surviving to hospital discharge. Importantly, this leads to
      more survivors being discharged to skilled nursing facilities and home with in
      home care. Increased attention to this phenomenon is warranted.

PMID- 21852298
TI  - Decline of resting inspiratory capacity in COPD: the impact on breathing pattern,
      dyspnea, and ventilatory capacity during exercise.
AB  - BACKGROUND: To better understand the interrelationships among disease severity,
      inspiratory capacity (IC), breathing pattern, and dyspnea, we studied responses
      to symptom-limited cycle exercise in a large cohort with COPD. METHODS: Analysis
      was conducted on data from two previously published replicate clinical trials in
      427 hyperinflated patients with COPD. Patients were divided into disease severity
      quartiles based on FEV(1) % predicted. Spirometry, plethysmographic lung volumes,
      and physiologic and perceptual responses to constant work rate (CWR) cycle
      exercise at 75% of the peak incremental work rate were compared. RESULTS: Age,
      body size, and COPD duration were similar across quartiles. As the FEV(1)
      quartile worsened (mean, 62%, 49%, 39%, and 27% predicted), functional residual
      capacity increased (144%, 151%, 164%, and 185% predicted), IC decreased (86%,
      81%, 69%, and 60% predicted), and peak incremental cycle work rate decreased
      (66%, 55%, 50%, and 44% predicted); CWR endurance time was 9.7, 9.3, 8.2, and 7.3
      min, respectively. During CWR exercise, as FEV(1) quartile worsened, peak minute
      ventilation ($$?dot{?mathrm{V}}$$e) and tidal volume (Vt) decreased, whereas an
      inflection or plateau of the Vt response occurred at a progressively lower
      $$?dot{?mathrm{V}}$$e (P < .0005), similar percentage of peak
      $$?dot{?mathrm{V}}$$e (82%-86%), and similar Vt/IC ratio (73%-77%). Dyspnea
      intensity at this inflection point was also similar across quartiles (3.1-3.7
      Borg units) but accelerated steeply to intolerable levels thereafter. CONCLUSION:
      Progressive reduction of the resting IC with increasing disease severity was
      associated with the appearance of critical constraints on Vt expansion and a
      sharp increase in dyspnea to intolerable levels at a progressively lower
      ventilation during exercise.

PMID- 21852299
TI  - Changes in macrophage inhibitory factor correlate with changes in bone mineral
      density in glucocorticoid-treated patients with rheumatoid arthritis.
AB  - OBJECTIVES: To investigate whether changes in bone density and turnover are
      associated with changes in inflammatory mediators in RA patients treated with
      glucocorticoids (GCs) upon vitamin D treatment in comparison with alendronate
      treatment. METHODS: RA patients (n = 40) on long-term oral GC treatment received
      either alfacalcidol or alendronate. At baseline and after 18 months, we measured
      cytokines capable of antagonizing GCs [macrophage migration inhibitory factor
      (MIF), IL-13 and IL-7], cytokines causing T-cell differentiation (IL-6, IL-7, IL
      12, IL-10 and IL-23) and cytokines produced by effector T cells (IFN-gamma, IL-4,
      IL-17, IL-22). Associations of cytokine profiles with bone markers and BMD
      changes of the lumbar spine were explored using multiple regression analyses that
      corrected for study medication and risk factors of osteoporosis (gender, age,
      cumulative/change in GC dose). RESULTS: Alendronate, unlike alfacalcidol,
      increased BMD changes in the lumbar spine. Most cytokines were below detection
      limits. MIF and IL-23 were detectable in almost all samples; neither alfacalcidol
      nor alendronate significantly influenced serum concentrations of these cytokines.
      Interestingly, changes in MIF correlated positively with changes in BMD of the
      lumber spine (Pearson's correlation = 0.31), and in multivariate analysis
      adjusting for treatment, age and change in GC dose (P = 0.022). CONCLUSION:
      During GC treatment, changes in the GC-antagonist MIF were positively correlated
      with changes in BMD, which could mean MIF has bone-protecting capacities in
      patients suffering from GC-induced bone destruction. Further studies need to
      validate the importance of these findings.

PMID- 21852300
TI  - Looking at paediatric rheumatology over the past 50 years.

PMID- 21852301
TI  - Complex Medicare advantage choices may overwhelm seniors--especially those with
      impaired decision making.
AB  - The proliferation of Medicare Advantage plans has given Medicare enrollees more
      choices, but these could be overwhelming for some, especially for those with
      impaired decision-making capabilities. We analyzed national survey data and
      linked Medicare enrollment data for the period 2004-07 to examine the effects on
      enrollment of expanded choices and benefits in the Medicare Advantage program.
      The availability of more plan options was associated with increased enrollment in
      Medicare Advantage when elderly Medicare beneficiaries chose from a limited
      number of plans-for example, fewer than fifteen plans. Enrollment was unchanged
      or decreased in Medicare Advantage when beneficiaries chose from larger numbers
      of plans-for example, fifteen to thirty, or more than thirty. Elderly adults with
      low cognitive function were less responsive to the generosity of available
      benefits than those with high cognitive function when choosing between
      traditional Medicare and Medicare Advantage. Simplifying choices in Medicare
      Advantage could improve beneficiaries' enrollment decisions, strengthen value
      based competition among plans, and extend the benefits of choice to seniors with
      impaired cognition. It could also lower their out-of-pocket costs.

PMID- 21852302
TI  - Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth
      cohort.
AB  - BACKGROUND: Little is known about the aetiology of chronic fatigue
      syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role
      for premorbid mood disorder. AIMS: To examine childhood and early adult
      adversity, ill health and physical activity as premorbid risk markers for CFS/ME
      by 42 years, taking psychopathology into account. METHOD: Data were from the 1958
      British birth cohort, a prospective study from birth to 42 years (n = 11 419).
      The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS
      like illness (n = 241) at 42 years. RESULTS: Adjusting for psychopathology,
      parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16-3.81), childhood
      gastrointestinal symptoms (OR = 1.58, 95% CI 1.00-2.50) and parental reports of
      many colds (OR = 1.65, 95% CI 1.09-2.50) were independently associated with self
      reported CFS/ME. Female gender and premorbid psychopathology were the only risk
      markers for CFS-like illness, independent of comorbid psychopathology.
      CONCLUSIONS: This confirms the importance of premorbid psychopathology in the
      aetiological pathways of CFS/ME, and replicates retrospective findings that
      childhood adversity may play a role in a minority.

PMID- 21852303
TI  - Love, eye contact and the developmental origins of empathy v. psychopathy.
AB  - BACKGROUND: A propensity to attend to other people's emotions is a necessary
      condition for human empathy. AIMS: To test our hypothesis that psychopathic
      disorder begins as a failure to attend to the eyes of attachment figures, using a
      'love' scenario in young children. METHOD: Children with oppositional defiant
      disorder, assessed for callous-unemotional traits, and a control group were
      observed in a love interaction with mothers. Eye contact and affection were
      measured for each dyad. RESULTS: There was no group difference in affection and
      eye contact expressed by the mothers. Compared with controls, children with
      oppositional defiant disorder expressed lower levels of affection back towards
      their mothers; those with high levels of callous-unemotional traits showed
      significantly lower levels of affection than the children lacking these traits.
      As predicted, the former group showed low levels of eye contact toward their
      mothers. Low eye contact was not correlated with maternal coercive parenting or
      feelings toward the child, but was correlated with psychopathic fearlessness in
      their fathers. CONCLUSIONS: Impairments in eye contact are characteristic of
      children with callous-unemotional traits, and these impairments are independent
      of maternal behaviour.

PMID- 21852305
TI  - A deeper look into transcription regulatory code by preferred pair distance
      templates for transcription factor binding sites.
AB  - MOTIVATION: Modern experimental methods provide substantial information on
      protein-DNA recognition. Studying arrangements of transcription factor binding
      sites (TFBSs) of interacting transcription factors (TFs) advances understanding
      of the transcription regulatory code. RESULTS: We constructed binding motifs for
      TFs forming a complex with HIF-1alpha at the erythropoietin 3(')-enhancer.
      Corresponding TFBSs were predicted in the segments around transcription start
      sites (TSSs) of all human genes. Using the genome-wide set of regulatory regions,
      we observed several strongly preferred distances between hypoxia-responsive
      element (HRE) and binding sites of a particular cofactor protein. The set of
      preferred distances was called as a preferred pair distance template (PPDT). PPDT
      dramatically depended on the TF and orientation of its binding sites relative to
      HRE. PPDT evaluated from the genome-wide set of regulatory sequences was used to
      detect significant PPDT-consistent binding site pairs in regulatory regions of
      hypoxia-responsive genes. We believe PPDT can help to reveal the layout of
      eukaryotic regulatory segments. CONTACT: ivan.kulakovskiy@gmail.com SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 21852304
TI  - Improved quality control processing of peptide-centric LC-MS proteomics data.
AB  - MOTIVATION: In the analysis of differential peptide peak intensities (i.e.
      abundance measures), LC-MS analyses with poor quality peptide abundance data can
      bias downstream statistical analyses and hence the biological interpretation for
      an otherwise high-quality dataset. Although considerable effort has been placed
      on assuring the quality of the peptide identification with respect to spectral
      processing, to date quality assessment of the subsequent peptide abundance data
      matrix has been limited to a subjective visual inspection of run-by-run
      correlation or individual peptide components. Identifying statistical outliers is
      a critical step in the processing of proteomics data as many of the downstream
      statistical analyses [e.g. analysis of variance (ANOVA)] rely upon accurate
      estimates of sample variance, and their results are influenced by extreme values.
      RESULTS: We describe a novel multivariate statistical strategy for the
      identification of LC-MS runs with extreme peptide abundance distributions.
      Comparison with current method (run-by-run correlation) demonstrates a
      significantly better rate of identification of outlier runs by the multivariate
      strategy. Simulation studies also suggest that this strategy significantly
      outperforms correlation alone in the identification of statistically extreme
      liquid chromatography-mass spectrometry (LC-MS) runs. AVAILABILITY:
      https://www.biopilot.org/docs/Software/RMD.php CONTACT: bj@pnl.gov SUPPLEMENTARY
      INFORMATION: Supplementary material is available at Bioinformatics online.

PMID- 21852306
TI  - Effect of prolonged status epilepticus as a result of intoxication on
      epileptogenesis in a UK canine population.
AB  - The aim of the present study was to investigate if prolonged status epilepticus
      (SE), secondary to a chemoconvulsant, can induce spontaneous recurrent seizures
      in dogs. Clinical records at two UK referral hospitals were searched for dogs
      that presented in SE secondary to intoxication. Dogs were only included in the
      study if there was clear historical evidence of intoxication and a prolonged SE.
      Clinical and follow-up information was retrieved and verified by using a
      combination of clinical records from the two hospitals and the referring
      veterinarian and by contacting the owners using a telephone questionnaire. Twenty
      dogs met the inclusion criteria: 17 presented for metaldehyde toxicity, one for
      moxidectin toxicity, one for theobromine toxicity and one for mycotoxin toxicity.
      Of these 20 dogs, three dogs had an SE duration between 0.5 and one hour, four
      dogs between one and 12 hours, 10 dogs between 12 and 24 hours and three dogs
      greater then 24 hours. Median follow-up time for the 20 dogs was 757 days (range
      66 to 1663 days). No dog had any further seizures after its SE. The present study
      supports the view that dogs with a prolonged SE following intoxication with the
      aforementioned toxins might not need long-term treatment with antiepileptic drugs
      after the SE has been controlled.

PMID- 21852307
TI  - Chronic hepatitis in the English springer spaniel: clinical presentation,
      histological description and outcome.
AB  - Medical records and liver histology of 68 English springer spaniels (ESS) with a
      histological diagnosis of CH were reviewed retrospectively. PCR was performed on
      liver tissue for canine adenovirus-1 (CAV-1), canine parvovirus, canine
      herpesvirus and pathogenic Leptospira species. Follow-up information was obtained
      to calculate survival times. Median age at presentation was three years seven
      months (range, seven months to eight years five months) and there were 48 female
      and 20 male dogs. Clinical signs were non-specific and five dogs were
      asymptomatic. All dogs had an increase in serum activity of one or more
      hepatobiliary enzymes. Histopathology demonstrated hepatocyte necrosis and
      apoptosis with varying amounts of fibrosis. A predominantly lymphoplasmacytic
      infiltrate throughout the hepatic parenchyma was found in all 68 dogs, but 45 of
      these dogs also had a neutrophilic component to the inflammatory infiltrate.
      There was no significant copper accumulation and no aetiological agent was
      identified by PCR. The median survival time was 189 days (range, 1 to 1211 days),
      38 dogs died within three months and 12 dogs survived more than a year following
      diagnosis.

PMID- 21852308
TI  - Diagnosis of heart failure in elderly patients: a clinical challenge.

PMID- 21852310
TI  - Remote monitoring via implanted devices in heart failure: rising star or lame
      duck?

PMID- 21852311
TI  - Potential value of automated daily screening of cardiac resynchronization therapy
      defibrillator diagnostics for prediction of major cardiovascular events: results
      from Home-CARE (Home Monitoring in Cardiac Resynchronization Therapy) study.
AB  - AIM: To investigate whether diagnostic data from implanted cardiac
      resynchronization therapy defibrillators (CRT-Ds) retrieved automatically at 24 h
      intervals via a Home Monitoring function can enable dynamic prediction of
      cardiovascular hospitalization and death. METHODS AND RESULTS: Three hundred and
      seventy-seven heart failure patients received CRT-Ds with Home Monitoring option.
      Data on all deaths and hospitalizations due to cardiovascular reasons and Home
      Monitoring data were collected prospectively during 1-year follow-up to develop a
      predictive algorithm with a predefined specificity of 99.5%. Seven parameters
      were included in the algorithm: mean heart rate over 24 h, heart rate at rest,
      patient activity, frequency of ventricular extrasystoles, atrial-atrial intervals
      (heart rate variability), right ventricular pacing impedance, and painless shock
      impedance. The algorithm was developed using a 25-day monitoring window ending 3
      days before hospitalization or death. While the retrospective sensitivities of
      the individual parameters ranged from 23.6 to 50.0%, the combination of all
      parameters was 65.4% sensitive in detecting cardiovascular hospitalizations and
      deaths with 99.5% specificity (corresponding to 1.83 false-positive detections
      per patient-year of follow-up). The estimated relative risk of an event was 7.15
      fold higher after a positive predictor finding than after a negative predictor
      finding. CONCLUSION: We developed an automated algorithm for dynamic prediction
      of cardiovascular events in patients treated with CRT-D devices capable of daily
      transmission of their diagnostic data via Home Monitoring. This tool may increase
      patients' quality of life and reduce morbidity, mortality, and health economic
      burden, it now warrants prospective studies. ClinicalTrials.gov  NCT00376116.

PMID- 21852313
TI  - Development and evaluation of a combined story and fact-based educational booklet
      for patients with multiple brain metastases and their caregivers.
AB  - The aim of our study was to design and evaluate the impact on informational
      satisfaction of a combined story and fact-based educational booklet designed for
      patients with multiple brain metastases. Phase A evaluated the preference of
      participants for combined, fact, or story-based writing style. Based on these
      results, a resource was developed using a combined story and fact-based approach.
      Patients with newly diagnosed brain metastases and their caregivers read the
      booklet. Satisfaction was evaluated using the Information Satisfaction
      Questionnaire and Client Satisfaction Questionnaire. Anxiety was evaluated before
      and after reading using the State Trait Anxiety Inventory. Ninety-one patients
      participated in this study. In Phase A, 51% of patients expressed a preference
      for the combined story and fact-based approach. In phase B, participants
      expressed high satisfaction for both the informational content and the overall
      satisfaction towards the pamphlet. The level of anxiety before reading the
      booklet was lower for caregivers than patients. Anxiety score was increased in
      the caregiver group after reading the booklet. This was unchanged in the patient
      group. Both patients and caregivers endorsed the resource. The increase in
      anxiety in caregivers suggests the tool has been effective in conveying serious
      prognostic implications.

PMID- 21852314
TI  - End-of-life-care for Chinese patients in acute care ward setting: experience in
      an oncology ward and report on a pilot project on the use of an integrated care
      pathway.

PMID- 21852315
TI  - Seeking professional help for mental health problems, among New Zealand secondary
      school students.
AB  - OBJECTIVE: Our aim was to investigate whether secondary school students with
      mental health problems sought help from general practitioners and to investigate
      whether mental illness type, socio-demographic variables, family, school and
      community factors were associated with seeking help. METHOD: A randomly selected
      sample of 9699 secondary school students from across New Zealand participated in
      the Youth2000 Health and Wellbeing Survey. Data analysis included uni-variate and
      regression analyses. RESULTS: Having symptoms of anxiety (p<0.0001), depression
      (p<0.0001), and suicidal thoughts (p<0.0001) were associated with help seeking.
      However, 82%of students who had significant mental health problems had not sought
      help from a general practitioner. Rates of help seeking increased with age for
      girls and decreased with age for boys. Seeking help for mental health problems
      was also associated with living in a single parent family (p<0.0001), living in
      an over-crowded house (p=0.0006), and being well known by a teacher (p=0.0004).
      CONCLUSIONS: The majority of New Zealand secondary school students with mental
      health problems do not obtain the help they need from general practitioners.
      Given the prevalence of mental health problems, it is important to find ways of
      identifying adolescents with difficulties and encouraging them to seek help.

PMID- 21852316
TI  - Parents of adolescents who have committed sexual offenses: characteristics,
      challenges, and interventions.
AB  - This article discusses the importance of a systems approach to working with
      adolescents who have offended sexually. Literature concerning family backgrounds
      of these youths is reviewed, highlighting histories of family violence, parental
      depression and child maltreatment, problematic communication patterns, parental
      psychological inaccessibility, inconsistent discipline, and failure of the family
      to acknowledge the youth's offending behavior. Such issues and other special
      challenges presented by parents of these adolescents, particularly as the issues
      impact caregiver support and supervision, can be significant barriers to a
      youth's successful treatment. However, when these barriers are addressed through
      a systems approach that actively involves parents in assessment and therapeutic
      phases of intervention, treatment of an adolescent who sexually offended is
      likely to be enhanced. The importance of offering parents multiple intervention
      strategies at various stages in the therapeutic process is emphasized;
      interventions might include individual, family, and multi-family group therapy,
      and psychoeducation and support groups.

PMID- 21852317
TI  - Nigerian secondary school children's knowledge of and attitudes to mental health
      and illness.
AB  - BACKGROUND: Children tend to lack knowledge of, and hold negative attitudes
      towards mental illness. However, most of the work undertaken in Nigeria has been
      done with adults. AIMS: To establish the views and knowledge about mental health
      and illness in pupils at four secondary schools in rural and urban Southwest
      Nigeria. METHODS: A cross-sectional survey based on a questionnaire previously
      used in the UK and adapted to Nigeria. RESULTS: Data from 145 Nigerian
      schoolchildren showed little knowledge of, negative attitudes and social distance
      towards persons with mental health problems. Urban participants and boys appeared
      less knowledgeable than rural children and girls. CONCLUSIONS: Nigerian
      schoolchildren, as with Nigerian adults and young people in Western countries,
      show stigma towards mental illness. This may be underpinned by a lack of
      knowledge regarding mental health problems. Educational interventions need to be
      appropriate to area, age and gender to effectively improve mental health
      literacy, which in turn will influence attitudes and social distance. However,
      the fact that the schoolchildren were optimistic about recovery is a strength
      that could be built upon.

PMID- 21852318
TI  - A qualitative investigation into the maternal experience of having a young child
      with severe food allergy.
AB  - BACKGROUND: Severe food allergy has potentially life threatening consequences.
      Despite the significant impact on quality of life for families affected by food
      allergy, there is still relatively little known about the psychosocial experience
      in this area, especially with regards to the parenting experience. OBJECTIVES:
      This study focused on the following areas of parental experience: (1) having a
      young child with severe food allergy; (2) perception of the effect of food
      allergy on family relationships; (3) managing the challenges associated with
      severe food allergy. METHODS: Eight mothers of children with severe food allergy
      completed semi-structured interviews. Interview transcripts were analysed using
      Interpretative Phenomenological Analysis (IPA), a qualitative methodology.
      RESULTS: Three superordinate themes emerged from the analysis: (1) Parental
      adjustment-re-establishing an "even keel"; (2) It's a big responsibility: Living
      with risk; (3) Identity and the social aspects of allergy. This article focuses
      on the most psychologically salient findings within each of these superordinate
      themes. CONCLUSION: Mothers in this study shared similar concerns to mothers of
      children with other chronic illnesses. It is recommended that the experience of
      allergy should be viewed in the wider family context with specific consideration
      given to parental coping and anxiety. Services could better meet the
      psychological and social needs of those affected by allergy.

PMID- 21852319
TI  - Listening to parents: the challenges of parenting kindergarten-aged children who
      are anxious.
AB  - The purpose of this study was to increase understanding of the experience of
      parenting kindergarten-aged children who are anxious. Twenty-three in-depth
      interviews were conducted with parents of kindergarten-aged children who
      expressed interest in a parent-focused early intervention program for child
      anxiety offered in a local elementary school. Key concerns of the parents
      included their children's separation anxiety, social anxiety, and oppositional
      behaviour. The child's anxiety was identified as a stressor on the child, the
      parent, and the family. Parents utilized a range of parenting responses although
      they tended to be reactive and did not have a consistent strategy for managing
      the anxiety. A salient parenting struggle was whether or not to push the child to
      face challenging situations although there were few descriptions of
      overprotection or overcontrol. The findings suggest greater attention be given to
      the strengths of parents of children who are anxious and the ways in which
      parents may be a positive factor in mitigating the effects of child anxiety.
      Implications for intervention are discussed.

PMID- 21852320
TI  - Selective mutism: a home-and kindergarten-based intervention for children 3-5
      years: a pilot study.
AB  - The aim was to examine the outcome of a multimodal treatment for selective mutism
      (SM). Seven children, aged three-five years, who were referred for SM were
      included. The treatment started at home and was continued at kindergarten for a
      maximum of six months, with predefined treatment goals in terms of speaking
      levels, from I ("Speaks to the therapist in a separate room with a parent
      present") through to VI ("Speaks in all kindergarten settings without the
      therapist present"). The outcome measures were the teacher-reported School Speech
      Questionnaire (SSQ) and the treatment goal obtained (I-VI) six months after the
      onset of treatment, and the SSQ and Clinical Global Impression Scale (CGI) at one
      year follow-up. Six children spoke in all kindergarten settings (VI) after a mean
      of 14 weeks treatment. One child, with more extensive neuro-developmental delay,
      spoke in some settings only (V). The mean SSQ score was 0.59 (SD = 0.51) at
      baseline compared with 2.68 (SD = 0.35) at the six-month evaluation and 2.26 (SD
      = 0.93) at one-year follow-up. The mean CGI score at baseline was 4.43 (SD =
      0.79) compared with 1.14 (SD = 0.38) at follow-up. Home- and kindergarten-based
      treatment appears to be promising.

PMID- 21852321
TI  - Adopted children and education: the experiences of a specialist CAMHS team.
AB  - The education system makes special provision for "looked after children".
      However, once adopted these children become invisible. Adopted children are often
      placed in their new families when they are already of school age. School is yet
      another transition alongside that of home, food, language and social milieu which
      an adopted child has to manage together the pain of the loss of the biological
      family and its culture. This article focuses on the importance for CAMHS
      practitioners to work closely with schools and adoptive parents to help children
      manage their lives in school. Alongside the difficulties they face in learning,
      many adopted children need help in managing friendships and in concentrating on
      what is required of them in school. Adults may be ignorant of the day to day
      experiences of racism and questions about mothers, fathers, brothers and sisters
      that can throw an adopted child into confusion. This chapter draws on clinical
      experience to describe some of the difficulties that arise for parents and
      children in managing the education system.

PMID- 21852322
TI  - Mind-mindedness in parents of pre-schoolers: a comparison between clinical and
      community samples.
AB  - Mind-mindedness relates to parents' propensity to treat their young children as
      individuals with minds of their own. Research with community samples has
      demonstrated impressive findings regarding child development outcomes, leading to
      a suggestion that mind-mindedness should be considered in clinical interventions.
      This is the first mind-mindedness study to include parents of children referred
      to clinical services. A between group design (n=49) was used to investigate
      whether mind-mindedness differed between parents of a clinical group of pre
      school children and parents of a community comparison group and to explore how
      mind-mindedness related to parental depression and stress, and child
      difficulties. The findings revealed that mind-mindedness was significantly lower
      in the clinical sample and was not related to depression in either group. In the
      clinical group mind-mindedness was related to parenting stress and in the
      community group it was related to children's emotional and behavioural
      difficulties. Overall these findings provide preliminary evidence that mind
      mindedness may be an important construct to consider in pre-school clinical
      interventions.

PMID- 21852323
TI  - Surveillance of rare diseases: a public health evaluation of the British
      Paediatric Surveillance Unit.
AB  - BACKGROUND: The British Paediatric Surveillance Unit (BPSU), a joint undertaking
      between the Royal College of Paediatrics and Child Health, Institute of Child
      Health and Health Protection Agency, undertakes nationwide surveillance of rare
      paediatric disorders. In 2007-09, formal evaluation to examine its effectiveness
      commenced. METHODS: Centres of Disease Control guidelines for appraising public
      health surveillance systems were applied. Data sources included BPSU databases,
      published and unpublished reports. Questionnaires were sent to 600 participating
      paediatricians and 27 researchers. Half of the questionnaires were administered
      online to assess the feasibility of electronic reporting. RESULTS: Three thousand
      UK paediatricians report monthly to the BPSU (94% return) and eighty BPSU studies
      have been published. These studies have influenced immunization and screening
      policy, altered clinical practice and informed health service configuration.
      Surveillance operations are simple, stable, representative and responsive to
      changing demands. Returns from the paediatricians' survey were 75%; investigators
      89%. Paediatricians valued the BPSU and did not find participation burdensome.
      Most supported online questionnaires (56%) but not monthly electronic reporting
      (35%). CONCLUSIONS: Evaluation demonstrated the effectiveness of the BPSU as a
      valuable resource for clinicians and policy-makers. Opportunities identified for
      future development include secure online reporting, improved responsiveness to
      urgent health threats and promoting public involvement.

PMID- 21852325
TI  - Pluripotency-associated stem cell marker expression in proliferative cell
      cultures derived from adult human pancreas.
AB  - The source of new beta-cells in adult human pancreas remains incompletely
      elucidated with recent studies on rodents providing evidence for neogenesis from
      progenitor cells in addition to self-replication. The aim of this study was to
      investigate the expression of pluripotency-associated stem cell markers in
      proliferative cultures derived from adult human pancreas. Human pancreatic tissue
      was obtained from deceased donors following ethical approval and relative
      consent. Islet-enriched fraction was separated from the retrieved organ by
      digestion and density gradient centrifugation. Dissociated cells were seeded in
      adherent culture forming proliferative 'islet survivor cells' (ISCs). These were
      characterised at fifth passage by RT-PCR, immunofluorescence staining, FACS,
      western blot and transfection studies with an OCT4 promoter-driven reporter.
      Nuclear expression of the pluripotency-associated stem cell marker complex
      OCT4/SOX2/NANOG was confirmed in ISCs. The phenotype constituted ~8% of the
      overall population. OCT4 biosynthesis was confirmed by western blot and
      activation of an exogenous OCT4 promoter. Co-expression of pluripotency
      associated markers has been confirmed in proliferative primary cells derived from
      adult human pancreas. Further studies are required to elucidate whether these
      cells possess functional stem cell characteristics and assess potential for
      differentiation into pancreatic cell lineages including new beta-cells.

PMID- 21852324
TI  - Mitogen-activated protein kinase phosphatase 1 regulates bone mass, osteoblast
      gene expression, and responsiveness to parathyroid hormone.
AB  - Parathyroid hormone (PTH) signaling via PTH 1 receptor (PTH1R) involves mitogen
      activated protein kinase (MAPK) pathways. MAPK phosphatase 1 (MKP1)
      dephosphorylates and inactivates MAPKs in osteoblasts, the bone-forming cells. We
      previously showed that PTH1R activation in differentiated osteoblasts upregulates
      MKP1 and downregulates pERK1/2-MAPK and cyclin D1. In this study, we evaluated
      the skeletal phenotype of Mkp1 knockout (KO) mice and the effects of PTH in vivo
      and in vitro. Microcomputed tomography analysis of proximal tibiae and distal
      femora from 12-week-old Mkp1 KO female mice revealed osteopenic phenotype with
      significant reduction (8-46%) in bone parameters compared with wild-type (WT)
      controls. Histomorphometric analysis showed decreased trabecular bone area in KO
      females. Levels of serum osteocalcin (OCN) were lower and serum tartrate
      resistant acid phosphatase 5b (TRAP5b) was higher in KO animals. Treatment of
      neonatal mice with hPTH (1-34) for 3 weeks showed attenuated anabolic responses
      in the distal femora of KO mice compared with WT mice. Primary osteoblasts
      derived from KO mice displayed delayed differentiation determined by alkaline
      phosphatase activity, and reduced expressions of Ocn and Runx2 genes associated
      with osteoblast maturation and function. Cells from KO females exhibited
      attenuated PTH response in mineralized nodule formation in vitro. Remarkably,
      this observation was correlated with decreased PTH response of matrix Gla protein
      expression. Expressions of pERK1/2 and cyclin D1 were inhibited dramatically by
      PTH in differentiated osteoblasts from WT mice but much less in osteoblasts from
      Mkp1 KO mice. In conclusion, MKP1 is important for bone homeostasis, osteoblast
      differentiation and skeletal responsiveness to PTH.

PMID- 21852326
TI  - Synthesis, base pairing properties and trans-lesion synthesis by reverse
      transcriptases of oligoribonucleotides containing the oxidatively damaged base 5
      hydroxycytidine.
AB  - The synthesis of a caged RNA phosphoramidite building block containing the
      oxidatively damaged base 5-hydroxycytidine (5-HOrC) has been accomplished. To
      determine the effect of this highly mutagenic lesion on complementary base
      recognition and coding properties, this building block was incorporated into a 12
      mer oligoribonucleotide for T(m) and CD measurements and a 31-mer template strand
      for primer extension experiments with HIV-, AMV- and MMLV-reverse transcriptase
      (RT). In UV-melting experiments, we find an unusual biphasic transition with two
      distinct T(m)'s when 5-HOrC is paired against a DNA or RNA complement with the
      base guanine in opposing position. The higher T(m) closely matches that of a C-G
      base pair while the lower is close to that of a C-A mismatch. In single
      nucleotide extension reactions, we find substantial misincorporation of dAMP and
      to a lesser extent dTMP, with dAMP almost equaling that of the parent dGMP in the
      case of HIV-RT. A working hypothesis for the biphasic melting transition does not
      invoke tautomeric variability of 5-HOrC but rather local structural perturbations
      of the base pair at low temperature induced by interactions of the 5-HO group
      with the phosphate backbone. The properties of this RNA damage is discussed in
      the context of its putative biological function.

PMID- 21852327
TI  - Characterization of the DNA binding specificity of Shelterin complexes.
AB  - The Shelterin complex associates with telomeres and plays an essential role in
      telomere protection and telomerase regulation. In its most abundant form, the
      complex is composed of six core components: TRF1, TRF2, POT1, TIN2, TPP1 and
      RAP1. Of these subunits, three can interact directly with either single-stranded
      (POT1) or double-stranded (TRF1, TRF2) telomeric DNA. In this report, we have
      developed assays to measure the DNA binding activity of Shelterin complexes in
      human cell extracts. With these assays, we have characterized the composition and
      DNA binding specificity of two Shelterin complexes: a 6-member complex that
      contains all six core components and a second complex that lacks TRF1. Our
      results show that both of these complexes bind with high affinity (K(D) = 1.3-1.5
      * 10(-9) M) and selectively to ds/ss-DNA junctions that carry both a binding site
      for POT1 (ss-TTAGGGTTAG) and a binding site for the SANT/Myb domain of TRF1 or
      TRF2 (ds-TTAGGGTTA). This DNA binding specificity suggests the preferential
      recruitment of these complexes to areas of the telomere where ss- and ds-DNA are
      in close proximity, such as the 3'-telomeric overhang, telomeric DNA bubbles and
      the D-loop at the base of T-loops.

PMID- 21852328
TI  - The SRSF1 linker induces semi-conservative ESE binding by cooperating with the
      RRMs.
AB  - SR proteins promote spliceosome formation by recognizing exonic splicing
      enhancers (ESEs) during pre-mRNA splicing. Each SR protein binds diverse ESEs
      using strategies that are yet to be elucidated. Here, we show that the RNA
      binding domain (RBD) of SRSF1 optimally binds to decameric purine rich ESE
      sequences although locations of purines are not stringently specified. The
      presence of uracils either within or outside of the recognition site is
      detrimental for binding with SRSF1. The entire RBD, comprised of two RRMs and a
      glycine-rich linker, is essential for ESE binding. Mutation within each segment
      reduced or nearly abolished binding, suggesting that these segments mediate
      cooperative binding. The linker plays a decisive role in organizing ESE binding.
      The flanking basic regions of the linker appear to communicate with each other in
      bringing the two RRMs close together to form the complex with RNA. Our study thus
      suggests semi-conservative adaptable interaction between ESE and SRSF1, and such
      binding mode is not only essential for the recognition of plethora of
      physiological ESE sequences but may also be essential for the interaction with
      various factors during the spliceosome assembly.

PMID- 21852329
TI  - Targeted isolation of cloned genomic regions by recombineering for haplotype
      phasing and isogenic targeting.
AB  - Studying genetic variations in the human genome is important for understanding
      phenotypes and complex traits, including rare personal variations and their
      associations with disease. The interpretation of polymorphisms requires reliable
      methods to isolate natural genetic variations, including combinations of
      variations, in a format suitable for downstream analysis. Here, we describe a
      strategy for targeted isolation of large regions (~35 kb) from human genomes that
      is also applicable to any genome of interest. The method relies on recombineering
      to fish out target fosmid clones from pools and thereby circumvents the laborious
      need to plate and screen thousands of individual clones. To optimize the method,
      a new highly recombineering-efficient bacterial host, including inducible TrfA
      for fosmid copy number amplification, was developed. Various regions were
      isolated from human embryonic stem cell lines and a personal genome, including
      highly repetitive and duplicated ones. The maternal and paternal alleles at the
      MECP2/IRAK 1 loci were distinguished based on identification of novel allele
      specific single-nucleotide polymorphisms in regulatory regions. Additionally, we
      applied further recombineering to construct isogenic targeting vectors for
      patient-specific applications. These methods will facilitate work to understand
      the linkage between personal variations and disease propensity, as well as
      possibilities for personal genome surgery.

PMID- 21852330
TI  - Day-night variations in endothelial dysfunction markers and haemostatic factors
      in sleep apnoea.
AB  - Patients with sleep apnoea have a significant alteration in the day-night pattern
      of myocardial infarction and sudden cardiac death observed in the general
      population. The aim of this study was to investigate the influence of sleep
      apnoea on the diurnal variations in various haemostatic parameters (factor VII,
      von Willebrand factor and plasminogen activator inhibitor (PAI)-1) and markers of
      endothelial dysfunction (asymmetric dimethylarginine (ADMA) and soluble CD40
      ligand (sCD40L)). We studied 26 male patients with obstructive sleep apnoea
      syndrome (OSAS; 13 patients with severe OSAS (apnoea/hypopnoea index (AHI) >30
      events . h(-1)) and 13 patients with mild-to-moderate OSAS (AHI <30 events . h(
      1))) and 12 controls of similar body mass index (BMI) and waist circumference. In
      each subject, six different samples were obtained over 24 h. Although all the
      markers values tended to be higher in patients with severe OSAS, differences did
      not reach statistical significance at any time. PAI-1 levels were significantly
      related to BMI (p<0.001), mean (p<0.001) and minimal (p = 0.047) nocturnal
      oxygenation saturation. ADMA levels were significantly related to arousal index
      (p = 0.046). The results of this study suggest that day-night variations in
      factor VII:antigen (Ag), von Willebrand factor:Ag, PAI-1, sCD40L and ADMA levels
      may be dependent on either the obesity index or metabolic dysfunction rather than
      on sleep apnoea alone.

PMID- 21852331
TI  - RSV infection modulates IL-15 production and MICA levels in respiratory
      epithelial cells.
AB  - The cytokine interleukin (IL)-15, major histocompatibility complex (MHC) class I
      molecules and MHC class I chain-related proteins (MIC) A and B are involved in
      cellular immune responses to virus infections but their role in respiratory
      syncytial virus (RSV) infection has not been studied. We aimed to determine how
      RSV infection modulates IL-15 production, MHC class I and MICA expression in
      respiratory epithelial cells, the molecular pathways implicated in virus-induced
      IL-15 production and how interferon (IFN)-gamma alters RSV-induced IL-15
      production and MHC class I and MICA expression. We infected respiratory
      epithelial cell lines (A549 and BEAS-2B cells) and primary bronchial epithelial
      cells with RSV and measured production of IL-15, expression of MHC I and MICA and
      the role of the transcription factor nuclear factor (NF)-kappaB. We report here
      that RSV increases IL-15 in respiratory epithelial cells via virus replication
      and NF-kappaB-dependent mechanisms. Furthermore, RSV infection of epithelial
      cells upregulated cell surface expression of MICA and levels of soluble MICA. IFN
      gamma upregulated RSV induction of soluble IL-15 but inhibited induction of MICA.
      Upregulation of IL-15, MHC I and MICA are likely to be important mechanisms in
      activating immune responses to RSV by epithelial cells.

PMID- 21852332
TI  - Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre
      trial.
AB  - Forceps, brushes or needles are currently the standard tools used during flexible
      bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique
      of cryobiopsy appears to provide better diagnostic samples. The aim of this study
      was to evaluate cryobiopsy over conventional endobronchial sampling. A total of
      600 patients in eight centres with suspected endobronchial tumours were included
      in a prospective, randomised, single-blinded multicentre study. Patients were
      randomised to either sampling using forceps or the cryoprobe. After obtaining
      biopsy samples, a blinded histological evaluation was performed. According to the
      definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated
      by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a
      final diagnosis of cancer. 281 patients were randomised to receive endobronchial
      biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe.
      A definitive diagnosis was achieved in 85.1% of patients randomised to
      conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy
      (p<0.001). Importantly, there was no difference in the incidence of significant
      bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic
      yield in comparison with conventional forceps biopsy.

PMID- 21852333
TI  - Breastfeeding is associated with increased lung function at 18 years of age: a
      cohort study.
AB  - Breastfeeding has been linked with increased forced vital capacity (FVC) in
      children but not in older adolescents. Our aim was to investigate the effects of
      breastfeeding duration and infant weight gain on FVC in both developmental
      periods. In a birth cohort, information on breastfeeding duration was collected
      at 1 and 2 yrs; spirometric tests were conducted at 10 and 18 yrs. To estimate
      the effect of breastfeeding duration on FVC at 18 yrs of age, we used linear
      models; to analyse repeated FVC measurements at 10 and 18 yrs of age, we used
      linear mixed models. Links between breastfeeding, infant weight gain and FVC at
      10 and 18 yrs of age were analysed through path analyses. Among 808 breastfed
      children, 49% were breastfed for >= 4 months. At 18 yrs of age the augmenting
      effect of breastfeeding on FVC was reduced with increased height. Linear mixed
      models identified that breastfeeding duration was associated with increased FVC.
      Path analysis suggested a direct effect of breastfeeding on FVC at 10 yrs of age,
      but an indirect effect at 18 yrs of age via FVC at 10 yrs of age. Although
      inversely related to breastfeeding, a higher weight gain in infants led to taller
      adolescents and, in turn, resulted in increased FVC. In conclusion, a longer
      duration of breastfeeding contributes to lung health in childhood and
      adolescence.

PMID- 21852334
TI  - Home telemonitoring (forced expiratory volume in 1 s) in children with severe
      asthma does not reduce exacerbations.
AB  - Some children with severe asthma develop frequent exacerbations despite intensive
      treatment. We sought to assess the outcome (severe exacerbations and healthcare
      use, lung function, quality of life and maintenance treatment) of a strategy
      based on daily home spirometry with teletransmission to an expert medical centre
      and whether it differs from that of a conventional strategy. 50 children with
      severe uncontrolled asthma were enrolled in a 12-month prospective study and were
      randomised into two groups: 1) treatment managed with daily home spirometry and
      medical feedback (HM) and 2) conventional treatment (CT). The children's mean age
      was 10.9 yrs (95% confidence interval 10.2-11.6). 44 children completed the study
      (21 in the HM group and 23 in the CT group). The median number of severe
      exacerbations per patient was 2.0 (interquartile range 1.0-4.0) in the HM group
      and 3.0 (1.0-4.0) in the CT group (p=0.38 with adjustment for age). There were no
      significant differences between the two groups for unscheduled visits (HM 5.0
      (3.0-7.0), CT 3.0 (2.0-7.0); p=0.30), lung function (pre-beta(2)-agonist forced
      expiratory volume in 1 s (FEV(1)) p=0.13), Paediatric Asthma Quality of Life
      Questionnaire scores (p=0.61) and median daily dose of inhaled corticosteroids
      (p=0.86). A treatment strategy based on daily FEV(1) monitoring with medical
      feedback did not reduce severe asthma exacerbations.

PMID- 21852335
TI  - Cigarette smoke inhibits lung fibroblast proliferation by translational
      mechanisms.
AB  - Cigarette smoke is a major cause of chronic obstructive pulmonary disease (COPD)
      and emphysema. Although cigarette smoke represses cellular proliferation, the
      molecular mechanisms underlying this phenomenon are unknown. CCAAT/enhancer
      binding proteins (C/EBPs) are key regulators of cell cycle progression,
      differentiation and pro-inflammatory gene expression, are regulated predominantly
      at the translational level and may be involved in the pathogenesis of COPD. The
      aim of this study was to assess the effect of cigarette smoke on proliferation
      and the expression and translational regulation of C/EBPalpha and C/EBPbeta in
      nondiseased primary human lung fibroblasts. Fibroblasts were exposed to cigarette
      smoke-conditioned medium (10% and 20% for 24 h). Proliferation was determined by
      [(3)H]thymidine incorporation. Protein expression levels were determined by
      immunoblotting and translation was monitored using a translation control reporter
      system. Cigarette smoke significantly reduced fibroblast proliferation and
      significantly upregulated full-length C/EBPalpha and C/EBPbeta proteins due to a
      shift in the translational control of CEBPA and CEBPB mRNAs. This shift involved
      the re-initiation of mRNA translation via the regulatory upstream open reading
      frame, which coincided with increased interleukin-8 release and a decrease in
      functional elastin level. These findings provide a novel mechanism to
      understanding the tissue remodelling observed in the lungs of COPD patients.

PMID- 21852336
TI  - Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up.
AB  - The association between bronchiolitis and recurrent wheezing remains
      controversial. In this prospective study, we assessed risk factors for recurrent
      wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised
      for their first episode of bronchiolitis. Demographic, clinical and laboratory
      data were obtained with a questionnaire and from medical files. A total of 14
      respiratory viruses were concurrently assayed in nasal washings. Parents were
      interviewed 12 months after hospitalisation to check whether their infants
      experienced recurrent wheezing. The rate of recurrent wheezing was higher in
      infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001).
      Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0
      11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2-4.9)
      as major independent risk factors for recurrent wheezing. In conclusion, the
      virus most likely to be associated with recurrent wheezing at 12 months after
      initial bronchiolitis is RV, a viral agent that could predict infants prone to
      the development of recurrent wheezing.

PMID- 21852337
TI  - Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling
      phenomenon.
AB  - Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled
      breath of patients may represent the ideal specimen for future lung cancer
      screening. However, the clinical applicability of current diagnostic sensor
      technologies based on signal pattern analysis remains incalculable due to their
      inability to identify a clear target. To test the robustness of the presence of a
      so far unknown volatile organic compound in the breath of patients with lung
      cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy
      individuals, confirmed lung cancer or chronic obstructive pulmonary disease
      (COPD)) were presented to sniffer dogs following a rigid scientific protocol.
      Patient history, drug administration and clinicopathological data were analysed
      to identify potential bias or confounders. Lung cancer was identified with an
      overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was
      independent from COPD and the presence of tobacco smoke and food odours. Logistic
      regression identified two drugs as potential confounders. It must be assumed that
      a robust and specific volatile organic compound (or pattern) is present in the
      breath of patients with lung cancer. Additional research efforts are required to
      overcome the current technical limitations of electronic sensor technologies to
      engineer a clinically applicable screening tool.

PMID- 21852338
TI  - Rapid early weight gain is associated with wheeze and reduced lung function in
      childhood.
AB  - The aim of our study was to investigate the association between rapid weight gain
      in the first 3 months of life and the prevalence of wheeze in the first years of
      life and lung function at 5 yrs of age. The infants selected were participating
      in an ongoing birth cohort. Information on growth and respiratory symptoms was
      collected during the first year of life, and on primary care consultations during
      total follow-up. Forced expiratory volume in 1 s (FEV(1)) and forced expiratory
      flow at 25-75% of forced vital capacity (FEF(25-75%)) were measured at 5 yrs of
      age. Information on growth and respiratory symptoms was obtained for 1,431
      infants, out of whom 235 children had already had 5 yrs of follow-up. Every one
      point z-score increase in weight gain resulted in a 37% increase in days with
      wheeze (incidence rate ratio 1.37, 95% CI 1.27-1.47; p<0.001) and in associated
      consultations by 16% (incidence rate ratio 1.16, 95% CI 1.01-1.34; p=0.04).
      Children with rapid weight gain reported significantly more physician-diagnosed
      asthma. FEV(1) and FEF(25-75%) were reduced by 34 mL (adjusted regression
      coefficient -0.034, 95% CI -0.056- -0.013; p=0.002) and 82 mL (adjusted
      regression coefficient -0.082, 95% CI -0.140- -0.024; p=0.006) per every one
      point z-score increase in weight gain, respectively. These associations were
      independent of birthweight. Rapid early weight gain is a risk factor for
      clinically relevant wheezing illnesses in the first years of life and lower lung
      function in childhood.

PMID- 21852339
TI  - Dietary factors and lung function in the general population: wine and resveratrol
      intake.
AB  - Wine intake is associated with a better lung function in the general population,
      yet the source of this effect is unknown. Resveratrol, a polyphenol in wine, has
      anti-inflammatory properties in the lung, its effects being partially mediated
      via induction of Sirtuin (SIRT)1 activity. We assessed the impact of wine and
      resveratrol intake, and SIRT1 single-nucleotide polymorphisms (SNPs) on lung
      function in the general population. Effects of red and white wine and resveratrol
      intake on forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC)
      and FEV(1)/FVC were analysed in the population-based Doetinchem cohort (n=3,224).
      Associations of four tagging SIRT1 SNPs with lung function were analysed in the
      Doetinchem (n=1,152) and Vlagtwedde-Vlaardingen (n=1,390) cohorts. Resveratrol
      intake was associated with higher FVC levels, and white wine intake with higher
      FEV(1) levels and lower risk of airway obstruction. SIRT1 SNPs were not
      significantly associated with level or course of lung function, either directly
      or indirectly via wine or resveratrol intake. This study shows a positive
      association of resveratrol intake with lung function in the general population,
      confirms the previously reported positive association of white wine intake with
      higher levels of FEV(1), and additionally shows an association with a higher
      FEV(1)/FVC ratio. These effects probably do not run via SNPs in SIRT1.

PMID- 21852340
TI  - Electronic monitoring and feedback to improve adherence in pediatric asthma.
AB  - OBJECTIVE: To evaluate the effectiveness of electronic monitoring and feedback to
      improve adherence in children taking daily asthma controller medications. METHOD:
      Five patients with asthma and considered nonadherent participated. Inhalers were
      electronically monitored with the MDILogII(TM) device, and feedback was given by
      medical staff. Using a nonconcurrent multiple-baseline design, patients and their
      parents received bimonthly feedback regarding medication use. Following
      treatment, feedback was withdrawn and effects of monitoring alone were observed.
      RESULTS: Three participants showed improvements in adherence following treatment,
      with more notable increases when baseline adherence was low. Improvements in the
      inhaler technique occurred for all patients. Some patients demonstrated
      improvements in lung functioning and functional severity. When feedback was
      withdrawn, adherence decreased for some participants, but technique improvements
      maintained. CONCLUSIONS: Results support the use of objective monitoring devices
      for assessing pediatric asthma patients' adherence and indicate that feedback
      from medical staff may improve and maintain medication adherence for some
      patients.

PMID- 21852341
TI  - The traumatic impact of motor vehicle accidents in high school students.
AB  - OBJECTIVES: To obtain the year prevalence of nonfatal motor vehicle accidents
      (MVAs) in adolescents, to describe trauma symptoms (posttraumatic stress,
      depression, anxiety, dissociation), and to test a theoretical model of traumatic
      events. METHODS: A community-based sample of 3,007 adolescents (mean age: 14.6
      years) completed questionnaires regarding MVAs, appraisals, coping, support, and
      trauma symptoms. RESULTS: Three percent of the adolescents reported being injured
      in a MVA during the past year. Of the adolescents who reported a MVA in their
      life (22.4%), 11.0% reported significant posttraumatic stress or other trauma
      symptoms. Structural equation modeling revealed that negative appraisals mediated
      the relation between trauma symptoms and MVA severity. Avoidant coping partially
      mediated the relation between appraisal and trauma symptoms. Social support was
      associated with less negative appraisals and with more avoidant coping.
      CONCLUSIONS: Results suggest the need for a better registration of young traffic
      victims to optimize screening for psychological problems.

PMID- 21852342
TI  - High peer popularity longitudinally predicts adolescent health risk behavior, or
      does it?: an examination of linear and quadratic associations.
AB  - OBJECTIVE: In contrast to prior work, recent theory suggests that high, not low,
      levels of adolescent peer popularity may be associated with health risk behavior.
      This study examined (a) whether popularity may be uniquely associated with
      cigarette use, marijuana use, and sexual risk behavior, beyond the predictive
      effects of aggression; (b) whether the longitudinal association between
      popularity and health risk behavior may be curvilinear; and (c) gender
      moderation. METHODS: A total of 336 adolescents, initially in 10-11th grades,
      reported cigarette use, marijuana use, and number of sexual intercourse partners
      at two time points 18 months apart. Sociometric peer nominations were used to
      examine popularity and aggression. RESULTS: Longitudinal quadratic effects and
      gender moderation suggest that both high and low levels of popularity predict
      some, but not all, health risk behaviors. CONCLUSIONS: New theoretical models can
      be useful for understanding the complex manner in which health risk behaviors may
      be reinforced within the peer context.

PMID- 21852343
TI  - Comparison of a family-based group intervention for youths with obesity to a
      brief individual family intervention: a practical clinical trial of positively
      fit.
AB  - OBJECTIVE: To examine the effectiveness of a family-based behavioral group
      intervention (Positively Fit; PF) for pediatric obesity relative to a brief
      family intervention (BFI) in a sample of treatment-seeking children and
      adolescents. METHODS: Families (n = 93) were randomized to treatment condition.
      Assessments were conducted at pre- and posttreatment and at 12-month follow-up.
      Outcome indices included standardized body mass index (BMI) and quality of life
      (QOL). RESULTS: Results indicated a significant reduction in zBMI at
      posttreatment and follow-up across both conditions. At follow-up, BFI and PF
      participants evidenced average reductions of .12 and .19 zBMI units,
      respectively. Children demonstrated better outcomes than adolescents across both
      conditions. Results indicated clinically significant improvements in parent
      reported QOL at postintervention and in self-reported QOL at follow-up for PF
      participants. CONCLUSIONS: Results suggest the effectiveness of family-based
      interventions for pediatric obesity in clinical settings among younger children.
      Neither intervention was effective in terms of reducing zBMI among adolescents.

PMID- 21852344
TI  - Outcomes of population based language promotion for slow to talk toddlers at ages
      2 and 3 years: Let's Learn Language cluster randomised controlled trial.
AB  - OBJECTIVE: To determine the benefits of a low intensity parent-toddler language
      promotion programme delivered to toddlers identified as slow to talk on screening
      in universal services. DESIGN: Cluster randomised trial nested in a population
      based survey. SETTING: Three local government areas in Melbourne, Australia.
      PARTICIPANTS: Parents attending 12 month well child checks over a six month
      period completed a baseline questionnaire. At 18 months, children at or below the
      20th centile on an expressive vocabulary checklist entered the trial.
      INTERVENTION: Maternal and child health centres (clusters) were randomly
      allocated to intervention (modified "You Make the Difference" programme over six
      weekly sessions) or control ("usual care") arms. MAIN OUTCOME MEASURES: The
      primary outcome was expressive language (Preschool Language Scale-4) at 2 and 3
      years; secondary outcomes were receptive language at 2 and 3 years, vocabulary
      checklist raw score at 2 and 3 years, Expressive Vocabulary Test at 3 years, and
      Child Behavior Checklist/1.5-5 raw score at 2 and 3 years. RESULTS: 1217 parents
      completed the baseline survey; 1138 (93.5%) completed the 18 month checklist,
      when 301 (26.4%) children had vocabulary scores at or below the 20th centile and
      were randomised (158 intervention, 143 control). 115 (73%) intervention parents
      attended at least one session (mean 4.5 sessions), and most reported high
      satisfaction with the programme. Interim outcomes at age 2 years were similar in
      the two groups. Similarly, at age 3 years, adjusted mean differences
      (intervention-control) were -2.4 (95% confidence interval -6.2 to 1.4; P=0.21)
      for expressive language; -0.3 (-4.2 to 3.7; P=0.90) for receptive language; 4.1 (
      2.3 to 10.6; P=0.21) for vocabulary checklist; -0.5 (-4.4 to 3.4; P=0.80) for
      Expressive Vocabulary Test; -0.1 (-1.6 to 1.4; P=0.86) for externalising
      behaviour problems; and -0.1 (-1.3 to 1.2; P=0. 92) for internalising behaviour
      problems. CONCLUSION: This community based programme targeting slow to talk
      toddlers was feasible and acceptable, but little evidence was found that it
      improved language or behaviour either immediately or at age 3 years. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN20953675.

PMID- 21852345
TI  - Health services across Europe face cuts as debt crisis begins to bite.

PMID- 21852346
TI  - Doctors join protest over change to FDA rules on conflict of interest.

PMID- 21852347
TI  - Transcript and metabolite analysis of the Trichoderma-induced systemic resistance
      response to Pseudomonas syringae in Arabidopsis thaliana.
AB  - In the present study we have assessed, by transcriptional and metabolic
      profiling, the systemic defence response of Arabidopsis thaliana plants to the
      leaf pathogen Pseudomonas syringae pv. tomato DC3000 (Pst) induced by the
      beneficial fungus Trichoderma asperelloides T203. Expression analysis (qPCR) of a
      set of 137 Arabidopsis genes related to Pst defence responses showed that T203
      root colonization is not associated with major detectable transcriptomic changes
      in leaves. However, plants challenged with the bacterial pathogen showed
      quantitative differences in gene expression when pre-inoculated with T203,
      supporting priming of the plant by this beneficial fungus. Among the defence
      related genes affected by T203, lipid transfer protein (LTP)4, which encodes a
      member of the lipid transfer pathogenesis-related family, is upregulated, whereas
      the WRKY40 transcription factor, known to contribute to Arabidopsis
      susceptibility to bacterial infection, shows reduced expression. On the other
      hand, root colonization by this beneficial fungus substantially alters the plant
      metabolic profile, including significant changes in amino acids, polyamines,
      sugars and citric acid cycle intermediates. This may in part reflect an increased
      energy supply required for the activation of plant defences and growth promotion
      effects mediated by Trichoderma species.

PMID- 21852348
TI  - Variability of neuD transcription levels and capsular sialic acid expression
      among serotype III group B Streptococcus strains.
AB  - Serotype III group B Streptococcus (GBS) is the major cause of neonatal
      meningitis, but the risk of infection in the colonized neonates is variable.
      Capsular sialic acid (Sia), whose synthesis is encoded by neu genes, appears to
      be a major virulence factor in several bacterial species able to reach the
      cerebrospinal fluid. Therefore, variations of Sia expression related to the
      genetic diversity of strains may have an impact on the risk of meningitis in
      colonized neonates. We characterized by MLST the phylogenetic diversity of 64
      serotype III GBS strains isolated from vaginal flora and randomly selected. These
      strains mostly belonged to three major sequence types (STs): ST1 (11%), ST17
      (39%) and ST19 (31%). The genetic diversity of strains of these lineages,
      characterized by PFGE, allowed the selection of 17 representative strains, three
      ST1, six ST17 and eight ST19, with NEM316 as reference, in order to evaluate (i)
      by quantitative RT-PCR, the level of transcription of the neuD gene as a marker
      for the transcription of neu genes and (ii) by enzymological analysis, the
      expression of Sia. The mean transcription level of neuD was higher for ST17
      strains than for ST1 and ST19 strains in the early, mid- and late exponential
      growth phases, and was maximum in the early exponential growth phase for ST17
      strains and in the mid-exponential growth phase for ST1 and ST19 strains. Mean
      Sia concentration was higher for ST17 than for ST1 and ST9 strains in all three
      growth phases. For the total population, Sia concentration varied notably in the
      stationary phase, from 0.38 to 9.30 nmol per 10(8) viable bacteria, with a median
      value of 2.99 nmol per 10(8) bacteria. All ST17 strains, only one-third of the
      ST19 strains and none of the ST1 strains had Sia concentrations higher than the
      median Sia concentration. Therefore, differences in the level of expression of
      Sia by strains of the major serotype III GBS phylogenetic lineages might be one
      of the factors that explain the leading role of ST17 strains in neonatal
      meningitis.

PMID- 21852349
TI  - A Francisella tularensis SCHU S4 mutant deficient in gamma-glutamyltransferase
      activity induces protective immunity: characterization of an attenuated vaccine
      candidate.
AB  - Francisella tularensis is an intracellular pathogen which causes tularaemia.
      There is no licensed vaccine currently available for prophylaxis. The gamma
      glutamyl transpeptidase (GGT) encoded by the ggt gene has been shown to be
      important for the intracellular survival of F. tularensis. In this study we have
      constructed a ggt deletion mutant in the highly virulent F. tularensis strain
      SCHU S4. Characterization of the mutant strain confirmed the function of ggt, and
      confirmed the role of GGT in cysteine acquisition. The mutant strain was highly
      attenuated both in vitro and in vivo using murine models of infection. Moreover,
      we have demonstrated that the attenuated mutant is able to induce protective
      immunity against an F. tularensis SCHU S4 challenge, and thus may be a candidate
      for the development of an attenuated vaccine.

PMID- 21852350
TI  - Biochemical characterization of the tetrahydrobiopterin synthesis pathway in the
      oleaginous fungus Mortierella alpina.
AB  - We characterized the de novo biosynthetic pathway of tetrahydrobiopterin (BH4) in
      the lipid-producing fungus Mortierella alpina. The BH4 cofactor is essential for
      various cell processes, and is probably present in every cell or tissue of higher
      organisms. Genes encoding two copies of GTP cyclohydrolase I (GTPCH-1 and GTPCH
      2) for the conversion of GTP to dihydroneopterin triphosphate (H2-NTP), 6
      pyruvoyltetrahydropterin synthase (PTPS) for the conversion of H2-NTP to 6
      pyruvoyltetrahydropterin (PPH4), and sepiapterin reductase (SR) for the
      conversion of PPH4 to BH4, were expressed heterologously in Escherichia coli. The
      recombinant enzymes were produced as His-tagged fusion proteins and were purified
      to homogeneity to investigate their enzymic activities. Enzyme products were
      analysed by HPLC and electrospray ionization-MS. Kinetic parameters and other
      properties of GTPCH, PTPS and SR were investigated. Physiological roles of BH4 in
      M. alpina are discussed, and comparative analyses between GTPCH, PTPS and SR
      proteins and other homologous proteins were performed. The presence of two
      functional GTPCH enzymes has, as far as we are aware, not been reported
      previously, reflecting the unique ability of this fungus to synthesize both BH4
      and folate, using the GTPCH product as a common substrate. To our knowledge, this
      study is the first to report the comprehensive characterization of a BH4
      biosynthesis pathway in a fungus.

PMID- 21852351
TI  - Single nucleotide polypmorphisms of fimH associated with adherence and biofilm
      formation by serovars of Salmonella enterica.
AB  - Type 1 fimbriae produced by serovars of Salmonella are characterized by their
      ability to agglutinate guinea pig erythrocytes in the absence of d-mannose but
      not in its presence. The FimH protein is the adhesin that mediates this reaction;
      it is distinct from the major fimbrial protei.n (FimA) that composes the fimbrial
      shaft. Avian-adapted serovars of Salmonella produce non-haemagglutinating
      fimbriae that have been reported to mediate adherence to avian cells. A single
      amino acid substitution is present in the FimH adhesin of these strains compared
      to that of a Typhimurium isolate. Also, previous studies have shown that single
      nucleotide polymorphisms in two strains of the Typhimurium fimH alter the binding
      specificity. We therefore investigated the allelic variation of fimH from a range
      of serotypes (both host-adapted and non-host-adapted) and isolates of Salmonella.
      Most FimH adhesins mediated the mannose-sensitive haemagglutination of guinea pig
      erythrocytes, but many did not facilitate adherence to HEp-2 cells. A small
      number of isolates also produced fimbriae but did not mediate adherence to either
      cell type. Transformants possessing cloned fimH genes exhibited a number of
      different substitutions within the predicted amino acid sequence of the FimH
      polypeptide. No identical FimH amino sequence was found between strains that
      adhere to erythrocytes and/or HEp-2 cells and those produced by non-adherent
      strains. FimH-mediated adherence to HEp-2 cells was invariably associated with
      the ability to form biofilms on mannosylated bovine serum albumin.

PMID- 21852352
TI  - Atomic force microscopy of a ctpA mutant in Rhizobium leguminosarum reveals
      surface defects linking CtpA function to biofilm formation.
AB  - Atomic force microscopy was used to investigate the surface ultrastructure,
      adhesive properties and biofilm formation of Rhizobium leguminosarum and a ctpA
      mutant strain. The surface ultrastructure of wild-type R. leguminosarum consists
      of tightly packed surface subunits, whereas the ctpA mutant has much larger
      subunits with loose lateral packing. The ctpA mutant strain is not capable of
      developing fully mature biofilms, consistent with its altered surface
      ultrastructure, greater roughness and stronger adhesion to hydrophilic surfaces.
      For both strains, surface roughness and adhesive forces increased as a function
      of calcium ion concentration, and for each, biofilms were thicker at higher
      calcium concentrations.

PMID- 21852353
TI  - Risk of bias from inclusion of patients who already have diagnosis of or are
      undergoing treatment for depression in diagnostic accuracy studies of screening
      tools for depression: systematic review.
AB  - OBJECTIVES: To investigate the proportion of original studies included in
      systematic reviews and meta-analyses on the diagnostic accuracy of screening
      tools for depression that appropriately exclude patients who already have a
      diagnosis of or are receiving treatment for depression and to determine whether
      these systematic reviews and meta-analyses evaluate possible bias from the
      inclusion of such patients. DESIGN: Systematic review. DATA SOURCES: Medline,
      PsycINFO, CINAHL, Embase, ISI, SCOPUS, and Cochrane databases were searched from
      1 January 2005 to 29 October 2009. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
      Systematic reviews and meta-analyses in any language that reported on the
      diagnostic accuracy of screening tools for depression. RESULTS: Only eight of 197
      (4%) unique publications from 17 systematic reviews and meta-analyses
      specifically excluded patients who already had a diagnosis of or were receiving
      treatment for depression. No systematic reviews or meta-analyses commented on
      possible bias from the inclusion of such patients, even though 10 reviews used
      quality assessment tools with items to rate risk of bias from composition of the
      sample of patients. CONCLUSIONS: Studies of the accuracy of screening tools for
      depression rarely exclude patients who already have a diagnosis of or are
      receiving treatment for depression, a potential bias that is not evaluated in
      systematic reviews and meta-analyses. This could result in inflated estimates of
      accuracy on which clinical practice and preventive care guidelines are often
      based, a problem that takes on greater importance as the rate of diagnosed and
      treated depression in the population increases.

PMID- 21852354
TI  - Differential role of PKA catalytic subunits in mediating phenotypes caused by
      knockout of the Carney complex gene Prkar1a.
AB  - The Carney complex is an inherited tumor predisposition caused by activation of
      the cAMP-dependent protein kinase [protein kinase A (PKA)] resulting from
      mutation of the PKA-regulatory subunit gene PRKAR1A. Myxomas and tumors in cAMP
      responsive tissues are cardinal features of this syndrome, which is unsurprising
      given the important role played by PKA in modulating cell growth and function.
      Previous studies demonstrated that cardiac-specific knockout of Prkar1a causes
      embryonic heart failure and myxomatous degeneration in the heart, whereas limited
      Schwann cell-specific knockout of the gene causes schwannoma formation. In this
      study, we sought to determine the role of PKA activation in this phenotype by
      using genetic means to reduce PKA enzymatic activity. To accomplish this goal, we
      introduced null alleles of the PKA catalytic subunits Prkaca (Ca) or Prkacb (Cb)
      into the Prkar1a-cardiac knockout (R1a-CKO) or limited Schwann cell knockout (R1a
      TEC3KO) line. Heterozygosity for Prkaca rescued the embryonic lethality of the
      R1a-CKO, although mice had a shorter than normal lifespan and died from cardiac
      failure with atrial thrombosis. In contrast, heterozygosity for Prkacb only
      enabled the mice to survive 1 extra day during embryogenesis. Biochemical
      analysis indicated that reduction of Ca markedly reduced PKA activity in
      embryonic hearts, whereas reduction of Cb had minimal effects. In R1a-TEC3KO
      mice, tumorigenesis was completely suppressed by a heterozygosity for Prkaca, and
      by more than 80% by heterozygosity for Prkacb. These data suggest that both
      developmental and tumor phenotypes caused by Prkar1a mutation result from excess
      PKA activity due to PKA-Ca.

PMID- 21852355
TI  - Targeting somatostatin receptors: preclinical evaluation of novel 18F
      fluoroethyltriazole-Tyr3-octreotate analogs for PET.
AB  - The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors has
      been increasing over the past 3 decades. Because of high densities of
      somatostatin receptors (sstr)--mainly sstr-2--on the cell surface of these
      tumors, (111)In-diethylenetriaminepentaacetic acid-octreotide scintigraphy has
      become an important part of clinical management. (18)F-radiolabeled analogs with
      suitable pharmacokinetics would permit PET with more rapid clinical protocols.
      METHODS: We compared the affinity in vitro and tissue pharmacokinetics by PET of
      5 structurally related (19)F/(18)F-fluoroethyltriazole-Tyr(3)-octreotate (FET
      TOCA) analogs: FET-G-polyethylene glycol (PEG)-TOCA, FETE-PEG-TOCA, FET-G-TOCA,
      FETE-TOCA, and FET-betaAG-TOCA to the recently described (18)F-aluminum fluoride
      NOTA-octreotide ((18)F-AIF-NOTA-OC) and the clinical radiotracer (68)Ga-DOTATATE.
      RESULTS: All (19)F-fluoroethyltriazole-Tyr(3)-octreotate compounds retained high
      agonist binding affinity to sstr-2 in vitro (half-maximal effective
      concentration, 4-19 nM vs. somatostatin at 5.6 nM). Dynamic PET showed that
      incorporation of PEG linkers, exemplified by (18)F-FET-G-PEG-TOCA and (18)F-FETE
      PEG-TOCA, reduced uptake in high sstr-2-expressing AR42J pancreatic cancer
      xenografts. (18)F-FET-betaAG-TOCA showed the lowest nonspecific uptake in the
      liver. Tumor uptake increased in the order (68)Ga-DOTATATE < (18)F-AIF-NOTA <=
      (18)F-FET-betaAG-TOCA < (18)F-FET-G-TOCA. The uptake of (18)F-FET-betaAG-TOCA was
      specific: a radiolabeled scrambled peptide, (18)F-FET-betaAG-[W-c-(CTFTYC)K], did
      not show tumor uptake; there was lower uptake of (18)F-FET-betaAG-TOCA in AR42J
      xenografts when mice were pretreated with 10 mg of unlabeled octreotide per
      kilogram; and there was low uptake of (18)F-FET-betaAG-TOCA in low sstr-2
      expressing HCT116 xenografts. CONCLUSION: We have developed novel
      fluoroethyltriazole-Tyr(3)-octreotate radioligands that combine high specific
      binding with rapid target localization and rapid pharmacokinetics for high
      contrast PET. (18)F-FET-betaAG-TOCA and (18)F-FET-G-TOCA are candidates for
      future clinical evaluation.

PMID- 21852356
TI  - Prognostic value of 18F-FDG PET in monosegmental stenosis and myelopathy of the
      cervical spinal cord.
AB  - MRI offers perfect visualization of spondylotic stenosis of the cervical spine,
      but morphologic imaging does not correlate with clinical symptoms and
      postoperative recovery after decompression surgery. In this prospective study, we
      investigated the role of (18)F-FDG PET in patients with degenerative stenosis of
      the cervical spinal cord in relation to postsurgical outcome. METHODS: Twenty
      patients with monosegmental spondylotic stenosis of the middle cervical spine
      (C3/C4 or C4/C5) showing intramedullary hyperintensity on T2-weighted MRI and
      clinical symptoms of myelopathy (myelopathic patients) were investigated by (18)F
      FDG PET. Maximum standardized uptake values (SUV(max)) were measured at all
      levels of the cervical spine (C1-C7). Decompression surgery and anterior cervical
      fusion were performed on all patients, and clinical status (Japanese Orthopedic
      Association [JOA] score) was assessed before and 6 mo after surgery. The (18)F
      FDG data of 10 individuals without cervical spine pathology were used as a
      reference (controls). RESULTS: The myelopathic patients showed a significant
      decrease in (18)F-FDG uptake in the area of the lower cervical cord, compared
      with the control group (C7 SUV(max), 1.49 +/- 0.18 vs. 1.71 +/- 0.27, P = 0.01).
      Ten myelopathic patients exhibited focally increased (18)F-FDG uptake at the
      level of the stenosis (SUV(max), 2.27 +/- 0.41 vs. 1.75 +/- 0.22, P = 0.002). The
      remaining 10 patients showed inconspicuous (18)F-FDG uptake at the area of the
      stenosis. Postoperatively, the patients with focally increased (18)F-FDG
      accumulation at the level of stenosis showed good clinical recovery and a
      significant improvement in JOA scores (13.6 +/- 2.3 vs. 9.5 +/- 2.5, P = 0.001),
      whereas no significant improvement was observed in the remaining patients (JOA
      score, 12.0 +/- 2.4 vs. 11.6 +/- 2.5, not statistically significant). Multiple
      regression analysis identified the presence of focally increased (18)F-FDG uptake
      at the level of the stenosis as an independent predictor of postoperative outcome
      (P = 0.002). CONCLUSION: The results suggest that regional changes in (18)F-FDG
      uptake have prognostic significance in compression-induced cervical myelopathy
      that may be helpful in decisions on the timing of surgery.

PMID- 21852357
TI  - First clinical evidence that imaging with somatostatin receptor antagonists is
      feasible.
AB  - Preclinical studies have indicated that somatostatin receptor (sst)-expressing
      tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst
      agonists. In this study, we evaluated whether imaging with sst antagonists was
      feasible in patients. METHODS: Biodistribution and tumor uptake of the sst
      antagonist (111)In-DOTA-pNO(2)-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)DTyrNH(2) ((111)In
      DOTA-BASS) were studied in 5 patients with metastatic thyroid carcinoma or
      neuroendocrine tumors. Findings were compared with (111)In-pentetreotid ((111)In
      DTPA-octreotide) scan. RESULTS: No adverse effects of (111)In-DOTA-BASS (20 MUg)
      were observed. (111)In-DOTA-BASS detected 25 of 28 lesions, whereas (111)In-DTPA
      octreotide detected only 17 of 28 lesions. In the same patient, (111)In-DOTA-BASS
      showed higher tumor and lower renal uptake than (111)In-DTPA-octreotide (3.5 +/-
      2.8 percentage injected activity [%IA] vs. 1.0 +/- 0.99%IA and 1.5 +/- 0.3 %IA
      vs. 2.3 +/- 0.7 %IA) at 4 h after injection. CONCLUSION: Imaging of
      neuroendocrine tumors with sst antagonists is clinically feasible. The favorable
      human biodistribution data suggest that sst antagonists could significantly
      affect peptide receptor-mediated imaging and therapy.

PMID- 21852358
TI  - Euro-American discussion document on entry-level and advanced practice in nuclear
      medicine.

PMID- 21852359
TI  - Identification of reference genes for RT-qPCR expression analysis in Arabidopsis
      and tomato seeds.
AB  - Quantifying gene expression levels is an important research tool to understand
      biological systems. Reverse transcription-quantitative real-time PCR (RT-qPCR) is
      the preferred method for targeted gene expression measurements because of its
      sensitivity and reproducibility. However, normalization, necessary to correct for
      sample input and reverse transcriptase efficiency, is a crucial step to obtain
      reliable RT-qPCR results. Stably expressed genes (i.e. genes whose expression is
      not affected by the treatment or developmental stage under study) are
      indispensable for accurate normalization of RT-qPCR experiments. Lack of accurate
      normalization could affect the results and may lead to false conclusions. Since
      transcriptomes of seeds are different from other plant tissues, we aimed to
      identify reference genes specifically for RT-qPCR analyses in seeds of two
      important seed model species, i.e. Arabidopsis and tomato. We mined Arabidopsis
      seed microarray data to identify stably expressed genes and analyzed these
      together with putative reference genes from other sources. In total, the
      expression stability of 24 putative reference genes was validated by RT-qPCR in
      Arabidopsis seed samples. For tomato, we lacked transcriptome data sets of seeds
      and therefore we tested the tomato homologs of the reference genes found for
      Arabidopsis seeds. In conclusion, we identified 14 Arabidopsis and nine tomato
      reference genes. This provides a valuable resource for accurate normalization of
      gene expression experiments in seed research for two important seed model
      species.

PMID- 21852360
TI  - Secretin is not necessary for exocrine pancreatic development and growth in mice.
AB  - Adaptive exocrine pancreatic growth is mediated primarily by dietary protein and
      the gastrointestinal hormone cholecystokinin (CCK). Feeding trypsin inhibitors
      such as camostat (FOY-305) is known to induce CCK release and stimulate
      pancreatic growth. However, camostat has also been reported to stimulate secretin
      release and, because secretin often potentiates the action of CCK, it could
      participate in the growth response. Our aim was to test the role of secretin in
      pancreatic development and adaptive growth through the use of C57BL/6 mice with
      genetic deletion of secretin or secretin receptor. The lack of secretin in the
      intestine or the secretin receptor in the pancreas was confirmed by RT-PCR. Other
      related components, such as vasoactive intestinal polypeptide (VIP) receptors
      (VPAC(1) and VPAC(2)), were not affected. Secretin increased cAMP levels in acini
      from wild-type (WT) mice but had no effect on acini from secretin receptor
      deleted mice, whereas VIP and forskolin still induced a normal response. Secretin
      in vivo failed to induce fluid secretion in receptor-deficient mice. The pancreas
      of secretin or secretin receptor-deficient mice was of normal size and histology,
      indicating that secretin is not necessary for normal pancreatic differentiation
      or maintenance. When WT mice were fed 0.1% camostat in powdered chow, the
      pancreas doubled in size in 1 wk, accompanied by parallel increases in protein
      and DNA. Camostat-fed littermate secretin and secretin receptor-deficient mice
      had similar pancreatic mass to WT mice. These results indicate that secretin is
      not required for normal pancreatic development or adaptive growth mediated by
      CCK.

PMID- 21852361
TI  - Esophageal sensation in premature human neonates: temporal relationships and
      implications of aerodigestive reflexes and electrocortical arousals.
AB  - Electrocortical arousal (ECA) as an effect of visceral provocation or of its
      temporal relationships with aerodigestive reflexes in premature neonates is not
      known. We tested the hypothesis that esophageal provocation results in both
      esophageal reflex responses and ECAs during sleep and that ECAs are dependent on
      the frequency characteristics of esophageal neuromotor responses. We defined the
      spatiotemporal relationship of ECAs in relation to 1) spontaneous
      pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and
      2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy
      premature neonates born at 27.9 +/- 3.4 wk were tested at 36.8 +/- 1.9 wk
      postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in
      sleep during concurrent manometry and videopolysomnography. With stimulus onset
      as reference point, we scored the response latency, frequency occurrence and
      duration of arousals, peristaltic reflex, and upper esophageal sphincter
      contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and
      esophageal sensory-motor parameters were scored by blinded observers.
      Significantly (for each characteristic listed, P < 0.05), swallow sequences were
      associated with arousals and sleep state changes, and arousals were associated
      with incomplete peristalsis, response delays to lower esophageal sphincter
      relaxation, and prolonged esophageal clearance. GER events (73.5%) provoked
      arousals, and arousals were associated with response delays to peristaltic
      reflexes or clearance, sleep state modification, and prolonged respiratory
      arousal. Midesophageal stimuli (54%) provoked arousals and were associated with
      increased frequency, prolonged latency, prolonged response duration of
      peristaltic reflexes and UESCR, and increased frequency of sleep state changes
      and respiratory arousals. In human neonates, ECAs are provoked upon esophageal
      stimulation; the sensory-motor characteristics of esophageal reflexes are
      distinct when accompanied by arousals. Aerodigestive homeostasis is defended by
      multiple tiers of aerodigestive safety mechanisms, and when esophageal reflexes
      are delayed, cortical hypervigilance (ECAs) occurs.

PMID- 21852362
TI  - Menin and JunD regulate gastrin gene expression through proximal DNA elements.
AB  - Mutations in the MEN1 gene correlate with multiple endocrine neoplasia I (MEN1).
      Gastrinomas are the most malignant of the neuroendocrine tumors associated with
      MEN1. Because menin and JunD proteins interact, we examined whether JunD binds to
      and regulates the gastrin gene promoter. Both menin and JunD are ubiquitous
      nuclear proteins that we showed colocalize in the gastrin-expressing G cells of
      the mouse antrum. Transfection with a JunD expression vector alone induced
      endogenous gastrin mRNA in AGS human gastric cells, and the induction was blocked
      by menin overexpression. We mapped repression by menin to both a nonconsensus AP
      1 site and proximal GC-rich elements within the human gastrin promoter. Chromatin
      immunoprecipitation assays, EMSAs, and DNA affinity precipitation assays
      documented that JunD and Sp1 proteins bind these two elements and are both
      targets for menin regulation. Consistent with menin forming a complex with
      histone deacetylases, we found that repression of gastrin gene expression by
      menin was reversed by trichostatin A. In conclusion, proximal DNA elements within
      the human gastrin gene promoter mediate interactions between JunD, which induces
      gastrin gene expression and menin, which suppresses JunD-mediated activation.

PMID- 21852363
TI  - Assessment of the protective effects of oral tocotrienols in arginine chronic
      like pancreatitis.
AB  - Tocotrienols exhibit anti-inflammatory properties over macrophages and promote
      cytotoxicity in activated pancreatic stellate cells, suggesting that they may
      limit chronic pancreatitis progression. We aimed to quantitate the effect of oral
      tocotrienols on a rat model of chronic pancreatic injury. Chronic-like
      pancreatitis was induced by repeated arginine pancreatitis. Palm oil tocotrienol
      rich fraction (TRF) was given by gavage before and after pancreatitis inductions.
      Amylase and hydroxyproline were determined in pancreatic homogenates; collagen,
      fibronectin, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein
      (GFAP), and phosphorylated Smad3 were assessed by Western blotting. Transforming
      growth factor (TGF)-beta1 was measured in plasma. Morphological assessment
      included light microscopy, fibrosis area fraction, and collagen network fractal
      analysis. Arginine pancreatitis induced pancreatic atrophy and increased
      hydroxyproline that ameliorated after TRF. Arginine increased TGF-beta1 (185 +/-
      40 vs. 15 +/- 2 ng/ml; P <0.01) that was blunted by TRF (53 +/- 19; P < 0.01).
      TRF reduced protease and Smad3 activation, collagen, and fibronectin. alpha-SMA
      increased and GFAP diminished in arginine pancreatitis, consistent with long-term
      stellate cell activation, and TRF reverted these changes to basal. Arginine
      pancreatitis increased fibrosis area fraction (4.5 +/- 0.3% vs. 0.2 +/- 0.2%),
      collagen network complexity (fractal dimension 1.52 +/- 0.03 vs. 1.42 +/- 0.01; P
      < 0.001), and inhomogeneity (lacunarity 0.63 +/- 0.03 vs. 0.40 +/- 0.02; P <
      0.001), which were all reduced by TRF (1.3 +/- 0.4%, 1.43 +/- 0.02%, and 0.51 +/-
      0.03%, respectively; P < 0.01). Best correlation coefficients were obtained when
      comparing fibrosis area fraction with lacunarity (r = 0.88) and both parameters
      with pancreatic weight (r = -0.91 and -0.79, respectively). TRF administered only
      before pancreatitis best, but not fully, recapitulated the beneficial effects of
      TRF. Tocotrienols improve quantitative measures of chronic pancreatic damage.
      They may be of benefit in human chronic pancreatitis.

PMID- 21852364
TI  - Exploration of the copper-related compensatory response in the Belgrade rat model
      of genetic iron deficiency.
AB  - The Menkes copper ATPase (Atp7a) and metallothionein (Mt1a) are induced in the
      duodenum of iron-deficient rats, and serum and hepatic copper levels increase.
      Induction of a multi-copper ferroxidase (ceruloplasmin; Cp) has also been
      documented. These findings hint at an important role for Cu during iron
      deficiency. The intestinal divalent metal transporter 1 (Dmt1) is also induced
      during iron deficiency. The hypothesis that Dmt1 is involved in the copper
      related compensatory response during iron deficiency was tested, utilizing a
      mutant Dmt1 rat model, namely the Belgrade (b/b) rat. Data from b/b rats were
      compared with phenotypically normal, heterozygous +/b rats. Intestinal Atp7a and
      Dmt1 expression was increased in b/b rats, whereas Mt1a expression was unchanged.
      Serum and liver copper levels did not increase in the Belgrades nor did Cp
      protein or activity. The lack of fully functional Dmt1 may thus partially blunt
      the compensatory response to iron deficiency by 1) decreasing copper levels in
      enterocytes, as exemplified by a lack of Mt1a induction and a lesser induction of
      Atp7a, 2) abolishing the frequently described increase in liver and serum copper,
      and 3) attenuating the documented increase in Cp expression and activity.

PMID- 21852365
TI  - Gastric electrical stimulation parameter dependently alters ventral medial
      hypothalamic activity and feeding in obese rats.
AB  - Gastric electrical stimulation (GES) has been used to treat obesity with unclear
      mechanisms and limited parameter ranges. This study explores effects of GES
      parameters on ventral medial hypothalamic (VMH) activity, feeding, and body
      weight in diet-induced obese (DIO) rats. For experiment 1, discharge rates were
      recorded in 39 gastric distension-responsive (GD-R) neurons in 12 DIO rats. Basal
      rates were compared with rates under GES using varied pulse amplitudes, widths,
      frequencies, and train-on times. For experiment 2, a crossover experiment in 16
      DIO rats measured food intake and weight effects of GES pulse width, the
      parameter with the steepest neuronal response gradient in experiment 1.
      Treatments were sham and 0.5-, 2.0-, and 5.0-ms pulse GES. In experiment 1, 11 of
      13 GES parameter sets tested produced significantly (P < 0.05) altered discharge
      rates of GD-R neurons. Increases in pulse amplitude (P < 0.05) and width (P <
      0.0001) produced significant upward linear trends in response over the range
      tested, with the trend being strongest for pulse width. In experiment 2, over 4
      days of 0.5-, 2.0-, and 5.0-ms GES treatment, food intake was 9.6% (P < 0.05),
      21.0% (P < 0.0001), and 47.3% (P < 0.0001) lower than under sham-GES, whereas
      body weight changes were 0.7 (P = 0.48), 2.2 (P < 0.05), and 3.5 (P < 0.002)
      percentage points lower, respectively. We concluded that GES pulse width
      increases had the largest effect on VMH neuronal activity, and these effects were
      paralleled by pulse width-dependent reductions in food intake and body weight.
      Lengthening pulse width beyond the range used in prior clinical studies may be
      critical to making GES a viable obesity treatment.

PMID- 21852367
TI  - Species differences in distribution and prediction of human V(ss) from
      preclinical data.
AB  - Prediction of human volume of distribution at steady state (V(ss)) before first
      administration of a new drug candidate to humans has become an important part of
      the drug development process. This study examines the assumptions behind
      interspecies scaling techniques used to predict human V(ss) from preclinical
      data, namely the equivalency of V(ss,u) and/or f(ut) across species. In addition,
      several interspecies scaling techniques are evaluated side by side using a set of
      67 reference compounds where observed V(ss) from rats, dogs, monkeys, and humans
      were compiled from the literature and where plasma protein binding was determined
      across species using an ultracentrifugation technique. Species similarity in
      V(ss,u) or f(ut) does not appear to be the norm among rats, dogs, monkeys, or
      humans. Despite this, interspecies scaling from rats, dogs, and monkeys is useful
      and can provide reasonably accurate predictions of human V(ss), although some
      interspecies scaling approaches were better than others. For example, the
      performance of the common V(ss,u) or f(ut) equivalency approaches using average
      V(ss,u) or f(ut) across three preclinical species was superior to allometric
      scaling techniques. In addition, considering data from several preclinical
      species, using the equivalency approach, was superior to scaling from any single
      species. Although the mechanistic tissue composition equations available in the
      Simcyp population-based pharmacokinetic simulator did not necessarily provide the
      most accurate predictions, and the equations used likely need refinement, they
      still provide the best opportunity for a mechanistic understanding and prediction
      of human V(ss).

PMID- 21852366
TI  - Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis.
AB  - The causes of fibrosis, or the inappropriate wound healing, that follows chronic
      intestinal inflammation are not well defined and likely involve the contributions
      of multiple cellular mechanisms. As other articles in this series confirm,
      inflammatory cytokines clearly play a role in driving cell differentiation to the
      myofibroblast phenotype, promoting proliferation and extracellular matrix
      deposition that are characteristic of fibrotic tissue. However, controlling the
      balance of cytokines produced and process of myofibroblast differentiation
      appears to be more complex. This review considers ways in which hyaluronan, an
      extracellular matrix component that is remodeled during the progression of
      colitis, may provide indirect as well as direct cues that influence the balancing
      act of intestinal wound healing.

PMID- 21852368
TI  - Optimal presentation modes for detecting brain tumor progression.
AB  - BACKGROUND AND PURPOSE: A common task in radiology interpretation is visual
      comparison of images. The purpose of this study was to compare traditional side
      by-side and in-place (flicker) image presentation modes with advanced methods for
      detecting primary brain tumors on MR imaging. MATERIALS AND METHODS: We
      identified 66 patients with gliomas and 3 consecutive brain MR imaging
      examinations (a "triplet"). A display application that presented images in side
      by-side mode with or without flicker display as well as display of image
      subtraction or automated change detection information (also with and without
      flicker display) was used by 3 board-certified neuroradiologists. They identified
      regions of brain tumor progression by using this display application. Each case
      was reviewed using all modes (side-by-side presentation with and without flicker,
      subtraction with and without flicker, and change detection with and without
      flicker), with results compared via a panel rating. RESULTS: Automated change
      detection with or without flicker (P < .0027) as well as subtraction with or
      without flicker (P < .0027) were more sensitive to tumor progression than side-by
      side presentation in cases where all 3 raters agreed. Change detection afforded
      the highest interrater agreement, followed by subtraction. Clinically determined
      time to progression was longer for cases rated as nonprogressing by using
      subtraction images and change-detection images both with and without flicker
      display mode compared with side-by-side presentation. CONCLUSIONS: Automated
      change detection and image subtraction, with and without flicker display mode,
      are superior to side-by-side image comparison.

PMID- 21852369
TI  - Correlation between preoperative pain duration and percutaneous vertebroplasty
      outcome.
AB  - BACKGROUND AND PURPOSE: The duration of the fracture is considered by many
      practitioners to be an important predictor of outcome following vertebroplasty.
      We sought to define the impact of preprocedural pain duration on outcomes,
      including pain relief, improvement in function, and medication usage among
      patients treated with single-level vertebroplasty. MATERIALS AND METHODS:
      Institutional review board approval was obtained before conducting this
      retrospective analysis of 321 patients undergoing single-level vertebroplasty at
      our institution. Fractures were categorized as acute (<=6 weeks, n = 153),
      subacute (6-24 weeks, n = 124), and chronic (>24 weeks, n = 44). Pain NRS (0-10)
      scores at rest and with activity and RDS were compared among 3 groups at baseline
      and post procedure. Also absolute and proportional improvement of pain NRS and
      RDS were compared among 3 groups by using ANOVA. Linear regression was performed
      between preoperative pain duration and symptom improvement for each group.
      RESULTS: Baseline RDS and pain NRS with activity and at rest were not
      significantly different among groups (P = .09, .30, and .91, respectively). Mean
      improvement in pain NRS with activity at 1 month postvertebroplasty in acute
      (improvement = 4.9 +/- 3.5), subacute (improvement = 4.2 +/- 3.2), and chronic
      fractures (improvement = 4.5 +/- 3.2) was similar among groups (P = .28). Mean
      improvement in RDS at 1 month postprocedure was 9.6, 8.3, and 9.9, for acute,
      subacute, and chronic fractures, respectively (P = .56). There was no strong
      correlation between length of pain and symptom improvement. CONCLUSIONS: The age
      of fracture has minimal impact on outcome following single-level vertebroplasty,
      with good outcomes noted among patients with acute, subacute, and chronic
      fractures.

PMID- 21852370
TI  - A case of delayed encephalopathy after carbon monoxide poisoning longitudinally
      monitored by diffusion tensor imaging.
AB  - A woman with DE after CO poisoning was longitudinally evaluated by DTI, performed
      during the following periods: at the phase of acute CO poisoning, the lucid
      interval, neurologic deterioration due to DE, and neurologic recovery. The
      present case revealed the long-term course of DTI parameters after CO poisoning
      and the usefulness of DTI for quantifying neurologic damage after CO poisoning.

PMID- 21852371
TI  - Tectorial membrane injury: frequently overlooked in pediatric traumatic head
      injury.
AB  - REHs and tectorial membrane injuries are rare complications of pediatric head and
      neck injuries. We aim to describe the neuroimaging findings in pediatric REHs, to
      summarize the mechanism of injury, and to correlate the imaging findings with the
      clinical presentation. We retrospectively evaluated CT and/or MR imaging studies
      of 10 children with traumatic REH. Most patients were involved in MVAs. The
      tectorial membrane was injured in 70% of patients, and REHs were medium to large
      in 80%. None of the patients had a focal spinal cord or brain stem injury,
      craniocervical junction dislocation, or vertebral fractures. Tectorial membrane
      disruption was diagnosed in most patients without craniocervical junction-related
      symptoms. Tectorial membrane lesions and REHs were seen in young children who
      sustained high-speed head and neck injuries. Clinical symptoms may be minimal or
      misleading. The radiologist should be aware of these injuries in children. MR
      imaging appears to be more sensitive than CT.

PMID- 21852372
TI  - A flow-diverting stent is not a pressure-diverting stent.
AB  - The approach for treatment of large and fusiform intracranial aneurysms has
      evolved from stent-assisted coiling to treatment with flow-diverting stents. The
      treatment results for these stents are promising; however, early postprocedural
      aneurysm rupture has been described. The exact cause of rupture is unknown but
      might be related to intra-aneurysmal flow and pressure changes. We measured intra
      aneurysmal pressure before, during, and after placement of a flow-diverting stent
      by using a dual-sensor guidewire. The pressure inside the aneurysm momentarily
      decreased during placement but was restored to baseline values within minutes.
      The flow-diverting stent does not seem to protect the aneurysm from the stress
      induced by pressure or pressure changes within the lumen.

PMID- 21852373
TI  - Experimental study and optimization of scan parameters that influence radiation
      dose in temporal bone high-resolution multidetector row CT.
AB  - BACKGROUND AND PURPOSE: MDCT has some specific scan parameters that may
      systematically increase or decrease radiation dose to patients. This study
      explored the scan protocol parameters that impact radiation dose in temporal bone
      MDCT and determined the optimal scan parameters that balance radiation dose with
      diagnostic image quality. MATERIALS AND METHODS: Using exsomatized cadaveric
      heads, traditional axial scanning, and helical scanning were performed with
      different detector collimations. Helical scans of the same scan region were then
      acquired by using the determined optimal detector collimation and various tube
      voltages, whereas other scan parameters remained fixed. Next, the scans were
      repeated by using various tube current-time products by using the determined
      optimal tube voltage. Last, with fixed tube current-time product, the scans were
      repeated with various pitches. All thin-section, helically acquired scans were
      reformatted to axial and coronal images with respect to the relevant scanning
      baseline. In each of the image volumes, the mean and SD HU values in regions of
      interest were measured in the central section of the internal auditory canal, and
      CNR values were calculated. RESULTS: In agreement with theory, wider detector
      collimations such as 16 * 0.625 mm and 64 * 0.625 mm were associated with lower
      radiation doses than narrower collimations due to their lower overbeaming and
      higher geometric efficiency. In helical scanning, the detector collimation of 16
      * 0.625 mm had higher image quality and the minimum DLP. Axial and coronal images
      acquired by using a 140-kVp tube voltage had significantly lower noise than scans
      acquired at 120 or 80 kVp with equivalent volume CT dose index. Diagnostic image
      quality was achieved when using a minimum tube current-time product of 120 mAs.
      Noise, CNR, and dose were jointly optimized with a pitch of 0.685. CONCLUSIONS:
      Temporal bone CT scanning parameters may be optimized by following a systematic
      procedure that allows for the optimization of diagnostic image quality and the
      minimization of radiation dose. One such procedure for a particular 64-section
      MDCT scanner has been presented.

PMID- 21852374
TI  - High-resolution double inversion recovery black-blood imaging of cervical artery
      dissection using 3T MR imaging.
AB  - SUMMARY: We performed high-resolution DIR-BBI of the cervical arteries at 3T in
      19 subjects with cervical dissection. It offered excellent visualization of both
      the lumen and arterial wall, allowing detection of the primary and secondary
      features of dissection. We suggest that this is a highly useful technique for
      diagnosis of cervical dissection, either routinely or in equivocal cases of
      suspected dissection. It also offers further insight into the pathogenesis of
      this disorder.

PMID- 21852376
TI  - Percutaneous and open retrograde endovascular stenting of symptomatic high-grade
      innominate artery stenosis: technique and follow-up.
AB  - BACKGROUND AND PURPOSE: Angioplasty and stenting of the IA have been reported
      with high technical and clinical success rates, low complication rates and good
      mid-term patency rates. Different antegrade or retrograde endovascular catheter
      based approaches and combinations with surgical exposure of the CCA are used. The
      purpose of this study was to determine safety, efficacy and mid-term clinical and
      radiological outcome of the stent-assisted treatment of atherosclerotic stenotic
      disease of the IA with special focus on the different technical approaches.
      MATERIALS AND METHODS: Between 1996 and 2008, 18 patients (12 men, 6 women) with
      symptomatic high-grade stenosis (>80%) of the IA were treated with endovascular
      stent placement. Their mean age was 60.4 years (range, 48-78 years). Mean
      angiographic and clinical follow-up was 2.7 years (range, 0.3-9.1 years).
      Clinical follow-up was performed by using the mRS at hospital discharge, routine
      follow-up controls, and a questionnaire. In 11 patients, a percutaneous approach
      was used. In 7 patients, the lesions were accessed retrogradely through a
      cervical cut-down with common carotid arteriotomy. In 2 patients, a simultaneous
      ipsilateral carotid endarterectomy was performed. RESULTS: In all patients,
      primary stent placement was performed. There were 2 procedure-related transient
      complications (11.1%) due to cerebral embolism without permanent morbidity or
      mortality. During the follow-up, all patients showed improvement of the
      preprocedural symptoms. At the latest clinical follow-up (mean, 2.7 years), all
      patients showed an excellent or good outcome (mRS, 0 or 1). In 2 patients
      (11.1%), a secondary stent placement was needed due to a significant symptomatic
      in-stent stenosis. CONCLUSIONS: Percutaneous and open retrograde stenting of high
      grade stenosis of the IA is a viable less invasive alternatives to open bypass
      surgery with good midterm clinical results and patency rates.

PMID- 21852375
TI  - Impact of methodologic choice for automatic detection of different aspects of
      brain atrophy by using temporal lobe epilepsy as a model.
AB  - BACKGROUND AND PURPOSE: VBM, DBM, and cortical thickness measurement techniques
      are commonly used automated methods to detect structural brain changes based on
      MR imaging. The goal of this study was to demonstrate the pathology detected by
      the 3 methods and to provide guidance as to which method to choose for specific
      research questions. This goal was accomplished by 1) identifying structural
      abnormalities associated with TLE with (TLE-mts) and without (TLE-no) hippocampal
      sclerosis, which are known to be associated with different types of brain
      atrophy, by using these 3 methods; and 2) determining the aspect of the disease
      pathology identified by each method. MATERIALS AND METHODS: T1-weighted MR images
      were acquired for 15 TLE-mts patients, 14 TLE-no patients, and 33 controls on a
      high-field 4T scanner. Optimized VBM was carried out by using SPM software, DBM
      was performed by using a fluid-flow registration algorithm, and cortical
      thickness was analyzed by using FS-CT. RESULTS: In TLE-mts, the most pronounced
      volume losses were identified in the ipsilateral hippocampus and mesial temporal
      region, bilateral thalamus, and cerebellum, by using SPM-VBM and DBM. In TLE-no,
      the most widespread changes were cortical and identified by using FS-CT,
      affecting the bilateral temporal lobes, insula, and frontal and occipital lobes.
      DBM revealed 2 clusters of reduced volume complementing FS-CT analysis. SPM-VBM
      did not show any significant volume losses in TLE-no. CONCLUSIONS: These results
      demonstrate that the 3 methods detect different aspects of brain atrophy and that
      the choice of the method should be guided by the suspected pathology of the
      disease.

PMID- 21852377
TI  - Feasibility of flat panel angiographic CT after intravenous contrast agent
      application in the postoperative evaluation of patients with clipped aneurysms.
AB  - BACKGROUND AND PURPOSE: Important findings, such as aneurysm remnants or major
      arterial occlusion, can be detected on intra- or postoperative angiography after
      surgical clipping of intracranial aneurysms. The purpose of this study was to
      evaluate the feasibility of IV-ACT for the postoperative detection of residual
      aneurysms and parent vessel patency compared with IA-DSA, which was selected as
      the standard reference method. MATERIALS AND METHODS: Twenty-two patients with 27
      aneurysms treated by surgical clipping were examined by using both IA-DSA and IV
      ACT. Both diagnostic procedures were performed on an FPD-equipped angiography
      system. Postprocessing of IV-ACT acquisitions was performed on a dedicated
      workstation producing multiplanar reformations and maximum intensity projections
      of the clip region and other intracranial arteries. Three interventional
      neuroradiologists independently evaluated both procedures. RESULTS: A residual
      aneurysm was delineated in 10 cases with IA-DSA. Sufficient opacification of the
      intracranial vessels was assigned in 26 IV-ACT cases. Due to metal artifacts, IV
      ACT images were tagged as "not diagnostic" on 8 occasions. In the other 19
      aneurysms, a residual aneurysm was delineated in 6 cases-all 6 being true
      positive compared with IA-DSA-and was excluded in the remaining 13 cases-all true
      negative. Even small aneurysm remnants with a diameter of 1.5 mm were detected
      with IV-ACT. CONCLUSIONS: Currently IV-ACT cannot be recommended as a routine
      tool for postoperative evaluation of clipped aneurysms due to metal artifacts in
      30% of the examinations. These artifacts appear with multiple normal-sized or
      large clips. In patients with single or multiple small clips, IV-ACT can reliably
      show aneurysm remnants.

PMID- 21852378
TI  - Comparison of 2-year angiographic outcomes of stent- and nonstent-assisted coil
      embolization in unruptured aneurysms with an unfavorable configuration for
      coiling.
AB  - BACKGROUND AND PURPOSE: Stents are known to have hemodynamic and biologic effects
      in addition to their mechanical scaffold effect. To determine whether stents
      affect long-term outcomes after coiling of unruptured aneurysms, we compared
      angiographic outcomes at 2 years postembolization for stent- and nonstent
      assisted coiled unruptured aneurysms. MATERIALS AND METHODS: Stent-assisted
      coiling was used in unruptured aneurysms unfavorable for simple coiling (neck
      size >4 mm and dome-to-neck ratio <1.5) in our practice. Therefore, 126 coiled
      unruptured aneurysms in total (40 [31.7%] stent group and 86 [68.3%] nonstent
      group) with these conditions were selected for this study. The nonstent group
      aneurysms were treated with multiple microcatheter technique (53 cases) or
      balloon-assisted technique (33 cases). Self-expandable stents were used for
      coiling in stent group aneurysms. No significant difference in aneurysmal
      characteristics (aneurysm type [sidewall/bifurcation], diameter, neck size, and
      dome-to-neck ratio) or angiographic outcome at embolization (packing attenuation,
      obliteration grade, and contrast filling) were observed between the 2 study
      groups. RESULTS: At 2-year follow-up visits, rates of progressive occlusion
      (stent group, 17/40 [42.5%] versus nonstent group, 34/86 [39.5%]) and
      recanalization (7/40 [17.5%] versus 18/86 [21.0%]) did not show a statistically
      significant difference between the 2 groups (P = .895). CONCLUSIONS: The present
      study did not show that additional hemodynamic and biologic effects of stents
      designed for neck remodeling were enough to enhance progressive occlusion and
      prevent the recanalization of unruptured aneurysms. Our finding suggests that
      stent placement provides no better long-term angiographic outcomes for unruptured
      aneurysms with an unfavorable configuration for coiling.

PMID- 21852379
TI  - Spinal arteriovenous fistulas of the filum terminale.
AB  - The filum terminale is an anatomic structure at the end of the spinal cord. Only
      a few cases of AVFs of the filum terminale have been reported. These AVFs usually
      consist of a single communication between the anterior spinal artery and a single
      draining vein. We retrospectively analyzed the clinical and radiologic features
      and treatment of 4 patients with spinal AVFs of the filum terminale. Clinical
      manifestations and MR images are similar to those of spinal dural AVFs. All
      patients underwent surgical or endovascular treatment, resulting in complete
      occlusion. Clinical outcomes were good to excellent in all patients.

PMID- 21852380
TI  - Oncogene AEG-1 promotes glioma-induced neurodegeneration by increasing glutamate
      excitotoxicity.
AB  - Aggressive tumor growth, diffuse tissue invasion, and neurodegeneration are
      hallmarks of malignant glioma. Although glutamate excitotoxicity is considered to
      play a key role in glioma-induced neurodegeneration, the mechanism(s) controlling
      this process is poorly understood. Astrocyte elevated gene-1 (AEG-1) is an
      oncogene that is overexpressed in several types of human cancers, including more
      than 90% of brain tumors. In addition, AEG-1 promotes gliomagenesis, particularly
      in the context of tumor growth and invasion, 2 primary characteristics of glioma.
      In the present study, we investigated the contribution of AEG-1 to glioma-induced
      neurodegeneration. Pearson correlation coefficient analysis in normal brain
      tissues and samples from glioma patients indicated a strong negative correlation
      between expression of AEG-1 and a primary glutamate transporter of astrocytes
      EAAT2. Gain- and loss-of-function studies in normal primary human fetal
      astrocytes and T98G glioblastoma multiforme cells revealed that AEG-1 repressed
      EAAT2 expression at a transcriptional level by inducing YY1 activity to inhibit
      CBP function as a coactivator on the EAAT2 promoter. In addition, AEG-1-mediated
      EAAT2 repression caused a reduction of glutamate uptake by glial cells, resulting
      in induction of neuronal cell death. These findings were also confirmed in
      samples from glioma patients showing that AEG-1 expression negatively correlated
      with NeuN expression. Taken together, our findings suggest that AEG-1 contributes
      to glioma-induced neurodegeneration, a hallmark of this fatal tumor, through
      regulation of EAAT2 expression.

PMID- 21852381
TI  - MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer
      cells.
AB  - Cancer pathogenesis is restricted by stresses that compromise cell division and
      survival. In this study, we identify miR-708, a little studied member of a set of
      microRNAs that have been implicated in stress control, as an important tumor
      suppressor in renal cell carcinoma (RCC). miR-708 expression was attenuated
      widely in human RCC specimens. Restoration of miR-708 expression in RCC cell
      lines decreased cell growth, clonability, invasion, and migration and elicited a
      dramatic increase in apoptosis. Moreover, intratumoral delivery of miR-708 was
      sufficient to trigger in vivo regression of established tumors in murine
      xenograft models of human RCC. Investigation of the targets of miR-708 identified
      the inhibitor of apoptosis protein survivin as important. siRNA-mediated
      knockdown of survivin partially phenocopied miR-708 overexpression suggesting
      that the proapoptotic role of miR-708 may be mediated primarily through survivin
      regulation. Additionally, we identified the E-cadherin regulators ZEB2 and BMI1
      as likely miR-708 targets. Taken together, our findings define a major tumor
      suppressive role for miR-708, which may offer an attractive new target for
      prognostic and therapeutic intervention in RCC.

PMID- 21852382
TI  - Haploinsufficiency in the prometastasis Kiss1 receptor Gpr54 delays breast tumor
      initiation, progression, and lung metastasis.
AB  - Activation of KISS1 receptor (KISS1R or GPR54) by its ligands (Kisspeptins)
      regulates a diverse function both in normal physiology and pathophysiology. In
      cancer, KISS1R has been implicated in tumor angiogenesis and metastasis, but a
      broader evaluation of KISS1R in tumorigenesis and tumor progression is yet to be
      conducted. In this study, we used mouse models of Kiss1r gene knockout and mouse
      mammary tumor virus-polyoma virus middle T antigen (MMTV-PyMT)-induced breast
      cancer to conduct such an evaluation. Kiss1r heterozygosity in MMTV-PyMT mice was
      sufficient to attenuate breast cancer initiation, growth, latency, multiplicity,
      and lung metastasis. To confirm these effects and assess possible contributions
      of endogenous ligands, we isolated primary tumor cells from PyMT/Kiss1r(+/+) and
      PyMT/Kiss1r(+/-) mice and compared their phenotypes by in vitro and in vivo
      assays. Kiss1r loss attenuated in vitro tumorigenic properties as well as tumor
      growth in vivo in immunocompromised NOD.SCID/NCr mice. Kiss1r activation in these
      cells, resulting from the addition of its ligand Kisspeptin-10, resulted in RhoA
      activation and RhoA-dependent gene expression through the Galphaq-p63RhoGEF
      signaling pathway. Anchorage-independent growth was tightly linked to dose
      dependent regulation of RhoA by Kiss1r. In support of these results, siRNA
      mediated knockdown of KISS1R or inactivation of RhoA in human MCF10A breast
      epithelial cells overexpressing H-RasV12 was sufficient to reduce Ras-induced
      anchorage-independent growth. In summary, we concluded that Kiss1r attenuation
      was sufficient to delay breast tumor initiation, progression, and metastasis
      through inhibitory effects on the downstream Galphaq-p63RhoGEF-RhoA signaling
      pathway.

PMID- 21852384
TI  - A mutation threshold distinguishes the antitumorigenic effects of the
      mitochondrial gene MTND1, an oncojanus function.
AB  - The oncogenic versus suppressor roles of mitochondrial genes have long been
      debated. Peculiar features of mitochondrial genetics such as hetero/homoplasmy
      and mutation threshold are seldom taken into account in this debate.
      Mitochondrial DNA (mtDNA) mutations generally have been claimed to be
      protumorigenic, but they are also hallmarks of mostly benign oncocytic tumors
      wherein they help reduce adaptation to hypoxia by destabilizing hypoxia-inducible
      factor-1alpha (HIF1alpha). To determine the influence of a disassembling mtDNA
      mutation and its hetero/homoplasmy on tumorigenic and metastatic potential, we
      injected mice with tumor cells harboring different loads of the gene MTND1
      m.3571insC. Cell cultures obtained from tumor xenografts were then analyzed to
      correlate energetic competence, apoptosis, alpha-ketoglutarate (alpha
      KG)/succinate (SA) ratio, and HIF1alpha stabilization with the mutation load. A
      threshold level for the antitumorigenic effect of MTND1 m.3571insC mutation was
      defined, above which tumor growth and invasiveness were reduced significantly.
      Notably, HIF1alpha destabilization and downregulation of HIF1alpha-dependent
      genes occurred in cells and tumors lacking complex I (CI), where there was an
      associated imbalance of alpha-KG/SA despite the presence of an actual hypoxic
      environment. These results strongly implicate mtDNA mutations as a cause of
      oncocytic transformation. Thus, the antitumorigenic and antimetastatic effects of
      high loads of MTND1 m.3571insC, following CI disassembly, define a novel
      threshold-regulated class of cancer genes. We suggest these genes be termed
      oncojanus genes to recognize their ability to contribute either oncogenic or
      suppressive functions in mitochondrial settings during tumorigenesis.

PMID- 21852383
TI  - ZNF668 functions as a tumor suppressor by regulating p53 stability and function
      in breast cancer.
AB  - Genome-wide sequencing studies in breast cancer have recently identified frequent
      mutations in the zinc finger protein 668 (ZNF668), the function of which is
      undefined. Here, we report that ZNF668 is a nucleolar protein that physically
      interacts with and regulates p53 and its negative regulator MDM2. Through MDM2
      binding, ZNF668 regulated autoubiquitination of MDM2 and its ability to mediate
      p53 ubiquitination and degradation. ZNF668 deficiency also impaired DNA damage
      induced stabilization of p53. RNA interference-mediated knockdown of ZNF668 was
      sufficient to transform normal mammary epithelial cells. ZNF668 effectively
      suppressed breast cancer cell proliferation in vitro and tumorigenicity in vivo.
      Taken together, our studies identify ZNF668 as a novel breast tumor suppressor
      gene that functions in regulating p53 stability.

PMID- 21852385
TI  - EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in
      cells sustaining DNA double-strand breaks.
AB  - The mechanisms by which inhibition of the epidermal growth factor receptor (EGFR)
      sensitizes non-small cell lung cancer (NSCLC) cells to ionizing radiation remain
      poorly understood. We set out to characterize the radiosensitizing effects of the
      tyrosine kinase inhibitor erlotinib and the monoclonal antibody cetuximab in
      NSCLC cells that contain wild-type p53. Unexpectedly, EGFR inhibition led to
      pronounced cellular senescence but not apoptosis of irradiated cells, both in
      vitro and in vivo. Senescence was completely dependent on wild-type p53 and
      associated with a reduction in cell number as well as impaired clonogenic
      radiation survival. Study of ten additional NSCLC cell lines revealed that
      senescence is a prominent mechanism of radiosensitization in 45% of cell lines
      and occurs not only in cells with wild-type p53 but also in cells with mutant
      p53, where it is associated with an induction of p16. Interestingly, senescence
      and radiosensitization were linked to an increase in residual radiation-induced
      DNA double-strand breaks irrespective of p53/p16 status. This effect of EGFR
      inhibition was at least partially mediated by disruption of the MEK-ERK pathway.
      Thus, our data indicate a common mechanism of radiosensitization by erlotinib or
      cetuximab across diverse genetic backgrounds. Our findings also suggest that
      assays that are able to capture the initial proliferative delay that is
      associated with senescence should be useful for screening large cell line panels
      to identify genomic biomarkers of EGFR inhibitor-mediated radiosensitization.

PMID- 21852386
TI  - Early detection of tumor cells by innate immune cells leads to T(reg) recruitment
      through CCL22 production by tumor cells.
AB  - In breast carcinomas, patient survival seems to be negatively affected by the
      recruitment of regulatory T cells (T(reg)) within lymphoid aggregates by CCL22.
      However, the mechanisms underpinning this process, which may be of broader
      significance in solid tumors, have yet to be described. In this study, we
      determined how CCL22 production is controlled in tumor cells. In human breast
      carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly
      increased in response to inflammatory signals [TNF-alpha, IFN-gamma, and
      interleukin (IL)-1beta], contrasting with CCL17. Primary breast tumors and
      CD45(+) infiltrating immune cells appeared to cooperate in driving CCL22
      secretion, as shown clearly in cocultures of breast tumor cell lines and
      peripheral blood mononuclear cells (PBMC) or their supernatants. We determined
      that monocyte-derived IL-1beta and TNF-alpha are key players as monocyte
      depletion or neutralization of these cytokines attenuated secretion of CCL22.
      However, when purified monocytes were used, exogenous human IFN-gamma was also
      required to generate this response suggesting a role for IFN-gamma-producing
      cells within PBMCs. In this setting, we found that human IFN-gamma could be
      replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells
      or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken
      together, our results show a dialogue between NK and tumor cells leading to IFN
      gamma secretion, which in turn associates with monocyte-derived IL-1beta and TNF
      alpha to drive production of CCL22 by tumor cells and subsequent recruitment of
      T(reg). As one validation of this conclusion in primary breast tumors, we showed
      that NK cells and macrophages tend to colocalize within tumors. In summary, our
      findings suggest that at early times during tumorigenesis, the detection of tumor
      cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22
      secretion that recruits T(reg) to evade this early antitumor immune response.

PMID- 21852387
TI  - High-dose antiangiogenic therapy for glioblastoma: less may be more?
AB  - Targeting angiogenesis in glioblastoma rapidly reduces vascular permeability and
      contrast enhancement on MRI and prolongs progression-free survival. The long-term
      efficacy of bevacizumab and other antiangiogenic agents is limited, however,
      because of the rapid development of resistance. Alternative dosing approaches may
      be one mechanism of prolonging therapeutic efficacy.

PMID- 21852388
TI  - High-throughput semiquantitative analysis of insertional mutations in
      heterogeneous tumors.
AB  - Retroviral and transposon-based insertional mutagenesis (IM) screens are widely
      used for cancer gene discovery in mice. Exploiting the full potential of IM
      screens requires methods for high-throughput sequencing and mapping of transposon
      and retroviral insertion sites. Current protocols are based on ligation-mediated
      PCR amplification of junction fragments from restriction endonuclease-digested
      genomic DNA, resulting in amplification biases due to uneven genomic distribution
      of restriction enzyme recognition sites. Consequently, sequence coverage cannot
      be used to assess the clonality of individual insertions. We have developed a
      novel method, called shear-splink, for the semiquantitative high-throughput
      analysis of insertional mutations. Shear-splink employs random fragmentation of
      genomic DNA, which reduces unwanted amplification biases. Additionally, shear
      splink enables us to assess clonality of individual insertions by determining the
      number of unique ligation points (LPs) between the adapter and genomic DNA. This
      parameter serves as a semiquantitative measure of the relative clonality of
      individual insertions within heterogeneous tumors. Mixing experiments with clonal
      cell lines derived from mouse mammary tumor virus (MMTV)-induced tumors showed
      that shear-splink enables the semiquantitative assessment of the clonality of
      MMTV insertions. Further, shear-splink analysis of 16 MMTV- and 127 Sleeping
      Beauty (SB)-induced tumors showed enrichment for cancer-relevant insertions by
      exclusion of irrelevant background insertions marked by single LPs, thereby
      facilitating the discovery of candidate cancer genes. To fully exploit the use of
      the shear-splink method, we set up the Insertional Mutagenesis Database (iMDB),
      offering a publicly available web-based application to analyze both retroviral-
      and transposon-based insertional mutagenesis data.

PMID- 21852389
TI  - The effects of betahistine in addition to epley maneuver in posterior canal
      benign paroxysmal positional vertigo.
AB  - OBJECTIVE: The purpose of this study is to evaluate the effects of betahistine in
      addition to Epley maneuver on the quality of life of patients with posterior
      semicircular canal benign paroxysmal positional vertigo (BPPV) of the
      canalithiasis type. STUDY DESIGN: Double-blind, randomized, controlled clinical
      trial. SETTING: Academic university hospital. SUBJECTS AND METHODS: Seventy-two
      patients were enrolled in the study. The first group was treated with Epley
      maneuver only. The second group received placebo drug 2 times daily for 1 week in
      addition to Epley maneuver, and the third group received 24 mg betahistine 2
      times daily for 1 week in addition to Epley maneuver. The effectiveness of the
      treatments was assessed in each group as well as between them by analyzing and
      comparing data of 4 different vertigo symptom scales. RESULTS: Epley maneuver,
      alone or combined with betahistine or placebo, was found to be very effective
      with a primary success rate of 86.2%. The symptoms were significantly reduced in
      group 3 patients overall, and those patients younger or older than 50 years of
      age who had hypertension, with symptom onset <1 month, and with attack duration
      of less than a minute did significantly better with the combination of
      betahistine 48 mg daily. CONCLUSION: Betahistine in addition to Epley maneuver is
      more effective than Epley maneuver alone or combined with placebo with regard to
      improvement of symptoms in certain patients. However, future clinical studies
      covering more patients to investigate the benefit of medical treatments in
      addition to Epley maneuver are needed.

PMID- 21852390
TI  - Denosumab for bone diseases: translating bone biology into targeted therapy.
AB  - Signalling of receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL)
      through RANK is a critical pathway to regulate the differentiation and activity
      of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL
      activity has been demonstrated in diseases characterised by excessive bone loss
      such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The
      development and approval of denosumab, a fully MAB against RANKL, has heralded a
      new era in the treatment of bone diseases by providing a potent, targeted and
      reversible inhibitor of bone resorption. This article summarises the molecular
      and cellular biology of the RANKL/RANK system and critically reviews preclinical
      and clinical studies that have established denosumab as a promising novel therapy
      for metabolic and malignant bone diseases. We will discuss the potential
      indications for denosumab along with a critical review of safety and analyse its
      potential within the concert of established therapies.

PMID- 21852391
TI  - Hypogonadism as a risk factor for cardiovascular mortality in men: a meta
      analytic study.
AB  - OBJECTIVE: To verify whether hypogonadism represents a risk factor for
      cardiovascular (CV) morbidity and mortality and to verify whether testosterone
      replacement therapy (TRT) improves CV parameters in subjects with known CV
      diseases (CVDs). DESIGN: Meta-analysis. METHODS: An extensive Medline search was
      performed using the following words 'testosterone, CVD, and males'. The search
      was restricted to data from January 1, 1969, up to January 1, 2011. RESULTS: Of
      the 1178 retrieved articles, 70 were included in the study. Among cross-sectional
      studies, patients with CVD have significantly lower testosterone and higher 17
      beta estradiol (E(2)) levels. Conversely, no difference was observed for DHEAS.
      The association between low testosterone and high E(2) levels with CVD was
      confirmed in a logistic regression model, after adjusting for age and body mass
      index (hazard ratio (HR)=0.763 (0.744-0.783) and HR=1.015 (1.014-1.017),
      respectively, for each increment of total testosterone and E(2) levels; both
      P<0.0001). Longitudinal studies showed that baseline testosterone level was
      significantly lower among patients with incident overall- and CV-related
      mortality, in comparison with controls. Conversely, we did not observe any
      difference in the baseline testosterone and E(2) levels between case and controls
      for incident CVD. Finally, TRT was positively associated with a significant
      increase in treadmill test duration and time to 1 mm ST segment depression.
      CONCLUSIONS: Lower testosterone and higher E(2) levels correlate with increased
      risk of CVD and CV mortality. TRT in hypogonadism moderates metabolic components
      associated with CV risk. Whether low testosterone is just an association with CV
      risk, or an actual cause-effect relationship, awaits further studies.

PMID- 21852392
TI  - Standardization and diversification of copy number microarray testing for
      clinical diagnostics--implications of the cross-platform/algorithm study on
      clinical diagnostic chromosomal microarray analysis.

PMID- 21852393
TI  - Cell cycle-regulated multi-site phosphorylation of Neurogenin 2 coordinates cell
      cycling with differentiation during neurogenesis.
AB  - During development of the central nervous system, the transition from progenitor
      maintenance to differentiation is directly triggered by a lengthening of the cell
      cycle that occurs as development progresses. However, the mechanistic basis of
      this regulation is unknown. The proneural transcription factor Neurogenin 2
      (Ngn2) acts as a master regulator of neuronal differentiation. Here, we
      demonstrate that Ngn2 is phosphorylated on multiple serine-proline sites in
      response to rising cyclin-dependent kinase (cdk) levels. This multi-site
      phosphorylation results in quantitative inhibition of the ability of Ngn2 to
      induce neurogenesis in vivo and in vitro. Mechanistically, multi-site
      phosphorylation inhibits binding of Ngn2 to E box DNA, and inhibition of DNA
      binding depends on the number of phosphorylation sites available, quantitatively
      controlling promoter occupancy in a rheostat-like manner. Neuronal
      differentiation driven by a mutant of Ngn2 that cannot be phosphorylated by cdks
      is no longer inhibited by elevated cdk kinase levels. Additionally, phosphomutant
      Ngn2-driven neuronal differentiation shows a reduced requirement for the presence
      of cdk inhibitors. From these results, we propose a model whereby multi-site cdk
      dependent phosphorylation of Ngn2 interprets cdk levels to control neuronal
      differentiation in response to cell cycle lengthening during development.

PMID- 21852394
TI  - Distinct and mutually inhibitory binding by two divergent beta-catenins
      coordinates TCF levels and activity in C. elegans.
AB  - Wnt target gene activation in C. elegans requires simultaneous elevation of beta
      catenin/SYS-1 and reduction of TCF/POP-1 nuclear levels within the same signal
      responsive cell. SYS-1 binds to the conserved N-terminal beta-catenin-binding
      domain (CBD) of POP-1 and functions as a transcriptional co-activator.
      Phosphorylation of POP-1 by LIT-1, the C. elegans Nemo-like kinase homolog,
      promotes POP-1 nuclear export and is the main mechanism by which POP-1 nuclear
      levels are lowered. We present a mechanism whereby SYS-1 and POP-1 nuclear levels
      are regulated in opposite directions, despite the fact that the two proteins
      physically interact. We show that the C terminus of POP-1 is essential for LIT-1
      phosphorylation and is specifically bound by the diverged beta-catenin WRM-1. WRM
      1 does not bind to the CBD of POP-1, nor does SYS-1 bind to the C-terminal
      domain. Furthermore, binding of WRM-1 to the POP-1 C terminus is mutually
      inhibitory with SYS-1 binding at the CBD. Computer modeling provides a structural
      explanation for the specificity in WRM-1 and SYS-1 binding to POP-1. Finally, WRM
      1 exhibits two independent and distinct molecular functions that are novel for
      beta-catenins: WRM-1 serves both as the substrate-binding subunit and an obligate
      regulatory subunit for the LIT-1 kinase. Mutual inhibitory binding would result
      in two populations of POP-1: one bound by WRM-1 that is LIT-1 phosphorylated and
      exported from the nucleus, and another, bound by SYS-1, that remains in the
      nucleus and transcriptionally activates Wnt target genes. These studies could
      provide novel insights into cancers arising from aberrant Wnt activation.

PMID- 21852395
TI  - The Hedgehog-induced Smoothened conformational switch assembles a signaling
      complex that activates Fused by promoting its dimerization and phosphorylation.
AB  - Hedgehog (Hh) transduces signal by regulating the subcellular localization and
      conformational state of the GPCR-like protein Smoothened (Smo) but how Smo relays
      the signal to cytoplasmic signaling components remains poorly understood. Here,
      we show that Hh-induced Smo conformational change recruits Costal2 (Cos2)/Fused
      (Fu) and promotes Fu kinase domain dimerization. We find that induced
      dimerization through the Fu kinase domain activates Fu by inducing multi-site
      phosphorylation of its activation loop (AL) and phospho-mimetic mutations of AL
      activate the Hh pathway. Interestingly, we observe that graded Hh signals
      progressively increase Fu kinase domain dimerization and AL phosphorylation,
      suggesting that Hh activates Fu in a dose-dependent manner. Moreover, we find
      that activated Fu regulates Cubitus interruptus (Ci) by both promoting its
      transcriptional activator activity and inhibiting its proteolysis into a
      repressor form. We provide evidence that activated Fu exerts these regulations by
      interfering with the formation of Ci-Sufu and Ci-Cos2-kinase complexes that
      normally inhibit Ci activity and promote its processing. Taken together, our
      results suggest that Hh-induced Smo conformational change facilitates the
      assembly of active Smo-Cos2-Fu signaling complexes that promote Fu kinase domain
      dimerization, phosphorylation and activation, and that Fu regulates both the
      activator and repressor forms of Ci.

PMID- 21852396
TI  - HNF4A is essential for specification of hepatic progenitors from human
      pluripotent stem cells.
AB  - The availability of pluripotent stem cells offers the possibility of using such
      cells to model hepatic disease and development. With this in mind, we previously
      established a protocol that facilitates the differentiation of both human
      embryonic stem cells and induced pluripotent stem cells into cells that share
      many characteristics with hepatocytes. The use of highly defined culture
      conditions and the avoidance of feeder cells or embryoid bodies allowed
      synchronous and reproducible differentiation to occur. The differentiation
      towards a hepatocyte-like fate appeared to recapitulate many of the developmental
      stages normally associated with the formation of hepatocytes in vivo. In the
      current study, we addressed the feasibility of using human pluripotent stem cells
      to probe the molecular mechanisms underlying human hepatocyte differentiation. We
      demonstrate (1) that human embryonic stem cells express a number of mRNAs that
      characterize each stage in the differentiation process, (2) that gene expression
      can be efficiently depleted throughout the differentiation time course using
      shRNAs expressed from lentiviruses and (3) that the nuclear hormone receptor
      HNF4A is essential for specification of human hepatic progenitor cells by
      establishing the expression of the network of transcription factors that controls
      the onset of hepatocyte cell fate.

PMID- 21852397
TI  - The cytoplasmic domain of neuropilin 1 is dispensable for angiogenesis, but
      promotes the spatial separation of retinal arteries and veins.
AB  - Neuropilin 1 (NRP1) is a transmembrane glycoprotein that is essential for blood
      vessel development in vertebrates. Best known for its ability to bind members of
      the vascular endothelial growth factor (VEGF) and class 3 semaphorin families
      through its extracellular domain, it also has a highly conserved cytoplasmic
      domain, which terminates in a SEA motif that binds the PDZ protein
      synectin/GIPC1/NIP. Previous studies in zebrafish embryos and tissue culture
      models raised the possibility that the SEA motif of NRP1 is essential for
      angiogenesis. Here, we describe the generation of mice that express a form of
      NRP1 that lacks the cytoplasmic domain and, therefore, the SEA motif
      (Nrp1(cyto)(Delta)(/)(Delta) mice). Our analysis of pre- and perinatal vascular
      development revealed that vasculogenesis and angiogenesis proceed normally in
      these mutants, demonstrating that the membrane-anchored extracellular domain is
      sufficient for vessel growth. By contrast, the NRP1 cytoplasmic domain is
      required for normal arteriovenous patterning, because arteries and veins crossed
      each other at an abnormally high frequency in the Nrp1(cyto)(Delta)(/)(Delta)
      retina, as previously reported for mice with haploinsufficient expression of VEGF
      in neural progenitors. At crossing sites, the artery was positioned anteriorly to
      the vein, and both vessels were embedded in a shared collagen sleeve. In human
      eyes, similar arteriovenous crossings are risk factors for branch retinal vein
      occlusion (BRVO), an eye disease in which compression of the vein by the artery
      disrupts retinal blood flow, causing local tissue hypoxia and impairing vision.
      Nrp1(cyto)(Delta)(/)(Delta) mice may therefore provide a suitable genetic model
      to study the aetiology of BRVO.

PMID- 21852399
TI  - Gcm/Glide-dependent conversion into glia depends on neural stem cell age, but not
      on division, triggering a chromatin signature that is conserved in vertebrate
      glia.
AB  - Neurons and glia differentiate from multipotent precursors called neural stem
      cells (NSCs), upon the activation of specific transcription factors. In vitro, it
      has been shown that NSCs display very plastic features; however, one of the major
      challenges is to understand the bases of lineage restriction and NSC plasticity
      in vivo, at the cellular level. We show here that overexpression of the Gcm
      transcription factor, which controls the glial versus neuronal fate choice, fully
      and efficiently converts Drosophila NSCs towards the glial fate via an
      intermediate state. Gcm acts in a dose-dependent and autonomous manner by
      concomitantly repressing the endogenous program and inducing the glial program in
      the NSC. Most NSCs divide several times to build the embryonic nervous system and
      eventually enter quiescence: strikingly, the gliogenic potential of Gcm decreases
      with time and quiescent NSCs are resistant to fate conversion. Together with the
      fact that Gcm is able to convert mutant NSCs that cannot divide, this indicates
      that plasticity depends on temporal cues rather than on the mitotic potential.
      Finally, NSC plasticity involves specific chromatin modifications. The endogenous
      glial cells, as well as those induced by Gcm overexpression display low levels of
      histone 3 lysine 9 acetylation (H3K9ac) and Drosophila CREB-binding protein
      (dCBP) Histone Acetyl-Transferase (HAT). Moreover, we show that dCBP targets the
      H3K9 residue and that high levels of dCBP HAT disrupt gliogenesis. Thus, glial
      differentiation needs low levels of histone acetylation, a feature shared by
      vertebrate glia, calling for an epigenetic pathway conserved in evolution.

PMID- 21852398
TI  - Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in
      mesenchymal-to-epithelial transition of nephron stem cells.
AB  - The primary excretory organ in vertebrates is the kidney, which is responsible
      for blood filtration, solute homeostasis and pH balance. These functions are
      carried out by specialized epithelial cells organized into tubules called
      nephrons. Each of these cell types arise during embryonic development from a
      mesenchymal stem cell pool through a process of mesenchymal-to-epithelial
      transition (MET) that requires sequential action of specific Wnt signals.
      Induction by Wnt9b directs cells to exit the stem cell niche and express Wnt4,
      which is both necessary and sufficient for the formation of epithelia. Without
      either factor, MET fails, nephrons do not form and newborn mice die owing to
      kidney failure. Ectopic Notch activation in stem cells induces mass
      differentiation and exhaustion of the stem cell pool. To investigate whether this
      reflected an interaction between Notch and Wnt, we employed a novel gene
      manipulation strategy in cultured embryonic kidneys. We show that Notch
      activation is capable of inducing MET in the absence of both Wnt4 and Wnt9b.
      Following MET, the presence of Notch directs cells primarily to the proximal
      tubule fate. Only nephron stem cells have the ability to undergo MET in response
      to Wnt or Notch, as activation in the closely related stromal mesenchyme has no
      inductive effect. These data demonstrate that stem cells for renal epithelia are
      uniquely poised to undergo MET, and that Notch activation can replace key
      inductive Wnt signals in this process. After MET, Notch provides an instructive
      signal directing cells towards the proximal tubule lineage at the expense of
      other renal epithelial fates.

PMID- 21852400
TI  - LGN-dependent orientation of cell divisions in the dermomyotome controls lineage
      segregation into muscle and dermis.
AB  - The plane of cell divisions is pivotal for differential fate acquisition.
      Dermomyotome development provides an excellent system with which to investigate
      the link between these processes. In the central sheet of the early dermomyotome,
      single epithelial cells divide with a planar orientation. Here, we report that in
      the avian embryo, in addition to self-renewing, a subset of progenitors
      translocates into the myotome where they generate differentiated myocytes. By
      contrast, in the late epithelium, individual progenitors divide perpendicularly
      to produce both mitotic myoblasts and dermis. To examine whether spindle
      orientations influence fate segregation, early planar divisions were randomized
      and/or shifted to a perpendicular orientation by interfering with LGN function or
      by overexpressing inscuteable. Clones derived from single transfected cells
      exhibited an enhanced proportion of mixed dermomyotome/myotome progeny at the
      expense of 'like' daughter cells in either domain. Loss of LGN or Galphai1
      function in the late epithelium randomized otherwise perpendicular mitoses and
      favored muscle development at the expense of dermis. Hence, LGN-dependent early
      planar divisions are required for the proper allocation of progenitors into
      either dermomyotome or myotome, whereas late perpendicular divisions are
      necessary for the normal balance between muscle and dermis production.

PMID- 21852401
TI  - Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell
      proliferation and fate.
AB  - Studies of the olfactory epithelium model system have demonstrated that
      production of neurons is regulated by negative feedback. Previously, we showed
      that a locally produced signal, the TGFbeta superfamily ligand GDF11, regulates
      the genesis of olfactory receptor neurons by inhibiting proliferation of the
      immediate neuronal precursors (INPs) that give rise to them. GDF11 is antagonized
      by follistatin (FST), which is also produced locally. Here, we show that Fst(-/-)
      mice exhibit dramatically decreased neurogenesis, a phenotype that can only be
      partially explained by increased GDF11 activity. Instead, a second FST-binding
      factor, activin betaB (ACTbetaB), inhibits neurogenesis by a distinct mechanism:
      whereas GDF11 inhibits expansion of INPs, ACTbetaB inhibits expansion of stem and
      early progenitor cells. We present data supporting the concept that these latter
      cells, previously considered two distinct types, constitute a dynamic
      stem/progenitor population in which individual cells alternate expression of Sox2
      and/or Ascl1. In addition, we demonstrate that interplay between ACTbetaB and
      GDF11 determines whether stem/progenitor cells adopt a glial versus neuronal
      fate. Altogether, the data indicate that the transition between stem cells and
      committed progenitors is neither sharp nor irreversible and that GDF11, ACTbetaB
      and FST are crucial components of a circuit that controls both total cell number
      and the ratio of neuronal versus glial cells in this system. Thus, our findings
      demonstrate a close connection between the signals involved in the control of
      tissue size and those that regulate the proportions of different cell types.

PMID- 21852403
TI  - Effects of acute sprint interval cycling and energy replacement on postprandial
      lipemia.
AB  - High postprandial blood triglyceride (TG) levels increase cardiovascular disease
      risk. Exercise interventions may be effective in reducing postprandial blood TG.
      The purpose of this study was to determine the effects of sprint interval cycling
      (SIC), with and without replacement of the energy deficit, on postprandial
      lipemia. In a repeated-measures crossover design, six men and six women
      participated in three trials, each taking place over 2 days. On the evening of
      the first day of each trial, the participants either did SIC without replacing
      the energy deficit (Ex-Def), did SIC and replaced the energy deficit (Ex-Bal), or
      did not exercise (control). SIC was performed on a cycle ergometer and involved
      four 30-s all-out sprints with 4-min active recovery. In the morning of day 2,
      responses to a high-fat meal were measured. Venous blood samples were collected
      in the fasted state and at 0, 30, 60, 120, and 180 min postprandial. There was a
      trend toward a reduction with treatment in fasting TG (P = 0.068), but no
      significant treatment effect for fasting insulin, glucose, nonesterified fatty
      acids, or betahydroxybutryrate (P > 0.05). The postprandial area under the curve
      (mmol.l(-1).3 h(-1)) TG response was significantly lower in Ex-Def (21%, P =
      0.006) and Ex-Bal (10%, P = 0.044) than in control, and significantly lower in Ex
      Def (12%, P = 0.032) than in Ex-Bal. There was no treatment effect (P > 0.05)
      observed for area under the curve responses of insulin, glucose, nonesterified
      fatty acids, or betahydroxybutryrate. SIC reduces postprandial lipemia, but the
      energy deficit alone does not fully explain the decrease observed.

PMID- 21852402
TI  - Fez function is required to maintain the size of the animal plate in the sea
      urchin embryo.
AB  - Partitioning ectoderm precisely into neurogenic and non-neurogenic regions is an
      essential step for neurogenesis of almost all bilaterian embryos. Although it is
      widely accepted that antagonism between BMP and its inhibitors primarily sets up
      the border between these two types of ectoderm, it is unclear how such
      extracellular, diffusible molecules create a sharp and precise border at the
      single-cell level. Here, we show that Fez, a zinc finger protein, functions as an
      intracellular factor attenuating BMP signaling specifically within the neurogenic
      region at the anterior end of sea urchin embryos, termed the animal plate. When
      Fez function is blocked, the size of this neurogenic ectoderm becomes smaller
      than normal. However, this reduction is rescued in Fez morphants simply by
      blocking BMP2/4 translation, indicating that Fez maintains the size of the animal
      plate by attenuating BMP2/4 function. Consistent with this, the gradient of BMP
      activity along the aboral side of the animal plate, as measured by pSmad1/5/8
      levels, drops significantly in cells expressing Fez and this steep decline
      requires Fez function. Our data reveal that this neurogenic ectoderm produces an
      intrinsic system that attenuates BMP signaling to ensure the establishment of a
      stable, well-defined neural territory, the animal plate.

PMID- 21852404
TI  - Microbubble detection following hyperbaric chamber dives using dual-frequency
      ultrasound.
AB  - Venous gas emboli (VGE) can be readily detected in the bloodstream using existing
      ultrasound methods. No method currently exists to detect decompression-induced
      microbubbles in tissue. We hypothesized that dual-frequency ultrasound (DFU)
      could detect these microbubbles. With DFU, microbubbles are driven with two
      frequencies: a lower "pump" (set to the resonant frequency of the desired bubble
      size) and a higher "image" frequency. A bubble of the resonant size emits the sum
      and difference of the two transmitted frequencies. For this study we used a pump
      frequency of 2.25 MHz and an image frequency of 5.0 MHz, which detects bubbles of
      roughly 1-10 MUm in diameter in a water tank. Four anesthetized swine were
      pressurized at 4.5 ATA for 2 h and decompressed over 5 min, inducing moderate to
      very severe VGE scores. Four sites on the thigh of each swine were monitored with
      DFU before and after the dives. A single mock dive was also performed. The number
      of sites returning signals consistent with microbubbles increased dramatically
      after the chamber dive (P < 0.01), but did not change with the mock dive. The
      increase in DFU signal after the chamber dive was sustained and present at
      multiple sites in multiple swine. This research shows for the first time that
      decompression-induced tissue microbubbles can be detected using DFU and that DFU
      could be used to monitor decompression-induced microbubbles at multiple sites on
      the body. Additionally, DFU could be used to track the time course of microbubble
      formation and growth during decompression stress.

PMID- 21852406
TI  - Atorvastatin treatment reduces exercise capacities in rats: involvement of
      mitochondrial impairments and oxidative stress.
AB  - Physical exercise exacerbates the cytotoxic effects of statins in skeletal
      muscle. Mitochondrial impairments may play an important role in the development
      of muscular symptoms following statin treatment. Our objective was to
      characterize mitochondrial function and reactive oxygen species (ROS) production
      in skeletal muscle after exhaustive exercise in atorvastatin-treated rats. The
      animals were divided into four groups: resting control (CONT; n = 8) and exercise
      rats (CONT+EXE; n = 8) as well as resting (ATO; n = 10) and exercise (ATO+EXE; n
      = 8) rats that were treated with atorvastatin (10 mg.kg(-1).day(-1) for 2 wk).
      Exhaustive exercise showed that the distance that was covered by treated animals
      was reduced (P < 0.05). Using dihydroethidium staining, we showed that the ROS
      level was increased by 60% in the plantaris muscle of ATO compared with CONT rats
      and was highly increased in ATO+EXE (226%) compared with that in CONT+EXE rats.
      The maximal mitochondrial respiration (V(max)) was decreased in ATO rats compared
      with that in CONT rats (P < 0.01). In CONT+EXE rats, V(max) significantly
      increased compared with those in CONT rats (P < 0.05). V(max) was significantly
      lower in ATO+EXE rats (-39%) compared with that in CONT+EXE rats (P < 0.001). The
      distance that was covered by rats significantly correlated with V(max) (r = 0.62,
      P < 0.01). The glycogen content was decreased in ATO, CONT+EXE, and ATO+EXE rats
      compared with that in CONT rats (P < 0.05). GLUT-4 mRNA expression was higher
      after exhaustive exercise in CONT+EXE rats compared with the other groups (P <
      0.05). Our results show that exhaustive exercise exacerbated metabolic
      perturbations and ROS production in skeletal muscle, which may reduce the
      exercise capacity and promote the muscular symptoms in sedentary atorvastatin
      treated animals.

PMID- 21852405
TI  - Arm exercise stress perfusion imaging predicts clinical outcome.
AB  - Treadmill exercise capacity in resting metabolic equivalents (METs) and stress
      hemodynamic, electrocardiographic (ECG), and myocardial perfusion imaging (MPI)
      responses are independently predictive of adverse clinical events. However,
      limited data exist for arm ergometer stress testing (AXT) in patients who cannot
      perform leg exercise because of lower extremity disabilities. We sought to
      determine the extent to which AXT METs, hemodynamic, ECG, and MPI responses to
      arm exercise add independent incremental value to demographic and clinical
      variables for prediction of all-cause mortality, myocardial infarction (MI), or
      late coronary revascularization, individually or as a composite. A prospective
      cohort of 186 patients aged 64 +/- 10 (SD) yr, unable to perform lower extremity
      exercise, underwent AXT MPI for clinical reasons between 1997 and 2002, and were
      followed for 62 +/- 23 mo, to an endpoint of death or 12/31/2006. Average annual
      rates were 5.4% for mortality, 2.2% for MI, 2.5% for late coronary
      revascularization, and 8.0% for combined events. After adjustment for age and
      clinical variables, AXT METs [P < 0.05; hazard ratio (HR) = 0.59; confidence
      interval (CI) = 0.35-0.84] and abnormal MPI (P < 0.01; HR = 2.48; CI = 2.15-2.81)
      were independently predictive of mortality. A positive AXT ECG (P < 0.05; HR =
      2.61; CI = 2.13-3.10) was predictive of MI. Death and MI combined were
      prognosticated by METs (P < 0.05; HR = 0.63; CI = 0.41-0.85), MPI (P < 0.05; HR =
      1.77; CI = 1.49-2.05), and a positive AXT ECG (P < 0.05; HR = 1.86; CI = 1.55
      2.17). In conclusion, for high risk older patients who cannot perform leg
      exercise because of lower extremity disabilities, AXT METs are as important as
      MPI for prediction of mortality alone and death and MI combined, and a positive
      AXT ECG prognosticates MI alone and death and MI combined.

PMID- 21852407
TI  - Noninvasive estimation of pharyngeal airway resistance and compliance in children
      based on volume-gated dynamic MRI and computational fluid dynamics.
AB  - Computational fluid dynamics (CFD) analysis was used to model the effect of
      collapsing airway geometry on internal pressure and velocity in the pharyngeal
      airway of three sedated children with obstructive sleep apnea syndrome (OSAS) and
      three control subjects. Model geometry was reconstructed from volume-gated
      magnetic resonance images during normal tidal breathing at 10 increments of tidal
      volume through the respiratory cycle. Each geometry was meshed with an
      unstructured grid and solved using a low-Reynolds number k-omega turbulence model
      driven by flow data averaged over 12 consecutive breathing cycles. Combining
      gated imaging with CFD modeling created a dynamic three-dimensional view of
      airway anatomy and mechanics, including the evolution of airway collapse and flow
      resistance and estimates of the local effective compliance. The upper airways of
      subjects with OSAS were generally much more compliant during tidal breathing.
      Compliance curves (pressure vs. cross-section area), derived for different
      locations along the airway, quantified local differences along the pharynx and
      between OSAS subjects. In one subject, the distal oropharynx was more compliant
      than the nasopharynx (1.028 vs. 0.450 mm(2)/Pa) and had a lower theoretical
      limiting flow rate, confirming the distal oropharynx as the flow-limiting segment
      of the airway in this subject. Another subject had a more compliant nasopharynx
      (0.053 mm(2)/Pa) during inspiration and apparent stiffening of the distal
      oropharynx (C = 0.0058 mm(2)/Pa), and the theoretical limiting flow rate
      indicated the nasopharynx as the flow-limiting segment. This new method may help
      to differentiate anatomical and functional factors in airway collapse.

PMID- 21852409
TI  - Understanding multi-organ pathology from insufficient exercise.

PMID- 21852408
TI  - Critical closing pressure during midazolam-induced sleep.
AB  - The critical closing pressure (Pcrit) is the airway pressure at which the airway
      collapses and reflects the anatomical contribution to the genesis of obstructive
      sleep apnea. Pcrit is usually determined during non-rapid eye movement sleep at
      night, but has been determined under midazolam sedation during the day in the
      absence of sleep stage monitoring. Indeed, little is known about the effects of
      midazolam on sleep architecture. Moreover, deeper sedation with midazolam can
      decrease upper airway muscle activity and increase collapsibility compared with
      natural sleep. Pcrit under sedation has not been systematically compared with the
      usual method performed during natural sleep. Therefore, this study aimed to test
      the hypothesis that Pcrit following low doses of midazolam during the day would
      be comparable to Pcrit measured during natural sleep in the same patient. Fifteen
      men (age 54 +/- 10 yr, body mass index 30 +/- 4 kg/m(2)) with obstructive sleep
      apnea underwent a baseline standard overnight polysomnogram (apnea-hypopnea index
      38 +/- 22 events/h, range: 8-66 events/h), and Pcrit was determined during
      natural sleep and following midazolam. Sleep induction was obtained with low
      doses of midazolam (2.4 mg, range 2.0-4.4 mg), and sleep architecture was
      comparable to natural sleep. Natural sleep and induced sleep Pcrit were similar (
      0.82 +/- -3.44 and -0.97 +/- 3.21 cmH(2)O, P = 0.663) and closely associated
      (intraclass correlation coefficient = 0.92; 95% confidence interval, 0.78-0.97, P
      < 0.001). Natural and midazolam-induced Pcrit correlated with obstructive sleep
      apnea severity, indicating that both Pcrit measures provided meaningful
      physiological information. Pcrit determined during the day with sleep induction
      is similar to natural overnight sleep and is a valid alternative approach in
      which to determine Pcrit.

PMID- 21852410
TI  - Massive weight loss-induced mechanical plasticity in obese gait.
AB  - We examined the hypothesis that metabolic surgery-induced massive weight loss
      causes mass-driven and behavioral adaptations in the kinematics and kinetics of
      obese gait. Gait analyses were performed at three time points over ~1 yr in
      initially morbidly obese (mass: 125.7 kg; body mass index: 43.2 kg/m(2)) but
      otherwise healthy adults. Ten obese adults lost 27.1% +/- 5.1 (34.0 +/- 9.4 kg)
      weight by the first follow-up at 7.0 mo (+/-0.7) and 6.5 +/- 4.2% (8.2 +/- 6.0
      kg) more by the second follow-up at 12.8 mo (+/-0.9), with a total weight loss of
      33.6 +/- 8.1% (42.2 +/- 14.1 kg; P = 0.001). Subjects walked at a self-selected
      and a standard 1.5 m/s speed at the three time points and were also compared with
      an age- and gender-matched comparison group at the second follow-up. Weight loss
      increased swing time, stride length, gait speed, hip range of motion, maximal
      knee flexion, and ankle plantarflexion. Weight loss of 27% led to 3.9% increase
      in gait speed. An additional 6.5% weight loss led to an additional 7.3% increase
      in gait speed. Sagittal plane normalized knee torque increased and absolute ankle
      and frontal plane knee torques decreased after weight loss. We conclude that
      large weight loss produced mechanical plasticity by modifying ankle and knee
      torques and gait behavior. There may be a weight loss threshold of 30 kg limiting
      changes in gait kinematics. Implications for exercise prescription are also
      discussed.

PMID- 21852411
TI  - Safety by design: effects of operating room floor marking on the position of
      surgical devices to promote clean air flow compliance and minimise infection
      risks.
AB  - OBJECTIVE: To evaluate the use of floor marking on the positioning of surgical
      devices within the clean air flow in an operating room (OR) to minimise infection
      risk. Laminar flow clean air systems are important in preventing infection in ORs
      but, for optimal results, surgical devices must be correctly positioned. METHODS:
      The authors evaluated floor marking in four ORs at an eye hospital using time
      series analysis. Through observations during 829 surgeries over a 20-month
      period, the positions of surgical devices were determined. Eight semistructured
      interviews with surgical staff were conducted to assess user experiences and team
      dynamics. RESULTS: Before marking, the instrument table was positioned completely
      within the laminar flow in only 6.1% of the cases. This increased to 36.1% and
      finally 53.8%. Mayo stands were increasingly positioned within the laminar flow:
      from 74.2% to 84.7%. The surgical lamp decreasingly obstructed flow: from 41.8%
      to 28.7%. At T3 (20 months), however, in 48.6% of the applicable cases the lamp
      was positioned in the flow again. Discussions and site visits between airside
      operators and surgical staff resulted in increasing awareness of specific risk
      areas in the OR. CONCLUSIONS: OR floor markings facilitated and stimulated safety
      awareness and resulted in significantly increased compliance with the positioning
      of surgical devices in the clean air flow. Safety and quality approaches in
      hospital care, therefore, should include a human factors approach that focuses on
      system design in addition to teaching clinical and non-technical skills.

PMID- 21852413
TI  - Roadmap to a tobacco epidemic: transnational tobacco companies invade Indonesia.
AB  - BACKGROUND: Indonesia is the world's fifth largest cigarette market in the world
      but for decades, transnational tobacco companies (TTCs) have had limited success
      infiltrating this market, due to their inability to compete in the kretek market.
      Kreteks are clove/tobacco cigarettes that most Indonesians smoke. OBJECTIVE: To
      determine how Phillip Morris International (PMI) and British American Tobacco
      (BAT) have now successfully achieved a substantial market presence in Indonesia.
      METHODS: We analyzed previously secret, tobacco industry documents, corporate
      reports on Indonesia operations, the Tobacco Trade press, Indonesia media, and
      "The Roadmap". RESULTS: Internal, corporate documents from BAT and PMI
      demonstrate that they had known for decades that kreteks are highly carcinogenic.
      Despite that knowledge, BAT and PMI now own and heavily market these products, as
      well as new more westernised versions of kreteks. BAT and PMI used their
      successful basic strategy of keeping cigarettes affordable by maintaining the
      social responsibility of smoking and opposing smoke-free workplace laws but in
      the 21st century, they added the acquisition of and westernisation of domestic
      kretek manufacturers as an additional strategy. These acquisitions allowed them
      to assert influences on health policy in Indonesia and to grow their business
      under current government policy embodied in the 2007-2020 Roadmap of Tobacco
      Products Industry and Excise Policy which calls for increased cigarette
      production by 12% over the next 15 years. CONCLUSION: PMI and Bat have
      successfully entered and are expanding their share in the Indonesia cigarette
      market. Despite the obvious and pervasive influence of the tobacco industry on
      policy decisions, the Indonesian government should ratify the FCTC and implement
      effective legislation to reduce tobacco consumption and exposure to tobacco smoke
      and revise the Roadmap to protect future generations of Indonesians.

PMID- 21852412
TI  - The effectiveness of integrated health information technologies across the phases
      of medication management: a systematic review of randomized controlled trials.
AB  - OBJECTIVE: The US Agency for Healthcare Research and Quality funded an evidence
      report to address seven questions on multiple aspects of the effectiveness of
      medication management information technology (MMIT) and its components
      (prescribing, order communication, dispensing, administering, and monitoring).
      MATERIALS AND METHODS: Medline and 11 other databases without language or date
      limitations to mid-2010. Randomized controlled trials (RCTs) assessing integrated
      MMIT were selected by two independent reviewers. Reviewers assessed study quality
      and extracted data. Senior staff checked accuracy. RESULTS: Most of the 87 RCTs
      focused on clinical decision support and computerized provider order entry
      systems, were performed in hospitals and clinics, included primarily physicians
      and sometimes nurses but not other health professionals, and studied process
      changes related to prescribing and monitoring medication. Processes of care
      improved for prescribing and monitoring mostly in hospital settings, but the few
      studies measuring clinical outcomes showed small or no improvements. Studies were
      performed most frequently in the USA (n=63), Europe (n=16), and Canada (n=6).
      DISCUSSION: Many studies had limited description of systems, installations,
      institutions, and targets of the intervention. Problems with methods and analyses
      were also found. Few studies addressed order communication, dispensing, or
      administering, non-physician prescribers or pharmacists and their MMIT tools, or
      patients and caregivers. Other study methods are also needed to completely
      understand the effects of MMIT. CONCLUSIONS: Almost half of MMIT interventions
      improved the process of care, but few studies measured clinical outcomes. This
      large body of literature, although instructive, is not uniformly distributed
      across settings, people, medication phases, or outcomes.

PMID- 21852414
TI  - The coronary artery disease-associated 9p21 variant and later life 20-year
      survival to cohort extinction.
AB  - BACKGROUND: Common variation at chromosome 9p21 (marked by rs10757278 or
      rs1333049) is associated with coronary artery disease (CAD) and peripheral
      vascular disease. A decreasing effect at older age was suggested, and effects on
      long-term mortality are unclear. We estimated 9p21 associations with CAD and all
      cause mortality in a CAD diagnosis-free older population. We also estimated
      classification gains on adding the variant to the Framingham Risk Score (FRS) for
      CAD. METHODS AND RESULTS: DNA was from an Established Populations for
      Epidemiological Study of the Elderly-Iowa cohort from 1988 (participants >71
      years), with death certificates obtained to 2008 for 92% of participants. Cox
      regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD
      diagnosis-free participants, 52% were heterozygous (CG) and 22% were homozygous
      (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in
      the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele
      was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08-1.30) and CAD
      (hazard ratio, 1.29; 95% CI, 1.08-1.56) mortality, independent of CAD risk
      factors. There was no association with stroke deaths. Variant associations with
      CAD mortality were attenuated after the age of 80 years (age-interaction term
      P=0.05). In age group 71 to 80 years, FRS classified as high risk 21% of
      respondents who died of CAD within 10 years; adding 9p21 identified 27% of
      respondents. CONCLUSIONS: In 71- to 80-year-old subjects free of CAD diagnoses,
      9p21 is associated with excess mortality, mainly attributed to CAD mortality.
      Adding 9p21 to the FRS may improve the targeting of CAD prevention in older
      people, but validation in independent samples is needed for confirmation.

PMID- 21852415
TI  - Arabidopsis Cys2/His2 zinc-finger proteins AZF1 and AZF2 negatively regulate
      abscisic acid-repressive and auxin-inducible genes under abiotic stress
      conditions.
AB  - In plants, abiotic stresses induce various physiological changes and growth
      inhibition that result in adaptive responses to these stresses. However, little
      is known about how such stresses cause plant growth inhibition. Many genes have
      been reported to be repressed in plants under abiotic stress conditions. ZPT2
      (for petunia [Petunia hybrida] zinc-finger protein 2)-related proteins with two
      Cys2/His2-type zinc-finger motifs and an ethylene-responsive element binding
      factor-associated amphiphilic repression motif are thought to function as
      transcriptional repressors. To characterize the roles of this type of
      transcriptional repressor under abiotic stress conditions, we analyzed the
      functions of two Arabidopsis (Arabidopsis thaliana) ZPT2-related genes that were
      induced by osmotic stress and abscisic acid: AZF1 (for Arabidopsis zinc-finger
      protein 1) and AZF2. The nuclear localization of these two proteins was observed
      in the roots under control conditions, and the accumulation of AZF2 was clearly
      detected in the nuclei of leaf cells under stress conditions. Transgenic plants
      overexpressing AZF1 and AZF2 were generated using stress-responsive promoters or
      the GVG chemical induction system. The overexpression of these genes caused
      severe damage to plant growth and viability. Transcriptome analyses of the
      transgenic plants demonstrated that AZF1 and AZF2 repressed various genes that
      were down-regulated by osmotic stress and abscisic acid treatment. Moreover, many
      auxin-responsive genes were found to be commonly down-regulated in the transgenic
      plants. Gel mobility shift assays revealed that both the AZF1 and AZF2 proteins
      bound to the promoter regions of these down-regulated genes. These results
      indicate that AZF1 and AZF2 function as transcriptional repressors involved in
      the inhibition of plant growth under abiotic stress conditions.

PMID- 21852417
TI  - Green light induces shade avoidance symptoms.
AB  - Light quality and quantity affect plant adaptation to changing light conditions.
      Certain wavelengths in the visible and near-visible spectrum are known to have
      discrete effects on plant growth and development, and the effects of red, far
      red, blue, and ultraviolet light have been well described. In this report, an
      effect of green light on Arabidopsis (Arabidopsis thaliana) rosette architecture
      is demonstrated using a narrow-bandwidth light-emitting diode-based lighting
      system. When green light was added to a background of constant red and blue
      light, plants exhibited elongation of petioles and upward leaf reorientation,
      symptoms consistent with those observed in a shaded light environment. The same
      green light-induced phenotypes were also observed in phytochrome (phy) and
      cryptochrome (cry) mutant backgrounds. To explore the molecular mechanism
      underlying the green light-induced response, the accumulation of shade-induced
      transcripts was measured in response to enriched green light environments.
      Transcripts that have been demonstrated to increase in abundance under far-red
      induced shade avoidance conditions either decrease or exhibit no change when
      green light is added. However, normal far-red light-associated transcript
      accumulation patterns are observed in cryptochrome mutants grown with
      supplemental green light, indicating that the green-absorbing form of
      cryptochrome is the photoreceptor active in limiting the green light induction of
      shade-associated transcripts. These results indicate that shade symptoms can be
      induced by the addition of green light and that cryptochrome receptors and an
      unknown light sensor participate in acclimation to the enriched green
      environment.

PMID- 21852418
TI  - Abiotic determinants to the spatial dynamics of dengue fever in Guangzhou.
AB  - Dengue fever (DF) is a mosquito-borne disease that significantly endangers the
      well-being of people in most tropical Asia-Pacific areas. The transmission of DF
      is inherently a spatial process, requiring susceptible humans encountering
      infectious mosquito. The relationships between humans, mosquito and environment
      underpin the dynamics and patterns of the epidemic. In this article, the
      objective is to find out the key abiotic factors in the spatial dynamics of DF.
      An interdisciplinary study has been carried out by taking advantage of
      statistics, geographical information science, and remote sensing technologies.
      The case study is the DF outbreak in the Chinese city of Guangzhou throughout the
      year of 2002--the most serious DF outbreak in the recent decade. This study shows
      that the presence and abundance of DF cases can be associated with (a)
      socioeconomic factors relating to urbanization and (b) meteorological factors
      favoring mosquito survival.

PMID- 21852416
TI  - The ZmASR1 protein influences branched-chain amino acid biosynthesis and
      maintains kernel yield in maize under water-limited conditions.
AB  - Abscisic acid-, stress-, and ripening-induced (ASR) proteins were first described
      about 15 years ago as accumulating to high levels during plant developmental
      processes and in response to diverse stresses. Currently, the effects of ASRs on
      water deficit tolerance and the ways in which their physiological and biochemical
      functions lead to this stress tolerance remain poorly understood. Here, we
      characterized the ASR gene family from maize (Zea mays), which contains nine
      paralogous genes, and showed that maize ASR1 (ZmASR1) was encoded by one of the
      most highly expressed paralogs. Ectopic expression of ZmASR1 had a large overall
      impact on maize yield that was maintained under water-limited stress conditions
      in the field. Comparative transcriptomic and proteomic analyses of wild-type and
      ZmASR1-overexpressing leaves led to the identification of three transcripts and
      16 proteins up- or down-regulated by ZmASR1. The majority of them were involved
      in primary and/or cellular metabolic processes, including branched-chain amino
      acid (BCAA) biosynthesis. Metabolomic and transcript analyses further indicated
      that ZmASR1-overexpressing plants showed a decrease in BCAA compounds and changes
      in BCAA-related gene expression in comparison with wild-type plants.
      Interestingly, within-group correlation matrix analysis revealed a close link
      between 13 decreased metabolites in ZmASR1-overexpressing leaves, including two
      BCAAs. Among these 13 metabolites, six were previously shown to be negatively
      correlated to biomass, suggesting that ZmASR1-dependent regulation of these 13
      metabolites might contribute to regulate leaf growth, resulting in improvement in
      kernel yield.

PMID- 21852419
TI  - Prevalence and correlates of perpetration of violence among young people: a
      population-based survey from Goa, India.
AB  - The aim of this study was to describe the prevalence and factors associated with
      perpetration of violence in young people in India. It was a cross-sectional
      survey of 3663 individuals (16-24 years old). Data on sociodemographics,
      sexual/physical violence, common mental disorders, and substance abuse were
      collected by face-to-face structured interviews. Logistic regression was used to
      estimate odds ratios for association of violence with various factors. Prevalence
      of physical violence in the past year was 10.2%. In both genders, younger age,
      urbanicity, being a victim of sexual abuse, common mental disorders, and tobacco
      use were associated with increased risk of physical violence. Being a victim of
      forced sexual intercourse and alcohol use was associated with violence in males;
      and not living with parents was associated with violence in females. Future
      research should be designed to tease out the pathways that underlie the
      associations, identified in the study, to derive potential preventive strategies.

PMID- 21852420
TI  - Evaluation of the determinants for acceptance of antenatal clinical breast
      examination in Taiwan.
AB  - Antenatal clinical breast examinations (ANCBEs) performed by physicians or nurses
      during prenatal care visits are recommended by the Department of Health in
      Taiwan. This study aimed to assess the level of acceptance of ANCBE in Taiwan and
      the determinants associated with behavior toward them. This was a clinic-based
      study conducted from 30 November 2008 to 30 April 2009 by using a structured
      questionnaire for 492 pregnant women. Only 2.8% of the patients received ANCBE,
      and 95.9% were not aware of the availability of ANCBE. History of breast surgery
      and awareness of ANCBE availability were significantly associated with receiving
      ANCBE (P < .001). Furthermore, multiparity was statistically different for the
      awareness of ANCBE availability (P = .04). Acceptance of ANCBE was determined by
      personal history of breast surgery and awareness of ANCBE availability.

PMID- 21852421
TI  - Factors associated with preferences for health system goals in Japan: a pilot
      study of the World Health Survey.
AB  - Preferences among people for health system goals are important determinants in
      developing health policy. The aim of this study was to determine preferences for
      health system goals and their associations with sociodemographic characteristics
      in Japan. Participants were randomly selected from the general population in 5
      prefectures and were asked to rank 5 health system goals in order of preference:
      health, health inequality, responsiveness, responsiveness inequality, and fair
      financing. Associations between sociodemographic characteristics and preferences
      for health system goals were examined using multinomial logistic regression
      analysis. A total of 4936 persons responded to this study. Health system goals in
      order of preference were health inequality (37.6%), responsiveness inequality
      (20.9%), health (18.4%), responsiveness (16.0%), and fair financing (7.1%).
      Sociodemographic characteristics such as gender, age, family status, education
      completed, and usage of health care services were associated with the preferred
      health system goal. Health policy makers should take these associations into
      account when developing prospective policy.

PMID- 21852422
TI  - Regional disparities in prenatal care services in rural China.
AB  - The study compared the prenatal care programs in the Central-East, Northwest, and
      Southwest regions of China. Data were collected on 14 indicators of the quality
      of the prenatal care process, as well as the percentage of women with high-risk
      pregnancies who were screened. The average number of prenatal examinations for
      those women who received prenatal care was 5.01, and 62.6% of pregnant women had
      their first examination within 12 weeks of their pregnancy. About 35% of these
      pregnant women had at least 1 high-risk screening, and 20.8% had 3 high-risk
      screenings. Among the 3 regions, the Central-East region had the best overall
      quality prenatal services, and the Northwest area had the poorest quality. The
      quality of prenatal health care in poor, rural China is in need of improvement.

PMID- 21852423
TI  - Turning postgraduate students' research into publications: a survey of New
      Zealand masters in public health students.
AB  - The authors attempted to contact all 157 graduates from the University of
      Auckland's Master's in Public Health (MPH) program who completed theses from 1991
      to 2005 about publications arising from their research. Of the 104 students
      contacted, 77 (74%) completed the questionnaire: 34 (45%) submitted a total of 46
      articles, 31 (66%) of which were accepted or published. An expectation of
      publication and being supported financially were both associated with submission
      for publication. The most commonly reported barriers were lack of time (62%),
      lack of staff support (35%), and low confidence in ability to write (29%). For
      those regarding time as a barrier, work demands were commonly cited (90%).
      Sustained commitment from supervisors plus practical support (seminars,
      workshops, and cosupervision) was considered likely to be helpful. More effective
      supervisor-student engagement, funding, and setting an expectation of publication
      could increase MPH research outputs, but the additional supervisor workload must
      be realistic.

PMID- 21852424
TI  - The myosin-interacting protein SMYD1 is essential for sarcomere organization.
AB  - Assembly, maintenance and renewal of sarcomeres require highly organized and
      balanced folding, transport, modification and degradation of sarcomeric proteins.
      However, the molecules that mediate these processes are largely unknown. Here, we
      isolated the zebrafish mutant flatline (fla), which shows disturbed sarcomere
      assembly exclusively in heart and fast-twitch skeletal muscle. By positional
      cloning we identified a nonsense mutation within the SET- and MYND-domain
      containing protein 1 gene (smyd1) to be responsible for the fla phenotype. We
      found SMYD1 expression to be restricted to the heart and fast-twitch skeletal
      muscle cells. Within these cell types, SMYD1 localizes to both the sarcomeric M
      line, where it physically associates with myosin, and the nucleus, where it
      supposedly represses transcription through its SET and MYND domains. However,
      although we found transcript levels of thick filament chaperones, such as Hsp90a1
      and UNC-45b, to be severely upregulated in fla, its histone methyltransferase
      activity - mainly responsible for the nuclear function of SMYD1 - is dispensable
      for sarcomerogenesis. Accordingly, sarcomere assembly in fla mutant embryos can
      be reconstituted by ectopically expressing histone methyltransferase-deficient
      SMYD1. By contrast, ectopic expression of myosin-binding-deficient SMYD1 does not
      rescue fla mutants, implicating an essential role for the SMYD1-myosin
      interaction in cardiac and fast-twitch skeletal muscle thick filament assembly.

PMID- 21852425
TI  - SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and
      sustained spermatogenesis.
AB  - SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically
      associate with somatic chromatin, to modulate chromatin compaction and to be
      important for proper cell division. Here, we report on the expression of SPOC1 in
      promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated
      spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the
      biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a
      gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1(-/-) animals
      displayed a pronounced progressive loss of germ cells from an initially normal
      germ epithelium of the testis tubules leading to testis hypoplasia. This loss
      first affected non-SSC stages of germ cells and then, at a later time point, the
      undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at
      >20 weeks of age) was preceded by a transient increase in the number of
      undifferentiated A(aligned) (A(al)) spermatogonia in younger mice (at >10 weeks
      of age). The number of primary Spoc1(-/-) gonocytes, the proliferation of germ
      cells, and the initiation and progression of meiosis was normal, but we noted a
      significantly elevated level of apoptosis in the Spoc1(-/-) testis. Taken
      together, the data argue that SPOC1 is indispensable for stem cell
      differentiation in the testis and for sustained spermatogenesis.

PMID- 21852426
TI  - CFTR anion channel modulates expression of human transmembrane mucin MUC3 through
      the PDZ protein GOPC.
AB  - The transmembrane mucins in the enterocyte are type 1 transmembrane proteins with
      long and rigid mucin domains, rich in proline, threonine and serine residues that
      carry numerous O-glycans. Three of these mucins, MUC3, MUC12 and MUC17 are unique
      in harboring C-terminal class I PDZ motifs, making them suitable ligands for PDZ
      proteins. A screening of 123 different human PDZ domains for binding to MUC3
      identified a strong interaction with the PDZ protein GOPC (Golgi-associated PDZ
      and coiled-coil motif-containing protein). This interaction was mediated by the C
      terminal PDZ motif of MUC3, binding to the single GOPC PDZ domain. GOPC is also a
      binding partner for cystic fibrosis transmembrane conductance regulator (CFTR)
      that directs CFTR for degradation. Overexpression of GOPC downregulated the total
      levels of MUC3, an effect that was reversed by introducing CFTR. The results
      suggest that CFTR and MUC3 compete for binding to GOPC, which in turn can
      regulate levels of these two proteins. For the first time a direct coupling
      between mucins and the CFTR channel is demonstrated, a finding that will shed
      further light on the still poorly understood relationship between cystic fibrosis
      and the mucus phenotype of this disease.

PMID- 21852427
TI  - Activation of metabotropic GABA receptors increases the energy barrier for
      vesicle fusion.
AB  - Neurotransmitter release from presynaptic terminals is under the tight control of
      various metabotropic receptors. We report here that in addition to the regulation
      of Ca(2+) channel activity, metabotropic GABA(B) receptors (GABA(B)Rs) at murine
      hippocampal glutamatergic synapses utilize an inhibitory pathway that directly
      targets the synaptic vesicle release machinery. Acute application of the GABA(B)R
      agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs
      independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose
      solutions, we find that the size of the readily releasable pool remains unchanged
      by GABA(B)R activation, but the sensitivity of primed vesicles to hypertonic
      stimuli appears lowered as the response amplitudes at intermediate sucrose
      concentrations are smaller and release kinetics are slowed. These data show that
      presynaptic GABA(B)Rs can inhibit neurotransmitter release directly by increasing
      the energy barrier for vesicle fusion.

PMID- 21852428
TI  - New impact factor number reflects sustained and enhanced growth.

PMID- 21852429
TI  - Proteomics of gliomas: initial biomarker discovery and evolution of technology.
AB  - Gliomas are a group of aggressive brain tumors that diffusely infiltrate adjacent
      brain tissues, rendering them largely incurable, even with multiple treatment
      modalities and agents. Mostly asymptomatic at early stages, they present in
      several subtypes with astrocytic or oligodendrocytic features and invariably
      progress to malignant forms. Gliomas are difficult to classify precisely because
      of interobserver variability during histopathologic grading. Identifying
      biological signatures of each glioma subtype through protein biomarker profiling
      of tumor or tumor-proximal fluids is therefore of high priority. Such profiling
      not only may provide clues regarding tumor classification but may identify
      clinical biomarkers and pathologic targets for the development of personalized
      treatments. In the past decade, differential proteomic profiling techniques have
      utilized tumor, cerebrospinal fluid, and plasma from glioma patients to identify
      the first candidate diagnostic, prognostic, predictive, and therapeutic response
      markers, highlighting the potential for glioma biomarker discovery. The number of
      markers identified, however, has been limited, their reproducibility between
      studies is unclear, and none have been validated for clinical use. Recent
      technological advancements in methodologies for high-throughput profiling, which
      provide easy access, rapid screening, low sample consumption, and accurate
      protein identification, are anticipated to accelerate brain tumor biomarker
      discovery. Reliable tools for biomarker verification forecast translation of the
      biomarkers into clinical diagnostics in the foreseeable future. Herein we update
      the reader on the recent trends and directions in glioma proteomics, including
      key findings and established and emerging technologies for analysis, together
      with challenges we are still facing in identifying and verifying potential glioma
      biomarkers.

PMID- 21852430
TI  - Reelin supplementation enhances cognitive ability, synaptic plasticity, and
      dendritic spine density.
AB  - Apolipoprotein receptors belong to an evolutionarily conserved surface receptor
      family that has intimate roles in the modulation of synaptic plasticity and is
      necessary for proper hippocampal-dependent memory formation. The known
      lipoprotein receptor ligand Reelin is important for normal synaptic plasticity,
      dendritic morphology, and cognitive function; however, the in vivo effect of
      enhanced Reelin signaling on cognitive function and synaptic plasticity in wild
      type mice is unknown. The present studies test the hypothesis that in vivo
      enhancement of Reelin signaling can alter synaptic plasticity and ultimately
      influence processes of learning and memory. Purified recombinant Reelin was
      injected bilaterally into the ventricles of wild-type mice. We demonstrate that a
      single in vivo injection of Reelin increased activation of adaptor protein
      Disabled-1 and cAMP-response element binding protein after 15 min. These changes
      correlated with increased dendritic spine density, increased hippocampal CA1 long
      term potentiation (LTP), and enhanced performance in associative and spatial
      learning and memory. The present study suggests that an acute elevation of in
      vivo Reelin can have long-term effects on synaptic function and cognitive ability
      in wild-type mice.

PMID- 21852431
TI  - Effects of modality on the neural correlates of encoding processes supporting
      recollection and familiarity.
AB  - Prior research has demonstrated that the neural correlates of successful encoding
      ("subsequent memory effects") partially overlap with neural regions selectively
      engaged by the on-line demands of the study task. The primary goal of the present
      experiment was to determine whether this overlap is associated solely with
      encoding processes supporting later recollection, or whether overlapping
      subsequent memory and study condition effects are also evident when later memory
      is familiarity-based. Subjects (N = 17) underwent fMRI scanning while studying a
      series of visually and auditorily presented words. Memory for the words was
      subsequently tested with a modified Remember/Know procedure. Auditorily selective
      subsequent familiarity effects were evident in bilateral temporal regions that
      also responded preferentially to auditory items. Although other interpretations
      are possible, these findings suggest that overlap between study condition
      selective subsequent memory effects and regions selectively sensitive to study
      demands is not uniquely associated with later recollection. In addition, modality
      independent subsequent memory effects were identified in several cortical
      regions. In every case, the effects were greatest for later recollected items,
      and smaller for items later recognized on the basis of familiarity. The
      implications of this quantitative dissociation for dual-process models of
      recognition memory are discussed.

PMID- 21852433
TI  - The radiation exposure controversy.

PMID- 21852432
TI  - RSK2 signaling in brain habenula contributes to place aversion learning.
AB  - RSK2 is a Ser/Thr kinase acting in the Ras/MAPK pathway. Rsk2 gene deficiency
      leads to the Coffin-Lowry Syndrome, notably characterized by cognitive deficits.
      We found that mrsk2 knockout mice are unable to associate an aversive stimulus
      with context in a lithium-induced conditioned place aversion task requiring both
      high-order cognition and emotional processing. Virally mediated shRNA-RSK2
      knockdown in the habenula, whose involvement in cognition is receiving increasing
      attention, also ablated contextual conditioning. RSK2 signaling in the habenula,
      therefore, is essential for this task. Our study reveals a novel role for RSK2 in
      cognitive processes and uncovers the critical implication of an intriguing brain
      structure in place aversion learning.

PMID- 21852434
TI  - New editor and member of the editorial board.

PMID- 21852435
TI  - Acta Radiologica Short Reports to be launched in September.

PMID- 21852436
TI  - Assessment of the right ventricular function in patients with chronic obstructive
      pulmonary disease using MRI.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often associated with
      changes of the structure and the function of the right ventricle (RV). Therefore,
      the assessment of right ventricular function and myocardial mass (MM) is
      clinically important for the evaluation of the severity of COPD, which may
      provide an objective basis for therapeutic strategy. PURPOSE: To assess the right
      ventricular function and RV MM in patients with mild to severe COPD using
      magnetic resonance imaging (MRI). MATERIAL AND METHODS: We prospectively studied
      49 COPD patients determined by the pulmonary function test (PFT). Using the
      Global Initiative for COPD classification, the COPD patients were divided into
      three groups according to the severity of the disease: group I = mild (n = 18);
      group II = moderate (n = 16); and group III = severe (n = 15). The patient groups
      were compared to a control group consisting of 30 age-matched, healthy, non
      smoking subjects. The RV function and RV MM were obtained by 1.5T cardiac MRI in
      all of the four groups. The results were compared among the four groups using the
      ANOVA. Pearson's correlation was used to evaluate the relationship between the
      right ventricular ejection fraction (RVEF) and MM with the PFT results in COPD
      patients. RESULTS: The RVEF was significantly lower in group III than in the
      other groups (P < 0.01). The RV MM differed significantly among all groups (P <
      0.01) and gradually increased with the severity of COPD (P < 0.01). The
      correlation was significant between the MRI results and forced expiratory volume
      in 1 s (r = 0.860 for RVEF, r = -0.838 for RV MM) in COPD patients. CONCLUSION:
      The RVEF and RV MM measured by MRI correlate significantly with the severity of
      disease as determined by PFT in patients with COPD.

PMID- 21852437
TI  - The efficacy of 2D, non-linear noise reduction filtering in cardiac imaging: a
      pilot study.
AB  - BACKGROUND: Computed tomography (CT) is becoming increasingly popular as a non
      invasive method for visualizing the coronary arteries but patient radiation doses
      are still an issue. Postprocessing filters such as 2D adaptive non-linear filters
      might help to reduce the dose without loss of image quality. PURPOSE: To
      investigate whether the use of a 2D, non-linear adaptive noise reduction filter
      can improve image quality in cardiac computed tomography angiography (CCTA).
      MATERIAL AND METHODS: CCTA examinations were performed in 36 clinical patients on
      a dual source CT using two patient dose levels: maximum dose during diastole and
      reduced dose (20% of maximum dose) during systole. One full-dose and one reduced
      dose image were selected from each of the examinations. The reduced-dose image
      was duplicated and one copy postprocessed using a 2D non-linear adaptive noise
      reduction filter, resulting in three images per patient. Image quality was
      assessed using visual grading with three criteria from the European guidelines
      for assessment of image quality and two additional criteria regarding the left
      main artery and the overall image quality. Also, the HU value and its standard
      deviation were measured in the ascending and descending aorta. Data were analyzed
      using Visual Grading Regression and paired t-test. RESULT: For all five criteria,
      there was a significant (P < 0.01 or better) improvement in perceived image
      quality when comparing postprocessed low-dose images with low-dose images without
      noise reduction. Comparing full dose images with postprocessed low-dose images
      resulted in a considerably larger, significant (P < 0.001) difference. Also,
      there was a significant reduction of the standard deviation of the HU values in
      the ascending and descending aorta when comparing postprocessed low-dose images
      with low-dose images without postprocessing. CONCLUSION: Even with an 80% dose
      reduction, there was a significant improvement in the perceived image quality
      when using a 2D noise-reduction filter, though not approaching the quality of
      full-dose images. This indicates that cardiac CT examinations could benefit from
      noise-reducing postprocessing with 2D non-linear adaptive filters.

PMID- 21852438
TI  - Using DWIBS MRI technique as an alternative to bone scan or PET scan for whole
      body imaging in oncology patients.

PMID- 21852439
TI  - Combination of high resolution and color Doppler ultrasound in diagnosis of
      carpal tunnel syndrome.

PMID- 21852440
TI  - 3 Rs: rituximab, remission, relapse.

PMID- 21852441
TI  - Platelets get the message.

PMID- 21852442
TI  - Inflammation & the platelet histone trap.

PMID- 21852443
TI  - Supply-side economics finds the thymus.

PMID- 21852444
TI  - X-ALD: centralize care in an international network.

PMID- 21852445
TI  - Channeling the homocysteine chapel.

PMID- 21852446
TI  - Beating the rap in angiogenesis.

PMID- 21852448
TI  - A statistical model of facial attractiveness.
AB  - Previous research has identified facial averageness and sexual dimorphism as
      important factors in facial attractiveness. The averageness and sexual dimorphism
      accounts provide important first steps in understanding what makes faces
      attractive, and should be valued for their parsimony. However, we show that they
      explain relatively little of the variance in facial attractiveness, particularly
      for male faces. As an alternative to these accounts, we built a regression model
      that defines attractiveness as a function of a face's position in a
      multidimensional face space. The model provides much more predictive power than
      the averageness and sexual dimorphism accounts and reveals previously unreported
      components of attractiveness. The model shows that averageness is attractive in
      some dimensions but not in others and resolves previous contradictory reports
      about the effects of sexual dimorphism on the attractiveness of male faces.

PMID- 21852449
TI  - Known risk factors for violence predict 12-month-old infants' aggressiveness with
      peers.
AB  - This study tested the hypothesis that 12-month-old infants' use of force against
      peers is associated with known risk factors for violence. We conducted a
      prospective longitudinal study, which included laboratory observations of
      firstborn British infants (N = 271) during simulated birthday parties. No gender
      differences in aggressiveness were observed. The infants' observed aggressiveness
      was significantly correlated with mothers' mood disorder during pregnancy and
      with mothers' history of conduct problems. Infants' observed aggressiveness was
      correlated with parents' ratings of infants' anger and aggression, which were
      also predicted by mothers' mood disorder and history of conduct problems. Our
      findings indicate that infants at risk for serious aggression can already be
      identified when the motor ability to use physical force first enters the human
      repertoire.

PMID- 21852450
TI  - Mutual interference between statistical summary perception and statistical
      learning.
AB  - The visual system is an efficient statistician, extracting statistical summaries
      over sets of objects (statistical summary perception) and statistical
      regularities among individual objects (statistical learning). Although these two
      kinds of statistical processing have been studied extensively in isolation, their
      relationship is not yet understood. We first examined how statistical summary
      perception influences statistical learning by manipulating the task that
      participants performed over sets of objects containing statistical regularities
      (Experiment 1). Participants who performed a summary task showed no statistical
      learning of the regularities, whereas those who performed control tasks showed
      robust learning. We then examined how statistical learning influences statistical
      summary perception by manipulating whether the sets being summarized contained
      regularities (Experiment 2) and whether such regularities had already been
      learned (Experiment 3). The accuracy of summary judgments improved when
      regularities were removed and when learning had occurred in advance. In sum,
      calculating summary statistics impeded statistical learning, and extracting
      statistical regularities impeded statistical summary perception. This mutual
      interference suggests that statistical summary perception and statistical
      learning are fundamentally related.

PMID- 21852451
TI  - Pop-out without awareness: unseen feature singletons capture attention only when
      top-down attention is available.
AB  - Visual pop-out occurs when a unique visual target (e.g., a feature singleton) is
      present in a set of homogeneous distractors. However, the role of visual
      awareness in this process remains unclear. In the experiments reported here, we
      showed that even though subjects were not aware of a suppressed pop-out display,
      their subsequent performance on an orientation-discrimination task was
      significantly better at the pop-out location than at a control location. These
      results indicate that conscious visual awareness of a feature singleton is not
      necessary for it to attract attention. Furthermore, the subliminal pop-out effect
      disappeared when subjects diverted their attention toward a rapid sequential
      visual presentation task while presented with the same subliminal pop-out
      display. These results suggest that top-down attention is necessary for the
      subliminal pop-out effect and that the cognitive processes underlying attention
      and awareness are somewhat independent.

PMID- 21852452
TI  - JC virus antibody and viremia as predictors of progressive multifocal
      leukoencephalopathy in human immunodeficiency virus-1-infected individuals.
AB  - We examined whether prediagnostic John Cunningham virus (JCV) antibodies and
      viremia are predictors of progressive multifocal leukoencephalopathy (PML) in 83
      PML cases and 240 human immunodeficiency virus (HIV) disease-matched controls.
      JCV viremia was not predictive of PML, but some patients showed higher anti-JCV
      immunoglobulin G (IgG) responses 6 months prior to diagnosis.

PMID- 21852453
TI  - Soil nitrite as a source of atmospheric HONO and OH radicals.
AB  - Hydroxyl radicals (OH) are a key species in atmospheric photochemistry. In the
      lower atmosphere, up to ~30% of the primary OH radical production is attributed
      to the photolysis of nitrous acid (HONO), and field observations suggest a large
      missing source of HONO. We show that soil nitrite can release HONO and explain
      the reported strength and diurnal variation of the missing source. Fertilized
      soils with low pH appear to be particularly strong sources of HONO and OH. Thus,
      agricultural activities and land-use changes may strongly influence the oxidizing
      capacity of the atmosphere. Because of the widespread occurrence of nitrite
      producing microbes, the release of HONO from soil may also be important in
      natural environments, including forests and boreal regions.

PMID- 21852454
TI  - Human sperm binding is mediated by the sialyl-Lewis(x) oligosaccharide on the
      zona pellucida.
AB  - Human fertilization begins when spermatozoa bind to the extracellular matrix
      coating of the oocyte, known as the zona pellucida (ZP). One spermatozoan then
      penetrates this matrix and fuses with the egg cell, generating a zygote. Although
      carbohydrate sequences on the ZP have been implicated in sperm binding, the
      nature of the ligand was unknown. Here, ultrasensitive mass spectrometric
      analyses revealed that the sialyl-Lewis(x) sequence [NeuAcalpha2-3Galbeta1
      4(Fucalpha1-3)GlcNAc], a well-known selectin ligand, is the most abundant
      terminal sequence on the N- and O-glycans of human ZP. Sperm-ZP binding was
      largely inhibited by glycoconjugates terminated with sialyl-Lewis(x) sequences or
      by antibodies directed against this sequence. Thus, the sialyl-Lewis(x) sequence
      represents the major carbohydrate ligand for human sperm-egg binding.

PMID- 21852455
TI  - Unfolded proteins are Ire1-activating ligands that directly induce the unfolded
      protein response.
AB  - The unfolded protein response (UPR) detects the accumulation of unfolded proteins
      in the endoplasmic reticulum (ER) and adjusts the protein-folding capacity to the
      needs of the cell. Under conditions of ER stress, the transmembrane protein Ire1
      oligomerizes to activate its cytoplasmic kinase and ribonuclease domains. It is
      unclear what feature of ER stress Ire1 detects. We found that the core ER-lumenal
      domain (cLD) of yeast Ire1 binds to unfolded proteins in yeast cells and to
      peptides primarily composed of basic and hydrophobic residues in vitro. Mutation
      of amino acid side chains exposed in a putative peptide-binding groove of Ire1
      cLD impaired peptide binding. Peptide binding caused Ire1 cLD oligomerization in
      vitro, suggesting that direct binding to unfolded proteins activates the UPR.

PMID- 21852456
TI  - Recently formed polyploid plants diversify at lower rates.
AB  - Polyploidy, the doubling of genomic content, is a widespread feature, especially
      among plants, yet its macroevolutionary impacts are contentious. Traditionally,
      polyploidy has been considered an evolutionary dead end, whereas recent genomic
      studies suggest that polyploidy has been a key driver of macroevolutionary
      success. We examined the consequences of polyploidy on the time scale of genera
      across a diverse set of vascular plants, encompassing hundreds of inferred
      polyploidization events. Likelihood-based analyses indicate that polyploids
      generally exhibit lower speciation rates and higher extinction rates than
      diploids, providing the first quantitative corroboration of the dead-end
      hypothesis. The increased speciation rates of diploids can, in part, be ascribed
      to their capacity to speciate via polyploidy. Only particularly fit lineages of
      polyploids may persist to enjoy longer-term evolutionary success.

PMID- 21852458
TI  - Getting education right.

PMID- 21852457
TI  - Ice flow of the Antarctic ice sheet.
AB  - We present a reference, comprehensive, high-resolution, digital mosaic of ice
      motion in Antarctica assembled from multiple satellite interferometric synthetic
      aperture radar data acquired during the International Polar Year 2007 to 2009.
      The data reveal widespread, patterned, enhanced flow with tributary glaciers
      reaching hundreds to thousands of kilometers inland over the entire continent.
      This view of ice sheet motion emphasizes the importance of basal-slip-dominated
      tributary flow over deformation-dominated ice sheet flow, redefines our
      understanding of ice sheet dynamics, and has far-reaching implications for the
      reconstruction and prediction of ice sheet evolution.

PMID- 21852462
TI  - Biomedical research funding. NIH uncovers racial disparity in grant awards.

PMID- 21852463
TI  - Biomedical research funding. A minority viewpoint.

PMID- 21852464
TI  - Antarctic science. U.S. icebreaking woes threaten McMurdo resupply, research
      plans.

PMID- 21852465
TI  - Newsmaker interview: David Morrison. Into the stretch for science's point man on
      doomsday.

PMID- 21852466
TI  - Scientific community. Mass exodus roils Brazilian neuroscience institute.

PMID- 21852467
TI  - Exoplanetary research. A distant glimpse of alien life?

PMID- 21852468
TI  - Infectious diseases. Drug developers finally take aim at a neglected disease.

PMID- 21852469
TI  - Infectious diseases. A tropical disease hits the road.

PMID- 21852470
TI  - Ecosystem rates of transformation matter.

PMID- 21852471
TI  - Invasives: classify with care.

PMID- 21852472
TI  - Invasives: sea of data still to come.

PMID- 21852474
TI  - Museums and archives in peril.

PMID- 21852476
TI  - Sociology. Weaving a richer tapestry in biomedical science.

PMID- 21852477
TI  - Cancer. Aneuploidy drives a mutator phenotype in cancer.

PMID- 21852478
TI  - Microbiology. Quantifying malaria dynamics within the host.

PMID- 21852480
TI  - Evolution. CNCing is believing.

PMID- 21852479
TI  - Immunology. The adjuvant effects of antibodies.

PMID- 21852481
TI  - Chemistry. Taking the pulse of molecular rotational spectroscopy.

PMID- 21852482
TI  - Investing early in education. Laying the foundation for lifetime learning.
      Introduction.

PMID- 21852483
TI  - Past successes shape effort to expand early intervention.

PMID- 21852484
TI  - Giving children a head start is possible--but it's not easy.

PMID- 21852485
TI  - A passion for early education. Interview by Jeffrey Mervis.

PMID- 21852486
TI  - Interventions shown to aid executive function development in children 4 to 12
      years old.
AB  - To be successful takes creativity, flexibility, self-control, and discipline.
      Central to all those are executive functions, including mentally playing with
      ideas, giving a considered rather than an impulsive response, and staying
      focused. Diverse activities have been shown to improve children's executive
      functions: computerized training, noncomputerized games, aerobics, martial arts,
      yoga, mindfulness, and school curricula. All successful programs involve repeated
      practice and progressively increase the challenge to executive functions.
      Children with worse executive functions benefit most from these activities; thus,
      early executive-function training may avert widening achievement gaps later. To
      improve executive functions, focusing narrowly on them may not be as effective as
      also addressing emotional and social development (as do curricula that improve
      executive functions) and physical development (shown by positive effects of
      aerobics, martial arts, and yoga).

PMID- 21852487
TI  - Teachers' language practices and academic outcomes of preschool children.
AB  - Early childhood programs have long been known to be beneficial to children from
      low-income backgrounds, but recent studies have cast doubt on their ability to
      substantially increase the rate of children's academic achievement. This Review
      examines research on the role of language in later reading, describes home and
      classroom factors that foster early language growth, and reviews research on
      preschool interventions. It argues that one reason interventions are not having
      as great an impact as desired is because they fail to substantially change the
      capacity of teachers to support children's language and associated conceptual
      knowledge.

PMID- 21852488
TI  - Early childhood mathematics intervention.
AB  - Preschool and primary grade children have the capacity to learn substantial
      mathematics, but many children lack opportunities to do so. Too many children not
      only start behind their more advantaged peers, but also begin a negative
      trajectory in mathematics. Interventions designed to facilitate their
      mathematical learning during ages 3 to 5 years have a strong positive effect on
      these children's lives for many years thereafter.

PMID- 21852489
TI  - Educational interventions to advance children's scientific thinking.
AB  - The goal of science education interventions is to nurture, enrich, and sustain
      children's natural and spontaneous interest in scientific knowledge and
      procedures. We present taxonomy for classifying different types of research on
      scientific thinking from the perspective of cognitive development and associated
      attempts to teach science. We summarize the literature on the early--unschooled-
      development of scientific thinking, and then focus on recent research on how best
      to teach science to children from preschool to middle school. We summarize some
      of the current disagreements in the field of science education and offer some
      suggestions on ways to continue to advance the science of science instruction.

PMID- 21852491
TI  - From science to policy in early childhood education.
AB  - This paper examines the relationship between scientific research and public
      policy. After explaining why the simple conversion of research into public law is
      unlikely, several factors are identified that can promote the use of research by
      public officials. Examples of use and non-use are cited from early childhood
      education, where empirical evidence on program effects is relatively strong. Some
      specific suggestions are offered for improving the connection between science and
      public policy.

PMID- 21852490
TI  - Effectiveness of early educational intervention.
AB  - Early educational intervention has been proposed to partially offset the impacts
      of poverty and inadequate learning environments on child development and school
      success. A broad range of early educational interventions are found to produce
      meaningful, lasting effects on cognitive, social, and schooling outcomes.
      However, all interventions are not equally effective. Two major U.S. programs
      perform relatively poorly. Research provides some guidance regarding the features
      of highly effective programs, but much remains to be learned. New experimental
      studies of key program features would have a high payoff.

PMID- 21852492
TI  - Protecting brains, not simply stimulating minds.
AB  - Curricular enhancements in early childhood education that are guided by the
      science of learning must be augmented by protective interventions informed by the
      biology of adversity. The same neuroplasticity that leaves emotional regulation,
      behavioral adaptation, and executive functioning skills vulnerable to early
      disruption by stressful environments also enables their successful development
      through focused interventions during sensitive periods in their maturation. The
      early childhood field should therefore combine cognitive-linguistic enrichment
      with greater attention to preventing, reducing, or mitigating the consequences of
      significant adversity on the developing brain. Guided by this enhanced theory of
      change, scientists, practitioners, and policy-makers must work together to
      design, implement, and evaluate innovative strategies to produce substantially
      greater impacts than those achieved by existing programs.

PMID- 21852494
TI  - Detection of emerging sunspot regions in the solar interior.
AB  - Sunspots are regions where strong magnetic fields emerge from the solar interior
      and where major eruptive events occur. These energetic events can cause power
      outages, interrupt telecommunication and navigation services, and pose hazards to
      astronauts. We detected subsurface signatures of emerging sunspot regions before
      they appeared on the solar disc. Strong acoustic travel-time anomalies of an
      order of 12 to 16 seconds were detected as deep as 65,000 kilometers. These
      anomalies were associated with magnetic structures that emerged with an average
      speed of 0.3 to 0.6 kilometer per second and caused high peaks in the
      photospheric magnetic flux rate 1 to 2 days after the detection of the anomalies.
      Thus, synoptic imaging of subsurface magnetic activity may allow anticipation of
      large sunspot regions before they become visible, improving space weather
      forecast.

PMID- 21852493
TI  - Partitioning regulatory mechanisms of within-host malaria dynamics using the
      effective propagation number.
AB  - Immune clearance and resource limitation (via red blood cell depletion) shape the
      peaks and troughs of malaria parasitemia, which in turn affect disease severity
      and transmission. Quantitatively partitioning the relative roles of these effects
      through time is challenging. Using data from rodent malaria, we estimated the
      effective propagation number, which reflects the relative importance of
      contrasting within-host control mechanisms through time and is sensitive to the
      inoculating parasite dose. Our analysis showed that the capacity of innate
      responses to restrict initial parasite growth saturates with parasite dose and
      that experimentally enhanced innate immunity can affect parasite density
      indirectly via resource depletion. Such a statistical approach offers a tool to
      improve targeting of drugs or vaccines for human therapy by revealing the
      dynamics and interactions of within-host regulatory mechanisms.

PMID- 21852495
TI  - Visualizing individual nitrogen dopants in monolayer graphene.
AB  - In monolayer graphene, substitutional doping during growth can be used to alter
      its electronic properties. We used scanning tunneling microscopy, Raman
      spectroscopy, x-ray spectroscopy, and first principles calculations to
      characterize individual nitrogen dopants in monolayer graphene grown on a copper
      substrate. Individual nitrogen atoms were incorporated as graphitic dopants, and
      a fraction of the extra electron on each nitrogen atom was delocalized into the
      graphene lattice. The electronic structure of nitrogen-doped graphene was
      strongly modified only within a few lattice spacings of the site of the nitrogen
      dopant. These findings show that chemical doping is a promising route to
      achieving high-quality graphene films with a large carrier concentration.

PMID- 21852496
TI  - Guided growth of millimeter-long horizontal nanowires with controlled
      orientations.
AB  - The large-scale assembly of nanowires with controlled orientation on surfaces
      remains one challenge preventing their integration into practical devices. We
      report the vapor-liquid-solid growth of aligned, millimeter-long, horizontal GaN
      nanowires with controlled crystallographic orientations on different planes of
      sapphire. The growth directions, crystallographic orientation, and faceting of
      the nanowires vary with each surface orientation, as determined by their
      epitaxial relationship with the substrate, as well as by a graphoepitaxial effect
      that guides their growth along surface steps and grooves. Despite their
      interaction with the surface, these horizontally grown nanowires display few
      structural defects, exhibiting optical and electronic properties comparable to
      those of vertically grown nanowires. This paves the way to highly controlled
      nanowire structures with potential applications not available by other means.

PMID- 21852497
TI  - A main group metal sandwich: five lithium cations jammed between two corannulene
      tetraanion decks.
AB  - Lithium-coordinated polyaromatic anions such as tetrareduced corannulene,
      C(20)H(10)(4-) (1(4-)), are useful substrates to model and ultimately improve the
      graphitic electrodes in lithium-ion (Li(+)) batteries. Previous studies suggested
      that 1(4-) forms dimers encasing four Li(+) ions in solution. Here, we report a
      single-crystal x-ray diffraction analysis confirming the formation of a sandwich
      type supramolecular aggregate with a high degree of alkali metal intercalation.
      In contrast to the prior model, our data reveal that five Li(+) ions are
      sandwiched between the two tetrareduced corannulene decks, and (7)Li nuclear
      magnetic resonance spectroscopy delineates a conserved structure in
      tetrahydrofuran solution. Remarkably, the sandwich is robust in both solution and
      solid states even in the presence of crown ethers that compete for Li(+)
      coordination. These results should help elucidate Li(+) intercalation motifs
      between curved carbon surfaces more broadly.

PMID- 21852498
TI  - Race, ethnicity, and NIH research awards.
AB  - We investigated the association between a U.S. National Institutes of Health
      (NIH) R01 applicant's self-identified race or ethnicity and the probability of
      receiving an award by using data from the NIH IMPAC II grant database, the
      Thomson Reuters Web of Science, and other sources. Although proposals with strong
      priority scores were equally likely to be funded regardless of race, we find that
      Asians are 4 percentage points and black or African-American applicants are 13
      percentage points less likely to receive NIH investigator-initiated research
      funding compared with whites. After controlling for the applicant's educational
      background, country of origin, training, previous research awards, publication
      record, and employer characteristics, we find that black applicants remain 10
      percentage points less likely than whites to be awarded NIH research funding. Our
      results suggest some leverage points for policy intervention.

PMID- 21852499
TI  - Three periods of regulatory innovation during vertebrate evolution.
AB  - The gain, loss, and modification of gene regulatory elements may underlie a
      substantial proportion of phenotypic changes on animal lineages. To investigate
      the gain of regulatory elements throughout vertebrate evolution, we identified
      genome-wide sets of putative regulatory regions for five vertebrates, including
      humans. These putative regulatory regions are conserved nonexonic elements
      (CNEEs), which are evolutionarily conserved yet do not overlap any coding or
      noncoding mature transcript. We then inferred the branch on which each CNEE came
      under selective constraint. Our analysis identified three extended periods in the
      evolution of gene regulatory elements. Early vertebrate evolution was
      characterized by regulatory gains near transcription factors and developmental
      genes, but this trend was replaced by innovations near extracellular signaling
      genes, and then innovations near posttranslational protein modifiers.

PMID- 21852500
TI  - Rapid range shifts of species associated with high levels of climate warming.
AB  - The distributions of many terrestrial organisms are currently shifting in
      latitude or elevation in response to changing climate. Using a meta-analysis, we
      estimated that the distributions of species have recently shifted to higher
      elevations at a median rate of 11.0 meters per decade, and to higher latitudes at
      a median rate of 16.9 kilometers per decade. These rates are approximately two
      and three times faster than previously reported. The distances moved by species
      are greatest in studies showing the highest levels of warming, with average
      latitudinal shifts being generally sufficient to track temperature changes.
      However, individual species vary greatly in their rates of change, suggesting
      that the range shift of each species depends on multiple internal species traits
      and external drivers of change. Rapid average shifts derive from a wide diversity
      of responses by individual species.

PMID- 21852501
TI  - Aneuploidy drives genomic instability in yeast.
AB  - Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a
      disease of enhanced proliferative capacity. To investigate one mechanism by which
      aneuploidy could contribute to tumorigenesis, we examined the effects of
      aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry
      extra copies of single chromosomes and found that all aneuploid strains exhibited
      one or more forms of genomic instability. Most strains displayed increased
      chromosome loss and mitotic recombination, as well as defective DNA damage
      repair. Aneuploid fission yeast strains also exhibited defects in mitotic
      recombination. Aneuploidy-induced genomic instability could facilitate the
      development of genetic alterations that drive malignant growth in cancer.

PMID- 21852502
TI  - Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities
      of agonistic CD40 antibodies.
AB  - CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, is
      expressed on antigen-presenting cells (APCs) and is essential for immune
      activation. Although agonistic CD40 antibodies have been developed for
      immunotherapy, their clinical efficacy has been limited. We have found that
      coengagement of the Fc domain of agonistic CD40 monoclonal antibodies (mAbs) with
      the inhibitory Fcgamma receptor FcgammaRIIB is required for immune activation.
      Direct comparison of mAbs to CD40 enhanced for activating FcgammaR binding, hence
      capable of cytotoxicity, or for inhibitory FcgammaRIIB binding, revealed that
      enhancing FcgammaRIIB binding conferred immunostimulatory activity and
      considerably greater anti-tumor responses. This unexpected requirement for
      FcgammaRIIB in enhancing CD40-mediated immune activation has direct implications
      for the design of agonistic antibodies to TNFR as therapeutics.

PMID- 21852503
TI  - An interaction-based approach to enhancing secondary school instruction and
      student achievement.
AB  - Improving teaching quality is widely recognized as critical to addressing
      deficiencies in secondary school education, yet the field has struggled to
      identify rigorously evaluated teacher-development approaches that can produce
      reliable gains in student achievement. A randomized controlled trial of My
      Teaching Partner-Secondary--a Web-mediated approach focused on improving teacher
      student interactions in the classroom--examined the efficacy of the approach in
      improving teacher quality and student achievement with 78 secondary school
      teachers and 2237 students. The intervention produced substantial gains in
      measured student achievement in the year following its completion, equivalent to
      moving the average student from the 50th to the 59th percentile in achievement
      test scores. Gains appeared to be mediated by changes in teacher-student
      interaction qualities targeted by the intervention.

PMID- 21852504
TI  - Graduate students' teaching experiences improve their methodological research
      skills.
AB  - Science, technology, engineering, and mathematics (STEM) graduate students are
      often encouraged to maximize their engagement with supervised research and
      minimize teaching obligations. However, the process of teaching students engaged
      in inquiry provides practice in the application of important research skills.
      Using a performance rubric, we compared the quality of methodological skills
      demonstrated in written research proposals for two groups of early career
      graduate students (those with both teaching and research responsibilities and
      those with only research responsibilities) at the beginning and end of an
      academic year. After statistically controlling for preexisting differences
      between groups, students who both taught and conducted research demonstrate
      significantly greater improvement in their abilities to generate testable
      hypotheses and design valid experiments. These results indicate that teaching
      experience can contribute substantially to the improvement of essential research
      skills.

PMID- 21852506
TI  - Effectiveness of cervical hemilaminectomy in canine Hansen Type I and Type II
      disc disease: a retrospective study.
AB  - Medical records of 41 dogs, including 15 small breed dogs (<15 kg) and 26 large
      breed dogs (>15 kg), with cervical intervertebral disc disease (IVDD) that
      underwent a hemilaminectomy were reviewed. Dogs were diagnosed using myelography,
      computed tomography/myelography, or MRI, and dogs were classified as having
      either Hansen Type I disc extrusion or Hansen Type II disc protrusion located
      ventrally, ventrolaterally, or laterally within the cervical spinal canal. The
      most common clinical presentation was ambulatory tetraparesis and/or lameness
      (44%). The most affected sites for cervical IVDD were between the sixth and
      seventh cervical vertebrae (C6-C7; 78% of Hansen Type II discs) and C2-C3 (86% of
      Hansen Type I discs). Treatment was effective in 88% of dogs. Five large breed
      dogs (12%) did not improve. In dogs with a Hansen Type I disc extrusion, clinical
      signs improved in 96% of the cases. In dogs with a Hansen Type II disc
      protrusion, an excellent and good outcome was seen in 47% and 32% of cases,
      respectively. Outcome was significantly better for small breed dogs and dogs with
      Hansen Type I disc disease compared with large breed dogs and dogs with Hansen
      Type II disc disease.

PMID- 21852507
TI  - A novel method of core aspirate cytology compared to fine-needle aspiration for
      diagnosing canine osteosarcoma.
AB  - There is little information in veterinary literature regarding the diagnostic
      accuracy of aspirate cytology for the diagnosis of canine osteosarcoma (OSA). The
      authors compared the diagnostic accuracy of a novel method of cytologic
      collection, termed core aspirate cytology (CA), with fine needle aspiration (FNA)
      and histopathology in 27 dogs with lytic and/or proliferative bone lesions.
      Alkaline phosphatase (ALP) staining was performed to confirm the diagnosis of OSA
      cytologically. OSA was accurately diagnosed in 85% and 95% of FNA and CA,
      respectively. ALP staining was 100% sensitive for the diagnosis of OSA. CA using
      a bone marrow biopsy needle allowed for penetration of cortical bone and aspirate
      cytology with a larger bore needle than FNA; however, there was no significant
      difference in diagnostic accuracy between techniques. Aspirate cytology with ALP
      staining was a safe, accurate, and minimally invasive diagnostic test for the
      evaluation of suspected OSA lesions in dogs.

PMID- 21852505
TI  - Mutational inactivation of STAG2 causes aneuploidy in human cancer.
AB  - Most cancer cells are characterized by aneuploidy, an abnormal number of
      chromosomes. We have identified a clue to the mechanistic origins of aneuploidy
      through integrative genomic analyses of human tumors. A diverse range of tumor
      types were found to harbor deletions or inactivating mutations of STAG2, a gene
      encoding a subunit of the cohesin complex, which regulates the separation of
      sister chromatids during cell division. Because STAG2 is on the X chromosome, its
      inactivation requires only a single mutational event. Studying a near-diploid
      human cell line with a stable karyotype, we found that targeted inactivation of
      STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid
      human glioblastoma cell lines, targeted correction of the endogenous mutant
      alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption
      of cohesin is a cause of aneuploidy in human cancer.

PMID- 21852508
TI  - Palliative radiation therapy in the treatment of canine appendicular synovial
      sarcoma.
AB  - Synovial sarcoma is a rare tumor in dogs, occurring in approximately 27% of
      neoplasms involving joints, with the elbow representing a common site of
      occurrence. The recommended treatment of canine synovial sarcoma is amputation.
      The authors describe the use of palliative radiation therapy for the treatment of
      synovial sarcoma involving the elbow of a dog and conclude that this treatment
      modality may have use in some patients affected with synovial sarcoma.

PMID- 21852509
TI  - Concurrent splenic and right atrial mass at presentation in dogs with HSA: a
      retrospective study.
AB  - The objective of this retrospective study was to evaluate the presence of
      concurrent splenic and cardiac hemangiosarcoma (HSA). Dogs were divided into two
      groups: group 1 included 23 dogs with splenic HSA, and group 2 included 31 dogs
      with a cardiac HSA. All dogs were fully assessed for metastasis with thoracic
      radiography, abdominal and/or cardiac ultrasound, and/or postmortem examination.
      Two dogs (8.7%) in group 1 had a concurrent cardiac mass. Neither of these dogs
      had pericardial effusion, and both were golden retrievers. Thirteen of the dogs
      in group 1 presented with a hemoabdomen. Concurrent intra-abdominal metastasis
      was noted in seven dogs. In group 2, 9/31 (29%) of the dogs had a concurrent
      splenic HSA, and 13/31 (42%) of the dogs had evidence of metastasis to another
      site. There was a significant association between age and the presence of
      nonsplenic metastasis (odds ratio, 0.457). The rate of concurrent right atrial
      mass detected by cardiac ultrasound in dogs with splenic HSA was 8.7%, which is
      less than previously reported. For dogs with right atrial HSA, the risk of
      metastasis to nonsplenic sites decreases with age.

PMID- 21852510
TI  - Nasal hydropulsion: a novel tumor biopsy technique.
AB  - Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge
      for small animal practitioners. Multiple nasal biopsy techniques have been
      described in the past. This report describes a simplified flushing technique to
      biopsy and debulk nasal tumors, which often also results in immediate clinical
      relief for the patient. Based on the results of this retrospective study, the
      authors recommend high-pressure saline hydropulsion as a minimally invasive
      diagnostic, and potentially therapeutic, technique for nasal tumors in dogs and
      cats.

PMID- 21852511
TI  - Pets in the family: practical approaches.
AB  - Adapting family life cycle theory to include pets provides veterinarians with a
      framework for understanding and reinforcing the human-animal bond. The family
      genogram with pets is a practice tool that identifies all people and pets in the
      family, enhancing the practice of One Health at the community level.

PMID- 21852512
TI  - BAER testing in a dog with bilateral external ear canal atresia.
AB  - A 3 yr old male castrated Labrador retriever presented for evaluation and
      treatment of bilateral atresia of the external ear canals. The owners reported
      that the dog could hear only loud and high-pitched noises. Computed tomography of
      the head revealed intact vertical and horizontal ear canals filled with debris
      and a debris-filled right tympanic bulla. Air- and bone-conducted brainstem
      auditory evoked response (BAER) testing revealed an elevated response threshold
      to air-conducted stimuli and greater amplitude waveforms evoked by bone-conducted
      stimuli. The ear canals were surgically corrected via lateral ear canal
      resection. BAER testing postoperatively revealed a decrease in the air-conducted
      BAER threshold. This case is an example of the use of bone-conducted BAER testing
      to aid in the diagnosis of conductive deafness, and in determining prognosis for
      normal hearing after surgical treatment of external ear canal atresia.

PMID- 21852513
TI  - Partial resolution of hypoplastic trachea in six english bulldog puppies with
      bronchopneumonia.
AB  - Six English bulldog and nine nonbrachycephalic puppies with bronchopneumonia and
      radiographs were evaluated. Relative size of the trachea was measured by the
      tracheal diameter (TD) and the thoracic inlet distance (TI), expressed as a ratio
      (TD:TI). At diagnosis of bronchopneumonia, there was a significant difference
      between the median TD:TI of the bulldog puppies (0.07; range, 0.06-0.09) and that
      of the nonbrachycephalic puppies (0.14; range, 0.11-0.25; P=0.0004). At the same
      time, there was also a significant difference between the mean TD:TI of bulldog
      puppies (0.07+/-0.01) and that of nonbrachycephalic puppies (0.15+/-0.05;
      P=0.002). Follow-up radiographs showed significant increases in TD:TI ratio in
      all six bulldogs (median TD:TI = 0.14; range, 0.12-0.18; P=0.03 and mean TD:TI =
      0.15+/-0.02; P=0.0007), whereas the ratio did not change significantly in the
      nonbrachycephalic control group (median TD:TI = 0.17; range, 0.14-0.22; P=0.10
      and mean TD:TI = 0.18+/-0.03; P=0.06). Tracheal hypoplasia in some brachycephalic
      dogs might partially or completely resolve with growth to mature body size.

PMID- 21852514
TI  - Amlodipine-induced gingival hyperplasia in a Great Dane.
AB  - A 3 yr old, 70 kg (154 lbs) female spayed Great Dane developed gingival
      hyperplasia after treatment of systemic hypertension with amlodipine 7.5 mg q 12
      hr for 16 mo. Physical examination was unremarkable except for systemic
      hypertension and severe gingival hyperplasia. Amlodipine was replaced with
      hydralazine (0.72 mg/kg [0.32 mg/lb]). Nine months later, gingival hyperplasia
      was nearly resolved and hypertension was well controlled. Calcium channel
      blockers such as amlodipine are a rare cause of gingival hyperplasia in the
      canine patient. Recognition of this side effect is important because a full
      recovery can be achieved when the offending agent is removed.

PMID- 21852515
TI  - Pseudallescheria boydii species complex fungal rhinitis and sinusitis in a dog.
AB  - A 9 yr old male castrated Australian shepherd mixed-breed dog with a 3 mo history
      of intermittent unilateral epistaxis was diagnosed with Pseudallescheria boydii
      species complex fungal rhinitis and sinusitis. This fungal organism is a rare
      cause of disease in dogs and an emerging human pathogen. The dog was successfully
      treated with topical clotrimazole.

PMID- 21852516
TI  - Canine and feline epileptic seizures and the lunar cycle: 2,507 seizures (2000
      2008).
AB  - Epileptic seizures in 211 canine and feline patients diagnosed with idiopathic
      epilepsy were evaluated for temporal significance in relation to the lunar cycle.
      Seizure counts were compared among each of the eight individual lunar phases,
      among each of eight exact lunar phase dates, and by percent of lunar illumination
      using generalized estimating equations. No statistical significance was found in
      any of these comparisons excluding a relationship between the onset of epileptic
      seizures and the phases of the moon. Alteration in anticonvulsant treatment or
      monitoring of canine and feline patients with idiopathic epilepsy at large was
      not warranted based on the lunar cycle.

PMID- 21852517
TI  - Mycotic mastitis in three dogs due to Blastomyces dermatitidis.
AB  - Canine blastomycosis is a common systemic fungal infection within the Ohio and
      Mississippi River valleys and typically presents as pneumonia, lymphadenitis, or
      endophthalmitis. This report describes three cases in which mammary tissue
      samples were submitted to the Department of Pathobiology, University of
      Tennessee, College of Veterinary Medicine with clinical suspicion of neoplasia or
      postpartum bacterial mastitis. Pyogranulomatous to granulomatous mastitis and
      dermatitis with intralesional yeast consistent with Blastomyces dermatitidis were
      diagnosed. Two of the three dogs also had lymph node and pulmonary involvement.
      Mycotic mastitis due to Blastomyces dermatitidis is rarely reported and
      blastomycosis should be considered in the differential diagnosis of dogs with
      mammary lesions from endemic areas.

PMID- 21852518
TI  - Spontaneous urethral catheter kinking or knotting in male dogs: four cases.
AB  - Four dogs were diagnosed with urethral catheter malfunction. The catheter was
      kinked in three dogs and knotted in one dog. In two dogs, kinking of the catheter
      was associated with presence of urethroliths in the perineal urethra. Diagnosis
      was based on the difficulty encountered retrieving the catheter in all dogs and
      swelling in the scrotal or perineal area in two dogs. Diagnosis of catheter
      kinking or knotting was confirmed after catheter retrieval. Catheter removal was
      achieved in two dogs after traction under anesthesia, whereas scrotal or perineal
      urethrotomy were used in the other two dogs. No complications associated with
      urination were reported in any of the dogs after 7 to 12 mo.

PMID- 21852519
TI  - Physical activity benefits of learning to ride a two-wheel bicycle for children
      with Down syndrome: a randomized trial.
AB  - BACKGROUND: People with Down syndrome (DS) display consistent patterns of
      physical inactivity. If these sedentary behaviors continue over extended periods
      of time, there will be negative health consequences. OBJECTIVE: The objective of
      this study was to investigate the physical activity and health-related outcomes
      of teaching children with DS to ride a 2-wheel bicycle. DESIGN: This study was a
      randomized intervention in which the control group waited 1 year to receive the
      intervention. SETTING: This intervention study was conducted in a community
      setting. PARTICIPANTS: The participants were children who were 8 to 15 years of
      age and who had been diagnosed with DS. Intervention The participants were
      randomly assigned to an experimental group (bicycle intervention) or a control
      group (no intervention). MEASUREMENTS: Measurements were obtained in the month
      before the intervention (preintervention), at 7 weeks after the intervention, and
      at 12 months after the preintervention measurement for all participants. RESULTS:
      The results indicated no group differences at the preintervention session. Fifty
      six percent of the participants in the experimental group successfully learned to
      ride a 2-wheel bicycle during the 5-day intervention. Analysis showed that
      participants who learned to ride spent significantly less time in sedentary
      activity at 12 months after the preintervention measurement and more time in
      moderate to vigorous physical activity than participants in the control group.
      Body fat appeared to be positively influenced over time in participants who
      learned to ride. LIMITATIONS: It is unknown how frequently the children in the
      experimental group rode their bicycles after the intervention. CONCLUSIONS: Most
      children who are 8 to 15 years of age and who have been diagnosed with DS can
      learn to ride a 2-wheel bicycle. Learning to ride can reduce time spent in
      sedentary activity and increase time spent in moderate to vigorous physical
      activity, which may influence the health and functioning of these children.

PMID- 21852520
TI  - The Low Back Activity Confidence Scale (LoBACS): preliminary validity and
      reliability.
AB  - BACKGROUND: Low back pain affects a substantial number of adults each year and is
      persistent or recurrent for many. Self-efficacy is an important predictor of
      functional recovery. OBJECTIVE: The purpose of this investigation was to assess
      the preliminary reliability and validity of the Low Back Activity Confidence
      Scale (LoBACS) for individuals with histories of low back pain or lumbar surgery.
      DESIGN: Two overlapping samples of patients who had undergone a microdiskectomy
      participated: a test-retest sample of 21 individuals and a validity sample of 53
      individuals. METHODS: Low Back Activity Confidence Scale items pertaining to self
      efficacy for functional activities (FnSE subscale), self-regulation of back
      health (Self-RegSE subscale), and regular exercise (ExSE subscale) were generated
      from existing literature and clinical observations. The test-retest sample
      completed the LoBACS twice, approximately 10 days apart. The validity sample
      completed the LoBACS and measures of functional performance, self-reported
      leisure and occupational physical activity, pain, fear beliefs, disability, and
      quality of life. RESULTS: The FnSE, Self-RegSE, and ExSE subscale scores and
      LoBACS total score had excellent to acceptable test-retest reliability
      (intraclass correlation coefficients of .924, .634, .710, and .850, respectively)
      and internal consistency (Cronbach alpha coefficients of .924, .804, .941, and
      .911, respectively). The LoBACS subscales were correlated in expected directions
      with physical performance, physical activity, pain, fear beliefs, disability, and
      quality of life, providing initial evidence of concurrent validity. CONCLUSIONS:
      The findings provide preliminary content and concurrent validity and interrater
      and internal consistency reliability for the LoBACS measure of self-efficacy for
      individuals with histories of low back pain and lumbar microdiskectomy.

PMID- 21852521
TI  - Lethality and pathogenesis of airborne infection with filoviruses in A129
      alpha/beta -/- interferon receptor-deficient mice.
AB  - Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There
      are therefore two strategies available to establish a murine model of filovirus
      infection: adaptation of the virus to the host or the use of genetically modified
      mice that are susceptible to the virus. A number of knockout (KO) strains of mice
      with defects in either their adaptive or innate immunity are susceptible to non
      adapted filoviruses. In this study, A129 alpha/beta -/- interferon receptor
      deficient KO mice, strain A129 IFN-alpha/beta -/-, were used to determine the
      lethality of a range of filoviruses, including Lake Victoria marburgvirus (MARV),
      Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV) and
      Cote d'Ivoire ebolavirus (CIEBOV), administered by using intraperitoneal (IP) or
      aerosol routes of infection. One hundred percent mortality was observed in all
      groups of KO mice that were administered with a range of challenge doses of MARV
      and ZEBOV by either IP or aerosol routes. Mean time to death for both routes was
      dose-dependent and ranged from 5.4 to 7.4 days in the IP injection challenge, and
      from 10.2 to 13 days in the aerosol challenge. The lethal dose (50 % tissue
      culture infective dose, TCID(50)) of ZEBOV for KO mice was <1 TCID(50) ml(-1)
      when administered by either the IP or aerosol route of infection; for MARV the
      lethal dose was <1 TCID(50) ml(-1) by the IP route of infection and <10 TCID(50)
      ml(-1) by the aerosol route. In contrast, there was no mortality after infection
      with SEBOV or REBOV by either IP or aerosol routes of infection; all the mice
      lost weight (~15 % loss of group mean body weight with SEBOV and ~7 % with REBOV)
      but recovered to their original weights by day 14 post-challenge. There was no
      mortality in mice administered with CIEBOV via the IP route of infection and no
      clinical signs of infection were observed. The progression of disease was faster
      following infection with ZEBOV than with MARV but ultimately both viruses caused
      widespread infection with high titres of the infectious viruses in multiple
      organs. Histopathological observations were consistent with other animal models
      and showed widespread organ damage. This study suggests that MARV and ZEBOV are
      more virulent when administered via the IP route rather than by aerosol
      infection, although both are highly virulent by either route. The KO mouse may
      provide a useful model to test potential antiviral therapeutics against wild-type
      filoviruses.

PMID- 21852522
TI  - Screening for novel quorum-sensing inhibitors to interfere with the formation of
      Pseudomonas aeruginosa biofilm.
AB  - The objective of this study was to screen for novel quorum-sensing inhibitors
      (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm
      formation. Six of 46 active components found in TCMs were identified as putative
      QSIs based on molecular docking studies. Of these, three compounds inhibited
      biofilm formation by Pseudomonas aeruginosa and Stenotrophomonas maltophilia at a
      concentration of 200 uM. A fourth compound (emodin) significantly inhibited
      biofilm formation at 20 uM and induced proteolysis of the quorum-sensing signal
      receptor TraR in Escherichia coli at a concentration of 3-30 mM. Emodin also
      increased the activity of ampicillin against P. aeruginosa. Therefore, emodin
      might be suitable for development into an antivirulence and antibacterial agent.

PMID- 21852523
TI  - Detection and characterization of antibiotic-resistance genes in Arcanobacterium
      pyogenes strains from abscesses of forest musk deer.
AB  - Arcanobacterium pyogenes is commonly isolated from ruminant animals as an
      opportunistic pathogen that co-infects with other bacteria, normally causing
      surface or internal abscesses. Twenty-eight strains of A. pyogenes isolated from
      forest musk deer suppurative samples were identified by their 16S rRNA gene
      sequences, and confirmed by amplification of the pyolysin-encoding gene (plo) in
      all isolates. The MICs of 14 commonly used antibiotics were determined by an agar
      dilution method. Class 1 and 2 intI genes were amplified to determine whether
      integrons were present in the A. pyogenes genome. Class 1 gene cassettes were
      detected by specific primers and analysed by sequencing. All of the strains were
      susceptible to most fluoroquinolone antibiotics; however, high resistance rates
      were observed for beta-lactams and trimethoprim. A total of 18 of the isolates
      (64.3%) were positive for the class 1 intI gene, and 16 (57.1%) contained class 1
      gene cassettes with the aacC, aadA1, aadA2, blaP1 and dfr2a genes. Most were
      present in the multi-resistant isolates, indicating a general concordance between
      the presence of gene cassettes and antibiotic resistance, and that the integrons
      have played an important role in the dissemination of antimicrobial resistance in
      this species.

PMID- 21852524
TI  - Prevalence of virulence genes in Escherichia coli strains isolated from piglets
      in the suckling and weaning period in Mexico.
AB  - Faecal Escherichia coli isolates from suckling (n = 503) and weaning (n = 450)
      piglets with and without diarrhoea from 10 farms in Mexico were examined for
      identification and prevalence of virulence genes. E. coli isolates were tested
      further for enterotoxin (LT, STa, STb, Stx1, Stx2 and EAST1), fimbrial (F4, F5,
      F6, F17, F18 and F41) and eae adhesin genes by multiplex PCR. Of the 953 isolates
      of E. coli examined by multiplex PCR, 650 (68.2 %) isolates were positive for at
      least one adhesin gene. Among the isolates from diarrhoeic piglets, F41 (72 %)
      was the most prevalent adhesin followed by eae adhesin (27 %), F6 (12 %), F17 (9
      %), F18 (9 %), F5 (8 %) and F4 (3 %). Enterotoxin genes were detected in 424
      (44.5 %) of the isolates, of which EAST1 (38 %) and STa (30 %) were the most
      common, followed by STb (17 %), Stx2 (6 %) and LT (5 %). Twenty-three per cent of
      isolates from suckling piglets and 43 % of isolates from weaned piglets carried
      both enterotoxin and adhesin genes, the most common virotypes being F41 : STa,
      F41 : EAST1, EAST1 : eae, F41 : F6, F41 : STa : STb, F41 : eae and F17 : eae. The
      present study examined for the first time, to our knowledge, the prevalence of 13
      virulence genes among E. coli strains isolated from piglets with and without
      diarrhoea in Mexico. The results suggested that there are a wide variety of
      virulence genes associated with diarrhoea in piglets. This study provides
      baseline information on the significance of specific virotypes associated with
      suckling and weaning periods in piglets in Mexico.

PMID- 21852525
TI  - Changes in antimicrobial susceptibility and major clones of Acinetobacter
      calcoaceticus-baumannii complex isolates from a single hospital in Korea over 7
      years.
AB  - Acinetobacter species have emerged as opportunistic nosocomial pathogens in
      intensive care units. Epidemic spread and outbreaks of multidrug-resistant or
      carbapenem-resistant Acinetobacter baumannii infections have been described
      worldwide. Species distribution, antimicrobial resistance and genotypes were
      investigated for Acinetobacter species isolates collected from a single
      institution in Korea over 7 years. Two hundred and eighty-seven Acinetobacter
      species isolates were collected from patients with bloodstream infections in one
      Korean hospital from 2003 to 2010. Most of them belonged to the Acinetobacter
      calcoaceticus-baumannii complex (94.4 %). The most frequently isolated species
      was A. baumannii (44.2 %), followed by Acinetobacter nosocomialis (formerly
      Acinetobacter genomic species 13TU) (34.1 %). The proportion of A. baumannii
      increased significantly from 2008 to 2010 (40.4 to 50.0 %). From 2008, imipenem
      and meropenem resistance rates increased significantly compared with 2003-2007
      (12.9 % and 20.5 %, respectively, to 41.4 % and 41.5 %, respectively). An
      increased carbapenem resistance rate between the two periods was identified more
      clearly amongst A. baumannii isolates. Polymyxin-resistant A. baumannii isolates
      emerged in 2008-2010, despite the availability of few isolates. The increase of
      carbapenem resistance in A. baumannii might be due to the substitution of main
      clones. Although ST92 and ST69 were the most prevalent clones amongst A.
      baumannii in 2003-2007 (47.8 % and 15.9 %, respectively), ST75 and ST138 had
      increased in 2008-2010 (39.7 % and 25.9 %, respectively). Although ST92 showed
      moderate resistance to carbapenems, most ST75 and ST138 isolates were resistant
      to carbapenems. All ST75 and ST138 isolates, but only one ST92 isolate, contained
      the bla(OXA-23-like) gene. Increased carbapenem resistance in Acinetobacter
      species and A. baumannii isolates might be due to the expansion of specific
      carbapenem-resistant clones.

PMID- 21852526
TI  - Characterization of pathogenicity island prophage in clinical and environmental
      strains of Vibrio cholerae.
AB  - In this study 86 isolates of Vibrio cholerae were analysed for their adhesive
      properties and the presence of pathogenicity island genes. With the exception of
      three isolates, all of the other clinical isolates (92.5%) contained an intact
      TCP (toxin-co-regulated pilus) gene cluster. In contrast, 95% of all
      environmental non-O1-non-O139 isolates were negative for the TCP gene cluster.
      The majority of clinical isolates (82.5%) possessed the complete vibrio
      pathogenicity island (VPI) gene cluster and had a similar RFLP pattern, while
      only a single environmental strain possessed an almost complete VPI cluster
      (lacking 0.4 kb in the tcpA and toxT region). The result showed that the isolates
      with tcpA(+)/toxT(+) had a strong attachment for HT-29 and Vero cells, whereas
      isolates with tcpA(+)/toxT(-) or tcpA(-)/toxT(-) genomic characteristics showed
      no autoagglutination and weak attachment for the cell lines. Two environmental
      strains (tcpA(-)/toxT(-)) showed strong adhesive properties to the cell lines,
      indicating that non-fimbrial adhesive factors are involved in the environmental
      V. cholerae strains in the absence of TCP.

PMID- 21852527
TI  - Comparison of minimum inhibitory concentration by broth microdilution testing
      versus standard disc diffusion testing in the detection of penicillin,
      erythromycin and ciprofloxacin resistance in viridans group streptococci.
AB  - The aim of this study was to investigate the reliability of disc diffusion
      testing with penicillin, erythromycin and ciprofloxacin within the viridans group
      streptococci (VGS). In total, the antibiotic susceptibilities of 167 VGS isolates
      were compared by standard disc diffusion and broth microdilution methods, and
      these phenotypic data were compared to the carriage of the respective gene
      resistance determinants [ermB and mefA/E (macrolides); QRDR, gyrA, gyrB, parC and
      parE (quinolones)]. Overall, there were 35 discrepancies [resistant by MIC and
      susceptible by zone diameter (21.0%)] between MIC and disc diameter when
      penicillin susceptibility was interpreted by Clinical and Laboratory Standards
      Institute criteria. Scattergrams showed a bimodal distribution between non
      susceptible and susceptible strains when erythromycin susceptibility was tested
      by both methods. Thirty-four (20.4%) isolates were categorized as resistant by
      MIC breakpoints, while disc diameter defined these as having intermediate
      resistance. With ciprofloxacin, three isolates (1.8%) showed minor discrepancies
      between MIC breakpoints and disc diameter. Isolates non-susceptible to all three
      antimicrobial agents tested were reliably distinguished from susceptible isolates
      by disc diffusion testing, except for the detection of low-level resistance to
      penicillin, where broth microdilution or an alternative quantitative MIC method
      should be used. Otherwise, we conclude that disc diffusion testing is a reliable
      method to detect strains of VGS non-susceptible to penicillin, erythromycin and
      ciprofloxacin, as demonstrated with their concordance to their gene resistance
      characteristics.

PMID- 21852528
TI  - A CD46 transgenic mouse model for studying the histopathology of arthritis caused
      by subcutaneous infection with Streptococcus dysgalactiae subspecies equisimilis.
AB  - Ankle arthritis was induced by a single subcutaneous (s.c.) infection of 1*10(7)
      c.f.u. of the Streptococcus dysgalactiae subspecies equisimilis strain RE378,
      which was isolated from a patient suffering from multiple organ failure due to
      septicaemia, into both hind footpads of human CD46-expressing transgenic (Tg)
      mice. In contrast, in non-Tg mice, the incipient foot lesions (swelling and
      redness) resolved before arthritis developed. The number of viable bacteria in
      tissue samples and the arthritis frequency on days 3 and 28 after infection were
      higher in CD46 Tg mice than in non-Tg mice. The histopathological findings in the
      hind ankle sections of CD46 Tg mice showed the stimulation of osteoclast
      formation associated with inflammation of the synovial membrane and the
      development of aggressive granulation tissue (pannus). In addition, increased
      expression levels of interleukin (IL)-6, receptor activator of NF-kappaB ligand,
      IL-1beta and tumour necrosis factor alpha were detected in the foot bones of CD46
      Tg mice but not in those of non-Tg mice. These observations suggest that the s.c.
      infection with S. dysgalactiae subsp. equisimilis induced arthritis in the ankle
      joints of CD46 Tg mice as a consequence of the prolonged inflammation associated
      with focal bone loss.

PMID- 21852529
TI  - Brain abscess caused by Cladophialophora bantiana in China.
AB  - A case of a 38-year-old male farmer with a brain abscess caused by
      Cladophialophora bantiana is described. He had a 2 year history of non-insulin
      dependent diabetes and myelodysplastic syndrome. A cranial computed tomography
      scan demonstrated a hypodense ring lesion with peripheral oedema and a midline
      shift in the left frontal lobe. A darkly pigmented mould was isolated from the
      brain abscess. The isolate was identified as C. bantiana based on its
      morphological features and DNA sequence analysis. The patient was unresponsive to
      burr hole aspiration and irrigation, as well as liposomal amphotericin B
      infusion, and died after discharge from the hospital. This is believed to be the
      first case of a cerebral abscess due to C. bantiana in China.

PMID- 21852530
TI  - Treatment of chronic pulmonary blastomycosis with caspofungin.
AB  - Current practice guidelines recommend that pulmonary blastomycosis be treated
      with antifungal agents such as amphotericin B and itraconazole. Echinocandins are
      not recommended because of poor in vitro activity against Blastomyces
      dermatitidis and lack of supporting clinical data. We report a case of chronic
      pulmonary blastomycosis treated successfully with caspofungin.

PMID- 21852531
TI  - miR than meets the eye.
AB  - Retinoblastoma is a rare pediatric cancer that has served as a paradigm to
      investigate the mechanisms of tumorigenesis. In this issue of Genes &
      Development, Conkrite and colleagues (pp. 1734-1745) found high levels of the miR
      17~92 and miR-106b-25 microRNAs in primary retinoblastomas and show that
      overexpression of miR-17~92 accelerates retinoblastoma development in mice by
      promoting proliferation, in part by reducing expression of the cell cycle
      inhibitor p21. These experiments identify the RB/miR-17~92/p21 axis as a critical
      regulator of retinoblastoma tumorigenesis and potentially many other cancers.

PMID- 21852532
TI  - LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network
      for digestive function.
AB  - We have determined the cistrome and transcriptome for the nuclear receptor liver
      receptor homolog-1 (LRH-1) in exocrine pancreas. Chromatin immunoprecipitation
      (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of
      genes encoding digestive enzymes and secretory and mitochondrial proteins. LRH-1
      cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in
      regulating exocrine pancreas-specific gene expression. Elimination of LRH-1 in
      adult mice reduced the concentration of several lipases and proteases in
      pancreatic fluid and impaired pancreatic fluid secretion in response to
      cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific
      transcriptional network required for the production and secretion of pancreatic
      fluid.

PMID- 21852533
TI  - Context-specific alpha- to-beta-cell reprogramming by forced Pdx1 expression.
AB  - Using single transcription factors to reprogram cells could produce important
      insights into the epigenetic mechanisms that direct normal differentiation, or
      counter inappropriate plasticity, or even provide new ways of manipulating normal
      ontogeny in vitro to control lineage diversification and differentiation. We
      enforced Pdx1 expression from the Neurogenin-3-expressing endocrine commitment
      point onward and found during the embryonic period a minor increased beta-cell
      allocation with accompanying reduced alpha-cell numbers. More surprisingly,
      almost all remaining Pdx1-containing glucagon/Arx-producing cells underwent a
      fairly rapid conversion at postnatal stages, through glucagon-insulin double
      positivity, to a state indistinguishable from normal beta cells, resulting in
      complete alpha-cell absence. This alpha-to-beta conversion was not caused by
      activating Pdx1 in the later glucagon-expressing state. Our findings reveal that
      Pdx1 can work single-handedly as a potent context-dependent autonomous
      reprogramming agent, and suggest a postnatal differentiation evaluation stage
      involved in normal endocrine maturation.

PMID- 21852534
TI  - RNAi-independent role for Argonaute2 in CTCF/CP190 chromatin insulator function.
AB  - A major role of the RNAi pathway in Schizosaccharomyces pombe is to nucleate
      heterochromatin, but it remains unclear whether this mechanism is conserved. To
      address this question in Drosophila, we performed genome-wide localization of
      Argonaute2 (AGO2) by chromatin immunoprecipitation (ChIP)-seq in two different
      embryonic cell lines and found that AGO2 localizes to euchromatin but not
      heterochromatin. This localization pattern is further supported by
      immunofluorescence staining of polytene chromosomes and cell lines, and these
      studies also indicate that a substantial fraction of AGO2 resides in the nucleus.
      Intriguingly, AGO2 colocalizes extensively with CTCF/CP190 chromatin insulators
      but not with genomic regions corresponding to endogenous siRNA production.
      Moreover, AGO2, but not its catalytic activity or Dicer-2, is required for
      CTCF/CP190-dependent Fab-8 insulator function. AGO2 interacts physically with
      CTCF and CP190, and depletion of either CTCF or CP190 results in genome-wide loss
      of AGO2 chromatin association. Finally, mutation of CTCF, CP190, or AGO2 leads to
      reduction of chromosomal looping interactions, thereby altering gene expression.
      We propose that RNAi-independent recruitment of AGO2 to chromatin by insulator
      proteins promotes the definition of transcriptional domains throughout the
      genome.

PMID- 21852535
TI  - Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi
      reactivation in mice.
AB  - The noncoding Tsix RNA is an antisense repressor of Xist and regulates X
      inactivation in mice. Tsix is essential for preventing the inactivation of the
      maternally inherited X chromosome in extraembryonic lineages where imprinted X
      chromosome inactivation (XCI) occurs. Here we establish an inducible Tsix
      expression system for investigating Tsix function in development. We show that
      Tsix has a clear functional window in extraembryonic development. Within this
      window, Tsix can repress Xist, which is accompanied by DNA methylation of the
      Xist promoter. As a consequence of Xist repression, reactivation of the inactive
      X chromosome (Xi) is widely observed. In the parietal endoderm, Tsix represses
      Xist and causes reactivation of an Xi-linked GFP transgene throughout
      development, whereas Tsix progressively loses its Xist-repressing function from
      embryonic day 9.5 (E9.5) onward in trophoblast giant cells and
      spongiotrophoblast, suggesting that Tsix function depends on a lineage-specific
      environment. Our data also demonstrate that the maintenance of imprinted XCI
      requires Xist expression in specific extraembryonic tissues throughout
      development. This finding shows that reversible XCI is not exclusive to
      pluripotent cells, and that in some lineages cell differentiation is not
      accompanied by a stabilization of the Xi.

PMID- 21852536
TI  - Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell
      proliferation.
AB  - Loss of extracellular matrix (ECM) attachment leads to metabolic impairments that
      limit cellular energy production. Characterization of the metabolic alterations
      induced by ECM detachment revealed a dramatic decrease in uptake of glucose,
      glutamine, and pyruvate, and a consequent decrease in flux through glycolysis,
      the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle. However,
      flux through pyruvate dehydrogenase (PDH) is disproportionally decreased,
      concomitant with increased expression of the PDH inhibitory kinase, PDH kinase 4
      (PDK4), and increased carbon secretion. Overexpression of ErbB2 maintains PDH
      flux by suppressing PDK4 expression in an Erk-dependent manner, and Erk signaling
      also regulates PDH flux in ECM-attached cells. Additionally, epidermal growth
      factor (EGF), a potent inducer of Erk, positively regulates PDH flux through
      decreased PDK4 expression. Furthermore, overexpression of PDK4 in ECM-detached
      cells suppresses the ErbB2-mediated rescue of ATP levels, and in attached cells,
      PDK4 overexpression decreases PDH flux, de novo lipogenesis, and cell
      proliferation. Mining of microarray data from human tumor data sets revealed that
      PDK4 mRNA is commonly down-regulated in tumors compared with their tissues of
      origin. These results identify a novel mechanism by which ECM attachment, growth
      factors, and oncogenes modulate the metabolic fate of glucose by controlling PDK4
      expression and PDH flux to influence proliferation.

PMID- 21852538
TI  - Calsenilin regulates presenilin 1/gamma-secretase-mediated N-cadherin epsilon
      cleavage and beta-catenin signaling.
AB  - Presenilin 1 (PS1) is a component of the gamma-secretase complex that cleaves a
      variety of type I membrane proteins, including the beta-amyloid precursor protein
      (beta-APP), Notch, and neuronal (N)- and epithelial (E)-cadherins. N-cadherin is
      an essential adhesion molecule that forms a complex with, and is cleaved by,
      PS1/gamma-secretase and beta-catenin in the plasma membrane. The purpose of this
      study was to determine whether calsenilin, a presenilin-interacting protein, has
      a functional role in PS1/gamma-secretase-mediated N-cadherin epsilon-cleavage
      using Western blot analysis, RT-PCR, immunoprecipitation, subcellular
      fractionation, biotinylation, and a luciferase reporter assay in SH-SY5Y
      neuroblastoma cells. Here, we demonstrate that the expression of calsenilin leads
      to a disruption of PS1/gamma-secretase-mediated epsilon-cleavage of N-cadherin,
      which results in the significant accumulation of N-cadherin C-terminal fragment 1
      (Ncad/CTF1), the reduction of cytoplasmic Ncad/CTF2 release, and a deceleration
      of PS1-CTF delivery to the cell surface. Interestingly, we also found that the
      expression of calsenilin is associated with the redistribution of beta-catenin
      from the cell surface to a cytoplasmic pool, as well as with the negative
      regulation of genes that are targets of T-cell factor/beta-catenin nuclear
      signaling. Taken together, our findings suggest that calsenilin is a novel
      negative regulator of N-cadherin processing that plays an important role in beta
      catenin signaling.

PMID- 21852537
TI  - Validation of MdmX as a therapeutic target for reactivating p53 in tumors.
AB  - MdmX, also known as Mdm4, is a critical negative regulator of p53, and its
      overexpression serves to block p53 tumor suppressor function in many cancers.
      Consequently, inhibiting MdmX has emerged as an attractive approach to restoring
      p53 function in those cancers that retain functional p53. However, the
      consequences of acute systemic MdmX inhibition in normal adult tissues remain
      unknown. To determine directly the effects of systemic MdmX inhibition in normal
      tissues and in tumors, we crossed mdmX(-/-) mice into the p53ER(TAM) knockin
      background. In place of wild-type p53, p53ER(TAM) knockin mice express a variant
      of p53, p53ER(TAM), that is completely dependent on 4-hydroxy-tamoxifen for its
      activity. MdmX inhibition was then modeled by restoring p53 function in these
      MdmX-deficient mice. We show that MdmX is continuously required to buffer p53
      activity in adult normal tissues and their stem cells. Importantly, the effects
      of transient p53 restoration in the absence of MdmX are nonlethal and reversible,
      unlike transient p53 restoration in the absence of Mdm2, which is ineluctably
      lethal. We also show that the therapeutic impact of restoring p53 in a tumor
      model is enhanced in the absence of MdmX, affording a significant extension of
      life span over p53 restoration in the presence of MdmX. Hence, systemic
      inhibition of MdmX is both a feasible therapeutic strategy for restoring p53
      function in tumors that retain wild-type p53 and likely to be significantly safer
      than inhibition of Mdm2.

PMID- 21852539
TI  - Anthrax infection.
AB  - Bacillus anthracis infection is rare in developed countries. However, recent
      outbreaks in the United States and Europe and the potential use of the bacteria
      for bioterrorism have focused interest on it. Furthermore, although anthrax was
      known to typically occur as one of three syndromes related to entry site of
      (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including
      severe soft tissue infection in injectional drug users is emerging. Although
      shock has been described with cutaneous anthrax, it appears much more common with
      gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the
      United States), and injectional anthrax. Based in part on case series, the
      estimated mortalities of cutaneous, gastrointestinal, inhalational, and
      injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific
      early symptomatology makes initial identification of anthrax cases difficult.
      Clues to anthrax infection include history of exposure to herbivore animal
      products, heroin use, or clustering of patients with similar respiratory symptoms
      concerning for a bioterrorist event. Once anthrax is suspected, the diagnosis can
      usually be made with Gram stain and culture from blood or surgical specimens
      followed by confirmatory testing (e.g., PCR or immunohistochemistry). Although
      antibiotic therapy (largely quinolone-based) is the mainstay of anthrax
      treatment, the use of adjunctive therapies such as anthrax toxin antagonists is a
      consideration.

PMID- 21852540
TI  - Sarcoidosis blood transcriptome reflects lung inflammation and overlaps with
      tuberculosis.
AB  - RATIONALE: Sarcoidosis is a granulomatous disease of unknown etiology, although
      M. tuberculosis may play a role in the pathogenesis. The traditional view holds
      that inflammation in sarcoidosis is compartmentalized to involved organs.
      OBJECTIVES: To determine whether whole blood gene expression signatures reflect
      inflammatory pathways in the lung in sarcoidosis and whether these signatures
      overlap with tuberculosis. METHODS: We analyzed transcriptomic data from blood
      and lung biopsies in sarcoidosis and compared these profiles with blood
      transcriptomic data from tuberculosis and other diseases. MEASUREMENTS AND MAIN
      RESULTS: Applying machine learning algorithms to blood gene expression data, we
      built a classifier that distinguished sarcoidosis from health in derivation and
      validation cohorts (92% sensitivity, 92% specificity). The most discriminative
      genes were confirmed by quantitative PCR and correlated with disease severity.
      Transcript profiles significantly induced in blood overlapped with those in lung
      biopsies and identified shared dominant inflammatory pathways (e.g., Type-I/II
      interferons). Sarcoidosis and tuberculosis shared more overlap in blood gene
      expression compared with other diseases using the 86-gene signature reported to
      be specific for tuberculosis and the sarcoidosis signature presented herein,
      although reapplication of machine learning algorithms could identify genes
      specific for sarcoidosis. CONCLUSIONS: These data indicate that blood
      transcriptome analysis provides a noninvasive method for identifying inflammatory
      pathways in sarcoidosis, that these pathways may be leveraged to complement more
      invasive procedures for diagnosis or assessment of disease severity, and that
      sarcoidosis and tuberculosis share overlap in gene regulation of specific
      inflammatory pathways.

PMID- 21852541
TI  - Attributable mortality of ventilator-associated pneumonia: a reappraisal using
      causal analysis.
AB  - RATIONALE: Measuring the attributable mortality of ventilator-associated
      pneumonia (VAP) is challenging and prone to different forms of bias. Studies
      addressing this issue have produced variable and controversial results.
      OBJECTIVES: We estimate the attributable mortality of VAP in a large multicenter
      cohort using statistical methods from the field of causal inference. METHODS:
      Patients (n = 4,479) from the longitudinal prospective (1997-2008) French
      multicenter Outcomerea database were included if they stayed in the intensive
      care unit (ICU) for at least 2 days and received mechanical ventilation (MV)
      within 48 hours after ICU admission. A competing risk survival analysis, treating
      ICU discharge as a competing risk for ICU mortality, was conducted using a
      marginal structural modeling approach to adjust for time-varying confounding by
      disease severity. MEASUREMENTS AND MAIN RESULTS: Six hundred eighty-five (15.3%)
      patients acquired at least one episode of VAP. We estimated that 4.4% (95%
      confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95%
      confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an
      observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds
      to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60.
      CONCLUSIONS: Our study on the attributable mortality of VAP is the first that
      simultaneously accounts for the time of acquiring VAP, informative loss to follow
      up after ICU discharge, and the existence of complex feedback relations between
      VAP and the evolution of disease severity. In contrast to the majority of
      previous reports, we detected a relatively limited attributable ICU mortality of
      VAP.

PMID- 21852542
TI  - Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo
      controlled study.
AB  - RATIONALE: Eosinophilic asthma is a phenotype of asthma characterized by the
      persistence of eosinophils in the airways. IL-5 is involved in the activation and
      survival of eosinophils. OBJECTIVES: To evaluate the effect of the antibody to IL
      5, reslizumab, in patients with eosinophilic asthma that is poorly controlled
      with high-dose inhaled corticosteroid. METHODS: Patients were randomly assigned
      to receive infusions of reslizumab at 3.0 mg/kg (n = 53) or placebo (n = 53) at
      baseline and at Weeks 4, 8, and 12, with stratification by baseline Asthma
      Control Questionnaire (ACQ) score less than or equal to 2 or greater than 2. The
      primary efficacy measure was the difference between the reslizumab and placebo
      groups in the change in ACQ score from baseline to end of therapy (Week 15 or
      early withdrawal). MEASUREMENTS AND MAIN RESULTS: Mean changes from baseline to
      end of therapy in ACQ score were -0.7 in the reslizumab group and -0.3 in the
      placebo group (P = 0.054) and in FEV(1) were 0.18 and -0.08 L, respectively (P =
      0.002). In those patients with nasal polyps, the changes in ACQ score were -1.0
      and -0.1, respectively (P = 0.012). Median percentage reductions from baseline in
      sputum eosinophils were 95.4 and 38.7%, respectively (P = 0.007). Eight percent
      of patients in the reslizumab group and 19% of patients in the placebo group had
      an asthma exacerbation (P = 0.083). The most common adverse events with
      reslizumab were nasopharyngitis, fatigue, and pharyngolaryngeal pain.
      CONCLUSIONS: Patients receiving reslizumab showed significantly greater
      reductions in sputum eosinophils, improvements in airway function, and a trend
      toward greater asthma control than those receiving placebo. Reslizumab was
      generally well tolerated.

PMID- 21852543
TI  - Burnout in ICU caregivers: a multicenter study of factors associated to centers.
AB  - RATIONALE: The stressful work environment of ICUs can lead to burnout. Burnout
      can impact on the welfare and performance of caregivers, and may lead them to
      resign their job. The shortage of ICU caregivers is becoming a real threat for
      health care leaders. OBJECTIVES: To investigate the factors associated with
      burnout on a national level in order to determine potential important factors.
      METHODS: Prospective, multicenter, observational survey of all caregivers from 74
      of the 92 Swiss ICUs, measuring the prevalence of burnout among the caregivers
      and the pre-specified center-, patient- and caregiver-related factors influencing
      its prevalence. MEASUREMENTS AND MAIN RESULTS: Out of the 4322 questionnaires
      distributed from March 2006 to April 2007, 3052 (71%) were returned, with a
      response rate of 72% by center, 69% from nurse-assistants, 73% from nurses and
      69% from physicians. A high proportion of female nurses among the team was
      associated with a decreased individual risk of high burnout (OR 0.98, 95% CI:0.97
      0.99 for every %). The caregiver-related factors associated with a high risk of
      burnout were being a nurse-assistant, being a male, having no children and being
      under 40 years old. CONCLUSIONS: The findings of this study seem to open a new
      frontier concerning burnout in ICUs, highlighting the importance of team
      composition. Our results should be confirmed in a prospective multicenter,
      multinational study. Whether our results can be exported to other medical
      settings where team-working is pivotal remains to be investigated.

PMID- 21852544
TI  - Comparative evaluation of MPT83 (Rv2873) for T helper-1 cell reactivity and
      identification of HLA-promiscuous peptides in Mycobacterium bovis BCG-vaccinated
      healthy subjects.
AB  - MPT83 (Rv2873), a surface lipoprotein excreted in the culture of Mycobacterium
      tuberculosis, is immunoreactive in antibody assays in humans and animals and
      provides protection as a combined DNA vaccine in mice and cattle. This study was
      undertaken to determine the reactivity of MPT83 in T helper 1 (Th1)-cell assays,
      i.e., antigen-induced proliferation and gamma interferon (IFN-gamma) secretion,
      using peripheral blood mononuclear cells (PBMCs) obtained from Mycobacterium
      bovis bacillus Calmette-Guerin (BCG)-vaccinated and/or M. tuberculosis-infected
      healthy subjects. PBMCs were tested with complex mycobacterial antigens and pools
      of synthetic peptides corresponding to MPT63, MPT83, MPB70, LppX, PPE68, CFP10,
      and ESAT-6. The results showed that MPT83 is among the strongest Th1 cell
      antigens of M. tuberculosis, and it was recognized equally strongly by BCG
      vaccinated and by BCG-vaccinated and M. tuberculosis-infected healthy subjects.
      Furthermore, HLA heterogeneity of the responding donors suggested that MPT83 was
      presented to Th1 cells by several HLA-DR molecules. The analysis of the mature
      MPT83 sequence (amino acids [aa] 1 to 220) and its 14 overlapping synthetic
      peptides for binding prediction to HLA class II molecules and actual recognition
      of the peptides by PBMCs from HLA-DR-typed subjects in antigen-induced
      proliferation and IFN-gamma assays suggested that Th1 cell epitopes were
      scattered throughout the sequence of MPT83. In addition, the HLA-promiscuous
      nature of at least three peptides, i.e., P11 (aa 151 to 175), P12 (aa 166 to
      190), and P14 (aa 196 to 220), was suggested by HLA-DR binding predictions and
      recognition by HLA-DR heterogeneous donors in Th1 cell assays. These results
      support the inclusion of MPT83 in an antigen cocktail to develop a new
      antituberculosis vaccine.

PMID- 21852545
TI  - Single and combination herpes simplex virus type 2 glycoprotein vaccines
      adjuvanted with CpG oligodeoxynucleotides or monophosphoryl lipid A exhibit
      differential immunity that is not correlated to protection in animal models.
AB  - Despite several attempts to develop an effective prophylactic vaccine for HSV-2,
      all have failed to show efficacy in the clinic. The most recent of these failures
      was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with
      the adjuvant monophosphoryl lipid A (MPL). In a phase 3 clinical trial, this
      vaccine failed to protect from HSV-2 disease, even though good neutralizing
      antibody responses were elicited. We aimed to develop a superior, novel HSV-2
      vaccine containing either gD or gB alone or in combination, together with the
      potent adjuvant CpG oligodeoxynucleotides (CPG). The immunogenic properties of
      these vaccines were compared in mice. We show that gB/CPG/alum elicited a
      neutralizing antibody response similar to that elicited by gD/CPG/alum vaccine
      but a significantly greater gamma interferon (IFN-gamma) T cell response.
      Furthermore, the combined gB-gD/CPG/alum vaccine elicited significantly greater
      neutralizing antibody and T cell responses than gD/MPL/alum. The efficacies of
      these candidate vaccines were compared in the mouse and guinea pig disease
      models, including a novel male guinea pig genital disease model. These studies
      demonstrated that increased immune response did not correlate to improved
      protection. First, despite a lower IFN-gamma T cell response, the gD/CPG/alum
      vaccine was more effective than gB/CPG/alum in mice. Furthermore, the gB
      gD/CPG/alum vaccine was no more effective than gD/MPL/alum in mice or male guinea
      pigs. We conclude that difficulties in correlating immune responses to efficacy
      in animal models will act as a deterrent to researchers attempting to develop
      effective HSV vaccines.

PMID- 21852546
TI  - Refinement of a human challenge model for evaluation of enterotoxigenic
      Escherichia coli vaccines.
AB  - Enterotoxigenic Escherichia coli (ETEC) strain H10407 (serotype O78:H11 producing
      heat-labile toxin [LT], heat-stable toxin [ST], and colonization factor I
      [CFA/I]) induces reliably high diarrheal attack rates (ARs) in a human challenge
      model at doses of >=10(9) CFU. A descending-dose challenge study was conducted
      with changes to the standard fasting time and buffer formulation, seeking
      conditions that permit lower inocula while maintaining reproducibly high ARs. In
      cohort 1, 20 subjects were fasted overnight and randomized 1:1:1:1 to receive
      H10407 at doses of 10(8) CFU with bicarbonate, 10(8) CFU with CeraVacx, 10(7) CFU
      with bicarbonate, or 10(7) CFU with CeraVacx. Subsequent cohorts received H10407
      (10(7) CFU with bicarbonate) with similar fasting conditions. Cohort 2 included
      15 ETEC-naive volunteers. Cohort 3 included 10 ETEC-naive volunteers and 10
      rechallenged volunteers. In all, 25/35 (71%) ETEC-naive recipients of 10(7) CFU
      of H10407 developed moderate or severe diarrhea (average maximum stool output/24
      h = 1,042 g), and most (97%) shed H10407 (maximum geometric mean titer = 7.5 *
      10(7) CFU/gram of stool). Only one of 10 rechallenged volunteers developed
      diarrhea. These rechallenged subjects had reduced intestinal colonization,
      reflected by quantitative microbiology of fecal samples. Among the 35 ETEC-naive
      subjects, anti-lipopolysaccharide (LPS) O78 serum antibody responses were
      striking, with positive IgA and IgG antibody responses in 33/35 (94%) and 25/35
      (71%), respectively. Anti-heat-labile enterotoxin (LTB) serum IgA and IgG
      responses developed in 19/35 (54%) and 14/35 (40%) subjects, respectively. Anti
      CFA/I serum IgA and IgG responses were detected in 15/35 (43%) and 8/35 (23%)
      subjects. After the second challenge, participants exhibited blunted anti-LPS and
      -LTB responses but a booster response to CFA/I. This ETEC model should prove
      useful in the future evaluation of ETEC vaccine candidates.

PMID- 21852547
TI  - Establishment of a new human pneumococcal standard reference serum, 007sp.
AB  - Lot 89SF has been the reference standard serum pool used in pneumococcal enzyme
      linked immunosorbent assays (ELISAs) since 1990. In 2005, it was estimated that
      there remained between 2 and 5 years' supply of lot 89SF. Since lot 89SF was the
      reference standard used in the evaluation of the seven-valent pneumococcal
      conjugate vaccine Prevnar (PCV7), the link to clinical efficacy would be severed
      if stocks became completely depleted. Furthermore, demonstration of immune
      responses comparable to those elicited by PCV7 is a licensure approach used for
      new pneumococcal conjugate vaccines, so a replacement reference standard was
      required. A total of 278 volunteers were immunized with the 23-valent
      unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was
      obtained twice within 120 days following immunization. Plasma was prepared,
      pooled, and confirmed to be free from hepatitis B virus (HBV), hepatitis C virus
      (HCV), and HIV. The pooled serum was poured at 6 ml per vial into 15,333 vials
      and lyophilized. Immunological bridging of 007sp to 89SF was used to establish
      equivalent reference values for 13 pneumococcal capsular serotypes (1, 3, 4, 5,
      6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) by five independent laboratories.
      Antibody concentrations in 007sp were established relative to the lot 89SF
      reference preparation using the WHO reference ELISA. Subsequently, 12 existing
      WHO calibration sera had concentrations reassigned for 13 pneumococcal serotypes
      using new serum 007sp as the reference, and these were compared to concentrations
      relative to the original reference serum. Agreement was excellent for the 12 WHO
      calibration sera. The 007sp preparation has replaced 89SF as the pneumococcal
      reference standard. Sufficient quantity of this new preparation is available such
      that, with judicious use, it should be available for at least 25 years.

PMID- 21852548
TI  - Evaluation of the recombinant 10-kilodalton immunodominant region of the BP26
      protein of Brucella abortus for specific diagnosis of bovine brucellosis.
AB  - Brucellosis is a disease with worldwide distribution affecting animals and human
      beings. Brucella abortus is the causative agent of bovine brucellosis. The cross
      reactions of currently available diagnostic procedures for B. abortus infection
      result in false-positive reactions, which make the procedures unreliable. These
      tests are also unable to differentiate Brucella-infected and -vaccinated animals.
      The present work is focused on the use of a nonlipopolysaccharide (LPS)
      diagnostic antigen, a recombinant 10-kDa (r10-kDa) protein of B. abortus, for
      specific diagnosis of brucellosis. The purified recombinant protein was used as a
      diagnostic antigen in plate enzyme-linked immunosorbent assay (p-ELISA) format to
      screen 408 bovine serum samples (70 presumptively negative, 308 random, and 30
      vaccinated), and the results were compared with those of the Rose Bengal plate
      agglutination test (RBPT) and the standard tube agglutination test (STAT).
      Statistical analysis in presumptive negative samples revealed 100 and 98.41%
      specificity of p-ELISA with RBPT and STAT, and an agreement of 91.43% with the
      tests using Cohen's kappa statistics. In random samples, the agreement of p-ELISA
      was 77.92% and 80.52% with RBPT and STAT, respectively. p-ELISA investigation of
      vaccinated samples reported no false-positive results, whereas RBPT and STAT
      reported 30% and 96.6% false-positive results, respectively. The data suggest
      that p-ELISA with r10-kDa protein may be a useful method for diagnosis of bovine
      brucellosis. Furthermore, p-ELISA may also be used as a tool for differentiating
      Brucella-vaccinated and naturally infected animals.

PMID- 21852550
TI  - MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and
      vascular remodeling in vivo.
AB  - RATIONALE: MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac
      muscle biology and pathophysiology. However, their expression and regulation in
      vascular cell physiology and disease is currently unknown. OBJECTIVE: The aim of
      the present study was to evaluate the role, if any, of miR-1 and miR-133 in
      vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo.
      METHODS AND RESULTS: We demonstrate here that miR-133 is robustly expressed in
      vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular
      levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic
      switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per
      se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2
      activation and is inversely correlated with VSMC growth. Indeed, miR-133
      decreases when VSMCs are primed to proliferate in vitro and following vascular
      injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in
      vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR
      133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces
      but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in
      vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in
      vitro and in vivo and through Sp-1 repression regulates smooth muscle gene
      expression. CONCLUSIONS: Our data show that miR-133 is a key regulator of
      vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting
      its potential therapeutic application for vascular diseases.

PMID- 21852549
TI  - Vaccination of dams increases antibody titer and improves growth parameters in
      finisher pigs subclinically infected with porcine circovirus type 2.
AB  - Porcine circovirus type 2 (PCV2) is the obligate infectious agent in postweaning
      multisystemic wasting syndrome (PMWS) of pigs. To control PMWS, we vaccinated
      dams at 4 and 2 weeks before pregnancy and again in the 12th week of gestation
      with an inactivated PCV2 vaccine (Circovac). Two producer farms run under the
      control of Swiss Swine Health Organization were selected for the experiment.
      Previously, in one farm PMWS was diagnosed on pigs after weaning, whereas in the
      other farm, pigs wasted during the fattening period. For the experiments 113 dams
      were randomly vaccinated, and 111 dams were sham injected. Vaccination increased
      serum antibodies in dams 3- to 9-fold, accompanied by serum antibody titer
      increases in their offspring. In the sixth week of life, progeny from vaccinated
      dams had about the same IgG antibody titers as progeny of unvaccinated dams at
      the third day of life. In sera of vaccinated dams only low concentrations of PCV2
      DNA were detected, and no progeny developed PMWS. Interestingly, at day 56 four
      progeny of unvaccinated dams tested positive for anti-PCV2 IgM antibodies,
      indicating a primary infection with PCV2. Of economic importance is the
      observation that progeny of vaccinated dams had a significantly higher daily
      weight gain in the fattening period (farm X, +51 g/day; farm Y, +30 g/day) and
      thus a shortened fattening period of about 6 days compared to progeny of
      controls. To our knowledge this is the first demonstration of subclinical
      circovirus infection and its effects on growth performance of fattening pigs by
      vaccination of dams.

PMID- 21852551
TI  - Distribution and functional role of inositol 1,4,5-trisphosphate receptors in
      mouse sinoatrial node.
AB  - RATIONALE: Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) have been implicated
      in the generation of arrhythmias and cardiac muscle nuclear signaling. However,
      in the mammalian sinoatrial node (SAN), where the heart beat originates, the
      expression and functional activity of IP(3)Rs have not been investigated.
      OBJECTIVES: To determine whether SAN express IP(3)Rs and which isoforms are
      present. To examine the response of the SAN to IP(3)R agonists and antagonist,
      and the potential role played by IP(3)Rs in cardiac pacemaking. METHODS AND
      RESULTS: The expression and distribution of IP(3)Rs were studied by reverse
      transcription polymerase chain reaction, Western blotting, and immunolabeling.
      Ca(2+) signaling and electric activity in intact mouse SAN were measured with
      Ca(2+)-sensitive fluorescent dyes. We found that although the entire SAN
      expressed three IP(3)R mRNA isoforms, the type II IP(3)R (IP(3)R2) was the
      predominant protein isoform detected by Western blot using protein extracts from
      the SAN, atrioventricular node, and atrial tissue. Immunohistochemistry studies
      also showed that IP(3)R2 was expressed in the central SAN region. Studies using
      isolated single pacemaker cells revealed that IP(3)R2 (but not IP(3)R1) was
      located with a similar distribution to the sarcoplasmic reticulum marker protein
      SERCA2a with some labeling adjacent to the surface membrane. The application of
      membrane-permeable IP(3) (IP(3)-butyryloxymethyl ester) increased Ca(2+) spark
      frequency and the pacemaker firing rate in single isolated pacemaker cells. In
      intact SAN preparations, IP(3)R agonists, endothelin-1 and IP(3)-butyryloxymethyl
      ester both increased intracellular Ca(2+) and the pacemaker firing rate, whereas
      the IP(3)R antagonist, 2-aminoethoxydiphenyl borate decreased Ca(2+) and the
      firing rate. Both of these effects were absent in the SAN from transgenic IP(3)R2
      knockout mice. CONCLUSIONS: This study provides new evidence that functional
      IP(3)R2s are expressed in the mouse SAN and could serve as an additional Ca(2+)
      dependent mechanism in modulating cardiac pacemaker activity as well as other
      Ca(2+)-dependent processes.

PMID- 21852552
TI  - Paracrine proliferative signaling by senescent cells in world health organization
      group 3 pulmonary hypertension: age corrupting youth?

PMID- 21852553
TI  - Patching up the myocardium.

PMID- 21852554
TI  - Robert Jennings: a labor of love in the laboratory. Interview by Ruth Williams.

PMID- 21852557
TI  - Microparticles, vascular function, and atherothrombosis.
AB  - Membrane-shed submicron microparticles (MPs) are released after cell activation
      or apoptosis. High levels of MPs circulate in the blood of patients with
      atherothrombotic diseases, where they could serve as a useful biomarker of
      vascular injury and a potential predictor of cardiovascular mortality and major
      adverse cardiovascular events. Atherosclerotic lesions also accumulate large
      numbers of MPs of leukocyte, smooth muscle cell, endothelial, and erythrocyte
      origin. A large body of evidence supports the role of MPs at different steps of
      atherosclerosis development, progression, and complications. Circulating MPs
      impair the atheroprotective function of the vascular endothelium, at least
      partly, by decreased nitric oxide synthesis. Plaque MPs favor local inflammation
      by augmenting the expression of adhesion molecule, such as intercellular adhesion
      molecule -1 at the surface of endothelial cell, and monocyte recruitment within
      the lesion. In addition, plaque MPs stimulate angiogenesis, a key event in the
      transition from stable to unstable lesions. MPs also may promote local cell
      apoptosis, leading to the release and accumulation of new MPs, and thus creating
      a vicious circle. Furthermore, highly thrombogenic plaque MPs could increase
      thrombus formation at the time of rupture, together with circulating MPs released
      in this context by activated platelets and leukocytes. Finally, MPs also could
      participate in repairing the consequences of arterial occlusion and tissue
      ischemia by promoting postischemic neovascularization.

PMID- 21852555
TI  - The regulation of valvular and vascular sclerosis by osteogenic morphogens.
AB  - Vascular calcification increasingly afflicts our aging, dysmetabolic population.
      Once considered only a passive process of dead and dying cells, vascular
      calcification has now emerged as a highly regulated form of biomineralization
      organized by collagenous and elastin extracellular matrices. During skeletal bone
      formation, paracrine epithelial-mesenchymal and endothelial-mesenchymal
      interactions control osteochondrocytic differentiation of multipotent mesenchymal
      progenitor cells. These paracrine osteogenic signals, mediated by potent
      morphogens of the bone morphogenetic protein and wingless-type MMTV integration
      site family member (Wnt) superfamilies, are also active in the programming of
      arterial osteoprogenitor cells during vascular and valve calcification.
      Inflammatory cytokines, reactive oxygen species, and oxylipids-increased in the
      clinical settings of atherosclerosis, diabetes, and uremia that promote
      arteriosclerotic calcification-elicit the ectopic vascular activation of
      osteogenic morphogens. Specific extracellular and intracellular inhibitors of
      bone morphogenetic protein-Wnt signaling have been identified as contributing to
      the regulation of osteogenic mineralization during development and disease. These
      inhibitory pathways and their regulators afford the development of novel
      therapeutic strategies to prevent and treat valve and vascular sclerosis.

PMID- 21852558
TI  - Directed differentiation of skin-derived precursors into functional vascular
      smooth muscle cells.
AB  - OBJECTIVE: The goal of this study was to characterize the factors and conditions
      required for smooth muscle cell (SMC)-directed differentiation of Sox2(+)
      multipotent rat and human skin-derived precursors (SKPs) and to define whether
      they represent a source of fully functional vascular SMCs for applications in
      vivo. METHODS AND RESULTS: We found that rat SKPs can differentiate almost
      exclusively into SMCs by reducing serum concentrations to 0.5% to 2% and plating
      them at low density. Human SKPs derived from foreskin required the addition of
      transforming growth factor-beta1 or -beta3 to differentiate into SMCs, but they
      did so even in the absence of serum. SMC formation was confirmed by quantitative
      reverse transcription-polymerase chain reaction, immunocytochemistry, and
      fluorescence-activated cell sorting, with increased expression of smoothelin-B
      and little to no expression of telokin or smooth muscle gamma-actin, together
      indicating that SKPs differentiated into vascular rather than visceral SMCs. Rat
      and human SKP-derived SMCs were able to contract in vitro and also wrap around
      and support new capillary and larger blood vessel formation in angiogenesis
      assays in vivo. CONCLUSIONS: SKPs are Sox2(+) progenitors that represent an
      attainable autologous source of stem cells that can be easily differentiated into
      functional vascular SMCs in defined serum-free conditions without reprogramming.
      SKPs represent a clinically viable cell source for potential therapeutic
      applications in neovascularization.

PMID- 21852559
TI  - Inhibition of in-stent stenosis by oral administration of bindarit in porcine
      coronary arteries.
AB  - OBJECTIVE: We have previously demonstrated that bindarit, a selective inhibitor
      of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal
      formation in rodent models of vascular injury by reducing smooth muscle cell
      proliferation and migration and neointimal macrophage content, effects associated
      with the inhibition of MCP-1/CCL2 production. The aim of the current study was to
      evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine
      coronary stent model. METHODS AND RESULTS: One or 2 bare metal stents (Multi-Link
      Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of
      42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was
      administered orally from 2 days before stenting until the time of euthanasia at 7
      and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%,
      P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%,
      P<0.001), and inflammatory score (40%, P<0.001) compared with control animals,
      whereas there was no significant difference in the injury score between the 2
      groups. Moreover, treatment with bindarit significantly reduced the number of
      proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content
      (by 55%, P<0.01; n=5-6 group) in stented arteries at day 7 and 28, respectively.
      These effects were associated with a significant (P<0.05) reduction of MCP-1
      plasma levels at day 28. In vitro data showed that bindarit (10-300 MUmol/L)
      reduced tumor necrosis factor-alpha (50 ng/mL)-induced pig coronary artery smooth
      muscle cell proliferation and inhibited MCP-1 production. CONCLUSION: Our results
      show the efficacy of bindarit in the prevention of porcine in-stent stenosis and
      support further investigation for clinical application of this compound.

PMID- 21852556
TI  - Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel.
AB  - Artery calcification reflects an admixture of factors such as ectopic
      osteochondral differentiation with primary host pathological conditions. We
      review how genetic factors, as identified by human genome-wide association
      studies, and incomplete correlations with various mouse studies, including
      knockout and strain analyses, fit into "pieces of the puzzle" in intimal
      calcification in human atherosclerosis, and artery tunica media calcification in
      aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp
      contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial
      calcification. Specifically, each is a minor component in the function of a much
      larger network of factors that exert balanced effects to promote and suppress
      arterial calcification. For the network to normally suppress spontaneous arterial
      calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working
      order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular
      pathophysiology of closely related but phenotypically different diseases
      (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum
      (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which
      premature onset arterial calcification is a prominent but not the sole feature.

PMID- 21852560
TI  - Focal adhesion kinase-related nonkinase inhibits vascular smooth muscle cell
      invasion by focal adhesion targeting, tyrosine 168 phosphorylation, and
      competition for p130(Cas) binding.
AB  - OBJECTIVE: Focal adhesion kinase-related nonkinase (FRNK), the C-terminal domain
      of focal adhesion kinase (FAK), is a tyrosine-phosphorylated, vascular smooth
      muscle cell (VSMC)-specific inhibitor of cell migration. FRNK inhibits both FAK
      and proline-rich tyrosine kinase 2 (PYK2) in cultured VSMCs, and both kinases may
      be involved in VSMC invasion during vascular remodeling. METHODS AND RESULTS:
      Adenovirally mediated gene transfer of green fluorescent protein-tagged, wild
      type (wt) FRNK into balloon-injured rat carotid arteries confirmed that FRNK
      overexpression inhibited both FAK and PYK2 phosphorylation and downstream
      signaling in vivo. To identify which kinase was involved in regulating VSMC
      invasion, adenovirally mediated expression of specific short hairpin RNAs was
      used to knock down FAK versus PYK2 in cultured VSMCs, but only FAK short hairpin
      RNA was effective in reducing VSMC invasion. The role of FRNK tyrosine
      phosphorylation was then examined using adenoviruses expressing
      nonphosphorylatable (Tyr168Phe-, Tyr232Phe-, and Tyr168,232Phe-) green
      fluorescent protein-FRNK mutants. wtFRNK and all FRNK mutants localized to FAs,
      but only Tyr168 phosphorylation was required for FRNK to inhibit invasion.
      Preventing Tyr168 phosphorylation also increased FRNK-paxillin interaction, as
      determined by coimmunoprecipitation, total internal reflection fluorescence
      microscopy, and fluorescence recovery after photobleaching. Furthermore, wtFRNK
      competed with FAK for binding to p130(Cas) (a critically important regulator of
      cell migration) and prevented its phosphorylation. However, Tyr168Phe-FRNK was
      unable to bind p130(Cas). CONCLUSION: We propose a 3-stage mechanism for FRNK
      inhibition: focal adhesion targeting, Tyr168 phosphorylation, and competition
      with FAK for p130 binding and phosphorylation, which are all required for FRNK to
      inhibit VSMC invasion.

PMID- 21852561
TI  - CCL20 is increased in hypercholesterolemic subjects and is upregulated by LDL in
      vascular smooth muscle cells: role of NF-kappaB.
AB  - OBJECTIVE: Our aim was to analyze the regulation of CC Chemokine ligand 20
      (CCL20) by LDL in human vascular smooth muscle cells (VSMC). METHODS AND RESULTS:
      In asymptomatic subjects, circulating CCL20 levels were higher in patients with
      hypercholesterolemia (18.5+/-3.2 versus 9.1+/-1.3 pg/mL; P<0.01). LDL induced the
      expression of CCL20 in VSMC in a dose- and time-dependent manner. Increased
      levels of CCL20 secreted by LDL-treated VSMC significantly induced human
      lymphocyte migration, an effect reduced by CCL20 silencing. The upregulation of
      CCL20 by LDL was dependent on the activation of kinase signaling pathways and NF
      kappaB. By site-directed mutagenesis, electrophoretic mobility shift assay, and
      chromatin immunoprecipitation, we identified a NF-kappaB site (-80/-71) in CCL20
      promoter critical for LDL responsiveness. Lysophosphatidic acid mimicked the
      upregulation of CCL20 induced by LDL, and minimal oxidation of LDL increased the
      ability of LDL to induce CCL20 through a mechanism that involves lysophosphatidic
      acid receptors. CCL20 was overexpressed in atherosclerotic lesions from coronary
      artery patients, colocalizing with VSMC. CCL20 was detected in conditioned media
      from healthy human aorta and its levels were significantly higher in secretomes
      from carotid endarterectomy specimens. CONCLUSION: This study identifies CCL20 in
      atherosclerotic lesions and recognizes this chemokine as a mediator highly
      sensitive to the inflammatory response elicited by LDL.

PMID- 21852562
TI  - Left atrial blood stasis and Von Willebrand factor-ADAMTS13 homeostasis in atrial
      fibrillation.
AB  - OBJECTIVE: Left atrial blood stasis is associated with increased risk for left
      atrial appendage thrombus (LAAT) and stroke in atrial fibrillation (AF). Von
      Willebrand factor (VWF) is associated with thromboembolism in AF. VWF
      thrombogenic activity is proportional to multimer size, which is regulated by VWF
      cleaving protease (ADAMTS13). METHODS AND RESULTS: To assess the association
      between left atrial blood stasis and VWF-ADAMTS13 system, plasma VWF antigen
      (VWF:Ag), VWF activity (VWF:Act), and ADAMTS13 activity were measured in 414
      consecutive patients with nonvalvular AF (age 63+/-13 years; 25% women) and in
      100 patients (age 64+/-14 years; 39% women) with normal sinus rhythm. Spontaneous
      echocardiographic contrast (SEC), left atrial appendage emptying velocity, and
      LAAT were assessed by transesophageal echocardiography. Presence and intensity of
      SEC varied directly with VWF:Ag and VWF:Act but not with ADAMTS13 activity. AF
      patients with LAAT had higher VWF:Ag (200+/-61 versus 155+/-52, P=0.0006) and
      VWF:Act (179+/-57 versus 141+/-51 P=0.0026) compared with those without LAAT.
      VWF:Ag and VWF:Act were independent predictors of LAAT after adjustment for
      CHADS2 score (P=0.0179 and P=0.0497, respectively). CONCLUSION: The association
      between VWF and SEC may explain the thrombotic propensity in AF. Elevated VWF:Ag
      may help identify AF patients at risk for LAAT.

PMID- 21852563
TI  - AMPK alpha 1-induced RhoA phosphorylation mediates vasoprotective effect of
      estradiol.
AB  - OBJECTIVE: Estradiol (E2) mediates numerous beneficial effects assigned to
      estrogens, but whereas mechanisms have been described at the endothelial level,
      direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As
      evidence accumulates regarding the role of RhoA in vascular pathophysiology and
      the benefit of RhoA-Rho associated protein kinase (Rock) pathway inhibition, we
      analyzed if E2 could inhibit it in VSMC. METHODS AND RESULTS: We show that in
      VSMC, E2 inhibits the RhoA-Rock pathway in a time- and concentration-dependent
      manner. The inhibition of RhoA-Rock pathway results from E2-induced
      phosphorylation of the Ser188 of RhoA. Using pharmacological, transfection, and
      in vitro phosphorylation experiments, we demonstrate that AMP-activated protein
      kinase subunit alpha 1 (AMPKalpha1) is activated by estrogen receptor stimulation
      and catalyzes RhoA phosphorylation induced by E2. Ex vivo, ovariectomy leads to
      an increase in the amplitude of phenylephrine- or serotonine-induced contractions
      of aortic rings in wild-type mice but not in AMPKalpha1-knock-out mice or E2
      supplemented animals. These functional effects were correlated with a reduced
      level of RhoA phosphorylation in the aorta of ovariectomized female, male, and
      AMPKalpha1 knock-out mice. CONCLUSION: Our work thus defines AMPKalpha1 as (1) a
      new kinase for RhoA and (2) a new mediator of the vasoprotective effects of
      estrogen.

PMID- 21852565
TI  - Cancellation of MR imaging-guided breast biopsy due to lesion nonvisualization:
      frequency and follow-up.
AB  - PURPOSE: To determine the rate of canceled magnetic resonance (MR) imaging-guided
      breast biopsies due to nonvisualization of the lesion and to assess associated
      features and outcome data for these cases. MATERIALS AND METHODS: With the
      approval of the institutional review board, a HIPAA-compliant retrospective
      review, in which the requirement for informed consent was waived, was performed
      for 907 patients scheduled for MR imaging-guided breast biopsy from 2004 to 2008.
      In 70 patients, MR imaging biopsy was canceled due to lesion nonvisualization.
      Medical records and imaging studies were reviewed to identify patient,
      parenchymal, lesion features and outcome data. Statistical analysis was performed
      with the Fisher exact test. The 95% confidence interval (CI) was calculated.
      RESULTS: Cancellation of MR-guided biopsy due to lesion nonvisualization occurred
      in 8% (70 of 907) of patients and in 8% (74 of 911) of lesions. Factors
      associated with a significantly higher cancellation rate included marked and
      moderate versus mild and minimal background parenchymal enhancement (38 of 316
      [12%] vs 32 of 591 [5%], P = .001), extremely and heterogeneously dense versus
      scattered fibroglandular densities and fatty parenchymal volume (64 of 712 [9%]
      vs six of 195 [3%], P = .006), and lesions 1 cm or less in size (52 of 520 [10%]
      vs 22 of 391 [6%], P = .02).The rate of cancellation per year was highest in the
      first year, with a decrease in subsequent years (14 of 102 [14%] vs 56 of 805
      [7%], P = .025). A significantly lower rate was found in women with synchronous
      breast cancer (nine of 240 [4%] vs 61 of 667 [9%], P = .007), and a significantly
      higher rate was found in women with a history of cancer (35 of 315 [11%] vs 35 of
      592 [6%], P = .01). Among 58 women who had MR imaging follow-up, no cancers were
      identified. Among three women who underwent mastectomy after cancellation, one
      had ductal carcinoma in situ in the same quadrant as the MR-depicted lesion. The
      cancer detection rate among 61 women who underwent either MR imaging or
      pathologic follow-up was 2% (one of 61) (95% CI: 0.4%, 9%). CONCLUSION: MR
      imaging-guided breast biopsy was canceled due to lesion nonvisualization in 8% of
      the patients. Although the cancer detection rate among the lesions for which
      biopsy was canceled is low (95% CI: 0%, 9%), short-term follow-up MR imaging is
      prudent.

PMID- 21852564
TI  - Nitric oxide decreases the expression of endothelin-converting enzyme-1 through
      mRNA destabilization.
AB  - OBJECTIVE: Endothelial function depends on the equilibrium in the synthesis of
      vasoactive endothelial factors. It is well known that endothelin and nitric oxide
      (NO) exhibit reciprocal regulation. We assessed the ability of NO to regulate
      endothelin-converting enzyme-1 (ECE-1) expression in vascular endothelial cells.
      METHODS AND RESULTS: Bovine aortic endothelial cells were incubated with 2
      different NO donors as well as with a cyclic-GMP analog, dibutyryl-cGMP (dB
      cGMP). ECE-1 protein content and mRNA expression were evaluated by Western blot
      and Northern blot, respectively, promoter activity by transfection experiments,
      ECE-1 activity by ELISA, and cGMP production by radioimmunoassay. Both NO donors
      decreased ECE-1 protein content, mRNA expression, and ECE-1 activity. ODQ, an
      inhibitor of soluble guanylyl cyclase, blocked those effects. NO donors raised
      cGMP levels, and dB-cGMP mimicked their effects on ECE-1 expression, which were
      blocked by KT5823, a nonspecific PKG inhibitor. The changes on ECE-1 expression
      were due to a destabilization on 3'-untranslated region (3'-UTR) of this mRNA,
      because the activity of a luciferase reporter construct containing the 3'-UTR of
      the ECE-1 gene was reduced by dB-cGMP in a PKG-dependent manner. The biological
      relevance of this regulation was confirmed in bovine aortic endothelial cells
      coincubated with macrophages in the presence of lipopolysaccharide, in eNOS
      deficient mice, and in Wistar rats treated with NO donors. In every case, an
      inverse relationship was observed between NO and ECE-1 protein content.
      CONCLUSION: Our results support that NO regulates ECE-1 expression through a
      cGMP/PKG-dependent regulatory mechanism at the post-transcriptional level via the
      3'-UTR of the ECE-1 gene.

PMID- 21852566
TI  - Computed diffusion-weighted MR imaging may improve tumor detection.
AB  - PURPOSE: To describe computed diffusion weighted (DW) magnetic resonance (MR)
      imaging as a method for obtaining high-b-value images from DW MR imaging
      performed at lower b values and to investigate the feasibility of the technique
      to improve lesion detection in oncologic cases. MATERIALS AND METHODS: The study
      was approved by the institutional and research committee, and written informed
      consent was obtained from all patients. DW MR imaging was performed on a CuSO(4)
      phantom at 1.5 T with a range of b values and compared with computed DW MR
      imaging images synthesized from lower b values (0 and 600 sec/mm(2)). The signal
      to-noise ratio (SNR) was compared, and agreement between the SNR of computed DW
      MR imaging and theoretical estimation assessed. Computed DW MR imaging was
      evaluated in 10 oncologic patients who underwent whole-body DW MR imaging with b
      values of 0 and 900 sec/mm(2). Computed DW MR images at computed b values of 1500
      and 2000 sec/mm(2) were generated. The image quality and background suppression
      of acquired and computed images were rated by a radiologist using a four-point
      scale. The diagnostic performance for malignant lesion detection using these
      images was evaluated and compared by using the McNemar Test. RESULTS: The SNR of
      computed DW MR imaging of the phantom conformed closely to theoretical
      predictions. Computed DW MR imaging resulted in a higher SNR compared with
      acquired DW MR imaging, especially at b values greater than 840 sec/mm(2). In
      patients, images with a computed b value of 2000 sec/mm(2) produced good image
      quality and high background suppression (mean scores of 2.8 and 4.0,
      respectively). Evaluation of images with a computed b value of 2000 sec/mm(2)
      resulted in higher overall diagnostic sensitivity (96.0%) and specificity (96.6%)
      compared with images with an acquired b value of 900 sec/mm(2) (sensitivity,
      89.4%; specificity, 87.5%; P < .01). CONCLUSION: Computed DW MR imaging in the
      body allows higher-b-value images to be obtained with a good SNR. Clinical
      computed DW MR imaging is feasible and may improve disease detection.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101919/-/DC1.

PMID- 21852567
TI  - Abdominal dynamic CT in patients with renal dysfunction: contrast agent dose
      reduction with low tube voltage and high tube current-time product settings at
      256-detector row CT.
AB  - PURPOSE: To evaluate the feasibility of a low-contrast agent dose protocol at
      abdominal dynamic computed tomography (CT) with a low tube voltage high tube
      current-time product technique and a 256-detector row CT unit. MATERIALS AND
      METHODS: This prospective study received institutional review board approval;
      written informed consent to participate was obtained from all patients. The study
      included 151 patients; 117 had an estimated glomerular filtration rate (eGFR)
      greater than or equal to 60 mL/min/1.73 m(2). These patients were examined with
      the conventional 120-kVp protocol. The other 34 patients underwent scanning with
      an 80-kVp tube voltage, a high tube current-time product, and a 40% reduction in
      contrast agent dose. Effective dose (ED), image noise, attenuation, contrast-to
      noise ratio (CNR), and figure of merit of the aorta in the arterial phase and of
      the portal vein and hepatic parenchyma in the portal venous phase in the two
      groups were compared with the Student t test. RESULTS: Estimated ED was about 20%
      lower with the 80-kVp protocol than with the 120-kVp protocol. There were no
      significant differences in CNR in any region of interest between the 80-kVp
      protocol and the 120-kVp protocol (abdominal aorta: 36.9 +/- 9.7 [standard
      deviation] vs 36.1 +/- 8.1, P = .63; portal vein: 13.4 +/- 3.2 vs 13.1 +/- 3.2, P
      = .65; hepatic parenchyma: 6.4 +/- 2.6 vs 6.7 +/- 2.3, P = .51). CONCLUSION:
      Contrast dose at hepatic dynamic 256-detector row CT in patients with renal
      dysfunction can be decreased by 40% with this protocol by using the 80-kVp
      setting and a high tube current-time product.

PMID- 21852568
TI  - Assessment of white matter microstructural integrity in children with syndromic
      craniosynostosis: a diffusion-tensor imaging study.
AB  - PURPOSE: To assess whether architectural alterations exist in the white matter of
      patients with syndromic and complex craniosynostosis. MATERIALS AND METHODS: The
      medical ethics committee approved this study. Written informed consent was
      obtained from parents or guardians before imaging. A prospective study was
      performed in children with syndromic and complex craniosynostosis aged 6-14
      years. Forty-five patients were included: four had Apert syndrome, 14 had Crouzon
      Pfeiffer syndrome, eight had Muenke syndrome, 11 had Saethre-Chotzen syndrome,
      and eight had complex craniosynostosis. In addition, seven control subjects were
      evaluated. For diffusion-tensor imaging, an echo-planar sequence was used with a
      diffusion gradient (b = 1000 sec/mm(2)) applied in 25 noncollinear directions.
      Regions of interest (ROIs) were placed in the following white matter structures:
      pontine crossing tract, corticospinal tracts, medial cerebral peduncles, uncinate
      fasciculus (measured bilaterally), anterior commissure, frontal and occipital
      white matter (measured bilaterally), fornix, corpus callosum (measured in the
      genu and splenium), and corpus cingulum (measured bilaterally). Eigenvalues were
      measured in all ROIs and fractional anisotropy (FA) was calculated. RESULTS:
      Across all measured ROIs, FA values were generally lower in all patients combined
      than in the control subjects (P < .001). There were no significant differences
      among subgroups of patients. CONCLUSION: Diffusion-tensor imaging measurements of
      white matter tracts reveal significant white matter integrity differences between
      children with craniosynostosis and healthy control subjects. This could imply
      that the developmental delays seen in these patients could be caused by the
      presence of a primary disorder of the white matter microarchitecture.

PMID- 21852569
TI  - Non-small cell lung cancer: detection of early response to chemotherapy by using
      contrast-enhanced dynamic and diffusion-weighted MR imaging.
AB  - PURPOSE: To evaluate the ability of dynamic contrast material-enhanced and
      diffusion-weighted (DW) magnetic resonance (MR) imaging to help detect early
      response to chemotherapy in patients with non-small cell lung cancer (NSCLC).
      MATERIALS AND METHODS: This study was approved by the institutional review board,
      and written informed consent was obtained from all subjects. Twenty-eight
      patients with stage IIIB or IV NSCLC (17 women, 11 men; mean age, 64.8 years) who
      underwent chemotherapy were enrolled. All patients underwent MR imaging before
      and after the first course of chemotherapy. The time to peak enhancement, maximum
      enhancement ratio, and washout ratio were determined from the time-signal
      intensity curves of dynamic contrast-enhanced MR images. The apparent diffusion
      coefficient (ADC) of each lung carcinoma was calculated from DW MR images. The
      responses of these parameters to the first course of chemotherapy and the
      pretreatment ADC itself were compared with final tumor size reduction by using
      the Pearson correlation coefficient. Kaplan-Meier curves of progression-free
      survival and overall survival were generated, and comparisons between the group
      with a good response of the significant parameter (upper 50th percentile) and
      that with a poor response of the significant parameter (lower 50th percentile)
      were performed by using a two-sided log-rank test. RESULTS: Significant
      correlation was found only between early ADC change and final tumor size
      reduction rate (r(2) = 0.41, P = .00025). The median progression-free survival
      for the group with a good increase in ADC was 12.1 months, and that for the group
      with a stable or decreased ADC was 6.67 months (P = .021), while median overall
      survival was 22.4 and 12.3 months, respectively (P = .048). CONCLUSION: ADC seems
      to be a promising tool for monitoring the early response to or predicting
      prognosis after chemotherapy of NSCLC.

PMID- 21852570
TI  - Tumoral and nontumoral pancreas: correlation between quantitative dynamic
      contrast-enhanced MR imaging and histopathologic parameters.
AB  - PURPOSE: To prospectively determine whether dynamic contrast material-enhanced
      (DCE) magnetic resonance (MR) quantitative parameters correlate with fibrosis and
      microvascular density (MVD) in malignant and benign solid pancreatic focal
      lesions and nontumoral pancreatic tissue. MATERIALS AND METHODS: The
      institutional review board approved the study; written informed consent was
      obtained. DCE MR was performed in 28 patients with surgically resectable focal
      pancreatic lesions. DCE MR quantitative parameters derived from one-compartment
      (OC) (transfer rate constant [K(trans)] and distribution fraction [f]) and two
      compartment (TC) (K(trans), tissue volume fraction occupied by extravascular
      extracellular space [v(i)], and tissue volume fraction occupied by vascular space
      [v(p)]) pharmacokinetic models were correlated with fibrosis content and MVD
      counts in focal lesions and nontumoral tissue (Spearman correlation coefficient
      [SCC]). Pharmacokinetic parameters were compared (Mann-Whitney test) between
      tumoral and nontumoral tissue. Diagnostic performance of DCE MR fibrosis
      detection was assessed (receiver operator characteristic curve analysis).
      RESULTS: K(trans) OC and K(trans) TC were significantly lower in primary
      malignant tumors compared with benign lesions (P = .023) and nontumoral
      pancreatic tissue downstream (P < .001) and upstream (P = .006); f and v(i) were
      significantly higher in primary malignant tumors compared with nontumoral
      pancreatic tissue downstream (P = .012 and .018, respectively). Fibrosis was
      correlated negatively with K(trans) OC (SCC, -0.600) and K(trans) TC (SCC, 
      0.564) and positively with f (SCC, 0.514) and v(i) (SCC, 0.464), with P < .001
      (all comparisons). MVD was positively correlated with f (SCC, 0.355; P = .019)
      and v(i) (SCC, 0.297; P = .038) but not with K(trans) OC (SCC, -0.140; P = .33)
      and K(trans) TC (SCC, -0.194; P = .181). Sensitivity and specificity for fibrosis
      detection were 65% (24 of 37) and 83% (10 of 12) for K(trans) OC (cutoff value,
      0.35 min(-1)) and 76% (28 of 37) and 83% (10 of 12) for K(trans) TC (cutoff
      value, 0.29 min(-1)), respectively. CONCLUSION: Quantitative DCE MR parameters,
      derived from pharmacokinetic models in malignant and benign pancreatic solid
      lesions and nontumoral pancreatic tissue, were significantly correlated with
      fibrosis and MVD. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11103515/-/DC1.

PMID- 21852572
TI  - Energetics of Al13 Keggin cluster compounds.
AB  - The epsilon-Al(13) Keggin aluminum hydroxide clusters are essential models in
      establishing molecular pathways for geochemical reactions. Enthalpies of
      formation are reported for two salts of aluminum centered epsilon-Keggin
      clusters, Al(13) selenate, (Na(AlO(4))Al(12)(OH)(24)(SeO(4))(4)*12H(2)O) and
      Al(13) sulfate, (NaAlO(4)Al(12)(OH)(24)(SO(4))(4)*12H(2)O). The measured
      enthalpies of solution, DeltaH(sol), at 28  degrees C in 5 N HCl for the epsilon
      Al(13) selenate and sulfate are -924.57 (+/- 3.83) and -944.30 ( +/- 5.66)
      kJ.mol(-1), respectively. The enthalpies of formation from the elements,
      DeltaH(f,el), for Al(13) selenate and sulfate are -19,656.35 ( +/- 67.30) kJ.mol(
      1), and -20,892.39 ( +/- 70.01) kJ.mol(-1), respectively. In addition,
      DeltaH(f,el) for sodium selenate decahydrate was calculated using data from high
      temperature oxide melt solution calorimetry measurements: -4,006.39 ( +/- 11.91)
      kJ.mol(-1). The formation of both epsilon-Al(13) Keggin cluster compounds is
      exothermic from oxide-based components but energetically unfavorable with respect
      to a gibbsite-based assemblage. To understand the relative affinity of the
      epsilon-Keggin clusters for selenate and sulfate, the enthalpy associated with
      two S-Se exchange reactions was calculated. In the solid state, selenium is
      favored in the Al(13) compound relative to the binary chalcogenate, while in 5 N
      HCl, sulfur is energetically favored in the cluster compound compared to the
      aqueous solution. This contribution represents the first thermodynamic study of
      epsilon-Al(13) cluster compounds and establishes a method for other such
      molecules, including the substituted versions that have been created for kinetic
      studies. Underscoring the importance of epsilon-Al(13) clusters in natural and
      anthropogenic systems, these data provide conclusive thermodynamic evidence that
      the Al(13) Keggin cluster is a crucial intermediate species in the formation
      pathway from aqueous aluminum monomers to aluminum hydroxide precipitates.

PMID- 21852571
TI  - Chemical genetic strategy for targeting protein kinases based on covalent
      complementarity.
AB  - The conserved nature of the ATP-binding site of the > 500 human kinases renders
      the development of specific inhibitors a challenging task. A widely used chemical
      genetic strategy to overcome the specificity challenge exploits a large-to-small
      mutation of the gatekeeper residue (a conserved hydrophobic amino acid) and the
      use of a bulky inhibitor to achieve specificity via shape complementarity.
      However, in a number of cases, introduction of a glycine or alanine gatekeeper
      results in diminished kinase activity and ATP affinity. A new chemical genetic
      approach based on covalent complementarity between an engineered gatekeeper
      cysteine and an electrophilic inhibitor was developed to address these
      challenges. This strategy was evaluated with Src, a proto-oncogenic tyrosine
      kinase known to lose some enzymatic activity using the shape complementarity
      chemical genetic strategy. We found that Src with a cysteine gatekeeper
      recapitulates wild type activity and can be irreversibly inhibited both in vitro
      and in cells. A cocrystal structure of T338C c-Src with a vinylsulfonamide
      derivatized pyrazolopyrimidine inhibitor was solved to elucidate the inhibitor
      binding mode. A panel of electrophilic inhibitors was analyzed against 307
      kinases and MOK (MAPK/MAK/MRK overlapping kinase), one of only two human kinases
      known to have an endogenous cysteine gatekeeper. This analysis revealed
      remarkably few off-targets, making these compounds the most selective chemical
      genetic inhibitors reported to date. Protein engineering studies demonstrated
      that it is possible to increase inhibitor potency through secondary-site
      mutations. These results suggest that chemical genetic strategies based on
      covalent complementarity should be widely applicable to the study of protein
      kinases.

PMID- 21852573
TI  - Permafrost carbon-climate feedbacks accelerate global warming.
AB  - Permafrost soils contain enormous amounts of organic carbon, which could act as a
      positive feedback to global climate change due to enhanced respiration rates with
      warming. We have used a terrestrial ecosystem model that includes permafrost
      carbon dynamics, inhibition of respiration in frozen soil layers, vertical mixing
      of soil carbon from surface to permafrost layers, and CH(4) emissions from
      flooded areas, and which better matches new circumpolar inventories of soil
      carbon stocks, to explore the potential for carbon-climate feedbacks at high
      latitudes. Contrary to model results for the Intergovernmental Panel on Climate
      Change Fourth Assessment Report (IPCC AR4), when permafrost processes are
      included, terrestrial ecosystems north of 60 degrees N could shift from being a
      sink to a source of CO(2) by the end of the 21st century when forced by a Special
      Report on Emissions Scenarios (SRES) A2 climate change scenario. Between 1860 and
      2100, the model response to combined CO(2) fertilization and climate change
      changes from a sink of 68 Pg to a 27 + -7 Pg sink to 4 + -18 Pg source, depending
      on the processes and parameter values used. The integrated change in carbon due
      to climate change shifts from near zero, which is within the range of previous
      model estimates, to a climate-induced loss of carbon by ecosystems in the range
      of 25 + -3 to 85 + -16 Pg C, depending on processes included in the model, with a
      best estimate of a 62 + -7 Pg C loss. Methane emissions from high-latitude
      regions are calculated to increase from 34 Tg CH(4)/y to 41-70 Tg CH(4)/y, with
      increases due to CO(2) fertilization, permafrost thaw, and warming-induced
      increased CH(4) flux densities partially offset by a reduction in wetland extent.

PMID- 21852574
TI  - Identification and characterization of a functional mitochondrial angiotensin
      system.
AB  - The renin-angiotensin (Ang) system regulates multiple physiological functions
      through Ang II type 1 and type 2 receptors. Prior studies suggest an
      intracellular pool of Ang II that may be released in an autocrine manner upon
      stretch to activate surface membrane Ang receptors. Alternatively, an
      intracellular renin-Ang system has been proposed, with a primary focus on nuclear
      Ang receptors. A mitochondrial Ang system has not been previously described. Here
      we report that functional Ang II type 2 receptors are present on mitochondrial
      inner membranes and are colocalized with endogenous Ang. We demonstrate that
      activation of the mitochondrial Ang system is coupled to mitochondrial nitric
      oxide production and can modulate respiration. In addition, we present evidence
      of age-related changes in mitochondrial Ang receptor expression, i.e., increased
      mitochondrial Ang II type 1 receptor and decreased type 2 receptor density that
      is reversed by chronic treatment with the Ang II type 1 receptor blocker
      losartan. The presence of a functional Ang system in human mitochondria provides
      a foundation for understanding the interaction between mitochondria and chronic
      disease states and reveals potential therapeutic targets for optimizing
      mitochondrial function and decreasing chronic disease burden with aging.

PMID- 21852575
TI  - A stable hippocampal representation of a space requires its direct experience.
AB  - In humans and other mammals, the hippocampus is critical for episodic memory, the
      autobiographical record of events, including where and when they happen. When one
      records from hippocampal pyramidal neurons in awake, behaving rodents, their most
      obvious firing correlate is the animal's position within a particular
      environment, earning them the name "place cells." When an animal explores a novel
      environment, its pyramidal neurons form their spatial receptive fields over a
      matter of minutes and are generally stable thereafter. This experience-dependent
      stabilization of place fields is therefore an attractive candidate neural
      correlate of the formation of hippocampal memory. However, precisely how the
      animal's experience of a context translates into stable place fields remains
      largely unclear. For instance, we still do not know whether observation of a
      space is sufficient to generate a stable hippocampal representation of that space
      because the animal must physically visit a spot to demonstrate which cells fire
      there. We circumvented this problem by comparing the relative stability of place
      fields of directly experienced space from merely observed space following
      blockade of NMDA receptors, which preferentially destabilizes newly generated
      place fields. This allowed us to determine whether place cells stably represent
      parts of the environment the animal sees, but does not actually occupy. We found
      that the formation of stable place fields clearly requires direct experience with
      a space. This suggests that place cells are part of an autobiographical record of
      events and their spatial context, consistent with providing the "where"
      information in episodic memory.

PMID- 21852576
TI  - Quantification of sleep behavior and of its impact on the cross-talk between the
      brain and peripheral metabolism.
AB  - Rates of obesity have been steadily increasing, along with disorders commonly
      associated with obesity, such as cardiovascular disease and type II diabetes.
      Simultaneously, average sleep times have progressively decreased. Recently,
      evidence from both laboratory and epidemiologic studies has suggested that
      insufficient sleep may stimulate overeating and thus play a role in the current
      epidemic of obesity and diabetes. In the human sleep laboratory it is now
      possible to carefully control sleep behavior and study the link between sleep
      duration and alterations in circulating hormones involved in feeding behavior,
      glucose metabolism, hunger, and appetite. This article focuses on the
      methodologies used in experimental protocols that have examined modifications
      produced by sleep restriction (or extension) compared with normal sleep. The
      findings provide evidence that sleep restriction does indeed impair glucose
      metabolism and alters the cross-talk between the periphery and the brain,
      favoring excessive food intake. A better understanding of the adverse effects of
      sleep restriction on the CNS control of hunger and appetite may have important
      implications for public health.

PMID- 21852577
TI  - Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant
      chemotherapy response one day after starting treatment.
AB  - Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy
      fail to achieve a measurable response and endure toxic side effects without
      benefit. Most clinical and imaging measures of response are obtained several
      weeks after the start of therapy. Here, we report that functional hemodynamic and
      metabolic information acquired using a noninvasive optical imaging method on the
      first day after neoadjuvant chemotherapy treatment can discriminate nonresponding
      from responding patients. Diffuse optical spectroscopic imaging was used to
      measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and
      lipid in tumor and normal breast tissue of 24 tumors in 23 patients with
      untreated primary breast cancer. Measurements were made before chemotherapy, on
      day 1 after the first infusion, and frequently during the first week of therapy.
      Various multidrug, multicycle regimens were used to treat patients. Diffuse
      optical spectroscopic imaging measurements were compared with final postsurgical
      pathologic response. A statistically significant increase, or flare, in
      oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete
      responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare
      and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1
      was adequate to discriminate nonresponding tumors from responding tumors. Very
      early measures of chemotherapy response are clinically convenient and offer the
      potential to alter treatment strategies, resulting in improved patient outcomes.

PMID- 21852578
TI  - Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8)
      mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome.
AB  - Nakajo-Nishimura syndrome (NNS) is a disorder that segregates in an autosomal
      recessive fashion. Symptoms include periodic fever, skin rash, partial
      lipomuscular atrophy, and joint contracture. Here, we report a mutation in the
      human proteasome subunit beta type 8 gene (PSMB8) that encodes the
      immunoproteasome subunit beta5i in patients with NNS. This G201V mutation
      disrupts the beta-sheet structure, protrudes from the loop that interfaces with
      the beta4 subunit, and is in close proximity to the catalytic threonine residue.
      The beta5i mutant is not efficiently incorporated during immunoproteasome
      biogenesis, resulting in reduced proteasome activity and accumulation of
      ubiquitinated and oxidized proteins within cells expressing immunoproteasomes. As
      a result, the level of interleukin (IL)-6 and IFN-gamma inducible protein (IP)-10
      in patient sera is markedly increased. Nuclear phosphorylated p38 and the
      secretion of IL-6 are increased in patient cells both in vitro and in vivo, which
      may account for the inflammatory response and periodic fever observed in these
      patients. These results show that a mutation within a proteasome subunit is the
      direct cause of a human disease and suggest that decreased proteasome activity
      can cause inflammation.

PMID- 21852579
TI  - Minocycline-EDTA lock solution prevents catheter-related bacteremia in
      hemodialysis.
AB  - There is growing concern about the development of antibacterial resistance with
      the use of antibiotics in catheter lock solutions. The use of an antibiotic that
      is not usually used to treat other serious infections may be an alternative that
      may reduce the clinical impact should resistance develop. We conducted a
      randomized controlled trial to compare a solution of minocycline and EDTA with
      the conventional unfractionated heparin for the prevention of catheter-related
      bacteremia in hemodialysis patients during a period of 90 d. The study included
      204 incident catheters (27.8% tunneled); 14 catheters were excluded because of
      early dysfunction and 3 because of protocol violations. We observed catheter
      related bacteremia in 19 patients in the heparin group (4.3 per 1000 catheter
      days) and in 5 patients in the minocycline-EDTA group (1.1 per 1000 catheter
      days; P = 0.005). We did not detect a significant difference in the rate of
      catheter removal for dysfunction. Catheter-related bacteremia-free survival was
      significantly higher in the minocycline-EDTA group than in the heparin group (P =
      0.005). In conclusion, a minocycline-EDTA catheter lock solution is effective in
      the prevention of catheter-related bacteremia in hemodialysis patients.

PMID- 21852580
TI  - Nedd4-2 modulates renal Na+-Cl- cotransporter via the aldosterone-SGK1-Nedd4-2
      pathway.
AB  - Regulation of renal Na(+) transport is essential for controlling blood pressure,
      as well as Na(+) and K(+) homeostasis. Aldosterone stimulates Na(+) reabsorption
      by the Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) and
      by the epithelial Na(+) channel (ENaC) in the late DCT, connecting tubule, and
      collecting duct. Aldosterone increases ENaC expression by inhibiting the
      channel's ubiquitylation and degradation; aldosterone promotes serum
      glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin
      protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC
      interaction. It is important to note that aldosterone increases NCC protein
      expression by an unknown post-translational mechanism. Here, we present evidence
      that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at
      the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression
      of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant,
      strongly decreased NCC activity and surface expression. SGK1 prevented this
      inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in
      the renal tubules of mice and in cultured mDCT(15) cells upregulated NCC. In
      contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like
      motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did
      not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and
      abolished SGK1-dependent inhibition. Taken together, these results suggest that
      aldosterone modulates NCC protein expression via a pathway involving SGK1 and
      Nedd4-2 and provides an explanation for the well-known aldosterone-induced
      increase in NCC protein expression.

PMID- 21852581
TI  - Phosphate may promote CKD progression and attenuate renoprotective effect of ACE
      inhibition.
AB  - Phosphate may promote the onset and progression of chronic nephropathies. Here we
      evaluated the relationships between baseline serum phosphate levels, disease
      progression, and response to ACE inhibition in 331 patients with proteinuric
      nephropathies in the prospective Ramipril Efficacy In Nephropathy (REIN) trial.
      Independent of treatment, patients with phosphate levels in the highest two
      quartiles progressed significantly faster either to ESRD or to a composite
      endpoint of doubling of serum creatinine or ESRD compared with patients with
      phosphate levels below the median (P < 0.001). Results were similar when we
      analyzed phosphate as a continuous variable (P <= 0.004). The renoprotective
      effect of ramipril decreased as serum phosphate increased (P <= 0.008 for
      interaction); this modification of the treatment effect by phosphate persisted
      despite adjusting for potential confounders such as GFR and urinary protein. In
      summary, these data suggest that phosphate is an independent risk factor for
      progression of renal disease among patients with proteinuric CKD, and high levels
      of phosphate may even attenuate the renoprotective effect of ACE inhibitors.
      Future trials should test whether reducing serum phosphate improves renal
      outcomes and optimizes the renoprotective effect of ACE inhibition.

PMID- 21852582
TI  - Diagnostic value of urinary sodium, chloride, urea, and flow.
AB  - Up to 30% of hospitalized critically ill patients may have a rise in serum
      creatinine concentration. In addition to history and physical examination, there
      is diagnostic value in assessing urinary electrolytes, solute excretion, and
      urine flow in these patients. The correct interpretation of these urinary
      parameters can avoid unnecessary volume overload and mechanical ventilation, risk
      factors for increased mortality in patients with rising serum creatinine. The
      present article also discusses the role of arterial underfilling in causing
      prerenal azotemia in the presence of an increase in total body sodium and
      extracellular fluid expansion. As with extracellular fluid volume depletion,
      arterial underfilling secondary to impaired cardiac function or primary arterial
      vasodilation can delay or prevent recovery from ischemic or toxic acute tubular
      necrosis. The present brief review discusses the various aspects of the correct
      interpretation of urinary electrolytes, solute excretion, and urine flow in the
      setting of a rising serum creatinine concentration.

PMID- 21852583
TI  - Effect of recommendations from reviewers suggested or excluded by authors.
AB  - The Journal of the American Society of Nephrology (JASN) gives authors submitting
      original research the option of suggesting qualified reviewers or those they wish
      to exclude. This historical habit often leaves us wondering whether author
      preferences correlate with reviewer recommendations and whether differences
      related to reviewer selection affect decisions by editors. In a self-study
      presented here, we found that author-suggested reviewers, as a group, make more
      positive recommendations than editor-suggested reviewers (P = 0.01), although the
      difference disappears when recommendations are compared with those of editor
      suggested reviewers of the same manuscript (P = 0.081). The distribution of
      recommendations by author-excluded reviewers, as a group, did not differ from
      those by editor-suggested reviewers; however, author-excluded reviewers impart
      significantly more negative recommendations than other reviewers of the same
      manuscript (P = 0.029). We further explored whether such differences result from
      individual reviewer tendencies to give generally more positive or more negative
      recommendations than editor-suggested reviewers and found no such tendency.
      Finally, editorial decisions on manuscripts reviewed by author-suggested or
      author-excluded reviewers do not differ from those decisions on manuscripts
      assigned but not reviewed by them. JASN's policy of editors making decisions
      independent from individual reviewer recommendations minimizes the effect of
      selection bias on publication decisions.

PMID- 21852584
TI  - Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23
      klotho in chronic kidney disease.
AB  - There is increasingly evidence that the interactions between vitamin D,
      fibroblast growth factor 23 (FGF-23), and klotho form an endocrine axis for
      calcium and phosphate metabolism, and derangement of this axis contributes to the
      progression of renal disease. Several recent studies also demonstrate negative
      regulation of the renin gene by vitamin D. In chronic kidney disease (CKD), low
      levels of calcitriol, due to the loss of 1-alpha hydroxylase, increase renal
      renin production. Activation of the renin-angiotensin-aldosterone system (RAAS),
      in turn, reduces renal expression of klotho, a crucial factor for proper FGF-23
      signaling. The resulting high FGF-23 levels suppress 1-alpha hydroxylase, further
      lowering calcitriol. This feedback loop results in vitamin D deficiency, RAAS
      activation, high FGF-23 levels, and renal klotho deficiency, all of which
      associate with progression of renal damage. Here we examine current evidence for
      an interaction between the RAAS and the vitamin D-FGF-23-klotho axis as well as
      its possible implications for progression of CKD.

PMID- 21852585
TI  - Osmosensory mechanisms in cellular and systemic volume regulation.
AB  - Perturbations of cellular and systemic osmolarity severely challenge the function
      of all organisms and are consequently regulated very tightly. Here we outline
      current evidence on how cells sense volume perturbations, with particular focus
      on mechanisms relevant to the kidneys and to extracellular osmolarity and whole
      body volume homeostasis. There are a variety of molecular signals that respond to
      perturbations in cell volume and osmosensors or volume sensors responding to
      these signals. The early signals of volume perturbation include integrins, the
      cytoskeleton, receptor tyrosine kinases, and transient receptor potential
      channels. We also present current evidence on the localization and function of
      central and peripheral systemic osmosensors and conclude with a brief look at the
      still limited evidence on pathophysiological conditions associated with deranged
      sensing of cell volume.

PMID- 21852588
TI  - Immediate-release oxybutynin for the treatment of clozapine-induced sialorrhea.
AB  - OBJECTIVE: To describe a case of clozapine-induced sialorrhea alleviated by
      immediate-release oxybutynin. CASE SUMMARY: A 53-year-old female with
      schizoaffective disorder-bipolar type was admitted to a psychiatric unit and
      initiated on clozapine. During titration to a dose of 300 mg daily and despite
      taking concomitant oral benztropine 1 mg twice daily, the patient began to
      experience mild sialorrhea. The sialorrhea became profuse when the clozapine dose
      reached 400 mg daily, and the patient was routinely seen with a saliva-soaked
      shirt. Additionally, she had become self-conscious and wanted to stop clozapine
      therapy. Immediate-release oxybutynin 5 mg daily was started, resulting in
      significant reduction of the sialorrhea within 24 hours. The patient was
      discharged on clozapine 300 mg daily, risperidone 6 mg at bedtime, immediate
      release oxybutynin 5 mg twice daily, and oral benztropine 1.5 mg daily, with only
      mild sialorrhea. DISCUSSION: It is unknown why clozapine induces sialorrhea. One
      speculation is that clozapine interrupts muscarinic receptor homeostasis.
      Immediate-release oxybutynin is an anticholinergic agent with high affinity for
      salivary gland M3 receptors that may have restored muscarinic receptor imbalance
      in our patient. N-Desethyl-oxybutynin, an active metabolite of oxybutynin, is
      largely responsible for oxybutynin's anticholinergic activity. The activity of
      oxybutynin and its metabolite may result in dry mouth in over 80% of patients
      taking the immediate-release formulation, while producing dry mouth in only 40%
      and 7.5% of patients taking the extended-release and topical formulations,
      respectively. CONCLUSIONS: To our knowledge, this is the first report of
      immediate-release oxybutynin successfully reducing clozapine-induced sialorrhea.
      If oxybutynin is considered for this indication, use of the immediate-release
      formulation seems prudent. Additional data, including randomized controlled
      trials, are needed to confirm whether immediate-release oxybutynin has a
      significant role in the management of this stigmatizing adverse effect.

PMID- 21852586
TI  - Smad3-mediated upregulation of miR-21 promotes renal fibrosis.
AB  - TGF-beta/Smad signaling plays a role in fibrogenesis, but therapies targeting TGF
      beta are ineffective in treating renal fibrosis. Here, we explored the
      therapeutic potential of targeting TGF-beta-induced microRNA in the progression
      of renal fibrosis. Microarray analysis and real-time PCR revealed upregulation of
      miR-21 in tubular epithelial cells (TECs) in response to TGF-beta. Lack of Smad3,
      but not lack of Smad2, prevented cells from upregulating miR-21 in response to
      TGF-beta. In addition, Smad3-deficient mice were protected from upregulation of
      miR-21 and fibrosis in the unilateral ureteral obstruction model. In contrast,
      conditional knockout of Smad2 enhanced miR-21 expression and renal fibrosis.
      Furthermore, ultrasound-microbubble-mediated gene transfer of a miR-21-knockdown
      plasmid halted the progression of renal fibrosis in established obstructive
      nephropathy. In conclusion, these data demonstrate that Smad3, but not Smad2,
      signaling increases expression of miR-21, which promotes renal fibrosis.
      Inhibition of miR-21 may be a therapeutic approach to suppress renal fibrosis.

PMID- 21852591
TI  - Domperidone-induced tardive dyskinesia and withdrawal psychosis in an elderly
      woman with dementia.
AB  - OBJECTIVE: To report a case of probable domperidone-induced tardive dyskinesia
      and withdrawal psychosis in an elderly woman. CASE SUMMARY: A 75-year-old woman
      was first assessed for cognitive decline and personality changes. On clinical
      examination, diffuse choreoathetoid movements were noted. Chronic domperidone use
      seemed the most likely cause for the movement disorder and was abruptly
      discontinued. Within a few days, she developed a severe psychotic syndrome with
      Capgras delusions; the movement disorder continued unabated. Both the movement
      disorder and psychotic symptoms promptly remitted with risperidone treatment.
      DISCUSSION: Domperidone has, on rare occasions, been associated with acute
      extrapyramidal syndromes, especially in young children, but, to our knowledge,
      this is the first case of domperidone-induced tardive dyskinesia and withdrawal
      psychosis, adverse effects associated with chronic central nervous system
      dopaminergic blockade. Domperidone is a dopamine D2 receptor antagonist that does
      not usually cross the blood-brain barrier. However, blood-brain barrier
      alterations occur with aging and dementia, which may explain central nervous
      system penetration of domperidone in our patient, diagnosed with probable
      frontotemporal dementia. The association was rated as probable on the Naranjo
      probability scale. CONCLUSIONS: Chronic use of domperidone may, on rare
      occasions, induce neuropsychiatric syndromes similar to those seen with the use
      of antipsychotics. This may be more likely in situations in which the blood-brain
      barrier is damaged, as in vascular and degenerative dementias.

PMID- 21852592
TI  - Lubiprostone for constipation in adults with cystic fibrosis: a pilot study.
AB  - BACKGROUND: Constipation is prevalent in the cystic fibrosis (CF) population and
      yet there are few data demonstrating the effectiveness of currently used
      treatments. Lubiprostone is a laxative that works by activating the type 2
      chloride channel in the gastrointestinal tract and thus has the potential to be
      especially effective for constipation associated with CF. OBJECTIVE: To evaluate
      the effectiveness of lubiprostone for the treatment of constipation in adults
      with CF. METHODS: In this pilot study, participants acted as their own controls
      and comparisons were made between run-in and treatment periods. During the 2-week
      run-in period, participants continued their usual treatment for constipation;
      during the 4-week treatment period, participants received lubiprostone 24 MUg
      twice daily. Efficacy outcomes included spontaneous bowel movement frequency,
      Bristol Stool Scale scores, and Patient Assessment of Constipation Symptoms (PAC
      SYM) survey scores. Outcomes were assessed during both the run-in and treatment
      periods (0, 2, and 4 weeks of treatment). Safety outcomes included spirometry,
      body weight, and serum chemistry. RESULTS: Seven participants completed the
      study. Mean (SD) baseline forced expiratory volume in 1 second was 83.0% (9.4) of
      predicted and body mass index was 24.0 (2.8) kg/m2, indicating an overall
      healthy, well-nourished group of adults with CF. Lubiprostone improved overall
      symptoms of constipation as measured by PAC-SYM survey scores (1.18 [0.56], 0.54
      [0.27], and 0.44 [0.36] at 0, 2, and 4 weeks, respectively; p < 0.001).
      Spontaneous bowel movement frequency and Bristol Stool Scale scores were not
      statistically significantly different between periods. There were no differences
      in safety measures. Transient chest tightness and shortness of breath were
      reported by 2 separate participants, although neither participant withdrew due to
      these adverse effects. CONCLUSIONS: Lubiprostone may be an effective option for
      the treatment of constipation in adults with CF.

PMID- 21852593
TI  - Baseline and follow-up laboratory monitoring of cardiovascular medications.
AB  - BACKGROUND: Laboratory monitoring of medications is typically used to establish
      safety prior to drug initiation and to detect drug-related injury following
      initiation. It is unclear whether black box warnings (BBWs) as well as evidence-
      and consensus-based clinical guidelines increase the likelihood of appropriate
      monitoring. OBJECTIVE: To determine the proportion of patients newly initiated on
      selected cardiovascular medications with baseline assessment and follow-up
      laboratory monitoring and compare the prevalence of laboratory testing for drugs
      with and without BBWs and guidelines. METHODS: This cross-sectional study
      included patients aged 18 years or older from a large multispecialty group
      practice who were prescribed a cardiovascular medication (angiotensin converting
      enzyme inhibitors, angiotensin II receptor blockers, amiodarone, digoxin, lipid
      lowering agents, diuretics, and potassium supplements) between January 1 and July
      31, 2008. The primary outcome measure was laboratory test ordering for baseline
      assessment and follow-up monitoring of newly initiated cardiovascular
      medications. RESULTS: The number of new users of each study drug ranged from 49
      to 1757 during the study period. Baseline laboratory test ordering across study
      drugs ranged from 37.4% to 94.8%, and follow-up laboratory test ordering ranged
      from 20.0% to 77.2%. Laboratory tests for drugs with baseline laboratory
      assessment recommendations in BBWs were more commonly ordered than for drugs
      without BBWs (86.4% vs 78.0%, p < 0.001). Drugs with follow-up monitoring
      recommendations in clinical guidelines had a lower prevalence of monitoring
      (33.1% vs 50.7%, p < 0.001). CONCLUSIONS: Baseline assessment of cardiovascular
      medication monitoring is variable. Quality measurement of adherence to BBW
      recommendations may improve monitoring.

PMID- 21852596
TI  - Dapsone-induced methemoglobinemia: a primer for clinicians.
AB  - OBJECTIVE: To present a comprehensive review of dapsone-induced methemoglobinemia
      and its management. DATA SOURCES: Literature retrieval was accessed through
      MEDLINE (1966-March 2011), Cochrane Library, and EMBASE, using the terms dapsone
      and methemoglobinemia. STUDY SELECTION AND DATA EXTRACTION: All case reports,
      small case series, and randomized controlled trials published in English were
      evaluated. Because of the absence of comprehensive updates on this topic since
      1996, publications between 1997 and March 2011 were included in this review. DATA
      SYNTHESIS: Between 1997 and March 2011, the majority of publications describing
      methemoglobinemia associated with dapsone use reported this adverse effect at
      therapeutic doses. Excluding overdose situations, 18 described symptomatic
      dapsone-associated methemoglobinemia and clinical presentation ranging from
      cyanosis to dyspnea. In almost all of the accounts, patients had a concurrent
      event such as anemia or pneumonia, suggesting an interplay between these
      comorbidities and the onset of symptomatic methemoglobinemia. Delayed hemolytic
      anemia was seen in patients with high methemoglobin levels at presentation.
      Management in most cases consisted of administration of methylene blue. Overall,
      most reports described a successful outcome, and no mortality resulted from
      methemoglobinemia associated with therapeutic use. CONCLUSIONS: Clinicians should
      recognize methemoglobinemia as an adverse effect associated with dapsone use and
      the potential factors that precipitate it. They should also know how to promptly
      and effectively manage this event.

PMID- 21852597
TI  - Treating hypertension in the very elderly.
AB  - OBJECTIVE: To review the evidence for strict blood pressure (BP) management in
      the very elderly, defined as patients aged 80 years and older. DATA SOURCES: A
      literature search was performed using PubMed (1950 through November 2010) for the
      MeSH terms hypertension and elderly; subterms of identified MeSH terms (ie,
      explosion) for the elderly were also searched. A broader search was conducted of
      PubMed articles published in the past 4 years. Searches were conducted for
      additional primary literature referenced in identified articles; an updated
      Cochrane Database review was also performed. STUDY SELECTION AND DATA EXTRACTION:
      All identified studies that specifically included very elderly patients and BP
      were reviewed. DATA SYNTHESIS: The BP goal established in the Seventh Report of
      the Joint National Committee on Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure (JNC 7) is less than 140/90 mm Hg, regardless of age,
      unless a compelling indication exists. Although evidence suggests that lowering
      BP will lower the risk of stroke, lower BP in the very elderly may result in
      higher mortality. Many physicians are reluctant to treat BP in accordance with
      the JNC 7 goal in very elderly patients for a variety of reasons, including
      concerns about fall risk, lack of benefit in mortality reduction, and concerns
      about drug interactions and adverse effects. Results from a randomized controlled
      trial and meta-analysis have demonstrated reductions in stroke, heart failure,
      and cardiovascular events in the very elderly. The American College of Cardiology
      Foundation/American Heart Association recently published guidelines for elderly
      patients that suggest treating the very elderly carefully and with different BP
      goals than previously recommended. CONCLUSIONS: Optimal management of
      hypertension in the very elderly remains a concern. Few studies have evaluated
      hypertension in this population, and studies that included patients over 80
      enrolled too few to draw conclusions. Although the HYVET (Hypertension in the
      Very Elderly Trial) study did have adequate power to evaluate the very elderly,
      because this study was stopped early because of significant findings in
      mortality, unanswered questions remain regarding optimal BP targets.

PMID- 21852598
TI  - Importance of including early nonadherence in estimations of medication
      adherence.
AB  - BACKGROUND: Many medication adherence metrics are based on refill rates
      determined from pharmacy claims databases. However, these methods do not
      incorporate assessment of nonadherence to new prescriptions when those
      prescriptions are never dispensed (primary nonadherence), or dispensed only once
      (early nonpersistence). As a result, published studies may overestimate
      adherence, but the extent of overestimation posed by not considering patients
      with primary nonadherence and early nonpersistence has not been assessed.
      OBJECTIVE: To estimate the magnitude of misestimation in adherence estimates that
      results from not including patients with primary nonadherence and early
      nonpersistence. METHODS: We conducted a retrospective cohort study of 15,417
      patients enrolled in an integrated health care delivery system who were newly
      prescribed an antihypertensive, antidiabetic, or antihyperlipidemic medication.
      We linked prescription orders to medication dispensings. Based on dispensing and
      refill rates, we stratified patients into primary nonadherent, early
      nonpersistent, and ongoing dispensings groups. Adherence was estimated using the
      proportion of days covered (PDC). Standardized observation periods were applied
      across all groups. RESULTS: A total of 1142 (7.4%) patients were primarily
      nonadherent, 3356 (21.8%) demonstrated early nonpersistence, and 10,919 (70.8%)
      patients received ongoing dispensings, with a mean PDC of 84%. Not including
      primarily nonadherent and early nonpersistent patients in calculations resulted
      in adherence estimates overestimated by 9-18%. CONCLUSIONS: When medication
      adherence is estimated from pharmacy claims databases, adherence estimates are
      substantially inflated because primarily nonadherent and early nonpersistent
      patients are not included in the estimations. An implication of this incorrect
      estimation is potential distortion of the true relationship between medication
      adherence and clinical outcomes.

PMID- 21852599
TI  - P2Y12 receptor inhibitors: integrating ticagrelor into the management of acute
      coronary syndrome.
AB  - Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST
      segment elevation ACS and ST-segment elevation myocardial infarction. The purpose
      of this article is to define the developing role of ticagrelor in ACS and compare
      it to currently available P2Y12 receptor inhibitors. While clopidogrel remains
      the "workhorse" P2Y12 receptor inhibitor for many patients with ACS and prasugrel
      has an established role in select situations, clinicians must now assimilate the
      evolving role of ticagrelor. Although ticagrelor offers important advances in the
      management of ACS (eg, reversibility), there are also notable clinical
      considerations (eg, unique adverse effects such as dyspnea). Based on the current
      evidence, we propose an algorithm to aid clinicians in the selection of a P2Y12
      receptor inhibitor for patients with ACS in various clinical situations.

PMID- 21852600
TI  - Comment: economic impact of therapeutic substitution of a brand selective
      serotonin reuptake inhibitor with an alternative generic selective serotonin
      reuptake inhibitor in patients with major depressive disorder.

PMID- 21852601
TI  - Technological advances in the management of unruptured intracranial aneurysms
      fail to improve outcome in New York state.
AB  - BACKGROUND AND PURPOSE: Unruptured intracranial aneurysms (UIAs) are being
      identified more frequently and endovascular coil embolization has become an
      increasingly popular treatment modality. Our study evaluates patient outcomes
      with changing patterns of treatment of UIA. METHODS: We conducted a
      retrospective, longitudinal cohort study of 3132 hospital discharges for UIA
      identified from the New York Statewide Database (SPARCS) in 2005 to 2007 and 2200
      discharges from 1995 to 2000. The rates of endovascular coiling and surgical
      clipping were examined along with hospital variables and discharge outcome.
      Anatomic specifics of UIA were unavailable for analysis. RESULTS: The case rate
      for treatment of UIA doubled from 1.59 (1995 to 2000) to 3.45 per 100,000 (2005
      to 2007, P<0.0001) and increased in the case treatment rate for coiling of UIA
      (0.36 versus 1.98 per 100,000, P<0.0001). Compared with the old epoch, there were
      more UIAs clipped at high-volume centers (55.8% versus 78.8%, P<0.0001) but fewer
      coiled at high-volume centers (94.8% versus 84.5%, P<0.0001) in the new epoch.
      Coiling and increasing hospital UIA treatment volume were associated with good
      discharge outcome. However, there was no significant improvement in overall good
      outcome when comparing 1995 to 2000 versus 2005 to 2007 (79% versus 81%, P=0.168)
      and a worsening of good outcomes for clipping (76.3% versus 71.7%, P=0.0132).
      CONCLUSIONS: Despite coiling being associated with an increased incidence of good
      outcome relative to clipping of UIA, the increase in coiling has failed to
      improve overall patient outcome. The shift in coiling venue from high-volume
      centers to low-volume centers and decreasing microsurgical volume accompanied by
      a worsening in microsurgical results contribute to this. This argues for greater
      centralization of care.

PMID- 21852602
TI  - Microembolism versus hemodynamic impairment in rosary-like deep watershed
      infarcts: a combined positron emission tomography and transcranial Doppler study.
AB  - BACKGROUND AND PURPOSE: Deep watershed infarcts are frequent in high-grade
      carotid disease and are thought to result from hemodynamic impairment,
      particularly when adopting a rosary-like pattern. However, a role for
      microembolism has also been suggested, though never directly tested. Here, we
      studied the relationships among microembolic signals (MES) on transcranial
      Doppler, rosary-like deep watershed infarcts on brain imaging, and cerebral
      hemodynamic compromise on positron emission tomography (PET), all in severe
      symptomatic carotid disease. We hypothesized that rosary-like infarcts would be
      significantly associated with worse hemodynamic status, independent of the
      presence of MES. METHODS: Sixteen patients with >=70% carotid disease ipsilateral
      to recent transient ischemic attack/minor stroke underwent magnetic resonance
      imaging including diffusion-weighted imaging, (15)O-PET, and transcranial
      Doppler. Mean transit time, a specific marker for hemodynamic impairment, was
      obtained in the symptomatic and unaffected hemispheres. RESULTS: Eleven of 16
      patients had rosary-like infarcts (Rosary+) and 8 patients had MES. Mean transit
      time was significantly higher (P=0.008) in Rosary+ patients than in healthy
      controls (n=10), and prevalence of MES was not different between Rosary+ and
      Rosary- patients. Contrary to our hypothesis, however, the presence of MES within
      the Rosary+ subset was associated (P=0.03) with a better hemodynamic status than
      in their absence, with a significant (P=0.02) negative correlation between mean
      transit time and rate of MES/h. CONCLUSIONS: Contrary to mainstream
      understanding, rosary-like infarcts were not independent of presence and rate of
      MES, suggesting that microembolism plays a role in their pathogenesis, probably
      in association with hemodynamic impairment. Pending confirmation in a larger
      sample, these findings have management implications for patients with carotid
      disease and rosary-like infarcts.

PMID- 21852603
TI  - Letter by Markl and Harloff regarding article, "Right-left propensity and lesion
      patterns between cardiogenic and aortogenic cerebral embolisms".

PMID- 21852604
TI  - Chronic kidney disease and drinking status in relation to risks of stroke and its
      subtypes: the Circulatory Risk in Communities Study (CIRCS).
AB  - BACKGROUND AND PURPOSE: Several epidemiological studies have established an
      association between chronic kidney disease (CKD), based on estimated glomerular
      filtration rate (GFR), and risk of stroke. However, sex-specific evidence for the
      relationship between CKD and risk of stroke and its subtypes is still limited.
      METHODS: We conducted a prospective cohort study of 12 222 Japanese men and women
      age 40 to 69 years living in 4 communities under systematic surveillance of
      stroke incidence to determine the relationship between CKD and risk of stroke and
      its subtypes. RESULTS: During the 17-year follow-up, there were 566 strokes (327
      ischemic and 186 hemorrhagic strokes). GFR was inversely associated with age- and
      community-adjusted risk of total stroke for both men and women. Compared with the
      reference group without CKD (GFR >=60 mL/min per 1.73m(2)), the adjusted risks of
      total stroke for subjects with CKD (GFR <60 mL/min per 1.73m(2)) were 1.63 (1.22
      2.17) for men and 1.51 (1.13-2.02) for women. Excess risk of stroke associated
      with CKD was identified primarily for hemorrhagic stroke among men and for
      ischemic stroke among women. After adjustment for traditional cardiovascular risk
      factors, associations remained statistically significant. When stratified by
      drinking status, excess risk of hemorrhagic stroke with CKD was confined to
      drinkers; adjusted risks were 4.18 (2.31-7.57) for men and 7.00 (1.92-25.56) for
      women. CONCLUSIONS: CKD was associated with increased risk of hemorrhagic stroke
      for men, and of ischemic stroke for women. This sex difference may partly be
      explained by the difference in prevalence of drinkers between men and women.

PMID- 21852605
TI  - Prevalence and prognosis of asymptomatic vertebral artery origin stenosis in
      patients with clinically manifest arterial disease.
AB  - BACKGROUND AND PURPOSE: The risk of ischemic stroke in patients with asymptomatic
      vertebral artery stenosis is unknown. We examined the incidence of posterior
      circulation ischemic stroke in patients with asymptomatic stenosis of the
      vertebral artery origin (VAo). METHODS: We studied a hospital-based cohort of
      3717 patients (median age, 60 years; interquartile range, 52 to 68 years) with
      atherosclerotic arterial disease enrolled in the Second Manifestations of
      ARTerial disease (SMART) study. We included patients in whom duplex ultrasound of
      the carotid artery and vertebral artery had been performed. Patients with
      symptomatic VAo stenosis or planned revascularization of the carotid artery or
      vertebral artery were excluded. Data were analyzed with Cox regression; hazard
      ratios were adjusted for age and vascular risk factors. RESULTS: In 282 patients
      (7.6%), asymptomatic VAo stenosis>50% was diagnosed with duplex ultrasound.
      During a mean follow-up of 4.6 years (SD, 3.0), posterior circulation ischemic
      stroke occurred in 5 of the 282 patients with asymptomatic VAo stenosis at
      baseline (annual stroke rate, 0.4%) and in 12 of the 3435 patients without VAo
      stenosis (annual stroke rate, <0.1%). The risk of posterior circulation ischemic
      stroke was higher in patients with VAo stenosis than in patients without VAo
      stenosis (hazard ratio, 4.2; 95% CI, 1.4 to 13.1) and was further increased in
      patients with both VAo and carotid artery stenosis (hazard ratio, 10.5; 95% CI,
      3.0 to 37.3). In multivariable analysis, this risk remained essentially the same.
      CONCLUSIONS: Patients with atherosclerotic arterial disease and asymptomatic VAo
      stenosis have a higher risk of posterior circulation ischemic stroke than
      patients without such a stenosis, but the absolute risk remains low.

PMID- 21852606
TI  - Inhibition of protein kinase Cbeta reverses increased blood-brain barrier
      permeability during hyperglycemic stroke and prevents edema formation in vivo.
AB  - BACKGROUND AND PURPOSE: We investigated the effect of circulating factors and
      protein kinase Cbeta on blood-brain barrier permeability and edema during
      hyperglycemic stroke. METHODS: Male Wistar rats that were hyperglycemic by
      streptozotocin (50 mg/kg) for 5 to 6 days underwent middle cerebral artery
      occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Blood-brain barrier
      permeability was measured in middle cerebral arteries that were ischemic (MCAO)
      or nonischemic (CTL) and perfused with plasma (20% in buffer) from MCAO or CTL
      animals. A separate set of MCAO vessels was perfused with the protein kinase
      Cbeta inhibitor CGP53353 (0.5 MUmol/L) and permeability measured. Lastly,
      hyperglycemic rats were treated intravenously with CGP53353 (10 or 100 MUg/kg or
      vehicle 15 minutes before reperfusion and edema formation measured by wet:dry
      weights (n=6/group). RESULTS: MCAO vessels had increased permeability compared
      with controls regardless of the plasma perfusate. Permeability (water flux,
      MUm(3)*10(8)) of CTL vessel/CTL plasma (n=8), CTL vessel/MCAO plasma (n=7), MCAO
      vessel/CTL plasma (n=6), and MCAO vessel/MCAO plasma (n=6) was 0.98+/-0.11,
      1.13+/-0.07, 1.36+/-0.02, and 1.34+/-0.06; P<0.01). Inhibition of protein kinase
      Cbeta in MCAO vessels (n=6) reversed the increase in permeability (0.92+/-0.1;
      P<0.01). In vivo, hyperglycemia increased edema versus normoglycemia after MCAO
      (water content=78.84%+/-0.11% versus 81.38%+/-0.21%; P<0.01). Inhibition of
      protein kinase Cbeta with 10 or 100 MUg/kg CGP53353 during reperfusion prevented
      the increased edema in hyperglycemic animals (water content=79.54%+/-0.56% and
      79.99%+/-0.43%; P<0.01 versus vehicle). CONCLUSIONS: These results suggest that
      the pronounced vasogenic edema that occurs during hyperglycemic stroke is
      mediated in large part by activation of protein kinase Cbeta.

PMID- 21852607
TI  - Optimizing protocols for risk prediction in asymptomatic carotid stenosis using
      embolic signal detection: the Asymptomatic Carotid Emboli Study.
AB  - BACKGROUND AND PURPOSE: Improved methods are required to identify patients with
      asymptomatic carotid stenosis at high risk for stroke. The Asymptomatic Carotid
      Emboli Study recently showed embolic signals (ES) detected by transcranial
      Doppler on 2 recordings that lasted 1-hour independently predict 2-year stroke
      risk. ES detection is time-consuming, and whether similar predictive information
      could be obtained from simpler recording protocols is unknown. METHODS: In a
      predefined secondary analysis of Asymptomatic Carotid Emboli Study, we looked at
      the temporal variation of ES. We determined the predictive yield associated with
      different recording protocols and with the use of a higher threshold to indicate
      increased risk (>=2 ES). To compare the different recording protocols,
      sensitivity and specificity analyses were performed using analysis of receiver
      operator characteristic curves. RESULTS: Of 477 patients, 467 had baseline
      recordings adequate for analysis; 77 of these had ES on 1 or both of the 2
      recordings. ES status on the 2 recordings was significantly associated
      (P<0.0001), but there was poor agreement between ES positivity on the 2
      recordings (kappa=0.266). For the primary outcome of ipsilateral stroke or
      transient ischemic attack, the use of 2 baseline recordings lasting 1 hour had
      greater predictive accuracy than either the first baseline recording alone
      (P=0.0005), a single 30-minute (P<0.0001) recording, or 2 recordings lasting 30
      minutes (P<0.0001). For the outcome of ipsilateral stroke alone, two recordings
      lasting 1 hour had greater predictive accuracy when compared to all other
      recording protocols (all P<0.0001). CONCLUSIONS: Our analysis demonstrates the
      relative predictive yield of different recording protocols that can be used in
      application of the technique in clinical practice. Two baseline recordings
      lasting 1 hour as used in Asymptomatic Carotid Emboli Study gave the best risk
      prediction.

PMID- 21852608
TI  - Activation of transient receptor potential vanilloid 1 by dietary capsaicin
      delays the onset of stroke in stroke-prone spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Previous studies show that endothelial nitric oxide
      synthase (eNOS) plays a prominent role in maintaining cerebral blood flow and
      preventing stroke. Capsaicin in hot pepper can increase the phosphorylation of
      eNOS in endothelial cells. We test the hypothesis that chronic dietary capsaicin
      can prevent stroke through activation of cerebrovascular transient receptor
      potential vanilloid 1 (TRPV1) channels in stroke-prone spontaneously hypertensive
      rats (SHRsp). METHODS: SHRsp were fed dietary capsaicin, and their onset of
      stroke was examined. TRPV1 knockout and transgenic mice were used for determining
      the function of TRPV1 channels. Expression of eNOS and cerebrovascular reactivity
      were examined. RESULTS: Immunofluorescence showed TRPV1 channels and eNOS
      coexpression in cerebral arterioles. Administration of capsaicin significantly
      increased phosphorylated eNOS in carotid arteries from wild-type mice but not in
      TRPV1 knockout mice. Inhibition of eNOS using N(G)-nitro-L-arginine methyl ester,
      removal of endothelium, or mutant TRPV1 significantly reduced capsaicin-induced
      endothelium-dependent relaxation of basilar arteries in mice. Chronic dietary
      capsaicin also remarkably increased eNOS expression in carotid arteries from
      SHRsp. Compared with Wistar-Kyoto rats, SHRsp had impaired endothelium-dependent
      relaxation of basilar arteries. Administration of capsaicin or L-arginine
      significantly improved the endothelium-dependent relaxation of basilar arteries
      in SHRsp. SHRsp had hypertrophy of cerebral arterioles, which was reversed by
      dietary capsaicin. Importantly, long-term administration of capsaicin
      significantly delayed the onset of stroke and increased the survival time in
      SHRsp. CONCLUSIONS: Activation of TRPV1 channels by dietary capsaicin mediated
      increases in phosphorylation of eNOS and could represent a novel target for
      dietary intervention of stroke.

PMID- 21852609
TI  - Safety of Tirofiban in acute Ischemic Stroke: the SaTIS trial.
AB  - BACKGROUND AND PURPOSE: Tirofiban is a highly selective, fast-acting nonpeptide
      glycoprotein IIb/IIIa platelet receptor antagonist with a short half-life time.
      Glycoprotein IIb/IIIa antagonists are effective for the treatment of acute
      coronary syndromes proven in large clinical trials. Safety and efficacy in
      patients with ischemic stroke are uncertain. This was addressed in the Safety of
      Tirofiban in acute Ischemic Stroke (SaTIS) trial. METHODS: Two hundred sixty
      patients with acute ischemic stroke were randomized in a placebo-controlled,
      prospective, open-label treatment, blinded outcome reading multicenter trial.
      Subjects with a National Institutes of Health Stroke Scale between 4 and 18
      received intravenously either tirofiban or placebo within 3 to 22 hours after
      symptom onset for 48 hours. The primary end point was the rate of cerebral
      bleeding as measured in follow-up CT scans 2 to 7 days after inclusion. The
      secondary end point was clinical efficacy within 1 week (National Institutes of
      Health Stroke Scale, modified Rankin Scale) and after 5 months (Barthel Index,
      modified Rankin Scale). RESULTS: The rate of cerebral hemorrhagic transformation
      (I/II) and parenchymal hemorrhage (I/II) did not differ between both groups
      (tirofiban 36 of 120; placebo 33 of 124: OR, 1.18; 95% CI, 0.66 to 2.06).
      Mortality after 5 months was significantly lower in patients treated with
      tirofiban (3 of 130 [2.3%] versus 11 of 126 [8.7%]; OR, 4.05; 95% CI, 1.1 to
      14.9). No difference in neurological/functional outcome was found after 1 week
      and after 5 months. CONCLUSIONS: We conclude that tirofiban might be safe in
      acute moderate ischemic stroke even when administered within a large time window
      after symptom onset and might save lives in the late outcome. Clinical Trial
      Registration- URL: www.strokecenter.org/trials/. Trial name: SaTIS. Enrollment
      began before July 1, 2005.

PMID- 21852610
TI  - Letter by Wong and Poon regarding article, "Does impaired cerebrovascular
      reactivity predict stroke risk in asymptomatic carotid stenosis? A prospective
      substudy of the Asymptomatic Carotid Emboli Study (ACES)".

PMID- 21852611
TI  - The inclusion of stroke in risk stratification for primary prevention of vascular
      events: the Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: The Framingham coronary heart disease (CHD) risk score
      estimates 10-year risk of myocardial infarction (MI) and CHD death. Because
      preventive approaches to CHD and stroke are similar, a composite outcome may be
      more appropriate. We compared 10-year risk of (1) MI or CHD death; and (2)
      stroke, MI, or CHD death among individuals free of vascular disease. METHODS: The
      Northern Manhattan Study contains a prospective, population-based study of stroke
      and CHD-free individuals>=40 years of age followed for a median of 10 years for
      vascular events. Framingham coronary heart disease risk score was calculated for
      each individual and for each category of predicted risk, Kaplan-Meier observed 10
      year cumulative probabilities were calculated for (1) MI or CHD death; and (2)
      stroke, MI, or CHD death. The cumulative probability of (1) was subtracted from
      (2), and 95% CIs for the difference were obtained with 1000 bootstrap samples.
      Using stratified analyses by race-ethnicity, we compared risk differences among
      race-ethnic groups. RESULTS: Among 2613 participants (53% Hispanic, 25% non
      Hispanic black, and 20% non-Hispanic white), observed 10-year risk of MI or CHD
      death was 14.20%. With stroke in the outcome, observed risk was 21.98% (absolute
      risk difference, 7.78%; 95% CI, 5.86% to 9.75%). The absolute risk difference
      among blacks was significantly larger than among whites (P=0.01). CONCLUSIONS: In
      this multiethnic urban population, adding stroke to the risk stratification
      outcome cluster resulted in a 55% relative increase in estimated risk and
      crossing of the absolute risk threshold (>20% over 10 years) considered for
      preventive treatments such as statins.

PMID- 21852612
TI  - Impact of the extended thrombolysis time window on the proportion of recombinant
      tissue-type plasminogen activator-treated stroke patients and on door-to-needle
      time.
AB  - BACKGROUND AND PURPOSE: The European Cooperative Acute Stroke Study (ECASS) III
      extended the thrombolysis time window for patients with stroke from 3 to 4.5
      hours after symptom onset. We investigated the effect of the extended
      thrombolysis time window on the proportion of recombinant tissue-type plasminogen
      activator-treated stroke patients and on the time of treatment initiation after
      hospital arrival. METHODS: The present study was based on a prospective database
      of 93 hospitals of the Stroke Register of Northwestern Germany, which included 91
      805 patients with ischemic stroke admitted between January 2007 and December
      2009. Main outcome measures were the use of recombinant tissue-type plasminogen
      activator among patients with stroke and the door-to-needle time before and after
      the publication of ECASS III in September 2008 and subsequent changes of the
      German guidelines in May 2009. RESULTS: Overall, 9262 patients (10.1%) were
      treated with recombinant tissue-type plasminogen activator. The proportion of
      thrombolyzed patients increased from 8.6% in 2007 to 11.7% in 2009. This increase
      was pronounced for patients admitted between 3 and 6 hours after symptom onset
      after the third quarter of 2008 (OR, 1.88; 95% CI, 1.24 to 2.85) and after the
      second and third quarters of 2009 (OR, 2.50; 95% CI, 1.69 to 3.69 and OR, 3.02;
      95% CI, 2.07 to 4.41) compared with the first half year 2007. The proportion of
      patients with stroke with a door-to-needle time<60 minutes increased after
      publication of ECASS III (OR, 1.49; 95% CI, 1.37 to 1.63). CONCLUSIONS: Results
      of ECASS III were rapidly implemented in routine stroke care. Concerns of a delay
      in recombinant tissue-type plasminogen activator treatment initiation after the
      extension of the thrombolysis time window were not confirmed.

PMID- 21852614
TI  - Diabetes and poor outcomes within 6 months after acute ischemic stroke: the China
      National Stroke Registry.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is an independent risk factor for
      ischemic stroke. However, controversy exists with regard to the impact of DM on
      prognosis after ischemic stroke in the Chinese population. We investigated the
      associations between DM and death, dependency, and stroke recurrence in patients
      after ischemic stroke onset in a nationwide, prospective registry, the China
      National Stroke Registry. METHODS: The China National Stroke Registry
      consecutively recruited patients hospitalized for acute ischemic stroke in 2007
      to 2008 and who were prospectively followed up for clinical and functional
      outcomes (death, dependency, and stroke recurrence) at 3 and 6 months after
      disease onset. Multivariable logistic regression was performed to analyze the
      association between DM and stroke outcomes after adjusting for potential
      confounding including age, sex, National Institutes of Health Stroke Scale score,
      glucose level at admission, hypertension, coronary heart disease, smoking,
      urinary tract infection, and other factors. RESULTS: DM was identified in 3483
      (27.0%) of stroke patients. Compared with stroke patients without DM, patients
      with DM had a significantly higher incidence of death or dependency and of
      recurrent stroke at 3 and 6 months after stroke onset. DM was an independent risk
      factor for death or dependency (adjusted odds ratio=1.23; 95% confidence
      interval, 1.10 to 1.37) in patients with ischemic stroke at 6 months after onset.
      CONCLUSIONS: DM independently predicted poor outcomes in Chinese patients after
      acute ischemic stroke.

PMID- 21852615
TI  - Multimodality monitoring for cerebral perfusion pressure optimization in comatose
      patients with intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Limited data exist to recommend specific cerebral
      perfusion pressure (CPP) targets in patients with intracerebral hemorrhage. We
      sought to determine the feasibility of brain multimodality monitoring for
      optimizing CPP and potentially reducing secondary brain injury after
      intracerebral hemorrhage. METHODS: We retrospectively analyzed brain
      multimodality monitoring data targeted at perihematomal brain tissue in 18
      comatose intracerebral hemorrhage patients (median monitoring, 164 hours).
      Physiological measures were averaged over 1-hour intervals corresponding to each
      microdialysis sample. Metabolic crisis was defined as a lactate/pyruvate ratio
      >40 with a brain glucose concentration <0.7 mmol/L. Brain tissue hypoxia (BTH)
      was defined as P(bt)O(2) <15 mm Hg. Pressure reactivity index and oxygen
      reactivity index were calculated. RESULTS: Median age was 59 years, median
      Glasgow Coma Scale score was 6, and median intracerebral hemorrhage volume was
      37.5 mL. The risk of BTH, and to a lesser extent metabolic crisis, increased with
      lower CPP values. Multivariable analyses showed that CPP <80 mm Hg was associated
      with a greater risk of BTH (odds ratio, 1.5; 95% confidence interval, 1.1-2.1;
      P=0.01) compared to CPP >100 mm Hg as a reference range. Six patients died (33%).
      Survivors had significantly higher CPP and P(bt)O(2) and lower ICP values
      starting on postbleed day 4, whereas lactate/pyruvate ratio and pressure
      reactivity index values were persistently lower, indicating preservation of
      aerobic metabolism and pressure autoregulation. CONCLUSIONS: P(bt)O(2) monitoring
      can be used to identify CPP targets for optimal brain tissue oxygenation. In
      patients who do not undergo multimodality monitoring, maintaining CPP >80 mm Hg
      may reduce the risk of BTH.

PMID- 21852616
TI  - Accumulation of dietary docosahexaenoic acid in the brain attenuates acute immune
      response and development of postischemic neuronal damage.
AB  - BACKGROUND AND PURPOSE: Consumption of fish has been shown to reduce risk of
      coronary heart disease and, possibly, of ischemic stroke. Because docosahexaenoic
      acid (DHA) is the most likely neuroactive component within fish oil, we
      hypothesized that exposing mice to a DHA-enriched diet may reduce inflammation
      and protect neurons against ischemic injury. METHODS: To visualize the effects of
      DHA on neuroinflammation after stroke, TLR2-fluc-GFP transgenic mice were exposed
      to either a control diet, a diet depleted in n-3 polyunsaturated fatty acid, or a
      diet enriched in DHA during 3 months. Real-time biophotonic/bioluminescence
      imaging of the TLR2 response was performed before and after middle cerebral
      artery occlusion, whereas cytokines concentrations and stroke area analyses were
      performed at 3 and 7 days after middle cerebral artery occlusion, respectively.
      RESULTS: We show that a 3-month DHA treatment prevented microglial activation
      after ischemic injury, reduced the ischemic lesion size, and increased levels of
      the antiapoptotic molecule Bcl-2 in the brain. Additional analysis revealed a
      significant decrease in the levels of COX2 and IL-1beta, but not in other
      proinflammatory cytokines. Importantly, long-term DHA supplementation
      significantly changed the n-3:n-6 polyunsaturated fatty acid ratio in the brain.
      CONCLUSIONS: Collectively, these data indicate that diet-induced accumulation of
      DHA in the brain protects against postischemic inflammation and injury. Because
      DHA is widely available at low cost and has an excellent safety profile, our data
      suggest that increased DHA intake may provide protection against acute immune
      response/brain damage in ischemic stroke.

PMID- 21852617
TI  - Value of carotid intima-media thickness and significant carotid stenosis as
      markers of stroke recurrence.
AB  - BACKGROUND AND PURPOSE: Data on the predictive value of carotid intima-media
      thickness (IMT) for stroke recurrence are scarce. We sought to analyze outcome
      differences in stroke patients with high IMT values compared with patients with
      significant carotid stenosis (SCS). METHODS: The multicenter observational ARTICO
      study included 620 independent patients older than 60 years with a first-ever
      noncardioembolic stroke. Patients were followed-up for 1 year. The primary end
      point was a composite of cardiovascular events and death. The IMT-ARTICO substudy
      analyzed ultrasonographic data from 599 patients. After Doppler carotid
      echography, patients were classified into the SCS group (carotid stenosis >=50%;
      117 cases), high IMT group (patients with the common carotid IMT in the highest
      quartile >=1.11 mm and without SCS; 110 cases), and control group (stroke
      patients with an IMT <1.11 mm and without SCS; 372 cases). We analyzed the impact
      of both conditions on the primary end point. RESULTS: During follow-up, 88
      patients (14.7%) had an end point event. Univariate analysis showed that male
      gender, diabetes, symptomatic peripheral arterial disease, ankle brachial index
      <=0.9, SCS, and high IMT were related to the primary end point. Cox regression
      showed that peripheral arterial disease (hazard ratio [HR], 2.06; 95% confidence
      interval [CI], 1.18-3.59; P=0.011), SCS (HR, 3.02; 95% CI, 1.78-5.13; P=0.0001),
      and high IMT (HR, 1.86; 95% CI, 1.05-3.29; P=0.032) were related to the primary
      end point. If patients with scheduled revascularization procedures were excluded
      from the Cox regression, then ultrasonographic markers were SCS (HR, 1.84; 95%
      CI, 1.03-3.28; P<0.039) and high IMT (HR, 1.86; 95% CI, 1.06-3.27; P=0.030).
      CONCLUSIONS: Both SCS and high IMT have an independent impact as markers of major
      cardiovascular events or death after a first-ever noncardioembolic stroke.

PMID- 21852618
TI  - Carbon monoxide-activated Nrf2 pathway leads to protection against permanent
      focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Carbon monoxide (CO) is a gaseous second messenger
      produced when heme oxygenase enzymes catabolize heme. We have demonstrated that
      CO can be therapeutic in ischemia-reperfusion brain injury; however, it is
      unclear whether CO can also offer protection in permanent ischemic stroke or what
      mechanism(s) underlies the effect. Heme oxygenase-1 neuroprotection was shown to
      be regulated by Nrf2; therefore, we investigated whether CO might partially exert
      neuroprotection by modulating the Nrf2 pathway. METHODS: To evaluate the
      potential protective effects of CO, we exposed male wild-type and Nrf2-knockout
      mice to 250 ppm CO or control air for 18 hours immediately after permanent middle
      cerebral artery occlusion. Infarct volume and neurologic deficits were assessed
      on day 7. Molecular mechanisms of Nrf2 pathway activation by CO were also
      investigated. RESULTS: Mice exposed to CO after permanent ischemia had 29.6+/
      12.6% less brain damage than did controls at 7 days, although amelioration in
      neurologic deficits did not reach significance. Additionally, 18-hour CO
      treatment led to Nrf2 dissociation from Keap1, nuclear translocation, increased
      binding activity of Nrf2 to heme oxygenase-1 antioxidant response elements, and
      elevated heme oxygenase-1 expression 6 to 48 hours after CO exposure. The CO
      neuroprotection was completely abolished in Nrf2-knockout mice. CONCLUSIONS: Low
      concentration CO represent a neuroprotective agent for combination treatment of
      ischemic stroke, and its beneficial effect would be at least partially mediated
      by activation of the Nrf2 pathway.

PMID- 21852619
TI  - Blood pressure management in acute stroke: does the Scandinavian Candesartan
      Acute Stroke Trial (SCAST) resolve all of the unanswered questions?

PMID- 21852621
TI  - Chronic kidney disease and alcohol consumption: are asians at particular risk for
      hemorrhagic stroke?

PMID- 21852620
TI  - Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for
      maximizing the use of intravenous thrombolytics and expanding treatment options
      with intra-arterial and neuroprotective therapies.
AB  - BACKGROUND AND PURPOSE: The goal of the Stroke Treatment Academic Industry
      Roundtable (STAIR) meetings is to advance the development of acute and
      restorative stroke therapies. Summary of Review- At the STAIR VII recommendations
      for strategies to maximize the use of intravenous thrombolytics through targeting
      public education, and the refinement of current treatment exclusion criteria were
      proposed. Increased utilization of mechanical devices for intra-arterial
      recanalization can be achieved by obtaining more definitive evidence of efficacy
      in randomized clinical trials, identification of patient characteristics
      associated with treatment efficacy, optimization of technical approaches,
      clarification of effective time windows, and development of approaches to limit
      complications. Neuroprotective strategies remain viable; recommendations for
      further study of these agents include an emphasis on rapid administration,
      consideration of the systemic effects of ischemic stroke, prevention of
      complications associated with early reperfusion, a focus on agents with multiple
      mechanisms of action, and consideration of possible interactions between
      neuroprotective and thrombolytic therapies. CONCLUSIONS: Extending intravenous
      thrombolysis to a broader patient population, clarifying the risk and benefits of
      intra-arterial reperfusion therapies, and further development of neuroprotective
      therapies were the key recommendations from STAIR VII.

PMID- 21852622
TI  - Cerebral oxygen transport failure?: decreasing hemoglobin and hematocrit levels
      after ischemic stroke predict poor outcome and mortality: STroke: RelevAnt Impact
      of hemoGlobin, Hematocrit and Transfusion (STRAIGHT)--an observational study.
AB  - BACKGROUND AND PURPOSE: Although conceivably relevant for penumbra oxygenation,
      the optimal levels of hemoglobin (Hb) and hematocrit (Hct) in patients with acute
      ischemic stroke are unknown. METHODS: We identified patients from our prospective
      local stroke database who received intravenous thrombolysis based on multimodal
      magnet resonance imaging during the years 1998 to 2009. A favorable outcome at 3
      months was defined as a modified Rankin Scale score<=2 and a poor outcome as a
      modified Rankin Scale score>=3. The dynamics of Hemoglobin (Hb), Hematocrit
      (Hct), and other relevant laboratory parameters as well as cardiovascular risk
      factors were retrospectively assessed and analyzed between these 2 groups.
      RESULTS: Of 217 patients, 114 had a favorable and 103 a poor outcome. In a
      multivariable regression model, anemia until day 5 after admission (odds ratio
      [OR]=2.61; 95% CI, 1.33 to 5.11; P=0.005), Hb nadir (OR=0.81; 95% CI, 0.67 to
      0.99; P=0.038), and Hct nadir (OR=0.93; 95% CI, 0.87 to 0.99; P=0.038) remained
      independent predictors for poor outcome at 3 months. Mortality after 3 months was
      independently associated with Hb nadir (OR=0.80; 95% CI, 0.65 to 0.98; P=0.028)
      and Hb decrease (OR=1.34; 95% CI, 1.01 to 1.76; P=0.04) as well as Hct decrease
      (OR=1.12; 95% CI, 1.01 to 1.23; P=0.027). CONCLUSIONS: Poor outcome and mortality
      after ischemic stroke are strongly associated with low and further decreasing Hb
      and Hct levels. This decrease of Hb and Hct levels after admission might be more
      relevant and accessible to treatment than are baseline levels.

PMID- 21852623
TI  - Examining whether dental therapists constitute a disruptive innovation in US
      dentistry.
AB  - Dental therapists-midlevel dental providers who are roughly analogous to nurse
      practitioners in medicine-might constitute a disruptive innovation within US
      dentistry. Proponents tend to claim that dental therapists will provide more
      equitable access to dental care; opponents tend to view them from a perspective
      that focuses on retaining the current attributes of the dental profession.
      Therapists display traits similar to those of disruptive innovations: their
      attributes are different from dentists', they may not initially be valued by
      current dental patients, they may appeal to current dental underutilizers, and
      they may transform the dental delivery system. Whether dental therapists
      constitute a disruptive innovation will only be determined retrospectively.

PMID- 21852624
TI  - Cultural context in the effort to improve oral health among Alaska Native people:
      the dental health aide therapist model.
AB  - The Alaska Native people in rural Alaska face serious challenges in obtaining
      dental care. Itinerant care models have failed to meet their needs for more than
      50 years. The dental health aide therapist (DHAT) model, which entails training
      midlevel care providers to perform limited restorative, surgical, and preventive
      procedures, was adopted to address some of the limitations of the itinerant
      model. We used quantitative and qualitative methods to assess residents'
      satisfaction with the model and the role of DHATs in the cultural context in
      which they operate. Our findings suggest that the DHAT model can provide much
      needed access to urgent care and is beneficial from a comprehensive cultural
      perspective.

PMID- 21852625
TI  - A systems perspective for dental health in older adults.

PMID- 21852626
TI  - The association between neighborhood characteristics and body size and physical
      activity in the California teachers study cohort.
AB  - OBJECTIVES: We considered interactions between physical activity and body mass
      index (BMI) and neighborhood factors. METHODS: We used recursive partitioning to
      identify predictors of low recreational physical activity (< 2.5 hours/week) and
      overweight and obesity (BMI >= 25.0 kg/m(2)) among 118,315 women in the
      California Teachers Study. Neighborhood characteristics were based on 2000 US
      Census data and Reference US business listings. RESULTS: Low physical activity
      and being overweight or obese were associated with individual sociodemographic
      characteristics, including race/ethnicity and age. Among White women aged 36 to
      75 years, living in neighborhoods with more household crowding was associated
      with a higher probability of low physical activity (54% vs 45% to 51%). In less
      crowded neighborhoods where more people worked outside the home, the existence of
      fewer neighborhood amenities was associated with a higher probability of low
      physical activity (51% vs 46%). Among non-African American middle-aged women,
      living in neighborhoods with a lower socioeconomic status was associated with a
      higher probability of being overweight or obese (46% to 59% vs 38% in high
      socioeconomic status neighborhoods). CONCLUSIONS: Associations between physical
      activity, overweight and obesity, and the built environment varied by
      sociodemographic characteristics in this educated population.

PMID- 21852627
TI  - Social gradients in oral health in older adults: findings from the English
      longitudinal survey of aging.
AB  - OBJECTIVES: We examined prospective associations between socioeconomic position
      (SEP) markers and oral health outcomes in a national sample of older adults in
      England. METHODS: Data were from the English Longitudinal Survey of Aging, a
      national cohort study of community-dwelling people aged 50 years and older. SEP
      markers (education, occupation, household income, household wealth, subjective
      social status, and childhood SEP) and sociodemographic confounders (age, gender,
      and marital status) were from wave 1. We collected 3 self-reported oral health
      outcomes at wave 3: having natural teeth (dentate vs edentate), self-rated oral
      health, and oral impacts on daily life. Using multivariate logistic regression
      models, we estimated associations between each SEP indicator and each oral health
      outcome, adjusted for confounders. RESULTS: Irrespective of SEP marker, there
      were inverse graded associations between SEP and edentulousness, with
      proportionately more edentate participants at each lower SEP level. Lower SEP was
      also associated with worse self-rated oral health and oral impacts among dentate,
      but not among edentate, participants. CONCLUSIONS: There are consistent and clear
      social gradients in the oral health of older adults in England, with disparities
      evident throughout the SEP hierarchy.

PMID- 21852628
TI  - US health care reform and the future of dentistry.
AB  - The Patient Protection and Affordable Care Act has grand ambitions: to provide
      insurance coverage to more than 30 million currently uninsured Americans, to slow
      increases in health care costs, to reorganize the health care delivery system,
      and to improve the quality of care provided to all. Where does the oral health
      community fit in this initiative? Should dentists "scope up" to become a more
      active part of the primary care workforce? Or should dentists "scope down" and
      delegate parts of the traditional dental tool kit to midlevel practitioners? Our
      nation's public health largely depends on whether we can create a more integrated
      and public health-oriented delivery system. The oral health, physical health, and
      public health communities should address this challenge together.

PMID- 21852629
TI  - Results of the Heart Healthy and Ethnically Relevant Lifestyle trial: a
      cardiovascular risk reduction intervention for African American women attending
      community health centers.
AB  - OBJECTIVES: We evaluated a theory-based lifestyle intervention targeting physical
      activity and dietary fat intake among African American women at high risk for
      cardiovascular disease. METHODS: The Heart Healthy and Ethnically Relevant
      Lifestyle trial (2005-2008) randomly assigned 266 low-income African American
      women aged 35 years and older who were patients of South Carolina community
      health care centers into comprehensive or standard care interventions.
      Comprehensive participants received standard care (stage-matched provider
      counseling and assisted goal setting) plus 12 months of telephone counseling and
      tailored newsletters. Primary outcomes were 6- and 12-month self-reported
      physical activity and dietary fat intake. RESULTS: Comprehensive participants
      were more likely than were standard care participants to decrease total physical
      activity (odds ratio [OR] = 3.13; 95% confidence interval [CI] = 1.18, 8.25) and
      increase leisure-time physical activity (OR = 3.82; 95% CI = 1.41, 10.3) at 6
      months (no 12-month differences). Mean reductions in Dietary Risk Assessment
      score occurred in both groups but were greater among comprehensive participants
      than among standard care participants (6 months, -8.50 vs -5.34; 12 months, -7.16
      vs -3.37; P < .001). CONCLUSIONS: The comprehensive intervention improved women's
      leisure-time physical activity and dietary fat intake, highlighting a replicable
      model to help primary care providers implement lifestyle counseling.

PMID- 21852630
TI  - Low-risk lifestyle behaviors and all-cause mortality: findings from the National
      Health and Nutrition Examination Survey III Mortality Study.
AB  - OBJECTIVES: We examined the relationship between 4 low-risk behaviors-never
      smoked, healthy diet, adequate physical activity, and moderate alcohol
      consumption-and mortality in a representative sample of people in the United
      States. METHODS: We used data from 16958 participants aged 17 years and older in
      the National Health and Nutrition Examination Survey III Mortality Study from
      1988 to 2006. RESULTS: The number of low-risk behaviors was inversely related to
      the risk for mortality. Compared with participants who had no low-risk behaviors,
      those who had all 4 experienced reduced all-cause mortality (adjusted hazard
      ratio [AHR]=0.37; 95% confidence interval [CI]=0.28, 0.49), mortality from
      malignant neoplasms (AHR=0.34; 95% CI=0.20, 0.56), major cardiovascular disease
      (AHR=0.35; 95% CI=0.24, 0.50), and other causes (AHR=0.43; 95% CI=0.25, 0.74).
      The rate advancement periods, representing the equivalent risk from a certain
      number of years of chronological age, for participants who had all 4 high-risk
      behaviors compared with those who had none were 11.1 years for all-cause
      mortality, 14.4 years for malignant neoplasms, 9.9 years for major cardiovascular
      disease, and 10.6 years for other causes. CONCLUSIONS: Low-risk lifestyle factors
      exert a powerful and beneficial effect on mortality.

PMID- 21852631
TI  - A model for dental practice in the 21st century.
AB  - The dental profession is responsible for the prevention, diagnosis, and treatment
      of diseases and disorders of the oral cavity and related structures. Although the
      majority of the US population receives excellent oral health care, a significant
      portion is unable to access regular care. Along with proposals to develop
      midlevel providers, the scope of practice for dentists needs to be
      reconceptualized and expanded. A broad number of primary health care activities
      may be conducted in the dental office, such as screening for hypertension,
      diabetes mellitus, and dermatopathology; smoking prevention and cessation
      activities; and obesity interventions. More than 70% of adults saw a dentist in
      the past year, which represents an unrealized opportunity to improve both oral
      health and general health.

PMID- 21852632
TI  - Alcohol advertising at Boston subway stations: an assessment of exposure by race
      and socioeconomic status.
AB  - OBJECTIVES: We investigated the frequency of alcohol ads at all 113 subway and
      streetcar stations in Boston and the patterns of community exposure stratified by
      race, socioeconomic status, and age. METHODS: We assessed the extent of alcohol
      advertising at each station in May 2009. We measured gross impressions and gross
      rating points (GRPs) for the entire Greater Boston population and for Boston
      public school student commuters. We compared the frequency of alcohol advertising
      between neighborhoods with differing demographics. RESULTS: For the Greater
      Boston population, alcohol advertising at subway stations generated 109 GRPs on a
      typical day. For Boston public school students in grades 5 to 12, alcohol
      advertising at stations generated 134 GRPs. Advertising at stations in low
      poverty neighborhoods generated 14.1 GRPs and at stations in high-poverty areas,
      63.6 GRPs. CONCLUSIONS: Alcohol ads reach the equivalent of every adult in the
      Greater Boston region and the equivalent of every 5th- to 12th-grade public
      school student each day. More alcohol ads were displayed in stations in
      neighborhoods with high poverty rates than in stations in neighborhoods with low
      poverty rates.

PMID- 21852633
TI  - Informational privacy, public health, and state laws.
AB  - Developments in information technology that make it possible to rapidly transmit
      health information also raise questions about the possible inappropriate use and
      protection of identifiable (or potentially identifiable) personal health
      information. Despite efforts to improve state laws, adoption of provisions has
      lagged. We found that half of states have no statutes addressing nondisclosure of
      personally identifiable health information generally held by public health
      agencies. Exceptional treatment of HIV, sexually transmitted infections, or
      tuberculosis-related information was common. Where other provisions were found,
      there was little consistency in the laws across states. The variation in state
      laws supports the need to build consensus on the appropriate use and disclosure
      of public health information among public health practitioners.

PMID- 21852634
TI  - A clinical nurse's perspective of public and community health.

PMID- 21852635
TI  - Aligning community engagement with traditional authority structures in global
      health research: a case study from northern Ghana.
AB  - Despite the recognition of its importance, guidance on community engagement
      practices for researchers remains underdeveloped, and there is little empirical
      evidence of what makes community engagement effective in biomedical research. We
      chose to study the Navrongo Health Research Centre in northern Ghana because of
      its well-established community engagement practices and because of the
      opportunity it afforded to examine community engagement in a traditional African
      setting. Our findings suggest that specific preexisting features of the community
      have greatly facilitated community engagement and that using traditional
      community engagement mechanisms limits the social disruption associated with
      research conducted by outsiders. Finally, even in seemingly ideal, small, and
      homogeneous communities, cultural issues exist, such as gender inequities, that
      may not be effectively addressed by traditional practices alone.

PMID- 21852636
TI  - Health status, neighborhood socioeconomic context, and premature mortality in the
      United States: The National Institutes of Health-AARP Diet and Health Study.
AB  - OBJECTIVES: We examined whether the risk of premature mortality associated with
      living in socioeconomically deprived neighborhoods varies according to the health
      status of individuals. METHODS: Community-dwelling adults (n = 566,402; age = 50
      71 years) in 6 US states and 2 metropolitan areas participated in the ongoing
      prospective National Institutes of Health-AARP Diet and Health Study, which began
      in 1995. We used baseline data for 565,679 participants on health behaviors, self
      rated health status, and medical history, collected by mailed questionnaires.
      Participants were linked to 2000 census data for an index of census tract
      socioeconomic deprivation. The main outcome was all-cause mortality ascertained
      through 2006. RESULTS: In adjusted survival analyses of persons in good-to
      excellent health at baseline, risk of mortality increased with increasing levels
      of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality
      disparities among persons in fair-to-poor health were not statistically
      significant after adjustment for demographic characteristics, educational
      achievement, lifestyle, and medical conditions. CONCLUSIONS: Neighborhood
      socioeconomic inequalities lead to large disparities in risk of premature
      mortality among healthy US adults but not among those in poor health.

PMID- 21852637
TI  - Reinforcement of smoking and drinking: tobacco marketing strategies linked with
      alcohol in the United States.
AB  - OBJECTIVES: We investigated tobacco companies' knowledge about concurrent use of
      tobacco and alcohol, their marketing strategies linking cigarettes with alcohol,
      and the benefits tobacco companies sought from these marketing activities.
      METHODS: We performed systematic searches on previously secret tobacco industry
      documents, and we summarized the themes and contexts of relevant search results.
      RESULTS: Tobacco company research confirmed the association between tobacco use
      and alcohol use. Tobacco companies explored promotional strategies linking
      cigarettes and alcohol, such as jointly sponsoring special events with alcohol
      companies to lower the cost of sponsorships, increase consumer appeal, reinforce
      brand identity, and generate increased cigarette sales. They also pursued
      promotions that tied cigarette sales to alcohol purchases, and cigarette
      promotional events frequently featured alcohol discounts or encouraged alcohol
      use. CONCLUSIONS: Tobacco companies' numerous marketing strategies linking
      cigarettes with alcohol may have reinforced the use of both substances. Because
      using tobacco and alcohol together makes it harder to quit smoking, policies
      prohibiting tobacco sales and promotion in establishments where alcohol is served
      and sold might mitigate this effect. Smoking cessation programs should address
      the effect that alcohol consumption has on tobacco use.

PMID- 21852638
TI  - Seven-year patterns in US cigar use epidemiology among young adults aged 18-25
      years: a focus on race/ethnicity and brand.
AB  - OBJECTIVES: We examined patterns in cigar use among young adults, aged 18-25
      years, focusing on race/ethnicity and brand. METHODS: We conducted a secondary
      data analysis of cross-sectional waves of the National Survey on Drug Use and
      Health, 2002-2008, using multivariate logistic regression to assess time trends
      in past 30 days cigar use, past 30 days use of a "top 5" cigar brand, cigar use
      intensity, and age at first cigar use. RESULTS: Cigar use has increased among
      White non-Hispanic men aged 18 to 25 years, from 12.0% in 2002 to 12.7% in 2008.
      Common predictors of all outcomes included male gender and past 30 days use of
      cigarettes, marijuana, and blunts. Additional predictors of past 30 days cigar
      and "top 5" brand use included younger age, non-Hispanic Black or White race,
      lower income, and highest level of risk behavior. College enrollment predicted
      intensity of use and "top 5" brand use. CONCLUSIONS: Recent legislative
      initiatives have changed how cigars are marketed and may affect consumption.
      National surveys should include measures of cigar brand and little cigar and
      cigarillo use to improve cigar use estimates.

PMID- 21852639
TI  - Secondhand tobacco smoke: a source of lead exposure in US children and
      adolescents.
AB  - OBJECTIVES: We evaluated the relationship between secondhand tobacco smoke (SHS)
      exposure and blood lead levels in US children and adolescents. METHODS: We
      analyzed data from 6830 participants aged 3-19 years in the National Health and
      Nutrition Examination Survey (1999-2004) who were not active smokers and for whom
      SHS exposure information and blood lead measurements were available. RESULTS:
      After multivariable adjustment, participants in the highest quartile of serum
      cotinine (>= 0.44 MUg/L) had 28% (95% confidence interval = 21%, 36%) higher
      blood lead levels than had those in the lowest quartile (< 0.03 MUg/L).
      Similarly, blood lead levels were 14% and 24% higher in children who lived with 1
      or with 2 or more smokers, respectively, than they were in children living with
      no smokers. Among participants for whom lead dust information was available, the
      associations between SHS and blood lead levels were similar before and after
      adjustment for lead dust concentrations. CONCLUSIONS: SHS may contribute to
      increased blood lead levels in US children. Lead dust does not appear to mediate
      this association, suggesting inhalation as a major pathway of exposure.
      Eliminating SHS exposure could reduce lead exposure in children.

PMID- 21852640
TI  - Increasing hookah use in California.
AB  - Hookah use is gaining popularity nationwide. We determined the correlates and
      trends for hookah use from the California Tobacco Survey. Between 2005 and 2008
      hookah use increased more than 40%, and in 2008, 24.5% of young men reported ever
      using a hookah. Hookah use was more common among the young (18-24 years), the
      educated, the non-Hispanic Whites, and the cigarette smokers. Hookah use is
      increasing in California, especially among young adults, and in 2008 reached the
      highest prevalence ever reported for both genders.

PMID- 21852641
TI  - Access to dental care: is there a problem?

PMID- 21852642
TI  - Another look at the human papillomavirus vaccine experience in Canada.
AB  - Policy debates about immunization frequently focus on classic trade-offs between
      individual versus collective well-being. Publicly funded immunization programs
      are usually justified on the basis of widespread public benefit with minimal
      individual risk. We discuss the example of the policy process surrounding the
      adoption of the human papillomavirus (HPV) vaccine in Canada to consider whether
      public good arguments continue to dominate immunization policymaking.
      Specifically, we show how a range of stakeholders framed HPV vaccination as a
      personal-rather than a public-matter, despite the absence of a controversy over
      mandatory immunization as was the case in the United States. Our findings suggest
      an erosion of the persuasiveness of public good arguments around collective
      immunization programs in the policy discourse.

PMID- 21852643
TI  - Residential carbon monoxide detector failure rates in the United States.
AB  - There are more than 38 million residential carbon monoxide detectors installed in
      the United States. We tested 30 detectors in use and found that more than half
      failed to function properly, alarming too early or too late. Forty percent of
      detectors failed to alarm in hazardous concentrations, despite outward
      indications that they were operating as intended. Public health professionals
      should consider community education concerning detector use and should work with
      stakeholders to improve the reliability and accuracy of these devices.

PMID- 21852644
TI  - Changes in retail tobacco promotions in a cohort of stores before, during, and
      after a tobacco product display ban.
AB  - We used a longitudinal design to investigate the impact of a government policy
      banning the display of tobacco products at the point of sale. The extent of
      tobacco promotions in 481 randomly selected stores was documented at 4 points in
      time (2005-2009). Tobacco promotions were greatly reduced after implementation of
      the display ban. A ban on the display of tobacco products and other signage and
      promotions at retail is a critical tobacco-control policy to reduce people's
      exposure to tobacco marketing.

PMID- 21852645
TI  - Lee K. Frankel (1867-1931): public health leader and life insurance executive.

PMID- 21852646
TI  - Intergenerational relationships between the smoking patterns of a population
      representative sample of US mothers and the smoking trajectories of their
      children.
AB  - OBJECTIVES: We assessed intergenerational transmission of smoking in mother-child
      dyads. METHODS: We identified classes of youth smoking trajectories using mixture
      latent trajectory analyses with data from the Children and Young Adults of the
      National Longitudinal Survey of Youth (n = 6349). We regressed class membership
      on prenatal and postnatal exposure to maternal smoking, including social and
      behavioral variables, to control for selection. RESULTS: Youth smoking
      trajectories entailed early-onset persistent smoking, early-onset experimental
      discontinued smoking, late-onset persistent smoking, and nonsmoking. The
      likelihood of early onset versus late onset and early onset versus nonsmoking
      were significantly higher among youths exposed prenatally and postnatally versus
      either postnatally alone or unexposed. Controlling for selection, the increased
      likelihood of early onset versus nonsmoking remained significant for each
      exposure group versus unexposed, as did early onset versus late onset and late
      onset versus nonsmoking for youths exposed prenatally and postnatally versus
      unexposed. Experimental smoking was notable among youths whose mothers smoked but
      quit before the child's birth. CONCLUSIONS: Both physiological and social role
      modeling mechanisms of intergenerational transmission are evident. Prioritization
      of tobacco control for pregnant women, mothers, and youths remains a critical,
      interrelated objective.

PMID- 21852647
TI  - Relations of meeting national public health recommendations for muscular
      strengthening activities with strength, body composition, and obesity: the
      Women's Injury Study.
AB  - OBJECTIVES: We examined the relations of meeting or not meeting the 2008 Physical
      Activity Guidelines for Americans recommendations for muscular strengthening
      activities with percentage of body fat, body mass index (BMI; defined as weight
      in kilograms divided by height in meters, squared), muscular strength, and
      obesity classification in women. METHODS: We analyzed data on 918 women aged 20
      to 83 years in the Women's Injury Study from 2007 to 2009. A baseline orthopedic
      examination included measurement of height, body weight, skinfolds, and muscle
      strength. RESULTS: Women who met muscle strengthening activity recommendations
      had significantly lower BMI and percentage of body fat and higher muscle
      strength. Women not meeting those recommendations were more likely to be obese
      (BMI >= 30) compared with women who met the recommendations after we adjusted for
      age, race, and aerobic physical activity (odds ratio = 2.28; 95% confidence
      interval = 1.61, 3.23). CONCLUSIONS: There was a small but significant positive
      association between meeting muscle strengthening activity recommendations and
      muscular strength, a moderate inverse association with body fat percentage, and a
      strong inverse association with obesity classification, providing preliminary
      support for the muscle strengthening activity recommendation for women.

PMID- 21852648
TI  - The dental profession in transition.

PMID- 21852649
TI  - Public health support for the health home model.

PMID- 21852650
TI  - Differences in the social networks of African American men who have sex with men
      only and those who have sex with men and women.
AB  - OBJECTIVES: We compared social network characteristics of African American men
      who have sex with men only (MSMO) with social network characteristics of African
      American men who have sex with men and women (MSMW). METHODS: Study participants
      were 234 African American men who have sex with men who completed a baseline
      social network assessment for a pilot behavioral HIV prevention intervention in
      Baltimore, Maryland, from 2006 through 2009. We surveyed the men to elicit the
      characteristics of their social networks, and we used logistic regression models
      to assess differences in network characteristics. RESULTS: MSMO were
      significantly more likely than were MSMW to be HIV-positive (52% vs 31%). We
      found no differences between MSMO and MSMW in the size of kin networks or
      emotional and material support networks. MSMW had denser sexual networks,
      reported more concurrent and exchange partners, used condoms with more sexual
      partners, and reported interaction with a larger number of sexual partners at
      least once a week. CONCLUSIONS: Although there were many similarities in the
      social and sexual network characteristics of MSMO and MSMW, differences did
      exist. HIV prevention interventions should address the unique needs of African
      American MSMW.

PMID- 21852651
TI  - Trends in smoking among adults from 1980 to 2009: the Minnesota heart survey.
AB  - OBJECTIVES: We examined population-based smoking trends in Minnesota between 1980
      and 2009. METHODS: The Minnesota Heart Survey (MHS) is a population-based,
      serial, cross-sectional study of cardiovascular risk factor trends among
      Minneapolis-Saint Paul metropolitan residents. The MHS recently completed its
      sixth survey (1980-1982 [n = 3799], 1985-1987 [n = 4641], 1990-1992 [n = 5159],
      1995-1997 [n = 6690], 2000-2002 [n = 3281], and 2007-2009 [n = 3179]). We used
      MHS data to examine smoking trends among adults aged 25 to 74 years by means of
      age-adjusted generalized linear mixed models. RESULTS: Between 1980 and 2009, the
      prevalence of current smoking decreased from 32.8% to 15.5% for men and from
      32.7% to 12.2% for women (P < .001 for each). Greater decreases occurred among
      those with higher income and those with more education. Among currently smoking
      men, the number of cigarettes smoked per day decreased from 26.0 in the 1980-1982
      survey to 16.0 in the 2007-2009 survey (P < .001). Similar trends were observed
      among women. CONCLUSIONS: Although the prevalence of smoking and cigarette
      consumption decreased from the 1980-1982 period to the 2007-2009 period,
      interventions specifically designed for those of lower socioeconomic status are
      needed.

PMID- 21852652
TI  - Quid pro quo: tobacco companies and the black press.
AB  - OBJECTIVES: We explored the relationship between tobacco companies and the Black
      press, which plays an important role in conveying information and opinions to
      Black communities. METHODS: In this archival case study, we analyzed data from
      internal tobacco industry documents and archives of the National Newspaper
      Publishers Association (NNPA), the trade association of the Black press. RESULTS:
      In exchange for advertising dollars and other support, the tobacco industry
      expected and received support from Black newspapers for tobacco industry policy
      positions. Beginning in the 1990s, resistance from within the Black community and
      reduced advertising budgets created counterpressures. The tobacco industry,
      however, continued to sustain NNPA support. CONCLUSIONS: The quid pro quo between
      tobacco companies and the Black press violated journalistic standards and
      represented an unequal trade. Although numerous factors explain today's tobacco
      related health disparities, the Black press's service to tobacco companies is
      problematic because of the trust that the community placed in such media.
      Understanding the relationship between the tobacco industry and the NNPA provides
      insight into strategies that the tobacco industry may use in other communities
      and countries.

PMID- 21852653
TI  - The wrong tool for the job: diabetes public health programs and practice
      guidelines.
AB  - We surveyed state diabetes programs to determine whether they develop and
      disseminate diabetes guidelines. We found they largely disseminate clinical
      practice guidelines developed from subspecialty organizations, do not prioritize
      among the many recommendations contained in diabetes guidelines, and have not
      adapted guidelines to focus on population rather than individual health. An
      opportunity exists for state diabetes control programs to better align guidelines
      with public health goals.

PMID- 21852654
TI  - Rethinking Dr. Spock.

PMID- 21852656
TI  - The influence of changes in dental care coverage on dental care utilization among
      retirees and near-retirees in the United States, 2004-2006.
AB  - OBJECTIVES: We examined dental care utilization transition dynamics between 2004
      and 2006 in the context of changing dental coverage status. METHODS: We used data
      from the Health and Retirement Study for persons aged 51 years and older to
      estimate a multivariable model of dental care use transitions with controls for
      dental coverage and retirement transitions and other potentially confounding
      covariates. RESULTS: We found that Americans aged 51 years and older who lost
      dental coverage between the 2004 and 2006 survey periods were more likely to stop
      dental care use between periods, and those who gained coverage were more likely
      to start dental care use between periods, than those without coverage in both
      periods. CONCLUSIONS: Dental coverage transitions and status have a strong effect
      on transitions in dental care use. Given that retirement is a time when many
      experience a loss of dental coverage, older adults may be at risk for sporadic
      dental care and even stopping use, leading to worse dental and potentially
      overall health.

PMID- 21852657
TI  - Estimates of smoking-related property costs in California multiunit housing.
AB  - We systematically evaluated smoking-related costs in multiunit housing. From 2008
      to 2009, we surveyed California multiunit housing owners or managers on their
      past-year smoking-related costs and smoke-free policies. A total of 27.1% of
      respondents had incurred smoking-related costs (mean $4935), and 33.5% reported
      complete smoke-free policies, which lowered the likelihood of incurring smoking
      related costs. Implementing statewide complete smoke-free policies may save
      multiunit housing property owners $ 18,094,254 annually.

PMID- 21852655
TI  - Causes of the decline in cigarette smoking among African American youths from the
      1970s to the 1990s.
AB  - Adult cigarette smoking prevalence trends among African Americans (AAs) and
      Whites are similar. However, during the decline in youth smoking that occurred
      between the mid-1970s and the early 1990s, the drop in smoking rates among AA
      adolescents was more than double that among Whites. We examined the evidence for
      potential explanations for this phenomenon. On the basis of our findings, we
      propose that racial differences in parental attitudes, religious ties, negative
      perceptions and experiences of the health effects of smoking, worsening poverty,
      increased use of food stamps, and price sensitivity were major factors
      contributing to the more rapid decrease in and continued lower rates of smoking
      among AA youths.

PMID- 21852658
TI  - Racial/Ethnic disparities in mortality risk among US veterans with traumatic
      brain injury.
AB  - OBJECTIVES: We examined the association of race/ethnicity with mortality risk in
      a national cohort of US veterans clinically diagnosed with traumatic brain
      injury. METHODS: Between January 1, 2006 and December 31, 2006, we obtained data
      from a national cohort study of 7885 non-Hispanic White, 1748 Non-Hispanic Black,
      314 Hispanic, and 4743 other or missing race/ethnicity veterans clinically
      diagnosed with traumatic brain injury in Veterans Affairs medical centers and
      community-based outpatient clinics. RESULTS: Overall mortality at 48 months was
      6.7% in Hispanic, 2.9% in non-Hispanic White, and 2.7% in non-Hispanic Black
      veterans. Compared with non-Hispanic White, Hispanic ethnicity was positively
      associated with a higher mortality risk (hazard ratio [HR] = 2.33; 95% confidence
      interval [CI] = 1.49, 3.64) in the race/ethnicity-only adjusted model. After
      adjusting for sociodemographic characteristics and comorbidities, Hispanic
      ethnicity continued to be positively associated (HR = 1.61; 95% CI = 1.00, 2.58)
      with a higher mortality risk relative to non-Hispanic White ethnicity.
      CONCLUSIONS: Hispanic ethnicity is positively associated with higher mortality
      risk among veterans clinically diagnosed with traumatic brain injury. More
      research is needed to understand the reasons for this disparity.

PMID- 21852659
TI  - Effectiveness and spillover of an after-school health promotion program for
      Hispanic elementary school children.
AB  - OBJECTIVES: We evaluated the effectiveness and spillover of an after-school
      health education and physical activity program among Hispanic elementary school
      children. METHODS: In fall 2008, students in third through fifth grades in 6
      schools in El Paso, Texas (n = 901), were randomized to intervention (n = 292
      participants) or control (n = 354) classrooms (4 unknown). Intervention
      classrooms also contained a spillover group (n = 251) that did not join the after
      school program but that completed measurements and surveys. The intervention was
      a 12-week culturally tailored after-school program meeting twice a week. Four
      month outcomes were body mass index, aerobic capacity, and dietary intentions and
      knowledge. We calculated intervention exposure as the proportion of after-school
      participants per classroom. RESULTS: Intervention exposure predicted lower body
      mass index (P = .045), higher aerobic capacity (P = .012), and greater intentions
      to eat healthy (P = .046) for the classroom at follow-up. Intervention
      effectiveness increased with increasing proportions of intervention participants
      in a classroom. Nonparticipants who had classroom contact with program
      participants experienced health improvements that could reduce their risk of
      obesity. CONCLUSIONS: Spillover of beneficial intervention effects to
      nonparticipants is a valuable public health benefit and should be part of program
      impact assessments.

PMID- 21852660
TI  - Personal disaster preparedness of dialysis patients in North Carolina.
AB  - BACKGROUND AND OBJECTIVES: Dialysis patients are among the most vulnerable
      patients during a disaster because they are sensitive to a lapse in treatment.
      Although thorough preparation could mitigate disaster effects, we hypothesized
      that dialysis patients' personal and medical disaster preparedness was
      inadequate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prevalence study
      surveyed mentally competent adults requiring care at six regional dialysis
      centers. We asked questions regarding demographics, general disaster preparedness
      utilizing Homeland Security recommended item lists, dialysis-specific preparation
      for an individual to shelter in place, and preparatory steps for a forced
      evacuation. To determine if preparedness differed by demographic variables
      (gender, race, age, and education) chi-squared tests were used. RESULTS: Four
      hundred forty-two patients were approached, and 311 (70%) completed the survey.
      Participants were 54% male, 60% black, average age was 58 (+/- 15) years, and
      although 79% completed high school, 50% of our sample had marginal or low health
      literacy. Although all units had a disaster preparedness program in place, the
      general disaster preparedness of most participants was poor. Age, gender, race,
      education, literacy, and socioeconomic status did not affect general disaster
      preparedness. However, home peritoneal dialysis patients were significantly more
      likely to be prepared for a disaster compared with hemodialysis patients. No
      other significant associations were noted. CONCLUSIONS: Irrespective of
      sociodemographic characteristics, most subjects were unprepared for a disaster.
      Dialysis patients were poorly prepared to shelter in place or to evacuate in the
      face of a disaster. Education regarding personal and dialysis-specific disaster
      preparedness is warranted.

PMID- 21852661
TI  - Efficacy of influenza A H1N1/2009 vaccine in hemodialysis and kidney transplant
      patients.
AB  - BACKGROUND AND OBJECTIVES: Data are needed to assess safety and efficacy of the
      2009 pandemic influenza A H1N1 vaccine in renal patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We prospectively evaluated seroconversion,
      predictors of response, and vaccine safety in renal patients. Hemagglutination
      inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus
      were performed in 79 transplant patients, 48 hemodialysis patients, and 15
      healthy workers before and 1 month after vaccination. Healthy controls and 88 of
      127 renal patients were vaccinated. Seroconversion was defined as at least 2
      dilutions increase in titer. RESULTS: We excluded 19 individuals seroprotected
      (>=1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96
      vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27
      nonvaccinated patients, P = 0.007). For vaccinated subgroups, efficacy was 41.8%
      in transplant patients (P = 0.039 versus nonvaccinated), 33.3% in hemodialysis
      patients (P = 0.450), and 81.8% in controls. Healthy controls showed better
      response to vaccine than transplant (P = 0.021) and dialysis (P = 0.012)
      patients. For the transplant subgroup, longer time after transplantation (P =
      0.028) was associated with seroconversion, but no influence was found for age,
      gender, renal function, or immunosuppression. In the hemodialysis subgroup,
      younger age was associated with response (55.7 +/- 20.8 versus 71.6 +/- 10.1
      years, P = 0.042), but other specific variables, including Kt/V or time on
      dialysis, were not. No serious adverse events were reported, and kidney function
      was stable. CONCLUSION: The novel influenza A 2009 H1N1 vaccine was safe in renal
      patients, although administration of a single dose of adjuvanted vaccine induced
      a poor response in these patients.

PMID- 21852662
TI  - The impact of antihypertensive drug therapy on endotoxemia in elderly patients
      with chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Endotoxin (ET) is recognized to cause adverse effects
      on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET
      is described in heart failure. Chronic kidney disease (CKD) is common in older
      people and aggressive BP control is the cornerstone of management. We therefore
      studied ET after improvement of the overall CV milieu with introduction of
      optimized antihypertensive therapy (AHT). DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We recruited 40 hypertensive nondiabetic patients (>=70 years) with
      CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was
      performed after complete AHT washout and repeated after AHT reintroduction to
      target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by
      applanation tonometry, central hemodynamics by continuous digital pulse wave
      analysis, vascular calcification (VC) by superficial femoral artery CT, and serum
      ET by Limulus Amebocyte assay. RESULTS: Mean age was 76 +/- 5 years, estimated
      GFR (eGFR) (CKD group) was 40 +/- 14 ml/min per 1.73 m(2), and achieved BP was
      128/69 mmHg. Washout ET was 0.042 +/- 0.011 EU/ml and was independent of renal
      function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C
      reactive protein. ET significantly decreased with AHT (to 0.020 +/- 0.028 EU/ml;
      P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave
      reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic
      vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC,
      PWV, gender, age, BP, or high-sensitivity C-reactive protein. CONCLUSIONS:
      Elderly patients with hypertension have elevated serum ET. Improvement of their
      CV status with optimized AHT is associated with a significant reduction in
      endotoxemia. Further investigation of the potential pathophysiological mechanisms
      linking CV disease and CKD with this previously unappreciated effect of AHT
      appears warranted.

PMID- 21852663
TI  - The patient as a limit to dialysis technology.

PMID- 21852664
TI  - Metabolic syndrome and kidney disease: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Observational studies have reported an association
      between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic
      kidney disease (CKD) with varying risk estimates. We aimed to systematically
      review the association between MetS, its components, and development of
      microalbuminuria or proteinuria and CKD. DESIGN, SETTING, PARTICIPANTS AND
      MEASUREMENTS AND POPULATION: We searched MEDLINE (1966 to October 2010), SCOPUS,
      and the Web of Science for prospective cohort confidence interval (CI) studies
      that reported the development of microalbuminuria or proteinuria and/or CKD in
      participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m(2) were
      extracted from individual studies and pooled using a random effects model. The
      results for proteinuria outcomes were not pooled because of the small number of
      studies. RESULTS: Eleven studies (n = 30,146) were included. MetS was
      significantly associated with the development of eGFR <60 ml/min per 1.73 m(2)
      (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed
      to increase as the number of components of MetS increased (trend P value = 0.02).
      In patients with MetS, the odds ratios (95% CI) for development of eGFR <60
      ml/min per 1.73 m(2) for individual components of MetS were: elevated blood
      pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL
      cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired
      fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for
      development of microalbuminuria or overt proteinuria with MetS. CONCLUSIONS: MetS
      and its components are associated with the development of eGFR <60 ml/min per
      1.73 m(2) and microalbuminuria or overt proteinuria.

PMID- 21852665
TI  - Attending rounds: a patient with drug-resistant hypertension.
AB  - Drug-resistant hypertension is present in about one in eight patients with high
      BP. It can be a frustrating and expensive condition to pursue from an office
      based perspective. In this review, utilizing the American Heart Association
      scientific statement on drug-resistant hypertension as a guide, a case of drug
      resistant hypertension is presented and walked through exactly as encountered by
      the author. Woven into the discussion is a combination of insights from the
      literature on this topic, blended with the experience of the author. This is not
      intended as an exhaustive review of each step in the evaluation and management
      process but, rather, as an overview incorporating a few carefully chosen
      references and, hopefully, a logical and useful approach to a common clinical
      challenge.

PMID- 21852666
TI  - Vaccinations in kidney transplant patients: searching for optimal protection.

PMID- 21852667
TI  - IL-6 levels, nutritional status, and mortality in prevalent hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: The influence of serum IL-6 levels on nutritional
      status in chronic hemodialysis (HD) patients remains to be elucidated. The
      present report describes a prospective longitudinal study of IL-6 levels and
      nutritional parameters to determine whether high IL-6 levels are independently
      associated with nutritional status over time in a cohort of prevalent
      hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 85
      clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 +/
      10.6 years, were studied after exclusion of patients with BMI < 20 kg/m(2)
      and/or serum albumin <35 g/L. IL-6, dietary energy and protein intake, and
      biochemical markers of nutrition and body composition (anthropometry and
      bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months
      following enrollment. Observation of this cohort was continued over 2 additional
      years. RESULTS: IL-6 levels increased with time in both unadjusted (linear
      estimate: 2.57 +/- 0.44 pg/ml per 2 yrs; P = 0.001) and adjusted models (linear
      estimate: 2.35 +/- 0.57 pg/ml per 2 yrs; P = 0.049). Significant reductions of
      daily energy intake, laboratory markers (albumin, transferrin, cholesterol,
      creatinine), and body composition (fat mass) with higher IL-6 levels were
      observed over the duration of the longitudinal observation period. However, none
      of the studied parameters were associated with changes in IL-6 levels over time
      (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of
      survival were correlated with the baseline serum IL-6 levels (P = 0.004 by log
      rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for
      death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for
      demographic and clinical parameters. CONCLUSIONS: Our results suggest that higher
      serum IL-6 levels are associated with all-cause mortality without additional
      changes in clinical and laboratory markers of nutritional status in clinically
      stable HD patients.

PMID- 21852668
TI  - Assessing glomerular filtration rate in hospitalized patients: a comparison
      between CKD-EPI and four cystatin C-based equations.
AB  - BACKGROUND AND OBJECTIVES: A specific method is required for estimating
      glomerular filtration rate GFR in hospitalized patients. Our objective was to
      validate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
      and four cystatin C (CysC)-based equations in this setting. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This was an epidemiologic, cross-sectional study in
      a random sample of hospitalized patients (n = 3114). We studied the accuracy of
      the CKD-EPI and four CysC-based equations--based on (1) CysC alone or (2)
      adjusted by gender; (3) age, gender, and race; and (4) age, gender, race, and
      creatinine, respectively--compared with GFR measured by iohexol clearance (mGFR).
      Clinical, biochemical, and nutritional data were also collected. RESULTS: The
      CysC equation 3 significantly overestimated the GFR (bias of 7.4 ml/min per 1.73
      m(2)). Most of the error in creatinine-based equations was attributable to
      calculated muscle mass, which depended on patient's nutritional status. In
      patients without malnutrition or reduced body surface area, the CKD-EPI equation
      adequately estimated GFR. Equations based on CysC gave more precise mGFR
      estimates when malnutrition, extensive reduction of body surface area, or loss of
      muscle mass were present (biases of 1 and 1.3 ml/min per 1.73 m(2) for equations
      2 and 4, respectively, versus 5.9 ml/min per 1.73 m(2) for CKD-EPI). CONCLUSIONS:
      These results suggest that the use of equations based on CysC and gender, or
      CysC, age, gender, and race, is more appropriate in hospitalized patients to
      estimate GFR, since these equations are much less dependent on patient's
      nutritional status or muscle mass than the CKD-EPI equation.

PMID- 21852669
TI  - Hemodynamic correlates of proteinuria in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Brachial artery measures of BP are associated with
      increasing degrees of proteinuria. Whether central measures of BP or vascular
      stiffness are associated with increased risk of proteinuria in patients with
      chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Measurements of central and brachial artery BP, and aortic pulse
      wave velocity (PWV) were performed in a cross-sectional cohort of patients with
      CKD (n = 2144) from the Chronic Renal Insufficiency Cohort (CRIC) study to
      determine factors which predict increased risk of proteinuria. Multivariate
      analysis stratified by diabetes included age, ethnicity, gender, estimated
      glomerular filtration rate (GFR), waistline, smoking, heart rate, and medications
      to evaluate the relationship of hemodynamic factors and proteinuria. RESULTS:
      Brachial artery systolic BP (SBP) was important as an explanatory factor for
      variations in proteinuria among both diabetics (R(2) = 0.40, P < 0.0001) and non
      diabetics (R(2) = 0.38, P < 0.001). Measures of peripheral pulse pressure (PP),
      central SBP, and central pulse pressure added little to the explained variation
      in proteinuria beyond brachial artery SBP, whereas PWV as a measure of vascular
      stiffness incrementally accounted for a significant portion of variation in
      proteinuria beyond that explained by brachial artery SBP in diabetics (R(2) =
      0.42, P < 0.001) but not non diabetics. CONCLUSIONS: Brachial artery SBP and PWV
      are both associated with variations in proteinuria in patients with CKD.

PMID- 21852670
TI  - Management of acute kidney injury: it's the squeaky wheel that gets the oil!

PMID- 21852671
TI  - Albuminuria and estimated glomerular filtration rate as predictors of diabetic
      end-stage renal disease and death.
AB  - BACKGROUND AND OBJECTIVES: We investigated predictive value of albuminuria and
      estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes. DESIGN,
      SETTING, PARTICIPANTS AND MEASUREMENTS: Beginning in 1982, 2420 diabetic Pima
      Indians >=18 years old were followed until they developed ESRD or died or until
      December 31, 2005. Individuals were classified at baseline by urinary albumin-to
      creatinine ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease
      Epidemiology Collaboration equation. Predictors of ESRD and mortality were
      examined by proportional hazards regression. RESULTS: During a mean follow-up of
      10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals
      with macroalbuminuria (ACR >= 300 mg/g) was 9.3 times that of those with
      normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of
      diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m(2) was
      81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m(2). Models that
      combined albuminuria and eGFR added significant predictive information about risk
      of ESRD or death compared with models containing eGFR or albuminuria alone. The
      hazard ratio for ESRD associated with a 10-ml/min per 1.73 m(2) lower eGFR was
      1.36, whereas that associated with an increase in albuminuria category was 2.69;
      corresponding hazard ratios for death were 1.15 and 1.37. CONCLUSIONS: These
      results suggest that incorporation of quantitative information about albuminuria
      into staging systems based on eGFR adds significant prognostic information about
      risk for diabetic ESRD and death.

PMID- 21852672
TI  - Pathologic predictors of renal outcome and therapeutic efficacy in IgA
      nephropathy: validation of the oxford classification.
AB  - BACKGROUND AND OBJECTIVES: The Oxford classification of IgA nephropathy (IgAN)
      may aid in predicting prognosis and providing therapeutic strategy but must be
      validated in different ancestry. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      total of 410 patients with IgAN, enrolled from one of the largest renal centers
      in China, were evaluated for the predictive value of the Oxford classification to
      prognosis defined as end stage renal disease. A total of 294 of these patients
      were prospectively treated with renin-angiotensin system blockade and
      immunosuppressants sequentially and were evaluated separately to assess the
      predictive value to therapeutic efficacy (defined as time-averaged proteinuria <1
      g/d). Three pathologists reviewed specimens independently according to the Oxford
      classification and were blinded to clinical data. RESULTS: Segmental
      glomerulosclerosis and tubular atrophy and interstitial fibrosis were independent
      predictive factors of end stage renal disease. Patients who had >25% of glomeruli
      with endocapillary hypercellularity showed higher proteinuria, lower estimated
      GFR, and higher mean BP than patients with less endocapillary hypercellularity.
      Immunosuppressive therapy showed a protective effect to prognosis of
      endocapillary hypercellularity in patients with endoncapillary hypercellularity
      could benefit from immunosuppressive therapy. Mesangial hypercellularity and
      tubular atrophy and interstitial fibrosis were independent factors of
      inefficiency of renin-angiotensin system blockade alone. Crescents were not
      significant in predicting prognosis or in therapeutic efficacy. CONCLUSIONS: The
      Oxford classification may aid in predicting prognosis and providing a therapeutic
      strategy in Chinese patients with IgAN.

PMID- 21852673
TI  - GLUT2 accumulation in enterocyte apical and intracellular membranes: a study in
      morbidly obese human subjects and ob/ob and high fat-fed mice.
AB  - OBJECTIVE: In healthy rodents, intestinal sugar absorption in response to sugar
      rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss
      of insulin action maintains apical GLUT2 location. In human enterocytes, apical
      GLUT2 location has not been reported but may be revealed under conditions of
      insulin resistance. RESEARCH DESIGN AND METHODS: Subcellular location of GLUT2 in
      jejunal enterocytes was analyzed by confocal and electron microscopy imaging and
      Western blot in 62 well-phenotyped morbidly obese subjects and 7 lean human
      subjects. GLUT2 locations were assayed in ob/ob and ob/+ mice receiving oral
      metformin or in high-fat low-carbohydrate diet-fed C57Bl/6 mice. Glucose
      absorption and secretion were respectively estimated by oral glucose tolerance
      test and secretion of [U-(14)C]-3-O-methyl glucose into lumen. RESULTS: In human
      enterocytes, GLUT2 was consistently located in basolateral membranes. Apical
      GLUT2 location was absent in lean subjects but was observed in 76% of obese
      subjects and correlated with insulin resistance and glycemia. In addition,
      intracellular accumulation of GLUT2 with early endosome antigen 1 (EEA1) was
      associated with reduced MGAT4a activity (glycosylation) in 39% of obese subjects
      on a low-carbohydrate/high-fat diet. Mice on a low-carbohydrate/high-fat diet for
      12 months also exhibited endosomal GLUT2 accumulation and reduced glucose
      absorption. In ob/ob mice, metformin promoted apical GLUT2 and improved glucose
      homeostasis. Apical GLUT2 in fasting hyperglycemic ob/ob mice tripled glucose
      release into intestinal lumen. CONCLUSIONS: In morbidly obese insulin-resistant
      subjects, GLUT2 was accumulated in apical and/or endosomal membranes of
      enterocytes. Functionally, apical GLUT2 favored and endosomal GLUT2 reduced
      glucose transepithelial exchanges. Thus, altered GLUT2 locations in enterocytes
      are a sign of intestinal adaptations to human metabolic pathology.

PMID- 21852674
TI  - Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice.
AB  - OBJECTIVE: Obesity is characterized by chronic oxidative stress. Fibroblast
      growth factor 21 (FGF21) has recently been identified as a novel hormone that
      regulates metabolism. NFE2-related factor 2 (Nrf2) is a transcription factor that
      orchestrates the expression of a battery of antioxidant and detoxification genes
      under both basal and stress conditions. The current study investigated the role
      of Nrf2 in a mouse model of long-term high-fat diet (HFD)-induced obesity and
      characterized its crosstalk to FGF21 in this process. RESEARCH DESIGN AND
      METHODS: Wild-type (WT) and Nrf2 knockout (Nrf2-KO) mice were fed an HFD for 180
      days. During this period, food consumption and body weights were measured.
      Glucose metabolism was assessed by an intraperitoneal glucose tolerance test and
      intraperitoneal insulin tolerance test. Total RNA was prepared from liver and
      adipose tissue and was used for quantitative real-time RT-PCR. Fasting plasma was
      collected and analyzed for blood chemistries. The ST-2 cell line was used for
      transfection studies. RESULTS: Nrf2-KO mice were partially protected from HFD
      induced obesity and developed a less insulin-resistant phenotype. Importantly,
      Nrf2-KO mice had higher plasma FGF21 levels and higher FGF21 mRNA levels in liver
      and white adipose tissue than WT mice. Thus, the altered metabolic phenotype of
      Nrf2-KO mice under HFD was associated with higher expression and abundance of
      FGF21. Consistently, the overexpression of Nrf2 in ST-2 cells resulted in
      decreased FGF21 mRNA levels as well as in suppressed activity of a FGF21 promoter
      luciferase reporter. CONCLUSIONS: The identification of Nrf2 as a novel regulator
      of FGF21 expands our understanding of the crosstalk between metabolism and stress
      defense.

PMID- 21852675
TI  - Dysregulation of placental endothelial lipase in obese women with gestational
      diabetes mellitus.
AB  - OBJECTIVE: This study addressed the hypothesis that placental endothelial lipase
      (EL) expression is affected by pregnancies complicated by obesity and gestational
      diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: EL expression in placental
      tissues from pregnancies complicated by obesity, GDM, or obesity combined with
      GDM (obese-GDM) was analyzed by quantitative RT-PCR. Moreover, primary placental
      cells were isolated and treated with insulin, glucose, leptin, or tumor necrosis
      factor (TNF)-alpha, and EL expression was measured. Inhibitors of nuclear factor
      (NF)-kappaB or mitogen-activated protein kinase (MAPK) signaling were used to
      detect potential pathways of EL regulation in primary placental endothelial cells
      (ECs). RESULTS: In placentas from obese-GDM pregnancies, EL expression was
      upregulated by 1.9-fold (P < 0.05) compared with lean pregnancies, whereas
      obesity or GDM alone had no significant effect. Analyses of metabolic parameters
      in maternal venous and umbilical venous plasma revealed significantly increased
      insulin and leptin as well as slightly increased glucose and TNF-alpha values in
      the obese and obese-GDM groups. Cell culture experiments identified TNF-alpha and
      leptin, but not glucose or insulin, as regulators of EL expression in ECs.
      Induction of EL expression by these mediators occurred in a para/endocrine
      manner, since only leptin and TNF-alpha receptors, but not the cytokines
      themselves, were expressed in ECs. Inhibitor experiments suggested that TNF-alpha
      and leptin-mediated upregulation of EL may occur via two different routes.
      Whereas TNF-alpha induced EL upregulation in ECs by activation of the NF-kappaB
      pathway, leptin did not stimulate NF-kappaB or MAPK signaling pathways in these
      cells. CONCLUSIONS: Metabolic inflammation with high leptin and locally increased
      TNF-alpha concentrations at the fetal-placental interface regulates placental EL
      expression.

PMID- 21852676
TI  - Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2
      diabetes.
AB  - OBJECTIVE: In mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL
      function, prevents diabetes-induced atherosclerosis. We sought to determine
      whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F
      treatment improves HDL function in T2D patient plasma in vitro. RESEARCH DESIGN
      AND METHODS: HDL anti-inflammatory function was determined in 93 T2D patients and
      31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte
      chemotactic activity in human aortic endothelial cell monolayers. The HDL
      antioxidant properties were measured using a cell-free assay that uses
      dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by
      liquid chromatography-tandem mass spectrometry. In subgroups of patients and
      control subjects, the HDL inflammatory index was repeated after incubation with L
      4F. RESULTS: The HDL inflammatory index was 1.42 +/- 0.29 in T2D patients and
      0.70 +/- 0.19 in control subjects (P < 0.001). The cell-free assay was impaired
      in T2D patients compared with control subjects (2.03 +/- 1.35 vs. 1.60 +/- 0.80,
      P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was
      higher in T2D patients (1,708 +/- 739 vs. 1,233 +/- 601 relative fluorescence
      units, P < 0.001). All measured oxidized fatty acids were significantly higher in
      the HDLs of T2D patients. There was a significant correlation between the cell
      free assay values and the content of oxidized fatty acids in HDL fractions. L-4F
      treatment restored the HDL inflammatory index in diabetic plasma samples (from
      1.26 +/- 0.17 to 0.71 +/- 0.11, P < 0.001) and marginally affected it in healthy
      subjects (from 0.81 +/- 0.16 to 0.66 +/- 0.10, P < 0.05). CONCLUSIONS: In
      patients with T2D, the content of oxidized fatty acids is increased and the anti
      inflammatory and antioxidant activities of HDLs are impaired.

PMID- 21852677
TI  - Prevalence and characteristics of painful diabetic neuropathy in a large
      community-based diabetic population in the U.K.
AB  - OBJECTIVE: To assess, in the general diabetic population, 1) the prevalence of
      painful neuropathic symptoms; 2) the relationship between symptoms and clinical
      severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in
      painful neuropathy. RESEARCH DESIGN AND METHODS: Observational study of a large
      cohort of diabetic patients receiving community-based health care in northwest
      England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using
      neuropathy symptom score (NSS) and neuropathy disability score (NDS). RESULTS:
      Prevalence of painful symptoms (NSS >=5) and PDN (NSS >=5 and NDS >=3) was 34 and
      21%, respectively. Painful symptoms occurred in 26% of patients without
      neuropathy (NDS <=2) and 60% of patients with severe neuropathy (NDS >8).
      Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that
      of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7-2.4], P < 0.001) and not
      affected by severity of neuropathy, insulin use, foot deformities, smoking, or
      alcohol. Women had 50% increased adjusted risk of painful symptoms compared with
      men (OR = 1.5 [1.4-1.6], P < 0.0001). Despite less neuropathy in South Asians
      (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful
      symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South
      Asians without neuropathy maintained a 50% increased risk of painful neuropathy
      symptoms compared with other ethnic groups (P < 0.0001). CONCLUSIONS: One-third
      of all community-based diabetic patients have painful neuropathy symptoms,
      regardless of their neuropathic deficit. PDN was more prevalent in patients with
      type 2 diabetes, women, and people of South Asian origin. This highlights a
      significant morbidity due to painful neuropathy and identifies key groups who
      warrant screening for PDN.

PMID- 21852678
TI  - Does blood glucose monitoring increase prior to clinic visits in children with
      type 1 diabetes?
AB  - OBJECTIVE: To assess the occurrence of white coat adherence in families with
      children who have type 1 diabetes. RESEARCH DESIGN AND METHODS: Blood glucose
      data were downloaded from meters of 72 children, aged 2-11 years, with type 1
      diabetes at four consecutive clinic visits. Generalized estimating equations were
      used to analyze patterns of blood glucose monitoring (BGM) during the 28 days
      before each clinic visit. RESULTS: More frequent BGM was associated with better
      glycemic control. Evidence of a white coat adherence effect, with BGM frequency
      increasing before a clinic visit, was found only among children with low A1C
      levels. CONCLUSIONS: Highly motivated families who frequently monitor their
      child's blood glucose increased the frequency of BGM before the child's clinic
      visit. The additional monitoring may benefit the child by providing the physician
      with a wealth of blood glucose information to guide recommendations.

PMID- 21852679
TI  - Quality of medical care in diabetic women undergoing fertility treatment: we
      should do better!
AB  - OBJECTIVE: Diabetic women are at increased risk for adverse pregnancy outcomes
      that can be improved by preconception care. Our goal was to evaluate the quality
      of medical care in diabetic women who undergo fertility treatment and compare it
      with the quality of medical care in diabetic women with spontaneous pregnancies.
      RESEARCH DESIGN AND METHODS: This retrospective study on reproductive-age women
      undergoing fertility treatment in Clalit Health Services (CHS) used data on
      fertility treatments, prescription fillings, HbA(1c) levels, and demographics
      extracted from CHS computerized systems. The control group comprised women with
      spontaneous pregnancy. Three quality measures in the periconception period were
      evaluated: folic acid prescription fillings, evaluation and level of HbA(1c), and
      use of potentially hazardous drugs. RESULTS: There were 230 fertility treatment
      cycles in 83 diabetic women, and 30 diabetic women had spontaneous pregnancy.
      Women in the fertility group were older and had fewer children. There were no
      significant differences in marital status or ethnicity. Regular folic acid use,
      HbA(1c) recording, and the percentage of women with HbA(1c) <7% was similar
      between women in fertility treatment and those with spontaneous pregnancy (23.9,
      57.8, and 31.3% vs. 20.0, 73.3, and 40.0%, respectively). Several women in both
      groups continued the use of potentially hazardous medication. CONCLUSIONS: The
      periconception medical care of diabetic women who undergo fertility treatment is
      suboptimal and no better than that of diabetic women with spontaneous
      pregnancies. More intensive and targeted counseling regarding the importance of
      folic acid and glycemic control is needed to optimize periconception care of
      these diabetic patients.

PMID- 21852680
TI  - Low bone mineral density and its predictors in type 1 diabetic patients evaluated
      by the classic statistics and artificial neural network analysis.
AB  - OBJECTIVE: To investigate factors associated with bone mineral density (BMD) in
      type 1 diabetes by classic statistic and artificial neural networks. RESEARCH
      DESIGN AND METHODS: A total of 175 eugonadal type 1 diabetic patients (age 32.8
      +/- 8.4 years) and 151 age- and BMI-matched control subjects (age 32.6 +/- 4.5
      years) were studied. In all subjects, BMI and BMD (as Z score) at the lumbar
      spine (LS-BMD) and femur (F-BMD) were measured. Daily insulin dose (DID), age at
      diagnosis, presence of complications, creatinine clearance (ClCr), and HbA(1c)
      were determined. RESULTS: LS- and F-BMD levels were lower in patients (-0.11 +/-
      1.2 and -0.32 +/- 1.4, respectively) than in control subjects (0.59 +/- 1, P <
      0.0001, and 0.63 +/- 1, P < 0.0001, respectively). LS-BMD was independently
      associated with BMI and DID, whereas F-BMD was associated with BMI and ClCr. The
      cutoffs for predicting low BMD were as follows: BMI <23.5 kg/m(2), DID >0.67
      units/kg, and ClCr <88.8 mL/min. The presence of all of these risk factors had a
      positive predictive value, and their absence had a negative predictive value for
      low BMD of 62.9 and 84.2%, respectively. Data were also analyzed using the TWIST
      system in combination with supervised artificial neural networks and a semantic
      connectivity map. The TWIST system selected 11 and 12 variables for F-BMD and LS
      BMD prediction, which discriminated between high and low BMD with 67 and 66%
      accuracy, respectively. The connectivity map showed that low BMD at both sites
      was indirectly connected with HbA(1c) through chronic diabetes complications.
      CONCLUSIONS: In type 1 diabetes, low BMD is associated with low BMI and low ClCr
      and high DID. Chronic complications negatively influence BMD.

PMID- 21852681
TI  - Obesity in adults is associated with reduced lung function in metabolic syndrome
      and diabetes: the Strong Heart Study.
AB  - OBJECTIVE: The purposes of this study were to investigate whether reduced lung
      function is associated with metabolic syndrome (MS) and diabetes (DM) in American
      Indians (AIs) and to determine whether lower pulmonary function presents before
      the development of DM or MS. RESEARCH DESIGN AND METHODS: The Strong Heart Study
      (SHS) is a multicenter, prospective study of cardiovascular disease (CVD) and its
      risk factors among AI adults. The present analysis used lung function assessment
      by standard spirometry at the SHS second examination (1993-1995) in 2,396 adults
      free of overt lung disease or CVD, with or without DM or MS. Among MS-free/DM
      free participants, the development of MS/DM at the SHS third examination (1996
      1999) was investigated. RESULTS: Significantly lower pulmonary function was
      observed for AIs with MS or DM. Impaired pulmonary function was associated with
      MS and DM after adjustment for age, sex, abdominal obesity, current smoking
      status, physical activity index, hypertension, and SHS field center. Both forced
      vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were negatively
      associated with insulin resistance or DM severity and with serum markers of
      inflammation (P < 0.05). FVC and FEV1-to-FVC ratio both predicted DM in
      unadjusted analyses but not when adjusted for covariates, including waist
      circumference. In the adjusted model, abdominal obesity predicted both MS and DM.
      CONCLUSIONS: Reduced lung function is independently associated with MS and with
      DM, and impaired lung function presents before the development of MS or DM; these
      associations may result from the effects of obesity and inflammation.

PMID- 21852683
TI  - Evidence for functional atypical nicotinic receptors that activate K+-dependent
      Cl- secretion in mouse tracheal epithelium.
AB  - The present study focused on the influence of nicotinic acetylcholine receptors
      (nAChR) on ion transport processes in mouse tracheal epithelium. RT-PCR
      experiments revealed expression of the alpha3, alpha4, alpha5, alpha7, alpha9,
      alpha10, beta2, and beta4 nAChR subunits in mouse tracheal epithelium. In Ussing
      chamber recordings of mouse tracheae, apically applied nicotine (100 MUM) induced
      a dose-dependent increase of the transepithelial short-circuit current (EC(50):
      14.6 MUM). The nicotine-induced effect (I(NIC)) was attenuated by mecamylamine
      (25 MUM, apical) and methyllycaconitine (1 MUM, apical). The nAChR agonist 1.1
      dimethyl-4-phenylpiperatinium iodide (DMPP) (100 MUM) revealed apical and
      basolateral location of the receptors. I(NIC) was not affected by the sodium
      channel inhibitor amiloride (10 MUM, apical) or the cystic fibrosis transmembrane
      conductance regulator inhibitor CFTR(inh)-172 (20 MUM, apical) but was reduced by
      the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (100
      MUM, apical), the Na(+)/K(+)/2Cl(-) cotransporter inhibitor bumetanide (200 MUM,
      basolateral), the potassium channel inhibitor Ba(2+) (5 mM, basolateral), and
      4.4'-diisothiocyanatostilbene-2.2'-disulfonate (100 MUM, apical), indicating a
      contribution of Ca(2+)-activated chloride channels and potassium channels.
      Removal of extracellular Na(+) (apical) or Ca(2+) (apical) did not influence
      I(NIC) but reduced the DMPP effect. Experiments with the Ca(2+)-ionophore A23187,
      a mix of 3-isobutyl-1-methylxanthine and forskolin, or the inositol-1,4,5
      triphospate (IP(3)) receptor inhibitor 2-aminoethyl-diphenyl-borinate (75 MUM,
      apical) decreased I(NIC), indicating a nicotine-mediated increase of
      intracellular Ca(2+) and cAMP levels involving the IP(3) signaling pathway. These
      findings indicate the activity of Ca(2+)-permeable nAChRs and alternative
      metabotropic pathways by nAChR activation that mediate Cl(-) and K(+) transport
      in tracheal epithelium.

PMID- 21852682
TI  - Arc of a vicious circle: pathways activated by Mycobacterium tuberculosis that
      target the HIV-1 long terminal repeat.
AB  - In this review, we examine how a subset of signal transduction cascades initiated
      by Mycobacterium tuberculosis (Mtb) infection modulates transcription mediated by
      the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR). We
      describe two distinct phases of signaling that target transcription factors known
      to bind the HIV-1 LTR, and thus drive viral transcription and replication, in
      cells of the Mtb-infected host. First, Mtb-derived molecules, including cell wall
      components and DNA, interact with a number of host pattern recognition receptors.
      Second, cytokines and chemokines secreted in response to Mtb infection initiate
      signal transduction cascades through their cognate receptors. Given the variation
      in cell wall components among distinct clinical Mtb strains, the initial pattern
      recognition receptor interaction leading to direct LTR activation and
      differential cytokine and chemokine production is likely to be an important
      aspect of Mtb strain-specific regulation of HIV-1 transcription and replication.
      Improved understanding of these molecular mechanisms in the context of bacterial
      and host genetics should provide key insights into the accelerated viral
      replication and disease progression characteristic of HIV/TB coinfection.

PMID- 21852684
TI  - Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor
      1 for lung fibrosis.
AB  - Fibrosis is a final stage of many lung diseases, with no effective treatment.
      Plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of tissue-type and
      urokinase-type plasminogen activators (tPA and uPA, respectively), plays a
      critical role in the development of fibrosis. In this study, we explored the
      therapeutic potential of an orally effective small molecule PAI-1 inhibitor,
      TM5275, in a model of lung fibrosis induced by transforming growth factor-beta1
      (TGF-beta1), the most potent and ubiquitous profibrogenic cytokine, and in human
      lung fibroblasts (CCL-210 cells). The results show that an intranasal
      instillation of AdTGF-beta1(223/225), an adenovirus expressing constitutively
      active TGF-beta1, increased the expression of PAI-1 and induced fibrosis in
      murine lung tissue. On the other hand, treating mice with 40 mg/kg of TM5275 for
      10 days, starting 4 days after the instillation of AdTGF-beta1(223/225), restored
      the activities of uPA and tPA and almost completely blocked TGF-beta1-induced
      lung fibrosis, as shown by collagen staining, Western blotting, and the
      measurement of hydroxyproline. No loss of body weight was evident under these
      treatment conditions with TM5275. Furthermore, we show that TM5275 induced
      apoptosis in both myofibroblasts (TGF-beta1-treated) and naive (TGF-beta1
      untreated) human lung fibroblasts, and this apoptosis was associated with the
      activation of caspase-3/7, the induction of p53, and the inhibition of alpha
      smooth muscle actin, fibronectin, and PAI-1 expression. Such an inhibition of
      fibrotic responses by TM5275 occurred even in cells pretreated with TGF-beta1 for
      6 hours. Together, the results suggest that TM5275 is a relatively safe and
      potent antifibrotic agent, with therapeutic potential in fibrotic lung disease.

PMID- 21852685
TI  - Involvement of endoplasmic reticulum stress in myofibroblastic differentiation of
      lung fibroblasts.
AB  - Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation
      of unfolded or misfolded proteins in the ER (ER stress) and triggers the unfolded
      protein response (UPR). Recent studies suggest that ER stress is involved in
      idiopathic pulmonary fibrosis (IPF). The present study was undertaken to
      determine the role of ER stress on myofibroblastic differentiation of
      fibroblasts. Fibroblasts in fibroblastic foci of IPF showed immunoreactivity for
      GRP78. To determine the role of ER stress on alpha-smooth muscle actin (alpha
      SMA) and collagen type I expression in fibroblasts, mouse and human lung
      fibroblasts were treated with TGF-beta1, and expression of ER stress-related
      proteins, alpha-SMA, and collagen type I was analyzed by Western blotting. TGF
      beta1 significantly increased expression of GRP78, XBP-1, and ATF6alpha, which
      was accompanied by increases in alpha-SMA and collagen type I expression in mouse
      and human fibroblasts. A chemical chaperone, 4-PBA, suppressed TGF-beta1-induced
      UPR and alpha-SMA and collagen type I induction. We also showed that TGF-beta1
      induced UPR was mediated through the reactive oxygen species generation. Our
      study provides the first evidence implicating the UPR in myofibroblastic
      differentiation during fibrosis. These findings of the role of ER stress and
      chemical chaperones in pulmonary fibrosis may improve our understanding of the
      pathogenesis of IPF.

PMID- 21852686
TI  - Roles for beta-catenin and doxycycline in the regulation of respiratory
      epithelial cell frequency and function.
AB  - The expression of beta-catenin-dependent genes can be increased through the Cre
      recombinase (Cre)-mediated elimination of the exon 3-encoded sequence. This
      mutant beta-catenin is termed DE3, and promotes the expression of beta-catenin
      dependent genes. Our previous study used the DE3 model to demonstrate that
      persistent beta-catenin activity inhibited bronchiolar Clara-to-ciliated cell
      differentiation. The present study was designed to evaluate the roles of beta
      catenin in regulating the tracheal progenitor cell hierarchy. However, initial
      experiments demonstrated that the tetracycline-responsive element-Cre transgene
      (TRE-Cre) was active in the absence of a reverse tetracycline transactivator
      driver or inducer, doxycycline (Dox). This spurious TRE-Cre transgene activity
      was not detected using the ROSA26-floxed STOP-LacZ reporter. To determine if the
      phenotype was a consequence of genotype or treatment with Dox, tracheal and lung
      specimens were evaluated using quantitative histomorphometric techniques.
      Analyses of uninduced mice demonstrated a significant effect of genotype on
      tracheal epithelial cell mass, involving basal, Clara-like cell types. The
      bronchial and bronchiolar Clara cell mass was also decreased. Paradoxically, an
      effect on ciliated cell mass was not detected. Activation of the beta-catenin
      reporter transgene TOPGal demonstrated that beta-catenin-dependent gene
      expression led to the genotype-dependent tracheal and bronchiolar phenotype.
      Comparative analyses of wild-type or keratin 14-rtTA(+/0)/TRE-cre(+/0)/DE3(+/+)
      mice receiving standard or Dox chow demonstrated an effect of treatment with Dox
      on basal, Clara-like, and Clara cell masses. We discuss these results in terms of
      cautionary notes and with regard to alterations of progenitor cell hierarchies in
      response to low-level injury.

PMID- 21852687
TI  - Allergen-induced airway remodeling in brown norway rats: structural and metabolic
      changes in glycosaminoglycans.
AB  - Increased proteoglycan (PG) deposition is a feature of airway remodeling in
      asthma. Glycosaminoglycans (GAGs) mediate many of the biological and mechanical
      properties of PGs by providing docking sites through their carbohydrate chains to
      bioactive ligands; therefore, it is imperative to define structural and metabolic
      changes of GAGs in asthma. Using a Brown Norway (BN) ovalbumin (OVA)-sensitized
      and -challenged rat model to induce airway remodeling, we found excessive
      deposition of chondroitin/dermatan (CS/DS)-, heparan (HS), and keratan (KS)
      sulfate GAGs in the airways and bronchoalveolar lavage cells of OVA-challenged
      rats. Disaccharide composition of CS/DS of OVA-challenged rats was significantly
      different compared with saline-treated (SAL) control rats, with increased levels
      of 0-, 6-, and 4-sulfated disaccharides. Increases in the amount and a change in
      the proportion of CS/DS versus HS GAGs were noted in OVA-challenged rats. The
      higher content and sulfation of CS/DS disaccharides was reflected by the
      increased expression of xylosyltransferase-I, beta1,3-glucuronosyltransferase-I,
      chondroitin-4, and chondroitin-6 sulfotransferase genes and protein expression of
      xylosyltransferase-I and beta1,3-glucuronosyltransferase-I in OVA-challenged
      rats. Genes encoding the core proteins of the CS/DS and KS-containing PGs, such
      as versican, biglycan, decorin, and lumican, were overexpressed in OVA-challenged
      rats. Our results suggest that GAG biosynthetic enzymes may be involved in the
      altered expression of GAGs in the airways and are potential targets for
      inhibiting excess PG-GAG deposition and the airway remodeling process in asthma.

PMID- 21852688
TI  - Tissue factor pathway inhibitor attenuates the progression of malignant pleural
      mesothelioma in nude mice.
AB  - Malignant pleural mesothelioma (MPM) is a rare cancer that is refractory to
      current treatments. It is characterized by a robust deposition of transitional
      fibrin that is in part promoted by tumor cells. MPM cells express tissue factor
      (TF) and the tissue factor pathway inhibitor (TFPI), but their contribution to
      the pathogenesis of MPM has been unclear. We found that REN MPM cells fail to
      express TFPI. Based on the tumor growth-promoting properties of TF, we
      hypothesized that the stable transfection of TFPI into REN MPM cells would
      decrease their aggressiveness. We tested our hypothesis using in vitro, in vivo,
      and ex vivo analyses. TFPI knock-in decreased the proliferation, invasion, and TF
      activity of REN cells in vitro. REN TFPI knock-in cells, empty vector, and naive
      control cells were next injected intrapleurally into nude mice. The expression of
      TFPI significantly decreased tissue invasion, inflammation, and the deposition of
      fibrin and collagen associated with tumor tissue, pleural effusions, and tumor
      burden. In ex vivo analyses, REN cells were cultured from harvested tumors. The
      overexpression of TFPI was maintained in cells propagated from TFPI knock-in
      tumors, and attenuated the activation of Factor X and the invasiveness of tumor
      cells. These analyses demonstrate that TFPI reduces the aggressiveness of MPM in
      vitro and in vivo, and that its effect involves the inhibition of TF procoagulant
      activity. These observations suggest that the interactions of TF and TFPI
      represent a novel therapeutic target in the treatment of MPM.

PMID- 21852689
TI  - Substance Abuse and HIV/AIDS in the Caribbean.
AB  - The Caribbean and Central America represent a formidable challenge for
      researchers and policy makers in the HIV field, due to their pronounced
      heterogeneity in terms of social, economic, and cultural contexts and the
      different courses the HIV epidemic has followed in the region. Such contrasting
      contexts and epidemics can be exemplified by 2 countries that share the island of
      Hispaniola, the French Creole-speaking Haiti, and the Spanish-speaking Dominican
      Republic. Haiti has experienced the worst epidemics outside of sub-Saharan
      Africa. Following a protracted economic and social crisis, recently aggravated by
      a devastating earthquake, the local HIV epidemic could experience resurgence. The
      region, strategically located on the way between coca-producing countries and the
      profitable North American markets, has been a transshipment area for years.
      Notwithstanding, the impact of such routes on local drug scenes has been very
      heterogeneous and dynamic, depending on a combination of local mores, drug
      enforcement activities, and the broad social and political context. Injecting
      drug use remains rare in the region, but local drug scenes are dynamic under the
      influence of increasing mobility of people and goods to and from North and South
      America, growing tourism and commerce, and prostitution. The multiple impacts of
      the recent economic and social crisis, as well as the influence of drug
      trafficking routes across the Caribbean and other Latin American countries
      require a sustained effort to track changes in the HIV risk environment to inform
      sound drug policies and initiatives to minimize drug-related harms in the region.

PMID- 21852690
TI  - Stereoselective oxidation of regioisomeric octadecenoic acids by fatty acid
      dioxygenases.
AB  - Seven Z-octadecenoic acids having the double bond located in positions 6Z to 13Z
      were photooxidized. The resulting hydroperoxy-E-octadecenoic acids [HpOME(E)]
      were resolved by chiral phase-HPLC-MS, and the absolute configurations of the
      enantiomers were determined by gas chromatographic analysis of diastereoisomeric
      derivatives. The MS/MS/MS spectra showed characteristic fragments, which were
      influenced by the distance between the hydroperoxide and carboxyl groups. These
      fatty acids were then investigated as substrates of cyclooxygenase-1 (COX-1),
      manganese lipoxygenase (MnLOX), and the (8R)-dioxygenase (8R-DOX) activities of
      two linoleate diol synthases (LDS) and 10R-DOX. COX-1 and MnLOX abstracted
      hydrogen at C-11 of (12Z)-18:1 and C-12 of (13Z)-18:1. (11Z)-18:1 was subject to
      hydrogen abstraction at C-10 by MnLOX and at both allylic positions by COX-1.
      Both allylic hydrogens of (8Z)-18:1 were also abstracted by 8R-DOX activities of
      LDS and 10R-DOX, but only the allylic hydrogens close to the carboxyl groups of
      (11Z)-18:1 and (12Z)-18:1. 8R-DOX also oxidized monoenoic C(14)-C(20) fatty acids
      with double bonds at the (9Z) position, suggesting that the length of the omega
      end has little influence on positioning for oxygenation. We conclude that COX-1
      and MnLOX can readily abstract allylic hydrogens of octadecenoic fatty acids from
      C-10 to C-12 and 8R-DOX from C-7 and C-12.

PMID- 21852691
TI  - Triclosan affects the thyroid axis of amphibians.

PMID- 21852694
TI  - Genetic testing.

PMID- 21852692
TI  - Helicobacter felis--associated gastric disease in microbiota-restricted mice.
AB  - Human Helicobacter pylori infection leads to multiple pathological consequences,
      including gastritis and adenocarcinoma. Although this association has led to the
      classification of H. pylori as a type 1 carcinogen, it is not clear if additional
      nonhelicobacter gastric microbiota play a role in these diseases. In this study,
      we utilized either specific pathogen-free C57BL/6 mice (B6.SPF) or mice colonized
      with altered Schaedler flora (B6.ASF) to evaluate the role of nonhelicobacter
      gastric microbiota in disease development after Helicobacter felis infection.
      Despite similar histological changes, H. felis persisted in B6.ASF stomachs,
      while H. felis could no longer be detected in the majority of B6.SPF mice. The
      B6.SPF mice also acquired multiple Lactobacillus spp. in their stomachs after H.
      felis infection. Our data indicate that potential mechanisms responsible for the
      ineffective H. felis clearance in the B6.ASF model include the absence of new
      gastric microbiota to compete for the gastric niche, the lack of expression of
      new gastric mucins, and a reduced ratio of H. felis-specific IgG2c:IgG1 serum
      antibodies. These data suggest that although H. felis is sufficient to initiate
      gastric inflammation and atrophy, bacterial eradication and the systemic immune
      response to infection are significantly influenced by pre-existing and acquired
      gastric microbiota.

PMID- 21852695
TI  - Genetic profiling tests in screening for cardiovascular disease.

PMID- 21852696
TI  - Vitamin D and rickets: much has been accomplished, but there is room for
      improvement.

PMID- 21852697
TI  - Universal antenatal screening for group B streptococcus in Emilia-Romagna.
AB  - BACKGROUND: Group B streptococcus (GBS) is a leading cause of severe infections
      in newborns. Intrapartum antibiotic chemoprophylaxis (IAP) reduces the rate of
      early-onset disease. The aim of this study is to determine the degree of
      clinicians' compliance with the suggested protocol for GBS prevention in Emilia
      Romagna (Italy). METHODS: Characteristics of each delivery were prospectively
      recorded in the period between October 2005 to December 2005. Standardized pro
      forma were used to collect data. RESULTS: Among 5118 babies, 7.2% (369) were
      preterm and 92.3% were born at term (4749). Antenatal screening was performed in
      86.6% of women who delivered at term, of which 18.1% were GBS culture-positive.
      Information regarding culture site was available in 93.2% of women screened and
      recto-vaginal cultures were documented in 42.7%. IAP was administered to 28.7% of
      3937 women at term who had either spontaneous delivery or emergency caesarean
      section. In this cohort, 15.9% were diagnosed GBS culture-positive, of which
      92.6% received IAP. Prophylaxis was also administered to 8.4% (331) of women for
      no apparent reason. Compared with tertiary level hospitals, women delivering in
      primary/secondary hospitals were more likely to be both GBS screened (P < 0.0001;
      OR 3.04; CI 2.33-3.97) and to receive prophylaxis >=4 hours before delivery (P =
      0.0025; OR 1.57; CI 1.17-2.12). CONCLUSIONS: GBS screening was performed in >85%
      of women and >90% of culture-positive women received prophylaxis. However, there
      is a need to educate clinicians about protocol adherence, as most cultures were
      suboptimal and cases of unnecessary IAP were administered. The screening was more
      effective in hospitals with fewer deliveries.

PMID- 21852698
TI  - Impact on informed choice of offering antenatal sickle cell and thalassaemia
      screening in primary care: a randomized trial.
AB  - OBJECTIVES: Offering antenatal sickle cell and thalassaemia (SCT) screening early
      in pregnancy can maximize the range of post-screening choices available, however
      these benefits should not be obtained at the expense of informed choice.  This
      study examined whether offering this screening in primary care at the time of
      pregnancy confirmation compromises women making informed choices. Design Partial
      factorial, cluster randomized controlled trial. SETTING: 25 general practices in
      two socially deprived UK areas. Participants 464 pregnant women offered antenatal
      SCT screening. Intervention Practices were randomly allocated to offer pregnant
      women screening:  i) in primary care at time of pregnancy confirmation, with
      parallel partner testing (n = 191), ii) in primary care at time of pregnancy
      confirmation, with sequential partner testing (n = 158), or iii) in secondary
      care by midwives, with sequential partner testing (standard care, n = 115). Main
      outcome Informed choice - a classification based on attitudes, knowledge and test
      uptake. RESULTS: 91% of woman underwent screening. About a third (30.6%) made an
      informed choice to accept or decline screening: 34% in primary care parallel
      group; 23.4% in primary care sequential and 34.8% in secondary care sequential.
      Allowing for adjustments, rates of informed choice did not vary by intervention
      group: secondary care versus primary care with parallel partner testing OR 1.07
      (95% CI 0.56 to 2.02); secondary care versus primary care with sequential partner
      testing OR 0.67 (95% CI 0.36 to 1.25).  Uninformed choices were generally
      attributable to poor knowledge (65%). CONCLUSION: Offering antenatal SCT
      screening in primary care did not reduce the likelihood that women made informed
      choices. Rates of informed choice were low and could be increased by improving
      knowledge.

PMID- 21852699
TI  - Indirect comparison of two quantitative immunochemical faecal occult blood tests
      in a population with average colorectal cancer risk.
AB  - Magstream and OC Sensor quantitative immunochemical faecal occult blood tests
      (IFOBT) have shown better performances than guaiac (G) tests in colorectal cancer
      screening, however Magstream and OC Sensor have never been compared. We
      hypothesized that similar performances could be observed with Magstream and OC
      Sensors, provided a similar cut-off (expressed in concentration of haemoglobin in
      the stools) is used. We performed a literature-based indirect comparison between
      these tests, taking into account the cut-off, the number of samples, and the way
      they were combined (I(2+): at least one positive sample of 2; I(2++): both
      positive samples; I(1): only one sample). Six studies conducted in general
      average-risk populations were included in this review. For each [test]*[cut-off],
      positivity rate (PR) decreased and predictive positive value (PPV) increased from
      I(2+) to I(1) and I(2++.) For similar PR, PPV with OC Sensor was greater than
      with Magstream. This could be due to factors other than the test, because PPVs
      associated with GFOBT in studies evaluating OC Sensor were greater than PPVs
      associated with GFOBT in the study evaluating Magstream. Direct comparison
      between Magstream and OC Sensor is needed to confirm the suspected superiority of
      OC Sensor.

PMID- 21852700
TI  - High yield of colorectal neoplasia detected by colonoscopy following a positive
      faecal occult blood test in the NHS Bowel Cancer Screening Programme.
AB  - OBJECTIVES: The UK National Health Service Bowel Cancer Screening Programme
      (BCSP) is based on a strategy of biennial faecal occult blood (FOB) testing.
      Positive results are classified as 'abnormal' or 'weak positive' based on the
      number of positive windows per kit or need for repeat testing. Colonoscopy is
      offered to both groups. We evaluate the relationship between FOB test positivity
      and clinical outcome in the BCSP. SETTING: The South of Tyne and Tees (UK) Bowel
      Cancer Screening Centres. METHODS: Data were collected prospectively on all
      individuals who were offered FOB testing and colonoscopy between February 2007
      and February 2009. Univariable and multivariable analyses were performed to
      investigate the relationship between FOB test positivity and clinical outcome.
      RESULTS: Following FOB testing, 1524 individuals underwent colonoscopy, 1259
      (83%) after a 'weak positive' and 265 (17%) an 'abnormal' result. Cancer was
      detected in 180 (11.8%) and adenomas in 758 (49.7%). Individuals with an
      'abnormal' result were more likely to have cancer or be 'high risk' for the
      development of future adenomas (110/265, 41.5%) than those with 'weak positive'
      results, (236/1259, 18.7%, P < 0.0001). Those with Dukes stage B, C or D cancers
      or cancers proximal to the splenic flexure were more likely to have an 'abnormal'
      result. CONCLUSIONS: The majority of colonoscopies were performed following 'weak
      positive' FOB results. Those with an 'abnormal' result were more likely to be
      diagnosed with cancer. The high yield of pathology in both the 'abnormal' and
      'weak positive' groups justifies the need for colonoscopy in both.

PMID- 21852702
TI  - Screening outcomes in women over age 70 who self-refer in the NHSBSP in England.
AB  - SETTING: The NHS breast screening programme (NHSBSP) in England currently invites
      women aged 50-70 every three years. Whilst screening is acknowledged as
      efficacious for women aged 50-69, several countries routinely invite women up to
      the age of 74. The NHSBSP in England is beginning to invite women up to the age
      of 73. Although the incidence of breast cancer increases with age, the possible
      benefits of screening older women must be balanced against shorter life
      expectancies and possible overdiagnosis. In England women can self-refer after
      reaching the invitation upper age limit. OBJECTIVE: We examined the extent to
      which older women in England self-referred over a three-year period and studied
      the screening outcomes in these women. METHODS: Routinely collected data from
      screening units in England were used to calculate screening performance measures
      for women who self-referred between 1 April 2005 and 31 March 2008. The tumour
      characteristics of all screen-detected cancers were examined by previous
      screening history and age group (71-74 and >=75 years). RESULTS: During the three
      year period 139,910 women aged over 70 self-referred; equivalent to 4% of the
      female population aged over 70 having been screened. The majority of women who
      self-referred had been screened within the previous five years (76% of those aged
      71-74 and 65% of those aged 75 or over). Approximately 4% of these women were
      recalled for assessment and cancer detection rates were similar in both age
      groups. CONCLUSION: Only a small proportion of all women aged over 70 utilize the
      self-referral policy of the NHSBSP, and most such women are aged below 80.

PMID- 21852701
TI  - Narrowing the equity gap: the impact of organized versus opportunistic cancer
      screening in Catalonia (Spain).
AB  - OBJECTIVES: To assess the impact on equity of access of an organized breast
      cancer screening programme, compared with opportunistic breast and cervical
      cancer screening activities. METHODS: Two cross-sectional health interview
      surveys conducted in 1994 and 2006 in Catalonia (Spain), with 6382 and 7653 women
      participating in both surveys. The main outcome measures were having undergone
      regular mammography, and regular cytology. Age-standardized prevalence rates for
      both screening tests were computed using the direct method. The relative
      inequality index was computed to measure changes over time in inequality on
      screening utilization. RESULTS: Participation among women aged 50-69 has
      increased after the introduction of the organized breast screening programme; the
      greatest impact has been observed among those women with lower educational levels
      (from 17% in 1994 to 79% in 2006). Equity of access by education was particularly
      increased in the target group for breast cancer screening. CONCLUSION: This study
      indicates that an organized screening programme could improve participation and
      equity of access.

PMID- 21852703
TI  - Extending the age range for breast screening in England: pilot study to assess
      the feasibility and acceptability of randomization.
AB  - OBJECTIVE: To assess the feasibility and acceptability of randomizing the phased
      introduction of the extension of the invited age range in the National Health
      Service (NHS) Breast Screening Programme in England from 50-70 to 47-73 years.
      SETTING: Six volunteer breast screening units (BSUs) in England. METHODS: Cluster
      randomized trial of invitation versus no invitation for breast screening. STUDY
      PARTICIPANTS: women aged 47-49 and 71-73 years in screening batches randomized
      between 1 June 2009 and 31 May 2010. OUTCOMES: workload, screening uptake among
      women invited, self-referrals among women not invited, and screening outcomes
      among women invited. RESULTS: A total of 312 screening batches (clusters) were
      randomized including 60,708 women. Screening uptake was 63% in women aged 47-49
      and 62% in women aged 71-73. Those who attended screening in the younger age
      group were more likely to be recalled for assessment than older attendees (7.5%
      vs. 3.0%) but less likely to be diagnosed with breast cancer (0.5% vs. 1.1%).
      Among women not invited, 0.2% of those aged 47-49 and 6.8% of those aged 71-73
      self-referred for screening. Despite the extra workload BSUs largely coped
      although there was some slippage in round lengths and other targets. CONCLUSION:
      No major problems of feasibility or acceptability of randomization were found.
      This pilot study has informed the randomized phasing-in of the age extension
      across the whole of England.

PMID- 21852705
TI  - Colorectal cancer screening, ethics and evidence-based public policy.

PMID- 21852706
TI  - How should screeners respond to women's distress about unexpected DCIS
      uncertainties?

PMID- 21852708
TI  - A fruity note: crossmodal associations between odors and musical notes.
AB  - Odors are notoriously difficult to describe, but they seem prone to a variety of
      crossmodal associations. In the present study, we generalize the previously-shown
      association between odors (from perfumery) and pitch (Belkin et al. 1997) to
      odors related to food and drink (in this case those associated with wine). We
      also demonstrate that, to a lesser extent (25% of the odor tested), participants
      preferentially match specific odors to certain types of instruments. The ratings
      of the odors along a number of dimensions are used in principal components
      analysis (PCA) to explore the psychological dimensions underlying the odor-pitch
      associations. The results demonstrate that both pleasantness and complexity, but
      not intensity, appear to play a role when choosing a pitch to match an odor. Our
      results suggest that these features of odor stimuli constitute psychological
      dimensions that can be consistently matched to auditory features.

PMID- 21852709
TI  - Function and immunocytochemical localization of two novel odorant-binding
      proteins in olfactory sensilla of the scarab beetle Holotrichia oblita Faldermann
      (Coleoptera: Scarabaeidae).
AB  - Odorant-binding proteins (OBPs) are found in both insects and vertebrates, and it
      is believed that they are involved in chemical communication. In this study, we
      identify and express 2 OBPs from the scarab beetle, Holotrichia oblita Faldermann
      (Coleoptera: Scarabaeidae). HoblOBP1 shows more similarities with other scarab
      beetle OBPs, whereas HoblOBP2 is more diverse. N-phenyl-1-naphthylamine (1-NPN)
      is used as a fluorescent probe in ligand-binding experiment, and results indicate
      that both HoblOBPs prefer plant volatiles to putative H. oblita sex pheromones.
      HoblOBP1 shows binding affinity to a wider range of test compounds, but HoblOBP2
      displays more specific binding affinity. Cinnamaldehyde and 2,4-di-tert
      butylphenol bind to HoblOBP1 can elicit strong electrophysiological responses of
      the antennae from female H. oblita adults, respectively. Methyl salicylate also
      shows good affinity to HoblOBP2 and it can elicit moderate electrophysiological
      responses. Although, beta-ionone is one of the ligands of the strongest binding,
      it elicits a weak electrophysiological response. In the immunocytochemical
      analysis, we observe that HoblOBP1 and HoblOBP2 are coexpressed in sensilla
      basiconica and placodea in both sexes.

PMID- 21852710
TI  - Vitamin D and HIV: letting the sun shine in.
AB  - Vitamin D is important for cell growth, immunity, and metabolism. Deficiency has
      classically been associated with rickets and decreased bone density and more
      recently with increased risk and severity of autoimmune diseases, cancers,
      myocardial infarction, diabetes, and infectious diseases. How vitamin D can
      affect these diverse conditions is the subject of much research. The active form
      of vitamin D (vitamin D3) has been implicated recently in an intracellular
      process known as autophagy. In addition to its role in maintaining cellular
      homeostasis during conditions of stress, autophagy plays an important role in the
      control of many intracellular microorganisms including Mycobacterium
      tuberculosis. Recent work has identified that HIV-1 reduces autophagy during
      permissive infection and that agents that induce autophagy, including vitamin D3,
      can inhibit HIV-1 replication. These findings help provide a biological
      explanation for the increased risk of more rapid disease progression observed in
      HIV-infected persons with low levels of vitamin D or with genetic variants within
      the vitamin D receptor that alter binding to vitamin D. Controlled trials are
      needed to determine the potential for therapeutic benefit of vitamin D
      supplementation in HIV disease. This article summarizes a presentation by Stephen
      A. Spector, MD, at the IAS-USA continuing medical education program held in
      Chicago in April 2010.

PMID- 21852711
TI  - Retention in HIV care: what the clinician needs to know.
AB  - Poor retention in HIV disease care is a common, modifiable risk factor associated
      with poor outcomes, including higher rates of antiretroviral therapy failure,
      increased HIV transmission risk behaviors, and worse survival. Predictors of poor
      retention include younger age, female sex, racial or ethnic minority status, low
      socioeconomic status, no usual source of health care, less advanced HIV disease,
      fewer non-HIV-related comorbidities, and greater unmet psychosocial needs. Thus
      far, there have been few published randomized trials of interventions to improve
      retention. The fact that most clinics are understaffed and underresourced in a
      flat funding environment raises serious questions about the translation,
      dissemination, and sustainability of interventions found to be successful in the
      research setting. Efforts to improve retention in care should incorporate
      informational, motivational, and behavioral skills components. Practical steps
      can be taken by clinics to improve retention. This article summarizes a lecture
      by Thomas P. Giordano, MD, MPH, at the 13th Annual Clinical Conference for the
      Ryan White HIV/AIDS Program held in Washington, DC, in August 2010.

PMID- 21852712
TI  - HIV diagnostic testing: evolving technology and testing strategies.
AB  - Detection of acute HIV infection is important to public health because this stage
      is one of high infectiousness and appears to account for a disproportionate
      amount of HIV transmission. Newer technologies in HIV testing, including third
      generation enzyme immunoassays (EIAs) that detect anti-HIV IgM and IgG
      antibodies, fourth-generation combination EIAs that detect both anti-HIV
      antibodies and HIV p24 antigen, and nucleic acid-based testing for HIV RNA, have
      markedly reduced the interval between infection and detection of infection. Rapid
      diagnostic tests including assays for IgG and IgM anti-HIV antibodies have high
      sensitivity and specificity. The availability and wide use of these newer
      technologies have motivated review of recommended HIV testing algorithms.
      Individuals' knowledge of their HIV serostatus contributes to reducing
      transmission risk behaviors. Thus, widespread testing, facilitated by newer
      technology, allows more individuals to know their serostatus and is the first
      step in any successful effort to curb the incidence of HIV infection. This
      article summarizes a lecture by Demetre Daskalakis, MD, at the New York City IAS
      USA continuing medical education program held in November 2009 and re-presented
      in December 2010.

PMID- 21852713
TI  - Prevention of perinatal HIV transmission: the Perinatal HIV Hotline perspective.
AB  - Among the most frequently asked questions by callers to the National Perinatal
      HIV Hotline are those on the use of hormonal contraception in women receiving
      antiretroviral therapy. Estradiol levels are reduced by ritonavir-boosted
      protease inhibitors (PIs), nelfinavir, and nevirapine and increased by non
      ritonavir-boosted PIs (except nelfinavir), efavirenz, and etravirine. Oral
      contraceptives do not affect antiretroviral drug levels, and several options are
      available for hormonal contraception that can compensate for or avoid the effects
      of antiretroviral drugs on estrogen levels. Other common questions on the hotline
      involve interpretation and management issues that arise from indeterminate
      Western blot test results early and late in pregnancy and from positive rapid
      test results during labor. Many questions focus on appropriate selection of
      antiretroviral drugs in pregnancy and the need to change regimens to reduce risk
      of birth defects in the child. This articlesummarizes a presentation by Jess
      Fogler Waldura, MD, at the 13th Annual Clinical Conference for the Ryan White
      HIV/AIDS Program held in August 2010 in Washington, DC.

PMID- 21852714
TI  - A biomimetic robotic jellyfish (Robojelly) actuated by shape memory alloy
      composite actuators.
AB  - An analysis is conducted on the design, fabrication and performance of an
      underwater vehicle mimicking the propulsion mechanism and physical appearance of
      a medusa (jellyfish). The robotic jellyfish called Robojelly mimics the
      morphology and kinematics of the Aurelia aurita species. Robojelly actuates using
      bio-inspired shape memory alloy composite actuators. A systematic fabrication
      technique was developed to replicate the essential structural features of A.
      aurita. Robojelly's body was fabricated from RTV silicone having a total mass of
      242 g and bell diameter of 164 mm. Robojelly was able to generate enough thrust
      in static water conditions to propel itself and achieve a proficiency of 0.19 s(
      1) while the A. aurita achieves a proficiency of around 0.25 s(-1). A thrust
      analysis based on empirical measurements for a natural jellyfish was used to
      compare the performance of the different robotic configurations. The
      configuration with best performance was a Robojelly with segmented bell and a
      passive flap structure. Robojelly was found to consume an average power on the
      order of 17 W with the actuators not having fully reached a thermal steady state.

PMID- 21852715
TI  - Effect of outer wing separation on lift and thrust generation in a flapping wing
      system.
AB  - We explore the implementation of wing feather separation and lead-lagging motion
      to a flapping wing. A biomimetic flapping wing system with separated outer wings
      is designed and demonstrated. The artificial wing feather separation is
      implemented in the biomimetic wing by dividing the wing into inner and outer
      wings. The features of flapping, lead-lagging, and outer wing separation of the
      flapping wing system are captured by a high-speed camera for evaluation. The
      performance of the flapping wing system with separated outer wings is compared to
      that of a flapping wing system with closed outer wings in terms of forward force
      and downward force production. For a low flapping frequency ranging from 2.47 to
      3.90 Hz, the proposed biomimetic flapping wing system shows a higher thrust and
      lift generation capability as demonstrated by a series of experiments. For 1.6 V
      application (lower frequency operation), the flapping wing system with separated
      wings could generate about 56% higher forward force and about 61% less downward
      force compared to that with closed wings, which is enough to demonstrate larger
      thrust and lift production capability of the separated outer wings. The
      experiments show that the outer parts of the separated wings are able to deform,
      resulting in a smaller amount of drag production during the upstroke, while still
      producing relatively greater lift and thrust during the downstroke.

PMID- 21852716
TI  - On designing geometric motion planners to solve regulating and trajectory
      tracking problems for robotic locomotion systems.
AB  - Based on a geometric fiber bundle structure, a generalized method to solve both
      regulation and trajectory tracking problems for locomotion systems is presented.
      The method is especially applied to two case studies of robotic locomotion
      systems; a three link articulated fish-like robot as a prototype of locomotion
      systems with symmetry, and the snakeboard as a prototype of mixed locomotion
      systems. Our results show that although these motion planners have an open loop
      structure, due to their generalities, they can steer case studies with negligible
      errors for almost any complicated path.

PMID- 21852717
TI  - A two-dimensional DNA lattice implanted polymer solar cell.
AB  - A double crossover tile based artificial two-dimensional (2D) DNA lattice was
      fabricated and the dry-wet method was introduced to recover an original DNA
      lattice structure in order to deposit DNA lattices safely on the organic layer
      without damaging the layer. The DNA lattice was then employed as an electron
      blocking layer in a polymer solar cell causing an increase of about 10% up to
      160% in the power conversion efficiency. Consequently, the resulting solar cell
      which had an artificial 2D DNA blocking layer showed a significant enhancement in
      power conversion efficiency compared to conventional polymer solar cells. It
      should be clear that the artificial DNA nanostructure holds unique physical
      properties that are extremely attractive for various energy-related and photonic
      applications.

PMID- 21852718
TI  - Electrochemical development of hydrogen silsesquioxane by applying an electrical
      potential.
AB  - We present a new method for developing hydrogen silsesquioxane (HSQ) by using
      electrical potentials and deionized water. Nested-L test structures with a pitch
      as small as 9 nm were developed using this electrochemical technique in saline
      solution without adding hydroxyl ions. Furthermore, we showed that high
      resolution structures can be electrochemically developed in deionized water
      alone. Electrochemical development is controlled by the applied voltage and may
      overcome several of the limitations discussed for alkaline developers, such as
      poor hydroxyl anion diffusion and charge repulsion effects in small trenches.

PMID- 21852719
TI  - Accumulation of silver nanoparticles by cultured primary brain astrocytes.
AB  - Silver nanoparticles (AgNP) are components of various food industry products and
      are frequently used for medical equipment and materials. Although such particles
      enter the vertebrate brain, little is known on their biocompatibility for brain
      cells. To study the consequences of an AgNP exposure of brain cells we have
      treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated
      AgNP. The incubation of cultured astrocytes with micromolar concentrations of
      AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation
      of silver, but did not compromise the cell viability nor lower the cellular
      glutathione content. In contrast, the incubation of astrocytes for 4 h with
      identical amounts of silver as AgNO(3) already severely compromised the cell
      viability and completely deprived the cells of glutathione. The accumulation of
      AgNP by astrocytes was proportional to the concentration of AgNP applied and
      significantly lowered by about 30% in the presence of the endocytosis inhibitors
      chloroquine or amiloride. Incubation at 4  degrees C reduced the accumulation of
      AgNP by 80% compared to the values obtained for cells that had been exposed to
      AgNP at 37  degrees C. These data demonstrate that viable cultured brain
      astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent
      process that most likely involves endocytotic pathways.

PMID- 21852720
TI  - Electron beam synthesis of metal and semiconductor nanoparticles using metal
      organic frameworks as ordered precursors.
AB  - We demonstrate a versatile, bottom-up method of forming metal and semiconducting
      nanoparticles by exposing precursor metal-organic frameworks (MOFs) to an
      electron beam. Using a transmission electron microscope to initiate and observe
      growth, we show that the composition, size, and morphology of the nanoparticles
      are determined by the chemistry and structure of the MOF, as well as the electron
      beam properties. Zinc oxide, metallic indium and copper particles were produced
      with narrow and tunable size distributions comparable to those obtained from
      state-of-the-art methods. This method represents a first step toward the
      fabrication of nanoscale heterostructures using the highly controlled environment
      of the MOF pores as a scaffold or template.

PMID- 21852721
TI  - Magnetic recyclable Ag catalysts with a hierarchical nanostructure.
AB  - This study reports the fabrication of a novel hierarchically structured
      nanocatalyst system possessing a well-defined nickel silicate (NS) protected
      Fe(3)O(4) core and a layer of uniform Ag nanoparticles on the NS shell by using a
      multi-step approach. The multifunctional microparticles show high performance in
      the reduction of 4-nitrophenol and the rate of the catalytic reaction can be
      controlled by changing the concentration of nanocatalysts. In particular, there
      was no visible decrease in the catalytic activity of the reused catalysts even
      after being recycled five times. Thus the hierarchically structured Fe(3)O(4)@NS
      particles are very suitable as a catalyst support for catalyst separation and
      redispersion.

PMID- 21852722
TI  - Improved performance of ZnO nanowire field-effect transistors via focused ion
      beam treatment.
AB  - A seven orders of magnitude increase in the current on/off ratio of ZnO nanowire
      field-effect transistors (FETs) after Ga( + ) irradiation was observed.
      Transmission electron microscopy characterization revealed that the surface
      crystal quality of the ZnO nanowire was improved via the Ga( + ) treatment. The
      Ga( + ) irradiation efficiently reduces chemisorption effects and decreases
      oxygen vacancies in the surface layer. The enhanced performance of the nanowire
      FET was attributed to the decrease of surface trapped electrons and the decrease
      in carrier concentration.

PMID- 21852723
TI  - Characterization of a high-purity germanium detector for small-animal SPECT.
AB  - We present an initial evaluation of a mechanically cooled, high-purity germanium
      double-sided strip detector as a potential gamma camera for small-animal SPECT.
      It is 90 mm in diameter and 10 mm thick with two sets of 16 orthogonal strips
      that have a 4.5 mm width with a 5 mm pitch. We found an energy resolution of
      0.96% at 140 keV, an intrinsic efficiency of 43.3% at 122 keV and a FWHM spatial
      resolution of approximately 1.5 mm. We demonstrated depth-of-interaction
      estimation capability through comparison of pinhole acquisitions with a point
      source on and off axes. Finally, a flood-corrected flood image exhibited a strip
      level uniformity of less than 1%. This high-purity germanium offers many
      desirable properties for small-animal SPECT.

PMID- 21852724
TI  - Spatial shrinkage/expansion patterns between breast density measured in two MRI
      scans evaluated by non-rigid registration.
AB  - Breast MRI acquires many images from the breast, and computer-aided algorithms
      and display tools are often used to assist the radiologist's interpretation.
      Women with lifetime risk greater than 20% of developing breast cancer are
      recommended to receive annual screening MRI, but the current breast MRI computer
      aided-diagnosis systems do not provide the necessary function for comparison of
      images acquired at different times. The purpose of this work was to develop
      registration methods for evaluating the spatial change pattern of fibroglandular
      tissue between two breast MRI scans of the same woman taken at different times.
      The registration method is based on rigid alignment followed by a non-rigid
      Demons algorithm. The method was tested on three different subjects who had
      different degrees of changes in the fibroglandular tissue, including two patients
      who showed different spatial shrinkage patterns after receiving neoadjuvant
      chemotherapy before surgery, and one control case from a normal volunteer. Based
      on the transformation matrix, the collapse of multiple voxels on the baseline
      images to one voxel on the follow-up images is used to calculate the shrinkage
      factor. Conversely, based on the reverse transformation matrix the expansion
      factor can be calculated. The shrinkage/expansion factor, the deformation
      magnitude and direction, as well as the Jacobian determinate at each location can
      be displayed in a 3D rendering view to show the spatial changes between two MRI
      scans. These different parameters show consistent results and can be used for
      quantitative evaluation of the spatial change patterns. The presented
      registration method can be further developed into a clinical tool for evaluating
      therapy-induced changes and for early diagnosis of breast cancer in screening
      MRI.

PMID- 21852725
TI  - Computational high-resolution heart phantoms for medical imaging and dosimetry
      simulations.
AB  - Cardiovascular disease in general and coronary artery disease (CAD) in
      particular, are the leading cause of death worldwide. They are principally
      diagnosed using either invasive percutaneous transluminal coronary angiograms or
      non-invasive computed tomography angiograms (CTA). Minimally invasive therapies
      for CAD such as angioplasty and stenting are rendered under fluoroscopic
      guidance. Both invasive and non-invasive imaging modalities employ ionizing
      radiation and there is concern for deterministic and stochastic effects of
      radiation. Accurate simulation to optimize image quality with minimal radiation
      dose requires detailed, gender-specific anthropomorphic phantoms with
      anatomically correct heart and associated vasculature. Such phantoms are
      currently unavailable. This paper describes an open source heart phantom
      development platform based on a graphical user interface. Using this platform, we
      have developed seven high-resolution cardiac/coronary artery phantoms for imaging
      and dosimetry from seven high-quality CTA datasets. To extract a phantom from a
      coronary CTA, the relationship between the intensity distribution of the
      myocardium, the ventricles and the coronary arteries is identified via histogram
      analysis of the CTA images. By further refining the segmentation using anatomy
      specific criteria such as vesselness, connectivity criteria required by the
      coronary tree and image operations such as active contours, we are able to
      capture excellent detail within our phantoms. For example, in one of the female
      heart phantoms, as many as 100 coronary artery branches could be identified.
      Triangular meshes are fitted to segmented high-resolution CTA data. We have also
      developed a visualization tool for adding stenotic lesions to the coronaries. The
      male and female heart phantoms generated so far have been cross-registered and
      entered in the mesh-based Virtual Family of phantoms with matched age/gender
      information. Any phantom in this family, along with user-defined stenoses, can be
      used to obtain clinically realistic projection images with the Monte Carlo code
      penMesh for optimizing imaging and dosimetry.

PMID- 21852726
TI  - Improved contrast deep optoacoustic imaging using displacement-compensated
      averaging: breast tumour phantom studies.
AB  - For real-time optoacoustic (OA) imaging of the human body, a linear array
      transducer and reflection mode optical irradiation is usually preferred. Such a
      setup, however, results in significant image background, which prevents imaging
      structures at the ultimate depth determined by the light distribution and the
      signal noise level. Therefore, we previously proposed a method for image
      background reduction, based on displacement-compensated averaging (DCA) of image
      series obtained when the tissue sample under investigation is gradually deformed.
      OA signals and background signals are differently affected by the deformation and
      can thus be distinguished. The proposed method is now experimentally applied to
      image artificial tumours embedded inside breast phantoms. OA images are acquired
      alternately with pulse-echo images using a combined OA/echo-ultrasound device.
      Tissue deformation is accessed via speckle tracking in pulse echo images, and
      used to compensate in the OA images for the local tissue displacement. In that
      way, OA sources are highly correlated between subsequent images, while background
      is decorrelated and can therefore be reduced by averaging. We show that image
      contrast in breast phantoms is strongly improved and detectability of embedded
      tumours significantly increased, using the DCA method.

PMID- 21852727
TI  - Single-layer and dual-layer contrast-enhanced mammography using amorphous
      selenium flat panel detectors.
AB  - The accumulation of injected contrast agents allows the image enhancement of
      lesions through the use of contrast-enhanced mammography. In this technique, the
      combination of two acquired images is used to create an enhanced image. There
      exist several methods to acquire the images to be combined, which include dual
      energy subtraction using a single detection layer that suffers from motion
      artifacts due to patient motion between image acquisition. To mitigate motion
      artifacts, a detector composed of two layers may be used to simultaneously
      acquire the low and high energy images. In this work, we evaluate both of these
      methods using amorphous selenium as the detection material to find the system
      parameters (tube voltage, filtration, photoconductor thickness and relative
      intensity ratio) leading to the optimal performance. We then compare the
      performance of the two detectors under the variation of contrast agent
      concentration, tumor size and dose. The detectability was found to be most
      comparable at the lower end of the evaluated factors. The single-layer detector
      not only led to better contrast, due to its greater spectral separation
      capabilities, but also had lower quantum noise. The single-layer detector was
      found to have a greater detectability by a factor of 2.4 for a 2.5 mm radius
      tumor having a contrast agent concentration of 1.5 mg ml(-1) in a 4.5 cm thick
      50% glandular breast. The inclusion of motion artifacts in the comparison is part
      of ongoing research efforts.

PMID- 21852728
TI  - Anisotropy of acceptor states in lightly doped cuprate superconductors.
AB  - We investigate the role of short wavelength antiferromagnetic correlations in the
      spatial structure of acceptor states doped into a two-dimensional Mott-Hubbard
      antiferromagnetic insulator. We extend the traditional effective mass
      approximation, by using the Green's function formalism and its spectral
      representation, and we show that when the electronic scattering at the ordering
      wavevector Q = (pi,pi) is strong enough to produce a momentum dependent
      scattering rate, Gamma(k), the corresponding acceptor state envelope wavefunction
      becomes spatially anisotropic. Finally, we discuss the connection between our
      results and photoemission spectra in lightly doped La(2-x)Sr(x)CuO(4).

PMID- 21852729
TI  - Modulation of leading edge vorticity and aerodynamic forces in flexible flapping
      wings.
AB  - In diverse biological flight systems, the leading edge vortex has been implicated
      as a flow feature of key importance in the generation of flight forces. Unlike
      fixed wings, flapping wings can translate at higher angles of attack without
      stalling because their leading edge vorticity is more stable than the
      corresponding fixed wing case. Hence, the leading edge vorticity has often been
      suggested as the primary determinant of the high forces generated by flapping
      wings. To test this hypothesis, it is necessary to modulate the size and strength
      of the leading edge vorticity independently of the gross kinematics while
      simultaneously monitoring the forces generated by the wing. In a recent study, we
      observed that forces generated by wings with flexible trailing margins showed a
      direct dependence on the flexural stiffness of the wing. Based on that study, we
      hypothesized that trailing edge flexion directly influences leading edge
      vorticity, and thereby the magnitude of aerodynamic forces on the flexible
      flapping wings. To test this hypothesis, we visualized the flows on wings of
      varying flexural stiffness using a custom 2D digital particle image velocimetry
      system, while simultaneously monitoring the magnitude of the aerodynamic forces.
      Our data show that as flexion decreases, the magnitude of the leading edge
      vorticity increases and enhances aerodynamic forces, thus confirming that the
      leading edge vortex is indeed a key feature for aerodynamic force generation in
      flapping flight. The data shown here thus support the hypothesis that camber
      influences instantaneous aerodynamic forces through modulation of the leading
      edge vorticity.

PMID- 21852730
TI  - An x-ray scattering study of the structural phase transition in La(2
      x)Sr(x)Cu0.99Fe0.01O4 (x = 0.20).
AB  - We report a comprehensive x-ray scattering study of the low-temperature
      orthorhombic (LTO)-high-temperature tetragonal (HTT) structural phase transition
      in 1% iron-doped La(2-x)Sr(x)CuO(4) (x = 0.2). The superlattice (032) peak
      intensity and the width are investigated in detail for a wide temperature range.
      We found that the structural phase transition is not sharp and the tilt ordering
      of the CuO(6) octahedra persists above the transition temperature T(S) (~77 K).
      Even at room temperature, the superlattice peak is still observable. The
      structural phase transition is identified as an order-disorder type phase
      transition. We found that the tilt ordering in our iron-doped material is always
      short-ranged, and in the HTT phase the correlation between the tilts along the b
      axis is better preserved than that along the a axis. Moreover, we identify the
      role of the Fe as the nucleation centers of the LTO domains in the structural
      phase transition.

PMID- 21852731
TI  - The effect of external pressure on the magnetocaloric effect of Ni-Mn-In alloy.
AB  - The martensitic transition in Ni(50)Mn(34)In(16) alloy has been studied by
      measuring the magnetization of the alloy as a function of temperature, magnetic
      field and pressure. Magnetic field and pressure have opposite effects on the
      martensitic transition in this alloy; the martensitic transition temperature
      decreases with increasing magnetic field but it increases with increasing
      pressure. The effect of pressure on the magnetocaloric properties of this large
      magnetocaloric effect alloy has been investigated in detail. The magnitude of the
      peak in the isothermal magnetic entropy change in Ni(50)Mn(34)In(16) increases
      with pressure. The temperature at which the magnetocaloric effect reaches the
      peak value in this alloy increases from near 240 K under ambient pressure to near
      280 K under an external pressure of 9.5 kbar. The temperature corresponding to
      the peak in the isothermal magnetic entropy change increases with increasing
      pressure at a rate which matches the rate of increase of the martensite start
      temperature with increasing pressure. The temperature dependence of the
      isothermal magnetic entropy change under different pressures is found to follow a
      universal curve for a particular magnetic field change. These results show that
      pressure as a control parameter can be used to tune the temperature regime of the
      magnetocaloric effect in the alloy. The effect of pressure on the martensitic
      transition also gives a clue as regards the possibility of tuning this
      temperature regime with elemental substitution.

PMID- 21852732
TI  - The quantum anomalous Hall effect in kagome lattices.
AB  - The quantum anomalous Hall (QAH) effect in kagome lattices is investigated in the
      presence of both Rashba spin-orbit coupling and an exchange field. In addition to
      the gap at the Dirac points as found in graphene, a new topological energy gap is
      opened at the Gamma point. With the Fermi energy lying in the first gap, the
      Chern number = 2 as in graphene, whereas with it lying in the second one, = 1.
      The distribution of Berry curvature is obtained to reveal the nontrivial
      topological properties in momentum space. For stripes with 'armchair' and
      'zigzag' edges, the topological characteristics of gapless edge states on the
      genus g = 2 Riemann surface are studied. The obtained nonzero winding numbers
      also demonstrate the QAH effe

PMID- 21852733
TI  - Role of AAO template filling process parameters in controlling the structure of
      one-dimensional polymer nanoparticles.
AB  - Solution template wetting is a common technique used to fabricate elongated
      polymer nanostructures; however, the parameters controlling the resulting
      morphology remain unclear. The purpose of this investigation was to elucidate the
      effects of process variables on the types of nanostructures obtained and to
      understand the physical mechanisms associated with structure development. 1 wt%
      polystyrene-THF solutions were infiltrated into commercial and homemade anodized
      aluminum oxide (AAO) templates. The wetting interaction between the AAO template
      and the polymer solution was examined through contact angle measurements. In
      general, for moderate dipping times (<18 h), the morphology of the nanopolymer
      was rod-like at low molecular weights, while tubes were observed at high
      molecular weight, even at this low concentration. Nanorods were obtained for all
      molecular weights for extended dipping times. The data suggest that phase
      separated layers may grow sequentially from the pore walls and yield nanotubes if
      the growth is interrupted or produce nanorods for unhindered deposition over long
      periods.

PMID- 21852734
TI  - Nanoscale surface photovoltage of organic semiconductors with two pass Kelvin
      probe microscopy.
AB  - Kelvin probe microscopy implemented with controlled sample illumination is used
      to study nanoscale surface photovoltage effects. With this objective a two trace
      method, where each scanning line is measured with and without external
      illumination, is proposed. This methodology allows a direct comparison of the
      contact potential images acquired in darkness and under illumination and,
      therefore, the surface photovoltage is simply inferred. Combined with an
      appropriate data analysis, the temporal and spatial evolution of reversible and
      irreversible photo-induced processes can be obtained. The potential and
      versatility of this technique is applied to MEH-PPV thin films. Photo-physical
      phenomena such as the mesoscale polymer electronic light-induced response as well
      as the local nanoscale electro-optical properties are studied.

PMID- 21852735
TI  - Nonlinear and magneto-optical transmission studies on magnetic nanofluids of non
      interacting metallic nickel nanoparticles.
AB  - Oxide free stable metallic nanofluids have the potential for various applications
      such as in thermal management and inkjet printing apart from being a candidate
      system for fundamental studies. A stable suspension of nickel nanoparticles of ~
      5 nm size has been realized by a modified two-step synthesis route. Structural
      characterization by x-ray diffraction and transmission electron microscopy shows
      that the nanoparticles are metallic and are phase pure. The nanoparticles
      exhibited superparamagnetic properties. The magneto-optical transmission
      properties of the nickel nanofluid (Ni-F) were investigated by linear optical
      dichroism measurements. The magnetic field dependent light transmission studies
      exhibited a polarization dependent optical absorption, known as optical
      dichroism, indicating that the nanoparticles suspended in the fluid are non
      interacting and superparamagnetic in nature. The nonlinear optical limiting
      properties of Ni-F under high input optical fluence were then analyzed by an open
      aperture z-scan technique. The Ni-F exhibits a saturable absorption at moderate
      laser intensities while effective two-photon absorption is evident at higher
      intensities. The Ni-F appears to be a unique material for various optical devices
      such as field modulated gratings and optical switches which can be controlled by
      an external magnetic field.

PMID- 21852736
TI  - Optical evidence of a quantum well channel in low temperature molecular beam
      epitaxy grown Ga(AsBi)/GaAs nanostructure.
AB  - A Ga(AsBi) quantum well (QW) with Bi content reaching 6% and well width of 11 nm
      embedded in GaAs is grown by molecular beam epitaxy at low temperature and
      studied by means of high-resolution x-ray diffraction, photoluminescence (PL),
      and time-resolved PL. It is shown that for this growth regime, the QW is
      coherently strained to the substrate with a low dislocation density. The low
      temperature PL demonstrates a comparatively narrow excitonic linewidth of ~ 40
      meV. For high excitation density distinct QW excited states evolve in the
      emission spectra. The origins of peculiar PL dependences on temperature and
      excitation density are interpreted in terms of intra-well optical transitions.

PMID- 21852737
TI  - Sub-10 nm patterning using EUV interference lithography.
AB  - Extreme ultraviolet (EUV) lithography is currently considered as the leading
      technology for high-volume manufacturing below sub-20 nm feature sizes. In
      parallel, EUV interference lithography based on interference transmission
      gratings has emerged as a powerful tool for industrial and academic research. In
      this paper, we demonstrate nanopatterning with sub-10 nm resolution using this
      technique. Highly efficient and optimized molybdenum gratings result in resolved
      line/space patterns down to 8 nm half-pitch and show modulation down to 6 nm half
      pitch. These results show the performance of optical nanopatterning in the sub-10
      nm range and currently mark the record for photon-based lithography. Moreover, an
      efficient phase mask completely suppressing the zeroth-order diffraction and
      providing 50 nm line/space patterns over large areas is evaluated. Such efficient
      phase masks pave the way towards table-top EUV interference lithography systems.

PMID- 21852738
TI  - Conformational behavior of DNA-templated CdS inorganic nanowire.
AB  - We describe the conformational behavior and morphological control of DNA
      mineralized CdS nanowires in a bulk solution. The conformational behavior of
      individual double-stranded DNA in the presence of cadmium ions and stoichiometric
      mixtures of cadmium ions and sulfide ions was directly visualized by fluorescence
      microscopy. It was found that in the presence of mixtures of cadmium ions and
      sulfide ions, DNA molecules exhibit a conformational transition from an elongated
      coil to a compacted state. Mineralized DNA nanowires possess a significant
      conformational freedom at a microscale, and flexibility in the micro- and
      nanodimensions. The density of the inorganic material on the nanowire can be
      controlled by varying the concentrations and the molar ratio of Na(2)S to
      Cd(ClO(4))(2).

PMID- 21852739
TI  - A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and
      biocompatible gene delivery vector.
AB  - Non-viral gene delivery systems based on cationic polymers have faced limitations
      related to their relative low gene transfer efficiency, cytotoxicity and system
      instability in vivo. In this paper, a flexible and pompon-like dendrimer composed
      of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid)
      grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple
      arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to
      combine the merits of size-controlled PAMAM G4.0 and the low toxicity and
      flexible chains of PLGE. In phosphate-buffered saline dispersions the well
      defined DNA/MGI complex above a N/P ratio of 30 showed good stability with
      particle sizes of approximately 200 nm and a comparatively low polydispersity
      index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI
      25K) complex was larger than 700 nm under the same salt conditions. The shielding
      of the compact amino groups at the periphery of flexible PAMAM and biocompatible
      PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared
      to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI
      dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in
      serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained
      the same high levels of transfection efficiency as in serum-free medium, while
      the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000
      were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into
      balloon-injured rabbit carotid arteries resulted in significant inhibition of
      restenosis by increasing VEGF165 expression in local vessels. Therefore, the
      pompon-like MGI dendrimer may be a promising vector candidate for efficient gene
      delivery in vivo.

PMID- 21852740
TI  - Synthesis of highly magnetic graphite-encapsulated FeCo nanoparticles using a
      hydrothermal process.
AB  - The graphite encapsulation of metal alloy magnetic nanoparticles has attracted
      attention for biological applications because of the high magnetization of the
      encapsulated particles. However, most of the synthetic methods have limitations
      in terms of scalability and economics because of the demanding synthetic
      conditions and low yields. Here, we show that well controlled graphite
      encapsulated FeCo core-shell nanoparticles can be synthesized by a hydrothermal
      method, simply by mixing Fe/Co with sucrose as a carbon source. Various Fe/Co
      metal ratios were used to determine the compositional dependence of the
      saturation magnetization and relaxivity coefficient. Transmission electron
      microscopy indicated that the particle sizes were 7 nm. In order to test the
      capability of graphite-encapsulated FeCo nanoparticles as magnetic resonance
      imaging (MRI) contrast agents, these nanoparticles were solubilized in water by
      the nonspecific physical adsorption of sodium dodecylbenzene sulfonate.

PMID- 21852741
TI  - Phosphine-free synthesis of high-quality reverse type-I ZnSe/CdSe core with
      CdS/Cd(x)Zn(1 - x)S/ZnS multishell nanocrystals and their application for
      detection of human hepatitis B surface antigen.
AB  - Highly photoluminescent (PL) reverse type-I ZnSe/CdSe nanocrystals (NCs) and
      ZnSe/CdSe/CdS/Cd(x)Zn(1 - x)S/ZnS core/multishell NCs were successfully
      synthesized by a phosphine-free method. By this low-cost, 'green' synthesis
      route, more than 10 g of high-quality ZnSe/CdSe/CdS/Cd(x)Zn(1 - x)S/ZnS NCs were
      synthesized in a large scale synthesis. After the overgrowth of a CdS/Cd(x)Zn(1 -
      x)S/ZnS multishell on ZnSe/CdSe cores, the PL quantum yields (QYs) increased from
      28% to 75% along with the stability improvement. An amphiphilic oligomer was used
      as a surface coating agent to conduct a phase transfer experiment,
      core/multishell NCs were dissolved in water by such surface modification and the
      QYs were still kept above 70%. The as-prepared water dispersible
      ZnSe/CdSe/CdS/Cd(x)Zn(1 - x)S/ZnS core/multishell NCs not only have high
      fluorescence QYs but also are extremely stable in various physiological
      conditions. Furthermore, a biosensor system (lateral flow immunoassay system,
      LFIA) for the detection of human hepatitis B surface antigen (HBsAg) was
      developed by using this water-soluble core/multishell NCs as a fluorescent label
      and a nitrocellulose filter membrane for lateral flow. The result showed that
      such ZnSe/CdSe/CdS/Cd(x)Zn(1 - x)S/ZnS core/multishell NCs were excellent
      fluorescent labels to detect HBsAg. The sensitivity of HBsAg detection could
      reach as high as 0.05 ng ml( - 1).

PMID- 21852742
TI  - Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to
      acute and chronic stress.
AB  - Detailed dynamics of the hypothalamic-pituitary-adrenal (HPA) axis is complex,
      depending on the individual metabolic load of an organism, its current status
      (healthy/ill, circadian phase (day/night), ultradian phase) and environmental
      impact.  Therefore, it is difficult to compare the HPA axis activity between
      different individuals or draw unequivocal conclusions about the overall status of
      the HPA axis in an individual using single time-point measurements of cortisol
      levels.  The aim of this study is to identify parameters that enable us to
      compare different dynamic states of the HPA axis and use them to investigate self
      regulation mechanisms in the HPA axis under acute and chronic stress.  In this
      regard, a four-dimensional stoichiometric model of the HPA axis was used.  Acute
      stress was modeled by inducing an abrupt change in cortisol level during the
      course of numerical integration, whereas chronic stress was modeled by changing
      the mean stationary state concentrations of CRH.  Effects of acute stress
      intensity, duration and time of onset with respect to the ultradian amplitude,
      ultradian phase and the circadian phase of the perturbed oscillation were studied
      in detail.  Bifurcation analysis was used to predict the response of the HPA axis
      to chronic stress.  Model predictions were compared with experimental findings
      reported in the literature and relevance for pharmacotherapy with glucocorticoids
      was discussed.

PMID- 21852743
TI  - Determination of triacylglycerol composition in vegetable oils using high
      performance liquid chromatography: a collaborative study.
AB  - Triacylglycerol (TAG) composition in vegetable oils was collaboratively analyzed
      in 9 laboratories using high-performance liquid chromatography (HPLC) equipped
      with a refractive index detector. Dococyl (C22) and triacontyl (C30) silica
      columns were used for analysis. The TAG molecular species in soybean, rapeseed,
      and palm oils were individually separated on the chromatogram. The collaborative
      study demonstrated that TAG composition in vegetable oils could be analyzed based
      on partition numbers (PN) between 38 and 50. In conclusion, the HPLC method using
      C22 and C30 silica columns would be useful for determining the TAG composition
      (%) in vegetable oils.

PMID- 21852744
TI  - Gallic acid glycerol ester promotes weight-loss in rats.
AB  - Lifestyle-related diseases arise from obesity in 30 - 60% of cases. In recent
      years, food functions controlling the nutritional physiology of lipids have been
      a focus of disease prevention. Animal feeding experiments have revealed that
      esters made from gallic acid (GA) and (-)-epigallo-catechin (EGC) or linoleyl
      alcohol are more effective in weight-loss promotion and metabolic syndrome
      management than are intact GA and EGC. In this study, an ester (DOGGA) was
      chemically synthesized from GA and 1,2-dioleoyl glycerol and its effect was
      compared to that of octyl gallate (OG) and GA in male Wistar rats fed a powdered
      standard diet containing 7% frying oil for 12 weeks. Results revealed remarkably
      low body weight gains and food efficiency ratios in the DOGGA group, and the
      effects of OG were less pronounced than those of DOGGA. The GA group showed no
      difference from the control group. In addition, fecal lipid content in the DOGGA
      group was statistically higher than that in the control group, although organ
      weights and serum biochemical analyses did not differ between the groups. In
      conclusion, the data suggested that DOGGA promoted weight-loss more effectively
      than OG and GA did and that the alcohol moiety of gallate is not necessarily EGC
      and linoleyl alcohol.

PMID- 21852745
TI  - A study on fatty acids in seeds of Euterpe oleracea Mart seeds.
AB  - Fatty acids of Euterpe oleracea Mart seeds were analyzed in hexane and diethyl
      ether extracts. The hexane extract contained dodecanoic acid (3), tetradecanoic
      acid (4), hexadecanoic acid (7), and 9-octadecenoic acid (10). The diethyl ether
      extract contained (10). The oil of Mart seeds was obtained firstly by methanol
      extract and further extracted with diethyl ether. The hexane and diethyl ether
      extracts were then analyzed for antioxidant effects. Both extracts demonstrated a
      1,1-diphenyl-2-picrylhydrazyl radical elimination effect similar to that of alpha
      tocopherol and an active oxygen inhibition effect. Significant quantities (0.6212
      mg/mL) of polyphenol, in comparison to the standard rejected gallic acid, were
      found in the extract oil of Mart seeds by the methanol extraction.

PMID- 21852746
TI  - Aqueous solution properties of disulfide-linked fluorinated gemini and cleaved
      monomeric thiol surfactants.
AB  - We prepared a fluorinated gemini surfactant containing a disulfide bond in its
      spacer chain, [C8F17(CH2)3N(CH3)2CH2CH2SSCH2CH2N(CH3)2(CH2)3C8F17]2Cl, and its
      analogue with a hexamethylene spacer. Monomeric thiol surfactant,
      [C8F17(CH2)3N(CH3)2CH2CH2SH]Cl, was readily produced by the cleavage of the
      gemini surfactant using dithiothreitol in water. The critical micelle
      concentration was determined using surface tension, conductivity, and
      fluorescence probe methods. The critical micelle concentration of the monomeric
      surfactant was significantly larger than that of the gemini surfactant. The
      surface tension of aqueous solution for the cleaved monomeric thiol surfactant
      returned gradually to the original value through the formation of the disulfide
      bond via air oxidation.

PMID- 21852747
TI  - Detection of genes involved in fatty acid elongation and desaturation in
      thraustochytrid marine eukaryotes.
AB  - Heterotrophic marine protists known as thraustochytrids can synthesize
      polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The
      biosynthetic pathways of PUFAs in thraustochytrids are poorly understood,
      however. In this study, we attempted to reveal the enzymes involved in DHA
      synthesis in thraustochytrids. Nine thraustochytrid strains representing 3 genera
      (Aurantiochytrium, Schizochytrium, and Thraustochytrium) were used for PCR-based
      detection of the genes encoding Delta5-elongase and Delta4-desaturase and for
      fatty acid analysis. The degenerate primers were designed to amplify the Delta5
      elongase and Delta4-desaturase genes, and the partial sequences of the enzymes
      were obtained from the genera Thraustochytrium and Schizochytrium. These
      fragments were identical to those of known Delta5-elongase and Delta4-desaturase.
      Neither Delta5-elongase nor Delta4-desaturase was detected in the strains
      belonging to the genus Aurantiochytrium, however, suggesting that this group
      likely synthesizes DHA not via the elongation/desaturation pathway but via an
      alternate pathway such as the polyketide synthase pathway. The fatty acid
      profiles of thraustochytrids were consistent with the presence of genes involved
      in PUFA biosynthesis in thraustochytrid genera. Thus, our findings suggest that
      two biosynthetic pathways for PUFAs exist in these organisms.

PMID- 21852748
TI  - Synthesis of dilinoleoyl-D-glyceric acid and evaluation of its cytotoxicity to
      human dermal fibroblast and endothelial cells.
AB  - A novel derivative of glyceric acid (GA), dilinoleoyl-D-glyceric acid (LA2-DGA),
      was synthesized from D-GA calcium salt and linoleoyl chloride and evaluated for
      cytotoxicity. The D-GA calcium salt was first reacted with 4
      methoxybezylchloride, and the resulting compound was esterified with linoleoyl
      chloride. This reaction was followed by hydrolysis of the 4-methoxybenzyl moiety,
      yielding LA2-DGA. LA2-DGA was then subjected to cytotoxicity testing using normal
      human dermal fibroblasts and primary normal human dermal microvascular
      endothelial cells. LA2-DGA showed no significant toxic effects in either type of
      cell.

PMID- 21852749
TI  - Membrane-bound alcohol dehydrogenase is essential for glyceric acid production in
      Acetobacter tropicalis.
AB  - Acetobacter tropicalis NBRC16470 can produce highly enantiomerically pure D
      glyceric acid (D-GA; >99 % enantiomeric excess) from glycerol. To investigate
      whether membrane-bound alcohol dehydrogenase (mADH) is involved in GA production
      in A. tropicalis, we amplified part of the gene encoding mADH subunit I (adhA)
      using polymerase chain reaction and constructed an adhA-disrupted mutant of A.
      tropicalis (DeltaadhA). Because DeltaadhA did not produce GA, we confirmed that
      mADH is essential for the conversion of glycerol to GA. We also cloned and
      sequenced the entire region corresponding to adhA and adhB, which encodes mADH
      subunit II. The sequences showed high identities (84-86 %) with the equivalent
      mADH subunits from other Acetobacter spp.

PMID- 21852750
TI  - Intranasal administration of semaphorin-3A alleviates sneezing and nasal rubbing
      in a murine model of allergic rhinitis.
AB  - Sneezing and persistent itching of the nasal mucosa are distressing symptoms of
      allergic rhinitis (AR). Recent studies have revealed that hyperinnervation of
      sensory neurons in the nasal turbinate is one of the underlying causes of
      sneezing and itching. Since Semaphorin-3A (Sema3A) has been previously shown to
      restrict innervation of sensory neurons, it is presumed that reduced Sema3A
      expression in the nasal mucosa might contribute to the hypersensitivity. Analysis
      of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression
      of Sema3A in the nasal epithelium, which was accompanied by an increased nerve
      fiber density in the lamina propria of the turbinate. In rescue experiments,
      intranasal administration of recombinant Sema3A in the AR model mice alleviated
      sneezing and nasal rubbing symptoms. In addition, histological examinations also
      revealed that nerve fiber density was decreased in the lamina propria of the
      Sema3A-treated nasal turbinate. These results suggest that the nasal
      hypersensitivity of AR may be attributed to reduction of Sema3A expression and
      intranasal administration of Sema3A may provide a novel approach to alleviate the
      allergic symptoms for AR treatment.

PMID- 21852751
TI  - Probucol attenuates inflammation and increases stability of vulnerable
      atherosclerotic plaques in rabbits.
AB  - Probucol, a lipid-lowering agent with anti-oxidant properties, has been
      implicated in protection against atherogenesis, whereas its effect on plaques
      stability remains to be fully elucidated. The present study was aimed to test the
      hypothesis that probucol may attenuate inflammation and increase stability of
      vulnerable atherosclerotic plaques using a rabbit model. After abdominal aortic
      balloon injury, 45 rabbits were fed a 1% cholesterol diet for 24 weeks. From week
      12 to week 24, the animals were treated with probucol (1% by weight in the diet),
      simvastatin (5 mg.kg(-1), positive control) or no drugs (control), respectively.
      At the end of week 22, recombinant-p53 adenovirus was injected into the abdominal
      aortic plaques. Two weeks later, plaque disruption was induced by injection of
      Chinese Russell's viper venom and histamine. The results showed that the
      incidence of plaque disruption in probucol or simvastatin groups was
      significantly lower than that in the control group (7.15% or 14.29% vs. 71.43%
      respectively, both P < 0.01). Probucol significantly increased the thickness of
      fibrous caps and decreased plaque vulnerability index. Serum concentrations of
      inflammatory cytokines and matrix metalloproteinases, and expression levels of
      Toll-like receptor (TLR)-2, TLR-4, monocyte chemoattractant protein-1,
      intercellular adhesion molecule 1, scavenger receptor A, CD36 and oxidized low
      density lipoprotein receptor 1 within the lesions were markedly lower in both
      treatment groups than in the control group. We conclude that probucol increases
      the stability of vulnerable plaques, possibly through its lipid lowering, anti
      inflammation and scavenger receptors suppression effects, suggesting probucol as
      a promising pharmacologic approach to stabilize vulnerable plaques.

PMID- 21852752
TI  - The M protein of group A Streptococcus is a key virulence factor and a clinically
      relevant strain identification marker.
AB  - The M protein coats group A streptococci (GAS) and acts as the primary antigen
      and determinant of type-specific immunity. M is essential for GAS virulence,
      providing antiphagocytic functions critical to survival in human tissues and
      fluids. Specific regions of M protein also serve as shared antigens, and cross
      reactivity between these epitopes and human proteins may be the source of
      autoimmune sequelae such as rheumatic heart disease. The M protein is
      hypervariable, and has long served as the primary target for epidemiological
      typing of GAS. Though other markers or genotyping methods may be necessary to
      increase strain resolution when clones of a given M type differ in clinically
      critical ways, M typing remains the most directly informative and well-documented
      method for tracking outbreaks of GAS, predicting clinical outcomes during those
      outbreaks, and measuring the general threat presented by GAS at any given time
      and place.

PMID- 21852753
TI  - The higher expression levels of dehydroascorbate reductase and glutathione
      reductase in salicylic acid-deficient plants may contribute to their alleviated
      symptom infected with RNA viruses.
AB  - Salicylic acid (SA) is a critical signal for activation of both local and
      systemic resistance responses. However, SA-deficient plants adapt to RNA virus
      infections better, which show a less-severe symptom and less reactive oxygen
      species (ROS) accumulation. The higher levels of reduced glutathione (GSH) and
      reduced ascorbic acid (AsA) in SA-deficient plants may contribute to their
      alleviated symptoms, which are consistent with their higher expression levels of
      dehydroascorbate reductase gene (DHAR) and glutathione reductase gene (GR). High
      dose AsA or GSH treatment could alleviate the symptom and inhibit virus
      replication after 20 days, but ROS eliminators could not imitate the effect of
      AsA or GSH. The data show a new link between SA and AsA/GSH-mediated redox
      homeostasis.

PMID- 21852754
TI  - Tissue-specific organelle DNA degradation mediated by DPD1 exonuclease.
AB  - Organelle DNA in plastids and mitochondria is present in multiple copies and
      undergoes degradation developmentally. For example, organelle DNA that is
      detectable cytologically using DNA-fluorescent dye disappears during pollen
      development. Nevertheless, nucleases involved in this degradation process remain
      unknown. Our recent study identified the organelle nuclease, DPD1, which has Mg2+
      -dependent exonuclease activity in vitro. The discovery of DPD1 emerged from
      Arabidopsis mutant screening and concomitant isolation of dpd1 mutants that
      retain organelle DNA in mature pollen. DPD1 is conserved only in angiosperms: not
      in other photosynthetic organisms. Despite these findings, the physiological
      significance of organelle DNA degradation during pollen development remains
      unclear because dpd1 exhibits no apparent defects in pollen viability or in the
      maternal inheritance of organelle DNA. We discuss a possible role of organelle
      DNA degradation mediated by DPD1, based on a DPD1 expression profile studied
      using in silico analyses.

PMID- 21852755
TI  - PIN polarity regulation by AGC-3 kinases and ARF-GEF: a recurrent theme with
      context dependent modifications for plant development and response.
AB  - The analysis of cell polarity in plants is fueled by the discovery and analysis
      of auxin efflux carrier PIN proteins that show polar localizations in various
      plant cell types in line with their roles in directional cell to cell auxin
      transport. As this asymmetry in cellular PIN localization drives directional
      auxin fluxes, abnormalities in PIN localizations modify auxin transport
      culminating into range of auxin distribution defective phenotypes. Because of
      this influence of PIN localization on plant development via changes in auxin
      distribution, mechanisms establishing, maintaining and altering PIN polarity are
      of intense interest in the plant field during the recent years. Recent findings
      suggest that two categories of molecules, namely AGC-3 kinase family members
      PINOID, WAG1, WAG2 and ARF-GEF family member GNOM predominantly influence the
      polar localization of PINs. The emerging mechanism for AGC-3 kinases and ARF-GEF
      action suggest that AGC-3 kinases predominantly phosphorylate PINs at the plasma
      membrane for eventual PIN internalization and PIN sorting into ARF-GEF GNOM
      independent polar recycling pathways. In case of mutant for AGC-3 kinases or
      mutations in AGC-3 kinase-targeted PIN residues, much less phosphorylated PINs
      are recruited into ARFGEF GNOM-dependent polar recycling pathway. When ARF-GEF
      GNOM is inactive, the bias is shifted for rerouting less efficiently
      phosphorylated PINs into GNOM-independent polar recycling pathways that generally
      prefer efficiently phosphorylated PINs. Thus, balance shifts between the extent
      of AGC-3 kinase mediated PIN phosphorylation and the functioning of ARFGEF
      instruct PIN polarity establishment and/or PIN polarity alterations. Recent
      studies report utilization of this AGC-3 kinase and ARF-GEF PIN polarity
      regulation module during diverse developmental and response programs including
      shoot patterning, root growth, phototropism, gravitropism, organogenesis, leaf
      epidermal cell indentations and fruit valve margin formation. Based on these
      findings the same theme of phosphorylated PIN sorting into differential polar
      recycling pathways for PIN polarity establishment and alteration seems to be
      employed in a context-dependent manner.

PMID- 21852756
TI  - Integrating circadian and gibberellin signaling in Arabidopsis: possible links
      between the circadian clock and the AtGID1 transcription.
AB  - The circadian clock acts as central coordinator of plant activity, and it
      regulates key traits for plant fitness such as flowering time, gas exchange,
      growth, and stress responses. In the May issue of the Proceedings of the National
      Academy of Science we describe the circadian regulation of gibberellin (GA)
      signaling, through transcriptional control of GA receptor genes (GID1a and
      GID1b). We show that, in short day photocycles, the expression of GA receptors
      oscillates in seedlings, yielding a window of strong GA activity at the end of
      the night that overlaps with the period of maximum growth. This clock-mediated
      control of GA signaling is not only crucial for the establishment of rhythmic
      patterns of growth but also affects the expression of many circadian-controlled
      genes that participate in a wide range of biological processes. Here we propose a
      possible mechanism that might operate for the transcriptional control of GID1
      expression by the circadian clock.

PMID- 21852757
TI  - Multiple roles of nitrate transport accessory protein NAR2 in plants.
AB  - Two component high affinity nitrate transport system, NAR2/NRT2, has been defined
      in several plant species. In Arabidopsis, AtNAR2.1 has a role in the targeting of
      AtNRT2.1 to the plasma membrane. The gene knock out mutant atnar2.1 lacks
      inducible high-affinity transport system (IHATS) activity, it also shows the same
      inhibition of lateral root (LR) initiation on the newly developed primary roots
      as the atnrt2.1 mutant in response to low nitrate supply. In rice, OsNAR2.1
      interacts with OsNRT2.1, OsNRT2.2 and OsNRT2.3a to provide nitrate uptake over
      high and low concentration ranges. In rice roots OsNAR2.1 and its partner NRT2s
      show some expression differences in both tissue specificity and abundance. It can
      be predicted that NAR2 plays multiple roles in addition to being an IHATS
      component in plants.

PMID- 21852758
TI  - The multifaceted function of BAK1/SERK3: plant immunity to pathogens and
      responses to insect herbivores.
AB  - Almost a decade ago BRI1-associated kinase 1 (BAK1) was identified as a co
      receptor of brassinosteroid (BR) insensitive 1 (BRI1), the receptor for BRs,
      which plays an essential role in transducing BR signaling to regulate plant
      development. BAK1 is also critical in resistance to various pathogens. BAK1
      rapidly binds to certain receptors for pathogen/microbeassociated molecular
      patterns (PAMPs/MAMPs) after the perception of pathogen elicitors and is required
      for the full elicitation of pathogen-induced defense responses, such as the
      activation of the mitogen-activated protein kinase 6 (MPK6) and production of
      reactive oxygen species. Thus, BAK1 functions in both BR signaling and PAMP
      triggered immunity (PTI). Recently BAK1 was also found to play an important role
      in mediating defense responses against an insect herbivore (Manduca sexta) of
      Nicotiana attenuata. In this interaction, BAK1 positively modulates wound- or
      herbivore feeding induced accumulation of jasmonic acid (JA) and JA-isoleucine
      (JA-Ile). This mini-review summarizes recent advances in our understanding of the
      functions of BAK1 in resistance to pathogens and herbivores.

PMID- 21852759
TI  - Arabidopsis TSPO and porphyrins metabolism: a transient signaling connection?
AB  - What goes up should come down and vice versa. Cellular homeostasis requires that
      every signaling process involving up- or down-regulation of a given pathway
      should only be transient, and returning to steady state after a signaling process
      is as vital to living cells as being able to perceive and transduce changes of
      their environment. One of the best studied responses of plant cells subjected to
      water-related stress is the transient increase of the phytohormone abscisic acid
      (ABA). The increase in active ABA regulates the expression of ABA-responsive
      genes, some of which are strictly ABA-dependent in that their expression is
      almost undetectable in absence of elevated levels of cellular ABA. Since the
      function of these proteins may only be required transiently, a regulatory
      mechanism for transcriptionally and/or post-translationally regulate their
      expression should exist. In general during stress, molecular mechanisms aimed at
      shutting down the ABA-dependent signaling, as required at some point for the
      homeostasis of the plant cell, are poorly understood. The arabidopsis TSPO
      (translocator protein)-related protein is transiently induced by abiotic stresses
      and ABA treatment. Our recent work aiming at understanding the function and
      regulation of At-TSPO yielded exciting insights into the interplay among a stress
      regulated protein, ABA responses, tetrapyrrole biosynthesis/scavenging, and
      autophagy. We discuss these findings in relation to tetrapyrroles
      metabolism/trafficking and the regulation of ABA-dependent signaling by the plant
      cell.

PMID- 21852760
TI  - Dynamics of bivalent chromatin domains upon drug induced reactivation and
      resilencing in cancer cells.
AB  - Epigenetic deregulation revealed by altered profiles of DNA methylation and
      histone modifications is a frequent event in cancer cells and results in abnormal
      patterns of gene expression. Cancer silenced genes constitute prime therapeutic
      targets and considerable progress has been made in the epigenetic
      characterization of the chromatin scenarios associated with their inactivation
      and drug induced reactivation. Despite these advances, the mechanisms involved in
      the maintenance or resetting of epigenetic states in both physiological and
      pharmacological situations are poorly known. To get insights into the dynamics of
      chromatin regulation upon drug-induced reactivation, we have investigated the
      epigenetic profiles of two chromosomal regions undergoing long range epigenetic
      silencing in colon cancer cells in time-course settings after exposure of cells
      to chromatin reactivating agents. The DNA methylation states and the balance
      between histone H3K4 methylation and H3K27 methylation marks clearly define
      groups of genes with alternative responses to therapy. We show that the expected
      epigenetic remodeling induced by the reactivating drugs, just achieves a
      transient disruption of the bivalent states, which overcome the treatment and
      restore the transcriptional silencing approximately four weeks after drug
      exposure. The interplay between DNA methylation and bivalent histone marks
      appears to configure a plastic but stable chromatin scenario that is fully
      restored in silenced genes after drug withdrawal. These data suggest that
      improvement of epigenetic therapies may be achieved by designing strategies with
      long lasting effects.

PMID- 21852761
TI  - Contemporary management of vascular Ehlers-Danlos syndrome.
AB  - PURPOSE OF REVIEW: Vascular Ehlers-Danlos syndrome (EDS) results from mutations
      in the formation of type III collagen. This leads to various potentially lethal
      complications including rupture of the arterial vessels, intestinal organs, and
      the uterus. This review summarizes recent cohort studies that have improved our
      medical and surgical management of complications associated with vascular EDS.
      RECENT FINDINGS: Vascular EDS is associated with a shortened overall survival due
      to potential complications, namely loss of connective tissue integrity in blood
      vessels and increased risk of arterial rupture. The traditional approach has been
      to treat such complications conservatively unless they are life threatening.
      There have been challenges to this treatment paradigm based on recent reports.
      Treatment with the beta blocker Celiprolol was shown in a randomized study to be
      associated with a three-fold decrease in arterial rupture in vascular EDS
      patients. Furthermore, it was shown by observational studies that elective
      surgical repair of blood vessels at risk of rupture may be safely undertaken at
      tertiary referral centers that have expertise in managing connective tissue
      disorders. Novel approaches using endovascular therapy with coil embolization
      have also been attempted with good results in the treatment of ruptured
      pseudoaneurysms, visceral aneurysms, and carotid-cavernous fistulas. SUMMARY: New
      evidence-based treatments have greatly expanded the medical and surgical
      management options for patients with EDS. These patients are best managed by
      multidisciplinary teams of interventionalists, cardiologists, and geneticists in
      tertiary centers with expertise in managing connective tissue disorders.

PMID- 21852762
TI  - Treatment and microbiology of repeated cerebrospinal fluid shunt infections in
      children.
AB  - BACKGROUND: A small group of children have second and even more cerebrospinal
      fluid (CSF) shunt infections (SIs). We sought to describe the treatment
      approaches used for, and the microbiology of, repeated SIs. METHODS: The study
      population included 31 children with second shunt infection (SI-2) among those
      undergoing initial CSF shunt placement and treatment for initial infection at
      Primary Children's Medical Center. CSF SI was defined as follows: (1) presence of
      bacteria in Gram stain and/or culture of CSF, wound, and/or pseudocyst; (2)
      visible hardware; (3) abdominal pseudocyst; or (4) presence of bacteria in a
      blood culture in children with a ventriculoatrial shunt. Infection rates were
      generated using per-patient denominators, and the concordance of organisms across
      infections was summarized. RESULTS: Of the 31 children with SI-2, most were less
      than 6 months of age at initial shunt placement (81%), male (77%), and with
      ventriculoperitoneal shunts (71%). Of total, 18 developed SI-3 and 8 developed SI
      4. Infection rates were 60% (95% confidence interval [CI]: 42%-75%, n = 18/30)
      for SI-3 and 47% (95% CI: 26%-69%, n = 8/17) for SI-4. The median time to SI-3
      was 477 days (range, 5-828) and to SI-4 it was 2137 days (range, 9-2137). Gram
      positive organisms predominated (93% of SI-2, 94% of SI-3). The majority of SI-2
      demonstrated Gram-stain concordance with both the initial (first) SI (58%, 95%
      CI: 41%-74%) and with the following (third) SI (78%, 95% CI: 55%-91%).
      CONCLUSIONS: Children with SI-2 experience high subsequent reinfection rates with
      a long time to reinfection.

PMID- 21852763
TI  - Necrotizing pneumococcal pneumonia with bronchopleural fistula among children in
      Taiwan.
AB  - BACKGROUND: Severe necrotizing pneumococcal pneumonia may progress to the
      development of bronchopleural fistula (BPF). The purpose of this study was to
      describe the clinical courses and identify risk factors for the development of
      bronchopleural fistula in children with pneumococcal pneumonia. Histopathologic
      features of children receiving surgical resections of the lung because of BPF
      were analyzed to explore the pathogenesis of destructive lung disease caused by
      Streptococcus pneumoniae. METHODS: A total of 112 cases of culture-proven
      pneumococcal pneumonia were identified between January 2001 and March 2010 at
      Chang Gung Children's Hospital. The medical charts of all cases of culture-proven
      pneumococcal pneumonia were reviewed. RESULTS: Pneumococcal pneumonia in 18
      children (18/112, 16.1%) was complicated by BPF. As compared with children
      without BPF, children with BPF had significantly lower white blood cell counts at
      admission (P = 0.03) and significantly longer durations of fever and
      hospitalization (P < 0.001). Multivariate analysis revealed that acute
      respiratory failure (odds ratio = 8.9; 95% confidence interval = 2.6-30.9; P =
      0.001) and serotype 19A infection (odds ratio = 5.0; 95% confidence interval =
      1.2-22.1; P = 0.03) were risk factors for the development of BPF. Histopathologic
      analyses were available for 12 children who underwent surgical resections of the
      lung. Coagulative necrosis with pulmonary infarction was found in 11 of the 12
      cases. CONCLUSIONS: Serotype 19A was strongly associated with BPF. Vaccines
      containing this serotype will be important for prevention.

PMID- 21852764
TI  - Linezolid and lactic acidosis: a role for lactate monitoring with long-term
      linezolid use in children.
AB  - Linezolid administration has been associated with lactic acidosis in adults;
      however, the same phenomenon has not been reported in children. Mitochondrial
      protein synthesis inhibition is a demonstrated mechanism for toxicity, which
      therefore may manifest as lactic acidosis. Three cases of linezolid-associated
      lactic acidosis in children are reported to reinforce the need for pediatric
      caregivers to be vigilant of this potential side effect.

PMID- 21852765
TI  - Activity and stability studies of verbascoside, a novel antioxidant, in dermo
      cosmetic and pharmaceutical topical formulations.
AB  - We here report the results of our investigations carried out on verbascoside, a
      phenylpropanoid glycoside known for its antioxidant, anti-inflammatory and
      photoprotective actions. Verbascoside was obtained from Buddleia davidii
      meristematic cells, obtained in turn using a sustainable biotechnology platform
      which employs an in vitro plant cell culture technology. Verbascoside was first
      investigated to assess the behaviour of the active ingredient in solution or in
      finished preparations, in view of its potential topical use, especially in skin
      protection. Stability studies were performed by HPLC, and a PCL assay was adopted
      to determine the radical scavenging activity toward superoxide anion. The high
      hydrophilic character of verbascoside, suggested in a somewhat limited range of
      possible applications, leading us to explore its derivatization to obtain the
      semi-synthetic derivative VPP, an acyl derivative of verbascoside, with an
      improved range of applications due to its lower hydrophilic profile. Alone, VPP
      revealed increased antioxidant activity, both as an active ingredient and in
      dermocosmetic preparations. Stability studies showed a greater stability of VPP
      in lipophilic vehicles, whereas the parent verbascoside proved more stable in an
      O/W emulsions. Verbascoside was also stable in suppositories, an interesting
      pharmaceutical form for possible applications in treatment of inflammation of the
      intestinal mucosa.

PMID- 21852766
TI  - Synthesis and electrophilic substitutions of novel pyrazolo[1,5-c]-1,2,4
      triazolo[4,3-a]pyrimidines.
AB  - 5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1 were used as precursors
      for the preparation of a new series of 5-aryl-8-phenylpyrazolo[1,5-c]-1,2,4-
      triazolo[4,3-a]pyrimidines 2. The reactions of 2 with certain electrophilic
      reagents gave the respective 6-substituted derivatives 3-5 rather than the 7
      isomeric products. Formylation of the key compounds 1 with ethyl formate yielded
      the formyl derivatives 6. Furthermore, boiling of compounds 1 with acetic acid
      afforded 7-acetylhydrazino-5-aryl-2-phenylpyrazolo[1,5-c]pyrimidines 7.
      Bromination of 7 yielded the dibromo- derivatives 8, while their iodination and
      nitration gave the monosubstituted derivatives 9 and 10, respectively. Also,
      treatment of 1 with boiling acetic anhydride yielded the triacetyl derivatives
      11. The structure of synthesized products was confirmed by elemental analyses,
      IR, 1H NMR and MS spectra.

PMID- 21852767
TI  - Alkaloids from Hippeastrum papilio.
AB  - Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt
      (Razadyne(r), Reminyl(r)) for the treatment of Alzheimer's disease (AD), is
      obtained from Amaryllidaceae plants, especially those belonging to the genera
      Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine
      has prompted searches for new sources of this compound, as well as other
      bioactive alkaloids for the treatment of AD. In this paper we report the
      isolation of the new alkaloid 11beta-hydroxygalanthamine, an epimer of the
      previously isolated alkaloid habranthine, which was identified using NMR
      techniques. It has been shown that 11beta-hydroxygalanthamine has an important in
      vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio
      yielded substantial quantities of galanthamine.

PMID- 21852768
TI  - Quantifying risks of preterm birth in the Arkansas Medicaid population, 2001
      2005.
AB  - OBJECTIVE: The objective of this study was to examine risks of preterm births,
      quantify the explanatory power achieved by adding medical and obstetric risk
      factors to the models and to examine temporal changes in preterm birth due to
      changes in Medicaid eligibility and the establishment of a maternal-fetal
      medicine referral system. STUDY DESIGN: The study used data from the 2001 to 2005
      linked Arkansas (AR) Medicaid claims and birth certificates of preterm and term
      singleton deliveries (N=89 459). Logistic regression modeled the association
      among gestational age, demographic characteristics and risk factors, pooled and
      separately by year. RESULT: Physiological risk factors were additive with
      demographic factors and explained more of the preterm birth <=32 weeks than later
      preterm birth. Changing eligibility requirements for Medicaid recipients and
      increasing the financial threshold from 133 to 200% of federal poverty level had
      an impact on temporal changes. The proportion of births <=32 weeks declined to
      33%, from 3.0 to 2.0. However, later preterm births declined and then increased
      in the last year. CONCLUSION: Physiological conditions are strongly associated
      with early preterm birth. Maternal behaviors and other stressors are predictive
      of later preterm birth. Unmeasured effects of poverty continue to have a role in
      preterm birth. Further examination of the referral system is needed.

PMID- 21852769
TI  - Consanguinity, prematurity, birth weight and pregnancy loss: a prospective cohort
      study at four primary health center areas of Karnataka, India.
AB  - OBJECTIVE: To determine whether consanguinity adversely influences pregnancy
      outcome in South India, where consanguinity is a common means of family property
      retention. STUDY DESIGN: Data were collected from a prospective cohort of 647
      consenting women, consecutively registered for antenatal care between 14 and 18
      weeks gestation, in Belgaum district, Karnataka in 2005. Three-generation
      pedigree charts were drawn for consanguineous participants. chi (2)-Test and
      Student's t-test were used to assess categorical and continuous data,
      respectively, using SPSS version 14. Multivariate logistic regression adjusted
      for confounding variables. RESULT: Overall, 24.1% of 601 women with singleton
      births and outcome data were consanguineous. Demographic characteristics between
      study groups were similar. Non-consanguineous couples had fewer stillbirths (2.6
      vs 6.9% P=0.017; adjusted P=0.050), miscarriages (1.8 vs 4.1%, P=0.097; adjusted
      P=0.052) and lower incidence of birth weight <2500 g (21.8 vs 29.5%, P=0.071,
      adjusted P=0.044). Gestation <37 weeks was 6.2% in both the groups. Adjusted for
      consanguinity and other potential confounders, age <20 years was protective of
      stillbirth (P=0.01), pregnancy loss (P=0.023) and preterm birth (P=0.013),
      whereas smoking (P=0.015) and poverty (P=0.003) were associated with higher rates
      of low birth weight. CONCLUSION: Consanguinity significantly increases pregnancy
      loss and birth weight <2500 g.

PMID- 21852770
TI  - Risk factors for maternal outcome in pregnancy complicated with dilated
      cardiomyopathy.
AB  - OBJECTIVE: The goal of the study was to determine risk factors for maternal
      cardiac failure in pregnancy complicated with dilated cardiomyopathy (DCM). STUDY
      DESIGN: The subjects were 29 patients diagnosed with DCM before conception or
      during the first 7 months of pregnancy. DCM was defined as left ventricle end
      diastolic dimension (LVDd)>=48 mm and/or fractional shortening (%FS)<=30% on
      echocardiography. Patients were followed until at least 1 year after delivery and
      were categorized into a poor prognosis group (n=6; death or end stage heart
      failure of New York Heart Association (NYHA) class III and IV) and a good
      prognosis group (n=23; all other cases). RESULT: DCM was initially diagnosed
      during pregnancy in 6/6 and 8/23 patients in the poor and good prognosis groups,
      respectively (P<0.005). The %FS of the first test during pregnancy was 17.5+/-6.2
      and 27.4+/-9.3% in the respective groups (P<0.005). In eight abortion cases with
      %FS 15.2+/-3.1%, %FS, cardiac function and NYHA class were maintained until 20
      months after abortion. There was no relationship between LVDd and maternal
      outcome. CONCLUSION: Onset during pregnancy and decreased %FS are risk factors
      for a poor maternal outcome in patients with DCM. Abortion prevents further
      deterioration of cardiac function in patients with a very low %FS.

PMID- 21852771
TI  - Brain oxygenation monitoring during neonatal resuscitation of very low birth
      weight infants.
AB  - OBJECTIVE: To explore if regional cerebral tissue oxygen saturation monitoring by
      near-infrared spectroscopy (NIRS) is feasible during neonatal resuscitation of
      very low birth weight (VLBW) infants after birth. STUDY DESIGN: Cerebral tissue
      oxygen saturation was measured by NIRS in 51 VLBW infants (mean gestational age:
      27.8 weeks) during the first 10 min after delivery. RESULT: A regional cerebral
      tissue oxygen saturation signal was available after a median (interquartile
      range) age of 52 (44 to 68) s. In three infants the signal was obtained after 10
      min of age. After delivery cerebral tissue oxygen saturation rose continuously
      from 37 (31 to 49) % at 1 minute of age and reached a steady state in the range
      of 61 to 84% ~7 min after birth. Percentiles of cerebral tissue oxygen saturation
      of this cohort of preterm infants are given. CONCLUSION: Cerebral tissue oxygen
      saturation monitoring is feasible during neonatal resuscitation of VLBW infants
      within the first minutes of life.

PMID- 21852772
TI  - Neonatal abstinence syndrome: transitioning methadone-treated infants from an
      inpatient to an outpatient setting.
AB  - OBJECTIVE: Each year in the US ~50 000 neonates receive inpatient pharmacotherapy
      for the treatment of neonatal abstinence syndrome (NAS). The objective of this
      study is to compare the safety and efficacy of a traditional inpatient only
      approach with a combined inpatient and outpatient methadone treatment program.
      STUDY DESIGN: Retrospective review (2007 to 2009). Infants were born to mothers
      maintained on methadone in an antenatal substance abuse program. All infants
      received methadone for NAS treatment as inpatient. Methadone weaning for the
      traditional group (75 patients) was inpatient, whereas the combined group (46
      patients) was outpatient. RESULT: Infants in the traditional and combined groups
      were similar in demographics, obstetrical risk factors, birth weight, gestational
      age (GA) and the incidence of prematurity (34 and 31%). Hospital stay was shorter
      in the combined than in the traditional group (13 vs 25 days; P<0.01). Although
      the duration of treatment was longer for infants in the combined group (37 vs 21
      days, P<0.01), the cumulative methadone dose was similar (3.6 vs 3.1 mg kg(-1),
      P=0.42). Follow-up information (at least 3 months) was available for 80% of
      infants in the traditional and 100% of infants in the combined group. All infants
      in the combined group were seen <=72 h from hospital discharge. Breastfeeding was
      more common among infants in the combined group (24 vs 8% P<0.05). Following
      discharge there were no differences between the two groups in hospital
      readmissions for NAS. Prematurity (34 to 36 weeks GA) was the only predictor for
      hospital readmission for NAS in both groups (P=0.02, OR 5). Average hospital cost
      for each infant in the combined group was $13 817 less than in the traditional
      group. CONCLUSION: A combined inpatient and outpatient methadone treatment in the
      management of NAS decreases hospital stay and substantially reduces cost.
      Additional studies are needed to evaluate the potential long-term benefits of the
      combined approach on infants and their families.

PMID- 21852773
TI  - Comparing sound measurements in the single-family room with open-unit design
      neonatal intensive care unit: the impact of equipment noise.
AB  - OBJECTIVE: To determine if measured sound levels in the occupied level 3 single
      family room (SFR) neonatal intensive care unit (NICU) will be significantly and
      perceptibly different from the occupied level 3 open-unit (OU) NICU. STUDY
      DESIGN: Case-control. Comparison of sound measurements obtained with varying
      types of respiratory support in SFR unit with measurements obtained from OU level
      3 bedside NICU. RESULT: SFR sound measurements were quieter and less loud
      compared with the open unit, except when high-frequency ventilation (HFV) was
      used. CONCLUSION: The SFR level 3 NICU is a quieter, less loud environment
      compared with the open unit level 3 Bedside NICU when the patient is supported on
      room air, high flow nasal cannula, bubble continuous positive airway pressure and
      conventional ventilation. High HFV will result in similar measurements to the
      open unit level 3 bedside NICU.

PMID- 21852774
TI  - Toll2011 at Lago di Garda: studying danger sensors by the guard towers at the
      lake.

PMID- 21852775
TI  - IDO: more than an enzyme.

PMID- 21852776
TI  - A 'Tsc, Tsc' keeps the kids quie(scen)t and holds down ROS.

PMID- 21852777
TI  - IL-17R signaling: new players get in on the Act1.

PMID- 21852778
TI  - IKKalpha takes control of canonical NF-kappaB activation.

PMID- 21852786
TI  - Deregulation of microRNAs in myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDSs) consist of a family of hematopoietic stem cell
      (HSC) disorders characterized by ineffective differentiation of hematopoietic
      progenitors, bone marrow dysplasia, genetic instability and a propensity to
      develop acute myeloid leukemia. The development of MDS is poorly understood and
      therefore, effective treatment options are limited. Recent progress has been made
      in identifying altered signaling pathways and understanding the HSC defects,
      which are thought to contribute to the pathogenesis of MDS. Several of these
      findings have implicated aberrant expression and function of microRNAs (miRNAs).
      Unique miRNA expression patterns have been identified in MDS patients and modeled
      in mice to recapitulate features of MDS. Here, we review miRNA expression
      profiles identified in MDS patients, and describe the association of miRNA
      expression with MDS subtypes and disease outcome, clinical implications of miRNAs
      in MDS and deregulation of miRNAs in mouse model systems of MDS.

PMID- 21852785
TI  - NLR functions in plant and animal immune systems: so far and yet so close.
AB  - In plants and animals, the NLR family of receptors perceives non-self and
      modified-self molecules inside host cells and mediates innate immune responses to
      microbial pathogens. Despite their similar biological functions and protein
      architecture, animal NLRs are normally activated by conserved microbe- or damage
      associated molecular patterns, whereas plant NLRs typically detect strain
      specific pathogen effectors. Plant NLRs recognize either the effector structure
      or effector-mediated modifications of host proteins. The latter indirect
      mechanism for the perception of non-self, as well as the within-species
      diversification of plant NLRs, maximize the capacity to recognize non-self
      through the use of a finite number of innate immunoreceptors. We discuss recent
      insights into NLR activation, signal initiation through the homotypic association
      of N-terminal domains and subcellular receptor dynamics in plants and compare
      those with NLR functions in animals.

PMID- 21852787
TI  - Monoclonal antibody-based therapy as a new treatment strategy in multiple
      myeloma.
AB  - The introduction of autologous stem cell transplantation combined with the
      introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors has
      significantly improved survival of multiple myeloma patients. However, ultimately
      the majority of patients will develop refractory disease, indicating the need for
      new treatment modalities. In preclinical and clinical studies, promising results
      have been obtained with several monoclonal antibodies (mAbs) targeting the
      myeloma tumor cell or the bone marrow microenvironment. The mechanisms underlying
      the therapeutic efficacy of these mAbs include direct induction of tumor cell
      apoptosis via inhibition or activation of target molecules, complement-dependent
      cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The
      capability of IMiDs to enhance ADCC and the modulation of various important
      signaling cascades in myeloma cells by both bortezomib and IMiDs forms the
      rationale to combine these novel agents with mAbs as new treatment strategies for
      myeloma patients. In this review, we will give an overview of various mAbs
      directly targeting myeloma tumor cells or indirectly via effects on the bone
      marrow microenvironment. Special focus will be on the combination of these mAbs
      with IMiDs or bortezomib.

PMID- 21852789
TI  - In the family with ubiquitin.
AB  - The Cold Spring Harbor meeting on 'The Ubiquitin Family', held in May 2011,
      brought together scientists from a wide range of fields under the umbrella of
      ubiquitin and ubiquitin-like protein structure, function and regulation.

PMID- 21852790
TI  - Signalling in space and time: systems dynamics of intracellular communication.
AB  - The second edition of the EMBO Spatial meeting took place in May 2011 in
      Engelberg, Switzerland. Although the work presented at the meeting covered a
      challengingly broad range of topics, it accomplished the rare goal of promoting
      interactions between cell biologists, neuroscientists, systems biologists and
      mathematicians, all united by a common interest in understanding how cells
      integrate signals in space and time.

PMID- 21852788
TI  - The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the
      development of therapeutics.
AB  - The amyloid cascade hypothesis, which posits that the deposition of the amyloid
      beta peptide in the brain is a central event in Alzheimer's disease pathology,
      has dominated research for the past twenty years. Several therapeutics that were
      purported to reduce amyloid-beta production or aggregation have failed in Phase
      III clinical testing, and many others are in various stages of development.
      Therefore, it is timely to review the science underpinning the amyloid cascade
      hypothesis, consider what type of clinical trials will constitute a valid test of
      this hypothesis and explore whether amyloid-beta-directed therapeutics will
      provide the medicines that are urgently needed by society for treating this
      devastating disease.

PMID- 21852791
TI  - The mRNA export factor Npl3 mediates the nuclear export of large ribosomal
      subunits.
AB  - The nuclear export of large ribonucleoparticles is complex and requires specific
      transport factors. Messenger RNAs are exported through the RNA-binding protein
      Npl3 and the interacting export receptor Mex67. Export of large ribosomal
      subunits also requires Mex67; however, in this case, Mex67 binds directly to the
      5S ribosomal RNA (rRNA) and does not require the Npl3 adaptor. Here, we have
      discovered a new function of Npl3 in mediating the export of pre-60S ribosomal
      subunit independently of Mex67. Npl3 interacts with the 25S rRNA, ribosomal and
      ribosome-associated proteins, as well as with the nuclear pore complex. Mutations
      in NPL3 lead to export defects of the large subunit and genetic interactions with
      other pre-60S export factors.

PMID- 21852792
TI  - A feast for the senses: development and function of sensory systems.
AB  - The EMBO Workshop 'Frontiers in Sensory Development' took place in May 2011 in
      Barcelona. The meeting brought together a diverse group of scientists to tackle
      the formation and function of the sensory nervous system in all its complexity.
      The discussions ranged from how signalling and transcriptional networks control
      cell identity, architecture and behaviour, to how connectivity is established and
      how such networks have evolved to generate functional diversity.

PMID- 21852793
TI  - Modulation of the immune system by UV radiation: more than just the effects of
      vitamin D?
AB  - Humans obtain most of their vitamin D through the exposure of skin to sunlight.
      The immunoregulatory properties of vitamin D have been demonstrated in studies
      showing that vitamin D deficiency is associated with poor immune function and
      increased disease susceptibility. The benefits of moderate ultraviolet (UV)
      radiation exposure and the positive latitude gradients observed for some immune
      mediated diseases may therefore reflect the activities of UV-induced vitamin D.
      Alternatively, other mediators that are induced by UV radiation may be more
      important for UV-mediated immunomodulation. Here, we compare and contrast the
      effects of UV radiation and vitamin D on immune function in immunopathological
      diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.

PMID- 21852795
TI  - Psychiatric disorders: tipping the cortical balance.

PMID- 21852794
TI  - Human dendritic cell deficiency: the missing ID?
AB  - Animal models and human in vitro systems indicate that dendritic cells (DCs) have
      a crucial role in priming naive T cells, but just how important are they in the
      intact human? Recent descriptions of human DC deficiency have begun to shed light
      on this question and to illuminate other puzzles of human DC biology, including
      their haematopoietic origin, developmental regulation and homeostatic equilibrium
      with other leukocytes. In this Review, we explore the recently described DC
      deficiency syndromes, discussing what these have taught us with regard to DC
      function in humans and the important issues that remain unsolved.

PMID- 21852796
TI  - Ageing: rescuing age-related memory loss.

PMID- 21852797
TI  - Development: microglia go pruning.

PMID- 21852799
TI  - Development: pruning the dendritic tree.

PMID- 21852798
TI  - Psychiatric disorders: down with(out) neurogenesis.

PMID- 21852801
TI  - A case of persistent fetal vasculature with atypical presentation.

PMID- 21852800
TI  - Oxytocin and vasopressin in the human brain: social neuropeptides for
      translational medicine.
AB  - The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are
      evolutionarily highly conserved mediators in the regulation of complex social
      cognition and behaviour. Recent studies have investigated the effects of OXT and
      AVP on human social interaction, the genetic mechanisms of inter-individual
      variation in social neuropeptide signalling and the actions of OXT and AVP in the
      human brain as revealed by neuroimaging. These data have advanced our
      understanding of the mechanisms by which these neuropeptides contribute to human
      social behaviour. OXT and AVP are emerging as targets for novel treatment
      approaches--particularly in synergistic combination with psychotherapy--for
      mental disorders characterized by social dysfunction, such as autism, social
      anxiety disorder, borderline personality disorder and schizophrenia.

PMID- 21852802
TI  - Comparison of patient outcomes after implantation of Visian toric implantable
      collamer lens and iris-fixated toric phakic intraocular lens.
AB  - PURPOSE: We compared visual and refractive outcomes after implantation of Visian
      toric implantable collamer lenses (toric ICLs) and iris-fixated toric pIOLs
      (toric Artisans). PATIENTS AND METHODS: A comparative retrospective analysis was
      performed. Toric ICLs were implanted into 30 eyes of 18 patients, and toric
      Artisans into 31 eyes of 22 recipients. We measured the logarithms of the minimum
      angle of resolution of uncorrected visual acuity (logMAR UCVA), logMAR of best
      spectacle-corrected corrected VA (logMAR BSCVA), MR, SE, and astigmatism (by the
      power vector method) before surgery and 1, 3, and 6 months thereafter.
      Differences between patients receiving each type of lens were compared by using a
      mixed model of repeated measures. RESULTS: Visual improvements were evident after
      operation in both groups. By comparing the attempted to the achieved SE values,
      we were able to confirm that correction of refractive error was similar in both
      groups. However, the logMAR UCVA was significantly higher in the toric ICL group
      at all postoperative time points. Although manifest cylinder power and
      astigmatism (calculated by using the power vector method) gradually decreased in
      the toric ICL group, cylinder power 1 month postoperatively increased from -2.62
      to -2.75 D; astigmatism was also increased at this time in the toric Artisan
      group. CONCLUSION: The two tested toric pIOLs were similar in terms of the
      ability to correct refractive error, as assessed 3 months postoperatively.
      However toric ICLs corrected astigmatism more rapidly and safely. Notably, the
      large difference in astigmatism level between the two groups 1 month
      postoperatively indicates that toric ICLs are more effective when used to correct
      astigmatism.

PMID- 21852803
TI  - Conjunctival pigmentation after 23-gauge microincisional vitrectomy surgery.
AB  - AIM: To investigate cases with conjunctival pigmentation originating from
      sclerotomy sites after 23-gauge microincisional vitrectomy surgery (MIVS).
      METHODS: This is a retrospective study comprised of 185 eyes from 185 consecutive
      patients who underwent 23-gauge MIVS. The authors investigated the incidence and
      the clinical factors associated with conjunctival pigmentation, including
      indication of vitrectomy and surgical procedures. RESULTS: Eight eyes (4.3%) from
      185 eyes showed conjunctival pigmentation after surgery within 7 days
      postoperatively. Light microscopic examination of excised tissue showed
      infiltration of abundant dark brownish colored melanophages with surrounding
      scattered, finely granular, melanin pigments. C3F8 gas tamponade (OR, 9.4; 95%
      CI, 1.9-44.5; P=0.005) was significantly associated with conjunctival
      pigmentation. The mean surface area (21.26+/-2.21 mm(2)) of three eyes with C3F8
      tamponade was significantly larger than that of five eyes (2.51+/-0.73 mm(2))
      without tamponade (P=0.025). Neither leakage nor hypotony was found. CONCLUSIONS:
      Intraocular melanin pigments could prolapse through the sclerotomy site and cause
      conjunctival pigmentation after 23-gauge MIVS. Thus, preoperative warning is
      necessary in patients with 23-gauge MIVS.

PMID- 21852804
TI  - Neurosensory retinal detachment due to sunitinib treatment.

PMID- 21852805
TI  - Abnormal corneal nerves in a patient with Lyme disease.

PMID- 21852806
TI  - Ocular injuries from improvised explosive devices.
AB  - PURPOSE: To document the characteristics, treatments, and anatomical and
      functional outcomes of patients with ocular trauma from improvised explosive
      devices (IEDs). METHODS: Retrospective review of ocular injuries caused by IEDs,
      admitted to our tertiary referral centre. RESULTS: In total, sixty-one eyes of
      the 39 patients with an average age of 24 years (range, 20-42 years) were
      included in the study. In total, 49 (80%) eyes of the patients had open-globe and
      12 (20%) had closed-globe injury. In eyes with open-globe injury, intraocular
      foreign body (IOFB) injury was the most frequently encountered type of injury,
      observed in 76% of eyes. Evisceration or enucleation was required as a primary
      surgical intervention in 17 (28%) of the eyes. Twenty-two (36%) eyes had no light
      perception at presentation. Patients were followed up for an average of 6 months
      (range, 4-34 months). At the last follow-up, 26 (43%) of 61 eyes had no light
      perception. Postoperative proliferative vitreoretinopathy (PVR) developed in 12
      (50%) of the 24 eyes that underwent vitreoretinal surgery, and four of these eyes
      became phthisical. There were no cases of endophthalmitis. The presence of open
      globe injury and presenting visual acuity worse than 5/200 were significantly
      associated with poor visual outcome (<5/200, P<0.05). In eyes with open-globe
      injury, the presence of an IOFB was not associated with poor visual outcome
      (P>0.05). CONCLUSION: Ocular injuries from IEDs are highly associated with severe
      ocular damage requiring extensive surgical repair or evisceration/enucleation.
      Postoperative PVR is a common cause of poor anatomical and visual outcome.

PMID- 21852807
TI  - Spectral domain optical coherence tomography findings of an iatrogenic retinal
      diamond deposit.

PMID- 21852808
TI  - Tuberculoma of the choroid masquerading as a choroidal melanoma.

PMID- 21852809
TI  - Clinical characteristics of optic neuritis in Taiwanese children.
AB  - PURPOSE: To document the etiology, clinical presentation, and visual prognosis of
      optic neuritis in Taiwanese children. METHODS: Retrospectively reviewed children
      younger than 18 years old with optic neuritis in Chang Gung Memorial Hospital and
      Chang Gung Children's Hospital from 1998 to 2009. RESULTS: There were 24 children
      (38 eyes) with optic neuritis in that period. Overall, 14 patients (58.3%) were
      female and 10 patients (41.7%) were male. In total, 14 patients (58.3%) had
      bilateral involvement, and 10 patients (41.7%) had unilateral involvement. Out of
      38 eyes, 24 (63.2%) had disc swelling. Out of 24 patients, 21 (87.5%) underwent
      intravenous steroid therapy (10 to 30 mg/kg/day) for 3-5 days, and followed by an
      oral taper. Out of 24 patients, 20 (83.3%) achieved final visual acuity (VA) of
      20/40 or better. However, a poor visual outcome (four patients) (VA<20/40) was
      correlated with pale disc at presentation (P=0.002, Pearson chi (2)-test) and age
      older than 10 years (P=0.012, Fisher's exact test). Five patients were diagnosed
      with acute disseminated encephalomyelitis (ADEM) (21%), and three patients were
      diagnosed with multiple sclerosis (MS) (12.5%). Patients with ADEM did not have a
      better visual outcome than patients with MS (P=0.643, Fisher's exact test).
      CONCLUSIONS: Visual recovery from optic neuritis was favorable in Taiwanese
      children. A poor visual outcome was correlated with pale disc at presentation and
      patients' age older than 10 years. ADEM is the most common associated systemic
      disease; MS is relatively rare.

PMID- 21852810
TI  - Nerve fiber layer irregularity after internal limiting membrane peeling, seen by
      spectral domain optical coherence tomography.

PMID- 21852811
TI  - Influence of osteopontin expression on the metastatic growth of CC531 rat
      colorectal carcinoma cells in rat liver.
AB  - Development of hepatic metastasis is responsible for most of colorectal cancer
      related deaths. Osteopontin (OPN) is a small integrin-binding N-linked
      glycoprotein, which plays a crucial role in the formation of hepatic metastasis.
      This study aimed to suppress Opn expression by an antisense-oligonucleotide
      (ASO(Opn)) to decrease liver metastasis in vivo. The effect of ASO(Opn) was
      investigated in vitro in CC531(lacZ) colorectal cancer cells in comparison to
      sense (SO) or nonsense (NSO) oligomers, by determining mRNA and protein
      expression levels, as well as cell survival. For in vivo treatment, CC531(lacZ)
      cells were intraportally inoculated into rats to compare the effects of ASO, SO
      and NSO oligomers, following prolonged subcutaneous administration by osmotic
      mini-pumps. The resulting CC531(lacZ) tumor cell load in the liver was measured
      by a beta-galactosidase assay. Proliferation of CC531(lacZ) cells in vitro was
      significantly decreased after ASO(Opn) and SO treatment (P<0.001). Liver
      metastasis development was reduced as long as ASO(Opn) was administered, but this
      effect was rapidly blunted following the end of the ASO(Opn) administration. In
      contrast, administration of the SO resulted in a tumor load reduction, which
      surprisingly surpassed the ASO(Opn) effect in vivo in terms of a long-lasting
      metastasis suppression, which was accompanied with increased survival of the
      animals. Administration of the ASO(Opn) in rats was effective in decreasing their
      liver metastasis. The short-lived effect might be extended by modifications
      suited to increase the ASOs' half-life. In addition, there was a superior anti
      metastatic effect caused by the SO, which has not been reported previously.

PMID- 21852812
TI  - Oncolytic adenovirus armed with human papillomavirus E2 gene in combination with
      radiation demonstrates synergistic enhancements of antitumor efficacy.
AB  - High-risk human papillomavirus (hr-HPV) E6 and E7 oncogenes are associated with
      resistance to radiotherapy in cervical cancer. Efforts have been taken to employ
      HPV E2, a crucial negative transcriptional modulator of HPV E6 and E7 oncogenes,
      and also an apoptosis-inducing agent, for therapeutic intervention. Despite being
      conceptually attractive, the potency and feasibility of current hr-HPV E2-based
      therapies remain limited. Here, we designed a novel recombinant adenovirus, named
      M5, with a 27-bp deletion in E1A conserved region-2 by which to realize tumor
      specific replication, and a total HPV type 16 (HPV16) E2 gene complementary DNA
      inserted into the E3 coding region. In this design, M5 exploited the adenovirus
      E3 promoters to express HPV16 E2 gene in a viral replication-dependent manner and
      preferentially silenced the hr-HPV E6 and E7 oncogenes in HPV-positive cervical
      cancer cells. In vitro and in vivo assays confirmed that M5 exhibited potent
      antitumoral efficacy. Moreover, the effects of combined treatment with M5 and
      radiation treatment resulted in synergistically enhanced potency (P<0.01). The
      increase in killing efficacy of M5 was also found in HPV-negative cervical cancer
      cells, for which the pro-apoptotic activity of HPV16 E2 was thus responsible. Our
      results indicated that the use of M5 that locally delivers HPV16 E2 to cancers
      has broad therapeutic windows and that the combination therapy with radiation for
      cervical cancer will be the more effective way of improving survival.

PMID- 21852813
TI  - A losing battle: weight regain does not restore weight loss-induced bone loss in
      postmenopausal women.
AB  - Previously, we reported significant bone mineral density (BMD) loss in
      postmenopausal women after modest weight loss. It remains unclear whether the
      magnitude of BMD change in response to weight loss is appropriate (i.e.,
      proportional to weight loss) and whether BMD is recovered with weight regain. We
      now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this
      secondary analysis were postmenopausal women randomized to placebo as part of a
      larger trial. They completed a 6-month exercise-based weight loss program and
      returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was
      performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 +/-
      5.4 years (mean +/- s.d.), 10.0 +/- 9.2 years postmenopausal, and BMI was 29.6 +/
      4.0 kg/m(2). They lost 3.9 +/- 3.5 kg during the weight loss intervention.
      During follow-up, they regained 2.9 +/- 3.9 kg. Six months of weight loss
      resulted in a significant decrease in lumbar spine (LS) (-1.7 +/- 3.5%; P =
      0.002) and hip (-0.04 +/- 3.5%; P = 0.03) BMD that was accompanied by an increase
      in a biomarker of bone resorption (serum C-terminal telopeptide of type I
      collagen, CTX: 34 +/- 54%; P = 0.08). However, weight regain was not associated
      with LS (0.05 +/- 3.8%; P = 0.15) or hip (-0.6 +/- 3.0%; P = 0.81) bone regain or
      decreased bone resorption (CTX: -3 +/- 37%; P = 0.73). The findings suggest that
      BMD lost during weight reduction may not be fully recovered with weight regain in
      hormone-deficient, postmenopausal women. Future studies are needed to identify
      effective strategies to prevent bone loss during periods of weight loss.

PMID- 21852815
TI  - Intestinal permeability is associated with visceral adiposity in healthy women.
AB  - Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates
      to key metabolic dysfunctions including insulin resistance, hepatic steatosis,
      and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and
      in experimental rodent models of gut inflammation suggest that impaired gut
      barrier function with increased leakage of gut-derived antigens may drive
      visceral lipid deposition. The aim of this study was to determine whether
      increased intestinal permeability is associated with visceral adiposity in
      healthy humans. Normal to overweight female subjects were recruited from a
      population-based cohort. Intestinal permeability was assessed using the ratio of
      urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n =
      67), we found a positive correlation between waist circumference and S/M
      excretion within a time frame of urine collection consistent with permeability of
      the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These
      results were followed up in study 2 (n = 55) in which we used computed tomography
      and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat
      areas of the abdomen, liver fat content, and total body fat of the same women.
      The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P =
      0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total
      body fat. This novel finding of an association between intestinal permeability
      and visceral adiposity and liver fat content in healthy humans suggests that
      impaired gut barrier function should be further explored as a possible mediator
      of excess visceral fat accumulation and metabolic dysfunction.

PMID- 21852814
TI  - ITIH-5 expression in human adipose tissue is increased in obesity.
AB  - Adipocytes secrete many proteins that regulate metabolic functions. The gene
      inter-alpha (globulin) inhibitor H5 (ITIH-5) encodes a secreted protein and is
      known to be expressed abundantly in the placenta. However, using gene expression
      profiles data we observed high expression of ITIH-5 in adipose tissue. The aim of
      this study was to test the hypothesis that ITIH-5 is strongly expressed in human
      adipocytes and adipose tissue, and is related to obesity and clinical metabolic
      variables. ITIH-5 adipose tissue mRNA expression was analyzed with DNA microarray
      and real-time PCR, and its association with clinical variables was examined. ITIH
      5 protein expression was analyzed using western blot. ITIH-5 mRNA expression was
      abundant in human adipose tissue, adipocytes, and placenta, and higher in
      subcutaneous (sc) compared to omental adipose tissue (P < 0.0001). ITIH-5 mRNA
      and protein expression in sc adipose tissue were higher in obese compared to lean
      subjects (P < 0.0001 and P < 0.001, respectively). ITIH-5 mRNA expression was
      reduced after diet-induced weight loss (P < 0.0001). ITIH-5 mRNA expression was
      associated with anthropometry and clinical metabolic variables. In conclusion,
      ITIH-5 is highly expressed in sc adipose tissue, increased in obesity, down
      regulated after weight loss, and associated with measures of body size and
      metabolism. Together, this indicates that ITIH-5 merits further investigation as
      a regulator of human metabolism.

PMID- 21852816
TI  - 1,2-Dichloroethane.

PMID- 21852817
TI  - 1,2-Dibromo-3-chloropropane.

PMID- 21852818
TI  - 1,2-Dibromoethane.

PMID- 21852819
TI  - 1,3-Dichloropropene (technical grade).

PMID- 21852820
TI  - Diepoxybutane.

PMID- 21852821
TI  - Diesel exhaust particulates.

PMID- 21852822
TI  - Di(2-ethylhexyl) phthalate.

PMID- 21852823
TI  - Diethylstilbestrol.

PMID- 21852824
TI  - Diethyl sulfate.

PMID- 21852825
TI  - Diglycidyl resorcinol ether.

PMID- 21852826
TI  - 3,3'-Dimethoxybenzidine and dyes metabolized to 3,3'-dimethoxybenzidine: 3,3'
      dimethoxybenzidine.

PMID- 21852827
TI  - Dyes metabolized to 3,3'-dimethoxybenzidine (3,3'-dimethoxybenzidine dye class).

PMID- 21852828
TI  - 4-Dimethylaminoazobenzene.

PMID- 21852829
TI  - 3,3'-Dimethylbenzidine and dyes metabolized to 3,3'-dimethylbenzidine: 3,3'
      dimethylbenzidine.

PMID- 21852830
TI  - Dyes metabolized to 3,3'-dimethylbenzidine (3,3'-dimethylbenzidine dye class).

PMID- 21852831
TI  - Dimethylcarbamoyl chloride.

PMID- 21852832
TI  - 1,4-Dioxane.

PMID- 21852833
TI  - Disperse blue 1.

PMID- 21852834
TI  - Epichlorohydrin.

PMID- 21852835
TI  - Erionite.

PMID- 21852836
TI  - Estrogens, steroidal.

PMID- 21852837
TI  - Ethylene oxide.

PMID- 21852838
TI  - Ethylene thiourea.

PMID- 21852839
TI  - Ethyl methanesulfonate.

PMID- 21852840
TI  - Furan.

PMID- 21852841
TI  - Glycidol.

PMID- 21852842
TI  - Hepatitis B virus.

PMID- 21852843
TI  - Hepatitis C virus.

PMID- 21852844
TI  - Heterocyclic amines (Selected): 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2
      amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo[4,5
      f]quinoline, 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine.

PMID- 21852845
TI  - Hexachlorobenzene.

PMID- 21852846
TI  - Hexachloroethane.

PMID- 21852847
TI  - Hexamethylphosphoramide.

PMID- 21852848
TI  - Human papillomaviruses: some genital-mucosal types.

PMID- 21852849
TI  - Hydrazine and hydrazine sulfate.

PMID- 21852850
TI  - Hydrazobenzene.

PMID- 21852851
TI  - Ionizing radiation: x-radiation and gamma radiation.

PMID- 21852852
TI  - Ionizing radiation: neutrons.

PMID- 21852853
TI  - Ionizing radiation: radon.

PMID- 21852854
TI  - Ionizing radiation: thorium dioxide.

PMID- 21852855
TI  - Iron dextran complex.

PMID- 21852856
TI  - Isoprene.

PMID- 21852857
TI  - Kepone.

PMID- 21852858
TI  - Lead and lead compounds.

PMID- 21852859
TI  - Lindane, hexachlorocyclohexane (technical grade), and other hexachlorocyclohexane
      isomers.

PMID- 21852860
TI  - Treatment of childhood absence epilepsy-an evidence-based answer at last!

PMID- 21852861
TI  - Peri-Ictal Cardiac and Respiratory Disturbances in Epilepsy: Incidental Finding
      or Culprit of SUDEP.

PMID- 21852862
TI  - This is your brain on drugs: predicting anticonvulsant effect using transcranial
      stimulation.

PMID- 21852863
TI  - Tangled roots: digging deeper into astrocyte or interneuron dysfunction in
      temporal lobe epilepsy.

PMID- 21852864
TI  - Febrile seizures research is really heating up!

PMID- 21852865
TI  - Pyramidal Neuron Axon Initial Segment Dysregulation in Nav beta1 Subunit
      Epilepsy: A Tip of the Iceberg.

PMID- 21852866
TI  - The Devil Is in the Details: Not All AED-Associated Major Congenital
      Malformations Are Equal.

PMID- 21852867
TI  - Regulation or rising cream?

PMID- 21852868
TI  - How dangerous is epilepsy?

PMID- 21852869
TI  - Generalized Postictal EEG Background Suppression: A Marker of SUDEP Risk.

PMID- 21852870
TI  - The fat is in the fire: ketogenic diet for refractory status epilepticus.

PMID- 21852871
TI  - Anxiety disorders in epilepsy: the forgotten psychiatric comorbidity.

PMID- 21852872
TI  - Chloride's Exciting Role in Neonatal Seizures Suggests Novel Therapeutic
      Approach.

PMID- 21852873
TI  - Going viral: modeling limbic infection and seizure susceptibility.

PMID- 21852874
TI  - Combining Ubiquitin Deficiency and GABA-Mediated Inhibition Equals Seizures?

PMID- 21852875
TI  - Is depression a risk factor of worse response to therapy in epilepsy?

PMID- 21852876
TI  - Interpreting seizure counts after temporal lobectomy: not just one-two-three.

PMID- 21852877
TI  - Brand spanking? The presumptive risks of generic antiepileptic drugs.

PMID- 21852878
TI  - A persistent little current with a big impact on epileptic firing.

PMID- 21852879
TI  - Rapamycin for treatment of epilepsy: antiseizure, antiepileptogenic, both, or
      neither?

PMID- 21852880
TI  - Galanin receptors modulate seizures.

PMID- 21852881
TI  - To test our guess that breast is best: anticonvulsants and breastfeeding.

PMID- 21852882
TI  - Stopping seizures with carbon dioxide.

PMID- 21852883
TI  - Vaccination and the onset of dravet syndrome.

PMID- 21852884
TI  - Sensing the body electric: biomarkers of epileptic brain.

PMID- 21852885
TI  - Should I stay or should I go?

PMID- 21852886
TI  - Status epilepticus presenting as new-onset seizures in children.

PMID- 21852887
TI  - Sub-Optimal Choice by Pigeons: Failure to Support The Allais Paradox.
AB  - Pigeons show a preference for an alternative that provides them with
      discriminative stimuli (sometimes a stimulus that predicts reinforcement and at
      other times a stimulus that predicts the absence of reinforcement) over an
      alternative that provides them with non discriminative stimuli, even if the non
      discriminative stimulus alternative is associated with 2.5 times as much
      reinforcement (Stagner & Zentall, 1910). In Experiment 1 we found that the delay
      to reinforcement associated with the non discriminative stimuli could be reduced
      by almost one half before the pigeons were indifferent between the two
      alternatives. In Experiment 2 we tested the hypothesis that the preference for
      the discriminative stimulus alternative resulted from the fact that, like humans,
      the pigeons were attracted by the stimulus that consistently predicted
      reinforcement (the Allais paradox). When the probability of reinforcement
      associated with the discriminative stimulus that predicted reinforcement was
      reduced from 100% to 80% the pigeons still showed a strong preference for the
      discriminative stimulus alternative. Thus, under these conditions, the Allais
      paradox cannot account for the sub-optimal choice behavior shown by pigeons.
      Instead we propose that sub-optimal choice results from positive contrast between
      the low expectation of reinforcement associated with the discriminative stimulus
      alternative and the much higher obtained reinforcement when the stimulus
      associated with reinforcement appears. We propose that similar processes can
      account for sub-optimal gambling behavior by humans.

PMID- 21852888
TI  - Methodological Considerations in Studying Centenarians: Lessons Learned From the
      Georgia Centenarian Studies.

PMID- 21852889
TI  - Complicated grief treatment: the theory, practice and outcomes.
AB  - Many people resist the notion that grief could be considered a mental disorder,
      but the depth of some bereaved people's distress can mean they experience very
      great difficulty in progressing through the natural healing process. This article
      outlines an attachment theory perspective on the concept of complicated grief and
      a research-validated treatment (complicated grief therapy) that has been found to
      be effective in helping people address impediments that keep them from
      integrating the new reality of their lives.

PMID- 21852890
TI  - Positive Emotions Speed Recovery from the Cardiovascular Sequelae of Negative
      Emotions.
AB  - Two studies tested the hypothesis that certain positive emotions speed recovery
      from the cardiovascular sequelae of negative emotions. In Study 1, 60 subjects
      (Ss) viewed an initial fear-eliciting film, and were randomly assigned to view a
      secondary film that elicited: (a) contentment; (b) amusement; (c) neutrality; or
      (d) sadness. Compared to Ss who viewed the neutral and sad secondary films, those
      who viewed the positive films exhibited more rapid returns to pre-film levels of
      cardiovascular activation. In Study 2, 72 Ss viewed a film known to elicit
      sadness. Fifty Ss spontaneously smiled at least once while viewing this film.
      Compared to Ss who did not smile, those who smiled exhibited more rapid returns
      to pre-film levels of cardiovascular activation. We discuss these findings in
      terms of emotion theory and possible health-promoting functions of positive
      emotions.

PMID- 21852891
TI  - Positive emotions broaden the scope of attention and thought-action repertoires.
AB  - The broaden-and-build theory (Fredrickson, 1998, 2001) hypothesises that positive
      emotions broaden the scope of attention and thought-action repertoires. Two
      experiments with 104 college students tested these hypotheses. In each,
      participants viewed a film that elicited (a) amusement, (b) contentment, (c)
      neutrality, (d) anger, or (e) anxiety. Scope of attention was assessed using a
      global-local visual processing task (Experiment 1) and thought-action repertoires
      were assessed using a Twenty Statements Test (Experiment 2). Compared to a
      neutral state, positive emotions broadened the scope of attention in Experiment 1
      and thought-action repertoires in Experiment 2. In Experiment 2, negative
      emotions, relative to a neutral state, narrowed thought-action repertoires.
      Implications for promoting emotional well-being and physical health are
      discussed.

PMID- 21852892
TI  - Event-Based Modeling of Driver Yielding Behavior at Unsignalized Crosswalks.
AB  - This research explores factors associated with driver yielding behavior at
      unsignalized pedestrian crossings and develops predictive models for yielding
      using logistic regression. It considers the effect of variables describing driver
      attributes, pedestrian characteristics and concurrent conditions at the crosswalk
      on the yield response. Special consideration is given to 'vehicle dynamics
      constraints' that form a threshold for the potential to yield. Similarities are
      identified to driver reaction in response to the 'amber' indication at a
      signalized intersection. The logit models were developed from data collected at
      two unsignalized mid-block crosswalks in North Carolina. The data include
      'before' and 'after' observations of two pedestrian safety treatments, an in
      street pedestrian crossing sign and pedestrian-actuated in-roadway warning
      lights.The analysis suggests that drivers are more likely to yield to assertive
      pedestrians who walk briskly in their approach to the crosswalk. In turn, the
      yield probability is reduced with higher speeds, deceleration rates and if
      vehicles are traveling in platoons. The treatment effects proved to be
      significant and increased the propensity of drivers to yield, but their
      effectiveness may be dependent on whether the pedestrian activates the
      treatment.The results of this research provide new insights on the complex
      interaction of pedestrians and vehicles at unsignalized intersections and have
      implications for future work towards predictive models for driver yielding
      behavior. The developed logit models can provide the basis for representing
      driver yielding behavior in a microsimulation modeling environment.

PMID- 21852893
TI  - Self-separated PZT thick films with bulk-like piezoelectric and electromechanical
      properties.
AB  - Self-separated Pb(Zr(0.52)Ti(0.48))O(3) (PZT) films were processed by a
      hydrothermal deposition and a rapid thermal separation method, followed by a sol
      gel filling and sintering process. The films possess excellent piezoelectric and
      electromechanical properties close to those of bulk material. The maximum remnant
      polarization is over 30 MUC/cm(2) and the electromechanical coupling factor
      (k(t)) reaches as high as 0.52. The unique microstructure characteristics of the
      PZT films, such as their highly dense structure, columnar grains, well-connected
      grain boundaries, and well-dispersed nanopores, could all contribute to the
      enhanced piezoelectric and electromechanical properties.

PMID- 21852895
TI  - FERROCHELATASE: THE CONVERGENCE OF THE PORPHYRIN BIOSYNTHESIS AND IRON TRANSPORT
      PATHWAYS.
AB  - Ferrochelatase (also known as PPIX ferrochelatase; Enzyme Commission number
      4.9.9.1.1) catalyzes the insertion of ferrous iron into PPIX to form heme. This
      reaction unites the biochemically synchronized pathways of porphyrin synthesis
      and iron transport in nearly all living organisms. The ferrochelatases are an
      evolutionarily diverse family of enzymes with no more than six active site
      residues known to be perfectly conserved. The availability of over thirty
      different crystal structures, including many with bound metal ions or porphyrins,
      has added tremendously to our understanding of ferrochelatase structure and
      function. It is generally believed that ferrous iron is directly channeled to
      ferrochelatase in vivo, but the identity of the suspected chaperone remains
      uncertain despite much recent progress in this area. Identification of a
      conserved metal ion binding site at the base of the active site cleft may be an
      important clue as to how ferrochelatases acquire iron, and catalyze desolvation
      during transport to the catalytic site to complete heme synthesis.

PMID- 21852894
TI  - Non-congenital heart disease associated pediatric pulmonary arterial
      hypertension.
AB  - Recognition of causes of pulmonary hypertension other than congenital heart
      disease is increasing in children. Diagnosis and treatment of any underlying
      cause of pulmonary hypertension is crucial for optimal management of pulmonary
      hypertension. This article discusses the available knowledge regarding several
      disorders associated with pulmonary hypertension in children: idiopathic
      pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis,
      pulmonary veno-occlusive disease, hemoglobinopathies, hepatopulmonary syndrome,
      portopulmonary hypertension and HIV. Three classes of drugs have been extensively
      studied for the treatment of IPAH in adults: prostanoids (epoprostenol,
      treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan,
      sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil,
      tadalafil). These medications have been used in treatment of children with
      pulmonary arterial hypertension, although randomized clinical trial data is
      lacking. As pulmonary vasodilator therapy in certain diseases may be associated
      with adverse outcomes, further study of these medications is needed before
      widespread use is encouraged.

PMID- 21852896
TI  - In vitro and in vivo evaluation of folate receptor-targeting amphiphilic
      copolymer-modified liposomes loaded with docetaxel.
AB  - BACKGROUND: The purpose of this study was to develop folate-poly (PEG
      cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL)-modified freeze-dried
      liposomes for targeted chemotherapy using docetaxel as a model drug. METHODS: FA
      PEG-PCHL was synthesized and its cytotoxicity was evaluated by CCK-8 assay in
      L929. Docetaxel-loaded liposomes modified by FA-PEG-PCHL were prepared by an
      organic solvent injection method and lyophilized to obtain freeze-dried FA-PEG
      PCHL-docetaxel liposomes (FA-PDCT-L). Two carcinoma cell lines (MCF-7 and A-549
      cells) were cultured with docetaxel solution, conventional docetaxel-loaded
      liposomes, or FA-PDCT-L, and the cytotoxicity and apoptosis was evaluated for
      each preparation. The uptake of the docetaxel preparations into MCF-7 cells was
      studied by confocal laser scanning microscopy. Liquid chromatography-mass
      spectrometry was used to study the pharmacokinetics and tissue distribution
      characteristics of the preparations. RESULTS: The existence of an enlarged fixed
      aqueous layer on the surface of the liposomes was affirmed by zeta potential
      analysis. The entrapment efficiency and particle size distribution were almost
      the same as those of docetaxel-loaded liposomes. The drug release profile showed
      that the release rate was faster at higher molecular weight of the polymer.
      Compared with docetaxel solution and docetaxel-loaded liposomes, FA-PDCT-L
      demonstrated the strongest cytotoxicity against two carcinoma cell lines, the
      greatest intracellular uptake especially in the nucleus, as well as the most
      powerful apoptotic efficacy. In pharmacokinetic studies, the area under the
      plasma concentration-time curve of FA-PDCT-L was increased 3.82 and 6.23 times in
      comparison with the values for the docetaxel-loaded liposomes and docetaxel
      solution, respectively. Meanwhile, a lower concentration of docetaxel was
      observed for FA-PDCT-L in the liver and spleen, and a significantly higher
      concentration of FA-PDCT-L in tumors suggested that the presence of FA-PEG-PCHL
      on the liposomes resulted in greater accumulation of the drug in tumor tissue.
      CONCLUSION: Liposomes modified by FA-PEG-PCHL could be one of the promising
      suspensions for the delivery of antitumor drugs in cancer.

PMID- 21852897
TI  - Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands
      in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa).
AB  - The aim of our project was to study the effect of streptozotocin (STZ)-induced
      hyperglycemia on sciatic nerve morphology, blood plasma markers and
      immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End
      products), and its ligands-S100B and Carboxymethyl Lysine (CML)-advanced
      glycation endproduct (AGE) in the laboratory pig. Six months after STZ
      injections, blood plasma measurements, morphometric analysis of sciatic nerve
      fiber density, immunofluorescent distribution of potential molecular neuropathy
      contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic
      nerve levels of one of the pre-AGE and the glycolysis intermediate products
      methyl-glyoxal (MG) were performed. The results of our study revealed that STZ
      injected animals displayed elevated levels of plasma glucose, gamma glutamyl
      transferase (GGT) and triglycerides. The sciatic nerve of STZ-injected pigs
      revealed significantly lower numbers of small-diameter myelinated fibers, higher
      immunoreactivity for RAGE and S100B and increased levels of MG as compared to
      control animals. Our results correspond to clinical findings in human patients
      with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the
      domestic pig may be a suitable large animal model for the study of mechanisms
      underlying hyperglycemia-induced neurological complications in the peripheral
      nerve and may serve as a relevant model for the pre-clinical assessment of
      candidate drugs in neuropathy.

PMID- 21852898
TI  - Expression of mannose binding lectin in HIV-1-infected brain: implications for
      HIV-related neuronal damage and neuroAIDS.
AB  - Mannose binding lectin (MBL) activates complement pathway that leads to pathogen
      opsonization and phagocytosis. MBL deficiency is linked to HIV transmission and
      disease progression. We sought to determine the role of MBL in HIV encephalitis
      (HIVE) by evaluating its presence and distribution in the HIV-1-infected brain
      and by assessing its association with monocyte chemoattractant protein-1 (MCP-1)
      expression. This retrospective study utilized archived post-mortem brain tissues
      obtained from 35 individuals enrolled in a longitudinal study as part of the
      California NeuroAIDS Tissue Network. MBL, MCP-1 and brain cell markers in post
      mortem brain tissues with or without HIVE were evaluated using
      immunocytochemistry, immunofluorescence, confocal microscopy, and western blots.
      MBL was expressed in neurons, astrocytes, microglia, and oligodendrocytes of the
      frontal cortex of the HIV-1-infected brain. Overall, there were 30% to 40% more
      MBL-positive brain cells in HIVE vs non-HIVE cases (P = 0.01, paired t-test).
      Specifically, there was an increased MBL expression in the neuronal axons of HIVE
      cases. Also, western blots showed 3- to 4-fold higher levels of 78 kD MBL trimers
      in HIVE vs non-HIVE cases. This MBL-HIVE link was further confirmed by MBL
      associated higher MCP-1 expression in HIVE vs non-HIVE cases. HIV negative
      healthy individuals and normal or the gp120 transgenic mice did not show any
      differential MBL expression. Increased MBL expression in the major brain cell
      types, specifically in the neuronal axons of HIVE brain, and MBL associated
      higher MCP-1 expression in HIVE suggest that MBL could cause neuroinflammation
      and neuronal injury through MBL complement activation pathway.

PMID- 21852899
TI  - Insulin-like growth factor binding protein-3 is required for the regulation of
      rat oval cell proliferation and differentiation in the 2AAF/PHX model.
AB  - Oval cell-mediated liver regeneration is a highly complex process that involves
      the coordination of several signaling factors, chemokines and cytokines to allow
      for proper maintenance of the liver architecture. When hepatocyte proliferation
      is inhibited, an hepatic stem cell population, often referred to as "oval cells",
      is activated to aid in liver regeneration. The function of insulin-like growth
      factor binding protein-3 (IGFBP-3) during this process of oval cell activation is
      of particular interest because it is produced in liver and has been shown to
      induce migration and differentiation of other stem cell populations both in vitro
      and in vivo. Additionally, IGFBP-3 production has been linked to the transforming
      growth factor-beta (TGF-beta) superfamily, a pathway known to be induced during
      oval cell proliferation. In this study, we set out to determine whether IGFBP-3
      plays a role in oval cell proliferation, migration and differentiation during
      this specific type of regeneration. Through activation of the oval cell-mediated
      liver regeneration in a rat model, we found that IGFBP-3 is elevated in the liver
      and serum of animals during peak days of oval cell activation and proliferation.
      Furthermore, in vitro assays found that WB-344 cells, a liver stem cell line
      similar to oval cells, were induced to migrate in the presence of IGFBP-3. When
      expression of IGFBP-3 was knocked down during oval cell activation in vivo, we
      found that oval cell proliferation was increased and observed the appearance of
      numerous atypical ductular structures, which were OV-6 and Ki67-positive.
      Finally, quantitative real-time PCR analysis of liver tissue from IGFBP-3 small
      interfering RNA (siRNA) treated animals determined that expression of TGFbeta
      family members, including TGF-betaRII and Smads 2-4, were significantly
      downregulated compared to animals at day 9 post-PHx alone or animals that
      received negative control siRNA. In conclusion, IGFBP-3 may function as a potent
      chemoattractant of oval cells during specific types of liver regeneration and may
      be involved in regulating oval cell proliferation and differentiation in vivo via
      the TGF-beta pathway.

PMID- 21852900
TI  - Consensus report of the 4th International Forum for Gadolinium-Ethoxybenzyl
      Diethylenetriamine Pentaacetic Acid Magnetic Resonance Imaging.
AB  - This paper reports on issues relating to the optimal use of gadolinium
      ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd
      EOB-DTPA MR imaging) together with the generation of consensus statements from a
      working group meeting, which was held in Seoul, Korea (2010). Gd-EOB-DTPA has
      been shown to improve the detection and characterization of liver lesions, and
      the information provided by the hepatobiliary phase is proving particularly
      useful in differential diagnoses and in the characterization of small lesions
      (around 1-1.5 cm). Discussion also focused on advances in the role of organic
      anion-transporting polypeptide 8 (OATP8) transporters. Gd-EOB-DTPA is also
      emerging as a promising tool for functional analysis, enabling the calculation of
      post-surgical liver function in the remaining segments. Updates to current
      algorithms were also discussed.

PMID- 21852901
TI  - Diagnostic value of 64-slice dual-source CT coronary angiography in patients with
      atrial fibrillation: comparison with invasive coronary angiography.
AB  - OBJECTIVE: We wanted to evaluate the image quality and diagnostic value of 64
      slice dual-source computed tomography (DSCT) coronary angiography in patients
      with atrial fibrillation (Afib). MATERIALS AND METHODS: The coronary arteries of
      22 Afib patients seen on DSCT were classified into 15 segments and the imaging
      quality (excellent, good, moderate and poor) and significant stenoses (>= 50%)
      were evaluated by two radiologists who were blinded to the conventional coronary
      angiography (CAG) results. The sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) for detecting important coronary
      artery stenosis were calculated. McNemar test was used to determine any
      significant difference between DSCT and CAG, and Cohen's Kappa statistics were
      calculated for the intermodality and interobserver agreement. RESULTS: The mean
      heart rate was 89 +/- 8.3 bpm (range: 80-118 bpm). A range from 250 msec to 300
      msec within the RR interval was the optimal reconstruction interval for the
      patients with Afib. The respective overall sensitivity, specificity, PPV and NPV
      values were 74%, 97%, 81% and 96% for reader 1 and 72%, 98%, 85% and 96% for
      reader 2. No significant difference between DSCT and CAG was found for detecting
      a significant stenosis (reader 1, p = 1.0; reader 2, p = 0.727). Cohen's Kappa
      statistics demonstrated good intermodality and interobserver agreement.
      CONCLUSION: 64-slice DSCT coronary angiography provides good image quality in
      patients with atrial fibrillation without the need for controlling the heart
      rate. DSCT can be used for ruling out significant stenosis in patients with
      atrial fibrillation with its high NPV for detecting in important stenosis.

PMID- 21852902
TI  - The adverse events and hemodynamic effects of adenosine-based cardiac MRI.
AB  - OBJECTIVE: We wanted to prospectively assess the adverse events and hemodynamic
      effects associated with an intravenous adenosine infusion in patients with
      suspected or known coronary artery disease and who were undergoing cardiac MRI.
      MATERIALS AND METHODS: One hundred and sixty-eight patients (64 +/- 9 years)
      received adenosine (140 ug/kg/min) during cardiac MRI. Before and during the
      administration, the heart rate, systemic blood pressure, and oxygen saturation
      were monitored using a MRI-compatible system. We documented any signs and
      symptoms of potential adverse events. RESULTS: In total, 47 out of 168 patients
      (28%) experienced adverse effects, which were mostly mild or moderate. In 13
      patients (8%), the adenosine infusion was discontinued due to intolerable dyspnea
      or chest pain. No high grade atrioventricular block, bronchospasm or other life
      threatening adverse events occurred. The hemodynamic measurements showed a
      significant increase in the heart rate during adenosine infusion (69.3 +/- 11.7
      versus 82.4 +/- 13.0 beats/min, respectively; p < 0.001). A significant but
      clinically irrelevant increase in oxygen saturation occurred during adenosine
      infusion (96 +/- 1.9% versus 97 +/- 1.3%, respectively; p < 0.001). The blood
      pressure did not significantly change during adenosine infusion (systolic: 142.8
      +/- 24.0 versus 140.9 +/- 25.7 mmHg; diastolic: 80.2 +/- 12.5 mmHg versus 78.9 +/
      15.6, respectively). CONCLUSION: This study confirms the safety of adenosine
      infusion during cardiac MRI. A considerable proportion of all patients will
      experience minor adverse effects and some patients will not tolerate adenosine
      infusion. However, all adverse events can be successfully managed by a
      radiologist. The increased heart rate during adenosine infusion highlights the
      need to individually adjust the settings according to the patient, e.g., the
      number of slices of myocardial perfusion imaging.

PMID- 21852903
TI  - Segmental difference of the hepatic fibrosis from chronic viral hepatitis due to
      hepatitis B versus C virus infection: comparison using dual contrast material
      enhanced MRI.
AB  - OBJECTIVE: We wanted to identify the geographic differences in hepatic fibrosis
      and their associations with the atrophy-hypertrophy complex in patients with
      chronic viral hepatitis using the dual-contrast material-enhanced MRI (DC-MRI)
      with gadopentetate dimeglumine and ferucarbotran. MATERIALS AND METHODS: Patients
      with chronic C (n = 22) and B-viral hepatitis (n = 35) were enrolled for
      determining the subjective grade of fibrosis (the extent and thickness of
      fibrotic reticulations) in the right lobe (RL), the caudate lobe (CL), the medial
      segment (MS) and the lateral segment (LS) of the liver, with using a 5-grade
      scale, on the gradient echo T2(*)-weighted images of DC-MRI. The fibrosis grades
      of different segments were compared using the Kruskal-Wallis test followed by
      post-hoc analysis to establish the segment-by-segment differences. The incidences
      of two pre-established morphologic signs of cirrhosis were also compared with
      each other between the two groups of patients. RESULTS: There were significant
      intersegmental differences in fibrosis grades of the C-viral group (p = 0.005),
      and the CL showed lower fibrosis grades as compared with the grades of the RL and
      MS, whereas all lobes were similarly affected in the B-viral group (p = 0.221).
      The presence of a right posterior hepatic notch was significantly higher in the
      patients with intersegmental differences of fibrosis between the RL and the CL
      (19 out of 25, 76%) than those without such differences (6 out of 32, 19%) (p <
      0.001). An expanded gallbladder fossa showed no significant relationship (p =
      0.327) with the segmental difference of the fibrosis grades between the LS and
      the MS. CONCLUSION: The relative lack of fibrosis in the CL with more advanced
      fibrosis in the RL can be a distinguishing feature to differentiate chronic C
      viral hepatitis from chronic B-viral hepatitis and this is closely related to the
      presence of a right posterior hepatic notch.

PMID- 21852904
TI  - Differentiating focal eosinophilic infiltration from metastasis in the liver with
      gadoxetic acid-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: To determine the most useful findings of gadoxetic acid-enhanced 3.0
      Tesla (T) MRI for differentiating focal eosinophilic infiltration (FEI) from
      hepatic metastasis with verification of their usefulness. MATERIALS AND METHODS:
      Pathologically or clinically proven 39 FEIs from 25 patients and 79 hepatic
      metastases from 51 patients were included in the study. Gadoxetic acid-enhanced
      3.0T MRI was performed in all cancer patients. Size differences measured between
      T2-weighted and hepatobiliary-phase images for lesions > 1 cm and morphologic
      findings (margin, shape, signal intensity on T1- and T2-weighted images,
      enhancement pattern on dynamic images, and target appearance on hepatobiliary
      phase images) were compared between two groups via Student's t test as well as
      univariate and multivariate analyses. Diagnostic predictive values of two
      observers for differentiating two groups were assessed before (session 1) and
      after (session 2) recognition of results. RESULTS: Mean size difference (2.1 mm)
      in FEIs between the two images was significantly greater than for metastases (0.7
      mm) (p < 0.05). An ill-defined margin and isointensity on T1-weighted images were
      independently significant morphologic findings (p < 0.05) for differentiating the
      two groups. All observers achieved a higher diagnostic accuracy in session 2 (97%
      and 98%) than session 1 (92% and 89%) with statistical significance in observer 2
      (p < 0.05). All observers had significantly higher sensitivities (95%) and
      negative predictive values (NPVs) (98%) in session 2 than in session 1
      (sensitivity, 74% in two observers; NPV, 89% and 88%) (p < 0.05). CONCLUSION:
      With the size change, an ill-defined margin and isointensity on T1-weighted
      images are the most useful findings for differentiating FEI from hepatic
      metastasis on gadoxetic acid-enhanced 3.0T MRI.

PMID- 21852905
TI  - Evaluation of portal venous velocity with Doppler ultrasound in patients with
      nonalcoholic fatty liver disease.
AB  - PURPOSE: We examined the relationship between portal venous velocity and hepatic
      abdominal fat in patients with nonalcoholic fatty liver disease (NAFLD), using
      spectral Doppler ultrasonography (US) and magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: In this prospective study, 35 patients with NAFLD and 29
      normal healthy adults (control group) underwent portal Doppler US. The severity
      of hepatic steatosis in patients with NAFLD was assessed by MRI through chemical
      shift imaging, using a modification of the Dixon method. Abdominal (intra
      abdominal and subcutaneous) fat was measured by MRI. RESULTS: The difference in
      portal venous velocity between the patients with NAFLD and the control group was
      significant (p < 0.0001). There was no correlation between the degree of
      abdominal or hepatic fat and portal venous velocity (p > 0.05). There were strong
      correlations between the hepatic fat fraction and subcutaneous adiposity (p <
      0.0001), intraperitoneal fat accumulation (p = 0.017), and retroperitoneal fat
      accumulation (p < 0.0001). CONCLUSION: Our findings suggest that patients with
      NAFLD have lower portal venous velocities than normal healthy subjects.

PMID- 21852906
TI  - The serum CA-125 concentration data assists in evaluating CT imaging information
      when used to differentiate borderline ovarian tumor from malignant epithelial
      ovarian tumors.
AB  - OBJECTIVE: We wanted to evaluate the diagnostic value of serum CA-125
      concentration, when used in combination with the preoperative contrast-enhanced
      CT results, to differentiate borderline ovarian tumors (BOTs) from stage I
      malignant epithelial ovarian tumors (MEOTs). MATERIALS AND METHODS: Ninety-eight
      masses (46 BOTs and 52 stage I MEOTs) from 87 consecutive patients (49 with BOTs
      and 38 with stage I MEOTs) who had undergone preoperative contrast-enhanced
      computed tomography (CT) and surgical staging were evaluated retrospectively and
      independently by two radiologists. The preoperative serum CA-125 concentration
      was measured in all patients. The utility of analyzing serum CA-125 concentration
      in combination with the CT results was evaluated by receiver operating
      characteristic (ROC) curve analysis. RESULTS: An irregular tumor surface and
      lymphadenopathy were predictive of a MEOT. ROC analysis showed that the
      combination of CT data and the serum CA-125 level resulted in a higher diagnostic
      performance than did using the CT alone for differentiating BOTs from MEOTs. The
      areas under the curves (AUCs) without and with the use of the serum CA-125 level
      data were 0.67 (95% confidence interval [CI]: 0.57-0.77) and 0.78 (95% CI: 0.68
      0.85), respectively, for reader 1 (p = 0.029) and 0.71 (95% CI: 0.61-0.80) and
      0.81 (95% CI: 0.72-0.89), respectively, for reader 2 (p = 0.009). CONCLUSION: The
      serum CA-125 concentration is of additional diagnostic value when used in
      conjunction with the CT imaging results for differentiating BOTs from MEOTs.

PMID- 21852907
TI  - Assessment of cortical visual impairment in infants with periventricular
      leukomalacia: a pilot event-related FMRI study.
AB  - OBJECTIVE: We wanted to investigate the usefulness of event-related (ER)
      functional MRI (fMRI) for the assessment of cortical visual impairment in infants
      with periventricular leukomalacia (PVL). MATERIALS AND METHODS: FMRI data were
      collected from 24 infants who suffered from PVL and from 12 age-matched normal
      controls. Slow ER fMRI was performed using a 3.0T MR scanner while visual stimuli
      were being presented. Data analysis was performed using Statistical Parametric
      Mapping software (SPM2), the SPM toolbox MarsBar was used to analyze the region
      of interest data, and the time to peak (TTP) of hemodynamic response functions
      (HRFs) was estimated for the surviving voxels. The number of activated voxels and
      the TTP values of HRFs were compared. Pearson correlation analysis was performed
      to compare visual impairment evaluated by using Teller Acuity Cards (TAC) with
      the number of activated voxels in the occipital lobes in all patients. RESULTS:
      In all 12 control infants, the blood oxygenation level-dependent (BOLD) signal
      was negative and the maximum response was located in the anterior and superior
      part of the calcarine fissure, and this might correspond to the anterior region
      of the primary visual cortex (PVC). In contrast, for the 24 cases of PVL, there
      were no activated pixels in the PVC in four subjects, small and weak activations
      in six subjects, deviated activations in seven subjects and both small and
      deviated activations in three subjects. The number of active voxels in the
      occipital lobe was significantly correlated with the TAC-evaluated visual
      impairment (p < 0.001). The mean TTP of the HRFs was significantly delayed in the
      cases of PVL as compared with that of the normal controls. CONCLUSION:
      Determining the characteristics of both the BOLD response and the ER fMRI
      activation may play an important role in the cortical visual assessment of
      infants with PVL.

PMID- 21852908
TI  - Nonvariceal upper gastrointestinal bleeding: the usefulness of rotational
      angiography after endoscopic marking with a metallic clip.
AB  - OBJECTIVE: We wanted to assess the usefulness of rotational angiography after
      endoscopic marking with a metallic clip in upper gastrointestinal bleeding
      patients with no extravasation of contrast medium on conventional angiography.
      MATERIALS AND METHODS: In 16 patients (mean age, 59.4 years) with acute bleeding
      ulcers (13 gastric ulcers, 2 duodenal ulcers, 1 malignant ulcer), a metallic clip
      was placed via gastroscopy and this had been preceded by routine endoscopic
      treatment. The metallic clip was placed in the fibrous edge of the ulcer adjacent
      to the bleeding point. All patients had negative results from their angiographic
      studies. To localize the bleeding focus, rotational angiography and high pressure
      angiography as close as possible to the clip were used. RESULTS: Of the 16
      patients, seven (44%) had positive results after high pressure angiography as
      close as possible to the clip and they underwent transcatheter arterial
      embolization (TAE) with microcoils. Nine patients without extravasation of
      contrast medium underwent TAE with microcoils as close as possible to the clip.
      The bleeding was stopped initially in all patients after treatment of the feeding
      artery. Two patients experienced a repeat episode of bleeding two days later. Of
      the two patients, one had subtle oozing from the ulcer margin and that patient
      underwent endoscopic treatment. One patient with malignant ulcer died due to
      disseminated intravascular coagulation one month after embolization. Complete
      clinical success was achieved in 14 of 16 (88%) patients. Delayed bleeding or
      major/minor complications were not noted. CONCLUSION: Rotational angiography
      after marking with a metallic clip helps to localize accurately the bleeding
      focus and thus to embolize the vessel correctly.

PMID- 21852909
TI  - Early results of endovenous ablation with a 980-nm diode laser for an incompetent
      vein of Giacomini.
AB  - OBJECTIVE: We wanted to evaluate the effectiveness of endovenous ablation of the
      incompetent vein of Giacomini using a 980-nm diode laser. MATERIALS AND METHODS:
      A total of 18 patients (18 limbs, 4%) had the incompetent vein of Giacomini.
      Retrograde reflux originating from the great saphenous vein was noted in sixteen
      limbs and paradoxical diastolic anterograde reflux from the saphenopopliteal
      junction was observed in two limbs. After tumescent anesthesia, laser ablation
      using a 980-nm wavelength laser fiber was performed under ultrasound and/or
      fluoroscopic guidance. Patients were evaluated clinically and with duplex
      ultrasound at one week and at one, three, six and twelve months after laser
      ablation for the technical and clinical success. RESULTS: In the 18 limbs, the
      technical success rate was 100%. Continued closure of the vein of Giacomini was
      seen in 18 of 18 limbs after one month, in 12 of 12 limbs after three and six
      months and in six of six limbs after twelve months. No recanalization of the vein
      and no major complications occurred. CONCLUSION: Endovenous laser ablation with a
      980-nm wavelength is an effective and safe procedure for treating an incompetent
      vein of Giacomini.

PMID- 21852910
TI  - MRI findings of rectal submucosal tumors.
AB  - Rectal submucosal lesions encompass a wide variety of benign and malignant tumors
      involving the rectum. With optical colonoscopy, any mass-like protrusion covered
      by normal mucosa, whether the underlying process is intramural or extramural in
      origin, may be reported as a submucosal lesion. Whereas the assessment of
      submucosal lesions may be limited with performing optical colonoscopy, cross
      sectional imaging such as CT, transrectal ultrasonography and MRI allows the
      evaluation of perirectal tissues and pelvic organs in addition to the entire
      thickness of the rectum, and so this is advantageous for the assessment of rectal
      submucosal tumors. Among these, MRI is the best investigative modality for soft
      tissue characterization. Therefore, knowledge of the MRI features of rectal
      submucosal tumors can help achieve accurate preoperative diagnoses and facilitate
      the appropriate management.

PMID- 21852911
TI  - Reversal in the diameter of the superior ophthalmic vein after an epidural blood
      patch in a case of spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension (SIH) is caused by single or multiple
      cerebrospinal fluid (CSF) leaks in the spine with the prototypical symptom of
      postural headache. One of the characteristic MRI features in SIH is intracranial
      venous engorgement. This report presents a case of SIH with engorgement of the
      bilateral superior ophthalmic veins (SOVs) which resume their normal diameters by
      the third day of successful epidural blood patches (EBPs). We define this
      phenomenon as the "reversal of the SOV" sign.

PMID- 21852912
TI  - Acute retropharyngeal calcific tendinitis in an unusual location: a case report
      in a patient with rheumatoid arthritis and atlantoaxial subluxation.
AB  - Retropharyngeal calcific tendinitis is defined as inflammation of the longus
      colli muscle and is caused by the deposition of calcium hydroxyapatite crystals,
      which usually involves the superior oblique fibers of the longus colli muscle
      from C1-3. Diagnosis is usually made by detecting amorphous calcification and
      prevertebral soft tissue swelling on radiograph, CT or MRI. In this report, we
      introduce a case of this disease which was misdiagnosed as a retropharyngeal
      tuberculous abscess, or a muscle strain of the ongus colli muscle. No
      calcifications were visible along the vertical fibers of the longus colli muscle.
      The lesion was located anterior to the C4-5 disc, in a rheumatoid arthritis
      patient with atlantoaxial subluxation. Calcific tendinitis of the longus colli
      muscle at this location in a rheumatoid arthritis patient has not been reported
      in the English literature.

PMID- 21852913
TI  - Imaging findings of localized lymphoid hyperplasia of the pancreas: a case
      report.
AB  - We report here on a case of localized lymphoid hyperplasia of the pancreas in a
      70-year-old man which manifested as double lesions (uncinate process and tail) in
      the organ. The lesions were incidentally detected as hypoechoic lesions on
      ultrasonography and they appeared as delayed enhancing lesions on the contrast
      enhanced dynamic CT and MRI. Total pancreatectomy was performed, because
      malignant tumor could not be excluded according to the preoperative imaging
      studies and the endoscopic ultrasound-guided biopsy failed. Pathology revealed
      localized lymphoid hyperplasia. The patient had an uneventful postoperative
      course. He has been alive for 18 months after surgery.

PMID- 21852914
TI  - High shear stress at the surface of enhancing plaque in the systolic phase is
      related to the symptom presentation of severe M1 stenosis.
AB  - The computational fluid dynamics methods for the limited flow rate and the small
      dimensions of an intracranial artery stenosis may help demonstrate the stroke
      mechanism in intracranial atherosclerosis. We have modeled the high wall shear
      stress (WSS) in a severe M1 stenosis. The high WSS in the systolic phase of the
      cardiac cycle was well-correlated with a thick fibrous cap atheroma with
      enhancement, as was determined using high-resolution plaque imaging techniques in
      a severe stenosis of the middle cerebral artery.

PMID- 21852916
TI  - Systematics of the Phyllognathopodidae (Copepoda, Harpacticoida): re-examination
      of Phyllognathopus viguieri (Maupas, 1892) and Parbatocamptus jochenmartensi
      Dumont and Maas, 1988, proposal of a new genus for hyllognathopus bassoti Rouch,
      1972, and description of a new species of Phyllognathopus.
AB  - The family Phyllognathopodidae (Crustacea, Copepoda, Harpacticoida) is heavily
      affected by the floating taxonomic status of the type-genus Phyllognathopus. A
      revision of the different character states displayed by members of the family is
      presented, and new phylogenetically informative characters are described,
      enlarging the analysis to the remaining genera of the family, Parbatocamptus and
      Allophyllognathopus. Phyllognathopus viguieri (Maupas, 1892) and Parbatocamptus
      jochenmartensi Dumont and Maas, 1988 are redescribed in detail, and
      Phyllognathopus inexspectatussp. n. is described from ground water in Italy. The
      new genus Neophyllognathopus is established to accommodate Phyllognathopus
      bassoti Rouch, 1972,originally collected from Long Island (Papua - New Guinea),
      and subsequently recorded also from the Bantayan Island (Philippines), and from
      the Indian subcontinent. The new genus is presently monotypic and is easily
      defined by the unique construction and morphology of leg 5 in both male and
      female, of male leg 6, and by the peculiar ornamentation of male third and fourth
      urosomites. Biogeographical and ecological considerations are presented for
      members of the family.

PMID- 21852915
TI  - MRI appearance of prostatic stromal sarcoma in a young adult.
AB  - Prostatic stromal sarcoma (PSS) is quite rare. Herein, we describe magnetic
      resonance imaging (MRI) features of a PSS identified in a 26-year-old man with
      dysuria and hematuria. MRI clearly depicted the extent and multinodular
      appearance of the tumor, which was mainly located in the central zone of the
      prostate. The tumor appeared as a heterogeneously signal-hyperintense mass with a
      pseudocapsule on T2-weighted imaging. Contrast-enhanced T1-weighted MRI showed
      necrotic portions in the gradually enhanced solid mass, and diffusion-weighted
      imaging permitted the accurate assessment of the local extent of the tumor. Thus,
      the appearance on MRI was quite different from that of adenocarcinoma of the
      prostate.

PMID- 21852917
TI  - Key to the tribes and genera of deltocephaline leafhoppers (auchenorrhyncha,
      hemiptera, cicadellidae) of pakistan.
AB  - A key with accompanying figures is provided for the 14 tribes and 35 genera of
      Deltocephalinae (Cicadellidae) from Pakistan.

PMID- 21852918
TI  - Two new species of Pterostichus Bonelli subgenus Pseudoferonina Ball (Coleoptera,
      Carabidae, Pterostichini) from the mountains of central Idaho, U.S.A.
AB  - Two new species of Pterostichus Bonelli subgenus Pseudoferonina Ball, are
      described from the mountains of central Idaho: Pterostichus bousqueti Bergdahl
      [type locality = small tributaries of South Fork of Payette River watershed, ca.
      1170 m (3840 ft), 44.0675 degrees ; -115.6822 degrees , near Lowman, Salmon River
      Mountains, Boise County, Idaho, U.S.A.] and Pterostichus lolo Bergdahl [type
      locality = Cottonwood/Orogrande Creek, ca. 870 m (2850 ft), 46.5528 degrees ; 
      115.5522 degrees , North Fork of Clearwater River watershed, Clearwater
      Mountains, near Bungalow, Clearwater County, Idaho, U.S.A.]. Males of
      Pterostichus bousqueti and Pterostichus lolo are easily distinguished from each
      other and the seven previously described Pseudoferonina species by the form of
      the median lobe of the aedeagus, and from most individuals of the other species
      of Pseudoferonina in Idaho by features of pronotal shape and macrosculpture. Both
      species appear to be obligate ripicolous hygrophiles, restricted in distribution
      primarily to the margins of small montane streams in forested areas. Widespread
      intensive stream surveys for Pseudoferonina over many years indicate the
      geographic ranges of both species are highly localized, and additional
      undescribed species may occur in Idaho.

PMID- 21852919
TI  - A revision of the spider genus Selenops Latreille, 1819 (Arachnida, Araneae,
      Selenopidae) in North America, Central America and the Caribbean.
AB  - The spider genus Selenops Latreille, 1819 occurs in both the Old World and New
      World tropics and subtropics and contains nearly half of the species in the
      family Selenopidae Simon, 1897. In this paper the members of the genus Selenops
      found in North America, Central America, and on islands of the Caribbean are
      revised, excluding Cuban endemics. No taxonomic changes are currently made to the
      species from the southwestern United States. In total, 21 new species are
      described, including Selenops arikoksp. n., Selenops chamelasp. n., Selenops
      amonasp. n., Selenops bawekasp. n., Selenops bocacanadensissp. n., Selenops
      enriquillosp. n, Selenops ixchelsp. n., Selenops huetocatlsp. n., Selenops
      kalinagosp. n., Selenops oviedosp. n., Selenops morrosp. n., Selenops deniasp.
      n., Selenops duansp. n., Selenops malinalxochitlsp. n., Selenops oricuajosp. n.,
      Selenops petenajtoysp. n., Selenops guerrerosp. n., Selenops makimakisp. n.,
      Selenops souligasp. n., Selenops wilmotorumsp. n., and Selenops wilsonisp. n. Six
      species names were synonymized: Selenops lunatus Muma, 1953 syn. n. =Selenops
      candidus Muma, 1953; Selenops tehuacanus Muma 1953 syn. n., Selenops
      galapagoensis Banks, 1902 syn. n. and Selenops vagabundus Kraus, 1955 syn. n. =
      Selenops mexicanus Keyserling, 1880; Selenops santibanezi Valdez-Mondragon, 2010
      syn. n. = Selenops nigromaculatus Keyserling, 1880; and Selenops salvadoranus
      Chamberlin, 1925 syn. n. = Selenops bifurcatus Banks, 1909. Lectotypes are
      designated for the following three species: Selenops marginalis F. O. Pickard
      Cambridge, 1900 (?), Selenops morosus Banks, 1898 (?), and Selenops mexicanus
      Keyserling, 1880 (?). The female neotype is designated for Selenops aissus
      Walckenaer, 1837. The males of Selenops bani Alayon-Garcia, 1992 and Selenops
      marcanoi Alayon-Garcia, 1992 are described for the first time, and the females of
      Selenops phaselus Muma, 1953 and Selenops geraldinae Corronca, 1996 are described
      for the first time. Almost all species are redescribed, barring Cuban endemics
      and a few species recently described. New illustrations are provided, including
      those of the internal female copulatory organs, many of which are illustrated for
      the first time. A key to species is also provided as are new distributional
      records.

PMID- 21852920
TI  - Revision of Diplocirrus Haase, 1915, including Bradiella Rullier, 1965, and
      Diversibranchius Buzhinskaja, 1993 (Polychaeta, Flabelligeridae).
AB  - Diplocirrus Haase, 1915, includes flabelligerids having cylindrical to club
      shaped bodies, with cirriform papillae, multiarticulate chaetae in both
      parapodial rami, 8 branchial filaments of two types (thick and rarely lamellate,
      or cirriform), gonopodial lobes in chaetigers 5 or 6, or multiple gonopores along
      some anterior chaetigers. Bradiella Rullier, 1965, has included only the type
      species: Bradiella branchiata Rullier, 1965, described from Eastern Australia.
      The original description has been overlooked and it lacked enough details on
      branchial and chaetal features. Diversibranchius Buzhinskaja, 1993, with
      Diplocirrus nicolaji Buzhinskaja, 1994, as the type species, was introduced for a
      similar species from the Japan Sea. These two monotypic genera share the same
      morphologic features with Diplocirrus, and are herein regarded as its junior
      synonyms. As herein redefined, Diplocirrus includes, besides its type species,
      Diplocirrus glaucus (Malmgren, 1867)from Scandinavia : Diplocirrus branchiatus
      (Rullier, 1965), comb. n. from Queensland, Australia, Diplocirrus capensis Day,
      1961 from South Africa, Diplocirrus erythroporus Gallardo, 1968 from Vietnam,
      Diplocirrus hirsutus (Hansen, 1882) from Arctic and subarctic regions,
      Diplocirrus incognitus Darbyshire & Mackie, 2009 from South Africa, Diplocirrus
      kudenovisp. n. from off Western Mexico, Diplocirrus longisetosus (von
      Marenzeller, 1890) restricted to the Bering Sea, Diplocirrus micans Fauchald,
      1972 from deep water off Oregon and Western Mexico, Diplocirrus nicolaji
      (Buzhinskaja, 1994), comb. n. from the Japan Sea, Diplocirrus normani (McIntosh,
      1908), comb. n. from Scandinavia, Diplocirrus octobranchus (Hartman, 1965), comb.
      n. from off New England, and Diplocirrus stopbowitzi Darbyshire & Mackie, 2009
      from the Irish Sea.

PMID- 21852921
TI  - Monomorium dryhimi sp. n., a new ant species (Hymenoptera, Formicidae) of the M.
      monomorium group from Saudi Arabia, with a key to the Arabian Monomorium
      monomorium-group.
AB  - A new ant species, Monomorium dryhimi, is described based on workers from a
      single colony collected in Al Bahah, Asir Province, Saudi Arabia. This is the
      fourth species of the Monomorium monomorium-group collected from Arabian
      Peninsula, and appears to be closely related to Monomorium holothir Bolton, 1987,
      from Kenya. It can be distinguished by the following characters: head in profile
      with a weakly convex dorsal surface and a clearly convex ventral surface; eyes of
      moderate size with maximum diameter EL 0.19-0.25 * HW and with 6 ommatidia in the
      longest row; body colour yellow to light brownish yellow. In some individuals,
      head and gaster slightly but conspicuously darker than rest of body. Second
      halves of first and second gastral tergites with two characteristic brownish
      transverse bands. An identification key to the workers of the Arabian species of
      the Monomorium monomorium-group is presented. Scanning electron micrographs are
      given to illustrate the new species.

PMID- 21852922
TI  - New myrmecomorphous longhorned beetles from Haiti and the Dominican Republic with
      a key to Anaglyptini and Tillomorphini of Hispaniola (Coleoptera, Cerambycidae,
      Cerambycinae).
AB  - First records of the tribes Anaglyptini and Tillomorphini (Coleoptera:
      Cerambycidae: Cerambycinae) are documented for Hispaniola. A new genus of a
      highly myrmecomorphic longhorned beetle (Licracanthagen. n.) is described and
      illustrated based on one species (Licracantha formicariasp. n.) and provisionally
      assigned to Tillomorphini. Three other new species of ant mimic longhorned
      beetles are described and illustrated: Calliclytus macorissp. n. (Tillomorphini),
      Tilloclytus baorucosp. n., and Tilloclytus neibasp. n. (Anaglyptini). An
      identification key and distribution map to all known Hispaniolan species of these
      two tribes are presented.

PMID- 21852923
TI  - Record of the invasive alien ladybird Harmonia axyridis (Coleoptera,
      Coccinellidae) from Kenya.
AB  - The biological control agent and alien invasive ladybird Harmonia axyridis
      (Pallas, 1773) was recorded for the first time in Kenya, and in equatorial
      Africa, in 2010.

PMID- 21852924
TI  - A new species of armored scale, Mycetaspis ailynaomi (Hemiptera, Diaspididae,
      Aspidiotinae), associated with Mammea americana L. (Malpighiales, Calophyllaceae)
      from Puerto Rico.
AB  - A new species of armored scale, Mycetaspis ailynaomi Dones and Evans is described
      and illustrated from specimens collected on mamey (Mammea americana) from Puerto
      Rico. A key to the species of Mycetaspis is provided.

PMID- 21852925
TI  - Technomyrmex montaseri sp. n., a new ant species of the T. gibbosus-group from
      Oman (Hymenoptera, Formicidae) with a key to the Technomyrmex species of the
      Arabian Peninsula.
AB  - Technomyrmex montaserisp. n. is described and illustrated from Oman based on the
      worker caste collected in Bani Sur. It belongs to the Technomyrmex gibbosus
      group, with closest resemblance to Technomyrmex vexatus (Santschi, 1919) and
      Technomyrmex gibbosus W. M. Wheeler, 1906. A key to the Arabian Technomyrmex is
      given.

PMID- 21852926
TI  - Systematics of Australian Thrasorinae (Hymenoptera, Cynipoidea, Figitidae) with
      descriptions of Mikeiinae, new subfamily, two new genera, and three new species.
AB  - The Australian Thrasorinae are revised and Mikeius is transferred to Mikeiinae
      Paretas-Martinez & Pujade-Villar, subfam. n., and Mikeius clavatus Pujade-Villar
      & Restrepo-Ortiz, sp. n., is described. Two new genera of Thrasorinae are
      erected: Cicatrix Paretas-Martinez, gen. n., including Cicatrix
      pilosiscutum(Girault), comb. n. from Amblynotus, Cicatrix schauffi (Buffington),
      comb. n. from Mikeius, and Cicatrix neumannoides Paretas-Martinez & Restrepo
      Ortiz, sp. n.; and Palmiriella Pujade-Villar & Paretas-Martinez, gen. n.,
      including Palmiriella neumanni (Buffington), comb. n. from Mikeius, Thrasorus
      rieki Paretas-Martinez & Pujade-Villar, sp. n., is also described. A phylogenetic
      analysis of 176 morphological and biological characters, including all these new
      taxa and all genera previously included in Thrasorinae, was conducted. All
      subfamilies were recovered as monophyletic, with the following relationships:
      Parnipinae (Euceroptrinae (Mikeiinae (Plectocynipinae (Thrasorinae)))). A
      worldwide key to the subfamilies of Figitidae is provided that includes the new
      subfamily, as well as a key to genera Thrasorinae.

PMID- 21852927
TI  - Notes on the genus Ismarus Haliday (Hymenoptera, Diapriidae) from China.
AB  - The Chinese species of the genus Ismarus Haliday, 1835, are revised for the first
      time. Three new species from the Oriental region of China and belonging to
      Ismarus halidayi-group are described and illustrated: Ismarus longussp. n.,
      Ismarus nigritrochantersp. n. and Ismarus parvicellussp. n. Two species are newly
      reported for the Chinese fauna: Ismarus dorsiger (Haliday, 1831) and Ismarus
      halidayi Foerster, 1850. A key to the Chinese species of the genus is provided.
      The type specimens are deposited in the Hymenopteran Collection of South China
      Agricultural University, Guangzhou (SCAU).

PMID- 21852928
TI  - A new species of the genus Palpostilpnus Aubert (Hymenoptera, Ichneumonidae,
      Cryptinae) from the Oriental part of China.
AB  - Palpostilpnus brevis Sheng & Broad, sp.n., belonging to the tribe Phygadeuontini
      of the subfamily Cryptinae (Hymenoptera, Ichneumonidae), collected from Jiangxi
      Province, China, is described. A key to the described species of the genus
      Palpostilpnus Aubert, 1961, is provided.

PMID- 21852929
TI  - A new Stenoloba Staudinger species from China (Lepidoptera, Noctuidae,
      Bryophilinae).
AB  - A new species of Stenoloba, Stenoloba viridicollarsp. n. (Lepidoptera, Noctuidae)
      is described from Sichuan, China. Illustrations of adults and the genitalia of
      both sexes are provided. A diagnostic comparison is made with Stenoloba
      rufosagitta Kononenko & Ronkay, 2001 and S. rufosagittoides Han & Kononenko,
      2009.

PMID- 21852930
TI  - A new species of Andean toad (Bufonidae, Osornophryne) discovered using molecular
      and morphological data, with a taxonomic key for the genus.
AB  - Combining a molecular phylogeny and morphological data, we discovered a new
      species of Osornophryne from the Amazonian slope of the Ecuadorian Andes.
      Morphologically, the new taxon is distinguished from all others species in
      Osornophryne by having the Toes IV and V longer than Toes I-III, a short and
      rounded snout with a small rostral papilla, and conical pustules on flanks. The
      new species previously was confused with Osornophryne guacamayo. A taxonomic key
      is provided for all known species of Osornophryne.

PMID- 21852931
TI  - Two new species of Andean gymnophthalmid lizards of the genus Euspondylus
      (Reptilia, Squamata) from central and southern Peru.
AB  - Two new species of lizards assigned to the genus Euspondylus from the montane
      forests of the Peruvian Andes in the Pasco Department (central Peru) and Ayacucho
      Department (southern Peru) both at elevations of 2550 and 3450 m, respectively,
      are described. The new species are distinguishable from all other Peruvian and
      Ecuadorian species of Euspondylus by a unique combination of morphometric,
      scalation and color pattern characteristics. Natural history data for the new
      species and for Euspondylus spinalis are also provided.

PMID- 21852932
TI  - The herpetofauna of Timor-Leste: a first report.
AB  - Fieldwork conducted throughout Timor-Leste in September 2004 and July 2009
      resulted in a collection or recording of 263 herpetological specimens (100
      amphibians, 163 reptiles), comprising at least seven species of frogs and toads,
      20 species of lizards, seven species of snakes, two species of turtles, and one
      species of crocodile. Among the amphibians, the most frequently encountered
      species were toads (Duttaphrynus melanostictus), rice paddy frogs (genus
      Fejervarya), and rhacophorid treefrogs (Polypedates cf. leucomystax). All three
      variants of rice paddy frogs encountered represent undescribed species similar to
      Fejervarya verruculosa from neighboring Wetar Island. Records of Fejervarya
      cancrivora and Fejervarya limnocharis for Timor Island are apparently errors
      based on misidentification. We obtained voucher specimens for a total of 147
      lizards and voucher photographs only for four specimens of Varanus timorensis.
      Aside from geckos frequently associated with human habitations (e.g., Gehyra
      mutilata, Gekko gecko, Hemidactylus frenatus, Hemidactylus platyurus), we
      discovered an as yet undescribed species of bent-toed gecko, genus Cyrtodactylus,
      in the Same valley. Our specimens of Hemidactylus platyurus are the first record
      of this species from Timor-Leste. Commonly encountered skinks included four
      fingered skinks (genus Carlia), wedge skinks (genus Sphenomorphus), and night
      skinks (genus Eremiascincus). Notable among the 15 snakes collected was the
      frequency of pitvipers (Cryptelytrops insularis), which amounted to over 25% of
      all snakes. Our specimen of the wolfsnake Lycodon subcinctus is the first record
      of this species for Timor-Leste. Based on these findings, it appears that the
      biodiversity of amphibians and reptiles in this remote corner of Wallacea is much
      greater than previously thought, particularly with respect to scincid lizards.
      The detail we provide in the species accounts is designed to allow the use of
      this report as a preliminary field guide to the amphibians and reptiles of Timor
      Leste. However, survey work is ongoing.

PMID- 21852933
TI  - A revision of the Chinese Stephanidae (Hymenoptera, Stephanoidea).
AB  - Stephanidae Leach, 1815 (Hymenoptera: Stephanoidea) from China are revised. Five
      genera are reported from China: Foenatopus Smith, 1861; Megischus Brulle, 1846;
      Parastephanellus Enderlein, 1906; Schlettererius Ashmead, 1900; and Stephanus
      Jurine (in Panzer), 1801, and the genera are keyed. All the Chinese species are
      described and illustrated and new synonyms are established. Keys to species of
      the five genera occurring in China and adjacent regions are provided.SIX SPECIES
      ARE NEW TO SCIENCE: Foenatopus brevimaculatussp. n., Foenatopus maculiferussp.
      n., Foenatopus yangisp. n., Parastephanellus angulatussp. n., Parastephanellus
      brevicoxalissp. n. and Parastephanellus zhejiangensissp. n. One species,
      Parastephanellus matsumotoi van Achterberg, 2006, is newly recorded from
      China.The following 9 new synonyms are proposed: Foenatopus aratifrons Enderlein,
      1913 and Foenatopus yunnanensis Chao, 1964, new synonymys for Foenatopus
      annulitarsus Enderlein, 1913; Foenatopus cerviculatus (Chao, 1964) and Foenatopus
      chaoi Belokobylskij, 1995 for Foenatopus chinensis (Elliott, 1919); Foenatopus
      formosanus Enderlein, 1913 for Foenatopus cinctus (Matsumura, 1912); Foenatopus
      simillimus (Elliott, 1920) and Foenatopus trilineatus (Elliott, 1920) for
      Foenatopus flavidentatus (Enderlein, 1913); Foenatopus trilobatus (Elliott, 1920)
      for Foenatopus ruficollis (Enderlein, 1913); Parastephanellus austrochinensis
      Belokobylskij, 1995 for Parastephanellus brevistigma Enderlein, 1913. A lectotype
      is designated for Diastephanus trilineatus Elliott, 1920.

PMID- 21852934
TI  - Asiphonipponaphis, a new genus of Hormaphidinae (Hemiptera, Aphididae) causing
      galls on Distylium chinense from China, with description of a new species.
AB  - The aphid genus Asiphonipponaphisgen. n. from China is new to science.
      Asiphonipponaphis vasigallasp. n. causing galls on Distylium chinense from Hunan,
      China is described and illustrated. Holotype and paratypes are deposited in the
      National Zoological Museum of China, Institute of Zoology, Chinese Academy of
      Sciences, Beijing, China (NZMCAS) and Kogakkan University, Japan.

PMID- 21852935
TI  - Taxonomic position of Hormaphis similibetulae Qiao & Zhang, 2004 (Hemiptera,
      Aphididae): molecular and biological evidences.
AB  - The taxonomic position of Hormaphis similibetulae Qiao & Zhang, 2004 has been
      reexamined. The phylogenetic position of Hormaphis similibetulae was inferred by
      maximum parsimony, maximum likelihood and Bayesian analyses on the basis of
      partial nuclear elongation factor-1alpha and mitochondrial tRNA
      leucine/cytochrome oxidase II sequences. The results showed that this species
      fell into the clade of Hamamelistes species, occupying a basal position, and was
      clearly distinct from other Hormaphis species. A closer relationship between
      Hormaphis similibetulae and Hamamelistes species was also revealed by life cycle
      analysis. Therefore, we conclude that Hormaphis similibetulae should be
      transferred to the genus Hamamelistes as Hamamelistes similibetulae (Qiao &
      Zhang), comb. n.

PMID- 21852936
TI  - The identity of the Neotropical stingless bee Frieseomelitta meadewaldoi
      (Cockerell, 1915) (Hymenoptera, Apidae).
AB  - A new study of a surviving syntype of Trigona meadewaldoi Cockerell, 1915, was
      undertaken and several widely employed names for Neotropical stingless bees
      recognized as junior synonyms. A lectotype is designated for Trigona meadewaldoi
      and the following new synonymies established: Tetragona francoi Moure, 1946, and
      Trigona (Frieseomelitta) freiremaiai Moure, 1963. These nomenclatural matters are
      here settled and the species thoroughly characterized in advance of a forthcoming
      phylogenetic consideration of the genus Frieseomelitta von Ihering, 1912.

PMID- 21852937
TI  - A new species of Microsphecodes from Jamaica (Hymenoptera, Halictidae).
AB  - A new species of the cleptoparasitic bee genus Microsphecodes Eickwort and Stage
      (Halictinae: Halictini) is described and figured from a male and female collected
      in Jamaica. Microsphecodes xaymacensis Engel, sp. n., is distinguished from its
      congeners on the basis of integumental coloration and sculpturing, and form of
      the male pygidial plate and genitalia.

PMID- 21852938
TI  - A new species of the bee genus Ctenoplectrella in middle Eocene Baltic amber
      (Hymenoptera, Megachilidae).
AB  - A new species of the extinct bee genus Ctenoplectrella Cockerell (Megachilinae:
      Ctenoplectrellini) is described and figured from two females preserved in middle
      Eocene (Lutetian) Baltic amber. Ctenoplectrella phaetonsp. n. is distinguished
      from its congeners on the basis of its body proportions, integumental
      sculpturing, wing venation, and pubescence, and is one of the more distinctive
      members of the genus. A revised key to the species of Ctenoplectrella is
      provided.

PMID- 21852939
TI  - Parachorius semsanganus sp. n. (Coleoptera, Scarabaeidae, Scarabaeinae) from Laos
      and its significance in the phylogeny of Oriental Deltochilini.
AB  - The new species Parachorius semsanganussp. n. is described from Laos. This
      enigmatic Oriental deltochiline represents a "morphological link" between
      Parachorius and Cassolus by sharing characters of the two genera. The fact that
      Parachorius semsanganus cannot be unequivocally placed in either of these two
      genera stresses some more general problems of the current classification of
      Parachorius and Cassolus. Such problems can be solved only in the course of
      phylogenetic analysis, the need of which is briefly outlined.

PMID- 21852940
TI  - A new species of Amphoropsyche (Trichoptera, Leptoceridae) from Ecuador, with a
      key to the species in the genus.
AB  - A new species of Amphoropsyche Holzenthal is described from Ecuador. It is
      similar to a group of species with dorsomesal processes on the preanal appendages
      (i.e., Amphoropsyche woodruffi Flint & Sykora, Amphoropsyche refugia Holzenthal,
      and Amphoropsyche aragua Holzenthal), but can be distinguished from these and
      other members of the genus by the short, digitate dorsomesal processes on the
      preanal appendages and the broad lateral processes of tergum X of the male
      genitalia. A key to males of the 14 species now known in the genus is presented
      based on characters of the genitalia.

PMID- 21852941
TI  - On Chinese species of Dianous group I (Coleoptera, Staphylinidae, Steninae).
AB  - Chinese species of Dianous group I are studied and three new species are
      described: Dianous fengtingaesp. n. from Hainan Province, Dianous zhujianqingisp.
      n. from Jiangxi and Guizhou Province, and Dianous huanghaoisp. n. from Yunnan
      Province. Dianous shan Rougemont and Dianous viridicupreus Rougemont are
      discovered from China for the first time. Their diagnostic characters are
      illustrated and a key to Chinese species of Dianous group I is provided.

PMID- 21852942
TI  - A Unique BSL-3 Cryo-Electron Microscopy Laboratory at UTMB.
AB  - This article describes a unique cryo-electron microscopy (CryoEM) facility to
      study the three-dimensional organization of viruses at biological safety level 3
      (BSL-3). This facility, the W. M. Keck Center for Virus Imaging, has successfully
      operated for more than a year without incident and was cleared for select agent
      studies by the Centers for Disease Control and Prevention (CDC). Standard
      operating procedures for the laboratory were developed and implemented to ensure
      its safe and efficient operation. This facility at the University of Texas
      Medical Branch (Galveston, TX) is the only such BSL-3 CryoEM facility approved
      for select agent research.

PMID- 21852943
TI  - Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
AB  - Cortico-basal ganglia-thalamocortical circuits are severely disrupted by the
      dopamine depletion of Parkinson's disease (PD), leading to pathologically
      exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes
      are correlated with movement impairments but their neural basis remains unclear.
      Here, we used dynamic causal modelling (DCM) and the 6-hydroxydopamine-lesioned
      rat model of PD to examine the effective connectivity underlying these spectral
      abnormalities. We acquired auto-spectral and cross-spectral measures of beta
      oscillations (10-35 Hz) from local field potential recordings made simultaneously
      in the frontal cortex, striatum, external globus pallidus (GPe) and subthalamic
      nucleus (STN), and used these data to optimise neurobiologically plausible
      models. Chronic dopamine depletion reorganised the cortico-basal ganglia
      thalamocortical circuit, with increased effective connectivity in the pathway
      from cortex to STN and decreased connectivity from STN to GPe. Moreover, a
      contribution analysis of the Parkinsonian circuit distinguished between
      pathogenic and compensatory processes and revealed how effective connectivity
      along the indirect pathway acquired a strategic importance that underpins beta
      oscillations. In modelling excessive beta synchrony in PD, these findings provide
      a novel perspective on how altered connectivity in basal ganglia-thalamocortical
      circuits reflects a balance between pathogenesis and compensation, and predicts
      potential new therapeutic targets to overcome dysfunctional oscillations.

PMID- 21852944
TI  - Structure and dynamics of the membrane-bound cytochrome P450 2C9.
AB  - The microsomal, membrane-bound, human cytochrome P450 (CYP) 2C9 is a liver
      specific monooxygenase essential for drug metabolism. CYPs require electron
      transfer from the membrane-bound CYP reductase (CPR) for catalysis. The
      structural details and functional relevance of the CYP-membrane interaction are
      not understood. From multiple coarse grained molecular simulations started with
      arbitrary configurations of protein-membrane complexes, we found two predominant
      orientations of CYP2C9 in the membrane, both consistent with experiments and
      conserved in atomic-resolution simulations. The dynamics of membrane-bound and
      soluble CYP2C9 revealed correlations between opening and closing of different
      tunnels from the enzyme's buried active site. The membrane facilitated the
      opening of a tunnel leading into it by stabilizing the open state of an internal
      aromatic gate. Other tunnels opened selectively in the simulations of product
      bound CYP2C9. We propose that the membrane promotes binding of liposoluble
      substrates by stabilizing protein conformations with an open access tunnel and
      provide evidence for selective substrate access and product release routes in
      mammalian CYPs. The models derived here are suitable for extension to incorporate
      other CYPs for oligomerization studies or the CYP reductase for studies of the
      electron transfer mechanism, whereas the modeling procedure is generally
      applicable to study proteins anchored in the bilayer by a single transmembrane
      helix.

PMID- 21852945
TI  - The cytokine network of acute HIV infection: a promising target for vaccines and
      therapy to reduce viral set-point?
AB  - Cytokines play a central role in the pathogenesis of many diseases, including HIV
      infection. However, the role of the cytokine network in early HIV infection is
      only now starting to be elucidated. A number of studies conducted in recent years
      have indicated that cytokines of the acute/early stages of HIV and SIV infection
      can impact viral set-point months later, and this is of critical importance since
      viral set-point during chronic HIV infection affects virus transmission and
      disease progression. This raises the question whether modulating the cytokine
      environment during acute/early HIV infection can be a target for novel approaches
      to develop a vaccine and therapeutics. In this review we focus on the kinetics
      and function of cytokines during acute HIV and SIV infection and how these may
      impact viral set-point. We also discuss unresolved questions that are essential
      for our understanding of the role of acute infection cytokines in HIV infection
      and that, if answered, may suggest novel therapeutic and vaccine strategies to
      control the worldwide HIV pandemic.

PMID- 21852946
TI  - B cell repertoire analysis identifies new antigenic domains on glycoprotein B of
      human cytomegalovirus which are target of neutralizing antibodies.
AB  - Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed
      pathogen that causes severe disease in immunosuppressed patients and infected
      newborns. Efforts are underway to prepare effective subunit vaccines and
      therapies including antiviral antibodies. However, current vaccine efforts are
      hampered by the lack of information on protective immune responses against HCMV.
      Characterizing the B-cell response in healthy infected individuals could aid in
      the design of optimal vaccines and therapeutic antibodies. To address this
      problem, we determined, for the first time, the B-cell repertoire against
      glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in
      an unbiased fashion. HCMV gB represents a dominant viral antigenic determinant
      for induction of neutralizing antibodies during infection and is also a component
      in several experimental HCMV vaccines currently being tested in humans. Our
      findings have revealed that the vast majority (>90%) of gB-specific antibodies
      secreted from B-cell clones do not have virus neutralizing activity. Most
      neutralizing antibodies were found to bind to epitopes not located within the
      previously characterized antigenic domains (AD) of gB. To map the target
      structures of these neutralizing antibodies, we generated a 3D model of HCMV gB
      and used it to identify surface exposed protein domains. Two protein domains were
      found to be targeted by the majority of neutralizing antibodies. Domain I,
      located between amino acids (aa) 133-343 of gB and domain II, a discontinuous
      domain, built from residues 121-132 and 344-438. Analysis of a larger panel of
      human sera from HCMV seropositive individuals revealed positivity rates of >50%
      against domain I and >90% against domain II, respectively. In accordance with
      previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I),
      respectively. Collectively, these data will contribute to optimal vaccine design
      and development of antibodies effective in passive immunization.

PMID- 21852947
TI  - Association of human TLR1 and TLR6 deficiency with altered immune responses to
      BCG vaccination in South African infants.
AB  - The development of effective immunoprophylaxis against tuberculosis (TB) remains
      a global priority, but is hampered by a partially protective Bacillus Calmette
      Guerin (BCG) vaccine and an incomplete understanding of the mechanisms of
      immunity to Mycobacterium tuberculosis. Although host genetic factors may be a
      primary reason for BCG's variable and inadequate efficacy, this possibility has
      not been intensively examined. We hypothesized that Toll-like receptor (TLR)
      variation is associated with altered in vivo immune responses to BCG. We examined
      whether functionally defined TLR pathway polymorphisms were associated with T
      cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after
      newborn BCG vaccination of South African infants. In the primary analysis,
      polymorphism TLR6_C745T (P249S) was associated with increased BCG-induced IFN
      gamma in both discovery (n = 240) and validation (n = 240) cohorts. In secondary
      analyses of the combined cohort, TLR1_T1805G (I602S) and TLR6_G1083C (synonymous)
      were associated with increased IFN-gamma, TLR6_G1083C and TLR6_C745T were
      associated with increased IL-2, and TLR1_A1188T was associated with increased IFN
      gamma and IL-2. For each of these polymorphisms, the hypo-responsive allele, as
      defined by innate immunity signaling assays, was associated with increased
      production of TH1-type T cell cytokines (IFN-gamma or IL-2). After stimulation
      with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals
      (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted
      lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6
      genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These
      data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell
      polarization through genetic regulation of monocyte IL-10 secretion in the
      absence of IL-12. These studies provide evidence that functionally defined innate
      immune gene variants are associated with the development of adaptive immune
      responses after in vivo vaccination against a bacterial pathogen in humans. These
      findings could potentially guide novel adjuvant vaccine strategies as well as
      have implications for IFN-gamma-based diagnostic testing for TB.

PMID- 21852948
TI  - Characterisation of regulatory T cells in nasal associated lymphoid tissue in
      children: relationships with pneumococcal colonization.
AB  - Regulatory T cells (Treg) diminish immune responses to microbial infection, which
      may contribute to preventing inflammation-related local tissue damage and
      autoimmunity but may also contribute to chronicity of infection. Nasopharyngeal
      carriage of pneumococcus is common in young children and can persist for long
      periods but it is unknown whether the presence of Treg in the nasopharynx
      contributes to this persistence. We have investigated the numbers and activities
      of Foxp3+Treg in adenoidal tissues and their association with pneumococcal
      carriage in children. Expression of Treg cell-related markers including Foxp3,
      CD25, CD39, CD127 and CLTA4 were analysed by flow-cytometry in adenoidal
      mononuclear cells (MNC) and PBMC from children. Unfractionated MNC or Treg
      depleted MNC were stimulated with a pneumococcal whole cell antigen (WCA) and T
      cell proliferation measured. Cytokine production by MNC was measured using a
      cytometric bead array. Higher numbers of CD25(high)Foxp3(high) Treg expressing
      higher CD39 and CTLA4 were found in adenoidal MNC than in PBMC. Children with
      pneumococcus positive nasopharyngeal cultures had higher proportions of Treg and
      expressed higher levels of CD39 and CTLA-4 than those who were culture negative (
      ). WCA induced adenoidal Treg proliferation which produce IL10 but not IL17, and
      CD4 T cell proliferation in Treg-depleted MNC was greater in pneumococcal culture
      positive than negative children. Significant numbers of Treg with an
      effector/memory phenotype which possess a potent inhibitory effect, exist in
      adenoidal tissue. The association of pneumococcal carriage with an increased
      frequency of adenoidal Treg suggests that Treg in nasal-associated lymphoid
      tissue (NALT) may contribute to the persistence of pneumococcus in children.
      Further studies to determine what component and mechanisms are involved in the
      promotion of Treg in NALT may lead to novel therapeutic or vaccination strategy
      against upper respiratory infection.

PMID- 21852949
TI  - Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1,
      for controlling pathogenicity of Cryptococcus neoformans.
AB  - In eukaryotic cells, the unfolded protein response (UPR) pathway plays a crucial
      role in cellular homeostasis of the endoplasmic reticulum (ER) during exposure to
      diverse environmental conditions that cause ER stress. Here we report that the
      human fungal pathogen Cryptococcus neoformans has evolved a unique UPR pathway
      composed of an evolutionarily conserved Ire1 protein kinase and a novel bZIP
      transcription factor encoded by HXL1 (HAC1 and XBP1-Like gene 1). C. neoformans
      HXL1 encodes a protein lacking sequence homology to any known fungal or mammalian
      Hac1/Xbp1 protein yet undergoes the UPR-induced unconventional splicing in an
      Ire1-dependent manner upon exposure to various stresses. The structural
      organization of HXL1 and its unconventional splicing is widely conserved in C.
      neoformans strains of divergent serotypes. Notably, both C. neoformans ire1 and
      hxl1 mutants exhibited extreme growth defects at 37 degrees C and
      hypersensitivity to ER stress and cell wall destabilization. All of the growth
      defects of the ire1 mutant were suppressed by the spliced active form of Hxl1,
      supporting that HXL1 mRNA is a downstream target of Ire1. Interestingly, however,
      the ire1 and hxl1 mutants showed differences in thermosensitivity, expression
      patterns for a subset of genes, and capsule synthesis, indicating that Ire1 has
      both Hxl1-dependent and -independent functions in C. neoformans. Finally, Ire1
      and Hxl1 were shown to be critical for virulence of C. neoformans, suggesting UPR
      signaling as a novel antifungal therapeutic target.

PMID- 21852950
TI  - Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1
      influenza A virus in mammalian and avian species.
AB  - Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype
      occasionally transmit from birds to humans and can cause severe systemic
      infections in both hosts. PB1-F2 is an alternative translation product of the
      viral PB1 segment that was initially characterized as a pro-apoptotic
      mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present
      in all human influenza pandemic virus isolates of the 20(th) century, but appears
      to be lost evolutionarily over time as the new virus establishes itself and
      circulates in the human host. In contrast, the open reading frame (ORF) for PB1
      F2 is exceptionally well-conserved in avian influenza virus isolates. Here we
      perform a comparative study to show for the first time that PB1-F2 is a
      pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both
      mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that
      was previously described to be associated with high lethality of the 1918
      influenza A virus showed increased replication and virulence of a recombinant
      VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible
      effects. Interestingly, the N66S substituted virus efficiently invades the CNS
      and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly
      resulted in delayed onset of clinical symptoms and systemic spreading of virus,
      while variations at position 66 played only a minor role in pathogenesis. These
      data implicate PB1-F2 as an important pathogenicity factor in ducks independent
      of sequence variations at position 66. Our data could explain why PB1-F2 is
      conserved in avian influenza virus isolates and only impacts pathogenicity in
      mammals when containing certain amino acid motifs such as the rare N66S
      polymorphism.

PMID- 21852951
TI  - Variance of gene expression identifies altered network constraints in
      neurological disease.
AB  - Gene expression analysis has become a ubiquitous tool for studying a wide range
      of human diseases. In a typical analysis we compare distinct phenotypic groups
      and attempt to identify genes that are, on average, significantly different
      between them. Here we describe an innovative approach to the analysis of gene
      expression data, one that identifies differences in expression variance between
      groups as an informative metric of the group phenotype. We find that genes with
      different expression variance profiles are not randomly distributed across cell
      signaling networks. Genes with low-expression variance, or higher constraint, are
      significantly more connected to other network members and tend to function as
      core members of signal transduction pathways. Genes with higher expression
      variance have fewer network connections and also tend to sit on the periphery of
      the cell. Using neural stem cells derived from patients suffering from
      Schizophrenia (SZ), Parkinson's disease (PD), and a healthy control group, we
      find marked differences in expression variance in cell signaling pathways that
      shed new light on potential mechanisms associated with these diverse neurological
      disorders. In particular, we find that expression variance of core networks in
      the SZ patient group was considerably constrained, while in contrast the PD
      patient group demonstrated much greater variance than expected. One hypothesis is
      that diminished variance in SZ patients corresponds to an increased degree of
      constraint in these pathways and a corresponding reduction in robustness of the
      stem cell networks. These results underscore the role that variation plays in
      biological systems and suggest that analysis of expression variance is far more
      important in disease than previously recognized. Furthermore, modeling patterns
      of variability in gene expression could fundamentally alter the way in which we
      think about how cellular networks are affected by disease processes.

PMID- 21852952
TI  - Gamma-tubulin is required for bipolar spindle assembly and for proper kinetochore
      microtubule attachments during prometaphase I in Drosophila oocytes.
AB  - In many animal species the meiosis I spindle in oocytes is anastral and lacks
      centrosomes. Previous studies of Drosophila oocytes failed to detect the native
      form of the germline-specific gamma-tubulin (gammaTub37C) in meiosis I spindles,
      and genetic studies have yielded conflicting data regarding the role of
      gammaTub37C in the formation of bipolar spindles at meiosis I. Our examination of
      living and fixed oocytes carrying either a null allele or strong missense
      mutation in the gammatub37C gene demonstrates a role for gammaTub37C in the
      positioning of the oocyte nucleus during late prophase, as well as in the
      formation and maintenance of bipolar spindles in Drosophila oocytes. Prometaphase
      I spindles in gammatub37C mutant oocytes showed wide, non-tapered spindle poles
      and disrupted positioning. Additionally, chromosomes failed to align properly on
      the spindle and showed morphological defects. The kinetochores failed to properly
      co-orient and often lacked proper attachments to the microtubule bundles,
      suggesting that gammaTub37C is required to stabilize kinetochore microtubule
      attachments in anastral spindles. Although spindle bipolarity was sometimes
      achieved by metaphase I in both gammatub37C mutants, the resulting chromosome
      masses displayed highly disrupted chromosome alignment. Therefore, our data
      conclusively demonstrate a role for gammaTub37C in both the formation of the
      anastral meiosis I spindle and in the proper attachment of kinetochore
      microtubules. Finally, multispectral imaging demonstrates the presences of native
      gammaTub37C along the length of wild-type meiosis I spindles.

PMID- 21852953
TI  - The Caenorhabditis elegans T-box factor MLS-1 requires Groucho co-repressor
      interaction for uterine muscle specification.
AB  - T-box proteins are conserved transcription factors that play crucial roles in
      development of all metazoans; and, in humans, mutations affecting T-box genes are
      associated with a variety of congenital diseases and cancers. Despite the
      importance of this transcription factor family, very little is known regarding
      how T-box factors regulate gene expression. The Caenorhabditis elegans genome
      contains 21 T-box genes, and their characterized functions include cell fate
      specification in a variety of tissues. The C. elegans Tbx1 sub-family member MLS
      1 functions during larval development to specify the fate of non-striated uterine
      muscles; and, in mls-1 mutants, uterine muscles are transformed to a vulval
      muscle fate. Here we demonstrate that MLS-1 function depends on binding to the
      Groucho-family co-repressor UNC-37. MLS-1 interacts with UNC-37 via a conserved
      eh1 motif, and the MLS-1 eh1 motif is necessary for MLS-1 to specify uterine
      muscle fate. Moreover, unc-37 loss-of-function produces uterine muscle to vulval
      muscle fate transformation similar to those observed in mls-1 mutants. Based on
      these results, we conclude that MLS-1 specifies uterine muscle fate by repressing
      target gene expression, and this function depends on interaction with UNC-37.
      Moreover, we suggest that MLS-1 shares a common mechanism for transcriptional
      repression with related T-box factors in other animal phyla.

PMID- 21852954
TI  - Polo, greatwall, and protein phosphatase PP2A Jostle for pole position.

PMID- 21852955
TI  - Discovery of sexual dimorphisms in metabolic and genetic biomarkers.
AB  - Metabolomic profiling and the integration of whole-genome genetic association
      data has proven to be a powerful tool to comprehensively explore gene regulatory
      networks and to investigate the effects of genetic variation at the molecular
      level. Serum metabolite concentrations allow a direct readout of biological
      processes, and association of specific metabolomic signatures with complex
      diseases such as Alzheimer's disease and cardiovascular and metabolic disorders
      has been shown. There are well-known correlations between sex and the incidence,
      prevalence, age of onset, symptoms, and severity of a disease, as well as the
      reaction to drugs. However, most of the studies published so far did not consider
      the role of sexual dimorphism and did not analyse their data stratified by
      gender. This study investigated sex-specific differences of serum metabolite
      concentrations and their underlying genetic determination. For discovery and
      replication we used more than 3,300 independent individuals from KORA F3 and F4
      with metabolite measurements of 131 metabolites, including amino acids,
      phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear
      regression approach revealed significant concentration differences between males
      and females for 102 out of 131 metabolites (p-values<3.8*10(-4); Bonferroni
      corrected threshold). Sex-specific genome-wide association studies (GWAS) showed
      genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus
      (carbamoyl-phosphate synthase 1, significance level: p<3.8*10(-10); Bonferroni
      corrected threshold) for glycine. We showed that the metabolite profiles of males
      and females are significantly different and, furthermore, that specific genetic
      variants in metabolism-related genes depict sexual dimorphism. Our study provides
      new important insights into sex-specific differences of cell regulatory processes
      and underscores that studies should consider sex-specific effects in design and
      interpretation.

PMID- 21852956
TI  - Suppression of scant identifies Endos as a substrate of greatwall kinase and a
      negative regulator of protein phosphatase 2A in mitosis.
AB  - Protein phosphatase 2A (PP2A) plays a major role in dephosphorylating the targets
      of the major mitotic kinase Cdk1 at mitotic exit, yet how it is regulated in
      mitotic progression is poorly understood. Here we show that mutations in either
      the catalytic or regulatory twins/B55 subunit of PP2A act as enhancers of
      gwl(Scant), a gain-of-function allele of the Greatwall kinase gene that leads to
      embryonic lethality in Drosophila when the maternal dosage of the mitotic kinase
      Polo is reduced. We also show that heterozygous mutant endos alleles suppress
      heterozygous gwl(Scant); many more embryos survive. Furthermore, heterozygous
      PP2A mutations make females heterozygous for the strong mutation polo(11)
      partially sterile, even in the absence of gwl(Scant). Heterozygosity for an endos
      mutation suppresses this PP2A/polo(11) sterility. Homozygous mutation or
      knockdown of endos leads to phenotypes suggestive of defects in maintaining the
      mitotic state. In accord with the genetic interactions shown by the gwl(Scant)
      dominant mutant, the mitotic defects of Endos knockdown in cultured cells can be
      suppressed by knockdown of either the catalytic or the Twins/B55 regulatory
      subunits of PP2A but not by the other three regulatory B subunits of Drosophila
      PP2A. Greatwall phosphorylates Endos at a single site, Ser68, and this is
      essential for Endos function. Together these interactions suggest that Greatwall
      and Endos act to promote the inactivation of PP2A-Twins/B55 in Drosophila. We
      discuss the involvement of Polo kinase in such a regulatory loop.

PMID- 21852957
TI  - dlx and sp6-9 Control optic cup regeneration in a prototypic eye.
AB  - Optic cups are a structural feature of diverse eyes, from simple pit eyes to
      camera eyes of vertebrates and cephalopods. We used the planarian prototypic eye
      as a model to study the genetic control of optic cup formation and regeneration.
      We identified two genes encoding transcription factors, sp6-9 and dlx, that were
      expressed in the eye specifically in the optic cup and not the photoreceptor
      neurons. RNAi of these genes prevented formation of visible optic cups during
      regeneration. Planarian regeneration requires an adult proliferative cell
      population with stem cell-like properties called the neoblasts. We found that
      optic cup formation occurred only after migration of progressively
      differentiating progenitor cells from the neoblast population. The eye
      regeneration defect caused by dlx and sp6-9 RNAi can be explained by a failure to
      generate these early optic cup progenitors. Dlx and Sp6-9 genes function as a
      module during the development of diverse animal appendages, including vertebrate
      and insect limbs. Our work reveals a novel function for this gene pair in the
      development of a fundamental eye component, and it utilizes these genes to
      demonstrate a mechanism for total organ regeneration in which extensive cell
      movement separates new cell specification from organ morphogenesis.

PMID- 21852958
TI  - PP2A-twins is antagonized by greatwall and collaborates with polo for cell cycle
      progression and centrosome attachment to nuclei in drosophila embryos.
AB  - Cell division and development are regulated by networks of kinases and
      phosphatases. In early Drosophila embryogenesis, 13 rapid nuclear divisions take
      place in a syncytium, requiring fine coordination between cell cycle regulators.
      The Polo kinase is a conserved, crucial regulator of M-phase. We have recently
      reported an antagonism between Polo and Greatwall (Gwl), another mitotic kinase,
      in Drosophila embryos. However, the nature of the pathways linking them remained
      elusive. We have conducted a comprehensive screen for additional genes
      functioning with polo and gwl. We uncovered a strong interdependence between Polo
      and Protein Phosphatase 2A (PP2A) with its B-type subunit Twins (Tws). Reducing
      the maternal contribution of Polo and PP2A-Tws together is embryonic lethal. We
      found that Polo and PP2A-Tws collaborate to ensure centrosome attachment to
      nuclei. While a reduction in Polo activity leads to centrosome detachments
      observable mostly around prophase, a reduction in PP2A-Tws activity leads to
      centrosome detachments at mitotic exit, and a reduction in both Polo and PP2A-Tws
      enhances the frequency of detachments at all stages. Moreover, we show that Gwl
      antagonizes PP2A-Tws function in both meiosis and mitosis. Our study highlights
      how proper coordination of mitotic entry and exit is required during embryonic
      cell cycles and defines important roles for Polo and the Gwl-PP2A-Tws pathway in
      this process.

PMID- 21852959
TI  - Analysis of DNA methylation in a three-generation family reveals widespread
      genetic influence on epigenetic regulation.
AB  - The methylation of cytosines in CpG dinucleotides is essential for cellular
      differentiation and the progression of many cancers, and it plays an important
      role in gametic imprinting. To assess variation and inheritance of genome-wide
      patterns of DNA methylation simultaneously in humans, we applied reduced
      representation bisulfite sequencing (RRBS) to somatic DNA from six members of a
      three-generation family. We observed that 8.1% of heterozygous SNPs are
      associated with differential methylation in cis, which provides a robust
      signature for Mendelian transmission and relatedness. The vast majority of
      differential methylation between homologous chromosomes (>92%) occurs on a
      particular haplotype as opposed to being associated with the gender of the parent
      of origin, indicating that genotype affects DNA methylation of far more loci than
      does gametic imprinting. We found that 75% of genotype-dependent differential
      methylation events in the family are also seen in unrelated individuals and that
      overall genotype can explain 80% of the variation in DNA methylation. These
      events are under-represented in CpG islands, enriched in intergenic regions, and
      located in regions of low evolutionary conservation. Even though they are
      generally not in functionally constrained regions, 22% (twice as many as expected
      by chance) of genes harboring genotype-dependent DNA methylation exhibited allele
      specific gene expression as measured by RNA-seq of a lymphoblastoid cell line,
      indicating that some of these events are associated with gene expression
      differences. Overall, our results demonstrate that the influence of genotype on
      patterns of DNA methylation is widespread in the genome and greatly exceeds the
      influence of imprinting on genome-wide methylation patterns.

PMID- 21852960
TI  - Glutamine synthetase is a genetic determinant of cell type-specific glutamine
      independence in breast epithelia.
AB  - Although significant variations in the metabolic profiles exist among different
      cells, little is understood in terms of genetic regulations of such cell type
      specific metabolic phenotypes and nutrient requirements. While many cancer cells
      depend on exogenous glutamine for survival to justify the therapeutic targeting
      of glutamine metabolism, the mechanisms of glutamine dependence and likely
      response and resistance of such glutamine-targeting strategies among cancers are
      largely unknown. In this study, we have found a systematic variation in the
      glutamine dependence among breast tumor subtypes associated with mammary
      differentiation: basal- but not luminal-type breast cells are more glutamine
      dependent and may be susceptible to glutamine-targeting therapeutics. Glutamine
      independence of luminal-type cells is associated mechanistically with lineage
      specific expression of glutamine synthetase (GS). Luminal cells can also rescue
      basal cells in co-culture without glutamine, indicating a potential for glutamine
      symbiosis within breast ducts. The luminal-specific expression of GS is directly
      induced by GATA3 and represses glutaminase expression. Such distinct glutamine
      dependency and metabolic symbiosis is coupled with the acquisition of the GS and
      glutamine independence during the mammary differentiation program. Understanding
      the genetic circuitry governing distinct metabolic patterns is relevant to many
      symbiotic relationships among different cells and organisms. In addition, the
      ability of GS to predict patterns of glutamine metabolism and dependency among
      tumors is also crucial in the rational design and application of glutamine and
      other metabolic pathway targeted therapies.

PMID- 21852961
TI  - Ku must load directly onto the chromosome end in order to mediate its telomeric
      functions.
AB  - The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where
      it impacts several aspects of telomere structure and function. Although Ku avidly
      binds DNA ends via a preformed channel, its ability to associate with telomeres
      via this mechanism could be challenged by factors known to bind directly to the
      chromosome terminus. This has led to uncertainty as to whether Ku itself binds
      directly to telomeric ends and whether end association is crucial for Ku's
      telomeric functions. To address these questions, we constructed DNA end binding
      defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that
      were predicted to contact DNA. These mutants continued to associate with their
      known telomere-related partners, such as Sir4, a factor required for telomeric
      silencing, and TLC1, the RNA component of telomerase. Despite these interactions,
      we found that the Ku mutants had markedly reduced association with telomeric
      chromatin and null-like deficiencies for telomere end protection, length
      regulation, and silencing functions. In contrast to Ku null strains, the DNA end
      binding defective Ku mutants resulted in increased, rather than markedly
      decreased, imprecise end-joining proficiency at an induced double-strand break.
      This result further supports that it was the specific loss of Ku's telomere end
      binding that resulted in telomeric defects rather than global loss of Ku's
      functions. The extensive telomere defects observed in these mutants lead us to
      propose that Ku is an integral component of the terminal telomeric cap, where it
      promotes a specific architecture that is central to telomere function and
      maintenance.

PMID- 21852963
TI  - Pervasive sharing of genetic effects in autoimmune disease.
AB  - Genome-wide association (GWA) studies have identified numerous, replicable,
      genetic associations between common single nucleotide polymorphisms (SNPs) and
      risk of common autoimmune and inflammatory (immune-mediated) diseases, some of
      which are shared between two diseases. Along with epidemiological and clinical
      evidence, this suggests that some genetic risk factors may be shared across
      diseases-as is the case with alleles in the Major Histocompatibility Locus. In
      this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs
      in seven diseases: celiac disease, Crohn's disease, multiple sclerosis,
      psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1
      diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis
      (CPMA) which detects association of a SNP to multiple, but not necessarily all,
      phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease
      risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP
      wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are
      encoded near SNPs which predispose to the same subsets of diseases; we propose
      these as the mechanistic basis of shared disease risk. We are thus able to
      leverage genetic data across diseases to construct biological hypotheses about
      the underlying mechanism of pathogenesis.

PMID- 21852962
TI  - Celsr3 is required for normal development of GABA circuits in the inner retina.
AB  - The identity of the specific molecules required for the process of retinal
      circuitry formation is largely unknown. Here we report a newly identified
      zebrafish mutant in which the absence of the atypical cadherin, Celsr3, leads to
      a specific defect in the development of GABAergic signaling in the inner retina.
      This mutant lacks an optokinetic response (OKR), the ability to visually track
      rotating illuminated stripes, and develops a super-normal b-wave in the
      electroretinogram (ERG). We find that celsr3 mRNA is abundant in the amacrine and
      ganglion cells of the retina, however its loss does not affect synaptic
      lamination within the inner plexiform layer (IPL) or amacrine cell number. We
      localize the ERG defect pharmacologically to a late-stage disruption in GABAergic
      modulation of ON-bipolar cell pathway and find that the DNQX-sensitive fast b1
      component of the ERG is specifically affected in this mutant. Consistently, we
      find an increase in GABA receptors on mutant ON-bipolar terminals, providing a
      direct link between the observed physiological changes and alterations in GABA
      signaling components. Finally, using blastula transplantation, we show that the
      lack of an OKR is due, at least partially, to Celsr3-mediated defects within the
      brain. These findings support the previously postulated inner retina origin for
      the b1 component and reveal a new role for Celsr3 in the normal development of ON
      visual pathway circuitry in the inner retina.

PMID- 21852964
TI  - Bereavement among South African adolescents following a sibling's death from
      AIDS.
AB  - While increasing attention has been paid in recent years to studying the impact
      of parental death from AIDS on children, we know little about how a sibling's
      death from AIDS affects children. In this qualitative descriptive study, 11 in
      depth interviews were conducted by trained social workers with adolescents who
      had lost a sibling to AIDS, in KwaZulu-Natal Province, South Africa. The average
      time since the sibling's death was 18 months. These adolescents had been actively
      involved in caring for their sick sibling, yet they received inadequate emotional
      support from any source both before and after the sibling's death. HIV/AIDS
      stigma as well as the family's daily struggle to survive caused these adolescents
      to keep their feelings and their grief to themselves. Despite the trauma of
      losing a beloved sibling and the hardships of their environment, they
      demonstrated remarkable fortitude as well as concern for others. More research is
      needed on the issue of sibling bereavement associated with AIDS, and
      interventions that address the multiple needs of these vulnerable young people
      need to be developed.

PMID- 21852965
TI  - Imaging single photons and intrinsic optical signals for studies of vesicular and
      non-vesicular ATP release from axons.
AB  - The temporal and spatial dynamics of neurotransmitter release are fundamental to
      understanding activity-dependent signaling between axons and other cells,
      including neurons, glia, and vascular cells. A microscopic imaging technique is
      described that enables studying release of the neurotransmitter ATP from axons in
      response to action potentials. The method combines imaging single-photons,
      intrinsic optical signal imaging, and high magnification time-lapse microcopy to
      enable investigations of action potential-induced ATP release together with cell
      morphology and activity-dependent axon swelling. ATP released from axons
      catalyzes a chemiluminescent reaction between luciferin and luciferase that
      generates single photons that can be imaged individually. In addition to
      vesicular release, ATP release through membrane channels activated by axon
      swelling was monitored simultaneously with intrinsic optical signals. Repeated
      emissions of photons were observed from localized 15 MUm regions of axons, with a
      frequency distribution that differed from a normal distribution and from the
      frequency of emissions outside these localized regions.

PMID- 21852967
TI  - The sensory representation of time.

PMID- 21852966
TI  - Control of striatal signaling by g protein regulators.
AB  - Signaling via heterotrimeric G proteins plays a crucial role in modulating the
      responses of striatal neurons that ultimately shape core behaviors mediated by
      the basal ganglia circuitry, such as reward valuation, habit formation, and
      movement coordination. Activation of G protein-coupled receptors (GPCRs) by
      extracellular signals activates heterotrimeric G proteins by promoting the
      binding of GTP to their alpha subunits. G proteins exert their effects by
      influencing the activity of key effector proteins in this region, including ion
      channels, second messenger enzymes, and protein kinases. Striatal neurons express
      a staggering number of GPCRs whose activation results in the engagement of
      downstream signaling pathways and cellular responses with unique profiles but
      common molecular mechanisms. Studies over the last decade have revealed that the
      extent and duration of GPCR signaling are controlled by a conserved protein
      family named regulator of G protein signaling (RGS). RGS proteins accelerate GTP
      hydrolysis by the alpha subunits of G proteins, thus promoting deactivation of
      GPCR signaling. In this review, we discuss the progress made in understanding the
      roles of RGS proteins in controlling striatal G protein signaling and providing
      integration and selectivity of signal transmission. We review evidence on the
      formation of a macromolecular complex between RGS proteins and other components
      of striatal signaling pathways, their molecular regulatory mechanisms and impacts
      on GPCR signaling in the striatum obtained from biochemical studies and
      experiments involving genetic mouse models. Special emphasis is placed on RGS9-2,
      a member of the RGS family that is highly enriched in the striatum and plays
      critical roles in drug addiction and motor control.

PMID- 21852968
TI  - Cell signaling underlying epileptic behavior.
AB  - Epilepsy is a complex disease, characterized by the repeated occurrence of bursts
      of electrical activity (seizures) in specific brain areas. The behavioral outcome
      of seizure events strongly depends on the brain regions that are affected by
      overactivity. Here we review the intracellular signaling pathways involved in the
      generation of seizures in epileptogenic areas. Pathways activated by modulatory
      neurotransmitters (dopamine, norepinephrine, and serotonin), involving the
      activation of extracellular-regulated kinases and the induction of immediate
      early genes (IEGs) will be first discussed in relation to the occurrence of acute
      seizure events. Activation of IEGs has been proposed to lead to long-term
      molecular and behavioral responses induced by acute seizures. We also review
      deleterious consequences of seizure activity, focusing on the contribution of
      apoptosis-associated signaling pathways to the progression of the disease. A deep
      understanding of signaling pathways involved in both acute- and long-term
      responses to seizures continues to be crucial to unravel the origins of epileptic
      behaviors and ultimately identify novel therapeutic targets for the cure of
      epilepsy.

PMID- 21852969
TI  - In the blink of an eye: neural responses elicited to viewing the eye blinks of
      another individual.
AB  - Facial movements have the potential to be powerful social signals. Previous
      studies have shown that eye gaze changes and simple mouth movements can elicit
      robust neural responses, which can be altered as a function of potential social
      significance. Eye blinks are frequent events and are usually not deliberately
      communicative, yet blink rate is known to influence social perception. Here, we
      studied event-related potentials (ERPs) elicited to observing non-task relevant
      blinks, eye closure, and eye gaze changes in a centrally presented natural face
      stimulus. Our first hypothesis (H1) that blinks would produce robust ERPs (N170
      and later ERP components) was validated, suggesting that the brain may register
      and process all types of eye movement for potential social relevance. We also
      predicted an amplitude gradient for ERPs as a function of gaze change, relative
      to eye closure and then blinks (H2). H2 was only partly validated: large temporo
      occipital N170s to all eye change conditions were observed and did not
      significantly differ between blinks and other conditions. However, blinks
      elicited late ERPs that, although robust, were significantly smaller relative to
      gaze conditions. Our data indicate that small and task-irrelevant facial
      movements such as blinks are measurably registered by the observer's brain. This
      finding is suggestive of the potential social significance of blinks which, in
      turn, has implications for the study of social cognition and use of real-life
      social scenarios.

PMID- 21852970
TI  - Information diversity in structure and dynamics of simulated neuronal networks.
AB  - Neuronal networks exhibit a wide diversity of structures, which contributes to
      the diversity of the dynamics therein. The presented work applies an information
      theoretic framework to simultaneously analyze structure and dynamics in neuronal
      networks. Information diversity within the structure and dynamics of a neuronal
      network is studied using the normalized compression distance. To describe the
      structure, a scheme for generating distance-dependent networks with identical in
      degree distribution but variable strength of dependence on distance is presented.
      The resulting network structure classes possess differing path length and
      clustering coefficient distributions. In parallel, comparable realistic neuronal
      networks are generated with NETMORPH simulator and similar analysis is done on
      them. To describe the dynamics, network spike trains are simulated using
      different network structures and their bursting behaviors are analyzed. For the
      simulation of the network activity the Izhikevich model of spiking neurons is
      used together with the Tsodyks model of dynamical synapses. We show that the
      structure of the simulated neuronal networks affects the spontaneous bursting
      activity when measured with bursting frequency and a set of intraburst measures:
      the more locally connected networks produce more and longer bursts than the more
      random networks. The information diversity of the structure of a network is
      greatest in the most locally connected networks, smallest in random networks, and
      somewhere in between in the networks between order and disorder. As for the
      dynamics, the most locally connected networks and some of the in-between networks
      produce the most complex intraburst spike trains. The same result also holds for
      sparser of the two considered network densities in the case of full spike trains.

PMID- 21852971
TI  - Sustained activity in hierarchical modular neural networks: self-organized
      criticality and oscillations.
AB  - Cerebral cortical brain networks possess a number of conspicuous features of
      structure and dynamics. First, these networks have an intricate, non-random
      organization. In particular, they are structured in a hierarchical modular
      fashion, from large-scale regions of the whole brain, via cortical areas and area
      subcompartments organized as structural and functional maps to cortical columns,
      and finally circuits made up of individual neurons. Second, the networks display
      self-organized sustained activity, which is persistent in the absence of external
      stimuli. At the systems level, such activity is characterized by complex
      rhythmical oscillations over a broadband background, while at the cellular level,
      neuronal discharges have been observed to display avalanches, indicating that
      cortical networks are at the state of self-organized criticality (SOC). We
      explored the relationship between hierarchical neural network organization and
      sustained dynamics using large-scale network modeling. Previously, it was shown
      that sparse random networks with balanced excitation and inhibition can sustain
      neural activity without external stimulation. We found that a hierarchical
      modular architecture can generate sustained activity better than random networks.
      Moreover, the system can simultaneously support rhythmical oscillations and SOC,
      which are not present in the respective random networks. The mechanism underlying
      the sustained activity is that each dense module cannot sustain activity on its
      own, but displays SOC in the presence of weak perturbations. Therefore, the
      hierarchical modular networks provide the coupling among subsystems with SOC.
      These results imply that the hierarchical modular architecture of cortical
      networks plays an important role in shaping the ongoing spontaneous activity of
      the brain, potentially allowing the system to take advantage of both the
      sensitivity of critical states and the predictability and timing of oscillations
      for efficient information processing.

PMID- 21852972
TI  - Paraoxonase (PON1 and PON3) Polymorphisms: Impact on Liver Expression and
      Atorvastatin-Lactone Hydrolysis.
AB  - Atorvastatin delta-lactone, a major, pharmacologically inactive metabolite, has
      been associated with toxicity. In a previous study we showed that polymorphisms
      of UGT1A3 influence atorvastatin delta-lactone formation. Here we investigated
      the reverse reaction, atorvastatin delta-lactone hydrolysis, in a human liver
      bank. Screening of microarray data revealed paraoxonases PON1 and PON3 among 17
      candidate esterases. Microsomal delta-lactone hydrolysis was significantly
      correlated to PON1 and PON3 protein (r(s) = 0.60; r(s) = 0.62, respectively; P <
      0.0001). PON1 and PON3 were strongly correlated to each other (r(s) = 0.60) but
      PON1 was shown to be more extensively glycosylated than PON3. In addition a novel
      splice-variant of PON3 was identified. Genotyping of 40 polymorphisms within the
      PON-locus identified PON1 promoter polymorphisms (-108T > C, -832G > A, -1741G >
      A) and a tightly linked group of PON3 polymorphisms (-4984A > G, -4105G > A, 
      1091A > G, -746C > T, and F21F) to be associated with changes in atorvastatin
      delta-lactone hydrolysis and expression of PON1 but not PON3. However, carriers
      of the common PON1 polymorphisms L55M or Q192R showed no difference in delta
      lactone hydrolysis or PON expression. Haplotype analysis revealed decreased delta
      lactone hydrolysis in carriers of the most common haplotype *1 compared to
      carriers of haplotypes *2, *3, *4, and *7. Analysis of non-genetic factors showed
      association of hepatocellular and cholangiocellular carcinoma with decreased PON1
      and PON3 expression, respectively. Increased C-reactive protein and gamma
      glutamyl transferase levels were associated with decreased protein expression of
      both enzymes, and increased bilirubin levels, cholestasis, and presurgical
      exposure to omeprazole or pantoprazole were related to decreased PON3 protein. In
      conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic
      factors have an effect on PON1 and PON3 expression. This may influence response
      to therapy or adverse events in statin treatment.

PMID- 21852973
TI  - Morphine use in cancer surgery.
AB  - Morphine is the core of perioperative pain management. However, when it comes to
      cancer surgery the possibility that this drug might affect tumor recurrence and
      metastasis has raised concerns. The results of two recent retrospective clinical
      trials indicated that regional anesthesia/analgesia might be beneficial in
      prostate and breast cancer surgery. It was proposed that morphine could be
      responsible for the higher recurrence and mortality rate observed in the general
      anesthesia/opioid analgesia groups. Nevertheless, the results of several other
      retrospective studies and one randomized prospective trial failed to confirm any
      advantage for regional anesthesia/analgesia over general anesthesia and opioid
      analgesia. Moreover laboratory data on the effect of morphine on cancer are
      contradictory, ranging from tumor-promoting to anti-tumor effects. Considering
      that surgical stress and pain promote the recurrence and spread of cancer,
      choosing a proper analgesic strategy is of high significance. Although the
      question of whether morphine causes any harm to cancer patients remains
      unanswered, alternative analgesic regimens could be used concomitant to or
      instead of morphine to limit its potential adverse effects.

PMID- 21852974
TI  - Signalosomes in the brain: relevance in the development of certain
      neuropathologies such as Alzheimer's disease.
AB  - Emerging data suggest that compartmentalization of signaling molecules into
      particular membrane compartments, or lipid rafts, may be at the basis of numerous
      activities related to neuronal preservation against different pathologies. These
      signaling platforms (signalosomes) are formed by complex lipid and protein that
      may interact to develop a plethora of different physiological responses upon
      activation by different extracellular stimuli, thereby contributing to
      neuroprotection. One of the first studied signalosomes involved in
      neuroprotection against Alzheimer's disease (AD) is constituted by estrogen
      receptor (ER), in association with scaffolding caveolin-1 and a voltage-dependent
      anion channel (VDAC). In this complex, ER plays a neuroprotective role partially
      through the modulation of VDAC activation, a porin involved in amyloid-beta
      induced toxicity. Interestingly, ER and VDAC interactions appear to be altered in
      lipid rafts of AD brains, a phenomenon that may contribute to neuronal
      impairment. Alterations in lipid components of these subdomains may contribute to
      destabilization of this macrocomplex. These recent advances in the relevance of
      signaling platforms related to brain preservation, in particular against AD, are
      discussed in this work.

PMID- 21852975
TI  - Challenges in Fatty Acid and lipid physiology.

PMID- 21852976
TI  - The Serotonin Transporter Polymorphism (5-HTTLPR) and Alcohol Problems in Heavy
      Drinkers: Moderation by Depressive Symptoms.
AB  - Heavy alcohol use in young adults has been prospectively associated with a host
      of psychosocial and alcohol-related problems. Recent studies have supported the
      interaction between serotonin transporter polymorphism and adverse environmental
      factors, as a predictor of alcohol use and the development of alcohol dependence.
      The current study examined the role of depressive symptoms in combination with
      the serotonin transporter polymorphism as a predictor of alcohol use and alcohol
      related problems. Results revealed a significant genotype by depressive symptom
      interaction, such that heavier alcohol use was associated with depressive
      symptoms in L allele homozygotes but not among S allele carriers. These results
      remained significant after controlling for ethnicity and gender effects. These
      findings extend the emerging literature supporting 5-HTTLPR genotype as a risk
      factor for alcohol-related problems in the context of co-occurring symptoms of
      depression.

PMID- 21852977
TI  - Can ropinirole modulate reinforcing subjective effects of cocaine in humans?
AB  - In this study we evaluated, by means of the "cocaine rush visual analog scale,"
      the impact of ropinirole on the expected rush induced by cocaine in a group of
      heroin addicts abusing cocaine; the self-reported reaction to the rush blockade
      (if any) on cocaine consumption, and the correlations between this self-reported
      reaction and individual, clinical, and therapeutic parameters. Nineteen cocaine
      abuser heroin-dependent patients entered the study. Their experienced cocaine
      rush was 61.31 +/- 32.1% of the maximum effect previously experienced. Compared
      with their previous rush intensity 16 patients experienced significantly lower
      intensity, 3 the same intensity, and none a higher intensity. In particular, two
      patients experienced a complete blockade of rush and reported a reduced use of
      cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of
      these, nine reported they had reduced their use of cocaine. Ropinirole does
      diminish the subjective intensity of an expected cocaine rush, so interfering
      with the dynamics of reward, while supporting its possible use in the treatment
      of cocaine dependence.

PMID- 21852978
TI  - Physiological Signal Variability in hMT+ Reflects Performance on a Direction
      Discrimination Task.
AB  - Our ability to perceive visual motion is critically dependent on the human motion
      complex (hMT+) in the dorsal visual stream. Extensive electrophysiological
      research in the monkey equivalent of this region has demonstrated how neuronal
      populations code for properties such as speed and direction, and that neurometric
      functions relate to psychometric functions within the individual monkey. In
      humans, the physiological correlates of inter-individual perceptual differences
      are still largely unknown. To address this question, we used functional magnetic
      resonance imaging (fMRI) while participants viewed translational motion in
      different directions, and we measured thresholds for direction discrimination of
      moving stimuli in a separate psychophysics experiment. After determining hMT+ in
      each participant with a functional localizer, we were able to decode the
      different directions of visual motion from it using pattern classification (PC).
      We also characterized the variability of fMRI signal in hMT+ during stimulus and
      rest periods with a generative model. Relating perceptual performance to
      physiology, individual direction discrimination thresholds were significantly
      correlated with the variability measure in hMT+, but not with PC accuracies.
      Individual differences in PC accuracy were driven by non-physiological sources of
      noise, such as head-movement, which makes this method a poor tool to investigate
      inter-individual differences. In contrast, variability analysis of the fMRI
      signal was robust to non-physiological noise, and variability characteristics in
      hMT+ correlated with psychophysical thresholds in the individual participants.
      Higher levels of fMRI signal variability compared to rest correlated with lower
      discrimination thresholds. This result is in line with theories on stochastic
      resonance in the context of neuronal populations, which suggest that endogenous
      or exogenous noise can increase the sensitivity of neuronal populations to
      incoming signals.

PMID- 21852979
TI  - An Asymmetry in the Automatic Detection of the Presence or Absence of a Frequency
      Modulation within a Tone: A Mismatch Negativity Study.
AB  - The infrequent occurrence of a transient feature (deviance; e.g., frequency
      modulation, FM) in one of the regular occurring sinusoidal tones (standards)
      elicits the deviance related mismatch negativity (MMN) component of the event
      related brain potential. Based on a memory-based comparison, MMN reflects the
      mismatch between the representations of incoming and standard sounds. The present
      study investigated to what extent the infrequent exclusion of an FM is detected
      by the MMN system. For that purpose we measured MMN to deviances that either
      consisted of the exclusion or inclusion of an FM at an early or late position
      within the sound that was present or absent, respectively, in the standard.
      According to the information-content hypothesis, deviance detection relies on the
      difference in informational content of the deviant relative to that of the
      standard. As this difference between deviants with FM and standards without FM is
      the same as in the reversed case, comparable MMNs should be elicited to FM
      inclusions and exclusions. According to the feature-detector hypothesis, however,
      the deviance detection depends on the increased activation of feature detectors
      to additional sound features. Thus, rare exclusions of the FM should elicit no or
      smaller MMN than FM inclusions. In passive listening condition, MMN was obtained
      only for the early inclusion, but not for the exclusions nor for the late
      inclusion of an FM. This asymmetry in automatic deviance detection seems to
      partly reflect the contribution of feature detectors even though it cannot fully
      account for the missing MMN to late FM inclusions. Importantly, the behavioral
      deviance detection performance in the active listening condition did not reveal
      such an asymmetry, suggesting that the intentional detection of the deviants is
      based on the difference in informational content. On a more general level, the
      results partly support the "fresh-afferent" account or an extended memory
      comparison based account of MMN.

PMID- 21852980
TI  - Optic neuritis and retinal ganglion cell loss in a chronic murine model of
      multiple sclerosis.
AB  - Multiple sclerosis (MS) and its animal model experimental autoimmune
      encephalomyelitis (EAE) are neurodegenerative diseases with characteristic
      inflammatory demyelination in the central nervous system, including the optic
      nerve. Neuronal and axonal damage is considered to be the main cause of long-term
      disability in patients with MS. Neuronal loss, including retinal ganglion cell
      (RGC) apoptosis in eyes with optic neuritis (ON), also occurs in EAE. However,
      there is significant variability in the clinical course and level of neuronal
      damage in MS and EAE. The current studies examine the mechanisms and kinetics of
      RGC loss in C57/BL6 mice immunized with myelin oligodendrocyte glycoprotein to
      induce a chronic EAE disease. Clinical progression of EAE was scored daily and
      vision was assessed by optokinetic responses. At various time points, RGCs were
      counted and optic nerves were examined for inflammatory cell infiltration. Almost
      all EAE mice develop ON by day 15 post-immunization; however, RGC loss is delayed
      in these mice. No RGC loss is detected 25 days post-immunization, whereas RGC
      numbers in EAE mice significantly and progressively decrease compared to controls
      from 35 to 50 days post-immunization. The delayed time course of RGC loss is in
      stark contrast to that reported in relapsing EAE, as well as in rats with chronic
      EAE. Results suggest that different clinical disease courses of optic nerve
      inflammation may trigger distinct mechanisms of neuronal damage, or RGCs in
      different rodent strains may have variable resistance to neuronal degeneration.

PMID- 21852981
TI  - HURRICANE CHANGES: EXAMINING ENHANCED MOTIVATION TO CHANGE DRUG USING BEHAVIORS
      AMONG KATRINA EVACUEES.
AB  - Substance use disorders are credited with greater amounts of death and illness
      than all other preventable health problems. Billions of dollars are spent on
      efforts to control drug supplies and fund various treatment approaches, but
      relatively little resources have been directed towards investigating how
      environmental conditions can contribute to or detract from substance user's
      individual motivation to change behavior. Hurricane Katrina caused untold
      property damage and upheaval, in addition to the vast numbers of people whose
      lives it drastically affected. This article examines how surviving this ordeal,
      subsequent evacuation, and eventual resettlement in New Orleans or re-location to
      a different city (in this case, Houston) impacted individuals' motivation to
      change their substance use patterns and behaviors. This article's approach is
      grounded in the values of the social work profession and examines: 1) the role of
      life events in motivating change of substance using behaviors in the absence of
      formal treatment interventions; and 2) participant resilience in overcoming the
      adversities inherent to this disaster.

PMID- 21852983
TI  - Sensory processing problems in children with ADHD, a systematic review.
AB  - One of the most common psychiatric disorders in children is attention deficit
      hyperactivity disorder (ADHD). Its course and outcome are heterogeneous. Sensory
      processing problems impact the nature of response to daily events. ADHD and
      sensory problems may occur together and interact. No published review article
      about sensory processing problems in children with ADHD were found. A systematic
      search, conducted on Pub-Med (up to January 2010), and Google Scholar, yielded
      255 abstracts on sensory processing problems in children including 11 studies
      about sensory problems in children with ADHD. Sensory processing problems in
      children with ADHD is not a well studied area. Sensory processing problems in
      children with ADHD are more common than in typically developing children.
      Findings do not support that ADHD subtypes are distinct disorders with regard to
      sensory processing problems. However, co-morbidity with oppositional defiant
      disorder and anxiety are predictors of more severe sensory processing problems in
      children with ADHD.

PMID- 21852984
TI  - A comparison of comorbidity and psychological outcomes in children and
      adolescents with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: The purpose of this study was to compare psychiatric comorbid
      disorders and psychological outcomes in children and adolescents with Attention
      deficit/hyperactivity disorder (ADHD). METHODS: Subjects were divided into a
      child group (aged under 12 years) and an adolescent group (aged 12 years and
      above). All subjects were diagnosed with ADHD based on the DSM IV diagnostic
      criteria using the Kiddie-Schedule for Affective Disorders and Schizophrenia
      Present and Lifetime Korean Version (K-SADS-PL-K). The K-SADS-PL-K was also used
      to evaluate those psychiatric disorders comorbid with ADHD. And the Korean
      version of the Child Behavior Checklist (K-CBCL) was used to examine the
      subjects' psychological outcomes. RESULTS: The rate of comorbidity in adolescent
      group was significantly higher than that in the child group. In particular, the
      adolescent group had a significantly higher ratio of comorbid conduct disorder
      and mood disorder than the child group. With respect to the predominantly
      inattentive type and Not Otherwise Specified, the school subscale scores on the K
      CBCL for the children were significantly higher than those for the adolescents.
      CONCLUSION: These results suggest that the psychiatric comorbidity may differ
      between adolescents and children with ADHD. Therefore when treating adolescents
      with ADHD, more careful assessment and treatment targeting a range of
      comorbidities are needed.

PMID- 21852985
TI  - Relationship between Personality and Insomnia in Panic Disorder Patients.
AB  - OBJECTIVE: Panic disorder (PD) is frequently comorbid with insomnia, which could
      exacerbate panic symptoms and contribute to PD relapse. Research has suggested
      that characteristics are implicated in both PD and insomnia. However, there are
      no reports examining whether temperament and character affect insomnia in PD.
      Thus, we examined the relationship between insomnia and personality
      characteristics in PD patients. METHODS: Participants were 101 patients,
      recruited from 6 university hospitals in Korea, who met the DSM-IV-TR criteria
      for PD. We assessed sleep outcomes using the sleep items of 17-item Hamilton
      Depression Rating Scale (HAMD-17)(item 4=onset latency, item 5=middle awakening,
      and item 6=early awakening) and used the Cloninger's Temperament and Character
      Inventory-Revised-Short to assess personality characteristics. To examine the
      relationship between personality and insomnia, we used analysis of variance with
      age, sex, and severity of depression (total HAMD scores minus sum of the three
      sleep items) as the covariates. RESULTS: There were no statistical differences
      (p>0.1) in demographic and clinical data between patients with and without
      insomnia. Initial insomnia (delayed sleep onset) correlated to a high score on
      the temperamental dimension of novelty seeking 3 (NS3)(F(1,96)=6.93, p=0.03).
      There were no statistical differences (p>0.1) in NS3 between patients with and
      without middle or terminal insomnia. CONCLUSION: The present study suggests that
      higher NS3 is related to the development of initial insomnia in PD and that
      temperament and character should be considered when assessing sleep problems in
      PD patients.

PMID- 21852982
TI  - Schizophrenia, cancer and obstetric complications in an evolutionary perspective
      an empirically based hypothesis.
AB  - OBJECTIVE: Patients diagnosed with schizophrenia have reduced fecundity and
      premature mortality (both accidental and violent) with no obvious compensatory
      advantages among kin. The prevalence of the disorder is around 0.7/1%, higher
      than the expected prevalence of spontaneous mutations. Genes favoring
      schizophrenia may have been positively selected in the environment of
      evolutionary adaptation. Literature on potential adaptive genes is reviewed
      within an evolutionary framework. METHODS: Literature search on major scientific
      search engine (PubMed/Medline, Ovid/PsychInfo) on papers aimed at investigating
      potential pathways justifying a mutation-selection balanced model. Findings are
      presented with a narrative touch to favor readability and understanding. RESULTS:
      Reduced incidence of cancer in both patients diagnosed with schizophrenia and
      their siblings was reported worldwide. Such findings are notable given higher
      cancer risk factors in schizophrenia, i.e., smoking, alcohol abuse, obesity, poor
      diet, and poor adherence to therapy. Some genes involved in cancer proliferation
      might as well confer protective advantage in immune-surveillance, inflammation,
      vascular proliferation or apoptosis that otherwise will adversely affect early
      neurodevelopment. CONCLUSION: Evidence that reduced risk of certain somatic
      diseases is associated with schizophrenia is quite significant to progress in the
      evolutionary epidemiological analysis of psychopathology.

PMID- 21852986
TI  - The Effects of Social Skills Training vs. Psychoeducation on Negative Attitudes
      of Mothers of Persons with Schizophrenia: A Pilot Study.
AB  - OBJECTIVE: We compared the effects of two brief psychoeducation programs and
      social skills training on the negative attitudes of mothers with a son who has
      schizophrenia. METHODS: 15 mothers with strong negative feelings towards a sons
      with schizophrenia were assigned by convenience to participate in one of three
      brief (5 session) group programs at an outpatient clinic: lecture-based
      psychoeducation, video-based psychoeducation, or social skills training.
      Assessments using the Patient Rejection Scale were conducted with the mothers at
      post-treatment, and 3-, 6-, and 9-months later. RESULTS: Mothers in the three
      groups demonstrated significantly different patterns of changes in their negative
      attitudes following treatment. Whereas the mothers who received the two
      psychoeducation interventions showed reductions in rejecting attitudes
      immediately following the program, their scores gradually increased at the
      subsequent follow-up assessments. In contrast, the mothers in the social skills
      training group showed reductions in negative attitudes that were sustained across
      all of the follow-up assessments. CONCLUSION: Brief social skills training may be
      more effective than psychoeducation in reducing negative attitudes of parents who
      have an offspring with schizophrenia.

PMID- 21852987
TI  - Reliability and validity of the child and adolescent functioning impairment scale
      in children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: The purpose of the present study was to develop reliable and valid
      parent and teacher scales for measurement of functional impairment in children
      and adolescents in order to assist the diagnosis of attention
      deficit/hyperactivity disorder (ADHD). METHODS: Seventy-two children with ADHD
      fulfilling the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition
      criteria and forty-two normal controls were enrolled in this study. Parents and
      teachers of the subjects completed the parent and teacher form of the preliminary
      items of Child and Adolescent Functioning Impairment Scale (CAFIS) made up by the
      authors. Based on the reliability and factor analysis, the final parent (CAFIS
      parent form) and teacher version (CAFIS-teacher form) were constructed. Scales
      were analyzed for reliability and validity. Relative operating characteristics
      curve was drawn to calculate the cutoff scores of these scales for children with
      ADHD. RESULTS: The CAFIS-parent and CAFIS-teacher forms consist of four and three
      factors, respectively. Internal consistency and test-retest correlation of the
      scales were satisfactory. The CAFIS and Children's Global Assessment Scale were
      significantly correlated. All scores of subscales of CAFIS in ADHD group were
      significantly higher than those of control group. The sensitivity and specificity
      of the subscales were mostly at an appropriate level. CONCLUSION: The CAFIS is a
      brief layperson-administered scale to assess functional impairment of children
      and adolescents. It can be a useful tool for parents and teachers to objectively
      measure the functions of children at home and in school. This scale was found to
      be reliable and valid, and it appears to be a valuable instrument in Korean
      language.

PMID- 21852988
TI  - Do defense styles of ego relate to volumes of orbito-frontal cortex in patients
      with obsessive-compulsive disorder?
AB  - OBJECTIVE: Although the importance of orbito-frontal cortex (OFC) is established
      in the pathogenesis of obsessive compulsive disorder (OCD), no study have
      evaluated its relation to the traditional psychodynamic perspective. In the
      present study, we aimed to evaluate the relationship between the defense styles
      consisting of mature, immature and neurotic defenses and OFC volumes of patients
      with OCD. METHODS: Subjects were selected among those of our previous study, and
      so eighteen patients with OCD and same number of healthy controls were took into
      the study. The patients and controls had underwent magnetic resonance imaging
      (MRI). In addition, the Defense Style Questionnaire-40 was administered to obtain
      defense styles of patients and controls. RESULTS: No significant relationship was
      found between the right OFC volumes of both the patient and control groups and
      their scores of mature, neurotic, or immature defense mechanisms. As for the left
      OFC volumes, the only significant relationship for the scores of immature defense
      mechanism was found in the patient group. CONCLUSION: The results of the present
      study indicated that there was no significant relationship between OFC volumes of
      the patient group and their scores of mature, neurotic, or immature defense
      mechanisms, except a significant relation with the scores of immature defense
      mechanisms.

PMID- 21852989
TI  - Epigenetic changes of serotonin transporter in the patients with alcohol
      dependence: methylation of an serotonin transporter promoter CpG island.
AB  - OBJECTIVE: Psychiatric disorders such as depression, anxiety and alcohol
      dependence are associated with serotonin metabolism. We assessed the methylation
      level of the serotonin transporter (5-HTT) promoter region in control and alcohol
      dependent patients. METHODS: Twenty seven male patients who met the Diagnostic
      and Statistical Manual of Mental Disorder IV (DSM-IV) criteria for alcohol
      dependence were compared with fifteen controls. Polymerase chain reaction (PCR)
      assays of bisulfate-modified DNA were designed to amplify a part of the CpG
      island in the 5HTT gene. Pyrosequencing was performed and the methylation level
      at seven CpG island sites was measured. RESULTS: We found no differences in the
      methylation patterns of the serotonin transporter linked promoter region (5
      HTTLPR) between alcohol-dependent and control subjects. CONCLUSION: Our negative
      finding may be because 5-HTT epigenetic variation may not affect the expression
      for 5-HTT or there may be other methylation site critical for its expression. To
      find out more conclusive result, repeating the study in more methylation sites
      with a larger number of samples in a well-controlled setting is needed.

PMID- 21852990
TI  - Serum homocysteine and folate levels in korean schizophrenic patients.
AB  - OBJECTIVE: This study was conducted to confirm the results of the authors'
      previous research on schizophrenia manifesting high serum homocysteine and low
      folate levels. This study is anchored on a theory that a high serum homocysteine
      concentration affects schizophrenia by virtue of a neurotoxic mechanism, and on a
      report that some schizophrenia patients with high homocysteine levels benefited
      from high folate ingestion. METHODS: The serum homocysteine, folate, and vitamin
      B(12) levels of 236 normal-control-group subjects and 234 schizophrenia subjects
      who met the diagnostic criteria based on DSM-IV-TR were compared. The
      homocysteine levels were measured via fluorescence polarization immunoassay, and
      the folate and vitamin B(12) levels were determined via radioimmunoassay.
      RESULTS: The homocysteine levels of the patient group were significantly higher
      than those of the normal control group. The homocysteine level was more
      negatively correlated with the folate level in the schizophrenia group than in
      the control group. The percentages of female and male schizophrenia subjects
      manifesting high homocysteine levels were 33.8 and 51.5%, respectively. The
      percentage of schizophrenia subjects with low folate levels was 66.2%. In the low
      and normal-folate-level groups, the patient group showed significantly higher
      homocysteine levels than the normal control group. The low-folate-level patient
      group particularly showed significantly higher homocysteine levels than the low
      folate-level normal control group. CONCLUSION: Some schizophrenia patients with
      high serum homocysteine levels may have the genetic defect of having low folate
      serum levels. In such cases, folate ingestion may be a good management modality
      for clinical improvement.

PMID- 21852991
TI  - A randomized, open-label assessment of response to various doses of atomoxetine
      in korean pediatric outpatients with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: This multicenter, randomized, open-label, parallel trial aimed to
      provide a detailed dose-response profile for atomoxetine in Korean pediatric
      outpatients with attention-deficit/hyperactivity disorder (ADHD). METHODS: Male
      and female outpatients aged 6-18 years with ADHD meeting symptom severity
      criteria of 1.5 standard deviations above age and gender norms on the ADHD Rating
      Scale-IV-Parent: Investigator-Administered and Scored (ADHDRS-IV-Parent: Inv),
      and a Clinical Global Impression-ADHD-Severity score >=4 were randomized to
      atomoxetine (mg/kg/day) 0.2 fixed, 0.5 fixed or 0.5 (7 days), 0.8 (7 days) then
      1.2 for 28 days. The primary efficacy measure was change in ADHDRS-IV-Parent: Inv
      total score after 6 weeks of atomoxetine treatment. RESULTS: Of 153 randomized
      patients, 83.7% were male and mean age was 9.8 (SD+/-2.4) years. The completion
      rate was 86.9%. A graded dose response was apparent with mean change in ADHDRS-IV
      Parent: Inv total scores of -9.6, -12.3 and -14.5 with atomoxetine 0.2, 0.5 and
      1.2 mg/kg/day, respectively (p=0.024 - F-test). Moreover, a greater reduction in
      ADHD symptoms, as assessed by mean change from baseline to endpoint CGI-S and
      mean CGI-ADHD-Improvement at endpoint, was also observed with increasing
      atomoxetine dose. More patients receiving atomoxetine 1.2 mg/kg/day reported >=1
      treatment-emergent adverse event/s (58.3%) compared with 0.5 (40.7%; p=0.11) or
      0.2 mg/kg/day (29.4%; p=0.005). These were generally mild to moderate.
      CONCLUSION: Atomoxetine was found to be safe and well tolerated at all doses
      administered in Korean pediatric ADHD patients, and 1.2 mg/kg/day was an
      efficacious dose in this population.

PMID- 21852992
TI  - The changes of blood glucose control and lipid profiles after short-term smoking
      cessation in healthy males.
AB  - OBJECTIVE: Our aim was to evaluate the changes in blood glucose control and lipid
      profiles after 2-months of smoking cessation in healthy males. METHODS: Smoking
      abstinence was evaluated through self-report and urine cotinine levels. 12
      individuals who succeeded in quitting smoking were analyzed. Fasting values of
      glucose and insulin were used to estimate the beta-cell activity and insulin
      resistance was evaluated using the Homeostasis Model Assessment (HOMA) and
      Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: The data showed
      that the subjects had a significant increase in weight, body mass index and
      fasting plasma glucose levels after smoking cessation. The HOMA-Insulin
      Resistance and the HOMA beta-cell function increased significantly (p=0.005,
      p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In
      addition, the low-density lipoprotein cholesterol levels decreased significantly
      (p=0.028); however, changes in the high-density lipoprotein cholesterol, the
      triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445
      respectively). CONCLUSION: During the initial stage of smoking abstinence,
      insulin resistance increased and insulin sensitivity decreased due to elevated
      body weight and fat composition. Therefore, it is important to educate
      individuals that stop smoking about the necessity of weight control during
      smoking cessation programs.

PMID- 21852993
TI  - The effect of repeated virtual nicotine cue exposure therapy on the
      psychophysiological responses: a preliminary study.
AB  - OBJECTIVE: Smoking related cues may elicit smoking urges and psychophysiological
      responses in subjects with nicotine dependence. This study aimed to investigate
      the effect of repeated virtual cue exposure therapy using the surround-screen
      based projection wall system on the psychophysiological responses in nicotine
      dependence. METHODS: The authors developed 3-dimensional neutral and smoking
      related environments using virtual reality (VR) technology. Smoking-related
      environment was a virtual bar, which comprised both object-related and social
      situation cues. Ten subjects with nicotine dependence participated in 4-week (one
      session per week) virtual cue exposure therapy. Psychophysiological responses
      [electromyography (EMG), skin conductance (SC), and heart rate] and subjective
      nicotine craving were acquired during each session. RESULTS: VR nicotine cue
      elicited greater psychophysiological responses and subjective craving for smoking
      than did neutral cue, and exposure to social situation cues showed greater
      psychophysiological responses in SC and EMG than did object-related cues. This
      responsiveness decreased during the course of repeated therapy. CONCLUSION: The
      present study found that both psychophysiological responses and subjective
      nicotine craving were greater to nicotine cue exposure via projection wall VR
      system than to neutral cues and that enhanced cue reactivity decreased gradually
      over the course of repeated exposure therapy. These results suggest that VR cue
      exposure therapy combined with psychophysiological response monitoring may be an
      alternative treatment modality for smoking cessation, although the current
      findings are preliminary.

PMID- 21852994
TI  - Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells.
AB  - OBJECTIVE: To analyze both differentially expressed genes and the Bcl-xL protein
      expression after acute and chronic treatment with fluoxetine in rat C6 glioma
      cells. METHODS: C6 glioma cells were cultured for 24 h or 72 h after treatment
      with 10 uM fluoxetine, and gene expression patterns were observed using
      microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h
      after treatment with 10 uM fluoxetine, and the expression of Bcl-xL protein was
      measured using western blot. RESULTS: As determined by microarray, treatment with
      fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down
      regulated 7 genes (including cyclin G-associated kinase). Treatment with
      fluoxetine for 72 h up-regulated 53 genes (including Gsalpha and Bcl-xL) and down
      regulated 77 genes (including Galphai2 and annexin V). Based on the qRT-PCR
      results, there was an increase in Gsalpha mRNA and a decrease in Galphai2 mRNA at
      72 h in fluoxetine-treated cells as compared to control, a result that was
      consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at
      24 h and at 72 h) in fluoxetine-treated cells as compared to control,
      demonstrating a tendency to increase gradually. Bcl-xL protein expression
      increased as the duration of fluoxetine treatment increased. CONCLUSION: These
      results suggest that chronic treatment with fluoxetine not only initiates the
      cAMP pathway through inducing Gsalpha expression but also induces Bcl-xL
      expression, thus inhibiting apoptosis.

PMID- 21852995
TI  - Co-administration of subeffective anxiolytic doses of diazepam and hydroxyzine in
      elevated zero-maze in mice.
AB  - OBJECTIVE: Benzodiazepines are from the most common drugs which are used for
      treatment of anxiety disorders. There are other drugs with antianxiety properties
      including antihistamines such as hydroxyzine, too. Body of evidence show that co
      administration of two drugs which act through different mechanisms, makes the
      dose of each drug to be reduced, while preserving the desired effect with less
      adverse drug reactions. The aim of this study was to see whether co
      administration of subeffective antianxiety doses of diazepam and hydroxyzine has
      any antianxiety effect in elevated zero-maze (EZM) in mice. METHODS: To find the
      highest subeffective dose of each drug, different doses of hydroxyzine from 1.5
      to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male
      mice. Thirty minutes later, the animals were placed on EZM and various parameters
      of anxiety were recorded by a camera to assess later. After determination of
      subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and
      diazepam was done and the anxiety parameters were measured. RESULTS: In co
      administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as
      subeffective antianxiety doses of either drug, there were not any significant
      differences in main anxiety parameters, i.e., time spent in open areas and open
      area entries compared to control group. Hence, no anxiolytic effect was seen.
      CONCLUSION: It seems that subeffective doses of diazepam and hydroxyzine may not
      have any facilitating or synergistic effect on each other in antianxiety
      responses in mice.

PMID- 21852996
TI  - A case of catatonia and neuroleptic malignant syndrome probably associated with
      antipsychotic in Korea.
AB  - Several studies have reported on catatonia caused by the use of antipsychotic
      drugs and on the association between catatonia and neuroleptic malignant syndrome
      (NMS), but none has reported such a case in Korea. Here, we report the case of a
      20-year-old woman whose catatonia and NMS appeared associated with the
      administration of an atypical antipsychotic drug. We discuss the association
      between NMS and catatonia due to neuroleptic use.

PMID- 21852997
TI  - High-content screening in microfluidic devices.
AB  - IMPORTANCE OF THE FIELD: Miniaturization is the key to advancing the state of the
      art in high-content screening (HCS) in order to enable dramatic cost savings
      through reduced usage of expensive biochemical reagents and to enable large-scale
      screening on primary cells. Microfluidic technology offers the potential to
      enable HCS to be performed with an unprecedented degree of miniaturization. AREAS
      COVERED IN THIS REVIEW: This perspective highlights a real-world example from the
      authors' work of HCS assays implemented in a highly miniaturized microfluidic
      format. The advantages of this technology are discussed, including cost savings,
      high-throughput screening on primary cells, improved accuracy, the ability to
      study complex time-varying stimuli, and ease of automation, integration and
      scaling. WHAT THE READER WILL GAIN: The reader will understand the capabilities
      of anew microfluidics-based platform for HCS and the advantages it provides over
      conventional plate-based HCS. TAKE HOME MESSAGE: Microfluidics technology will
      drive significant advancements and broader usage and applicability of HCS in drug
      discovery.

PMID- 21852998
TI  - A case of rapid-growing anaplastic meningiomas.
AB  - Meningiomas are tumours originating from the leptomeningeal covering of the brain
      and spinal cord and are generally benign and slow growing. Rarely, they show
      malignant anaplastic characteristics with a high recurrence rate. A number of
      factors have been reported to predict this high recurrence. Such factors are
      histopathological ones, such as necrosis and hypercellularity, the World Health
      Organization (WHO) grade, mitotic index, positivity of proliferation markers (Ki
      67 or MIB-1), clinical parameters such as age, gender, localisation, cytogenetic
      factors and radiation treatment. The present case reports a patient with a giant
      meningioma over the right frontal lobe who had almost all possible negative
      prognostic parameters and showed an explosive multifocal recurrence in a timespan
      of about 5 months.

PMID- 21852999
TI  - Cerebral neuroschistosomiasis: a rare clinical presentation and review of the
      literature.
AB  - The symptomatic presentation of cerebral schistosomiasis is uncommon. The case of
      a 25-year-old woman from Equatorial Guinea with headache and seizures secondary
      to cerebral neuroschistosomiasis, as confirmed by histopathological examination
      and microbiological study, is presented. A review of the literature on this
      subject is also provided.

PMID- 21853000
TI  - Association between sarcoidosis and Behcet disease in a young woman with symptoms
      mimicking myasthaenia gravis.
AB  - The present report concerns a young woman with long-standing Behcet disease (BD),
      who developed sarcoidosis and myasthaenia gravis (MG)-like syndrome. Although an
      itching sensation after intravenous methylprednisolone made treatment more
      difficult, low-dose oral methylprednisolone, thalidomide and ciclosporin A
      relieved the chronic granulomatous inflammation and pyridostigmine controlled the
      ptosis.

PMID- 21853001
TI  - Hemichorea with antiphospholipid antibodies in a patient with systemic lupus
      erythematosus.
AB  - We present a report of a patient with systemic lupus erythematosus who
      subsequently developed hemichorea associated with increased anti-phospholipid
      antibodies values.

PMID- 21853002
TI  - A novel germline mutation of the VHL gene in a Greek family with Von Hippel
      Lindau disease.
AB  - Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder, caused by
      mutations of the VHL gene showing a strong genotype-phenotype correlation. The
      present report concerns a 16-year-old girl with VHL (retinal, spinal cord and
      cerebellar haemangioblastomas and pancreatic cysts), her father (retinal and
      spinal cord haemangioblastomas) and the phenotypically healthy mother and younger
      brother and sister. DNA extraction, PCR and direct sequencing of the VHL entire
      coding and intronic flanking sequences, were performed according to standard
      procedures. In the index patient and her father a novel heterozygous germline was
      identified; nonsense mutation (p.145X) in exon 2 of VHL, leading to a truncated
      VHL protein lacking the last 66 amino acids. This is the first report of a novel
      VHL mutation in patients with VHL associated with haemangioblastomas and
      pancreatic cysts but not renal cell carcinoma.

PMID- 21853003
TI  - Barotraumatic perforation of the pharyngo-oesophagus secondary to a Lambrini
      "bottle explosion".
AB  - An interesting case of a middle-aged woman who sustained oral lacerations and
      pharyngeal tear/perforation on opening a bottle of Lambrini sparkling wine with
      her teeth is presented. The patient presented to the Accident and Emergency (A&E)
      department with bleeding from the mouth and dyspnoea, and on examination had a
      neck surgical emphysema and visible laceration to the oropharynx. On further
      investigation, including a range of imaging modalities, a diagnosis of pharyngeal
      tear/perforation was made, detected on a gastrograffin swallow test. The patient
      was subsequently treated conservatively, being kept nil by mouth and fed through
      a nasogastric tube, with prophylactic antibiotic cover. The patient was re-imaged
      1 week later, which displayed complete resolution of the tear, and was
      subsequently discharged on a normal oral diet.

PMID- 21853004
TI  - Hydropericardium prevented diagnosis of constrictive pericarditis: an unusual
      case of Rosai-Dorfman disease.
AB  - The present report concerns an unusual case of extranodal Rosai-Dorfman disease
      involving the epicardium, mesenterium, pleural cavity and lung. All involved
      lesions showed characteristics of S100-positive histiocytes exhibiting
      emperipolesis. The patient was a 51-year-old woman with a 2-year evolution of
      chest distress, dyspnoea and oedema. Pathological examination indicated that
      heart failure, which resulted from constrictive pericarditis, led to the fatal
      outcome of this case. Interference from severe hydropericardium prevented timely
      diagnosis and appropriate treatment. Therefore it is recommend that, despite
      being a rare condition, pericardium-involved Rosai-Dorfman disease should be
      taken into consideration in differential diagnoses, especially in cases of severe
      hydropericardium.

PMID- 21853005
TI  - Spinal tuberculoma in pregnancy: a rare cause of back pain.

PMID- 21853006
TI  - Meningomyelocele: the tip of the iceberg.
AB  - Meningomyelocele is one of the commonest neural tube closure defects. A 2-month
      old girl presented with meningomyelocele in the lumbosacral region that had been
      present since birth. She had experienced paraparesis for 1 month. Terminally, she
      had excessive crying, and died within 1 week of presentation. An autopsy revealed
      focally infected meningomyelocele with features of Arnold-Chiari II malformation.
      Associated malformations included polymicrogyria, neuronal heterotopias and
      neuronal cytomegaly in the brainstem. Cortical malformations may be detected
      radiologically, thus prompting surgical intervention and reduced mortality. By
      contrast, the presence of cytomegaly may hinder postsurgical improvement,
      affecting intellectual outcome in survivors in particular. New genetic
      revelations also offer a scope for genetic counselling in these conditions.

PMID- 21853007
TI  - An unusual case of malignant thymoma associated graft-versus-host disease.
AB  - A woman in her early 50s presented with recurrent severe chest infections.
      Investigations revealed a low white cell count and a diagnosis of autoimmune
      neutropenia was made. Subsequently, an infiltrating thymic tumour (mitoses only)
      in the absence of myasthenia gravis was found. She underwent radical surgery.
      When neutropenic, she complained of painful, swollen joints and soft tissues. She
      was started on steroids and immunosuppressants and her pain settled. The
      following year, she had local malignant recurrence confirmed on imaging. She
      declined chemotherapy or targeted somatostatin and opted for alternative
      therapies. She developed a microcytic anaemia and commenced erythropoietin. This
      coincided with the development of a painful expanded rib lesion, hypercalcaemia,
      and ascites. She remained unwell with periodical flares in disease affecting many
      different organs and continued to mount a significant immunological response to
      her thymic tumour, manifesting as biopsy proven graft-versus-host disease
      involving joints, skin and lungs. This has been a complex clinical case involving
      multiple specialities, including haematology, oncology, immunology, endocrinology
      and palliative medicine.

PMID- 21853008
TI  - Chronic lymphocytic leukaemia, dyspnoea and "tree-in-bud" sign on chest CT scan.
AB  - Chronic lymphocytic leukaemia (CLL) is a common disorder. Patients typically
      present with lymphadenopathy, splenomegaly and marked lymphocytosis (often >100
      000/MUl). Although pulmonary involvement from CLL can be found in more than one
      third of patients on autopsy, respiratory symptoms caused by the disease itself
      are not often reported. Pulmonary involvement mainly includes parenchymal
      infiltrates, peribronchial and perivascular infiltration, recurrent bacterial
      pneumonia, oedema or infarction, pleural effusions, and lymphadenopathy.
      Occasionally, patients may present with dry cough and progressive dyspnoea, even
      with low peripheral white blood cell count. We report a case of CLL and dyspnoea
      at rest, predominant "tree-in-bud" sign on chest computed tomography scan, and
      biopsy proven bronchiolar infiltration with monoclonal lymphocytes. With
      bronchoalveolar lavage alone, the diagnosis would have been missed. Chemotherapy
      with rituximab, cyclophosphamide, and fludarabinphosphate led to a prompt
      clinical and radiological improvement with a gain in 6 min walking distance from
      60 to 210 m.

PMID- 21853009
TI  - Fatal intra-abdominal haemorrhage following percutaneous endoscopic gastrostomy.
AB  - An 83-year-old man was admitted to hospital with a general decline in health,
      including deteriorating ability to swallow. He was not managing sufficient oral
      intake to meet his daily nutritional requirements, so had a percutaneous
      endoscopic gastrostomy (PEG) tube inserted for long-term feeding. Following the
      procedure he became shocked, and was unresponsive to aggressive fluid
      resuscitation. He died approximately 7 h after the PEG tube insertion. A
      postmortem examination revealed 2.5 litres of blood and bloodstained fluid within
      the abdominal cavity and a haemorrhagic pancreas. Microscopy of the pancreas
      showed a defect in a small to medium-sized artery, likely to be a branch of the
      splenic artery. The cause of death (as per section 1 of the death certificate)
      was (1a) intra-abdominal haemorrhage, (1b) pancreatic trauma at PEG feeding tube
      insertion and (1c) dysphagia due to cerebrovascular disease.

PMID- 21853010
TI  - Ascending myelitis.

PMID- 21853011
TI  - Recurrent pulmonary and cerebral thromboembolism in an adult patients following
      incomplete removal of ventriculoatrial shunt for congenital hydrocephalus.
AB  - A 34-year-old man was admitted to our hospital's department of neurology because
      he had experienced a cryptogenic stroke followed by a transient ischaemic attack.
      The patient suffered from congenital hydrocephalus which was treated by
      ventriculoatrial shunt at 8 months of age. Twelve months later, because of
      recurrent infections, the catheter was partially removed and the distal segment
      was left in place. At admission, the transoesophageal echocardiogram showed
      severe pulmonary hypertension (80 mm Hg confirmed by invasive measurement). The
      distal tip of the catheter had migrated into the left atrium through a patent
      foramen ovale inducing a massive right-to-left shunt. We surgically removed the
      catheter and closed the interatrial defect. At 1 and 6 months follow-up the
      patient was asymptomatic with a reduced pulmonary hypertension (50 mm Hg). Since
      there was no other clinical finding responsible for the recurrent thromboembolic
      events, both at the pulmonary and cerebral level, the catheter was removed to
      prevent further complications.

PMID- 21853012
TI  - Exercise and Cancer-related Fatigue.
AB  - Cancer-related fatigue is the most common side effect reported by cancer patients
      during and after treatment. Cancer-related fatigue significantly interferes with
      a patient's ability to perform activities of daily living and maintain functional
      independence and quality of life. Cancer-related fatigue can also interfere with
      a patient's ability to complete treatments. The purpose of this article is to
      provide an overview of cancer-related fatigue, its pathopsychophysiology, and the
      role of exercise in the management of this side effect.

PMID- 21853013
TI  - Combination antibiotics for the treatment of Chlamydia-induced reactive
      arthritis: is a cure in sight?
AB  - The inflammatory arthritis that develops in some patients subsequent to
      urogenital infection by the obligate intracellular bacterial pathogen Chlamydia
      trachomatis, and that induced subsequent to pulmonary infection with C.
      pneumoniae, both have proved difficult to treat in either their acute or chronic
      forms. Over the last two decades, molecular genetic and other studies of these
      pathogens have provided a good deal of information regarding their metabolic and
      genetic structures, as well as the detailed means by which they interact with
      their host cells. In turn, these insights have provided for the first time a
      window into the bases for treatment failures for the inflammatory arthritis. In
      this article we discuss the biological bases for those treatment failures,
      provide suggestions as to research directions that should allow improvement in
      treatment modalities, and speculate on how treatment regimens that currently show
      promise might be significantly improved over the near future using
      nanotechological means.

PMID- 21853014
TI  - A branching process model for flow cytometry and budding index measurements in
      cell synchrony experiments.
AB  - We present a flexible branching process model for cell population dynamics in
      synchrony/time-series experiments used to study important cellular processes. Its
      formulation is constructive, based on an accounting of the unique cohorts in the
      population as they arise and evolve over time, allowing it to be written in
      closed form. The model can attribute effects to subsets of the population,
      providing flexibility not available using the models historically applied to
      these populations. It provides a tool for in silico synchronization of the
      population and can be used to deconvolve population-level experimental
      measurements, such as temporal expression profiles. It also allows for the direct
      comparison of assay measurements made from multiple experiments. The model can be
      fit either to budding index or DNA content measurements, or both, and is easily
      adaptable to new forms of data. The ability to use DNA content data makes the
      model applicable to almost any organism. We describe the model and illustrate its
      utility and flexibility in a study of cell cycle progression in the yeast
      Saccharomyces cerevisiae.

PMID- 21853015
TI  - A bivariate space-time downscaler under space and time misalignment.
AB  - Ozone and particulate matter PM(2.5) are co-pollutants that have long been
      associated with increased public health risks. Information on concentration
      levels for both pollutants come from two sources: monitoring sites and output
      from complex numerical models that produce concentration surfaces over large
      spatial regions. In this paper, we offer a fully-model based approach for fusing
      these two sources of information for the pair of co-pollutants which is
      computationally feasible over large spatial regions and long periods of time. Due
      to the association between concentration levels of the two environmental
      contaminants, it is expected that information regarding one will help to improve
      prediction of the other. Misalignment is an obvious issue since the monitoring
      networks for the two contaminants only partly intersect and because the
      collection rate for PM(2.5) is typically less frequent than that for
      ozone.Extending previous work in Berrocal et al. (2009), we introduce a bivariate
      downscaler that provides a flexible class of bivariate space-time assimilation
      models. We discuss computational issues for model fitting and analyze a dataset
      for ozone and PM(2.5) for the ozone season during year 2002. We show a modest
      improvement in predictive performance, not surprising in a setting where we can
      anticipate only a small gain.

PMID- 21853016
TI  - Characterization of 14-3-3 proteins from Cryptosporidium parvum.
AB  - The parasite Cryptosporidium parvum has three 14-3-3 proteins: Cp14epsilon, Cp14a
      and Cp14b, with only Cp14epsilon similar to human 14-3-3 proteins in sequence,
      peptide-binding properties and structure. Structurally, Cp14a features the
      classical 14-3-3 dimer but with a uniquely wide pocket and a disoriented RRY
      triad potentially incapable of binding phosphopeptides. The Cp14b protein
      deviates from the norm significantly: (i) In one subunit, the phosphorylated C
      terminal tail is bound in the binding groove like a phosphopeptide. This supports
      our binding study indicating this protein was stabilized by a peptide mimicking
      its last six residues. (ii) The other subunit has eight helices instead of nine,
      with alphaA and alphaB forming a single helix and occluding the peptide-binding
      cleft. (iii) The protein forms a degenerate dimer with the two binding grooves
      divided and facing opposite directions. These features conspire to block and
      disrupt the bicameral substrate-binding pocket, suggesting a possible tripartite
      auto-regulation mechanism that has not been observed previously. ENHANCED
      VERSION: This article can also be viewed as an enhanced version in which the text
      of the article is integrated with interactive 3D representations and animated
      transitions. Please note that a web plugin is required to access this enhanced
      functionality. Instructions for the installation and use of the web plugin are
      available in Text S1.

PMID- 21853017
TI  - Polyphasic analysis of intraspecific diversity in Epicoccum nigrum warrants
      reclassification into separate species.
AB  - BACKGROUND: Epicoccum nigrum Link (syn. E. purpurascens Ehrenb. ex Schlecht) is a
      saprophytic ascomycete distributed worldwide which colonizes a myriad of
      substrates. This fungus has been known as a biological control agent for plant
      pathogens and produces a variety of secondary metabolites with important
      biological activities as well as biotechnological application. E. nigrum produces
      darkly pigmented muriform conidia on short conidiophores on sporodochia and is a
      genotypically and phenotypically highly variable species. Since different
      isolates identified as E. nigrum have been evaluated as biological control agents
      and used for biocompound production, it is highly desirable that this species
      name refers to only one lineage. However, according to morphological and genetic
      variation, E. nigrum present two genotypes that may comprise more than one
      species. METHODOLOGY/PRINCIPAL FINDINGS: We report the application of combined
      molecular (ITS and beta-tubulin gene sequence analysis, PCR-RFLP and AFLP
      techniques), morphometric, physiological, genetic compatibility and recombination
      analysis to study the taxonomic relationships within an endophytic population
      that has been identified as E. nigrum. This combined analysis established two
      genotypes showing morphological, physiological and genetic divergence as well as
      genetic incompatibility characterized by colony inhibition, strongly indicating
      that these genotypes correspond to different species. Genotype 1 corresponds to
      E. nigrum while genotype 2 represents a new species, referred to in this study as
      Epicoccum sp. CONCLUSIONS/SIGNIFICANCE: This research contributes to the
      knowledge of the Epicoccum genus and asserts that the classification of E. nigrum
      as a single variable species should be reassessed. In fact, based on the
      polyphasic approach we suggest the occurrence of cryptic species within E. nigrum
      and also that many of the sequences deposited as E. nigrum in GenBank and culture
      collection of microbial strains should be reclassified, including the reference
      strain CBS 161.73 sequenced in this work. In addition, this study provides
      valuable tools for differentiation of Epicoccum species.

PMID- 21853019
TI  - Statistical power and estimation of incidence rate ratios obtained from BED
      incidence testing for evaluating HIV interventions among young people.
AB  - BACKGROUND: The objectives of this study were to determine the capacity of BED
      incidence testing to a) estimate the effect of a HIV prevention intervention and
      b) provide adequate statistical power, when used among young people from sub
      Saharan African settings with high HIV incidence rates. METHODS: Firstly, after
      having elaborated plausible scenarios based on empirical data and the
      characteristics of the BED HIV-1 Capture EIA (BED) assay, we conducted
      statistical calculations to determine the BED theoretical power and HIV incidence
      rate ratio (IRR) associated with an intervention when using BED incidence
      testing. Secondly, we simulated a cross-sectional study conducted in a population
      among whom an HIV intervention was rolled out. Simulated data were analyzed using
      a log-linear Poisson model to recalculate the IRR and its confidence interval,
      and estimate the BED practical power. Calculations were conducted with and
      without corrections for misclassifications. RESULTS: Calculations showed that BED
      incidence testing can yield a BED theoretical power of 75% or more of the power
      that can be obtained in a classical cohort study conducted over a duration equal
      to the BED window period. Statistical analyses using simulated populations showed
      that the effect of a prevention intervention can be estimated with precision
      using classical statistical analysis of BED incidence testing data, even with an
      imprecise knowledge of the characteristics of the BED assay. The BED practical
      power was lower but of the same magnitude as the BED theoretical power.
      CONCLUSIONS: BED incidence testing can be applied to reasonably small samples to
      achieve good statistical power when used among young people to estimate IRR.

PMID- 21853018
TI  - A molecular assay for sensitive detection of pathogen-specific T-cells.
AB  - Here we describe the development and validation of a highly sensitive assay of
      antigen-specific IFN-gamma production using real time quantitative PCR (qPCR) for
      two reporters--monokine-induced by IFN-gamma (MIG) and the IFN-gamma inducible
      protein-10 (IP10). We developed and validated the assay and applied it to the
      detection of CMV, HIV and Mycobacterium tuberculosis (MTB) specific responses, in
      a cohort of HIV co-infected patients. We compared the sensitivity of this assay
      to that of the ex vivo RD1 (ESAT-6 and CFP-10)-specific IFN-gamma Elispot assay.
      We observed a clear quantitative correlation between the two assays (P<0.001).
      Our assay proved to be a sensitive assay for the detection of MTB-specific T
      cells, could be performed on whole blood samples of fingerprick (50 uL) volumes,
      and was not affected by HIV-mediated immunosuppression. This assay platform is
      potentially of utility in diagnosis of infection in this and other clinical
      settings.

PMID- 21853020
TI  - HIV prevalence and incidence among sexually active females in two districts of
      South Africa to determine microbicide trial feasibility.
AB  - BACKGROUND: The suitability of populations of sexually active women in Madibeng
      (North-West Province) and Mbekweni (Western Cape), South Africa, for a Phase III
      vaginal microbicide trial was evaluated. METHODS: Sexually active women 18-35
      years not known to be HIV-positive or pregnant were tested cross-sectionally to
      determine HIV and pregnancy prevalence (798 in Madibeng and 800 in Mbekweni). Out
      of these, 299 non-pregnant, HIV-negative women were subsequently enrolled at each
      clinical research center in a 12-month cohort study with quarterly study visits.
      RESULTS: HIV prevalence was 24% in Madibeng and 22% in Mbekweni. HIV incidence
      rates based on seroconversions over 12 months were 6.0/100 person-years (PY) (95%
      CI 3.0, 9.0) in Madibeng and 4.5/100 PY (95% CI 1.8, 7.1) in Mbekweni and those
      estimated by cross-sectional BED testing were 7.1/100 PY (95% CI 2.8, 11.3) in
      Madibeng and 5.8/100 PY (95% CI 2.0, 9.6) in Mbekweni. The 12-month pregnancy
      incidence rates were 4.8/100 PY (95% CI 2.2, 7.5) in Madibeng and 7.0/100 PY (95%
      CI 3.7, 10.3) in Mbekweni; rates decreased over time in both districts. Genital
      symptoms were reported very frequently, with an incidence of 46.8/100 PY (95% CI
      38.5, 55.2) in Madibeng and 21.5/100 PY (95% CI 15.8, 27.3) in Mbekweni. Almost
      all (>99%) participants said that they would be willing to participate in a
      microbicide trial. CONCLUSION: These populations might be suitable for Phase III
      microbicide trials provided that HIV incidence rates over time remain
      sufficiently high to support endpoint-driven trials.

PMID- 21853021
TI  - Actigraph accelerometer-defined boundaries for sedentary behaviour and physical
      activity intensities in 7 year old children.
AB  - BACKGROUND: Accurate objective assessment of sedentary and physical activity
      behaviours during childhood is integral to the understanding of their relation to
      later health outcomes, as well as to documenting the frequency and distribution
      of physical activity within a population. PURPOSE: To calibrate the Actigraph
      GT1M accelerometer, using energy expenditure (EE) as the criterion measure, to
      define thresholds for sedentary behaviour and physical activity categories
      suitable for use in a large scale epidemiological study in young children.
      METHODS: Accelerometer-based assessments of physical activity (counts per minute)
      were calibrated against EE measures (kcal x kg(-1) x hr(-1)) obtained over a
      range of exercise intensities using a COSMED K4b(2) portable metabolic unit in 53
      seven-year-old children. Children performed seven activities: lying down viewing
      television, sitting upright playing a computer game, slow walking, brisk walking,
      jogging, hopscotch and basketball. Threshold count values were established to
      identify sedentary behaviour and light, moderate and vigorous physical activity
      using linear discriminant analysis (LDA) and evaluated using receiver operating
      characteristic (ROC) curve analysis. RESULTS: EE was significantly associated
      with counts for all non-sedentary activities with the exception of jogging.
      Threshold values for accelerometer counts (counts x minute(-1)) were <100 for
      sedentary behaviour and <=2240, <=3840 and >=3841 for light, moderate and
      vigorous physical activity respectively. The area under the ROC curves for
      discrimination of sedentary behaviour and vigorous activity were 0.98. Boundaries
      for light and moderate physical activity were less well defined (0.61 and 0.60
      respectively). Sensitivity and specificity were higher for sedentary (99% and
      97%) and vigorous (95% and 91%) than for light (60% and 83%) and moderate (61%
      and 76%) thresholds. CONCLUSION: The accelerometer cut points established in this
      study can be used to classify sedentary behaviour and to distinguish between
      light, moderate and vigorous physical activity in children of this age.

PMID- 21853023
TI  - The genotypic structure of a multi-host bumblebee parasite suggests a role for
      ecological niche overlap.
AB  - The genotypic structure of parasite populations is an important determinant of
      ecological and evolutionary dynamics of host-parasite interactions with
      consequences for pest management and disease control. Genotypic structure is
      especially interesting where multiple hosts co-exist and share parasites. We here
      analyze the natural genotypic distribution of Crithidia bombi, a trypanosomatid
      parasite of bumblebees (Bombus spp.), in two ecologically different habitats over
      a time period of three years. Using an algorithm to reconstruct genotypes in
      cases of multiple infections, and combining these with directly identified
      genotypes from single infections, we find a striking diversity of infection for
      both data sets, with almost all multi-locus genotypes being unique, and are
      inferring that around half of the total infections are resulting from multiple
      strains. Our analyses further suggest a mixture of clonality and sexuality in
      natural populations of this parasite species. Finally, we ask whether parasite
      genotypes are associated with host species (the phylogenetic hypothesis) or
      whether ecological factors (niche overlap in flower choice) shape the
      distribution of parasite genotypes (the ecological hypothesis). Redundancy
      analysis demonstrates that in the region with relatively high parasite
      prevalence, both host species identity and niche overlap are equally important
      factors shaping the distribution of parasite strains, whereas in the region with
      lower parasite prevalence, niche overlap more strongly contributes to the
      distribution observed. Overall, our study underlines the importance of ecological
      factors in shaping the natural dynamics of host-parasite systems.

PMID- 21853022
TI  - Multiple nuclear gene phylogenetic analysis of the evolution of dioecy and sex
      chromosomes in the genus Silene.
AB  - In the plant genus Silene, separate sexes and sex chromosomes are believed to
      have evolved twice. Silene species that are wholly or largely hermaphroditic are
      assumed to represent the ancestral state from which dioecy evolved. This
      assumption is important for choice of outgroup species for inferring the genetic
      and chromosomal changes involved in the evolution of dioecy, but is mainly based
      on data from a single locus (ITS). To establish the order of events more clearly,
      and inform outgroup choice, we therefore carried out (i) multi-nuclear-gene
      phylogenetic analyses of 14 Silene species (including 7 hermaphrodite or
      gynodioecious species), representing species from both Silene clades with
      dioecious members, plus a more distantly related outgroup, and (ii) a BayesTraits
      character analysis of the evolution of dioecy. We confirm two origins of dioecy
      within this genus in agreement with recent work on comparing sex chromosomes from
      both clades with dioecious species. We conclude that sex chromosomes evolved
      after the origin of Silene and within a clade that includes only S. latifolia and
      its closest relatives. We estimate that sex chromosomes emerged soon after the
      split with the ancestor of S. viscosa, the probable closest non-dioecious S.
      latifolia relative among the species included in our study.

PMID- 21853024
TI  - Concurrent lactation and pregnancy: pregnant domestic horse mares do not increase
      mother-offspring conflict during intensive lactation.
AB  - Lactation is the most energy demanding part of parental care in mammals, so
      parent-offspring conflict arises over milk provided by the mother. In some
      species females commonly become pregnant shortly after parturition of previous
      young. This further intensifies mother-offspring conflict due to concurrent
      pregnancy and lactation. In equids it has been well established that pregnant
      females wean their foals earlier than non-pregnant ones. Intensified mother
      offspring conflict was presumed to associate with pregnancy also during the
      period of intensive lactation, i.e., before the weaning process starts. We
      investigated the effect of pregnancy on suckling behaviour characteristics as
      indicators of mother-offspring conflict in domestic horses. Contrary to
      expectation, here we provide evidence of a decreased mother-offspring conflict
      related to pregnancy in lactating females during first two trimesters of
      pregnancy. Pregnant mares provided longer suckling bouts and did not reject or
      terminate suckling of their foals more often than non-pregnant mares. Our results
      suggest that pregnant mares cope with parallel investment into a nursed foal and
      a foetus through enhancing nursing behaviour in early stages of pregnancy before
      the initially low requirements of the foetus increase. They compensate their
      suckling foal with the perspective of its early weaning due to ongoing pregnancy.

PMID- 21853025
TI  - A bayesian method for evaluating and discovering disease loci associations.
AB  - BACKGROUND: A genome-wide association study (GWAS) typically involves examining
      representative SNPs in individuals from some population. A GWAS data set can
      concern a million SNPs and may soon concern billions. Researchers investigate the
      association of each SNP individually with a disease, and it is becoming
      increasingly commonplace to also analyze multi-SNP associations. Techniques for
      handling so many hypotheses include the Bonferroni correction and recently
      developed bayesian methods. These methods can encounter problems. Most
      importantly, they are not applicable to a complex multi-locus hypothesis which
      has several competing hypotheses rather than only a null hypothesis. A method
      that computes the posterior probability of complex hypotheses is a pressing need.
      METHODOLOGY/FINDINGS: We introduce the bayesian network posterior probability
      (BNPP) method which addresses the difficulties. The method represents the
      relationship between a disease and SNPs using a directed acyclic graph (DAG)
      model, and computes the likelihood of such models using a bayesian network
      scoring criterion. The posterior probability of a hypothesis is computed based on
      the likelihoods of all competing hypotheses. The BNPP can not only be used to
      evaluate a hypothesis that has previously been discovered or suspected, but also
      to discover new disease loci associations. The results of experiments using
      simulated and real data sets are presented. Our results concerning simulated data
      sets indicate that the BNPP exhibits both better evaluation and discovery
      performance than does a p-value based method. For the real data sets, previous
      findings in the literature are confirmed and additional findings are found.
      CONCLUSIONS/SIGNIFICANCE: We conclude that the BNPP resolves a pressing problem
      by providing a way to compute the posterior probability of complex multi-locus
      hypotheses. A researcher can use the BNPP to determine the expected utility of
      investigating a hypothesis further. Furthermore, we conclude that the BNPP is a
      promising method for discovering disease loci associations.

PMID- 21853026
TI  - Ethnic and mouse strain differences in central corneal thickness and association
      with pigmentation phenotype.
AB  - The cornea is a transparent structure that permits the refraction of light into
      the eye. Evidence from a range of studies indicates that central corneal
      thickness (CCT) is strongly genetically determined. Support for a genetic
      component comes from data showing significant variation in CCT between different
      human ethnic groups. Interestingly, these studies also appear to show that skin
      pigmentation may influence CCT. To validate these observations, we undertook the
      first analysis of CCT in an oculocutaneous albinism (OCA) and Ugandan cohort,
      populations with distinct skin pigmentation phenotypes. There was a significant
      difference in the mean CCT of the OCA, Ugandan and Australian-Caucasian cohorts
      (Ugandan: 517.3+/-37 um; Caucasian: 539.7+/-32.8 um, OCA: 563.3+/-37.2 um;
      p<0.001). A meta-analysis of 53 studies investigating the CCT of different ethnic
      groups was then performed and demonstrated that darker skin pigmentation is
      associated with a thinner CCT (p<0.001). To further verify these observations, we
      measured CCT in 13 different inbred mouse strains and found a significant
      difference between the albino and pigmented strains (p = 0.008). Specific
      mutations within the melanin synthesis pathway were then investigated in mice for
      an association with CCT. Significant differences between mutant and wild type
      strains were seen with the nonagouti (p<0.001), myosin VA (p<0.001), tyrosinase
      (p = 0.025) and tyrosinase related protein (p = 0.001) genes. These findings
      provide support for our hypothesis that pigmentation is associated with CCT and
      identifies pigment-related genes as candidates for developmental determination of
      a non-pigmented structure.

PMID- 21853027
TI  - Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic
      brain injury in a rat model of stroke.
AB  - Following the onset of an ischemic brain injury, the excitatory neurotransmitter
      glutamate is released. The excitotoxic effects of glutamate are a major
      contributor to the pathogenesis of a stroke. The aim of this study was to examine
      if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain
      injury in a rat model of stroke. We generated an adeno-associated viral (AAV)
      vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV
      GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain
      as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical
      region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion
      (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and
      TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days
      post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant
      decreases in the duration and magnitude of extracellular glutamate, measured by
      microdialysis, during the 60 minute MCAo. A significant reduction in brain
      infarction and DNA fragmentation was observed in the region of AAV-GLT1
      injection. Animals that received AAV-GLT1 showed significant improvement in
      behavioral recovery following stroke compared to the AAV-GFP group. We
      demonstrate that focal overexpression of the glutamate transporter, GLT-1,
      significantly reduces ischemia-induced glutamate overflow, decreases cell death
      and improves behavioral recovery. These data further support the role of
      glutamate in the pathogenesis of ischemic damage in brain and demonstrate that
      targeted gene delivery to decrease the ischemia-induced glutamate overflow
      reduces the cellular and behavioral deficits caused by stroke.

PMID- 21853028
TI  - Development and validation of a risk model for prediction of hazardous alcohol
      consumption in general practice attendees: the predictAL study.
AB  - BACKGROUND: Little is known about the risk of progression to hazardous alcohol
      use in people currently drinking at safe limits. We aimed to develop a prediction
      model (predictAL) for the development of hazardous drinking in safe drinkers.
      METHODS: A prospective cohort study of adult general practice attendees in six
      European countries and Chile followed up over 6 months. We recruited 10,045
      attendees between April 2003 to February 2005. 6193 European and 2462 Chilean
      attendees recorded AUDIT scores below 8 in men and 5 in women at recruitment and
      were used in modelling risk. 38 risk factors were measured to construct a risk
      model for the development of hazardous drinking using stepwise logistic
      regression. The model was corrected for over fitting and tested in an external
      population. The main outcome was hazardous drinking defined by an AUDIT score >=8
      in men and >=5 in women. RESULTS: 69.0% of attendees were recruited, of whom
      89.5% participated again after six months. The risk factors in the final
      predictAL model were sex, age, country, baseline AUDIT score, panic syndrome and
      lifetime alcohol problem. The predictAL model's average c-index across all six
      European countries was 0.839 (95% CI 0.805, 0.873). The Hedge's g effect size for
      the difference in log odds of predicted probability between safe drinkers in
      Europe who subsequently developed hazardous alcohol use and those who did not was
      1.38 (95% CI 1.25, 1.51). External validation of the algorithm in Chilean safe
      drinkers resulted in a c-index of 0.781 (95% CI 0.717, 0.846) and Hedge's g of
      0.68 (95% CI 0.57, 0.78). CONCLUSIONS: The predictAL risk model for development
      of hazardous consumption in safe drinkers compares favourably with risk
      algorithms for disorders in other medical settings and can be a useful first step
      in prevention of alcohol misuse.

PMID- 21853030
TI  - Optimal control of hepatitis C antiviral treatment programme delivery for
      prevention amongst a population of injecting drug users.
AB  - In most developed countries, HCV is primarily transmitted by injecting drug users
      (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those
      with no re-infection risk. However, few active IDUs are currently treated.
      Previous modelling studies have shown antiviral treatment for active IDUs could
      reduce HCV prevalence, and there is emerging interest in developing targeted IDU
      treatment programmes. However, the optimal timing and scale-up of treatment is
      unknown, given the real-world constraints commonly existing for health
      programmes. We explore how the optimal programme is affected by a variety of
      policy objectives, budget constraints, and prevalence settings. We develop a
      model of HCV transmission and treatment amongst active IDUs, determine the
      optimal treatment programme strategy over 10 years for two baseline chronic HCV
      prevalence scenarios (30% and 45%), a range of maximum annual budgets (L50,000
      300,000 per 1,000 IDUs), and a variety of objectives: minimising health service
      costs and health utility losses; minimising prevalence at 10 years; minimising
      health service costs and health utility losses with a final time prevalence
      target; minimising health service costs with a final time prevalence target but
      neglecting health utility losses. The largest programme allowed for a given
      budget is the programme which minimises both prevalence at 10 years, and HCV
      health utility loss and heath service costs, with higher budgets resulting in
      greater cost-effectiveness (measured by cost per QALY gained compared to no
      treatment). However, if the objective is to achieve a 20% relative prevalence
      reduction at 10 years, while minimising both health service costs and losses in
      health utility, the optimal treatment strategy is an immediate expansion of
      coverage over 5-8 years, and is less cost-effective. By contrast, if the
      objective is only to minimise costs to the health service while attaining the 20%
      prevalence reduction, the programme is deferred until the final years of the
      decade, and is the least cost-effective of the scenarios.

PMID- 21853029
TI  - Neurogenic potential of the vestibular nuclei and behavioural recovery time
      course in the adult cat are governed by the nature of the vestibular damage.
AB  - Functional and reactive neurogenesis and astrogenesis are observed in
      deafferented vestibular nuclei after unilateral vestibular nerve section in adult
      cats. The newborn cells survive up to one month and contribute actively to the
      successful recovery of posturo-locomotor functions. This study investigates
      whether the nature of vestibular deafferentation has an incidence on the
      neurogenic potential of the vestibular nuclei, and on the time course of
      behavioural recovery. Three animal models that mimic different vestibular
      pathologies were used: unilateral and permanent suppression of vestibular input
      by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL,
      the mechanical destruction of peripheral vestibular receptors), or unilateral and
      reversible blockade of vestibular nerve input using tetrodotoxin (TTX).
      Neurogenesis and astrogenesis were revealed in the vestibular nuclei using
      bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic
      protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify
      astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo
      locomotor tests (static and dynamic balance performance) were carried out to
      quantify the behavioural recovery process. Results showed that the nature of
      vestibular loss determined the cellular plastic events occurring in the
      vestibular nuclei and affected the time course of behavioural recovery.
      Interestingly, the deafferented vestibular nuclei express neurogenic potential
      after acute and total vestibular loss only (UVN), while non-structural plastic
      processes are involved when the vestibular deafferentation is less drastic (UL,
      TTX). This is the first experimental evidence that the vestibular complex in the
      brainstem can become neurogenic under specific injury. These new data are of
      interest for understanding the factors favouring the expression of functional
      neurogenesis in adult mammals in a brain repair perspective, and are of clinical
      relevance in vestibular pathology.

PMID- 21853031
TI  - DNA profiling of spermatozoa by laser capture microdissection and low volume-PCR.
AB  - Genetic profiling of sperm from complex biological mixtures such as sexual
      assault casework samples requires isolation of a pure sperm population and the
      ability to analyze low abundant samples. Current standard procedure for sperm
      isolation includes preferential lysis of epithelial contaminants followed by
      collection of intact sperm by centrifugation. While effective for samples where
      sperm are abundant, this method is less effective when samples contain few
      spermatozoa. Laser capture microdissection (LCM) is a proven method for the
      isolation of cells biological mixtures, even when found in low abundance. Here,
      we demonstrate the efficacy of LCM coupled with on-chip low volume PCR (LV-PCR)
      for the isolation and genotyping of low abundance sperm samples. Our results
      indicate that this method can obtain complete profiles (13-16 loci) from as few
      as 15 sperm cells with 80% reproducibility, whereas at least 40 sperm cells are
      required to profile 13-16 loci by standard 'in-tube' PCR. Further, LCM and LV-PCR
      of a sexual assault casework sample generated a DNA genotype that was consistent
      with that of the suspect. This method was unable, however, to analyze a casework
      sample from a gang rape case in which two or more sperm contributors were in a
      mixed population. The results indicate that LCM and LV-PCR is sensitive and
      effective for genotyping sperm from sperm/epithelial cell mixtures when
      epithelial lysis may be insufficient due to low abundance of sperm; LCM and LV
      PCR, however, failed in a casework sample when spermatozoa from multiple donors
      was present, indicating that further study is necessitated.

PMID- 21853032
TI  - Characterization of the MDSC proteome associated with metastatic murine mammary
      tumors using label-free mass spectrometry and shotgun proteomics.
AB  - Expansion of Gr-1+/CD11b+ myeloid derived suppressor cells (MDSCs) is governed by
      the presence of increasingly metastatic, malignant primary tumors. Metastasis,
      not the primary tumor, is often the cause of mortality. This study sought to
      fully characterize the MDSC proteome in response to metastatic and non-metastatic
      mammary tumors using label-free mass spectrometry shotgun proteomics in a mouse
      model with tumor cell lines, 67NR and 4T1, derived from the same tumor. 67NR
      cells form only primary mammary tumors, whereas 4T1 cells readily metastasize to
      the lungs, lymph nodes, and blood. Overall analysis identified a total of 2825
      protein groups with a 0.78% false discovery rate. Of the 2814 true
      identifications, 43 proteins were exclusive to the 67NR group, 153 were exclusive
      to the 4T1 group, and 2618 were shared. Among the shared cohort, 26 proteins were
      increased and 31 were decreased in the metastatic 4T1 cohort compared to non
      metastatic 67NR controls after filtering. MDSCs selectively express proteins
      involved in the gamma-glutamyl transferase, glutathione synthase pathways, CREB
      transcription factor signaling, and other pathways involved in platelet
      aggregation, as well as lipid and amino acid metabolism, in response to highly
      metastatic 4T1 tumors. Cell cycle regulation dominated protein pathways and
      ontological groups of the 67NR non-metastatic group. Not only does this study
      provide a starting point to identify potential biomarkers of metastasis expressed
      by MDSCs; it identifies critical pathways that are unique to non-metastatic and
      metastatic conditions. Therapeutic interventions aimed at these pathways in MDSC
      may offer a new route to control malignancy and metastasis.

PMID- 21853033
TI  - Gene network inference and biochemical assessment delineates GPCR pathways and
      CREB targets in small intestinal neuroendocrine neoplasia.
AB  - Small intestinal (SI) neuroendocrine tumors (NET) are increasing in incidence,
      however little is known about their biology. High throughput techniques such as
      inference of gene regulatory networks from microarray experiments can objectively
      define signaling machinery in this disease. Genome-wide co-expression analysis
      was used to infer gene relevance network in SI-NETs. The network was confirmed to
      be non-random, scale-free, and highly modular. Functional analysis of gene co
      expression modules revealed processes including 'Nervous system development',
      'Immune response', and 'Cell-cycle'. Importantly, gene network topology and
      differential expression analysis identified over-expression of the GPCR signaling
      regulators, the cAMP synthetase, ADCY2, and the protein kinase A, PRKAR1A. Seven
      CREB response element (CRE) transcripts associated with proliferation and
      secretion: BEX1, BICD1, CHGB, CPE, GABRB3, SCG2 and SCG3 as well as ADCY2 and
      PRKAR1A were measured in an independent SI dataset (n = 10 NETs; n = 8 normal
      preparations). All were up-regulated (p<0.035) with the exception of SCG3 which
      was not differently expressed. Forskolin (a direct cAMP activator, 10(-5) M)
      significantly stimulated transcription of pCREB and 3/7 CREB targets,
      isoproterenol (a selective beta-adrenergic receptor agonist and cAMP activator,
      10(-5) M) stimulated pCREB and 4/7 targets while BIM-53061 (a dopamine D(2) and
      Serotonin [5-HT(2)] receptor agonist, 10(-6) M) stimulated 100% of targets as
      well as pCREB; CRE transcription correlated with the levels of cAMP accumulation
      and PKA activity; BIM-53061 stimulated the highest levels of cAMP and PKA (2.8
      fold and 2.5-fold vs. 1.8-2-fold for isoproterenol and forskolin). Gene network
      inference and graph topology analysis in SI NETs suggests that SI NETs express
      neural GPCRs that activate different CRE targets associated with proliferation
      and secretion. In vitro studies, in a model NET cell system, confirmed that
      transcriptional effects are signaled through the cAMP/PKA/pCREB signaling pathway
      and that a SI NET cell line was most sensitive to a D(2) and 5-HT(2) receptor
      agonist BIM-53061.

PMID- 21853034
TI  - Global diversity of aloricate Oligotrichea (Protista, Ciliophora, Spirotricha) in
      marine and brackish sea water.
AB  - Oligotrichids and choreotrichids are ciliate taxa contributing to the multi-step
      microbial food web and episodically dominating the marine microzooplankton. The
      global diversity and distribution of aloricate Oligotrichea are unknown. Here,
      the geographic ranges of the 141 accepted species and their synonyms in marine
      and brackish sea water are analyzed, using hundreds of taxonomical and ecological
      studies; the quality of the records is simultaneously evaluated. The aloricate
      Oligotrichea match the moderate endemicity model, i.e., the majority (94) of
      morphospecies has a wide, occasionally cosmopolitan distribution, while 47
      morphospecies show biogeographic patterns: they are restricted to single
      geographic regions and probably include 12 endemic morphospecies. These endemics
      are found in the Antarctic, North Pacific, and Black Sea, whereas the "flagship"
      species Strombidinopsis cercionis is confined to the Caribbean Sea. Concerning
      genera, again several geographic patterns are recognizable. The species richness
      is distinctly lower in the southern hemisphere than in the northern, ranging from
      nine morphospecies in the South Pacific to 95 in the North Atlantic; however,
      this pattern is probably caused by undersampling. Since the loss of species might
      affect higher trophical levels substantially, the aloricate Oligotrichea should
      not any longer be ignored in conservation issues. The ecophysiological diversity
      is considerably larger than the morphological, and even tops the richness of
      SSrRNA and ITS haplotypes, indicating that probably more than 83-89% of the
      diversity in aloricate Oligotrichea are unknown. The huge challenge to discover
      all these species can only be managed by combining the expertises of
      morphological taxonomists, molecular biologists, ecologists, and physiologists.

PMID- 21853035
TI  - Evidence for air movement signals in the agonistic behaviour of a nocturnal
      arachnid (order Amblypygi).
AB  - Many arthropods possess filiform hair sensilla (termed trichobothria in
      arachnids), which are extremely sensitive detectors of medium particle
      displacement. Electrophysiological evidence in some taxa suggests that these
      sensilla can detect air particle displacements resulting from intraspecific
      communication signals. However, it has not yet been shown for any species that
      the air particle displacements detected by the filiform hairs are themselves
      perceived as a 'signal' (i.e. that individuals make behavioural decisions based
      upon the responses of these organs to the displays of conspecifics). We
      investigate the agonistic behaviour of the whip spider Phrynus marginemaculatus
      and the role of its trichobothria in receiving agonistic signals. Whip spiders
      have extremely elongated 'antenniform' first legs, which they vibrate close to
      their opponents during agonistic interactions, inducing air movements that excite
      their opponents' trichobothria. We find that ablation of the trichobothria causes
      significant increases in: (I) contest duration, and (II) the probability of
      contest escalation past aggressive displays to physical fighting. Therefore, in
      the absence of air movement-sensitive sensilla, contest assessment is impaired.
      This suggests that whip spiders exploit true air movement signals during
      agonistic interactions, and that these are received by the trichobothria.
      Furthermore, these results indicate that, in whip spiders, such signals help
      mitigate the cost of agonistic interaction.

PMID- 21853036
TI  - Serotonin-mediated tuning of human helper T cell responsiveness to the chemokine
      CXCL12.
AB  - In addition to its role as neurotransmitter, serotonin (5-HT) is an important
      modulator of inflammation and immunity. Here, we report novel findings suggesting
      a 5-HT involvement in T cell migration. In particular, we show that 5-HT tunes
      the responsiveness of human T lymphocytes to the broadly expressed chemokine
      CXCL12 in transwell migration assays. By real-time PCR, western blot analysis and
      electrophysiological patch clamp experiments, we demonstrate that the type 3 5-HT
      receptor (5-HT(3)) is functionally expressed in human primary T cells. In
      addition, specific 5-HT(3) receptor agonists selectively decrease T cell
      migration towards gradients of CXCL12 but not of inflammatory chemokines, such as
      CCL2 and CCL5. In transmigration experiments, 5-HT(3) receptor stimulation
      reverts the inhibitory effect of endothelial-bound CXCL12 on T cell migration.
      Our data suggest that the reduced T cell responsiveness to CXCL12 induced by 5-HT
      may occur to facilitate T cell extravasation and migration into inflamed tissues.

PMID- 21853037
TI  - Serum methionine metabolites are risk factors for metastatic prostate cancer
      progression.
AB  - BACKGROUND: Clinical decision for primary treatment for prostate cancer is
      dictated by variables with insufficient specificity. Early detection of prostate
      cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics
      and adjuvant options prior to frank biochemical recurrence. This study compared
      markers in serum and urine of patients with rapidly recurrent prostate cancer to
      recurrence-free patients after radical prostatectomy. Based on previous
      identification of urinary sarcosine as a metastatic marker, we tested whether
      methionine metabolites in urine and serum could serve as pre-surgical markers for
      aggressive disease. METHODOLOGY/PRINCIPAL FINDINGS: Urine and serum samples (n =
      54 and 58, respectively), collected at the time of prostatectomy were divided
      into subjects who developed biochemical recurrence within 2 years and those who
      remained recurrence-free after 5 years. Multiple methionine metabolites were
      measured in urine and serum by GC-MS. The role of serum metabolites and clinical
      variables (biopsy Gleason grade, clinical stage, serum prostate specific antigen
      [PSA]) on biochemical recurrence prediction were evaluated. Urinary sarcosine and
      cysteine levels were significantly higher (p = 0.03 and p = 0.007 respectively)
      in the recurrent group. However, in serum, concentrations of homocysteine (p =
      0.003), cystathionine (p = 0.007) and cysteine (p<0.001) were more abundant in
      the recurrent population. The inclusion of serum cysteine to a model with PSA and
      biopsy Gleason grade improved prediction over the clinical variables alone
      (p<0.001). CONCLUSIONS: Higher serum homocysteine, cystathionine, and cysteine
      concentrations independently predicted risk of early biochemical recurrence and
      aggressiveness of disease in a nested case control study. The methionine
      metabolites further supplemented known clinical variables to provide superior
      sensitivity and specificity in multivariable prediction models for rapid
      biochemical recurrence following prostatectomy.

PMID- 21853038
TI  - Multimodal pyrethroid resistance in malaria vectors, Anopheles gambiae s.s.,
      Anopheles arabiensis, and Anopheles funestus s.s. in western Kenya.
AB  - Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus s.s. are the
      most important species for malaria transmission. Pyrethroid resistance of these
      vector mosquitoes is one of the main obstacles against effective vector control.
      The objective of the present study was to monitor the pyrethroid susceptibility
      in the 3 major malaria vectors in a highly malaria endemic area in western Kenya
      and to elucidate the mechanisms of pyrethroid resistance in these species. Gembe
      East and West, Mbita Division, and 4 main western islands in the Suba district of
      the Nyanza province in western Kenya were used as the study area. Larval and
      adult collection and bioassay were conducted, as well as the detection of point
      mutation in the voltage-gated sodium channel (1014L) by using direct DNA
      sequencing. A high level of pyrethroid resistance caused by the high frequency of
      point mutations (L1014S) was detected in An. gambiae s.s. In contrast, P450
      related pyrethroid resistance seemed to be widespread in both An. arabiensis and
      An. funestus s.s. Not a single L1014S mutation was detected in these 2 species. A
      lack of cross-resistance between DDT and permethrin was also found in An.
      arabiensis and An. funestus s.s., while An. gambiae s.s. was resistant to both
      insecticides. It is noteworthy that the above species in the same area are found
      to be resistant to pyrethroids by their unique resistance mechanisms.
      Furthermore, it is interesting that 2 different resistance mechanisms have
      developed in the 2 sibling species in the same area individually. The cross
      resistance between permethrin and DDT in An. gambiae s.s. may be attributed to
      the high frequency of kdr mutation, which might be selected by the frequent
      exposure to ITNs. Similarly, the metabolic pyrethroid resistance in An.
      arabiensis and An. funestus s.s. is thought to develop without strong selection
      by DDT.

PMID- 21853039
TI  - Predicting final extent of ischemic infarction using artificial neural network
      analysis of multi-parametric MRI in patients with stroke.
AB  - In hemispheric ischemic stroke, the final size of the ischemic lesion is the most
      important correlate of clinical functional outcome. Using a set of acute-phase MR
      images (Diffusion-weighted--DWI, T(1)-weighted--T1WI, T(2)-weighted--T2WI, and
      proton density weighted--PDWI) for inputs, and the chronic T2WI at 3 months as an
      outcome measure, an Artificial Neural Network (ANN) was trained to predict the 3
      month outcome in the form of a voxel-by-voxel forecast of the chronic T2WI. The
      ANN was trained and tested using 12 subjects (with 83 slices and 140218 voxels)
      using a leave-one-out cross-validation method with calculation of the Area Under
      the Receiver Operator Characteristic Curve (AUROC) for training, testing and
      optimization of the ANN. After training and optimization, the ANN produced maps
      of predicted outcome that were well correlated (r = 0.80, p<0.0001) with the T2WI
      at 3 months for all 12 patients. This result implies that the trained ANN can
      provide an estimate of 3-month ischemic lesion on T2WI in a stable and accurate
      manner (AUROC = 0.89).

PMID- 21853040
TI  - The microbial detection array combined with random Phi29-amplification used as a
      diagnostic tool for virus detection in clinical samples.
AB  - A common technique used for sensitive and specific diagnostic virus detection in
      clinical samples is PCR that can identify one or several viruses in one assay.
      However, a diagnostic microarray containing probes for all human pathogens could
      replace hundreds of individual PCR-reactions and remove the need for a clear
      clinical hypothesis regarding a suspected pathogen. We have established such a
      diagnostic platform for random amplification and subsequent microarray
      identification of viral pathogens in clinical samples. We show that Phi29
      polymerase-amplification of a diverse set of clinical samples generates enough
      viral material for successful identification by the Microbial Detection Array,
      demonstrating the potential of the microarray technique for broad-spectrum
      pathogen detection. We conclude that this method detects both DNA and RNA virus,
      present in the same sample, as well as differentiates between different virus
      subtypes. We propose this assay for diagnostic analysis of viruses in clinical
      samples.

PMID- 21853041
TI  - Hierarchical differentiation of myeloid progenitors is encoded in the
      transcription factor network.
AB  - Hematopoiesis is an ideal model system for stem cell biology with advanced
      experimental access. A systems view on the interactions of core transcription
      factors is important for understanding differentiation mechanisms and dynamics.
      In this manuscript, we construct a Boolean network to model myeloid
      differentiation, specifically from common myeloid progenitors to megakaryocytes,
      erythrocytes, granulocytes and monocytes. By interpreting the hematopoietic
      literature and translating experimental evidence into Boolean rules, we implement
      binary dynamics on the resulting 11-factor regulatory network. Our network
      contains interesting functional modules and a concatenation of mutual
      antagonistic pairs. The state space of our model is a hierarchical, acyclic
      graph, typifying the principles of myeloid differentiation. We observe excellent
      agreement between the steady states of our model and microarray expression
      profiles of two different studies. Moreover, perturbations of the network
      topology correctly reproduce reported knockout phenotypes in silico. We predict
      previously uncharacterized regulatory interactions and alterations of the
      differentiation process, and line out reprogramming strategies.

PMID- 21853042
TI  - Characterization of the PRMT gene family in rice reveals conservation of arginine
      methylation.
AB  - Post-translational methylation of arginine residues profoundly affects the
      structure and functions of protein and, hence, implicated in a myriad of
      essential cellular processes such as signal transduction, mRNA splicing and
      transcriptional regulation. Protein arginine methyltransferases (PRMTs), the
      enzymes catalyzing arginine methylation have been extensively studied in animals,
      yeast and, to some extent, in model plant Arabidopsis thaliana. Eight genes
      coding for the PRMTs were identified in Oryza sativa, previously. Here, we report
      that these genes show distinct expression patterns in various parts of the plant.
      In vivo targeting experiment demonstrated that GFP-tagged OsPRMT1, OsPRMT5 and
      OsPRMT10 were localized to both the cytoplasm and nucleus, whereas OsPRMT6a and
      OsPRMT6b were predominantly localized to the nucleus. OsPRMT1, OsPRMT4, OsPRMT5,
      OsPRMT6a, OsPRMT6b and OsPRMT10 exhibited in vitro arginine methyltransferase
      activity against myelin basic protein, glycine-arginine-rich domain of
      fibrillarin and calf thymus core histones. Furthermore, they depicted
      specificities for the arginine residues in histones H3 and H4 and were classified
      into type I and Type II PRMTs, based on the formation of type of dimethylarginine
      in the substrate proteins. The two homologs of OsPRMT6 showed direct interaction
      in vitro and further titrating different amounts of these proteins in the
      methyltransferase assay revealed that OsPRMT6a inhibits the methyltransferase
      activity of OsPRMT6b, probably, by the formation of heterodimer. The
      identification and characterization of PRMTs in rice suggests the conservation of
      arginine methylation in monocots and hold promise for gaining further insight
      into regulation of plant development.

PMID- 21853043
TI  - A subadult specimen of Rubeosaurus ovatus (Dinosauria: Ceratopsidae), with
      observations on other ceratopsids from the two medicine formation.
AB  - BACKGROUND: Centrosaurine ceratopsids are well known from the middle Campanian
      Upper Two Medicine Formation of Montana. Four taxa have been named:
      Brachyceratops montanensis, Rubeosaurus ovatus, Einiosaurus procurvicornis, and
      Achelousaurus horneri. Rubeosaurus has been historically the most enigmatic of
      these taxa; only two specimens, the holotype caudal parietal bar and a referred
      incomplete skull, have been assigned to Rubeosaurus. METHODOLOGY/PRINCIPAL
      FINDINGS: A revised interpretation of the parietal processes of USNM 14765, the
      partial skeleton of a subadult centrosaurine formerly referred to Brachyceratops,
      indicates that it shares a P5 spike with the holotype of Rubeosaurus ovatus and
      should therefore be referred to that taxon. Brachyceratops is considered a nomen
      dubium. CONCLUSIONS/SIGNIFICANCE: USNM 14765 provides additional anatomical
      information for Rubeosaurus ovatus. These new data are incorporated into a recent
      phylogenetic analysis of centrosaurine relationships; Rubeosaurus appears as the
      sister taxon of a clade composed of Einiosaurus, Achelousaurus, and
      Pachyrhinosaurus.

PMID- 21853044
TI  - Alternative spliced CD1d transcripts in human bronchial epithelial cells.
AB  - CD1d is a MHC I like molecule which presents glycolipid to natural killer T (NKT)
      cells, a group of cells with diverse but critical immune regulatory functions in
      the immune system. These cells are required for optimal defence against
      bacterial, viral, protozoan, and fungal infections, and control of immune
      pathology and autoimmune diseases. CD1d is expressed on antigen presenting cells
      but also found on some non-haematopoietic cells. However, it has not been
      observed on bronchial epithelium, a site of active host defence in the lungs.
      Here, we identify for the first time, CD1D mRNA variants and CD1d protein
      expression on human bronchial epithelial cells, describe six alternatively
      spliced transcripts of this gene in these cells; and show that these variants are
      specific to epithelial cells. These findings provide the basis for investigations
      into a role for CD1d in lung mucosal immunity.

PMID- 21853046
TI  - Fear of fishers: human predation explains behavioral changes in coral reef
      fishes.
AB  - Prey flight decisions in response to predation risk are increasingly being
      considered in conservation and management decisions in the terrestrial realm, but
      are rarely considered in marine systems. This field-based study investigated how
      the behavioral response of coral reef fish families varied along a gradient of
      subsistence fishing pressure in Papua New Guinea. Specifically, we examined how
      fishing pressure was related to pre-flight behavior and flight initiation
      distance (FID), and whether FID was influenced by body size (centimeters total
      length), group size (including both con- and hetero-specific individuals), or
      life-history phase. Fishing pressure was positively associated with higher FID,
      but only in families that were primarily targeted by spear guns. Among these
      families, there were variable responses in FID; some families showed increased
      FID monotonically with fishing pressure, while others showed increased FID only
      at the highest levels of fishing pressure. Body size was more significant in
      varying FID at higher levels of fishing pressure. Although family-level
      differences in pre-flight behavior were reported, such behavior showed low
      concordance with fishing pressure. FID shows promise as a tool by which
      compliance and effectiveness of management of reef fisheries can be assessed.

PMID- 21853045
TI  - Myosin VI regulates actin structure specialization through conserved cargo
      binding domain sites.
AB  - Actin structures are often stable, remaining unchanged in organization for the
      lifetime of a differentiated cell. Little is known about stable actin structure
      formation, organization, or maintenance. During Drosophila spermatid
      individualization, long-lived actin cones mediate cellular remodeling. Myosin VI
      is necessary for building the dense meshwork at the cones' fronts. We test
      several ideas for myosin VI's mechanism of action using domain deletions or site
      specific mutations of myosin VI. The head (motor) and globular tail (cargo
      binding) domains were both needed for localization at the cone front and dense
      meshwork formation. Several conserved partner-binding sites in the globular tail
      previously identified in vertebrate myosin VI were critical for function in
      cones. Localization and promotion of proper actin organization were separable
      properties of myosin VI. A vertebrate myosin VI was able to localize and
      function, indicating that functional properties are conserved. Our data eliminate
      several models for myosin VI's mechanism of action and suggest its role is
      controlling organization and action of actin assembly regulators through
      interactions at conserved sites. The Drosophila orthologues of interaction
      partners previously identified for vertebrate myosin VI are likely not required,
      indicating novel partners mediate this effect. These data demonstrate that
      generating an organized and functional actin structure in this cell requires
      multiple activities coordinated by myosin VI.

PMID- 21853047
TI  - Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis,
      neuromyelitis optica, and multiple sclerosis.
AB  - BACKGROUND: Brain stem lesions are common in patients with acute disseminated
      encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis
      (MS). OBJECTIVES: To investigate comparative brain stem lesions on magnetic
      resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. METHODS:
      Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who
      had brain stem lesions on MRI were enrolled. Morphological features of brain stem
      lesions among these diseases were assessed. RESULTS: Patients with ADEM had a
      higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%,
      P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower
      frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001)
      and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher
      frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs.
      35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the
      brain stem, the majority (82.4%) of patients with ADEM showed lesions on the
      ventral part; the brain stem lesions in patients with NMO were typically located
      in the dorsal part (91.3%); and lesions in patients with MS were found in both
      the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM
      (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with
      MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM
      were usually bilateral and symmetrical (82.4%), while lesions in patients with
      NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. CONCLUSIONS: Brain
      stem lesions showed various morphological features among adult patients with
      ADEM, NMO, and MS. The different lesion locations may be helpful in
      distinguishing these diseases.

PMID- 21853048
TI  - Calculation of the relative chemical stabilities of proteins as a function of
      temperature and redox chemistry in a hot spring.
AB  - Uncovering the chemical and physical links between natural environments and
      microbial communities is becoming increasingly amenable owing to geochemical
      observations and metagenomic sequencing. At the hot spring known as Bison Pool in
      Yellowstone National Park, the cooling of the water in the outflow channel is
      associated with an increase in oxidation potential estimated from multiple field
      based measurements. Representative groups of proteins whose sequences were
      derived from metagenomic data also exhibit an increase in average oxidation state
      of carbon in the protein molecules with distance from the hot-spring source. The
      energetic requirements of reactions to form selected proteins used in the model
      were computed using amino-acid group additivity for the standard molal
      thermodynamic properties of the proteins, and the relative chemical stabilities
      of the proteins were investigated by varying temperature, pH and oxidation state,
      expressed as activity of dissolved hydrogen. The relative stabilities of the
      proteins were found to track the locations of the sampling sites when the
      calculations included a function for hydrogen activity that increases with
      temperature and is higher, or more reducing, than values consistent with
      measurements of dissolved oxygen, sulfide and oxidation-reduction potential in
      the field. These findings imply that spatial patterns in the amino acid
      compositions of proteins can be linked, through energetics of overall chemical
      reactions representing the formation of the proteins, to the environmental
      conditions at this hot spring, even if microbial cells maintain considerably
      different internal conditions. Further applications of the thermodynamic
      calculations are possible for other natural microbial ecosystems.

PMID- 21853049
TI  - Treatment of inflammatory bowel disease associated E. coli with ciprofloxacin and
      E. coli Nissle in the streptomycin-treated mouse intestine.
AB  - BACKGROUND: E. coli belonging to the phylogenetic group B2 are linked to
      Inflammatory Bowel Disease (IBD). Studies have shown that antimicrobials have
      some effect in the treatment of IBD, and it has been demonstrated that E. coli
      Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA)
      therapy in ulcerative colitis. The objective of this study was to test if
      ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the
      streptomycin-treated mouse intestine. RESULTS: After successful colonization with
      the IBD associated E. coli strains in mice the introduction of E. coli Nissle did
      not result in eradication of either IBD associated strains or an E. coli from a
      healthy control, instead, co-colonization at high levels were obtained. Treatment
      of mice, precolonized with IBD associated E. coli, with ciprofloxacin for three
      days alone apparently resulted in effective eradication of tested E. coli.
      However, treatment of precolonized mice with a combination of ciprofloxacin for 3
      days followed by E. coli Nissle surprisingly allowed one IBD associated E. coli
      to re-colonize the mouse intestine, but at a level 3 logs under E. coli Nissle. A
      prolonged treatment with ciprofloxacin for 7 days did not change this outcome.
      CONCLUSIONS: In the mouse model E. coli Nissle can not be used alone to eradicate
      IBD associated E. coli; rather, 3 days of ciprofloxacin are apparently efficient
      in eradicating these strains, but surprisingly, after ciprofloxacin treatment (3
      or 7 days), the introduction of E. coli Nissle may support re-colonization with
      IBD associated E. coli.

PMID- 21853050
TI  - Elevated hemostasis markers after pneumonia increases one-year risk of all-cause
      and cardiovascular deaths.
AB  - BACKGROUND: Acceleration of chronic diseases, particularly cardiovascular
      disease, may increase long-term mortality after community-acquired pneumonia
      (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic
      state that occurs during an acute infection may increase risk of subsequent
      atherothrombosis in patients with pre-existing cardiovascular disease and
      increase subsequent risk of death. We hypothesized that circulating hemostasis
      markers activated during CAP persist at hospital discharge, when patients appear
      to have recovered clinically, and are associated with higher mortality,
      particularly due to cardiovascular causes. METHODS: In a cohort of survivors of
      CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin
      complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1
      at hospital discharge, and determined 1-year all-cause and cardiovascular
      mortality. RESULTS: Of 893 subjects, most did not have severe pneumonia (70.6%
      never developed severe sepsis) and only 13.4% required intensive care unit
      admission. At discharge, 88.4% of subjects had normal vital signs and appeared to
      have clinically recovered. D-dimer and TAT levels were elevated at discharge in
      78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe
      sepsis. Higher D-dimer and TAT levels were associated with higher risk of all
      cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04,
      p = 0.001 after adjusting for demographics and comorbid illnesses) and
      cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses).
      CONCLUSIONS: Elevations of TAT and D-dimer levels are common at hospital
      discharge in patients who appeared to have recovered clinically from pneumonia
      and are associated with higher risk of subsequent deaths, particularly due to
      cardiovascular disease.

PMID- 21853052
TI  - Single molecule analysis of c-myb alternative splicing reveals novel classifiers
      for precursor B-ALL.
AB  - The c-Myb transcription factor, a key regulator of proliferation and
      differentiation in hematopoietic and other cell types, has an N-terminal DNA
      binding domain and a large C-terminal domain responsible for transcriptional
      activation, negative regulation and determining target gene specificity.
      Overexpression and rearrangement of the c-myb gene (MYB) has been reported in
      some patients with leukemias and other types of cancers, implicating activated
      alleles of c-myb in the development of human tumors. Alternative RNA splicing can
      produce variants of c-myb with qualitatively distinct transcriptional activities
      that may be involved in transformation and leukemogenesis. Here, by performing a
      detailed, single molecule assay we found that c-myb alternative RNA splicing was
      elevated and much more complex in leukemia samples than in cell lines or CD34+
      hematopoietic progenitor cells from normal donors. The results revealed that
      leukemia samples express more than 60 different c-myb splice variants, most of
      which have multiple alternative splicing events and were not detectable by
      conventional microarray or PCR approaches. For example, the single molecule assay
      detected 21 and 22 splice variants containing the 9B and 9S exons, respectively,
      most of which encoded unexpected variant forms of c-Myb protein. Furthermore, the
      detailed analysis identified some splice variants whose expression correlated
      with poor survival in a small cohort of precursor B-ALL samples. Our findings
      indicate that single molecule assays can reveal complexities in c-myb alternative
      splicing that have potential as novel biomarkers and could help explain the role
      of c-Myb variants in the development of human leukemia.

PMID- 21853053
TI  - Cost-effectiveness of opportunistic screening and minimal contact psychotherapy
      to prevent depression in primary care patients.
AB  - BACKGROUND: Depression causes a large burden of disease worldwide. Effective
      prevention has the potential to reduce that burden considerably. This study aimed
      to investigate the cost-effectiveness of minimal contact psychotherapy, based on
      Lewinsohn's 'Coping with depression' course, targeted at opportunistically
      screened individuals with sub-threshold depression. METHODS AND RESULTS: Using a
      Markov model, future health effects and costs of an intervention scenario and a
      current practice scenario were estimated. The time horizon was five years.
      Incremental cost-effectiveness ratios were expressed in euro per Disability
      Adjusted Life Year (DALY) averted. Probabilistic sensitivity analysis was
      employed to study the effect of uncertainty in the model parameters. From the
      health care perspective the incremental cost-effectiveness ratio was ? 1,400 per
      DALY, and from the societal perspective the intervention was cost-saving.
      Although the estimated incremental costs and effects were surrounded with large
      uncertainty, given a willingness to pay of ? 20,000 per DALY, the probability
      that the intervention is cost-effective was around 80%. CONCLUSION: This
      modelling study showed that opportunistic screening in primary care for sub
      threshold depression in combination with minimal contact psychotherapy may be
      cost-effective in the prevention of major depression.

PMID- 21853054
TI  - RD antigen based nanovaccine imparts long term protection by inducing memory
      response against experimental murine tuberculosis.
AB  - BACKGROUND: The absence of certain genomic loci that are present in most of the
      virulent strains of Mycobacterium tuberculosis as well as lack of lasting memory
      responses are some of the major causes attributed to the non effectiveness of
      Bacille Calmette-Gue'rin (BCG) vaccine. Immunization schedules addressing these
      issues can offer better strategy for protection against tuberculosis. METHODS:
      The immunological responses evoked upon administration of archaeosome based
      antigen delivery system comprising T cell antigen, Rv3619c (an ESAT-6 family
      protein), has been assessed against experimental murine tuberculosis in BALB/c
      mice. RESULTS: Archaeosome based subunit vaccine has been found to elicit type-1
      cytokines in the immunized mice. Besides effective T cell memory response, the
      Rv3619c based vaccine was able to reduce mycobacterial burden in the animals
      challenged with Mycobacterium tuberculosis infection. CONCLUSION: The data of the
      present study suggest that archaeosome encapsulated RD gene products offer
      substantial protection against M. tuberculosis infection.

PMID- 21853055
TI  - Diversity of the Monstrilloida (Crustacea: Copepoda).
AB  - Monstrilloid copepods are protelean parasites of different groups of marine
      benthic invertebrates. Only their first naupliar, preadult, and adult phases are
      planktonic. Monstrilloids are currently represented by more than 115 nominal
      species contained in four genera. Its taxonomic knowledge has been hampered by
      nomenclatural and descriptive problems derived from their peculiar ontogeny and
      poor definitions of taxa. One of the most important difficulties is that of
      matching males to females. The only reliable methods to link the sexes of a
      species are the confirmation of particular apomorphies shared by both sexes,
      finding both sexes in the same host or as a pre-copulatory male-female pair in
      the plankton, or by the use of molecular markers. A general overview of the
      morphology of the group and its life cycle is provided herein. Recently, upgraded
      descriptive standards have been established and the relevance of redescribing
      taxa based on type and museum specimens has been demonstrated. The rate of
      species description per decade has had several peaks between 1840 and 2010: (1971
      1980, 1991-2000, 2001-2010), each related to the activity of a few researchers.
      An analysis of the world distribution of published records of the Monstrilloida
      revealed that the Northeast Atlantic is the best studied region (45% of all
      records), followed by the Northwestern Atlantic (17%); the least surveyed areas
      include regions of the southern hemisphere (less than 3%). The Northeast Atlantic
      region harbors the highest number of known species (32 nominal species), followed
      by the Caribbean Sea/Gulf of Mexico (24), the Mediterranean/Black Sea (19),
      Indonesia-Malaysia-Philippines region (17), Japanese waters (17), and the Brazil
      Argentina area (16). Other than these generalized patterns, little can be
      concluded concerning the biogeography of the group. Many species records are
      doubtful or improbable, and purportedly cosmopolitan nominal species are being
      revealed as species complexes yet to be studied.

PMID- 21853051
TI  - Serum cholesterol and the progression of Parkinson's disease: results from
      DATATOP.
AB  - BACKGROUND: Recent studies have suggested that higher serum cholesterol may be
      associated with lower occurrence of Parkinson's disease (PD). This study is to
      test the hypothesis that higher serum cholesterol correlates with slower PD
      progression. METHODS: Baseline non-fasting serum total cholesterol was measured
      in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the
      Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial.
      Participants were followed for up to two years, with clinical disability
      requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs) and 95%
      confidence intervals (CI) were determined for increasing serum cholesterol
      concentration (in quintiles) for clinical disability requiring levodopa therapy,
      after adjusting for confounders. At baseline, only nine subjects reported use of
      cholesterol-lowering agents (two with statins). RESULTS: The overall mean
      cholesterol level was 216 mg/dL (range 100-355). The HR of progressing to the
      primary endpoint decreased with increasing serum cholesterol concentrations.
      Compared to the lowest quintile, the HRs (95%CI), for each higher quintile (in
      ascending order) are 0.83 (0.59-1.16); 0.86 (0.61-1.20); 0.84 (0.60-1.18); and
      0.75 (0.52-1.09). The HR for one standard deviation (SD) increase = 0.90 [(0.80
      1.01), p for trend = 0.09]. This trend was found in males (HR per SD = 0.88
      [(0.77-1.00), p for trend = 0.05], but not in females [HR = 1.03 (0.81-1.32)].
      CONCLUSIONS: This secondary analysis of the DATATOP trial provides preliminary
      evidence that higher total serum cholesterol concentrations may be associated
      with a modest slower clinical progression of PD, and this preliminary finding
      needs confirmation from larger prospective studies.

PMID- 21853056
TI  - Latent membrane protein 1 is dispensable for Epstein-Barr virus replication in
      human embryonic kidney 293 cells.
AB  - Epstein Barr Virus (EBV) replicates in oral epithelial cells and gains entry to B
      lymphocytes. In B-lymphocytes, EBV expresses a restricted subset of genes, the
      Latency III program, which converts B-lymphocytes to proliferating lymphoblasts.
      Latent Membrane Protein 1 (LMP1) and the other Latency III associated proteins
      are also expressed during virus replication. LMP1 is essential for virus
      replication and egress from Akata Burkitt Lymphoma cells, but a role in
      epithelial cell replication has not been established. Therefore, we have
      investigated whether LMP1 enhances EBV replication and egress from HEK293 cells,
      a model epithelial cell line used for EBV recombinant molecular genetics. We
      compared wild type (wt) and LMP1-deleted (LMP1Delta) EBV bacterial artificial
      chromosome (BAC) based virus replication and egress from HEK293. Following EBV
      immediate early Zta protein induction of EBV replication in HEK293 cells, similar
      levels of EBV proteins were expressed in wt- and LMP1Delta-infected HEK293 cells.
      LMP1 deletion did not impair EBV replication associated DNA replication, DNA
      encapsidation, or mature virus release. Indeed, virus from LMP1Delta-infected
      HEK293 cells was as infectious as EBV from wt EBV infected HEK cells. Trans
      complementation with LMP1 reduced Rta expression and subsequent virus production.
      These data indicate that LMP1 is not required for EBV replication and egress from
      HEK293 cells.

PMID- 21853057
TI  - Mitotic catastrophe occurs in the absence of apoptosis in p53-null cells with a
      defective G1 checkpoint.
AB  - Cell death occurring during mitosis, or mitotic catastrophe, often takes place in
      conjunction with apoptosis, but the conditions in which mitotic catastrophe may
      exhibit features of programmed cell death are still unclear. In the work
      presented here, we studied mitotic cell death by making use of a UV-inactivated
      parvovirus (adeno-associated virus; AAV) that has been shown to induce a DNA
      damage response and subsequent death of p53-defective cells in mitosis, without
      affecting the integrity of the host genome. Osteosarcoma cells (U2OSp53DD) that
      are deficient in p53 and lack the G1 cell cycle checkpoint respond to AAV
      infection through a transient G2 arrest. We found that the infected U2OSp53DD
      cells died through mitotic catastrophe with no signs of chromosome condensation
      or DNA fragmentation. Moreover, cell death was independent of caspases, apoptosis
      inducing factor (AIF), autophagy and necroptosis. These findings were confirmed
      by time-lapse microscopy of cellular morphology following AAV infection. The
      assays used readily revealed apoptosis in other cell types when it was indeed
      occurring. Taken together the results indicate that in the absence of the G1
      checkpoint, mitotic catastrophe occurs in these p53-null cells predominantly as a
      result of mechanical disruption induced by centrosome overduplication, and not as
      a consequence of a suicide signal.

PMID- 21853058
TI  - The impact of utilizing different optical coherence tomography devices for
      clinical purposes and in multiple sclerosis trials.
AB  - Optical coherence tomography (OCT) derived retinal measures, particularly peri
      papillary retinal nerve fiber layer (RNFL) thickness, have been proposed as
      outcome measures in remyelinating and neuroprotective trials in multiple
      sclerosis (MS). With increasing utilization of multiple centers to improve power,
      elucidation of the impact of different OCT technologies is crucial to the design
      and interpretation of such studies. In this study, we assessed relation and
      agreement between RNFL thickness and total macular volume (in MS and healthy
      controls) derived from three commonly used OCT devices: Stratus time-domain OCT,
      and Cirrus HD-OCT and Spectralis, two spectral-domain (SD) OCT devices. OCT was
      performed on both Cirrus HD-OCT and Stratus in 229 participants and on both
      Cirrus HD-OCT and Spectralis in a separate cohort of 102 participants. Pearson
      correlation and Bland-Altman analyses were used to assess correlation and
      agreement between devices. All OCT retinal measures correlated highly between
      devices. The mean RNFL thickness was 7.4 um lower on Cirrus HD-OCT than Stratus,
      indicating overall poor agreement for this measurement between these machines.
      Further, the limits of agreement (LOA) between Cirrus HD-OCT and Stratus were
      wide (-4.1 to 18.9 um), indicating poor agreement at an individual subject level.
      The mean RNFL thickness was 1.94 um (LOA: -5.74 to 9.62 um) higher on Spectralis
      compared to Cirrus HD-OCT, indicating excellent agreement for this measurement
      across this cohort. Although these data indicate that these three devices agree
      poorly at an individual subject level (evidenced by wide LOA in both study
      cohorts) precluding their co-utilization in everyday practice, the small
      difference for mean measurements between Cirrus HD-OCT and Spectralis indicate
      pooled results from these two SD-devices could be used as outcome measures in
      clinical trials, provided patients are scanned on the same machine throughout the
      trial, similar to the utilization of multiple different MRI platforms in MS
      clinical trials.

PMID- 21853059
TI  - A role for glutamate transporters in the regulation of insulin secretion.
AB  - In the brain, glutamate is an extracellular transmitter that mediates cell-to
      cell communication. Prior to synaptic release it is pumped into vesicles by
      vesicular glutamate transporters (VGLUTs). To inactivate glutamate receptor
      responses after release, glutamate is taken up into glial cells or neurons by
      excitatory amino acid transporters (EAATs). In the pancreatic islets of
      Langerhans, glutamate is proposed to act as an intracellular messenger,
      regulating insulin secretion from beta-cells, but the mechanisms involved are
      unknown. By immunogold cytochemistry we show that insulin containing secretory
      granules express VGLUT3. Despite the fact that they have a VGLUT, the levels of
      glutamate in these granules are low, indicating the presence of a protein that
      can transport glutamate out of the granules. Surprisingly, in beta-cells the
      glutamate transporter EAAT2 is located, not in the plasma membrane as it is in
      brain cells, but exclusively in insulin-containing secretory granules, together
      with VGLUT3. In EAAT2 knock out mice, the content of glutamate in secretory
      granules is higher than in wild type mice. These data imply a glutamate cycle in
      which glutamate is carried into the granules by VGLUT3 and carried out by EAAT2.
      Perturbing this cycle by knocking down EAAT2 expression with a small interfering
      RNA, or by over-expressing EAAT2 or a VGLUT in insulin granules, significantly
      reduced the rate of granule exocytosis. Simulations of granule energetics suggest
      that VGLUT3 and EAAT2 may regulate the pH and membrane potential of the granules
      and thereby regulate insulin secretion. These data suggest that insulin secretion
      from beta-cells is modulated by the flux of glutamate through the secretory
      granules.

PMID- 21853060
TI  - Differential effects of TNF (TNFSF2) and IFN-gamma on intestinal epithelial cell
      morphogenesis and barrier function in three-dimensional culture.
AB  - BACKGROUND: The cytokines TNF (TNFSF2) and IFNgamma are important mediators of
      inflammatory bowel diseases and contribute to enhanced intestinal epithelial
      permeability by stimulating apoptosis and/or disrupting tight junctions.
      Apoptosis and tight junctions are also important for epithelial tissue
      morphogenesis, but the effect of TNF and IFNgamma on the process of intestinal
      epithelial morphogenesis is unknown. METHODS/PRINCIPAL FINDINGS: We have employed
      a three-dimensional cell culture system, reproducing in vivo-like multicellular
      organization of intestinal epithelial cells, to study the effect of TNF on
      intestinal epithelial morphogenesis and permeability. We show that human
      intestinal epithelial cells in three-dimensional culture assembled into luminal
      spheres consisting of a single layer of cells with structural, internal, and
      planar cell polarity. Exposure of preformed luminal spheres to TNF or IFNgamma
      enhanced paracellular permeability, but via distinctive mechanisms. Thus, while
      both TNF and IFNgamma, albeit in a distinguishable manner, induced the
      displacement of selected tight junction proteins, only TNF increased paracellular
      permeability via caspase-driven apoptosis and cell shedding. Infliximab and
      adalumimab inhibited these effects of TNF. Moreover, we demonstrate that TNF via
      its stimulatory effect on apoptosis fundamentally alters the process of
      intestinal epithelial morphogenesis, which contributes to the de novo generation
      of intestinal epithelial monolayers with increased permeability. Also IFNgamma
      contributes to the de novo formation of monolayers with increased permeability,
      but in a manner that does not involve apoptosis. CONCLUSIONS: Our study provides
      an optimized 3D model system for the integrated analysis of (real-time)
      intestinal epithelial paracellular permeability and morphogenesis, and reveals
      apoptosis as a pivotal mechanism underlying the enhanced permeability and altered
      morphogenesis in response to TNF, but not IFNgamma.

PMID- 21853061
TI  - Strategies for reforestation under uncertain future climates: guidelines for
      Alberta, Canada.
AB  - BACKGROUND: Commercial forestry programs normally use locally collected seed for
      reforestation under the assumption that tree populations are optimally adapted to
      local environments. However, in western Canada this assumption is no longer valid
      because of climate trends that have occurred over the last several decades. The
      objective of this study is to show how we can arrive at reforestation
      recommendations with alternative species and genotypes that are viable under a
      majority of climate change scenarios. METHODOLOGY/PRINCIPAL FINDINGS: In a case
      study for commercially important tree species of Alberta, we use an ecosystem
      based bioclimate envelope modeling approach for western North America to project
      habitat for locally adapted populations of tree species using multi-model climate
      projections for the 2020s, 2050s and 2080s. We find that genotypes of species
      that are adapted to drier climatic conditions will be the preferred planting
      stock over much of the boreal forest that is commercially managed. Interestingly,
      no alternative species that are currently not present in Alberta can be
      recommended with any confidence. Finally, we observe large uncertainties in
      projections of suitable habitat that make reforestation planning beyond the 2050s
      difficult for most species. CONCLUSION/SIGNIFICANCE: More than 50,000 hectares of
      forests are commercially planted every year in Alberta. Choosing alternative
      planting stock, suitable for expected future climates, could therefore offer an
      effective climate change adaptation strategy at little additional cost. Habitat
      projections for locally adapted tree populations under observed climate change
      conform well to projections for the 2020s, which suggests that it is a safe
      strategy to change current reforestation practices and adapt to new climatic
      realities through assisted migration prescriptions.

PMID- 21853063
TI  - Strength of word-specific neural memory traces assessed electrophysiologically.
AB  - Memory traces for words are frequently conceptualized neurobiologically as
      networks of neurons interconnected via reciprocal links developed through
      associative learning in the process of language acquisition. Neurophysiological
      reflection of activation of such memory traces has been reported using the
      mismatch negativity brain potential (MMN), which demonstrates an enhanced
      response to meaningful words over meaningless items. This enhancement is believed
      to be generated by the activation of strongly intraconnected long-term memory
      circuits for words that can be automatically triggered by spoken linguistic input
      and that are absent for unfamiliar phonological stimuli. This conceptual
      framework critically predicts different amounts of activation depending on the
      strength of the word's lexical representation in the brain. The frequent use of
      words should lead to more strongly connected representations, whereas less
      frequent items would be associated with more weakly linked circuits. A word with
      higher frequency of occurrence in the subject's language should therefore lead to
      a more pronounced lexical MMN response than its low-frequency counterpart. We
      tested this prediction by comparing the event-related potentials elicited by low-
      and high-frequency words in a passive oddball paradigm; physical stimulus
      contrasts were kept identical. We found that, consistent with our prediction,
      presenting the high-frequency stimulus led to a significantly more pronounced MMN
      response relative to the low-frequency one, a finding that is highly similar to
      previously reported MMN enhancement to words over meaningless pseudowords.
      Furthermore, activation elicited by the higher-frequency word peaked earlier
      relative to low-frequency one, suggesting more rapid access to frequently used
      lexical entries. These results lend further support to the above view on word
      memory traces as strongly connected assemblies of neurons. The speed and
      magnitude of their activation appears to be linked to the strength of internal
      connections in a memory circuit, which is in turn determined by the everyday use
      of language elements.

PMID- 21853062
TI  - Repeated exposure to severely limited sleep results in distinctive and persistent
      physiological imbalances in rats.
AB  - Chronic sleep disruption in laboratory rats leads to increased energy
      expenditure, connective tissue abnormalities, and increased weights of major
      organs relative to body weight. Here we report on expanded findings and the
      extent to which abnormalities become long-lasting, potentially permanent changes
      to health status after apparent recuperation from chronic sleep disruption. Rats
      were exposed 6 times to long periods of disrupted sleep or control conditions
      during 10 weeks to produce adaptations and then were permitted nearly 4 months of
      undisturbed sleep. Measurements were made in tissues from these groups and in
      preserved tissue from the experimental and control groups of an antecedent study
      that lacked a lengthy recuperation period. Cycles of sleep restriction resulted
      in energy deficiency marked by a progressive course of hyperphagia and major
      (15%) weight loss. Analyses of tissue composition in chronically sleep-restricted
      rats indicated that protein and lipid amounts in internal organs were largely
      spared, while adipose tissue depots appeared depleted. This suggests high
      metabolic demands may have preserved the size of the vital organs relative to
      expectations of severe energy deficiency alone. Low plasma corticosterone and
      leptin concentrations appear to reflect low substrate availability and diminished
      adiposity. After nearly 4 months of recuperation, sleep-restricted rats were
      consuming 20% more food and 35% more water than did comparison control rats,
      despite normalized weight, normalized adipocytes, and elevated plasma leptin
      concentrations. Plasma cholesterol levels in recuperated sleep-restricted rats
      were diminished relative to those of controls. The chronically increased intake
      of nutriments and water, along with altered negative feedback regulation and
      substrate use, indicate that internal processes are modified long after a severe
      period of prolonged and insufficient sleep has ended.

PMID- 21853064
TI  - Serologic survey of the pandemic H1N1 2009 virus in Guangdong Province, China: a
      cross sectional study.
AB  - BACKGROUND: Relying on surveillance of clinical cases limits the ability to
      understand the full impact and severity of an epidemic, which urges a deep
      insight into the serological evidence of infection and transmission feature of
      pandemic H1N1 2009 (pH1N1) virus in Guangdong province. METHODS: In this cross
      sectional serological survey, serum samples were collected by multi-stage
      stratified random sampling in Jan 2010. Antibody titers were measured by
      hemagglutination inhibition (HI) assay. Age-specific and region-specific
      prevalence were calculated based on the results of HI assay (positive, HI
      titer>=1:40). RESULTS: A total of 4,319 serum samples had been collected from
      subjects without vaccination with pH1N1 vaccine. The seroprevalence was 22.82%
      (985/4,319). By contrast, there was a marked spatial heterogeneity in prevalence.
      The seroprevalence was 27.3% in large city, 21.4% in medium cities, higher than
      that of 20.2% in rural areas. The seroprevalence was highest in 11-20 age group
      (32.8%), however, in those above 60 years of age group, which was 12.6%, lower
      than other age groups. On the other hand, antibody titers to pH1N1 virus were
      highest in school children, which were followed by a gradual decrease in adult.
      However, in the elderly groups from cities, especially from large city, the
      antibody titer to pH1N1 increased significantly and reached a much higher level.
      CONCLUSION: Our results showed that the prevalence for pH1N1 was correlated with
      age and population density. Preexisting antibody may have protected the very old
      from pH1N1 infection, while original antigenic sin and immunosenescence may have
      contributed to greater severity once infected. These should be considered when
      studying the pathogenesis and transmission of influenza virus and formulating
      strategies on vaccination and treatment.

PMID- 21853065
TI  - Lack of low frequency variants masks patterns of non-neutral evolution following
      domestication.
AB  - Detecting artificial selection in the genome of domesticated species can not only
      shed light on human history but can also be beneficial to future breeding
      strategies. Evidence for selection has been documented in domesticated species
      including maize and rice, but few studies have to date detected signals of
      artificial selection in the Sorghum bicolor genome. Based on evidence that
      domesticated S. bicolor and its wild relatives show significant differences in
      endosperm structure and quality, we sequenced three candidate seed storage
      protein (kafirin) loci and three candidate starch biosynthesis loci to test
      whether these genes show non-neutral evolution resulting from the domestication
      process. We found strong evidence of non-neutral selection at the starch synthase
      IIa gene, while both starch branching enzyme I and the beta kafirin gene showed
      weaker evidence of non-neutral selection. We argue that the power to detect
      consistent signals of non-neutral selection in our dataset is confounded by the
      absence of low frequency variants at four of the six candidate genes. A future
      challenge in the detection of positive selection associated with domestication in
      sorghum is to develop models that can accommodate for skewed frequency spectrums.

PMID- 21853066
TI  - Severe 2010 cold-water event caused unprecedented mortality to corals of the
      Florida reef tract and reversed previous survivorship patterns.
AB  - BACKGROUND: Coral reefs are facing increasing pressure from natural and
      anthropogenic stressors that have already caused significant worldwide declines.
      In January 2010, coral reefs of Florida, United States, were impacted by an
      extreme cold-water anomaly that exposed corals to temperatures well below their
      reported thresholds (16 degrees C), causing rapid coral mortality unprecedented
      in spatial extent and severity. METHODOLOGY/PRINCIPAL FINDINGS: Reef surveys were
      conducted from Martin County to the Lower Florida Keys within weeks of the
      anomaly. The impacts recorded were catastrophic and exceeded those of any
      previous disturbances in the region. Coral mortality patterns were directly
      correlated to in-situ and satellite-derived cold-temperature metrics. These
      impacts rival, in spatial extent and intensity, the impacts of the well
      publicized warm-water bleaching events around the globe. The mean percent coral
      mortality recorded for all species and subregions was 11.5% in the 2010 winter,
      compared to 0.5% recorded in the previous five summers, including years like 2005
      where warm-water bleaching was prevalent. Highest mean mortality (15%-39%) was
      documented for inshore habitats where temperatures were <11 degrees C for
      prolonged periods. Increases in mortality from previous years were significant
      for 21 of 25 coral species, and were 1-2 orders of magnitude higher for most
      species. CONCLUSIONS/SIGNIFICANCE: The cold-water anomaly of January 2010 caused
      the worst coral mortality on record for the Florida Reef Tract, highlighting the
      potential catastrophic impacts that unusual but extreme climatic events can have
      on the persistence of coral reefs. Moreover, habitats and species most severely
      affected were those found in high-coral cover, inshore, shallow reef habitats
      previously considered the "oases" of the region, having escaped declining
      patterns observed for more offshore habitats. Thus, the 2010 cold-water anomaly
      not only caused widespread coral mortality but also reversed prior resistance and
      resilience patterns that will take decades to recover.

PMID- 21853067
TI  - SB202190-induced cell type-specific vacuole formation and defective autophagy do
      not depend on p38 MAP kinase inhibition.
AB  - SB202190, a widely used inhibitor of p38 MAPKalpha and beta, was recently
      described to induce autophagic vacuoles and cell death in colon and ovarian
      cancer cells lines and, therefore, this effect was supposed to be specific for
      transformed cells and to open therapeutic options. Here, we demonstrate that
      SB202190 and the structurally related inhibitor SB203580 induce pro-autophagic
      gene expression and vacuole formation in various cancer and non-cancer cell lines
      of human, rat, mouse and hamster origin. This effect seems to induce defective
      autophagy leading to the accumulation of acidic vacuoles, p62 protein and lipid
      conjugated LC3. Using further p38 inhibitors we show that p38 MAPK inhibition is
      not sufficient for the autophagic response. In line with these results,
      expression of a SB202190-resistant mutant of p38alpha, which significantly
      increases activity of the p38 pathway under inhibitory conditions, does not block
      SB202190-dependent vacuole formation, indicating that lack of p38alpha activity
      is not necessary for this effect. Obviously, the induction of autophagic vacuole
      formation by SB203580 and SB202190 is due to off-target effects of these
      inhibitors on post-translational protein modifications, such as phosphorylation
      of the MAPKs ERK1/2 and JNK1/2, ribosomal protein S6, and PKB/Akt. Interestingly,
      the PI3K-inhibitor wortmannin induces transient vacuole formation indicating that
      the PI3K-PKB/Akt-mTOR pathway is essential for preventing autophagy and that
      cross-inhibition of this pathway by SB202190 could be the reason for the early
      part of the effect observed.

PMID- 21853068
TI  - Prediction of emergent heart failure death by semi-quantitative triage risk
      stratification.
AB  - OBJECTIVES: Generic triage risk assessments are widely used in the emergency
      department (ED), but have not been validated for prediction of short-term risk
      among patients with acute heart failure (HF). Our objective was to evaluate the
      Canadian Triage Acuity Scale (CTAS) for prediction of early death among HF
      patients. METHODS: We included patients presenting with HF to an ED in Ontario
      from Apr 2003 to Mar 2007. We used the National Ambulatory Care Reporting System
      and vital statistics databases to examine care and outcomes. RESULTS: Among
      68,380 patients (76+/-12 years, 49.4% men), early mortality was stratified with
      death rates of 9.9%, 1.9%, 0.9%, and 0.5% at 1-day, and 17.2%, 5.9%, 3.8%, and
      2.5% at 7-days, for CTAS 1, 2, 3, and 4-5, respectively. Compared to lower acuity
      (CTAS 4-5) patients, adjusted odds ratios (aOR) for 1-day death were 1.32 (95%CI;
      0.93-1.88; p = 0.12) for CTAS 3, 2.41 (95%CI; 1.71-3.40; p<0.001) for CTAS 2, and
      highest for CTAS 1: 9.06 (95%CI; 6.28-13.06; p<0.001). Predictors of triage
      critical (CTAS 1) status included oxygen saturation <90% (aOR 5.92, 95%CI; 3.09
      11.81; p<0.001), respiratory rate >24 breaths/minute (aOR 1.96, 95%CI; 1.05-3.67;
      p = 0.034), and arrival by paramedic (aOR 3.52, 95%CI; 1.70-8.02; p = 0.001).
      While age/sex-adjusted CTAS score provided good discrimination for ED (c
      statistic = 0.817) and 1-day (c-statistic = 0.724) death, mortality prediction
      was improved further after accounting for cardiac and non-cardiac co-morbidities
      (c-statistics 0.882 and 0.810, respectively; both p<0.001). CONCLUSIONS: A semi
      quantitative triage acuity scale assigned at ED presentation and based largely on
      respiratory factors predicted emergent death among HF patients.

PMID- 21853069
TI  - Technical modifications of double-J stenting for retroperitoneal laparoscopic
      dismembered pyeloplasty in children under 5 years old.
AB  - Both antegrade stenting and retrograde stenting for retroperitoneal laparoscopic
      dismembered pyeloplasty in children have many disadvantages. In this work, we
      tried using an alternative technique of modified antegrade (MAG) double-J
      stenting for retroperitoneal laparoscopic dismembered pyeloplasty in children
      under 5 years old, analyzed our results using the conventional antegrade (CAG)
      and the MAG techniques of stent insertion for this procedure, and reported our
      experience with these techniques. Between December 2002 and July 2010, 77
      children under 5 years old with ureteropelvic junction obstruction underwent
      retroperitoneal laparoscopic dismembered pyeloplasty. CAG and MAG double-J
      stenting were attempted, in the first 36 cases (mean age 27.1 months) and the
      following 41 cases (mean age 25.4 months), respectively. The stents were removed
      4-6 weeks later via cystoscopy. Follow-up studies were performed with
      ultrasonography and intravenous urography at 3 and 12 months postoperatively. The
      results showed that successful stent placement without malpositioning was
      achieved in 31 of 36 (86%) and all 41 (100%) cases, in the CAG and MAG groups,
      respectively. The common factor of unsuccessful stent was the inability to across
      the ureterovesical junction. The mean stent insertion time was 10 min 54 s and 12
      min 46 s in the CAG and MAG groups, respectively. The mean operating time was 176
      min and 185 min in the CAG and MAG groups, respectively. No stent malpositioning
      occurred in the MAG group; in the CAG group, two children had a malpositioned
      stent in the distal ureter and one child presented with a severe hematuria.
      Twelve months follow-up showed no new onset of hydroureteronephrosis and
      hydronephrosis. Thus we concluded that the MAG double-J stenting seems more
      reliable than CAG stenting for retroperitoneal laparoscopic dismembered
      pyeloplasty in children under 5 years old, with greater success and lower
      complication rates.

PMID- 21853070
TI  - Production of a bioengineered G-protein coupled receptor of human formyl peptide
      receptor 3.
AB  - G-protein coupled receptors (GPCRs) participate in a wide range of vital
      regulations of our physiological actions. They are also of pharmaceutical
      importance and have become many therapeutic targets for a number of disorders and
      diseases. Purified GPCR-based approaches including structural study and novel
      biophysical and biochemical function analyses are increasingly being used in GPCR
      directed drug discovery. Before these approaches become routine, however, several
      hurdles need to be overcome; they include overexpression, solubilization, and
      purification of large quantities of functional and stable receptors on a regular
      basis. Here we report milligram production of a human formyl peptide receptor 3
      (FPR3). FPR3 comprises a functionally distinct GPCR subfamily that is involved in
      leukocyte chemotaxis and activation. The bioengineered FPR3 was overexpressed in
      stable tetracycline-inducible mammalian cell lines (HEK293S). After a systematic
      detergent screening, fos-choline-14 (FC-14) was selected for subsequent
      solubilization and purification processes. A two-step purification method,
      immunoaffinity using anti-rho-tag monoclonal antibody 1D4 and gel filtration, was
      used to purify the receptors to near homogeneity. Immunofluorescence analysis
      showed that expressed FPR3 was predominantly displayed on cellular membrane.
      Secondary structural analysis using circular dichroism showed that the purified
      FPR3 receptor was correctly folded with >50% alpha-helix, which is similar to
      other known GPCR secondary structures. Our method can readily produce milligram
      quantities of human FPR3, which would facilitate in developing human FPR as
      therapeutic drug targets.

PMID- 21853071
TI  - A new model using routinely available clinical parameters to predict significant
      liver fibrosis in chronic hepatitis B.
AB  - OBJECTIVE: We developed a predictive model for significant fibrosis in chronic
      hepatitis B (CHB) based on routinely available clinical parameters. METHODS: 237
      treatment-naive CHB patients [58.4% hepatitis B e antigen (HBeAg)-positive] who
      had undergone liver biopsy were randomly divided into two cohorts: training group
      (n = 108) and validation group (n = 129). Liver histology was assessed for
      fibrosis. All common demographics, viral serology, viral load and liver
      biochemistry were analyzed. RESULTS: Based on 12 available clinical parameters
      (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP,
      GGT and AFP), a model to predict significant liver fibrosis (Ishak fibrosis score
      >=3) was derived using the five best parameters (age, ALP, AST, AFP and
      platelet). Using the formula log(index+1) = 0.025+0.0031(age)+0.1483
      log(ALP)+0.004 log(AST)+0.0908 log(AFP+1)-0.028 log(platelet), the PAPAS
      (Platelet/Age/Phosphatase/AFP/AST) index predicts significant fibrosis with an
      area under the receiving operating characteristics (AUROC) curve of 0.776 [0.797
      for patients with ALT <2*upper limit of normal (ULN)] The negative predictive
      value to exclude significant fibrosis was 88.4%. This predictive power is
      superior to other non-invasive models using common parameters, including the
      AST/platelet/GGT/AFP (APGA) index, AST/platelet ratio index (APRI), and the FIB-4
      index (AUROC of 0.757, 0.708 and 0.723 respectively). Using the PAPAS index,
      67.5% of liver biopsies for patients being considered for treatment with ALT
      <2*ULN could be avoided. CONCLUSION: The PAPAS index can predict and exclude
      significant fibrosis, and may reduce the need for liver biopsy in CHB patients.

PMID- 21853072
TI  - Early potent protection against heterologous SIVsmE660 challenge following live
      attenuated SIV vaccination in Mauritian cynomolgus macaques.
AB  - BACKGROUND: Live attenuated simian immunodeficiency virus (SIV) vaccines
      represent the most effective means of vaccinating macaques against pathogenic SIV
      challenge. However, thus far, protection has been demonstrated to be more
      effective against homologous than heterologous strains. Immune correlates of
      vaccine-induced protection have also been difficult to identify, particularly
      those measurable in the peripheral circulation. METHODOLOGY/PRINCIPAL FINDINGS:
      Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus
      macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned
      SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8.
      MCM provided a characterised host genetic background with limited Major
      Histocompatibility Complex (MHC) and TRIM5alpha allelic diversity. Early
      protection, observed as soon as 3 weeks post-vaccination, was comparable to that
      of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in
      breakthrough cases where simultaneous identification of vaccine and challenge
      viruses by virus-specific PCR was indicative of active co-infection. Persistence
      of the vaccine virus in a range of lymphoid tissues was typified by a consistent
      level of SIV RNA positive cells in protected vaccinates. However, no association
      between MHC class I/II haplotype or TRIM5alpha polymorphism and study outcome was
      identified. CONCLUSION/SIGNIFICANCE: This SIV vaccine study, conducted in MHC
      characterised MCM, demonstrated potent protection against the pathogenic,
      heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level
      of protection against this viral stock by intravenous challenge has not been
      hitherto observed. The mechanism(s) of protection by vaccination with live
      attenuated SIV must account for the heterologous and early protection data
      described in this study, including those which relate to the innate immune
      system.

PMID- 21853073
TI  - The effect of the potential PhoQ histidine kinase inhibitors on Shigella flexneri
      virulence.
AB  - PhoQ/PhoP is an important two-component system that regulates Shigella virulence.
      We explored whether the PhoQ/PhoP system is a promising target for new
      antibiotics against S. flexneri infection. By using a high-throughput screen and
      enzymatic activity coupled assay, four compounds were found as potential PhoQ
      inhibitors. These compounds not only inhibited the activity of SF-PhoQc
      autophosphorylation but also displayed high binding affinities to the SF-PhoQc
      protein in the Surface Plasmon Resonance response. A S. flexneri cell invasion
      assay showed that three of these potential PhoQ inhibitors inhibit the invasion
      of HeLa cells by S. flexneri 9380. In a Mouse Sereny test, mice inoculated with
      S. flexneri 9380 pre-treated with the potential PhoQ inhibitors 1, 2, 3 or 4
      displayed no inflammation, whereas mice inoculated with S. flexneri 9380 alone
      displayed severe keratoconjunctival inflammation. All four potential PhoQ
      inhibitors showed no significant cytotoxicity or hemolytic activity. These data
      suggest that the four potential PhoQ inhibitors inhibited the virulence of S.
      flexneri and that PhoQ/PhoP is a promising target for the development of drugs
      against S. flexneri infection.

PMID- 21853074
TI  - Concealed fertility and extended female sexuality in a non-human primate (Macaca
      assamensis).
AB  - In numerous primates living in mixed-sex groups, females display probabilistic
      cues of fertility to simultaneously concentrate paternity to dominant males while
      diluting it amongst others as a means to reduce the risk of infanticide and to
      increase male care for offspring. A few species, however, lack these cues and
      potentially conceal fertility from males; yet, to date, little is known about
      mating patterns and their underlying proximate mechanisms in such species. Here,
      we investigated mating activity and sexual consortships relative to female
      reproductive state in wild Assamese macaques (Macaca assamensis), a species where
      females lack prominent anogenital swellings and copulation calls. During two
      mating seasons (2837 contact hours) we recorded sexual and social behaviors,
      sexual consortships, and collected 1178 fecal samples (n = 15 females) which were
      analyzed for progestogen concentrations to assess female reproductive state and
      to determine the timing of ovulation and conception. Although mostly conceiving
      in their first ovarian cycle, females were sexually receptive throughout the
      entire 4-month mating season, and within-cycle mating frequencies were not
      increased during fertile phases. Dominant males did not monopolize fertile
      matings, and consortships by high-ranking males lasted for long periods, which
      were not exclusively linked to female fertile phases. Furthermore, females
      copulated promiscuously but not randomly, i.e. for almost every female, matings
      were concentrated to a certain male, irrespective of male rank. Collectively, we
      demonstrate that fertility is undisclosed to males. The extreme extended female
      sexuality facilitated by concealed fertility may allow females to create
      differentiated mating relationships within a promiscuous mating system. Our study
      provides important new insight into the plasticity of female sexuality in non
      human primates.

PMID- 21853075
TI  - Aortic wave dynamics and its influence on left ventricular workload.
AB  - The pumping mechanism of the heart is pulsatile, so the heart generates pulsatile
      flow that enters into the compliant aorta in the form of pressure and flow waves.
      We hypothesized that there exists a specific heart rate at which the external
      left ventricular (LV) power is minimized. To test this hypothesis, we used a
      computational model to explore the effects of heart rate (HR) and aortic rigidity
      on left ventricular (LV) power requirement. While both mean and pulsatile parts
      of the pressure play an important role in LV power requirement elevation, at
      higher rigidities the effect of pulsatility becomes more dominant. For any given
      aortic rigidity, there exists an optimum HR that minimizes the LV power
      requirement at a given cardiac output. The optimum HR shifts to higher values as
      the aorta becomes more rigid. To conclude, there is an optimum condition for
      aortic waves that minimizes the LV pulsatile load and consequently the total LV
      workload.

PMID- 21853076
TI  - Pronounced hypoxia in models of murine and human leukemia: high efficacy of
      hypoxia-activated prodrug PR-104.
AB  - Recent studies indicate that interactions between leukemia cells and the bone
      marrow (BM) microenvironment promote leukemia cell survival and confer resistance
      to anti-leukemic drugs. There is evidence that BM microenvironment contains
      hypoxic areas that confer survival advantage to hematopoietic cells. In the
      present study we investigated whether hypoxia in leukemic BM contributes to the
      protective role of the BM microenvironment. We observed a marked expansion of
      hypoxic BM areas in immunodeficient mice engrafted with acute lymphoblastic
      leukemia (ALL) cells. Consistent with this finding, we found that hypoxia
      promotes chemoresistance in various ALL derived cell lines. These findings
      suggest to employ hypoxia-activated prodrugs to eliminate leukemia cells within
      hypoxic niches. Using several xenograft models, we demonstrated that
      administration of the hypoxia-activated dinitrobenzamide mustard, PR-104
      prolonged survival and decreased leukemia burden of immune-deficient mice
      injected with primary acute lymphoblastic leukemia cells. Together, these
      findings strongly suggest that targeting hypoxia in leukemic BM is feasible and
      may significantly improve leukemia therapy.

PMID- 21853077
TI  - Influence of stochastic gene expression on the cell survival rheostat after
      traumatic brain injury.
AB  - Experimental evidence suggests that random, spontaneous (stochastic) fluctuations
      in gene expression have important biological consequences, including
      determination of cell fate and phenotypic variation within isogenic populations.
      We propose that fluctuations in gene expression represent a valuable tool to
      explore therapeutic strategies for patients who have suffered traumatic brain
      injury (TBI), for which there is no effective drug therapy. We have studied the
      effects of TBI on the hippocampus because TBI survivors commonly suffer cognitive
      problems that are associated with hippocampal damage. In our previous studies we
      separated dying and surviving hippocampal neurons by laser capture
      microdissection and observed unexplainable variations in post-TBI gene
      expression, even though dying and surviving neurons were adjacent and
      morphologically identical. We hypothesized that, in hippocampal neurons that
      subsequently are subjected to TBI, randomly increased pre-TBI expression of genes
      that are associated with neuroprotection predisposes neurons to survival;
      conversely, randomly decreased expression of these genes predisposes neurons to
      death. Thus, to identify genes that are associated with endogenous
      neuroprotection, we performed a comparative, high-resolution transcriptome
      analysis of dying and surviving hippocampal neurons in rats subjected to TBI. We
      found that surviving hippocampal neurons express a distinct molecular signature-
      increased expression of networks of genes that are associated with regeneration,
      cellular reprogramming, development, and synaptic plasticity. In dying neurons we
      found decreased expression of genes in those networks. Based on these data, we
      propose a hypothetical model in which hippocampal neuronal survival is determined
      by a rheostat that adds injury-induced genomic signals to expression of pro
      survival genes, which pre-TBI varies randomly and spontaneously from neuron to
      neuron. We suggest that pharmacotherapeutic strategies that co-activate multiple
      survival signals and enhance self-repair mechanisms have the potential to shift
      the cell survival rheostat to favor survival and therefore improve functional
      outcome after TBI.

PMID- 21853078
TI  - The impact of preoperative hip heterotopic ossification extent on recurrence in
      patients with head and spinal cord injury: a case control study.
AB  - BACKGROUND: The preoperative Heterotopic Ossification (HO) extent is usually one
      of the main used criteria to predict the recurrence before excision. Brooker et
      al built a radiologic scale to assess this pre operative extent around the hip.
      The aim of this study is to investigate the relationship between the recurrence
      risk after hip HO excision in Traumatic Brain Injury (TBI) and Spinal Cord Injury
      (SCI) patients and the preoperative extent of HO. METHODOLOGY/PRINCIPAL FINDINGS:
      A case control study including TBI or SCI patients following surgery for
      troublesome hip HO with (case, n = 19) or without (control, n = 76) recurrence.
      Matching criteria were: sex, pathology (SCI or TBI) and age at the time of
      surgery (+/-4.5 years). For each etiology (TBI and SCI), the residual cognitive
      and functional status (Garland classification), the preoperative extent (Brooker
      status), the modified radiological and functional status (GCG-BD classification),
      HO localization, side, mean age at the CNS damage, mean delay for the first HO
      surgery, and for the case series, the mean operative delay for recurrence after
      the first surgical intervention were noted. CONCLUSIONS/SIGNIFICANCE: The median
      delay for first HO surgery was 38.6 months (range 4.5 to 414.5;) for the case
      subgroup and 17.6 months (range 5.7 to 339.6) for the control group. No
      significant link was found between recurrence and operative delay (p = 0.51); the
      location around the joint (0.07); the Brooker (p = 0.52) or GCG-BD status (p =
      0.79). Including all the matching factors, no significant relationship was found
      between the recurrence HO risk and the preoperative extent of troublesome hip HO
      using Brooker status (OR = 1.56(95% CI: 0.47-5.19)) or GCG-BD status (OR class 3
      versus 2 = 0.67(95% CI: 0.11-4.24) and OR class 4 versus 2 = 0.79(95%CI: 0.09
      6.91)). Until the pathophysiology of HO development is understood, it will be
      difficult to create tools which can predict HO recurrence.

PMID- 21853079
TI  - Prediction of thermostability from amino acid attributes by combination of
      clustering with attribute weighting: a new vista in engineering enzymes.
AB  - The engineering of thermostable enzymes is receiving increased attention. The
      paper, detergent, and biofuel industries, in particular, seek to use
      environmentally friendly enzymes instead of toxic chlorine chemicals. Enzymes
      typically function at temperatures below 60 degrees C and denature if exposed to
      higher temperatures. In contrast, a small portion of enzymes can withstand higher
      temperatures as a result of various structural adaptations. Understanding the
      protein attributes that are involved in this adaptation is the first step toward
      engineering thermostable enzymes. We employed various supervised and unsupervised
      machine learning algorithms as well as attribute weighting approaches to find
      amino acid composition attributes that contribute to enzyme thermostability.
      Specifically, we compared two groups of enzymes: mesostable and thermostable
      enzymes. Furthermore, a combination of attribute weighting with supervised and
      unsupervised clustering algorithms was used for prediction and modelling of
      protein thermostability from amino acid composition properties. Mining a large
      number of protein sequences (2090) through a variety of machine learning
      algorithms, which were based on the analysis of more than 800 amino acid
      attributes, increased the accuracy of this study. Moreover, these models were
      successful in predicting thermostability from the primary structure of proteins.
      The results showed that expectation maximization clustering in combination with
      uncertainly and correlation attribute weighting algorithms can effectively (100%)
      classify thermostable and mesostable proteins. Seventy per cent of the weighting
      methods selected Gln content and frequency of hydrophilic residues as the most
      important protein attributes. On the dipeptide level, the frequency of Asn-Glu
      was the key factor in distinguishing mesostable from thermostable enzymes. This
      study demonstrates the feasibility of predicting thermostability irrespective of
      sequence similarity and will serve as a basis for engineering thermostable
      enzymes in the laboratory.

PMID- 21853081
TI  - Latitudinal range influences the seasonal variation in the foraging behavior of
      marine top predators.
AB  - Non-migratory resident species should be capable of modifying their foraging
      behavior to accommodate changes in prey abundance and availability associated
      with a changing environment. Populations that are better adapted to change will
      have higher foraging success and greater potential for survival in the face of
      climate change. We studied two species of resident central place foragers from
      temperate and equatorial regions with differing population trends and prey
      availability associated to season, the California sea lion (Zalophus
      californianus) (CSL) whose population is increasing and the endangered Galapagos
      sea lion (Zalophus wollebaeki) (GSL) whose population is declining. To determine
      their response to environmental change, we studied and compared their diving
      behavior using time-depth recorders and satellite location tags and their diet by
      measuring C and N isotope ratios during a warm and a cold season. Based on
      latitudinal differences in oceanographic productivity, we hypothesized that the
      seasonal variation in foraging behavior would differ for these two species. CSL
      exhibited greater seasonal variability in their foraging behavior as seen in
      changes to their diving behavior, foraging areas and diet between seasons.
      Conversely, GSL did not change their diving behavior between seasons, presenting
      three foraging strategies (shallow, deep and bottom divers) during both. GSL
      exhibited greater dive and foraging effort than CSL. We suggest that during the
      warm and less productive season a greater range of foraging behaviors in CSL was
      associated with greater competition for prey, which relaxed during the cold
      season when resource availability was greater. GSL foraging specialization
      suggests that resources are limited throughout the year due to lower primary
      production and lower seasonal variation in productivity compared to CSL. These
      latitudinal differences influence their foraging success, pup survival and
      population growth reflected in contrasting population trends in which CSL are
      more successful and potentially more resilient to climate change.

PMID- 21853080
TI  - Characterization of Salmonella occurring at high prevalence in a population of
      the land iguana Conolophus subcristatus in Galapagos Islands, Ecuador.
AB  - The aim of the study was to elucidate the association between the zoonotic
      pathogen Salmonella and a population of land iguana, Colonophus subcristatus,
      endemic to Galapagos Islands in Ecuador. We assessed the presence of Salmonella
      subspecies and serovars and estimated the prevalence of the pathogen in that
      population. Additionally, we investigated the genetic relatedness among isolates
      and serovars utilising pulsed field gel electrophoresis (PFGE) on XbaI-digested
      DNA and determined the antimicrobial susceptibility to a panel of antimicrobials.
      The study was carried out by sampling cloacal swabs from animals (n = 63) in
      their natural environment on in the island of Santa Cruz. A high prevalence
      (62/63, 98.4%) was observed with heterogeneity of Salmonella subspecies and
      serovars, all known to be associated with reptiles and with reptile-associated
      salomonellosis in humans. Serotyping revealed 14 different serovars among four
      Salmonella enterica subspecies: S. enterica subsp. enterica (n = 48), S. enterica
      subsp. salamae (n = 2), S. enterica subsp. diarizonae (n = 1), and S. enterica
      subsp. houtenae (n = 7). Four serovars were predominant: S. Poona (n = 18), S.
      Pomona (n = 10), S. Abaetetuba (n = 8), and S. Newport (n = 5). The S. Poona
      isolates revealed nine unique XbaI PFGE patterns, with 15 isolates showing a
      similarity of 70%. Nine S. Pomona isolates had a similarity of 84%. One main
      cluster with seven (88%) indistinguishable isolates of S. Abaetetuba was
      observed. All the Salmonella isolates were pan-susceptible to antimicrobials
      representative of the most relevant therapeutic classes. The high prevalence and
      absence of clinical signs suggest a natural interaction of the different
      Salmonella serovars with the host species. The interaction may have been
      established before any possible exposure of the iguanas and the biocenosis to
      direct or indirect environmental factors influenced by the use of antimicrobials
      in agriculture, in human medicine or in veterinary medicine.

PMID- 21853082
TI  - Phosphatase-coupled universal kinase assay and kinetics for first-order-rate
      coupling reaction.
AB  - Kinases use adenosine-5'-triphosphate (ATP) as the donor substrate and generate
      adenosine-5'-diphosphate (ADP) as a product. An ADP-based phosphatase-coupled
      kinase assay is described here. In this assay, CD39L2, a nucleotidase, is added
      into a kinase reaction to hydrolyze ADP to AMP and phosphate. The phosphate is
      subsequently detected using malachite green phosphate-detection reagents. As ADP
      hydrolysis by CD39L2 displays a first-order rate constant, relatively simple
      equations are derived to calculate the coupling rate and the lagging time of the
      coupling reaction, allowing one to obtain kinase kinetic parameters without the
      completion of the coupling reaction. ATP inhibition of CD39L2-catalyzed ADP
      hydrolysis is also determined for correction of the kinetic data. As examples,
      human glucokinase, P. chrysogenum APS kinase and human ERK1, kinases specific for
      sugar, nucleotide and protein respectively, are assayed. To assess the
      compatibility of the method for high-throughput assays, Z' factors >0.5 are also
      obtained for the three kinases.

PMID- 21853083
TI  - Why don't you try harder? An investigation of effort production in major
      depression.
AB  - Depression is mainly characterized as an emotional disorder, associated with
      reduced approach behavior. It remains unclear whether the difficulty in
      energising behavior relates to abnormal emotional states or to a flattened
      response to potential rewards, as suggested by several neuroimaging studies.
      Here, we aimed to demonstrate a specific incentive motivation deficit in major
      depression, independent of patients' emotional state. We employed a behavioral
      paradigm designed to measure physical effort in response to both emotional
      modulation and incentive motivation. Patients did exert more effort following
      emotionally arousing pictures (whether positive or negative) but not for higher
      monetary incentives, contrary to healthy controls. These results show that
      emotional and motivational sources of effort production are dissociable in
      pathological conditions. In addition, patients' ratings of perceived effort
      increased for high incentives, whereas controls' ratings were decreased. Thus,
      depressed patients objectively behave as if they do not want to gain larger
      rewards, but subjectively feel that they try harder. We suggest that incentive
      motivation impairment is a core deficit of major depression, which may render
      everyday tasks abnormally effortful for patients.

PMID- 21853084
TI  - ADP-ribosylation factor 6 mediates E-cadherin recovery by chemical chaperones.
AB  - E-cadherin plays a powerful tumor suppressor role. Germline E-cadherin mutations
      justify 30% of Hereditary Diffuse Gastric Cancer (HDGC) and missense mutations
      are found in 30% of these families. We found possible to restore in vitro mutant
      E-cadherin associated to HDGC syndrome by using Chemical Chaperones (CCs).
      Herein, our aim was to disclose the molecular mechanisms underlying the CCs
      effects in E-cadherin regulation. Using cells stably expressing WT E-cadherin or
      two HDGC-associated missense mutations, we show that upon DMSO treatment, not
      only mutant E-cadherin is restored and stabilized at the plasma membrane (PM),
      but also Arf6 and PIPKIgamma expressions are altered. We show that modulation of
      Arf6 expression partially mimics the effect of CCs, suggesting that the cellular
      effects observed upon CCs treatment are mediated by Arf6. Further, we show that E
      cadherin expression recovery is specifically linked to Arf6 due to its role on
      endocytosis and recycling pathways. Finally, we demonstrated that, as DMSO,
      several others CCs are able to modulate the trafficking machinery through an Arf6
      dependent mechanism. Interestingly, the more effective compounds in E-cadherin
      recovery to PM are those that simultaneously inhibit Arf6 and stimulate
      PIPKIgamma expression and binding to E-cadherin. Here, we present the first
      evidence of a direct influence of CCs in cellular trafficking machinery and we
      show that this effect is of crucial importance in the context of juxtamembrane E
      cadherin missense mutations associated to HDGC. We propose that this influence
      should be taken into account when exploring the therapeutic potential of this
      type of chemicals in genetic diseases associated to protein-misfolding.

PMID- 21853085
TI  - Site-specific risk factors for colorectal cancer in a Korean population.
AB  - We investigated the association of colorectal cancer risk factors with different
      colorectal cancer subsites to assess etiological differences for cancers of the
      proximal colon, distal colon, and rectum. Included in this study were 869,725 men
      and 395,501 women who participated in a health examination provided by the Korean
      National Health System between 1996 and 1997. During up to 7 years of follow-up,
      4,144 incident colorectal cancer cases were detected (3,051 men and 1,093 women).
      Greater height was associated with elevated risk for distal colon cancer and
      rectal cancer in both men and women. Family history of cancer was associated with
      higher risk for cancers of the proximal colon in men and distal colon in both men
      and women. Frequent alcohol consumption and consuming high amounts of alcohol
      were associated with elevated risk for distal colon cancer in men and higher risk
      for rectal cancer in women. Frequent meat consumption was associated with risk
      for proximal colon cancer in men and for rectal cancer in women. Our findings
      suggest that risk factors for colorectal cancer are different by subsites of
      colon and rectum, as well as by sex.

PMID- 21853086
TI  - The nucleotide exchange factor Ric-8A is a chaperone for the conformationally
      dynamic nucleotide-free state of Galphai1.
AB  - Heterotrimeric G protein alpha subunits are activated upon exchange of GDP for
      GTP at the nucleotide binding site of Galpha, catalyzed by guanine nucleotide
      exchange factors (GEFs). In addition to transmembrane G protein-coupled receptors
      (GPCRs), which act on G protein heterotrimers, members of the family cytosolic
      proteins typified by mammalian Ric-8A are GEFs for Gi/q/12/13-class Galpha
      subunits. Ric-8A binds to Galpha*GDP, resulting in the release of GDP. The Ric-8A
      complex with nucleotide-free Galphai1 is stable, but dissociates upon binding of
      GTP to Galphai1. To gain insight into the mechanism of Ric-8A-catalyzed GDP
      release from Galphai1, experiments were conducted to characterize the physical
      state of nucleotide-free Galphai1 (hereafter referred to as Galphai1[ ]) in
      solution, both as a monomeric species, and in the complex with Ric-8A. We found
      that Ric-8A-bound, nucleotide-free Galphai1 is more accessible to trypsinolysis
      than Galphai1*GDP, but less so than Galphai1[ ] alone. The TROSY-HSQC spectrum of
      [(15)N]Galphai1[ ] bound to Ric-8A shows considerable loss of peak intensity
      relative to that of [(15)N]Galphai1*GDP. Hydrogen-deuterium exchange in Galphai1[
      ] bound to Ric-8A is 1.5-fold more extensive than in Galphai1*GDP. Differential
      scanning calorimetry shows that both Ric-8A and Galphai1*GDP undergo cooperative,
      irreversible unfolding transitions at 47 degrees  and 52 degrees , respectively,
      while nucleotide-free Galphai1 shows a broad, weak transition near 35 degrees .
      The unfolding transition for Ric-8A:Galphai1[ ] is complex, with a broad
      transition that peaks at 50 degrees , suggesting that both Ric-8A and Galphai1[ ]
      are stabilized within the complex, relative to their respective free states. The
      C-terminus of Galphai1 is shown to be a critical binding element for Ric-8A, as
      is also the case for GPCRs, suggesting that the two types of GEF might promote
      nucleotide exchange by similar mechanisms, by acting as chaperones for the
      unstable and dynamic nucleotide-free state of Galpha.

PMID- 21853087
TI  - Management of metformin-associated lactic acidosis by continuous renal
      replacement therapy.
AB  - BACKGROUND: Metformin-associated lactic acidosis (MALA) is a severe metabolic
      failure with high related mortality. Although its use is controversial,
      intermittent hemodialysis is reported to be the most frequently used treatment in
      conjunction with nonspecific supportive measures. Our aim was to report the
      evolution and outcome of cases managed by continuous renal replacement therapy
      (CRRT). METHODOLOGY AND PRINCIPAL FINDINGS: Over a 3-year period, we
      retrospectively identified patients admitted to the intensive care unit for
      severe lactic acidosis caused by metformin. We included patients in our study who
      were treated with CRRT because of shock. We describe their clinical and
      biological features at admission and during renal support, as well as their
      evolution. We enrolled six patients with severe lactic acidosis; the mean pH and
      mean lactate was 6.92+/-0.20 and 14.4+/-5.1 mmol/l, respectively. Patients had
      high illness severity scores, including the Simplified Acute Physiology Score II
      (SAPS II) (average score 63+/-12 points). Early CRRT comprised either venovenous
      hemofiltration (n = 3) or hemodiafiltration (n = 3) with a mean effluent flow
      rate of 34+/-6 ml/kg/h. Metabolic acidosis control and metformin elimination was
      rapid and there was no rebound. Outcome was favorable in all cases. CONCLUSIONS
      AND SIGNIFICANCE: Standard use of CRRT efficiently treated MALA in association
      with symptomatic organ supportive therapies.

PMID- 21853088
TI  - Integration of spectral reflectance across the plumage: implications for mating
      patterns.
AB  - BACKGROUND: In complex sexual signaling systems such as plumage color,
      developmental or genetic links may occur among seemingly distinct traits.
      However, the interrelations of such traits and the functional significance of
      their integration rarely have been examined. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated the parallel variation of two reflectance descriptors (brightness
      and UV chroma) across depigmented and melanized plumage areas of collared
      flycatchers (Ficedula albicollis), and the possible role of integrated color
      signals in mate acquisition. We found moderate integration in brightness and UV
      chroma across the plumage, with similar correlation structures in the two sexes
      despite the strong sexual dichromatism. Patterns of parallel color change across
      the plumage were largely unrelated to ornamental white patch sizes, but they all
      showed strong assortative mating between the sexes. Comparing different types of
      assortative mating patterns for individual spectral variables suggested a
      distinct role for plumage-level color axes in mate acquisition.
      CONCLUSIONS/SIGNIFICANCE: Our results indicate that the plumage-level, parallel
      variation of coloration might play a role in mate acquisition. This study
      underlines the importance of considering potential developmental and functional
      integration among apparently different ornaments in studies of sexual selection.

PMID- 21853089
TI  - Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by
      direct genome sequencing from peripheral blood of malaria patients.
AB  - Naturally acquired blood-stage infections of the malaria parasite Plasmodium
      falciparum typically harbour multiple haploid clones. The apparent number of
      clones observed in any single infection depends on the diversity of the
      polymorphic markers used for the analysis, and the relative abundance of rare
      clones, which frequently fail to be detected among PCR products derived from
      numerically dominant clones. However, minority clones are of clinical interest as
      they may harbour genes conferring drug resistance, leading to enhanced survival
      after treatment and the possibility of subsequent therapeutic failure. We
      deployed new generation sequencing to derive genome data for five non-propagated
      parasite isolates taken directly from 4 different patients treated for clinical
      malaria in a UK hospital. Analysis of depth of coverage and length of sequence
      intervals between paired reads identified both previously described and novel
      gene deletions and amplifications. Full-length sequence data was extracted for 6
      loci considered to be under selection by antimalarial drugs, and both known and
      previously unknown amino acid substitutions were identified. Full mitochondrial
      genomes were extracted from the sequencing data for each isolate, and these are
      compared against a panel of polymorphic sites derived from published or
      unpublished but publicly available data. Finally, genome-wide analysis of clone
      multiplicity was performed, and the number of infecting parasite clones estimated
      for each isolate. Each patient harboured at least 3 clones of P. falciparum by
      this analysis, consistent with results obtained with conventional PCR analysis of
      polymorphic merozoite antigen loci. We conclude that genome sequencing of
      peripheral blood P. falciparum taken directly from malaria patients provides high
      quality data useful for drug resistance studies, genomic structural analyses and
      population genetics, and also robustly represents clonal multiplicity.

PMID- 21853090
TI  - RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell
      activation.
AB  - BACKGROUND: Programmed necrosis/necroptosis is an emerging form of cell death
      that plays important roles in mammalian development and the immune system. The
      pro-necrotic kinases in the receptor interacting protein (RIP) family are crucial
      mediators of programmed necrosis. Recent advances in necrosis research have been
      greatly aided by the identification of chemical inhibitors that block programmed
      necrosis. Necrostatin-1 (Nec-1) and its derivatives were previously shown to
      target the pro-necrotic kinase RIP1/RIPK1. The protective effect conferred by Nec
      1 and its derivatives in many experimental model systems was often attributed to
      the inhibition of RIP1 function. METHODOLOGY/PRINCIPAL FINDINGS: We compared the
      effect of Nec-1 and siRNA-mediated silencing of RIP1 in the murine fibrosarcoma
      cell line L929. Treatment of L929 cells with the pan-caspase inhibitor zVAD-fmk
      or exogenous TNF induces necrosis. Strikingly, we found that siRNA-mediated
      silencing of RIP1 inhibited zVAD-fmk induced necrosis, but not TNF-induced
      necrosis. TNF-induced cell death in RIP1 knocked down L929 cells was inhibited by
      Nec-1, but not the caspase inhibitor zVAD-fmk. We found that PKA-CS expression,
      but not Jnk or Erk activation, was moderately inhibited by Nec-1. Moreover, we
      found that Nec-1 inhibits proximal T cell receptor signaling independent of RIP1,
      leading to inhibition of T cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our
      results reveal that besides RIP1, Nec-1 also targets other factors crucial for
      necrosis induction in L929 cells. In addition, high doses of Nec-1 inhibit other
      signal transduction pathways such as that for T cell receptor activation. These
      results highlight the importance to independently validate results obtained using
      Nec-1 with other approaches such as siRNA-mediated gene silencing. We propose
      that some of the previous published results obtained using Nec-1 should be re
      evaluated in light of our findings.

PMID- 21853091
TI  - Hypertensive patients show delayed wound healing following total hip
      arthroplasty.
AB  - BACKGROUND: Prolonged wound-discharge following total hip arthroplasty (THA) is
      associated with an increased risk of infection. However, the potential role of
      hypertension in prolonging the duration of wound healing in this population has
      not yet been investigated. The aim of the present study was to compare healing in
      this population that has not yet been investigated. The aim of the present study
      was to compare hypertensive and normotensive THA patients in terms of the length
      of time required to achieve a dry wound and the length of stay in the hospital.
      METHODS: One hundred and twenty primary THA patients were evaluated. Pre
      operative clinical history and physical examination revealed that 29 were
      hypertensive and 91 were normotensive. The two groups were statistically matched
      using optimal propensity score matching. The outcomes of interest were the number
      of days until a dry wound was observed and the duration of hospital stay.
      RESULTS: The average systolic blood pressures were 150.1 mmHg and 120.3 mmHg for
      the hypertensive and normotensive groups, respectively. The mean number of days
      until the wound was dry was 3.79 for the hypertensive group and 2.03 for the
      normotensive group. Hypertensive patients required more days for their wounds to
      dry than normotensive patients (odds ratio  =  1.65, p<0.05). No significant
      difference in the duration of hospital stay was found between the two groups.
      CONCLUSIONS: Hypertensive patients had a higher risk of prolonged wound discharge
      after THA than their normotensive counterparts. Patients with prolonged wound
      drainage are at greater risk for infection. Clinicians should pay particular
      attention to infection-prevention strategies in hypertensive THA patients.

PMID- 21853092
TI  - EGF receptor exposed to oxidative stress acquires abnormal phosphorylation and
      aberrant activated conformation that impairs canonical dimerization.
AB  - Crystallographic studies have offered understanding of how receptor tyrosine
      kinases from the ErbB family are regulated by their growth factor ligands. A
      conformational change of the EGFR (ErbB1) was shown to occur upon ligand binding,
      where a solely ligand-mediated mode of dimerization/activation was documented.
      However, this dogma of dimerization/activation was revolutionized by the
      discovery of constitutively active ligand-independent EGFR mutants. In addition,
      other ligand-independent activation mechanisms may occur. We have shown that
      oxidative stress (ox-stress), induced by hydrogen peroxide or cigarette smoke,
      activates EGFR differently than its ligand, EGF, thereby inducing aberrant
      phosphorylation and impaired trafficking and degradation of EGFR. Here we
      demonstrate that ox-stress activation of EGFR is ligand-independent, does not
      induce "classical" receptor dimerization and is not inhibited by the tyrosine
      kinase inhibitor AG1478. Thus, an unprecedented, apparently activated, state is
      found for EGFR under ox-stress. Furthermore, this activation mechanism is
      temperature-dependent, suggesting the simultaneous involvement of membrane
      structure. We propose that ceramide increase under ox-stress disrupts cholesterol
      enriched rafts leading to EGFR re-localization into the rigid, ceramide-enriched
      rafts. This increase in ceramide also supports EGFR aberrant trafficking to a
      peri-nuclear region. Therefore, the EGFR unprecedented and activated conformation
      could be sustained by simultaneous alterations in membrane structure under ox
      stress.

PMID- 21853093
TI  - VAPA, an innovative "virus-acquisition phenotyping assay" opens new horizons in
      research into the vector-transmission of plant viruses.
AB  - Host-to-host transmission--a key step in plant virus infection cycles--is ensured
      predominantly by vectors, especially aphids and related insects. A deeper
      understanding of the mechanisms of virus acquisition, which is critical to vector
      transmission, might help to design future virus control strategies, because any
      newly discovered molecular or cellular process is a potential target for
      hampering viral spread within host populations. With this aim in mind, an aphid
      membrane-feeding assay was developed where aphids transmitted two non-circulative
      viruses [cauliflower mosaic virus (CaMV) and turnip mosaic virus] from infected
      protoplasts. In this assay, virus acquisition occurs exclusively from living
      cells. Most interestingly, we also show that CaMV is less efficiently transmitted
      by aphids in the presence of oryzalin--a microtubule-depolymerising drug. The
      example presented here demonstrates that our technically simple "virus
      acquisition phenotyping assay" (VAPA) provides a first opportunity to implement
      correlative studies relating the physiological state of infected plant cells to
      vector-transmission efficiency.

PMID- 21853094
TI  - In vivo elimination of MHC-I-deficient lymphocytes by activated natural killer
      cells is independent of granzymes A and B.
AB  - NK cells kill target cells mainly via exocytosis of granules containing perforin
      (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol
      results in apoptosis, and induction of apoptosis is severely impaired in the
      absence of gzm A and B. However, their importance for in vivo cytotoxicity by
      cytotoxic T cells has been questioned. We used an in vivo NK cytotoxicity assay,
      in which splenocytes from wild-type and beta(2)microglobulin-deficient (MHC
      I(neg)) mice are co-injected into recipients whose NK cells were activated by
      virus infection or synthetic Toll-like receptor ligands. Elimination of
      adoptively transferred MHC-I(neg) splenocytes was unimpaired in the absence of
      gzmA and gzmB, but dependent on perforin. This target cell rejection was NK cell
      dependent, since NK cell depletion abrogated it. Furthermore, target cell
      elimination in vivo was equally rapid in both wild-type and gzmAxB-deficient
      recipients, with the majority of specific target cells lost from lymphoid tissue
      within less than one to two hours after transfer. Thus, similar to T cell
      cytotoxicity, the contribution of gzmA and B to in vivo target cell elimination
      remains unresolved.

PMID- 21853095
TI  - BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats.
AB  - Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders
      that are primarily represented by ulcerative colitis and Crohn's disease. The
      etiology of IBD is not well understood; however, oxidative stress is considered a
      potential etiological and/or triggering factor for IBD. We have recently reported
      the identification of BTZO-1, an activator of antioxidant response element (ARE)
      mediated gene expression, which protects cardiomyocytes from oxidative stress
      induced insults. Here we describe the potential of BTZO-15, an active BTZO-1
      derivative for ARE-activation with a favorable ADME-Tox profile, for the
      treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1), an ARE
      regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18
      cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal
      bleeding, and an increase in rectal myeloperoxidase (MPO) activity were observed
      in a dextran sulfate sodium (DSS)-induced colitis rat model. Oral administration
      of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced
      changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity
      in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats without
      affecting rectal TNF-alpha levels. These results suggest that BTZO-15 is a
      promising compound for a novel IBD therapeutic drug with ARE activation
      properties.

PMID- 21853096
TI  - Host-size mediated trade-off in a parasitoid Sclerodermus harmandi.
AB  - Optimality models of host-parasitoid relationships have traditionally assumed
      that host quality increases as a function of host size at parasitism. However,
      trade-offs may play a crucial role in species evolution and should be found in
      host-parasitoid interactions where the host quality may differ between different
      sizes. Here, we investigated the effects of host size differences of Monochamus
      alternatus larva on foraging decisions, parasitism and related fitness in a
      gregarious ectoparasitoid, Sclerodermus harmandi. Two-choice and non-choice
      experiments were conducted with M. alternatus larvae to evaluate preference and
      performance of S. harmandi, respectively. Results from two-choice test showed
      that adult females prefer to attack large larvae rather than small larvae. In no
      choice tests, adult females needed more time to paralyze large larvae than small
      larvae before laying eggs on the body surface of M. alternatus larvae and had
      lower survival and parasitism rate on those large larvae. Foraging decisions of
      S. harmandi led to the selection of the most profitable host size for parasitoid
      development, which showed more offspring gained on large M. alternatus larvae
      than on small larvae and got higher body weight on those large hosts. This study
      demonstrates the existence of trade-off occurring during host-parasitoids
      interactions according to host size related quality.

PMID- 21853097
TI  - Expression and genetic loss of function analysis of the HAT/DESC cluster
      proteases TMPRSS11A and HAT.
AB  - Genome mining at the turn of the millennium uncovered a new family of type II
      transmembrane serine proteases (TTSPs) that comprises 17 members in humans and 19
      in mice. TTSPs phylogenetically belong to one of four subfamilies: matriptase,
      hepsin/TMPRSS, corin and HAT/DESC. Whereas a wealth of information now has been
      gathered as to the physiological functions of members of the hepsin/TMPRSS,
      matriptase, and corin subfamilies of TTSPs, comparatively little is known about
      the functions of the HAT/DESC subfamily of proteases. Here we perform a combined
      expression and functional analysis of this TTSP subfamily. We show that the five
      human and seven murine HAT/DESC proteases are coordinately expressed, suggesting
      a level of functional redundancy. We also perform a comprehensive phenotypic
      analysis of mice deficient in two of the most widely expressed HAT/DESC
      proteases, TMPRSS11A and HAT, and show that the two proteases are dispensable for
      development, health, and long-term survival in the absence of external challenges
      or additional genetic deficits. Our comprehensive expression analysis and
      generation of TMPRSS11A- and HAT-deficient mutant mouse strains provide a
      valuable resource for the scientific community for further exploration of the
      HAT/DESC subfamily proteases in physiological and pathological processes.

PMID- 21853098
TI  - Recruitment of occipital cortex during sensory substitution training linked to
      subjective experience of seeing in people with blindness.
AB  - Over three months of intensive training with a tactile stimulation device, 18
      blind and 10 blindfolded seeing subjects improved in their ability to identify
      geometric figures by touch. Seven blind subjects spontaneously reported 'visual
      qualia', the subjective sensation of seeing flashes of light congruent with
      tactile stimuli. In the latter subjects tactile stimulation evoked activation of
      occipital cortex on electroencephalography (EEG). None of the blind subjects who
      failed to experience visual qualia, despite identical tactile stimulation
      training, showed EEG recruitment of occipital cortex. None of the blindfolded
      seeing humans reported visual-like sensations during tactile stimulation. These
      findings support the notion that the conscious experience of seeing is linked to
      the activation of occipital brain regions in people with blindness. Moreover, the
      findings indicate that provision of visual information can be achieved through
      non-visual sensory modalities which may help to minimize the disability of blind
      individuals, affording them some degree of object recognition and navigation aid.

PMID- 21853099
TI  - Vitamin A supplementation at birth might prime the response to subsequent vitamin
      A supplements in girls. Three year follow-up of a randomized trial.
AB  - OBJECTIVES: Within a randomised trial of neonatal vitamin A supplementation (VAS)
      in Guinea-Bissau, neonatal VAS did not affect overall infant mortality. We
      conducted a post-hoc analysis to test the hypothesis that neonatal VAS primes the
      response to subsequent vitamin A. METHODS: All trial children were offered VAS
      after follow-up ended at 1 year of age (FU-VAS). We compared mortality between 1
      and 3 years of age according to initial randomization to neonatal VAS or placebo
      in Cox-regression models; we expected that children randomized to neonatal VAS
      compared with those randomized to placebo would have lower mortality after
      reception of FU-VAS. RESULTS: Of 4345 infants enrolled in the original trial,
      3646 lived in the study area at 1 year of age and 2958 received FU-VAS. Between 1
      and 3 years of age, 112 children died. After FU-VAS, neonatal VAS was associated
      with lower mortality than placebo: Mortality Rate Ratio (MRR) = 0.54 (95%CI: 0.31
      0.94). The effect was more pronounced in girls (MRR = 0.37 (0.16-0.89)) than boys
      (MRR = 0.73 (0.35-1.51)). The beneficial effect of neonatal VAS may have been
      particularly strong for girls who received both VAS in a campaign and FU-VAS (MRR
      = 0.15 (0.03-0.67)). Among children who had not received FU-VAS, mortality in the
      second and third year of life did not differ according to reception of neonatal
      VAS or placebo. Hence, in the second and third year of life the effect of
      neonatal VAS versus placebo was different in girls who had or had not received FU
      VAS (p for homogeneity = 0.01). CONCLUSIONS: The present results suggest that
      neonatal VAS primes the response in girls such that they get a beneficial effect
      after a subsequent dose of VAS. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00168597.

PMID- 21853100
TI  - Herceptin conjugates linked by EDC boost direct tumor cell death via programmed
      tumor cell necrosis.
AB  - Tumor-targeted antibody therapy is one of the safest biological therapeutics for
      cancer patients, but it is often ineffective at inducing direct tumor cell death
      and is ineffective against resistant tumor cells. Currently, the antitumor
      efficacy of antibody therapy is primarily achieved by inducing indirect tumor
      cell death, such as antibody-dependent cell cytotoxicity. Our study reveals that
      Herceptin conjugates, if generated via the crosslinker EDC (1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide hydrochloride), are capable of engendering
      human epidermal growth factor receptor 2 (Her2) positive tumor cells death. Using
      a high-performance liquid chromatography (HPLC) system, three peaks with
      estimated molecular weights of antibody monomer, dimer, and trimer were isolated.
      Both Herceptin trimer and dimer separated by HPLC induced significant levels of
      necrotic tumor cell death, although the trimer was more effective than the dimer.
      Notably, the Herceptin trimer also induced Herceptin-resistant tumor cell death.
      Surprisingly different from the known cell death mechanism that often results
      from antibody treatment, the Herceptin trimer elicited effective and direct tumor
      cell death via a novel mechanism: programmed cell necrosis. In Her2-positive
      cells, inhibition of necrosis pathways significantly reversed Herceptin trimer
      induced cell death. In summary, the Herceptin trimer reported herein harbors
      great potential for overcoming tumor cell resistance to Herceptin treatment.

PMID- 21853101
TI  - hSulf-1 gene exhibits anticancer efficacy through negatively regulating VEGFR-2
      signaling in human cancers.
AB  - BACKGROUND: Human sulfatase 1 (hSulf-1) is a heparin-degrading endosulfatase that
      desulfates cell surface heparan sulfate proteoglycans (HSPGs) in extracellular
      matrix and negatively modulates heparin-binding growth factor and cytokine
      signaling in cell proliferation. But hSulf-1 function is more complicated, and
      its molecular mechanism has not been well known. PRINCIPAL FINDINGS: To further
      investigate the functions of hSulf-1 gene in regulating the vascular endothelial
      growth factor receptor (VEGFR) signaling, a series of vectors expressing hSulf-1,
      hSulf-1 small hairpin RNA (shRNA) and VEGFR-2 shRNA were generated. hSulf-1 re
      expression could downregualte the VEGFR-2 phosphorylation and inhibit cancer cell
      proliferation both in ovarian and hepatocellular cancer cell lines. Knockdown of
      hSulf-1 expression by hSulf-1 shRNA enhanced the recovery of high levels of
      phosphorylated VEGFR-2, and knockdown of VEGFR-2 expression by VEGFR-2 shRNA
      inhibited the proliferation activity of cancer cells in vitro to some extent. In
      human cancer xenografts in nude mice, tumor growth was inhibited markedly after
      injections of adenovirus expressing hSulf-1, with the tumor inhibition rates of
      46.19% and 49.56% in ovarian and hepatocellular tumor models, respectively. hSulf
      1 expression significantly reduced tumor microvessel density. CONCLUSIONS: The
      results demonstrated that hSulf-1 re-expression both in ovarian and
      hepatocellular cancer cells induces antitumor efficacy by attenuating the
      phosphorylation of VEGFR-2 and suppressing angiogenesis. Therefore, hSulf-1
      mediated antiproliferation and antiangiogenesis could be a reasonable approach
      for cancer therapy.

PMID- 21853102
TI  - Evaluating experimental bias and completeness in comparative phosphoproteomics
      analysis.
AB  - Unraveling the functional dynamics of phosphorylation networks is a crucial step
      in understanding the way in which biological networks form a living cell.
      Recently there has been an enormous increase in the number of measured
      phosphorylation events. Nevertheless, comparative and integrative analysis of
      phosphoproteomes is confounded by incomplete coverage and biases introduced by
      different experimental workflows. As a result, we cannot differentiate whether
      phosphosites indentified in only one or two samples are the result of condition
      or species specific phosphorylation, or reflect missing data. Here, we evaluate
      the impact of incomplete phosphoproteomics datasets on comparative analysis, and
      we present bioinformatics strategies to quantify the impact of different
      experimental workflows on measured phosphoproteomes. We show that plotting the
      saturation in observed phosphosites in replicates provides a reproducible picture
      of the extent of a particular phosphoproteome. Still, we are still far away from
      a complete picture of the total human phosphoproteome. The impact of different
      experimental techniques on the similarity between phosphoproteomes can be
      estimated by comparing datasets from different experimental pipelines to a common
      reference. Our results show that comparative analysis is most powerful when
      datasets have been generated using the same experimental workflow. We show this
      experimentally by measuring the tyrosine phosphoproteome from Caenorhabditis
      elegans and comparing it to the tyrosine phosphoproteome of HeLa cells, resulting
      in an overlap of about 4%. This overlap between very different organisms
      represents a three-fold increase when compared to dataset of older studies,
      wherein different workflows were used. The strategies we suggest enable an
      estimation of the impact of differences in experimental workflows on the overlap
      between datasets. This will allow us to perform comparative analyses not only on
      datasets specifically generated for this purpose, but also to extract insights
      through comparative analysis of the ever-increasing wealth of publically
      available phosphorylation data.

PMID- 21853103
TI  - Predictive mapping of human risk for West Nile virus (WNV) based on environmental
      and socioeconomic factors.
AB  - A West Nile virus (WNV) human risk map was developed for Suffolk County, New York
      utilizing a case-control approach to explore the association between the risk of
      vector-borne WNV and habitat, landscape, virus activity, and socioeconomic
      variables derived from publically available datasets. Results of logistic
      regression modeling for the time period between 2000 and 2004 revealed that
      higher proportion of population with college education, increased habitat
      fragmentation, and proximity to WNV positive mosquito pools were strongly
      associated with WNV human risk. Similar to previous investigations from north
      central US, this study identified middle class suburban neighborhoods as the
      areas with the highest WNV human risk. These results contrast with similar
      studies from the southern and western US, where the highest WNV risk was
      associated with low income areas. This discrepancy may be due to regional
      differences in vector ecology, urban environment, or human behavior. Geographic
      Information Systems (GIS) analytical tools were used to integrate the risk
      factors in the 2000-2004 logistic regression model generating WNV human risk map.
      In 2005-2010, 41 out of 46 (89%) of WNV human cases occurred either inside of (30
      cases) or in close proximity (11 cases) to the WNV high risk areas predicted by
      the 2000-2004 model. The novel approach employed by this study may be implemented
      by other municipal, local, or state public health agencies to improve geographic
      risk estimates for vector-borne diseases based on a small number of acute human
      cases.

PMID- 21853104
TI  - A novel approach for mining polymorphic microsatellite markers in silico.
AB  - An important emerging application of high-throughput 454 sequencing is the
      isolation of molecular markers such as microsatellites from genomic DNA. However,
      few studies have developed microsatellites from cDNA despite the added potential
      for targeting candidate genes. Moreover, to develop microsatellites usually
      requires the evaluation of numerous primer pairs for polymorphism in the focal
      species. This can be time-consuming and wasteful, particularly for taxa with low
      genetic diversity where the majority of primers often yield monomorphic
      polymerase chain reaction (PCR) products. Transcriptome assemblies provide a
      convenient solution, functional annotation of transcripts allowing markers to be
      targeted towards candidate genes, while high sequence coverage in principle
      permits the assessment of variability in silico. Consequently, we evaluated fifty
      primer pairs designed to amplify microsatellites, primarily residing within
      transcripts related to immunity and growth, identified from an Antarctic fur seal
      (Arctocephalus gazella) transcriptome assembly. In silico visualization was used
      to classify each microsatellite as being either polymorphic or monomorphic and to
      quantify the number of distinct length variants, each taken to represent a
      different allele. The majority of loci (n = 36, 76.0%) yielded interpretable PCR
      products, 23 of which were polymorphic in a sample of 24 fur seal individuals.
      Loci that appeared variable in silico were significantly more likely to yield
      polymorphic PCR products, even after controlling for microsatellite length
      measured in silico. We also found a significant positive relationship between
      inferred and observed allele number. This study not only demonstrates the
      feasibility of generating modest panels of microsatellites targeted towards
      specific classes of gene, but also suggests that in silico microsatellite
      variability may provide a useful proxy for PCR product polymorphism.

PMID- 21853105
TI  - Testosterone, plumage colouration and extra-pair paternity in male North-American
      barn swallows.
AB  - In most monogamous bird species, circulating testosterone concentration in males
      is elevated around the social female's fertile period. Variation in elevated
      testosterone concentrations among males may have a considerable impact on
      fitness. For example, testosterone implants enhance behaviours important for
      social and extra-pair mate choice. However, little is known about the
      relationship between natural male testosterone concentration and sexual
      selection. To investigate this relationship we measured testosterone
      concentration and sexual signals (ventral plumage colour and tail length), and
      determined within and extra-pair fertilization success in male North American
      barn swallows (Hirundo rustica erythrogaster). Dark rusty coloured males had
      higher testosterone concentrations than drab males. Extra-pair paternity was
      common (42% and 31% of young in 2009 and 2010, respectively), but neither within-
      nor extra-pair fertilization success was related to male testosterone
      concentration. Dark rusty males were less often cuckolded, but did not have
      higher extra-pair or total fertilization success than drab males. Tail length did
      not affect within- or extra-pair fertilization success. Our findings suggest
      that, in North American barn swallows, male testosterone concentration does not
      play a significant direct role in female mate choice and sexual selection.
      Possibly plumage colour co-varies with a male behavioural trait, such as
      aggressiveness, that reduces the chance of cuckoldry. This could also explain why
      dark males have higher testosterone concentrations than drab males.

PMID- 21853106
TI  - Clinical, biological and genetic analysis of anorchia in 26 boys.
AB  - BACKGROUND: Anorchia is defined as the absence of testes in a 46,XY individual
      with a male phenotype. The cause is unknown. METHODS: We evaluated the clinical
      and biological presentation, and family histories of 26 boys with anorchia, and
      sequenced their SRY, NR5A1, INSL3, MAMLD1 genes and the T222P variant for LGR8.
      RESULTS: No patient had any associated congenital anomaly. At birth, testes were
      palpable bilaterally or unilaterally in 13 cases and not in 7; one patient
      presented with bilateral testicular torsion immediately after birth. The basal
      plasma concentrations of anti-Mullerian hormone (AMH, n = 15), inhibin B (n = 7)
      and testosterone (n = 19) were very low or undetectable in all the patients
      evaluated, as were the increases in testosterone after human chorionic
      gonadotropin (hCG, n = 12). The basal plasma concentrations of follicle
      stimulating hormone (FSH) were increased in 20/25, as was that of luteinising
      hormone in 10/22 cases. Family members of 7/26 cases had histories of primary
      ovarian failure in the mother (n = 2), or sister 46,XX, together with fetal
      malformations of the only boy with microphallus and secondary foot edema (n = 1),
      secondary infertility in the father (n = 2), or cryptorchidism in first cousins
      (n = 2). The sequences of all the genes studied were normal. CONCLUSION:
      Undetectable plasma concentrations of AMH and inhibin B and an elevated plasma
      FSH, together with 46,XY complement are sufficient for diagnosis of anorchia. The
      hCG test is unnecessary. NR5A1 and other genes implicated in gonadal development
      and testicle descent were not mutated, which suggests that other genes involved
      in these developments contribute to the phenotypes.

PMID- 21853107
TI  - Association between walking speed and age in healthy, free-living individuals
      using mobile accelerometry--a cross-sectional study.
AB  - CONTEXT: Walking speed is a fundamental parameter of human motion and is
      increasingly considered as an important indicator of individuals' health status.
      OBJECTIVE: To evaluate the relationship of gait parameters, and demographic and
      physical characteristics in healthy men and women. DESIGN, SETTING, AND
      PARTICIPANTS: Recruitment of a subsample (n = 358) of male and female blood
      donors taking part in the Cambridge CardioResource study. Collection of
      demographic data, measurement of physical characteristics (height, weight and
      blood pressure) and assessment of 7-day, free-living activity parameters using
      accelerometry and a novel algorithm to measure walking speed. Participants were a
      median (interquartile range[IQR]) age of 49 (16) years; 45% women; and had a
      median (IQR) BMI of 26 (5.4). MAIN OUTCOME MEASURE: Walking speed. RESULTS: In
      this study, the hypothesis that walking speed declines with age was generated
      using an initial 'open' dataset. This was subsequently validated in a separate
      'closed' dataset that showed a decrease of walking speed of -0.0037 m/s per year.
      This is equivalent to a difference of 1.2 minutes, when walking a distance of 1
      km aged 20 compared to 60 years. Associations between walking speed and other
      participant characteristics (i.e. gender, BMI and blood pressure) were non
      significant. BMI was negatively correlated with the number of walking and running
      steps and longest non-stop distance. CONCLUSION: This is the first study using
      accelerometry which shows an association between walking speed and age in free
      living, healthy individuals. Absolute values of gait speed are comparable to
      published normal ranges in clinical settings. This study highlights the potential
      use of mobile accelerometry to assess gait parameters which may be indicative of
      future health outcomes in healthy individuals.

PMID- 21853108
TI  - Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over Rev
      peptide is mainly enthalpic in origin.
AB  - Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive
      element (RRE) present within the env gene of HIV-1 RNA genome. This binding
      facilitates the transport of the RNA to the cytoplasm, which in turn triggers the
      switch between viral latency and active viral replication. Essential components
      of this complex have been localized to a minimal arginine rich Rev peptide and
      stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high
      binding affinity and specificity to the RRE-IIB than the Rev peptide, however the
      thermodynamic basis of this specificity has not yet been addressed. The present
      study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over
      Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG
      1.2 binding stabilizes the RRE structure significantly (DeltaT(m) = 4.3 degrees
      C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the
      binding have also been found to be different for both the peptides. At pH 7.5,
      RSG-1.2 binds RRE-IIB with a K(a) = 16.2+/-0.6*10(7) M(-1) where enthalpic change
      DeltaH = -13.9+/-0.1 kcal/mol is the main driving force with limited unfavorable
      contribution from entropic change TDeltaS = -2.8+/-0.1 kcal/mol. A large part of
      DeltaH may be due to specific stacking between U72 and Arg15. In contrast binding
      of Rev (K(a) = 3.1+/-0.4*10(7) M(-1)) is driven mainly by entropy (DeltaH = 0
      kcal/mol and TDeltaS = 10.2+/-0.2 kcal/mol) which arises from major
      conformational changes in the RNA upon binding.

PMID- 21853109
TI  - Frequent alteration of MLL3 frameshift mutations in microsatellite deficient
      colorectal cancer.
AB  - BACKGROUND: MLL3 is a histone 3-lysine 4 methyltransferase with tumor-suppressor
      properties that belongs to a family of chromatin regulator genes potentially
      altered in neoplasia. Mutations in MLL3 were found in a whole genome analysis of
      colorectal cancer but have not been confirmed by a separate study. METHODS AND
      RESULTS: We analyzed mutations of coding region and promoter methylation in MLL3
      using 126 cases of colorectal cancer. We found two isoforms of MLL3 and DNA
      sequencing revealed frameshift and other mutations affecting both isoforms of
      MLL3 in colorectal cancer cells and 19 of 134 (14%) primary colorectal samples
      analyzed. Moreover, frameshift mutations were more common in cases with
      microsatellite instability (31%) both in CRC cell lines and primary tumors. The
      largest isoform of MLL3 is transcribed from a CpG island-associated promoter that
      has highly homology with a pseudo-gene on chromosome 22 (psiTPTE22). Using an
      assay which measured both loci simultaneously we found prominent age related
      methylation in normal colon (from 21% in individuals less than 25 years old to
      56% in individuals older than 70, R = 0.88, p<0.001) and frequent
      hypermethylation (83%) in both CRC cell lines and primary tumors. We next studied
      the two loci separately and found that age and cancer related methylation was
      solely a property of the pseudogene CpG island and that the MLL3 loci was
      unmethylated. CONCLUSIONS: We found that frameshift mutations of MLL3 in both CRC
      cells and primary tumor that were more common in cases with microsatellite
      instability. Moreover, we have shown CpG island-associated promoter of MLL3 gene
      has no DNA methylation in CRC cells but also primary tumor and normal colon, and
      this region has a highly homologous of pseudo gene (psiTPTE22) that was age
      relate DNA methylation.

PMID- 21853110
TI  - Snail involves in the transforming growth factor beta1-mediated epithelial
      mesenchymal transition of retinal pigment epithelial cells.
AB  - BACKGROUND: The proliferation of retinal pigment epithelium (RPE) cells resulting
      from an epithelial-mesenchymal transition (EMT) plays a key role in proliferative
      vitreoretinopathy (PVR), which leads to complex retinal detachment and the loss
      of vision. Genes of Snail family encode the zinc finger transcription factors
      that have been reported to be essential in EMT during embryonic development and
      cancer metastasis. However, the function of Snail in RPE cells undergoing EMT is
      largely unknown. PRINCIPAL FINDINGS: Transforming growth factor beta(TGF-beta)-1
      resulted in EMT in human RPE cells (ARPE-19), which was characterized by the
      expected decrease in E-cadherin and Zona occludin-1(ZO-1) expression, and the
      increase in fibronectin and alpha-smooth muscle actin (alpha-SMA) expression, as
      well as the associated increase of Snail expression at both mRNA and protein
      levels. Furthermore, TGF-beta1 treatment caused a significant change in ARPE-19
      cells morphology, with transition from a typical epithelial morphology to
      mesenchymal spindle-shaped. More interestingly, Snail silencing significantly
      attenuated TGF-beta1-induced EMT in ARPE-19 cells by decreasing the mesenchymal
      markers fibronectin and a-SMA and increasing the epithelial marker E-cadherin and
      ZO-1. Snail knockdown could effectively suppress ARPE-19 cell migration. Finally,
      Snail was activated in epiretinal membranes from PVR patients. Taken together,
      Snail plays very important roles in TGF-beta-1-induced EMT in human RPE cells and
      may contribute to the development of PVR. SIGNIFICANCE: Snail transcription
      factor plays a critical role in TGF-beta1-induced EMT in human RPE cells, which
      provides deep insight into the pathogenesis of human PVR disease. The specific
      inhibition of Snail may provide a new approach to treat and prevent PVR.

PMID- 21853111
TI  - A novel halophilic lipase, LipBL, showing high efficiency in the production of
      eicosapentaenoic acid (EPA).
AB  - BACKGROUND: Among extremophiles, halophiles are defined as microorganisms adapted
      to live and thrive in diverse extreme saline environments. These extremophilic
      microorganisms constitute the source of a number of hydrolases with great
      biotechnological applications. The interest to use extremozymes from halophiles
      in industrial applications is their resistance to organic solvents and extreme
      temperatures. Marinobacter lipolyticus SM19 is a moderately halophilic bacterium,
      isolated previously from a saline habitat in South Spain, showing lipolytic
      activity. METHODS AND FINDINGS: A lipolytic enzyme from the halophilic bacterium
      Marinobacter lipolyticus SM19 was isolated. This enzyme, designated LipBL, was
      expressed in Escherichia coli. LipBL is a protein of 404 amino acids with a
      molecular mass of 45.3 kDa and high identity to class C beta-lactamases. LipBL
      was purified and biochemically characterized. The temperature for its maximal
      activity was 80 degrees C and the pH optimum determined at 25 degrees C was 7.0,
      showing optimal activity without sodium chloride, while maintaining 20% activity
      in a wide range of NaCl concentrations. This enzyme exhibited high activity
      against short-medium length acyl chain substrates, although it also hydrolyzes
      olive oil and fish oil. The fish oil hydrolysis using LipBL results in an
      enrichment of free eicosapentaenoic acid (EPA), but not docosahexaenoic acid
      (DHA), relative to its levels present in fish oil. For improving the stability
      and to be used in industrial processes LipBL was immobilized in different
      supports. The immobilized derivatives CNBr-activated Sepharose were highly
      selective towards the release of EPA versus DHA. The enzyme is also active
      towards different chiral and prochiral esters. Exposure of LipBL to buffer
      solvent mixtures showed that the enzyme had remarkable activity and stability in
      all organic solvents tested. CONCLUSIONS: In this study we isolated, purified,
      biochemically characterized and immobilized a lipolytic enzyme from a halophilic
      bacterium M. lipolyticus, which constitutes an enzyme with excellent properties
      to be used in the food industry, in the enrichment in omega-3 PUFAs.

PMID- 21853112
TI  - Quantitative resistance of potato to Pectobacterium atrosepticum and Phytophthora
      infestans: integrating PAMP-triggered response and pathogen growth.
AB  - While the mechanisms underlying quantitative resistance of plants to pathogens
      are still not fully elucidated, the Pathogen-Associated Molecular Patterns
      (PAMPs)-triggered response model suggests that such resistance depends on a
      dynamic interplay between the plant and the pathogen. In this model, the
      pathogens themselves or elicitors they produce would induce general defense
      pathways, which in turn limit pathogen growth and host colonisation. It therefore
      suggests that quantitative resistance is directly linked to a common set of
      general host defense mechanisms, but experimental evidence is still inconclusive.
      We tested the PAMP-triggered model using two pathogens (Pectobacterium
      atrosepticum and Phytophthora infestans) differing by their infectious processes
      and five potato cultivars spanning a range of resistance levels to each pathogen.
      Phenylalanine ammonia-lyase (PAL) activity, used as a defense marker, and
      accumulation of phenolics were measured in tuber slices challenged with
      lipopolysaccharides from P. atrosepticum or a concentrated culture filtrate from
      P. infestans. PAL activity increased following treatment with the filtrate but
      not with lipopolysaccharides, and varied among cultivars. It was positively
      related to tuber resistance to P. atrosepticum, but negatively related to tuber
      resistance to P. infestans. It was also positively related to the accumulation of
      total phenolics. Chlorogenic acid, the main phenolic accumulated, inhibited
      growth of both pathogens in vitro, showing that PAL induction caused active
      defense against each of them. Tuber slices in which PAL activity had been induced
      before inoculation showed increased resistance to P. atrosepticum, but not to P.
      infestans. Our results show that inducing a general defense mechanism does not
      necessarily result in quantitative resistance. As such, they invalidate the
      hypothesis that the PAMP-triggered model alone can explain quantitative
      resistance. We thus designed a more complex model integrating physiological host
      response and a key pathogen life history trait, pathogen growth, to explain the
      differences between the two pathosystems.

PMID- 21853113
TI  - Revealing natural relationships among arbuscular mycorrhizal fungi: culture line
      BEG47 represents Diversispora epigaea, not Glomus versiforme.
AB  - BACKGROUND: Understanding the mechanisms underlying biological phenomena, such as
      evolutionarily conservative trait inheritance, is predicated on knowledge of the
      natural relationships among organisms. However, despite their enormous ecological
      significance, many of the ubiquitous soil inhabiting and plant symbiotic
      arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota) are incorrectly
      classified. METHODOLOGY/PRINCIPAL FINDINGS: Here, we focused on a frequently used
      model AMF registered as culture BEG47. This fungus is a descendent of the ex-type
      culture-lineage of Glomus epigaeum, which in 1983 was synonymised with Glomus
      versiforme. It has since then been used as 'G. versiforme BEG47'. We show by
      morphological comparisons, based on type material, collected 1860-61, of G.
      versiforme and on type material and living ex-type cultures of G. epigaeum, that
      these two AMF species cannot be conspecific, and by molecular phylogenetics that
      BEG47 is a member of the genus Diversispora. CONCLUSIONS: This study highlights
      that experimental works published during the last >25 years on an AMF named 'G.
      versiforme' or 'BEG47' refer to D. epigaea, a species that is actually
      evolutionarily separated by hundreds of millions of years from all members of the
      genera in the Glomerales and thus from most other commonly used AMF 'laboratory
      strains'. Detailed redescriptions substantiate the renaming of G. epigaeum
      (BEG47) as D. epigaea, positioning it systematically in the order
      Diversisporales, thus enabling an evolutionary understanding of genetical,
      physiological, and ecological traits, relative to those of other AMF.
      Diversispora epigaea is widely cultured as a laboratory strain of AMF, whereas G.
      versiforme appears not to have been cultured nor found in the field since its
      original description.

PMID- 21853114
TI  - Withaferin A-induced apoptosis in human breast cancer cells is mediated by
      reactive oxygen species.
AB  - Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal
      plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast
      cancer cells in culture and MDA-MB-231 xenografts in vivo in association with
      apoptosis induction, but the mechanism of cell death is not fully understood. We
      now demonstrate, for the first time, that WA-induced apoptosis is mediated by
      reactive oxygen species (ROS) production due to inhibition of mitochondrial
      respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells,
      but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also
      resistant to WA-induced apoptosis. WA-mediated ROS production as well as
      apoptotic histone-associated DNA fragment release into the cytosol was
      significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in
      both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was
      accompanied by inhibition of oxidative phosphorylation and inhibition of complex
      III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7
      cells were resistant to WA-induced ROS production, collapse of mitochondrial
      membrane potential, and apoptosis compared with respective wild-type cells. WA
      treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells,
      and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double
      knockout mouse were significantly more resistant to WA-induced apoptosis compared
      with fibroblasts derived from wild-type mouse. In conclusion, the present study
      provides novel insight into the molecular circuitry of WA-induced apoptosis
      involving ROS production and activation of Bax/Bak.

PMID- 21853115
TI  - Empathy and reversed empathy of stress in mice.
AB  - Empathy is an emotional response to display of distress in others and reversed
      empathy is an emotional response to non-distressed others in distressed subjects.
      Stress has memory enhancing effect on aversive experience. Here, I examine
      empathy and reversed empathy using the memory enhancing effects of stress in
      mice. Restrain stress enhanced aversive memory of a floor with electric shock,
      but restrain stress, with cage mates also restrained, reduced the enhancing
      effect. On the other hand, restrain stress with free-moving cage mates increased
      the memory enhancing effect, suggesting the stronger stress. This is the reversed
      empathy. Level of corticosterone is the highest after the restrain with free
      moving mates and lowest after the restrain with restrained mates.

PMID- 21853116
TI  - Conventional and novel Ggamma protein families constitute the heterotrimeric G
      protein signaling network in soybean.
AB  - Heterotrimeric G-proteins comprised of Galpha, Gbeta and Ggamma proteins are
      important signal transducers in all eukaryotes. The Ggamma protein of the G
      protein heterotrimer is crucial for its proper targeting at the plasma membrane
      and correct functioning. Ggamma proteins are significantly smaller and more
      diverse than the Galpha and Gbeta proteins. In model plants Arabidopsis and rice
      that have a single Galpha and Gbeta protein, the presence of two canonical Ggamma
      proteins provide some diversity to the possible heterotrimeric combinations. Our
      recent analysis of the latest version of the soybean genome has identified ten
      Ggamma proteins which belong to three distinct families based on their C-termini.
      We amplified the full length cDNAs, analyzed their detailed expression profile by
      quantitative PCR, assessed their localization and performed yeast-based
      interaction analysis to evaluate interaction specificity with different Gbeta
      proteins. Our results show that ten Ggamma genes are retained in the soybean
      genome and have interesting expression profiles across different developmental
      stages. Six of the newly identified proteins belong to two plant-specific Ggamma
      protein families. Yeast-based interaction analyses predict some degree of
      interaction specificity between different Gbeta and Ggamma proteins. This
      research thus identifies a highly diverse G-protein network from a plant species.
      Homologs of these novel proteins have been previously identified as QTLs for
      grain size and yield in rice.

PMID- 21853117
TI  - Contrasting effects of leptin on food anticipatory and total locomotor activity.
AB  - Obese, leptin deficient obob mice have profoundly decreased activity and
      increased food seeking behavior. The decreased activity has been attributed to
      obesity. In mice, we tested the hypothesis that leptin increases total locomotor
      activity but inhibits food anticipatory activity. We also sought to determine if
      leptin induced increases in total locomotor activity are independent of changes
      in body weight and obesity. We studied obob mice and also created a novel
      transgenic mouse where leptin is over-expressed in a tetracycline-off system and
      can be abruptly and non-invasively suppressed by doxycycline within few hours.
      The studies were performed using two independent behavioral assays: home cage
      activity (HCA) and running wheel activity (RWA). Systemic administration of
      leptin (150 ng/hr) to obob mice produced a 122%+/-30% (mean +/- SEM) increase
      (p<=0.01) in locomotor activity within 2 days In addition, cerebroventricular
      administration of leptin (5 ng/hr) also produced an early and progressive
      increase in total locomotor activity beginning on the 1st day (+28+/-8%; p<=0.05)
      and increasing to +69+/-23% on day 3 without a decrease in body weight during
      this time. The increase in activity was restricted to the dark phase. Conversely,
      in a tet-off transgenic obob mouse line, acute leptin suppression reduced
      spontaneous locomotor activity. To further define activities that are leptin
      regulated, we assayed food anticipatory activity (FAA) and found that it was
      markedly augmented in obob mice compared to wild type mice (+38+/-6.7 in obob vs
      +20+/-6.3% in wild type at peak; mean +/- SEM; p<=0.001) and abolished by leptin.
      Although melanocortin-3 receptors (MC3R) reportedly mediate FAA, we found
      augmented FAA and preserved inhibitory effects of leptin on FAA in MC3R-/-obob
      mice. In summary, this study demonstrates that total activity and FAA are
      regulated independently by leptin. Leptin, acting in the central nervous system
      and at physiologic levels, produces early increases in locomotor activity before
      substantial weight loss. In contrast, leptin suppresses augmented food
      anticipatory activity in obob mice.

PMID- 21853118
TI  - Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin
      resistance in mice: genomic analysis of cellular targets.
AB  - Patients with non-alcoholic fatty liver disease are characterised by a decreased
      n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The
      metabolic consequences of n-3 PUFA depletion in the liver are poorly understood.
      We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by
      feeding C57Bl/6J mice for 3 months with an n-3 PUFA depleted diet (DEF) versus a
      control diet (CT), which only differed in the PUFA content. DEF mice exhibited
      hepatic insulin resistance (assessed by euglycemic-hyperinsulinemic clamp) and
      steatosis that was associated with a decrease in fatty acid oxidation and
      occurred despite a higher capacity for triglyceride secretion. Microarray and
      qPCR analysis of the liver tissue revealed higher expression of all the enzymes
      involved in lipogenesis in DEF mice compared to CT mice, as well as increased
      expression and activation of sterol regulatory element binding protein-1c (SREBP
      1c). Our data suggest that the activation of the liver X receptor pathway is
      involved in the overexpression of SREBP-1c, and this phenomenon cannot be
      attributed to insulin or to endoplasmic reticulum stress responses. In
      conclusion, n-3 PUFA depletion in liver phospholipids leads to activation of
      SREBP-1c and lipogenesis, which contributes to hepatic steatosis.

PMID- 21853119
TI  - Influenza virus infection induces the nuclear relocalization of the Hsp90 co
      chaperone p23 and inhibits the glucocorticoid receptor response.
AB  - The genomic RNAs of influenza A viruses are associated with the viral polymerase
      subunits (PB1, PB2, PA) and nucleoprotein (NP), forming ribonucleoprotein
      complexes (RNPs). Transcription/replication of the viral genome occurs in the
      nucleus of infected cells. A role for Hsp90 in nuclear import and assembly of
      newly synthetized RNA-polymerase subunits has been proposed. Here we report that
      the p23 cochaperone of Hsp90, which plays a major role in glucocorticoid receptor
      folding and function, associates with influenza virus polymerase. We show that
      p23 is not essential for viral multiplication in cultured cells but relocalizes
      to the nucleus in influenza virus-infected cells, which may alter some functions
      of p23 and Hsp90. Moreover, we show that influenza virus infection inhibits
      glucocorticoid receptor-mediated gene transactivation, and that this negative
      effect can occur through a p23-independent pathway. Viral-induced inhibition of
      the glucocorticoid receptor response might be of significant importance regarding
      the physiopathology of influenza infections in vivo.

PMID- 21853120
TI  - Stimulus-specific adaptation and deviance detection in the rat auditory cortex.
AB  - Stimulus-specific adaptation (SSA) is the specific decrease in the response to a
      frequent ('standard') stimulus, which does not generalize, or generalizes only
      partially, to another, rare stimulus ('deviant'). Stimulus-specific adaptation
      could result simply from the depression of the responses to the standard.
      Alternatively, there may be an increase in the responses to the deviant stimulus
      due to the violation of expectations set by the standard, indicating the presence
      of true deviance detection. We studied SSA in the auditory cortex of halothane
      anesthetized rats, recording local field potentials and multi-unit activity. We
      tested the responses to pure tones of one frequency when embedded in sequences
      that differed from each other in the frequency and probability of the tones
      composing them. The responses to tones of the same frequency were larger when
      deviant than when standard, even with inter-stimulus time intervals of almost 2
      seconds. Thus, SSA is present and strong in rat auditory cortex. SSA was present
      even when the frequency difference between deviants and standards was as small as
      10%, substantially smaller than the typical width of cortical tuning curves,
      revealing hyper-resolution in frequency. Strong responses were evoked also by a
      rare tone presented by itself, and by rare tones presented as part of a sequence
      of many widely spaced frequencies. On the other hand, when presented within a
      sequence of narrowly spaced frequencies, the responses to a tone, even when rare,
      were smaller. A model of SSA that included only adaptation of the responses in
      narrow frequency channels predicted responses to the deviants that were
      substantially smaller than the observed ones. Thus, the response to a deviant is
      at least partially due to the change it represents relative to the regularity set
      by the standard tone, indicating the presence of true deviance detection in rat
      auditory cortex.

PMID- 21853121
TI  - Large scale replication study of the association between HLA class II/BTNL2
      variants and osteoarthritis of the knee in European-descent populations.
AB  - Osteoarthritis (OA) is the most common form of arthritis and a major cause of
      disability. This study evaluates the association in Caucasian populations of two
      single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen
      (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA
      in Japanese populations. The frequencies for rs10947262 were compared in 36,408
      controls and 5,749 knee OA cases from European-descent populations. rs7775228 was
      tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk
      (major) allele at rs10947262 in Caucasian samples was not significantly
      associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For
      rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for
      the allele associated with risk in the Japanese GWAS. In Japanese individuals
      these two SNPs are in strong linkage disequilibrium (LD) (r(2) = 0.86) with the
      HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian
      and Chinese samples, using imputed data, these SNPs appear not to be in LD with
      that haplotype (r(2)<0.07). The rs10947262 and rs7775228 variants are not
      associated with risk of knee OA in European descent populations and they do not
      appear tag the same HLA class II haplotype as they do in Japanese individuals.

PMID- 21853122
TI  - A comparison of exogenous promoter activity at the ROSA26 locus using a PhiiC31
      integrase mediated cassette exchange approach in mouse ES cells.
AB  - The activities of nine ubiquitous promoters (ROSA26, CAG, CMV, CMVd1, UbC,
      EF1alpha, PGK, chicken beta-actin and MC1) have been quantified and compared in
      mouse embryonic stem cells. To avoid the high variation in transgene expression
      which results from uncontrolled copy number and chromosomal position effects when
      using random insertion based transgenic approaches, we have adopted a PhiC31
      integrase mediated cassette exchange method for the efficient insertion of
      transgenes at single copy within a defined and well characterized chromosomal
      position, ROSA26. This has enabled the direct comparison of constructs from
      within the same genomic context and allows a systematic and quantitative
      assessment of the strengths of the promoters in comparison with the endogenous
      ROSA26 promoter. The behavior of these exogenous promoters, when integrated at
      ROSA26 in both sense and antisense orientations, reveals a large variation in
      their levels of activity. In addition, a subset of promoters, EF1alpha, UbC and
      CAG, show an increased activity in the sense orientation as a consequence of
      integration. Transient transfection experiments confirmed these observations to
      reflect integration dependent effects and also revealed significant differences
      in the behaviour of these promoters when delivered transiently or stably. As well
      as providing an important reference which will facilitate the choice of an
      appropriate promoter to achieve the desired level of expression for a specific
      research question, this study also demonstrates the suitability of the cassette
      exchange methodology for the robust and reliable expression of multiple variant
      transgenes in ES cells.

PMID- 21853123
TI  - An RNA interference phenotypic screen identifies a role for FGF signals in colon
      cancer progression.
AB  - In tumor cells, stepwise oncogenic deregulation of signaling cascades induces
      alterations of cellular morphology and promotes the acquisition of malignant
      traits. Here, we identified a set of 21 genes, including FGF9, as determinants of
      tumor cell morphology by an RNA interference phenotypic screen in SW480 colon
      cancer cells. Using a panel of small molecular inhibitors, we subsequently
      established phenotypic effects, downstream signaling cascades, and associated
      gene expression signatures of FGF receptor signals. We found that inhibition of
      FGF signals induces epithelial cell adhesion and loss of motility in colon cancer
      cells. These effects are mediated via the mitogen-activated protein kinase (MAPK)
      and Rho GTPase cascades. In agreement with these findings, inhibition of the
      MEK1/2 or JNK cascades, but not of the PI3K-AKT signaling axis also induced
      epithelial cell morphology. Finally, we found that expression of FGF9 was strong
      in a subset of advanced colon cancers, and overexpression negatively correlated
      with patients' survival. Our functional and expression analyses suggest that FGF
      receptor signals can contribute to colon cancer progression.

PMID- 21853124
TI  - Overexpression of ubiquitin specific protease 44 (USP44) induces chromosomal
      instability and is frequently observed in human T-cell leukemia.
AB  - Cdc20-anaphase promoting complex/cyclosome (Cdc20-APC/C) E3 ubiquitin ligase
      activity is essential for orderly mitotic progression. The deubiqituinase USP44
      was identified as a key regulator of APC/C and has been proposed to suppress
      Cdc20-APC/C activity by maintaining its association with the inhibitory protein
      Mad2 until all chromosomes are properly attached to the mitotic spindle. However,
      this notion has been challenged by data in which a lysine-less mutant of Cdc20
      leads to premature anaphase, suggesting that it's ubiquitination is not required
      for APC/C activation. To further evaluate its role in checkpoint function and
      chromosome instability, we studied the consequences of over-expression of mouse
      Usp44 in non-transformed murine embryonic fibroblasts. Here we show that cells
      with high Usp44 are prone to chromosome segregation errors and aneuploidization.
      We find that high Usp44 promotes association of Mad2 with Cdc20 and reinforces
      the mitotic checkpoint. Surprisingly, the APC/C-Cdc20 substrate cyclin B1 is
      stabilized in G2 when Usp44 is over-expressed, but is degraded with normal
      kinetics once cells enter mitosis. Furthermore, we show that USP44 expression is
      elevated in subset of T-cell leukemias. These data are consistent with an
      important role for USP44 in regulating Cdc20-APC/C activity and suggest that high
      levels of this enzyme may contribute to the pathogenesis of T-ALL.

PMID- 21853125
TI  - Variation, variability, and the origin of the avian endocranium: insights from
      the anatomy of Alioramus altai (Theropoda: Tyrannosauroidea).
AB  - The internal braincase anatomy of the holotype of Alioramus altai, a relatively
      small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied
      using high-resolution computed tomography. A number of derived characters
      strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new
      species (e.g., endocranial position of the gasserian ganglion, internal
      ramification of the facial nerve). Also present are features intermediate between
      the basal theropod and avialan conditions that optimize as the ancestral
      condition for Coelurosauria--a diverse group of derived theropods that includes
      modern birds. The expression of several primitive theropod features as derived
      character states within Tyrannosauroidea establishes previously unrecognized
      evolutionary complexity and morphological plasticity at the base of
      Coelurosauria. It also demonstrates the critical role heterochrony may have
      played in driving patterns of endocranial variability within the group and
      potentially reveals stages in the evolution of neuroanatomical development that
      could not be inferred based solely on developmental observations of the major
      archosaurian crown clades. We discuss the integration of paleontology with
      variability studies, especially as applied to the nature of morphological
      transformations along the phylogenetically long branches that tend to separate
      the crown clades of major vertebrate groups.

PMID- 21853126
TI  - Pancreatic neuroendocrine tumors in glucagon receptor-deficient mice.
AB  - Inhibition of glucagon signaling causes hyperglucagonemia and pancreatic alpha
      cell hyperplasia in mice. We have recently demonstrated that a patient with an
      inactivating glucagon receptor mutation (P86S) also exhibits hyperglucagonemia
      and pancreatic alpha cell hyperplasia but further develops pancreatic
      neuroendocrine tumors (PNETs). To test the hypothesis that defective glucagon
      signaling causes PNETs, we studied the pancreata of mice deficient in glucagon
      receptor (Gcgr(-/-)) from 2 to 12 months, using WT and heterozygous mice as
      controls. At 2-3 months, Gcgr(-/-) mice exhibited normal islet morphology but the
      islets were mostly composed of alpha cells. At 5-7 months, dysplastic islets were
      evident in Gcgr(-/-) mice but absent in WT or heterozygous controls. At 10-12
      months, gross PNETs (>=1 mm) were detected in most Gcgr(-/-) pancreata and micro
      PNETs (<1 mm) were found in all (n = 14), whereas the islet morphology remained
      normal and no PNETs were found in any WT (n = 10) or heterozygous (n = 25)
      pancreata. Most PNETs in Gcgr(-/-) mice were glucagonomas, but some were non
      functioning. No tumors predominantly expressed insulin, pancreatic polypeptide,
      or somatostatin, although some harbored focal aggregates of tumor cells
      expressing one of those hormones. The PNETs in Gcgr(-/-) mice were well
      differentiated and occasionally metastasized to the liver. Menin expression was
      aberrant in most dysplatic islets and PNETs. Vascular endothelial growth factor
      (VEGF) was overexpressed in PNET cells and its receptor Flk-1 was found in the
      abundant blood vessels or blood islands inside the tumors. We conclude that
      defective glucagon signaling causes PNETs in the Gcgr(-/-) mice, which may be
      used as a model of human PNETs. Our results further suggest that completely
      inhibiting glucagon signaling may not be a safe approach to treat diabetes.

PMID- 21853127
TI  - RNAi screen reveals host cell kinases specifically involved in Listeria
      monocytogenes spread from cell to cell.
AB  - Intracellular bacterial pathogens, such as Listeria monocytogenes and Rickettsia
      conorii display actin-based motility in the cytosol of infected cells and spread
      from cell to cell through the formation of membrane protrusions at the cell
      cortex. Whereas the mechanisms supporting cytosolic actin-based motility are
      fairly well understood, it is unclear whether specific host factors may be
      required for supporting the formation and resolution of membrane protrusions. To
      address this gap in knowledge, we have developed high-throughput fluorescence
      microscopy and computer-assisted image analysis procedures to quantify pathogen
      spread in human epithelial cells. We used the approach to screen a siRNA library
      covering the human kinome and identified 7 candidate kinases whose depletion led
      to severe spreading defects in cells infected with L. monocytogenes. We conducted
      systematic validation procedures with redundant silencing reagents and confirmed
      the involvement of the serine/threonine kinases, CSNK1A1 and CSNK2B. We conducted
      secondary assays showing that, in contrast with the situation observed in CSNK2B
      depleted cells, L. monocytogenes formed wild-type cytosolic tails and displayed
      wild-type actin-based motility in the cytosol of CSNK1A1-depleted cells.
      Furthermore, we developed a protrusion formation assay and showed that the
      spreading defect observed in CSNK1A1-depleted cells correlated with the formation
      of protrusion that did not resolve into double-membrane vacuoles. Moreover, we
      developed sending and receiving cell-specific RNAi procedures and showed that
      CSNK1A was required in the sending cells, but was dispensable in the receiving
      cells, for protrusion resolution. Finally, we showed that the observed defects
      were specific to Listeria monocytogenes, as Rickettsia conorii displayed wild
      type cell-to-cell spread in CSNK1A1- and CSNK2B-depleted cells. We conclude that,
      in addition to the specific host factors supporting cytosolic actin-based
      motility, such as CSNK2B, Listeria monocytogenes requires specific host factors,
      such as CSNK1A1 in order to form productive membrane protrusions and spread from
      cell to cell.

PMID- 21853128
TI  - Mitochondrial DNA mutations regulate metastasis of human breast cancer cells.
AB  - Mutations in mitochondrial DNA (mtDNA) might contribute to expression of the
      tumor phenotypes, such as metastatic potential, as well as to aging phenotypes
      and to clinical phenotypes of mitochondrial diseases by induction of
      mitochondrial respiration defects and the resultant overproduction of reactive
      oxygen species (ROS). To test whether mtDNA mutations mediate metastatic pathways
      in highly metastatic human tumor cells, we used human breast carcinoma MDA-MB-231
      cells, which simultaneously expressed a highly metastatic potential,
      mitochondrial respiration defects, and ROS overproduction. Since mitochondrial
      respiratory function is controlled by both mtDNA and nuclear DNA, it is possible
      that nuclear DNA mutations contribute to the mitochondrial respiration defects
      and the highly metastatic potential found in MDA-MB-231 cells. To examine this
      possibility, we carried out mtDNA replacement of MDA-MB-231 cells by normal human
      mtDNA. For the complete mtDNA replacement, first we isolated mtDNA-less (rho(0))
      MDA-MB-231 cells, and then introduced normal human mtDNA into the rho(0) MDA-MB
      231 cells, and isolated trans-mitochondrial cells (cybrids) carrying nuclear DNA
      from MDA-MB-231 cells and mtDNA from a normal subject. The normal mtDNA transfer
      simultaneously induced restoration of mitochondrial respiratory function and
      suppression of the highly metastatic potential expressed in MDA-MB-231 cells, but
      did not suppress ROS overproduction. These observations suggest that
      mitochondrial respiration defects observed in MDA-MB-231 cells are caused by
      mutations in mtDNA but not in nuclear DNA, and are responsible for expression of
      the high metastatic potential without using ROS-mediated pathways. Thus, human
      tumor cells possess an mtDNA-mediated metastatic pathway that is required for
      expression of the highly metastatic potential in the absence of ROS production.

PMID- 21853129
TI  - Theory of electric resonance in the neocortical apical dendrite.
AB  - Pyramidal neurons of the neocortex display a wide range of synchronous EEG
      rhythms, which arise from electric activity along the apical dendrites of
      neocortical pyramidal neurons. Here we present a theoretical description of
      oscillation frequency profiles along apical dendrites which exhibit resonance
      frequencies in the range of 10 to 100 Hz. The apical dendrite is modeled as a
      leaky coaxial cable coated with a dielectric, in which a series of compartments
      act as coupled electric circuits that gradually narrow the resonance profile. The
      tuning of the peak frequency is assumed to be controlled by the average amplitude
      of voltage-gated outward currents, which in turn are regulated by the
      subthreshold noise in the thousands of synaptic spines that are continuously
      bombarded by local circuits. The results of simulations confirmed the ability of
      the model both to tune the peak frequency in the 10-100 Hz range and to gradually
      narrow the resonance profile. Considerable additional narrowing of the resonance
      profile is provided by repeated looping through the apical dendrite via the
      corticothalamocortical circuit, which reduced the width of each resonance curve
      (at half-maximum) to approximately 1 Hz. Synaptic noise in the neural circuit is
      discussed in relation to the ways it can influence the narrowing process.

PMID- 21853130
TI  - Successful establishment of an orthotopic hepatoblastoma in vivo model in
      NOD/LtSz-scid IL2Rgammanull mice.
AB  - Investigation of hepatoblastoma in experimental conditions contributes relevantly
      to a detailed understanding of tumor biology and the investigation of new
      treatment approaches. Most systematical analyses currently use subcutaneous
      xenografts. We established a reproducible intrahepatic model with the
      hepatoblastoma-cell lines HuH6 and HepT1. The cells were stably transfected with
      a plasmid vector encoding for Gaussia luciferase. HuH6 and HepT1 were injected
      intrasplenically in NOD/LtSz-scid IL2Rgammanull mice. Mice were splenectomized in
      order to avoid intrasplenical tumor growth. Multifocal intrahepatic tumor growth
      was observed in 85% (11/13) of HuH6 tumors and 55% (5/9) of HepT1 tumors. Serum
      Alpha-fetoprotein and Gaussia luciferase increased 5 weeks after tumor-cell
      inoculation. Tumors were detected by MRI at this time point. Immunhistochemical
      analysis such as vascularity (CD31), proliferation index (Ki-67), cytokeratin 7
      and distribution of beta-catenin in intrahepatic tumors were different to
      subcutaneous tumors. We established a reproducible xenograft model for
      intrahepatic hepatoblastoma growth with a high tumor incidence. Monitoring of
      tumor cell viability was optimized by measuring GLuc. This model enables further
      experimental investigations of HB in a more physiological milieu as emphasized by
      the beta-catenin distribution.

PMID- 21853131
TI  - Axotomy-induced miR-21 promotes axon growth in adult dorsal root ganglion
      neurons.
AB  - Following injury, dorsal root ganglion (DRG) neurons undergo transcriptional
      changes so as to adopt phenotypic changes that promote cell survival and axonal
      regeneration. Here we used a microarray approach to profile changes in a
      population of small noncoding RNAs known as microRNAs (miRNAs) in the L4 and L5
      DRG following sciatic nerve transection. Results showed that 20 miRNA transcripts
      displayed a significant change in expression levels, with 8 miRNAs transcripts
      being altered by more than 1.5-fold. Using quantitative reverse transcription
      PCR, we demonstrated that one of these miRNAs, miR-21, was upregulated by 7-fold
      in the DRG at 7 days post-axotomy. In dissociated adult rat DRG neurons
      lentiviral vector-mediated overexpression of miR-21 promoted neurite outgrowth on
      a reduced laminin substrate. miR-21 directly downregulated expression of Sprouty2
      protein, as confirmed by Western blot analysis and 3' untranslated region (UTR)
      luciferase assays. Our data show that miR-21 is an axotomy-induced miRNA that
      enhances axon growth, and suggest that miRNAs are important players in regulating
      growth pathways following peripheral nerve injury.

PMID- 21853132
TI  - Metabolomics-driven nutraceutical evaluation of diverse green tea cultivars.
AB  - BACKGROUND: Green tea has various health promotion effects. Although there are
      numerous tea cultivars, little is known about the differences in their
      nutraceutical properties. Metabolic profiling techniques can provide information
      on the relationship between the metabolome and factors such as phenotype or
      quality. Here, we performed metabolomic analyses to explore the relationship
      between the metabolome and health-promoting attributes (bioactivity) of diverse
      Japanese green tea cultivars. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the
      ability of leaf extracts from 43 Japanese green tea cultivars to inhibit thrombin
      induced phosphorylation of myosin regulatory light chain (MRLC) in human
      umbilical vein endothelial cells (HUVECs). This thrombin-induced phosphorylation
      is a potential hallmark of vascular endothelial dysfunction. Among the tested
      cultivars, Cha Chuukanbohon Nou-6 (Nou-6) and Sunrouge (SR) strongly inhibited
      MRLC phosphorylation. To evaluate the bioactivity of green tea cultivars using a
      metabolomics approach, the metabolite profiles of all tea extracts were
      determined by high-performance liquid chromatography-mass spectrometry (LC-MS).
      Multivariate statistical analyses, principal component analysis (PCA) and
      orthogonal partial least-squares-discriminant analysis (OPLS-DA), revealed
      differences among green tea cultivars with respect to their ability to inhibit
      MRLC phosphorylation. In the SR cultivar, polyphenols were associated with its
      unique metabolic profile and its bioactivity. In addition, using partial least
      squares (PLS) regression analysis, we succeeded in constructing a reliable
      bioactivity-prediction model to predict the inhibitory effect of tea cultivars
      based on their metabolome. This model was based on certain identified metabolites
      that were associated with bioactivity. When added to an extract from the non
      bioactive cultivar Yabukita, several metabolites enriched in SR were able to
      transform the extract into a bioactive extract. CONCLUSIONS/SIGNIFICANCE: Our
      findings suggest that metabolic profiling is a useful approach for nutraceutical
      evaluation of the health promotion effects of diverse tea cultivars. This may
      propose a novel strategy for functional food design.

PMID- 21853133
TI  - Designing of highly effective complementary and mismatch siRNAs for silencing a
      gene.
AB  - In past, numerous methods have been developed for predicting efficacy of short
      interfering RNA (siRNA). However these methods have been developed for predicting
      efficacy of fully complementary siRNA against a gene. Best of author's knowledge
      no method has been developed for predicting efficacy of mismatch siRNA against a
      gene. In this study, a systematic attempt has been made to identify highly
      effective complementary as well as mismatch siRNAs for silencing a gene.Support
      vector machine (SVM) based models have been developed for predicting efficacy of
      siRNAs using composition, binary and hybrid pattern siRNAs. We achieved maximum
      correlation 0.67 between predicted and actual efficacy of siRNAs using hybrid
      model. All models were trained and tested on a dataset of 2182 siRNAs and
      performance was evaluated using five-fold cross validation techniques. The
      performance of our method desiRm is comparable to other well-known methods. In
      this study, first time attempt has been made to design mutant siRNAs (mismatch
      siRNAs). In this approach we mutated a given siRNA on all possible
      sites/positions with all possible nucleotides. Efficacy of each mutated siRNA is
      predicted using our method desiRm. It is well known from literature that
      mismatches between siRNA and target affects the silencing efficacy. Thus we have
      incorporated the rules derived from base mismatches experimental data to find out
      over all efficacy of mutated or mismatch siRNAs. Finally we developed a
      webserver, desiRm (http://www.imtech.res.in/raghava/desirm/) for designing highly
      effective siRNA for silencing a gene. This tool will be helpful to design siRNA
      to degrade disease isoform of heterozygous single nucleotide polymorphism gene
      without depleting the wild type protein.

PMID- 21853134
TI  - Sequencing of DISC1 pathway genes reveals increased burden of rare missense
      variants in schizophrenia patients from a northern Swedish population.
AB  - In recent years, DISC1 has emerged as one of the most credible and best supported
      candidate genes for schizophrenia and related neuropsychiatric disorders.
      Furthermore, increasing evidence--both genetic and functional--indicates that
      many of its protein interaction partners are also involved in the development of
      these diseases. In this study, we applied a pooled sample 454 sequencing
      strategy, to explore the contribution of genetic variation in DISC1 and 10 of its
      interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1,
      YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern
      Swedish population. Mutation burden analysis of the identified variants in a
      population of 486 SZ patients and 514 control individuals, revealed that non
      synonymous rare variants with a MAF<0.01 were significantly more present in
      patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further
      evidence for the involvement of DISC1 and some of its interaction partners in
      psychiatric disorders. This increased burden of rare missense variants was even
      more striking in a subgroup of early onset patients (12.9% versus 4.7%, P =
      0.0004), highlighting the importance of studying subgroups of patients and
      identifying endophenotypes. Upon investigation of the potential functional
      effects associated with the identified missense variants, we found that ~90% of
      these variants reside in intrinsically disordered protein regions. The observed
      increase in mutation burden in patients provides further support for the role of
      the DISC1 pathway in schizophrenia. Furthermore, this study presents the first
      evidence supporting the involvement of mutations within intrinsically disordered
      protein regions in the pathogenesis of psychiatric disorders. As many important
      biological functions depend directly on the disordered state, alteration of this
      disorder in key pathways may represent an intriguing new disease mechanism for
      schizophrenia and related neuropsychiatric diseases. Further research into this
      unexplored domain will be required to elucidate the role of the identified
      variants in schizophrenia etiology.

PMID- 21853135
TI  - A novel molecular signature identified by systems genetics approach predicts
      prognosis in oral squamous cell carcinoma.
AB  - Molecular methods for predicting prognosis in patients with oral cavity squamous
      cell carcinoma (OSCC) are urgently needed, considering its high recurrence rate
      and tendency for metastasis. The present study investigated the genetic basis of
      variations in gene expression associated with poor prognosis in OSCC using
      Affymetrix SNP 6.0 and Affymetrix GeneChip Human Gene 1.0 ST arrays. We
      identified recurrent DNA amplifications scattered from 8q22.2 to 8q24.3 in 112
      OSCC specimens. These amplicons demonstrated significant associations with
      increased incidence of extracapsular spread, development of second primary
      malignancies, and poor survival. Fluorescence in situ hybridization, in a
      validation panel consisting of 295 cases, confirmed these associations.
      Assessment of the effects of copy number variations (CNVs) on genome-wide
      variations in gene expression identified a total of 85 CNV-associated transcripts
      enriched in the MYC-centered regulatory network. Twenty-four transcripts
      associated with increased risk of second primary malignancies, tumor relapse, and
      poor survival. Besides MYC itself, a novel dysregulated MYC module plays a key
      role in OSCC carcinogenesis. This study identified a candidate molecular
      signature associated with poor prognosis in OSCC patients, which may ultimately
      facilitate patient-tailored selection of therapeutic strategies.

PMID- 21853136
TI  - Associations between rotating night shifts, sleep duration, and telomere length
      in women.
AB  - BACKGROUND: Telomere length has been proposed as a marker of aging. However, our
      knowledge of lifestyle risk factors determining telomere length is limited.
      METHODS: We evaluated the associations between years of rotating night shifts,
      self-reported sleep duration, and telomere length in 4,117 female participants
      from the Nurses' Health Study. Telomere length in peripheral blood leukocytes was
      determined by Real-Time PCR assay. Information on rotating night shifts and sleep
      duration was collected via questionnaires prior to blood collection. We used
      multivariable linear regression to investigate the associations between rotating
      night shifts, sleep duration, and telomere length. RESULTS: Compared with women
      in the category (9 hours), those in the lowest category of sleep duration (<=6
      hours) had a 0.12 unit decrease in z score after adjustment for age, BMI and
      cigarette smoking (equivalent to 9-year telomere attrition, P for trend  = 0.05).
      Significant positive association between sleep duration and telomere length was
      seen among women under age of 50 (P for trend  = 0.004), but not among those over
      50 (P for trend  = 0.33) (P for interaction  = 0.005). In addition, we observed
      that women with a longer history of rotating night shifts tended to have shorter
      telomere length, but this relation was not statistically significant (P for trend
      = 0.36). CONCLUSION: We found that sleep duration was positively associated with
      telomere length among women under 50 years old. Further research is needed to
      confirm the observed associations.

PMID- 21853137
TI  - Formation of AAV single stranded DNA genome from a circular plasmid in
      Saccharomyces cerevisiae.
AB  - Adeno-associated virus (AAV)-based vectors are promising tools for targeted
      transfer in gene therapy studies. Many efforts have been accomplished to improve
      production and purification methods. We thought to develop a simple eukaryotic
      system allowing AAV replication which could provide an excellent opportunity for
      studying AAV biology and, more importantly, for AAV vector production. It has
      been shown that yeast Saccharomyces cerevisiae is able to replicate and form the
      capsid of many viruses. We investigated the ability of the yeast Saccharomyces
      cerevisiae to carry out the replication of a recombinant AAV (rAAV). When a
      plasmid containing a rAAV genome in which the cap gene was replaced with the S.
      cerevisiae URA3 gene, was co-transformed in yeast with a plasmid expressing
      Rep68, a significant number of URA3(+) clones were scored (more than 30-fold over
      controls). Molecular analysis of low molecular weight DNA by Southern blotting
      revealed that single stranded DNA is formed and that the plasmid is entirely
      replicated. The ssDNA contains the ITRs, URA3 gene and also vector sequences
      suggesting the presence of two distinct molecules. Its formation was dependent on
      Rep68 expression and ITR. These data indicate that DNA is not obtained by the
      canonical AAV replication pathway.

PMID- 21853139
TI  - Fumonisin and ochratoxin production in industrial Aspergillus niger strains.
AB  - Aspergillus niger is perhaps the most important fungus used in biotechnology, and
      is also one of the most commonly encountered fungi contaminating foods and
      feedstuffs, and occurring in soil and indoor environments. Many of its industrial
      applications have been given GRAS status (generally regarded as safe). However,
      A. niger has the potential to produce two groups of potentially carcinogenic
      mycotoxins: fumonisins and ochratoxins. In this study all available industrial
      and many non-industrial strains of A. niger (180 strains) as well as 228 strains
      from 17 related black Aspergillus species were examined for mycotoxin production.
      None of the related 17 species of black Aspergilli produced fumonisins.
      Fumonisins (B(2), B(4), and B(6)) were detected in 81% of A. niger, and
      ochratoxin A in 17%, while 10% of the strains produced both mycotoxins. Among the
      industrial strains the same ratios were 83%, 33% and 26% respectively. Some of
      the most frequently used strains in industry NRRL 337, 3112 and 3122 produced
      both toxins and several strains used for citric acid production were among the
      best producers of fumonisins in pure agar culture. Most strains used for other
      biotechnological processes also produced fumonisins. Strains optimized through
      random mutagenesis usually maintained their mycotoxin production capability.
      Toxigenic strains were also able to produce the toxins on media suggested for
      citric acid production with most of the toxins found in the biomass, thereby
      questioning the use of the remaining biomass as animal feed. In conclusion it is
      recommended to use strains of A. niger with inactive or inactivated gene clusters
      for fumonisins and ochratoxins, or to choose isolates for biotechnological uses
      in related non-toxigenic species such as A. tubingensis, A. brasiliensis, A
      vadensis or A. acidus, which neither produce fumonisins nor ochratoxins.

PMID- 21853138
TI  - Multiple distinct stimuli increase measured nucleosome occupancy around human
      promoters.
AB  - Nucleosomes can block access to transcription factors. Thus the precise
      localization of nucleosomes relative to transcription start sites and other
      factor binding sites is expected to be a critical component of transcriptional
      regulation. Recently developed microarray approaches have allowed the rapid
      mapping of nucleosome positions over hundreds of kilobases (kb) of human genomic
      DNA, although these approaches have not yet been widely used to measure chromatin
      changes associated with changes in transcription. Here, we use custom tiling
      microarrays to reveal changes in nucleosome positions and abundance that occur
      when hormone-bound glucocorticoid receptor (GR) binds to sites near target gene
      promoters in human osteosarcoma cells. The most striking change is an increase in
      measured nucleosome occupancy at sites spanning ~1 kb upstream and downstream of
      transcription start sites, which occurs one hour after addition of hormone, but
      is lost at 4 hours. Unexpectedly, this increase was seen both on GR-regulated and
      GR-non-regulated genes. In addition, the human SWI/SNF chromatin remodeling
      factor (a GR co-activator) was found to be important for increased occupancy upon
      hormone treatment and also for low nucleosome occupancy without hormone. Most
      surprisingly, similar increases in nucleosome occupancy were also seen on both
      regulated and non-regulated promoters during differentiation of human myeloid
      leukemia cells and upon activation of human CD4+ T-cells. These results indicate
      that dramatic changes in chromatin structure over ~2 kb of human promoters may
      occur genomewide and in response to a variety of stimuli, and suggest novel
      models for transcriptional regulation.

PMID- 21853140
TI  - Rhabdomyosarcomas in aging A/J mice.
AB  - Rhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and
      domestic mammals. The A/J inbred strain developed a high frequency (between 70
      80%) of adult pleomorphic type (APT) RSC at >20 months of age while BALB/cByJ
      also develop RSC but less frequently. These neoplasms invaded skeletal muscle
      surrounding either the axial or proximal appendicular skeleton and were
      characterized by pleomorphic cells with abundant eosinophilic cytoplasm, multiple
      nuclei, and cross striations. The diagnosis was confirmed by detection of alpha
      sarcomeric actin and myogenin in the neoplastic cells using immunocytochemistry.
      The A/J strain, but not the related BALB/c substrains, is also characterised by a
      progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type
      2B. The association between the development of RSC in similar muscle groups to
      those most severely affected by the progressive muscular dystrophy suggested that
      these neoplasms developed from abnormal regeneration of the skeletal muscle
      exacerbated by the dysferlin mutation. Transcriptome analyses of RSCs revealed
      marked downregulation of genes in muscular development and function signaling
      networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and
      Kcnj12 suggesting these may be important in the pathogenesis of RSC. These
      studies suggest that A strains of mice can be useful models for dissecting the
      molecular genetic basis for development, progression, and ultimately for testing
      novel anticancer therapeutic agents dealing with rhabdomyosarcoma.

PMID- 21853141
TI  - Evolution of cagA oncogene of Helicobacter pylori through recombination.
AB  - Helicobacter pylori is a gastric pathogen that infects half the human population
      and causes gastritis, ulcers, and cancer. The cagA gene product is a major
      virulence factor associated with gastric cancer. It is injected into epithelial
      cells, undergoes phosphorylation by host cell kinases, and perturbs host
      signaling pathways. CagA is known for its geographical, structural, and
      functional diversity in the C-terminal half, where an EPIYA host-interacting
      motif is repeated. The Western version of CagA carries the EPIYA segment types A,
      B, and C, while the East Asian CagA carries types A, B, and D and shows higher
      virulence. Many structural variants such as duplications and deletions are
      reported. In this study, we gained insight into the relationships of CagA
      variants through various modes of recombination, by analyzing all known cagA
      variants at the DNA sequence level with the single nucleotide resolution.
      Processes that occurred were: (i) homologous recombination between DNA sequences
      for CagA multimerization (CM) sequence; (ii) recombination between DNA sequences
      for the EPIYA motif; and (iii) recombination between short similar DNA sequences.
      The left half of the EPIYA-D segment characteristic of East Asian CagA was
      derived from Western type EPIYA, with Amerind type EPIYA as the intermediate,
      through rearrangements of specific sequences within the gene. Adaptive amino acid
      changes were detected in the variable region as well as in the conserved region
      at sites to which no specific function has yet been assigned. Each showed a
      unique evolutionary distribution. These results clarify recombination-mediated
      routes of cagA evolution and provide a solid basis for a deeper understanding of
      its function in pathogenesis.

PMID- 21853142
TI  - Comparative analysis of salivary bacterial microbiome diversity in edentulous
      infants and their mothers or primary care givers using pyrosequencing.
AB  - Bacterial contribution to oral disease has been studied in young children, but
      there is a lack of data addressing the developmental perspective in edentulous
      infants. Our primary objectives were to use pyrosequencing to phylogenetically
      characterize the salivary bacterial microbiome of edentulous infants and to make
      comparisons against their mothers. Saliva samples were collected from 5
      edentulous infants (mean age = 4.6+/-1.2 mo old) and their mothers or primary
      care givers (mean age = 30.8+/-9.5 y old). Salivary DNA was extracted, used to
      generate DNA amplicons of the V4-V6 hypervariable region of the bacterial 16S
      rDNA gene, and subjected to 454-pyrosequencing. On average, over 80,000 sequences
      per sample were generated. High bacterial diversity was noted in the saliva of
      adults [1012 operational taxonomical units (OTU) at 3% divergence] and infants
      (578 OTU at 3% divergence). Firmicutes, Proteobacteria, Actinobacteria, and
      Fusobacteria were predominant bacterial phyla present in all samples. A total of
      397 bacterial genera were present in our dataset. Of the 28 genera different
      (P<0.05) between infants and adults, 27 had a greater prevalence in adults. The
      exception was Streptococcus, which was the predominant genera in infant saliva
      (62.2% in infants vs. 20.4% in adults; P<0.05). Veillonella, Neisseria, Rothia,
      Haemophilus, Gemella, Granulicatella, Leptotrichia, and Fusobacterium were also
      predominant genera in infant samples, while Haemophilus, Neisseria, Veillonella,
      Fusobacterium, Oribacterium, Rothia, Treponema, and Actinomyces were predominant
      in adults. Our data demonstrate that although the adult saliva bacterial
      microbiome had a greater OTU count than infants, a rich bacterial community
      exists in the infant oral cavity prior to tooth eruption. Streptococcus,
      Veillonella, and Neisseria are the predominant bacterial genera present in
      infants. Further research is required to characterize the development of oral
      microbiota early in life and identify environmental factors that impact
      colonization and oral and gastrointestinal disease risk.

PMID- 21853143
TI  - Molecular genetic analyses of polytene chromosome region 72A-D in Drosophila
      melanogaster reveal a gene desert in 72D.
AB  - We have investigated a region of ~310 kb of genomic DNA within polytene
      chromosome subdivisions 72A to 72D of Drosophila melanogaster. This region
      includes 57 predicted protein-coding genes. Seventeen of these genes are in six
      clusters that appear to have arisen by tandem duplication. Within this region we
      found 23 complementation groups that are essential for zygotic viability, and we
      have identified the transcription units for 18 of the 23. We also found a 55 kb
      region in 72D that is nonessential. Flies deficient for this region are viable
      and fertile. Within this nonessential region are 48 DNA sequences of 12 to 33
      base pairs that are completely conserved among 12 distantly related Drosophila
      species. These sequences do not have the evolutionary signature of conserved
      protein-coding DNA sequences, nor do they appear to encode microRNAs, however,
      the strong selection suggests functions in wild populations that are not apparent
      in laboratory cultures. This region resembles dispensable gene deserts previously
      characterized in the mouse genome.

PMID- 21853145
TI  - Identification and phylogenetic analysis of heme synthesis genes in
      trypanosomatids and their bacterial endosymbionts.
AB  - It has been known for decades that some insect-infecting trypanosomatids can
      survive in culture without heme supplementation while others cannot, and that
      this capability is associated with the presence of a betaproteobacterial
      endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms
      involved in this process remained obscure. In this work, we sequence and
      phylogenetically analyze the heme pathway genes from the symbionts and from their
      hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our
      results show that the enzymes responsible for synthesis of heme are encoded on
      the symbiont genomes and produced in close cooperation with the flagellate host.
      Our evidence suggests that this synergistic relationship is the end result of a
      history of extensive gene loss and multiple lateral gene transfer events in
      different branches of the phylogeny of the Trypanosomatidae.

PMID- 21853144
TI  - An atypical unfolded protein response in heat shocked cells.
AB  - BACKGROUND: The heat shock response (HSR) and the unfolded protein response (UPR)
      are both activated by proteotoxic stress, although in different compartments, and
      share cellular resources. How these resources are allocated when both responses
      are active is not known. Insight in possible crosstalk will help understanding
      the consequences of failure of these systems in (age-related) disease. RESULTS:
      In heat stressed HEK293 cells synthesis of the canonical UPR transcription
      factors XBP1s and ATF4 was detected as well as HSF1 independent activation of the
      promoters of the ER resident chaperones HSPA5 (BiP) and DNAJB9 (ERdj4). However,
      the heat stress activation of the DNAJB9 promoter, a XBP1s target, was not
      blocked in cells expressing a dominant negative IRE1alpha mutant, and thus did
      not require XBP1s. Furthermore, the DNA element required for heat stress
      activation of the DNAJB9 promoter is distinct from the ATF4 and ATF6 target
      elements; even though inhibition of eIF2alpha phosphorylation resulted in a
      decreased activation of the DNAJB9 promoter upon heat stress, suggesting a role
      for an eIF2alpha phosphorylation dependent product. CONCLUSIONS: The initial step
      in the UPR, synthesis of transcription factors, is activated by heat stress but
      the second step, transcriptional transactivation by these factors, is blocked and
      these pathways of the UPR are thus not productive. Expression of canonical ER
      chaperones is part of the response of heat stressed cells but another set of
      transcription factors has been recruited to regulate expression of these ER
      chaperones.

PMID- 21853146
TI  - Radiolaria divided into Polycystina and Spasmaria in combined 18S and 28S rDNA
      phylogeny.
AB  - Radiolarians are marine planktonic protists that belong to the eukaryote
      supergroup Rhizaria together with Foraminifera and Cercozoa. Radiolaria has
      traditionally been divided into four main groups based on morphological
      characters; i.e. Polycystina, Acantharia, Nassellaria and Phaeodaria. But recent
      18S rDNA phylogenies have shown that Phaeodaria belongs within Cerocozoa, and
      that the previously heliozoan group Taxopodida should be included in Radiolaria.
      18S rDNA phylogenies have not yet resolved the sister relationship between the
      main Radiolaria groups, but nevertheless suggests that Spumellaria, and thereby
      also Polycystina, are polyphyletic. Very few sequences other than 18S rDNA have
      so far been generated from radiolarian cells, mostly due to the fact that
      Radiolaria has been impossible to cultivate and single cell PCR has been hampered
      by low success rate. Here we have therefore investigated the mutual evolutionary
      relationship of the main radiolarian groups by using the novel approach of
      combining single cell whole genome amplification with targeted PCR amplification
      of the 18S and 28S rDNA genes. Combined 18S and 28S phylogeny of sequences
      obtained from single cells shows that Radiolaria is divided into two main
      lineages: Polycystina (Spumellaria+Nassellaria) and Spasmaria
      (Acantharia+Taxopodida). Further we show with high support that Foraminifera
      groups within Radiolaria supporting the Retaria hypothesis.

PMID- 21853147
TI  - Phylogenetically clustered extinction risks do not substantially prune the Tree
      of Life.
AB  - Anthropogenic activities have increased the rate of biological extinction many
      fold. Recent empirical studies suggest that projected extinction may lead to
      extensive loss to the Tree of Life, much more than if extinction were random. One
      suggested cause is that extinction risk is heritable (phylogenetically
      patterned), such that entire higher groups will be lost. We show here with
      simulation that phylogenetically clustered extinction risks are necessary but not
      sufficient for the extensive loss of phylogenetic diversity (PD) compared to
      random extinction. We simulated Yule trees and evolved extinction risks at
      various levels of heritability (measured using Pagel's lambda). At most levels of
      heritability (lambda in range of 0 to 10), mean values of extinction risk (range
      0.25 to 0.75), tree sizes (64 to 128 tips), tree balance and temporal
      heterogeneity of diversification rates (Yule and coalescent trees), extinction
      risks do not substantially increase the loss of PD in these trees when compared
      to random extinction. The maximum loss of PD (20% above random) was only
      associated with the combination of extremely excessive values of phylogenetic
      signal, high mean species' extinction probabilities, and extreme (coalescent)
      tree shapes. Interestingly, we also observed a decline in the rate of increase in
      the loss of PD at high phylogenetic clustering (lambda -> 10) of extinction
      risks. Our results suggest that the interplay between various aspects of tree
      shape and a predisposition of higher extinction risks in species-poor clades is
      required to explain the substantial pruning of the Tree of Life.

PMID- 21853148
TI  - Somaclonal variation is induced de novo via the tissue culture process: a study
      quantifying mutated cells in Saintpaulia.
AB  - BACKGROUND: The origin of somaclonal variation has not been questioned
      previously, i.e., "pre-existing mutations" in explants and "newly induced
      mutations" arising from the tissue culture process have not been distinguished.
      This is primarily because there has been no reliable molecular method for
      estimating or quantifying variation. METHODOLOGY/PRINCIPAL FINDINGS: We adopted a
      petal-variegated cultivar of Saintpaulia 'Thamires' (Saintpaulia sp.) as the
      model plant. Based on the difference between the pre- and post-transposon
      excision sequence of the promoter region of flavonoid 3', 5'-hydoroxylase
      (F3'5'H), we estimated mutated (transposon-excised) cell percentages using a
      quantitative real-time PCR. Mutated cell percentages in leaf laminae used as
      explants was 4.6 and 2.4% in highly or low variegation flower plants,
      respectively, although the occurrences of blue color mutants in their regenerants
      were more than 40%. Preexisting mutated cell percentages in cultured explants
      were considerably lower than the mutated plant percentage among total regenerants
      via tissue culture. CONCLUSIONS/SIGNIFICANCE: The estimation of mutated cell
      percentages became possible using the quantitative real-time PCR. The origins of
      mutations were successfully distinguished; it was confirmed that somaclonal
      variations are mainly caused by newly generated mutations arising from tissue
      culture process.

PMID- 21853149
TI  - Complement opsonization of HIV-1 enhances the uptake by dendritic cells and
      involves the endocytic lectin and integrin receptor families.
AB  - Interaction with the complement system is an underappreciated aspect of HIV-1
      infection; even in primary infection, complement fragments are found on virions
      with potential to affect the interplay between the virus and dendritic cells
      (DC). Since opsonization may affect the efficiency of uptake and the type of
      receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV)
      and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly
      enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the
      internalization rate was dependent on both opsonization of the virus and DC
      maturation state. Increased DC uptake of C-HIV was not due to opsonization
      related increased binding of virus to the surface of DC but rather increased
      internalization of C-HIV despite utilizing a similar repertoire of receptors as F
      HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and
      blocking these receptor families prevented HIV-1 from binding to DC at 4 degrees
      C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C
      HIV implicating the involvement of several integrins such as beta1-integrin, CR3,
      LFA-1, and alpha4beta7. Distinctive for C-HIV was usage of beta1-integrin and for
      F-HIV, usage of beta7-integrin, whereas both F-HIV and C-HIV utilized both
      integrin chains of CR3. We have in this study identified the receptor types used
      by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more
      efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which
      may entail different intracellular processing of the virus leading to both
      elevated infection and altered activation of HIV specific immune responses.

PMID- 21853150
TI  - Increased endothelial cell-leukocyte interaction in murine schistosomiasis:
      possible priming of endothelial cells by the disease.
AB  - BACKGROUND AND AIMS: Schistosomiasis is an intravascular parasitic disease
      associated with inflammation. Endothelial cells control leukocyte transmigration
      and vascular permeability being modulated by pro-inflammatory mediators. Recent
      data have shown that endothelial cells primed in vivo in the course of a disease
      keep the information in culture. Herein, we evaluated the impact of
      schistosomiasis on endothelial cell-regulated events in vivo and in vitro.
      METHODOLOGY AND PRINCIPAL FINDINGS: The experimental groups consisted of
      Schistosoma mansoni-infected and age-matched control mice. In vivo infection
      caused a marked influx of leukocytes and an increased protein leakage in the
      peritoneal cavity, characterizing an inflamed vascular and cellular profile. In
      vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells
      from infected mice as compared to controls, either in the basal condition or
      after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF).
      Nitric oxide (NO) donation reduced leukocyte adhesion to endothelial cells from
      control and infected groups; however, in the later group the effect was more
      pronounced, probably due to a reduced NO production. Inhibition of control
      endothelial NO synthase (eNOS) increased leukocyte adhesion to a level similar to
      the one observed in the infected group. Besides, the adhesion of control
      leukocytes to endothelial cells from infected animals is similar to the result of
      infected animals, confirming that schistosomiasis alters endothelial cells
      function. Furthermore, NO production as well as the expression of eNOS were
      reduced in cultured endothelial cells from infected animals. On the other hand,
      the expression of its repressor protein, namely caveolin-1, was similar in both
      control and infected groups. CONCLUSION/SIGNIFICANCE: Schistosomiasis increases
      vascular permeability and endothelial cell-leukocyte interaction in vivo and in
      vitro. These effects are partially explained by a reduced eNOS expression. In
      addition, our data show that the disease primes endothelial cells in vivo, which
      keep the acquired phenotype in culture.

PMID- 21853151
TI  - Size matters: non-numerical magnitude affects the spatial coding of response.
AB  - It is known that small and large numbers facilitate left/right respectively (the
      SNARC effect). Recently, it has been proposed that numerical magnitude is just
      one example of a range of quantities, which have a common cognitive/neural
      representation. To investigate this proposition, response congruency effects were
      explored for stimuli which differed according to their: (a) numerical size, (b)
      physical size, (c) luminance, (d) conceptual size and (e) auditory intensity. In
      a series of experiments, groups of undergraduate participants made two
      alternative forced choice discriminations with their left or right hands. There
      were clear interactions between magnitude and responding hand whereby right hand
      responses were faster for stimuli with (a) large numbers, (b) large physical
      size, (c) low luminance, and (d) a reference to large objects. There was no
      congruency effect for the auditory stimuli. The data demonstrate that the
      response congruency effect observed for numbers also occurs for a variety of
      other non-numerical visual quantities. These results support models of general
      magnitude representation and suggest that the association between magnitude and
      the left/right sides of space may not be related to culture and/or directional
      reading habits.

PMID- 21853152
TI  - In vitro and in vivo activity of ribavirin against Andes virus infection.
AB  - Pathogenic hantaviruses are a closely related group of rodent-borne viruses which
      are responsible for two distinct diseases in humans, hemorrhagic fever with renal
      syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus
      cardiopulmonary syndrome, HCPS). The antiviral effect of ribavirin against Old
      World hantaviruses, most notably Hantaan virus, is well documented; however, only
      a few studies have addressed its inhibitory effect on New World hantaviruses. In
      the present study, we demonstrate that ribavirin is highly active against Andes
      virus (ANDV), an important etiological agent of HPS, both in vitro and in vivo
      using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells
      with ribavirin resulted in dose-dependent reductions in viral RNA and protein as
      well as virus yields with a half maximal inhibitory concentration between 5 and
      12.5 ug ml(-1). In hamsters, treatment with as little as 5 mg kg(-1) day(-1) was
      100% effective at preventing lethal HPS disease when therapy was administered by
      intraperitoneal injection from day 1 through day 10 post-infection. Significant
      reductions were observed in ANDV RNA and antigen positive cells in lung and liver
      tissues. Ribavirin remained completely protective when administered by
      intraperitoneal injections up to three days post-infection. In addition, we show
      that daily oral ribavirin therapy initiated 1 day post-infection and continuing
      for ten days is also protective against lethal ANDV disease, even at doses of 5
      mg kg(-1) day(-1). Our results suggest ribavirin treatment is beneficial for
      postexposure prophylaxis against HPS-causing hantaviruses and should be
      considered in scenarios where exposure to the virus is probable. The similarities
      between the results obtained in this study and those from previous clinical
      evaluations of ribavirin against HPS, further validate the hamster model of
      lethal HPS and demonstrate its usefulness in screening antiviral agents against
      this disease.

PMID- 21853153
TI  - Strategy to find molecular signatures in a small series of rare cancers:
      validation for radiation-induced breast and thyroid tumors.
AB  - Methods of classification using transcriptome analysis for case-by-case tumor
      diagnosis could be limited by tumor heterogeneity and masked information in the
      gene expression profiles, especially as the number of tumors is small. We propose
      a new strategy, EMts_2PCA, based on: 1) The identification of a gene expression
      signature with a great potential for discriminating subgroups of tumors (EMts
      stage), which includes: a) a learning step, based on an expectation-maximization
      (EM) algorithm, to select sets of candidate genes whose expressions discriminate
      two subgroups, b) a training step to select from the sets of candidate genes
      those with the highest potential to classify training tumors, c) the compilation
      of genes selected during the training step, and standardization of their levels
      of expression to finalize the signature. 2) The predictive classification of
      independent prospective tumors, according to the two subgroups of interest, by
      the definition of a validation space based on a two-step principal component
      analysis (2PCA). The present method was evaluated by classifying three series of
      tumors and its robustness, in terms of tumor clustering and prediction, was
      further compared with that of three classification methods (Gene expression bar
      code, Top-scoring pair(s) and a PCA-based method). Results showed that EMts_2PCA
      was very efficient in tumor classification and prediction, with scores always
      better that those obtained by the most common methods of tumor clustering.
      Specifically, EMts_2PCA permitted identification of highly discriminating
      molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy
      breast tumors from their sporadic counterparts that were previously
      unsuccessfully classified or classified with errors.

PMID- 21853154
TI  - Flanking bases influence the nature of DNA distortion by platinum 1,2-intrastrand
      (GG) cross-links.
AB  - The differences in efficacy and molecular mechanisms of platinum anti-cancer
      drugs cisplatin (CP) and oxaliplatin (OX) are thought to be partially due to the
      differences in the DNA conformations of the CP and OX adducts that form on
      adjacent guanines on DNA, which in turn influence the binding of damage
      recognition proteins that control downstream effects of the adducts. Here we
      report a comprehensive comparison of the structural distortion of DNA caused by
      CP and OX adducts in the TGGT sequence context using nuclear magnetic resonance
      (NMR) spectroscopy and molecular dynamics (MD) simulations. When compared to our
      previous studies in other sequence contexts, these structural studies help us
      understand the effect of the sequence context on the conformation of Pt-GG DNA
      adducts. We find that both the sequence context and the type of Pt-GG DNA adduct
      (CP vs. OX) play an important role in the conformation and the conformational
      dynamics of Pt-DNA adducts, possibly explaining their influence on the ability of
      many damage-recognition proteins to bind to Pt-DNA adducts.

PMID- 21853155
TI  - Let-7a is a direct EWS-FLI-1 target implicated in Ewing's sarcoma development.
AB  - Ewing's sarcoma family tumors (ESFT) are the second most common bone malignancy
      in children and young adults, characterized by unique chromosomal translocations
      that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI
      1 functions as an aberrant transcription factor that can both induce and suppress
      members of its target gene repertoire. We have recently demonstrated that EWS-FLI
      1 can alter microRNA (miRNA) expression and that miRNA145 is a direct EWS-FLI-1
      target whose suppression is implicated in ESFT development. Here, we use miRNA
      arrays to compare the global miRNA expression profile of human mesenchymal stem
      cells (MSC) and ESFT cell lines, and show that ESFT display a distinct miRNA
      signature that includes induction of the oncogenic miRNA 17-92 cluster and
      repression of the tumor suppressor let-7 family. We demonstrate that direct
      repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of
      ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth
      is shown to be mediated by its target gene HMGA2, as let-7a overexpression and
      HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these
      observations, systemic delivery of synthetic let-7a into ESFT-bearing mice
      restored its expression in tumor cells, decreased HMGA2 expression levels and
      resulted in ESFT growth inhibition in vivo. Our observations provide evidence
      that deregulation of let-7a target gene expression participates in ESFT
      development and identify let-7a as promising new therapeutic target for one of
      the most aggressive pediatric malignancies.

PMID- 21853156
TI  - An integrated Drosophila model system reveals unique properties for F14512, a
      novel polyamine-containing anticancer drug that targets topoisomerase II.
AB  - F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled
      to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to
      ensure the preferential uptake of F14512 by cancer cells, strong interaction with
      DNA and potent inhibition of topoisomerase II (Topo II). The antitumor activity
      of F14512 in human tumor models is significantly higher than that of other
      epipodophyllotoxins in spite of a lower induction of DNA breakage. Hence, the
      demonstrated superiority of F14512 over other Topo II poisons might not result
      solely from its preferential uptake by cancer cells, but could also be due to
      unique effects on Topo II interactions with DNA. To further dissect the mechanism
      of action of F14512, we used Drosophila melanogaster mutants whose genetic
      background leads to an easily scored phenotype that is sensitive to changes in
      Topo II activity and/or localization. F14512 has antiproliferative properties in
      Drosophila cells and stabilizes ternary Topo II/DNA cleavable complexes at unique
      sites located in moderately repeated sequences, suggesting that the drug
      specifically targets a select and limited subset of genomic sequences. Feeding
      F14512 to developing mutant Drosophila larvae led to the recovery of flies
      expressing a striking phenotype, "Eye wide shut," where one eye is replaced by a
      first thoracic segment. Other recovered F14512-induced gain- and loss-of-function
      phenotypes similarly correspond to precise genetic dysfunctions. These complex in
      vivo results obtained in a whole developing organism can be reconciled with known
      genetic anomalies and constitute a remarkable instance of specific alterations of
      gene expression by ingestion of a drug. "Drosophila-based anticancer
      pharmacology" hence reveals unique properties for F14512, demonstrating the
      usefulness of an assay system that provides a low-cost, rapid and effective
      complement to mammalian models and permits the elucidation of fundamental
      mechanisms of action of candidate drugs of therapeutic interest in humans.

PMID- 21853157
TI  - Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M
      MOK megakaryoblastic leukemic cell growth by promoting apoptosis.
AB  - BACKGROUND: Lnk plays a non-redundant role by negatively regulating cytokine
      signaling of TPO, SCF or EPO. Retroviral expression of Lnk has been shown to
      suppress hematopoietic leukemic cell proliferation indicating its therapeutic
      value in cancer therapy. However, retroviral gene delivery carries risks of
      insertional mutagenesis. To circumvent this undesired consequence, we fused a
      cell permeable peptide octa-arginine to Lnk and evaluated the efficacy of
      inhibition of leukemic cell proliferation in vitro. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, proliferation assays, flow cytometry, Western Blot
      analyses were performed on wild-type (WT), mutant Lnk R8 or BSA treated M-MOK
      cells. We found that delivered WT, but not mutant Lnk R8 blocked TPO-induced M
      MOK megakaryoblastic leukemic cell proliferation. In contrast, WT Lnk R8 showed
      no growth inhibitive effect on non-hematopoietic HELA or COS-7 cell. Moreover, we
      demonstrated that TPO-induced M-MOK cell growth inhibition by WT Lnk R8 was dose
      dependent. Penetrated WT Lnk R8 induced cell cycle arrest and apoptosis.
      Immunoprecipitation and Western blots data indicated WT Lnk R8 interacted with
      endogeneous Jak2 and downregulated Jak-Stat and MAPK phosphorylation level in M
      MOK cells after TPO stimulation. Treatment with specific inhibitors (TG101348 and
      PD98059) indicated Jak-Stat and MAPK pathways were crucial for TPO-induced
      proliferation of M-MOK cells. Further analyses using TF-1 and HEL leukemic cell
      lines showed that WT Lnk R8 inhibited Jak2-dependent cell proliferation. Using
      cord blood-derived CD34+ stem cells, we found that delivered WT Lnk R8 blocked
      TPO-induced megakaryopoiesis in vitro. CONCLUSIONS/SIGNIFICANCE: Intracellular
      delivery of WT Lnk R8 fusion protein efficiently inhibited TPO-induced M-MOK
      leukemic cell growth by promoting apoptosis. WT Lnk R8 protein delivery may
      provide a safer and more practical approach to inhibit leukemic cell growth
      worthy of further development.

PMID- 21853158
TI  - Metabolomic profile of hepatitis C virus-infected hepatocytes.
AB  - Hepatitis C virus (HCV) is capable of disrupting different facets of lipid
      metabolism and lipids have been shown to play a crucial role in the viral life
      cycle. The aim of this study was to examine the effect HCV infection has on the
      hepatocyte metabolome. Huh-7.5 cells were infected using virus produced by the
      HCV J6/JFH1 cell culture system and cells were harvested 24, 48, and 72-hours
      following infection. Metabolic profiling was performed using a non-targeted
      multiple platform methodology combining ultrahigh performance liquid
      chromatography/tandem mass spectrometry (UHPLC/MS/MS(2)) and gas
      chromatography/mass spectrometry (GC/MS). There was a significant increase in a
      number of metabolites involved in nucleotide synthesis and RNA replication during
      early HCV infection. NAD levels were also significantly increased along with
      several amino acids. A number of lipid metabolic pathways were disrupted by HCV
      infection, resulting in an increase in cholesterol and sphingolipid levels,
      altered phospholipid metabolism and a possible disruption in mitochondrial fatty
      acid transport. Fluctuations in 5'-methylthioadenosine levels were also noted,
      along with alterations in the glutathione synthesis pathway. These results
      highlight a number of previously unreported metabolic interactions and give a
      more in depth insight into the effect HCV has on host cell biochemical processes.

PMID- 21853159
TI  - Clinical Implications of Lipid Genetics for Cardiovascular Disease.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in the
      developed world. Epidemiologic data support a strong relationship of
      atherosclerotic cardiovascular disease (ASCVD) with both elevated low-density
      lipoprotein cholesterol (LDL-C), and reduced high-density lipoprotein cholesterol
      (HDL-C). The study of the human genetics of plasma lipid traits, both rare
      Mendelian disorders as well as common variants, has illuminated multiple genes
      and pathways involved in the regulation of LDL-C and HDL-C levels. Mendelian
      disorders of extremes of LDL-C and Mendelian randomization studies of common gene
      variants associated with LDL-C strongly support a causal relationship between LDL
      C and ASCVD, independent of mechanism. In contrast, Mendelian disorders of
      extremes of HDL-C and Mendelian randomization studies of common genetic variants
      for HDL-C are inconsistent in their support of a causal relationship between HDL
      C and ASCVD. In contrast to LDL-C, a causal relationship between HDL-C and ASCVD
      may be dependent on the specific mechanism leading to variation in HDL-C levels.

PMID- 21853160
TI  - Implementing an Interoperable Personal Health Record in Pediatrics: Lessons
      Learned at an Academic Children's Hospital.
AB  - This paper describes the development of an innovative health information
      technology creating a bidirectional link between the electronic medical record
      (EMR) of an academic children's hospital and a commercially available,
      interoperable personal health record (PHR). The goal of the PHR project has been
      to empower pediatric patients and their families to play a more active role in
      understanding, accessing, maintaining, and sharing their personal health
      information to ultimately improve health outcomes. The most notable challenges
      proved more operational and cultural than technological. Our experience
      demonstrates that an interoperable PHR is technically and culturally achievable
      at a pediatric academic medical center. Recognizing the complex social, cultural,
      and organizational contexts of these systems is important for overcoming barriers
      to a successful implementation.

PMID- 21853161
TI  - Multistage Mesoporous Silicon-based Nanocarriers: Biocompatibility with Immune
      Cells and Controlled Degradation in Physiological Fluids.

PMID- 21853162
TI  - The Upper and Lower Bounds of the Prediction Accuracies of Ensemble Methods for
      Binary Classification.
AB  - Ensemble methods have been widely used to improve prediction accuracy over
      individual classifiers. In this paper, we achieve a few results about the
      prediction accuracies of ensemble methods for binary classification that are
      missed or misinterpreted in previous literature. First we show the upper and
      lower bounds of the prediction accuracies (i.e. the best and worst possible
      prediction accuracies) of ensemble methods. Next we show that an ensemble method
      can achieve > 0.5 prediction accuracy, while individual classifiers have < 0.5
      prediction accuracies. Furthermore, for individual classifiers with different
      prediction accuracies, the average of the individual accuracies determines the
      upper and lower bounds. We perform two experiments to verify the results and show
      that it is hard to achieve the upper and lower bounds accuracies by random
      individual classifiers and better algorithms need to be developed.

PMID- 21853163
TI  - Role of an intrinsically disordered conformation in AMPK-mediated phosphorylation
      of ULK1 and regulation of autophagy.
AB  - Recently, it has been established that there is a direct link between adenosine
      monophosphate activated protein kinase (AMPK), which is an energy sensor and is
      activated by glucose starvation, and Unc-51-like kinase 1 (ULK1) in triggering
      autophagy. Proper phosphorylation of ULK1 is crucial for ULK1/AMPK association
      and subsequent ULK1 functions in response to nutrient deprivation. Signaling
      modulated via phosphorylation often involves a flexible/unstructured or an
      intrinsically disordered (ID) region of proteins. Structural analyses of the ULK1
      protein suggest that most of its functionally important phosphorylation sites are
      located in an ID region. We propose that this ID nature facilitates AMPK-mediated
      phosphorylation of ULK1, which may provide a mechanism for ULK1 functions in
      response to nutrient deprivation. Understanding how an ID region of ULK1
      modulates its post-translational modifications through AMPK in regulating
      allosteric coupling will significantly help in defining the cellular and
      molecular mechanisms involved in ULK1/AMPK functions and in regulation of
      autophagy.

PMID- 21853164
TI  - Impact of elevated O3 on visible foliar symptom, growth and biomass of Cinnamomum
      camphora seedlings under different nitrogen loads.
AB  - The effects of elevated ozone (O(3)) and enhanced nitrogen (N) on the growth and
      biomass of Cinnamomum camphora, a subtropical evergreen broad-leaved tree
      species, were investigated. The seedlings, supplied with N (NH(4)NO(3) solution)
      at 0, 30 and 60 kg ha(-1) year(-1) (simplified as N0, N30, N60, respectively),
      were exposed to ambient (AA) or elevated O(3) (AA + 60 nmol mol(-1) and AA + 120
      nmol mol(-1), designated as AA + 60 and AA + 120, respectively) for the 2009 and
      2010 growing seasons. Symptomatic leaf percentages were significantly increased
      with O(3) concentration. AA + 120 significantly decreased the mean leaf size and
      chlorophyll content of both 2009- and 2010-emerged leaves, inhibited the growth
      of stem height and basal diameter, and reduced biomass accumulation of all plant
      parts except for leaves. By comparison, only the chlorophyll content of 2009
      emerged leaves and root dry weight were significantly reduced under AA + 60.
      Specific leaf area, total leaf area and foliar biomass were not affected even at
      a higher O(3) level. On the other hand, N loads, especially N60, exerted
      significantly positive effects on all variables except mean leaf size and
      shoot/root ratio. No significant interactions between O(3) and N were detected,
      suggesting that the N supply at <=60 kg ha(-1) year(-1) did not significantly
      modify the response of C. camphora to O(3) in terms of seedling growth and
      biomass accumulation.

PMID- 21853165
TI  - Novel organogelators based on amine-derived hexaazatrinaphthylene.
AB  - Novel C(3)-symmetrical heteroaromatic hexaazatrinaphthylene (HATNA) gelators
      symmetrically end-substituted with pendant aromatic and aliphatic amines were
      synthesized. Some of these pi-conjugated structures induce self-assembly, forming
      fibers able to gelate solvents of different polarity at low wt% as demonstrated
      by spectroscopic and microscopic techniques.

PMID- 21853166
TI  - Influence of the processing conditions and chemical environment on the crystal
      structures and phonon modes of lanthanide orthotantalates.
AB  - Lanthanide orthotantalates RETaO(4) (RE = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho,
      Er, Tm, Yb, and Lu) were synthesized by solid-state reaction in optimized
      conditions of temperature (1300  degrees C) and time (up to 14 h) to yield
      crystalline materials. The crystal structures of the obtained compounds were
      investigated by X-ray diffraction and Raman scattering. All the samples exhibited
      monoclinic structures, but with different arrangements as a function of the ionic
      radius of the rare-earth metal occupying the A-site. For compounds with the
      largest ionic radii (La-Pr), the ceramics crystallized in the monoclinic
      structure, P2(1)/c (C(2h)(5), #14, Z = 4), while the compounds with intermediate
      ionic radii (Nd-Tb) exhibited the fergusonite M-type structure, I2/a (C(2h)(6),
      #15, Z = 4). Samples with the smallest ionic radii (Dy-Lu) presented the
      fergusonite M'-type structure, P2/a (C(2h)(4), #13, Z = 2). These last two groups
      of compounds exhibited phase transitions, which can be related to the processing
      temperature. The compounds belonging to the M-type structure are stable at high
      temperatures, whilst materials belonging to the M'-type structure are stable at
      low temperatures. The results from XRD and Raman scattering allows us to
      understand the differences between these two structures in terms of the
      vibrational-active modes assigned to each space group. Also, the Raman patterns
      in addition to group-theory calculations for this complete lanthanide series were
      reported for the first time. The experimental results are in perfect agreement
      with theoretical calculations: samples with P2(1)/c (#14) structure showed 36
      Raman-active modes, while both I2/a (#15) and P2/a (#13) structures exhibited 18
      Raman modes.

PMID- 21853167
TI  - Polyelectrolyte multilayers generated in a microfluidic device with pH gradients
      direct adhesion and movement of cells.
AB  - In this study, multilayers from polyethylene imine, heparin and chitosan are
      prepared at three different pH values of 5, 7 and 9. Water contact angle and
      quartz microbalance measurements show that resulting multilayers differ in terms
      of wetting behaviour, layer mass and mechanical properties. The multilayer is
      then formed within a gradient generation microfluidic (MUFL) device. Polyethylene
      imine or heparin solutions of pH 5 are introduced into one inlet and the same
      solutions but at pH 9 into another inlet of the MUFL device. The pH gradient
      established during the multilayer formation can be visualized inside the
      microchamber by pH sensitive fluorophores and confocal laser scanning microscopy.
      From this setup it is expected that properties of multilayers displayed at
      distinct pH values can be realised in a gradient manner inside the MUFL device.
      Behaviour of the osteoblast cell line MG-63 seeded and cultured on top of
      multilayers created inside the MUFL device support this hypothesis. It is
      observed that more cells adhere and spread on multilayers build-up at the basic
      side of the MUFL channel, while those cells on top of multilayers built at pH 5
      are fewer and smaller. These results are consistent with the behaviour of MG-63
      cells seeded on multilayers formed at discrete pH values. It is particularly
      interesting to see that cells start to migrate from multilayers built at pH 5 to
      those built at pH 9 during 6 h of culture. Overall, the presented multilayer
      formation setup applying pH gradients leads to surfaces that promote migration of
      cells.

PMID- 21853168
TI  - A composite feed-forward loop I4-FFL involving IHF and Crc stabilizes expression
      of the XylR regulator of Pseudomonas putida mt-2 from growth phase perturbations.
AB  - Genetic networks are typically composed of a series of connected motifs that
      confer specific logic and dynamic properties to the resulting circuits. While
      some feed forward loop (FFL) variants abound in such networks, others (e.g. the
      type-4 incoherent FFL or I4-FFL) are virtually absent from the known regulatory
      devices. We report here that the key node that rules the expression of the m
      xylene biodegradation pathway of the soil bacterium Pseudomonas putida mt-2
      merges opposite physiological effects of the growth phase by means of a
      regulatory device based on the rarely found I4-FFL motif. Specifically, the FFL
      includes the integration host factor (IHF), which both co-activates the master
      P(u) promoter and represses transcription of its cognate regulatory gene xylR at
      the onset of the stationary phase. On the other hand, the catabolite repression
      control (Crc) protein inhibits translation of XylR during exponential growth. By
      computing these two conflicting regulatory actions within a composite I4-FFL
      gate, cells shield the expression of XylR from perturbations caused by the growth
      phase, thereby ensuring a steady supply of the regulator regardless of
      physiological conditions. This device thus endows xylR expression with a degree
      of robustness in respect to the growth phase that could hardly be achieved with
      e.g. a simple constitutive promoter.

PMID- 21853169
TI  - De novo synthesis of deoxy sugar via a Wharton rearrangement.
AB  - A highly divergent synthesis of alpha-fuco-, alpha-6-deoxy-allo-, alpha-6-deoxy
      altro-pyranosides has been achieved. This route utilizes a Wharton rearrangement
      as part of a new post-glycosylation transformation strategy.

PMID- 21853170
TI  - Iron(II) template synthesis of benzannulated triphospha- and triarsamacrocycles.
AB  - Nine-membered 1,4,7-triphospha- and triarsamacrocycles with unsaturated benzo
      backbones have been prepared using the [Cp(R)Fe](+) unit as a template. The
      cyclisation involves the attack of a coordinated phosphide (or arsenide)
      nucleophile at an activated, electrophilic ortho-fluorophenyl substituent on a
      neighbouring pnictide donor. The macrocycle assembly is of the 2 + 1 type where
      two new chelate rings are formed from appropriately derivatised bidentate and
      monodentate phosphines/arsines. Both [(eta(5)-C(5)H(5))Fe](+) and [(eta(5)
      C(5)Me(5))Fe](+) may be employed for the cyclisation with higher yields generally
      being observed with the unsubstituted Cp. All new compounds have been
      characterised by spectroscopic and analytical methods including the single
      crystal X-ray structure determination of [(eta(5)-C(5)H(5))Fe(tribenzo-9aneP(3)
      Ph,Ph(F)(2))](+), 3a, and [(eta(5)-C(5)H(5))Fe(tribenzo-9aneAs(3)
      Ph,Ph(F)(2))](+), 5, as the tetraphenylborate salts. The crystal structures are
      isomorphous and show the unique conformation of these new macrocycles with a 'cup
      shaped' cavity formed by the rigid benzo-backbones. The 9aneAs(3) derivative is
      the first example of a nine-membered triarsamacrocycle.

PMID- 21853171
TI  - Synthesis, characterization and phase transitions of the inorganic-organic
      layered perovskite-type hybrids [(C(n)H(2n+1)NH3)2PbI4], n = 7, 8, 9 and 10.
AB  - Four inorganic-organic hybrid materials that consist of 2-D layers of corner
      sharing lead(II) iodide octahedra separated by alkylammonium chains have been
      crystallized and characterized via single-crystal XRD (SCXRD). The four hybrids,
      represented by the general formula [(C(n)H(2n+1)NH(3))(2)PbI(4)] and abbreviated
      C(n)PbI, exhibit multiple reversible phase transitions for a narrow temperature
      range. The transition temperatures were determined with differential scanning
      calorimetry experiments. The number of transitions and the transition
      temperatures are dependant on the chain length; for n = 7 and 10, there are three
      transitions, and for n = 8 and 9, there are two transitions. Regardless of the
      number of transitions, all four compounds have identical lowest temperature
      phases, which have inorganic layers that are eclipsed, non-planar conformations
      of the alkyl ammonium chains and yellow-coloured crystals. The next highest
      temperature phase for three of the compounds (C(10)PbI goes through an
      intermediate phase first), has staggered inorganic layers, all-trans planar
      conformations of the chains and orange coloured crystals. The highest temperature
      phase for n = 8 and 10 has red-coloured crystals and shows a disordering of the
      alkylammonium chains over two positions and staggered inorganic layers. The high
      temperature phase of C(7)PbI retains its orange colour and has only increased
      thermal motion of its alkylammonium chain. The structure of the high temperature
      phase of C(9)PbI was not determined. The SCXRD structures of the various phases
      give clues to the structural changes that the compounds undergo at the phase
      transitions, which will now enable future studies of their optical and electronic
      properties to be better understood.

PMID- 21853172
TI  - Surface-enhanced Raman scattering sensor for theophylline determination by
      molecular imprinting on silver nanoparticles.
AB  - A surface-enhanced Raman scattering (SERS)-based sensor for the determination of
      theophylline (THO) has been developed by imprinting the target molecules on the
      surface of silver nanoparticles. The desired recognition sites are generated
      after template removal and homogeneous distribution on the silver nanoparticles
      that have been incorporated within polymer matrix by the in situ reduction of
      theophylline-silver complexes, providing molecular recognition ability and SERS
      active surfaces. The theophylline molecules, complementary to the shape, size,
      and functionality of the recognition cavities, can selectively bind to the
      recognition sites at the surface of silver nanoparticles driven by the formation
      of hydrogen bonding and surface coordination. It has been demonstrated that the
      SERS signals of the theophylline molecules captured on the surface of the silver
      nanoparticles have a good reproducibility and a dose-response relationship to the
      target analytes, showing the potential for reliable identification and
      quantification of the bioactive compound. The molecular imprinting-based SERS
      sensor, like antibodies or enzymes, also possesses the ability to distinguish
      theophylline from the closely related structure caffeine due to the variations of
      molecular size and shape as well as the different affinity to silver ions.

PMID- 21853173
TI  - Development and application of an electrochemiluminescent flow-injection cell
      based on CdTe quantum dots modified electrode for high sensitive determination of
      dopamine.
AB  - A nano-liter sized flow-cell is developed for constructing a flow injection
      analysis (FIA) system with electrochemiluminescent (ECL) detection. A sensitive
      ECL electrode is applied as the working electrode in this flow-cell. It is
      obtained by immobilizing the composite of CdTe quantum dots (QDs), carbon
      nanotubes (CNTs) and chitosan (Chit) on indium tin oxide (ITO) glass. The CdTe
      QDs were synthesized in our lab and possessed a high quantum yield. It has been
      demonstrated as an efficient anodic ECL material with the triethylamine (TEA) as
      the co-reactant. The flow-cell gives the stable ECL background under optimized
      conditions for parameters such as electrolytic pulse, concentration of TEA and
      flow rate, etc. The sensitive ECL quenching response of dopamine (DA) is realized
      on this FIA system within the linear range from 10 pM to 4 nM and a detection
      limit as low as 3.6 pM. It is practically used to determine the neurotransmitters
      in cerebro-spinal fluid (CSF) with DA as the index and with an average recovery
      of 94%.

PMID- 21853174
TI  - A phosphoarginine containing peptide as an artificial SH2 ligand.
AB  - We have developed a synthesis of phosphoarginine containing peptides using a
      bis(2,2,2-trichloroethyl) protected phosphoarginine derivative as building block.
      Binding studies and computer modelling demonstrate the ability of the SH2 domain
      from Src kinase to recognize a phosphoarginine-containing peptide in a phosphoryl
      group-dependent manner.

PMID- 21853175
TI  - Facile one-pot synthesis of yolk-shell superparamagnetic nanocomposites via
      ternary phase separations.
AB  - Yolk-shell composites with an Fe(3)O(4)/silica hybrid shell and a polymer core
      are prepared via a facile one-pot and self-template process. Thicknesses of the
      inorganic shell and interior space of the composites are well controlled by
      tuning the ternary phase separations.

PMID- 21853176
TI  - Facile functionalization of a fully fluorescent perfluorophenyl BODIPY:
      photostable thiol and amine conjugates.
AB  - Selective nucleophilic substitution on a perfluorophenyl unit comprising a BODIPY
      fluorophore using an alkanethiol or a primary amine offers a quantitative
      fluorophore labelling strategy, while retaining high photostability and emission
      quantum yields approaching unity.

PMID- 21853177
TI  - Morphology evolution of Cu(2-x)S nanoparticles: from spheres to dodecahedrons.
AB  - An oriented attachment and growth mechanism allows an accurate control of the
      size and morphology of Cu(2-x)S nanocrystals, from spheres and disks to
      tetradecahedrons and dodecahedrons. The synthesis conditions and the growth
      mechanism are detailed here.

PMID- 21853178
TI  - Separation of proteins using supramolecular gel electrophoresis.
AB  - An amphiphilic low-molecular-weight hydrogelator 1 was synthesized. A tris
      glycine-SDS solution gel of 1 was applied for electrophoresis to separate
      proteins. Centrifugation of a mixture of protein and a hydrogel of 1 enabled the
      recovery of protein. Various combinations of proteins were applied for
      supramolecular gel electrophoresis (SUGE), and remarkably poor mobility for small
      proteins (<45 kDa) was found.

PMID- 21853179
TI  - Diffusion of small molecules inside a peptide hydrogel.
AB  - A set of four phenylalanine analogues experiences diffusion retardation when
      transferred from phosphate-buffered saline into a peptide hydrogel of the same pH
      and ionic strength. The extent of retardation increases linearly with logP(oct),
      their lipophilicity.

PMID- 21853180
TI  - Detection of the Pseudomonas Quinolone Signal (PQS) by cyclic voltammetry and
      amperometry using a boron doped diamond electrode.
AB  - 2-Heptyl-3-hydroxy-4-quinolone, known as the Pseudomonas Quinolone Signal, is a
      key regulator of bacterial cooperative behaviour known as quorum sensing. A
      simple electrochemical strategy was employed for its sensitive detection using a
      bare boron-doped diamond electrode by cyclic voltammetry and amperometry. PQS
      (and potentially other quinolones) was then detected in cultures of P. aeruginosa
      pqsL(-) mutant strains.

PMID- 21853181
TI  - Structural characterisation of phosphate materials: new insights into the spatial
      proximities between phosphorus and quadrupolar nuclei using the D-HMQC MAS NMR
      technique.
AB  - We show in this article how the spatial proximity between phosphorus and
      quadrupolar nuclei can be efficiently and easily investigated with the D-HMQC
      (Dipolar Hetero-nuclear Multiple-Quantum Coherences) NMR technique. Compared to
      the commonly used CP-HETCOR (Cross-Polarisation HETero-nuclear CORrelation)
      sequence, the D-HMQC pulse scheme exhibits a higher sensitivity and a better
      robustness with respect to spinning frequency, electronic shielding and
      quadrupole interaction, and thus does not require time-consuming and complicated
      optimisation procedures. The advantages of the D-HMQC are demonstrated in this
      article through the acquisition of (31)P/S through-space two-dimensional
      correlation NMR spectra providing unreported structural information on (i) a
      sodium alumino-silicate glass doped with only 3% of P(2)O(5), (ii) a potassium
      boro-phosphate glass containing BO(3) and BO(4) groups and (iii) a crystalline
      zirconium vanado-phosphate. All these systems, representative of the most
      important mixed phosphate network materials, cannot be correctly investigated
      with the conventional CP-HETCOR NMR technique.

PMID- 21853182
TI  - Molecular spectroscopy for ground-state transfer of ultracold RbCs molecules.
AB  - We perform one- and two-photon high resolution spectroscopy on ultracold samples
      of RbCs Feshbach molecules with the aim to identify a suitable route for
      efficient ground-state transfer in the quantum-gas regime to produce quantum
      gases of dipolar RbCs ground-state molecules. One-photon loss spectroscopy allows
      us to probe deeply bound rovibrational levels of the mixed excited (A(1)Sigma(+)
      b(3)Pi)0(+) molecular states. Two-photon dark state spectroscopy connects the
      initial Feshbach state to the rovibronic ground state. We determine the binding
      energy of the lowest rovibrational level |v'' = 0, J'' = 0> of the X(1)Sigma(+)
      ground state to be D = 3811.5755(16) cm(-1), a 300-fold improvement in accuracy
      with respect to previous data. We are now in the position to perform stimulated
      two-photon Raman transfer to the rovibronic ground state.

PMID- 21853183
TI  - Resonance scattering particles as biological nanosensors in vitro and in vivo.
AB  - Recently dark-field microscopy and Rayleigh scattering spectroscopy have emerged
      as complementary technologies for ultrasensitive biological detection and imaging
      with high spatial and temporal resolution. Plasmonic resonant nanoparticles are
      key nano-scale probes for these technologies that have enabled single-molecule
      sensitivity and imaging. In this tutorial review, we focus on the use of
      plasmonic probes as single-particle biological nanosensors in vitro and in vivo.
      The progress in this field over the last decade will be highlighted.

PMID- 21853184
TI  - Graphene-based semiconductor photocatalysts.
AB  - Graphene, a single layer of graphite, possesses a unique two-dimensional
      structure, high conductivity, superior electron mobility and extremely high
      specific surface area, and can be produced on a large scale at low cost. Thus, it
      has been regarded as an important component for making various functional
      composite materials. Especially, graphene-based semiconductor photocatalysts have
      attracted extensive attention because of their usefulness in environmental and
      energy applications. This critical review summarizes the recent progress in the
      design and fabrication of graphene-based semiconductor photocatalysts via various
      strategies including in situ growth, solution mixing, hydrothermal and/or
      solvothermal methods. Furthermore, the photocatalytic properties of the resulting
      graphene-based composite systems are also discussed in relation to the
      environmental and energy applications such as photocatalytic degradation of
      pollutants, photocatalytic hydrogen generation and photocatalytic disinfection.
      This critical review ends with a summary and some perspectives on the challenges
      and new directions in this emerging area of research (158 references).

PMID- 21853185
TI  - Development of homogeneous and heterogenized rhodium(I) and palladium(II)
      complexes with ligands based on a chiral proton sponge building block and their
      application as catalysts.
AB  - Chiral compounds prepared from proton sponge building block 8-((2R,5R)-2,5
      dimethylpyrrolidin-1-yl)naphthalen-1-amine were found to be effective chiral
      ligands for obtaining complexes of rhodium(I) and palladium(II) by reaction with
      [RhCl(cod)](2), PdCl(2)(cod) or Pd(OAc)(2). The complexes bearing triethoxysilane
      groups were immobilized on mesoporous MCM-41 in order to obtain new heterogeneous
      catalysts. Both materials are active in the hydrogenation of alkenes and could be
      recycled without loss of activity or enantioselectivity.

PMID- 21853186
TI  - Synthesis, characterization, and single-molecule metamagnetism of new Co(II)
      polynuclear complexes of pyridine-2-ylmethanol.
AB  - The reaction between pyridine-2-ylmethanol (HL), anhydrous CoCl(2) and NaH
      afforded polynuclear Co(II) complexes [Co(7)(L)(12)]Cl(2) (1), [Co(6)Na(L)(12)]Cl
      (2) and [Co(4)Cl(2)(L)(6)] (3), depending on the HL:CoCl(2) ratio set in the
      reaction. The core structures of the centrosymmetric complexes 1 and 2 are of the
      M@Co(6) type (M = Co or Na, respectively) with a coplanar arrangement of the
      metals whereas that of centrosymmetric 3 is of an incomplete dicubane type. The
      experimental conditions allowing interconversions between these polynuclear
      complexes have been determined, which provides a more rational control of their
      synthesis. Thus, 1 transforms to 3 when reacted with CoCl(2) in a 1 : 1 ratio,
      whereas the same reaction performed with a large excess of CoCl(2) gave the
      tetranuclear pseudo-cubane complex [Co(4)(L)(4)Cl(2)(MeOH)(4)] upon
      recrystallization. Conversely, 1 was isolated from the reaction of 3 with HL and
      NaH. The crystal structure of these compounds is reported, along with the
      magnetic behaviour of 1 and 3. The analysis of the magnetism using the effective
      spin-1/2 Hamiltonian approach revealed single-molecule metamagnetic behavior in
      3.

PMID- 21853187
TI  - Trinuclear ruthenium dendrons based on bridging PHEHAT and TPAC ligands.
AB  - Novel polynuclear compounds, the trinuclear precursor complex cis
      {[(phen)(2)Ru(PHEHAT)](2)Ru(CH(3)CN)(2)}(6+) 4 and the trinuclear TPAC
      (tetrapyrido[3,2-a:2',3'-c:3'',2'-h:2''',3'''-j]acridine) complex
      {[(phen)(2)Ru(PHEHAT)](2)Ru(TPAC)}(6+) 5 have been prepared. Their
      electrochemistry and photophysics indicate that the (3)MLCT (metal to ligand
      charge transfer) emissions involve the external {Ru(PHEHAT)} moieties for both
      complexes and there is no spectro-electrochemical correlation. The trinuclear
      dendron with the TPAC ligand represents a key compound for future constructions
      of much larger species thanks to the TPAC that could bridge another polynuclear
      precursor. For decreasing the length of preparation of these compounds, microwave
      assisted syntheses have been tested and used not only for the targeted complexes
      but also for the precursors ((phen)(2)RuCl(2), {(phen)(2)Ru(phendione)}(2+),
      {(phen)(2)Ru(PHEHAT)}(2+) (PHEHAT = 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12
      hexaazatriphenylene), (DMSO)(4)RuCl(2)), and for the bridging TPAC ligand itself.
      The microwave method allows a drastic decrease of the preparation times,
      especially in the case of the TPAC, from 8 days to 60 min.

PMID- 21853188
TI  - New 2,3-disubstituted-5-hydroxyquinoxaline ligands and their coordination
      chemistry with cyclometallated iridium(III): syntheses, structures and tunable
      electronic properties.
AB  - A new series of para-substituted 2,3-diphenyl-5-hydroxyquinoxaline ligands
      (LH(n)) were synthesised and characterised. These ligands were prepared in high
      yield via a two-step synthetic method. Four novel heteroleptic iridium(III)
      complexes were correspondingly prepared in high yield giving [Ir(ppy)(2)(L(n))].
      Two X-ray crystallographic studies were undertaken on LH(3) and
      [Ir(ppy)(2)(L(2))] with each confirming the proposed formulations, with the
      complex showing the O,N-coordination mode of the quinoxalinato ligand. Density
      functional theoretical calculations were performed, firstly to compare the
      coordinated quinoxalinato system with the related quinolinato analogue, and
      secondly to probe the influence of the variation in para-substitution on the
      ancillary ligand. The calculations suggest that for either the quinoline or
      quinoxaline systems ligand-centred character appears to dominate the HOMO and
      LUMOs. Experimental electrochemical and spectroscopic characterisation showed
      that the subtle variations in absorption and emission wavelengths are probably
      due to ligand-dominated transitions that are influenced by the electronic nature
      of the para-substituted phenyl units in coordinated L(n).

PMID- 21853189
TI  - Interaction of Zn(II) with quinolone drugs: structure and biological evaluation.
AB  - Zinc complexes with the third-generation quinolone antibacterial drugs
      levofloxacin and sparfloxacin have been synthesized and characterized. The
      deprotonated quinolones act as bidentate ligands coordinated to zinc ion through
      the pyridone and a carboxylato oxygen atom. The crystal structures of
      [bis(aqua)bis(levofloxacinato)zinc(II)], 1, and [bis(sparfloxacinato)(1,10
      phenanthroline)zinc(II)], 3, have been determined by X-ray crystallography. The
      biological activity of the complexes has been evaluated by examining their
      ability to bind to calf-thymus DNA (CT DNA) by UV spectroscopy and viscosity
      measurements. UV studies of the interaction of the complexes with DNA have
      revealed that they can bind to CT DNA probably by the intercalative binding mode
      which has also been verified by DNA solution viscosity measurements. The DNA
      binding constants have been also calculated. A competitive study with ethidium
      bromide (EB) showed that the complexes exhibit the ability to displace the DNA
      bound EB indicating that they bind to DNA in strong competition with EB for the
      intercalative binding site. The interaction of the complexes with human and
      bovine serum albumin proteins has been studied by fluorescence spectroscopy
      showing that the complexes exhibit good binding propensity to these proteins
      having relatively high binding constant values. The biological properties of the
      complexes have been evaluated in comparison to the previously reported Zn(II)
      complexes with the first- and second-generation quinolones oxolinic acid and
      enrofloxacin.

PMID- 21853190
TI  - Organometallic reactivity: the role of metal-ligand bond energies from a
      computational perspective.
AB  - The association and dissociation of ligands plays a vital role in determining the
      reactivity of organometallic catalysts. Computational studies with density
      functional theory often fail to reproduce experimental metal-ligand bond
      energies, but recently functionals which better capture dispersion effects have
      been developed. Here we explore their application and discuss future challenges
      for computational studies of organometallic catalysis.

PMID- 21853191
TI  - New half sandwich-type Ru(II) coordination compounds characterized by the fac
      Ru(dmso-S)3 fragment: influence of the face-capping group on the chemical
      behavior and in vitro anticancer activity.
AB  - The Ru(II) complex fac-[RuCl(dmso-S)(3)(dmso-O)(2)][PF(6)] (P2) was found to be
      an excellent precursor for the facile preparation in high yield of half sandwich
      type compounds of the general formula fac-[RuCl(dmso-S)(3)(N)(2)][PF(6)] (e.g.
      (N)(2) = 1,2-diaminoethane (en, 4), trans-1,2-diaminocyclohexane (dach, 5), or 2
      NH(3) (6)). Neutral half sandwich-type compounds of the general formula fac
      [RuCl(dmso-S)(3)(N-O)] where N-O is an anionic chelating ligand (e.g. N-O =
      picolinate (pic, 7)) are best prepared from the universal Ru(II)-dmso precursor
      cis-[RuCl(2)(dmso)(4)] (P1). These complexes, that were fully characterized in
      solution and in the solid state, are structurally similar to the anticancer
      organometallic compounds [Ru(eta(6)-arene)(chel)Cl][PF(6)](n) but, in place of a
      face-capping arene, have the fac-Ru(dmso-S)(3) fragment. In contrast to what
      observed for the corresponding arene compounds, that rapidly hydrolyze the Cl
      ligand upon dissolution in water, compounds 4-6 are very stable and inert in
      aqueous solution. Probably their inertness is the reason why they showed no
      significant cytotoxicity against the MDA-MB-231 cancer cell line.

PMID- 21853192
TI  - SU8 diaphragm micropump with monolithically integrated cantilever check valves.
AB  - This paper presents a SU8 unidirectional diaphragm micropump with embedded out-of
      plane cantilever check valves. The device represents a reliable and low-cost
      solution for integration of microfluidic control in lab-on-a-chip devices. Its
      planar architecture allows monolithic definition of its components in a single
      step and potential integration with previously reported PCR, electrophoresis and
      flow-sensing SU8 microdevices. Pneumatic actuation is applied on a PDMS
      diaphragm, which is bonded to the SU8 body at wafer level, further enhancing its
      integration and mass production capabilities. The cantilever check valves move
      synchronously with the diaphragm, feature fast response (10ms), low dead volume
      (86nl) and a 94% flow blockage up to 300kPa. The micropump achieves a maximum
      flow rate of 177 MUl min(-1) at 6 Hz and 200 kPa with an effective area of 10
      mm(2). The device is reliable, self-priming and tolerant to particles and big
      bubbles. To the knowledge of the authors, this is the first micropump in SU8 with
      monolithically integrated cantilever check valves.

PMID- 21853193
TI  - Integrated sieving microstructures on microchannels for biological cell trapping
      and droplet formation.
AB  - We have developed a single step microfabrication method to prepare constriction
      microstructures on a PCB master by controlling the etching time of two
      microchannels separated by a finite distance that is easily attainable using
      imagesetters widely available in the printing industry. PDMS replica of the
      constriction structures present sieving microstructures (microsieves) that could
      be used for size-dependent trapping of microspheres, biological cells and the
      formation of water-in-oil droplets.

PMID- 21853194
TI  - Cell receptor and surface ligand density effects on dynamic states of adhering
      circulating tumor cells.
AB  - Dynamic states of cancer cells moving under shear flow in an antibody
      functionalized microchannel are investigated experimentally and theoretically.
      The cell motion is analyzed with the aid of a simplified physical model featuring
      a receptor-coated rigid sphere moving above a solid surface with immobilized
      ligands. The motion of the sphere is described by the Langevin equation
      accounting for the hydrodynamic loadings, gravitational force, receptor-ligand
      bindings, and thermal fluctuations; the receptor-ligand bonds are modeled as
      linear springs. Depending on the applied shear flow rate, three dynamic states of
      cell motion have been identified: (i) free motion, (ii) rolling adhesion, and
      (iii) firm adhesion. Of particular interest is the fraction of captured
      circulating tumor cells, defined as the capture ratio, via specific receptor
      ligand bonds. The cell capture ratio decreases with increasing shear flow rate
      with a characteristic rate. Based on both experimental and theoretical results,
      the characteristic flow rate increases monotonically with increasing either cell
      receptor or surface-ligand density within certain ranges. Utilizing it as a
      scaling parameter, flow-rate dependent capture ratios for various cell-surface
      combinations collapse onto a single curve described by an exponential formula.

PMID- 21853195
TI  - Proteomic analysis of the Mexican lime tree response to "Candidatus Phytoplasma
      aurantifolia" infection.
AB  - "Candidatus Phytoplasma aurantifolia" is the causative agent of witches' broom
      disease in the Mexican lime tree (Citrus aurantifolia L.), and is responsible for
      major tree losses in Southern Iran and Oman. The pathogen is strictly biotrophic,
      and, therefore, completely dependent on living host cells for its survival. The
      molecular basis of compatibility and disease development in this system is poorly
      understood. We applied a proteomics approach to analyse gene expression in
      Mexican limes infected with "Ca. Phytoplasma aurantifolia". Leaf samples were
      collected from healthy and infected plants and were analysed using 2-DE coupled
      with MS. Among 800 leaf proteins that were detected reproducibly in eight
      biological replicates of healthy and eight biological replicates of infected
      plants, 55 showed a significant response to the disease. MS resulted in
      identification of 39 regulated proteins, which included proteins that were
      involved in oxidative stress defence, photosynthesis, metabolism, and the stress
      response. Our results provide the first proteomic view of the molecular basis of
      the infection process and identify genes that could help inhibit the effects of
      the pathogen.

PMID- 21853196
TI  - Nafion coating the ferrocenylalkanethiol and encapsulated glucose oxidase
      electrode for amperometric glucose detection.
AB  - This paper describes the fabrication and application of a complex electrode-
      Nafion film coating ferrocenylalkanethiol (FcC(11)SH) and encapsulated glucose
      oxidase (GOD) on a gold electrode. FcC(11)SH is employed as a mediator enabling
      the electron transfer between GOD and the electrode, GOD is encapsulated in
      polyacrylamide gel to improve the stability of the enzyme, and the Nafion film is
      coated on the modified electrode to eliminate interferents such as ascorbic acid,
      uric acid and acetaminophen in amperometric glucose detection. It is noticed that
      such a complex electrode exhibits excellent catalytic activity for glucose
      oxidation, and preserves the native structure of GOD and therefore its enzymatic
      activity. The encapsulated GOD retains more than 80% of its original biocatalytic
      activity even after 24 days, much longer than that of naked GOD molecules
      attached directly to the electrode. The oxidation peak current at the modified
      electrode shows a linear relationship with the glucose concentration in the range
      from 0.05 to 20 mM with a detection limit of 2.4 MUM. In addition, the electrode
      displays a rapid response and good reproducibility for glucose detection, and has
      been successfully employed for glucose detection in blood plasma samples.

PMID- 21853197
TI  - Using boronolectin in MALDI-MS imaging for the histological analysis of cancer
      tissue expressing the sialyl Lewis X antigen.
AB  - Certain carbohydrate-based biomarkers are known to correlate with cancer
      formation and progression. By targeting sialyl Lewis X, we have developed the
      first boronolectin-MS tag conjugate, which allows for MALDI-based imaging of
      cancer based on its cell surface carbohydrate.

PMID- 21853199
TI  - Self-assembly of D-penicillaminato M6M'8 (M = Ni(II), Pd(II), Pt(II); M' = Cu(I),
      Ag(I)) clusters and their organization into extended La(III)M6M'8 supramolecular
      structures.
AB  - A series of chiral M(6)M'(8) cluster compounds having twelve free carboxylate
      groups, [M(6)M'(8)(D-pen-N,S)(12)X](5-) (M/M'/X = Pd(II)/Ag(I)/Cl(-) ([1](5-)),
      Pd(II)/Ag(I)/Br(-) ([2](5-)), Pd(II)/Ag(I)/I(-) ([3](5-)), Ni(II)/Ag(I)/Cl(-)
      ([4](5-)), Pt(II)/Ag(I)/Cl(-) ([5](5-)), Pd(II)/Cu(I)/Cl(-) ([6](5-)); D-H(2)pen
      = D-penicillamine), in which six cis-[M(D-pen-N,S)(2)](2-) square-planar units
      are bound to a [M'(8)X](7+) cubic core through sulfur-bridges, was synthesized by
      the reactions of cis-[M(D-pen-N,S)(2)](2-) with M' in water in the presence of
      halide ions. These M(6)M'(8) clusters readily reacted with La(3+) in aqueous
      buffer to form La(III)(2)M(6)M'(8) heterotrimetallic compounds,
      La(2)[1](CH(3)COO), La(2)[2](CH(3)COO), La(2)[3](CH(3)COO), La(2)[4](CH(3)COO),
      La(2)[5](CH(3)COO) and La(2)[6]Cl, in which the M(6)M'(8) cluster units are
      linked by La(3+) ions through carboxylate groups in a 1 : 2 ratio. While the
      La(III)(2)M(6)Ag(I)(8) compounds derived from [1](5-), [2](5-), [3](5-), [4](5-)
      and [5](5-) have a 1D helix supramolecular structure with a right-handedness, the
      La(III)(2)Pd(II)(6)Cu(I)(8) compound derived from [6](5-) has a 2D sheet-like
      structure with a triangular grid of the Pd(II)(6)Cu(I)(8) cluster units. When
      aqueous HCl was added to the reaction solution of [6](5-) and La(3+), another
      La(III)(2)Pd(II)(6)Cu(I)(8) heterotrimetallic compound, La(2)[6]Cl.HCl, in which
      the Pd(II)(6)Cu(I)(8) cluster units are linked by La(3+) ions to form a 2D
      structure with a rectangular grid, was produced. The solid-state structures of
      these La(III)(2)M(6)M'(8) compounds, determined by single-crystal X-ray
      crystallography, along with the spectroscopic properties of the M(6)M'(8) cluster
      compounds in solution, are described.

PMID- 21853198
TI  - Imidazole-modified porphyrin as a pH-responsive sensitizer for cancer
      photodynamic therapy.
AB  - 5,10,15,20-Tetrakis(N-(2-(1H-imidazol-4-yl)ethyl)benzamide)porphyrin produced
      twice as many singlet oxygen ((1)O(2)) molecules at pH 5.0 (quantum yield 0.53 +/
      0.01) than at pH 7.4, whereas the (1)O(2) quenching rate was reduced by a factor
      of 2.5 for a pH change from 7.4 to 5.0.

PMID- 21853200
TI  - Synthesis, characterization and catalytic activity of magnesium and zinc
      aminophenoxide complexes: catalysts for ring-opening polymerization of L-lactide.
AB  - A series of novel magnesium and zinc aminophenoxide complexes were successfully
      synthesized and one zinc complex was characterized by X-ray crystallography. They
      were also investigated as initiators for the ring opening polymerization of L
      lactide. The complexes are effective in forming polylactides with good
      conversions. The nature and steric bulk of the ligands coordinated to the central
      metal ions enormously influenced the polymer properties. Among all the complexes,
      the zinc aminophenoxide complexes as initiators produced polymers with good
      molecular weight control and relatively narrow PDIs.

PMID- 21853201
TI  - Efficient biotinylation of methacryloyl-functionalized nonadherent cells for
      formation of cell microarrays.
AB  - In order to obtain cell microarrays formed with human promyelocytic leukemia
      cells (HL-60), biotinylation of methacryloyl-functionalized HL-60 cells was
      performed via a thiol-ene reaction with thiol-terminated 4-arm poly(ethylene
      glycol) (PEG(4)10K-SH). Biotinylated HL-60 cells were selectively adhered onto an
      avidin-patterned surface with high viability.

PMID- 21853202
TI  - Carbon nitride polymer sensitized TiO2 nanotube arrays with enhanced visible
      light photoelectrochemical and photocatalytic performance.
AB  - Novel carbon nitride polymer sensitized TiO(2) nanotube arrays with high
      photocatalytic activity and photoelectrochemical response under visible light
      irradiation are prepared by electrodeposition.

PMID- 21853203
TI  - Flame synthesis of hierarchical nanotubular rutile titania derived from natural
      cellulose substance.
AB  - Hierarchical nanotubular rutile titania material was fabricated by facile flame
      burning of ultrathin titania gel film coated cellulose nanofibres of commercial
      cellulose substance (filter paper), which possesses efficient photocatalytic
      performance for degradation of organic dye (methylene blue) under ultraviolet
      irradiation.

PMID- 21853204
TI  - Caspase-3 controlled assembly of nanoparticles for fluorescence turn on.
AB  - A caspase-3 controlled condensation was applied to self-assemble biotinylated
      nanoparticles for capturing FITC-labelled streptavidin and subsequently turning
      on the fluorescence signal.

PMID- 21853205
TI  - Cyclopalladated complexes of 4-aryl-2,1,3-benzothiadiazoles: new emitters in
      solution at room temperature.
AB  - The cyclopalladation of the 4-aryl-2,1,3-benzothiadiazoles 1a-c with palladium
      acetate in acetic acid afforded the novel dimeric complexes 2a-c in good yields.
      These were then converted into the monomeric pyridine-, chloro-coordinated
      cyclometallated complexes 3a-c through reaction with lithium chloride in acetone
      and then pyridine in dichloromethane. All complexes were fully characterized by
      means of NMR, IR and elemental analysis. The X-ray structure of complex 2c
      revealed that it presents transoid geometry, whereas the X-ray structure of 3c
      shows that the pyridine ligand and the thiazole ring are mutually trans.
      Photophysical properties were investigated by means of UV-Vis absorption and
      fluorescence emission in solution. Solid-state diffuse reflectance UV-Vis spectra
      (DRUV) were also applied in order to better characterize the complexes
      photophysics in the solid state. All complexes present intense absorption at
      around 300 nm (lambda(1)) via(1)LC transitions located in BTD ligands, and
      additional low energy absorption bands, higher than 450 nm (lambda(2)) of (1)MLCT
      character. The complexes are fluorescent in solution at room temperature, where
      two emission bands could be observed, a high energy band (excitation @ lambda(1))
      ascribed to the ligand emission and an additional red shifted low intense band
      (excitation @ lambda(2)) due to the complex emission.

PMID- 21853206
TI  - Does DFT-D estimate accurate energies for the binding of ligands to metal
      complexes?
AB  - We have studied the homolytic dissociation of a methyl radical from a model of
      methyl cobalamin. For this reaction, density functional theory with an atom
      pairwise dispersion correction (DFT-D) gives a dispersion contribution to the
      bond dissociation energy (BDE) of 22-51 kJ mol(-1) depending on the functional,
      i.e. much more than common estimates for the total dispersion interaction energy
      of the methyl group in typical solvents. We show that this large energy
      correction results from many rather small (0-2 kJ mol(-1)) interactions that
      arise between the ligand and the metal and the other ligands when a short metal
      ligand bond is formed. The energy terms result mostly from atom pairs connected
      by two or three bonds, i.e. terms that normally are ignored or scaled down at the
      molecular mechanics level, and have large contributions from r(-8) terms. The
      added dispersion energy diminishes the variation in the calculated BDE observed
      among various generalised-gradient approximation (GGA) functionals, whereas a gap
      still persists between the results of GGA and hybrid functionals. Model
      calculations at the local MP2 and CCSD (second-order perturbation theory and
      coupled cluster theory with single and double excitations) levels are in a
      similar range as the dispersion interactions estimated by DFT-D (23-29 kJ mol(
      1)). However, both the DFT-D and the wavefunction-based results include middle
      range correlation effects that vary greatly between different DFT methods owing
      to their different density-based description in the short-range regime.
      Therefore, it is not meaningful to discuss which DFT method gives the most
      accurate estimate of the dispersion contribution to the BDE. Moreover, for a
      balanced treatment of dispersion during the binding reaction in solution, the
      dispersion energy of the ligand and the unbound complex with the surroundings
      needs also to be considered, which decreases the net dispersion contribution to
      binding by ~20 kJ mol(-1).

PMID- 21853207
TI  - Highly selective SERS probe for Hg(II) detection using tryptophan-protected
      popcorn shaped gold nanoparticles.
AB  - Contamination of the environment with toxic Hg(II) is becoming a huge concern
      throughout the world now. Driven by the need, this communication reports for the
      first time a tryptophan protected popcorn shaped gold nanomaterials based SERS
      probe for rapid, easy and highly selective recognition of Hg(II) ions in the 5
      ppb level from aqueous solution, with high sensitivity and selectivity over
      competing analytes. We demonstrate that our SERS assay is capable of measuring
      the amount of Hg(II) in alkaline battery.

PMID- 21853208
TI  - Reactions of dehydrodiferulates with ammonia.
AB  - Lignocellulosic materials derived from forages and agricultural residues are
      potential sustainable resources for production of bioethanol or other liquid
      biofuels. However, the natural recalcitrance of such materials to enzymatic
      hydrolysis is a major obstacle in their efficient utilization. In grasses, much
      of the recalcitrance is associated with ferulate cross-linking in the cell wall,
      i.e., with polysaccharide-polysaccharide cross-linking that results from ferulate
      dehydrodimerization or with lignin-polysaccharide cross-linking that results from
      the incorporation of (polysaccharide-bound) ferulates or diferulates into lignin,
      mainly via free-radical coupling reactions. Many pretreatment methods have been
      developed to address recalcitrance, with ammonia pretreatments in general, and
      the AFEX (Ammonia Fiber Expansion) process in particular, among the more
      promising methods. In order to understand the polysaccharide liberating reactions
      involved in the cleavage of diferulate cell wall cross-links during AFEX
      pretreatment, reaction products from five esters modeling the major diferulates
      in grass cell walls treated under AFEX-like conditions were separated and
      characterized by NMR and HR-MS. Results from this study indicate that, beyond the
      anticipated amide products, a range of degradation products derive from an array
      of cleavage and substitution reactions, and reveal various pathways for
      incorporating ammonia-based nitrogen into biomass.

PMID- 21853209
TI  - One pot synthesis of cis-bispyrimidodiazepinone derivatives via low-valent
      titanium reagent (TiCl4/Sm).
AB  - An efficient and convenient method for the preparation of cis
      bispyrimidodiazepinone derivatives has been described. A variety of substrates
      can participate in the process with good yields, making this methodology suitable
      for library synthesis in drug discovery efforts. The mechanistic course of the
      reaction suggests the involvement of reduction, coupling which determine the
      products' configuration and cyclization by one-pot.

PMID- 21853210
TI  - First principles scheme to evaluate band edge positions in potential transition
      metal oxide photocatalysts and photoelectrodes.
AB  - The positions of electronic band edges are one important metric for determining a
      material's capability to function in a solar energy conversion device that
      produces fuels from sunlight. In particular, the position of the valence band
      maximum (conduction band minimum) must lie lower (higher) in energy than the
      oxidation (reduction) reaction free energy in order for these reactions to be
      thermodynamically favorable. We present first principles quantum mechanics
      calculations of the band edge positions in five transition metal oxides and
      discuss the feasibility of using these materials in photoelectrochemical cells
      that produce fuels, including hydrogen, methane, methanol, and formic acid. The
      band gap center is determined within the framework of DFT+U theory. The valence
      band maximum (conduction band minimum) is found by subtracting (adding) half of
      the quasiparticle gap obtained from a non-self-consistent GW calculation. The
      calculations are validated against experimental data where possible; results for
      several materials including manganese(ii) oxide, iron(ii) oxide, iron(iii) oxide,
      copper(i) oxide and nickel(ii) oxide are presented.

PMID- 21853211
TI  - Molecular-shape selectivity by molecular gel-forming compounds: bioactive and
      shape-constrained isomers through the integration and orientation of weak
      interaction sites.
AB  - A molecular gel system was assembled on carrier particles and the integrated
      effect of weak interaction sites enabled highly efficient separation of the
      bioactive and shape-constrained isomers of tocopherols, beta-carotene, and
      polycyclic aromatic hydrocarbons (PAHs) by multiple interaction mechanisms.

PMID- 21853212
TI  - Hierarchical protonated titanate nanostructures for lithium-ion batteries.
AB  - 3D protonated titanate nanoflowers synthesized by an organic-free and cost
      effective facile method exhibit a high reversible capacity, excellent cycling
      performance, and a remarkable rate capability when they worked as anode electrode
      materials for lithium-ion batteries.

PMID- 21853213
TI  - Facile synthesis of NiAl-layered double hydroxide/graphene hybrid with enhanced
      electrochemical properties for detection of dopamine.
AB  - Layered double hydroxides (LDHs), also known as hydrotalcite-like anionic clays,
      have been investigated widely as promising electrochemical active materials. Due
      to the inherently weak conductivity, the electrochemical properties of LDHs were
      improved typically by utilization of either functional molecules intercalated
      between LDH interlayer galleries, or proteins confined between exfoliated LDH
      nanosheets. Here, we report a facile protocol to prepare NiAl-LDH/graphene (NiAl
      LDH/G) nanocomposites using a conventional coprecipitation process under low
      temperature conditions and subsequent reduction of the supporting graphene oxide.
      Electrochemical tests showed that the NiAl-LDH/G modified electrode exhibited
      highly enhanced electrochemical performance of dopamine electrooxidation in
      comparison with the pristine NiAl-LDH modified electrode. Results of high
      resolution transmission electron microscopy and Raman spectra provide convincing
      information on the nanostructure and composition underlying the enhancement. Our
      results of the NiAl-LDH/G modified electrodes with the enhanced electrochemical
      performance may allow designing a variety of promising hybrid sensors via a
      simple and feasible approach.

PMID- 21853215
TI  - Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal
      relaxivity for targeted cancer imaging.
AB  - We report the development of a novel magnetic nano-contrast agent (nano-CA) based
      on Gd(3+) doped amorphous TiO(2) of size ~25 nm, exhibiting enhanced longitudinal
      relaxivity (r(1)) and magnetic resonance (MR) contrasting together with excellent
      biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T
      clinical MR imaging system revealed that the amorphous phase of doped titania has
      the highest r(1) relaxivity which is ~2.5 fold higher than the commercially used
      CA MagnevistTM. The crystalline (anatase) samples formed by air annealing at 250 
      degrees C and 500  degrees C showed significant reduction in r(1) values and MR
      contrast, which is attributed to the loss of proton-exchange contribution from
      the adsorbed water and atomic re-arrangement of Gd(3+) ions in the crystalline
      host lattice. Nanotoxicity studies including cell viability, plasma membrane
      integrity, reactive oxygen stress and expression of pro-inflammatory cytokines,
      performed on human primary endothelial cells (HUVEC), human blood derived
      peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma
      (KB) cell line showed excellent biocompatibility up to relatively higher doses of
      200 MUg ml(-1). The potential of this nano-CA to cause hemolysis, platelet
      aggregation and plasma coagulation were studied using human peripheral blood
      samples and found no adverse effects, illustrating the possibility of the safe
      intravenous administration of these agents for human applications. Furthermore,
      the ability of these agents to specifically detect cancer cells by targeting
      molecular receptors on the cell membrane was demonstrated on folate receptor (FR)
      positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA
      showed receptor specific accumulation on cell membrane while leaving the normal
      fibroblast cells (L929) unstained. This study reveals that the Gd(3+) doped
      amorphous TiO(2) nanoparticles having enhanced magnetic resonance contrast and
      high biocompatibility is a promising candidate for molecular receptor targeted MR
      imaging.

PMID- 21853216
TI  - [Black spots in the eye].
AB  - Senile scleral plaques are characterized by a calcification located at the
      insertion of the horizontal rectus muscles. As a possible cause for their
      development a combination of solar tissue damage and continuous mechanical stress
      is discussed. We present a case of a 76-year-old male whose wife noticed
      expulsion of a calcified scleral plaque while applying antiglaucoma eyedrops. The
      local antiglaucoma therapy was stopped and acetacolamide was administered. Local
      therapy consisted of hyaluronic acid eyedrop and calcium pantothenate and retinol
      palmiate eye ointment. This treatment led to a rapid reepithelialization. The
      expulsion of calcified senile scleral plaques is a described complication which
      can necessitate surgical treatment.

PMID- 21853217
TI  - [Influence of different multifocal intraocular lens concepts on retinal stray
      light parameters].
AB  - PURPOSE: Multifocal intraocular lenses (MIOL) are known to induce various photic
      phenomena depending on the optical principle. The aim of this study was to
      investigate the correlation between stray light measurements performed with the C
      Quant (Oculus, Germany) and the results of a subjective patient questionnaire.
      PATIENTS AND METHODS: In this study three different MIOLs were compared: AMO
      ReZoom (refractive design, n=10), AMO ZM900 (diffractive design, n=10) and
      Oculentis Mplus (near segment design, n=10). Cataract and refractive patients
      were enrolled in the study. Functional results were evaluated at least 3 months
      postoperatively followed by stray light measurements and a subjective
      questionnaire. RESULTS: Surgery was performed for all patients without
      complications. The three groups were matched for age, IOL power and corrected
      distance visual acuity (CDVA). Significantly different stray light (median)
      values log(s) were found (Kruskal-Wallis test, p<0.05): 1.12 log (refractive),
      1.13 log (segment) and 1.28 log (diffractive). The subjective questionnaire did
      not show differences in glare perception but refractive MIOL patients noticed
      more halos surrounding light sources than the diffractive and segment MIOL
      patients. CONCLUSIONS: Stray light and subjective photopic phenomena do not show
      any basic correlation. Measurements in patients with refractive MIOLs showed less
      stray light than near segment or diffractive MIOLs. However, refractive MIOLs
      induced more halos compared to the other groups analyzed.

PMID- 21853218
TI  - [Paecilomyces lilacinus keratitis].
AB  - Paecilomyces lilacinus is a rare cause of contact lens-associated keratitis. The
      infection is difficult to eradicate because of multiple antifungal drug
      resistance and has a poor outcome. A female patient developed contact lens
      associated keratitis and Paecilomyces lilacinus could be demonstrated in the
      corneal abrasion. Despite antifungal therapy with voriconazole a keratoplasty a
      chaud was necessary and a poor final visual acuity could not be avoided.

PMID- 21853219
TI  - [Eye irritation and chemical eye burns. Review of experimental and clinical
      studies].
AB  - Chemical burns of the eye are becoming rare due to improvements in occupational
      protection. Effective decontamination is the foundation for good clinical results
      of this ophthalmological emergency. The toxicological aspect focuses on
      classifying the specific toxicity of a chemical substance by evaluating the
      degree of eye irritation and eye burns. Chemical substances are classified into
      defined risk levels by specific tests. The traditional ophthalmological approach
      is based on the clinical presentation of eye burns as a result of contact with a
      specific toxic substance. In an integral approach it is shown that substance
      specific characteristics, such as concentration and specific reactivity as well
      as individual features, such as mode and duration of exposition have an influence
      on the clinical appearance of the tissue damage. The decontamination is dependent
      on the mode of action and the effectiveness of the decontamination solution.
      Amphoteric substances have the best effectiveness for decontamination of the eye
      due to their specific characteristics.

PMID- 21853223
TI  - Further studies on mefloquine and praziquantel alone or interaction of both drugs
      against Schistosoma japonicum in vitro.
AB  - The aim of the present study is to further understand and analyze the interaction
      of mefloquine with praziquantel against adult Schistosoma japonicum in vitro.
      Mice infected with S. japonicum cercariae for 35-37 days were sacrificed, and
      adult schistosomes were collected by perfusion. Schistosomes were placed to each
      of 12 wells of a Falcon plate and maintained in RPMI 1640 supplemented by 10%
      calf serum. For determination of 50% and 95% lethal concentration (LC50 and LC95)
      of the two drugs in vitro, schistosomes were exposed to mefloquine at
      concentrations of 1, 2, 3, 4, 5, 6, 7, and 10 MUg/mL or praziquantel at
      concentrations of 0.001, 0.01, 0.05, 0.1, 0.2, 0.5, 1, 10, and 30 MUg/mL. The
      plate was incubated at 37 degrees C in 95% air + 5% CO2 for 72 h. According to
      the half-life of oral mefloquine and praziquantel in mice, mefloquine combined
      with praziquantel simultaneously, mefloquine administered within 1 h after
      praziquantel and praziquantel administered within 17 h after mefloquine were used
      to evaluate the effect of mefloquine in combination with praziquantel against S.
      japonicum in vitro. The results showed that the LC50 and LC95 of mefloquine
      calculated by the Bliss method were 6.17 MUg/mL (95% confidence limits, 5.84
      6.517 MUg/mL) and 8.703 MUg/mL (95% confidence limits, 7.632-9.797 MUg/mL),
      respectively. As to praziquantel, no worm death was seen when schistosomes were
      exposed to praziquantel at concentrations of 0.005-0.2 MUg/mL for 72 h. While in
      the worms exposed to praziquantel 1, 10, and 30 MUg/mL, strong spasmodic
      contractions of the worm body and vesiculation along the worm surface were
      observed, but 48-75% of the schistosomes survived the exposure in 72-h
      incubation. Meanwhile, the number of dead worms that emerged in each group was
      not proportion to the increasing concentrations. Therefore, it is not appropriate
      to calculate the LC50 and LC95 of praziquantel. For evaluation of the interaction
      with the two drugs, praziquantel 0.1 or 0.2 MUg/mL, which may induce moderate or
      strong spasmodic contractions of the worm body and vesiculation along the worm
      surface, was combined with mefloquine 5, 6, or 7 MUg/mL. It was found that when
      mefloquine combined with praziquantel simultaneously or administered 1 h after
      addition of praziquantel, the spasmodic contraction of the male worm body was
      antagonized by mefloquine in various degrees according to the concentrations of
      mefloquine used. Meanwhile, praziquantel-induced weakened motor activity could be
      reversed by mefloquine. In female worms, morphological alterations and stimulated
      motor activity induced by mefloquine still developed. Interestingly, using these
      two regimens to combine mefloquine with praziquantel resulted in no impact or a
      decrease in worm mortality. On the other hand, praziquantel 0.2 MUg/mL
      administered within 17 h after mefloquine 5 or 6 MUg/mL promoted the damage to
      the tegument of the worms, which led to enhance the worm mortality compared with
      that of worms exposed to mefloquine alone. The results indicate that in vitro
      higher concentrations of praziquantel administered within 17 h after mefloquine
      may increase the effect against adult schistosomes, while praziquantel combined
      with mefloquine simultaneously or administered 1 h before addition of mefloquine
      exhibits no impact or decrease in the effect against schistosomes.

PMID- 21853221
TI  - [Pharmacological treatment for retinopathy of prematurity].
AB  - Mandatory screening performed by an experience ophthalmologist remains the most
      important pillar in the management of retinopathy of prematurity (ROP). The
      current gold standard for treatment of proliferative ROP is still panretinal
      laser photocoagulation, depending on severity, in combination with vitreoretinal
      surgery if necessary. The first case series of off-label intravitreal anti-VEGF
      treatment are encouraging. In addition to intravitreal anti-VEGF therapy, other
      treatment concepts such as supplementation with IGF-1 or omega-3 fatty acids also
      represent interesting pharmacological approaches to the management of ROP.
      However, larger controlled trials are required to validate the benefits and
      safety of these systemic treatment approaches.

PMID- 21853224
TI  - Morphological and molecular characterization and phylogenetic placement of
      Sarcocystis capreolicanis and Sarcocystis silva n. sp. from roe deer (Capreolus
      capreolus) in Norway.
AB  - Sarcocysts were isolated from the muscle tissue of three roe deer from
      southeastern Norway and examined by light microscopy, scanning electron
      microscopy and/or sequencing of the small subunit ribosomal RNA (ssu rRNA) gene.
      By light microscopy, four sarcocyst types were found, including those of
      Sarcocystis gracilis and Sarcocystis oviformis, which had been characterized
      previously. The third cyst type had about 10 MUm long, flexible, hair-like
      surface protrusions, consistent with those of Sarcocystis capreolicanis, and
      differed genetically from other known species. The name S. capreolicanis was
      therefore assigned to this sequence type. The fourth cyst type had densely
      packed, upright, finger-like surface protrusions, about 8 MUm long, and was
      morphologically similar to an unnamed Sarcocystis sp. reported from roe deer in
      other countries, and identical at the ssu rRNA gene to Sarcocystis sp. Type D
      previously reported from moose. This species was assigned the new name
      Sarcocystis silva. Both S. capreolicanis and S. silva displayed considerable
      intraspecific variation at the ssu rRNA gene. In phylogenetic analyses based on
      ssu rRNA gene sequences, S. capreolicanis grouped together with other canine
      transmitted Sarcocystis species, whereas S. silva was most closely related to
      Sarcocystis rangiferi and Sarcocystis tarandi of reindeer. Roe deer muscles
      containing numerous cysts of S. gracilis were fed to a silver fox (Vulpes vulpes)
      and a blue fox (Vulpes lagopus), both of which started shedding Sarcocystis
      sporocysts in their faeces 9 days later, and harboured numerous oocysts,
      measuring about 20 * 15 MUm, in their intestinal mucosa upon euthanasia 14 days
      post-inoculation. DNA derived from these oocysts was amplified and sequenced at
      the ssu rRNA gene and belonged to S. gracilis, confirming for the first time by
      molecular methods that foxes are definitive hosts for this species.

PMID- 21853225
TI  - A new species of the genus Heterobothrium (Monogenea: Diclidophoridae)
      parasitizing the gills of tiger puffer fish Tetraodon lineatus (Tetraodontidae).
      A light and scanning electron microscopic study.
AB  - In the present study, the morphology and morphometric characterization of
      Heterobothrium lineatus, a monogenean gill parasite infecting the gills and wall
      of the bronchial cavity of the tiger pufferfish Tetraodon lineatus, were
      described by means of light and scanning electron microscopy for the first time
      from the River Nile at Qena Governorate, South Valley, Egypt. In wet mount
      preparation, the adult worms exhibited an elongated body with anterior pointed
      and posterior broad ends. The adult worm measured 1.15-1.76 mm (1.53 +/- 0.2) in
      length and 0.30-0.42 mm (0.35 +/- 0.02) in width. Light and scanning electron
      microscopic observations showed the presence of two buccal organs situated
      anteriorly around the mouth opening. The opisthohaptor was subdivided into four
      pairs of clamps but had no isthmus separating it from the body proper. The
      present Heterobothrium species differs from all other described species in the
      genus, by its lower dimensions of the worm measurements and the presence of a
      copulatory organ armed with 12-15 genital hooks. Furthermore, it is easily
      distinguished from Heterobothrium tetrodonis and Heterobothrium okamotoi by the
      absence of a distinct isthmus, and resembles Heterobothrium lamothei described
      from the gills of Sphoeroides testodineus in Mexico in its general appearance and
      the presence of rectangular haptor with the fourth pair of clamps smaller than
      the previous ones.

PMID- 21853226
TI  - Anthelmintic effect of a methanol extract of Bombax malabaricum leaves on
      Paramphistomum explanatum.
AB  - Bombax malabaricum (family Bombacaceae) is used as anthelmintic in traditional
      system of medicine in Southern Punjab of Pakistan. The objective of this study
      was to evaluate the anthelmintic activity of the methanol extract of B.
      malabaricum leaves (MEBM). Live parasites (trematode: Paramphistomum explanatum)
      were collected from buffalo in 0.9% phosphate-buffered saline. It was incubated
      in Petri dishes at 37 +/- 1 degrees C in media containing either no extract
      (control) or MEBM, the test drug at 10, 25, 50, and 100 mg/ml dose level or
      albendazole, the standard drug at 10 mg/ml. The efficacy of the extract or
      albendazole was measured on the basis of the loss of spontaneous movement and/or
      death of the trematodes. Paralysis was considered when there is no movement
      unless shaken vigorously. Death was confirmed when the trematodes completely lost
      their motility, even when vigorously shaken or dipped in warm water (50 degrees
      C), followed by fading away of their body color. The trematodes, both drug
      treated and others, were further processed for SEM study using the standard
      method. All trematodes died with all the above-mentioned doses of MEBM within a
      short period of time (less than 45 min) which was statistically highly
      significant (p < 0.001). MEBM at 100 mg/ml showed maximum efficacy. It paralyzed
      and killed trematodes in 18.50 +/- 0.62 and 22.17 +/- 0.48 min, respectively. SEM
      study showed that MEBM-treated trematodes were stretched. The study established
      the anthelmintic activity of MEBM.

PMID- 21853227
TI  - Intraoperative cytopathological diagnosis of plasmocytoma of the optic nerve head
      using fine-needle aspiration.

PMID- 21853228
TI  - Intravitreous VEGF-A in eyes with massive vitreous hemorrhage.
AB  - PURPOSE/BACKGROUND: Although vascular endothelial growth factor (VEGF) is
      abundant in serum, the intraocular concentration of VEGF in eyes with massive
      vitreous hemorrhage (VH) is not well-known. The present study was conducted to
      elucidate the effects of a massive VH on intravitreous VEGF concentration.
      METHODS: Vitreous samples were obtained during vitrectomy: 12 samples from eyes
      with epiretinal membrane without diabetic retinopathy (DR), and nine samples from
      massive VH with no DR, such as age-related macular degeneration, rhegmatogenous
      VH, Terson's syndrome and macro-aneurysm rupture. Twelve samples were obtained
      from proliferative DR. VEGF was measured with an enzyme-linked immunosorbent
      assay (ELISA). Samples incubated with or without heparin were also examined for
      the release of VEGF binding to the vitreous body. The localization of VEGF and
      type II collagen in the vitreous was evaluated from immunohistochemistry.
      RESULTS: The concentration of VEGF was significantly higher in eyes with
      proliferative DR (821 +/- 949 pg/ml) than in non-DR with massive VH (2.75 +/- 7.5
      pg/ml, P < 0.01, chi-square test) or non-DR with no VH (less than detectable
      level, P < 0.01, chi-square test) There was no statistically significant
      difference between eyes with massive VH and non-diabetic eyes without VH.
      Treatment with heparin did not significantly affect the concentration of vitreous
      VEGF. VEGF was localized mainly in the clot from the results of an
      immunohistochemical analysis. CONCLUSIONS: Even with a massive VH, diffusible
      VEGF does not increase significantly in the liquid phase and is principally
      present in a clot. VH alone should not be an indication for vitrectomy from the
      point of view of VEGF-related pathology.

PMID- 21853229
TI  - Comparative study of vitrectomy versus intravitreous triamcinolone for diabetic
      macular edema on randomized paired-eyes.
AB  - BACKGROUND: The present study was performed to compare the effects of pars plana
      vitrectomy (PPV) and single intravitreaous triamcinolone acetonide (IVTA) on
      diabetic macular edema (DME) in paired eyes. METHODS: Prospective comparative
      study on randomized paired-eyes was carried out at two hospitals. Forty eyes of
      20 patients with bilateral DME were included. One randomly-selected eye was
      treated with PPV (PPV group), and the other eye was treated with IVTA (4 mg, IVTA
      group). The central macular thickness (CMT) measured by optical coherence
      tomography (OCT) and best-corrected visual acuity (BCVA) were monitored for 12
      months after treatment. Changes from baseline and differences between groups were
      analyzed using a mixed model. RESULTS: At 1 and 3 months, CMT decreased
      significantly in the IVTA group compared to baseline (p < 0.0001 both), but CMT
      then increased gradually and no significant difference was found at 12 months (p
      = 0.90). In the PPV group, CMT decreased continuously and reached a significant
      level at 12 months (p < 0.0001). CMT of the IVTA group was significantly less
      than that of the PPV group at 1 month (p = 0.009); however, there was no
      significant difference at 3 months. Conversely, CMT was significantly less in the
      PPV group than in the IVTA group at 12 months (p = 0.0003). The changes of BCVA
      paralleled those of CMT, but no significant difference was detected between
      baseline BCVA and any time point. CONCLUSIONS: Despite the short-term
      improvement, DME recurred 6 months after IVTA, while it remained resolved after
      PPV. Although this study did not reveal a significant change of BCVA with either
      treatment, PPV resolved DME more effectively than IVTA at 1 year.

PMID- 21853230
TI  - Fat repositioning via supraperiosteal dissection with internal fixation for tear
      trough deformity in an Asian population.
AB  - BACKGROUND: To investigate the efficacy and complications of fat repositioning
      via supraperiosteal dissection with internal fat-flap fixation for tear trough
      deformity in an Asian population. METHODS: This study is a retrospective chart
      review. From June 2005 to May 2010, 212 patients with lower eyelid fat prolapse
      and tear trough deformity underwent fat repositioning via supraperiosteal
      dissection with internal fat-flap fixation. Postoperative complications were
      recorded, and the degree of outcome satisfaction was obtained at the 6-month
      postoperative follow-up. RESULTS: In total, 142 patients underwent
      transconjunctival fat repositioning, and 70 received the transcutaneous approach
      for redundant lower lid skin and tear trough deformity. The level of satisfaction
      6 months after the operation was high: 152 patients rated their experience as
      very satisfied (71.7%), 54 as satisfied (25.5%) and six as acceptable (2.8%).
      None reported being dissatisfied or unhappy. No diplopia or evidence of granuloma
      formation in the lower eyelid or check area was noted. Four patients who suffered
      from significant ecchymosis and conjunctival chemosis with corneal exposure were
      managed with lubricants and resolved spontaneously. Three patients who underwent
      the transcutaneous approach and excess skin excision had the complication of
      lower lid ectropion; they received lateral tarsal strip procedures with good
      results. Three patients required revision to remove the residual lateral fat pad
      because of inadequate lateral orbital fat excision during the initial procedure.
      CONCLUSIONS: Fat repositioning via supraperiosteal dissection with internal fat
      flap fixation is a safe and effective method to create a youthful midface
      appearance for Asians with tear trough deformity.

PMID- 21853231
TI  - Femtosecond laser treatment of the crystalline lens: a 1-year study of possible
      cataractogenesis in minipigs.
AB  - BACKGROUND: To investigate the long-term stability and possible cataractogenesis
      after femtosecond laser treatment of the crystalline lens. METHODS: The
      crystalline lenses of ten Gottingen minipigs(r) underwent femtosecond laser
      treatment. During a subsequent 1-year follow-up, the pigs were monitored by means
      of slit-lamp examination of the anterior segment and Scheimpflug imaging of the
      lens. RESULTS: No laser-induced cataractogenesis was observed during the 1-year
      follow-up. The laser pattern showed a stable appearance under all examination
      devices. CONCLUSION: Femtosecond laser treatment seems to be no trigger for
      cataract formation. Moreover, the long-term stability of the laser pattern makes
      it suitable for applications such as presbyopia treatment.

PMID- 21853232
TI  - Assessing the impact of cue exposure on craving to gamble in university students.
AB  - We recruited a sample of university student gamblers (n = 48) to complete a web
      based battery of instruments in a study designed to assess the impact of imagery
      based versus photographic cue exposure on acute craving to gamble using the multi
      item Gambling Urge Scale (GUS; Raylu and Oei 2004). Although self-reported
      craving increased following both forms of cue exposure, the imagery script had a
      more pronounced impact than did examination of photographs of gambling-related
      stimuli. We also evaluated the association of the post-cue exposure GUS with
      other relevant measures, and found it correlated highly both with other
      questionnaires assessing craving to gamble and with other gambling-relevant
      characteristics (e.g., gambling-related problems, preoccupation with gambling,
      distorted gambling beliefs, gambling refusal self-efficacy, sensation seeking),
      but was not associated with social desirability bias. These findings support the
      use of the GUS-a brief multi-item scale that shows several key elements of
      construct, convergent, criterion and discriminant validity-to study the
      experience of craving in university student gamblers.

PMID- 21853234
TI  - Treatment for orbital diffuse large B-cell lymphoma in an elderly patient by
      autologous cytokine-induced killer cells.

PMID- 21853233
TI  - Association study on pathological gambling and polymorphisms of dopamine D1, D2,
      D3, and D4 receptor genes in a Korean population.
AB  - Several studies have reported that some dopaminergic receptor polymorphisms are
      associated with pathological gambling (PG). Considering that there are major race
      and ethnic group difference in dopaminergic polymorphisms, the result of genetic
      association studies should be confirmed in more homogeneous population to avoid
      problems of population stratification. The present study aimed to investigate
      whether selected polymorphisms in the dopamine receptors genes (DRD1, DRD2, DRD3,
      and DRD4) are associated with PG in Korean population which is consisted of only
      Korean ancestry. Subjects were 104 men with a diagnosis of PG and 114 unrelated
      age-matched normal control men. Genotyping was performed for the DRD1 gene -48
      A/G, DRD2 gene TaqI A, DRD3 gene Ser9Gly, and DRD4 gene exon III variable number
      tandem repeat polymorphisms. The method of multifactor dimensionality reduction
      (MDR) was used to analyze gene-gene interactions. There were no differences in
      the frequencies of any studied polymorphisms between patients with PG and normal
      controls. MDR analysis did not show a significant effect of the 4 dopamine
      receptor gene polymorphisms on susceptibility to PG (P > 0.05). The present study
      suggests that the analyzed polymorphisms of the dopamine receptor genes might not
      be associated with PG in a Korean population.

PMID- 21853235
TI  - Early recurrence of pseudomyxoma peritonei following treatment failure of
      cytoreductive surgery and perioperative intraperitoneal chemotherapy is
      indicative of a poor survival outcome.
AB  - BACKGROUND: The aim of this study was to identify predictors of early recurrence
      to optimize outcomes. METHODS: A comparison of clinicopathological factors
      between patients who developed early recurrence (<=12 months) and late recurrence
      (>12 months) was performed to identify predictors of treatment failure through
      univariate and multivariate analyses. Survival parameters were estimated using
      the Kaplan-Meier method. RESULTS: A total of 113 patients with a median PCI of 24
      (range, 2-39) underwent cytoreductive surgery. The median progression-free and
      overall survival was 48 and 104 months, respectively. Multivariate analysis
      identified prior operations >1, >=10 units of fresh frozen plasma (FFP)
      transfusion, incomplete cytoreduction and not undergoing definitive cytoreductive
      surgery within 12 months of diagnosis as predictors for disease recurrence.
      Twenty of 41 patients (49%) developed early recurrence. The median overall
      survival of patients who developed early recurrence was 38 months and in patients
      who did not develop early recurrence was 97 months (P = 0.002). Subgroup analysis
      of patients with recurrence identified the male gender (P = 0.028), elevated CA
      125 (P = 0.037), having elevated carcinoembryonic antigen (CEA), CA 125 and CA 19
      9 (P = 0.029), peritoneal cancer index >25 (P = 0.020), incomplete cytoreduction
      (P = 0.020), >6 units of blood transfusion (P = 0.020) and >10 units of FFP
      transfusion (P = 0.009) as factors associated with early recurrence. CONCLUSION:
      Early recurrence of pseudomyxoma peritonei occurs despite achieving high rates of
      oncologically optimal cytoreduction. The clinicopathologic factors associated
      with early recurrence identified in this study may inform us about patients at
      greatest risk of treatment failure during the post cytoreduction follow-up.

PMID- 21853236
TI  - Laparoscopic-assisted low and ultralow anterior resection for lower rectal cancer
      using the simple "Rectum Catcher" device and an intra-operative colonoscopy.
AB  - PURPOSE: We report the feasible technique in lower rectal surgery. MATERIALS AND
      METHODS: The Rectum Catcher (Matsumoto et al. in Surg Endosc 22:1905-1909, 2008)
      is made of stainless steel, with a circle of diameter 6 mm punched out at a
      distance of 5 mm from the top and covered with a short-cut T-tube. A vessel tape
      is inserted into the stainless steel and the short-cut T-tube. The rectum is
      grasped using the Rectum Catcher at a proximal rectum of the cancer, and the
      location of the cancer is confirmed using an intra-operative colonoscopy. In the
      next step, the Rectum Catcher is applied at the distal rectum of the cancer, and
      which easily occludes the rectum, and we confirm that the cancer is not at the
      distal rectum from the Rectum Catcher, using an intra-operative colonoscopy. The
      rectal lumen is irrigated. Then, the linear cutter is positioned just distal
      rectum to the Rectum Catcher, and the rectum is transected adequately. RESULTS:
      From January 2009 to the present, this study included 18 patients undergoing
      laparoscopic-assisted low and ultralow anterior resection for lower rectal
      cancer, using the Rectum Catcher and an intra-operative colonoscopy. Using the
      Rectum Catcher and an intra-operative colonoscopy, we can easily make a decision
      of the location of rectal cancer in lower rectum and irrigation of rectal lumen
      can be easily performed to safely cut the bowel being occluded, in the narrow
      laparoscopic view of the pelvic cavity. CONCLUSION: The combination between the
      Rectum Catcher and an intra-operative colonoscopy is useful for performing
      laparoscopic rectal surgery.

PMID- 21853237
TI  - Immune response and mechanical stress susceptibility in diseased oysters,
      Crassostrea virginica.
AB  - Eastern oysters, Crassostrea virginica, naturally infected with the parasite
      Perkinsus marinus were subjected to a mechanical stress by centrifugation, and
      immune parameters, pathological conditions, and gene expression of selected
      transcripts were compared to uninfected controls. Immune parameters were assessed
      by flow cytometry, pathology and parasites by histotechnology and fluid
      thioglycollate assays, and gene expression by quantitative RT-PCR. Irrespective
      of mechanical stress, an increased number of hemocytes were observed in P.
      marinus-infected oysters that corresponded to increased expression of genes that
      have been shown to be involved in inflammation and apoptosis, two processes
      associated with regulating immune cell populations. Mechanically stressed,
      diseased oysters showed histological gill abnormalities and aggregations of
      hemocytes in tissues not seen in stressed, uninfected oysters. Expression of a
      high-mobility group protein and hemocyte phagocytosis were significantly
      upregulated upon mechanical stress only in uninfected oysters. The results of
      this study demonstrate the role of inflammation in the oyster immune response
      including possible underlying molecular mechanisms. Furthermore, this study
      highlights the importance of considering mechanical stressors when characterizing
      oyster immune function.

PMID- 21853238
TI  - Naming and the role of the uncinate fasciculus in language function.
AB  - In this paper, an overview of the studies relating naming to the uncinate
      fasciculus is reported. With the introduction of contemporary neuroimaging
      techniques, namely of diffusion tensor imaging, white matter tracts have been
      investigated more thoroughly and possible changes in the uncinate fasciculus
      integrity have been correlated to different neuropsychological deficits. Although
      previous research has proposed a role of the left uncinate fasciculus on action
      and object naming or in semantic processing, a more recent study has suggested
      that naming famous people could be the most relevant task in which this bundle is
      involved, the semantic component being intact. The uncinate fasciculus connects
      the orbitofrontal cortex, involved in face encoding and in processing famous
      names, to the temporal pole, which is crucial in naming people. This conclusion
      is supported by the fact that tip-of-the-tongue states in older adults with
      reduced integrity of the uncinate fasciculus mainly concern proper names.

PMID- 21853239
TI  - Thunderclap headache triggered by micturition: responsive to nimodipine.
AB  - Primary thunderclap headache (TCH) is a rare condition, of which the onset can be
      triggered by coughing, exercise, and sexual activity. Micturition is a recognized
      trigger of secondary TCH with pheochromocytoma in bladder, but not of primary
      TCH. We describe a patient with an apparent primary TCH, which repeatedly
      occurred immediately after micturition until she achieved a therapeutic dosage of
      nimodipine.

PMID- 21853240
TI  - Operational temperature regulates anodic biofilm growth and the development of
      electrogenic activity.
AB  - The operational temperature of microbial fuel cell reactors influences biofilm
      development, and this has an impact on anodic biocatalytic activity. In this
      study, we compared three microbial fuel cell (MFC) reactors acclimated at 10
      degrees C, 20 degrees C and 35 degrees C to investigate the effect on biomass
      development, methanogenesis and electrogenic activity over time. The start-up
      time was inversely influenced by temperature, but the amount of biomass
      accumulation increased with increased temperatures, the 10 degrees C, 20 degrees
      C and 35 degrees C acclimated biofilms resulted in 0.57, 0.82 and 5.43 g biomass
      (volatile suspended solids) per litre respectively at 56 weeks of operation.
      Biofilm build-up on the 35 degrees C anode was further demonstrated by scanning
      electron microscopy, which showed large aggregations of biomass accumulating on
      the anode when compared to 10 degrees C and 20 degrees C biofilms. Biomass
      accumulation had a direct impact on biocatalytic performance, with the maximum
      power at 35 degrees C after 60 weeks of operation being 2.14 W m(-3) and power
      densities for the 10 degrees C and 20 degrees C reactors being and 4.29 W m(-3).
      Methanogenic activity was also shown to be higher at 35 degrees C, with a rate of
      10.1 mmol CH(4) biofilm per gram of volatile suspended solid (VSS) per day,
      compared to 0.28 mmol CH(4) per gram of VSS per day produced at 20 degrees C.
      These results demonstrate that higher MFC operating temperatures could be
      detrimental to the biocatalytic performance of electrochemically active bacteria
      in anodic biofilms due to biomass accumulation with enhanced development of non
      electrogenic communities (e.g. methanogens and fermenters), meaning that, over
      time, psychro- or mesophilic operation can have beneficial effects for the
      development of electrogenically active populations in the reactor.

PMID- 21853241
TI  - The incidence and clinical features of acute kidney injury secondary to ureteral
      calculi.
AB  - The aim of this study is to evaluate the incidence and clinical features of acute
      kidney injury (AKI) secondary to ureteral calculi. Between February 2002 and
      December 2009, the prevalence of AKI was 0.72% in our series of 2,073 cases of
      ureteral stones. The AKI patients received ureteroscopy or percutaneous
      nephrostomy as the primary treatment. The most popular symptom was significant
      decrease in urine output (75%, 12/16). Five cases (33.3%) were caused by
      bilateral ureteral stones, and 76.19% of the stones were located in the upper
      ureter, the mean size of single stone was 1.35 +/- 0.38 cm. The serum creatinine
      before treatment was 514.34 +/- 267.04 MUmol/L and the blood urea nitrogen before
      treatment was 21.31 +/- 10.24 mmol/L. 46.67% of the patients had a functional or
      anatomical solitary kidney unit. Our study suggests that risk factors for
      developing AKI in ureteral stone patients are bigger sized stones, ureteral
      stones in patients with only one functioning kidney or pre-existing kidney
      disease, and bilateral ureteral stones. Early effective drainage in these cases
      could decrease the risk developing AKI secondary to ureteral calculi.

PMID- 21853242
TI  - Prediction of calcium level in melamine-related urinary calculi with helical CT:
      diagnostic performance evaluation and clinical significance.
AB  - The aim of the study was to investigate the relationship between CT-attenuation
      and stone calcium level in melamine-related urinary calculi (MRUC). A total of 25
      MRUC with known composition and calcium level were included (11 uric acid stones,
      2 calcium oxalate stones and 12 mixture stones of uric acid and calcium oxalate).
      Of all, 18 renal stones accepted alkalization therapy except for 5 lower urinary
      tract stones and 2 stones of unknown position. With well-matched composition, 61
      adult urinary stones were included as controls. Every stone was scanned by
      helical CT (80 kV/120 kV, 300 mA, pitch 0.625 mm) and the highest CT-attenuation
      value measured. CT-attenuation values of MRUC increased gradually from uric acid
      stones, mixture stones to calcium oxalate stones, but were always lower than the
      values of controls. Furthermore, a strong positive correlation was found between
      stone CT-attenuation value and stone calcium level (n = 25, r (80kV) = 0.883, p =
      0.000; r (120kV) = 0.855, p = 0.000). Compared with alkalization-therapy-alone
      group, stone CT-attenuation values and stone calcium level in the comprehensive
      therapy group were significantly greater (CT(80kV) 1,057 +/- 639 vs. 172 +/- 61
      HU, p = 0.001; CT(120kV) 783 +/- 476 vs. 162 +/- 60 HU, p = 0.001; Ca 19.83 +/-
      7.48% vs. 1.30 +/- 1.51%, p = 0.000). Fisher's exact test suggested that the
      stones with higher CT-attenuation values tended to resist alkalization when 400
      HU served as the cutoff value (P (80kV) = 0.002, P (120kV) = 0.000). In
      conclusion, the study was the first to illustrate that the CT-attenuation value
      could reflect calcium level in MRUC and found that stones with higher CT
      attenuation value were not amenable to alkalization because they probably
      contained greater calcium. For those patients, we believe that comprehensive
      therapy will be the best choice.

PMID- 21853243
TI  - Clinical evaluation of indirect decompression treatments for degenerative adult
      idiopathic scoliosis.
AB  - STUDY DESIGN: Prospective case series. OBJECTIVE: Degenerative idiopathic
      scoliosis can be a cause of back pain. We sought to explore the feasibility and
      effectiveness of indirect decompression treatment in posterior correction and
      fusion for adult idiopathic scoliosis patients with radiculopathy and combined
      lateral olisthesis and/or foraminal stenosis. METHODS: Thirty seven degenerative
      adult idiopathic scoliosis patients with radiculopathy were recruited.
      Prostration or body traction alleviated the neurological deficit in these
      patients. Their symptoms were aggravated, when patients stood up. Imaging was
      used to assess lateral olisthesis and/or foraminal stenosis. All patients
      underwent posterior pedicle screw fixation, deformity correction, dorsal lamina
      and posterolateral bone grafting with the indirect decompression treatment.
      Clinical examinations including visual analog scale (VAS), oswestry disability
      index (ODI) scores, and images were performed pre- and post-operation and during
      follow-up visits. RESULTS: Twenty seven patients were followed for the average of
      30.8 months. No serious complication was observed. The cobb's angle, lateral
      olisthesis, thoracic kyphosis, thoracolumbar kyphosis, lumbar lordosis, VAS and
      ODI scores, coronal and sagittal balance were significantly improved among the
      patients who underwent the indirect decompression treatment. All patients had
      eliminated neurological deficit at their final follow-ups. CONCLUSIONS: The
      indirect decompression treatment in the posterior correction and fusion can be
      effective for adult idiopathic scoliosis patients with radiculopathy and combined
      lateral olisthesis and/or foraminal stenosis. This indicates the premise of
      strict operation indication.

PMID- 21853244
TI  - Ilizarov hip reconstruction in skeletally mature young patients with chronic
      unstable hip joints.
AB  - PURPOSE: Hip reconstruction with subtrochanteric valgus extension pelvic support
      osteotomy and distal femoral osteotomy for lengthening and varus correction is
      one of the options available for salvage of chronic unstable hips and is also
      known as Ilizarov hip reconstruction (IHR). This study evaluated the outcomes and
      complications associated with IHR in skeletally mature young patients. METHODS:
      Twelve patients (7 males, 5 females) with a mean age of 23 years underwent IHR
      for chronically dislocated hips due to various causes. Preoperative clinical and
      radiological evaluations were used to determine the site of osteotomies and the
      required angulations. Postoperatively the patients were followed up clinically
      and radiologically for a minimum of 36 months. Ilizarov fixator was removed when
      adequate lengthening was achieved and there was radiological evidence of union.
      Harris Hip Score was used to document hip function preoperatively and at final
      evaluation. RESULTS: Significant improvements occurred in limb length discrepancy
      (LLD) 5.11 cm preoperatively to 0.9 cm at final evaluation, Harris Hip Score
      44.33 points preoperatively to 70.83 points (p < 0.0001) at final evaluation.
      Trendelenberg sign disappeared completely in nine patients and was delayed in
      three at final evaluation. The abduction at the hip increased from the
      preoperative mean of 12.08 degrees  (range 0 degrees -25 degrees ) to 22.5
      degrees  (range 15 degrees -35 degrees ) postoperatively. The fixed flexion
      deformity at the hip decreased from 22 degrees  (range 10 degrees -35 degrees )
      preoperatively to 3 degrees  postoperatively (range 0 degrees -10 degrees ). The
      amount of free flexion at the operated hips decreased from the preoperative mean
      of 88.33 degrees  (range 70 degrees -120 degrees ) to 70.42 degrees  (range 45
      degrees -105 degrees ) at final follow up. The mean fixator interval was 7.33
      months (5-12 months) and the mean follow up duration was 59.4 months (38-86
      months). CONCLUSIONS: IHR is effective in improving the hip biomechanics,
      correcting the LLD and eliminating the Trendelenberg sign. Lengthy period of
      fixator wear, knee stiffness and pin tract infections, though minor are known
      limitations of this procedure.

PMID- 21853245
TI  - The determinants of serum vitamin D levels in participants in a melanoma case
      control study living in a temperate climate.
AB  - BACKGROUND: We report the determinants of serum levels of vitamin D in a U.K.
      melanoma case-control study benefitting from detailed exposure and genotyping
      data. METHODS: Sun exposure, supplemental vitamin D, and SNPs reported to be
      associated with serum levels were assessed as predictors of a single serum 25
      hydroxyvitamin D3 measurement adjusted for season, age, sex, and body mass index.
      RESULTS: Adjusted analyses showed that vitamin D levels were sub-optimal
      especially in the sun-sensitive individuals (-2.61 nmol/L, p = 0.03) and for
      inheritance of a genetic variant in the GC gene coding for the vitamin D-binding
      protein (-5.79 for heterozygotes versus wild type, p = <0.0001). Higher levels
      were associated with sun exposure at the weekend in summer (+4.71 nmol/L per
      tertile, p = <0.0001), and on hot holidays (+4.17 nmol/L per tertile, p =
      <0.0001). In smoothed scatter plots, vitamin D levels of 60 nmol/L in the non-sun
      sensitive individuals were achieved after an average 6 h/day summer weekend sun
      exposure but not in the sun-sensitive individuals. Users of supplements had
      levels on average 11.0 nmol/L higher, p = <0.0001, and achieved optimal levels
      irrespective of sun exposure. CONCLUSIONS: Sun exposure was associated with
      increased vitamin D levels, but levels more than 60 nmol/L were reached on
      average only in individuals reporting lengthy exposure (>=12 h/weekend). The sun
      sensitive individuals did not achieve optimal levels without supplementation,
      which therefore should be considered for the majority of populations living in a
      temperate climate and melanoma patients in particular. Inherited variation in
      genes such as GC is a strong factor, and carriers of variant alleles may
      therefore require higher levels of supplementation.

PMID- 21853246
TI  - Correlation between external and internal respiratory motion: a validation study.
AB  - PURPOSE: In motion-compensated image-guided radiotherapy, accurate tracking of
      the target region is required. This tracking process includes building a
      correlation model between external surrogate motion and the motion of the target
      region. A novel correlation method is presented and compared with the commonly
      used polynomial model. METHODS AND MATERIALS: The CyberKnife system (Accuray,
      Inc., Sunnyvale/CA) uses a polynomial correlation model to relate externally
      measured surrogate data (optical fibres on the patient's chest emitting red
      light) to infrequently acquired internal measurements (X-ray data). A new
      correlation algorithm based on E -Support Vector Regression (SVR) was developed.
      Validation and comparison testing were done with human volunteers using live 3D
      ultrasound and externally measured infrared light-emitting diodes (IR LEDs).
      Seven data sets (5:03-6:27 min long) were recorded from six volunteers. RESULTS:
      Polynomial correlation algorithms were compared to the SVR-based algorithm
      demonstrating an average increase in root mean square (RMS) accuracy of 21.3%
      (0.4 mm). For three signals, the increase was more than 29% and for one signal as
      much as 45.6% (corresponding to more than 1.5 mm RMS). Further analysis showed
      the improvement to be statistically significant. CONCLUSION: The new SVR-based
      correlation method outperforms traditional polynomial correlation methods for
      motion tracking. This method is suitable for clinical implementation and may
      improve the overall accuracy of targeted radiotherapy.

PMID- 21853247
TI  - Markers of uremia and pericardial effusion in peritoneal dialysis.
AB  - BACKGROUND: Inadequate dialysis causes accumulation of toxic residues that may
      lead to the development of dialysis-associated pericardial effusion, but several
      other factors could be associated with this abnormality. The purpose of this
      study was to evaluate clinical risk factors to asymptomatic pericardial effusion
      in peritoneal dialysis. METHODS: This cross-sectional study included 34 patients
      aged >= 18 years on peritoneal dialysis for at least 3 months, who showed no
      symptomatic pericardial effusion, hepatic cirrhosis, neoplasias, lupus or
      amputations, none in minoxidil use. Asymptomatic pericardial effusion was
      diagnosed by echocardiography. Risk factors were evaluated by logistic regression
      and Roc curve. Significance level was set at P < 0.05. RESULTS: Patient age was
      51 +/- 15.9 years. Of the 34 patients enrolled, 16 were men and 11 diabetic. Five
      of them presented pericardial effusion. Logistic regression identifies low
      hemoglobin level (RR 0.454 CI 95%: 0.225-0.913; P = 0.027), low phase angle (RR
      0.236 CI 95%: 0.057-0.984; P = 0.048) and low Kt/V (RR 0.001 CI 95%: 0.0-0.492; P
      = 0.03) as risk factors to pericardial effusion. Roc curve showed that hemoglobin
      levels below 12.2 g/dL, Kt/V lower than 1.9 and phase angle lower than 4.5
      degrees  were the best cutoffs to predict pericardial effusion. Four patients
      showed these three parameters in the unfavorable range, and all these four
      patients presented pericardial effusion. The other patient with pericardial
      effusion had two of these parameters reduced. CONCLUSIONS: These findings
      corroborate the hypothesis that uremia plays a significant role in the
      pathogenesis of dialysis-associated pericardial effusion.

PMID- 21853248
TI  - Genome-enabled determination of amino acid biosynthesis in Xanthomonas campestris
      pv. campestris and identification of biosynthetic pathways for alanine, glycine,
      and isoleucine by 13C-isotopologue profiling.
AB  - To elucidate the biosynthetic pathways for all proteinogenic amino acids in
      Xanthomonas campestris pv. campestris, this study combines results obtained by in
      silico genome analysis and by (13)C-NMR-based isotopologue profiling to provide a
      panoramic view on a substantial section of bacterial metabolism. Initially,
      biosynthesis pathways were reconstructed from an improved annotation of the
      complete genome of X. campestris pv. campestris B100. This metabolic
      reconstruction resulted in the unequivocal identification of biosynthesis routes
      for 17 amino acids in total: arginine, asparagine, aspartate, cysteine,
      glutamate, glutamine, histidine, leucine, lysine, methionine, phenylalanine,
      proline, serine, threonine, tryptophan, tyrosine, and valine. Ambiguous pathways
      were reconstructed from the genome data for alanine, glycine, and isoleucine
      biosynthesis. (13)C-NMR analyses supported the identification of the
      metabolically active pathways. The biosynthetic routes for these amino acids were
      derived from the precursor molecules pyruvate, serine, and pyruvate,
      respectively. By combining genome analysis and isotopologue profiling, a
      comprehensive set of biosynthetic pathways covering all proteinogenic amino acids
      was unraveled for this plant pathogenic bacterium, which plays an important role
      in biotechnology as a producer of the exopolysaccharide xanthan. The data
      obtained lay ground for subsequent functional analyses in post-genomics and
      biotechnology, while the innovative combination of in silico and wet lab
      technology described here is promising as a general approach to elucidate
      metabolic pathways.

PMID- 21853249
TI  - Implants in the severely resorbed mandibles: whether or not to augment? What is
      the clinician's preference?
AB  - INTRODUCTION: The aim of this study is to inventory in the Netherlands which
      therapy is the clinician's first choice when restoring the edentulous mandible.
      MATERIAL AND METHODS: A questionnaire was sent to all Dutch Oral and
      Maxillofacial surgeons. As part of this, the surgeons were invited to treat five
      virtual edentulous patients, differing only in mandibular residual height.
      RESULTS: In cases of a sufficient residual height of 15 mm, all surgeons were in
      favour to insert solely two implants to anchor an overdenture. In case of a
      residual height of 12 mm, 10% of the surgeons choose for an augmentation
      procedure. If a patient was presented with a mandibular height of 10 mm, already
      40% of the OMF surgeons executed an augmentation procedure. Most (80%) surgeons
      prefer the (anterior) iliac crest as donor site. The choice of 'whether or not to
      augment' was not influenced by the surgeon's age; however, the hospital, where he
      was trained, did. Surgeons trained in Groningen were more in favour of installing
      short implants in mandibles with reduced vertical height. DISCUSSION: As the
      option overdenture supported on two interforaminal implants is reimbursed by the
      Dutch health assurance, this treatment modality is very popular in the
      Netherlands. From a point of costs and to minimize bypass comorbidity, surgeons
      should be more reluctant in executing augmentation procedures to restore the
      resorbed edentulous mandible as it is dated in literature that also in mandibles
      with a residual height of 10 mm or less, solely placing implants, thus without an
      augmentation procedure in advance, is a reliable treatment option.

PMID- 21853250
TI  - Elevated progesterone in GnRH agonist down regulated in vitro fertilisation
      (IVFICSI) cycles reduces live birth rates but not embryo quality.
AB  - OBJECTIVE: To assess the impact of pre-hCG elevated progesterone on live birth
      outcomes during GnRH agonist long down regulated protocol assisted reproduction
      cycles. DESIGN: Retrospective cohort study. SETTING: Single Centre Private IVF
      Clinic. PATIENTS: A total of 582 consecutive cycles of IVF/ICSI in 2003.
      INTERVENTIONS: All patients underwent a long down-regulation protocol, controlled
      ovarian stimulation and IVF/ICSI. Serum progesterone concentrations were measured
      just prior to HCG administration. 253 patients were followed to 2009 for outcomes
      of their frozen embryo cycles. MAIN OUTCOME MEASURE: Live birth rate in fresh and
      frozen cycles. RESULTS: Patients in the upper quartile pre-hCG progesterone
      concentration (>= 5.4 pmol/L) had a higher final estradiol level, more oocytes
      collected and more usable embryos, when compared to those with lower quartiles.
      They also had lower live birth rates per cycle started (21.9% vs. 15%, P < 0.05).
      However, live birth rates from frozen embryo cycles were not significantly
      different between the groups. CONCLUSIONS: Pre-hCG progesterone elevation leads
      to lower live birth rates in stimulated IVF cycles. Live birth rates achieved
      with frozen embryos in the high progesterone cycles suggest, that pre-hCG
      progesterone elevation negatively affects endometrial receptivity without
      adversely affecting embryo quality.

PMID- 21853251
TI  - Association between menopausal symptoms and metabolic syndrome in postmenopausal
      women.
AB  - PURPOSE: Menopausal symptoms are major concerns of postmenopausal women.
      Metabolic syndrome (MetS) is a risk factor for cardiovascular disease, and
      menopause is associated with an increased prevalence of MetS. The purpose of this
      study was to determine the association between menopausal symptoms and MetS in
      postmenopausal women. METHODS: We selected 183 women who attended St. Vincent
      Hospital of the Catholic University of Korea in 2008 and 2009 and divided them
      into two groups (with and without MetS). Menopausal status was assessed with the
      Menopause Rating Scale (MRS) questionnaire. The body mass index and waist-to-hip
      ratio were determined, and the serum fasting glucose, lipid profile, and blood
      pressure were measured in all participants. RESULTS: Of 183 postmenopausal women,
      64 (35.0%) had MetS. A significant increase was observed in the total MRS score
      and the total somatic symptom subscale score in the MetS group (p = 0.021, p =
      0.043, respectively). Vasomotor symptoms such as hot flashes and sweating
      occurred with higher frequency in the MetS group than in those without MetS (p =
      0.034). High triglyceride levels and an increase of the number of components of
      MetS were associated with a higher total subscale score of somatic symptoms (p =
      0.044, p = 0.039, respectively). CONCLUSIONS: These results showed that a higher
      total subscale score and a higher frequency of somatic symptoms such as hot
      flashes and sweating were present in the MetS group. Larger scale studies are
      needed to clarify the association between other menopausal symptoms and MetS in
      postmenopausal women.

PMID- 21853253
TI  - Chloroplastic NADPH oxidase-like activity-mediated perpetual hydrogen peroxide
      generation in the chloroplast induces apoptotic-like death of Brassica napus leaf
      protoplasts.
AB  - Despite extensive research over the past years, regeneration from protoplasts has
      been observed in only a limited number of plant species. Protoplasts undergo
      complex metabolic modification during their isolation. The isolation of
      protoplasts induces reactive oxygen species (ROS) generation in Brassica napus
      leaf protoplasts. The present study was conducted to provide new insight into the
      mechanism of ROS generation in B. napus leaf protoplasts. In vivo localization of
      H(2)O(2) and enzymes involved in H(2)O(2) generation and detoxification,
      molecular antioxidant-ascorbate and its redox state and lipid peroxidation were
      investigated in the leaf and isolated protoplasts. Incubating leaf strips in the
      macerating enzyme (ME) for different duration (3, 6, and 12 h) induced
      accumulation of H(2)O(2) and malondialdehyde (lipid peroxidation, an index of
      membrane damage) in protoplasts. The level of H(2)O(2) was highest just after
      protoplast isolation and subsequently decreased during culture. Superoxide
      generating NADPH oxidase (NOX)-like activity was enhanced, whereas superoxide
      dismutase (SOD) and ascorbate peroxidase (APX) decreased in the protoplasts
      compared to leaves. Diaminobenzidine peroxidase (DAB-POD) activity was also lower
      in the protoplasts compared to leaves. Total ascorbate content, ascorbate to
      dehydroascorbate ratio (redox state), were enhanced in the protoplasts compared
      to leaves. Higher activity of NOX-like enzyme and weakening in the activity of
      antioxidant enzymes (SOD, APX, and DAB-POD) in protoplasts resulted in excessive
      accumulation of H(2)O(2) in chloroplasts of protoplasts. Chloroplastic NADPH
      oxidase-like activity mediated perpetual H(2)O(2) generation probably induced
      apoptotic-like cell death of B. napus leaf protoplasts as indicated by parallel
      DNA laddering and decreased mitochondrial membrane potential.

PMID- 21853254
TI  - XYLEM INTERMIXED WITH PHLOEM1, a leucine-rich repeat receptor-like kinase
      required for stem growth and vascular development in Arabidopsis thaliana.
AB  - The regulation of cell specification in plants is particularly important in
      vascular development. The vascular system is comprised two differentiated tissue
      types, the xylem and phloem, which form conductive elements for the transport of
      water, nutrients and signaling molecules. A meristematic layer, the procambium,
      is located between these two differentiated cell types and divides to initiate
      vascular growth. We report the identification of a receptor-like kinase (RLK)
      that is expressed in the vasculature. Histochemical analyses of mutants in this
      kinase display an aberrant accumulation of highly lignified cells, typical of
      xylem or fiber cells, within the phloem. In addition, phloem cells are sometimes
      located adjacent to xylem cells in these mutants. We, therefore, named this RLK
      XYLEM INTERMIXED WITH PHLOEM 1 (XIP1). Analyses of longitudinal profiles of xip1
      mutant stems show malformed cell files, indicating defects in oriented cell
      divisions or cell morphology. We propose that XIP1 prevents ectopic lignification
      in phloem cells and is necessary to maintain the organization of cell files or
      cell morphology in conductive elements.

PMID- 21853252
TI  - The effect of carnitine on Arabidopsis development and recovery in salt stress
      conditions.
AB  - Carnitine exists in all living organisms where it plays diverse roles. In animals
      and yeast, it is implicated in lipid metabolism and is also associated with
      oxidative stress tolerance. In bacteria, it is a major player in osmotic stress
      tolerance. We investigate the carnitine function in plants and our present work
      shows that carnitine enhances the development and recovery of Arabidopsis
      thaliana seedlings subjected to salt stress. Biological data show that exogenous
      carnitine supplies improve the germination and survival rates of seedlings grown
      on salt-enriched medium, in a manner comparable to proline. Both compounds are
      shown to improve seedling survival under oxidative constraint meaning that they
      may act on salt stress through antioxidant properties. A transcriptome analysis
      of seedlings treated with exogenous carnitine reveals that it modulates the
      expression of genes involved in water stress and abscisic acid responses.
      Analyses of the abscisic acid mutants, aba1-1 and abi1-1, indicate that carnitine
      and proline may act through a modulation of the ABA pathway.

PMID- 21853255
TI  - Design and synthesis of a terbium(III) complex-based luminescence probe for time
      gated luminescence detection of mercury(II) ions.
AB  - Time-gated luminescence detection technique using lanthanide complexes as
      luminescent probes is a useful and highly sensitive method. However, the
      effective application of this technique is limited by the lack of the target
      responsive luminescent lanthanide complexes that can specifically recognize
      various analytes in aqueous solutions. In this work, a dual-functional ligand
      that can form a stable complex with Tb(3+) and specifically recognize Hg(2+) ions
      in aqueous solutions, N,N,N(1),N(1)-{[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-4-[N,N
      bis(3",6"-dithiaoctyl)-aminomethyl]- pyridine]} tetrakis(acetic acid) (BBAPTA),
      has been designed and synthesized. The luminescence of its Tb(3+) complex is
      weak, but can be effectively enhanced upon reaction with Hg(2+) ions in aqueous
      solutions. The luminescence response investigations of BBAPTA-Tb(3+) to various
      metal ions indicate that the complex has a good luminescence sensing selectivity
      for Hg(2+) ions, but not for other metal ions. Thus a highly sensitive time-gated
      luminescence detection method for Hg(2+) ions was developed by using BBAPTA
      Tb(3+) as a luminescent probe. The dose-dependent luminescence enhancement of the
      probe shows a good linearity with a detection limit of 17 nM for Hg(2+) ions.
      These results demonstrated the efficacy and advantages of the new Tb(3+) complex
      based luminescence probe for the sensitive and selective detection of Hg(2+)
      ions.

PMID- 21853256
TI  - Spectrofluorimetric determination of etodolac, moxepril HCl and fexofenadine HCl
      using europium sensitized fluorescence in bulk and pharmaceutical preparations.
AB  - A simple, selective and sensitive luminescence method has been developed for the
      assay of etodolac (I), moxepril HCl (II) and fexofenadine HCl (III) in bulk drug
      and pharmaceutical formulations. The method is based on the luminescence
      sensitization of europium (Eu(3+)) by complexation with the studied drugs. The
      fluorescence intensities of the products were measured at 667 nm for (I) and at
      615 for (II) and (III) while exciting at 276 for all the studied drugs. The
      fluorescence intensity was directly proportional to the concentration over the
      range (20-280), (40-240) and (30-80) ng/ml with limits of detection (LOD) = 0.93,
      0.92 and 0.95 MUg/ml for drugs I, II and III respectively. Optimum conditions for
      the formation of the complex in methanol were carefully studied. The proposed
      method was successfully applied for the assay of the studied drugs in
      pharmaceutical formulations with excellent recovery.

PMID- 21853257
TI  - Microwave-assisted aqueous synthesis of highly luminescent carboxymethyl chitosan
      coated CdTe/CdS quantum dots as fluorescent probe for live cell imaging.
AB  - This paper describes the development of a simplified and rapid method for the
      aqueous synthesis of quantum dots (QDs) with CdTe cores and gradient CdS external
      shells (CdTe/CdS QDs) aided by microwave irradiation. Several synthesis
      parameters, such as molar ratio of reagents, pH, reaction temperature, and
      reaction time, were studied in details. Under the optimized conditions, highly
      effective CdTe/CdS QDs could be synthesized in aqueous phase in only 15 min. In
      order to improve the biocompatibility of the CdTe/CdS QDs, these QDs were then
      interacted with carboxymethyl chitosan (CMC) so as they could be used as
      fluorescent probes in the aqueous phase. With the incorporation of CMC, the
      stability of modified QDs was found to have improved significantly (from 4 months
      to more than 10 months at room temperature). The photoluminescence quantum yield
      (PLQY) of the modified QDs could reach 75%, other parameters include a full width
      at half maximum of the emission (FWHM) spectrum as 40 ~ 60 nm, and an average
      size, estimated from electron microscopic images, as 3.5 nm. As fluorescent
      probes, these modified QDs were successfully used for imaging live Madin-Darby
      canine kidney (MDCK) cells, in which the preliminary results indicated that these
      modified QDs demonstrated good biocompatibility and showed promising applications
      for bio-labeling and imaging.

PMID- 21853258
TI  - DFT/TDDFT study on the electronic structure and spectral properties of diphenyl
      azafluoranthene derivative.
AB  - Paper reports the DFT/TDDFT study on the electronic structure and spectral
      properties of the five-membered annulated diphenyl azafluoranthene derivative 1,3
      diphenyl-3H-indeno[1,2,3-de]pyrazolo[3,4-b]quinoline (DPIPQ) by means of
      polarizable continuum model (PCM) and Onsager reaction field approaches at the
      B3LYP/6-31+G(d,p) level of theory. The results of calculations are compared with
      the optical absorption and fluorescence spectra as well as with the cyclic
      voltammetry data. The DFT/TDDFT/PCM approaches exhibit rather good quantitative
      agreement regarding the spectral position of the first absorption band; the
      discrepancy between the experiment and theory is less than 0.06 eV (linear
      response approach) or 0.25 eV (state specific approach). As for the fluorescence
      emission the TDDFT/PCM calculations underestimate the transition energy on about
      of 0.7-0.8 eV. Such discrepancy should be attributed to insufficient quality of
      the TDDFT/PCM optimization in the excited state. Ignoring the geometrical
      relaxation in the excited state provides considerably better agreement between
      the experiment and theory; discrepancy is less than 0.1-0.22 eV depending on a
      solvent polarity. The dominant influence on the fluorescence emission results
      mainly from the solvent reorganization in the excited state whereas the solute
      relaxation is indeed weak and may be ignored.

PMID- 21853259
TI  - Development of novel rat model for high-fat and high-cholesterol diet-induced
      steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr.
AB  - OBJECTIVES: Patients with nonalcoholic fatty liver disease are increasing
      worldwide, and preventive measures are an urgent need and primary concern today.
      AIM: This study aimed to develop and clarify the usefulness of the SHRSP5/Dmcr
      rat, derived from a stroke-prone spontaneously hypertensive rat, as a novel
      animal model for time-course analysis of steatohepatitis and the severe fibrosis
      progression often observed in the disease. METHODS: Ten-week-old male SHRSP5/Dmcr
      rats were divided into six groups: half were fed a high-fat and high-cholesterol
      containing diet (HFC diet), and the others the control, stroke-prone (SP) diet
      for 2, 8, and 14 weeks. RESULTS: The HFC diet significantly increased serum
      transaminase and gamma glutamyl transpeptidase activities, tumor necrosis factor
      alpha levels, and serum and hepatic total cholesterol levels over time. In
      contrast, this diet decreased serum albumin, glucose, and adiponectin levels
      throughout or the later stage of the feeding period, but did not influence serum
      insulin levels. Histopathologically, the HFC diet increased microvesicular
      steatosis, and focal or spotty necrosis with lymphocyte infiltrations were
      observed in the liver at 2 weeks, macrovesicular steatosis, ballooned hepatocytes
      with Mallory-Denk body formation in some, and multilobular necrosis and fibrosis
      at 8 weeks. Interestingly, this fibrosis formed a honeycomb network at 14 weeks.
      These changes are very similar to those observed in patients with non-alcoholic
      steatohepatitis. CONCLUSIONS: SHRSP5/Dmcr rats appear to be a useful model for
      analyzing the time-dependent changes of HFC diet-induced steatohepatitis and
      fibrosis progression.

PMID- 21853260
TI  - Introduction of an examination and treatment for Helicobacter pylori infection in
      high school health screening.
AB  - BACKGROUND: Recently, a significant relationship between gastric cancer and
      Helicobacter pylori infection has been proven. The purpose of this study was to
      elucidate the actual conditions of H. pylori infection in Japanese teenagers.
      METHODS: The study subjects were students at a certain high school between 2007
      and 2009. They were first examined with a urinary rapid test kit based on
      immunochromatographic technology [corrected] for detection of the antibody to H.
      pylori (RAPIRAN(r)). [corrected]. Students who tested positive on this screening
      examination visited Shinshu University Hospital and received
      esophagogastroduodenoscopy, and biopsy samples were taken to examine their H.
      pylori status. The resolution of H. pylori infection was assessed by urea breath
      test. RESULTS: For 3 years, 1,224 of 1,232 students (99.4%) received a screening
      examination for H. pylori infection. Sixty-four of these 1,224 students (5.2%)
      were found to be positive for H. pylori. Thirty of these 64 H. pylori-positive
      students visited our hospital, and 24 of them (80%) were confirmed to be infected
      by H. pylori. The most common endoscopic findings for students with H. pylori
      infection were nodular gastritis (58.3%) and closed-type atrophic gastritis
      (45.8%). Histological findings showed no evidence of intestinal metaplasia,
      except in one of the students. All 24 students were successfully cured of H.
      pylori infection. If this procedure were to be introduced into the nationwide
      health screening at Japanese high schools, we calculated that the cost of the
      prevention of a gastric cancer would be 454,073 yen for each person. CONCLUSIONS:
      The low rate of prevalence of H. pylori infection in Japanese teenagers would
      make it possible to perform examinations and carry out treatment for this
      infection in high school health screenings from the standpoint of medical
      economy.

PMID- 21853261
TI  - Activities of DNA base excision repair enzymes in liver and brain correlate with
      body mass, but not lifespan.
AB  - Accumulation of DNA lesions compromises replication and transcription and is thus
      toxic to cells. DNA repair deficiencies are generally associated with cellular
      replicative senescence and premature aging syndromes, suggesting that efficient
      DNA repair is required for normal longevity. It follows that the evolution of
      increasing lifespan amongst animal species should be associated with enhanced DNA
      repair capacities. Although UV damage repair has been shown to correlate
      positively with mammalian species lifespan, we lack similar insight into many
      other DNA repair pathways, including base excision repair (BER). DNA is
      continuously exposed to reactive oxygen species produced during aerobic
      metabolism, resulting in the occurrence of oxidative damage within DNA. Short
      patch BER plays an important role in repairing the resultant oxidative lesions.
      We therefore tested whether an enhancement of BER enzyme activities has occurred
      concomitantly with the evolution of increased maximum lifespan (MLSP). We
      collected brain and liver tissue from 15 vertebrate endotherm species ranging in
      MLSP over an order of magnitude. We measured apurinic/apyrimidinic (AP)
      endonuclease activity, as well as the rates of nucleotide incorporation into an
      oligonucleotide containing a single nucleotide gap (catalyzed by BER polymerase
      beta) and subsequent ligation of the oligonucleotide. None of these activities
      correlated positively with species MLSP. Rather, nucleotide incorporation and
      oligonucleotide ligation activities appeared to be primarily (and negatively)
      correlated with species body mass.

PMID- 21853263
TI  - Longitudinal study of variation in body mass index in middle-aged UK females.
AB  - The importance of changing patterns of obesity in society and its implications
      for public health are well recognized. However, the adult life course of body
      mass index (BMI) changes in individuals over time is largely unknown and has
      mostly been extrapolated from cross-sectional studies. The present study examines
      individual specific variation of BMI during a 15-year follow-up period in a
      community-based sample of UK females. We attempted to establish whether there is
      a common, generalized pattern which captures variation in BMI over time. The
      participants of this study belong to a prospective population cohort of British
      women studied intensively since 1989: the Chingford Study. The sample originally
      consisted of 1,003 women aged 45-68 years, who were assessed annually for BMI
      during follow-up period. Polynomial regression models were used to assess
      longitudinal BMI variation. We observed a great stability in individual BMI
      variation during the follow-up period, reflected by high correlations between the
      baseline BMI and follow-up BMI 10 and 15 years later (r = 0.876, N = 810, and r =
      0.824, N = 638, respectively). We also found that three different major age
      related patterns in BMI could be clearly identified: no change in 30.6% in 58% it
      increased and in 11.4% it decreased with age. Thus, our data suggest that
      individual age-related changes in BMI are very different. Therefore, simply
      combining all individuals into groups by any other criteria (age, sex, etc.) and
      overlooking the distinctive patterns of BMI change may lead to biased inferences
      in epidemiologic and etiologic research of the future.

PMID- 21853262
TI  - The association between systemic inflammation and cognitive performance in the
      elderly: the Sydney Memory and Ageing Study.
AB  - Inflammation may contribute to cognitive decline and dementia. This study
      examined the cross-sectional relationships between markers of systemic
      inflammation (C-reactive protein, interleukins-1beta, -6, -8, -10, -12,
      plasminogen activator inhibitor, serum amyloid A, tumour necrosis factor-alpha
      and vascular adhesion molecule-1) and cognitive function in 873 non-demented
      community-dwelling elderly participants aged 70-90 years. Regression analyses
      were performed to determine the relationships between cognitive domains and
      inflammatory markers, controlling for age, sex, education, cardiovascular risk
      factors, obesity and other metabolic factors, smoking, alcohol consumption,
      depression and presence of the apolipoprotein epsilon4 genotype. Regression
      analyses were repeated using four factors derived from a factor analysis of the
      cognitive tests. After Bonferroni correction for multiple testing, associations
      remained between raised levels of interleukin-12 and reduced performance in
      processing speed. Marked sex differences were noted in the abovementioned
      findings, with only females being significantly affected. Using the four factors
      derived from the factor analyses of cognitive test as dependent variables,
      interleukins-12 and -6 were both associated with the processing speed/executive
      function factor, even after controlling for relevant confounding factors. Thus,
      markers of systemic inflammation are related to cognitive deficits in a non
      clinical community-dwelling elderly population, independent of depression,
      cardiovascular or metabolic risk factors, or presence of apolipoprotein epsilon4
      genotype. Additional research is required to elucidate the pathophysiology and
      longitudinal development of these relationships.

PMID- 21853264
TI  - Low handgrip strength is a predictor of osteoporotic fractures: cross-sectional
      and prospective evidence from the Hong Kong Osteoporosis Study.
AB  - Handgrip strength (HGS) is a potentially useful objective parameter to predict
      fracture since it is an indicator of general muscle strength and is associated
      with fragility and propensity to fall. Our objective was to examine the
      association of HGS with fracture, to evaluate the accuracy of HGS in predicting
      incident fracture, and to identify subjects at risk of fracture. We analyzed a
      cross-sectional cohort with 2,793 subjects (1,217 men and 1,576 women aged 50-101
      years) and a subset of 1,702 subjects which were followed for a total of 4,855
      person-years. The primary outcome measures were prevalent fractures and incident
      major fragility fractures. Each standard deviation (SD) reduction in HGS was
      associated with a 1.24-fold increased odds for major clinical fractures even
      after adjustment for other clinical factors. A similar result was obtained in the
      prospective cohort with each SD reduction in HGS being associated with a 1.57
      fold increased hazard ratio of fracture even after adjustment for clinical
      factors. A combination of HGS and femoral neck bone mineral density (FN BMD) T
      score values (combined T-score), together with other clinical factors, had a
      better predictive power of incident fractures than FN BMD or HGS T-score alone
      with clinical factors. In addition, combined T-score has better sensitivity and
      specificity in predicting incidence fractures than FN BMD alone. This study is
      the first study to compare the predictive ability of HGS and BMD. We showed that
      HGS is an independent risk factor for major clinical fractures. Compared with
      using FN BMD T-score of -2.5 alone, HGS alone has a comparable predictive power
      to BMD, and the combined T-score may be useful to identify extra subjects at risk
      of clinical fractures with improved specificity.

PMID- 21853265
TI  - Gut microbiota of healthy elderly NSAID users is selectively modified with the
      administration of Lactobacillus acidophilus NCFM and lactitol.
AB  - Ageing changes gut microbiota composition and alters immune system function.
      Probiotics, prebiotics and synbiotics may improve the health status of elderly
      individuals by modifying the intestinal environment and the microbiota
      composition, and by stimulating the immune system. In this work, we studied the
      effects of synbiotic supplementation on the gut microbiota of healthy elderly
      volunteers. Fifty-one elders were randomly assigned to consume either a synbiotic
      dietary supplement or a placebo in addition to their usual diet for a 2-week
      period. The synbiotic product consisted of the probiotic Lactobacillus
      acidophilus NCFM and the prebiotic lactitol and was ingested twice a day, with a
      total daily dose of 10 g lactitol and 2 * 10(10) cells of probiotic bacteria.
      Before, during and after the intervention period fecal quantities of six
      phylogenetic bacterial groups were determined using quantitative PCR, and
      relative changes in total microbiota composition were assessed by percent guanine
      plus-cytosine profiling. The microbiota profiles showed certain relative changes
      within the microbial community, and indicated an increase of bifidobacteria
      levels during synbiotic supplementation. Quantification by PCR confirmed the in
      changes in the microbiota composition; for example increases in total levels of
      endogenous bifidobacteria and lactobacilli were recorded. Throughout the 6-week
      study period there was a decrease unrelated to intervention in the Blautia
      coccoides-Eubacterium rectale bacterial group levels and Clostridium cluster
      XIVab levels, but this decrease appeared to be halted during the synbiotic
      intervention. In conclusion, putatively beneficial changes in microbiota were
      observed in the elderly subjects supplemented with the synbiotic product.

PMID- 21853266
TI  - Infanticide by a male spectral tarsier (Tarsius spectrum).
AB  - As part of a long-term field study on the behavioral ecology and conservation of
      a population of spectral tarsiers (Tarsius spectrum) in Tangkoko Nature Reserve,
      Sulawesi, Indonesia, I observed the first known instance of infanticide in this
      species. A young infant was killed by a neighboring male. Neither the
      epiphenomenal aggression hypothesis, social pathology hypothesis, nutritive
      benefits of cannibalism hypothesis, nor sexual selection hypothesis are supported
      by this observation. The only hypothesis that could not be rejected outright, on
      the basis of this single observation, was the competition for limited resources
      hypothesis.

PMID- 21853268
TI  - MicroRNA-132 targets HB-EGF upon IgE-mediated activation in murine and human mast
      cells.
AB  - MicroRNAs provide an additional layer in the regulation of gene expression acting
      as repressors with several targets at the posttranscriptional level. This study
      describes microRNA expression patterns during differentiation and activation of
      mast cells. The expression levels of 567 different mouse miRNAs were compared by
      microarray between c-Kit+ committed progenitors, mucosal mast cells, resting and
      IgE-crosslinked BMMCs in vitro. The strongest upregulation of miR-132 upon IgE
      mediated activation was validated in human cord blood-derived mast cells as well.
      HB-EGF growth factor also upregulated upon activation and was ranked high by more
      prediction algorithms. Co-transfection of miR-132 mimicking precursor and the
      3'UTR of human Hbegf-containing luciferase vector proves that the predicted
      binding site is functional. In line with this, neutralization of miR-132 by anti
      miR inhibitor leads to sustained production of HB-EGF protein in activated mast
      cells. Our data provide a novel example for negative regulation of a growth
      factor by an upregulated miRNA.

PMID- 21853271
TI  - Prevention of cytarabine-induced kerato-conjunctivitis by eye rinse in patients
      receiving high-dose cytarabine and total body irradiation as a conditioning for
      hematopoietic stem cell transplantation.
AB  - We previously reported a high incidence of kerato-conjunctivitis in patients
      receiving high-dose cytarabine following total body irradiation (TBI) as a
      conditioning for hematopoietic stem cell transplantation (HSCT) even on
      prophylaxis with topical corticosteroid. This study aimed to evaluate whether
      addition of eye rinse, which was designed to remove cytarabine from ocular
      surface, further reduces the incidence of kerato-conjunctivitis in the same
      setting. Seventy-six patients receiving cytarabine at a dose of 3 g/m(2) every 12
      h for 4 days after receiving TBI (12 Gy) as conditioning for HSCT were evaluated.
      All patients received betamethasone sodium phosphate eye drops. Twenty-three
      patients were further instructed to rinse their eyes with sterile saline every 10
      15 min during and for two additional hours after the completion of each
      cytarabine infusion. Among 23 patients with eye rinse, Grades 2-3 and 1-3 kerato
      conjunctivitis were observed in 4 (17.4%) and 5 patients (21.7%), respectively.
      These incidences were significantly lower than those [35 (66.0%) and 41 (77.4%)]
      observed in 53 patients without eye rinse (P < 0.001 and P < 0.00001,
      respectively). These results strongly suggest that eye rinse effectively reduces
      the incidence and severity of cytarabine-induced kerato-conjunctivitis in HSCT
      recipients who receive high-dose cytarabine following TBI.

PMID- 21853269
TI  - An anatomic study of the interspinous space of the lumbosacral spine.
AB  - PURPOSE: The purpose of this study is to quantify the interspinous anatomy at the
      L4/5 and L5/S1 levels. METHODS: One hundred reconstructed computer tomography
      scans of the lumbosacral spine were reviewed by two separate surgeons. Data were
      collected from the midline sagittal reconstructed image at the L4-5 and L5-S1
      levels. Measurements obtained included the disc angle, anterior and posterior
      disc height, and maximum interspinous space in both the anterior-posterior and
      cephalad-caudal directions. The disc height and disc angle were correlated with
      the interspinous height. RESULTS: The mean age of the patients reviewed was 47
      years (range: 16-91; standard deviation: 20). According to our data population,
      the average length of the interspinous space was larger at the L4-5 level (13 mm)
      than the L5-S1 level (9 mm). The interspinous height was similar between the two
      levels. A poor correlation existed between the disc height or disc angle and the
      interspinous height. There was no correlation between measurements and age.
      CONCLUSIONS: The interspinous space available, as defined by computer tomography,
      at the L5/S1 level, is less able to accommodate current interspinous devices
      compared to the adjacent L4/5 level. The limiting factor is the length of the
      sacral part of the L5-S1 interspinous space.

PMID- 21853272
TI  - Crop demand of manganese.
AB  - The objectives of this study were to evaluate some of the popular rotation crops
      grown in Hungary for tolerance to low external Mn(2+) levels and to determine the
      critical tissue concentration of Mn(2+) deficiency during early stages of growth.
      The minimum Mn(2+) concentration required in soil nutrient contents was 42.5 mg
      kg(-1) for sunflower, 24.3 mg kg(-1) for tobacco and 10.2 mg kg(-1) for
      triticale. Sunflower, tobacco and triticale achieved optimum growth at 48.0-65.0
      mg Mn(2+) kg(-1), 24.9-32.1 mg Mn( n+) kg(-1) and 28.7 to 29.6 mg Mn(2+) kg(-1),
      respectively. Critical shoot Mn(2+) concentration at early stages of growth was
      53.6 mg kg(-1) in sunflower, 458.0 mg kg(-1) in tobacco and 193.8 mg kg(-1) in
      triticale. Our results demonstrate that the tolerance to low external Mn(2+)
      (triticale: <30.2 mg kg(-1); sunflower: <56.2 mg kg(-1); tobacco: <69.3 mg kg(
      1)) and the critical tissue Mn(2+) levels for deficiency varied significantly
      between crop species tested.

PMID- 21853273
TI  - Effects of non-esterified fatty acids on the gluconeogenesis in bovine
      hepatocytes.
AB  - Dairy cows experience an increased demand for glucose to support milk production.
      However, negative energy balance is a common condition in peripartum cows. In
      response, fat mobilization provides non-esterified fatty acids (NEFAs) for
      oxidation in the liver to generate ATP. To investigate the effects of NEFAs on
      gluconeogenesis, the expression and enzyme activity of pyruvate carboxylase (PC)
      and phosphoenolpyruvate carboxylase (PEPCK) in cultured bovine hepatocytes were
      evaluated by quantitative polymerase chain reaction and spectrophotometry,
      respectively. The results showed that PC and PEPCK mRNA levels were marked
      decreased when the NEFAs concentrations exceeded 0.5 and 1.5 mmol/l,
      respectively. The PC and PEPCK enzyme activity showed significantly decreased
      when the NEFAs concentrations exceeded 1.5 and 0.5 mmol/l, respectively. These
      findings indicate that high circulating levels of NEFAs inhibit hepatocyte
      gluconeogenesis, thereby promoting negative energy balance.

PMID- 21853274
TI  - Shotgun proteomics and network analysis of ubiquitin-related proteins from human
      breast carcinoma epithelial cells.
AB  - Protein ubiquitination via the covalent attachment of ubiquitin (Ub) plays an
      important role in the regulation of the stability, function or localization of
      multiple proteins in eukaryotic cells. Comprehensive investigation of the
      proteomics related to ubiquitination will gain the insight into the Ub-mediated
      regulatory mechanism. In the present study, the combination of polyUb affinity
      purification, SDS-PAGE separation, and liquid chromatography-tandem mass
      spectrometry analysis (GeLC-MS/MS) was employed to analyze the Ub-related
      proteins in human MDA-MB-231 breast carcinoma epithelial cells after treatment
      with the proteasome inhibitor MG132. A total of 260 non-redundant Ub-related
      proteins were identified from the cells. These proteins were shown to be involved
      in a host of critical cellular functions and processes, including transcription,
      translation, Ub-proteasome pathway, cell cycle, heat shock response, transport,
      etc. The interaction network analysis by STRING indicated that the identified Ub
      related proteins formed eleven clusters, the three most highly ranked network
      clusters were mainly involved in protein translation, RNA transcription and
      processing, and Ub-proteasome pathway, suggesting that there were obvious
      ubiquitination-mediated alternations in gene expression of human MDA-MB-231
      cells. The proteomic profiling and their interaction network analysis in this
      study would help to our systematic understanding of the Ub-related cellular
      protein functions and the related biological processes in human disease tissue
      cells.

PMID- 21853275
TI  - NFBD1/MDC1 is a protein of oncogenic potential in human cervical cancer.
AB  - A large nuclear protein of 2089 amino acids, NFBD1/MDC1 has recently been
      implicated in tumorigenesis and tumor growth. In this study, we investigated its
      expression in cervical cancers and explored its function using gene knockdown
      approaches. We report here that NFBD1 expression is substantial increased in 24
      of 39 cases (61.5%) of cervical cancer tissues at the mRNA level and in 35 of 60
      cases (58.3%) at the protein level compared with the case matched normal tissues.
      Tumors with higher grade of malignancy tend to have higher levels of NFBD1
      expression. By infecting cells with retroviruses expressing NFBD1 shRNA, we
      successfully knocked down NFBD1 expression in cervical cancer cell lines HeLa,
      SiHa, and CaSki. NFBD1 knockdown cells display significant growth inhibition,
      cell cycle arrest, higher apoptotic rate, and enhanced sensitivity to adriamycin.
      Furthermore, NFBD1 knockdown also inhibits the growth of HeLa cells in nude mice.
      Western blot analyses further revealed that NFBD1 knockdown induced Bax, Puma,
      and Noxa while down-regulating Bcl-2; it also up-regulated cytochrome C and
      activated caspases 3 and 9. Therefore, the function of NFBD1 may be involved in
      the CDC25C-CyclinB1/CDC2 pathway at the G2/M checkpoint, and the cytochrome
      C/caspase 3 apoptotic pathway. Since expression of NFBD1 seems to be related to
      the oncogenic potential of cervical cancer, and suppression of its expression can
      inhibit cancer cell growth both in vitro and in vivo, NFBD1 may be a potential
      therapeutic target in human cervical cancer.

PMID- 21853276
TI  - Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated
      from normal human and osteoarthritis patients.
AB  - The aims of the study were to show the direct effect of nicotine with different
      concentrations (0, 25, 50, and 100 ng/ml) on chondrocytes isolated from normal
      human and osteoarthritis patients, respectively. Microscopic observation was
      performed during the culture with an inverted microscope. Methyl thiazolyl
      tetrazolium (MTT) assay method was adopted to observe the influence of nicotine
      on the proliferation of chondrocytes, and real-time PCR and ELISA were used to
      assay the mRNA and protein expression of type II collagen and aggrecan,
      respectively. We discovered that the OA chondrocytes were similar to fibroblasts
      in shape and grow slower than normal chondrocytes. The proliferation of the two
      kinds of chondrocytes was increased in a concentration-dependent manner and in a
      time-dependent manner (P<0.05). Also, we found that the mRNA level of type II
      collagen were upregulated under 25-100 ng/ml nicotine doses both in the two kinds
      of chondrocytes compared with control. The expression of protein levels of type
      II collagen were synthesized in line with the increase in mRNA. No effect was
      observed on aggrecan synthesis with any nicotine dose. We concluded that nicotine
      has the same effect on both chondrocytes, obtained either from osteoarthritis
      patients or from normal human, and the positive effect of smoking in OA may
      relate to the alteration in metabolism of chondrocytes.

PMID- 21853277
TI  - Recruitment bias in chronic pain research: whiplash as a model.
AB  - In science findings which cannot be extrapolated to other settings are of little
      value. Recruitment methods vary widely across chronic whiplash studies, but it
      remains unclear whether this generates recruitment bias. The present study aimed
      to examine whether the recruitment method accounts for differences in health
      status, social support, and personality traits in patients with chronic whiplash
      associated disorders (WAD). Two different recruitment methods were compared:
      recruiting patients through a local whiplash patient support group (group 1) and
      local hospital emergency department (group 2). The participants (n=118) filled in
      a set of questionnaires: the Neck Disability Index, Medical Outcome Study Short
      Form General Health Survey, Anamnestic Comparative Self-Assessment measure of
      overall well-being, Symptom Checklist-90, Dutch Personality Questionnaire, and
      the Social Support List. The recruitment method (either through the local
      emergency department or patient support group) accounted for the differences in
      insufficiency, somatization, disability, quality of life, self-satisfaction, and
      dominance (all p values <.01). The recruitment methods generated chronic WAD
      patients comparable for psychoneurotism, social support, self-sufficiency,
      (social) inadequacy, rigidity, and resentment (p>.01). The recruitment of chronic
      WAD patients solely through patient support groups generates bias with respect to
      the various aspects of health status and personality, but not social support. In
      order to enhance the external validity of study findings, chronic WAD studies
      should combine a variety of recruitment procedures.

PMID- 21853278
TI  - Impact of musculoskeletal pain on physical function and health-related quality of
      life in a rural community in south India: a WHO-ILAR-COPCORD-BJD India study.
AB  - Musculoskeletal (MSK) pain poses a major burden on individuals and health care
      systems. Assessing its pervasive impact has broadened the horizon of treatment
      strategies. The aim of this study was to determine the prevalence of MSK pain and
      its relationship with the health-related quality of life (HRQL) in a rural
      community. Individuals (>15 years) with MSK pain were identified by house-house
      survey from a population of 6,763 individuals. HRQL was assessed using the
      validated 'Modified Indian HAQ (CRD - Pune)', translated into regional language.
      Moderate and severe health assessment questionnaire disability index (HAQ-DI)
      scores were considered significant. Details regarding the impact of pain on their
      personal, family and social life were also studied. All individuals with MSK pain
      were evaluated clinically by a medical team and HAQ-DI was compared in different
      groups of disorders. Prevalence of MSK pain in the community (mean age, 52 +/-
      15.8 years) was 26.08% (95% CI 25.03-27.13). About 8% of the respondents
      reporting MSK pain had to stop work and 4% had chronic depression. A significant
      HAQ-DI was scored by 31% subjects. Level of education and intensity of work had
      significant associations with HRQL. Among the clinical diagnoses, non-specific
      MSK pain also scored a high HAQ-DI. MSK pain, both due to specific and non
      specific disorders, showed an important impact on HRQL in this community study.
      Combined with ascertainment of risk factors and associations, this has
      implications on planning treatment and prevention. We plan to continue using HAQ
      in time to monitor the community.

PMID- 21853279
TI  - Restoring ecological integrity in highly regulated rivers: the role of baseline
      data and analytical references.
AB  - The goal of restoring ecological integrity in rivers is frequently accompanied by
      an assumption that a comparative reference reach can be identified to represent
      minimally impaired conditions. However, in many regulated rivers, no credible
      historical, morphological or process-based reference reach exists. Resilient
      restoration designs should instead be framed around naturalization, using
      multiple analytical references derived from empirically-calibrated field- and
      model-based techniques to develop an integrated ecological reference condition.
      This requires baseline data which are rarely collected despite increasing
      evidence for systematic deficiencies in restoration practice. We illustrate the
      utility of baseline data collection in restoration planning for the highly
      fragmented and regulated lower Merced River, California, USA. The restoration
      design was developed using various baseline data surveys, monitoring, and
      modeling within an adaptive management framework. Baseline data assisted in
      transforming conceptual models of ecosystem function into specific restoration
      challenges, defining analytical references of the expected relationships among
      ecological parameters required for restoration, and specifying performance
      criteria for post-project monitoring and evaluation. In this way the study is an
      example of process-based morphological restoration designed to prompt recovery of
      ecosystem processes and resilience. For the Merced River, we illustrate that
      project-specific baseline data collection is a necessary precursor in developing
      performance-based restoration designs and addressing scale-related uncertainties,
      such as whether periodic gravel augmentation will sustain bed recovery and
      whether piecemeal efforts will improve ecological integrity. Given the numerous
      impediments to full, historical, restoration in many river systems, it seems
      apparent that projects of naturalization are a critical step in reducing the
      deleterious impacts of fragmented rivers worldwide.

PMID- 21853280
TI  - Who's in charge: role clarity in a Midwestern watershed group.
AB  - Studies of collaborative watershed groups show that effective leadership is an
      important factor for success. This research uses data from in-depth interviews
      and meeting observation to qualitatively examine leadership in a Midwestern
      collaborative watershed group operating with government funding. One major
      finding was a lack of role definition for volunteer steering-committee members.
      Lack of role clarity and decision-making processes led to confusion regarding
      project management authority among the group, paid project staff members, and
      agency personnel. Given the important role of government grants for funding
      projects to protect water quality, this study offers insight into leadership
      issues that groups with Clean Water Act Section 319 (h) funds may face and
      suggestions on how to resolve them.

PMID- 21853281
TI  - Urban domestic gardens: the effects of human interventions on garden composition.
AB  - Private domestic gardens contribute substantially to the biodiversity of urban
      areas and benefit human health and well-being. We previously reported a study of
      267 gardens across five cities in the United Kingdom in which variation in
      geographical and climatic factors had little bearing on the richness, diversity
      and composition of plant species. We therefore hypothesise that garden management
      is an important factor in determining garden characteristics. Here, from the same
      sample of gardens, we investigate potential associations between the uses to
      which people put their gardens, the types of management activities they
      undertake, and the characteristics of those gardens. Householders (n = 265)
      completed a questionnaire detailing various aspects of garden use and management
      activities. The majority of respondents used their gardens chiefly for
      relaxation, recreation, and eating. Fewer than one fifth included "gardening"
      amongst their garden uses even though all performed some garden management,
      suggesting that not all management activity resulted from an interest in
      gardening. Garden-watering and lawn-mowing were the most prevalent activities and
      were predictors of other types of management including weeding, vegetation
      cutting, leaf-collection, and dead-heading flowers. A number of these activities
      were associated with one another, the richness and composition of plant species,
      and the number of land uses in gardens. However, relationships between management
      activities and the amount of tall vegetation were less consistent, and garden
      management appeared to be independent of garden area. More species of amphibians,
      birds, and mammals were observed in gardens with ponds and in which efforts were
      made to attract wildlife, particularly by providing drinking water. This study
      supports the hypothesis that garden use and management is associated with garden
      characteristics.

PMID- 21853282
TI  - Self-reported health in urban-rural continuum: a grid-based analysis of Northern
      Finland Birth Cohort 1966.
AB  - OBJECTIVES: To evaluate the association of self-reported health with residential
      area type defined by the population density in individual's local environment
      using a population-based cohort in Finland. METHODS: Young adults of the Northern
      Finland Birth Cohort 1966 (4,201 women and 3,835 men), surveyed by a postal
      questionnaire in 1997, were linked to population density of their resident grid
      (1 km(2)) depicting different types of residential areas. Self-reported health
      was regressed on residential area type using ordinal logistic analysis, adjusting
      for psychosocial well-being, social relationships, health behaviour, education
      and residence time. RESULTS: Cumulative odds ratios (COR) for poor health were
      lowest in high-rise centres, highest in scattered settlement areas and second
      highest in transitional zones. Adjustments (especially for education and time of
      residence) reduced the CORs to insignificance except the persistently high COR
      for women in scattered settlement areas. CONCLUSION: Poor self-reported health is
      associated with individual's residential area type, with the lowest occurrence in
      high-rise centres and higher elsewhere. The difference is likely explained, at
      least partly, by a complex of psychosocial factors, possibly different for women
      and men.

PMID- 21853283
TI  - Effect of transnasal insufflation on sleep disordered breathing in acute stroke:
      a preliminary study.
AB  - BACKGROUND AND PURPOSE: Sleep disordered breathing (SDB) is frequent in acute
      stroke patients and is associated with early neurologic worsening and poor
      outcome. Although continuous positive airway pressure (CPAP) effectively treats
      SDB, compliance is low. The objective of the present study was to assess the
      tolerance and the efficacy of a continuous high-flow-rate air administered
      through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive
      method, to treat SDB in acute stroke patients. METHODS: Ten patients (age, 56.8
      +/- 10.7 years), with SDB ranging from moderate to severe (apnea-hypopnea index,
      AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8 +/- 3.7 days
      after ischemic stroke (range, 1-15 days), were selected. The night after, they
      underwent a second sleep study while receiving TNI (18 L/min). RESULTS: TNI was
      well tolerated by all patients. For the entire group, TNI decreased the AHI from
      40.4 +/- 25.7 to 30.8 +/- 25.7/h (p = 0.001) and the oxygen desaturation index
      >3% from 40.7 +/- 28.4 to 31 +/- 22.5/h (p = 0.02). All participants except one
      showed a decrease in AHI. The percentage of slow-wave sleep significantly
      increased with TNI from 16.7 +/- 8.2% to 22.3 +/- 7.4% (p = 0.01). There was also
      a trend toward a reduction in markers of sleep disruption (number of awakenings,
      arousal index). CONCLUSIONS: TNI improves SDB indices, and possibly sleep
      parameters, in stroke patients. Although these changes are modest, our findings
      suggest that TNI is a viable treatment alternative to CPAP in patients with SDB
      in the acute phase of ischemic stroke.

PMID- 21853284
TI  - Spatial and nonspatial implicit motor learning in Korsakoff's amnesia: evidence
      for selective deficits.
AB  - Patients with amnesia have deficits in declarative memory but intact memory for
      motor and perceptual skills, which suggests that explicit memory and implicit
      memory are distinct. However, the evidence that implicit motor learning is intact
      in amnesic patients is contradictory. This study investigated implicit sequence
      learning in amnesic patients with Korsakoff's syndrome (N = 20) and matched
      controls (N = 14), using the classical Serial Reaction Time Task and a newly
      developed Pattern Learning Task in which the planning and execution of the
      responses are more spatially demanding. Results showed that implicit motor
      learning occurred in both groups of participants; however, on the Pattern
      Learning Task, the percentage of errors did not increase in the Korsakoff group
      in the random test phase, which is indicative of less implicit learning. Thus,
      our findings show that the performance of patients with Korsakoff's syndrome is
      compromised on an implicit learning task with a strong spatial response
      component.

PMID- 21853285
TI  - Photographic documentation of the evolution of an optic nerve head lesion in a
      patient with retinitis pigmentosa.

PMID- 21853286
TI  - Utilization of nuclear medicine scintigraphy in Taiwan, 1997-2009.
AB  - OBJECTIVE: To analyze the utilization of nuclear medicine scintigraphy in the
      Taiwanese population within the national health-care system between 1997 and
      2009. METHODS: Based on the Taiwan's National Health Insurance Research Database
      of 1997-2009, a retrospective population-based analysis was conducted.
      Descriptive statistics and regression analysis were employed to analyze the
      frequencies and longitudinal trends in the utilization of diagnostic nuclear
      medicine procedures during the period. In addition, correlation analysis was
      applied to determine the correlated factors in the utility of nuclear medicine
      scintigraphy. RESULTS: The annual total nuclear medicine scintigraphy was
      estimated to be 256,389 on average in 1997-2009 and 11.7 per 1,000 population
      over the period. The frequency had increased by 67% over the years, from 8.2 per
      1,000 population in 1997 to 13.7 per 1,000 population in 2009. The most
      frequently performed procedures were whole-body bone scans (33.4% of total) and
      myocardial perfusion scans (29.4% of total), with 4,615 and 5,620 increments per
      year, respectively. Most patients were in the age group of 41-65 years old when
      taking examinations. In addition, male subjects were slightly more than female
      patients (51.5 vs. 48.5%). Furthermore, the frequencies of whole-body bone scans
      and PET scans were proportional to the incidences of cancers (correlation
      coefficients were 0.96 and 0.94, respectively). CONCLUSIONS: The utilization of
      nuclear medicine scintigraphy with the National Health Insurance system in Taiwan
      has been changed considerably in the past 13 years. Both whole-body bone scan and
      myocardial perfusion scan were performed most often with significantly increases.
      The trend of nuclear medicine scintigraphy may have potential impact on making
      health-care policy in Taiwan.

PMID- 21853287
TI  - The multiple phenotypes of corticobasal syndrome and corticobasal degeneration:
      implications for further study.
AB  - Corticobasal degeneration (CBD) is a complex neurodegenerative disorder which
      nomenclature of which its nomenclature and characterization continues to evolve.
      The core clinical features that have been considered characteristic of the
      disorder include progressive asymmetric rigidity and apraxia, with other findings
      suggesting additional cortical (e.g., alien limb phenomena, cortical sensory
      loss, myoclonus, and mirror movements) and basal ganglionic (e.g., bradykinesia,
      dystonia, and tremor) dysfunctions. The characteristic findings at autopsy are
      asymmetric cortical atrophy that is typically maximal in the frontoparietal
      regions, as well as basal ganglia and nigral degeneration. Microscopically,
      abnormal accumulations of the microtubule-associated tau protein are found in
      both neurons and glia, and this disorder is now considered one of the
      "tauopathies." CBD was initially thought to represent a distinct
      clinicopathologic entity. Recent studies have shown considerable
      clinicopathologic heterogeneity, leading some to use the term "corticobasal
      syndrome" (CBS) for the constellation of findings initially considered
      characteristic of the disorder, and the term "corticobasal degeneration" for the
      histopathologic disorder. In this review, the multiple phenotypes/syndromes
      associated with CBD pathology, and multiple diseases associated with the CBS, are
      presented. The clinicopathologic heterogeneity in CBS/CBD and the implications of
      this heterogeneity on clinical practice, on understanding the focal/asymmetric
      cerebral degeneration syndromes, and on future research are all reviewed.

PMID- 21853288
TI  - Variant in the 3' region of SNCA associated with Parkinson's disease and serum
      alpha-synuclein levels.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder.
      The presence of Lewy bodies is a major pathological change of PD. alpha-synuclein
      is the main component of Lewy bodies and is encoded by the SNCA gene. Mutations
      in the SNCA gene mainly result in rare familial forms of PD, while genetic
      variability in the SNCA gene modulates susceptibility to sporadic PD. Recent
      studies have suggested that levels of alpha-synuclein in extracellular biological
      fluid are associated with PD and implicated alpha-synuclein as a potential
      biomarker for PD diagnosis and severity. We studied serum alpha-synuclein
      concentration and two polymorphic variants of SNCA (Rep1 and rs11931074) in 110
      sporadic PD patients and 136 controls. We further explored the influence of the
      two polymorphisms on the expression levels of serum alpha-synuclein. Soluble
      alpha-synuclein was detected in serum in all subjects, with no statistically
      significant difference between PD patients and controls (p = 0.611). Different
      Rep1 alleles and genotypes did not influence the expression of serum alpha
      synuclein. The frequency of allele T of rs11931074 was significantly elevated in
      PD patients (p = 0.041), and was correlated with decreased serum alpha-synuclein
      in both dominant (p = 0.011) and additive (p = 0.008) models of association.

PMID- 21853289
TI  - A silent follicle-stimulating hormone-producing pituitary adenoma in a teenage
      male.
AB  - An 18-year-old male was referred to Toranomon Hospital seeking reoperation for
      recurrent clinically nonfunctioning pituitary adenoma. A pituitary macroadenoma
      was first suspected at age 15 due to intractable headaches. Endocrine data were
      unremarkable except slightly elevated serum follicle-stimulating hormone (FSH).
      Transsphenoidal surgery done at another hospital achieved partial tumor removal
      but the remaining tumor regrew 2 years after surgery. The recurrent tumor was
      completely and selectively removed on repeat surgery at Toranomon Hospital.
      Pathological examination confirmed a silent FSH-producing pituitary adenoma.
      Forty-five patients less than 20 years old underwent transsphenoidal surgery for
      pituitary adenoma at Toranomon Hospital between 1993 and 2010. Of the 45
      patients, 36 (80.0%) had clinically functioning adenomas and the other 9 (20.0%)
      had clinically non-functioning adenomas. No patients, other than the present
      case, had a silent gonadotroph adenoma. In contrast, among 579 patients over 20
      years old undergoing surgery for nonfunctioning pituitary adenomas between 2006
      and 2010 at Toranomon Hospital, 304 (52.3%) had silent gonadotroph adenomas.
      Gonadotroph adenomas are more common with aging: for example, 37 (61.7%) of 60
      patients more than 70 years old at the time of operation had gonadotroph
      adenomas. In conclusion, gonadotroph adenomas, especially silent gonadotroph
      adenomas, are extremely rare in childhood and adolescence.

PMID- 21853290
TI  - Effect of grapefruit juice on the pharmacokinetics of tolvaptan, a non-peptide
      arginine vasopressin antagonist, in healthy subjects.
AB  - PURPOSE: Tolvaptan is a selective vasopressin V2 receptor antagonist that can be
      given orally once daily for treatment of clinically significant hypervolemic and
      euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite
      taking other diuretics (Japan). In vitro studies indicated that tolvaptan was a
      CYP3A4 substrate. METHODS: A single-center, randomized, crossover trial of 60-mg
      tolvaptan with 240 mL of water or with 240 mL of reconstituted grapefruit juice
      (washout period of 72 h between doses) was conducted in 20 healthy subjects.
      Blood samples for tolvaptan plasma concentrations were obtained for 48 h
      postdose. RESULTS: All subjects completed the trial. Following co-administration
      with grapefruit juice, tolvaptan concentrations were elevated compared with
      tolvaptan alone for only 16 h postdose; consequently, the mean elimination half
      life of tolvaptan was unchanged, 5.7 vs 5.1 h respectively. The mean maximal
      plasma concentration (C(max)) and the area under the curve (AUC(infinity)) of
      tolvaptan were increased 1.86- and 1.56-fold respectively when co-administered
      with grapefruit juice. CONCLUSIONS: It appears that grapefruit juice increases
      the bioavailability of tolvaptan, but does not affect its systemic elimination.
      The adverse event profile was consistent with the aquaretic effect of tolvaptan
      as urinary frequency, thirst, and dry mouth were the most frequently reported
      events.

PMID- 21853291
TI  - The role of the elastic fiber system in the pathogenesis of osteoarthritis and
      knee joint laxity.
AB  - Osteoarthritis (OA) is a disease of synovial joints in which all articular
      structures are affected. Evidence suggests that a decreased density in the
      elastic fiber concentration of the knee capsule is associated with joint
      hypermobility, a condition associated with OA. However, there is no study that
      shows a direct relationship between the elastic fiber system and knee OA. The
      purpose of this study is to determine if there is a correlation between the
      elastic fiber density in medial (MCL) and lateral (LCL) collateral ligaments and
      the severity of OA. The elastic fiber concentration in MCL and LCL were examined
      in cadaver knees (n = 10; 4 M, 6 F). The elastic fiber density, measured as the
      concentration of elastic fibers per unit area, was correlated with the severity
      of OA, which was graded on a 0-16 scale using histologic and macroscopic markers.
      Among all subjects, elastic fiber concentrations between MCL (mean 15.49% +/-
      2.49) and LCL (mean 13.93 +/- 3.63) showed a significant difference (P = 0.023).
      There were no inter-gender differences between the elastic fiber concentration in
      either MCL or LCL. Among all subjects, the severity of OA was found to be
      correlated negatively with the elastic fiber concentration in both MCL (r = 
      0.693, P <= 0.05) and LCL (r = -0.718, P <= 0.05). This is the first study to
      show a correlation between the elastic fiber system and knee OA.

PMID- 21853292
TI  - The effect of domestic preparation of some potato products on acrylamide content.
AB  - The influence that food heating has on the concentration of acrylamide in home
      cooked potato dishes prepared by high-temperature, such as pan-frying, deep
      frying, roasting and microwave heating was analyzed. The experiment was performed
      with commercially available deep-frozen par-fried French fries and deep-frozen
      par-fried potato products other than French fries (cubes, wedges, noisettes,
      pancakes). Acrylamide was found in all deep-frozen par-fried French fries and
      other deep-frozen par-fried potato products before domestic preparation. The mean
      level of acrylamide content in all frozen potato products before preparation was
      found to be 322 MUg/kg. Potato products were then prepared at 180  degrees C for
      3 min and at 220  degrees C for 10 min. After domestic preparation (roasting, pan
      frying, deep-frying and microwave heating) it was found that the level of
      acrylamide in all products increased. Acrylamide content in the analyzed samples
      significantly increased as the temperature and time of processing increased. The
      statistical analysis showed significant differences (P < 0.05) for acrylamide
      content as a function of food preparation. The level of acrylamide increased with
      the increased heating temperature and heating time. Additionally, the preparation
      method of roasting was significantly lower in acrylamide content (P < 0.05) than
      the preparation method of microwaving although both preparation methods used the
      same conditions (time and temperature). These results suggest that microwaving
      might be more favourable to the formation of acrylamide than conventional heating
      methods, such as roasting.

PMID- 21853293
TI  - Tubular nephrotoxicity induced by docetaxel in non-small-cell lung cancer
      patients.
AB  - Renal dysfunction is a characteristic of many patients with cancer; however, a
      standard therapy has not been established for stage III or IV non-small-cell lung
      cancer (NSCLC) complicated with chronic renal failure. Docetaxel has a proven
      significant activity against NSCLC. This agent is predominantly eliminated by
      hepatobiliary extraction and is safe in patients with renal failure, including
      dialysis patients. Docetaxel is, thus, a therapeutic option in that patient
      population. Here, we report acute tubular nephrotoxicity secondary to docetaxel
      in NSCLC patients, even in patients with normal renal function. Little is known
      about tubular nephrotoxicity induced by docetaxel; however, oncologists should be
      aware of its possibility.

PMID- 21853294
TI  - Male osteoporosis: epidemiology and the pathogenesis of aging bones.
AB  - Osteoporosis in men is an overlooked yet increasingly important clinical problem
      that, historically, has not received the same degree of awareness as with women.
      Epidemiologic studies demonstrate that male osteoporosis contributes
      significantly to the burden of osteoporotic fractures, especially among the aging
      population. In particular, men have increased morbidity and mortality associated
      with osteoporotic fractures compared with women. Diagnostic challenges of male
      osteoporosis include lack of consensus about appropriate reference ranges for
      identifying osteoporosis in men, and the lack of a fracture assessment tool in
      men necessary to identify those individuals at risk. Compared with women, changes
      that occur in the aging male skeleton include trabecular thinning, greater
      endocortical expansion, ongoing periosteal apposition with greater bending
      strength, and preserved minimum moment of inertia. Overall, men have less
      microstructural damage with aging and beneficial geometric adaptations that lead
      to stronger bones, compared with women, and thus their overall lower risk of
      fractures.

PMID- 21853295
TI  - Mendel: a simple excel workbook to compare the observed and expected
      distributions of genotypes/phenotypes in transgenic and knockout mouse crosses
      involving up to three unlinked loci by means of a chi2 test.
AB  - The analysis of transgenic and knockout mice always involves the establishment of
      matings with individuals carrying different loci, segregating independently,
      whose presence is expected among the progeny, according to a Mendelian
      distribution. The appearance of distorted inheritance ratios suggests the
      existence of unexpected lethal or sub-lethal phenotypes associated with some
      genotypes. These situations are common in a number of cases, including: testing
      transgenic founder mice for germ-line transmission of their transgenes; setting
      up heterozygous crosses to obtain homozygous individuals, both for transgenic and
      knockout mice; establishing matings between floxed mouse lines and suitable cre
      transgenic mouse lines, etc. The Pearson's chi(2) test can be used to assess the
      significance of the observed frequencies of genotypes/phenotypes in relation to
      the expected values, in order to determine whether the observed cases fit the
      expected distribution. Here, I describe a simple Excel workbook to compare the
      observed and expected distributions of genotypes/phenotypes in transgenic and
      knockout mouse crosses involving up to three unlinked loci by means of a chi(2)
      test. The file is freely available for download from my laboratory's web page at:
      http://www.cnb.csic.es/~montoliu/Mendel.xls .

PMID- 21853296
TI  - High level accumulation of gamma linolenic acid (C18:3Delta6.9,12 cis) in
      transgenic safflower (Carthamus tinctorius) seeds.
AB  - Gamma linolenic acid (GLA; C18:3Delta6,9,12 cis), also known as gamma-Linolenic
      acid, is an important essential fatty acid precursor for the synthesis of very
      long chain polyunsaturated fatty acids and important pathways involved in human
      health. GLA is synthesized from linoleic acid (LA; C18:2Delta9,12 cis) by
      endoplasmic reticulum associated Delta6-desaturase activity. Currently sources of
      GLA are limited to a small number of plant species with poor agronomic
      properties, and therefore an economical and abundant commercial source of GLA in
      an existing crop is highly desirable. To this end, the seed oil of a high LA
      cultivated species of safflower (Carthamus tinctorius) was modified by
      transformation with Delta6-desaturase from Saprolegnia diclina resulting in
      levels exceeding 70% (v/v) of GLA. Levels around 50% (v/v) of GLA in seed oil was
      achieved when Delta12-/Delta6-desaturases from Mortierella alpina was over
      expressed in safflower cultivars with either a high LA or high oleic (OA;
      C18:1Delta9 cis) background. The differences in the overall levels of GLA suggest
      the accumulation of the novel fatty acid was not limited by a lack of
      incorporation into the triacylgylcerol backbone (>66% GLA achieved), or
      correlated with gene dosage (GLA levels independent of gene copy number), but
      rather reflected the differences in Delta6-desaturase activity from the two
      sources. To date, these represent the highest accumulation levels of a newly
      introduced fatty acid in a transgenic crop. Events from these studies have been
      propagated and recently received FDA approval for commercialization as
      SonovaTM400.

PMID- 21853298
TI  - Practice and place in twentieth-century field biology:  a comment.

PMID- 21853297
TI  - Do we really know why diabetes remits after gastric bypass surgery?
AB  - Roux-en-Y gastric bypass surgery (GBP) results in 30-40% sustained weight loss
      and improved type 2 diabetes in up to 80% of patients. The relative contribution
      of the gut neuroendocrine changes after GBP versus the weight loss has not been
      fully elucidated. There are clear differences between weight loss by GBP and by
      dietary intervention or gastric banding. One of them is the enhanced post
      prandial release of incretin hormones and the recovery of the incretin effect on
      insulin secretion after GBP, not seen after diet-induced weight loss. The
      favorable changes in incretin hormones after GBP result in recovery of the early
      phase insulin secretion and lower post-prandial glucose levels during oral
      glucose administration. The enhanced incretin response may be related to the
      neuroglycopenia post-GBP. In parallel with changes of glucose metabolism, a
      larger decrease of circulating branched-chain amino acids in relation to improved
      insulin sensitivity and insulin secretion is observed after GBP compared to diet.
      The mechanisms of the rapid and longterm endocrine and metabolic changes after
      GBP are not fully elucidated. Changes in rate of eating, gastric emptying,
      nutrient absorption and sensing, bile acid metabolism, and microbiota may all be
      important. Understanding the mechanisms by which incretin release is exaggerated
      post-prandially after GBP may help develop new less invasive treatment options
      for obesity and diabetes. Equally important would be to identify biological
      predictors of success or failure and to understand the mechanisms of weight
      regain and/or diabetes relapse.

PMID- 21853299
TI  - A simple and safe technique for trocar positioning in vesicoscopic ureteric
      reimplantation.
AB  - PURPOSE: Anchoring of the urinary bladder to the anterior abdominal wall is
      essential to prevent perivesical gas leak and dislodgement of trocar. Existing
      techniques have the risk of going through the peritoneal cavity and injuring the
      bowel. Our aim was to find a safe technique to anchor the bladder wall to the
      abdominal wall. MATERIALS AND METHODS: Nineteen cases were studied prospectively.
      A curved urethral dilator was introduced and made to point on the anterior
      abdominal wall. Abdominal wall was incised over the tip of the dilator till the
      bladder was seen which was then sutured to the anterior abdominal wall. The
      bladder was then incised and the trocars were railroaded on the dilator into the
      bladder. Cohen's reimplantation was then done. RESULTS: Out of the 19 cases,
      conversion to open was done in two early cases. In one case, the trocar got
      pulled out, but was easily reintroduced. Mean operating time was 210 min. Mean
      follow up was 20.9 months. There was a resolution of reflux in 13, reduction in
      the grade of reflux in 1 and no failures. In five cases, post op MCU is awaited.
      CONCLUSION: This technique of fixing the bladder to the anterior abdominal wall
      is safe and easy to perform. It is recommended while doing vesicoscopic
      reimplantation.

PMID- 21853300
TI  - Surgical repair of recurrent prolapse after LeFort colpocleisis.
AB  - Recurrent pelvic organ prolapse occurs rarely after obliterative procedures. The
      optimal surgical approach for therapy is unknown. We describe a case of recurrent
      prolapse after LeFort colpocleisis. The patient presented with stage III prolapse
      through the lateral vaginal channel. At surgery, the prolapse was repaired using
      a modified repeat colpocleisis and repeat perineorrhaphy. Transvaginal revision
      via modified repeat colpocleisis should be considered for treatment of recurrent
      pelvic organ prolapse after LeFort colpocleisis.

PMID- 21853301
TI  - Upregulation of B7-H1 expression is associated with macrophage infiltration in
      hepatocellular carcinomas.
AB  - The overexpression of B7-H1 in hepatocellular carcinoma (HCC) mediates HCC immune
      escape and obstructs the immunotherapy based on tumor-specific CD8+ T cells.
      Tumor-associated macrophages (TAM) are a major component of cancer-related
      inflammation and play a central role in tumor promotion. To classify the
      mechanism underlying the overexpression of B7-H1 in HCC, we examined B7-H1
      expression and TAM infiltration in 63 cases of human HCC samples using
      immunohistochemistry method and found that B7-H1 overexpression was associated
      with TAM infiltration in HCC tissues. Furthermore, B7-H1 expression was
      upregulated at both mRNA level and protein level in HCC cells (BEL-7402 and SMMC
      7721) cocultured with macrophages in a transwell system. The upregulation of B7
      H1 expression induced by macrophage was inhibited by blocking NF-kappaB or STAT3
      signal pathways. These results suggest that overexpression of B7-H1 in HCC may be
      induced by inflammatory microenvironment involving macrophages and imply that
      anti-inflammation therapy might be preventive for immune escape and assistant for
      immunotherapy of HCC.

PMID- 21853302
TI  - Interleukin 6 mediates production of interleukin 10 in metastatic melanoma.
AB  - We previously reported that substantial amounts of IL-10, an immunomodulatory
      cytokine, are produced by cell suspensions of fresh human metastatic melanoma
      tissues. Production diminished with continuous culturing of cells, which suggests
      a pivotal interactive role between melanoma cells and the tumor microenvironment.
      In this study, we found that the culture media obtained from LPS-stimulated
      peripheral blood mononuclear cells induced IL-10 production by metastatic
      melanoma cells. Of the multiple cytokines present in the conditioned culture
      media, IL-6 was identified as the inducer of IL-10 production. A neutralizing
      antibody against IL-6 completely blocked the conditioned medium-induced IL-10
      production. Metastatic melanoma cells that constitutively produce low amount of
      IL-10 increased IL-10 production in response to recombinant human IL-6 in a dose
      dependent fashion. The response to exogenously added IL-6 was less significant in
      melanoma cells that produced high amounts of IL-6, probably due to pre-existing
      autocrine stimulation of IL-10 by endogenous IL-6. On the other hand, metastatic
      melanoma cells that do not constitutively produce IL-10 protein did not respond
      to exogenous IL-6. In IL-6-responsive melanoma cells, IL-6 increased STAT3
      phosphorylation and inhibition of STAT3 signaling using siRNA or inhibitors for
      JAKs diminished IL-6-induced IL-10 production. In addition, inhibition of MEK and
      PI3K, but not mTOR, interfered with IL-10 production. Taken together, the data
      suggest that blocking of these signals leading to IL-10 production is a potential
      strategy to enhance an anti-melanoma immune response in metastatic melanoma.

PMID- 21853303
TI  - Wikipedia: A good address for neuroradiologists?

PMID- 21853305
TI  - Comment on: A cost-utility analysis of mechanical thrombectomy as an adjunct of
      intravenous tissue-type plasminogen activator for acute large-vessel ischemic
      stroke: Kim AS, Nguyen-Huynh M, Johnston SC. Stroke 2011;42:2013-2018.

PMID- 21853306
TI  - Age-related changes in cardio-respiratory responses and muscular performance
      following an Olympic triathlon in well-trained triathletes.
AB  - The aim of the present study was to compare the maximal isometric torque and
      cardio-respiratory parameters in well-trained young and master triathletes prior
      to and following an Olympic distance triathlon. One day before and 24 h following
      the event, participants performed three maximum voluntary isometric knee
      extensions and flexions and an incremental running test on a treadmill to
      determine the maximal isometric torque, maximal oxygen uptake VO(2max), speed at
      VO(2max) (vVO(2)max), speed at ventilatory thresholds (VT1 and VT2) and
      submaximal running economy. Prior to the event VO(2max), vVO(2)max, speed at
      ventilatory thresholds and running economy were significantly lower in master
      athletes, but maximal voluntary torque was similar between the groups. 24 h
      following the race, a similar significant decrease in VO(2max) (-3.1% in masters,
      and -6.2% in young, p < 0.05), and vVO(2)max (-9.5% in masters, and -5.6% in
      young, p < 0.05) was observed in both the groups. The speed at VT2 significantly
      decreased only in master athletes (-8.3%, p < 0.05), while no change was recorded
      in maximal voluntary torque or submaximal running economy following the event.
      The results indicate that for well-trained subjects, the overall relative
      exercise intensity during an Olympic distance triathlon and the fatigue 24 h
      following the event seem to be independent of age.

PMID- 21853307
TI  - Sprinter's motor signature does not change with fatigue.
AB  - The aim of this study was to investigate human adaptations to fatigue induced by
      track sprint repetitions. Eight male sprinters were asked to run 4 * 100 m as
      quickly as possible with 3 min of recovery. Subjects were filmed (50 Hz) in order
      to measure stride length and frequency. Velocity was measured by means of radar
      (250 Hz) while contact and flight times were registered wirelessly by two
      pressure sensors (400 Hz) embedded under the insole of the subjects' shoes.
      Contact and flight times were used to calculate stiffness. In addition, blood
      samples were taken prior to warm-up, 1 min after each 100-m sprint and every 2
      min after the last repetition until a lactate peak ([BLa]) was reached. [BLa] did
      not affect mechanical and stride parameters. Inter-series ANOVA showed that
      velocity decreased significantly (-3.55%) between Repetition 1 (8.18 +/- 0.29 m
      s(-1)) and Repetition 4 (7.89 +/- 0.42 m s(-1)), while [BLa] increased from 6.74
      +/- 1.15 to 13.58 +/- 1.48 mmol l(-1) (p < 0.05). The first main result was that
      leg stiffness remained constant until Repetition 3 and then dramatically
      increased at Repetition 4, whereas vertical stiffness remained constant
      throughout all four repetitions. This behavior could be considered to be a
      neuromuscular adaptation to fatigue used by skilled athletes. The second main
      result was that velocity decreased during the second phase (30-80 m) of the
      entire 100 m. In addition, a PCA revealed three different sprint profiles
      explaining 88.2% of the total variance: the contact-time-pattern (39.46%), force
      pattern (27.96%) and stride-pattern (20.77%). Two different motor signatures were
      identified with fatigue. In the first, athletes switch from the key variable to
      another when exhausted without changing their motor behavior (during Repetition 3
      and/or Repetition 4). In the second, athletes do not change their motor behavior
      with fatigue.

PMID- 21853308
TI  - In vivo imaging of astrocytosis in Alzheimer's disease: an 11C-L-deuteriodeprenyl
      and PIB PET study.
AB  - PURPOSE: Astrocytosis is an important feature of the neuropathology of
      Alzheimer's disease (AD), yet there is currently no way of detecting this
      phenomenon in vivo. METHODS: In this study we examine the retention of the
      positron emission tomography (PET) tracer (11)C-L-deuteriodeprenyl (DED), thought
      to bind activated astrocytes, in 9 patients with moderate to severe AD compared
      with 11 healthy controls. As a measure of amyloid load, (11)C-labelled Pittsburgh
      Compound B (PIB) retention was determined. RESULTS: Results show a significantly
      higher (11)C-L-DED retention in the frontal (35.1% increase, p = 0.001), parietal
      (35.2%, p = 0.001), temporal (30.9%, p = 0.0001) and medial temporal lobes
      (22.3%, p = 0.001) in AD compared to healthy controls after blood flow
      correction. DED retention in the sensorimotor and occipital cortices, and in
      white matter and subcortical structures, did not differ between groups. There was
      a moderate but statistically significant (r = 0.492, p = 0.01) correlation
      between DED and PIB retention values. CONCLUSION: Our conclusion is that DED may
      serve as an in vivo marker for astrocytosis in AD, providing a window into
      intermediate processes between amyloidosis and neuronal loss and a means of
      monitoring immunotherapy.

PMID- 21853310
TI  - Phase I and pharmacokinetic study of nab-paclitaxel, nanoparticle albumin-bound
      paclitaxel, administered weekly to Japanese patients with solid tumors and
      metastatic breast cancer.
AB  - PURPOSE: We conducted phase I and tolerability studies to determine the maximum
      tolerated dose (MTD) and recommended dose of nab-paclitaxel when administered
      weekly with solid tumors and to evaluate the tolerability of weekly
      administration at a dose of 150 mg/m(2) with metastatic breast cancer (MBC) as a
      first-line therapy in Japanese patients. METHODS: In this phase I study, patients
      with advanced solid tumors received nab-paclitaxel at dose levels of 80-125
      mg/m(2) as 30-min infusions once a week for three weekly doses repeated every 4
      weeks. In the tolerability study, patients received 150 mg/m(2) nab-paclitaxel.
      Blood samples at the first dose of nab-paclitaxel were collected for
      pharmacokinetic analysis. RESULTS: Fifteen patients were treated for a median of
      five cycles in the phase I study. The MTD was 125 mg/m(2); the dose-limiting
      toxicity was neutropenia requiring skipping of the second or third weekly
      administration in the first cycle. In the tolerability study, six patients were
      treated for a median of six cycles; no intolerable toxicities were observed in
      the first cycle. Grade 3 sensory and motor neuropathy was observed in four and
      one patients, respectively. Ocular toxicities were observed in two patients
      (keratopathy and macular hole). Maximum paclitaxel concentration and area under
      the curve increased linearly with the dose. CONCLUSIONS: Weekly administration of
      nab-paclitaxel was well tolerated up to 100 mg/m(2) by heavily pretreated
      patients. For MBC patients, 150 mg/m(2) nab-paclitaxel as a first-line therapy
      was well tolerated. Dose reduction due to neuropathy allows multiple cycles of
      treatment.

PMID- 21853309
TI  - Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head
      and neck cancer: a systematic review and meta-analysis.
AB  - PURPOSE: Our objective was to conduct a systematic review and meta-analysis of
      studies assessing the diagnostic performance of (18)F-fluorodeoxyglucose positron
      emission tomography (FDG PET) with or without computed tomography (CT) in post
      treatment response assessment and/or surveillance imaging of head and neck
      squamous cell carcinoma (HNSCC). METHODS: A systematic search of the indexed
      medical literature was done using appropriate keywords to identify relevant
      studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) were
      extracted from individual studies and combined using a random effects model to
      yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The
      impact of timing of post-treatment scan, study quality and advancements in PET
      technology was explored through meta-regression. RESULTS: A total of 51 studies
      involving 2,335 patients were included in the meta-analysis. The weighted mean
      (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG
      PET(CT) for the primary site was 79.9% (73.7-85.2%), 87.5% (85.2-89.5%), 58.6%
      (52.6-64.5%) and 95.1% (93.5-96.5%), respectively. Similar estimates for the neck
      were 72.7% (66.6-78.2%), 87.6% (85.7-89.3%), 52.1% (46.6-57.6%) and 94.5% (93.1
      95.7%), respectively. Scans done >= 12 weeks after completion of definitive
      therapy had moderately higher diagnostic accuracy on meta-regression analysis
      using time as a covariate. CONCLUSION: The overall diagnostic performance of post
      treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC
      is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high
      and a negative post-treatment scan is highly suggestive of absence of viable
      disease that can guide therapeutic decision-making. Timing of post-treatment
      imaging has a significant, though moderate impact on diagnostic accuracy.

PMID- 21853311
TI  - Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S
      1 or capecitabine) in Japanese patients with previously untreated advanced
      gastric cancer.
AB  - PURPOSE: The primary objective of this Phase I study was to assess the safety and
      tolerability of the vascular endothelial growth factor signalling inhibitor
      cediranib in combination with cisplatin plus an oral fluoropyrimidine, in
      Japanese patients with previously untreated advanced gastric cancer. METHODS:
      Patients received continuous, once-daily oral doses of cediranib 20 mg in
      combination with either cisplatin (60 mg/m(2) iv day 1) plus S-1 (40-60 mg bid,
      days 1-21) every 5 weeks for a maximum of eight cycles [Arm A]; or cisplatin (80
      mg/m(2) iv, day 1) plus capecitabine (1,000 mg/m(2) bid, days 1-14) every 3 weeks
      for a maximum of six cycles [Arm B]. In both arms, the assessment period for dose
      limiting toxicities (DLTs) was the first 21 days of cycle 1. RESULTS: Fourteen
      patients (Arm A, n = 6; Arm B, n = 8) were enrolled and received at least one
      dose of cediranib. One patient in each arm experienced a DLT (Arm A; decreased
      appetite, grade 3; Arm B, decreased appetite, fatigue and hyponatraemia, all
      grade 3). Overall, the most common adverse events were decreased appetite,
      fatigue and nausea (all n = 13 [92.9%]). Preliminary efficacy evaluation showed
      one confirmed (Arm A) and three unconfirmed (Arm A, n = 1; Arm B, n = 2) partial
      responses that were ongoing at data cut-off. CONCLUSIONS: Cediranib 20 mg/day in
      combination with cisplatin and S-1 or capecitabine was tolerable, with no new
      toxicities identified, and showed preliminary evidence of antitumour activity.

PMID- 21853312
TI  - Prognostic impact of vascular endothelial growth factor-A expression in resected
      gallbladder carcinoma.
AB  - The purpose of this study was to evaluate the value of vascular endothelial
      growth factor-A (VEGF-A) expression and other confirmed prognostic factors in
      predicting clinical outcomes after the resection of gallbladder carcinoma (GBC).
      Between January 1999 and January 2006, a total of 84 consecutive and non-selected
      patients who underwent resection for GBC were retrospectively reviewed. Of the 84
      patients studied, 45 cases (53.6%) exhibited high expression of VEGF-A and were
      placed into the high expression group. The 14 cases (16.7%) that showed no VEGF
      expression and the 25 cases (29.7%) that had lower VEGF-A levels were pooled into
      the low expression group (46.4%). There was a relationship between VEGF-A status
      and pM stage (P = 0.027) as well as histologic differentiation (P < 0.001). In
      univariate analysis by log-rank test, ECOG performance status, CA 19-9, pN stage,
      pM stage, histologic differentiation, and VEGF-A expression were significant
      prognostic factors (P = 0.015, 0.001, 0.020, <0.001, 0.040, and <0.001,
      respectively). Multivariate analysis revealed that pN status and VEGF-A
      expression maintained independent prognostic influence on overall survival (P <
      0.001 and P = 0.013, respectively). VEGF-A expression has a positive correlation
      with pM stage and histologic differentiation. pN status and VEGF-A expression
      were independent prognostic factors of overall survival in patients with resected
      GBC.

PMID- 21853313
TI  - Overexpression of osteopontin and integrin alphav in laryngeal and hypopharyngeal
      carcinomas associated with differentiation and metastasis.
AB  - PURPOSE: Osteopontin (OPN) is a secreted phosphoprotein, which functions as a
      cell attachment protein and cytokine that signals through two cell adhesion
      molecules, integrin alphavbeta3 and CD44, to regulate cancer growth and
      metastasis. The aim of this study was to investigate the expression of OPN and
      integrin alphav (ITGAV, main receptor of the OPN) in laryngeal and hypopharyngeal
      squamous cell carcinoma (LHSCC) and correlate the expression quantity with tumor
      biological behavior. METHODS: We have made a tissue microarray of LHSCC and
      detected the OPN and ITGAV expression by immunohistochemistry in the microarray.
      The expression quantity of OPN and ITGAV was determined by a professional
      pathological image processing software (Image-Pro plus 5.02), and the clinical
      significances of the expression quantity in LHSCC were analyzed. RESULTS: The
      expression quantity of OPN and ITGAV in primary and metastatic carcinomas is
      significantly higher than in normal tissues. The expression of OPN and ITGAV in
      the well-differentiated group is significantly lower than in moderately and
      poorly differentiated group; the expression quantity of OPN and ITGAV in group
      with lymph node metastasis is significantly higher than in group without lymph
      node metastasis. CONCLUSIONS: The expression of OPN and ITGAV was significantly
      influenced to the differentiation and metastasis of the LHSCC. Overexpression of
      the OPN and ITGAV may have contributed to invasion and metastasis of the LHSCC,
      and therefore, OPN and ITGAV may have value as a target for chemotherapy in LHSCC
      treatment.

PMID- 21853314
TI  - Client-related work tasks and meaning of work: results from a longitudinal study
      among eldercare workers in Denmark.
AB  - PURPOSE: To investigate the association between the perception of client-related
      work tasks and the experience of meaning of work among eldercare workers in the
      Danish eldercare sector. METHODS: We used baseline and follow-up questionnaire
      data from 3,985 female eldercare workers. The eldercare workers' perception of
      the client-related work tasks was measured by six items. Meaning of work was
      measured by a three-item scale. General linear modelling was used to investigate
      the association between the client-related work tasks at baseline and experience
      of meaning of work at follow-up adjusted for job title, type of workplace, and
      age. RESULTS: When care workers experience to have time to be flexible in the
      care provision and to be able to talk and socialize with the elderly, they are
      significantly more likely to experience meaning of work at follow-up than care
      workers who occasionally or rarely have this experience. Care workers who
      frequently experience to have to end a visit prematurely are significantly less
      likely to experience meaning of work at follow-up than care workers who rarely
      experience this. Experiences of having time to perform other than pre-planned
      tasks and to have insufficient time have little impact on experience of meaning
      of work at follow-up. CONCLUSION: This study indicates that to enhance the
      experience of meaning of work among eldercare workers, improvements of the
      relational aspects of care work, i.e. the possibilities to talk, socialize, and
      involve the elderly in the care provision, should be considered.

PMID- 21853315
TI  - Work-related allergy in medical doctors: atopy, exposure to domestic animals,
      eczema induced by common chemicals and membership of the surgical profession as
      potential risk factors.
AB  - PURPOSE: To investigate the risk factors associated with work-related allergy
      like symptoms in medical doctors. METHODS: Self-administered questionnaire survey
      and CAP test were conducted among medical school students in the 4th grade of
      their 6-year medical course in 1993-1996 and 1999-2001. Follow-up questionnaires
      were sent in 2004 to the graduates. These questionnaires enquired into personal
      and family history of allergic diseases, lifestyle, history of allergy-like
      symptoms including work-relatedness and occupational history as medical doctors.
      Relationships between allergy-like symptoms and relevant factors were evaluated
      by multivariate logistic regression analysis. RESULTS: Of 261 respondents at the
      follow-up survey, 139 (53.3%) and 54 (20.7%) had a history of any allergy-like
      symptoms and any work-related allergy-like symptoms, respectively. Female gender
      and family history of allergic diseases were significantly associated with any
      allergy-like symptoms. Personal history of allergic disease, exposure to domestic
      animals, eczema caused by rubber gloves, metallic accessories, or cosmetics
      during schooling days, and membership of the surgical profession were significant
      risk factors for work-related allergy-like symptoms. On the contrary, to work
      related allergy-like symptoms, gender, age, and smoking status were not
      significantly related, and consumption of prepared foods was inversely related.
      CONCLUSIONS: Personal history of atopy and eczema induced by common goods and the
      history of keeping domestic animals may be predictors of work-related allergy
      like symptoms in doctors. After graduation from medical school, physicians start
      with exposure to various allergens and irritants at work, which relate to work
      related allergy-like symptoms, especially for surgeons.

PMID- 21853316
TI  - ERIC-PCR genotyping of paenibacillus larvae in southern Italian honey and brood
      combs.
AB  - Given the considerable economic loss to beekeepers worldwide and the possible
      public health implications related to the presence of antibiotics in honey, an
      American Foulbrood (AFB) monitoring/prevention program for Paenibacillus larvae
      is regarded as essential. This study investigates the occurrence and distribution
      of P. larvae genotypes in honey and brood combs from Apulia (Italy). Genotyping
      of P. larvae isolates using ERIC-PCR generated a total of four different ERIC
      banding patterns (ERIC-A, ERIC-B, ERIC-C, ERIC-D), including fragments ranging
      from 200 to 3000 bp. Considering that the genotype has an influence on P. larvae
      infections and multi-genotype infections of colonies or apiaries may increase the
      complexity of P. larvae infections by influencing the type and speed of the
      development of clinical symptoms, the findings of the present study could be
      helpful for training veterinarians, bee inspector's extension staff, and
      beekeepers, thus improving the detection of AFB infections in the field.

PMID- 21853318
TI  - Neurodevelopmental outcomes of extremely low birth weight infants ventilated with
      continuous positive airway pressure vs. mechanical ventilation.
AB  - OBJECTIVE: To compare continuous positive airway pressure (CPAP) vs. traditional
      mechanical ventilation (MV) at 24 h of age as predictors of neurodevelopmental
      (ND) outcomes in extremely low birth weight (ELBW) infants at 18-22 months
      corrected gestational age (CGA). METHODS: Infants <=1000 g birth weight born from
      January 2000 through December 2006 at two hospitals at the Cincinnati site of the
      National Institute of Child Health and Human Development Neonatal Research
      Network were evaluated comparing CPAP (n = 198) vs. MV (n = 109). Primary
      outcomes included the Bayley Score of Infant Development Version II (BSID-II),
      presence of deafness, blindness, cerebral palsy, bronchopulmonary dysplasia and
      death. RESULTS: Ventilatory groups were similar in gender, rates of preterm
      prolonged rupture of membranes, antepartum hemorrhage, use of antenatal
      antibiotics, steroids, and tocolytics. Infants receiving CPAP weighed more, were
      older, were more likely to be non-Caucasian and from a singleton pregnancy.
      Infants receiving CPAP had better BSID-II scores, and lower rates of BPD and
      death. CONCLUSIONS: After adjusting for acuity differences, ventilatory strategy
      at 24 h of age independently predicts long-term neurodevelopmental outcome in
      ELBW infants.

PMID- 21853317
TI  - Two types of phytases (histidine acid phytase and beta-propeller phytase) in
      Serratia sp. TN49 from the gut of Batocera horsfieldi (coleoptera) larvae.
AB  - Microbial phytases play a major role in the mineralization of organic
      phosphorous, especially in symbiotic plants and animals. In this study, we
      identified two types of phytases in Serratia sp. TN49 that was harbored in the
      gut of Batocera horsfieldi (Coleoptera) larvae. The two phytases, an acidic
      histidine acid phosphatase (PhyH49) and an alkaline beta-propeller phytase
      (PhyB49), shared low identities with known phytases (61% at most). PhyH49 and
      PhyB49 produced in Escherichia coli exhibited maximal activities at pH 5.0 (60
      degrees C) and pH 7.5-8.0 (45 degrees C), respectively, and are complementary in
      phytate degradation over the pH range 2.0-9.0. Serratia sp. TN49 harboring both
      PhyH49 and PhyB49 might make it more adaptive to environment change,
      corresponding to the evolution trend of microorganism.

PMID- 21853319
TI  - Comparison of the effects of Er,Cr:YSGG laser and different cavity disinfection
      agents on microleakage of current adhesives.
AB  - The aim of this study was to compare the effect of the Er,Cr:YSGG laser and
      different cavity disinfection agents on microleakage of an etch-and-rinse and a
      self-etch adhesive. Class V preparations were completed on the buccal and lingual
      surfaces of 30 extracted noncarious human molars. The occlusal margin was placed
      on enamel and the gingival margin on dentin. Preparations were randomly divided
      into five experimental groups (n = 12); (1) 2% chlorhexidine gluconate (CHX), (2)
      propolis, (3) ozone, (4) Er,Cr:YSGG laser, and (5) control (no treatment). Each
      group was divided into two subgroups according to the adhesive system: etch-and
      rinse (Adper Single Bond 2), and a self-etch adhesive (All-Bond SE). The
      preparations were bulk-filled with a resin composite (Arabesk). After storage in
      distilled water for 24 h the restored teeth were subjected to thermocycling
      (1,000 cycles; 5-55 degrees C). All specimens were immersed in 0.5% basic fuchsin
      solution for 24 h and sectioned longitudinally through the centre of the
      restorations and examined under a stereomicroscope at *25 magnification. The data
      were analysed using the Kruskal-Wallis and Mann-Whitney U-tests. No difference
      was observed between the groups either on enamel or dentin when the etch-and
      rinse adhesive was used (p > 0.05). In the self-etch adhesive groups, a
      significant difference was found only between the laser group and the CHX group
      on enamel and between the propolis group and the control group on dentin (p <
      0.05). Comparing the etch-and-rinse and self-etch adhesives within each group, no
      differences were found on dentin (p > 0.05). On enamel, a statistically
      significant difference was found only in the CHX group (p < 0.05). There were no
      differences in microleakage with the laser and the different cavity disinfectant
      applications when used with etch-and-rinse adhesive. In the self-etch group there
      were differences in microleakage depending on the disinfection agent used.

PMID- 21853320
TI  - Diabetic distal symmetric polyneuropathy: effect of low-intensity laser therapy.
AB  - Low-intensity laser therapy (LILT) has been considered as a treatment modality in
      diabetic distal symmetric polyneuropathy (DSP). The aim of this study is to
      determine the effectiveness of LILT on DSP. We examined 107 subjects with type 2
      diabetes for detection of DSP using the Michigan Neuropathy Screening Instrument
      (MNSI). Seventeen subjects were eligible to be enrolled in the study. Nerve
      conduction studies (NCS) were performed in all eligible subjects as an objective
      method to confirm neuropathy. The participants received LILT three times a week
      for ten sessions. NCSs were reevaluated after completion of the treatment. The
      absolute changes in NCS parameters were considered to establish the effectiveness
      of the treatment. Baseline demographics were similar in all participants. The
      mean differences of NCV parameters were considered for comparison. At the end of
      the study, the subjects showed a significant increase in neural potential
      amplitudes (p < 0.05). This study clearly demonstrated a significant positive
      effect of LILT on improvement of nerve conduction velocity on diabetic distal
      symmetric polyneuropathy (DSP). This finding supports the therapeutic potential
      of LILT in DSP.

PMID- 21853321
TI  - Musculoskeletal: what is different in children? Being checked for cough,
      congestion, and also complaints of limping.

PMID- 21853322
TI  - Endovascular stent-graft placement for ruptured dissecting aortic aneurysm in an
      adolescent patient with systemic lupus erythematosus: case report.

PMID- 21853323
TI  - Urinary urgency: a review of its assessment as the key symptom of the overactive
      bladder syndrome.
AB  - PURPOSE: Overactive bladder (OAB) is a common condition that is associated with a
      negative impact on quality of life. Urgency is the essential symptom when making
      a diagnosis, and its effective treatment is a principal aim in OAB management.
      However, urgency has often been relatively neglected as an outcome measure in
      clinical trials. The aim of this review is, first, to describe the background to
      urgency in OAB; second, to determine whether results provided by several tools
      used to measure urgency in clinical trials could be cross-related to each other
      in a meaningful way. METHODS: The wording of various tools used to measure
      urgency in OAB was compared against the definition of urgency proposed by the
      International Continence Society (ICS). Urgency data were evaluated from two
      randomised, double-blinded, placebo-controlled trials with solifenacin in which
      seven tools were used to measure urgency as a primary or secondary outcome. In
      particular, subanalyses were available from these tools, which measured urgency
      equating to the ICS definition, excluding data points that could be interpreted
      as normal/strong desire to void. RESULTS: Baseline scores for ICS-defined urgency
      differed between the tools, which might reflect imprecision in their wording and
      consequent overlap between urgency and normal/strong desire to void. All the
      tools detected broadly similar mean percentage reductions in the number of
      urgency episodes from baseline to the endpoint of the studies. CONCLUSIONS:
      Urgency should be the primary or co-primary endpoint for future studies of OAB
      and detrusor overactivity. Greater clarity is needed in the development of
      instruments for measuring urgency, so that they do not confuse urgency with
      normal bladder sensations; more education and guidance are needed on how urgency
      is defined.

PMID- 21853324
TI  - Are intra-tympanically administered steroids effective in patients with sudden
      deafness? Implications for current clinical practice.
AB  - Over 60 years since its first report, sudden sensorineural hearing loss (SSNHL)
      still represents an ill-explained condition, with potentially devastating effects
      for the quality of life of previously well patients. The present study critically
      reviewed the available evidence regarding the efficacy of intra-tympanic steroid
      administration in the treatment of SSNHL. Factors affecting that efficacy were
      also explored. The literature was systematically reviewed in Medline and other
      database sources until July 2011, and analyzed through critical analysis of
      pooled data. The study selection included multi-center prospective randomized
      control trials, prospective randomized comparative, prospective comparative and
      prospective studies, retrospective comparative and retrospective studies. The
      total number of analyzed studies was 43. Intra-tympanic steroids appear to be
      effective as primary (strength of recommendation A), or salvage treatment
      (strength of recommendation B) in SSNHL. It is difficult to draw definite
      conclusions regarding the efficacy of combination therapy. The identification of
      a time window for effective treatment in the former two approaches yields a grade
      C strength of recommendation. Primary intra-tympanic treatment is the most
      effective modality in terms of complete hearing recovery (34.4% cure rate). There
      is not enough evidence to attribute treatment failures to impaired permeability
      of the round window membrane. Most complications of intra-tympanic treatment are
      minor, temporary, and conservatively managed. Intra-tympanic steroids can
      theoretically provide a more organ-specific treatment in patients with SSNHL. The
      observation that they seem effective both as primary and salvage treatment
      modalities with a very low complication rate may have serious implications for
      current clinical practice.

PMID- 21853325
TI  - An siRNA screen identifies transmembrane 7 superfamily member 3 (TM7SF3), a seven
      transmembrane orphan receptor, as an inhibitor of cytokine-induced death of
      pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Pro-inflammatory cytokines induce death of pancreatic beta
      cells, leading to the development of type 1 diabetes. We sought to identify novel
      players and the underlying mechanisms involved in this process. METHODS: A high
      throughput screen of 3,850 mouse small interfering RNAs (siRNAs) was performed in
      cytokine-treated MIN6 beta cells. Cells were transfected with the different
      siRNAs and then treated with a combination of TNFalpha, IL-1beta and IFNgamma.
      Cellular apoptosis (caspase-3/7 activity), and changes in cellular reducing power
      and cell morphology were monitored. The resulting data were analysed and the
      corresponding z scores calculated. RESULTS: Several gene families were identified
      as promoting cytokine-induced beta cell apoptosis, the most prominent being those
      encoding ubiquitin ligases and serine/threonine kinases. Conversely,
      deubiquitinating enzymes appeared to reduce apoptosis, while protein phosphatases
      were mainly associated with lowering cellular reducing power. The screen
      suggested with high confidence the involvement of several novel genes in cytokine
      induced beta cell death, including Camkk2, Epn3, Foxp3 and Tm7sf3, which encodes
      an orphan seven transmembrane receptor. siRNAs to Tm7sf3 promoted cytokine
      induced death of MIN6 cells and human pancreatic islets, and abrogated insulin
      secretion in these cells. These findings implicate transmembrane 7 superfamily
      member 3 as a potential new player in the inhibition of cytokine-induced death
      and in the promotion of insulin secretion from pancreatic beta cells.
      CONCLUSIONS/INTERPRETATION: The signalling pathways and novel genes that we
      identified in this screen and that mediate beta cell death offer new possible
      targets for therapeutic intervention in diabetes and its adverse complications.

PMID- 21853326
TI  - Microbial processes in the Athabasca Oil Sands and their potential applications
      in microbial enhanced oil recovery.
AB  - The Athabasca Oil Sands are located within the Western Canadian Sedimentary
      Basin, which covers over 140,200 km(2) of land in Alberta, Canada. The oil sands
      provide a unique environment for bacteria as a result of the stressors of low
      water availability and high hydrocarbon concentrations. Understanding the
      mechanisms bacteria use to tolerate these stresses may aid in our understanding
      of how hydrocarbon degradation has occurred over geological time, and how these
      processes and related tolerance mechanisms may be used in biotechnology
      applications such as microbial enhanced oil recovery (MEOR). The majority of
      research has focused on microbiology processes in oil reservoirs and oilfields;
      as such there is a paucity of information specific to oil sands. By studying
      microbial processes in oil sands there is the potential to use microbes in MEOR
      applications. This article reviews the microbiology of the Athabasca Oil Sands
      and the mechanisms bacteria use to tolerate low water and high hydrocarbon
      availability in oil reservoirs and oilfields, and potential applications in MEOR.

PMID- 21853327
TI  - Potential for industrial products from the halophilic Archaea.
AB  - The halophilic Archaea are a group of microorganisms that have not been
      extensively considered for biotechnological applications. This review describes
      some of the enzymes and products and the potential applications of this unique
      group of microorganisms to various industrial processes. Specifically, the
      characteristics of the glycosyl hydrolases, lipases and esterases, proteases,
      biopolymers and surfactants, as well as some miscellaneous other activities will
      be described.

PMID- 21853328
TI  - Tomato chlorotic leaf distortion virus, a new bipartite begomovirus infecting
      Solanum lycopersicum and Capsicum chinense in Venezuela.
AB  - Virus isolate T217L was obtained from a diseased tomato (Solanum lycopersicum)
      plant showing leaf deformation and chlorotic mottle symptoms near Maracaibo in
      the state of Zulia, Venezuela. Full-length DNA-A and DNA-B molecules of T217L
      were cloned and sequenced. The genome organization of T217L was identical to the
      bipartite genomes of other begomoviruses described from the Americas.
      Characteristic disease symptoms were reproduced in S. lycopersicum and Capsicum
      annum plants inoculated using the cloned viral DNA-A and DNA-B components,
      confirming disease aetiology. A sequence analysis of DNA-A showed that the T217L
      isolate has the highest sequence identity (84%) with sida yellow mosaic Yucatan
      virus (SiYMYuV), sida golden mosaic Honduras virus (SiGMHV) and bean dwarf mosaic
      virus (BDMV) isolates. This is less than the 89% identity in the DNA-A component
      that has been defined as the threshold value for the demarcation of species in
      the genus Begomovirus. The molecular data show that isolate T217L belongs to a
      novel tentative begomovirus species, for which the name tomato chlorotic leaf
      distortion virus is proposed. TCLDV was also detected in symptomatic C. chinense
      plants growing near the T217L-infected plant.

PMID- 21853329
TI  - Development of a sensitive method for selection of affinity ligand for trypsin
      using quartz crystal microbalance sensor.
AB  - In this work, a new methodology is developed for selection of affinity ligands
      towards the enzyme "trypsin" using quartz crystals microbalance (QCM) technique.
      To achieve this goal, the surface amination of gold plated QCM crystals was
      achieved in 13.56 MHz plasma polymerization system by using ethylenediamine.
      Three different ligands (i.e., 4-aminobenzamidine, 4-aminobenzoic acid, and
      phenylalanine) were immobilized on the aminated QCM crystals surface via
      glutaraldehyde coupling. All three ligand immobilized QCM crystals were
      characterized and compared under different experimental conditions. It was
      observed that the benzamidine ligand showed higher affinity to trypsin with a
      dissociation constant on the order of 1.76 * 10(-9) M, which is within the range
      of 10(-4)-10(-8) M for affinity ligands. Thus, its selectivity was suitable for
      purification of trypsin from biological fluids.

PMID- 21853330
TI  - Kinetic models of ribonucleic acid fermentation and continuous culture by Candida
      tropicalis no.121.
AB  - During ribonucleic acid fermentation, the fermentative processes were researched
      at pH controlled at 4.0 and under natural conditions. Unstructured models in a 50
      L airlift fermentor were established for batch RNA production at pH 4.0 using the
      Verhulst equation for microbial growth, the Luedeking-Piret equation for product
      formation and a Luedeking-Piret-like equation for substrate uptake. Parameters of
      the kinetic models were determined using origin 7.5. Based on the models
      estimated above, another batch fermentation experiment was conducted in a 300-L
      airlift fermentor, which demonstrated that the models could be useful for RNA
      production on an industrial scale. Additionally, continuous fermentation based on
      kinetic models was proposed to make full use of substrates and reduce the cost of
      waste water treatment. As a result, although the DCW and RNA concentration were
      11.5 and 1.68 g L(-1), which were lower than that of batch fermentation, the
      sugar utilization increased by 14.3%, while the waste water decreased by more
      than 90%.

PMID- 21853331
TI  - Characterization of an H4N2 avian influenza virus isolated from domestic duck in
      Dongting Lake wetland in 2009.
AB  - In January 2009, an H4N2 subtype of avian influenza virus [A/duck/Hunan/8-19/2009
      (H4N2)] was isolated from domestic ducks in Dongting Lake wetland. The whole
      genome of the virus was sequenced and the results indicated that multiple gene
      segments of the virus had a high homology with viruses isolated from wild
      waterfowl, which indicated that the virus was probably transmitted from wild
      waterfowl to domestic ducks. Phylogenetic analysis revealed that the each gene
      belonged to the Eurasian lineage of avian influenza viruses, but genetic
      reassortment occurs between viruses of different subtypes.

PMID- 21853332
TI  - Resistance to multiple viruses in transgenic tobacco expressing fused, tandem
      repeat, virus-derived double-stranded RNAs.
AB  - Transgenic tobacco plants expressing fused, tandem, inverted-repeat, double
      stranded RNAs derived either from the three viruses [potato virus Y (PVY), potato
      virus A (PVA), and potato leafroll virus (PLRV)] or the five viruses [PVY, PVA,
      PLRV as well as tobacco rattle virus (TRV), and potato mop-top virus (PMTV)] were
      generated in this study to examine whether resistance could be achieved against
      these three viruses or five viruses, respectively, in the same plant. The
      transgenic lines were engineered to produce 600- or 1000-bp inverted hairpin
      transcripts with an intron, in two orientations each, which were processed to
      silencing-inducing RNAs (siRNAs). Fewer lines were regenerated from the
      transformants with either 1000-bp inverted hairpin transcripts, or a sense-intron
      antisense orientation versus antisense-intron-sense orientation. Resistances to
      PVA and two strains of PVY (-O and -N) were achieved in plants from most of lines
      examined, as well as resistance to co-infection by a mixture of PVY-O and PVA,
      applied to the plants by either rub inoculation or using aphids. This was
      regardless of the orientation of the inserted sequences for the 600-bp insert
      lines, but only for one orientation of the 1000-bp insert lines. The lines
      containing the 1000-bp inserts also showed resistance to infection by TRV
      inoculated by rub inoculation and PMTV inoculated by grafting. However, all the
      lines showed only low-to-moderate (15-43%) resistance to infection by PLRV
      transmitted by aphids. The resistances to the various viruses correlated with the
      levels of accumulation of siRNAs, indicating that the multiple resistances were
      achieved by RNA silencing.

PMID- 21853333
TI  - Role of GIS in social sector planning: can developing countries benefit from the
      examples of primary health care (PHC) planning in Britain?
AB  - Social sector planning requires rational approaches where community needs are
      identified by referring to relative deprivation among localities and resources
      are allocated to address inequalities. Geographical information system (GIS) has
      been widely argued and used as a base for rational planning for equal resource
      allocation in social sectors around the globe. Devolution of primary health care
      is global strategy that needs pains taking efforts to implement it. GIS is one of
      the most important tools used around the world in decentralization process of
      primary health care. This paper examines the scope of GIS in social sector
      planning by concentration on primary health care delivery system in Pakistan. The
      work is based on example of the UK's decentralization process and further
      evidence from US. This paper argues that to achieve benefits of well informed
      decision making to meet the communities' needs GIS is an essential tool to
      support social sector planning and can be used without any difficulty in any
      environment. There is increasing trend in the use of Health Management
      Information System (HMIS) in Pakistan with ample internet connectivity which
      provides well established infrastructure in Pakistan to implement GIS for health
      care, however there is need for change in attitude towards empowering localities
      especially with reference to decentralization of decision making. This paper
      provides GIS as a tool for primary health care planning in Pakistan as a starting
      point in defining localities and preparing locality profiles for need
      identification that could help developing countries in implementing the change.

PMID- 21853334
TI  - Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during
      prolonged cultivation.
AB  - The degradation of environmental conditions, such as nutrient depletion and
      accumulation of toxic waste products over time, often lead to premature apoptotic
      cell death in mammalian cell cultures and suboptimal protein yield. Although
      apoptosis has been extensively researched, the changes in the whole cell proteome
      during prolonged cultivation, where apoptosis is a major mode of cell death, have
      not been examined. To our knowledge, the work presented here is the first whole
      cell proteome analysis of non-induced apoptosis in mammalian cells. Flow
      cytometry analyses of various activated caspases demonstrated the onset of
      apoptosis in Chinese hamster ovary cells during prolonged cultivation was
      primarily through the intrinsic pathway. Differential in gel electrophoresis
      proteomic study comparing protein samples collected during cultivation resulted
      in the identification of 40 differentially expressed proteins, including four
      cytoskeletal proteins, ten chaperone and folding proteins, seven metabolic
      enzymes and seven other proteins of varied functions. The induction of seven ER
      chaperones and foldases is a solid indication of the onset of the unfolded
      protein response, which is triggered by cellular and ER stresses, many of which
      occur during prolonged batch cultures. In addition, the upregulation of six
      glycolytic enzymes and another metabolic protein emphasizes that a change in the
      energy metabolism likely occurred as culture conditions degraded and apoptosis
      advanced. By identifying the intracellular changes during cultivation, this study
      provides a foundation for optimizing cell line-specific cultivation processes,
      prolonging longevity and maximizing protein production.

PMID- 21853335
TI  - Preventive effects of protopanaxadiol and protopanaxatriol ginsenosides on liver
      inflammation and apoptosis in hyperlipidemic apoE KO mice.
AB  - Ginsenosides, bioactive compounds of Panax Ginseng C.A. Meyer, are divided into
      protopanaxadiol (PD) and protopanaxtriol (PT). The aim of this study was to
      evaluate the protective effects of different PD and PT combination ratios on
      liver inflammation and apoptosis in hyperlipidemic apo E KO mice. R1 (PD/PT = 1,
      high Rg(1) and Rb(1)) and R2 (PD/PT = 2, high Re and Rd) extracts were
      intraperitoneally injected by 100 mg/kg/day at the 8th week. R1 and R2 improved
      atherogenic indices by increasing HDL and lowering total cholesterol (TC) and
      triacylglyceride (TG) selectively. R1 decreased lipid peroxides (LPO) level in
      plasma and liver tissue of hyperlipidemic mice, and R2 lowered plasma
      malondialdehyde(MDA) level. R1 and R2 not only regulated the expression of
      cyclooxygenase (COX)-2, IkappaB-alpha, phopho-ERK 1/2, and phopho-SAPK/JNK levels
      but also were significantly effective in blocking apoptotic signals, such as
      caspase-8, -9, as well as the cleavage of PARP in liver. Different combinational
      treatment of PD and PT extracts might ameliorate the liver inflammation and
      apoptosis in hyperlipidemic apo E KO mice, which is atherosclerotic animal model.

PMID- 21853336
TI  - Expression and purification of peanut oleosins in insect cells.
AB  - Oleosins contain a unique hydrophobic domain which is inserted into the oil
      matrix and are involved in the formation and stability of plant oil bodies. These
      proteins have also been reported to possess some allergenic properties.
      Therefore, knowledge of its three-dimensional structure is vital for further
      structural and immunological characterization. However, due to the difficulty of
      soluble recombinant expression in Escherichia coli, no studies have been done in
      line with this goal. Here, we have developed a novel expression and purification
      system for three peanut oleosin isoforms (14 k, 16 k, and 18 kDa oleosins).
      Oleosin cDNAs were cloned and subsequently expressed in soluble form in insect
      cell-baculovirus system. Recombinant proteins can be purified to homogeneity
      using only Ni Sepharose affinity chromatography. Thermal denaturation midpoint
      temperatures of recombinant oleosins were also assayed and found to be very
      similar to that of native oleosins, indicating proper structural conformation of
      the recombinant proteins.

PMID- 21853337
TI  - Improved Agrobacterium-mediated transformation of cowpea via sonication and
      vacuum infiltration.
AB  - An improved method of Agrobacterium-mediated transformation of cowpea was
      developed employing both sonication and vacuum infiltration treatments. 4 day-old
      cotyledonary nodes were used as explants for co-cultivation with Agrobacterium
      tumefaciens strain EHA105 harbouring the binary vector pSouv-cry1Ac. Among the
      different injury treatments, vacuum infiltration and their combination treatments
      tested, sonication for 20 s followed by vacuum infiltration for 5 min with A.
      tumefaciens resulted in highest transient GUS expression efficiency (93% explants
      expressing GUS at regenerating sites). After 3 days of co-cultivation, the
      explants were cultured in 150 mg/l kanamycin-containing selection medium and
      putative transformed plants were recovered. The presence, integration and
      expression of nptII and cry1Ac genes in T0 transgenic plants were confirmed by
      polymerase chain reaction (PCR), genomic Southern and qualitative reverse
      transcription (RT)-PCR analysis. Western blot hybridization and enzyme-linked
      immunosorbent assay (ELISA) detected and demonstrated the accumulation of Cry1Ac
      protein in transgenic plants. The cry1Ac gene transmitted in a Mendelian fashion.
      The stable transformation efficiency increased by 88.4% using both sonication
      assisted Agrobacterium-mediated transformation (SAAT) and vacuum infiltration
      than simple Agrobacterium-mediated transformation in cowpea.

PMID- 21853338
TI  - Efficacy of chitin-PAA-GTMAC gel in promoting wound healing: animal study.
AB  - Acrylic grafted chitin (chitin-PAA) was modified with glycidyltrimethylammonium
      chloride (GTMAC) with the aim of promoting wound healing. The chitin-PAA-GTMAC
      gels with different GTMAC contents were compared with the original chitin-PAA gel
      and Intrasite gel for their efficacy in deep wound healing of Wistar rats. Four
      full-thickness wounds were made on the dorsal skin of rats and then each was
      treated with 4 materials; chitin-PAA, chitin-PAA-GTMAC(1:4), chitin-PAA
      GTMAC(1:10) and Intrasite gel. During 18 days of treatment, the wounds were
      visually observed and calculated for wound size using image analysis program.
      Skin wound tissues of sacrificed rats were processed for routine histological
      observation and immunohistochemistry of proliferating cell nuclear antigen
      (PCNA). The wounds covered with the chitin derivatives either with or without
      GTMAC showed a significant reduction in wound size in day 9 in comparison with
      day 12 for those covered with Intrasite gel. The faster rate and the better
      pattern of epidermal development observed in histological study as well as the
      higher dermal cell proliferation (PCNA expression) also demonstrated the better
      efficiency in wound healing of the chitin derivatives than Intrasite. The
      earliest epidermal development of the wounds treated with chitin-PAA-GTMAC (1:4)
      among the tested materials suggested the most promising of this material for the
      treatment of full-thickness open wound.

PMID- 21853339
TI  - Body weight and health-related quality of life in Catalonia, Spain.
AB  - Obesity poses important burdens not only on the individuals whose quality of life
      is reduced but on national welfare systems that have to face growing premature
      mortality rates, increase healthcare expenditures to treat obesity-related
      diseases, and earmark vast amounts of healthcare resources for prevention. The
      main goal of this paper is to analyze the relationship between excess body weight
      and different dimensions of health-related quality of life for people 16 years
      and older and to identify the health dimensions most affected by excess weight.
      We have drawn data from the Catalonia Health Survey (2006). Our results reveal a
      relationship between excess weight and health-related quality of life. Even after
      controlling for socio-economic status and objective health variables, excess
      weight is shown to have a significant negative effect on health-related quality
      of life. Subjects responses revealed that the negative effect of excess weight
      was felt the strongest in the health-related quality of life dimensions of
      mobility and pain/discomfort. Our results indicate there are important
      differences among gender and age groups. Women and older people are more likely
      to suffer from the negative consequences of excess weight.

PMID- 21853340
TI  - A cost-effectiveness analysis of the Incredible Years parenting programme in
      reducing childhood health inequalities.
AB  - Early onset of behavioural problems has lasting negative effects on a broad range
      of lifetime outcomes, placing large costs on individuals, families and society. A
      number of researchers and policy makers have argued that early interventions
      aimed at supporting the family is the most effective way of tackling child
      behaviour problems. This study forms the economic component of a randomised
      evaluation of the Incredible Years programme, a programme aimed at improving the
      skills and parenting strategies of parents of children with conduct problems. Our
      results show that the programme provides a cost-effective way of reducing
      behavioural problems. Furthermore, our cost analysis, when combined with a
      consideration of the potential long-run benefits, suggests that investment in
      such programmes may generate favourable long-run economic returns.

PMID- 21853341
TI  - Expression and localization of four uroplakins in urothelial preneoplastic
      lesions.
AB  - In superficial umbrella cells of normal urothelium, uroplakins (UPs) are
      assembled into urothelial plaques, which form fusiform vesicles (FVs) and
      microridges of the apical cell surface. Altered urothelial differentiation causes
      changes in the cell surface structure. Here, we investigated ultrastructural
      localization of UPIa, UPIb, UPII and UPIIIa in normal and cyclophosphamide
      induced preneoplastic mouse urothelium. In normal urothelium, terminally
      differentiated umbrella cells expressed all four UPs, which were localized to the
      large urothelial plaques covering mature FVs and the apical plasma membrane. The
      preneoplastic urothelium contained two types of superficial cells with altered
      differentiation: (1) poorly differentiated cells with microvilli and small, round
      vesicles that were uroplakin-negative; no urothelial plaques were observed in
      these cells; (2) partially differentiated cells with ropy ridges contained
      uroplakin-positive immature fusiform vesicles and the apical plasma membrane.
      Freeze-fracturing showed small urothelial plaques in these cells. We concluded
      that in normal urothelium, all four UPs colocalize in urothelial plaques.
      However, in preneoplastic urothelium, the growth of the uroplakin plaques was
      hindered in the partially differentiated cells, leading to the formation of
      immature FVs and ropy ridges instead of mature FVs and microridges. Our study
      demonstrates that despite a lower level of expression, UPIa, UPIb, UPII and
      UPIIIa maintain their plaque association in urothelial preneoplastic lesions.

PMID- 21853342
TI  - Clinical value of Tiam1-Rac1 signaling in primary gallbladder carcinoma.
AB  - Tiam1-Rac1 signaling plays an important role in the migration, invasion and
      metastasis of tumor cells. The aim of the present study was to clarify the
      clinical value of Tiam1 and Rac1 expression in primary gallbladder carcinoma
      (PGC). Eighty-six PGC tissues were evaluated by immunohistochemistry for Tiam1
      and Rac1 expression. The association of Tiam1 and Rac1 expression with
      clinicopathological characteristics and the univariate survival analysis for the
      influence of Tiam1 and Rac1 expression on the overall survival were analyzed.
      Tiam1 and Rac1 immunoreactivities were observed in 72 (83.7%) and 68 (79.1%) of
      the 86 PGC cases, but not in the non-neoplastic gallbladder tissues,
      respectively. The tumors with the positive expression of Tiam1 and Rac1 more
      frequently showed lymph node metastasis (P = 0.01 and 0.008), lymphovascular
      invasion (P = 0.009 and 0.01) and recurrence (both P = 0.01), respectively. In
      addition, the tumors with the positive expression of Tiam1 and Rac1 significantly
      tended to show deeper invasion depth (P = 0.007 and 0.005) and higher TNM stage
      (both P = 0.005). The Kaplan-Meier survival curves demonstrated that patients
      with the positive expression of Tiam1 and Rac1 had a significantly shorter
      survival time than those patients with their negative expression (both P = 0.01).
      Multivariate analysis revealed that the positive expression of Tiam1 (P = 0.02)
      and Rac1 (P = 0.02), as well as TNM stage (P = 0.04), to be independently
      associated with a poor prognosis of patients with PGC. The data from this study
      suggest for the first time that Tiam1 and Rac1 are frequently expressed in PGC
      and are associated with decreased survival of the patients. Therefore, Tiam1 and
      Rac1 expressions may be independent predictors for the poor prognosis in patients
      with PGC.

PMID- 21853343
TI  - Clinical relevance of a new pre-treatment laboratory prognostic index in patients
      with oral squamous cell carcinoma.
AB  - The purpose of this retrospective study was to develop a pre-treatment laboratory
      prognostic index (LPI) based on laboratory results that might serve as an
      extension to clinicopathological parameters for prognosis and treatment in
      patients with oral squamous cell carcinoma (OSCC). Pre-treatment LPI was
      calculated from C-reactive protein (CRP), hemoglobin (Hb) levels, and count of
      white blood cells (WBCs) due to significant (P < 0.05) association with
      locoregional recurrence measured for each parameter by receiver operating
      characteristic (ROC) curves in 187 patients with OSCC. Positive predictive values
      (+PV, precision rate) and negative predictive values (-PV) of LPI were measured.
      Likelihood ratios (LRs) were used to assess how good the pre-treatment LPI
      diagnostic test is to determine locoregional recurrence of the disease. CRP
      expression by cancer cells was confirmed by immunocytochemistry and FACS
      analysis. ROC analysis determined cutoff values for CRP levels, Hb levels, and
      WBC count and showed significant differences between nonrecurrent and recurrent
      group of OSCC. On univariate analysis, patients with high pre-treatment LPI (LPI
      >= 2, hazard ratio (HR) = 3.8670, 95% confidence interval (CI) = 2.2518-6.6407, P
      < 0.0001) had a significant poorer prognosis. Multivariate analysis showed that
      the most important independent prognostic factor was high pre-treatment LPI (LPI
      >= 2, HR = 3.6450, 95% CI = 2.3964-5.5441, P < 0.0001). Moreover, pre-treatment
      LPI >= 2 showed high probability that locoregional recurrence will be present
      later (+PV, LPI >= 2, 86.4%, 95% CI = 65.1-97.1). High +LR gave an excellent
      indication for a good quality of the test (LR+, LPI >= 2, 12.77, 95% CI = 8.8
      18.6). Immunohistochemistry and FACS analysis confirmed inflammatory CRP
      expression by cancer cells. This study highlights the combination of inflammatory
      CRP levels, Hb levels, and WBC count as the most important independent prognostic
      factor in predicting disease recurrence of patients with OSCC. LPI can be used as
      a pre-treatment inflammatory biomarker that may identify OSCC with a more
      aggressive biological phenotype of the disease and might be helpful for guiding
      further post-operative treatment in OSCC.

PMID- 21853344
TI  - Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only
      metastases of treatment naive small-cell lung cancer: a phase II study.
AB  - To study the treatment outcomes of brain-only metastases from small-cell lung
      cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain
      and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-naive
      SCLC patients with brain-only metastases in Sun yat-sen University were enrolled.
      Treatment contained initial EP chemotherapy with concurrent whole-brain
      radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3,
      cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy
      in 10 fractions was started within 1 week from the beginning of chemotherapy
      followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy.
      Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was
      given totally 6 cycles for no tumor progression. Thirty-four patients were
      evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief.
      Objective responses in the brain and primary thoracic lesions were observed in 26
      (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The
      median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival
      rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR
      response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and
      43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment
      strategy of concurrent chemotherapy with brain and thoracic RT might achieve
      promising survival outcomes comparable to limited-stage SCLC in initially
      diagnosed SCLC with brain-only metastases.

PMID- 21853345
TI  - Long-term chemotherapy may prolong survival in advanced non-small-cell lung
      cancer among responders to first-line chemotherapy.
AB  - Survival in patients with advanced non-small-cell lung cancer (NSCLC) has
      substantially improved. Long-term chemotherapy with epidermal growth factor
      tyrosine kinase inhibitors (EGFR-TKIs) and other agents has been associated with
      long survival. We retrospectively examined the associations between overall
      survival (OS) and clinical variables in patients with advanced NSCLC who received
      at least one dose or course of outpatient chemotherapy in our institution. Of 360
      patients who received first-line chemotherapy between January 1, 2004 and
      December 31, 2007, 185 subsequently received additional outpatient chemotherapy
      and 175 underwent inpatient chemotherapy only. Of the 185 patients, 147 (79.5%),
      96 (51.9%), and 60 (32.4%) received second-line, third-line, and fourth-line
      chemotherapy, respectively. Patients who received outpatient chemotherapy had
      significantly longer median OS (22.3 months) than did those undergoing inpatient
      chemotherapy only (7.6 months; P < 0.0001). In univariate analysis of the 185
      patients, sex, performance status (PS), smoking status, stage, best response to
      first-line chemotherapy, use of docetaxel, and EGFR-TKIs were significantly
      associated with OS (P values: 0.0019, 0.0066, 0.0001, 0.0231, 0.0011, 0.0250, and
      0.0023, respectively). In multivariate analysis, PS, stage, best response to
      first-line chemotherapy, and use of docetaxel were significantly associated with
      OS (P values: 0.0272, 0.0030, 0.0022, and 0.0376, respectively). Survival was
      significantly longer among patients who responded to docetaxel and/or EGFR-TKIs.
      Long-term chemotherapy did not increase cumulative hospitalization. In patients
      with advanced NSCLC, an effective long-term chemotherapy regimen might prolong
      survival in responders to first-line chemotherapy.

PMID- 21853346
TI  - Highly specific, sensitive and rapid enzyme immunoassays for the measurement of
      acetaminophen in serum.
AB  - Acetaminophen antibodies were purified using affinity chromatography and labelled
      with horseradish peroxidase (HRP). The antibody-HRP conjugate and a new
      acetaminophen derivative were used in the construction of two immunoassay methods
      facilitating the direct quantitative measurement of acetaminophen in serum: a 96
      well microtitre plate and coated-tube ELISAs. A minimum detection limit of 0.2
      MUg mL(-1) and a dynamic range of 0.2 to 1 MUg mL(-1) in serum were achieved
      using the 96-well microtitre plate ELISA. The tube assay was optimised for the
      measurement of the clinically critical acetaminophen concentration of 50 to 250
      MUg mL(-1) of serum. The quantitative and specific tests could be completed
      within less than an hour. Common drugs including aspirin showed less than 0.1%
      cross-reactivity.

PMID- 21853347
TI  - Fucoidan suppresses endocytosis in cultured HeLa cells.
AB  - OBJECTIVE: To evaluate the effects of fucoidan on endocytosis in cultured HeLa
      cells: in vitro using live cell imaging. METHODS: A confocal scanning system and
      an incubation imaging system were used to: observe the effects of fucoidan on the
      initial (6 h) stages of endocytosis using the fl uorescent probe FM1-43 and
      inorganic fl uorescent quantum dot (Q-dots). RESULTS: According to the time-lapse
      images, fucoidan inhibited the: formation of endocytic vesicles in HeLa cells, in
      which the FM1-43 dye was entrapped. Fucoidan also had an inhibitory effect on the
      uptake of the Q-dots by the cell membranes of HeLa cells. CONCLUSION: It was
      concluded: that fucoidan suppresses Ca(2+)-dependent endocytosis in HeLa cells,
      which may be caused by its inhibitory -effects on agonist-induced Ca(2+)
      responses.

PMID- 21853348
TI  - A one-year evaluation of radiographic progression in patients with rheumatoid
      arthritis treated by Qingre Huoxue Decoction ().
AB  - OBJECTIVE: To investigate the effects of Qingre Huoxue Decoction , clearing heat
      and promoting blood flow; QRHXD), on the radiographic progression in patients
      with rheumatoid arthritis (RA) by X-ray imaging. METHODS: Eighty-six patients
      with active RA diagnosed as damp-heat and blood stasis syndrome were randomized
      into a QRHXD group and a QRHXD plus methotrexate (MTX) group, with 43 cases in
      each group. After one-year of treatment, 21 cases in each group (42 in total)
      were evaluated. Radiographs of hands were obtained at the baseline and after 12
      months of treatment. Images were evaluated by investigators blinded to chronology
      and clinical data, and assessed according to the Sharp/Van der Heijde methods.
      RESULTS: High intrareader agreements were reached (mean intraobserver intraclass
      coefficients: 0.95). No significant change in any imaging parameters of joint
      destruction was observed at 12 months in either group; and the differences
      between the two groups were not significant (P>0.05). The mean of the changing
      score in the QRHXD group was 3.5 +/- 4.1, and 2.4 +/- 3.5 in the QRHXD+MTX group,
      while the baseline radiographic score of patients in the QRHXD group was
      relatively higher (18.9 +/- 19.1 vs. 14.0 +/- 14.0). The mean rates of the
      changing scores of the two groups were similar (0.24 +/- 0.28 vs. 0.25 +/- 0.44,
      P=0.40). The severity of progression in the two groups was also similar (P=0.46),
      7 cases without radiographic progression in the QRHXD group and 8 in the
      QRHXD+MTX group, 3 cases with obvious radiographic progression in the QRHXD group
      and 1 in the QRHXD+MTX group. CONCLUSION: Radiographic progression of RA patients
      in both groups is similar, indicating that the QRHXD Decoction has a potential
      role in preventing bone destruction.

PMID- 21853349
TI  - History of Chinese medicinal wine.
AB  - Chinese medicinal wine is one type of a favorable food-drug product invented by
      Chinese ancestors for treating and preventing diseases, promoting people's health
      and corporeity, and enriching people's restorative culture. In the course of
      development of the millenary-old Chinese civilization, Chinese medicinal wine has
      made incessant progress and evolution. In different historical periods, Chinese
      medicinal wine presented different characteristics in basic wine medical
      applications, prescriptions, etc. There are many medical and Materia Medica
      monographs which have systemically and specifically reported on Chinese medicinal
      wine in past Chinese dynasties. By studying leading medical documents, this
      article made an outline review on the invention, development, and characteristics
      of Chinese medicinal wine.

PMID- 21853350
TI  - [Treatment manual for psychotherapy of acute and posttraumatic stress disorders
      after multiple ICD shocks].
AB  - In view of the inceasing number of implanted defibrillators in all industrial
      nations, the number of people who have suffered so-called multiple shocks
      (electrical storm, ES) also increases. Common complaints are severe and
      continuously recurrent massive anxiety, panic attacks, fear of death,
      helplessness and hopelessness, depression, nervosity and irritability as well as
      reclusive and uncontrollable avoidance behaviour, intrusions, nightmares,
      flashbacks, sleeplessness and the inability to show feelings and limitation of
      future perspectives. Because people with an ICD are often physically (very) ill
      and after multiple ICD shocks are additionally very insecure, it would seem
      logical if the inpatient treatment would be carried out in an institution which
      has close connections and is also spatially close to a cardiology department. The
      basis of the diagnostics is the clinical anamnesis and a systematic exploration
      of the trauma situation and the resulting complaints. As an additional diagnostic
      element psychological test procedures should be implemented to determine the core
      symptomatic (anxiety, depression, trauma symptoms). Psychological test procedures
      should be included in the diagnostics so that at the end of treatment it is
      obvious even to the patient which alterations have occurred. The core element of
      inpatient treatment is daily intensive psychotherapy and includes deep
      psychologically well-founded psychotherapy and behavioral therapeutic-oriented
      anxiety therapy as well as cognitive restructuring and elements of eye movement
      desensitization and reprocessing (EMDR). A follow-up examination within 4 months
      of the multiple shocks episode is recommended because symptoms of posttraumatic
      stress disorder often occur after a long latent time period.

PMID- 21853351
TI  - Insights into interstitial flow, shear stress, and mass transport effects on ECM
      heterogeneity in bioreactor-cultivated engineered cartilage hydrogels.
AB  - Interstitial flow in articular cartilage is secondary to compressive and shear
      deformations during joint motion and has been linked with the well-characterized
      heterogeneity in structure and composition of its extracellular matrix. In this
      study, we investigated the effects of introducing gradients of interstitial flow
      on the evolution of compositional heterogeneity in engineered cartilage. Using a
      parallel-plate bioreactor, we observed that Poiseuille flow stimulation of
      chondrocyte-seeded agarose hydrogels led to an increase in glycosaminoglycan and
      type II collagen deposition in the surface region of the hydrogel exposed to
      flow. Experimental measurements of the interstitial flow fields based on the
      fluorescence recovery after photobleaching technique suggested that the observed
      heterogeneity in composition is associated with gradients in interstitial flow in
      a boundary layer at the hydrogel surface. Interestingly, the interstitial flow
      velocity profiles were nonlinearly influenced by flow rate, which upon closer
      examination led us to the original observation that the apparent hydrogel
      permeability decreased exponentially with increased interfacial shear stress. We
      also observed that interstitial flow enhances convective mass transport
      irrespective of molecular size within the boundary layer near the hydrogel
      surface and that the convective contribution to transport diminishes with depth
      in association with interstitial flow gradients. The implications of the
      nonlinearly inverse relationship between the interfacial shear stress and the
      interstitial flux and permeability and its consequences for convective transport
      are important for tissue engineering, since porous scaffolds comprise networks of
      Poiseuille channels (pores) through which interstitial flow must navigate under
      mechanical stimulation or direct perfusion.

PMID- 21853352
TI  - Young age is associated with ipsilateral breast tumor recurrence after breast
      conserving surgery and radiation therapy in patients with HER2-positive/ER
      negative subtype.
AB  - Young breast cancer patients are more likely than old patients to experience
      ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS).
      However, the pathological processes underlying this relationship have not been
      elucidated. We investigated the effect of young age on IBTR in a Korean cohort of
      women with different molecular subtypes of breast cancer. We analyzed data of
      2,102 consecutive breast cancer patients who underwent BCS and post-surgical
      radiation therapy (RT) at two Korean institutions between 2000 and 2005. Patients
      were classified as young (<= 40 years; N = 513) or old (> 40 years; N = 1,589).
      Breast cancer subtype was determined by estrogen receptor (ER), progesterone
      receptor (PR), and HER2. Median follow-up duration was 61 months. The 5-year IBTR
      rate was 3.4% in young patients and 1.1% in old patients (P < 0.001). Univariate
      analysis indicated that IBTR rate in young patients with luminal A and HER2
      subtypes was significantly greater than in old patients with these subtypes (P =
      0.015 and P < 0.001, respectively). Multivariate analysis, which used luminal A
      subtype in old patients as reference, indicated that HER2 subtype in young
      patients was associated with increased risk of IBTR (hazard ratio, HR = 12.24;
      95% CI: 2.54-57.96). Among old patients, HER2 subtype was not associated with
      increased IBTR. In conclusion, young women had a higher rate of IBTR after BCS
      and RT than old women. This difference is mainly among women with HER2 subtype.
      Aggressive local control and adjuvant therapy should be considered for young
      women with HER2 subtype breast cancer.

PMID- 21853354
TI  - Family cohesion and romantic and sexual initiation: a three wave longitudinal
      study.
AB  - Although the relation between family relationships and the timing of sexual debut
      has been the focus of many studies, research on mediating factors is scarce. This
      study examines whether low levels of family cohesion result in an earlier onset
      of romantic and sexual experiences, and whether the link between family cohesion
      and an early sexual debut is mediated by early romantic initiation. A
      longitudinal sample of 314 adolescent girls and 222 boys, aged 12-17 at Wave 1,
      completed questionnaires at three measurement points with three year intervals.
      The results showed that sexual debut followed romantic initiation for 77% of the
      participants. For early adolescent females (aged 12-14), high levels of family
      cohesion resulted in a later sexual debut and this association was fully mediated
      by a delay of romantic initiation. Among boys and older girls, timing of romantic
      initiation did not mediate the link between family cohesion and timing of sexual
      initiation. Early adolescent girls who have negative relationships with their
      parents turn to romantic relationships for intimacy and support, which
      subsequently provide the opportunity for an early sexual debut. Low levels of
      family cohesion thus primarily precipitate romantic initiation and sexual
      initiation appears to be secondary to this process among girls in this age group.

PMID- 21853355
TI  - Youth substance use and body composition: does risk in one area predict risk in
      the other?
AB  - Both substance use and obesity are prevalent among youth. As youth age, substance
      use rates increase and over the past three decades, obesity rates among youth
      have tripled. While these two factors have both short- and long-term health
      impacts, little research has explored how substance use and obesity among youth
      may be related. This study explores the bi-directional longitudinal relationships
      between substance use and body composition. Participants (N = 704; 50.7% female)
      were mostly white (86.4%) with a baseline mean age of 14.7 years. Objectively
      measured body composition was used to calculate body mass index z-scores (BMI z
      score) and percent body fat. Cross-lagged structural equation models, accounting
      for clustering at the school level, were run to determine the longitudinal
      association between body composition and self-reported substance use (alcohol,
      cigarette, and marijuana), adjusting for socio-demographic characteristics,
      pubertal status, and weight satisfaction. Baseline alcohol use predicted
      decreased BMI z-score at follow-up and a similar association with percent body
      fat approached significance. Baseline cigarette use predicted increased percent
      body fat. No longitudinal associations were seen between baseline body
      composition and future substance use. Our results suggest that substance use
      contributes to subsequent body composition; however, body composition does not
      contribute to subsequent substance use. Continued research that explores these
      relationships longitudinally is greatly needed.

PMID- 21853356
TI  - Prognostic factors affecting postmastectomy locoregional recurrence in patients
      with early breast cancer: are intrinsic subtypes effective?
AB  - BACKGROUND: Many studies have investigated the association between the molecular
      subtypes of breast cancer and survival. The aim of this study was to identify the
      effects of intrinsic subtypes of breast cancer and the other clinicopathological
      factors on postmastectomy locoregional recurrence (LRR) in patients with early
      breast cancer. METHODS: The records of 1,195 consecutive early breast cancer
      patients treated with modified radical mastectomy between 2004 and 2008 were
      retrospectively evaluated. The effects of intrinsic subtypes of the tumor
      (luminal A, luminal B, HER2-overexpressing, and triple-negative) and classical
      clinicopathological factors on LRR were identified by univariate and multivariate
      statistical analyses. RESULTS: The median follow-up time was 44 months, and 16
      (1.3%) patients experienced a LRR during this period. In univariate analysis, the
      intrinsic subtypes of breast cancer had a significant effect on LRR (p = 0.002).
      In multivariate analysis, only extranodal invasion and estrogen receptor (ER)
      status were significant predictors of LRR (p = 0.003 and 0.0001, respectively),
      whereas intrinsic subtypes did not reveal a significant relationship with LRR (p
      = 0.57; hazard ratio, 2.9; 95% confidence interval, 0.2-4.7). CONCLUSIONS: The
      results of this study suggest that the extranodal invasion and negative ER status
      should potentially be considered when evaluating the risk of LRR. The predictive
      power of intrinsic subtypes for LRR is less than that of classical pathological
      indicators. This information may be useful in planning management of LRR in early
      breast cancer patients treated with mastectomy.

PMID- 21853357
TI  - Increasing the size limit of benign thyroid lesions resectable by endoscopic
      thyroidectomy via a unilateral axillo-breast approach without gas insufflation.
AB  - BACKGROUND: Endoscopic thyroidectomy is rarely attempted in patients with large
      goitrous lesions. We examined the feasibility and safety of endoscopic
      thyroidectomy via a unilateral axillo-breast approach without gas insufflation
      for resection of large thyroid tumors (>=4 cm). METHODS: The study included 111
      patients: 82 in group 1 (tumor diameter <4 cm) and 29 in group 2 (>= 4 cm).
      Ninety-one patients underwent hemithyroidectomy and 20 underwent total
      thyroidectomy. Local complications, surgical outcomes, and pathological outcomes
      were compared between groups. RESULTS: Postoperative permanent pathology revealed
      24 follicular adenomas and 87 nodular hyperplasias. The mean tumor size in group
      2 was 51.10 +/- 7.66 mm compared to 25.24 +/- 8.14 mm in group 1. The mean volume
      of the thyroid gland in group 2 was 15.60 +/- 3.45 cm(3) compared to 11.27 +/-
      2.40 cm(3) in group 1 (p = 0.000). Mean operating time did not differ
      significantly between groups (p = 0.520). Postoperatively, minor hematomas were
      encountered in three patients (3.7%) in group 1. Three patients in group 1 (3.7%)
      and two in group 2 (6.9%) developed transient unilateral vocal cord palsy (p =
      0.604). Temporary hypocalcemia was observed in six and one patients in groups 1
      and 2, respectively (p = 1.000). No permanent recurrent laryngeal nerve palsy or
      hypoparathyroidism occurred in either group. CONCLUSION: Our data support the
      safety and feasibility of endoscopic thyroidectomy via a unilateral axillo-breast
      approach without gas insufflation, even for the treatment of benign thyroid
      lesions >=4 cm.

PMID- 21853358
TI  - CEACAM1 cytoplastic expression is closely related to tumor angiogenesis and
      poorer relapse-free survival after curative resection of hepatocellular
      carcinoma.

PMID- 21853359
TI  - Telling "everything" but not "too much": the surgeon's dilemma in consultations
      about breast cancer.
AB  - BACKGROUND: Although clinicians are often criticized for giving inadequate
      information to patients with cancer, current recommendations to "provide full
      information" or "all the information patients want" are impractical. We therefore
      examined how surgeons manage information-giving to patients with breast cancer in
      practice, and how their approach compared with what patients wanted. STUDY
      DESIGN: We interviewed 20 patients consulting after surgery in a specialist
      breast unit, and the eight surgeons whom they consulted. Qualitative analysis
      examined surgeon and patient perspectives on the purposes of information.
      RESULTS: Surgeons and patients both stated the importance of "honesty" and
      "telling everything" but surgeons did not want to tell everything they could and
      patients did not want to hear it. Patients wanted information mainly to maintain
      hope, demonstrate the surgeon's expertise, and sustain a personal clinical
      relationship. Surgeons shaped their information-giving for the same reasons while
      providing necessary information about histology and treatment. CONCLUSIONS:
      Surgeons and patients agreed strikingly about the purposes of information and
      indicated that giving information is a more complex task than current
      recommendations imply. We suggest that expert recommendations should catch up
      with practice rather than the reverse. That is, if recommendations are to reflect
      patients' real rather than assumed needs, and be realistic about how surgeons can
      meet these needs, the recommendations should be informed by knowledge of how
      patients and surgeons already reconcile these needs in clinical practice.

PMID- 21853360
TI  - Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN.
AB  - PURPOSE: To explore whether miR-19 is involved in the regulation of multidrug
      resistance (MDR), one of the main causes of breast cancer mortality, and
      modulates sensitivity of tumor cells to chemotherapeutic agents. METHODS: We
      analyzed miRNA expression levels in three MDR cell lines in comparison with their
      parent cell line, MCF-7, using a miRNA microarray. We investigated whether
      inhibitor of miR-19 sensitized MDR cells to chemotherapeutic agents in vitro and
      in vivo. RESULTS: MiR-19 was overexpressed in all three MDR cell lines compared
      to their parental cell line, MCF-7. Expression levels of miR-19 in MDR cells were
      inversely consistent with those of PTEN. Inhibitor of miR-19a restored
      sensitivity of MDR cells to cytotoxic agents; administration of LNA-antimiR-19a,
      a chemo-modified miR-19a inhibitor, sensitized MDR cells to chemotherapeutic
      agents in vivo. CONCLUSION: Our findings demonstrate, for the first time,
      involvement of miR-19 in multidrug resistance through modulation of PTEN and
      suggest that miR-19 may be a potential target for preventing and reversing MDR in
      tumor cells.

PMID- 21853361
TI  - Behavior of monoclonal antibodies: relation between the second virial coefficient
      (B (2)) at low concentrations and aggregation propensity and viscosity at high
      concentrations.
AB  - PURPOSE: To investigate relationship between second virial coefficient B (2) and
      viscosity and aggregation propensity of highly concentrated monoclonal antibody
      (MAbs) solutions. METHODS: Intermolecular interactions of 3 MAbs solutions with
      varying pH were characterized according to B (2) estimated by analytical
      ultracentrifugation sedimentation equilibrium with initial loading concentrations
      <10 mg/mL. Viscosity measurements and stability assessments of MAb solutions at
      concentrations higher than 100 mg/mL were conducted. RESULTS: B (2) of all MAb
      solutions depended on solution pH and have qualitative correlation with viscosity
      and aggregation propensity. The more negative the B (2) values, the more viscous
      the solution, acquiring increased propensity to aggregate. Solutions with B (2)
      values of ~2 * 10(-5) mL.mol/g(2) acquire similar viscosity and aggregation
      propensity regardless of amino acid sequences; for solutions with negative B (2)
      values, viscosity and aggregation propensity differed depending on sequences.
      Results suggest attractive intermolecular interactions represented by negative B
      (2) values are influenced by surface properties of individual MAbs. CONCLUSIONS:
      B (2) can be used, within certain limitations, as an effective indicator of
      viscosity and aggregation propensity of highly concentrated MAb solutions.

PMID- 21853362
TI  - Medication counselling and dispensing practices at community pharmacies: a
      comparative cross sectional study from Pakistan.
AB  - OBJECTIVES: The study aimed to assess and compare medication counselling and
      dispensing practices at community pharmacies in three major cities of Pakistan.
      METHODS: A total of 1113 patient dispenser interactions were observed from a
      randomly selected sample of 371 pharmacies by using convenient sampling technique
      in the three respective cities namely Islamabad (118), Peshawar (120) and Lahore
      (133). The data collection tool was adapted from WHO structure observation form
      and was modified according to the objectives of the study. MAIN OUTCOME MEASURES:
      The process of prescription handling at community pharmacies in terms of patient
      dispenser interaction, prescription validation and medication counseling was
      assessed. The data was coded, entered and analyzed by using SPSS Version 16.
      RESULTS: A total of 1113 patient dispenser interactions were observed at the
      community pharmacies in the three respective cities namely Islamabad (n = 354),
      Peshawar (n = 360) and Lahore (n = 399). Out of 1113 patient/dispenser
      interactions the providers present at the community pharmacies were; pharmacist
      (degree of B-pharm/pharm D) 1.6% (n = 18), pharmacy assistant (diploma in
      pharmacy) 7% (n = 78), diploma holder (certified course of drug dispensing) 5.6%
      (n = 62) and salesmen (no medicine related education) 85.8% (n = 955).There was
      no significant difference in the practice between pharmacists, pharmacy
      assistants, diploma holders and salesmen. Prescription validation was carried out
      in 18% (n = 206) of the cases, drugs verification in 32% (n = 360) of the cases
      while labelling of drugs was performed in only 6% (n = 76) of the cases.
      Completely counselling about medication was provided in 3.1% (n = 35) of the
      cases while no counselling at all was given in 52.7% (n = 582) of the cases.
      CONCLUSION: The process of medication counselling and dispensing practices at
      community pharmacies in Pakistan is not satisfactory. The patients are largely
      handled by unqualified salesmen. Thus there is a strong need to improve
      medication counselling and dispensing practices at community pharmacies by
      improving the skills of the dispensers through a mix of interventions, and law
      should be implemented to ensure presence of qualified person which in turn will
      result in the provision of better patient oriented services at community
      pharmacies.

PMID- 21853363
TI  - Oxycodone induced delirium and agitation in an elderly patient following total
      right knee arthroplasty.
AB  - CASE: Opioids are commonly prescribed for pain, and are often connected to mental
      status adverse events. Delirium is a side effect associated with narcotic
      analgesics, with a higher incidence in the elderly. This report describes an
      elderly male that received a total knee arthroplasty and received morphine post
      operatively. On post-operative day 2, morphine was discontinued due to mental
      status changes and switched to oxycodone/acetaminophen. Twenty-four hours after
      administering oxycodone, the patient's mental status declined. After the patient
      returned to baseline he was transferred to rehabilitation and re-challenged with
      oxycodone/acetaminophen. The re-challenge was inadvertent due to inadequate
      documentation of the adverse event and lack of understanding by the health care
      team of delirium associated with opioids. A similar rapid decline in mental
      status occurred. CONCLUSION: Clinicians should be cognizant of narcotic
      analgesics inducing mental status changes, even with an alternative. Detailed
      documentation of adverse events should occur to avoid accidental re-challenges.

PMID- 21853364
TI  - [Paraneoplastic rheumatic syndromes. A diagnostic challenge].

PMID- 21853365
TI  - [Intraoperative use of electronic patient records by the surgeon. An evaluation
      of the "MI Report" in ENT surgery].
AB  - MOTIVATION: Surgeons often wish to view patient data during surgical procedures.
      To achieve this, the surgeon normally has to get unsterile to view the record
      himself, or request a nurse to do so. This procedure results in a time delay,
      longer anesthesia and higher treatment costs. MATERIAL AND METHODS: The "MI
      Report" (Karl Storz, Tuttlingen, Germany) was evaluated for its impact in ENT
      surgery in daily routine. The system consists of a sensor for gesture recognition
      and a large 52-in. display positioned centrally in the operating room. Usage of
      the system by the surgeon was recorded in 51 surgical procedures. RESULTS:
      Information was retrieved from the display on average 1.2 times per procedure.
      The system was not used at all in 20% of operations. The operation with the
      highest usage rate was tympanoplasty (1.6 views per operation). In 86% of cases,
      the system was used to confirm the therapy underway or make a decision on how to
      proceed with therapy. When trying to activate the system by making a particular
      hand gesture, the surgeon cancelled activation in 31% of attempts. CONCLUSION: A
      relation between the type of operation and information viewed could be shown. A
      benefit for the patient may be assumed on the basis of the reduced effort
      required to retrieve patient data as well as increased intraoperative
      consultation of patient records. The system provides the surgeon with greater
      flexibility and may reduce operating time.

PMID- 21853366
TI  - Recognizing the payoff for investing in prevention.

PMID- 21853367
TI  - Papers presented at the 2010 [corrected] meeting of the Musculoskeletal Infection
      Society: editorial comment.

PMID- 21853368
TI  - Technologies of democracy: experiments and demonstrations.
AB  - Technologies of democracy are instruments based on material apparatus, social
      practices and expert knowledge that organize the participation of various publics
      in the definition and treatment of public problems. Using three examples related
      to the engagement of publics in nanotechnology in France (a citizen conference, a
      series of public meetings, and an industrial design process), the paper argues
      that Science and Technology Studies provide useful tools and methods for the
      analysis of technologies of democracy. Operations of experiments and public
      demonstrations can be described, as well as controversies about technologies of
      democracy giving rise to counter-experiments and counter-demonstrations. The
      political value of the analysis of public engagement lies in the description of
      processes of stabilization of democratic orders and in the display of potential
      alternative political arrangements.

PMID- 21853369
TI  - Synthesis of monomethoxypolyethyleneglycol-cholesteryl ester and effect of its
      incorporation in liposomes.
AB  - The objective of the present study was to synthesize
      monomethoxypolyethyleneglycol-5000 cholesteryl ester [PEG-CH] as a cost-effective
      substitute for polyethyleneglycol-phosphatidylethanolamine and to evaluate the
      influence of its incorporation in liposomal bilayers for surface modification.
      PEG-CH was synthesized and characterized by infrared (IR), proton nuclear
      magnetic resonance spectroscopy ((1)H NMR), and differential scanning calorimetry
      (DSC) studies. Influence of incorporation of PEG-CH in liposomes was evaluated on
      various parameters such as zeta potential, DSC, and encapsulation efficiency of a
      hydrophilic drug pentoxyfylline. Conventional and PEG-CH containing
      pentoxyfylline liposomes were formulated and their stability was evaluated at 4
      degrees C for 3 months. PEG-CH could be successfully synthesized with good yields
      and the structure was confirmed by IR, DSC, and (1)H NMR. The incorporation of
      PEG-CH in liposomes resulted in reduction of the zeta potential and broadening of
      the DSC endotherm. Furthermore, incorporation of PEG-CH in liposomes decreased
      the encapsulation efficiency of pentoxifylline in liposomes when compared to
      conventional liposomes. Conventional and PEG-CH containing pentoxyfylline
      liposomes did not show any signs of pentoxyfylline degradation when stored at 4
      degrees C for 3 months.

PMID- 21853370
TI  - Integrin alpha(v)beta3 as a PET imaging biomarker for osteoclast number in mouse
      models of negative and positive osteoclast regulation.
AB  - PURPOSE: The goal of this study was to determine the specificity of 64Cu-CB-TE2A
      c(RGDyK) (64Cu-RGD) for osteoclast-related diseases, such as Paget's disease or
      rheumatoid arthritis. PROCEDURES: C57BL/6 mice were treated systemically with
      osteoprotegerin (OPG) for 15 days or RANKL for 11 days to suppress and stimulate
      osteoclastogenesis, respectively. The mice were then imaged by positron emission
      tomography/computed tomography using 64Cu-RGD, followed by determination of serum
      TRAP5b and bone histology. Standard uptake values were determined to quantify
      64Cu-RGD in bones and other tissues. RESULTS: Mice treated with OPG showed
      decreased bone uptake of 64Cu-RGD at 1, 2, and 24 h post-injection of the tracer
      (p < 0.01 for all time points) compared to vehicle controls, which correlated
      with a post-treatment decrease in serum TRAP5b. In contrast, mice treated with
      RANKL showed significantly increased bone uptake at 2 h post-injection of (64Cu
      RGD (p < 0.05) compared to the vehicle control group, corresponding to increased
      serum TRAP5b and OC numbers as determined by bone histology. CONCLUSIONS: These
      data demonstrate that 64Cu-RGD localizes to areas in bone with increased
      osteoclast numbers and support the use of 64Cu-RGD as an imaging biomarker for
      osteoclast number that could be used to monitor osteoclast-related pathologies
      and their treatments.

PMID- 21853371
TI  - Epidemiology and structural basis of racial differences in fragility fractures in
      Chinese and Caucasians.
AB  - Chinese have similar vertebral fracture prevalence but lower incidence of hip and
      distal forearm fractures than in Caucasians. The underlying structural and
      biomechanical basis of racial differences in bone fragility is still largely
      undefined but Chinese assemble their smaller appendicular skeleton with thicker
      cortices and trabeculae compared with Caucasians. Vertebral fracture prevalence
      is similar by race, but the incidence of hip and distal forearm fractures is
      lower in Chinese than in Caucasians. This racial dimorphism cannot be explained
      by differences in areal bone mineral density (aBMD) as aBMD is lower in Chinese
      mainly due to their smaller size. The underlying structural and biomechanical
      basis of racial differences in bone fragility is still largely undefined but
      Chinese assemble their smaller appendicular skeleton with more mineralised bone
      matrix within it; the cortices are thicker and perhaps less porous while
      trabeculae are fewer but thicker and more connected. This configuration produces
      a bone with a lower surface/volume ratio, which in turn reduces the surface
      available for remodelling to occur upon so that the lower surface/volume ratio
      may make the bone less exposed to remodelling and the thicker cortices and
      trabeculae less vulnerable to remodelling when it does occur during advancing
      age. However, prospective studies are needed to define racial differences at the
      age of onset, rate of bone loss from the intracortical, endocortical and
      trabecular components of the endosteal envelope and bone formation upon the
      periosteal envelope; notions of bone 'loss' are derived mainly from cross
      sectional studies. Studies of the site- and surface-specific changes in bone
      modelling and remodelling are needed to better define racial differences in bone
      fragility in old age.

PMID- 21853373
TI  - Autism-specific primary care medical home intervention.
AB  - Forty-six subjects received primary medical care within an autism-specific
      medical home intervention ( www.autismmedicalhome.com ) and 157 controls received
      standard primary medical care. Subjects and controls had autism spectrum disorder
      diagnoses. Thirty-four subjects (74%) and 62 controls (40%) completed pre and
      post surveys. Controlling for pre-survey medical home status, subjects had 250%
      greater odds of receipt of a medical home at the study end compared to controls
      (p = 0.021). Compared to controls, subjects receiving the intervention reported
      significantly more satisfaction (p = 0.0004), greater shared decision making (p =
      0.0005) and fewer unmet needs (p = 0.067). However, subjects reported no change
      in family stress (p = 0.204).

PMID- 21853374
TI  - Receiver-operating characteristic analysis of multifocal VEPs to diagnose and
      quantify glaucomatous functional damage.
AB  - To test whether multifocal visual evoked potential (mfVEP) recording using two
      perpendicularly placed channels, as previously reported, to measure the degree of
      signal-to-noise ratio (SNR) distribution overlap between a signal window and a
      noise window would efficiently detect and quantify glaucomatous damage. Humphrey
      visual field (HVF) and mfVEP were recorded from 56 patients with primary open
      angle glaucoma and mean deviation less than -15 dB and 62 age-matched
      ophthalmologically normal individuals. Areas under the receiver-operating
      characteristic curve (SNR-AUC) were calculated based on the proportion of mfVEP
      responses that exceeded a specific SNR criterion for both windows. Abnormal
      sectors with an SNR deviated from the previously established norm with P<5% and
      1% were counted. Diagnostic accuracy of the SNR-AUC was similar to that of the
      average total deviation (TD) of the HVF. The hemifield agreement to detect a
      defect in mfVEP and HVF was 77.1-87.3%, which was similar to previous reports
      using multiple channels. Correlation coefficients between SNR-AUC and average TD
      (0.74 in the upper hemifield and 0.65 in the lower) were significantly higher
      than those between the sums of abnormal locations on the mfVEP and HVF
      probability plots (0.27 and 0.33, respectively). Two perpendicular channels can
      detect and quantify functional damage due to glaucoma. The SNR-AUC may be used as
      a global index to quantify diffuse glaucomatous functional loss.

PMID- 21853375
TI  - [Clinical neurological diagnosis of sepsis-associated delirium].
AB  - Sepsis is a frequent emergency and an acute disease which is still highly lethal.
      Due to an early involvement of the brain in terms of a sepsis-associated delirium
      the neurologist plays an important role in the early diagnosis of the
      interdisciplinary disease. The following review details the main diagnostic
      aspects of a sepsis-associated delirium.

PMID- 21853376
TI  - [Eating disorders: new findings for diagnosis and treatment].

PMID- 21853377
TI  - Adolescent disruptive behavior and borderline personality disorder symptoms in
      young adult men.
AB  - Very few studies have prospective information, especially regarding males, on the
      prediction of Borderline Personality Disorder (BPD) in adulthood from psychiatric
      disorders in childhood. Certain childhood disorders, however, have notably
      similar features in common with BPD. In particular, the affective dysfunction,
      hostility and interpersonal conflict of Oppositional Defiant Disorder (ODD) and
      the impulsivity of Attention Deficit Hyperactivity Disorder (ADHD) in particular
      may be indicative of an early developmental path towards BPD. The present study
      uses longitudinal data from a clinical sample of 177 boys, initially between the
      ages of 7 and 12, who were followed up annually to age 18, and who were
      reassessed at age 24 (n = 142). The study examines the prediction from repeated
      childhood measures of psychopathology measured annually through adolescence to
      BPD symptoms assessed at age 24, accounting for the effects of covariates
      including substance use, other personality disorders at age 24 and harsh physical
      punishment. The prevalence of BPD in this sample was consistent with other
      population estimates. Attention Deficit Hyperactivity Disorder (ADHD) and ODD
      were the only child psychiatric disorders to predict BPD symptoms, and the
      oppositional behavioral dimension of ODD was particularly predictive of BPD.
      These results indicate possible developmental links between early psychiatric
      disorders and BPD.

PMID- 21853378
TI  - Serial analysis of gene expression in the chicken otocyst.
AB  - The inner ear arises from multipotent placodal precursors that are gradually
      committed to the otic fate and further differentiate into all inner ear cell
      types, with the exception of a few immigrating neural crest-derived cells. The
      otocyst plays a pivotal role during inner ear development: otic progenitor cells
      sub-compartmentalize into non-sensory and prosensory domains, giving rise to
      individual vestibular and auditory organs and their associated ganglia. The genes
      and pathways underlying this progressive subdivision and differentiation process
      are not entirely known. The goal of this study was to identify a comprehensive
      set of genes expressed in the chicken otocyst using the serial analysis of gene
      expression (SAGE) method. Our analysis revealed several hundred transcriptional
      regulators, potential signaling proteins, and receptors. We identified a
      substantial collection of genes that were previously known in the context of
      inner ear development, but we also found many new candidate genes, such as SOX4,
      SOX5, SOX7, SOX8, SOX11, and SOX18, which previously were not known to be
      expressed in the developing inner ear. Despite its limitation of not being all
      inclusive, the generated otocyst SAGE library is a practical bioinformatics tool
      to study otocyst gene expression and to identify candidate genes for
      developmental studies.

PMID- 21853379
TI  - The genes for gibberellin biosynthesis in wheat.
AB  - The gibberellin biosynthesis pathway is well defined in Arabidopsis and features
      seven key enzymes including ent-copalyl diphosphate synthase (CPS), ent-kaurene
      synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA 20
      oxidase, GA 3-oxidase, and GA 2-oxidase. The Arabidopsis genes were used to
      identify their counterparts in wheat and the TaCPS, TaKS, TaKO, and TaKAO genes
      were cloned from Chinese Spring wheat. In order to determine their chromosome
      locations, expression patterns and feedback regulations, three TaCPS genes, three
      TaKS genes, three TaKO genes, and three TaKAO genes were cloned from Chinese
      Spring wheat. They are mainly located on chromosomes 7A, 7B, 7D and 2A, 2B and
      2D. The expression patterns of TaCPS, TaKS, TaKO, and TaKAO genes in wheat
      leaves, young spikes, peduncles, the third and forth internodes were investigated
      using quantitative PCR. The results showed that all the genes were constitutively
      expressed in wheat, but their relative expression levels varied in different
      tissues. They were mainly transcribed in stems, secondly in leaves and spikes,
      and the least in peduncles. Feedback regulation of the TaCPS, TaKS, TaKO, and
      TaKAO genes was not evident. These results indicate that all the genes and their
      homologs may play important roles in the developmental processes of wheat, but
      each of the homologs may function differently in different tissues or during
      different developmental stages.

PMID- 21853380
TI  - 'Is getting well ever an art?': Psychopharmacology and madness in Robert Lowell's
      Day by Day.
AB  - On the publication of Robert Lowell's Life Studies in 1959, some critics were
      shocked by the poet's use of seemingly frank autobiographical material, in
      particular the portrayal of his hospitalizations for bipolar disorder. During the
      late fifties and throughout the sixties, a rich vein, influenced by Lowell,
      developed in American poetry. Also during this time, the nascent science of
      psychopharmacology competed with and complemented the more established somatic
      treatments, such as psychosurgery, shock treatments, and psychoanalytical
      therapies. The development of Thorazine was a remarkable breakthrough allowing
      patients previously thought incurable to leave hospital. In 1955, the release of
      Miltown, the first 'minor' tranquilizer, was heralded with a media fanfare
      promising a new dawn of psychological cure-all. These two events blurred the
      boundary between 'normality' and madness by making treatment in the community
      more widely possible and by medicalizing more commonplace distress. Lowell's
      early depictions of madness situate it as emblematic of the cultural malaise of
      'the tranquilized fifties.' By his final collection, Day by Day (1977), mental
      illness had lost its symbolic power. These late poems explore the power of art as
      a way of representing and remedying suffering in a culture where
      psychopharmacology has normalized madness.

PMID- 21853381
TI  - Changes in Caenorhabditis elegans life span and selective innate immune genes
      during Staphylococcus aureus infection.
AB  - Caenorhabditis elegans has been increasingly used to study the innate immunity
      and for the screening of microbe/host-specific pathogenic factors. Staphylococcus
      aureus-mediated infections with live C. elegans were performed on solid (full
      lawn) and liquid assays. S. aureus required 90 +/- 10 h for the complete killing
      of C. elegans, but the infection was started only after 32 h of exposure with 20%
      inoculum of S. aureus. The short time exposure studies revealed that, in 20% of
      inoculum, continuous exposure to the pathogen was required for the killing of
      nematode. In 100% of inoculum, only 8 h of exposure was sufficient to kill the C.
      elegans. To evaluate kinetically at the innate immune level, the regulation of
      representative candidate antimicrobial genes was investigated. Both semi
      quantitative reverse transcriptase polymerase chain reaction (PCR) and real-time
      PCR analyses indicated the regulation of candidate immune regulatory genes of
      lysozyme (lys-7), cysteine protease (cpr-2), and C-type lectin (clec-60 and clec
      87) family members during the course of S. aureus infections, indicating the
      possible contribution of the above players during the host immune response
      against S. aureus exposures.

PMID- 21853382
TI  - Percutaneous treatment of an infected aneurysmal sac secondary to aortoesophageal
      fistula with a history of stent-graft treatment for thoracic aortic aneurysm.
AB  - A 68-year-old man who was subjected to stent-grafting of a descending thoracic
      aortic aneurysm (TAA) 4 months previously was admitted to our hospital with
      constitutional symptoms, including high fever, sweating, nausea, vomiting, weight
      loss, and backache. An infected aneurysmal sac was suspected based on computed
      tomography (CT) findings, and an aortoesophageal fistula (AEF) was identified
      during esophagoscopy. CT-guided aspiration was performed using a 20-G Chiba
      needle, confirming the presence of infection. For treatment of the infected
      aneurysmal sac, CT-guided percutaneous catheter drainage in a prone position was
      performed under general anesthesia with left endobronchial intubation. Drainage
      catheter insertion was successfully performed using the Seldinger technique,
      which is not a standard treatment of an infected aneurysmal sac. Improvement in
      the patient's clinical condition was observed at follow-ups, and CT showed total
      regression of the collection in the aneurysmal sac.

PMID- 21853383
TI  - Detection of aneuploidy rate for chromosomes X, Y and 8 by fluorescence in-situ
      hybridization in spermatozoa from patients with severe non-obstructive
      oligozoospermia.
AB  - PURPOSE: To evaluate the frequency of sperm nuclei disomy for chromosomes 8, X,
      and Y in patients with severe non-obstructive oligozoospermia and to assess
      possible correlations between sperm nuclei aneuploidy and semen parameters or a
      particular clinical phenotype. MATERIALS AND METHODS: The sperm aneuploidy rate
      for chromosomes X, Y, and 8 were assessed in 16 infertile men with severe non
      obstructive oligozoospermia and 7 healthy men with normal semen parameters. The
      frequency of sperm aneuploidy was compared between several patients groups
      according to their clinical and biological factors. RESULTS: The total rate of
      chromosomally abnormal spermatozoa was significantly higher in patients with
      severe oligozoospermia compared to control group (P < 0.001). A significant
      relationship was found between the age of patients, sperm concentration, and
      morphology and the mean rate of sex chromosomes disomy. In addition to the low
      sperm count (<5 * 10(6)/ml), an elevated FSH level and an exposed to an elevated
      temperature are two major predictive factors leading to the production of higher
      numbers of chromosomally abnormal gametes. CONCLUSION: Patients with severe
      oligozoospermia, who are potential candidates for assisted reproduction
      technology, presented a high level of sex numerical chromosome abnormalities, and
      consequently are at high risk of chromosome abnormalities in their offspring.

PMID- 21853384
TI  - Tanshinone IIA activates calcium-dependent apoptosis signaling pathway in human
      hepatoma cells.
AB  - Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge,
      has potential anti-tumor activity. The aim of this study was to pinpoint the
      molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human
      hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay
      for cell viability, 10-day culture for colony formation, flow cytometry and
      fluorescence microscopy for apoptosis and cell cycle analysis. Changes in
      intracellular [Ca(2+)] and mitochondrial membrane potential (?psi) reflected the
      calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of
      Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human
      amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and
      time-dependent anticancer effects on BEL-7402 cells through apoptosis and
      G(0)/G(1) arrest. Cells treated with Tan IIA increased their intracellular
      calcium, decreased their mitochondrial membrane potential and induced Bad and MT
      1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In
      conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis
      acts via activation of calcium-dependent apoptosis signaling pathways and
      upregulation of MT 1A expression.

PMID- 21853385
TI  - Genetic diversity of Centella asiatica in China analyzed by inter-simple sequence
      repeat (ISSR) markers: combination analysis with chemical diversity.
AB  - Centella asiatica is an important plant species used in traditional Chinese
      medicine. To help the efficient use and conservation of this species, the genetic
      diversity of C. asiatica populations in China was investigated using inter-simple
      sequence repeat (ISSR) markers. Fourteen natural populations comprising 162
      individuals were included to estimate genetic diversity. At the species level,
      genetic diversity was relatively high (P = 66.33%, H = 0.2183, I = 0.3305). At
      the population level, the genetic diversity of JH (Jinhua, Zhejiang Province,
      China) and JJ (Jiujiang, Jiangxi Province, China) populations was relatively high
      (P = 43.88%, 38.78%, H = 0.1610, 0.1301, I = 0.2376, 0.1957, respectively),
      whereas the genetic diversity of GA (Guang'an, Sichuan Province, China) and EM
      (E'mei, Sichuan Province, China) was relatively low (P = 10.2%, 5.1%, H = 0.0383,
      0.0211, I = 0.0570, 0.0309, respectively). On the basis of Nei's G(st) value,
      more genetic differentiation among populations was determined (G(st) = 0.6573).
      In addition, the 14 populations were clustered into four groups in view of
      abundant ISSR data, which further defined the genetic relationship among
      populations. Interestingly, the genetic clustering result was similar to previous
      chemical clustering results based on high-performance liquid chromatography
      (HPLC) data, which would also classify the 14 populations into four groups. Thus,
      we combined the clustering results and compared their difference. The combined
      analysis and genetic diversity data provide a scientific basis for conserving
      populations of relatively high genetic diversity such as JH and JJ populations
      and establishing good agricultural practices (GAP) for C. asiatica.

PMID- 21853386
TI  - Clodronate and hydroxychloroquine in erosive osteoarthritis: a 24-month open
      randomized pilot study.
AB  - We evaluated the efficacy of clodronate for treating active erosive
      osteoarthritis of the hand and to compare it with hydroxychloroquine. Group A
      consisted of 24 patients treated for 24 months with clodronate 300 mg i.v. for 7
      days, followed by clodronate i.m. 100 mg for 14 days every 3 months. Group B
      comprised 14 patients treated with hydroxychloroquine 400 mg daily for 30 days,
      followed by 200 mg daily for the next 11 months. In group A, 21/24 patients
      completed the trial and obtained significant pain reduction (p < 0.001),
      Dreiser's score (p = 0.012), and number of tender joints (p = 0.011). Strength of
      right (p = 0.04) and left (p = 0.016) hands, physician's global assessment (p <=
      0.001), and patient's global assessment (p = 0.021) improved. In group B, 8/14
      patients completed 12 months of the study, which showed the inefficacy of
      hydroxychloroquine and its lack of acceptance by patients (worsening pain and
      patient's global assessment). Therefore, enrolment was stopped. Differences
      between groups showed a pain decreasing trend for group A and a slightly
      increasing one for group B (p = 0.018). Physician and patient global assessments
      showed a strong increase in group A compared with group B (p < 0.001). Clodronate
      is effective in erosive osteoarthritis; hydroxychloroquine seems to be
      ineffective.

PMID- 21853387
TI  - The advent of successful organ transplantation in the Irish HIV positive cohort.
AB  - BACKGROUND: Liver disease is an increasing cause of morbidity and mortality in
      Human immunodeficiency virus (HIV) positive patients. AIM: To describe the first
      cases of organ transplantation in HIV positive patients in Ireland. METHOD: We
      report the Irish patients with HIV who received liver transplantation and
      performed a chart review. RESULT: Two patients received liver transplantation for
      end stage liver disease caused by Hepatitis C, with survival at 2 years of 100%.
      CONCLUSION: Liver transplantation is a feasible treatment for patients with HIV
      and end stage liver disease. The success of transplantation in the HIV positive
      population should encourage the provision of other medical and surgical
      interventions previously not offered to patients with HIV.

PMID- 21853388
TI  - Neonatal 6-hydroxydopamine lesioning enhances quinpirole-induced vertical jumping
      in rats that were quinpirole primed during postnatal ontogeny.
AB  - Quinpirole-induced vertical jumping is a phenomenon first observed in rats
      treated from birth, once a day for 21 days or more, with the dopamine D2 receptor
      agonist quinpirole. This quinpirole-induced behavioral sensitization is known as
      a priming process. To determine whether dopaminergic innervation influenced this
      priming phenomenon, groups of rats were lesioned at 3 days after birth with the
      neurotoxin 6-hydroxydopamine (6-OHDA; 67 MUg in each lateral ventricle;
      desipramine pretreatment, 20 mg/kg ip, 1 h). Rats were additionally treated daily
      from birth with quinpirole HCl (3.0 mg/kg ip, salt form). Controls received
      saline vehicle in place of 6-OHDA and/or quinpirole. When rats were placed in
      individual observation cages (1 h acclimation) starting at 20 days after birth,
      acute quinpirole treatment produced vertical jumping in the quinpirole-primed
      group; and the effect persisted through the twenty-ninth day. In rats
      additionally lesioned with 6-OHDA, vertical jumping was enhanced at 20, 24,
      26/27, and 28/29 day--with there being as much as a 32-fold increase in vertical
      jumping versus the group that was primed with quinpirole, but not lesioned with 6
      OHDA. This finding indicates that an ontogenetic 6-OHDA lesion enhances
      quinpirole-induced vertical jumping in rats and that dopaminergic innervation may
      normally exert a suppressive effect on vertical jumping.

PMID- 21853389
TI  - Probing the role of IFT particle complex A and B in flagellar entry and exit of
      IFT-dynein in Chlamydomonas.
AB  - Mediating the transport of flagellar precursors and removal of turnover products,
      intraflagellar transport (IFT) is required for flagella assembly and maintenance.
      The IFT apparatus is composed of the anterograde IFT motor kinesin II, the
      retrograde IFT motor IFT-dynein, and IFT particles containing two complexes, A
      and B. In order to have a balanced two-way transportation, IFT-dynein has to be
      carried into flagella and transported to the flagellar tip by kinesin II, where
      it is activated to drive the retrograde IFT back to the flagellar base. In this
      study, we investigated the role of complex A and complex B in the flagellar entry
      and exit of IFT-dynein. We showed that regardless of the amount of complex A, IFT
      dynein accumulated proportionally to the amount of complex B in the flagella of
      fla15/ift144 and fla17-1/ift139, two complex A temperature-sensitive mutants.
      Complex A was depleted from both cellular and flagellar compartments in
      fla15/ift144 mutant. However, in fla17-1/ift139 mutant, the flagellar level of
      complex A was at the wild-type level, which was in radical contrast to the
      significantly reduced cellular amount of complex A. These results support that
      complex A is not required for the flagellar entry of IFT-dynein, but might be
      essential for the lagellar exit of IFT-dynein. Additionally, we confirmed the
      essential role of IFT172, a complex B subunit, in the flagellar entry of IFT
      dynein. These results indicate that complexes A and B play complementary but
      distinct roles for IFT-dynein, with complex B carrying IFT-dynein into the
      flagella while complex A mediates the flagellar exit of IFT-dynein.

PMID- 21853390
TI  - The impact of atraumatic fibrin sealant vs. staple mesh fixation in TAPP hernia
      repair on chronic pain and quality of life: results of a randomized controlled
      study.
AB  - BACKGROUND: Mesh reinforcement has become the standard of care in the open and
      laparoscopic repair of inguinal hernia. Chronic pain after inguinal hernia repair
      is often due to nerve injury by penetrating mesh fixation devices such as staples
      (ST), tacks, or sutures. In several studies on hernioplasty, atraumatic mesh
      fixation with fibrin sealant (FS) proved to be efficient in terms of fixation
      strength and elasticity. Unfortunately, most of these studies did not provide a
      standardized follow-up and assessment of the development of chronic pain (CP) and
      the quality of life (QoL). Therefore, a randomized controlled trial comparing CP
      and QoL after FS fixation of mesh with ST in transabdominal preperitoneal
      hernioplasty (TAPP) was performed at our department. The primary end point of our
      study was to assess the patient outcome by using a visual analog scale (VAS) and
      the short form 36 (SF-36). The evaluation of recurrence rates was the secondary
      aim. METHODS: According to the randomization, a macroporous mesh (TiMESH((r)))
      was fixed in group A (44 patients with 54 inguinal hernias) with FS (TISSEEL) or
      in group B (45 patients with 56 inguinal hernias) with ST (EMS((r)) Stapler). The
      observation period was 1 year with regular clinical check ups and assessment of
      VAS and SF-36. RESULTS: Patient characteristics expressed by BMI, ASA scores, and
      Schumpelick hernia classification were similar in both treatment groups. In each
      group there was one recurrence within 8 (FS) and 9 months (ST) postsurgery. The
      mean preoperative pain values scored by VAS were 1.7 (range = 0-7.5) in the FS
      group and 2.2 (range = 0-6) in the ST group. Postoperative mean VAS scores
      measured at 1 year postsurgery were 0.4 (range = 0-3) in the FS group and 0.9
      (range = 0-7.5) in the ST group. One year postsurgery there was no significant
      difference between the two groups with respect to the parameter pain in the SF-36
      and VAS. CONCLUSION: Fibrin sealant fixation leads to a low rate of hernia
      recurrence and avoids tissue trauma. ST provide similar results in the hand of
      the expert but bear inherent risks of complications due to tissue perforation.

PMID- 21853391
TI  - Prospective randomized controlled trial of simulator-based versus traditional in
      surgery laparoscopic camera navigation training.
AB  - BACKGROUND: Surgical residents often use a laparoscopic camera in minimally
      invasive surgery for the first time in the operating room (OR) with no previous
      education or experience. Computer-based simulator training is increasingly used
      in residency programs. However, no randomized controlled study has compared the
      effect of simulator-based versus the traditional OR-based training of camera
      navigation skills. METHODS: This prospective randomized controlled study included
      24 pregraduation medical students without any experience in camera navigation or
      simulators. After a baseline camera navigation test in the OR, participants were
      randomized to six structured simulator-based training sessions in the skills lab
      (SL group) or to the traditional training in the OR navigating the camera during
      six laparoscopic interventions (OR group). After training, the camera test was
      repeated. Videos of all tests (including of 14 experts) were rated by five
      blinded, independent experts according to a structured protocol. RESULTS: The
      groups were well randomized and comparable. Both training groups significantly
      improved their camera navigational skills in regard to time to completion of the
      camera test (SL P = 0.049; OR P = 0.02) and correct organ visualization (P =
      0.04; P = 0.03). Horizon alignment improved without reaching statistical
      significance (P = 0.20; P = 0.09). Although both groups spent an equal amount of
      actual time on camera navigation training (217 vs. 272 min, P = 0.20), the SL
      group spent significantly less overall time in the skill lab than the OR group
      spent in the operating room (302 vs. 1002 min, P < 0.01). CONCLUSION: This is the
      first prospective randomized controlled study indicating that simulator-based
      training of camera navigation can be transferred to the OR using the traditional
      hands-on training as controls. In addition, simulator camera navigation training
      for laparoscopic surgery is as effective but more time efficient than traditional
      teaching.

PMID- 21853392
TI  - Near-infrared (NIR) laparoscopy for intraoperative lymphatic road-mapping and
      sentinel node identification during definitive surgical resection of early-stage
      colorectal neoplasia.
AB  - BACKGROUND: Appropriate lymphatic assessment is a cornerstone of definitive
      surgical resection for colorectal cancer. Near-infrared (NIR) laparoscopy may
      allow real-time intraoperative identification of territorial lymphatic drainage
      and sentinel nodes in patients with early-stage disease prior to radical basin
      resection. METHODS: With IRB approval and individual consent, consecutive
      patients with radiologically localized neoplasia underwent peritumoral submucosal
      injection of indocyanine green (ICG, a fluorophore capable of injection site
      tattooing and efferent lymphatic migration) prior to standard laparoscopic
      oncological resection. Intraoperatively, a prototype NIR laparoscope provided
      both white light and, by switch activation, NIR irradiation with or without
      discrete spectral back-filtration. Fluorescence identification of sentinel nodes
      prior to formal specimen dissection allowed their identification for separate
      histopathological analysis by in situ clipping when found within the specimen or
      selective lymphadenectomy by "berry-picking" when such nodes lay outside of the
      standard resection field. Concordance with nonsentinel nodes was then analysed.
      RESULTS: Eighteen patients (mean age = 66.4 years [range = 47.9-80.1], mean BMI =
      29.1 [range = 20.0-39.9]) were studied. Fourteen had biopsy-proven carcinoma and
      four had endoscopically unresectable dysplasia. Mesocolic sentinel nodes (mean =
      4.1/patient) were rendered obvious by fluorescence either solely within the
      standard resection field (n = 14) or both within and without the planned field (n
      = 4) within minutes of dye injection in every case. Laparoscopic ultrasound (n =
      5) as well as histopathological analysis demonstrated oncologic correlation of
      mesocolic sentinel with corresponding territory nonsentinel nodes, correctly
      confirming the presence of mesocolic disease in 3 patients and the absence of
      such lymphatic spread in the remaining 15 patients. CONCLUSIONS: In this study,
      NIR laparoscopy with ICG mapping allowed ready and rapid confirmation of
      mesocolic lymphatic drainage patterns and sentinel node identification. With
      further validation, this technology and technique promises precise, tailored
      resection surgery by indicating basin pattern and status in advance of radical
      lymphadenectomy.

PMID- 21853393
TI  - Safety of open technique for first-trocar placement in laparoscopic surgery: a
      series of 6,000 cases.
AB  - BACKGROUND: The open technique for the placement of the first trocar in
      laparoscopic surgery has become the preferred method due to the reduced number of
      complications associated with it. In 2002 we reported our technique, which has
      been widely accepted at many centers, including all the units of our hospital. We
      now report on a series of 6,000 cases in which this technique was used. METHOD:
      The method is the same as that reported by us previously (Surg Endosc 16:1366
      1370, [10]) except for the minor modification of using a Mayo towel clip instead
      of the Allis forceps for holding the cicatrix pillar, as the pillar tends not to
      slip out of the former. During closure, Allis forceps is used to lift the divided
      rectus sheath on each side to take the suture bite and ensure complete secure
      closure. A total of 6,000 consecutive cases have been performed using this
      technique in two tertiary care hospitals over the last 11 years. RESULTS: A total
      of 6,000 cases (5,350 females and 650 males) were operated on over an 11-year
      period. There were no visceral or vascular complications. Four hundred seventy
      five patients (7.9%) had had previous abdominal surgery. The supraumbilical route
      was used in 348 patients and lateral entry in 90 patients. Port-site hernias were
      seen in 25 cases (0.4%) and wound infections in 56 cases (0.9%). The average time
      for trocar placement was 2 min (range = 1-12 min) and the average port size was
      15 mm (range = 12-22 mm). The average time for port closure at the end of the
      procedure was 3 min (range = 1-7 min). CONCLUSIONS: The technique of open-trocar
      placement in laparoscopic surgery has now become standardized, with its safety
      having been well established. Our experience has shown that this technique is
      safe, effective, reproducible, easy to learn, can be performed quickly, and has
      excellent results.

PMID- 21853394
TI  - Survival and quality of life after minimally invasive esophagectomy: a single
      surgeon experience.
AB  - BACKGROUND: Reports on quality of life (QOL) after minimally invasive
      esophagectomy (MIE) have been limited. This report compares perioperative
      outcomes, survival, and QOL after MIEs with open transthoracic esophagectomy
      (TTE) and open transhiatal esophagectomy (THE). METHODS: After institutional
      review board approval, retrospective review of a prospectively maintained
      database identified patients who underwent esophageal resection for esophageal
      cancer at Creighton University between August 2003 and August 2010. Patients with
      preoperative stage 4 disease, emergent procedures, laparoscopic transhiatal
      esophagectomies, or esophagojeujunostomies were excluded from the study. The
      study patients were categorized as having undergone open TTE, open THE, or MIE.
      Overall survival (OS) was the interval between diagnosis and death or follow-up
      assessment. Disease-free survival (DFS) was the interval between surgery and
      recurrence, death, or follow-up assessment. For the patients who survived at
      least 1 year after surgery, QOL was assessed using European Organization for
      Research and Treatment of Cancer (EORTC-QLQ, version 3.0) and esophageal module
      (EORTC-QLQ OES 18) questionnaires. RESULTS: The study criteria were satisfied by
      104 patients. Lymph node harvest with MIE (median = 20) was similar to that with
      open TTEs (median = 19) and significantly higher (P < 0.001) than that with open
      THEs (median = 12). The percentage of patients requiring intraoperative blood
      transfusion in the MIE group (23.4%) was significantly lower (P < 0.001) than in
      the open TTE (73.1%) and THE (67.7%) groups. The volume of intraoperative blood
      product transfusion was significantly lower for the MIE patients (median = 0 ml)
      than for the open TTE (median = 700 ml) and THE (median = 700 ml) patients. The
      incidence of respiratory complications with MIEs (10.64%) was significantly lower
      than with open TTEs (34.61%) and THEs (32.26%). The groups did not differ
      significantly in terms of R0 resection rates, OS, DFS, or QOL. CONCLUSIONS: MIEs
      offer a safe and viable alternative to open esophagectomies because they reduce
      the need and volume of intraoperative blood product transfusion and postoperative
      respiratory complications without compromising oncological clearance, survival,
      and QOL.

PMID- 21853395
TI  - Reply to letter to the editor: Re: Comparison of COX-2, Ki-67, and BCL-2
      expression in normal esophageal mucosa, Barrett's esophagus, dysplasia, and
      adenocarcinoma with postablation mucosa and implications for ablative therapies
      (Online First).

PMID- 21853396
TI  - Effects of Roux-en-Y operations on glucose homeostasis in obese GK rats.
AB  - AIM: To investigate the therapeutic effects of different styles of gastric bypass
      surgery on type 2 diabetes mellitus (T2DM) GK rats. METHODS: Twenty 6-8-week-old
      male GK rats were randomly divided into four groups: group A was operated by Roux
      en-Y gastrojejunostomy with duodenum exclusion and stomach capacity maintenance,
      group B was operated by loop-type gastrojejunostomy with duodenum exclusion and
      stomach capacity maintenance, group C was operated by Roux-en-Y gastrojejunostomy
      with partial gastrectomy, and group D was operated by loop-type gastrojejunostomy
      with partial gastrectomy. Changes of fasting blood glucose, oral glucose
      tolerance test (OGTT), and insulin tolerance test (ITT) in different operations
      were detected. RESULTS: The operations exerted good effects on controlling blood
      glucose in groups A, B, C, and D. There was no significant difference between
      groups A and C (P > 0.05) or between groups B and D (P > 0.05), while operations
      in groups A and C were more effective than groups B and D (P < 0.05). On the 21st
      day after surgery, OGTT in animals of groups A and C was significantly improved,
      as indicated by a 34% reduction in the area under the curve (AUC) for blood
      glucose (P < 0.05 versus groups B and D); pregavage insulin levels (ng/ml) were
      significantly decreased in groups A and C (P < 0.05 versus groups B and D). The
      insulin tolerance test (ITT) confirmed impaired insulin sensitivity in groups B
      and D, compared with groups A and C. CONCLUSIONS: Gastric bypass surgery might be
      effective to treat type 2 diabetes mellitus (T2DM), and Roux-en-Y
      gastrojejunostomy might be more effective than other operative styles.

PMID- 21853397
TI  - E-cadherin can be expressed by a small population of rat undifferentiated
      spermatogonia in vivo and in vitro.
AB  - Spermatogonial stem cells (SSCs) maintain gamete production in the testes
      throughout adult life by balancing self-renewal and differentiation. In vitro
      culture of SSCs is a crucial technique for gene manipulation of SSCs to generate
      transgenic animals, for transplantation of SSCs to restore male fertility for
      infertile man, and for generation of pluripotent stem cells from SSCs to
      differentiate into various cell lineages. Isolation of highly purified SSCs is an
      all-important component for development of these techniques. However, definitive
      markers for SSCs, which purify SSCs (100% enrichment), are unknown. SSCs of many
      species can colonize the mouse testis; thus, we reasoned that same molecules of
      SSCs are conserved between species. In mouse, undifferentiated spermatogonia
      express the surface marker E-cadherin. The hypothesis tested in this work was
      that E-cadherin (also known as CDH1) can be expressed by undifferentiated
      spermatogonia of rat testes. In this paper, cross-section immunohistochemistry
      and whole-mount immunohistochemistry of rat seminiferous tubules were conducted
      to show that E-cadherin-positive cells were small in number and there are single,
      paired, and aligned spermatogonia attached along the basement membrane. During in
      vitro culture period, the undifferentiated rat spermatogonial colonies co
      expressed E-cadherin and glial-derived neurotrophic factor family receptor alpha
      1 or E-cadherin and promyelocytic leukemia zinc finger. Data collected during the
      study demonstrate that E-cadherin is expressed by a small population of rat
      undifferentiated spermatogonia both in vivo and during in vitro culture period.

PMID- 21853399
TI  - Who receives food stamps during adulthood? Analyzing repeatable events with
      incomplete event histories.
AB  - Using data from the Panel Study of Income Dynamics (PSID) from 1968 to 2005, we
      estimate the cumulative probability that young adults in the United States will
      receive food stamps during adulthood, and examine how that probability varies
      with an individual's income and education at age 25 as well as by race and
      gender. We find that the probability of first food stamp receipt as an adult
      declines sharply with age, indicating that most adult recipients do so by age 40.
      Also, those receiving food stamps in early adulthood are likely to receive them
      again. For these reasons, and because food stamp receipt is a repeatable event,
      life table analyses that include individuals who are not observed until after
      they become exposed to the risk of food stamp receipt (whom we label "late
      entrants") are likely to overstate cumulative participation during adulthood. For
      example, one often-cited study included individuals who enter their sample after
      age 20 (late entrants) and report that 50.8% of 20-year-olds are recipients by
      age 65. In contrast, when we exclude late entrants, we find that 39.2% of 20-year
      olds and 29.7% of 25-year-olds receive benefits during adulthood.

PMID- 21853398
TI  - Optimization of human Th17 cell differentiation in vitro: evaluating different
      polarizing factors.
AB  - Regarding discrepancies that exist among different studies which have tried to
      clarify critical factors in human Th17 cell differentiation, the aim of this
      study was to identify the best condition for human Th17 differentiation and to
      clarify the possible role of TGF-beta in differentiation of these cells. Naive
      CD4(+) T cells were isolated from cord blood samples and cultured either in X
      VIVO 15 serum-free medium or RPMI 1640 containing 10% FBS. Purified cells were
      treated with different combinations of polarizing cytokines (TGF-beta, IL-1beta,
      IL-6, IL-23 and IL-21) followed by analysis of the expression of characteristic
      genes and their relevant cytokines by real-time quantitative RT-PCR and ELISA
      method, respectively. Our data indicate that a combination of TGF-beta plus IL-6
      and IL-23 cytokines in X-VIVO 15 serum-free medium could be applied as the best
      condition for developing human Th17 cells in compare with other studied cytokine
      treatments. It is shown that TGF-beta could be considered as a positive regulator
      for human Th17 cell differentiation only if applied in average concentrations.
      Interestingly, polarizing treatments in absence of TGF-beta, induced double
      secreting Th17 cells which co-express IL-17 and IFN-gamma whereas polarization in
      presence of TGF-beta-induced single-secreting (only IL-17 expressing) Th17 cells.

PMID- 21853400
TI  - Estimating the effect of the one-child policy on the sex ratio imbalance in
      China: identification based on the difference-in-differences.
AB  - In China, the male-biased sex ratio has increased significantly. Because the one
      child policy applies only to the Han Chinese but not to minorities, this unique
      affirmative policy allows us to identify the causal effect of the one-child
      policy on the increase in sex ratios by using a difference-in-differences (DD)
      estimator. Using the 1990 census, we find that the strict enforcement of the one
      child policy led to 4.4 extra boys per 100 girls in the 1980s, accounting for
      about 94% of the total increase in sex ratios during this period. The robust
      tests indicate that the estimated policy effect is not likely confounded by other
      omitted policy shocks or socioeconomic changes. Moreover, we conduct the DD
      estimation using both the 2000 census and the 2005 mini-census. Our estimates
      suggest that the one-child policy resulted in about 7.0 extra boys per 100 girls
      for the 1991-2005 birth cohorts. The effect of the one-child policy accounts for
      about 57% and 54% of the total increases in sex ratios for the 1991-2000 and 2001
      2005 birth cohorts, respectively.

PMID- 21853401
TI  - Bilateral calf augmentation for aesthetic purposes.
AB  - BACKGROUND: The shape of the calf is determined by the development of the soleus
      and gastrocnemius muscles, the length and orientation of the crural bones, and
      the distribution of subcutaneous fat. Some people have a naturally thin or
      underdeveloped calf that remains small despite exercise. Calf augmentation is
      indicated for cosmetic reasons or for reconstruction of a shrunken lower leg
      resulting from injury, illness, or congenital disability. METHODS: A total of 53
      consecutive patients (40 women and 13 men) had surgery for calf augmentation
      between January 2004 and January 2007. The patients ranged in age from 25 to 51
      years (mean, 29.5 years). All the patients included in the study requested calf
      augmentation for aesthetic purposes. Asymmetric-base silicone elastomer smooth
      surface implants were used. Overall satisfaction after silicone calf augmentation
      was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5
      (excellent). All the patients had surgery by the same team of surgeons (L.H.P.,
      A.S., B.N.). The evaluation was made at follow-up office consultations after 1
      year. The total mean follow-up time was 4.4 years. RESULTS: In this study, 53
      bilateral calf augmentations were performed, for a total of 106 procedures. The
      125-ml implant was used in 37 bilateral cases, the 70-ml implant in 10 cases; and
      the 175-ml implant in 6 cases. In three cases, unilateral seroma formation needed
      to be drained by a partial skin incision opening. There were no cases of
      infection or hematoma. Hypertrophic scar was observed in four patients
      bilaterally. One patient requested removal of the implants, and the procedure was
      performed on an outpatient basis. There were no cases of compartment syndrome or
      deep vein thrombosis, and no pulmonary embolisms occurred. There were no cases of
      rotation or displacement of the implant. At 12 months, 73% of the patients rated
      their appearance after calf augmentation as "very good" to "excellent," and 19%
      responded that their appearance was "good." Only 8% of the patients thought their
      appearance was less than good. At this writing, the average follow-up time for
      this group of patients has been 3.4 years. CONCLUSION: Calf augmentation by
      silicone-filled implants for cosmetic purposes appears to be effective, safe, and
      aesthetically pleasing, with minor side effects.

PMID- 21853403
TI  - Preservation of the nasal valve area with a lateral crural hinged flap: a
      cadaveric study.
AB  - BACKGROUND: Overresection of the lateral crura of the lower lateral cartilages is
      referred to as the most common cause of nasal valve collapse after rhinoplasty.
      The modern approach to functional rhinoplasty recognizes the importance of the
      tip framework's structural integrity and preserves tip support. METHODS:
      Traditional cephalic resections of lateral crura were performed on one side of
      five adult cadaver noses. On the opposite sides, hinged flaps of lateral crura
      were created. The noses were cross-sectioned at or near the internal nasal valve
      level, and the difference between the two sides was described. RESULTS: The study
      findings demonstrated improvement in the postoperation nasal valve area of the
      hinged flap side compared with the cephalic trim side. CONCLUSIONS: This
      preliminary study showed that the hinged flap is an option in nasal tip reduction
      surgery that may provide improved long-term aesthetic and functional outcomes
      through preservation of the nasal valve area.

PMID- 21853402
TI  - Large-volume liposuction and prevention of type 2 diabetes: a preliminary report.
AB  - This report presents a preliminary study investigating the effects of large
      volume liposuction on the parameters that determine type 2 diabetes. The study
      enrolled 31 patients with a body mass index (BMI) exceeding 30 kg/m(2) over a 1
      year period. All the liposuction procedures were performed with the patient under
      local anesthesia using ketamine/valium sedation. Pre- and postoperative blood
      pressure, fasting glucose, glycosylated hemoglobin (HbA1C), weight, and BMI were
      evaluated for 16 of the 30 patients who returned for a follow-up visit 3 to 12
      months postoperatively. The average aspirate was 8,455 ml without dermolipectomy
      and 5,795 ml with dermolipectomy. The data reveal a trend of improvement in blood
      sugar levels associated with weight loss that helps the patients. The average
      blood sugar level dropped 18% in our return patients, and the average weight loss
      was 9.2%. The average drop in BMI was 6.2%, and HbA1C showed a decrease of 2.3%.
      The patients with the best weight loss had the best reduction in blood sugar
      level and blood pressure. No transfers to the hospital and no thromboebolism
      occurred for any of the 31 patients. One dehiscence, two wound infections, and
      three seromas were reported. The authors hypothesize that large-volume
      liposuction in their series may have motivated some to diet, which could be
      explored in a larger series with control groups. Liposuction alone did not
      improve obesity but helped to motivate some of the patients to lose weight. These
      patients had the best results.

PMID- 21853404
TI  - Simultaneous augmentation mastopexy: a technique for maximum en bloc skin
      resection using the inverted-T pattern regardless of implant size, asymmetry, or
      ptosis.
AB  - BACKGROUND: Simultaneous augmentation mastopexy for moderately to severely ptotic
      breasts presents the challenge of determining how much excess skin should be
      removed after implant placement to create symmetry and provide for maximal skin
      tightening without compromising tissue vascularization. METHODS: Simultaneous
      augmentation mastopexy involves invagination and tailor tacking of the excess
      skin after implant placement and then making a pattern around the tailor-tacked
      tissues for previsualization of the total area to be resected. This contrasts
      with first making a pattern for the mastopexy, resecting the skin, and then
      tailor tacking the tissues together. Over a 7-year period, 55 women had
      simultaneous augmentation mastopexy with this approach. Saline implants were
      placed in the subpectoral dual-plane position before the mastopexy was started.
      All surgeries were performed with the patient under general anesthesia, and the
      patients were discharged the same day. In a retrospective chart review, breast
      implant size, degree of preoperative asymmetry, length of procedure, and
      complications were recorded. The patient follow-up period ranged from 3 months to
      7 years (median, 9 months). RESULTS: Symmetric, aesthetic results were achieved
      for all the patients. The range of saline implants used was 375-775 ml (average,
      500 ml). Of the 55 women, 15 had two different size implants measuring at least
      50 ml or larger, with the greatest size disparity in a patient being 225 ml (left
      breast, 700 ml; right breast, 475 ml). Six of the patients (10.9%) had small
      areas that healed by secondary intention, occurring mostly at the inferior
      junction of the inverted T. Only two patients (3.6%) had recurrence of breast
      ptosis, and only one patient (1.8%) had a mildly hypertrophic scar. There were no
      incidences of hematoma, infection, rippling, malposition of the nipple-areolar
      complex (NAC), NAC loss, capsular contraction, implant malposition, or
      dissatisfaction with implant size. The bilateral augmentation/mastopexy surgery
      time ranged from 2 h and 29 min to 4 h and 30 min (average, 3 h and 8 min).
      CONCLUSIONS: The described technique maximizes the amount of tissue to be
      resected in simultaneous augmentation mastopexy for moderately to severely ptotic
      breasts. Symmetry is more easily achieved with this approach regardless of the
      implant size used or the amount of skin to be resected. This technique minimizes
      the chance of tissue necrosis from devascularized skin edges. It also may shorten
      the inverted T scar and reduce the operative time.

PMID- 21853405
TI  - Scarpa fascia or rectus fascia in abdominoplasty flap elevation: a prospective
      clinical trial.
AB  - BACKGROUND: Postoperative seroma formation remains the most frequent complication
      after full abdominoplasty. This study aimed to evaluate postoperatively the
      formation of a minor seroma when the superficial fascia is used for preparation.
      METHODS: The study enrolled 50 patients who underwent a full abdominoplasty with
      umbilicus transposition between February 2008 and February 2010. The patients
      were alternated to the scarpa group or the rectus group. RESULTS: The two groups
      differed in terms of postoperative seroma formation and amount of average drain
      output. CONCLUSION: Scarpa fascia preservation seems to reduce postoperative
      seroma formation. The mechanism of the decreased fluid collection is not clear
      and needs further investigation.

PMID- 21853406
TI  - Thrombotic thrombocytopenic purpura after prophylactic cefuroxime axetil
      administered in relation to a liposuction procedure.
AB  - Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is
      characterized by platelet and von Willebrand factor (vWF) deposition in
      arterioles and capillaries throughout the body, which results in organ ischemia.
      The diagnostic pentad characterizing TTP consists of thrombocytopenia,
      microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and
      renal insufficiency. In terms of type, TTP can be either idiopathic or secondary.
      The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen
      vascular disease, cancer, bone marrow transplantation, and drugs (including
      cephalosporins). Postoperative TTP has been reported after vascular surgery,
      renal and liver transplantations, and orthopedic, urologic, and abdominal
      surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the
      mortality rates, but sometimes patients may have to receive immunosuppressive
      drugs including vincristine (VCR). This report describes a 42-year-old woman with
      TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction
      procedure who was treated successfully with plasma exchange and VCR. The patient
      fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP
      still is in remission after 6 months of follow-up evaluation. To the authors'
      knowledge, this is the first report in the literature describing a patient with
      TTP after cefuroxime axetil administered in relation to a surgical procedure who
      was treated successfully with TPE and VCR.

PMID- 21853407
TI  - New nipple-sharing technique that preserves the anatomic structure of the donor
      nipple for breastfeeding.
AB  - BACKGROUND: Although nipple-sharing in unilateral breast reconstruction is no
      longer a new technique, it offers the potential for an excellent match with the
      contralateral natural nipple. It also is particularly useful for cases in which a
      local flap elevation for nipple reconstruction likely would lead to
      complications. However, the established nipple-sharing techniques cannot be
      applied to patients who wish to preserve breastfeeding functionality even if the
      technique would otherwise be considered favorable. To overcome this obstacle, the
      authors devised a new nipple-sharing technique that does not damage the anatomic
      structure of the donor nipple for breastfeeding. This report presents this new
      technique as an option for nipple reconstruction. METHODS: The new technique
      consists of harvesting tissue by the circumcision method of nipple reduction and
      grafting the tissue in a spiral configuration. RESULTS: The reported technique
      has been performed for nine patients. All the reconstructed nipples have retained
      their projection and their suitability as matches for the contralateral nipples
      throughout a maximum follow-up period of 5 years. CONCLUSIONS: The new technique
      allows nipple-sharing to be applied while preserving the anatomic structure of
      the donor nipple for breastfeeding.

PMID- 21853408
TI  - Combining CAT with cognitive diagnosis: a weighted item selection approach.
AB  - Computerized adaptive testing (CAT) was originally proposed to measure theta,
      usually a latent trait, with greater precision by sequentially selecting items
      according to the student's responses to previously administered items. Although
      the application of CAT is promising for many educational testing programs, most
      of the current CAT systems were not designed to provide diagnostic information.
      This article discusses item selection strategies specifically tailored for
      cognitive diagnostic tests. Our goal is to identify an effective item selection
      algorithm that not only estimates theta efficiently, but also classifies the
      student's knowledge status alpha accurately. A single-stage item selection method
      with a dual purpose will be introduced. The main idea is to treat diagnostic
      criteria as constraints: Using the maximum priority index method to meet these
      constraints, the CAT system is able to generate cognitive diagnostic feedback in
      a fairly straightforward fashion. Different priority functions are proposed. Some
      of them are based on certain information measures, such as Kullback-Leibler
      information, and others utilize only the information provided by the Q-matrix. An
      extensive simulation study is conducted, and the results indicate that the
      information-based method not only yields higher classification rates for
      cognitive diagnosis, but also achieves more accurate theta estimation. Other
      constraint controls, such as item exposure rates, are also considered for all the
      competing methods.

PMID- 21853409
TI  - The Lexical Stroop Sort (LSS) picture-word task: a computerized task for
      assessing the relationship between language and executive functioning in school
      aged children.
AB  - The relationship between language development and executive function (EF) in
      children is not well understood. The Lexical Stroop Sort (LSS) task is a
      computerized EF task created for the purpose of examining the relationship
      between school-aged children's oral language development and EF. To validate this
      new measure, a diverse sample of school-aged children completed standardized oral
      language assessments, the LSS task, and the widely used Dimensional Change Card
      Sort (DCCS; Zelazo, 2006) task. Both EF tasks require children to sort stimuli
      into categories based on predetermined rules. While the DCCS largely relies on
      visual stimuli, the LSS employs children's phonological loop to access their
      semantic knowledge base. Accuracy and reaction times were recorded for both
      tasks. Children's scores on the LSS task were correlated with their scores on the
      DCCS task, and a similar pattern of relationships emerged between children's
      vocabulary and the two EF tasks, thus providing convergent validity for the LSS.
      However, children's phonological awareness was associated with their scores on
      the LSS, but not with those on the DCCS. In addition, a mediation model was used
      to elucidate the predictive relationship between phonological awareness and
      children's performance on the LSS task, with children's vocabulary fully
      mediating this relationship. The use of this newly created and validated LSS task
      with different populations, such as preschoolers and bilinguals, is also
      discussed.

PMID- 21853410
TI  - R squared effect-size measures and overlap between direct and indirect effect in
      mediation analysis.
AB  - In a recent article in this journal (Fairchild, MacKinnon, Taborga & Taylor,
      2009), a method was described for computing the variance accounted for by the
      direct effect and the indirect effect in mediation analysis. However, application
      of this method leads to counterintuitive results, most notably that in some
      situations in which the direct effect is much stronger than the indirect effect,
      the latter appears to explain much more variance than the former. The explanation
      for this is that the Fairchild et al. method handles the strong interdependence
      of the direct and indirect effect in a way that assigns all overlap variance to
      the indirect effect. Two approaches for handling this overlap are discussed, but
      none of them is without disadvantages.

PMID- 21853411
TI  - Thermotolerance and molecular chaperone function of the small heat shock protein
      HSP20 from hyperthermophilic archaeon, Sulfolobus solfataricus P2.
AB  - Small heat shock proteins are ubiquitous in all three domains (Archaea, Bacteria
      and Eukarya) and possess molecular chaperone activity by binding to unfolded
      polypeptides and preventing aggregation of proteins in vitro. The functions of a
      small heat shock protein (S.so-HSP20) from the hyperthermophilic archaeon,
      Sulfolobus solfataricus P2 have not been described. In the present study, we used
      real-time polymerase chain reaction analysis to measure mRNA expression of S.so
      HSP20 in S. solfataricus P2 and found that it was induced by temperatures that
      were substantially lower (60 degrees C) or higher (80 degrees C) than the optimal
      temperature for S. solfataricus P2 (75 degrees C). The expression of S.so-HSP20
      mRNA was also up-regulated by cold shock (4 degrees C). Escherichia coli cells
      expressing S.so-HSP20 showed greater thermotolerance in response to temperature
      shock (50 degrees C, 4 degrees C). By assaying enzyme activities, S.so-HSP20 was
      found to promote the proper folding of thermo-denatured citrate synthase and
      insulin B chain. These results suggest that S.so-HSP20 promotes thermotolerance
      and engages in chaperone-like activity during the stress response.

PMID- 21853412
TI  - Antibiotic resistance pattern among the Salmonella isolated from human, animal
      and meat in India.
AB  - The present study was conducted to study the antibiotic resistance pattern among
      nontyphoidal Salmonella isolated from human, animal and meat. A total of 37
      Salmonella strains isolated from clinical cases (human and animal) and meat
      during 2008-2009 belonging to 12 serovars were screened for their antimicrobial
      resistance pattern using 25 antimicrobial agents falling under 12 different
      antibiotic classes. All the Salmonella isolates tested showed multiple drug
      resistance varying from 5.40% to 100% with 16 of the 25 antibiotics tested. None
      of the isolates were sensitive to erythromycin and metronidazole. Resistance was
      also observed against clindamycin (94.59%), ampicillin (86.49%), co-trimoxazole
      (48.65%), colistin (45.94%), nalidixic acid (35.10%), amoxyclave (18.90%),
      cephalexin, meropenem, tobramycin, nitrofurantoin, tetracycline, amoxicillin
      (8.10% each), sparfloxacin and streptomycin (5.40% each). Isolates from clinical
      cases of animals were resistant to as many as 16 antibiotics, whereas isolates
      from human clinical cases and meat were resistant to 9 and 14 antibiotics,
      respectively. Overall, 19 resistotypes were recorded. Analysis of multiple
      antibiotic resistance index (MARI) indicated that clinical isolates from animals
      had higher MARI (0.25) as compared to isolates from food (0.22) and human (0.21).
      Among the different serotypes studied for antibiogram, Paratyhi B isolates,
      showed resistance to three to 13 antibiotics, whereas Typhimurium strains were
      resistant to four to seven antibiotics. Widespread multidrug resistance among the
      isolates from human, animal and meat was observed. Some of the uncommon serotypes
      exhibited higher resistance rate. Considerable changes in the resistance pattern
      were also noted. An interesting finding was the reemergence of sensitivity to
      some of the old antibiotics (chloromphenicol, tetracycline).

PMID- 21853413
TI  - Analysis of umbu (Spondias tuberosa Arruda (Anacardiaceae)) in different
      landscape management regimes: a process of incipient domestication?
AB  - Plant domestication is an evolutionary process guided by human groups who modify
      the landscape for their needs. The objective of this study was to evaluate the
      phenotypic variations between populations of Spondias tuberosa Arruda (umbuzeiro)
      when subjected to different local landscape management strategies. The influence
      of the landscape management system on these populations was evaluated in five
      identified regional units (mountains, base of mountains, pastures, cultivated
      areas and home gardens). Ten individuals were randomly selected from each region
      and subjected to morphological and chemical fruit analysis. The diversity index,
      based on Simpson's index, was determined for the different populations. We then
      evaluated the morphological differences between the individual fruits from the
      distinct landscape areas. We observed no significant differences in morphological
      diversity between the areas studied. Our data suggest that the umbuzeiro
      specimens in this region may be in the process of incipient domestication.

PMID- 21853414
TI  - Assessment of water quality along a recreational section of the Damour River in
      Lebanon using the water quality index.
AB  - Considering that water is becoming progressively scarce, monitoring water quality
      of rivers is a subject of ongoing concern and research. It is very intricate to
      accurately express water quality as water quantity due to the various variables
      influencing it. A water quality index which integrates several variables in a
      specific value may be used as a management tool in water quality assessment.
      Moreover, this index may facilitate communication with the public and decision
      makers. The main objectives of this research project are to evaluate the water
      quality index along a recreational section of a relatively small Mediterranean
      river in Southern Lebanon and to characterize the spatial and temporal
      variability. Accordingly, an assessment was conducted at the end of the dry
      season for a period of 5 years from 2005 to 2009. The estimated water quality
      index classified the average water quality over a 5-year period at the various
      sites as good. Results revealed that water quality of the Damour River is
      generally affected by the anthropogenic activities taking place along its
      watershed. The best quality was found in the upper sites and the worst at the
      estuary. The presence of fecal coliform bacteria in very high levels may indicate
      potential health risks to swimmers. This study can be used to support the
      evaluation of management, regulatory, and monitoring decisions.

PMID- 21853415
TI  - Family interaction in pediatric diabetes.
AB  - Adaptation to type 1 diabetes is optimized in the presence of ongoing family
      support and supervision. Therefore, it is particularly important to understand
      how family interactions influence adaptation to the illness. The purpose of this
      paper is to review the current literature on family interaction in youth with
      type 1 diabetes. Recent advancements in the literature include greater
      specificity of types of parental involvement, attention to the role of fathers,
      acknowledgment of the impact of parental distress, increased use of observational
      methods, and awareness of the impact of culture. Continued parental involvement
      particularly monitoring-in the management of diabetes care is important as
      children transition into adolescence, and the best outcomes are evident when this
      involvement occurs in a warm, collaborative manner. Parents need support in
      managing their own distress to maintain this type of involvement.

PMID- 21853416
TI  - Urinary tract infections in patients with spinal cord injuries.
AB  - Spinal cord injuries (SCI) result in different lower urinary tract dysfunctions.
      Because of both the disease and the bladder drainage method, urinary tract
      infections (UTIs) are one of the most frequent conditions seen in SCI patients.
      Diagnosis is not always easy due to lack of symptoms. Asymptomatic bacteriuria
      needs no treatment. If symptoms occur, antibiotherapy is indicated. Duration
      depends mainly on severity of illness and upper urinary tract or prostatic
      involvement. Choice of antibiotherapy should be based on local resistance
      profiles, but fluoroquinolones seems to be an adequate empirical treatment.
      Prevention of UTI is important, as lots of complications can be foreseen.
      Catheter care, permanent low bladder pressure and clean intermittent
      catheterization (CIC) with hydrophilic catheters are interventions that can
      prevent UTI. Probiotics might be useful, but data are limited.

PMID- 21853418
TI  - Esophagogastrostomy using a circular stapler in laparoscopy-assisted proximal
      gastrectomy with an incision in the left abdomen.
AB  - PURPOSE: Recently, the frequency of early gastric cancer in the upper third of
      the stomach has especially increased. We have improved the esophagogastrostomy
      procedure to maximize the preservation of physiologic functions. METHODS: Eleven
      patients were reconstructed by esophagogastrostomy with an incision in the left
      abdomen after limited proximal gastrectomy. We presented here the details of this
      reconstructive method and demonstrated the results of postoperative evaluations
      of the lower esophagus and the remaining stomach. RESULTS: Median surgical
      duration and blood loss was 330 min and 32 ml for this procedure. The approach
      using circular stapler from the left side allowed a good laparoscopic visual
      field to be obtained for the plane of the esophagogastrostomy. The reconstructive
      procedure was successfully performed without intraoperative complications. There
      were no anastomosis-related postoperative complications encountered in ten
      patients, but delayed anastomotic stenosis occurred in one patient. This
      technique preserved the lower esophageal sphincter as well as peristalsis of the
      lower stomach and also allowed the greater curvature near the top of the stomach
      to function as a new fundus. The incidence of reflux esophagitis on endoscopic
      examination was limited. CONCLUSIONS: This approach for esophagogastrostomy with
      an incision in the left abdomen could be a simple, easy, and safe reconstructive
      technique after laparoscopy-assisted proximal gastrectomy with preservation of
      maximal physiologic function of the remnant stomach.

PMID- 21853419
TI  - Improved in vitro cultivation of endothelial progenitor cells as basis for dermal
      substitutes with enhanced angiogenic capabilities.
AB  - PURPOSE: Endothelial progenitor cells (EPCs) are a promising cell source for
      vascular tissue engineering approaches in surgery. Diverse biomaterials have been
      used as matrices for EPC cultivation. In this in vitro study, fibrin in
      combination with growth factors was examined as an optimized culturing scaffold
      for EPCs. METHODS: EPCs were isolated from peripheral blood by density gradient
      centrifugation and positive selection using CD34-specific magnetic beads. Cells
      were seeded on fibrin for 3, 5, and 10 days or on fibronectin for control
      purposes. The growth factors erythropoietin (EPO), granulocyte-monocyte colony
      stimulating factor (GM-CSF), and hepatocyte growth factor were added as
      indicated. Cell proliferation and integrity measurements were performed, and EPC
      differentiation was determined by fluorescence-activated cell sorting (FACS)
      analysis. RESULTS: EPCs cultured on fibrin showed a significantly higher
      proliferation rate and suffered less from matrix-induced cell death compared to
      EPCs cultured on fibronectin. Additionally, fibrin was a stronger stimulus for
      the differentiation of EPCs into a mature endothelial phenotype, as revealed by
      the expression of adult endothelial markers by FACS analysis. Moreover, EPO and
      GM-CSF enhanced EPC proliferation and differentiation to a greater extent when
      EPCs were grown on fibrin. CONCLUSIONS: We conclude that EPC cultivation on
      fibrin is superior compared to the commonly used fibronectin as a scaffold for
      tissue engineering of vascular structures. The addition of different growth
      factors, reported to stimulate EPC growth, further improves the beneficial
      effects of this matrix.

PMID- 21853420
TI  - Open tension-free hernioplasty using a novel lightweight self-gripping mesh:
      medium-term experience from two institutions.
AB  - PURPOSE: The process of mesh fixation and the potential risk of associated
      chronic pain are always surgeon's main concerns in hernia surgery. A wide variety
      of lightweight mesh models are currently available on the market to overcome some
      of these problems showing good preliminary results, but no data representing the
      medium- or long-term results. The present study aims to report the clinical
      outcomes of two institutional series of patients who underwent hernia repair
      using a partially absorbable auto adherent mesh (ParieteneTM ProgripTM--PP).
      METHODS: A prospective analysis was performed including unselected patients with
      primary groin hernia who underwent a standardized Lichtenstein procedure using
      the PP mesh at two tertiary institutions. RESULTS: During the 2-year study
      period, 181 patients (167 males; 14 females) with a median age of 63 years (19-85
      years) were operated on at both centers. Short-term complications occurred in 27
      patients (15%), the most commonly seen being urinary retention (6%) followed by
      hematoma (5%) and acute orchitis (2%). With a median follow-up of 17 months (12
      29 months), 4 patients (2%) had a feeling of a foreign body in the groin, and 7
      (4%) developed chronic pain. A total of four patients (2%) developed recurrence.
      CONCLUSIONS: In our experience, the use of the PP mesh for hernioplasties offers
      a potential benefit not only in the short-term period but also in a medium-term
      follow-up with low recurrence and late chronic pain rates. However, this
      particular mesh does not fully prevent all complications and chronic pain and
      recurrent hernias have been reported for the first time.

PMID- 21853421
TI  - Influenza-related excess mortality, Austria 2001 till 2009.
AB  - In Austria, a country with a total population of approximately 8.3 million, the
      published estimates of influenza-associated deaths within the past decade are
      surprisingly high (up to 6000 deaths per year) when compared to neighbouring
      countries. The objective of our analysis was to provide reliable estimates of the
      annual influenza-related deaths in Austria. We estimated the seasonal influenza
      related excess mortality by calculating the difference between all-cause
      mortality observed during the influenza season and the baseline values to be
      expected during that time span if increased influenza activity was absent.
      Increased influenza activity was defined as moderate, usual or high, categorized
      by the influenza activity index using weekly data from the Austrian sentinel
      clinical surveillance system. For obtaining estimates of baseline all-cause
      mortality, a cyclic regression model was applied to the time series data on
      weekly all-cause mortality from 2001 to 2009. Austrian seasonal influenza-related
      excess mortality peaked in the seasons 2002/2003 (1060 excess deaths), 2004/2005
      (1102 excess deaths) and 2008/2009 (1192 excess deaths). The rising trend
      observed is in parallel with the increasing proportion of the Austrian population
      older than 65 years for the same time span (2001:15.5%; 2009: 17.5%). Our
      findings on seasonal influenza-related excess mortality are in accordance with
      the estimates from Germany and Switzerland, which were derived from a similar
      approach. In order to gain and to preserve higher compliance with influenza
      vaccination initiatives, it is essential to have reliable data on influenza
      related mortality. Thus, the numbers presented so far by Austrian public health
      institutions must be challenged.

PMID- 21853422
TI  - Structural and functional imaging correlates of cognitive and brain reserve
      hypotheses in healthy and pathological aging.
AB  - In the field of ageing and dementia, brain- or cognitive reserve refers to the
      capacity of the brain to manage pathology or age-related changes thereby
      minimizing clinical manifestations. The brain reserve capacity (BRC) hypothesis
      argues that this capacity derives from an individual's unique neural profile
      (e.g., cell count, synaptic connections, brain volume, etc.). Complimentarily,
      the cognitive reserve (CR) hypothesis emphasizes inter-individual differences in
      the effective recruitment of neural networks and cognitive processes to
      compensate for age-related effects or pathology. Despite an abundance of
      research, there is scarce literature attempting to synthesize the BRC the CR
      models. In this paper, we will review important aging and dementia studies using
      structural and functional neuroimaging techniques to investigate and attempt to
      assimilate both reserve hypotheses. The possibility to conceptualize reserve as
      reflecting indexes of brain plasticity will be proposed and novel data suggesting
      an intimate and complex correspondence between active and passive components of
      reserve will be presented.

PMID- 21853423
TI  - Incidental brain lesions in children: to treat or not to treat?
AB  - Central nervous system (CNS) lesions that are discovered incidentally when
      imaging children for problems that were unrelated to the detected lesion pose a
      dilemma to physicians. Because there are few data on the outcome of such cases,
      we retrospectively reviewed the clinical course of a group of children followed
      at our institution with brain lesions found incidentally on neuro-imaging. A
      database of all children with brain lesions followed at the University of
      Rochester medical center from 2000 to 2010 was reviewed. Data were obtained
      regarding presentation, magnetic resonance imaging (MRI) features, treatment,
      progression-free survival, and overall survival of children with brain lesions
      found incidentally. Of the 244 children with brain lesions seen over this time
      period, 21 (8.6%) were found to have incidentally discovered brain lesions. Of
      these 21 children, 12 (57%) underwent surgical resection of their brain lesions.
      Ten patients (48%) had symptoms considered to be unassociated with the detected
      lesion. Lesions were found in the cerebellum (n = 7, 33%), midline (n = 5, 24%),
      and cerebrum (n = 9, 43%). All lesions were <=5 cm in diameter. Eight patients
      (38%) had surgery at presentation, one because of imaging features suspicious for
      a posterior fossae ependymoma, and the seven others because of location in the
      posterior fossae or brain stem. Of the remaining 13 patients, five had
      progression of disease on serial MRI scans: four underwent surgery and the fifth
      was monitored and remained stable after the initial progression stabilized. Nine
      of the ten patients (90%) with posterior fossae lesions underwent surgery, while
      only three of 11 with supratentorial lesions underwent surgery (27%) (P = 0.006).
      The progression free survival was 94% at 12 months (95% CI 65-99%) and 71% at 24
      months (95% CI 39-88%). At a median follow-up of 32 months, the overall survival
      was 100%. Incidentally detected CNS lesions are usually small. The outcome for
      children with such lesions is excellent. Close monitoring of these patients with
      serial MRIs may be a safe alternative to immediate biopsy and/or resection for
      select patients.

PMID- 21853424
TI  - Cell phones and glioma risk: a review of the evidence.

PMID- 21853425
TI  - The role of antifungal therapy in the prevention of recurrent allergic fungal
      rhinosinusitis after functional endoscopic sinus surgery: a randomized,
      controlled study.
AB  - Allergic fungal rhinosinusitis (AFRS) is the most common form of fungal sinus
      disease. Its recurrence rate is high despite numerous strategies to prevent it.
      We conducted a study to assess the effect of systemic and topical antifungal
      agents-both separately and in combination-in preventing recurrence of AFRS
      following functional endoscopic sinus surgery (FESS). Our initial study
      population was made up of 50 adults who were diagnosed with AFRS by clinical,
      radiologic, histopathologic, and laboratory workup and who subsequently underwent
      FESS. Postoperatively, these patients were randomized into 5 different treatment
      groups matched for sex, age, and socioeconomic status. Four of the groups
      received a different antifungal regimen in addition to convenient medical
      treatment (CMT), while a fifth group served as a control. The antifungal regimens
      included oral itraconazole (group A), fluconazole nasal spray (group B), combined
      oral itraconazole and nasal fluconazole (group C), and irrigation with a
      fluconazole solution through the nasal fossa (group D); the group of 10 controls
      (group E) received CMT only. A total of 41 patients were available for follow-up
      (9 mo maximum). Recurrence rates in the 5 groups were 66.7, 10.0, 14.3, 28.6, and
      75.0%, respectively. Based on our findings, we conclude that treatment with
      topical fluconazole as either a nasal spray or an irrigation solution can
      significantly reduce the rate of recurrence of AFRS after FESS.

PMID- 21853426
TI  - Papillary squamous cell carcinoma of the larynx.
AB  - Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma of
      the aerodigestive tract that has been correlated with a more favorable prognosis
      than conventional squamous cell carcinoma of the head and neck. In this report,
      the authors present a case of papillary squamous cell carcinoma and a review of
      the literature on this topic.

PMID- 21853427
TI  - Utility of panendoscopy for the detection of unknown primary head and neck cancer
      in patients with a negative PET/CT scan.
AB  - We conducted a retrospective review of the records of 23 patients who had been
      diagnosed with regionally metastatic head and neck squamous cell carcinoma from
      an unknown primary tumor. Our goal was to assess the utility of panendoscopy in
      locating the primary tumor in those patients whose positron-emission
      tomography/computed tomography (PET/CT) findings were negative. Overall, we found
      that PET/CT had correctly identified the unknown primary in 12 of the 23 patients
      (52%); panendoscopy confirmed this finding in all 12. Of the remaining 11
      patients, however, panendoscopy located the primary tumor in only 1 (9%). In this
      era of cost containment and ongoing advances in imaging and transnasal
      esophagoscopy, it is important to revisit the workup of an unknown primary in
      patients with a negative PET/CT scan. There are various advantages and
      disadvantages to performing panendoscopy with biopsy in patients with an unknown
      primary and a negative PET/CT scan, but our results and the findings of others
      indicate that it will detect the primary in only about 10% of these cases. We
      recommend careful selection of patients who are to undergo panendoscopy for the
      routine workup of an unknown primary.

PMID- 21853428
TI  - Return to contact sports following infectious mononucleosis: the role of serial
      ultrasonography.
AB  - Splenic rupture is a rare but potentially fatal complication of infectious
      mononucleosis. Athletes returning to contact sports following infectious
      mononucleosis are at potential risk of splenic rupture secondary to abdominal
      trauma. No clear consensus exists as to when it is safe to allow these athletes
      to return to contact sports. Suggested periods of abstinence have ranged from 2
      weeks to 6 months. We outline our experiences with the use of abdominal
      ultrasonography at 1 month after the diagnosis of infectious mononucleosis as a
      means of determining when athletes can safely return to contact sports. Our study
      group was made up of 19 such patients (mean age: 16.7 yr). We found that 16 of
      these patients (84%) had normal splenic dimensions on ultrasonography 1 month
      after diagnosis, and they were therefore allowed to return to contact sports.
      While the remaining 3 patients had an enlarged spleen at 1 month, their splenic
      dimensions had all returned to normal when ultrasonographic examination was
      repeated at 2 months postdiagnosis. We conclude that serial abdominal
      ultrasonography allows for informed decision making in determining when athletes
      can safely return to contact sports following infectious mononucleosis.

PMID- 21853429
TI  - Eccrine porocarcinoma of the external ear.
AB  - Eccrine porocarcinoma (EP) is believed to arise from the intraepithelial portion
      of the eccrine sweat glands. The incidence rate of EP is reported to be 18 per
      450,000 biopsies. Most of the diagnosed cases involve the lower extremities; a
      case of EP involving the ear is rare. We describe the clinical, radiologic, and
      histopathologic features of EP in an 11-year-old boy.

PMID- 21853430
TI  - Delayed facial nerve palsy after endolymphatic sac surgery.
AB  - Data on delayed facial nerve palsy (DFNP) following endolymphatic sac enhancement
      surgery are limited. We conducted a retrospective chart review to determine the
      incidence, possible predisposing factors, treatment, and prognosis of DFNP in
      such cases. We reviewed the records of 779 patients who had undergone
      endolymphatic sac surgery for intractable Meniere disease from January 1997
      through December 2007 at a tertiary care otologic referral center. We found 5
      cases (0.64%) of postoperative DFNP. The length of time between surgery and the
      onset of DFNP ranged from 7 to 20 days (mean: 11). Paralysis was incomplete in
      all 5 patients. Four of these patients had an abnormal mastoid bone anatomy, as
      the sigmoid sinus was either anteriorly or anteromedially displaced. The 5
      patients had been treated with a steroid, either with or without an antiviral,
      and all 5 experienced a complete recovery of facial nerve function within 8 weeks
      of the onset of their paralysis. It is difficult to delineate the exact etiology
      of DFNP following endolymphatic sac surgery, but we speculate that factors such
      as physical injury to the nerve and/or a viral reactivation might have played a
      role. Also, the unusual mastoid bone anatomy seen in 4 of these patients might
      have been responsible, as well.

PMID- 21853431
TI  - Nonattendance at a hospital-based otolaryngology clinic: a preliminary analysis
      within a universal healthcare system.
AB  - Missed appointments at specialty clinics generate concerns for physicians and
      clinic administrators. Appointment nonattendance obstructs the provision of
      timely medical interventions and the maximization of systemic efficiencies. Yet,
      empiric study of factors associated with missed appointments at adult specialty
      clinics has received little attention in North America. We conducted a
      preliminary study of otolaryngology clinic nonattendance in the context of a
      universal healthcare system environment in Canada. Our data were based on the
      schedule of 1,512 new patient appointments at a hospital-based clinic from May 1
      through Sept. 30, 2008. Gathered information included the employment status of
      the attending physician (i.e., full-time vs. part-time), the patient's sex and
      age, the day of the week and the time of the appointment, and the attendance
      status. We found that the rate of nonattendance was 24.4% (n = 369).
      Nonattendance rates varied significantly according to physician employment status
      (more common for part-time physicians), patient sex (women) and age (younger
      adults), and the day of the appointment (Wednesdays), but not according to the
      time of day. Our findings suggest that there are predictable patient and systemic
      factors that influence nonattendance at medical appointments. Awareness of these
      factors can have implications for the delivery of healthcare services within a
      universal healthcare context.

PMID- 21853432
TI  - Aneurysm of the internal carotid artery in the middle ear.

PMID- 21853433
TI  - Characteristics of nasal injuries incurred during sports activities: analysis of
      91 patients.
AB  - Nasal injuries are among the most common sports injuries. We conducted a
      prospective, observational study of 91 patients, aged 7 to 60 years (mean: 18.3),
      who had sustained a nasal injury while engaging in a sport, exercise, or other
      recreational physical activity. We found that a substantial proportion of these
      injuries occurred in females (29.7% of cases). A high percentage of injuries
      (86.8%) occurred in those who had been participating in a noncontact sport; the
      sport most often implicated was basketball (26.4%). Also, injuries were more
      common during organized competition as opposed to recreational play (59.3 vs.
      40.7%). Of the 91 nasal injuries, 59 (64.8%) were fractures, most of which were
      treated with a closed reduction. Almost all of the patients in this study (92.3%)
      were able to return to their sport. We conclude that most sports-related nasal
      fractures are not preventable.

PMID- 21853434
TI  - Women in otolaryngology-head and neck surgery.

PMID- 21853435
TI  - Endoscopic view of frontal sinus discharge following balloon dilation.

PMID- 21853436
TI  - Papilloma: a diagnostic near miss.

PMID- 21853437
TI  - An unusual presentation of an asymptomatic neck mass.

PMID- 21853438
TI  - Giant esophageal inlet patch.

PMID- 21853439
TI  - External ear sarcoma: a review of the Surveillance Epidemiology and End Result
      (SEER 17) database.
AB  - Soft-tissue sarcomas arising in the skin of the external ear have a better
      prognosis than might be expected based on the behavior of other sarcomas.
      Currently there are a few major case series analyzing soft-tissue sarcomas and
      the factors related to their prognosis. The purpose of this study was to
      determine the behavior of these tumors and attempt to define factors affecting
      prognosis. We extracted data from the Surveillance Epidemiology and End Result
      (SEER) 17 Registry and identified a total of 297 patients with sarcoma of the
      external ear who were included in the registry from 1973 to 2004. Of these, 176
      (59.3%) patients were diagnosed with malignant fibrous histiocytoma.
      Dermatofibrosarcoma was the second most prevalent soft-tissue sarcoma (56
      patients; 18.9%), followed by leiomyosarcoma (27 patients; 9.1%). The overall 5
      year survival rate of patients with all histologic types of STS of the external
      ear was 78.5%.

PMID- 21853440
TI  - Congenital fixation of the head of the stapes in three family members.
AB  - We conducted a retrospective chart review at a university hospital on a family
      that exhibited a rare cause of conductive hearing loss. Four male patients of
      this family had congenital conductive hearing loss. Three of these family members
      underwent bilateral ossiculoplasty, a father and two of his three sons. All three
      were found to have mild or moderate conductive hearing loss due to fixation of
      the head of the stapes by a bony bar that extended from the head of the stapes to
      the posterior ear canal wall. Surgical removal of the bony bar improved hearing
      in all cases. This family exhibits autosomal-dominant inheritance of this
      abnormality. Fixation of the head of the stapes by a bony bar that extends to the
      posterior ear canal wall is a rare cause of congenital, autosomal-dominant, mild
      or moderate conductive hearing loss that can be surgically corrected.

PMID- 21853441
TI  - Changes in intramaxillary sinus pressure following antrostomy, draining tubes,
      and YAMIK procedures in 25 patients treated for chronic paranasal sinusitis.
AB  - When conservative therapies are not effective in treating sinus infections,
      alternate steps can be taken to improve paranasal cavity ventilation. These
      measures may include surgical procedures such as intranasal endoscopic or
      maxillary sinus fenestration, and other procedures such as placement of a
      maxillary sinus tube or a YAMIK sinus catheter. We conducted a prospective study
      of 25 patients to investigate the effects on the nasal mucosa of improved
      ventilation between the nasal and paranasal cavities. We accomplished this by
      comparing (1) the results of simultaneously measured nasal cavity and
      intramaxillary sinus pressures before and after widening of ventilation openings,
      (2) changes in mucociliary transport function as measured by the saccharin test,
      and (3) changes in nasal airway resistance. Just as multiple transit routes
      between the nasal cavity and maxillary sinus give rise to greater fluctuations in
      intramaxillary sinus pressure, and just as rapid breathing gives rise to even
      greater pressure fluctuations than does quiet breathing, we believe that both
      intranasal cavity airflow velocity and the number of ventilation openings present
      have an effect on the state of ventilation between the nasal cavity and maxillary
      sinus. We also suggest that the establishment of maxillary sinus ventilation
      openings improves mucociliary clearance.

PMID- 21853442
TI  - The role of point-of-care CT in the management of chronic rhinosinusitis: a case
      control study.
AB  - Point-of-care computed tomography (POC-CT) has become more feasible since the
      introduction of smaller imaging devices that deliver lower radiation doses. As
      the availability of this modality continues to increase, its impact on diagnostic
      and therapeutic algorithms in patients with chronic rhinosinusitis (CRS) must be
      evaluated. We conducted a study of 40 consecutively presenting new patients who
      (1) met the symptom criteria for CRS but whose endoscopy results were negative
      (i.e., no pus, polyps, or edema), (2) had not undergone any previous CT scanning
      or sinus surgery, and (3) had undergone POC-CT during their initial evaluation. A
      comparison group was made up of 40 patients from the pre-POC-CT era whose initial
      treatment had been based on the history alone; these patients underwent CT after
      their medical therapy had been completed. In the pre-POC-CT group, follow-up CT
      showed evidence of inflammatory disease in 24 patients (60%), 13 of whom (54.2%)
      had received an antibiotic at their initial visit, including 2 who had received
      an oral steroid, as well; among the 16 patients whose follow-up CT was negative,
      only 2 (12.5%) had received an antibiotic, neither of whom received an oral
      steroid. In the POC-CT group, 27 of 40 patients (67.5%) had positive findings at
      the initial visit, and 14 of them (51.9%) received an antibiotic and an oral
      steroid; none of the 13 patients in whom POC-CT was negative was prescribed
      either agent. Thus, the incidence of scan positivity and antibiotic use was
      similar in the two cohorts. Also, patients who met the symptomatic definition of
      CRS but who were lacking in objective endoscopic findings were more likely to
      have received an oral steroid when POC-CT was part of the initial assessment;
      these patients were also less likely to be lost to follow-up. Ongoing prospective
      studies will better characterize the magnitude of these effects on long-term
      outcomes, antibiotic resistance, healthcare costs, and overall quality of care.

PMID- 21853443
TI  - Approach to benign tumors of the palate: analysis of 28 cases.
AB  - We conducted a retrospective analysis of 28 patients-15 men and 13 women, aged 17
      to 71 years (mean: 41.6)-who had undergone surgery for the treatment of a benign
      tumor of the hard or soft palate. The most common chief complaint was a palatal
      mass, which was reported by 14 patients (50.0%). Tumors were more common in the
      hard palate than in the soft palate by a margin of 23 to 5 (82.1 to 17.9%; p =
      0.001). The most common histopathologic diagnosis was pleomorphic adenoma, which
      occurred in 9 cases (32.1%). Most patients were treated with local excision with
      clear margins, which was sufficient in almost all cases, as there were only 2
      recurrences, both of which occurred in men with a hard-palate pleomorphic
      adenoma. For these 2 patients, a wider excision and repair with palatal islet
      flaps was performed, and no further recurrence or malignant transformation was
      observed during follow-up. Two patients with a soft-palate hemangioma were
      treated with an intralesional steroid injection and radiofrequency ablation,
      which reduced the size of their lesion considerably.

PMID- 21853444
TI  - Management of lateral cervical metastases in papillary thyroid cancer: patterns
      of lymph node distribution.
AB  - In this article we discuss the management of lateral cervical lymph node
      metastases in papillary thyroid cancer (PTC). We conducted a retrospective
      analysis of cases of PTC at our tertiary academic medical center involving 32
      patients who underwent 39 neck dissections for the management of lateral cervical
      metastases from 2000 to 2007. Of these patients, 18 underwent primary neck
      dissections at the time of thyroidectomy after fine-needle aspiration biopsy
      confirmed the PTC. Secondary neck dissections for delayed metastases were
      performed in 14 patients who had previously undergone thyroidectomy for confirmed
      PTC. All 32 patients had positive nodes in at least one level. Our results
      highlight the high incidence of multilevel cervical metastasis associated with
      PTC and suggest the importance of including level II-B (submuscular recess) when
      performing a neck dissection; the upper posterior triangle (level V-A) is less
      likely to harbor occult tumor. Lateral neck metastasis from PTC is common and
      predictable; locoregional control is improved with a formal, comprehensive neck
      dissection at the time of thyroidectomy.

PMID- 21853445
TI  - Identification and assessment of new biomarkers for colorectal cancer with serum
      N-glycan profiling.
AB  - BACKGROUND: The objectives of this study were to identify and validate the
      diagnostic value of N-glycan markers in colorectal cancer (CRC) and to uncover
      their underlying molecular mechanism. METHODS: In total, 347 individuals,
      including patients with CRC, patients with colorectal adenoma, and healthy
      controls, were divided randomly into a training group (n = 287) and retrospective
      validation groups (n = 60). Serum N-glycan profiling was analyzed by DNA
      sequencer-assisted/flurophore-assisted carbohydrate electrophoresis (DSA-FACE).
      Two diagnostic models were constructed based on N-glycan profiling with logistic
      stepwise regression. The diagnostic performance of each model was assessed
      further in retrospective, prospective (n = 43), and follow-up (n = 46) cohorts.
      Lectin blot and reverse transcriptase-polymerase chain reaction were used to
      analyze the total core-fucosylated residues and molecular expression involved in
      core-fucosylation modifications in CRC. RESULTS: Two diagnostic models designated
      CRCglycoA and CRCglycoB were constructed to differentiate CRC from normal and
      adenoma, respectively. The areas under the receiver operating characteristic
      curves (AUC) of both CRCglycoA and CRCglycoB were higher than the AUC of
      carcinoembryonic antigen (CEA) (CRCglycoA, 0.92 vs 0.81; CRCglycoB, 0.81 vs
      0.73). The sensitivity and accuracy of CRCglycoA improved from 21.7% to 25% and
      from 11.63% to 18% in the training cohort, the retrospective cohort, and the
      prospective cohorts compared with the sensitivity and accuracy of CEA. The
      sensitivity of CRCglycoB improved from 20% to 28.23%. Both altered N-glycans, and
      results from the diagnostic models were reversed after curative surgery. The
      level of total core fucose residues and fucosyltransferase were decreased
      significantly in CRC. CONCLUSIONS: The current results indicated that the N
      glycan markers based diagnostic models are new, valuable, noninvasive
      alternatives for identifying CRC. The authors concluded that decreased
      fucosyltransferase may be responsible for decreased levels of total core
      fucosylated modification in both tissues and serum from patients with CRC.

PMID- 21853446
TI  - A high-throughput dielectrophoresis-based cell electrofusion microfluidic device.
AB  - A high-throughput cell electrofusion microfluidic chip has been designed,
      fabricated on a silicon-on-insulator wafer and tested for in vitro cell fusion
      under a low applied voltage. The developed chip consists of six individual
      straight microchannels with a 40-MUm thickness conductive highly doped Si layer
      as the microchannel wall. In each microchannel, there are 75 pairs of counter
      protruding microelectrodes, between which the cell electrofusion is performed.
      The entire highly doped Si layer is covered by a 2-MUm thickness aluminum film to
      maintain a consistent electric field between different protruding microelectrode
      pairs. A 150-nm thickness SiO2 film is subsequently deposited on the top face of
      each protruding microelectrode for better biocompatibility. Owing to the short
      distance between two counter protruding microelectrodes, a high electric field
      can be generated for cell electrofusion with a low voltage imposed across the
      electrodes. Both mammalian cells and plant protoplasts were used to test the cell
      electrofusion. About 42-68% cells were aligned to form cell-cell pairs by the
      dielectrophoretic force. After cell alignment, cell pairs were fused to form
      hybrid cells under the control of cell electroporation and electrofusion signals.
      The averaged fusion efficiency in the paired cells is above 40% (the highest was
      about 60%), which is much higher than the traditional polyethylene glycol method
      (<5%) and traditional electrofusion methods (~12%). An individual cell
      electrofusion process could be completed within 10 min, indicating a capability
      of high throughput.

PMID- 21853447
TI  - A novel concept of dielectrophoretic engine oil filter.
AB  - A novel concept of an alternating current (AC) dielectrophoretic filter with a
      three-dimensional electrode array is presented. A filter is constructed by
      winding into layers around the core tube two sheets of woven metal wire-mesh with
      several sheets of woven insulating wire-mesh sandwiched in between. Contrary to
      conventional dielectrophoretic devices, the proposed design of electrodes
      generates a high-gradient field over a large working volume by applying several
      hundred volts at a standard frequency of 60 Hz. The operating principle of
      filtration is based on our recently developed method of AC dielectrophoretic
      gating for microfluidics. The filtration efficiency is expressed in terms of two
      non-dimensional parameters, which describe the combined influence of the particle
      polarizability and size, the oil viscosity and flow rate, and the field gradient
      on the particle captivity. The proof-of-concept is tested by measuring the single
      pass performance of two filters on positively polarized particles dispersed in
      engine oil: spherical glass beads, fused aluminum oxide powder, and silicon metal
      powder, all smaller than the mesh opening. The results obtained are used to
      consider the potential of using AC dielectrophoretic filtration and provide
      critical design guidelines for the development of a filter based on the retention
      capability of challenge particles.

PMID- 21853448
TI  - Insulator-based dielectrophoresis of microorganisms: theoretical and experimental
      results.
AB  - Dielectrophoresis (DEP) is the motion of particles due to polarization effects in
      nonuniform electric fields. DEP has great potential for handling cells and is a
      non-destructive phenomenon. It has been utilized for different cell analysis,
      from viability assessments to concentration enrichment and separation. Insulator
      based DEP (iDEP) provides an attractive alternative to conventional electrode
      based systems; in iDEP, insulating structures are used to generate nonuniform
      electric fields, resulting in simpler and more robust devices. Despite the rapid
      development of iDEP microdevices for applications with cells, the fundamentals
      behind the dielectrophoretic behavior of cells has not been fully elucidated.
      Understanding the theory behind iDEP is necessary to continue the progress in
      this field. This work presents the manipulation and separation of bacterial and
      yeast cells with iDEP. A computational model in COMSOL Multiphysics was employed
      to predict the effect of direct current-iDEP on cells suspended in a microchannel
      containing an array of insulating structures. The model allowed predicting
      particle behavior, pathlines and the regions where dielectrophoretic
      immobilization should occur. Experimental work was performed at the same
      operating conditions employed with the model and results were compared, obtaining
      good agreement. This is the first report on the mathematical modeling of the
      dielectrophoretic response of yeast and bacterial cells in a DC-iDEP microdevice.

PMID- 21853449
TI  - No effects of short-term exposure to mobile phone electromagnetic fields on human
      cognitive performance: a meta-analysis.
AB  - During recent years, a large number of studies on the effects of electromagnetic
      fields emitted by cellular mobile phones on human cognitive performance have been
      carried out. However, the results have been ambiguous. We carried out the current
      meta-analysis in order to investigate the impact of electromagnetic fields
      emitted by mobile phones on human cognition. Seventeen studies were included in
      the meta-analysis as they fulfill several requirements such as single- or double
      blind experimental study design, and documentation of means and standard
      deviations of dependent variables. The meta-analysis was carried out as a group
      comparison between exposed and non-exposed subjects. No significant effects of
      electromagnetic fields emitted by Global System for Mobile Communications (GSM)
      and Universal Mobile Telecommunications System (UMTS) mobile phones were found.
      Cognitive abilities seem to be neither impaired nor facilitated. Results of the
      meta-analysis suggest that a substantial short-term impact of high frequency
      electromagnetic fields emitted by mobile phones on cognitive performance can
      essentially be ruled out.

PMID- 21853450
TI  - Altered development of Xenopus embryos in a hypogeomagnetic field.
AB  - The hypogeomagnetic field (HGMF; magnetic fields <200 nT) is one of the
      fundamental environmental factors of space. However, the effect of HGMF exposure
      on living systems remains unclear. In this article, we examine the biological
      effects of HGMF on the embryonic development of Xenopus laevis (African clawed
      frog). A decrease in horizontal third cleavage furrows and abnormal morphogenesis
      were observed in Xenopus embryos growing in the HGMF. HGMF exposure at the two
      cell stage, but no later than the four-cell stage, is enough to alter the third
      cleavage geometry pattern. Immunofluorescent staining for alpha-tubulin showed
      reorientation of the spindle of four-cell stage blastomeres. These results
      indicate that a brief (2-h) exposure to HGMF is sufficient to interfere with the
      development of Xenopus embryos at cleavage stages. Also, the mitotic spindle
      could be an early sensor to the deprivation of the geomagnetic field, which
      provides a clue to the molecular mechanism underlying the morphological and other
      changes observed in the developing and/or developed embryos.

PMID- 21853451
TI  - Orthology prediction methods: a quality assessment using curated protein
      families.
AB  - The increasing number of sequenced genomes has prompted the development of
      several automated orthology prediction methods. Tests to evaluate the accuracy of
      predictions and to explore biases caused by biological and technical factors are
      therefore required. We used 70 manually curated families to analyze the
      performance of five public methods in Metazoa. We analyzed the strengths and
      weaknesses of the methods and quantified the impact of biological and technical
      challenges. From the latter part of the analysis, genome annotation emerged as
      the largest single influencer, affecting up to 30% of the performance. Generally,
      most methods did well in assigning orthologous group but they failed to assign
      the exact number of genes for half of the groups. The publicly available
      benchmark set (http://eggnog.embl.de/orthobench/) should facilitate the
      improvement of current orthology assignment protocols, which is of utmost
      importance for many fields of biology and should be tackled by a broad scientific
      community.

PMID- 21853452
TI  - Recent application of analytical methods to phase I and phase II drugs
      development: a review.
AB  - Drug development is a time-consuming and costly process. It is usually divided
      into four phases, although it is not always possible to draw a sharp line between
      the various stages. In phase I and II there are many molecules investigate and it
      is necessary to analyze all of them in a short period of time, with lower costs,
      and with high-throughput assay. During phase I relevant chemical-physical
      parameters like the acid dissociation constant, lipophilicity, solubility and
      stability must be analyzed. Classic techniques such as 'shake-flask' can be used,
      but instrumental analytical methods such as HPLC may be helpful to improve and
      enhance the productivity and reproducibility of the results. During phase II the
      activity of a drug and factors that may have an influence on it, like metabolic
      profile and transformations, impurities and plasma biding proteins, must be
      considered. In this field, recent hyphenated analytical methods, such as LC
      MS/MS, GC-MS/MS or more complex couplings, can provide more complete information.
      The aim of this review is to report the processes required for the validation of
      drug efficacy with reference to the description of 'classic' and modern
      techniques used.

PMID- 21853455
TI  - Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9
      nuclear translocalization in inner meniscus cells.
AB  - The meniscus plays an important role in controlling the biomechanics of the knee.
      However, the mechanical stress-related response in meniscus cells remains
      unclear. We investigated mechanical stretch-regulated gene expression in human
      meniscus cells. Human inner and outer meniscus cells were prepared from the inner
      and outer halves of the lateral meniscus. The gene expressions of Sry-type HMG
      box (SOX) 9 and alpha1(II) collagen (COL2A1) were assessed by real-time PCR
      analyses after cyclic tensile strain (CTS) treatment (0.5 Hz, 5% stretch). The
      localization and phosphorylation of SOX9 were evaluated by immunohistochemical
      and Western blot (WB) analyses. Chromatin immunoprecipitation (IP) analysis was
      performed to assess the stretch-related protein-DNA complex formation between
      SOX9 and the COL2A1 enhancer on chromatin. Type II collagen deposition and SOX9
      production were detected only in inner menisci. CTS treatments increased
      expression of the COL2A1 and SOX9 genes in inner meniscus cells, but not in outer
      meniscus cells. In addition, CTS treatments stimulated nuclear translocalization
      and phosphorylation of SOX9 in inner meniscus cells. Chromatin IP analyses
      revealed that CTS increased the association between SOX9 and its DNA-binding
      site, included in the COL2A1 enhancer, on chromatin. Our results indicate that
      inner and outer meniscus cells have different properties in mechanical stretch
      induced COL2A1 expression. In inner meniscus cells, mechanical stretch may have
      an essential role in the epigenetic regulation of COL2A1 expression.

PMID- 21853456
TI  - Augmentation of peri-implant bone improves implant stability: quantification
      using simulated bone loss.
AB  - Low bone quality, such as induced by osteoporosis, is considered a main factor
      leading to failure of fracture fixations. Peri-implant bone augmentation has been
      proposed as a means of reducing failure rates in osteoporotic bone by improving
      implant stability. The beneficial effects of pharmacological augmentation of bone
      in the immediate vicinity of the implant have been demonstrated. Yet, a
      quantitative understanding of the role of peri-implant bone in implant stability
      is lacking. Therefore, the aim of our study was to quantify the effects of bone
      loss and peri-implant bone augmentation on implant stability using image-based
      finite element analyses. Using a validated model, we simulated how osteoporotic
      bone loss would affect implant stability in human humeral heads. We also
      quantified how augmentation of peri-implant bone can enhance implant stability.
      Our simulations revealed that a 30% reduction in bone mass led to a 50% decrease
      in implant stability. We also found that peri-implant bone augmentation increased
      implant stability and that the efficiency of bone augmentation decreased with
      increasing peri-implant distance. These findings highlight the strong effect that
      bone loss has on implant fixation and the potential of peri-implant bone
      augmentation for improving implant anchorage in low quality bone.

PMID- 21853457
TI  - Passive mechanical properties and related proteins change with botulinum
      neurotoxin A injection of normal skeletal muscle.
AB  - The effects of botulinum neurotoxin A on the passive mechanical properties of
      skeletal muscle have not been investigated, but may have significant impact in
      the treatment of neuromuscular disorders including spasticity. Single fiber and
      fiber bundle passive mechanical testing was performed on rat muscles treated with
      botulinum neurotoxin A. Myosin heavy chain and titin composition of single fibers
      was determined by gel electrophoresis. Muscle collagen content was determined
      using a hydroxyproline assay. Neurotoxin-treated single fiber passive elastic
      modulus was reduced compared to control fibers (53.00 kPa vs. 63.43 kPa). Fiber
      stiffness and slack sarcomere length were also reduced compared to control fibers
      and myosin heavy chain composition shifted from faster to slower isoforms.
      Average titin molecular weight increased 1.77% after treatment. Fiber bundle
      passive elastic modulus increased following treatment (168.83  kPa vs. 75.14
      kPa). Bundle stiffness also increased while collagen content per mass of muscle
      tissue increased 38%. Injection of botulinum neurotoxin A produces an effect on
      the passive mechanical properties of normal muscle that is opposite to the
      changes observed in spastic muscles.

PMID- 21853458
TI  - Combined microwave irradiation and intraarticular glutamine administration
      induced HSP70 expression therapy prevents cartilage degradation in a rat
      osteoarthritis model.
AB  - The objective of the present study was to investigate the effects of heat
      stimulation and glutamine (Gln) on the expression of extracellular matrix genes
      and heat shock protein 70 (HSP70) in rat articular cartilage in vivo and to
      determine whether HSP70 expression achieved with a combination of microwave (MW)
      and Gln suppresses osteoarthritis (OA) progression in a rat OA model. Stimulation
      at 40 W was assumed to be appropriate in the present study, and the effects of
      heat treatment at this intensity were evaluated. Articular cartilage was
      collected at 8 h after heat stimulation and/or intraarticular Gln administration,
      and total RNA was extracted. The expression of HSP70, aggrecan, and type II
      collagen was quantified using real-time RT-PCR. Cartilage samples from the OA
      model were subjected to hematoxylin and eosin (HE) and safranin O staining. HSP70
      and aggrecan expression was greatest in a group receiving both MW and Gln. In the
      rat OA model, the severity of OA was significantly milder in a group receiving MW
      and Gln than in the control group. HSP70, stimulated by the combination of MW
      heat and Gln, may be involved in the suppression of OA progression.

PMID- 21853459
TI  - The gliding characteristics of the flexor pollicis longus tendon in the carpal
      tunnel: potential implications for manual pipette users.
AB  - To understand the potential mechanism for hand and wrist complaints in pipette
      users, whose motion is characterized by repetitive thumb motion in certain wrist
      positions, the peak (PGR) and mean (MGR) gliding resistance of the flexor
      pollicis longus (FPL) tendon were measured in nine human cadaver wrists. The PGR
      with the wrist in 30 degrees  ulnar deviation and in the neutral position were
      significantly lower than the PGR with the wrist in 60 degrees  flexion. The MGR
      with the wrist in 30 degrees  ulnar deviation was significantly lower than the
      MGR with the wrist in 60 degrees  flexion, 60 degrees  extension, or 20 degrees 
      radial deviation with 40 degrees  extension. Based on these data, we believe that
      a manual pipette designed to be used in neutral to ulnar deviated wrist position
      could have ergonomic advantages.

PMID- 21853460
TI  - Thoughts on human variations.

PMID- 21853461
TI  - James Drake (1667-1707): Anatomist and political activist.
AB  - James Drake (1667-1707) was a renowned physician, anatomist, and writer whose
      name was recognized throughout London. He was highly involved in the politics of
      his time and was a well-known pamphleteer. He also delved into comedies and
      plays. Drake became a fellow of the Royal Society and the College of Physicians
      before his early death at 40 years of age. He authored one of the most deservedly
      popular medical treatises of his time, Anthropologia Nova, which remained a
      valuable resource to physicians and anatomists alike for decades. The present
      article reviews the contributions of this little known name in the history of
      anatomy.

PMID- 21853462
TI  - The Thebesian valve: Gatekeeper to the coronary sinus.
AB  - Clinical cardiac procedures such as electrophysiology studies, catheter ablation
      of arrhythmias, retrograde cardioplegia delivery, cardiac resynchronization
      therapy and, more recently, percutaneous mitral annuloplasty, involve cannulation
      of the coronary sinus (CS). The presence of a membrane closing the orifice of the
      CS may cause difficulties during these interventions. Thus, detailed knowledge of
      the variations and anomalies of the valve of the CS, or the Thebesian valve, now
      has practical significance. To improve our understanding of this structure,
      classic anatomical dissection of 50 hearts from dissection room cadavers was
      performed. A Thebesian valve was present in the overwhelming majority (88%) of
      cases. Its morphology varied widely, from a few small strands of tissue, to a
      membrane covering more than half the CS ostium. A significant number (20%) of
      valves occluded >65% of the ostium, making them "potential complicating factors"
      in cannulation of the CS. An understanding of these anatomical variations may
      help in identifying and overcoming potential difficulties during clinical cardiac
      interventions.

PMID- 21853463
TI  - Re: Ronald A. Bergman, "Thoughts on human variation".

PMID- 21853464
TI  - Correlation between patella and patellar tendon width: An anatomic study.
AB  - Anterior cruciate ligament (ACL) rupture is a common injury among orthopaedic
      patients with many different treatment modalities including bone-patella-bone
      autograft (BPBA) ACL reconstruction. Patella tendon width has been reported to be
      a predictor of recovery speed and success following BPBA repair. This study
      reports on the strength of the relationship between patella width and patella
      tendon width. Twenty fresh frozen cadavers were included in the study. Patella
      and patellar tendon measurements were recorded at the midpoint of the patellar
      tendon. Pearson correlation and linear regression were used to determine the
      relationship between patella width and patellar tendon width. Bivariate
      correlations with 95% confidence intervals and coefficients of determination
      (R(2) ) are reported. The study used 20 cadavers, 12 men and 8 women with a mean
      age of 72 (standard deviation [SD] = 12; range = 44 to 87). The mean patella
      width was 49.24mm (SD = 4.11; range 42.33mm-56.33mm) while the mean patellar
      tendon width was 26.10mm (SD = 3.31; range 18.33mm-33.33mm). The correlation
      between patella width and patellar tendon width was 0.67 (95% confidence interval
      = 0.45 - 0.81). R(2), the percent of variance in patellar tendon width accounted
      for by patella width, was 0.45. The regression equation for predicting patellar
      tendon width (y) yielded a formula of y = 0.536 + -0.316 * patella width. A
      moderate correlation exists between patella width and patellar tendon width. Our
      data suggests that this correlation is strongest with wider patellas and is more
      loosely associated with smaller patellas.

PMID- 21853465
TI  - A reappraisal of the hypophysial region of the floor of the sella turcica.
AB  - While studying the detailed anatomy of the cranial sella turcica, an additional
      fossa in its floor, which has not previously been described, was noted. A survey
      for this fossa, therefore, was conducted on 205 adult crania from the Raymond A.
      Dart Collection of Human Skeletons, University of the Witwatersrand. To confirm
      the survey observations, the sella turcica region of 10 adult cadavers was also
      dissected. A larger anterior depression and a smaller posterior concave fossa,
      often extending on to the anterior surface of the dorsum sellae, were evident in
      the hypophysial region and occurred in 21.5% of crania and in six of the 10
      dissected specimens. An anterior depression alone or a posterior fossa alone
      occurred in 2.4% and in 72% of the crania, respectively, indicating that the
      posterior fossa occurs most commonly in this series. The more commonly occurring
      presence of a posterior fossa abutting on to the anterior surface of the dorsum
      sellae is described for the first time.

PMID- 21853466
TI  - Reply to "Thoughts on human variations".

PMID- 21853467
TI  - Neuromuscular partitioning in the extensor carpi radialis longus and brevis based
      on intramuscular nerve distribution patterns: A three-dimensional modeling study.
AB  - Differential activation of specific regions within a skeletal muscle has been
      linked to the presence of neuromuscular compartments. However, few studies have
      investigated the extra- or intramuscular innervation throughout the muscle volume
      of extensor carpi radialis longus (ECRL) and brevis (ECRB). The aim of this study
      was to determine the presence of neuromuscular partitions in ECRL and ECRB based
      on the extra- and intramuscular innervation using three-dimensional modeling. The
      extra- and intramuscular nerve distribution was digitized and reconstructed in 3D
      in all the muscle volumes using Autodesk Maya in seven formalin embalmed
      cadaveric specimens (mean age, 75.7 +/- 15.2 years). The intramuscular nerve
      distribution was modeled in all the muscle volumes. ECRL was found to have two
      neuromuscular compartments, superficial and deep. One branch from the radial
      nerve proper was found to innervate ECRL. This branch was divided into anterior
      and posterior branches to the superficial and deep compartments, respectively.
      Five innervation patterns were identified in ECRB with partitioning of the muscle
      belly into two, three, or four compartments, in a proximal to distal direction
      depending on the number of nerve branches entering the muscle belly. The ECRL and
      ECRB both demonstrated neuromuscular compartmentalization based on intramuscular
      innervation. According to the partitioning hypothesis, a muscle may be
      differentially activated depending on the required function of the muscle, thus
      allowing multifunctional muscles to contribute to a variety of movements.
      Therefore, the increased number of neuromuscular partitions in ECRB when compared
      with ECRL could be due to the need for more differential recruitment in the ECRB
      depending on force requirements.

PMID- 21853468
TI  - Topographical anatomy of the suprascapular nerve and vessels at the suprascapular
      notch.
AB  - Suprascapular nerve entrapment caused by the superior transverse scapular
      ligament (STSL) causes pain, and limitation of motion in the shoulder. To relieve
      these symptoms, suprascapular nerve decompression is performed through the
      resection of STSL. To describe and classify the topographic anatomy of the
      suprascapular notch, 103 cadaveric shoulders were dissected. The mean length and
      width of STSLs were 11.2 and 3.4 mm, respectively. The bony bridges replacing
      STSL in four shoulders were 8.2 mm long and 3.5 mm wide on average. The
      suprascapular nerve always ran through the notch under the STSL. All shoulders
      had a single suprascapular artery, while multiple suprascapular veins appeared in
      21.3%. The arrangement of the suprascapular vessels was classified into three
      types: in Type I (59.4%), all suprascapular vessels ran over the STSL; in Type II
      (29.7%), the vessels ran over and under the STSL simultaneously; in Type III
      (10.9%), all vessels ran under the STSL. In 48.9% of cadavers, these types were
      bilaterally matched. The omohyoid muscle originated distantly from the STSL in
      38.0%, was adjacent to it in 44.0%, and was partially over the STSL in 18.0%. The
      number of suprascapular vessels running under the STSL was positively correlated
      with the size of the STSL and the middle diameter of the suprascapular notch. Age
      was inversely correlated with the length of STSL. The STSL was wider in males
      than in females. This study provides details of the structural variations in the
      region of the suprascapular notch.

PMID- 21853469
TI  - Pathways for cervical metastasis in malignant neoplasms of the head and neck
      region.
AB  - There have been significant changes in the evaluation and management of lymphatic
      metastases in the neck during the past several decades, and knowledge of the
      functional anatomy of the cervical lymphatics is fundamental to the clinical
      management of metastasis in this region. This review provides a comprehensive
      description of the cervical lymphatics and discusses how this knowledge is used
      in the modern management of the neck lymphatics in the setting of common cancers
      of the head and neck. The patterns of tumor spread can be delineated based on the
      well-studied functional anatomy of the lymphatic networks in the cervical region.
      The characteristics and patterns of metastatic spread for two common cancers
      found in this region, squamous cell carcinoma and cutaneous malignant melanoma,
      are discussed in this review. Significant improvements in clinical care, namely,
      selective neck dissection and sentinel lymph node biopsy aided by
      lymphoscintigraphy, have been developed and are based upon detailed studies of
      the pathways of metastatic spread. These advances have significantly decreased
      the morbidity associated with the evaluation and treatment of metastatic disease
      to the neck.

PMID- 21853470
TI  - Aberrant penetrating posterior descending artery from proximal right coronary
      artery.
AB  - We report a rare variant of the posterior descending artery (PDA) in a 51-year
      old African-American male discovered in coronary CT angiography. Arising from the
      proximal right coronary artery near its ostium, the anomalous PDA penetrated
      posteriorly toward the atrioventricular junction septum, exited through the
      inferior pyramidal space into the posterior interventricular groove and continued
      in the groove as a short PDA. Along its course it gave rise to small branches to
      the medial wall of the right atrium, the atrioventricular node region, and the
      inferoseptal wall of the right ventricle.

PMID- 21853472
TI  - Reply: Sacralization is not associated with elongated cervical costal process and
      cervical rib.

PMID- 21853473
TI  - Branching pattern of the external branch of the superior laryngeal nerve and its
      clinical importance.
AB  - The external branch of the superior laryngeal nerve gives off many branches above
      the upper pole of the thyroid gland. Differentiating the branch innervating the
      cricothyroid muscle from the others may be important during surgery. Therefore,
      we aimed to demonstrate the branching pattern of this nerve in detail. In 34
      human cadavers (59 sides), branches of the nerve were exposed and measurements
      related to them and neighboring structures were made. A cricothyroidal branch was
      present on all sides. This branch pierced the inferior pharyngeal constrictor
      muscle 3.9-17.6 mm above, 3.1-9.9 mm below, or at the level of the upper pole of
      the thyroid gland. On all sides, the nerve provided one or two thyroidal
      branches. The thyroidal branch was generally thinner than the cricothyroidal
      branch. But they were equal in size on three (5%) sides. The external laryngeal
      nerve provided two or three pharyngeal branches on all sides. These branches
      arose from the nerve 3.5-12.7 mm from the upper pole of the thyroid gland.
      Although the branch was generally thinner than the cricothyroidal branch, both
      branches were equal on four (6.7%) sides. Two cardiac branches were observed on
      two (3.3%) left sides. In conclusion, the cricothyroidal branch was generally
      thicker than the other branches. But on seven (11.8%) sides, thyroidal or
      pharyngeal branches and the cricothyroidal branch were equal in size. These data
      may be important during surgery as the surgeon may confuse the cricothyroidal
      branch with other branches of the external laryngeal nerve.

PMID- 21853474
TI  - Stereodynamics and absolute configuration of stereolabile atropisomers in 2,2
      dimethyl-1-aryl-1-indanols.
AB  - We describe herein the investigation of the stereodynamic processes occurring in
      a series of 1-aryl-2,2-dimethylindanols, by dynamic NMR. When the aryl moiety is
      a mesityl or a 2-methyl-1-naphthyl, the rotational barrier exceeds the 25
      kcal/mol, so that stable atropisomers are observed. In two cases, all the chiral
      atropisomeric species have been separated by enantioselective HPLC, and the
      comparison between theoretical and experimental electronic circular dichroism
      spectra allowed the absolute configuration assignment of all the isolated species
      to be obtained.

PMID- 21853477
TI  - Tuning molecular recognition in water-soluble nanogels with enzyme-like activity
      for the kemp elimination.
AB  - The synthesis and characterization of water-soluble imprinted nanogels with
      enzyme-like activity in the Kemp elimination is reported together with studies
      that demonstrate how the recognition properties, morphology, and catalytic
      activity of the nanoparticles can be tuned by the use of surfactants, such as
      Tween 20. A detailed kinetic investigation is carried out, which shows clear
      evidence of saturation kinetics and rule out the effects of mass transfer. This
      is supported by characterization of the polymeric materials that confirms the
      morphological changes resulting from the use of surfactants. These results
      provide an important tool for the development of nanoparticle-based, new catalyst
      mimicking enzymes.

PMID- 21853478
TI  - Size-controllable gold-platinum alloy nanoparticles on nine functionalized ionic
      liquid surfaces and their application as electrocatalysts for hydrogen peroxide
      reduction.
AB  - A series of room-temperature ionic liquids (RTILs) containing different
      functional groups such as hydroxyl, nitrile, carboxyl, and thiol attached to
      imidazolium cations, combined with various anions such as chloride [Cl],
      tetrafluoroborate [BF(4)], hexafluorophosphate [PF(6)], and
      bis[(trifluoromethyl)sulfonyl]imide [Tf(2)N], have been successfully synthesized.
      Dissolved in chitosan (Chi), the Chi/RTIL composites can be employed as flexible
      templates for the preparation of Au/Pt nanostructures. These Au/Pt nanostructures
      can be facilely deposited in situ on the surface of Chi/RTILs through
      electrodeposition. Scanning electron microscopy (SEM) and atomic force microscopy
      (AFM) results demonstrate that the alloy size is significantly dependent on the
      structure of the Chi/RTILs, with sizes ranging from 2.8 to 84.7 nm. Based upon
      the functionalized RTILs, nine Chi/RTIL-Au/Pt biosensors have been fabricated.
      First, the size-dependent electrochemistry of Chi/RTIL-Au/Pt was investigated
      using potassium ferricyanide as the probe. The reversible electron transfer of
      the Fe(CN)(6)(3-/4-) redox couple was realized for the nine biosensors, and the
      peak currents, as well as the peak-to-peak separations (DeltaE(p)) and electron
      transfer rates, differ greatly from each other because of the diversity of the
      RTILs. Further electrochemical research reveals that the functional groups of
      these RTILs exert an evident influence on the reduction behavior of H(2)O(2),
      which in turn illustrates that the electrocatalytic activity of Chi/RTIL-Au/Pt
      nanocomposites can be tuned by means of employing RTILs with different functional
      groups, and an appropriate combination of cations and anions may produce a higher
      activity. The facilitated electron transfer and the intrinsic catalytic activity
      of Au/Pt NPs provide a facile way to construct a third-generation H(2)O(2)
      biosensor with a high sensitivity, low detection limit, quick response time, and
      excellent selectivity.

PMID- 21853476
TI  - Single nucleotide polymorphisms of matrix metallopeptidase 3 and risk of gliomas
      in a Chinese Han population.
AB  - Matrix metallopeptidases (MMPs) play an important role in central nervous system
      tumor growth, invasion and spreading. The currently available data provide clear
      evidence for the involvement of MMP3 in the pathophysiology of glioma. The study
      aims to explore the association of single nucleotide polymorphisms (SNPs) across
      the MMP3 gene with glioma risk. Three haplotype tagging and additional two
      promoter SNPs were genotyped among 766 glioma patients and 824 cancer-free
      controls from East China. None of these polymorphisms alone had a significant
      effect on risk of gliomas. However, when three promoter polymorphisms were
      evaluated together by the number of putative risk of genotypes (i.e., rs645419AA,
      632478CA+AA, rs522616AA), a statistically significantly increased risk of gliomas
      was associated with the combined genotypes with two to three risk genotypes,
      compared with those with zero to one risk genotypes (adjusted odds ratio (OR) =
      1.32; 95% confidence interval (CI) = 1.03-1.68). This increased risk was also
      more pronounced among adults (adjusted OR = 1.14, 95%CI = 1.02-1.27), males
      (adjusted OR = 1.19, 95%CI = 1.05-1.36), smokers (adjusted OR = 1.28, 95%CI =
      1.07-1.52), subjects with no family history of cancer (adjusted OR = 1.21, 95%CI
      = 1.07-1.37), and patients with nonastrocytic gliomas (adjusted OR = 1.23, 95%CI
      = 1.06-1.43). In summary, our results suggest that any one of MMP3 variants may
      not have a substantial effect on glioma risk, but a joint effect of MMP3 promoter
      polymorphisms may contribute to risk of gliomas, particularly for adult gliomas.

PMID- 21853475
TI  - UVB radiation-induced beta-catenin signaling is enhanced by COX-2 expression in
      keratinocytes.
AB  - UVB radiation is the major carcinogen responsible for skin carcinogenesis, thus
      elucidation of the molecular pathways altered in skin in response to UVB would
      reveal novel targets for therapeutic intervention. It is well established that
      UVB leads to upregulation of cyclooxygenase 2 (COX-2) in the skin which
      contributes to skin carcinogenesis. Overexpression of COX-2 has been shown to
      promote colon cancer cell growth through beta-catenin signaling, however, little
      is known about the connection between UVB, COX-2, and beta-catenin in the skin.
      In the present study, we have identified a novel pathway in which UVB induces
      beta-catenin signaling in keratinocytes, which is modulated by COX-2 expression.
      Exposure of the mouse 308 keratinocyte cell line (308 cells) and primary normal
      human epidermal keratinocytes (NHEKs) to UVB resulted in increased protein levels
      of both N-terminally unphosphorylated and total beta-catenin. In addition, we
      found that UVB-enhanced beta-catenin-dependent TOPflash reporter activity and
      expression of a downstream beta-catenin target gene. We demonstrated that UVB
      induced beta-catenin signaling is modulated by COX-2, as treatment of
      keratinocytes with the specific COX-2 inhibitor NS398 blocked UVB induction of
      beta-catenin. Additionally, beta-catenin target gene expression was reduced in
      UVB-treated COX-2 knockout (KO) MEFs compared to wild-type (WT) MEFs.
      Furthermore, epidermis from UVB-exposed SKH-1 mice exhibited increased N
      terminally unphosphorylated and total beta-catenin protein levels and increased
      staining for total beta-catenin, and both responses were reduced in COX-2
      heterozygous mice. Taken together, these results suggest a novel pathway in which
      UVB induces beta-catenin signaling in keratinocytes which is enhanced by COX-2
      expression.

PMID- 21853479
TI  - G quadruplexes stabilised by 8-oxo-2'-deoxyguanosine.

PMID- 21853480
TI  - 1,2-Dihydrotriazinyl-N-oxy free radicals.
AB  - Triazinyl-N-oxy free radicals, 2-methyl-2,4,6-triphenyl-1,2-dihydro-1,3,5
      triazinyl-1-oxy (6a), 2,2,4,6-tetraphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (6b),
      2,2-dimethyl-4,6-diphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (13), and 2,6
      dimethyl-2,4-diphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (14), in which the
      unpaired electron is delocalized over three nitrogen atoms, have been prepared
      and characterized. A method has been devised for introducing an N-oxide function
      into the triazinyl core. Then, by using a Grignard reagent, substitution alpha to
      the N-oxide group was achieved and the resulting 1,2-dihydrotriazine-N-oxide
      oxidized into the corresponding nitroxide. Solution EPR spectra exhibit hyperfine
      splitting that confirms spin delocalization over the three nitrogen atoms of the
      triazinyl ring. They also show that spin delocalization diminishes with
      increasing distance for the coupling and is largest for nitrogen N1 and weakest
      for N5. Free radicals 6a and 13 are stable in the solid state and have been
      characterized by X-ray diffraction, but they tend to gradually degrade in
      solution. In the solid state, these two free radicals are arranged into
      antiferromagnetically exchange-coupled pairs, J=-5.2(6) for 6a and -3.7(4) cm(-1)
      for 13 (H=-2JS(1)S(2)).

PMID- 21853481
TI  - Bifunctional N-acyl-aminophosphine-catalyzed asymmetric [4+2] cycloadditions of
      allenoates and imines.

PMID- 21853482
TI  - Synthesis of 3,7-disubstituted imipramines by palladium-catalysed
      amination/cyclisation and evaluation of their inhibition of monoamine
      transporters.
AB  - We describe a novel approach for the synthesis of a series of 3,7
      difunctionalised symmetric and unsymmetrical analogues of the tricyclic
      antidepressant (TCA) imipramine, which uses a key palladium-catalysed
      amination/cyclisation of an ester-functionalised dibromide. Of the ester, methyl,
      hydroxymethyl and methoxymethyl disubstituted compounds prepared, 3,7-dimethyl
      imipramine was found to be the most potent against the human serotonin
      transporter (hSERT). The inhibitory potency of 3,7-dimethyl imipramine was found
      to be at least as high as the parent imipramine. This novel TCA also exhibits an
      increased selectivity (relative to imipramine) in binding to hSERT versus the
      human norepinephrine transporter (hNET). Even higher selectivity could be
      obtained with 3,7-dihydroxymethyl imipramine, which was found to be 167-fold more
      selective for hSERT over hNET, representative of a 120-fold gain in selectivity
      relative to the parent imipramine. These results further validate our previous
      model for the binding of imipramine and high-affinity analogues of imipramine to
      the central binding site of hSERT.

PMID- 21853483
TI  - Rose bengal-grafted biodegradable microcapsules: singlet-oxygen generation and
      cancer-cell incapacitation.
AB  - Rose bengal-grafted chitosan (RB-CHI), synthesized through dehydration between
      amino and carboxyl functional groups under mild conditions, was coated onto the
      outer layer of preformed biodegradable microcapsules consisting of sodium
      alginate and chitosan. The fabricated photosensitive microcapsules were
      characterized by optical microscopy, scanning electron microscopy, and confocal
      laser scanning microscopy. The assembled materials maintained intact spherical
      morphology and thus showed good ability to form thin films. Electron spin
      resonance spectroscopy allowed direct observation of the generation of singlet
      oxygen ((1)O(2)) from photosensitive microcapsules under light excitation at
      about 545 nm. Furthermore, with increasing light radiation, the content of
      (1)O(2) increased, as detected by a chemical probe. In vitro cellular toxicity
      assays showed that RB-CHI-coated photosensitive microcapsules exhibit good
      biocompatibility in darkness and high cytotoxicity after irradiation, and could
      provide new photoresponsive drug-delivery vehicles.

PMID- 21853484
TI  - Isothiourea-catalysed asymmetric C-acylation of silyl ketene acetals.
AB  - Screening of a range of chiral isothioureas and acyl donors to promote the
      asymmetric C-acylation of silyl ketene acetals indicates that C(2)-aryl
      dihydropyrimidobenzothiazole-derived isothioureas and propionic anhydride give
      optimal reactivity and enantioselectivity in this process. Under optimised
      conditions 3-acyl-3-aryl or 3-acyl-3-alkylfuranones are prepared in good yields
      and moderate to excellent enantioselectivities (up to 98% ee; ee=enantiomeric
      excess).

PMID- 21853485
TI  - Bis(acetylacetonato)ruthenium complexes of noninnocent 1,2-dioxolene ligands:
      qualitatively different bonding in relation to monoimino and diimino analogues.
AB  - Coordination compounds [Ru(acac)(2)(Q)] (acac=acetylacetonate; Q=o-benzoquinone)
      were prepared as complexes 1 (Q=o-benzoquinone), 2 (Q=3-methoxy-o-benzoquinone),
      3 (Q=4-methyl-o-benzoquinone), and 4 (Q=3,5-di-tert-butyl-o-benzoquinone). The
      structures of 1 and 2 were determined to reveal a Ru(III)/o-benzosemiquinone
      formulation, supported by analysis of experimental data (spectroscopy, magnetism
      of 1) and by DFT calculations. The S=1 ground state calculated for 1 stands in
      contrast to the spin-paired analogues with arylimino-o-benzosemiquinonato and
      diimino-o-benzoquinone ligands. The close contacts of about 5.3 A possible
      between semiquinone O atoms of different molecules in the crystal allow for
      intermolecular spin-spin interactions and an overall complex magnetic behavior.
      One quasireversible oxidation and two reversible one-electron reductions yielded
      the corresponding molecular ions, which were characterized by UV-visible-NIR and
      EPR spectroelectrochemistry in terms of [Ru(III)(acac)(2)(Q(0))](+) ,
      [Ru(III)(acac)(2)(Q(2-))](-), and [Ru(II)(acac)(2)(Q(2-))](2-) descriptions in
      agreement with DFT results. The use of acceptor-substituted 1,2-dioxolenes
      resulted in the isolation of ionic species Na[Ru(acac)(2)(Q)] (Na(5); Q=4-chloro
      o-benzoquinone) and Na(6) (Q=4-nitro-o-benzoquinone), which were similarly
      investigated as compounds 1-4. Magnetic susceptibility and EPR results confirm an
      S=1/2 ground state based on ruthenium(III). The combined studies reveal a
      remarkable substituent sensitivity, and in comparison to recently analyzed
      Ru(acac)(2) complexes with o-benzoquinone monoimine and diimine ligands, the all
      O-donor-containing new systems are distinguished by a qualitatively different
      metal-ligand interaction based on closer intermolecular radical-radical contacts
      and on weaker intramolecular dpi-pi* interactions.

PMID- 21853486
TI  - Acid/base controllable molecular recognition.
AB  - The study of controllable molecular recognition in supramolecular receptors is
      important for elucidating design strategies that can lead to external control of
      molecular recognition applications. In this work, we present the design and
      synthesis of an asymmetric (TTF) tetrathiafulvalene-calix[4]pyrrole receptor and
      show that its recognition of 1,3,5-trinitrobenzene (TNB) can be controlled by an
      acid/base input. The new receptor is composed of three identical TTF units and a
      fourth TTF unit appended with a phenol moiety. Investigation of the host-guest
      complexation taking place between the TTF-calix[4]pyrrole receptor and the TNB
      guests was studied by means of absorption and (1)H NMR spectroscopy; this
      revealed that the conformation of the molecular receptor can be switched between
      locked and unlocked states by using base and acid as the input. In the unlocked
      state, the receptor is able to accommodate two TNB guest molecules, whereas the
      guests are not able to bind to the receptor in the locked state. This work serves
      to illustrate how external control (acid/base) of a receptor may be used to
      direct the molecular recognition of guests (TNBs). It has led to a new
      controllable molecular recognition system that functions as an acid/base switch.

PMID- 21853487
TI  - Two-dimensional nanocomposites based on chemically modified graphene.
AB  - The multiple functional groups and unique two-dimensional (2D) morphology make
      chemically modified graphene (CMG) an ideal template for the construction of 2D
      nanocomposites with various organic/inorganic components. Additionally, the
      recovered electrical conductivity of CMG may provide a fast-electron-transport
      channel and can thus promote the application of the resultant nanocomposites in
      optoelectronic and electrochemical devices. This Concept article summarizes the
      different strategies for the bottom-up fabrication of CMG-based 2D nanocomposites
      with small organic molecules, polymers, and inorganic nanoparticles, which
      represent the new directions in the development of graphene-based materials.

PMID- 21853488
TI  - Improved syntheses of phosphine ligands by direct coupling of
      diarylbromophosphine with organometallic reagents.

PMID- 21853489
TI  - How does Cu(II) convert into Cu(I)? An unexpected ring-mediated single-electron
      reduction.
AB  - Cu(x)O (x=1,2) nanomaterials with tailored composition and properties-a hot topic
      in sustainable technologies-may be fabricated from molecular sources through
      bottom-up processes that involve unexpected changes in the metal oxidation state
      and open intriguing challenges on the copper redox chemistry. How copper(II)
      sources may lead to copper(I) species in spite of the absence of any explicit
      reducing agent, and even in the presence of oxygen, is one such question-to date
      unanswered. Herein, we study copper "reduction without reductants" within one
      molecule and reveal that the actual reducing agent is abstracted atomic hydrogen.
      By investigating the fragmentation of a copper(II) precursor for copper oxide
      nanostructures by combined ESI-MS with multiple collisional experiments
      (ESI/MS(n)) and theoretical calculations, we highlight a copper-promoted C-H bond
      activation, leading to reduction of the metal center and formation of a Cu(I)-C
      NCCN six-membered ring. Such a novel ring system is the structural motif for a
      new family of cyclic copper(I) adducts, which show a bonding scheme, herein
      reported for the first time, that may shed unprecedented light on copper
      chemistry. Beyond the relevance for the preparation of copper oxide
      nanostructures, the hydrogen-abstraction/proton-delivery/electron-gain mechanism
      of copper(II) reduction disclosed herein appears to be a general property of
      copper and might help to understand its redox reactivity.

PMID- 21853490
TI  - A Janus [2]rotaxane synthesized by using an anion-templated clipping methodology.

PMID- 21853491
TI  - Unusual thermal decomposition of AgIISO4 Yielding AgI2S2O7: bending Hammond's
      rule.

PMID- 21853492
TI  - o-Alkoxyphenyliminoiodanes: highly efficient reagents for the catalytic
      aziridination of alkenes and the metal-free amination of organic substrates.

PMID- 21853493
TI  - Sodium relaxation times in the knee joint in vivo at 7T.
AB  - The sodium concentration correlates directly with the concentration of
      proteoglycans (PG) in cartilage, the loss of which is an early signature of
      osteoarthritis (OA). As a result, quantitative sodium MRI is a promising
      technique for assessing the degradation of articular cartilage in patients with
      OA. Sodium relaxation times can also provide information on the degradation of
      cartilage: it has already been shown on bovine cartilage that T(1) and T2long are
      longer and T2short shorter when the PG concentration decreases. In this study,
      sodium T(1), T2*short and T2*long relaxation maps were measured in vivo at 7 T on
      8 healthy volunteers and in 4 different regions of the cartilage in the knee
      joint. The patellar, femoro-tibial medial, lateral, and femoral condyle cartilage
      have an average T(1)~20 ms, but different T2*short (from 0.5 ms to 1.4 ms) and
      T2*long (from 11.4 ms to 14.8 ms). Statistically significant differences in T(1),
      T2*short and T2*long were observed between the different regions in cartilage (p
      << 10(- 5)). Statistical differences in T(1) were also observed between male and
      female data (p << 10(- 5)). These relaxation times measurements can further be
      applied as correction factors for sodium concentration maps in vivo and can also
      be useful as complementary information to quantitative sodium MRI in the quest
      for detecting early OA. These measurements were done on low resolution sodium
      images in order to acquire sufficient quality data for fitting (5 images for T(1)
      and 9 images for T2*) while keeping the total time of acquisition of the data
      reasonable for the volunteer's comfort (1 h 15 min).

PMID- 21853494
TI  - Separation of four homoisoflavonoids from Caesalpinia sappan by high-speed
      counter-current chromatography.
AB  - INTRODUCTION: The main chemical constituents of Caesalpinia sappan are
      homoisoflavonoids. Conventional column chromatographic techniques used for
      isolation of this type of compounds are tedious, time-consuming and waste
      solvents. High-speed counter-current chromatography (HSCCC) could be a suitable
      alternative for the enrichment and purification of these target compounds from
      traditional Chinese medicine (TCM). OBJECTIVE: To establish a method to isolate
      four homoisoflavonoids in one-step separation from C. sappan by HSCCC.
      METHODOLOGY: The crude extract of C. sappan was fractionated by HSCCC using a two
      phase solvent system consisting of chloroform-methanol-water (4:3:2, v/v/v). The
      separation conditions were: flow rate, 1.0 mL/min; revolution speed, 900 rpm;
      detection wavelength, 280 nm; separation temperature, 25  degrees C; sample size,
      120 mg crude sample dissolved in a mixture of the upper and lower phases (10 mL
      each). The retention of the stationary phase was 83%. RESULTS: Five milligrams of
      3'-deoxysappanol, 8 mg of 3-deoxysappanone B, 20 mg of 4-O-methylsappanol and 18
      mg of brazilin were obtained in one-step separation from 120 mg of an ethyl
      acetate extracted fraction of C. sappan. Their purities were 99%, 97%, 90% and
      85% by HPLC analysis. The mean recoveries of the four compounds were 83%, 86%,
      93% and 85%, respectively. CONCLUSION: The study has shown that HSCCC is
      effective for the separation and enrichment of the target compounds at a large
      scale.

PMID- 21853495
TI  - Quality evaluation of Desmodium styracifolium using high-performance liquid
      chromatography with photodiode array detection and electrospray ionisation tandem
      mass spectrometry.
AB  - INTRODUCTION: Desmodium styracifolium, with C-flavone glycosides as main
      pharmacological effective compounds, is a popular Chinese medicinal herb and has
      been used to treat urination disturbance, urolithiasis, edema and jaundice.
      However, few systematic methods have been reported on the quality control of this
      natural herb. OBJECTIVE: To develop a method for control the quality of D.
      styracifolium by combining chromatographic fingerprints and major constituent
      quantification. METHOD: Separations were performed on an Ultimate XB-C-18 column
      by gradient elution using acetonitrile and 0.1% aqueous formic acid. Analytes
      were identified by HPLC coupled with electrospray ionisation mass spectrometry
      experiments. RESULTS: Twenty common peaks in chromatographic fingerprints were
      first identified among 15 batches of D. styracifolium from various regions. On
      basis of this, a HPLC-PAD method was established to simultaneously quantify five
      major constituents, which was validated for limit of qualification, linearity and
      interday variation of precision and accuracy. CONCLUSION: The assay developed
      could be considered as a suitable quality control method of D. styracifolium.

PMID- 21853496
TI  - 1H-NMR simultaneous identification of health-relevant compounds in propolis
      extracts.
AB  - INTRODUCTION: Propolis is a resinous substance collected by bees from exudates of
      different plants that is rich in well-known health-relevant phenolic compounds
      such as flavonoids and phenolic acids. Propolis extracts are very complex
      matrices difficult to study. Different analytical methods are usable to analyse
      propolis extracts and to obtain chemical fingerprint but to our knowledge NMR has
      not previously been used for this purpose. OBJECTIVE: This study aims to
      demonstrate that it is possible to use 1H-NMR for the simultaneous recognition of
      phenolic compounds in complex matrices, such as propolis extracts, using
      appropriate tools for spectra pre-treatment and analysis. METHODOLOGY: In this
      work 12 typical phenolic propolis compounds (apigenin, chrysin, galangin,
      kaempferol, quercetin, naringenin, pinocembrin, pinostrobin, caffeic acid,
      cinnamic acid, p-coumaric acid and ferulic acid) were considered as reference
      compounds and their presence in samples was verified by HPLC-MS. A simple 1H-NMR
      sequence was used to obtain spectra of samples. Spectra were pre-treated by using
      an appropriate tool for spectra alignment and analysed by using software for the
      study of spectra originated from complex matrices. Sixty-five propolis samples
      were used to test the proposed identification procedure. RESULTS: Ten out of 12
      considered compounds were identified as statistically significant in most of the
      samples. CONCLUSION: This work suggests that it is possible to efficiently use 1H
      NMR, coupled with appropriate spectral analytical tools, for the simultaneous
      detection of phenolic compounds in complex matrices.

PMID- 21853497
TI  - Structure and stability of Gyuba, a beta-lactoglobulin chimera.
AB  - beta-lactoglobulin (LG) contains nine beta-strands (strands A-I) and one alpha
      helix. Strands A-H form a beta-barrel. At neutral pH, equine LG (ELG) is
      monomeric, whereas bovine LG (BLG) is dimeric, and the I-strands of its two
      subunits form an intermolecular beta-sheet. We previously constructed a chimeric
      ELG in which the sequence of the I-strand was replaced with that of BLG. This
      chimera did not dimerize. For this study, we constructed the new chimera we call
      Gyuba (which means cow and horse in Japanese). The amino acid sequence of Gyuba
      includes the sequences of the BLG secondary structures and those of the ELG
      loops. The crystal structure of Gyuba is very similar to that of BLG and
      indicates that Gyuba dimerizes via the intermolecular beta-sheet formed by the
      two I-strands. Thus, the entire arrangement of the secondary structural elements
      is important for LG dimer formation.

PMID- 21853498
TI  - Matched cohort analysis of the effect of pretreatment positron emission
      tomography on clinical outcomes of patients with head and neck cancer treated
      with definitive chemoradiotherapy.
AB  - BACKGROUND: Pretreatment positron emission tomography (PET) has been shown to be
      useful for patients with head and neck squamous cell carcinoma (HNSCC) after
      definitive chemoradiotherapy (CRT). METHODS: We conducted a retrospective
      analysis of a matched cohort of 116 patients with HNSCC that underwent CRT
      treatment at our institution. Pretreatment PET was performed in 58 patients and
      omitted in the other 58 patients. The 2 cohorts were matched for T
      classification, N classification, primary site, and smoking history. Kaplan-Meier
      2-year estimates of local control (LC), regional control (RC), freedom from
      distant metastasis (FFDM), cause-specific survival (CSS), and overall survival
      (OS) were compared with log-rank tests. RESULTS: There were no differences
      between the 2 cohorts for 2-year endpoints of LC, RC, FFDM, CSS, and OS. On
      multivariate analysis pretreatment PET imaging did not influence any endpoint.
      CONCLUSIONS: PET imaging before definitive CRT may not significantly improve
      outcomes in patients with HNSCC.

PMID- 21853499
TI  - Correlation of lymphatic vessel density and vascular endothelial growth factor
      with nodal metastasis in papillary thyroid microcarcinoma.
AB  - BACKGROUND: The aim of this study was to investigate not only the intratumoral
      and peritumoral lymphatic vessel density (ILD and PLD) but also the expression of
      vascular endothelial growth factors (VEGFs) and to test their correlation with
      regional lymph nodal metastases in papillary thyroid microcarcinoma (PTMC).
      METHODS: A clinicopathologic data review was performed in 60 patients with PTMC
      treated with total thyroidectomies involving neck dissections. The patterns of
      lymphatic vessels, the expression of VEGFs, and their correlation with neck
      metastases were assessed. RESULTS: PLD was significantly higher than ILD (p <
      .001). Patients with high PLD (>8.0) showed higher rates of neck metastases than
      low PLD (<= 8.0) (74.0% vs 46.8%, p = .03). Univariate and multivariate analyses
      revealed high PLD as the only independent variable predictive of neck metastasis.
      The expression of VEGFs did not correlate with either lymphatic density or neck
      metastasis. CONCLUSIONS: PLD may be of potential benefit in the prediction of
      neck metastasis in PTMC.

PMID- 21853500
TI  - Narrow band imaging endoscopy for unknown primary tumor sites of the neck.
AB  - BACKGROUND: Examinations used to search for unknown primary tumors of squamous
      cell carcinomas of the neck include CT, MRI, laryngoscopy, gastrointestinal
      endoscopy, and positron-emission tomography (PET). Narrow band imaging (NBI)
      endoscopy in which an optical color-separation filter is used to narrow the
      bandwidth of spectral transmittance is also used. METHODS: Twenty-eight patients
      in whom primary squamous cell carcinomas could not be detected with conventional
      white light laryngoscopy underwent NBI endoscopy and PET. RESULTS: Primary
      lesions were detected with NBI endoscopy in 3 patients, but no primary lesions
      were detected with PET. However, PET was used to detect a lower gingival cancer
      and a palatine tonsillar cancer. CONCLUSION: Both PET and NBI endoscopy is
      effective for detecting unknown primary tumors of squamous cell carcinomas of the
      neck.

PMID- 21853501
TI  - Osteosarcoma of the jaw in children and young adults.
AB  - BACKGROUND: Pediatric jaw osteosarcoma is uncommon, and data are scarce regarding
      clinical presentation, prognostic factors, and outcome. METHODS: A single
      institution medical record review from 1983 to 2008 for 12 patients age <= 21
      years was undertaken for this study. RESULTS: Median diagnosis age was 16.3 years
      (range, 6.3-21.9). Nine patients had mandible tumors. Osteoblastic subtype was
      most common (4 patients). Most tumors were large (ie, T2; n = 8) and high-grade
      (n = 8). Treatment characteristics were varied. Median follow-up was 27.1 months
      (range, 8-252 months). Five patients had tumor necrosis <80% after chemotherapy.
      No deaths were observed. CONCLUSION: Jaw osteosarcoma outcome is better compared
      to extremity osteosarcoma, but further study is required regarding clinical
      prognostic factors.

PMID- 21853502
TI  - Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate
      release.
AB  - Cannabis consumption results in impaired learning. The proper synchronization of
      neuronal activity in the mammalian hippocampus gives rise to network rhythms that
      are implicated in memory formation. Here, we have studied the impact of
      cannabinoids on hippocampal sharp waves and associated ripple oscillations using
      field- and whole-cell voltage-clamp recordings. We demonstrate that the
      activation of cannabinoid receptor 1 suppresses sharp wave-ripples (SWRs) in mice
      in vivo and in vitro. This suppression was paralleled by a selective reduction of
      SWR-associated inward but not outward charge transfer, demonstrating an
      impairment of excitation due to cannabinoid exposure. Adenosine, a presynaptic
      modulator of glutamate release, mimicked and occluded the observed consequences
      of cannabinoids on SWRs. We conclude that inhibition of glutamatergic feed
      forward excitation can explain cannabinoid-mediated disruption of SWRs and may
      account for cannabinoid-induced impairment of hippocampus-dependent memory.

PMID- 21853504
TI  - An MR comparison study of cardiogenic and noncardiogenic pulmonary edema in
      animal models.
AB  - PURPOSE: To apply magnetic resonance (MR) imaging to differential diagnosis of
      cardiogenic pulmonary edema (CPE) and noncardiogenic pulmonary edema (NCPE).
      MATERIALS AND METHODS: In the CPE group, MR measurements were performed on 5 rats
      just before and 3 h after administration of 21 +/- 2% body weight of normal
      saline. In the NCPE group, measurements were similarly performed on 5 animals
      just before and 48 h after 0.75 mg/body of lipopolysaccharide intratracheal
      administration. Animals were killed for bronchoalveolar lavage fluid (BALF) or
      pathological analysis after MR measurements. RESULTS: The relation between signal
      intensity and the T(2)* value of MR imaging was different in the two groups. The
      T(2)* in the NCPE group was significantly longer than that in the CPE group at
      the same signal intensity level. The lactate levels measured by in vivo MR
      spectroscopy did not show a difference between the CPE and NCPE groups, although
      the lactate BALF levels of the two groups were significantly different.
      CONCLUSION: The relation between signal intensity and T(2)* value was useful for
      the differentiation between these two pulmonary diseases. The measurable lactate
      level in pulmonary lesions suggests the applicability of MR spectroscopy to
      pulmonary disease.

PMID- 21853503
TI  - Differential effects of strain, circadian cycle, and stimulation pattern on LTP
      and concurrent LTD in the dentate gyrus of freely moving rats.
AB  - Because long-term potentiation (LTP) and long-term depression (LTD) are thought
      to be involved in learning and memory, it is important to delineate factors that
      modulate their induction and persistence, especially as studied in freely moving
      animals. Here, we investigated the effects of rat strain, circadian cycle, and
      high-frequency stimulation (HFS) pattern on LTP and concurrently induced LTD in
      the dentate gyrus (DG). Comparison of two commonly used rat strains revealed that
      medial perforant path field EPSP-population spike (E-S) coupling and LTP were
      greater in Long-Evans than Sprague-Dawley rats. Circadian cycle experiments
      conducted in Long-Evans rats revealed greater E-S coupling and enhanced LTP
      during the dark phase. Interestingly, concurrent LTD in the lateral perforant
      path did not significantly differ across strains or circadian cycle. Testing HFS
      protocols during the dark phase revealed that theta burst stimulation (100 Hz
      bursts at 5 Hz intervals) was ineffective in eliciting either LTP or concurrent
      LTD in DG, whereas 400 Hz bursts delivered at theta (5 Hz) or delta (1 Hz)
      frequencies produced substantial LTP and concurrent LTD. Thus, these natural and
      experimental factors regulate granule cell excitability, and differentially
      affect LTP and concurrent LTD in the DG of freely moving rats. (c) 2011 Wiley
      Periodicals, Inc.

PMID- 21853505
TI  - A comparison of two methods for estimating refill adherence to statins in Sweden:
      the RARE project.
AB  - PURPOSE: To analyse and compare refill adherence to statins estimated with two
      different methods with a focus on sensitivity to definitions. METHODS:
      Individuals aged 18-85 years who filled a statin prescription for the first time
      in 1.5 years during 1 January-30 June 2007 were followed until emigration or
      death or until 2 years after their first statin purchase. The data were collected
      via linkage between the Swedish Prescribed Drug Register, the National Patient
      Register and the Total Population Register. Days' supply was estimated based on
      amount dispensed and prescribed dosage. Refill adherence was estimated with the
      continuous measure of medication acquisition (CMA) and the maximum gap method
      (cut-off 45 days). The impact of altering definitions, for example, regarding
      hospitalisations, length of observation period and management of overlapping
      supply, was analysed. RESULTS: The study included 36, 661 individuals (mean age
      64 years, 47% women). The median proportion of days with statins was 95%, and 76%
      were classified as adherent with a cut-off at >= 80% with CMA. With the maximum
      gap method, 65% were adherent. Disregarding hospitalisations did not alter the
      results. Emigration or death at least one year after statin initiation was
      associated with a lower adherence with both methods, and a shorter observation
      period and adding overlapping supply to the subsequent prescription increased the
      adherence estimates. CONCLUSIONS: The choice of method and definitions,
      particularly regarding the management of overlapping supplies and the length of
      observation period, has a substantial impact on estimates of refill adherence to
      statins.

PMID- 21853506
TI  - Correlating disease-related mutations to their effect on protein stability: a
      large-scale analysis of the human proteome.
AB  - Single residue mutations in proteins are known to affect protein stability and
      function. As a consequence, they can be disease associated. Available
      computational methods starting from protein sequence/structure can predict
      whether a mutated residue is or not disease associated and whether it is
      promoting instability of the protein-folded structure. However, the relationship
      among stability changes in proteins and their involvement in human diseases still
      needs to be fully exploited. Here, we try to rationalize in a nutshell the
      complexity of the question by generalizing over information already stored in
      public databases. For each single aminoacid polymorphysm (SAP) type, we derive
      the probability of being disease-related (Pd) and compute from thermodynamic data
      three indexes indicating the probability of decreasing (P-), increasing (P+), and
      perturbing the protein structure stability (Pp). Statistically validated analysis
      of the different P/Pd correlations indicate that Pd best correlates with Pp.
      Pp/Pd correlation values are as high as 0.49, and increase up to 0.67 when data
      variability is taken into consideration. This is indicative of a medium/good
      correlation among Pd and Pp and corroborates the assumption that protein
      stability changes can also be disease associated at the proteome level.

PMID- 21853508
TI  - Bonding changes in plutonium(III) and americium(III) borates.

PMID- 21853509
TI  - Rotaxane-based mechanically linked block copolymers.

PMID- 21853510
TI  - Highly N2-selective palladium-catalyzed arylation of 1,2,3-triazoles.

PMID- 21853511
TI  - Investigations of the uptake of dimethylsulfoniopropionate by phytoplankton.
AB  - No change here: Analysis with doubly labeled [(13)C(2)D(6)]DMSP and LC/MS
      revealed that dissolved DMSP is taken up and stored intracellularly by diverse
      phytoplankton species without transformation. This is even true for species that
      produce no quantifiable amounts of DMSP themselves.

PMID- 21853512
TI  - A rapid assay for miRNA maturation by using unmodified pre-miRNA.
AB  - Without labeling RNA: A new rapid assay for micro-RNA maturation was developed.
      The assay depends on the cleavage of unmodified pre-miRNAs and the subsequent
      amplification of the mature miRNA by rolling circle amplification (see
      accompanying scheme).

PMID- 21853513
TI  - Electrochemical properties of oxidized carbon nano-onions: DRIFTS-FTIR and raman
      spectroscopic analyses.
AB  - The electrochemical reactions of carboxylic and lactone groups on carbon nano
      onions (CNOs) in aqueous solutions result in non-Kolbe products: alcohols,
      ketones, ethers and epoxides. The anodic/cathodic conversion of ox-CNOs was
      assessed by Boehm titrations and by Raman and DRIFTS-FTIR (diffuse reflectance
      infrared Fourier transform spectroscopy). The electrochemical properties of
      oxidized carbon nano-onions were investigated by cyclic voltammetry in aqueous
      solutions. The ox-CNOs are electrochemically active as a result of the reduction
      of the oxygen-containing groups.

PMID- 21853514
TI  - Phosphorescence energies of organic light-emitting diodes from spin-flip Tamm
      Dancoff approximation time-dependent density functional theory.
AB  - The phosphorescence energy in organometallic transition-metal compounds relevant
      for organic light-emitting diodes is calculated using spin-flip time-dependent
      density functional theory within the Tamm-Dancoff approximation, a technique
      presented by Wang and Ziegler. This method is implemented in the TURBOMOLE
      program suite by modifications of the present code. The predictions of the
      triplet-singlet transition energies with the spin-flip approach using functionals
      of the local density approximation are significantly more stable than those
      obtained from the indirect calculation as singlet-triplet excitation with
      conventional time-dependent density functional theory. They are also more stable
      than those of Delta-SCF, even if more sophisticated generalized gradient or
      hybrid functionals are used for the latter.

PMID- 21853515
TI  - In situ synchrotron radiation X-ray microspectroscopy of polymer microcontainers.
AB  - Direct, real-time analytical techniques that provide high-resolution information
      on the chemical composition and submicrometer structure of various polymer micro-
      and nanoparticles are in high demand in a range of life science disciplines.
      Synchrotron-based scanning transmission X-ray microspectroscopy (STXM) combines
      both local-spot chemical information (assessed via near-edge X-ray absorption
      fine structure spectroscopy) and imaging with resolution of several tens of
      nanometers, and thus can yield new insights into the nanoscale properties of
      these materials. Furthermore, this method allows in situ examination of soft
      matter samples in aqueous/gaseous environments and under external stimuli, such
      as temperature, pressure, ultrasound, and light irradiation. This Minireview
      highlights some recent progress in the application of the STXM technique to study
      the temperature-dependent behavior of polymer core-shell microcapsules and to
      characterize the physicochemical properties of the supporting shells of gas
      filled microbubbles in their natural hydrated state.

PMID- 21853516
TI  - Calorimetric study of propane and propylene adsorption on the active surface of
      multiwalled carbon nanotube catalysts.

PMID- 21853507
TI  - On the sequence-directed nature of human gene mutation: the role of genomic
      architecture and the local DNA sequence environment in mediating gene mutations
      underlying human inherited disease.
AB  - Different types of human gene mutation may vary in size, from structural variants
      (SVs) to single base-pair substitutions, but what they all have in common is that
      their nature, size and location are often determined either by specific
      characteristics of the local DNA sequence environment or by higher order features
      of the genomic architecture. The human genome is now recognized to contain
      "pervasive architectural flaws" in that certain DNA sequences are inherently
      mutation prone by virtue of their base composition, sequence repetitivity and/or
      epigenetic modification. Here, we explore how the nature, location and frequency
      of different types of mutation causing inherited disease are shaped in large
      part, and often in remarkably predictable ways, by the local DNA sequence
      environment. The mutability of a given gene or genomic region may also be
      influenced indirectly by a variety of noncanonical (non-B) secondary structures
      whose formation is facilitated by the underlying DNA sequence. Since these non-B
      DNA structures can interfere with subsequent DNA replication and repair and may
      serve to increase mutation frequencies in generalized fashion (i.e., both in the
      context of subtle mutations and SVs), they have the potential to serve as a
      unifying concept in studies of mutational mechanisms underlying human inherited
      disease.

PMID- 21853517
TI  - Theoretical study on cooperativity effects between anion-pi and halogen-bonding
      interactions.
AB  - This article analyzes the interplay between lone pair-pi (lp-pi) or anion-pi
      interactions and halogen-bonding interactions. Interesting cooperativity effects
      are observed when lp/anion-pi and halogen-bonding interactions coexist in the
      same complex, and they are found even in systems in which the distance between
      the anion and halogen-bond donor molecule is longer than 9 A. These effects are
      studied theoretically in terms of energetic and geometric features of the
      complexes, which are computed by ab initio methods. Bader's theory of "atoms in
      molecules" is used to characterize the interactions and to analyze their
      strengthening or weakening depending upon the variation of charge density at
      critical points. The physical nature of the interactions and cooperativity
      effects are studied by means of molecular interaction potential with polarization
      partition scheme. By taking advantage of all aforementioned computational
      methods, the present study examines how these interactions mutually influence
      each other. Additionally, experimental evidence for such interactions is obtained
      from the Cambridge Structural Database (CSD).

PMID- 21853519
TI  - Cardiac metastasis and hypertrophic osteoarthropathy in recurrent infantile
      fibrosarcoma.
AB  - Cardiac metastasis and hypertrophic osteoarthropathy are both quite rare. We
      describe a patient presenting with hypertrophic osteoarthropathy as the first
      symptom of recurrent infantile fibrosarcoma (IF). During surgical resection of
      lung metastasis, the patient suffered sudden cardiac arrest. Autopsy demonstrated
      a metastatic lesion in the intraventricular septum of the heart, which is
      previously undescribed in the literature. This case demonstrates that IF can be
      aggressive despite its more typical benign course.

PMID- 21853518
TI  - Determination of deferiprone in urine and serum using a terbium-sensitized
      luminescence method.
AB  - Optimized conditions, validation and practical applications of a new, rapid and
      specific fluorometric method for the determination of deferiprone (DFP) in urine
      and serum samples are reported. The proposed method, which is based on the
      formation of a luminescent complex with Tb(3+) ion, is evaluated in terms of
      linearity, accuracy, precision, stability, recovery and limits of detection (LOD)
      and quantification (LOQ). Under optimum conditions (pH 7.5, [Tb(3+)] = 3 * 10(-4)
      mol/L, temperature 0  degrees C and excitation wavelength 295 nm), the relative
      intensities at 545 nm are linear, with the concentration of DFP in the range
      0.072-13 mmol/L for urine and serum samples. The LOD and LOQ, respectively, are
      calculated to be 0.014 and 0.045 mmol/L for urine and 0.022 and 0.072 mmol/L for
      serum samples. The intra-day and inter-day values for the precision and accuracy
      of the proposed method are all < 5%, and the recovery of the method is in the
      range 97.1-103.8%. The method was applied to human urine and serum samples
      collected from patients receiving DFP. The results indicated that the method can
      be successfully applied to the determination of DFP in human urine and serum
      samples collected for clinical or biopharmaceutical investigations in which
      simple, rapid, cheap and specific determination methods facilitate and speed up
      the analytical procedure.

PMID- 21853520
TI  - Integrating Bayesian networks and geographic information systems: good practice
      examples.
AB  - Bayesian networks (BNs) are becoming increasingly common in problems with spatial
      aspects. The degree of spatial involvement may range from spatial mapping of BN
      outputs based on nodes in the BN that explicitly involve geographic features, to
      integration of different networks based on geographic information. In these
      situations, it is useful to consider how geographic information systems (GISs)
      could be used to enhance the conceptualization, quantification, and prediction of
      BNs. Here, we discuss some techniques that may be used to integrate GIS and BN
      models, with reference to some recent literature which illustrate these
      approaches. We then reflect on 2 case studies based on our own experience. The
      first involves the integration of GIS and a BN to assess the scientific factors
      associated with initiation of Lyngbya majuscula, a cyanobacterium that occurs in
      coastal waterways around the world. The 2nd case study involves the use of GISs
      as an aid for eliciting spatially informed expert opinion and expressing this
      information as prior distributions for a Bayesian model and as input into a BN.
      Elicitator, the prototype software package we developed for achieving this, is
      also briefly described. Whereas the 1st case study demonstrates a GIS-data driven
      specification of conditional probability tables for BNs with complete
      geographical coverage for all the data layers involved, the 2nd illustrates a
      situation in which we do not have complete coverage and we are forced to
      extrapolate based on expert judgement.

PMID- 21853521
TI  - Utility of population models to reduce uncertainty and increase value relevance
      in ecological risk assessments of pesticides: an example based on acute mortality
      data for daphnids.
AB  - Traditionally, ecological risk assessments (ERA) of pesticides have been based on
      risk ratios, where the predicted concentration of the chemical is compared to the
      concentration that causes biological effects. The concentration that causes
      biological effect is mostly determined from laboratory experiments using
      endpoints on the level of the individual (e.g., mortality and reproduction).
      However, the protection goals are mostly defined at the population level. To deal
      with the uncertainty in the necessary extrapolations, safety factors are used.
      Major disadvantages with this simplified approach is that it is difficult to
      relate a risk ratio to the environmental protection goals, and that the use of
      fixed safety factors can result in over- as well as underprotective assessments.
      To reduce uncertainty and increase value relevance in ERA, it has been argued
      that population models should be used more frequently. In the present study, we
      have used matrix population models for 3 daphnid species (Ceriodaphnia dubia,
      Daphnia magna, and D. pulex) to reduce uncertainty and increase value relevance
      in the ERA of a pesticide (spinosad). The survival rates in the models were
      reduced in accordance with data from traditional acute mortality tests. As no
      data on reproductive effects were available, the conservative assumption that no
      reproduction occurred during the exposure period was made. The models were used
      to calculate the minimum population size and the time to recovery. These
      endpoints can be related to the European Union (EU) protection goals for aquatic
      ecosystems in the vicinity of agricultural fields, which state that reversible
      population level effects are acceptable if there is recovery within an acceptable
      (undefined) time frame. The results of the population models were compared to the
      acceptable (according to EU documents) toxicity exposure ratio (TER) that was
      based on the same data. At the acceptable TER, which was based on the most
      sensitive species (C. dubia), the maximum reduction in population size was 13%
      and the maximum time to recovery was 4 d (both for D. magna). This information is
      clearly more informative for risk management than a risk ratio. For one of the
      species, D. pulex, a more complex model, which included sublethal effects on
      reproduction, was set up. The results of this model were in good agreement with a
      previous microcosm study and indicated that a traditional TER was overprotective.

PMID- 21853522
TI  - Rational application of chemicals in response to oil spills may reduce
      environmental damage.
AB  - Oil spills, for example those due to tanker collisions and groundings or platform
      accidents, can have huge adverse impacts on marine systems. The impact of an oil
      spill at sea depends on a number of factors, such as spill volume, type of oil
      spilled, weather conditions, and proximity to environmentally, economically, or
      socially sensitive areas. Oil spilled at sea threatens marine organisms, whole
      ecosystems, and economic resources in the immediate vicinity, such as fisheries,
      aquaculture, recreation, and tourism. Adequate response to any oil spill to
      minimize damage is therefore of great importance. The common response to an oil
      spill is to remove all visible oil from the water surface, either mechanically or
      by using chemicals to disperse the oil into the water column to biodegrade. This
      is not always the most suitable response to an oil spill, as the chemical
      application itself may also have adverse effects, or no response may be needed.
      In this article we discuss advantages and disadvantages of using chemical
      treatments to reduce the impact of an oil spill in relation to the conditions of
      the spill. The main characteristics of chemical treatment agents are discussed
      and presented within the context of a basic decision support scheme.

PMID- 21853523
TI  - Integrated Bayesian network framework for modeling complex ecological issues.
AB  - The management of environmental problems is multifaceted, requiring varied and
      sometimes conflicting objectives and perspectives to be considered. Bayesian
      network (BN) modeling facilitates the integration of information from diverse
      sources and is well suited to tackling the management challenges of complex
      environmental problems. However, combining several perspectives in one model can
      lead to large, unwieldy BNs that are difficult to maintain and understand.
      Conversely, an oversimplified model may lead to an unrealistic representation of
      the environmental problem. Environmental managers require the current research
      and available knowledge about an environmental problem of interest to be
      consolidated in a meaningful way, thereby enabling the assessment of potential
      impacts and different courses of action. Previous investigations of the
      environmental problem of interest may have already resulted in the construction
      of several disparate ecological models. On the other hand, the opportunity may
      exist to initiate this modeling. In the first instance, the challenge is to
      integrate existing models and to merge the information and perspectives from
      these models. In the second instance, the challenge is to include different
      aspects of the environmental problem incorporating both the scientific and
      management requirements. Although the paths leading to the combined model may
      differ for these 2 situations, the common objective is to design an integrated
      model that captures the available information and research, yet is simple to
      maintain, expand, and refine. BN modeling is typically an iterative process, and
      we describe a heuristic method, the iterative Bayesian network development cycle
      (IBNDC), for the development of integrated BN models that are suitable for both
      situations outlined above. The IBNDC approach facilitates object-oriented BN
      (OOBN) modeling, arguably viewed as the next logical step in adaptive management
      modeling, and that embraces iterative development. The benefits of OOBN modeling
      in the environmental community have not yet been fully realized in environmental
      management research. The IBNDC approach to BN modeling is described in the
      context of 2 case studies. The first is the initiation of blooms of Lyngbya
      majuscula, a blue-green algae, in Deception Bay, Australia where 3 existing
      models are being integrated, and the second case study is the viability of the
      free-ranging cheetah (Acinonyx jubatus) population in Namibia where an integrated
      OOBN model is created consisting of 3 independent subnetworks, each describing a
      particular aspect of free-ranging cheetah population conservation.

PMID- 21853526
TI  - State administrative data can aid long-term newborn follow-up, researchers
      report.

PMID- 21853527
TI  - A majority of parents accept newborn screening for fragile X.

PMID- 21853529
TI  - Patient acuity rating: quantifying clinical judgment regarding inpatient
      stability.
AB  - BACKGROUND: New resident work-hour restrictions are expected to result in further
      increases in the number of handoffs between inpatient care providers, a known
      risk factor for poor outcomes. Strategies for improving the accuracy and
      efficiency of provider sign-outs are needed. OBJECTIVE: To develop and test a
      judgment-based scale for conveying the risk of clinical deterioration. DESIGN:
      Prospective observational study. SETTING: University teaching hospital. SUBJECTS:
      Internal medicine clinicians and patients. MEASUREMENTS: The Patient Acuity
      Rating (PAR), a 7-point Likert score representing the likelihood of a patient
      experiencing a cardiac arrest or intensive care unit (ICU) transfer within the
      next 24 hours, was obtained from physicians and midlevel practitioners at the
      time of sign-out. Cross-covering physicians were blinded to the results, which
      were subsequently correlated with outcomes. RESULTS: Forty eligible clinicians
      consented to participate, providing 6034 individual scores on 3419 patient-days.
      Seventy-four patient-days resulted in cardiac arrest or ICU transfer within 24
      hours. The average PAR was 3 +/- 1 and yielded an area under the receiver
      operator characteristics curve (AUROC) of 0.82. Provider-specific AUROC values
      ranged from 0.69 for residents to 0.85 for attendings (P = 0.01). Interns and
      midlevels did not differ significantly from the other groups. A PAR of 4 or
      higher corresponded to a sensitivity of 82% and a specificity of 68% for
      predicting cardiac arrest or ICU transfer in the next 24 hours. CONCLUSIONS:
      Clinical judgment regarding patient stability can be reliably quantified in a
      simple score with the potential for efficiently conveying complex assessments of
      at-risk patients during handoffs between healthcare members.

PMID- 21853530
TI  - Human lung stem cells: oh, the places you'll go!

PMID- 21853531
TI  - Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related
      orphan receptor gamma.
AB  - Obesity is a well-known risk factor for the development of secondary
      complications such as type 2 diabetes. However, only a part of the obese
      population develops secondary metabolic disorders. Here, we identify the
      transcription factor retinoid-related orphan receptor gamma (RORgamma) as a
      negative regulator of adipocyte differentiation through expression of its newly
      identified target gene matrix metalloproteinase 3. In vivo differentiation of
      adipocyte progenitor cells from Rorgamma-deficient mice is enhanced and obese
      Rorgamma(-/-)  mice show decreased adipocyte sizes. These small adipocytes are
      highly insulin sensitive, leading to an improved control of circulating free
      fatty acids. Ultimately, Rorgamma(-/-)  mice are protected from hyperglycemia and
      insulin resistance in the state of obesity. In adipose stromal-vascular fraction
      from obese human subjects, Rorgamma expression is correlated with adipocyte size
      and negatively correlated with adipogenesis and insulin sensitivity. Taken
      together, our findings identify RORgamma as a factor, which controls adipogenesis
      as well as adipocyte size and modulates insulin sensitivity in obesity. RORgamma
      might therefore serve as a novel pharmaceutical target to treat obesity
      associated insulin resistance.

PMID- 21853532
TI  - Finding aptamers and small ribozymes in unexpected places.
AB  - The discovery of the catalytic properties of RNAs was a milestone for our view of
      how life emerged and forced us to reformulate many of our dogmas. The urge to
      grasp the whole spectrum of potential activities of RNA molecules stimulated two
      decades of fervent research resulting in a deep understanding of RNA-based
      phenomena. Most ribozymes were discovered by serendipity during the analysis of
      chemical processes, whereas RNA aptamers were identified through meticulous
      design and selection even before their discovery in nature. The desire to obtain
      aptamers led to the development of sophisticated technology and the design of
      efficient strategies. With the new notion that transcriptomes cover a major part
      of genomes and determine the identity of cells, it is reasonable to speculate
      that many more aptamers and ribozymes are awaiting their discovery in unexpected
      places. Now, in the genomic era with the development of powerful bioinformatics
      and sequencing methods, we are overwhelmed with tools for studying the genomes of
      all living and possibly even extinct organisms. Genomic SELEX (systematic
      evolution of ligands by exponential enrichment) coupled with deep sequencing and
      sophisticated computational analysis not only gives access to unexplored parts of
      sequenced genomes but also allows screening metagenomes in an unbiased manner.

PMID- 21853534
TI  - Reactions of ruthenium-allenylidene complexes tethering a cyclopropyl group.
AB  - Two cyclopropyl allenylidene complexes [Ru]=C=C=C(R)(C(3)H(5))
      ([Ru]=[RuCp(PPh(3))(2)], Cp=Cyclopentadienyl; R=thiophene (2a) and R=Ph (2b)) are
      prepared from the reactions of [Ru]Cl with the corresponding 1-cyclopropyl-2
      propyn-1-ol in the presence of KPF(6). Thermal treatment, halide-anion addition,
      and palladium-catalyzed reactions of 2a and 2b all lead to a ring expansion of
      the cyclopropyl group, giving the vinylidene complexes 4a and 4b, respectively,
      each with a five-membered ring. This ring expansion proceeds by C-C bond
      formation between Cbeta of the cumulative double bond and a methylene group of
      the cyclopropyl ring. In the reaction of 2a with pyrrole, consecutive formation
      of two C-C bonds, one between C-2 of pyrrole and Cgamma of 2a and the other
      between C-3 of pyrrole and Calpha, results in the formation of 6a. The reaction
      proceeds by addition of pyrrole and 1,3-proton shifts. The hydrogenation of 2a by
      NaBH(4) is carried out in different solvents. The cumulative double bonds are
      reduced regioselectively to give a mixture of 7a and 8a. Interestingly, use of
      different solvents leads to different ratios of 7a and 8a. Presence of a protic
      solvent like methanol in dichloromethane or chloroform solution increases the
      yield of 8a, thus revealing that both the rates of hydroboration and deboronation
      increase. The structures of two new complexes 4a and 6a have been firmly
      established by X-ray diffraction analysis.

PMID- 21853533
TI  - 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic
      transcription.
AB  - The human 7SK small nuclear RNA (snRNA) is an abundant noncoding RNA whose
      function has been conserved in evolution from invertebrates to humans. It is
      transcribed by RNA polymerase III (RNAPIII) and is located in the nucleus.
      Together with associated cellular proteins, 7SK snRNA regulates the activity of
      the positive transcription elongation factor b (P-TEFb). In humans, this
      regulation is accomplished by the recruitment of P-TEFb by the 7SK snRNA-binding
      proteins, hexamethylene bisacetamide (HMBA)-induced mRNA 1/2 (HEXIM1 or HEXIM2),
      which inhibit the kinase activity of P-TEFb. P-TEFb regulates the transition of
      promoter proximally paused RNA polymerase II (RNAPII) into productive elongation,
      thereby, allowing efficient mRNA production. The protein composition of the 7SK
      small nuclear ribonucleoprotein (snRNP) is regulated dynamically. While the Lupus
      antigen (La)-related protein 7 (LARP7) is a constitutive component, the
      methylphosphate capping enzyme (MePCE) associates secondarily to phosphorylate
      the 5' end of 7SK snRNA. The release of active P-TEFb is closely followed by
      release of HEXIM proteins and both are replaced by heterogeneous nuclear
      ribonucleoproteins (hnRNPs). The released P-TEFb activates the expression of most
      cellular and viral genes. Regulated release of P-TEFb determines the expression
      pattern of many of the genes that respond to environmental stimuli and regulate
      growth, proliferation, and differentiation of cells.

PMID- 21853535
TI  - Efficient synthetic protocols in glycerol under heterogeneous catalysis.
AB  - The massive increase in glycerol production from the transesterification of
      vegetable oils has stimulated a large effort to find novel uses for this
      compound. Hence, the use of glycerol as a solvent for organic synthesis has drawn
      particular interest. Drawbacks of this green and renewable solvent are a low
      solubility of highly hydrophobic molecules and a high viscosity, which often
      requires the use of a fluidifying co-solvent. These limitations can be easily
      overcome by performing reactions under high-intensity ultrasound and microwaves
      in a stand-alone or combined manner. These non-conventional techniques facilitate
      and widen the use of glycerol as a solvent in organic synthesis. Glycerol allows
      excellent acoustic cavitation even at high temperatures (70-100  degrees C),
      which is otherwise negligible in water. Herein, we describe three different types
      of applications: 1) the catalytic transfer hydrogenation of benzaldehyde to
      benzyl alcohol in which glycerol plays the dual role of the solvent and hydrogen
      donor; 2) the palladium-catalyzed Suzuki cross-coupling; and (3) the Barbier
      reaction. In all cases glycerol proved to be a greener, less expensive, and safer
      alternative to the classic volatile organic solvents.

PMID- 21853536
TI  - An inorganic iodine-catalyzed oxidative system for the synthesis of
      benzimidazoles using hydrogen peroxide under ambient conditions.

PMID- 21853537
TI  - Integrative physical oncology.
AB  - Cancer is arguably the ultimate complex biological system. Solid tumors are
      microstructured soft matter that evolves as a consequence of spatio-temporal
      events at the intracellular (e.g., signaling pathways, macromolecular
      trafficking), intercellular (e.g., cell-cell adhesion/communication), and tissue
      (e.g., cell-extracellular matrix interactions, mechanical forces) scales. To gain
      insight, tumor and developmental biologists have gathered a wealth of molecular,
      cellular, and genetic data, including immunohistochemical measurements of cell
      type-specific division and death rates, lineage tracing, and gain-of
      function/loss-of-function mutational analyses. These data are empirically
      extrapolated to a diagnosis/prognosis of tissue-scale behavior, e.g., for
      clinical decision. Integrative physical oncology (IPO) is the science that
      develops physically consistent mathematical approaches to address the significant
      challenge of bridging the nano (nm)-micro (um) to macro (mm, cm) scales with
      respect to tumor development and progression. In the current literature, such
      approaches are referred to as multiscale modeling. In the present article, we
      attempt to assess recent modeling approaches on each separate scale and
      critically evaluate the current 'hybrid-multiscale' models used to investigate
      tumor growth in the context of brain and breast cancers. Finally, we provide our
      perspective on the further development and the impact of IPO.

PMID- 21853539
TI  - Impact of environmental factors on marijuana use in 11 European countries.
AB  - AIM: To investigate the association between environmental factors (perceived
      availability of marijuana, perceived use among friends and siblings, use of
      alcohol and tobacco, family structure, parental control, school performance) and
      lifetime prevalence and frequent and early marijuana use in high school students.
      METHODS: We used self-reported data from 15-16 years old participants of the 2003
      European School Survey Project on Alcohol and Other Drugs (ESPAD) conducted in 11
      countries: Denmark, Estonia, Norway, Croatia, Slovenia, Germany, Switzerland,
      Bulgaria, Czech Republic, Russian Federation, and Ukraine. Multivariate logistic
      regression was used for data analysis. RESULTS: Countries varied according to
      lifetime prevalence (8.7%-47.8%) and frequent (8.7%-23.9%) and early (3.0%-13.0%)
      marijuana use. Daily tobacco smoking was most strongly associated with lifetime
      marijuana use for boys in 7 and for girls in 5 countries, with highest odds ratio
      (OR, 95% and confidence interval - CI) for boys in Denmark (OR, 13.52; 95% CI,
      8.16-22.4), and for girls in the Czech Republic (OR, 21.21; 95% CI, 12.99-34.62).
      Perceived marijuana availability was most strongly associated with frequent
      marijuana use for boys in 4 countries (highest in Slovenia: OR, 19.28; 95% CI,
      6.52-57.02) and girls in 5 (highest in Slovenia: OR, 19.05; 95% CI, 5.18-70.04).
      Perceived use of marijuana among friends was most strongly associated with
      frequent marijuana use in 5 countries, both for boys (highest in Norway: OR,
      23.91; 95% CI, 4.16-137.48) and girls (highest in Denmark: OR, 75.42; 95% CI,
      13.11-433.90). Perceived use of marijuana among friends was most strongly
      associated with early marijuana use in 8 countries for boys (highest in Norway:
      OR, 54.03; 95% CI, 3.34-875.19) and 3 countries for girls (highest in Denmark:
      OR, 7.29; 95%CI, 1.77-30.12). CONCLUSION: In each country, marijuana use was
      associated with similar factors, regardless of marijuana use prevalence in that
      country.The influence of peer group and perceived availability of marijuana
      seemed more important than parental control and family structure.

PMID- 21853540
TI  - Changes in human immunodeficiency virus and sexually transmitted infections
      related sexual risk taking among young Croatian adults: 2005 and 2010 population
      based surveys.
AB  - AIM: To determine changes in sexual behaviors and other relevant characteristics
      related to human immunodeficiency virus (HIV) and sexually transmitted infection
      (STI) risks among young Croatian adults. METHOD: We surveyed adults aged 18-24 in
      2005 (n=1092) and 18-25 in 2010 (n=1005). Both samples were probabilistic and
      stratified by county, settlement size, age, and gender. The samples were non
      matched. Trained interviewers conducted structured face-to-face interviews in
      participants' households. The part of the questionnaire assessing sensitive
      information was self-administered. RESULTS: A majority of participants at both
      survey points (85.2%-86.2%) were sexually active. Median age at sexual debut (17
      years) remained unchanged. Lifetime number of sexual partners was also stable.
      More women than men reported only one lifetime sexual partner. The prevalence of
      condom use at first intercourse increased (from 62.6 to 70%, P=0.002), while the
      prevalence of condom use at most recent sexual intercourse remained stable (54%
      in 2005 and 54.7% in 2010). Consistent condom use also remained unchanged.
      Consistent condom use in the past year was reported by 19.2% participants in 2005
      nad 20% in 2010.. At both survey points for both genders, consistent condom use
      was associated with age (odds ratio [OR] W2005=0.74, P=0.004; ORW2010=0.72,
      P<0.001; ORM2005=0.73, P<0.001; ORM2010=0.80,P=0.006), negative attitudes toward
      condom use (ORW2005=0.84, P=0.001; ORW2010=0.90, P=0.026; ORM2005=0.92, P=0.032;
      ORM2010=0.90, P=0.011)), and condom use at first intercourse (ORW2005=3.87,
      P<0.001; ORW2010=4.64, P<0.001; ORM2005=5.85, P<0.001; ORM2010=4.03, P<0.001). In
      the observed period, HIV/AIDS knowledge was stable. CONCLUSION: Risky sexual
      practices remain common among young Croatian adults. Given the recently reported
      STI prevalence rates in this age cohort, introduction of school-based sex
      education that would focus on protective behavioral and communication skills
      seems to be of crucial epidemiological importance.

PMID- 21853541
TI  - Sex differences in patterns of relations between family interactions and
      depressive symptoms in adolescents.
AB  - AIM: To gain insight into the relations between protective/risk family
      interactions and depressive symptoms in adolescent boys and girls. METHOD: A self
      reported cross-sectional survey was conducted on a representative sample of 1191
      secondary school students (617 girls and 574 boys) aged from 14 to 19 years, with
      a median of 16, from all secondary schools in the Primorsko-goranska County,
      Croatia in January and February 2010. Students reported their depressive
      symptoms, perceptions about the relationship with their mother and father, family
      activities, and parents' conflict resolution strategies. Data were analyzed by
      hierarchical multiple regression to calculate the effects of family supportive
      and harmful interactions on depressive symptoms in girls and boys. RESULTS:
      Depressive symptoms were reported often and very often by 19.1% of girls and
      15.8% of boys. Girls' assessment of the family relations was significantly more
      positive than boys', including the assessment of family activities, constructive
      family conflict resolution, or father's and mother's warmth and affection.
      Multiple correlation analysis revealed that the examined family variables
      accounted for 16.3% of the variance of depressive symptoms in boys and for 17.2%
      in girls. Hierarchical multiple regression analysis showed a difference in the
      relation of family variables and depressive symptoms between boys and girls.
      Depressive symptoms in girls were more linked to the lack of protective family
      factors (9.9% of the explained variance in girls vs. 5.5% in boys), while
      depressive symptoms in boys were more linked to the existence of harmful family
      factors (10.8% of the explained variance in boys vs.7.3% in girls). CONCLUSION:
      Family activities and the father's warmth and affection have a higher
      significance for girls than for boys, while destructive parental conflict and the
      mother's aggression and hostility are equally significant for both girls and
      boys. These results indicate the targets for family-based preventive and
      intervention programs for depression in adolescents.

PMID- 21853542
TI  - Cancer epidemiology in Central, South and Eastern European countries.
AB  - AIM: To collect cancer epidemiology data in South Eastern European countries as a
      basis for potential comparison of their performance in cancer care. METHODS: The
      South Eastern European Research Oncology Group (SEEROG) collected and analyzed
      epidemiological data on incidence and mortality that reflect cancer management in
      8 countries - Croatia, Czech Republic, Hungary, Romania, Poland, Slovakia, and
      Serbia and Montenegro in the last 20-40 years. RESULTS: The most common cancer
      type in men in all countries was lung cancer, followed by colorectal and prostate
      cancer, with the exception of the Czech Republic, where prostate cancer and
      colorectal cancer were more common. The most frequent cancer in women was breast
      cancer followed by colorectal cancer, with the exceptions of Romania and Central
      Serbia where cervical cancer was the second most common. Cancer mortality data
      from the last 20-40 years revealed two different patterns in men. In Romania and
      in Serbia and Montenegro, there was a trend toward an increase, while in the
      other countries mortality was declining, after increasing for a number of years.
      In women, a steady decline was observed over many years in the Czech Republic,
      Hungary, and Slovakia, while in the other countries it remained unchanged.
      CONCLUSIONS: There are striking variations in the risk of different cancers by
      geographic area. Most of the international variation is due to exposure to known
      or suspected risk factors which provides a clear challenge to prevention. There
      are some differences in incidence and mortality that cannot be explained by
      exposure to known risk factors or treatment availabilities.

PMID- 21853543
TI  - Clinical sensitivity and specificity of multiple T2-hyperintensities on brain
      magnetic resonance imaging in diagnosis of neurofibromatosis type 1 in children:
      diagnostic accuracy study.
AB  - AIM: To determine the prevalence, number, and location of multiple (>=2) T2
      hyperintensities on brain magnetic resonance imaging (MRI) in children with
      neurofibromatosis type 1 (NF1) and their correlation with age, and to establish
      their sensitivity, specificity, and accuracy for the diagnosis of NF1 in
      children, especially in the early age (2-7 years). METHODS: We performed a cross
      sectional study of 162 patients with NF1 from Croatian Neurofibromatosis
      Association Database and 163 control children between the ages of 2 and 18 years
      who underwent brain MRI between 1989 and 2009. RESULTS: Multiple T2
      hyperintensities were present in 74% of NF1 patients and 1.8% of controls. They
      were mainly located in the basal ganglia, brainstem, and cerebellum and were
      significantly decreased in prevalence and number in the older age. T2
      hyperintensities had excellent diagnostic accuracy with the area under the
      receiver operating characteristic (ROC) curve of 0.849 and 95% confidence
      interval (CI) of 0.805-0.886. The diagnostic sensitivity, specificity, and
      accuracy rate of T2-hyperintensities for NF1 were highest in the youngest age (2
      7 years): 81% (95% CI 71%-89.1%), 99% (95% CI 92.3%-100%), and 85.8 (95% CI 83.3
      93.8), respectively. CONCLUSION: This study strongly suggests the inclusion of T2
      hyperintensities on brain MRI on the list of diagnostic criteria for NF1,
      especially in children of early age, when the clinical penetration of the NF1
      gene has not yet been completely finished.

PMID- 21853544
TI  - Stapled hemorrhoidopexy, an innovative surgical procedure for hemorrhoidal
      prolapse: cost-utility analysis.
AB  - AIM: To undertake full economic evaluation of stapled hemorrhoidopexy (PPH) to
      establish its cost-effectiveness and investigate whether PPH can become cost
      saving compared to conventional excisional hemorrhoidectomy (CH). METHODS: A cost
      utility analysis in hospital and health care system (UK) was undertaken using a
      probabilistic, cohort-based decision tree to compare the use of PPH with CH.
      Sensitivity analyses allowed showing outcomes in regard to the variations in
      clinical practice of PPH procedure. The participants were patients undergoing
      initial surgical treatment of third and fourth degree hemorrhoids within a 1-year
      time-horizon. Data on clinical effectiveness were obtained from a systematic
      review of the literature. Main outcome measures were the cost per procedure at
      the hospital level, total direct costs from the health care system perspective,
      quality adjusted life years (QALY) gained and incremental cost per QALY gained.
      RESULTS: A decrease in operating theater time and hospital stay associated with
      PPH led to a cost saving compared to CH of GBP 27 (US $43.11, ?30.50) per
      procedure at the hospital level and to an incremental cost of GBP 33 (US $52.68,
      ?37.29) after one year from the societal perspective. Calculation of QALYs
      induced an incremental QALY of 0.0076 and showed an incremental cost-effective
      ratio (ICER) of GBP 4316 (US $6890.47, ?4878.37). Taking into consideration
      recent literature on clinical outcomes, PPH becomes cost saving compared to CH
      for the health care system. CONCLUSIONS: PPH is a cost-effective procedure with
      an ICER of GBP 4136 and it seems that an innovative surgical procedure could be
      cost saving in routine clinical practice.

PMID- 21853545
TI  - Disorder of extreme stress not otherwise specified (DESNOS) in Croatian war
      veterans with posttraumatic stress disorder: case-control study.
AB  - AIM: To determine the presence of disorder of extreme stress not otherwise
      specified (DESNOS) in Croatian war veterans who suffer from combat-related
      posttraumatic stress disorder (PTSD). METHODS: The research included 247 veterans
      of the 1991-1995 war in Croatia who suffered from PTSD and were psychiatrically
      examined at four clinical centers in Croatia during a month in 2008. It was based
      on the following self-assessment instruments: The Harvard Trauma Questionnaire
      (HTQ): Croatian Version, the Structured Interview for Disorder of Extreme Stress
      (SIDES-SR), and the Mini International Neuropsychiatric Interview (MINI).
      RESULTS: Based on the SIDES-SR results, we formed two groups of participants: the
      group with PTSD (N=140) and the group with both PTSD and DESNOS (N=107). Forty
      three percent of participants met the criteria for DESNOS. There was a
      significant difference in the intensity of posttraumatic symptoms between the
      group with both PTSD and DESNOS and the group with PTSD only (U=3733.5, P=0.001).
      Respondents who suffered from both PTSD and DESNOS also reported a significantly
      larger number of comorbid mental disorders (U=1123.5, P=0.049) and twice more
      frequently reported comorbid depression with melancholic features (OR=2.109,
      P=0.043), social phobia (OR=2.137, P=0.036), or panic disorder (OR=2.208,
      P=0.015). CONCLUSION: Our results demonstrate that PTSD and DESNOS can occur in
      comorbidity, which is in contrast with the ICD-10 criteria. A greater intensity
      of symptoms and a more frequent comorbidity with other psychiatric disorders,
      especially depression, panic disorder, and social phobia require additional
      therapy interventions in the treatment processes.

PMID- 21853546
TI  - Clinical laboratory as an economic model for business performance analysis.
AB  - AIM: To perform SWOT (strengths, weaknesses, opportunities, and threats) analysis
      of a clinical laboratory as an economic model that may be used to improve
      business performance of laboratories by removing weaknesses, minimizing threats,
      and using external opportunities and internal strengths. METHODS: Impact of
      possible threats to and weaknesses of the Clinical Laboratory at Nasice General
      County Hospital business performance and use of strengths and opportunities to
      improve operating profit were simulated using models created on the basis of SWOT
      analysis results. The operating profit as a measure of profitability of the
      clinical laboratory was defined as total revenue minus total expenses and
      presented using a profit and loss account. Changes in the input parameters in the
      profit and loss account for 2008 were determined using opportunities and
      potential threats, and economic sensitivity analysis was made by using changes in
      the key parameters. The profit and loss account and economic sensitivity analysis
      were tools for quantifying the impact of changes in the revenues and expenses on
      the business operations of clinical laboratory. RESULTS: Results of simulation
      models showed that operational profit of ?470 723 in 2008 could be reduced to
      only ?21 542 if all possible threats became a reality and current weaknesses
      remained the same. Also, operational gain could be increased to ?535 804 if
      laboratory strengths and opportunities were utilized. If both the opportunities
      and threats became a reality, the operational profit would decrease by ?384 465.
      CONCLUSION: The operational profit of the clinical laboratory could be
      significantly reduced if all threats became a reality and the current weaknesses
      remained the same. The operational profit could be increased by utilizing
      strengths and opportunities as much as possible. This type of modeling may be
      used to monitor business operations of any clinical laboratory and improve its
      financial situation by implementing changes in the next fiscal period.

PMID- 21853547
TI  - Application of the procedural consolidation concept to surgical treatment of
      children with epidermolysis bullosa: a retrospective analysis.
AB  - AIM: To assess the efficacy of the procedural consolidation concept (PCC) at
      reducing the number of sessions of general anesthesia necessary for treating
      children with epidermolysis bullosa (EB). METHODS: We examined the records of
      children treated at Children's Hospital of Zagreb between April 1999 and December
      2007. Children treated before the introduction of PCC in January 2005 (n=39) and
      after (n=48) were analyzed in order to determine the effect of PCC on the
      occurrence of complications, days of hospitalization, and number of
      hospitalizations. RESULTS: During the study period, 53 patients underwent 220
      sessions of general anesthesia for a total of 743 surgical interventions per
      session. Before the introduction of PCC (n=39 patients, 83 sessions), the median
      number of interventions per session was 2 (range 1-5), and after the introduction
      of PCC (n=48 patients, 137 sessions) it was 4 (range 3-7, P<0.001). After the
      introduction of PCC, the median number of complications per anesthesia session
      increased from 2 (range 0-10) to 3 (range 0-10) (P=0.027), but the median number
      of complications per surgical procedure decreased from 1 (range 0-10) to 0.6
      (range 0-2.5) (P<0.001). PCC lengthened each anesthesia session from a median of
      65 minutes (range 35-655) to 95 minutes (range 50-405), (P<0.001). Total length
      of hospitalization was similar before (median 1, range 1-4) and after (median 1,
      range 1-3) introduction of PCC (P=0.169). The number of hospitalization days per
      procedure was 3 times lower after the introduction of PCC (median 0.3, range 0.2
      3) than before (median 1, range 0.75-1.7) (P<0.001). CONCLUSION: PCC should be
      considered an option in the surgical treatment of children with EB.

PMID- 21853548
TI  - Morning-evening type and burnout level as factors influencing sleep quality of
      shift nurses: a questionnaire study.
AB  - AIM: To assess the relationship between sleep quality and demographic variables,
      morning-evening type, and burnout in nurses who work shift. METHODS: We carried
      out a cross-sectional self-administered study with forced choice and open-ended
      structured questionnaires - Pittsburgh Sleep Quality Index, Morningness
      eveningness Questionnaire, and Maslach Burnout Inventory. The study was carried
      out at Gazi University Medicine Faculty Hospital of Ankara on 524 invited nurses
      from July to September 2008, with a response rate of 89.94% (n=483). Descriptive
      and inferential statistics were applied to determine the risk factors of poor
      sleep quality. RESULTS: Most socio-demographic variables did not affect sleep
      quality. Participants with poor sleep quality had quite high burnout levels. Most
      nurses who belonged to a type that is neither morning nor evening had poor sleep
      quality. Nurses who experienced an incident worsening their sleep patterns
      (P<0.001) and needlestick or sharp object injuries (P=0.010) in the last month
      had poor sleep quality. The subjective sleep quality and sleep latency points of
      evening types within created models for the effect of burnout dimensions were
      high. CONCLUSIONS: Nurses working consistently either in the morning or at night
      had better sleep quality than those working rotating shifts. Further studies are
      still needed to develop interventions that improve sleep quality and decrease
      burnout in nurses working shifts.

PMID- 21853549
TI  - Personality, organizational stress, and attitudes toward work as prospective
      predictors of professional burnout in hospital nurses.
AB  - AIM: To examine to what extent personality traits (extraversion, agreeableness,
      conscientiousness, neuroticism, and openness), organizational stress, and
      attitudes toward work and interactions between personality and either
      organizational stress or attitudes toward work prospectively predict 3 components
      of burnout. METHODS: The study was carried out on 118 hospital nurses. Data were
      analyzed by a set of hierarchical regression analyses, in which personality
      traits, measures of organizational stress, and attitudes toward work, as well as
      interactions between personality and either organizational stress or attitudes
      toward work were included as predictors, while 3 indices of burnout were measured
      4 years later as criteria variables. RESULTS: Personality traits proved to be
      significant but weak prospective predictors of burnout and as a group predicted
      only reduced professional efficacy (R(2)=0.10), with agreeableness being a single
      negative predictor. Organizational stress was positive, affective-normative
      commitment negative predictor, while continuance commitment was not related to
      any dimension of burnout. We found interactions between neuroticism as well as
      conscientiousness and organizational stress, measured as role conflict and work
      overload, on reduced professional efficacy (betaNRCWO=-0.30; betacRCWO=-0.26). We
      also found interactions between neuroticism and affective normative commitment
      (beta=0.24) and between openness and continuance commitment on reduced
      professional efficacy (beta=-0.23), as well as interactions between
      conscientiousness and continuance commitment on exhaustion. CONCLUSION: Although
      contextual variables were strong prospective predictors and personality traits
      weak predictors of burnout, the results suggested the importance of the
      interaction between personality and contextual variables in predicting burnout.

PMID- 21853550
TI  - Health-related quality of life of women with disabilities in relation to their
      employment status.
AB  - AIM: To compare the health-related quality of life of unemployed and employed
      women with disabilities and establish factors affecting their life satisfaction.
      METHODS: The study included 318 women with disabilities, 160 of whom were
      employed and 158 unemployed, paired according to age and region of residence. The
      health-related quality of life was assessed by The World Health Organization
      Quality of Life questionnaire, and social demographics and factors affecting life
      satisfaction were collected by a general questionnaire. The factors affecting
      life satisfaction were defined according to respondents' statements. RESULTS:
      Unemployed women with disabilities had a lower mean score (+/-standard deviation)
      on all health-related QoL domains: psychological health (14.52+/-2.80 vs 15.94+/
      2.55), social relationships (15.12+/-3.08 vs 16.06+/-2.69), environment (12.80+/
      2.78 vs 13.87+/-2.49), as well as on a separate item of self-assessed health
      (3.33+/-1.16 vs 3.56+/-0.92) than their employed counterparts (P<0.01). This
      disparity was not found only in the domain of physical health. The largest
      positive impact on life satisfaction in both groups was family. CONCLUSION: As
      disabled women are a particularly vulnerable population group, stressing the
      importance of employment and family as factors affecting their quality of life
      may help equalizing opportunities and upgrading the quality of life of all -
      particularly unemployed women with disabilities.

PMID- 21853551
TI  - Identification of general characteristics, motivation, and satisfaction of
      internet-based medical consultation service users in Croatia.
AB  - AIM: To identify users' reasons to look for physician consultation on the
      internet instead of visiting a physician and to explore their general
      characteristics, motivation, and satisfaction with internet medical consultation
      service 'Your Questions.' METHODS: Users of a free internet medical consultation
      service 'Your Questions' (www.plivazdravlje.hr) were invited to participate in a
      web-based survey designed to explore their general characteristics (age, sex,
      etc), reasons for using the service, the nature of their health problem or
      question, and their satisfaction with the service. Respondents were divided into
      two groups: users who consulted an internet physician only (Group I) and users
      who used internet consulting before or after visiting a physician (Group II).
      RESULTS: The response rate was 38% (1036/2747), with 79% female respondents. A
      fifth of the respondents (21%) consulted an internet physician only (Group I).
      Multivariate analysis revealed that the respondents in Group I were younger
      (median 24 vs 28 years in Group II), more interested into questions about
      pregnancy (odds ratio [OR], 1.984; 95% confidence interval [CI], 1.203-3.272),
      more often embarrassed to talk to a physician in person (OR, 1.828; 95% CI, 1.119
      2.989), and more motivated to protect their privacy (OR, 1.727; 95% CI, 1.252
      2.380). They also had greater satisfaction with the service (77% vs 60%,
      P<0.001). CONCLUSION: The factors associated with the use of internet-based
      medical consultation services were younger age, need for privacy protection,
      avoidance of embarrassment at the physician's office, and having a question
      related to pregnancy. This reveals the internet medical consultation service as a
      useful health promotion supplement that is particularly applicable for the
      population of young adults.

PMID- 21853553
TI  - Plagiarism in scientific writing: words or ideas?

PMID- 21853552
TI  - Continental-Mediterranean and rural-urban differences in cardiovascular risk
      factors in Croatian population.
AB  - AIM: To compare the distribution of cardiovascular disease (CVD) factors between
      continental and Mediterranean areas and urban and rural areas of Croatia, as well
      as to investigate the differences in achieving treatment goals by the general
      practitioners (GP) in different settings. METHODS: A multicenter prospective
      study was performed on 2467 participants of both sexes >=40 years old, who
      visited for any reason 59 general practices covering the whole area of Croatia
      (May-July 2008). The study was a part of the Cardiovascular Risk and Intervention
      Study in Croatia-family medicine (CRISIC-fm) study. Patients were interviewed
      using a 140-item questionnaire on socio-demographics and CVD risk factors. We
      measured body mass index (BMI) and waist circumference and determined biochemical
      variables including blood pressure, total, high-density lipoprotein-, and low
      density lipoprotein-cholesterol, triglycerides, glycemia, and uric acid. RESULTS:
      Participants from continental rural areas had significantly higher systolic and
      diastolic blood pressure (P<0.001), obesity (P=0.001), increased waist
      circumference (P<0.001), and more intense physical activity (P=0.020).
      Participants from coastal rural areas had higher HDL-cholesterol, participants
      from continental rural and coastal urban areas had higher LDL-cholesterol, and
      participants from rural continental had significantly higher BMI and waist
      circumference. CONCLUSION: Prevalence of CVD risk factors in Croatian population
      is high. Greater burden of risk factors in continental region and rural areas may
      be partly explained by lifestyle differences.

PMID- 21853554
TI  - Eyes say more than we think.

PMID- 21853555
TI  - Findings of research misconduct.

PMID- 21853556
TI  - Clinical science: Research and repair.

PMID- 21853557
TI  - The obesity paradox.
AB  - Despite the association of obesity with increasing risk for CV diseases,
      overweight/obese patients with CV disease have the best prognosis.

PMID- 21853558
TI  - Highlights of cardiology in Hungary.
AB  - The authors discuss cardiology and their Society in this small central European
      country.

PMID- 21853559
TI  - Effects on vision with glare after correction of monochromatic wavefront
      aberrations.
AB  - PURPOSE: To investigate effects of optical aberration correction on vision with
      glare. METHODS: Correction of aberrations up to the 6th Zernike order (closed
      loop correction) was compared with conventional spectacle correction in 42
      healthy eyes. To create these corrections, an adaptive optics system including a
      thin-film transistor (TFT) monitor for displaying optotypes with additional glare
      sources was used. Employing both corrections, visual acuity and contrast
      sensitivity (CS) were tested alternately with and without glare. Disability glare
      was computed as the difference between log CS without and with glare. Individuals
      were also asked to rate subjectively the quality of three images displayed on the
      TFT monitor. RESULTS: Significant improvements of CS without and with glare were
      found with the closed-loop correction (0.147 and 0.198 log CS, respectively),
      whereas no significant difference in visual acuity was found in either
      correction. Correlations were determined between reduction of total root-mean
      square error and increase of CS with glare (Pearson correlation coefficient
      r=0.42) and decrease of disability glare (r=-0.33). Visual acuity was correlated
      with the visual Strehl ratio based on the optical transfer function (r=0.46).
      Subjective comparison of the images showed improvements more clearly. Depending
      on the image, in 57% to 78% of the eyes, closed-loop correction was rated better
      than spectacle correction. The subjective glare effect was reduced as well.
      CONCLUSIONS: Investigation of vision with glare seems to be a reasonable
      additional test to evaluate the visual outcome of a customized correction.

PMID- 21853560
TI  - Health bill. Transparency offers a chink of light in a dark week for reform.

PMID- 21853561
TI  - Commissioning board. 'NHS England' name plan proves controversial.

PMID- 21853562
TI  - Charitable assets. NHS charities 'nationalised' by treasury.

PMID- 21853563
TI  - You talked, and we listened.

PMID- 21853564
TI  - Patient power needs a turbo boost.

PMID- 21853565
TI  - Thrown a curve. CMS' actuaries: healthcare spending will continue to increase,
      despite reform law promises.
AB  - While CMS actuaries say the 2010 reform law will not slow the nation's healthcare
      spending in the coming decade, Mary Grealy, of the Healthcare Leadership Council,
      says the law "was basically a coverage bill. We just didn't get to the other
      half, which would be aimed at the cost-drivers in the system." She adds that the
      healthcare system will not control ongoing steep increases in spending until
      additional legislation reshapes the dominant public insurance plans.

PMID- 21853566
TI  - 'Cuts are on the table'. Regardless of debt deal, healthcare likely to suffer.

PMID- 21853567
TI  - Divisiveness brings uncertainty. Stem-cell researchers look elsewhere for
      funding.

PMID- 21853568
TI  - Keeping an eye out for trouble. Internal controls are key, fraud investigators
      say.

PMID- 21853569
TI  - Groups: revise disclosure rule.

PMID- 21853570
TI  - Stepping down. After 25 years, Ryan ends reign at SSM.

PMID- 21853571
TI  - A new standard. Aim for safety of planes, nuclear plants.

PMID- 21853572
TI  - Savings. Trusts reveal extent of cuts to paybill.

PMID- 21853573
TI  - Infection control. Trusts blame new C diff testing for failed targets.

PMID- 21853574
TI  - Exclusive. Dr Foster data reveals care quality disparities.

PMID- 21853575
TI  - Listen very carefully.

PMID- 21853576
TI  - At the sharp end of NHS history.

PMID- 21853577
TI  - Motivated buyer. Highmark-West Penn deal illustrates the high stakes in
      integration game.
AB  - The deal that brings together troubled West Penn Allegheny Health System and
      Highmark could cause big waves in Western Pennsylvania. "We can go to the
      physicians and go to the hospitals and say, 'We're going to start reimbursing
      based on quality metrics, outcomes, and also based on cost effectiveness.' All of
      a sudden, that incentive of being volume-driven completely goes away," says Dr.
      Tony Farah, left, of West Penn Allegheny.

PMID- 21853578
TI  - Taking sides. Reform ruling has observers facing off on future.

PMID- 21853579
TI  - HHS touts free care ... as docs say preventive services hard to bill.

PMID- 21853580
TI  - Pushing to save on costs. Speakers at ANI put focus on system changes.

PMID- 21853581
TI  - Staying strong. Accountability, reform are hot topics at AHLA.

PMID- 21853582
TI  - Zeroing in on errors. Joint Commission targets wrong-site surgery.

PMID- 21853583
TI  - Another Catholic sell-off. HMA to acquire Mercy Health Partners-Tenn.

PMID- 21853584
TI  - Information at their fingertips. Centene uses advanced analytics to help improve
      healthcare outcomes.

PMID- 21853585
TI  - Against the clock. As deadlines loom, many states competing against politics,
      regulations to set up insurance exchanges.
AB  - With a January 2014 deadline fast approaching to create health insurance
      exchanges, there are fears some states won't be able to finish all they need to
      in the tight time frame. 'Time is not our friend. 2013 is upon us," says Dr.
      Bruce Goldberg, director of the Oregon Health Authority.

PMID- 21853586
TI  - Missing piece. Studies fail to address long-term viability: NAPH.

PMID- 21853587
TI  - Sneak peek. Proposals preview needs assessment requirements.

PMID- 21853588
TI  - Conditional growth. Expansion hurdles high for doc-owned hospitals.

PMID- 21853589
TI  - Providers weigh Varney exit. Focus on antitrust laws made 'companies take
      notice'.

PMID- 21853590
TI  - Execs may face retrial.

PMID- 21853591
TI  - On the rise. Strong returns show pre-recession business reviving.

PMID- 21853592
TI  - The clock is ticking. Debt talks put bull's-eye on health spending, but how much
      pain is necessary?

PMID- 21853593
TI  - Similar concerns. Safety, costs among the issues to be weighed as FDA grapples
      with crafting an approval process for generic versions of biological medicines.

PMID- 21853594
TI  - Fight for independence. Independent Payment Advisory Board has politicians,
      hospitals and physicians riled up while questions abound over the panel's future.
AB  - The proposed Independent Payment Advisory Board has set off a furor, with
      politicians from both sides of the aisle, physicians and hospitals all seeking to
      stop it. Concerns vary from fear over reimbursement cuts to impinging on
      Congress' authority. "How can IPAB impose sharp cuts to providers without any
      adverse impact on their patients?" Rep. Paul Ryan, asked last week during a
      hearing on Capitol Hill.

PMID- 21853595
TI  - No guarantees. Provider cuts still an option under any debt deal.

PMID- 21853596
TI  - Facing a downgrade. Debt debate threatens hospital loans' credit ratings.

PMID- 21853597
TI  - GAO blasts CMS for fraud-fighting tool delay.

PMID- 21853598
TI  - Which law applies? Debate over how to review HCA-HealthOne deal.

PMID- 21853599
TI  - Drug shortages lead to action.

PMID- 21853600
TI  - Don't darken U.S. health. The unbearable lightness of politicians dealing with
      bulbs and deficits.

PMID- 21853601
TI  - Largest healthcare services mergers/acquisitions in 2010. Completed or pending
      U.S. transactions ranked by the deal's price.

PMID- 21853602
TI  - How the health care reform law affects APRNs.

PMID- 21853603
TI  - Saving it for later. Healthy hospitals turn to layoffs to bend own cost curve.
AB  - When the credit crisis hit in 2008, many hospitals reacted by cutting staff.
      While credit access and the markets may have rebounded, hospital spending hasn't
      and some are still looking for cuts. Dennis Dahlen, of Banner Health, recently
      told the health system's investors that executives will "plan for the worst and
      work for the best."

PMID- 21853604
TI  - Data-mining law struck down. Supreme court sides with drug companies in Vermont
      ruling.

PMID- 21853605
TI  - CMS scales back appeal rules.

PMID- 21853606
TI  - Vanguard IPO comes in low.

PMID- 21853607
TI  - Going global. FDA moves to deal with growing raft of imports.

PMID- 21853608
TI  - Action plan. IOM report lauded, but may be hard to implement.

PMID- 21853609
TI  - Fewer alternatives? Ancillary businesses become less of a focus for some
      hospitals and health systems, but they still fill a niche, and many organizations
      see financial, operational advantages.

PMID- 21853610
TI  - [Determination of melatonin in biological fluids].
AB  - The review considers main approaches to solving the problem in the quantification
      of melatonin and describes physicochemical and biological methods for melatonin
      determination in biological fluids (saliva, urine, plasma) and tissues. The
      impetus to writing this paper came from the considerably growing interest of the
      scientific community in melatonin and the in-depth studies of its physiological
      role, which had revealed a diversity of its previously unknown most important
      functions and confirmed its presence in many compartments of the body. Due to the
      specificity of its molecular structure and low concentration, melatonin remains
      invisible for many conventional analyses. The way out may be combination
      detection that involves the benefits of a few procedures and that has emerged at
      the interface of various sciences.

PMID- 21853611
TI  - [Comparison of sevoflurane and propofol anesthesia for aortocoronary bypass
      surgery without artificial circulation].
AB  - The purpose of the study was to compare the effectiveness of sevoflurane and
      propofol during combined anesthesia with epidural component during aortocoronary
      bypass surgery without artificial circulation. MATERIALS AND METHODS: The study
      included 24 patients with ischemic heart disease. All patients underwent
      aortocoronary bypass surgery on the working heart (from 1 to 5 bypasses) under
      combined anesthesia (propofol or sevoflurane with epidural anesthesia with the
      use of ropicavaine and fentanyl). Induction of anesthesia was carried out by
      midasolam 0.06 mg/kg, propofol 1-1.5 mg/kg, fentanyl 2.5 mcg/kg, myorelaxation
      was reached by pipecuronium bromide 0.1 mg/kg. Patients were randomized into
      propofol group (n = 12) and sevoflurane group (n = 12). Both groups received low
      flow anesthesia (1l/min) with the use of Drager Primus anesthesia workstation.
      Anesthesia in the first group was maintained by propofol 3-5 mg/kg/h, in the
      second group by sevoflurane 0.5-3 vol.%. In both groups additional fentanyl was
      administered in the dose of 1.2 -1.5 mcg/kg/h. RESULTS: In the postoperative
      period the increase of the stroke volume and decrease of blood plasma lactate
      were noticed in the sevoflurane group. The postoperative pain, 6 hours after the
      aortocoronary bypass surgery in the control group was evidently higher according
      to Visual Analogue Scale. CONCLUSION: Use of sevorane as a component of combined
      anesthesia during aortocoronary bypass surgery allows to improve the performance
      of the myocardium, reduce the severity of hypoperfusion in the perioperative
      period and reduce the severity of pain after the surgery compared to propofol
      anesthesia.

PMID- 21853612
TI  - [The role of magnesium in the implementation of vascular reactions during
      anesthesia in cardiac surgery patients].
AB  - The purpose of the study is to examine the relationship between the concentration
      of magnesium in plasma and vascular reactions during cardiac surgery. MATERIALS
      AND METHODS: The study included 77 patients with coronary artery disease who
      underwent myocardial revascularization surgery. In the first group (n = 44)
      during the entire operation infusion solution "potassium and magnesium
      asparginate" (Berlin-Chemie) was carried out at a rate of 1.5-2 ml/kg/h, in the
      second group (n = 33) patients were injected magnesium free crystalloid
      solutions. An analysis of central hemodynamics (PiCCO Plus) and microcirculation
      (laser Doppler flowmetry LASMA) was carried out. CONCLUSION: Maintenance of
      normal concentrations of magnesium in blood plasma reduces the incidence of
      episodes of intraoperative hypertension and improves peripheral microcirculation.

PMID- 21853614
TI  - Endocannabinoids are expressed in bone marrow stromal niches and play a role in
      interactions of hematopoietic stem and progenitor cells with the bone marrow
      microenvironment.

PMID- 21853613
TI  - [Changes of salivary alpha amylase activity as an indicator of adrenergic
      activity in response to laryngoscopy and endotracheal intubation].
AB  - The goal of the study was to determine the diagnostic value of the salivary alpha
      amylase (sAA) as an indicator of adrenergic activity in response to laryngoscopy
      and endotracheal intubation. The research group consisted of 52 patients (ASA 1
      2) with the median age of 52 +/- 16, scheduled for elective orotracheal
      intubation by the means of standard intravenous induction of anesthesia. sAA and
      cortisol in saliva as well as norepinephrine (NA) and cortisol levels in plasma
      were determined in two points: immediately before laryngoscopy (point A) and one
      minute after intubation (point B). The heart rate (HR) and mean arterial pressure
      (MAP) were recorded in corresponding time points to reveal if any correlation
      existed between hemodynamic parameters and neuroendocrine response. The results
      showed that MAP significantly increased in point B compared to point A, p < 0.05.
      HR did not show any significant increase. sAA considerable increase in point B
      correlated with the MAP-shown increase in the same time point (r(s) = 0.328, p <
      0.05). NA increased in point B compared to point A and correlated with sAA
      increase (r(s) = 0.456, p < 0.01) and MAP changes (r(s) = 0.469, p < 0.01).
      Cortisol levels both in saliva and plasma did not change. The research proved the
      increased level of sAA as an adrenergic activity response to laryngoscopy and
      endotracheal intubation and shown it resemblance to changes of NA and MAP.

PMID- 21853615
TI  - The credibility of research.
AB  - Cardiology trumps most medical fields for credibility of research,but there is
      still room for improvement.

PMID- 21853617
TI  - Family violence and football: the effect of unexpected emotional cues on violent
      behavior.
AB  - We study the link between family violence and the emotional cues associated with
      wins and losses by professional football teams. We hypothesize that the risk of
      violence is affected by the "gain-loss" utility of game outcomes around a
      rationally expected reference point. Our empirical analysis uses police reports
      of violent incidents on Sundays during the professional football season.
      Controlling for the pregame point spread and the size of the local viewing
      audience, we find that upset losses (defeats when the home team was predicted to
      win by four or more points) lead to a 10% increase in the rate of at-home
      violence by men against their wives and girlfriends. In contrast, losses when the
      game was expected to be close have small and insignificant effects. Upset wins
      (victories when the home team was predicted to lose) also have little impact on
      violence, consistent with asymmetry in the gain-loss utility function. The rise
      in violence after an upset loss is concentrated in a narrow time window near the
      end of the game and is larger for more important games. We find no evidence for
      reference point updating based on the halftime score.

PMID- 21853618
TI  - Spring cleaning: rural water impacts, valuation, and property rights
      institutions.
AB  - Using a randomized evaluation in Kenya, we measure health impacts of spring
      protection, an investment that improves source water quality. We also estimate
      households' valuation of spring protection and simulate the welfare impacts of
      alternatives to the current system of common property rights in water, which
      limits incentives for private investment. Spring infrastructure investments
      reduce fecal contamination by 66%, but household water quality improves less, due
      to recontamination. Child diarrhea falls by one quarter. Travel-cost based
      revealed preference estimates of households' valuations are much smaller than
      both stated preference valuations and health planners' valuations, and are
      consistent with models in which the demand for health is highly income elastic.
      We estimate that private property norms would generate little additional
      investment while imposing large static costs due to above-marginal-cost pricing,
      private property would function better at higher income levels or under water
      scarcity, and alternative institutions could yield Pareto improvements.

PMID- 21853619
TI  - Within salvation: girl hawkers and the colonial state in development era Lagos.
AB  - For almost two decades between the close of the Second World War and Nigerian
      independence in 1960, the British colonial state which faced a crisis of
      legitimacy in Lagos upheld city ordinances that made itinerant trading by young
      children in Lagos a punishable status offense. Although anti-trading regulations
      were gender-neutral in their language, girls were disproportionately sanctioned
      for engaging in street trading and related activities. In defending their
      concentration on girl sellers over boy sellers, colonial welfare officials
      painted a picture of the urban context as an inherently dangerous context and of
      girls as being particularly at risk of violent assault in the city, making them
      particularly in need of protection from town life. Sources which show that
      parents generally resisted or ignored the street trading regulations and
      continued permitting their daughters to sell despite entreaties, warnings, or
      fines from colonial officials, suggest that African parents and British colonial
      officials may have had conflicting views on the inherent danger of the city, on
      what constituted child endangerment, and on the gendered nature of childhood.
      This article argues that the girl saving campaigns of development era Lagos were
      as much about the legitimization of a colonial state facing a crisis of
      legitimacy as they were about debates between African parents and colonial
      welfare officials in Lagos concerning ideas of children and childhood and the
      dangers of street trading by African girls.

PMID- 21853621
TI  - "Mulata, Hija de Negro y India": Afro-Indigenous Mulatos in early colonial
      Mexico.
AB  - Since the fifteenth century, the term "mulato" has been used to describe
      individuals of mixed African and European ancestry. Through an examination of
      mulatos from sixteenth century New Spain this piece complicates our understanding
      of the usage and implication of this socio-racial ascription. Both demographic
      and anecdotal evidence suggests that in the early colonial period mulato
      frequently described individuals of mixed African-indigenous ancestry. Moreover,
      these individuals may have represented the majority of individuals so named.
      Additionally this piece uses several case studies to demonstrate that Afro
      indigenous mulatos formed frequent and long-term connections to indigenous
      society and culture. Through acculturation and familial ties, early mulatos
      helped to encourage interethnic unions and may have played a key role in the
      growth of a highly varied, multi-ethnic colonial population in Mexico. By
      highlighting these important trends, this study challenges our traditional
      assumptions concerning the category of mulato and suggests that we must avoid the
      homogenizing tendency inherent in such terminology.

PMID- 21853622
TI  - Who were his peers? The social and professional milieu of the provincial surgeon
      apothecary in the late-eighteenth century.
AB  - The social standing of the surgeon-apothecary cannot be determined by reference
      to professional life alone, yet few such men left social documents. The lower
      middling sort was typically reticent about evaluations of their own social
      position in any source genre. This article uses a unique archive, and the concept
      of community connectedness, to investigate the status of Thomas Higgins, surgeon
      apothecary and man-midwife of north Shropshire. Higgins embodied the traditional
      practitioner who relied on local knowledge and his 'friends' for advancement, in
      contrast to alternative modes of rising professionalism. He was demonstrably a
      trusted man at the heart of his home town, but his reliance on the 'partiality'
      of his neighbors brought him into conflict with his colleagues.

PMID- 21853623
TI  - The impact of urbanization on family structure: the experience of Sarawak,
      Malaysia.
AB  - This paper argues that women and men encounter the processes of migration and
      urbanization in very gendered ways. It examines state development policies and
      their role in accelerating the pace of urbanization, Using material from a
      recently concluded study on single mothers in the lower socio-economic strata,
      this paper explores the impact of these wider processes on the structure of the
      family and women from this strata specifically.

PMID- 21853624
TI  - Violent youth groups in Indonesia: the cases of Yogyakarta and Nusa Tenggara
      Barat.
AB  - Problems of violent youth groups have escalated in Indonesia, following economic
      recession, unemployment, and weakened state institutions. Young people have been
      hit by the lack of income and broken expectations. In consequence, youth groups
      emerge and arrange for members' economic revenue as well as identity creation and
      confidence. Religion in some cases is used to legitimize violence and to
      strengthen the boldness of group members. The paper offers a brief overview of
      gangster (preman) traditions in Indonesia. Empirical findings on violent youth
      groups in the two selected provinces are presented within a multi-factor
      analytical framework, where the need for income and identity strengthening,
      political elite interests, and the lack of law enforcement contribute to
      explaining criminal and vigilante violence. Interviews with leaders and members
      of movements engaged in violent actions offer insights into a problem that
      threatens national security and control.

PMID- 21853625
TI  - Carter Center report envisions integrated care at the heart of a reinvented
      primary care system.

PMID- 21853626
TI  - Fraud convictions reflect adversely on doctor's fitness to practise.

PMID- 21853627
TI  - Outbreak news. Outbreak of illness in schools, Angola.

PMID- 21853628
TI  - Neglected zoonotic diseases: report from the third international conference,
      November 2010.

PMID- 21853629
TI  - Yellow fever in the WHO African and American Regions, 2010.

PMID- 21853630
TI  - The history of the libido's development: evidence from Freud's case studies.
AB  - Between 1905 and 1911 a perspective slowly appeared in Freud's works -- a
      perspective which he considered "historical" and which he eventually named
      "history of the libido's development" ("Entwicklungsgeschichte der Libido") in
      1911. By reading again "The Rate Man," "Schreber" and "The Wolf Man" we can
      understand how Freud, thanks to the analysis of his case histories, outlined the
      particularities of this "history of the libido's development," which lies at the
      core of infantile prehistory. We will also study how this "history of the
      libido's development," in providing a stereotyped interpretation of psychic
      material, could lead to a reduction of the very movement of the analysis.

PMID- 21853631
TI  - Simulating the unconscious.
AB  - This paper is concerned with hypnosis and the methodological "anxiety" (Devereux)
      which inevitably affects the hypnotist, whether experimental psychologist or
      therapist: what if the phenomena observed during hypnosis were only an effect of
      compliance with his own expectations, demands and suggestions? What if the
      hypnotized simulated hypnosis solely to please him? From Charcot and Richet to
      Martin Orne, by way of Bernheim or Freud, the response of researchers to this
      disquieting question has always been the same: the subject cannot be simulating,
      because he is hypnotized, asleep, unconscious. The hypothesis of a psychic
      unconscious (or of unconsciousness), which determined the very concept of
      hypnosis from the second half of the nineteenth century onwards is nothing more
      than a postulate required to guarantee the objectivity of hypnotic and, more
      broadly, psychological phenomena, by preventing the latter from being seen as
      simple artifacts of the experimental or clinical situation. The present paper
      examines several historical avatars of this postulate, including psychoanalysis,
      and proposes that it be abandoned in favor of a conception of psychology and
      psychotherapy which is constructivist and no longer objectivist, recognizing the
      artifactual character of psychic productions instead of denying it.

PMID- 21853633
TI  - Dynamics of Critical Care 2010, Edmonton, Alberta, September 19-21, 2010.
      Abstracts.

PMID- 21853632
TI  - Rising hospital employment of physicians: better quality, higher costs?
AB  - In a quest to gain market share, hospital employment of physicians has
      accelerated in recent years to shore up referral bases and capture admissions,
      according to the Center for Studying Health System Change's (HSC) 2010 site
      visits to 12 nationally representative metropolitan communities. Stagnant
      reimbursement rates, coupled with the rising costs of private practice, and a
      desire for a better work-life balance have contributed to physician interest in
      hospital employment. While greater physician alignment with hospitals may improve
      quality through better clinical integration and care coordination, hospital
      employment of physicians does not guarantee clinical integration. The trend of
      hospital-employed physicians also may increase costs through higher hospital and
      physician commercial insurance payment rates and hospital pressure on employed
      physicians to order more expensive care. To date, hospitals' primary motivation
      for employing physicians has been to gain market share, typically through
      lucrative service-line strategies encouraged by a fee-for-service payment system
      that rewards volume. More recently, hospitals view physician employment as a way
      to prepare for payment reforms that shift from fee for service to methods that
      make providers more accountable for the cost and quality of patient care.

PMID- 21853634
TI  - Beneath the surface.

PMID- 21853635
TI  - How do NPs and PAs get information and learn?

PMID- 21853636
TI  - Presenting at conferences: rewarding, start to finish.

PMID- 21853637
TI  - NPs, PAs and malpractice insurance policies.

PMID- 21853638
TI  - Hormone Therapy for menopause: a concise update of the benefits and risks.

PMID- 21853639
TI  - Best face forward: a commonsense guide to acne treatment.

PMID- 21853640
TI  - Toward better COPD management: practical aspects of inhaler use.

PMID- 21853641
TI  - Who should be vaccinated against HPV? The list continues to grow.

PMID- 21853642
TI  - When heartburn gets serious: an update on Barrett's esophagus.

PMID- 21853643
TI  - Sports physicals in convenient care.

PMID- 21853644
TI  - Self-expression through body art: equipping adolescents to make smart decisions.

PMID- 21853645
TI  - Uterine fibroids: clinical and surgical management.

PMID- 21853646
TI  - NPs and PAs in the news.

PMID- 21853647
TI  - Meconium aspiration syndrome: do we know?
AB  - Meconium is a common finding in amniotic fluid and placental specimens,
      particularly in the term or post-term pregnancy. The most important consequence
      of meconium-stained amniotic fluid (MSAF) is meconium aspiration syndrome (MAS),
      and at least 5% of infants born through MSAF develop MAS. MAS continues to be a
      threat to many newborns throughout the world, with a case fatality rate of 5% (as
      much as 40%), in addition to short- and long-term pulmonary and
      neurodevelopmental sequelae. The exact pathophysiology of meconium passage into
      the amniotic fluid and consequences of meconium aspiration are unknown. There are
      three prevailing and possibly compatible theories for mechanisms of meconium
      release. Firstly, meconium passage is probably related with the maturation of the
      gastrointestinal tract, because meconium passage in the preterm third trimester
      fetus has been reported to be a rare event, as typically it occurs near or post
      term. Secondly, an alternate hypothesis for in utero meconium passage is that
      pathologic processes, such as stress via hypoxia or infection, can trigger
      meconium passage. However, the predictive values of MSAF for fetal distress and
      acidosis at birth are poor and controversial. Thirdly, an alternative route for
      the presence of MSAF in the presence of fetal hypoxia is reduced clearance of
      defecated meconium due to impaired fetal swallowing or unidentified placental
      dysfunction in addition to or instead of an increase in its passage. The
      pathophysiology of MAS is multifactorial and extremely complex. Meconium causes
      mechanical obstruction and pulmonary air leak, induces surfactant inactivation,
      causes pulmonary inflammation, and induces apoptosis. Preventing prolonged
      pregnancy by labor induction might reduce the risk of MSAF. Labor induction with
      prostaglandins appears to be associated with the occurrence of MSAF.
      Amnioinfusion for suspected umbilical cord compression has no clear effect on the
      occurrence of MSAF. Intrapartum suctioning of the naso- and oropharynx before
      delivery of the shoulders as well as postnatal endotracheal suctioning of
      vigorous infants with MSAF are no longer recommended. Currently, endotracheal
      suction is recommended only in neonates born through MSAF who are not vigorous at
      birth. Indications for mechanical ventilation in infants with MAS are arbitrary.
      Surfactant administration may reduce the severity of MAS. Bronchoalveolar lavage
      with surfactant in infants with MAS is risky and it cannot be recommended for
      routine use. At present, there is insufficient evidence to propose routine
      steroid therapy in the management of MAS. Although prophylactic antibiotics in
      infants with MAS are not justified, most of these patients receive antibiotics
      during the first days of life, before the diagnosis of pneumonia can be
      completely ruled out. Children surviving severe MAS are in fact reported to have
      higher prevalence of asthmatic symptoms and bronchiolar hyperreactivity than
      children in the general population. It remains undetermined how often and at what
      intensity systemic inflammation occurs in association with MAS and what its
      significance is for the outcome of infants with severe MAS.

PMID- 21853648
TI  - Glucose-6-phosphate dehydrogenase activity, structure, molecular characteristics
      and role in neonatal hyperbilirubinemia in cord blood in Cukurova region.
AB  - The most common causes of neonatal indirect hyperbilirubinemia are blood
      incompatibility and erythrocyte enzyme defects. Glucose-6-phosphate dehydrogenase
      (G6PD) is a guarantee of erythrocyte stability and capability of existence of red
      cells. We present here the results of a study on the effect of enzyme kinetics
      and different mutations on neonatal hyperbilirubinemia in the Cukurova region.
      Two hundred healthy term male neonates born in Cukurova University Balcall
      Hospital, Adana Maternity Hospital and Cukurova Maternal and Children's Hospital
      between 1 November 2004 and 30 November 2007 were consecutively studied. Nanogen
      DNA microarray was used to determine Gd Union, Gd San, Gd Mediterranean, and Gd
      San Antonio mutations. Quantitative G6PD enzyme assays were performed. Glucose-6
      phosphate dehydrogenase deficiency was detected in six out of 200 male neonates
      (3%). The other 194 neonates had normal G6PD activity, with a mean of 8.3 +/- 2.1
      IU/g hemoglobin (Hb) (5.2-12.7 IU/g Hb). Clinical follow-up, enzyme kinetics and
      genetic studies were performed in the G6PD-deficient neonates. Differences were
      observed in clinical outcomes, rates of bilirubin decline and maximum total
      bilirubin levels in the neonates having the same mutation. These differences
      might be caused by the effects of kinetic variant on the hyperbilirubinemia
      without the direct effect of the mutation. In future studies, mutation analyses
      of further G6PD-deficient cases may address the genotype differences and their
      clinical effects in G6PD-deficient patients.

PMID- 21853649
TI  - Preliminary results of propranolol treatment for patients with infantile
      hemangioma.
AB  - Propranolol, a non-selective beta-blocker, has recently been introduced as a
      treatment for infantile hemangiomas. In this study, we evaluated the effect of
      propranolol in 12 infants with hemangioma. Twelve infants (9 girls) with a median
      age of 4.5 months were included in the study. All of the patients in the study
      group received short-term (1-9 weeks, median: 4 weeks) systemic corticosteroids
      as a first-line therapy. All patients received propranolol 2 mg/kg/day, divided
      into three doses. They were treated in an inpatient setting for the first 72
      hours of the treatment. Vital signs, blood pressure and blood glucose were
      monitored. Propranolol treatment was given for 4-9 months (median: 5 months). In
      the study group, regression rate of the mean dimension of the lesion was 38% +/-
      15 (range 15%-50, median 45%) at the 2nd month of therapy. Over 9 months, which
      was the maximum follow-up period, the regression rate of the mean dimension of
      the lesion was 55% +/- 31 (range 20%-80, median 50%). One patient had transient
      bradycardia, which improved spontaneously. No other side effect was observed in
      the study population. Propranolol appears to be an effective drug for infantile
      hemangiomas with good clinical tolerance. We suggest that propranolol is the
      preferable drug as the first-line therapy for infantile hemangiomas.

PMID- 21853650
TI  - Pneumococcal meningitis in the newborn period in a prevaccination era: a 10-year
      experience at a tertiary intensive care unit.
AB  - There are few data with respect to pneumococcal meningitis in neonates.
      Epidemiological aspects, clinical features and outcomes in newborn infants
      diagnosed with pneumococcal meningitis were evaluated in this study. Nineteen
      newborn infants in a neonatal intensive care unit diagnosed with culture-proven
      community-acquired bacterial meningitis between January 1999 and December 2008
      were reviewed, and of them, eight patients were diagnosed as pneumococcal
      meningitis. Overall, among 10,186 hospitalized newborn infants, 132 community
      acquired sepsis/meningitis cases (1.3%) were suspected, and blood cultures were
      performed in all, while cerebrospinal fluid (CSF) cultures could be performed in
      124 cases. Rate of blood culture positivity was 45%. Nineteen (15.3%) of 124 were
      diagnosed as culture-proven community-acquired bacterial meningitis, which was
      confirmed by CSF growth. Eight (42.1%) of 19 had pneumococcal meningitis. In
      pneumococcal cases, abundant Gram-positive diplococci were seen on CSF smear and
      Streptococcus pneumoniae was isolated from CSF cultures. All isolates were
      susceptible to penicillin and third-generation cephalosporins. Irritability (n:
      7), poor sucking (n: 7) and fever (n: 6) were the principal findings on the
      initial physical examination. Of all patients with pneumococcal meningitis, four
      were initially given cefotaxime plus amikacin treatment, and the remaining four
      were initially given cefotaxime plus ampicillin plus vancomycin. Antibiotic
      treatment in two patients was revised during their clinical course. Additionally,
      in three patients, vancomycin and ampicillin was discontinued on the third day
      when antibiogram of CSF cultures revealed penicillin sensitivity. Overall,
      mortality in pneumococcal meningitis was 50%. In the surviving patients, two had
      epilepsy, one sensorineural hearing loss, and two mental-motor retardation.
      Pneumococcal meningitis was the leading cause of community-acquired neonatal
      meningitis in our patients. Immunization against pneumococcal disease in
      developing countries would be beneficial for public health and for newborn
      infants.

PMID- 21853651
TI  - Home visits in phenylketonuria: a 12-month longitudinal study.
AB  - This study aimed to evaluate the effect of dietary education given to the
      caregivers of children with phenylketonuria (PKU) in their home environment on
      children's blood phenylalanine (Phe) levels. Thirty-six children with PKU, aged 2
      12 years, were recruited. Each caregiver was visited on three separate occasions
      and given a detailed dietary education. Fasting morning skin puncture blood
      samples were collected on Newborn Screening Blood Test filter paper for Phe
      analysis at baseline and 1, 4, 12, 24, and 48 weeks after the home visits. The
      mean baseline blood Phe level (365 +/- 232 micromol/L) significantly decreased
      with home visits at the 1st week (314 +/- 226 micromol/L) (p < 0.05). Four weeks
      after the home visits, the median blood Phe level was still lower than baseline,
      but the difference was not statistically significant (p > 0.05). The mean blood
      Phe levels significantly increased at the end of the 12th, 24th and 48th weeks
      (329 +/- 230 micromol/L; 447 +/- 189 micromol/L and 486 +/- 261 micromol/L,
      respectively) (p < 0.05). A well-controlled blood Phe level can be achieved with
      intense, regular and continuing education programs, which include regular home
      visits.

PMID- 21853652
TI  - Visceral leishmaniasis in children: a cohort of 120 patients in a metropolitan
      city of Brazil.
AB  - There are few studies regarding the clinical presentation of visceral
      leishmaniasis (VL) in children. The aim of this study was to investigate the
      clinical manifestations, major complications and causes of death in children with
      VL. A retrospective study was performed with pediatric patients (< or = 14 years
      old) with a diagnosis of VL in Fortaleza, state of Ceara, in Northeast Brazil. A
      total of 120 patients were included. The mean age was 5 +/- 3.9 years, and 53.4%
      were male. The main clinical manifestations at admission were: fever (94.2%),
      splenomegaly (94.2%), hepatomegaly (82.5%), anorexia (55%), malaise (47.5%),
      cough (41.6%), abdominal pain (27.5%), vomiting (25.5%), and diarrhea (16.6%).
      Acute kidney injury was found in 25% of the patients. The main complication
      during hospital stay was pulmonary infection, found in 27.5% (n = 33), leading to
      sepsis in 3 cases. Glucantime was the drug of choice in 90% (n = 108) of the
      cases, amphotericin B in 7.5% (n = 9) and AmBisome in 2.5% (n = 3). Death
      occurred in 4 cases (3.3%) due to sepsis (3 cases) and hemorrhagic complications
      (1 case). Visceral leishmaniasis is a frequent infection among children in our
      region. The main complications were pulmonary infection and acute kidney injury
      related to antiparasitic therapy, along with sepsis and hemorrhage.

PMID- 21853653
TI  - The goiter prevalence and urinary iodine levels among adolescents.
AB  - Endemic goiter and iodine deficiency are among the worldwide major public health
      problems of today. We aimed to research the goiter prevalence and the urinary
      iodine level of school children. In this descriptive study, 1,847 school children
      in Konya aged between 10 and 18 years were included. Urinary iodine level was
      measured. The mean value of iodine excretion in urine was 198 +/- 46.61 microg/L.
      In 40 students (2.2%), the urinary iodine level was < 100 microg/L. Six of these
      students (0.3%) had moderate iodine deficiency. Thyroid hyperplasia was found
      with palpation method in 128 students (6.9%). Ultrasonographically, five female
      students had solid nodule, and one male student had multiple nodules. In our
      study, no severe iodine deficiency was found. According to the results of our
      study, the mandatory iodization program in Konya has been conducted successfully.

PMID- 21853654
TI  - Ponderal index of large-for-gestational age infants: comparison between infants
      of diabetic and non-diabetic mothers.
AB  - Ponderal index (PI) is a weight-height related parameter that is mainly used to
      assess the pattern of fetal growth in small-for-gestational age infants. We aimed
      to use PI for large-for-gestational age (LGA) infants who were born to diabetic
      or non-diabetic mothers, in order to predict the fetal growth pattern. One
      hundred sixty-six LGA infants born at the Department of Obstetrics, Hacettepe
      University Hospital, Ankara, Turkey were included in the study. The PI was
      calculated by using the following formula: PI = weight (g) x 100/(height, cm)3.
      Sixty-seven (40%) of these infants were born to diabetic mothers. Maternal age,
      maternal weight and maternal weight gain during pregnancy were similar in the
      diabetic and non-diabetic groups. Mean birthweight, height and head circumference
      were similar in both groups, but median PI of infants of diabetic mothers was
      significantly higher than of infants of non-diabetic mothers (3.02 and 2.89,
      respectively, p < 0.05). Fetal growth was different between LGA infants of
      diabetic and non-diabetic mothers, and PI provided useful information on the
      proportionality of fetal growth in LGA infants.

PMID- 21853655
TI  - Clinical features of neonates treated in the intensive care unit for respiratory
      distress.
AB  - The aim of this study was to determine the indications for hospitalization,
      clinical features, and risk factors in neonates treated in the intensive care
      unit (ICU) for respiratory distress. Patients who were treated in the neonatal
      intensive care unit (NICU) for respiratory distress between 1 January 2008 and 31
      December 2008 were included in the study. The indications for hospitalization,
      duration of hospitalization, clinical features, risk factors, maternal age,
      number of pregnancies, duration of antibiotic treatment, and mortality rate were
      retrospectively obtained from hospital records and evaluated. The medical records
      of 240 neonates treated in the ICU during a one-year period were evaluated. Of
      the neonates, 64.6% were boys, 20.4% were premature, and 71.7% were born by
      cesarean section. The most frequent indication for hospitalization was tachypnea
      of the newborn (76.7%). Meconium aspiration syndrome and respiratory distress
      syndrome were also among the frequent indications for admission to the NICU.
      Recognition of risk factors for respiratory distress in neonates is crucial for
      development of prevention and early treatment strategies, and correct timing of
      elective cesarean sections is important for reduction in morbidity and mortality.

PMID- 21853656
TI  - Procalcitonin versus CRP as an early indicator of fetal infection in preterm
      premature rupture of membranes.
AB  - The aim of this study was to examine the diagnostic sensitivity and specificity
      of C-reactive protein (CRP) and procalcitonin (PCT) in neonates who were born
      after preterm premature rupture of membranes (PPROM) and compare these with
      interleukin-6 (IL-6). The study involved 74 preterm neonates who were born after
      PPROM. IL-6, CRP, complete blood count and leukocyte ratios, and PCT levels were
      measured in the 1st day of life, and CRP, PCT, and blood counts were repeated on
      the 3rd day of life. Seventy-four infants with PPROM were divided into two groups
      according to the development of sepsis and infection (Group 1: sepsis, n = 32;
      Group 2: no sepsis, n = 42). There were no significant differences between these
      groups with respect to gestational age, birthweight and duration of membrane
      rupture. There were significant differences between the two groups in the 1st day
      CRP (Group 1: 0.85 -/+ 1.36 mg/dl, Group 2: 0.23 +/- 0.25 mg/dl; p = 0.016), 1st
      day PCT (Group 1: 7.2 +/- 7.6 ng/ml, Group 2, 1.6 +/- 4.0 ng/ml; p < 0.001), and
      3rd day PCT (Group 1: 9.01 +/-11.5 ng/ml, Group 2: 1.34 +/- 1.35 ng/ml; p =
      0.001) and IL-6 (Group 1: 80.7 +/- 67.2 pg/ml, Group 2: 3.4 +/- 3.5 ng/ml; p <
      0.001) levels. CRP levels were not significantly different between Group 1 (1.2
      +/- 1.7 mg/dl) and Group 2 (0.58 +/- 1.1 mg/dl) on the 3rd day of life (p=0.059).
      CRP levels on the 1st day of life had a cut-off value of 0.72 mg/dl with a
      sensitivity and specificity of 56% and 58%, respectively. CRP levels on the 3rd
      day had a cut-off level of 0.78 mg/dl with 60% sensitivity and 63% specificity.
      PCT levels had a cut-off level of 1.74 ng/ml with 76% sensitivity and 85%
      specificity on the 1st day of life, and of 1.8 with 89% sensitivity and 86%
      specificity on the 3rd day of life. Statistical analysis revealed that the cut
      off value of 7.6 pg/ml for IL-6 had a 93% sensitivity and 96.7% specificity.
      Interleukin (IL)-6 is the most reliable marker for the detection of early-onset
      sepsis in preterm neonates with PPROM. Early PCT levels seemed to be more
      sensitive than early CRP in this population.

PMID- 21853657
TI  - Is the prophylaxis of patent ductus arteriosus useful in extremely premature
      infants?
AB  - This study was aimed to verify the efficacy and safety of ibuprofen prophylaxis
      of patent ductus arteriosus in very preterm infants, in order to select infants
      receiving higher benefits from this intervention. Two hundred neonates with
      gestational age (GA) < or = 28 weeks receiving ibuprofen within the first two
      hours of life were included. Ductus closure rate was 68%, and results were
      significantly dependent on GA (48.8% among neonates with GA < 26 weeks vs 73.2%
      among those with GA > or = 26 weeks, p < 0.01). Neonates with GA < 26 weeks
      showed a lower ductus closure after the primary course of therapy (20% vs 57.5%,
      p < 0.01), as well as higher reopening rate (16.2% vs 3.8%, p < 0.05) and need
      for surgical ligation (38.8% vs 5.8%, p < 0.01). During the prophylaxis period,
      11 neonates (5.5%) showed pulmonary hypertension. Considering risks/benefits, we
      recommend prophylaxis only in infants with GA < 26 weeks.

PMID- 21853658
TI  - Three cases of a rare disease, congenital chloride diarrhea, summons up the
      variation in the clinical course and significance of early diagnosis and adequate
      treatment in the prevention of intellectual disability.
AB  - Congenital chloride diarrhea (CLD) (OMIM #214700) is a rare, autosomal recessive
      disease that is characterized by increased chloride loss in stool. As a result of
      electrolyte loss, surviving patients might have some complications, one of them
      being mental retardation. Here, we present three new Turkish patients with new
      mutations in the SLC26A3 gene. Although the clinical picture of the patients
      might be similar, consequences of the disease and complications might differ
      greatly among patients. Pediatricians should be aware of CLD as a potentially
      fatal or disabling disease if untreated. History of polyhydramnios, watery
      diarrhea, failure to thrive, poor growth, soiling, metabolic alkalosis and
      hypokalemia/hypochloremia should be an alarming set of findings for the
      diagnosis. Salt substitution therapy started early in life prevents early
      complications, allows normal growth and development, and favors good long-term
      prognosis.

PMID- 21853659
TI  - Oropharyngeal tularemia mimicking tumoral relapse in a patient with Hodgkin
      lymphoma in remission.
AB  - Tularemia is a zoonotic disease caused by Francisella tularensis. The clinical
      forms mostly depend on the port of entry into humans. Ingestion typically results
      in the oropharyngeal form and is associated with symptoms such as fever,
      pharyngitis, cervical lymphadenitis, and suppuration. In this report, we describe
      a child treated for Hodgkin's disease presenting six years later with a left
      cervical lymphadenopathy mimicking a relapse.

PMID- 21853660
TI  - Disseminated leishmaniasis in a four-year-old child in Yaounde, Cameroon.
AB  - Leishmaniasis is a disease caused by a protozoan parasite of the genus leishmania
      with worldwide distribution and is transmitted to man by phlebotomine sand flies.
      The clinical presentation could range from a single cutaneous ulcer to
      disseminated leishmaniasis. We report the case of a four-year-old boy admitted to
      our hospital with ulcers, wasting, progressively distending abdomen, and fatigue
      evolving for about two months. On admission, he was febrile and pale, with
      diffuse oozing wet ulcers on the limbs and face, hepatosplenomegaly, and enlarged
      inguinal lymph nodes. The complete blood count revealed pancytopenia with low
      reticulocyte count, and serum protein electrophoresis showed hypoalbuminemia and
      hypergammaglobulinemia. Skin biopsy revealed amastigotes in phagocytic cells. The
      above findings suggested cutaneous and visceral localization of the leishmania;
      however, the parents absconded with the boy just when treatment was instituted,
      believing that the child was bewitched. The outcome is expected to be fatal
      visceral involvement.

PMID- 21853661
TI  - A rare tumor of nasal bone in a child: osteoblastoma.
AB  - Benign osteoblastoma is an uncommon bone tumor, representing 1% of all benign
      tumors and 3% of all primary bone tumors. Intranasal or paranasal osteoblastoma
      is particularly rare. Osteoblastoma occurs more frequently in males, at a peak
      age between 10 and 20 years. We report an osteoblastoma of the nasal septum in an
      11-year-old boy who presented with swelling of the nasal septum. The diagnosis
      and management of this unusual lesion, as well as the histopathology and imaging
      characteristics, are reviewed. Magnetic resonance imaging (MRI) revealed a solid
      midline nasal mass originating from the septum with intense contrast enhancement.
      There was no evidence of osteoid or chondroid matrix mineralization on computed
      tomography (CT). Biopsy was performed. Histologically, the tumor contained
      abundant plump osteoblast-like cells, with eosinophilic cytoplasm and large
      nuclei that were frequently juxtaposed to the newly formed osteoid. Conservative
      excision was performed. The literature concerning occurrence of osteoblastoma in
      this unusual location is reviewed.

PMID- 21853662
TI  - Hypothyroidism-associated testicular enlargement: is it a form of precocious
      puberty or not? A case report.
AB  - In children with untreated hypothyroidism, the onset of puberty is usually
      delayed, but gonadotropin-independent precocious puberty may occur in children
      with severe hypothyroidism of long duration. The association of hypothyroidism,
      delayed bone age and gonadotropin-independent precocious puberty is defined as
      Van Wyk Grumbach syndrome (VWGS). VWGS has been described mostly in girls, and
      only seldom in boys. The manifestation of VWGS in boys is only testicular
      enlargement without substantial Leydig cell stimulation or testosterone
      secretion. We report a case of testicular enlargement due to obvious
      hypothyroidism secondary to autoimmune thyroiditis in a boy who presented with
      obesity. With this case report, we would like to emphasize that VWGS is not a
      real gonadotropin- independent precocious puberty in boys as it is in girls.
      Additionally, we would like to emphasize that delayed bone age is a special
      discriminating feature for differentiation of VWGS from the other causes of
      precocious puberty.

PMID- 21853663
TI  - Infantile lepromatous leprosy with vulvar localization.
AB  - Reports of leprosy during the first year of life are uncommon. In the early
      diagnosis, the spectrum for most of the children is reported to be largely
      confined to tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB),
      and indeterminate forms of leprosy. We report a one-year-old female infant
      presenting numerous erythematous papules on her labium majus and pale flat
      macules on her chin and right cheek for about four months. A biopsy revealed
      changes typical for lepromatous leprosy (LL). Infantile leprosy and the route of
      transmission are discussed here.

PMID- 21853664
TI  - Primary posterior mediastinal Burkitt lymphoma.
AB  - A 14-year-old boy admitted to our clinic with a 20-day history of fever, cough
      and respiratory distress. Mediastinal enlargement was observed on chest
      radiograph. Computed tomography of the chest demonstrated a large posterior
      mediastinal mass. The histopathological examination of the mass revealed
      Burkitt's lymphoma. We report this case because primary posterior mediastinal
      involvement in Burkitt lymphoma is extremely rare in childhood.

PMID- 21853665
TI  - Hematogones in immune thrombocytopenic purpura: diagnostic implication.
AB  - Hematogones (HGs) are benign immature B cells in bone marrow with a variety of
      benign and malignant conditions, including idiopathic thrombocytopenic purpura,
      leukemia, lymphoma, red blood cell aplasia, iron deficiency anemia,
      amegakaryocytosis, regenerative bone marrow following viral injury, chemotherapy
      or bone marrow transplantation, copper deficiency, autoimmune cytopenias,
      neuroblastoma, and acquired immunodeficiency syndrome (AIDS). HGs may cause
      diagnostic problems because of their morphologic and immunophenotypic
      similarities to neoplastic lymphoblasts. Herein, two patients with
      thrombocytopenia and three lineage dysplasias in the bone marrow suggesting
      myelodysplastic syndrome (MDS) with excess blasts are presented. Light
      microscopic evaluation of marrow from both patients revealed periodic acid-Schiff
      (PAS)-negative blasts However, flow cytometric analysis revealed excessive HGs in
      both patients, implying that the cells that were considered as blasts were
      actually large HGs. Thus, the patients were diagnosed as immune thrombocytopenic
      purpura due to the isolated thrombocytopenia, large platelets on blood and bone
      marrow smears and increased megakaryocytes in the bone marrow. These cases
      emphasize the importance of distinction of hematogone-rich conditions from
      leukemia and MDS for accurate diagnosis and treatment, and the reliability of
      multiparameter flow cytometry for the differential diagnosis.

PMID- 21853666
TI  - Intractable sneezing: is it always psychogenic?
AB  - Intractable sneezing is not a commonly encountered disorder. The clinical
      presentation of such patients may cause the physician to undertake several tests
      before making a diagnosis. Are the performed analytic tests a waste of the health
      service funds or are they really sufficient? In this case, after undergoing
      several tests to rule out potential causes of the prevailing symptoms,
      psychiatric evaluation revealed a triggering event that contributed to the
      diagnosis of psychogenic sneezing. This specific case demonstrates why the
      diagnosis of psychogenic sneezing is difficult. An overwhelming number of such
      patients may be linked to a psychogenic cause; nevertheless, organic lesions or
      causes should be carefully excluded. Addressing the psychosocial issues through
      psychotherapy and coincidental use of locally administered anesthesia assisted in
      resolving the symptoms.

PMID- 21853667
TI  - Localized acute generalized exanthematous pustulosis with amoxicillin and
      clavulanic acid.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a rare skin disorder,
      characterized by acute development of numerous, pin-head sized, nonfollicular
      pustules on erythematous skin, with high fever and neutrophilia. The condition is
      frequently caused by hypersensitivity reaction to drugs or viral infections.
      Diagnosis is established according to clinical and histological criteria. Herein,
      we report a 17-year-old girl with localized AGEP related to the use of
      amoxicillin-clavulanate.

PMID- 21853668
TI  - Convulsion in children with gastroenteritis without severe electrolyte
      disturbance.

PMID- 21853669
TI  - Uveitis: a rare presentation finding of celiac disease in childhood.

PMID- 21853670
TI  - Hemolytic uremic syndrome in a pediatric intensive care unit: a 5-year
      experience.

PMID- 21853671
TI  - [Mobilization and collection of hematopoietic stem cells in children with
      different neoplastic diseases for autotransplantation to support high dose
      chemotherapy (single centre experience)].
AB  - Currently, granulocyte colony stimulating factor (G-CSF) alone or in combination
      with myelosuppresive chemotherapy remain the standards of CD34+ cells
      mobilization allows the safe and successful collection of adequate peripheral
      blood stem cells (PBSC) for autologous transplantation. However, in up to 30% of
      patients mobilization of PBSC is ineffective. This report presents our experience
      in mobilization and collection of peripheral blood stem cells in 82 children with
      different proliferative disease. In mobilization G-CSF was administered alone in
      steady state (56 patients, pts) or in combination with myelosuppresive
      chemotherapy (26 pts). The CD34+ cell count at least 10 cells/ml was required to
      start apheresis procedure, which was repeated, if needed, during following 1-4
      days until collection of at least 2 (optimally 3) x106 CD34+ cells/kg b.w. of
      recipient was obtained. Three pts in each group (3/ 56 and 3/26) failed the first
      course of mobilization. The median number of CD34+ cells mobilized was 4.8 (0.5
      15) x106/kg b.w. The minimal and optimal number of CD34+ cells for
      transplantation was achieved in 85% and 61% of patients in the G-CSF +
      chemotherapy group and in 84% and 54% in the G-CSF group, respectively. The
      efficacy of presented mobilization arms in our group was similar. However, the
      incidence of infection and total hospitalization time during mobilization were
      higher in chemotherapy + G-CSF group.

PMID- 21853672
TI  - [H-oCT1 gene expression as a predictor of major and complete molecular response
      to imatinib of chronic myeloid leukemia. Single center experience].
AB  - Chronic myeloid leukemia is a clonal disorder caused by formation of chimeric
      BCR/ABL gene and bcr/abl protein with abnormally high tyrosine kinase activity.
      The use of imatinib--the first tyrosine kinase inhibitor results in achievement
      of hematologic, cytogenetic and molecular response in majority of patients.
      However despite its high efficacy not all patients respond to imatinib, whereas
      others lose an initial response. Imatinib is a substrate of human organic cation
      transporter-1 (hOCT1), which actively delivers the drug into the cells, and
      efflux transporters. To identify potential imatinib failures, we investigated the
      expression of hOCT1 using real-time quantitative reverse transcription-polymerase
      chain reaction (RQ-PCR) in 155 CML patients. Patients with low pretreatment hOCT1
      expression had inferior major and complete molecular response (MMR and CMR) rates
      (p = 0.0001, p = 0.0001) achieved any time or at 18 months of imatinib treatment
      (p = 0.023, p = 0.022). The expression of hOCT1 is important in determining the
      clinical response to imatinib. The analysis of hOCT1 expression by RQ-PCR is
      convenient and clinically available, and the results could help in introduction
      of optimal first line therapy in CML patients.

PMID- 21853673
TI  - [The characteristics of Gram-positive bacteria isolated from skin lesions
      observed in ambulatory patients and the assessment of their susceptibility to
      antimicrobial drugs].
AB  - The bacterial skin and soft-tissue infections occur commonly and are
      characterized by more or less intensified changes within skin and subcutaneous
      tissue. The bacterial skin infections give rise to significant therapeutic
      problems associated with increasing resistance etiological agents of these
      infections to antibiotics and chemotherapeutics. The aim of this study was to
      assess the distribution of various Gram-positive microorganisms in skin lesion
      observed in ambulatory patients in a period from June 2005 to December 2006.
      There were 116 bacterial strains isolated and identified from clinical samples:
      Staphylococcus aureus, coagulase - negative staphylococi (S.epidermidis, S.
      xylosus, S.capitis, S.saccharolyticus), Propionobacterium acnes, Streptococcus
      spp. (S.agalactiae, S.pyogenes) i Corynebacterium spp. (C. striatum, C.
      amycolatum, C. aquaticum). In the further part of this study we analyzed a
      profile of their susceptibility to antibiotics and chemotherapeutics in relation
      to drugs recommended for the empirical therapy. The resultant resistance patterns
      among the examined bacterial isolates are indicative of certain divergence
      between recommended empirical antibiotic therapy and actual antimicrobial
      susceptibility of many etiologic factors of skin and soft-tissue infections.

PMID- 21853674
TI  - [Frequency of hepatitis B and hepatitis C markers and HIV markers detection in
      blood donors from the Swietokrzyskie region].
AB  - The study analysed the occur frequency of viral hepatitis type B and type C
      markers and HIV markers detected in blood donors from the region Swietokrzyskie
      in the years 2005-2009. In analysed period 78587 blood donors were screened for
      viral markers: 36360 first time donors and 42227 repeat donors. All reactive
      results were confirmed by another test. HBV markers was detected in 0.336% of the
      first time donors and 0.005% of the repeat donors (2 cases of occult HBV
      infection - OBI). HCV markers was detected in 0.597% of the first time donors and
      0.024% of the repeat donors. HIV markers was detected in 0.003% of the first time
      donors and 0.012% of the repeat donors. It was found that the frequency was lower
      than the national average.

PMID- 21853675
TI  - [Comparison of echocardiographic findings in AVS patients with and without high
      IgG, IgM, IgA titers against Chlamydia pneumoniae during 12 months' observation
      of AVS natural course].
AB  - AIM: Comparison of echocardiographic findings in AVS patients with and without
      high IgG, IgM, IgA titers against Chlamydia pneumoniae during 12 months'
      observation of AVS natural course. PATIENTS: 60 AVS patients who did not agree
      for operational treatment were divided into group A (30 patients with high IgG
      titer) group B (30 patients with low IgG titer), group C (22 patients with high
      IgA titer) group D (38 patients with low IgA titer), group E (7 patients with
      high IgM titer), group F (53 patients with low IgA titer) Antibodies titers and
      echocardiographic scans were carried out every 12 months. RESULTS: There were
      more (p < 0.02) patients with AVS deterioration in group A compared to group B.
      Group A patients had lower left ventricle posteriori wall systolic diameter
      compared to group B. There were no differences in echocardiographic parameters
      between group C and D. Mean ejection fraction was lower and mean right atrium
      diameter was higher in group E compared to group F. CONCLUSION: The results may
      suggest link between Chlamydia pneumoniae and deterioration of AVS.

PMID- 21853676
TI  - [Infections in respiratory tract in patents after head injures].
AB  - BACKGROUND: Traumatic brain injury has became one of a very import medical and
      social problem and one of the most serious causes of disability and morbidity. A
      long-term immobility leads to negative cardiovascular, respiratory, metabolic and
      musculoskeletal changes and put the patient at high risk of serious infections.
      Respiratory track infections are after urinary track infections the main cause of
      morbidity. Long-term ventilation and intubation are responsible for a hospital
      acquired pneumonia (HAP). MATERIAL AND METHOD: 398 patients after TBI
      hospitalized in rehabilitation clinic were evaluated taking into account the
      incidence of HAP. The microbiological studies were collected and the most
      frequent pathogen were described. RESULTS: The most frequent pathogen were
      Pseudomonas aeruginosa and Staphylococcus aureus. Patients admitted to the
      rehabilitation clinic were infected with very refractory cultures of bacteria,
      drug resisted. These infections interrupt rehabilitation process and make it
      longer. There are no standards for managing patients after TBI with tracheostomy.
      There is a necessity of creating such standards. CONCLUSIONS: One of the most
      frequent pathogens involved in respiratory tract infections are: Pseudomonas
      aeruginosa and Staphylococcus aureus. Most patients hospitalized at Intensive
      Care Units were in carrier state. These complications extend the rehabilitation
      process and generate high costs. It is necessary to create standards of care of
      patients with tracheostomy after head injury.

PMID- 21853677
TI  - [Assessment of dietary habits in hemodialysis and peritoneal dialysis patients].
AB  - Adherence to a proper diet has a vast impact on the correct course of dialyses,
      wellbeing, and the results of some laboratory investigations in patients with
      declining renal failure. The nutritional status of dialysis patients is closely
      related to food and specific nutrients intake. The aim of study was assessment of
      dietary habits in dialysis patients. The study included 27 patients peritoneal
      dialysis (PD) and 92 hemodialysis (HD). In all of dialysis patients the following
      measurements were taken: body weight and height. The food intake was assessed by
      24-hour dietary recall, (according to nutritional components). The portion size
      was estimated on the "Album of portions of products and dishes". The results were
      compared with dietary recommendations for dialysis patients and analyzed by
      computer software Dietetic 2 designed in the Institute of Food and Nutrition in
      Warsaw but computer program Statistica 7.0 was used for calculations. In all
      studied dialysis patients an irregular diet were observed. The diet was
      characterized by a low energetic value and low intake of proteins, carbohydrates,
      fiber and calcium, as well as by a too high fats. Among women's and man's in both
      groups were noted underweight: (W in PD patients--7%, M in DO patients--8%, W in
      HD patients--4%), overweight (W in PD patients--33%, M in DO patients--25%, W in
      HD patients--38%, M in HD patients--36%) and obesity (W in PD patients--26%, M in
      DO patients--33%, W in HD patients--22%, M in HD patients--21%). The study
      revealed that the daily food rations of peritoneal dialysis women were found to
      have a significantly higher the average intake dietary fiber (18.3 +/- 5.5 g/day)
      and higher potassium intake (2758.5 +/- 787.5 mg/day) as compared to the average
      intake dietary fiber (11.7 +/- 5.4 g/ day; p < 0.0001) and potassium intake
      (1612.9 +/- 822.9 mg/day; p < 0.0001) of hemodialysis women. The regular
      dietician advice is necessary for monitoring of patients nutrition.

PMID- 21853678
TI  - [Liver fibrosis and cirrhosis--causes. Part I].
AB  - Liver fibrosis is one of the most compound pathological process occurred as the
      answer to risen inflammation factor. It is characterized by balance disorders
      between syntesis and degradation ECM (Extracellular Matrix) by myofibroblasts.
      This appears when activated by inflammation factor HSC cells transform in
      myofibroblasts. Among major causes of the chronic liver inflammation, with
      parenchymal cells destruction and replace of connective tissue, are: hepatotropic
      viruses (HCV, HBV), alcohol, autoimmunologic disorders.

PMID- 21853679
TI  - [Liver fibrosis and cirrhosis--selected cytokines, growth factors and proteins.
      Part II].
AB  - Fibrosis is characterized by balance disorders between syntesis and degradation
      ECM (Extracellular Matrix) by myofibroblasts. Activated by inflammation factor
      HSC cells transform in myofibroblasts. This changes are caused and assisted by
      number of mediators: cytokines, growth factors, kinases. All this stimulus we
      call fibrosis factors. This paper compose second part of object-article: Liver
      fibrosis and cirrhosis - causes.

PMID- 21853680
TI  - [Fibroblast growth factor-23 (FGF-23). Part I. Significance in phosphate
      homeostasis and bone metabolism].
AB  - Fibroblast growth factor-23 (FGF-23) discovered in the last years, produced by
      osteocytes and osteoblast is hormone that lowers plasma phosphate level due to
      inhibition of renal tubule phosphate reabsorption (phosphaturic effect). It
      diminishes gut absorption of phosphate as a result of lowered kidney 1alpha
      hydroxylase activity and respective decreased active vitamin D1,25(OH)2D
      synthesis. FGF-23 acts in the presence of the co-receptor Klotho protein which
      stabilizes its binding with receptor. The pathological states that are associated
      with increased FGF-23 synthesis in normal renal function lead to
      hypophosphatemia, while its deficiency may lead to severe hyperphosphatemia. The
      increased FGF-23 synthesis in patients with chronic kidney disease (CKD) allow to
      maintain phosphate concentration in spite of severe kidney dysfunction. This
      problem will be discussed in the II-nd part of this review.

PMID- 21853681
TI  - [Still's disease or systemic lupus erythematosus in a young adult patient-
      diagnostic doubts].
AB  - Systemic lupus erythematosus and Still's disease are chronic autoimmune disorders
      of unknown etiology. Symptomatology of these diseases may be similar causing
      diagnostic difficulties. Long-term observation and immunological studies are
      essential to identify the definite disorder. We present a case of a 24-year-old
      patient with high fever, sore throat and arthritis. During hospitalization rash
      accompanying fever, nodular erythema, pulmonary changes, liver damage and
      splenomegaly were observed. Although initially adult-onset Still's disease was
      diagnosed according to the Yamaguchi criteria, the diagnosis of systemic lupus
      erythematosus was made after re-analysis of the clinical course and immunological
      tests.

PMID- 21853682
TI  - Write to your MP about ENs.

PMID- 21853683
TI  - Workforce reform.

PMID- 21853684
TI  - Public opinion and ethics.

PMID- 21853685
TI  - Workplace aggression and violence: nurses and midwives say NO.

PMID- 21853686
TI  - Case study: the emergency nurse practitioner caring for the patient with a
      urinary tract infection.
AB  - Patients presenting to the Emergency Department (ED) with a Urinary Tract
      Infection (UTI) is a common occurrence and one of the patient categories that the
      Emergency Nurse Practitioner (ENP) treats. This article provides a review and
      case study of a patient presenting to the ED with a UTI and how she was assessed
      and managed clinically.

PMID- 21853687
TI  - Boosting capacity of emergency clinicians.

PMID- 21853688
TI  - Helping a hidden population.

PMID- 21853689
TI  - Working with the mob.

PMID- 21853690
TI  - Transfer from high dose methadone to buprenorphine/naloxone.

PMID- 21853691
TI  - The wait on the nurses' shoulders.

PMID- 21853692
TI  - May Day: a chance to celebrate a proud union history.

PMID- 21853693
TI  - Teenagers: transition to parenthood.

PMID- 21853694
TI  - Evaluating the family nurse partnership in England: the Building Blocks trial.
AB  - The Family Nurse Partnership (FNP) Programme is a structured intensive home
      visiting programme delivered by trained family nurses to nulliparous teenagers
      throughout pregnancy and until their child is two years old. Currently FNP is
      provided in over 60 primary healthcare sites in England with a planned capacity
      increase to 13,000 concurrent clients by 2015. Researchers from the South East
      Wales Trials Unit at Cardiff University are testing the effectiveness of FNP in
      England in the Building Blocks study--a randomised controlled trial funded by the
      Department of Health (DH). The trial team includes collaborators from the
      Universities of York, Bristol and Glamorgan.

PMID- 21853695
TI  - Birth trauma.

PMID- 21853696
TI  - The other side.
AB  - Gemma had just returned to labour ward for her second year placement, her
      previous labour ward placements having been on a midwife-led unit. The consultant
      led unit was a busy place dealing with much more problematic deliveries, none of
      which Gemma had experienced before. She was involved in the case of a teenager
      presenting to labour ward, in labour, from community. There was some concern over
      the well-being of the baby and on arrival it was confirmed he had died. Gemma
      wanted to reflect on this, but found it difficult to do so. Instead, she writes
      below a post she made on the university's Blackboard site, asking for a boost
      from her fellow student midwives and some perspective on being a student midwife.

PMID- 21853697
TI  - Go folic!
AB  - Go Folic! is a major new campaign aimed at getting any woman who might become
      pregnant to take the right amount of folic acid at the right time. In order to
      prevent neural tube defects (NTDs), and proactively prevent new cases of spina
      bifida and hydrocephalus, it is essential that women take folic acid well before
      becoming pregnant. Through the use of social networks, and the voice of
      healthcare professionals, it is hoped that more women than ever before will
      receive the Go Folic! message and start taking the 400mcg/day required to ensure
      the development of a healthy brain and spine.

PMID- 21853698
TI  - Young, pregnant and in need of support.
AB  - This is an interview with a young parent about her experience of being pregnant
      at 17. NICE released their guidelines in October 2010 to recommend a flexible
      model of tailored antenatal care for young parents. Prior to this Bath had set up
      a Young Parents' One Stop Shop offering antenatal provision in the form of
      antenatal classes, antenatal appointments at the same location and a range of
      other services to be accessed at the same time. Anita wanted a first hand account
      of a young mother's thoughts and feelings during pregnancy and whether they were
      in line with the recommendations of NICE.

PMID- 21853699
TI  - Why young dads matter...and how to reach them.
AB  - Most maternity services address themselves squarely to mothers, but evidence
      suggests that engaging with fathers can be an important way of achieving better
      outcomes, both for children and their mothers. This article debunks some of the
      commonly heard myths about young fathers (for example that they are not 'around'
      or interested in fatherhood), summarises key aspects of their importance and
      suggests approaches which maternity professionals might find useful when trying
      to engage with them.

PMID- 21853700
TI  - The fitness to practise hearing. 2. Keep calm and carry on: appearing at a
      hearing.
AB  - Solicitor, Mark Solon, gives practical advice on appearing at a Fitness to
      Practise hearing. Giving evidence can be a daunting prospect for midwives whose
      professional future can be at stake. They need to have good written evidence to
      rely on as well as understanding the process.

PMID- 21853701
TI  - Research midwives: look at the evidence!
AB  - Evidence based practice underpins modern healthcare and includes the use of
      research knowledge, consideration of an individual's circumstances and their
      personal preferences. Maternal and child health care interventions aim to prevent
      disease and disability and promote health and wellbeing. Before interventions are
      brought into practice the benefits and risks should be adequately evaluated to
      ensure clinicians and those receiving the interventions fully understand the
      potential effects. A multidisciplinary team approach to the development of
      research initiatives is advantageous. The team should include clinicians,
      researchers and service users working together to answer important clinical
      questions. It is our view that clinical research midwives are pivotal to the
      success of maternal and child health improvement initiatives. For example they
      can help reduce the gap between clinical practice and research by making research
      understandable to clinicians and applicable to practice by working in partnership
      with academics.

PMID- 21853702
TI  - Learner evaluation including design, use and evaluation of an appropriate tool.

PMID- 21853703
TI  - Using historical research to make sense of our past, our present and our future.
      4. History in context and disseminating findings.
AB  - This is the last in a series of four pieces looking at the use of historical
      research to explore midwifery. This final part looks at how historical findings
      can be placed in a theoretical framework and how they may be disseminated.
      History can shed new light on contemporary research projects as well as being
      fascinating in its own right, and can be used not just for academic work but to
      tell the story of people and places connected with our profession.

PMID- 21853704
TI  - Is there a need for education on the indication for episiotomy?

PMID- 21853706
TI  - Mind your language!

PMID- 21853707
TI  - Reflections on reflective practice.

PMID- 21853705
TI  - Conference preview: Interview with Detective Chief Superintendent John Carnochan.
AB  - This year's UNICEF Baby Friendly Conference in November will be as diverse as
      ever, with speakers touching on all aspects of infant feeding and care for new
      mothers and their babies. One speaker will be Detective Chief Superintendent John
      Carnochan, Head of the Scottish Violence Reduction Unit. Nearly four decades in
      the police force have taught John that early years intervention and support for
      vulnerable mothers, in particular, are at the heart of violence reduction, and
      that to reduce homicide rates we must invest resources in health professionals to
      support the early years.

PMID- 21853708
TI  - Our calling: loving God in nursing (Part 1).

PMID- 21853709
TI  - Privileged trust.

PMID- 21853710
TI  - Reintroducing the pinning ceremony.

PMID- 21853711
TI  - Warm glow.

PMID- 21853712
TI  - The power of our words.

PMID- 21853713
TI  - Reflective practice for personal and professional transformation.
AB  - Reflection is the mindful (and prayerful) consideration of professional or
      personal actions in such a way as to transform present and future experience.
      Nurses will find ways to create transformation in patient care through reflection
      in practice, clinical supervision, leadership, education, and evidence-based
      practice. This article discusses models and processes for reflective practice for
      professional, personal, and Christian spiritual transformation, making
      application to case studies in nursing practice.

PMID- 21853714
TI  - Living out reflective practice.
AB  - Nurses are being encouraged to be reflective practitioners, but what does that
      mean? This article describes reflection-in-action and reflection-on-action, and
      offers practical advice on how to reflect critically in day-to-day practice and
      life. A comparison is made between professional reflective practice and biblical
      reflection or meditation.

PMID- 21853715
TI  - Are parish nurses prepared to incorporate the spiritual dimension into practice?
AB  - This qualitative study assessed if parish nurses (PNs) perceive the basic
      preparation course they attended prepared them to incorporate the spiritual
      dimension into their practice. It was unclear if the course was a major variable
      or if previous spiritual training and experience are the critical dimensions
      related to whether or not PNs feel prepared to incorporate the spiritual
      dimension into their practice.

PMID- 21853716
TI  - Challenges and trends in global healthcare missions.
AB  - Changes in travel, communications, and technology are impacting how the ministry
      of healthcare missions is being implemented around the globe. This article
      discusses five emerging trends in healthcare missions, offering rationale for
      each and a vision for bringing health and healing among all peoples of the world.

PMID- 21853717
TI  - What is a Christian faith-based recovery program?
AB  - No descriptions of faith-based recovery programs (FBRPs) that include explicit
      religious content and activities were found searching 2004-2010 electronic
      databases. This article describes an underdocumented FBRP: an evangelical
      Christian faith-based recovery home (FBRH) known as The Potters House Restoration
      Ministries, to increase awareness about a FBRP that incorporates explicitly
      religious components, and reiterates the call for better description of FBRPs so
      that replication and evaluation of outcomes are possible.

PMID- 21853718
TI  - American African women and smoking: spiritual well-being makes a difference.
AB  - This study examined relationships among spiritual well-being (SWB), perceived
      stress, coping, and smoking in African American (AA) women. Significant
      relationships were found among participants related to SWB, regardless of smoking
      status. SWB may provide a protective property against stress and the desire to
      smoke. Results support inclusion of SWB into health and smoking education,
      support of the AA faith community, and the use of SWB as a component of the
      healthcare decision-making process.

PMID- 21853719
TI  - Back to school: what I learned teaching cross-culturally.
AB  - The need for nurse educators around the globe is prompting some to do short-term
      teaching internationally. Prompted by God's call and the great need at the
      Faculty of Nursing Science of the Episcopal University of Haiti (FSIL), the
      author taught in Leogane, Haiti, for 18 days. This article shares practical
      insights from her experience and important revelations about teaching cross
      culturally.

PMID- 21853720
TI  - What is the essence of spiritual care?

PMID- 21853721
TI  - Letting go with peace.

PMID- 21853722
TI  - Reducing rates of catheter-associated urinary tract infection.

PMID- 21853723
TI  - Achieving quality care at end of life.

PMID- 21853724
TI  - Chemical policy reform--nurses must say "Yes".

PMID- 21853725
TI  - [Don't forget the occupational environment in the sick listing debate].

PMID- 21853726
TI  - [The relation between the insurance authority and the medical profession. We have
      to take the consequences now].

PMID- 21853727
TI  - [EHEC is a still current and potent bacteria. More outbreaks coming--complete
      preparedness is required].

PMID- 21853728
TI  - [Snuff during pregnancy no risk-free alternative to smoking].

PMID- 21853729
TI  - [Fasting during Ramadan possible for some persons with diabetes--but not all.
      Increased risks with fasting during summer time--competent counseling is
      necessary].

PMID- 21853730
TI  - [EHEC can cause serious intestinal infection also in adults. A seriously ill 56
      year old woman--developed life-threatening complications].

PMID- 21853731
TI  - [TBE in an elderly vaccinated couple. Don't forget booster doses to the
      elderly!].

PMID- 21853732
TI  - [The National Board of Health and Welfare's policy on subdivision of medical
      specialties: when, how and why].

PMID- 21853733
TI  - [Always investigate first onset thunderclap headache].

PMID- 21853734
TI  - [Pancreatoduodenectomy--past, present and future].
AB  - Pancreatico-duodenectomy represents one of the most important and complex
      surgical digestive procedure. Although rarely performed in the past, nowadays has
      become a routine surgery. Moreover, postoperative mortality significantly
      decreased (from over 30% to less than 5%), while the number of severe, life
      threatening complications were reduced. This outcome was possible due to
      technical innovations acquired in time, and also due to a better per operative
      management of these patients, in tertiary surgical centers, with experienced
      operative teams. Some modifications of the standard procedure of resection, like
      posterior or artery first approach contributed to better results, facilitating en
      block resection of the portal/ superior mesenteric vein, where needed. Moreover,
      posterior approach facilitates complete mesopancreas excision, involved in local
      recurrence after resection of pancreatic head adenocarcinoma. Regarding
      reconstruction after pancreaticoduodenectomy, there is no optimal type of
      anastomosis (pancreatico-gastrostomy vs pancreatico-jejunostomy), results being
      related mostly with the expertise of the operative team, as like the
      postoperative pancreatic fistula rate. Future studies are deemed to look on the
      real clinical impact of the total mesopancreas excision in achieving negative
      resection margins, decreasing local recurrence and increasing the long-term
      survival of patients resected for pancreatic head cancer.

PMID- 21853735
TI  - [Current problems in surgical oncology. Part 3. Total mesorectal excision with
      curative intent. Why are not all patients with rectal cancer treated with
      minimally invasive procedures (either by laparoscopy or by robotic surgery)?].
AB  - The main evaluation criterion in rectum cancer surgery is the accuracy of total
      mesorectal excision (TME). Laparoscopic TME has some advantages (sharp
      dissection, a better visibility) over open surgery; there are other factors that
      limited the dissemination of the laparoscopic approach (rigid instruments, with a
      limited maneuverability). Laparoscopic TME can be beneficial for selected
      patients. Robotic surgery, with a better view and instrument versatility, may
      overcome in part the limitations of laparoscopic TME. The excellent results
      demonstrated by robotic surgery in other types of pelvic malignancies (in urology
      and gynecology) are expected in the treatment of rectum cancer surgery. However,
      still remain patients with advanced rectum cancers that can be operated correctly
      only by open surgery. Laparoscopy and robotics are only tools and not aims of the
      oncological surgery.

PMID- 21853736
TI  - [Latest approaches in the surgical treatment of cutaneous malignant melanoma].
AB  - Malignant melanoma is a disease with an unpredictable evolution. Detected in
      stage I and II has a great chance to cure, if it is correctly treated: excisional
      biopsy with safety margins in accordance with tumor thickness. Lymphoscintigraphy
      with sentinel node identification and biopsy became compulsory for staging
      malignant melanoma, the role of complete lymphadenectomy would be established by
      publishing the MSLTII data. The sentinel node is analysed using more and more
      sophisticated techniques (RT-PCR) in order to detect isolated tumoral cells,
      although their clinical significance is not known yet. Metastases occurrence is a
      dramatic phenomenon because chemotherapy, radiotherapy or biologic therapy have
      insignificant results. The only therapeutic modality which may increase survival
      in this situation is surgery for some carefully selected patients.

PMID- 21853737
TI  - [Posterior fossa epidural hematoma].
AB  - Posterior fossa epidural hematomas (PFEH) are rare entities, with dark prognosis
      due to their specific localization. Because the simptomatology is usually
      nonspecific or poor, the CT should be performed as soon as posible. MRI does not
      offer suplimentary benefits/informations in the great majority of PFEH. Depending
      on the bleeding source, the rate of clinical signs appearance and the gravity of
      evolution varies. Early diagnosis and surgical treatment should be performed in
      hematomas associated with mass effect or suplimentary injuries. In all cases, in
      PFEH patients a careful monitoring is necessary due to unpredictable evolution
      and rapid clinical worsening, requiring surgical intervention.

PMID- 21853738
TI  - Laparoscopic adrenalectomy for large solid cortical tumours--is it appropriate?
AB  - BACKGROUND: Laparoscopic adrenalectomy, the procedure of choice for small benign
      adrenal tumours, is also used for large tumours. Our study aims to assess the
      outcome of large adrenal tumours laparoscopically resected. METHODS: All patients
      with laparoscopic adrenalectomy performed in between 2002 and 2009, without
      preoperative or intraoperative malignant characteristics, were reviewed.
      Clinical, biochemical and CT follow-up data were reviewed for evidence of
      recurrent disease. RESULTS: Fifty patients underwent laparoscopic adrenalectomies
      in our unit, 18 of them having solid cortical tumours > or = 7 cm without
      preoperative or intraoperative malignant features: 6 Cushing's syndrome tumours,
      8 non-secreting tumours, 4 aldosteronomas. The mean age of the patients was 46.89
      years (range 22-64 years), and the mean tumour size 7.57 cm (range 7-9.1 cm).
      Histology identified 10 cortical adenomas, 4 malignant tumours, and 4
      indeterminate tumours. The mean - follow-up was 28.94 months (range 4-58 months).
      Three patients died of systemic recurrent disease (liver and lung metastases) at
      12, 19 and 21 month, respectively, after operation. One patient underwent a left
      hepatectomy for liver metastases, 33 months postoperatively. Fourteen patients
      have no evidence of recurrence. CONCLUSIONS: Adrenal tumours > or = 7 cm without
      pre- or intraoperative evidence of malignancy are resectable laparoscopically.
      This approach is unlikely to worsen the long-term outcome. The mortality is
      related to the malignancy.

PMID- 21853739
TI  - [Non-ulcerous duodenal perforations: a clinical analysis of 23 cases].
AB  - Non-ulcerous duodenal perforations are a rare and seldom studied pathology. The
      present retrospective study analyses a group of 23 patients, over a 10 year
      period (Jan 1st 2000 - Dec 31st 2009) with this pathology. The most frequent
      etiology was iatrogenic (52.17 % after ERCP and 17.39% after upper
      gastrointestinal endoscopy). Other rare etiologies included were tumoral
      perforations, penetrating wounds, and ingestion of foreign bodies. The lesions
      vary from millimetric perforations to total necrosis of the wall of a duodenal
      segment and are often associated with other complex lesions. The overall
      mortality was 52.17%, a little lower for the post ERCP injuries (40%). Usually
      the iatrogenic lesions are diagnosed earlier (ex. 54.54% of the post ERCP lesions
      undergo surgery during the first 24 h), probably increasing the chance of
      surviving. 43.47% of cases undergo surgery in the condition of severe sepsis,
      with multiple organ failure, thus aggravating the prognosis. Sometimes the
      patient required multiple interventions (with a maximum of 8 in our group). In
      26% of the cases the primary intervention was just paraduodenal and/or
      retroperitoneal drainage, suture of the duodenum (6 cases - 26%), usually under
      the protection of a gastro-enteroanastomosis (4 cases - 17.39%), suture of the
      duodenum around a decompression tube (26%), sometimes suture of the duodenum with
      a jejunal serous patch or duodeno-jejunal anastomosis. The bile drainage and the
      jejunostomy were associated sometimes. The procedures in this pathology have a
      significant morbidity, with a high rate of reinterventions (30.4%).

PMID- 21853741
TI  - [Results and prognostic factors in rectal cancer surgically treated with curative
      intent--experience of a single tertiary center].
AB  - BACKGROUND: Rectal cancer has a paradoxal prognosis in about 25% of patients,
      although intraoperative parameters and tumor stage are known as major
      determinants of prognosis. AIM: This study assessed the prognostic factors in
      patients with rectal cancer treated without total mesorectal excision in long
      term follow-up. MATERIAL AND METHODS: A single center tertiary population
      included retrospectively 87 patients with rectal cancer operated between 1992 and
      2002 using conventional resection. Some 90.5 per cent of the patients had surgery
      alone and 9.5 per cent had postoperative radiochemotherapy. Patients who did not
      have adenocarcinoma, those in whom the curative operation was not done, and those
      who received preoperative radiotherapy were excluded. Median follow-up was 7
      years. RESULTS: Seven-year cancer specific survival was 52% (95% CI:3.21) and
      only pT, pN and lymphatic invasion were significant as prognostic factors on
      multivariate analysis. Disease free cancer survival was 56% and only lymphatic
      invasion was significant for prognosis. The risk of death was higher for abdomino
      perineal resection (APR) than for anterior resection (AR), advanced pT stage,
      vascular and perineural invasion. Local recurrence and distant metastasis were
      12.6 and 26.43 per cent respectively for patients. The risk for local reccurence
      was higher for advanced pT stage, perineural and lymphatic invasion and distal
      margin invasion. The risk for metastasis was higher for advanced pT stage and
      vascular invasion. CONCLUSION: Advanced tumor stage and lymphatic invasion
      represent prognostic factors in rectal cancer, suggesting the necessity of
      adjuvant therapy in cases with lymphatic invasion.

PMID- 21853740
TI  - [Particular aspects of endoprosthesis in malignant advanced pharingeal-esophageal
      stenosis].
AB  - INTRODUCTION: The esophageal neoplasm is currently the seventh cause of death
      through cancer worlwide. In the developing countries it is situated on the fifth
      place and has one of the worst prognostics for a neoplasm. Due to the specifical
      intratoracical topography, clinically inaccesible and without symptoms, the
      disease is rather incurable when the disphagia appears. MATERIAL AND METHOD: The
      esophageal prosthesis procedure through laparogastroscopical approach, used by
      us, is an original one, noninvasive, acknowledged both nationally and
      internationally. The endoprosthesis esophageal cases belong to three Clinics of
      Surgery (Clinic Surgery 2 from Sibiu, Clinic Surgery 1 from Braila, Clinic of
      Surgery 4, Bucharest) on a period of 14 years (1996-2009), identically
      coordinated. RESULTS AND DISCUSSIONS: Out of the 68 patients, 18 cases have been
      cancers situated in the medial and inferior third and 28 have been eso-cardial
      tuberositary neoplasms. In the cases of the high malignant pharingeal-esophageal
      stenosis, the placement of the prosthesis (different prosthesis adapted to this
      particular situation) in areas of aerial-digestive junction implies significant
      technical difficulties especially in the option with the conservation of the
      larinx as a fonatory and respiratory solution. CONCLUSIONS: Our original
      procedure, simple and efficient presents numerous advantages which allow the
      widening of the indications of stent gastroenterology: firm traction, the
      possibility of catheterism through narrow lumens of 1-2 mm, sometimes
      anfractuous, the distal visibility, the visual placement or expanding of the
      prosthesis, the evaluation of the intraoperatory visceral or parietal methastasis
      and eventually the avoidance of the gastrostomic invalidation.

PMID- 21853742
TI  - [Improvement in the quality of life for patients with adjustable gastric banding:
      initial results].
AB  - The aim of the study was to evaluate the improvement in quality of life for
      patients that have undergone the laparoscopic gastric banding, using the BAROS
      and Moorehead-Ardelt II questionnaires. METHODS: We selected a 20 patient group
      (65% women) that underwent this surgical procedure in our clinic. The initial
      average weight was 123.45kg, and the body-mass index of 42.36. The average age
      was 29.25 years. The pars flaccida technique was used in 18, and the perigastric
      approach in 2 cases. RESULTS: No complications or intraoperative accidents
      occurred. The mean operation time was 115.5 minutes. Elective conversion was
      needed in one case with a BMI of 55. The average hospital stay was of 3.2 days.
      The follow-up was conducted at least through phone in 95% of cases, and its
      average duration was of 10 months. The only postoperative complications were
      infections of the subcutaneous port (5 cases - 25%) which needed removal of the
      port, but not of the banding. The average loss of excess weight was 48.23%. Using
      the BAROS score to determine the overall improvement of quality of life, 30% of
      the patients scored as "Very Good", 50% as "Good", 20% as "Fair". Using the
      Moorehead-Ardelt QLQ II score, 65% scored as "Very Good", 30% as "Good" and 5% as
      "Fair". CONCLUSION: The laparoscopic adjustable gastric banding significantly
      improves the quality of life for most patients with this procedure.

PMID- 21853743
TI  - Pathological evidence in support of total mesorectal excision in the management
      of rectal cancer.
AB  - BACKGROUND: Pelvic recurrence following conventional rectal resection for cancer
      is common. Preoperative iradiation has been shown in prospective randomized
      studies to halve this risk. AIM: This multiinstitutional study aimed to assess
      the necesity of total mesorectal excision in rectal cancer. PATIENTS AND METHOD:
      Pathological resections from 50 consecutive patients with adenocarcinoma of the
      rectum within 12 cm of the anal verge who underwent currative resection
      incorporating total mesorectal excision were examined. The resection specimen was
      examined by one of two pathologists. Some 50 total mesorectal excision specimens
      were examined following rectal excision for cancer. Some 38 had total mesorectal
      excision as a component of a low anterior resection and 12 with abdomino-perineal
      resection. "Cure" was defined as absence of metastatic disease and the excision
      of entire macroscopic tumor tissue with negative proximal and distal borders. TME
      was performed as described by Heald et al. The mesorectum was evaluated for lymph
      nodes and tumor deposists in three areas: deep to the tumor, in the proximal
      mesorectum and in the distal mesorectum. RESULTS: Six patients had Dukes A
      lesions. Of 21 patients with Dukes B tumors, five had discrete foci of
      adenocarcinoma in the mesorectum, with no evidence of lymph node metastasis.
      Dukes C lesions were more heterogeneous, but 12 out of 23 patients had distinct
      mesorectal deposists in addition to mesorectal node involvement. Circumferential
      margin involvement was rare, but mesorectal tumor deposits were present in 17 of
      44 patients with pT3 tumors, and 23 of 44 had mesorectal nodal involvement. No
      patient with a pT2 tumor had mesorectal involvement. Failure to excise the
      mesorectum completely has the potential to leave gross or microscopic residual
      disease that may in theory predispose to local failure. CONCLUSION: Total
      mesorectal excision is necessary to avoid incomplete pathological evaluation of
      the mesorectum and understaging of rectal cancer.

PMID- 21853744
TI  - [Laparoscopic ultrasound in biliary diseases].
AB  - Laparoscopic ultrasound is an intraoperative exploration of the abdominal viscera
      using ultrasounds. The aim of this work is to obviate this new method of
      exploration and to underline its advantages and limits. In this study were
      enroled 65 pacients with gallbladder stones, admitted in The Surgical Clinic,
      "Elias" Emergency Hospital, from October 2005 until December 2006. The measured
      parameters were CBD size and the presence of stones or sludge within CBD, and
      various methods were compared: abdominal ultrasound, laparoscopic ultrasound and
      laparoscopic cholangiography. The results allowed us to consider that
      laparoscopic ultrasound is a useful tool for the intraoperative diagnosis of
      choledocolithiasis. When compared to laparoscopic cholangiography, our study
      revealed the same specificity and positive predictive value, and a sensitivity of
      0.93.

PMID- 21853745
TI  - [Septic metastases of suppuration of odontogenic origin].
AB  - The infections of odontogenic origin, set in the soft tissues region of the
      viscerocranium are among the most frequent conditions specific to this anatomical
      level. A distinct category among these, represented by the conditions with
      diffuse character, may have serious forms, developing systemic septic metastases.
      The current paper displays a study approaching seven cases of odontogenic diffuse
      infections with metastases at distance. The ways in which the septic metastases
      appeared, as well as the topic and general prescribed treatment have been
      analyzed. The expanding at distance of the suppuration occurred at those patients
      who were suffering from cervical necroziting fasciitis associated to some
      immunodepressing conditions. Out of the 7 patients involved in the study, 4 were
      suffering from uncompensated diabetes and obesity. All those 7 patients had
      septic conditions localized in mediastinal region, and in 3 cases hepatic septic
      affections were observed. The best treatment possible for these conditions proved
      to be the surgical one associated with that concerned with the sustenance of the
      general state of health, the rebalancing of the homeostatic constants and the
      antibacterial one. The post-surgical evolution in case of 5 patients was a good
      one, in case of 2 patients being unfavourable because of the appearance of the
      multiorganic insufficiency and of death.

PMID- 21853746
TI  - [Laparoscopy-assisted total vaginal hysterectomy with transperitoneal
      lymphadenectomy for early cervical cancer--surgical technique].
AB  - Cervical carcinoma remains an important health problem. The classical surgical
      approach for cervical cancer is radical hysterectomy (Wertheim's operation). Our
      paper presents the technique of laparoscopic assisted radical vaginal
      hysterectomy with transperitoneal lymphadenectomy, as well as the details for the
      dissection of obturator, paravesical, pararectal fossae, and parametrectomy. The
      major advantage of this techique is that the entire abdominal part of the
      procedure is performed under direct observation, therefore minimizing the
      visceral or vascular injury. CONCLUSION: Our experiences suggest that this type
      of approach is feasible and offers the possibility to remove a greather number of
      lymph-node as compared to the classical approach. An increased experince will
      prove helpful in performing the entire procedure laparoscopically.

PMID- 21853747
TI  - [Gunshot wound to the root of the neck; bullet on the cervical pleura; operation;
      recovery, 1937].

PMID- 21853748
TI  - Double suturless hepaticojejunostomy.
AB  - In iatrogenic lesions of the main bile duct, especially when the injury is above
      the level of the hepatic bifurcation, the surgeon ought to use two short and thin
      biliary stumps. It is necessary to perform separate anastomoses, using a "Y loop"
      and creating a double hepaticojejunostomy. Technical difficulties increase when
      the biliary ducts are thinner, tighter and separated from one another for a
      distance more than 2 cm. In such case we have attempted to develop a double
      sutureless hepaticojejunostomy by simply keeping the bilioenteric partners in
      apposition with continuous traction exerted via the biliary stents.

PMID- 21853749
TI  - [Gastric metastasis of clear cell renal carcinoma].
AB  - We report the case of a patient operated in 2003 for renal clear cell carcinoma
      (CCRC), when left nephrectomy was performed. In the years following occur: lung
      (2004) and brain (2006) metastasis, pathological bone fracture in right femur
      (2007), which needed a complex treatment: polichimiotherapy, cobaltotherapy,
      right temporal metastasectomy, right femoral fixation with metal rod. In our
      clinic was hospitalised for serious upper gastrointestinal bleeding, severe
      anaemia (haemoglobin 5.8 g%, hematocrit 18.3%) produced by a ulcerated gastric
      metastasis. The inefficiency of medical treatment, patient and family desire to
      operate, have led us to practise Pean type gastrectomy necessary for palliative
      role (raising the hemorrhagic metastasis). Scarcity of the gastric metastasising
      of CCRC are discussed and also the surgical indication in the context of a
      plurimetastatic patient.

PMID- 21853750
TI  - [Clinical and morphological features in a case of recent gastric carcinoma (the
      signet ring cell carcinoma type)].
AB  - The article presents the case of a male patient, hospitalized due to severe pain
      in the upper abdomen area, nausea, and vomiting. The patient was diagnosed with
      surgical acute abdomen, for which emergency surgery is performed. Upon
      penetration into the peritoneal cavity, stomach inspection shows at the medio
      gastric level, on the greater curvature, a callous gastric ulcer, with a central
      perforation. A large excision is decided up to the healthy (normal) gastric
      tissue, and the resulting pieces are sent to the pathological anatomy laboratory.
      The histopathological exam reveals signet ring cell recent gastric carcinoma. The
      biopsy performed 1 month after surgery, prelevated from the antropyloric zone,
      reveals antropyloric gastritis with moderate activity and Helicobacter pylori
      positive. Due to the fact that such cases when this gastric cancer type is
      diagnosed in recent stages are extremely rare, we considered it useful to present
      it and look into its macroscopic and microscopic aspects, as well as into the
      differentiating diagnosis.

PMID- 21853751
TI  - Pancreatic true cysts--diagnosis and treatment difficulties.
AB  - Pancreatic true cysts represent a rare, heterogeneous group of pancreatic tumors;
      therapeutic strategy is based on patient's general status, cyst topography, and
      especially the estimated risk of malignancy. This paper aim is to present 7 cases
      of pancreatic true cysts, operated on a six years period (January 2004-January
      2010) in our surgical clinic: 2 men and 5 women, aged between 24-61 years old;
      cyst diameter varies between 3.5-15 cm, tumor location being pancreatic head in
      two cases and the distal pancreas in 5 cases. Surgical treatment consisted in
      cyst enucleation (two cases), splenopancreatectomy (three cases),
      duodenopancreatectomy (one case), and subtotal splenopancreatectomy (one case).
      Histology was represented by serous cystadenoma (one case), mucinous cystadenoma
      (2 cases), intraductal papillary mucinous cystadenoma (one case), and papillary
      cystadenocarcinoma (3 cases).Postoperative results were good in all cases, with 3
      postoperative pancreatic external fistulas, resolved conservatory; no case of
      post-pancreatectomy diabetes mellitus was registered. In conclusion, surgical
      removal of the pancreatic cystic tumors is necessary, especially due to the risk
      of malignancy, at least in the absence of rigorous histological proofs of
      benignancy. Postoperative results are favorable in terms of postoperative
      morbidity and mortality.

PMID- 21853752
TI  - [Budd-Chiari syndrome--case presentation].
AB  - The Budd-Chiari syndrome represents the obstruction of hepatic veins usually due
      to a hepatocarcinoma. We present the case of a 68 year old patient, in medical
      evidence for ten years with a Child A ethanolic liver cirrhosis, who was admitted
      in emergency for hematemesis and melena. Clinical examination and the laboratory
      findings at the admittance revealed signs of decompensated cirrhosis and severe
      anemia. Ultrasound examination showed a cirrhotic liver with portal hypertension
      signs and a multinodular mass in the right lobe of the liver with portal, biliary
      and right hepatic vein invasions extended to inferior caval vein. In upper
      digestive endoscopy stage IV esophageal varices were evidenced with signs of
      recent bleeding (sclerotherapy was performed) along with gastric varices and
      portal gastropathy. The particularity of the case consists in the invasive
      complications of the hepatocarcinoma regarding hepatic and inferior caval veins
      wich defines the Budd-Chiari syndrome (posthepatic portal hypertension added to
      the intrahepatic and prehepatic ones), the invasions of the biliary tract and
      portal vein being more frequent.

PMID- 21853753
TI  - Complex anatomical variant of inferior vena cava--a case study.
AB  - This case has multiple anatomical variants of the inferior vena cava and its
      branches which determine the appearance of associated arterial abnormalities. The
      study has been performed on a female corpse, aged average 60, with no other
      morphological changes of the blood vessels or retroperitoneal viscera. The method
      we used was classical dissection. We described a variant of the inferior vena
      cava formation and persistence of bilateral double renal arteries with changes of
      arterio-venous relations in the renal pedicles. We established correlations
      between the embryological development of the inferior vena cava and the renal
      vessels and we explained its appearance mechanisms. The peculiar aspect of the
      study is that anomalies in development of the inferior vena cava system have
      determined the disturbance of successive development of renal arteries during
      "ascensus renis" process. We consider important for the surgeon to have knowledge
      of possible anatomical variants of large retroperitoneal vessels in order to have
      a clear interpretation of the CT Angiography and Magnetic Resonance Angiography
      in such cases.

PMID- 21853754
TI  - [Emergency pancreatoduodenectomy for severe iatrogenic duodenal injury--case
      report].
AB  - We present the case of a male patient admitted for high flow biliary fistula (>
      2000 ml/24h) as a consequence of a prior right nephrectomy by lumbar approach.
      The patient was operated after the failure of the medical conservative treatment
      and continous declining medical status. We noted the complete absence of the
      gastric antrum, duodenum I and II with the intraperitomeal direct display and
      opening of the Vater papilla, witch was difficult to identify unless common bile
      duct (CBD) was catheterized by supraduodenal choledocotomy. We performed
      emergency pancreatoduodenectomy with a good postoperative outcome , excepting a
      residual postnephrectomy abscess, witch was consequently evacuated and drained.
      The patient left the clinic 28 days postoperatively. The two years after follow
      up notes that the patient is in a good condition

PMID- 21853755
TI  - Emergency pancreaticoduodenectomy in a patient with an ampullary adenocarcinoma
      associated with severe acute pancreatitis: a case report.
AB  - Emergency pancreatico-duodenectomy is an infrequent surgical procedure. Herein,
      it is reported the case of a 58-year old man with ampullary carcinoma revealed by
      acute necrotizing pancreatitis. Due to clinical features, an emergency two-step
      pancreatico-duodenectomy was performed, accomplished by pancreatic and
      peripancreatic necrosectomy. The distal remnant pancreas was drained as an
      external pancreatic fistula. A time later, after complete remittance of local
      inflammation, the pancreas was anastomosed to the jejunum. The postoperative
      outcome was uneventful, the patient being disease-free at more than 5 years after
      surgery. Thus, pancreatico-duodenectomy is a feasible and safe operation when
      performed in tertiary hepato-bilio-pancreatic centers, in selected cases.

PMID- 21853756
TI  - Exploration of perceptual and motor inhibition in children with traumatic brain
      injury.
AB  - Perceptual and motor inhibition were examined using conflict resolution tasks for
      12 children with traumatic brain injury and 24 matched controls. Direct
      comparisons of inhibition performances between the two groups showed a specific
      and disproportionate impairment of motor inhibition (compared with perceptual
      inhibition) for the children with traumatic brain injury, which suggests that
      inhibition processes might be differentially impaired in children after traumatic
      brain injury.

PMID- 21853757
TI  - The role of visual feedback in supervision of grammatical spelling.
AB  - Native French speakers (N = 24; M age = 20.1 yr.) were orally presented with
      sentences they were asked to write on a digitizing tablet, either with full
      visual feedback or with no visual feedback. The study assessed the extent to
      which the visual feedback contributed to supervising of verbal agreement
      processes, either postgraphically (detecting and revising any error that has been
      produced) or pregraphically (checking the graphemic plan before it is
      transcribed). The proportion of erroneous agreements was smaller with visual
      feedback (7%) than without (14%). The proportion of erroneous agreements that
      were spontaneously corrected was much higher with visual feedback (34%) than
      without (0%). There were significantly more pauses right before or within the
      transcription of the verbal inflection with visual feedback (8%) than without
      (3%).

PMID- 21853758
TI  - Illumination, background luminance, and perceptual learning in perception of
      achromatic colors.
AB  - Plateau's experiment, in which the bisection method was introduced, is recognized
      as the first psychophysical experiment ever done. That experiment was replicated
      and extended using modem imaging devices. First, participants with professional
      training in visual arts painted grayscales with no control on illumination. Then,
      the trained participants and the nontrained participants generated grayscales
      using a personal computer in three different conditions: a white background of a
      linearized monitor, a black background of that monitor, and a white background
      but without linearizing the monitor. Analyses showed that with artificial
      illumination, scales with steps more evenly spread were produced than with
      natural illumination. Humans do not seem to have a natural ability to use the
      bisection method properly. Experts seem to be able to judge the reflectance of
      distal stimuli, and perceptual learning played an important role in the
      perception of achromatic colors as found in prior literature.

PMID- 21853759
TI  - Relationship between hemispatial inattention and performance of activities of
      daily living in patients with schizophrenia.
AB  - This study investigated the relation of hemispatial inattention to the
      performance of daily functions in 32 patients with schizophrenia or
      schizoaffective disorder and in 31 healthy controls. They were tested on the
      relationship between a target cancellation task and the Activities of Daily
      Living Rating Scale-II (ADLRS-II). According to the results of the hemispatial
      inattention test, the patients with schizophrenia made more omissions in the
      cancellation test than the controls. In addition, the results showed a
      significant correlation between number of omissions on the cancellation test and
      the ADLRS-II score in the study participants. A statistically significant
      relationship was observed between hemispatial inattention and the functional
      status of patients with schizophrenia, and suggests the need to incorporate
      measures of visual attention into psychiatric rehabilitation assessments.

PMID- 21853760
TI  - Attitude and knowledge changes in collegiate dancers following a short-term, team
      centered prevention program on eating disorders.
AB  - Eating knowledge, nutritional knowledge, and psychological changes among female
      collegiate dancers were examined before and after a 4-wk. team-centered program
      on sport nutrition, exercise, and disordered eating consequences. Collegiate
      female dancers from two NCAA Division I institutions participated in a control (n
      = 19; M age = 19.1 yr., SD = 1.0) or intervention (n = 21; M age = 19.2 yr., SD =
      1.2) group. Measures were administered to both groups before and after
      intervention to assess eating disorders, depression, and nutritional and
      disordered eating knowledge. There was a statistically significant increase in
      scores on nutritional and overall eating disorder knowledge in the intervention
      group compared to the control group. Mean scores on depression, drive for
      thinness, body dissatisfaction, and maturity fears decreased in the intervention
      group.

PMID- 21853761
TI  - Use of a standard cane increases unipedal stance time during static testing.
AB  - The records of 11 consecutive qualifying patients were reviewed to evaluate
      whether use of a cane increased unipedal balance time during static testing.
      Measured with a stopwatch, the maximum unipedal balance time increased
      significantly with use of a single-point cane, whether standing on the left (M =
      14.4 sec.) or right (M = 16.7 sec.) lower limb. The results indicate that in
      clinical situations, sophisticated instruments are not needed to demonstrate the
      effects of a cane and that unipedal stance times obtained with a stopwatch can
      confirm the effectiveness of canes for increasing unipedal balance of patients
      and caregivers.

PMID- 21853762
TI  - Effects of compliance monitoring of vocal function exercises on voice outcome
      measures for normal voice.
AB  - This experimental study examined the efficacy of the vocal function exercise
      program in improving voice production in individuals with normal voices. 20 young
      women (M age = 22 yr.) with normal voices, 10 in the Monitored compliance group
      and 10 in the Unmonitored compliance group, received training in performing vocal
      function exercises followed by daily practice of the exercises for 28 consecutive
      days. Participants in the Monitored compliance group were required to submit
      audio or video recordings of their daily practice of vocal function exercises,
      and those in the Unmonitored compliance group were not required to record their
      daily practice sessions. Results indicated that while the participants in both
      groups significantly increased maximum phonation times and maximum phonational
      frequency ranges, those in the Monitored group improved significantly more than
      the participants in the Unmonitored group on these outcome measures.

PMID- 21853763
TI  - Multidimensional scaling of musical time estimations.
AB  - The aim of this study was to identify the psycho-musical factors that govern time
      evaluation in Western music from baroque, classic, romantic, and modern
      repertoires. The excerpts were previously found to represent variability in
      musical properties and to induce four main categories of emotions. 48
      participants (musicians and nonmusicians) freely listened to 16 musical excerpts
      (lasting 20 sec. each) and grouped those that seemed to have the same duration.
      Then, participants associated each group of excerpts to one of a set of sine wave
      tones varying in duration from 16 to 24 sec. Multidimensional scaling analysis
      generated a two-dimensional solution for these time judgments. Musical excerpts
      with high arousal produced an overestimation of time, and affective valence had
      little influence on time perception. The duration was also overestimated when
      tempo and loudness were higher, and to a lesser extent, timbre density. In
      contrast, musical tension had little influence.

PMID- 21853764
TI  - Influence of balance on oral-motor control of speech: a pilot investigation.
AB  - In this exploratory study, the interaction between motor coordination for balance
      and oral-motor control for speech was investigated in 31 typical college-aged
      women, ages 20 to 29 years (M = 22.3, SD = 2.1), recruited through the local
      university. Since speech is dependent on the control and coordination of the
      subsystems of the speech production mechanism, it was hypothesized that a
      difficult balance task would interfere with speech motor control. Oral-motor
      control was measured by diadochokinesis while participants were in a
      nonchallenging balance position (floor standing) and a challenging balance
      position (balance disk on one leg). Results indicated that individuals
      compensated for speech rate while having to maintain their balance for the
      syllable repetitions. However, the number of syllables repeated was significantly
      fewer while on the balance disk. In addition, a correlational analysis indicated
      that history of speech therapy services was related to poorer balance screening
      score. Directions for future research are discussed.

PMID- 21853765
TI  - Effect of an aerobic training program as complementary therapy in patients with
      moderate depression.
AB  - The aim of this study was to assess the effects of an aerobic training program as
      complementary therapy in patients suffering from moderate depression. 82 female
      patients weredivided into a group that received traditional pharmacotherapy
      (Fluoxetine 20 mg) and a group that received pharmacotherapy plus an aerobic
      training program. This program was carried out for eight consecutive weeks, three
      days per week, and included gymnastics, dancing, and walking. Depressive symptoms
      were measured with the Beck Depression Inventory and the ICD-10 Guide for
      Depression Diagnosis, both administered before and after treatments. The results
      confirm the effectiveness of the aerobic training program as a complementary
      therapy to diminish depressive symptoms in patients suffering from moderate
      depression.

PMID- 21853766
TI  - The role of attributional bias and visual stress on the improvement of reading
      speed using colored filters.
AB  - This study tested the predictions derived from two explanatory theoretical models
      of the effects of colored filters on reading speed: the theory of attributional
      bias and the theory of visual stress associated with reading. The experimental
      group consisted of 27 secondary school students (14 boys, 13 girls) diagnosed
      with the Meares-Irlen syndrome; the control group had 27 students paired in age
      and sex with the experimental group. The mean age of the sample was 12 years, 10
      months (SD = 8.9 mo.). The effects of colored filters on reading speed and
      accuracy were tested using a word reading test and a visual stress induction
      text. The presentation method tapped individuals' visual sensitivity and response
      criteria. The results support some predictions of the theory of attributional
      bias, but more research is needed to assess each theory of reading speed.

PMID- 21853767
TI  - Change in dexterity with sensory awareness training: a randomised controlled
      trial.
AB  - The role of sensory awareness in movement control is receiving increasing
      interest in sports and clinical literature as a feed-forward and feedback
      mechanism. The aim of the study was to assess the feasibility and effect of
      training in sensory awareness on dexterity in healthy adults. 29 healthy students
      were randomly allocated to a single-group, sensory awareness lesson with the
      dominant hand, the same lesson with the nondominant hand, or to a sham control
      group. Dexterity measures included the Purdue Pegboard Test, a grip-lift
      manipulandum, and perceived changes using a questionnaire. The sensory awareness
      lesson with the dominant hand produced a statistically significant improvement in
      mean dexterity compared to the control group, but not between the other two pairs
      of groups. The sensory awareness training paradigm is feasible and a single
      session improved dexterity in healthy adults.

PMID- 21853768
TI  - A pilot study of performance in young and middle-aged adults on verbal recall.
AB  - The objective was to explore whether middle-aged adults (M age = 48.9 yr.; n =
      26) differed on verbal recall from young adults (M age = 26.3 yr.; n = 26).
      Little data exist on the performance of middle-aged, healthy adults. Groups of
      young and middle-aged adults recalled words from the Rey Auditory Verbal Learning
      Test across six trials during a single session. The same 15 words were used for
      recall in Trials 1-5. Prior to the sixth trial, 15 distractor words were
      presented. Participants then recalled the original set of 15 words. No
      significant differences occurred on any of the recall trials. Although the power
      of this study was low, the effect of age is apparently quite small.

PMID- 21853769
TI  - Five-repetition sit-to-stand test: usefulness for older patients in a home-care
      setting.
AB  - The usefulness of the five-repetition sit-to-stand (FRSTS) test was assessed with
      older patients in a home-care setting. Records of 45 patients (> or = 65 years
      old) were examined for information on FRSTS test performance. 5 patients were
      excluded. 23 patients were unable to complete the test. For the 17 able to
      complete the FRSTS test, the time required was statistically significantly
      greater than age-stratified norms. For patients treated in a home-care setting,
      inability to complete the FRSTS test clearly underscores the test's limitations
      and the need for alternatives.

PMID- 21853770
TI  - Validation of a German version of the Sport Motivation Scale (SMS28) and
      motivation analysis in competitive mountain runners.
AB  - This study validated a German version of the Sport Motivation Scale (SMS28) and
      investigated the sex-specific and age-related differences in motivation of
      competitive mountain runners. Translation and cross-cultural adaptation of the
      SMS28 was based on translation and back-translation methodology. Acceptable
      validity of the German version of the SMS28 was indicated by the high
      correlations (.81 to .98) of scores on the seven subscales for the English and
      German versions completed by 15 subjects. Motivation analysis was performed with
      127 competitive male and female mountain runners. The seven subscales of the
      German version showed good internal consistency (Cronbach's coefficient alphas
      .70 to .85). Findings on motivation of competitive mountain runners were a
      decline across age groups of Intrinsic motivation toward accomplishment for both
      sexes and an age-related decline of External regulation only for females. These
      motivational changes might well be associated with the observed diminishing
      numbers of older participants in mountain running competitions.

PMID- 21853771
TI  - Validation of computer simulations for effects of eye gaze, sex, facial
      expression, and posture on perceived threat.
AB  - Two experiments were done to ascertain how well computer images of people
      communicated threat through the nonverbal cues of eye gaze, sex, facial
      expression, and posture. Results indicated the computer images produced valid and
      generalizable results. The strongest effects on threat were found for facial
      expression and posture. Smaller effects were found for sex and direction of eye
      gaze.

PMID- 21853772
TI  - Eye movements during mental rotation of nonmirrored and mirrored three
      dimensional abstract objects.
AB  - Eye movements were recorded while participants (N = 56) rotated mirrored and
      nonmirrored abstract, three-dimensional object pairs into different orientations
      to assess whether there were oculomotoric differences in fixation switches
      between mirrored and nonmirrored objects and how an object's plane and depth
      angle affected visual processing. Compared to other studies, especially depth
      rotation tasks were responsible for a difference in the sum of fixation switches.
      This difference seemed to be caused by an increase in incongruent fixation
      switches, while congruent ones remained stable. Theoretical and practical
      implications of findings are discussed.

PMID- 21853773
TI  - Authorship and sampling practice in selected biomechanics and sports science
      journals.
AB  - In some biomedical sciences, changes in patterns of collaboration and authorship
      have complicated the assignment of credit and responsibility for research. It is
      unclear if this problem of "promiscuous coauthorship" or "hyperauthorship"
      (defined as six or more authors) is also apparent in the applied research
      disciplines within sport and exercise science. This study documented the
      authorship and sampling of patterns of original research reports in three applied
      biomechanics (Clinical Biomechanics, Journal of Applied Biomechanics, and Sports
      Biomechanics) and five similar subdisciplinary journals within sport and exercise
      science (International Journal of Sports Physiology and Performance, Journal of
      Sport Rehabilitation, Journal of Teaching Physical Education, Measurement in
      Physical Education and Exercise Sciences, and Motor Control). Original research
      reports from the 2009 volumes of these biomechanics and sport and exercise
      journals were reviewed. Single authorship of papers was rare (2.6%) in these
      journals, with the mean number of authors ranging from 2.7 to 4.5. Sample sizes
      and the ratio of sample to authors varied widely, and these variables tended not
      to be associated with number of authors. Original research reports published in
      these journals in 2009 tended to be published by small teams of collaborators, so
      currently there may be few problems with promiscuous coauthorship in these
      subdisciplines of sport and exercise science.

PMID- 21853774
TI  - Speech intelligibility differences across sound classes with in-the-ear and free
      field microphones in quiet.
AB  - Speech intelligibility performance with an in-the-ear microphone embedded in a
      custom-molded deep-insertion earplug was compared with results obtained using a
      free-field microphone. Intelligibility differences between microphones were
      further analyzed to assess whether reduced intelligibility was specific to
      certain sound classes. 36 participants completed the Modified Rhyme Test using
      recordings made with each microphone. While speech intelligibility for both
      microphones was highly accurate, intelligibility with the free-field microphone
      was significantly better than with the in-the-ear microphone. There were
      significant effects of place and manner of sound production. Significant
      differences in recognition among specific phonemes were also revealed.
      Implications included modifying the in-the-ear microphone to transmit more high
      frequency energy. Use of the in-the-ear microphone was limited by significant
      loss of high-frequency energy of the speech signal which resulted in reduced
      intelligibility for some sounds; however, the in-the-ear microphone is a
      promising technology for effective communication in military environments.

PMID- 21853775
TI  - Asymmetry of force fluctuation during low and moderate intensity isometric knee
      extensions.
AB  - The purpose of this study was to investigate the asymmetry of force fluctuation
      during isometric knee extension at low and moderate intensities. 11 healthy men
      (M age = 21 yr., SD = 1) performed unilateral force matching tasks; sustained
      isometric knee extension at 20% and 30% maximal voluntary contraction (MVC).
      During the tasks, a mechanomyogram was measured by an accelerometer arrangement
      placed on the vastus lateralis. Although force fluctuation was not significantly
      different between the two legs at 20% MVC, it was higher in the left (weaker) leg
      than in the right (stronger) leg at 30% MVC. A significant difference in mean
      power frequency of the mechanomyographic signal between the two legs was also
      observed only at 30% MVC. These results suggest that the asymmetry of force
      fluctuation during isometric knee extension was not statistically significant at
      low intensity; however, it was significant at moderate intensity. These
      differences in force fluctuation between intensities might be influenced by
      different motor-unit firing rates in active muscle.

PMID- 21853777
TI  - Leadership and change commitment in the life insurance service context in Taiwan:
      the mediating-moderating role of job satisfaction.
AB  - The effects of transformational leadership and satisfaction were studied along
      with their interconnected effects (mediation and moderation) on commitment to
      change in the life insurance industry in two samples, sales managers and
      salespersons. A multiple mediated-moderated regression approach showed mediation
      and moderation to have statistically significant main effects on change
      commitment. Transformational leadership and satisfaction made a more important
      contribution to change commitment while job satisfaction had a mediating and
      moderating role that could enhance the relationships between leadership and
      change commitment. This information is of importance in building successful
      change commitment associations with customers.

PMID- 21853776
TI  - Differences in decision-making development between expert and novice invasion
      game players.
AB  - This cross-sectional study investigated the differences between young expert
      soccer players' (n = 55) and novice players' (n = 74) decision-making ability
      during performance of invasion games (ages: 7-8, 9-10, 11-12, and 13-14 years).
      Decision-making ability was assessed in invasion games that were appropriately
      modified for age and expertise. Games were modified to meet the developmental
      needs and previous learning of the participants, so interference between motor
      execution and decision making was minimized. Game performance was videotaped, and
      measures of cognitive components were developed from observational analysis.
      Decision making was measured at two levels: (a) decision making restricted to the
      selection of the technical-tactical skills (passing, moving with the ball,
      getting free, marking, tackling, double teaming, and interception) and (b)
      decision making in the adaptation to the tactical context of the game. Expert
      players remained superior in decision-making ability when variation in skill
      execution was controlled. Decision-making differences between levels of expertise
      decreased with age with regard to the first level (skill selection) and increased
      with age in relation to the second level (tactical-context adaptation). Findings
      are discussed in terms of implications for instructional focus and task design.

PMID- 21853778
TI  - Visuospatial attention lateralization in volleyball players and in rowers.
AB  - In the present study, differences in visuospatial attention lateralization were
      evaluated in athletes engaged in open-compared to closed-skill sports and
      sedentary nonathletes. 23 volleyball players (open skill; Italian national level
      and regional level), 10 rowers (closed skill, Italian national level), and 23
      sedentary participants responded to a computerized line-length judgment task.
      Five lines, differing in the length of their right and left segments, were
      randomly presented; the respondent made a forced-choice decision about the
      respective length of the two segments. Volleyball players responded significantly
      faster; those at the higher competitive level were also more accurate, making a
      statistically significantly lower number of leftward errors as compared with
      rowers and controls. If such responses are due to training rather than self
      selection of ability, then the results may suggest the possibility of changing
      the distribution of visuospatial attention by training in open-skill sports.

PMID- 21853779
TI  - Prediction of experimental pain sensitivity by attention to pain-related stimuli
      in healthy individuals.
AB  - The aim of the present study was to assess the predictive power of the processing
      of pain-related information, comprising concepts of hypervigilance to pain, pain
      catastrophizing, and pain-related anxiety (questionnaires) as well as attentional
      processes related to pain-related stimuli (dot-probe task) in explaining
      individual differences in experimental pain sensitivity (pressure/thermal pain
      threshold). In 160 healthy participants (ages 13-61; 80 females), results of
      hierarchical multiple regression analyses showed that self-reported
      hypervigilance contributed significantly to the prediction of pain sensitivity,
      whereas pain catastrophizing and anxiety did not. However, inconsistent with
      prediction, the effect was in the opposite direction, indicating that vigilance
      to pain sensations or stimuli is associated with lower pain sensitivity in
      healthy individuals. Entering the attentional bias indices from the dot-probe
      task showed that an increased bias to pain words is related to higher
      experimental pain sensitivity, which confirms the hypothesis.

PMID- 21853780
TI  - Reading words with jumbled characters in Japanese.
AB  - Rayner, et al. (2006) was replicated with 36 Japanese undergraduates who read
      Japanese sentences in which characters were transposed in one word at the
      beginning, middle, or end. The same pattern of reading delays in relation to
      transposition location was found but in smaller magnitude. Transposition of
      characters at the beginning of words caused the largest delay in reading.

PMID- 21853781
TI  - Knowledge of eating disorders among collegiate administrators, coaches, and
      auxiliary dancers.
AB  - Knowledge of eating disorders, confidence in knowledge, and attendance of eating
      disorder educational programs were assessed among NCAA Division I and II
      university administrators (n = 61), coaches (n = 44), and dancers (n = 53). A
      questionnaire assessed knowledge in 5 domains: etiology, signs and symptoms,
      management and treatment, risk factors, and prevention and education. Overall,
      dancers' knowledge and previous attendance were significantly lower than
      administrators' and coaches'. There was inconsistency between participants'
      confidence in answers and the correctness of their answers. Education is
      necessary for improving knowledge and reducing risky behaviors in auxiliary
      dancers.

PMID- 21853782
TI  - Effect of display size on visual attention.
AB  - Attention plays an important role in the design of human-machine interfaces.
      However, current knowledge about attention is largely based on data obtained when
      using devices of moderate display size. With advancement in display technology
      comes the need for understanding attention behavior over a wider range of viewing
      sizes. The effect of display size on test participants' visual search performance
      was studied. The participants (N = 12) performed two types of visual search
      tasks, that is, parallel and serial search, under three display-size conditions
      (16 degrees, 32 degrees, and 60 degrees). Serial, but not parallel, search was
      affected by display size. In the serial task, mean reaction time for detecting a
      target increased with the display size.

PMID- 21853783
TI  - Past speech therapy experiences of individuals exploring a new stuttering
      treatment.
AB  - Perceptions of benefits of speech therapy, success of therapy across clinical
      settings, reasons for returning to therapy, client-clinician relationships, and
      clinicians' competency were assessed in 57 participants (47 men, 10 women; M age
      = 34 yr.) trying a new therapy. A majority of respondents had cumulatively five
      or more years in therapy and at least two stuttering therapies. Respondents rated
      university or hospital settings as more successful than services in public
      schools. 70% of the respondents noted difficulty communicating basic needs; they
      blamed themselves for inability to maintain posttherapeutic gains while
      perceiving their clinicians to be competent and attentive--although 47% of the
      respondents had minimal to no contact with their therapist after therapy.

PMID- 21853784
TI  - Effects of high-frequency yoga breathing called kapalabhati compared with breath
      awareness on the degree of optical illusion perceived.
AB  - Prior research has shown that methods of meditation, breath control, and
      different kinds of yoga breathing affect attention and visual perception,
      including decreasing the size of certain optical illusions. Evaluating
      relationships sheds light on the perceptual and cognitive changes induced by yoga
      and related methods, and the locus of the effects. In the present study, the
      degree of optical illusion was assessed using Muller-Lyer stimuli before and
      immediately after two different kinds of practice, a high frequency yoga
      breathing called kapalabhati, and breath awareness. A nonyoga, control session
      tested for practice effects. Thirty participants (with group M age = 26.9 yr., SD
      = 5.7) practiced the two techniques for 18 min. on two separate days. The control
      group had 15 nonyoga practitioners assessed before and after 18 min. in which
      they did not perform any specific activity but were seated and relaxed. After
      both kapalabhati and breath awareness there was a significant decrease in the
      degree of optical illusion. The possibility that this was due to a practice or
      repetition effect was ruled out when 15 nonyoga practitioners showed no change in
      the degree of illusion when retested after 18 min. The changes were interpreted
      as due to changes in perception related to the way the stimuli were judged.

PMID- 21853785
TI  - Rapid serial visual presentation display on a small screen: reading Chinese while
      walking.
AB  - This study examined the effects of presentation unit (word-by-word or single
      line) and presentation duration [171, 213, 240, and 308 msec. per character
      (msec./C)] on the comprehension of Chinese rapid serial visual presentation
      (RSVP) displays read from the small screen of a mobile phone in three different
      contexts (seated, walking on a treadmill, and walking through an outdoor course).
      30 native Chinese readers ages 19 to 26 were recruited as participants. Scores on
      reading comprehension showed that presentation unit and presentation duration
      significantly affected reading comprehension, and interactions between factors
      were also significant. When the presentation unit was word-by-word, no
      significant difference in reading comprehension was observed under different
      presentation durations. However, when the presentation unit was a single line,
      reading comprehension deteriorated with the shortest presentation duration of 171
      msec./C. With regard to context, participants had a higher mean reading
      comprehension score in the seated context than in walking contexts, but the
      difference was not significant.

PMID- 21853786
TI  - Tailoring education to meet nurses' needs.

PMID- 21853787
TI  - Feeling proud to be a nurse.

PMID- 21853789
TI  - Lack of nursing focus in some workforce reviews.

PMID- 21853788
TI  - Signifying Mary.

PMID- 21853790
TI  - Earthquake 2011.

PMID- 21853791
TI  - Reflecting on nursing and the art of caring.

PMID- 21853792
TI  - Budget will increase disparities.

PMID- 21853793
TI  - Examining the barriers to RN transition for students on competency assessment
      programmes.

PMID- 21853794
TI  - New Zealand-educated workforce could be compromised.

PMID- 21853795
TI  - Changing perceptions.

PMID- 21853796
TI  - Transitioning to practice.

PMID- 21853797
TI  - Pain--the fifth vital sign.

PMID- 21853798
TI  - ICN's membership dilemma.

PMID- 21853799
TI  - Finding a vision for the future of post-registration nursing education.

PMID- 21853800
TI  - Protecting women's rights.

PMID- 21853801
TI  - MMP delivers for women.

PMID- 21853802
TI  - [Observation, the first care intervention for a baby].

PMID- 21853803
TI  - [Reengineering of the State puericulture degree].

PMID- 21853804
TI  - [Caring, assisting the baby and the parents].

PMID- 21853805
TI  - [The art of parenting in the world].

PMID- 21853806
TI  - [Prematurity and learning disorders].

PMID- 21853807
TI  - [The 9-18 month period, adequate for discovering the world].

PMID- 21853808
TI  - [Taking care of the vision in children. To look in order to learn to watch].

PMID- 21853809
TI  - [The development of visual functions in children].
AB  - Visual function is based on the eye, but it is thanks to the cognitive processing
      of sensory information that the individual adapts his behaviour and gaze. Visual
      maturation is acquired gradually over the first 3 years. That is why it is
      important to detect any visual disorder before the age of 3.

PMID- 21853810
TI  - [Amblyopia, a public health problem].
AB  - Amblyopia or the alteration of the visual function is a common and disabling
      condition which takes various forms. Screening is carried out during a baby's
      first week of life and then at regular intervals during early childhood. It is a
      public health issue insofar as the disorders are curable and treatment is
      effective when they are detected early.

PMID- 21853811
TI  - [Screening tests for visual disorders].
AB  - Testing eyesight from a very early age is both medically as well as politically
      motivated. The attention paid to children's eyesight by ophthalmologists,
      paediatricians and doctors in early childhood or school health centres should be
      supported by a systematic eyesight assessment and the refunding of the necessary
      collyrium.

PMID- 21853812
TI  - [Screening for visual disorders in pre-primary school].
AB  - Children's vision develops very early on in life and constitutes their first
      connection with their surroundings. Recommendations emphasise the importance of
      early screening to improve learning at school. The pre-primary school period,
      between the ages of 3 and 6 is the ideal time for this. Child care nurses thereby
      have an important role to play in terms of health education and orientation.

PMID- 21853813
TI  - [Young children's optical equipment].
AB  - Young children's eyewear benefits from technical and technological progress and
      the attention paid by professionals to children's vision. Beyond the aesthetics
      of the frames, the quality of the lenses and the accuracy of the correction
      enable a child's eyesight to be maintained or improved, with the cooperation of
      the parents.

PMID- 21853814
TI  - [The eye and the perception of reality through visual arts].
AB  - Artists' view on the world and the way they convey it in their work provide
      avenues towards understanding the evolution of our societies, as well as the
      status of scientific knowledge. Reflection of an ophthalmologist and painter who
      has explored view and gaze through the production of visual arts.

PMID- 21853815
TI  - [Bibliography elements].

PMID- 21853816
TI  - [A new approach to cancer in 15-25 year olds].
AB  - The specificity of adolescence and early adulthood with people suffering from
      cancer requires adapted and specific care by nursing teams. The paediatric
      oncology and medical oncology teams at the Institut Curie in Paris, faced with
      such issues, have been working more closely together to create a special unit for
      15-25 year olds.

PMID- 21853817
TI  - [The integration of disabled children in childcare facilities].
AB  - The issue of the integration of young disabled children from early childhood
      questions our society both in terms of the place of disability as well as with
      regard to parenting. It is urgent to reflect on the training of childcare
      professionals and on the need to link theories and practice, to ensure everyone
      participates in this integration.

PMID- 21853818
TI  - [The psychological aspects of enuresis in children and teenagers].
AB  - A retrospective study over seven years shows a high frequency of underlying
      psychological dimensions to enuresis, mainly regressive and passive, but also
      aggressive and erotic. It is therefore important to understand the meaning of
      this symptom and to take into account, in the treatment, underlying affective
      disorders.

PMID- 21853819
TI  - [4/12 Cranial injury].

PMID- 21853820
TI  - Redesigning services around patients and their doctors: the continuing relevance
      of lean thinking transformation.

PMID- 21853821
TI  - Diagnostic error: the Achilles' heel of patient safety?

PMID- 21853822
TI  - Including pharmacists on consultant-led ward rounds: a prospective non-randomised
      controlled trial.
AB  - This study aimed to compare interventions made by pharmacists attending
      consultant-led ward rounds in addition to providing a ward pharmacy service, with
      those made by pharmacists providing a word pharmacy service alone. A prospective
      non-randomised controlled study on five inpatient medical wards was carried out
      at two teaching hospitals. A mean of 1.73 physician-accepted interventions were
      made per patient for the study group, compared to 0.89 for the control (Mann
      Whitney U, p < 0.001) with no difference between groups in the nature or clinical
      importance of the interventions. One physician-accepted intervention was made
      every eight minutes during the consultant-led ward rounds, compared to one every
      63 minutes during a ward pharmacist visit. Pharmacists attending consultant-led
      ward rounds in addition to undertaking a ward pharmacist visit make significantly
      more interventions per patient than those made by pharmacists undertaking a ward
      pharmacist visit alone, rectifying prescribing errors and optimising treatment.

PMID- 21853823
TI  - Misdiagnosis: analysis based on case record review with proposals aimed to
      improve diagnostic processes.
AB  - Diagnostic error underlies about 10% of adverse events occurring in hospital
      practice. However, there have been very few studies considering means of
      improving the mechanisms of diagnosis. As a result, misdiagnosis has been
      described as 'the next frontier for patient safety'. In this study of case
      records of patients admitted to hospital as emergencies, some key factors that
      may underlie diagnostic errors were assessed. From these observations,
      possibilities for improving the quality of diagnosis and the planning of
      subsequent care are explored. This paper shows that cognitive biases, believed to
      distort diagnostic conclusions, can be applied quite specifically to stages in
      clinical care. These observations led to the proposal of a clinical assessment
      with a method designed to encourage analytical reasoning. In addition, minor
      defects in standard practice are shown to adversely influence diagnosis. The
      findings of this study offer possible means of improving the quality of diagnosis
      and subsequent patient care, and perhaps pave the way for prospective studies.

PMID- 21853824
TI  - 'August is always a nightmare': results of the Royal College of Physicians of
      Edinburgh and Society of Acute Medicine August transition survey.
AB  - An electronic survey was used to assess perceptions of the disruption caused by
      the August transition and explore support for possible solutions. In total, 763
      responses from members and fellows of the Royal College of Physicians of
      Edinburgh and the Society of Acute Medicine were received. The majority perceived
      the August transition to have a negative impact on patient care (93.1%), patient
      safety (90.4%) and training (57.8%) for a period of up to one month. In total
      680/737 respondents wished to shift away from a single changeover day, with
      strong support for a staggered changeover by grade. Changes to consultant working
      practices were felt to be beneficial, especially the cancellation of outpatient
      clinics (75%) and the restriction of leave (69.9%). Further use of shadowing
      (74.1%) and online induction (37%) was supported. This paper concludes that there
      is a high degree of support for structured change to the current provisions for
      junior doctor changeover.

PMID- 21853825
TI  - Learning professionalism: a personal view.

PMID- 21853826
TI  - The role of the 'specialist' in healthcare.

PMID- 21853827
TI  - General practice in the new world.

PMID- 21853828
TI  - Weekend admission and mortality from acute exacerbations of chronic obstructive
      pulmonary disease in winter.
AB  - Historically, acute medical staffing numbers have been lower on weekends and in
      winter numbers of medical admissions rise. An analysis of acute exacerbations of
      chronic obstructive pulmonary disease (AECOPD) admissions to Portsmouth Hospitals
      over a seven-year period was undertaken to examine the effects of admission on a
      weekend, of winter, and with the opening of a medical admissions unit (MAU). In
      total, 9,915 admissions with AECOPD were identified. Weekend admissions accounted
      for 2,071 (20.9%) of cases, winter accounted for 3,026 (30.5%) admissions, and
      522 (34.4%) deaths. Adjusted odds ratio (OR) for death on day 1 after winter
      weekend admission was 2.89 (95% confidence interval (CI) 1.035 to 8.076). After
      opening the MAU, the OR for death day 1 after weekend winter admission fell from
      3.63 (95% CI 1.15 to 11.5) to 1.65 (95% CI 0.14 to 19.01). AECOPD patients have
      an increased risk of death after admission over a weekend in winter and this
      effect was reduced by opening a MAU. These findings have implications for the
      planning of acute care provision in different seasons.

PMID- 21853829
TI  - The placebo enigma revisited.

PMID- 21853830
TI  - 'The tubercular diabetic': the impact of diabetes mellitus on tuberculosis and
      its threat to global tuberculosis control.
AB  - The incidence and prevalence of diabetes mellitus (DM) is rapidly increasing
      across the globe. Tuberculosis (TB), meanwhile, remains a significant problem in
      low and middle income countries fuelled by high rates of HIV/AIDS. This article
      explores the long recognised but underappreciated connection between the two,
      revealing that DM makes a substantial contribution to the burden of incident TB
      around the world and may also worsen TB severity and treatment outcome. The dual
      management of the diseases may be challenging but must be addressed, both in low
      and high income settings, because the rising worldwide diabetes burden poses a
      threat to global TB control.

PMID- 21853831
TI  - Resuscitation of the written word: meeting the standard for cardiac arrest
      documentation.
AB  - The aim of this study was to audit cardiac arrest documentation within a UK
      teaching hospital, survey the regional use of proformas for data collection, and
      consider the need for a standardised national template. A prospective audit
      comparing cardiac arrest documentation to General Medical Council (GMC)
      professional standards and the 'Utstein' fields was carried out, along with a
      survey of regional resuscitation officers for the use of standardised templates.
      The main outcome measures were the design of 'best practice' template using GMC
      guidelines and the 'Utstein' fields. An audit of medical notes involving a
      cardiac arrest call against the template was performed. There was limited
      documentation concerning process, events and outcome of arrest calls, as well as
      minimal regional use of standard templates or consensus on the essential content
      of medical documentation. Documentation of cardiac arrests in the Leeds Teaching
      Hospitals does not meet the 'Utstein' recommendations to provide enough
      information for audit of cardiac arrest procedure. The regional survey indicates
      that this problem is likely to be widespread.

PMID- 21853832
TI  - Tuberculosis in the 21st century.

PMID- 21853833
TI  - HIV--early diagnosis: key to improved prognosis and the reduction of onward
      transmission.

PMID- 21853834
TI  - Modern approaches to multiple sclerosis.

PMID- 21853835
TI  - End-of-life decisions in acute hospitals.

PMID- 21853836
TI  - A case of hiccoughs.

PMID- 21853837
TI  - Acute renal failure in diabetes: looking beyond diabetic retinopathy.

PMID- 21853838
TI  - Emergency oxygen use in adult patients: concise guidance.
AB  - There is considerable controversy concerning the benefits and risks of oxygen
      treatment in many situations and healthcare professionals receive conflicting
      advice about safe oxygen use. The British Thoracic Society (BTS) has published up
      to-date, evidence-based guidelines for emergency oxygen use in the UK in order to
      encourage the safe use of oxygen in emergency situations and improve consistency
      of clinical practice. The purpose of this concise guideline is to summarise the
      key recommendations, particularly concerning emergency oxygen use in the hospital
      setting.

PMID- 21853839
TI  - Does this patient have atopic asthma?

PMID- 21853840
TI  - Does this patient have an immunodeficiency?

PMID- 21853841
TI  - Does this patient have vasculitis?

PMID- 21853842
TI  - Does this patient with urticaria/angioedema have anaphylaxis?

PMID- 21853843
TI  - Does this patient have periodic fever syndrome?

PMID- 21853844
TI  - A small left pupil and a headache.

PMID- 21853845
TI  - Cushing's syndrome with low levels of serum cortisol: the role of inhaled
      steroids.

PMID- 21853846
TI  - Yew tree poisoning: a near-fatal lesson from history.

PMID- 21853847
TI  - Angina without 'strangling and anxiety of the breast'.

PMID- 21853848
TI  - Emergency medical readmission: long-term trends and impact on mortality.

PMID- 21853849
TI  - Improving outcomes following percutaneous endoscopic gastrostomy (PEG)--a seven
      day waiting policy is essential.

PMID- 21853850
TI  - Are upper gastrointestinal cancer two week referrals an appropriate use of
      National Health Service resources?

PMID- 21853851
TI  - Clothing maketh the man.

PMID- 21853852
TI  - Can the multidisciplinary input of an asthma nurse specialist and respiratory
      physician improve the discharge management of acute asthma admissions?

PMID- 21853853
TI  - Display lag and gain effects on vection experienced by active observers.
AB  - BACKGROUND: This study examined the effects of display lag and gain on visual
      self-motion perception (i.e., vection) in active observers. METHODS: Our subjects
      viewed displays simulating self-motion in depth while physically oscillating
      their heads from side to side at approximately 1 Hz. Their horizontal head
      movements were recorded and incorporated into self-motion displays with four
      levels of added lag (0, 50, 100,and 200 ms; baseline system lag was 113 ms) and
      three levels of gain (i.e., subjects' head movements were either not incorporated
      into the display or were incorporated at either the same or twice the amplitude).
      At the end of each trial, subjects rated the strength of their perceived self
      motion in depth. RESULTS: While increasing display lag above baseline by an
      additional 50 ms impaired vection strength ratings, increasing display lag beyond
      this level eventually improved vection. For example, 200 ms added display lag
      produced vection strength ratings that were similar to those found with the
      baseline lag. As expected, larger simulated display gains were shown to improve
      vection strength ratings regardless of the level of added display lag.
      CONCLUSIONS: We conclude that increasing display lag during active head
      oscillation only impairs vection until the resulting sensory conflict becomes too
      great to tolerate. Beyond this critical level of lag, the visual system appears
      to override or downplay such sensory conflicts.

PMID- 21853854
TI  - Tolerance to extended galvanic vestibular stimulation: optimal exposure for
      astronaut training.
AB  - BACKGROUND: We have developed an analogue of postflight sensorimotor dysfunction
      in astronauts using pseudorandom galvanic vestibular stimulation (GVS). To date
      there has been no study of the effects of extended GVS on human subjects and our
      aim was to determine optimal exposure for astronaut training based on tolerance
      to intermittent and continuous galvanic stimulation. METHODS: There were 60
      subjects who were exposed to a total of 10.5 min of intermittent GVS at a peak
      current of 3.5 mA or 5 mA. A subset of 24 subjects who tolerated the intermittent
      stimulus were subsequently exposed to 20-min continuous stimulation at 3.5 mA or
      5 mA. RESULTS: During intermittent GVS the large majority of subjects (78.3%)
      reported no or at most mild motion sickness symptoms, 13.3% reported moderate
      symptoms, and 8.3% experienced severe nausea and requested termination of the
      stimulus. During 20-min continuous exposure, 83.3% of subjects reported no or at
      most mild motion sickness symptoms and 16.7% (all in the 5-mA group) experienced
      severe nausea. CONCLUSION: Based on these results, we propose two basic modes of
      GVS application to minimize the incidence of motion sickness: intermittent high
      (5 mA) amplitude, suited to simulation of intensive operator tasks requiring a
      high-fidelity analogue of postflight sensorimotor dysfunction such as landing or
      docking maneuvers; and continuous low (3.5 mA) amplitude stimulation, for longer
      simulation scenarios such as extra vehicular activity. Our results suggest that
      neither mode of stimulation would induce motion sickness in the large majority of
      subjects for up to 20 min exposure.

PMID- 21853855
TI  - In-flight hypoxia events in tactical jet aviation: characteristics compared to
      normobaric training.
AB  - INTRODUCTION: Hypoxia continues to be a significant threat in military aviation.
      In an attempt to counter the hypoxia threat, military jet aviators receive
      periodic training using a reduced oxygen breathing device (ROBD). This study
      explored the characteristics of in-flight hypoxia events among tactical jet
      aviators and compared reported symptoms to those experienced during ROBD
      training. METHODS: An anonymous survey was administered to naval aviators prior
      to aviation physiology training. The survey queried them about previous in-flight
      hypoxia encounters and the symptoms they experienced. These data were then
      compared to symptom data from a previous ROBD training survey using Chi-square
      analyses. RESULTS: Of the 566 aviators who completed the survey, 112 (20%)
      reported experiencing hypoxia symptoms in a tactical jet aircraft and 64 aviators
      (57%) indicated they were not wearing the required oxygen mask when the incident
      first occurred. The results also revealed only 21% of hypoxia events were
      reported in aviation hazard reports and the three most commonly recorded in
      flight hypoxia symptoms were tingling (54%), difficulty concentrating (32%), and
      dizziness (30%). Chi-square analyses revealed statistically significant
      differences in frequency of reporting between 5 of 16 symptoms encountered in
      flight compared to ROBD training. DISCUSSION: The present investigation is the
      first survey-based study of hypoxia events in U.S. naval aviation. The study
      reveals in-flight, mask-on hypoxia has a similar overall reported symptom profile
      to ROBD training. Further, results suggest increased oxygen-mask compliance among
      these aviators may be necessary to effectively combat in-flight hypoxia.

PMID- 21853856
TI  - Airport quarantine inspection, follow-up observation, and the prevention of
      pandemic influenza.
AB  - INTRODUCTION: After a report of H1N1 novel influenza in Mexico and North America,
      Japan conducted onboard quarantine inspections from late April 2009. The
      detection rate in border quarantine inspection is low due to incubation period
      and thus inspection is considered to be ineffective in blocking the entry of
      influenza. However, little is known about the concomitant effects of such
      inspection, such as increased traceability, upon secondary transmission. METHODS:
      Epidemiological data were collected from the web sites of the Department of
      Health, Labor, and Welfare of Japan and the National Institute of Infectious
      Diseases of Japan. The number of weekly patients with H1N1 pandemic influenza in
      eight districts of Japan was summarized. The number of patients who passed
      through quarantine inspection at the airports was also calculated. A person with
      overseas travel history was defined as a person who had a flight only from the
      United States, Canada, or Mexico and passed through the quarantine inspection
      (according to the quarantine policy of the Japanese government). The numbers were
      adjusted for the population of each district and expressed as the number of
      patients per one million people. RESULTS: Despite Kanto district having the
      largest population, the number of patients with H1N1 novel influenza was
      relatively small. The total number of cases in each district correlated inversely
      to the percentage of cases with airport quarantine inspection. DISCUSSION:
      Quarantine inspection at the airports, follow-up observation by local
      authorities, and overall concomitant efforts may have contributed to secondary
      infection control in Japan.

PMID- 21853857
TI  - Whole body vibration in helicopters: risk assessment in relation to low back
      pain.
AB  - INTRODUCTION: Helicopter pilots are exposed to whole body vibration (WBV) in
      their working environment. WBV has been associated with low back pain (LBP) and
      helicopter pilots have a high prevalence for LBP compared with other professions.
      The aim of this study was to develop a test protocol for measuring helicopters
      with ISO 2631-1 and to perform a whole body vibration risk assessment based on
      the European Vibration Directive in a number of commonly used military and
      civilian helicopters. Both absolute values and individual difference in current
      helicopter types are of interest in order to evaluate the possible role of
      vibration in LBP in helicopter pilots. METHODS: In operationally relevant
      maneuvers, six helicopters were tested. In order to standardize measurements,
      each continuous flight was split into 15 separate maneuvers. A model of a working
      day exposure pattern was used to calculate A(8) vibration magnitudes for each
      helicopter. RESULTS: The vibration A(8) exposure estimates ranged from 0.32-0.51
      m x s(-2) during an 8-h working day A(8). This compares with EU and ISO lower
      bounds risk criteria of 0.5 and 0.43 m x s(-2) A(8), respectively. DISCUSSION:
      Despite the vibration levels being relatively low, helicopter pilots report a
      high incidence of LBP. It is possible that helicopter pilot postures increase the
      risk of LBP when combined with WBV. The test protocol used in this study could be
      generally applied for other rotary winged aircraft testing to allow for
      comparison of WBV results. Data from different flight phases could be used to
      model different exposure profiles.

PMID- 21853858
TI  - Military parachuting injuries, associated events, and injury risk factors.
AB  - INTRODUCTION: The purpose of this investigation was to examine injury incidence,
      events associated with injury, and injury risk factors during parachuting in an
      Army airborne infantry unit. METHODS: Injury data were obtained by the
      investigators on the drop zone and confirmed by a physician. Operational data
      (potential injury risk factors) were obtained from routine reports published by
      the infantry unit. Weather data were obtained using a Kestrel Model 4500 pocket
      weather tracker. RESULTS: There were a total of 23,031 jumps resulting in 242
      injured soldiers for a crude injury incidence of 10.5 per 1000 jumps. Parachute
      entanglement incidence was 0.5 per 1000 jumps. Where an event associated with the
      injury could be determined (67% of cases), these included ground impact (75%),
      static line problems (11%), tree landings (4%), entanglements (4%), and aircraft
      exits (3%). Univariate analysis showed that higher injury risk was associated
      with night jumps (versus day jumps), combat loads (versus unloaded jumps), higher
      wind speeds, higher dry bulb temperatures, higher humidity, C17 Globemaster or
      C130 Hercules aircrafts (compared to the other aircraft), exits through aircraft
      side doors (versus tailgates), and entanglements. Multivariate analysis indicated
      that independent risk factors for injuries included night jumps, combat loads,
      higher wind speeds, higher dry bulb temperatures, and entanglements. DISCUSSION:
      This investigation provided injury incidence, events associated with injury, and
      quantitative assessments of injury risk factors and their interactions during
      military parachuting. An appreciation of these subjects can assist medical and
      operational planners in further reducing the incidence of injury during airborne
      operations.

PMID- 21853859
TI  - Nutrition and resistance exercise during reconditioning from unloading.
AB  - INTRODUCTION: The recovery of muscle size and function following musculoskeletal
      unloading has received little attention in the scientific literature. Nutritional
      factors such as total energy, protein intake, and the pre- and/or post-exercise
      consumption of amino acid-carbohydrate (AACHO) have been shown to be important
      for enhancing training adaptations in recreational exercisers. PURPOSE: A
      preliminary study was conducted to explore the interaction between nutrition and
      resistance exercise during reconditioning from unloading. METHODS: Muscle CSA,
      strength, and endurance were measured during a control period following 30 d of
      unilateral lower limb suspension (Post-ULLS) and after 18 d of reconditioning
      (ReCon). Six participants consumed either AACHO (979 kJ, 36 g carbohydrate, 22.5
      g protein) or placebo (PLAC) prior to resistance exercise (3 d x wk(-1)) during
      reconditioning. Total daily energy and macronutrient intake were evaluated from
      dietary journals. RESULTS: From Post-ULLS to ReCon, muscle endurance increased
      1.1 +/- 0.6 min in AACHO and decreased 1.3 +/- 0.7 min in PLAC. Muscle CSA (6 +/-
      2 vs. 5 +/- 3 cm2) and strength (105 +/- 53 vs. 81 +/- 37 N) increased similarly
      in AACHO and PLAC, respectively. When groups were pooled there was a significant
      correlation between daily protein intake and the recovery of muscle CSA (r =
      0.81). DISCUSSION: Although our findings are preliminary, timing AACHO intake
      during reconditioning was beneficial for muscular endurance, while overall
      protein intake was associated with increased muscle size. A systematic evaluation
      into the synergistic relationship between nutrition and exercise during muscular
      recovery from prolonged unloading is warranted.

PMID- 21853860
TI  - Cardiopulmonary resuscitation during spaceflight: examining the role of timing
      devices.
AB  - INTRODUCTION: The majority of International Space Station (ISS) astronauts
      represent nonmedical professions. In order to serve as Crew Medical Officers
      (CMO), future crewmembers receive 40-70 h of medical training within 18 mo before
      missions, including cardiopulmonary resuscitation (CPR) per the Guidelines of the
      American Heart Association. CPR compliance with the Guidelines is known to vary
      even among trained clinicians, let alone minimally trained caregivers (e.g.,
      bystanders, nonphysician astronauts). The purpose of this study was to evaluate
      the effect of timing devices, including audible metronomic tones, on CPR
      performed by nonmedical personnel, specifically 40 astronaut analogues trained in
      a fashion and within a timeframe similar to an ISS astronaut. METHODS: Twenty
      bystander pairs performed two-person CPR for 4 min on a simulated cardiac arrest
      patient using three interventions: 1) CPR with no timing devices; 2) CPR with
      metronomic tones for chest compressions; and 3) CPR with a timing device and
      metronome for coordinating ventilation and compression rates, respectively. Each
      CPR performance was evaluated for compliance with the (then current) 2000 AHA
      Guidelines. RESULTS: Numbers of breaths and compressions significantly deviated
      from target values in the first two interventions (38 and 42 breaths vs. target
      of 32 breaths; 282 and 318 compressions vs. target of 240 compressions); the use
      of timing devices for both components of CPR resulted in significant improvement
      (32 breaths and 231 compressions). CONCLUSIONS: CPR timing devices that
      coordinate both breaths and compressions improve compliance of astronaut analogue
      rescuers with CPR guidelines, and may improve overall CPR performance and
      outcome.

PMID- 21853861
TI  - To dive or not to dive with bleomycin: a practical algorithm.
AB  - BACKGROUND: Bleomycin is used in the treatment of different cancers, but possible
      side effects of interstitial pneumonitis and fibrosis are associated with
      increased concentrations of oxygen. Therefore, clinicians are reluctant to
      declare young people fit for scuba diving after bleomycin treatment, because
      scuba divers might be exposed to high partial pressures of oxygen. METHODS: Based
      on a survey, 16 patients treated with bleomycin for either testicular/germ cell
      cancer or Hodgkin's disease were evaluated according to an algorithm to assess
      their fitness to dive. The algorithm is based on a review of the literature
      related to oncology, anesthesiology, and diving medicine. RESULTS: According to
      our protocol, 12 of the 16 patients were fit for scuba diving. However, the two
      groups of cancer patients showed considerable difference with regard to fitness
      for diving, i.e., 10 of 11 patients with testicular/germ cell cancer compared
      with 2 of 5 patients with Hodgkin's disease. CONCLUSIONS: The algorithm can be
      used by physicians and diving organizations to assess fitness for scuba diving
      after bleomycin treatment. However, patients with Hodgkin's disease treated with
      a combination of bleomycin and radiation may be at higher risk of radiation
      induced pulmonary problems and are therefore more likely to be unfit for scuba
      diving.

PMID- 21853862
TI  - The geometry of high angle of attack maneuvers and the implications for Gy
      induced neck injuries.
AB  - INTRODUCTION: Modern super agile fighter aircraft have significantly expanded
      maneuverability envelopes, often involving very high angles of attack (AOA) in
      the post-stall region. One such maneuver is the high AOA velocity vector roll.
      The geometry of this flight maneuver is such that during the roll there is a
      significant lateral C load imposed on the unrestrained head-neck complex of the
      pilot. METHODS: A mathematical analysis of the geometric relationship determining
      the magnitude of +/- Gy acceleration during high AOA maneuvering was conducted.
      This preliminary mathematical model is able to predict the Gy load imposed on the
      head-neck complex of the pilot for a given set of flight maneuver parameters.
      RESULTS: The analysis predicts that at an AOA of 700 and with a roll rate of 100
      degrees x s(-1), the lateral G developed will be approximately 3.5 Gy. Increasing
      the roll rate increases the lateral G component: at 200 degrees x s(-1) the Gy,
      load is more than 6 Gy. CONCLUSIONS: There are serious potential implications of
      super agile maneuvers on the neck of the pilot. The G environment experienced by
      the pilot of super agile aircraft is increasingly multiaxial, involving +/- Gx,
      +/- Gy, and +/- Gz. The level of lateral G developed during these dynamic flight
      maneuvers should not be underestimated, as such G loads can potentially lead to
      neck injuries. While aircraft become ever more capable, a full understanding of
      the biodynamic effects on the pilot while exploiting the agility of the aircraft
      still needs to be developed.

PMID- 21853864
TI  - Technology and privacy: four key questions to ensure responsible research data
      capture.

PMID- 21853863
TI  - Successful trans-Atlantic air ambulance transfer of a patient supported by a bi
      ventricular assist device.
AB  - The ventricular assist device (VAD) is a hemodynamic support device that augments
      cardiac output for patients with severe ventricular dysfunction. With improved
      reliability and technological advances, the use of VADs to support patients is
      increasing. Many VAD-dependent patients ultimately require heart transplants that
      are only available in specialized centers, necessitating an interhospital
      transfer. To date there are few reports of long-distance fixed wing aeromedical
      transport of patients dependent on a VAD. Here we describe the successful
      transfer of a patient supported by a biventricular assist device (BiVAD) from
      Cambridge, UK, to Durham, NC, via fixed-wing jet aircraft. During this transfer,
      we observed hemodynamic alterations secondary to gravitational forces, which
      should be anticipated and may be mitigated with simple maneuvers. With high-level
      logistical planning and appropriate medical oversight, patients dependant on
      BiVADs can be safely transported by fixed wing aircraft over long distances.

PMID- 21853865
TI  - You're the flight surgeon: uveitis.

PMID- 21853866
TI  - This month in aerospace medicine history.

PMID- 21853867
TI  - [Effect of lipopolysaccharide and hypoxia on rat neutrophils in vitro].
AB  - The main aim of this study was to examine the role of lipopolysaccharide (LPS)
      and hypoxia on respiratory burst in rat neutrophils in vitro. Hypoxia (2% oxygen
      tension) inhibited respiratory burst of neutrophils in response to phorbol ester.
      Neutrophils treatment by LPS and hypoxia resulted in significant augmentation
      respiratory burst via NADPH oxidase activity in luminol chemiluminescence. This
      paper suggests that induction of iNOS was responsible for this effect.

PMID- 21853868
TI  - [Metformin--an inhibitor of early stages of protein glycation].
AB  - Nonenzymatic glycation of proteins is associated with the long-term diabetes
      complication. The aim of this work was to examine in vitro the infuence of
      metformin on glycated proteins formation by mass spectrometry (ESI/MS, LC/MS/MS)
      and spectrofluorimetric method. Obtained results suggest that metformin dose
      dependently inhibits early stage of Maillard reaction, although with the weaker
      potency than known glycation inhibitor aminoguanidine.

PMID- 21853869
TI  - The natriuretic peptide neurohormonal system modulation by vasopeptidase
      inhibitors--the novel therapeutical approach of hypertension treatment.
AB  - Vasopeptidase inhibitors (VPI) are a new promising class of drugs, that
      simultaneously inhibit Angiotensin - Converting Enzyme (ACE) and an enzyme
      Neutral Endopeptidase (NEP), that cleaves the natriuretic peptides. These drugs,
      such as omapatrilat, sampatrilat, fasidotrilat, by combined inhibition of ACE and
      degradation of natriuretic peptides and in turn by inhibiting the Renin -
      Angiotensin - Aldosterone system and potentiating the Natriuretic Peptide system
      and Kinin system should decrease the mortality rate in the group of patients with
      hypertension being not adequately controlled with ACE inhibitors. Thus, finding
      the new therapeutic strategy using drugs that act on the hormonal systems other
      than Renin - Angiotensin - Aldosterone system seems to be crucial. The aim of the
      study was to compare the molecular aspects of the conventional schemes that are
      being used in the antihypertension therapy to the new drugs from the
      vasopeptidase inhibitors group--with focusing on the natriuretic peptide system
      (NPS)--and, taking these considerations, making clues about therapeutical
      implications to reveal promising results in antihypertension treatment.

PMID- 21853870
TI  - [Diagnostic and prognostic value of atherosclerosis risk factors for predicting 1
      year outcome in patients with acute myocardial infarction and in patients with
      stable coronary artery disease receiving percutaneous transluminal coronary
      angioplasty].
AB  - Acute coronary syndrome as unstable angina and myocardial infarction are the
      clinical manifestations of destabilization of coronary atherosclerotic plaques.
      Optimal medical treatment (OMT) in addition to percutaneous transluminal coronary
      angioplasty (PTCA) with stent implantation decreased risk of cardiovascular
      mortality. This study was undertaken for searching the new cardiac risk factors
      to assess the clinical outcome in patients with acute myocardial infarct and
      stable angina receiving PTCA with stent implantation. The study included a sort
      group of 68 men, 26 with acute myocardial infarct (AMI), 29 with stable angina
      (SA) and 13 healthy men (K). Patients were treated with transluminal coronary
      angioplasty with stent implantation and continued standard pharmacological
      treatment. Measurements were taken at admission (baseline) and at 7 and 28 days
      (post-stress) after successful PTCA. Levels of IMA/ALB, hsCRP, CK, CK-MB,
      Troponin I, albumin, antioxidant potency parameters (FRAP, SH) and oxidative
      stress parameters (LOOH, IMA) were analyzed in serum from all patients. Our study
      demonstrated significantly higher serum IMA/ALB ratio in AMI group in comparison
      to SA group and controls. Categorized histogram revealed the highest IMA
      frequency in patients with angiographically confirmed stenosis compared to
      examined control subjects. IMA value tended to decrease in post-stress period but
      still remained the highest in AMI group as compared to controls. IMA
      concentrations were inversely correlated with heart ejection fraction, plasma
      antioxidant potential parameters (FRAP, SH) and positively correlated with CK and
      CKMB values. The comparative 1 year outcomes documented clinical failure in 19%
      vs. 52% of patients in AMI and SA groups respectively. The overweight and low
      antioxidant potency reached the statistical significance relevant to restenosis
      and cardiovascular events in SA group. Our data suggest that IMA levels in the
      course of myocardial ischemia treatment by PTCA may be useful as a discriminating
      marker for definition of the high risk group of patients with suspected
      cardiovascular complications.

PMID- 21853871
TI  - Intestinal mucosal mast cells and vagal nerve stimulation.
AB  - Vagal nerve stimulation, because of its involvement in the short- and long-term
      regulation of food intake, might become a useful tool in the treatment of
      obesity. However, both peripheral and central mechanisms of its action are still
      poorly understood. There is a strong evidence that intestinal mucosal mast cells
      play a general transduction role between the gastrointestinal tract and the
      central nervous system.

PMID- 21853872
TI  - [Small bowel diverticula as a cause of massive gastrointestinal bleeding--case
      report].
AB  - Jejunoileal diverticula are rare and often asymptomatic. However, they may lead
      to complications that manifest clinically with symptoms of acute abdomen.
      Diagnosis of complicated diverticular disease is difficult and depends on the
      result of surgical exploration. Resection and primary end-to-end anastomosis is
      the preferred method of treatment. The case of a 60-year old woman with a massive
      small bowel hemorrhage due to diverticular disease is described.

PMID- 21853873
TI  - [Abstract: case report of isolated metastasis to the spleen in a patient operated
      due to cancer of the sigmoid colon].
AB  - Isolated metastatic tumor of the spleen is rare and usually encompass the
      presence of neoplasmatic dissemination. The most frequent location of metastasis
      is right lobe of the liver, however solitaire secondary tumor to distant organ
      such as brain, lung, bone marrow or other might be discovered. This report refers
      to the 15th case of isolated intrasplenic metastasis from colon and rectal
      cancer. Splenectomy is a method of choice therefore may be justified in presence
      of isolated metastatic disease, because of low complication rate, providing
      potential long-term survival.

PMID- 21853874
TI  - The elemental composition of renal and ureteral stones determined with the energy
      dispersive X-ray fluorescence method (ED-XRF).
AB  - Many theories describe the lithogenesis within urinary tract. In addition, trace
      amounts of some heavy metals have been found in urinary calculi. However, their
      role in lithogenesis is still debated. Trace and heavy metals may be involved in
      induction of crystallization, depending on the relationships between metals and
      solutes able to crystallize in urine. Many papers have evaluated the elemental
      concentration of kidney stones, however there are still less data concerning the
      elemental composition of kidney and ureteral stones.

PMID- 21853875
TI  - [Localization and functions of c-kit positive cells in the urinary tract].
AB  - Interstitial cells of Cajal (ICCs) play an important role in the regulation of
      gut motility as they are responsible for the slow wave activity of smooth muscle.
      There is strong evidence that several subpopulations of ICC are present in the
      wall of the urinary tract. This review presents the currently available
      literature on the localization and proposed functions of interstitial cells of
      Cajal (ICC) in the urinary tract.

PMID- 21853876
TI  - [Social functioning adolescents with nocturnal enuresis problems].
AB  - Nocturnal enuresis co-exists with various emotional disturbances. Adolescents
      with bed-wetting problems often demonstrate a lowered self-esteem and self
      acceptance. Most adolescents who struggle with this unpleasant condition come
      from incomplete, dysfunctional families. The illness does not allow the teenager
      to function comfortably in society and it may lead to increased emotional
      problems in the psyche of an adolescent person. Sickness does not allow free
      social functioning teenager and it can be problems in emotive sphere reason of
      deepening growing person.

PMID- 21853877
TI  - Histological changes in seminiferous epithelium in testis of male mice induced by
      injection of lipopolysaccharide (LPS).
AB  - LPS induces an inflammatory state which kmitates septic shock and which involves
      also an organ which is immunologically advantageous, namely testicle. Within an
      area of a gonad, this manifests itself by histological changes in the structure
      of germinal epithelium. The blockages of cell divisions lead also to disorders in
      the proportions of cells in particular stages of spermatogenesis, degeneration of
      germinal epithelium and the decrease of the number of spermatozoa in the lumen of
      seminiferous tubules. Maximal changes are observed on the 15th day of
      inflammatory state and they are reversible with the process of the animals'
      restoration to health. The number of macrophages rises quickly in Leydig's glands
      and it remains constant till the 28th day after the administration of LPS.

PMID- 21853878
TI  - [Cervical vertebral column--anatomy, fractures, treatment].
AB  - The paper deals with anatomy of human cervical spine. It shows close relation
      between knowledge on the normal structure and methods of treatment of different
      kinds of spine injuries. It describes detailed anatomy and mechanical features of
      cervical vertebral column, including the structure of distinct vertebrae, their
      joints and arrangement of muscles. It reviews also historical methods of
      treatment of fractures in this region considering current methods.

PMID- 21853879
TI  - [Anatomical aspects and procedures in plateau fractures].
AB  - The paper deals with anatomy of proximal extremity of tibia and specially focuses
      on the problem of its fractures and methodology of orthopedic procedures.
      Fractures of tibial plateaus are mostly intracapsular and may cause long-lasting
      consequences. They account for about 7% of all fractures in the limbs and affect
      both young and adult individuals. Current classification and descriptions of
      fractures, methods of diagnostics and treatment are also given.

PMID- 21853880
TI  - [Research on viral hepatitic C treatment].

PMID- 21853881
TI  - [Evaluation of pharmacokinetic drug-drug-interactions. Critical considerations of
      the relevance of pharmacokinetic drug-drug interactions of proton pump inhibitors
      in self medication].
AB  - Mechanisms and evaluation of pharmacokinetic drug interactions are discussed in
      general, including mechanisms beyond the hepatic phase-I reactions, and
      especially for the example of proton pump inhibitors (PPI), preferentially
      omeprazole. Particular attention is paid to the use of PPI as self-prescribed
      drugs. The sequelae of pharmacokinetic drug interactions can be serious. However,
      only the evidence of clinical consequences will convert such an interaction from
      a laboratory finding into a possible adverse effect. Without this, interacting
      drugs can still be co-administered if the specific characteristics of the
      concerned drugs, quantitative aspects of the interaction, and especially severity
      and frequency of possible clinical correlates are taken into consideration. It is
      encouraging that the laboratory findings reported for the PPI--in vitro or ex
      vivo from volunteer studies--have hardly found equivalents in clinical
      consequences. As of today, this is also true of the widely discussed interaction
      with clopidogrel. Regarding the safety of use of PPI as self-prescribed drugs, it
      also needs to be emphasized that a sizable number of interactions reported for
      omeprazole and/or pantoprazole were observed at higher dose levels than the 20 mg
      licensed for self medication. In conjunction with the temporal limitation of PPI
      self-prescription (14 days), it can be expected that pharmacokinetic drug
      interactions will generally be no critical factor in the usage of PPI in self
      medication. However clinically relevant interactions can occur, e.g. when PPI are
      combined with extracts from St. John's wort, methotrexat or some inhibitors of
      HIV-protease with pH-dependent absorption.

PMID- 21853882
TI  - [Current standards in the treatment of breast cancer].
AB  - Breast cancer is the most frequent malignoma in female individuals: more than 10
      out 100 females suffer from the disease. The understanding of breast cancer as a
      primarily local disease has undergone a fundamental change in the last few
      decades. While throughout most of the previous century breast cancer was still
      mainly conceived of as a predominantly local disease, the radical nature of
      surgery can now be reduced to a minimum by the use of breast conserving
      procedures and axillary sentinel lymph node excision. The systemic use of
      cytostatic and endocrine therapeutic modalities has simultaneously provided a
      major overall survival benefit for patients treated in accordance with current
      therapeutic standards. The multidisciplinary treatment challenge of breast cancer
      comprises nowadays surgery, systemic treatment and radiotherapy and aims to a
      more individualized therapy.

PMID- 21853884
TI  - The driving force in research.

PMID- 21853883
TI  - [The updated recommendations of the US Institute of Medicine (IOM) on the intake
      of vitamin D. A critical appraisal].
AB  - In the context of optimization long-term health, the research activities on the
      secosteroid vitamin D have become an important field of discourse. The discussion
      has focused on whether and, if so, to what extent, vitamin D might contribute to
      the prevention of various disorders, e.g. infections, autoimmune diseases,
      several types of cancer and diabetes mellitus type 2. Accordingly, in the recent
      past many voices were raised asking for a significant elevation of the
      recommended vitamin D intake. In November 2010 the decisive US Food and Nutrition
      Board (FNB) of the Institute of Medicine (IOM) revised the dietary reference
      intake for vitamin D. The updated recommendations were awaited eagerly and have
      now been published. This article discusses the new recommendation and comments on
      aspects which have to be considered critically.

PMID- 21853885
TI  - The complexities of using grounded theory.

PMID- 21853886
TI  - Navigating the grounded theory terrain. Part 1.
AB  - AIM: The decision to use grounded theory is not an easy one and this article aims
      to illustrate and explore the methodological complexity and decision-making
      process. It explores the decision making of one researcher in the first two years
      of a grounded theory PhD study looking at the psychosocial training needs of
      nurses and healthcare assistants working with people with dementia in residential
      care. It aims to map out three different approaches to grounded theory: classic,
      Straussian and constructivist. BACKGROUND: In nursing research, grounded theory
      is often referred to but it is not always well understood. This confusion is due
      in part to the history of grounded theory methodology, which is one of
      development and divergent approaches. Common elements across grounded theory
      approaches are briefly outlined, along with the key differences of the divergent
      approaches. DATA SOURCES: Methodological literature pertaining to the three
      chosen grounded theory approaches is considered and presented to illustrate the
      options and support the choice made. DISCUSSION: The process of deciding on
      classical grounded theory as the version best suited to this research is
      presented. The methodological and personal factors that directed the decision are
      outlined. The relative strengths of Straussian and constructivist grounded
      theories are reviewed. CONCLUSION: All three grounded theory approaches
      considered offer the researcher a structured, rigorous methodology, but
      researchers need to understand their choices and make those choices based on a
      range of methodological and personal factors. In the second article, the final
      methodological decision will be outlined and its research application described.

PMID- 21853887
TI  - Applying a contemporary grounded theory methodology.
AB  - AIM: The aim of this paper is to discuss the application of a contemporary
      grounded theory methodology to a research project exploring the experiences of
      students studying for a degree in midwifery. BACKGROUND: Grounded theory is a
      qualitative research approach developed by Glaser and Strauss in the 1950s but
      the methodology for this study was modelled on Clarke's (2005) approach and was
      underpinned by a symbolic interactionist theoretical perspective, post
      structuralist theories of Michel Foucault and a constructionist epistemology.
      REVIEW METHODS: The study participants were 19 midwifery students completing
      their final placement. Data were collected through individual in-depth interviews
      and participant observation, and analysed using the grounded theory analysis
      techniques of coding, constant comparative analysis and theoretical sampling, as
      well as situational maps. The analysis focused on social action and interaction
      and the operation of power in the students' environment. The social process in
      which the students were involved, as well as the actors and discourses that
      affected the students' competency development, were highlighted. CONCLUSION: The
      methodology allowed a thorough exploration of the students' experiences of
      achieving competency. However, some difficulties were encountered. One of the
      major issues related to the understanding and application of complex sociological
      theories that challenged positivist notions of truth and power. Furthermore, the
      mapping processes were complex. Despite these minor challenges, the authors
      recommend applying this methodology to other similar research projects.

PMID- 21853888
TI  - Rigour and grounded theory.
AB  - AIM: This paper explores ways to enhance and demonstrate rigour in a grounded
      theory study. BACKGROUND: Grounded theory is sometimes criticised for a lack of
      rigour. Beck (1993) identified credibility, auditability and fittingness as the
      main standards of rigour for qualitative research methods. These criteria were
      evaluated for applicability to a Straussian grounded theory study and expanded or
      refocused where necessary. The author uses a Straussian grounded theory study
      (Cooney, In press) to examine how the revised criteria can be applied when
      conducting a grounded theory study. REVIEW METHODS: Strauss and Corbin (1998b)
      criteria for judging the adequacy of a grounded theory were examined in the
      context of the wider literature examining rigour in qualitative research studies
      in general and grounded theory studies in particular. A literature search for
      'rigour' and 'grounded theory' was carried out to support this analysis.
      CONCLUSION: Criteria are suggested for enhancing and demonstrating the rigour of
      a Straussian grounded theory study. These include: cross-checking emerging
      concepts against participants' meanings, asking experts if the theory 'fit' their
      experiences, and recording detailed memos outlining all analytical and sampling
      decisions. IMPLICATIONS FOR RESEARCH PRACTICE: The criteria identified have been
      expressed as questions to enable novice researchers to audit the extent to which
      they are demonstrating rigour when writing up their studies. However, it should
      not be forgotten that rigour is built into the grounded theory method through the
      inductive-deductive cycle of theory generation. Care in applying the grounded
      theory methodology correctly is the single most important factor in ensuring
      rigour.

PMID- 21853889
TI  - Responding to reviewers' comments as part of writing for publication.
AB  - AIMS: The aim of this paper is to provide a resource for authors to help them in
      getting their work published. The focus is on dealing with, and responding to,
      the comments of reviewers. BACKGROUND: The importance to research of nurses
      writing for publication is widely acknowledged. However, a number of significant
      barriers to nurses actively engaging in this form of dissemination has been
      identified. Ways in which nurses can avoid the pitfalls that would make their
      manuscripts more likely to be rejected have been the subjects of published
      articles. Significantly less attention has been devoted to providing authors with
      methods to assist them in responding when their manuscripts are rejected or major
      revisions are requested. DISCUSSION: This article provides a brief overview of
      the process of editorial review. It offers a practical but structured approach to
      responding to reviewers' comments when undertaking major revisions and to
      preparing a rejected manuscript for resubmission to another journal. CONCLUSION:
      Authors frequently respond negatively to reviewers' comments and this may result
      in their being dissuaded from writing for publication. A structured approach to
      dealing with reviewers' comments may help nurses in making the requested
      revisions and increase their chances of publication. IMPLICATIONS FOR RESEARCH:
      The publication of research findings and other scholarly work are important for
      the professional advancement of nursing. Strategies to overcome the barriers to
      writing for publication are essential to achieving this goal. Helping authors to
      respond positively to reviewer critique and to make the necessary changes are
      important steps in this process.

PMID- 21853890
TI  - Methodological and ethical challenges in investigating the safety of medication
      administration.
AB  - AIM: The aim of this article is to highlight some of the methodological and
      ethical challenges that the researcher faced when conducting a study of the
      safety of medication administration. BACKGROUND: Investigating a sensitive topic,
      such as the safety of medication administration, can be methodologically
      demanding, time-consuming and ethically challenging. Moreover, it can be
      particularly difficult to balance methodological with ethical and legal
      challenges. This article presents the considerations involved in the sampling,
      recruitment and ethical issues related to participants' involvement in a
      medication safety study. DATA SOURCES: The article draws on the methodological
      and ethical approaches related to one qualitative study that investigated the
      nurse's views of the organisational contributions toward the safety of medication
      administration in adult critical care. The study was completed in 2009.
      DISCUSSION: The study used a questionnaire to recruit the paticipants and this
      gave the researcher the advantage of being able to select critical care nurses
      from particular backgrounds, enriching the views and perspectives relating to the
      topic under investigation. Approaching the participants for 'expert' opinions,
      rather than 'error-makers', helped to established early rapport with the
      participants. Research rigour and data trustworthiness were demonstrated by
      several operational techniques, including providing a detailed account and
      justification for the research process. CONCLUSION: Research into patient safety
      may have particular methodological and ethical challenges and therefore needs an
      appropriate research approach to balance practicality, the participants'
      integrity and research rigour. IMPLICATIONS FOR PRACTICE AND RESEARCH It is
      anticipated that this approach will provide an insight into some challenges that
      may arise in conducting patient safety research, providing a useful guide for
      others to consider in their future research.

PMID- 21853891
TI  - Assessing the effect of a complex psychosocial intervention: a methodological
      note on determining measurement intervals.
AB  - AIM: Guidelines describing how to carry out a randomised controlled trial (RCT)
      provide no advice concerning when to measure an intervention effect. Possibly as
      a result, most papers give no rationales for the time frames chosen for data
      collection. This paper discusses four general strategies to identify when to
      collect data. Furthermore, an additional individual strategy concerning the
      current German young carers project is presented. BACKGROUND: The first German
      young carers project is being implemented and evaluated in a pilot study's RCT.
      Organisational difficulties as well as problems accessing the field led to a
      delay in the research and ended with a change to the overall timeframe for data
      assessment. This process resulted in a discussion by the research team about
      whether the shorter timeframe would lead to biased data. DISCUSSION: The authors
      discuss how they reviewed the literature and decided how to determine the best
      point to conduct follow ups with their study participants. CONCLUSION: The
      authors conclude that the standard three-month intervals used in RCTs are not
      necessarily applicable to psychosocial interventions and researchers should
      determine more appropriate intervals where possible.

PMID- 21853893
TI  - Six stages of doctoral study: a new model for PhD students.

PMID- 21853892
TI  - Demystifying nursing research terminology. Part 1.
AB  - AIM: This article aims to provide clear explanations of the research approaches
      available for nursing research. BACKGROUND: There are numerous research
      approaches available to the nurse researcher. There is also some ambiguity in the
      literature in relation to research terminology and this often leads to confusion
      about which approach to adopt. DATA SOURCES: A review of the available and most
      up-to-date literature. DISCUSSION: The most commonly adopted approaches in
      nursing research are described and discussed. CONCLUSION: This article explains
      the research paradigms and the rationales for choosing particular paradigms while
      part two will provide an explanation of the methodological options available to
      the researcher. A table is included that summarises the key information related
      to each paradigm. IMPLICATIONS FOR PRACTICE/RESEARCH: These articles will be
      particularly useful for the novice researcher or for the doctoral student.

PMID- 21853894
TI  - [The effectiveness of the vertebroplasty in the treatment of the osteoporotic
      vertebral fractures].
AB  - We describe the use of vertebroplasty as an effective method to treat
      osteoporotic vertebral changes. Scant reports in the literature of national
      expertise and low penetration of this method in Poland has led the author to
      conduct their own research demonstrating the effectiveness of the method on the
      basis of treatments performed in Spine Surgery, Oncology Orthopedics and
      Traumatology Department W. Dega at University Hospital Poznan, Poland and to
      collect literature describing the topic. 47 patients were enrolled unambiguously
      confirmed osteoporosis (T score <2.5) on the basis of Dual energy X-ray
      absorptiometry (DXA) of the femoral bone. Clinical and radiological examination
      confirmed the compression fracture of the vertebrae, which was not effectively
      treated conservatively for at least 6 weeks. The pain was objectified as a major
      factor in the deteriorating quality of life using an analog scale for assessing
      pain VAS. To evaluate other clinical indices there were used: scale of disability
      due to back pain named Ostwestry and scale for assessing quality of life RAND-36
      before surgery and long-term testing of the period from 2 months to 4 years after
      vertebroplasty. On the basis of a comprehensive radiological assessment of the
      vertebral height and the angle formed by lines of adjacent vertebral median--the
      angle of lordosis and kyphosis. It was observed a significant reduction in pain
      of patients, improving quality of life and disability in the testing of the
      vertebroplasty. Also it was observed a slight reduction of the collapsed
      vertebrae in some patients immediately after vertebroplasty. Proved the
      efficiency of the vertebroplasty in preventing further collapsing of futher
      fractured vertebrae.

PMID- 21853895
TI  - [The utility of monoclonal antibodies in the diagnostic work-up of spinal
      metastases].
AB  - The skeletal system is the third most frequent (after lungs and liver) seat of
      metastases, and metastatic tumours are the most common bone malignancies. The
      diagnostic work-up of spinal metastases begins with the identification of the
      primary neoplastic site. Histological analysis confirms the final diagnosis. The
      work-up of bony metastases poses considerable difficulty and requires the
      collaboration of a number of specialists. Historical paraffin-embedded tissue
      samples were subjected to a routine procedure for the preparation of histology
      specimens. All specimens were independently reassessed by two diagnosticians. The
      samples of metastatic tumours of 57 patients whose primary tumour sites had not
      been identified were subjected to an immunohistochemical analysis based on
      monoclonal antibodies and assays for antigens associated with tumours most often
      producing bony metastases, i.e.:: PSA, thyreoglobulin, villin, cytokeratin 7,
      cytokeratin 8, cytokeratin 17, cytokeratin 18, cytokeratin 19, cytokeratin 20, CD
      38, oestrogen and progesterone and Vimentin, LCA, HMB-45 and S-100. The
      monoclonal antibodies and assays were shown to be useful aids for the
      identification of the histology and location of the primary tumour in patients in
      whom routine histological assessments had failed to determine the histological
      type of tumour. In many cases, effective immunohistochemical work-up can
      contribute to halting the progression of the tumour by enabling qualification for
      appropriate surgical and oncological treatment.

PMID- 21853896
TI  - [Total hip replacement in treatment of patients with deformity of the hip caused
      by ankylosing spondylitis].
AB  - BACKGROUND: Total hip replacement (THR) is at present an accepted treatment in
      patients with severe deformity of the hip caused by advanced ankylosing
      spondylitis. The aim of this paper is to evaluate the results of THR in patients
      suffering from ankylosing spondylitis, operated from 1987 to 2007 at the
      Orthopaedic and Traumatologic Department of Poznan University of Medical
      Sciences. Material. Material included 26 patients, 2 females and 24 males, on
      whom 34 THR were performed, lateral approach was used in all cases. At the time
      of operation, the age of patients ranged from 27 to 77 years (mean 57). Follow-up
      ranged from 3 to 21 years (mean 10.5 years). The operative treatment was a
      multistage process (during one operation only one joint was replaced). Cemented
      totalhip arthroplasty was used during 16 of the THR, 17 of them were cementless
      and 1 as a hybrid. METHOD: The patients were clinically and radiologically
      evaluated preoperatively, postoperatively, and at final examination. The clinical
      state was evaluated with Harris hip score and WOMAC scale. We based our
      radiological examination on Hip Society system. RESULTS: The average preoperative
      Harris score for the group of patients was 27.3, WOMAC score 78.5. After an
      average of 10 years follow-up all hips and knees were considered excellent, with
      average Harris score of 91.4, WOMAC Score of 5.0. All patients had increased
      function and decreased pain. The radiograms of all patients revealed that the
      acetabular and femoral components were correctly positioned with no radiographic
      evidence of loosening in the last examination. No ectopic ossification
      concentrations were found. CONCLUSION: Clinical and radiological evaluation of
      our material showed that total hip replacement in the treatment of severe
      deformity of the hip caused by advanced ankylosing spondylitis allows regaining
      good lower limb function, which helps the patients staying less dependant on the
      surrounding environment. Ectopic ossification is not the clinical problem during
      THR in patients who suffer from spondylytis deformans.

PMID- 21853897
TI  - [Reactions of bone tissue around the ABG II stem].
AB  - The uncemented total hip replacement became a standard in treatment of the severe
      hip osteoarthritis. Its long term efficiency is based on the correct
      osteointegration which depends on the adequate implantation. Material. The study
      group consisted of 49 patients (52 hips) following total hip replacement with ABG
      II stem and Trident PSL cup. The follow-up ranged between 6 months and 2 years.
      METHODS: In each case the Harris hip score was performed and high resolution x
      rays were taken. On X-ray the fit and position of the stem, linear osteolysis
      around the stem and bone atrophy at the greater trochanter were evaluated.
      Results. The mean HHS at the last follow up was 90.4 (50-99). The mean angle of
      the stem position was 2.9 varus. The mean fit index was was 0.75. The significant
      correlation was found between the fit index and the varus stem position angle.
      The linear osteolysis surrounding the stemin the 1st Gruen zone was found in 70%
      of cases. The phenomenon of the linear radiolucenecy surrounded by linear
      densification was found in the 76% of cases. Bone atrophy at the greater
      trochanter was found in the 42% of cases. Conclusions. The use of ABG II stems
      provided very good clinical results. The stem has a tendency to a varus position,
      which seems to be connected with the use of the too small stems. Specific
      radiographic observations create a need of futher follow-up, but existed without
      the influence on the clinical results.

PMID- 21853898
TI  - [Acute, haematogenous arthritis of the hip in children--treatment and long follow
      up assessment].
AB  - BACKGROUND: This is a retrospective study of 15 cases of acute septic arthritis
      of the hip in older children treated from 1995 to 2007. MATERIALS AND METHODS:
      All treated children were over 2 years old. The average follow-up period was 7
      years (2-16 years). Among patients, there were 11 males and 4 females. None of
      them had bilateral disease presentation. All cases met the diagnostic criteria
      including bacteriological results, clinical or radiographic changes. The average
      duration of symptoms before admission to the hospital was 6,5 days (1-35 days).
      Pain in affected hip was observed in all patients, other symptoms were: limited
      range of motion (12 patients), fever (14 patients), abdominal or thigh pain (4
      patients). Only one-third of the patients had a leukocyte count of over 12
      000/mm3, the erythrocyte sedimentation rate was elevated in all cases--average
      80/125, CRP ranged from 3.1-205 mg/l. 13 cases underwent emergency arthrotomy and
      debridement, two patients received only intravenous antibiotic treatment without
      arthrotomy. Pathogens had been isolated from blood only in 3 cases (20%), from
      arthrocentesis fluid in 8 patients (62%). Staphylococcus aureus was the most
      common pathogen (54%). RESULTS: All patients had been succesfully treated. 10 of
      them had good result, 3 satisfactory and 2 unsatisfactory according to Kiepurska
      criteria. CONCLUSIONS: A delay in definite treatment was the important factor
      associated with poor prognosis. One patient who received only intravenous
      antibiotic treatment showed satisfactory result - early diagnosis and significant
      response to antibiotics contributed to this favorable outcome.

PMID- 21853899
TI  - [Clinical versus radiological mid-term results of total knee arthroplasty for
      degenerative arthritis of the knee].
AB  - Total knee arthroplasty (TKA) is widely accepted method for treatment of severe
      osteoarthritis. The aim of this paper was to retrospectively review patients
      operated in our institution with total condylar knee arthroplasty due to
      osteoarthritis and assess clinical and radiological results of this procedure.
      All patients treated with TKA between 1998 and 2001 were reviewed, those with
      diagnosis of rheumatoid arthritis were excluded from the study. One hundred and
      one TKA in 68 patients were studied. WOMAC protocol and KSS (Knee Society Score)
      were used to evaluate patients clinically, and KSS alone for radiological
      analysis. Bone-implant interface has been studied, position of the implants and
      mechanical axis of the limb both pre- and postoperatively. Excellent and good
      results were achieved in 89% of TKA. Subjective self-assessment was usually worse
      than objective one. Radiolucency was found in 16 cases (more often around tibial
      component than the femoral one), usually without clinical symptoms of the
      loosening. An accurate alignment within the range of 3 to 9 degrees valgus has
      been found in 68% of the knees. Subjective scores were worse than objective
      clinical assessment. The clinical score was higher than radiological one. The
      tendency to varus tibial implant fixation was observed. Suboptimal implantation
      has not led to implant loosening in mid-term results.

PMID- 21853900
TI  - [Final results of the operatively treated femoral neck fractures in children and
      adolescents].
AB  - BACKGROUND: Femoral neck fractures in children occur 130 times more seldom than
      in adult's population. According to specific vascularisation the most common
      complication is avascular necrosis (AVN) of the femoral head. Purpose of the
      study was the treatment's results analysis of the 15 children and adolescent's
      femoral neck fractures. METHODS: 15 patients at a mean age of 12.7 years (5-17
      years) presenting with femoral neck fractures were analyzed. On the pre- and
      postoperatively X-rays we have determined the type of fracture in Delbet
      classification and compared femoral-neck angle with the healthy side. In the
      final clinical examination ROM, the equality of leg's length and quality of
      walking were checked. The results were determined in the Harris hip score and
      Ratliff score. We divided the patients into 3 groups that depended on the time of
      surgery: 1) operated up to 24 hours after injury (6 patients), 2) 24-72 hours
      post fracture (5), 3) after 72 hours (4). RESULTS: 10 fractures were classified
      to type 2, 3 fractures to type 3 according to Delbet scale (X-rays of 2 patients
      are missed). The final outcome after 7-163 months (57 on average) could be
      precised at 13 patients. Significant ROM decreasing was confirmed in 4 patients.
      The highest restriction was noticed in internal rotation (on average 14 degrees
      comparing with the healthy side). Other motions were slightly restricted.
      Inequality of limb's length amounted 0.5 cm on average. The average Harris hip
      score amounted 92.58 (76-100). The final results were assessed as very good at 8
      patients, good at 4 and moderate in 1 patient. We haven't noticed bad results.
      AVN were suspected in 3 patients, 2 of them were scintigraphically confirmed.
      CONCLUSIONS: In order to avoid AVN the most important thing is an early (up to 24
      hours since the injury) anatomic reposition and proper bone fragments
      stabilization.

PMID- 21853901
TI  - [Results of treatment of the intercondylar eminence of tibia in children].
AB  - Fracture of the tibial eminence in children is a condition in which there is no
      widely accepted and approved therapeutic scheme. The greatest divergence of
      treatment options concerns type II according to Mayers and McKeever
      classification. Described therapeutic options range from cast immobilisation of
      the lower extremity without attempt of closed reduction to open reduction with
      internal fixation. Paper shows the results of treatment of tibial emienence
      fractures in children treated at our institution. Cohort of patients consists of
      21 children at age 7 to 16 years of age (mean 12.2 years). There were three cases
      of type I, five cases of type II and thirteen cases of type III fracture
      according to Mayers and McKeever classification. Operatively 16 patients were
      treated with type II and III fracture, and the rest of them were treated
      nonoperatively. Open reduction and internal fixation was performed according to
      modified technique described in 1937 by H. Lee. The results were evaluated by X
      ray, clinical examination of stability and range of motion of the affected knee
      and by subjective clinical outcome with use of modified Lysholm knee scale. All
      patients treated operatively presented very good and good clinical outcome.
      Nonoperatively treated patients was a small and no homogenous group. Results of
      treatment ranged from very good to poor. Worse outcomes were associated with
      additional injuries to the affected knee (poor result in patient with type II
      fracture) and qualification for the conservative treatment in patient with type
      III fracture.

PMID- 21853902
TI  - [The efficacy assessment of cuboid and medial cuneiform bone wedge ostetomy in
      the treatment of metatarsus adductus].
AB  - Metatarsus adductus is usually a morphologic feature of the clubfoot or occurs as
      an isolated defect. Such deformation causes shortening of the medial foot column
      and lengthening of the lateral. The purpose of the study is a retrospective
      evaluation of long-term therapeutic effects in a group of patients, who underwent
      closing wedge cuboid osteotomy and opening wedge medial cuneiform osteotomy.
      Surgery was performed in 19 persons, procedure was applied to 26 feet, of which 3
      presented congenital metatarsus adductus and 23 presented recurrent clubfoot.
      During ostoetomy we performed additional corrective procedures on soft tissues.
      Foot and gait deformation, pain associated with activities, presence of calluses
      on the lateral plantar surface of the foot, difficulty in footwear were evaluated
      before and after surgery on clinical examination. The pre- and post operative X
      rays were used to determine: in AP view the Kite's angle and the angle between
      the calcaneal bone and the 5th metatarsalbone (forefoot adduction evaluation), in
      lateral view the Kite's angle, the angle between the calcaneal bone and the 1st
      metatarsal bone (forefoot supination evaluation) and the angle between the talus
      and the 1st metatarsal bone (cavus evaluation). An early recurrence of the
      deformation after the removal of wire fixation occurred in 2 patients. Late
      complications taking the form of adduction and supination of the forefoot
      occurred in 5 cases. In general recurrences of adduction of the metatarsus
      occurred in 27 % operated feet. Radiographic evaluation proved a significant
      statistical effect of the "plus-minus" osteotomy limited to the reduction of the
      adduction angle of the forefoot and not affect improvement of the supination of
      the forefoot and the foot excavation.

PMID- 21853903
TI  - [Quality of life in cerebral palsy children treated with intrathecal baclofen
      pump implantation in parents' opinion].
AB  - INTRODUCTION: Most common disorder in patients with cerebral palsy (CP) is
      spasticity. It is a result of non-progressing damage of Upper Motor Neuron
      system, causing imbalance signals, and consequently increasing muscle activity.
      Spasticity decreased activity of daily living of the patient and their
      caregivers. It may cause many medical and social problems. Baclofen is a
      synthetic analog of gamma-aminobutryacid, admistrated in intrathecal space by
      pump. It inhibits both monosynaptical and polisynaptical spinal reflexes. First
      time baclofen pump (ITB) were applied by Penn and Kroin in 1984 to treat
      spasticity. ITB is indicated in severe children cerebral palsy, especially in
      tetraparesis. The purpose of this study is attempt for objective and subjective
      evaluation of the quality of life after implantation of ITB. MATERIAL AND
      METHODS: In this research data of 161 children were analyzed with spastic
      tetraparesis (GMFCS V). Evaluation was based on an analysis of the quantity of
      additional surgical procedures before and after ITB implantation. Subjective
      assessment was made using questionnaires addressed to parents on fundamental
      aspects of everyday activities and quality of life after implantation of ITB.
      RESULTS. The average age AT the time of surgery was 12 year and 2 months (SD
      4.7). The average follow up was 3 years and 2 months (SD 2.4). During ITB
      implantation additional surgical procedure were performed in 43% of Children.
      During the next scheduled ITB pump exchange indication to addictional surgical
      procedure was reduced to 20%. The average questionnaire score was 13 points (0-16
      max.). Fifty eight percents of caregivers of children who had any kind of device
      related complication scored with average score 13.5. CONCLUSION: 1) ITB
      implantation in the treatment of children with severe CP improves their quality
      of life. 2) Indication to perform surgical procedures were reduced in patients
      treated with ITB. 3) ITB implantation correlates with the high level of
      caregivers satisfaction as the potential for improvements, however one have to
      think about the complication.

PMID- 21853904
TI  - [Influence of tendon surgery training on the quality of the suture].
AB  - Injuries of flexor tendons are one of the most common injuries that need surgical
      treatment at emergency room. Technique and quality of the surgery was performed
      are two factors of the utmost importance. The aim of the study was to determine
      influence of basic surgical training on the quality of suture. Research was
      divided into four surgical sessions which were held each once a week. Sutures
      were put by three medical students. Material that was used were deep flexor
      tendons dissected from fresh pig's legs. Sessions 1st, 2nd and 4th were preceded
      by training done by experienced surgeon. During study 90 modified-Kessler sutures
      without additional running suture were made. Breaking strength was assesed by
      tensile machine (INSTRON 4481). Time of each suture was also recorded. Outcomes
      were analyzed by tests: ANOVA and post-hoc LSD tests. Time significantly dropped
      by 64% after the first session and was held on the same level. Strength of
      sutures rises in each session preceded by training. There was statistically
      significant difference between session 1 (mean 13.58; SD 9.86N) and 2nd (mean
      42.69; SD 9.27N) and 3rd (mean 38.42; SD 12.28N) and 4th (mean 57.12; SD 12.78N).
      Conclusions. Time of procedure significantly dropped after first teaching course
      and was held on the same level despite further training. Breaking strength rise
      in every session that was preceded by teaching course.

PMID- 21853905
TI  - [Methods of rapid prototyping in preoperative planning in musculoskeletal
      reconstructive surgery].
AB  - Rapid Prototyping and CT based 3D modelling implementation in orthopaedic
      reconstructive surgery is presented in the article. Bone models rendered in SLS
      (Selective Laser Sintering) were used in pre-operative planning. Physical models
      were made based on imaging data obtained in standard CT scans. Better pre
      planning, surgical team preparation and an insight into possible difficulties are
      the obvious advantage of the method as well as resulting reduced complication
      rate. Its clinical applicability was confirmed during surgical procedures.

PMID- 21853906
TI  - [Recent update on tennis elbow pathomechanics].
AB  - There is still some disagreement about which anatomical structures are involved
      in tennis elbow pain, as well as its pathomechanics. In many papers attempting to
      explain the tennis elbow pathomechanics, most often the authors would point out
      to degenerative changes (of various background), which could be inflammatory in
      nature only initially. It is believed that the chronic patients are the most
      problematic cases, the origin of their ailment probably caused by many factors.

PMID- 21853907
TI  - [Epicondylitis--diagnostics and treatment].
AB  - Shortcomings of tennis elbow treatment have raised medical interest in
      pathomechanics of this condition. In 2009, a new theoretic model was proposed,
      one that has integrated the current knowledge about tennis elbow pathophysiology,
      with aim to improve the effectiveness of therapeutic methods. It was suggested
      that tennis elbow patients should be grouped by severity of local tendon
      pathology, change in pain perception and degree of motor apparatus malfunction
      when deciding on the most suitable treatment method or when designing scientific
      research on the subject. It is believed that by employing detailed diagnostics of
      these lesions (either separate or clustered) in order to confirm or eliminate
      their presence, the effectiveness of their treatment should increase.

PMID- 21853908
TI  - [Results of operative treatment thoraco-lumbar fractures by posterior lumbar
      interbody fusion, Daniaux reconstruction or combination of both methods].
AB  - The aim of the study was to compare clinical and radiological results of
      treatment thoraco-lumbar spine fractures by short segment transpedicular
      stabilization accompanied by three techniques of reconstruction: posterior lumbar
      interbody fusion, vertebral body Daniaux reconstruction and combination of both
      methods. AO system was used to classify the fractures. Frankel's grade system was
      used for assessment of neurological deficit on admission and subsequently in the
      postoperative and follow-up period. The height of the fractured vertebral body
      and angle of segmental kyphotic deformation was measured on lateral X-ray pre-
      and post-operatively and at last follow-up. To the retrospective analysis we
      included 167 patients operated in the Orthopaedic and Traumatology Department,
      Medical University of Lublin in years 1998-2007. Posterior lumbar interbody
      fusion was performed in 69 patients (41%), isolated vertebral body Daniaux
      reconstruction in 82 patients (49%) and combination of both methods was performed
      in 16 patients (10%). The follow-up period has ranged from 3 to 13 years (mean
      6.9 years). The most common type of the fracture was a B type (104 patients 
      62%), followed by type A (43 patients--26%), and type C (20--patients 12%). The
      neurological deficit was present in 80 patients. The postoperative neurological
      improvement was noticed in 37 patients (46%), whereas in 46 patients (54%)
      neurological status has not changed after the treatment. From 87 patients without
      neurological symptoms, we observed postoperatively contemporary neurological
      complications in 11 (12.6%) cases. The biggest correction of fractured vertebral
      height (mean 0.15) and correction of segmental kyphotic deformity (mean 6.3
      degrees) we have noticed in the group of isolated vertebralbody Daniaux
      reconstruction with use of bone grafts. However in every group of patients we
      observed significant loss of correction during follow-up period. At the latest
      follow-up assessment there were no differences in vertebral body height of
      segmental kyphotic deformation between the analyzed groups of patients. None of
      analyzed methods of treatment: posterior lumbar interbody fusion, vertebral body
      Daniaux reconstruction or combination of these methods did not protect from
      recurrence of kyphotic deformity.

PMID- 21853909
TI  - [Effectiveness of botulinum toxin in diminishing lower limbs spasticity in
      children with diplegic form of cerebral palsy].
AB  - INTRODUCTION: Intramuscular injection of botulinum toxine (BTX-A) is important
      method of spasticity treatment in cerebral palsy (CP) children. RESEARCH AND
      METHOD: Research group consisted of 60 children, aged 2-8 with diagnosed diplegic
      form of CP treated in years 2002-2004 with BTX-A. Research was conducted before
      and approximately four weeks and three months after injections. Third examination
      was performed just before another injection. Patients on the functional level II
      to IV according to GMFCS were qualified for study. Level of spasticity, range of
      motion (ROM) and course of rehabilitation were assessed each time. Effectiveness
      of therapy was also studied based of parent's opinions. RESEARCH OUTCOMES:
      According to GMFCS 14 children (23.3%) were classified to level II, 29 children
      (48.4%) to level III and 17 (28.3%) to level IV. In all children spasticity
      decreased. ROM measured by fast and slow movement in hip, knee and ankle joints
      increased significantly. During treatment Reimers index was bilaterally normal in
      38%, unilaterally in 11% of patients. Index value was normalized in 7.7% of
      patients. Therapeutic effect of applied treatment method was observed by 96.7% of
      parents. No side effects have been observed. CONCLUSIONS: By means of BTX-A
      injections temporary reduction of spasticity in selected muscle groups can be
      achieved. Injections of BTX-A to hip adductors influence Reimers index helping to
      prevent norm value. After subsequent injections of BTX-A time period of
      therapeutic effect changes. Parents of treated children assess BTX-A therapy as
      highly effective.

PMID- 21853910
TI  - [Regulation of the differentiation of bone marrow mesenchymal stem cells into
      osteoblastic and adipogenic lineage].
AB  - The role of transcription factors and signalling pathways important for
      differentiation of bone marrow mesenchymal stem cell differentiation toward
      osteogenic and adipogenic lineage are briefly outlined.

PMID- 21853911
TI  - [Treatment of musculoskeletal injuries in children and adolescents during the
      Bone and Joint Decade 2000-2010].
AB  - Treatment of musculoskeletal injuries in children and adolescents during the Bone
      and Joint Decade 2000-2010 has changed substantially. This is connected both with
      the increasingly accurate and rapid diagnostics, as well as the emergence of
      specialized centers. The experiences gained from various centers to help choose
      the best and most effective method of supplying injuries. To review a set of
      patterns of conduct in individual locomotor injuries in children and adolescents,
      from the scene by emergency departments, to establish guidelines for specialist
      units. A more radical approach to the treatment of fractures can be justified in
      getting faster and better function, greater comfort without use of plaster casts
      and a short stay in hospital, which is extremely important for young patients.

PMID- 21853912
TI  - [Total hip replacement in psoriatic arthritis--raport of 4 cases].
AB  - BACKGROUND: It is unusual for the hips to be affected by psoriatic arthritis. But
      in that rare cases, totalhip replacement (THR) is at present an accepted
      treatment in patients with severe and painfull deformity. The aim of this paper
      is to evaluate the results of THR in patients suffering from psoriatic arthritis
      of the hip, operated from 2000 to 2008 in the Orthopaedic and Traumatologic
      Department of Poznan University of Medical Sciences. MATERIAL: Material included
      4 patients, 2 females and 2 males, on whom 5 THRs were performed, lateral
      approach was used in all cases. At the time of operation, the age of patients
      ranged from 48 to 61 years (mean 53). Follow-up ranged from 2 to 10 years (mean 6
      years). The operative treatment was a multistage process (during one operation
      only one joint was replaced). Cementeless total hip arthroplasty was used during
      all of the THRs. METHOD: The patients were clinically and radiologically
      evaluated preoperatively, postoperatively, and at final examination. The clinical
      state was evaluated with Harris hip score and WOMAC scale. We based our
      radiological examination on Hip Society system. RESULTS: The average preoperative
      Harris score for the group of patients was 31, WOMAC score 77. After an average
      of 6 years follow-up all hips were considered excellent, with average Harris
      score of 90, WOMAC Score of 5. All patients had increased function and decreased
      pain. The radiograms of all patients revealed that the acetabular and femoral
      components were correctly positioned with no radiographic evidence of loosening
      in the last examination. The inclination angle of the acetabular component was 30
      48 (mean: 39 degrees) and the acetabular opening angle was 3-20 degrees (mean: 4
      degrees). The stem was neutral-oriented in all hips. No ectopic ossification
      concentrations were found. CONCLUSION: The hip may be involved by the psoriatic
      arthritis. Clinical and radiological evaluation of our material showed that total
      hip replacement in the treatment of psoriatic arthritis allows regaining good
      lower limb function, which helps the patients staying less dependant on the
      surrounding environment. Ectopic ossification is not the clinical problem during
      THR in patients who suffer from psoriatic arthritis.

PMID- 21853913
TI  - [Replantation and revascularization of the thumb in musculoskeletal trauma center
      -presentation of 2 cases].
AB  - Summary We present two cases of successful microsurgical replantation and
      revascularization of the thumb of dominating extremity in young men performed in
      orthopedic department, to whom operative treatment in specialized replantation
      center could not be performed. Microvasculature of the finger was restored
      anastomosing microsurgically its artery and vein under operative microscope, and
      bone fracture was stabilized intramedullary with Kirschner wires. In both cases
      vitality of the finger was restored, which enabled proper healing of soft tissues
      and bone, leading to restoration of satisfactory function of the thumb. Due to
      high value for the function of the hand, thumb injuries threading with its loss
      should be managed primarily. Due to small vessel diameter those procedures
      require special instrumentation and trained personnel, and thus shouldbe done in
      replantation centers. Nevertheless, when treatment in an appropriate center is
      unavailable, those procedures could also be successfully performed by trained
      orthopedists.

PMID- 21853914
TI  - [Application of Ponseti method in case of neglected talipes equinovarus in 4
      years and 9 months old boy with DiGeorge syndrome--case report].
AB  - Case report of application of Ponseti method in treatment of neglected congenital
      talipes equinovarus in boy with DiGeorge syndrome who was 4 years and 9 months of
      age at the beginning of the treatment. Foot was classified as very severe, scored
      4.5 points according to Pirani and 15 points according to DiMeglio
      classification. After 9 casts set according to Ponseti protocol good correction
      of all components was achieved accept for the equinus deformity. Achilles
      lengthening procedure was done, but there was necessity to perform posterior
      release to achieve good dorsiflexion. Finally, goals of treatment were achieved:
      the foot is flexible, well shaped, pain free, ready for weight-bearing and use of
      commercial shoes. At current stage of treatment the foot scores 0.5 points
      according Pirani and 4 points according to DiMeglio classifications.

PMID- 21853915
TI  - [Cellular pathology and revolution of scientific medicine (on the occasion of the
      190th anniversary of Rudolf Virchow's Birth)].
AB  - Rudolf Virchow destroyed the old humoral pathology, created the doctrine of cell
      physiology and pathology, which has not lost its importance to date, described a
      great many pathological processes in detail, and put into practice appropriate
      terminology and classification. Up until the present pathology appreciably
      remains Virchow's cellular pathology despite modern science advances, inevitable
      changes and clarities of our ideas about the structure and function of organs and
      tissues. Virchow's cellular pathology has radically altered the view on the
      essence of painful processes, by opening a new epoch in the history of medicine
      and medical science.

PMID- 21853916
TI  - [The leading figure of Russian medicine (on the occasion of the 110th anniversary
      of A. I. Strukov's birth)].

PMID- 21853917
TI  - [Endometrial implantation window in infertility].
AB  - The paper presents the results of biopsy and curettage specimens from 92 patients
      with infertility. Histological and immunohistological (steroid receptors, Ki67,
      P27, and cyclin E) methods and scanning electron microscopy have been used. The
      substantial immunohistochemical (IHC) changes found in the endometrial
      implantation window in infertility are associated with the spectrum of the
      detected pathology. No clear correlations between the expression of IHC markers
      and the concentrations of serum hormones, which are characteristic of the normal
      menstrual cycle, may suggest that there is an imbalance of steroid reception at
      the endometrial tissue level. The detection of proteins P27 and cyclin E in the
      cytoplasm of glandular and stromal cells reflects the deficient block of a cell
      cycle essential for an adequate implantation window. The detected features of the
      superficial endometrial ultrastructure may be an additional indicator of the
      adequacy of endometrial secretory maturation. The essential histological,
      immunohistochemical, and ultrastructural features of the endometrium in
      infertility give valuable information that complements the traditional clinical
      classifications. Evaluation of the endometrial morphofunctional state opens up
      fresh opportunities to ensure an individual approach when using the regimens of
      assisted reproductive technologies.

PMID- 21853918
TI  - [Primary (idiopathic) cardiomyopathies].
AB  - The lecture gives the clinical and morphological characteristics of different
      forms of primary (idiopathic) cardiomyopathies. It presents macroscopic,
      histological, and ultrastructural changes in primary cardiomyopathies.

PMID- 21853919
TI  - [Pathologic anatomy of Barrett's esophagus].
AB  - It is most substantiated to define Barrett's esophagus as intestinal metaplasia
      of esophageal cardiac mucosa irrespective of its association with the
      endoscopically detected esophageogastric junction, which develops as a result of
      gastroesophageal reflux. There is a need for further investigations of the
      specific features of the cardiac-type mucosa. During endoscopic study, it is
      important to be alert when identifying short and ultrashort Barrett's esophagus
      and to sample sufficient biopsy material. A pathologist must differentiate three
      major types of the cylindrical epithelium of the esophagus: cardiac, acid
      producing cardiac, and intestinal metaplasia, by diagnosing Barrett's esophagus
      in the latter case. Patients with the esophageal cardiac mucosa should be
      referred to as a risk group for its development.

PMID- 21853920
TI  - [Morphogenesis of gastric mucosal atrophy as a basis of a phenotype of chronic
      gastritis].
AB  - Atrophic antral gastritis was found to show an absolute decrease in gland volume
      with higher expression of the gastric transcription factor Shh, i.e. absolute
      atrophy and that concurrent with the replacement of the specialized gastric
      epithelium by the intestinal MUC2-producing one, i.e. metaplastic atrophy. In
      atrophic multifocal gastritis along absolute and metaplastic atrophy, there are
      foci of the proliferative metaplastic epithelium, i.e. hyperproliferative
      metaplastic atrophy that is prevalent in atrophic pangastritis. The molecular
      characteristics of hyperproliferative metaplastic atrophy are varying: in some
      foci of metaplasia, the high proliferative activity of the epithelium is
      concomitant with the hyperexpression of P53, a marker of DNA damage, the lower
      expression of the intestinal transcription factor CDX-2, and the low level of
      Cpp32, an indicator of apoptosis. Whether such structures can be identified at
      the launching pad for tumor growth in atrophic pangastritis is discussed.

PMID- 21853921
TI  - [Parenchymal-stromal interactions in intestinal gastric cancer].
AB  - Histological, histochemical, and immunohistochemical investigations were
      performed in a prognostically favorable intestinal type of gastric carcinoma, by
      estimating mainly stromal and, to a lesser extent, parenchymal components, as
      well as their interactions at various stages of intraorgan tumor growth.

PMID- 21853922
TI  - [New feasibility of using a tissue culture technique in diagnostic oncomorphology
      in case of neuroblastoma and breast cancer].
AB  - The paper gives the results of investigating the cultured tissues from patients
      with breast cancer (BC) and those with neuroblastoma, by applying both the
      traditional studies and molecular genetic techniques (FISH). The cultures from
      the patients with neuroblastoma represented as three cell types--N, S, and I.
      There are certain similarities between the cell composition in the culture medium
      and the histological structure of the tumor. Mature neoplasms of the
      ganglioneuroma type contain S-type cells only while intermediate type I cells are
      a predominant element of immature neuroblastomas. The presence of a considerable
      number of I cells in the explants appears to suggest a poor prognosis even when
      the tumor has a comparatively mature structure as a whole. The results of FISH on
      explant cells presented a means of detecting a broad range of points that are not
      recorded on histologic specimens--amplification on the metaphase plate,
      localization of an amplified product, amplification on one chromosome, and double
      acentric chromosomes. The results of cultivation of BC cells are difficult to
      systematize although they offer the advantage of performing the FISH reaction.
      The authors recommend that the tissue culture method should be more extensively
      used in the day-to-day diagnostic work of pathology laboratories.

PMID- 21853923
TI  - [IgG4-related sclerosing disease].
AB  - IgG4-related sclerosing disease (IgG4-RSD) is a systemic one in which IgG4
      positive plasma cells and T lymphocytes extensively infiltrate various organs.
      The clinical manifestations of the disease include autoimmune pancreatitis,
      sclerosing cholangitis, cholecystitis, sialodenitis, retroperitoneal fibrosis,
      tubulointestitial nephritis, interstitial pneumonia, prostatitis, inflammatory
      pseudotumors and lymphadenopathy, all related with significantly elevated serum
      IgG4 levels. Tissue fibrosis with obliterative phlebitis of the affected organs
      is pathologically induced. The disease occurs predominantly in elderly men and
      responds well to steroid therapy. Since malignant tumors are frequently suspected
      on initial presentation, IgG4-RSD should be considered in the differential
      diagnosis to avoid unnecessary surgery.

PMID- 21853924
TI  - [Lymphoepithelial organs of the pharynx in children after local immunomodulatory
      therapy].
AB  - The immunomorphology of adenoids and hypertrophied palatine tonsils in frequently
      ill children after treatment with herbal and microbial immunomodulators reflects
      the functional tension and interaction of both innate and adaptive immunity
      cells. The increase in the count of BCL-2-expressing cells is considered as
      possible dysregulation of the physiological processes of positive and negative
      selection via apoptosis.

PMID- 21853925
TI  - [Correlations between placental morphological and functional parameters and
      neonatal status after normal full-term, prolonged pregnancy, and truly protracted
      pregnancy].
AB  - To solve the problem of differentiating protracted pregnancy, a special
      morphometric study was undertaken to examine three placental groups: 1) after
      normal full-term pregnancy (n = 35); 2) after prolonged pregnancy (n = 40); 3)
      after truly protracted pregnancy with partial or complete Clifford's syndrome (n
      = 30). A semiquantitative score (14 most important placental indicators),
      placenta and birth weights, Apgar scores, the infant's weight and height at the
      end of the first year of life were used so as to estimate the mild, moderate, and
      severe degree at 0.5, 1.5, and 3 points, respectively. One hundred and twenty-six
      possible pairs of structural and functional parameters were made up in all the
      groups. Pearson's correlation coefficient (r > 0.4) was applied to graphically
      display the pairs. Normal full-term pregnancy was characterized by few positive
      correlations mainly between the terminal villi and weight-height indices without
      associations with the Apgar scale. Prolonged pregnancy with the multiple
      placental tissue structural parameters along with organometric indices being
      involved was intermediate. The total scores permitted grades 1 and 2 chronic
      placental insufficiency (CPI) to be diagnosed in 27.5 and 2.5%, respectively. The
      severest form was truly protracted pregnancy that was distinguished by the
      maximum positive and negative correlations between all the parameters and the
      highest rate of diagnosis of CPI of grades 1 (45%) and 2 (15%). The findings
      strongly suggest that it is essential to identify prolonged and truly protracted
      pregnancy as important risk factors, by following up the infants for a year.

PMID- 21853926
TI  - [Fibrillary glomerulonephritis and immunotactoid nephropathy: the current view of
      the pathomorphological substrate of disease].
AB  - Fibrillary glomerulonephritis (FGN) and immunotactoid nephropathy (ITN) are
      diseases diagnosed only by electron microscopy. Until recently, information on
      the diseases has reached as reports on some cases. Much information, including
      the authors' observations, has been presently gathered so as there is a chance of
      attempting to pool and analyze it. It is quite obvious that investigators do not
      agree to evaluate FGN and ITN. Some authors are inclined to believe that these
      are one disease and propose to use the general term "fibrillary-immunotactoid
      nephropathy", we, like others, consider FGN and ITN as two different diseases.
      Our findings suggest that there are two diseases (FGN and ITN). We provide
      support for the data available in the literature on that the deposits are
      polyclonal in FGN and monoclonal in ITN. It is most likely that no sharp
      distinction can be made between FGN and ITN from the diameter of microtubules
      making up deposits (less or more than 30 nm); the procedure of their package and,
      to be sure, their chemical composition are of importance in establishing the
      diagnosis.

PMID- 21853927
TI  - [Primary amyloidosis with predominant involvement of the heart and
      gastrointestinal tract].
AB  - The paper describes a postmortem observation of primary cardiovascular AL
      amyloidosis first diagnosed by rectal biopsy in a 71-year-old woman. Death
      occurred due to chronic cardiovascular insufficiency 6 months after disease
      manifestation.

PMID- 21853929
TI  - Evaluation of IL-10 and TGF-beta levels and myeloid and lymphoid dendritic cells
      in ovarian cancer patients.
AB  - AIM: The aim of the study was to evaluate IL-10 and TGF-beta levels in the
      peritoneal fluid (PF) and plasma of patients with ovarian cancer (n=104), serous
      cyst (n=32) or normal controls (n=20). IL-10 and TGF-beta levels were correlated
      to myeloid (M) and lymphoid (L) dendritic cells (DC). MATERIAL AND METHODS: IL-
      10 and TGF-beta concentrations were evaluated using the enzyme linked
      immunosorbent assay (ELISA). The percentage of DC in mononuclear cells was
      quantified by using flow cytometry. RESULTS: The PF and plasma IL-10
      concentrations were significantly higher in epithelial ovarian cancer (EOC)
      patients when compared to the women with serous cyst (the reference group).
      Plasma levels of IL-10 were elevated in EOC patients in comparison with the
      reference and control groups. There were significant differences in the PF and
      plasma IL-10 levels with respect to tumor stage, grade and histology Significant
      negative correlations were found between the plasma IL-10 levels, MDC and LDC in
      the peripheral blood. TGF-beta levels were detected in PF of all EOC patients and
      were significantly lower when compared with plasma. Plasma levels of TGF-beta
      were elevated in EOC patients compared with the control group. No significant
      differences in the PF and plasma TGF-beta levels were noted between EOC patients
      and the reference group. The authors did not find a correlation between the
      plasma and PF TGF-beta levels and the percentage of MDC and LDC. CONCLUSIONS: IL
      10 production in EOC patients depends on the tumor stage, grade and histological
      type of the tumor cells. IL-10 may have impact on the percentage of dendritic
      cells in EOC patients.

PMID- 21853936
TI  - Epidemiological models for breast cancer risk estimation.
AB  - Breast cancer is the most common malignancy affecting women worldwide. Effective
      prevention and screening are only possible if there is precise risk prediction
      for cancer in an individual patient. Mathematical models for estimation of breast
      cancer risk were developed on the basis of epidemiological studies. It is
      possible to identify women at high risk for this disease using patient history
      data and the analysis of various demographic and hereditary factors. The Gail
      risk model, originally developed in the United States to selectively identify
      patients for breast cancer chemoprevention studies, remains to be the most widely
      used and properly validated. The Cuzick-Tyrer model is more advanced and was
      developed for the International Breast Intervention Study (IBIS-1). It
      incorporates the assessment of additional hereditary factors, body mass index,
      menopausal status and hormone replacement therapy use. Genetic models aiming at
      calculating individual risk for BRCA1 and BRCA2 mutation carrier-state have also
      been designed. In this review we discuss the usefulness of various risk
      estimation models and their possible application for breast cancer prophylaxis.

PMID- 21853935
TI  - [The role of 1691G>A (Leiden) mutation in Factor V gene, 20210G>A in prothrombin
      gene and 677C>T in MTHFR gene in etiology of early pregnancy loss].
AB  - OBJECTIVES: The objective of this study was to investigate the prevalence of
      common hereditary risk factors for thrombophilia (mutations 1691G>A, 20210G>A and
      677C>T variant in factor V Leiden (FV), prothrombin (FII) and MTHFR gene,
      respectively)--in a cohort of women with early pregnancy loss. MATERIAL AND
      METHODS: Frequency of mutations in FV, FII and MTHFR was assessed by PCR-RFLP or
      minisequencing in a cohort of 313 women with a history of at least two
      miscarriages and the control group consisting of 200 women without obstetric
      complications. RESULTS: Compared with controls, neither FV mutation (3.2% vs 3%;
      p=0.45) nor the MTHFR 677TT variant (8.4% vs 11.1%; p=0.58) was more prevalent in
      the patients. Mutation in FII gene was more frequent in the patients (3.5% vs
      0.5%; p=0.03) when compared with controls, however, the frequency of this
      mutation in controls was lower than estimated frequency in the population.

PMID- 21853931
TI  - Pro12Ala PPAR gamma2 gene polymorphism in women with polycystic ovary syndrome.
AB  - INTRODUCTION: The pathogenesis of PCOS has not been definitively determined and
      includes a number of genes linked with steroidogenesis, regulation of
      gonadotropin secretion, actions of insulin, obesity as well as chronic
      inflammatory processes. Some authors indicate that PPARgamma play a role in
      insulin sensitivity and are probably involved in hyperandrogenism in PCOS. The
      aim of the study was to assess the frequency of the Pro12Ala and Pro115Gln
      PPARgamma2 gene polymorphisms in women with PCOS. SUBJECTS AND METHODS: 54 PCOS
      women and 51 healthy women were recruited. Genetic studies to detect Pro12Ala and
      Pro115Gln PPARgamma2 gene polymorphism were performed. RESULTS: In the whole
      studied group the Pro115Gln polymorphism of the PPARgamma2 gene was not found.
      The frequency of the Pro12Ala polymorphism was estimated at 26.47% in the
      controls and at 23.15% in the PCOS patients. Women from the control and PCOS
      groups with BMI > or = 30 had statistically higher occurrence of the Ala allele
      than women with BMI <30 (38.80% versus 12.50% and 38.23% versus 18.75%).
      CONCLUSIONS: The frequency of the Pro12Ala polymorphism observed in the sample of
      women from the Lower Silesian population was significantly higher than in the
      majority of European populations.

PMID- 21853930
TI  - SDF-1alpha/CXCL12 and dendritic cells in ovarian cancer microenvironment.
AB  - AIM: To evaluate the a-chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12
      levels in the peritoneal fluid (PF) and plasma of patients with epithelial
      ovarian cancer (EOC, n=101), serous cyst (n=34) or normal controls (n=20). SDF
      1alpha concentrations were correlated to myeloid (M) and lymphoid (L) dendritic
      cells (DC). MATERIAL AND METHODS: SDF-1alpha levels were analysed using a
      sensitive enzyme-linked immunosorbent assay (ELISA). DC were evaluated by flow
      cytometry. RESULTS: The SDF-1alpha concentrations in peritoneal fluid were
      elevated in the EOC patients in comparison to the patients with serous cyst (the
      reference group). The PF SDF-1alpha levels were significantly higher in FIGO III
      and IV patients than in FIGO stage I. There were no significant differences in
      the PF SDF-1alpha levels with respect to tumor grade or histology Additionally
      there were no significant differences in the plasma SDF-1alpha levels in EOC
      patients in comparison with the reference and control groups. The SDF-1alpha
      levels in the plasma of FIGO stage III patients were significantly higher than
      that of stage I. Patients with undifferentiated carcinoma had significantly
      higher plasma SDF-1alpha levels than patients with serous cystadenocarcinoma. No
      significant differences were noted in the plasma SDF-1alpha levels within
      different tumor grades. There was no significant correlation between PF and
      plasma SDF-1alpha levels and the percentage of myeloid and lymphoid DC in the PB
      and PF of EOC patients. CONCLUSION: SDF-1alpha production in EOC patients may
      depend on the clinical stage of the tumor. Increased levels of SDF-1alpha and
      lymphoid DC in the PF of EOC patients may play an important role in the
      pathogenesis of this disease.

PMID- 21853933
TI  - [Radical trachelectomy--retrospective analysis of our own case material].
AB  - BACKGROUND: Cytologic prophylactic smears enable diagnosis of cervical cancer in
      early stages what may allow to preserve reproductive function in selected groups
      of patients. AIM: Retrospective analysis of our own material in term of oncologic
      treatment, obstetrics results and percent of surgical complications. MATERIAL AND
      METHODS: In our Department between 01. 06. 2003 and 01. 02. 2011, 14 patients
      were treated with laparoscopically assisted radical vaginal trachelectomy In all
      cases only sentinel node biopsy with negative results allowed to perform radical
      trachelectomy In one case tumor recurrence was diagnosed and the patient died.
      After the procedure two out of fourteen patients became pregnant. One of the
      patients delivered in 37th week of pregnancy and the other one miscarried in 11th
      week. Three patients suffered from surgical complications. CONCLUSIONS: Patients
      with tumor diameter < or = 2 cm can be treated by using laparoscopically assisted
      radical trachelectomy and oncologic results are comparable to classical surgery
      The number of surgical complications is slightly higher than in classical method
      but this method allows to preserve reproductive function in the treated women.

PMID- 21853934
TI  - [Differentiation of an integrated and episomal HPV-16 DNA using real-time PCR in
      cervical specimens of women diagnosed with intraepithelial lesions and invasive
      cervical cancer].
AB  - Persistent high-risk HPV infection, especially HPV-16, is considered to be an
      important step in the process of cervical carcinogenesis. Integration of viral
      DNA into the host genome through the destruction of HPV E2 sequences, increases
      the expression of viral proteins E6 and E7 and their participation in the
      transformation of cervical cancer. OBJECTIVE: The aim of this study was to apply
      real-time PCR (RT-PCR) to assess the prevalence of integrated and episomal HPV-16
      DNA and determine viral DNA load in women with cervical intraepithelial lesions
      and invasive cervical cancer MATERIAL AND METHODS: A total of 84 women infected
      with HPV-16, including 44 with LSIL, 7 with HSIL and 33 with invasive cervical
      cancer participated in the study Cervical specimens were collected using the
      cytobrush. The presence of a sequence of E2 and E6 HPV-16 and human gene RNasy P
      was detected by quantitative RT-PCR. The viral load presented as the form of the
      virus genome copy numbers per 1,000 cells. RESULTS: The integrated form of HPV-16
      genome was found in 97% of women with cervical cancer. In women with LSIL and
      HSIL mixed form (simultaneous occurrence of an integrated and episomal form) of
      the viral genome (84% and 57%, respectively) prevailed. The frequency of the
      integrated HPV-16 DNA increased with progression of dysplastic lesions of the
      cervix (p<0.001). Statistically significant differences in average number of
      copies of the virus in women with LSIL and HSIL compared to patients with cancer
      (p<0.001) were observed. The highest viral load was detected in women
      demonstrating an integrated HPV-16 DNA. CONCLUSIONS: Quantitative analysis of the
      sequence of E2 and E6 HPV-16 tested by RT-PCR can be used to determine the degree
      of integration of the viral genome and quantitative evaluation of viral load in
      clinical material. It can also serve as an additional parameter defining risk of
      progression of transformation in the cervix.

PMID- 21853937
TI  - [Water and its importance for female body].
AB  - Water is an essential part of every living organism. Homeostasis in the aspect of
      water is necessary to retain normal function of the body Even small dysfunction
      in its distribution may cause reversible and later irreversible changes in cell
      and organ functions. The quality and proper distribution of water is a necessary
      condition to maintain health at different stages of life. It is especially
      important in procreative period. The article presents the importance of water for
      the body and negative effects on health due to lack of water or its improper
      distribution, particularly with regard to pregnant and breastfeeding women.

PMID- 21853932
TI  - [The influence of low-dose oral contraceptive pill on clinical and metabolic
      parameters in young women with polycystic ovary syndrome].
AB  - Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism,
      oligo/anovulation and is associated with risk factors for cardiovascular
      diseases, such as insulin resistance and central adiposity. The aim of the study
      was to evaluation of influence of the oral contraceptive pill on the
      endocrinologic and metabolic parameters in women with PCOS. MATERIAL & METHODS:
      Forty nine PCOS women (aged 23,9 +/- 3,5 [mean +/- SD]) without any other
      diseases were included into the study. Oral contraceptives (0,02 mg
      ethynylestradiol + 0,15 mg desogestrel) were administered for 6 months. Hormonal
      and biochemical analyses were performed with specific assays at the beginning and
      after 6 month-therapy BMI, insulin sensitivity index (ISI) and QUICKI were
      calculated. Statistical analysis was performed using Wilcoxon test. RESULTS: All
      patients completed 6-month therapy and no severe side effects were reported
      during the study. A significant reduction in testosterone (T) concentrations was
      observed (p<0.005). We recorded a significant increase in lipid concentrations.
      CONCLUSIONS: The administration of oral contraceptives in our study group caused
      decrease in the testosterone level but negative effect on total cholesterol and
      triglycerides level was observed.

PMID- 21853928
TI  - [Morphological procedure for rectal cancer].
AB  - The morphological study of surgical specimens in rectal cancer involves
      assessment of the quality of mesorectumectomy, examination of serial sections of
      a tumor growth area, and study of the proximal, distal, and circulatory ends of
      resection as a criterion for the quality and efficacy of surgery. The circulatory
      end of resection is regarded as positive when it has tumor cells inside or within
      1 mm of it and the performed surgery is unradical. The data obtained with the use
      of this technology make it possible to most fully estimate the site and extent of
      a tumor process, to identify a number of important prognostic factors, and to
      assess the quality of a performed surgical intervention and preoperative
      diagnosis. The procedure is adapted to the standard technological equipment of
      morbid anatomy units.

PMID- 21853938
TI  - [Are in-utero interventions justified? - perspective of neonatologists. - Part
      II. Spina bifida, obstructive uropathy, pleural effusion].
AB  - INTRODUCTION: Spina bifida, obstructive uropathy and congenital pleural effusion
      (PE) belong to the group of congenital defects in which attempts of in-utero
      treatment were undertaken. OBJECTIVE: Main objective of our study was to search
      for scientific evidence that would justify offering, and performing, in utero
      interventions in fetuses with spina bifida, obstructive uropathy and PE. METHODS:
      Using Pubmed as the main source, all publications relevant to the subject of in
      utero interventions in fetuses with spina bifida, obstructive uropathy and PE
      were sought and carefully reviewed. An extra effort was made to identify all
      randomized controlled trials and meta-analyses. RESULTS: Up to date, none of the
      aforementioned in-utero interventions was evaluated in the randomized controlled
      trial. Two ongoing studies, one for patients with spina bifida, and one for
      patients with obstructive uropathy are still actively recruiting the subjects. As
      suggested by the results of meta-analysis, vesico-amniotic shunt might be
      recommended for selected group of fetuses with obstructive uropathy. For fetuses
      with unilateral or bilateral PE, in-utero drainage seems to improve the outcome
      only in cases complicated by hydrops fetalis. However only case series are
      available. CONCLUSIONS: Because of insufficient scientific evidence, offering in
      utero intervention to women with pregnancy complicated by spina bifida,
      obstructive uropathy and fetal PE on the routine basis is not justified. Until
      more data, preferably from randomized controlled trials are available, these
      procedures should only be performed in specialized centers as a part of carefully
      designed clinical trial.

PMID- 21853940
TI  - Placenta praevia increta with caesarean section scar invasion.
AB  - INTRODUCTION: Placenta increta refers to the placenta invading the myometrium. It
      is a rare but life-threatening condition. The incidence of placenta increta
      ranges widely from 1 in 540 to 1 in 93,000 deliveries; in Poland it is
      approximately 0.2% of all deliveries. The occurrence of placenta praevia increta
      is much lower and accounts for 0.001% to 0.05% of cases. However the frequency of
      this condition is steadily increasing. CASE REPORT: Placenta praevia was
      diagnosed in an ultrasound examination at 20 weeks' gestation in a multipara who
      had previously delivered by caesarean section. The invasion of the placental
      vessels into the caesarean section scar was observed in a Colour Doppler scan.
      The patient was admitted for a planned caesarean section at 36 weeks' gestation
      and invasion of the vessels into the caesarean scar was confirmed. Because of
      uncontrolled hemorrhage, a total abdominal hysterectomy was performed. The
      patient had an uneventful recovery and was discharged well on the fourth
      postoperative day with a healthy infant. CONCLUSIONS: Early antenatal detection
      of placenta praevia increta and planning the surgical intervention tailored to
      available resources and the patient's expectations result in reducing the number
      of postpartum maternal, as well as neonatal complications.

PMID- 21853939
TI  - Frasier syndrome in 17-year-old girl--case report.
AB  - The authors present a case of Frasier syndrome in a 17-year-old girl with
      nephrotic syndrome and male pseudohermaphroditism. Due to the existing risk of
      developing tumors in dysgenetic gonads, the patient was admitted to the clinic
      for prophylactic gonadectomy The operation was then postponed as a result of
      rapid progression to end-stage renal failure, and the patient was placed on
      hemodialysis. During subsequent laparoscopy both ovaries and dysgenetic gonads
      were resected. Histopathological examination revealed the presence of both
      seminal ducts and epididymis. Early prophylactic resection of dysgenetic gonads,
      such as was undertaken in this patient, is indicated in children with Frasier
      syndrome to prevent the development of germ cell tumors.

PMID- 21853945
TI  - The effect of genetic factors on the occurrence of myopia.
AB  - PURPOSE: The aim of this study was to investigate on a large population if and
      how genetic factors have an influence on the occurrence of myopia. MATERIAL AND
      METHODS: A total of 5533 students were examined (2659 boys and 2874 girls, in age
      6 18 years, mean age 11.9, S.D. 3.2). The examination included retinoscopy under
      cycloplegia induced with 1% tropicamide. Myopia was defined as a spherical
      equivalent of at least -0.5 dioptres. The students and their parents completed a
      questionnaire on the child's family history of myopia. Data analysis was
      performed using chi-squared test; p-values of < 0.05 were considered
      statistically significant. RESULTS: It was found that myopia occurs more often in
      students whose father (p < 0.001), mother (p < 0.001) or siblings (p < 0.0001)
      have myopia. A relation between the occurrence of myopia in grandparents and
      grandchildren was not observed (p > 0.05). CONCLUSIONS: The obtained results
      indicate that genetic factors have a significant effect on the occurrence of
      myopia.

PMID- 21853941
TI  - [Polish Gynecological Society standards of medical care in management of women
      with diabetes].

PMID- 21853943
TI  - The complications during phacoemulsification in patients with posterior polar
      cataract.
AB  - PURPOSE: The aim of the study was to evaluate the intraoperative complications
      during phacoemulsification of a posterior polar cataract, especially the risk of
      posterior capsule rupture. MATERIAL AND METHODS: The retrospective evaluation of
      complications during phacoemulsification of a posterior polar cataract in
      patients in the Department of Ophthalmology, Medical University of Warsaw from
      January 2001 to June 2007. The surgical procedures, as well as the implanted IOL
      type and intraoperative and postoperative complications were evaluated in every
      case in 2 years' observations. Best-corrected visual acuity before and 3 months
      after surgery was evaluated using the standard Snellen chart. RESULTS: The study
      group consisted of 16 individuals, 6 women and 10 men in age 21-55 (mean 32.7).
      22 eyes were operated on, all using the phacoemulsification method through
      corneal incision (10 individuals--1 eye, 6 individuals--both eyes). In all cases,
      phacoemulsification was performed using a hydrodissection free technique by
      corneal incision. A posterior capsule rupture was observed in 4 eyes (18%),
      localized in the central region and caused by changes in the capsula. The mean
      visual acuity was significantly better after cataract surgery. The best corrected
      visual acuity (BCVA) was 6/6 in 8 eyes (36%). A BCVA of less than 1.0 was caused
      by either amblyopia or nystagmus. CONCLUSIONS: Phacoemulsification in patients
      with posterior polar cataract is associated with a high risk of posterior capsule
      rupture and potential vitreous loss, which is why this procedure should be
      performed carefully by senior surgeons using an appropriate, hydrodissection free
      technique.

PMID- 21853944
TI  - [Posterior chamber intraocular lens implantation with one-point scleral fixation
      in children in long time observation].
AB  - MATERIAL AND METHODS: The study included 31 eyes in 31 children in age between 4
      and 12 years. One - point suture fixation of PC IOL to the sclera was performed
      primary, because of partial loss of the posterior capsule support. Poly-propylene
      suture 10-0 was used for IOL fixation. Rigid PMMA lenses and acrylic were sutured
      to the edge of incision. The ends of the propylene suture were buried between the
      2 edges of the sclera-corneal incision. Incision was closed with 8-0 nylon.
      Average time of observation was 8.4 years. RESULTS: Postoperative visual acuity
      was significantly improved after surgery in each case. Postoperative
      complications were minimal and not sight-threatening. CONCLUSIONS: This modified
      technique scleral-fixation of PC IOL implantation in some cases despite defective
      capsular support, can make up the effective method of surgical treatment without
      risk of IOL dislocation.

PMID- 21853948
TI  - [Peripheral retina in AMD patients].
AB  - PURPOSE: To determine the frequency and possible correlation between peripheral
      retinal lesions and AMD. MATERIAL AND METHODS: 92 patients (50-89 years old),
      with AMD were evaluated by indirect ophthalmoscopy and biomicroscopy with triple
      mirror. The control group consisted of 92 patients without any lesions in macula
      and other retinal changes. RESULTS: At the AMD patients the peripheral benign
      lesions were found more frequent than in control group (p = 0.003, especially:
      drusen (p = 0.026), atrophy (p = 0.011), and chorioretinal degeneration (p =
      0.001). CONCLUSIONS: The presence of peripheral retinal lesions may correlate
      with AMD evaluation.

PMID- 21853951
TI  - Comparison of the biometric measurements obtained using noncontact optical
      biometers LenStar LS 900 and IOL Master V.5.
AB  - PURPOSE: Evaluation of the measurement accuracy using a new optical biometer
      LenStar LS 900 (Haag Strait) and comparison according to the IOL Master V.5
      (Zeiss) device. METHODS: In a prospective clinical study biometric measurements
      along with artificial lens power calculation using the LenStar LS 900 device were
      performed. A total number of 106 patients qualified for a cataract extraction
      procedure were included in the study. Measurements along with lens power
      calculation were repeated using the IOL Master V.5. device. Results were
      elaborated using Pearson's correlation and Bland-Altman plot. RESULTS:
      Measurements were performed in 204 eyes of 106 patients. Mean values and ranges
      of biometry results were as follows: 23.46 +/- 2.81 mm [20.79-29.80] for IOL
      Master, and 23.47 +/- 2.83 mm [20.79-29.86] for LenStar LS 900. In keratometry
      for flat meridian (K1) the following data was obtained: mean 43.24 +/- 3.22 D
      [range 38.27-47.94] for IOL Master and 42.44 +/- 3.15 D [38.27-47.94] for LenStar
      LS 900. For steep meridian (K2) the data obtained were 44.14 +/- 3.40 D; [39.29
      49.13] and 43.27 +/- 3.34 D [38.61-48.4] respectively. The obtained calculation
      results for each eye were as follows: mean 21.23 +/- 8.07, [range 3.25-28.99] for
      Hagis formula, 21.14 +/- 6.90; [4.83-27.6] for SRK II, 21.04 +/- 7.78; [3.05
      28.05] for SRK/T, 21.09 +/- 8.13; [2.43-28.61] for Holladay using IOL Master and
      21.41 +/- 8.23; [2.99-29.15] for Haigis; 21.24 +/- 7.00; [4.6-27.71] for SRK II,
      21.13 +/- 7.90; [2.76-28.18] for SRK/T; 21.09 +/- 8.13; [2.16-28.76] for Holladay
      using LenStar LS 900. CONCLUSIONS: The LenStar LS 900 device enables to perform
      accurate and repetitive biometric measurements and implant power calculations.
      Implant calculation results obtained using the LenStar LS 900 device are
      comparable to those achieved using the IOL Master V.5 device, which has been
      commonly accepted as standard for over a decade. The use of both devices is
      limited by significant lens opacification and posterior capsule calcification. In
      such cases, additional ultrasound biometry should be performed. Keratometry
      results obtained using both devices should not be used alternatively because of
      the different measurement methods and different refraction indexes. The LenStar
      LS 900 device comparing to the IOL Master additionally enables pachymetry,
      macular retinal thickness, lens thickens and pupil diameter measurement. Accuracy
      of those measurements should be studied in the future.

PMID- 21853947
TI  - [Serum antiretinal antibodies (ARA) in patients with exudative age-related
      macular degeneration (AMD) treated with transpupillary thermotherapy (TTT) alone
      and with transpupillary thermotherapy (TTT) combined with injection of
      triamcinolone acetonide (sTTA) under posterior Tenon's capsule].
AB  - PURPOSE: To assess serum level changes of antiretinal antibodies (ARA) in
      patients with exudative age-related macular degeneration (AMD), treated with
      transpupillary thermotherapy (TTT) alone and with TTT combined with injection of
      triamcinolone acetonide (sTTA) under posterior Tenon's capsule and to compare the
      efficacy of TTT and TTT+sTTA. The purpose of the study was also to estimate if
      serum ARA may act as the biomarker of AMD. MATERIAL AND METHODS: This prospective
      study comprised 46 patients (46 eyes) with exudative AMD. Patients were assigned
      into: group I (n = 24) received TTT alone and group II (n = 20) received TTT with
      sTTA. Follow-up was at 3, 6, 9 and 12 months, when best-corrected visual acuity
      (BCVA), Amsler grid-test, intraocular pressure (IOP), fluorescein angiography
      (FA) and central retinal thickness (CRT) by optical coherence tomography (OCT)
      were assessed. In all patients serum ARA was determined using indirect
      immunofluorescence (IIF) method on normal monkey retina as antigens substrate and
      FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody.
      RESULTS: Baseline serum ARA titres in group I ranged from 1: 40 to 1: 5120 and in
      group II--1: 40 to 1: 1280 (p = 0.1). In control group serum ARA was present in
      46.4% of sera in titres from 1: 10 to 1: 40. These differences were statistcally
      significant (p < 0.001). Nine fluorescence patterns of ARA were detected by IIF
      method in both groups of AMD patients, while control sera showed only three types
      of reaction. Statistically significant correlation was found between CNV size,
      CRT and serum ARA titres in both groups of patients (p < 0.01). In a follow-up
      period decreasing serum ARA titres were noted, specially for subjects treated
      with combined therapy, however it was not statistically significant at 3, 6 and 9
      months while achieved significance (p < 0.01) at month 12. BCVA improvement or
      stabilization was observed in 64% of eyes in group I and in 75%--in group II (p =
      0.1). No leakage on FA was found in 66.7% and 70% of cases, in group I and II,
      respectively (p = 0.01). CRT reduction was observed in 50% (group I) and in 70%
      (group II) of eyes (p = 0.01) at month 12. CONCLUSIONS: Our preliminary
      observations indicate that serum ARA changes may reflect the activity of CNV in a
      course of AMD and may act as the biomarker of treatment efficacy. The use of sTTA
      in conjunction with TTT for CNV in AMD showed a tendency towards lower serum ARA
      titres and better functional results after treatment as compared with eyes
      treated with TTT alone.

PMID- 21853950
TI  - [Influence of the lutein-rich products consumption on its supply in diet of
      individuals with age-related macular degeneration (AMD)].
AB  - PURPOSE: The aim of the study was analysis of the influence of the lutein-rich
      products consumption on its supply in diet of individuals with age-related
      macular degeneration MATERIALS AND METHODS: The object of conducted analysis were
      127 nutrition questionnaires from 64 individuals with AMD (44 female, 20 male)
      and 63 without AMD--control group (49 female, 14 male). The age of participants
      was 50-88. The nutrition questionnaire concerned: AMD and its course, consumption
      of lutein-rich products and lutein supplementation. Lutein supply was assessed on
      the base of most often consumed products and lutein content in typical servings
      as well as on the base of applied supplementation. RESULTS: Patients with AMD, in
      comparison with control group, were significantly more often choosing green bean,
      parsley, dill (Anethum graveolens) and young beetroot leaves, as well as were
      consuming more diversified lutein-rich products. Lutein supply from diet was
      significanly increased in case of spinach consumption (very high in lutein) and
      broccoli consumption (high in lutein and chosen relatively often). Other products
      did not cause increase of lutein supply from diet, even if they evoked increase
      of lutein content in the typical serving or of quantity of servings. CONCLUSIONS:
      Patients with AMD, in comparison with healthy individuals, more often consume
      lutein-rich products, but lutein supply from diet in both groups do not differ.
      Significant increase of lutein supply may be achieved only by consumption of
      products characterized by the highest content of it. Patients with AMD, in
      comparison with healthy individuals, more often apply lutein supplementation,
      that influences lutein daily supply.

PMID- 21853952
TI  - The use of dynamic magnetic resonance in the diagnosis of ocular motility
      disorders.
AB  - Dynamic Magnetic Resonance (dMRI) of the extraocular muscles is based on
      performing a number of short sequences, while the patient fixates consecutive
      points placed in different positions of gaze. PURPOSE: To check the relation
      between dMRI findings and the results of clinical examination in patients with
      various types of strabismus. MATERIALS AND METHODS: We have selected three
      patients with lateral rectus palsy, superior rectus palsy and inferior rectus
      restriction from the group, in which we have performed dMRI. We have taken
      measures of the affected muscles shape, sectional area and volume. The results
      were related with the clinical examination. RESULTS: The measurements obtained
      with use of dMRI reflect the actual state of the affected muscle as seen on the
      Hess screen. The limitation of the muscles action is represented by a lack of
      increase in the sectional area and volume in respective gaze intervals. The
      restriction of the muscle affects its shape by pulling it towards the place of
      entrapment. CONCLUSIONS: Data acquired by means of dMRI correspond to the
      clinical findings and allow a quantitative analysis of the degree of muscle
      weakness. Defining the extent of the morphological changes in extraocular
      muscles, related with long-lasting paralysis, let us make an informed decision
      regarding further treatment.

PMID- 21853953
TI  - [Combined pharmacological-surgical treatment in exudative age-related macular
      degeneration].
AB  - PURPOSE: The aim of this paper is to present the early phase of treating
      exudative age-releted macular degeneration (AMD)--coexisting witch vitreoretinal
      pathology--with combined pharmacological-surgical therapy. MATERIAL AND METHODS:
      Our observation is based on one clinical case of combined therapy: pars
      planavitrectomy (PPV) and one intravitrealranibizumab injection. Observation is
      being carried on larger patient group according to the treatment scheme presented
      In this paper. RESULTS: In this case described combined pharmacological-surgical
      therapy allowed a significant improvement in visual acuity and closure of
      choroidal neovascularization (CNV), leakage confirmed by fluorescein angiography
      (FA) and optical coherence tomography (AMD). The treatment is being continued-
      another ranibizumab injection according to PRONTO study reinjection criteria.
      CONCLUSIONS: The pathomechanism of exudative AMD and coexistance of vitreoretinal
      pathology implications confirm reasonability of combined therapy.Due to actual
      clinical studies: the pharmacological -surgical treatment reduces the number of
      required intravitreal anti-VEGF agents injections. To confirm this observation we
      need to perform large randomised clinical studies.

PMID- 21853954
TI  - [Intravitreal Bevacizumab injections in a child with choroidal neovascularization
      -case report].
AB  - A healthy 11 year old boy with active choroidal neovascularization (CNV) was
      referred to the Department of Ophthalmology in Wroclaw for unilateral visual
      deterioration from 2 weeks. The best-corrected visual acuity was counting fingers
      from 4 meters. Boy was successfully treated with three intravitreal injections of
      bevacizumab. Intravitreal bevacizumab was well tolerated, choroidal
      neovascularization involuted, and best-corrected visual acuity improved to 20/32.
      The boy remained stable for 6 months after injections.

PMID- 21853955
TI  - Patomechanisms in proliferative vitreoretinopathy.
AB  - Proliferative vitreoretinopathy (PVR) remains the most common cause of recurrent
      retinal detachment following retinal detachment surgery. The development of PVR
      is a complex process involving humoral and cellular factors. Surgical treatment
      of PVR, which consists of removal of the fibrous membranes and restoration of
      physiological anatomic ocular conditions is often unsuccessful. Therefore the
      surgery should by backed up by local medication to inhibit new formation of
      proliferative lesions. Unfortunately, there is no satisfactory antiproliferative
      treatment available so far. Proliferative vitreoretinopathy remains a therapeutic
      challenge.

PMID- 21853946
TI  - [Uveitis in patients with multiple sclerosis].
AB  - Multiple sclerosis (SM) is an idiopathic, demyelinating CNS disease, with often
      ocular manifestations. Besides the most common SM ocular manifestation-optic
      neuritis, particular attention should be paid to uveitis. It is estimated that
      uveitis is ten times more frequent in population with SM than on population
      without it. PURPOSE: The aim of this study is to present our own observation of
      clinical course of the uveitis in SM patients. MATERIAL AND METHODS: We studied 9
      patients (7 women and 2 men), who had been treated in 2nd Department of
      Ophthalmology Lublin Medical School in 1993-2006. In I group (2 persons) uveitis
      was casually diagnosed during an ophthalmic examination in patients with SM. In
      II group (2 persons), first event of the uveitis was observed in patients with
      already diagnosed SM. In III group (2 persons), initial diagnose was uveitis, and
      subsequently SM was diagnosed. Group IV consisted of patients with uveitis, who
      developed SM several years later (3 persons). RESULTS: Clinical course of
      inflammatory process was bilateral, severe and chronic with exacerbation.
      Panuveitis, cystoid macular oedema, cataract formation, and glaucoma were the
      most often findings. All of patients were treated with corticosteroids. Therapy
      with corticosteroids caused improvement in all patients. CONCLUSIONS: The
      possibility of co-existence of SM and uveitis should be emphasized.
      Corticosteroids are efficient in the treatment of ocular complications in
      patients with SM.

PMID- 21853942
TI  - A retrospective analysis of the intraocular lens power calculation in cases of
      sulcus fixation.
AB  - PURPOSE: To evaluate the refractive results in patients with intraocular lenses
      fixated in the sulcus of posterior chamber. Sulcus fixation causes a more
      anterior position of IOL than had been intended during the preoperative power
      calculation. A lack of correction of the IOL's power results in a myopic shift.
      MATERIAL AND METHODS: 27 patients (27 eyes) who underwent cataract surgery by
      phacoemulsification and foldable IOL MA60BM sulcus fixation due to a posterior
      capsule rupture at the Department of Ophthalmology, Medical University of Warsaw.
      The position of the IOL was confirmed by ultrabiomicroscopy. The study included
      patients with axial lengths ranging from 22 to 25 mm. Patients who suffered from
      a corneal astigmatism of > 1,00 Dcyl prior to the surgery were excluded from the
      study. The study also excluded patients with vitreous loss as this causes the
      anterior chamber to become deeper after vitrectomy, and consequently the IOL
      might sit in a more posterior position. The difference between the predicted and
      the postoperative refraction was evaluated. RESULTS: The mean visual acuity was
      significantly better after cataract surgery. The best corrected visual acuity
      (BCVA) was 1.0, which occurred in 19 cases (70%). The myopic shift, which was
      assessed as a mean difference between the predicted and the postoperative
      refraction after sulcus fixation, was 1.25 D. CONCLUSIONS: In order to avoid a
      myopic shift in the case of sulcus fixation, the IOL power calculation should be
      adjusted accordingly. The authors recommend that the IOL power should be reduced
      by approximately 1.25 to 1.50 D in emetropic eyes.

PMID- 21853949
TI  - [Azithromycin in prophylaxis of intravitreal injections in patients with wet age
      related macular degeneration].
AB  - Endophthalmitis is one of the most dangerous complications after intravitreous
      drug injection. Preparing a patient to the injection general and topical
      endophtalmitis development risk factors should be eliminated. Antibiotic
      injection prophylaxis is still an important issue. PURPOSE: This research has to
      evaluate effectiveness and tolerance of Azithromycin (Azyter, Thea), in injection
      as an antibiotic prophylaxis in patients suffering from age-related macular
      degeneration (AMD). MATERIAL AND METHODS: The study was conducted in Ophtalmology
      Department (Medical Military Institute, Warsaw, Poland), in the group of 52
      patients, who underwent 52 intraocular injections of anti-VEGF because of AMD.
      Topical Azithromycin had been administrated twice a day to both eyes in 2 days
      before injection. On the third day injection was performed in aseptic conditions.
      One drop of Azithromycin had been administrated to each eye directly before
      injection and one drop after the procedure. At that moment antibiotic prophylaxis
      was terminated. RESULTS: Topical tolerance and effectiveness were evaluated. In 2
      cases (3.8%) intensive allergic reaction was reported (significant conjuctives
      oedema, itch, bloodshot), what caused change of antibiotic. In 5 cases (9%) light
      bloodshot was reported. 12 patients (23%) reported light or moderate foreign body
      sensation and in 2 cases (3.8%) the sensation was significant. No reaction of
      ophthalmic inflammation was reported 5 days after injection, moreover foreign
      body sensation and bloodshot were absent. 30 patients (57%) were satisfied with
      new and simplier scheme of antibiotic injection prophylaxis (twice a day for 3
      days). CONCLUSIONS: Azithromycin is a comfortable alternative for other topical
      antibiotics, especially in repetitive procedures like anti-VEGF injections. High
      Azithromycin concentration in tissues, tear film, and on the ophthalmic surface,
      protects injection site and inhibits growth of primary and mutual bacterial
      colonies. Short-term exposition to Azithromycin decrases risk of drug resistance
      development.

PMID- 21853956
TI  - [Glaucoma in the myopic patient--diagnostic problems].
AB  - Myopic eyes represent a special problem in the diagnosis of glaucoma. First,
      glaucomatous changes of the optic disc can be masked by the usual myopic conus,
      tilting of the disc and circumpapillary atrophy. Second, the ocular rigidity is
      usually lower than in normal eyes, therefore intraocular pressure must be checked
      with applanation or contour tonometry. Third, glaucomatous changes in the visual
      field of myopic patient may be thought to be caused by the myopic conus,
      staphyloma or choroidal atrophy. The discerning clinician must be doubly on guard
      for glaucoma in myopic patients. This is especially important because glaucoma
      occurs more frequently in myopic patients.

PMID- 21853957
TI  - [Optical coherence tomography in the imaging of the iridocorneal angle].
AB  - Anterior segment optical coherence tomography (AS OCT), enables visualization and
      measurements of the anterior segment of the eye. In particular, it is a valuable
      tool in the imaging of the iridocorneal angle. In this paper, we reviewed
      parameters used for analysis of the iridocorneal angle in AS OCT and compared
      changes of these parameters after cataract surgery, laser iridotomy and
      illumination. Special attention was paid to changes of such quantitative
      parameters as TISA (trabecular-iris space area), AOD (angle opening distance),
      and ARA (angle recess area).

PMID- 21853959
TI  - The first signs of glaucomatous cupping in the optic nerve.
AB  - Evaluation of the optic disc is important for both the diagnosis of glaucoma, and
      in monitoring the progress of glaucoma. Along with visual field examination, it
      allows the presence of glaucoma to be recognized, and for progressive damage to
      be seen. Glaucoma can occur despite intraocular pressure (IOP) in the normal
      range, but as importantly, can be absent even when the IOP is distinctly high.

PMID- 21853958
TI  - [IThe use of Pentacam for keratoconus diagnosis and progress evaluation].
AB  - The authors present possibilities of Pentacam examination for keratoconus
      diagnosis and progress evalutaion. They describe meaning of data comming from
      Pentacam 3D model measurements; indexes for corneal surface disturbances,
      analysis of anterior and posterior corneal surface, sense of connection data from
      keratometric and pachymetric measurements for keratoconus detection.

PMID- 21853962
TI  - Femtosecond LASIK retreatment using side cutting only.
AB  - PURPOSE: To present visual and refractive outcomes in 11 eyes that underwent
      femtosecond LASIK and subsequent retreatment with flap lifting using only side
      cutting. METHODS: Seven patients (11 eyes) with a mean age of 30.55+/-5.42 years
      (range: 24 to 39 years) underwent retreatment 18.18+/-5.41 months (range: 12 to
      26 months) after primary LASIK treatment with side cutting only using a
      femtosecond laser for the correction of residual refractive error. RESULTS: Mean
      follow-up after retreatment was 7.72+/-1.48 months (range: 6 to 10 months). No
      intra- or postoperative complications were found after LASIK retreatment.
      Uncorrected distance visual acuity (UDVA) improved in all patients. Mean UDVA
      improved from 0.54+/-0.12 (decimal scale) (range: 0.4 to 0.7) preoperatively to
      0.99+/-0.03 (range: 0.9 to 1.0) after retreatment. No patient lost lines of
      corrected distance visual acuity. CONCLUSIONS: Retreatment using a femtosecond
      laser to create only a side cut is an effective modality to treat residual
      refractive errors in postoperative LASIK patients.

PMID- 21853961
TI  - Bilateral ring-shaped intrastromal opacities after corneal cross-linking for
      keratoconus.
AB  - PURPOSE: To report a case of bilateral, ring-shaped, intrastromal corneal
      opacities after corneal cross-linking (CXL) for progressive keratoconus. METHODS:
      A 21-year-old man with bilateral, progressive keratoconus underwent CXL with
      riboflavin 0.1% and ultraviolet A (UVA) light in the right eye and, 6 months
      later, in the left eye. RESULTS: One day after CXL, the right eye showed a
      sharply demarcated white ring in the corneal periphery. The ring involved the
      superficial stroma at 2 mm from the limbus, extended from 1 to 11 o'clock, and
      was 1.5-mm wide. Corneal topography showed marked central flattening. Six months
      after treatment, a residual, faint, ring-shaped opacity remained, with a decrease
      in corneal ectasia. Cross-linking was then performed in the left eye. Different
      ultraviolet devices were used in the two eyes. On postoperative day 1, the left
      eye also showed a white ring of stromal opacity. Scheimpflug imaging showed
      corneal stromal contraction in the zone of whitening. At final examination, >1
      year after surgery, corrected visual acuity was 0.00 logMAR with cylinder of 2.00
      diopters in both eyes. CONCLUSIONS: The bilateral intrastromal corneal changes
      were innocuous in the long-term, with preservation of good visual acuity and
      successful stabilization of progressive keratoconus.

PMID- 21853960
TI  - Analysis of microkeratome thin flap architecture using Fourier-domain optical
      coherence tomography.
AB  - PURPOSE: To assess the corneal architecture and reproducibility of LASIK flap
      thickness created by the Amadeus II mechanical microkeratome (Ziemer Ophthalmic
      Systems AG) using Fourier-domain optical coherence tomography (OCT; Optovue Inc).
      METHODS: Anterior segment Fourier-domain OCT was used to analyze the morphology
      of 58 LASIK flaps from 30 patients created with the Amadeus II microkeratome 140
      MUm head and ML7090CLB blades (Med-Logics Inc) at 2 weeks postoperatively. Flap
      thickness was assessed at 10 points across the central 6 mm of the cornea
      (horizontal and vertical meridians). Postoperative central corneal flap thickness
      measured by Fourier-domain OCT was compared with intraoperative ultrasound
      pachymetry measurements. RESULTS: No significant difference was noted between
      central flap thickness measured by intraoperative pachymetry (107.2 +/- 14 MUm)
      and postoperative OCT (111.7 +/- 11 MUm; P=.07, correlation coefficient=0.86).
      Fourier-domain OCT measurements demonstrated functionally planar flap
      architecture (standard deviation [SD] of thickness across the flap=4.9 MUm, SD
      range across the flap=2 to 9 MUm) for the microkeratome flaps. CONCLUSIONS: The
      Amadeus II microkeratome with Med-Logics blades created thin, reproducible,
      functionally planar flaps as measured by Fourier-domain OCT. Central flap
      thickness measured by intraoperative ultrasound pachymetry was equivalent to that
      measured 2 weeks postoperatively by OCT.

PMID- 21853964
TI  - Microwave-assisted construction of ferromagnetic coordination polymers of
      [W(V)(CN)8]3- with Cu(II)-pyrazole synthons.
AB  - The microwave-mediated self-assembly of [W(V)(CN)(8)](3-) with Cu(II) in the
      presence of pyrazole ligand resulted in the formation of three novel assemblies:
      Cu(II)(2)(Hpyr)(5)(H(2)O)[W(V)(CN)(8)](NO(3)).H(2)O (1),
      {Cu(II)(5)(Hpyr)(18)[W(V)(CN)(8)](4)}.[Cu(II)(Hpyr)(4)(H(2)O)(2)].9H(2)O (2), and
      Cu(II)(4)(Hpyr)(10)(H(2)O)[W(V)(CN)(8)](2)(HCOO)(2).4.5H(2)O (3) (Hpyr =1H
      pyrazole). Single-crystal X-ray structure of 1 consists of cyanido-bridged 1-D
      chains of vertex-sharing squares topology. The structure of 2 reveals 2-D hybrid
      inorganic layer topology with large coordination spaces occupied by
      {Cu(Hpyr)(2)(H(2)O)(4)}(2+) ions. Compound 3 contains two types of cyanido
      bridged 1-D chains of vertex-sharing squares linked together by formate ions in
      two directions forming hybrid inorganic-organic 3-D framework (I(1)O(2)). The
      magnetic measurements for 1-3 reveal a weak ferromagnetic coupling through Cu(II)
      NC-W(V) bridges.

PMID- 21853967
TI  - Palladium-catalyzed alkylation of ortho-C(sp2)-H bonds of benzylamide substrates
      with alkyl halides.
AB  - A highly efficient and generally applicable method has been developed to
      functionalize the ortho-C(sp(2))-H bonds of picolinamide (PA)-protected
      benzylamine substrates with a broad range of beta-H-containing alkyl halides.
      Sodium triflate has been identified as a critical promoter for this reaction
      system. The PA group can be easily installed and removed under mild conditions.
      This method provides a new strategy to prepare highly functionalized benzylamines
      for the synthesis of complex molecules.

PMID- 21853966
TI  - Antioxidant potential of glutathione: a theoretical study.
AB  - All possible X-H (where X can be C, N, O or S) bond dissociation energies (BDEs)
      of glutathione (gamma-L-glutamyl-L-cysteinyl-glycine, GSH) and its fragments have
      been calculated by first principle methods, and the antioxidant potential of GSH
      was revealed to be higher than expected in earlier studies. Electron
      delocalization was found to have an important influence on the antioxidant
      potential. All structures were optimized and their harmonic vibrational
      frequencies were calculated in the gas phase at the B3LYP/6-31G(d) level of
      theory. Solvent effects were taken into account for optimizations at the same
      level of theory by applying the conductor-like polarizable continuum model
      (CPCM). Hydrogen cleavage from glutathione proved that the G3MP2B3 composite
      method provides results consistent with the experimental values for bond
      dissociation enthalpies (DH(298)) of S-H, O-H, C-H, and N-H bonds. In order to
      replace the G3MP2B3 energies with accurate single point calculations, six density
      functionals, namely, MPWKCIS, MPWKCIS1K, M06, TPSS1KCIS, TPSSh, and B3LYP, were
      tested against G3MP2B3 for obtaining accurate bond dissociation energies. The
      MPWKCIS1K/6-311++G(3df,2p)//B3LYP/6-31G(d) level of theory provides the best
      correlation with the G3MP2B3 method for BDEs in both phases, and therefore, it is
      recommended for similar calculations. Gas phase results showed that the O-H bond
      was the weakest, while in aqueous phase the N-H bond in the ammonium group proved
      to have the smallest BDE value in the studied system. In both cases, the cleavage
      of the X-H bond was followed by decarboxylation which was responsible for the
      energetic preference of these processes over the S-H dissociation, which was
      regarded as the most favorable one until now. The calculated BDE values showed
      that in aqueous phase the most preferred H-abstraction site is at the weakest N-H
      bond (BDE(aq) = 349.3 kJ mol(-1)) in the glutamine fragment near the alpha
      carbon. In water, the formation of N-centered radicals compared to S-centered
      ones (BDE(aq) = 351.7 kJ mol(-1)) is more endothermic by 2.54 kJ mol(-1), due to
      decarboxylation. Hydrogen dissociation energies from the alpha-carbons are also
      comparable in energy with those of the thiol hydrogen, within computational
      error. The higher stability of the radicals--except the S-centered ones--is due
      to various degrees of electron delocalization. In aqueous phase, four quasi
      equivalent stable radical centers (the alpha-carbons, the N-centered radical of
      the NH(2) group, and the S-centered radical) were found which provide the
      antioxidant behavior of glutathione.

PMID- 21853965
TI  - Hexanuclear dysprosium(III) compound incorporating vertex- and edge-sharing Dy3
      triangles exhibiting single-molecule-magnet behavior.
AB  - A unique hexanuclear dysprosium(III) compound with a new polydentate Schiff-base
      ligand shows complex slow relaxation of the magnetization most likely associated
      with the single-ion behavior of individual Dy(III) ions as well as the possible
      weak coupling between them.

PMID- 21853963
TI  - Comparison of optical aberrations and contrast sensitivity between aspheric and
      spherical intraocular lenses.
AB  - PURPOSE: To compare visual acuity, aberrometry, and contrast sensitivity in
      patients who had a spherical intraocular lens (IOL) (SoFlex SE, Bausch & Lomb)
      implanted in one eye and an aspheric IOL (SofPort AO, Bausch & Lomb) implanted in
      the fellow eye during uncomplicated cataract surgery. METHODS: A prospective,
      multicenter, double-blind study was performed. Forty patients (80 eyes) underwent
      bilateral phacoemulsification with implantation of a spherical IOL in one eye and
      an aspheric IOL in the fellow eye. Postoperatively, visual acuity, aberrometry,
      and contrast sensitivity tests were performed. Statistical analyses were
      performed using Student t and Wilcoxon tests, and mixed effects were used for
      each contrast condition situation. RESULTS: Thirty-nine patients (30 women, 9
      men; 78 eyes) with a mean age of 69.3+/-6.17 years (range: 51 to 82 years)
      completed the study. No statistical differences were found regarding visual
      acuity among eyes. Lower levels of higher order aberrations were achieved in the
      aspheric group. No statistical difference between groups under photopic
      conditions was noted. In low spatial frequencies, better performance was observed
      with the aspheric IOL under mesopic conditions. In high spatial frequencies, the
      spherical IOL produced better quality of vision. Comparing mesopic conditions
      with glare, visual performance was statistically better using the aspheric IOL.
      CONCLUSIONS: Cataract surgery results cannot be measured by means of visual
      acuity alone. Quality of vision must be considered, and implantation of IOLs with
      low levels of spherical aberrations and better contrast sensitivity are
      preferred. In this study, the aspheric IOL demonstrated better visual function,
      especially at night, when compared with spherical IOLs.

PMID- 21853969
TI  - Methyl formate and its mono and difluoro derivatives: conformational manifolds,
      basicity, and interaction with HF theoretical investigation.
AB  - The conformational manifolds, scenarios of protonation, and hydrogen bond
      propensity of methyl formate and its mono and difluoro derivatives, which possess
      two oxygen atoms with different basicities, are studied at the B3LYP/6
      311++G(3df,3pd) computational level. The optimized geometries of the title
      molecules, their energetics, and relevant harmonic vibrational frequencies,
      mainly of the nu(CH) mode of the H-C?O group, are of a primary focus. The Natural
      Bond Orbital analysis is invoked to obtain the second-order intra- or
      intermolecular hyperconjugation energies, occupations of antibonding orbitals,
      and hybridization of the carbon atoms. It is demonstrated that the Z conformers
      (and their rotamers) of the three title molecules are characterized by a higher
      stability compared to the E ones. The stabilities depend on the intramolecular
      hyperconjugative interaction and on the attraction or repulsion nonbonded
      interaction. The proton affinity of the carbonyl oxygen exceeds, by 15-20
      kcal.mol(-1), that of the methoxy oxygen. Fluorine substitution causes a moderate
      lowering of the proton affinity of the oxygens. Protonation on the oxygen atoms
      yields a contraction of the C-H bond and large concomitant blue shift of the
      nu(CH) vibration. These changes are mainly determined by a lowering of the
      occupation of the corresponding sigma*(CH) orbitals. The esters under
      consideration are probed on the interaction with the HF molecule. The complexes
      that are formed under this interaction on the oxygen of the H-C?O group are
      stronger than those formed on the oxygen belonging to the methoxy one. It is
      deduced that the hydrogen bond energies show a linear dependence on the proton
      affinities of the corresponding oxygen atoms. Hydrogen-bonded complexes of
      moderate strength are also formed, while HF interacts with the fluorine atoms of
      the fluorinated esters.

PMID- 21853972
TI  - Photochromic and redox properties of bisterpyridine ruthenium complexes based on
      dimethyldihydropyrene units as bridging ligands.
AB  - We report herein the synthesis and characterization of four new bisterpyridine
      dinuclear ruthenium complexes containing the dimethyldihydropyrene (DHP)
      photochrome as bridging ligand. A synthetic strategy has been developed based on
      a Suzuki coupling reaction to synthesize these novel terpyridine-DHPs. The
      reactivity of these different ligands and dinuclear ruthenium complexes with
      light was examined by (1)H NMR and monitoring the changes in their absorption
      spectra upon irradiation at controlled wavelengths. The free ligands and their
      corresponding ruthenium complexes all displayed photochromic properties with
      highly efficient conversion between the closed stable isomers (DHP) and their
      open forms (CPD). The properties of the compounds in their closed and open forms
      were investigated by cyclic voltammetry, spectroscopy, and luminescence
      measurements.

PMID- 21853970
TI  - Tuning of the spin distribution between ligand- and metal-based spin: electron
      paramagnetic resonance of mixed-ligand molybdenum tris(dithiolene) complex
      anions.
AB  - Electron paramagnetic resonance spectra of homoleptic and mixed-ligand molybdenum
      tris(dithiolene) complex anions [Mo(tfd)(m)(bdt)(n)](-) (n + m = 3; bdt =
      S(2)C(6)H(4); tfd = S(2)C(2)(CF(3))(2)) reveal that the spin density has mixed
      metal-ligand character with more ligand-based spin for [Mo(tfd)(3)](-) and a
      higher degree of metal-based spin for [Mo(bdt)(3)](-): the magnitude of the
      isotropic (95,97)Mo hyperfine interaction increases continuously, by a factor of
      2.5, on going from the former to the latter. The mixed complexes fall in between,
      and the metal character of the spin increases with the bdt content. The
      experiments were corroborated by density functional theory computations, which
      reproduce this steady increase in metal-based character.

PMID- 21853974
TI  - Trinitrotoluene explosive lights up ultrahigh Raman scattering of nonresonant
      molecule on a top-closed silver nanotube array.
AB  - The highest Raman enhancement factors are obtained in a double resonance:
      molecular electronic resonance and plasmon resonance with a "hot spot" in surface
      enhanced Raman scattering (SERS). However, for most molecules of interest the
      double resonance is not realized with the excitation frequencies normally used in
      Raman. The latter may limit the practical applications of SERS for trace
      analysis. Here, we report that Raman-inactive trinitrotoluene (TNT) lights up the
      ultrahigh Raman scattering of off-resonated p-aminobenzenethiol (PABT) through
      the formation of charge-transfer TNT-PABT complex on the top-closed flexible
      silver nanotube array. Raman hot spots can spontaneously form in a reversible way
      by the self-approaching of flexible nanotubes driven through the capillary force
      of solvent evaporation. Meanwhile, the PABT-TNT-PABT bridges between self
      approaching silver nanotubes possibly form by the specific complexing and
      zwitterion interactions, and the resultant chromophores can absorb the visible
      light that matches with the incident laser and the localized surface plasmon of a
      silver nanotube array. The multiple spectral resonances lead to the huge
      enhancement of Raman signals of PABT molecules due to the presence of ultratrace
      TNT. The enhancement effect is repeatedly renewable by the reconstruction of
      molecular bridges and can selectively detect TNT with a limit of 1.5 * 10(-17) M.
      The results in this report provide the simple and supersensitive approach to the
      detection of TNT explosives and the possibility of building a robust Raman-based
      assay platform.

PMID- 21853971
TI  - Organocatalytic iminium ion/carbene reaction cascade for the formation of
      optically active 2,4-disubstituted cyclopentenones.
AB  - An organocatalytic iminium ion/N-heterocyclic carbene (NHC) cascade reaction
      between beta-keto phenyltetrazolesulfones and alpha,beta-unsaturated aldehydes,
      providing direct access to optically active 2,4-disubstituted cyclopent-2-enones,
      has been developed. The products are isolated in good yields with high
      enantioselectivities.

PMID- 21853975
TI  - Structure and magnetism of the quasi-1-d K4Cu(MoO4)3 and the structure of
      K4Zn(MoO4)3.
AB  - Single crystals of K(4)Cu(MoO(4))(3) and nonmagnetic K(4)Zn(MoO(4))(3) have been
      grown by the flux-growth method. K(4)Cu(MoO(4))(3) can be described as a quantum
      quasi-1-d antiferromagnet with correlations between neighboring Cu(2+) ions but
      no magnetic long-range ordering down to 0.4 K. Comparison of the structure and
      magnetic properties of isostructural A(4)Cu(MoO(4))(3) (A = K, Rb) allows the
      isolation of the effects of low dimensionality from structural distortion along
      the Cu-O-Mo chains. The characteristic one-dimensional behavior is hence
      suppressed to lower the temperature in K(4)Cu(MoO(4))(3) in comparison with that
      of the Rb analogue. For example, a broad peak in the specific heat is observed
      ~2.3 K at 0 T, which is consistent with the onset of the quantum spin liquid
      state.

PMID- 21853976
TI  - Comprehensive two-dimensional manipulations of picoliter microfluidic droplets
      sampled from nanoliter samples.
AB  - A facile method is presented for achieving comprehensive two-dimensional droplet
      manipulations in closed microstructures consisting of microwell arrays and a
      straight microchannel. In this method, picoliter/nanoliter droplets with
      controllable sizes and numbers are sampled from nanoliter samples/reagents with
      almost 100% efficiency. Droplet motions are precisely controlled in the +/-X
      direction and +/-Y-direction by managing hydrostatic pressure and magnetic
      repulsion, respectively. As a demonstration, a fluorescein-labeled droplet and a
      deionized droplet are successively generated and trapped in adjacent microwells.
      Then their positions are quickly exchanged without cross-contamination and fusion
      is implemented on-demand. After operations, hydrophobic ferrofluid can be
      completely replaced by mineral oil and droplets still remain in microwells
      safely. A typical fluorescence intensity-based assay is demonstrated: droplet
      arrays containing copper ion are diluted disproportionately first and then
      detected by addition of droplet arrays containing Calcein. With the ability of
      comprehensive two-dimensional droplet manipulations, this method could be used in
      various miniaturized biochemical analyses including requirements of multistep
      procedures and in situ monitoring.

PMID- 21853977
TI  - Three-dimensional spatial patterning of proteins in hydrogels.
AB  - The ability to create three-dimensional biochemical environments that mimic those
      in vivo is valuable for the elucidation of fundamental biological phenomena and
      pathways. To this end, we designed a system in which proteins can be
      photochemically patterned in three dimensions within hydrogels under
      physiological conditions. Fibroblast growth factor-2 (FGF2) was immobilized
      within agarose hydrogels that were modified with two-photon labile 6-bromo-7
      hydroxycoumarin-protected thiols. Two different methods were developed for FGF2
      immobilization. The first procedure relies on the protein containing free
      cysteines for the formation of disulfide bonds with photoexposed agarose thiols.
      The second procedure takes advantage of the femtomolar binding partners, human
      serum albumin (HSA) and albumin binding domain (ABD), which have K(D) values of
      ~10(-14) M. Here HSA-maleimide was chemically bound to photoexposed agarose
      thiols, and then the FGF2-ABD fusion protein was added to form a stable complex
      with the immobilized HSA. The use of orthogonal, physical binding pairs allows
      protein immobilization under mild conditions and can be broadly applied to any
      protein expressed as an ABD fusion.

PMID- 21853968
TI  - Total syntheses of (+)-vigulariol and (-)-sclerophytin A.
AB  - The total syntheses of (+)-vigulariol and (-)-sclerophytin A are reported in 15
      steps and 16 steps, respectively, from a known compound. The flexible, readily
      scalable synthetic strategy allows for rapid construction of a critical tricyclic
      intermediate and is demonstrated via the synthesis of these two marine natural
      products. A key reaction in this synthetic protocol is a combination
      Wittig/intramolecular Diels-Alder cycloaddition.

PMID- 21853979
TI  - Slow-dissociation and slow-recombination assumptions in nonequilibrium capillary
      electrophoresis of equilibrium mixtures.
AB  - Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) is a
      kinetic affinity method with both analytical and preparative applications. NECEEM
      requires that the dissociation of the complexes be negligible in its first phase
      and the recombination of the dissociated complexes be negligible in its second
      phase. Here, we introduce a method, which facilitates easy examination of whether
      or not these requirements are satisfied. We derived expressions for two
      parameters, termed the slow-dissociation parameter (SDP) and slow-recombination
      parameter (SRP), which can be used to assess the assumptions. Both parameters
      should be much less than 1 for the assumptions to be satisfied. We calculated the
      two parameters for new and previously published NECEEM experiments and found that
      the assumptions were satisfied in all of them. Finally, we discuss changes to
      NECEEM conditions that should be done if the assumptions are found not to be
      satisfied. The SDP/SRP assessment helps to easily validate the results of NECEEM
      based analyses and thus makes the NECEEM method more robust.

PMID- 21853973
TI  - Evidence for the presence of two conformations of the heme a3-Cu(B) pocket of
      cytochrome caa3 from Thermus thermophilus.
AB  - Resonance Raman (RR) and "light" minus "dark" Fourier transform infrared (FTIR)
      difference spectra are reported for the CO-bound caa(3) oxidase from Thermus
      thermophilus. Two Fe-CO stretching modes at 518 and 507 cm(-1), the Fe-C-O
      bending mode at 570 cm(-1), and three C-O modes of heme a(3) at 1958, 1967, and
      1973 cm(-1) have been identified in the RR and FTIR spectra, respectively. The
      FTIR "light" minus "dark" spectrum indicates the formation of Cu(B)CO as revealed
      by its nu(CO) at 2060/2065 cm(-1). We assign the bands at 518 (nu(Fe-CO)) and
      1967/1973 cm(-1) (nu(C-O)) as the alpha-conformation. We also assign the bands at
      507 and 1958 cm(-1) (nu(C-O)) as originating from the beta-conformation of the
      enzyme. A frequency upshift of the heme a(3) Fe-His mode is observed subsequent
      to CO photolysis from 209 cm(-1) in the equilibrium deoxy enzyme to 214 cm(-1) in
      the photoproduct. The caa(3) data, distinctly different from those of ba(3)
      oxidase, are discussed in terms of the coupling of the alpha- and beta
      conformations that occur in heme-copper oxidases with catalytic function. The
      dynamics between the heme a(3) and heme a propionates as revealed by the
      perturbation of the bending vibrations delta(prop) of hemes a and a(3) at 385 and
      392 cm(-1), respectively, induced upon CO binding to heme a(3) is discussed in
      terms of the protonic connectivity between the heme a ring-D propionate/Arg site
      with that of the heme a(3) ring-D propionate-H(2)O site that leads to the highly
      conserved in the heme-copper oxidases water pool.

PMID- 21853978
TI  - Model study of CO inhibition of [NiFe]hydrogenase.
AB  - We propose a modified mechanism for the inhibition of [NiFe]hydrogenase
      ([NiFe]H(2)ase) by CO. We present a model study, using a NiRu H(2)ase mimic, that
      demonstrates that (i) CO completely inhibits the catalytic cycle of the model
      compound, (ii) CO prefers to coordinate to the Ru(II) center rather than taking
      an axial position on the Ni(II) center, and (iii) CO is unable to displace a
      hydrido ligand from the NiRu center. We combine these studies with a reevaluation
      of previous studies to propose that, under normal circumstances, CO inhibits
      [NiFe]H(2)ase by complexing to the Fe(II) center.

PMID- 21853980
TI  - Detection of surface antigens on living cells through incorporation of
      immunorecognition into the distinct positioning of cells with positive and
      negative dielectrophoresis.
AB  - Rapid determination of surface antigens on cells is possible by immobilization of
      cells accumulated by positive dielectrophoresis (p-DEP) via effective surface
      immunoreactions and removal of unbound cells by negative DEP (n-DEP). The DEP
      device for cell manipulation comprises a microfluidic channel with an upper
      indium tin oxide (ITO) electrode and a lower ITO microband array electrode (band
      electrode) modified with an antibody. Cells with the surface antigen introduced
      into the channel immediately accumulated on the surface of the band electrode
      during p-DEP generated by the application of ac voltage between the ITO electrode
      and the band electrode to immobilize by the specific antibody. The removal of
      accumulated cells to the gap region during n-DEP was used for rapid estimation of
      the residual cells with a specific surface antigen. We demonstrate here that
      human promyelocytic leukemia cells with the surface antigen CD33 can be captured
      on a band electrode modified with anti-CD33 antibody. The time required for the
      determination of the surface antigen using this compelled accumulation of cells
      by p-DEP and the separation of unbound cells by n-DEP is decreased to 60 s
      compared to that required by a cell binding assay using microtiter plates (30
      min). Furthermore, the present method for a novel cell binding assay does not
      require pretreatment such as target labeling or washing of unbound cells and
      thereby enhancing throughput in the clinic and in cytobiology studies.

PMID- 21853981
TI  - Macroscopic and microscopic investigation of Ni(II) sequestration on diatomite by
      batch, XPS, and EXAFS techniques.
AB  - Sequestration of Ni(II) on diatomite as a function of time, pH, and temperature
      was investigated by batch, XPS, and EXAFS techniques. The ionic strength
      dependent sorption at pH < 7.0 was consistent with outer-sphere surface
      complexation, while the ionic strength-independent sorption at pH = 7.0-8.6 was
      indicative of inner-sphere surface complexation. EXAFS results indicated that the
      adsorbed Ni(II) consisted of ~6 O at R(Ni-O) ~ 2.05 A. EXAFS analysis from the
      second shell suggested that three phenomena occurred at the diatomite/water
      interface: (1) outer-sphere and/or inner-sphere complexation; (2) dissolution of
      Si which is the rate limiting step during Ni uptake; and (3) extensive growth of
      surface (co)precipitates. Under acidic conditions, outer-sphere complexation is
      the main mechanism controlling Ni uptake, which is in good agreement with the
      macroscopic results. At contact time of 1 h or 1 day or pH = 7.0-8.0, surface
      coprecipitates occur concurrently with inner-sphere complexes on diatomite
      surface, whereas at contact time of 1 month or pH = 10.0, surface
      (co)precipitates dominate Ni uptake. Furthermore, surface loading increases with
      temperature increasing, and surface coprecipitates become the dominant mechanism
      at elevated temperature. The results are important to understand Ni interaction
      with minerals at the solid-water interface, which is helpful to evaluate the
      mobility of Ni(II) in the natural environment.

PMID- 21853982
TI  - pH and reduction dual-sensitive copolymeric micelles for intracellular
      doxorubicin delivery.
AB  - This study develops novel pH and reduction dual-sensitive micelles for the
      anticancer drug doxorubicin (DOX) delivery owing to the fact that the tumor
      tissues show low pH and high reduction environment. These sub-100 nm micelles
      present a core-shell structure under physiological conditions, but quickly
      release the loaded drugs responding to acidic and reductive stimuli. With
      disulfide bonds in each repeat unit of poly(beta-amino ester)s, the novel
      copolymer was synthesized via Michael addition polymerization from 2,2'
      dithiodiethanol diacrylate, 4,4'-trimethylene dipiperidine, and methoxy-PEG
      NH(2). DOX released faster from micelles in a weakly acidic environment (pH 6.5)
      than at pH 7.4 or in the presence of a higher concentration (5 mM) of reducing
      agent (DTT). The release is even more effective in a scenario of both stimuli (pH
      6.5 and 5 mM DTT). MTT assay showed that the DOX-loaded micelles had a higher
      cytotoxicity for HepG2 tumor cells than DOX at higher concentrations, and that
      blank micelles had a very low cytotoxicity to the tumor cells. Confocal
      microscopy observation showed that the micelles can be quickly internalized,
      effectively deliver the drugs into nuclei, and inhibit cell growth. These results
      present the copolymer as a novel and effective pH and reduction dual-responsive
      nanocarrier to enhance drug efficacy for cancer cells.

PMID- 21853984
TI  - Chiral metamaterial composed of three-dimensional plasmonic nanostructures.
AB  - We introduce a top-down fabricated metamaterial composed of three-dimensional,
      chiral, plasmonic nanostructures for visible and near-infrared wavelengths. Based
      on a combined spectroscopic and interferometric characterization, the entire
      complex transmission response in terms of a Jones matrix is disclosed.
      Particularly, the polarization output state of light after propagation through
      the nanostructures can be decoded from the measurements for any excitation
      configuration. We experimentally found a rotation of the polarization azimuth of
      linearly polarized light exceeding 50 degrees  at wavelengths around 1.08 MUm.
      This corresponds to a specific rotation which is significantly larger than that
      of any linear, passive, and reciprocal medium reported to date.

PMID- 21853983
TI  - Heparin mimetic peptide nanofibers promote angiogenesis.
AB  - New blood vessel formation (angiogenesis) is one of the most important processes
      required for functional tissue formation. Induction of angiogenesis is usually
      triggered by growth factors released by cells. Glycosaminoglycans (e.g., heparan
      sulphates) in the extracellular matrix aid in proper functioning of these growth
      factors. Therefore, exogeneous heparin or growth factors were required for
      promoting angiogenesis in previous regenerative medicine studies. Here we report
      for the first time induction of angiogenesis by a synthetic nanofibrous peptide
      scaffold without the addition of any exogenous growth factors or heparin. We
      designed and synthesized a self-assembling peptide amphiphile molecule that is
      functionalized with biologically active groups to mimic heparin. Like heparin,
      this molecule has the ability to interact with growth factors and effectively
      enhance their bioactivity. The nanofibers formed by these molecules were shown to
      form a 3D network mimicking the structural proteins in the extracellular matrix.
      Because of heparin mimicking capabilities of the peptide nanofibers, angiogenesis
      was induced without the addition of exogenous growth factors in vitro. Bioactive
      interactions between the nanofibers and the growth factors enabled robust
      vascularization in vivo as well. Heparin mimetic peptide nanofibers presented
      here provide new opportunities for angiogenesis and tissue regeneration by
      avoiding the use of heparin and exogenous growth factors. The synthetic peptide
      nanofiber scaffolds enriched with proper chemical functional groups shown in this
      study can be used to induce various desired physiological responses for tissue
      regeneration.

PMID- 21853985
TI  - DNA nanostructure-decorated surfaces for enhanced aptamer-target binding and
      electrochemical cocaine sensors.
AB  - The sensitivity of aptamer-based electrochemical sensors is often limited by
      restricted target accessibility and surface-induced perturbation of the aptamer
      structure, which arise from imperfect packing of probes on the heterogeneous and
      locally crowded surface. In this study, we have developed an ultrasensitive and
      highly selective electrochemical aptamer-based cocaine sensor (EACS), based on a
      DNA nanotechnology-based sensing platform. We have found that the electrode
      surface decorated with an aptamer probe-pendant tetrahedral DNA nanostructure
      greatly facilitates cocaine-induced fusion of the split anticocaine aptamer. This
      novel design leads to a sensitive cocaine sensor with a remarkably low detection
      limit of 33 nM. It is also important that the tetrahedra-decorated surface is
      protein-resistant, which not only suits the enzyme-based signal amplification
      scheme employed in this work, but ensures high selectivity of this sensor when
      deployed in sera or other adulterated samples.

PMID- 21853986
TI  - Three-component, one-flask synthesis of rhodanines (thiazolidinones).
AB  - 5-(Z)-alkylidene-2-thioxo-1,3-thiazolidin-4-ones (rhodanine derivatives) were
      prepared by reaction of in situ generated dithiocarbamates with recently reported
      racemic alpha-chloro-beta,gamma-alkenoate esters. This multicomponent sequential
      transformation performed in one reaction flask represents a general route to this
      medicinally valuable class of sulfur/nitrogen heterocycles. Using this convergent
      procedure, we prepared an analogue of the drug epalrestat, an aldose reductase
      inhibitory rhodanine.

PMID- 21853988
TI  - Cellulosic biofuels disappoint.

PMID- 21853987
TI  - An abiotic analogue of the nuclear pore complex hydrogel.
AB  - We describe an abiotic hydrogel that mimics selectivity of the nuclear pore
      complex. Copolymerization of peptide tetramers (phenylalanine-serine
      phenylalanine-glycine, FSFG) with acrylamide results in hydrophobic interactions
      significant enough to allow the formation of freestanding hydrogel structures.
      Incorporation of FSFG motifs also renders the hydrogels selective. Selective
      binding of importins and nuclear transport receptor-cargo complexes is
      qualitatively demonstrated and compared with polyacrylamide, hydrogels prepared
      from a control peptide, and hydrogels prepared from the nuclear pore complex
      protein Nsp1. These abiotic hydrogels will enable further studies of the unique
      transport mechanisms of the nuclear pore complex and provide an interesting
      paradigm for the future development of synthetic platforms for separations and
      selective interfaces.

PMID- 21853989
TI  - Calorimetric study of water's glass transition in nanoscale confinement,
      suggesting a value of 210 K for bulk water.
AB  - At what temperature between 136 and 165 K the glass transition of water occurs is
      still controversial, while the crystallization of water prevents the
      determination. To confine water in nanopores stabilizes its liquid state down to
      low temperatures. Heat capacities and enthalpy relaxation effects of the water
      confined within MCM-41 nanopores with diameters in the range 1.5-5.0 nm were
      measured in this work by using adiabatic calorimetry. No fusion of the confined
      water was detected up to 2.0 nm, part of the water exhibited fusion in 2.1 nm
      pores, and the whole internal water which excludes the molecules interacting with
      the pore-wall atoms crystallized within pores with diameter of 2.3 nm and above.
      A glass transition of the internal water occurred at a temperature T(g) = 160-165
      K for pore diameters in the range 1.5-2.0 nm and at 205-210 K for diameters of
      2.0 and 2.1 nm; thus, the T(g) jumped from 165 to 205 K at 2.0 nm. The jump is
      connected to the development of hydrogen-bond network to a more complete one as
      the diameter is increased, and is conjectured as caused by the increase in the
      number, from three to four, of hydrogen bonds formed by each molecule. These
      imply that the glass transition of bulk water occurs at 210 K, which is much
      higher than 136 or 165 K debated so far.

PMID- 21853990
TI  - Ni5, Ni8, and Ni10 clusters with 2,6-diacetylpyridine-dioxime as a ligand.
AB  - In the present work, novel coordination possibilities for the system
      dapdoH(2)/Ni(II) (dapdoH(2) = 2,6-diacetylpyridine-dioxime) have been explored.
      Depending on the starting reagents and solution conditions, several clusters with
      nuclearities ranging from Ni(5) to Ni(10) were achieved and structurally
      characterized, namely, [Ni(5)(R
      COO)(2)(dapdo)(2)(dapdoH)(2)(N(CN)(2))(2)(MeOH)(2)] in which R-COO(-) = benzoate
      (1) or 3-chlorobenzoate (2), [Ni(8)(dapdo)(4)(NO(3))(4)(OH)(4)(MeOH)(4)] (3), and
      [Ni(10)(dapdo)(8)(N(CN)(2))(2)(MeO)(MeOH)](NO(3)) (4). For the first time,
      pentadentate coordination for the dapdo(2-) ligand has been established. All
      compounds show a combination of square-planar and octahedrally coordinated nickel
      atoms. According to the Ni(2)(sp)Ni(3)(Oh) (1 and 2), Ni(4)(sp)Ni(4)(Oh) (3), and
      Ni(4)(sp)Ni(6)(Oh) (4) environments, these systems magnetically behave as trimer,
      tetramer, and hexanuclear clusters, respectively. dc magnetic measurements in the
      2-300 K range of temperature reveal antiferromagnetic coupling for all compounds,
      and the correlation of the superexchange interaction with the torsion angles
      involving the oximato bridges is experimentally confirmed.

PMID- 21853991
TI  - Structural modification of honokiol, a biphenyl occurring in Magnolia
      officinalis: the evaluation of honokiol analogues as inhibitors of angiogenesis
      and for their cytotoxicity and structure-activity relationship.
AB  - Honokiol, widely known as an antitumor agent, has been used as an
      antiangiogenesis drug lead. In this paper, 47 honokiol analogues and derivatives
      were investigated for their antiangiogenic activity by application of the
      transgenic zebrafish screening model, antiproliferative and cytotoxic activity
      against HUVECs, and three tumor cell lines by MTT assay. 3',5-Diallyl-2,4'
      dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde (8c) was found to suppress the
      newly grown segmental vessels from the dorsal aorta of zebrafish and prevent
      inappropriate vascularization as well as exhibit more potent inhibitory effects
      on the proliferation of HUVECs, A549, HepG2, and LL/2 cells (IC(50) = 15.1, 30.2,
      10.7, and 21.7 MUM, respectively) than honokiol (IC(50) = 52.6, 35.0, 16.5, and
      65.4 MUM, respectively). Analogue 8c also effectively inhibited the migration and
      capillary-like tube formation of HUVECs in vitro. The antiangiogenic effect and
      antiproliferative activity of these structurally modified honokiol analogues and
      derivatives have led to the establishment of a structure-activity relationship.

PMID- 21853992
TI  - Control of structural, electronic, and optical properties of eumelanin films by
      electrospray deposition.
AB  - The capability to monitor finely the physical properties of eumelanin, an
      important class of biopolymers, involved in melanoma cancer pathologies, whose
      function and intrinsic disorder still collects the interest of many
      investigators, was achieved by means of electrospray deposition (ESD). By
      alleviating the problem of the solubility of melanin through the realization of
      high-quality films it was possible to spread light on the unknown biopolymer
      supramolecular organization. In fact, on the basis of scanning probe
      microscopies, electron spectroscopies, and transport properties, it was possible
      to delineate peculiar features of the melanin organization varying from
      heteropolymeric to oligomeric in character and eventually turning in a cross
      linked secondary molecular structure.

PMID- 21853993
TI  - Tailored microarray platform for the detection of marine toxins.
AB  - Currently, there are no fast in vitro broad spectrum screening bioassays for the
      detection of marine toxins. The aim of this study was to develop such an assay.
      In gene expression profiling experiments 17 marker genes were provisionally
      selected that were differentially regulated in human intestinal Caco-2 cells upon
      exposure to the lipophilic shellfish poisons azaspiracid-1 (AZA1) or dinophysis
      toxin-1 (DTX1). These 17 genes together with two control genes were the basis for
      the design of a tailored microarray platform for the detection of these marine
      toxins and potentially others. Five out of the 17 selected marker genes on this
      dedicated DNA microarray gave clear signals, whereby the resulting fingerprints
      could be used to detect these toxins. CEACAM1, DDIT4, and TUBB3 were up-regulated
      by both AZA1 and DTX1, TRIB3 was up-regulated by AZA1 only, and OSR2 by DTX1
      only. Analysis by singleplex qRT-PCR revealed the up- and down-regulation of the
      selected RGS16 and NPPB marker genes by DTX1, that were not envisioned by the new
      developed dedicated array. The qRT-PCR targeting the DDIT4, RSG16 and NPPB genes
      thus already resulted in a specific pattern for AZA1 and DTX1 indicating that for
      this specific case qRT-PCR might a be more suitable approach than a dedicated
      array.

PMID- 21853994
TI  - Different EDC/NHS activation mechanisms between PAA and PMAA brushes and the
      following amidation reactions.
AB  - Infrared spectroscopy was applied to investigate the well-known EDC/NHS (N-ethyl
      N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) activation details
      of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) brushes grafted on
      porous silicon. Succinimidyl ester (NHS-ester) is generally believed to be the
      dominant intermediate product, conveniently used to immobilize biomolecules
      containing free primary amino groups via amide linkage. To our surprise, the
      infrared spectral details revealed that the EDC/NHS activation of PMAA generated
      anhydride (estimated at around 76% yield and 70% composition), but not NHS-ester
      (around 5% yield and 11% composition) under the well-documented reaction
      conditions, as the predominant intermediate product. In contrast, EDC/NHS
      activation of PAA still follows the general rule, i.e., the expected NHS-ester is
      the dominant intermediate product (around 45% yield and 57% composition),
      anhydride the side product (40% yield and 28% composition), under the optimum
      reaction conditions. The following amidation on PAA-based NHS-esters with a model
      amine-containing compound, L-leucine methyl ester, generated approximately 70%
      amides and 30% carboxylates. In contrast, amidation of PAA- or PMAA-based
      anhydrides with L-leucine methyl ester only produced less than 30% amides but
      more than 70% carboxylates. The above reaction yields and percentage compositions
      were estimated by fitting the carbonyl stretching region with 5 possible species,
      NHS-ester, anhydride, N-acylurea, unreacted acid, unhydrolyzed tert-butyl ester,
      and using the Beer-Lambert law. The different surface chemistry mechanisms will
      bring significant effects on the performance of surface chemistry-derived devices
      such as biochips, biosensors, and biomaterials.

PMID- 21853995
TI  - Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of
      HIV reverse transcriptase.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the
      replication of human immunodeficiency virus (HIV) are being pursued with guidance
      from molecular modeling including free-energy perturbation (FEP) calculations for
      protein-inhibitor binding affinities. The previously reported
      pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents;
      they inhibit replication of wild-type HIV-1 in infected human T-cells with EC(50)
      values of 2 and 10 nM, respectively. However, they show no activity against viral
      strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates
      that the problem is likely associated with extensive interaction between the
      dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is
      computed to be oriented in a manner diminishing the contact with Tyr181. However,
      this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 MUM).
      The present report details the efficient, computationally driven evolution of 3
      to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C
      containing variants. The critical contributors were FEP substituent scans for the
      phenoxy and pyrimidine rings and recognition of potential benefits of addition of
      a cyanovinyl group to the phenoxy ring.

PMID- 21853997
TI  - A facile synthesis, in vitro and in vivo MR studies of d-glucuronic acid-coated
      ultrasmall Ln2O3 (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles as a new potential
      MRI contrast agent.
AB  - A facile one-pot synthesis of d-glucuronic acid-coated ultrasmall Ln(2)O(3) (Ln =
      Eu, Gd, Dy, Ho, and Er) nanoparticles is presented. Their water proton
      relaxivities were studied to address their possibility as a new potential MRI
      contrast agent. We focused on the d-glucuronic acid-coated ultrasmall Dy(2)O(3)
      nanoparticle because it showed the highest r(2) relaxivity among studied
      nanoparticles. Its performance as a T(2) MRI contrast agent was for the first
      time proved in vivo through its 3 T T(2) MR images of a mouse, showing that it
      can be further exploited for the rational design of a new T(2) MRI contrast agent
      at high MR fields.

PMID- 21853998
TI  - Tunneling currents that increase with molecular elongation.
AB  - We present a model molecular system with an unintuitive transport-extension
      behavior in which the tunneling current increases with forced molecular
      elongation. The molecule consists of two complementary aromatic units (1,4
      anthracenedione and 1,4-anthracenediol) hinged via two ether chains and attached
      to gold electrodes through thiol-terminated alkenes. The transport properties of
      the molecule as it is mechanically elongated in a single-molecule pulling setting
      are computationally investigated using a combination of equilibrium molecular
      dynamics simulations of the pulling with gDFTB computations of the transport
      properties in the Landauer limit. Contrary to the usual exponential decay of
      tunneling currents with increasing molecular length, the simulations indicate
      that upon elongation electronic transport along the molecule increases 10-fold.
      The structural origin of this inverted trend in the transport is elucidated via a
      local current analysis that reveals the dual role played by H-bonds in both
      stabilizing pi-stacking for selected extensions and introducing additional
      electronic couplings between the complementary aromatic rings that also enhance
      tunneling currents across the molecule. The simulations illustrate an inverted
      electromechanical single-molecule switch that is based on a novel class of
      transport-extension behavior that can be achieved via mechanical manipulation and
      highlight the remarkable sensitivity of conductance measurements to the molecular
      conformation.

PMID- 21853996
TI  - Investigating Deinococcus radiodurans RecA protein filament formation on double
      stranded DNA by a real-time single-molecule approach.
AB  - With the aid of an efficient, precise, and almost error-free DNA repair system,
      Deinococcus radiodurans can survive hundreds of double-strand breaks inflicted by
      high doses of irradiation or desiccation. RecA of D. radiodurans (DrRecA) plays a
      central role both in the early phase of repair by an extended synthesis-dependent
      strand annealing process and in the later more general homologous recombination
      phase. Both roles likely require DrRecA filament formation on duplex DNA. We have
      developed single-molecule tethered particle motion experiments to study the
      assembly dynamics of RecA proteins on individual duplex DNA molecules by
      observing changes in DNA tether length resulting from RecA binding. We
      demonstrate that DrRecA nucleation on double-stranded DNA is much faster than
      that of Escherichia coli RecA protein (EcRecA), but the extension is slower. This
      combination of attributes would tend to increase the number and decrease the
      length of DrRecA filaments relative to those of EcRecA, a feature that may
      reflect the requirement to repair hundreds of genomic double-strand breaks
      concurrently in irradiated Deinococcus cells.

PMID- 21853999
TI  - Templated photocatalytic synthesis of well-defined platinum hollow nanostructures
      with enhanced catalytic performance for methanol oxidation.
AB  - Hollow metallic nanostructures exhibit important applications in catalysis,
      sensing, and phototherapy due to their increased surface areas, reduced
      densities, and unique optical and electronic features. Here we report a facile
      photocatalytic process to synthesize and tune hollow platinum (Pt)
      nanostructures. Through hierarchically structured templates, well-defined hollow
      Pt nanostructures are achieved. These nanostructures possess interconnected
      nanoporous framework as shell with high surface area for enhanced catalytic
      performance/mass transport for methanol oxidation.

PMID- 21854001
TI  - Shape-independent lateral force calibration.
AB  - Current methods for lateral force calibration are often time-consuming,
      expensive, or cause significant wear of the tip. A quick and simple alternative
      is presented in which the linear relationship between force and voltage is
      exploited. The technique is independent of the shapes of the sample and
      cantilever and eliminates common problems, while maintaining better than 10%
      precision. This advance will facilitate quantitative comparisons between
      experiments.

PMID- 21854000
TI  - Synthesis and properties of vermiculite-reinforced polyurethane nanocomposites.
AB  - Natural vermiculite was modified by cation exchange with long-chain quaternary
      alkylammonium salts and then dispersed in polyether-based polyols with different
      structures and ethylene oxide/propylene oxide ratios. The dispersions were
      evaluated by X-ray scattering and rheology. In all polyol dispersions tested,
      polyols were intercalated into the vermiculite interlayers. Also, significant
      shear thinning behavior was observed. A large interlayer spacing of ~90 A was
      achieved in one polyol suitable for polyurethane elastomer synthesis. In
      polyurethane made with this polyol, clay platelets were extensively intercalated
      or exfoliated. The composites showed a >270% increase in tensile modulus, >60%
      increase in tensile strength, and a 30% reduction in N(2) permeability with a
      loading of 5.3 wt % clay in polyurethane. Differential scanning calorimetry and
      dynamic mechanical analysis revealed that the nanoclay interacts with the
      polyurethane hard segments.

PMID- 21854002
TI  - Effect of urea on the beta-hairpin conformational ensemble and protein
      denaturation mechanism.
AB  - Despite the daily use of urea to influence protein folding and stability, the
      molecular mechanism with which urea acts is still not well understood. Here the
      use of combined parallel tempering and metadynamics simulation allows us to study
      the free-energy landscape associated with the folding/unfolding of beta-hairpin
      GB1 equilibrium in 8 M urea and pure water. The nature of the unfolded state in
      both solutions has been analyzed: in urea solution the addition of denaturants
      acts to expand the denatured state, while in pure water solution the unfolded
      state is noticeably more compact. For what concerns the mechanism by which urea
      acts as a denaturant, a preferential direct interaction between urea molecules
      and protein backbone has been found. However, the bias toward urea solvation is
      largest at intermediate values of the gyration radius.

PMID- 21854003
TI  - Influence of the covalent heme-protein bonds on the redox thermodynamics of human
      myeloperoxidase.
AB  - Myeloperoxidase (MPO) is the most abundant neutrophil enzyme and catalyzes
      predominantly the two-electron oxidation of ubiquitous chloride to generate the
      potent bleaching hypochlorous acid, thus contributing to pathogen killing as well
      as inflammatory diseases. Its catalytic properties are closely related with
      unique posttranslational modifications of its prosthetic group. In MPO, modified
      heme b is covalently bound to the protein via two ester linkages and one
      sulfonium ion linkage with a strong impact on its (electronic) structure and
      biophysical and chemical properties. Here, the thermodynamics of the one-electron
      reduction of the ferric heme in wild-type recombinant MPO and variants with
      disrupted heme-protein bonds (M243V, E242Q, and D94V) have been investigated by
      thin-layer spectroelectrochemistry. It turns out that neither the oligomeric
      structure nor the N-terminal extension in recombinant MPO modifies the peculiar
      positive reduction potential (E degrees ' = 0.001 V at 25  degrees C and pH 7.0)
      or the enthalpy or entropy of the Fe(III) to Fe(II) reduction. By contrast, upon
      disruption of the MPO-typical sulfonium ion linkage, the reduction potential is
      significantly lower (-0.182 V). The M243V mutant has an enthalpically stabilized
      ferric state, whereas its ferrous form is entropically favored because of the
      loss of rigidity of the distal H-bonding network. Exchange of an adjacent ester
      bond (E242Q) induced similar but less pronounced effects (E degrees ' = -0.094
      V), whereas in the D94V variant (E degrees ' = -0.060 V), formation of the
      ferrous state is entropically disfavored. These findings are discussed with
      respect to the chlorination and bromination activity of the wild-type protein and
      the mutants.

PMID- 21854004
TI  - Whole genome expression in peripheral-blood samples of workers professionally
      exposed to polycyclic aromatic hydrocarbons.
AB  - This study aims to examine global gene expression profiles before and after the
      work-shift among coke-oven workers (COWs). COWs work six consecutive days and
      then take two days off. Two blood and urine samples in each worker were collected
      before starting to work after two days off and end-of-shift in the sixth day of
      work in 2009. Altered gene expressions (ratio of gene expression levels between
      end-of-shift and preshift work) were performed by a Human OneArray expression
      system which probes ~30,000-transcription expression profiling of human genes.
      Sixteen workers, all men, were enrolled in this study. Median urinary 1
      hydroxypyrene (1OHP) levels (MUmol/mol creatinine) in end-of-shift work were
      significantly higher than those in preshift work (2.58 vs 0.29, p = 0.0002).
      Among the 20,341 genes which passed experimental quality control, 26 gene
      expression changes, 7 positive and 19 negative, were highly correlated with
      across-the-shift urinary 1OHP levels (end-of-shift-preshift 1OHP) (p-value
      <0.001). The high and low exposure groups of across-the-shift urinary 1OHP levels
      dichotomized in ~2.00 MUmol/mol creatinine were able to be distinguished by these
      26 genes. Some of them are known to be involved in apoptosis, chromosome
      stability/DNA repair, cell cycle control/tumor suppressor, cell adhesion,
      development/spermatogenesis, immune function, and neuronal cell function. These
      findings in COWs will be an ideal model to study the relationship of PAH exposure
      with acute changes of gene expressions.

PMID- 21854005
TI  - Aqueous-phase OH oxidation of glyoxal: application of a novel analytical approach
      employing aerosol mass spectrometry and complementary off-line techniques.
AB  - Aqueous-phase chemistry of glyoxal may play an important role in the formation of
      highly oxidized secondary organic aerosol (SOA) in the atmosphere. In this work,
      we use a novel design of photochemical reactor that allows for simultaneous photo
      oxidation and atomization of a bulk solution to study the aqueous-phase OH
      oxidation of glyoxal. By employing both online aerosol mass spectrometry (AMS)
      and offline ion chromatography (IC) measurements, glyoxal and some major products
      including formic acid, glyoxylic acid, and oxalic acid in the reacting solution
      were simultaneously quantified. This is the first attempt to use AMS in kinetics
      studies of this type. The results illustrate the formation of highly oxidized
      products that likely coexist with traditional SOA materials, thus, potentially
      improving model predictions of organic aerosol mass loading and degree of
      oxidation. Formic acid is the major volatile species identified, but the
      atmospheric relevance of its formation chemistry needs to be further
      investigated. While successfully quantifying low molecular weight organic
      oxygenates and tentatively identifying a reaction product formed directly from
      glyoxal and hydrogen peroxide, comparison of the results to the offline total
      organic carbon (TOC) analysis clearly shows that the AMS is not able to
      quantitatively monitor all dissolved organics in the bulk solution. This is
      likely due to their high volatility or low stability in the evaporated solution
      droplets. This experimental approach simulates atmospheric aqueous phase
      processing by conducting oxidation in the bulk phase, followed by evaporation of
      water and volatile organics to form SOA.

PMID- 21854006
TI  - Templating of self-alignment patterns of anisotropic gold nanoparticles on
      ordered SWNT macrostructures.
AB  - We report a simple and versatile technique for oriented assembly of gold nanorods
      on aligned single-walled carbon nanotube (SWNT) macrostructures, such as thin
      nanotube films and nanotube fibers. The deposition and assembly is accomplished
      via drop drying of dilute gold nanorod suspensions on SWNT macrostructures under
      ambient conditions. Guided by anisotropic interactions, gold nanorods, and
      polygonal platelets spontaneously align with SWNTs, resulting in macroscopic
      arrays of locally ordered nanorods supported on aligned SWNT substrates. SEM
      reveals that the scalar order parameter of rods relative to the local average
      SWNT alignment is 0.7 for rods on SWNT films and 0.9 for rods on SWNT fibers.
      This self-alignment is enabled by anisotropic gold nanoparticle-SWNT interactions
      and is observed for a wide range of nanoparticles, including nanorods with aspect
      ratios ranging from 2-35, thin gold triangular and other polygonal platelets. The
      plasmonic properties of aligned gold nanorods together with superior electronic,
      chemical and mechanical properties of SWNTs make these hybrid nanocomposites
      valuable for the design of self-assembled multifunctional optoelectronic
      materials and optical metamaterials.

PMID- 21854007
TI  - Identifying the research and infrastructure needs for the global assessment of
      hazardous chemicals ten years after establishing the Stockholm Convention.

PMID- 21854008
TI  - Z-selective, catalytic internal alkyne semihydrogenation under H2/CO mixtures by
      a niobium(III) imido complex.
AB  - The discovery of a Nb(III)-mediated catalytic hydrogenation of internal alkynes
      to (Z)-alkenes that proceeds through an unprecedented mechanism is reported. The
      mechanistic proposal involves initial reduction of the alkyne by the Nb(III)
      complex (BDI)Nb(N(t)Bu)(CO)(2) to provide a Nb(V) metallacyclopropene, itself
      capable of sigma-bond metathesis reactivity with H(2). The resulting alkenyl
      hydride species then undergoes reductive elimination to provide the (Z)-alkene
      product and regenerate a metal complex in the Nb(III) oxidation state. Support
      for the proposed mechanism is derived from (i) the dependence of the product
      selectivity on the relative concentrations of CO and H(2), (ii) the isolation of
      complexes closely related to those proposed to be part of the catalytic cycle,
      (iii) H/D crossover experiments, and (iv) DFT studies of multiple possible
      reaction pathways.

PMID- 21854010
TI  - Molecular basis for the inhibition of HMGA1 proteins by distamycin A.
AB  - The molecular mechanism for the displacement of HMGA1 proteins from DNA is
      integral to disrupting their cellular function, which is linked to many
      metastatic cancers. Chemical shift and NOESY NMR experiments provide structural
      evidence for the displacement of an AT hook peptide (DNA binding motif of HMGA1
      proteins) by both monomeric and dimeric distamycin. However, the displaced AT
      hook alters distamycin binding by weakening the distamycin:DNA complex, while
      slowing monomeric distamycin dissociation when AT hook is in excess. The central
      role of the AT hook was evaluated by monitoring full-length HMGA1a protein
      binding using fluorescence anisotropy. HMGA1a was effectively displaced by
      distamycin, but the cooperative binding exhibited by distamycin was eliminated by
      displaced HMGA1a. Additionally, these studies indicate that HMGA1a is displaced
      from the DNA by 1 equiv of distamycin, suggesting the ability to develop
      therapeutics that take advantage of the positively cooperative nature of HMGA1a
      binding.

PMID- 21854011
TI  - Palladium-catalyzed annulation reactions for diastereoselective cyclopentene
      synthesis.
AB  - Palladium-catalyzed annulation reactions of conjugate acceptors and allenyl
      boronic ester provide substituted cyclopentenes in high yields and, where
      applicable, diastereoselectivities. This method provides rapid assembly of
      building blocks for natural product synthesis, including polycyclic lactone and
      lactam products. Reactions are hypothesized to initiate by conjugate addition of
      a nucleophilic propargylpalladium complex.

PMID- 21854012
TI  - Intramolecular aryne-ene reaction: synthetic and mechanistic studies.
AB  - Although the chemistry of arynes is well developed, some challenges still remain.
      The ene reaction of arynes has not gained widespread use in synthesis as a result
      of poor yields and selectivity. A general, high yielding and selective
      intramolecular aryne-ene reaction is described providing various benzofused carbo
      and heterocycles. Mechanistic data is presented, and a rationale for the
      resulting stereochemistry is discussed.

PMID- 21854013
TI  - Interdependence of conformational and chemical reaction dynamics during ion
      assembly in polar solvents.
AB  - We have utilized time-resolved vibrational spectroscopy to study the
      interdependence of the conformational and chemical reaction dynamics of ion
      assembly in solution. We investigated the chemical interconversion dynamics of
      the LiNCS ion pair and the (LiNCS)(2) ion-pair dimer, as well as the spectral
      diffusion dynamics of these ionic assemblies. For the strongly coordinating Lewis
      base solvents benzonitrile, dimethyl carbonate, and ethyl acetate, we observe
      Li(+) coordination by both solvent molecules and NCS(-) anions, while the weak
      Lewis base solvent nitromethane shows no evidence for solvent coordination of
      Li(+) ions. The strong interaction between the ion-pair dimer structure and the
      Lewis base solvents leads to ion-pair dimer solvation dynamics that proceed more
      slowly than the ion-pair dimer dissociation. We have attributed the slow spectral
      diffusion dynamics to electrostatic reorganization of the solvent molecules
      coordinated to the Li(+) cations present in the ion-pair dimer structure and
      concluded that the dissociation of ion-pair dimers depends more critically on
      longer length scale electrostatic reorganization. This unusual inversion of the
      conformational and chemical reaction rates does not occur for ion-pair dimer
      dissociation in nitromethane or for ion pair association in any of the solvents.

PMID- 21854014
TI  - Electron and hydrogen transfer in small hydrogen fluoride anion clusters.
AB  - A new stable structure has been found for the anion clusters of hydrogen
      fluoride. The ab initio method was used to optimize the structures of the
      (HF)(3)(-), (HF)(4)(-), (HF)(5)(-), and (HF)(6)(-) anion clusters with an excess
      "solvated" electron. Instead of the well-known "zig-zag" (HF)(n)(-) structure, a
      new form, (HF)(n-1)F(-)...H, was found with lower energy. In this new form, the
      terminal hydrogen atom in the (HF)(n)(-) chain is separated from the other part
      of the cluster and the inner hydrogens transfer along the hydrogen bonds toward
      the outside fluoride. The negative charge also transfers from the terminal HF
      molecule of the chain to the center fluoride atoms. The (HF)(n)(-) clusters for n
      = 4, 5, and 6 have not yet been observed experimentally. These results should
      assist in the search for these systems and also provide a possible way to study
      the proton and electron transfer in some large hydrogen bonding systems.

PMID- 21854016
TI  - Asymmetric vinylogous Mannich reactions: a versatile approach to functionalized
      heterocycles.
AB  - Asymmetric vinylogous Mannich reaction (VMR) of 2-(tert
      butyldimethylsilyloxy)furan (TBSOF, 1) with (R(S))- or (S(S))-t-BS-imines (3)
      furnished 5-aminoalkylbutenolides 7a-k in 75-87% yields with anti/syn ratios
      ranging from 75:25 to 97:3. Butenolides 7a-f,k were readily converted into
      substituted lactones 8 and 5 and 6-substituted 5-hydroxypiperidin-2-ones 11a-g,
      which are, in turn, key intermediates for the synthesis of many bioactive
      compounds.

PMID- 21854018
TI  - Detection of weak absorption changes from molecular events in time-resolved FT-IR
      spectromicroscopy measurements of single functional cells.
AB  - The possibility of performing FT-IR spectromicroscopy experiments on individual
      living cells is the focus of considerable attention. Among the applications of
      interest, the obtainment of structural information in rapid measurements, with a
      time resolution of the minute or better, is a prized goal. In this work, we show
      that the use of synchrotron FT-IR spectromicroscopy allows one to extract weak
      spectral changes, of less than 10(-3) au per minute, in the absorption spectrum
      of single rod cells following photostimulation. We also show that absorption
      changes are accompanied by other optical effects due to changes in the real part
      of the refractive index of the cell. The use of two-dimensional correlation
      spectroscopy allows us to assign bands to specific molecular chromophores and to
      extract weak spectral variations in the presence of a noisy background.

PMID- 21854017
TI  - Reappraising the structures and distribution of metabolites from black aspergilli
      containing uncommon 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one
      systems.
AB  - To date, natural products containing 2-benzyl-4H-pyran-4-one and 2-benzylpyridin
      4(1H)-one substructures have been encountered in relatively few fungi outside of
      the black aspergilli clade. While exploring the occurrence of these compounds
      among Aspergillus spp., it was determined that the structures of the unusual
      furopyrrols tensidols A and B (5 and 6) and JBIR-86 and JBIR-87 (9 and 10) were
      incorrect and should be reassigned as 2-benzyl-4H-pyran-4-ones (7, 8, 11e, and
      12, respectively). The origin of the unique N-phenyl groups in the 2
      benzylpyridin-4(1H)-ones nygerones A and B (1 and 2) were also examined, and it
      was established that N-phenylamides added to the culture medium were suitable
      substrates for generating these metabolites; however, this phenomenon remained
      limited to a single fungus in our collection (Aspergillus niger ATCC 1015). A
      variety of 2-benzyl-4H-pyran-4-ones and 2-benzylpyridin-4(1H)-ones were detected
      among the black aspergilli, but only pestalamide B (13) was found in all 11 of
      the tested strains. These metabolites, as well as a group of synthetic analogues,
      demonstrated weak antifungal activity against several Candida strains,
      Aspergillus flavus, and Aspergillus fumigatus.

PMID- 21854020
TI  - An oxidative [2,3]-sigmatropic rearrangement of allylic hydrazides.
AB  - The development of an efficient oxidative [2,3]-sigmatropic rearrangement of
      allylic hydrazides, via singlet N-nitrene intermediates, is reported. The
      requisite allylic hydrazide precursors are readily prepared and undergo smooth
      sigmatropic rearrangement upon exposure to iodosobenzene. The products of this
      novel transformation are shown to be useful precursors to a variety of compounds.

PMID- 21854019
TI  - Preparation of lignopolyols from wheat straw soda lignin.
AB  - Wheat straw soda lignin was modified and characterized by several qualitative and
      quantitative methods such as (31)P NMR spectroscopy to evaluate its potential as
      a substitute for polyols in view of polyurethane applications. Chemical
      modification of the lignin was achieved with propylene oxide to form lignopolyol
      derivatives. This was performed by a two-step reaction of lignin with maleic
      anhydride followed by propylene oxide and by direct oxyalkylation under acidic
      and alkaline conditions. The physical and chemical properties of lignopolyols
      from each method and the subsequent chain-extended hydroxyl groups were
      evaluated. Direct oxyalkylation of lignin under alkaline conditions was found to
      be more efficient than acidic conditions and more effective than the two-step
      process for preparing lignopolyol with higher aliphatic hydroxyl contents.

PMID- 21854022
TI  - The cause for tremendous acceleration of chloride substitution via base catalysis
      in the chloro pentaammine cobalt(III) ion.
AB  - The base hydrolysis reaction of Co(NH(3))(5)Cl(2+) was investigated using density
      functional theory and molecular orbital methods. Geometries and energies of
      conjugate bases, intermediates, transition states, and minimum energy crossing
      points were computed. For the base hydrolysis of Co(NH(3))(5)Cl(2+), three
      pathways might operate: the mechanism proposed by Basolo and Pearson, the
      mechanism via a hexacoordinated intermediate exhibiting a triplet ground state,
      and a fully stereomobile I(d) mechanism. The hexacoordinated intermediate can
      lose the leaving ligand readily to form a square pyramidal pentacoordinated
      intermediate with a triplet state, which interconverts rapidly and reversibly
      into the Basolo-Pearson trigonal bipyramid with a singlet state. Due to its high
      activation energy, a stereochemical rearrangement via a Berry pseudorotation does
      not take place. The intermediates are not protonated because their pK(a) values
      are ~5 for the hexacoordinated intermediate and ~-6 for the trigonal bipyramidal
      pentacoordinated intermediate. The Basolo-Pearson mechanism proceeds with 50%
      stereoretention and 50% stereomobility. In the case that the hexacoordinated
      intermediate converts into the trigonal bipyramid, products with the same
      stereochemistry would be obtained. If, however, for the square pyramidal
      intermediate with a triplet state the entering ligand competes efficiently with
      the rearrangement into the trigonal bipyramid or if the substitution takes place
      at the hexacoordinated intermediate via, e.g., the I(d) mechanism, the reaction
      would proceed with retention of the configuration. Direct substitution via the
      I(d) mechanism, operating for azide and to a small extent also for water, is
      fully stereomobile. Computations on the Basolo-Pearson mechanism have also been
      performed for the chloro pentaammine complexes of chromium(III), ruthenium(III),
      and rhodium(III). This pathway might operate for chromium(III) but not for
      ruthenium(III) and rhodium(III).

PMID- 21854021
TI  - Real-space mapping of Fano interference in plasmonic metamolecules.
AB  - An unprecedented control of the spectral response of plasmonic nanoantennas has
      recently been achieved by designing structures that exhibit Fano resonances. This
      new insight is paving the way for a variety of applications, such as biochemical
      sensing and surface-enhanced Raman spectroscopy. Here we use scattering-type near
      field optical microscopy to map the spatial field distribution of Fano modes in
      infrared plasmonic systems. We observe in real space the interference of narrow
      (dark) and broad (bright) plasmonic resonances, yielding intensity and phase
      toggling between different portions of the plasmonic metamolecules when either
      their geometric sizes or the illumination wavelength is varied.

PMID- 21854023
TI  - Directed placement of gold nanorods using a removable template for guided
      assembly.
AB  - We have used a temperature sensitive polymer film as a removable template to
      position, and align, gold nanorods onto an underlying target substrate. Shape
      matching guiding structures for the assembly of nanorods of size 80 nm * 25 nm
      have been written by thermal scanning probe lithography. The nanorods were
      assembled into the guiding structures, which determine both the position and the
      orientation of single nanorods, by means of capillary interactions. Following
      particle assembly, the polymer was removed cleanly by thermal decomposition and
      the nanorods are transferred to the underlying substrate. We have thus
      demonstrated both the placement and orientation of nanorods with an overall
      positioning accuracy of ~10 nm onto an unstructured target substrate.

PMID- 21854024
TI  - Electronic structure, molecular electrostatic potentials, vibrational spectra in
      substituted calix[n]arenes (n = 4, 5) from density functional theory.
AB  - Electronic structure, molecular electrostatic potential, and vibrational
      frequencies of para-substituted calix[n]arene CX[n]-R (n = 4, 5; R = H, NH(2), t
      Bu, CH(2)Cl, SO(3)H, NO(2)) and their thia analogs (S-CX[n]-R; with R = H and t
      Bu) in which sulfur bridges two aromatic rings of CX[n] have been derived from
      the density functional theory. A rotation around CH(2) groups connecting the
      phenol rings engenders four, namely, cone, partial cone, 1,2-alternate, and 1,3
      alternate CX[n]-R conformers. Of these, the cone conformer comprising of large
      number of O1-H1...O1' interactions turns out to be of lowest energy. Normal
      vibration analysis reveal the O1-H1 stretching frequency of unsubstituted CX[n]
      shifts to higher wavenumber (blue shift) on substitution of electron-withdrawing
      (NO(2) or SO(3)H) groups, while electron-donating substituents (NH(2), t-Bu)
      engender a shift of O1-H1 vibration in the opposite direction (red shift). The
      direction of frequency shifts have been analyzed using natural bond orbital
      analysis and molecular electrostatic potential (MESP) topography. Furthermore,
      calculated (1)H NMR chemical shift (delta(H)) in modified CX[n] hosts follow the
      order: H1 > H3/H5 > H7(a) > H7(b). The delta(H) values in CX[4] are in consonant
      with the observed (1)H NMR spectra.

PMID- 21854025
TI  - Investigation of the emission mechanism in milled SrAl2O4:Eu, Dy using optical
      and synchrotron X-ray spectroscopy.
AB  - There currently exists much debate as to the active state related to the "long
      afterglow" effect in europium doped oxide materials. Redox couples that consist
      of Eu(+/2+) and Eu(2+/3+) are discussed, but no common answer is currently
      accepted. Here, we present a comparison of the optical properties of a
      commercially available SrAl(2)O(4):Eu, Dy phosphor, as a function of nanoparticle
      size reduction via dry mechanical milling. X-ray and optical spectroscopic data
      indicate a significant decrease in phosphorescence efficiency and an increase in
      laser stimulated emission efficiency as near surface Eu(2+) ions are oxidized to
      Eu(3+) as a consequence of increased exposure during the milling process. These
      results show evidence only for Eu(2+/3+) oxidation states, suggesting the
      mechanism related to long afterglow effect does not arise from Eu(+) species. We
      also suggest that size reduction, as a rule, cannot be universally applied to
      improve optical properties of nanostructures.

PMID- 21854026
TI  - Two-level conductance fluctuations of a single-molecule junction.
AB  - The conductance of a single-molecule junction in a low-temperature scanning
      tunneling microscope has been measured at nanosecond time resolution. In a
      transition region between tunneling and contact the conductance exhibits rapid
      two-level fluctuations which are attributed to different geometries of the
      junction. The voltage dependence of the fluctuations indicates that electrons
      injected into the lowest unoccupied molecular orbital may efficiently couple to
      molecular vibrations.

PMID- 21854027
TI  - Unifying model for the electrokinetic and phase behavior of aqueous suspensions
      containing short and long amphiphiles.
AB  - Aqueous suspensions containing oppositely charged colloidal particles and
      amphiphilic molecules can form fluid dispersions, foams, and percolating gel
      networks, depending on the initial concentration of amphiphiles. While models
      have been proposed to explain the electrokinetic and flotation behavior of
      particles in the presence of long amphiphilic molecules, the effect of
      amphiphiles with less than six carbons in the hydrocarbon tail on the
      electrokinetic, rheological, and foaming behavior of aqueous suspensions remains
      unclear. Unlike conventional long amphiphiles (>=10 carbons), short amphiphiles
      do not exhibit increased adsorption on the particle surface when the number of
      carbons in the molecule tail is increased. On the basis of classical electrical
      double layer theory and the formerly proposed hemimicelle concept, we put forward
      a new predictive model that reconciles the adsorption and electrokinetic behavior
      of colloidal particles in the presence of long and short amphiphiles. By
      introducing in the classical Gouy-Chapman theory an energy term associated with
      hydrophobic interactions between the amphiphile hydrocarbon tails, we show that
      amphiphilic electrolytes lead to a stronger compression of the diffuse part of
      the electrical double layer in comparison to hydrophilic electrolytes. Scaling
      relationships derived from this model provide a quantitative description of the
      rich phase behavior of the investigated suspensions, correctly accounting for the
      effect of the alkyl chain length of short and long amphiphiles on the
      electrokinetics of such colloidal systems. The proposed model contributes to our
      understanding of the stabilization mechanisms of particle-stabilized foams and
      emulsions and might provide new insights into the physicochemical processes
      involved in mineral flotation.

PMID- 21854028
TI  - Perfectly alternating copolymerization of CO2 and epichlorohydrin using
      cobalt(III)-based catalyst systems.
AB  - Selective transformations of carbon dioxide and epoxides into biodegradable
      polycarbonates by the alternating copolymerization of the two monomers represent
      some of the most well-studied and innovative technologies for potential large
      scale utilization of carbon dioxide in chemical synthesis. For the most part,
      previous studies of these processes have focused on the use of aliphatic terminal
      epoxides or cyclohexene oxide derivatives, with only rare reports concerning the
      synthesis of CO(2) copolymers from epoxides containing electron-withdrawing
      groups such as styrene oxide. Herein we report the production of the CO(2)
      copolymer with more than 99% carbonate linkages from the coupling of CO(2) with
      epichlorohydrin, employing binary and bifunctional (salen)cobalt(III)-based
      catalyst systems. Comparative kinetic studies were performed via in situ infrared
      measurements as a function of temperature to assess the activation barriers for
      the production of cyclic carbonate versus copolymer involving two electronically
      different epoxides: epichlorohydrin and propylene oxide. The relative small
      activation energy difference between copolymer versus cyclic carbonate formation
      for the epichlorohydrin/CO(2) process (45.4 kJ/mol) accounts in part for the
      selective synthesis of copolymer to be more difficult in comparison with the
      propylene oxide/CO(2) case (53.5 kJ/mol). Direct observation of the propagating
      polymer-chain species from the binary (salen)CoX/MTBD (X = 2,4-dinitrophenoxide
      and MTBD = 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene) catalyst system by means
      of electrospray ionization mass spectrometry confirmed the perfectly alternating
      nature of the copolymerization process. This observation in combination with
      control experiments suggests possible intermediates involving MTBD in the
      CO(2)/epichlorohydrin copolymerization process.

PMID- 21854029
TI  - Simulation studies of protein folding/unfolding equilibrium under polar and
      nonpolar confinement.
AB  - We study the equilibrium folding/unfolding thermodynamics of a small globular
      miniprotein, the Trp cage, that is confined to the interior of a 2 nm radius
      fullerene ball. The interactions of the fullerene surface are changed from
      nonpolar to polar to mimic the interior of the GroEL/ES chaperonin that assists
      proteins to fold in vivo. We find that nonpolar confinement stabilizes the folded
      state of the protein due to the effects of volume reduction that destabilize the
      unfolded state and also due to interactions with the fullerene surface. For the
      Trp cage, polar confinement has a net destabilizing effect that results from the
      stabilizing confinement and the competitive exclusion effect that keeps the
      protein away from the surface hydration shell and stronger interactions between
      charged side chains in the protein and the polar surface that compete against the
      formation of an ion pair that stabilizes the protein folded state. We show that
      confinement effects due to volume reduction can be overcome by sequence-specific
      interactions of the protein side chains with the encapsulating surface. This
      study shows that there is a complex balance among many competing effects that
      determine the mechanism of GroEL chaperonin in enhancing the folding rate of
      polypeptide inside its cavity.

PMID- 21854031
TI  - Stereoselective 6-exo cyclization of amidyl radicals. An experimental and
      theoretical study.
AB  - Unsaturated primary amidyl radicals of Z-configurations underwent efficient chemo
      and stereoselective 6-exo cyclization reactions via chair-conformational
      transition states, leading to the predominant formations of 3,6-trans, 4,6-cis,
      or 5,6-trans substituted delta-lactams.

PMID- 21854030
TI  - Synthesis, transport and mechanism of a type I prodrug: L-carnitine ester of
      prednisolone.
AB  - Aerosol glucocorticoid medications have become more and more important in
      treating BA (bronchial asthma). Although these agents are dosed to directly
      target airway inflammation, adrenocortical suppression and other systematic
      effects are still seen. To tackle this problem in a novel way, two L-carnitine
      ester derivatives of prednisolone (as the model drug), namely, PDC and PDSC, were
      synthesized to increase the absorption of prednisolone across the human bronchial
      epithelial BEAS-2B cells by the organic cation/carnitine transporter OCTN2
      (SLC22A5) and then to slowly and intracellularly release prednisolone. The
      transport of prednisolone, PDC and PDSC into the human bronchial epithelial BEAS
      2B cells was in the order PDSC > prednisolone > PDC at 37  degrees C. It was
      found that PDSC displayed 1.79-fold increase of uptake compared to prednisolone.
      Transport of PDSC by BEAS-2B was temperature-, time-, and Na(+)-dependent and
      saturable, with an apparent K(m) value of 329.74 MUM, suggesting the involvement
      of carrier-mediated uptake. An RT-PCR study showed that organic cation/carnitine
      transporters OCTN1 and OCTN2 are expressed in BEAS-2B cells, but little in
      HEK293T cells. The order of uptake by HEK293T was prednisolone > PDC > PDSC. In
      addition, the inhibitory effects of organic cations such as L-carnitine,
      ergothioneine, TEA(+) and ipratropium on PDSC uptake in BEAS-2B cells were in the
      order L-carnitine > ipratropium > TEA(+) > ergothioneine, whereas their
      inhibitory effects on PDSC uptake in HEK293T cells were negligible. Finally, in
      vitro LPS-induced IL-6 production from BEAS-2B was more and longer suppressed by
      PDSC than prednisolone and PDC. All of these results suggested PDSC may be an
      attractive candidate for asthma treatment.

PMID- 21854032
TI  - Free-standing mesoporous carbon thin films with highly ordered pore architectures
      for nanodevices.
AB  - We report for the first time the synthesis of free-standing mesoporous carbon
      films with highly ordered pore architecture by a simple coating-etching approach,
      which have an intact morphology with variable sizes as large as several square
      centimeters and a controllable thickness of 90 nm to ~3 MUm. The mesoporous
      carbon films were first synthesized by coating a resol precursors/Pluronic
      copolymer solution on a preoxidized silicon wafer and forming highly ordered
      polymeric mesostructures based on organic-organic self-assembly, followed by
      carbonizing at 600  degrees C and finally etching of the native oxide layer
      between the carbon film and the silicon substrate. The mesostructure of this free
      standing carbon film is confirmed to be an ordered face-centered orthorhombic
      Fmmm structure, distorted from the (110) oriented body-centered cubic Im3m
      symmetry. The mesoporosity of the carbon films has been evaluated by nitrogen
      sorption, which shows a high specific BET surface area of 700 m(2)/g and large
      uniform mesopores of ~4.3 nm. Both mesostructures and pore sizes can be tuned by
      changing the block copolymer templates or the ratio of resol to template. These
      free-standing mesoporous carbon films with cracking-free uniform morphology can
      be transferred or bent on different surfaces, especially with the aid of the soft
      polymer layer transfer technique, thus allowing for a variety of potential
      applications in electrochemistry and biomolecule separation. As a proof of
      concept, an electrochemical supercapacitor device directly made by the mesoporous
      carbon thin films shows a capacitance of 136 F/g at 0.5 A/g. Moreover, a
      nanofilter based on the carbon films has shown an excellent size-selective
      filtration of cytochrome c and bovine serum albumin.

PMID- 21854033
TI  - Self-assembly properties and dynamics of synthetic proteo-nucleic building blocks
      in solution and on surfaces.
AB  - Synthetic proteo-nucleic structures (PDNAs) encompassing a single-stranded DNA
      sequence covalently attached to a redox protein domain able to interact with
      surface or matrix were designed and characterized. They constitute versatile
      building blocks alternative to regular DNA for creating scaffolds with optical,
      electrical, or catalytic properties. PDNAs self-assemble in the presence of
      complementary oligonucleotides, to form a network of protein domains linked by
      double-stranded DNA segments. Electrophoretic and hydrodynamic behaviors of PDNAs
      and corresponding DNA were compared under electrophoresis and gel filtration
      conditions. Hybridization rates between small and large assemblies were
      characterized by rapid-mixing experiments. Results showed that the protein part
      significantly contributes to hydrodynamic behaviors of structures but marginally
      affects the conformation and hybridization properties of the nucleic domain. PDNA
      metal-mediated complexes with nitriloacetate-modified phospholipids can diffuse
      and interact at the surface of vesicles or supported membranes. Surface plasmon
      resonance analysis of membrane-PDNA interactions indicated that two protein units
      are required to allow stable surface association and that surface occupancy
      constrains assembly sizes. High-speed atomic force microscopy illustrated rapid
      lateral diffusion of assemblies on mica, revealing transient association between
      noncomplementary PDNA extremities and frequent trapping by surface defects.
      Regularly organized protein domains were visualized using a larger DNA framework.

PMID- 21854034
TI  - Efficient ternary blend bulk heterojunction solar cells with tunable open-circuit
      voltage.
AB  - To explore the potential of ternary blend bulk heterojunction (BHJ) photovoltaics
      as a general platform for increasing the attainable performance of organic solar
      cells, a model system based on poly(3-hexylthiophene) (P3HT) as the donor and two
      soluble fullerene acceptors, phenyl-C(61)-butyric acid methyl ester (PC(61)BM)
      and indene-C(60) bisadduct (ICBA), was examined. In all of the solar cells, the
      overall ratio of polymer to fullerene was maintained at 1:1, while the
      composition of the fullerene component (PC(61)BM:ICBA ratio) was varied.
      Photovoltaic devices showed high short-circuit current densities (J(sc)) and fill
      factors (FF) (>0.57) at all fullerene ratios, while the open-circuit voltage
      (V(oc)) was found to vary from 0.61 to 0.84 V as the fraction of ICBA was
      increased. These results indicate that the V(oc) in ternary blend BHJ solar cells
      is not limited to the smallest V(oc) of the corresponding binary blend solar
      cells but can be varied between the extreme V(oc) values without significant
      effect on the J(sc) or FF. By extension, this result suggests that ternary blends
      provide a potentially effective route toward maximizing the attainable J(sc)V(oc)
      product (which is directly proportional to the solar cell efficiency) in BHJ
      solar cells and that with judicious selection of donor and acceptor components,
      solar cells with efficiencies exceeding the theoretical limits for binary blend
      solar cells could be possible without sacrificing the simplicity of a single
      active-layer processing step.

PMID- 21854035
TI  - Acid--chlorite pretreatment and liquefaction of cornstalk in hot-compressed water
      for bio-oil production.
AB  - In this study, cornstalk was pretreated by an acid-chlorite delignification
      procedure to enhance the conversion of cornstalk to bio-oil in hot-compressed
      water liquefaction. The effects of the pretreatment conditions on the
      compositional and structural changes of the cornstalk and bio-oil yield were
      investigated. It was found that acid-chlorite pretreatment changed the main
      components and physical structures of cornstalk and effectively enhanced the bio
      oil yield. Shorter residence time favored production of the total bio-oil
      products, whereas longer time led to cracking of the products. A high water
      loading was found to be favorable for high yields of total bio-oil and water
      soluble oil. GC-MS analysis showed that the water-soluble oil and heavy oil were
      the complicated products of C(5-10) and C(8-11) organic compounds.

PMID- 21854036
TI  - A binary ant colony optimization classifier for molecular activities.
AB  - Chemical fingerprints encode the presence or absence of molecular features and
      are available in many large databases. Using a variation of the Ant Colony
      Optimization (ACO) paradigm, we describe a binary classifier based on feature
      selection from fingerprints. We discuss the algorithm and possible cross
      validation procedures. As a real-world example, we use our algorithm to analyze a
      Plasmodium falciparum inhibition assay and contrast its performance with other
      machine learning paradigms in use today (decision tree induction, random forests,
      support vector machines, artificial neural networks). Our algorithm matches
      established paradigms in predictive power, yet supplies the medicinal chemist and
      basic researcher with easily interpretable results. Furthermore, models generated
      with our paradigm are easy to implement and can complement virtual screenings by
      additionally exploiting the precalculated fingerprint information.

PMID- 21854037
TI  - Subarctic weathering of mineral wastes provides a sink for atmospheric CO(2).
AB  - The mineral waste from some mines has the capacity to trap and store CO(2) within
      secondary carbonate minerals via the process of silicate weathering. Nesquehonite
      [MgCO(3).3H(2)O] forms by weathering of Mg-silicate minerals in kimberlitic mine
      tailings at the Diavik Diamond Mine, Northwest Territories, Canada. Less abundant
      Na- and Ca-carbonate minerals precipitate from sewage treatment effluent
      deposited in the tailings storage facility. Radiocarbon and stable carbon and
      oxygen isotopes are used to assess the ability of mine tailings to trap and store
      modern CO(2) within these minerals in the arid, subarctic climate at Diavik.
      Stable isotopic data cannot always uniquely identify the source of carbon stored
      within minerals in this setting; however, radiocarbon isotopic data provide a
      reliable quantitative estimate for sequestration of modern carbon. At least 89%
      of the carbon trapped within secondary carbonate minerals at Diavik is derived
      from a modern source, either by direct uptake of atmospheric CO(2) or indirect
      uptake though the biosphere. Silicate weathering at Diavik is trapping 102-114 g
      C/m(2)/y within nesquehonite, which corresponds to a 2 orders of magnitude
      increase over the background rate of CO(2) uptake predicted from arctic and
      subarctic river catchment data.

PMID- 21854039
TI  - Modulation of electronic couplings within Ru2-polyyne frameworks.
AB  - Dimers of [Ru(2)(Xap)(4)] bridged by 1,3,5-hexatriyn-diyl (Xap are 2
      anilinopyridinate and its aniline substituted derivatives), [Ru(2)(Xap)(4)](2)(MU
      C(6)) (1), were prepared. Compounds 1 reacted with 1 equiv of tetracyanoethene
      (TCNE) to yield the cyclo-addition/insertion products [Ru(2)(Xap)(4)](2){MU
      C=CC(C(CN)(2))-C(C(CN)(2))C=C} (2) and 1 equiv of Co(2)(dppm)(CO)(6) to yield the
      eta(2)-Co(2) adducts to the middle C=C bond, [Ru(2)(Xap)(4)](2)(MU
      C(6))(Co(2)(dppm)(CO)(4)) (3). Voltammetric and spectroelectrochemical studies
      revealed that (i) two Ru(2) termini in 1 are sufficiently coupled with the
      monoanion (1(-)) as a Robin-Day class II/III mixed valence species; (ii) the
      coupling between two Ru(2) is still significant but somewhat weakened in 3; and
      (iii) the coupling between two Ru(2) is completely removed by the insertion of
      TCNE in 2. The attenuation of electronic couplings in 2 and 3 was further
      explored with both the X-ray diffraction study of representative compounds and
      spin-unrestricted DFT calculations.

PMID- 21854038
TI  - Photothermal imaging and measurement of protein shell stoichiometry of single HIV
      1 Gag virus-like nanoparticles.
AB  - Virus life stages often constitute a complex chain of events, difficult to track
      in vivo and in real-time. Challenges are associated with spatial and time
      limitations of current probes: most viruses are smaller than the diffraction
      limit of optical microscopes while the entire time scale of virus dynamics spans
      over 8 orders of magnitude. Thus, virus processes such as entry, disassembly, and
      egress have generally remained poorly understood. Here we discuss photothermal
      heterodyne imaging (PHI) as a possible alternative to fluorescence microscopy in
      the study of single virus-like nanoparticle (VNP) dynamics, with relevance in
      particular to virus uncoating. Being based on optical absorption rather than
      emission, PHI could potentially surpass some of the current limitations
      associated with fluorescent labels. As proof-of-principle, single VNPs self
      assembled from 60 nm DNA-functionalized gold nanoparticles (DNA-Au NPs)
      encapsulated in a Gag protein shell of the human immunodeficiency virus (HIV-1)
      were imaged, and their photothermal response was compared with DNA-Au NPs. For
      the first time, the protein stoichiometry of a single virus-like particle was
      estimated by a method other than electron microscopy.

PMID- 21854040
TI  - New insights into an ancient antibrowning agent: formation of sulfophenolics in
      sodium hydrogen sulfite-treated potato extracts.
AB  - The effect of sodium hydrogen sulfite (S), used as antibrowning agent, on the
      phenolic profile of potato extracts was investigated. This extract was compared
      to one obtained in the presence of ascorbic acid (A). In the presence of A, two
      major compounds were obtained, 5-O-caffeoylquinic acid (5-CQA) and 4-O-caffeoyl
      quinic acid. With S, their 2'-sulfo-adducts were found instead, the structures of
      which were confirmed by nuclear magnetic resonance spectroscopy and mass
      spectrometry. Also, for minor caffeoyl derivatives and quercetin glycosides, the
      corresponding sulfo-adducts were observed. Feruloyl and sinapoyl derivatives were
      not chemically affected by the presence of S. Polyphenol oxidase (PPO) was
      thought to be responsible for the formation of the sulfo-adducts. This was
      confirmed by preparing 2'-sulfo-5-O-caffeoyl quinic acid in a model system using
      5-CQA, sodium hydrogen sulfite, and PPO. This sulfo-adduct exhibited a small
      bathochromic shift (lambdamax 329 nm) as compared to 5-CQA (lambdamax 325 nm) and
      a strong hypochromic shift with an extinction coefficient of 9357+/-395 M(-1) cm(
      1) as compared to 18494+/-196 M(-1) cm(-1), respectively. The results suggest
      that whenever S is used as an antibrowning agent, the O-quinone formed with PPO
      reacts with S to produce sulfo-O-diphenol, which does not participate in browning
      reactions.

PMID- 21854041
TI  - A sulfone-based strategy for the preparation of 2,4-disubstituted furan
      derivatives.
AB  - 2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1
      propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming
      step involves a deacetylation, and the selectivity of this process depends upon
      the steric demand of the R group. The substituent in position 4 is elaborated by
      reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes.
      Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in
      60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the
      naturally occurring nematotoxic furoic acid 13.

PMID- 21854042
TI  - Alkynylation of benzotriazole with silylethynyliodonium triflates. Regioselective
      synthesis of 2-ethynyl-2H-benzotriazole derivatives.
AB  - Phenyl(trimethylsilylethynyl)iodonium and tert
      butyldimethylsilylethynyl(phenyl)iodonium triflates were applied to alkynylation
      of benzotriazole. Treatment of the silylethynyliodonium triflates with the
      potassium salt of benzotriazole ion in (t)BuOH and CH(2)Cl(2) gave 2
      (trimethylsilylethynyl)-2H-1,2,3-benzotriazole and 2-(tert
      butyldimethylsilylethynyl)-2H-1,2,3-benzotriazole in 74% and 76% yields,
      respectively. The regioisomers, 1-silylethynyl-1H-1,2,3-benzotriazole
      derivatives, were minor. In both cases of the silyl-substitued ethynyliodonium
      salts, novel regioselective alkynylation of benzotriazole at the 2 position was
      observed.

PMID- 21854045
TI  - Spectroscopy of the free phenalenyl radical.
AB  - After benzene and naphthalene, the smallest polycyclic aromatic hydrocarbon
      bearing six-membered rings is the threefold-symmetric phenalenyl radical. Despite
      the fact that it is so fundamental, its electronic spectroscopy has not been
      rigorously scrutinized, in spite of growing interest in graphene fragments for
      molecular electronic applications. Here we used complementary laser spectroscopic
      techniques to probe the jet-cooled phenalenyl radical in vacuo. Its spectrum
      reveals the interplay between four electronic states that exhibit Jahn-Teller and
      pseudo-Jahn-Teller vibronic coupling. The coupling mechanism has been elucidated
      by the application of various ab initio quantum-chemical techniques.

PMID- 21854044
TI  - Influence of grape-harvesting steps on varietal thiol aromas in Sauvignon blanc
      wines.
AB  - The intense tropical fruit aroma of Sauvignon blanc wines has been associated
      with the varietal thiols 3-mercaptohexanol (3MH), derived from odorless
      precursors in the grape, and 3-mercaptohexyl acetate (3MHA), arising from 3MH
      during fermentation. Grapes and juice were sourced from five locations in
      Marlborough, New Zealand, taking hand-picked grapes and samples at four stages
      during the mechanical harvesting process and pressing, which were then fermented
      in replicated 750 mL bottles. With each set of juices, the highest concentrations
      of Cys-3MH and Glut-3MH were found in the juices pressed to 1 bar, but these
      juices produced wines with lower 3MH and 3MHA concentrations. With three of the
      juices, there was an increase in varietal thiol content for wines made from
      juices that had been machine harvested compared to the hand-picked samples, which
      matched earlier findings of lower 3MH and 3MHA levels in wines made from hand
      picked grapes. Juices that were more oxidized, and which showed a higher
      absorbance at 420 nm, were found to produce wines with lower 3MH and 3MHA
      concentrations.

PMID- 21854046
TI  - Sources of conductivity and doping limits in CdO from hybrid density functional
      theory.
AB  - CdO has been studied for decades as a prototypical wide band gap transparent
      conducting oxide with excellent n-type ability. Despite this, uncertainty remains
      over the source of conductivity in CdO and over the lack of p-type CdO, despite
      its valence band maximum (VBM) being high with respect to other wide band gap
      oxides. In this article, we use screened hybrid DFT to study intrinsic defects
      and hydrogen impurities in CdO and identify for the first time the source of
      charge carriers in this system. We explain why the oxygen vacancy in CdO acts as
      a shallow donor and does not display negative-U behavior similar to all other
      wide band gap n-type oxides. We also demonstrate that p-type CdO is not
      achievable, as n-type defects dominate under all growth conditions. Lastly, we
      estimate theoretical doping limits and explain why CdO can be made transparent by
      a large Moss-Burstein shift caused by suitable n-type doping.

PMID- 21854047
TI  - Silica nanorattle-doxorubicin-anchored mesenchymal stem cells for tumor-tropic
      therapy.
AB  - Low targeting efficiency is one of the biggest limitations for nanoparticulate
      drug delivery system-based cancer therapy. In this study, an efficient approach
      for tumor-targeted drug delivery was developed with mesenchymal stem cells as the
      targeting vehicle and a silica nanorattle as the drug carrier. A silica
      nanorattle-doxorubicin drug delivery system was efficiently anchored to
      mesenchymal stem cells (MSCs) by specific antibody-antigen recognitions at the
      cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles
      were uploaded to each MSC cell with high cell viability and tumor-tropic ability.
      The intracellular retention time of the silica nanorattle was no less than 48 h,
      which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments
      proved that the burdened MSCs can track down the U251 glioma tumor cells more
      efficiently and deliver doxorubicin with wider distribution and longer retention
      lifetime in tumor tissues compared with free DOX and silica nanorattle
      encapsulated DOX. The increased and prolonged DOX intratumoral distribution
      further contributed to significantly enhanced tumor-cell apoptosis. This strategy
      has potential to be developed as a robust and generalizable method for targeted
      tumor therapy with high efficiency and low systematic toxicity.

PMID- 21854048
TI  - Mechanism of formation of the internal aldimine in pyridoxal 5'-phosphate
      dependent enzymes.
AB  - In this paper we studied the mechanism of formation of the internal aldimine, a
      common intermediate to most pyridoxal 5'-phosphate (PLP)-dependent enzymes. A
      large model based on the crystal structure from the human ornithine decarboxylase
      (ODC) enzyme was constructed and in total accounts for 504 atoms. The reaction
      mechanism was investigated using the ONIOM methodology (B3LYP/6-31G(d)//AM1), and
      the final energies were calculated with the M06/6-311++G(2d,2p)//B3LYP/6-31G(d)
      level of theory. It was demonstrated that the reaction is accomplished in three
      sequential steps: (i) the nucleophilic attack of Lysine69 to PLP, (ii) the
      carbinolamine formation, and (iii) a final dehydration step. For the
      carbinolamine formation, several mechanistic hypotheses were explored, and the
      preferred pathway assigns a key role for the conserved active site Cys360. The
      overall reaction is exergonic in -9.1 kcal/mol, and the rate-limiting step is the
      dehydration step (E(a) = 13.5 kcal/mol). For the first time, we provide an
      atomistic portrait of this mechanism in an enzymatic environment. Moreover, we
      were able to assign a novel role to Cys360 in the ODC reaction mechanism that was
      never proposed.

PMID- 21854049
TI  - Synthesis and characterization of SIRT6 protein coated magnetic beads:
      identification of a novel inhibitor of SIRT6 deacetylase from medicinal plant
      extracts.
AB  - SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic
      target for metabolic disorders and the prevention of age-associated diseases.
      Thus, the identification of compounds that modulate SIRT6 activity could be of
      great therapeutic importance. The aim of this study was to develop a screening
      method for the identification of novel modulators of SIRT6 from a natural plant
      extract. We immobilized SIRT6 onto the surface of magnetic beads, and assessed
      SIRT6 enzymatic activity on synthetic acetylated histone tails (H3K9Ac) by
      measuring products of the deacetylation process. The SIRT6 coated magnetic beads
      were then suspended in fenugreek seed extract (Trigonella foenum-graecum) as a
      bait to identify active ligands that suppress SIRT6 activity. While the entire
      extract also inhibited SIRT6 activity in a cell-based assay, the inhibitory
      effect of two flavonoids from this extract, quercetin and vitexin, was only
      detected in vitro. This is the first report on the use of protein-coated magnetic
      beads for the identification of an active ligand from a botanical matrix, and it
      sets the basis for the de novo identification of SIRT6 modulators from complex
      biological mixtures.

PMID- 21854050
TI  - Highly sensitive pyrosequencing system with polymer-supported enzymes for high
      throughput DNA analysis.
AB  - A highly sensitive massively parallel pyrosequencing system employing a gel
      matrix to immobilize enzymes at high density in microreaction chambers is
      demonstrated. Reducing the size of microreaction chambers in a DNA analyzer is
      important to achieve a high throughput utilizing a commercially available
      detection device or camera. A high-performance system can be attained by
      detecting signals from one reaction chamber with one photopixel of around several
      micrometers by utilizing a 1:1 image magnification. However, the use of small
      beads immobilizing DNA has a disadvantage in detecting luminescence because only
      small amounts of DNA can be immobilized on the bead surfaces for sequencing. As
      luminescence intensity could be enhanced by increasing the luciferase density in
      the chambers, we overcame this difficulty by using a gel matrix to immobilize
      luciferase at a high concentration in the microreaction chambers. Luminescence 1
      order of magnitude higher could be observed with the new method compared to the
      conventional method. Consequently, the chamber size and bead size immobilizing
      DNA could be reduced to as small as 6.5 and 4 MUm, respectively. This can be
      successfully applied to achieving small, inexpensive, pyrosequencing systems with
      high throughput.

PMID- 21854051
TI  - Continuous-flow biomolecule and cell concentrator by ion concentration
      polarization.
AB  - We present a novel continuous-flow nanofluidic biomolecule/cell concentrator,
      utilizing the ion concentration polarization (ICP) phenomenon. The device has one
      main microchannel which bifurcates into two channels, one for a narrow,
      concentrated stream and the other for a wider but target-free stream. A
      nanojunction [cation-selective material (Nafion)] is patterned along the tilted
      concentrated channel. Application of an electric field generates the ICP zone
      near the nanojunction so that biomolecules and cells are guided into the narrow,
      concentrated channel by hydrodynamic force. Once biomolecules from the main
      channel are continuously streamed out to the concentrated channel, one can
      achieve a continuous flow of the same sample solution but with higher
      concentrations up to 100-fold. By controlling hydrodynamic resistance of the main
      and concentrated channel, the concentration factors can be adjusted. We
      demonstrated the continuous-flow concentration with various targets, such as
      bacteria [fluorescein sodium salt, recombinant green fluorescence protein (rGFP),
      red blood cells (RBCs), and  Escherichia coli  ( E. coli )]. Specially,
      fluorescein isothiocyanate (FITC)-conjugated lectin from  Lens culinaris 
      (lentil) (FITC-lectin) was tested on the different buffer conditions to clarify
      the effect of polarities of the target sample. This system is ideally suited for
      a generic concentration front-end for a wide variety of biosensors, with minimal
      integration-related complications.

PMID- 21854052
TI  - Distribution of fullerene nanomaterials between water and model biological
      membranes.
AB  - Biological membranes are one of the important interfaces between cells and
      pollutants. Many polar and hydrophobic chemicals can accumulate within these
      membranes. For this reason, artificial biological membranes are appealing
      surrogates to complex organisms for assessing the bioaccumulation potential of
      engineered nanomaterials (ENMs). To our knowledge, this work presents the first
      quantitative study on the distribution of fullerene ENMs between lipid bilayers,
      used as model biological membranes, and water. We evaluated the lipid bilayer
      water association coefficients (K(lipw)) of aqueous fullerene aggregates (nC(60))
      and fullerol (C(60)(ONa)(x)(OH)(y), x + y = 24). Kinetic studies indicated that
      fullerol reached apparent equilibrium more rapidly than nC(60) (2 h versus >9 h).
      Nonlinear isotherms can describe the distribution behavior of nC(60) and
      fullerol. The lipid bilayer-water distributions of both nC(60) and fullerol were
      pH-dependent with the accumulation in lipid bilayers increasing systematically as
      the pH decreased from 8.6 (natural water pH) to 3 (the low end of physiologically
      relevant pH). This pH dependency varies with the zeta potentials of the ENMs and
      leads to patterns similar to those previously observed for the lipid bilayer
      water distribution behavior of ionizable organic pollutants. The K(lipw) value
      for nC(60) was larger than that of fullerol at a given pH, indicating a greater
      propensity for nC(60) to interact with lipid bilayers. For example, at pH 7.4 and
      an aqueous concentration of 10 mg/L, K(lipw) was 3.5 times greater for nC(60)
      (log K(lipw) = 2.99) relative to fullerol (log K(lipw) = 2.45). Comparisons with
      existing aquatic organism bioaccumulation studies suggested that the lipid
      bilayer-water distribution is a potential method for assessing the
      bioaccumulation potentials of ENMs.

PMID- 21854053
TI  - Anatomy of high-performance 2D similarity calculations.
AB  - Similarity measures based on the comparison of dense bit vectors of two
      dimensional chemical features are a dominant method in chemical informatics. For
      large-scale problems, including compound selection and machine learning,
      computing the intersection between two dense bit vectors is the overwhelming
      bottleneck. We describe efficient implementations of this primitive as well as
      example applications using features of modern CPUs that allow 20-40* performance
      increases relative to typical code. Specifically, we describe fast methods for
      population count on modern x86 processors and cache-efficient matrix traversal
      and leader clustering algorithms that alleviate memory bandwidth bottlenecks in
      similarity matrix construction and clustering. The speed of our 2D comparison
      primitives is within a small factor of that obtained on GPUs and does not require
      specialized hardware.

PMID- 21854054
TI  - Conjugated linoleic acid regulates phosphorylation of PPARgamma by modulation of
      ERK 1/2 and p38 signaling in human macrophages/fatty acid-laden macrophages.
AB  - Stimulation of macrophages by a variety fatty acids causes activation of MAP
      kinases (MAPKs). The consequences arising from down-regulation of MAPKs may be a
      limitation in the activity of PPARgamma, which is modulated by a modification
      catalyzed by these kinases. Phosphorylation of MAP kinases-ERK1/2 and p38 as well
      as PPARgamma was determined by real-time polymerase chain reaction and Western
      blotting in human macrophages cultured with conjugated linoleic acids (CLAs). We
      demonstrated that CLA isomers alter MAP kinase phosphorylation and PPARgamma
      activation. Phosphorylation of ERK1/2 was diminished in cells cultivated with cis
      9,trans-11 CLA, whereas phosphorylation of p38 was reduced by trans-10,cis-12
      CLA. PPARgamma was phosphorylated mainly by ERK1/2, and consequently, PPARgamma
      phosphorylation was suppressed mainly by cis-9,trans-11 isomer. In human
      adipocytes, cis-9,trans-11 C 18:2 raised the activation of PPAR and several of
      its downstream target genes. We suggest that a similar process may also occur in
      human macrophages.

PMID- 21854055
TI  - Characterization of codon-optimized recombinant candida rugosa lipase 5 (LIP5).
AB  - Recombinant Candida rugosa lipase 5 (LIP5) has been functionally expressed along
      with other isoforms in our laboratory. However, the characterization and codon
      optimization of LIP5 have not been done. In this work, we characterized, codon
      optimized and compared LIP5 with commercial lipase. LIP5 activity on hydrolysis
      of p-nitrophenyl (p-NP) butyrate was optimal at 55  degrees C as compared with 37
      degrees C of the commercial lipase. Several assays were also performed to
      determine the substrate specificity of LIP5. p-NP butyrate (C(4)), butyryl-CoA
      (C(4)), cholesteryl laurate (C(12)), and N-carbobenzoxy-l-tyrosine-p-nitrophenyl
      ester (l-NBTNPE) were found as preferred substrates of LIP5. Interestingly, LIP5
      specificity on hydrolysis of amino acid-derivative substrates was shown to be the
      highest among any lipase isoforms, but it had very weak preference on hydrolyzing
      triacylglycerol substrates. LIP5 also displays a pH-dependent maximum activity of
      a lipase but an esterase substrate preference in general. The characterization of
      LIP5 along with that of LIP1-LIP4 previously identified shows that each lipase
      isoform has a distinct substrate preference and catalytic activity.

PMID- 21854057
TI  - Monodisperse hexagonal silver nanoprisms: synthesis via thiolate-protected
      cluster precursors and chiral, ligand-imprinted self-assembly.
AB  - Silver nanoprisms of a predominantly hexagonal shape have been prepared using a
      ligand combination of a strongly binding thiol, captopril, and charge-stabilizing
      citrate together with hydrogen peroxide as an oxidative etching agent and a
      strong base that triggered nanoprism formation. The role of the reagents and
      their interplay in the nanoprism synthesis is discussed in detail. The beneficial
      role of chloride ions to attain a high degree of reproducibility and
      monodispersity of the nanoprisms is elucidated. Control over the nanoprism width,
      thickness, and, consequently, plasmon resonance in the system has been
      demonstrated. One of the crucial factors in the nanoprism synthesis was the slow,
      controlled aggregation of thiolate-stabilized silver nanoclusters as the
      intermediates. The resulting superior monodispersity (better than ca. 10%
      standard deviation in lateral size and ca. 15% standard deviation in thickness
      (<1 nm variation)) and charge stabilization of the produced silver nanoprisms
      enabled the exploration of the rich diversity of the self-assembled morphologies
      in the system. Regular columnar assemblies of the self-assembled nanoprisms
      spanning 2-3 MUm in length have been observed. Notably, the helicity of the
      columnar phases was evident, which can be attributed to the chirality of the
      strongly binding thiol ligand. Finally, the enhancement of Raman scattering has
      been observed after oxidative removal of thiolate ligands from the AgNPR surface.

PMID- 21854056
TI  - Graphene flash memory.
AB  - Graphene's single atomic layer of sp(2) carbon has recently garnered much
      attention for its potential use in electronic applications. Here, we report a
      memory application for graphene, which we call graphene flash memory (GFM). GFM
      has the potential to exceed the performance of current flash memory technology by
      utilizing the intrinsic properties of graphene, such as high density of states,
      high work function, and low dimensionality. To this end, we have grown large-area
      graphene sheets by chemical vapor deposition and integrated them into a floating
      gate structure. GFM displays a wide memory window of ~6 V at significantly low
      program/erase voltages of +/-7 V. GFM also shows a long retention time of more
      than 10 years at room temperature. Additionally, simulations suggest that GFM
      suffers very little from cell-to-cell interference, potentially enabling scaling
      down far beyond current state-of-the-art flash memory devices.

PMID- 21854059
TI  - Networks of ultrasmall Pd/Cr nanowires as high performance hydrogen sensors.
AB  - The newly developed hydrogen sensor, based on a network of ultrasmall pure
      palladium nanowires sputter-deposited on a filtration membrane, takes advantage
      of single palladium nanowires' characteristics of high speed and sensitivity
      while eliminating their nanofabrication obstacles. However, this new type of
      sensor, like the single palladium nanowires, cannot distinguish hydrogen
      concentrations above 3%, thus limiting the potential applications of the sensor.
      This study reports hydrogen sensors based on a network of ultrasmall Cr-buffered
      Pd (Pd/Cr) nanowires on a filtration membrane. These sensors not only are able to
      outperform their pure Pd counterparts in speed and durability but also allow
      hydrogen detection at concentrations up to 100%. The new networks consist of a
      thin layer of palladium deposited on top of a Cr adhesion layer 1-3 nm thick.
      Although the Cr layer is insensitive to hydrogen, it enables the formation of a
      network of continuous Pd/Cr nanowires with thicknesses of the Pd layer as thin as
      2 nm. The improved performance of the Pd/Cr sensors can be attributed to the
      increased surface area to volume ratio and to the confinement-induced suppression
      of the phase transition from Pd/H solid solution (alpha-phase) to Pd hydride
      (beta-phase).

PMID- 21854058
TI  - Synthesis of phosphine and antibody-azide probes for in vivo Staudinger ligation
      in a pretargeted imaging and therapy approach.
AB  - The application of intact monoclonal antibodies (mAbs) as targeting agents in
      nuclear imaging and radioimmunotherapy is hampered by the slow pharmacokinetics
      of these molecules. Pretargeting with mAbs could be beneficial to reduce the
      radiation burden to the patient, while using the excellent targeting capacity of
      the mAbs. In this study, we evaluated the applicability of the Staudinger
      ligation as pretargeting strategy using an antibody-azide conjugate as tumor
      targeting molecule in combination with a small phosphine-containing
      imaging/therapeutic probe. Up to 8 triazide molecules were attached to the
      antibody without seriously affecting its immunoreactivity, pharmacokinetics, and
      tumor uptake in tumor bearing nude mice. In addition, two (89)Zr- and (67/68)Ga
      labeled desferrioxamine (DFO)-phosphines, a (177)Lu-1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-phosphine and a (123)I
      cubyl phosphine probe were synthesized and characterized for their
      pharmacokinetic behavior in nude mice. With respect to the phosphine probes,
      blood levels at 30 min after injection were <5% injected dose per gram tissue,
      indicating rapid blood clearance. In vitro Staudinger ligation of 3.33 MUM
      antibody-azide conjugate with 1 equiv of radiolabeled phosphine, relative to the
      azide, in aqueous solution resulted in 20-25% efficiency after 2 h. The presence
      of 37% human serum resulted in a reduced ligation efficiency (reduction max. 30%
      at 2 h), while the phosphines were still >80% intact. No in vivo Staudinger
      ligation was observed in a mouse model after injection of 500 MUg antibody-azide,
      followed by 68 MUg DFO-phosphine at t = 2 h, and evaluation in blood at t = 7 h.
      To explain negative results in mice, Staudinger ligation was performed in vitro
      in mouse serum. Under these conditions, a side product with the phosphine was
      formed and ligation efficiency was severely reduced. It is concluded that in vivo
      application of the Staudinger ligation in a pretargeting approach in mice is not
      feasible, since this ligation reaction is not bioorthogonal and efficient enough.
      Slow reaction kinetics will also severely restrict the applicability of
      Staudinger ligation in humans.

PMID- 21854060
TI  - Mass spectrometric detection of targeting peptide bioconjugation to Red clover
      necrotic mosaic virus.
AB  - Plant virus nanoparticle (PVN) formulations constructed from Red clover necrotic
      mosaic virus by drug infusion and targeting peptide conjugation can be employed
      as drug delivery tools. In this investigation, we studied the cross-linked
      structures formed by application of sulfosuccinimidyl-4-(N-maleimidomethyl)
      cyclohexane-1-carboxylate (sSMCC) and succinimidyl-[(N-maleimidopropionamido)
      hexaethylene glycol] ester (SMPEG) as heterobifunctional linkers in the
      bioconjugation process. The plant virus formulations using several targeting
      peptides cross-linked to the plant virus capsid were characterized by LC/MS(E)
      analysis, which produced at least 69% sequence coverage using trypsin and
      chymotrypsin digestion. The results showed evidence for several types of
      modification located in three domains of the capsid protein. Extensive linker
      modifications on lysines or cysteines were detected in all the domains, including
      both intended peptide-capsid cross-links and unintended intracapsid cross-links.
      Surprisingly, the most extensive peptide modification was observed in the R
      domain, which is thought to be quite inaccessible to peptides and cross-linking
      reagents in solution, since it is on the interior of the virus. These results
      show that heterobifunctional linkers may not be the most efficient method for
      attachment of peptides to plant virus capsids. As an alternative conjugation
      strategy, maleimide peptides were used to conjugate with the virus in a one-step
      reaction. Analysis by LC/MS(E) showed that these one-step maleimide coupling
      reactions were more specific, such as modifications of C154 and to a lesser
      extent C267, and provide a means for achieving more effective PVN formulations.

PMID- 21854061
TI  - Novel royal jelly proteins identified by gel-based and gel-free proteomics.
AB  - Royal jelly (RJ) plays an important role in caste determination of the honeybee;
      the genetically same female egg develops into either a queen or worker bee
      depending on the time and amount of RJ fed to the larvae. RJ also has numerous
      health-promoting properties for humans. Gel-based and gel-free proteomics
      approaches and high-performance liquid chromatography-chip quadruple time-of
      flight tandem mass spectrometry were applied to comprehensively investigate the
      protein components of RJ. Overall, 37 and 22 nonredundant proteins were
      identified by one-dimensional gel electrophoresis and gel-free analysis,
      respectively, and 19 new proteins were found by these two proteomics approaches.
      Major royal jelly proteins (MRJPs) were identified as the principal protein
      components of RJ, and proteins related to carbohydrate metabolism such as glucose
      oxidase, alpha-glucosidase precursor, and glucose dehydrogenase were also
      successfully identified. Importantly, the 19 newly identified proteins were
      mainly classified into three functional categories: oxidation-reduction (ergic53
      CG6822-PA isoform A isoform 1, Sec61 CG9539-PA, and ADP/ATP translocase), protein
      binding (regucalcin and translationally controlled tumor protein CG4800-PA
      isoform 1), and lipid transport (apolipophorin-III-like protein). These new
      findings not only significantly increase the RJ proteome coverage but also help
      to provide new knowledge of RJ for honeybee biology and potential use for human
      health promotion.

PMID- 21854062
TI  - Interlevel cascade transition in electrically confined quantum wire arrays.
AB  - Vertical stacks of electrically confined quantum wires were demonstrated in
      devices with large areas. Multiple current plateaus and strong differential
      conductance oscillations were observed at above liquid nitrogen temperatures
      because of interlevel cascade transition of carriers. Our simulation results for
      charge transport, as well as interlevel infrared photoresponse red-shift, due to
      lateral electric field confinement show good agreement with experimental data.

PMID- 21854063
TI  - Chemical shifts for the unusual DNA structure in Pf1 bacteriophage from dynamic
      nuclear-polarization-enhanced solid-state NMR spectroscopy.
AB  - Solid-state NMR spectra, including dynamic nuclear polarization enhanced 400 MHz
      spectra acquired at 100 K, as well as non-DNP spectra at a variety of field
      strengths and at temperatures in the range 213-243 K, have allowed the assignment
      of the (13)C and (15)N resonances of the unusual DNA structure in the Pf1 virion.
      The (13)C chemical shifts of C3' and C5', considered to be key reporters of
      deoxyribose conformation, fall near or beyond the edges of their respective
      ranges in available databases. The (13)C and (15)N chemical shifts of the DNA
      bases have above-average values for AC4, AC5, CC5, TC2, and TC5, and below
      average values for AC8, GC8, and GN2, pointing to an absence of Watson-Crick
      hydrogen bonding, yet the presence of some type of aromatic ring interaction.
      Crosspeaks between Tyr40 of the coat protein and several DNA atoms suggest that
      Tyr40 is involved in this ring interaction. In addition, these crosspeak
      resonances and several deoxyribose resonances are multiply split, presumably
      through the effects of ordered but differing interactions between capsid protein
      subunits and each type of nucleotide in each of the two DNA strands. Overall,
      these observations characterize and support the DNA model proposed by Liu and Day
      and refined by Tsuboi et al., which calls for the most highly stretched and
      twisted naturally occurring DNA yet encountered.

PMID- 21854065
TI  - Aqueous dispersion polymerization: a new paradigm for in situ block copolymer
      self-assembly in concentrated solution.
AB  - Reversible addition-fragmentation chain transfer polymerization has been utilized
      to polymerize 2-hydroxypropyl methacrylate (HPMA) using a water-soluble
      macromolecular chain transfer agent based on poly(2
      (methacryloyloxy)ethylphosphorylcholine) (PMPC). A detailed phase diagram has
      been elucidated for this aqueous dispersion polymerization formulation that
      reliably predicts the precise block compositions associated with well-defined
      particle morphologies (i.e., pure phases). Unlike the ad hoc approaches described
      in the literature, this strategy enables the facile, efficient, and reproducible
      preparation of diblock copolymer spheres, worms, or vesicles directly in
      concentrated aqueous solution. Chain extension of the highly hydrated
      zwitterionic PMPC block with HPMA in water at 70  degrees C produces a
      hydrophobic poly(2-hydroxypropyl methacrylate) (PHPMA) block, which drives in
      situ self-assembly to form well-defined diblock copolymer spheres, worms, or
      vesicles. The final particle morphology obtained at full monomer conversion is
      dictated by (i) the target degree of polymerization of the PHPMA block and (ii)
      the total solids concentration at which the HPMA polymerization is conducted.
      Moreover, if the targeted diblock copolymer composition corresponds to vesicle
      phase space at full monomer conversion, the in situ particle morphology evolves
      from spheres to worms to vesicles during the in situ polymerization of HPMA. In
      the case of PMPC(25)-PHPMA(400) particles, this systematic approach allows the
      direct, reproducible, and highly efficient preparation of either block copolymer
      vesicles at up to 25% solids or well-defined worms at 16-25% solids in aqueous
      solution.

PMID- 21854066
TI  - Deviatoric stress driven formation of large single-crystal PbS nanosheet from
      nanoparticles and in situ monitoring of oriented attachment.
AB  - Two-dimensional single-crystal PbS nanosheets were synthesized by deviatoric
      stress-driven orientation and attachment of nanoparticles (NPs). In situ small-
      and wide-angle synchrotron X-ray scattering measurements on the same spot of the
      sample under pressure coupled with transmission electron microscopy enable
      reconstruction of the nucleation route showing how enhanced deviatoric stress
      causes ordering NPs into single-crystal nanosheets with a lamellar mesostructure.
      At the same time that deviatoric stress drives SC(110) orientation in a face
      centered-cubic supercrystal (SC), rocksalt (RS) NPs rotate and align their
      RS(200) and RS(220) planes within the SC(110) plane. When NPs approach each other
      along the compression axis, enhanced deviatoric stress drives soft ligands
      passivated at RS(200) and RS(220) surfaces to reorient from a group of SC(110) in
      planes to the interspace of SC[110]-normal planes. While the internal NP
      structure starts a rocksalt-to-orthorhombic transition at 7.1 GPa, NPs become
      aligned on RS(220) and RS(200) and thus become attached at those faces. The
      transition-catalyzed surface atoms accelerate the inter-NP coalescing process and
      the formation of low-energy structure nanosheet. Above 11.6 GPa, the nucleated
      single-crystal nanosheets stack into a lamellar mesostructure that has a domain
      size comparable to the starting supercrystal.

PMID- 21854067
TI  - Monoclonal antibody-based ELISA and colloidal gold immunoassay for detecting 19
      nortestosterone residue in animal tissues.
AB  - This article presents the generation of monoclonal antibodies (mAbs) with high
      specificity against 19-nortestosterone (NT) through cell fusion techniques and
      the development of a mAb-based indirect competitive ELISA (icELISA) method and
      colloidal gold-based immuno-chromatographic assay to detect NT residues in beef
      and pork samples. A modified carbodiimide method was employed to synthesize the
      artificial antigen, and BALB/c mice were used to produce anti-NT mAbs. On the
      basis of the checkerboard titration, an indirect competitive ELISA standard curve
      was established. This assay was sensitive and had a linear range from 0.03 to 38
      ng/mL in phosphate buffered saline (PBS), with IC(50) and LOD values of 0.52
      ng/mL and 0.01 ng/mL, respectively. Of all the competitive analogues, the
      produced mAb exhibited a high cross-reactivity to 17alpha-nortestosterone
      (83.6%), the main metabolite of NT in animal tissues. Except for moderate cross
      reactivities with trenbolone (22.6%) and beta-boldenone (13.8%), the other
      interference to the assay was negligible (<0.05%). In contrast, the strip test
      had a visual detection limit of 1 ng/mL in PBS, 2 MUg/kg in beef, and 2 MUg/kg in
      pork, respectively, and the results can be judged within 10 min. The ELISA and GC
      MS results showed close correlation in beef (R2=0.9945) and in pork (R2=0.9977).
      Therefore, the combination of two immunoassays provides a useful screening method
      for quantitative or qualitative detection of NT residues in animal-origin
      products.

PMID- 21854064
TI  - Phosphorylation of human eukaryotic initiation factor 2gamma: novel site
      identification and targeted PKC involvement.
AB  - Eukaryotic translation requires a suite of proteins known as eukaryotic
      initiation factors (eIFs). These molecular effectors oversee the highly regulated
      initiation phase of translation. Essential to eukaryotic translation initiation
      is the protein eIF2, a heterotrimeric protein composed of the individually
      distinct subunits eIF2alpha, eIF2beta, and eIF2gamma. The ternary complex, formed
      when eIF2 binds to GTP and Met-tRNA(i), is responsible for shuttling Met-tRNA(i)
      onto the awaiting 40S ribosome. As a necessary component for translation
      initiation, much attention has been given to the phosphorylation of eIF2alpha.
      Despite several previous investigations into eIF2 phosphorylation, most have
      centered on alpha- or beta-subunit phosphorylation and little is known regarding
      gamma-subunit phosphorylation. Herein, we report eight sites of phosphorylation
      on the largest eIF2 subunit with seven novel phosphosite identifications via high
      resolution mass spectrometry. Of the eight sites identified, three are located in
      either the switch regions or nucleotide binding pocket domain. In addition, we
      have identified a possible kinase of eIF2, protein kinase C (PKC), which is
      capable of phosphorylating threonine 66 (thr-66) on the intact heterotrimer.
      These findings may shed new light on the regulation of ternary complex formation
      and alternate molecular effectors involved in this process prior to 80S ribosome
      formation and subsequent translation elongation and termination.

PMID- 21854070
TI  - Molecular water motions of skim milk powder solutions during acidification
      studied by 17O and 1H nuclear magnetic resonance and rheology.
AB  - The molecular motion of water was studied in glucono-delta-lactone-acidified skim
      milk powder (SMP) solutions with various pH values and dry matter contents. NMR
      relaxometry measurements revealed that lowering the pH in SMP solutions affected
      17O and 1H T2 relaxation rates almost identically. Consequently, the present
      study indicates that the proteins present in the samples do not affect the 1H
      relaxation behavior markedly, even at relatively high SMP concentrations (15
      25%). Comparison of rheological measurements and NMR measurements suggested that
      the collapse of kappa-casein during acidification could contribute to the initial
      decrease in 17O and 1H relaxation rate in the pH range between 6.6 and 5.5 for
      15% SMP and in the pH range between 6.6 and 5.9 for 25% SMP. However, below pH
      5.5 the viscosity and 17O and 1H NMR relaxation rates did not correlate,
      revealing that the aggregation of casein micelles, which increases viscosity
      below pH 5.5, does not involve major repartitioning of water.

PMID- 21854069
TI  - Identification of key players for colorectal cancer metastasis by iTRAQ
      quantitative proteomics profiling of isogenic SW480 and SW620 cell lines.
AB  - This study compared the whole cell proteome profiles of two isogenic colorectal
      cancer (CRC) cell lines (primary SW480 cell line and its lymph node metastatic
      variant SW620), as an in vitro metastatic model, to gain an insight into the
      molecular events of CRC metastasis. Using iTRAQ (isobaric tags for relative and
      absolute quantitation) based shotgun proteomics approach, we identified 1140
      unique proteins, out of which 147 were found to be significantly altered in the
      metastatic cell. Ingenuity pathway analysis with those significantly altered
      proteins, revealed cellular organization and assembly as the top-ranked altered
      biological function. Differential expression pattern of 6 candidate proteins were
      validated by Western blot. Among these, the low expression level of beta-catenin
      combined with the up-regulation of CacyBP (Calcyclin binding Protein), a beta
      catenin degrading protein, in the metastatic cell provided a rational guide for
      the downstream functional assays. The relative expression pattern of these two
      proteins was further validated in three other CRC cells by Western blot and
      quantitative immunofluorescence studies. Overexpression of CacyBP in three
      different primary CRC cell lines showed significant reduction in adhesion
      characteristics as well as cellular beta-catenin level as confirmed by our
      experiments, indicating the possible involvement of CacyBP in CRC metastasis. In
      short, this study demonstrates successful application of a quantitative
      proteomics approach to identify novel key players for CRC metastasis, which may
      serve as biomarkers and/or drug targets to improve CRC therapy.

PMID- 21854068
TI  - Blood pressure lowering effect of a pea protein hydrolysate in hypertensive rats
      and humans.
AB  - The blood pressure lowering effect of a pea protein hydrolysate (PPH) that
      contained <3 kDa peptides, isolated by membrane ultrafiltration from the
      thermolysin digest of pea protein isolate (PPI), was examined using different rat
      models of hypertension as well as hypertensive human subjects. The PPH showed
      weak in vitro activities against renin and angiotensin converting enzyme (ACE)
      with inhibitory activities of 17 and 19%, respectively, at 1 mg/mL test
      concentration. Oral administration of the PPH to spontaneously hypertensive rats
      (SHR) at doses of 100 and 200 mg/kg body weight led to a lowering of hourly
      systolic blood pressure (SBP), with a maximum reduction of 19 mmHg at 4 h. In
      contrast, orally administered unhydrolyzed PPI had no blood pressure reducing
      effect in SHR, suggesting that thermolysin hydrolysis may have been responsible
      for releasing bioactive peptides from the native protein. Oral administration of
      the PPH to the Han:SPRD-cy rat (a model of chronic kidney disease) over an 8-week
      period led to 29 and 25 mmHg reductions in SBP and diastolic blood pressure,
      respectively. The PPH-fed rats had lower plasma levels of angiotensin II, the
      major vasopressor involved in development of hypertension, but there was no
      effect on plasma activity or renal mRNA levels of ACE. However, renal expression
      of renin mRNA levels was reduced by approximately 50% in the PPH-fed rats,
      suggesting that reduced renin may be responsible for the reduced levels of
      angiotensin II. In a 3-week randomized double blind placebo-controlled crossover
      human intervention trial (7 volunteers), significant (p<0.05) reductions (over
      placebo) in SBP of 5 and 6 mmHg were obtained in the second and third weeks,
      respectively, for the PPH group. Therefore, thermolysin derived bioactive
      peptides from PPH reduced blood pressure in hypertensive rats and human subjects,
      likely via effects on the renal angiotensin system.

PMID- 21854071
TI  - Electron microscopic imaging of a single Group 8 metal atom catalyzing C-C bond
      reorganization of fullerenes.
AB  - Heating a bulk sample of [60]fullerene complexes, (eta(5)-C(5)H(5))MC(60)R(5) (M
      = Fe, Ru, R = Me, Ph), produces small hydrocarbons because of coupling of R and
      C(5)H(5) via C-C and C-H bond activation. Upon observation by transmission
      electron microscopy, these complexes, encapsulated in single-walled carbon
      nanotubes, underwent C-C bond reorganization reactions to form new C-C bond
      networks, including a structure reminiscent of [70]fullerene. Quantitative
      comparison of the electron dose required to effect the C-C bond reorganization of
      fullerenes and organofullerenes in the presence of a single atom of Ru, Fe, or Ln
      and in the the absence of metal atoms indicated high catalytic activity of Ru and
      Fe atoms, as opposed to no catalytic activity of Ln. Organic molecules such as
      hydrocarbons and amides as well as pristine [60]fullerene maintain their
      structural integrity upon irradiation by ca. 100 times higher electron dose
      compared to the Ru and Fe organometallics. The results not only represent a rare
      example of direct observation of a single-metal catalysis but also have
      implications for the use of single metal atom catalysis in Group 8 metal
      heterogeneous catalysis.

PMID- 21854072
TI  - Collagen fibril orientation in ovine and bovine leather affects strength: a small
      angle X-ray scattering (SAXS) study.
AB  - There is a large difference in strength between ovine and bovine leather. The
      structure and arrangement of fibrous collagen in leather and the relationship
      between collagen structure and leather strength has until now been poorly
      understood. Synchrotron based SAXS is used to characterize the fibrous collagen
      structure in a series of ovine and bovine leathers and to relate it to tear
      strength. SAXS gives quantitative information on the amount of fibrous collagen,
      the orientation (direction and spread) of the collagen microfibrils, and the d
      spacing of the collagen. The amount of collagen varies through the thickness of
      the leather from the grain to the corium, with a greater concentration of
      crystalline collagen measured toward the corium side. The orientation index (OI)
      is correlated strongly with strength in ovine leather and between ovine and
      bovine leathers. Stronger leather has the fibrils arranged mostly parallel to the
      plane of the leather surface (high OI), while weaker leather has more out-of
      plane fibrils (low OI). With the measurement taken parallel to the animal's
      backbone, weak (19.9 N/mm) ovine leather has an OI of 0.422 (0.033), stronger
      (39.5 N/mm) ovine leather has an OI of 0.452 (0.033), and bovine leather with a
      strength of (61.5 N/mm) has an OI of 0.493 (0.016). The d-spacing profile through
      leather thickness also varies according to leather strength, with little
      variation being detected in weak ovine leather (average=64.3 (0.5) nm), but with
      strong ovine leather and bovine leather (which is even stronger) exhibiting a dip
      in d-spacing (from 64.5 nm at the edges dropping to 62 nm in the center). This
      work provides a clear understanding of a nanostructural characteristic of ovine
      and bovine leather that leads to differences in strength.

PMID- 21854073
TI  - Prediction of relative tissue proportions in wheat mill streams by fourier
      transform mid-infrared spectroscopy.
AB  - Fourier-transform mid-infrared (FTIR) spectroscopy was investigated as a method
      to quantify the relative wheat grain tissue proportion in milling fractions.
      Spectra were acquired with a FTIR spectrometer equipped with an attenuated total
      reflectance device on ground samples, and the relative tissue proportion was
      determined according to the biochemical marker methodology as the reference
      method. Partial least-squares models were developed independently to predict the
      amount of outer pericarp, aleurone layer, starchy endosperm, and an intermediate
      layer (made up of inner pericarp plus seed coat plus nucellar epidermis). Good
      quality of prediction was obtained regardless of the target tissue. The standard
      errors of prediction obtained for the outer pericarp, intermediate layer,
      aleurone layer, and starchy endosperm quantification were, respectively, 3.4,
      1.3, 3.4, and 4.6%.

PMID- 21854074
TI  - Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40)
      agonist with favorable physicochemical and in vitro ADME properties.
AB  - The free fatty acid receptor 1 (FFA1, also known as GPR40) enhances glucose
      stimulated insulin secretion from pancreatic beta-cells and is recognized as an
      interesting new target for treatment of type 2 diabetes. Several series of
      selective FFA1 agonists are already known. Most of these are derived from free
      fatty acids (FFAs) or glitazones and are relatively lipophilic. Aiming for the
      development of potent, selective, and less lipophilic FFA1 agonists, the terminal
      phenyl of a known compound series was replaced by nitrogen containing
      heterocycles. This resulted in the identification of 37, a selective FFA1 agonist
      with potent activity on recombinant human FFA1 receptors and on the rat
      insulinoma cell line INS-1E, optimal lipophilicity, and excellent in vitro
      permeability and metabolic stability.

PMID- 21854075
TI  - Folic acid conjugated amino acid-based star polymers for active targeting of
      cancer cells.
AB  - Amino acid-based core cross-linked star (CCS) polymers (poly(L-lysine)(arm)poly(L
      cystine)(core)) with peripheral allyl functionalities were synthesized by
      sequential ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides
      (NCAs) via the arm-first approach, using N-(trimethylsilyl)allylamine as the
      initiator. Subsequent functionalization with a poly(ethylene glycol) (PEG)-folic
      acid conjugate via thiol-ene click chemistry afforded poly(PEG-b-L
      lysine)(arm)poly(L-cystine)(core) stars with outer PEG coronas decorated with
      folic acid targeting moieties. Similarly, a control was prepared without folic
      acid, using just PEG. A fluorophore was used to track both star polymers
      incubated with breast cancer cells (MDA-MB-231) in vitro. Confocal microscopy and
      flow cytometry revealed that the stars could be internalized into the cells, and
      higher cell internalization was observed when folic acid moieties were present.
      Cytotoxicity studies indicate that both stars are nontoxic to MDA-MB-231 cells at
      concentrations of up to 50 MUg/mL. These results make this amino acid-based star
      polymer an attractive candidate in targeted drug delivery applications including
      chemotherapy.

PMID- 21854076
TI  - Identification of proline residues in or near the transmembrane helices of the
      human breast cancer resistance protein (BCRP/ABCG2) that are important for
      transport activity and substrate specificity.
AB  - The human breast cancer resistance protein (BCRP/ABCG2) confers multidrug
      resistance and mediates the active efflux of drugs and xenobiotics. BCRP contains
      one nucleotide-binding domain (NBD) followed by one membrane-spanning domain
      (MSD). We investigated whether prolines in or near the transmembrane helices are
      essential for BCRP function. Six proline residues were substituted with alanine
      individually, and the mutants were stably expressed in Flp-In(TM)-293 cells at
      levels comparable to that of wild-type BCRP and predominantly localized on the
      plasma membrane of the cells. While P392A showed a significant reduction (35-50%)
      in the efflux activity of mitoxantrone, BODIPY-prazosin, and Hoechst 33342, P485A
      exhibited a significant decrease of approximately 70% in the efflux activity of
      only BODIPY-prazosin. Other mutants had no significant changes in the efflux
      activities of these substrates. Drug resistance profiles of the cells expressing
      the mutants correlated well with the efflux data. ATPase activity was not
      substantially affected for P392A or P485A compared to that of wild-type BCRP.
      These results strongly suggest Pro(392) and Pro(485) are important in determining
      the overall transport activity and substrate selectivity of BCRP, respectively.
      Prazosin differentially affected the binding of 5D3, a conformation-sensitive
      antibody, to wild-type BCRP, P392A, or P485A in a concentration-dependent manner.
      In contrast, mitoxantrone had no significant effect on 5D3 binding. Homology
      modeling indicates that Pro(392) may play an important role in the communication
      between the MSD and NBD as it is predicted to be located at the interface between
      the two functional domains, and Pro(485) induces flexible hinges that may be
      essential for the broad substrate specificity of BCRP.

PMID- 21854077
TI  - Nonvolatile S-alk(en)ylthio-L-cysteine derivatives in fresh onion (Allium cepa L.
      cultivar).
AB  - The L-cysteine derivatives (R)-2-amino-3-(methyldisulfanyl)propanoic acid (S
      methylthio-L-cysteine), (R)-2-amino-3-(propyldisulfanyl)propanoic acid (S
      propylthio-L-cysteine), (R)-2-amino-3-(1-propenyldisulfanyl)propanoic acid (S-(1
      propenylthio)-L-cysteine), and (R)-2-amino-3-(2-propenyldisulfanyl)propanoic acid
      (S-allylthio-L-cysteine) were prepared from 3-[(methoxycarbonyl)dithio]-L
      alanine, obtained from the reaction of L-cysteine with methoxycarbonylsulfenyl
      chloride. The occurrence of these S-(+)-alk(en)ylthio-L-cysteine derivatives in
      onion (Allium cepa L.) was proven by using UPLC-MS-ESI(+) in SRM mode. Their
      concentrations in fresh onion were estimated to be 0.19 mg/kg S-methylthio-L
      cysteine, 0.01 mg/kg S-propylthio-L-cysteine, and 0.56 mg/kg (S-(1-propenyllthio)
      L-cysteine, concentrations that are about 3000 times lower than that of isoalliin
      (S-(1-propenyl-S-oxo-L-cysteine). These compounds were treated with Fusobacterium
      nucleatum, a microorganism responsible for the formation of mouth malodor. These
      L-cysteine disulfides were demonstrated to predominantly produce tri- and
      tetrasulfides. Isoalliin is almost entirely consumed by the plant enzyme alliin
      lyase (EC 4.4.1.4 S-alk(en)yl-S-oxo-L-cysteine lyase) in a few seconds, but it is
      not transformed by F. nucleatum. This example of flavor modulation shows that the
      plant produces different precursors, leading to the formation of the same types
      of volatile sulfur compounds. Whereas the plant enzyme efficiently transforms S
      alk(en)yl-S-oxo-L-cysteine, mouth bacteria are responsible for the transformation
      of S-alk(en)ylthio-L-cysteine.

PMID- 21854078
TI  - Structure-activity relationships of 4-position diamine quinoline methanols as
      intermittent preventative treatment (IPT) against Plasmodium falciparum.
AB  - A library of diamine quinoline methanols were designed based on the mefloquine
      scaffold. The systematic variation of the 4-position amino alcohol side chain led
      to analogues that maintained potency while reducing accumulation in the central
      nervous system (CNS). Although the mechanism of action remains elusive, these
      data indicate that the 4-position side chain is critical for activity and that
      potency (as measured by IC(90)) does not correlate with accumulation in the CNS.
      A new lead compound, (S)-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)-2-(2
      (cyclopropylamino)ethylamino)ethanol (WR621308), was identified with single dose
      efficacy and substantially lower permeability across MDCK cell monolayers than
      mefloquine. This compound could be appropriate for intermittent preventative
      treatment (IPTx) indications or other malaria treatments currently approved for
      mefloquine.

PMID- 21854079
TI  - Patient benefit-risk preferences for targeted agents in the treatment of renal
      cell carcinoma.
AB  - BACKGROUND: Angiogenesis inhibitor agents have been shown to be effective in
      increasing progression-free survival (PFS) in patients with renal cell carcinoma
      (RCC); however, these treatments have different toxicity profiles. OBJECTIVE: Our
      objective was to quantify patients' benefit-risk preferences for RCC treatments
      and relative importance of attributes in a common metric. METHODS: US residents
      aged >=18 years with RCC completed a web-enabled, choice-format conjoint survey
      that presented a series of 12 trade-off questions, each including a pair of
      hypothetical RCC treatment profiles. Each profile was defined by efficacy (PFS,
      when overall survival held constant), tolerability effects (fatigue/tiredness,
      diarrhoea, hand-foot syndrome [HFS], mouth sores) and serious adverse events
      (liver failure, blood clot). Trade-off questions were based on a predetermined
      experimental design with known statistical properties. Random-parameters logit
      was used to analyse the data. RESULTS: A total of 138 patients completed the
      survey. PFS was the most important attribute for patients over the range of
      levels included in the survey, while remaining attributes were ranked in
      decreasing order of importance: fatigue/tiredness, diarrhoea, liver failure, HFS,
      blood clot and mouth sores. In order to increase PFS by 11 months, patients would
      be willing to accept a maximum level of absolute blood clot risk of 3.1% (95% CI
      1.5, 5.3) or liver failure risk of 2.0% (95% CI 1.0, 3.3). CONCLUSION: A 22-month
      change in PFS was shown to be the most important improvement for patients. Severe
      fatigue/tiredness and diarrhoea were rated as the most troublesome tolerability
      effects of RCC treatment. Patients were likely willing to accept significant
      treatment-related risks of 2-3% for liver failure and blood clot to increase PFS
      by 11 months.

PMID- 21854081
TI  - A dosing regimen for immediate N-acetylcysteine treatment for acute paracetamol
      overdose.
AB  - CONTEXT: Current treatment of paracetamol (acetaminophen) poisoning involves
      initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma
      concentration, taken >= 4 h post-overdose, to a nomogram. This may result in
      dosing errors, a delay in treatment, or possibly more adverse effects - due to
      the use of a high dose rate for the first infusion when treatment is initiated.
      OBJECTIVE: Our aim was to investigate a novel dosing regimen for the immediate
      administration of NAC on admission at a lower infusion rate. METHODS: We used a
      published population pharmacokinetic model of NAC to simulate a scenario where a
      patient presents to the hospital 2 h post-overdose. The conventional regimen is
      commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is
      available. We investigated an NAC infusion using a lower dosing rate initiated
      immediately on presentation. We determined a dosing rate that gave an area under
      the curve (AUC) of the concentration-time curve that was the same or greater than
      that from the conventional regimen on 90% of occasions. RESULTS: Lower dosing
      rates of NAC initiated immediately resulted in a similar exposure to NAC. An
      infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two
      phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed
      by the last phase of the conventional regimen could be used. CONCLUSION: The
      novel dosing regimen allowed immediate treatment of a patient using a lower
      dosing rate. This greatly simplifies the current dosing regimen and may reduce
      NAC adverse effects while ensuring the same amount of NAC is delivered.

PMID- 21854080
TI  - Denosumab for the prevention of osteoporotic fractures in post-menopausal women:
      a NICE single technology appraisal.
AB  - The National Institute for Health and Clinical Excellence (NICE) invited the
      manufacturer of denosumab (Amgen Inc., UK) to submit evidence for the clinical
      and cost effectiveness of denosumab for the prevention of fragility fractures in
      post-menopausal women, as part of the Institute's single technology appraisal
      (STA) process. The University of Aberdeen Health Technology Assessment Group were
      commissioned to act as the Evidence Review Group (ERG); the role of the ERG being
      to appraise the manufacturer's submission and to produce an independent report.
      This article provides a description of the company submission, the ERG review and
      NICE's subsequent decisions. The manufacturer considered that denosumab would be
      appropriate for patients unable to take, comply with or tolerate oral
      bisphosphonates. Comparator treatments selected for the submission were,
      therefore, 'no treatment', raloxifene, strontium ranelate, intravenous zoledronic
      acid, intravenous ibandronate and teriparatide. The main effectiveness evidence
      for denosumab was derived from a large randomized controlled trial comparing
      denosumab with placebo. Given by subcutaneous injection at 6-monthly intervals
      for 3 years, denosumab reduced the incidence of hip fracture by 40%, and reduced
      the incidence of clinical vertebral fracture by 69%. An indirect treatment
      comparison was used to derive adjusted relative risk (RR) estimates for different
      types of fracture for each comparator versus placebo. The RRs (95% CI) applied
      for denosumab were 0.316 (0.208, 0.478) for clinical vertebral fracture, 0.605
      (0.373, 0.983) for hip fracture and 0.842 (0.638, 1.110) for wrist fracture.
      Despite a number of concerns surrounding the methodology of the indirect
      comparison, the ERG was satisfied with the robustness of the effect estimates.
      The RR estimates were applied in a good-quality Markov model that took account of
      drug costs, administration and monitoring costs, costs associated with fractures,
      and long-term nursing home costs. Utility weights were used to adjust time spent
      in fracture states, allowing QALYs to be estimated. The base-case analysis was
      conducted for women aged 70 years with a T-score of -2.5 or less and no prior
      fracture, and women aged 70 years with a T-score of -2.5 or less with a prior
      fragility fracture. Subgroup analyses based on T-score and independent clinical
      risk factors were also undertaken. Applying a willingness-to-pay (WTP) threshold
      of L30 000 per QALY, the manufacturer's results suggested that denosumab would
      offer a cost-effective alternative to all treatment comparators for the primary
      and secondary prevention of fractures. The ERG was concerned about an assumption
      that denosumab would be administered in general practice at the average cost of
      two standard GP visits a year. As a result, the ERG requested some further
      sensitivity analysis and undertook some further modelling, applying an assumption
      that denosumab would be provided primarily in secondary care. This modification
      altered the cost effectiveness of denosumab versus 'no treatment' (in women with
      no prior fragility fracture) and zoledronic acid. The NICE Appraisal Committee
      concluded that, as a treatment option for the prevention of osteoporotic
      fractures, denosumab should be recommended only in post-menopausal women at
      increased risk of fracture who cannot comply with the special instructions for
      administering oral bisphosphonates, or have an intolerance of, or
      contraindication to, those treatments. For primary prevention, the Appraisal
      Committee also stipulated specific levels of fracture risk at which denosumab is
      recommended.

PMID- 21854082
TI  - Distinct clonal deletions of the long arm of chromosome 5 in a patient with
      myelodysplastic syndrome.

PMID- 21854083
TI  - Associations between non-Hodgkin lymphoma and renal cell carcinoma.

PMID- 21854084
TI  - Mechanisms regulating enhanced human leukocyte antigen class II-mediated CD4 + T
      cell recognition of human B-cell lymphoma by resveratrol.
AB  - Malignant B-cells express measurable levels of human leukocyte antigen (HLA)
      class II proteins, but often escape immune recognition by CD4 + T cells.
      Resveratrol (Resv) has been the focus of numerous investigations due to its
      potential chemopreventive and anti-cancer effects, but it has never been tested
      in the regulation of immune components in B-cell tumors. Here, we show for the
      first time that Resv treatment enhances HLA class II-mediated immune detection of
      B-cell lymphomas by altering immune components and class II presentation in tumor
      cells. Resv treatment induced an up-regulation of both classical and non
      classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also
      altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT),
      increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and
      their subsequent recognition by CD4 + T cells. Mechanistic study demonstrated
      that Resv treatment activated the recycling class II pathway of Ag presentation
      through up-regulation of Rab 4B protein expression in B-lymphoma cells. These
      findings suggest that HLA class II-mediated immune recognition of malignant B
      cells can be improved by Resv treatment, thus encouraging its potential use in
      chemoimmunotherapy of B-cell lymphoma.

PMID- 21854085
TI  - Allogeneic stem cell transplant for adult Philadelphia chromosome-negative acute
      lymphoblastic leukemia.
AB  - Performing not only related but also unrelated allogeneic stem cell transplant
      (allo-SCT) for adult Philadelphia chromosome-negative acute lymphoblastic
      leukemia [Ph(-) ALL] during first complete remission (CR) may be a potent
      therapeutic strategy for long-term survival. The survival times after related or
      unrelated allo-SCT may be comparable, but different background risk factors
      arising from differences in donor types should be recognized to improve the
      outcome of allo-SCT. In addition, age should be considered as an important
      factor. In adolescents and young adults, for whom intensified pediatric protocols
      show promise for improving outcomes, minimal residual disease may be helpful for
      making the decision to conduct allo-SCT during first CR. For older adults,
      however, reduced intensity conditioning (RIC) could expand the indication for
      allo-SCT for Ph(-) ALL in CR. Since the non-relapse mortality of allo-SCT remains
      significantly high compared with that of conventional chemotherapy, careful
      selection of patients is mandatory. However, it is crucial not to miss the
      correct timing of allo-SCT, given that the prognosis of relapsed ALL is very
      dismal. After close consideration of donor type, patient age, response to
      chemotherapy and appropriate timing, the outcome of allo-SCT for adult Ph(-) ALL
      could be improved.

PMID- 21854086
TI  - Trisomy 8 in Philadelphia chromosome negative cell preceding the evolution of a
      Philadelphia chromosome positive clone with the same additional change during
      imatinib treatment: revisiting the role of genetic instability in chronic myeloid
      leukemia.

PMID- 21854087
TI  - Rituximab in space: intrapleural and other novel routes of administration for
      lymphomas and lymphoid leukemias.

PMID- 21854088
TI  - Developing a model for online support group use, empowering processes and
      psychosocial outcomes for individuals living with HIV/AIDS.
AB  - This study examined the mechanism through which online support group (OSG)
      participation may promote patient empowerment among 340 individuals living with
      HIV/AIDS. Results from structural equation modelling revealed that greater use of
      OSGs was associated with more frequent occurrence of the empowering processes as
      measured by receiving useful information, receiving social support, finding
      positive meaning and helping others. Receiving useful information and finding
      positive meaning were related to higher levels of adaptive coping and lower
      levels of maladaptive coping, while receiving social support and helping others
      were related to higher levels of self-care self-efficacy, which in turn was
      related to higher levels of adaptive coping, and lower levels of maladaptive
      coping. Finally, higher levels of maladaptive coping were related to poorer
      quality of life, while higher levels of adaptive coping were related to better
      quality of life. Results suggest that OSG participation may offer some benefits
      for those living with HIV/AIDS.

PMID- 21854089
TI  - Cloning and partial characterization of a novel hemolysin gene of Vibrio
      tubiashii and the development of a PCR-based detection assay.
AB  - Vibrio tubiashii expresses virulence factors, such as a vulnificolysin-like
      hemolysin or cytolysin and a zinc metalloprotease, similar to those of other
      pathogenic vibrios. In this study, we report the cloning of a novel hemolysin
      gene of V. tubiashii in Escherichia coli . A V. tubiashii gene library was
      screened for hemolytic activity on sheep blood agar. Three hemolytic clones
      pGem:hly1, pGem:hly2, and pGem:hly3 were sequenced, and the sequences showed a
      strong homology to the ribA gene coding for guanosine triphosphate cyclohydrolase
      II (GCH II), required for riboflavin biosynthesis and reported to be responsible
      for hemolytic activity in Helicobacter pylori . The plasmids pGem:hly1 and
      pGem:hly3 when introduced into E. coli BSV18 (ribA18::Tn5) were able to restore
      growth of strain BSV18 in a medium without riboflavin and also produced hemolytic
      activity on blood agar. PCR primers based on the cloned hly-ribA sequence were
      tested using 23 different Vibrio strains representing 10 different species.
      Amplification of ribA gene locus only occurred with V. tubiashii strains. In
      summary, our results indicate that we have cloned a ribA homolog of V. tubiashii
      that imparts hemolytic activity to E. coli clones, and primers based on this gene
      locus might be useful as a species-specific identification tool for V. tubiashii.

PMID- 21854091
TI  - J-shaped versus median sternotomy for aortic valve replacement with minimal
      extracorporeal circuit.
AB  - OBJECTIVES: Minimal access aortic valve replacement (AVR) has been demonstrated
      to have beneficial effects over median sternotomy. Minimal extracorporeal
      circulation (MECC) has been shown to have less deleterious effects than
      conventional cardiopulmonary bypass. We describe for the first time AVR via upper
      J-shaped partial sternotomy compared to median sternotomy using MECC. METHODS:
      Prospectively collected pre-operative, intra-operative, post-operative and follow
      up data from 104 consecutive patients who underwent minimal access AVR were
      compared to 72 consecutive patients undergoing median sternotomy using MECC
      during the same period (January 2007 to December 2009). RESULTS: No significant
      differences were found in patient's characteristics or intra-operative data with
      the exception of pre-existing pulmonary disease. The mean cardiopulmonary bypass
      (86 +/- 18 min vs. 78 +/- 15 min, p = 0.0079) and cross-clamp times (65 +/- 13
      min vs. 59 +/- 12 min, p = 0.0013) were significantly shorter in the median
      sternotomy group. Mediastinal blood loss (397 +/- 257 ml vs. 614 +/- 339 ml, p <
      0.0001) and ventilation time (8 +/- 6.9 h vs. 11 +/- 16.5 h, p = 0.0054) were
      significantly less in the minimal access group. No differences were seen in
      transfusion requirements, inotropic support, intensive care unit (ICU) stay,
      total hospital stay, post-operative haemoglobin drop, major events or mortality.
      Quality of life scores after discharge demonstrated less pain with a quicker
      recovery and return to daily activities in patients receiving J-shaped
      sternotomy. CONCLUSIONS: Minimal access AVR using MECC is feasible and provides
      excellent clinical results. Less pain and quicker recovery was experienced among
      patients in this group.

PMID- 21854092
TI  - Establishment and assessments of a new model for the postoperative fatigue
      syndrome by major small intestinal resection in rats.
AB  - OBJECTIVE: Postoperative fatigue syndrome (POFS) is a general and main
      complication after surgery. However, there is no stable and standardized animal
      model for POFS. The aim of the present study was to establish a rodent model of
      POFS by small intestinal resection, with POFS evaluated by acknowledged physical
      and behavioral methods. MATERIAL AND METHODS: Forty-two Sprague-Dawley rats were
      randomly divided into four groups according to the length of a "middle" small
      intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70%
      groups, with corresponding lengths of small intestinal resections. Following
      surgery, the general state of health was evaluated. Tail suspension test, open
      field test and Morris water maze test were used to evaluate the degree of POFS.
      Serum albumin, transferrin, prealbumin and fibronectin were measured to assess
      the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA)
      were also measured. RESULTS: As compared with the other three groups, the 70%
      small intestinal resection group showed the worst general state of health,
      decreased strength of the tail suspension test and decreased score of Morris
      water maze test (p < 0.05) after operation. All rats in whom the small intestinal
      resection was done demonstrated a certain degree of malnutrition and behavior of
      depression, and the 70% resection group had the lowest levels of transferrin,
      prealbumin and fibronectin as compared with the other groups (p < 0.05), as well
      as decreased SOD and increased MDA in serum (p < 0.05). CONCLUSIONS: Resection of
      70% of the small intestine resulted in typical characteristics of POFS. As this
      procedure is simple, stable and easily reproducible, it may serve as a model for
      research on POFS.

PMID- 21854090
TI  - The forensic nursing in sexual assaults: the immunochemical diagnosis and
      prevention of its adverse effects.
AB  - Sexual assault was a ubiquitous and serious problem in our society. The world's
      care centers and forensic associations, which were at the forefront of scientific
      research in sexual assaults, discussed the role of the Forensic Nursing in their
      early diagnosis and their prevention, but little has been written in literature
      regarding their appropriate management. This article focuses on the
      immunochemical laboratory investigation in diagnosis and prevention of its
      adverse effects in sexual assaults and the role of the Forensic Nursing played in
      this task. After a careful reading of all the material received from many of the
      care centers and the associations contacted, a Forensic Nursing Examination
      Program, with specific immunochemical address, is identified.

PMID- 21854093
TI  - Post-remission intervention with alemtuzumab or rituximab to eradicate minimal
      residual disease in chronic lymphocytic leukemia: where do we stand?
AB  - The introduction of purine nucleoside analogs, later in combination with
      alkylating moieties and anti-CD20 immunotherapy, has profoundly improved the
      response rate and response duration in patients with chronic lymphocytic leukemia
      (CLL). The quality of clinical response following treatment may be improved to a
      level where residual leukemic cells become undetectable. As patients with this
      type of response appear to have extended survival rates, minimal residual disease
      (MRD) eradication is considered a new objective in CLL treatment with the aim of
      improving progression-free survival (PFS) and potentially overall survival (OS).
      This review therefore aims to overview the prognostic value of MRD eradication in
      CLL, the role of post-remission intervention with "passive" immunotherapy
      (alemtuzumab or rituximab) so as to eliminate persistent MRD or prevent MRD
      relapse, the impact of these strategies on disease-free survival and their
      possible adverse consequences. The data indicate a potential for post-remission
      alemtuzumab or rituximab to prolong PFS in CLL, although more investigations and
      longer follow-up are required before MRD-guided strategies can be recommended
      outside of clinical trials.

PMID- 21854095
TI  - Adenocarcinoma of the ampulla of Vater: does the histopathologic type matter?

PMID- 21854096
TI  - Is smoking a risk factor for collagenous colitis?
AB  - OBJECTIVE: The association between smoking and idiopathic inflammatory bowel
      disease is well known; smoking seems to have a diverse effect. Crohn's disease is
      associated with smoking, while ulcerative colitis is associated with non-smoking.
      Data on smoking in microscopic colitis of the collagenous type (CC) are lacking.
      The aim of this investigation was to study smoking habits in CC and to observe
      whether smoking had any impact on the course of the disease. MATERIALS AND
      METHODS: 116 patients (92 women) with median age of 62 years (interquartile range
      55-73) answered questionnaires covering demographic data, smoking habits and
      disease activity. As control group we used data from the general population in
      Sweden retrieved from Statistics Sweden, the central bureau for national
      socioeconomic information. RESULTS: Of the 116 CC patients, 37% were smokers
      compared with 17% of controls (p < 0.001, odds ratio (OR) 2.95). In the age group
      16-44 years, 75% of CC patients were smokers compared with 15% of controls (p <
      0.001, OR 16.54). All CC smoker patients started smoking before the onset of
      disease. Furthermore, smokers developed the disease earlier than non-smokers--at
      42 years of age (median) compared with 56 years in non-smokers (p < 0.003).
      Although the proportion with active disease did not differ between smokers and
      non-smokers, there was a trend indicating that more smokers received active
      treatment (42% vs. 17%, p = 0.078). CONCLUSIONS: Smoking is a risk factor for CC.
      Smokers develop their disease more than 10 years earlier than non-smokers.

PMID- 21854098
TI  - Staphylococcus sciuri exfoliative toxin C is a dimer that modulates macrophage
      functions.
AB  - Staphylococcus sciuri causes multiple infections in humans. Recently, a strain of
      S. sciuri (HBXX06) carrying exfoliative toxin C (ExhC) was reported to cause
      fatal exudative epidermal skin pathology in piglets and might be considered as a
      potential zoonotic agent. However, little is known about the pathogenicity of
      this bacterium. In this study, we examined the activity of recombinant ExhC-his
      (rExhC) protein using newborn mice as the model and investigated the effect of
      rExhC on macrophage functions. Interestingly, we found that both rExhC and S.
      sciuri ExhC existed as dimers and that rExhC inhibited the phagocytosis of
      RAW264.7 cell lines but enhanced the production of proinflammatory mediators,
      such as interleukin-6, interleukin-12, tumor necrosis factor alpha, and nitric
      oxide, by murine peritoneal macrophages and RAW264.7 cells. These results suggest
      that ExhC may play an important role in innate immune response against S. sciuri
      infection.

PMID- 21854097
TI  - Inhibition effects of isolated compounds from Artemisia rubripes Nakai of the
      classical pathway on the complement system.
AB  - The study evaluated the anticomplement activity from isolated compounds from
      Artemisia rubripes Nakai from South Korea on the classical pathway. In the
      previous works, Artemisia rubripes chloroform extracts showed inhibitory activity
      against complement system. The chromatographic separation of a chloroform
      chloride extract of Artemisia rubripes led to the isolation of three compounds.
      Their structures were characterized to be scopoletin (1), 11,(13)-triene-6,12
      olide (2), and 1beta,6alpha-dihydroxy-4(15)-eudesmene (3) by spectroscopic data.
      This is the first report of anticomplement activity of isolated compounds from
      Artemisia rubripes.

PMID- 21854094
TI  - Screening for colorectal cancer: possible improvements by risk assessment
      evaluation?
AB  - Emerging results indicate that screening improves survival of patients with
      colorectal cancer. Therefore, screening programs are already implemented or are
      being considered for implementation in Asia, Europe and North America. At
      present, a great variety of screening methods are available including colono- and
      sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood
      in feces, and so on. The pros and cons of the various tests, including economic
      issues, are debated. Although a plethora of evaluated and validated tests even
      with high specificities and reasonable sensitivities are available, an
      international consensus on screening procedures is still not established. The
      rather limited compliance in present screening procedures is a significant
      drawback. Furthermore, some of the procedures are costly and, therefore,
      selection methods for these procedures are needed. Current research into
      improvements of screening for colorectal cancer includes blood-based biological
      markers, such as proteins, DNA and RNA in combination with various
      demographically and clinically parameters into a "risk assessment evaluation"
      (RAE) test. It is assumed that such a test may lead to higher acceptance among
      the screening populations, and thereby improve the compliances. Furthermore, the
      involvement of the media, including social media, may add even more individuals
      to the screening programs. Implementation of validated RAE and progressively
      improved screening methods may reform the cost/benefit of screening procedures
      for colorectal cancer. Therefore, results of present research, validating RAE
      tests, are awaited with interest.

PMID- 21854099
TI  - Prognostic value of lymph-node dissection in patients undergoing radical
      cystectomy following previous oncological treatment for bladder cancer.
AB  - OBJECTIVE: To investigate the prognostic value of lymph-node dissection (LND) in
      patients undergoing radical cystectomy (RC) following previous oncological
      treatment. MATERIAL AND METHODS: Perioperative findings and recurrence patterns
      of 46 patients undergoing RC for bladder cancer were evaluated. Twenty-six
      patients underwent salvage cystectomy because of local bladder cancer recurrence
      following intended curative external beam radiotherapy; 20 patients underwent
      preoperative chemotherapy because of non-regional lymph-node metastases (10
      patients), clinically fixed primary tumour (cT4b) (eight patients) or pulmonary
      metastases (two patients). RESULTS: Difficulties with LND because of fibrous
      tissue were accounted in the majority of previously irradiated patients. No
      metastatic lymph nodes were found within the irradiation field at the time of
      surgery or during follow-up. Two- and 5-year disease-specific survival (DSS) was
      47% and 31%, respectively. In patients undergoing preoperative chemotherapy
      because of lymph-node metastasis, three patients (30%) had vital tumour cells
      within the removed lymph-nodes. Two- and 5-year DSS was 67% and 50%,
      respectively. Despite preoperative chemotherapy, all patients with cT4b tumours
      and previously diagnosed pulmonary metastases died because of recurrent disease
      within 2 years. CONCLUSIONS: LND in the previously irradiated pelvis may be
      difficult and remains controversial. Because of a high risk of vital tumours
      cells within the removed lymph nodes despite chemotherapy, extended LND should be
      performed in patients with non-regional lymph-node metastasis following
      preoperative chemotherapy. In patients with fixed tumours and minimal response to
      chemotherapy and in patients with visceral metastases, RC should be attempted for
      palliative reasons only.

PMID- 21854100
TI  - Bilateral vanished testes diagnosed with a single blood sample showing very high
      gonadotropins (follicle-stimulating hormone and luteinizing hormone) and very low
      inhibin B.
AB  - OBJECTIVE: In boys with cryptorchidism median serum values of follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) are higher and median
      serum values of inhibin B lower than in normal controls. Serum values of inhibin
      B reflect the state of germinative epithelium in cryptorchid testes. The aim of
      the study was to evaluate whether a simple blood sample of gonadotropins and
      inhibin B could diagnose bilateral vanished testes. MATERIAL AND METHODS: Group I
      included five boys (4 months to 6 years and 3 months old) with bilateral vanished
      testes at laparoscopy. Group II included 82 boys with bilateral cryptorchidism
      younger than 7 years of age at surgery for bilateral cryptorchidism (median age 1
      year and 9 months). RESULTS: The serum levels of hormones for the patients with
      vanished testes were: inhibin B 5?18 pg/ml, FSH 41-191 IU/l and LH 3.9?56 IU/l.
      The patients all had karyotype 46,xy. The serum levels of hormones from group II
      were: inhibin B median 122 (range 20?404) pg/ml, FSH median 0.8 (range 0.2?3.5)
      IU/l and LH median 0.2 (range 0.1-3.2) IU/l. The serum levels of inhibin B, FSH
      and LH from the boys with vanished testes were significantly different from the
      serum levels of the boys with bilateral cryptorchidism (p = 0.0026, p < 0.0001
      and p < 0.0001, respectively). CONCLUSIONS: The serum values of gonadotropins and
      inhibin B from boys with bilateral vanished testes were significantly different
      from those of bilateral cryptorchid boys, indicating no germinative epithelium,
      no Sertoli cells and compensatory high gonadotropins. If such abnormal serum
      values are obtained from boys with bilateral non-palpable testes, tubular tissue
      is not present and surgery can be avoided.

PMID- 21854102
TI  - Anti-allergic effect of lambertianic acid from Thuja orientalis in mouse bone
      marrow-derived mast cells.
AB  - Lambertianic acid is a bioactive diterpene found in the leaves of Thuja
      orientalis. Its effect on the bone marrow-derived mast cell (BMMC) mediated
      allergy and inflammation mechanism remains unknown. In this study, lambertianic
      acid was evaluated for its effect on the allergic mediators, including
      prostaglandin D(2) (PGD(2)), leukotriene C(4) (LTC(4)), beta-hexosaminidase (beta
      Hex) and cyclooxygenase-2 (COX-2) protein, in phorbol 12-myristate 13-acetate
      (PMA) plus calcimycin-stimulated BMMCs. The results revealed that lambertianic
      acid inhibited the production of interleukin-6 (IL-6), PGD(2) and LTC(4), the
      expression of COX-2 and the degranulation of beta-hexosaminidase in the PMA plus
      calcimycin-induced BMMCs. Taken together, these findings implied that
      lambertianic acid may possess the potential in the treatment of allergy.

PMID- 21854101
TI  - Long-term follow-up after radical cystectomy with emphasis on complications and
      reoperations: a Swedish population-based survey.
AB  - OBJECTIVE: To evaluate outcome after radical cystectomy for primary bladder
      cancer in a large population-based material. MATERIAL AND METHODS: Between 1997
      and 2002 all patients treated with radical cystectomy within 3 months after
      diagnosis of primary bladder cancer without distant metastasis were retrieved
      through the Swedish Bladder Cancer Registry. A follow-up questionnaire was
      distributed to all units where the primary registration of patients was
      performed. Follow-up data on recurrence date were retrieved from the patient
      charts and causes of death were obtained from the Swedish Cause of Death Registry
      until 2003. RESULTS: During the study period radical cystectomy was performed in
      39 units in Sweden, of which only five units were considered high-volume
      hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml
      (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in
      high-volume units than in hospitals with lower hospital volumes, but the 90-day
      mortality rates were similar. During a median follow-up of 3.5 years, 24% of the
      patients were submitted to a reoperation. Reoperation rates were significantly
      higher in patients who received a continent urinary diversion (29%) compared with
      an ileal conduit (22%, p < 0.015). CONCLUSIONS: Radical cystectomy was associated
      with a reoperation rate of 24% in Sweden during the study period. The reoperation
      rates were higher in patients receiving a continent cutaneous diversion or
      bladder substitution. Blood loss was higher in high-volume units; otherwise,
      surgical volume did not affect mortality rates, cancer-specific survival or
      reoperation rates.

PMID- 21854103
TI  - Development of a person-centred lifestyle intervention for older adults following
      a stroke or transient ischaemic attack.
AB  - BACKGROUND: Older adults with mild to moderate stroke or transient ischaemic
      attack often experience anxiety, depression and reduced social participation in
      their daily lives. Interventions addressing the long-term consequences of stroke
      are needed. OBJECTIVE: To describe the process of developing a person-centred
      lifestyle intervention for older adults with stroke. METHODS: The Canadian
      Occupational Performance Measure was used to develop the content of the
      intervention. Lifestyle groups were implemented at senior centres once a week for
      nine months. Content analysis was used to analyse the intervention content.
      RESULTS: A total of 132 participants (median age 79 years, 55% women, 52% lived
      alone) were recruited from hospitals. The participants prioritized 392
      occupational problems, mainly related to active recreation, household and
      community management, mobility, and socialization. The occupational issues were
      addressed in the group interventions. New themes also emerged in line with the
      participants' choices through group discussions, such as information on stroke
      and prevention of new strokes, outdoor mobility and transportation, "brain use"
      and memory. CONCLUSION: The study demonstrates the development of intervention
      following stroke, addressing its process, structure, and components. Whether the
      person-centred process increases the potential for enhancing participants' social
      participation and well-being should be evaluated in future studies.

PMID- 21854104
TI  - The impact of adjustment latitude on self-assessed work ability in regard to
      gender and occupational type.
AB  - OBJECTIVE: Adjustment latitude describes opportunities to change demands at work
      when ill and may affect work ability. The aim here is to study the association
      between adjustment latitude and self-assessed work ability among men and women
      and employees from different occupational sectors. METHODS: This cross-sectional
      study used data from a questionnaire sent to 3020 employees in three occupational
      sectors in Sweden; 1430 responded. Subjects were divided into: full, moderately
      reduced, and greatly reduced work ability. Presence of nine adjustment
      opportunities was requested and subjects were divided into three groups. Each
      specific opportunity was also analyzed in relation to work ability. Multinomial
      logistic regression was used for analyses. RESULTS: Number of opportunities to
      adjust was associated with work ability among men and employees in health care.
      "Shortening the working day" was associated with work ability in most groups. For
      men and industrial employees, "postponing work", "going home and working later",
      and "working without disturbance" were associated with work ability. "To work
      from home" was associated with work ability among women and employees in
      insurance. CONCLUSIONS: The assumption that adjustment latitude affects work
      ability is supported. Associations differ with regard to gender and occupational
      sectors. Further studies with longitudinal design and alternative samples are
      needed.

PMID- 21854105
TI  - Urinary heavy metals and associated medical conditions in the US adult
      population.
AB  - Health effects of heavy metals have been widely investigated, but further
      evaluation is required to comprehensively delineate their toxicity. Using data
      from the 2007-2008 National Health and Nutrition Examination Survey, a
      multivariate logistic regression analysis was performed on 1,857 adults to
      examine the relationship between urinary heavy metals and various medical
      conditions. Cardiovascular diseases were correlated to cadmium (OR: 4.94, 95% CI:
      1.48-16.56) and lead (OR: 5.32, 95% CI: 1.08-26.21). Asthma was related to
      tungsten (OR: 1.72, 95% CI: 1.15-2.59) and uranium (OR: 1.52, 95% CI: 1.01-2.28).
      Hepatotoxicity was associated with molybdenum (OR: 3.09, 95% CI: 1.24-7.73) and
      uranium (OR: 4.79, 95% CI: 1.74-13.19). Surprising inverse relationships occurred
      for excessive weight with lead (OR: 0.72, 95% CI: 0.52-0.98), reduced visual
      acuity with cobalt (OR: 0.65, 95% CI: 0.44-0.95) and cesium (OR: 0.52, 95% CI:
      0.35-0.77). This study supports some previous evidence of potential relationships
      and provides insights for future research.

PMID- 21854108
TI  - The water balance questionnaire: design, reliability and validity of a
      questionnaire to evaluate water balance in the general population.
AB  - There is a need to develop a questionnaire as a research tool for the evaluation
      of water balance in the general population. The water balance questionnaire (WBQ)
      was designed to evaluate water intake from fluid and solid foods and drinking
      water, and water loss from urine, faeces and sweat at sedentary conditions and
      physical activity. For validation purposes, the WBQ was administrated in 40
      apparently healthy participants aged 22-57 years (37.5% males). Hydration indices
      in urine (24 h volume, osmolality, specific gravity, pH, colour) were measured
      through established procedures. Furthermore, the questionnaire was administered
      twice to 175 subjects to evaluate its reliability. Kendall's tau-b and the Bland
      and Altman method were used to assess the questionnaire's validity and
      reliability. The proposed WBQ to assess water balance in healthy individuals was
      found to be valid and reliable, and it could thus be a useful tool in future
      projects that aim to evaluate water balance.

PMID- 21854107
TI  - Inhibition of LPS-induced inflammatory biomarkers by ethyl acetate fraction of
      Patrinia scabiosaefolia through suppression of NF-kappaB activation in RAW 264.7
      cells.
AB  - Patrinia scabiosaefolia (PS) has been used for curing various types of
      inflammatory-related disorders. However, the precise mechanism of the anti
      inflammatory activity of PS remains unclear. Here, we investigated the anti
      inflammatory effects of several fractions isolated from the PS in RAW 264.7
      macrophages. The results indicated that the ethyl acetate fraction of PS (EAPS)
      concentration highly suppressed lipopolysaccharide (LPS)-induced nitric oxide
      (NO) and IL-6 productions without a cytotoxic effect on RAW 264.7 cells. EAPS
      inhibited the expressions of LPS-induced iNOS and COX-2 protein and their mRNA in
      a dose-dependent manner. Particularly, EAPS suppressed the level of nuclear
      factor-kappaB (NF-kappaB) activity, which was linked with the suppression of LPS
      induced phosphorylation of p65 at serine 276 and p65 translocation into nuclei,
      but not MAPK signaling. In addition, treatment with EAPS inhibited the production
      of TNF-alpha in LPS-injected mice and suppressed the production of IL-6 and TNF
      alpha in LPS-stimulated splenocytes from BALB/c mice. Therefore, we demonstrate
      here that Patrinia scabiosaefolia potentially inhibits the biomarkers related to
      inflammation through the blocking of NF-kappaB p65 activation, and it may be a
      potential therapeutic candidate for the treatment of inflammatory diseases.

PMID- 21854109
TI  - Assessment of the oxidative stability of conventional and high-oleic sunflower
      oil by means of solid-phase microextraction-gas chromatography.
AB  - Headspace-solid-phase microextraction-gas chromatography (HS-SPME-GC) was used to
      identify in total 74 volatile lipid oxidation compounds altogether in thermally
      stressed conventional and high-oleic sunflower (HOSF) oil samples (in accelerated
      storage conditions for 14 days at 80 degrees C). Out of the volatile compounds
      identified, six volatile compounds were selected as marker compounds for the
      assessment of lipid oxidation of sunflower (SF) and HOSF oils due to their low
      odour threshold values and fatty-rancid odour impression. Additionally, other
      oxidation parameters such as fatty acid composition, peroxide value (PV),
      anisidine value and tocopherol and tocotrienol composition were determined.
      Multivariate statistical methods (principal component analysis and agglomerative
      hierarchical cluster analysis) were applied to identify sensitive oxidation
      marker compounds. Preliminary results revealed that hexanal, E-2-heptenal, E-2
      decenal and E,E-2,4-nonadienal were the most suitable in differentiating HOSF and
      SF oil varieties from each other and SF samples with differing oxidative
      properties. Differentiation of SF samples according to their volatile compound
      composition was done in accordance with the results from the well-known oil
      quality parameters (e.g. PV or fatty acid composition). In conclusion, the
      combination of volatile compound analysis with HS-SPME-GC and multivariate
      statistical methods provides a sensitive tool in differentiating conventional SF
      and HOSF oils by means of volatile lipid oxidation marker compounds.

PMID- 21854110
TI  - Effect of heparin-binding EGF-like growth factor and amphiregulin on the MAP
      kinase-induced production of vascular endothelial growth factor by human
      granulosa cells.
AB  - The function of granulosa cells is regulated by various hormones and growth
      factors. Our aim is to clarify the regulation of vascular endothelial growth
      factor (VEGF) production induced by heparin-binding EGF-like growth factor (HB
      EGF) and amphiregulin (AR) in a human granulosa cell line, KGN. KGN cells were
      cultured and incubated for 24 h with HB-EGF and AR. The levels of VEGF in the
      culture media were measured by an enzyme-linked immunosorbent assay. The
      activation of MAP kinase in KGN cells was detected by Western blot analysis. VEGF
      production was significantly increased by HB-EGF or AR alone in a dose-dependent
      manner, whereas it was decreased by AG1478 or U0126. The MAP kinase activity was
      increased by treatment with HB-EGF or AR. The results suggested that VEGF is
      induced by HB-EGF and AR through mechanisms involving MAP kinase. The increase in
      VEGF may contribute to neovascularization, which in turn would promote various
      ovulation phenomena as well as follicular growth.

PMID- 21854111
TI  - Leptin deficiency and leptin gene mutations in obese children from Pakistan.
AB  - BACKGROUND: Congenital leptin deficiency is a rare human genetic condition
      clinically characterized by hyperphagia and acute weight gain usually during the
      first postnatal year. The worldwide data on this disorder includes only 14 cases
      and four pathogenic mutations have been reported in the leptin gene. STUDY
      OBJECTIVE: The objectives of this study were to measure serum leptin levels in
      obese children and to detect leptin gene mutations in those found to be leptin
      deficient. PATIENTS AND RESULTS: A total of 25 obese children were recruited for
      the study. Leptin deficiency was detected in nine of them. Leptin gene sequencing
      identified mutations in homozygous state in all the leptin deficient children.
      Two cases carried novel mutations (c.481_482delCT and c.104_106delTCA) and each
      of the remaining seven the previously reported frameshift mutation (c.398delG).
      CONCLUSION: The results suggest that leptin deficiency caused by mutations in the
      leptin gene may frequently be seen in obese Pakistani children from Central
      Punjab.

PMID- 21854113
TI  - Efficacy of facial nerve-sparing approach in patients with vestibular
      schwannomas.
AB  - OBJECT: The goal of this article was to show that a combination of facial nerve
      sparing microsurgical resection and Gamma Knife surgery (GKS) for expansion of
      any residual tumor can preserve good facial nerve function in patients with
      recurrent vestibular schwannoma (VS). METHODS: Records of individuals treated by
      a single surgeon with a facial nerve-sparing technique for a VS between 1998 and
      2009 were retrospectively analyzed for tumor recurrence. Of the 383 patients
      treated for VS, 151 underwent microsurgical resection, and 20 (13.2%) of these
      patients required postoperative retreatment for a significant expansion of
      residual tumor after microsurgery. These 20 patients were re-treated with GKS.
      RESULTS: The rate of preservation of good facial nerve function (Grade I or II on
      the House-Brackmann scale) in patients treated with microsurgery for VS was 97%.
      Both subtotal and gross-total resection had excellent facial nerve preservation
      rates (97% vs 96%), although subtotal resection carried a higher risk that
      patients would require retreatment. In patients re-treated with GKS after
      microsurgery, the rate of facial nerve preservation was 95%. CONCLUSIONS: In
      patients with tumors that cannot be managed with radiosurgery alone, a facial
      nerve-sparing resection followed by GKS for any significant regrowth provides
      excellent facial nerve preservation rates.

PMID- 21854114
TI  - Immunoglobulin G4-related hypertrophic pachymeningitis involving cerebral
      parenchyma.
AB  - The authors report a case of IgG4-related hypertrophic pachymeningitis that
      involved cerebral parenchyma. The mass was removed surgically. Histopathological
      studies showed diffuse infiltration of lymphoplasmacytic cells without evidence
      of Langerhans histiocytes or meningothelial cells. Immunoglobulin G4 was strongly
      positive on immunohistochemical staining. The Gd-enhanced lesion deep inside
      brain parenchyma was completely resolved after 3 months of oral corticosteroid
      medication. A nodular type of hypertrophic pachymeningitis that mimics a
      meningioma is rare. Nevertheless, preoperative presumption is very important, and
      immunohistochemical studies for IgG4 may be helpful in the differential
      diagnosis.

PMID- 21854115
TI  - Brain wounds.

PMID- 21854116
TI  - Recruitment by SDF-1alpha of CD34-positive cells involved in sciatic nerve
      regeneration.
AB  - OBJECT: Increased integration of CD34(+) cells in injured nerve significantly
      promotes nerve regeneration, but this effect can be counteracted by limited
      migration and short survival of CD34(+) cells. SDF-1alpha and its receptor
      mediate the recruitment of CD34(+) cells involved in the repair mechanism of
      several neurological diseases. In this study, the authors investigate the
      potentiation of CD34(+) cell recruitment triggered by SDF-1alpha and the
      involvement of CD34(+) cells in peripheral nerve regeneration. METHODS:
      Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the
      left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups:
      Group 1, crush injury (controls); Group 2, crush injury and local application of
      SDF-1alpha recombinant proteins; and Group 3, crush injury and local application
      of SDF-1alpha antibody. Electrophysiological studies and assessment of
      regeneration markers were conducted at 4 weeks after injury; neurobehavioral
      studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of
      SDF-1alpha, accumulation of CD34(+) cells, immune cells, and angiogenesis factors
      in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after
      injury. RESULTS: Application of SDF-1alpha increased the migration of CD34(+)
      cells in vitro, and this effect was dose dependent. Crush injury induced the
      expression of SDF-1alpha, with a peak of 10-14 days postinjury, and this
      increased expression of SDF-1alpha paralleled the deposition of CD34(+) cells,
      expression of VEGF, and expression of neurofilament. These effects were further
      enhanced by the administration of SDF-1alpha recombinant protein and abolished by
      administration of SDF-1alpha antibody. Furthermore, these effects were consistent
      with improvement in measures of neurological function such as sciatic function
      index, electrophysiological parameters, muscle weight, and myelination of
      regenerative nerve. CONCLUSIONS: Expression of SDF-1alpha facilitates recruitment
      of CD34(+) cells in peripheral nerve injury. The increased deposition of CD34(+)
      cells paralleled significant expression of angiogenesis factors and was
      consistent with improvement of neurological function. Utilization of SDF-1alpha
      for enhancing the recruitment of CD34(+) cells involved in peripheral nerve
      regeneration may be considered as an alternative treatment strategy in peripheral
      nerve disorders.

PMID- 21854117
TI  - Bipolar duraplasty: a new technique for reducing transcranial cerebral herniation
      to allow for definitive cranioplasty.
AB  - Large, full-thickness calvarial defects cause increased brain tissue compliance,
      often resulting in transient, transcranial herniation in the setting of
      normotensive intracranial pressures. Cranioplasty serves to protect the cerebrum
      from external injury, provide an aesthetic contour, and alleviate neurological
      symptoms. Traditional options for management include head elevation, osmotic
      diuresis, mild hyperventilation, durotomy with closure following fluid
      evacuation, expansile cranioplasty, lobectomy, and procedure abortion with
      prolonged helmet therapy. Patients treated conservatively with helmet therapy
      commonly are noncompliant and sustain repeated minor trauma to unprotected
      cerebral contents. Furthermore, recent literature suggests that early
      cranioplasty may improve outcomes and reduce costs. The authors present a novel
      solution, bipolar duraplasty, which allows safe, transient reduction of
      normotensive parenchymal herniation using bipolar electrocautery. The dura of the
      herniated sac is cauterized using a low-set, bipolar current in a series of
      sagittal and coronal lines, resulting in immediate contraction and reduction
      allowing for definitive cranioplasty. This new method was used in a patient with
      a 30-cm(2) frontal bone defect following resection of a right falcine atypical
      meningioma. In this scenario, bipolar duraplasty was performed free of
      complication, and the patient has remained asymptomatic and greatly satisfied for
      1 year since the procedure. This technique might facilitate earlier cranioplasty,
      could be applied to a wide range of patients, and may afford better neurological
      outcomes at a reduced cost.

PMID- 21854118
TI  - Multi-institutional evaluation of deep brain stimulation targeting using
      probabilistic connectivity-based thalamic segmentation.
AB  - OBJECT: Due to the lack of internal anatomical detail with traditional MR
      imaging, preoperative stereotactic planning for the treatment of tremor usually
      relies on indirect targeting based on atlas-derived coordinates. The object of
      this study was to preliminarily investigate the role of probabilistic
      tractography-based thalamic segmentation for deep brain stimulation (DBS)
      targeting for the treatment of tremor. METHODS: Six patients undergoing bilateral
      implantation of DBS electrodes in the thalamus for the treatment of upper
      extremity tremor were studied. All patients underwent stereotactic surgical
      implantation using traditional methods (based on indirect targeting methodologies
      and intraoperative macrostimulation findings) that were programmed for optimal
      efficacy, independent of tractography-based segmentations described in this
      report. Connectivity-based thalamic segmentations were derived by identifying
      with which of 7 cortical target regions each thalamic voxel had the highest
      probability of connectivity. The authors retrospectively analyzed the location of
      the optimal contact for treatment of tremor with connectivity-based thalamic
      segmentations. Findings from one institution (David Geffen School of Medicine at
      UCLA) were validated with results from 4 patients at another institution
      (University of Virginia Health System). RESULTS: Of 12 electrodes implanted using
      traditional methodologies, all but one resulted in efficacious tremor control.
      Connectivity-based thalamic segmentation consistently revealed discrete thalamic
      regions having unique connectivity patterns with distinct cortical regions.
      Although the authors initially hypothesized that the most efficacious DBS contact
      for controlling tremor would colocalize with the thalamic region most highly
      connected with the primary motor cortex, they instead found it to highly
      colocalize with those thalamic voxels demonstrating a high probability of
      connectivity with premotor cortex (center-to-center distance: 0.36 +/- 0.55 mm).
      In contrast to the high degree of colocalization with optimal stimulation site,
      the precise localization of the premotor cortex-defined thalamic region relative
      to the anterior and posterior commissures was highly variable. Having defined a
      connectivity-based target for thalamic stimulation in a cohort of patients at
      David Geffen School of Medicine at UCLA, the authors validated findings in 4
      patients (5 electrodes) who underwent surgery at a different institution
      (University of Virginia Health System) by a different surgeon. CONCLUSIONS: This
      report identifies and provides preliminary external validation of a novel means
      of targeting a patient-specific therapeutic thalamic target for the treatment of
      tremor based on individualized analysis of thalamic connectivity patterns. This
      novel thalamic targeting approach is based on identifying the thalamic region
      with the highest probability of connectivity with premotor and supplementary
      motor cortices. This approach may prove to be advantageous over traditional
      preoperative methods of indirect targeting, providing patient-specific targets
      that could improve the precision, efficacy, and efficiency of deep brain
      stimulation surgery. Prospective evaluation and development of methodologies to
      make these analyses more widely available to neurosurgeons are likely warranted.

PMID- 21854119
TI  - C5-8 brachial plexus root injury: the "T-1 hand".
AB  - OBJECT: Classically, C5-7 root injuries of the brachial plexus have been
      associated with palsies of shoulder abduction/external rotation, elbow
      flexion/extension, and wrist, thumb, and finger extension. However, current
      myotome maps generally indicate that C-8 participates in the innervation of thumb
      and finger extensors. Therefore, the authors have hypothesized that, for palsies
      of the thumb and finger extensors, the injury should affect the C-5 through C-8
      roots. METHODS: The authors tested their hypothesis in 30 patients with upper
      type palsies of the brachial plexus. They traced a correlation between clinical
      findings and root injury, as documented by CT myelography, direct visualization
      during surgery, and electrophysiological studies. RESULTS: In C5-8 root injuries,
      shoulder abduction and external rotation were paralyzed, and in all patients,
      wrist extensors were paralyzed. However, in 22 of the 30 patients, wrist
      extension was possible, because of contraction of the extensor digitorum communis
      and extensor pollicis longus. Wrist flexion and pronation also were preserved.
      The T-1 root contributed significantly to innervation of the thumb and finger
      flexors, ensuring 34% grasping and 40% pinch strength relative to the normal
      side. Hand sensation was largely preserved. CONCLUSIONS: Based on the authors'
      observations, they suspect that the clinical scenario previously attributed to a
      C5-7 root injury is, in fact, a C5-8 root injury. The authors propose referring
      to this partial palsy of the brachial plexus as a "T-1 hand."

PMID- 21854120
TI  - A meningioma and its consequences for American history and the rise of
      neurosurgery.
AB  - The case of General Leonard Wood is notable both for its contribution to the
      field of neurosurgery and its historical significance. As one of Harvey Cushing's
      first successful brain tumor operations in 1910, Wood's surgery was part of the
      case series that culminated in Cushing's monograph Meningioma. This case was
      important to the rise of Cushing's career and his recognition as a member of the
      next generation of neurosurgeons who did not settle for mere bony decompression
      to taper intracranial tension but who dared to pursue intradural resections
      operations that had been performed by surgeons for decades but were frowned upon
      because of the attendant risks.   Cushing's operation to remove a recurrent brain
      tumor ended Wood's life in 1927. The authors discuss the effects the tumor may
      have had on Wood's life and career, explore an alternate explanation for the
      cause of Wood's death, and provide a brief account of the life of General Wood,
      highlighting events in his military and administrative career juxtaposed against
      the progression of his illness. Furthermore, the case history of the General is
      reviewed, using information drawn from the original patient notes and recently
      discovered images from the Cushing Brain Tumor Registry that elucidate more
      details about General Wood's story, from the injury that caused his first tumor
      to his final surgery, leading to his demise.

PMID- 21854121
TI  - Low-grade gliomas.

PMID- 21854122
TI  - Facial nerve and acoustic neuromas.

PMID- 21854123
TI  - Maternal factor V Leiden and adverse pregnancy outcome: deciding whether or not
      to test.
AB  - This narrative review examines the translation from statistical association to
      change in clinical practice with respect to factor V Leiden and adverse pregnancy
      outcome. A collation of published meta-analyses illustrates a clear trend towards
      a greater association with factor V Leiden (fVL) as the severity of adverse
      pregnancy outcomes increases, and highlights that different study populations are
      relevant to different clinical scenarios. The yield of fVL testing in women with
      previous adverse pregnancy outcomes is up to six times higher than in the general
      population. Calculated post-test probabilities illustrate that the combined
      effect of fVL and poor pregnancy history places these women at a high-risk of
      recurrent events. The results to date of low molecular weight heparin (LMWH)
      treatment trials cannot be extrapolated to all women with thrombophilia; however,
      the results provide a rationale for randomized prophylactic anticoagulant
      treatment trials in thrombophilic women with severe adverse pregnancy outcomes.
      While we await the results of well-designed, adequately powered treatment trials,
      we propose that post-test probabilities, in addition to the preliminary treatment
      data in high-risk women, justify consideration of screening for fVL in women with
      a strong past history of poor pregnancy outcome.

PMID- 21854124
TI  - Neonatal functional lung maturity relative to gestational age at delivery, fetal
      growth, and pregnancy characteristics in triplet births.
AB  - OBJECTIVE: The purpose of this study was to determine if functional lung maturity
      (FtLM) of triplets was affected by differentiating factors within the triplet
      set. METHODS: This was a retrospective cohort study of triplets. Data were
      collected on maternal, pregnancy and neonatal characteristics and FtLM was
      determined, based on selected neonatal outcomes. RESULTS: Functional lung
      immaturity (FtLI) was found in 35.5% of the infants and occurred in those born
      between 28.1 and 34.6 weeks gestation. Gestational age at delivery, pre-pregnancy
      BMI, and gestational diabetes were predictive of an infant having FtLM; while
      infertility treatment, pre-pregnancy BMI, and preeclampsia were predictors of
      FtLM discordance. CONCLUSIONS: Our results demonstrated FtLI was likely at early
      gestation (<28 weeks) and FtLM was probable beyond 35 weeks. Discordance for FtLM
      was likely at 32 weeks; therefore, clinicians should guard against complacency
      that this gestational mark assures an uncomplicated respiratory course for all
      infants within the set.

PMID- 21854125
TI  - Delineating the receptor mechanisms underlying the rapid vascular contractile
      effects of aldosterone and estradiol.
AB  - It is increasingly appreciated that steroid hormones such as aldosterone and
      estradiol can mediate important cardiovascular effects. Many of these effects
      occur over a time course not consistent with the genomic actions of these
      hormones acting through classical nuclear receptors / transcription factors.
      Further, multiple receptors have been implicated in mediating these rapid effects
      of both aldosterone and estradiol, including a newly appreciated G-protein
      coupled receptor, GPR30. In previous studies we demonstrated that both
      aldosterone and estradiol mediate contraction in vascular smooth muscle cells, as
      assessed in single cell assays. However, the receptor mechanisms underlying these
      effects remained unclear. Therefore, we studied the actions of estradiol and
      aldosterone on rat aortic vascular smooth muscle cells. Both aldosterone and
      estradiol mediated a concentration-dependent increase in contraction, as assessed
      in substrate deformation assays with EC(50)s in the range of nanomoles per litre.
      These effects paralleled increased myosin light chain phosphorylation. The
      effects of aldosterone were inhibited by the mineralocorticoid selective
      antagonist eplerenone. Further, aldosterone's contractile effects were enhanced
      by increased expression of the mineralocorticoid receptor. The contractile
      effects of estradiol were inhibited by estrogen receptor (ER)-selective
      antagonists, tamoxifen, and ICI 182780, as well as eplerenone. Further,
      estradiol's effects were enhanced by the increased expression of both ERalpha and
      the mineralocorticoid receptor (MR). To assess the potential role of GPR30 in
      mediating the effects of aldosterone and estradiol, GPR30 was re-introduced,
      since these cells lose endogenous GPR30 expression in culture. Re-expression of
      GPR30 enhanced both estradiol- and aldosterone-mediated contraction. These
      studies demonstrate that in rat aortic vascular smooth muscle cells, both
      aldosterone and estradiol mediate vascular smooth muscle contraction and that
      these effects can be mediated by MR, ERalpha, and by GPR30.

PMID- 21854126
TI  - The application of a clinical risk stratification score may reduce unnecessary
      investigations for pulmonary embolism in pregnancy.
AB  - OBJECTIVE: To examine the use of the modified Wells score in pregnancy as a risk
      stratification tool in the diagnosis of pulmonary embolism (PE). METHODS: All
      pregnant or post-partum patients who were referred for CT Pulmonary Angiography
      (CTPA) to evaluate suspected PE over a 5-year period were included in the study.
      Patient records were used to apply the modified Wells score (MWS) and analyze
      their risk of PE. RESULTS: A total of 125 women were referred for CTPA over 5
      years. A MWS of 6 or greater ("High Risk") was 100% sensitive and 90% specific
      with a positive predictive value of 36% for PE on CTPA. No patients with a low
      MWS (less than 6) had a PE, giving a negative predictive value of 100%. p<=0.001.
      D-dimers, chest X-ray, blood gases and EKG were significantly less effective than
      the MWS in aiding the diagnosis of PE. CONCLUSION: Current methods employed for
      the diagnosis of PE are inadequate. Risk stratification using the MWS may allow
      safe exclusion of PE before resorting to CTPA. To the best of our knowledge this
      is the first study to have used the MWS in a pregnant patient group.

PMID- 21854128
TI  - An L-2 burst fracture and cauda equina syndrome due to tetanus.
AB  - Thoracic vertebral compression fractures are a known complication of generalized
      tetanus. The authors report the first known case of an L-2 burst fracture leading
      to cauda equina syndrome, as a result of generalized tetanus.   This 51-year-old
      man had generalized tetanus with a constellation of symptoms including
      compartment syndrome requiring fasciotomies, severe axial spasms and spasms of
      the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and
      rhabdomyolysis. During the course of his illness, areflexic paraparesis developed
      in his lower extremities. He was found to have an L-2 burst fracture with
      retropulsion of a bone fragment resulting in cauda equina syndrome. Operative
      intervention was undertaken to decompress the cauda equina and stabilize the
      spine.   The natural progression of tetanus can be complex, with a mixed picture
      ranging from spasms plus increased tone and reflexes to reduced tone and reflexes
      as presynaptic nerve terminals become damaged. The authors suggest that all
      sudden changes in the neurological examination should prompt consideration of
      diagnostic imaging before attributing such changes to natural progression of the
      disease.

PMID- 21854127
TI  - Increase of sensitivity to mechanical stimulus after transplantation of murine
      induced pluripotent stem cell-derived astrocytes in a rat spinal cord injury
      model.
AB  - OBJECT: Clinical use of autologous induced pluripotent stem cells (iPSCs) could
      circumvent immune rejection and bioethical issues associated with embryonic stem
      cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting
      disability, and current therapeutic approaches are not satisfactory. In the
      present study, the authors used the neural stem sphere (NSS) method to
      differentiate iPSCs into astrocytes, which were evaluated after their
      transplantation into injured rat spinal cords. METHODS: Induced pluripotent stem
      cell-derived astrocytes were differentiated using the NSS method and injected 3
      and 7 days after spinal contusion-based SCI. Control rats were injected with DMEM
      in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and
      locomotion tests were evaluated at 8 weeks. Immunohistological parameters were
      then assessed. RESULTS: Transplant recipients lived for 8 weeks without tumor
      formation. Transplanted cells stretched their processes along the longitudinal
      axis, but they did not merge with the processes of host GFAP-positive astrocytes.
      Locomotion was assessed in 3 ways, but none of the tests detected statistically
      significant improvements compared with DMEM-treated control rats after 8 weeks.
      Rather, iPSC transplantation caused even greater sensitivity to mechanical
      stimulus than DMEM treatment. CONCLUSIONS: Astrocytes can be generated by serum
      treatment of NSS-generated cells derived from iPSCs. However, transplantation of
      such cells is poorly suited for repairing SCI.

PMID- 21854129
TI  - Spinal cord injury and pain.

PMID- 21854130
TI  - Congenital atlantoaxial dislocation: a dynamic process and role of facets in
      irreducibility.
AB  - OBJECT: Patient age at presentation with congenital atlantoaxial dislocation
      (CAAD) is variable. In addition, the factors determining irreducibility or
      reducibility in these patients remain unclear. The facets appear to contribute to
      the stability of the joint, albeit to an unknown extent. The objective of this
      paper was to study the characteristics of C1-2 facets in these patients and their
      bearing on the clinicoradiological presentation and management. METHODS: Twenty
      four patients with CAAD were studied. Fifteen patients had irreducible CAAD
      (IrAAD); 3 of these patients experienced incomplete reduction after traction, and
      9 had reducible CAAD (RAAD). The images (CT scans of the craniovertebral junction
      in a neutral position) obtained in the parasagittal, axial, and coronal planes
      were studied with respect to the C1-2 facets and were compared with 32 control
      scans. The inferior sagittal and coronal C-1 facet angles were measured. The
      lordosis of the cervical spine (cervical spine angle calculated on radiographs of
      the cervical spine, neutral view) in these patients was compared with normal. The
      management of these patients is described. RESULTS: The inferior sagittal C-1
      facet angle and at least one coronal angle in patients with IrAAD were
      significantly acute compared with those in patients with RAAD and the control
      population. A significant correlation was found between age and the acuteness of
      the inferior sagittal C-1 facet angle (that is, the more acute the angle, the
      earlier the presentation). The lordosis of the cervical spine was exaggerated in
      patients with IrAAD. Three patients with IrAAD who had smaller acute angles
      experienced a partial reduction after traction and a complete reduction after
      intraoperative distraction of the facets, thereby avoiding a transoral procedure.
      An inferior sagittal C-1 facet angle of more than 150 degrees  in the sagittal
      plane predicted reducibility. Drilling a wedge off the facet in the sagittal
      plane to make the inferior sagittal C-1 facet angle 150 degrees  can reduce the
      C1-2 joint intraoperatively by posterior approach alone. CONCLUSIONS: The
      acuteness of the inferior C-1 sagittal facet angles possibly determines the age
      at presentation and reducibility. The coronal angles determine the telescoping of
      C-2 within C-1. Patients with IrAAD can be treated using a posterior approach
      alone with the exception of those with extremely acute angles or a retroflexed
      dens. The exaggerated lordosis of the cervical spine in these patients is a
      compensatory phenomenon.

PMID- 21854131
TI  - Weight-depression association in a high-risk maternal population.
AB  - OBJECTIVE: Both maternal depression and overweight carry potential adverse
      effects on perinatal health and are inter-related. We explored the relationship
      between weight and depressive symptoms in a high-risk maternal population.
      METHODS: We administered the Edinburgh Postnatal Depression Scale (EPDS) to all
      women attending the Motherisk Clinic at The Hospital for Sick Children between
      October 2007 and April 2010. We explored possible associations between the EPDS
      scores, maternal weight and other characteristics. RESULTS: The study population
      consisted of 352 women, 43.7% of whom were pregnant, with a variety of exposures.
      Twenty seven percent of the study population had diagnosed depression. Depressed
      women had a significantly higher body weight compared to non-depressed women (p =
      0.016). The same finding remained significant in the pregnant sub-group. The EPDS
      score, for the entire study population, was significantly correlated with body
      weight (p = 0.027). Use of antidepressants was an independent predictor of
      maternal weight in a multivariate regression analysis. CONCLUSIONS: There is a
      strong association between maternal weight and depressive symptoms, whether
      diagnosed or not. Antidepressant therapy is an independent predictor of maternal
      weight. Since both depression and maternal overweight may adversely affect
      pregnancy outcome, and are treatable, addressing both is essential for optimal
      pregnancy management.

PMID- 21854132
TI  - Comparative efficacy of probiotic yoghurt and clindamycin in treatment of
      bacterial vaginosis in pregnant women: a randomized clinical trial.
AB  - OBJECTIVE: This study was performed to determine the comparative efficacy of
      probiotic yoghurt and clindamycin in the treatment of bacterial vaginosis in
      pregnant women in the third trimester. METHODS AND MATERIALS: This randomized
      clinical trial was performed as an open-label study. 310 symptomatic patients
      with BV were recruited. Diagnosis of BV was through Amsel criteria. The patients
      were randomly assigned to receive either probiotic yoghurt (100 g twice a
      day/week) or orally administered clindamycin (300 mg twice a day/week). RESULTS:
      Ten patients in probiotic group and 9 subjects in clindamycin group had symptom
      recurrence (p > 0.05). 132 patients in probiotic group and 105 subjects in
      clindamycin group had pH decrease (p < 0.0001). 140 patients in probiotic group
      and 141 subjects in clindamycin group had complete symptomatic cure (p > 0.05).
      Twelve patients in probiotic group and seven subjects in clindamycin group had
      preterm birth. Nine women in probiotic group and five subjects in clindamycin
      group had PROM (p > 0.05). CONCLUSIONS: According to the obtained results, it may
      be concluded that probiotics would have a good efficacy in the treatment of
      bacterial vaginosis in pregnancy leading to decreased burden of subsequent
      preterm birth.

PMID- 21854133
TI  - Severe maternal morbidity in a tertiary care centre of northern Italy: a 5-year
      review.
AB  - OBJECTIVE: To assess prevalence and causes of severe acute maternal morbidity
      cases and evaluate their impact on feto-maternal wellbeing and on facility
      resources. STUDY DESIGN: Observational retrospective study adopting management
      based criteria in a tertiary care public hospital during a 5-year period.
      Criteria adopted were: intensive care unit admission, blood transfusion >= 4
      units, emergency peripartum hysterectomy and arterial embolization at any time
      during pregnancy. RESULTS: A total of 80 cases were identified, most of them
      (97.5%) through a combination of two criteria, ICU admission and blood
      transfusion. Commonest severe obstetric morbidities were major obstetric
      haemorrhage (48.8%) and hypertensive disorders (27.5%). Immigrant status (OR
      1.68, 95% CI 1.03-2.7), pre-term birth (OR 4.15, 95% CI 2.5-6.8), Caesarean
      section (OR 7.74,95% CI 4.2-14.3) were factors significantly associated with SAMM
      cases. Major abdominal surgery was necessary in 26 women (32.5%), with emergency
      peripartum hysterectomy in 11 (13.5%). These events led to an average blood
      consumption per woman of 6.5 +/- 12.8 units and a mean hospital stay of 8.9 +/-
      5.0 days, significantly longer (p < 0.001) than the average duration of post
      delivery care. Maternal mortality to morbidity ratio was 1:80. CONCLUSIONS: An
      integrated intervention-based approach proved to be effective in finding severe
      acute maternal morbidity cases. Information on underlying causes and associated
      risk factors may improve prevention and treatment of obstetric morbidities, thus
      reducing feto-maternal adverse effects and hospital expenditures.

PMID- 21854134
TI  - Recurrent preterm birth in women treated with 17 alpha-hydroxyprogesterone
      caproate: the contribution of risk factors in the penultimate pregnancy.
AB  - OBJECTIVE: Examine rates of recurrent, spontaneous preterm birth (PTB) in women
      treated prophylactically with 17 alpha-hydroxyprogesterone caproate (17P) when
      the penultimate PTB was due to preterm labor (PTL) or preterm premature rupture
      of the membranes (pPROM). METHODS: Retrospective, descriptive, database study of
      1183 singleton gestations that initiated prophylactic 17P at <21 weeks with a
      penultimate PTB. Primary outcomes examined were rates of recurrent PTB at <37 and
      <32 weeks' gestation in the PTL (n = 939) and pPROM (n = 244) cohorts. RESULTS:
      Recurrent PTB <37 weeks occurred in 38% versus 28.3% of the PTL and pPROM
      cohorts, respectively (p <0.005). Rates of recurrent PTB <32 weeks were similar.
      Logistic regression revealed three risk factors increased the odds of recurrent
      PTB: >1 previous PTB (OR 1.8 [95% CI: 1.33-2.44]); penultimate birth at 28-33.9
      weeks' gestation (OR 1.61 [95% CI: 1.22-2.13]); and, PTL as the indication for
      delivery in the penultimate PTB (OR 1.66 [95% CI: 1.16-2.37]). CONCLUSION:
      Several historical factors increase the risk for recurrent PTB in women receiving
      17P. Contrary to earlier studies of PTL and pPROM recurrence, women receiving
      prophylactic 17P with a penultimate PTB due to pPROM are at lower risk of
      recurrent PTB than those with a history of PTL.

PMID- 21854135
TI  - Quality assurance of nuchal translucency for prenatal fetal Down syndrome
      screening.
AB  - OBJECTIVE: To assess the quality of nuchal translucency, (NT) measurements were
      performed at four public institutions performing routine first trimester combined
      prenatal screening for Down syndrome. METHODS: The median of the NT-MoM
      distribution and standard deviation (SD) of the log(10) NT-MoM were determined.
      Sonographers and screening centres distributions were assessed for measures of
      central tendency (median) and dispersion (log(10) SD). Cumulative Sum (CUSUM)
      charts were created to assess whether screening centres and individual
      sonographers who had performed at least 30 NT measurements exhibited any
      systematic bias by checking whether their CUSUM scores exceeded predefined upper
      and lower control limits. RESULTS: Of the 36 sonographers, only 67% (n = 24) had
      performed 30 or more scans. The median NT-MOM at each screening centre ranged
      from 1.02 to 1.09. Screening centre standard deviations ranged from 0.073 to
      0.099. CUSUM charts indicated that only one screening centre remained within the
      predefined control limits throughout the assessment period. Analysis of variance
      indicated that a statistically significant difference existed between the log NT
      MoM distributions of the individual sonographers (F = 10.7; p <0.0001).
      Inspection of the individual sonographer CUSUM charts indicated that 11 (45%) of
      the 24, with more than 30 NT measurements were either under or over measuring the
      NT. CONCLUSION: Prospective monitoring and feedback of quality assurance
      assessment results of sonographers and screening centres should be routinely
      reported as both are responsible, if equity of screening performance is to be
      maintained.

PMID- 21854136
TI  - Optimum mode of delivery in gestations complicated by preterm premature rupture
      of the membranes.
AB  - OBJECTIVES: To provide evidence about the preferable mode of delivery, vaginal
      (VD) or caesarean section (CS), in PPROM. METHODS: A retrospective study of 190
      cases. Survival analysis was used to identify statistically significant
      differences in mortality rates. RESULTS: A total of 126 pregnancies were included
      in our study. Mean gestational age of rupture was 28(+0) weeks (min = 15, max =
      36(+4), sd = 5.796). Mean birth age was 30(+0) weeks (min = 15, max = 37(+2), sd
      = 5.353). CS was performed in 55 cases (43.7%), VD in 71 cases (56.3%). Data
      analysis showed that, regardless of presentation, there was a statistically
      significant benefit on survival in favor of the CS in births below 30 gestational
      weeks (n = 39, nCS = 18, nND = 21, chi(2) = 7.946, p = 0.005). Hazard ratio
      estimation set the critical gestational age at 28 weeks. For vaginal deliveries,
      breech presentation was associated with inferior survival outcome compared to
      vertex (nTotal = 71; nVertex = 63, nBreech = 8, chi(2) = 13.012, p < 0.001.Also
      in breech presentation, VD survival outcome was inferior to CS (nTotal = 9; nVD =
      6, nCS = 3, chi(2) = 5.145, p < 0.05). CONCLUSIONS: According to our results, in
      cases of PPROM, CS was beneficial below 28 weeks and in breech presentation below
      30 weeks.

PMID- 21854137
TI  - Bacterial vaginosis and biomarkers of oxidative stress in amniotic fluid.
AB  - OBJECTIVE: In this study we tried to determine if the activities of the primary
      antioxidant enzymes are detectable in amniotic fluid and if they can be used as
      early biomarkers of complications in pregnancy connected with bacterial
      vaginosis. METHODS: This was a prospective study in which amniotic fluid was
      taken between 16 and 19 weeks of gestation. 161 pregnant women were divided into
      two groups: study group--patients with the treated local infection and control
      group--healthy pregnant women. Levels of reduced glutathione, and the activities
      of glutathione peroxidase, glutathione reductase, glutathione S-transferase,
      xanthine oxidase, superoxide dismutase and lipid peroxidation were determined
      spectrophotometrically in amniotic fluid samples. RESULTS: Concentration of
      malonyldialdehide (product of lipid peroxidation) varied greatly between
      investigated groups. Xanthine oxidase and superoxide dismutase activities, though
      very low, were present in amniotic fluid samples. Also, enzymes of glutathione
      cycle and reduced glutathione concentrations were detectable and showed certain
      variations. CONCLUSION: Although, biomarkers of antioxidant activity are present
      in the amniotic fluid, they are not different between women with and without
      bacterial vaginosis.

PMID- 21854138
TI  - Is routine abdominal ultrasonography necessary in macrosomic newborns with
      difficult delivery?
AB  - Adrenal hemorrhage is a relatively uncommon clinical problem of the newborn
      period. Clinical features of adrenal hemorrhage are variable. An abdominal mass,
      anemia, unexplained/persistent jaundice, bluish discoloration of the scrotum may
      be the presenting sign. Here, we presented a macrosomic infant (4150 gr) whose
      left side adrenal hematoma associated with asphyxia and early onset of
      hyperbilirubinemia. We concluded that the pediatricians should be considered
      abdominal US screening regard as internal hemorrhage in macrosomic newborns who
      delivered with difficult labor and then seen pathologic jaundice.

PMID- 21854139
TI  - The evaluation of learner outcomes in interprofessional continuing education: a
      literature review and an analysis of survey instruments.
AB  - BACKGROUND: Interprofessional education (IPE) is thought to be important in
      fostering interprofessional practice (IPP) and in optimizing patient care, but
      formal evaluation is lacking. AIM: To identify, through review of IPE evaluation
      instruments in the context of Barr/Kirkpatrick's hierarchy of IPE learner
      outcomes, the comprehensiveness of current evaluation strategies and gaps needing
      to be addressed. METHODS: MEDLINE and CINAHL were searched for work relating to
      IPE/IPP evaluation published between 1999 and September 2010 that contained
      evaluation tools. Tool items were stratified by learner outcome. Trends and gaps
      in tool use and scope were evaluated. RESULTS: One hundred and sixty three
      articles were reviewed and 33 relevant tools collected. Twenty-six (78.8%) were
      used in only one paper each. Five hundred and thirty eight relevant items were
      identified, with 68.0% assessing changes in perceptions of IPE/IPP. Fewer items
      were found to assess learner reactions (20.6%), changes in behaviour (9.7%),
      changes in knowledge (1.3%) and organizational practice (0.004%). No items
      addressed benefits to patients; most were subjective and could not be used to
      assess such higher level outcomes. CONCLUSIONS: No gold-standard tool has been
      agreed upon in the literature, and none fully addresses all IPE learner outcomes.
      Objective measures of higher level outcomes are necessary to ensure comprehensive
      evaluation of IPE/IPP.

PMID- 21854140
TI  - Doctors-to-be at the doorstep - comparing service-learning programs in an Asian
      medical school.
AB  - BACKGROUND: Service-learning is a powerful, but underutilized, educational tool
      in Asian medical schools. AIM: We compared the ability of two programs providing
      medical care to low-income populations (clinic-based versus home-based approach)
      to teach community medicine skills in an Asian medical school. METHODS: We
      conducted a cross-sectional study using a self-administered anonymized
      questionnaire on medical students who participated in the programs using the Fund
      for the-Improvement of Postsecondary Education Survey Instrument. Participants
      also gave an overall score for their learning experience in the programs.
      RESULTS: Participation rates were 97.4% (760/780) and 95.8% (230/240) across the
      two programs. A majority of participants in either program felt that the
      experience helped them to improve in all domains surveyed. Regardless of whether
      one compared those who participated in either program or both programs, the home
      based approach was superior at teaching communication skills, teamwork,
      identifying social issues, gaining knowledge, and applying knowledge. Improved
      knowledge on long-term management of chronic diseases (beta = 1.25, 95% CI, 0.55
      1.96) was strongly associated with the overall score for those participating in
      the home-based program. CONCLUSIONS: Service-learning programs, in the Asian
      context, have potential educational value for medical students in a wide range of
      domains. The home-based approach is superior at teaching certain aspects of
      community care.

PMID- 21854141
TI  - Clinical supervisor evaluations during general surgery clerkships.
AB  - BACKGROUND: Clerkship performance is commonly evaluated by consultant surgeons
      who seldom supervise medical students directly. In contrast, surgical residents
      and interns frequently supervise students and provide essential teaching but are
      not tasked with evaluating them. AIM: To prospectively investigate and compare
      the accuracy of general surgery clerkship performance evaluations by clinical
      supervisors of differing seniorities. METHOD: Between September 2008 and May
      2010, clinical supervisors of varying seniorities independently evaluated 57
      fourth-year medical students using a multi-dimensional performance evaluation
      tool. Total evaluation grades and subtotal grades for clinical ability were
      correlated to the results of a validated surgical objective structured clinical
      examination (OSCE). RESULTS: In this study, 85 clinical supervisors provided 427
      student performance evaluations. Total evaluation grades awarded by consultant
      surgeons had weak correlation to student OSCE results (r = 0.27, p < 0.05) and
      associated subtotal grades for clinical ability had no correlation. In
      comparison, the equivalent sets of grades awarded by residents and interns had
      moderate correlations to OSCE results (r = 0.49 and r = 0.54, p < 0.01).
      CONCLUSIONS: Validity of clinical supervisor evaluations during general surgery
      clerkships vary according to assessor seniority. Including performance evaluation
      grades by surgical residents and interns may enhance the overall validity of this
      common clerkship evaluation tool and improve its summative and formative
      assessment value.

PMID- 21854143
TI  - Medical students on the stage: an experimental performative method for the
      development of relational skills.
AB  - BACKGROUND: Development of therapeutic relational skills is a relatively
      neglected area of medical education. Conventional teaching techniques are mostly
      unsuitable for the realization of experience-based learning. AIMS: To develop a
      training method which enables lived self-experiences of the therapeutic
      relationship in class. To help students understand that illness and the doctor
      patient relationship are integrated in the network of life histories and other
      relationships. METHODS: Our Integrated Performative Action Method is based on the
      elaboration of a short story of an illness in a student group. Through the 5
      phases of the process, students write their own version of the story, build up
      characters, scenarios and enact the play. We have tested the method with 6 groups
      of students (n = 70) in a 10-week course. Video-recordings and minutes of
      sessions were analysed by two independent observers. RESULTS: Through elaborating
      the characters and playing the roles, students could speak about their own
      problems and act out feelings in the name of the characters. All groups had
      strong involvement throughout the process. CONCLUSIONS: The method helps to
      experience the ways in which therapeutic relationships and professional
      identities are constructed, reflected upon and communicated in a group of medical
      students.

PMID- 21854142
TI  - Predictive validity of the personal qualities assessment for selection of medical
      students in Scotland.
AB  - BACKGROUND: The Personal Qualities Assessment (PQA) was developed to enhance
      medical student selection by measuring a range of non-cognitive attributes in the
      applicants to medical school. Applicants to the five Scottish medical schools
      were invited to pilot the test in 2001 and 2002. AIMS: To evaluate the predictive
      validity of PQA for selecting medical students. METHODS: A longitudinal cohort
      study was conducted in which PQA scores were compared with senior year medical
      school performance. RESULTS: Consent to access performance markers was obtained
      from 626 students (61.6% of 1017 entrants in 2002-2003). Linkable Foundation Year
      (4th) rankings were available for 411 (66%) students and objective structured
      clinical examination (OSCE) rankings for 335 (54%) of those consenting. Both
      samples were representative of the original cohort. No significant correlations
      were detected between separate elements of the PQA assessment and student
      performance. However, using the algorithm advocated by Powis et al. those defined
      as 'non-extreme' (<+/-1.5 SD from the cohort mean scores; SD, standard deviation)
      character types on the involved-detached and on the libertarian-communitarian
      moral orientation scales were ranked higher in OSCEs (average of 7.5% or 25 out
      of 335, p = 0.049). CONCLUSIONS: This study was limited by high attrition and
      basic outcome markers which are insensitive to relevant non-cognitive
      characteristics. However, it is the largest currently available study of
      predictive validity for the PQA assessment. There was one finding of
      significance: that those students who were identified by PQA as 'not extreme' on
      the two personal characteristics scales performed better in an OSCE measure of
      professionalism. Futures studies are required since psychometric testing for both
      cognitive and non-cognitive attributes are increasingly used in admission process
      and these should include more and better measures of professionalism against
      which to correlate non-cognitive traits.

PMID- 21854144
TI  - The impact on medical practice of commitments to change following CME lectures: a
      randomized controlled trial.
AB  - BACKGROUND: Self-reported commitment to change (CTC) could be a potentially
      valuable method to address the need for continuing medical education (CME) to
      demonstrate clinical outcomes. AIM: This study determines: (1) are clinicians who
      make CTCs more likely to report changes in their medical practices and (2) do
      these changes persist over time? METHODS: Intervention participants (N = 80)
      selected up to three commitments from a predefined list following the lecture,
      while control participants (N = 64) generated up to three commitments at 7 days
      post-lecture. At 7 and 30 days post-lecture, participants were queried if any
      practice change occurred as a result of attending the lecture. RESULTS: About 91%
      of the intervention group reported practice changes consistent with their
      commitments at 7 days. Only 32% in the control group reported changes (z = 7.32,
      p < 0.001). At 30 days, more participants in the intervention group relative to
      the control group reported change (58% vs. 22%, z = 3.74, p < 0.01). Once a
      participant from either group made a commitment, there were no differences in
      reported changes (63% vs. 67%, z = <0.00, p = 0.38). CONCLUSION: Integration of
      CTC is an effective method of reinforcing learning and measuring outcomes.

PMID- 21854145
TI  - Unprofessional behaviour in medical students: a questionnaire-based pilot study
      comparing perceptions of the public with medical students and doctors.
AB  - BACKGROUND: Evidence suggests that doctors and medical students use different
      strategies to evaluate unprofessional behaviour. Anecdotal evidence suggests that
      the public and profession may judge misdemeanours differently. AIMS: To explore
      whether members of the public will judge examples of medical student misconduct
      more harshly than medical students and doctors. METHODS: This was a pilot cross
      sectional survey of the public, medical students and doctors. For 10 hypothetical
      examples of medical student misconduct and one of appropriate conduct in a
      questionnaire, participants were asked to (1) indicate the level of acceptability
      and (2) to choose the sanction they considered most appropriate for each.
      RESULTS: Overall, doctors were harsher than students and the public were harsher
      than doctors in their choice of sanctions. The most lenient outcomes were
      selected by students for deception in an examination, nonattendance and
      dishonesty. The most punitive were chosen by the public for forgery, criminal
      conviction, misrepresenting qualifications, alcohol and drug misuse and lack of
      insight. CONCLUSIONS: The public judge misdemeanours among medical students more
      harshly than do medical students and medical professionals. This implies that
      views of lay members should be sought by medical schools when promoting
      professionalism and considering cases of medical student misconduct.

PMID- 21854146
TI  - Is running a problem-based learning curriculum more expensive than a traditional
      Subject-Based Curriculum?
AB  - BACKGROUND: Running a problem-based learning (PBL) curriculum has been considered
      to be more expensive than a traditional Subject-Based Curriculum? This claim has
      not been well substantiated. AIM: To identify faculty educational activities
      (FEA) related to PBL, calculate its cost (faculty number and time) and compare it
      with a traditional Subject-Based Curriculum. METHODS: A structured questionnaire
      was developed through focused group discussion using a Delphi method to identify
      FEA and ensure face and content validity. For cost comparison, a hypothetic model
      was developed based on "what if" the curriculum was traditional subject-based,
      and running within the frame of the current regulations of University of Sharjah.
      RESULTS: A total of 23 faculty (16 full-time basic medical sciences and 7
      clinical tutors) equal to 19.5 full-time equivalent (FTE) responded to the
      questionnaire. About five major domains and 26 sub-domains of FEA were
      identified. The calculated number of faculty needed for the hypothetical Subject
      Based Curriculum should have been 19 FTEs. The average FEA hours per faculty per
      week per student in PBL was 17.41 and for the Subject-Based Curriculum would have
      been 17.85. CONCLUSION: PBL does not require an increase in number of faculty.
      The time spent by faculty on educational activities was similar in the two
      curriculum models. Although the cost of two strategies was similar, but the
      educational roles and the faculty engagement in education in a PBL curriculum is
      broader than in the traditional curriculum.

PMID- 21854147
TI  - 'The research compass': an introduction to research in medical education: AMEE
      Guide no. 56.
AB  - This AMEE Guide offers an introduction to research in medical education. It is
      intended for those who are contemplating conducting research in medical education
      but are new to the field. The Guide is structured around the process of
      transforming ideas and problems into researchable questions, choosing a research
      approach that is appropriate to the purpose of the study and considering the
      individual researcher's preferences and the contextual possibilities and
      constraints. The first section of the Guide addresses the rationale for research
      in medical education and some of the challenges posed by the complexity of the
      field. Next is a section on how to move from an idea or problem to a research
      question by placing a concrete idea or problem within a conceptual, theoretical
      framework. The following sections are structured around an overview model of
      approaches to medical education research, 'The research compass'. Core to the
      model is the conceptual, theoretical framework that is the key to any direction.
      The compass depicts four main categories of research approaches that can be
      applied when studying medical education phenomena, 'Explorative studies';
      'Experimental studies'; 'Observational studies'; and 'Translational studies'.
      Future AMEE Guides in the research series will address these approaches in more
      detail.

PMID- 21854148
TI  - Twelve tips for conducting collaborative research in medical education.
AB  - BACKGROUND: Developing and ensuring successful collaborative research in medical
      education is no small task, but the rewards to researchers can be great.
      Collaborative research in medical education offers significant opportunities for
      investigators who wish to pool limited resources and expand professional
      networks. Despite this, collaboration often occurs without advance planning for
      the logistical aspects of collaborative work. AIMS AND METHODS: These 12 tips,
      derived from developing and presenting a session on strategies for effective
      collaboration conducted at a national meeting, will assist readers who are
      planning to collaborate or are already engaged in collaborative scholarship. The
      tips are organized into items to consider in three phases of collaboration:
      planning, implementation, and dissemination of outcomes. RESULTS AND CONCLUSIONS:
      From selecting a topic to recognizing when the collaboration should end, the tips
      underscore the importance of good communication, and clear expectations for
      participants.

PMID- 21854149
TI  - Using bibliographic software to appraise and code data in educational systematic
      review research.
AB  - BACKGROUND: Bibliographic database software is often recommended as a tool that
      can assist researchers in managing the large numbers of references produced in
      early stages of a systematic review. The uses of such software in systematic
      review research are often represented solely in terms of bibliographic functions,
      while the uses that extend beyond simple bibliographic functions have not been
      explored. AIMS: This article provides a guide on how to use extended functions of
      bibliographic software to systematically complete the steps of appraising search
      results and coding references for inclusion in or exclusion from the systematic
      review. METHODS: The process is illustrated using an ongoing systematic review as
      a case description and using screenshots from the bibliographic database,
      EndNote(r), the authors' preferred software program for the study. RESULTS: The
      case description illustrates how bibliographic software serves not only to
      organize and store search results, but also to appraise and code search results
      and to explicitly track researchers' decisions across the systematic review.
      CONCLUSION: Bibliographic tools can contribute to make the methods that
      researchers adopt for the phase following the initial literature search more
      transparent and systematic. The illustrative case description involves a
      systematic review of academic education in occupational therapy, but easily
      generalizes to systematic reviews in other health science professions.

PMID- 21854150
TI  - A comparison of answer retrieval through four evidence-based textbooks (ACP PIER,
      Essential Evidence Plus, First Consult, and UpToDate): a randomized controlled
      trial.
AB  - BACKGROUND: The efficacy of bedside information products has not been properly
      evaluated, particularly in developing countries. AIM: To compare four evidence
      based textbooks by comparing efficacy of their use by clinical residents, as
      measured by the proportion of questions for which relevant answers could be
      obtained within 20 min, the time to reach the answer and user satisfaction.
      METHODS: One hundred and twelve residents were taught information mastery basics
      and were randomly allocated to four groups to use: (1) ACP PIER, (2) Essential
      Evidence Plus (formerly InfoRetriever), (3) First Consult, and (4) UpToDate.
      Participants received 3 of 24 questions randomly to retrieve the answers from the
      assigned textbook. Retrieved answers and time-to-answers were recorded by special
      designed software, and the researchers determined if each recorded answer was
      relevant. RESULTS: The rate of answer retrieval was 86% in UpToDate, 69% in First
      Consult, 49% in ACP PIER, and 45% in Essential Evidence Plus (p < 0.001). The
      mean time-to-answer was 14.6 min using UpToDate, 15.9 min using First Consult,
      16.3 min using Essential Evidence Plus, and 17.3 min using ACP PIER (p < 0.001).
      CONCLUSION: UpToDate seems more comprehensive in content and also faster than the
      other three evidence-based textbooks. Thus, it may be considered as one of the
      best sources for answering clinicians' questions at the point of care.

PMID- 21854151
TI  - Providing feedback: exploring a model (emotion, content, outcomes) for
      facilitating multisource feedback.
AB  - BACKGROUND: Multi-source feedback (MSF) aims to raise self-awareness of
      performance and encourage improvement. The ECO model (emotions, content, outcome)
      is a three-step process developed from the counselling literature to facilitate
      feedback acceptance and use in MSF. AIMS: The purpose of this study was to
      explore the acceptability, usefulness and educational impact of the model.
      METHODS: This was a qualitative study using interviews to explore general
      practice (GP) trainer and trainee experiences and perceptions of the ECO
      facilitation model. Interviews were conducted by telephone, recorded, transcribed
      and analysed using a thematic framework. RESULTS: About 13 GP trainers and
      trainees participated in the interviews following their MSF discussions using the
      ECO model. They agreed that the model was useful, simple to use and engaged
      trainees in reflection upon their feedback and performance. Exploring emotions
      and clarifying content appeared integral to accepting and using the feedback.
      Positive feedback was often surprising. Most trainees reported performance
      improvements following their MSF-ECO session. CONCLUSIONS: The model appeared
      acceptable and simple to use. Engaging the learner as a partner in the feedback
      discussion appeared effective. Further research is needed to fully understand the
      influence of each step in facilitating MSF acceptance and use, and to determine
      the impact of the ECO model alone upon performance outcomes compared to more
      traditional provision of MSF feedback.

PMID- 21854152
TI  - My reflection on 30 years of teaching medical students, residents and faculty.

PMID- 21854153
TI  - The problems program directors inherit: medical student distress at the time of
      graduation.
AB  - BACKGROUND: Distress is prevalent among residents and often attributed to rigors
      of training. AIMS: To explore the prevalence of burnout and depression and
      measured mental quality of life (QOL) among graduating medical students shortly
      before they began residency. METHOD: Pooled analysis of data from 1428 fourth
      year medical students who responded to 1 of 3 multi-institutional studies.
      Students completed the Maslach Burnout Inventory, PRIME MD, and SF-8 to measure
      burnout, depression, and low mental QOL (defined as mean mental SF-8 scores 1/2 a
      standard deviation below the population norm) and answered demographic items.
      RESULTS: Shortly before beginning residency, 49% of responding medical students
      had burnout, 38% endorsed depressive symptoms, and 34% had low mental QOL. While
      no differences in the prevalence of distress was observed by residency specialty
      area, there were subtle differences in the manifestation of burnout by specialty.
      Medical students entering surgical fields had lower mean emotional scores,
      students entering primary care fields had lower mean depersonalization scores,
      and students entering non-primary care/non-surgical fields reported the lowest
      mean personal accomplishment scores (all p <= 0.03). CONCLUSION: Our results
      indicate a high prevalence of distress among graduating medical students across
      all specialty disciplines before they even begin residency training.

PMID- 21854154
TI  - Student Selected Components (SSCs): Guide supplement 46.1 - viewpoint.

PMID- 21854155
TI  - Using rural and remote settings in the undergraduate medical curriculum: Guide
      supplement 47.1 - viewpoint.

PMID- 21854156
TI  - The use of (silent) mannequins to teach communication skills to medical students:
      an experimental approach in Italy.

PMID- 21854159
TI  - Step-based translation of physical activity guidelines in the Lower Mississippi
      Delta.
AB  - To determine how many steps.day(-1) equate to current moderate-to-vigorous
      physical activity (MVPA) guidelines in a population from the Lower Mississippi
      Delta (LMD) of the United States, 58 overweight adults wore an Actigraph
      accelerometer (GT3X) for up to 2 weeks. Min.day(-1) in MVPA was a good predictor
      of steps.day(-1) (r(2) = 0.62; p < 0.001; linear regression), such that 30 min of
      daily MVPA equated to 9154 steps.day(-1) (mixed-model approach). Using receiver
      operating characteristic analysis, sensitivity and specificity were optimized at
      8357 steps.day(-1). Results indicate that overweight residents of the LMD should
      be accumulating at least 8300-9100 steps.day(-1) to meet the recommendation of 30
      min.day(-1) MVPA.

PMID- 21854160
TI  - Prevalence of caffeine use in elite athletes following its removal from the World
      Anti-Doping Agency list of banned substances.
AB  - The aim of this investigation was to determine the use of caffeine by athletes
      after its removal from the World Anti-Doping Agency list. For this purpose, we
      measured the caffeine concentration in 20 686 urine samples obtained for doping
      control from 2004 to 2008. We utilized only urine samples obtained after official
      national and international competitions. Urine caffeine concentration was
      determined using alkaline extraction followed by gas chromatography-mass
      spectrometry. The limit of detection (LOD) was set at 0.1 ug.mL(-1). The
      percentage of urine samples below the LOD was 26.2%; the remaining 73.8% of the
      urine samples contained caffeine. Most urine samples (67.3%) had urinary caffeine
      concentrations below 5 ug.mL(-1). Only 0.6% of urine samples exceeded the former
      threshold for caffeine doping (12 ug.mL(-1)). Triathlon (3.3 +/- 2.2 ug.mL(-1)),
      cycling (2.6 +/- 2.0 ug.mL(-1)), and rowing (1.9 +/- 1.4 ug.mL(-1)) were the
      sports with the highest levels of urine caffeine concentration; gymnastics was
      the sport with the lowest urine caffeine concentration (0.5 +/- 0.4 ug.mL(-1)).
      Older competitors (>30 y) had higher levels of caffeine in their urine than
      younger competitors (<20 y; p < 0.05); there were no differences between males
      and females. In conclusion, 3 out of 4 athletes had consumed caffeine before or
      during sports competition. Nevertheless, only a small proportion of these
      competitors (0.6%) had a urine caffeine concentration higher than 12 ug.mL(-1).
      Endurance sports were the disciplines showing the highest urine caffeine
      excretion after competition.

PMID- 21854161
TI  - Consumer perceptions of trans fats in 2009 show awareness of negative effects but
      limited concern regarding use in snack foods.
AB  - The purpose of this study was to determine consumers' perceptions of industrially
      produced trans fats. A cross-sectional study was conducted in Regina at 3
      different grocery store chains located in 3 different regions. A 21-item survey
      was administered in English by 3 research assistants at the grocery stores over a
      5-day period. Of 498 potential respondents who were approached, 211 completed the
      survey, for a 42% response rate. The majority of respondents were female and over
      61 years of age. When respondents were asked if they looked for information on
      food packages while grocery shopping, none of the respondents indicated that they
      looked for trans fat on the food label. Ninety-six percent of respondents
      identified that trans fat is found in processed foods, whereas 42% of respondents
      incorrectly identified trans fat as being found in nonhydrogenated margarines.
      More female respondents self-reported that they had made dietary changes to
      decrease trans fat intake as compared with male respondents (p < 0.05). Those
      participants who made dietary changes to decrease trans fat intake had higher
      mean knowledge scores than did those who did not make changes (p < 0.043). Sixty
      three percent of respondents indicated that they would not make dietary changes
      to their snack food selections even if their selections contained trans fat.
      Consumers know a little about trans fats and consider them to be a concern.
      However, consumers are reluctant to make dietary changes to limit these fats in
      their snack food selections.

PMID- 21854162
TI  - Bed-rest exercise, activity restriction, and high-risk pregnancies: a feasibility
      study.
AB  - This feasibility study investigated the response of maternal heart rate, blood
      pressure, and uterine contractions to a 30-min bed-rest exercise session (while
      listening to music) in hospitalized women with varying diagnoses of high-risk
      pregnancy. Eleven antenatal women who were hospitalized for activity restriction
      were assigned randomly to either a bed-rest exercise and music group (n = 6) or a
      bed-rest and music group (n = 5) that involved no exercise. The key findings were
      that there were no changes in maternal blood pressure or in the number of uterine
      contractions following the exercise intervention. A supervised bed-rest exercise
      intervention may, therefore, provide minimal risks and help alleviate the
      physiological effects of hospital activity restriction.

PMID- 21854163
TI  - Pattern of growth of very low birth weight preterm infants, assessed using the
      WHO Growth Standards, is associated with neurodevelopment.
AB  - Several Canadian professional organizations recently recommended that the growth
      of preterm infants be monitored using the World Health Organization Growth
      Standards (WHO-GS) after hospital discharge. The WHO-GS are a prescriptive set of
      growth charts that describe how term infants should grow under ideal
      environmental conditions. Whether preterm infants following this pattern of
      growth have better outcomes than infants that do not has yet to be evaluated. Our
      aim was to determine whether the pattern of growth of very low birth weight
      (VLBW) infants during the first 2 years, assessed using the WHO-GS or the
      traditional Centers for Disease Control and Prevention reference growth charts
      (CDC-RGC), is associated with neurodevelopment. Pattern of weight, length, and
      head circumference gain of appropriate-for-gestation VLBW preterm infants (n =
      289) from birth to 18-24 months corrected age was classified, using the WHO-GS
      and CDC-RGC, as sustained (change in Z-score <=1 SD), decelerated (decline >1
      SD), or accelerated (incline >1 SD). Development was assessed using the Bayley
      Scales of Infant and Toddler Development (BSID)-III at 18-24 months corrected
      age. Using the WHO-GS, children with a decelerated pattern of weight gain had
      lower cognitive (10 points), language (6 points), and motor (4 points) scores
      than infants with sustained weight gain (p < 0.05), even after adjustment for
      morbidities. No association was found using the CDC-RGC. In conclusion, a
      decelerated pattern of weight gain, determined with the WHO-GS, but not the CDC
      GRC, is associated with poorer neurodevelopment scores on the BSID-III than a
      pattern of sustained growth.

PMID- 21854164
TI  - Inhibitory effects of Schizandra chinensis extract on atopic dermatitis in NC/Nga
      mice.
AB  - CONTEXT: Schizandra chinensis Baillon (SC) is traditionally used as a medicinal
      plant in the Orient. Recently, SC has become recognized as an adaptogen by the
      mainstream medical community. Phytoadaptogens influence respiratory,
      cardiovascular, uterus myotonic, and immune activities. Atopic dermatitis (AD) is
      an allergic inflammatory skin disease caused by aberrant and over-reactive immune
      responses. OBJECTIVE: This study assessed the suppressive effect of SC extract
      (SCE) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD in a NC/Nga mouse model.
      MATERIALS AND METHODS: AD was induced by topically applying 0.2% DNCB to the
      hairless-back of NC/Nga mice for 4 weeks. Treated mice received SCE or
      dexamethasone after AD induction. RESULTS: SCE markedly suppressed DNCB-induced
      dermatitis, as determined by a count of scratching frequency; measurement of IgE,
      IgM, and histamine levels in serum; and histological observation of epidermal
      hyperplasia and mast-cell infiltration. Additionally, SCE lessened DNCB-induced
      histamine receptor mRNA expression in skin tissue and the splenic expressions of
      interleukin (IL)-4, IL-5, and high-affinity IgE receptor B protein. CONCLUSION:
      SCE appears useful for suppression of AD, even though the active pathway(s)
      remain unknown.

PMID- 21854165
TI  - Immune responses to lipopolysaccharide challenge in a tropical rodent (Funambulus
      pennanti): photoperiod entrainment and sex differences.
AB  - Annual variation in day length (photoperiod) triggers changes in the immune
      system of seasonal breeders. The rationale behind this study was to delineate any
      sex differences in immune responses of photoperiodically entrained animals
      challenged against lipopolysaccharide (LPS)-induced inflammatory stress. We
      observed that photoperiodically entrained [short day, SD, 10 h light (L):14 h
      dark (D); long day, LD, 16 h L:8 h D; and natural day length, NDL, 12 h L:12 h D]
      male and female Indian palm squirrels, Funambulus pennanti, presented sexual
      dimorphism in immune status after LPS-induced stress. Females presented high
      humoral (anti-keyhole limpet hemocyanin immunoglobulin) and cellular immunity
      (lymphocyte proliferation) compared with the males of all photoperiodic
      conditions. Female squirrels showed reduced pro-inflammatory cytokine levels
      (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) than the
      males suggesting their high efficiency to recover from LPS-induced inflammatory
      stress. Increased duration of melatonin secretion and corticosterone
      concentration in squirrels experiencing SD evidently supported survival of
      squirrels as compared with control (NDL) and LD squirrels of both sexes.
      Decreased immune status in both sexes under LD condition might be due to a short
      melatonin signal mimicking the LDs of summer. Thus, we infer that photoperiodic
      entrainment via the levels of melatonin and corticosterone synergistically
      supported more the survival of female squirrels under LPS-induced stress.

PMID- 21854166
TI  - Epigenetic programming of the HPA axis: early life decides.
AB  - Stress during early life can impact the developing brain and increase
      vulnerability to mood disorders later in life. Here, we argue that epigenetic
      mechanisms can mediate the gene-environment dialogue in early life and give rise
      to persistent epigenetic programming of adult physiology eventually resulting in
      disease. Early life stress in mice leads to epigenetic marking of the arginine
      vasopressin (AVP) gene underpinning sustained expression and increased
      hypothalamic-pituitary-adrenal axis activity. This epigenetic memory is laid down
      in the parvocellular neurons of the paraventricular nucleus and involves
      Ca(2+)/calmodulin kinase-mediated phosphorylation of the methyl-CpG binding
      domain protein MeCP2 leading to dissociation from its DNA-binding site and
      derepression of the AVP gene. The reduced occupancy of MeCP2 during this early
      stage of life facilitates the development of hypomethylation at the AVP enhancer,
      which sustains derepression throughout later life and thereby serves to hardwire
      early life experiences. The sequential order of these events may represent a
      critical time window for the preventive therapy of severe trauma.

PMID- 21854167
TI  - Sex differences in prenatally programmed anxiety behaviour in rats: differential
      corticotropin-releasing hormone receptor mRNA expression in the amygdaloid
      complex.
AB  - We recently reported that male, but not female, offspring born to mothers exposed
      to social stress during late gestation show heightened anxiety-type behaviour in
      adulthood. The amygdala organises anxious behaviour, which involves actions of
      corticotropin-releasing hormone (CRH). CRH gene expression and/or its release are
      increased in the amygdala in prenatally stressed (PNS) rats. CRH type 1 receptor
      (CRH-R1) mediates actions of CRH and urocortin I to promote anxiety-like
      behaviour, whereas the CRH type 2 receptor (CRH-R2) may mediate anxiolytic
      actions, through actions of urocortins 2 and 3. Here, using quantitative in situ
      hybridisation, we investigated whether altered CRH receptor mRNA expression in
      the amygdaloid nuclei may explain the sex differences in anxiety behaviour in
      adult male and female PNS rats. CRH-R1 mRNA expression was significantly greater
      in the central amygdala and basolateral amygdala (BLA) in male PNS rats compared
      with controls, with no change in the basomedial amygdala (BMA) or medial amygdala
      (MeA). In PNS females, CRH-R1 mRNA expression was greater than controls only in
      the MeA. Conversely, CRH-R2 mRNA expression was significantly lower in the BMA of
      male PNS rats compared with controls, but greater in female PNS rats, with no
      change in the BLA or MeA in either sex. The ratio of CRH-R1:CRH-R2 mRNA in the
      amygdaloid nuclei was generally increased in PNS males, but not in the PNS
      females. In conclusion, sex differences in anxiety-type behaviour in PNS rats may
      be explained by differential mRNA expression for CRH-R1 (pro-anxiogenic) and CRH
      R2 (pro-anxiolytic) in the amygdaloid complex.

PMID- 21854168
TI  - Peripheral oxytocin administration buffers autonomic but not behavioral responses
      to environmental stressors in isolated prairie voles.
AB  - Negative social experiences such as social stressors and isolation influence
      mental and physical illnesses, including affective disorders and heart disease.
      Studies focused on socially monogamous prairie voles can provide insight into
      neurobiological systems that underlie the consequences of negative social
      interactions. Female prairie voles were exposed to 28 days of social isolation or
      pairing with a female sibling (control). Voles were administered daily oxytocin
      [20 MUg/50 MUl, subcutaneous (sc)] or saline vehicle (50 MUl, sc) for 14 days and
      exposed to two behavioral stressors [elevated plus maze (EPM) and resident
      intruder test]. Brain tissue was collected for analysis of central peptide levels
      in the hypothalamic paraventricular nucleus (PVN). Isolation produced autonomic
      changes [increased heart rate (HR) and decreased HR variability) during both
      acute stressors and increased anxiety behaviors in the EPM. Oxytocin injection
      prevented the autonomic consequences of the acute stressors in isolated prairie
      voles, but did not affect the behaviors tested under the present conditions.
      Oxytocin had no effect on the behavioral or autonomic responsiveness in paired
      prairie voles. Oxytocin injection may exert a beneficial effect on autonomic
      responses to stressors in isolated animals through increasing the number of
      oxytocin-containing neurons and decreasing the number of corticotropin-releasing
      hormone-containing neurons in the PVN. Oxytocinergic mechanisms may serve to
      compensate for autonomic responses associated with chronic isolation and exposure
      to both social and non-social acute stressors.

PMID- 21854169
TI  - Isolated compounds from Sorghum bicolor L. inhibit the classical pathway of the
      complement.
AB  - The present study evaluated the anticomplement effects from isolated compounds of
      Sorghum bicolor in classical pathway complement system. Using column
      chromatograph, three compounds; Sorgoleone-362 (1), Sorgoleone-360 (2) and
      Sorgoleone-386 (3) were isolated and evaluated for in vitro anticomplement
      activity. Sorgoleone-386 showed inhibitory activity against complement system
      with 50% inhibitory concentrations (IC(50)) values of 148.3MUg/ml. This is the
      first report of anticomplement activity of isolated compounds from Sorghum
      bicolor.

PMID- 21854171
TI  - Chemical constituents from the roots of Xanthium sibiricum.
AB  - Xanthium sibiricum patrin ex Widder (Compositae) is an annual herb which grows
      all around China. Chemical investigations of its roots resulted in the
      identification of 15 compounds: stigmast-4-en-6beta-ol-3-one (1), beta
      sitostenone (2), beta-sitosterol (3), nonadecanoic acid (4), 5alpha,8alpha
      epidioxy-22E-ergosta-6,22-dien-3beta-ol (5), scopoletin (6), Jatrocin B (7), (+/
      )syringaresinol (8), 9,9'-O-di-(E)-feruloyl-(-)-secoisolariciresinol (9),
      cleomiscosin A (10), cleomiscosin C (11), N-trans-feruloyl tyramine (12),
      daucosterol (13), 5-methyluracil (14) and uracil (15). Structures were elucidated
      by spectroscopic (NMR and MS) methods and confirmed by comparing with reference
      samples and literature data. Compounds 1-2, 4-12, 14, and 15 were isolated from
      this genus for the first time, while this is the first report of
      coumarinolignoids in the Compositae family, and coumarinoligoids could be
      considered as valuable chemotaxonomic markers for the plant.

PMID- 21854170
TI  - Immunomodulatory effect of Parsley (Petroselinum crispum) essential oil on immune
      cells: mitogen-activated splenocytes and peritoneal macrophages.
AB  - INTRODUCTION: Parsley (Petroselinum crispum) has been traditionally used for the
      treatment of allergy, autoimmune and chronic inflammatory disorders. The present
      study aims to investigate the suppressive effects of parsley essential oil on
      mouse splenocytes and macrophages cells. METHODS AND MATERIALS: Parsley essential
      oil was harvested. It was treated on splenocytes and phytohemagglutinin (PHA) (5
      MUg/mL) and lipopolysaccharide (LPS) (10 MUg/mL) activated splenocytes in
      different concentrations (0.01-100 MUg/mL); then, proliferation was assayed by
      methyl tetrazolium (MTT) method. Treatment was also performed on the macrophages
      and LPS-stimulated macrophages (10 MUg/ml) and the nitrite levels were measured
      using the diazotization method based on the Griess reaction and MTT assay for
      evaluation of the viability of the macrophages. RESULTS: Proliferation of
      splenocytes in all the treated groups was suppressed. In PHA-stimulated
      splenocytes, the suppression was seen in all the examined concentrations (0.01
      100 MUg/mL), while in the unstimulated and LPS-stimulated groups suppression was
      relatively dose dependent and in high concentration (10 and100 MUg/mL).The
      viability of the macrophages in all groups was the same and in the unstimulated
      groups; NO suppression was significant in all the concentrations but in LPS
      stimulated groups, it was significant in the three higher concentrations (1, 10,
      and100 MUg/mL). CONCLUSION: The results of this study indicate that parsley
      essential oil may be able to suppress the cellular and humoral immune response.
      It can also suppress both NO production and the functions of macrophages as the
      main innate immune cells. These results may suggest that parsley essential oil is
      a proper suppressant for different applications.

PMID- 21854172
TI  - Composition and antimicrobial activity of the essential oil of Heracleum
      thomsonii (Clarke) from the cold desert of the western Himalayas.
AB  - Volatile oil composition of hydro-distilled (HD) and supercritical carbon dioxide
      (SC-CO(2)) essential oil of freshly collected aerial parts of Heracleum thomsonii
      (Umbeliferae) from the western Himalayas was studied by GC-FID and GC-MS. Results
      revealed qualitative and quantitative dissimilarity in the composition of hydro
      distilled and SC-CO(2) extracted oils. Nineteen constituents, which accounted for
      89.32% of total constituents in HD oil, represented by limonene (4.31%), (Z)-beta
      ocimene (3.69%), terpinolene (22.24%), neryl acetate (36.19%), nerol (9.51%) and
      p-cymene-8-ol (2.61%) were identified. In SC-CO(2) extracted oil, 24 constituents
      representing 89.95% of total constituents were identified. Terpinolene (5.08%),
      germacrene D (2.17%), neryl acetate (51.62%), nerol (9.78%), geranyl acetate
      (2.06%), alpha-bisabolol (2.48%) and 1-nonadecanol (4.96%) were the dominating
      constituents. In vitro antimicrobial activity of hydro-distilled oil was
      conducted against microrobial strains including two Gram-positive (Staphylococcus
      aureus and Bacillus subtilis) and five Gram-negative (Burkholderia cepacia,
      Escherichia coli, Enterobacter cloacae, Klebseilla pneumoniae and Pseudomonas
      aeruginosa) bacteria as well as seven fungi (Candida albicans, Issatchenkia
      orientalis, Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus,
      Aspergillus sydowii and Trichophyton rubrum) using broth microdilution method.
      The results of bioassay showed that the oil exhibited moderate to high
      antimicrobial activity against fungi C. albicans (MIC 625 ug ml(-1)), A.
      parasiticus (MIC 312.5 ug ml(-1)), A. sydowii (MIC 312.5 ug ml(-1)), T. rubrum
      (MIC 625 ug ml(-1)), Gram-positive bacteria B. subtilis (MIC 625 ug ml(-1)) and
      Gram-negative bacteria P. aeruginosa (MIC 312.5 ug ml(-1)).

PMID- 21854173
TI  - Chemical fingerprinting of Equisetum arvense L. using HPTLC densitometry and
      HPLC.
AB  - Equisetum arvense L. is a herbaceous medicinal plant, commonly known as
      horsetail, whose extracts have been reported to possess diuretic and haemostatic
      properties. The aim of this study was to evaluate the use of fingerprint
      chromatographic methods on commercially available raw materials or preparations
      of E. arvense L. in order to ascertain their quality and identify possible
      adulterants using HPLC and HPTLC densitometry. Two chromatographic methods were
      used to determine the chemical fingerprints of E. arvense and other allied
      species. The first was based on HPTLC identification followed by densitometric
      measurement at 350 nm. The second was based on HPLC separation. The ease of
      sample preparation and the possibility of simultaneous analysis of several
      samples in a short time make HPTLC a method of choice for the comprehensive
      quality evaluation of herbal products.

PMID- 21854174
TI  - Comparative studies of volatile oil composition of Rhododendron anthopogon by
      hydrodistillation, supercritical carbon dioxide extraction and head space
      analysis.
AB  - Volatile oil composition of the leaves of Rhododendron anthopogon (Ericaceae)
      growing wild in alpine Western Himalaya was studied using different extraction
      techniques including SC-CO(2) extraction and hydrodistillation (HD). Results from
      different extraction methodologies were compared with headspace analysis (HS) and
      evaluated for the effectiveness of techniques in characterisation of various
      terpene categories and to assess their influence on the yield and composition of
      volatiles. Variability in constituents and in quantitative yields was observed.
      The results varied with different extraction methods. A total of 27 constituents
      in SC-CO(2) extraction, 31 in HD and 17 in HS analysis were identified.
      Constituents in SC-CO(2) and HD oils were identified by gas chromatography mass
      spectrometry analysis. SC-CO(2) extraction was carried out at 40 degrees C and
      140 bar pressure and the oil represented by major constituents as beta
      caryophyllene (5.96%), alpha-humulene (4.06%) and p-menthadiene-2,9-diol (7.28%);
      in HD, oil limonene (11.26%), beta-caryophyllene (11.62%), alpha-humulene
      (7.22%), and E-nerolidol (5.83%) dominated the oil and in HS analysis, limonene
      (24.14%), gamma-terpinene (40.73%), alpha-terpinene (4.92%), beta-phellandrene
      (3.44%) and beta-ocimene (7.15%) were present as major constituents.

PMID- 21854175
TI  - Simultaneous determination of bioactive compounds in Piper nigrum L. and a
      species comparison study using HPLC-PDA.
AB  - Piper nigrum L. is a traditional medicine widely used in India for illnesses such
      as constipation, diarrhoea, earache, gangrene, heart disease, hernia, hoarseness,
      indigestion, insect bites, insomnia, joint pain, liver problems, lung disease,
      oral abscesses, sunburn, tooth decay and toothaches. In this study, six bioactive
      compounds, namely piperine (1), pellitorine (2), guineensine (3), pipnoohine (4),
      trichostachine (5) and piperonal (6) were quantified in different extracts of P.
      nigrum L. and compared with those of P. longum L. and P. chaba Hunter. To
      evaluate the quality of P. nigrum, a simple, accurate and precise HPLC-PDA method
      was developed for the simultaneous determination of the above-mentioned six
      compounds. The separation was achieved by Phenomenex Luna RP C(18) column (150 *
      4.6 mm, 5 um, Phenomenex Inc, CA, USA) with a binary gradient solvent system of
      water-acetonitrile, at a flow rate of 1.0 mL min(-1) and detected at 210, 232,
      262 and 343 nm. All six calibration curves showed good linearity (R (2) >
      0.9966). The method was reproducible with intra- and inter-day variations of less
      than 2% and 5%, respectively. The results demonstrated that this method is
      simple, reliable and suitable for the quality control of these plants.

PMID- 21854176
TI  - The effects of fatigue on performance in simulated nursing work.
AB  - Fatigue is associated with increased rates of medical errors and healthcare
      worker injuries, yet existing research in this sector has not considered multiple
      dimensions of fatigue simultaneously. This study evaluated hypothesised causal
      relationships between mental and physical fatigue and performance. High and low
      levels of mental and physical fatigue were induced in 16 participants during
      simulated nursing work tasks in a laboratory setting. Task-induced changes in
      fatigue dimensions were quantified using both subjective and objective measures,
      as were changes in performance on physical and mental tasks. Completing the
      simulated work tasks increased total fatigue, mental fatigue and physical fatigue
      in all experimental conditions. Higher physical fatigue adversely affected
      measures of physical and mental performance, whereas higher mental fatigue had a
      positive effect on one measure of mental performance. Overall, these results
      suggest causal effects between manipulated levels of mental and physical fatigue
      and task-induced changes in mental and physical performance. STATEMENT OF
      RELEVANCE: Nurse fatigue and performance has implications for patient and
      provider safety. Results from this study demonstrate the importance of a
      multidimensional view of fatigue in understanding the causal relationships
      between fatigue and performance. The findings can guide future work aimed at
      predicting fatigue-related performance decrements and designing interventions.

PMID- 21854177
TI  - Pathogenicity of avian leukosis viruses related to fowl glioma-inducing virus.
AB  - Fowl glioma-inducing virus (FGV), which belongs to avian leukosis virus subgroup
      A, causes the so-called fowl glioma and cerebellar hypoplasia in chickens. In the
      present study, the complete nucleotide sequences of four isolates (Tym-43, U-1,
      Sp-40 and Sp-53) related to the FGV prototype were determined and their
      pathogenicity was investigated. Phylogenetic analysis showed that the 3'-long
      terminal repeat of all isolates grouped together in a cluster, while sequences of
      the surface (SU) proteins encoded by the env gene of these viruses had 85 to 96%
      identity with the corresponding region of FGV. The SU regions of Tym-43, U-1 and
      FGV grouped together in a cluster, but those of Sp-40 and Sp-53 formed a
      completely separate cluster. Next, C/O specific-pathogen-free chickens were
      inoculated in ovo with these isolates as well as the chimeric virus RCAS(A)
      (FGVenvSU), constructed by substituting the SU region of FGV into the retroviral
      vector RCAS(A). The four variants induced fowl glioma and cerebellar hypoplasia
      and the birds inoculated with Sp-53 had the most severe lesions. In contrast,
      RCAS(A)-(FGVenvSU) provoked only mild non-suppurative inflammation. These results
      suggest that the ability to induce brain lesions similar to those of the FGV
      prototype is still preserved in these FGV variants.

PMID- 21854178
TI  - Seven-days-ahead forecasting of childhood asthma admissions using artificial
      neural networks in Athens, Greece.
AB  - Artificial Neural Network (ANN) models were developed and applied in order to
      predict the total weekly number of Childhood Asthma Admission (CAA) at the
      greater Athens area (GAA) in Greece. Hourly meteorological data from the National
      Observatory of Athens and ambient air pollution data from seven different areas
      within the GAA for the period 2001-2004 were used. Asthma admissions for the same
      period were obtained from hospital registries of the three main Children's
      Hospitals of Athens. Three different ANN models were developed and trained in
      order to forecast the CAA for the subgroups of 0-4, 5-14-year olds, and for the
      whole study population. The results of this work have shown that ANNs could give
      an adequate forecast of the total weekly number of CAA in relation to the
      bioclimatic and air pollution conditions. The forecasted numbers are in very good
      agreement with the observed real total weekly numbers of CAA.

PMID- 21854179
TI  - Molecular characterization of infectious bronchitis virus isolates from Russia
      and neighbouring countries: identification of intertypic recombination in the S1
      gene.
AB  - Infectious bronchitis virus (IBV) isolates recovered in Russia, Ukraine, and
      Kazakhstan between 2007 and 2010 were subjected to molecular characterization and
      compared with those isolated a decade ago. The IBV genome was detected in 202 out
      of 605 field samples from chickens with various clinical signs. Partial
      sequencing of the S1 gene revealed 153 vaccine strains and 49 field isolates of
      several genetic groups. Massachusetts, 793/B and D274 remained the predominant
      IBV genotypes along with QX, whereas B1648, Italy-02, Arkansas and variants
      accounted for about 12% of the total number. Three IBVs contained recombinant S1
      gene sequences comprising genome fragments of QX-type field isolates and vaccine
      strains H120 (UKR/02/2009) or 4/91 (RF/03/2010), and vaccine strains H120 and
      D274 (RF/01/2010). The results of the present study showed a significant decline
      in prevalence of variant IBVs and a further spread of QX-type isolates in
      commercial chicken flocks in Russia as compared with the 1998 to 2002 data.

PMID- 21854180
TI  - A turkey rhinotracheitis outbreak caused by the environmental spread of a vaccine
      derived avian metapneumovirus.
AB  - Avian metapneumovirus (aMPV) subtype A was isolated from 7-week-old turkeys
      showing respiratory disease typical of turkey rhinotracheitis. Comparison of the
      virus sequence with previously determined vaccine marker sequences showed that
      the virulent virus had originated from a licensed live subtype A aMPV vaccine.
      The vaccine had neither been in use on the farm within a period of at least 6
      months nor had it been used on farms within a distance of approximately 5 km.
      Isolation of the virus and exposure to naive turkeys caused disease typical of a
      virulent aMPV field strain. The study shows that disease was caused by exposure
      to aMPV vaccine-derived virus that was present in the environment, and indicates
      that such virus is able to circulate for longer than was previously envisaged.

PMID- 21854181
TI  - Naturally occurring phytotoxins in allelopathic plants help reduce herbicide dose
      in wheat.
AB  - Field studies were carried out to evaluate the influence of allelopathic plant
      water extracts applied alone or tank-mixed with a reduced herbicide dose on the
      weeds of wheat. Water extracts of sorghum (Sorghum bicolor (L.) Moench.) +
      sunflower (Helianthus annuus L.) + mulberry (Morus alba L.) were used alone (each
      at 20 L ha(-1)) or combined with iodo + mesosulfuron (3.6 and 7.2 g active
      ingredient (a.i.) ha(-1); 25 and 50% of the recommended dose, respectively). The
      recommended dose of herbicide, a weedy check and a weed-free treatment were
      included for comparison. Allelopathic water extracts alone suppressed the density
      of canary grass (Phalaris minor Retz.) and wild oat (Avena fatua L.) by 34-42%,
      and dry weight by 59-67%. The mixture of allelopathic plant water extracts
      combined with reduced doses of iodo + mesosulfuron gave weed control equal to the
      recommended dose of the herbicide. Integration of plant water extracts with
      reduced herbicide rates provide effective weed control and a wheat yield
      comparable to using the recommended herbicide dose.

PMID- 21854182
TI  - Branched-chain amino acids complex inhibits melanogenesis in B16F0 melanoma
      cells.
AB  - Present study was investigated the effect of each or complex of three branched
      chain amino acids (BCAAs; isoleucine, leucine, and valine) on melanin production
      in B16F0 melanoma cells treated with various concentrations (1-16 mM) for 72 h.
      Among the 20 amino acids, lysine and glycine showed the highest activities of
      DPPH radical scavenging and mushroom tyrosinase inhibition, respectively. Each
      and combination of BCAAs reduced melanogenesis in a concentration-dependent
      manner without any morphological changes and cell viability in melanoma cells.
      Present study was also investigated the inhibitory effects of each or complex of
      BCAAs at each 10 mM concentration on the 100 MUM IBMX-mediated stimulation of
      melanogenesis in melanoma cells for 72 h and found that IBMX treatment was
      stimulated to enhance melanin synthesis and that the complex of BCAAs was the
      most effectively inhibited in the melanin amounts of cellular and extracellular
      and the whitening the cell pellet. When the inhibitory effect of BCAAs on
      tyrosinase was examined by intracellular tyrosinase assay, both isoleucine and
      valine exhibit slightly inhibition, but leucine and combination of BCAAs did not
      inhibit the cell-derived tyrosinase activity. Present study demonstrated that
      complex of BCAAs inhibited melanin production without changes intercellular
      tyrosinase activity. Thus, the complex of BCAAs may be used in development of
      safe potentially depigmenting agents.

PMID- 21854183
TI  - Effect of fermented Angelicae gigantis Radix on carbon tetrachloride-induced
      hepatotoxicity and oxidative stress in rats.
AB  - This study is aimed to evaluate the protective effect of fermented Angelicae
      gigantis Radix (AGR) with Monascus purpureus strain on carbon tetrachloride
      (CCl(4))-induced hepatotoxicity and oxidative stress in rats. The activities of
      liver marker enzymes, alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), lactate dehydrogenase (LDH), and the levels of lipid peroxidation were
      increased when CCl(4) was treated but these parameters were significantly
      decreased by fermented AGR treatment. CCl(4) treatment exhibited decrease in
      serum concentrations of triglyceride, total cholesterol, HDL-cholesterol, and
      free fatty acids, and these were also decreased by fermented AGR administration.
      The level of serum leptin was significantly lower in fermented AGR administration
      than that in normal control group. CCl(4) treatment significantly increased the
      concentration of liver triglyceride. The current study observed significant
      elevations of the thiobarbituric acid-reactive substances (TBARS) levels in the
      liver homogenate, mitochondrial, and microsomal fractions of CCl(4) control group
      compared with normal control group. CCl(4) treatment resulted in a significant
      decrease in the levels of plasma and hepatic glutathione, but these reductions
      were significantly increased by fermented AGR administration. CCl(4) induced the
      marked hepatocytes necrosis and fatty accumulation around the central veins.
      Accordingly, fermented AGR may be an ideal candidate for the hepatoprotective
      effect in animal model.

PMID- 21854184
TI  - Combination of midazolam and a cyclooxygenase-2 inhibitor inhibits
      lipopolysaccharide-induced interleukin-6 production in human peripheral blood
      mononuclear cells.
AB  - CONTEXT: Interleukin-6 (IL-6) plays an important role in immune and inflammatory
      responses. Midazolam has been reported to modulate IL-6 response. Cyclooxygenase
      (COX) inhibitors, which are used together with midazolam in some patients
      undergoing surgery, also modulate it. We hypothesized that their combination
      results in eliciting the synergistical effect on the IL-6 response. OBJECTIVE:
      The aim of the present study was to evaluate the effect of the combination of
      midazolam and a COX inhibitor on IL-6 production. MATERIALS AND METHODS:
      Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers
      and incubated with lipopolysaccharide (LPS), midazolam, and/or COX inhibitors,
      including indomethacin, SC-560, a COX-1 selective inhibitor, and NS-398, a COX-2
      selective inhibitor. The supernatant concentrations of IL-6 and prostaglandins
      (PGs), including PGE2, PGF2alpha, PGD2, and 15-deoxy-Delta12,14-prostaglandin J2
      (15dPGJ2) were measured. RESULTS: Midazolam had no effect on IL-6 production in
      the cells incubated for 12 h, and any COX inhibitors also had no effect. However,
      the combination of midazolam and NS-398 significantly inhibited it. Midazolam
      raised the concentration of 15dPGJ2 in the supernatant of the cells, but not the
      concentration of other PGs. DISSCUSSION AND CONCLUSION: The results in the
      present study demonstrated that the combination of midazolam and a COX-2
      inhibitor inhibited LPS-induced IL-6 production in human PBMCs even if each drug
      separately did not have any effect on it. The finding suggests that their
      combination is effective against excessive IL-6 production such as severe
      inflammatory response and that the effect of midazolam on IL-6 production is
      possibly elicited via 15dPGJ2.

PMID- 21854185
TI  - rhPLD2 suppresses chronic inflammation reactions in a guinea pig asthma model.
AB  - BACKGROUND: Asthma is a complex inflammatory disorder of the airways, and
      research on alternative therapeutic strategies has attracted attention. This
      study aimed at hypersusceptibility and toxicity of recombinant human
      phospholipase D2 (rhPLD2) in guinea pigs. We determined the behavioral responses
      in the model of immediate hypersensitivity animals and changes of eosinophil
      levels following use of the drugs. Special attention was given to the effects of
      rhPLD2 in vivo on the guinea pig with chronic persistent asthma and the mechanism
      involved. METHODS: To investigate the effect of rhPLD2 on the expression of
      protein kinase C (PKC), and to examine the activity of signal transducer and
      activator of transcription 1 and 5a in the lung of the guinea pig with chronic
      asthma. Guinea pigs with chronic asthma were divided into five groups: a saline
      group, a dexamethasone 5.0 mg group, and rhPLD2 (1.5, 2, or 3 mg) groups. Non
      sensitized animals were as normal control group. PKC expression was measured by
      immunohistochemistry, alterations of STAT1 and STAT5a were detected by TransAM
      transcription factor assay kits. RESULTS: rhPLD2 (3.0 mg) decreased PKC
      expression to baseline and inhibited STAT1 activity compared with that of the
      saline group (p < 0.01). CONCLUSION: The rhPLD2 may suppress the chronic
      inflammatory reaction through down-regulating PKC expression and STAT1/STAT5a
      activity in the lung. The rhPLD2 may be a suitable therapeutic target for asthma.

PMID- 21854188
TI  - In vitro expansion of human gammadelta and CD56(+) T-cells by Aspergillus-antigen
      loaded fast dendritic cells in the presence of exogenous interleukin-12.
AB  - Aspergillus fumigatus (Af) infection is especially prevalent after allogenic bone
      marrow transplantation (BMT) and causes invasive pulmonary aspergillosis. Human
      gammadelta T-cells have essential role in maintaining immune homeostasis and in
      the resistance of pathogens and tumors. Also, gammadelta T-cells may facilitate
      stem cells engraftment and decrease a life-threatening graft versus host disease
      after allogenic BMT. Moreover, expression of CD56 molecules on gammadelta T-cells
      increases their antitumor cytotoxic activity. This study reveals that Af-pulsed
      fast dendritic cells (fast-DCs, which generated within only 72 h) plus IL-12 and
      then IL-2 can propagate autologous gammadelta and CD56(+) T-cells in vitro and
      this expansion is sustained by repeating the stimulation (107.5 +/- 13.9-fold and
      37.6 +/- 2.2-fold increase for gammadelta and CD56(+) T-cells, respectively,
      after three primings). Many of the expanded gammadelta and CD56(+) T-cells
      expressed CD8 molecules (29.6%-68.6%), while few of them expressed CD4 molecules
      (2.3%-17.5%). Also, ~28% of the expanded gammadelta T-cells were CD56(+). On the
      other hand, the proliferation of gammadelta and CD56(+) T-cells significantly
      decreased (p < 0.001, <19-fold and 12-fold, respectively) in the absence of
      either Af-pulsed fast-DCs or IL-12 or in the presence of un-pulsed fast-DCs,
      indicating the importance of Af-antigens and IL-12 in inducing this expansion.
      The expansion of gammadelta and CD56(+) T-cells did not hamper the generation of
      Af-specific alphabeta T-cell effectors. The methodology described in this study,
      utilizing autologous Af-pulsed fast-DCs and IL-12, permits the rapid generation
      of Af-specific alphabeta T-cell effectors and propagation of gammadelta and
      CD56(+) T-cells in vitro.

PMID- 21854189
TI  - Effect of tooth bleaching on shear bond strength of a fluoride-releasing sealant.
AB  - OBJECTIVE: To evaluate the effect of an in-office plus at-home bleaching protocol
      on shear bond strength of orthodontic buttons when using a fluoride-releasing
      sealant. MATERIALS AND METHODS: Extracted human molars (160) were randomly
      divided into bleached (n  =  80) and unbleached groups (n  =  80). The bleached
      group was treated with 45% carbamide peroxide for 30 minutes, followed by five
      applications of 20% carbamide peroxide at 24-hour intervals. After 2 weeks,
      lingual buttons were bonded on the teeth in both groups using either Transbond XT
      primer or Pro Seal sealant. The teeth were then stored in artificial saliva and
      subjected to shear testing at 24 hours and 3 months using a Zwick Universal Test
      Machine. Comparisons of mean shear bond strength values were made with the
      analysis of variance test. The Fisher's exact test was used to evaluate the
      adhesive remnant index scores. RESULTS: The analysis of variance of the 24-hour
      results indicated a significant difference between the four subgroups (P <
      .0011). Further simple t-tests indicated that the differences were significant
      only between bleached and unbleached subgroups (P < .0011). The 3-month results
      showed the mean shear bond strengths of the unbleached group using Pro Seal
      sealant was significantly lower than that of the other, though still greater than
      clinically minimal suggested bond strengths. Interestingly, 15% of the bleached
      teeth exhibited enamel fracture at the 3-month testing. CONCLUSION: Both Pro Seal
      sealant and Transbond XT primer demonstrated reliable shear bond strength values
      on both bleached and unbleached teeth over time.

PMID- 21854190
TI  - Costs of hospital events in patients with metastatic colorectal cancer.
AB  - BACKGROUND: In the last decade, the number of new agents, including monoclonal
      antibodies, being developed to treat metastatic colorectal cancer (mCRC)
      increased rapidly. While improving outcomes, these new treatments also have
      distinct and known safety profiles with toxicities that may require
      hospitalizations. However, patterns and costs of hospitalizations of toxicities
      of these new 'targeted' drugs are often unknown. OBJECTIVE: This study aimed to
      estimate the costs of hospital events associated with adverse events specified in
      the 'Special Warnings and Precautions for Use' section of the European Medicinal
      Agency Summary of Product Characteristics for bevacizumab, cetuximab, and
      panitumumab, in patients with mCRC. METHODS: From the PHARMO Record Linkage
      System (RLS), patients with a primary or secondary hospital discharge code for
      CRC and distant metastasis between 2000-2008 were selected and defined as
      patients with mCRC. The first discharge diagnosis defining metastases served as
      the index date. Patients were followed from index date until end of data
      collection, death, or end of study period, whichever occurred first. Hospital
      events during follow-up were identified through primary hospital discharge codes.
      Main outcomes for each event were length of stay and costs per hospital
      admission. RESULTS: Among 2964 mCRC patients, 271 hospital events occurred in 210
      patients (mean [SD] duration of follow-up: 34 [31] months). The longest mean (SD)
      length of stay per hospital admission were for stroke (16 [33] days), arterial
      thromboembolism (ATE) (14 [21] days), wound-healing complications (WHC), acute
      myocardial infarction (AMI), congestive heart failure (CHF), and neutropenia (all
      9 days; SD 5-15). Highest mean (SD) costs per admission were for stroke (?13,500
      [?28,800]), ATE (?13,300 [?18,800]), WHC (?10,800 [?20,500]). LIMITATIONS:
      Although no causal link could be identified between any specific event and any
      specific treatment, data from this study are valuable for pharmacoeconomic
      evaluations of newer treatments in mCRC patients. CONCLUSIONS: Inpatient costs
      for events in mCRC patients are considerable and vary greatly.

PMID- 21854191
TI  - Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on
      costs.
AB  - BACKGROUND: The clinical goal in the treatment of diabetes is to achieve good
      glycemic control. Tight glycemic control achieved with intensive glucose lowering
      treatment reduces the risk of long-term micro- and macro-vascular complications
      of diabetes, resulting in an improvement in quality-of-life for the patient and
      decreased healthcare costs. The positive impact of good glycemic control is,
      however, counterbalanced by the negative impact of an increased incidence of
      hypoglycemia. METHODS: A search of PubMed was conducted to identify published
      literature on the impact of hypoglycemia, both on patient quality-of-life and
      associated costs to the healthcare system and society. RESULTS: In people with
      type 1 or type 2 diabetes, hypoglycemia is associated with a reduction in quality
      of-life, increased fear and anxiety, reduced productivity, and increased
      healthcare costs. Fear of hypoglycemia may promote compensatory behaviors in
      order to avoid hypoglycemia, such as decreased insulin doses, resulting in poor
      glycemic control and an increased risk of serious health consequences. Every non
      severe event may be associated with a utility loss in the range of 0.0033-0.0052
      over 1 year, further contributing to the negative impact. LIMITATIONS: This
      review is intended to provide an overview of hypoglycemia in diabetes and its
      impact on patients and society, and consequently it is not a comprehensive
      evaluation of all studies reporting hypoglycemic episodes. CONCLUSION: To provide
      the best possible care for patients and a cost-effective treatment strategy for
      healthcare decision-makers, a treatment that provides good glycemic control with
      a limited risk of hypoglycemia would be a welcome addition to diabetes management
      options.

PMID- 21854192
TI  - Safety, pharmacokinetic, and pharmacodynamic profiles of ipragliflozin (ASP1941),
      a novel and selective inhibitor of sodium-dependent glucose co-transporter 2, in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The sodium-dependent glucose co-transporter 2 (SGLT2) is a high
      capacity, low-affinity transport system primarily expressed in the renal proximal
      tubules, where it plays an important role in the regulation of glucose levels.
      Inhibition of SGLT2 represents an innovative approach for plasma glucose control
      in type 2 diabetes mellitus (T2DM) by blocking glucose reabsorption and enhancing
      glucose loss in the urine. METHODS: This Phase 2, randomized, placebo-controlled
      study investigated the safety, tolerability, and pharmacokinetic and
      pharmacodynamic profiles of the novel oral SGLT2 inhibitor ipragliflozin
      (ASP1941) in T2DM patients. Sixty-one patients were randomized to placebo or
      ipragliflozin once daily at doses of 50, 100, 200, or 300 mg for 28 days.
      Patients were admitted to the clinic during the study and received a weight
      maintenance diet. RESULTS: The incidence of treatment-emergent adverse events was
      similar for placebo and ipragliflozin groups. There were no deaths, and no
      patients discontinued ipragliflozin because of adverse events. Ipragliflozin was
      absorbed rapidly, taking approximately 1 h to reach the maximum concentration.
      The area under the concentration-time curve and maximum ipragliflozin
      concentration at steady state displayed dose linearity. All ipragliflozin doses
      significantly reduced glycosylated hemoglobin, fasting plasma glucose, and mean
      amplitude of glucose excursions compared with placebo. Significant dose-dependent
      increases in urinary glucose excretion were observed in all ipragliflozin groups.
      Mean weight decreased in the placebo and ipragliflozin groups, with greater
      reductions occurring in ipragliflozin-treated patients. CONCLUSION: Ipragliflozin
      was generally safe, well tolerated, and effective at blocking renal glucose
      reabsorption and decreasing plasma glucose levels in T2DM patients.

PMID- 21854193
TI  - Comparison between sensor-augmented insulin therapy with continuous subcutaneous
      insulin infusion or multiple daily injections in everyday life: 3-day analysis of
      glucose patterns and sensor accuracy in children.
AB  - BACKGROUND: Sensor-augmented continuous subcutaneous insulin infusion (CSII)
      therapy is superior to CSII therapy alone, but little is known on the
      effectiveness of sensor-augmented multiple daily injections (MDI) therapy.
      METHODS: We compared during everyday life mean glucose control and several
      variability indexes recorded for 3 days by a real-time glucose sensor (Medtronic,
      Northridge, CA) in two groups of children treated with either CSII or MDI. Fifty
      five consecutive subjects were examined: 17 receiving CSII and 38 receiving MDI
      basal-bolus therapy (age range, 7-22 years). All subjects wore the sensor for 4
      days, and 3 days were used for statistical analysis. Mean glucose and SD,
      coefficient of variation (CV), mean amplitude of glucose excursion (MAGE), mean
      of daily differences (MODD), continuous overall net glycemic action (CONGA) at 2
      and 4 h, blood glucose (BG) rate, area under the curve (AUC) above 180 mg/dL and
      below 70 mg/dL, Low BG Index (LBGI), and High BG Index (HBGI) were calculated.
      RESULTS: Patients receiving CSII administered more daily boluses than patients
      receiving MDI (5.2+/-1.5 vs. 3.2+/-0.3, respectively; P=0.001). Mean glucose was
      lower in the CSII group. AUC above 180 mg/dL and HBGI were higher in the MDI
      group. CV, CONGA at 2 h, CONGA at 2 h during the day, and HBGI were worse in the
      MDI group, whereas MODD, LBGI, BG rate, and MAGE were similar. A positive
      correlation (r=0.95; P<0.05) was found between the paired sensor-meter values.
      For the glucose values <70 mg/dL, sensitivity was 40%, and specificity was 99%.
      CONCLUSIONS: In our pediatric patients during everyday life sensor-augmented CSII
      therapy seemed more effective than sensor-augmented MDI therapy, in terms both of
      glucose mean values and of intraday variability. Mild hypoglycemic episodes and
      indexes of low BG values were similar in the two groups, although the latter
      results may be inaccurate because of low sensor sensitivity at low glucose value.

PMID- 21854194
TI  - Distribution of polymorphisms in cytochrome P450 2B6, histocompatibility complex
      P5, chemokine coreceptor 5, and interleukin 28B genes in inhabitants from the
      central area of Argentina.
AB  - AIMS: The selection of the most appropriate treatment for several diseases relies
      on a number of factors such as environment, age, gender, and nutrition.
      Additionally, the contribution of different genetic polymorphisms to treatment
      efficacy has been largely recognized. The lack of information on the
      pharmacogenetic profile of our population prompted us to analyze the frequency of
      polymorphisms known to be relevant to achieve treatment efficacy with different
      therapeutic agents in viral infectious diseases, such as Hepatitis C and AIDS.
      RESULTS: The allelic frequencies for the wild-type variant of the genes analyzed
      were cytochrome P450 2B6 (CYP2B6; rs3745274; 516G) 0.618 (95% confidence interval
      [CI]: 0.523, 0.711), chemokine coreceptor 5 (CCR5; rs333) 0.961 (95% CI: 0.942,
      0.98), histocompatibility complex P5 (HCP5; rs2395029; 335T) 0.971 (95% CI:
      0.937, 1), and interleukin 28B (IL28B; rs12979860; 12007005C) 0.656 (95% CI:
      0.564, 0.747), respectively. CONCLUSIONS: Our data indicate that the genetic
      profile of the population studied is similar to that reported for other Caucasian
      populations, with only slight differences for CYP2B6. Noteworthy, the
      considerable number of patients carrying CYP2B6 (516T) and IL28B (12007005T)
      alleles underlies the importance of considering pharmacogenetic testing before
      starting drug therapy protocols to prevent toxicity and/or lack of effectiveness
      in AIDS or hepatitis C virus infections.

PMID- 21854196
TI  - Use of complementary and alternative medicine in a region of northwest Mexico.

PMID- 21854195
TI  - A G-to-T transversion at the splice acceptor site of dystrophin exon 14 shows
      multiple splicing outcomes that are not exemplified by transition mutations.
AB  - Mutations at splicing consensus sequences have been shown to induce splicing
      errors such as exon skipping or cryptic splice site activation. Here, we
      identified eight splicing products caused by a G-to-T transversion mutation at
      the splice acceptor site of exon 14 of the dystrophin gene (c.1603-1G>T).
      Unexpectedly, the most abundant product showed skipping of the two consecutive
      exons 14 and 15, and exon 14 skipping was observed as the second most abundant
      product. To examine the cause of this splicing multiplicity, minigenes containing
      dystrophin exons 14 and 15 with their flanking introns were constructed and
      subjected to in vitro splicing. Minigenes with the wild-type sequence or a G>A
      transition at position c.1603-1 produced only the mature mRNA. On the other hand,
      the minigenes with a G>T or G>C transversion mutation produced multiple splicing
      products. A time-course analysis of the in vitro splicing revealed that splicing
      of the middle intron, intron 14, was the first step in transcript maturation for
      all four minigene constructs. The identity of the mutant nucleotide, but not its
      position, is a factor leading to multiple splicing outcomes. Our results suggest
      that exon skipping therapy for Duchenne's muscular dystrophy should be carefully
      monitored for their splicing outcomes.

PMID- 21854197
TI  - Survey of the antimicrobial activity of commercially available Australian tea
      tree (Melaleuca alternifolia) essential oil products in vitro.
AB  - OBJECTIVES: The aim of this study was to investigate the antimicrobial activity
      of a range of commercially available tea tree oil (TTO) products and to evaluate
      whether formulation plays a significant part in their antiseptic activity.
      METHODS: The antimicrobial activity of the purchased products and control TTO
      solutions was assessed against Escherichia coli, Staphylococcus aureus,
      Salmonella typhimurium, Pseudomonas aeruginosa, and Candida albicans using well
      diffusion, broth microdilution, and broth macrodilution assays. RESULTS: Zone
      sizes obtained by the agar well diffusion assay ranged from 0 to 49.8 mm, with
      the more viscous and lipophilic products producing the smallest zones. Micro- and
      macrodilution methods showed that eight products had minimum inhibitory
      concentrations that were lower than the nonformulated TTO control. The remaining
      three products showed activity equivalent to the TTO control. CONCLUSIONS: In
      general, the commercially available antiseptic TTO products showed antimicrobial
      activity that was equivalent to, or greater than the nonformulated TTO control.
      This suggests that the TTO within these products has retained its antimicrobial
      activity. Furthermore, the enhanced activity of the products may be attributed to
      other antimicrobial excipients within the products such as preservatives, or to
      synergistic antimicrobial interactions between the TTO and other product
      excipients. The observation that the commercially available antiseptic TTO
      products tested in this study retained adequate antimicrobial activity emphasizes
      the importance of considering how product bases and excipients may interact with
      the active compound during formulation to ensure efficacy of the final product.
      Finally, the current data suggest that these TTO products may also be active in
      vivo. However, this can only be determined through further studies and in
      clinical trials.

PMID- 21854198
TI  - Different patterns of dynamic variations on electrical conductances of acupoints
      between Qi Vacuity and Qi non-Vacuity after glucose ingestion.
AB  - OBJECTIVES: In Traditional Chinese Medicine (TCM), Qi maintains the physiologic
      function and indicates physiologic energy. Glucose provides energy to humans,
      thereby playing a role analogous to "nutritive Qi." This study aims to identify
      the correlations among blood glucose, Qi Vacuity (QV), and the electrical
      conductances of acupoints. METHODS: Twenty (20) subjects who had ingested a
      glucose solution after a 10-hour overnight fast were divided into two groups
      based on QV score. Then their acupoint conductances were measured sequentially
      using a Ryodoraku instrument during the following 120 minutes. Data were analyzed
      using generalized estimating equations as a time-series model. RESULTS: Eight (8)
      subjects were categorized into a Qi Vacuous group for QV score >6, and the other
      12 subjects were categorized into a Qi non-Vacuous group for QV score <=6. During
      the first 30 minutes, the acupoint conductances decreased on the left
      Pericardium, left Heart, right Liver, Kidney, and Gallbladder meridians in the Qi
      Vacuous group, and increased on the right Pericardium meridian and decreased on
      the right Gallbladder meridian in the Qi non-Vacuous group. From 30 to 60 and 60
      to 90 minutes, the acupoint conductances decreased on the Gallbladder, Heart,
      left Pericardium, left Kidney, right Liver, and right Stomach meridians in the Qi
      Vacuous group, and increased on the Pericardium, Heart, left Small Intestine, and
      left Lung meridians in the Qi non-Vacuous group. During the last 30 minutes, more
      of the acupoint conductances were increased in the Qi non-Vacuous group, whereas
      only the acupoint conductance on the liver meridian was increased and that on the
      left gallbladder meridian was decreased in the Qi Vacuous group. CONCLUSIONS: The
      findings suggest that the energy distribution and transformation in meridian
      vessels present different patterns in QV and non-QV groups after glucose
      consumption.

PMID- 21854199
TI  - The effect of lavender oil on stress, bispectral index values, and needle
      insertion pain in volunteers.
AB  - OBJECTIVES: The purpose of this study was to investigate whether lavender oil
      aromatherapy can reduce the bispectral index (BIS) values and stress and decrease
      the pain of needle insertion in 30 volunteers. SUBJECTS AND METHODS: Thirty (30)
      healthy volunteers were randomly allocated to 2 groups: the experimental group
      received oxygen with a face mask coated with lavender oil for 5 minutes, and the
      control group received oxygen through a face mask with no lavender oil for 5
      minutes. The stress level (0=no stress, 10=maximum stress), BIS value, and pain
      intensity of needle insertion (0=no pain, 10=worst pain imaginable) were
      measured. RESULTS: There were no significant differences in age, sex, height, and
      weight between the two groups. Stress level, BIS value, and pain intensity of
      needle insertion before aromatherapy were similar between the two groups.
      However, the stress values (p<0.001) and BIS value (p<0.001) after aromatherapy
      were significantly reduced compared with the control. In addition, the pain
      intensity of needle insertion was significantly decreased after aromatherapy
      compared with the control (p<0.001). CONCLUSIONS: Lavender aromatherapy in
      volunteers provided a significant decrease in the stress levels and in the BIS
      values. In addition, it significantly reduced the pain intensity of needle
      insertion.

PMID- 21854200
TI  - The antiplatelet activity of camel urine.
AB  - BACKGROUND: For centuries, camel urine has been used for medicinal purposes and
      anecdotally proclaimed as a cure for a wide range of diseases. However, the
      apparent therapeutic actions of camel urine have yet to be subjected to rigorous
      scientific scrutiny. Recent preliminary studies from the authors' laboratory have
      indicated that camel urine possesses potent antiplatelet activity, not found in
      human or bovine urines, suggesting a possible role for camel urine in inhibiting
      platelet function. The goal of the current study was to characterize the
      antiplatelet activity of camel urine against normal human platelets based on
      agonist-induced aggregation and platelet function analyzer (PFA-100) closure
      time. MATERIALS AND METHODS: Urine was collected from healthy virgin, pregnant,
      and lactating camels aged 2-10 years. Platelet-rich plasma (PRP) was prepared
      from blood collected from healthy individuals' blood into citrated anticoagulant.
      Agonist-induced aggregometry using donor PRP and PFA-100 closure times in whole
      blood were carried out in the presence and absence of added camel urine. The
      responses of platelets to multiple doses of camel urine were also assessed. The
      experimental procedure was repeated in human and bovine urines. RESULTS: Camel
      urine completely inhibited arachidonic acid (AA) and adnosine diphosphate (ADP)
      induced aggregation of human platelets in a dose-dependent manner. PFA-100
      closure time using human whole blood was prolonged following the addition of
      camel urine in a dose-dependent manner. Virgin camel urine was less effective in
      inhibiting ADP-induced aggregation as compared to urine from lactating and
      pregnant camels; however, all three showed comparable inhibitory activity.
      Neither human nor bovine urine exhibited antiplatelet activity. CONCLUSIONS:
      Camel urine has potent antiplatelet activity against ADP-induced (clopidogrel
      like) and AA-induced (aspirin-like) platelet aggregation; neither human nor
      bovine urine exhibited such properties. These novel results provide the first
      scientific evidence of the mechanism of the presumed therapeutic properties of
      camel urine.

PMID- 21854201
TI  - Pure laparoscopic en bloc left hemihepatectomy and caudate lobe resection in
      patients with intrahepatic cholangiocarcinoma.
AB  - INTRODUCTION: There is an ongoing debate on whether it is safe to push the
      boundaries and widen the indications of laparoscopic liver surgery after careful
      patient selection. We report 2 cases of pure laparoscopic en bloc left
      hemihepatectomy and caudate lobe resection for intrahepatic cholangiocarcinoma
      (ICC). METHODS: The first patient (a 79-year old) had an ICC affecting segments
      2, 3, and 4 of the liver with dilatation of segment 1 ducts at preoperative
      imaging. The second patient (an 81-year old) had an ICC affecting segments 2, 3
      with local invasion of segment 1. Both patients underwent pure laparoscopic left
      hemihepatectomy and caudate lobe resection. RESULTS: The first patient's
      operative time was 360 minutes and blood loss was 390 mL. Postoperative hospital
      stay was 8 days. The definitive histology was as follows: pT1 ICC (25 mm in
      maximal diameter), with 20 mm free resection margin. The second patient's
      operative time was 310 minutes and blood loss was 300 mL. Postoperative hospital
      stay was 4 days. The definitive histology was as follows: T1 ICC (49 mm in
      maximal diameter) with 10 mm free resection margin. The first patient was disease
      free 12 months after surgery. The second patient died 11 months after surgery of
      metastatic disease. CONCLUSION: Pure laparoscopic left hemihepatectomy and
      caudate lobectomy for ICC may be feasible and safe. This is, however, a very
      complex procedure requiring extensive experience in laparoscopic liver surgery
      and careful patient selection to optimize surgical outcome. To our knowledge,
      this is the first systematic description of a pure laparoscopic en bloc left
      hemihepatectomy and caudate lobe resection for ICC.

PMID- 21854202
TI  - Treatment of retrocaval ureter by retroperitoneal laparoscopic
      ureteroureterostomy: experience on 12 patients.
AB  - OBJECTIVE: To present our experience and the feasibility of retroperitoneal
      laparoscopic ureteroureterostomy (LUUS) for treatment of retrocaval ureter (RCU).
      PATIENTS AND METHODS: A total of 12 patients with RCU underwent LUUS. To evaluate
      the retrocaval segment, we calibrated retrocaval segment by a number 8F catheter
      segment before laparoscopy. A three-port, finger-dissecting removal of the
      retroperitoneal fat, retroperitoneal approach was used. In all 12 cases, after
      the ureter had been released from the inferior vena cava (IVC), the ureter was
      transected at the lower part of the dilated ureter and positioned anterior to the
      IVC. A tension-free ureteroureteral anastomosis was completed with the
      intracorporal freehand suturing techniques. Follow-up studies were performed with
      intravenous urography and renal ultrasonography at 3 and 6 months
      postoperatively. RESULTS: All operations were laparoscopically completed with no
      open conversion. The mean operating time was 112 minutes (range 89-158), and the
      mean anastomosis time was 42 minutes, for all cases. The mean blood loss was 35
      mL (range 21-60). The retrocaval segments of the ureter were resected in 2 of 12
      cases, because the 8F catheter could not negotiate the segment. No intraoperative
      complications occurred. Hydronephrosis in all patients was decreased
      substantially after surgery, and all patients were symptom free. CONCLUSION: Our
      results have demonstrated that retroperitoneal LUUS was a safe and effective
      procedure, and an excellent minimally invasive treatment option for RCU.

PMID- 21854203
TI  - Outcome comparison among laparoscopic Duhamel, laparotomic Duhamel, and transanal
      endorectal pull-through: a single-center, 18-year experience.
AB  - PURPOSE: Transanal endorectal pull-through has changed the treatment of
      Hirschsprung's disease (HD) in the past decade. The aim of the study was to
      compare outcomes, obtained in a single center, with laparotomic Duhamel (LTD),
      laparoscopic Duhamel (LSD), and laparoscopic-assisted transanal endorectal pull
      through (LTEPT). MATERIALS AND METHODS: We retrospectively reviewed the charts of
      all patients operated on for HD since 1992. Preoperative, operative, and
      postoperative data were collected to compare short- and long-term outcomes among
      the three groups. RESULTS: From 1992 to 2010, 70 children were treated for HD.
      Patients were divided into three groups based on the surgical technique used: 14
      LTEPT, 32 LSD, and 24 LTD. Mean ages at surgery were 4.67, 14.61, and 13.28
      months, respectively. Patients in the LTEPT group had significant shorter
      operating times (195 versus 257 versus 291 minutes, P=.03), earlier start of
      feeding (1.2 versus 3.1 versus 4.7 days, P<.01), and shorter length of hospital
      stay (4.4 versus 6.8 versus 9.7 days, P<.011). Overall complications rate was
      lower in the LTEPT (14%) than in the LSD (31.2%) and LTD (29.7%) groups.
      Postoperative enterocolitis incidence was 3%-4% in the Duhamel groups and none in
      LTEPT. Long-term outcome showed less constipation and better continence for age
      in the LTEPT group at the 1-year follow-up (P=.033). CONCLUSIONS: This study
      further supports technical advantages, lighter impact of the surgical procedure
      on infants, lower incidence of complications, and better long-term outcome of the
      transanal pull-through compared to the Duhamel approaches.

PMID- 21854204
TI  - Laparoscopic splenectomy: comparison between anterior and lateral approaches.
AB  - AIM: Splenectomy, except for a traumatic purpose, is now performed through a
      laparoscopic approach. There are mainly two ways for laparoscopic total or
      partial splenectomies. For the classic anterior dissection of the splenic
      vessels, patient is placed in supine position and five ports are required to
      elevate the spleen and proceed to vessel divisions. With a lateral approach of
      the pedicle, patient is placed in lateral decubitus position and three ports are
      sufficient, because gravity help to provide traction on the splenic ligaments and
      to present hilar vessels and pancreas tail. The aim of our study was to compare
      surgical complications of those two approaches of laparoscopic splenectomy in
      children. METHODS: We reviewed 84 medical records of patient operated on for
      hematological disease between January 1993 and December 2009. RESULTS: There were
      47 anterior and 37 lateral approaches. Sex, disease, median age, operative time,
      blood lost or hospital stay, and associated laparotomy were not different between
      the two groups. Operative complications included hemorrhage (5), bowel injury
      (1), diaphragmatic wound (1), pancreas tail section (1), and parietal hematoma
      (1) in the anterior group (9 cases) versus 1 hemorrhage in the lateral group
      (P<.02). There were five laparotomies owing to surgical complications in the
      anterior group, and none in the lateral group. CONCLUSION: Splenectomy through
      laparoscopic approach is an effective technique. Lateral dissection of the
      vessels provides less operative complications in children.

PMID- 21854205
TI  - Learning curves in laparoscopic right-sided colon cancer surgery: a comparison of
      first-generation colorectal surgeon to advance laparoscopically trained surgeon.
AB  - BACKGROUND: We aimed to evaluate the learning curve (LC) for laparoscopic right
      sided colon cancer surgery (LRCCS) by comparing the results between two surgeons
      (first-generation colorectal surgeon versus laparoscopically trained surgeon).
      METHODS: The study was a retrospective analysis that evaluated 117 consecutive
      LRCCSs performed by two surgeons, the first-generation surgeon (Surgeon A) and
      laparoscopically trained surgeon (Surgeon B), from April 1995 to August 2006.
      Patients were divided into two groups; patients included in groups I and II
      received LRCCSs from surgeons A and B, respectively. RESULTS: The moving average
      method revealed that the operation times of surgeons A and B began to shorten
      after the 9th case. The cumulative sum (CUSUM) analysis of group I data showed
      that the 24th case was the peak point of conversion. The 35th case was the peak
      for intraoperative complications, and the 17th case was the peak for
      postoperative complications. There was only one case of conversion in group II.
      The peak points for inadequate lymph node dissection were the 37th case in group
      I and the 8th case in group II. The CUSUM analysis for surgeons A and B showed
      that the 18th case and the 8th case, respectively, were the overall peak points
      in the failure of LRCCS. CONCLUSIONS: We suggest that careful observation of a
      laparoscopic procedure, such as acting as the scope operator for a certain amount
      of time, may help in shortening the LC of the actual procedure.

PMID- 21854206
TI  - Transanal endoscopic microsurgery-based transanal access for colorectal surgery:
      experience on human cadavers.
AB  - Transanal endoscopic microsurgery (TEM) was described in 1983 for local excision
      of rectal tumors. In the context of natural orifice translumenal endoscopic
      surgery, we have modified the original TEM system and developed a new set of
      instruments. These are more curved and, in addition, steerable. After extensive
      studies in an ex-vivo model, we developed a novel technique for transanal
      rectosigmoid resection and colorectal anastomosis. The technique comprises
      closure of the rectal lumen by purse-string suture, transection of the rectal
      wall distal to the closure, circumferential mobilization of rectum and mesorectal
      tissue in the anatomical plane from below upward, control of the inferior
      mesenteric vessel, removal of mobilized colorectum through the anus, and,
      finally, the colorectal anastomosis by either stapled or hand-sutured technique.
      This procedure was performed on three alcohol-glycerol preserved well-built human
      cadavers (M:F=2:1). The average operating time was 190 minutes. The average
      length of the resected specimen was 23 cm. There was no fecal contamination or
      injury to the resected specimen. Postprocedure laparotomy revealed adequate
      mesorectal resection and no inadvertent injury to other viscera. During
      dissection in the pelvis, as the resected rectum was pushed upward, an
      unobstructed "empty pelvis" situation was developed in the operating site, thus
      facilitating the mesorectal resection. Transanal access for colorectal surgery
      seems feasible. It provides a precise definition of the distal safety margin,
      good view of the pelvis for meticulous mesorectal resection, and reduces the
      abdominal wall trauma. These may enhance the outcome of colorectal resection.
      However, further clinical studies can only substantiate these findings.

PMID- 21854207
TI  - Laser ablation of placental vessels in twin-to-twin transfusion syndrome: a
      paradigm for endoscopic fetal surgery.
AB  - Endoscopic fetal surgery is most commonly used for the treatment of twin-to-twin
      transfusion syndrome (TTTS), but the surgical techniques can be applied to other
      forms of fetal surgery. We present our experience with endoscopic fetal surgery
      over the past 10 years. From 2000 to 2010, 70 endoscopic laser ablations of
      placental vessels for TTTS were performed. Median number of placental vessels
      ablated was four. The incidence of preterm rupture of membranes (PROM) was 6%.
      Overall survival was 70%, with at least one twin surviving in 82%. Tocolysis was
      used in 73% of patients for a median of 12 hours. The combination of an open
      surgical approach, Seldinger technique, and uterine plugging led to outcomes
      similar to other reports, with a significantly lower PROM rate. Although TTTS is
      the most common application of endoscopic fetal surgery, this approach is
      applicable for other indications. Insertion and removal of tracheal occlusion
      balloons for severe congenital diaphragmatic hernia are currently being performed
      at our institution.

PMID- 21854208
TI  - The effect of stocking densities on reproductive performance in laboratory
      zebrafish (Danio rerio).
AB  - Despite the growing popularity of the zebrafish model system, the optimal
      husbandry conditions for this animal are not well defined. The aim of this study
      was to examine the effect of stocking density on reproductive performance in
      zebrafish. In this study, undertaken by eight different zebrafish facilities,
      clutches of at least 200 wild-type zebrafish embryos from a single pairwise
      mating were produced at each participating institution and subsequently reared
      according to "in-house protocols" until they were 14 weeks old. Fish were then
      randomly assigned into treatment groups with balanced sex ratios and densities of
      3, 6, or 12 fish/L. After a 1-month acclimation period, fish were spawned in pair
      crosses every 2 weeks for 3 months, for a total of six spawning dates. The number
      of viable and nonviable embryos produced in each clutch were counted at 1 day
      postfertilization. Although there was a great deal of variability in clutch size
      and percent spawning success among laboratories, there were no significant
      differences in average clutch size, spawning success, or percent viable among the
      treatment densities. These data suggest that using stocking densities as high as
      12 fish/L does not have a negative impact on performance, when measured by
      reproductive performance.

PMID- 21854209
TI  - Pentavalent arsenate transport by zebrafish phosphate transporter NaPi-IIb1.
AB  - Arsenate is a pentavalent form of arsenic that shares similar chemical properties
      to phosphate. It has been shown to be taken up by phosphate transporters in both
      eukaryotic and prokaryotic microbes such as yeast and Escherichia coli. Recently,
      the arsenate uptake in vertebrate cells was reported to be facilitated by
      mammalian type II sodium/phosphate transporter with different affinities. As
      arsenate is the most common form of arsenic exposure in aquatic system,
      identifying the uptake pathway of arsenate into aquatic animals is a crucial step
      in the elucidation of the entire metabolic pathway of arsenic. In this study, the
      ability of a zebrafish phosphate transporter, NaPi-IIb1 (SLC34a2a), to transport
      arsenate was examined. Our results demonstrate that a type II phosphate
      transporter in zebrafish, NaPi-IIb1, can transport arsenate in vitro when
      expressed in Xenopus laevis oocytes. NaPi-IIb1 mediates a high-affinity arsenate
      transport, with a K(m) of 0.22 mM. The natural substrate of NaPi-IIb1, dibasic
      phosphate, inhibits arsenate transport. Arsenate transport via NaPi-IIb1 is
      coupled with Na(+) and exhibits sigmoidal kinetics with a Hill coefficient of
      3.24 +/- 0.19. Consistent with these in vitro studies, significant arsenate
      accumulation is observed in all examined zebrafish tissues where NaPi-IIb1 is
      expressed, particularly intestine, kidney, and eye, indicating that zebrafish
      NaPi-IIb1 is likely the transport protein that is responsible for arsenic
      accumulation in vivo.

PMID- 21854210
TI  - Fasted zebrafish mimic genetic and physiological responses in mammals: a model
      for obesity and diabetes?
AB  - With worldwide rates of obesity and type-II diabetes increasing, it is essential
      to identify and understand the mechanisms involved during nutrient absorption and
      fuel allocation. Recent studies demonstrate that nutrients (e.g., lipids and
      carbohydrates) play a major regulatory role in gene transcription of glycolytic
      and lipogenic enzymes in addition to hormones, including insulin and glucagon.
      These nutrients generally exert their effects through key cellular
      nutrient/energy receptors. Fasting was used to identify these nutrient/energy
      receptors known from mammalian studies to ascertain if zebrafish (Danio rerio)
      are a suitable model for the study of metabolic disorders. Zebrafish were
      subjected to a fasting/re-feeding regime for 3 weeks, and gene expression of
      sterol responsive binding protein 1 and 2 (SREBP), the mammalian target of
      rapamycin (mTOR), cAMP response element binding protein 3-like 3 (CREB3l3), and
      AMP-activated protein kinase alpha (AMPKalpha) was assessed. Fasted zebrafish
      lost ~10% of their body mass over the 3-week experiment, with an associated
      depression in oxygen consumption. Increases in liver AMPKalpha and CREB3l3 mRNA
      transcript level were noted, concurrent with increases in the activities of the
      beta-oxidation and gluconeogenic markers beta-hydroxyacyl CoA dehydrogenase and
      phosphoenolpyruvate carboxykinase, respectively. Conversely, a depression in
      liver mTOR and SREBP1 and 2 expression was noted, with a decrease in pyruvate
      kinase and alanine aminotransferase activities and decreases in liver lipid and
      glycogen contents. Twenty-four hours after re-feeding, zebrafish rapidly recover,
      and the majority of parameters return to control values. Taken together, these
      data suggest adult zebrafish are an appropriate model for the further study of
      human metabolic disorders.

PMID- 21854212
TI  - MicroRNA-mediated processes are essential for the cellular radiation response.
AB  - A detailed understanding of the mechanisms that determine the variable cellular
      sensitivity to radiation is needed for improved radiation therapy as well as for
      the identification of individuals with innate radiation hypersensitivity.
      MicroRNAs (miRNAs) are a class of small non-coding RNAs that post
      transcriptionally regulate protein expression. Alterations in miRNA expression
      patterns in response to ionizing radiation have been shown, but there are almost
      no data describing the functional impact of these miRNA changes. We report here
      the results of studies on the functional roles of miRNAs in the radiation
      response in immortalized and primary endothelial cells. Global suppression of
      miRNA expression was achieved through downregulation of Argonaut e-2 (AGO2) or
      DICER proteins using RNAi. The reductions in either DICER or AGO2 led to
      increased cell death after irradiation, indicating a prosurvival function of
      miRNAs. Furthermore, while cell cycle checkpoint activation and apoptosis were
      compromised, DNA double-strand break repair was not affected by the lack of
      miRNAs. The differential sensitivity of these pathways implies the independent
      activation of the two response pathways rather than a concerted DNA damage
      response. The miRNAs that were changed after 2.5 Gy irradiation were identified
      by TaqMan-based low-density array technology. Of the miRNAs showing an
      upregulation 4 h or 24 h after radiation exposure, we were able to establish
      prosurvival and antiapoptotic functions for three miRNAs. Taken together, our
      data indicate a general prosurvival role for miRNA-mediated gene regulation
      during the radiation response. We show a functional association between miRNAs,
      apoptosis and cell cycle checkpoint activation in irradiated cells.

PMID- 21854211
TI  - Laminin 332 deposition is diminished in irradiated skin in an animal model of
      combined radiation and wound skin injury.
AB  - Skin exposure to ionizing radiation affects the normal wound healing process and
      greatly impacts the prognosis of affected individuals. We investigated the effect
      of ionizing radiation on wound healing in a rat model of combined radiation and
      wound skin injury. Using a soft X-ray beam, a single dose of ionizing radiation
      (10-40 Gy) was delivered to the skin without significant exposure to internal
      organs. At 1 h postirradiation, two skin wounds were made on the back of each
      rat. Control and experimental animals were euthanized at 3, 7, 14, 21 and 30 days
      postirradiation. The wound areas were measured, and tissue samples were evaluated
      for laminin 332 and matrix metalloproteinase (MMP) 2 expression. Our results
      clearly demonstrate that radiation exposure significantly delayed wound healing
      in a dose-related manner. Evaluation of irradiated and wounded skin showed
      decreased deposition of laminin 332 protein in the epidermal basement membrane
      together with an elevated expression of all three laminin 332 genes within 3 days
      postirradiation. The elevated laminin 332 gene expression was paralleled by an
      elevated gene and protein expression of MMP2, suggesting that the reduced amount
      of laminin 332 in irradiated skin is due to an imbalance between laminin 332
      secretion and its accelerated processing by elevated tissue metalloproteinases.
      Western blot analysis of cultured rat keratinocytes showed decreased laminin 332
      deposition by irradiated cells, and incubation of irradiated keratinocytes with
      MMP inhibitor significantly increased the amount of deposited laminin 332.
      Furthermore, irradiated keratinocytes exhibited a longer time to close an
      artificial wound, and this delay was partially corrected by seeding keratinocytes
      on laminin 332-coated plates. These data strongly suggest that laminin 332
      deposition is inhibited by ionizing radiation and, in combination with slower
      keratinocyte migration, can contribute to the delayed wound healing of irradiated
      skin.

PMID- 21854213
TI  - Expression of genes involved in mouse lung cell differentiation/regulation after
      acute exposure to photons and protons with or without low-dose preirradiation.
AB  - The goal of this study was to compare the effects of acute 2 Gy irradiation with
      photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure
      to low-dose/low-dose-rate gamma rays (0.01 Gy at 0.03 cGy/h), on 84 genes
      involved in stem cell differentiation or regulation in mouse lungs on days 21 and
      56. Genes with a >=1.5-fold difference in expression and P < 0.05 compared to 0
      Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors
      responsible for local tissue repair were also compared. Overall, striking
      differences were present between protons and photons in modulating the genes.
      More genes were affected by protons than by photons (22 compared to 2 and 6
      compared to 2 on day 21 and day 56, respectively) compared to 0 Gy.
      Preirradiation with low-dose-rate gamma rays enhanced the acute photon-induced
      gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly
      downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1,
      dll1, foxa2 and notch1) were upregulated in response to most of the radiation
      regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all
      radiation regimens. The number of alveolar type 2 cells positive for
      prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6
      cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these
      results showed that acute photons and protons induced different gene expression
      profiles in the lungs and that pre-exposure to low-dose-rate gamma rays sometimes
      had modulatory effects. In addition, proteins associated with lung-specific stem
      cells/progenitors were highly sensitive to radiation.

PMID- 21854214
TI  - Ero1alpha regulates Ca(2+) fluxes at the endoplasmic reticulum-mitochondria
      interface (MAM).
AB  - AIMS: The endoplasmic reticulum (ER) is involved in many functions, including
      protein folding, redox homeostasis, and Ca(2+) storage and signaling. To perform
      these multiple tasks, the ER is composed of distinct, specialized subregions,
      amongst which mitochondrial-associated ER membranes (MAM) emerge as key signaling
      hubs. How these multiple functions are integrated with one another in living
      cells remains unclear. RESULTS: Here we show that Ero1alpha, a key controller of
      oxidative folding and ER redox homeostasis, is enriched in MAM and regulates
      Ca(2+) fluxes. Downregulation of Ero1alpha by RNA interference inhibits
      mitochondrial Ca(2+) fluxes and modifies the activity of mitochondrial Ca(2+)
      uniporters. The overexpression of redox active Ero1alpha increases passive Ca(2+)
      efflux from the ER, lowering [Ca(2+)](ER) and mitochondrial Ca(2+) fluxes in
      response to IP3 agonists. INNOVATION: The unexpected observation that Ca(2+)
      fluxes are affected by either increasing or decreasing the levels of Ero1alpha
      reveals a pivotal role for this oxidase in the early secretory compartment and
      implies a strict control of its amounts. CONCLUSIONS: Taken together, our results
      indicate that the levels, subcellular localization, and activity of Ero1alpha
      coordinately regulate Ca(2+) and redox homeostasis and signaling in the early
      secretory compartment.

PMID- 21854215
TI  - Highlights of the second international conference on "Immunotherapy in Pediatric
      Oncology".
AB  - The Second International Conference on Immunotherapy in Pediatric Oncology was
      held in Houston, Texas, USA, October 11-12, 2010, to discuss the progress and
      challenges that have occurred in cutting edge immunotherapeutic strategies
      currently being developed for pediatric oncology. Major topics included immune
      targeting of acute lymphoblastic leukemia and pediatric solid tumors, chimeric
      antigen receptors (CARs) for hematologic malignancies and solid tumors, enhancing
      graft-versus-leukemia for pediatric cancers, overcoming hurdles of immunotherapy,
      strategies to active the innate immune system, and moving immunotherapy beyond
      phase I studies. Significant progress has been made in the last 2 years both in
      the development of novel immunobiologics such as CARs, and in establishing
      survival benefits of an anti-GD2 monoclonal antibody in randomized studies.
      Although there is much excitement going forward, a great deal of laboratory and
      regulatory challenges lie ahead in improving the efficacy of each of these
      modalities as well as getting them to patients in a timely and cost-effective
      fashion. The resulting discussions will hopefully lead to new collaborations and
      insight for further translational and clinical studies.

PMID- 21854216
TI  - Blood transfusion and alloimmunization in patients with thalassemia: multicenter
      study.
AB  - One of transfusion's side effects is alloimmunization against red blood cell
      (RBC) antigens. Early diagnosis by antibody screening is an important step in the
      detection of these alloantibodies. The authors studied the frequency of
      alloimmunization in thalassemic patients of 4 centers (2 adult and 2 pediatric
      centers) and compared the rates in children (up to 15 years) and adults. Antibody
      screening tests were performed by gel method according to its standard pattern
      and respective program. In positive cases, antibody identification test by gel
      method was performed. Eight hundred thirty-five patients were studied; 548
      (65.6%) were adults (mean age = 24.5), and 287 (34.4%) cases were pediatrics
      (mean age = 10.05). Of these patients, 74.1% had no history of transfusion
      reaction, whereas 21 (2.5%) had hemolytic complications. Seventy-eight (9.3%)
      exhibited allergic symptoms, and 117 (14%) cases experienced febrile reactions
      during transfusion. Antibody screening showed positive results in 22 pediatric
      cases (7.7%) and 79 adults (14.4%); 72 (71.3%), 19 (18.8%), 3 (3%), and 1 (1%)
      cases exhibited single, double, triple, and autoantibodies, respectively. Anti
      Kell antibody was seen in 34 (33.7%) cases, anti-D was seen in 11 (10.9%) cases,
      and anti-E in was seen in 10 (9.9%) cases. The authors observed 8 anti-D+C (7.9%)
      cases, 1 anti-D+E (1%), 3 anti-Kell+E, 3 anti-Kell+Kpa (3%), and 1 anti-Kell+D
      double antibodies. These antibodies were also a combination of Rh subgroups or Rh
      and Kell subgroups. The authors observed meaningful relations between history of
      transfusion reactions and age with antibody screening results (P = .005). Based
      on alloantibodies types, more than two thirds of them were Rh subgroups and Kell
      groups. Phenotype determination of RBCs before beginning chronic blood
      transfusion and careful cross-matching with Kell and Rh subgroups in addition to
      ABO may help reduce alloimmunization in chronic transfusion patients.

PMID- 21854218
TI  - Adjuvant effects of gaseous formaldehyde on the hyper-responsiveness and
      inflammation in a mouse asthma model immunized by ovalbumin.
AB  - Asthma is a complex pulmonary inflammatory disease, which is characterized by
      airway hyper-responsiveness, airflow obstruction, and airway inflammation.
      Exposure to a number of chemicals including formaldehyde (FA) can lead to asthma.
      This study aimed to explore the underlying role of FA exposure in occupational
      asthma, especially when it is combined with allergen exposure. Balb/c mice were
      randomly divided into six groups (n = 6/group): (1) saline control; (2) ovalbumin
      (OVA)-immunized (OVA(imm)) only; (3) 0.5 mg FA/m(3) exposure; (4) OVA(imm) + 0.5
      mg FA/m(3); (5) 3.0 mg FA/m(3) FA exposure; and, (6) OVA(imm) + 3.0 mg FA/m(3).
      These low and high exposure FA levels were adopted from current (0.5 mg/m(3)) and
      original (3.0 mg/m(3)) Chinese Occupational Threshold Limit Values. Experiments
      were conducted after 3 week of combined exposure and a 1-week challenge with
      aerosolized OVA. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil
      infiltration, and increased interleukin (IL)-4 and IL-6 levels in lung tissues
      were found in the OVA + 3.0 mg FA/m(3) hosts as compared to values seen in the
      OVA-immunized only mice. The results here suggest to us that FA exposure can
      induce and aggravate asthma in Balb/c mice when it is combined with OVA
      immunization.

PMID- 21854219
TI  - Kinetics of c-reactive protein (CRP) and serum amyloid A protein (SAA) in
      patients with community-acquired pneumonia (CAP), as presented with biologic half
      life times.
AB  - Context: In management of community-acquired pneumonia (CAP), excellent
      biomarkers for inflammation would be helpful in our practice. Objectives:
      Kinetics of c-reactive protein (CRP) and serum amyloid A (SAA) was characterized,
      using their biologic half-life times. Materials and methods: Time course of CRP
      and SAA levels in the successfully treated 36 CAP patients were investigated and
      their half-life times were determined and compared. Results & Discussions: SAA
      and CRP declined in an exponential mean and the biologic half-life times of SAA
      levels was 34.9 +/- 28.7 h, significantly shorter than that of CRP, 46.4 +/- 21.7
      h (p = 0.0014). Conclusion: The kinetic evidence, presented as biologic half-life
      times of CRP and SAA, helps us make a clinical assessment of CAP patients.

PMID- 21854220
TI  - Prevalence of Neospora caninum antibodies in sheep and goats in Pakistan.
AB  - The purpose of the present study was to obtain seroepidemiological information on
      the Neospora caninum infection status of sheep and goats in different areas of
      Punjab Province and Azad Kashmir (Pakistan). A cross-sectional study, with the
      use of a competitive ELISA, showed an overall 27.7% (35 of 128) (95% confidence
      interval [CI] +/- 7.7%) and 8.6% (13 of 142) (95% CI +/- 4.6%) seroprevalence of
      N. caninum antibodies in sheep and goats, respectively. The difference in
      seroprevalence between sheep and goat populations was statistically significant
      (P < 0.05). The highest prevalence (37.4% +/- 13.2%) was recorded in the tailless
      breed of sheep.

PMID- 21854222
TI  - Limited midwifery care for undocumented women in the Netherlands.
AB  - BACKGROUND: Ethnic minority women in Western countries have poorer pregnancy
      outcomes compared to majority populations, and undocumented women are
      particularly vulnerable. We intended to assess whether midwives adjust their care
      if women are undocumented and have no health insurance. METHODS: A retrospective
      matched cohort study in primary midwifery care practices in Amsterdam and
      Rotterdam, the Netherlands. Undocumented, uninsured women (N?=?141) were matched
      with documented, insured ethnic minority women (N?=?141). Information was
      extracted from patient records. RESULTS: Undocumented women attended their first
      prenatal visit 5 weeks later in their pregnancy and received care elsewhere or
      disappeared from care more frequently (59.6 versus 34.3%). They frequently have
      an excess of 110% of the number of expected antenatal visits (32.4% versus 16.9%)
      and had a preterm birth more frequently (OR 4.59, 95% CI 1.43 to 14.72). Midwives
      were equally likely to follow referral guidelines in both groups. Undocumented
      women were more likely to give birth at home (OR 2.14, 95% CI 1.07?4.28) and less
      likely to receive maternity home care assistance (56.0 versus 79.7%). CONCLUSION:
      Although referral guidelines are generally followed by midwives, undocumented
      women are more at risk of adverse perinatal outcomes and inadequate care than
      documented ethnic minority women.

PMID- 21854221
TI  - Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of
      select mediators of inflammation in human monocytic cells.
AB  - Bresol-a poly-herbal formulation, has been reported to be effective against
      bronchial asthma and allergic rhinitis in children. In vivo studies have
      supported the anti-histaminic and anti-anaphylactic action of bresol. However,
      the mechanism of action of bresol in modulation of inflammation has not been
      studied at the cellular and molecular level. The present study was aimed to
      elucidate the mechanism(s) of action of bresol at the cellular and molecular
      levels, using human monocyte leukemia cells. The effects of bresol on
      phosphodiesterase 4B (PDE4B) gene expression were analyzed using human monocytic
      U937 leukemia cells. The ability of bresol to stimulate cAMP formation in these
      cells, as well as its effects on mediators of inflammation like tumor necrosis
      factor-alpha (TNFalpha), nitric oxide (NO), and cycloxygenase-2 (COX-2) in
      lipopolysaccharide (LPS)-stimulated U937 cells, were also studied. The results
      here indicated that bresol exhibited potential anti-inflammatory properties by
      inhibiting LPS-induced PDE4B gene expression in the cells. Bresol also dose
      dependently activated cAMP formation, and inhibited TNFalpha, NO, as well as COX
      2 formation in the LPS-stimulated cells. Based upon the results, we concluded
      that the reported anti-inflammatory activity of bresol might be attributed to its
      abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes. The
      anti-inflammatory effects of bresol might also be a result of the capacity of
      bresol to modulate the formation of TNFalpha, NO, and COX-2 in monocytes.

PMID- 21854223
TI  - Antimycobacterial activity of 2-phenoxy-1-phenylethanone, a synthetic analogue of
      neolignan, entrapped in polymeric microparticles.
AB  - Conventional treatment of tuberculosis (TB) demands a long course therapy (6
      months), known to originate multiple drug resistant strains (MDR-TB), which
      emphasizes the urgent need for new antituberculous drugs. The purpose of this
      study was to investigate a novel treatment for TB meant to improve patient
      compliance by reducing drug dosage frequency. Polymeric microparticles containing
      the synthetic analogue of neolignan, 1-phenyl-2-phenoxiethanone (LS-2), were
      obtained by a method of emulsification and solvent evaporation and chemically
      characterized. Only representative LS-2-loaded microparticles were considered for
      further studies involving experimental murine TB induced by Mycobacterium
      tuberculosis H37Rv ATCC 27294. The LS-2-loaded microparticles were spherical in
      shape, had a smooth wall and showed an encapsulation efficiency of 93% in
      addition to displaying sustained release. Chemotherapeutic potential of LS-2
      entrapped in microparticles was comparable to control groups. These findings are
      encouraging and indicate that LS-2-loaded microparticles are a potential
      alternative to conventional chemotherapy of TB.

PMID- 21854224
TI  - An examination of online health information seeking by deaf people.
AB  - Research indicates that information seekers often turn to the Internet for health
      information; however, little is known about how Deaf people perceive, access, and
      utilize the Internet as a health information source. In this study, eight focus
      groups with Deaf participants (n = 39) were conducted to explore how Deaf people
      make use of (or avoid) the Internet as a health information source. Focus-group
      transcripts were analyzed using latent content and constant comparative
      techniques. Findings are presented using the model of online health information
      seeking and illustrate the reasons reported for both avoiding and utilizing the
      Internet as a health information source. In addition, findings illustrate the
      processes Deaf people navigate when accessing online health information, as well
      as the strategies they employ when doing so. This research underscores the need
      for continued investigation of access to and use of e-health resources by Deaf
      people.

PMID- 21854225
TI  - Inoculation's efficacy with young adults' risky behaviors: can inoculation confer
      cross-protection over related but untreated issues?
AB  - This investigation examined the potential of inoculation to protect young adults'
      attitudes from pressures to engage in risky behaviors (unprotected sex and binge
      drinking) as well as inoculation's efficacy in conferring umbrella protection
      (cross-protection) over related, but experimentally untreated, attitudes. A three
      phase experiment was conducted involving 120 participants. The results revealed
      that inoculation can protect the attitudes of young adults from
      counterattitudinal pressures to engage in unprotected sex (treated issue) and
      binge drinking (untreated issue). Practical applications of these findings are
      explored, including the use of inoculation when designing health messages and
      more thorough assessments of health campaigns designed to discourage risky
      behaviors.

PMID- 21854226
TI  - Love and hooking up in the new millennium: communication technology and
      relationships among urban African American and Puerto Rican young adults.
AB  - Communication technology is a central feature of young people's lives, but its
      role in romantic and sexual relationships has not been thoroughly examined. This
      article describes how young adults use communication technology for partnering
      across relationship stages (formation, maintenance, and dissolution) and types
      (serious/casual), and proposes implications of usage in relationships. This study
      analyzed qualitative data from a five-week, prospective, coital diary method with
      related debriefing interviews (N = 70) of African American and Puerto Rican men
      and women aged 18 to 25 years in Hartford and Philadelphia. Cell phones,
      including calls, text messaging, and mobile Internet, were the most common forms
      of communication technology used for partnering goals. Participants reported
      using cell phones to pursue partnering goals across all relationship stages,
      including formation (meeting, screening, and getting to know new partners),
      maintaining existing relationships, and breaking up. Cell phone uses depended on
      the type of relationship (serious/casual) and the participants' intentions and
      desires. Results indicated that cell phones are an important element of
      communication among young adults in romantic and sexual relationships. Specific
      features of cell phone communication shape the process and context of partnering.
      Future research should explore emerging communication technologies and
      implications for psychosocial development, dating violence, and sexual behavior.

PMID- 21854227
TI  - Chronic pain states: pharmacological strategies to restore diminished inhibitory
      spinal pain control.
AB  - Potentially noxious stimuli are sensed by specialized nerve cells named
      nociceptors, which convey nociceptive signals from peripheral tissues to the
      central nervous system. The spinal dorsal horn and the trigeminal nucleus serve
      as first relay stations for incoming nociceptive signals. At these sites,
      nociceptor terminals contact a local neuronal network consisting of excitatory
      and inhibitory interneurons as well as of projection neurons. Blockade of
      neuronal inhibition in this network causes an increased sensitivity to noxious
      stimuli (hyperalgesia), painful sensations occurring after activation of non
      nociceptive fibers (allodynia), and spontaneous pain felt in the absence of any
      sensory stimulation. It thus mimics the major characteristics of chronic pain
      states. Diminished inhibitory pain control in the spinal dorsal horn occurs
      naturally, e.g., through changes in the function of inhibitory neurotransmitter
      receptors or through altered chloride homeo-stasis in the course of inflammation
      or nerve damage. This review summarizes our current knowledge about endogenous
      mechanisms leading to diminished spinal pain control and discusses possible ways
      that could restore proper inhibition through facilitation of fast inhibitory
      neurotransmission.

PMID- 21854228
TI  - The expression and function of organic anion transporting polypeptides in normal
      tissues and in cancer.
AB  - Organic anion transporting polypeptides (OATPs) are members of the SLCO gene
      superfamily of proteins. The 11 human OATPs are classified into 6 families and
      subfamilies on the basis of their amino acid sequence similarities. OATPs are
      expressed in several epithelial tissues throughout the body and transport mainly
      amphipathic molecules with molecular weights of more than 300 kDa. Members of the
      OATP1 and OATP2 families are functionally the best-characterized OATPs. Among
      these are the multispecific OATP1A2, OATP1B1, OATP1B3, and OATP2B1. They
      transport various endo- and xenobiotics, including hormones and their conjugates
      as well as numerous drugs such as several anticancer agents. Recent reports
      demonstrate that some OATPs are up- or downregulated in several cancers and that
      OATP expression might affect cancer development. On the basis of the findings
      summarized in this review, we propose that OATPs could be valuable targets for
      anticancer therapy.

PMID- 21854229
TI  - Human copy number variation and complex genetic disease.
AB  - Copy number variants (CNVs) play an important role in human disease and
      population diversity. Advancements in technology have allowed for the analysis of
      CNVs in thousands of individuals with disease in addition to thousands of
      controls. These studies have identified rare CNVs associated with
      neuropsychiatric diseases such as autism, schizophrenia, and intellectual
      disability. In addition, copy number polymorphisms (CNPs) are present at higher
      frequencies in the population, show high diversity in copy number, sequence, and
      structure, and have been associated with multiple phenotypes, primarily related
      to immune or environmental response. However, the landscape of copy number
      variation still remains largely unexplored, especially for smaller CNVs and those
      embedded within complex regions of the human genome. An integrated approach
      including characterization of single nucleotide variants and CNVs in a large
      number of individuals with disease and normal genomes holds the promise of
      thoroughly elucidating the genetic basis of human disease and diversity.

PMID- 21854230
TI  - V(D)J recombination: mechanisms of initiation.
AB  - V(D)J recombination assembles immunoglobulin and T cell receptor genes during
      lymphocyte development through a series of carefully orchestrated DNA breakage
      and rejoining events. DNA cleavage requires a series of protein-DNA complexes
      containing the RAG1 and RAG2 proteins and recombination signals that flank the
      recombining gene segments. In this review, we discuss recent advances in our
      understanding of the function and domain organization of the RAG proteins, the
      composition and structure of RAG-DNA complexes, and the pathways that lead to the
      formation of these complexes. We also consider the functional significance of RAG
      mediated histone recognition and ubiquitin ligase activities, and the role played
      by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination.
      Finally, we propose a model for the formation of RAG-DNA complexes that involves
      anchoring of RAG1 at the recombination signal nonamer and RAG2-dependent
      surveillance of adjoining DNA for suitable spacer and heptamer sequences.

PMID- 21854231
TI  - High-resolution imaging of selenium in kidneys: a localized selenium pool
      associated with glutathione peroxidase 3.
AB  - AIM: Recent advances in quantitative methods and sensitive imaging techniques of
      trace elements provide opportunities to uncover and explain their biological
      roles. In particular, the distribution of selenium in tissues and cells under
      both physiological and pathological conditions remains unknown. In this work, we
      applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map
      selenium distribution in mouse liver and kidney. RESULTS: Liver showed a uniform
      selenium distribution that was dependent on selenocysteine tRNA([Ser]Sec) and
      dietary selenium. In contrast, kidney selenium had both uniformly distributed and
      highly localized components, the latter visualized as thin circular structures
      surrounding proximal tubules. Other parts of the kidney, such as glomeruli and
      distal tubules, only manifested the uniformly distributed selenium pattern that
      co-localized with sulfur. We found that proximal tubule selenium localized to the
      basement membrane. It was preserved in Selenoprotein P knockout mice, but was
      completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice,
      indicating that this selenium represented GPx3. We further imaged kidneys of
      another model organism, the naked mole rat, which showed a diminished uniformly
      distributed selenium pool, but preserved the circular proximal tubule signal.
      INNOVATION: We applied XFM to image selenium in mammalian tissues and identified
      a highly localized pool of this trace element at the basement membrane of kidneys
      that was associated with GPx3. CONCLUSION: XFM allowed us to define and explain
      the tissue topography of selenium in mammalian kidneys at submicron resolution.

PMID- 21854233
TI  - Steps towards empowerment: an examination of colleges, health services and
      universities.
AB  - In Australia, nursing educators work across three main contexts - training
      colleges, health services and universities. Because the pace of change for
      nursing has increased dramatically and the curriculum is becoming even more
      crowded, educators in these contexts are likely to be experiencing work-related
      stress. This study investigated this issue utilising a purposive sampling
      strategy to interview a cross section of nurse educators and those supporting
      educators. Eighteen in-depth interviews were completed, which included fourteen
      nurse educators and four key stakeholders. Qualitative analysis revealed that
      regardless of context, nurse educators found their role rewarding but there are
      common challenges. These included: Work role pressures, a non-validating culture,
      the pace of change, isolation and concern for the profession. There are also
      differences amongst the cohorts. Finally, participants elaborated on specific
      solutions to these problems and there is strong support for the establishment of
      a national community of practice to bring diverse educators together to share,
      support, extend and evaluate each others' work.

PMID- 21854232
TI  - Immune activation in the pathogenesis of treated chronic HIV disease: a workshop
      summary.
AB  - With the advent of highly effective antiretroviral therapy (ART), infection with
      human immunodeficiency virus (HIV) has become a chronic disease rather than a
      death sentence. Nevertheless, effectively treated individuals have a higher than
      normal risk for developing noninfectious comorbidities, including cardiovascular
      and renal disease. Although traditional risk factors of aging as well as
      treatment toxicity contribute to this risk, many investigators consider chronic
      HIV-associated inflammation a significant factor in such end-organ disease.
      Despite effective viral suppression, chronic inflammation persists at levels
      higher than in uninfected people, yet the stimuli for the inflammation and the
      mechanism by which inflammation persists and promotes disease pathology remain
      incompletely understood. This critical gap in scientific understanding
      complicates and hampers effective decision making about appropriate medical
      intervention. To better understand the mechanism(s) of chronic immune activation
      in treated HIV disease, three questions need answers: (1) what is the cause of
      persistent immune activation during treated HIV infection, (2) what are the best
      surrogate markers of chronic immune activation in this setting, and (3) what
      therapeutic intervention(s) could prevent or reverse this process? The NIH
      sponsored and convened a meeting to discuss the state of knowledge concerning
      these questions and the best course for developing effective therapeutic
      strategies. This report summarizes the findings of that NIH meeting.

PMID- 21854234
TI  - Knowledge and positions on bioethical dilemmas in a sample of Spanish nursing
      students: a questionnaire study.
AB  - This study, performed in Madrid, Spain, evaluates nursing students' understanding
      and attitudes about bioethical dilemmas that they will likely confront as health
      care providers. We asked 86 juniors in the King Juan Carlos University Nursing
      baccalaureate program about their knowledge of and personal attitudes on five
      biomedical advances: eugenics, experimentation with unimplanted embryos, human
      cloning, abortion, and euthanasia. Students reported being most knowledgeable
      about abortion and euthanasia and least familiar with eugenics. Examining the
      data for a correlation between the two phenomenon (knowledge and position) with
      respect to each of these five biomedical issues, the students reported
      significantly Conversely, they held significantly neutral positions on eugenics,
      a virtually unfamiliar topic for them (r = 0.618, p < 0.0001). The data also
      revealed a significantly direct correlation between knowledge and position for
      experimentation with non-implanted embryos (correlation coefficient = 0.380, p <
      0.0001), that is, little knowledge and neutral attitudes. The trend findings for
      abortion and cloning were not significant. Based on these data, we concluded that
      the nursing program would benefit from additional biomedical curriculum.

PMID- 21854235
TI  - Factors associated with learning outcome of BSN in a blended learning
      environment.
AB  - This paper is a report of a study to examine the influence of demographic,
      learning behavior and learning performance variables on learning outcomes of
      baccalaureate nursing students within a blended learning environment. A cross
      sectional survey was conducted using the self-structured demographic
      questionnaire, case analysis attitude scale (CAAS), the case analysis self
      evaluation scales (CASES), the metacognition scale (MS) and blended learning
      satisfaction scale (BLSS) to measure learning outcomes after the blended learning
      course. A total of 99 senior undergraduate nursing students currently studying at
      a public nursing college in Taiwan were eligible to participate in the study in
      2008. Data were analyzed by descriptive statistics and multiple linear
      regression. Univariate analysis showed significant associations between frequency
      of online dialogues, time spent on the internet, CAAS, and MS and scores on the
      ethical course. However, frequency of online dialogues, time spent on the
      internet, and the CAAS were significantly independent predictors for scores on
      the ethical course in the final model of multivariate analysis. The final model
      of the data analysis could account for 78% variances scores of ethical course
      (R(2) = 0.78 and adjusted R(2) = 0.77). It can be concluded from this study that
      frequency of online dialogue, time spent on internet, and the CAAS score are all
      useful predictors for learning outcome. In addition, blended learning was found
      to have contributed to learners' learning outcome by facilitating their
      metacognitive development and self-regulatory development. In blended learning
      courses, students have more responsibilities placed upon them than in traditional
      face-to-face learning environments. The first step of constructing a working
      blended learning model is to develop student-oriented teaching pedagogies that
      include face-to-face and online instruction, rather than just focusing on the
      provision of technical skills.

PMID- 21854237
TI  - Factors impacting on career progression for nurse executives.
AB  - This discursive paper examines recent research on career progression for nurse
      executives in Australia. In particular, it focuses on the personal, work-related
      and professional factors which influence progression. The role of gender,
      location and the provision of mentoring are also considered. It is suggested that
      family friendly policies (such as the option to job share or to perform an
      executive role on a part-time basis), the availability of a mentor, and the
      opportunity to pursue further education/training are vital in assisting nurses to
      progress in their executive careers.

PMID- 21854236
TI  - Burden versus benefit: continuing nurse academics' experiences of working with
      sessional teachers.
AB  - Sessional teachers are taking an increasing role in classroom teaching in Schools
      of Nursing. However, there is a paucity of literature reporting the experiences
      of, and impact on, career academics working with or alongside the burgeoning
      numbers of sessional teachers. Therefore, the purpose of this paper is to explore
      the experiences of continuing academics working with sessional teachers. This
      qualitative study used purposive sampling to recruit nurse academics and collect
      narrative data related to their experiences of working with sessional teachers.
      Four major themes emerged from the data, namely: They have got real credibility -
      perceptions of clinical currency, We've got people who are very good clinically,
      but don't know how to teach - lacking skills and confidence, No allegiance to the
      school or the students - perceived lack of commitment and accountability, and A
      terrible burden - workload implications for continuing academics. The development
      and implementation of standards for the recruitment and employment of sessional
      teachers would benefit both continuing academics and sessional teachers, and
      assist in the delivery of quality teaching and learning to nursing students.

PMID- 21854238
TI  - Retention of indigenous nursing students in New Zealand: a cross-sectional
      survey.
AB  - Internationally the recruitment and retention of Indigenous and minority peoples
      into nursing is a persistent challenge, despite their participation being
      essential in reducing health disparities and improving health service quality for
      Indigenous and minority users. We aimed to identify Maori (Indigenous to New
      Zealand) nursing students' experiences of undertaking a nursing degree program. A
      non-experimental cross-sectional survey was undertaken with undergraduate nursing
      students identifying as Maori. The surveys were analyzed using descriptive and
      inferential statistics. One hundred and eight students responded, with a career,
      stable income, and desire to make a difference in Maori health outcomes
      motivating most to embark on a nursing program. They reported numerous obstacles
      that compromised their academic advancement. However, affirming students'
      identities; providing academic support; accessing Indigenous role models, mentors
      and relevant clinical experiences; and, having supportive teaching and learning
      environments and the inclusion of Indigenous content in curricula; were
      identified as strategies that promoted retention in nursing programs.

PMID- 21854239
TI  - Undergraduate midwifery students' first experiences with stillbirth and neonatal
      death.
AB  - While midwifery practice predominantly deals with happy experiences, unexpected
      and unpredictable events occur. This paper reports on a study that explored
      undergraduate midwifery students' first experiences of stillbirth and neonatal
      death. It sought to better understand their encounters to ensure curricula were
      responsive to students' needs. Semi-structured interviews were conducted with
      eight Bachelor of Midwifery students. Many were found to have been exposed to
      perinatal death early in their courses and were ill prepared for the
      confrontations. Furthermore, the existence of support services was varied.
      Dealing with these experiences appears to occur through a developmental process
      and resonates with previous research around compassion, fatigue and posttraumatic
      stress disorder. Overall, students require specific preparation prior to
      undertaking placements, as well as clearly identified support strategies if such
      experiences are encountered.

PMID- 21854240
TI  - Linguistic diversity as sociodemographic predictor of nursing program progression
      and completion.
AB  - Attrition from undergraduate nursing programs continues to warrant investigation
      particularly in the climate of nursing shortages and fiscal reflection on
      academic institutional programs. This three-year study used a prospective
      longitudinal survey design to determine entry characteristics of students,
      attrition, progression and completion in an undergraduate program. Students were
      surveyed in the first three weeks of commencing their program and gave permission
      for academic grades to be collected during their six session, three year Bachelor
      of Nursing program. Of the 740 students enrolled 48% (357 students) were surveyed
      and 352 students (99%) gave consent for their grades to be collected. One-third
      of the student cohort graduated in the expected three-year timeframe, one-third
      had dropped out and one-third was still completing their studies. A higher Grade
      Point Average and being a native English speaker were most predictive of students
      completing their course in the minimum expected timeframe.

PMID- 21854241
TI  - Enhancing preparation of undergraduate students for practice in older adult
      settings.
AB  - AIM: The aim of this study was to explore what factors may enhance the teaching
      and preparation of undergraduate Bachelor of Nursing students to better prepare
      them for practice in older adult settings in a provincial region of New Zealand.
      BACKGROUND: There are concerning shortages of nurses working in older adult
      settings in New Zealand. With an ageing nursing workforce, demand for nurses in
      this area will continue. Of ongoing concern is a lack of interest among
      undergraduate students to take up positions in older adult settings on completion
      of their studies. METHOD: This exploratory study utilised a qualitative approach
      to explore the perspectives of 12 participants (six faculty and six industry
      leaders) on how preparation of undergraduate students to take up nursing
      positions in the older adult sector can be enhanced. Data were collected over a 5
      month period from February 2009 until June 2009. FINDINGS: Ways to enhance
      undergraduate student preparation to work in the older adult sector included:
      making older adult content visible within an integrated curriculum; faculty
      development; identification of key skills and implementing processes to teach
      these; reinvigorating clinical placements in older adult settings with a
      particular focus at each year of the programme; and actively developing
      collaborative partnerships between faculty and clinicians. CONCLUSION: The
      provision of appropriate older adult care content in undergraduate registered
      nursing programmes is an area warranting attention if faculty are to ensure
      student nurses are appropriately prepared to take up positions in the older adult
      sector.

PMID- 21854242
TI  - Mature age students access, entry and success in nurse education: an action
      research study.
AB  - This action research study involved an 'expert group' that was convened to
      consider issues for mature age nursing students in the Australian context and
      develop recommendations that could be used to strengthen mature age entry, access
      and success in nursing programs. Consistent with action research, the group
      worked through phases of planning, action, observation, evaluation and critical
      reflection. In developing recommendations that could be used for future planning,
      the group met regularly, reviewed extensive literature, and conducted two data
      collection activities, a questionnaire and focus group with education providers.
      From the action research activities, five major recommendations were generated.
      These focused on the value of mature age students, the need for specific
      information, transparent and clear processes for students entering nurse
      education, study support and finally, the provision of financial assistance.

PMID- 21854243
TI  - Using an interdisciplinary partnership to develop nursing students' information
      literacy skills: an evaluation.
AB  - As learning paradigms shift to student-centred active learning, development of
      effective skills in locating and retrieving information using electronic sources
      is integral to promoting lifelong learning. Recency of information that is
      evidence based is a critical factor in a dynamic field such as health. A changing
      demographic is evident among nursing students with greater numbers of mature age
      students who may not possess the computer skills often assumed with school
      leavers, and whose study preference is mostly by external mode. Development of
      interdisciplinary partnerships between faculties and librarians can provide the
      attributes and innovation of new and improved ways to better support student
      learning, whether or not students attend on campus. The Health Online Tutorial,
      an online database searching tool developed through a collaborative,
      interdisciplinary partnership at Charles Darwin University is one such example.

PMID- 21854244
TI  - Evaluating an academic writing program for nursing students who have English as a
      second language.
AB  - Academic writing skills are essential to the successful completion of
      preregistration nursing programs, yet the development of such skills is a
      challenge for many nursing students, particularly those who speak English as a
      second language (ESL). It is vital to develop and evaluate strategies that can
      support academic writing skills for ESL nursing students. This qualitative study
      evaluated a four-day academic writing intervention strategy designed to support
      ESL first-year nursing students. Data from the program showed two major areas of
      difficulty for participants relating to academic writing: problems understanding
      course content in English, and problems expressing their understanding of that
      content in English. The participants noted a key benefit of this program was the
      provision of individual feedback. Programs such as this intervention successfully
      meet the demands of ESL nursing students, although ongoing support is also
      needed.

PMID- 21854245
TI  - Concerns among first year midwifery students: towards addressing attrition rates.
AB  - Since 2000, there has been a shift to undergraduate midwifery education in
      Australia. Midwifery students are generally highly motivated, however attrition
      rates remain high among first-year students. This study was undertaken in one
      Australian University against a background of high course demand and high student
      attrition. Thirty-two first-year midwifery students completed a demographic
      questionnaire and wrote a reflection in response to the question: What if
      anything, would make your experience as a first year student better? Data were
      subjected to thematic content analysis. Findings indicated a need for: greater
      opportunities to prepare; for more time to study; for greater student supports;
      and outlined difficulties such as financial and childcare. In conclusion,
      undergraduate midwifery courses and local conditions vary among institutions.
      Student feedback is a useful way of identifying local concerns that may impact on
      student completion rates. This is a necessary first step to the provision of
      meaningful student support.

PMID- 21854246
TI  - Doctorates and nurses.
AB  - There is a plethora of routes to obtaining a doctorate in nursing and this arises
      due to international differences in the modes of study, preparation of the final
      submission and examination systems. The variety of pathways and outcomes leads to
      some confusion over the status and purpose of doctorates in nursing. In this
      discursive paper we review the historical development of the doctorate in nursing
      and describe the various routes to doctorate in Europe, Australia and the United
      States. There is much in common between the various routes with increasing
      evidence of formal elements across the countries studies and, especially in the
      United Kingdom and the United States, evidence that the fitness for purpose of
      the doctorate in nursing is being examined and changes being introduced.

PMID- 21854247
TI  - Determining frameworks for interprofessional education and core competencies
      through collaborative consultancy: the CARE experience.
AB  - It is claimed that an interprofessional approach to health care aims to provide
      optimal client care, reduce duplication of services, address gaps in service
      delivery and prevent adverse consequences to patients. Hence there is widespread
      international interest in interprofessional education in undergraduate programs.
      However, after employment in the Australian health care workforce, there is
      limited opportunity for this. The continued education and training of health
      professionals and other care workers frequently occurs in a climate where
      professional development is dominated by the existence of professional
      demarcations. In order to enhance interprofessional collaboration in health care
      practice and education, mechanisms to guide individual performance within a multi
      professional health team are required. This paper presents both the process and
      outcomes of a consultancy undertaken in order to determine core competencies for
      collaborative interprofessional practice in a community and aged care service.

PMID- 21854248
TI  - Practical advice to support mid-career doctoral students in nursing: some
      considerations for academic supervisors.
AB  - Mid-career students who undertake doctoral studies have often achieved standing
      and success in their careers and may already hold quite senior leadership
      positions in the profession. In view of this, mid-career students may struggle
      with the transition to student, particularly if they have not studied for a
      number of years and have multiple pressures on their time. Supervisors on the
      other hand, operate within cultures of performance based indicators, and are
      under pressure to facilitate timely student completions. While students must take
      ultimate responsibility for their doctoral work, it is possible for supervisors
      to identify problems early, and offer practical solutions to assist mid-career
      students overcome their problems, and facilitate optimal engagement. In this
      paper we highlight some of the challenges this vulnerable student group can
      present, and identify some practical strategies supervisors can suggest to assist
      in the timely and successful completion of doctorate degrees.

PMID- 21854249
TI  - Evaluation of a critical care simulation series for undergraduate nursing
      students.
AB  - Simulation is increasingly being used to prepare and supplement clinical practice
      in critical care areas for undergraduate Bachelor of Nursing (BN) students, with
      some success. However, the effects of multiple, medium-high fidelity simulations
      for this purpose have not been previously assessed. The purpose of this study was
      to assess self-reported confidence and competence using scenario-based
      simulations. A pre-test post-test design was used to evaluate a series of
      simulations conducted over a semester. There were twenty seven scenarios,
      incorporating programmed mannequins, moulage and actors. The scenarios were
      embedded in a team-based process involving preparation and video-recordings used
      for debriefing. Third year BN students reported their confidence and competence
      before and after the simulation series and made comments on their perception of
      the experience. Multiple scenario simulations are effective in improving BN
      students' confidence and competence related to critical care practice and are an
      enjoyable experience for students.

PMID- 21854250
TI  - The transition experience of Enrolled Nurses to a Bachelor of Nursing at an
      Australian university.
AB  - Endorsed Enrolled Nurses (EENs) articulating from diploma level to Bachelor of
      Nursing (BN) studies at university experience many transitional barriers.
      Flexible credit arrangements can create further difficulties because students may
      enter directly into the second year of a degree program, thus foregoing
      supportive interventions targeting first year students. This qualitative study
      explored the transitional barriers faced by EENs articulating to the second year
      of a BN program and the processes employed to adapt to the university learning
      environment. Lizzio's (2006) Five Senses of Success Model provided a framework
      for data analysis. Lizzio's model highlights how students' success at university
      depends on their sense of purpose, capability, resourcefulness, connectedness and
      academic culture. This study revealed EENs grapple with their dual identity, have
      difficulty reconciling their academic and clinical competence, and struggle to
      assimilate to the academic learning environment. Findings illuminate the
      importance of tailoring orientation and engagement activities to the specific
      transitional needs of articulating students.

PMID- 21854251
TI  - Preformulation stability study of the EGFR inhibitor HKI-272 (Neratinib) and
      mechanism of degradation.
AB  - The stability in solution of HKI-272 (Neratinib) was studied as a function of pH.
      The drug is most stable from pH 3 to 4, and degradation rate increases rapidly
      around pH 6 and appears to approach a maximum asymptotic limit in the range of pH
      812. Pseudo first-order reaction kinetics was observed at all pH values. The
      structure of the major degradation product indicates that it is formed by a
      cascade of reactions within the dimethylamino crotonamide group of HKI-272. It is
      assumed that the rate-determining step is the initial isomerization from allyl
      amine to enamine functionality, followed by hydrolysis and subsequent cyclization
      to a stable lactam. The maximum change in degradation rate as a function of pH
      occurs at about pH 6, which corresponds closely to the theoretical pKa value of
      the dimethylamino group of HKI-272 when accounting for solvent/temperature
      effects. The observed relationship between pH and degradation rate is discussed,
      and a self-catalyzed mechanism for the allylamine-enamine isomerization reaction
      is proposed. The relevance of these findings to other allylamine drugs is
      discussed in terms of the relative stability of the allylic anion intermediate
      through which, the isomerization occurs.

PMID- 21854252
TI  - Physical characterization and cellular uptake of propylene glycol liposomes in
      vitro.
AB  - In order to facilitate the intracellular delivery of therapeutic agents, a new
      type of liposomes-propylene glycol liposomes (PGL) were prepared, and their cell
      translocation capability in vitro was examined. PGL was composed of hydrogenated
      egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a
      model drug, characterization of loaded PGL were measured including surface
      morphology, particle size, elasticity, encapsulation efficiency of curcumin and
      physical stability. Using curcumin-loaded conventional liposomes as the control,
      the cell uptake capacity of loaded PGL was evaluated by detection the
      concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL
      exhibited such advantages as high encapsulation efficiency (92.74% +/- 3.44%),
      small particle size (182.4 +/- 89.2 nm), high deformability (Elasticity index =
      48.6) and high stability both at normal temperature (about 25 degrees C) and low
      temperature at 4 degrees C. From cell experiment in vitro, PGL exhibited the
      highest uptake of curcumin compared with that of conventional liposomes and free
      curcumin solution. Little toxic effect on cellular viability was observed by
      methyl tetrazolium assay. In conclusion, PGL might be developed as a promising
      intracellular delivery carrier for therapeutic agents.

PMID- 21854254
TI  - Association between saliva PSA and serum PSA in conditions with prostate
      adenocarcinoma.
AB  - In recent years, saliva samples have attracted attention as specimens, which may
      be used for cancer diagnosis. Prostate-specific antigen (PSA) is the most useful
      tumor marker for prostate adenocarcinoma (PA). We examined whether there is an
      association between saliva PSA and serum PSA in patients with PA using enzyme
      linked immunosorbent assay. Human subjects were classified into two groups: a low
      serum PSA concentration group (n = 20) (<2.5 ng/mL) and a high-serum PSA
      concentration group with high risk of recurrence or metastasis (n = 11) (<=2.5
      ng/mL). There were significant differences in saliva PSA concentration between
      these groups (p < 0.05). Saliva PSA concentration correlated very well with serum
      PSA concentration in the high-serum PSA concentration group (gamma = 0.910, p <
      0.001) using Spearman's rank test, but no correlation in the low-serum PSA
      concentration group. This result suggests that saliva PSA is associated with
      blood PSA in patients with recurrent or metastatic PA and may, therefore, be a
      useful PA biomarker.

PMID- 21854253
TI  - Human muscle-derived cell populations isolated by differential adhesion rates:
      phenotype and contribution to skeletal muscle regeneration in Mdx/SCID mice.
AB  - Muscle-derived stem cells (MDSCs) isolated from murine skeletal tissue by the
      preplate method have displayed the capability to commit to the myogenic lineage
      and regenerate more efficiently than myoblasts in skeletal and cardiac muscle in
      murine Duchenne Muscular Dystrophy mice (mdx). However, until now, these studies
      have not been translated to human muscle cells. Here, we describe the isolation,
      by a preplate technique, of candidate human MDSCs, which exhibit myogenic and
      regenerative characteristics similar to their murine counterparts. Using the
      preplate isolation method, we compared cells that adhere faster to the flasks,
      preplate 2 (PP2), and cells that adhere slower, preplate 6 (PP6). The human PP6
      cells express several markers of mesenchymal stem cells and are distinct from
      human PP2 (a myoblast-like population) based on their expression of CD146 and
      myogenic markers desmin and CD56. After transplantation to the gastrocnemius
      muscle of mdx/SCID mice, we observe significantly higher levels of PP6 cells
      participating in muscle regeneration as compared with the transplantation of PP2
      cells. This study supports some previous findings related to mouse preplate
      cells, and also identifies some differences between mouse and human muscle
      preplate cells.

PMID- 21854255
TI  - Antigenotoxic ketosteroid from the red algae Jania adhaerens.
AB  - A new ketosteroid, 6beta,16beta-dihydroxycholest-4-en-3-one (1), in addition to
      the known 6beta-hydroxycholest-4-en-3-one (2), 6beta-hydroxycholest-4,22-dien-3
      one (3) and 16beta-hydroxy-5alpha-cholestan-3,6-dione (4), was isolated from the
      red alga Jania adhaerens. The structures were assigned on the basis of (1)H- and
      (13)C-NMR experiments. The new compound (1) was evaluated for its genotoxic and
      cytotoxic activities and found to possess protective antigenotoxicity in human
      peripheral blood cells.

PMID- 21854256
TI  - Assessment of safety data.

PMID- 21854257
TI  - How many, precisely?

PMID- 21854258
TI  - Effects of bone morphogenetic proteins on primary human renal cells and the
      generation of bone morphogenetic protein-7-expressing cells for application in
      bioartificial kidneys.
AB  - Bioartificial kidneys (BAKs) contain renal cells, and primary human renal
      proximal tubule cells (HPTCs) have been applied in clinical trials with BAKs.
      Cell performance within the device is critical. HPTC performance is often
      compromised under in vitro conditions because of dedifferentiation,
      transdifferentiation, and tubule formation on substrate surfaces. Herein we
      tested whether treatments with human recombinant bone morphogenetic protein (BMP)
      2 or BMP-7 would improve HPTC performance. We found that both growth factors
      improved HPTC performance, but more consistent results were obtained with BMP-7.
      The effects were strongly concentration dependent, and for BMP-7, 25 ng/mL was
      the optimal concentration, which improved HPTC performance under static and under
      bioreactor conditions. As an alternative to supplementation with the purified
      growth factor, we generated HPTCs secreting human recombinant BMP-7. BMP-7
      secreted by the cells was bioactive and improved the functional performance of
      HPTCs, in agreement with our other findings. Together, the results suggested that
      either supplementation with purified BMP-7 or BMP-7-producing cells could be used
      to improve cell performance in BAKs. BAKs with BMP-7-producing cells could also
      be used to deliver the growth factor to kidney patients. Our results suggested
      that the amount of BMP-7 produced by HPTCs would be sufficient for therapeutic
      applications.

PMID- 21854259
TI  - A single-center experience with prone retroperitoneoscopic versus open renal
      surgery in children: an age- and procedure-matched comparison.
AB  - PURPOSE: We determined how surgical outcomes differ among children undergoing
      prone retroperitoneoscopic (RP) and open total and partial nephrectomies for
      benign renal disease. PATIENTS AND METHODS: A retrospective analysis was
      performed, using medical records of children who were undergoing benign renal
      surgery at a single institution from 2001 to 2010. Patients were divided into
      open or RP cohorts, then subdivided into those who were undergoing total or
      partial nephrectomies. A further breakdown by age (<3 years and >=3 years) was
      performed. Bilateral nephrectomies were separately evaluated. Surgical outcomes
      were compared across groups. RESULTS: There were 308 (333 renal units) children
      who underwent RP (n=154) or open (n=154) total or partial nephrectomies, 25 of
      which were bilateral (20 RP, 5 open); 199 patients underwent total nephrectomies
      (RP n=118, open n=81), and 109 underwent partial nephrectomies (RP n=36, open
      n=73). After controlling for age and concomitant procedures, operative times were
      similar for the RP total and bilateral nephrectomy groups, but longer for the RP
      partial nephrectomy group, compared with their open counterparts. In both total
      and partial nephrectomies, the RP group had a shorter hospital stay. There were
      no open conversions in any of the RP groups and no differences in complications
      in the total, partial, and bilateral analyses. There were 13 patients who
      previously received peritoneal dialysis (8 bilateral RP, 3 unilateral RP, and 2
      unilateral open), all of whom resumed dialysis in a mean of 1.11 days.
      CONCLUSIONS: This is the largest series to date that compares RP and open renal
      surgeries in children. The RP and open approaches were comparably safe and
      efficacious. Hospital stays were significantly shorter in the RP total and
      partial groups, although operative times were significantly longer in the RP
      partial nephrectomy group. Prone retroperitoneoscopic surgery should be
      considered a viable option for renal surgery at any age.

PMID- 21854260
TI  - Evaluation of hemoglobin A1c criteria to assess preoperative diabetes risk in
      cardiac surgery patients.
AB  - OBJECTIVE: Hemoglobin A1c (A1C) has recently been recommended for diagnosing
      diabetes mellitus and diabetes risk (prediabetes). Its performance compared with
      fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well
      delineated. We compared the performance of A1C with that of FPG and 2HPG in
      preoperative cardiac surgery patients. METHODS: Data from 92 patients without a
      history of diabetes were analyzed. Patients were classified with diabetes or
      prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and
      specificity of the new A1C criteria were evaluated. RESULTS: All patients
      diagnosed with diabetes by A1C also had impaired fasting glucose, impaired
      glucose tolerance, or diabetes by other criteria. Using FPG as the reference,
      sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and
      using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity
      for identifying prediabetes with FPG as the reference were 51% and 51%,
      respectively, and with 2HPG were 53% and 51%, respectively. One-third each of
      patients with prediabetes was identified using FPG, A1C, or both. When testing
      A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to
      93% stipulating one or both tests are abnormal; specificity increased to 100% if
      both tests were required to be abnormal. CONCLUSIONS: In patients before cardiac
      surgery, A1C criteria identified the largest number of patients with diabetes and
      prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and
      characterized different groups of patients, therefore altering the distribution
      of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive
      and specific tool for identifying high-risk individuals with diabetes and
      prediabetes.

PMID- 21854261
TI  - Direct feeding of microencapsulated bacteriophages to reduce Salmonella
      colonization in pigs.
AB  - Salmonella shedding often increases in pigs after transportation and/or lairage.
      We previously showed that administering anti-Salmonella bacteriophages to pigs by
      gavage significantly reduced Salmonella colonization when the pigs were exposed
      to a Salmonella-contaminated holding pen. Here we tested whether a
      microencapsulated phage cocktail would remain effective if the treatment was
      administered to pigs in the feed. Pigs (n=21) were randomly placed into three
      groups: feed, gavage, and control. The feed group was direct-fed a
      microencapsulated phage cocktail daily for 5 days. On the fifth day, the gavage
      group received the same phage cocktail by gavage, whereas control pigs received a
      mock treatment containing no phage. All pigs were then orally challenged with
      Salmonella enterica serovar Typhimurium. Fecal swab samples were collected every
      2 h. At 6 h postchallenge, all pigs were euthanized, and ileal and cecal contents
      and mesenteric lymph nodes were collected and analyzed for the challenge
      organism. Pigs in the feed group were less likely to shed Salmonella Typhimurium
      at 2 h (38.1%) and 4 h (42.9%) postchallenge than pigs in both the gavage (2 h:
      71.4%; 4 h: 81.1%) and control (2 h: 71.4%; 4 h: 85.7%) groups (p<0.05).
      Likewise, concentrations of Salmonella Typhimurium in ileal (2.0 log(10) colony
      forming units [CFU]/mL [contents]) and cecal (2.7 log(10) CFU/mL) contents from
      feed pigs were lower than ileal (3.0 log(10) CFU/mL) and cecal (3.7 log(10)
      CFU/mL) contents from control pigs. High concentrations of anti-Salmonella phages
      were detected in ileal and cecal contents from both feed and gavage pigs (feed
      ileal: 1.4*10(6); feed cecal 8.5*10(6); gavage ileal 2.0*10(4); gavage cecal:
      2.2*10(3)). It is concluded that direct feeding of microencapsulated phages is a
      practical and effective means of reducing Salmonella colonization and shedding in
      pigs.

PMID- 21854262
TI  - A survey of beta-lactamase and 16S rRNA methylase genes among fluoroquinolone
      resistant Escherichia coli isolates and their horizontal transmission in
      Shandong, China.
AB  - The prevalence of beta-lactamase, 16S rRNA methylase genes, and plasmid-mediated
      fluoroquinolone-resistance (PMQR) determinants (qnrC and qnrD) was determined by
      polymerase chain reaction in fluoroquinolone-resistant Escherichia coli isolated
      from a chicken farm, a pig farm, and a hospital in Shandong, China in 2007. The
      bla(TEM) and bla(CTX-M) were the most prevalent beta-lactamase genes in isolates
      from chickens (88.4%, 175/198 and 81.3%, 161/198) and hospitalized patients
      (87.8%, 122/139 and 69.1%, 96/139). The bla(TEM) was the most prevalent beta
      lactamase gene observed in isolates from pigs (98.5%, 135/137). The gene bla(CMY
      2) was also predominant among isolates from chickens (20.2%, 40/198). The bla(LAP
      1) gene was first detected in one strain from chickens and humans (pig farm
      workers) in China. Only one strain from hospitalized patients was found to
      possess bla(SHV). The rmtB was the most prevalent 16S rRNA methylase gene
      detected in isolates from chickens (19.7%, 39/198) and hospitalized patients
      (15.8%, 22/139). To our knowledge, this is the first report of the detection of
      the qnrD gene in E. coli from chickens and pigs in China. The qnrC and bla(KPC)
      genes were not detected in any of the isolates. Results of southern hybridization
      revealed that PMQR determinants, beta-lactamases, and 16S rRNA methylase genes
      were located on the same plasmid in E. coli strains derived from patients. Also,
      PMQR determinants and beta-lactamase genes were localized on the same plasmid in
      an E. coli strain of animal origin. Results of conjugation experiments revealed
      that all of these plasmid-based resistance genes can be transferred by
      conjugation through horizontal transmission.

PMID- 21854263
TI  - Salmonella spp. and Shiga toxin-producing Escherichia coli prevalence in an
      ocellated lizard (Timon lepidus) research center in Spain.
AB  - The aim of this work was to study the epidemiological status of Salmonella spp.
      and Shiga toxin-producing Escherichia coli (STEC) in an ocellated lizard research
      center focusing on the risk and hygiene aspects. Fecal and environmental samples
      were collected and examined for Salmonella spp. and STEC. Isolates were detected
      using real-time polymerase chain reaction (RT-PCR) and characterized using
      serotyping and pulsed-field gel electrophoresis (PFGE). Overall, 52% of samples
      were positive for Salmonella spp. using RT-PCR and seven isolates were obtained
      from samples from ocellated lizards and their environment, whereas no samples
      were positive for STEC. Salmonella isolates belonged to S. enterica subsp.
      enterica serovar Kibusi and S. enterica subsp. salamae serovars 41:z10:z6 and
      18:z10:z6, some of which have previously been isolated from human sources.
      Indistinguishable and closely related PFGE types were found, which supported the
      existence of horizontal transmission between animals due to crowding of animals
      and the persistence of Salmonella in the environment. The results of the current
      study emphasize the need for improved prevention efforts and good hygiene
      practices in research centers, recuperation centers, and zoos with reptiles to
      minimize the exposure of personnel and visitors to this pathogen.

PMID- 21854264
TI  - Drinking water test methods in crisis-afflicted areas: comparison of methods
      under field conditions.
AB  - To simplify the testing of drinking water in crisis-afflicted areas (as in Kosovo
      in 2007), rapid test methods were compared with the standard test. For
      Escherichia coli and coliform pathogens, rapid tests were made available:
      Colilert((r))-18, P/A test with 4-methylumbelliferyl-beta-D-glucoronid, and m
      Endo Broth. Biochemical differentiation was carried out by EnterotubeTM II.
      Enterococci were determined following the standard ISO test and by means of
      EnterolertTM. Four hundred ninety-nine water samples were tested for E. coli and
      coliforms using four methods. Following the standard method, 20.8% (n=104) of the
      samples contained E. coli, whereas the rapid tests detected between 19.6% (m-Endo
      Broth, 92.0% concordance) and 20.0% (concordance: 93.6% Colilert-18 and 94.8% P/A
      test) positive samples. Regarding coliforms, the percentage of concordant results
      ranged from 98.4% (P/A-test) to 99.0% (Colilert-18). Colilert-18 and m-Endo Broth
      detected even more positive samples than the standard method did. Enterococci
      were detected in 93 of 573 samples by the standard method, but in 92 samples by
      Enterolert (concordance: 99.5%). Considering the high-quality equipment and time
      requirements of the standard method, the use of rapid tests in crisis-afflicted
      areas is sufficiently reliable.

PMID- 21854265
TI  - A Campylobacter jejuni Dps homolog has a role in intracellular survival and in
      the development of campylobacterosis in neonate piglets.
AB  - Iron acquisition is an absolute requirement by most microorganisms for host
      survival. In this work, we investigated the Campylobacter jejuni iron binding Dps
      protein for a potential role in virulence. In vitro assays using J774A.1
      macrophage-like cells demonstrated a 2.5 log reduction in C. jejuni survival of
      the Dps mutant and a reduction of four logs in invasion of HEp-2 epithelial cells
      compared to the wild-type strain. To examine the role of the dps gene in host
      pathogenesis, the piglet model was used in C. jejuni challenge studies. In vivo
      inoculation studies of newborn piglets with wild-type C. jejuni demonstrated an
      11-fold upregulation of the dps gene and intestinal lesion production typical of
      campylobacteriosis in humans. In contrast, piglets inoculated with the dps mutant
      were not colonized and remained normal throughout the study period. Mucosal
      lesion production was restored in piglets inoculated with the complemented Dps
      mutant strain. Based on these results, we conclude that the C. jejuni Dps homolog
      is a virulence factor in the production of campylobacteriosis, and warrants
      further investigation.

PMID- 21854266
TI  - Destructive and nondestructive procedures to obtain chicken carcass samples for
      Escherichia coli and Salmonella spp. detection.
AB  - Destructive and nondestructive sampling procedures were compared for Escherichia
      coli and Salmonella spp. detection in 60 fresh chicken carcasses, which were
      submitted to the following sampling procedures: rinsing, skin swabbing, tissue
      excision, and skin excision; the proximity or not to the cloacae region was also
      considered. The obtained results were compared to identify significant
      differences (p<0.05). Forty eight chicken carcasses were positive for E. coli,
      and five were positive for Salmonella spp. For E. coli, nonsignificant
      differences were observed between rinsing and tissue excision, rinsing and skin
      excision, and skin excision and tissue excision (p>0.05), thus indicating
      equivalencies between these techniques. Skin swabbing produced a statistically
      significant lower frequency of positive results (p<0.05) than all other
      techniques for E. coli, thus indicating its inadequacy for detection of this
      microorganism. For Salmonella spp., no significant differences were observed
      between the sampling techniques (p>0.05), possibly due to the low overall
      frequency of positive carcasses. No significant differences in the number of
      positive samples (E. coli or Salmonella spp.) were observed between samples
      collected near or far from the cloacae region (p>0.05), regardless of the
      sampling technique. The obtained results demonstrate that the tested sampling
      techniques were equivalent for Salmonella spp. detection in chicken carcasses, as
      observed for E. coli with the exception of skin swabbing.

PMID- 21854267
TI  - The design and analysis of multisite effectiveness trials: a decade of progress
      in the National Drug Abuse Clinical Trials Network.

PMID- 21854269
TI  - Ten take home lessons from the first 10 years of the CTN and 10 recommendations
      for the future.
AB  - BACKGROUND: The first 10 years of the National Institute on Drug Abuse's Clinical
      Trials Network (CTN) yielded a wealth of data on the effectiveness of a number of
      behavioral, pharmacological, and combined approaches in community-based settings.
      METHODS: We summarize some of the methodological contributions and lessons
      learned from the behavioral trials conducted during its first ten years,
      including the capacity and enormous potential of this national research
      infrastructure. RESULTS: The CTN made contributions to the methodology of
      effectiveness research; new insights from secondary analyses; the extent to which
      approaches with strong evidence bases, such as contingency management, extend
      their effectiveness to real world clinical settings; new data on 'standard
      treatment' as actually practiced in community programs, the extent to which
      retention remains a major issue in the field; important data on the safety of
      specific behavioral therapies for addiction; and heightened the importance of
      continued sustained attention to bridging the gap between treatment and research.
      CONCLUSIONS: Areas of focus for the CTN's future include defining common outcome
      measures to be used in treatment outcome studies for illicit drugs; incorporating
      performance indicators and measures of clinical significance; conducting
      comparative outcome studies; contributing to the understanding of effective
      treatments of comorbidity; reaching underserved populations; building
      implementation science; understanding long-term outcomes of current treatments
      and sustaining treatment effects; and conducting future trials more efficiently.

PMID- 21854270
TI  - NIDA's Clinical Trials Network: an opportunity for HIV research in community
      substance abuse treatment programs.
AB  - BACKGROUND/OBJECTIVES: HIV continues to be a significant problem among substance
      users and their sexual partners in the United States. The National Drug Abuse
      Treatment Clinical Trials Network (CTN) offers a national platform for
      effectiveness trials of HIV interventions in community substance abuse treatment
      programs. This article presents the HIV activities of the CTN during its first 10
      years. RESULTS: While emphasizing CTN HIV protocols, this article reviews the (1)
      HIV context for this work; (2) the collaborative process among providers,
      researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV
      work was based; (3) results of CTN HIV protocols and HIV secondary analyses in
      CTN non-HIV protocols; and (4) implications for future HIV intervention
      effectiveness research in community substance abuse treatment programs.
      CONCLUSION/SIGNIFICANCE: While the feasibility of engaging frontline providers in
      this research is highlighted, the limitations of small to medium effect sizes and
      weak adoption and sustainability in everyday practice are also discussed.

PMID- 21854271
TI  - Is monogamy or committed relationship status a marker for low sexual risk among
      men in substance abuse treatment? Clinical and methodological considerations.
AB  - BACKGROUND: HIV prevention interventions often promote monogamy to reduce sexual
      risk. However, there is little consensus about how to define monogamy. OBJECTIVE:
      To determine the extent to which recent monogamy and/or being in a committed
      relationship serve as markers for low sexual risk among men in substance abuse
      treatment. METHODS: Participants were 360 men enrolled in the National Institute
      on Drug Abuse Clinical Trials Network "Real Men Are Safe" protocol who completed
      all assessments (baseline, 3 months, and 6 months). Self-reported behaviors
      included number of sexual partners, type of relationships, frequency of
      vaginal/anal intercourse, and percentage of condom use. RESULTS: The rate of self
      reported monogamy in the prior 90 days was stable across assessments (54.2%,
      53.1%, 58.3%). However, at each assessment 7.5-10% of monogamous men identified
      their partner as a casual partner, and only 123 (34.2%) reported being monogamous
      at every assessment. Of these, 20 (5.6%) reported being monogamous with different
      partners across assessments. Men with both committed relationship and casual
      partners reported more condom use with their committed relationship partners than
      men with only a committed relationship partner. CONCLUSION: Clinicians and
      researchers should consider individual relationship context and behavior and
      avoid assuming that recent monogamy or being in a committed relationship denotes
      low risk. SCIENTIFIC SIGNIFICANCE: This study provides evidence that, in male
      drug users, monogamy does not necessarily reflect low sexual risk. Rather,
      "monogamous" men actually encompass various combinations of partner types and
      levels of risk behavior that are unstable, even over brief time periods.
      Clinicians and researchers must take these variations into account.

PMID- 21854272
TI  - Gender research in the National Institute on Drug Abuse National Treatment
      Clinical Trials Network: a summary of findings.
AB  - BACKGROUND: The National Institute of Drug Abuse's National Drug Abuse Treatment
      Clinical Trials Network (CTN) was established to foster translation of research
      into practice in substance abuse treatment settings. The CTN provides a unique
      opportunity to examine in multi-site, translational clinical trials, the outcomes
      of treatment interventions targeting vulnerable subgroups of women; the
      comparative effectiveness of gender-specific protocols to reduce risk behaviors;
      and gender differences in clinical outcomes. OBJECTIVES: To review gender-related
      findings from published CTN clinical trials and related studies from January 2000
      to March 2010. METHODS: CTN studies were selected for review if they focused on
      treatment outcomes or services for special populations of women with substance
      use disorders (SUDs) including those with trauma histories, pregnancy, co
      occurring eating and other psychiatric disorders, and HIV risk behaviors; or
      implemented gender-specific protocols. The CTN has randomized 11,500 participants
      (41% women) across 200 clinics in 24 randomized controlled trials in community
      settings, of which 4 have been gender-specific. RESULTS: This article summarizes
      gender-related findings from CTN clinical trials and related studies, focusing on
      trauma histories, pregnancy, co-occurring eating and other psychiatric disorders,
      and HIV risk behaviors. CONCLUSIONS: These published studies have expanded the
      evidence base regarding interventions for vulnerable groups of women with SUDs as
      well as gender-specific interventions to reduce HIV risk behaviors in substance
      using men and women. The results also underscore the complexity of accounting for
      gender in the design of clinical trials and analysis of results. SCIENTIFIC
      SIGNIFICANCE: To fully understand the relevance of gender-specific moderators and
      mediators of outcome, it is essential that future translational studies adopt
      more sophisticated approaches to understanding and measuring gender-relevant
      factors and plan sample sizes that are adequate to support more nuanced analytic
      methods.

PMID- 21854273
TI  - Comparative profiles of men and women with opioid dependence: results from a
      national multisite effectiveness trial.
AB  - BACKGROUND: Accumulating evidence indicates important gender differences in
      substance use disorders. Little is known, however, about gender differences and
      opioid use disorders. OBJECTIVES: To compare demographic characteristics,
      substance use severity, and other associated areas of functioning (as measured by
      the Addiction Severity Index-Lite (ASI-Lite)) among opioid-dependent men and
      women participating in a multisite effectiveness trial. METHODS: Participants
      were 892 adults screened for the National Institute on Drug Abuse Clinical Trials
      Network investigation of the effectiveness of two buprenorphine tapering
      schedules. RESULTS: The majority of men and women tested positive for oxycodone
      (68% and 65%, respectively) and morphine (89% each). More women than men tested
      positive for amphetamines (4% vs. 1%, p < .01), methamphetamine (11% vs. 4%, p <
      .01), and phencyclidine (8% vs. 4%, p = .02). More men than women tested positive
      for methadone (11% vs. 6%, p = .05) and marijuana (22% vs. 15%, p = .03). Craving
      for opioids was significantly higher among women (p < .01). Men evidenced higher
      alcohol (p < .01) and legal (p = .04) ASI composite scores, whereas women had
      higher drug (p < .01), employment (p < .01), family (p < .01), medical (p < .01),
      and psychiatric (p < .01) ASI composite scores. Women endorsed significantly more
      current and past medical problems. CONCLUSIONS: Important gender differences in
      the clinical profiles of opioid-dependent individuals were observed with regard
      to substance use severity, craving, medical conditions, and impairment in
      associated areas of functioning. The findings enhance understanding of the
      characteristics of treatment-seeking men and women with opioid dependence, and
      may be useful in improving identification, prevention, and treatment efforts for
      this challenging and growing population.

PMID- 21854274
TI  - Conducting research with racial/ethnic minorities: methodological lessons from
      the NIDA Clinical Trials Network.
AB  - BACKGROUND: Multiple studies in the National Institute on Drug Abuse Clinical
      Trials Network (CTN) demonstrate strategies for conducting effective substance
      abuse treatment research with racial/ethnic minorities (REMs). OBJECTIVES: The
      objectives of this article are to describe lessons learned within the CTN to (1)
      enhance recruitment, retention, and other outcomes; (2) assess measurement
      equivalence; and (3) use data analytic plans that yield more information. METHOD:
      This article includes background information and examples from multiple CTN
      studies on inclusion, measurement, and data analysis. RESULTS AND CONCLUSIONS:
      Seven recommendations are included for conducting more effective research on
      REMs.

PMID- 21854275
TI  - Research partnerships between academic institutions and American Indian and
      Alaska Native Tribes and organizations: effective strategies and lessons learned
      in a multisite CTN study.
AB  - BACKGROUND: Community Based and Tribally Based Participatory Research (CBPR/TPR)
      are approaches that can be successful for developing ethical and effective
      research partnerships between academic institutions and Tribes and Native
      organizations. OBJECTIVES: The NIDA Clinical Trials Network funded a multi-site,
      exploratory study using CBPR/TPR to begin to better understand substance abuse
      issues of concern to some Tribes and Native organizations as well as strengths
      and resources that exist in these communities to address these concerns.
      Attention was paid to the development and maintenance of research partnerships in
      each of the sites. METHODS: Each of the five partnerships is briefly described
      and common as well as unique challenges and successes are identified. RESULTS: A
      summary of the common themes for developing these collaborative research efforts
      is provided. CONCLUSION: True, collaborative research partnerships require a
      great deal of time and effort in order to develop mutual trust, understanding,
      knowledge, and collaboration that will guide research that is rigorous as well as
      ethical, effective, and culturally appropriate. SCIENTIFIC SIGNIFICANCE: As AIAN
      communities become increasingly sophisticated partners in, and consumers of,
      research, CBPR and TPR are emerging as effective, ethical, culturally
      appropriate, and acceptable approaches. This can serve to improve the science we
      engage in with AIAN communities, add to the scarce literature regarding AIAN
      communities, and better serve AIAN communities in addressing health disparities
      and improving health.

PMID- 21854276
TI  - Determining the primary endpoint for a stimulant abuse trial: lessons learned
      from STRIDE (CTN 0037).
AB  - BACKGROUND: No consensus is available for identifying the best primary outcome
      for substance use disorder trials, making interpretation across trials difficult.
      Abstinence is the most desirable treatment outcome although a wide variety of
      other endpoints have been used. OBJECTIVES: This report provides a framework for
      determining an optimal primary endpoint and the relevant measurement approach for
      substance use disorder treatment trials. The framework was developed based on a
      trial for stimulant abuse using exercise as an augmentation treatment, delivered
      within the NIDA Clinical Trials Network. The use of a common endpoint across
      trials will facilitate comparisons of treatment efficacy. METHODS: Primary
      endpoint options in existing substance abuse studies were evaluated. This
      evaluation included surveys of the literature for endpoints and measurement
      approaches, followed by assessment of endpoint choices against study design
      issues, population characteristics, tests of sensitivity, and tests of clinical
      meaningfulness. CONCLUSION: We concluded that the best current choice for a
      primary endpoint is percent days abstinent, as measured by the Time Line Follow
      Back interview conducted three times a week with recall aided by a take-home
      Substance Use Diary. To improve the accuracy of the self-reported drug use, the
      results of qualitative urine drug screens will be used in conjunction with the
      Time Line Follow Back results. SCIENTIFIC SIGNIFICANCE: There is a need for a
      standardized endpoint in this field to allow for comparison across treatment
      studies, and we suggest that the recommended candidate endpoint be considered.
      However, the study design and goals ultimately must guide the final decision.

PMID- 21854277
TI  - Power of automated algorithms for combining time-line follow-back and urine drug
      screening test results in stimulant-abuse clinical trials.
AB  - BACKGROUND: In clinical trials of treatment for stimulant abuse, researchers
      commonly record both Time-Line Follow-Back (TLFB) self-reports and urine drug
      screen (UDS) results. OBJECTIVES: To compare the power of self-report,
      qualitative (use vs. no use) UDS assessment, and various algorithms to generate
      self-report-UDS composite measures to detect treatment differences via t-test in
      simulated clinical trial data. METHODS: We performed Monte Carlo simulations
      patterned in part on real data to model self-report reliability, UDS errors,
      dropout, informatively missing UDS reports, incomplete adherence to a urine
      donation schedule, temporal correlation of drug use, number of days in the study
      period, number of patients per arm, and distribution of drug-use probabilities.
      Investigated algorithms include maximum likelihood and Bayesian estimates, self
      report alone, UDS alone, and several simple modifications of self-report
      (referred to here as ELCON algorithms) which eliminate perceived contradictions
      between it and UDS. RESULTS: Among the algorithms investigated, simple ELCON
      algorithms gave rise to the most powerful t-tests to detect mean group
      differences in stimulant drug use. CONCLUSIONS: Further investigation is needed
      to determine if simple, naive procedures such as the ELCON algorithms are optimal
      for comparing clinical study treatment arms. But researchers who currently
      require an automated algorithm in scenarios similar to those simulated for
      combining TLFB and UDS to test group differences in stimulant use should consider
      one of the ELCON algorithms. SCIENTIFIC SIGNIFICANCE: This analysis continues a
      line of inquiry which could determine how best to measure outpatient stimulant
      use in clinical trials (NIDA. NIDA Monograph-57: Self-Report Methods of
      Estimating Drug Abuse: Meeting Current Challenges to Validity. NTIS PB 88248083.
      Bethesda, MD: National Institutes of Health, 1985; NIDA. NIDA Research Monograph
      73: Urine Testing for Drugs of Abuse. NTIS PB 89151971. Bethesda, MD: National
      Institutes of Health, 1987; NIDA. NIDA Research Monograph 167: The Validity of
      Self-Reported Drug Use: Improving the Accuracy of Survey Estimates. NTIS PB
      97175889. GPO 017-024-01607-1. Bethesda, MD: National Institutes of Health,
      1997).

PMID- 21854278
TI  - Assessing drug use during follow-up: direct comparison of candidate outcome
      definitions in pooled analyses of addiction treatment studies.
AB  - BACKGROUND: Selection of appropriate outcome measures is important for clinical
      studies of drug addiction treatment. Researchers use various methods for
      collecting drug use outcomes and must consider substances to be included in a
      urine drug screen (UDS); accuracy of self-report; use of various instruments and
      procedures for collecting self-reported drug use; and timing of outcome
      assessments. OBJECTIVES: We sought to define a set of candidate measures to (1)
      assess their intercorrelation and (2) identify any differences in results.
      METHODS: Data were combined from completed protocols in the National Institute on
      Drug Abuse Clinical Trials Network (CTN), with a total of 1897 participants. We
      defined nine outcome measures based on UDS, self-report, or a combination.
      Multivariable, multilevel generalized estimating equation models were used to
      assess subgroup differences in intervention success, controlling for baseline
      differences and accounting for clustering by CTN protocols. RESULTS: There were
      high correlations among all candidate outcomes. All outcomes showed consistent
      overall results with no significant intervention impact on drug use during follow
      up. However, with most UDS variables, but not with self-report or "corrected self
      report," we observed a significant gender-ethnicity interaction with benefit
      shown in African American women, White women, and Hispanic men. CONCLUSION:
      Despite strong associations between candidate measures, we found some important
      differences in results. SCIENTIFIC SIGNIFICANCE: In this study, we demonstrated
      the potential utility and impact of combining UDS and self-report data for drug
      use assessment. Our results suggest possible differences in intervention efficacy
      by gender and ethnicity, but highlight the need to cautiously interpret observed
      interactions.

PMID- 21854279
TI  - Zero-inflated and hurdle models of count data with extra zeros: examples from an
      HIV-risk reduction intervention trial.
AB  - BACKGROUND: In clinical trials of behavioral health interventions, outcome
      variables often take the form of counts, such as days using substances or
      episodes of unprotected sex. Classically, count data follow a Poisson
      distribution; however, in practice such data often display greater heterogeneity
      in the form of excess zeros (zero-inflation) or greater spread in the values
      (overdispersion) or both. Greater sample heterogeneity may be especially common
      in community-based effectiveness trials, where broad eligibility criteria are
      implemented to achieve a generalizable sample. OBJECTIVES: This article reviews
      the characteristics of Poisson model and the related models that have been
      developed to handle overdispersion (negative binomial (NB) model) or zero
      inflation (zero-inflated Poisson (ZIP) and Poisson hurdle (PH) models) or both
      (zero-inflated negative binomial (ZINB) and negative binomial hurdle (NBH)
      models). METHODS: All six models were used to model the effect of an HIV-risk
      reduction intervention on the count of unprotected sexual occasions (USOs), using
      data from a previously completed clinical trial among female patients (N = 515)
      participating in community-based substance abuse treatment (Tross et al.
      Effectiveness of HIV/AIDS sexual risk reduction groups for women in substance
      abuse treatment programs: Results of NIDA Clinical Trials Network Trial. J Acquir
      Immune Defic Syndr 2008; 48(5):581-589). Goodness of fit and the estimates of
      treatment effect derived from each model were compared. RESULTS: The ZINB model
      provided the best fit, yielding a medium-sized effect of intervention.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This article illustrates the
      consequences of applying models with different distribution assumptions on the
      data. If a model used does not closely fit the shape of the data distribution,
      the estimate of the effect of the intervention may be biased, either over- or
      underestimating the intervention effect.

PMID- 21854280
TI  - Some considerations for excess zeroes in substance abuse research.
AB  - BACKGROUND: Count data collected in substance abuse research often come with an
      excess of "zeroes," which are typically handled using zero-inflated regression
      models. However, there is a need to consider the design aspects of those studies
      before using such a statistical model to ascertain the sources of zeroes.
      OBJECTIVES: We sought to illustrate hurdle models as alternatives to zero
      inflated models to validate a two-stage decision-making process in situations of
      "excess zeroes." METHODS: We use data from a study of 45 cocaine-dependent
      subjects where the primary scientific question was to evaluate whether study
      participation influences drug-seeking behavior. The outcome, "the frequency
      (count) of cocaine use days per week," is bounded (ranging from 0 to 7). We fit
      and compare binomial, Poisson, negative binomial, and the hurdle version of these
      models to study the effect of gender, age, time, and study participation on
      cocaine use. RESULTS: The hurdle binomial model provides the best fit. Gender and
      time are not predictive of use. Higher odds of use versus no use are associated
      with age; however once use is experienced, odds of further use decrease with
      increase in age. Participation was associated with higher odds of no-cocaine use;
      once there is use, participation reduced the odds of further use. CONCLUSION: Age
      and study participation are significantly predictive of cocaine-use behavior.
      SCIENTIFIC SIGNIFICANCE: The two-stage decision process as modeled by a hurdle
      binomial model (appropriate for bounded count data with excess zeroes) provides
      interesting insights into the study of covariate effects on count responses of
      substance use, when all enrolled subjects are believed to be "at-risk" of use.

PMID- 21854281
TI  - Modeling site effects in the design and analysis of multi-site trials.
AB  - BACKGROUND: Careful consideration of site effects is important in the analysis of
      multi-site clinical trials for drug abuse treatment. The statistical choices for
      modeling these effects have implications for both trial planning and
      interpretation of findings. OBJECTIVES: Three broad approaches for modeling site
      effects are presented: omitting site from the analysis; modeling site as a fixed
      effect; and modeling site as a random effect. Both the direct effect of site and
      the interaction of site and treatment are considered. METHODS: The statistical
      model, and consequences, for each approach are presented along with examples from
      existing clinical trials. Power analysis calculations provide sample size
      requirements for adequate statistical power for studies utilizing 6, 8, 10, 12,
      14, and 16 treatment sites. RESULTS: Results of the power analyses showed that
      the total sample required falls rapidly as the number of sites increases in the
      random effect approach. In the fixed effect approach in which the interaction of
      site and treatment is considered, the required number of participants per site
      decreases as the number of sites increases. CONCLUSIONS: Ignoring site effects is
      not a viable option in multi-site clinical trials. There are advantages and
      disadvantages to the fixed effect and random effect approaches to modeling site
      effects. SCIENTIFIC SIGNIFICANCE: The distinction between efficacy trials and
      effectiveness trials is rarely sharp. The choice between random effect and fixed
      effect statistical modeling can provide different benefits depending on the goals
      of the study.

PMID- 21854282
TI  - An exploration of site effects in a multisite trial of OROS-methylphenidate for
      smokers with attention deficit/hyperactivity disorder.
AB  - BACKGROUND: Multisite trials, the gold standard for conducting studies in
      community-based settings, can mask variability across sites resulting in
      misrepresentation of effects in specific sites. In a placebo-controlled trial of
      osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment
      for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD),
      three types of sites were selected according to their clinical research specialty
      (ADHD, smoking cessation, and general mental health). OBJECTIVE: Analysis was
      conducted to determine if clinical outcomes, that is, reduction in ADHD symptoms
      and smoking cessation rates, and the effect of treatment on these outcomes would
      differ by type of site. METHOD: A total of 255 adult smokers diagnosed with ADHD
      were enrolled in three clinic types: 72 in ADHD, 79 in tobacco dependence, and
      104 in the mental health clinics. RESULTS: The three site-types were similar in
      demographic characteristics, smoking history, baseline level of ADHD symptoms,
      and history of psychiatric illness. Site-type but not a site-type by treatment
      interaction predicted prolonged smoking abstinence. A significant three-way
      interaction of site-type, treatment, and time-predicted improvement in ADHD
      symptoms. Moderate to strong effects of OROS-MPH relative to placebo were
      observed in the mental health and the ADHD clinics; a weak effect was observed in
      the tobacco dependence clinics. CONCLUSION: OROS-MPH benefit varied by site for
      reducing ADHD symptoms but not for improving smoking abstinence. SCIENTIFIC
      SIGNIFICANCE: Assessment of site-type effects can indicate the generalizability
      of findings from multisite trials and should be routinely incorporated in the
      design of multisite trials.

PMID- 21854283
TI  - Site selection in community-based clinical trials for substance use disorders:
      strategies for effective site selection.
AB  - BACKGROUND: The importance of conducting substance use disorder treatment
      research in real-world settings is now well recognized. While this approach to
      clinical trials research offers a variety of benefits, challenges also arise.
      Selecting high-quality sites to participate is critical to recruitment,
      retention, and overall trial performance when conducting multi-site, community
      based clinical trials of treatments for substance use disorders. OBJECTIVES: Over
      the past 10 years, the National Institute on Drug Abuse-sponsored National Drug
      Abuse Treatment Clinical Trials Network (CTN) has strived to conduct high
      quality, well-managed clinical trials. This includes developing methods for site
      selection to be used by investigators conducting CTN trials. METHODS: We review
      site selection strategies from two community-based multi-site clinical trials
      conducted under the auspices of the National Drug Abuse Treatment Clinical Trials
      Network. RESULTS: Issues relevant to site selection include the clinical trial
      design, availability of appropriate clinical population, and organizational
      attributes of potential clinical research sites. Site selection strategies
      include reviewing regional epidemiologic data, collecting standard site selection
      surveys, evaluating clinic data on existing patient populations, and site
      selection interviews and visits. CONCLUSION: This article describes
      considerations for selecting research sites and identifies specific strategies to
      employ when selecting community-based sites for participation in clinical trials.

PMID- 21854284
TI  - How practice and science are balanced and blended in the NIDA Clinical Trials
      Network: the bidirectional process in the development of the STAGE-12 protocol as
      an example.
AB  - BACKGROUND: Bidirectional, collaborative partnerships between academic
      researchers and practitioners have been a fundamental vehicle to achieve the
      National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) goal of
      improving outcomes of community-based drug treatment. These partnerships blend
      clinical perspectives of practitioners and methodological expertise of
      researchers working together to address clinically meaningful issues through
      randomized clinical trials conducted in community treatment settings. OBJECTIVES:
      Bidirectionality is a guiding principle of the CTN, but its operationlization at
      the practical level in protocol development and implementation has not been
      articulated. This descriptive article presents the development of one protocol as
      an example and model of this bidirectional, collaborative, iterative partnership
      between researchers and practitioners. METHODS: This article illuminates several
      specific issues encountered while developing STAGE-12, a behavioral intervention
      to facilitate 12-step mutual support group involvement, as well as the rationale
      for decisions taken to resolve each. RESULTS: The STAGE-12 protocol was
      successfully developed through a series of decisions taking into account both
      design factors and clinical practice needs and realities, thus maintaining a
      balance between methodological rigor and generalizability. CONCLUSION: The review
      demonstrates the process by which research and practice have been blended in
      protocol development, exemplifying the underlying principle of bidirectionality,
      a key element in the success of the NIDA CTN. SCIENTIFIC SIGNIFICANCE:
      Bidirectional partnerships as derived in the CTN, employing a hybrid model of
      efficacy-effectiveness research, are capable of designing and implementing
      protocols that are both methodologically rigorous and clinically meaningful, thus
      increasing likelihood of adoption and eventual improvement in public health.

PMID- 21854285
TI  - Design of NIDA CTN Protocol 0047: screening, motivational assessment, referral,
      and treatment in emergency departments (SMART-ED).
AB  - BACKGROUND: Medical settings such as emergency departments (EDs) present an
      opportunity to identify and provide services for individuals with substance use
      problems who might otherwise never receive any form of assessment, referral, or
      intervention. Although screening, brief intervention, and referral to treatment
      models have been extensively studied and are considered effective for individuals
      with alcohol problems presenting in EDs and other medical settings, the efficacy
      of such interventions has not been established for drug users presenting in EDs.
      OBJECTIVES: This article describes the design of a NIDA Clinical Trials Network
      protocol testing the efficacy of an screening, brief intervention, and referral
      to treatment model in medical EDs, highlighting considerations that are pertinent
      to the design of other studies targeting substance use behaviors in medical
      treatment settings. METHODS: The protocol is described, and critical design
      decisions are discussed. RESULTS: Design challenges included defining treatment
      conditions, study population, and site characteristics; developing the screening
      process; choosing the primary outcome; balancing brevity and comprehensiveness of
      assessment; and selecting the strategy for statistical analysis. CONCLUSION: Many
      of the issues arising in the design of this study will be relevant to future
      studies of interventions for addictions in medical settings. SCIENTIFIC
      SIGNIFICANCE: Optimal trial design is critical to determining how best to
      integrate substance abuse interventions into medical care.

PMID- 21854286
TI  - Relation of study design to recruitment and retention in CTN trials.
AB  - BACKGROUND: Recruitment and retention in randomized clinical trials are difficult
      in general and particularly so in trials of substance abuse treatments.
      Understanding trial design characteristics that could affect recruitment and
      retention rates would help in the design of future trials. OBJECTIVE: To test
      whether any of the following factors are associated with recruitment or
      retention: type of intervention, type of therapy, duration of treatment, total
      duration of trial, number of treatment sessions, number of follow-up visits,
      number of primary assessments, timing of primary assessments, number of case
      report form (CRF) pages at baseline, and number of CRF pages for the entire
      trial. METHODS: Recruitment and retention data from 24 Clinical Trials Network
      (CTN) trials conducted and completed between 2001 and 2010 were analyzed using
      single-factor analysis of variance and single-predictor regression methods to
      test their association with trial design characteristics. RESULTS: Almost all of
      the analyses performed did not show statistically significant patterns between
      recruitment and retention rates and the trial design characteristics considered.
      CONCLUSION: In CTN trials, the relationship between assessment burden on
      participants and length of trial, on the one hand, and recruitment and retention,
      on the other, is not as strong and direct as expected. Other factors must impinge
      on the conduct of the trial to influence trial participation. SCIENTIFIC
      SIGNIFICANCE: Researchers may deem slightly more justifiable to permit inclusion
      of some of the design features that previously were assumed to have a strong,
      negative influence on recruitment and retention, and should consider other
      strategies that may have a stronger, more direct effect on trial participation.

PMID- 21854287
TI  - Standardized patient walkthroughs in the National Drug Abuse Treatment Clinical
      Trials Network: common challenges to protocol implementation.
AB  - BACKGROUND: Training research staff to implement clinical trials occurring in
      community-based addiction treatment programs presents unique challenges.
      Standardized patient walkthroughs of study procedures may enhance training and
      protocol implementation. OBJECTIVES: Examine and discuss cross-site and cross
      study challenges of participant screening and data collection procedures
      identified during standardized patient walkthroughs of multi-site clinical
      trials. METHOD: Actors portrayed clients and "walked through" study procedures
      with protocol research staff. The study completed 57 walkthroughs during
      implementation of 4 clinical trials. RESULTS: Observers and walkthrough
      participants identified three areas of concern (consent procedures, screening and
      assessment processes, and protocol implementation) and made suggestions for
      resolving the concerns. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Standardized
      patient walkthroughs capture issues with study procedures previously unidentified
      with didactic training or unscripted rehearsals. Clinical trials within the
      National Drug Abuse Treatment Clinical Trials Network are conducted in addiction
      treatment centers that vary on multiple dimensions. Based on walkthrough
      observations, the national protocol team and local site leadership modify
      standardized operating procedures and resolve cross-site problems prior to
      recruiting study participants. The standardized patient walkthrough improves
      consistency across study sites and reduces potential site variation in study
      outcomes.

PMID- 21854288
TI  - Strategies for safety reporting in substance abuse trials.
AB  - BACKGROUND: Reporting all adverse events (AEs) and serious adverse events (SAEs)
      in substance use disorder (SUD) clinical trials has yielded limited relevant
      safety information and has been burdensome to research sites. OBJECTIVE: This
      article describes a new strategy utilizing standard data elements for AE and SAEs
      that defines a threshold to reduce unnecessary safety reporting burden in SUD
      clinical trials and describes retrospective review and prospective preliminary
      data on the strategy's safety reporting impact. METHODS: We developed a new
      strategy to standardize safety reporting and tailor reporting to the trial
      intervention risk. Protocols and safety data from 17 SUD clinical trials were
      reviewed. Retrospective analysis of five of these studies and prospective
      application to new studies is described. RESULTS: Across the 17 previously
      completed trials, a total of 11,220 AEs and 1330 SAEs were reported in the 6737
      participants. Wide variability in AE and SAE reporting rates were noted based on
      trial type and inconsistent reporting strategies. Application of the new,
      tailored safety strategy retrospectively and prospectively reduces reporting
      burden of irrelevant safety events. CONCLUSION: Comparison of the previous
      reporting strategies used in SUD trials to the new strategy demonstrates a more
      consistent safety system with a reduction in safety reporting burden while
      maintaining appropriate safety monitoring. SCIENTIFIC SIGNIFICANCE: Safety
      assessments should be tailored to the participant risks based on the trial
      intervention. The current strategies could be applied to safety assessments
      across all clinical trials in SUDs.

PMID- 21854289
TI  - Baseline matters: the importance of covariation for baseline severity in the
      analysis of clinical trials.
AB  - BACKGROUND: Clinical trials testing the effectiveness of interventions for
      addictions, HIV transmission risk, and other behavioral health problems are
      important to advancing evidence-based treatment. Such trials are expensive and
      time-consuming to conduct, but the underlying effect sizes tend to be modest, and
      often findings are disappointing, failing to show evidence of treatment effects.
      OBJECTIVES: To demonstrate how appropriate covariation for baseline severity can
      enhance detection of treatment effects. METHODS: Explication and case example.
      RESULTS: Baseline severity (the score of the outcome measure at baseline, prior
      to randomization) is often strongly associated with outcome in such studies.
      Covariation for baseline score may enhance detection of treatment effects,
      because the variance explained by the baseline score is removed from the error
      variance in the estimate of the difference in outcome between treatments.
      Alternatively, the effect of treatment may manifest in the form of a baseline-by
      treatment interaction. Common interaction patterns include that treatment may be
      more effective among patients with higher levels of baseline severity, or
      treatment may be more effective among patients with low severity at baseline
      ('relapse prevention' effect). Such effects may be important to developing
      treatment guidelines and offer clues toward understanding the mechanisms of
      action of treatments and of the disorders. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: This article illustrates principles of covariation for baseline and
      the baseline-by-treatment interaction in nontechnical graphical terms, and
      discusses examples from clinical trials. Implications for the design and analysis
      of clinical trials are discussed, and it is argued that covariation for baseline
      severity of the outcome measure and testing of the baseline-by-treatment
      interaction should be considered for inclusion in the primary outcome analyses of
      treatment effectiveness trials of substantial size.

PMID- 21854290
TI  - Participant characteristics and buprenorphine dose.
AB  - BACKGROUND: Clinical parameters for determining buprenorphine dose have not been
      adequately examined in treatment outcome research. OBJECTIVES: This study is a
      secondary analysis of data collected in a recently completed comparison of
      buprenorphine taper schedules conducted as part of the National Institute on Drug
      Abuse's Clinical Trials Network to assess whether participant baseline
      characteristics are associated with buprenorphine dose. METHODS: After 3 weeks of
      flexible dosing, 516 participants were categorized by dose provided in the final
      dosing week (9.3% received a final week dose of 8 mg buprenorphine, 27.3%
      received 16 mg, and 63.4% received 24 mg). RESULTS: Findings show that final week
      dose groups differed in baseline demographic and drug use characteristics
      including education, heroin use, route of drug administration, withdrawal
      symptoms, and craving. These groups also differed in opioid use during the four
      dosing weeks, with the lowest use in the 8 mg group and highest use in the 24 mg
      group (p < .0001). Additional analyses address withdrawal symptoms and craving.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Final week dose groups differed in
      demographic and drug use characteristics, and the group receiving the largest
      final week dose had the highest rate of continued opioid use. These findings may
      contribute to the development of clinical guidelines regarding buprenorphine dose
      in the treatment of opioid dependence; however, further investigations that
      include random assignment to dose by baseline characteristics are needed.

PMID- 21854291
TI  - Rates and influences of alcohol use disorder comorbidity among primary stimulant
      misusing treatment-seekers: meta-analytic findings across eight NIDA CTN trials.
AB  - BACKGROUND: There is need to improve treatment effectiveness for stimulant
      misusers, and one means of doing so is by tailoring services to account for
      common diagnostic comorbidities and psychosocial challenges they face.
      OBJECTIVES: Using its publicly available datasets, this CTN-approved secondary
      analysis project examined prevalence of alcohol use disorders (AUDs) among
      primary stimulant misusing treatment-seekers as well as impact of AUD comorbidity
      on their pre-treatment psychosocial functioning. METHODS: Upon identifying a
      primary stimulant misuser subsample (N = 1133) from among aggregated treatment
      seekers across eight CTN trials, diagnostic data were used to document lifetime
      AUD rates. Paired comparisons, stratified by stimulant drug type (e.g.,
      amphetamine, cocaine) then tested the influence of AUD comorbidity on
      psychosocial indices from the Addiction Severity Index - Lite. RESULTS: A high
      AUD rate (45%) was found in this client population. Among primary cocaine
      misusers, those with AUD were more likely to: (i) show elevated Addiction
      Severity Index composite scores, (ii) perceive greater importance of drug
      treatment, and (iii) endorse psychiatric symptoms and perceived need for their
      treatment. Among primary amphetamine misusers, those with AUD were more likely to
      endorse specific psychiatric symptoms. CONCLUSION: Study findings document AUD
      comorbidity as a fairly common diagnostic feature of primary stimulant misusers,
      and suggest it is a pervasive influence on the pre-treatment psychosocial
      functioning of cocaine misusers. SCIENTIFIC SIGNIFICANCE: This study demonstrates
      the utility of CTN common assessment battery for secondary analysis projects,
      though challenges noted during its conduct highlight the value of consistent data
      collection and documentation within and across CTN trials.

PMID- 21854293
TI  - Biofabrication of osteochondral tissue equivalents by printing topologically
      defined, cell-laden hydrogel scaffolds.
AB  - Osteochondral defects are prone to induce osteoarthritic degenerative changes.
      Many tissue-engineering approaches that aim to generate osteochondral implants
      suffer from poor tissue formation and compromised integration. This illustrates
      the need for further improvement of heterogeneous tissue constructs. Engineering
      of these structures is expected to profit from strategies addressing the
      complexity of tissue organization and the simultaneous use of multiple cell
      types. Moreover, this enables the investigation of the effects of three
      dimensional (3D) organization and architecture on tissue function. In the present
      study, we characterize the use of a 3D fiber deposition (3DF) technique for the
      fabrication of cell-laden, heterogeneous hydrogel constructs for potential use as
      osteochondral grafts. Changing fiber spacing or angle of fiber deposition yielded
      scaffolds of varying porosity and elastic modulus. We encapsulated and printed
      fluorescently labeled human chondrocytes and osteogenic progenitors in alginate
      hydrogel yielding scaffolds of 1*2 cm with different parts for both cell types.
      Cell viability remained high throughout the printing process, and cells remained
      in their compartment of the printed scaffold for the whole culture period.
      Moreover, distinctive tissue formation was observed, both in vitro after 3 weeks
      and in vivo (6 weeks subcutaneously in immunodeficient mice), at different
      locations within one construct. These results demonstrate the possibility of
      manufacturing viable centimeter-scaled structured tissues by the 3DF technique,
      which could potentially be used for the repair of osteochondral defects.

PMID- 21854294
TI  - Exploring and influencing the knowledge and attitudes of health professionals
      towards extended breastfeeding.
AB  - BACKGROUND: Although many U.S. professional health organizations have policy
      statements that support the breastfeeding of children beyond one year (extended
      breastfeeding), the actual attitudes of health workers towards this practice have
      not been explored. The purposes of this study were (1) to explore the knowledge
      and attitudes of various U.S. health professionals towards extended nursing and
      (2) to pilot an educational display for U.S. health professionals to promote
      their knowledge and attitudes towards extended breastfeeding. METHODS: A total of
      84 participants in a New York City academic medical center provided responses to
      a structured self-administered questionnaire given before and after an
      educational display. RESULTS: Respondents reported negative attitudes towards
      extended breastfeeding at baseline, with negative attitudes increasing as the age
      of the breastfed child increased. After education, the percentage of participants
      who found breastfeeding acceptable for 1- or 2-year-old children increased from
      61% to 89% (p < 0.001). Acceptability of 3- or 4-year-old children breastfeeding
      increased from 22% to 41% (p < 0.001). CONCLUSIONS: Viewing educational media
      concerning older nursing children may lead to more positive attitudes towards
      extended breastfeeding among healthcare professionals.

PMID- 21854292
TI  - Smoking cessation treatment among patients in community-based substance abuse
      rehabilitation programs: exploring predictors of outcome as clues toward
      treatment improvement.
AB  - BACKGROUND: Predictors of smoking cessation (SC) treatment outcome were explored
      in a multisite clinical trial of SC treatment at community-based, outpatient,
      substance abuse rehabilitation programs affiliated with the National Drug Abuse
      Treatment Clinical Trials Network. OBJECTIVES: To explore baseline demographic
      and clinical predictors of abstinence during treatment. METHODS: Cigarette
      smokers from five methadone maintenance programs and two drug and alcohol
      dependence treatment programs were randomly assigned to SC treatment as an
      adjunct to substance abuse treatment as usual or to substance abuse treatment as
      usual. SC treatment consisted of group counseling (weeks 1-8) plus transdermal
      nicotine patch treatment (21 mg/day, weeks 1-6; 14 mg/day, weeks 7-8).
      Demographic and clinical predictors of smoking abstinence were evaluated among
      those patients assigned to the active SC condition (N = 153) using logistic
      regression. RESULTS: Abstinence during treatment was positively associated with
      younger age, Hispanic or Caucasian (as opposed to African American)
      ethnicity/race, employment or student status, fewer cigarettes per day at
      baseline, lower severity of the primary substance problem at baseline, and higher
      methadone doses (among the subsample in methadone treatment). CONCLUSIONS AND
      SCIENTIFIC SIGNIFICANCE: During future efforts to improve SC treatments among
      drug- and alcohol-dependent patients, consideration should be given to adequate
      treatment to reduce the severity of the primary drug or alcohol problem,
      tailoring treatments for patients with greater severity of smoking and of the
      primary substance problem, and culturally sensitive interventions. Analysis of
      predictors of outcome may be a useful tool for treatment development.

PMID- 21854295
TI  - The free lunch is always an effective marketing tool: why WIC must change.

PMID- 21854296
TI  - Premature menopause: a comprehensive understanding of psychosocial aspects.
AB  - OBJECTIVE: To compare experience of premature menopause (PM), information
      sources, treatments, depression, anxiety, body image, sexual function and self
      efficacy, between women with premature ovarian failure (POF), surgically induced
      menopause (SIPM), chemically induced menopause (CIPM), and controls. DESIGN:
      Cross-sectional observational pilot study using validated and devised
      questionnaires in 77 Australian women (POF, n = 25; SIPM, n = 17; CIPM, n = 12;
      controls, n = 23). RESULTS: The average age of all women was 34.8 years (standard
      deviation (SD) +/- 5.7 years), and time since PM diagnosis was 3.8 years (SD +/-
      4.4 years, p = 0.19). The gynecologist (69%) and internet (67%) were the best
      expected sources of information. Women with PM feared osteoporosis more than
      controls (p < 0.0001). Women with SIPM (p = 0.006) and POF (p = 0.01) had higher
      rates of depression compared to controls. SIPM women were more anxious than women
      with POF (p = 0.04) and both SIPM (p = 0.002) and CIPM (p = 0.02) women were more
      anxious than controls. Women with POF had higher health evaluation (p = 0.03),
      fitness evaluation (p = 0.01) and fitness orientation (p = 0.01) than women with
      SIPM. Controls had higher health evaluation than women with SIPM (p = 0.001) and
      CIPM (p = 0.04), higher fitness evaluation than women with SIPM (p = 0.02) and
      CIPM (p = 0.04), and higher fitness orientation than SIPM women (p < 0.0001).
      Sexual dysfunction (p < 0.0001) and dyspareunia (p = 0.001) were higher in CIPM
      women than controls. Controls were more sexually responsive than POF women (p =
      0.008). SIPM (p = 0.008) and POF (p = 0.04) women reported decreased confidence
      to manage disease. CONCLUSION: Depression, anxiety, body image, sexual
      dysfunction and self-confidence are compromised for women across different groups
      of premature menopause. Understanding these differences is important to the
      development of individual management plans based on the needs of women.

PMID- 21854298
TI  - Assessment of the exposure to Allura Red colour from the consumption of red juice
      based and red soft drinks in Italy.
AB  - This article reports the results of a survey and an exposure study, based on a
      probabilistic approach, concerning red juice-based and red soft drink products in
      Italy. It highlights the fact that the estimates of both the consumption rates
      and colorant intakes are related to the hypotheses of scenarios. In fact, the
      study estimates that, on average, consumers of red soft drinks consume 53.1 L
      year(-1), ranging from 39.1 to 70.7 L of soft drink products under one scenario,
      or 21.3 L, and from 12.7 and 35.9 L under another hypothesis; while 9.5 L of red
      juice-based drinks are consumed per year, ranging from 7.0 to 12.5 L, under one
      scenario, or on average 6.9 L, and ranging from 3.2 to 17.7 L under another
      scenario. The amount of colorant in a red beverage ranged from 10.9 mg l(-1) in a
      red soft drink up to 55.9 mg l(-1) in a red juice-based product. The risk
      evaluation process showed that in all cases the intake of E129 was always lower
      than the acceptable daily intake. The exposure assessment showed high average
      intakes of Allura Red in the worst-case scenario, on average, 6.5 and 13.9 mg
      day(-1), up to 25.0 and 33.0 mg day(-1) at the 95th percentile, for juice-based
      and soft drinks respectively. The most realistic scenario estimated a weighted
      average daily intake of Allura Red, on average from about 0.3 to 0.5 mg day(-1)
      at the 95th percentile, and from 0.4 to 0.6 mg day(-1) for the 95th percentile,
      from juice-based and soft drinks, respectively. Actually, the highest colorant
      intake was estimated in a 'health' juice-based drink. The intake of E129
      significantly increased with a high level of colorant (>40 mg l(-1)).

PMID- 21854299
TI  - Eimeria involved in a case of coccidiosis in farmed red-legged partridges
      (Alectoris rufa) in France: oocyst isolation and gross lesion description after
      experimental infection.
AB  - The aim of the present work was, after a coccidiosis outbreak in a farm rearing
      red-legged partridges (Alectoris rufa) in Brittany (France), to identify the
      Eimeria species and describe gross lesions induced by three of them (Eimeria
      kofoidi, Eimeria caucasica and Eimeria legionensis) after experimental infection.
      E. kofoidi oocysts measured 19.3 um * 16.3 um on average; neither micropyle nor
      oocyst residuum were present, but one, two or more small polar granules were
      visible. After inoculation of 300,000 oocysts per partridge, severe gross lesions
      were observed in the duodenum and jejunum, characterized by thickened oedematous
      mucosa and lumen filled with thick mucus, gas and sometimes false-membrane due to
      sloughed epithelium. E. caucasica oocysts were on average 29.8 um * 19.5 um in
      size; no oocyst residuum was observed, but a large granule was well visible. E.
      caucasica also invaded both the duodenum and jejunum, causing haemorrhagic points
      on the serosal surface, as well as mucoid duodenitis and catarrhal enteritis when
      30,000 oocysts were inoculated per bird. E. legionensis oocysts measured 22.6 um
      * 14.9 um on average; they presented a clear micropyle beneath which one or two
      granulations were present. E. legionensis mainly invaded the caeca; low mortality
      was observed at the dosage of 200,000 oocysts per bird. Caecal walls were
      thickened and caseous material was condensed into off-white cheesy cores. For
      each species, oocyst shedding started 5 days post inoculation, peaked at 9, 8 and
      6 days post inoculation for E. kofoidi, E. caucasica and E. legionensis,
      respectively, then decreased and persisted until 15 days post inoculation (end of
      examinations).

PMID- 21854300
TI  - Modulating antibody pharmacokinetics using hydrophilic polymers.
AB  - INTRODUCTION: The use of hydrophilic polymers as a substitute for the Fc-domain
      in immuno- or non-immuno-based binding proteins is accelerating. Chemical
      PEGylation has led the way and is still the most advanced and clinically-approved
      approach. Hydrophilic polymers act by maintaining a flexible conformation and
      hydrogen bonding to a network of water molecules to acquire a larger hydrodynamic
      volume and apparent mass than their actual molecular mass suggest. The benefits
      are increased blood half-life and bioavailability, stability and reduced
      immunogenicity. In the case of PEG, there is also evidence of enhanced targeting
      and reduced side effects, but drawbacks include the fact that PEG is non
      biodegradable. AREAS COVERED: This report reviews the state of the art for
      antibody PEGylation in terms of approaches and effects. Additionally, non
      biological (such as N-(2-hydroxypropyl)methacrylamide) and potentially superior
      biological alternatives (such as polysialylation) are described, ending with
      recombinant approaches (such as hydrophilic peptides and glyco-engineering),
      which promise to circumvent the need for chemical modification altogether. EXPERT
      OPINION: The emergence of many small, antibody fragment-like mimics will drive
      the need for such technologies, and PEGylation is still the choice polymer due to
      its established use and track record. However, there will be a place for many
      alternative technologies if they can match the pharmacokinetics of PEG-conjugates
      and bring addition beneficial features such as easier production.

PMID- 21854301
TI  - Taribavirin in the treatment of hepatitis C.
AB  - INTRODUCTION: Treatment of chronic hepatitis C virus (HCV) is limited by
      substantial side effects including ribavirin-induced hemolytic anemia.
      Taribavirin, a ribavirin prodrug, was designed to concentrate within the liver to
      target HCV-infected hepatocytes while minimizing distribution within red blood
      cells (RBCs) and the subsequent development of hemolytic anemia. AREAS COVERED:
      The objective of the review is to evaluate the efficacy and safety of taribavirin
      as compared with ribavirin in the treatment of chronic HCV infections. A PubMed
      search was performed using the following key words: viramidine, taribavirin and
      ribavirin analog. Additional sources included press releases on preliminary
      results of clinical trials of taribavirin and abstracts presented at
      international meetings. The literature suggests that weight-based dosing of
      taribavirin at 25 mg/kg demonstrates lower rates of hemolytic anemia with
      comparable rates of sustained virologic response (SVR) and is the optimum dose
      for further studies comparing the efficacy of taribavirin with weight-based
      dosing of ribavirin. EXPERT OPINION: Failure to eradicate HCV may be associated
      with extrahepatic viral replication. The dosing strategy of taribavirin favors
      concentration within the liver to reduce treatment-limiting rates of anemia but
      may be insufficient to prevent virologic relapse.

PMID- 21854303
TI  - Could a vaccine against immune-evading cytomegalovirus become a reality?

PMID- 21854302
TI  - Potential benefits of allogeneic bone marrow mesenchymal stem cells for wound
      healing.
AB  - INTRODUCTION: It is becoming increasingly evident that select adult stem cells
      have the capacity to participate in repair and regeneration of damaged and/or
      diseased tissues. Mesenchymal stem cells have been among the most studied adult
      stem cells for the treatment of a variety of conditions, including wound healing.
      AREAS COVERED: Mesenchymal stem cell features potentially beneficial to cutaneous
      wound healing applications are reviewed. EXPERT OPINION: Given their potential
      for in vitro expansion and immune modulatory effects, both autologous and
      allogeneic mesenchymal stem cells appear to be well suited as wound healing
      therapies. Allogeneic mesenchymal stem cells derived from young healthy donors
      could have particular advantage over autologous sources where age and systemic
      disease can be significant factors.

PMID- 21854304
TI  - Provenge: combating prostate cancer with a vengeance?

PMID- 21854305
TI  - Study results show potential impact of rotavirus vaccine on hospitalization rates
      of children.

PMID- 21854306
TI  - Clinical evaluation of a soluble trimeric HIV-1 envelope glycoprotein vaccine.
AB  - Designing an HIV-1 envelope glycoprotein (Env) that can induce broadly
      neutralizing antibodies in humans remains one of the great challenges in
      biomedical research. Monomeric gp120 has repeatedly failed to induce cross
      neutralizing antibodies in clinical trials. Spearman et al. vaccinated uninfected
      volunteers with a trimeric gp140 protein. They found that the vaccine was safe
      and induced neutralizing antibody responses against the homologous virus, but not
      cross-neutralizing responses. The results reinforce the notion that our Env
      vaccine design needs to improve.

PMID- 21854307
TI  - Monitoring impact and effectiveness of rotavirus vaccination.
AB  - Rotavirus infection is the most common cause of severe gastroenteritis in
      children <5 years of age globally. Since 2009, the WHO has recommended inclusion
      of rotavirus vaccine in the national immunization programs of all countries. Data
      regarding rotavirus vaccine impact and effectiveness under conditions of routine
      use are important for encouraging countries to implement vaccination programs. In
      the absence of a national rotavirus vaccination program in France, the IVANHOE
      study was initiated to determine the real-world impact and effectiveness of
      rotavirus vaccine following introduction in a limited geographic area. This study
      found a twofold reduction in rotavirus hospitalizations among children <2 years
      of age who were age-eligible to receive rotavirus vaccine and a 98% vaccine
      effectiveness, highlighting the health benefits of a vaccination program.

PMID- 21854308
TI  - Efficacy and correlates of protection for cell culture-derived and egg-derived
      inactivated influenza vaccines in younger adults.
AB  - The randomized, double-blind, placebo-controlled efficacy study by Barrett et al.
      demonstrated the efficacy of cell culture-derived trivalent inactivated influenza
      vaccine (TIV), as manufactured by Baxter BioScience, in healthy adults 18-49
      years of age. Efficacy and safety was comparable to that demonstrated by other
      recent randomized, placebo-controlled studies of cell culture-derived and egg
      derived TIV in younger adults. The principal advantage of cell culture
      manufacturing of influenza vaccine relates to pandemic preparedness, although
      some advantages exist for seasonal vaccine production. The Barrett study
      confirmed a correlation between anti-hemagglutinin serum antibody and protection
      from influenza. However, further analysis of the correlation appears warranted in
      the Barrett study and in future studies to better describe antibody-induced and
      vaccine-induced protection from influenza illness.

PMID- 21854309
TI  - Protective efficacy of live-attenuated influenza vaccine (multivalent, Ann Arbor
      strain): a literature review addressing interference.
AB  - Selecting the B strain for inclusion in a trivalent seasonal influenza vaccine
      has been difficult because two distinct influenza B lineages frequently co
      circulate, prompting consideration of a quadrivalent vaccine containing two A and
      two B strains. Because interference among wild-type influenza viruses is a well
      documented phenomenon and viral replication is required to elicit protection by
      the licensed live-attenuated influenza vaccine (LAIV; MedImmune, LLC,
      Gaithersburg, MD, USA), a potential quadrivalent formulation raises
      considerations of interference among the LAIV strains contained in the vaccine.
      We reviewed the available clinical and nonclinical literature to understand the
      potential impact of viral interference on immunogenicity, efficacy and shedding
      of LAIV strains. We have found no clinically significant evidence of viral or
      immune interference affecting efficacy of LAIV strains in multivalent vaccine
      formulations. Future clinical studies should compare the safety and immune
      responses of children and adults to licensed trivalent and investigational
      quadrivalent LAIV formulations.

PMID- 21854310
TI  - Intradermal naked plasmid DNA immunization: mechanisms of action.
AB  - Plasmid DNA is a promising vaccine modality that is regularly examined in prime
      boost immunization regimens. Recent advances in skin immunity increased our
      understanding of the sophisticated cutaneous immune network, which revived
      scientific interest in delivering vaccines to the skin. Intradermal
      administration of plasmid DNA via needle injection is a simple and inexpensive
      procedure that exposes the plasmid and its encoded antigen to the dermal immune
      surveillance system. This triggers unique mechanisms for eliciting local and
      systemic immunity that can confer protection against pathogens and tumors.
      Understanding the mechanisms of intradermal plasmid DNA immunization is essential
      for enhancing and modulating its immunogenicity. With regard to vaccination, this
      is of greater importance as this routine injection technique is highly desirable
      for worldwide immunization. This article will focus on the current understanding
      of the mechanisms involved in antigen expression and presentation during primary
      and secondary syringe and needle intradermal plasmid DNA immunization.

PMID- 21854311
TI  - The future of cell culture-based influenza vaccine production.
AB  - Influenza vaccines have been prepared in embryonated chicken eggs and used for
      more than 60 years. Although this older technology is adequate to produce
      hundreds of millions of doses per year, most viral vaccines are now being
      produced in cell culture platforms. The question of whether egg-based influenza
      vaccines will continue to serve the needs of the growing influenza vaccine market
      is considered here. In 2006, the US government committed to support the
      development of cell-based influenza vaccines by funding advanced development and
      expansion of domestic manufacturing infrastructure. Funding has also been
      provided for other recombinant DNA approaches that do not depend on growth of
      influenza viruses. As the influenza vaccine industry expands over the next 5-10
      years, it will be interesting to follow which of these various technologies are
      able to best meet the needs of a growing influenza vaccine market.

PMID- 21854312
TI  - Assessing vaccination coverage in the European Union: is it still a challenge?
AB  - Assessing vaccination coverage is of paramount importance for improving quality
      and effectiveness of vaccination programs. In this article, some of the different
      systems that are used for assessing vaccination coverage within and outside the
      EU are reviewed in order to explore the need for improving vaccination coverage
      data quality. All countries in the EU have implemented vaccination programs for
      children, which include vaccinations to protect against between nine and 14
      infectious diseases. Collecting and assessing vaccination coverage regularly is
      part of such programs, but the methods used vary widely. Some quality issues are
      evident when data reported through administrative methods are compared with
      seroprevalence studies or other surveys. More thorough assessment of vaccination
      coverage and more effective information sharing are needed in the EU. A
      homogeneous system for assessing vaccination coverage would facilitate
      comparability across countries and might increase the level of the quality of
      both the national and local systems. Cooperative and coordinated responses to
      vaccine-preventable disease threats might be improved by better information
      sharing.

PMID- 21854313
TI  - Outlining novel cellular adjuvant products for therapeutic vaccines against
      cancer.
AB  - Despite the library of new adjuvants available for use in vaccines, we remain, at
      present, almost reliant on aluminum-based compounds for clinical use. The
      increasing use of recombinant subunit vaccines, however, makes the need for
      improved adjuvant of particular interest. Adjuvants are crucial components of all
      cancer vaccines whether they are composed of whole cells, proteins or peptides.
      For the purposes of this article, cellular adjuvant products are defined as
      adjuvants associated with cellular or T-cell immunity. Several pharmaceutical
      companies are developing new adjuvants or immune enhancers for the treatment of
      cancers such as melanoma and non-small-cell lung carcinoma. Several products are
      being developed and have entered clinical trials either alone or in combination.
      In this article, we discuss recent adjuvant development and novel cellular
      adjuvant products for therapeutic cancer vaccines.

PMID- 21854316
TI  - Retraction. Various carrier system(s)-mediated genetic vaccination strategies
      against malaria.

PMID- 21854317
TI  - The application of errorless learning to aphasic disorders: A review of theory
      and practice.
AB  - Recently, there has been great interest in errorless learning as a new
      intervention technique. This may be because there are data from both basic
      neuroscience and clinical application that suggest it is superior to more
      traditional trial and error methods. In the contemporary literature the most
      prominent investigations of errorless learning are those designed for
      rehabilitation of memory impairments. These studies include numerous
      demonstrations of effective amelioration of word finding difficulties using
      errorless intervention. The aphasic literature contains no examples of purely
      errorless learning methods, however, some studies have successfully treated
      anomia using error reducing techniques. This suggests that errorless learning
      could be advantageous for treating aphasic disorders, in particular anomia. To
      explore this idea, we discuss previous research and review two current theories
      of errorless learning. We provide our own framework for thinking about errorless
      and errorful learning. In addition, a review of the anomia treatment literature
      (from 1985 to the present) is presented and conclusions drawn on the methods of
      treating the word finding difficulties of patients with aphasia.

PMID- 21854318
TI  - Effects of cigarette smoking on reward responsivity and cognitive function in
      brain injured individuals.
AB  - Abstinence from smoking has been associated with acute impairments of performance
      in a number of tasks associated with incentive motivation and executive
      functioning in non-injured participants. The current study aimed to investigate
      the effects of smoking on various cognitive and motivational measures in 18 brain
      injured smokers, thus generalising previous findings from non-injured
      participants. A within-subjects cross-over design was utilised, to compare
      performance after an acute period of abstinence from smoking with performance
      after smoking. The test battery included measures of reward responsivity (a card
      sorting task providing a behavioural index of incentive motivation), verbal
      fluency, and working memory. Reward responsivity was enhanced after a cigarette
      had been smoked compared to when abstinent. Performance on the card sorting task
      was particularly enhanced when the task was novel. There was no significant
      enhancement on any other measure. It was concluded that smoking has a direct
      effect on responsiveness to incentive, which we have found elsewhere to be
      closely related to motivation in therapy. Implications for clinical
      neuropsychological assessment and treatment are discussed.

PMID- 21854319
TI  - The quantity of life for people with chronic aphasia.
AB  - This study sought to examine the relationships between social activity and
      aphasia. Thirty-eight people with chronic aphasia and their closest relative
      completed a newly developed Social Network with Aphasia Profile (SNAP) and
      relatives completed a Communicative Effectiveness Index (CETI) during the summer
      months of the year 2000. The SNAP requires a record to be kept over a consecutive
      seven-day period of who the person with aphasia sees (e.g., doctor, brother),
      where they see them (e.g., hospital, gym, pub), and why (e.g., to attend group
      meeting, shopping). A multiple regression analysis was carried out using the
      number of hours people spent out of their home as the independent variable, and
      severity of aphasia, age, time since onset and presence of hemiplegia as
      dependent variables. This accounted for 30% of the variance and revealed that
      severity of aphasia has a particularly negative impact. Age and physical
      condition also have a negative impact. However, a rich social network was
      observed for some aphasic people. Only one participant was receiving speech
      language therapy of two hours per week. Implications for reducing communication
      barriers, raising public awareness and service provision are discussed.

PMID- 21854320
TI  - Rehabilitation of unilateral neglect in the acute recovery stage: The efficacy of
      limb activation therapy.
AB  - Unilateral neglect has been shown to dissociate into three areas of space:
      personal, peripersonal, and locomotor. Robertson, Hogg, and McMillan (1998)
      showed that movement of the contralesional limb (limb activation therapy) reduced
      neglect in a patient 18 months after brain injury. However, the beneficial
      effects of treatment were only maintained in peripersonal space. This study
      replicated and extended the work of Robertson et al. (1998) to evaluate limb
      activation therapy at a more acute stage of recovery. A single case ABABA design
      was used with a patient 8 weeks post-stroke. No significant overall treatment
      effect was observed. However, a significant effect of the first treatment phase
      was seen in peripersonal and locomotor space. This improvement was maintained in
      locomotor space, but not in peripersonal space. This study provides tentative
      support for the efficacy of limb activation therapy at an acute stage of
      recovery. However, more research is needed to strengthen this conclusion and
      clarify the generalisability of the observed effects.

PMID- 21854314
TI  - Vaccinia viruses: vaccines against smallpox and vectors against infectious
      diseases and tumors.
AB  - Less than 200 years after its introduction, widespread use of vaccinia virus
      (VACV) as a smallpox vaccine has eradicated variola virus. Along with the
      remarkable success of the vaccination program, frequent and sometimes severe
      adverse reactions to VACV were encountered. After eradication, VACV has been
      reserved for select populations who might be at significant risk for
      orthopoxvirus infections. Events over the past decade have renewed concerns over
      the potential use of variola virus as a biological weapon. Accordingly, interest
      in VACV and attenuated derivatives has increased, both as vaccines against
      smallpox and as vectors for other vaccines. This article will focus on new
      developments in the field of orthopoxvirus immunization and will highlight recent
      advances in the use of vaccinia viruses as vectors for infectious diseases and
      malignancies.

PMID- 21854321
TI  - Research digest.
AB  - Deactivations in Functional Neuroimaging: When "REST" is anything but restful
      Pharmacological approaches to Neuropsychological Rehabilitation.

PMID- 21854325
TI  - The three vectors of consciousness and their disturbances after brain injury.
AB  - Based on the recent review of Zeman (2001) three "vectors" of consciousness
      aredescribed. A model for understanding how they are related is outlined.
      Recentbehavioural and neuroimaging studies are reviewed pertinent to this
      conceptualisation. Initial ideas for working with these disturbances in
      consciousness during neuropsychological rehabilitation are presented.

PMID- 21854322
TI  - Associations of asthma with body mass index and adult weight change among
      reproductive age women.
AB  - OBJECTIVE: To evaluate the cross-sectional relationship between asthma and pre
      gravid body mass index (BMI), and to assess the risk of adult weight change among
      women with history of asthma diagnosed in childhood or adulthood, respectively.
      STUDY DESIGN: Study participants were 3737 pregnant women enrolled in a cohort
      study. Information on history of asthma, pre-gravid BMI, adult weight change
      (difference between BMI at age 18 and pre-gravid BMI), and other sociodemographic
      characteristics was collected using interviewer-administered questionnaires. Pre
      gravid BMI was categorized into lean (BMI < 18.5 kg/m(2)), overweight (BMI = 25
      24.9 kg/m(2)), and obese (BMI >= 30 kg/m(2)). Logistic regression was used to
      estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:
      Approximately 13.1% of study participants reported history of asthma. Compared
      with the reference group (BMI = 18.5-24.9 kg/m(2)), the odds of asthma was higher
      among overweight (OR = 1.51; 95% CI = 1.18-1.93) and obese (OR = 1.47; 95% CI =
      1.06-2.03) women while it was lower among lean women (OR = 0.42; 95% CI = 0.21
      0.84) (trend p-value <.001). Women who gained >=20 kg compared with those who
      maintained their weight (+/-2.5 kg) had a 2.7-fold increased odds of asthma (95%
      CI = 1.02-7.00). CONCLUSIONS: Overweight and obese women were more likely to have
      a history of asthma. Adult weight gain was positively associated with asthma
      diagnosis. Longitudinal studies designed to prospectively assess patterns of
      adult weight change in relation to asthma are warranted.

PMID- 21854326
TI  - Mild traumatic brain injury: Impairment and disability assessment caveats.
AB  - Mild traumatic brain injury (MTBI) accounts for approximately 80% of all brain
      injuries, and persistent sequelae can impede physical, emotional, social,
      marital, vocational, and avocational functioning. Evaluation of impairment and
      disability following MTBI typically can involve such contexts as social security
      disability application, personal injury litigation, worker's compensation claims,
      disability insurance policy application, other health care insurance policy
      coverage issues, and the determination of vocational and occupational
      competencies and limitations. MTBI is still poorly understood and impairment and
      disability assessment in MTBI can present a significant diagnostic challenge.
      There are currently no ideal systems for rating impairment and disability for
      MTBI residua. As a result, medicolegal examiners and clinicians must necessarily
      familiarise themselves with the variety of disability and impairment evaluation
      protocols and understand their limitations. The current paper reviews recommended
      procedures and potential obstacles and confounding issues.

PMID- 21854323
TI  - Adolescent decision-making about use of inhaled asthma controller medication:
      results from focus groups with participants from a prior longitudinal study.
AB  - BACKGROUND: Adherence with inhaled controller medications for asthma is known to
      be highly variable with many patients taking fewer doses than recommended for
      consistent control of lung inflammation. Adherence also worsens as children
      become teenagers, although the exact causes are not well established. OBJECTIVE:
      To use focus group methodology to examine beliefs, feelings, and behaviors about
      inhaled asthma controller medication in adolescents and young adults who had
      previously participated in a longitudinal study of asthma treatment adherence and
      outcome in order to develop more effective management strategies. METHODS: Twenty
      six subjects participated in 6 focus groups comprised of 3-5 young adults (age
      range 12-20 years). Verbatim transcripts of these groups were analyzed using the
      long-table method of content analysis to identify key themes raised by
      participants. RESULTS: A variety of beliefs, feelings, and behaviors influence
      the adolescent's decision about how to use their asthma medication. Some of the
      adolescents understood the importance of daily medication and were committed to
      the treatment plan prescribed by their provider. Poorer adherence was the product
      of misinformation, incorrect assumptions about their asthma, and current life
      situations. CONCLUSIONS: These results, by highlighting potential mechanisms
      underlying both better and worse adherence, inform the development of strategies
      to improve adherence behavior in adolescents and young adults with asthma.
      Knowledge of the specific beliefs, feelings, and behaviors that underlie
      adolescents' use of inhaled asthma controller medication will help providers
      maximize treatment adherence in this notoriously difficult patient population.

PMID- 21854327
TI  - Impact of pre-injury factors on outcome after severe traumatic brain injury: Does
      post-traumatic personality change represent an exacerbation of premorbid traits?
AB  - Although personality change is a frequent and disabling consequence of severe
      degrees of traumatic brain injury (TBI), little information is available beyond
      descriptive statements. The present paper presents a brief overview of the
      literature on the effects of pre-injury variables on post-trauma psychosocial
      functioning, and makes specific examination of the effect of premorbid
      personality structure on the post-trauma personality in people with TBI. A close
      relative of 28 people undergoing rehabilitation after TBI completed the Eysenck
      Personality Questionnaire Revised (EPQ-R) and Current Behaviour Scale (CBS)
      regarding the injured person's personality and character. Data were collected on
      three occasions: Ratings about premorbid status were taken as soon as feasible
      after admission, and follow-up ratings regarding current status were made at 6and
      12 months post-trauma. As a group, premorbid ratings indicated an unremarkable
      profile on the EPQ-R. Significant changes had occurred by 6months post-trauma,
      which were sustained at 12 months post-trauma for both the EPQ-R and CBS. Yet
      none of the specific hypotheses regarding premorbid personality structure on the
      EPQ-R and post-trauma characterological deficits on the two CBS factors, Loss of
      Emotional Control (LEC) and Loss of Motivation (LM), was supported: There were no
      significant differences between subgroups with high or low premorbid levels of
      Extraversion, Neuroticism, Psychoticism, Addiction and Criminality and post
      trauma CBS factors, LEC, and LM. These findings suggest that although personality
      changes occur as a result of traumatic brain injury, they are largely independent
      of the premorbid personality structure.

PMID- 21854328
TI  - The neuropsychiatry of depression after brain injury.
AB  - Biological aspects of depression after brain injury, in particular traumatic
      brain injury (TBI) and stroke, are reviewed. Symptoms of depression after brain
      injury are found to be rather non-specific with no good evidence of a clear
      pattern distinguishing it from depression in those without brain injury.
      Nevertheless symptoms of disturbances of interest and concentration are
      particularly prevalent, and guilt is less evident. Variabilitiy of mood is
      characteristic. The prevalence of depression is similar after both stroke and TBI
      with the order of 20-40% affected at any point in time in the first year, and
      about 50% of people experience depression at some stage. There is no good
      evidence for areas of specific vulnerability in terms of lesion location, and
      early suggestions of a specific association with injury to the left hemisphere
      have not been confirmed. Insight appears to be related to depressed mood with
      studies of TBI indicating that greater insight over time post-injury may be
      associated with greater depression. We consider that this relationship may be due
      to depression appearing as people gain more awareness of their disability, but
      also suggest that changes in mood may result in altered awareness. The risk of
      suicide after TBI is reviewed. There appears to be about a three to fourfold
      increased risk of suicide after TBI, although much of this increased risk may be
      due to pre-injury factors in terms of the characteristics of people who suffer
      TBI. About 1% of people who have suffered TBI will commit suicide over a 15-year
      follow-up. Drug management of depression is reviewed. There is little specific
      evidence to guide the choice of antidepressant medication and most psychiatrists
      would start with a selective serotonin reuptake inhibitor (SSRI). It is important
      that the drug management of depression after brain injury is part of a full
      package of care that can address biological as well as psychosocial factors in
      management.

PMID- 21854330
TI  - The relevance of emotional and psychosocial factors in aphasia to rehabilitation.
AB  - In this paper we review the relationship between the impact of aphasia and
      emotional well-being. Depression is one of several types of emotional response
      that has been researched most and we examine the different causes of depression
      for people with aphasia. We discuss the relationships between recovery and
      emotional state and the clinical and psychosocial implications of these
      relationships. We examine methods for assessment of emotional response and
      psychosocial evaluation and review implications for rehabilitation. We discuss
      briefly issues of drug treatment for depression in aphasic people. We conclude
      that the emotional impact of aphasia can have a marked negative impact on
      recovery, response to rehabilitation, and psychosocial adjustment.

PMID- 21854329
TI  - Cognitive behaviour therapy for the treatment of depression in individuals with
      brain injury.
AB  - This article focuses on depression and its psychological management following
      brain injury or stroke in the adult population. The presentation of depression in
      the context of brain injury is discussed and a summary of the psychosocial
      aetiological factors for the development of depression in this context is
      provided. The links between depression and neuropsychological functioning are
      explored and the significant impact of depression on neurorehabilitation outcome
      highlights the need for the development of effective interventions in this area.
      Cognitive behaviour therapy (CBT) is presented as a potentially suitable
      treatment: The model is described with ideas for the clinician on how to adapt
      the delivery of CBT for clients with neuropsychological impairment. To date,
      there have been a very small number of studies evaluating CBT for the treatment
      of depression in brain injury, however their results have been promising. It is
      concluded that further research is necessary.

PMID- 21854331
TI  - Neurorehabilitation and cognitive-behaviour therapy of anxiety disorders after
      brain injury: An overview and a case illustration of obsessive-compulsive
      disorder.
AB  - Survivors of acquired and traumatic brain injuries may often experience anxiety
      states. Psychological reactions to neurological trauma may be caused by a complex
      interaction of a host of factors. We explore how anxiety states may be understood
      in terms of a biopsychosocial formulation of such factors. We also review the
      current evidence for the presence of specific anxiety disorders after brain
      injury. We then describe how cognitive-behaviour therapy (CBT), a treatment of
      choice for many anxiety disorders, may be integrated with cognitive
      rehabilitation (CR), for the management of anxiety disorders in brain injury. We
      illustrate how CBT and CR may be delivered with a case of a survivor of traumatic
      brain injury (TBI) who had developed obsessive compulsive disorder and health
      anxiety. We show how CBT plus CR allows a biopsychosocial formulation to be
      developed of the survivor's concerns for guiding a goal-based intervention. The
      survivor made significant gains from intervention in terms of goals achieved and
      changes on clinical measures. We argue that large-scale research is needed for
      developing an evidence base for managing emotional disorders in brain injury.

PMID- 21854332
TI  - Post-traumatic stress disorder and traumatic brain injury: A review of causal
      mechanisms, assessment,and treatment.
AB  - In this paper we explore the evidence for post-traumatic stress disorder (PTSD)
      after traumatic brain injury (TBI). We examine its possible mediating mechanisms
      after brain injury, the evidence for its occurrence, risk, and protective
      factors, and the implications for intervention and service demands. In the first
      section we review the current literature relevant to cause, maintenance, and
      treatment of PTSD in general, before addressing issues associated with the
      assessment and management of PTSD after TBI. It is argued that PTSD may occur
      after a brain injury, and can be, relatively, a common disorder. However,
      explanatory mechanisms for its occurrence may be speculative. In this context, we
      argue, assessment and treatment need to be carefully considered, and
      comprehensive.

PMID- 21854333
TI  - Traumatic brain injury and substance abuse: A review and analysis of the
      literature.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability
      worldwide. Accidents are a major cause of brain injury, and many accidents are
      alcohol or drug related. Evidence indicates that a vast majority of victims test
      positive for alcohol or illicit drugs at the time of hospital admission. Research
      also suggests that a majority of TBI survivors were moderate to heavy drinkers
      pre-injury. This manuscript reviews literature on pre- and post-injury substance
      use patterns, abuse risk factors, and dangers of post-injury use. Assessment is
      discussed in detail with information provided on the need for quantitative
      assessment, records review, corroboration, and long-term monitoring. Information
      is also provided on critical features of treatment, prevention, and education,
      and on the role of psychologists in substance abuse assessment and treatment. The
      manuscript concludes with a section addressing issues, questions, and concerns
      commonly encountered by clinicians.

PMID- 21854334
TI  - Pain following traumatic brain injury: Assessment and management.
AB  - Traumatic brain injury is frequently associated with painful complaints
      immediately after injury and subsequently. Early assessment of possible painful
      conditions can be made at the time of physical examination in those who are
      unable to give a history. Non-verbal signs of pain, including withdrawal of a
      painful limb or body part, irritability or tears should draw the attention of the
      assessing physician to a peripheral painful site. Treatment of conditions giving
      rise to pain can be made at this stage. Persistent pain may arise from a
      combination of physical and psychological factors and is best managed in a
      multidisciplinary pain clinic. Contributions from physicians in pain management,
      psychologists, physiotherapists and clinical nurse specialists enable a
      rehabilitation programme to take place. Treatments include analgesic drugs,
      graded exercise, cognitive-behavioural therapy, and transcutaneous electrical
      nerve stimulation. Rehabilitation of people who have ahead injury and pain takes
      longer than usual and separate pain management facilities should be developed for
      this population.

PMID- 21854335
TI  - Contemporary approaches to the management of irritability and aggression
      following traumatic brain injury.
AB  - In this paper, the principal means of managing irritability and aggression
      following traumatic brain injury (TBI) will be briefly reviewed. The paper will
      initially consider the prevalence of irritability, what it is and some of the
      likely causes that drive the condition. Aggression will then be similarly
      contemplated. Prior to a discussion regarding those methods most regularly
      employed in their management, the attention of the reader will be directed to a
      range of methodological issues that need to be considered in relation to
      reporting treatment efficacy, including lack of homogeneity and the need to use
      standardised assessment tools. Three principal management approaches will then be
      described and appraised, these being pharmacology, psychotherapy, and behaviour
      therapy. Within the discussion of psychotherapeutic methods, special mention will
      be made with regard to use of cognitive behaviour therapy, and two detailed case
      studies will be employed to illustrate issues relating to both cognitive
      behaviour therapy and behaviour therapy.

PMID- 21854336
TI  - Episodic disorders of behaviour and affect after acquired brain injury.
AB  - Psychological disorders that follow traumatic brain injury are possibly more
      complex and diverse than those associated with other forms of "brain damage".
      These may include organic aggressive, or organic affective syndromes that are
      episodic in nature and therefore require a more specific diagnosis, a different
      classification, and a different approach to treatment. Consequently, it is
      necessary for clinicians to learn to distinguish between "primary" psychiatric
      illnesses and those disorders of behavioural control and mood that stem
      specifically from brain injury. There is relatively little in the clinical
      literature that explains the relationship between variable states of behaviour,
      mood or temperament, and clinical disorders that may have long-term implications
      for patient management. This concept paper therefore addresses abnormalities of
      mood and behaviour that are episodic in character and are not recognisably
      included in the DSM and ICD classifications of psychological or psychiatric
      disorders.

PMID- 21854337
TI  - Intervention with families following brain injury: Evidence-based practice.
AB  - The literature on brain injury and the family is examined to provide an evidence
      base for family intervention. In the absence of methodologically sound studies
      which evaluate the efficacy of family intervention, current practice should be
      based on the findings of studies that have investigated how families adapt and
      the difficulties they face in this process. The implications of this literature
      should be considered at all stages in the rehabilitation process and in all forms
      of contact with the family.

PMID- 21854338
TI  - Sexual changes associated with traumatic brain injury.
AB  - Findings from numerous outcome studies have suggested that people with traumatic
      brain injuries (TBI) experience relationship difficulties and changes in
      sexuality. However, there have been few investigations of these problems. This
      paper reports the results of a study of sexuality following TBI, which aimed to
      identify changes in sexual behaviour, affect, self-esteem, and relationship
      quality, and their inter-relationships. Two hundred and eight participants with
      moderate-to-severe TBI (69% males) completed a questionnaire 1-5 years post
      injury. Their responses were compared with those of 150 controls, matched for
      age, gender, and education. Of TBI participants 36-54% reported: (1) A decrease
      in the importance of sexuality, opportunities, and frequency of engaging in
      sexual activities; (2) reduced sex drive; (3) a decline in their ability to give
      their partner sexual satisfaction and to engage in sexual intercourse; and (4)
      decreased enjoyment of sexual activity and ability to stay aroused and to climax.
      The frequencies of such negative changes were significantly higher than those
      reported by controls and far outweighed the frequency of increases on these
      dimensions. A significant proportion of TBI participants also reported decreased
      self-confidence, sex appeal, higher levels of depression, and decreased
      communication levels and relationship quality with their sexual partner. Factors
      associated with sexual problems in the TBI group are explored and implications of
      all findings discussed.

PMID- 21854339
TI  - Psychological adjustment, social enablement and community integration following
      acquired brain injury.
AB  - Understanding and facilitating the process of psychological adjustment to
      acquired disability arising from brain injury continues to pose a considerable
      challenge to rehabilitation professionals. This paper reviews the literature on
      psychological adjustment to acquired disability and chronic health conditions as
      they may be applied to acquired brain injury. It is proposed that services are
      developed that address the psychosocial issues faced by survivors of brain
      injury. Case illustrations are provided that demonstrate a process of adjustment
      and integration towards participation in meaningful roles within the community.

PMID- 21854340
TI  - Rehabilitation of the emotional problems of brain disorders in developing
      countries.
AB  - Emotional and behavioural problems of people with brain disorders are major
      undertreated problems in developing countries. These can be addressed by training
      lay volunteers in community-based rehabilitation. Training and pro gramme
      implementation must be highly sensitive to local conditions. Basic concepts that
      can be trained in such conditions include case finding, triage, evaluation
      skills, emotional rehabilitation, restoration and compensation strategies, the
      continuum of responsibility, the zone of recovery, scaffolding, adjusting the
      person-environment fit, awareness of deficits, setting goals, communicating with
      others about the disability, disability rights, support groups, and circles of
      support.

PMID- 21854341
TI  - Children's and parents' report of asthma education received from physicians.
AB  - OBJECTIVE: Clinical practice guidelines recommend that physicians provide asthma
      education to patients and their families. To characterize parents' and children's
      perception of physician practice, we examined: (i) proportion of parents and
      children reporting physician discussion of asthma education topics; (ii) age
      group differences in children's report; (iii) site differences in children's and
      parents' report; (iv) sociodemographic and disease characteristics associated
      with children's report; and (v) the relation between children's report and
      adherence to daily controller medications. METHODS: We conducted a cross
      sectional study of 125 children with asthma (mean age = 11.3 years; 62% were
      male) and their parents. Parents provided demographic and disease data. Children
      reported whether physicians had ever discussed each of 16 asthma education topics
      with them. We used logistic regression to examine age-group and site differences
      in children's report of physician discussion of each topic. Multivariate linear
      regression was used to determine associations between demographic (e.g., child
      age, race) and disease (e.g., symptom severity) variables and topics discussed.
      RESULTS: On average, 34.7% of children reported physician discussion of a topic;
      8-10-year-olds reported significantly fewer topics discussed than children aged
      11 and older (p < .05). Whereas parents' report differed by practice setting,
      children's report did not. In multivariate analyses, child age (beta = 0.46 (SE:
      0.17); p < .01), persistent symptoms (beta = 1.59 (SE: 0.80); p < .05), and
      number of outpatient asthma visits (beta = 0.19 (SE: 0.08); p < .05) remained
      significantly associated with number of topics discussed. CONCLUSION: These
      results suggest that the majority of children either may not receive, or may not
      recall receiving, information from their physicians about the fundamentals of
      asthma management. Physicians have an invaluable teaching opportunity in the
      medical office visit and should consider capitalizing on this opportunity to
      build children's sense of self-efficacy and competence in their self-care.

PMID- 21854342
TI  - Effects of inhaled mometasone furoate on growth velocity and adrenal function: a
      placebo-controlled trial in children 4-9 years old with mild persistent asthma.
AB  - OBJECTIVE: To assess the effects of long-term mometasone furoate delivered via a
      dry powder inhaler (MF-DPI) on growth velocity and hypothalamic-pituitary-adrenal
      axis function in children with asthma. STUDY DESIGN: Children aged 4-9 years with
      asthma (n = 187) were randomized to MF-DPI 100 MUg (delivered dose; actuated dose
      is 110 MUg) once daily in the morning (QD AM), 100 MUg twice daily (BID), 200 MUg
      QD AM, or placebo for 52 weeks followed by a 3-month follow-up period. The
      primary outcome was growth velocity calculated from stadiometric heights recorded
      at each visit. Secondary outcomes included serum and 12-h urinary cortisol, serum
      osteocalcin, and urinary N-telopeptide. RESULTS: MF-DPI 100 MUg QD AM treatment
      did not significantly affect growth velocity compared with placebo (-0.10 +/-
      0.31 cm/y, p = 0.76). When the effect of a total daily dose of 200 MUg MF-DPI on
      growth velocity was examined, no significant effect was demonstrated for MF-DPI
      100 MUg BID compared with placebo (-0.64 +/- 0.39 cm/y, p = 0.10), although the
      change in mean growth velocity with MF-DPI 200 MUg QD AM reached statistical
      significance (-0.70 +/- 0.29 cm/y, p = 0.02). The effects of all examined doses
      of MF-DPI on mean plasma cortisol levels were similar to cortisol changes seen in
      the placebo group, suggesting an absence of drug-related effects. No differences
      in 12-h urinary cortisol or other outcomes were observed between groups.
      CONCLUSIONS: One year of treatment with a total daily dose of 100 MUg of MF-DPI
      in the morning resulted in no significant difference, whereas a total daily dose
      of 200 MUg of MF-DPI was associated with some changes in growth velocity when
      compared with placebo. The differences in growth velocity, and the absence of
      drug-related cortisol effects, support the use of a total daily dose of 100 MUg
      of MF-DPI in children aged 4-9 years with mild persistent asthma.

PMID- 21854343
TI  - IgG immune complex induces the recruitment of inflammatory cells into the airway
      and TNF-mediated late airway hyperresponsiveness via NF-kappaB activation in
      mice.
AB  - BACKGROUND: Many of the inflammatory proteins that are expressed in asthmatic
      airways are regulated, at least partially, by nuclear factor (NF)-kappaB.
      Blockade of NF-kappaB activity has resulted in attenuation of the cardinal
      features of asthma. Thus, delineating the mechanisms involved in NF-kappaB
      activation in asthma might provide an interesting approach to improving the
      management of asthma. However, despite its importance, the mechanism for NF
      kappaB activation in asthma has not yet been determined. OBJECTIVE: To examine
      the role of IgE and IgG antibodies (Abs) in the activation of NF-kappaB in mouse
      lungs. METHODS: To examine the effect of IgE, mice underwent intratracheal (i.t.)
      instillation of an IgE immune complex (IgE-IC) (anti-2,4-dinitrophenyl hapten
      (DNP) IgE + DNP-BSA or DNP-OVA) and anaphylactogenic anti-IgE (LO-ME-2). For IgG,
      mice underwent i.t. instillation with a complex of anti-chicken gamma globulin
      (CGG) IgG1 mAb + CGG. NF-kappaB activation was determined by gel shift assay.
      Small interfering RNA was used for blockade of p50 expression. The effect of
      tumor necrosis factor (TNF) blockade was determined using anti-TNF Ab. A
      previously established murine model of asthma was used to assess airway
      hyperresponsiveness (AHR). RESULTS: A single i.t. instillation of either IgE-IC
      or LO-ME-2 failed to induce activation of NF-kappaB in the lungs. In contrast,
      single i.t. instillation of IgG-IC was capable of inducing NF-kappaB activation,
      as well as NF-kappaB-dependent proinflammatory molecules, such as TNF and CXC
      chemokines. Pretreatment of p50 small interfering RNA decreased bronchoalveolar
      lavage fluid levels of TNF and macrophage inflammatory protein-2 induced by IgG
      IC instillation. Single i.t. instillation of IgG-IC caused the recruitment of
      neutrophils and macrophages into the airway and TNF-mediated late AHR, but failed
      to induce Th2 cell-mediated asthmatic phenotypes. CONCLUSION: IgG, but not IgE,
      is the major Ab that induces not only NF-kappaB activation and NF-kappaB
      dependent proinflammatory molecules in the lungs but also subsequent recruitment
      of inflammatory cells into the airway and TNF-mediated late AHR.

PMID- 21854344
TI  - Effect of resistance training regimens on treadmill running and neuromuscular
      performance in recreational endurance runners.
AB  - The purpose of this study was to assess the effects of heavy resistance,
      explosive resistance, and muscle endurance training on neuromuscular, endurance,
      and high-intensity running performance in recreational endurance runners. Twenty
      seven male runners were divided into one of three groups: heavy resistance,
      explosive resistance or muscle endurance training. After 6 weeks of preparatory
      training, the groups underwent an 8-week resistance training programme as a
      supplement to endurance training. Before and after the 8-week training period,
      maximal strength (one-repetition maximum), electromyographic activity of the leg
      extensors, countermovement jump height, maximal speed in the maximal anaerobic
      running test, maximal endurance performance, maximal oxygen uptake ([V.]O(2max)),
      and running economy were assessed. Maximal strength improved in the heavy (P =
      0.034, effect size ES = 0.38) and explosive resistance training groups (P =
      0.003, ES = 0.67) with increases in leg muscle activation (heavy: P = 0.032, ES =
      0.38; explosive: P = 0.002, ES = 0.77). Only the heavy resistance training group
      improved maximal running speed in the maximal anaerobic running test (P = 0.012,
      ES = 0.52) and jump height (P = 0.006, ES = 0.59). Maximal endurance running
      performance was improved in all groups (heavy: P = 0.005, ES = 0.56; explosive: P
      = 0.034, ES = 0.39; muscle endurance: P = 0.001, ES = 0.94), with small though
      not statistically significant improvements in [V.]O(2max) (heavy: ES = 0.08;
      explosive: ES = 0.29; muscle endurance: ES = 0.65) and running economy (ES in all
      groups < 0.08). All three modes of strength training used concurrently with
      endurance training were effective in improving treadmill running endurance
      performance. However, both heavy and explosive strength training were beneficial
      in improving neuromuscular characteristics, and heavy resistance training in
      particular contributed to improvements in high-intensity running characteristics.
      Thus, endurance runners should include heavy resistance training in their
      training programmes to enhance endurance performance, such as improving sprinting
      ability at the end of a race.

PMID- 21854345
TI  - Inhaled fluticasone causes iatrogenic cushing's syndrome in patients treated with
      Ritonavir.
AB  - INTRODUCTION: Ritonavir, a protease inhibitor (PI), is commonly used in the
      treatment of HIV-1 infection. It is a potent inhibitor of the hepatic cytochrome
      P450 superfamily. Therefore, its usage with other PI medications leads to
      significant increases in the levels of the latter PI, which allows a reduction in
      pill burden. Intranasal and inhaled corticosteroids are widely used for the
      treatment of allergic rhinitis and asthma. Inhaled steroids do not usually lead
      to systemic adverse events, since their plasma concentrations are quite low due
      to extensive first-pass metabolism and clearance by CYP3A4. However, the
      coadministration of Ritonavir with inhaled (or intranasal) corticosteroids may
      result in an increase in the plasma corticosteroid levels due to the potent
      CYP3A4 inhibition by Ritonavir. This may cause Cushing's syndrome (laboratory and
      clinical) with adrenal suppression. METHODS: Plasma cortisol and urinary-free
      cortisol levels were determined using immunoassays. In the Synacthen test, plasma
      cortisol levels were measured at time 0 as well as at times 60, 120, and 150
      minutes following an intramuscular injection of 0.25 mg Synacthen. RESULTS: We
      present here three HIV-1 female patients aged 12, 55 and 65 years who developed
      iatrogenic Cushing's syndrome with adrenal suppression following the
      coadministration of Ritonavir and inhaled Fluticasone, both at the standard
      recommended doses. CONCLUSIONS: The coadministration of Ritonavir and Fluticasone
      at the recommended doses caused, in our three patients, iatrogenic Cushing's
      syndrome with adrenal suppression. We suggest that this adverse event is
      underdiagnosed and high clinical suspicion is needed for early diagnosis and
      prenention of Addisonian crises. Thus, Fluticasone treatment should be avoided in
      patients who are treated with Ritonavir. Alternative therapeutic options for
      asthma control such as oral Montelukast or bronchodilators alone should be
      considered.

PMID- 21854346
TI  - Gamma irradiation as a useful tool for the isolation of astaxanthin-overproducing
      mutant strains of Phaffia rhodozyma.
AB  - Astaxanthin is a carotenoid pigment responsible for the red color of the flesh of
      many marine animals. There is an increasing interest in the use of astaxanthin in
      aquaculture, chemical, pharmaceutical, and alimentary industries. Phaffia
      rhodozyma has been identified as the best biological source of astaxanthin.
      Mutagenesis was carried out using different doses of gamma irradiation (1.0, 2.0,
      3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, and 7.0 kGy), and 10 mutant colonies (Gam1
      Gam10) were obtained. Highly pigmented mutant strains produced astaxanthin at
      approximately 15 887.5 ug/L dry mass of yeast, whereas the parental strain
      produced it at 1061.64 ug/g dry mass of yeast. In the thin-layer chromatography
      analysis, P. rhodozyma JH-82 and Gam1 mutant strain produced the same retention
      factor (R(f)) values, but Gam1 showed a higher astaxanthin content than JH-82.

PMID- 21854347
TI  - Roles of BDNF in spinal neuroplasticity in cats subjected to partial dorsal
      ganglionectomy.
AB  - This study investigated the role of brain-derived neurotrophic factor (BDNF) in
      neuroplasticity in cats subjected to the removal of dorsal root ganglia (DRG).
      Following partial ganglionectomy, the number of BDNF-positive varicosities from
      spared L6 DRG decreased significantly. This reduction was observed at 3 days post
      operation (dpo) in spinal lamina II of L3 and L5. Whereas the percentages of
      positive neurons for BDNF and its mRNA in spared L6 DRG at 10 dpo were
      significantly increased, and accumulated BDNF was seen on the DRG side of the
      ligated axons. Importantly, BDNF antibody neutralization in vivo results in a
      significant reduction in the number of varicosities in spinal lamina II,
      evidenced by BDNF and calcitonin gene-related peptide immunohistochemical
      staining. These findings suggested that peripheral-derived BDNF could play a
      critical role in spinal neuroplasticity in cats subjected to partial
      ganglionectomy. This may underlie the basis of molecular therapy depending on
      gene drug-like BDNF release.

PMID- 21854348
TI  - Secular change in height and weight of indigenous school children in Oaxaca,
      Mexico, between the 1970s and 2007.
AB  - BACKGROUND: Information on secular change in indigenous children in Oaxaca,
      southern Mexico, is limited. AIM: To evaluate secular change in heights and
      weights of indigenous school children 6-14 years in four regions of the state of
      Oaxaca between the 1970s and 2007. SUBJECTS AND METHODS: Heights and weights of
      2897 (1419 boys, 1478 girls) and 4305 (2368 boys, 1937 girls) school children 6
      14 years of age were measured in the 1970s (1971-1978) and 2007, respectively.
      The sample was from 18 communities in the 1970s and from 58 communities in 2007
      in four regions of Oaxaca. Sex-specific MANCOVA, with age of the child and
      altitude of each community as covariates, was used to compare size attained in
      the 1970s and 2007 in two age groups: 6-9 years and 10-14 years. RESULTS:
      Indigenous Oaxaca school children are taller and heavier in 2007 than the 1970s.
      Secular gains are larger in youth of 10-14 years than in children of 6-9 years,
      while sex differences are small. CONCLUSION: Improved growth status between the
      1970s and 2007 presumably reflects better health and nutritional conditions in
      indigenous communities of Oaxaca. Mean heights in 2007, however, only approximate
      5(th) percentiles of the US reference.

PMID- 21854349
TI  - Emotional complexity and emotional well-being in older adults: risks of high
      neuroticism.
AB  - Older and midlife adults tend to report greater emotional complexity and greater
      emotional well-being than younger adults but there is variability in these
      factors across the lifespan. This study determined how the personality trait of
      neuroticism at baseline predicts emotional complexity and emotional well-being 10
      years later; a goal was to determine if neuroticism is a stronger predictor of
      these emotion outcomes with increasing age in adulthood. Data were obtained from
      two waves of the MIDUS projects (N = 1503; aged 34-84). Greater neuroticism
      predicted less emotional complexity as indicated by associations between positive
      and negative affect, particularly for older participants. Neuroticism predicted
      lower emotional well-being and this association was stronger for older and
      midlife than for younger adults. Overall, high neuroticism may be a greater
      liability for poor emotion outcomes for older and perhaps for midlife adults than
      for younger persons. Clinical and theoretical implications of this conclusion are
      discussed.

PMID- 21854350
TI  - Participant satisfaction with group and individual components of Adolescent
      Impact: a secondary prevention intervention for HIV-positive youth.
AB  - Adolescent Impact, a developmentally targeted behavioral intervention aimed at
      decreasing risk behaviors and promoting health care adherence, was delivered to
      83 HIV-infected youth, aged 13-21 years, receiving care in five urban HIV
      centers. Participants completed a patient satisfaction survey following the 12
      part intervention consisting of seven groups and five individual sessions. A
      feedback questionnaire was also completed during each group session to gain more
      insight on participant experiences. Several indicators suggested high levels of
      satisfaction. First, overall attendance was relatively high. Second, participants
      rated their subjective experience and group content favorably. No differences in
      satisfaction ratings emerged between perinatally infected adolescents and those
      who acquired HIV through risk behaviors. However, differences emerged regarding
      perceived intervention utility and content-specific preferences. Findings suggest
      that Adolescent Impact participants were satisfied with the intervention and that
      a heterogeneous group of HIV-infected youth could be advantageously integrated
      into the same secondary prevention program.

PMID- 21854351
TI  - Circumcision preference among women and uncircumcised men prior to scale-up of
      male circumcision for HIV prevention in Kisumu, Kenya.
AB  - Following the endorsement by the World Health Organization (WHO) and the Joint
      United Nations Programme on HIV/AIDS (UNAIDS) of male circumcision as an
      additional strategy to HIV prevention, initiatives to introduce safe, voluntary
      medical male circumcision (VMMC) services commenced in 2008 in several sub
      Saharan African communities. Information regarding perceptions of circumcision as
      a method of HIV prevention, however, is largely limited to data collected before
      this important endorsement and the associated increase in the availability of
      VMMC services. To address this, we completed a community-based survey of male
      circumcision (MC) perceptions in the major non-circumcising community in Kenya,
      which is the current focus of VMMC programs in the country. Data was collected
      between November 2008 and April 2009, immediately before VMMC program scale-up
      commenced. Here we present results limited to women (n = 1088) and uncircumcised
      males (n = 460) to provide insight into factors contributing to the acceptability
      and preference for MC in those targeted by VMMC programs. Separate multivariable
      models examining preference for circumcision were defined for married men,
      unmarried men, and women. Belief in the protective effect of circumcision on HIV
      risk was strongly associated with preference for MC in all models. Other
      important factors included education, perceived improvement in sexual pleasure,
      and perceptions of impact on condom utilization. Identified barriers to
      circumcision were the belief that circumcision was not part of the local culture,
      the perception of a long healing period following the procedure, the lack of a
      specific impetus to seek out services, and the general fear of pain associated
      with becoming circumcised. A minority of participants expressed beliefs
      suggesting that behavioral risk compensation with increased MC prevalence and
      awareness is a possibility. This work describes the early impact of a large-scale
      VMMC program on beliefs and behaviors regarding MC and HIV risk. It is hoped that
      our findings may offer guidance into anticipating potential impacts that similar
      programs may observe in populations throughout Eastern Africa.

PMID- 21854352
TI  - Gall stone ileus with acute kidney injury--a case report.
AB  - Gall stone ileus is a rare serious complication of cholelithiasis. We report a
      case of cholecystoduodenal fistula presenting as gall stone ileus with acute
      kidney injury which was managed successfully.

PMID- 21854353
TI  - Impact of nitric oxide synthase Glu298Asp polymorphism on the development of end
      stage renal disease in type 2 diabetic Egyptian patients.
AB  - BACKGROUND: Nitric oxide is an important regulator of renal hemodynamics. This
      study aimed to investigate the role of endothelial nitric oxide synthase (eNOS)
      gene polymorphism in type 2 diabetic patients with end-stage renal disease (ESRD)
      and to elucidate any alteration of nitric oxide synthase (NOS) activity caused by
      this polymorphism. METHODS: The study included 80 patients with type 2 diabetes
      of >10 years duration (40 with diabetes-derived ESRD, 40 without nephropathy) and
      20 healthy controls. Plasma nitrate/nitrite level, and serum NOS activity were
      measured and eNOS Glu298Asp genotypes were determined. RESULTS: The frequency of
      Glu/Glu (GG) genotype in diabetics with ESRD was lower than controls. However,
      the frequency of Asp/Asp (TT) genotype was increased in diabetics with ESRD as
      compared to those without nephropathy and controls. Diabetics with ESRD had
      significantly lower nitrate/nitrite level and NOS activity than those without
      nephropathy. Diabetic patients with TT genotype are at a significant risk for
      ESRD. Moreover, subjects carrying TT genotype had lower nitrate/nitrite level and
      NOS activity than those carrying GG genotype. In diabetics with ESRD, creatinine
      clearance was positively correlated with both nitrate/nitrite level and NOS
      activity. CONCLUSIONS: These results imply that TT genotype of eNOS may be
      associated with an increased risk of ESRD in Egyptian type 2 diabetics. It could
      represent a useful genetic marker to identify diabetics at high risk for the
      development of ESRD. However, larger future prospective studies are required to
      confirm the role of eNOS gene polymorphism in the progression of diabetic
      nephropathy to ESRD.

PMID- 21854354
TI  - Evaluation of LC-high-resolution FT-Orbitrap MS for the quantification of
      selected mycotoxins and the simultaneous screening of fungal metabolites in food.
AB  - A liquid chromatography-high-resolution mass spectrometry-based method is
      reported for the quantification of 20 selected mycotoxins and the simultaneous
      screening for 200 fungal metabolites in food. For regulated mycotoxins, such as
      aflatoxins, fumonisins, ochratoxin A, zearalenone and trichothecenes, the
      evaluation of the method performance characteristics, such as precision,
      trueness, limit of detection and matrix effects, has been exemplified for the
      matrix maize. In the case of the limit of detection, an alternative evaluation
      approach for high-resolution FT-Orbitrap data is proposed. Measurements of the
      signal-to-noise ratios obtained from 'full-profile mode' data led to detection
      limits between 8 and 160 ng g(-1). Eight naturally contaminated wheat- and maize
      based matrix test materials, originating from interlaboratory comparison studies,
      were used to confirm the trueness of the method for deoxynivalenol, zearalenone,
      fumonisin B(1) and B(2), HT-2, and T-2 toxin. In addition to accurate
      quantification of the most relevant mycotoxins, the full-scan chromatograms were
      used to investigate the potential of the FT-Orbitrap to screen simultaneously for
      a large number of fungal metabolites. First, a list of 200 metabolites,
      potentially being present in food samples, was established. Next, specific
      detection and identification criteria were defined, which are based on accurate
      mass, peak intensity and isotopologue ratio. The application of these criteria to
      the suspected metabolites from the list resulted in the putative identification
      of 13 fungal metabolites in addition to the target toxins.

PMID- 21854355
TI  - Recent applications of DNA sequencing technologies in food, nutrition and
      agriculture.
AB  - Next-generation DNA sequencing technologies are able to produce millions of short
      sequence reads in a highthroughput, cost-effective fashion. The emergence of
      these technologies has not only facilitated genome sequencing but also changed
      the landscape of life sciences. This review surveys their recent applications in
      food, nutrition and agriculture ranging from whole-genome sequencing and
      resequencing, RNA-seq and ChIP-seq, structural, functional and comparative
      genomics to metagenomics and epigenetics. We already began to witness broad
      impacts of these DNA sequencing technologies for solving the complex biological
      problems in food, nutrition and agriculture. In this article, recent patent-based
      information is also included.

PMID- 21854356
TI  - Expanding targets for a metabolic therapy of cancer: L-asparaginase.
AB  - The antitumour enzyme L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1,
      ASNase), which catalyses the deamidation of L-asparagine (Asn) to L-aspartic acid
      and ammonia, has been used for many years in the treatment of acute lymphoblastic
      leukaemia. Also NK tumours, subtypes of myeloid leukaemias and T-cell lymphomas
      respond to ASNase, and ovarian carcinomas and other solid tumours have been
      proposed as additional targets for ASNase, with a potential role for its
      glutaminase activity. The increasing attention devoted to the antitumour activity
      of ASNase prompted us to analyse recent patents specifically concerning this
      enzyme. Here, we first give an overview of metabolic pathways affected by Asn and
      Gln depletion and, hence, potential targets of ASNase. We then discuss recent
      published patents concerning ASNases. In particular, we pay attention to novel
      ASNases, such as the recently characterised ASNase produced by Helicobacter
      pylori, and those presenting amino acid substitutions aimed at improving
      enzymatic activity of the classical Escherichia coli enzyme. We detail
      modifications, such as natural glycosylation or synthetic conjugation with other
      molecules, for therapeutic purposes. Finally, we analyse patents concerning
      biotechnological protocols and strategies applied to production of ASNase as well
      as to its administration and delivery in organisms.

PMID- 21854357
TI  - Current and future medical therapy, and the molecular features of adrenocortical
      cancer.
AB  - Adrenocortical carcinoma (ACC) is a rare neoplasm with very poor prognosis
      despite the recent development of aggressive antitumor therapies. The cause of
      adrenal cancer remains elusive, but some molecular mechanisms could be
      responsible for its development. Target-specific therapies have been developed
      for a number of human malignancies and have resulted in therapeutic benefits in
      some cancer patients. However, these therapies are only effective in cases in
      which the corresponding targets are expressed in tumor tissues. Molecular
      analysis has had a significant impact on the understanding of the pathogenetic
      mechanism of ACC development and the evaluation of prognostic and predictive
      markers, among which alterations of the IGF system, the Wnt pathway, p53 and
      molecules involved in cancer cell invasion properties and angiogenesis seem to be
      very promising. These molecular markers may not just play a role in the biology
      of these tumors and have prognostic implications, but can also be used as
      potential targets for treatment. The aim of this review is to summarize the
      genetic and molecular events implied in the pathogenesis of ACC and to highlight
      challenges to the development of anticancer agents in recent patents.

PMID- 21854358
TI  - Antineoplastic action of growth hormone-releasing hormone (GHRH) antagonists.
AB  - Some of the antagonists of growth hormone-releasing hormone (GHRH) are able to
      inhibit the growth of various experimental human cancers. The antitumor effects
      of first antagonists seemed to be dependent mainly on the disruption of pituitary
      secretion of growth hormone (GH), followed by the reduction in the levels of
      circulating insulin-like growth factor (IGF)-1, an important growth factor for
      cancer cells. It seems obvious, that growth hormone deficiency (GHD) induced by
      GHRH antagonists with all its complications, could limit the beneficial effects
      of GHRH antagonists therapy, and decrease patients' quality of life. The
      discovery of local autocrine/paracrine production of GHRH and other related
      growth factors in many tumoral tissues, in combination with the wide expression
      of GHRH receptors on cancer cells, directed the research to the synthesis of more
      potent GHRH antagonists. These compounds exert strong inhibitory effects directly
      on tumor growth, with scarce endocrine action. The receptor-mediated mechanisms
      comprise complex and still not completely understood effects on intracellular
      signaling pathways that are strictly related to human tumorigenesis. This review
      summarizes recent patents and latest observations on the antineoplastic role of
      GHRH antagonists in human tumors with emphasis on potential therapeutic
      applications in clinical oncology.

PMID- 21854359
TI  - Insights into angiogenesis in non-small cell lung cancer: molecular mechanisms,
      polymorphic genes, and targeted therapies.
AB  - Lung cancer is a highly prevalent disease worldwide. Currently, there are more
      than 150 million patients with lung cancer in the world, with more than 1 million
      new cases diagnosed per year. Tumoral angiogenesis is an important hallmark of
      this disease, but despite being extensively studied, the complete angiogenic
      mechanisms are not fully elucidated. Recent studies have reported a correlation
      between pharmacological inhibition of these angiogenic mechanisms and improvement
      of overall survival in lung cancer patients, mainly for those in advanced stages.
      The family of vascular endothelial growth factor (VEGF) proteins has critical
      roles in tumoral angiogenesis. An interaction between VEGF-A and VEGF receptor 2
      (VEGFR-2) is the main pathway of activation and maintenance of angiogenesis. In
      tumors, this process is intimately correlative with progression and metastasis.
      Some studies suggested that serum levels of VEGF are higher in patients with lung
      cancer, especially in some types of non-small cell lung cancer (NSCLC). Other
      studies revealed that genetic polymorphisms of VEGF correlate with
      susceptibility, prognosis, and therapeutic response of some patients with NSCLC.
      This paper aims to review the impact of angiogenesis, especially on VEGF
      pathways, in NSCLC, and highlights the relevance of known and new patents
      disclosed of anti-angiogenic therapies in these patients.

PMID- 21854360
TI  - Recent patents on anti-telomerase cancer therapy.
AB  - Telomerase, a specialised RNA-directed DNA polymerase extends and stabilises the
      telomeres at the ends of the eukaryotic chromosomes. The progressive loss of
      telomeres results in limited number of cell divisions and has been linked to the
      mechanism of human cellular ageing. Tumour cells marked by indefinite
      proliferation have stable telomere length maintained by telomerase. The
      differential expression of the telomerase enzyme in normal and cancer cells have
      led to the evolution of tumour specific anti-telomerase approaches which inhibit
      the telomerase enzyme activity so as to destabilise and shorten the telomeres
      leading to senescence in cancer cells. In the current review, we have selected
      nine tumour specific anti-telomerase approaches based on their mechanism of
      action or the target components of the human telomerase enzyme: Antisense
      oligonucleotides, hammerhead ribozymes, dominant negative hTERT, reverse
      transcriptase inhibitors, immunotherapy, G-quadruplex stabilisers, gene therapy,
      small molecule inhibitors and RNA interference. Recent research developments for
      each of the anti-telomerase approaches with the detailed analysis of specific
      granted patents from the perspective of different claims and downstream
      applications have been provided. A comprehensive list of patents for the
      different anti-telomerase approaches which includes information regarding the
      authors and institutional ownership along with the year of issue of the patent
      has also been provided.

PMID- 21854361
TI  - An updated patent therapeutic agents targeting MMPs.
AB  - The traditional consensus that matrix metalloproteinases (MMPs) has correlation
      with various pathological and physiological processes led to the exploitation of
      a vast number of natural or synthetic broad-spectrum MMP inhibitors (MMPIs) for
      the prophylaxis or treatment of various MMP-related disorders, such as
      autoimmune, inflammatory, cardiovascular, neurodegenerative, respiratory
      diseases, and malignant cancer as well. Yet the unsatisfactory preclinical and/or
      clinical results motivated further investigation of the physiological roles of
      certain MMP subtypes. Despite the intricate and complicated MMP functions in
      normal physiology and disease pathology, the effort of designing specific
      inhibitors that can selectively target certain MMP family members for
      individualized therapy is ongoing and remains an arduous task. Success will rely
      on continued insight into the biological roles of these multifaced proteases. In
      our previous effort, we summarized various MMPIs that have entered preclinical or
      clinical trials as well as the patents in regard to MMPIs (Recent Pat Anticancer
      Drug Discov. 2010; 5(2): 109-41). In our on-going review, to illustrate the major
      challenges in MMP validation as druggable targets, we highlighted the
      physiological and pathological roles of representative MMPs, with an emphasis on
      description of the newly emerging MMPI-based patents, in particular, the
      inhibitors containing sulfonamide or sulfone motif. By analyzing the structural
      characteristics and selectivity profiles of these supplementary inhibitors, we
      hereby described their pharmaceutical application, and also expanded the
      strategies for potent MMPI design.

PMID- 21854362
TI  - Application of hyperthermia for cancer treatment: recent patents review.
AB  - Cancer is one of the main causes of death in the world and its incidence
      increases every day. Current treatments are insufficient and present many
      breaches. Hyperthermia is an old concept and since early it was established as a
      cancer treatment option, mainly in superficial cancers. More recently the concept
      of intracellular hyperthermia emerged wherein magnetic particles are concentrated
      at the tumor site and remotely heated using an applied magnetic field to achieve
      hyperthermic temperatures (42-45 degrees C). Many patents have been registered in
      this area since the year 2000. This review presents the most relevant
      information, organizing them according to the hyperthermic method used: 1)
      external Radio-Frequency devices; 2) hyperthermic perfusion; 3) frequency
      enhancers; 4) apply heating to the target site using a catheter; 5) injection of
      magnetic and ferroelectric particles; 6) injection of magnetic nanoparticles that
      may carry a pharmacological active drug. The use of magnetic nanoparticles is a
      very promising treatment approach since it may be used for diagnostic and
      treatment. An ideal magnetic nanoparticle would be able to detect and diagnose
      the tumor, carry a pharmacological active drug to be delivered in the tumor site,
      apply hyperthermia through an external magnetic field and allow treatment
      monitoring by magnetic resonance imaging.

PMID- 21854363
TI  - Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic
      applications.
AB  - UDCA (ursodeoxycholic acid) is the therapeutic agent most widely used for the
      treatment of cholestatic hepatopathies. Its use has expanded to other kinds of
      hepatic diseases, and even to extrahepatic ones. Such versatility is the result
      of its multiple mechanisms of action. UDCA stabilizes plasma membranes against
      cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts
      apoptosis by preventing the formation of mitochondrial pores, membrane
      recruitment of death receptors and endoplasmic-reticulum stress. In addition,
      UDCA induces changes in the expression of metabolizing enzymes and transporters
      that reduce bile acid cytotoxicity and improve renal excretion. Its capability to
      positively modulate ductular bile flow helps to preserve the integrity of bile
      ducts. UDCA also prevents the endocytic internalization of canalicular
      transporters, a common feature in cholestasis. Finally, UDCA has immunomodulatory
      properties that limit the exacerbated immunological response occurring in
      autoimmune cholestatic diseases by counteracting the overexpression of MHC
      antigens and perhaps by limiting the production of cytokines by immunocompetent
      cells. Owing to this multi-functionality, it is difficult to envisage a
      substitute for UDCA that combines as many hepatoprotective effects with such
      efficacy. We predict a long-lasting use of UDCA as the therapeutic agent of
      choice in cholestasis.

PMID- 21854364
TI  - Robot-assisted laparoscopic hysterectomy in obese and morbidly obese women:
      surgical technique and comparison with open surgery.
AB  - OBJECTIVE: Comparison of surgical results on obese patients undergoing
      hysterectomy by robot-assisted laparoscopy or laparotomy. SETTING: University
      hospital. METHODS: All women (n=114) with a BMI >=30 kg/m(2) who underwent a
      simple hysterectomy as the main surgical procedure between November 2005 and
      November 2009 were identified. Robot-assisted procedures (n=50) were separated
      into an early (learning phase) and a late (consolidated phase) group; open
      hysterectomy was considered an established method. Relevant data was retrieved
      from prospective protocols (robot) or from computerized patient charts
      (laparotomy) until 12 months after surgery. Complications leading to prolonged
      hospital stay, readmission/reoperation, intravenous antibiotic treatment or blood
      transfusion were considered significant. The surgical technique used for morbidly
      obese patients is described. RESULTS: Women in the late robot group (n=25) had
      shorter inpatient time (1.6 compared to 3.8 days, p<0.0001), less bleeding (100
      compared to 300 mL, p<0.0001) and fewer complications (2/25 compared to 23/64,
      p=0.006) than women with open surgery (n=64) but a longer operating time (136
      compared to 110 minutes, p=0.0004). For women with a BMI >=35 kg/m(2) , surgical
      time in the late robot group and the laparotomy group was equal (136 compared to
      128 minutes, p=0.31). CONCLUSIONS: Robot-assisted laparoscopic hysterectomy in a
      consolidated phase in obese women is associated with shorter hospital stay, less
      bleeding and fewer complications compared to laparotomy but, apart from women
      with BMI >=35, a longer operative time.

PMID- 21854365
TI  - Does conventional or single port laparoscopically assisted vaginal hysterectomy
      affect female sexual function?
AB  - OBJECTIVE: To investigate the effects of conventional and single port
      laparoscopically assisted vaginal hysterectomy (LAVH) on sexual function in
      premenopausal women. DESIGN: A prospective case-control study. SETTING:
      University teaching hospital. Population. A total of 95 premenopausal women
      having LAVH from January 2009 to December 2009. METHODS: Comparison of 47
      premenopausal women who had single port LAVH using trans-umbilical GelPort access
      (SP-LAVH group) and 48 premenopausal women who had conventional multiport LAVH
      (conventional LAVH group). MAIN OUTCOME MEASURES: Evaluation of sexual function
      was done prior to and six months after surgery using a validated tool, the female
      sexual function index (FSFI). RESULTS: In terms of women's demographic
      characteristics and operative results, there was no significant difference
      between the two study groups, or between pre- and postoperative individual domain
      scores or total female sexual function index in women who underwent either
      conventional or single port LAVH. CONCLUSIONS: Neither conventional nor single
      port LAVH affects sexual function in premenopausal women. Women can be counseled
      that this type of surgery is unlikely to alter sexual function.

PMID- 21854367
TI  - Recent developments in the clinical use of the levonorgestrel-releasing
      intrauterine system.
AB  - This overview focuses on recent developments in the clinical use of the
      levonorgestrel- releasing intrauterine system (LNG-IUS) on established
      indications. Recent studies confirm that the LNG-IUS is safe and equally
      effective for all age groups of women. All available studies showed that
      intrauterine contraception is more effective when compared to non-intrauterine
      contraceptive methods to prevent repeat abortions. Furthermore, insertion in
      young nulliparous women is acceptable in the majority of women and associated
      with high continuation rates. The effectivity of LNG-IUS appears to be similar in
      women with chronic medical conditions, including HIV infection or coagulation
      disorders, and healthy women. More and most importantly, it has no adverse effect
      on the underlying condition. We also discuss effects of LNG-IUS on bone mineral
      density, vaginal flora, cardiovascular risk factors and breast cancer. In
      treatment of heavy menstrual bleeding, the LNG-IUS appears to be one of the most
      effective and cost-effective methods.

PMID- 21854366
TI  - Maternal weight gain in twin-twin transfusion syndrome.
AB  - OBJECTIVE: To examine the association between maternal weight gain and twin-twin
      transfusion syndrome (TTTS). DESIGN: Retrospective observational study in two
      tertiary care centers. POPULATION: All 124 women with monochorionic diamniotic
      twin pregnancies who gave birth at >= 16 gestational weeks between 2002 and 2010.
      METHODS: Analysis of chronological relation between maternal weight gain per week
      (weekly gain) and the diagnosis of TTTS. MAIN OUTCOME MEASURE: Sonographic
      diagnosis of TTTS. RESULTS: A weekly weight gain >= 1.4 kg occurred in 45 women,
      preceded the diagnosis of TTTS in 22 (78.6%) of the 28 women with TTTS, and was
      associated with TTTS [women with one weekly weight gain >= 1.4 kg vs. women with
      no weekly weight gains >=1.4 kg who were diagnosed as having TTTS: 48.9% (22/45)
      vs. 7.6% (6/79); RR, 6.44; 95%CI, 2.82-14.69]. At given gestational weeks between
      16 and 27, the mean (+/- SD) prospective risk of the development of TTTS within
      three weeks was 52.0 +/- 33.8% among women who showed a weekly weight gain >= 1.4
      kg for the first time, whereas the risk of the development of TTTS within one
      week was 1.6 +/- 1.7% among women who never showed a weekly weight gain >= 1.4
      kg. CONCLUSIONS: Excessive maternal weight gain >= 1.4 kg/week is likely to occur
      during the development of TTTS.

PMID- 21854368
TI  - Left upper quadrant approach in gynecologic laparoscopic surgery.
AB  - OBJECTIVE: To review the use of the left upper quadrant approach in benign
      gynecologic laparoscopic surgery over a nine-year period. DESIGN: Retrospective
      review. Setting. University-affiliated hospital. POPULATION: Women who underwent
      laparoscopic gynecologic surgery the upper quadrant approach between January 2002
      and December 2010. METHODS: Medical records were reviewed. MAIN OUTCOME MEASURES:
      Demographic data, past surgical histories, indications for surgery and the use of
      the left upper quadrant approach, intraoperative findings, diagnosis and any
      complications. RESULTS: 143 patients were identified, accounting for 4.9% of all
      gynecologic laparoscopic surgery. The indications for using the left upper
      quadrant approach were: previous open abdominal surgery (113, 79.0%), surgery in
      the second trimester of pregnancy (16, 11.1%), presence of large pelvic mass (9,
      6.2%), previous transverse rectus abdominis myocutaneous flap for breast
      reconstruction (3, 2.0%), previous periumbilical hernia repair (1, 0.6%) and
      previous laparoscopic umbilical wound dehiscence (1, 0.6%). In women with
      previous abdominal surgery, the overall incidence of adhesions between omentum
      and/or bowel to the anterior abdominal wall in the umbilical region was 58.4%.
      Twelve (8.3%) patients required conversion to laparotomy. One patient had
      subcutaneous surgical emphysema over the left upper quadrant entry site.
      CONCLUSIONS: The left upper quadrant approach is an effective, safe and easy
      technique for peritoneal cavity access in women undergoing laparoscopic
      gynecologic surgery and should be considered in women with risk factors of
      periumbilical adhesions and in the presence of a large pelvic mass.

PMID- 21854369
TI  - How understanding the neurobiology of complex post-traumatic stress disorder can
      inform clinical practice: a social cognitive and affective neuroscience approach.
AB  - OBJECTIVE: In this review, we examine the relevance of the social cognitive and
      affective neuroscience (SCAN) paradigm for an understanding of the psychology and
      neurobiology of complex post-traumatic stress disorder (PTSD) and its effective
      treatment. METHOD: The relevant literature pertaining to SCAN and PTSD was
      reviewed. RESULTS: We suggest that SCAN offers a novel theoretical paradigm for
      understanding psychological trauma and its numerous clinical outcomes, most
      notably problems in emotional/self-awareness, emotion regulation, social
      emotional processing and self-referential processing. A core set of brain regions
      appear to mediate these collective psychological functions, most notably the
      cortical midline structures, the amygdala, the insula, posterior parietal cortex
      and temporal poles, suggesting that problems in one area (e.g. emotional
      awareness) may relate to difficulties in another (e.g. self-referential
      processing). We further propose, drawing on clinical research, that the
      experiences of individuals with PTSD related to chronic trauma often reflect
      impairments in multiple social cognitive and affective functions. CONCLUSION: It
      is important that the assessment and treatment of individuals with complex PTSD
      not only addresses traumatic memories but also takes a SCAN-informed approach
      that focuses on the underlying deficits in emotional/self-awareness, emotion
      regulation, social emotional processing and self-referential processing.

PMID- 21854370
TI  - Laryngoscopy: time to shed fresh light?

PMID- 21854373
TI  - Diagnosis and management of fibromuscular dysplasia: an expert consensus.

PMID- 21854372
TI  - Validation of the rat model of cryptogenic infantile spasms.
AB  - PURPOSE: To determine whether a new model of cryptogenic infantile spasms
      consisting of prenatal priming with betamethasone and postnatal trigger of spasms
      by N-methyl-D-aspartate (NMDA) responds to chronic adrenocorticotropic hormone
      (ACTH) treatment, and has electroencephalography (EEG) signature, efficacy of
      treatments, and behavioral impairments similar to those in human infantile
      spasms. METHODS: Rats prenatally primed with betamethasone on gestational day 15
      were used. Spasms were triggered with NMDA between postnatal days (P) 10 and 15
      in a single session or in multiple sessions in one subject. The expression of
      spasms was compared to prenatally saline-injected controls. Effects of relevant
      treatments (ACTH, vigabatrin, methylprednisolone, rapamycin) were determined in
      betamethasone-primed rats. In the rats after spasms, behavioral evaluation was
      performed in the open field and elevated plus maze on P20-22. KEY FINDINGS: NMDA
      at P10-15 (the rat "infant" period) triggers the spasms significantly earlier and
      in greater numbers in the prenatal betamethasone-exposed brain compared to
      controls. Similar to human condition, the spasms occur in clusters. Repeated
      trigger of spasms is associated with ictal EEG electrodecrements and interictal
      large-amplitude waves, a possible rat variant of hypsarrhythmia. Chronic ACTH
      treatment in a randomized experiment, and chronic pretreatment with
      methylprednisolone significantly suppress the number of spasms similar to the
      human condition. Pretreatment with vigabatrin, but not rapamycin, suppressed the
      spasms. Significant behavioral changes occurred following multiple bouts of
      spasms. SIGNIFICANCE: The model of infantile spasms has remarkable similarities
      with the human condition in semiology, EEG, pharmacologic response, and long-term
      outcome. Therefore, the model can be used to search for novel and more effective
      treatments for infantile spasms.

PMID- 21854374
TI  - A modeling framework for the design of collector wells.
AB  - We present results of a design study performed for the Saylorville Wellfield in
      Iowa, which is owned and operated by the Des Moines Water Works. The purpose of
      this study was to estimate wellfield capacity and provide a preliminary design
      for two radial collector wells to be constructed in the outwash aquifer along the
      Des Moines River near Saylorville, Iowa. After a field investigation to
      characterize the aquifer, regional two-dimensional and local three-dimensional,
      steady-state groundwater flow modeling was performed to locate and design the
      wells. This modeling was the foundation for design recommendations based on the
      relative performance of 12 collector well designs with varying lateral numbers,
      elevations, screen lengths, and orientations. For each site, alternate designs
      were evaluated based on model estimates of the capacity, the percent of surface
      water captured, and the production per unit length of screen. Many of our results
      are consistent with current design practices based on experience and intuition,
      but our methods allow for a quantitative approach for comparing alternate
      designs. Although the results are site-specific, the framework for evaluating the
      hydraulic design of the Saylorville radial collector wells is broadly applicable
      and could be used at other riverbank filtration sites. In addition, many of the
      conclusions from this design study may apply at other sites where construction of
      radial collector wells is being considered.

PMID- 21854375
TI  - The discovery-dominance trade-off is the exception, rather than the rule.
AB  - 1. Interspecific trade-offs are thought to facilitate coexistence between species
      at small spatial scales. The discovery-dominance trade-off, analogous to a
      competition-colonisation trade-off, is considered an important structuring
      mechanism in ant ecology. A trade-off between species' ability to discover food
      resources and to dominate them may explain how so many species apparently
      dependent on similar resources can coexist. 2. The discovery-dominance trade-off
      is thought to be broken by invasive species in enemy-free space or territorial
      species whose activity is fuelled by domination of carbohydrate resources. It may
      also be mediated by factors such as temperature and habitat structure. 3. We
      investigate the generality and form of the discovery-dominance relationship in an
      experiment using habitats of contrasting complexity across three continents. In
      addition, to assess how widespread the discovery-dominance trade-off is, we
      conducted a systematic review combining all empirical studies (published and from
      our experiment). 4. From our own fieldwork and meta-analyses of available
      studies, we find surprisingly little empirical support for the trade-off, with
      results indicating that mean effect sizes were either not significantly different
      from 0 or significantly positive. The trade-off was only detected in studies with
      parasitoids present. Additionally, experimental data from simple and complex
      habitats within each continent suggest that simple habitats may facilitate both
      food resource discovery and dominance. 5. We conclude that the discovery
      dominance trade-off is the exception, rather than the rule. Instead, these
      abilities were commonly correlated. Real food resources provide many axes along
      which partitioning may occur, and discovery-dominance trade-offs are not a
      prerequisite for coexistence.

PMID- 21854376
TI  - A simulation for exploring the effects of the "trait list" method's subjectivity
      on consistency and accuracy of ancestry estimations.
AB  - The nonmetric "trait list" methodology is widely used for estimating ancestry of
      skeletal remains. However, the effects of the method's embedded subjectivity on
      subsequent accuracy and consistency are largely unknown. We develop a
      mathematical simulation to test whether variation in the application of the
      "trait list" method alters the ancestry estimation for a given case. Our
      simulation explores how variations in (i) trait selection, (ii) number of traits
      employed, and (iii) ancestry choice thresholds affect the ancestry estimation of
      an unidentified skeleton. Using two temporally and geographically diverse
      samples, the simulation demonstrates that trait selection, trait quantity,
      threshold choices, and the exclusion of high-frequency traits had minimal effect
      on estimation of general ancestry. For all data sets and Runs, Accuracy(AS) was
      maintained above 90%. The authors close with a discussion on the logistical
      issues present when choosing traits, and how to avoid ancestry bias.

PMID- 21854377
TI  - Identification of forensically important sarcophagid flies (Diptera:
      Sarcophagidae) in China, based on COI and 16S rDNA gene sequences.
AB  - Insects attracted to cadavers may provide important indications of the postmortem
      interval (PMI). However, use of the flesh flies (Diptera: Sarcophagidae) for PMI
      estimation is limited as the species are often not morphologically distinct,
      especially as immatures. In this study, 23 forensically important flesh flies
      were collected from 13 locations in 10 Chinese provinces. Then, a 278-bp segment
      of the cytochrome oxidase subunits one (COI) gene and a 289-bp segment of the 16S
      rDNA gene of all specimens were successfully sequenced. Phylogenetic analysis of
      the sequenced segments showed that all sarcophagid specimens were properly
      assigned into four species (Boerttcherisca peregrina [Robineau-Desvoidy, 1830],
      Helicophagella melanura [Meigen, 1826], Parasarcophaga albiceps [Meigen, 1826],
      and Parasarcophaga dux [Thompson, 1869]) with relatively strong supporting
      values, thus indicating that the COI and 16S rDNA regions are suitable for
      identification of sarcophagid species. The difference between intraspecific
      threshold and interspecific divergence confirmed the potential of the two regions
      for sarcophagid species identification.

PMID- 21854378
TI  - A comparison of Demirjian's four dental development methods for forensic age
      assessment.
AB  - The aim of this study was to determine the comparative accuracy of Demirjian's
      four dental development methods for forensic age estimation in the Western
      Australian population. A sample comprising 143 individuals aged 4.6 to 14.5 years
      were assessed using Demirjian's four methods for dental development (original 7
      tooth: M(2), M(1), PM(2), PM(1), C, I(2), and I(1); revised 7-tooth: M(2), M(1),
      PM(2), PM(1), C, I(2), and I(1); 4-tooth: M(2), M(1), PM(2), and PM(1); and an
      alternate 4-tooth: M(2), PM(2), PM(1), and I(1)). When comparing all four
      methods, the 4-tooth method overestimated age in both males and females by 0.04
      and 0.25 years, respectively. The original 7-tooth was least accurate for males,
      while the original 7-tooth, the revised 7-tooth, and the alternate 4-tooth were
      unsuitable for females. Therefore, we recommend the 4-tooth method to be used for
      forensic age estimation in Western Australian males and females, as it has the
      lowest overall mean deviation and the highest accuracy.

PMID- 21854379
TI  - To evaluate the utility of smaller sample sizes when assessing dental maturity
      curves for forensic age estimation.
AB  - Dental maturation and chronological age estimation were determined from 144
      healthy Western Australian individuals aged 3.6-14.5 years. The results were
      compared with Farah et al.'s previous study which comprised a larger
      heterogeneous sample of Western Australian individuals (n = 1450).
      Orthopantomograms were analyzed with the application of Demirjian and Goldstein's
      4-tooth method based on eight stages of dental mineralization. Analysis of
      variance revealed no significant differences in dental maturity scores in each
      age group among the males in both studies; similar results were seen in the
      females. Paired t-tests showed no statistical significance overall between
      chronological and estimated ages for the males in our sample (p = 0.181), whereas
      the females showed significant differences (p < 0.001). Our results show that
      smaller samples may be used when assessing dental maturity curves for forensic
      age estimation.

PMID- 21854380
TI  - A study of sexual dimorphism in the femur among North Indians.
AB  - Determination of sex of unknown skeleton remains is the most important step in
      the identification process. Racial and regional differences in the populations
      create and maintain specificity in their dimorphic characteristics. Moreover,
      considering continued secular changes in the population structure, constant
      revision of osteometric standards becomes mandatory. In an effort to establish
      osteometric standards for the femur of contemporary North Indian populations, 122
      adult femora of known sex (M: 94; F: 28) were collected in the Department of
      Forensic Medicine, IMS, BHU, Varanasi. Eight standard parameters were measured
      and analyzed by discriminant function analysis using SPSS 16. The accuracy of sex
      prediction ranged from 70.5% to 83.6% with single variables. In stepwise
      analysis, epicondylar breadth, proximal breadth, and antero-posterior diameter of
      the lateral condyle were found to be the most discriminating variables providing
      an accuracy of 90.2%. The results clearly indicate the importance of the ends of
      femur in the determination of sex.

PMID- 21854381
TI  - Using fire dynamics simulator to reconstruct a hydroelectric power plant fire
      accident.
AB  - The location of the hydroelectric power plant poses a high risk to occupants
      seeking to escape in a fire accident. Calculating the heat release rate of
      transformer oil as 11.5 MW/m(2), the fire at the Taiwan Dajia-River hydroelectric
      power plant was reconstructed using the fire dynamics simulator (FDS). The
      variations at the escape route of the fire hazard factors temperature, radiant
      heat, carbon monoxide, and oxygen were collected during the simulation to verify
      the causes of the serious casualties resulting from the fire. The simulated safe
      escape time when taking temperature changes into account is about 236 sec, 155
      sec for radiant heat changes, 260 sec for carbon monoxide changes, and 235-248
      sec for oxygen changes. These escape times are far less than the actual escape
      time of 302 sec. The simulation thus demonstrated the urgent need to improve
      escape options for people escaping a hydroelectric power plant fire.

PMID- 21854382
TI  - Validation of the Seratec(r) SeraQuantTM for the quantitation of prostate
      specific antigen levels on immunochromatographic membranes.
AB  - Use of immunochromatographic membranes for the detection of prostate-specific
      antigen (PSA) has become commonplace in forensic laboratories. Experiments were
      designed to test the newly developed Seratec((r))  SeraQuantTM for accuracy,
      precision, and consistency in the quantitation of PSA. PSA standards were diluted
      with buffers and run on the instruments. Values obtained were examined for
      accuracy (was the correct value obtained?) and precision (were multiple sample
      values consistent?). To test for variation between instruments, large volumes of
      diluted PSA standard were run repeatedly on six units and the values obtained
      were plotted against the known PSA values to obtain a standard curve for each
      instrument. Fifty membranes having negative or weak positive results were then
      run on the six units, and the adjusted values were recorded and compared. Results
      of these experiments indicate that the instruments are accurate and precise in
      the quantitation of low levels of PSA.

PMID- 21854383
TI  - Efficacy of forensic statement analysis in distinguishing truthful from deceptive
      eyewitness accounts of highly stressful events.
AB  - Laboratory-based detecting deception research suggests that truthful statements
      differ from those of deceptive statements. This nonlaboratory study tested
      whether forensic statement analysis (FSA) methods would distinguish genuine from
      false eyewitness accounts about exposure to a highly stressful event. A total of
      35 military participants were assigned to truthful or deceptive eyewitness
      conditions. Genuine eyewitness reported truthfully about exposure to
      interrogation stress. Deceptive eyewitnesses studied transcripts of genuine
      eyewitnesses for 24 h and falsely claimed they had been interrogated. Cognitive
      Interviews were recorded, transcribed, and assessed by FSA raters blind to the
      status of participants. Genuine accounts contained more unique words, external
      and contextual referents, and a greater total word count than did deceptive
      statements. The type-token ratio was lower in genuine statements. The
      classification accuracy using FSA techniques was 82%. FSA methods may be
      effective in real-world circumstances and have relevance to professionals in law
      enforcement, security, and criminal justice.

PMID- 21854384
TI  - An inconclusive digital audio authenticity examination: a unique case.
AB  - This case report sets forth an authenticity examination of 35 encrypted,
      proprietary-format digital audio files containing recorded telephone
      conversations between two codefendants in a criminal matter. The codefendant who
      recorded the conversations did so on a recording system he developed;
      additionally, he was both a forensic audio authenticity examiner, who had
      published and presented in the field, and was the head of a professional audio
      society's writing group for authenticity standards. The authors conducted the
      examination of the recordings following nine laboratory steps of the peer
      reviewed and published 11-step digital audio authenticity protocol. Based
      considerably on the codefendant's direct involvement with the development of the
      encrypted audio format, his experience in the field of forensic audio
      authenticity analysis, and the ease with which the audio files could be accessed,
      converted, edited in the gap areas, and reconstructed in such a way that the
      processes were undetected, the authors concluded that the recordings could not be
      scientifically authenticated through accepted forensic practices.

PMID- 21854385
TI  - Experimental and casework validation of ambient temperature corrections in
      forensic entomology.
AB  - This paper expands on Archer (J Forensic Sci 49, 2004, 553), examining additional
      factors affecting ambient temperature correction of weather station data in
      forensic entomology. Sixteen hypothetical body discovery sites (BDSs) in Victoria
      and New South Wales (Australia), both in autumn and in summer, were compared to
      test whether the accuracy of correlation was affected by (i) length of
      correlation period; (ii) distance between BDS and weather station; and (iii)
      periodicity of ambient temperature measurements. The accuracy of correlations in
      data sets from real Victorian and NSW forensic entomology cases was also
      examined. Correlations increased weather data accuracy in all experiments, but
      significant differences in accuracy were found only between periodicity
      treatments. We found that a >5 degrees C difference between average values of
      body in situ and correlation period weather station data was predictive of
      correlations that decreased the accuracy of ambient temperatures estimated using
      correlation. Practitioners should inspect their weather data sets for such
      differences.

PMID- 21854386
TI  - Sudden death and Angelman syndrome.
AB  - Angelman syndrome is a condition characterized by developmental delay due to
      abnormalities in the maternally derived chromosome 15q11-q13. Typical features
      include impaired expressive language, an ataxic gait, and seizures. Hyperactivity
      may result in accidental bruises and abrasions, raising issues of possible
      inflicted injury. A fascination with water may predispose to drowning. A 5-year
      old boy with an established diagnosis of Angelman syndrome is reported who died
      of upper airway obstruction due to massively enlarged tonsils complicating
      infectious mononucleosis. Assessment of the severity of underlying illness in
      developmentally delayed children may be difficult due to failure to vocalize
      worsening symptoms and distress. In addition, signs of upper airway narrowing due
      to infection in Angelman syndrome may be masked by the sucking and swallowing
      difficulties that affected individuals may have with drooling and excessive
      chewing and mouthing behavior.

PMID- 21854387
TI  - Context effects and observer bias--implications for forensic odontology.
AB  - Psychologists have long recognized the effects of contextual and extraneous
      information on decision making. Such information renders the subject susceptible
      to both motivational and cognitive bias; yet, it is difficult to assess the
      extent to which these influence forensic odontologists opinions as there have
      been no studies to date on this subject. This article explores the various types
      of contextual effects and biasing influences that potentially impact on the
      analysis of bitemarks in forensic odontology. It appears that the current
      practice of bitemark analysis is rich in sources of potentially biasing
      influences. In addition to the fundamental recognition that some form of bias is
      likely to exist, ways in which these should be minimized include: separation of
      the collection and analysis phases; limiting the amount of contextual information
      available to the odontologist responsible for the analysis; and ensuring that
      evidence that is ambiguous or of poor quality is identified as such prior to
      analysis.

PMID- 21854388
TI  - Sudden and unexpected death from pituitary tumor apoplexy.
AB  - Pituitary tumor apoplexy refers to a clinical syndrome precipitated by the
      expansion of a pituitary adenoma by hemorrhage or infarction. Individuals may
      present with myriad signs, including sudden onset of severe headache, visual
      changes, altered mental status, cranial nerve palsies, and hormonal dysfunction.
      This disorder constitutes a medical emergency and warrants an expedited
      evaluation, diagnosis, and treatment to prevent the potential sequelae of
      permanent visual loss, endocrine abnormalities, or death. We report a case of
      sudden death from undiagnosed pituitary tumor apoplexy. The decedent was
      evaluated by medical personnel on three occasions in the week prior to her death
      for severe headache, nausea, vomiting, and photophobia. Postmortem examination
      demonstrated a hemorrhagic infarction of a pituitary adenoma with necrosis and
      expansion out of the sella turcica. The recognition of and treatment for a
      patient with pituitary tumor apoplexy requires a rapid multidisciplinary effort.
      Failure of prompt diagnosis may be fatal and require a medico-legal death
      investigation for sudden and unexpected death.

PMID- 21854389
TI  - Blood-brain barrier modeling with co-cultured neural progenitor cell-derived
      astrocytes and neurons.
AB  - In vitro blood-brain barrier (BBB) models often consist of brain microvascular
      endothelial cells (BMECs) that are co-cultured with other cells of the
      neurovascular unit, such as astrocytes and neurons, to enhance BBB properties.
      Obtaining primary astrocytes and neurons for co-culture models can be laborious,
      while yield and heterogeneity of primary isolations can also be limiting. Neural
      progenitor cells (NPCs), because of their self-renewal capacity and ability to
      reproducibly differentiate into tunable mixtures of neurons and astrocytes,
      represent a facile, readily scalable alternative. To this end, differentiated rat
      NPCs were co-cultured with rat BMECs and shown to induce BBB properties such as
      elevated trans-endothelial electrical resistance, improved tight junction
      continuity, polarized p-glycoprotein efflux, and low passive permeability at
      levels indistinguishable from those induced by primary rat astrocyte co-culture.
      An NPC differentiation time of 12 days, with the presence of 10% fetal bovine
      serum, was found to be crucial for generating NPC-derived progeny capable of
      inducing the optimal response. This approach could also be extended to human NPC
      derived astrocytes and neurons which similarly regulated BBB induction. The
      distribution of rat or human NPC-derived progeny under these conditions was found
      to be a roughly 3 : 1 mixture of astrocytes to neurons with varying degrees of
      cellular maturity. BMEC gene expression analysis was conducted using a BBB gene
      panel, and it was determined that 23 of 26 genes were similarly regulated by
      either differentiated rat NPC or rat astrocyte co-culture while three genes were
      differentially altered by the rat NPC-derived progeny. Taken together, these
      results demonstrate that NPCs are an attractive alternative to primary neural
      cells for use in BBB co-culture models.

PMID- 21854391
TI  - Anatomical localization of protease-activated receptor-1 and protease-mediated
      neuroglial crosstalk on peri-synaptic astrocytic endfeet.
AB  - We studied the localization, activation and function of protease-activated
      receptor 1 (PAR-1) at the CNS synapse utilizing rat brain synaptosomes and
      slices. Confocal immunofluoresence and transmission electron microscopy in brain
      slices with pre-embedding diaminobenzidine (DAB) immunostaining found PAR-1
      predominantly localized to the peri-synaptic astrocytic endfeet. Structural
      confocal immunofluorescence microscopy studies of isolated synaptosomes revealed
      spherical structures stained with anti-PAR-1 antibody which co-stained mainly for
      glial-filament acidic protein compared with the neuronal markers synaptophysin
      and PSD-95. Immunoblot studies of synaptosomes demonstrated an appropriate major
      band corresponding to PAR-1 and activation of the receptor by a specific agonist
      peptide (SFLLRN) significantly modulated phosphorylated extracellular signal
      regulated kinase. A significant membrane potential depolarization was produced by
      thrombin (1 U/mL) and the PAR-1 agonist (100 MUM) and depolarization by high K(+)
      elevated extracellular thrombin-like activity in the synaptosomes preparation.
      The results indicate PAR-1 localized to the peri-synaptic astrocytic endfeet is
      most likely activated by synaptic proteases and induces cellular signaling and
      modulation of synaptic electrophysiology. A protease mediated neuron-glia pathway
      may be important in both physiological and pathological regulation of the
      synapse.

PMID- 21854390
TI  - Induction of autophagy with catalytic mTOR inhibitors reduces huntingtin
      aggregates in a neuronal cell model.
AB  - Huntington's disease is a progressive neurodegenerative disorder caused by a CAG
      trinucleotide repeat expansion in the huntingtin gene. This expansion produces a
      mutant form of the huntingtin protein, which contains an elongated polyglutamine
      stretch at its amino-terminus. Mutant huntingtin may adopt an aberrant,
      aggregation-prone conformation predicted to start the pathogenic process leading
      to neuronal dysfunction and cell death. Thus, strategies reducing mutant
      huntingtin may lead to disease-modifying therapies. We investigated the
      mechanisms and molecular targets regulating huntingtin degradation in a neuronal
      cell model. We first found that mutant and wild-type huntingtin displayed
      strikingly diverse turn-over kinetics and sensitivity to proteasome inhibition.
      Then, we show that autophagy induction led to accelerate degradation of mutant
      huntingtin aggregates. In our neuronal cell model, allosteric inhibition of
      mTORC1 by everolimus, a rapamycin analogue, did not induce autophagy or affect
      aggregate degradation. In contrast, this occurred in the presence of catalytic
      inhibitors of both mTOR complexes mTORC1 and mTORC2. Our data demonstrate the
      existence of an mTOR-dependent but everolimus-independent mechanism regulating
      autophagy and huntingtin-aggregate degradation in cells of neuronal origin.

PMID- 21854392
TI  - Chronic psychosocial stress enhances long-term depression in a subthreshold
      amyloid-beta rat model of Alzheimer's disease.
AB  - In addition to genetic aspects, environmental factors such as stress may also
      play a critical role in the etiology of the late onset, sporadic Alzheimer's
      disease (AD). The present study examined the effect of chronic psychosocial
      stress in a sub-threshold Abeta (subAbeta) rat model of AD on long-term
      depression by two techniques: electrophysiological recordings of synaptic
      plasticity in anesthetized rats, and immunoblot analysis of memory- and AD
      related signaling molecules. Chronic psychosocial stress was induced using a rat
      intruder model. The subAbeta rat model of AD, which was intended to represent
      outwardly normal individuals with a pre-disposition to AD, was induced by
      continuous infusion of 160 pmol/day Abeta1-42 via a 14-day i.c.v. osmotic pump.
      Results from electrophysiological recordings showed that long-term depression
      evoked in stress/subAbeta animals was significantly enhanced compared with that
      in animals exposed to stress or subAbeta infusion alone. Molecular analysis of
      various signaling molecules 1 h after induction of long-term depression revealed
      an increase in the levels of calcineurin and phosphorylated CaMKII in groups
      exposed to stress compared with other groups. The levels of the brain-derived
      neurotrophic factor (BDNF) were significantly decreased in stress/subAbeta
      animals but not in stress or subAbeta animals. In addition, the levels of beta
      site amyloid precursor protein cleaving enzyme were markedly increased in
      stress/subAbeta. These findings suggest that chronic stress may accelerate the
      impairment of synaptic plasticity and consequently cognition in individuals 'at
      risk' for AD.

PMID- 21854393
TI  - Steroid receptor coactivator 2 modulates steroid-dependent male sexual behavior
      and neuroplasticity in Japanese quail (Coturnix japonica).
AB  - Steroid receptor coactivators are necessary for efficient transcriptional
      regulation by ligand-bound nuclear receptors, including estrogen and androgen
      receptors. Steroid receptor coactivator-2 (SRC-2) modulates estrogen- and
      progesterone-dependent sexual behavior in female rats but its implication in the
      control of male sexual behavior has not been studied to our knowledge. We cloned
      and sequenced the complete quail SRC-2 transcript and showed by semi-quantitative
      PCR that SRC-2 expression is nearly ubiquitous, with high levels of expression in
      the kidney, cerebellum and diencephalon. Real-time quantitative PCR did not
      reveal any differences between intact males and females the medial preoptic
      nucleus (POM), optic lobes and cerebellum. We next investigated the physiological
      and behavioral role of this coactivator using in vivo antisense oligonucleotide
      techniques. Daily injections in the third ventricle at the level of the POM of
      locked nucleic acid antisense targeting SRC-2 significantly reduced the
      expression of testosterone-dependent male-typical copulatory behavior but no
      inhibition of one aspect of the appetitive sexual behavior was observed. The
      volume of POM, defined by aromatase-immunoreactive cells, was markedly decreased
      in animals treated with antisense as compared with controls. These results
      demonstrate that SRC-2 plays a prominent role in the control of steroid-dependent
      male sexual behavior and its associated neuroplasticity in Japanese quail.

PMID- 21854394
TI  - Role of vesicle pools in action potential pattern-dependent dopamine overflow in
      rat striatum in vivo.
AB  - Action potential (AP) patterns and dopamine (DA) release are known to correlate
      with rewarding behaviors, but how codes of AP bursts translate into DA release in
      vivo remains elusive. Here, a given AP pattern was defined by four codes, termed
      total AP number, frequency, number of AP bursts, and interburst time [N, f, b,
      i].. The 'burst effect' was calculated by the ratio (gamma) of DA overflow by
      multiple bursts to that of a single burst when total AP number was fixed. By
      stimulating the medial forebrain bundle using AP codes at either physiological
      (20 Hz) or supraphysiological (80 Hz) frequencies, we found that DA was released
      from two kinetically distinct vesicle pools, the fast-releasable pool (FRP) and
      prolonged-releasable pool (PRP), in striatal dopaminergic terminals in vivo. We
      examined the effects of vesicle pools on AP-pattern dependent DA overflow and
      found, with given 'burst codes' [b=8, i=0.5 s], a large total AP number [N = 768,
      f = 80 Hz] produced a facilitating burst-effect (gamma[b8/b1] = 126 +/- 3%),
      while a small total AP number [N=96, 80 Hz] triggered a depressing-burst-effect
      (gamma[b8/b1] = 29 +/- 4%). Furthermore, we found that the PRP (but not the FRP)
      predominantly contributed to the facilitating-burst-effect and the FRP played an
      important role in the depressing-burst effect. Thus, our results suggest that
      striatal DA release captures pre-synaptic AP pattern information through
      different releasable pools.

PMID- 21854395
TI  - Hepatocyte growth factor stimulates root growth during the development of mouse
      molar teeth.
AB  - BACKGROUND AND OBJECTIVE: It is well known that tooth root formation is initiated
      by the development of Hertwig's epithelial root sheath (HERS). However,
      relatively little is known about the regulatory mechanisms involved in root
      development. As hepatocyte growth factor (HGF) is one of the mediators of
      epithelial-mesenchymal interactions in rodent tooth, the objective of this study
      was to examine the effects of HGF on the root development of mouse molars.
      MATERIAL AND METHODS: The HERS of mouse molars and HERS01a, a cell line
      originated from HERS, were used in this study. For detection of HGF receptors in
      vivo and in vitro, we used immunochemical procedures. Root development was
      assessed by implanting molar tooth germs along with HGF-soaked beads into kidney
      capsules, by counting cell numbers in HERS01a cell cultures and by performing a
      5'-bromo-2'-deoxyuridine (BrdU) assay in an organ-culture system. RESULTS: HGF
      receptors were expressed in the enamel epithelium of molar germs as well as in
      HERS cells. HGF stimulated root development in the transplanted tooth germs, the
      proliferation of HERS01a cells in culture and HERS elongation in the organ
      culture system. Examination using BrdU revealed that cell proliferation in HERS
      was increased by treatment with HGF, especially that in the outer layer of HERS.
      This effect was down-regulated when antibody against HGF receptor was present in
      the culture medium. CONCLUSION: Our results raise the possibility that HGF
      signaling controls root formation via the development of HERS. This study is the
      first to show that HGF is one of the stimulators of root development.

PMID- 21854396
TI  - In vitro and in vivo photodynamic activity of core-modified porphyrin IY69 using
      690 nm diode laser.
AB  - Core-modified porphyrins have been explored as the second-generation
      photosensitizers due to their excellent photophysical properties. IY69 [(5-phenyl
      10,15-bis(4-carboxylatomethoxyphenyl)-20-(2-thienyl)-21,23-dithiaporphyrin] was
      developed from the structure optimization guided by in vitro phototoxicity,
      showing potent activity (IC(50)=80 nm, broadband at 5 J cm(-2), R3230AC cells).
      The present study demonstrates in vivo photodynamic therapy (PDT) efficacy of
      IY69 using a murine tumor model (colon 26 cells on BALB/c mice) and 690 nm diode
      laser. In vitro phototoxicity of IY69 with the diode laser was compared with that
      with broadband light against colon 26 cells. Attenuation of the laser light by
      tissue samples was determined to estimate actual power density at targets.
      Biodistribution in various organs 24, 48, 72 h after i.p. administration was
      determined. Even though IY69 phototoxicity with the diode laser was less
      effective than that with the broadband light, the diode laser was quite effective
      in vitro (IC(50)=0.1 MUm, 10 J cm(-2), colon 26 cells). Concentration and light
      dose-dependent phototoxicity was observed. A significant light attenuation of 95%
      and 99% was observed by skin and 3 mm muscle with skin. IY69 PDT showed
      significant damage on tumor and delay in tumor growth in a dose-dependent manner.

PMID- 21854397
TI  - Absence of xenotropic murine leukemia virus-related virus in blood donors in
      China.
AB  - BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) is a novel
      human gammaretrovirus that was first identified in patients with prostate cancer
      in 2006. Subsequent studies have shown that XMRV is also detected in patients
      with chronic fatigue syndrome (CFS) and even in some healthy controls and blood
      donors. However, some conflicting findings have been reported by different
      laboratories or in different regions. The association of XMRV with human diseases
      and the prevalence of XMRV in different populations needs to be further
      determined. STUDY DESIGN AND METHODS: XMRV was screened in 391 blood samples from
      healthy blood donors in China. Nested reverse transcription-polymerase chain
      reaction (PCR) was used to amplify gag and env genes of XMRV from total RNA of
      peripheral blood mononuclear cells (PBMNCs) and plasma, respectively.
      Quantitative PCR was performed to detect XMRV env gene in genomic DNA of PBMNCs.
      To enhance the detection sensitivity, plasma was added into LNCaP cells to
      amplify XMRV in the plasma samples. RESULTS: No XMRV was found in the 391 blood
      donors in China or in the LNCaP cells inoculated with plasma from the blood
      donors. CONCLUSION: Both PCR and virus isolation in highly permissive LNCaP cells
      failed to detect XMRV in 391 Chinese blood donors, indicating that XMRV infection
      might not be present in blood donors in China.

PMID- 21854398
TI  - How do I transfuse platelets (PLTs) to reverse anti-PLT drug effect?
AB  - Antiplatelet agents (APAs) are commonly used in clinical practice to either treat
      or prevent arterial thrombotic disorders in patients at high risk. The newer APAs
      are more potent with higher bleeding risk profiles. Patients who present with
      serious bleeds or need urgent surgical interventions while on APAs may require
      reversal of these agents' effect on PLTs. Currently, there are no guidelines for
      management of such patients. This article describes my approach to PLT
      transfusion or use of pharmacologic agents in such clinical scenarios based
      solely on personal experience and very limited published data.

PMID- 21854399
TI  - Clinical value of negative skin tests to gadolinium contrast agents.

PMID- 21854400
TI  - The devil you know: parents seeking information online for paediatric cancer.
AB  - There is a growing interest in understanding the effect that online information
      seeking has on patients' experiences, empowerment and interactions with
      healthcare providers. This mixed-methods study combines surveys and in-depth
      interviews with 41 parents of paediatric cancer patients in the USA to examine
      how parents think about, evaluate, access and use the internet to seek
      information related to their child's cancer. We find that, during the acute
      crisis of a child being diagnosed with cancer, parents preferred to receive
      information related to their child's diagnosis, prognosis and treatment options
      from a trusted healthcare provider rather than through the internet. We find that
      access to medically related cancer information through the internet was deemed to
      be untrustworthy and frightening. Parents' reasons for avoiding online
      information-seeking included fear of what they might find out, uncertainty about
      the accuracy of information online, being overloaded by the volume of information
      online and having been told not to go online by oncologists. Some parents also
      had logistical barriers to accessing the internet. While most parents did not
      turn to the internet as a source of health-related information, many did use it
      to connect with sources of social support throughout their child's illness.

PMID- 21854401
TI  - Review article: the impact of bariatric surgery on gastrointestinal motility.
AB  - BACKGROUND: Obesity is a major medical problem worldwide. Different treatment
      modalities have emerged to treat obese patients, but the best long-term results
      are achieved with bariatric surgery. Currently, the interventions most commonly
      performed are laparoscopic adjustable gastric banding (LAGB), Roux-en-Y- gastric
      bypass (RYGB) and sleeve gastrectomy. AIM: To review the gastrointestinal motor
      complications associated with each of these types of bariatric interventions and
      the clinical implications of such complications. METHODS: Search of medical
      database (PubMed) on English-language articles from January 1996 to March 2011.
      The search terms used were laparoscopic adjustable gastric banding (LAGB), sleeve
      gastrectomy (LSG), roux-en-Y-gastric bypass (RYGB), using the AND operator with
      the terms: complications, motility, GERD, reflux, gastric emptying, esophagitis,
      dysphagia. RESULTS: Of the three bariatric interventions reviewed, LAGB was the
      most studied. Most studies reported short follow-up, of <= 1 year. Oesophageal
      motor dysfunction is the most common motility complication following the
      bariatric interventions that were reviewed and is mainly observed after LAGB.
      Some data suggest that oesophageal motor function testing predicts development of
      post-operative symptoms and oesophageal dilation. RYGB offers protection from
      gastro-oesophageal reflux. Sleeve gastrectomy was the least studied and was
      associated with an acceleration of gastric emptying. CONCLUSIONS: The effects of
      these interventions on GI motility should be considered when selecting patients
      for bariatric surgery. There is scant information regarding the overall effect of
      sleeve gastrectomy on gastro-oesophageal reflux patterns and oesophageal
      motility.

PMID- 21854402
TI  - Total and free testosterone concentrations are strongly influenced by age and
      central obesity in men with type 1 and type 2 diabetes but correlate weakly with
      symptoms of androgen deficiency and diabetes-related quality of life.
AB  - OBJECTIVE: Testosterone levels are commonly lowered in men with diabetes, but it
      is unclear how these relate to symptoms of hypogonadism and quality of life. We
      sought to investigate the relationship between testosterone levels, symptoms of
      androgen deficiency, erectile function and quality of life in men with type 1 and
      type 2 diabetes. DESIGN AND SUBJECTS: Cross-sectional study of 115 men with type
      2 diabetes, 93 men with type 1 diabetes and 121 healthy controls. MEASUREMENTS:
      Total, bioavailable and free testosterone levels were measured or calculated by
      Vermuelen's formula. Quality of life and symptom scores were assessed by the
      Audit of Diabetes Dependent Quality of Life (ADDQoL), androgen deficiency in the
      aging male (ADAM) and International Index of Erectile Function (IIEF)
      questionnaires. RESULTS: Forty-five and sixty-one per cent of men with type 2
      diabetes had low total and calculated free testosterone (CFT) levels,
      respectively. Total testosterone (TT) levels were not lowered in men with type 1
      diabetes, but 32% had low CFT. After adjustment for age and waist circumference,
      only CFT in men with type 2 diabetes (-0.037 nm, 95% CI -0.075 to -0.0003, P =
      0.048) remained lowered compared with controls. CFT correlated weakly with ADAM
      (r = -0.26, 95% CI -0.42 to -0.08, P = 0.006), IIEF (r = 0.19, 95% CI 0.01-0.37,
      P = 0.042) and ADDQoL (r = 0.21, 95% CI 0.03 to 0.38, P = 0.022) scores in men
      with type 2, but not type 1 diabetes. Age exerted the predominant effect on
      erectile function in both groups, in a model incorporating age, testosterone
      level and complications. CONCLUSIONS: Testosterone levels are strongly affected
      by age and central obesity in men with type 1 and type 2 diabetes but correlate
      weakly with symptoms of androgen deficiency and erectile function. Testosterone
      levels do not appear to be a major determinant of quality of life in patients
      with diabetes.

PMID- 21854403
TI  - Development of hypothyroidism during long-term follow-up of patients with toxic
      nodular goitre after radioiodine therapy.
AB  - OBJECTIVE: To investigate the cure rate and incidence of hypothyroidism of
      radioiodine treatment with a calculated dose regimen and an intended thyroid dose
      of 150 Gy in patients with toxic nodular goitre during long-term follow-up.
      PATIENTS: A total of 265 consecutive patients with toxic nodular goitre were
      treated between March 2003 and August 2004 at our institute and followed up for a
      maximum of 8 years. Preliminary radioiodine testing with volumetric measurement
      of the thyroid by ultrasound as well as individual thyroidal radioiodine uptake
      and half-life measurements were performed before radioiodine therapy. The
      estimated radiation dose to the thyroid was 150 Gy. MEASUREMENTS: Follow-up
      controls with respect to success of therapy and development of hypothyroidism
      were performed 3 months, 1 and up to 8 years after radioiodine treatment. The
      relation of the achieved thyroid dose to the success rate of treatment and to the
      incidence of hypothyroidism was analysed. RESULTS: The cure rates were 85% at 3
      months, 98% at 1 year and 98% at the end of follow-up. Above an achieved thyroid
      dose of more than 120 Gy, there was no significant association between the dose
      achieved in the thyroid and the cure rate on follow-up. The incidences of
      hypothyroidism at 3 months, at 1 year and at the end of follow-up were 32%, 55%
      and 73%, respectively. CONCLUSIONS: Radioiodine treatment with a calculated dose
      regimen is a highly effective treatment option in patients with toxic goitre with
      an overall success rate of 98%. However, radioiodine treatment with an intended
      thyroid dose of 150 Gy leads to a high incidence of hypothyroidism on long-term
      follow-up. This finding supports the suggestion that in future intended thyroid
      doses could be lowered in patients treated with a calculated dose regimen for
      toxic nodular goitre.

PMID- 21854404
TI  - Glucose fluctuations in subjects with normal glucose tolerance, impaired glucose
      regulation and newly diagnosed type 2 diabetes mellitus.
AB  - OBJECTIVE: Glycemic variability is poorly studied in the nondiabetic individuals
      and newly diagnosed patients with type 2 diabetes. The aim of the study is to
      investigate the characteristics of glucose fluctuations in subjects with normal
      glucose tolerance (NGT), impaired glucose regulation (IGR) and newly diagnosed,
      drug-naive type 2 diabetes mellitus (DM-2). DESIGN AND PATIENTS: This is a cross
      sectional study of three groups including 53 subjects with IGR, 56 DM-2 patients
      and 53 NGT individuals. Monitoring by a continuous glucose monitoring system
      (CGMS((r)) System Gold(TM)) was performed for three consecutive days.
      MEASUREMENTS: Mean blood glucose (MBG), standard deviation of MBG (SDBG), largest
      amplitude of glycemic excursions (LAGE) and mean amplitude of glycemic excursions
      (MAGE) were calculated to estimate intraday blood glucose variability. Interday
      variability of glucose was evaluated by absolute means of daily differences
      (MODD). Postprandial glucose excursion (PPGE) was calculated to assess the
      influence of meals on glucose fluctuation. RESULTS: Twenty-two percentage of NGT
      and 33.9% of IGR individuals experienced blood glucose >= 11.1 mmol/l; 49.1% of
      NGT, 50.9% of IGR and 30.8% of DM-2 participants had hypoglycemic episodes (CGM
      values <3.9 mmol/l). The IGR and DM-2 groups had greater SDBG (P = 0.010 and P <
      0.001), LAGE (P = 0.014 and P < 0.001) and MAGE (P = 0.044 and P < 0.001)
      compared with the NGT group. Significantly greater MODD and PPGEs were found in
      the DM-2 groups than in the IGR and NGT groups (P < 0.001). The DM-2 patients had
      higher 72-MBG and glucose levels overnight than the NGT and IGR subjects (P <
      0.001). In the patients with diabetes, MAGE was positively associated with MODD
      (r = 0.558, P < 0.001) and PPGEs (r = 0.738-0.843, P < 0.001). CONCLUSIONS:
      Glucose variability is present to an increasing degree from NGT to IGR and IGR to
      DM-2. Compared with the NGT individuals, the IGR and DM-2 subjects show more
      predominant intraday glucose fluctuations. The DM-2 patients demonstrate
      increased PPGEs, higher glucose levels overnight and greater interday
      fluctuations.

PMID- 21854405
TI  - Clinical relevance of cardiac structure and function abnormalities in patients
      with Cushing's syndrome before and after cure.
AB  - OBJECTIVES:   Sustained hypercortisolism impacts cardiac function, and, indeed,
      cardiac disease is one of the major determinants of mortality in patients with
      Cushing's syndrome. The aim of this study was to assess the clinical relevance of
      cardiac structure and function alterations by echocardiography in patients with
      active Cushing's syndrome and after disease remission. STUDY DESIGN:   Seventy
      one patients (61 women, 10 men) with Cushing's syndrome and 70 age-, sex- and
      blood pressure-matched controls were enrolled. Echocardiography was performed in
      49 patients with active disease and at several time points after remission in 44
      patients (median follow-up 46.4 months), and prevalence of abnormal left
      ventricular mass measurements and systolic and diastolic functions indices was
      compared between patients with active disease, after remission and controls.
      Twenty-two patients were evaluated both before and after remission. RESULTS:   Up
      to 70% of patients with active Cushing's syndrome presented abnormal left
      ventricular mass parameters; 42% presented concentric hypertrophy and 23%
      concentric remodelling. Major indices of systolic and diastolic functions, i.e.
      ejection fraction and E/A ratio, respectively, were normal. Upon remission of
      hypercortisolism, left ventricular mass parameters ameliorated considerably,
      although abnormal values were still more frequent than in controls. Both cortisol
      excess and hypertension contribute to cardiac mass alterations and increase the
      prevalence of target organ damage. CONCLUSIONS:   Cushing's syndrome is
      associated with an increased risk for abnormalities of cardiac mass, which
      ameliorates, but does not fully disappear after remission. Systolic and diastolic
      functions are largely within the normal range in these patients.

PMID- 21854406
TI  - Effects of type I protein kinase A modulation on the T cell distal pole complex.
AB  - The distal pole complex (DPC) assembles signalling proteins at the T cell pole
      opposite the immunological synapse (IS) and is thought to facilitate T cell
      activation by sequestering negative regulatory molecules away from the T cell
      receptor-proximal signalling machinery. Here, we report the translocation of type
      I protein kinase A (PKA) to the DPC in a fraction of T cells following activation
      and the localization of type I PKA with known components of the DPC. We propose
      that sequestration of type I PKA and concomitant loss of cAMP-mediated negative
      regulation at the IS may be necessary to allow full T cell activation. Moreover,
      composition of the DPC appears to be modulated by type I PKA activity, as the
      antagonist Rp-8-Br-cAMPS inhibited translocation of type I PKA and other DPC
      proteins.

PMID- 21854407
TI  - Age-dependent alterations of HLA-DR expression and effect of lipopolysaccharide
      on cytokine secretion of peripheral blood mononuclear cells in the elderly
      population.
AB  - HLA-DR, a major histocompatibility complex, MHC class II, is involved in several
      autoimmune conditions, disease susceptibility and disease resistance. Here, we
      investigate the impact of different age individuals on HLA-DR expression on
      peripheral blood mononuclear cells (PBMCs) induced by lipopolysaccharide (LPS).
      The results indicate that HLA-DR expression on PBMCs in the population aged above
      70 years significantly increased as compared with that in the lower-age groups by
      flow cytometry analysis (B-D; r = 0.690, P = 0.000265). In addition, followed by
      LPS stimulation, the levels of cytokine TNF-alpha, IL-6 and IL-10 secretion by
      allogeneic T lymphocytes from different age groups (A-D) were significantly
      increased (P < 0.05). Notably, levels of TNF-alpha and IL-6 were significantly
      reduced in groups B, C and D as compared with group A (P < 0.05), whereas levels
      of IL-10 increased (P = 0.012). However, no significant difference in PBMC
      secreted TNF-alpha, IL-6 and IL-10 levels was observed among groups A, B, C and D
      (P > 0.05) before LPS stimulation. We firstly present data showing an age
      dependent increase in HLA-DR expression in the population aged above 70 years and
      the individual with aged above 70 years has reduced the secretion of inflammatory
      mediators (TNF-alpha and IL-6) by PBMCs and increased the secretion of anti
      inflammatory cytokine (IL-10) after LPS stimulation in vitro. The better
      understanding of HLR-DR expression on human PBMCs in aged individuals and its
      relation to the host cellular immunity would provide important insights into the
      immunity of aged individuals and particularly, in elderly patients with sepsis.

PMID- 21854408
TI  - Rough-Form Lipopolysaccharide Increases Apoptosis in Human CD4+ and CD8+ T
      Lymphocytes.
AB  - Immunosuppression induced by lymphocyte apoptosis is considered an important
      factor in the pathogenesis of sepsis and has been demonstrated in both animal
      models of lipopolysaccharide (LPS)-induced endotoxemia and septic patients. As
      rough-form LPS (R-LPS) has recently been shown to elicit a stronger immunological
      response than regular smooth-form LPS (S-LPS), we aimed to assess the apoptosis
      inducing capabilities of R-LPS in different subsets of lymphocytes (CD4(+) T
      cells, CD8(+) T cell, B cells and NK cells). Using multicolour flow cytometry on
      human peripheral blood mononuclear cells, we found that R-LPS increased apoptosis
      in CD4(+) and CD8(+) T cells assessed by annexin V and propidium iodide (AV(+)
      PI(-)), compared with both S-LPS-stimulated and unstimulated cells. 7-Amino
      actinomycin D and staining for intracellular active caspase-3, which are
      considered later signs of apoptosis, did not reveal the same results. Both forms
      appeared to inhibit apoptosis in B cells, but no LPS-form-specific effect was
      seen on B or NK cells. Our results indicate that R-LPS induces a stronger AV(+)
      PI(-)-assessed apoptotic response in T cells than S-LPS. Our findings emphasize
      the importance of T cell apoptosis in endotoxemia and advocates for control of
      LPS form in both endotoxemia research and clinical trials with Gram-negative
      infections.

PMID- 21854409
TI  - Characterization of monocyte-derived dendritic cells from patients with active
      and treated paracoccidioidomycosis.
AB  - Cellular immune responses are a significant defence mechanism in human
      paracoccidioidomycosis (PCM), an endemic mycosis in Latin America; however,
      little is known about the role of dendritic cells (DCs) in human PCM. We
      investigated monocyte-derived DCs from patients with treated (TP) and active PCM
      (AP) compared with healthy non-PCM donors (CO). DCs from the TP group showed
      higher expression of HLA-DR, CD86 and DC-SIGN compared with CO, whereas AP showed
      similar expression to CO. Production of IL-10 was downregulated by TNF-alpha in
      all groups and lower levels were observed in untreated DCs from AP compared with
      CO. Conversely, IL-12p40 was significantly upregulated in the DCs of the TP
      group. TNF-alpha-activated DCs from the CO group produced significantly lower
      levels of IL-12p40 when differentiated from magnetic-sorted monocytes (MACS)
      compared with adhered monocyte-derived DCs. This comparison in the TP group
      revealed similar levels of IL-12p40, suggesting a T cell-independent increase in
      the production of IL-12p40. Higher expression of surface molecules with increased
      IL-12p40 may indicate a better activation of DCs after the treatment of PCM. Our
      findings suggest that DCs may be crucial in the protective response to
      Paracoccidioides brasiliensis and that in vitro-generated DCs might be useful in
      enhancing antifungal immunity, especially during active PCM.

PMID- 21854410
TI  - Difference in dental arch size between obese and non-obese patients with
      obstructive sleep apnoea.
AB  - A large tongue is recognised as a factor that increases the collapsibility of the
      upper airway in obstructive sleep apnoea (OSA) patients. We hypothesised that the
      propensity to develop severe OSA could be minimised if the dental arches were
      enlarged in obese OSA people who are thought to have a large tongue. We therefore
      compared the size of the dental arches in obese and non-obese OSA patients. Using
      a lateral cephalogram and study models, we compared the sizes of the tongue and
      dental arches in 23 obese and 23 non-obese Japanese male OSA patients, who were
      matched for age, apnoea hypopnea index (AHI) and maxillomandibular size. The
      median age (years) and AHI (events per hour) for the obese and non-obese groups
      were 36.5 and 39.0, and 13.4 and 14.3, respectively. The maxillomandibular size
      was matched with regard to SNA, SNB and lower face cage obtained from
      cephalometric measurements. The parameters that were measured for the study model
      included dental arch width, dental arch length, overjet and overbite. Tongue size
      (P < 0.05) and both upper (P < 0.01) and lower (P < 0.05) dental arch widths were
      significantly larger in obese than in non-obese OSA patients, and there was no
      difference in the severity of OSA between the two groups. These findings suggest
      that the tongue was larger and dental arches were enlarged in obese patients
      compared with non-obese patients under the same disease severity. Wider dental
      arches in obese OSA patients may help to offset the impact of the enlarged tongue
      on upper airway patency.

PMID- 21854411
TI  - Phototoxic dermatitis due to Chenopodium album in a child.
AB  - In this article, we report a 2-year-old girl with severe phototoxic dermatitis
      caused by ingestion of Chenopodium album. To the best of our knowledge, this is
      the first case of phototoxic dermatitis due to Chenopodium album in childhood.

PMID- 21854412
TI  - The dermoscopic features in infantile hemangioma.
AB  - Dermoscopy is useful for evaluating the precise vascular structure. We recently
      applied dermoscopy to infantile hemangiomas without proliferation and showed
      polymorphous vascular structures. We now demonstrate two typical dermoscopic
      figures of proliferative infantile hemangiomas. One was a superficial hemangioma
      which showed polymorphous vascular structure without obvious red linear vessels
      and red dilated vessels. The other was a thicker hemangioma with a deeper
      component. This hemangioma had polymorphous vascular structures with red linear
      and red dilated vessels. These observations indicates the usefulness of
      dermoscopy for subclassifying infantile hemangioma.

PMID- 21854413
TI  - Severe atopic dermatitis and transient hypogammaglobulinemia in children.
AB  - We sought to describe the clinical outcomes of eight pediatric patients diagnosed
      with atopic dermatitis (AD) and hypogammaglobulinemia through retrospective
      review of medical records. All patients presented with severe facial AD. The mean
      and median ages of diagnosis of hypogammaglobulinemia were 6.2 months and 6.5
      months, respectively, with a mean immunoglobulin G (IgG) level of 156 mg/dL.
      Seven of the eight patients identified in our search demonstrated simultaneous
      improvement in AD and serum IgG levels within 2 years of initial presentation,
      suggesting a diagnosis of transient hypogammaglobulinemia. The remaining patient
      demonstrated normalization by age 6, but no IgG levels had been measured between
      initial presentation and age 6. The five patients who were tested for specific
      antibody response to tetanus and Haemophilus influenzae type b vaccination all
      produced protective responses. All eight patients initially presented with high
      serum IgE levels. On initial evaluation, three patients had leukocytosis (white
      blood cell count >18,000 cells/MUL), and six had peripheral blood eosinophilia.
      Three patients outgrew their AD by age 5, and five had clinically good to
      excellent control of their AD at their last visit, coincident with normalization
      of IgG levels. Although severe AD and immunoglobulin deficiency may rarely be
      associated with complex immunodeficiency disorders, our observations suggest
      that, with careful immunologic monitoring and diligent skin care, most children
      who present with severe AD and hypogammaglobulinemia exhibit improvement in
      dermatitis and serum IgG levels within 2 years of onset without major
      complications.

PMID- 21854414
TI  - Vitiligo in children: a clinical-epidemiologic study in Jordan.
AB  - Two thousand consecutive children were analyzed in a 2-year period to establish a
      clinical and epidemiologic profile of vitiligo in Jordan; 71 had vitiligo, with
      the prevalence increasing with age (0.45% <1 yr, 1% aged 1-5 yrs, 2.1% aged 5-12
      yrs). Nonsegmental-type vitiligo was seen in 67 of the patients (92.9%).

PMID- 21854415
TI  - Diffuse cutaneous mastocytosis masquerading as epidermolysis bullosa.
AB  - A 10-month-old boy presented with a history of a generalized cutaneous bullous
      eruption since 3 months of age. Emesis, flush, pruritus, and fatigue had
      accompanied relapsing episodes of sometimes extensive blistering. Histopathology
      showed dense dermal infiltrates of mast cells on hematoxylin and eosin and
      corroborating immunohistochemical staining. Laboratory examination revealed a
      markedly high level of serum tryptase. Based on these results and after
      consecutive staging, the patient was diagnosed with diffuse cutaneous bullous
      mastocytosis (BM). Mutation analysis detected a deletion mutation (del419) in C
      Kit by direct exon sequencing. This rare entity must be considered in the
      differential diagnosis whenever a child presents with bullae and erosions. A
      crucial diagnostic hint is that rubbing of affected skin areas results in
      whealing (Darier's sign). A comprehensive diagnostic approach, advanced
      therapeutic strategies, regular follow-ups, and instruction of patients and
      relatives on prevention and prophylaxis are highly indicated.

PMID- 21854416
TI  - Local vaccine site reactions and contact allergy to aluminum.
AB  - Childhood vaccines are a routine part of pediatric care in the United States;
      clinicians must be able to recognize and interpret associated localized adverse
      reactions. Redness and induration at the site of injection are commonly reported
      and are considered to be the result of local inflammation or hematoma formation,
      although other atypical reactions can occur. We report the case of a 6-month-old
      infant who developed subcutaneous nodules at the sites of his 4- and 6-month
      Pentacel (DTaP/Hib/IPV, diphtheria, tetanus, acellular pertussis, Haemophilus b
      conjugate, and inactivated poliovirus vaccine) and 6-month Prevnar (heptavalent
      pneumococcal vaccine) injections. Infectious disease and immunodeficiency
      examinations were unremarkable. Aluminum contact allergy was considered, and
      contact allergy testing confirmed sensitivity to aluminum. Although rare,
      aluminum contact allergy after routine immunization can occur and should be
      considered in the differential diagnosis of persistent subcutaneous nodules after
      vaccination.

PMID- 21854417
TI  - Delineating capillary malformations in the operating suite using white eyeliner
      pencil.
AB  - Delineating the extent of capillary malformations in the operating suite can be
      challenging because of a variety of physiologic modifiers, including
      vasodilatation induced by anesthesia, reactive erythema, and filtering of colors
      with protective laser eyewear. The use of traditional surgical pens to mark the
      treatment field has limitations; we have found the use of a white eyeliner pencil
      to delineate lesions a contemporary technique that assists in identifying the
      target tissue intraoperatively.

PMID- 21854418
TI  - Early and successful enzymatic debridement via collagenase application to pinna
      in a preterm neonate.
AB  - We report early and successful enzymatic debridement using collagenase
      application to pinna in a preterm neonate. Collagenase clostridiopeptidase A
      should be kept in mind not only for the removal of eschar but also for avoidance
      of the progression of necrotic tissue in neonates.

PMID- 21854419
TI  - Propranolol for recalcitrant ulcerated hemangioma of infancy.
AB  - Hemangioma of infancy (HOI) is a common, self-resolving, benign tumor that
      frequently requires no intervention. Ulceration is one of the main complications
      of HOI, and active treatment is usually required to manage pain, potential
      scarring, and occasionally bleeding and infection. Since the discovery that oral
      propranolol is an effective treatment for complicated HOI, it has been replacing
      systemic corticosteroids as first-line therapy, and early recommendations for
      treatment protocols have been devised. We report the successful treatment of six
      children with recalcitrant ulcerated HOI using propranolol. In all cases,
      complete, rapid healing occurred. Two children experienced recurrence of
      ulceration after ceasing propranolol, but this was rapidly controlled by
      restarting treatment. No adverse effects were encountered. We propose that
      ulceration in HOI is an indication for propranolol treatment if more conservative
      therapies have failed.

PMID- 21854420
TI  - Postvaccination morphea profunda in a child.
AB  - We report a new case of postvaccination morphea profunda (MP) in a child and
      discuss its different clinical presentations, prognosis, and therapy and its
      relationship with "solitary morphea profunda." A 2-year-old healthy girl
      presented with an induration of the anterior aspect of the left thigh of 9 months
      duration. The lesion had appeared 3 months after a third dose of diphtheria
      tetanus-pertussis vaccine. Cutaneous examination showed an induration of 7 * 7 cm
      with an "orange peel" texture after pinching the skin. Histologic examination
      confirmed the diagnosis of MP. Systemic steroids (1 mg/kg/day) led to the
      stabilization of the lesion. After 4 months of treatment, we began the
      concomitant use of oral methotrexate (10 mg/wk) for 2 months. Methotrexate was
      then continued alone for 10 months, leading to a significant regression of the
      induration with no relapse.

PMID- 21854421
TI  - Sole dermatitis in children: patch testing revisited.
AB  - Although dermatoses affecting the soles of the feet in children are regularly
      encountered in dermatology clinics, the relationship with allergic contact
      dermatitis affecting this part of the foot is not well established. The aim of
      this study was to evaluate the relevance of patch testing children with sole
      dermatoses. We reviewed the results of all patch tests performed in children (<18
      years) presenting with dermatoses involving the soles between 1997 and 2009 from
      our departmental patch test database. Forty-one children were identified: 27
      children with an inflammatory dermatitis affecting the sole and 14 children with
      juvenile plantar dermatosis (JPD). Seventeen (41%) children had at least one
      clinically relevant positive patch test reaction. Rubber additives and potassium
      dichromate were the most frequent allergens identified. Forty-eight percent of
      children with inflammatory dermatitis affecting the sole and 29% of children with
      JPD had at least one relevant reaction. Of the children with relevant reactions,
      76% had a personal or family history of atopy. Our results demonstrate the
      importance of patch testing children with dermatoses affecting the soles and
      indicate that a history of atopy or a diagnosis of JPD should not deter
      investigation.

PMID- 21854422
TI  - A display of combined left ventricular function and dyssynchrony using Doppler
      tissue imaging: its application in acute response to cardiac resynchronization
      therapy.
AB  - BACKGROUND: We have recently proposed a novel method for displaying left
      ventricular (LV) function and mechanical dyssynchrony, which is based on the
      "vector analysis" using Doppler tissue imaging (DTI). The aim of this study was
      to examine acute-phase impact of cardiac resynchronization therapy (CRT) on the
      parameters assessed by this method. METHODS: We studied a total of 25 patients
      with systolic heart failure, 14 undergoing simultaneous acute pacing-hemodynamic
      study and DTI; and 11 patients DTI within a few days before and one week after
      CRT. Parameters derived from the displaying method were followings: (1)
      percentage area of the hexagon, the area divided by the overall graph area,
      reflecting global LV systolic function; (2) net-delay magnitude, the length of
      the composite vector for the six vectors, a dyssynchrony index; and (3) delayed
      contraction site, graphical position of the composite vector. RESULTS: CRT
      significantly increased cardiac output (3.1 +/- 1.0 to 3.4 +/- 0.7 L/min, P =
      0.02) and +dp/dt (782 +/- 149 to 1,089 +/- 270 mm Hg/s, P < 0.01), and decreased
      mitral regurgitaion jet area (7.9 +/- 3.0 to 4.8 +/- 2.4 cm(2) , P < 0.01). As
      with the new method, there were significant decreases in the percentage area of
      the hexagon (20.7 +/- 6.6 to 18.6 +/- 6.5%, P < 0.01) and the net-delay magnitude
      (122 +/- 59 to 72 +/- 48 ms, P < 0.01). The reduction of net-delay magnitude
      accompanied alteration of delayed contraction site; 16 patients had the most
      delayed site between the lateral and inferior segments before CRT, and seven
      patients after CRT (P = 0.02). CONCLUSIONS: The new method would be a useful tool
      to assess efficacy of CRT in patients with systolic heart failure.

PMID- 21854423
TI  - Impact of obesity on left ventricular geometry and function in pediatric patients
      after successful aortic coarctation repair.
AB  - AIMS: To evaluate if obesity has an additional negative impact on left
      ventricular (LV) geometry and function in normotensive pediatric patients >12
      months after successful treatment of aortic coarctation (CoA). METHODS AND
      RESULTS: We studied 40 CoA patients (mean age 14 +/- 3 years, and male sex 70%),
      of them 10 were obese and 30 lean. Both groups were age and sex comparable. The
      entire studied sample underwent 24-ambulatory blood pressure (BP) monitoring,
      standard echocardiographic evaluation, and speckle tracking study. Both office
      and 24-hour diastolic BP were significantly increased in obese patients. Obese
      CoA patients showed increased LV mass (52 +/- 13 g/m(2.7) vs. 43 +/- 9 g/m(2.7) ,
      P = 0.02), and significant reduction in E/A compared with lean CoA patients.
      Myocardial deformation properties were significantly reduced in obese CoA
      patients in all the three studied planes (longitudinal, radial, and
      circumferential) compared with CoA lean patients. LV twist values showed a
      significant reduction in the obese CoA group (9.9 degrees  +/- 2.2 degrees  vs.
      14.5 degrees  +/- 2.3 degrees , P < 0.0001). CONCLUSIONS: Our study shows that
      obesity in successfully treated CoA children, has an additional negative effect
      on BP, LV mass, and cardiac function. These findings are of particular concern,
      since life expectancy in CoA patients is limited mainly by atherosclerosis, and
      all the obesity-associated abnormalities found are harbingers of higher
      cardiovascular risk.

PMID- 21854424
TI  - Dynamic changes in microcirculatory blood flow during dobutamine stress assessed
      by quantitative myocardial contrast echocardiography.
AB  - BACKGROUND: Although dobutamine-atropine stress echocardiography (DASE) has been
      widely used for evaluating patients with coronary artery disease (CAD), dynamic
      changes that occur at microcirculatory level during each stage of stress have not
      been demonstrated in humans. AIM: We sought to determine variations in myocardial
      blood flow (MBF) during DASE using quantitative real time myocardial contrast
      echocardiography (RTMCE). METHODS: We studied 45 patients who underwent coronary
      angiography and RTMCE. Replenishment velocity of microbubbles in the myocardium
      (beta) and MBF reserves were obtained at baseline, intermediate stage (70% of
      maximal predicted heart rate), peak stress, and recovery phase. RESULTS: beta and
      MBF reserves were lower in patients with than without CAD at intermediate (1.65
      vs. 2.10; P=0.001 and 2.44 vs. 3.23; P=0.004) and peak (1.63 vs. 3.00; P<0.001
      and 2.14 vs. 3.98; P<0.001, respectively). In patients without CAD, beta, and MBF
      reserves increased from intermediate to peak and decreased at recovery, while in
      those without CAD reserves did not change significantly. Optimal cutoff values of
      beta reserve at intermediate, peak, and recovery were 1.78, 2.09, and 1.70, with
      areas under the curves of 0.80 (95%CI=0.67-0.94), 0.89 (95%CI=0.79-0.99), and
      0.69 (95%CI=0.53-0.85). Sensitivity, specificity and accuracy for detecting CAD
      at intermediate stage were 68% (95%CI=48-89), 85% (95%CI=71-98), and 78%
      (95%CI=66-90), at peak stress were 79% (95%CI=61-97), 96% (95%CI=89-100), and 89%
      (95%CI=80-98), and at recovery were 74% (95%CI=54-93), 65% (95%CI=47-84), and 69%
      (95%CI=55-82), respectively. CONCLUSION: RTMCE allows for quantification of
      dynamic changes in microcirculatory blood flow at each stage of DASE. The best
      parameter for detecting CAD in all stages was beta reserve.

PMID- 21854425
TI  - Echocardiographic characteristics of intravenous leiomyomatosis with intracardiac
      extension: a single-institution experience.
AB  - BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare smooth-muscle
      proliferation arising from a uterine myoma and occasionally extending into
      cardiac chambers. METHODS AND RESULTS: A series of 10 consecutive patients with
      histologically and surgically proven intracardiac IVL between 2000 and 2010 in
      our hospital were reviewed. The echocardiographic features of 10 cases with IVL
      and extensive spread into the right-sided cardiac chambers were described for the
      first time. All patients were female and the mean age was 42+/-7 years old. The
      first symptoms of six patients (60%) were exertional dyspnea and palpitation of
      cardiac origin. Echocardiography showed that all the tumors originated from the
      inferior vena cava (IVC) and located in cardiac right chambers (70% in right
      atrium alone, 30% in right ventricle and atrium). Eight masses (80%) were oval,
      whereas the others (20%) were serpentine, all with well-demarcated borders and
      most (70%) with heteroechogenic texture. Five tumors (50%) intermittently
      prolapsed into right ventricle through the tricuspid valve. Two patients with
      nodules adhering to the top of the tumors had pulmonary tumorous thromboembolism.
      CONCLUSION: Echocardiography is a simple and important technique to diagnose IVL
      with intracardiac extension. This disease should be considered in a female
      patient presenting with an extensive mass from IVC with well-demarcated border in
      the right-sided cardiac chambers.

PMID- 21854426
TI  - Preoperative assessment of mitral valve prolapse and chordae rupture using real
      time three-dimensional transesophageal echocardiography.
AB  - BACKGROUND: Mitral valve (MV) repair provides a better outcome in patients with
      significant mitral regurgitation than MV replacement. Valve repair requires a
      thorough understanding of MV morphology. Recently developed real time three
      dimensional transesophageal echocardiography (RT3D TEE) can provide online
      acquisition and accurate information of cardiac structures. The study aim was to
      evaluate the feasibility and accuracy of using RT3D TEE to assess mitral valve
      prolapse (MVP) and chordae rupture for surgical planning purposes. METHODS: Fifty
      six consecutive patients with moderate to severe mitral regurgitation due to MVP
      received two-dimensional (2D) TEE and RT3D TEE the day before operation. The
      accuracy of the assessment of MVP and chordae rupture by RT3D TEE was determined
      and compared with assessment by 2D TEE using surgical inspection as the gold
      standard. RESULTS: The overall sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of 2D TEE in detection of MVP
      were 87%, 96%, 93%, 88%, and 95%, respectively, whereas those of RT3D TEE were
      100%, 99%, 99%, 98%, and 100%, respectively (P<0.05 for all comparisons). The
      receiver operating characteristic (ROC) curve areas for assessment of anterior
      leaflet and posterior leaflet segment involvement using RT3D TEE (ROC areas 0.96
      and 0.99) were higher than for those using 2D TEE (ROC areas 0.86 and 0.94).
      Interobserver agreement for RT3D TEE (kappa=0.97, 95% confidence interval [CI]
      0.92-1.00) was significantly greater than for 2D TEE (kappa=0.89, 95% CI 0.81
      0.93) (P<0.05). CONCLUSION: RT3D TEE is a feasible, accurate and reproducible
      method for evaluating MVP and chordae rupture in the clinical setting.

PMID- 21854427
TI  - Impaired aortic elastic properties in patients with chronic graft-versus-host
      disease.
AB  - OBJECTIVES: Graft-versus-host disease (GVHD), which develops as a result of the
      immunologic response that donor T-lymphocytes generate against host tissue
      following hematopoietic stem cell transplantation (HSCT), is the leading cause of
      morbidity and mortality in these patients. The aim of this study is the
      investigate relation between aortic wall stiffness and duration of the disease in
      patients with chronic GVHD. METHODS: The study population included 32 patients
      (18 men; mean age, 36.9+/-12.5 years, and mean disease duration=14.7+/-2.9
      months) who received HSCT and was diagnosed with GVHD and 44 patients (23 men;
      mean age, 35.2+/-9.6 years, and mean disease duration=13.5+/-2.4 months) who did
      not develop GVHD following HSCT. All patients underwent baseline echocardiography
      before HSCT and were followed. After approximately 10-14 months following HSCT,
      these patients were divided into two groups based on whether they had developed
      chronic GVHD, and were compared to aortic stiffness parameters and cardiac
      functions. RESULTS: There was no change in basal characteristics, laboratory and
      echocardiographic findings, and aortic stiffness parameters in both groups before
      HSCT (P>0.05). After HSCT, the mean aortic strain and distensibility values of
      the chronic GVHD patients were significantly lower, compared with the non-GVHD
      patients (9.8+/-3.2% vs. 12.9+/-5.0%, P=0.002 and 4.1+/-1.5*10(-6) cm2/dyn vs.
      5.3+/-2.1*10(-6) cm2/dyn; P=0.005, respectively). In addition, aortic stiffness
      index was increased in the chronic GVHD group compared with non-GVHD group (2.7+/
      1.7 vs. 2.0+/-0.8, P=0.03). CONCLUSION: Aortic stiffness measurements were
      significantly different in chronic GVHD group compared to non-GVHD group and
      these findings suggested useful explanation for the potential mechanism about the
      development of disease.

PMID- 21854428
TI  - Assessing global and regional left ventricular myocardial function in elderly
      patients using the bidimensional strain method.
AB  - Biological and anatomical alterations in the elderly result in modifications of
      the myocardial deformation detected previously by magnetic resonance imaging
      (MRI) technology and could have consequences on speckle tracking's parameters in
      this patient population. AIM: To compare left ventricular (LV) 2D strain between
      elderly patients and young individuals without heart disease. POPULATION AND
      METHODS: Patients without history of cardiac disease were enrolled from the
      geriatric department. After echocardiographic examination, exclusion criteria
      were LV myocardial abnormality, valve disease, and atrial fibrillation. The
      control group consisted of healthy subjects from the medical staff. 2D strain
      values were obtained from 16 segments in four-, three-, and two-chamber apical
      views for longitudinal and transversal strains, and from six basal segments in
      short-axis view for circumferential strain. RESULTS: Forty-five elderly patients
      (35 females) with mean age of 83.4+/-5.0 years (75-95 years) and 45 young
      subjects (28 females) with mean age of 33.6+/-7.5 years (17-45 years) were
      assessed. There was no difference between the two groups considering LV ejection
      fraction (66+/-6% vs. 65+/-4%, P=ns). Feasibility of segmental 2D strain was
      55.6% for circumferential strain, 63% for transversal strain, and 82% for
      longitudinal strain. Global longitudinal strain was significantly lower in
      elderly patients (-20.9+/-1.9% vs. -22.2+/-2.2%, P<0.01). There was no
      significant difference in global transversal and circumferential strain.
      CONCLUSION: Aging results in a decrease in global longitudinal strain. This
      should be taken into account in the assessment of pathological myocardial
      dysfunction.

PMID- 21854429
TI  - Quadricuspid aortic valve: a report of 12 cases and a review of the literature.
AB  - Quadricuspid aortic valve (QAV) is rare and its diagnosis, clinical course, and
      management are less well defined relative to other aortic valve abnormalities.
      Advances in diagnostic imaging, notably in ultrasound, have increased clinical
      awareness of this anomaly and prompted this review of our experience with 12 new
      patients and a compilation of previously reported patients to further
      characterize this condition.

PMID- 21854430
TI  - Hypereosinophilic syndrome presenting with large left ventricular apical thrombus
      and pulmonary embolism.
AB  - A 45-year-old man presented with dyspnea on exertion, fatigue, and cough.
      Transthoracic echocardiography showed a large apical thrombus in the left
      ventricle. The laboratory results showed prominent eosinophilia on blood smear,
      elevated acute phase reactants and D-dimer serum levels. Bone marrow examination
      showed a Fip1-like platelet-derived growth factor receptor alfa fusion gene
      mutation. The case was diagnosed as myeloproliferative variant hypereosinophilic
      syndrome. Contrast-enhanced computed tomography demonstrated thrombi not only in
      left ventricle but also in multiple segmental pulmonary arteries. Cardiac
      magnetic resonance imaging showed left ventricular apical thrombus without
      subendocardial fibrosis. Cardiopulmonary manifestations of hypereosinophilic
      syndrome completely resolved after treatment.

PMID- 21854431
TI  - Aortic atheromas: current knowledge and controversies: a brief review of the
      literature.
AB  - Atheromatous disease of the aorta is a known marker of vascular disease and is
      associated with ischemic stroke, peripheral embolization, and coronary events.
      Transesophageal echocardiogram is routinely used to assess aortic atheromas.
      Discrepancies exist in the grading of aortic atheromas. Atheromas with >4 mm
      thickness or with plaque rupture and mobile fragments are more likely to be
      associated with peripheral embolic events. Antiplatelet agents, oral
      anticoagulants, and statins have been suggested in the management of atheromas
      but sufficiently powered, randomized, controlled trials are not available to
      guide medical management of atheromas.

PMID- 21854432
TI  - Thrombosis of the LVAD inflow cannula detected by transthoracic echocardiography:
      2D and 3D thrombus visualization.

PMID- 21854433
TI  - Atropine augmentation of treadmill exercise stress echocardiography.
AB  - OBJECTIVES: Performance of exercise stress testing depends on adequate workload
      and is limited by patients' inability to reach target heart rate due to
      noncardiac illness or medications such as beta-blockers. This study aimed to
      assess the utility of atropine administration to augment the chronotropic
      response of patients undergoing treadmill exercise stress echocardiography.
      METHODS: In a retrospective study, we assessed the utility of atropine
      administration to augment the chronotropic response in 1,396 patients undergoing
      treadmill exercise stress echocardiography between January 2004 and January 2009,
      compared with a historical control group with no atropine augmentation. RESULTS:
      Atropine was well tolerated. The proportion of abnormal studies differed
      significantly between patients who underwent exercise with and without atropine
      augmentation (15% vs. 10%; P < 0.0001). Compared with the historical control
      group, the proportion of patients who achieved >=85% of their target heart rates
      increased from 67% to 78% (P < 0.0001). CONCLUSIONS: While atropine augmentation
      is safe and feasible, further studies are required to determine whether it is an
      equivalent surrogate to achieving target heart rate through exercise alone.

PMID- 21854434
TI  - Strain value in the assessment of left ventricular function and prediction of
      heart failure markers in aortic regurgitation.
AB  - BACKGROUND: This study aimed to examine the relationship between biochemical
      heart failure markers and conventional left ventricular (LV) measurements and
      strain assessed by speckle-tracking echocardiography in chronic aortic
      regurgitation (AR) patients. METHODS AND RESULTS: LV strain, rotation assessed by
      speckle-tracking echocardiography, LV measurements, mitral annular plane
      excursion measured by M-mode, and systolic annular plane velocity measured by
      tissue Doppler echocardiography were analyzed in 64 controls and 65 chronic AR
      patients. Reduced LV longitudinal strain with increased apical rotation was seen
      in normal plasma NT-proBNP patients. Increased NT-proBNP (>400 pg/mL) was
      associated with reduced longitudinal and circumferential strain, diminished
      mitral annular plane excursions and systolic annular plane velocity. Global
      systolic longitudinal strain was an indepentent predictor of NT-proBNP level.
      Longitudinal strain less than 16.0% was the cutoff value for NT-proBNP>400 pg/mL
      (P<0.05). CONCLUSIONS: LV strain analysis in conjunction with NT-proBNP
      evaluation is a useful tool in assessing LV function in AR patients.

PMID- 21854435
TI  - Endothelial-mediated coronary flow reserve and its relation to mitral annular
      tissue Doppler velocities in offspring of hypertensive parents.
AB  - BACKGROUND: Although coronary flow reserve (CFR) is reduced in hypertensive
      patients, data regarding the endothelial response of coronary vasomotion and its
      relation to left ventricular (LV) function in their offspring is limited.
      OBJECTIVE: To investigate the endothelial response of coronary flow, using cold
      pressor test (CPT), in offspring of hypertensive parents and its impact on LV
      diastolic function. SUBJECTS AND METHODS: The study population consisted of 32
      healthy young offspring (mean age 23.5 +/- 7.1 years) of hypertensive parents and
      26 aged matched volunteers (healthy offspring of normotensive parents) as
      controls. Coronary blood flow velocities were recorded in all subjects at rest
      and after CPT; a stimulus that can be considered totally endothelium-dependent.
      CFR was calculated as the ratio of hyperemic-to-resting diastolic peak
      velocities. Doppler echocardiographic assessment was performed using both
      conventional and tissue Doppler assessment. RESULTS: Coronary diastolic peak
      velocities at rest was comparable between the two groups (27.1 +/- 6.2 vs 26.4 +/
      5.8; P > 0.05); but the velocities were significantly lower after CPT in
      offspring of hypertensive parents (P < 0.02), with highly significant lower CFR
      (P < 0.0001). Conventional echo-Doppler variables were comparable in both groups,
      whereas tissue Doppler assessment demonstrated significant LV diastolic
      dysfunction among offspring of hypertensive parents. The CPT-CFR was
      significantly correlated to tissue Doppler diastolic dysfunction in this group
      (For Em, Am and Em/Am, r was 0.65, 0.59 and 0.61, respectively, and P < 0.001).
      CONCLUSION: Offspring of hypertensive parents have coronary endothelial
      dysfunction that appears in response to physiological stimuli (CPT). The coronary
      endothelial dysfunction is associated with latent LV diastolic dysfunction.

PMID- 21854436
TI  - Comparison study of echocardiography and dual-source CT in diagnosis of coronary
      artery aneurysm due to Kawasaki disease: coronary artery disease.
AB  - The identification of coronary artery aneurysm (CAA) in the acute and chronic
      phase of the disease is of prime importance for assessing the likelihood of acute
      lesions and cardiovascular sequelae. Occasionally, recognition of distal coronary
      artery has been proven challenging by traditional echocardiography. Our purpose
      was to evaluate the clinical application of two-dimensional echocardiography
      (2DE) for detecting CAA caused by Kawasaki disease (KD) and compare with dual
      source computed tomography (DSCT). A total of 24 patients with known KD and CAAs
      were studied by two imaging modalities, i.e., 2DE and DSCT; that is to say, the
      number, position, shape, and size of each CAA and its association with thrombus,
      were detected first from echocardiography and then compared with those obtained
      from DSCT performed on the same day. Meanwhile the diameters of all coronary
      segments were measured for each patient. Giant aneurysms (GAs) were detected in 5
      patients, small and medium coronary aneurysms were identified in 19 patients. The
      2DE and DSCT have the same results of proximal coronary artery, whereas
      conclusion of our comparison of coronary artery visualization indicated that DSCT
      provided more explicit distal coronary artery than 2DE. A mural thrombus could be
      clearly delineated in the GAs by DSCT. The 2DE has been demonstrated to be an
      accurate technique to quantify CAAs in KD. However, DSCT is superior to 2DE for
      distal coronary artery visualization. Therefore, a combination of
      echocardiography and DSCT can offer an overview of coronary artery anatomy.

PMID- 21854437
TI  - Two years of follow-up validates the echocardiographic criteria for the diagnosis
      and screening of rheumatic heart disease in asymptomatic populations.
AB  - OBJECTIVES: Out of 1,059 school children aged 6-15 years, screened 2 years ago,
      54 children were diagnosed with rheumatic heart disease (RHD) and put on
      penicillin prophylaxis. Significant regurgitation of mitral valves was detected
      in 39 cases of echocardiography diagnosed RHD, and in 15 cases significant
      regurgitation was detected to coexist with valve deformities. Three children had
      isolated mitral valve thickening without regurgitation. They were not given
      penicillin prophylaxis. These cases were followed up for 2 years. METHODS: After
      2 years, 54 children diagnosed with RHD and three children with isolated mitral
      valve thickening, were evaluated again. Lot quality assurance sampling was
      employed to screen a selected group of school children declared normal during the
      earlier evaluation. Lot was to be rejected, if, one child with significant
      regurgitation of mitral valve was found among the first 10 screened children of
      each of the 10 lots. FINDINGS: No lot was rejected and thus it was inferred that
      the prevalence of new onset RHD was negligible in the subset declared normal 2
      years ago. Isolated significant mitral regurgitation disappeared more often when
      present (35.9%) in comparison to when it (26.7%) was originally found coexistent
      with valve deformities. CONCLUSIONS: Highlight of the study is the greater
      reversibility of earlier lesions as compared to the later stages of RHD.
      Spontaneous regression of isolated mitral valve thickening in two-thirds of the
      cases even without antibiotic prophylaxis, undermines the value of morphological
      criteria for the diagnosis of RHD.

PMID- 21854438
TI  - Left atrial systolic force in asymptomatic aortic stenosis.
AB  - BACKGROUND: There is a limited knowledge about left atrial (LA) systolic force
      (LASF) and its key determinants in patients with asymptomatic mild-moderate
      aortic stenosis (AS). METHODS: We used baseline clinic and echocardiographic data
      from 1,566 patients recruited in the simvastatin ezetimibe in aortic stenosis
      study evaluating the effect of placebo-controlled combined simvastatin and
      ezetimibe treatment in asymptomatic AS. The LASF was calculated by Manning's
      method. Low and high LASF were defined as <5th and >95th percentile of the
      distribution within the study population, respectively. RESULTS: Mean LASF in the
      total study population was 21+/-14 kdynes/cm2. The determinants of LASF were
      higher age, heart rate, body mass index, systolic blood pressure, left
      ventricular (LV) mass, mitral peak early velocity, maximal LA volume, and longer
      mitral deceleration time (multiple R2=0.37, P<0.01). High LASF (78 patients) was
      characterized by abnormal LV relaxation in 90% of the cases. Low LASF (82
      patients) was associated with restrictive LV filling pattern, absence of abnormal
      relaxation pattern, smaller maximal LA volume, and lower body mass index. In 40%
      of the patients with low LASF, estimated LV filling pressures were normal and the
      reduced LA force was explainable by an intrinsic systolic LA dysfunction.
      CONCLUSIONS: In patients with asymptomatic AS, LASF was closely related to
      filling pressure. Higher LASF invariably signifies the maximal LA effort to keep
      near normal LV filling pressure; lower LASF belongs to a heterogeneous group of
      patients in which it is much more difficult to depict who have low LA preload or
      who have intrinsic systolic LA dysfunction.

PMID- 21854439
TI  - Prevalence of abnormal echocardiographic findings in cancer patients: a
      retrospective evaluation of echocardiography for identifying cardiac
      abnormalities in cancer patients.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) is commonly used to assess
      cardiac morphology and function in cancer patients. The nature, distribution, and
      prevalence of significant echocardiographic abnormalities are unknown. We
      hypothesized that TTEs performed for cancer or cancer treatment indications, have
      a high prevalence of significant abnormalities (SA), including a large proportion
      of findings that may be overlooked by other imaging modalities. METHODS: All TTE
      studies performed in a tertiary cancer center over a six-month period, from
      January to June 2007, were reviewed. The TTEs were divided into studies performed
      for a cardiovascular indication (CV) and those done for a cancer-related
      indication (CA). Reports were classified as normal, mildly abnormal, and
      significantly abnormal (SA) based on findings. Abnormal findings' distributions
      were compared between indication groups. RESULTS: Three thousand nine hundred and
      twenty-four TTEs were performed and divided into either group CV (61.2%) or group
      CA (38.7%). The most common indication in the CV group was valvular diseases
      (29.9%). In the CA group, the majority of TTE were requested for evaluation
      during or after chemotherapy or radiation (94.7%). Around 41.9% of studies in
      group CV were classified as SA whereas 19.9% (P < 0.001) in the CA group were
      classified as such. The relative distributions of individual SA findings were
      compared between the indication groups and were not statistically different.
      CONCLUSIONS: One in five patients who had TTE studies for CA were found to have
      SA, and 81.5% of these may not have been found with other modalities. The TTE
      allows safe diagnosis of a wide range of abnormal findings that may be overlooked
      if alternative but less versatile modalities are used.

PMID- 21854440
TI  - The predictive value of flow-mediated dilation and carotid artery intima-media
      thickness for occult coronary artery disease.
AB  - BACKGROUND: Multidetector row computed tomography (MDCT) is an attractive
      noninvasive alternative to assess overall coronary artery disease (CAD) burden
      and may reveal coronary plaques, which may be underestimated by conventional
      coronary angiography. The aim of this study was to determine whether brachial
      artery flow-mediated dilation (FMD) and carotid artery intima-media thickness
      (CIMT) might accurately predict patients with occult coronary plaques whose
      conventional coronary angiographies revealed normal coronary arteries (NCA).
      METHODS: Thirty-five patients with angiographically NCA were consecutively
      recruited into the study. They underwent MDCT and were divided into NCA group (18
      patients; 8 male; 47 +/- 9 years) and occult CAD group (17 patients; 11 male; 50
      +/- 10 years) according to presence of coronary plaque. Nineteen consecutive
      patients with evident CAD (16 male; 54 +/- 7 years) and 19 healthy subjects (10
      male; 50 +/- 6 years) were included as control groups. FMD and CIMT were measured
      by brachial and carotid artery ultrasonography. RESULTS: Occult CAD group had
      significantly lower FMD and insignificantly higher CIMT than NCA group whereas
      they had significantly higher FMD and insignificantly lower CIMT than evident CAD
      group. NCA group had significantly lower CIMT than evident CAD group. Receiver
      operating characteristic curve analysis demonstrated FMD < 8% (sensitivity:
      94.4%; specificity: 73.0%; PPV: 77.3%; NPV: 93.1%) and CIMT >= 0.65 cm
      (sensitivity: 72.2%; specificity: 62.2%; PPV: 65.0%; NPV: 69.7%) could predict
      patients with CAD. FMD and CIMT were independent predictors of CAD (P < 0.001;
      OR: 45.630; 95%CI: 5.38-386.983 and P = 0.015; OR: 14.226; 95%CI: 1.666-121.467,
      respectively). CONCLUSION: FMD and CIMT might predict patients with occult CAD
      and be helpful in selecting patients for MDCT.

PMID- 21854441
TI  - A warm footbath improves coronary flow reserve in patients with mild-to-moderate
      coronary artery disease.
AB  - BACKGROUNDS: Recent studies have shown that thermal therapy by means of warm
      waterbaths and sauna has beneficial effects in chronic heart failure. However, a
      comprehensive investigation of the hemodynamic effects of thermal vasodilation on
      coronary arteries has not been previously undertaken. In this study, we studied
      the effect of a warm footbath (WFB) on coronary arteries in patients with
      coronary artery disease (CAD), as well as any adverse effect. METHODS: We studied
      21 patients (33.3% men, mean age 60.8 +/- 13.5 years) with CAD. Coronary flow
      Doppler examination of the left anterior descending coronary artery and coronary
      flow reserve (CFR) were performed and measured using adenosine before and after a
      WFB. RESULTS: Systolic and diastolic blood pressure and heart rate did not change
      with the WFB. Mean velocity of diastolic coronary flow significantly increased
      (diastolic mean flow velocity: 18.3 +/- 7.1 cm/sec initial, 21.5 +/- 8.0 cm/sec
      follow-up, P = 0.002) and CFR significantly improved (1.6 +/- 0.4 vs. 2.2 +/-
      0.5, P < 0.001) after WFB. The WFB was well accepted and no relevant adverse
      effects were observed. The change of CFR after WFB correlated well with diastolic
      function (E', r = 0.51, P = 0.031; E/E', r =-0.675, P = 0.002). CONCLUSIONS: A
      WFB significantly improved CFR without any adverse effects in patients with mild
      to-moderate CAD and can be applied with little risk of a coronary artery event if
      appropriately performed.

PMID- 21854442
TI  - Echocardiography can be more sensitive than thoracic computed tomography in
      detecting a thrombus in the inflow cannula of a continuous left ventricular
      assist device.

PMID- 21854443
TI  - Malignant fibrous histiocytoma of the heart.

PMID- 21854444
TI  - Tissue Doppler derived mechanical dyssynchrony does not change after cardiac
      resynchronization therapy.
AB  - BACKGROUND: Mechanical left ventricular (LV) dyssynchrony, as determined by
      tissue Doppler imaging (TDI), predicts response to cardiac resynchronization
      therapy (CRT). However, changes in TDI mechanical dyssynchrony after CRT
      implantation have only limited investigation. Our objective was to detect changes
      in the extent and location of TDI mechanical dyssynchrony pre- and post-CRT, and
      to explore their relationship in response to CRT. METHODS: Thirty-nine
      consecutive patients undergoing CRT implantation for chronic heart failure
      underwent TDI analysis pre-CRT and up to 12 months post-CRT. Regional
      dyssynchrony was determined by the time to systolic peak velocity of opposing LV
      walls. Dyssynchrony was defined as a difference in time to peak contraction of
      >105 msec. Two patients were excluded, as suitable coronary venous access was not
      available. RESULTS: Of the 37 patients, 28 (76%) had significant mechanical
      dyssynchrony pre-CRT. Of those with dyssynchrony, 18 (64%) had septal delay and
      10 (36%) had LV free wall delay. Post-CRT, 29 (78%) patients had significant
      mechanical dyssynchrony, 17 (59%) with septal delay, and 12 (41%) with LV free
      wall delay. There was no difference in both the amount of dyssynchrony (P=0.8) or
      the location of the dyssynchrony (P=0.5), before and after CRT, even though 28
      (76%) were considered responders based on symptomatic and echocardiographic
      parameters. CONCLUSION: The TDI-derived dyssynchrony does not change with CRT
      despite significant symptomatic and echocardiographic improvement in cardiac
      function. The TDI is of limited utility for monitoring response to CRT.

PMID- 21854445
TI  - Beneficial effects of endogenous and exogenous melatonin on neural reconstruction
      and functional recovery in an animal model of spinal cord injury.
AB  - The purpose of this study was to investigate the beneficial effects of endogenous
      and exogenous melatonin on functional recovery in an animal model of spinal cord
      injury (SCI). Eight-week-old male Sprague-Dawley (SD, 250-260 g) rats were used
      for contusion SCI surgery. All experimental groups were maintained under one of
      the following conditions: 12/12-hr light/dark (L/D) or 24:0-hr constant light
      (LL). Melatonin (10 mg/kg) was injected subcutaneously for 4 wk, twice daily
      (07:00, 19:00). Locomotor recovery, inducible nitric oxide synthase (iNOS), glial
      fibrillary acidic protein gene expression, and muscle atrophy-related genes,
      including muscle atrophy F-box (MAFbx) and muscle-specific ring-finger protein 1
      (MuRF1) gene expression were evaluated. Furthermore, autophagic signaling such as
      Beclin-1 and LC3 protein expression was examined in the spinal cord and in
      skeletal muscle. The melatonin treatment resulted in increased hind-limb motor
      function and decreased iNOS mRNA expression in the L/D condition compared with
      the LL condition (P < 0.05), indicating that endogenous melatonin had
      neuroprotective effects. Furthermore, the MAFbx, MuRF1 mRNA level, and converted
      LC3 II protein expression were decreased in the melatonin-treated SCI groups
      under the LL (P < 0.05), possibly in response to the exogenous melatonin
      treatment. Therefore, it seems that both endogenous and exogenous melatonin
      contribute to neural recovery and to the prevention of skeletal muscle atrophy,
      promoting functional recovery after SCI. Finally, this study supports the benefit
      of endogenous melatonin and use of exogenous melatonin as a therapeutic
      intervention for SCI.

PMID- 21854446
TI  - Antidepressant-like effect of riparin II from Aniba riparia in mice: evidence for
      the involvement of the monoaminergic system.
AB  - In a previous study conducted by our group, riparin II (ripII) isolated from the
      green fruit of Aniba riparia presented antianxiety effects in mice. This study
      investigates a possible antidepressant activity of rip II using two predictive
      tests for antidepressant activity in rodents: the forced swimming test (FST) and
      tail suspension test (TST). Additionally, the mechanisms involved in the
      antidepressant-like effect in mice were also assessed. Rip II was acute
      administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at
      doses of 25 and 50 mg/kg. Results showed that ripII at both tested doses and
      administration routes produced a significant decrease of immobility time in FST
      and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an alpha1
      adrenoceptor antagonist), SCH23390 (15 MUg/kg, i.p., a dopamine D1 receptor
      antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p
      chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis), or NAN-190
      (0.5 mg/kg, a serotonin 5-HT1A receptor antagonist) completely blocked the anti
      immobility effects elicited by riparin II (50 mg/kg, p.o.) in the FST. This study
      indicates that riparin II produces significant antidepressant-like activity in
      the forced swimming and TSTs, and this effect seems to be dependent on its
      interaction with noradrenergic, dopaminergic, and serotonergic systems.

PMID- 21854447
TI  - Reduction in postnatal cumulative nutritional deficit and improvement of growth
      in extremely preterm infants.
AB  - AIM: To evaluate the influence of gestational age (GA) on cumulative nutritional
      deficit and postnatal growth in extremely preterm (EPT) infants after optimizing
      nutritional protocol as recently recommended. METHODS: A prospective,
      nonrandomized, observational study in extremely preterm (EPT, <28 weeks) and very
      preterm (VPT, 28-30 weeks) infants. RESULTS: Eighty-four infants were included
      (BW: 978 +/- 156 g, GA: 27.8 +/- 1.3 weeks). Cumulative nutritional deficit
      increased during first week of life to -290 +/- 84 and -285 +/- 117 kcal/kg and 
      4.2 +/- 3.1 and -4.8 +/- 3.9 g/kg of protein in EPT and VPT groups, respectively.
      After 6 weeks, only cumulative energy deficit in EPT group remained significant
      (p < 0.05) even when 96% of theoretical energy intakes were provided. Weight z
      score decreased during first 3 days in average with initial weight loss, and
      then, the z score increased during the first 6 weeks of life in the majority
      (75%) of infants. Cumulative protein deficit during the first week of life was
      the major determinant of the postnatal growth during the first 6 weeks of life.
      CONCLUSION: Cumulative nutritional deficit may be drastically reduced in both EPT
      and VPT infants after optimizing nutritional policy during the first weeks of
      life, and the postnatal growth restriction could even be prevented.

PMID- 21854448
TI  - The prevalence and risk factors of premature thelarche and pubarche in 4- to 8
      year-old girls.
AB  - AIM: To assess the prevalence of premature thelarche (PT) and pubarche in healthy
      4- to 8-year-old girls and to investigate factors associated with early pubertal
      development. METHOD: Eight hundred and twenty girls were examined by two
      paediatric endocrinologists to determine Tanner staging. The effects of body mass
      index, gestational age, intrauterine growth status, age at the first tooth
      eruption, socio-economical status, maternal age of menarche and consumption of
      certain food items on early pubertal development were analysed through parametric
      and nonparametric tests. RESULTS: The prevalence of PT and of premature pubarche
      was 8.9% and 4.3%, respectively. We found a strong association between the
      prevalence of PT and the body mass index standard deviation scores (BMI SDS).
      There were more girls with BMI SDS values above 1 in the PT group (56.1%) than
      among the remaining subjects (22.9%). Premature thelarche was not significantly
      associated with intrauterine growth, premature birth, socioeconomic status, age
      of first tooth eruption or maternal age of menarche. Similarly, the amount of
      milk, eggs, chicken or fish consumed was not associated with PT. None of the
      investigated factors were associated with premature pubarche. CONCLUSION:
      Occurrence of PT is strongly associated with BMI SDS. Studies investigating
      secular trends in pubertal development must consider a secular change in body
      mass index.

PMID- 21854449
TI  - On safety, pharmacokinetics and dosage of bevacizumab in ROP treatment - a
      review.
AB  - Off-label intravitreal use of the vascular endothelial growth factor (VEGF)
      antibody bevacizumab for retinopathy of prematurity (ROP) increases despite lack
      of studies on safety, pharmacokinetics and dosage in developing individuals.
      Systemic absorption has been considered negligible. A literature search was
      performed with emphasis on potential adverse systemic effects in developing
      individuals. CONCLUSION: Intravitreal bevacizumab enters the general circulation,
      suppresses plasma VEGF levels and remains in the blood for more than 8 weeks in
      primates. Possible adverse effects on VEGF-dependent development must be
      considered.

PMID- 21854450
TI  - 'Children are exposed to temptation all the time'- parents' lifestyle-related
      discussions in focus groups.
AB  - AIM: To explore parents' perspectives on providing their preschool child with a
      healthy lifestyle, including obstacles and resources. METHODS: Five semi
      structured focus group interviews were conducted, with 30 parents of 4-year-olds
      in Sweden. Interviews were transcribed verbatim and analysed using Systematic
      Text Condensation. RESULTS: Four themes emerged from the qualitative analysis:
      Lifestyle -'The way you live is parents' responsibility', Challenges to promote
      children's healthy lifestyle, Support from professionals, and peers might
      facilitate, and Request for an overall responsibility from society. Parents felt
      that they were role models for their child's lifestyle, a concept including many
      factors. Attractive and tempting sedentary activities and unhealthy foods were
      perceived as obstacles, and parents were frustrated by the media's contradictory
      lifestyle messages. Child health services were expected to more actively invite
      parents to discuss their child's lifestyle issues. Parents desired some
      collective responsibility for children's lifestyles through agencies, services
      and media messages that support and promote healthy choices. CONCLUSION: Parents
      struggled to give their children a healthy lifestyle and the 'temptations' of
      daily unhealthy choices causing hassles and conflicts. Parents desired
      professional support from preschool, Child Health Care and a collective
      responsibility from society with uniform guidelines. Parents groups were
      mentioned as peer support.

PMID- 21854451
TI  - Calcium supplements lower bone resorption after renal transplant.
AB  - AIM: Bone loss in renal transplant (RT) patients is a problem that begins during
      end-stage kidney disease and persists after transplantation. Suppression of
      parathyroid hormone (PTH) may decrease bone loss and improve fracture rate.
      METHODS: A single-group prospective intervention study involving 30 patients was
      performed at a large RT unit. Investigations included dual-emission X-ray
      absorptiometry scan, vertebral X-ray, calcium absorption test, 24-h urinary
      calcium and serum measurements of total and ionized calcium, PTH, C-telopeptide
      cross-links (CTX), osteocalcin, alkaline phosphatase, 25 hydroxyvitamin D
      (25[OH]D), and 1,25-dihydroxyvitamin D3. Patients were given 500 mg elemental
      calcium daily for seven d, and serum measurements were repeated. RESULTS: Two
      tailed Wilcoxon rank-sum test showed significant decreases in PTH (p<0.01) and
      CTX (p<0.01) after calcium load. Dietary calcium, mean calcium absorption, and
      urinary calcium excretion were below desirable levels. Mean 25 hydroxyvitamin D
      (25(OH)D) was low, but levels of 1,25-dihydroxyvitamin D3 were normal. Calcium
      absorption significantly correlated with change in PTH (p<0.001), baseline
      25(OH)D (p<0.001), and mycophenolate dose (p=0.024). CONCLUSIONS: Calcium
      malabsorption is prevalent in RT recipients, contributing to bone destruction and
      compounded by poor dietary intake and low 25(OH)D. Calcium supplementation
      appears to help overcome this deficiency and acutely suppress PTH. Calcium may be
      an effective and inexpensive therapy for bone loss in RT recipients.

PMID- 21854452
TI  - Prevalence and risk factors of polyomavirus BK replication in simultaneous
      pancreas/kidney transplant recipients from a single transplant center.
AB  - BACKGROUND: BK virus (BKV) replication is considered as a marker of risk for
      polyomavirus BK-associated nephropathy (PVAN). We evaluated the occurrence and
      risk factors for BKV DNA positivity following simultaneous pancreas/kidney
      transplantation (SPK). METHODS: Point prevalence of BK viruria and viremia was
      assessed in 183 SPK recipients. Real-time polymerase chain reaction was used with
      a detection threshold of 10(3) copies/mL. High-level BKV positivity was defined
      as viruria and/or viremia >10(7) and >10(4) copies/mL, respectively. BKV-positive
      patients were retested after 4-13 months and underwent an additional six-month
      clinical follow-up. RESULTS: Urine and serum BKV positivity was detected in 28
      (17.3% of available samples) and 7 (3.8%) patients, with high-level viruria and
      viremia occurring in 6 (3.7%) and 3 (1.6%) patients, respectively. PVAN was
      biopsy-confirmed in 1 and suspected as a cause of progressive renal failure in
      another SPK recipient. Patients with single low-level viruria did not progress to
      high-level positivity or PVAN at follow-up. In multivariate analysis, pre
      transplant diabetes duration and delayed graft function were independently
      associated with BKV positivity. CONCLUSIONS: Point prevalence of high-level BKV
      positivity and PVAN was low in SPK recipients from a single center. Diabetes
      duration and delayed graft function were independent risk factors for BKV
      replication.

PMID- 21854453
TI  - Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences
      methotrexate/6-mercaptopurine dosing but not event-free survival for childhood
      acute lymphoblastic leukemia.
AB  - Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute
      lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored
      to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP)
      dosage, myelosuppression, and event-free survival (EFS) during maintenance
      therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients
      received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never
      received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed
      PCP, eight of which occurred within 7 months from the start of maintenance
      therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never)
      patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil
      counts (ANC) (median 1.7 vs. 2.0 * 10(9) /L; P<0.001). In Cox multivariate
      analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to
      reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but
      did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS
      between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46).
      EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs.
      0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP
      and may have an antileukemic effect. TMP/SMX should be given the entire duration
      of maintenance therapy.

PMID- 21854454
TI  - Living donor liver transplantation for hepatocellular carcinoma: a single center
      analysis of outcomes and impact of different selection criteria.
AB  - We examined the outcomes of patients who received living donor liver
      transplantation (LDLT) for HCC comparing the impact of up-to-seven criteria and
      Asan Criteria (AC) with Milan Criteria (MC). Between July 2004 and July 2009, of
      175 consecutive LDLT, there were 45 consecutive patients with HCC. Forty patients
      who completed 12 months follow-up were enrolled. In search for the highest number
      of expansion, we selected AC as the extended criteria. Patients were divided into
      having tumors within MC, beyond MC within AC and Beyond Criteria (BC) groups.
      With a median follow-up of 46 months, overall 1, 3, and 5 years survival was 
      90%, -81%, and -70%, respectively. In patients within AC, estimated mean survival
      was 49.8 vs. 40.5 months for BC group (P = 0.2). Disease-free survival was
      significantly higher in patients within AC comparing with BC group; 48.0 vs. 38.6
      months (P = 0.04). Preoperative AFP level >400 and poor tumor differentiation
      were factors adversely effecting recipient survival. On multivariate analysis,
      the presence of poor tumor differentiation (P = 0.018 RR: 2.48) was the only
      independent predictor of survival. Extension of tumor size and number to AC is
      feasible, without significantly compromising outcomes; however, the presence of
      poor tumor differentiation was associated with worse outcomes after LDLT.

PMID- 21854456
TI  - New challenges in the analysis of gene transcription in bovine blastocysts.
AB  - In the last years, enormous progress has been made in the analysis of gene
      transcription at the blastocyst stage. The study of gene expression at this early
      stage of development is challenging because of the very small amount of starting
      material, which limits the use of traditional mRNA analysis approaches such as
      Northern blot. Another problem is the difficulty for data normalization,
      particularly the identification of the best housekeeping gene with the lowest
      fluctuation under different developmental conditions. Moreover, the
      transcriptional analysis of embryo biopsies or individual embryos needs to take
      into consideration that the blastocyst is a transitional stage of development,
      which is composed of three different types of cells (trophoblast, epiblast and
      primitive ectoderm) with different patterns of gene expression, and that there
      are large differences between male and female blastocysts. In this review, we
      analyse the different specific and sensitive tools available to compare mRNA
      expression levels of specific genes at the blastocyst stage, and how the protocol
      and the analytical method used can influence the results dramatically. Finally,
      we describe future research challenges to identify candidate genes related to
      developmental competence of bovine blastocysts, not only in terms of pregnancy
      rates but also in relation to adverse long-term consequences in the adult animal.

PMID- 21854457
TI  - Dry period management and optimization of post-partum reproductive management in
      dairy cattle.
AB  - Dry period and early post-partum management are decisive factors for fertility in
      lactating dairy cows. Previous studies have shown that decreased dry matter
      intake (DMI) and increased non-esterified fatty acids (NEFA) negatively affect
      fertility and subsequent milk production. The traditional dry period decreases
      DMI prior to parturition, resulting in a decrease in energy intake. A negative
      energy balance increases NEFA concentration, and increased NEFA may impair the
      immune system, especially by decreasing neutrophil function prior to parturition.
      Earlier studies have shown that post-partum health disorders, including retained
      placenta and metritis, were correlated with periparturient neutrophil function.
      In addition, decreased DMI is also linked to a reduced body condition score (BCS)
      in dairy cows. These events in the periparturient period negatively affect
      fertility. Some manipulation, such as shortening the dry period, may be a
      solution to increased DMI in the periparturient period, preventing post-partum
      disorders and subsequent fertility issues. This article aims to explain the
      effects of shortening the dry period on reproduction and early post-partum
      treatments to improve fertility. In addition, timed artificial insemination
      protocols will be discussed for use during the post-partum period to improve
      fertility in dairy cows.

PMID- 21854458
TI  - The immunology of early pregnancy in farm animals.
AB  - The mammalian conceptus undergoes development in the face of a functional immune
      system. This characteristic of viviparity creates opportunities and perils for
      the conceptus. In the period up to hatching from the zona pellucida, the
      conceptus appears immunologically inert with low expression of major
      histocompatibility complex (MHC) genes and little evidence for alterations in the
      function of maternal immune cells. The conceptus may benefit from cytokines
      produced by leucocytes resident in the reproductive tract or by other cells of
      the reproductive tract. One cytokine in particular, colony-stimulating factor 2,
      can promote preimplantation development and cause changes in conceptus function
      that increase the likelihood that the conceptus develops to term. It is not clear
      whether activation of specific types of immune responses in early pregnancy can
      enhance the likelihood of pregnancy success. Semen deposition causes inflammation
      in the reproductive tract, but there is little evidence that this process is
      beneficial to pregnancy unless the uterus was exposed to a prior inflammatory
      event. Around the time of placentation, the period of immunological inertness of
      the conceptus is replaced by a period of immune activation caused by the
      expression of interferon genes in ruminants and pigs and MHC class I genes in
      invasive trophoblast of the horse. The large-scale changes in the endometrium
      that occur as a result are likely to play an important role to ensure continued
      development of the conceptus. In contrast, other immune responses generated as a
      result of disease in the reproductive tract or other tissues (mastitis) can lead
      to death of the conceptus. Because of this hazard, as well as the possibility
      that cell-mediated immune responses against the conceptus could occur, the immune
      system is regulated by both the mother and conceptus to reduce immune
      responsiveness during pregnancy.

PMID- 21854459
TI  - Mechanisms for the establishment of pregnancy in the pig.
AB  - Establishment of pregnancy in pigs requires continuous function of corpora lutea
      and endometrial preparation for embryo implantation. Progesterone regulates
      expression of many proteins necessary for endometrial remodelling and embryo
      maternal communications. Attaining the uterine receptivity involves progesterone
      priming and loss of progesterone receptors in the uterine epithelium before days
      10-12 after oestrus. Spermatozoa and oocytes in oviduct alter secretion of
      specific proteins that exert beneficial effect on gametes and embryos. Moreover,
      an appropriate leucocyte activation and maintenance of delicate cytokine balance
      within the oviduct and uterus are important for early pregnancy. This early local
      immune response is rather mediated by seminal plasma components. These components
      also influence prostaglandin (PG) synthesis in the oviduct that is important for
      gamete and embryo transport. Pregnancy establishment requires the biphasic
      pattern of oestrogen secretion by conceptuses on days 11-12 and 15-30. Conceptus
      affects lipid signalling system consisting of prostaglandins and lysophosphatic
      acid. PG synthesis is changed by conceptus signals in favour of luteoprotective
      PGE(2) . Additionally, existence of PGE(2) positive feedback loop in the
      endometrium contributes to increased PGE(2) /PGF(2alpha) ratio during the peri
      implantation period. PGE(2) through endometrial PGE(2) receptor (PTGER2) elevates
      the expression of enzymes involved in PGE(2) synthesis. Higher PGE(2) secretion
      in uterine lumen coincides with the elevated expression of HOXA10 transcription
      factor critical for implantation. A stable adhesion between conceptus and
      endometrium requires reduction in mucin-1 on the apical surface of epithelium and
      integrin activation by extracellular matrix proteins. Furthermore, growth
      factors, cytokines and its receptors are involved in embryo-maternal
      interactions.

PMID- 21854460
TI  - Golden perspective: application of laser-generated gold nanoparticle conjugates
      in reproductive biology.
AB  - The current demand for female calves has grown rapidly and controlling the sex of
      offspring provides an economically flexible management for the livestock
      producer. The only functioning method of efficiently producing separate
      populations of X and Y sperm in mammals is based on relative DNA differentiation
      by high-speed flow cytometry. In this context, gold nanoparticles conjugated to
      sex chromosome-specific moieties display promising application as novel
      fluorophor-alternative for the high-throughput screening, since they feature no
      photo bleaching, high quantum yield, good biocompatibility and the possibility of
      non-destructive membrane penetration. Especially, gold nanoparticles fabricated
      by pulsed laser ablation are in the recent focus of interest, due to excellent
      biocompatibility, fabrication-dependent, tuneable particle size as well as
      surface charge and ease of (bio)-functionalization with a remarkably strong
      ligand binding. For the purpose of our studies functionalized gold nanoparticles
      may be used as novel markers for sex-sorting of mammalian sperm and, depending on
      the selected probe, also for the selection of sperm with heritable DNA-sequences
      interesting for animal breeding.

PMID- 21854462
TI  - Inactivation of a novel response regulator is necessary for biofilm formation and
      host colonization by Vibrio fischeri.
AB  - The marine bacterium Vibrio fischeri uses a biofilm to promote colonization of
      its eukaryotic host Euprymna scolopes. This biofilm depends on the symbiosis
      polysaccharide (syp) locus, which is transcriptionally regulated by the RscS-SypG
      two-component regulatory system. An additional response regulator (RR), SypE,
      exerts both positive and negative control over biofilm formation. SypE is a novel
      RR protein, with its three putative domains arranged in a unique configuration: a
      central phosphorylation receiver (REC) domain flanked by two effector domains
      with putative enzymatic activities (serine kinase and serine phosphatase). To
      determine how SypE regulates biofilm formation and host colonization, we
      generated a library of SypE domain mutants. Our results indicate that the N
      terminus inhibits biofilm formation, while the C-terminus plays a positive role.
      The phosphorylation state of SypE appears to regulate these opposing activities,
      as disruption of the putative site of phosphorylation results in a protein that
      constitutively inhibits biofilm formation. Furthermore, SypE restricts host
      colonization: (i) sypE mutants with constitutive inhibitory activity fail to
      efficiently initiate host colonization and (ii) loss of sypE partially alleviates
      the colonization defect of an rscS mutant. We conclude that SypE must be
      inactivated to promote symbiotic colonization by V. fischeri.

PMID- 21854464
TI  - The superoxide dismutase SodA is targeted to the periplasm in a SecA-dependent
      manner by a novel mechanism.
AB  - The manganese/iron-type superoxide dismutase (SodA) of Rhizobium leguminosarum
      bv. viciae 3841 is exported to the periplasm of R. l. bv. viciae and Escherichia
      coli. However, it does not possess a hydrophobic cleaved N-terminal signal
      peptide typically present in soluble proteins exported by the Sec-dependent (Sec)
      pathway or the twin-arginine translocation (TAT) pathway. A tatC mutant of R. l.
      bv. viciae exported SodA to the periplasm, ruling out export of SodA as a complex
      with a TAT substrate as a chaperone. The export of SodA was unaffected in a secB
      mutant of E. coli, but its export from R. l. bv. viciae was inhibited by azide,
      an inhibitor of SecA ATPase activity. A temperature-sensitive secA mutant of E.
      coli was strongly reduced for SodA export. The 10 N-terminal amino acid residues
      of SodA were sufficient to target the reporter protein alkaline phosphatase to
      the periplasm. Our results demonstrate the export of a protein lacking a
      classical signal peptide to the periplasm by a SecA-dependent, but SecB
      independent targeting mechanism. Export of the R. l. bv. viciae SodA to the
      periplasm was not limited to the genus Rhizobium, but was also observed in other
      proteobacteria.

PMID- 21854463
TI  - Bioluminescent imaging of Borrelia burgdorferi in vivo demonstrates that the
      fibronectin-binding protein BBK32 is required for optimal infectivity.
AB  - The aetiological agent of Lyme disease, Borrelia burgdorferi, is transmitted via
      infected Ixodes spp. ticks. Infection, if untreated, results in dissemination to
      multiple tissues and significant morbidity. Recent developments in
      bioluminescence technology allow in vivo imaging and quantification of pathogenic
      organisms during infection. Herein, luciferase-expressing B. burgdorferi and
      strains lacking the decorin adhesins DbpA and DbpB, as well as the fibronectin
      adhesin BBK32, were quantified by bioluminescent imaging to further evaluate
      their pathogenic potential in infected mice. Quantification of bacterial load was
      verified by quantitative PCR (qPCR) and cultivation. B. burgdorferi lacking DbpA
      and DbpB were only seen at the 1 h time point post infection, consistent with its
      low infectivity phenotype. The bbk32 mutant exhibited a significant decrease in
      its infectious load at day 7 relative to its parent. This effect was most
      pronounced at lower inocula and imaging correlated well with qPCR data. These
      data suggest that BBK32-mediated binding plays an important role in B.
      burgdorferi colonization. As such, in vivo imaging of bioluminescent Borrelia
      provides a sensitive means to detect, quantify and temporally characterize
      borrelial dissemination in a non-invasive, physiologically relevant environment
      and, more importantly, demonstrated a quantifiable infectivity defect for the
      bbk32 mutant.

PMID- 21854466
TI  - Cleavage oxygenases for the biosynthesis of trisporoids and other apocarotenoids
      in Phycomyces.
AB  - Mixed cultures of strains of opposite sex of the Mucorales produce trisporic
      acids and other compounds arising from cleavage of beta-carotene, some of which
      act as signals in the mating process. The genome of Phycomyces blakesleeanus
      contains five sequences akin to those of verified carotenoid cleavage oxygenases.
      All five are transcribed, three of them have the sequence traits that are
      considered essential for activity, and we have discovered the reactions catalysed
      by the products of two of them, genes carS and acaA. The transcripts of carS
      became more abundant in the course of mating, and its expression in beta-carotene
      producing Escherichia coli cells led to the formation of beta-apo-12'-carotenal,
      a C25 cleavage product of beta-carotene. Joint expression of both genes in the
      same in vivo system resulted in the production of beta-apo-13-carotenone, a C18
      fragment. In vitro, AcaA cleaved beta-apo-12'-carotenal into beta-apo-13
      carotenone and was active on other apocarotenoid substrates. According to these
      and other results, the first reactions in the apocarotenoid pathway of Phycomyces
      are the cleavage of beta-carotene at its C11'-C12' double bond by CarS and the
      cleavage of the resulting C25-fragment at its C13-14 double bond by AcaA.

PMID- 21854465
TI  - The broadly conserved regulator PhoP links pathogen virulence and membrane
      potential in Escherichia coli.
AB  - PhoP is considered a virulence regulator despite being conserved in both
      pathogenic and non-pathogenic Enterobacteriaceae. While Escherichia coli strains
      represent non-pathogenic commensal isolates and numerous virulent pathotypes, the
      PhoP virulence regulator has only been studied in commensal E. coli. To better
      understand how conserved transcription factors contribute to virulence, we
      characterized PhoP in pathogenic E. coli. Deletion of phoP significantly
      attenuated E. coli during extraintestinal infection. This was not surprising
      since we demonstrated that PhoP differentially regulated the transcription of >
      600 genes. In addition to survival at acidic pH and resistance to polymyxin, PhoP
      was required for repression of motility and oxygen-independent changes in the
      expression of primary dehydrogenase and terminal reductase respiratory chain
      components. All phenotypes have in common a reliance on an energized membrane.
      Thus, we hypothesized that PhoP mediates these effects by regulating genes
      encoding proteins that generate proton motive force. Indeed, bacteria lacking
      PhoP exhibited a hyperpolarized membrane and dissipation of the transmembrane
      electrochemical gradient increased susceptibility of the phoP mutant to acidic
      pH, while inhibiting respiratory generation of the proton gradient restored
      resistance to antimicrobial peptides independent of lipopolysaccharide
      modification. These findings demonstrate a connection between PhoP, virulence and
      the energized state of the membrane.

PMID- 21854467
TI  - Two internal type II NADH dehydrogenases of Toxoplasma gondii are both required
      for optimal tachyzoite growth.
AB  - In many apicomplexan parasites the entry of electrons from NADH into the electron
      transport chain is governed by type II NADH dehydrogenases (NDH2s) instead of a
      canonical complex I. Toxoplasma gondii expresses two NDH2 isoforms, TgNDH2-I and
      TgNDH2-II with no indication for stage-specific regulation. We dissected the
      orientation of both isoforms by using a split GFP assay and a protease protection
      assay after selective membrane permeabilization. The two approaches revealed that
      both TgNDH2 isoforms are internal enzymes facing with their active sites to the
      mitochondrial matrix. Single knockout mutants displayed a decreased replication
      rate and a reduced mitochondrial membrane potential, which were both more severe
      in the Tgndh2-II-deleted than in the Tgndh2-I-deleted mutant. Complementation
      with a myc-tagged, ectopic copy of the deleted gene restored the growth rate and
      the mitochondrial membrane potential. However, an overexpression of the remaining
      intact isoform could not restore the phenotype, suggesting that the two TgNDH2
      isoforms are non-redundant and possess functional differences. Together, our
      studies indicate that although TgNDH2-I and TgNDH2-II are individually non
      essential, the expression of both internal isoforms is required to maintain the
      mitochondrial physiology in T. gondii tachyzoites.

PMID- 21854468
TI  - The NAD+ metabolism of Leishmania, notably the enzyme nicotinamidase involved in
      NAD+ salvage, offers prospects for development of anti-parasite chemotherapy.
AB  - NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox
      reactions it is key in the cellular energy metabolism and as a substrate it
      participates in many reactions leading to a variety of covalent modifications of
      enzymes with major roles in regulation of expression and metabolism. Cells may
      have the ability to produce this metabolite either via alternative de novo
      synthesis pathways and/or by different salvage pathways. In this issue of
      Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania
      species can only rely on the salvage of NAD+ building blocks. One of the enzymes
      involved, nicotinamidase, is absent from human cells. The enzyme is important for
      growth of Leishmania infantum and essential for establishing an infection. The
      crystal structure of the parasite protein has been solved and shows prospects for
      design of inhibitors to be used as leads for development of new drugs. Indeed,
      NAD+ metabolism is currently being considered as a promising drug target in
      various diseases and the vulnerability of Leishmania for interference of this
      metabolism has been proved in previous work by the same group, by showing that
      administration of NAD+ precursors has detrimental effect on the pathogenic,
      amastigote stage of this parasite.

PMID- 21854470
TI  - Ganglioneuroma in the neck masquerading as a benign mesenchymal lesion on
      cytology: a morphological mimic.

PMID- 21854469
TI  - Substitutions in the redox-sensing PAS domain of the NifL regulatory protein
      define an inter-subunit pathway for redox signal transmission.
AB  - The Per-ARNT-Sim (PAS) domain is a conserved alpha/beta fold present within a
      plethora of signalling proteins from all kingdoms of life. PAS domains are often
      dimeric and act as versatile sensory and interaction modules to propagate
      environmental signals to effector domains. The NifL regulatory protein from
      Azotobacter vinelandii senses the oxygen status of the cell via an FAD cofactor
      accommodated within the first of two amino-terminal tandem PAS domains, termed
      PAS1 and PAS2. The redox signal perceived at PAS1 is relayed to PAS2 resulting in
      conformational reorganization of NifL and consequent inhibition of NifA activity.
      We have identified mutations in the cofactor-binding cavity of PAS1 that prevent
      'release' of the inhibitory signal upon oxidation of FAD. Substitutions of
      conserved beta-sheet residues on the distal surface of the FAD-binding cavity
      trap PAS1 in the inhibitory signalling state, irrespective of the redox state of
      the FAD group. In contrast, substitutions within the flanking A'alpha-helix that
      comprises part of the dimerization interface of PAS1 prevent transmission of the
      inhibitory signal. Taken together, these results suggest an inter-subunit pathway
      for redox signal transmission from PAS1 that propagates from core to the surface
      in a conformation-dependent manner requiring a flexible dimer interface.

PMID- 21854471
TI  - Hyperhaemolysis syndrome treated with corticosteroids and darbopoietin in a
      patient with mantle cell lymphoma.

PMID- 21854472
TI  - Job satisfaction and intention to leave: a questionnaire survey of hospital
      nurses in Shanghai of China.
AB  - AIM: To explore nurses' views and experiences regarding job satisfaction and
      their intention to leave in Shanghai. BACKGROUND: The widespread nursing shortage
      and nurses' high turnover rate has become a global issue. Job satisfaction is the
      most consistent predictor of nurses' intention to leave and has been reported as
      explaining most of the variance on their intention to leave. DESIGN: A cross
      sectional survey. METHODS: A convenience sample of nurses was recruited from 19
      large general hospitals in Shanghai and the research assistants distributed 2850
      questionnaires to nurses. The response rate of this study was 78.95%, and 2250
      nurses completed the questionnaire. RESULTS: Regarding the overall job
      satisfaction, 50.2% nurses were dissatisfied and 40.4% nurses reported that they
      had intention to leave the current employment. Respondents' characteristics had
      an impact on job satisfaction and their intention to leave. The results showed
      that age, marital status, work experience, overall job satisfaction, job
      satisfaction: extrinsic rewards, interaction, praise/recognition and
      control/responsibility were significant factors contributing to nurses' intention
      to leave. CONCLUSIONS: The finding may be a cause of concern for hospital
      management and highlights the importance of the two concepts (job satisfaction
      and intention to leave) in Shanghai. Innovative and adaptable managerial
      interventions need to be taken to improve nurses' job satisfaction and to
      strengthen their intention to stay. RELEVANCE TO CLINICAL PRACTICE: Our findings
      outline some issues contributing to these problems and provide nurse
      administrators with information regarding specific influences on nurses' job
      satisfaction and intention to leave in Shanghai and innovative and adaptable
      managerial interventions that are needed. Our findings may also provide direction
      for nurse managers and healthcare management to implement strategies to improve
      nurses' job satisfaction and their intention to stay.

PMID- 21854473
TI  - Identifying key performance indicators for nursing and midwifery care using a
      consensus approach.
AB  - AIMS: The aim of this study was to gain consensus on key performance indicators
      that are appropriate and relevant for nursing and midwifery practice in the
      current policy context. BACKGROUND: There is continuing demand to demonstrate
      effectiveness and efficiency in health and social care and to communicate this at
      boardroom level. Whilst there is substantial literature on the use of clinical
      indicators and nursing metrics, there is less evidence relating to indicators
      that reflect the patient experience. DESIGN: A consensus approach was used to
      identify relevant key performance indicators. METHODS: A nominal group technique
      was used comprising two stages: a workshop involving all grades of nursing and
      midwifery staff in two HSC trusts in Northern Ireland (n = 50); followed by a
      regional Consensus Conference (n = 80). During the workshop, potential key
      performance indicators were identified. This was used as the basis for the
      Consensus Conference, which involved two rounds of consensus. Analysis was based
      on aggregated scores that were then ranked. RESULTS: Stage one identified 38
      potential indicators and stage two prioritised the eight top-ranked indicators as
      a core set for nursing and midwifery. The relevance and appropriateness of these
      indicators were confirmed with nurses and midwives working in a range of settings
      and from the perspective of service users. CONCLUSIONS: The eight indicators
      identified do not conform to the majority of other nursing metrics generally
      reported in the literature. Furthermore, they are strategically aligned to work
      on the patient experience and are reflective of the fundamentals of nursing and
      midwifery practice, with the focus on person-centred care. RELEVANCE TO CLINICAL
      PRACTICE: Nurses and midwives have a significant contribution to make in
      determining the extent to which these indicators are achieved in practice.
      Furthermore, measurement of such indicators provides an opportunity to evidence
      of the unique impact of nursing/midwifery care on the patient experience.

PMID- 21854474
TI  - A pressure ulcer prevention programme specially designed for nursing homes: does
      it work?
AB  - AIM: The aim of this study was to evaluate a pressure ulcer prevention programme
      for nursing homes to ascertain the feasibility of its implementation, impact on
      care staff and outcomes for pressure ulcer knowledge and skills and pressure
      ulcer reduction. BACKGROUND: No pressure ulcer prevention protocol for long-term
      care settings has been established to date. The first author of this study thus
      developed a pressure ulcer prevention programme for nursing homes. DESIGN: A
      quasi-experimental pretest and post-test design was adopted. METHODS: Forty-one
      non-licensed care providers and eleven nurses from a government-subsidised
      nursing home voluntarily participated in the study. Knowledge and skills of the
      non-licensed care providers were assessed before, immediately after and six weeks
      after the training course, and pressure ulcer prevalence and incidence were
      recorded before and during the protocol implementation. At the end of the
      programme implementation, focus group interviews with the subjects were conducted
      to explore their views on the programme. RESULTS: A statistically significant
      improvement in knowledge and skills scores amongst non-licensed care providers
      was noted. Pressure ulcer prevalence and incidence rates dropped from 9-2.5% and
      2.5-0.8%, respectively, after programme implementation. The focus group findings
      indicated that the programme enhanced the motivation of non-licensed care
      providers to improve their performance of pressure ulcer prevention care and
      increased communication and cooperation amongst care staff, but use of the
      modified Braden scale was considered by nurses to increase their workload.
      CONCLUSION: A pressure ulcer prevention programme for nursing homes, which was
      feasible and acceptable, with positive impact and outcome in a nursing home was
      empirically developed. RELEVANCE TO CLINICAL PRACTICE: The study findings can be
      employed to modify the programme and its outcomes for an evaluation of
      effectiveness of the programme through a randomised controlled trial.

PMID- 21854477
TI  - 37-year-old woman with multiple intracranial masses.
AB  - Extramedullary hematopoiesis (EMH), defined as the presence of hematopoiesis
      outside bone marrow and peripheral blood, occurs asa compensatory phenomenon in
      several hematologic disorders and bone marrow dysfunction. EMH predominantly
      affects reticuloendothelial system including the spleen, liver and lymph nodes.
      Here,we report a rare case of multiple intracranial meningeal EMH. A37-year-old
      woman was anemic with gradually worsening vision for 8 months. Multiple extra
      axial masses were found on imaging and the patient underwent the biopsy for the
      left frontotemporal lesion.Final diagnosis was multiple intracranial meningeal
      EMH. Treatment of fractionated external beam radiotherapy resulted in marked
      symptomatic improvement. This case indicates that although the diagnosis of
      meningeal EMH is difficult, there is a need to consider EMHin the differential
      diagnosis of anemic patients with tumor-like mass lesions in extramedullary
      sites.

PMID- 21854478
TI  - A progressive multifocal neurological syndrome in a 42-year-old woman.
AB  - This is the case of a 42-year-old female who presented with transient dizziness.
      Her symptoms and signs progressed to include dysarthria, ataxia and cognitive
      decline over 2 years, such that she was unable to care for herself. She died 4
      years after first presentation without a diagnosis. Investigations revealed a
      normochromic normocytic anaemia. Cerebrospinal fluid was normal. Serial computed
      tomography brain showed a wedge-shaped frontal infarct but no progressive
      changes. Examination at autopsy showed discoloration of the gray and white matter
      of the brain and spinal cord.Microscopy of leptomeningeal and parenchymal vessels
      showed they were filled with atypical B lymphocytes confined to the intravascular
      space with multiple infarcts in the brain, cerebellum and spinal cord. A
      diagnosis of intravascular B cell lymphoma was made and is discussed.

PMID- 21854479
TI  - Approaches to normalization of spinal cord volume: application to multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: To determine the proper method for the normalization of
      spinal cord volume. MATERIALS AND METHODS: A group of 34 multiple sclerosis (MS)
      patients (28 relapsing and 6 progressive) and 15 healthy controls had whole
      spinal cord 3-mm thick T2-weighted axial fast spin-echo magnetic resonance
      imaging (MRI) images obtained at 3T. For each participant, four volumes were
      measured (C2-3 volume, cervical cord volume, thoracic cord volume, and whole cord
      volume). The volumes were normalized by the number of slices and three potential
      measures of body size (intracranial volume [ICV], body mass index, and body
      surface area) using the proportional method. RESULTS: All raw volumes and volumes
      normalized by number of slices or ICV were significantly lower in progressive MS
      patients compared to relapsing MS patients/healthy controls (P < .05). In
      addition, C2-3 volume and cervical cord volume were significantly correlated with
      Expanded Disability Status Scale score (P < .05). All regional volumes showed
      high intercorrelation, and normalization by the number of slices significantly
      increased some correlations. Regarding reliability, whole cord volume regardless
      of normalization technique had lower coefficient of variation than C2-3 volume.
      CONCLUSIONS: Since normalization factor had limited impact on reliability and the
      ability to detect differences, normalization by the number of slices is
      recommended.

PMID- 21854480
TI  - Comparing National Institutes of Health funding of emergency medicine to four
      medical specialties.
AB  - OBJECTIVES: The purpose of this study was to compare National Institutes of
      Health (NIH) funding received in 2008 by emergency medicine (EM) to the
      specialties of internal medicine, pediatrics, anesthesiology, and family
      medicine. The hypothesis was that EM would receive fewer NIH awards and less
      funding dollars per active physician and per medical school faculty member
      compared to the other four specialties. METHODS: Research Portfolio Online
      Reporting Tools (RePORT) were used to identify NIH-funded grants to 125 of the
      133 U.S. allopathic medical schools for fiscal year 2008 (the most recent year
      with all grant funding information). Eight medical schools were excluded because
      six were not open in 2008, one did not have a website, and one did not have
      funding data available by medical specialty. From RePORT, all grants awarded to
      EM, internal medicine, family medicine, anesthesiology, and pediatric departments
      of each medical school were identified for fiscal year 2008. The authors
      extracted the project number, project title, dollars awarded, and name of the
      principal investigator for each grant. Funds awarded to faculty in divisions of
      EM were accounted for by identifying the department of the EM division and
      searching for all grants awarded to EM faculty within those departments using the
      name of the principal investigator. The total number of active physicians per
      medical specialty was acquired from the Association of American Medical Colleges'
      2008 Physician Specialty report. The total number of faculty per medical
      specialty was collected by two research assistants who independently counted the
      faculty listed on each medical school website. The authors compared the total
      number of NIH awards and total funding per 1,000 active physicians and per 1,000
      faculty members by medical specialty. RESULTS: Of the 125 medical schools
      included in the study, 84 had departments of EM (67%). In 2008, NIH awarded over
      9,000 grants and approximately $4 billion to the five medical specialties of
      interest. Less than 1% of the grants and funds were awarded to EM. EM had the
      second-lowest number of awards and funding per active physician, and the lowest
      number of awards and funding per faculty member. A higher percentage of grants
      awarded to EM were career development awards (26%, vs. a range of 11% to 19% for
      the other specialties) and cooperative agreements (26%, vs. 2% to 10%). In 2008,
      EM was the only specialty of the five not to have a fellowship or T32 training
      grant. EM had the lowest proportion of research project awards (42%, vs. 58% to
      73%). CONCLUSIONS: Compared to internal medicine, pediatrics, anesthesiology, and
      family medicine, EM received the least amount of NIH support per active faculty
      member and ranked next to last for NIH support by active physician. Given the
      many benefits of research both for the specialty and for society, EM needs to
      continue to develop and support an adequate cohort of independent investigators.

PMID- 21854482
TI  - Self-reported financial conflicts of interest during scientific presentations in
      emergency medicine.
AB  - OBJECTIVES: This study was a review of the scientific abstracts presented at a
      national conference for the required conflict of interest (COI) disclosure both
      before the meeting and during presentation. METHODS: All presenters were given
      specific instructions regarding COI reporting at the time of abstract acceptance.
      All poster presentations were required to have a COI statement. Three physicians
      using standardized data abstraction forms reviewed abstracts accepted for poster
      presentation at the 2010 annual meeting of the Society for Academic Emergency
      Medicine (SAEM). Posters were reviewed for the presence of a required COI
      disclosure statement, and these results were compared to the mandatory continuing
      medical education (CME) disclosure form that was sent by the presenters to the
      SAEM central office before the meeting. RESULTS: There were 412 posters accepted
      for presentation at the 2010 SAEM annual meeting. The reviewers observed 382
      (93%) of the total posters for the conference. Sixty-nine abstracts (18%)
      reported a COI. Only 26 (38%) of these were actually reported to the SAEM office
      on the CME disclosure form before the meeting; the remaining 62% were found on
      the poster alone. COI that were reported on the CME disclosure form were found on
      the poster 46% of the time. The remaining posters without a COI actually
      displayed the mandatory disclosure statement only 14% of the time. CONCLUSIONS:
      This review of presentations at a national meeting found a lack of compliance
      with printed guidelines for COI disclosure during scientific presentation.
      Efforts to increase uniformity and clarity may result in increased compliance.

PMID- 21854475
TI  - The long and the short of it: SD1 polymorphism and the evolution of growth trait
      divergence in U.S. weedy rice.
AB  - Growth-related traits, such as greater height, greater biomass, faster growth
      rate and early flowering, are thought to enhance competitiveness of agricultural
      weeds. However, weedy rice, a conspecific weed of cultivated rice (Oryza sativa
      L.), displays variation for growth traits. In the United States, separately
      evolved weedy rice groups have been shown to share genomic identity with exotic
      domesticated cultivars. Through a common garden experiment, we investigated
      whether growth trait divergence has occurred among U.S. weeds and their putative
      cultivated progenitors. We also determined polymorphism patterns in the growth
      candidate gene, SD1, to assess its possible role in the evolution of divergent
      phenotypes. We found considerable growth trait variation among weed groups,
      suggesting that growth trait convergence is not evident among weedy populations.
      Phenotypic divergence of weedy rice from cultivated ancestors is most apparent
      for flowering time. Introgression of a chromosomal block containing the SD1
      allele from tropical japonica, the predominant U.S. rice cultivar, was detected
      in one weedy rice population and is associated with a change in growth patterns
      in this group. This study demonstrates the role of introgressive hybridization in
      evolutionary divergence of an important weed.

PMID- 21854485
TI  - Immediate complications of intravenous contrast for computed tomography imaging
      in the outpatient setting are rare.
AB  - OBJECTIVES: Despite increasing attention to the long-term risks of radiation
      exposure and contrast-induced nephropathy (CIN), institutional guidelines and
      patient consent procedures for contrast-enhanced computed tomography (CECT)
      imaging in the emergency department (ED) setting have focused primarily on more
      immediate complications, directly attributable to the administration of
      intravenous (IV) iodinated contrast administration. Thus, this study sought to
      define the risk of these immediate complications with the overall aim of
      improving institutional guidelines and patient consent procedures. METHODS: This
      was a prospective, consecutive cohort study of patients undergoing CECT of any
      body region in the ED, for complications occurring within 1 week of contrast
      administration, using predefined implicit definitions. Severe complications were
      defined as any of the following requiring medical or surgical intervention:
      bronchospasm with acute respiratory failure, airway obstruction, anaphylactoid
      shock, or acute pulmonary edema. The development of compartment syndrome, lactic
      acidosis, or pulmonary edema within 1 week of contrast administration was also
      considered a severe complication. RESULTS: Of 633 patients, only five (0.8%, 95%
      confidence interval [CI] = 0.3% to 1.8%) reported any immediate complications,
      all of which were classified as minor. No patient developed a reaction meeting
      the study definition of a severe complication. CONCLUSIONS: The frequency of
      severe, immediate complications from CECT imaging that includes IV contrast is
      less than 1%, and the frequency of mild complications is less than 2%. The
      authors conclude that CECT is associated with a very low rate of severe immediate
      complications.

PMID- 21854486
TI  - Evidence-based community consultation for traumatic brain injury.
AB  - OBJECTIVES: The objective was to determine if geospatial techniques can be used
      to inform targeted community consultation (CC) and public disclosure (PD) for a
      clinical trial requiring emergency exception from informed consent (EFIC).
      METHODS: Data from January 2007 to December 2009 were extracted from a Level I
      trauma center's trauma database using the National Trauma Registry of the
      American College of Surgeon (NTRACS). Injury details, demographics, geographic
      codes, and clinical data necessary to match core elements of the clinical trial
      inclusion criteria (Glasgow Coma Scale [GCS] 3-12 and blunt head injury) were
      collected on all patients. Patients' home zip codes were geocoded to compare with
      population density and clustering analysis. RESULTS: Over a 2-year period, 179
      patients presented with moderate to severe traumatic brain injury (TBI). Mapping
      the rate and frequency of TBI patients presenting to the trauma center delineated
      at-risk populations for moderate to severe head injury. Four zip codes had higher
      incidences of TBI than the rest, with one zip code having a very high rate of 80
      per 100,000 population. CONCLUSIONS: Geospatial techniques and hospital data
      records can be used to characterize potential subjects and delineate a high-risk
      population to inform directed CC and public disclosure strategies.

PMID- 21854487
TI  - Factors associated with the use of cervical spine computed tomography imaging in
      pediatric trauma patients.
AB  - OBJECTIVES: The objectives were to identify patient and hospital characteristics
      associated with the use of computed tomography (CT) imaging of the cervical spine
      (c-spine) in the evaluation of injured children and, in particular, to examine
      the influence of hospital setting. METHODS: This was a retrospective cohort of
      children younger than 19 years of age from the Massachusetts Hospital Emergency
      Department (ED) database who were discharged from the ED with an injury diagnosis
      from 2005 through 2009. Multivariable logistic regression was used to analyze
      characteristics associated with CT imaging of the c-spine. RESULTS: Of the
      929,626 pediatric patients diagnosed with an injury in Massachusetts EDs and then
      discharged home, 1.3% underwent CT imaging of the c-spine. Rates of CT imaging
      nearly doubled over the 5 years. In the multivariable model, patient age
      (adjusted odds ratio [AOR] = 2.3, 95% confidence interval [CI] = 2.0 to 2.7 for
      children age 12 to 18 years vs. under 1 year of age) and evaluation outside of a
      pediatric Level I trauma center (AOR = 2.2, 95% CI = 1.1 to 4.3 for children
      evaluated at non Level I trauma centers vs. pediatric Level I trauma centers; AOR
      = 2.1, 95% CI = 0.93 to 4.7 for children evaluated at adult Level I trauma
      centers vs. pediatric Level I trauma centers) were associated with higher rates
      of CT imaging of the c-spine. CONCLUSIONS: Cervical spine CT imaging for children
      discharged from the ED with trauma diagnoses increased from 2005 through 2009.
      Older age and evaluation outside a Level I pediatric trauma center were
      associated with a higher c-spine CT rate. Educational interventions focused
      outside pediatric trauma centers may be an effective approach to decreasing CT
      imaging of the c-spine of pediatric trauma patients.

PMID- 21854488
TI  - VeinViewer-assisted Intravenous catheter placement in a pediatric emergency
      department.
AB  - OBJECTIVES: Peripheral intravenous catheter (PIV) placement is a common, painful,
      and frequently difficult procedure in children. The VeinViewer is a device that
      delineates subcutaneous veins using near-infrared light and video technology. To
      the best of our knowledge, the benefit of this device for PIV placement in
      children in the emergency department (ED) has not been studied. METHODS: The
      authors enrolled a prospective, randomized sample of children aged 0 to 17 years
      who required a nonemergent PIV in a tertiary care pediatric ED. Participants were
      randomized to standard PIV cannulation (SC) or PIV cannulation with the
      VeinViewer (VV). The primary outcome measure was time to PIV placement. Secondary
      outcome measures included number of PIV attempts and pain scores as reported by
      the child, parent or guardian, and nurse using a 100-mm visual analog scale
      (VAS). RESULTS: A total of 323 patients completed the study: 174 boys and 149
      girls. Age, sex, and body mass index (BMI) were not different between groups.
      There were no differences in time to PIV placement, number of PIV attempts, or
      pain scores for the overall study group. However, a planned subgroup analysis of
      children age 0 to 2 years (n = 107) did yield significant results for the
      geometric mean time to place the PIV (121 seconds [VV] vs. 167 seconds [SC], p =
      0.047) and for nurses' perception of pain (median VAS 34 [VV] vs. 46 [SC], p =
      0.01). CONCLUSIONS: While no results were significant for the overall study
      group, subgroup analysis of children age 0 to 2 years suggests that the
      VeinViewer may decrease the time to PIV placement.

PMID- 21854489
TI  - An improved and reliable method for isolation of microvascular endothelial cells
      from human omentum.
AB  - OBJECTIVES: Despite an increasing research demand for human microvascular
      endothelial cells, isolation of primary endothelial cells from human tissue
      remains difficult. The omentum, a highly vascular visceral adipose tissue, could
      provide an excellent source of these cells. METHODS: A reliable method to isolate
      HOMECs has been developed. It consists of initial enzymatic digestion (to deplete
      cell contaminants), followed by further digestion, selective filtration, and
      immunoselection using Dynabeads coated with CD31 antibody. Cultures were
      characterized for expression of endothelial cell markers and their ability to
      undergo VEGF-dependent in vitro tube structure formation. RESULTS: Omental
      derived cultures of microvascular endothelial cells were achieved with <5%
      contamination of other cell types. The endothelial origin of cells was confirmed
      by the constitutive expression of a range of vascular endothelial markers (CD31,
      CD105, vWF) and internalization of DiI-AcLDL. Furthermore, cultures were negative
      for lymphatic endothelial markers, underwent in vitro angiogenesis, and exhibited
      typical endothelial morphology. CONCLUSIONS: This isolation method produces
      homogeneous HOMEC cultures that can be maintained in vitro for at least six
      passages without loss of cellular features characterizing endothelial cells.

PMID- 21854490
TI  - Spinal cord stimulation: predictive parameters of outcome in patients suffering
      from critical lower limb ischemia. A preliminary study.
AB  - INTRODUCTION: The aim of our study is to identify the assessment of metabolic and
      dynamic capillaroscopy parameters that may be predictive of the outcome of spinal
      cord stimulation in patients affected with non-revascularisable chronic critical
      limb ischemia. MATERIALS AND METHODS: Forty patients, 16 female and 24 male,
      average age 69 +/- 8, underwent microcirculatory screening with transcutaneous
      oximetry and dynamic capillaroscopy. Microcirculatory assessment was performed
      before temporary implantation of the spinal cord stimulation stimulator and after
      one month. The following metabolic parameters were considered: TcPO2-TcPCO2 and
      with dependent limb, difference between dependent limb and supine values (Delta
      TcPO2, Delta TcPCO2), change in TcPO2-TcPCO2 after stimulation. Dynamic
      capillaroscopy parameters were recorded. Follow-up visits were scheduled at
      three, six, and twelve months after implantation. The procedure was performed
      placing an Octrode (St. Jude Medical, St. Paul, MN, USA) on the dorsal columns of
      the spinal cord. RESULTS: Two groups were identified on the basis of
      transcutaneous oximetry measurements: group A (22 patients) and group B (18
      patients), responding differently to the postural test. After one month of home
      testing period, there was an improvement in metabolic parameters, differing from
      one group to the other. The morphofunctional data provided by capillaroscopy
      highlighted the percentage of open capillaries poststimulation as being a
      significant parameter, although not mentioned in previous studies. CONCLUSIONS:
      Spinal neuromodulation is an effective therapy option in the management of
      patients affected by non-reconstructable chronic critical limb ischemia.

PMID- 21854491
TI  - Sustained dyskinesias following elective cessation and reactivation of chronic
      subthalamic nucleus deep brain stimulation for a surgical procedure.
AB  - OBJECTIVES: Subthalamic nucleus deep brain stimulation (STN DBS) is effective for
      treatment of levodopa-induced dyskinesias in patients with Parkinson's disease
      (PD). Medical or surgical procedures requiring electrocautery may require
      inactivation of the pulse generators to avoid damage to the lead or extension
      wire or possible reprogramming of the stimulators. This generally causes only
      mild and temporary disability. We report a patient with previously well
      controlled dyskinesias who had severe and prolonged dyskinesias following
      reactivation of deep brain stimulation (DBS) following an orthopedic procedure.
      MATERIALS AND METHODS: Retrospective chart review. RESULTS: The patient underwent
      two orthopedic procedures, each requiring inactivation of DBS. After reactivation
      of DBS, the patient experienced severe dyskinesias that ultimately required
      sedation and ventilation to control large-amplitude dyskinesias. CONCLUSIONS:
      Clinicians caring for PD patients treated with STN DBS should be aware of the
      possible reappearance of severe dyskinesias arising from routine inactivation and
      reactivation of pulse generators for medical or surgical procedures.

PMID- 21854492
TI  - Improved sexual and urinary function in women with sacral nerve stimulation.
AB  - OBJECTIVES:   Urinary and sexual function improve following sacral nerve
      stimulation (SNS) for refractory overactive bladder. No significant associations
      between these changes have been found. Whether improvements in sexual function
      are independent of or secondary to improvements in urinary function remains
      unclear. The aim of this study was to analyze changes in urinary and sexual
      function in a homogeneous sample of patients undergoing SNS for urge urinary
      incontinence and subsequently identify associations between the two. MATERIALS
      AND METHODS:   A prospective database was created. Enrollees underwent a full
      history and physical examination at the first office visit. Multiple-day voiding
      diaries with validated and investigator-designed questionnaires were administered
      at baseline and follow-up as standard implantation procedures and to assess
      changes in urinary and sexual function, respectively. Analyses were completed
      using data from patients who were sexually active at baseline and follow-up.
      RESULTS:   Statistically significant improvements in urinary and sexual function
      occurred according to multiple metrics. Patient global impression scales
      categorized all patients' urinary conditions as improved, with most being less
      severe. Validated urinary symptom and quality of life scores improved
      significantly. After treatment, most patients were incontinent less often with
      sexual activity and felt less restricted from sexual activity by fear of
      incontinence. Validated quantification of sexual function demonstrated
      significant improvements in overall sexual function, arousal, and satisfaction.
      No significant associations between changes in urinary and sexual function were
      noted; however, trends appeared to exist between the two. CONCLUSIONS:   Improved
      sexual function was not significantly associated with improved urinary function
      after SNS despite apparent trends between the two. Larger samples are required to
      definitively demonstrate this conclusion.

PMID- 21854493
TI  - Spinal cord stimulation for visceral pain from chronic pancreatitis.
AB  - BACKGROUND AND OBJECTIVES:   Spinal cord stimulation (SCS) may reduce pain scores
      and improve function in patients with various chronic abdominal pain syndromes
      including chronic pancreatitis. Here described is a large clinical experience in
      SCS for severe chronic pancreatitis. METHODS:   SCS was trialed in 30 patients
      with chronic pancreatitis. SCS trials lasted 7-14 days (median 9 days). SCS lead
      tips were mostly positioned at the T5 (N= 10) or T6 (N= 10) vertebral level.
      RESULTS:   Twenty-four patients (80%) reported at least 50% pain relief on
      completion of the trial. Among these, pre-trial visual analog scale (VAS) pain
      scores averaged 8 +/- 1.6 (standard deviation) and opioid use averaged 165 +/-
      120 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased
      to 3.67 +/- 2 cm (p < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased
      to 105 +/- 101 mg morphine equivalent a day. Six patients failed the trial; one
      was lost to follow-up; in three patients after the implantation, the system had
      to be removed due to infection or lead migration; and 20 were followed for the
      whole year. For 20 patients followed for the whole year, VAS pain scores remained
      low (3.6 +/- 2 cm; p < 0.001) at one year, as did opioid use (48.6 +/- 58 mg
      morphine equivalents). CONCLUSIONS:   SCS may be a useful therapeutic option for
      patients with severe visceral pain from chronic pancreatitis. Prospective trial
      is warranted.

PMID- 21854494
TI  - Triple leads programmed to perform as longitudinal guarded cathodes in spinal
      cord stimulation: a modeling study.
AB  - OBJECTIVE:   In spinal cord stimulation, neurosurgeons increasingly tend to
      implant dual leads. Dual leads (longitudinal bipole/tripole) provide medio
      lateral control over the recruited dorsal column (DC) area by steering the
      injected cathodal currents. However, the DC recruited area is suboptimal when
      dual aligned leads straddling the midline programmed as longitudinal guarded
      cathodes (+-+) are used instead of a single lead placed over the spinal cord
      midline with the same configuration. As a potential improvement, an additional
      third lead between the two aligned leads is modeled to maximize the medio-lateral
      extent of the DCs at the low-thoracic vertebral region (T10-T12). METHODS AND
      MATERIALS:   The University of Twente Spinal Cord Stimulation software (UT-SCS)
      is used in this modeling study. Longitudinal guarded cathodes were modeled on the
      low-thoracic vertebral region (T10-T12) using percutaneous triple lead
      configurations. The central lead was modeled over the spinal cord midline and the
      two lateral leads were modeled at several transverse distances to the midline
      lead. Medio-lateral field steering was performed with the midline lead and the
      second lead on each side to achieve constant anodal current ratios and variable
      anodal current ratios. RESULTS:   Reducing the transverse lead separation
      resulted in increasing the depths and widths of the recruited DC area. The triple
      lead configuration with the least transverse separation had the largest DC
      recruited area and usage range. The maximum DC recruited area (in terms of both
      depth and width) was always found to be larger under variable anodal current
      ratio than constant anodal current ratio conditions. CONCLUSIONS:   Triple leads
      programmed to perform as longitudinal guarded cathodes provide more postoperative
      flexibility than single and dual leads in covering a larger width of the low
      thoracic DCs. The transverse separation between the leads is a major determinant
      of the area and distribution of paresthesia.

PMID- 21854495
TI  - Prospective analysis of the trial period for spinal cord stimulation treatment
      for chronic pain.
AB  - OBJECTIVE: To determine patient preferences regarding the duration of trial
      period. MATERIALS AND METHODS: Forty patients were given a trial of spinal cord
      stimulation. They were questioned daily if they would like to proceed to a
      permanent implant. Three consecutive affirmative answers implied a successful
      trial; three negative replies implied a failed trial. Patients rated daily the
      pain from the surgery, original pain, satisfaction with the stimulator, and the
      duration of the use of the stimulator. RESULTS: The trial duration varied from 3
      to 15 days. Patients with a failed trial took longer to make a decision and also
      experienced prolonged surgical pain. The majority of patients with a successful
      trial experienced more than 50% pain reduction. The rate of infection was 7.5%,
      which has reduced to 2.8% after changing the dressing protocol. CONCLUSIONS: In
      this study, all patients could make a decision in 15 days, with successful trials
      requiring a shorter duration. The conversion rate was similar to rates in
      literature despite patients making a decision without physician input.

PMID- 21854496
TI  - Pathophysiology of the spreading of complex regional pain syndrome revisited: a
      case report.
AB  - OBJECTIVE:   To determine if there is a relationship in our patient developing
      complex regional pain syndrome from a jellyfish and its subsequent spread to the
      contralateral side. METHODS:   Data bases were searched using PubMed and Ovid.
      Keywords searched include "complex regional pain syndrome,""jelly fish," and
      "pathophysiology." RESULTS:   This patient was successfully treated with a spinal
      cord stimulator implantation with bilateral lead placement at thoracic spine (T9)
      stimulating her lower extremities in addition to the leads that had already been
      placed in her cervical spine for her upper extremities. CONCLUSION:   Definite
      knowledge of the pathophysiology of complex regional pain syndrome would allow
      better identification of risk factors for the development of this condition after
      trauma. This patient is at higher risk of developing complex regional pain
      syndrome and should avoid surgeries (such as knee and wrist surgeries) and high
      risk physical activities.

PMID- 21854497
TI  - Peripheral neurostimulation for the treatment of refractory cluster headache,
      long-term follow-up: case report.
AB  - INTRODUCTION:   Cluster headache is a headache syndrome characterized by periodic
      episodes of intense headache with spontaneous remission. There are recent reports
      utilizing occipital nerve stimulation for the successful management of medically
      refractory cases of cluster headache. METHODS:   The case of an 18-year-old boy
      with chronic, refractory, recurrent cluster headaches is presented. He was
      treated surgically with combined occipital, supraorbital, and infraorbital nerve
      stimulation. RESULTS:   Prior to operation, the patient suffered three to four
      episodes of cluster headache per day, for four years. After implantation of
      occipital, supraorbital, and infraorbital nerve stimulators, the patient averages
      at most three to four headaches per month, at 36-month follow-up. CONCLUSION:  
      Peripheral neurostimulation is safe and efficacious in the management of chronic,
      medically refractory cluster headache syndrome. The efficacy of treatment was
      found to be persistent after three years.

PMID- 21854498
TI  - Peripheral nerve field stimulation in the treatment of postlaminectomy syndrome
      after multilevel spinal surgeries.
AB  - INTRODUCTION: Chronic low back pain in patients with postlaminectomy syndrome
      (PLS) is challenging to treat, especially for patients who have undergone
      multilevel surgical procedures. Despite conservative therapy and available
      interventional pain procedures including spinal cord stimulation (SCS) and
      intrathecal therapies, patients may continue with intractable low back pain.
      Peripheral nerve field stimulation (PNFS) may represent an effective alternative
      treatment option for these patients when conventional treatments do not provide
      adequate relief of intractable low back pain. METHODS: Eighteen patients
      underwent an uneventful PNFS trial with percutaneous placement of four temporary
      quadripolar leads (Medtronic, Inc., Minneapolis, MN, USA) placed subcutaneously
      over the lumbar or thoraco-lumbar area. RESULTS: After experiencing excellent
      pain relief over the next two days, temporary leads were removed. The patients
      were implanted with permanent leads and rechargeable or non-rechargeable
      generator two to four weeks after temporary lead removal. All patients reported
      sustained pain relief 12 months after implantation. DISCUSSION: PNFS with use of
      four vertically orientated leads provides an effective treatment option for
      patients with PLS after multilevel surgical procedures with intractable low back
      pain who have failed conservative treatment. PNFS may provide pain relief with
      advantages over conservative treatments and interventional treatments including
      SCS and intrathecal therapy. CONCLUSION: PNFS may be more effective in treating
      intractable low back pain than SCS in patients with PLS after multilevel spinal
      surgeries.

PMID- 21854499
TI  - Subcutaneous peripheral nerve stimulation with inter-lead stimulation for axial
      neck and low back pain: case series and review of the literature.
AB  - OBJECTIVES: While pain in the extremities often responds to treatment using
      spinal cord stimulation (SCS), axial pain is notoriously refractory to SCS.
      Interest in subcutaneous peripheral nerve stimulation (SQ PNS) as an alternative
      to SCS has emerged, but the most appropriate electrode locations and
      neurostimulator programming techniques are not yet clear. METHODS: A
      retrospective review was conducted of consecutive patients evaluated from August
      2009 to December 2010 who had undergone trial of SQ PNS with inter-lead
      stimulation for axial spine pain. Patients proceeding to implant were followed
      postoperatively with routine clinical visits and a survey form at last follow-up.
      Ultrasound was used intraoperatively to ensure placement of electrodes at the
      appropriate depth in patients with larger body mass index. Primary outcome was
      patient-reported pain relief at last follow-up. Literature review was conducted
      by searching MEDLINE (1948-present) and through an unstructured review by the
      authors. RESULTS: Ten patients underwent trial of SQ PNS and six proceeded to
      permanent implantation. Fifty percent (3/6) of implanted patients preferred
      neurostimulation programming that included inter-lead stimulation ("cross-talk").
      Average duration of postoperative follow-up was 4.5 months (range 2-9 months).
      Average patient-reported pain relief at last follow-up was 45% (range 20-80%).
      One patient required re-operation for migration. Patients not proceeding to
      implant had paresthesia coverage but no analgesia. CONCLUSION: SQ PNS is a
      promising therapy for axial neck and back pain based on a small cohort of
      patients. Ultrasound was useful to assist with electrode placement at the most
      appropriate depth beneath the skin. While inter-lead stimulation has been
      preferred by patients in published reports, we did not find it clearly influenced
      pain relief. Future investigations should include a randomized, controlled study
      design, as well as defined implantation technique and neurostimulator programming
      algorithms.

PMID- 21854500
TI  - The use of Raman spectroscopy in the epidemiology of methicillin-resistant
      Staphylococcus aureus of human- and animal-related clonal lineages.
AB  - In order to perform a cost-effective search and destroy policy for methicillin
      resistant Staphylococcus aureus (MRSA), a quick and reliable typing method is
      essential. In an area with a high level of animal-related MRSA ST398, pulsed
      field gel electrophoresis (PFGE) typing and spa-typing are not sufficient to
      discriminate between co-incidental findings and true transmission of MRSA. This
      study is the first to retrospectively show the performance of Raman spectroscopy
      in 16 well-documented outbreaks. We analysed 525 isolates, 286 MRSA ST398 and 239
      from other PFGE clusters with Raman spectroscopy. When epidemiologically linked
      isolates from the outbreaks were analysed with PFGE as the reference standard,
      Raman spectroscopy correctly identified 97% of cases that were indistinguishable
      from the index case. With Raman cluster analysis, the most dominant distinction
      was between MRSA ST398 and other MRSA of human clonal lineages. Within MRSA
      ST398, 22 different Raman clusters were identified. Raman typing correctly
      identified an ST398 (spa type t567) outbreak in a hospital setting. No direct
      correlation was observed between Raman clusters and spa types. We conclude that
      Raman spectroscopy is a quick and reliable method of MRSA typing, which can be
      used in outbreak settings and it is comparable to PFGE, with the added advantage
      that PFGE non-typeable isolates can also be readily typed using the same sample
      preparation protocol.

PMID- 21854501
TI  - New onset diabetes after kidney transplantation in autosomal dominant polycystic
      kidney disease: a retrospective cohort study.
AB  - BACKGROUND: New onset diabetes after transplantation (NODAT) is a common adverse
      outcome of organ transplantation that increases the risk of cardiovascular
      disease, infection and graft rejection. In kidney transplantation, apart from
      traditional risk factors, autosomal dominant polycystic kidney disease (ADPKD)
      has also been reported by several authors as a predisposing factor to the
      development of NODAT, but any rationale for an association between ADPKD and
      NODAT is unclear. We examined the cumulative incidence of NODAT in or own
      transplant population comparing ADPKD patients with non-ADPKD controls. METHODS:
      A retrospective cohort study to determine the cumulative incidence of patients
      developing NODAT (defined by World Health Organization-based criteria and/or use
      of hypoglycaemic medication) was conducted in 79 patients with ADPKD (79
      transplants) and 423 non-ADPKD controls (426 transplants) selected from 613
      sequential transplant recipients over 8 years. Patients with pre-existing
      diabetes as a primary disease or comorbidity and/or with minimal follow up or
      early graft loss/death were excluded. RESULTS: Of the 502 patients (505
      transplants) studied, 86 (17.0%) developed NODAT. There was no significant
      difference in the cumulative incidence of NODAT in the ADPKD (16.5%; CI 13.6
      20.7%) compared with the non-ADPKD (17.1%; CI 8.3-24.6%) control group. Of the 13
      patients in the ADPKD group with NODAT, three required treatment with insulin
      with or without oral hypoglycaemic agents. Among the 73 NODAT patients in the non
      ADPKD group, eight received insulin with or without oral hypoglycaemics.
      Furthermore, of the patients that did develop NODAT, there was no difference in
      the time to its development in patients with and without ADPKD. CONCLUSION: There
      was no evidence of an increased incidence of NODAT in ADPKD kidney transplant
      recipients.

PMID- 21854502
TI  - Effect of exercise on albuminuria in people with diabetes.
AB  - AIM: Spot urine measurement of albumin is now the most commonly accepted approach
      to screening for proteinuria. Exertion prior to the collection may potentially
      influence the result of spot urine albumin estimation. We aim to evaluate the
      effect of exercise on albuminuria in subjects at various stages of diabetic
      nephropathy in comparison with healthy control volunteers. METHODS: Thirty-five
      people with diabetes (19 with normoalbuminuria (NA), nine with microalbuminuria
      (MA) and seven with overt proteinuria (OP)) and nine control subjects were
      assessed. A 1 km treadmill walk was performed. Four spot urine specimens were
      collected: first morning void, immediately prior to exercise, and 1 h and 2 h
      after exercise. A random effects linear regression mixed model was used to assess
      the effect of exercise on albumin/creatinine ratio (uACR). Results are presented
      separately for male and female subjects with diabetes due to a significant
      exercise/gender interaction (P < 0.05). RESULTS: No significant effect of
      exercise on uACR was seen in control subjects. In NA males with diabetes no
      effect of exercise was seen, while in females uACR 1 h after exercise was
      significantly higher than the early morning sample (3.55 mg/mmol (96% confidence
      interval 0.27-6.83). Both female and male diabetes subjects with MA have increase
      in uACR 1 h after exercise (87.8, -24.3-199.4 and 6.7, 2.1-11.3). For both males
      and females with OP, uACR was significantly increased 1 h post exercise (67.5, 22
      113 and 21.6, 8.4-34.8, respectively). In all groups uACR at 2 h after exercise
      was not significantly different to the early morning sample. CONCLUSIONS:
      Exercise increased uACR estimation in normoalbuminuric subjects with diabetes
      with a larger effect in females. Whether exercise unmasks early diabetic
      nephropathy in NA subjects requires further study.

PMID- 21854503
TI  - Efficacy and safety of SBR759, a novel calcium-free, iron(III)-based phosphate
      binder, in Asian patients undergoing hemodialysis: A 12-week, randomized, open
      label, dose-titration study versus sevelamer hydrochloride.
AB  - AIM: SBR759 is a calcium-free, polymeric, iron(III)-based oral phosphate binder,
      in development for the treatment of hyperphosphatemia. The efficacy and safety of
      SBR759 was compared with sevelamer hydrochloride in chronic kidney dialysis
      patients on hemodialysis. METHODS: Japanese and Taiwanese hyperphosphatemic
      patients who were on hemodialysis (n = 203) received starting doses of 3.0 or 4.5
      g/day SBR759 or 2.4 or 4.8 g/day sevelamer-hydrochloride (HCl) based on baseline
      phosphate levels. Daily doses were up-titrated every 2 weeks to reach the Kidney
      Disease Outcomes Quality Initiative (K/DOQI) recommended target serum phosphate
      concentration <=1.7 mmol/L. The key endpoints were proportion of patients
      achieving target serum phosphate and the safety at week 12. RESULTS: SBR759
      showed a superior phosphate response at week 12 compared with sevelamer-HCl (83%
      vs 54% patients; P < 0.0001). Mean serum calcium concentrations were unaffected
      by either treatment. Similar incidences of adverse events and serious adverse
      events were seen with SBR759 and sevelamer-HCl (90.3% vs 94.1% and 5.2% vs 4.4%,
      respectively), but overall discontinuation rates were lower with SBR759 (11.9% vs
      20.6%). The proportion of patients experiencing gastrointestinal disorders was
      lower in SBR759 versus sevelamer-HCl. No treatment-related serious adverse events
      were reported. CONCLUSIONS: SBR759 showed superior phosphate control with a
      favorable tolerability profile compared to sevelamer-HCl in hemodialysis
      patients.

PMID- 21854504
TI  - Circulating anti-glomerular basement membrane autoantibodies against
      alpha3(IV)NC1 undetectable by commercially available enzyme-linked immunosorbent
      assays.
AB  - AIM: Cases with anti-glomerular basement membrane (GBM) disease have been
      reported with linear deposit of immunoglobulin G (IgG) along GBM, but have
      undetectable anti-GBM antibodies in circulation by enzyme linked immunosorbent
      assays (ELISA). We speculated that the structure of the antigens recognized by
      these antibodies may contribute to the negative results of ELISA. METHODS: Sera
      from four patients were collected, with typical linear deposit of IgG along GBM
      but no anti-GBM reactivity by commercial ELISA kits. Circulating anti-GBM
      antibodies were detected by indirect immunofluorescence. Antigen specificity and
      its conformational structure was investigated by western-blot analysis, using
      recombinant human alpha1-alpha5(IV)NC1 and chimeric proteins E(A) and E(B) as
      antigens. RESULTS: The presence of circulating anti-GBM antibodies were confirmed
      by indirect immunofluorescence with linear deposit of IgG towards cryptic
      epitopes along GBM on normal kidney sections. These antibodies did not recognize
      recombinant human alpha1, alpha2, alpha4 or alpha5(IV)NC1, but could blot
      alpha3(IV)NC1 under non-reducing non-boiling conditions on western-blot analysis,
      when the conformational epitope(s) on alpha3(IV)NC1 were thought to be preserved.
      When alpha3(IV)NC1 was prepared under reducing conditions with beta
      mercaptoethanol and/or boiled to destroy the disulfide bonds, the binding with
      the antibodies disappeared. Moreover, these antibodies recognized neither E(A)
      nor E(B) , indicating their distinct epitope repertoire. CONCLUSION: Circulating
      anti-GBM antibodies undetectable by ELISA could recognize cryptic and
      conformation-dependent epitopes restricted on alpha3(IV)NC1, distinct from E(A)
      and E(B) . Indirect immunofluorescence was necessary for antibody detection and
      treatment monitoring under such circumstances.

PMID- 21854505
TI  - Increases in renal replacement therapy in Australia and New Zealand:
      understanding trends in diabetic nephropathy.
AB  - AIM: The incidence of end-stage kidney disease (ESKD) has been increasing
      worldwide, with increasing numbers of older people, people with diabetic
      nephropathy and indigenous people. We investigated the incidence of renal
      replacement therapy (RRT) in Australia and New Zealand (NZ) to better understand
      the causes of these effects. METHODS: Data from the Australia and New Zealand
      Dialysis and Transplant Registry (ANZDATA)registry and relevant population data
      were used to investigate the incidence of RRT in five demographic groups:
      Indigenous and non-indigenous Australians, Maori, Pacific Islanders and other New
      Zealanders, as well as differences between genders and age groups. RESULTS: The
      numbers of patients commencing RRT each year increased by 321% between 1990 and
      2009. This increase was largely driven by increases in patients with diabetic
      nephropathy. In 2009 35% of new patients had ESKD resulting from diabetic
      nephropathy 92% of which were type 2. Indigenous Australians, and Maori and
      Pacific people of NZ have elevated risks of commencing RRT due to diabetic
      nephropathy, although the risks compared with non-indigenous Australians have
      decreased over time. A small element of lead time bias also contributed to this
      increase. Males are more likely to commence RRT due to diabetes than females,
      except among Australian Aborigines, where females are more at risk. There is a
      marked increase in older, more comorbid patients. CONCLUSIONS: Patterns of
      incident renal replacement therapy strongly reflect the prevalence of diabetes
      within these groups. In addition, other factors such as reduced risk of dying
      before reaching ESKD, and increased acceptance of older and sicker patients are
      also contributing to increases in incidence of RRT.

PMID- 21854506
TI  - Uric acid and incident chronic kidney disease in a large health check-up
      population in Taiwan.
AB  - AIM: Uric acid (UA) is strongly associated with the confirmed chronic kidney
      disease (CKD) risk factors, such as hypertension, diabetes and metabolic syndrome
      (MS); however, whether higher UA is independently associated with CKD is still
      debatable. Other studies found that low UA level may reflect inadequate
      protection against oxidant-mediated stress; it is also unknown whether
      hypouricemia may have a harmful effect on the kidney. No studies have examined
      whether there is a J-shaped relationship between UA and incident CKD. METHODS:
      The association between UA and incident kidney disease (Glomerular filtration
      rate <60 mL/min per 1.73 m(2) ) was examined among 94 422 Taiwanese participants,
      aged >=20 years with a mean 3.5 years follow-up in a retrospective cohort. The
      association between UA and CKD was evaluated using Cox models with adjustment for
      confounders. RESULTS: The adjusted hazard ratio (HR) for incident CKD was 1.03
      (95% confidence interval (CI), 1.01 to 1.06) for baseline UA level (increase by 1
      mg/dL). Compared with serum UA in the first quintile (2.0 to 4.5 mg/dL), the
      multivariate-adjusted HR for CKD of the fifth (>=7.3 mg/dL), fourth (6.3 to 7.2
      mg/dL), third (5.5 to 6.2 mg/dL), second (4.6 to 5.4 mg/dL) and hyopuricemia
      (<2.0 mg/dL) were 1.15 (95%CI, 1.01-1.30), 0.98 (95%CI, 0.87-1.10), 1.06 (95%CI,
      0.94-1.19), 1.02 (95%CI, 0.91-1.14) and 1.65(95%CI, 0.53-5.15), respectively. The
      tests for the non-linear association were all not significant for both male and
      female. Gender-specific model revealed only the UA above 7.3 mg/dL with the
      increased risk of new-onset CKD in males. CONCLUSION: Hyperuricemia is a risk
      factor for CKD in Taiwan, future studies are still necessary to determine whether
      hypouricemia increases the risk of CKD.

PMID- 21854507
TI  - Identification of two novel mutations in the OCRL1 gene in two Chinese families
      with Lowe syndrome.
AB  - AIM: Lowe syndrome is a rare, multisystem, X-linked disorder characterized by
      anomalies affecting the eyes, the nervous system and the kidneys. The objective
      of this study was to identify and characterize the clinical manifestations of
      mutations of the causative gene in two Chinese families with Lowe syndrome.
      METHODS: Lowe syndrome was diagnosed based on the clinical manifestations and
      laboratory and imaging findings. Altogether, 164 DNA samples, including samples
      from three affected subjects, five family members (from two families) and 156
      healthy donors, were analyzed to identify the mutations in the OCRL1 gene.
      RESULTS: In family 1, proband 1 had a novel nonsense mutation (c.880G>T) in exon
      10 of the OCRL1. This mutation led to a premature termination of the OCRL1
      protein (p.Glu294X). In family 2, a novel insertion mutation (c.2626dupA) in exon
      24 of OCRL1 was found in proband 2 and his affected elder brother. This mutation
      likely results in the degradation of the OCRL1 protein (p.Met876AsnfsX8). Both
      probands' mothers were identified as carriers of the respective mutations. These
      mutations were not found in the unrelated controls. CONCLUSIONS: Our study
      suggests that the novel nonsense mutation (c.880G>T) in exon 10 and the novel
      insertion mutation (c.2626dupA) in exon 24 of the OCRL1 gene cause Lowe syndrome
      in these two Chinese families.

PMID- 21854508
TI  - Urinary angiotensinogen levels in relation to renal involvement of Henoch
      Schonlein purpura in children.
AB  - AIM: To investigate whether urinary angiotensinogen (UAGT) levels are correlated
      with renal involvement of Henoch-Schonlein purpura (HSP) in children, and to
      explore whether UAGT has any relation to the severity of HSP. METHODS: The study
      sample consisted of 107 patients (50 boys and 57 girls, 6.68+/-2.41 years) with
      clinical diagnosis of HSP. A 24 h urine sample was collected before treatment.
      UAGT levels were measured in patients with HSP in the acute and convalescent
      phases by enzyme linked immunosorbent assay. RESULTS: Urinary
      angiotensinogen/urinary concentration of creatinine levels were significantly
      higher in proteinuric HSP in the acute phase and the convalescent phase (32.02+/
      3.95 and 25.31+/-4.11 ug/g) compared with those with HSP without renal
      involvement (17.26+/-2.60 and 15.14+/-3.81 ug/g) and those with hematuric HSP
      (19.70+/-2.21 and 17.28+/-3.62 ug/g) (P<0.0001 and P<0.01, respectively). Using
      matched urine samples from the same patients, UAGT/urinary concentration of
      creatinine (UCr) levels of proteinuric HSP patients were significantly lower in
      the convalescent phase (25.31 +/- 4.11 ug/g, P<0.01) than in the acute phase
      (32.02+/-3.95 ug/g). UAGT/UCr levels showed positive correlation with 24 h urine
      protein or serum creatinine in both hematuric HSP and proteinuric HSP groups
      during the acute phase (P<0.05). CONCLUSIONS: Urinary angiotensinogen levels were
      remarkably high in the acute phase in the patients with proteinuric HSP,
      suggesting increased UAGT may indicate a series of functional changes in the
      kidney and it may be used as a potential biomarker of severity of HSP to monitor
      the progression of HSP with renal involvement.

PMID- 21854509
TI  - Association between insulin-like growth factor-1 polymorphisms and stomach cancer
      risk in a Japanese population.
AB  - The insulin-like growth factor (IGF) signaling system plays a central role in
      cellular growth, differentiation and proliferation. Although the association
      between IGF1 gene polymorphisms and cancer risk has been evaluated for several
      carcinomas, this association has not yet been examined for stomach cancer. We
      investigated the association between IGF1 polymorphisms and the risk of stomach
      cancer in a Japanese population. A total of 703 patients with stomach cancer and
      1462 non-cancer control subjects were enrolled in this case-control study.
      Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer
      were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in
      multiple logistic regression models. We observed that the C allele in rs1520220
      and the G allele in rs4764887 were significantly associated with stomach cancer
      risk in the per-allele model after adjusting for other risk factors (OR: 1.14
      [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also
      observed a positive and dose-dependent association between the number of risk
      alleles and stomach cancer risk (P-trend: 0.019) when examining the two loci in
      the same model. These associations were still seen after adjusting for potential
      confounders, including sex, age, smoking status, history of diabetes and family
      history of stomach cancer. We did not find any significant interaction between
      these factors and the number of risk alleles. In conclusion, we observed a
      significant association between IGF1 polymorphisms and stomach cancer risk among
      a Japanese population. Examination of the biological significance of IGF1 is
      warranted.

PMID- 21854510
TI  - Liver transplantation in the haemophilia patient.
AB  - Summary.  Hepatitis C is a chronic condition that many persons with haemophilia
      contracted in the 1980s due to the infusion of factor concentrates that did not
      have viral inactivation processes in place. Many patients with haemophilia are
      now living longer lives, well into their eighties due to the improvement of their
      care. The effects of the hepatitis C virus on the liver over time are now being
      realized as this population ages. Although the new treatments for hepatitis C
      have a prolonged response, as demonstrated by a persistent negative viral load,
      many haemophilia patients have either not responded to the therapy or had
      significant side effects to treatment, which prevented continued therapy. Of
      these infected haemophiliacs with liver disease, many have demonstrated a slow
      progressive decline resulting in liver failure, cirrhosis or liver cancer. Liver
      transplant then becomes their only option. This article will review liver
      transplantation in the haemophilia patient highlighting three case studies
      demonstrating the effectiveness of specific short-term factor infusions and other
      haemostatic support to minimize bleeding during the surgical period. These cases
      confirm the opportunity for successful liver transplantation for haemophilia
      patients utilizing specific factor recommendations with minimal bleeding risk.

PMID- 21854511
TI  - Efficacy of prophylaxis and genotype-phenotype correlation in patients with
      severe Factor X deficiency in Iran.
AB  - We aimed to evaluate the effect of regular prophylaxis with a Factor X (FX)
      concentrate for patients with severe FXD in Iran and to assess the correlation of
      the genotype and phenotype in these patients. Ten patients with severe FXD (FX
      activity <1%) were enrolled and characterized during 2010-2011. Prophylaxis with
      20 IU FX P Behring per kg body weight was administered once a week. FX levels,
      were monitored at baseline, 15 and 30 min, 1, 3, 6, 12, 24, 48, 72 and 96 h after
      starting prophylaxis. All patients were followed for 1 year. The mean age of the
      patients was 15 +/- 7.8 years (age range of: 6-27 years). One patient had
      anaphylactic reaction after the first infusion, and the treatment was stopped.
      During one-year follow-up after starting prophylaxis, no bleeding symptoms
      occurred in any patient who tolerated and remained on the prophylaxis programme
      and all of them had a FX level of 1% or above. The maximum level of FX activity
      has been observed at 15 min after starting prophylaxis. A level of 1.5-3.5% was
      detected after 96 h. Homozygous mutations p.Arg40Thr (Arg-1Thr), p.Gly51Arg and
      p.Glu69Lys were detected in patients with intracranial haemorrhage. In our
      patients, significant decrease in symptoms without any complication after
      administration of FX, was demonstrated in all except one patient who had an
      anaphylactic reaction. It seems that the dose of 20 IU kg(-1) could be probably
      the best choice for patients with severe FXD, who require regular prophylaxis.

PMID- 21854512
TI  - New exoelectrogen Citrobacter sp. SX-1 isolated from a microbial fuel cell.
AB  - AIMS: Isolation, identification and characterization of a new exoelectrogenic
      bacterium from a microbial fuel cell (MFC). METHODS AND RESULTS: Exoelectrogenic
      bacterial strain SX-1 was isolated from a mediator-less MFC by conventional
      plating techniques with ferric citrate as electron acceptor under anaerobic
      condition. Phylogenetic analysis of the 16S rDNA sequence revealed that it was
      related to the members of Citrobacter genus with Citrobacter sp. sdy-48 being the
      most closely related species. The bacterial strain SX-1 produced electricity from
      citrate, acetate, glucose, sucrose, glycerol and lactose in MFCs with the highest
      current density of 205 mA m(-2) generated from citrate. Cyclic voltammetry
      analysis indicated that membrane-associated proteins may play an important role
      in facilitating the electrons transferring from bacteria to electrode.
      CONCLUSIONS: This is the first study that demonstrates that Citrobacter species
      can transfer electrons to extracellular electron acceptors. Citrobacter strain SX
      1 is capable of generating electricity from a wide range of substrates in MFCs.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This finding increases the known diversity
      of power generating exoelectrogens and provided a new strain to explore the
      mechanisms of extracellular electron transfer from bacteria to electrode. The
      wide range of substrate utilization by SX-1 increases the application potential
      of MFCs in renewable energy generation and waste treatment.

PMID- 21854513
TI  - Occurrence of adenovirus and other enteric viruses in limited-contact freshwater
      recreational areas and bathing waters.
AB  - AIMS: The goal of this study was to characterize enteric virus concentrations and
      their infectivity in a variety of limited-contact recreation and bathing waters,
      including Great Lakes beaches, inland lakes, rivers, and an effluent-dominated
      urban waterway. Additionally, we evaluated associations between point sources of
      human faecal pollution and enterovirus and adenovirus presence and
      concentrations. METHODS AND RESULTS: Quantitative polymerase chain reaction
      (qPCR) and two cell culture lines were used to identify and quantify viruses in
      water samples. The presence of human adenoviruses F was strongly associated with
      effluent-dominated waters (odds ratio 6.1, confidence interval 2.3, 15.7), as was
      adenovirus concentration; though, neither enterovirus presence nor concentration
      was associated with an effluent source. Samples with high concentrations of qPCR
      targets all tested positive by cell culture on both cell lines, although qPCR
      target concentrations were not correlated with culture values. CONCLUSIONS:
      Adenovirus was strongly associated with point sources of human faecal pollution
      while enterovirus was not, indicating that adenovirus measured by qPCR is a
      better target than enterovirus for identifying wastewater discharges in
      recreational freshwaters. SIGNIFICANCE AND IMPACT OF THE STUDY: The development
      of monitoring for enteric human viral pathogens at recreational waters should
      include adenovirus testing. Further research is needed to interpret the results
      of qPCR testing in relationship to the presence of infectious viruses using cell
      culture.

PMID- 21854514
TI  - Effect of oxygen and temperature on the dynamic of the dominant bacterial
      populations of pig manure and on the persistence of pig-associated genetic
      markers, assessed in river water microcosms.
AB  - AIMS: The aim is to evaluate the dynamic of Bacteroides-Prevotella and Bacillus
      Streptococcus-Lactobacillus populations originating from pig manure and the
      persistence of pig-associated markers belonging to these groups according to
      temperature and oxygen. METHODS AND RESULTS: River water was inoculated with pig
      manure and incubated under microaerophilic and aerobic conditions, at 4 and 20
      degrees C over 43 days. The diversity of bacterial populations was analysed by
      capillary electrophoresis-single-strand conformation polymorphism. The
      persistence of the pig-associated markers was measured by real-time PCR and
      compared with the survival of Escherichia coli and enterococci. Decay was
      characterized by the estimation of the time needed to produce a 1-log reduction
      (T90). The greatest changes were observed at 20 degrees C under aerobic
      conditions, leading to a reduction in the diversity of the bacterial populations
      and in the concentrations of the Pig-1-Bac, Pig-2-Bac and Lactobacillus
      amylovorus markers with a T90 of 10.5, 8.1 and 17.2 days, respectively.
      CONCLUSIONS: Oxygen and temperature were found to have a combined effect on the
      persistence of the pig-associated markers in river waters. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The persistence profiles of the Pig-1-Bac, Pig-2-Bac and
      Lact. amylovorus markers in addition to their high specificity and sensitivity
      support their use as relevant markers to identify pig faecal contamination in
      river waters.

PMID- 21854515
TI  - Effect of starter unit availability on the spectrum of manumycin-type metabolites
      produced by Streptomyces nodosus ssp. asukaensis.
AB  - AIMS: Production of minor asukamycin congeners and its new derivatives by
      combination of targeted genetic manipulations with specific precursor feeding in
      the producer of asukamycin, Streptomyces nodosus ssp. asukaensis. METHODS AND
      RESULTS: Structural variations of manumycins lie only in the diverse initiation
      of the 'upper' polyketide chain. Inactivation of the gene involved in the
      biosynthesis of cyclohexanecarboxylic acid (CHC) turned off the production of
      asukamycin in the mutant strain and allowed an increased production of other
      manumycins with the branched end of the upper chain. The ratio of produced
      metabolites was further affected by specific precursor feeding. Precursor
      directed biosynthesis of a new asukamycin analogue (asukamycin I, 28%) with
      linear initiation of the upper chain was achieved by feeding norleucine to the
      mutant strain. Another asukamycin analogue with the unbranched upper chain
      (asukamycin H, 14%) was formed by the CHC-deficient strain expressing a
      heterologous gene putatively involved in the formation of the n-butyryl-CoA
      starter unit of manumycin A. CONCLUSIONS: Combination of the described techniques
      proved to be an efficient tool for the biosynthesis of minor or novel manumycins.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Production of two novel asukamycin
      derivatives, asukamycins H and I, was achieved. Variations appeared in the upper
      polyketide chain, the major determinant of enzyme-inhibitory features of
      manumycins, affecting their cancerostatic or anti-inflammatory features.

PMID- 21854516
TI  - Functional genomics of dichloromethane utilization in Methylobacterium extorquens
      DM4.
AB  - Dichloromethane (CH(2)Cl(2) , DCM) is a chlorinated solvent mainly produced by
      industry, and a common pollutant. Some aerobic methylotrophic bacteria are able
      to grow with this chlorinated methane as their sole carbon and energy source,
      using a DCM dehalogenase/glutathione S-transferase encoded by dcmA to transform
      DCM into two molecules of HCl and one molecule of formaldehyde, a toxic
      intermediate of methylotrophic metabolism. In Methylobacterium extorquens DM4 of
      known genome sequence, dcmA lies on a 126 kb dcm genomic island not found so far
      in other DCM-dechlorinating strains. An experimental search for the molecular
      determinants involved in specific cellular responses of strain DM4 growing with
      DCM was performed. Random mutagenesis with a minitransposon containing a
      promoterless reporter gfp gene yielded 25 dcm mutants with a specific DCM
      associated phenotype. Differential proteomic analysis of cultures grown with DCM
      and with methanol defined 38 differentially abundant proteins. The 5.5 kb dcm
      islet directly involved in DCM dehalogenation is the only one of seven gene
      clusters specific to the DCM response to be localized within the dcm genomic
      island. The DCM response was shown to involve mainly the core genome of
      Methylobacterium extorquens, providing new insights on DCM-dependent adjustments
      of C1 metabolism and gene regulation, and suggesting a specific stress response
      of Methylobacterium during growth with DCM. Fatty acid, hopanoid and
      peptidoglycan metabolisms were affected, hinting at the membrane-active effects
      of DCM due to its solvent properties. A chloride-induced efflux transporter
      termed CliABC was also newly identified. Thus, DCM dechlorination driven by the
      dcm islet elicits a complex adaptive response encoded by the core genome common
      to dechlorinating as well as non-dechlorinating Methylobacterium strains.

PMID- 21854517
TI  - Genome content of uncultivated marine Roseobacters in the surface ocean.
AB  - Understanding of the ecological roles and evolutionary histories of marine
      bacterial taxa can be complicated by mismatches in genome content between wild
      populations and their better-studied cultured relatives. We used computed
      patterns of non-synonymous (amino acid-altering) nucleotide diversity in marine
      metagenomic data to provide high-confidence identification of DNA fragments from
      uncultivated members of the Roseobacter clade, an abundant taxon of heterotrophic
      marine bacterioplankton in the world's oceans. Differences in gene stoichiometry
      in the Global Ocean Survey metagenomic data set compared with 39 sequenced
      isolates indicated that natural Roseobacter populations differ systematically in
      several genomic attributes from their cultured representatives, including fewer
      genes for signal transduction and cell surface modifications but more genes for
      Sec-like protein secretion systems, anaplerotic CO(2)  incorporation, and
      phosphorus and sulfate uptake. Several of these trends match well with
      characteristics previously identified as distinguishing r- versus K-selected
      ecological strategies in bacteria, suggesting that the r-strategist model
      assigned to cultured roseobacters may be less applicable to their free-living
      oceanic counterparts. The metagenomic Roseobacter DNA fragments revealed several
      traits with evolutionary histories suggestive of horizontal gene transfer from
      other marine bacterioplankton taxa or viruses, including pyrophosphatases and
      glycosylation proteins.

PMID- 21854518
TI  - Structural, mass and elemental analyses of storage granules in methanogenic
      archaeal cells.
AB  - Storage granules are an important component of metabolism in many organisms
      spanning the bacterial, eukaryal and archaeal domains, but systematic analysis of
      their organization inside cells is lacking. In this study, we identify and
      characterize granule-like inclusion bodies in a methanogenic archaeon,
      Methanospirillum hungatei, an anaerobic microorganism that plays an important
      role in nutrient recycling in the ecosystem. Using cryo electron microscopy, we
      show that granules in mature M. hungatei are amorphous in structure with a
      uniform size. Energy dispersive X-ray spectroscopy analysis establishes that each
      granule is a polyphosphate body (PPB) that consists of high concentrations of
      phosphorous and oxygen, and increased levels of iron and magnesium. By scanning
      transmission electron tomography, we further estimate that the mass density
      within a PPB is a little less than metal titanium at room temperature and is
      about four times higher than that of the surrounding cytoplasm. Finally, three
      dimensional cryo electron tomography reveals that PPBs are positioned off-centre
      in their radial locations relative to the cylindrical axis of the cell, and
      almost uniformly placed near cell ends. This positioning ability points to a
      genetic program that spatially and temporally directs the accumulation of
      polyphosphate into a storage granule, perhaps for energy-consuming activities,
      such as cell maintenance, division or motility.

PMID- 21854519
TI  - The USA Food and Drug Administration (FDA) does urological research a favour?

PMID- 21854521
TI  - An interview with Laurence Klotz, MD, FRCSC. Interview by John Fitzpatrick.

PMID- 21854522
TI  - The 'journey of ultrasonography' in the urological community.

PMID- 21854523
TI  - The developing concept of using elective benign and malignant kidneys for renal
      transplantation.

PMID- 21854524
TI  - Urethral trauma. Part II: Types of injury and their management.

PMID- 21854525
TI  - Do mixed histological features affect survival benefit from neoadjuvant platinum
      based combination chemotherapy in patients with locally advanced bladder cancer?

PMID- 21854526
TI  - Do mixed histological features affect survival benefit from neoadjuvant platinum
      based combination chemotherapy in patients with locally advanced bladder cancer?

PMID- 21854527
TI  - First 500 cases of robotic-assisted laparoscopic radical prostatectomy from a
      single uk centre: learning curves of two surgeons.

PMID- 21854528
TI  - First 500 cases of robotic-assisted laparoscopic radical prostatectomy from a
      single uk centre: learning curves of two surgeons.

PMID- 21854529
TI  - Zero-ischaemia robotic and laparoscopic partial nephrectomy (PN).

PMID- 21854530
TI  - What is the current status of revalidation in urology?
AB  - The aim of revalidation (or maintenance of certification) is to reassure
      patients, the general public, employers and other healthcare professionals that
      an individual is fit to practice. It may lead to a reduction in near misses or
      adverse events. The process of revalidation entails a commitment to the provision
      of lifelong learning and assessment of clinical practice that ultimately ensure
      patient safety. Lifelong learning addresses knowledge and skills, whereas
      assessment of clinical practice ensures quality of care. Various learning and
      assessment tools are available in clinical practice; however, the tools for
      revalidation are not validated at specialist level. Further research is needed to
      develop and implement evidence-based structured programmes of revalidation that
      consider the holistic needs of modern urologists.

PMID- 21854531
TI  - Selective bladder-sparing protocol consisting of induction low-dose
      chemoradiotherapy plus partial cystectomy with pelvic lymph node dissection
      against muscle-invasive bladder cancer: oncological outcomes of the initial 46
      patients.
AB  - OBJECTIVE: To evaluate oncological outcomes of muscle-invasive bladder cancer
      (MIBC) patients who were treated with a selective bladder-sparing protocol
      consisting of induction low-dose chemoradiotherapy (LCRT) plus partial cystectomy
      (PC) with pelvic lymph node dissection. PATIENTS AND METHODS: From 1997-2010, 183
      consecutive patients with cT2-4aN0M0 bladder cancer (median age 70 years,
      women/men = 46/137, T2/3/4a = 100/69/14) underwent debulking transurethral
      resection followed by LCRT (radiation at 40 Gy to the small pelvis concurrently
      with two cycles of i.v. cisplatin at 20mg/day for 5 days). Criteria for PC
      include: (i) essentially solitary MIBC or intravesically circumscribed tumours
      (~25% or less of the bladder in area, excluding the bladder neck and trigone);
      (ii) no involvement of bladder neck or trigone; and (iii) clinically, no residual
      disease or minimal amounts of non-invasive disease in the original MIBC site
      after LCRT; otherwise, radical cystectomy (RC) is recommended. Primary and
      secondary endpoints were cancer-specific survival (CSS) and intravesical MIBC
      recurrence-free survival (MRFS) for bladder-preserved patients, respectively.
      RESULTS: Of the 183 patients, 87 (48%) achieved a clinical complete response
      after LCRT and 65 (36%) met the PC criteria; 46 (25%) patients actually underwent
      PC, 86 (47%) had RC, and the remaining 51 (28%) had neither PC, nor RC.
      Histological examination of the 46 PC specimens showed residual muscle-invasive
      disease in three (7%). Overall, 5-year overall survival and CSS rates were 64%
      and 71%, respectively (median follow-up for survivors of 45 months). In the 46 PC
      patients, neither MIBC, nor pelvic recurrence was observed; 5-year CSS and MRFS
      rates were both 100%. In 13 non-PC patients who achieved a complete response
      after LCRT and who met PC criteria but declined PC, 5-year CSS and MRFS rates
      were 74% and 81%, respectively; CSS and MRFS were significantly better in the PC
      group than in the non-PC group (P= 0.025 and 0.002, respectively). CONCLUSIONS:
      In the current selective bladder-sparing protocol, one-third of MIBC patients met
      the PC criteria; when patients from this group underwent PC with pelvic lymph
      node dissection, their oncological outcomes were excellent. Consolidative PC
      potentially reduces MIBC recurrence in the preserved bladder, eventually
      improving survival in properly selected MIBC patients.

PMID- 21854532
TI  - Significant impact of age at diagnosis on the prognosis of Japanese patients with
      pT1 renal cell carcinoma following surgical resection.
AB  - OBJECTIVE: * To retrospectively review oncological outcomes following surgical
      resection in Japanese patients with pT1 renal cell carcinoma (RCC). PATIENTS AND
      METHODS: * The present study included a total of 832 consecutive Japanese
      patients who underwent either radical or partial nephrectomy and were
      subsequently diagnosed as having localized pT1 RCC. * The significance of several
      clinicopathological factors in their postoperative outcomes was analysed.
      RESULTS: * The median (range) age of the 832 patients was 66 (31-90) years.
      Radical and partial nephrectomies were performed for 710 patients (85.3%) and 122
      patients (14.7%), respectively. Distribution of pathological stage was pT1a in
      582 patients (70.0%) and pT1b in 250 patients (30.0%). * During the observation
      period (median 44 months, range 3-114 months), postoperative disease recurrence
      developed in 38 patients (4.6%) and death occurred in 34 (4.1%). The 5-year
      recurrence-free and overall survival rates were 93.6% and 94.1%, respectively. *
      Of several factors examined, only age at diagnosis was identified as an
      independent predictor of both postoperative disease recurrence and overall
      survival in these patients. Furthermore, there were significant differences in
      the recurrence-free and overall survivals among patient groups stratified by age
      at diagnosis. CONCLUSION: * These findings suggest that age at diagnosis is a
      significant predictor of disease recurrence as well as overall survival in
      patients with pT1 RCC following surgical resection; therefore, intensive follow
      up of older patients is necessary even for those with pT1 RCC.

PMID- 21854533
TI  - Long-term toxicity and quality of life up to 10 years after low-dose rate
      brachytherapy for prostate cancer.
AB  - OBJECTIVE: To report on the long-term toxicity outcome for patients with prostate
      cancer treated by low-dose rate (LDR) brachytherapy (BXT). PATIENTS AND METHODS:
      The study population comprised a cohort of men treated in our centre between
      March 1999 and April 2004 with LDR BXT for prostate cancer who had at least 5
      years of follow-up post-implant. Patients who had died or experienced biochemical
      failure were excluded. We contacted eligible patients and asked them to complete
      a questionnaire to assess current urinary, erectile and bowel function. Urinary
      and erectile function was compared pre- and post-treatment and outcomes were
      assessed by treatment modality. RESULTS: Of the 226 LDR BXT-treated patients with
      >5 years of follow-up, 174 (77.0%) responded to the questionnaire. The mean
      International Prostate Symptom Score (IPSS) increased from 6.70 pre-BXT to 7.91
      at follow-up (P = 0.003). Of the patients with mild symptoms pre-BXT (IPSS, 0-7),
      64.2% retained mild symptoms at follow-up, 31.2% developed moderate symptoms
      (IPSS, 8-9) and 4.6% reported severe symptoms (IPSS, 20-35). A good or acceptable
      quality of life (QoL) secondary to urinary symptoms (IPSS QoL, 0-4) was reported
      by 98.0% of respondents. Of those patients potent (International Index of
      Erectile Function-5 >=11) pre-BXT, 62.9% remained potent at follow-up. There were
      no differences in the proportion of patients who were potent when analyzed by the
      number of years post-implant. At follow-up, 51.7% and 45.4% of patients,
      respectively, had normal or mild bowel symptoms as indicated by the European
      Organisation for the Research and Treatment of Cancer questionnaire (QLQ-C30/PR25
      scores, 4-8). Moderate bowel symptoms (QLQ-C30/PR25 scores, 9-12) were reported
      by 2.9% of respondents; none reported severe symptoms. CONCLUSION: The present
      study shows low morbidity after LDR BXT over the long-term for a large cohort of
      patients.

PMID- 21854534
TI  - Evans blue as a selective dye marker for white-light diagnosis of non-muscle
      invasive bladder cancer: an in vitro study.
AB  - OBJECTIVE: To develop a diagnostic method relying on the preferential
      accumulation of a dye in non-muscle-invasive bladder cancer (NMIBC) that is
      visible in conjunction with white-light cystoscopy (WLC). MATERIALS AND METHODS:
      We investigated in detail the permeation of Evans blue in urothelial cell
      carcinoma (UCC) spheroids prepared from T24, J82 and RT-112 human cell lines and
      spheroids composed of normal human urothelial (NHU) cells. To gain more insight
      into the differential accumulation, all spheroids were investigated
      ultrastructurally using transmission electron microscopy (TEM). RESULTS: We found
      that, after exposure to Evans blue for 2 h, UCC spheroids accumulated
      dramatically more dye than spheroids composed of NHU cells. Using TEM it was
      found that the malignant spheroids contain similar ultrastructural
      characteristics, i.e. a wide intercellular space and a decreased number of
      desmosome-like cell attachments, to those from clinical samples of non-papillary
      carcinoma in situ of the bladder. CONCLUSION: We believe the present findings
      could be important for future developments in clinical diagnostics for early
      bladder cancer detection, staging and grading involving WLC.

PMID- 21854535
TI  - The role of transperineal template prostate biopsies in restaging men with
      prostate cancer managed by active surveillance.
AB  - OBJECTIVE: To evaluate the role of transperineal template prostate biopsies in
      men on active surveillance. PATIENTS AND METHODS: In all, 101 men on active
      surveillance for prostate cancer underwent restaging transperineal template
      prostate biopsies at a single centre. Criteria for active surveillance were <=75
      years, Gleason <=3+3, prostate-specific antigen (PSA) <=15 ng/mL, clinical stage
      T1-2a and <=50% ultrasound-guided transrectal biopsy cores positive for cancer
      with <=10 mm of disease in a single core. The number of men with an increase in
      disease volume or Gleason grade on transperineal template biopsy and the number
      of men who later underwent radical treatment were assessed. The role of PSA and
      PSA kinetics were studied. RESULTS: In all, 34% of men had more significant
      prostate cancer on restaging transperineal template biopsies compared with their
      transrectal biopsies. Of these men, 44% had disease predominantly in the anterior
      part of the gland, an area often under-sampled by transrectal biopsies. In the
      group of men who had their restaging transperineal template biopsies within 6
      months of commencing active surveillance 38% had more significant disease. There
      was no correlation with PSA velocity or PSA doubling time. In total, 33% of men
      stopped active surveillance and had radical treatment. CONCLUSIONS: Around one
      third of men had more significant prostate cancer on transperineal template
      biopsies. This probably reflects under-sampling by initial transrectal biopsies
      rather than disease progression.

PMID- 21854536
TI  - The factor VIII inhibitor assays can be standardized: results of a workshop.
AB  - BACKGROUND: The Bethesda and the Nijmegen assays are commonly used for the
      measurement of inhibitor levels in hemophilia A patients. Despite test
      innovations, the between-laboratory coefficient of variation (CVb) of factor VIII
      inhibitor test data in external quality surveys remains very high (40-60%) with a
      high degree of false-negative and false-positive results resulting in undesired
      effects on treatment. OBJECTIVES: Organization of a workshop in order to address
      the causes of this phenomenon and to suggest ways to improve the assays. METHODS:
      Fifteen laboratories showing a high CVb in regular surveys and using a variety of
      methods participated in the wet workshop, which included four different sessions
      where variables probably contributing to the high CVb (e.g. use of [non-]buffered
      plasma, FVIII-deficient plasma, sample dilution and APTT reagents) were
      investigated. RESULTS: The CVb varied from 30% to 70% in the first session of the
      workshop when the participants used their own test settings and reagents. The use
      of buffered normal pooled plasma and FVIII-deficient plasma as a reference sample
      by all participants did not significantly alter the CVb (35-50%) but decreased
      the number of false positives. However, the use of buffered pooled plasma in
      combination with standardized sample dilution procedures by all participants
      showed a significant improvement (CVb, 10-20%). CONCLUSIONS: These results may
      contribute to improvement of FVIII inhibitor testing. However, improved inter
      laboratory comparison of factor VIII inhibitor assay results can only be reached
      when further local standardization is implemented.

PMID- 21854537
TI  - Concentrate-related inhibitor risk: is a difference always real?

PMID- 21854538
TI  - RNA-based therapeutic approaches for coagulation factor deficiencies.
AB  - Substitutive therapy has significantly ameliorated the quality of life of
      patients with coagulation factor deficiencies. However, there are some
      limitations that support research towards alternative therapeutic approaches.
      Here we focus on the rescue of coagulation factor biosynthesis by targeting the
      RNA processing and translation, which would permit restoration of the altered
      gene expression while maintaining the gene regulation in the physiological
      tissues. The essential prerequisite of the three reported RNA-based correction
      approaches (i-iii), which rely on mutation types and are applicable even to large
      size mRNAs, is the presence in cells of the precursor (pre-mRNA) or mature mRNA
      forms. (i) In the F7 gene, modification of the small nuclear RNA U1 (U1 snRNA),
      the key component of the spliceosomal U1 ribonucleoprotein, re-directs correct
      usage of a mutated exon-intron junction, triggering synthesis of correct mRNA and
      secretion of functional factor (F)VII. (ii) Spliceosome-mediated RNA trans
      splicing (SMaRT) between mutated and engineered pre-mRNAs produces normal FVIII
      mRNA and secretion of functional protein. (iii) Aminoglycoside drugs induce
      ribosome readthrough and suppress premature translation termination caused by
      nonsense mutations in FVII, VIII and IX. The rescued expression levels ranged
      from very low (aminoglycosides) to moderate (U1 snRNA and SMaRT), which could
      result in amelioration of the disease phenotypes. These findings prompt further
      studies aimed at demonstrating the clinical translatability of RNA-based
      strategies, which might open new avenues in the treatment of coagulation factor
      deficiencies.

PMID- 21854539
TI  - Genetic determinants of platelet reactivity during acetylsalicylic acid therapy
      in diabetic patients: evaluation of 27 polymorphisms within candidate genes.
AB  - AIMS: Decreased platelet responsiveness to acetylsalicylic acid (ASA) reported
      previously in diabetic patients could be attributed to patient-based, clinical,
      genetic and cellular factors. The objective of the present study was to
      investigate the effect of the genomic polymorphism on the platelet reactivity in
      diabetic patients treated with ASA. METHODS AND RESULTS: The study cohort
      consisted of 295 Caucasians with diabetes type 2 who had been taking ASA tablets
      at the dose of 75 mg per day for at least 3 months for primary or secondary
      prevention of myocardial infarction (MI). Platelet reactivity analyzes were
      performed using VerifyNow ASA and PFA-100 assays. Genotyping for the selected 27
      single nucleotide polymorphisms (SNPs) within 19 genes was performed using a
      Sequenom iPLEX platform. The results indicate that the statistically significant
      differences in platelet reactivity were observed in the PFA-100 assay for SNPs in
      following genes: TXBA2R (rs1131882), ADRA2A (rs4311994), PLA2G7 (rs7756935) and
      9p21.3 (rs10120688) (P = 0.02, P = 0.03, P = 0.02, P = 0.03, respectively, all
      significance levels corrected for multiple comparisons). When using the VerifyNow
      ASA test, a weak nominal statistical significance (i.e. before multiple
      comparison testing) was observed for two SNPs in the GPVI gene: rs1671152 and
      rs1613662 [P = 0.025 (0.5) for both SNPs, corrected for multiple comparisons
      test]. CONCLUSIONS: The results from the present study suggest that the four
      analyzed genes may contribute to platelet reactivity measured with the PFA-100
      assay in the diabetic population treated with ASA.

PMID- 21854540
TI  - Combined influence of proton-pump inhibitors, calcium-channel blockers and
      CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of
      atherothrombotic events after percutaneous coronary intervention.
AB  - BACKGROUND: The carriage of CYP2C19*2 and the use of proton-pump inhibitors
      (PPIs) and calcium-channel blockers (CCBs) has been associated with the
      diminished efficacy of clopidogrel. However, previous studies have only assessed
      the isolated impact of these risk factors for clopidogrel poor response.
      OBJECTIVES: The aim of the present study was to investigate the impact of the
      combined presence of three risk factors for clopidogrel poor response, that is,
      the use of CCBs, PPIs and the carriage of CYP2C19*2, on on-treatment platelet
      reactivity and the occurrence of atherothrombotic events in 725 patients on dual
      antiplatelet therapy undergoing elective coronary stenting. METHODS: In a
      prospective, follow-up study, on-treatment platelet reactivity was quantified
      using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12
      assay. The clinical study endpoint was the composite of all-cause mortality,
      myocardial infarction, stent thrombosis and stroke at 1 year after stenting.
      RESULTS: Patients with either one or more than one risk factor exhibited
      increased platelet reactivity (mean relative increase one risk factor: 11% and >
      1 risk factor: 22%, respectively). Sixty-four events occurred during follow-up
      (8.8% of the study population). Patients with one risk factor for clopidogrel
      poor response did not have an increased risk of the composite endpoint. However,
      patients using both CCBs and PPIs and carriers of CYP2C19*2 who used CCBs had a
      statistically significant increased risk of the composite endpoint [hazard
      ratio(HR)(adj) 2.2 95% CI, 1.0-5.3, P = 0.044 and HR(adj) 3.3 95% CI, 1.1-9.8, P
      = 0.032, respectively]. CONCLUSIONS: The presence of more than one of the three
      investigated risk factors for clopidogrel poor response is associated with an
      increased risk of adverse cardiovascular events within 1 year after elective
      coronary stenting.

PMID- 21854541
TI  - Oncostatin M decreases interleukin-1 beta secretion by human synovial fibroblasts
      and attenuates an acute inflammatory reaction in vivo.
AB  - Oncostatin M (OSM) is a pleiotropic cytokine of the IL-6 family and displays both
      pro-inflammatory and anti-inflammatory activities. We studied the impact of OSM
      on the gene activation profile of human synovial cells, which play a central role
      in the progression of inflammatory responses in joints. In synovial cells
      stimulated with lipopolysaccharide and recombinant human granulocyte-macrophage
      colony-stimulating factor, recombinant human OSM and native OSM secreted by human
      granulocytes both reduced the gene expression and secretion of IL-1beta and
      CXCL8, but increased that of IL-6 and CCL2. This impact on synovial cell
      activation was not obtained using IL-6 or leukaemia inhibitory factor. Signal
      transducer and activator of transcription-1 appeared to mediate the effects of
      OSM on stimulated human synovial fibroblasts. In the murine dorsal air pouch
      model of inflammation, OSM reduced the expression of the pro-inflammatory
      cytokines IL-1beta and TNF-alpha in lining tissues, and their presence in the
      cavity. These results as a whole suggest an anti-inflammatory role for OSM,
      guiding inflammatory processes towards resolution.

PMID- 21854542
TI  - Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human
      myometrial cells.
AB  - Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects
      of many hormones and drugs. However, recently PGI(2) , acting via cAMP/PKA, was
      found to increase contraction-associated protein expression in myometrial cells
      and to promote oxytocin-driven myometrial contractility. Cyclo-oxygenase-2 (COX
      2) is the rate-limiting enzyme in prostaglandin synthesis, which is critical to
      the onset and progression of human labour. We have investigated the impact of
      cAMP on myometrial COX-2 expression, synthesis and activity. Three cAMP agonists
      (8-bromo-cAMP, forskolin and rolipram) increased COX-2 mRNA expression and
      further studies confirmed that this was associated with COX-2 protein synthesis
      and activity (increased PGE(2)  and PGI(2)  in culture supernatant) in primary
      cultures of human myometrial cells. These effects were neither reproduced by
      specific agonists nor inhibited by specific inhibitors of known cAMP-effectors
      (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and
      another recently described cAMP-effector PDZ-GEF(1-2) , without changing the
      response to cAMP. We found that MAPK activation mediated the cAMP effects on COX
      2 expression and that PGE(2)  acts through EP-2 to activate MAPK and increase COX
      2. These data provide further evidence in support of a dual role for cAMP in the
      regulation of myometrial function.

PMID- 21854544
TI  - Easy fabrication of a new type of mouthguard incorporating a hard insert and
      space and offering improved shock absorption ability.
AB  - The positive effects of wearing a mouthguard have been indicated in various
      epidemiological surveys and experiments, and their usage appears to be increasing
      in many sports. However, many preventable sports-related dental injuries still
      occur even with the use of a conventional mouthguard. We have developed a
      mouthguard (the Hard & Space mouthguard) with sufficient injury prevention
      ability (more than 95% shock absorption ability against impact with a steel ball
      carrying 15.2 kg m(2) S(-2) potential energy) and ease of clinical application.
      This mouthguard consists of an outer and an inner EVA layer and a middle layer of
      acrylic resin (hard insert), with a space to prevent contact between the inner
      surface of the mouthguard and the buccal surfaces of the maxillary front teeth or
      teeth already weakened through prior damage or treatment. The purpose of this
      article is to describe the method by which the Hard & Space mouthguard may easily
      be fabricated. We believe that this new type of mouthguard has the potential to
      reduce sports-related dental injuries.

PMID- 21854543
TI  - Tyrosine kinase gene fusions in cancer: translating mechanisms into targeted
      therapies.
AB  - Tyrosine kinase fusion genes represent an important class of oncogenes associated
      with leukaemia and solid tumours. They are produced by translocations and other
      chromosomal rearrangements of a subset of tyrosine kinase genes, including ABL,
      PDGFRA, PDGFRB, FGFR1, SYK, RET, JAK2 and ALK. Based on recent findings, this
      review discusses the common mechanisms of activation of these fusion genes.
      Enforced oligomerization and inactivation of inhibitory domains are the two key
      processes that switch on the kinase domain. Activated tyrosine kinase fusions
      then signal via an array of transduction cascades, which are largely shared. In
      addition, the fusion partner provides a scaffold for the recruitment of proteins
      that contribute to signalling, protein stability, cellular localization and
      oligomerization. The expression level of the fusion protein is another critical
      parameter. Its transcription is controlled by the partner gene promoter, while
      translation may be regulated by miRNA. Several mechanisms also prevent the
      degradation of the oncoprotein by proteasomes and lysosomes, leading to its
      accumulation in cells. The selective inhibition of the tyrosine kinase activity
      by adenosine-5'-triphosphate competitors, such as imatinib, is a major
      therapeutic success. Imatinib induces remission in leukaemia patients that are
      positive for BCR-ABL or PDGFR fusions. Recently, crizotinib produced promising
      results in a subtype of lung cancers with ALK fusion. However, resistance was
      reported in both cases, partially due to mutations. To tackle this problem,
      additional levels of therapeutic interventions are suggested by the complex
      mechanisms of fusion tyrosine kinase activation. New approaches include
      allosteric inhibition and interfering with oligomerization or chaperones.

PMID- 21854545
TI  - Recovering the function and esthetics of fractured teeth using several
      restorative cosmetic approaches. Three clinical cases.
AB  - The teeth most commonly affected by trauma are the maxillary central incisors.
      The most frequent types of traumatic dental injuries to permanent teeth are
      enamel fractures, enamel and dentine fractures, and enamel and dentine fractures
      with pulp involvement. This article describes three clinical cases with different
      levels of traumatized maxillary incisors and several cosmetic approaches for
      recovery of the esthetics and the masticatory function, as well as the
      social/psychological aspects of treatment. All cases involved young adult men.
      The three clinical cases involve dentin and enamel fractures, dentin and enamel
      fractures with pulp exposure, and dentin and enamel fractures with pulp exposure
      associated with root fracture. The cosmetic treatments used to resolve fractures
      were direct composite resin by layering technique, indirect all-ceramic
      restorations (laminate veneer and ceramic crowns over the teeth), and immediate
      implant after extraction followed by immediate loading (ceramic abutments with
      ceramic crown over implant). In all three cases, excellent functional and
      esthetic results were achieved by use of these treatment modalities. The patients
      were very satisfied with the results.

PMID- 21854546
TI  - Folic acid may be a potential addition to diabetic foot ulcer treatment - a
      hypothesis.
AB  - Delayed wound healing in diabetes is a challenging medical and societal problem
      for which there is currently no efficacious treatment. One of the major
      contributors of this problem is nitric oxide (NO) deficiency. NO is a critical
      signalling molecule essential for normal wound repair. Sustained hyperglycaemia
      in diabetes leads to increased vascular superoxide production, which inactivates
      NO and causes vascular dysfunction. New therapeutic regiments and strategies to
      enhance endothelial NO production are a new hope to improve impaired diabetic
      wound healing. One of the agents that have the ability to improve endothelial NO
      generation in diabetic patients is folic acid. Folic acid ability to conserve NO
      bioactivity may be due to homocysteine-lowering effects of folates, antioxidant
      actions and effects on cofactor availability. Considering these data, we
      hypothesised that folic acid supplementation may ameliorate delayed diabetic
      wound healing by increasing NO bioavailability. The potential of exogenous folic
      acid as an inexpensive and safe oral therapy stimulates ongoing investigations.

PMID- 21854547
TI  - Use of vacuum-assisted closure (VACTM) in high-energy complicated perineal
      injuries: analysis of nine cases.
AB  - Our study reviewed nine patients who were treated with the VACTM Abdominal
      Dressing System after suffering pelvic fractures and soft tissue loss after high
      energy pelvic trauma. Between March 2008 and August 2009, our clinic treated nine
      patients with complicated perineal injuries from high-energy pelvic trauma with
      multiple irrigation and debridement procedures and broad-spectrum antibiotics.
      Protective ostomies were created for all nine patients. Required interventions
      were made for associated injuries, and VACTM application was started. All
      patients were male, with an average age of 24.3 (range 21-32) years, and a mean
      injury severity score of 36.4 (range 16-59). Wound diameters ranged from 15 to 30
      cm, and wound depths ranged from 5 to 25 cm. The injuries included one traumatic
      bilateral hemipelvectomy, and three unilateral and two bilateral lower extremity
      amputations. Intensive care unit length of stay averaged 12 (6-19) days, and
      average hospital length of stay was 44.12 (31-64) days. Beginning at an average
      of day 17 (+/-5.9 days) post-injury, wound cultures detected no bacterial
      colonisation. One patient died on the sixth day after injury from septic
      complications. Two patients' wounds were closed by primary closure, and six
      patients' wounds were closed by split thickness grafts after an average of 31.4
      (17-50) days. Optimal treatment of high-energy perineal injuries requires early
      and extensive debridement and rich irrigation. The application of the VACTM
      system as temporary coverage of large complex wounds in the pelvic region
      enhances wound healing and facilitates an early grafting process.

PMID- 21854548
TI  - Antimicrobial sutures and prevention of surgical site infection: assessment of
      the safety of the antiseptic triclosan.
AB  - This article is based on a second Hygienist Panel meeting held in London on 16-17
      June 2010. The Panel discussed the current use of antimicrobials and care bundles
      in the prevention of surgical site infection; the need to comply with good
      antibiotic stewardship, to reduce the risk of antibiotic-resistant and emergent
      organisms; and the need to revisit the use of antiseptics. The discussion was
      driven by concerns of the use of triclosan, which had been raised by a
      publication from the Scientific Committee on Consumer Products of the Directorate
      General for Health and Consumers, European Commission. Uncertainties that
      excessive use of triclosan for preservation and in cosmetics could select
      naturally resistant environmental organisms or induce reduced triclosan
      susceptibility or antibiotic resistance were considered. It was concluded that
      the uses of triclosan with demonstrable health benefits, as in some medical
      applications (such as antimicrobial sutures), need to be distinguished from those
      where there is no proven benefit, such as its use in certain consumer products.
      The addition of triclosan to a product must be substantiated in any claim of
      preventive or therapeutic health benefit. Triclosan is the most widely studied
      biocide and this same level of information should be available for other
      topically used antimicrobials, which are widely used in surgical practice and
      chronic wound care.

PMID- 21854549
TI  - Leg ulcers associated with Klinefelter's syndrome: a case report and review of
      the literature.
AB  - We present the case of a young man with type II diabetes, stage III chronic
      kidney disease, hypertension, obstructive sleep apnea and diabetes who presented
      to the Georgetown University Hospital Center for Wound Healing with refractory
      lower extremity ulcers. Autoimmune work-up was negative. However, chromosome
      analysis showed a genetic variant of Klinefelter's syndrome (48 XXYY). Lower
      extremity ulceration is a recognised complication of Klinefelter's syndrome. The
      pathogenesis of ulcers in this endocrinopathy is unclear, but associations with
      abnormalities of fibrinolysis and prothrombotic states are reported. This case
      emphasises the importance of considering Klinefelter's syndrome in the
      differential diagnosis of a sterile male patient with non healing lower extremity
      ulcers.

PMID- 21854550
TI  - Voluntary resistance wheel exercise during post-natal growth in rats enhances
      skeletal muscle satellite cell and myonuclear content at adulthood.
AB  - AIM: To determine whether voluntary free wheel (FW) or resistance wheel (RW)
      exercise or reduced muscle activity would influence maturational increases in
      muscle mass and the number of satellite cells (SCs) and myonuclei (MN) accrued by
      adulthood. METHODS: Hind limb muscles of male rats housed with, or without, FWs
      from 4 to 5, 7 or 10 weeks of age, and rats housed with RWs from 4 to 10 week of
      age, were evaluated. To assess the effect of reduced muscle activity,
      gastrocnemius muscles of 4-week-old rats were injected with botulinum toxin (Btx)
      and collected at 7 weeks of age. Muscle fibre size and the frequency of Pax7
      positive SCs and MN were determined in 7- and 10-week-old muscles via
      immunohistochemical methods. RESULTS: Free wheel exercise enhanced muscle growth
      and the frequency of SCs in the medial gastrocnemius (MG) (threefold) and vastus
      lateralis (VL) (twofold) of rats at 10 week of age. Resistance wheel exercise
      increased the number of SCs and MN (22-30%), with more muscle fibre nuclei being
      associated with larger fibre size, in the soleus, MG and VL muscles. Btx impaired
      the normal increases in muscle fibre size and the accrual of MN but not SCs.
      CONCLUSION: A greater volume of exercise during maturational growth was important
      for enhancing SC numbers, whereas their conversion to MN required higher
      intensity exercise. The enhanced muscle fibre nuclear populations may influence
      the capacity of the muscle to adapt to exercise, injury or disuse in later
      adulthood.

PMID- 21854551
TI  - Effects of renal denervation on the NKCC2 cotransporter in the thick ascending
      limb of the loop of Henle in rats with congestive heart failure.
AB  - AIM: Congestive heart failure (CHF) is associated with increased renal
      sympathetic nerve activity and renal sodium retention. Rats with CHF display
      increased expression of the Na-K-2Cl cotransporter (NKCC2) in the renal medullary
      thick ascending limb of the loop of Henle (mTAL), and arginine vasopressin (AVP)
      stimulated cAMP formation in mTAL segments is increased in rats with CHF. The aim
      of the study was to investigate the role of RSNA on cAMP formation and NKCC2
      expression in mTAL in rats with CHF. METHODS: Congestive heart failure was
      induced in male Wistar rats by ligation of the left anterior descending coronary
      artery. Bilateral surgical renal denervation (DNX) was performed 3 weeks later.
      Two weeks after DNX, mTAL segments were isolated and stimulated with AVP.
      RESULTS: Congestive heart failure rats displayed increased mTAL NKCC2 expression
      (2.5 +/- 0.5 vs. 1 +/- 0.2 in Sham rats), which was abolished by DNX. Bilateral
      denervation decreased basal cAMP levels in unstimulated tubules from CHF rats
      (CHF: 12.56 +/- 7.73 fmol MUg(-1) protein vs. DNX-CHF: 7.94 +/- 4.33; P < 0.05),
      as well as from Sham rats (SHAM: 4.70 +/- 1.38 vs. DNX-SHAM: 2.36 +/- 1.52; P <
      0.05). mTAL segments from DNX-CHF and DNX-Sham rats showed decreased AVP (10(-6)
      M)-stimulated cAMP formation, compared with CHF (CHF: 11.92 +/- 4.89 fmol MUg(-1)
      protein vs. DNX-CHF: 4.68 +/- 2.47; P < 0.05) and Sham (SHAM: 10.78 +/- 5.59 vs.
      DNX-SHAM: 4.89 +/- 2.62; P < 0.05). CONCLUSION: These results indicate that the
      renal sympathetic nerves have an effect on NKCC2 expression in the mTAL and might
      have an effect on cAMP formation in the TAL in CHF.

PMID- 21854552
TI  - Post-operative pain following coblation or monopolar electrocautery tonsillectomy
      in children: a prospective, single-blinded, randomised comparison.
AB  - OBJECTIVE: To compare post-operative pain following tonsillectomy by either
      coblation or monopolar electrocautery in children. DESIGN: A parallel-designed,
      prospective, single-blinded, randomised trial. SETTING: Ambulatory surgical
      facility. STUDY PARTICIPANTS: Eighty otherwise healthy paediatric patients
      undergoing coblation or electrocautery tonsillectomy by a fellowship-trained
      paediatric otolaryngologist. MAIN OUTCOME MEASURES: (i) The number of post
      operative days with severe pain based on subjective qualification by the
      caretaker, (ii) post-operative days with pain rated >= 5 on a scale of 1-10,
      (iii) post-operative days requiring oral paracetamol/acetaminophen with codeine
      solution and (iv) post-operative days until resumption of a regular diet were
      assessed and recorded daily using a post-operative pain survey as a form of daily
      diary that was returned at the 2-week follow-up visit. RESULTS: Patients were
      consecutively enrolled into two groups of 40 patients. Average ages were 5.2
      years for coblation tonsillectomy and 6.0 years for electrocautery tonsillectomy.
      The average number of post-operative days with severe pain was 4.2 for coblation
      and 5.9 for electrocautery (P = 0.006), days rating pain >= 5 were 3.6 for
      coblation and 4.8 for electrocautery (P = 0.037), days of codeine use were 2.5
      for coblation and 2.9 for electrocautery (P = 0.324), and days until resumption
      of a regular diet were 5.2 for coblation and 6.2 for electrocautery (0.329).
      CONCLUSIONS: Coblation tonsillectomy may reduce post-operative pain and the time
      until resumption of a regular diet compared to electrocautery tonsillectomy.

PMID- 21854554
TI  - Use of Staurenghi lens angiography in the management of posterior uveitis.
AB  - PURPOSE: Retinal vasculitis is an important component of posterior uveitis. It
      may be difficult to detect either clinically or with conventional angiography. We
      assessed the role of Staurenghi lens angiography (SLA) in the diagnosis and
      management of patients with posterior uveitis. METHODS: A total of 26 patients
      attending the St Paul's Eye Unit uveitis clinic with posterior uveitis underwent
      wide-angle (150 degree) retinal angiography with the Heidelberg Retina Angiograph
      2 Scanning Laser Ophthalmoscope using the Staurenghi SLO 230 contact lens. We
      determined the percentage of patients in whom this imaging modality assisted in
      diagnosing and quantifying the extent of vasculitis, planning treatment or
      monitoring disease activity. RESULTS: Staurenghi lens angiography assisted in
      diagnosing and quantifying the extent of vasculitis in 62% of patients, and in
      planning laser photocoagulation or immunosuppression titration in 62% of patients
      and enhanced disease monitoring in 35% of patients. In 31% of cases, SLA revealed
      vasculitis that was not evident clinically. CONCLUSION: Staurenghi lens
      angiography is a valuable tool in the management of patients with posterior
      uveitis and can be used for the diagnosis, treatment and follow-up of these
      patients.

PMID- 21854553
TI  - Nanoparticles for transcutaneous vaccination.
AB  - The living epidermis and dermis are rich in antigen presenting cells (APCs).
      Their activation can elicit a strong humoral and cellular immune response as well
      as mucosal immunity. Therefore, the skin is a very attractive site for
      vaccination, and an intradermal application of antigen may be much more effective
      than a subcutaneous or intramuscular injection. However, the stratum corneum (SC)
      is a most effective barrier against the invasion of topically applied vaccines.
      Products which have reached the stage of clinical testing, avoid this problem by
      injecting the nano-vaccine intradermally or by employing a barrier disrupting
      method and applying the vaccine to a relatively large skin area. Needle-free
      vaccination is desirable from a number of aspects: ease of application, improved
      patient acceptance and less risk of infection among them. Nanocarriers can be
      designed in a way that they can overcome the SC. Also incorporation into
      nanocarriers protects instable antigen from degradation, improves uptake and
      processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA
      vaccines. In addition, sustained release systems may build a depot in the tissue
      gradually releasing antigen which may avoid booster doses. Therefore,
      nanoformulations of vaccines for transcutaneous immunization are currently a very
      dynamic field of research. Among the huge variety of nanocarrier systems that are
      investigated hopes lie on ultra-flexible liposomes, superfine rigid nanoparticles
      and nanocarriers, which are taken up by hair follicles. The potential and
      pitfalls associated with these three classes of carriers will be discussed.

PMID- 21854555
TI  - A first-generation integrated tammar wallaby map and its use in creating a tammar
      wallaby first-generation virtual genome map.
AB  - BACKGROUND: The limited (2X) coverage of the tammar wallaby (Macropus eugenii)
      genome sequence dataset currently presents a challenge for assembly and anchoring
      onto chromosomes. To provide a framework for this assembly, it would be a great
      advantage to have a dense map of the tammar wallaby genome. However, only limited
      mapping data are available for this non-model species, comprising a physical map
      and a linkage map. RESULTS: We combined all available tammar wallaby mapping data
      to create a tammar wallaby integrated map, using the Location DataBase (LDB)
      strategy. This first-generation integrated map combines all available information
      from the second-generation tammar wallaby linkage map with 148 loci, and
      extensive FISH mapping data for 492 loci, especially for genes likely to be
      located at the ends of wallaby chromosomes or at evolutionary breakpoints
      inferred from comparative information. For loci whose positions are only
      approximately known, their location in the integrated map was refined on the
      basis of comparative information from opossum (Monodelphis domestica) and human.
      Interpolation of segments from the opossum and human assemblies into the
      integrated map enabled the subsequent construction of a tammar wallaby first
      generation virtual genome map, which comprises 14336 markers, including 13783
      genes recruited from opossum and human assemblies. Both maps are freely available
      at http://compldb.angis.org.au. CONCLUSIONS: The first-generation integrated map
      and the first-generation virtual genome map provide a backbone for the chromosome
      assembly of the tammar wallaby genome sequence. For example, 78% of the 10257
      gene-scaffolds in the Ensembl annotation of the tammar wallaby genome sequence
      (including 10522 protein-coding genes) can now be given a chromosome location in
      the tammar wallaby virtual genome map.

PMID- 21854556
TI  - Migraine headaches among university students using ID Migraine test as a
      screening tool.
AB  - BACKGROUND: Migraine is a significant health problem, especially for the young
      people, due to its frequency and accompanying morbidity, causing disability and
      loss of performance. In this study, our aim was to determine the prevalence of
      migraine headaches among university students in Edirne, a Turkish city. METHODS:
      In this cross-sectional and descriptive study, study population was composed of
      students registered to Trakya University in the academic year of 2008-2009. Out
      of these, 3694 of them accepted to participate. Participants who had two or more
      headaches in the last 3 months formed the headache group. Afterwards, two
      preliminary questions were applied to the headache group and participants with at
      least one affirmative response were asked to perform the validated ID-MigraineTM
      test. RESULTS: The mean age of 3694 students participated in the study was 19.23
      +/- 1.84 (17-39 years), with adolescents:adult ratio being 2.5:1. 1613 students
      (43.7%) did have at least two headaches in the last three months. Migraine-type
      headache was detected in 266 subjects (7.2%) based on the ID-MigraineTM test. Of
      the migraine group, 72 were male (27.1%) and 194 were female (72.9%). There was
      no significant difference in migraine prevalence between adolescent and adult age
      groups. CONCLUSIONS: With a prevalence similar to adults, primary care physicians
      should be aware of the probability of migraine headaches in university students
      in order to maintain a successful school performance.

PMID- 21854557
TI  - Breast gangrene.
AB  - BACKGROUND: Breast gangrene is rare in surgical practice. Gangrene of breast can
      be idiopathic or secondary to some causative factor. Antibiotics and debridement
      are used for management. Acute inflammatory infiltrate, severe necrosis of breast
      tissue, necrotizing arteritis, and venous thrombosis is observed on
      histopathology. The aim of was to study patients who had breast gangrene.
      METHODS: A prospective study of 10 patients who had breast gangrene over a period
      of 6 years were analyzed RESULTS: All the patients in the study group were
      female. Total of 10 patients were encountered who had breast gangrene. Six
      patients presented with breast gangrene on the right breast whereas four had on
      left breast. Out of 10 patients, three had breast abscess after teeth bite
      followed by gangrene, one had iatrogenic trauma by needle aspiration of
      erythematous area of breast under septic conditions. Four had history of
      application of belladonna on cutaneous breast abscess and had then gangrene. All
      were lactating female. Amongst the rest two were elderly, one of which was a
      diabetic who had gangrene of breast and had no application of belladonna. All
      except one had debridement under cover of broad spectrum antibiotics. Three
      patients had grafting to cover the raw area. CONCLUSION: Breast gangrene occurs
      rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and
      the iatrogenic trauma by needle aspiration of breast abscess under unsterlised
      conditions could be causative. Uncontrolled diabetes can be one more causative
      factor for the breast gangrene. Belladonna application as a topical agent could
      be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is
      antibiotics and debridement.

PMID- 21854558
TI  - The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against
      hepatoblastoma.
AB  - BACKGROUND: The primary goal of current chemotherapy in hepatoblastoma (HB) is
      reduction of tumour volume and vitality to enable complete surgical resection and
      reduce risk of recurrence or metastatic disease. Drug resistance remains a major
      challenge for HB treatment. In some malignancies inhibition of anti-apoptotic
      pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects
      in combination with cystotoxic agents in vitro. Now we analysed toxicology and
      synergistic effects of this approach in HB cells and HB xenografts. METHODS:
      Viability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with
      paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6
      xenotransplants in NOD/LtSz-scid IL2Rgammanull mice (NSG) were treated
      accordingly. Tumour volume and body weight were monitored. Xenografted tumours
      were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay).
      RESULTS: ABT-737 reduced viability in HUH6 and HepT1 cells cultures at
      concentrations above 1 MUM and also enhanced the cytotoxic effect of paclitaxel
      when used in combination. Thereby paclitaxel could be reduced tenfold to achieve
      similar reduction of viability of tumour cells. In contrast no toxicity in
      fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated
      with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the
      beginning of the experiment. However, tumour volume was similar to controls (n =
      5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n =
      8) revealed significantly 10 fold lower relative tumour volumes compared to
      control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this
      mice strain. CONCLUSIONS: Our results demonstrate enhancement of chemotherapy by
      using modulators of apoptosis. Further analyses should include improved
      pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce
      toxicological effects. Sensitising HB to apoptosis may also render resistant HB
      susceptible to established chemotherapy regimens.

PMID- 21854560
TI  - Immunome database for marsupials and monotremes.
AB  - BACKGROUND: To understand the evolutionary origins of our own immune system, we
      need to characterise the immune system of our distant relatives, the marsupials
      and monotremes. The recent sequencing of the genomes of two marsupials (opossum
      and tammar wallaby) and a monotreme (platypus) provides an opportunity to
      characterise the immune gene repertoires of these model organisms. This was
      required as many genes involved in immunity evolve rapidly and fail to be
      detected by automated gene annotation pipelines. DESCRIPTION: We have developed a
      database of immune genes from the tammar wallaby, red-necked wallaby, northern
      brown bandicoot, brush-tail possum, opossum, echidna and platypus. The resource
      contains 2,235 newly identified sequences and 3,197 sequences which had been
      described previously. This comprehensive dataset was built from a variety of
      sources, including EST projects and expert-curated gene predictions generated
      through a variety of methods including chained-BLAST and sensitive HMMER
      searches. To facilitate systems-based research we have grouped sequences based on
      broad Gene Ontology categories as well as by specific functional immune groups.
      Sequences can be extracted by keyword, gene name, protein domain and organism
      name. Users can also search the database using BLAST. CONCLUSION: The Immunome
      Database for Marsupials and Monotremes (IDMM) is a comprehensive database of all
      known marsupial and monotreme immune genes. It provides a single point of
      reference for genomic and transcriptomic datasets. Data from other marsupial and
      monotreme species will be added to the database as it become available. This
      resource will be utilized by marsupial and monotreme immunologists as well as
      researchers interested in the evolution of mammalian immunity.

PMID- 21854562
TI  - Effect of a Herbal-Leucine mix on the IL-1beta-induced cartilage degradation and
      inflammatory gene expression in human chondrocytes.
AB  - BACKGROUND: Conventional treatments for the articular diseases are often
      effective for symptom relief, but can also cause significant side effects and do
      not slow the progression of the disease. Several natural substances have been
      shown to be effective at relieving the symptoms of osteoarthritis (OA), and
      preliminary evidence suggests that some of these compounds may exert a favorable
      influence on the course of the disease. The objective of this study was to
      investigate the anti-inflammatory/chondroprotective potential of a Herbal and
      amino acid mixture containing extract of the Uncaria tomentosa, Boswellia spp.,
      Lepidium meyenii and L-Leucine on the IL-1beta-induced production of nitric oxide
      (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN)
      and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants.
      METHODS: Primary OA chondrocytes or OA cartilage explants were pretreated with
      Herbal-Leucine mixture (HLM, 1-10 MUg/ml) and then stimulated with IL-1beta (5
      ng/ml). Effect of HLM on IL-1beta-induced gene expression of iNOS, MMP-9, MMP-13,
      ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release
      in culture supernatant was done using commercially available kits. RESULTS: HLM
      tested in these in vitro studies was found to be an effective anti-inflammatory
      agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and
      NO production in IL-1beta-stimulated OA chondrocytes (p < 0.05). Supporting these
      gene expression results, IL-1beta-induced cartilage matrix breakdown, as
      evidenced by GAG release from cartilage explants, was also significantly blocked
      (p < 0.05). Moreover, in the presence of herbal-Leucine mixture (HLM) up
      regulation of ACAN and COL2A1 expression in IL-1beta-stimulated OA chondrocytes
      was also noted (p < 0.05). The inhibitory effects of HLM were mediated by
      inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in
      presence of IL-1beta. CONCLUSION: Our data suggests that HLM could be
      chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte
      gene expression from catabolic direction towards anabolic and regenerative, and
      consequently this approach may be potentially useful as a new adjunct
      therapeutic/preventive agent for OA or injury recovery.

PMID- 21854559
TI  - Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight
      into the evolution of mammalian reproduction and development.
AB  - BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus
      eugenii, which is a member of the kangaroo family and the first representative of
      the iconic hopping mammals that symbolize Australia to be sequenced. The tammar
      has many unusual biological characteristics, including the longest period of
      embryonic diapause of any mammal, extremely synchronized seasonal breeding and
      prolonged and sophisticated lactation within a well-defined pouch. Like other
      marsupials, it gives birth to highly altricial young, and has a small number of
      very large chromosomes, making it a valuable model for genomics, reproduction and
      development. RESULTS: The genome has been sequenced to 2 * coverage using Sanger
      sequencing, enhanced with additional next generation sequencing and the
      integration of extensive physical and linkage maps to build the genome assembly.
      We also sequenced the tammar transcriptome across many tissues and developmental
      time points. Our analyses of these data shed light on mammalian reproduction,
      development and genome evolution: there is innovation in reproductive and
      lactational genes, rapid evolution of germ cell genes, and incomplete, locus
      specific X inactivation. We also observe novel retrotransposons and a highly
      rearranged major histocompatibility complex, with many class I genes located
      outside the complex. Novel microRNAs in the tammar HOX clusters uncover new
      potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these
      resources enhance our understanding of marsupial gene evolution, identify
      marsupial-specific conserved non-coding elements and critical genes across a
      range of biological systems, including reproduction, development and immunity,
      and provide new insight into marsupial and mammalian biology and genome
      evolution.

PMID- 21854563
TI  - Providing web-based mental health services to at-risk women.
AB  - BACKGROUND: We examined the feasibility of providing web-based mental health
      services, including synchronous internet video conferencing of an evidence-based
      support/education group, to at-risk women, specifically poor lone mothers. The
      objectives of this study were to: (i) adapt a face-to-face support/education
      group intervention to a web-based format for lone mothers, and (ii) evaluate lone
      mothers' response to web-based services, including an online video conferencing
      group intervention program. METHODS: Participating mothers were recruited through
      advertisements. To adapt the face-to-face intervention to a web-based format, we
      evaluated participant motivation through focus group/key informant interviews (n
      = 7), adapted the intervention training manual for a web-based environment and
      provided a computer training manual. To evaluate response to web-based services,
      we provided the intervention to two groups of lone mothers (n = 15). Pre-post
      quantitative evaluation of mood, self-esteem, social support and parenting was
      done. Post intervention follow up interviews explored responses to the group and
      to using technology to access a health service. Participants received $20 per
      occasion of data collection. Interviews were taped, transcribed and content
      analysis was used to code and interpret the data. Adherence to the intervention
      protocol was evaluated. RESULTS: Mothers participating in this project
      experienced multiple difficulties, including financial and mood problems. We
      adapted the intervention training manual for use in a web-based group environment
      and ensured adherence to the intervention protocol based on viewing
      videoconferencing group sessions and discussion with the leaders. Participant
      responses to the group intervention included decreased isolation, and increased
      knowledge and confidence in themselves and their parenting; the responses closely
      matched those of mothers who obtained same service in face-to-face groups. Pre
      and post-group quantitative evaluations did not show significant improvements on
      measures, although the study was not powered to detect these. CONCLUSIONS: We
      demonstrated that an evidence-based group intervention program for lone mothers
      developed and evaluated in face-to-face context transferred well to an online
      video conferencing format both in terms of group process and outcomes.

PMID- 21854561
TI  - Reduction of neutrophil activity decreases early microvascular injury after
      subarachnoid haemorrhage.
AB  - BACKGROUND: Subarachnoid haemorrhage (SAH) elicits rapid pathological changes in
      the structure and function of parenchymal vessels (<= 100 MUm). The role of
      neutrophils in these changes has not been determined. This study investigates the
      role of neutrophils in early microvascular changes after SAH METHOD: Rats were
      either untreated, treated with vinblastine or anti-polymorphonuclear (PMN) serum,
      which depletes neutrophils, or treated with pyrrolidine dithiocarbamate (PDTC),
      which limits neutrophil activity. SAH was induced by endovascular perforation.
      Neutrophil infiltration and the integrity of vascular endothelium and basement
      membrane were assessed immunohistochemically. Vascular collagenase activity was
      assessed by in situ zymography. RESULTS: Vinblastine and anti-PMN serum reduced
      post-SAH accumulation of neutrophils in cerebral vessels and in brain parenchyma.
      PDTC increased the neutrophil accumulation in cerebral vessels and decreased
      accumulation in brain parenchyma. In addition, each of the three agents decreased
      vascular collagenase activity and post-SAH loss of vascular endothelial and
      basement membrane immunostaining. CONCLUSIONS: Our results implicate neutrophils
      in early microvascular injury after SAH and indicate that treatments which reduce
      neutrophil activity can be beneficial in limiting microvascular injury and
      increasing survival after SAH.

PMID- 21854565
TI  - Hypocellular scar formation or aberrant fibrosis induced by an intrastromal
      corneal ring: a case report.
AB  - INTRODUCTION: Intrastromal corneal rings or segments are approved for the
      treatment of myopia and astigmatism associated with keratoconus. We describe a
      clinicopathological case of intrastromal corneal rings. For the first time, the
      molecular pathological findings of intrastromal corneal rings in the cornea are
      illustrated. CASE PRESENTATION: A 47-year-old African-American man with a history
      of keratoconus and failure in using a Rigid Gas Permeable contact lens received
      an intrastromal corneal ring implant in his left eye. Due to complications,
      penetrating keratoplasty was performed. The intrastromal corneal ring channels
      were surrounded by a dense acellular (channel haze) and/or hypocellular
      (acidophilic densification) collagen scar and slightly edematous keratocytes.
      Mild macrophage infiltration was found near the inner aspect of the intrastromal
      corneal rings. Molecular analyses of the microdissected cells surrounding the
      intrastromal corneal ring channels and central corneal stroma revealed 10 times
      lower relative expression of IP-10/CXCL10 mRNA and two times higher CCL5 mRNA in
      the cells surrounding the intrastromal corneal ring, as compared to the central
      corneal stroma. IP-10/CXCL10 is a fibrotic and angiostatic chemokine produced by
      macrophages, endothelial cells and fibroblasts. CONCLUSION: An intrastromal
      corneal ring implant can induce hypocellular scar formation and mild
      inflammation, which may result from aberrant release of fibrosis-related
      chemokines.

PMID- 21854564
TI  - Secretory glands in cercaria of the neuropathogenic schistosome Trichobilharzia
      regenti - ultrastructural characterization, 3-D modelling, volume and pH
      estimations.
AB  - BACKGROUND: Cercariae of schistosomes employ bioactive molecules for penetration
      into their hosts. These are released from specialized unicellular glands upon
      stimuli from host skin. The glands were previously well-described in the human
      pathogen Schistosoma mansoni. As bird schistosomes can also penetrate human skin
      and cause cercarial dermatitis, our aim was to characterize the architecture and
      ultrastructure of glands in the neurotropic bird schistosome Trichobilharzia
      regenti and compare it with S. mansoni. In the context of different histolytic
      enzymes used by these two species, we focused also on the estimations of gland
      volumes and pH in T. regenti. RESULTS: The architecture and 3-D models of two
      types of acetabular penetration glands, their ducts and of the head gland are
      shown here. We characterized secretory vesicles in all three gland types by means
      of TEM and confirmed accuracy of the models obtained by confocal microscopy. The
      results of two independent approaches showed that the glands occupy ca. one third
      of cercarial body volume (postacetabular glands ca. 15%, circumacetabular 12% and
      head gland 6%). The inner environment within the two types of acetabular glands
      differed significantly as evidenced by dissimilar ability to bind fluorescent
      markers and by pH value which was higher in circumacetabular (7.44) than in
      postacetabular (7.08) glands. CONCLUSIONS: As far as we know, this is the first
      presentation of a 3-D model of cercarial glands and the first exact estimation of
      the volumes of the three gland types in schistosomes. Our comparisons between T.
      regenti and S. mansoni implied that the architecture and ultrastructure of the
      glands is most likely conserved within the family. Only minor variations were
      found between the two species. It seems that the differences in molecular
      composition have no effect on general appearance of the secretory cells in TEM.
      Fluorescent markers employed in this study, distinguishing between secretory
      vesicles and gland types, can be useful in further studies of mechanisms used by
      cercariae for host invasion. Results of the first attempts to estimate pH within
      schistosome glands may help further understanding of regulation of enzymatic
      activities present within the glands.

PMID- 21854566
TI  - Multiarticular chronic tophaceous gout with severe and multiple ulcerations: a
      case report.
AB  - INTRODUCTION: Gout is a common inflammatory arthritis caused by articular
      precipitation of monosodium urate crystals. It usually affects the first
      metatarsophalangeal joint of the foot and less commonly other joints, such as
      wrists, elbows, knees and ankles. CASE PRESENTATION: We report the case of a 75
      year-old Caucasian man with tophaceous multiarticular gout, soft-tissue
      involvement and ulcerated tophi on the first metatarsophalangeal joint of the
      left foot, on the first interphalangeal joint of the right foot and on the left
      thumb. CONCLUSION: Ulcers due to tophaceous gout are currently uncommon
      considering the positive effect of pharmaceutical treatment in controlling
      hyperuricemia. Surgical treatment is seldom required for gout and is usually
      reserved for cases of recurrent attacks with deformities, severe pain, infection
      and joint destruction.

PMID- 21854567
TI  - Prognosis of West Nile virus associated acute flaccid paralysis: a case series.
AB  - INTRODUCTION: Little is known about the long-term health related quality of life
      outcomes in patients with West Nile virus associated acute flaccid paralysis. We
      describe the quality of life scores of seven patients with acute flaccid
      paralysis who presented to hospital between 2003 and 2006, and were followed for
      up to two years. CASE PRESENTATIONS: Between 2003 and 2006, 157 symptomatic
      patients with West Nile virus were enrolled in a longitudinal cohort study of
      West Nile virus in Canada. Seven patients (4%) had acute flaccid paralysis. The
      first patient was a 55-year-old man who presented with left upper extremity
      weakness. The second patient was a 54-year-old man who presented with bilateral
      upper extremity weakness. The third patient was a 66-year-old woman who developed
      bilateral upper and lower extremity weakness. The fourth patient was a 67-year
      old man who presented with right lower extremity weakness. The fifth patient was
      a 60-year-old woman who developed bilateral lower extremity weakness. The sixth
      patient was a 71-year-old man with a history of Parkinson's disease and acute
      onset bilateral lower extremity weakness. The seventh patient was a 52-year-old
      man who presented with right lower extremity weakness. All were Caucasian.
      Patients were followed for a mean of 1.1 years. At the end of follow-up the mean
      score on the Physical Component Summary of the Short-Form 36 scale had only
      slightly increased to 39. In contrast, mean score on the Mental Component Summary
      of the Short-Form 36 scale at the end of follow-up had normalized to 50.
      CONCLUSION: Despite the poor physical prognosis for patients with acute flaccid
      paralysis, the mental health outcomes are generally favorable.

PMID- 21854569
TI  - Squamous cell carcinoma (Marjolin's ulcer) in an orocutaneous fistula of a large
      mandibular ameloblastoma: a case report.
AB  - INTRODUCTION: Ameloblastomas are rare lesions constituting 1% of all jaw tumors.
      Oral squamous cell carcinomas are common lesions; these constitute about 90% of
      all oral cancers. Concurrent tumors consisting of ameloblastoma and squamous cell
      carcinoma are extremely rare. CASE PRESENTATION: This case report describes a 35
      year-old African man who presented with a large mandibular tumor with an
      orocutaneous fistula that was found to be an ameloblastoma on histopathological
      examination, with concurrent squamous cell carcinoma histology within the
      fistula. This presentation was consistent with a Marjolin's ulcer within an
      ameloblastoma. CONCLUSION: Ameloblastomas and Marjolin's ulcers require different
      management strategies. Careful histopathological examination of surgical
      specimens is key to patient outcome, as treatment of these patients depends on an
      accurate diagnosis.

PMID- 21854570
TI  - Scope of claim coverage in patents of fufang Chinese herbal drugs: Substitution
      of ingredients.
AB  - Herbal ingredients in a Chinese fufang prescription are often replaced by one or
      several other herbal combinations. As there have been very few Chinese herbal
      patent infringement cases, it is still unclear how the Doctrine of Equivalents
      should be applied to determine the scope of 'equivalents' in Chinese fufang
      prescriptions. Case law principles from cases in other technical areas such as
      chemical patents and biological drug patents can be borrowed to ascertain a
      precise scope of a fufang patent. This article summarizes and discusses several
      chemical and biopharmaceutical patent cases. In cases where a certain herbal
      ingredient is substituted by another herb or a combination of herbs, accused
      infringers are likely to relate herbal drug patents to chemical drug patents with
      strict interpretation whereas patent owners may take advantage of the liberal
      application of Doctrine of Equivalence in biopharmaceutical patents by
      analogizing the complex nature of herbal drugs with biological drugs. Therefore,
      consideration should be given to the purpose of an ingredient in a patent, the
      qualities when combined with the other ingredients and the intended function. The
      scope of equivalents also depends on the stage of the prior art. Moreover, it is
      desirable to disclose any potential substitutes when drafting the application.
      Claims should be drafted in such a way that all foreseeable modifications are
      encompassed for the protection of the patent owner's intellectual property.

PMID- 21854568
TI  - Mice lacking caspase-2 are protected from behavioral changes, but not pathology,
      in the YAC128 model of Huntington disease.
AB  - BACKGROUND: Huntington Disease (HD) is a neurodegenerative disorder in which
      caspase activation and cleavage of substrates, including the huntingtin protein,
      has been invoked as a pathological mechanism. Specific changes in caspase-2
      (casp2) activity have been suggested to contribute to the pathogenesis of HD,
      however unique casp2 cleavage substrates have remained elusive. We thus utilized
      mice completely lacking casp2 (casp2-/-) to examine the role played by casp2 in
      the progression of HD. This 'substrate agnostic' approach allows us to query the
      effect of casp2 on HD progression without pre-defining proteolytic substrates of
      interest. RESULTS: YAC128 HD model mice lacking casp2 show protection from well
      validated motor and cognitive features of HD, including performance on rotarod,
      swimming T-maze, pre-pulse inhibition, spontaneous alternation and locomotor
      tasks. However, the specific pathological features of the YAC128 mice including
      striatal volume loss and testicular degeneration are unaltered in mice lacking
      casp2. The application of high-resolution magnetic resonance imaging (MRI)
      techniques validates specific neuropathology in the YAC128 mice that is not
      altered by ablation of casp2. CONCLUSIONS: The rescue of behavioral phenotypes in
      the absence of pathological improvement suggests that different pathways may be
      operative in the dysfunction of neural circuitry in HD leading to behavioral
      changes compared to the processes leading to cell death and volume loss.
      Inhibition of caspase-2 activity may be associated with symptomatic improvement
      in HD.

PMID- 21854572
TI  - Accuracy of perfusion MRI with high spatial but low temporal resolution to assess
      invasive breast cancer response to neoadjuvant chemotherapy: a retrospective
      study.
AB  - BACKGROUND: To illustrate that Breast-MRI performed in high spatial resolution
      and low temporal resolution (1 minute) allows the measurement of kinetic
      parameters that can assess the final pathologic response to neoadjuvant
      chemotherapy in breast cancer. METHODS: Breast-MRI was performed in 24 women
      before and after treatment. Eight series of 1.11 minute-duration were acquired
      with a sub-millimeter spatial resolution. Transfer constant (K(trans)) and
      leakage space (V(e)) were calculated using measured and theoretical Arterial
      Input Function (AIF). Changes in kinetic parameters after treatment obtained with
      both AIFs were compared with final pathologic response graded in non-responder (<
      50% therapeutic effect), partial-responder (> 50% therapeutic effect) and
      complete responder. Accuracies to identify non-responders were compared with
      receiver operating characteristic curves. RESULTS: With measured-AIF, changes in
      kinetic parameters measured after treatment were in agreement with the final
      pathological response. Changes in V(e) and K(trans) were significantly different
      between non-(N = 11), partial-(N = 7), and complete (N = 6) responders, (P =
      0.0092 and P = 0.0398 respectively). A decrease in V(e) of more than -72% and
      more than -84% for K(trans) resulted in 73% sensitivity for identifying non
      responders (specificity 92% and 77% respectively). A decrease in V(e) of more
      than -87% helped to identify complete responders (Sensitivity 89%, Specificity
      83%). With theoretical-AIF, changes in kinetic parameters had lower accuracy.
      CONCLUSION: There is a good agreement between pathological findings and changes
      in kinetic parameters obtained with breast-MRI in high spatial and low temporal
      resolution when measured-AIF is used. Further studies are necessary to confirm
      whether MRI contrast kinetic parameters can be used earlier as a response
      predictor to neoadjuvant chemotherapy.

PMID- 21854571
TI  - Apolipoprotein A1/C3/A5 haplotypes and serum lipid levels.
AB  - BACKGROUND: The association of single nucleotide polymorphisms (SNPs) in the
      apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is
      inconsistent. The present study was undertaken to detect the association between
      the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels
      in the general Chinese population. METHODS: A total of 1030 unrelated subjects
      (492 males and 538 females) aged 15-89 were randomly selected from our previous
      stratified randomized cluster samples. Genotyping of the ApoA1 -75 bp G>A, ApoC3
      3238C>G, ApoA5 -1131T>C, ApoA5 c.553G>T and ApoA5 c.457G>A was performed by
      polymerse chain reaction and restriction fragment length polymorphism combined
      with gel electrophoresis, and then confirmed by direct sequencing. Pair-wise
      linkage disequilibria and haplotype analysis among the five SNPs were estimated.
      RESULTS: The levels of high-density lipoprotein cholesterol (HDL-C) and ApoA1
      were lower in males than in femailes (P < 0.05 for each). The allelic and
      genotypic frequencies of the SNPs were no significant difference between males
      and females except ApoC3 3238C>G. There were 11 haplotypes with a frequency >1%
      identified in the cluster in our population. At the global level, the haplotypes
      comprised of all five SNPs were significantly associated with all seven lipid
      traits. In particular, haplotype G-G-C-C-A (6%; in the order of ApoA5 c.553G>T,
      ApoA5 c.457G>A, ApoA5 -1131T>C, ApoC3 3238C>G, and ApoA1 -75bp G>A) and G-A-T-C-G
      (4%) showed consistent association with total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and the ApoA1/ApoB ratio. In
      addition, carriers of haplotype G-G-T-C-G (26%) had increased serum concentration
      of HDL-C and ApoA1, whereas carriers of G-G-C-G-G (15%) had high concentrations
      of TC, triglyceride (TG) and ApoB. We also found that haplotypes with five SNPs
      explain much more serum lipid variation than any single SNP alone, especially for
      TG (4.4% for haplotype vs. 2.4% for -1131T>C max based on R-square) and HDL-C
      (5.1% for haplotype vs. 0.9% for c.553G>T based on R-square). Serum lipid
      parameters were also correlated with genotypes and several environment factors.
      CONCLUSIONS: Several common SNPs and their haplotypes in the ApoA1/C3/A5 gene
      cluster are closely associated with modifications of serum lipid parameters in
      the general Chinese population.

PMID- 21854573
TI  - Characterisation of marsupial PHLDA2 reveals eutherian specific acquisition of
      imprinting.
AB  - BACKGROUND: Genomic imprinting causes parent-of-origin specific gene expression
      by differential epigenetic modifications between two parental genomes. We
      previously reported that there is no evidence of genomic imprinting of CDKN1C in
      the KCNQ1 domain in the placenta of an Australian marsupial, the tammar wallaby
      (Macropus eugenii) whereas tammar IGF2 and H19, located adjacent to the KCNQ1
      domain in eutherian mammals, are imprinted. We have now identified and
      characterised the marsupial orthologue of PHLDA2, another gene in the KCNQ1
      domain (also known as IPL or TSSC3) that is imprinted in eutherians. In mice,
      Phlda2 is a dose-sensitive negative regulator of placental growth, as Cdkn1c is
      for embryonic growth. RESULTS: Tammar PHLDA2 is highly expressed in the yolk sac
      placenta compared to other fetal tissues, confirming a similar expression pattern
      to that of mouse Phlda2. However, tammar PHLDA2 is biallelically expressed in
      both the fetus and yolk sac placenta, so it is not imprinted. The lack of
      imprinting in tammar PHLDA2 suggests that the acquisition of genomic imprinting
      of the KCNQ1 domain in eutherian mammals, accompanied with gene dosage reduction,
      occurred after the split of the therian mammals into the marsupials and
      eutherians. CONCLUSIONS: Our results confirm the idea that acquisition of genomic
      imprinting in the KCNQ1 domain occurred specifically in the eutherian lineage
      after the divergence of marsupials, even though imprinting of the adjacent IGF2
      H19 domain arose before the marsupial-eutherian split. These data are consistent
      with the hypothesis that genomic imprinting of the KCNQ1 domain may have
      contributed to the evolution of more complex placentation in the eutherian
      lineage by reduction of the gene dosage of negative regulators for both embryonic
      and placental growth.

PMID- 21854574
TI  - Identification of two distinct genes at the vertebrate TRPC2 locus and their
      characterisation in a marsupial and a monotreme.
AB  - BACKGROUND: The vomeronasal organ (VNO) detects pheromones via two large families
      of vomeronasal receptors: vomeronasal receptor 1 (V1R) and vomeronasal receptor 2
      (V2R). Both VRs have a common receptor activation cascade involving transient
      receptor potential channel, subfamily C, member 2 (TRPC2). RESULTS: We
      characterised the TRPC2 locus in a marsupial, the tammar wallaby (Macropus
      eugenii), and identified two independently regulated genes not previously
      recognised as distinct. 3'-located exons comprise bona fide TRPC2 whilst 5'
      located exons, previously identified as part of TRPC2, comprise a distinct gene,
      which we term XNDR (XRCC1 N-terminal domain-related). The two genes show
      contrasting expression patterns in the tammar: TRPC2 is specifically expressed in
      adult and developing VNO, whereas XNDR is widely expressed in many tissues
      suggesting a non-VNO-specific role. Strong expression of TRPC2 was detected only
      after about day 30 post-partum, suggesting that the VNO may not be functional
      during early pouch life of the tammar. Similarly restricted expression of TRPC2
      and widespread expression of XNDR was also detected in the platypus.
      Bioinformatic analysis of the genomes of a wide range of species suggests that
      the identity of XNDR and TRPC2 as distinct genes is conserved among vertebrates.
      Finally, we analysed the promoter of mammalian TRPC2 and identified a conserved
      binding site for NHLH1, a transcription factor previously implicated in VNO
      receptor neuron development. CONCLUSIONS: Two functionally distinct vertebrate
      genes-XNDR and TRPC2 - occupy a genomic locus that was previously defined as a
      single gene in the mouse. The former is widely expressed with a putative role in
      DNA repair, while the latter shows VNO-specific expression under the probable
      regulation of NHLH1.

PMID- 21854575
TI  - Repeatability and validity of a standardised maximal step-up test for leg
      function--a diagnostic accuracy study.
AB  - BACKGROUND: Objectively assessed physical performance is a strong predictor for
      morbidity and premature death and there is an increasing interest in the role of
      sarcopenia in many chronic diseases. There is a need for robust and valid
      functional tests in clinical practice. Therefore, the repeatability and validity
      of a newly developed maximal step up test (MST) was assessed. METHODS: The MST,
      assessing maximal step-up height (MSH) in 3-cm increments, was evaluated in 60
      healthy middle-aged subjects, 30 women and 30 men. The repeatability of MSH and
      the correlation between MSH and isokinetic knee extension peak torque (IKEPT),
      self-reported physical function (SF-36, PF), patient demographics and self
      reported physical activity were investigated. RESULTS: The repeatability between
      occasions and between testers was 6 cm. MSH (range 12-45 cm) was significantly
      correlated to IKEPT, (r = 0.68, P < 0.001), SF-36 PF score, (r = 0.29, P = 0.03),
      sex, age, weight and BMI. The results also show that MSH above 32 cm
      discriminates subjects in our study with no limitation in self-reported physical
      function. CONCLUSIONS: The standardised MST is considered a reliable leg function
      test for clinical practice. The MSH was related to knee extension strength and
      self-reported physical function. The precision of the MST for identification of
      limitations in physical function needs further investigation.

PMID- 21854576
TI  - How do COPD patients respond to exacerbations?
AB  - BACKGROUND: Although timely treatment of COPD exacerbations seems clinically
      important, nearly half of these exacerbations remain unreported and subsequently
      untreated. Recent studies have investigated incidence and impact of failure to
      seek medical treatment during exacerbations. Yet, little is known about type and
      timing of other self-management actions in periods of symptom deterioration. The
      current prospective study aims at determining the relative incidence, timing and
      determinants of three types of patient responses. METHODS: In a multicentre
      observational study, 121 patients (age 67 +/- 11 years, FEV1pred. 48 +/- 19) were
      followed for 6 weeks by daily diary symptom recording. Three types of action were
      assessed daily: planning periods of rest, breathing techniques and/or sputum
      clearing (type-A), increased bronchodilator use (type-B) and contacting a
      healthcare provider (type-C). RESULTS: Type-A action was taken in 70.7%, type-B
      in 62.7% and type C in 17.3% of exacerbations (n = 75). Smokers were less likely
      to take type-A and B actions. Type-C actions were associated with more severe
      airflow limitation and increased number of hospital admissions in the last year.
      CONCLUSIONS: Our study shows that most patients are willing to take timely self
      management actions during exacerbations. Future research is needed to determine
      whether the low incidence of contacting a healthcare provider is due to a lack of
      self-management or healthcare accessibility.

PMID- 21854577
TI  - Kyphoplasty in osteoporotic vertebral compression fractures--guidelines and
      technical considerations.
AB  - Osteoporotic vertebral compression fractures are a menace to the elderly
      generation causing diminished quality of life due to pain and deformity. At
      first, conservative treatment still is the method of choice. In case of resulting
      deformity, sintering and persistent pain vertebral cement augmentation techniques
      today are widely used. Open correction of resulting deformity by different types
      of osteotomies addresses sagittal balance, but has comparably high morbidity.
      Besides conventional vertebral cement augmentation techniques balloon kyphoplasty
      has become a popular tool to address painful thoracic and lumbar compression
      fractures. It showed improved pain reduction and lower complication rates
      compared to standard vertebroplasty. Interestingly the results of two placebo
      controlled vertebroplasty studies question the value of cement augmentation, if
      compared to a sham operation. Even though there exists now favourable data for
      kyphoplasty from one randomised controlled trial, the absence of a sham group
      leaves the placebo effect unaddressed. Technically kyphoplasty can be performed
      with a transpedicular or extrapedicular access. Polymethyl methacrylate (PMMA)
      cement should be favoured, since calcium phosphate cement showed inferior
      biomechanical properties and less effect on pain reduction especially in less
      stable burst fractures. Common complications of kyphoplasty are cement leakage
      and adjacent segment fractures. Rare complications are toxic PMMA-monomer
      reactions, cement embolisation, and infection.

PMID- 21854578
TI  - High degree of polarization of the near-band-edge photoluminescence in ZnO
      nanowires.
AB  - We investigated the polarization dependence of the near-band-edge
      photoluminescence in ZnO strain-free nanowires grown by vapor phase technique.
      The emission is polarized perpendicular to the nanowire axis with a large
      polarization ratio (as high as 0.84 at 4.2 K and 0.63 at 300 K). The observed
      polarization ratio is explained in terms of selection rules for excitonic
      transitions derived from the k.p theory for ZnO. The temperature dependence of
      the polarization ratio evidences a gradual activation of the XC excitonic
      transition.PACS: 78.55.Cr, 77.22.Ej, 81.07.Gf.

PMID- 21854579
TI  - The resistance of the yeast Saccharomyces cerevisiae to the biocide
      polyhexamethylene biguanide: involvement of cell wall integrity pathway and
      emerging role for YAP1.
AB  - BACKGROUND: Polyhexamethylene biguanide (PHMB) is an antiseptic polymer that is
      mainly used for cleaning hospitals and pools and combating Acantamoeba infection.
      Its fungicide activity was recently shown by its lethal effect on yeasts that
      contaminate the industrial ethanol process, and on the PE-2 strain of
      Saccharomyces cerevisiae, one of the main fermenting yeasts in Brazil. This
      pointed to the need to know the molecular mechanism that lay behind the cell
      resistance to this compound. In this study, we examined the factors involved in
      PHMB-cell interaction and the mechanisms that respond to the damage caused by
      this interaction. To achieve this, two research strategies were employed: the
      expression of some genes by RT-qPCR and the analysis of mutant strains. RESULTS:
      Cell Wall integrity (CWI) genes were induced in the PHMB-resistant Saccharomyces
      cerevisiae strain JP-1, although they are poorly expressed in the PHMB-sensitive
      Saccharomyces cerevisiae PE2 strain. This suggested that PHMB damages the glucan
      structure on the yeast cell wall. It was also confirmed by the observed
      sensitivity of the yeast deletion strains, Deltaslg1, Deltarom2, Deltamkk2,
      Deltaslt2, Deltaknr4, Deltaswi4 and Deltaswi4, which showed that the protein
      kinase C (PKC) regulatory mechanism is involved in the response and resistance to
      PHMB. The sensitivity of the Deltahog1 mutant was also observed. Furthermore, the
      cytotoxicity assay and gene expression analysis showed that the part played by
      YAP1 and CTT1 genes in cell resistance to PHMB is unrelated to oxidative stress
      response. Thus, we suggested that Yap1p can play a role in cell wall maintenance
      by controlling the expression of the CWI genes. CONCLUSION: The PHMB treatment of
      the yeast cells activates the PKC1/Slt2 (CWI) pathway. In addition, it is
      suggested that HOG1 and YAP1 can play a role in the regulation of CWI genes.

PMID- 21854580
TI  - Cocaine Addiction Treatments to improve Control and reduce Harm (CATCH): new
      pharmacological treatment options for crack-cocaine dependence in the
      Netherlands.
AB  - BACKGROUND: Cocaine, particularly in its base form ('crack'), has become one of
      the drugs of most concern in the Netherlands, being associated with a wide range
      of medical, psychiatric and social problems for the individual, and with
      significant public order consequences for society. Available treatment options
      for cocaine dependent users are limited, and a substantial part of the cocaine
      dependent population is not reached by the addiction treatment system.
      Psychosocial interventions for cocaine dependence generally show modest results,
      and there are no registered pharmacological treatments to date, despite the wide
      range of medications tested for this type of dependence. The present study
      (Cocaine Addiction Treatments to improve Control and reduce Harm; CATCH)
      investigates the possibilities and problems associated with new pharmacological
      treatments for crack dependent patients. METHODS/DESIGN: The CATCH-study consists
      of three separate randomised controlled, open-label, parallel-group feasibility
      trials, conducted at three separate addiction treatment institutes in the
      Netherlands. Patients are either new referrals or patients already in treatment.
      A total of 216 eligible outpatients are randomised using pre-randomisation double
      consent design and receive either 12 weeks treatment with oral topiramate (n =
      36; Brijder Addiction Treatment, The Hague), oral modafinil (n = 36; Arkin,
      Amsterdam), or oral dexamphetamine sustained-release (n = 36; Bouman GGZ,
      Rotterdam) as an add-on to cognitive behavioural therapy (CBT), or receive a 12
      week CBT only (controls: n = 3 * 36). Primary outcome in these feasibility trials
      is retention in the underlying psychosocial treatment (CBT). Secondary outcomes
      are acceptance and compliance with the study medication, safety, changes in
      cocaine (and other drug) use, physical and mental health, social functioning, and
      patient satisfaction. DISCUSSION: To date, the CATCH-study is the first study in
      the Netherlands that explores new treatment options for crack-cocaine dependence
      focusing on both abstinence and harm minimisation. It is expected that the study
      will contribute to the development of new treatments for one of the most
      problematic substance use disorders. TRIAL REGISTRATION: The Netherlands National
      Trial Register NTR2576The European Union Drug Regulating Authorities Clinical
      Trials EudraCT2009-010584-16.

PMID- 21854581
TI  - Differential strengths of selection on S-RNases from Physalis and Solanum
      (Solanaceae).
AB  - BACKGROUND: The S-RNases of the Solanaceae are highly polymorphic self
      incompatibility (S-) alleles subject to strong balancing selection. Relatively
      recent diversification of S-alleles has occurred in the genus Physalis following
      a historical restriction of S-allele diversity. In contrast, the genus Solanum
      did not undergo a restriction of S-locus diversity and its S-alleles are
      generally much older. Because recovery from reduced S-locus diversity should
      involve increased selection, we employ a statistical framework to ask whether S
      locus selection intensities are higher in Physalis than Solanum. Because
      different S-RNase lineages diversify in Physalis and Solanum, we also ask whether
      different sites are under selection in different lineages. RESULTS: Maximum
      likelihood and Bayesian coalescent methods found higher intensities of selection
      and more sites under significant positive selection in the 48 Physalis S-RNase
      alleles than the 49 from Solanum. Highest posterior densities of dN/dS (omega)
      estimates show that the strength of selection is greater for Physalis at 36
      codons. A nested maximum likelihood method was more conservative, but still found
      16 sites with greater selection in Physalis. Neither method found any codons
      under significantly greater selection in Solanum. A random effects likelihood
      method that examines data from both taxa jointly confirmed higher selection
      intensities in Physalis, but did not find different proportions of sites under
      selection in the two datasets. The greatest differences in strengths of selection
      were found in the most variable regions of the S-RNases, as expected if these
      regions encode self-recognition specificities. Clade-specific likelihood models
      indicated some codons were under greater selection in background Solanum lineages
      than in specific lineages of Physalis implying that selection on sites may differ
      among lineages. CONCLUSIONS: Likelihood and Bayesian methods provide a
      statistical approach to testing differential selection across populations or
      species. These tests appear robust to the levels of polymorphism found in diverse
      S-allele collections subject to strong balancing selection. As predicted, the
      intensity of selection at the S-locus was higher in the taxon with more recent S
      locus diversification. This is the first confirmation by statistical test of
      differing selection intensities among self-incompatibility alleles from different
      populations or species.

PMID- 21854582
TI  - Differentiation of mouse bone marrow derived stem cells toward microglia-like
      cells.
AB  - BACKGROUND: Microglia, the macrophages of the brain, have been implicated in the
      causes of neurodegenerative diseases and display a loss of function during aging.
      Throughout life, microglia are replenished by limited proliferation of resident
      microglial cells. Replenishment by bone marrow-derived progenitor cells is still
      under debate. In this context, we investigated the differentiation of mouse
      microglia from bone marrow (BM) stem cells. Furthermore, we looked at the effects
      of FMS-like tyrosine kinase 3 ligand (Flt3L), astrocyte-conditioned medium (ACM)
      and GM-CSF on the differentiation to microglia-like cells. METHODS: We assessed
      in vitro-derived microglia differentiation by marker expression (CD11b/CD45,
      F4/80), but also for the first time for functional performance (phagocytosis,
      oxidative burst) and in situ migration into living brain tissue. Integration,
      survival and migration were assessed in organotypic brain slices. RESULTS: The
      cells differentiated from mouse BM show function, markers and morphology of
      primary microglia and migrate into living brain tissue. Flt3L displays a negative
      effect on differentiation while GM-CSF enhances differentiation. CONCLUSION: We
      conclude that in vitro-derived microglia are the phenotypic and functional
      equivalents to primary microglia and could be used in cell therapy.

PMID- 21854583
TI  - Prevalence and antimicrobial resistance of Salmonella isolated from lactating
      cows and in contact humans in dairy farms of Addis Ababa: a cross sectional
      study.
AB  - BACKGROUND: Salmonella are the major pathogenic bacteria in humans as well as in
      animals. Salmonella species are leading causes of acute gastroenteritis in
      several countries and salmonellosis remains an important public health problem
      worldwide, particularly in the developing countries. The situation is more
      aggravated by the ever increasing rate of antimicrobial resistance strains.
      Cattle have been implicated as a source of human infection with antimicrobial
      resistant Salmonella through direct contact with livestock and through the
      isolation of antimicrobial resistant Salmonella from raw milk, cheddar cheese,
      and hamburger meat traced to dairy farms. Despiite the presence of many studies
      on the prevalence and antimicrobial susceptibility pattern of Salmonella in
      Ethiopia, nothing has been said on the degree of the situation among apparently
      healthy lactating cows and in contact humans. Hence this study was conducted to
      determine the prevalence and antimicrobial resistance pattern of Salmonella
      isolates from lactating cows and in contact humans in dairy farms of Addis Ababa.
      METHODS: a cross sectional study was conducted in Addis Ababa by collecting milk
      and faecal samples from lactating cows and stool samples from humans working in
      dairy farms. Samples were pre-enriched in buffered peptone water followed by
      selective enrichment using selenite cysteine and Rapaport-Vassilidis broths.
      Isolation and identification was made by inoculating the selectively enriched
      sample on to Xylose Lysine Deoxycholate agar followed by confirmation of
      presumptive colonies using different biochemical tests. The Kibry Bauer disk
      diffusion method was used for antimicrobial sensitivity testing. RESULTS: 10.7%
      (21/195) of cows and 13.6% (3/22) of the human subjects sheded Salmonella. 83%
      resistance to two or more antimicrobials and 100% resistance to ampicillin were
      observed. Most of the isolates were relatively sensitive to ciprofloxacin,
      cotrimoxazole, and chloramphenicol. CONCLUSION: High proportion of Salmonella
      isolates developed resistance to the commonly prescribed antimicrobials and this
      may be a considerable risk in the treatment of clinical cases. So, wise use of
      antimicrobials must be practiced to combat the ever increasing situation of
      antimicrobial resistance.

PMID- 21854584
TI  - Effect of an expansion in private sector provision of contraceptive supplies on
      horizontal inequity in modern contraceptive use: evidence from Africa and Asia.
AB  - BACKGROUND: One strategic approach available to policy makers to improve the
      availability of reproductive and child health care supplies and services as well
      as the sustainability of programs is to expand the role of the private sector in
      providing these services. However, critics of this approach argue that increased
      reliance on the private sector will not serve the needs of the poor, and could
      lead to increases in socio-economic disparities in the use of health care
      services. The purpose of this study is to investigate whether the expansion of
      the role of private providers in the provision of modern contraceptive supplies
      is associated with increased horizontal inequity in modern contraceptive use.
      METHODS: The study is based on multiple rounds of Demographic and Health Survey
      data from four selected countries (Nigeria, Uganda, Bangladesh, and Indonesia) in
      which there was an increase in the private sector supply of contraceptives. The
      methodology involves estimating concentration indices to assess the degree of
      inequality and inequity in contraceptive use by wealth groups across time. In
      order to measure inequity in the use of modern contraceptives, the study uses
      multivariate methods to control for differences in the need for family planning
      services in relation to household wealth. RESULTS: The results suggest that the
      expansion of the private commercial sector supply of contraceptives in the four
      study countries did not lead to increased inequity in the use of modern
      contraceptives. In Nigeria and Uganda, inequity actually decreased over time;
      while in Bangladesh and Indonesia, inequity fluctuated. CONCLUSIONS: The study
      results do not offer support to the hypothesis that the increased role of the
      private commercial sector in the supply of contraceptive supplies led to
      increased inequity in modern contraceptive use.

PMID- 21854585
TI  - Guidelines for delineation of lymphatic clinical target volumes for high
      conformal radiotherapy: head and neck region.
AB  - The success of radiotherapy depends on the accurate delineation of the clinical
      target volume. The delineation of the lymph node regions has most impact,
      especially for tumors in the head and neck region. The purpose of this article
      was the development an atlas for the delineation of the clinical target volume
      for patients, who should receive radiotherapy for a tumor of the head and neck
      region. Literature was reviewed for localisations of the adjacent lymph node
      regions and their lymph drain in dependence of the tumor entity. On this basis
      the lymph node regions were contoured on transversal CT slices. The probability
      for involvement was reviewed and a recommendation for the delineation of the CTV
      was generated.

PMID- 21854586
TI  - Degeneration of penicillin production in ethanol-limited chemostat cultivations
      of Penicillium chrysogenum: A systems biology approach.
AB  - BACKGROUND: In microbial production of non-catabolic products such as antibiotics
      a loss of production capacity upon long-term cultivation (for example chemostat),
      a phenomenon called strain degeneration, is often observed. In this study a
      systems biology approach, monitoring changes from gene to produced flux, was used
      to study degeneration of penicillin production in a high producing Penicillium
      chrysogenum strain during prolonged ethanol-limited chemostat cultivations.
      RESULTS: During these cultivations, the biomass specific penicillin production
      rate decreased more than 10-fold in less than 22 generations. No evidence was
      obtained for a decrease of the copy number of the penicillin gene cluster, nor a
      significant down regulation of the expression of the penicillin biosynthesis
      genes. However, a strong down regulation of the biosynthesis pathway of cysteine,
      one of the precursors of penicillin, was observed. Furthermore the protein levels
      of the penicillin pathway enzymes L-alpha-(delta-aminoadipyl)-L-alpha-cystenyl-D
      alpha-valine synthetase (ACVS) and isopenicillin-N synthase (IPNS), decreased
      significantly. Re-cultivation of fully degenerated cells in unlimited batch
      culture and subsequent C-limited chemostats did only result in a slight recovery
      of penicillin production. CONCLUSIONS: Our findings indicate that the observed
      degeneration is attributed to a significant decrease of the levels of the first
      two enzymes of the penicillin biosynthesis pathway, ACVS and IPNS. This decrease
      is not caused by genetic instability of the penicillin amplicon, neither by down
      regulation of the penicillin biosynthesis pathway. Furthermore no indications
      were obtained for degradation of these enzymes as a result of autophagy. Possible
      causes for the decreased enzyme levels could be a decrease of the translation
      efficiency of ACVS and IPNS during degeneration, or the presence of a culture
      variant impaired in the biosynthesis of functional proteins of these enzymes,
      which outcompeted the high producing part of the population.

PMID- 21854587
TI  - The charcoal trap: Miombo forests and the energy needs of people.
AB  - BACKGROUND: This study evaluates the carbon dioxide and other greenhouse gas
      fluxes to the atmosphere resulting from charcoal production in Zambia. It
      combines new biomass and flux data from a study, that was conducted in a miombo
      woodland within the Kataba Forest Reserve in the Western Province of Zambia, with
      data from other studies. RESULTS: The measurements at Kataba compared protected
      area (3 plots) with a highly disturbed plot outside the forest reserve and showed
      considerably reduced biomass after logging for charcoal production. The average
      aboveground biomass content of the reserve (Plots 2-4) was around 150 t ha-1,
      while the disturbed plot only contained 24 t ha-1. Soil carbon was not reduced
      significantly in the disturbed plot. Two years of eddy covariance measurements
      resulted in net ecosystem exchange values of -17 +/- 31 g C m-2 y-1, in the first
      and 90 +/- 16 g C m-2 in the second year. Thus, on the basis of these two years
      of measurement, there is no evidence that the miombo woodland at Kataba
      represents a present-day carbon sink. At the country level, it is likely that
      deforestation for charcoal production currently leads to a per capita emission
      rate of 2 - 3 t CO2 y-1. This is due to poor forest regeneration, although the
      resilience of miombo woodlands is high. Better post-harvest management could
      change this situation. CONCLUSIONS: We argue that protection of miombo woodlands
      has to account for the energy demands of the population. The production at
      national scale that we estimated converts into 10,000 - 15,000 GWh y-1 of energy
      in the charcoal. The term "Charcoal Trap" we introduce, describes the fact that
      this energy supply has to be substituted when woodlands are protected. One
      possible solution, a shift in energy supply from charcoal to electricity, would
      reduce the pressure of forests but requires high investments into grid and power
      generation. Since Zambia currently cannot generate this money by itself, the
      country will remain locked in the charcoal trap such as many other of its African
      neighbours. The question arises whether and how money and technology transfer to
      increase regenerative electrical power generation should become part of a post
      Kyoto process. Furthermore, better inventory data are urgently required to
      improve knowledge about the current state of the woodland usage and recovery. Net
      greenhouse gas emissions could be reduced substantially by improving the post
      harvest management, charcoal production technology and/or providing alternative
      energy supply.

PMID- 21854588
TI  - Minimally invasive computer-navigated total hip arthroplasty, following the
      concept of femur first and combined anteversion: design of a blinded randomized
      controlled trial.
AB  - BACKGROUND: Impingement can be a serious complication after total hip
      arthroplasty (THA), and is one of the major causes of postoperative pain,
      dislocation, aseptic loosening, and implant breakage. Minimally invasive THA and
      computer-navigated surgery were introduced several years ago. We have developed a
      novel, computer-assisted operation method for THA following the concept of "femur
      first"/"combined anteversion", which incorporates various aspects of performing a
      functional optimization of the cup position, and comprehensively addresses range
      of motion (ROM) as well as cup containment and alignment parameters. Hence, the
      purpose of this study is to assess whether the artificial joint's ROM can be
      improved by this computer-assisted operation method. Second, the clinical and
      radiological outcome will be evaluated. METHODS/DESIGN: A registered patient- and
      observer-blinded randomized controlled trial will be conducted. Patients between
      the ages of 50 and 75 admitted for primary unilateral THA will be included.
      Patients will be randomly allocated to either receive minimally invasive computer
      navigated "femur first" THA or the conventional minimally invasive THA procedure.
      Self-reported functional status and health-related quality of life
      (questionnaires) will be assessed both preoperatively and postoperatively.
      Perioperative complications will be registered. Radiographic evaluation will take
      place up to 6 weeks postoperatively with a computed tomography (CT) scan.
      Component position will be evaluated by an independent external institute on a 3D
      reconstruction of the femur/pelvis using image-processing software. Postoperative
      ROM will be calculated by an algorithm which automatically determines bony and
      prosthetic impingements. DISCUSSION: In the past, computer navigation has
      improved the accuracy of component positioning. So far, there are only few
      objective data quantifying the risks and benefits of computer navigated THA.
      Therefore, this study has been designed to compare minimally invasive computer
      navigated "femur first" THA with a conventional technique for minimally invasive
      THA. The results of this trial will be presented as soon as they become
      available. TRIAL REGISTRATION NUMBER: DRKS00000739.

PMID- 21854589
TI  - Developmental expression of p97/VCP (Valosin-containing protein) and Jab1/CSN5 in
      the rat testis and epididymis.
AB  - BACKGROUND: The ubiquitin proteasome system (UPS) is a key player in regulating
      many cellular processes via proteasomal degradation of ubiquitinated proteins.
      Recently published data show that Jab1/CSN5 interacts with p97/VCP and controls
      the ubiquitination status of proteins bound to p97/VCP in mouse and human cells.
      However, coexpression of p97/VCP and Jab1/CSN5 in the developing rat testis and
      epididymis has not previously been studied. METHODS: Testicular and epididymal
      tissues from 5-, 15-, 30-, and 60-day-old rats were examined by
      immunohistochemistry and Western blotting. Colocalisation of proteins was
      determined by immunofluorescence microscopy. RESULTS: In the 5-day-old rat
      testis, p97/VCP and Jab1/CSN5 were specifically expressed in gonocytes. The
      expression of p97/VCP and Jab1/CSN5 significantly increased at day 15 and was
      found in spermatogonia, Sertoli cells and spermatocytes. In 30- and 60-day-old
      rat testes, p97/VCP indicated moderate to strong expression in Sertoli cells,
      spermatogonia, round and elongating spermatids. However, moderate to weak
      expression was observed in spermatocytes. Jab1/CSN5 showed strong expression in
      spermatogonia and spermatocytes, while relatively moderate expression was
      observed in round and elongating spermatids in 30- and 60-day-old rat testes. In
      contrast, in the epididymis, the expression of both proteins gradually increased
      from 5 to 60 days of age. After rats reached 2 weeks of age, the expression of
      both proteins was mostly restricted to the basal and principal cells of the caput
      epididymis. CONCLUSIONS: Our study suggests that p97/VCP and Jab1/CSN5 could be
      an important part of the UPS in the developing rat testis and epididymis and that
      both proteins may be involved in the regulation of spermatogenesis and epididymal
      epithelial functions.

PMID- 21854590
TI  - High content of long-chain n-3 polyunsaturated fatty acids in red blood cells of
      Kenyan Maasai despite low dietary intake.
AB  - BACKGROUND: Increasing land restrictions and a reduced livestock-to-human ratio
      during the 20th century led the Maasai to lead a more sedentary, market
      orientated lifestyle. Although plant-derived food nowadays contributes
      substantially to their diet, dairy products being high in saturated fatty acids
      (SFA) and low in polyunsaturated fatty acids (PUFA) still are an important energy
      source. Since reliable data regarding the Maasai diet date back to the 1980s, the
      study objective was to document current diet practices in a Kenyan Maasai
      community and to investigate the fatty acid distribution in diet and red blood
      cells. METHODS: A cross-sectional study was conducted among 26 Maasai (20 women,
      6 men) from Loodokilani, Kajiado District, Kenya. Food intake was described by
      the subjects via 24-h recall, and both food and blood samples were analysed.
      RESULTS: Two main foods--milk and ugali--constituted the Maasai diet in this
      region. A total of 0.9 L of milk and 0.6 kg of ugali were consumed per person and
      day to yield an energy intake of 7.6 MJ/d per person. A major proportion of
      ingested food contributing 58.3% to the total dietary energy (en%) was plant
      derived, followed by dairy products representing 41.1 en%. Fat consumed (30.5
      en%) was high in SFA (63.8%) and low in PUFA (9.2%). Long-chain n-3 PUFA (EPA,
      DPA and DHA) made up only 0.15% of the ingested fatty acids, but 5.9% of red
      blood cell fatty acids. CONCLUSION: The study indicates the Maasai diet is rich
      in SFA and low in PUFA. Nevertheless, red blood cells are composed of comparable
      proportions of long-chain n-3 PUFA to populations consuming higher amounts of
      this fatty acid group.

PMID- 21854591
TI  - On the protective effect of omega-3 against propionic acid-induced neurotoxicity
      in rat pups.
AB  - BACKGROUNDS: The investigation of the environmental contribution for
      developmental neurotoxicity is very important. Many environmental chemical
      exposures are now thought to contribute to the development of neurological
      disorders, especially in children. Results from animal studies may guide
      investigations of human populations toward identifying environmental contaminants
      and drugs that produce or protect from neurotoxicity and may help in the
      treatment of neurodevelopmental disorders. OBJECTIVE: To study the protective
      effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by
      propionic acid (PPA) in rats. METHODS: 24 young male Western Albino rats were
      enrolled in the present study. They were grouped into three equal groups; oral
      buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day
      for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day
      omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as
      control given only phosphate buffered saline. Tumor necrosis factor-alpha,
      caspase-3, interlukin-6, gamma amino-buteric acid (GABA), serotonin, dopamine and
      phospholipids were then assayed in the rats brain's tissue of different groups.
      RESULTS: The obtained data showed that PPA caused multiple signs of brain
      toxicity as measured by depletion of gamaaminobyteric acid (GABA), serotonin
      (5HT) and dopamine (DA) as three important neurotransmitters that reflect brain
      function. A high significant increase of interlukin-6 (Il-6), tumor necrosis
      factor-alpha (TNF-alpha) as excellent markers of proinflammation and caspase-3 as
      a proapotic marker were remarkably elevated in the intoxicated group of rats.
      Moreover, brain phospholipid profile was impaired in PPA-treated young rats
      recording lower levels of phosphatidylethanolamine (PE), phosphatidylserine (PS)
      and phosphatidylcholine (PC). CONCLUSIONS: Omega-3 fatty acids showed a
      protective effects on PPA - induced changes in rats as there was a remarkable
      amelioration of most of the measured parameters (i.e. higher GABA, 5HT, DA, PE,
      PS and PC) and lower Il-6, TNF-alpha and caspase-3.

PMID- 21854592
TI  - The tammar wallaby major histocompatibility complex shows evidence of past
      genomic instability.
AB  - BACKGROUND: The major histocompatibility complex (MHC) is a group of genes with a
      variety of roles in the innate and adaptive immune responses. MHC genes form a
      genetically linked cluster in eutherian mammals, an organization that is thought
      to confer functional and evolutionary advantages to the immune system. The tammar
      wallaby (Macropus eugenii), an Australian marsupial, provides a unique model for
      understanding MHC gene evolution, as many of its antigen presenting genes are not
      linked to the MHC, but are scattered around the genome. RESULTS: Here we describe
      the 'core' tammar wallaby MHC region on chromosome 2q by ordering and sequencing
      33 BAC clones, covering over 4.5 MB and containing 129 genes. When compared to
      the MHC region of the South American opossum, eutherian mammals and non-mammals,
      the wallaby MHC has a novel gene organization. The wallaby has undergone an
      expansion of MHC class II genes, which are separated into two clusters by the
      class III genes. The antigen processing genes have undergone duplication,
      resulting in two copies of TAP1 and three copies of TAP2. Notably, Kangaroo
      Endogenous Retroviral Elements are present within the region and may have
      contributed to the genomic instability. CONCLUSIONS: The wallaby MHC has been
      extensively remodeled since the American and Australian marsupials last shared a
      common ancestor. The instability is characterized by the movement of antigen
      presenting genes away from the core MHC, most likely via the presence and
      activity of retroviral elements. We propose that the movement of class II genes
      away from the ancestral class II region has allowed this gene family to expand
      and diversify in the wallaby. The duplication of TAP genes in the wallaby MHC
      makes this species a unique model organism for studying the relationship between
      MHC gene organization and function.

PMID- 21854593
TI  - Extended antimicrobial treatment of bacterial vaginosis combined with human
      lactobacilli to find the best treatment and minimize the risk of relapses.
AB  - BACKGROUND: The primary objective of this study was to investigate if extended
      antibiotic treatment against bacterial vaginosis (BV) together with adjuvant
      lactobacilli treatment could cure BV and, furthermore, to investigate factors
      that could cause relapse. METHODS: In all, 63 consecutive women with bacterial
      vaginosis diagnosed by Amsel criteria were offered a much more aggressive
      treatment of BV than used in normal clinical practice with repeated antibiotic
      treatment with clindamycin and metronidazole together with vaginal gelatine
      capsules containing different strains of lactobacilli both newly characterised
      and a commercial one (109 freeze-dried bacteria per capsule). Oral clindamycin
      treatment was also given to the patient's sexual partner. RESULTS: The cure rate
      was 74.6% after 6 months. The patients were then followed as long as possible or
      until a relapse. The cure rate was 65.1% at 12 months and 55.6% after 24 months.
      There was no significant difference in cure rate depending on which Lactobacillus
      strains were given to the women or if the women were colonised by lactobacilli.
      The most striking factor was a new sex partner during the follow up period where
      the Odds Ratio of having a relapse was 9.3 (2.8-31.2) if the patients had a new
      sex partner during the observation period. CONCLUSIONS: The study shows that
      aggressive treatment of the patient with antibiotics combined with specific
      Lactobacillus strain administration and partner treatment can provide long
      lasting cure. A striking result of our study is that change of partner is
      strongly associated with relapse of BV. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01245322.

PMID- 21854595
TI  - In Mycoplasma hominis the OppA-mediated cytoadhesion depends on its ATPase
      activity.
AB  - BACKGROUND: In Mycoplasma hominis, a facultative human pathogen of the human
      genital tract, OppA, the substrate-binding domain of the oligopeptide permease,
      is a multifunctional protein involved in nutrition uptake, cytoadhesion and
      hydrolysis of extracellular ATP. RESULTS: To map the function-related protein
      regions the ATPase activity and adhesive behavior of OppA mutants were analyzed.
      Mutations of the Walker BA motifs resulted in an inhibition of up to 8% of the
      OppA ATPase activity, whereas deletion of the N-terminal CS1 or the CS2 region,
      structural motifs that are conserved in bacterial OppA proteins, reduced ATPase
      activity to 60% and deletion of CS3, the third conserved region adjacent to the
      Walker B motif led to a reduction to 42% ATPase activity. Interestingly, adhesion
      of the OppA mutants to immobilized HeLa cells demonstrated that two distal
      regions are mainly involved in adherence of OppA: the CS1 region, deletion of
      which led to 35% of the cytoadhesion, and the Walker BA with the adjacent
      upstream region CS3, deletion of which led to 25% of the cytoadhesion. The
      influence of the ATPase activity on the adherence of M. hominis to HeLa cells was
      confirmed by the use of ATPase inhibitors which reduced mycoplasmal cytoadhesion
      to 50%. CONCLUSIONS: These findings suggest that the OppA-mediated cytoadherence
      of Mycoplasma hominis depends on both, the topology of the neighbouring CS1 and
      ATPase domain regions and the functionality of the ecto-ATPase activity in
      addition.

PMID- 21854596
TI  - Promoting smoking cessation in Pakistani and Bangladeshi men in the UK: pilot
      cluster randomised controlled trial of trained community outreach workers.
AB  - BACKGROUND: Smoking prevalence is high among Pakistani and Bangladeshi men in the
      UK, but there are few tailored smoking cessation programmes for Pakistani and
      Bangladeshi communities. The aim of this study was to pilot a cluster randomised
      controlled trial comparing the effectiveness of Pakistani and Bangladeshi smoking
      cessation outreach workers with standard care to improve access to and the
      success of English smoking cessation services. METHODS: A pilot cluster
      randomised controlled trial was conducted in Birmingham, UK. Geographical lower
      layer super output areas were used to identify natural communities where more
      than 10% of the population were of Pakistani and Bangladeshi origin. 16
      agglomerations of super output areas were randomised to normal care controls vs.
      outreach intervention. The number of people setting quit dates using NHS
      services, validated abstinence from smoking at four weeks, and stated abstinence
      at three and six months were assessed. The impact of the intervention on choice
      and adherence to treatments, attendance at clinic appointments and patient
      satisfaction were also assessed. RESULTS: We were able to randomise geographical
      areas and deliver the outreach worker-based services. More Pakistani and
      Bangladeshi men made quit attempts with NHS services in intervention areas
      compared with control areas, rate ratio (RR) 1.32 (95%CI: 1.03-1.69). There was a
      small increase in the number of 4-week abstinent smokers in intervention areas
      (RR 1.30, 95%CI: 0.82-2.06). The proportion of service users attending weekly
      appointments was lower in intervention areas than control areas. No difference
      was found between intervention and control areas in choice and adherence to
      treatments or patient satisfaction with the service. The total cost of the
      intervention was L124,000; an estimated cost per quality-adjusted life year
      (QALY) gained of L8,500. CONCLUSIONS: The intervention proved feasible and
      acceptable. Outreach workers expanded reach of smoking cessation services in
      diverse locations of relevance to Pakistani and Bangladeshi communities. The
      outreach worker model has the potential to increase community cessation rates and
      could prove cost-effective, but needs evaluating definitively in a larger,
      appropriately powered, randomised controlled trial. These future trials of
      outreach interventions need to be of sufficient duration to allow embedding of
      new models of service delivery. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN82127540.

PMID- 21854594
TI  - Transcriptomic analysis supports similar functional roles for the two thymuses of
      the tammar wallaby.
AB  - BACKGROUND: The thymus plays a critical role in the development and maturation of
      T-cells. Humans have a single thoracic thymus and presence of a second thymus is
      considered an anomaly. However, many vertebrates have multiple thymuses. The
      tammar wallaby has two thymuses: a thoracic thymus (typically found in all
      mammals) and a dominant cervical thymus. Researchers have known about the
      presence of the two wallaby thymuses since the 1800s, but no genome-wide research
      has been carried out into possible functional differences between the two thymic
      tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical
      and thoracic thymus from a single 178 day old tammar wallaby. RESULTS: We show
      that both the tammar thoracic and the cervical thymuses displayed gene expression
      profiles consistent with roles in T-cell development. Both thymuses expressed
      genes that mediate distinct phases of T-cells differentiation, including the
      initial commitment of blood stem cells to the T-lineage, the generation of T-cell
      receptor diversity and development of thymic epithelial cells. Crucial immune
      genes, such as chemokines were also present. Comparable patterns of expression of
      non-coding RNAs were seen. 67 genes differentially expressed between the two
      thymuses were detected, and the possible significance of these results are
      discussed. CONCLUSION: This is the first study comparing the transcriptomes of
      two thymuses from a single individual. Our finding supports that both thymuses
      are functionally equivalent and drive T-cell development. These results are an
      important first step in the understanding of the genetic processes that govern
      marsupial immunity, and also allow us to begin to trace the evolution of the
      mammalian immune system.

PMID- 21854597
TI  - Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in
      patients with locally advanced rectal cancer receiving neoadjuvant
      chemoradiotherapy.
AB  - BACKGROUND: For patients with locally advanced rectal cancer (LARC) neoadjuvant
      chemoradiotherapy is recommended as standard therapy. So far, no predictive or
      prognostic molecular factors for patients undergoing multimodal treatment are
      established. Increased angiogenesis and altered tumour metabolism as adaption to
      hypoxic conditions in cancers play an important role in tumour progression and
      metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor
      (VEGF-R) and Transketolase-like-1 (TKTL1) are related to hypoxic conditions in
      tumours. In search for potential prognostic molecular markers we investigated the
      expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with
      neoadjuvant chemoradiotherapy and cetuximab. METHODS: Tumour and corresponding
      normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median
      age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant
      chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with
      radiotherapy) were analysed by quantitative PCR. RESULTS: Significantly higher
      expression of VEGFR-1/2 was found in tumour tissue in pre-treatment biopsies as
      well as in resected specimen after neoadjuvant chemoradiotherapy compared to
      corresponding normal tissue. High TKTL1 expression significantly correlated with
      disease free survival. None of the markers had influence on early response
      parameters such as tumour regression grading. There was no correlation of gene
      expression between the investigated markers. CONCLUSION: High TKTL-1 expression
      correlates with poor prognosis in terms of 3 year disease-free survival in
      patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may
      therefore serve as a molecular prognostic marker which should be further
      evaluated in randomised clinical trials.

PMID- 21854598
TI  - Neighborhood built environment and physical activity of Japanese older adults:
      results from the Aichi Gerontological Evaluation Study (AGES).
AB  - BACKGROUND: Although many studies have reported the association between
      neighborhood built environment (BE) and physical activity (PA), less is known
      about the associations for older populations or in countries besides the US and
      Australia. The aim of this paper is to examine the associations for older adult
      populations in Japan. METHODS: Our analyses were based on cross-sectional data
      from the Aichi Gerontological Evaluation Study (AGES), conducted in 2003. The
      respondents were older adults, aged 65 years or over (n = 9,414), from 8
      municipalities across urban, suburban, and rural areas. The frequency of leisure
      time sports activity and total walking time were used as the outcome variables.
      Using geographic information systems (GIS), we measured residential density,
      street connectivity, number of local destinations, access to recreational spaces,
      and land slope of the respondents' neighborhoods, based on network distances with
      multiple radii (250 m, 500 m, 1,000 m). An ordinal logistic regression model was
      used to analyze the association between PA and BE measures. RESULTS: Population
      density and presence of parks or green spaces had positive associations with the
      frequency of sports activity, regardless of the selected buffer zone. The
      analysis of total walking time, however, showed only a few associations.
      CONCLUSIONS: Our findings provide mixed support for the association between PA
      and the characteristics of BE measures, previously used in Western settings. Some
      characteristics of the neighborhood built environment may facilitate leisure time
      sports activity, but not increase the total walking time for Japanese older
      adults.

PMID- 21854599
TI  - Self-esteem is associated with premorbid adjustment and positive psychotic
      symptoms in early psychosis.
AB  - BACKGROUND: Low levels of self-esteem have been implicated as both a cause and a
      consequence of severe mental disorders. The main aims of the study were to
      examine whether premorbid adjustment has an impact on the subject's self-esteem,
      and whether lowered self-esteem contributes to the development of delusions and
      hallucinations. METHOD: A total of 113 patients from the Thematically Organized
      Psychosis research study (TOP) were included at first treatment. The Positive and
      Negative Syndrome Scale (PANSS) was used to assess present symptoms. Premorbid
      adjustment was measured with the Premorbid Adjustment Scale (PAS) and self-esteem
      by the Rosenberg Self-Esteem Scale (RSES). RESULTS: Premorbid social adjustment
      was significantly related to lower self-esteem and explained a significant
      proportion of the variance in self-esteem. Self-esteem was significantly
      associated with the levels of persecutory delusions and hallucinations
      experienced by the patient and explained a significant proportion of the variance
      even after adjusting for premorbid functioning and depression. CONCLUSION: There
      are reasons to suspect that premorbid functioning is an important aspect in the
      development of self- esteem, and, furthermore, that self-esteem is associated
      with the development of delusions and hallucinations.

PMID- 21854600
TI  - Placental expression of pituitary hormones is an ancestral feature of therian
      mammals.
AB  - BACKGROUND: The placenta is essential for supplying nutrients and gases to the
      developing mammalian young before birth. While all mammals have a functional
      placenta, only in therian mammals (marsupials and eutherians) does the placenta
      closely appose or invade the uterine endometrium. The eutherian placenta secretes
      hormones that are structurally and functionally similar to pituitary growth
      hormone (GH), prolactin (PRL) and luteinizing hormone (LH). Marsupial and
      eutherian mammals diverged from a common ancestor approximately 125 to 148
      million years ago and developed distinct reproductive strategies. As in
      eutherians, marsupials rely on a short-lived but functional placenta for
      embryogenesis. RESULTS: We characterized pituitary GH, GH-R, IGF-2, PRL and
      LHbeta in a macropodid marsupial, the tammar wallaby, Macropus eugenii. These
      genes were expressed in the tammar placenta during the last third of gestation
      when most fetal growth occurs and active organogenesis is initiated. The mRNA of
      key growth genes GH, GH-R, IGF-2 and PRL were expressed during late pregnancy. We
      found significant up-regulation of GH, GH-R and IGF-2 after the start of the
      rapid growth phase of organogenesis which suggests that the placental growth
      hormones regulate the rapid phase of fetal growth. CONCLUSIONS: This is the first
      demonstration of the existence of pituitary hormones in the marsupial placenta.
      Placental expression of these pituitary hormones has clearly been conserved in
      marsupials as in eutherian mammals, suggesting an ancestral origin of the
      evolution of placental expression and a critical function of these hormones in
      growth and development of all therian mammals.

PMID- 21854601
TI  - Familial tumoral calcinosis in two Chinese patients: a case series.
AB  - INTRODUCTION: Tumoral calcinosis is a rare and benign condition characterized by
      massive subcutaneous soft tissue deposits of calcium phosphate predominantly
      around large joints. CASE PRESENTATION: Familial tumoral calcinosis was present
      in two members of a Han Chinese family, namely, the son and daughter. The 14-year
      old son had the first operation on his right sole of the foot at the age of six,
      and then experienced subsequent surgeries at a lesion in his right sole of the
      foot and left hip, respectively. The 16-year-old daughter underwent her first
      operation at the age of six in her left gluteal region, and subsequent surgeries
      were performed due to recurrence at the same lesion. Pathologic diagnoses of
      surgical specimens in both of the patients were reported as tumoral calcinosis.
      The laboratory results showed hyperphosphatemia with normal levels of serum
      calcium and alkaline phosphatase. Only surgical treatment was performed in both
      patients with satisfactory prognosis. CONCLUSION: This is the first report of
      Chinese familial tumoral calcinosis. The etiopathogenisis and treatment are
      discussed.

PMID- 21854602
TI  - Simulation of epiretinal prostheses - evaluation of geometrical factors affecting
      stimulation thresholds.
AB  - BACKGROUND: An accurate understanding of the electrical interaction between
      retinal prostheses and retinal tissue is important to design effective devices.
      Previous studies have used modelling approaches to simulate electric fields
      generated by epiretinal prostheses in saline and to simulate retinal ganglion
      cell (RGC) activation using passive or/and active biophysical models of the
      retina. These models have limited scope for studying an implanted human retinal
      prosthesis as they often do not account for real geometry and composition of the
      prosthesis-retina interface. This interface consists of real dimensions and
      location of stimulation and ground electrodes that are separated by the retinal
      tissue and surrounded by physiological fluids. METHODS: In this study, we
      combined the prosthesis-retina interface elements into a framework to evaluate
      the geometrical factors affecting stimulation thresholds for epiretinal
      prostheses used in clinical human trials, as described by Balthasar et al. in
      their Investigative Ophthalmology and Visual Science (IOVS) paper published in
      2008 using the Argus I epiretinal implants. Finite element method (FEM) based
      computations were used to estimate threshold currents based on a threshold
      criterion employing a passive electric model of the retina. RESULTS: Threshold
      currents and impedances were estimated for different electrode-retina distances.
      The profiles and the values for thresholds and impedances obtained from our
      simulation framework are within the range of measured values in the only
      elaborate published clinical trial until now using Argus I epiretinal implants.
      An estimation of resolution for the electrodes used in these trials was provided.
      Our results reiterate the importance of close proximity between electrodes and
      retina for safe and efficient retinal stimulation. CONCLUSIONS: The validation of
      our simulation framework being relevant for epiretinal prosthesis research is
      derived from the good agreement of the computed trends and values of the current
      study with measurements demonstrated in existing clinical trials on humans (Argus
      I). The proposed simulation framework could be used to generate the relationship
      between threshold and impedance for any electrode geometry and consequently be an
      effective tool for design engineers, surgeons and electrophysiologists.

PMID- 21854603
TI  - Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma
      homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of
      Brazil.
AB  - BACKGROUND/AIM: Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase
      (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently
      associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in
      a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from
      Northeast of Brazil. METHOD: One hundred seven-four untreated patients with CHC
      were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral
      blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The
      homocysteine (Hcy) levels were determined by chemiluminescence method. All
      patients were negative for markers of Wilson's disease, hemochromatosis and
      autoimmune diseases and have current and past daily alcohol intake less than 100
      g/week. RESULTS: Among subjects infected with CHC genotype non-1 the frequency of
      MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless,
      association was found between the MTHFR genotype TT * CT/CC polymorphism and the
      degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A
      significant difference was found on plasma Hcy levels in patients with steatosis
      regardless of HCV genotype (p = 0.03). CONCLUSION: Our results indicate that
      plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with
      steatosis regardless of HCV genotype and vitamin deficiency. The presence of
      genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1
      infected patient regardless of histopathological classification and genotype
      TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of
      steatosis in CHC infected patients from the northeast of Brazil regardless of HCV
      genotype. The genetic susceptibility of MTHFR C677T polymorphism should be
      confirmed in a large population.

PMID- 21854604
TI  - Downregulation of CREB expression in Alzheimer's brain and in Abeta-treated rat
      hippocampal neurons.
AB  - BACKGROUND: Oxidative stress plays an important role in neuronal dysfunction and
      neuron loss in Alzheimer's brain. Previous studies have reported downregulation
      of CREB-mediated transcription by oxidative stress and Abeta. The promoter for
      CREB itself contains cyclic AMP response elements. Therefore, we examined the
      expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem
      brain and in cultured rat hippocampal neurons exposed to Abeta aggregates.
      RESULTS: Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse
      brain revealed decreases in the mRNA levels of CREB and its target, BDNF.
      Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB
      levels in hippocampus and cortex. Markers of oxidative stress were detected in
      transgenic mouse brain and decreased CREB staining was observed in regions
      showing abundance of astrocytes. There was also an inverse correlation between
      SDS-extracted Abeta and CREB protein levels in Alzheimer's post-mortem
      hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase
      inhibitor, decreased and the active cleaved form of caspase-9, a marker for the
      intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat
      primary hippocampal neurons to Abeta fibrils decreased CREB promoter activity.
      Decrease in CREB mRNA levels in Abeta-treated neurons was reversed by the
      antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction
      led to significant protection against Abeta-induced neuronal apoptosis.
      CONCLUSIONS: Our findings suggest that chronic downregulation of CREB-mediated
      transcription results in decrease of CREB content in the hippocampal neurons of
      AD brain which may contribute to exacerbation of disease progression.

PMID- 21854605
TI  - G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir
      whereas Y143C does not.
AB  - BACKGROUND: HIV-2 is endemic in West Africa and has spread throughout Europe.
      However, the alternatives for HIV-2-infected patients are more limited than for
      HIV-1. Raltegravir, an integrase inhibitor, is active against wild-type HIV-2,
      with a susceptibility to this drug similar to that of HIV-1, and is therefore a
      promising option for use in the treatment of HIV-2-infected patients. Recent
      studies have shown that HIV-2 resistance to raltegravir involves one of three
      resistance mutations, N155H, Q148R/H and Y143C, previously identified as
      resistance determinants in the HIV-1 integrase coding sequence. The resistance of
      HIV-1 IN has been confirmed in vitro for mutated enzymes harboring these
      mutations, but no such confirmation has yet been obtained for HIV-2. RESULTS: The
      integrase coding sequence was amplified from plasma samples collected from ten
      patients infected with HIV-2 viruses, of whom three RAL-naive and seven on RAL
      based treatment at the time of virological failure. The genomes of the resistant
      strains were cloned and three patterns involving N155H, G140S/Q148R or Y143C
      mutations were identified. Study of the susceptibility of integrases, either
      amplified from clinical isolates or obtained by mutagenesis demonstrated that
      mutations at positions 155 and 148 render the integrase resistant to RAL. The
      G140S mutation conferred little resistance, but compensated for the catalytic
      defect due to the Q148R mutation. Conversely, Y143C alone did not confer
      resistance to RAL unless E92Q is also present. Furthermore, the introduction of
      the Y143C mutation into the N155H resistant background decreased the resistance
      level of enzymes containing the N155H mutation. CONCLUSION: This study confirms
      that HIV-2 resistance to RAL is due to the N155H, G140S/Q148R or E92Q/Y143C
      mutations. The N155H and G140S/Q148R mutations make similar contributions to
      resistance in both HIV-1 and HIV-2, but Y143C is not sufficient to account for
      the resistance of HIV-2 genomes harboring this mutation. For Y143C to confer
      resistance in vitro, it must be accompanied by E92Q, which therefore plays a more
      important role in the HIV-2 context than in the HIV-1 context. Finally, the Y143C
      mutation counteracts the resistance conferred by the N155H mutation, probably
      accounting for the lack of detection of these mutations together in a single
      genome.

PMID- 21854606
TI  - Modeling factors influencing the demand for emergency department services in
      Ontario: a comparison of methods.
AB  - BACKGROUND: Emergency departments are medical treatment facilities, designed to
      provide episodic care to patients suffering from acute injuries and illnesses as
      well as patients who are experiencing sporadic flare-ups of underlying chronic
      medical conditions which require immediate attention. Supply and demand for
      emergency department services varies across geographic regions and time. Some
      persons do not rely on the service at all whereas; others use the service on
      repeated occasions. Issues regarding increased wait times for services and
      crowding illustrate the need to investigate which factors are associated with
      increased frequency of emergency department utilization. The evidence from this
      study can help inform policy makers on the appropriate mix of supply and demand
      targeted health care policies necessary to ensure that patients receive
      appropriate health care delivery in an efficient and cost-effective manner. The
      purpose of this report is to assess those factors resulting in increased demand
      for emergency department services in Ontario. We assess how utilization rates
      vary according to the severity of patient presentation in the emergency
      department. We are specifically interested in the impact that access to primary
      care physicians has on the demand for emergency department services.
      Additionally, we wish to investigate these trends using a series of novel
      regression models for count outcomes which have yet to be employed in the domain
      of emergency medical research. METHODS: Data regarding the frequency of emergency
      department visits for the respondents of Canadian Community Health Survey (CCHS)
      during our study interval (2003-2005) are obtained from the National Ambulatory
      Care Reporting System (NACRS). Patients' emergency department utilizations were
      linked with information from the Canadian Community Health Survey (CCHS) which
      provides individual level medical, socio-demographic, psychological and
      behavioral information for investigating predictors of increased emergency
      department utilization. Six different multiple regression models for count data
      were fitted to assess the influence of predictors on demand for emergency
      department services, including: Poisson, Negative Binomial, Zero-Inflated
      Poisson, Zero-Inflated Negative Binomial, Hurdle Poisson, and Hurdle Negative
      Binomial. Comparison of competing models was assessed by the Vuong test
      statistic. RESULTS: The CCHS cycle 2.1 respondents were a roughly equal mix of
      males (50.4%) and females (49.6%). The majority (86.2%) were young-middle aged
      adults between the ages of 20-64, living in predominantly urban environments
      (85.9%), with mid-high household incomes (92.2%) and well-educated, receiving at
      least a high-school diploma (84.1%). Many participants reported no chronic
      disease (51.9%), fell into a small number (0-5) of ambulatory diagnostic groups
      (62.3%), and perceived their health status as good/excellent (88.1%); however,
      were projected to have high Resource Utilization Band levels of health resource
      utilization (68.2%). These factors were largely stable for CCHS cycle 3.1
      respondents. Factors influencing demand for emergency department services varied
      according to the severity of triage scores at initial presentation. For example,
      although a non-significant predictor of the odds of emergency department
      utilization in high severity cases, access to a primary care physician was a
      statistically significant predictor of the likelihood of emergency department
      utilization (OR: 0.69; 95% CI OR: 0.63-0.75) and the rate of emergency department
      utilization (RR: 0.57; 95% CI RR: 0.50-0.66) in low severity cases. CONCLUSION:
      Using a theoretically appropriate hurdle negative binomial regression model this
      unique study illustrates that access to a primary care physician is an important
      predictor of both the odds and rate of emergency department utilization in
      Ontario. Restructuring primary care services, with aims of increasing access to
      undersupplied populations may result in decreased emergency department
      utilization rates by approximately 43% for low severity triage level cases.

PMID- 21854607
TI  - Single-cell copy number variation detection.
AB  - Detection of chromosomal aberrations from a single cell by array comparative
      genomic hybridization (single-cell array CGH), instead of from a population of
      cells, is an emerging technique. However, such detection is challenging because
      of the genome artifacts and the DNA amplification process inherent to the single
      cell approach. Current normalization algorithms result in inaccurate aberration
      detection for single-cell data. We propose a normalization method based on
      channel, genome composition and recurrent genome artifact corrections. We
      demonstrate that the proposed channel clone normalization significantly improves
      the copy number variation detection in both simulated and real single-cell array
      CGH data.

PMID- 21854608
TI  - High catechin concentrations detected in Withania somnifera (ashwagandha) by high
      performance liquid chromatography analysis.
AB  - BACKGROUND: Withania somnifera is an important medicinal plant traditionally used
      in the treatment of many diseases. The present study was carried out to
      characterize the phenolic acids, flavonoids and 1,1-diphenyl-2-picrylhydrazyl
      radical (DPPH) scavenging activities in methanolic extracts of W. somnifera
      fruits, roots and leaves (WSFEt, WSREt and WSLEt). METHODS: WSFEt, WSREt and
      WSLEt was prepared by using 80% aqueous methanol and total polyphenols,
      flavonoids as well as DPPH radical scavenging activities were determined by
      spectrophotometric methods and phenolic acid profiles were determined by HPLC
      methods. RESULTS: High concentrations of both phenolics and flavonoids were
      detected in all parts of the plant with the former ranging between 17.80 +/- 5.80
      and 32.58 +/- 3.16 mg/g (dry weight) and the latter ranging between 15.49 +/-
      1.02 and 31.58 +/- 5.07 mg/g. All of the three different plant parts showed
      strong DPPH radical scavenging activities (59.16 +/- 1.20 to 91.84 +/- 0.38%).
      Eight polyphenols (gallic, syringic, benzoic, p-coumaric and vanillic acids as
      well as catechin, kaempferol and naringenin) have been identified by HPLC in
      parts of the plant as well. Among all the polyphenols, catechin was detected in
      the highest concentration (13.01 +/- 8.93 to 30.61 +/- 11.41 mg/g). CONCLUSION:
      The results indicating that W. somnifera is a plant with strong therapeutic
      properties thus further supporting its traditional claims. All major parts of W.
      somnifera such as the roots, fruits and leaves provide potential benefits for
      human health because of its high content of polyphenols and antioxidant
      activities with the leaves containing the highest amounts of polyphenols
      specially catechin with strong antioxidant properties.

PMID- 21854610
TI  - Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter
      clustering in the MetS.
AB  - BACKGROUND: Previous analysis clustered 1,238 individuals from the general
      population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of
      their fasting very low-density, low-density and high-density lipoproteins (VLDL,
      LDL, HDL) using latent class analysis. From two of the eight identified groups (N
      = 251), ~75% of individuals met Adult Treatment Panel III criteria for the
      metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm);
      however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group
      2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed
      significantly more insulin resistance (IR), and accompanying higher waist
      circumference and fasting glucose and triglycerides (all P < .01). Since
      lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined
      whether these two patterns of lipoprotein diameter were associated with
      differences across two lipoprotein lipase (LPL) gene variants: D9N (rs1801177)
      and S447X (rs328). FINDINGS: Mixed linear models that controlled for age, sex,
      center of data collection, and family pedigree revealed no differences between
      the two groups for the D9N polymorphism (P = .36). However, group 2 contained
      significantly more carriers (25%) of the 447X variant than group 1 (14%; P =
      .04). CONCLUSIONS: This was the first study this kind to show an association
      between LPL and large VLDL particle size within the MetS, a pattern associated
      with higher IR. Future work should extend this to larger samples to confirm these
      findings, and examine the long term outcomes of those with this lipoprotein
      diameter pattern.

PMID- 21854609
TI  - A school-based intervention to promote physical activity among adolescent girls:
      rationale, design, and baseline data from the Girls in Sport group randomised
      controlled trial.
AB  - BACKGROUND: Physical activity levels decline markedly among girls during
      adolescence. School-based interventions that are multi-component in nature,
      simultaneously targeting curricular, school environment and policy, and community
      links, are a promising approach for promoting physical activity. This report
      describes the rationale, design and baseline data from the Girls in Sport group
      randomised trial, which aims to prevent the decline in moderate-to-vigorous
      intensity physical activity (MVPA) among adolescent girls. METHODS/DESIGN: A
      community-based participatory research approach and action learning framework are
      used with measurements at baseline and 18-month follow-up. Within each
      intervention school, a committee develops an action plan aimed at meeting the
      primary objective (preventing the decline in accelerometer-derived MVPA).
      Academic partners and the State Department of Education and Training act as
      critical friends. Control schools continue with their usual school programming.
      24 schools were matched then randomized into intervention (n = 12) and control (n
      = 12) groups. A total of 1518 girls (771 intervention and 747 control) completed
      baseline assessments (86% response rate). Useable accelerometer data (>= 10
      hrs/day on at least 3 days) were obtained from 79% of this sample (n = 1199).
      Randomisation resulted in no differences between intervention and control groups
      on any of the outcomes. The mean age (SE) of the sample was 13.6 (+/- 0.02) years
      and they spent less than 5% of their waking hours in MVPA (4.85 +/- 0.06).
      DISCUSSION: Girls in Sport will test the effectiveness of schools working towards
      the same goal, but developing individual, targeted interventions that bring about
      changes in curriculum, school environment and policy, and community links. By
      using community-based participatory research and an action learning framework in
      a secondary school setting, it aims to add to the body of literature on effective
      school-based interventions through promoting and sustaining increased physical
      activity participation among adolescent girls. TRIAL REGISTRATION NUMBER:
      Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610001077055.

PMID- 21854611
TI  - Health risk factors and self-rated health among job-seekers.
AB  - BACKGROUND: To determine a) proportions of behavior related health risk factors
      among job-seekers and b) to what extend these are related to self-rated health.
      METHODS: Over 12 months, job-seekers were recruited at three job-agencies in
      northeastern Germany. Among all individuals eligible for study inclusion, 7,906
      (79.8%) provided information on smoking, risky drinking, overweight/obesity (body
      mass index), fruit and vegetable intake, physical inactivity, illicit drug use,
      and self-rated health. Proportions and 95% confidence intervals stratified by
      gender, age and duration of unemployment were calculated. Multivariate logistic
      regression analyses predicting self-rated health were conducted. RESULTS: The
      proportions of each health-risk factor were high, and 52.4% of the sample (53.4%
      male, 33.5 years mean age) had 3 or more health risk factors. Mostly, the
      proportions were particularly high among men and long-term unemployed
      individuals; e.g. 84.8% of the 18-24 year old long-term unemployed men were
      current smokers. Proportions of substance use related health risk factors were
      highest among the 18-24 year olds (e.g. risky drinking 28.7%), and proportions of
      health risk factors related to nutrition and physical inactivity were highest
      among the 40-64 year olds (e.g. overweight/obesity 65.4%). Depending on gender,
      all health risk factors and having 3 or more health risk factors were associated
      with lower self-rated health; odd ratios ranged between 1.2 for smoking (95% CI:
      1.0-1.3) and 1.7 for overweight and physical inactivity (95% CI: 1.5-1.9).
      CONCLUSIONS: Prevention efforts to reduce health risk factors and to increase
      health among job-seekers are needed, and job agencies appear a feasible setting
      for their implementation.

PMID- 21854613
TI  - Determining factors of thermoelectric properties of semiconductor nanowires.
AB  - It is widely accepted that low dimensionality of semiconductor heterostructures
      and nanostructures can significantly improve their thermoelectric efficiency.
      However, what is less well understood is the precise role of electronic and
      lattice transport coefficients in the improvement. We differentiate and analyze
      the electronic and lattice contributions to the enhancement by using a nearly
      parameter-free theory of the thermoelectric properties of semiconductor
      nanowires. By combining molecular dynamics, density functional theory, and
      Boltzmann transport theory methods, we provide a complete picture for the
      competing factors of thermoelectric figure of merit. As an example, we study the
      thermoelectric properties of ZnO and Si nanowires. We find that the figure of
      merit can be increased as much as 30 times in 8-A-diameter ZnO nanowires and 20
      times in 12-A-diameter Si nanowires, compared with the bulk. Decoupling of
      thermoelectric contributions reveals that the reduction of lattice thermal
      conductivity is the predominant factor in the improvement of thermoelectric
      properties in nanowires. While the lattice contribution to the efficiency
      enhancement consistently becomes larger with decreasing size of nanowires, the
      electronic contribution is relatively small in ZnO and disadvantageous in Si.

PMID- 21854612
TI  - Cellular viability effects of fatty acid amide hydrolase inhibition on cerebellar
      neurons.
AB  - The endocannabinoid anandamide (ANA) participates in the control of cell death
      inducing the formation of apoptotic bodies and DNA fragmentation. The aim of this
      study was to evaluate whether the ANA degrading enzyme, the fatty acid amide
      hydrolase (FAAH), would induce cellular death. Experiments were performed in
      cerebellar granule neurons cultured with the FAAH inhibitor, URB597 (25, 50 or
      100 nM) as well as endogenous lipids such as oleoylethanolamide (OEA) or
      palmitoylethanolamide (PEA) and cellular viability was determined by MTT test.
      Neurons cultured with URB597 (25, 50 or 100 nM) displayed a decrease in cellular
      viability. In addition, if cultured with OEA (25 nM) or PEA (100 nM), cellular
      death was found. These results further suggest that URB597, OEA or PEA promote
      cellular death.

PMID- 21854614
TI  - The Box-Cox power transformation on nursing sensitive indicators: does it matter
      if structural effects are omitted during the estimation of the transformation
      parameter?
AB  - BACKGROUND: Many nursing and health related research studies have continuous
      outcome measures that are inherently non-normal in distribution. The Box-Cox
      transformation provides a powerful tool for developing a parsimonious model for
      data representation and interpretation when the distribution of the dependent
      variable, or outcome measure, of interest deviates from the normal distribution.
      The objectives of this study was to contrast the effect of obtaining the Box-Cox
      power transformation parameter and subsequent analysis of variance with or
      without a priori knowledge of predictor variables under the classic linear or
      linear mixed model settings. METHODS: Simulation data from a 3 * 4 factorial
      treatments design, along with the Patient Falls and Patient Injury Falls from the
      National Database of Nursing Quality Indicators (NDNQI(r) for the 3rd quarter of
      2007 from a convenience sample of over one thousand US hospitals were analyzed.
      The effect of the nonlinear monotonic transformation was contrasted in two ways:
      a) estimating the transformation parameter along with factors with potential
      structural effects, and b) estimating the transformation parameter first and then
      conducting analysis of variance for the structural effect. RESULTS: Linear model
      ANOVA with Monte Carlo simulation and mixed models with correlated error terms
      with NDNQI examples showed no substantial differences on statistical tests for
      structural effects if the factors with structural effects were omitted during the
      estimation of the transformation parameter. CONCLUSIONS: The Box-Cox power
      transformation can still be an effective tool for validating statistical
      inferences with large observational, cross-sectional, and hierarchical or
      repeated measure studies under the linear or the mixed model settings without
      prior knowledge of all the factors with potential structural effects.

PMID- 21854615
TI  - Statistical methods for analyzing immunosignatures.
AB  - BACKGROUND: Immunosignaturing is a new peptide microarray based technology for
      profiling of humoral immune responses. Despite new challenges, immunosignaturing
      gives us the opportunity to explore new and fundamentally different research
      questions. In addition to classifying samples based on disease status, the
      complex patterns and latent factors underlying immunosignatures, which we attempt
      to model, may have a diverse range of applications. METHODS: We investigate the
      utility of a number of statistical methods to determine model performance and
      address challenges inherent in analyzing immunosignatures. Some of these methods
      include exploratory and confirmatory factor analyses, classical significance
      testing, structural equation and mixture modeling. RESULTS: We demonstrate an
      ability to classify samples based on disease status and show that
      immunosignaturing is a very promising technology for screening and presymptomatic
      screening of disease. In addition, we are able to model complex patterns and
      latent factors underlying immunosignatures. These latent factors may serve as
      biomarkers for disease and may play a key role in a bioinformatic method for
      antibody discovery. CONCLUSION: Based on this research, we lay out an analytic
      framework illustrating how immunosignatures may be useful as a general method for
      screening and presymptomatic screening of disease as well as antibody discovery.

PMID- 21854616
TI  - A second-generation anchored genetic linkage map of the tammar wallaby (Macropus
      eugenii).
AB  - BACKGROUND: The tammar wallaby, Macropus eugenii, a small kangaroo used for
      decades for studies of reproduction and metabolism, is the model Australian
      marsupial for genome sequencing and genetic investigations. The production of a
      more comprehensive cytogenetically-anchored genetic linkage map will
      significantly contribute to the deciphering of the tammar wallaby genome. It has
      great value as a resource to identify novel genes and for comparative studies,
      and is vital for the ongoing genome sequence assembly and gene ordering in this
      species. RESULTS: A second-generation anchored tammar wallaby genetic linkage map
      has been constructed based on a total of 148 loci. The linkage map contains the
      original 64 loci included in the first-generation map, plus an additional 84
      microsatellite loci that were chosen specifically to increase coverage and assist
      with the anchoring and orientation of linkage groups to chromosomes. These
      additional loci were derived from (a) sequenced BAC clones that had been
      previously mapped to tammar wallaby chromosomes by fluorescence in situ
      hybridization (FISH), (b) End sequence from BACs subsequently FISH-mapped to
      tammar wallaby chromosomes, and (c) tammar wallaby genes orthologous to opossum
      genes predicted to fill gaps in the tammar wallaby linkage map as well as three X
      linked markers from a published study. Based on these 148 loci, eight linkage
      groups were formed. These linkage groups were assigned (via FISH-mapped markers)
      to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4
      cM, which is estimated to provide 82.6% total coverage of the genome, with an
      average interval distance of 10.9 cM between adjacent markers. The overall ratio
      of female/male map length is 0.84, which is comparable to the ratio of 0.78
      obtained for the first-generation map. CONCLUSIONS: Construction of this second
      generation genetic linkage map is a significant step towards complete coverage of
      the tammar wallaby genome and considerably extends that of the first-generation
      map. It will be a valuable resource for ongoing tammar wallaby genetic research
      and assembling the genome sequence. The sex-pooled map is available online at
      http://compldb.angis.org.au/.

PMID- 21854617
TI  - Effectiveness of an online group course for adolescents and young adults with
      depressive symptoms: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Depression is a common condition whose first onset is usually in late
      adolescence or early adulthood. Internet-based interventions are an effective
      treatment approach to depression. The aim of this study is to investigate the
      effectiveness of a Dutch online cognitive-behavioural group course known as
      Master Your Mood (Grip op Je Dip) for young people reporting depressive symptoms.
      Secondary research questions involve maintenance of effect at 6 months,
      mediators, and predictors of better outcomes. METHODS: We will conduct a
      randomised controlled trial (RCT) in which 244 young people aged 16-25 are
      randomly allocated to the Grip op Je Dip (GOJD) online group course or to a
      waiting list control group. The participants will be recruited from the general
      population. The primary outcome measure will be the severity of depressive
      symptoms according to the Center for Epidemiological Studies Depression Scale
      (CES-D). Other outcomes will include anxiety (Hospital Anxiety and Depression
      Scale-Anxiety, HADS) and mastery (Mastery Scale). Assessments will take place in
      both groups at baseline and three months later. Effect maintenance will be
      studied in the GOJD group six months after baseline, with missing data imputed
      using the expectation-maximisation method. Mediators and predictors of better
      outcomes will also be identified. DISCUSSION: The trial should add to the body of
      knowledge on the effectiveness of Internet-based interventions for depression. To
      our knowledge, this will be the first RCT on an online group intervention in this
      field. TRIAL REGISTRATION: NTR1694.

PMID- 21854618
TI  - Knowledge of family health program practitioners in Brazil about sickle cell
      disease: a descriptive, cross-sectional study.
AB  - BACKGROUND: Although sickle cell disease is an important public health problem in
      Brazil, there is a gap in the literature on the level of knowledge of primary
      health care professionals about the treatment and management of sickle cell
      disease. Therefore, this study aimed to evaluate the level of knowledge about
      sickle cell disease of physicians and nurses who work in the Family Health
      Program in a region of Brazil with a high prevalence of this disease. METHODS:
      This is a descriptive, cross-sectional study conducted at the municipality of
      Montes Claros, in the north of Minas Gerais, Brazil. Study participants included
      96 physicians and nurses who work at the Family Health Program in an urban area
      of the city. Data was collected using an original, partially tested questionnaire
      based on health care check points for children with sickle cell disease
      established in educational protocols from the State Health Secretary of Minas
      Gerais and the Ministry of Health. The structured questionnaire contained 47
      questions addressing three axes: epidemiology (8 questions); clinical
      manifestations (13 questions); and management of children with sickle cell
      disease (26 questions). Knowledge was measured through mean correct responses to
      proposed questions. Ethical principles were respected and this project was
      approved by the Committee of Ethics in Research. RESULTS: 59.4% (57) of the study
      participants were nurses and 40.6% (39) were physicians. The median length of
      training and median length of service in primary health care were 4.3 (2.8-8.0)
      years and 4.0 (2.0-7.1) years, respectively. The mean performance in knowledge
      tests was < 75%, with 5.7/8 (SD = 1.4) for the "epidemiology" questions; 8.6/13
      (SD = 2.2) for "clinical manifestations"; and 17.0/26 (SD = 2.9) for "management
      of children with sickle cell disease" questions; resulting in a mean total of
      31.4/47 (SD = 5.10) correct responses. A statistically significant association
      was found between the number of correct responses and family health care
      qualifications (p = 0.015). CONCLUSION: There is an urgent need to improve
      primary health care professional training in the care of children with sickle
      cell disease.

PMID- 21854619
TI  - The effect of the histone deacetylase inhibitor M344 on BRCA1 expression in
      breast and ovarian cancer cells.
AB  - BACKGROUND: The inhibition of Breast Cancer 1 (BRCA1) expression sensitizes
      breast and ovarian cancer cells to platinum chemotherapy. However,
      therapeutically relevant agents that target BRCA1 expression have not been
      identified. Our recent report suggested the potential of the histone deacetylase
      (HDAC) inhibitor, M344, to inhibit BRCA1 expression. In this study, we further
      evaluated the effect of M344 on BRCA1 mRNA and protein expression, as well as its
      effect on cisplatin-induced cytotoxicity in various breast (MCF7, T-47D and
      HCC1937) and ovarian (A2780s, A2780cp and OVCAR-4) cancer cell lines. RESULTS:
      With the addition of M344, the platinum-sensitive breast and ovarian cancer cell
      lines that displayed relatively high BRCA1 protein levels demonstrated
      significant potentiation of cisplatin cytotoxicity in association with a
      reduction of BRCA1 protein. The cisplatin-resistant cell lines, T-47D and A2780s,
      elicited increased cytotoxicity of cisplatin with M344 and down regulation of
      BRCA1 protein levels. A2780s cells subjected to combination platinum and M344
      treatment, demonstrated increased DNA damage as assessed by the presence of
      phosphorylated H2A.X foci in comparison to either treatment alone. Using
      Chromatin Immunoprecipitation, A2780s and MCF7 cells exposed to M344 alone and in
      combination with cisplatin, did not demonstrate enhanced acetylated Histone 4 at
      the BRCA1 promoter, suggesting an indirect effect on this promoter. CONCLUSIONS:
      The enhanced sensitivity of HDAC inhibition to platinum may be mediated through a
      BRCA1-dependent mechanism in breast and ovarian cancer cells. The findings of
      this study may be important in the future design of clinical trials involving
      HDAC inhibitors using BRCA1 as a tumour biomarker.

PMID- 21854620
TI  - Back complaints in the elders (BACE); design of cohort studies in primary care:
      an international consortium.
AB  - BACKGROUND: Although back complaints are common among older people, limited
      information is available in the literature about the clinical course of back pain
      in older people and the identification of older persons at risk for the
      transition from acute back complaints to chronic back pain. The aim of this study
      is to assess the course of back complaints and identify prognostic factors for
      the transition from acute back complaints to chronic back complaints in older
      people who visit a primary health care physician. METHODS/DESIGN: The design is a
      prospective cohort study with one-year follow-up. There will be no interference
      with usual care. Patients older than 55 years who consult a primary health care
      physician with a new episode of back complaints will be included in this study.
      Data will be collected using a questionnaire, physical examination and X-ray at
      baseline, and follow-up questionnaires after 6 weeks and 3, 6, 9 and 12 months.
      The study 'Back Complaints in the Elders' (BACE) will take place in different
      countries: starting in the Netherlands, Brazil and Australia. The research groups
      collaborate in the BACE consortium. The design and basic objectives of the study
      will be the same across the studies. DISCUSSION: This consortium is a
      collaboration between different research groups, aiming to provide insight into
      the course of back complaints in older people and to identify prognostic factors
      for the transition from acute back complaints to chronic back complaints in older
      persons. The BACE consortium allows to investigate differences between older
      people with back complaints and the health care systems in the different
      countries and to increase the statistical power by enabling meta-analyses using
      the individual patient data. Additional research groups worldwide are invited to
      join the BACE consortium.

PMID- 21854621
TI  - High efficient isolation and systematic identification of human adipose-derived
      mesenchymal stem cells.
AB  - BACKGROUND: Developing efficient methods to isolate and identify human adipose
      derived mesenchymal stem cells (hADSCs) remains to be one of the major challenges
      in tissue engineering. METHODS: We demonstrate here a method by isolating hADSCs
      from abdominal subcutaneous adipose tissue harvested during caesarian section.
      The hADSCs were isolated from human adipose tissue by collagenase digestion and
      adherence to flasks. RESULTS: The yield reached around 1 * 10(6) hADSCs per gram
      adipose tissue. The following comprehensive identification and characterization
      illustrated pronounced features of mesenchymal stem cells (MSCs). The fibroblast
      like hADSCs exhibited typical ultrastructure details for vigorous cell
      activities. Karyotype mapping showed normal human chromosome. With unique
      immunophenotypes they were positive for CD29, CD44, CD73, CD105 and CD166, but
      negative for CD31, CD34, CD45 and HLA-DR. The growth curve and cell cycle
      analysis revealed high capability for self-renewal and proliferation. Moreover,
      these cells could be functionally induced into adipocytes, osteoblasts, and
      endothelial cells in the presence of appropriate conditioned media. CONCLUSION:
      The data presented here suggest that we have developed high efficient isolation
      and cultivation methods with a systematic strategy for identification and
      characterization of hADSCs. These techniques will be able to provide safe and
      stable seeding cells for research and clinical application.

PMID- 21854622
TI  - Physical activity and sedentary behaviours in Greek-Cypriot children and
      adolescents: a cross-sectional study.
AB  - BACKGROUND: There are no data on physical activity and sedentary behaviours of
      Greek-Cypriot children and adolescents, and no study to date examined the
      association between these two behaviours in this population. The purpose of this
      study was to document the prevalence of physical activity and sedentary
      behaviours among Greek-Cypriot adolescents and examine the association between
      physical activity and a range of sedentary behaviours. Logistic regression
      analyses were performed to examine the association between physical activity and
      sedentary behaviours. METHODS: A cross-sectional study among 1,966 Greek-Cypriot
      children and adolescents was conducted in 2008/2009. Data were collected by means
      of a questionnaire across primary, middle, high and technical/vocational schools.
      RESULTS: Overall 52.3% and 52.4% of the participants met physical activity and
      television viewing guidelines respectively. Boys and younger children were more
      likely to meet guidelines. Boys who attended sports clubs for two or more times
      per week were more likely to be physically active (OR = 3.4), and those who
      listened to music for one or less than one hour per day were less likely to be
      physically active (OR = 0.6). Girls who attended sports clubs for two or more
      times per week and who watched television for two or less than two hours per day
      were more likely to be physically active, (OR = 3.0 and OR = 1.5 respectively).
      Girls who reported travelling by car/bus/motorbike for one or less than one hour
      per day were more likely to actively travel to school (OR = 1.8). CONCLUSIONS:
      Findings from this study provide limited support for the displacement hypothesis
      whereby sedentary behaviours displace physically active time. About 50.0% of
      Greek children and adolescents in Cyprus meet existing physical activity and
      television viewing guidelines. Encouraging children to attend sports clubs for at
      least two times per week may markedly improve their physical activity levels.

PMID- 21854623
TI  - Testing the importance of jasmonate signalling in induction of plant defences
      upon cabbage aphid (Brevicoryne brassicae) attack.
AB  - BACKGROUND: Phloem-feeding aphids deprive plants of assimilates, but mostly
      manage to avoid causing the mechanical tissue damage inflicted by chewing
      insects. Nevertheless, jasmonate signalling that is induced by infestation is
      important in mediating resistance to phloem feeders. Aphid attack induces the
      jasmonic acid signalling pathway, but very little is known about the specific
      impact jasmonates have on the expression of genes that respond to aphid attack.
      RESULTS: We have evaluated the function that jasmonates have in regulating
      Arabidopsis thaliana responses to cabbage aphid (Brevicoryne brassicae) by
      conducting a large-scale transcriptional analysis of two mutants: aos, which is
      defective in jasmonate production, and fou2, which constitutively induces
      jasmonic acid biosynthesis. This analysis enabled us to determine which genes'
      expression patterns depend on the jasmonic acid signalling pathway. We identified
      more than 200 genes whose expression in non-challenged plants depended on
      jasmonate levels and more than 800 genes that responded differently to
      infestation in aos and fou2 plants than in wt. Several aphid-induced changes were
      compromised in the aos mutant, particularly genes connected to regulation of
      transcription, defence responses and redox changes. Due to jasmonate-triggered
      pre-activation of fou2, its transcriptional profile in non-challenged plants
      mimicked the induction of defence responses in wt. Additional activation of fou2
      upon aphid attack was therefore limited. Insect fitness experiments revealed that
      the physiological consequences of fou2 mutation contributed to more effective
      protection against B. brassicae. However, the observed resistance of the fou2
      mutant was based on antibiotic rather than feeding deterrent properties of the
      mutant as indicated by an analysis of aphid feeding behaviour. CONCLUSIONS:
      Analysis of transcriptional profiles of wt, aos and fou2 plants revealed that the
      expression of more than 200 genes is dependent on jasmonate status, regardless of
      external stimuli. Moreover, the aphid-induced response of more than 800
      transcripts is regulated by jasmonate signalling. Thus, in plants lacking
      jasmonates many of the defence-related responses induced by infestation in wt
      plants are impaired. Constant up-regulation of jasmonate signalling as evident in
      the fou2 mutant causes reduction in aphid population growth, likely as a result
      of antibiotic properties of fou2 plants. However, aos mutation does not seem to
      affect aphid performance when the density of B. brassicae populations on plants
      is low and aphids are free to move around.

PMID- 21854624
TI  - Signs and symptoms of acute mania: a factor analysis.
AB  - BACKGROUND: The major diagnostic classifications consider mania as a uni
      dimensional illness. Factor analytic studies of acute mania are fewer compared to
      schizophrenia and depression. Evidence from factor analysis suggests more
      categories or subtypes than what is included in the classification systems.
      Studies have found that these factors can predict differences in treatment
      response and prognosis. METHODS: The sample included 131 patients consecutively
      admitted to an acute psychiatry unit over a period of one year. It included 76
      (58%) males. The mean age was 44.05 years (SD = 15.6). Patients met International
      Classification of Diseases-10 (ICD-10) clinical diagnostic criteria for a manic
      episode. Patients with a diagnosis of mixed bipolar affective disorder were
      excluded. Participants were evaluated using the Young Mania Rating Scale (YMRS).
      Exploratory factor analysis (principal component analysis) was carried out and
      factors with an eigenvalue > 1 were retained. The significance level for
      interpretation of factor loadings was 0.40. The unrotated component matrix
      identified five factors. Oblique rotation was then carried out to identify three
      factors which were clinically meaningful. RESULTS: Unrotated principal component
      analysis extracted five factors. These five factors explained 65.36% of the total
      variance. Oblique rotation extracted 3 factors. Factor 1 corresponding to
      'irritable mania' had significant loadings of irritability, increased motor
      activity/energy and disruptive aggressive behaviour. Factor 2 corresponding to
      'elated mania' had significant loadings of elevated mood, language
      abnormalities/thought disorder, increased sexual interest and poor insight.
      Factor 3 corresponding to 'psychotic mania' had significant loadings of
      abnormalities in thought content, appearance, poor sleep and speech
      abnormalities. CONCLUSIONS: Our findings identified three clinically meaningful
      factors corresponding to 'elated mania', 'irritable mania' and 'psychotic mania'.
      These findings support the multidimensional nature of manic symptoms. Further
      evidence is needed to support the existence of corresponding clinical subtypes.

PMID- 21854625
TI  - Effect of short-acting beta blocker on the cardiac recovery after cardiopulmonary
      bypass.
AB  - The objective of this study was to investigate the effect of beta blocker on
      cardiac recovery and rhythm during cardiac surgeries. Sixty surgical rheumatic
      heart disease patients were received esmolol 1 mg/kg or the same volume of saline
      prior to removal of the aortic clamp. The incidence of cardiac automatic re-beat,
      ventricular fibrillation after reperfusion, the heart rate after steady re-beat,
      vasoactive drug use during weaning from bypass, the posterior parallel time and
      total bypass time were decreased by esmolol treatment. IN CONCLUSION: Esmolol has
      a positive effect on the cardiac recovery in cardiopulmonary bypass surgeries.

PMID- 21854626
TI  - Developing a predictive tool for psychological well-being among Chinese
      adolescents in the presence of missing data.
AB  - BACKGROUND: Multi-dimensional behavioral rating scales like the CBCL and YSR are
      available for diagnosing psychosocial maladjustment in adolescents, but these are
      unsuitable for large-scale usage since they are time-consuming and their many
      sensitive questions often lead to missing data. This research applies multiple
      imputation to tackle the effects of missing data in order to develop a simple
      questionnaire-based predictive instrument for psychosocial maladjustment.
      METHODS: Questionnaires from 2919 Chinese sixth graders in 21 schools were
      collected, but 86% of the students were missing one or more of the variables for
      analysis. Fifteen (10 training, 5 validation) samples were imputed using
      multivariate imputation chain equations. A ten-variable instrument was
      constructed by applying stepwise variable selection algorithms to the training
      samples, and its predictive performance was evaluated on the validation samples.
      RESULTS: The instrument had an AUC of 0.75 (95% CI: 0.73 to 0.78) and a
      calibration slope of 0.98 (95% CI: 0.86 to 1.09). The prevalence of psychosocial
      maladjustment was 18%. If a score of > 1 was used to define a negative test, then
      80% of the students would be classified as negative. The resulting test had a
      diagnostic odds ratio of 5.64 (95% CI: 4.39 to 7.24), with negative and positive
      predictive values of 88% and 43%, and negative and positive likelihood ratios of
      0.61 and 3.41, respectively. CONCLUSIONS: Multiple imputation together with
      internal validation provided a simple method for deriving a predictive instrument
      in the presence of missing data. The instrument's high negative predictive value
      implies that in populations with similar prevalences of psychosocial
      maladjustment test-negative students can be confidently excluded as being normal,
      thus saving 80% of the resources for confirmatory psychological testing.

PMID- 21854627
TI  - Engineering of an E. coli outer membrane protein FhuA with increased channel
      diameter.
AB  - BACKGROUND: Channel proteins like FhuA can be an alternative to artificial
      chemically synthesized nanopores. To reach such goals, channel proteins must be
      flexible enough to be modified in their geometry, i.e. length and diameter. As
      continuation of a previous study in which we addressed the lengthening of the
      channel, here we report the increasing of the channel diameter by genetic
      engineering. RESULTS: The FhuA Delta1-159 diameter increase has been obtained by
      doubling the amino acid sequence of the first two N-terminal beta-strands,
      resulting in variant FhuA Delta1-159 Exp. The total number of beta-strands
      increased from 22 to 24 and the channel surface area is expected to increase by
      ~16%. The secondary structure analysis by circular dichroism (CD) spectroscopy
      shows a high beta-sheet content, suggesting the correct folding of FhuA Delta1
      159 Exp. To further prove the FhuA Delta1-159 Exp channel functionality, kinetic
      measurement using the HRP-TMB assay (HRP = Horse Radish Peroxidase, TMB =
      3,3',5,5'-tetramethylbenzidine) were conducted. The results indicated a 17%
      faster diffusion kinetic for FhuA Delta1-159 Exp as compared to FhuA Delta1-159,
      well correlated to the expected channel surface area increase of ~16%.
      CONCLUSION: In this study using a simple "semi rational" approach the FhuA Delta1
      159 diameter was enlarged. By combining the actual results with the previous ones
      on the FhuA Delta1-159 lengthening a new set of synthetic nanochannels with
      desired lengths and diameters can be produced, broadening the FhuA Delta1-159
      applications. As large scale protein production is possible our approach can give
      a contribution to nanochannel industrial applications.

PMID- 21854629
TI  - Identification, structure, and characterization of an exopolysaccharide produced
      by Histophilus somni during biofilm formation.
AB  - BACKGROUND: Histophilus somni, a gram-negative coccobacillus, is an obligate
      inhabitant of bovine and ovine mucosal surfaces, and an opportunistic pathogen
      responsible for respiratory disease and other systemic infections in cattle and
      sheep. Capsules are important virulence factors for many pathogenic bacteria, but
      a capsule has not been identified on H. somni. However, H. somni does form a
      biofilm in vitro and in vivo, and the biofilm matrix of most bacteria consists of
      a polysaccharide. RESULTS: Following incubation of H. somni under growth
      restricting stress conditions, such as during anaerobiosis, stationary phase, or
      in hypertonic salt, a polysaccharide could be isolated from washed cells or
      culture supernatant. The polysaccharide was present in large amounts in broth
      culture sediment after H. somni was grown under low oxygen tension for 4-5 days
      (conditions favorable to biofilm formation), but not from planktonic cells during
      log phase growth. Immuno-transmission electron microscopy showed that the
      polysaccharide was not closely associated with the cell surface, and was of
      heterogeneous high molecular size by gel electrophoresis, indicating it was an
      exopolysaccharide (EPS). The EPS was a branched mannose polymer containing some
      galactose, as determined by structural analysis. The mannose-specific Moringa M
      lectin and antibodies to the EPS bound to the biofilm matrix, demonstrating that
      the EPS was a component of the biofilm. The addition of N-acetylneuraminic acid
      to the growth medium resulted in sialylation of the EPS, and increased biofilm
      formation. Real-time quantitative reverse transcription-polymerase chain reaction
      analyses indicated that genes previously identified in a putative polysaccharide
      locus were upregulated when the bacteria were grown under conditions favorable to
      a biofilm, compared to planktonic cells. CONCLUSIONS: H. somni is capable of
      producing a branching, mannose-galactose EPS polymer under growth conditions
      favorable to the biofilm phase of growth, and the EPS is a component of the
      biofilm matrix. The EPS can be sialylated in strains with sialyltransferase
      activity, resulting in enhanced density of the biofilm, and suggesting that EPS
      and biofilm formation may be important to persistence in the bovine host. The EPS
      may be critical to virulence if the biofilm state is required for H. somni to
      persist in systemic sites.

PMID- 21854630
TI  - Virtual environment to quantify the influence of colour stimuli on the
      performance of tasks requiring attention.
AB  - BACKGROUND: Recent studies indicate that the blue-yellow colour discrimination is
      impaired in ADHD individuals. However, the relationship between colour and
      performance has not been investigated. This paper describes the development and
      the testing of a virtual environment that is capable to quantify the influence of
      red-green versus blue-yellow colour stimuli on the performance of people in a fun
      and interactive way, being appropriate for the target audience. METHODS: An
      interactive computer game based on virtual reality was developed to evaluate the
      performance of the players.The game's storyline was based on the story of an old
      pirate who runs across islands and dangerous seas in search of a lost treasure.
      Within the game, the player must find and interpret the hints scattered in
      different scenarios. Two versions of this game were implemented. In the first,
      hints and information boards were painted using red and green colours. In the
      second version, these objects were painted using blue and yellow colours. For
      modelling, texturing, and animating virtual characters and objects the three
      dimensional computer graphics tool Blender 3D was used. The textures were created
      with the GIMP editor to provide visual effects increasing the realism and
      immersion of the players. The games were tested on 20 non-ADHD volunteers who
      were divided into two subgroups (A1 and A2) and 20 volunteers with ADHD who were
      divided into subgroups B1 and B2. Subgroups A1 and B1 used the first version of
      the game with the hints painted in green-red colors, and subgroups A2 and B2 the
      second version using the same hints now painted in blue-yellow. The time spent to
      complete each task of the game was measured. RESULTS: Data analyzed with ANOVA
      two-way and posthoc TUKEY LSD showed that the use of blue/yellow instead of
      green/red colors decreased the game performance of all participants. However, a
      greater decrease in performance could be observed with ADHD participants where
      tasks, that require attention, were most affected. CONCLUSIONS: The game proved
      to be a user-friendly tool capable to detect and quantify the influence of color
      on the performance of people executing tasks that require attention and showed to
      be attractive for people with ADHD.

PMID- 21854631
TI  - Common statistical and research design problems in manuscripts submitted to high
      impact medical journals.
AB  - BACKGROUND: To assist educators and researchers in improving the quality of
      medical research, we surveyed the editors and statistical reviewers of high
      impact medical journals to ascertain the most frequent and critical statistical
      errors in submitted manuscripts. FINDINGS: The Editors-in-Chief and statistical
      reviewers of the 38 medical journals with the highest impact factor in the 2007
      Science Journal Citation Report and the 2007 Social Science Journal Citation
      Report were invited to complete an online survey about the statistical and design
      problems they most frequently found in manuscripts. Content analysis of the
      responses identified major issues. Editors and statistical reviewers (n = 25)
      from 20 journals responded. Respondents described problems that we classified
      into two, broad themes: A. statistical and sampling issues and B. inadequate
      reporting clarity or completeness. Problems included in the first theme were (1)
      inappropriate or incomplete analysis, including violations of model assumptions
      and analysis errors, (2) uninformed use of propensity scores, (3) failing to
      account for clustering in data analysis, (4) improperly addressing missing data,
      and (5) power/sample size concerns. Issues subsumed under the second theme were
      (1) Inadequate description of the methods and analysis and (2) Misstatement of
      results, including undue emphasis on p-values and incorrect inferences and
      interpretations. CONCLUSIONS: The scientific quality of submitted manuscripts
      would increase if researchers addressed these common design, analytical, and
      reporting issues. Improving the application and presentation of quantitative
      methods in scholarly manuscripts is essential to advancing medical research.

PMID- 21854628
TI  - LIP expression is regulated by IGF-1R signaling and participates in suppression
      of anoikis.
AB  - BACKGROUND: The transcription factor, CCAAT enhancer binding protein-beta
      (C/EBPbeta), is expressed as several distinct protein isoforms (LAP1, LAP2 and
      LIP) that have opposing actions in cellular proliferation and differentiation.
      Increases in the ratio of LIP/LAP are associated with aggressive, metastatic
      breast cancer; however, little is known regarding the molecular mechanisms that
      regulate LIP expression or the biological actions of an increase in the LIP/LAP
      ratio. Metastasis is highly dependent upon the suppression of anoikis and the
      role of C/EBPbeta and LIP in this anchorage-independent, survival process is
      currently not known in mammary epithelial cells. IGF-1R signaling is important
      for the survival of breast cancer cells and crosstalk between IGF-1R and EGFR
      signaling pathways have been implicated in the development of more aggressive
      disease. We therefore evaluated in mammary epithelial cells whether IGF-1R
      signaling regulates the LIP/LAP ratio, analyzed the potential interplay between
      EGFR and IGF-1R signaling and addressed the biological significance of increased
      LIP expression in cellular survival and suppression of anoikis. RESULTS: Our data
      provide the first evidence that IGF-1R signaling regulates LIP expression in an
      EGFR independent manner to increase the LIP/LAP ratio in mammary epithelial
      cells. Although crosstalk between IGF-1R signaling and EGFR signaling is
      detectable in MCF10A cells, this crosstalk is not required for the IGF-1 mediated
      regulation of LIP expression. Rather, the critical regulator of IGF-1 induced LIP
      expression appears to be EGFR-independent, Akt activity. Our data also
      demonstrate that increases in LIP expression promote cell survival via
      suppression of anoikis. Likewise, knockdown of total C/EBPbeta leads to increased
      cell death and suggest that C/EBPbeta expression is important for survival and
      resistance to anoikis. IGF-1 treatment can partially rescue vector control cells
      from anoikis; however, cells with reduced C/EBPbeta expression do not survive
      anoikis. CONCLUSIONS: Taken together, our data demonstrate that IGF-1R signaling
      regulates LIP expression in an EGFR independent manner to increase the LIP/LAP
      ratio in mammary epithelial cells. C/EBPbeta expression and elevations in LIP
      play an important role in regulating cellular survival via suppression of
      anoikis, in an IGF-1R mediated context or in a manner independent of IGF-1R
      signaling.

PMID- 21854632
TI  - Post-traumatic diaphragmatic herniation of the liver, examined by positron
      emission tomography: case report.
AB  - We present a case of post-traumatic diaphragmatic herniation of the liver, which
      mimicked an intrathoracic tumor. After an automobile accident, the patient
      underwent thoracotomies for hemothorax and lung cancer in the right chest. Seven
      months later, computed tomography (CT) demonstrated a round tumor in the thorax
      adjacent to the right diaphragm with a higher density than the liver parenchyma.
      An intrathoracic tumor including a primary or metastatic lung cancer was
      suspected. However, positron emission tomography (PET) showed that the uptake of
      fluorine-18-fluorodeoxyglucose (FDG) was identical to that in the liver, and the
      tumor appeared to be contiguous with the liver. Thus, we suspected liver
      herniation. Core needle biopsy revealed liver cells without neoplastic tissue.
      Upon surgical exploration, herniation of the liver was found and repaired. PET
      was helpful in providing morphological and functional information leading to
      accurate diagnosis of liver herniation in this unusual case.

PMID- 21854633
TI  - Kbus/Idr, a mutant mouse strain with skeletal abnormalities and hypophosphatemia:
      identification as an allele of 'Hyp'.
AB  - BACKGROUND: The endopeptidase encoded by Phex (phosphate-regulating gene with
      homologies to endopeptidases linked to the X chromosome) is critical for
      regulation of bone matrix mineralization and phosphate homeostasis. PHEX has been
      identified from analyses of human X-linked hypophosphatemic rickets and Hyp
      mutant mouse models. We here demonstrated a newly established dwarfism-like
      Kbus/Idr mouse line to be a novel Hyp model. METHODS: Histopathological and X-ray
      examination with cross experiments were performed to characterize Kbus/Idr. RT
      PCR-based and exon-directed PCR screening performed to identify the presence of
      genetic alteration. Biochemical assays were also performed to evaluate activity
      of alkaline phosphatase. RESULTS: Kbus/Idr, characterized by bone mineralization
      defects, was found to be inherited in an X chromosome-linked dominant manner. RT
      PCR experiments showed that a novel mutation spanning exon 16 and 18 causing
      hypophosphatemic rickets. Alkaline phosphatase activity, as an osteoblast marker,
      demonstrated raised levels in the bone marrow of Kbus/Idr independent of the age.
      CONCLUSIONS: Kbus mice should serve as a useful research tool exploring molecular
      mechanisms underlying aberrant Phex-associated pathophysiological phenomena.

PMID- 21854634
TI  - Sustaining innovation in the health care workforce: a case study of community
      nurse consultant posts in England.
AB  - BACKGROUND: Recruiting, retaining and meeting increasing demand for experienced,
      qualified nurses is an issue of concern for all health care systems. The UK has
      been creating clinical career structures for nurses that include innovative posts
      known as nurse consultants. While the numbers overall appear to have grown over
      the last eleven years, there is evidence that in some specialities and regions
      the numbers are decreasing. This paper considers the factors that sustain or
      curtail workforce innovations through the case example of a cohort of nurse
      consultants established in one community health service in England. METHODS: A
      mixed method case study evaluation was undertaken over three years, using
      interviews, observations, documentary analysis and questionnaires. The final
      element of data collection was obtained three years later. Data was anonymised,
      analysed using a framework method and then integrated using a narrative
      synthesis. RESULTS: Ten nurse consultant posts were created over a period of two
      years (2002-2004). Within two years only five posts remained and within five
      years (2009) only two part time posts, with the original appointees, remained.
      When the nurse consultants left their posts, these were not replaced. In
      exploring the interaction between the innovation (the nurse consultant posts),
      the adoptees (the senior staff in the organisation) and the context (the
      immediate service colleagues, the service organisation and commissioners as well
      as the broader NHS policy context) three key factors were identified as
      influential in the demise of the posts. These were: a) the extent to which there
      was support for individual nurses rather than the post, b) the extent to which
      there was an unambiguous and uncontested clinical service requirement for a nurse
      consultant and c) the extent to which finances for the post were judged as being
      used to best effect in a service setting. CONCLUSIONS: This case study example
      demonstrates how tantalisingly close the nurse consultant initiative came to
      achieving a clinical career pathway for nurses in community services but more
      work was required to normalise clinician and managers' beliefs in the relevance
      and need for the role. Those looking to embed these types of nursing workforce
      innovations should pay due regard to these issues.

PMID- 21854635
TI  - Lipid rescue of massive verapamil overdose: a case report.
AB  - INTRODUCTION: Massive intentional verapamil overdose is a toxic ingestion which
      can cause multiorgan system failure and has no currently known antidote. CASE
      PRESENTATION: The patient is a 41-year-old Caucasian woman who ingested 19.2 g of
      sustained release verapamil in a suicide attempt. Our patient became hypotensive
      requiring three high-dose vasopressors to maintain arterial pressure. She also
      developed acute respiratory failure, bradycardic ventricular rhythm necessitating
      continuous transvenous pacing, and anuric renal failure. Our patient was treated
      with intravenous calcium, bicarbonate, hyperinsulinemic euglycemic therapy and
      continuous venovenous hemodialysis without success. On the fourth day after
      hospital admission continuous intravenous lipid therapy was initiated. Within
      three hours of beginning lipid therapy, our patient's vasopressor requirement
      decreased by half. Within 24 hours, she was on minimal vasopressor support and
      regained an underlying junctional rhythm. After three days of lipid infusion, she
      no longer required inotropic agents to maintain blood pressure or pacing to
      maintain stable hemodynamics. CONCLUSIONS: Intravenous fat emulsion therapy may
      be an effective antidote for massive verapamil toxicity.

PMID- 21854636
TI  - Intramedullary versus extramedullary alignment of the tibial component in the
      Triathlon knee.
AB  - BACKGROUND: Long term survivorship in total knee arthroplasty is significantly
      dependant on prosthesis alignment. Our aim was determine which alignment guide
      was more accurate in positioning of the tibial component in total knee
      arthroplasty. We also aimed to assess whether there was any difference in short
      term patient outcome. METHOD: A comparison of intramedullary versus
      extramedullary alignment jig was performed. Radiological alignment of tibial
      components and patient outcomes of 103 Triathlon total knee arthroplasties were
      analysed. RESULTS: Use of the intramedullary was found to be significantly more
      accurate in determining coronal alignment (p = 0.02) while use of the
      extramedullary jig was found to give more accurate results in sagittal alignment
      (p = 0.04). There was no significant difference in WOMAC or SF-36 at six months.
      CONCLUSION: Use of an intramedullary jig is preferable for positioning of the
      tibial component using this knee system.

PMID- 21854637
TI  - Determination of the melon chloroplast and mitochondrial genome sequences reveals
      that the largest reported mitochondrial genome in plants contains a significant
      amount of DNA having a nuclear origin.
AB  - BACKGROUND: The melon belongs to the Cucurbitaceae family, whose economic
      importance among vegetable crops is second only to Solanaceae. The melon has a
      small genome size (454 Mb), which makes it suitable for molecular and genetic
      studies. Despite similar nuclear and chloroplast genome sizes, cucurbits show
      great variation when their mitochondrial genomes are compared. The melon
      possesses the largest plant mitochondrial genome, as much as eight times larger
      than that of other cucurbits. RESULTS: The nucleotide sequences of the melon
      chloroplast and mitochondrial genomes were determined. The chloroplast genome
      (156,017 bp) included 132 genes, with 98 single-copy genes dispersed between the
      small (SSC) and large (LSC) single-copy regions and 17 duplicated genes in the
      inverted repeat regions (IRa and IRb). A comparison of the cucumber and melon
      chloroplast genomes showed differences in only approximately 5% of nucleotides,
      mainly due to short indels and SNPs. Additionally, 2.74 Mb of mitochondrial
      sequence, accounting for 95% of the estimated mitochondrial genome size, were
      assembled into five scaffolds and four additional unscaffolded contigs. An 84% of
      the mitochondrial genome is contained in a single scaffold. The gene-coding
      region accounted for 1.7% (45,926 bp) of the total sequence, including 51 protein
      coding genes, 4 conserved ORFs, 3 rRNA genes and 24 tRNA genes. Despite the
      differences observed in the mitochondrial genome sizes of cucurbit species,
      Citrullus lanatus (379 kb), Cucurbita pepo (983 kb) and Cucumis melo (2,740 kb)
      share 120 kb of sequence, including the predicted protein-coding regions.
      Nevertheless, melon contained a high number of repetitive sequences and a high
      content of DNA of nuclear origin, which represented 42% and 47% of the total
      sequence, respectively. CONCLUSIONS: Whereas the size and gene organisation of
      chloroplast genomes are similar among the cucurbit species, mitochondrial genomes
      show a wide variety of sizes, with a non-conserved structure both in gene number
      and organisation, as well as in the features of the noncoding DNA. The transfer
      of nuclear DNA to the melon mitochondrial genome and the high proportion of
      repetitive DNA appear to explain the size of the largest mitochondrial genome
      reported so far.

PMID- 21854638
TI  - In vitro cytotoxicity of two novel oral formulations of Amphotericin B (iCo-009
      and iCo-010) against Candida albicans, human monocytic and kidney cell lines.
AB  - BACKGROUND: Invasive fungal infections such as candidiasis constitute an
      increasingly important medical problem. Drugs currently used for the treatment of
      candidiasis include polyenes (such as Amphotericin B) and azoles. Amphotericin B
      (AmpB) presents several limitations such as its nephrotoxicity and limited
      solubility. We have developed two novel lipid-based AmpB formulations which in
      vivo show less nephrotoxicity and enhanced solubility compared to FungizoneTM a
      commercial AmpB formulation. The purpose of this study was to determine the
      cytotoxicity of FungizoneTM, AmbisomeTM and two novel AmpB formulations (iCo-009
      and iCo-010) against Candida albicans, human kidney (293T) cells and monocytic
      (THP1) cells. METHODS: Cell cytotoxicity to the AmpB formulations was evaluated
      by MTS and LDH assays. In vitro anti-Candida albicans activity was assessed after
      a 48 h drug incubation. RESULTS: None of the AmpB formulations tested showed
      cytotoxicity against 293T cells. In the case of THP1 cells only FungizoneTM and
      AmbisomeTM showed cytotoxicity at 500 MUg/L (n = 4-10, p < 0.05).The calculated
      EC50 to Candida albicans for the different formulations was as follows: 26.8 +/-
      2.9 for iCo-010, 74.6 +/- 8.9 for iCo-009, 109 +/- 31 for AmbisomeTM and 87.1 +/-
      22 for FungizoneTM (MUg of AmpB/L, n = 6-12, p < 0.05). CONCLUSIONS: The AmpB
      formulations analyzed were not cytotoxic to 293T cells. Cytotoxicity in THP1
      cells was observed for FungizoneTM and AmbisomeTM, but not with the novel AmpB
      formulations. iCo-010 had higher efficacy compared to other three AmpB
      formulations in the Candida albicans model.The absence of cytotoxicity as well as
      its higher efficacy for the Candida model compared to FungizoneTM and AmbisomeTM
      suggest that iCo-010 has potential in treating candidiasis.

PMID- 21854639
TI  - Fractal dimension approach in postural control of subjects with Prader-Willi
      Syndrome.
AB  - BACKGROUND: Static posturography is user-friendly technique suitable for the
      study of the centre of pressure (CoP) trajectory. However, the utility of static
      posturography in clinical practice is somehow limited and there is a need for
      reliable approaches to extract physiologically meaningful information from
      stabilograms. The aim of this study was to quantify the postural strategy of
      Prader-Willi patients with the fractal dimension technique in addition to the CoP
      trajectory analysis in time and frequency domain. METHODS: 11 adult patients
      affected by Prader-Willi Syndrome (PWS) and 20 age-matched individuals ( CONTROL
      GROUP: CG) were included in this study. Postural acquisitions were conducted by
      means of a force platform and the participants were required to stand barefoot on
      the platform with eyes open and heels at standardized distance and position for
      30 seconds. Platform data were analysed in time and frequency domain. Fractal
      Dimension (FD) was also computed. RESULTS: The analysis of CoP vs. time showed
      that in PWS participants all the parameters were statistically different from CG,
      with greater displacements along both the antero-posterior and medio-lateral
      direction and longer CoP tracks. As for frequency analysis, our data showed no
      significant differences between PWS and CG. FD evidenced that PWS individuals
      were characterized by greater value in comparison with CG. CONCLUSIONS: Our data
      showed that while the analysis in the frequency domain did not seem to explain
      the postural deficit in PWS, the FD method appears to provide a more informative
      description of it and to complement and integrate the time domain analysis.

PMID- 21854640
TI  - Reirradiation of head and neck cancer focusing on hypofractionated stereotactic
      body radiation therapy.
AB  - Reirradiation is a feasible option for patients who do not otherwise have
      treatment options available. Depending on the location and extent of the tumor,
      reirradiation may be accomplished with external beam radiotherapy, brachytherapy,
      radiosurgery, or intensity modulated radiation therapy (IMRT). Although there has
      been limited experience with hypofractionated stereotactic radiotherapy (hSRT),
      it may have the potential for curative or palliative treatment due to its
      advanced precision technology, particularly for limited small lesion. On the
      other hand, severe late adverse reactions are anticipated with reirradiation than
      with initial radiation therapy. The risk of severe late complications has been
      reported to be 20- 40% and is related to prior radiotherapy dose, primary site,
      retreatment radiotherapy dose, treatment volume, and technique. Early researchers
      have observed lethal bleeding in such patients up to a rate of 14%. Recently,
      similar rate of 10-15% was observed for fatal bleeding with use of modern hSRT
      like in case of carotid blowout syndrome. To determine the feasibility and
      efficacy of reirradiation using modern technology, we reviewed the pertinent
      literature. The potentially lethal side effects should be kept in mind when
      reirradiation by hSRT is considered for treatment, and efforts should be made to
      minimize the risk in any future investigations.

PMID- 21854641
TI  - Measuring the equity of inpatient utilization in Chinese rural areas.
AB  - BACKGROUND: As an important outcome of the health system, equity in health
      service utilization has attracted an increasing amount of attention in the
      literature on health reform in China in recent years. The poor, who frequently
      require more services, are often the least able to pay, while the wealthy utilize
      disproportionately more services although they have less need. Whereas equity in
      health service utilization between richer and poorer populations has been studied
      in urban areas, the equity in health service utilization in rural areas has
      received little attention. With improving levels of economic development, the
      introduction of health insurance and increasing costs of health services, health
      service utilization patterns have changed dramatically in rural areas in recent
      years. However, previous studies have shown neither the extent of utilization
      inequity, nor which factors are associated with utilization inequity in rural
      China. METHODS: This paper uses previously unavailable country-wide data and
      focuses on income-related inequity of inpatient utilization and its determinants
      in Chinese rural areas. The data for this study come from the Chinese National
      Health Services Surveys (NHSS) conducted in 2003 and 2008. To measure the level
      of inequity in inpatient utilization over time, the concentration index,
      decomposition of the concentration index, and decomposition of change in the
      concentration index are employed. RESULTS: This study finds that even with the
      same need for inpatient services, richer individuals utilize more inpatient
      services than poorer individuals. Income is the principal determinant of this pro
      rich inpatient utilization inequity- wealthier individuals are able to pay for
      more services and therefore use more services regardless of need. However, rising
      income and increased health insurance coverage have reduced the inequity in
      inpatient utilization in spite of increasing inpatient prices. CONCLUSIONS: There
      remains a strong pro-rich inequity of inpatient utilization in rural China.
      However, a narrowing income gap between the rich and poor and greater access to
      health insurance has effectively reduced income inequality, equalizing access to
      care. This suggests that the most effective way to reduce the inequity is to
      narrow the gap of income between the rich and poor while adopting social risk
      protection.

PMID- 21854642
TI  - Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen:
      baseline data and implications.
AB  - BACKGROUND: This is an investigation of anti-malarial molecular markers coupled
      with a therapeutic efficacy test of chloroquine (CQ) against falciparum malaria
      in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at
      assessment of therapeutic response to CQ and elucidation of baseline information
      on molecular markers for Plasmodium falciparum resistance against CQ and
      sulphadoxine/pyrimethamine (SP). METHODS: Between 2002 and 2003 the field test
      was conducted according to the standard WHO protocol to evaluate the therapeutic
      efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj
      Governorate in Yemen. Blood samples collected during this study were analysed for
      P. falciparum chloroquine resistance transporter gene (pfcrt)-76 polymorphisms,
      mutation pfcrt-S163R and the antifolate resistance-associated mutations
      dihydrofolate reductase (dhfr)-C59R and dihydropteroate synthase (dhps)-K540E.
      Direct DNA sequencing of the pfcrt gene from three representative field samples
      was carried out after DNA amplification of the 13 exons of the pfcrt gene.
      RESULTS: Treatment failure was detected in 61% of the 122 cases that completed
      the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified
      pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo
      CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9). The prevalence of dhfr Arg-59
      mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected
      in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni
      CQ resistant P. falciparum carry the old world (Asian and African) CQ resistant
      haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. CONCLUSION:
      This is the first study to report baseline information on the characteristics and
      implications of anti-malarial drug resistance markers in Yemen. It is also the
      first report of the haplotype associated with CQR P. falciparum parasites from
      Yemen. Mutant pfcrtT76 is highly prevalent but it is a poor predictor of
      treatment failure in the study population. The prevalence of mutation dhfrArg59
      is suggestive of emerging resistance to SP, which is currently a component of the
      recommended combination treatment of falciparum malaria in Yemen. More studies on
      these markers are recommended for surveillance of resistance in the study area.

PMID- 21854643
TI  - [Cost] effectiveness of withdrawal of fall-risk increasing drugs versus
      conservative treatment in older fallers: design of a multicenter randomized
      controlled trial (IMPROveFALL-study).
AB  - BACKGROUND: Fall incidents represent an increasing public health problem in aging
      societies worldwide. A major risk factor for falls is the use of fall-risk
      increasing drugs. The primary aim of the study is to compare the effect of a
      structured medication assessment including the withdrawal of fall-risk increasing
      drugs on the number of new falls versus 'care as usual' in older adults
      presenting at the Emergency Department after a fall. METHODS/DESIGN: A
      prospective, multi-center, randomized controlled trial will be conducted in
      hospitals in the Netherlands. Persons aged >=65 years who visit the Emergency
      Department due to a fall are invited to participate in this trial. All patients
      receive a full geriatric assessment at the research outpatient clinic. Patients
      are randomized between a structured medication assessment including withdrawal of
      fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is
      used for assessing the number of falls, fallers and associated injuries over a
      one-year follow-up period. Measurements will be at three, six, nine, and twelve
      months and include functional outcome, healthcare consumption, socio-demographic
      characteristics, and clinical information. After twelve months a second visit to
      the research outpatient clinic will be performed, and adherence to the new
      medication regimen in the intervention group will be measured. The primary
      outcome will be the incidence of new falls. Secondary outcome measurements are
      possible health effects of medication withdrawal, health-related quality of life
      (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the
      intervention. Data will be analyzed using an intention-to-treat analysis.
      DISCUSSION: The successful completion of this trial will provide evidence on the
      effectiveness of withdrawal of fall-risk increasing drugs in older patients as a
      method for falls reduction. TRIAL REGISTRATION: The trial is registered in the
      Netherlands Trial Register (NTR1593).

PMID- 21854644
TI  - Cognitive functioning in opioid-dependent patients treated with buprenorphine,
      methadone, and other psychoactive medications: stability and correlates.
AB  - BACKGROUND: In many but not in all neuropsychological studies buprenorphine
      treated opioid-dependent patients have shown fewer cognitive deficits than
      patients treated with methadone. In order to examine if hypothesized cognitive
      advantage of buprenorphine in relation to methadone is seen in clinical patients
      we did a neuropsychological follow-up study in unselected sample of buprenorphine
      vs. methadone-treated patients. METHODS: In part I of the study fourteen
      buprenorphine-treated and 12 methadone-treated patients were tested by cognitive
      tests within two months (T1), 6-9 months (T2), and 12-17 months (T3) from the
      start of opioid substitution treatment. Fourteen healthy controls were examined
      at similar intervals. Benzodiazepine and other psychoactive comedications were
      common among the patients. Test results were analyzed with repeated measures
      analysis of variance and planned contrasts. In part II of the study the patient
      sample was extended to include 36 patients at T2 and T3. Correlations between
      cognitive functioning and medication, substance abuse, or demographic variables
      were then analyzed. RESULTS: In part I methadone patients were inferior to
      healthy controls tests in all tests measuring attention, working memory, or
      verbal memory. Buprenorphine patients were inferior to healthy controls in the
      first working memory task, the Paced Auditory Serial Addition Task and verbal
      memory. In the second working memory task, the Letter-Number Sequencing, their
      performance improved between T2 and T3. In part II only group membership
      (buprenorphine vs. methadone) correlated significantly with attention performance
      and improvement in the Letter-Number Sequencing. High frequency of substance
      abuse in the past month was associated with poor performance in the Letter-Number
      Sequencing. CONCLUSIONS: The results underline the differences between non
      randomized and randomized studies comparing cognitive performance in opioid
      substitution treated patients (fewer deficits in buprenorphine patients vs. no
      difference between buprenorphine and methadone patients, respectively). Possible
      reasons for this are discussed.

PMID- 21854646
TI  - Colour break in reverse bicolour daffodils is associated with the presence of
      Narcissus mosaic virus.
AB  - BACKGROUND: Daffodils (Narcissus pseudonarcissus) are one of the world's most
      popular ornamentals. They also provide a scientific model for studying the
      carotenoid pigments responsible for their yellow and orange flower colours. In
      reverse bicolour daffodils, the yellow flower trumpet fades to white with age.
      The flowers of this type of daffodil are particularly prone to colour break
      whereby, upon opening, the yellow colour of the perianth is observed to be
      'broken' into patches of white. This colour break symptom is characteristic of
      potyviral infections in other ornamentals such as tulips whose colour break is
      due to alterations in the presence of anthocyanins. However, reverse bicolour
      flowers displaying colour break show no other virus-like symptoms such as leaf
      mottling or plant stunting, leading some to argue that the carotenoid-based
      colour breaking in reverse bicolour flowers may not be caused by virus infection.
      RESULTS: Although potyviruses have been reported to cause colour break in other
      flower species, enzyme-linked-immunoassays with an antibody specific to the
      potyviral family showed that potyviruses were not responsible for the occurrence
      of colour break in reverse bicolour daffodils. Colour break in this type of
      daffodil was clearly associated with the presence of large quantities of rod
      shaped viral particles of lengths 502-580 nm in tepals. Sap from flowers
      displaying colour break caused red necrotic lesions on Gomphrena globosa,
      suggesting the presence of potexvirus. Red necrotic lesions were not observed in
      this indicator plant when sap from reverse bicolour flowers not showing colour
      break was used. The reverse transcriptase polymerase reactions using degenerate
      primers to carla-, potex- and poty-viruses linked viral RNA with colour break and
      sequencing of the amplified products indicated that the potexvirus Narcissisus
      mosaic virus was the predominant virus associated with the occurrence of the
      colour break. CONCLUSIONS: High viral counts were associated with the reverse
      bicolour daffodil flowers that were displaying colour break but otherwise showed
      no other symptoms of infection. Narcissus mosaic virus was the virus that was
      clearly linked to the carotenoid-based colour break.

PMID- 21854645
TI  - Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in
      head and neck squamous cell carcinomas.
AB  - BACKGROUND: Chronic inflammation plays an important role in head and neck
      squamous cell carcinomas (HNSCC). This study addresses the impact of two single
      nucleotide polymorphisms (SNP) Asp299Gly and Thr399Ile of the toll-like receptor
      (TLR) 4 gene on the clinical outcome while accounting for the influence of
      adjuvant systemic therapy in a large cohort of HNSCC patients. METHODS: Genotype
      analysis was done using DNA from tissue samples from 188 patients with HNSCC;
      TLR4 protein expression was assessed immunohistochemically in tissue microarrays.
      Classical survival models were used for statistical analyses. RESULTS: Ten
      percent of patients with HNSCC presented with the TLR4 299Gly and 17% with the
      TLR4 399Ile allele. Patients with the heterozygous genotype TLR4 Asp299Gly had a
      significantly reduced disease-free and overall survival. Also, patients with the
      heterozygous genotype TLR4 Thr399Ile had a reduced disease-free survival.
      Notably, these associations seem to be attributable to relatively poor therapy
      response as e.g. reflected in a significantly shorter DFS among HNSCC patients
      carrying the Asp299Gly variant and receiving adjuvant systemic therapy.
      CONCLUSION: According to this study, TLR4 299Gly und 399Ile alleles may serve as
      markers for prognosis of head and neck cancer in patients with adjuvant systemic
      therapy, particularly chemotherapy, and might indicate therapy resistance.

PMID- 21854647
TI  - Anterior cingulate cortex is crucial for contra- but not ipsi-lateral electro
      acupuncture in the formalin-induced inflammatory pain model of rats.
AB  - Acupuncture and electro-acupuncture (EA) are now widely used to treat disorders
      like pain. We and others have shown previously that current frequency, intensity
      and treatment duration all significantly influence the anti-nociceptive effects
      of EA. There is evidence that stimulating sites also affect the antinociception,
      with EA applied ipsilaterally to the pain site being more effective under some
      pain states but contralateral EA under others. It was recently reported that
      local adenosine A1 receptors were responsible for ipsilateral acupuncture, but
      what mechanisms specifically mediate the anti-nociceptive effects of
      contralateral acupuncture or EA remains unclear. In the present study, we applied
      100 Hz EA on the ipsi- or contra-lateral side of rats with inflammatory pain
      induced by intra-plantar injection of formalin, and reported distinct anti
      nociceptive effects and mechanisms between them. Both ipsi- and contra-lateral EA
      reduced the paw lifting time in the second phase of the formalin test and
      attenuated formalin-induced conditioned place aversion. Contralateral EA had an
      additional effect of reducing paw licking time, suggesting a supraspinal
      mechanism. Lesions of rostral anterior cingulate cortex (ACC) completely
      abolished the anti-nociceptive effects of contra- but not ipsi-lateral EA. These
      findings were not lateralized effects, since injection of formalin into the left
      or right hind paws produced similar results. Overall, these results demonstrated
      distinct anti-nociceptive effects and mechanisms between different stimulating
      sides and implied the necessity of finding the best stimulating protocols for
      different pain states.

PMID- 21854648
TI  - Endothelial-like cells in chronic thromboembolic pulmonary hypertension:
      crosstalk with myofibroblast-like cells.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is
      characterized by intravascular thrombus formation in the pulmonary
      arteries.Recently, it has been shown that a myofibroblast cell phenotype was
      predominant within endarterectomized tissues from CTEPH patients. Indeed, our
      recent study demonstrated the existence of not only myofibroblast-like cells
      (MFLCs), but also endothelial-like cells (ELCs). Under in vitro conditions, a few
      transitional cells (co-expressing both endothelial- and SM-cell markers) were
      observed in the ELC population. We hypothesized that MFLCs in the
      microenvironment created by the unresolved clot may promote the endothelial
      mesenchymal transition and/or induce endothelial cell (EC) dysfunction. METHODS:
      We isolated cells from these tissues and identified them as MFLCs and ELCs. In
      order to test whether the MFLCs provide the microenvironment which causes EC
      alterations, ECs were incubated in serum-free medium conditioned by MFLCs, or
      were grown in co-culture with the MFLCs. RESULTS: Our experiments demonstrated
      that MFLCs promoted the commercially available ECs to transit to other
      mesenchymal phenotypes and/or induced EC dysfunction through inactivation of
      autophagy, disruption of the mitochondrial reticulum, alteration of the SOD-2
      localization, and decreased ROS production. Indeed, ELCs included a few
      transitional cells, lost the ability to form autophagosomes, and had defective
      mitochondrial structure/function. Moreover, rapamycin reversed the phenotypic
      alterations and the gene expression changes in ECs co-cultured with MFLCs, thus
      suggesting that this agent had beneficial therapeutic effects on ECs in CTEPH
      tissues. CONCLUSIONS: It is possible that the microenvironment created by the
      stabilized clot stimulates MFLCs to induce EC alterations.

PMID- 21854649
TI  - Subtype distribution of lymphomas in Southwest China: analysis of 6,382 cases
      using WHO classification in a single institution.
AB  - BACKGROUND: The subtype distribution of lymphoid neoplasms in Southwest China was
      analyzed according to WHO classifications. This study aims to analyze subtype
      distribution of lymphomas in southwest China. METHODS: Lymphoid neoplasms
      diagnosed within 9 years in a single institution in Southwest China were analyzed
      according to the WHO classification. RESULTS: From January 2000 to December 2008,
      a total number of 6,382 patients with lymphoma were established, of which mature
      B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%,
      and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%,
      respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin
      lymphoma; and the bimodal age distribution was not observed. The top six subtypes
      of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma,
      extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of
      mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid
      neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma.
      Extranodal lymphomas comprised about half of all cases, and most frequently
      involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin.
      CONCLUSIONS: The lymphoid neoplasms of Southwest China displayed some
      epidemiologic features similar to those reported in literature from western and
      Asian countries, as well as other regions of China, whereas some subtypes showed
      distinct features. The high frequency of mature T/NK cell neoplasms and
      extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type,
      is the most outstanding characteristic of this series.

PMID- 21854650
TI  - Incorporation of EPA and DHA into plasma phospholipids in response to different
      omega-3 fatty acid formulations--a comparative bioavailability study of fish oil
      vs. krill oil.
AB  - BACKGROUND: Bioavailability of omega-3 fatty acids (FA) depends on their chemical
      form. Superior bioavailability has been suggested for phospholipid (PL) bound
      omega-3 FA in krill oil, but identical doses of different chemical forms have not
      been compared. METHODS: In a double-blinded crossover trial, we compared the
      uptake of three EPA+DHA formulations derived from fish oil (re-esterified
      triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes
      of the FA compositions in plasma PL were used as a proxy for bioavailability.
      Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given
      either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose
      and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the
      proportion of free EPA and DHA in the applied supplements was analyzed. RESULTS:
      The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil
      (mean AUC0-72 h: 80.03 +/- 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h:
      59.78 +/- 36.75%*h) and EE (mean AUC0-72 h: 47.53 +/- 38.42%*h). Due to high
      standard deviation values, there were no significant differences for DHA and the
      sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057)
      was observed for the differences in EPA bioavailability. Statistical pair-wise
      group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA
      analysis of the supplements showed that the krill oil sample contained 22% of the
      total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while
      the two fish oil samples did not contain any free FA. CONCLUSION: Further studies
      with a larger sample size carried out over a longer period are needed to
      substantiate our findings and to determine differences in EPA+DHA bioavailability
      between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The
      unexpected high content of free EPA and DHA in krill oil, which might have a
      significant influence on the availability of EPA+DHA from krill oil, should be
      investigated in more depth and taken into consideration in future trials.

PMID- 21854651
TI  - Lipomatous apocrine adenoma with syringocystadenoma papilliferum arising from the
      external auditory canal.
AB  - A case of lipomatous tubular adenoma (LTA) with syringocystadenom papilliferum
      (SCAP) arising from the external auditory canal in a 25-year-old man is described
      and to the best of our knowledge through literature review, this kind of
      morphologic entity has not been reported before. Herein we reported the first
      case in the English literature in the world.

PMID- 21854652
TI  - Haplo2Ped: a tool using haplotypes as markers for linkage analysis.
AB  - BACKGROUND: Generally, SNPs are abundant in the genome; however, they display low
      power in linkage analysis because of their limited heterozygosity. Haplotype
      markers, on the other hand, which are composed of many SNPs, greatly increase
      heterozygosity and have superiority in linkage statistics. RESULTS: Here we
      developed Haplo2Ped to automatically transform SNP data into haplotype markers
      and then to compute the logarithm (base 10) of odds (LOD) scores of regional
      haplotypes that are homozygous within the disease co-segregation haploid group.
      The results are reported as a hypertext file and a 3D figure to help users to
      obtain the candidate linkage regions. The hypertext file contains parameters of
      the disease linked regions, candidate genes, and their links to public databases.
      The 3D figure clearly displays the linkage signals in each chromosome. We tested
      Haplo2Ped in a simulated SNP dataset and also applied it to data from a real
      study. It successfully and accurately located the causative genomic regions.
      Comparison of Haplo2Ped with other existing software for linkage analysis further
      indicated the high effectiveness of this software. CONCLUSIONS: Haplo2Ped uses
      haplotype fragments as mapping markers in whole genome linkage analysis. The
      advantages of Haplo2Ped over other existing software include straightforward
      output files, increased accuracy and superior ability to deal with pedigrees
      showing incomplete penetrance. Haplo2Ped is freely available at:
      http://bighapmap.big.ac.cn/software.html.

PMID- 21854653
TI  - Introduction of non-linear elasticity models for characterization of shape and
      deformation statistics: application to contractility assessment of isolated adult
      cardiocytes.
AB  - BACKGROUND: We are exploring the viability of a novel approach to cardiocyte
      contractility assessment based on biomechanical properties of the cardiac cells,
      energy conservation principles, and information content measures. We define our
      measure of cell contraction as being the distance between the shapes of the
      contracting cell, assessed by the minimum total energy of the domain deformation
      (warping) of one cell shape into another. To guarantee a meaningful vis-a-vis
      correspondence between the two shapes, we employ both a data fidelity term and a
      regularization term. The data fidelity term is based on nonlinear features of the
      shapes while the regularization term enforces the compatibility between the shape
      deformations and that of a hyper-elastic material. RESULTS: We tested the
      proposed approach by assessing the contractile responses in isolated adult rat
      cardiocytes and contrasted these measurements against two different methods for
      contractility assessment in the literature. Our results show good qualitative and
      quantitative agreements with these methods as far as frequency, pacing, and
      overall behavior of the contractions are concerned. CONCLUSIONS: We hypothesize
      that the proposed methodology, once appropriately developed and customized, can
      provide a framework for computational cardiac cell biomechanics that can be used
      to integrate both theory and experiment. For example, besides giving a good
      assessment of contractile response of the cardiocyte, since the excitation
      process of the cell is a closed system, this methodology can be employed in an
      attempt to infer statistically significant model parameters for the constitutive
      equations of the cardiocytes.

PMID- 21854654
TI  - [A white woman with white skin spots].
AB  - A 26-year-old white woman came to the clinic because of white spots. The spots
      were confluent in the midline, non-scaly and localized on trunk and proximal
      parts of the arms. Biopsy showed loss of pigment in the epidermis. The diagnosis
      was: progressive macular hypomelanosis.

PMID- 21854655
TI  - [Endovenous mechanochemical ablation for varicose veins--a new endovenous
      technique without tumescent anaesthesia].
AB  - In the past decades, endovenous techniques have played an increasingly important
      role in the treatment of varicose veins. The method of action of these techniques
      is based on heat, making tumescent anesthesia necessary. Despite this anesthesia,
      heat-induced complications such as skin burns, nerve damage and prolonged pain
      may occur. Endovenous mechanochemical ablation, in contrast, utilises an infusion
      catheter with a rotating tip. Obliteration of the insufficient vein is achieved
      both by mechanical destruction to the endothelium and by the fibrosing effect of
      a sclerosant. Tumescent anaesthesia can be omitted during this ablation
      technique, which makes it quicker and less painful than other endovenous
      treatments. This new technique is safe and has shown to be effective in the short
      term, with high satisfaction rates in treated patients.

PMID- 21854656
TI  - [Ocular myasthenia gravis: diagnosis often delayed].
AB  - When a patient complains of a fluctuating ptosis or diplopia the diagnosis
      'ocular myasthenia gravis' must be considered. The diagnosis can be difficult
      because of the subtle symptoms and less sensitive diagnostic testing. Because of
      this, there is often a patient and doctors delay. We describe 3 patients, a 63
      year-old man, a 49-year-old woman and a 77-year-old woman, who received the right
      diagnosis only after 22 months, 4 months and even 9 years after the first symptom
      occurred. At the neurological examination the provocation tests are of high
      importance. Confirmation of the diagnosis can be established with the following
      diagnostic procedures: neostigmine test, serological testing for antibodies
      against acetylcholine receptors and single fibre EMG.

PMID- 21854658
TI  - [A measurable connection between preventative interventions and the incidence of
      postoperative wound infection].
AB  - OBJECTIVE: To establish whether there was a link between the preventative
      interventions executed and two groups of patients: those with and those without a
      postoperative wound infection (POWI). DESIGN: Descriptive and comparative
      research. METHOD: At Rijnland Hospital, a Dutch non-academic teaching hospital,
      284 indicator operations were carried out between 1 April 2009 and 31 March 2010.
      We investigated whether preventative interventions were carried out during these
      operations. The types of surgery included mastectomy with and without axillary
      node dissection, resection of the colon and central vascular surgery
      (reconstruction of the aorta via an endovascular or open approach). Four types of
      intervention were studied: hygienic discipline (measurement of the number of
      times the operating theatre doors moved), the timely administration of
      preoperative antibiotic prophylactics, the avoidance of preoperative shaving and
      the attempts at perioperative normothermia. A 'postoperative wound infection' was
      registered as such if it had developed within 30 days of surgery. RESULTS: In
      total, 22 POWIs (7.7%) were registered, arising from 284 operations: 5 POWIs
      (2.8%) after mammary surgery, 1 POWI (2.8%) after central vascular surgery, and
      16 POWIs (21.6%) after colon surgery, respectively (see table 2). Meeting the
      criteria of all 4 types of intervention had no influence on the development of a
      POWI. A significant association to the development of a POWI was, however,
      determined to be the variables related to wound classification, duration of
      surgery and the average number of door movements per hour during surgery;
      specifically, 7 or more. CONCLUSION: Surveillance by way of registration and
      feedback of interventions and their optimisation, particularly in terms of door
      movement, can possibly contribute to a reduction in the number of postoperative
      would infections.

PMID- 21854659
TI  - [Guideline for diagnosis and treatment of acute inversion trauma of the ankle in
      athletes].
AB  - This multidisciplinary guideline has been developed as an aid to diagnosis and
      treatment of patients, especially athletes, with an acute inversion trauma of the
      ankle. Diagnosis of an acute inversion trauma is by means of a combination of
      location of the swelling, palpation and executing an anterior drawer test. X-rays
      are only indicated if weight-bearing is not possible and palpation of specific
      areas according to the 'Ottawa ankle rules' causes pain. Physical diagnostic
      examination 4-5 days post-trauma is a reliable method for discriminating between
      ankle sprain and lateral ligament rupture.- Rest, application of ice, compression
      and elevation (RICE) during the first days post-trauma is recommended. Analgesic
      therapy, with paracetamol as medication of choice, should be restricted to 2-7
      days post-trauma. Conservative treatment is preferential to surgical treatment. A
      semi-rigid brace protection should become a standard treatment procedure.
      Exercise therapy results in a faster recovery and a faster resumption of work and
      sporting activities. Exercises to improve proprioception, coordination and muscle
      strength are indicated.

PMID- 21854662
TI  - [Lipoblastoma and lipoblastomatosis: especially in children].
AB  - Lipoblastoma and lipoblastomatosis are rare benign fatty tumours that mainly
      occur in children under the age of 3 years. Several body sites can be affected.
      The term 'lipoblastoma' is reserved for an encapsulated neoplasm;
      'lipoblastomatosis' for tumours demonstrating infiltrative growth. Most of the
      clinical symptoms arise from a mass effect of the tumour on surrounding tissues.
      The tumours should be differentiated from lipoma, myxoid liposarcoma and
      hibernoma. A clear distinction can be made by cytogenetic analysis, since each of
      these tumours is known for its own typical genetic abnormalities. In lipoblastoma
      and lipoblastomatosis, these include a breakpoint in the 8q11-13 region or
      polysomy of chromosome 8, both leading to the activation of the oncogenic
      pleomorphic adenoma gene 1 (PLAG1) on 8q12. Treatment consists of surgical
      resection; there is no need for radiotherapy or chemotherapy. Clinical outcome
      depends on the completeness of the resection and damage that is done to the
      surrounding tissues during surgery.

PMID- 21854663
TI  - [Comprehensive quality indicators for measuring hospital antibiotic use].
AB  - As in other countries, the growing resistance to antimicrobial drugs is also
      taking place in the Netherlands; the primary cause being the total consumption of
      antibiotics. Given the steady decline in the discovery of new antimicrobials,
      better use of agents currently available is warranted. Guidelines describing
      appropriate antimicrobial therapy play an important role; however, such
      guidelines are not optimally used in daily practice. Quality indicators can be
      used to assess the quality of antibiotic treatment and evaluate the impact of
      interventions aimed at improving care. Quality indicators used for evaluating
      treatment of infections of the respiratory and urinary tracts are developed
      previously. A comprehensive set of indicators that could be used to assess the
      quality of hospital antibiotic use for all bacterial infections has not yet been
      developed. A new project has recently been started in the Netherlands called 'The
      development of Reliable generic quality Indicators for the optimalisation of
      ANTibiotic use in the hospital' (RIANT study) for developing such a set of
      comprehensive indicators.

PMID- 21854664
TI  - [Weak ankles...].
AB  - A new multidisciplinary guideline has been created to address the high incidence
      of acute inversion trauma of the ankle and the high number of patients with
      persistent symptoms and recurrence. Although the guideline's aim is to decrease
      the number of persistent symptoms and recurrence, risk- analysis of these post
      traumatic symptoms is lacking. Treatment is the same for all athletes: anyone who
      sustains an inversion trauma needs a semi-rigid brace and exercise therapy. It is
      remarkable that there is almost no evidence to support this and other
      recommendations. The research studies referred to in the articles are of moderate
      quality; good RCTs are missing. Based on this guideline, therefore, doctors,
      physiotherapists and patients are basically expected to do a lot of hoping that
      weak ankles will be prevented. This guideline makes it clear that there is great
      deal of good research needed in this branch of medicine. Given the target group,
      healthy athletes without a lot of co-morbidity, it would seem that this were
      possible.

PMID- 21854665
TI  - [Hepatitis B; sometimes co-infection with hepatitis D].
AB  - BACKGROUND: The Hepatitis delta virus (HDV) is a defect RNA virus that requires
      the presence of the hepatitis B virus (HBV) for cellular infection. Worldwide,
      350 million people are infected with HBV; 5% of these are superinfected with HDV.
      A chronic superinfection with HDV has a higher morbidity and mortality rate. It
      is clinically difficult to differentiate between an HBV and an HDV infection.
      Diagnosis is made via detection of HDV antibodies and HDV-RNA using PCR
      techniques. The only treatment option is peginterferon-alpha 180 MUg
      subcutaneously once a week for 48 weeks. CASE DESCRIPTION: A 37-year-old man with
      a Syrian background and a chronic HBV infection presented with high levels of ALT
      indicating severe hepatitis. The level of detected HBV-DNA-particles was low,
      however, indicating that the HBV infection alone could not be responsible for the
      inflammation. Further investigations revealed a superinfection with HDV. The
      patient was successfully treated with peginterferon-alpha. CONCLUSION: Severe
      hepatitis (high ALT level) in combination with a low HBV-DNA-particle level can
      indicate a HDV superinfection.

PMID- 21854666
TI  - [Menorrhagia: uterine extirpation remains the final option].
AB  - The conclusion of a recent cost-effectiveness analysis shows that hysterectomy is
      the preferred strategy in women with heavy menstrual bleeding. However, this
      conclusion is not directly applicable in general daily practice. Deciding about
      certain treatment is not only based on the best-available treatment but also on
      the experience of a physician and more importantly, on the patient's preferences.
      For heavy menstrual bleeding, it is known that patients are willing to accept a
      treatment failure rate of up to 50% in order to avoid hysterectomy. Adequate
      knowledge on the different treatment options in terms of success, effectiveness,
      and quality of life are necessary to be able to give each patient solid advice
      regarding the different treatment options. Patients' preferences were not taken
      into account in the recent cost-effectiveness analysis of the treatment of heavy
      menstrual bleeding; therefore, the results of the study are not directly
      applicable in daily practice.

PMID- 21854667
TI  - Risk factors for listeriosis in Australia.

PMID- 21854668
TI  - The effectiveness of outreach testing for hepatitis C in an immigrant Pakistani
      population.
AB  - In Scotland, an estimated 1% of the population is infected with hepatitis C virus
      (HCV). There is ethnic diversity in Scotland, with a large Pakistani sub
      population. Our aim was to investigate the prevalence of HCV in an immigrant
      Pakistani population and effectiveness of an outreach testing intervention. We
      arranged a series of HCV awareness meetings at the mosques and Pakistani Women's
      centre in the city of Dundee. Thereafter short-term outreach HCV testing clinics
      were set up in the same venues. Venous blood samples were obtained and tested for
      HCV IgG and HbsAg. A short questionnaire was also completed. In total, 177
      individuals volunteered for testing, out of an estimated 250 who attended
      meetings and a total Pakistani population in Dundee of 1723. Of those tested 170
      were Scottish Pakistanis (159 first generation, 11 second generation). There were
      145 (85.2%) men. The mean age was 45.11 (+/- S.D. 16.7) years. Seven (4.1%)
      individuals in the cohort were anti-HCV positive. Five (2.9%) were found to have
      HCV RNA by PCR. Only one patient had chronic hepatitis B infection. All patients
      with positive results were seen in the liver clinic for consideration of
      treatment. We have demonstrated that immigrant Pakistanis retain a higher
      prevalence of HCV compared to the population of their adopted country. Outreach
      targeted testing in this group can be achieved using religious and cultural
      gatherings, with only modest investment in staff time.

PMID- 21854669
TI  - Choose your menu wisely: cuisine-associated food-poisoning risks in restaurants
      in England and Wales.
AB  - The food service sector continues to be the most common setting for reported
      foodborne disease outbreaks in England and Wales. Using restaurant-associated
      foodborne outbreaks reported in England and Wales from 1992 to 2009, cuisine
      specific risk factors were examined. Of 677 restaurant outbreaks, there were 11
      795 people affected, 491 hospitalizations, and seven deaths; and Chinese, Indian,
      British and Italian cuisines were the most commonly implicated (26%, 16%, 13% and
      10%, respectively). Salmonella spp. accounted for most outbreaks of all cuisine
      types, and particularly Chinese (76%, 133/175) and Italian (55%, 38/69). Poultry
      meat was the most frequently implicated food vehicle in outbreaks associated with
      Indian (30%), Chinese (21%), and British (18%) cuisines while for Italian
      cuisine, desserts and cakes were more frequently implicated (33%). Rice dishes
      were also a common outbreak food vehicle in those restaurants serving Chinese
      (22%) and Indian (16%) cuisine. Cross-contamination was the biggest contributory
      factor associated with Chinese (46%), British (33%) and Indian (30%) cuisines
      whereas inadequate cooking (38%) and use of raw shell eggs in lightly cooked or
      uncooked food (35%) were more often associated with Italian cuisine. Over the
      surveillance period, the proportion of Salmonella Enteritidis PT4 outbreaks in
      restaurants serving Chinese cuisine significantly decreased (P<0.0001) and this
      was mirrored by an increase in S. Enteritidis non-PT4 outbreaks (P<0.0001).
      Despite this change in proportion, contributory factors such as cross
      contamination have continued to cause outbreaks throughout the 18 years. The
      results show that by stratifying the risks associated with restaurants by cuisine
      type, specific evidence of food control failures can be used to target foodborne
      illness reduction strategies.

PMID- 21854670
TI  - The poverty of the Mayan stimulus.
AB  - Poverty of the stimulus (POS) arguments have instigated considerable debate in
      the recent linguistics literature. This article uses the comparative method to
      challenge the logic of POS arguments. Rather than question the premises of POS
      arguments, the article demonstrates how POS arguments for individual languages
      lead to a reductio ad absurdum as POS arguments from genetically related
      languages are compared. Comparison leads to different contradictions for poverty
      of the negative stimulus (PONS) and poverty of the positive stimulus (POPS)
      arguments. Comparing PONS arguments leads to the conclusion that Universal
      Grammar contains language-specific versions of linguistic rules. Comparing POPS
      arguments leads to the conclusion that Universal Grammar may supply knowledge
      that is ungrammatical in the target language. The reductio shows that universal
      principles of grammar cannot be established on the basis of POS arguments from a
      single language.

PMID- 21854672
TI  - Dacryolith in an unusual case of epiphora: open or endoscopic approach?
AB  - INTRODUCTION: Dacryoliths are concretions formed in the lacrimal sac from
      cellular debris and proteins, which may calcify and cause further obstruction of
      the nasolacrimal pathway. Dacryoliths are often underlying contributors in cases
      of intermittent or chronic dacryocystitis (i.e. nasolacrimal sac inflammation,
      characterised by epiphora, pain, erythema, sac dilation and lacrimal punctum
      swelling). OBJECTIVE: We report an unusual case of dacryolith resulting in
      obstructive epiphora, managed via an endonasal endoscopic approach. METHOD: Case
      report and literature review pertaining to dacryolith. RESULTS: A 54-year-old man
      attended the multidisciplinary nasolacrimal clinic due to recurrent epiphora.
      Obstructive epiphora secondary to chronic dacryocystitis was diagnosed. He
      underwent endonasal endoscopic dacryocystorhinostomy. Intra-operatively, a large
      dacryolith was found to be the cause of epiphora. CONCLUSION: Dacryolith is an
      unusual cause of nasolacrimal duct obstruction. This case highlights this unusual
      cause, and the relevant diagnostic investigations. This case also illustrates
      successful endonasal endoscopic management, rather than an external, open
      approach.

PMID- 21854671
TI  - Biofilm formation on bone-anchored hearing aids.
AB  - OBJECTIVE: To investigate microbiological biofilm contamination of retrieved bone
      anchored hearing aids. MATERIALS AND METHODS: Nine failed, retrieved bone
      anchored hearing aids and 16 internal screws were examined by scanning electron
      microscopy. A fixture from a failing implant, which had been removed and
      disassembled under aseptic conditions, was cultured. Finally, an internal screw
      from a new, unimplanted fixture was examined by scanning electron microscopy.
      RESULTS: Debris was seen on the fixture and abutment of all bone-anchored hearing
      aids, and on the heads of the 16 internal screws. On eight screws, biofilm
      extended down the shaft to the threads, where it was several micrometres thick.
      Culture of a failing fixture yielded staphylococcus. The new, unimplanted fixture
      internal screw showed evidence of scratching and metallic debris on the threads,
      which may interfere with close fitting of the screw and subsequently facilitate
      microleakage. CONCLUSION: There may be a link between internal microbial
      contamination and failure of bone-anchored hearing aids.

PMID- 21854673
TI  - Follicular adenoma presenting as lateral aberrant thyroid.
AB  - INTRODUCTION: True benign thyroid masses very rarely present as a solitary
      lateral neck mass. Different aetiological mechanisms have been proposed for such
      masses. CASE REPORT: We report a case of thyroid follicular adenoma that
      presented as a lateral neck mass. DISCUSSION: Ectopic thyroid tissue and
      metastases from primary thyroid carcinoma should always be considered in the
      differential diagnosis of lateral neck masses. Complete investigation should
      include complete blood tests to characterise the orthotopic thyroid gland.

PMID- 21854674
TI  - Rapid Rhino versus Merocel nasal packs in septal surgery.
AB  - OBJECTIVE: To compare Rapid Rhino and Merocel packs for nasal packing after
      septoplasty, in terms of patient tolerance (both with the pack in place and
      during removal) and post-operative complications. MATERIALS AND METHODS: Thirty
      patients (aged 18-40 years) scheduled for septoplasty were included. Following
      surgery, one nasal cavity was packed with Rapid Rhino and the other one with
      Merocel. Patients were asked to record pain levels on a visual analogue score, on
      both sides, with the packs in situ and during their removal the next day. After
      pack removal, bleeding was compared on both sides. RESULTS: The mean +/- standard
      deviation pain score for the Rapid Rhino pack in situ (4.17 +/- 1.78) was less
      than that for the Merocel pack (4.73 +/- 2.05), but not significantly so (p =
      0.314). The mean pain score for Rapid Rhino pack removal (4.13 +/- 1.76) was
      significantly less that that for Merocel (6.90 +/- 1.67; p = 0.001). Bleeding
      after pack removal was significantly less for the Rapid Rhino sides compared with
      the Merocel sides (p <0.05). CONCLUSION: Rapid Rhino nasal packs are less painful
      and cause less bleeding, compared with Merocel packs, with no side effects. Thus,
      their use for nasal packing after septal surgery is recommended.

PMID- 21854675
TI  - Who benefits from reduced reproduction in parasitized hosts? An experimental test
      using the Pasteuria ramosa-Daphnia magna system.
AB  - We investigated whether parasites or hosts benefit from reduced reproduction in
      infected hosts. When parasites castrate their hosts, the regain of host
      reproduction is necessary for castration to be a host adaptation. When infecting
      Daphnia magna with Pasteuria ramosa, in a lake water based medium, 49 2% of the
      castrated females regained reproduction. We investigated the relationship between
      castration level, and parasite and host fitness proxies to determine the adaptive
      value of host castration. Hosts which regained reproduction contained less spores
      and had a higher lifetime reproduction than permanently castrated hosts. We also
      found a negative correlation between parasite and host lifetime reproduction. For
      hosts which regained reproduction we found no optimal level of castration
      associated with lifetime reproduction. These results support the view that host
      castration only is adaptive to the parasite in this system. In addition, we
      suggest that permanent castration might not be the norm under natural conditions
      in this system. Finally, we argue that a reduction in host reproduction is more
      likely to evolve as a property favouring parasites rather than hosts. To our
      knowledge this is the only experimental study to investigate the adaptive value
      of reduced host reproduction when castrated hosts can regain reproduction.

PMID- 21854677
TI  - Selenium-induced apoptosis-like cell death in Plasmodium falciparum.
AB  - Plasmodium falciparum has for some time been developing resistance against known
      anti-malarial drugs, and therefore a new drug is urgently needed. Selenium (Se),
      an essential trace element, in the form of inorganic Se, selenite (SeO32-), has
      been reported to have an anti-plasmodial effect, but its mechanism is still
      unclear. In the present study, we evaluated the anti-plasmodial effect of several
      Se compounds against P. falciparum in vitro. The anti-plasmodial effect of
      several Se compounds was analysed and their apoptosis-inducing activity was
      evaluated by morphological observation, DNA fragmentation assay and mitochondrial
      function analysis. SeO32-, methylseleninic acid, selenomethionine and
      selenocystine have anti-plasmodial effects with 50% inhibition concentration at
      9, 10, 45, and 65 MUm, respectively, while selenate and methylselenocysteine up
      to 100 MUm have no effect on parasite growth. The effective Se compounds caused
      the parasites to become shrunken and pyknotic and significantly increased
      mitochondrial damage against P. falciparum compared to the untreated control. In
      conclusion, SeO32-, methylseleninic acid, selenomethionine and selenocystine have
      anti-plasmodial activities that induce apoptosis-like cell death in P.
      falciparum, and the anti-plasmodial effects of Se seem to be based on its
      chemical forms. The apoptosis-like cell-death mechanism in P. falciparum can be
      beneficial to respond to the growing problem of drug resistance.

PMID- 21854678
TI  - A host-endoparasite network of Neotropical marine fish: are there organizational
      patterns?
AB  - Properties of ecological networks facilitate the understanding of interaction
      patterns in host-parasite systems as well as the importance of each species in
      the interaction structure of a community. The present study evaluates the network
      structure, functional role of all species and patterns of parasite co-occurrence
      in a host-parasite network to determine the organization level of a host-parasite
      system consisting of 170 taxa of gastrointestinal metazoans of 39 marine fish
      species on the coast of Brazil. The network proved to be nested and modular, with
      a low degree of connectance. Host-parasite interactions were influenced by host
      phylogeny. Randomness in parasite co-occurrence was observed in most modules and
      component communities, although species segregation patterns were also observed.
      The low degree of connectance in the network may be the cause of properties such
      as nestedness and modularity, which indicate the presence of a high number of
      peripheral species. Segregation patterns among parasite species in modules
      underscore the role of host specificity. Knowledge of ecological networks allows
      detection of keystone species for the maintenance of biodiversity and the
      conduction of further studies on the stability of networks in relation to
      frequent environmental changes.

PMID- 21854676
TI  - Genetic manipulation of schistosomes--progress with integration competent
      vectors.
AB  - Draft genome sequences for Schistosoma japonicum and S. mansoni are now
      available. The schistosome genome encodes ~13,000 protein-encoding genes for
      which the functions of few are well understood. Nonetheless, the new genes
      represent potential intervention targets, and molecular tools are being developed
      to determine their importance. Over the past 15 years, noteworthy progress has
      been achieved towards development of tools for gene manipulation and transgenesis
      of schistosomes. A brief history of genetic manipulation is presented, along with
      a review of the field with emphasis on reports of integration of transgenes into
      schistosome chromosomes.

PMID- 21854679
TI  - Olanzapine, but not aripiprazole, weight-independently elevates serum
      triglycerides and activates lipogenic gene expression in female rats.
AB  - Metabolic adverse effects such as weight gain and dyslipidaemia represent a major
      concern in treatment with several antipsychotic drugs, including olanzapine. It
      remains unclear whether such metabolic side-effects fully depend on appetite
      stimulating actions, or whether some dysmetabolic features induced by
      antipsychotics may arise through direct perturbation of metabolic pathways in
      relevant peripheral tissues. Recent clinical and preclinical studies indicate
      that dyslipidaemia could occur independently of weight gain. Using a rat model,
      we showed that subchronic treatment with olanzapine induces weight gain and
      increases adipose tissue mass in rats with free access to food. This effect was
      also observed for aripiprazole, considered metabolically neutral in the clinical
      setting. In pair-fed rats with limited food access, neither olanzapine nor
      aripiprazole induced weight gain. Interestingly, olanzapine, but not
      aripiprazole, induced weight-independent elevation of serum triglycerides,
      accompanied by up-regulation of several genes involved in lipid biosynthesis,
      both in liver and in adipose tissues. Our findings support the existence of
      tissue-specific, weight-independent direct effects of olanzapine on lipid
      metabolism.

PMID- 21854680
TI  - Acute and chronic ethanol differentially modify the emotional significance of a
      novel environment: implications for addiction.
AB  - Using open-field behaviour as an experimental paradigm, we demonstrated a complex
      interaction between the rewarding/stimulating effects and the
      anxiogenic/stressful effects of both novelty and acute or chronic amphetamine in
      mice. As a consequence of this interaction, acute amphetamine-induced
      hyperlocomotion was inhibited, whereas the expression of its sensitization was
      facilitated in a novel environment. In the present study, we aimed to investigate
      the interactions between exposure to a novel environment and the acute and
      chronic effects of ethanol (Eth), a drug of abuse known to produce anxiolytic
      like behaviour in mice. Previously habituated and non-habituated male Swiss mice
      (3 months old) were tested in an open field after receiving an acute injection of
      Eth or following repeated treatment with Eth. Acute Eth administration increased
      locomotion with a greater magnitude in mice exposed to the apparatus for the
      first time, and this was thought to be related to the attenuation of the
      stressful effects of novelty produced by the anxiolytic-like effect of acute Eth,
      leading to a subsequent prevalence of its stimulant effects. However, locomotor
      sensitization produced by repeated Eth administration was expressed only in the
      previously explored environment. This result might be related to the well-known
      tolerance of Eth-induced anxiolytic-like behaviour following repeated treatment,
      which would restore the anxiogenic effect of novelty. Our data suggest that a
      complex and plastic interaction between the emotional and motivational properties
      of novelty and drugs of abuse can critically modify the behavioural expression of
      addiction-related mechanisms.

PMID- 21854681
TI  - Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias
      for emotional information in healthy volunteers.
AB  - Individual differences in emotional processing are likely to contribute to
      vulnerability and resilience to emotional disorders such as depression and
      anxiety. Genetic variation is known to contribute to these differences but they
      remain incompletely understood. The serotonin transporter (5-HTTLPR) and alpha2B
      adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two
      separate but interacting monaminergic signalling mechanisms that have been
      implicated in both emotional processing and emotional disorders. Recent studies
      suggest that the 5-HTTLPR s allele is associated with a negative attentional bias
      and an increased risk of emotional disorders. However, such complex behavioural
      traits are likely to exhibit polygenicity, including epistasis. This study
      examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion
      polymorphisms to attentional biases for aversive information in 94 healthy male
      volunteers and found evidence of a significant epistatic effect (p<0.001).
      Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for
      aversive information was attenuated by possession of the ADRA2B deletion variant
      whereas in the absence of the s allele, the bias was enhanced. These data
      identify a cognitive mechanism linking genotype-dependent serotonergic and
      noradrenergic signalling that is likely to have implications for the development
      of cognitive markers for depression/anxiety as well as therapeutic drug effects
      and personalized approaches to treatment.

PMID- 21854682
TI  - Road to full recovery: longitudinal relationship between symptomatic remission
      and psychosocial recovery in first-episode psychosis over 7.5 years.
AB  - BACKGROUND: In recent years there has been increasing interest in functional
      recovery in the early phase of schizophrenia. Concurrently, new remission
      criteria have been proposed and several studies have examined their clinical
      relevance for prediction of functional outcome in first-episode psychosis (FEP).
      However, the longitudinal interrelationship between full functional recovery
      (FFR) and symptom remission has not yet been investigated. This study sought to:
      (1) examine the relationships between FFR and symptom remission in FEP over 7.5
      years; (2) test two different models of the interaction between both variables.
      METHOD: Altogether, 209 FEP patients treated at a specialized early psychosis
      service were assessed at baseline, 8 months, 14 months and 7.5 years to determine
      their remission of positive and negative symptoms and functional recovery.
      Multivariate logistic regression and path analysis were employed to test the
      hypothesized relationships between symptom remission and FFR. RESULTS: Remission
      of both positive and negative symptoms at 8-month follow-up predicted functional
      recovery at 14-month follow-up, but had limited value for the prediction of FFR
      at 7.5 years. Functional recovery at 14-month follow-up significantly predicted
      both FFR and remission of negative symptoms at 7.5 years, irrespective of whether
      remission criteria were simultaneously met. The association remained significant
      after controlling for baseline prognostic indicators. CONCLUSIONS: These findings
      provided support for the hypothesis that early functional and vocational recovery
      plays a pivotal role in preventing the development of chronic negative symptoms
      and disability. This underlines the need for interventions that specifically
      address early psychosocial recovery.

PMID- 21854683
TI  - Clarifying domains of internalizing psychopathology using neurophysiology.
AB  - Current initiatives such as the National Institute of Mental Health's Research
      Domain Criteria project aim to reorganize classification of mental disorders
      along neurobiological lines. Here, we describe how consideration of findings from
      psychiatric research employing two physiological measures with distinct neural
      substrates--the startle blink reflex and the error-related negativity (ERN)--can
      help to clarify relations among disorders entailing salient anxiety or depressive
      symptomatology. Specifically, findings across various studies and reviews reveal
      distinct patterns of association for both the startle blink reflex and the ERN
      with three key domains of psychopathology: (1) Fear (or phobic) disorders
      (distinguished by increased startle to unpleasant stimuli, but normal-range ERN).
      (2) Non-phobic anxiety disorders and negative affect (associated with increased
      ERN, increased startle across all types of emotional stimuli and increased
      baseline startle) and, more tentatively (3) Major depression (for which patterns
      of response for both startle and ERN appear to vary, as a function of severity
      and distinct symptomatology). Findings from this review point to distinct
      neurobiological indicators of key psychopathology domains that have been
      previously demarcated using personality and diagnostic data. Notably, these
      indicators exhibit more specificity in their relations with these three domains
      than has been seen in quantitative-dimensional models. Implications of these
      findings are discussed.

PMID- 21854684
TI  - Hypothesis-driven candidate genes for schizophrenia compared to genome-wide
      association results.
AB  - BACKGROUND: Candidate gene studies have been a key approach to the genetics of
      schizophrenia (SCZ). However, the results of these studies are confusing and no
      genes have been unequivocally implicated. The hypothesis-driven candidate gene
      literature can be appraised by comparison with the results of genome-wide
      association studies (GWAS). METHOD: We describe the characteristics of hypothesis
      driven candidate gene studies from the SZGene database, and use pathway analysis
      to compare hypothesis-driven candidate genes with GWAS results from the
      International Schizophrenia Consortium (ISC). RESULTS: SZGene contained 732
      autosomal genes evaluated in 1374 studies. These genes had poor statistical power
      to detect genetic effects typical for human diseases, assessed only 3.7% of genes
      in the genome, and had low marker densities per gene. Most genes were assessed
      once or twice (76.9%), providing minimal ability to evaluate consensus across
      studies. The ISC studies had 89% power to detect a genetic effect typical for
      common human diseases and assessed 79% of known autosomal common genetic
      variation. Pathway analyses did not reveal enrichment of smaller ISC p values in
      hypothesis-driven candidate genes, nor did a comprehensive evaluation of meta
      hypotheses driving candidate gene selection (SCZ as a disease of the synapse or
      neurodevelopment). The most studied hypothesis-driven candidate genes (COMT,
      DRD3, DRD2, HTR2A, NRG1, BDNF, DTNBP1 and SLC6A4) had no notable ISC results.
      CONCLUSIONS: We did not find support for the idea that the hypothesis-driven
      candidate genes studied in the literature are enriched for the common genetic
      variation involved in the etiology of SCZ. Larger samples are required to
      evaluate this conclusion definitively.

PMID- 21854685
TI  - Lower temperature thresholds for oviposition and egg hatching of the red palm
      weevil, Rhynchophorus ferrugineus (Coleoptera: Curculionidae), in a Mediterranean
      climate.
AB  - The red palm weevil, Rhynchophorus ferrugineus Olivier (Coleoptera:
      Curculionidae), is an economically important pest of palms worldwide. To better
      understand the phenology of R. ferrugineus populations in the Mediterranean
      basin, the objective of the present work has been to estimate the effect of
      temperatures within the range 10-25 degrees C on the reproductive parameters of
      R. ferrugineus and to determine its lower temperature thresholds for oviposition
      and egg hatching. Our results confirm that oviposition in R. ferrugineus is
      strongly affected by temperature. Lower thresholds for oviposition and egg
      hatching (15.45 degrees  and 13.95 degrees C, respectively) are below the mean
      monthly temperatures registered in winter in most of the northern shore of the
      Mediterranean basin. Under these circumstances, new palm infestations would be
      difficult during most of the winter. These results should be taken into account
      when planning some palm management practices, such as pruning or pesticide
      treatments, in areas under a Mediterranean climate.

PMID- 21854686
TI  - Polyphenol studies: time for a physiological tea party?

PMID- 21854687
TI  - Isolation and identification of an AP2/ERF factor that binds an allelic cis
      element of rice gene LRK6.
AB  - Allelic expression of the rice yield-related gene, leucine-rich receptor-like
      kinase 6 (LRK6), in the hybrid of 93-11 (Oryza sativa L. subsp. Indica var. 93
      11) and Nipponbare (O. sativa L. subsp. Japonica var. Nipponbare) is determined
      by allelic promoter cis-elements. Using deletion analysis of the LRK6 promoter,
      we identified two distinct regions that might contribute to LRK6 expression.
      Sequence alignment revealed differences in these LRK6 promoter regions in 93-11
      and Nipponbare. One of the segments, named differential sequence of LRK6 promoter
      2 (DSLP2), contains potential transcription factor binding sites. Using a yeast
      one-hybrid assay, we isolated an ethylene-responsive factor (ERF) protein that
      binds to DSLP2. Sequence analysis and a GCC-box assay showed that the ERF gene,
      O. sativa ERF 3 (OsERF3), which belongs to ERF subfamily class II, has a
      conserved ERF domain and an ERF-associated amphiphilic repression repressor
      motif. We used an in vivo mutation assay to identify a new motif (5'-TAA(A)GT-3')
      located in DSLP2, which interacts with OsERF3. These results suggest that OsERF3,
      an AP2 (APETALA 2 Gene)/ERF transcription factor, binds the LRK6 promoter at this
      new motif, which might cause differential expression of LRK6 in the 93
      11/Nipponbare hybrid.

PMID- 21854688
TI  - Searchers vs surveyors in estimating the monetary value of a QALY: resolving a
      nasty dilemma for NICE.
AB  - Recently, for many health economics researchers, empirical estimation of the
      monetary valuation of a quality-adjusted life year (QALY) has become an important
      endeavour. Different philosophical and practical approaches to this have emerged.
      On the one hand, there is a view that, with health-care budgets set centrally,
      decision-making bodies within the system can iterate, from observation of a
      series of previous decisions, towards the value of a QALY, thus searching for
      such a value. Alternatively, and more consistent with the approach taken in other
      public sectors, individual members of the public are surveyed with the aim of
      directly eliciting a preference-based - also known as a willingness-to-pay-based
      (WTP-based) - value of a QALY. While the former is based on supply-side factors
      and the latter on demand, both in fact suffer from informational deficiencies.
      Sole reliance on either would necessitate an acceptance or accommodation of
      chronic inefficiencies in health-care resource allocation. On the basis of this
      observation, this paper makes the case that in order to approach optimal decision
      making in health-care provision, a framework incorporating and thus, to a degree,
      reconciling these two approaches is to be preferred.

PMID- 21854689
TI  - Nouns and verbs in Chintang: children's usage and surrounding adult speech.
AB  - Analyzing the development of the noun-to-verb ratio in a longitudinal corpus of
      four Chintang (Sino-Tibetan) children, we find that up to about age four,
      children have a significantly higher ratio than adults. Previous cross-linguistic
      research rules out an explanation of this in terms of a universal noun bias;
      instead, a likely cause is that Chintang verb morphology is polysynthetic and
      difficult to learn. This hypothesis is supported by the fact that the development
      of Chintang children's noun-to-verb ratio correlates significantly with the
      extent to which they show a similar flexibility with verbal morphology to that of
      the surrounding adults, as measured by morphological paradigm entropy. While this
      development levels off around age three, children continue to have a higher
      overall noun-to-verb ratio than adults. A likely explanation lies in the kinds of
      activities that children are engaged in and that are almost completely separate
      from adults' activities in this culture.

PMID- 21854690
TI  - Vascular rings and slings: interesting vascular anomalies.
AB  - INTRODUCTION: A vascular ring refers to encirclement of the trachea and
      oesophagus by an abnormal combination of derivatives of the aortic arch system.
      These malformations can cause variable degrees of compression of the oesophagus,
      trachea or both. Symptoms can range from no effect to severe stridor, dyspnoea
      and/or dysphagia. METHOD AND RESULTS: This study presents a case series of six
      patients treated over a six-year period (2003-2009), illustrating the features of
      four different types of vascular ring; these types are discussed in detail. The
      clinical presentation, radiology, and microlaryngoscopy and bronchoscopy findings
      are also discussed. CONCLUSION: The management of children with vascular rings
      requires a high index of clinical suspicion to ensure prompt diagnosis. As many
      of these children present with airway symptoms, the paediatric otolaryngologist
      plays a key role in identifying and assessing their anatomical anomalies.

PMID- 21854691
TI  - Mastoiditis secondary to metastatic lung carcinoma: case report and literature
      review.
AB  - OBJECTIVE: We present a case report and systematic review of acute mastoiditis
      caused by metastatic lung cancer. CASE REPORT: A 62-year-old woman developed
      acute mastoiditis as a complication of otitis media. Cortical mastoidectomy
      revealed deposits of metastatic non-small cell lung carcinoma around the sigmoid
      sinus. The patient had previously received treatment for lung cancer, but was
      thought to be in remission. DISCUSSION: A literature review confirmed that this
      is the first reported case of mastoiditis caused by metastatic lung cancer. Only
      four similar case reports were identified: two caused by breast carcinoma, one by
      renal cell carcinoma and one by cholangiocarcinoma. Post-mortem histopathological
      studies suggest that temporal bone metastasis occurs in 22 per cent of oncology
      cases. CONCLUSION: This is the first reported case of mastoiditis caused by
      metastatic lung cancer. Metastasis to the temporal bone is not uncommon, but
      rarely causes mastoiditis.

PMID- 21854692
TI  - Aural metastasis from a nasal malignant melanoma: case report with literature
      review.
AB  - OBJECTIVE: To raise awareness of nasal malignant melanoma, a rare tumour, and to
      highlight the difficulty associated with its optimum management. METHOD: Case
      report and literature review. CASE REPORT: A 71-year-old, Caucasian man was
      diagnosed with malignant melanoma in the right nasal cavity, after presenting
      with right-sided epistaxis. He underwent endoscopic medial maxillectomy;
      histological analysis confirmed that the resection margins were clear. However,
      within six months he re-presented with a metastatic deposit of malignant melanoma
      in his right external auditory canal, for which he underwent right temporal bone
      resection. There was no evidence of distant metastasis on radiological studies.
      Unfortunately, within a month the tumour recurred in the right nasopharynx. A
      multidisciplinary team decision was made to offer the patient palliative
      chemoradiotherapy. CONCLUSION: Mucosal malignant melanoma of the nose is very
      rare, and aural metastasis from this primary site has not previously been
      reported. Optimum management must involve a multidisciplinary team.

PMID- 21854693
TI  - An anatomical study of the myelination of human laryngeal nerves.
AB  - OBJECTIVE: To determine the differences in myelination between the human
      recurrent laryngeal nerve and superior laryngeal nerve. METHODS: Fifteen
      confirmed laryngeal nerve specimens were harvested from five cadavers. Cross
      sections were examined under a photomicroscope and morphometric analysis
      performed. RESULTS: There was a significantly greater number of myelinated fibres
      than unmyelinated fibres, in both the recurrent laryngeal nerve (p = 0.018) and
      the superior laryngeal nerve (p = 0.012). There was a significantly greater
      number of myelinated fibres in the superior laryngeal nerve, compared with the
      recurrent laryngeal nerve (p = 0.028). However, there was no significant
      difference in the number of unmyelinated fibres, comparing the two nerves (p =
      0.116). CONCLUSION: These findings support those of previous studies, and provide
      further evidence against the historical plexus theory of laryngeal nerve
      morphology. The differences in the degree of myelination, both within and between
      the human laryngeal nerves, may have clinical consequence regarding recovery of
      function following nerve injury.

PMID- 21854694
TI  - Managing child and adolescent mental health problems in primary care: taking the
      leap from knowledge to practice.
AB  - In 2009, a conference at Imperial College London brought together experts on the
      primary care provision of child and adolescent mental health. The following paper
      highlights various themes from the conference, and particularly focuses on
      general practice. Despite international and national guidance, child and
      adolescent mental health provision in primary care is limited in the UK and
      globally. We argue that primary care services are in fact well placed to assess,
      diagnose, and manage child and adolescent mental health problems. The barriers to
      such provision are considered from the perspective of both service users and
      providers, and the possible ways to overcome such challenges are discussed. The
      paper is informed by various epidemiological and intervention studies and
      comparisons between different countries and health systems are explored.

PMID- 21854695
TI  - iPodTM technology for teaching patients about anticoagulation: a pilot study of
      mobile computer-assisted patient education.
AB  - AIM: To determine whether an educational strategy using a handheld, multimedia
      computer (iPodTM) is practical and sustainable for routine office-based patient
      educational tasks. BACKGROUND: With the limited amount of time allotted to the
      office encounter and the growing number of patient educational tasks, new
      strategies are needed to improve the efficiency of patient education. Education
      of patients anticoagulated with warfarin is considered critical to preventing
      complications. Despite the dangers associated with the use of warfarin,
      educational practices are variable and often haphazard. METHODS: During a four
      month period, we examined the implementation of a three-part series of iPodTM
      based patient educational modules delivered to anticoagulated patients at the
      time of routine INR (International Normalized Ratio) blood tests for outpatients
      on the anticoagulation registry at an urban community health center. FINDINGS: A
      total of 141 computer module presentations were delivered to 91 patients during
      the four-month period. In all, 44 patients on the registry had no INR checkups,
      and thus no opportunity to view the modules, and 32 patients had at least three
      INR checkups but no modules were documented. Of the 130 patients with at least
      one INR performed during the study period, 22 (16.9%) patients completed all
      three modules, 91 (70.0%) patients received at least one module, and nine (7.6%)
      patients refused to view at least one module. Neither of the two handheld
      computers was lost or stolen, and no physician time was used in this routine
      educational activity. Patients reported that the audio and visual quality was
      very good, (9.0/10); the educational experience of the patient was helpful
      (7.4/10) compared with the patient's previous warfarin education (6.3/10), and
      the computer strategy extended the INR visit duration by 1-5 min at most.
      CONCLUSIONS: The computer-assisted patient educational strategy was well received
      by patients, and uptake of the intervention by the clinic was successful and
      durable. The iPodTM strategy standardized the educational message, improved
      clinic efficiency, and helped this busy clinic meet its educational goals for
      patient education.

PMID- 21854696
TI  - The impact of funding changes on the implementation of primary health care
      policy.
AB  - AIM: To ascertain how new funding arrangements, introduced in New Zealand's 2001
      Primary Health Care (PHC) Strategy, have impacted on the expansion of nurses'
      role in general practice. BACKGROUND: Nurses are central to the new policy that
      was designed to improve the health status of New Zealanders and reduce
      inequalities in health. Nurses were to be a crucial part of the PHC team,
      expanding their current roles to provide increased access to appropriate
      services. This paper investigates how the new funding arrangements, introduced as
      part of the policy, have impacted on the expansion of nurses' roles and
      consequently the realisation of the policy goals. METHODS: Semi-structured
      interviews were undertaken with 128 key stakeholders five years after the
      introduction of the PHC Strategy, and surveys were completed by practice nurses,
      general practitioners and practice managers in purposively selected practices
      within the 20 participating Primary Health Organisations. FINDINGS: There has
      been substantial growth in the development of nursing roles for some nurses in
      general practice; however, this expansion has not been universal and one of the
      main reasons for this is the way funding devolves at the practice level. One of
      the consequences of the policymakers not taking into account the business model
      of the majority of general practices, is the resulting overarching goal of the
      strategy not being realised, and inequalities in health status remaining.

PMID- 21854697
TI  - Identifying 'at risk' women and the impact of maternal obesity on National Health
      Service maternity services.
AB  - Obesity is a public health concern worldwide, arising from multifaceted and
      complex causes that relate to individual choice and lifestyle, and the influences
      of wider society. In addition to a long-standing focus on both childhood and
      adult obesity, there has been more recent concern relating to maternal obesity.
      This review explores the published evidence relating to maternal obesity
      incidence and associated inequalities, the impact of obesity on maternity
      services, and associated guidelines. Epidemiological data comprising three
      national maternal obesity datasets within the UK have identified a significant
      increase in maternal obesity in recent years, and reflect broad socio-demographic
      inequalities particularly deprivation, ethnicity and unemployment. Obese
      pregnancies present increased risk of complications that require more resource
      intensive antenatal and perinatal care, such as caesarean deliveries, gestational
      diabetes, haemorrhage, infections and congenital anomalies. Healthcare
      professionals also face difficulties when managing the care of women in pregnancy
      as obesity is an emotive and stigmatising topic. There is a lack of good-quality
      evidence for effective interventions to tackle maternal obesity. Recently
      published national guidelines for the clinical management and weight management
      of maternal obesity offer advice for professionals, but acknowledge the
      limitations of the evidence base. The consequence of these difficulties is an
      absence of support services available for women. Further evaluative research is
      thus required to assess the effectiveness of interventions with women before,
      during and after pregnancy. Qualitative work with women will also be needed to
      help inform the development of more sensitive risk communication and women
      centred services.

PMID- 21854698
TI  - Pathogenic obesity and nutraceuticals.
AB  - Over a decade of intense research in the field of obesity has led to the
      knowledge that chronic, excessive adipose tissue expansion leads to an increase
      in the risk for CVD, type 2 diabetes mellitus and cancer. This is primarily
      thought to stem from the low-grade, systemic inflammatory response syndrome that
      characterises adipose tissue in obesity, and this itself is thought to arise from
      the complex interplay of factors including metabolic endotoxaemia, increased
      plasma NEFA, hypertrophic adipocytes and localised hypoxia. Plasma concentrations
      of vitamins and antioxidants are lower in obese individuals than in the non
      obese, which is hypothesised to negatively affect the development of inflammation
      and disease in obesity. This paper provides a review of the current literature
      investigating the potential of nutraceuticals to ameliorate the development of
      oxidative stress and inflammation in obesity, thereby limiting the onset of
      obesity complications. Research has found nutraceuticals able to positively
      modulate the activity of adipocyte cell lines and further positive effects have
      been found in other aspects of pathogenic obesity. While their ability to affect
      weight loss is still controversial, it is clear that they have a great potential
      to reverse the development of overweight and obesity-related comorbidities; this,
      however, still requires much research especially that utilising well-structured
      randomised controlled trials.

PMID- 21854699
TI  - The effects of puberty on genetic risk for disordered eating: evidence for a sex
      difference.
AB  - BACKGROUND: Differences in genetic influences on disordered eating are present
      across puberty in girls. Heritability is 0% before puberty, but over 50% during
      and after puberty. Emerging data suggest that these developmental differences may
      be due to pubertal increases in ovarian hormones. However, a critical piece of
      evidence is lacking, namely, knowledge of genetic influences on disordered eating
      across puberty in boys. Boys do not experience increases in ovarian hormones
      during puberty. Thus, if pubertal increases in genetic effects are present in
      boys, then factors in addition to ovarian hormones may drive increases in
      heritability in girls. The current study was the first to examine this
      possibility in a sample of 1006 male and female twins from the Michigan State
      University Twin Registry. METHOD: Disordered eating was assessed with the
      Minnesota Eating Behavior Survey. Pubertal development was assessed with the
      Pubertal Development Scale. RESULTS: No significant differences in genetic
      influences on disordered eating were observed in males across any developmental
      stage. Heritability was 51% in boys during pre-puberty, puberty and young
      adulthood. By contrast, in girls, genetic factors accounted for 0% of the
      variance in pre-puberty, but 51% of the variance during puberty and beyond. Sex
      differences in genetic effects were only significant during pre-puberty, as the
      best-fitting models constrained heritability to be equal across all males,
      pubertal females and young adult females. CONCLUSIONS: The results highlight sex
      specific effects of puberty on genetic risk for disordered eating and provide
      indirect evidence of a role for ovarian hormones and/or other female-specific
      factors.

PMID- 21854701
TI  - A neuronally based model of contrast gain adaptation in fly motion vision.
AB  - Motion-sensitive neurons in the visual systems of many species, including humans,
      exhibit a depression of motion responses immediately after being exposed to
      rapidly moving images. This motion adaptation has been extensively studied in
      flies, but a neuronal mechanism that explains the most prominent component of
      adaptation, which occurs regardless of the direction of motion of the visual
      stimulus, has yet to be proposed. We identify a neuronal mechanism, namely
      frequency-dependent synaptic depression, which explains a number of the features
      of adaptation in mammalian motion-sensitive neurons and use it to model fly
      motion adaptation. While synaptic depression has been studied mainly in spiking
      cells, we use the same principles to develop a simple model for depression in a
      graded synapse. By incorporating this synaptic model into a neuronally based
      model for elementary motion detection, along with the implementation of a center
      surround spatial band-pass filtering stage that mimics the interactions among a
      subset of visual neurons, we show that we can predict with remarkable success
      most of the qualitative features of adaptation observed in electrophysiological
      experiments. Our results support the idea that diverse species share common
      computational principles for processing visual motion and suggest that such
      principles could be neuronally implemented in very similar ways.

PMID- 21854702
TI  - Risk maps for the presence and absence of Phlebotomus perniciosus in an endemic
      area of leishmaniasis in southern Spain: implications for the control of the
      disease.
AB  - The aim of this study was to construct risk maps for the presence of the dominant
      Leishmania infantum vector, P. perniciosus, and check its usefulness (a) to
      predict the risk of canine leishmaniasis and (b) to define effective
      leishmaniasis control measures. We obtained data for the presence/absence of P.
      perniciosus at 167 sampling sites in southern Spain, from which we also took a
      series of ecological and climate-related data. The probability of P. perniciosus
      presence was estimated as a function of these environmental variables and
      generated spatial risk maps. Altitude, land use and drainage hole features (with
      or without PVC piping) were retained as the only predictors for the distribution
      of this vector species. Drainage hole features in retaining walls, with or
      without PVC piping, produce significant variations in the probability of P.
      perniciosus presence, varying from 2.3 to 91.8% if PVC piping is absent and from
      0.4 to 66.5% if all holes have PVC piping. It was concluded that the use of PVC
      piping in drainage holes could help to reduce leishmaniasis transmission.

PMID- 21854700
TI  - Attention bias toward threat is associated with exaggerated fear expression and
      impaired extinction in PTSD.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) develops in a minority of
      traumatized individuals. Attention biases to threat and abnormalities in fear
      learning and extinction are processes likely to play a critical role in the
      creation and/or maintenance of PTSD symptomatology. However, the relationship
      between these processes has not been established, particularly in highly
      traumatized populations; understanding their interaction can help inform neural
      network models and treatments for PTSD. METHOD: Attention biases were measured
      using a dot probe task modified for use with our population; task stimuli
      included photographs of angry facial expressions, which are emotionally salient
      threat signals. A fear-potentiated startle paradigm was employed to measure
      atypical physiological response during acquisition and extinction phases of fear
      learning. These measures were administered to a sample of 64 minority (largely
      African American), highly traumatized individuals with and without PTSD. RESULTS:
      Participants with PTSD demonstrated attention biases toward threat; this
      attentional style was associated with exaggerated startle response during fear
      learning and early and middle phases of extinction, even after accounting for the
      effects of trauma exposure. CONCLUSIONS: Our findings indicate that an
      attentional bias toward threat is associated with abnormalities in 'fear load' in
      PTSD, providing seminal evidence for an interaction between these two processes.
      Future research combining these behavioral and psychophysiological techniques
      with neuroimaging will be useful toward addressing how one process may modulate
      the other and understanding whether these phenomena are manifestations of
      dysfunction within a shared neural network. Ultimately, this may serve to inform
      PTSD treatments specifically designed to correct these atypical processes.

PMID- 21854703
TI  - Delta-aminolevulinate dehydratase activity in red blood cells of rats infected
      with Trypanosoma evansi.
AB  - The aim of this study was to evaluate the activity of delta-aminolevulinate
      dehydratase (delta-ALA-D) in red blood cells of rats infected with Trypanosoma
      evansi and establish its association with haematocrit, serum levels of iron and
      zinc and lipid peroxidation. Thirty-six male rats (Wistar) were divided into 2
      groups with 18 animals each. Group A was non-infected while Group B was
      intraperitoneally infected, receiving 7.5*106 trypomastigotes per animal. Each
      group was divided into 3 subgroups of 6 rats and blood was collected during
      different periods post-infection (p.i.) as follows: day 5 (A1 and B1), day 15 (A2
      and B2) and day 30 PI (A3 and B3). Blood samples were collected by cardiac
      puncture to estimate red blood cell parameters (RBC), delta-ALA-D activity and
      serum levels of iron, zinc and thiobarbituric acid reactive substances (TBARS).
      Rats in group B showed a significant (P<0.05) reduction of RBC count, haemoglobin
      concentration and haematocrit at days 5 and 15 p.i. The activity of delta-ALA-D
      in blood was significantly (P<0.001) increased at days 15 and 30 p.i. delta-ALA-D
      activity in blood had a significant (P<0.05) negative correlation with
      haematocrit (r=-0.61) and haemoglobin (r=-0.70) at day 15 p.i. There was a
      significant (P<0.05) decrease in serum iron and zinc levels and an increase in
      TBARS levels (P<0.05) during infection. The delta-ALA-D activity in blood was
      negatively correlated with the levels of iron (r=-0.68) and zinc (r=-0.57) on day
      30 p.i. It was concluded that the increased activity of delta-ALA-D in blood
      might have occurred in response to the anaemia in remission as heme synthesis was
      enhanced.

PMID- 21854706
TI  - Editorial - immunotherapy for prostate cancer.

PMID- 21854704
TI  - Role of dog behaviour and environmental fecal contamination in transmission of
      Echinococcus multilocularis in Tibetan communities.
AB  - On the Eastern Tibetan Plateau region (Sichuan province, China) dogs are regarded
      as important definitive hosts of Echinococcus multilocularis. We studied dog
      spatial behaviour in 4 Tibetan villages in order to determine the role of dogs in
      environmental contamination and their potential interactions with small mammal
      intermediate hosts. We identified definitive host species and Echinococcus spp.
      infection status of feces collected in the field by PCR methods and analysed the
      spatial distribution of canid feces. Nocturnal space utilization of GPS collared
      dogs in and around villages was also undertaken. E. multilocularis DNA was
      amplified in 23% of dog feces (n=142) and in 15% of fox feces (n=13) but this
      difference was not significant. However, dog feces were more frequently observed
      (78% of collected feces) than fox feces and are therefore assumed to largely
      contribute to human environment contamination. Feces were mainly distributed
      around houses of dog owners (0-200 m) where collared dogs spent the majority of
      their time. Inside villages, the contamination was aggregated in some micro-foci
      where groups of dogs defecated preferentially. Finally, small mammal densities
      increased from the dog core areas to grasslands at the periphery of villages
      occasionally used by dogs; male dogs moving significantly farther than females.
      This study constitutes a first attempt to quantify in a spatially explicit way
      the role of dogs in E. multilocularis peri-domestic cycles and to identify
      behavioural parameters required to model E. multilocularis transmission in this
      region.

PMID- 21854707
TI  - Legends in urology.

PMID- 21854708
TI  - New treatment options for castrate-resistant prostate cancer: a urology
      perspective.
AB  - INTRODUCTION: Castrate-resistant prostate cancer (CRPC) is the most clinically
      advanced form of prostate cancer. Prior to 2004, treatment options for patients
      with CRPC were limited to palliative care with mitoxantrone. However, two phase
      III trials in 2004 showed improved survival with docetaxel compared with
      mitoxantrone in patients with metastatic CRPC. Docetaxel remains the current
      standard chemotherapy for CRPC. MATERIALS AND METHODS: A literature review was
      conducted to ascertain agents recently approved or in development for CRPC as
      well as several treatment algorithms being developed in this patient population.
      RESULTS: Recently, the US Food and Drug Administration (FDA) approved
      chemotherapy agents including cabazitaxel, a novel taxane, for the treatment of
      patients with metastatic CRPC who were previously treated with docetaxel-based
      chemotherapy. The immunotherapy sipuleucel-T and the androgen biosynthesis
      inhibitor, abiraterone, have also just been approved. A number of other novel
      agents are in clinical development for the management of CRPC. CONCLUSIONS:
      Options for the management of CRPC are rapidly expanding. Based on improved
      survival with docetaxel in patients with CRPC, chemotherapy is being investigated
      for use earlier in the prostate cancer disease spectrum. Studies are actively
      evaluating chemotherapy in the neoadjuvant and adjuvant settings for patients
      with high risk, localized prostate cancer. A multidisciplinary approach towards
      patients with difficult-to-manage prostate cancer in which urologists familiarize
      themselves with these newer systemic agents and refer appropriate patients to
      oncologists may be beneficial.

PMID- 21854709
TI  - An overview on preclinical and clinical experiences with photodynamic therapy for
      bladder cancer.
AB  - Photodynamic therapy (PDT) is one of the most interesting methods of photo
      treatment. In general, PDT is a modality for the treatment of non-muscle invasive
      tumors. PDT is very well suited in managing bladder cancer, as the bladder is
      accessible by endoscopy and the tumors are most often limited to the mucosa or
      sub-mucosa. PDT is likely more useful for patients with recurrent tumors after
      conventional therapies, as well as for patients with diffuse non-muscle invasive
      bladder carcinomas that are refractory to standard treatments before the
      commitment to radical extirpative surgery, particularly in patients at surgical
      high risk. The treatment of tumors with PDT includes three major parameters:
      presence of oxygen in tumor tissue, administration of a photosensitizer, and
      subsequent exposure to light. The PDT mechanism relies on the in situ generation
      of cytotoxic agents by the activation of a light-sensitive drug, resulting in
      cell death. In this review, we present past and current advances in the use of
      PDT with urinary bladder cancer and discuss the future roles for this type of
      therapy in the treatment of bladder cancer.

PMID- 21854710
TI  - Injection of botulinum toxin type A in the urethral sphincter to treat lower
      urinary tract dysfunction: review of indications, techniques and results: 2011
      update.
AB  - INTRODUCTION: The first application of botulinum toxin type A (BoNT-A) in urology
      was its injection into the urinary sphincter to treat neurogenic detrusor
      sphincter dyssynergia (DSD) in quadriplegic men. Since that first report by
      Dyskatra et al in 1988, the results of focal BTA injections into the sphincter,
      the bladder wall and lately into the prostate have raised the interest of the
      urology community in this promising new therapeutic modality. This is an evidence
      based review of the current indications, techniques and outcomes of BTA
      injections into the urethral sphincter. MATERIALS AND METHODS: The Medline
      database was searched for the period between 1966 and October 2010, using the
      keywords 'botulinum toxin' and 'urethra' or 'urethral sphincter'. English written
      articles ere selected. A level of evidence according to the Oxford Centre for
      evidence-based medicine was assigned to each article. CONCLUSION: Since our first
      review in 2006, very little has been added to the literature on the use of
      botulinum toxin injected into the external sphincter. At present, those most
      likely to benefit from intrasphincteric BTA injection are MS patients suffering
      the symptoms of DSD and quadriplegic men with DSD unable to perform self
      catheterization. Well developed and conducted studies are necessary; these must
      be done urgently to better define the place and the results of this drug
      otherwise widely used in other indications in urology.

PMID- 21854711
TI  - Short term urgency outcomes following transobturator midurethral sling placement.
AB  - INTRODUCTION: Research suggests that midurethral sling placement may have a
      beneficial effect on urgency (U) and urge incontinence (UUI). This study examined
      short term U/UUI outcomes in patients undergoing TVT-O placement. METHODS: One
      hundred patients undergoing TVT-O placement were prospectively assessed using 3
      day bladder diary, combined with multiple validated incontinence questionnaires
      focusing on UUI, U and QoL. RESULTS: At 6 week assessment, improvements in daily
      pad use (2.6 to 0.9) and incontinence episodes (3.6 to 0.7) were seen (p < 0.05,
      both comparisons). Eighty-two patients reported cure of stress incontinence.
      Focused outcome scores for UUI improved from 2.0 (+/- 1.1) to 0.8 (+/- 1.0) (p
      value < 0.001), with 39% and 29% of patients reporting score resolution and
      improvement, respectively. Similarly, mean Urinary Perception Score improved from
      10.1 (+/- 4.4) to 5.8 (+/- 3.7) (p value < 0.001) with cure/improvement
      identified in 75%. Eighty-four patients did not require anticholinergics
      postoperatively. Interestingly, patients reporting residual SUI but improved UUI
      demonstrated QoL scores only slightly worse than patients with SUI cure and
      improved or persistent UUI. CONCLUSION: TVT-O placement is associated with
      cure/improvement in a significant proportion of patients. In addition,
      significant improvement in QoL is seen following TVT-O placement.

PMID- 21854712
TI  - Cross validation of the prostate cancer radiotherapy late toxicity (PCRT)
      questionnaire with the expanded prostate cancer index composite (EPIC)
      instrument.
AB  - INTRODUCTION: A 29-item prostate cancer radiotherapy (PCRT) questionnaire with
      genitourinary (GU), gastrointestinal (GI), and sexual (S) domains has been
      previously validated for the assessment of late toxicity health-related quality
      of life (HRQoL) effects. The study objective was to cross-validate the PCRT
      domains versus the expanded prostate cancer index composite (EPIC) questionnaire
      urinary (U), bowel (B), hormonal (H), and S subscales. METHODS AND MATERIALS: A
      single-institution cross-sectional PCRT patient cohort was surveyed. Descriptive
      and intra- and inter-class correlation coefficient statistics for the various
      EPIC and PCRT HRQoL domain scores were generated. Univariable and multivariable
      Cox and logistic regressions were performed depending on the HRQoL endpoint being
      assessed. RESULTS: A total of 189/276 patients (68%) completed questionnaires
      with EPIC and PCRT missing data rates of 9% and 4%, respectively. Mean age was
      75.8 years (SD 5.5) and the mean time of questionnaire completion after
      radiotherapy was 852 days (range 212-1454 days). Mean EPIC urinary (85.1 SD
      12.9), bowel (84.1 SD 15.8), sexual (21.8 SD 20.7), and hormonal (85.3 SD 13.7)
      as well as PCRT genitourinary (66.1 SD 15.3), gastrointestinal (83.6 SD 14.3),
      and sexual (39.4 SD 21.6) domain scores were calculated. Intraclass correlation
      coefficients comparing corresponding EPIC/PCRT domains ranged from 0.50-0.88.
      Interclass correlation coefficients for non-corresponding EPIC/PCRT domains
      ranged from 0.16-0.43 and 0.23-0.30, respectively. EPIC B/U, PCRT GI/GU and PCRT
      S required arcsin square root transformation and EPIC S/H domains required
      dichotomous transformations prior to univariable/multivariable analyses.
      Multivariable analysis demonstrated novel associations between predictive
      variables and HRQoL domains including between the PTV-bladder overlap volume and
      PCRT GU score. CONCLUSIONS: The PCRT is a compact, valid, and HRQoL instrument
      with very high questionnaire compliance rates and similar statistical properties
      to the EPIC instrument. However, dichotomization of the PRCT S data was not
      required which suggests some potential statistical advantage to the PCRT.

PMID- 21854713
TI  - Urinary continence after radical prostatectomy: the patient perspective.
AB  - INTRODUCTION: To compare the commonly used 0-1 pad definition of urinary
      continence for postoperative functional outcome after radical prostatectomy and
      the correlation with self-reported urinary continence and to determine whether a
      patient questionnaire can deliver more accurate continence status rates. MATERIAL
      AND METHODS: We evaluated a cohort of 873 men who underwent radical prostatectomy
      (RP) at the General Hospital in Vienna between 1998 and 2006. Patients were
      surveyed with a questionnaire regarding their postoperative outcome and
      postoperative urinary incontinence. Baseline and pathological factors were
      examined to determine whether or not they had an impact on the continence status.
      RESULTS AND LIMITATIONS: A total of 65.2% of men (n = 337) reported themselves to
      be continent, in contrast 85.1% were continent if the pad definition was applied.
      Of those using no pads, 93.4% considered themselves continent, while 24.5% of
      patients using one pad/day did. Overall, 86.5%, 9.8% and 3.7% of continent
      patients regained continence within 6 months, 6 to 12 months and after 1 year of
      RP, respectively. A total of 71.5% of men under 65 years old reported full
      urinary continence, while only 57.0% of men older than 65 considered themselves
      continent. Men < 65 years recovered full urinary control significantly faster
      than men older than 65 years- 3.6 versus 4.7 months. Neurovascular bundle
      resection has a negative effect on continence. CONCLUSIONS: The ultimate
      continence status should be measured with self-administered disease specific
      questionnaires at 24 months after RP, as it differs from standard physician
      reported methods. Age and neurovascular bundle resection are variables affecting
      continence. We believe that patients' subjective reports of their continence are
      crucial and that multiple outcomes should be objectively measured. Therefore we
      suggest that validated questionnaires dealing with the patients' perspective
      postoperatively should be included in routine follow up.

PMID- 21854715
TI  - Chronic prostatitis and small intestinal bacterial overgrowth: effect of
      rifaximin.
AB  - INTRODUCTION: This pilot study determined the efficacy of rifaximin, a gut
      directed antibiotic, in reducing chronic prostatitis (CP) and gastrointestinal
      (GI) symptoms in patients with CP type III. The prevalence of small intestinal
      bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS) in patients with
      CP was also evaluated. MATERIALS AND METHODS: Chronic prostatitis patients were
      recruited and screened for SIBO and IBS using the lactulose breath test (LBT) and
      Rome II criteria, respectively. Patients with a positive LBT result and Chronic
      Prostatitis Symptom Index (CPSI) score >= 15 received rifaximin 550 mg three
      times daily for 10 days. The CPSI score and global improvement of CP and GI
      symptoms were ascertained at screening (ie, 7 days before therapy), at baseline
      immediately before therapy (ie, day 0), and on days 14 and 28. RESULTS: Fourteen
      of 16 CP patients (88%) had a positive LBT result and were included in this
      therapeutic study (mean age, 41 years). Mean CPSI score significantly decreased
      from screening to day 28 (ie, 18 days after rifaximin treatment; p = 0.043). Mean
      abdominal pain and bloating scores were also significantly reduced on day 28
      versus baseline (p = 0.010 and p = 0.003, respectively). Chronic prostatitis
      patients with IBS and SIBO had a statistically significant response as well.
      CONCLUSION: Data from this pilot study suggest that SIBO and IBS are common in CP
      and that patients with CP and SIBO may benefit from rifaximin therapy. Further
      studies are warranted.

PMID- 21854716
TI  - Intra-tumor Doppler flow patterns do not predict malignancy of renal masses in a
      United States population.
AB  - INTRODUCTION: Increased use of nephron sparing surgery has revealed a small but
      significant percentage of benign tumors. Improved imaging techniques have aided
      in diagnosis, but are still unable to differentiate benign from malignant tumors.
      We sought to evaluate whether the intra-tumor Doppler flow pattern could predict
      the presence of renal cell cancer (RCC). MATERIALS AND METHODS: Standard
      grayscale ultrasound (US) and Power Doppler ultrasound (PDUS) were performed on
      40 patients referred to our clinic for suspicious renal masses diagnosed by CT or
      MRI from December 2007 to May 2010. PDUS findings were used to classify tumors
      according to vascular patterns as proposed by Jinzaki et al, where pattern 0, 1,
      or 2 are considered diagnostic of benign renal lesions while patterns 3 and 4
      predict malignancy. Clinical and pathological data were reviewed; ultrasound
      findings were correlated with histopathology. RESULTS: Of the 40 patients
      included for analysis, 13 underwent active surveillance, 24 underwent partial or
      radical nephrectomy, and 3 underwent ablative procedures. Twenty-seven (67.5%)
      patients had pathological specimens available for review, of which 22 patients
      had RCC and 5 had benign pathology. Intra-observer (kappa 0.46-0.70) and inter
      observer (kappa 0.41-0.56) reliability were reasonable, but ratings didn't
      correlate with pathologic outcomes (all kappa < 0). CONCLUSIONS: Our results
      suggest that PDUS may not be helpful in the diagnosis of malignant renal masses
      detected by CT or MRI. Further studies are needed to elucidate a preoperative
      tool useful in diagnosing malignancy in renal masses.

PMID- 21854714
TI  - Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro
      study of sunitinib and pazopanib in renal cell carcinoma cell lines.
AB  - OBJECTIVES: We examined the in vitro cellular effects of the multi-targeted
      receptor tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib on a series of
      human renal cell carcinoma (RCC) cell lines. METHODS: The human RCC cell lines
      769-P, 786-O, HRC-24, HRC-31, HRC-45, HRC-78, SK-26B, and SK-45 were treated with
      varying concentrations of sunitinib and pazopanib. Cellular proliferation and
      cellular death were assessed using the CellTiter-Blue Cell Viability Assay and
      the TUNEL assay, respectively. Effective doses (ED) for inhibition of cellular
      proliferation or induction of apoptosis were calculated for sunitinib and
      pazopanib in each RCC cell line. RESULTS: Both sunitinib and pazopanib exhibited
      anti-proliferative activity to varying degree against all human RCC cell lines;
      however, sunitinib's effects were achieved at significantly lower concentrations.
      Moreover, sunitinib had a direct pro-apoptotic effect on all tested cell lines,
      while pazopanib failed to induce apoptosis in any of the examined human RCC cell
      lines even at maximal concentrations. CONCLUSIONS: Although sunitinib and
      pazopanib are often used interchangeably in the clinical setting, our results
      suggest that in-vitro biological activity of the two agents differs. Sunitinib
      exhibits a cytotoxic effect on RCC cell lines, while pazopanib's activity is
      solely cytostatic. These data may be clinically relevant given the current lack
      of comparative in-vivo studies between the two agents.

PMID- 21854717
TI  - Thermal injury causing delayed perforation of small bowel after transurethral
      resection of bladder tumor without evidence of bladder perforation.
AB  - Risk of thermal injury to the bowel when utilizing electrocautery at the bladder
      dome has been reported anecdotally. This is a case report of a 64-year-old man
      with urothelial carcinoma in situ of the bladder who underwent transurethral
      resection of bladder tumor at the posterior bladder wall near the dome without
      evidence of perforation. The postoperative course was complicated by delayed
      small bowel perforation likely secondary to transmission of thermal energy during
      fulguration of the resection bed. This injury highlights the need for particular
      prudence when resecting and fulgurating bladder tumors using monopolar
      electrocautery, specifically in the regions adjacent to bowel.

PMID- 21854718
TI  - HDR monotherapy for man with radiotherapy contraindications and prostate cancer.
AB  - There is debate about the optimal management of high risk localized prostate
      cancer. Initial options include surgery or radiation combined with androgen
      deprivation therapy. We describe a case of a patient with contraindications to
      radiotherapy who was managed with high dose rate (HDR) brachytherapy as his sole
      treatment. A medically operable patient presented with a T2c N0 M0 Gleason 9
      adenocarcinoma with an initial PSA of 19.9 ng/mL. Previously, he had severe
      ulcerative colitis managed with pancolectomy and a neorectum fashioned from ileum
      anastomosed behind his prostate. After a negative extended lymph node dissection,
      a HDR brachytherapy implant of 35 Gy in 5 fractions over 3 days was delivered. No
      androgen deprivation therapy was used. The treatment was extremely well tolerated
      in the short and long term with no significant bowel or bladder side effects
      observed in follow up. After 7 years, his PSA was 0.04 ng/mL. The excellent long
      term biochemical control and minimal radiation toxicity observed in this patient
      suggests that HDR monotherapy may be a safe and effective alternative for high
      risk prostate cancer patients in whom EBRT is contraindicated.

PMID- 21854719
TI  - Transrectal implantation of electromagnetic transponders following radical
      prostatectomy for delivery of IMRT.
AB  - Surgical treatment for men with localized prostate cancer -open, laparoscopic, or
      robotically-assisted-- remains one of the therapeutic mainstays for this group of
      patients. Despite the stage migration witnessed in patients with prostate cancer
      since the introduction of prostate-specific antigen (PSA) screening, detection of
      extraprostatic disease at the time of surgery and biochemical recurrence
      following prostatectomy pose significant therapeutic challenges. Radiation
      therapy (RT) after radical prostatectomy (RP) has been associated with a survival
      benefit in both the adjuvant and salvage setting. Nevertheless, optimal targeting
      of the prostate bed following surgery remains challenging. The Calypso 4D
      Localization System (Calypso Medical Technologies, Seattle, WA, USA) is a target
      positioning device that continuously monitors the location of three implantable
      electromagnetic transponders. These transponders can be placed into the empty
      prostatic bed after prostatectomy to facilitate the delivery of radiation therapy
      in the post-surgical setting. In this article, we detail our technique for
      transrectal placement of electromagnetic transponders into the post-prostatectomy
      bed for the delivery of adjuvant or salvage intensity-modulated radiation
      therapy. We prefer this technique of post-surgical radiation therapy because it
      allows for improved localization of the target area allowing for the maximal
      delivery of the radiation dose while minimizing exposure of surrounding normal
      tissues. Although emerging, our initial oncologic and functional outcomes have
      been promising.

PMID- 21854720
TI  - Open clinical uro-oncology trials in Canada.

PMID- 21854721
TI  - Inadvertent cryoablation of exophytic upper tract urothelial carcinoma without
      pelvicalyceal involvement.
AB  - Ablative therapy has recently emerged as an option for the treatment of small
      renal masses (SRMs). Benign tumors and indolent renal cell carcinoma (RCC)
      represent a majority of these masses, although an additional but often
      unappreciated consideration is upper tract urothelial carcinoma (UC). We report
      the case of a 74-year-old man with upper tract UC presenting as a SRM without any
      apparent involvement of the pelvicalyceal system, leading to its inadvertent
      cryoablation. We also discuss the role of renal biopsy in the management of SRMs
      undergoing an ablative procedure.

PMID- 21854722
TI  - [Primary immunodeficiencies: An emerging challenge in developing countries].

PMID- 21854723
TI  - [Chronic cough in pediatrics: Review and analysis].
AB  - OBJECTIVE: To review and to analyze the existing literature regarding chronic
      cough in children. MATERIAL AND METHODS: We searched published articles in PubMed
      using the key words: cough, chronic cough, chronic cough in children, persistent
      cough, gastroesophageal reflux in children. RESULTS: Cough in children is common;
      the majority of cases reflect respiratory infections. Cough is rarely associated
      to a serious disorder. All children with cough persisting for more than 8 weeks
      should be evaluated. A careful history, physical examination, chest x-ray, and
      spirometry (in an able child) are recommended for all children with chronic
      cough. If a diagnosis is no evident (nonspecific cough), then an approach based
      on characterizing the cough as "wet" or "dry" is helpful. In each case, specific
      etiology-based treatment is recommended when possible; otherwise, a therapeutic
      trial is indicated with inhaled corticosteroids (ICS) for children with dry cough
      (for possible asthma) and antibiotics for wet cough (for possible protracted
      bacterial bronchitis [PPB] or sinusitis). The treatment should be reviewed within
      the specified time frame for normal response. If no effect is obvious, the
      treatment should be stopped and alternative diagnosis considered. Multiple
      etiologies may need to be treated concomitantly. Every effort should be made to
      identify the underlying cause. Data suggests potential harmful effects of
      medications used for symptomatic relief of acute or chronic cough in children.
      CONCLUSIONS: Medical history and physical examination, together with appropriate
      investigations allow the correct diagnosis of chronic cough. The diagnostic
      approach is summarized in Figures 1 and 2. Most cases can be managed with this
      algorithm. For the difficult, complex and rare cases referral to a Pediatric
      specialist in Allergy, Clinical Immunology and Respiratory Diseases is warranted.

PMID- 21854724
TI  - [Asthma prevalence in adolescents. Relation to sex and active smoking].
AB  - BACKGROUND: Asthma prevalence in adolescents appears to be increasing and
      determinants are not well established. OBJECTIVE: To determine the association
      between sex and active smoking with asthma prevalence in adolescents.
      PARTICIPANTS AND METHOD: In this cross-sectional study 6,922 students, ages 12 to
      18 years, residents in an area of northeastern Mexico, were included. We
      developed a questionnaire based on The International Study of Asthma and
      Allergies in Childhood (ISAAC) and on The European Community Respiratory Health
      Survey (ECRHS). The association between sex and active smoking with asthma
      prevalence was determined using a logistic regression model. RESULTS: Of the
      total population, 46.3% were males, 7.3% suffered from asthma and 17.3% were
      cigarette smokers. We found that sex (OR = 0.55; CI 95%: 0.48-0.63) and active
      smoking (adjusted OR = 1.12; CI 95%: 0.89-1.42) were not associated with asthma
      prevalence. Females (OR = 1.44; CI 95%: 1.13-1.84) and active smoking (adjusted
      OR = 1.38; CI 95%: 1.15-1.67) were associated with prevalence of wheezing in the
      last 12 months, and with prevalence of dry cough at night (OR = 1.53; CI 95%:
      1.34-1.76). CONCLUSIONS: Teenager males and active smoking were not associated
      with asthma prevalence. Females had an association with wheezing in the last 12
      months and dry cough at night.

PMID- 21854725
TI  - [Prevalence of hypersensitivity to Cupressus pollen in allergic patients in
      Monterey, Mexico].
AB  - BACKGROUND: Cupressus pollen is one of the main causes of allergic respiratory
      disease in North America. In a previous study of pollen concentration in
      Monterrey, Cupressus occupied the 3rd place in frequency. OBJECTIVE: To know the
      sensitization to Cupressus in patients treated at our center. METHODS: We
      conducted an observational, cross-sectional and prospective study, with a
      questionnaire to assess potential exposure and allergic symptoms to pollen, skin
      tests with allergen extract of Cupressus 1:20 dilution, and skin tests with
      others 36 aeroallergens in our hospital. RESULTS: We did Cupressus skin test in
      256 patients (136 women), 130 younger than 18 years old and 126 adults. The skin
      test was positive in 39 patients (15.2%). Of the 36 aeroallergens tested,
      Cupressus occupied the 7th place in frequency. Of the 130 under 18 years, only 10
      (7.7%) had a positive skin test. Among the other 129 adults, 29 (22.5%) had a
      positive skin test (p = 0.001). Patients with a positive skin test Cupressus had
      at least one positive skin test to other aeroallergen in 97% of cases (p =
      0.001). CONCLUSIONS: Cupressus sensitization in our study group was high (15.2%).
      The routine use of allergen extract of Cupressus should be considered in patients
      with respiratory allergy. However, it is necessary to determine precisely the
      prevalence of sensitization and its possible clinical implications.

PMID- 21854726
TI  - [An overview of primary immunodeficiency in Mexico].
AB  - Primary immunodeficiencies are rare immunologic diseases whose main
      characteristics are recurrent infections. These diseases are frequently
      unsuspected and the delayed diagnosis makes complications irreversible with the
      consequent poor quality of life. In Mexico, primary immunodeficiencies have a low
      prevalence, which is secondary to under-diagnosis and the lack of specialized
      laboratory studies in most hospitals. Since there is a registration of primary
      immunodeficiency cases in Europe and other developed countries, it is possible to
      estimate the incidence of primary immunodeficiencies and to elaborate guidelines
      of diagnosis and treatment. In our country we do not have any epidemiological
      registry; however, from 1998 to 2004 the number of cases of primary
      immunodeficiency has increased; the minimal incidence calculated is 0.16 to 0.24
      per 100,000 births for chronic granulomatous disease, severe combined
      immunodeficiency and X linked agammaglobulinemia, this data is still very low
      compared to other international registries. We present an epidemiological review
      of primary immunodeficiency prevalence in Mexico compared to some international
      reports.

PMID- 21854727
TI  - [Satisfactory evolution of a patient diagnosed in childhood with Bruton's
      disease].
AB  - Bruton's agammaglobulinemia is a primary immunodeficiency with a disease onset
      during the first months of age, when the maternal serum immunoglobulin levels
      decrease. It is characterized by recurrent infections and agammaglobulinemia. We
      report the case of a 6-year-old male patient with third-degree consanguinity,
      product of a third pregnancy and complete immunization scheme. He had a history
      of oral candidiasis at the age of 3 months, chicken pox at the age of 7 months,
      and two episodes of complicated bronchopneumonia at the age of 1 year and 6
      years. He was admitted to the hospital because of fever and cough. Examination of
      the chest showed rales and right basilar hypoventilation, and a blood cell count
      revealed leukocytosis and neutrophilia. The diagnosis of pneumonia was made. He
      was treated with IV antibiotics. Serum immunoglobulins were reported to be low
      (IgM 55 mg/dL, IgA 0.9 mg/dL, and IgG 199 mg/dL). With these findings the
      clinical diagnosis of X-linked agammaglobulinemia (ALX) was concluded. A
      molecular test was performed fining a BTK gene confirming the diagnosis of
      Bruton's disease. Therapy with intravenous IgG was started every 21 days. During
      his evolution, he presented three episodes of rhinosinusitis, one of suppurative
      otitis media, and four events of pneumonia that required 37 days of
      hospitalization. After hospital discharge, the patient was free of infections and
      he returned to his daily activities. In cases of recurrent and severe respiratory
      infections in children, we must consider primary immunodeficiency disease in the
      differential diagnosis, mainly antibiotic deficiency. Early diagnosis and
      treatment improves the survival and quality of life in these patients.

PMID- 21854728
TI  - [Wiskott-Aldrich syndrome].
AB  - The Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by
      congenital microthrombocytopenia, eczema and recurrent infections. This paper
      reports the case of a 3-year-6-month male patient, whose maternal uncle died at
      the age of 3 months due to fulminant sepsis from a pulmonary infection. The
      patient was a product of the first pregnancy, he was born at 27 weeks' gestation
      and weighed 1,400 g. As a neonate he was hospitalized during the first 2 months
      of life because of a low gastrointestinal bleeding, thrombocytopenia and severe
      infections. In the next 4 months and before coming to our hospital the infant was
      hospitalized 54 times. On admission he presented disseminated dermatosis,
      enlarged neck lymph nodes and psychomotor retardation. Laboratory studies
      revealed hemoglobin 8.1 g/dL, platelets 31,000/uL, mean platelet volume 5.6 fL,
      IgM 39.3 mg/dL, IgA 67 mg/dL, IgG 1,380 mg/dL. On several occasions he received
      globular packages and platelet concentrates. The infusion of immunoglobulin G was
      started every 21 days. Bone marrow transplantation was delayed due to the
      complications that merited 13 hospitalizations and severe thrombocytopenia, low
      gastrointestinal bleeding, septic arthritis, infectious gastroenteritis, chronic
      suppurative otitis media and severe folliculitis. At the age of 4 years BMT of
      cord was performed, and 26 days after transplantation he presented septic shock
      and died. The prognosis of bone marrow transplantation in Wiskott-Aldrich
      syndrome and in other primary immunodeficiencies depends on the promptness of its
      performance at early stages in life. It is important that the first contact
      physicians be aware of the primary immunodeficiency signs and symptoms.

PMID- 21854729
TI  - [Severe congenital neutropenia].
AB  - Severe congenital neutropenia is a primary immunodeficiency; the lack of
      maturation of neutrophil precursor in bone marrow and severe neutropenia are the
      subjacent characteristics which explain a marked susceptibility to severe and
      recurrent infections; bacteria and fungi are the most common etiologic agents. We
      report the case of an infant with severe congenital neutropenia that began at 4
      days from birth with perianal abscess infections, sepsis, liver abscess,
      gingivitis and oral ulcers; she required multiple hospitalizations because of the
      severity of the infections. Isolated agents were Pseudomonas aeruginosa,
      Staphylococcus hominis and Klebsiella sp. The bone marrow examination showed
      maturation arrest of myeloid forms, thus confirming the diagnosis of severe
      congenital neutropenia. Granulocyte colony-stimulating factor was started. The
      severe congenital neutropenia should be considered in patients with neutropenia
      and infections in the first month of life. Early diagnosis and treatment improve
      survival and quality of life of these patients.

PMID- 21854731
TI  - Mobile phone technology identifies and recruits trained citizens to perform CPR
      on out-of-hospital cardiac arrest victims prior to ambulance arrival.
AB  - AIM: In a two-parted study, evaluate a new concept were mobile phone technology
      is used to dispatch lay responders to nearby out-of-hospital cardiac arrests
      (OHCAs). METHODS: Mobile phone positioning systems (MPS) can geographically
      locate selected mobile phone users at any given moment. A mobile phone service
      using MPS was developed and named Mobile Life Saver (MLS). Simulation study: 25
      volunteers named mobile responders (MRs) were connected to MLS. Ambulance time
      intervals from 22 consecutive OHCAs in 2005 were used as controls. The MRs
      randomly moved in Stockholm city centre and were dispatched to simulated OHCAs
      (identical to controls) if they were within a 350 m distance. Real life study:
      during 25 weeks 1271-1801 MRs trained in CPR were connected to MLS. MLS was
      activated at the dispatch centre in parallel with ambulance dispatch when an OHCA
      was suspected. The MRs were dispatched if they were within 500 m from the
      suspected OHCA. RESULTS: Simulation study: mean response time for the MRs
      compared to historical ambulance time intervals was reduced by 2 min 20s (44%),
      p<0.001, (95% CI, 1 min 5s - 3 min 35s). The MRs reached the simulated OHCA prior
      to the historical control in 72% of cases. Real life study: the MLS was triggered
      92 times. In 45% of all suspected and in 56% of all true OHCAs the MRs arrived
      prior to ambulance. CPR was performed by MRs in 17% of all true OHCAs and in 30%
      of all true OHCAs if MRs arrived prior to ambulance. CONCLUSION: Mobile phone
      technology can be used to identify and recruit nearby CPR-trained citizens to
      OHCAs for bystander CPR prior to ambulance arrival.

PMID- 21854730
TI  - Autophagy suppresses age-dependent ischemia and reperfusion injury in livers of
      mice.
AB  - BACKGROUND & AIMS: As life expectancy increases, there are greater numbers of
      patients with liver diseases who require surgery or transplantation. Livers of
      older patients have significantly less reparative capacity following ischemia and
      reperfusion (I/R) injury, which occurs during these operations. There are no
      strategies to reduce the age-dependent I/R injury. We investigated the role of
      autophagy in the age dependence of sensitivity to I/R injury. METHODS:
      Hepatocytes and livers from 3- and 26-month-old mice were subjected to in vitro
      and in vivo I/R, respectively. We analyzed changes in autophagy-related proteins
      (Atg). Mitochondrial dysfunction was visualized using confocal and intravital
      multi-photon microscopy of isolated hepatocytes and livers from anesthetized
      mice, respectively. RESULTS: Immunoblot, autophagic flux, genetic, and imaging
      analyses all associated the increase in sensitivity to I/R injury with age with
      decreased autophagy and subsequent mitochondrial dysfunction due to calpain
      mediated loss of Atg4B. Overexpression of either Atg4B or Beclin-1 recovered
      Atg4B, increased autophagy, blocked the onset of the mitochondrial permeability
      transition, and suppressed cell death after I/R in old hepatocytes.
      Coimmunoprecipitation analysis of hepatocytes and Atg3-knockout cells showed an
      interaction between Beclin-1 and Atg3, a protein required for autophagosome
      formation. Intravital multi-photon imaging revealed that overexpression of Beclin
      1 or Atg4B attenuated autophagic defects and mitochondrial dysfunction in livers
      of older mice after I/R. CONCLUSIONS: Loss of Atg4B in livers of old mice
      increases their sensitivity to I/R injury. Increasing autophagy might ameliorate
      liver damage and restore mitochondrial function after I/R.

PMID- 21854732
TI  - Successful therapeutic hypothermia for cardiac arrest in a patient with a left
      ventricular assist device.

PMID- 21854733
TI  - Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The
      association with therapeutic hypothermia.
AB  - AIM: To study the systemic levels of matrix metalloproteinases (MMP) -7, -8 and 
      9 and their inhibitor TIMP-1 in cardiac arrest patients and the association with
      mild therapeutic hypothermia treatment on the serum concentration of these
      enzymes. METHODS: MMP-7, -8 and -9 and tissue inhibitor of metalloproteinases-1
      (TIMP-1) were analysed in blood samples obtained from 51 patients resuscitated
      from cardiac arrest. The samples were taken at 24 and 48 h from restoration of
      spontaneous circulation (ROSC). The biomarker levels were compared between
      patients (N=51) and healthy controls (N=10) and between patients who did (N=30)
      and patients who did not (N=21) receive mild therapeutic hypothermia. RESULTS:
      MMP-7 (median 0.47 ng/ml), MMP-8 (median 31.16 ng/ml) and MMP-9 (median 253.00
      ng/ml) levels were elevated and TIMP-1 levels suppressed (median 78.50 ng/ml) in
      cardiac arrest patients as compared with healthy controls at 24h from ROSC.
      Hypothermia treatment associated with attenuated elevation of MMP-9 (p=0.001) but
      not MMP-8 (p=0.02) or MMP-7 (p=0.69). Concentrations of MMPs -7, -8 and -9
      correlated with the leukocyte count but not with C-reactive protein (CRP) or
      neurone-specific enolase (NSE) levels. CONCLUSION: We demonstrated that the
      systemic levels of MMP-7, -8 and -9 but not TIMP-1 are elevated in cardiac arrest
      patients in the 48 h post-resuscitation period relative to the healthy controls.
      Patients who received therapeutic hypothermia had lower MMP-9 levels compared to
      non-hypothermia treated patients, which generates hypothesis about attenuation of
      inflammatory response by hypothermia treatment.

PMID- 21854734
TI  - Clinically plausible hyperventilation does not exert adverse hemodynamic effects
      during CPR but markedly reduces end-tidal PCO2.
AB  - AIMS: Ventilation at high respiratory rates is considered detrimental during CPR
      because it may increase intrathoracic pressure limiting venous return and forward
      blood flow generation. We examined whether ventilation at high, yet clinically
      plausible, tidal volumes could also be detrimental, and further examined effects
      on end-tidal pCO(2) (P(ET)CO(2)). METHODS: Sixteen domestic pigs were randomized
      to one of four ventilatory patterns representing two levels of respiratory rate
      (min(-1)) and two levels of tidal volume (ml/kg); i.e., 10/6, 10/18, 33/6, and
      33/18 during chest compression after 8 min of untreated VF. RESULTS: Data (mmHg,
      mean +/- SD) are presented in the order listed above. Ventilation at 33/18
      prompted higher airway pressures (p<0.05) and persistent expiratory airway flow
      (p<0.05) before breath delivery demonstrating air trapping. The right atrial
      pressure during chest decompression showed a statistically insignificant increase
      with increasing minute-volume (7 +/- 4, 10+/-3, 12 +/- 1, and 13 +/- 3; p=0.055);
      however, neither the coronary perfusion pressure (23 +/- 1, 17 +/- 6, 18 +/- 6,
      and 21 +/- 2; NS) nor the cerebral perfusion pressure (32 +/- 3, 23 +/- 8, 30 +/-
      12, and 31 +/- 3; NS) was statistically different. Yet, increasing minute-volume
      reduced the P(ET)CO(2) demonstrating a high dependency on tidal volumes delivered
      at currently recommended respiratory rates. CONCLUSIONS: Increasing respiratory
      rate and tidal volume up to a minute-volume 10-fold higher than currently
      recommended had no adverse hemodynamic effects during CPR but reduced P(ET)CO(2)
      suggesting that ventilation at controlled rate and volume could enhance the
      precision with which P(ET)CO(2) reflects CPR quality, predicts return of
      circulation, and serve to guide optimization of resuscitation interventions.

PMID- 21854735
TI  - Increasing frequency of opioid prescriptions for chronic abdominal pain in US
      outpatient clinics.
AB  - BACKGROUND & AIMS: Opioids are sometimes used to treat chronic abdominal pain.
      However, opioid analgesics have not been proven to be an effective treatment for
      chronic abdominal pain and have been associated with drug misuse, constipation,
      and worsening abdominal pain. We sought to estimate the national prescribing
      trends and factors associated with opioid prescribing for chronic abdominal pain.
      METHODS: Chronic abdominal pain-related visits by adults to US outpatient clinics
      were identified using reason-for-visit codes from the National Ambulatory Medical
      Care Survey and National Hospital Ambulatory Medical Care Survey (1997-2008).
      Data were weighted to produce national estimates of opioid prescriptions over
      time. Logistic regression analyses, adjusted for complex survey design, were
      performed to identify factors associated with opioid use. RESULTS: The number of
      outpatient visits for chronic abdominal pain consistently decreased over time
      from 14.8 million visits (95% confidence interval [CI], 11.6-18.0 visits) in 1997
      through 1999 to 12.2 million visits (95% CI, 9.0-15.6 visits) or 1863 visits per
      100,000 population in 2006 through 2008 (P for trend = 0.04). Conversely, the
      adjusted prevalence of visits for which an opioid was prescribed increased from
      5.9% (95% CI, 3.5%-8.3%) in 1997 through 1999 to 12.2% (95% CI, 7.5%-17.0%) in
      2006 through 2008 (P = 0.03 for trend). Opioid prescriptions were most common
      among patients aged 25 to 40 years old (odds ratio [OR] 4.6; 95% CI, 1.2-18.4).
      Opioid prescriptions were less common among uninsured (OR 0.1; 95% CI, 0.04-0.40)
      and African American (OR 0.3; 95% CI, 0.1-0.9) patients. CONCLUSIONS: From 1997
      to 2008 opioid prescriptions for chronic abdominal pain more than doubled.
      Further studies are needed to better understand the reasons for and consequences
      of this trend.

PMID- 21854736
TI  - High-resolution manometry studies are frequently imperfect but usually still
      interpretable.
AB  - BACKGROUND & AIMS: Clinical esophageal manometry can be technically challenging.
      We investigated the prevalence and causes of technically imperfect, high
      resolution esophageal pressure topography (EPT) studies at a tertiary referral
      hospital. METHODS: We reviewed 2000 consecutive clinical EPT studies that had
      been performed with consistent technique and protocol. A study was considered
      technically imperfect if there was a problem with pressure signal acquisition, if
      the catheter did not pass through the esophagogastric junction (EGJ), or if there
      were fewer than 7 evaluable swallows (without double-swallowing, and so forth).
      Data from the technically imperfect studies were interpreted blindly to determine
      a diagnosis; this diagnosis was compared with the diagnosis based on chart
      review. RESULTS: We identified 414 technically imperfect studies (21% of the
      series). These were attributed to fewer than 7 evaluable swallows (58%),
      inability to traverse the EGJ (29%), sensor or thermal compensation malfunction
      (7%), and miscellaneous artifacts (6%). The most frequent causes of failure to
      traverse the EGJ were a large hiatal hernia (50%) and achalasia (24%). The
      condition most frequently associated with an incomplete swallow protocol was
      achalasia (33%). Despite the limitations, the diagnosis of achalasia was achieved
      correctly by blinded interpretation in 77% of cases and nonblinded interpretation
      in 94% of cases. CONCLUSIONS: Technically imperfect EPT studies are common in a
      tertiary care center; large hiatal hernia and achalasia were the most frequent
      causes. However, despite the technical limitations, the data still could be
      interpreted, especially in the context of associated endoscopic and radiographic
      data.

PMID- 21854737
TI  - Giardiasis confined to the terminal ileum.

PMID- 21854738
TI  - Development and validation of the irritable bowel syndrome satisfaction with care
      scale.
AB  - BACKGROUND & AIMS: Satisfaction with care is an important measure of quality,
      from the patients' perspective, and could also affect outcomes. However, there is
      no standard measure of patient satisfaction for irritable bowel syndrome (IBS)
      care; a multi-item, condition-specific instrument is needed. METHODS: Using
      standard qualitative methods, we conducted focus groups to identify items that
      patients associated with satisfaction in their care for IBS. These and additional
      items identified by experts were placed into a preliminary questionnaire, which
      was refined through pilot testing and cognitive debriefing by additional
      patients, as well as standard statistical methods. The resulting instrument and
      several external validation measures were administered to 300 adult US patients
      with IBS. Factor analysis was performed to identify clinically relevant subscales
      and then psychometric properties were assessed. RESULTS: We developed an IBS
      satisfaction with care scale (IBS-SAT) that has 38 items from 5 clinically
      relevant subscales (connection with provider, education, benefits of visit,
      office attributes, and access to care). This IBS-SAT had a high level of internal
      consistency (Crohnbach's alpha = .96). Convergent validity was established by
      correlations between the IBS-SAT and a single, global satisfaction with care
      question (r = 0.68; P < .001), and a generic, multi-item satisfaction scale
      (physician satisfaction questionnaire-18) (r = 0.75, P < .001). Discriminant
      validity (among known groups) was established across groups that were stratified
      based on IBS-quality of life (r = 0.34; P < .0001), IBS severity (functional
      bowel disorders severity index) (r = -0.21; P < .001), and number of unmet
      expectations (r = -0.38; P < .0001). CONCLUSIONS: The IBS-SAT is a validated
      measure of patient satisfaction with IBS care. As a new, condition-specific
      instrument, it is likely to be a useful tool for quality measurement, health
      services research, and clinical trials.

PMID- 21854739
TI  - CNS hypoxia is more pronounced in murine cerebral than noncerebral malaria and is
      reversed by erythropoietin.
AB  - Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and
      development of adjunct therapies is hampered by limited knowledge of its
      pathogenesis. To assess the role of cerebral hypoxia, we used two experimental
      models of CM, Plasmodium berghei ANKA in CBA and C57BL/6 mice, and two models of
      malaria without neurologic signs, P. berghei K173 in CBA mice and P. berghei ANKA
      in BALB/c mice. Hypoxia was demonstrated in brain sections using intravenous
      pimonidazole and staining with hypoxia-inducible factor-1alpha-specific antibody.
      Cytopathic hypoxia was studied using poly (ADP-ribose) polymerase-1 (PARP-1) gene
      knockout mice. The effect of erythropoietin, an oxygen-sensitive cytokine that
      mediates protection against CM, on cerebral hypoxia was studied in C57BL/6 mice.
      Numerous hypoxic foci of neurons and glial cells were observed in mice with CM.
      Substantially fewer and smaller foci were observed in mice without CM, and
      hypoxia seemed to be confined to neuronal cell somas. PARP-1-deficient mice were
      not protected against CM, which argues against a role for cytopathic hypoxia.
      Erythropoietin therapy reversed the development of CM and substantially reduced
      the degree of neural hypoxia. These findings demonstrate cerebral hypoxia in
      malaria, strongly associated with cerebral dysfunction and a possible target for
      adjunctive therapy.

PMID- 21854740
TI  - Aquaporin-1 promotes angiogenesis, fibrosis, and portal hypertension through
      mechanisms dependent on osmotically sensitive microRNAs.
AB  - Changes in hepatic vasculature accompany fibrogenesis, and targeting angiogenic
      molecules often attenuates fibrosis in animals. Aquaporin-1 (AQP1) is a water
      channel, overexpressed in cirrhosis, that promotes angiogenesis by enhancing
      endothelial invasion. The effect of AQP1 on fibrogenesis in vivo and the
      mechanisms driving AQP1 expression during cirrhosis remain unclear. The purpose
      of this study was to test the effect of AQP1 deletion in cirrhosis and explore
      mechanisms regulating AQP1. After bile duct ligation, wild-type mice overexpress
      AQP1 that colocalizes with vascular markers and sites of robust angiogenesis.
      AQP1 knockout mice demonstrated reduced angiogenesis compared with wild-type
      mice, as evidenced by immunostaining and endothelial invasion/proliferation in
      vitro. Fibrosis and portal hypertension were attenuated based on immunostaining,
      portal pressure, and spleen/body weight ratio. AQP1 protein, but not mRNA, was
      induced by hyperosmolality in vitro, suggesting post-transcriptional regulation.
      Endothelial cells from normal or cirrhotic mice were screened for microRNA (miR)
      expression using an array and a quantitative PCR. miR-666 and miR-708 targeted
      AQP1 mRNA and were decreased in cirrhosis and in cells exposed to
      hyperosmolality, suggesting that these miRs mediate osmolar changes via AQP1.
      Binding of the miRs to the untranslated region of AQP1 was assessed using
      luciferase assays. In conclusion, AQP1 promotes angiogenesis, fibrosis, and
      portal hypertension after bile duct ligation and is regulated by osmotically
      sensitive miRs.

PMID- 21854741
TI  - Increased expression of peripheral blood leukocyte genes implicate CD14+ tissue
      macrophages in cellular intestine allograft rejection.
AB  - Recurrent rejection shortens graft survival after intestinal transplantation
      (ITx) in children, most of whom also experience early acute cellular rejection
      (rejectors). To elucidate mechanisms common to early and recurrent rejection, we
      used a test cohort of 20 recipients to test the hypothesis that candidate
      peripheral blood leukocyte genes that trigger rejection episodes would be evident
      late after ITx during quiescent periods in genome-wide gene expression analysis
      and would achieve quantitative real-time PCR replication pre-ITx (another
      quiescent period) and in the early post-ITx period during first rejection
      episodes. Eight genes were significantly up-regulated among rejectors in the late
      post-ITx and pre-ITx periods, compared with nonrejectors: TBX21, CCL5, GNLY,
      SLAMF7, TGFBR3, NKG7, SYNE1, and GK5. Only CCL5 was also up-regulated in the
      early post-ITx period. Among resting peripheral blood leukocyte subsets in
      randomly sampled nonrejectors, CD14(+) monocytes expressed the CCL5 protein
      maximally. Compared with nonrejectors, rejectors demonstrated higher counts of
      both circulating CCL5(+)CD14(+) monocytes and intragraft CD14(+) monocyte-derived
      macrophages in immunohistochemistry of postperfusion and early post-ITx biopsies
      from the test and an independent replication cohort. Donor-specific
      alloreactivity measured with CD154(+) T-cytotoxic memory cells correlated with
      the CCL5 gene and intragraft CD14(+) monocyte-derived macrophages at graft
      reperfusion and early post-ITx. CCL5 gene up-regulation and CD14(+) macrophages
      likely prime cellular ITx rejection. Infiltration of reperfused intestine
      allografts with CD14(+) macrophages may predict rejection events.

PMID- 21854742
TI  - A mouse mammary tumor virus env-like exogenous sequence is strictly related to
      progression of human sporadic breast carcinoma.
AB  - A viral etiology of human breast cancer (HBC) has been postulated for decades
      since the identification of mouse mammary tumor virus (MMTV). The detection of
      MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs
      increased attention to this hypothesis. Looking for MMTVels during cancer
      progression may contribute to a better understanding of their role in HBC.
      Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples
      were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal
      hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in
      situ (DCISs), 20 infiltrating ductal carcinomas (IDCs), and 26 normal epithelial
      cells collateral to a DCIS or an IDC. Controls included reductive mammoplastic
      tissue, thyroid and colon carcinoma, and blood samples from healthy donors.
      MMTVels were detected by fluorescence-nested PCR. DNA samples from the tissues of
      nine patients were analyzed by real-time quantitative PCR, revealing a different
      viral load correlated with stage of progression. Furthermore, as never previously
      described, the presence of MMTVels was investigated by chromogenic in situ
      hybridization. MMTVels were found in 19% of normal epithelial cells collateral to
      a DCIS or an IDC, 27% of ADHs, 82% of DCISs, and 35% of IDCs. No MMTVels were
      found in the control samples. Quantitative PCR and chromogenic in situ
      hybridization confirmed these results. These data could contribute to our
      understanding of the role of MMTVels in HBC.

PMID- 21854743
TI  - A3 adenosine receptor agonist reduces brain ischemic injury and inhibits
      inflammatory cell migration in rats.
AB  - A3 adenosine receptor (A3AR) is recognized as a novel therapeutic target for
      ischemic injury; however, the mechanism underlying anti-ischemic protection by
      the A3AR agonist remains unclear. Here, we report that 2-chloro-N(6)-(3
      iodobenzyl)-5'-N-methylcarbamoyl-4'-thioadenosine (LJ529), a selective A3AR
      agonist, reduces inflammatory responses that may contribute to ischemic cerebral
      injury. Postischemic treatment with LJ529 markedly reduced cerebral ischemic
      injury caused by 1.5-hour middle cerebral artery occlusion, followed by 24-hour
      reperfusion in rats. This effect was abolished by the simultaneous administration
      of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. LJ529
      prevented the infiltration/migration of microglia and monocytes occurring after
      middle cerebral artery occlusion and reperfusion, and also after injection of
      lipopolysaccharides into the corpus callosum. The reduced migration of microglia
      by LJ529 could be related with direct inhibition of chemotaxis and down
      regulation of spatiotemporal expression of Rho GTPases (including Rac, Cdc42, and
      Rho), rather than by biologically relevant inhibition of inflammatory
      cytokine/chemokine release (eg, IL-1beta, TNF-alpha, and MCP-1) or by direct
      inhibition of excitotoxicity/oxidative stress (not affected by LJ529). The
      present findings indicate that postischemic activation of A3AR and the resultant
      reduction of inflammatory response should provide a promising therapeutic
      strategy for the treatment of ischemic stroke.

PMID- 21854744
TI  - Modeling oculopharyngeal muscular dystrophy in myotube cultures reveals reduced
      accumulation of soluble mutant PABPN1 protein.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease caused
      by an alanine tract expansion mutation in poly(A) binding protein nuclear 1
      (expPABPN1). To model OPMD in a myogenic and physiological context, we generated
      mouse myoblast cell clones stably expressing either human wild type (WT) or
      expPABPN1 at low levels. Transgene expression is induced on myotube
      differentiation and results in formation of insoluble nuclear PABPN1 aggregates
      that are similar to those observed in patients with OPMD. Quantitative analysis
      of PABPN1 in myotube cultures revealed that expPABPN1 accumulation and
      aggregation is greater than that of the WT protein. We found that aggregation of
      expPABPN1 is more affected than WT PABPN1 by inhibition of proteasome activity.
      Consistent with this, in myotube cultures expressing expPABPN1, deregulation of
      the proteasome was identified as the most significantly perturbed pathway.
      Differences in the accumulation of soluble WT and expPABPN1 were consistent with
      differences in ubiquitination and rate of protein turnover. This study
      demonstrates, for the first time to our knowledge, that, in myotubes, the ratio
      of soluble/insoluble expPABPN1 is significantly lower compared with that of the
      WT protein. We suggest that this difference can contribute to muscle weakness in
      OPMD.

PMID- 21854745
TI  - Protein signatures for classification and prognosis of gastric cancer a signaling
      pathway-based approach.
AB  - Current methods have limited accuracy in predicting survival and stratifying
      patients with gastric cancer for appropriate treatment. We sought to identify
      protein signatures of gastric cancer for classification and prognostication. The
      Protein Pathway Array (initial study) and Western blot (confirmation) were used
      to assess the protein expression in a total of 199 fresh frozen gastric samples.
      There were 56 paired samples divided into a training set (n = 37) and a
      validation set (n = 19) for the identification of differentially expressed
      proteins between tumor and normal tissues. There were 56 tumor samples used to
      identify proteins correlating with tumor and nodal staging. All 93 tumor samples
      were used to identify candidate proteins for predicting survival. We confirmed
      the survival prediction of the candidate proteins by using an additional cohort
      of gastric cancer samples (n = 50). There were 22 proteins differentially
      expressed between normal and tumor tissues. Nine proteins were selected to build
      the predictor to classify normal and tumor samples. Ten proteins were
      differentially expressed among different T stages and four of these were
      associated with invasive behavior. An additional four proteins were associated
      with lymph node metastasis. Two proteins were identified as independent risk
      factors for overall survival. This study indicated that some dysregulated
      signaling proteins could be selected as useful biomarkers for tumor
      classification and predicting outcome in gastric cancer patients.

PMID- 21854746
TI  - Periostin is induced in glomerular injury and expressed de novo in interstitial
      renal fibrosis.
AB  - Matricellular proteins participate in the pathogenesis of chronic kidney
      diseases. We analyzed glomerular gene expression profiles from patients with
      proteinuric diseases to identify matricellular proteins contributing to the
      progression of human nephropathies. Several genes encoding matricellular
      proteins, such as SPARC, THBS1, and CTGF, were induced in progressive
      nephropathies, but not in nonprogressive minimal-change disease. Periostin showed
      the highest induction, and its transcript levels correlated negatively with
      glomerular filtration rate in both glomerular and tubulointerstitial specimen. In
      well-preserved renal tissue, periostin localized to the glomerular tuft, the
      vascular pole, and along Bowman's capsule; no signal was detected in the
      tubulointerstitial compartment. Biopsies from patients with glomerulopathies and
      renal dysfunction showed enhanced periostin expression in the mesangium, tubular
      interstitium, and sites of fibrosis. Periostin staining correlated negatively
      with renal function. alpha-smooth muscle actin-positive mesangial and
      interstitial cells localized close to periostin-positive sites, as indicated by
      co-immunofluorescence. In vitro stimulation of mesangial cells by external
      addition of TGF-beta1 resulted in robust induction of periostin. Addition of
      periostin to mesangial cells induced cell proliferation and decreased the number
      of cells expressing activated caspase-3, a marker of apoptosis. These human data
      indicate for the first time a role of periostin in glomerular and interstitial
      injury in acquired nephropathies.

PMID- 21854747
TI  - Twist1 is up-regulated in gastric cancer-associated fibroblasts with poor
      clinical outcomes.
AB  - Stromal fibroblasts perform important roles in cancer development and
      progression. Overexpression of Twist1, a basic helix-loop-helix transcription
      factor, is often associated with aggressive behavior in many tumors. In this
      study, we investigated Twist1 expression patterns in gastric stromal fibroblasts
      and cancer cells using a monoclonal Twist1 antibody after validating the
      effectiveness of four commercial Twist1-specific antibodies. Twist1 expression
      was more frequently observed in gastric cancer-associated fibroblasts (CAFs) than
      in other cancer cells but was otherwise rarely expressed in noncancerous tissue.
      In laser capture microdissection of stromal fibroblasts, Twist1 immunopositive
      fibroblasts exhibited significantly increased Twist1, fibroblast-specific protein
      1, and CXCL14 mRNA expression. Furthermore, Twist1 mRNA expression showed a
      significant linear correlation with that of platelet-derived growth factor
      receptors beta and alpha. We found that conditioned media from Twist1-expressing
      skin and lung fibroblasts significantly promote invasion of gastric cancer cells
      in vitro. In 195 gastric cancer samples, CAF Twist1 expression was associated
      with tumor size, invasion depth, and lymph node metastasis. Twist1 was also
      associated with poor prognosis in patients with gastric cancer, particularly in
      those with the diffuse type. In conclusion, CAFs in gastric cancer frequently
      have altered Twist1 expression, and increased Twist1 expression in fibroblasts
      contributes to the progression of cancer cells and poor patient survival.

PMID- 21854748
TI  - Distinct developmental requirements for isolated lymphoid follicle formation in
      the small and large intestine: RANKL is essential only in the small intestine.
AB  - Cryptopatches (CPs) and isolated lymphoid follicles (ILFs) are organized
      intestinal lymphoid tissues that develop postnatally in mice and include stromal
      cells expressing the receptor activator of nuclear factor kappa-B ligand (RANKL).
      We investigated how stromal RANKL influences the development and differentiation
      of CPs and ILFs by analyzing the development of these lymphoid structures in
      knockout mice lacking RANKL. We found that RANKL(-/-) mice had a fourfold
      reduction in the overall density of CPs in the small intestine compared to
      control mice, with the largest decrease in the proximal small intestine. No B
      cells were present in CPs from the small intestine of RANKL(-/-) mice and ILF
      formation was completely blocked. In sharp contrast, colonic ILFs containing B
      cells were present in RANKL(-/-) mice. Stromal cells within CPs in the small
      intestine of RANKL(-/-) mice did not express CXCL13 (originally called B
      lymphocyte chemoattractant) and often lacked other normally expressed stromal
      cell antigens, whereas colonic lymphoid aggregates in RANKL(-/-) mice retained
      stromal CXCL13 expression. The CXCL13-dependent maturation of precursor CPs into
      ILFs is differentially regulated in the small intestine and colon, with an
      absolute requirement for RANKL only in the small intestine.

PMID- 21854749
TI  - Homozygous and heterozygous p53 knockout rats develop metastasizing sarcomas with
      high frequency.
AB  - The TP53 tumor suppressor gene is mutated in the majority of human cancers.
      Inactivation of p53 in a variety of animal models results in early-onset
      tumorigenesis, reflecting the importance of p53 as a gatekeeper tumor suppressor.
      We generated a mutant Tp53 allele in the rat using a target-selected mutagenesis
      approach. Here, we report that homozygosity for this allele results in complete
      loss of p53 function. Homozygous mutant rats predominantly develop sarcomas with
      an onset of 4 months of age with a high occurrence of pulmonary metastases.
      Heterozygous rats develop sarcomas starting at 8 months of age. Molecular
      analysis revealed that these tumors exhibit a loss-of-heterozygosity of the wild
      type Tp53 allele. These unique features make this rat highly complementary to
      other rodent p53 knockout models and a versatile tool for investigating
      tumorigenesis processes as well as genotoxic studies.

PMID- 21854750
TI  - Epac1-mediated, high glucose-induced renal proximal tubular cells hypertrophy via
      the Akt/p21 pathway.
AB  - The mechanisms involved in tubular hypertrophy in diabetic nephropathy are
      unclear. We investigated the role of exchange protein activated by cAMP 1(Epac1),
      which activates Rap-family G proteins in cellular hypertrophy. Epac1 is expressed
      in heart, renal tubules, and in the HK-2 cell line. In diabetic mice, increased
      Epac1 expression was observed, and under high glucose ambience (HGA), HK-2 cells
      also exhibited increased Epac1 expression. We isolated a 1614-bp DNA fragment
      upstream of the initiation codon of Epac1 gene, inclusive of glucose response
      elements (GREs). HK-2 or COS7 cells transfected with the Epac1 promoter revealed
      a dose-dependent increase in its activity under HGA. Mutations in GRE motifs
      resulted in decreased promoter activity. HK-2 cells exhibited a hypertrophic
      response and increased protein synthesis under HGA, which was reduced by Epac1
      siRNA or -mutants, whereas the use of a protein kinase A inhibitor had minimal
      effect. Epac1 transfection led to cellular hypertrophy and increased protein
      synthesis, which was accentuated by HGA. HGA increased the proportion of cells in
      the G0/G1 cell-cycle phase, and the expression of pAkt and the cyclin-dependent
      kinase inhibitors p21 and p27 was increased while the activity of cyclin
      dependent kinase 4 decreased. These effects were reversed following transfection
      of cells with Epac1-siRNA or -mutants. These data suggest that HGA increases GRE
      dependent Epac1 transcription, leading to cell cycle arrest and instigation of
      cellular hypertrophy.

PMID- 21854751
TI  - Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse
      model of tauopathy and in human Alzheimer's disease brain.
AB  - Neurofibrillary tangles (NFT), intracellular inclusions of abnormal fibrillar
      forms of microtubule associated protein tau, accumulate in Alzheimer's disease
      (AD) and other tauopathies and are believed to cause neuronal dysfunction, but
      the mechanism of tau-mediated toxicity are uncertain. Tau overexpression in cell
      culture impairs localization and trafficking of organelles. Here we tested the
      hypothesis that, in the intact brain, changes in mitochondrial distribution occur
      secondary to pathological changes in tau. Array tomography, a high-resolution
      imaging technique, was used to examine mitochondria in the reversible transgenic
      (rTg)4510, a regulatable transgenic, mouse model and AD brain tissue.
      Mitochondrial distribution is progressively disrupted with age in rTg4510 brain,
      particularly in somata and neurites containing Alz50-positive tau aggregates.
      Suppression of soluble tau expression with doxycycline resulted in complete
      recovery of mitochondrial distribution, despite the continued presence of
      aggregated tau. The effect on mitochondrial distribution occurs without
      concomitant alterations in neuropil mitochondrial size, as assessed by both array
      tomography and electron microscopy. Similar mitochondrial localization
      alterations were also observed in human AD tissue in Alz50+ neurons, confirming
      the relevance of tau to mitochondrial trafficking observed in this animal model.
      Because abnormalities reverted to normal if soluble tau was suppressed in rTg4510
      mice, even in the continued presence of fibrillar tau inclusions, we suggest that
      soluble tau plays an important role in mitochondrial abnormalities, which likely
      contribute to neuronal dysfunction in AD.

PMID- 21854752
TI  - Kupffer cells influence parenchymal invasion and phenotypic orientation, but not
      the proliferation, of liver progenitor cells in a murine model of liver injury.
AB  - Activation of myofibroblasts (MF) and extracellular matrix (ECM) deposition
      predispose the expansion and differentiation of liver progenitor cells (LPC)
      during chronic liver injury. Because Kupffer cells (KC) are active modulators of
      tissue response and fibrosis, we analyzed their role in a model of LPC
      proliferation. A choline-deficient diet, supplemented by ethionine (CDE) was
      administrated to C57Bl/6J mice that were depleted of KC by repeated injections of
      clodronate (CLO) and compared to PBS-injected mice. On CDE, massive KC activation
      was observed in the PBS group, but this was blunted in CLO-treated mice. The
      depletion of KC did not influence LPC proliferation but reduced their invasive
      behavior. Instead of being found far into the parenchyma, as was found in the PBS
      group (mean distance from portal vein: 209 MUm), LPC of CLO mice remained closer
      to the portal area (138 MUm), forming aggregates and phenotypically resembling
      cells of biliary lineage. Notably, removal of KC was also associated with a
      significant decrease in amount of MF and ECM and in the expression of profibrotic
      factors. Thus, besides ECM and MF, KC are also a significant component of the
      microenvironmental changes preceding LPC expansion. Depletion of KC may limit the
      LPC parenchymal invasion through a deficiency in chemoattracting factors, reduced
      activation of MF, and/or a paucity of the ECM framework necessary for cell
      motility.

PMID- 21854753
TI  - CSF1 expression in nongynecological leiomyosarcoma is associated with increased
      tumor angiogenesis.
AB  - Leiomyosarcoma (LMS) is a malignant tumor of smooth muscle cells for which few
      effective therapies exist. A subset of LMS cases express macrophage colony
      stimulating factor (CSF1) and the resultant tumor-associated macrophage (TAM)
      infiltration predicts poor clinical outcome. Further, TAMs have been shown to
      increase tumor angiogenesis. Here, we analyzed 149 LMS cases by
      immunohistochemistry for vascular marker CD34 and show that high microvessel
      density (MVD) in nongynecological LMS cases significantly predicts poor patient
      outcome. The majority of high MVD cases were also CSF1-positive, and when
      combining high MVD with CSF1 expression, an even stronger prognostic correlation
      with patient outcome was obtained. Gene expression profiling revealed that MVD
      has a stronger correlation with CSF1 expression than with expression of vascular
      endothelial growth factor isoforms, which have traditionally been used as markers
      of angiogenesis and as anti-angiogenic therapeutic targets. Finally, patterns of
      CSF1 expression and TAM recruitment remained consistent between primary tumors
      and their metastases, and between primary tumors and those grown as xenografts in
      mice, highlighting the stability of these features to the biology of LMS tumors.
      Together, these findings suggest an important role for CSF1 and the resulting TAM
      infiltration in the pathological neovascularization of LMS tumors and provide a
      rationale for CSF1-targeted therapies in LMS.

PMID- 21854755
TI  - Revisiting the optimal c value for isothermal titration calorimetry.
AB  - The precision with which the dissociation constant, K(D), can be obtained from
      isothermal titration calorimetry depends on, among other factors, the
      concentrations of the interacting species. The so-called c value-the ratio of
      analyte concentration to K(D)-should fall in the range of 1 to 1000 for reliable
      K(D) determination. On the basis of simulated, noise-free data, Biswas and
      Tsodikov [5] recently suggested an optimal c value of 5 to 20. By contrast, we
      find an optimum at c > 40 on determining the K(D) confidence intervals through
      simulations containing noise levels typical of state-of-the-art
      microcalorimeters.

PMID- 21854754
TI  - Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this
      response is associated with tumor growth and an unfavorable outcome.
AB  - Our objective was to investigate whether the presence of a tumor increases
      hyaluronan (HA) levels in surrounding prostate tissues and whether this
      extratumoral HA influences tumor growth and outcome. From a series of 287 men
      diagnosed with prostate cancer at transurethral resection and followed up with
      watchful waiting, tissue microarrays were constructed, stained, and scored for
      HA. A high HA staining score in the tumor stroma or in nonmalignant prostate
      tissue stroma were both associated positively with higher Gleason score and
      larger tumor volume, and was associated with a poor outcome. HA staining score
      was not an independent marker for outcome (multivariate Cox, with Gleason score,
      tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer
      model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in
      normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer
      growth was increased by intraprostatic injection of HA. In conclusion, cancer in
      the prostate apparently stimulates HA synthesis both in tumor stroma and in the
      surrounding normal tissue. This promoted tumor growth and was associated with an
      unfavorable outcome.

PMID- 21854756
TI  - Enforcing the positive charge of N-termini enhances membrane interaction and
      antitumor activity of bovine seminal ribonuclease.
AB  - Binding to cell membrane, followed by translocation into the cytosol and RNA
      degradation, is a necessary requirement to convert a ribonuclease into a
      cytotoxin for malignant tumor cells. In this paper, we investigate the membrane
      binding attitude of bovine seminal ribonuclease (BS-RNase) and its variant G38K
      BS-RNase, bearing an enforced cluster of positive charges at the N-termini
      surface. By using a combination of biophysical techniques, including CD, SPR and
      ESR, we find for the two proteins a common, two-step mechanism of interaction
      with synthetic liposomes, an initial binding to the bilayer surface, driven by
      electrostatic interactions, followed by a shallow penetration in the lipid core.
      Protein binding effectively perturbs lipid packing and dynamics. Remarkably, the
      higher G38K-BS-RNase membrane interacting capability well correlates with its
      increased cytotoxicity for tumor cells. Overall, these studies shed light on the
      mechanism of membrane binding and perturbation, proving definitely the importance
      of electrostatic interactions in the cytotoxic activity of BS-RNase, and provide
      a rational basis to design proteins with anticancer potential.

PMID- 21854757
TI  - Differential expression of human riboflavin transporters -1, -2, and -3 in
      polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake.
AB  - Transport of riboflavin (RF) across both the brush border membrane (BBM) and
      basolateral membrane (BLM) of the polarized enterocyte occurs via specific
      carrier-mediated mechanisms. Although, three human riboflavin transporters
      (hRFTs), i.e., hRFT-1, hRFT-2 and hRFT-3 are expressed in the intestine, little
      is known about the cell surface domain(s) at which these specific hRFTs are
      expressed. Here, we used live cell confocal imaging of intestinal epithelial Caco
      2 and renal MDCK cells to show that the hRFT-1 is mainly expressed at the BLM,
      hRFT-2 is exclusively expressed at the apical membrane, while hRFT-3 is mostly
      localized inside intracellular vesicular structures (with some expression at the
      BLM). Further the level of hRFT-2 mRNA expression in Caco-2 cells and in native
      human intestine is significantly higher than that of hRFT-1 and -3; hRFT-2 was
      also more efficient in transporting 3H-RF than hRFT-1 and -3. These findings
      implied an important role for hRFT-2 in intestinal RF uptake, a conclusion that
      was further supported by findings of hRFT-2 gene-specific siRNA knockdown
      investigation. These results show that members of the hRFT family are
      differentially expressed in polarized epithelia, and that the apically expressed
      hRFT-2 plays a key role in intestinal RF accumulation.

PMID- 21854758
TI  - Constitutive stabilization of beta-catenin in the dental mesenchyme leads to
      excessive dentin and cementum formation.
AB  - Wnt/beta-catenin signaling plays an important role in morphogenesis and cellular
      differentiation during development. Essential roles of Wnt/beta-catenin signaling
      in tooth morphogenesis have been well known, but the involvement of Wnt/beta
      catenin signaling in the dental hard tissue formation remains undefined. To
      understand roles of Wnt/beta-catenin signaling in dentin and cementum formation,
      we generated and analyzed the conditional beta-catenin stabilized mice in the
      dental mesenchyme. The OC-Cre;Catnb(lox(ex3)/+) mice exhibited malformed teeth
      characterized by aberrantly formed dentin and excessively deposited cementum.
      Large amount of dentin was rapidly formed with widened predentin and numerous
      globular calcifications in the crown. Whereas roots of molars were short and
      covered with the excessively formed cellular cementum. With age, the coronal pulp
      chamber and periodontal space were narrowed by the excessively formed dentin and
      cementum, respectively. To compare the changes of gene expression in the mutant
      mice, Col1a1 expression was increased but that of Dspp was decreased in the
      odontoblasts. However, both of Col1a1 and Bsp expression was increased in the
      cementoblasts. The gene expression changes were consistent with the localization
      of matrix proteins. Biglycan and PC-1 was increased but Phex was decreased in the
      odontoblasts and dentin matrix, respectively. TNAP was increased but Dmp1 and
      FGF23 was decreased in the cementoblasts and cementum matrix, respectively. Our
      results indicate that persistent stabilization of beta-catenin in the dental
      mesenchyme leads to premature differentiation of odontoblasts and differentiation
      of cementoblasts, and induces excessive dentin and cementum formation in vivo.
      These results suggest that temporospatial regulation of Wnt/beta-catenin
      signaling plays critical roles in the differentiation of odontoblasts and
      cementoblasts, and that inhibition of Wnt/beta-catenin signaling may be important
      for the formation of dentin and cementum during tooth development. Local
      modulation of Wnt/beta-catenin signaling has therapeutic potential to improve the
      regeneration of dentin and periodontium.

PMID- 21854759
TI  - DPP-4 inhibitor des-F-sitagliptin treatment increased insulin exocytosis from
      db/db mice beta cells.
AB  - Incretin promotes insulin secretion acutely. Recently, orally-administered DPP-4
      inhibitors represent a new class of anti-hyperglycemic agents. Indeed, inhibitors
      of dipeptidyl peptidase-IV (DPP-4), sitagliptin, has just begun to be widely used
      as therapeutics for type 2 diabetes. However, the effects of sitagliptin
      treatment on insulin exocytosis from single beta-cells are yet unknown. We
      therefore investigated how sitagliptin-treatment in db/db mice affects insulin
      exocytosis by treating db/db mice with des-F-sitagliptin for 2 weeks. Perfusion
      studies showed that 2 weeks-sitagliptin treatment potentiated insulin secretion.
      We then analyzed insulin granule motion and SNARE protein, syntaxin 1, by TIRF
      imaging system. TIRF imaging of insulin exocytosis showed the increased number of
      docked insulin granules and increased fusion events from them during first-phase
      release. In accord with insulin exocytosis data, des-F-sitagliptin-treatment
      increased the number of syntaxin 1 clusters on the plasma membrane. Thus, our
      data demonstrated that 2-weeks des-F-sitagliptin-treatment increased the fusion
      events of insulin granules, probably via increased number of docked insulin
      granules and that of syntaxin 1 clusters.

PMID- 21854760
TI  - Transcriptional activity of DNMT3B in pancreatic cancer cells: effects of -149 (C
      >T) promoter polymorphism.
AB  - Polymorphic C-to-T change in the promoter region of DNA-methyltransferase-3B
      (DNMT3B) gene is associated with risk of several cancers. The aim of this study
      was to investigate the effect of DNMT3B promoter genetic variant on its
      transcriptional activity and to compare activity in several pancreatic cell
      lines. DNMT3B promoter constructs carrying either -149C allele or -149T allele
      were transiently transfected into pancreatic cancer cells. In promoter assaying,
      carriage of -149T allele showed only a slight activity (1.1-fold) in Mia cells
      (p=0.462). In contrast, significant increase (3.8-fold) in activity of -149T
      allele was shown in SU86.86 pancreatic cancer cells (p=0.0001). These preliminary
      findings suggest that genetic variance may influence DNMT3B expression in
      pancreatic cancer. Further studies are needed.

PMID- 21854761
TI  - Discovery of a novel mechanism of steroid receptor antagonism: WAY-255348
      modulates progesterone receptor cellular localization and promoter interactions.
AB  - WAY-255348 is a potent nonsteroidal progesterone receptor (PR) antagonist
      previously characterized in rodents and nonhuman primates. This report describes
      the novel mechanism by which WAY-255348 inhibits the activity of progesterone.
      Most PR antagonists bind to and block PR action by inducing a unique "antagonist"
      conformation of the PR. However, WAY-255348 lacks the bulky side chains or
      chemical groups that have been associated with the conformation changes of helix
      12 that lead to functional antagonism. We show that WAY-255348 achieves
      antagonist activity by binding to and subsequently preventing progesterone
      induced nuclear accumulation, phosphorylation and promoter interactions of the
      PR. This effect was concentration dependent, as high concentrations of WAY-255348
      alone are able to induce nuclear translocation, phosphorylation and subsequent
      promoter interactions resulting in partial agonist activity at these
      concentrations. However, at lower concentrations where nuclear accumulation and
      phosphorylation are prevented, the progesterone-induced DNA binding is blocked
      along with PR-dependent gene expression. Analysis of the PR conformation induced
      by WAY-255348 using a limited protease digestion assay, suggested that the WAY
      255348 bound PR conformation was similar to that of a progesterone agonist-bound
      PR and distinct from steroidal antagonist-bound PR conformations. Furthermore,
      the recruitment and binding of peptides derived from nuclear receptor co
      activators is consistent with WAY-255348 inducing an agonist-like conformation.
      Taken together, these data suggest that WAY-255348 inhibits PR action through a
      novel molecular mechanism that is distinct from previously studied PR modulators
      and may be a useful tool to further understanding of PR signaling pathways.
      Development of therapeutic molecules with this 'passive' antagonism mechanism may
      provide distinct advantages for patients with reproductive disorders or PR
      positive breast cancers.

PMID- 21854762
TI  - Role of aflatoxin B1 as a risk for primary liver cancer in north Indian
      population.
AB  - OBJECTIVES: The present study was designed to determine whether aflatoxin B1
      (AFB1) exposure has any role to play in hepatocellular carcinoma (HCC) patients
      from northern India. DESIGN AND METHODS: A total of 266 HCC patients and 251
      patients of chronic liver disease without-HCC were enrolled into the study. All
      samples were screened for serological markers for hepatitis B and C infections
      and levels of AFB1 in food and urine samples. RESULTS: A threefold (OR=3.43) and
      five-fold (OR=5.47) increased risk of HCC was observed amongst HBV infection and
      AFB1-levels in food and urine samples, respectively. However, a non-significant
      risk was observed with respect to HCV infection (OR=1.27) and alcohol consumption
      (OR=1.18). A threefold (OR=3.15) increased risk of HCC was observed amongst cases
      of non-viral etiology with respect to urinary AFB1. CONCLUSION: The data provides
      an exposure and disease risk information for establishing intervention studies to
      diminish the impact of aflatoxin exposure in Indian population.

PMID- 21854763
TI  - Serum paraoxonase-3 concentration is associated with the severity of hepatic
      impairment in patients with chronic liver disease.
AB  - OBJECTIVES: Research on paraoxonase-3 (PON3) has been hampered by the lack of
      methods for measurement. This is a pilot study aimed at exploring whether chronic
      liver impairment is associated with changes in serum PON3 concentrations, and to
      know whether this measurement may provide useful information to investigate this
      derangement. DESIGN AND METHODS: We studied 110 patients with chronic liver
      disease (21 minimal changes, 79 chronic hepatitis, 10 cirrhosis) and 356 healthy
      volunteers. Serum PON3 concentration was determined by ELISA using polyclonal
      antibodies generated against a synthetic peptide with a sequence specific to
      PON3. RESULTS: Serum PON3 concentrations were increased in patients with chronic
      hepatitis or cirrhosis and showed significant direct correlations with the degree
      of periportal abnormalities including fibrosis, and with serum FAS (a marker of
      antiapoptosis) concentrations. CONCLUSION: These results suggest that PON3 may
      play a hepatoprotective role against histological alterations and hepatic cell
      apoptosis leading to liver disease.

PMID- 21854764
TI  - Effect of dilution on high-density lipoprotein associated paraoxonase-1 activity.
AB  - OBJECTIVES: To investigate the effects of dilution on high-density lipoprotein
      (HDL) associated paraoxonase-1 (PON1) activity. DESIGN AND METHODS: HDL was
      prepared by ultracentrifugation, diluted with TRIS buffer pH 8.2 (0-128 fold) and
      assayed spectrophotometrically for PON1 activity using paraoxon and phenyl
      acetate. RESULTS: HDL-PON1 activity increased progressively with dilution to over
      200% of the undiluted activity by 128 fold dilution (P<0.001). Conversely HDL
      size decreased. CONCLUSION: These results indicate the urgent need to standardise
      conditions for measuring PON1 activity.

PMID- 21854765
TI  - False-positive ethanol blood concentrations leading to clinical confusion on
      Christmas Day.
AB  - A case of altered consciousness in which ethanol ingestion was one of the
      differential diagnoses is described. Three separate blood samples were conveyed
      to the hospital biochemistry laboratory and each returned a positive value when
      assayed via an indirect, enzymatic method. The family strongly denied alcohol
      ingestion and hence, a few days later, the samples were conveyed to an external
      laboratory using a 'specific', chromatographic method. These samples were all
      reported as negative for ethanol. Alternative causes of altered consciousness
      were restricted by the false-positive ethanol laboratory results.

PMID- 21854766
TI  - Specific roles for the GATA transcription factors end-1 and end-3 during C.
      elegans E-lineage development.
AB  - end-1 and end-3 are GATA transcription factors important for specifying endoderm
      cell fate in Caenorhabditis elegans. Deletion of both factors together results in
      larval arrest, 0% survival and a fate change in the endoderm-specifying E
      lineage. Individual deletions of either factor, however, result in the
      development of viable, fertile adults, with 100% of worms developing to adults
      for end-1(-) and 95% for end-3(-). We sought to quantify the variable phenotypes
      seen in both deletions using automated cell lineaging. We quantified defects in
      cell lifetime, cell movement and division axis in end-3(-) embryos, while
      quantifying perturbations in downstream reporter gene expression in strains with
      homozygous deletions for either gene, showing that each deletion leads to a
      unique profile of downstream perturbations in gene expression and cellular
      phenotypes with a high correlation between early and late defects. Combining
      observations in both cellular and gene expression defects we found that
      misaligned divisions at the E2 stage resulted in ectopic expression of the Notch
      target ref-1 in end-3(-) embryos. Using a maximum likelihood phylogenetic
      approach we found end-1 and end-3 split to form two distinct clades within the
      Caenorhabditis lineage with distinct DNA-binding structures. These results
      indicate that end-1 and end-3 have each evolved into genes with unique functions
      during endoderm development, that end-3(-) embryos have a delay in the onset of E
      lineage cell fate and that end-1 has only a partially penetrant ability to
      activate E lineage fate.

PMID- 21854768
TI  - Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via
      ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl
      2.
AB  - TRAIL resistance in many cancer cells is one of the major problems in TRAIL-based
      cancer therapy. Thus, the agents that can sensitize the tumor cells to TRAIL
      mediated apoptosis are strictly needed for the improvement of anti-cancer effect
      of TRAIL. Acrolein is a byproduct of lipid peroxidation, which has been involved
      in pulmonary, cardiac and neurodegenerative diseases. We investigated whether
      acrolein, an alpha,beta-unsaturated aldehyde, can potentiate TRAIL-induced
      apoptosis in human renal cancer cells. The combined treatment with acrolein and
      TRAIL significantly induced apoptosis, and stimulated of caspase-3 activity, DNA
      fragmentation, and cleavage of PARP. We found that acrolein down-regulated the
      protein level of Bcl-2 and Bcl-2 overexpression inhibited the cell death induced
      by the combined treatment with acrolein and TRAIL. In addition, acrolein up
      regulated C/EBP homologous protein (CHOP) and TRAIL death receptor 5 (DR5) and
      down-regulation of CHOP or DR5 expression using the respective small interfering
      RNA significantly attenuated the apoptosis induced by acrolein plus TRAIL.
      Interestingly, pretreatment with an antioxidant, N-acetylcysteine (NAC),
      inhibited not only CHOP and DR5 up-regulation but also the cell death induced by
      acrolein plus TRAIL. Taken together, our results demonstrated that acrolein
      enhances TRAIL-induced apoptosis in Caki cells through down-regulation of Bcl-2
      and ROS dependent up-regulation of DR5.

PMID- 21854767
TI  - Mechanisms underlying impairment of endothelium-dependent relaxation by fetal
      bovine serum in organ-cultured rat mesenteric artery.
AB  - Organ culture of blood vessels provides a useful technique to investigate long
      term effects of drugs because tissue architecture and function are well
      preserved. Various growth factors are responsible for structural and functional
      changes during vascular diseases. We investigated long-term effects of fetal
      bovine serum (FBS) which contains such factors on endothelium-dependent
      relaxation using organ-culture method. Rat isolated mesenteric arteries with
      endothelium were cultured for 3 days without or with 10% FBS (FBS). Acetylcholine
      and bradykinin-induced endothelium-dependent relaxations were significantly
      impaired in FBS, whereas sodium nitroprusside-induced relaxation of endothelium
      removed artery was unchanged. Morphological examination revealed that endothelium
      was intact in FBS. Acetylcholine-induced nitric oxide (NO) release as detected by
      4, 5-diaminofluorescein significantly decreased in FBS, whereas endothelial NO
      synthase expression was unchanged. A Ca(2+) ionophore, A23187-induced relaxation
      was unchanged in FBS. A phospholipase C activator, m-3M3FBS-induced relaxation of
      FBS was unchanged in either Ca(2+)-containing or -free solution. Total
      expressions of transient receptor potential canonical channels (TRPCs: TRPC-1, 
      4, -5) were similar in FBS. These data suggest that FBS impairs endothelium
      dependent relaxation by inhibiting events upstream of phospholipase C activation
      including phospholipase C, G-protein, and receptors in endothelium.

PMID- 21854769
TI  - Mechanical stretch augments insulin-induced vascular smooth muscle cell
      proliferation by insulin-like growth factor-1 receptor.
AB  - Insulin resistance and hypertension have been implicated in the pathogenesis of
      cardiovascular disease; however, little is known about the roles of insulin and
      mechanical force in vascular smooth muscle cell (VSMC) remodeling. We
      investigated the contribution of mechanical stretch to insulin-induced VSMC
      proliferation. Thymidine incorporation was stimulated by insulin in stretched
      VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose
      incorporation in both stretched and un-stretched VSMCs. Mechanical stretch
      augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt
      phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine
      kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as
      thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected
      by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)
      1 receptor expression, although it did not alter the expression of insulin
      receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt
      activation, and thymidine incorporation were inhibited by siRNA for the IGF-1
      receptor. Mechanical stretch augments insulin-induced VSMC proliferation via
      upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and
      Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was
      also augmented in hypertensive rats. These results provide a basis for clarifying
      the molecular mechanisms of vascular remodeling in hypertensive patients with
      hyperinsulinemia.

PMID- 21854771
TI  - Overview of Cytochrome P450 1B1 gene mutations in patients with primary
      congenital glaucoma.
AB  - The objective of this study was to investigate the distribution of mutations in
      the Cytochrome P450 1B1 gene (CYP1B1) in patients with primary congenital
      glaucoma (PCG) among different populations. All identifiable original studies on
      CYP1B1 gene mutations of patients with PCG were reviewed. Finally, DNA mutations
      within the CYP1B1 gene were identified in 542 patients with PCG according to 52
      scientific articles and 147 distinct mutations were found. The 3987G>A (G61E)
      missense mutation is a founder mutation in Middle Eastern population, responsible
      for 45.52% of CYP1B1 mutations. In Gypsies, missense mutation 7996G>A (E387K)
      seems to be a founder mutation, accounting for 79.63% of CYP1B1 mutations. It
      seems that there is no founder mutation in Asian or Caucasian population, but
      also accumulates in some spots. Mutations 7927G>A (V364M), 7990C>T (L385F) and
      8006G>A (R390H) are common in Asian population. In Caucasians, 7940G>A (R368H),
      8037dup10, 8006G>A (R390H), 7901del13, 4340delG, 3987G>A (G61E), 7996G>A (E387K),
      4490G>A (E229K) and 8005C>T/A (R390C/S) are common mutations. The findings
      suggest that ethnic differences and the geographical distribution of PCG may be
      associated with different CYP1B1 mutation patterns. Such information may be
      useful in developing strategies for reliable clinical genetic testing of patients
      with PCG and their families.

PMID- 21854770
TI  - Mammalian ChlR1 has a role in heterochromatin organization.
AB  - The ChlR1 DNA helicase, encoded by DDX11 gene, which is responsible for Warsaw
      breakage syndrome (WABS), has a role in sister-chromatid cohesion. In this study,
      we show that human ChlR1 deficient cells exhibit abnormal heterochromatin
      organization. While constitutive heterochromatin is discretely localized at
      perinuclear and perinucleolar regions in control HeLa cells, ChlR1-depleted cells
      showed dispersed localization of constitutive heterochromatin accompanied by
      disrupted centromere clustering. Cells isolated from Ddx11(-/-) embryos also
      exhibited diffuse localization of centromeres and heterochromatin foci. Similar
      abnormalities were found in HeLa cells depleted of combinations of HP1alpha and
      HP1beta. Immunofluorescence and chromatin immunoprecipitation showed a decreased
      level of HP1alpha at pericentric regions in ChlR1-depleted cells. Trimethyl
      histone H3 at lysine 9 (H3K9-me3) was also modestly decreased at pericentric
      sequences. The abnormality in pericentric heterochromatin was further supported
      by decreased DNA methylation within major satellite repeats of Ddx11(-/-)
      embryos. Furthermore, micrococcal nuclease (MNase) assay revealed a decreased
      chromatin density at the telomeres. These data suggest that in addition to a role
      in sister-chromatid cohesion, ChlR1 is also involved in the proper formation of
      heterochromatin, which in turn contributes to global nuclear organization and
      pleiotropic effects.

PMID- 21854772
TI  - Cellular and 3D optical coherence tomography assessment during the initiation and
      progression of retinal degeneration in the Ccl2/Cx3cr1-deficient mouse.
AB  - Retinal pathologies common to human eye diseases, including abnormal retinal
      pigment epithelial (RPE) cells, drusen-like accumulation, photoreceptor atrophy,
      and choroidal neovascularization, have been reported in the Ccl2/Cx3cr1-deficient
      mouse. The Ccl2 gene encodes the pro-inflammatory chemokine CCL2 (MCP-1), which
      is responsible for chemotactic recruitment of monocyte-derived macrophages to
      sites of inflammation. The Cx3cr1 gene encodes the fractalkine receptor, CX3CR1,
      and is required for accumulation of monocytes and microglia recruited via CCL2.
      Chemokine-mediated inflammation is implicated in retinal degenerative diseases
      such as diabetic retinopathy, age-related macular degeneration, retinitis
      pigmentosa, and uveoretinitis, and proper chemokine signaling from the RPE,
      Muller glia, and astrocytes is necessary to regulate leukocyte trafficking.
      Therefore, this mouse, possessing aberrant chemokine signaling coupled with
      retinal degenerative pathologies, presents an ideal opportunity to investigate
      the effect of altered signaling on retinal homeostasis and photoreceptor
      degeneration. Since this mouse is a recent development, more data covering the
      onset, location, and progression rate of pathologies is needed. In the present
      study we establish these parameters and show two photoreceptor cell death
      processes. Our observations of decreased glutamine synthetase and increased glial
      fibrillary acidic protein suggest that Muller cells respond very early within
      regions where lesions are forming. Finally, we suggest that retinal angiomatous
      proliferation contributes to pathological angiogenesis in this Ccl2/Cx3cr1
      deficient mouse.

PMID- 21854774
TI  - Ups and downs of RNA interference in parasitic nematodes.
AB  - RNA interference (RNAi) is widely used in Caenorhabiditis elegans to identify
      essential gene function. In parasitic nematodes RNAi has been reported to result
      in transcript knockdown of some target genes, but not others, thus limiting its
      use as a potential functional genomics tool. We recently extended work in
      Haemonchus contortus to examine why only some genes seem to be susceptible to
      RNAi and to test RNAi effects in vivo. Here we review our findings, which suggest
      that site of gene expression influences silencing. This most likely reflects
      limited uptake of dsRNA from the environment, a phenomenon also observed in other
      free-living nematodes. We discuss new technologies to improve dsRNA delivery,
      such as nanoparticles being developed for therapeutic siRNA delivery, and methods
      to monitor RNAi effects. Alternative approaches will be important in progressing
      the application of RNAi to identify essential gene function in parasitic
      nematodes.

PMID- 21854775
TI  - Plasmodium falciparum: effect of antimalarial drugs, malaria pigment (beta
      haematin) and Plasmodium falciparum lysate on monocyte GTP-cyclohydrolase 1 gene
      expression.
AB  - In interferon-gamma activated human macrophages, GTP-cyclohydrolase 1 catalyses
      the conversion of guanosine triphosphate to 7,8-dihydroneopterin triphosphate,
      which is dephosphorylated and oxidized to form neopterin. Elevated levels of
      neopterin have been detected in the urine and serum of malaria-infected patients.
      In this study, U937 cells were treated with interferon-gamma and one of the
      following antimalarial drugs: amodiaquine, artemisinin, chloroquine, doxycycline,
      primaquine, pyrimethamine or quinine. The effects of treating the U937 cells with
      malaria pigment (beta-haematin), latex beads, or Plasmodium falciparum-infected
      red blood cell lysates were also investigated. U937 GTP-cyclohydrolase 1 mRNA
      expression was monitored using reverse-transcriptase-quantitative PCR.
      Artemisinin, primaquine, and quinine down-regulated GTP-cyclohydrolase 1 gene
      expression 1.26-, 1.29-, and 1.63-fold, respectively. The remaining drugs had
      insignificant effects. beta-haematin up-regulated GTP-cyclohydrolase 1 mRNA
      expression 1.18-fold, whereas P. falciparum-infected red blood cell lysate down
      regulated expression 1.56-fold. These results show the differing immunomodulatory
      actions of antimalarial drugs and malaria pigment taking place in monocytes.

PMID- 21854776
TI  - The molecular basis of neurodegeneration in multiple sclerosis.
AB  - Studies aimed to elucidate the pathogenesis of the disease and to find new
      therapeutic options for multiple sclerosis (MS) patients heavily rely on
      experimental autoimmune encephalomyelitis (EAE) as a suitable experimental model.
      This strategy has been highly successful for the inflammatory component of the
      disease, but had so far little success in the development of neuroprotective
      therapies, which are also effective in the progressive stage of the disease. Here
      we discuss opportunities and limitations of EAE models for MS research and
      provide an overview on the complex mechanisms leading to demyelination and
      neurodegeneration in this disease. We suggest that the underlying mechanisms
      involve adaptive and innate immunity. However, mitochondrial injury, resulting in
      energy failure, is a key element of neurodegeneration in MS and is apparently
      driven by radical production in activated microglia.

PMID- 21854773
TI  - MUC1/A and MUC1/B splice variants differentially regulate inflammatory cytokine
      expression.
AB  - The frequency of a splice variant of mucin 1 (MUC1), MUC1/A was lower in dry eye
      disease patients compared to normal controls, suggesting a link between the
      absence of MUC1/A and the development of dry eye disease which is characterized
      by chronic inflammation. The objectives of the present study were to clone and
      characterize the phenotype of cells expressing solely MUC1/A versus MUC1/B or a
      variant lacking the extracellular domain (DeltaEX) and to determine whether
      MUC1/A and MUC1/B differentially modulate inflammatory responses in transfected
      cells. The additional 27 bp and SNP present in the N-terminus of MUC1/A were
      cloned into a FLAG-MUC1/B expression vector. Transient transfection of MUC1/A and
      MUC1/B plasmids into MUC1-null COS-7 cells resulted in similar protein expression
      and plasma membrane localization. MUC1/B and MUC1/A differed in their ability to
      modulate tumor necrosis alpha (TNFalpha)-induced transcription of IL-1beta and IL
      8. MUC1/B and MUC1/A inhibited IL-8 induction by TNFalpha at 4 h. However with 24
      h TNFalpha, MUC1/A increased IL-1beta and IL-8 whereas MUC1/B had no effect on
      cytokine expression. MUC1/B inhibited TNFalpha-induced luciferase activity from
      an NF-kappaB reporter whereas MUC1/A either inhibited or increased this
      luciferase activity depending on the time of TNFalpha treatment. MUC1/A, but not
      MUC1/B, increased the basal TGFbeta expression. Both MUC1/B and MUC1/A blocked
      TNFalpha-induced miR-21 expression. These data demonstrate that MUC1/A and MUC1/B
      have different inflammatory activities and support the hypothesis that MUC1
      genotypic differences may affect susceptibility to ocular surface damage in dry
      eye disease.

PMID- 21854777
TI  - A case of mistaken lipoma. Diagnosis: Brunner gland cyst.

PMID- 21854778
TI  - Diversity and host specificity of Blastocystis in syntopic primates on Rubondo
      Island, Tanzania.
AB  - The isolated ecosystem of Rubondo Island National Park, Tanzania is an
      interesting model site, inhabited by an assembly of primate species with various
      histories: two introduced primate species, Pantroglodytes (chimpanzee) and
      Colobus guereza (colobus), and a single indigenous species Chlorocebus aethiops
      pygerythrus (vervet monkey). Apart from important lessons for future
      introduction/re-introduction projects, Rubondo National Park offers a unique
      place to study the patterns of transmission of primate parasites and their host
      specificity. Blastocystis was detected using standard microscopy, together with
      PCR-based determination and the prevalence and subtype identification of
      Blastocystis was determined in each primate species. Subtype (ST) 1 was detected
      in all three Rubondo primate populations; ST2, ST3 and ST5 were found in colobus
      and vervet monkeys. All chimpanzee isolates of Blastocystis belonged exclusively
      to ST1, which formed a discrete group, suggesting that Rubondo chimpanzees are
      colonized by a single, host-specific Blastocystis strain that circulates among
      the members of the group. Phylogenetic analysis indicated that transmission of
      Blastocystis did not occur between Rubondo primate populations. Observed host
      specificity of Blastocystis provides a new understanding of the transmission and
      distribution of Blastocystis among sympatric hosts under natural conditions.

PMID- 21854779
TI  - Characterization of TcHMGB, a high mobility group B family member protein from
      Trypanosoma cruzi.
AB  - High mobility group B (HMGB) proteins are highly abundant non-histone chromatin
      proteins that play important roles in the execution and control of many nuclear
      functions. Based on homology searches, we identified the coding sequence for the
      TcHMGB protein, an HMGB family member from Trypanosoma cruzi. TcHMGB has two HMG
      box domains, similar to mammalian HMGBs, but lacks the typical C-terminal acidic
      tail. Instead, it contains a 110 amino acid long N-terminal domain. The TcHMGB N
      terminal domain is conserved between the TriTryp sequences (70-80% similarity)
      and seems to be characteristic of kinetoplastid HMGBs. Despite these differences,
      TcHMGB maintains HMG box architectural functions: we demonstrated that the
      trypanosomatid HMGB binds distorted DNA structures such as cruciform DNA in gel
      shift assays. TcHMGB is also able to bend linear DNA as determined by T4 ligase
      circularization assays, similar to other HMGB family members. Immunofluorescence
      and western blot assays showed that TcHMGB is a nuclear protein expressed in all
      life cycle stages. Protein levels, however, seem to vary throughout the life
      cycle, which may be related to previously described changes in heterochromatin
      distribution and transcription rates.

PMID- 21854780
TI  - Risk factors for helminth infections in a rural and a peri-urban setting of the
      Dongting Lake area, People's Republic of China.
AB  - Schistosomiasis japonica and soil-transmitted helminthiasis are endemic parasitic
      diseases in the People's Republic of China (PR China). As very few studies have
      reported on the distribution and interaction of multiple species helminth
      infections, we carried out a comparative study of households in a rural village
      and a peri-urban setting in the Dongting Lake area of Hunan province in November
      and December 2006 to determine the extent of single and multiple species
      infections, the underlying risk factors for infection, and the relationships with
      clinical manifestations and self-reported morbidity. In each household, stool
      samples were collected and subjected to the Kato-Katz method for identifying
      Schistosoma japonicum, Ascaris lumbricoides, hookworm and Trichuris trichiura
      infections. Clinical examinations were performed and questionnaire surveys
      conducted at both household and individual subject levels. Complete
      parasitological, clinical and questionnaire data were obtained for 1,298
      inhabitants of the two settings. The overall prevalences of single infections of
      S. japonicum, A. lumbricoides, hookworm and T. trichiura were 6.5%, 5.5%, 3.0%
      and 0.8%, respectively; the majority of the infections were of light intensity.
      We found significant negative associations between wealth and infections with S.
      japonicum and A. lumbricoides. Clinical manifestations of splenomegaly,
      hepatomegaly and anaemia were prevalent (9.0%, 3.7% and 10.9%, respectively), the
      latter two being significantly (P<0.05) associated with schistosomiasis. Self
      reported symptoms were more common among females but there was considerable under
      reporting in both sexes when relying only on spontaneous recall. Our findings may
      guide the design and targeting of a more equitable, comprehensive and integrated
      parasitic disease control programme in Hunan province and in other areas of PR
      China.

PMID- 21854781
TI  - Ex vivo purification and characterization of human invariant Natural Killer T
      cells.
AB  - Natural Killer T (NKT) cells have gained widespread attention among immunologists
      because of their distinct ability to regulate anti-tumor responses and to
      influence the outcome of infections or autoimmunity. Type I (also called
      invariant) NKT cells (iNKT) are best characterized mainly because of the
      availability of lipid antigen-loaded CD1d-tetramer detection reagents. Human iNKT
      cells present important phenotypic differences relative to their murine
      counterpart, restricting the extrapolation of findings from experimental murine
      models to human health and disease states. Particularly, the ontogeny and early
      life phenotype of iNKT cells largely differ between human and mice, indicating
      divergent functional properties between species. The high therapeutic potential
      offered by manipulation of iNKT cells in disease warrants a better understanding
      of human iNKT cell biology. Here, we discuss characteristics of human iNKT cells
      and present an efficient and rapid method for their ex vivo purification and
      characterization.

PMID- 21854782
TI  - Identification of potential human respiratory syncytial virus and metapneumovirus
      T cell epitopes using computational prediction and MHC binding assays.
AB  - Human respiratory syncytial virus (RSV) and human metapneumovirus (MPV) are two
      of the most common causes of serious viral lower respiratory tract illness in
      humans. CD8+ T cells have been shown to be important in animal models and human
      clinical studies for the clearance of viral infection, and they may contribute in
      part to protection against severe disease during reinfections. Precise
      enumeration and accurate phenotyping of RSV- or MPV-specific CD8+ T cells in
      humans is currently limited by the relatively small number of T cell epitopes
      that have been mapped with accompanying identification of MHC restriction
      patterns. We sought to expand the number of potential RSV and MPV epitopes for
      use in clinical and translational studies by identifying an expanded set of MHC
      binding peptides based on RSV and MPV wild-type virus strain protein sequences.
      We interrogated the full protein sequences of all 9 or 11 proteins of MPV or RSV
      respectively using four established epitope prediction algorithms for human HLA
      A*0101, A*0201, or B*0702 binding and attempted to synthesize the top-scoring 150
      152 peptides for each of the two viruses. Synthesis resulted in 442 synthesized
      and soluble peptides of the 452 predicted epitopes for MPV or RSV. We then
      determined the binding of the synthetic peptides to recombinant human HLA A*0101,
      A*0201 or B*0702 molecules with the predicted restriction using a commercially
      available plate-based assay, iTopia. A total of 230 of the 442 peptides tested
      exhibited binding to the appropriate MHC molecule. The binding results suggested
      that existing algorithms for prediction of MHC A*0201 binding are particularly
      robust. The binding results also provided a large benchmarking data collection
      for comparison of new prediction algorithms.

PMID- 21854783
TI  - Hepatospora eriocheir (Wang and Chen, 2007) gen. et comb. nov. infecting invasive
      Chinese mitten crabs (Eriocheir sinensis) in Europe.
AB  - We describe a microsporidian parasite infecting non-native Chinese mitten crabs
      (Eriochier sinensis) from Europe. Electron microscopy revealed merogonic and
      sporogonic life stages bound within a plasmalemma. The crab parasite develops
      polar tube precursors at the sporont stage but does not complete formation of the
      intact spore extrusion apparatus at the stage of the sporogonial plasmodium like
      Enterocytozoon bienuesi and other representatives of the Enterocytozoonidae. Its
      presence within an aquatic crustacean host, and a distinct molecular phylogeny
      based on partial small subunit ribosomal RNA (SSU rRNA) gene sequences also place
      it relatively close, though distinct to, existing genera within the
      Enterocytozoonidae. Consideration of morphological and phylogenetic
      characteristics of other hepatopancreas-infecting microsporidia from crustaceans
      suggests that certain ones (e.g. Enterospora canceri) are retained within the
      clade corresponding to the existing family Enterocytozoonidae, while others,
      including the parasite described here, may eventually be grouped in a sister
      taxon potentially of family rank. Based upon morphological and host similarity,
      it is likely that the parasite described here is the same as Endoreticulatus
      eriocheir (Wang and Chen, 2007), previously described from Chinese mitten crabs
      in Asia. However, using a combined taxonomic approach based upon morphological
      and phylogenetic data, we propose the formation of a new genus (Hepatospora) to
      replace the previous generic classification of the Asian parasite as
      Endoreticulatus. The microsporidian from the hepatopancreas of E. sinensis is
      named Hepatospora eriocheir (Wang and Chen, 2007) gen. et comb. nov. It is
      assumed that the parasite was introduced during initial invasions of this crab to
      Europe during the early 20th Century.

PMID- 21854784
TI  - Heat shock transcription factor 1 protects heart after pressure overload through
      promoting myocardial angiogenesis in male mice.
AB  - Heat shock transcription factor 1 (HSF1) plays an important role not only in
      excise-induced cardiac hypertrophy but also in protection against pressure
      overload-induced cardiac dysfunction. However, the mechanism is not completely
      understood. We here elucidate the potential mechanisms by which HSF1 protects
      against pressure overload-induced cardiac remodeling and dysfunction. A sustained
      constriction of transverse aorta (TAC) was imposed to HSF1 transgenic (TG),
      knockout (KO) and their littermate wild type (WT) male mice. Four weeks later,
      adaptive responses to TAC, such as cardiac hypertrophy, contractility and
      angiogenesis evaluated by echocardiography, catheterization, coronary perfusion
      pressure and immunohistochemistry were well preserved in TG but not in KO
      compared with WT mice. An angiogenesis inhibitor TNP-470 abrogated all these
      adaptive responses in TG mice, while cardiac transfection of VEGF with
      angiopoietin-1 rescued the broken heart in KO mice. In response to TAC, p53 was
      downregulated and hypoxia-inducing transcription factor-1 (HIF-1) was upregulated
      not only in the heart but also in the cultured cardiac endothelial cells (EC) of
      TG mice as compared to WT mice whereas these changes became opposite in KO mice.
      A small interfering RNA (siRNA) of HIF-1 but not a p53 gene impaired the adaptive
      responses of the heart and EC in TG mice, and a siRNA of p53 but not a HIF-1 gene
      significantly reversed the heart and EC disorders in KO mice after TAC. We
      conclude that HSF1 promotes cardiac angiogenesis through suppression of p53 and
      subsequent upregulation of HIF-1 in endothelial cells during chronic pressure
      overload, leading to the maintenance of cardiac adaptation.

PMID- 21854785
TI  - Heart failure drug discovery: scarred or ready for remodeling?

PMID- 21854786
TI  - Mutations and natural selection in the protein world.

PMID- 21854788
TI  - Fractal scaling of laser Doppler flowmetry time series in patients with essential
      hypertension.
AB  - The full diagnostic potential of the fractal complexity measure, alpha, of
      detrended fluctuation analysis (DFA) has not been realized yet. To reveal the
      impaired mechanisms in the blood flow regulation in patients with essential
      hypertension (EHT), we studied the laser Doppler flowmetry (LDF) time series by
      applying DFA. Forearm microvascular blood flow was measured by LDF during supine
      rest. After a 15 min baseline recording, microvascular response to thermal
      hyperemia was measured over 30 min. We found three distinct scaling regions;
      corresponding to the integration of local mechanisms, cardiac effect on local
      blood flow, and the coupling of extrinsic factors (cardiac and respiratory) to
      local blood flow by myogenic mechanism. In the control group, local scaling
      exponent, alpha(L)=0.96 +/- 0.08, did not change but cardiac scaling exponent,
      alpha(C)=1.53 +/- 0.05, for baseline signal was increased to alpha(CT)=1.73 +/-
      0.10 and cardio-respiratory scaling exponent, alpha(CR)=0.73 +/- 0.19, was
      decreased to alpha(CRT)=0.24 +/- 0.06 during vasodilatation in response to local
      heating. However, we found significantly different scaling exponents,
      alpha(LT)<1, alpha(CT) >= alpha(C)<1.5 and alpha(CR) ~ alpha(CRT)>0.5 in patients
      with EHT. Our findings suggest that the local regulatory and the cushioning
      peripheral vascular functions are impaired in patients with EHT, and
      vascular/microvascular pathology can be evaluated by applying DFA to LDF signal.

PMID- 21854787
TI  - Determinants of homodimerization specificity in histidine kinases.
AB  - Two-component signal transduction pathways consisting of a histidine kinase and a
      response regulator are used by prokaryotes to respond to diverse environmental
      and intracellular stimuli. Most species encode numerous paralogous histidine
      kinases that exhibit significant structural similarity. Yet in almost all known
      examples, histidine kinases are thought to function as homodimers. We
      investigated the molecular basis of dimerization specificity, focusing on the
      model histidine kinase EnvZ and RstB, its closest paralog in Escherichia coli.
      Direct binding studies showed that the cytoplasmic domains of these proteins each
      form specific homodimers in vitro. Using a series of chimeric proteins, we
      identified specificity determinants at the base of the four-helix bundle in the
      dimerization and histidine phosphotransfer domain. Guided by molecular
      coevolution predictions and EnvZ structural information, we identified sets of
      residues in this region that are sufficient to establish homospecificity.
      Mutating these residues in EnvZ to the corresponding residues in RstB produced a
      functional kinase that preferentially homodimerized over interacting with EnvZ.
      EnvZ and RstB likely diverged following gene duplication to yield two homodimers
      that cannot heterodimerize, and the mutants we identified represent possible
      evolutionary intermediates in this process.

PMID- 21854789
TI  - Alterations in hippocampal excitability, synaptic transmission and synaptic
      plasticity in a neurodevelopmental model of schizophrenia.
AB  - The risk of developing schizophrenia has been linked to perturbations in
      embryonic development, but the physiological alterations that result from such
      insults are incompletely understood. Here, we have investigated aspects of
      hippocampal physiology in a proposed neurodevelopmental model of schizophrenia,
      induced during gestation in rats by injection of the antimitotic agent
      methylazoxymethanol acetate (MAM) at embryonic day 17 (MAM(E17)). We observed a
      reduction in synaptic innervation and synaptic transmission in the dorsal
      hippocampus of MAM(E17) treated rats, accompanied by a pronounced increase in CA1
      pyramidal neuron excitability. Pharmacological investigations suggested that a
      deficit in GABAergic inhibition could account for the increase in excitability;
      furthermore, some aspects of the hyper-excitability could be normalised by the
      GABA(A) receptor (GABA(A)R) potentiator diazepam. Despite these alterations, two
      major forms of synaptic plasticity, long-term potentiation (LTP) and long-term
      depression (LTD) could be readily induced. In contrast, there was a substantial
      deficit in the reversal of LTP, depotentiation. These findings suggest that
      delivering neurodevelopmental insults at E17 may offer insights into some of the
      physiological alterations that underlie behavioural and cognitive symptoms
      observed in schizophrenia.

PMID- 21854790
TI  - Rat hippocampal somatostatin sst3 and sst4 receptors mediate anticonvulsive
      effects in vivo: indications of functional interactions with sst2 receptors.
AB  - Somatostatin-14 (SRIF) is a potent anticonvulsant in rodent models of limbic
      seizures in which the hippocampus is its major site of action. However, the
      distribution of hippocampal sst receptors and their role in the anticonvulsant
      effects of SRIF remain controversial. Moreover, striking differences have been
      described between mice and rats. In rats, sst(2) but not sst(1) receptors play a
      critical role in the anticonvulsant effects of SRIF. At present, the role of rat
      sst(3) and sst(4) receptors in these anticonvulsive effects remains unknown. Here
      we demonstrate in vivo anticonvulsive actions of rat hippocampal sst(3) and
      sst(4) receptors. Using microdialysis and telemetry-based electroencephalographic
      recordings we show that intrahippocampal administration of the sst(2) agonist L
      779,976 (500 nM), the sst(3) agonist L-796,778 (100 nM) or the sst(4) agonist L
      803,087 (100 nM) protects rats against focal pilocarpine-induced seizures. SRIF
      (1 MUM)-, sst(3)- and sst(4)-mediated anticonvulsive actions are reversed by the
      selective sst(2) receptor antagonist cyanamid 154806 (100 nM). Moreover, the
      selective sst(3) antagonist SST3-ODN-8 (100 nM) blocks the sst(4)-mediated
      anticonvulsant effect. Sst(3) antagonism does not reverse the sst(2)- or SRIF
      mediated anticonvulsant effects. Our findings provide the first in vivo evidence
      for potent anticonvulsive properties of sst(3) and sst(4) receptors in the rat
      hippocampus. Nevertheless, selective sst(2) receptor antagonism prevented these
      sst(3)- or sst(4) receptor-mediated anticonvulsant effects, suggesting a
      functional cooperation with rat hippocampal sst(2) receptors.

PMID- 21854792
TI  - Hyperforin changes the zinc-storage capacities of brain cells.
AB  - In vitro and in vivo experiments were carried out to investigate the consequences
      on brain cells of a chronic treatment with hyperforin, a plant extract known to
      dissipate the mitochondrial membrane potential and to release Zn(2+) and Ca(2+)
      from these organelles. Dissociated cortical neurons were grown in a culture
      medium supplemented with 1 MUM hyperforin. Live-cell imaging experiments with the
      fluorescent probes FluoZin-3 and Fluo-4 show that a 3 day-hyperforin treatment
      diminishes the size of the hyperforin-sensitive pools of Ca(2+) and Zn(2+)
      whereas it increases the size of the DTDP-sensitive pool of Zn(2+) without
      affecting the ionomycin-sensitive pool of Ca(2+). When assayed by quantitative
      PCR the levels of mRNA coding for metallothioneins (MTs) I, II and III were
      increased in cortical neurons after a 3 day-hyperforin treatment. This was
      prevented by the zinc chelator TPEN, indicating that the plant extract controls
      the expression of MTs in a zinc-dependent manner. Brains of adult mice who
      received a daily injection (i.p.) of hyperforin (4 mg/kg/day) for 4 weeks had a
      higher sulphur content than control animals. They also exhibited an enhanced
      expression of the genes coding for MTs. However, the long-term treatment did not
      affect the brain levels of calcium and zinc. Based on these results showing that
      hyperforin influences the size of the internal pools of Zn(2+), the expression of
      MTs and the brain cellular sulphur content, it is proposed that hyperforin
      changes the Zn-storage capacity of brain cells and interferes with their thiol
      status.

PMID- 21854791
TI  - Differential effects of mGluR7 and mGluR8 activation on pain-related synaptic
      activity in the amygdala.
AB  - Pain-related plasticity in the laterocapsular division of the central nucleus of
      the amygdala (CeLC) depends on the activation of group I metabotropic glutamate
      receptors (mGluRs) whereas groups II and III mGluRs generally serve inhibitory
      functions. Recent evidence suggests differential roles of group III subtypes
      mGluR7 (pain enhancing) and mGluR8 (pain inhibiting) in the amygdala (Palazzo et
      al., 2008). Here we addressed the underlying synaptic mechanisms of mGluR7 and
      mGluR8 function in the CeLC under normal conditions and in an arthritis pain
      model. Using patch-clamp recordings in rat brain slices, we measured monosynaptic
      excitatory post-synaptic currents (EPSCs), mono- and polysynaptic inhibitory
      synaptic currents (IPSCs), and synaptically evoked action potentials (E-S
      coupling) in CeLC neurons. Synaptic responses were evoked by electrical
      stimulation in the basolateral amygdala (BLA). A selective mGluR8 agonist (DCPG)
      inhibited evoked EPSCs and synaptic spiking more potently in slices from
      arthritic rats than in slices from normal rats. In contrast, a selective mGluR7
      agonist (AMN082) increased EPSCs and E-S coupling in slices from normal rats but
      not in the pain model. The effects of AMN082 and DCPG were blocked by a group III
      antagonist (MAP4). AMN082 increased frequency, but not amplitude, of spontaneous
      EPSCs but had no effect on miniature EPSCs (in TTX). DCPG decreased frequency,
      but not amplitude, of spontaneous and miniature EPSCs. The data suggest that
      mGluR8 acts presynaptically to inhibit excitatory transmission whereas the
      facilitatory effects of mGluR7 are indirect through action potential-dependent
      network action. AMN082 decreased evoked IPSCs and frequency, but not amplitude,
      of spontaneous and miniature IPSCs in slices from normal rats. DCPG had no effect
      on inhibitory transmission. The results suggest that presynaptic mGluR7 inhibits
      inhibitory synaptic transmission to gate glutamatergic transmission to CeLC
      neurons under normal conditions but not in pain. Presynaptic mGluR8 inhibits pain
      related enhanced excitatory transmission in the CeLC.

PMID- 21854793
TI  - Dopamine activation in Neuroticism as measured by spontaneous eye blink rate.
AB  - Personality dimensions have been associated with different psychobiological
      systems. However, no agreement exists in literature on a specific role of a
      single neurotransmitter for each of the dimensions investigated. We studied the
      relationship of Neuroticism, Extraversion and Psychoticism as assessed by Eysenck
      Personality Inventory (EPI) with spontaneous eye blink rate (BR), a non-invasive
      measure of central dopamine activity. A total of sixty-three healthy subjects (40
      females, 23 males, mean age 24.2+/-3.9) were studied. Spontaneous blink rate and
      time of blink suppression were assessed by EOG measurement. Levels of
      Extraversion and Neuroticism were inversely correlated. In contrast with previous
      findings, a significant correlation between blink rate measures and Neuroticism
      was found. No significant correlation between blink measures and either
      Extraversion, or Psychoticism were found. The results appear consistent with a
      lower threshold for activation in neuroticism as suggested by Eysenck's original
      model.

PMID- 21854794
TI  - Dehydration-anorexia derives from a reduction in meal size, but not meal number.
AB  - The anorexia that results from extended periods of cellular dehydration is an
      important physiological adaptation that limits the intake of osmolytes from food
      and helps maintain the integrity of fluid compartments. The ability to
      experimentally control both the development and reversal of anorexia, together
      with the understanding of underlying hormonal and neuropeptidergic signals, makes
      dehydration (DE)-anorexia a powerful model for exploring the interactions of
      neural networks that stimulate and inhibit food intake. However, it is not known
      which meal parameters are affected by cellular dehydration to generate anorexia.
      Here we use continuous and high temporal resolution recording of food and fluid
      intake, together with a drinking-explicit method of meal pattern analysis to
      explore which meal parameters are modified during DE-anorexia. We find that the
      most important factor responsible for DE-anorexia is the failure to maintain
      feeding behavior once a meal has started, rather than the ability to initiate a
      meal, which remains virtually intact. This outcome is consistent with increased
      sensitivity to satiation signals and post-prandial satiety mechanisms. We also
      find that DE-anorexia significantly disrupts the temporal distribution of meals
      across the day so that the number of nocturnal meals gradually decreases while
      diurnal meal number increases. Surprisingly, once DE-anorexia is reversed this
      temporal redistribution is maintained for at least 4 days after normal food
      intake has resumed, which may allow increased daily food intake even after normal
      satiety mechanisms are reinstated. Therefore, DE-anorexia apparently develops
      from a selective targeting of those neural networks that control meal
      termination, whereas meal initiation mechanisms remain viable.

PMID- 21854795
TI  - Reduction of isoprenaline-induced myocardial TGF-beta1 expression and fibrosis in
      osthole-treated mice.
AB  - Peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma ligands can
      attenuate myocardial fibrosis. Osthole, an active constituent isolated from the
      fruit of Cnidium monnieri (L.) Cusson, may be a dual PPARalpha/gamma agonist, but
      there has been no report on its effect on myocardial fibrosis. In the present
      study, we investigated the inhibitory effect of osthole on myocardial fibrotic
      formation in mice and its possible mechanisms. A mouse model with myocardial
      fibrosis was induced by hypodermic injection of isoprenaline while the mice were
      simultaneously treated with 40 and 80 mg/kg osthole for 40 days. After the
      addition of osthole, the cardiac weight index and hydroxyproline content in the
      myocardial tissues were decreased, the degree of collagen accumulation in the
      heart was improved, and the downregulation of myocardial PPARalpha/gamma mRNA
      expression induced by isoprenaline was reversed. Moreover, the mRNA expression of
      transforming growth factor (TGF)-beta1 and the protein levels of nuclear factor
      (NF)-kappaB and TGF-beta1 in the myocardial tissues were decreased. These
      findings suggest that osthole can prevent isoprenaline-induced myocardial
      fibrosis in mice, and its mechanisms may be related to the reduction of TGF-beta1
      expression via the activation of PPARalpha/gamma and subsequent inhibition of NF
      kappaB in myocardial tissues.

PMID- 21854796
TI  - Reactive oxygen species mediate arsenic induced cell transformation and
      tumorigenesis through Wnt/beta-catenin pathway in human colorectal adenocarcinoma
      DLD1 cells.
AB  - Long term exposure to arsenic can increase incidence of human cancers, such as
      skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is
      still unclear. It is generally believed that reactive oxygen species (ROS) may
      play an important role in this process. In the present study, we investigate the
      possible linkage between ROS, beta-catenin and arsenic induced transformation and
      tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our
      results show that arsenic was able to activate p47(phox) and p67(phox), two key
      proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS
      in DLD1 cells. Arsenic increased beta-catenin expression level and its promoter
      activity. ROS played a major role in arsenic-induced beta-catenin activation.
      Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis
      of these cells. The tumor volumes of arsenic treated group were much larger than
      those without arsenic treatment. Addition of either superoxide dismutase (SOD) or
      catalase reduced arsenic induced cell transformation and tumor formation. The
      results indicate that ROS are involved in arsenic induced cell transformation and
      tumor formation possible through Wnt/beta-catenin pathway in human colorectal
      adenocarcinoma cell line DLD1 cells.

PMID- 21854797
TI  - Identification of presynaptic neurotoxin complexes in the venoms of three
      Australian copperheads (Austrelaps spp.) and the efficacy of tiger snake
      antivenom to prevent or reverse neurotoxicity.
AB  - The venom of the Australian lowlands copperhead, Austrelaps superbus, produces
      significant and potentially lethal neurotoxic paralysis in cases of clinical
      envenomation. However, little is known about the neurotoxic components within
      this venom or venoms from the related alpine copperhead (Austrelaps ramsayi) or
      pygmy copperhead (Austrelaps labialis). Using the isolated chick biventer
      cervicis nerve-muscle preparation, all Austrelaps venoms were found to exhibit
      potent and rapid inhibition of nerve-evoked twitch contractions and block of
      contractures to nicotinic agonists, consistent with postsynaptic neurotoxic
      activity. Following separation by size-exclusion liquid chromatography under non
      denaturing conditions, all Austrelaps venoms were found to also contain a high
      molecular mass fraction with only weak phospholipase A(2) (PLA(2)) activity that
      caused a slow inhibition of twitch contractions, without inhibiting contractures
      to nicotinic agonists. These actions are consistent with the presence of
      additional snake presynaptic PLA(2) neurotoxin (SPAN) complexes in all three
      Austrelaps venoms. However, there was no evidence of direct muscle damage
      produced by any Austrelaps venom or SPAN complex. Monovalent tiger snake
      antivenom was effective in neutralising the neurotoxicity of both whole venom and
      the SPAN complex. However antivenom was unable to effectively reverse whole venom
      neurotoxicity, or prejunctional SPAN neurotoxicity, once established. Given the
      strong neurotoxicity of all Austrelaps venoms, particularly A. ramsayi and A.
      labialis, effective bites from these copperhead species should be considered
      potentially lethal. Furthermore, clinicians need to be aware of possible
      irreversible presynaptic neurotoxicity following envenomation from all copperhead
      species and that early antivenom intervention is important in preventing further
      development of toxicity.

PMID- 21854798
TI  - Report of the 4th International Conference on Envenomations by Snakebites and
      Scorpion Stings in Africa, Dakar, April 25-29, 2011.
AB  - The authors present a summary of the proceedings and the recommendations of the
      the 4th International Conference on Envenomations by Snakebites and Scorpion
      Stings in Africa, held from April 25th to 29th in Dakar. After a two day training
      workshop for Senegalese health personnel on the most relevant aspects of the
      management of envenomations, about 270 participants met to share their
      experiences in the field. Nearly a hundred oral and poster contributions
      concerning the epidemiology of snakebites and scorpion stings in Africa, the
      composition and action of venoms, as well as the manufacture and use of
      antivenoms, were presented and discussed. The last day was devoted to an
      institutional debate joining experts, representatives of national health
      authorities and concerned professionals (physicians, pharmacists, nurses and
      traditional healers) as well as members of the pharmaceutical industry, to
      discuss and elaborate a set of recommendations. It was agreed that it is
      necessary to improve knowledge of the epidemiological situation by case
      reporting. Quality control of anivenoms and procedures for their registration at
      the level of national health authorities should aim at improving the distribution
      of safe and effective antivenoms in peripheral health centers, which bear the
      heaviest burden of cases. It was also recommended that adequate training of
      health personnel in all aspects of medical management of envenomations should
      constitute a priority. Finally, financing mechanisms to ensure an equitable
      distribution of resources must be sought, as well as the constitution of a
      network of African experts were discussed at length.

PMID- 21854799
TI  - Visual function and white matter microstructure in very-low-birth-weight (VLBW)
      adolescents--a DTI study.
AB  - Premature birth is associated with visual impairments, due to both cerebral and
      ocular pathology. This study examined the relationship between cerebral white
      matter microstructure, evaluated by diffusion tensor imaging (DTI), and visual
      function, in 30 preterm born adolescents with very low birth weight (VLBW=birth
      weight?1500g) and an age-matched group of 45 term born controls. Visual acuity
      correlated positively with fractional anisotropy (FA) in corpus callosum and in
      frontal white matter areas in the VLBW participants, but not in the control
      participants. Callosal visual connections may play a more important role in the
      development of good visual acuity than previously acknowledged in preterm born
      children.

PMID- 21854800
TI  - Spatial-frequency cutoff requirements for pattern recognition in central and
      peripheral vision.
AB  - It is well known that object recognition requires spatial frequencies exceeding
      some critical cutoff value. People with central scotomas who rely on peripheral
      vision have substantial difficulty with reading and face recognition.
      Deficiencies of pattern recognition in peripheral vision, might result in higher
      cutoff requirements, and may contribute to the functional problems of people with
      central-field loss. Here we asked about differences in spatial-cutoff
      requirements in central and peripheral vision for letter and face recognition.
      The stimuli were the 26 letters of the English alphabet and 26 celebrity faces.
      Each image was blurred using a low-pass filter in the spatial frequency domain.
      Critical cutoffs (defined as the minimum low-pass filter cutoff yielding 80%
      accuracy) were obtained by measuring recognition accuracy as a function of cutoff
      frequency (in cycles per object). Our data showed that critical cutoffs increased
      from central to peripheral vision by 20% for letter recognition and by 50% for
      face recognition. We asked whether these differences could be accounted for by
      central/peripheral differences in the contrast sensitivity function (CSF). We
      addressed this question by implementing an ideal-observer model which
      incorporates empirical CSF measurements and tested the model on letter and face
      recognition. The success of the model indicates that central/peripheral
      differences in the cutoff requirements for letter and face recognition can be
      accounted for by the information content of the stimulus limited by the shape of
      the human CSF, combined with a source of internal noise and followed by an
      optimal decision rule.

PMID- 21854801
TI  - The context effect in face matching: Effects of feedback.
AB  - Faces are perceived holistically, even when they are presented briefly (Hole,
      1994; Richler, Mack, et al., 2009). Results obtained with a context congruency
      paradigm support dominance of holistic processing for brief timings, but indicate
      that larger viewing times enable observers to regulate contextual influences, and
      to use a feature selective focus (Meinhardt-Injac, Persike, & Meinhardt, 2010).
      Here we provide further evidence for this claim, and illuminate the role of
      feedback. With trial by trial feedback observers show poor performance in
      incongruent facial contexts at brief timings, but become quite effective in
      suppressing information that interferes with the correct judgements at larger
      viewing times. Without feedback they are still able to delimit the effects of
      conflicting contextual information, but are less effective. Adding further target
      features leads to moderate performance increase in incongruent contexts when
      there is no feedback, but to strong improvement when feedback is provided. These
      findings indicate that observers use opportunities of learning to replace
      holistic face perception by modes of active vision when sufficient temporal
      resources are available.

PMID- 21854802
TI  - Hydrogen peroxide targets the cysteine at the active site and irreversibly
      inactivates creatine kinase.
AB  - In our study, we showed that at a relatively low concentration, H(2)O(2) can
      irreversibly inactivate the human brain type of creatine kinase (HBCK) and that
      HBCK is inactivated in an H(2)O(2) concentration-dependent manner. HBCK is
      completely inactivated when incubated with 2mM H(2)O(2) for 1h (pH 8.0, 25
      degrees C). Inactivation of HBCK is a two-stage process with a fast stage
      (k(1)=0.050 +/- 0.002 min(-1)) and a slow (k(2)=0.022 +/- 0.003 min(-1)) stage.
      HBCK inactivation by H(2)O(2) was affected by pH and therefore we determined the
      pH profile of HBCK inactivation by H(2)O(2). H(2)O(2)-induced inactivation could
      not be recovered by reducing agents such as dl-dithiothreitol, N-acetyl-L
      cysteine, and l-glutathione reduced. When HBCK was treated with DTNB, an enzyme
      substrate that reacts specifically with active site cysteines, the enzyme became
      resistant to H(2)O(2). HBCK binding to Mg(2+)ATP and creatine can also prevent
      H(2)O(2) inactivation. Intrinsic and 1-anilinonaphthalene-8-sulfonate-binding
      fluorescence data showed no tertiary structure changes after H(2)O(2) treatment.
      The thiol group content of H(2)O(2)-treated HBCK was reduced by 13%
      (approximately 1 thiol group per HBCK dimer, theoretically). For further insight,
      we performed a simulation of HBCK and H(2)O(2) docking that suggested the CYS283
      residue could interact with H(2)O(2). Considering these results and the
      asymmetrical structure of HBCK, we propose that H(2)O(2) specifically targets the
      active site cysteine of HBCK to inactivate HBCK, but that substrate-bound HBCK is
      resistant to H(2)O(2). Our findings suggest the existence of a previously unknown
      negative form of regulation of HBCK via reactive oxygen species.

PMID- 21854803
TI  - B-lymphopoiesis gains sensitivity to subsequent inhibition by estrogens during
      final phase of fetal development.
AB  - Adult B-lymphopoiesis is suppressed by the inhibitory effects of elevated
      estrogens during pregnancy. At the same time, hematopoietic cells in the fetal
      liver are resistant to this suppression by estrogens and ensure active production
      of B-cells. We investigated whether this unresponsiveness to estrogens of fetal
      cells also applies to cells obtained from a newborn liver and projects into the
      adult hematopoiesis when fetal liver cells are transplanted to adult mice.
      Mixtures of fetal liver (E14.5), neonatal liver (P0.5) and adult bone marrow (BM)
      cells were co-transplanted into adult primary and secondary recipients treated
      with high doses of estrogen in the Ly5.1/Ly5.2 congenic mouse model. Total
      chimerism as a proportion of all nucleated blood cells, chimerism as a proportion
      of B220+ B-cells, and of other blood cell lineages as well, were determined by
      flow cytometry. B-lymphopoiesis derived from fetal liver (E14.5) stem cells
      remained resistant to estrogen after transplantation into both primary and
      secondary adult recipients, for up to 280 days. In contrast, B-lymphopoiesis
      derived from neonatal liver (P0.5) stem cells was resistant to estrogen only for
      approximately 50 days after the primary transplantation to the adult BM
      microenvironment. These results provide further evidence for a critical
      developmental period of B-lymphopoiesis during its fetal liver stage. In the
      mouse, critical developmental events that allow for the subsequent expressed
      sensitivity of B-lymphopoiesis for suppression by estrogens after sexual
      maturation appear to occur during the period of late-stage fetal liver
      hematopoiesis before its migration to the bone marrow.

PMID- 21854804
TI  - Vectors for ligation-independent construction of lacZ gene fusions and cloning of
      PCR products using a nicking endonuclease.
AB  - Several ligation-independent cloning methods have been developed that offer
      advantages for construction of recombinant plasmids at high efficiency while
      minimizing cloning artifacts. Here we report new plasmid vectors that use the
      nicking endonuclease Nt.BspQI to generate extended single stranded tails for
      direct cloning of PCR products. The vectors include pLacCOs1, a ColE1-derivative
      plasmid imparting resistance to ampicillin, which allows facile construction of
      lacZ translational fusions and pKanCOs1, a pSC101-derivative cloning vector that
      imparts resistance to kanamycin, for cloning of PCR amplicons from genomic DNA as
      well as from ampicillin-based plasmids. We have successfully used these plasmids
      to directionally clone and characterize bacterial promoters that exhibit
      temperature regulated expression, as well as for cloning a variety of PCR
      products. In all cases, constructs with the correct configurations were generated
      at high efficiency and with a minimal number of manipulations. The cloning
      vectors can also be easily modified to incorporate additional reporter genes or
      to express epitope-tagged gene products.

PMID- 21854805
TI  - Computed tomography findings in invasive pulmonary aspergillosis in non
      neutropenic transplant recipients and neutropenic patients, and their prognostic
      value.
AB  - OBJECTIVES: We evaluated CT findings and their prognostic value in non
      neutropenic transplant recipients with invasive pulmonary aspergillosis (IPA)
      compared with neutropenic patients with IPA. METHODS: All adult patients during a
      27-month who met the criteria for proven or probable IPA according to the 2008
      EORTC/MSG criteria were retrospectively enrolled. Initial CT findings were
      reviewed by two radiologists blinded to the patients' demographics and clinical
      outcomes. RESULTS: A total of 50 non-neutropenic transplant recipients and 60
      neutropenic patients were enrolled. Consolidation-or-mass, halo signs, and angio
      invasive form were observed less often in non-neutropenic transplant recipients
      than in neutropenic patients: (56%, 26%, and 32%) versus (78%, 55%, and 60%, p =
      0.01, p = 0.002, and p = 0.003, respectively). Multivariate analysis revealed
      that macronodules (HR 0.31, p = 0.001), multiple infarct-shaped consolidations
      (HR 4.26, p < 0.001), renal replacement therapy (HR 5.62, p < 0.001) and
      persistence of a positive serum galactomannan (HR 7.14, p < 0.001) were
      independently associated with 90-day mortality. CONCLUSIONS: Our data indicate
      that CT findings in non-neutropenic transplant recipients with IPA are similar to
      those in neutropenic patients with IPA except that consolidation-or-mass, halo
      sings, and angio-invasive form are less frequent, and certain CT findings such as
      macronodules and multiple infarct-shaped consolidations have prognostic
      implications in IPA.

PMID- 21854806
TI  - Quantitation of infectious myonecrosis virus in different tissues of naturally
      infected Pacific white shrimp, Litopenaeus vannamei, using real-time PCR with
      SYBR Green chemistry.
AB  - The Pacific white shrimp, Litopenaeus vannamei, is the most important shrimp
      species in volume in world aquaculture. However, in recent decades, outbreaks of
      diseases, especially viral diseases, have led to significant economic losses,
      threatening the sustainability of shrimp farming worldwide. In 2004, Brazilian
      shrimp farming was seriously affected by a new disease caused by the Infectious
      myonecrosis virus (IMNV). Thus, disease control based on rapid and sensitive
      pathogen detection methods has become a priority. In this study, a specific
      quantitation method for IMNV was developed using real-time PCR with SYBR Green
      chemistry and viral load of the principal target tissues of chronically infected
      animals was quantified. The quantitative analysis revealed that mean viral load
      ranged from 5.08*10(8) to 1.33*10(6)copies/MUg of total RNA in the hemolymph,
      5.096*10(5) to 1.26*10(3)copies/MUg in the pleopods, 6.85*10(8) to
      3.09*10(4)copies/MUg in muscle and 8.15*10(6) to 3.90*10(3)copies/MUg in gills.
      Different viral loads of IMNV were found with greater values in the hemolymph and
      muscle, followed by the pleopods and gills.

PMID- 21854807
TI  - Peptide aldehyde inhibitors challenge the substrate specificity of the SARS
      coronavirus main protease.
AB  - SARS coronavirus main protease (SARS-CoV M(pro)) is essential for the replication
      of the virus and regarded as a major antiviral drug target. The enzyme is a
      cysteine protease, with a catalytic dyad (Cys-145/His-41) in the active site.
      Aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of SARS-CoV
      M(pro). Previous studies using peptidic substrates and inhibitors showed that the
      substrate specificity of SARS-CoV M(pro) requires glutamine in the P1 position
      and a large hydrophobic residue in the P2 position. We determined four crystal
      structures of SARS-CoV M(pro) in complex with pentapeptide aldehydes (Ac-ESTLQ-H,
      Ac-NSFSQ-H, Ac-DSFDQ-H, and Ac-NSTSQ-H). Kinetic data showed that all of these
      aldehydes exhibit inhibitory activity towards SARS-CoV M(pro), with K(i) values
      in the MUM range. Surprisingly, the X-ray structures revealed that the
      hydrophobic S2 pocket of the enzyme can accommodate serine and even aspartic-acid
      side-chains in the P2 positions of the inhibitors. Consequently, we reassessed
      the substrate specificity of the enzyme by testing the cleavage of 20 different
      tetradecapeptide substrates with varying amino-acid residues in the P2 position.
      The cleavage efficiency for the substrate with serine in the P2 position was 160
      times lower than that for the original substrate (P2=Leu); furthermore, the
      substrate with aspartic acid in the P2 position was not cleaved at all. We also
      determined a crystal structure of SARS-CoV M(pro) in complex with aldehyde Cm-FF
      H, which has its P1-phenylalanine residue bound to the relatively hydrophilic S1
      pocket of the enzyme and yet exhibits a high inhibitory activity against SARS-CoV
      M(pro), with K(i)=2.24+/-0.58 MUM. These results show that the stringent
      substrate specificity of the SARS-CoV M(pro) with respect to the P1 and P2
      positions can be overruled by the highly electrophilic character of the aldehyde
      warhead, thereby constituting a deviation from the dogma that peptidic inhibitors
      need to correspond to the observed cleavage specificity of the target protease.

PMID- 21854808
TI  - Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal
      dengue virus infection.
AB  - Dengue virus infection causes diseases in people, ranging from the acute febrile
      illness dengue fever, to life-threatening dengue hemorrhagic fever/dengue shock
      syndrome. We previously reported that a host cellular alpha-glucosidases I and II
      inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in
      cultured cells, and significantly reduced viremia in dengue virus infected AG129
      mice. In this report we show that CM-10-18 also significantly protects mice from
      death and/or disease progress in two mouse models of lethal dengue virus
      infection. Our results thus provide a strong support for the development of CM-10
      18 or its derivatives as antiviral agents to treat servere dengue virus
      infections.

PMID- 21854809
TI  - Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly
      pathogenic avian influenza virus in vitro and in vivo.
AB  - The emergence of the 2009 H1N1 pandemic swine influenza A virus is a good example
      of how this viral infection can impact health systems around the world in a very
      short time. The continuous zoonotic circulation and reassortment potential of
      influenza A viruses (IAV) in nature represents an enormous public health threat
      to humans. Beside vaccination antivirals are needed to efficiently control
      spreading of the disease. In the present work we investigated whether the MEK
      inhibitor U0126, targeting the intracellular Raf/MEK/ERK signaling pathway, is
      able to suppress propagation of the 2009 pandemic IV H1N1v (v=variant) as well as
      highly pathogenic avian influenza viruses (HPAIV) in cell culture and also in
      vivo in the mouse lung. U0126 showed antiviral activity in cell culture against
      all tested IAV strains including oseltamivir resistant variants. Furthermore, we
      were able to demonstrate that treatment of mice with U0126 via the aerosol route
      led to (i) inhibition of MEK activation in the lung (ii) reduction of progeny IAV
      titers compared to untreated controls (iii) protection of IAV infected mice
      against a 100* lethal viral challenge. Moreover, no adverse effects of U0126 were
      found in cell culture or in the mouse. Thus, we conclude that U0126, by
      inhibiting the cellular target MEK, has an antiviral potential not only in vitro
      in cell culture, but also in vivo in the mouse model.

PMID- 21854811
TI  - Zenk expression in auditory regions changes with breeding condition in male Black
      capped chickadees (Poecile atricapillus).
AB  - Black-capped chickadees (Poecile atricapillus) produce different vocalizations at
      different times of year: the fee-bee song is produced by males primarily in
      spring, whereas the chick-a-dee call is produced year-round but most frequently
      in the fall and winter. We wanted to determine if neural response to playback in
      auditory regions of the songbird brain varied with season in parallel to
      production. We captured adult male black-capped chickadees from the wild in
      either breeding condition or non-breeding condition and within 24-48 h of
      bringing them into the laboratory setting, played them recordings of either
      conspecific vocalizations (fee-bee songs or chick-a-dee calls), heterospecific
      vocalizations (Song Sparrow, Melospiza melodia, song), or silence. We then
      measured ZENK protein immunoreactivity (Zenk-ir) in caudomedial nidopallium (NCM)
      and caudomedial mesopallium (CMM), two regions important for perception of
      conspecific vocalizations. We found that, overall, non-breeding birds had greater
      Zenk-ir than breeding birds. In addition, we found that birds in non-breeding
      condition had significantly greater Zenk-ir to heterospecific song than birds in
      breeding condition, but this difference was not seen in birds that heard
      conspecific songs or calls. Finally, in NCMd chickadees had greater response to
      playback of conspecific vocalizations (when combining song and call groups) than
      playback of heterospecific vocalizations but only while in breeding condition.
      Our results qualify the claim that Zenk-ir is biased toward conspecific
      vocalizations, and indicate that specificity of neural response varies with
      season. Variation could be a result of increased production and perceptual demand
      in spring, or hormonal changes in breeding birds, possibly because chickadees
      display vocal plasticity in chick-a-dee calls in the fall, requiring a degree of
      neural plasticity across seasons.

PMID- 21854810
TI  - Threshold of adulthood for the onset of nicotine self-administration in male and
      female rats.
AB  - The great majority of tobacco addiction begins during adolescence. More heavily
      addicted smokers begin smoking earlier, but differentiating the neurobehavioral
      impact of nicotine self-administration during adolescence from self-selection
      bias (whereby people more prone to heavy addiction also begin earlier) cannot be
      ethically unconfounded in humans. The goals of this research were to determine
      the age threshold for the adult-like nicotine self-administration and determine
      sex differences. Male and female Sprague-Dawley rats were tested for nicotine
      self-administration starting at 4, 5, 6, 7, and 8 weeks of age in an operant FR1
      schedule for IV nicotine (0.03 mg/kg/infusion) in 45-min sessions for 2 weeks,
      with 1 week of enforced abstinence and 1 week of resumed access. This study
      replicated our earlier work that nicotine self-administration was increased in
      adolescent vs. adult rats and that the effect was more pronounced in adolescent
      males, but the increased nicotine self-administration was more persistent in
      adolescent-onset females. The age threshold for adult-like behavior was 6-7 weeks
      of age. Adolescent-onset nicotine self-administration had persisting effects of
      eggaurated increases of nicotine self-administration when fixed-ratio
      requirements for self-administration were lowered. Female rats that had begun
      nicotine self-administration during adolescence showed exaggerated increases in
      nicotine self-administration after a switch back to FR1 from FR8, indicating a
      lessened control over their self-administration. Adolescent-onset nicotine self
      administration was not found to potentiate cocaine self-administration.
      Adolescent-onset nicotine self-administration causes persistent increases in
      nicotine self-administration in female rats even after they reach adulthood and
      disrupts control over self-administration behavior.

PMID- 21854812
TI  - Changes in cyclic nucleotides, locomotory behavior, and body length produced by
      novel endogenous neuropeptides in the parasitic nematode Ascaris suum.
AB  - Recent technical advances have rapidly advanced the discovery of novel peptides,
      as well as the transcripts that encode them, in the parasitic nematode Ascaris
      suum. Here we report that many of these novel peptides produce profound and
      varied effects on locomotory behavior and levels of cyclic nucleotides in A.
      suum. We investigated the effects of 31 endogenous neuropeptides encoded by
      transcripts afp-1, afp-2, afp-4, afp-6, afp-7, and afp-9-14 (afp: Ascaris
      FMRFamide-like Precursor protein) on cyclic nucleotide levels, body length and
      locomotory behavior. Worms were induced to generate anteriorly propagating
      waveforms, peptides were injected into the pseudocoelomic cavity, and changes in
      the specific activity (nmol/mg protein) of second messengers cAMP (3'5' cyclic
      adenosine monophosphate) and cGMP (3'5' cyclic guanosine monophosphate) were
      determined. Many of these neuropeptides changed the levels of cAMP (both
      increases and decreases were found), whereas few neuropeptides changed the level
      of cGMP. A subset of the peptides that lowered cAMP was investigated for effects
      on the locomotory waveform and on body length. Injection of AF19, or AF34 (afp
      13), AF9 (afp-14), AF26 or AF41 (afp-11) caused immediate paralysis and cessation
      of propagating body waveforms. These neuropeptides also significantly increased
      body length. In contrast, injection of AF15 (afp-9) reduced the body length, and
      decreased the amplitude of waves in the body waveform. AF30 (afp-10) produced
      worms with tight ventral coils. Although injection of neuropeptides encoded by
      afp-1 (AF3, AF4, AF10 or AF13) produced an increased number of exaggerated body
      waves, there were no effects on either cAMP or cGMP. By injecting peptides into
      behaving A. suum, we have provided an initial screen of the effects of novel
      peptides on several behavioral and biochemical parameters.

PMID- 21854813
TI  - Isoforms of Pax5 and co-regulation of T- and B-cells associated genes influence
      phenotypic traits of ascetic cells causing Dalton's lymphoma.
AB  - The Pax5 and its isoforms influence proliferation of B- and T-cells, during
      development and oncogenesis but molecular mechanism and host-tumor relationship
      is not clear. This report describes status of Pax5 isoforms and co-regulation of
      molecular markers of ascite cells causing Dalton's lymphoma in murine. Higher
      expressions of Pax5, CD19, CD3, Ras and Raf were observed in DLA cells. The
      levels of transcripts as well as p53 protein were also higher in DLA cells. The
      transcript of p53 from DLA cells was a variant of p53 having deletion of 50bp as
      compared to control. On annotation, it reflects transformation related protein
      p53 pseudogene mRNA. Lower level of superoxide dismutase (SOD) indicates
      oxidative stress and higher level of LDH5 in DLA cells reflects hypoxia in
      cancerous condition. The expression of Pax5d/e isoforms in DLA cells suggests
      presence of resting B-cells. Thus, isoforms of Pax5 and co-regulation of T- and B
      cells associated genes influence phenotypic traits of ascetic cells causing
      Dalton's lymphoma.

PMID- 21854814
TI  - Relationship of serum serotonin and salivary cortisol with sensation seeking.
AB  - The present study was conducted to investigate the possible relationship of serum
      serotonin and salivary cortisol with the sensation seeking (SS) trait. Blood and
      saliva samples were taken from 57 male volunteers (mean age 23+/-5years) to
      measure serum serotonin and salivary cortisol concentrations. Zuckerman's
      Sensation Seeking Scale (SSS-V) was used to assess SS. Pearson's correlation
      coefficient revealed that high serum serotonin levels did not correlate
      significantly with low SS scores (r=0.12). However, a negative correlation
      between SS scores and salivary cortisol levels (r=-0.34, p<0.01) was significant,
      suggesting that high SS scores are related to low concentrations of salivary
      cortisol. The negative correlation between salivary cortisol and SS is clearly
      compatible with the optimal level of Catecholamine system activity (CSA),
      component of SS theory, indicating that high sensation seekers (HSSers) tend to
      seek excitement and novelty to compensate for the shortage of CSA achieving
      optimal arousal. Further investigation is needed before conclusions can be drawn
      regarding the relationship of serum serotonin and SS.

PMID- 21854815
TI  - Frontal-parietal responses to "oddball" stimuli depicting "fattened" faces are
      increased in successful dieters: an electroencephalographic study.
AB  - Here we tested the hypothesis that compared with normal weight non dieting
      (control) subjects, normal weight successful dieters submitted to a rigorous and
      continuous monitoring of body weight (i.e. karate athletes) are characterized by
      an increase of cortical responses to oddball visual stimuli depicting the
      enlargement of faces or foods, as neural underpinning of attention processes
      related to the control of weight and eating. Electroencephalographic (EEG) data
      were recorded in 18 successful dieters (5 females) and 24 non dieting subjects (9
      females). The subjects were given frequent (70%) and rare (30%) stimuli depicting
      faces (FACE), food (FOOD), and landscapes (CONTROL). The task was to click the
      mouse after the rare stimuli. The rare stimuli depicted the frequent stimuli
      graphically dilated by 25% along the horizontal axis. Cortical responses
      accompanying attention processes were probed by the difference between positive
      event-related potentials peaking around 400-500ms post-stimulus for the rare
      minus frequent stimuli (P300). The popular freeware LORETA estimated P300
      cortical sources. The results showed that in the FACE condition, the amplitude of
      left frontal (BA 6) and medial parietal (BA 5) P300 sources was higher in the
      successful dieters (karate athletes) than non dieting subjects. These results
      disclose that frontal-parietal responses to "oddball" stimuli depicting enlarged
      faces (i.e. representing face fattening) are enhanced in successful dieters
      (karate athletes). Future studies should evaluate this effect in other
      populations of successful dieters (i.e. boxers, top models etc.).

PMID- 21854816
TI  - Laboratory evolution of an epoxide hydrolase - towards an enantioconvergent
      biocatalyst.
AB  - We performed a laboratory evolution study with the epoxide hydrolase from
      Aspergillus niger M200. This enzyme exhibits no enantioconvergence with the
      substrates styrene oxide or para-chlorostyrene oxide, i.e. racemic vicinal diols
      are produced from the racemic substrates. After saturation mutagenesis, screening
      by chiral gas chromatography revealed enzyme variants with improved
      enantioconvergence as manifested by an increased enantiomeric excess of the diol
      product. Nine amino acid exchanges accumulated in the active site and the
      substrate access tunnel over the course of 5 productive rounds of iterative
      saturation mutagenesis, resulting in an enantioconvergent epoxide hydrolase
      variant. The final mutant enzyme transformed racemic styrene oxide and para
      chlorostyrene oxide to (R)-diol enantiomers with enantiomeric excesses of 70%.
      Sequential bi-enzymatic reactions using the wild-type EH and/or its evolved
      variants enabled preparation of the chiral building blocks (R)-phenyl-1,2
      ethanediol and (R)-para-chlorophenyl-1,2-ethanediol from inexpensive racemic
      epoxides with enantiomeric excesses of 91% and 88%, respectively.

PMID- 21854817
TI  - Intima-media thickness of carotid artery in patients with Behcet's disease.
AB  - BACKGROUND AND AIMS: In this study we investigated the carotid intima-media
      thickness (cIMT) in Tunisian patients with Behcet's disease (BD), and we
      evaluated the relationship between traditional and nontraditional cardiovascular
      risk factors, disease manifestations, disease severity, use of immunosuppressive
      agents and cIMT in patients with BD. METHODS: Fifty patients with BD were
      individually matched to 50 control subjects on the basis of age, gender and
      traditional cardiovascular risk factors. Subjects with diabetes mellitus,
      evidence of myocardial infarction or cerebrovascular disease were excluded from
      the study. Patients with arterial involvement were also excluded. We measured
      serum high-sensitivity C-reactive protein (hsCRP), fibrinogen, creatinine levels
      and lipid profile. We also measured serum vitamin B12, folate, total plasma
      homocysteine levels, and HOMA-IR values. We used B-mode ultrasonography to assess
      the cIMT. RESULTS: cIMT in the BD group was significantly higher than in the
      control group (0.658 +/- 0.112 mm vs. 0.581 +/- 0.087 mm, respectively, p <10(
      3)). The frequency of plaques in the carotid arteries was similar between study
      groups. In univariate analyses, the cIMT of BD patients was correlated with age
      (r = 0.510, p <10(-3)), male gender (p = 0.032), and creatinine clearance (r = 
      0.421, p = 0.003). It was inversely correlated with HOMA-IR values and serum
      vitamin B12 level. cIMT values were independent of disease manifestations,
      disease duration, or corticoid therapy. In the multivariate analysis, only male
      gender and creatinine clearance remained significantly associated with cIMT.
      CONCLUSIONS: Our data indicate morphologic evidence of subclinical
      atherosclerosis in patients with BD. Increased arterial wall thickness was not
      associated with the disease duration, clinical manifestations and
      immunosuppressive therapy.

PMID- 21854818
TI  - Osteoblastogenesis and adipogenesis are higher in osteoarthritic than in
      osteoporotic bone tissue.
AB  - BACKGROUND AND AIMS: New data show that increased adipogenesis in bone marrow may
      decrease osteoblastogenesis, resulting in osteoporosis (OP). Runt-related
      transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor
      gamma (PPARgamma) are two main transcriptional regulators controlling
      osteoblastogenesis and adipogenesis from the same precursor cell in bone-the
      mesenchymal stem cell. Because osteoarthritis (OA) and OP present the opposing
      bone phenotype, our aim was to determine whether the expression of selected
      adipogenic genes is lower in OA compared to OP bone tissue. METHODS: Bone samples
      were obtained from gender-matched OP (n = 54) and OA (n = 49) patients undergoing
      hip arthroplasty. Osteoblastogenesis and adipogenesis were estimated by gene
      expression analysis of RUNX2, PPARgamma2 and their downstream genes. RESULTS: In
      OA bone, significantly higher expression of PPARgamma2 and adiponectin as well as
      RUNX2, osterix and osteocalcin were obtained, suggesting higher adipogenesis and
      osteoblastogenesis in OA than in OP. There were no differences in
      RUNX2/PPARgamma2 and osteocalcin/adiponectin ratios between groups, suggesting
      similar balance of both processes. Higher perilipin 2, angiopoietin-like 4 and
      fatty-acid binding protein 4 mRNA levels in OP suggest activation of other
      transcription factors or hypoxic conditions in OP bone. CONCLUSIONS: Regulation
      of bone formation by RUNX2 and PPARgamma2 is modified in OA compared to OP,
      resulting in higher osteoblastogenesis and adipogenesis in OA. Both processes are
      similarly balanced in OP and OA but less active in OP.

PMID- 21854819
TI  - Insulin-induced neurite-like process outgrowth: acceleration of tau protein
      synthesis via a phosphoinositide 3-kinase~mammalian target of rapamycin pathway.
AB  - Both insulin and tau, promoting neuronal differentiation (neurite outgrowth,
      neuronal polarity, and myelination) and cell survival, are associated with
      neurodegenerative disease (e.g., Alzheimer's disease). The aim of this study was
      to explore relation between insulin-induced activation of insulin signal and
      expression of tau protein on neurite-like process outgrowth in adrenal chromaffin
      cells. Primary cultured bovine adrenal chromaffin cells were incubated with
      insulin to determine whether stimulant of insulin signal could affect tau
      expression and neurite-like process outgrowth. Chronic treatment with insulin
      (?6h) led neurite-like process outgrowth as well as increased tau protein level
      by ~99% in a concentration (EC(50) 5.5nM)- and time-dependent manner, without
      changing Ser(396)-phosphorylated tau level. The insulin-induced increase of tau
      protein level was abolished by LY294002 [an inhibitor of phosphoinositide 3
      kinase (PI3K)] and rapamycin [an inhibitor of mammalian target of rapamycin
      (mTOR)], but not by PD98059 and U0126 [two inhibitors of mitogen-activated
      protein kinase/extracellular signal-regulated kinase (MEK)]. Additionally,
      insulin-induced increase of tau was blocked by cyclohexamide (an inhibitor of
      protein synthesis), but not by actinomycin D (an inhibitor of gene
      transcription). Pulse-label followed by polyacrylamide gel electrophoresis
      revealed that insulin accelerated tau protein synthesis rate (t(1/2)) from 2.6 to
      1.9h. Insulin did not change tau mRNA level. Taken together, these results
      suggest that insulin-induced activation of PI3K~mTOR pathway up-regulated tau
      protein via acceleration of protein synthesis, on which insulin promoted neurite
      like process outgrowth.

PMID- 21854820
TI  - 2-(Cyclohexylamino)-1-(4-cyclopentylpiperazin-1-yl)-2-methylpropan-1-one, a novel
      compound with neuroprotective and neurotrophic effects in vitro.
AB  - Focusing on development of novel drug candidates for the treatment of
      neurodegenerative diseases, we developed and synthesized a new compound, 2
      (cyclohexylamino)-1-(4-cyclopentylpiperazin-1-yl)-2-methylpropan-1-one (amido
      piperizine 1). The compound demonstrated robust neuroprotective properties after
      both glutamate excitotoxicity and peroxide induced oxidative stress in primary
      cortical cultures. Furthermore, amido-piperizine 1 was found to significantly
      induce neurite outgrowth in vitro which could suggest central reparative and
      regenerative potential of the compound. With these potential beneficial effects
      in CNS, the ability of the amido-piperizine 1 to penetrate the blood-brain
      barrier was tested using MDR1-MDCK cells. Amido-piperizine 1 was found not to be
      a P-gp substrate and to have a high blood-brain barrier penetration potential,
      indicating excellent availability to the CNS. Moreover, amido-piperizine 1 had a
      fast metabolic clearance rate in vitro, suggesting that parenteral in vivo
      administration seems preferable. As an attempt to elucidate a possible mechanism
      of action, we found that amido-piperizine 1 bound in nano-molar range to the
      sigma-1 receptor, which could explain the observed neuroprotective and
      neurotrophic properties, and with a 100-fold lower affinity to the sigma-2
      receptor. These results propose that amido-piperizine 1 may hold promise as a
      drug candidate for the treatment of stroke/traumatic brain injury or other
      neurodegenerative diseases.

PMID- 21854821
TI  - Neuropathology of vaccination in infants and children.
AB  - AIMS: Documentation of clinical-pathological features of 37 infants/children
      whose parents alleged a relationship between vaccination and death or permanent
      central nervous system (CNS) damage, and sought compensation through the National
      Vaccine Injury Compensation Program. SCOPE: Of the 5545 claims filed during the
      10-year period (1990-1999), CNS tissue was available for evaluation by a
      pediatric neuropathologist in 37; 33 died and 4 had a biopsy or lobectomy. Most
      commonly implicated vaccines were DTP/DTaP, followed by MMR and IPV/OPV, but
      almost all of the vaccines currently given to infants/children were alleged to be
      responsible for the illness/death. No lesions were found in 5 of 37 (13.5%). The
      most frequent abnormality consisted of acute anoxic encephalopathy (14 of 37 -
      37.8%), consequent to several different causes, such as positional asphyxia,
      cardio-respiratory arrest during status epilepticus, etc. The remaining children
      manifested other lesions, including inflammation (5 of 37 - 13.5%), vascular and
      developmental anomalies (4 each of 37 or 10.6%), cerebral edema and system
      degeneration (2 each of 37 or 5.4%), and one case of heavy metal exposure in a
      child living near an abandoned mine (2.2%). CONCLUSIONS: There was no obvious
      relationship between type of vaccine (or vaccines simultaneously administered) to
      time of onset of symptoms, nature of symptoms or the lesions found.

PMID- 21854822
TI  - Live vaccine of viral hemorrhagic septicemia virus (VHSV) for Japanese flounder
      at fish rearing temperature of 21 degrees C instead of Poly(I:C) administration.
AB  - The process of "Poly(I:C) immunization" involves immunization of fish with a
      pathogenic live virus, followed by administration of Poly(I:C), which induces a
      transient, non-specific antiviral state. As a result, fish in an antiviral state
      survive the initial immunization with live virus. Moreover, these fish are able
      to mount a specific protective immune response against the injected pathogenic
      virus. In the present study, we investigated the optimum temperature for
      Poly(I:C) immunization of Japanese flounder Paralichthys olivaceus with live
      viral hemorrhagic septicemia virus (VHSV). It was revealed that the optimum
      temperature was around at 17 degrees C for Poly(I:C) immunization in Japanese
      flounder. Furthermore, the protection efficacy of Poly(I:C) immunization was
      significantly decreased by elevation of fish rearing temperature, and no efficacy
      was observed at a fish rearing temperature of 25 degrees C. Interestingly, no
      mortality by VHSV infection was observed in fish reared at 21 degrees C and 25
      degrees C even when those fish were not administered Poly(I:C). All of the
      survivors from the first VHSV-challenge at 21 degrees C were strongly protected
      from re-challenge with VHSV. However, almost all of the survivors (>=82.6%) from
      the first challenge at 25 degrees C were lost by the second challenge with VHSV.
      It was thus concluded that by rearing fish at 21 degrees C and challenging with
      live VHSV, it is possible to induce strong specific immunity in Japanese flounder
      without Poly(I:C) administration.

PMID- 21854823
TI  - Norovirus VLPs and rotavirus VP6 protein as combined vaccine for childhood
      gastroenteritis.
AB  - Noroviruses (NoVs) and rotaviruses (RVs) are the two most important viral causes
      of severe gastroenteritis in young children worldwide. Live oral RV vaccines are
      already part of routine childhood immunization in many countries, but may be
      associated with low risk of intussusception and other potential risks associated
      with live vaccines. NoV capsid-derived virus-like particles (VLPs) are in early
      phase clinical trials, but there is no vaccine available yet. We suggest that
      there is a need for non-live vaccines against both enteric pathogens. We have
      combined NoV GII-4 VLPs and human RV recombinant VP6 (rVP6) protein produced by
      recombinant baculovirus (BV) expression system in insect cells and used this
      combination vaccine to immunize BALB/c mice parenterally. Strong systemic cross
      reactive and cross-blocking antibody responses towards NoV and RV were induced,
      and there was no interference of the immune response to either antigen given in
      combination. Rather, we observed an adjuvant effect of rVP6 on the NoV-specific
      homologous and heterologous immune responses to genotypes not included in a
      vaccine formulation.

PMID- 21854824
TI  - Efficacy of a vaccine that links viral epitopes to flagellin in protecting aged
      mice from influenza viral infection.
AB  - Influenza vaccines are less effective in older people than younger people. This
      impaired ability to protect older people from influenza viral lung infection has
      important implications as older people suffer a higher morbidity and mortality
      from influenza viral lung infection than younger people. Therefore, the
      development of novel effective vaccines that induce protection from influenza
      viral infections in older people are urgently needed. We had previously shown
      that direct linking the TLR5 activator, flagellin, to viral peptides induces
      effective immunity to viral antigens in young mice and people, respectively. In
      this study, we tested the efficacy of this vaccine platform with the
      hemagglutinin peptide of the influenza A strain virus (vaccine denoted as
      STF2.HA1-2) in protecting aged mice from subsequent influenza viral lung
      infection. We found that a 3.0 MUg dose of the vaccine was effective in reducing
      mortality and increasing clinical well-being during influenza viral lung
      infection in aged mice. However, this effect was inferior to the response induced
      in young mice. Defects in the adaptive immune system but not the innate immune
      system were associated with this reduced effectiveness of the vaccine with aging.
      Our results indicate that the STF2.HA1-2 vaccine is effective in protecting aged
      hosts from influenza lung infection, although defects in the adaptive immune
      system with aging may limit the effectiveness of this vaccine in older people.

PMID- 21854825
TI  - Cost-effectiveness of the introduction of the pneumococcal polysaccharide vaccine
      in elderly Colombian population.
AB  - BACKGROUND: Streptococcus pneumoniae causes community-acquired pneumonia, otitis
      media and meningitis, with higher incidences at the extremes of life. PPV-23
      vaccine is widely used in prevention of pneumonia and invasive pneumococcal
      disease in older adults in developed countries. We developed an evaluation of
      cost-effectiveness of implementing PPV-23 in Colombian population over 60 years.
      METHODS: The number of cases of pneumonia and meningitis in patients over 60
      years and the proportion by S. pneumoniae was estimated based on a review of
      literature. A decision tree model with a 5-year time horizon was built to
      evaluate the cost-effectiveness of the implementation of the PPV-23 in this
      population. Direct health care costs of out- and in-patients were calculated
      based on expenditure records from the Bogota public health system. Incremental
      cost-effectiveness ratios per life saved and per year of life gained were
      estimated based on the decision tree model. Deterministic and probabilistic
      sensitivity analyses were performed. RESULTS: Without vaccination 4460 (range
      2384-8162) bacteremic pneumococcal pneumonias and 141 (range 73-183) pneumococcal
      meningitis would occur among people over 60 years old in Colombia. In the first
      year, vaccination with PPV-23 at US$8/dose would save 480 (range 100-1753) deaths
      due to Invasive and non-invasive pneumococcal disease. Vaccination would results
      in US$3400/deaths averted (range US$1028-10,862) and US$1514/life years gained
      (range US$408-5404). CONCLUSION: Vaccination with PPV-23 in over 60 years is a
      highly cost-effective public health measure in Colombia. Despite some
      limitations, the results are robust, and may help developing countries to perform
      informed decisions about the introduction of the vaccine.

PMID- 21854826
TI  - Correlation of tissue concentrations of the pyrethroid bifenthrin with
      neurotoxicity in the rat.
AB  - The potential for human exposure to pyrethroid pesticides has prompted
      pharmacodynamic and pharmacokinetic research to better characterize risk. This
      work tested the hypothesis that blood and brain concentrations of the pyrethroid
      bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats
      received a single oral dose of bifenthrin dissolved in corn oil. Using figure
      eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure
      to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and
      brains were collected immediately following motor activity assays. Bifenthrin
      concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin
      exposure decreased motor activity from 20% to 70% in a dose-dependent manner at
      both time points. The relationship between motor activity data and administered
      dose, and blood and brain bifenthrin concentrations were described using a
      sigmoidal E(max) model. The relationships between motor activity and administered
      dose or blood concentrations were different between the 4- and 7-h time points.
      The relationship between motor activity and brain concentration was not
      significantly different between the two time points. These data suggest that
      momentary brain concentration of bifenthrin may be a more precise dose metric for
      predicting behavioral effects because the relationship between brain
      concentration and locomotor activity is independent of the time of exposure.

PMID- 21854827
TI  - Genistein induces breast cancer-associated aromatase and stimulates estrogen
      dependent tumor cell growth in in vitro breast cancer model.
AB  - In breast cancer, the interaction between estrogen-producing breast adipose
      fibroblasts (BAFs) and estrogen-dependent epithelial tumor cells is pivotal.
      Local estrogen production is catalyzed by aromatase, which is differentially
      regulated in disease-free and tumorigenic breast tissue. The use of aromatase
      inhibitors to block local estrogen production has proven effective in treatment
      of estrogen-dependent breast cancer. However, a major problem during breast
      cancer treatment is the sudden onset of menopause and many women seek for
      alternative medicines, such as the soy isoflavone genistein. In this study, we
      show that genistein can induce estrogen-dependent MCF-7 tumor cell growth and
      increase breast cancer-associated aromatase expression and activity in vitro. We
      have previously developed an in vitro breast cancer model where the positive
      feedback loop between primary BAFs and estrogen-dependent MCF-7 tumor cells is
      operational, thereby representing a more natural in vitro model for breast
      cancer. In this model, genistein could negate the growth inhibitory action of the
      aromatase inhibitor fadrozole at physiologically relevant concentrations. These
      data suggest that soy-based supplements might affect the efficacy of breast
      cancer treatment with aromatase inhibitors. Considering the high number of breast
      cancer patients using soy supplements to treat menopausal symptoms, the
      increasing risk for adverse interactions with breast cancer treatment is of major
      concern and should be considered with care.

PMID- 21854828
TI  - The stability of intramolecular DNA G-quadruplexes compared with other
      macromolecules.
AB  - DNA quadruplexes are often conceived as very stable structures. However, most of
      the free energy of stabilization derives from specific ion binding via inner
      sphere coordination of the GO6 of the guanine residues comprising the basic
      quartet. When compared with other nucleic acid structures such as DNA or RNA
      duplexes and hairpins, or proteins of the same number of atoms, metal-coordinated
      intramolecular quadruplexes are found to be of comparable or lower thermodynamic
      stability under similar solution conditions. Furthermore, intramolecular
      quadruplexes are actually less stable kinetically, than DNA duplexes or hairpins
      of the same size. Although the literature is incomplete, it is clear that
      polyelectrolyte ion effects, the influence of solvation and steric crowding on
      stability are qualitatively different between intramolecular quadruplexes and DNA
      duplexes. For example, decreasing water activity destabilizes DNA duplexes,
      whereas quadruplexes are stabilized. The variety of folded conformations
      accessible to a single sequence further implies strong sensitivity of the
      conformational ensemble to the solution conditions, compared with DNA duplexes or
      small single domain proteins. These considerations may have relevance to the
      conditions prevailing inside cell nuclei and therefore the structures that
      potentially might form in vivo.

PMID- 21854829
TI  - Biomarkers for major depression and its delineation from neurodegenerative
      disorders.
AB  - Major depressive disorders (MDD) are among the most debilitating diseases
      worldwide and occur with a high prevalence in elderly individuals.
      Neurodegenerative diseases (in particular Alzheimer's disease, AD) do also show a
      strong age-dependent increase in incidence and prevalence among the elderly
      population. A high number of geriatric patients with MDD show cognitive deficits
      and a very high proportion of AD patients present co-morbid MDD, which poses
      difficult diagnostic and prognostic questions. Especially in prodromal and in
      very early stages of AD, it is almost impossible to differentiate between pure
      MDD and MDD with underlying AD. Here, we give a comprehensive review of the
      literature on the current state of candidate biomarkers for MDD ("positive MDD
      markers") and briefly refer to established and validated diagnostic AD biomarkers
      in order to rule out underlying AD pathophysiology in elderly MDD subjects with
      cognitive impairments ("negative MDD biomarkers"). In summary, to date there is
      no evidence for positive diagnostic MDD biomarkers and the only way to delineate
      MDD from AD is to use "negative MDD" biomarkers. Because of this highly
      unsatisfactory current state of MDD biomarker research, we propose a research
      strategy targeting to detect and validate positive MDD biomarkers, which is based
      on a complex (genetic, molecular and neurophysiological) biological model that
      incorporates current state of the art knowledge on the pathobiology of MDD. This
      model delineates common pathways and the intersection between AD and MDD.
      Applying these concepts to MDD gives hope that positive MDD biomarkers can be
      successfully identified in the near future.

PMID- 21854830
TI  - Neural regulation of intestinal nutrient absorption.
AB  - The nervous system and the gastrointestinal (GI) tract share several common
      features including reciprocal interconnections and several neurotransmitters and
      peptides known as gut peptides, neuropeptides or hormones. The processes of
      digestion, secretion of digestive enzymes and then absorption are regulated by
      the neuro-endocrine system. Luminal glucose enhances its own absorption through a
      neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres.
      Absorbed glucose stimulates insulin release that activates hepatoenteric neural
      pathways leading to an increase in the expression of glucose transporters.
      Adrenergic innervation increases glucose absorption through alpha1 and beta
      receptors and decreases absorption through activation of alpha2 receptors. The
      vagus nerve plays an important role in the regulation of diurnal variation in
      transporter expression and in anticipation to food intake. Vagal CSPAs exert
      tonic inhibitory effects on amino acid absorption. It also plays an important
      role in the mediation of the inhibitory effect of intestinal amino acids on their
      own absorption at the level of proximal or distal segment. However, chronic
      extrinsic denervation leads to a decrease in intestinal amino acid absorption.
      Conversely, adrenergic agonists as well as activation of CSPA fibres enhance
      peptides uptake through the peptide transporter PEPT1. Finally, intestinal
      innervation plays a minimal role in the absorption of fat digestion products.
      Intestinal absorption of nutrients is a basic vital mechanism that depends
      essentially on the function of intestinal mucosa. However, intrinsic and
      extrinsic neural mechanisms that rely on several redundant loops are involved in
      immediate and long-term control of the outcome of intestinal function.

PMID- 21854832
TI  - Partial restoration of the long QT syndrome associated KCNQ1 A341V mutant by the
      KCNE1 beta-subunit.
AB  - BACKGROUND: The A341V mutation in the pore-forming KCNQ1 subunit of the slowly
      activating delayed-rectifier potassium current (IKs) underlies a common form of
      the long QT syndrome, and is associated with an unusually severe phenotype.
      However, there is controversy regarding the underlying mechanism responsible for
      the clinically observed phenotype. We investigated the biophysical
      characteristics of A341V in a cardiac environment by utilizing a cardiac cell
      line, and in particular the impact of the KCNE1 beta-subunit. METHODS: Whole-cell
      current were recorded from transiently transfected HL-1 cells, a cardiac cell
      line. Mutant KCNQ1 and KCNE1 were constructed by site-directed mutagenesis.
      RESULTS: The A341V mutant resulted in a non-functional channel when expressed
      alone. When co-expressed with wild type KCNE1, A341V produced a slowly activating
      current, with a smaller current density, slower rates of activation, and a
      depolarized shift in its activation curve compared to the wild type KCNQ1+KCNE1.
      Confocal microscopy confirmed the surface expression of GFP-tagged A341V,
      suggesting a functionally defective protein. A T58A mutation in KCNE1 abolished
      functional restoration of A341V. Under heterozygous conditions, the expression of
      A341V+KCNQ1+KCNE1 reduced but did not abolish the electrophysiological changes
      observed in A341V+KCNE1. A dominant negative effect of A341V was also observed.
      Action potential simulations revealed that the A341V mutation is arrhythmogenic.
      CONCLUSIONS: The KCNE1 beta-subunit partially rescued the non-functional A341V
      mutant, with electrophysiological properties distinct from the wild type IKs.
      GENERAL SIGNIFICANCE: The severity of the A341V phenotype may be due to a
      combination of a significant suppression of the IKs with altered biophysical
      characteristics.

PMID- 21854831
TI  - Animal models of human mitochondrial DNA mutations.
AB  - BACKGROUND: Mutations in mitochondrial DNA (mtDNA) cause a variety of pathologic
      states in human patients. Development of animal models harboring mtDNA mutations
      is crucial to elucidating pathways of disease and as models for preclinical
      assessment of therapeutic interventions. SCOPE OF REVIEW: This review covers the
      knowledge gained through animal models of mtDNA mutations and the strategies used
      to produce them. Animals derived from spontaneous mtDNA mutations, somatic cell
      nuclear transfer (SCNT), nuclear translocation of mitochondrial genes followed by
      mitochondrial protein targeting (allotopic expression), mutations in
      mitochondrial DNA polymerase gamma, direct microinjection of exogenous
      mitochondria, and cytoplasmic hybrid (cybrid) embryonic stem cells (ES cells)
      containing exogenous mitochondria (transmitochondrial cells) are considered.
      MAJOR CONCLUSIONS: A wide range of strategies have been developed and utilized in
      attempts to mimic human mtDNA mutation in animal models. Use of these animals in
      research studies has shed light on mechanisms of pathogenesis in mitochondrial
      disorders, yet methods for engineering specific mtDNA sequences are still in
      development. GENERAL SIGNIFICANCE: Research animals containing mtDNA mutations
      are important for studies of the mechanisms of mitochondrial disease and are
      useful for the development of clinical therapies. This article is part of a
      Special Issue entitled Biochemistry of Mitochondria.

PMID- 21854833
TI  - Physiological roles of ovotransferrin.
AB  - BACKGROUND: Ovotransferrin is an iron-binding glycoprotein, found in avian egg
      white and in avian serum, belonging to the family of transferrin iron-binding
      glycoproteins. All transferrins show high sequence homology. In mammals are
      presents two different soluble glycoproteins with different functions: i) serum
      transferrin that is present in plasma and committed to iron transport and iron
      delivery to cells and ii) lactoferrin that is present in extracellular fluids and
      in specific granules of polymorphonuclear lymphocytes and committed to the so
      called natural immunity. To the contrary, in birds, ovotransferrin remained the
      only soluble glycoprotein of the transferrin family present both in plasma and
      egg white. SCOPE OF REVIEW: Substantial experimental evidences are summarized,
      illustrating the multiple physiological roles of ovotransferrin in an attempt to
      overcome the common belief that ovotransferrin is a protein dedicated only to
      iron transport and to iron withholding antibacterial activity. MAJOR CONCLUSIONS:
      Similarly to the better known family member protein lactoferrin, ovotransferrin
      appears to be a multi-functional protein with a major role in avian natural
      immunity. GENERAL SIGNIFICANCE: Biotechnological applications of ovotransferrin
      and ovotransferrin-related peptides could be considered in the near future,
      stimulating further research on this remarkable protein. This article is part of
      a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and
      disorders.

PMID- 21854834
TI  - Impaired mitochondrial biogenesis in hippocampi of rats with chronic seizures.
AB  - Mitochondrial dysfunction has been suggested to be a contributing factor of
      epilepsy, but the underlying mechanisms are not completely explored.
      Mitochondrial biogenesis is involved in regulation of mitochondrial content,
      morphology, and function. In the current study, we show mitochondrial biogenesis
      severely impaired in hippocampi of rats with chronic seizures induced by
      pilocarpine, as evidenced by decreased mitochondrial DNA (mtDNA) content and
      decreased mtDNA-encoded protein level. Furthermore, we show mtDNA transcription
      and replication reduced in rats with chronic seizures. These defects were
      independent of downregulation of mitochondrial biogenesis-related factors, such
      as peroxisome proliferator-activated receptor gamma coactivator-1alpha, nuclear
      respiratory factor-1, and mitochondrial transcription factor A (Tfam), but
      depended on reduced Tfam-DNA binding activity. The present study suggests novel
      mechanisms for mitochondrial dysfunction during chronic seizures.

PMID- 21854835
TI  - Pointing to double-step visual stimuli from a standing position: motor
      corrections when the speed-accuracy trade-off is unexpectedly modified in-flight.
      A breakdown of the perception-action coupling.
AB  - The time required to complete a fast and accurate movement is a function of its
      amplitude and the target size. This phenomenon refers to the well known speed
      accuracy trade-off. Some interpretations have suggested that the speed-accuracy
      trade-off is already integrated into the movement planning phase. More
      specifically, pointing movements may be planned to minimize the variance of the
      final hand position. However, goal-directed movements can be altered at any time,
      if for instance, the target location is changed during execution. Thus, one
      possible limitation of these interpretations may be that they underestimate
      feedback processes. To further investigate this hypothesis we designed an
      experiment in which the speed-accuracy trade-off was unexpectedly varied at the
      hand movement onset by modifying separately the target distance or size, or by
      modifying both of them simultaneously. These pointing movements were executed
      from an upright standing position. Our main results showed that the movement time
      increased when there was a change to the size or location of the target. In
      addition, the terminal variability of finger position did not change. In other
      words, it showed that the movement velocity is modulated according to the target
      size and distance during motor programming or during the final approach,
      independently of the final variability of the hand position. It suggests that
      when the speed-accuracy trade-off is unexpectedly modified, terminal feedbacks
      based on intermediate representations of the endpoint velocity are used to
      monitor and control the hand displacement. There is clearly no obvious perception
      action coupling in this case but rather intermediate processing that may be
      involved.

PMID- 21854836
TI  - Effects of increased opportunity for physical exercise and learning experiences
      on recognition memory and brain-derived neurotrophic factor levels in brain and
      serum of rats.
AB  - Studies with animal models showed that cellular, structural, and behavioral
      changes induced by environmental enrichment are related to increased levels of
      brain-derived neurotrophic factor (BDNF) in the brain. These evidence suggest
      that BDNF could be an interesting biomarker of the effects of lifestyle on
      cognition and other behavioral parameters in humans, mainly if the BDNF
      alterations in brain are accompanied by correspondent peripheral modifications,
      since human studies depend basically on the evaluation of this neurotrophin in
      serum or plasma. To test this hypothesis, we analyzed the effects of
      environmental enrichment on long-term memory for object recognition and on BDNF
      levels of hippocampus, frontal cortex, and serum of rats exposed to an
      experimental protocol that could be more easily translated to human intervention
      studies. Animals were maintained for 10 weeks in a social (standard laboratory
      conditions) or enriched (increased opportunity for physical exercise and learning
      experiences) condition. In the 7th week, they were submitted to behavioral
      testing (open field and novel object memory task), and at the end of the 10th
      week, they were killed and BDNF levels were analyzed. Animals maintained in the
      enriched condition showed enhanced performance on the memory task in the absence
      of any significant alteration in central or peripheral BDNF levels. The results
      of this study are important to highlight the need to develop experimental
      protocols using animal models that more closely resemble the characteristics of
      studies with humans and motivate more investigations to determine the conditions
      under which BDNF could be a biomarker of the effects of environment enrichment.

PMID- 21854838
TI  - Genotype-dependent participation of coat color gene loci in the behavioral traits
      of laboratory mice.
AB  - To evaluate if loci responsible for coat color phenotypes contribute to
      behavioral characteristics, we specified novel gene loci associated with social
      exploratory behavior and examined the effects of the frequency of each allele at
      distinct loci on behavioral expression. We used the F2 generation, which arose
      from the mating of F1 mice obtained by interbreeding DBA/2 and ICR mice.
      Phenotypic analysis indicated that the agouti and albino loci affect behavioral
      traits. A genotype-based analysis revealed that novel exploratory activity was
      suppressed in a manner dependent on the frequency of the dominant wild-type
      allele at the agouti, but not albino, locus. The allele-dependent suppression was
      restricted to colored mice and was not seen in albino mice. The present results
      suggest that the agouti locus contributes to a particular behavioral trait in the
      presence of a wild-type allele at the albino locus, which encodes a structural
      gene for tyrosinase.

PMID- 21854837
TI  - Gene expression and behaviour in mouse models of HD.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease,
      resulting in expansion of the CAG repeat in exon 1 of the HTT gene. The resulting
      mutant huntingtin protein has been implicated in the disruption of a variety of
      cellular functions, including transcription. Mouse models of HD have been central
      to the development of our understanding of gene expression changes in this
      disease, and are now beginning to elucidate the relationship between gene
      expression and behaviour. Here, we review current mouse models of HD and their
      characterisation in terms of gene expression. In addition, we look at how this
      can inform behaviours observed in mouse models of disease. The relationship
      between gene expression and behaviour in mouse models of HD is important, as this
      will further our knowledge of disease progression and its underlying molecular
      events, highlight new treatment targets, and potentially provide new biomarkers
      for therapeutic trials.

PMID- 21854839
TI  - Male Wistar rats are more susceptible to lasting social anxiety than Wild-type
      Groningen rats following social defeat stress during adolescence.
AB  - Adolescence is an important period for the development of adult social
      competences. Social stress during adolescence may contribute not only to an
      inadequate social development but also to adult vulnerability to social anxiety.
      There seems to be a clear individual differentiation, however, in the
      vulnerability to the long-term negative consequences of social stress. The
      current study further explores this individual vulnerability and is aimed at the
      influence of social stress during adolescence on adult social anxiety and its
      context specificity. Rats from different strains (Wistar and Wild-type Groningen
      rats) were exposed to the resident-intruder paradigm five times during 10 min
      each in the period between postnatal day 45 and 58. Three and 7 weeks later, the
      animals were re-exposed to the context in the presence of either a dominant male
      or an anestrous female behind a wire mesh screen. Wistar rats that were socially
      defeated spent less time exploring the social stimulus in comparison with
      socially defeated Wild-type rats and their non-defeated controls. We conclude
      that the stressed Wistar rat shows signs of generalized social anxiety indicating
      that the Wistar rat can be considered as a vulnerable phenotype to effects of
      adolescent social stress.

PMID- 21854841
TI  - Foreign protein production using plant cells: opportunities and challenges.

PMID- 21854840
TI  - Cisplatin ototoxicity in rat cochlear organotypic cultures.
AB  - Ototoxicity is a dose-limiting side effect of chemotherapeutic treatment with
      cisplatin. In a series of experiments on neonatal rat cochlear organotypic
      cultures, the extent of damage induced by a broad range of cisplatin treatment
      concentrations was examined. Paradoxically, it was found that hair cell loss was
      greater following 48 h exposure to low (10, 50 and 100 MUM) versus high (400 and
      1000 MUM) concentrations of cisplatin; these findings indicate that hair cells
      possess intrinsic resistance to high levels of extracellular cisplatin. Using
      cisplatin conjugated to Alexa Fluor 488, it was found that cisplatin is readily
      taken up by hair cells at low concentrations, but is largely excluded at high
      concentrations. Recent studies indicate that the major influx of cisplatin into
      hair cells occurs via the copper transporter, Ctr1, whereas ATP7A and ATP7B are
      copper pumps responsible for cisplatin sequestration and efflux. Using
      immunolabeling procedures for these copper trafficking proteins, it was found
      that Ctr1 and ATP7B were localized in the hair cells, whereas ATP7A showed
      extensive labeling in the pillar cells in the organ of Corti. Additional
      experiments confirmed the protective effect of copper sulfate and cimetidine in
      attenuating cisplatin-induced hair cell loss. However, because neither copper
      sulfate nor cimetidine provided complete protection against cisplatin, and high
      levels of copper sulfate itself were found to be ototoxic, it is suggested that
      future therapeutic efforts may benefit from a combination of pharmacological
      treatments which seek to not only limit the uptake of cisplatin into cochlear
      cells but also increase its efflux.

PMID- 21854842
TI  - Sustained CaMKII activity mediates transient oxidative stress-induced long-term
      facilitation of L-type Ca(2+) current in cardiomyocytes.
AB  - Oxidative stress remodels Ca(2+) signaling in cardiomyocytes, which promotes
      altered heart function in various heart diseases. Ca(2+)/calmodulin-dependent
      protein kinase II (CaMKII) was shown to be activated by oxidation, but whether
      and how CaMKII links oxidative stress to pathophysiological long-term changes in
      Ca(2+) signaling remain unknown. Here, we present evidence demonstrating the role
      of CaMKII in transient oxidative stress-induced long-term facilitation (LTF) of L
      type Ca(2+) current (I(Ca,L)) in rat cardiomyocytes. A 5-min exposure of 1mM
      H(2)O(2) induced an increase in I(Ca,L), and this increase was sustained for ~1h.
      The CaMKII inhibitor KN-93 fully reversed H(2)O(2)-induced LTF of I(Ca,L),
      indicating that sustained CaMKII activity underlies this oxidative stress-induced
      memory. Simultaneous inhibition of oxidation and autophosphorylation of CaMKII
      prevented the maintenance of LTF, suggesting that both mechanisms contribute to
      sustained CaMKII activity. We further found that sarcoplasmic reticulum Ca(2+)
      release and mitochondrial ROS generation have critical roles in sustaining CaMKII
      activity via autophosphorylation- and oxidation-dependent mechanisms. Finally, we
      show that long-term remodeling of the cardiac action potential is induced by
      H(2)O(2) via CaMKII. In conclusion, CaMKII and mitochondria confer oxidative
      stress-induced pathological cellular memory that leads to cardiac arrhythmia.

PMID- 21854844
TI  - Gadd45a and Gadd45g regulate neural development and exit from pluripotency in
      Xenopus.
AB  - Gadd45 genes encode a small family of multifunctional stress response proteins,
      mediating cell proliferation, apoptosis, DNA repair and DNA demethylation. Their
      role during embryonic development is incompletely understood. Here we identified
      Xenopus Gadd45b, compared Gadd45a, Gadd45b and Gadd45g expression during Xenopus
      embryogenesis, and characterized their gain and loss of function phenotypes.
      Gadd45a and Gadd45g act redundantly and double Morpholino knock down leads to
      pleiotropic phenotypes, including shortened axes, head defects and
      misgastrulation. In contrast, Gadd45b, which is expressed at very low levels,
      shows little effect upon knock down or overexpression. Gadd45ag double Morphants
      show reduced neural cell proliferation and downregulation of pan-neural and
      neural crest markers. In contrast, Gadd45ag Morphants display increased
      expression of multipotency marker genes including Xenopus oct4 homologs as well
      as gastrula markers, while mesodermal markers are downregulated. The results
      indicate that Gadd45ag are required for early embryonic cells to exit
      pluripotency and enter differentiation.

PMID- 21854843
TI  - Prenatal exposure to bisphenol A and phthalates and infant neurobehavior.
AB  - OBJECTIVE: To examine the association of prenatal exposure to bisphenol A and
      select common phthalates with infant neurobehavior measured at 5 weeks. METHODS:
      We compared the concentration of maternal urinary metabolites of bisphenol A and
      phthalates at two distinct time points in pregnancy (16w, 26w) with scores on the
      NICU Network Neurobehavioral Scale (NNNS) at 5 weeks of age in a cohort of 350
      mother/infant pairs. RESULTS: Prenatal exposure to BPA was not significantly
      associated with neurobehavioral outcomes at 5 weeks. Significant associations
      between prenatal exposure to measured phthalates and infant neurobehavioral
      outcomes differed by type of phthalate and were only seen with exposure measured
      at 26 weeks. Higher total di-butyl phthalate (DBP) metabolites at 26w were
      associated with improved behavioral organization evidenced by decreased arousal
      (p=.04), increased self-regulation (p=.052), and decreased handling (p=.02). In
      males, higher total di-2-ethylhexyl phthalate (DEHP) metabolites at 26w were
      associated with more nonoptimal reflexes (p=.02). CONCLUSION: The association
      between prenatal phthalate exposure and infant neurobehavior differed by type of
      phthalate and was evident only with exposure measured at 26w. Prenatal exposure
      to DBP was associated with improved behavioral organization in 5-week-old
      infants. Prenatal exposure to DEHP was associated with nonoptimal reflexes in
      male infants. There was no evidence of an association between prenatal BPA
      exposure and infant neurobehavior.

PMID- 21854846
TI  - Risk assessment of accidental nortriptyline poisoning: the importance of
      cytochrome P450 for nortriptyline elimination investigated using a population
      based pharmacokinetic simulator.
AB  - It is not possible to make a prospective clinical study that reveals the
      importance of the nortriptyline metabolising cytochrome P450 (CYP) isoforms
      (CYP1A2, CYP2C19, CYP2D6, and CYP3A4) in relation to attaining potential toxic
      nortriptyline concentrations with a possibly fatal outcome. Therefore to study
      this we have applied the population based pharmacokinetic simulator Simcyp. The
      objective was to estimate how important CYP2C19 and CYP2D6 phenotype status,
      hepatic activity of CYP3A4, body weight, CYP2D6 phenotype dose adjustment, and
      drug-drug interactions are with regard to accidental poisoning in a virtual
      population receiving a daily dose of 100mg nortriptyline. Accidental poisoning is
      here defined as intake of a normal dose which because of slow metabolism may lead
      to potentially toxic concentrations. The input parameters values for Simcyp were
      based on average literature in vitro and in vivo data. The Simcyp simulations of
      nortriptyline pharmacokinetics reflected reported clinical concentration-time
      profiles, therapeutic drug monitoring data, and the consequence of CYP2D6 poor
      metaboliser (PM) and ultrarapid metaboliser status. Of the investigated factors,
      the simulations indicate that having CYP2D6 PM status is a major risk factor for
      attaining high concentrations and thereby possibly becoming poisoned by
      nortriptyline. Of the CYP2D6 PM subjects 16% would attain plasma concentrations
      exceeding the toxic limit. Individuals with the combination of CYP2D6 PM status
      and 10% of the average liver CYP3A4 expression had a 90% risk of becoming
      poisoned. The results point towards the combination of low CYP3A4 activity and
      CYP2D6 PM status of major importance for attaining possibly toxic nortriptyline
      concentrations. In a forensic toxicological context, the results indicate that
      both the activity of CYP3A4, information on possible drug-drug interactions, and
      the genotype of CYP2D6 are needed in order to elucidate whether an individual
      might have been accidentally poisoned because of slow metabolism. In a clinical
      context, the simulations suggest that precise individual dose adjustment of
      nortriptyline requires information regarding the activity of both CYP3A4 and
      CYP2D6. This underlines the value of therapeutic drug monitoring for
      nortriptyline. Population based pharmacokinetic simulations are considered useful
      tools for risk assessment in clinical and forensic toxicology.

PMID- 21854845
TI  - Wnt signaling specifies and patterns intestinal endoderm.
AB  - Wnt signaling has been implicated in many developmental processes, but its role
      in early endoderm development is not well understood. Wnt signaling is active in
      posterior endoderm as early as E7.5. Genetic and chemical activation show that
      the Wnt pathway acts directly on endoderm to induce the intestinal master
      regulator Cdx2, shifting global gene away from anterior endoderm and toward a
      posterior, intestinal program. In a mouse embryonic stem cell differentiation
      platform that yields pure populations of definitive endoderm, Wnt signaling
      induces intestinal gene expression in all cells. We have identified a set of
      genes specific to the anterior small intestine, posterior small intestine, and
      large intestine during early development, and show that Wnt, through Cdx2,
      activates large intestinal gene expression at high doses and small intestinal
      gene expression at lower doses. These findings shed light on the mechanism of
      embryonic intestinal induction and provide a method to manipulate intestinal
      development from embryonic stem cells.

PMID- 21854847
TI  - A propositional representation model of anatomical and functional brain data.
AB  - Networks can represent a large number of systems. Recent advances in the domain
      of networks have been transferred to the field of neuroscience. For example, the
      graph model has been used in neuroscience research as a methodological tool to
      examine brain networks organization, topology and complex dynamics, as well as a
      framework to test the structure-function hypothesis using neuroimaging data. In
      the current work we propose a graph-theoretical framework to represent
      anatomical, functional and neuropsychological assessment instruments information.
      On the one hand, interrelationships between anatomic elements constitute an
      anatomical graph. On the other hand, a functional graph contains several
      cognitive functions and their more elementary cognitive processes. Finally, the
      neuropsychological assessment instruments graph includes several
      neuropsychological tests and scales linked with their different sub-tests and
      variables. The two last graphs are connected by relations of type "explore"
      linking a particular instrument with the cognitive function it explores. We
      applied this framework to a sample of patients with focal brain damage. Each
      patient was related to: (i) the cerebral entities injured (assessed with
      structural neuroimaging data) and (ii) the neusopsychological assessment tests
      carried out (weight by performance). Our model offers a suitable platform to
      visualize patients' relevant information, facilitating the representation,
      standardization and sharing of clinical data. At the same time, the integration
      of a large number of patients in this framework will make possible to explore
      relations between anatomy (injured entities) and function (performance in
      different tests assessing different cognitive functions) and the use of
      neurocomputational tools for graph analysis may help diagnostic and contribute to
      the comprehension of neural bases of cognitive functions.

PMID- 21854848
TI  - Cyanide preconditioning protects brain endothelial and NT2 neuron-like cells
      against glucotoxicity: role of mitochondrial reactive oxygen species and HIF
      1alpha.
AB  - The current study was undertaken to address the role of mitochondrial reactive
      oxygen species (ROS), and hypoxia inducible factor-1 alpha (HIF-1alpha) signaling
      pathway in the protection against high glucose levels in brain endothelial and
      NT2 neuron-like cells. Rat brain endothelial cells (RBE4) treated with non-toxic
      concentrations of cyanide (<=1 MUM; 1h) exhibited an increase in ROS levels,
      particularly hydrogen peroxide (H(2)O(2)). Cyanide also induced a modest
      mitochondrial depolarization, an increase in oxygen consumption and a structural
      (smaller mitochondria) and spatial (perinuclear region) reorganization of
      mitochondrial network. The stabilization and nuclear activation of HIF-1alpha in
      the presence of cyanide were also observed, which resulted in an increase in
      vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase
      (eNOS) and erythropoietin (EPO) protein levels reflecting an adaptive response.
      Importantly, preconditioning induced by cyanide protected brain endothelial cells
      against high glucose-mediated damage by the prevention of apoptotic cell death.
      In mitochondrial DNA-depleted NT2 (NT2 rho0) cells, cyanide (0.1 MUM) was unable
      to stimulate ROS production and, consequently, protect against glucotoxicity.
      Conversely, in NT2 cells, the parental cells with functional mitochondria,
      cyanide significantly increased ROS levels protecting against high glucose
      induced neuronal cell loss and activation of caspase-3. The free radical
      scavenger N-acetyl-L-cysteine and the specific HIF-1alpha inhibitor 2
      methoxyestradiol completely abolished the protective effects of cyanide
      preconditioning. Altogether our results demonstrate that mitochondrial
      preconditioning induced by cyanide triggers a protective response mediated by
      mitochondrial ROS and HIF-1alpha activation and signaling, which render brain
      endothelial and neuronal cells resistant against glucotoxicity.

PMID- 21854849
TI  - Fibroblast growth factor 1 (FGFR1) modulation regulates repair capacity of
      oligodendrocyte progenitor cells following chronic demyelination.
AB  - The adult mammalian brain contains multiple populations of endogenous progenitor
      cell types. However, following CNS trauma or disease, the regenerative capacity
      of progenitor populations is typically insufficient and may actually be limited
      by non-permissive or inhibitory signals in the damaged parenchyma. Remyelination
      is the most effective and simplest regenerative process in the adult CNS yet is
      still insufficient following repeated or chronic demyelination. Our previous in
      vitro studies demonstrated that fibroblast growth factor receptor 1 (FGFR1)
      signaling inhibited oligodendrocyte progenitor (OP) differentiation into mature
      oligodendrocytes. Therefore, we questioned whether FGFR1 signaling may inhibit
      the capacity of OP cells to generate oligodendrocytes in a demyelinating disease
      model and whether genetically reducing FGFR1 signaling in oligodendrocyte lineage
      cells could enhance the capacity for remyelination. FGFR1 was found to be
      upregulated in the corpus callosum during cuprizone mediated demyelination and
      expressed on OP cells just prior to remyelination. Plp/CreER(T):Fgfr1(fl/fl) mice
      were administered tamoxifen to induce conditional Fgfr1 deletion in
      oligodendrocyte lineage cells. Tamoxifen administration during chronic
      demyelination resulted in reduced FGFR1 expression in OP cells. OP proliferation
      and population size were not altered one week after tamoxifen treatment.
      Tamoxifen was then administered during chronic demyelination and mice were given
      a six week recovery period without cuprizone in the chow. After the recovery
      period, OP numbers were reduced and the number of mature oligodendrocytes was
      increased, indicating an effect of FGFR1 reduction on OP differentiation.
      Importantly, tamoxifen administration in Plp/CreER(T):Fgfr1(fl/fl) mice
      significantly promoted remyelination and axon integrity. These results
      demonstrate a direct effect of FGFR1 signaling in oligodendrocyte lineage cells
      as inhibiting the repair capacity of OP cells following chronic demyelination in
      the adult CNS.

PMID- 21854850
TI  - Pyruvate incubation enhances glycogen stores and sustains neuronal function
      during subsequent glucose deprivation.
AB  - The use of energy substrates, such as lactate and pyruvate, has been shown to
      improve synaptic function when administered during glucose deprivation. In the
      present study, we investigated whether prolonged incubation with monocarboxylate
      (pyruvate or lactate) prior rather than during glucose deprivation can also
      sustain synaptic and metabolic function. Pyruvate pre-incubation(3-4h)
      significantly prolonged (>25 min) the tolerance of rat hippocampal slices to
      delayed glucose deprivation compared to control and lactate pre-incubated slices,
      as revealed by field excitatory post synaptic potentials (fEPSPs); pre-incubation
      with pyruvate also reduced the marked decrease in NAD(P)H fluorescence resulting
      from glucose deprivation. Moreover, pyruvate exposure led to the enhancement of
      glycogen stores with time, compared to glucose alone (12 MUmol/g tissue at 4h vs.
      3.5 MUmol/g tissue). Prolonged resistance to glucose deprivation following
      exogenous pyruvate incubation was prevented by glycogenolysis inhibitors,
      suggesting that enhanced glycogen mediates the delay in synaptic activity
      failure. The application of an adenosine A1 receptor antagonist enhanced glycogen
      utilization and prolonged the time to synaptic failure, further confirming this
      hypothesis of the importance of glycogen. Moreover, tissue levels of ATP were
      also significantly maintained during glucose deprivation in pyruvate pretreated
      slices compared to control and lactate. In summary, these experiments indicate
      that pyruvate exposure prior to glucose deprivation significantly increased the
      energy buffering capacity of hippocampal slices, particularly by enhancing
      internal glycogen stores, delaying synaptic failure during glucose deprivation by
      maintaining ATP levels, and minimizing the decrease in the levels of NAD(P)H.

PMID- 21854851
TI  - Assays for monitoring viral manipulation of host ARE-mRNA turnover.
AB  - Early host responses to viral infection rapidly induce an antiviral gene
      expression program that limits viral replication and recruits sentinel cells of
      the innate immune system. These responses are mediated by cytokines. The mRNAs
      that encode cytokines typically harbor destabilizing adenine- and uridine-rich
      elements (AREs) that direct their constitutive degradation in the cytoplasm. In
      response to a variety of signals, including viral infection, small pools of
      cytoplasmic ARE-mRNAs are rapidly stabilized and translated. Thus, mRNA stability
      plays a key role in antiviral gene expression. Intriguingly, recent studies have
      identified viral proteins that specifically target ARE-mRNAs for stabilization,
      suggesting that certain proteins encoded by ARE-mRNAs may be advantageous for
      infection. Here, we discuss the development of a suite of sensitive and
      complementary assays to monitor ARE-mRNA turnover. These include luciferase- and
      destabilized-GFP-based assays that can be adapted for high-throughput screening
      applications.

PMID- 21854853
TI  - Identification and cloning of a transglutaminase from giant freshwater prawn,
      Macrobrachium rosenbergii, and its transcription during pathogen infection and
      moulting.
AB  - Complementary (c)DNA encoding transglutaminase (TG) messenger (m)RNA of the giant
      freshwater prawn, Macrobrachium rosenbergii, was cloned from haemocytes by a
      reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification
      of cDNA ends (RACE) using oligonucleotide primers based on the TG sequence of the
      horseshoe crab, Tachypleus tridentatus; tiger shrimp, Penaeus monodon; kuruma
      shrimp, Marsupenaeus japonicus; and crayfish, Pacifastacus leniusculus. The 2722
      bp cDNA contained an open reading frame (ORF) of 2334 bp, a 72-bp 5'-untranslated
      region (UTR), and a 316-bp 3'-UTR containing a stop codon and a poly A tail. The
      molecular mass of the deduced amino acid (aa) sequence (778 aa) was 86.67 kDa
      with an estimated pI of 5.4. The M. rosenbergii TG (abbreviated MrTG, accession
      no.: JF309296) contains a typical transglutaminase-like homologue, two putative
      integrin-binding motifs (RGD), ten glycosylation sites, and four calcium-binding
      sites; a catalytic triad is present as in arthropod TGs. Sequence comparison and
      a phylogenetic analysis revealed that shrimp TG can be separated into three
      subgroups, penaeid TG1, freshwater crustacean TG2 and marine crustacean TG2, and
      MrTG was more closely related to TG2 than to TG1. MrTG mRNA and TG activities
      were detected in all tested tissues of M. rosenbergii, with MrTG mainly being
      synthesised by haemocytes. There was a negative correlation between clotting time
      of haemolymph, and MrTG expression and TG activity of haemocytes in prawn
      injected with Lactococcus garvieae. The pattern of MrTG mRNA expression and TG
      activity in haemocytes exhibited a contrary tendency with clotting time of
      haemolymph during the moult stages. Those results indicate that cloned MrTG is
      involved in the defence response, and is probably the major functional TG for
      haemolymph coagulation in M. rosenbergii.

PMID- 21854852
TI  - Crystallization chaperone strategies for membrane proteins.
AB  - From G protein-coupled receptors to ion channels, membrane proteins represent
      over half of known drug targets. Yet, structure-based drug discovery is hampered
      by the dearth of available three-dimensional models for this large category of
      proteins. Other than efforts to improve membrane protein expression and
      stability, current strategies to improve the ability of membrane proteins to
      crystallize involve examining many orthologs and DNA constructs, testing the
      effects of different detergents for purification and crystallization, creating a
      lipidic environment during crystallization, and cocrystallizing with covalent or
      non-covalent soluble protein chaperones with an intrinsic high propensity to
      crystallize. In this review, we focus on this last category, highlighting
      successes of crystallization chaperones in membrane protein structure
      determination and recent developments in crystal chaperone engineering, including
      molecular display to enhance chaperone crystallizability, and end with a novel
      generic approach in development to target any membrane protein of interest.

PMID- 21854854
TI  - Molecular cloning, characterization and expression patterns of HSP60 in the grass
      carp (Ctenopharyngodon idella).
AB  - HSP60 is a highly immunogenic molecule, which is able to activate a large number
      of T cell types and is implicated in a variety of autoimmune diseases. The grass
      carp (Ctenopharyngodon idella), a freshwater fish species of the family
      Cyprinidae, accounts for the third biggest value (USD 4.8 billion) at single
      species level of major cultured fish species in the world. Here, we isolated and
      characterized the HSP60 cDNA from grass carp (designated as CiHSP60). Its cDNA
      was 2434 bp in length and encoded a putative protein of 575 amino acids. BLAST
      analysis revealed that the CiHSP60 gene shared a high similarity with other known
      HSP60 sequences. CiHSP60 contained all three classical HSP60 family signatures.
      The mRNA of CiHSP60 was constitutively expressed in all tested tissues of
      untreated grass carp, including brain, muscle, trunk kidney, liver, head kidney,
      skin, spleen, heart, gill, intestine, and fin, with the highest expression level
      in the blood. CiHSP60 transcript was present in unfertilized eggs, which suggests
      that CiHSP60 transcription is maternally inherited. Fluorescent real-time
      quantitative RT-PCR was used to examine the expression of the CiHSP60 gene in
      grass carp after the challenge with the bacterium Aeromonas hydrophila. A clear
      time-dependent expression pattern of CiHSP60 was found after the bacterial
      challenge, and the mRNA expression reached a maximum level at three days post
      challenge, and returned to control levels after seven days. The upregulated mRNA
      expression of CiHSP60 in grass carp after bacterial challenge indicates that the
      HSP60 gene is inducible and involved in immune responses. These results suggest
      that CiHSP60 plays an important role in A. hydrophila-related diseases and in
      early embryonic development stages in grass carp.

PMID- 21854856
TI  - Neuroergonomics: the brain in action and at work.

PMID- 21854855
TI  - Evaluative and generative modes of thought during the creative process.
AB  - Psychological theories have suggested that creativity involves a twofold process
      characterized by a generative component facilitating the production of novel
      ideas and an evaluative component enabling the assessment of their usefulness.
      The present study employed a novel fMRI paradigm designed to distinguish between
      these two components at the neural level. Participants designed book cover
      illustrations while alternating between the generation and evaluation of ideas.
      The use of an fMRI-compatible drawing tablet allowed for a more natural drawing
      and creative environment. Creative generation was associated with preferential
      recruitment of medial temporal lobe regions, while creative evaluation was
      associated with joint recruitment of executive and default network regions and
      activation of the rostrolateral prefrontal cortex, insula, and temporopolar
      cortex. Executive and default regions showed positive functional connectivity
      throughout task performance. These findings suggest that the medial temporal lobe
      may be central to the generation of novel ideas and creative evaluation may
      extend beyond deliberate analytical processes supported by executive brain
      regions to include more spontaneous affective and visceroceptive evaluative
      processes supported by default and limbic regions. Thus, creative thinking
      appears to recruit a unique configuration of neural processes not typically used
      together during traditional problem solving tasks.

PMID- 21854857
TI  - Cortical thickness is associated with gait disturbances in cerebral small vessel
      disease.
AB  - Although gait disturbances are present in a substantial portion of patients with
      cerebral small vessel disease (SVD), their pathogenesis has not been clarified as
      they are not entirely explained by the white matter lesions (WMLs) and lacunar
      infarcts. The role of cortical thickness in these patients remains largely
      unknown. We aimed to assess the regions of cortical thickness associated with
      distinct gait parameters in patients with SVD, and whether these associations
      were dependent on WMLs and lacunar infarcts. MRI data were obtained from 415
      subjects with SVD, aged between 50 and 85 years. We assessed cortical thickness
      using surface-based cortical thickness analysis, and gait performance using the
      GAITRite system. Cortical thickness of predominantly the orbitofrontal and
      ventrolateral prefrontal cortex, the inferior parietal lobe, cingulate areas and
      visual association cortices was positively related to stride length. Thickness of
      the primary and supplementary motor cortices and the cingulate cortex was
      positively related to cadence, while thickness of the orbitofrontal and
      ventrolateral prefrontal cortex, anterior cingulate cortex and especially the
      inferior parietal lobe and superior temporal gyrus was negatively related to
      stride width. The associations with stride length and width were partially
      explained by the subcortical WMLs and lacunar infarcts. Cortical thickness may
      therefore be important in gait disturbances in individuals with SVD, with
      different cortical patterns for specific gait parameters. We suggest that
      cortical atrophy is part of the disease processes in patients with SVD.

PMID- 21854859
TI  - Molecular phylogeny and diversification of the "Haenydra" lineage (Hydraenidae,
      genus Hydraena), a north-Mediterranean endemic-rich group of rheophilic
      Coleoptera.
AB  - Hydraena is the largest genus within the water beetle family Hydraenidae, with
      ca. 1000 species distributed worldwide. Within this large genus some monophyletic
      groups of species are recognised, among them the "Haenydra" lineage, including
      ca. 90 species distributed in the western Palaearctic from the Iberian peninsula
      to Iran. Species of "Haenydra" have often very restricted distributions, and are
      typical of clean small rivers and streams. We obtained ca. 2.5Kb of mitochondrial
      and nuclear protein-code and ribosomal markers of 101 specimens of 69 species of
      "Haenydra", and used Bayesian and Maximum Likelihood phylogenetic methods to
      reconstruct their phylogeny and diversification history. We found a derived
      phylogenetic position of the "Haenydra" lineage within the genus Hydraena, as
      sister to the species of the Hydraenabisulcata group. Within "Haenydra" three
      main lineages were recognised, with poorly resolved relationships among them: the
      Hydraena iberica, Hydraena gracilis and Hydraena dentipes lineages, the former
      restricted to the Iberian peninsula but the latter two distributed through the
      whole north-Mediterranean area. A Bayesian relaxed molecular clock approach using
      a combined mitochondrial rate of 2% divergence per MY estimated the origin of
      "Haenydra" in the Tortonian, ca. 8Mya, and the main diversification and the
      origin of most extant species in the Pliocene and Pleistocene. We did not found
      evidence of a phylogenetic connection between the western and eastern species
      that could be traced to the Messinian salinity crisis, with dispersal only at
      small geographical scales (e.g. the colonisation of Corsica and Sardinia from NW
      Italy and SW France). The H. gracilis and H. iberica lineages were estimated to
      have diversified under a pure birth model with a speciation rate of 0.64 and 0.23
      species/MY respectively, while the H. dentipes lineage was estimated to have a
      decreasing diversification rate with time, with an average rate of 0.29 sp/MY.

PMID- 21854858
TI  - Normal amygdala activation but deficient ventrolateral prefrontal activation in
      adults with bipolar disorder during euthymia.
AB  - Functional neuroimaging studies have implicated the involvement of the amygdala
      and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar
      disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been
      reported in manic bipolar patients scanned during the performance of an affective
      faces task. Whether this pattern of dysfunction persists during euthymia is
      unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar
      and 26 demographically matched healthy control subjects were scanned while
      performing an affective task paradigm involving the matching and labeling of
      emotional facial expressions. Neuroimaging results showed that, while amygdala
      activation did not differ significantly between groups, euthymic patients showed
      a significant decrease in activation of the right vlPFC (BA47) compared to
      healthy controls during emotion labeling. Additionally, significant decreases in
      activation of the right insula, putamen, thalamus and lingual gyrus were observed
      in euthymic bipolar relative to healthy control subjects during the emotion
      labeling condition. These data, taken in context with prior studies of bipolar
      mania using the same emotion recognition task, could suggest that amygdala
      dysfunction may be a state-related abnormality in bipolar disorder, whereas vlPFC
      dysfunction may represent a trait-related abnormality of the illness.
      Characterizing these patterns of activation is likely to help in understanding
      the neural changes related to the different mood states in bipolar disorder, as
      well as changes that represent more sustained abnormalities. Future studies that
      assess mood-state related changes in brain activation in longitudinal bipolar
      samples would be of interest.

PMID- 21854860
TI  - Airway responsiveness in an allergic rabbit model.
AB  - BACKGROUND: Animal models of allergy and bronchial hyperresponsiveness (BHR) are
      useful in researching pulmonary diseases and evaluating drug effects on the
      airways. Neonatally immunised rabbits exhibit several features of asthma as
      adults, including early and late airway responses following antigen challenge,
      oedema and inflammatory cell infiltration into the lung, BHR to inhaled histamine
      and methacholine (compared with naive rabbits) and exacerbations of BHR following
      antigen challenge. Therefore this model can be used to investigate the underlying
      mechanisms of BHR and for the preclinical evaluation of new drugs for the
      treatment of asthma. AIM: To describe the characteristics of airway responses in
      a rabbit model of allergic inflammation and to evaluate the relationship between
      skin test reactivity to antigen, airway inflammation and BHR. METHODS: New
      Zealand White rabbits were neonatally immunised against Alternaria tenius. At 3
      months of age, airway responsiveness was measured to aerosolised histamine,
      methacholine or allergen. Bronchoalveolar lavage (BAL) was performed and cell
      counts recorded. Direct skin tests were performed to assess skin reactivity to
      allergen and passive cutaneous anaphylaxis (PCA) tests were performed to
      determine titres of circulating IgE. RESULTS: In a population of allergic
      rabbits, allergen challenge induced a significant bronchoconstriction, airway
      inflammation and BHR. Skin test responsiveness to allergen did not correlate with
      various indices of pulmonary mechanics e.g. baseline sensitivity to methacholine
      and histamine, or allergen-induced BHR. In contrast, skin test responsiveness did
      predict airway inflammation as assessed by measurements of eosinophil recruitment
      to the lung. CONCLUSION: The allergic rabbit is a useful model to further our
      understanding of allergic diseases. Recording lung function using a minimally
      invasive procedure allows repeated measurements to be made in rabbits
      longitudinally, and each animal may thus be used as its own control. Our
      observations do not support the use of skin responsiveness to allergen as a
      predictor of airway sensitivity as we observed no correlation between skin
      sensitivity and airway responsiveness to inhaled histamine, methacholine or
      allergen. However, skin reactivity did predict airway inflammation as assessed by
      measurements of eosinophil recruitment to the lung. Our results also further
      highlight the likely dissociation between airway inflammation and BHR.

PMID- 21854861
TI  - The Mediator complex: crucial functions in transcription with links to
      development and disease.

PMID- 21854862
TI  - Mediator complex proteins are required for diverse developmental processes.
AB  - The Mediator complex serves a crucial function in gene regulation, forming a link
      between gene-specific transcription factors and RNA polymerase II. Most protein
      coding genes therefore require Mediator complex activity for transcriptional
      regulation. Given the essential functions performed by Mediator complex proteins
      in gene regulation, it is not surprising that mutations in Mediator complex genes
      disrupt animal and plant development. What is more intriguing is that the
      phenotypes of individual Mediator complex mutants are distinct from each other,
      demonstrating that certain developmental processes have a greater requirement for
      specific Mediator complex genes. Additionally, the range of developmental
      processes that are altered in Mediator complex mutants is broad, affecting a
      variety of cell types and physiological systems. Gene expression defects in
      Mediator complex mutants reveal distinct roles for individual Mediator proteins
      in transcriptional regulation, suggesting that the deletion of one Mediator
      complex protein does not interfere with transcription in general, but instead
      alters the expression of specific target genes. Mediator complex proteins may
      have diverse roles in different organisms as well, as mutants in the same
      Mediator gene in different species can display dissimilar phenotypes.

PMID- 21854864
TI  - Seminars in Cell & Developmental Biology. Anaphase promoting complex, control of
      mitosis, and beyond & micronutrient and mineral supply in developmental biology.
      Editorial.

PMID- 21854865
TI  - Cyclic CO(2) emissions during the high temperature pulse of fluctuating thermal
      regime in eye-pigmented pupae of Megachile rotundata.
AB  - Megachile rotundata (Hymenoptera: Megachilidae), the primary pollinator used in
      alfalfa seed production, may need to be exposed to low-temperature storage to
      slow the insects' development to better match spring emergence with the alfalfa
      bloom. It has been demonstrated that using a fluctuating thermal regime (FTR)
      improves the tolerance of pupae to low temperatures. Carbon dioxide emission
      rates were compared between four different FTRs, all with a base temperature of 6
      degrees C and a daily high-temperature pulse. Four different high-temperature
      pulses were examined, 15 or 25 degrees C for 2h and 20 degrees C for 1 or 2h. A
      subset of pupae at the FTR base temperature of 6 degrees C exhibited continuous
      gas exchange and, once ramped to 20 or 25 degrees C, shifted to cyclic gas
      exchange. As temperatures were ramped down from the high-temperature pulse to 6
      degrees C, the pupae reverted to continuous gas exchange. The following
      conclusions about the effect of FTR on the CO(2) emissions of M. rotundata pupae
      exposed to low-temperature storage during the spring incubation were reached: 1)
      the high temperature component of the FTR was the best predictor of respiratory
      pattern; 2) neither pupal body mass nor days in FTR significantly affected which
      respiratory pattern was expressed during FTRs; 3) cyclic gas exchange was induced
      only in pupae exposed to temperatures greater than 15 degrees C during the FTR
      high temperature pulse; and 4) a two hour pulse at 25 degrees C doubled the
      number of CO(2) peaks observed during the FTR pulse as compared to a two hour
      pulse at 20 degrees C.

PMID- 21854863
TI  - Mediator-dependent nuclear receptor function.
AB  - As gene-specific transcription factors, nuclear receptors are broadly involved in
      many important biological processes. Their function on target genes requires the
      stepwise assembly of different coactivator complexes that facilitate chromatin
      remodeling and subsequent preinitiation complex (PIC) formation and function.
      Mediator has proved to be a crucial, and general, nuclear receptor-interacting
      coactivator, with demonstrated functions in transcription steps ranging from
      chromatin remodeling to subsequent PIC formation and function. Here we discuss
      our current understanding of (i) pathways involved in Mediator recruitment and
      function through nuclear receptor target gene enhancers and promoters, (ii)
      conditional requirements for the strong nuclear receptor-Mediator interactions
      mediated by NR AF2 domains and the MED1 LXXLL motifs, (iii) Mediator functions,
      through different nuclear receptor-interacting subunits, in different metabolic
      pathways, (iv) emerging functions of Mediator as a corepressor in addition to its
      major role as a coactivator and (v) mechanisms by which Mediator acts to transmit
      signals from enhancer-bound nuclear receptors to the general transcription
      machinery at core promoters to effect PIC formation and function. As a nuclear
      receptor coregulator with increasingly diverse functions, Mediator may thus
      modulate nuclear receptor signaling through several different mechanisms.

PMID- 21854866
TI  - Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception.
AB  - The soluble epoxide hydrolase (sEH) enzyme regulates the levels of endogenous
      epoxygenated fatty acid (EFA) lipid metabolites by rapidly degrading these
      molecules. The EFAs have pleiotropic biological activities including the
      modulation of nociceptive signaling. Recent findings indicate that the EFAs, in
      particular the arachidonic acid (AA) derived epoxyeicosatrienoic acids (EETs),
      the docosahexaenoic acid (DHA) derived epoxydocosapentaenoic acids (EpDPEs) and
      eicosapentaenoic acid (EPA) derived epoxyeicosatetraenoic acids (EpETEs) are
      natural signaling molecules. The tight regulation of these metabolites speaks to
      their importance in regulating biological functions. In the past several years
      work on EFAs in regard to their activities in the nervous system evolved to
      demonstrate that these molecules are anti-inflammatory and anti-nociceptive. Here
      we focus on the recent advances in understanding the effects of sEH inhibition
      and increased EFAs on the nociceptive system and their ability to reduce pain.
      Evidence of their role in modulating pain signaling is given by their direct
      application and by inhibiting their degradation in various models of pain.
      Moreover, there is mounting evidence of EFAs role in the crosstalk between major
      nociceptive and anti-nociceptive systems which is reviewed herein. Overall the
      fundamental knowledge generated within the past decade indicates that orally
      bioavailable small molecule inhibitors of sEH may find a place in the treatment
      of a number of diverse painful conditions including inflammatory and neuropathic
      pain.

PMID- 21854868
TI  - Fas/FasL-dependent and -independent activation of caspase-8 in doxorubicin
      treated human breast cancer MCF-7 cells: ADAM10 down-regulation activates
      Fas/FasL signaling pathway.
AB  - The contribution of Fas-mediated death pathway to doxorubicin-induced death of
      MCF-7 cells is not unambiguously elucidated. Thus, this study was conducted to
      explore doxorubicin-induced Fas/FasL signaling pathway activation in MCF-7 cells
      and doxorubicin-resistant MCF-7 (MCF-7/Dox) cells. Doxorubicin-induced caspase-8
      activation was found to be mediated through Akt/ERK inactivation and FasL
      independent Fas pathway in MCF-7 cells, while caspase-8 activation in MCF-7/Dox
      cells depended exclusively on FasL-stimulated Fas pathway. Suppression of caspase
      8 activation restored the viability of doxorubicin-treated MCF-7 cells and MCF
      7/Dox cells. Contrary to FasL surface expression exclusively detected in MCF
      7/Dox cells, intracellular FasL expression was noted with MCF-7 cells. Promotion
      of FasL translocation to the cell surface by lysophosphatidic acid evoked a FasL
      activated Fas death pathway in MCF-7 cells. Doxorubixin-evoked beta-TrCP up
      regulation promoted Sp1 degradation, which subsequently suppressed ADAM10
      expression in MCF-7 and MCF-7/Dox cells. Doxorubicin-induced down-regulation of
      ADAM10 reduced FasL shedding, leading to Fas pathway activation in MCF-7/Dox
      cells. Knock-down of ADAM10 induced death in MCF-7/Dox cells, but marginally
      reduced the viability of MCF-7 cells. Taken together, our data indicate that
      Akt/ERK-mediated caspase-8 activation and Fas/FasL-mediated caspase-8 activation
      mostly elucidate doxorubicin-induced death in MCF-7 cells and MCF-7/Dox cells,
      respectively. These observations suggest a promising therapeutic modality for
      overcoming doxorubicin-resistant breast cancer by targeting ADAM10 sheddase
      activity.

PMID- 21854867
TI  - Notch signaling and Notch signaling modifiers.
AB  - Originally discovered nearly a century ago, the Notch signaling pathway is
      critical for virtually all developmental programs and modulates an astounding
      variety of pathogenic processes. The DSL (Delta, Serrate, LAG-2 family) proteins
      have long been considered canonical activators of the core Notch pathway. More
      recently, a wide and expanding network of non-canonical extracellular factors has
      also been shown to modulate Notch signaling, conferring newly appreciated
      complexity to this evolutionarily conserved signal transduction system. Here, I
      review current concepts in Notch signaling, with a focus on work from the last
      decade elucidating novel extracellular proteins that up- or down-regulate signal
      potency.

PMID- 21854869
TI  - The emerging role of nuclear factor kappa B in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC), the commonest type of kidney cancer, is a highly
      metastatic and the deadliest of all urologic cancers. Despite the development of
      many novel chemotherapeutics in recent years, metastatic RCC remains an incurable
      and lethal disease. The imperative for the identification of novel molecular
      targets and more effective therapeutics for metastatic RCC remain. One promising
      target is the transcription factor nuclear factor kappa B (NF-kappaB). NF-kappaB
      is unique in the sense that it regulates all important aspects of RCC biology
      that pose challenge to conventional therapy - resistance to apoptosis,
      angiogenesis and multi-drug resistance. Aberrations in the von Hippel Lindau gene
      (VHL) are the most important risk factor for the development of RCC, especially
      the clear cell type, which constitutes 70-80% of RCC. VHL is a negative regulator
      of NF-kappaB. In the absence of a functional VHL, the expression and activity of
      NF-kappaB are enhanced, which subsequently confer drug resistance and promote
      epithelial-mesenchymal-transition of RCC. This review provides an overview of
      RCC, its molecular mechanisms, the role of NF-kappaB in carcinomas including RCC,
      and the rationale for NF-kappaB as a target molecule.

PMID- 21854870
TI  - Comparative histopathology of Opisthorchis felineus and Opisthorchis viverrini in
      a hamster model: an implication of high pathogenicity of the European liver
      fluke.
AB  - European liver fluke (Opisthorchis felineus) and Asian liver fluke (Opisthorchis
      viverrini) are similar in morphology but comparative pathology of the infections
      has not been described. We therefore did comparative histopathology of both
      parasites in an experimental animal model. The study was conducted in 3 groups of
      105 Syrian golden hamsters; the first and second groups fed with 50 metacercariae
      of O. felineus (OF) or O. viverrini (OV) and the last group was uninfected
      controls. Five hamsters in each group were euthanized on weeks 1, 2, 4, 8, 12 and
      24 post-infection. The liver tissue was fixed and processed for routine
      histopathology and immunohistochemistry for proliferation markers (BrdU or PCNA).
      Overall, the liver histopathology of O. felineus and O. viverrini infection was
      generally similar. However, various histopathogical features including intense
      inflammation, fibrosis, biliary and goblet cell hyperplasia and dysplasia
      occurred earlier in the OF group. In addition, the existence of precancerous
      lesions such as cholangiofibrosis in a long-term infection was observed only in
      this group. O. felineus is larger in size than O. viverrini which, together with
      its excreted and secreted antigens, likely is crucial in the induction of liver
      fluke induced disease. The differences in nature and timing of the
      histopathological profile indicate that opisthorchiasis caused by the European
      liver fluke O. felineus is more pathogenic than its Asian relative O. viverrini.

PMID- 21854872
TI  - The effects of UV radiation on the visual system of the crab Neohelice granulata:
      a protective role of melatonin.
AB  - The first and main target-structure of ultraviolet (UV) radiation in animals is
      the body surface, including the skin and eyes. Here, we investigated cell damage
      in the visual system of the crab Neohelice granulata acclimated to constant light
      and exposed to UVA or UVB at 12:00 h for 30 min. The reactive oxygen species
      (ROS) production, antioxidant capacity against peroxyl radicals (ACAP), lipid
      peroxidation (LPO) damage, catalase (CAT) activity, and the melatonin
      immunohistochemical reactivity in the eyestalks were evaluated. The animals that
      received melatonin and were exposed to UVA and UVB radiation showed a decreased
      ROS concentration (p<0.05).The ACAP test showed a decrease (p<0.05) in their
      values when the animals received 2 pmol/crab of melatonin (physiological dose)
      before the exposure to UVA radiation. The animals exposed to UVB radiation after
      receiving the same dose of melatonin showed an increase (p<0.05) in the ACAP test
      compared with the animals exposed to UVB radiation after receiving only crab
      physiological saline. The CAT activity increased (p<0.05) in the animals that
      received melatonin and were exposed to UVA and UVB radiation. Animals exposed to
      UVA and UVB displayed an increase (p<0.05) in the LPO levels, whereas animals
      treated with melatonin showed lower (p<0.05) LPO levels when irradiated. The
      results indicate that the specific oxidative parameters altered by UV radiation
      can be modulated by a physiological dose of melatonin. Moreover, the melatonin
      regularly produced by virtually all eyestalk cells suggests that it may function
      to modulate the noxious effects of radiation, at least in the crab N. granulata.

PMID- 21854873
TI  - Design and development of a mobile computer application to reengineer workflows
      in the hospital and the methodology to evaluate its effectiveness.
AB  - This paper describes a new method of collecting additional data for the purpose
      of skin cancer research from the patients in the hospital using the system Mobile
      Computing in Medicine Graz (MoCoMed-Graz). This system departs from the
      traditional paper-based questionnaire data collection methods and implements a
      new composition of evaluation methods to demonstrate its effectiveness. The
      patients fill out a questionnaire on a Tablet-PC (or iPad Device) and the
      resulting medical data is integrated into the electronic patient record for
      display when the patient enters the doctor's examination room. Since the data is
      now part of the electronic patient record, the doctor can discuss the data
      together with the patient making corrections or completions where necessary, thus
      enhancing data quality and patient empowerment. A further advantage is that all
      questionnaires are in the system at the end of the day - and manual entry is no
      longer necessary - consequently raising data completeness. The front end was
      developed using a User Centered Design Process for touch tablet computers and
      transfers the data in XML to the SAP based enterprise hospital information
      system. The system was evaluated at the Graz University Hospital - where about 30
      outpatients consult the pigmented lesion clinic each day - following
      Bronfenbrenner's three level perspective: The microlevel, the mesolevel and the
      macrolevel: On the microlevel, the questions answered by 194 outpatients,
      evaluated with the System Usability Scale (SUS) resulted in a median of 97.5
      (min: 50, max: 100) which showed that it is easy to use. On the mesolevel, the
      time spent by medical doctors was measured before and after the implementation of
      the system; the medical task performance time of 20 doctors (age median 43 (min:
      29; max: 50)) showed a reduction of 90%. On the macrolevel, a cost model was
      developed to show how much money can be saved by the hospital management. This
      showed that, for an average of 30 patients per day, on a 250 day basis per year
      in this single clinic, the hospital management can save up to 40,000 EUR per
      annum, proving that mobile computers can successfully contribute to workflow
      optimization.

PMID- 21854871
TI  - Laboratory diagnosis of Clostridium difficile infection can molecular
      amplification methods move us out of uncertainty?
AB  - The laboratory diagnosis of Clostridium difficile infection (CDI) continues to be
      challenging. Recent guidelines from professional societies in the United States
      note that enzyme immunoassays for toxins A and B do not have adequate sensitivity
      to be used alone for detecting CDI, yet the optimal method for diagnosing this
      infection remains unclear. Nucleic acid amplification tests (NAATs) that target
      chromosomal toxin genes (usually the toxin B gene, tcdB) show high sensitivity
      and specificity, provide rapid results, and are amenable to both batch and on
      demand testing, but these tests were not universally recommended for routine use
      in the recent guidelines. Rather, two-step algorithms that use glutamate
      dehydrogenase (GDH) assays to screen for C. difficile in stool specimens,
      followed by either direct cytotoxin testing or culture to identify toxin
      producing C. difficile isolates, were recommended in one guideline and either GDH
      algorithms or NAATs were recommended in another guideline. Unfortunately, neither
      culture nor direct cytotoxin testing is widely available. In addition, this two
      step approach requires 48 to 92 hours to complete, which may delay the initiation
      of therapy and critical infection control measures. Recent studies also show the
      sensitivity of several GDH assays to be <90%. This review considers the role of
      NAATs for diagnosing CDI and explores their potential advantages over two-step
      algorithms, including shorter time to results, while providing comparable, if not
      superior, accuracy.

PMID- 21854874
TI  - MicroRNAs regulating cell pluripotency and vascular differentiation.
AB  - Human embryonic stem cells (hESC) offer broad potential for regenerative medicine
      owing to their capacity for self renewal, exponential scale up and
      differentiation into any cell type in the adult body. hESC have been proposed as
      a potentially unlimited source for the generation of transplantable, healthy,
      functional vascular cells for repair of ischemic tissues. To optimally harness
      this potential necessitates precise control over biological processes that govern
      maintenance, pluripotency and cell differentiation including signalling cascades,
      gene expression profiles and epigenetic modification. Such control may be
      elicited by microRNAs, which are powerful negative regulators of gene expression.
      Here, we review the role for miRNAs in both the maintenance of pluripotency and
      differentiation of cells to a cardiovascular lineage including endothelial cells,
      vascular smooth muscle cells and cardiomyocytes and put this into context for
      regenerative medicine in the cardiovascular system.

PMID- 21854875
TI  - Recombination and positive selection contributed to the evolution of Listeria
      monocytogenes lineages III and IV, two distinct and well supported uncommon L.
      monocytogenes lineages.
AB  - Listeriamonocytogenes lineages III and IV represent two uncommon lineages of the
      human and animal pathogen L. monocytogenes, characterized by occurrence of
      unusual phenotypic and genetic characteristics that differentiate them from the
      common lineages I and II. To gain further insights into the evolution of lineages
      III and IV, we amplified and sequenced housekeeping genes (i.e., gap, prs, purM,
      ribC, and sigB), internalin genes (i.e., inlA, inlB, inlC, inlG, inlC2, inlD,
      inlE, inlF, and inlH) and the virulence gene cluster containing prfA, plcA, hly,
      mpl, actA, and plcB for lineages III (n = 7) and IV (n = 4) isolates.
      Phylogenetic analyses of the sequences obtained along with previously reported
      sequence data for 40 isolates representing lineages I (n = 18), II (n = 21), and
      III (n = 1), showed that lineages III and IV represent divergent and monophyletic
      lineages. The virulence gene cluster as well as the inlAB operon were present in
      all isolates, with inlF absent from all lineages III and IV isolates. While all
      lineage IV isolates contained only inlC (in addition to inlAB), lineage III
      isolates showed considerable diversity with regard to internalin gene presence,
      including presence of (i) only inlC (n = 2), (ii) inlC and inlGC2DE (n = 3),
      (iii) only inlGC2DE (n = 2), and (iv) inlC and inlC2DE (n = 1). In addition to
      evidence for horizontal gene transfer events, among lineages III and IV isolates,
      in prs, actA, plcB, mpl, inlA, inlB, inlG, inlD, and inlE, we also found
      significant evidence for positive selection in the hly promoter region and, along
      the lineages III and IV branches, for actA (including in sites recognized for
      interactions with proteins involved in actin tail polymerization). In conclusion,
      lineages III and IV represent two distinct monophyletic groups with contributions
      of intragenic recombination to the evolution of their internalin genes as well as
      contributions of positive selection to evolution of the virulence genes island.

PMID- 21854876
TI  - Anti-tumor and immunomodulatory activity of resveratrol in vitro and its
      potential for combining with cancer immunotherapy.
AB  - We evaluated the anti-tumor effect of Resveratrol (RV) on M21 and NXS2 tumor cell
      lines and its immunosuppressive activity on human and murine immune cells to
      determine the potential for combining RV and immunotherapy. In vitro,
      concentrations of RV>=25 mcM, inhibited cell proliferation, blocked DNA synthesis
      and induced G1 phase arrest in tumor and immune cells. RV at 12-50 mcM inhibited
      antibody dependent cell mediated cytotoxicity (ADCC) of tumor cells facilitated
      by the hu14.18-IL2 immunocytokine (IC). The in vivo anti-tumor and
      immunomodulating activity of RV given systemically were assessed in mice. Results
      showed that this RV regimen inhibited the growth of NXS2 tumors in vivo but did
      not appear to interfere with blood cell count, splenocyte or macrophage function.
      Thus, RV may be a candidate for combining with immunotherapy.

PMID- 21854878
TI  - A novel approach for the characterisation of proteoglycans and biosynthetic
      enzymes in a snail model.
AB  - Proteoglycans encompass a heterogeneous group of glycoconjugates where proteins
      are substituted with linear, highly negatively charged glycosaminoglycan chains.
      Sulphated glycosaminoglycans are ubiquitous to the animal kingdom of the Eukarya
      domain. Information on the distribution and characterisation of proteoglycans in
      invertebrate tissues is limited and restricted to a few species. By the use of
      multidimensional protein identification technology and immunohistochemistry, this
      study shows for the first time the presence and tissue localisation of different
      proteoglycans, such as perlecan, aggrecan, and heparan sulphate proteoglycan,
      amongst others, in organs of the gastropoda Achatina fulica. Through a proteomic
      analysis of Golgi proteins and immunohistochemistry of tissue sections, we
      detected the machinery involved in glycosaminoglycan biosynthesis, related to
      polymer formation (polymerases), as well as secondary modifications (sulphation
      and uronic acid epimerization). Therefore, this work not only identifies both the
      proteoglycan core proteins and glycosaminoglycan biosynthetic enzymes in
      invertebrates but also provides a novel method for the study of glycosaminoglycan
      and proteoglycan evolution.

PMID- 21854879
TI  - Super-resolution segmentation of imaging mass spectrometry data: Solving the
      issue of low lateral resolution.
AB  - In the last decade, imaging mass spectrometry has seen incredible technological
      advances in its applications to biological samples. One computational method of
      data mining in this field is the spatial segmentation of a sample, which produces
      a segmentation map highlighting chemically similar regions. An important issue
      for any imaging mass spectrometry technology is its relatively low spatial or
      lateral resolution (i.e. a large size of pixel) as compared with microscopy.
      Thus, the spatial resolution of a segmentation map is also relatively low, that
      complicates its visual examination and interpretation when compared with
      microscopy data, as well as reduces the accuracy of any automated comparison. We
      address this issue by proposing an approach to improve the spatial resolution of
      a segmentation map. Given a segmentation map, our method magnifies it up to some
      factor, producing a super-resolution segmentation map. The super-resolution map
      can be overlaid and compared with a high-res microscopy image. The proposed
      method is based on recent advances in image processing and smoothes the
      "pixilated" region boundaries while preserving fine details. Moreover, it neither
      eliminates nor splits any region. We evaluated the proposed super-resolution
      segmentation approach on three MALDI-imaging datasets of human tissue sections
      and demonstrated the superiority of the super-segmentation maps over standard
      segmentation maps.

PMID- 21854881
TI  - Heat shock protein 60 protects skeletal tissue against glucocorticoid-induced
      bone mass loss by regulating osteoblast survival.
AB  - Excessive glucocorticoid administration accelerates osteoblast apoptosis and
      skeletal deterioration. Heat shock proteins (HSPs) regulate metabolic activities
      in osteoblastic cells. This study characterized the biological significance of
      HSP60 in glucocorticoid-induced bone loss. Rats were treated with glucocorticoid,
      HSP60 antisense oligonucleotides, or adenovirus-mediated HSP60 gene transfer.
      Bone mineral density, metaphyseal trabecular micro-architecture, and fragility
      were analyzed by dual X-ray absorptiometry, micro-computed tomography, and
      material testing, respectively. Differential proteomic profiles of bone tissue
      extracts were detected by bi-dimensional electrophoresis and mass spectrometry.
      Survival and proapoptotic signal transduction were quantified by immunoblotting.
      Glucocorticoid-treated rats had low bone mineral density and metaphyseal
      trabecular microstructure in association with downregulation of collagen 1alpha1
      and HSP60 expressions in bone tissue. Gain of HSP60 function by adenovirus
      mediated HSP60 gene transfer abrogated the deleterious effects of glucocorticoid
      treatment on bone mass, trabecular microstructure, and mechanical strength.
      Enhancement of HSP60 signaling attenuated the glucocorticoid-induced loss of
      trabecular bone volume, mineral acquisition reactions and osteoblast surface.
      HSP60 gene transfer activated ERK and Akt and reduced Bax and cytochrome c
      release, as well as caspase-3 cleavage, which attenuated the inhibitory effects
      of glucocorticoid treatment on osteoblast survival. Loss of HSP60 function by
      HSP60 antisense oligonucleotides accelerated mitochondrial apoptotic programs and
      osteoblast apoptosis. Knockdown of HSP60 induced loss of bone mass, micro
      architecture integrity, and mechanical property. Taken together, loss of HSP60
      signaling contributes to the glucocorticoid-induced enhancement of pro-apoptotic
      reactions, thereby accelerating osteoblast apoptosis and bone mass loss.
      Enhancement of HSP60 function is beneficial for protecting bone tissue against
      the glucocorticoid-induced inhibition of bone cell viability and bone formation.

PMID- 21854880
TI  - Trabecular bone loss after administration of the second-generation antipsychotic
      risperidone is independent of weight gain.
AB  - Second generation antipsychotics (SGAs) have been linked to metabolic and bone
      disorders in clinical studies, but the mechanisms of these side effects remain
      unclear. Additionally, no studies have examined whether SGAs cause bone loss in
      mice. Using in vivo and in vitro modeling we examined the effects of risperidone,
      the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were
      treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg
      daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced
      trabecular BV/TV, trabecular number and percent cortical area. Trabecular
      histomorphometry demonstrated increased resorption parameters, with no change in
      osteoblast number or function. Risperidone also altered adipose tissue
      distribution such that white adipose tissue mass was reduced and liver had
      significantly higher lipid infiltration. Next, in order to tightly control
      risperidone exposure, we administered risperidone by chronic subcutaneous
      infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old
      female B6 mice. Similar trabecular and cortical bone differences were observed
      compared to the orally treated groups (reduced trabecular BV/TV, and connectivity
      density, and reduced percent cortical area) with no change in body mass, percent
      body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated
      mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and
      BFR/BV). Resorption parameters were elevated, but this increase did not reach
      statistical significance. To determine if risperidone could directly affect bone
      cells, primary bone marrow cells were cultured with osteoclast or osteoblast
      differentiation media. Risperidone was added to culture medium in clinically
      relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly
      increased by addition in vitro of risperidone while osteoblast differentiation
      was not altered. These studies indicate that risperidone treatment can have
      negative skeletal consequences by direct activation of osteoclast activity and by
      indirect non-cell autonomous mechanisms. Our findings further support the tenet
      that the negative side effects of SGAs on bone mass should be considered when
      weighing potential risks and benefits, especially in children and adolescents who
      have not yet reached peak bone mass.

PMID- 21854877
TI  - Live-cell imaging of tumor proteolysis: impact of cellular and non-cellular
      microenvironment.
AB  - Our laboratory has had a longstanding interest in how the interactions between
      tumors and their microenvironment affect malignant progression. Recently, we have
      focused on defining the proteolytic pathways that function in the transition of
      breast cancer from the pre-invasive lesions of ductal carcinoma in situ (DCIS) to
      invasive ductal carcinomas (IDCs). We use live-cell imaging to visualize,
      localize and quantify proteolysis as it occurs in real-time and thereby have
      established roles for lysosomal cysteine proteases both pericellularly and
      intracellularly in tumor proteolysis. To facilitate these studies, we have
      developed and optimized 3D organotypic co-culture models that recapitulate the in
      vivo interactions of mammary epithelial cells or tumor cells with stromal and
      inflammatory cells. Here we will discuss the background that led to our present
      studies as well as the techniques and models that we employ. This article is part
      of a Special Issue entitled: Proteolysis 50 years after the discovery of
      lysosome.

PMID- 21854885
TI  - Parvovirus B19-induced type II mixed cryoglobulinemia.

PMID- 21854886
TI  - Improving influenza vaccination rates by targeting individuals not seeking early
      seasonal vaccination.

PMID- 21854887
TI  - Internal medicine residency redesign: proposal of the Internal Medicine Working
      Group.
AB  - Concerned with the quality of internal medicine training, many leaders in the
      field assembled to assess the state of the residency, evaluate the decline in
      interest in the specialty, and create a framework for invigorating the
      discipline. Although many external factors are responsible, we also found
      ourselves culpable: allowing senior role models to opt out of important training
      activities, ignoring a progressive atrophy of bedside skills, and focusing on
      lock-step curricula, lectures, and compiled diagnostic and therapeutic
      strategies. The group affirmed its commitment to a vision of internal medicine
      rooted in science and learned with mentors at the bedside. Key factors for new
      emphasis include patient-centered small group teaching, greater incorporation of
      clinical epidemiology and health services research, and better schedule control
      for trainees. Because previous proposals were weakened by lack of evidence, we
      propose to organize the Cooperative Educational Studies Group, a pool of training
      programs that will collect a common data set describing their programs, design
      interventions to be tested rigorously in multi-methodological approaches, and at
      the same time produce knowledge about high-quality practice.

PMID- 21854888
TI  - Cardiac resynchronization therapy: what? Who? When? How?
AB  - Cardiac resynchronization therapy is an important and underused tool to help
      patients with heart failure symptoms, left ventricular systolic dysfunction
      (LVEF<=35%), and intraventricular conduction system disease (QRS>=120 msec).
      Cardiac resynchronization therapy paces the heart simultaneously from both right
      and left ventricles (through the coronary sinus). Approximately three quarters of
      patients who undergo a successful implant will have some degree of symptomatic
      improvement and have fewer heart failure hospitalizations. When cardiac
      resynchronization therapy is combined with a defibrillator, patients may benefit
      from the added protection against sudden arrhythmic death.

PMID- 21854889
TI  - Black hairy tongue.

PMID- 21854890
TI  - Under pressure: where's the cirrhosis?

PMID- 21854891
TI  - Chief complaint: "people were staring".

PMID- 21854892
TI  - Weight and mortality following heart failure hospitalization among diabetic
      patients.
AB  - BACKGROUND: Type 2 diabetes is an important risk factor for heart failure and is
      common among patients with heart failure. The impact of weight on prognosis after
      hospitalization for acute heart failure among patients with diabetes is unknown.
      The objective of this study was to examine all-cause mortality in relation to
      weight status among patients with type 2 diabetes hospitalized for decompensated
      heart failure. METHODS: The Worcester Heart Failure Study included adults
      admitted with acute heart failure to all metropolitan Worcester medical centers
      in 1995 and 2000. The weight status of 1644 patients with diabetes (history of
      type 2 diabetes in medical record or admission serum glucose >=200 mg/dL) was
      categorized using body mass index calculated from height and weight at admission.
      Survival status was ascertained at 1 and 5 years after hospital admission.
      RESULTS: Sixty-five percent of patients were overweight or obese and 3% were
      underweight. Underweight patients had 50% higher odds of all-cause mortality
      within 5 years of hospitalization for acute heart failure than normal weight
      patients. Class I and II obesity were associated with 20% and 40% lower odds of
      dying. Overweight and Class III obesity were not associated with mortality.
      Results were similar for mortality within 1 year of hospitalization for acute
      heart failure. CONCLUSIONS: The mechanisms underlying the association between
      weight status and mortality are not fully understood. Additional research is
      needed to explore the effects of body composition, recent weight changes, and
      prognosis after hospitalization for heart failure among patients with diabetes.

PMID- 21854893
TI  - Meta-analysis comparing Mediterranean to low-fat diets for modification of
      cardiovascular risk factors.
AB  - BACKGROUND: Evidence from individual trials comparing Mediterranean to low-fat
      diets to modify cardiovascular risk factors remains preliminary. METHODS: We
      systematically searched MEDLINE, EMBASE, Biosis, Web of Science, and the Cochrane
      Central Register of Controlled Trials from their inception until January 2011, as
      well as contacted experts in the field, to identify randomized controlled trials
      comparing Mediterranean to low-fat diets in overweight/obese individuals, with a
      minimum follow-up of 6 months, reporting intention-to-treat data on
      cardiovascular risk factors. Two authors independently assessed trial eligibility
      and quality. RESULTS: We identified 6 trials, including 2650 individuals (50%
      women) fulfilling our inclusion criteria. Mean age of enrolled patients ranged
      from 35 to 68 years, mean body mass index from 29 to 35 kg/m(2). After 2 years of
      follow-up, individuals assigned to a Mediterranean diet had more favorable
      changes in weighted mean differences of body weight (-2.2 kg; 95% confidence
      interval [CI], -3.9 to -0.6), body mass index (-0.6 kg/m(2); 95% CI, -1 to -0.1),
      systolic blood pressure (-1.7 mm Hg; 95% CI, -3.3 to -0.05), diastolic blood
      pressure (-1.5 mm Hg; 95% CI, -2.1 to -0.8), fasting plasma glucose (-3.8 mg/dL,
      95% CI, -7 to -0.6), total cholesterol (-7.4 mg/dL; 95% CI, -10.3 to -4.4), and
      high-sensitivity C-reactive protein (-1.0 mg/L; 95% CI, -1.5 to -0.5). The
      observed heterogeneity across individual trials could, by and large, be
      eliminated by restricting analyses to trials with balanced co-interventions or
      trials with restriction of daily calorie intake in both diet groups. CONCLUSION:
      Mediterranean diets appear to be more effective than low-fat diets in inducing
      clinically relevant long-term changes in cardiovascular risk factors and
      inflammatory markers.

PMID- 21854894
TI  - A prospective observational study of physician handoff for intensive-care-unit-to
      ward patient transfers.
AB  - BACKGROUND: Poor physician handoff can be a major contributor to suboptimal care
      and medical errors occurring in the hospital. Physician handoffs for intensive
      care unit (ICU)-to-ward patient transfer may face more communication hurdles.
      However, few studies have focused on physician handoffs in patient transfers from
      the ICU to the inpatient ward. METHODS: We performed a hospitalized patient-based
      observational study in an urban, university-affiliated tertiary care center to
      assess physician handoff practices for ICU-to-ward patient transfer. One hundred
      twelve adult patients were enrolled. The stakeholders (sending physicians,
      receiving physicians, and patients/families) were interviewed to evaluate the
      quality of communication during these transfers. Data collected included the
      presence and effectiveness of communication, continuity of care, and overall
      satisfaction. RESULTS: During the initial stage of patient transfers, 15.6% of
      the consulted receiving physicians verbally communicated with sending physicians;
      26% of receiving physicians received verbal communication from sending physicians
      when patient transfers occurred. Poor communication during patient transfer
      resulted in 13 medical errors and 2 patients being transiently "lost" to medical
      care. Overall, the levels of satisfaction with communication (scored on a 10
      point scale) for sending physicians, receiving physicians, and patients were
      7.9+/-1.1, 8.1+/-1.0, and 7.9+/-1.7, respectively. CONCLUSION: The overall levels
      of satisfaction with communication during ICU-to-ward patient transfer were
      reasonably high among the stakeholders. However, clear opportunities to improve
      the quality of physician communication exist in several areas, with potential
      benefits to quality of care and patient safety.

PMID- 21854895
TI  - The efficacy of sotalol in preventing postoperative atrial fibrillation: a meta
      analysis.
AB  - OBJECTIVE: Supraventricular tachyarrhythmias including atrial fibrillation are
      common and troubling complications after cardiac surgery, and thus considerable
      interest in pharmacologic prophylaxis has developed. The aim of this study was to
      evaluate the efficacy of sotalol in the prevention of postoperative
      supraventricular tachyarrhythmias. METHODS: Standard methods of meta-analysis
      were used. Randomized clinical trials published in English language were eligible
      for the meta-analysis. RESULTS: A systematic review revealed 15 eligible
      publications that provided 20 comparisons of sotalol with a control group. The
      incidence and relative risk (RR) with 95% confidence interval (CI) of developing
      postoperative supraventricular tachyarrhythmias while taking sotalol were sotalol
      (n=489) versus placebo (n=499): 22.5% versus 41.5%, RR=0.55 (CI, 0.454-0.667,
      P<.001); sotalol (n=304) versus no treatment (n=311): 12% versus 39%, RR=0.329
      (CI, 0.236-0.459, P<.001); sotalol (n=488) versus beta-blocker (n=555): 14%
      versus 23%, RR=0.644 (CI, 0.495-0.838, P<.001); sotalol (n=139) versus amiodarone
      (n=146): no significant differences in supraventricular tachyarrhythmia
      prevention; and sotalol (n=51) versus magnesium (n=54): no significant
      differences in supraventricular tachyarrhythmia prevention. Initiating sotalol
      orally or intravenously had no significant effect on efficacy. Initiating sotalol
      after surgery showed a trend toward less adverse events (before: RR=1.700 [CI,
      0.903-3.200] and after: RR=0.767 [CI, 0.391-1.505]). CONCLUSION: Sotalol is more
      effective in the prevention of supraventricular tachyarrhythmia than placebo or
      beta-blockers. Initiating sotalol before cardiac surgery has no advantage
      compared with initiating sotalol shortly after surgery. Starting sotalol
      intravenously after surgery may be a more reliable method than administering via
      a nasogastric tube or delaying treatment until the patient can take oral
      medication.

PMID- 21854897
TI  - Dancing wheelchairs: an innovative way to teach medical students about
      disability.

PMID- 21854896
TI  - Barriers to non-HDL cholesterol goal attainment by providers.
AB  - PURPOSE: Despite improvements in low-density lipoprotein cholesterol goal
      attainment, non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment
      remains poor. This study assessed providers' knowledge of, attitude toward, and
      practice regarding non-HDL-C. METHODS: Based on a conceptual model, we designed a
      questionnaire that was administered to internal medicine, family practice,
      cardiology, and endocrinology providers attending continuous medical education
      conferences. Responses were compared with those of providers attending a clinical
      lipidology conference. RESULTS: The response rate was 33.3% (354/1063). Among
      providers attending nonlipidology conferences, only 26% knew that non-HDL-C was a
      secondary treatment target, 34% knew non-HDL-C treatment goals, 56% could
      calculate non-HDL-C levels, and 66% knew that non-HDL-C levels could be
      calculated from a standard lipid panel. Compared with providers attending the
      lipidology conference, the other providers were less likely (P<=.01) to have read
      the Adult Treatment Panel III guidelines (46% vs 98%) or to use non-HDL-C (36% vs
      91%). No differences were found between primary care and specialty providers.
      Lack of familiarity with Adult Treatment Panel III guidelines (34%) and of
      knowledge regarding non-HDL-C importance (21%) and calculation (22.7%) were the
      most common barriers identified. CONCLUSIONS: Major gaps remain in providers'
      awareness regarding non-HDL-C definition, calculation, and goals. System-level
      interventions are needed across specialties to address these gaps.

PMID- 21854898
TI  - Invited review: Environmental impacts of dairy processing and products: a review.
AB  - The objective of this review is to summarize research efforts and case studies to
      date of the environmental impacts from dairy processing. The pervasiveness of
      greenhouse gas emission, water use, consumer waste, and other environmental
      impacts of dairy are described. An outline of the method of choice, the life
      cycle assessment, for conducting research and deciding appropriate allocation of
      the impacts is provided. Specific research examples in dairy processing highlight
      how the representative final product is associated with environmental impacts to
      air, water, and land. The primary conclusion from the study was the usefulness of
      life cycle assessment methodology and the need for further research due to
      limited studies, variable data, and the magnitude of environmental impact.

PMID- 21854899
TI  - Influence of mixtures of calcium-chelating salts on the physicochemical
      properties of casein micelles.
AB  - Calcium-chelating salts (CCS), such as phosphates and citrates, are often added
      to milk systems to modify physical properties like heat stability. The objective
      of this study was to investigate the effect of binary CCS mixtures on the
      properties of casein (CN) micelles including the distribution of Ca between the
      soluble and CN-bound states. Six binary CCS mixtures were prepared from 4
      different types of CCS [i.e., trisodium citrate (TSC), disodium phosphate (DSP),
      tetrasodium pyrophosphate (TSPP), and sodium hexameta phosphate (SHMP)] by
      combining 2 CCS at a time in 5 different proportions (8.3:91.7, 29.2:70.8, 50:50,
      70.8:29.2, and 91.7:8.3). Different concentrations of these mixtures (0, 0.1,
      0.3, 0.5, and 0.7% wt/wt) were added to milk protein concentrate solutions (5%
      wt/wt) at pH 5.8. The ability of CCS to disperse CN particles and its interaction
      with Ca were assessed from turbidity measurements, acid-base titration behavior,
      and the quantity of CN-bound Ca and inorganic phosphate (Pi). Turbidity and the
      buffering peak at pH ~5.0 during acid titration decreased with an increasing
      concentration of CCS. This was due to the chelation of Ca and the dispersion of
      CN micelles. The presence of TSC in mixtures decreased the amount of CN-bound Ca
      and Pi; however, the presence of TSPP in mixtures increased CN-bound Ca and Pi.
      When DSP was present at high proportions in mixtures of CCS, the CN-bound Ca and
      Pi slightly increased. When SHMP was used in mixtures of CCS, CN-bound Ca and Pi
      increased with the use of a low proportion of SHMP but decreased when SHMP was
      used at high proportions in the mixture. Combinations of DSP-TSPP used in the
      proportions 29.2:70.8, 50:50, and 70.8:29.2 resulted in the gelation of milk
      protein concentrates when the total CCS concentration was >=0.3%. These results
      indicated that the type of CCS present in a mixture modified CN properties by
      various mechanisms, including chelation of Ca, dispersion of CN micelles, and
      formation of new types of Ca-CCS complexes. The type of interaction between the
      newly formed Ca-CCS complexes and the dispersed CN depended on the proportion,
      concentration, and type of CCS present in the mixtures. This information is
      useful in understanding how mixtures of CCS affect CN properties.

PMID- 21854900
TI  - Effect of selected Hofmeister salts on textural and rheological properties of
      nonfat cheese.
AB  - Three Hofmeister salts (HS; sodium sulfate, sodium thiocyanate, and sodium
      chloride) were evaluated for their effect on the textural and rheological
      properties of nonfat cheese. Nonfat cheese, made by direct acidification, were
      sliced into discs (diameter=50 mm, thickness=2 mm) and incubated with agitation
      (6 h at 22 degrees C) in 50 mL of a synthetic Cheddar cheese aqueous phase buffer
      (pH 5.4). The 3 HS were added at 5 concentrations (0.1, 0.25, 0.5, 0.75, and 1.0
      M) to the buffer. Post-incubation, cheese slices were air dried and equilibrated
      in air-tight bags for 18 h at 5 degrees C before analysis. Small amplitude
      oscillatory rheology properties, including the dynamic moduli and loss tangent,
      were measured during heating from 5 to 85 degrees C. Hardness was determined by
      texture profile analysis. Acid-base buffering was performed to observe changes in
      the indigenous insoluble (colloidal) calcium phosphate (CCP). Moisture content
      decreased with increasing HS concentration. Cheeses incubated in high
      concentrations of SCN(-) softened earlier (i.e., loss tangent=1) compared with
      other HS treatments. Higher melting temperature values were observed for cheeses
      incubated in high concentrations of SO(4)(2-). Hardness decreased in cheeses
      incubated in buffers with high concentrations of SCN(-). The indigenous CCP
      profile of nonfat cheese was not greatly affected by incubation in Cl(-) or SCN(
      ), whereas buffers with high concentrations of SO(4)(2-) reduced the acid-base
      buffering contributed by CCP. The use of high concentrations (1.0M) of SCN(-) for
      incubation of cheeses resulted in a softer protein matrix at high temperatures
      due to the chaotropic effect of SCN(-), which weakened hydrophobic interactions
      between CN. Cheese samples incubated in 1.0M SO(4)(2-) buffers exhibited a
      stiffer protein matrix at high temperatures due to the kosmotropic effect of
      SO(4)(2-), which helped to strengthen hydrophobic interactions in the proteins
      during the heating step. This study showed that HS influenced the texture and
      rheology of nonfat cheese probably by altering the strength of hydrophobic
      interactions between CN.

PMID- 21854901
TI  - Pilot-scale crossflow-microfiltration and pasteurization to remove spores of
      Bacillus anthracis (Sterne) from milk.
AB  - High-temperature, short-time pasteurization of milk is ineffective against spore
      forming bacteria such as Bacillus anthracis (BA), but is lethal to its vegetative
      cells. Crossflow microfiltration (MF) using ceramic membranes with a pore size of
      1.4 MUm has been shown to reject most microorganisms from skim milk; and, in
      combination with pasteurization, has been shown to extend its shelf life. The
      objectives of this study were to evaluate MF for its efficiency in removing
      spores of the attenuated Sterne strain of BA from milk; to evaluate the combined
      efficiency of MF using a 0.8-MUm ceramic membrane, followed by pasteurization (72
      degrees C, 18.6s); and to monitor any residual BA in the permeates when stored at
      temperatures of 4, 10, and 25 degrees C for up to 28 d. In each trial, 95 L of
      raw skim milk was inoculated with about 6.5 log(10) BA spores/mL of milk. It was
      then microfiltered in total recycle mode at 50 degrees C using ceramic membranes
      with pore sizes of either 0.8 MUm or 1.4 MUm, at crossflow velocity of 6.2 m/s
      and transmembrane pressure of 127.6 kPa, conditions selected to exploit the
      selectivity of the membrane. Microfiltration using the 0.8-MUm membrane removed
      5.91+/-0.05 log(10) BA spores/mL of milk and the 1.4-MUm membrane removed 4.50+/
      0.35 log(10) BA spores/mL of milk. The 0.8-MUm membrane showed efficient removal
      of the native microflora and both membranes showed near complete transmission of
      the casein proteins. Spore germination was evident in the permeates obtained at
      10, 30, and 120 min of MF time (0.8-MUm membrane) but when stored at 4 or 10
      degrees C, spore levels were decreased to below detection levels (<=0.3 log(10)
      spores/mL) by d 7 or 3 of storage, respectively. Permeates stored at 25 degrees C
      showed coagulation and were not evaluated further. Pasteurization of the permeate
      samples immediately after MF resulted in additional spore germination that was
      related to the length of MF time. Pasteurized permeates obtained at 10 min of MF
      and stored at 4 or 10 degrees C showed no growth of BA by d 7 and 3,
      respectively. Pasteurization of permeates obtained at 30 and 120 min of MF
      resulted in spore germination of up to 2.42 log(10) BA spores/mL. Spore levels
      decreased over the length of the storage period at 4 or 10 degrees C for the
      samples obtained at 30 min of MF but not for the samples obtained at 120 min of
      MF. This study confirms that MF using a 0.8-MUm membrane before high-temperature,
      short-time pasteurization may improve the safety and quality of the fluid milk
      supply; however, the duration of MF should be limited to prevent spore
      germination following pasteurization.

PMID- 21854902
TI  - Mexican Queso Chihuahua: functional properties of aging cheese.
AB  - Queso Chihuahua, a semi-hard cheese manufactured from raw milk (RM) in northern
      Mexico, is being replaced by pasteurized milk (PM) versions because of food
      safety concerns and the desire for longer shelf life. In this study, the
      functional traits of authentic Mexican Queso Chihuahua made from RM or PM were
      characterized to identify sources of variation and to determine if pasteurization
      of the cheese milk resulted in changes to the functional properties. Two brands
      of RM cheese and 2 brands of PM cheese obtained in 3 seasons of the year from 4
      manufacturers in Chihuahua, Mexico, were analyzed after 0, 4, 8, 12, and 16 wk of
      storage at 4 degrees C. A color measurement spectrophotometer was used to collect
      color data before and after heating at 232 degrees C for 5 min or 130 degrees C
      for 75 min. Meltability was measured using the Schreiber Melt Test on samples
      heated to 232 degrees C for 5 min. Sliceability (the force required to cut
      through a sample) was measured using a texture analyzer fitted with a wire cutter
      attachment. Proteolysis was tracked using sodium dodecyl sulfate-PAGE. Compared
      with PM cheeses, RM cheeses showed less browning upon heating, melted more at 232
      degrees C, and initially required a greater cutting force. With aging, cheeses
      increased in meltability, decreased in whiteness when measured before heating,
      and required less cutting force to slice. Seasonal variations in the cheesemilk
      had minimal or no effect on the functional properties. The differences in the
      functional properties can be attributed, in part, to the mixed microflora present
      in the RM cheeses compared with the more homogeneous microflora added during the
      manufacture of PM cheeses. The degree of proteolysis and subsequent integrity of
      the cheese matrix contribute to melt, slice, and color properties of the RM and
      PM cheeses. Understanding the functional properties of the authentic RM cheeses
      will help researchers and cheesemakers develop pasteurized versions that maintain
      the traditional traits desired in the cheeses.

PMID- 21854903
TI  - Physicochemical, textural, volatile, and sensory profiles of traditional Sepet
      cheese.
AB  - Characterization of traditional cheeses is important for the protection of
      diversity of tradition and contributing baseline data for further research and
      quality control. Sepet cheese is a traditional cheese and specific to the Aegean
      region of Turkey. In this study, 52 Sepet cheese samples were analyzed to
      characterize the physicochemical, textural, volatile compounds, and sensory
      profiles. The changes in the physicochemical and volatile compositions were
      investigated during production and ripening periods. The average dry matter (DM;
      55.16%), fat-in-DM (45.80%), protein (29.18%), salt-in-DM (12.88%), water
      activity (0.83), pH (5.50), titratable acidity (1.69%), ripening and lipolysis
      indices (11.06 and 6.36), firmness (212.20N), springiness (0.62), cohesiveness
      (0.57), adhesiveness (0.48 Nmm), and chewiness (66.87N) values of Sepet cheese
      samples were determined. Hexanoic, octanoic, decanoic, and butyric acids, which
      were responsible for the cheesy, waxy, goaty odors, were the most abundant
      volatile compounds in these cheeses. Most of the volatile compounds increased
      significantly during production and ripening. Significant changes in most of the
      physicochemical characteristics were observed up to the third month of ripening.
      As a result of the descriptive sensory analysis, Sepet cheeses were described
      with descriptors such as free fatty acid, animal like, sulfurous, creamy, cooked,
      and whey, and aromatics with high salty basic taste.

PMID- 21854904
TI  - Genetic diversity in proteolytic enzymes and amino acid metabolism among
      Lactobacillus helveticus strains.
AB  - Lactobacillus helveticus CNRZ 32 is recognized for its ability to decrease
      bitterness and accelerate flavor development in cheese, and has also been shown
      to release bioactive peptides in milk. Similar capabilities have been documented
      in other strains of Lb. helveticus, but the ability of different strains to
      affect these characteristics can vary widely. Because these attributes are
      associated with enzymes involved in proteolysis or AA catabolism, we performed
      comparative genome hybridizations to a CNRZ 32 microarray to explore the
      distribution of genes encoding such enzymes across a bank of 38 Lb. helveticus
      strains, including 2 archival samples of CNRZ 32. Genes for peptidases and AA
      metabolism were highly conserved across the species, whereas those for cell
      envelope-associated proteinases varied widely. Some of the genetic differences
      that were detected may help explain the variability that has been noted among Lb.
      helveticus strains in regard to their functionality in cheese and fermented milk.

PMID- 21854905
TI  - Survival of Listeria monocytogenes introduced as a post-aging contaminant during
      storage of low-salt Cheddar cheese at 4, 10, and 21 degrees C.
AB  - Traditional aged Cheddar cheese does not support Listeria monocytogenes growth
      and, in fact, gradual inactivation of the organism occurs during storage due to
      intrinsic characteristics of Cheddar cheese, such as presence of starter
      cultures, salt content, and acidity. However, consuming high-salt (sodium) levels
      is a health concern and the dairy industry is responding by creating reduced-salt
      cheeses. The microbiological stability of low-salt cheese has not been well
      documented. This study examined the survival of L. monocytogenes in low-salt
      compared with regular-salt Cheddar cheese at 2 pH levels stored at 4, 10, and 21
      degrees C. Cheddar cheeses were formulated at 0.7% and 1.8% NaCl (wt/wt) with
      both low and high pH and aged for 10 wk, resulting in 4 treatments: 0.7% NaCl and
      pH 5.1 (low salt and low pH); 0.7% NaCl and pH 5.5 (low salt and high pH); 1.8%
      NaCl and pH 5.8 (standard salt and high pH); and 1.8% NaCl and pH 5.3 (standard
      salt and low pH). Each treatment was comminuted and inoculated with a 5-strain
      cocktail of L. monocytogenes at a target level of 3.5 log cfu/g, then divided and
      incubated at 4, 10, and 21 degrees C. Survival or growth of L. monocytogenes was
      monitored for up to 90, 90, and 30 d, respectively. Listeria monocytogenes
      decreased by 0.14 to 1.48 log cfu/g in all treatments. At the end of incubation
      at a given temperature, no significant difference existed in L. monocytogenes
      survival between the low and standard salt treatments at either low or high pH.
      Listeria monocytogenes counts decreased gradually regardless of a continuous
      increase in pH (end pH of 5.3 to 6.9) of low-salt treatments at all study
      temperatures. This study demonstrated that post-aging inoculation of L.
      monocytogenes into low-salt (0.7%, wt/wt) Cheddar cheeses at an initial pH of 5.1
      to 5.5 does not support growth at 4, 10, and 21 degrees C up to 90, 90, and 30 d,
      respectively. As none of the treatments demonstrated more than a 1.5 log
      reduction in L. monocytogenes counts, the need for good sanitation practices to
      prevent post-manufacturing cross contamination remains.

PMID- 21854906
TI  - Relationships between milk coagulation property traits analyzed with different
      methodologies.
AB  - Milk coagulation properties (MCP) analysis is performed using a wide range of
      methodologies in different countries and laboratories, using different
      instruments, coagulant activity in the milk, and type of coagulant. This makes it
      difficult to compare results and data from different research. The aims of this
      study were to propose a method for the transformation of values of rennet
      coagulation time (RCT) and curd firmness (a(30)) and to predict the
      noncoagulation (NC) probability of milk samples analyzed using different
      methodologies. Individual milk samples were collected during the morning milking
      in October 2010 from each of 165 Holstein-Friesian dairy cows in 2 freestall
      barns in Italy, and sent to 3 laboratories for MCP analysis. For each laboratory,
      MCP analysis was performed using a different methodology: A, with a computerized
      renneting meter instrument using 0.051 international milk clotting units
      (IMCU)/mL of coagulant activity; B, with a Lattodinamografo (Foss-Italia, Padova,
      Italy) using 0.051 IMCU/mL of coagulant activity; and C, with an Optigraph
      (Ysebaert, Frepillon, France) using 0.120 IMCU/mL of coagulant activity. The
      relationships between MCP traits were analyzed with correlation and regression
      analyses for each pair of methodologies. For each MCP trait, 2 regression models
      were applied: model 1 was a single regression model, where the dependent and
      independent variables were the same MCP trait determined by 2 different
      methodologies; in model 2, both a(30) and RCT were included as independent
      variables. The NC probabilities for laboratories with the highest number of NC
      samples were predicted based on the RCT and a(30) values measured in the
      laboratories with lower number of NC samples using logistic regression and
      receiver operating characteristic analysis. The percentages of NC samples were
      4.2, 11.5, and 0.6% for A, B, and C, respectively. The transformation of MCP
      traits was more precise with model 1 for RCT (R(2): 0.77-0.82) than for a(30)
      (R(2): 0.28-0.63). The application of model 2 was needed when the C measurements
      were transformed into the other scales. The analyses of NC probabilities of milk
      samples showed that NC samples from one methodology were well distinguishable
      (with an accuracy of 0.972-0.996) based on the rennet coagulation time measured
      with the other methodology. A standard definition for MCP traits analysis is
      needed to enable reliable comparisons between MCP traits recorded in different
      laboratories and in different animal populations and breeds.

PMID- 21854907
TI  - Influence of bleaching on flavor of 34% whey protein concentrate and residual
      benzoic acid concentration in dried whey proteins.
AB  - Previous studies have shown that bleaching negatively affects the flavor of 70%
      whey protein concentrate (WPC70), but bleaching effects on lower-protein products
      have not been established. Benzoyl peroxide (BP), a whey bleaching agent,
      degrades to benzoic acid (BA) and may elevate BA concentrations in dried whey
      products. No legal limit exists in the United States for BP use in whey, but
      international concerns exist. The objectives of this study were to determine the
      effect of hydrogen peroxide (HP) or BP bleaching on the flavor of 34% WPC (WPC34)
      and to evaluate residual BA in commercial and experimental WPC bleached with and
      without BP. Cheddar whey was manufactured in duplicate. Pasteurized fat-separated
      whey was subjected to hot bleaching with either HP at 500 mg/kg, BP at 50 or 100
      mg/kg, or no bleach. Whey was ultrafiltered and spray dried into WPC34. Color
      [L*(lightness), a* (red-green), and b* (yellow-blue)] measurements and norbixin
      extractions were conducted to compare bleaching efficacy. Descriptive sensory and
      instrumental volatile analyses were used to evaluate bleaching effects on flavor.
      Benzoic acid was extracted from experimental and commercial WPC34 and 80% WPC
      (WPC80) and quantified by HPLC. The b* value and norbixin concentration of BP
      bleached WPC34 were lower than HP-bleached and control WPC34. Hydrogen peroxide
      bleached WPC34 displayed higher cardboard flavor and had higher volatile lipid
      oxidation products than BP-bleached or control WPC34. Benzoyl peroxide-bleached
      WPC34 had higher BA concentrations than unbleached and HP-bleached WPC34 and BA
      concentrations were also higher in BP-bleached WPC80 compared with unbleached and
      HP-bleached WPC80, with smaller differences than those observed in WPC34. Benzoic
      acid extraction from permeate showed that WPC80 permeate contained more BA than
      did WPC34 permeate. Benzoyl peroxide is more effective in color removal of whey
      and results in fewer flavor side effects compared with HP and residual BA is
      decreased by ultrafiltration and diafiltration.

PMID- 21854908
TI  - Determining salt concentrations for equivalent water activity in reduced-sodium
      cheese by use of a model system.
AB  - The range of sodium chloride (salt)-to-moisture ratio is critical in producing
      high-quality cheese products. The salt-to-moisture ratio has numerous effects on
      cheese quality, including controlling water activity (a(w)). Therefore, when
      attempting to decrease the sodium content of natural cheese it is important to
      calculate the amount of replacement salts necessary to create the same a(w) as
      the full-sodium target (when using the same cheese making procedure). Most
      attempts to decrease sodium using replacement salts have used concentrations too
      low to create the equivalent a(w) due to the differences in the molecular weight
      of the replacers compared with salt. This could be because of the desire to
      minimize off-flavors inherent in the replacement salts, but it complicates the
      ability to conclude that the replacement salts are the cause of off-flavors such
      as bitter. The objective of this study was to develop a model system that could
      be used to measure a(w) directly, without manufacturing cheese, to allow cheese
      makers to determine the salt and salt replacer concentrations needed to achieve
      the equivalent a(w) for their existing full-sodium control formulas. All-purpose
      flour, salt, and salt replacers (potassium chloride, modified potassium chloride,
      magnesium chloride, and calcium chloride) were blended with butter and water at
      concentrations that approximated the solids, fat, and moisture contents of
      typical Cheddar cheese. Salt and salt replacers were applied to the model systems
      at concentrations predicted by Raoult's law. The a(w) of the model samples was
      measured on a water activity meter, and concentrations were adjusted using
      Raoult's law if they differed from those of the full-sodium model. Based on the
      results determined using the model system, stirred-curd pilot-scale batches of
      reduced- and full-sodium Cheddar cheese were manufactured in duplicate. Water
      activity, pH, and gross composition were measured and evaluated statistically by
      linear mixed model. The model system method accurately determined the
      concentrations of salt and salt replacer necessary to achieve the same a(w) as
      the full-sodium control in pilot-scale cheese using different replacement salts.

PMID- 21854909
TI  - The production of intrinsically labeled milk and meat protein is feasible and
      provides functional tools for human nutrition research.
AB  - Administration of labeled, free amino acids does not allow direct assessment of
      in vivo dietary protein digestion and absorption kinetics. Consequently, dietary
      protein sources with labeled amino acids incorporated within their protein matrix
      are required. The aim of the present study was to produce intrinsically L-[1
      (13)C]phenylalanine-labeled milk and meat protein that would permit in vivo
      assessment of postprandial protein digestion and absorption kinetics in humans.
      One lactating dairy cow was continuously infused with 420 MUmol of L-[1
      (13)C]phenylalanine/min for 96 h, with plasma and milk being collected before,
      during, and after isotope infusion. Twenty-four hours after infusion, the cow was
      slaughtered to produce intrinsically labeled meat. Levels of L-[1
      (13)C]phenylalanine enrichment as high as 40 mole percent excess (MPE) in milk
      and 1.5 MPE in meat protein were achieved. In a subsequent human proof-of
      principle experiment, 2 healthy young males (25+/-1 yr; 66.2+/-5.2 kg) each
      ingested 135 g of L-[1-(13)C]phenylalanine intrinsically labeled minced beef,
      after which plasma samples were collected at regular time intervals. Plasma L-[1
      (13)C]phenylalanine enrichments increased during the first 90 min following beef
      ingestion, reaching peak plasma enrichment levels of 0.61+/-0.04 MPE. Whole-body
      net protein balance, assessed by continuous infusion of L-[ring
      (2)H(5)]phenylalanine and L-[ring-(2)H(2)]tyrosine, was higher in the
      postprandial period compared with basal values (6.4+/-0.1 vs. -4.5+/-0.1 MUmol/kg
      per h). In conclusion, the production of intrinsically L-[1-(13)C]phenylalanine
      labeled milk and meat protein is feasible and provides functional tools to
      investigate in vivo protein digestion and absorption kinetics in humans.

PMID- 21854910
TI  - Classification of Swiss cheese starter and adjunct cultures using Fourier
      transform infrared microspectroscopy.
AB  - The acceptability of Swiss cheese largely depends on the flavor profile, and
      strain variations of cheese cultures will affect the final quality. Conventional
      biochemical methods to identify the cultures at the strain level are time
      consuming and expensive, and require skilled labor. Our objective was to develop
      rapid classification methods of starter cultures at the strain level by using a
      combination of hydrophobic grid membrane filters and Fourier transform infrared
      (FTIR) spectroscopy. Forty-four pulsed-field gel electrophoresis-verified strains
      of starter and nonstarter cultures including Streptococcus thermophilus,
      Propionibacterium freudenreichii, and Lactobacillus spp. were analyzed. The
      strains were grown on their respective agar media, transferred to broth media,
      and incubated. Then, cultures were centrifuged and the pellets were resuspended
      in saline solution (10 MUL). Aliquots (2 MUL) of the suspended bacterial solution
      were placed onto a grid of the hydrophobic grid membrane filters, having 6 grids
      per each strain analyzed. The dried filters were read by FTIR microspectroscopy
      fitted with an attenuated total reflectance probe. Collected spectra were
      statistically analyzed by a soft independent modeling of class analogy (SIMCA)
      for pattern recognition. Classification models were developed for Streptococcus
      thermophilus, Propionibacterium freudenreichii, and Lactobacillus spp. strains.
      The models showed major discrimination in the spectral region from 1,200 to 900
      cm(-1) associated with signals from phosphate-containing compounds and various
      polysaccharides in the cell wall. The developed method allowed for rapid
      classification of several Swiss cheese starter and nonstarter cultures at the
      strain level. This information provides a detailed overview of microbiological
      status, which would enable corrective measures to be taken early in the cheese
      making process, limiting production of inferior quality cheese and minimizing
      defects. This method could be an effective tool to identify and monitor activity
      of cheese and other dairy starter cultures.

PMID- 21854911
TI  - Association between somatic cell count and serial locomotion score assessments in
      UK dairy cows.
AB  - This research investigated the effect of lameness, measured by locomotion score
      (LS) on the somatic cell count (SCC) of UK dairy cows. The data set consisted of
      11,141 records of SCC and LS collected monthly on 12 occasions from 1,397 cows
      kept on 7 farms. The data were analyzed to account for the correlation of
      repeated measures of SCC within cow. Results were controlled for farm of origin,
      stage of lactation, parity, season, and test-day milk yield. Compared with the
      geometric mean SCC for cows with LS 1 on each farm, cows on farm 3 with LS 2
      produced milk with 28,000 fewer somatic cells/mL, and cows with LS 2 on farm 6
      produced milk with 30,000 fewer somatic cells/mL at a test day within 10 d. Cows
      that would have LS 3 six months later produced milk with 16,000 fewer somatic
      cells/mL compared with the geometric mean SCC for cows that would have LS 1 in 6
      mo time. These results illustrate differences in disease dynamics between farms,
      highlight potential conflict between lameness and mastitis control measures, and
      emphasize the importance of developing farm-specific estimates of disease costs,
      and hence, health management plans in clinical practice.

PMID- 21854912
TI  - Effect of bioaugmentation on anaerobic wastewater treatment in the dairy
      industry.
AB  - The creation of a biofilm as a specialized biosystem, its development, and
      activity were studied at 3 critical control points of biofilter operation: start
      up, transition from batch to sequencing batch regimen, and set-up of stable
      sequencing batch process. Five variants of biosystems were investigated with an
      inoculum from specially adapted real activated sludge, enriched with various
      combinations of 3 microbial preparations. A stable and working biofilm was
      developed in the phase of stabilized sequencing batch process. The differences
      among biodegradation effectiveness of the 5 variants were insignificant during
      that phase and the effect of the preparations was low. The effectiveness of
      organic removal for the 5 bioaugmentation approaches reached 60% for protein, 70%
      for chemical oxygen demand, and 97% for lactose. Commercial inocula did not
      improve final reactor performance over an inoculum from a municipal wastewater
      treatment plant alone.

PMID- 21854913
TI  - The effects of increased milking frequency during early lactation on milk yield
      and milk composition on commercial dairy farms.
AB  - Increased milking frequency (IMF) during early lactation has the potential for
      carryover responses following the return to normal herd milking frequency. The
      objective was to determine the consistency of response of cows in commercial
      dairy farms to IMF during early lactation. Cows (n=398) were assigned randomly at
      calving within each of the 4 participating farms to 1 of 2 treatments. The
      control group was milked twice-daily (2*) during the entire lactation. The IMF
      group was milked 4-times daily (4*) starting on d 1 to 7, depending on farm,
      until d 21 postcalving and 2* thereafter. Cows in the IMF group were milked at
      the beginning and again at the end of the normal milking routine. Milking
      intervals differed across the farms for the 4* cows with a minimum interval of
      3.5, 4.0, 5.0, and 6h for each of the 4 farms, respectively. The milk yield of
      cows subjected to IMF increased by 2.2+/-0.4 kg/d during the first 7 mo of
      lactation. Interactions of treatment with lactation group (primiparous vs.
      multiparous) were not significant. Although percentages of fat and protein in
      milk were decreased by early lactation IMF (3.69%+/-0.03 fat and 3.05%+/-0.02
      true protein for control vs. 3.57%+/-0.03 fat and 2.99% +/- 0.02 true protein for
      IMF), overall yields of protein were increased by IMF (1.02+/-0.01 vs. 0.98+/
      0.01 kg/d). Early lactation IMF did not affect udder health as assessed by
      somatic cell count linear score. Cows subjected to IMF were 1.4 times more likely
      classified as subclinically ketotic than the control cows. Early lactation IMF
      has the potential to increase milk yield on commercial dairy farms. Although the
      direction of response was the same on all farms, the magnitude of the response
      was different among farms and appears influenced by management practices specific
      to each farm, which included, but were not limited to, housing system, stocking
      density, nutrition, genetics, and other covariates differing among farms.

PMID- 21854914
TI  - Evaluation of somatic cell count thresholds to detect subclinical mastitis in Gyr
      cows.
AB  - The objectives of this study were (1) to determine the sensitivity (Se) and
      specificity (Sp) of somatic cell count (SCC) thresholds to identify subclinical
      mastitis in Gyr cows caused by major and minor pathogens; (2) to study the
      effects of month of sampling, rear or front mammary quarters, herd, intramammary
      infection (IMI), and bacterial species on SCC at quarter level; and (3) to
      describe the prevalence of IMI in Gyr cows in commercial dairy herds. In total,
      221 lactating Gyr cows from 3 commercial dairy farms were selected. Milk samples
      were collected from individual quarters once a month for 1 yr from all lactating
      cows for SCC and bacteriological analysis. Mammary quarters were considered the
      experimental units and the SCC results were log(10)-transformed. Four SCC
      thresholds (100, 200, 300 and 400 * 10(3) cells/mL) were used to determine Se and
      Sp to identify infected mammary quarters. The overall prevalence of IMI in
      quarter milk samples of Gyr cows was 49.8%, and the prevalence of minor pathogens
      was higher (31.9%) than that of major pathogens (17.8%). Quarter samples with
      microbial isolation presented higher SCC compared with negative samples.
      Sensitivity and Sp of selected SCC thresholds varied according to the group of
      pathogen (major and minor) involved in the IMI definition. Sensitivity increased
      and Sp decreased when mammary quarters with only major pathogens isolation were
      considered positive. The use of a single SCC analysis to classify quarters as
      uninfected or infected in Gyr cows may not be a useful test for this breed
      because Se and Sp of SCC at the studied thresholds were low. The occurrence of
      IMI and the bacterial species are the main factors responsible for SCC variation
      in mammary quarters of Gyr cows. Milk samples with major pathogens isolation
      elicited higher SCC than those with minor pathogens.

PMID- 21854915
TI  - Effect of plant oils and camelina expeller on milk fatty acid composition in
      lactating cows fed diets based on red clover silage.
AB  - Five multiparous Finnish Ayrshire cows fed red clover silage-based diets were
      used in a 5 * 5 Latin square with 21-d experimental periods to evaluate the
      effects of various plant oils or camelina expeller on animal performance and milk
      fatty acid composition. Treatments consisted of 5 concentrate supplements
      containing no additional lipid (control), or 29 g/kg of lipid from rapeseed oil
      (RO), sunflower-seed oil (SFO), camelina-seed oil (CO), or camelina expeller
      (CE). Cows were offered red clover silage ad libitum and 12kg/d of experimental
      concentrates. Treatments had no effect on silage or total dry matter intake,
      whole-tract digestibility coefficients, milk yield, or milk composition. Plant
      oils in the diet decreased short- and medium-chain saturated fatty acid (6:0
      16:0) concentrations, including odd- and branched-chain fatty acids and enhanced
      milk fat 18:0 and 18-carbon unsaturated fatty acid content. Increases in the
      relative proportions of cis 18:1, trans 18:1, nonconjugated 18:2, conjugated
      linoleic acid (CLA), and polyunsaturated fatty acids in milk fat were dependent
      on the fatty acid composition of oils in the diet. Rapeseed oil in the diet was
      associated with the enrichment of trans 18:1 (Delta4, 6, 7, 8, and 9), cis-9
      18:1, and trans-7,cis-9 CLA, SFO resulted in the highest concentrations of trans
      5, trans-10, and trans-11 18:1, Delta9,11 CLA, Delta10,12 CLA, and 18:2n-6,
      whereas CO enhanced trans-13-16 18:1, Delta11,15 18:2, Delta12,15 18:2, cis
      9,trans-13 18:2, Delta11,13 CLA, Delta12,14 CLA, Delta13,15 CLA, Delta9,11,15
      18:3, and 18:3n-3. Relative to CO, CE resulted in lower 18:0 and cis-9 18:1
      concentrations and higher proportions of trans-10 18:1, trans-11 18:1, cis
      9,trans-11 CLA, cis-9,trans-13 18:2, and trans-11,cis-15 18:2. Comparison of milk
      fat composition responses to CO and CE suggest that the biohydrogenation of
      unsaturated 18-carbon fatty acids to 18:0 in the rumen was less complete for
      camelina lipid supplied as an expeller than as free oil. In conclusion, moderate
      amounts of plant oils in diets based on red clover silage had no adverse effects
      on silage dry matter intake, nutrient digestion, or milk production, but altered
      milk fat composition, with changes characterized as a decrease in saturated fatty
      acids, an increase in trans fatty acids, and enrichment of specific unsaturated
      fatty acids depending on the fatty acid composition of lipid supplements.

PMID- 21854916
TI  - Automatic recording of daily walkover liveweight of dairy cattle at pasture in
      the first 100 days in milk.
AB  - Daily walkover liveweight (WoLW) records (n=79,697) from 463 pasture-fed dairy
      cows from a single dairy herd in the lower North Island of New Zealand were
      recorded over the first 100 d of lactation. The aims of this study were to (1)
      describe LW records retrieved by a standalone automatic Wo daily weighing system;
      (2) describe the frequency and nature of outlier LW records measured by the
      system and develop an approach for excluding identified outlier LW records; (3)
      quantify the agreement between cow LW measured using the Wo system and those
      measured statically; and (4) describe the autocorrelation between daily LW
      measurements to provide an indication of how frequently management decisions need
      to be reviewed to effectively monitor cow LW change in the early-lactation
      period. The standard deviation of daily LW measurements across parities was 17
      kg, on average. A near perfect association between LW measured statically and
      WoLW (concordance correlation coefficient 0.99, 95% CI 0.99-1.0) was observed.
      After controlling for the effect of LW at calving and long-term LW change using a
      mixed-effects linear regression model, the autocorrelation between WoLW recorded
      on successive days was 0.21, decaying to zero by 8 d. This study shows that by
      using a standalone automatic Wo weighing system positioned in the exit race of a
      rotary milking parlor, it was possible to record LW of individual cows on a daily
      basis and, with controlled cow flow over the weighing platform (allowing for
      sufficient succession distance to prevent congestion), results were similar to
      those recorded using conventional, static weighing techniques using the same
      scales. Based on the autocorrelation analyses, we recommend that LW are recorded
      on a daily basis to allow changes in physiological status such as the onset of
      acute illness or estrus to be detected. For managerial purposes, such as using LW
      change as a guide for adjusting the herd feeding program, we recommend a 7-d
      decision interval to effectively monitor significant changes in cows' recorded
      daily LW measurements.

PMID- 21854917
TI  - The selective treatment of clinical mastitis based on on-farm culture results: I.
      Effects on antibiotic use, milk withholding time, and short-term clinical and
      bacteriological outcomes.
AB  - The objective of this multi-state, multi-herd clinical trial was to evaluate the
      efficacy of using an on-farm culture system to guide strategic treatment
      decisions in cows with clinical mastitis. The study was conducted in 8 commercial
      dairy farms ranging in size from 144 to 1,795 cows from Minnesota, Wisconsin, and
      Ontario, Canada. A total of 422 cows affected with mild or moderate clinical
      mastitis in 449 quarters were randomly assigned to either (1) a positive-control
      treatment program or (2) an on-farm, culture-based treatment program. Quarter
      cases assigned to the positive-control group received immediate on-label
      intramammary treatment with cephapirin sodium. Quarters assigned to the culture
      based treatment program were cultured on-farm and treated with cephapirin sodium
      after 18 to 24h of incubation if they had gram-positive growth or a mixed
      infection. Quarters with gram-negative or no growth did not receive intramammary
      therapy. The proportion of quarter cases assigned to positive-control and culture
      based treatments that received intramammary antibiotic therapy because of study
      assignment was 100 and 44%, respectively; the proportion of cases that received
      secondary antibiotic therapy was 36 and 19%, respectively; and the proportion of
      cases that received intramammary antibiotic therapy because of study assignment
      or secondary therapy was 100 and 51%, respectively. A tendency existed for a
      decrease in the number of days in which milk was discarded from cows assigned to
      the culture-based treatment program versus cows assigned to the positive-control
      group (5.9 vs. 5.2 d). No statistically significant differences existed between
      cases assigned to the positive-control and cases assigned to the culture-based
      treatment program in days to clinical cure (2.7 vs. 3.2 d), bacteriological cure
      risk within 21 d of enrollment (71 vs. 60%), new intramammary infection risk
      within 21 d of enrollment (50 vs. 50%), and treatment failure risk (presence of
      infection, secondary treatment, clinical mastitis recurrence, or removal from
      herd within 21 d after enrollment; 81 vs. 78%). In summary, the use of an on-farm
      culture system to guide the strategic treatment of clinical mastitis reduced
      intramammary antibiotic use by half and tended to decrease milk withholding time
      by 1 d, without significant differences in days to clinical cure, bacteriological
      cure risk, new intramammary infection risk, and treatment failure risk within 21
      d after the clinical mastitis event.

PMID- 21854918
TI  - The selective treatment of clinical mastitis based on on-farm culture results:
      II. Effects on lactation performance, including clinical mastitis recurrence,
      somatic cell count, milk production, and cow survival.
AB  - The objective of this multi-state, multi-herd clinical trial was to report on the
      efficacy of using an on-farm culture system to guide strategic treatment
      decisions in cows with clinical mastitis. The study was conducted in 8 commercial
      dairy farms ranging in size from 144 to 1,795 cows from Minnesota, Wisconsin, and
      Ontario, Canada. A total of 422 cows affected with mild or moderate clinical
      mastitis in 449 quarters were randomly assigned to either (1) a positive-control
      treatment program or (2) an on-farm culture-based treatment program. Quarter
      cases assigned to the positive-control group received immediate on-label
      intramammary treatment with cephapirin sodium. Quarters assigned to the culture
      based treatment program were not treated until the results of on-farm culture
      were determined after 18 to 24h of incubation. Quarters in the culture-based
      treatment program that had gram-positive growth or a mixed infection were treated
      according to label instruction using intramammary cephapirin sodium. Quarters
      assigned to the culture-based treatment program that had gram-negative or no
      growth did not receive intramammary therapy. It was already reported in a
      companion paper that the selective treatment of clinical mastitis based on on
      farm culture results decreases antibiotic use by half and tends to decrease milk
      withholding time without affecting short-term clinical and bacteriological
      outcomes. The present article reports on long-term outcomes of the aforementioned
      study. No statistically significant differences existed between cases assigned to
      the positive-control program and cases assigned to the culture-based treatment
      program in risk and days for recurrence of clinical mastitis in the same quarter
      (35% and 78 d vs. 43% and 82 d), linear somatic cell count (4.2 vs. 4.4), daily
      milk production (30.0 vs. 30.7 kg), and risk and days for culling or death events
      (28% and 160 d vs. 32% and 137 d) for the rest of the lactation after enrollment
      of the clinical mastitis case. In summary, the selective treatment of clinical
      mastitis based on on-farm culture resulted in no differences in long-term
      outcomes, such as recurrence of clinical mastitis in the same quarter, somatic
      cell count, milk production, and cow survival for the rest of the lactation after
      clinical mastitis.

PMID- 21854919
TI  - Lipopolysaccharide challenge of the mammary gland in bovine induced a transient
      glandular shift to anaerobic metabolism.
AB  - Support of milk production in modern dairy cows demands a large proportion of its
      own metabolic resources, such as glucose, which might be required under stressful
      situations. The aim of the experiment was to test the hypothesis that acute
      immune stress shifts oxidative metabolism to glycolysis. Two mammary quarters in
      6 Holstein cows were infused with lipopolysaccharide (LPS), whereas the 2 counter
      quarters served as controls to the treatment. An additional 6 cows were infused
      with saline and served as running controls. The LPS challenge induced dramatic
      transient increases in milk lactate (75-fold) and malate (11-fold) concentrations
      (both markers of glycolysis) at 24h posttreatment. No significant changes in
      lactate and malate concentrations were recorded in control quarters and control
      animals, indicating that the effect of LPS was restricted to the treated gland.
      The LPS challenge induced a dramatic transient decrease in milk yield, and
      lactose and citrate (a marker of mitochondrial metabolism) secretion at 24h
      posttreatment. The kinetics were inversely proportional to those of lactate and
      malate concentrations. Thus, our data suggest that LPS challenge induces acute
      conversion of epithelial cell metabolism from principally mitochondrial-oxidative
      to principally cytosolic (glycolytic), which allows the diversion of metabolic
      resources normally used to synthesize milk to support the immune system. An in
      vitro bacterial growth test showed that concentrations of lactate, malate, and
      lactose equivalent to those found in the in vivo experiment delayed and reduced
      the growth of a pathogenic Escherichia coli strain, suggesting that they play a
      role in diminution of bacterial multiplication in the mammary gland.

PMID- 21854920
TI  - The cost and management of different types of clinical mastitis in dairy cows
      estimated by dynamic programming.
AB  - The objective of this study was to estimate the cost of 3 different types of
      clinical mastitis (CM) (caused by gram-positive bacteria, gram-negative bacteria,
      and other organisms) at the individual cow level and thereby identify the
      economically optimal management decision for each type of mastitis. We made
      modifications to an existing dynamic optimization and simulation model, studying
      the effects of various factors (incidence of CM, milk loss, pregnancy rate, and
      treatment cost) on the cost of different types of CM. The average costs per case
      (US$) of gram-positive, gram-negative, and other CM were $133.73, $211.03, and
      $95.31, respectively. This model provided a more informed decision-making process
      in CM management for optimal economic profitability and determined that 93.1% of
      gram-positive CM cases, 93.1% of gram-negative CM cases, and 94.6% of other CM
      cases should be treated. The main contributor to the total cost per case was
      treatment cost for gram-positive CM (51.5% of the total cost per case), milk loss
      for gram-negative CM (72.4%), and treatment cost for other CM (49.2%). The model
      affords versatility as it allows for parameters such as production costs,
      economic values, and disease frequencies to be altered. Therefore, cost estimates
      are the direct outcome of the farm-specific parameters entered into the model.
      Thus, this model can provide farmers economically optimal guidelines specific to
      their individual cows suffering from different types of CM.

PMID- 21854921
TI  - Evaluation of protocols to synchronize estrus and ovulation in seasonal calving
      pasture-based dairy production systems.
AB  - Lactating dairy cows (n=1,538) were enrolled in a randomized complete block
      design study to evaluate protocols to synchronize estrus and ovulation. Within
      each herd (n=8), cows were divided into 3 calving groups: early, mid, and late,
      based on days in milk (DIM) at mating start date (MSD). Early calving cows
      (n=1,244) were >=42 DIM at MSD, mid-calving cows (n=179) were 21 to 41 DIM at
      MSD, and late-calving cows (n=115) were 0 to 20 DIM at MSD. Cows in the early,
      mid-, and late-calving groups were synchronized to facilitate estrus or timed AI
      (TAI) at MSD (planned breeding 1; PB1), 21 d (PB2), and 42 d (PB3) after MSD,
      respectively. For each PB, cows in the relevant calving group were stratified by
      parity and calving date and randomly assigned to 1 of 4 experimental groups: (1)
      d -10 GnRH (10 MUg of i.m. buserelin) and controlled internal drug release insert
      (CIDR; 1.38 g of progesterone); d -3 PGF(2alpha) (25 mg of i.m. dinoprost); and d
      -2 CIDR out and AI at observed estrus (CIDR_OBS); (2) same as CIDR_OBS, but GnRH
      36 h after CIDR out and TAI 18 h later (CIDR_TAI); (3) same as CIDR_TAI, but no
      CIDR (Ovsynch); or (4) untreated controls (CTRL). The CIDR_OBS, CIDR_TAI, and
      Ovsynch had shorter mean intervals from calving to first service compared with
      the CTRL (69.2, 63.4, and 63.7 vs. 73.7 d, respectively). Both CIDR_OBS
      (predicted probability; PP of pregnancy=0.59) and CIDR_TAI (PP of pregnancy=0.54)
      had increased odds of conceiving at first service compared with Ovsynch [PP of
      pregnancy=0.45; odds ratio (OR)=1.81 and OR=1.46, respectively], and Ovsynch had
      decreased likelihood of conceiving at first service (OR=0.70) compared with CTRL
      (PP of pregnancy=0.53). Both CIDR_TAI hazard ratio; HR [95% confidence
      interval=1.21 (1.04, 1.41)] and Ovsynch [HR (95% confidence interval)=1.23 (1.05,
      1.44)] were associated with an increased likelihood of earlier conception
      compared with the CTRL. A greater proportion of cows on the CIDR_TAI treatment
      successfully established pregnancy in the first 42 d of the breeding season
      compared with the CTRL (0.75 vs. 0.67 PP of 42-d pregnancy, respectively).
      Protocols to synchronize estrus and ovulation were effective at achieving earlier
      first service and conception in pasture-based seasonal calving dairy herds.
      However, animals that conceived following insemination at observed estrus had a
      decreased likelihood of embryo loss to first service compared with animals bred
      with TAI (PP of embryo loss after first service=0.05 vs. 0.09; OR=0.52).

PMID- 21854922
TI  - Quantifying the effect of heat stress on daily milk yield and monitoring dynamic
      changes using an adaptive dynamic model.
AB  - Automation and use of robots are increasingly being used within dairy farming and
      result in large amounts of real time data. This information provides a base for
      the new management concept of precision livestock farming. From 2003 to 2006,
      time series of herd mean daily milk yield were collected on 6 experimental
      research farms in the Netherlands. These time series were analyzed with an
      adaptive dynamic model following a Bayesian method to quantify the effect of heat
      stress. The effect of heat stress was quantified in terms of critical temperature
      above which heat stress occurred, duration of heat stress periods, and resulting
      loss in milk yield. In addition, dynamic changes in level and trend were
      monitored, including the estimation of a weekly pattern. Monitoring comprised
      detection of potential outliers and other deteriorations. The adaptive dynamic
      model fitted the data well; the root mean squared error of the forecasts ranged
      from 0.55 to 0.99 kg of milk/d. The percentages of potential outliers and signals
      for deteriorations ranged from 5.5 to 9.7%. The Bayesian procedure for time
      series analysis and monitoring provided a useful tool for process control. Online
      estimates (based on past and present only) and retrospective estimates
      (determined afterward from all data) of level and trend in daily milk yield
      showed an almost yearly cycle that was in agreement with the calving pattern:
      most cows calved in winter and early spring versus summer and autumn. Estimated
      weekly patterns in terms of weekday effects could be related to specific
      management actions, such as change of pasture during grazing. For the effect of
      heat stress, the mean estimated critical temperature above which heat stress was
      expected was 17.8+/-0.56 degrees C. The estimated duration of the heat stress
      periods was 5.5+/-1.03 d, and the estimated loss was 31.4+/-12.2 kg of milk/cow
      per year. Farm-specific estimates are helpful to identify management factors like
      grazing, housing and feeding, that affect the impact of heat stress. The effect
      of heat stress can be decreased by modifying these factors.

PMID- 21854924
TI  - Effect of lactation number, year, and season of initiation of lactation on milk
      yield of cows hormonally induced into lactation and treated with recombinant
      bovine somatotropin.
AB  - Records representing data from 1,500 barren Holstein cows over an 8-yr period
      from a large commercial dairy farm in northern Mexico were analyzed to determine
      the effects of lactation number and season and year of initiation of lactation on
      milk production of cows induced hormonally into lactation and treated with
      recombinant bovine somatotropin (rbST) throughout lactation. Peak and 305-d milk
      yields were also assessed as predictors of total milk yield in cows induced into
      lactation. A significant quadratic relationship was found between 305-d milk
      yield and number of lactation [7,607+/-145 and 9,548+/-181 kg for first- and >=6
      lactation cows, respectively; mean +/- standard error of the mean (SEM)] with the
      highest production occurring in the fifth lactation. Total milk yields of cows
      with <=2 lactations were approximately 4,500 kg less than milk yields of adult
      cows (the overall average +/- standard milk yield was 13,544+/-5,491 kg per
      lactation and the average lactation length was 454+/-154 d). Moreover, 305-d milk
      production was depressed in cows induced into lactation in spring (8,804+/-153
      kg; mean +/- SEM) and summer (8,724+/-163 kg) than in fall (9,079+/-151 kg) and
      winter (9,085+/-143 kg). Partial regression coefficients for 305-d milk yield and
      peak milk yield indicated an increment of 157 kg of milk per lactation per 1-kg
      increase in peak milk yield (r(2)=0.69). Neither peak milk yield (r(2)=0.18) nor
      305-d milk yield (r(2)=0.29) was accurate for predicting total milk yield per
      lactation. Year, parity, and season effects had significant influence on milk
      yield of cows induced into lactation and treated with rbST throughout lactation,
      and peak milk yield can assist in the prediction of 305-d milk yield but not
      total milk yield. This study also showed that hormonal induction of lactation in
      barren high-yielding cows is a reliable, practical, and affordable technique in
      countries where rbST treatment and prolonged steroid administration of dairy cows
      are legally permitted.

PMID- 21854923
TI  - Hormone-sensitive lipase protein expression and extent of phosphorylation in
      subcutaneous and retroperitoneal adipose tissues in the periparturient dairy cow.
AB  - Lipomobilization is essential for dairy cows to balance the energy requirement
      for milk production in early lactation. This study aimed to determine the role of
      hormone-sensitive lipase (HSL) and its activation by phosphorylation at Ser 660
      (HSLp660) and 563 (HSLp563) in different adipose tissue depots as influenced by
      time and postpartum diet in dairy cows. Biopsy samples were obtained from s.c.
      (SCAT) and retroperitoneal (RPAT) adipose tissues of 20 Holstein cows 21 d
      prepartum, and 1 and 21 d postpartum. After d 1 postpartum, cows were randomly
      assigned to 2 groups (n=10). Groups received diets with either a concentrate-to
      roughage ratio on a dry matter basis of 30:70% (low-concentrate, LC, group) or
      60:40% (high-concentrate group), fed until the third biopsy sampling 21 d
      postpartum. Dry matter intake, milk yield, and milk composition were recorded.
      Blood samples were taken weekly, starting 21 d prepartum and analyzed for
      nonesterified fatty acids, beta-hydroxybutyrate (BHBA), glucose, and insulin.
      Protein expression of HSL and its extent of phosphorylation in adipose tissue
      were measured by semiquantitative Western blotting. Total HSL expression was
      lower in both adipose tissues 1 d after calving compared with prepartum sampling
      (SCAT: 4.10+/-0.5 vs. 2.4+/-0.3; RPAT: 11.1+/-1.3 vs. 6.6+/-1.1). Phosphorylation
      at Ser 660 was higher 21 d postpartum compared with 21 d prepartum in RPAT (2.9+/
      0.3 vs. 4.6+/-0.6). Phosphorylation at Ser 563 was higher 21 d postpartum than 21
      d prepartum in SCAT (0.6+/-0.1 vs. 3.9+/-1.1), and in RPAT a difference was
      observed between 21 d prepartum and 1 d postpartum (1.0+/-0.1 vs. 3.3. +/- 0.6).
      On d 21 postpartum, the LC group showed a lower extent of Ser 563 phosphorylation
      in RPAT (3.9+/-0.8 vs.10.0+/-1.9) and a higher concentration of serum BHBA
      (0.77+/-0.05 vs. 0.47+/-0.11) than did the high-concentrate group. An inhibitory
      influence of higher BHBA concentrations on HSL phosphorylation in the LC group
      could be a possible explanation. On comparing RPAT to SCAT, HSL expression and
      the extent of Ser 660 and 563 phosphorylation was higher in RPAT at 21 d
      prepartum (HSL: 4.1+/-0.5 vs. 11.1+/-1.2; HSLp660 1.3+/-0.2 vs. 2.9+/-0.3;
      HSLp563: 0.6+/-0.1 vs. 1.0+/-0.1). In conclusion, the postpartum feeding regimen
      influenced the phosphorylation pattern, especially in RPAT, implying a regulatory
      role for different phosphorylation sites in adaptive lipolysis of dairy cows. It
      is suggested that RPAT is more sensitive to periparturient challenges than is
      SCAT.

PMID- 21854925
TI  - The relationship between milking interval and somatic cell count in automatic
      milking systems.
AB  - The aim of this study was to explore whether, during automatic milking, milking
      interval or its variation is related to somatic cell count (SCC), even when
      corrected for effects of production, lactation stage, and parity. Data on milking
      interval and production level were available from the automatic milking systems
      of 151 farms. Data on SCC, parity, and lactation stage were derived from dairy
      herd improvement records of the same farms. Mainly due to incomplete records,
      data of 100 farms were used in the final analysis. For every cow, only 1 test day
      was used in the final analysis. Milking interval, the coefficient of variation of
      milking interval, production rate, the difference in production rate between
      short- and long-term, parity, days in milk, and some biologically relevant
      interactions were used in a linear mixed model with farm as random variable to
      assess their association with log10-transformed SCC. None of the interactions was
      significantly related to SCC, whereas all main effects were, and thus, stayed in
      the final model. The effect of milking interval was, although significant, not
      very strong, which shows that the effect of milking interval on SCC is marginal
      when corrected for the other variables. The variation in milking intervals was
      positively related with SCC, showing that the variation in milking interval is
      even more important than the milking interval itself. In the end, this study
      showed only a limited association between milking interval and SCC when milking
      with an automatic milking system.

PMID- 21854926
TI  - Association of conception rate with pattern and level of somatic cell count
      elevation relative to time of insemination in dairy cows.
AB  - The aim was to evaluate the effects of mastitis, determined by the pattern and
      level of somatic cell count (SCC) around first artificial insemination (AI), on
      conception rate (CR). Data from 287,192 first AI and milk records covering a 7-yr
      period were obtained from the Israeli Herd Book. Analyses examined the
      association of probability of conception with SCC elevation relative to timing of
      AI, using generalized linear mixed models. A SCC threshold of 150,000 cells/mL of
      milk was set to distinguish between uninfected cows and cows with mastitis.
      Accordingly, cows with high SCC before and low SCC after AI were designated
      cured, those with low SCC before and high SCC after AI were designated newly
      infected, and cows with high SCC before and after AI were designated chronic
      (likely subclinical) mastitic cows. Compared with uninfected cows, the cured,
      newly infected, and chronic subgroups showed reduced CR (39.4+/-0.1, 36.6+/-0.2,
      32.9+/-0.3, and 31.5+/-0.2, respectively). In the chronic, subclinical group,
      probability of conception was lowered by 14.5% in the mild and moderately
      elevated SCC subgroups and by 20.5% in cows with high SCC elevation compared with
      the uninfected group (CR of 29.7 vs. 39.4%, respectively). A single high
      elevation of SCC (>10(6) cells/mL on only 1 milk test day) lowered the
      probability of conception by 23.6% when it occurred during the 10 d immediately
      before AI, but not when it occurred earlier. For 30 d after AI, probability of
      conception was lowered by about 23%, as reflected in a CR of about 27% compared
      with the uninfected group. Probability of conception was lowered in cows with
      uterine and foot health problems (33.9%), in multiparous cows (34.1%), and in
      cows in the summer (29.1%), but no interactions with mastitis were detected.
      Results indicate that SCC elevation around AI, typical for subclinical mastitis,
      was associated with a significant reduction in probability of conception, and
      that even mild SCC elevation reduced CR. Severe elevation of SCC before AI,
      typical for clinical intramammary infection, reduced the probability of
      conception.

PMID- 21854927
TI  - Glucose transporters and enzymes related to glucose synthesis in small intestinal
      mucosa of mid-lactation dairy cows fed 2 levels of starch.
AB  - Diets containing corn starch may improve glucose supply by providing significant
      amounts of intestinal starch and increasing intestinal glucose absorption in
      dairy cows. Glucose absorption in the small intestine requires specific glucose
      transporters; that is, sodium-dependent glucose co-transporter-1 (SGLT1) and
      facilitated glucose transporter (GLUT2), which are usually downregulated in the
      small intestine of functional ruminants but are upregulated when luminal glucose
      is available. We tested the hypothesis that mRNA and protein expression of
      intestinal glucose transporters and mRNA expression of enzymes related to
      gluconeogenesis are affected by variable starch supply. Dairy cows (n=9/group)
      were fed for 4 wk total mixed rations (TMR) containing either high (HS) or low
      (LS) starch levels in the diet. Feed intake and milk yield were measured daily.
      After slaughter, tissue samples of the small intestinal mucosa (mid-duodenum and
      mid-jejunum) were taken for determination of mRNA concentrations of SGLT1 and
      GLUT2 as well as pyruvate carboxylase, cytosolic phosphoenolpyruvate
      carboxykinase, and glucose-6-phosphatase by real-time reverse transcription PCR
      relative to a housekeeping gene. Protein expression of GLUT2 in crude mucosal
      membranes and of SGLT1 and GLUT2 in brush-border membrane vesicles was quantified
      by sodium dodecyl sulfate-PAGE and immunoblot. A mixed model was used to examine
      feeding and time-related changes on feed intake and milk yield and to test
      feeding and gut site effects on gene or protein expression of glucose
      transporters and enzymes in the intestinal mucosa. Dry matter intake, but not
      energy intake, was higher in cows fed HS compared with LS. Abundance of SGLT1
      mRNA tended to be higher in duodenal than in jejunal mucosa, and mRNA abundances
      of pyruvate carboxylase tended to be higher in jejunal than in duodenal mucosa.
      In brush-border membrane vesicles, SGLT1 and GLUT2 protein expression could be
      demonstrated. No diet-dependent differences were found concerning mRNA and
      protein contents of glucose transporter or mRNA level of gluconeogenic enzymes.
      In conclusion, our investigations on glucose transporters and gluconeogenic
      enzymes in the small intestinal mucosa of dairy cows did not show significant
      diet regulation when TMR with different amounts of intestinal starch were fed.
      Therefore, predicted intestinal glucose absorption after enhanced starch feeding
      is probably not supported by changes of intestinal glucose transporters in dairy
      cows.

PMID- 21854928
TI  - Antimicrobial resistance and prevalence of virulence factor genes in fecal
      Escherichia coli of Holstein calves fed milk with and without antimicrobials.
AB  - Diarrhea in calves has a significant effect on the dairy industry. A common
      management practice for preventing or decreasing the effects of such disease in
      preweaned calves is by the use of antimicrobials in milk or milk replacer. In
      this study, Escherichia coli antimicrobial resistance in fecal samples collected
      from calves 2 to 8 d of age that had or had not received antimicrobials in the
      milk and that had or had not signs of diarrhea by inspection of fecal consistency
      were investigated. Specifically, resistance of E. coli isolates to individual
      antimicrobials, multiresistance patterns, and presence of virulence factors were
      analyzed. Escherichia coli isolates were tested for susceptibility to 12
      antimicrobials by use of a Kirby-Bauer disk diffusion assay. The study was
      conducted at 3 farms, 1 administering growth-promoting antimicrobials (GPA) in
      the milk and 2 not using GPA in the milk (NGPA). All isolates were susceptible to
      ciprofloxacin and cefepime. From the total isolates tested, 84% (n=251) were
      resistant to at least 2 antimicrobials and 81% (n=251) were resistant to 3 or
      more antimicrobials. When antimicrobial resistance was compared between GPA and
      NGPA, it was observed that the GPA group had higher odds of antimicrobial
      resistance for most of the individual antimicrobials tested. No significant
      correlation of virulence factors in GPA or NGPA and diarrheic or non-diarrheic
      (control) fecal samples was found. Of the 32 virulence factors evaluated, 21 were
      detected in the study population; the incidence of only 1 virulence factor was
      statistically significant in each of the diarrheic status (diarrheic or non
      diarrheic) and treatment status (NGPA or GPA) groups. Phylogenetic analysis based
      on the nucleotide sequence of the DNA gyrase gene (gyrB) from 31 fecal E. coli
      isolates revealed 3 main clades.

PMID- 21854929
TI  - Effect of bovine somatotropin administration during induction of lactation in 15
      month-old heifers on production and health.
AB  - Lactation can be induced successfully in 15-mo-old dairy heifers. Treatment of
      heifers induced into lactation with bovine somatotropin (bST) during an
      established lactation improved milk production; however, milk yields were still
      variable. The objective of the present study was to evaluate whether starting bST
      treatment during induction of lactation, rather than after lactation was
      established, would improve milk production beyond that of heifers induced into
      lactation but not treated with bST. Healthy Holstein heifers (n=32, 15 mo of age,
      420+/-28 kg of body weight) were induced into lactation with subcutaneous
      injections of estradiol (0.075 mg/kg of body weight per d) and progesterone (0.25
      mg/kg of body weight per d) for 7 d. Bovine somatotropin (500 mg) was
      administered to heifers (n=16) beginning on experimental d 1 along with the
      estrogen/progesterone treatment. Heifers continued to receive bST every 2 wk for
      10 wk. Control animals (n=16) received no bST during this time. Milking began on
      experimental d 18, and milk production was compared through 53 d in milk
      (experimental d 70). Mean daily milk yield was 36% higher for bST-treated heifers
      than for control animals. A 15.5% difference in milk production between the
      groups was sustained through 305 d of lactation, even after control animals began
      bST treatment at 54 d in milk. Milk fat percentage was similar in bST and control
      heifers. Milk protein percentage was lower in bST-treated heifers (3.58%)
      compared with controls (3.99%) during the treatment comparison period and for the
      remainder of lactation (bST 3.25%, control 3.39%). Heifers treated with bST
      produced more total milk fat and protein compared with controls during the
      treatment comparison period. Throughout the induced lactation, heifers gained
      0.87 kg/d and averaged 2.4 services/pregnancy; 30 became pregnant. Four heifers
      were culled during the induced lactation, and 28 heifers calved at 27.6+/-2.0 mo
      of age for a second lactation. Addition of bST to the lactation induction
      protocol was advantageous because it stimulated greater milk production.

PMID- 21854930
TI  - Short communication: Epidemiology and genotyping of Candida rugosa strains
      responsible for persistent intramammary infections in dairy cows.
AB  - The present study was undertaken during an outbreak of clinical and subclinical
      mastitis in 14 dairy cows caused by Candida rugosa, in which high somatic cell
      counts were seen and cases did not respond to antibiotic treatment. Intramammary
      infection cured spontaneously in 10 cows, whereas 4 cows were culled as a result
      of persistent infections. Repeated sampling of these cows and biomolecular
      analysis of the isolates showed that the infections were caused by the same
      genotype, even over a period of 2 lactations. Random amplification of the genome
      of C. rugosa milk isolates gave 3 different DNA banding patterns (genotypes G1,
      G2, and G3). Viable cells of C. rugosa were also isolated from various
      environmental sources and were present in high concentrations in total mixed
      ration samples, which could be considered the primary source of diffusion of
      viable yeast cells in the environment, as demonstrated by genotyping. The proven
      capacity of these microorganisms to survive in the environment of the cow, such
      as the total mixed ration, bedding, water, and cow skin, and to cause persistent
      intramammary infections highlights the importance of mycotic spread in dairy
      herds.

PMID- 21854931
TI  - Effects of different forage:concentrate ratios in dairy ewe diets supplemented
      with sunflower oil on animal performance and milk fatty acid profile.
AB  - The aim of this study was to evaluate the effect of different forage:concentrate
      (FC) ratios in dairy ewe diets supplemented with sunflower oil (SO) on animal
      performance and milk fatty acid (FA) profile, particularly focusing on trans
      C18:1 FA and conjugated linoleic acid (CLA). Sixty lactating Assaf ewes were
      randomly assigned to 6 treatments in a 3 * 2 factorial arrangement: 3 FC ratios
      (30:70, 50:50, and 70:30) and 2 levels of SO addition (0 and 20 g/kg of dry
      matter). Both the diet FC ratio and SO supplementation affected milk yield, but
      differences between treatments were small. Although the proportion of concentrate
      induced limited changes in milk FA profile, dietary SO significantly decreased
      saturated FA and enhanced total CLA. Furthermore, the incorporation of SO in ewe
      diets decreased the atherogenicity index value by about 25% and doubled the
      contents of potentially healthy FA such as trans-11 C18:1 and cis-9,trans-11 CLA.
      However, the inclusion of SO in a high-concentrate diet (30:70) could switch
      linoleic acid biohydrogenation pathways, resulting in a significant increase in
      trans-10 C18:1, trans-9,cis-11 C18:2, and trans-10,cis-12 C18:2 milk fat
      percentages.

PMID- 21854932
TI  - Isotrichid protozoa influence conversion of glucose to glycogen and other
      microbial products.
AB  - The goal of this in vitro study was to determine the influence of isotrichid
      protozoa (IP) on the conversion of glucose (Glc) to glycogen (Glyc) and
      transformation of Glc into fermentation products. Treatments were ruminal
      inoculum mechanically processed (blended) to destroy IP (B+, verified
      microscopically) or not mechanically processed (B-). Accumulated microbial Glyc
      was measured at 3h of fermentation with (L+; protozoa+bacteria) or without (L-
      predominantly protozoa) lysis of bacterial cells in the fermentation solids with
      0.2 N NaOH. Two 3-h in vitro fermentations were performed using Goering-Van Soest
      medium in batch culture vessels supplemented with 78.75 mg of Glc/vessel in a
      26.5-mL liquid volume. Rumen inoculum from 2 cannulated cows was filtered through
      cheesecloth, combined, and maintained under CO(2) for all procedures. At 3h, 0.63
      and 0.38 mg of Glc remained in B- and B+. Net microbial Glyc accumulation (and
      Glc in Glyc as % of added Glc) detected at 3h of fermentation were 3.32 (4.69%), 
      1.42 (-2.01%), 6.45 (9.10%), and 3.65 (5.15%) mg for B-L-, B+L-, B-L+ and B+L+,
      respectively. Treatments B+ and L+ gave lower Glyc values than B- and L-,
      respectively. Treatment B+L- demonstrated net utilization of alpha-glucan
      contributed by inoculum with no net Glyc production. With destruction of IP,
      total Glyc accumulation declined by 44%, but estimated bacterial Glyc increased.
      Microbial accumulation of N increased 17.7% and calculated CH(4) production
      decreased 24.7% in B+ compared with B-, but accumulation of C in microbes,
      production of organic acids or C in organic acids, calculated CO(2), and
      carbohydrates in cell-free medium did not differ between B+ and B-. Given the
      short 3-h timeframe, increased N accumulation in B+ was attributed to decreased
      Glyc sequestration by IP rather than decreased predation on bacteria. After
      correction for estimates of C from AA and peptides utilized by microbes, 15% of
      substrate Glc C could not be accounted for in measured products in B+ or B-.
      Approximately 30% of substrate Glc was consumed by energetic costs associated
      with Glc transport and Glyc synthesis. The substantial accumulation of Glyc and
      changes in microbial N and Glyc accumulation related to presence of IP suggest
      that these factors should be considered in predicting profiles and amounts of
      microbial products and yield of nutrients to the cow as related to utilization of
      glucose. Determination of applicability of these findings to other soluble
      carbohydrates could be useful.

PMID- 21854933
TI  - The effect of marine algae in the ration of high-yielding dairy cows during
      transition on metabolic parameters in serum and follicular fluid around
      parturition.
AB  - Sixteen Holstein cows were assigned to 2 groups to evaluate the caloric and
      metabolic effect of feeding marine algae (ALG) from 3 wk prepartum until 12 wk
      postpartum. Milk production characteristics and the profiles of hormones and
      metabolites in the serum were monitored from -7 to 46 d in milk (DIM) and in
      follicular fluid (FF) from 14 to 46 DIM. All cows received a corn- and grass
      silage-based partially mixed ration supplemented with concentrate and protein
      supplement. In the diet of the ALG group, 2 kg of the concentrate was replaced by
      a concentrate containing ALG (44 g/d of docosahexaenoic acid). Diets were
      isocaloric (net energy basis) and equal in intestinal digestible protein. The ALG
      diet increased milk yield (41.2 vs. 38.2 kg/d) and decreased milk fat yield
      (1.181 vs. 1.493 kg/d) and milk fat content (31.6 vs. 40.7 g/kg). Protein yield
      (1.336 vs. 1.301 kg/d) was not affected but a tendency toward decreased milk
      protein content (32.8 vs. 34.7 g/kg) was observed. Marine algae supplementation
      increased the beta-hydroxybutyric acid (BHBA) concentration in FF of the ALG cows
      compared with that in the controls (0.992 vs. 0.718 mmol/L). The total protein
      concentration in FF was decreased in ALG (62.9 vs. 67.6 g/L). Plasma and serum
      metabolites did not significantly differ between treatments except for a tendency
      toward a lower concentration of urea in the serum of the control compared with
      ALG (4.69 vs. 5.13 mmol/L). Based on metabolizable energy calculations, a daily
      energy-sparing effect of 3.48 Mcal was obtained due to milk fat depression (MFD).
      The concomitant increase in milk yield suggests that at least part of this spared
      energy is used to stimulate milk production. Theoretically, 3.48 Mcal of ME could
      lead to an increase in milk yield of 7.43 kg/d, which is higher than the observed
      3 kg/d. However, when evaluating nutrient requirements during MFD in early
      lactation, we calculated that increased milk production is caused by a propionate
      saving effect of 2.71 mol in the udder when milk fat is depressed. Concurrent
      increased BHBA concentrations in FF in the ALG group cannot be attributed to a
      worsened energy status of the animals because all other indicators contradict any
      change in energy balance, indicating that BHBA might not be an appropriate
      metabolic parameter to estimate the energy balance in early lactating dairy cows
      during MFD.

PMID- 21854934
TI  - Effects of the addition of direct-fed microbials and glycerol to the diet of
      lactating dairy cows on milk yield and apparent efficiency of yield.
AB  - A study was conducted to evaluate the effects of a direct-fed microbial (M) and
      dietary glycerol (G) on milk yield, efficiency of yield, and nutrient
      digestibility during hot weather. Sixty Holstein cows averaging 120 d in milk
      (DIM) and 36.2 kg/d of milk were used in a 12-wk 2*2 factorial design trial from
      June through September 2008. Cows were fed a common diet during the 2-wk
      standardization period and were blocked by milk yield, DIM, parity, and dry
      matter intake. Diets were based on corn and ryegrass silages and balanced to be
      isocaloric and isonitrogenous. Treatments included a negative control (M- or G-),
      4 * 10(9) cfu/head of a combination of Lactobacillus acidophilus NP51 and
      Propionibacterium freudenreichii NP24 (M+), control plus 400 g/h per day of 99%
      pure food-grade glycerol (G+), and 4*10(9) cfu/h per day of a combination of
      Lactobacillus acidophilus NP51 and Propionibacterium freudenreichii NP24 plus 400
      g/h per day of 99% pure food-grade glycerol (MG++). No interactions were observed
      between direct-fed microbials and dietary glycerol in the study except on
      apparent nutrient digestibility. No differences were observed in dry matter
      intake, which averaged 22.7, 23.1, 23.4, and 22.9 for M-, G-, M+, and G+,
      respectively. Milk yield was increased for M+ compared with M- at 34.1 and 31.7
      kg/d, but G+ had no effect on yield. No treatment effect was noted for milk fat
      percentage or milk protein percentage among diets. Milk protein yield was higher
      for M+ compared with M- at 0.93 versus 0.87 kg/d. Energy-corrected milk was
      improved for the M+ versus M- groups at 33.5 and 31.6 kg/d, respectively. No
      differences in respiratory rate, skin temperature, body temperature, or
      concentrations of serum glucose or urea N were observed among treatments.
      Improvement in apparent digestibility was observed with M+ and G+ compared with M
      /G- in this experiment. The addition of a direct-fed microbial alone improved
      milk and protein yield, energy-corrected milk, and apparent digestibility of
      crude protein, neutral detergent fiber, and acid detergent fiber, and the
      inclusion of glycerol (G+) had a positive effect on apparent dry matter and acid
      detergent fiber digestibility compared with M-/G-. The addition of a direct-fed
      microbial and dietary glycerol may improve yield and digestibility for cows
      subject to heat stress.

PMID- 21854935
TI  - Effects of nutrient restriction on mammary cell turnover and mammary gland
      remodeling in lactating dairy cows.
AB  - The aim of this study was to investigate the effects of a severe nutrient
      restriction on mammary tissue morphology and remodeling, mammary epithelial cell
      (MEC) turnover and activity, and hormonal status in lactating dairy cows. We used
      16 Holstein * Normande crossbred dairy cows, divided into 2 groups submitted to
      different feeding levels (basal and restricted) from 2 wk before calving to wk 11
      postpartum. Restricted-diet cows had lower 11-wk average daily milk yield from
      calving to slaughter than did basal-diet cows (20.5 vs. 33.5 kg/d). Feed
      restriction decreased milk fat, protein, and lactose yields. Restriction also led
      to lower plasma insulin-like growth factor 1 and higher growth hormone
      concentrations. Restricted-diet cows had lighter mammary glands than did basal
      diet cows. The total amount of DNA in the mammary gland and the size of the
      mammary acini were smaller in the restricted-diet group. Feed restriction had no
      significant effect on MEC proliferation at the time of slaughter but led to a
      higher level of apoptosis in the mammary gland. Gelatin zymography highlighted
      remodeling of the mammary extracellular matrix in restricted-diet cows. Udders
      from restricted-diet cows showed lower transcript expression of alpha-lactalbumin
      and kappa-casein. In conclusion, nutrient restriction resulted in lower milk
      yield in lactating dairy cows, partly due to modulation of MEC activity and a
      lower number of mammary cells. An association was found between feed restriction
      induced changes in the growth hormone-insulin-like growth factor-1 axis and
      mammary epithelial cell dynamics.

PMID- 21854936
TI  - Starch source and content in postpartum dairy cow diets: effects on plasma
      metabolites and reproductive processes.
AB  - The objective of this study was to examine the effects of dietary starch source
      and content in the immediate postpartum period on plasma metabolites and hormones
      and ovarian follicular development. One of 3 diets was fed in a randomized block
      design to 40 cows from calving until 70 d in milk. The diets contained 45%
      alfalfa silage (AS), 45% barley silage (BS), or 41% barley silage and 4%
      supplemental starch (SS) on a dry matter basis. All diets contained 45% barley
      based concentrate and 10% alfalfa hay. Resulting starch levels were 25.2, 23.3,
      and 26.7% for AS, BS, and SS, respectively. Body condition was scored every other
      week and dry matter intake and milk yield were recorded daily. Milk samples were
      obtained weekly and blood samples were taken at calving and then every other week
      to determine concentrations of glucose, insulin, insulin-like growth factor-1,
      beta-hydroxybutyrate, and nonesterified fatty acids. Transrectal ultrasonography
      was performed twice per week from 7 d after calving until first ovulation or 62 d
      in milk in all cows. For a subset of 7 AS-, 8 BS-, and 9 SS-fed cows, a complete
      estrous cycle was monitored for ovarian dynamics, and blood samples were
      collected every second day for progesterone and estradiol. Luteinizing hormone
      pulsatility was also determined (5 cows/treatment) approximately 15 d
      postcalving. Treatment had no effect on body condition score, dry matter intake,
      blood metabolites, milk yield, or milk fat and protein contents, but BS-fed cows
      had significantly higher levels of milk urea nitrogen compared with SS cows. Cows
      fed SS (31 d) tended to have a shorter interval from calving to first ovulation
      than cows fed AS (43 d) or BS (38 d). The incidence of double first ovulations
      was higher in cows fed SS (46%) compared with those fed BS (0%). Treatment had no
      effect on LH pulse frequency or amplitude, ovarian dynamics, or progesterone and
      estradiol concentrations during the observed estrous cycle. Energy balance did
      not differ among cows fed the 3 diets. Overall, dietary starch source and
      concentration had little effect on productivity or metabolic status of postpartum
      cows.

PMID- 21854937
TI  - Effects of dietary protein concentration and balance of absorbable amino acids on
      productive responses of dairy cows fed corn silage-based diets.
AB  - A cyclical changeover design experiment (3-wk periods; 12-wk total) was conducted
      to evaluate whether improving the balance of absorbable AA would allow the
      feeding of less crude protein (CP) without compromising production, thereby
      reducing the potential environmental pollution from dairy farms. Sixteen
      multiparous Holstein cows were assigned to 1 of 8 dietary treatments as total
      mixed rations (TMR) containing [dry matter (DM) basis] 45% corn silage, 5%
      coarsely chopped wheat straw, and 50% concentrate mixture. The 8 treatments were
      formulated to differ in dietary CP (14 and 16%; DM basis) and in the balance of
      absorbable AA achieved by changing the main protein source (MPS) of the
      concentrate mixtures [replacing soybean meal (SBM) with corn byproducts (CBP),
      dried corn distillers grains (DDG), and some corn gluten meal], and by adding a
      mixture of rumen-protected Lys and Met (RPLM). Feeding lactating dairy cows corn
      silage-based diets with 16% CP promoted significantly higher DM intakes and milk
      yields, and lower feed N-use efficiency than feeding diets with 14% CP. Replacing
      SBM with CBP significantly increased milk yields and decreased milk fat and
      protein concentrations, but had no effect on the efficiency of conversion of feed
      N into milk N. With 16% CP diets, the addition of RPLM decreased feed N use
      efficiency. A significant effect was observed for the MPS * RPLM interaction on
      milk protein concentrations. Plasma Lys concentration was lower with diets based
      on CBP, and plasma Met increased with RPLM. We did not find clear benefits of
      RPLM in facilitating a reduction of dietary protein without loss of production.

PMID- 21854938
TI  - Modification of milk fatty acid composition by feeding forages and agro
      industrial byproducts from dry areas to Awassi sheep.
AB  - The study tested the hypothesis that certain underused forages and agro
      industrial byproducts available in dry areas may positively influence fatty acid
      (FA) composition and antioxidative properties of milk by their contents of
      residual oil or phenolic compounds or both. Sixty multiparous fat-tailed Awassi
      ewes were allocated to 6 groups in a completely randomized block design. During
      50 d, the ewes were group-fed 2.5 kg of dry matter/d per ewe 1 of 6
      isonitrogenous and isoenergetic diets (forage:concentrate, 0.3:0.7). The test
      feeds, comprising 30% of the diets, replaced either barley straw [lentil straw,
      olive leaves, and Atriplex (saltbush) leaves, rich in phenolic compounds or
      electrolytes] or conventional concentrate ingredients (olive cake and tomato
      pomace; ~10% lipids) from the control diet. The diets containing olive cake and
      tomato pomace were rich in oleic acid (18:1 cis-9; 27% of total dietary FA) and
      linoleic acid (18:2 cis-9,cis-12; 37%), respectively. Profiles of FA were
      determined in individual milk samples drawn on d 0 and in wk 1, 3, 5 and 7. Data
      was analyzed by repeated measurement analysis. No consistent treatment effects on
      yield and gross nutrient composition of the milk were observed, although some
      differences occurred. Milk resulting from the Atriplex leaf diet expressed the
      highest antiradical activity, which was low with control and olive leaves.
      Feeding the tomato pomace and olive cake diets decreased the proportions of short
      and medium-chain FA, whereas oleic acid clearly increased in proportion to total
      FA. Olive leaves most effectively increased rumenic acid (18:2 cis-9,trans-11)
      and alpha-linolenic acid (18:3 cis-9,cis-12,cis-15) in milk fat. This also
      resulted in the highest alpha-linolenic acid transfer rate from feed to milk and
      suggests that olive leaves affect ruminal biohydrogenation at several steps.
      Several alternative feeds exist with an added value, as they enhance FA with
      potential health benefits and the stability of the milk with higher antioxidative
      activity, even though responses to test feeds differed largely. It remains to be
      investigated whether combinations of these feeds would be complementary in these
      beneficial effects.

PMID- 21854939
TI  - Detection of Mycobacterium avium subspecies paratuberculosis in naturally exposed
      dairy heifers and associated risk factors.
AB  - An observational prospective study was conducted to identify risk factors
      associated with fecal shedding of Mycobacterium avium ssp. paratuberculosis (MAP)
      in naturally exposed dairy heifers. The study population consisted of heifers
      from 8 dairy herds in Michigan participating in a MAP control demonstration
      project. Ten heifers from 4 age groups (0 to 3, 4 to 6, 7 to 14, and 15 to 24 mo)
      were selected from each herd every 4 mo for 28 mo and tested for the presence of
      MAP by fecal culture (FC). Heifers from dams testing positive for MAP by serum
      ELISA or FC were preferentially selected, with the remainder of the age cohort
      filled with randomly selected heifers. Logistic regression using generalized
      estimating equations to account for clustering of data within herds and repeated
      measures across heifers was used to evaluate the relationship between MAP FC
      status of heifers and herd risk factors. In total, 1,842 fecal samples were
      collected from 1,202 heifers. Thirty-six (2%) fecal samples, representing 27
      individual heifers, cultured positive for MAP. Heifers shedding MAP were more
      likely to occur in herds with adult-cow MAP ELISA prevalence >10% (odds ratio =
      4.7; 95% confidence interval: 2.0-11.1) and herds milking >300 cows (odds ratio =
      5.7; 95% confidence interval: 2.4-13.4). Mycobacterium avium ssp.
      paratuberculosis can be cultured from the feces of naturally infected dairy
      heifers. The future performance of these MAP FC-positive heifers is unknown and
      needs to be explored.

PMID- 21854941
TI  - Short communication: Feed iodine concentrations on farms with contrasting levels
      of iodine in milk.
AB  - In a previous study, milk iodine concentration from 501 farms across Canada was
      found to vary considerably and appeared to be influenced by feeding practices.
      Farms with contrasting levels of milk iodine from a subset of 200 participating
      farms were used to determine the relationship between milk iodine concentration
      and the concentration of this mineral in different feeds and complete diets given
      to lactating dairy cows. The 30 farms with the lowest levels of iodine in milk
      (low group) and the 30 farms with the highest levels (high group) were selected.
      Samples of bulk tank milk, all feed ingredients, and water were collected.
      Additionally, each farmer completed a questionnaire providing information on
      feeding management. The iodine offered on each of the farms was estimated from
      the amount of the feed in the diet recommended by the Ration'L software (Valacta,
      Ste-Anne-de-Bellevue, QC, Canada) and the iodine concentration in the feed
      sampled and analyzed using inductively coupled plasma mass spectrometry. The
      dietary concentration of iodine offered daily was 33% lower for the low group
      compared with the high group; that is, 1.20+/-0.099 versus 1.81+/-0.195 mg/kg of
      dry matter (DM), respectively. Milk iodine concentrations averaged 146+/-13.9
      MUg/kg for the low group and 487+/-44.6 MUg/kg for the high group. A linear
      relationship was found between dietary iodine concentration and milk iodine
      level, as follows: milk iodine (MUg/kg)=145 (+/-66.9)+113 (+/-39.4) dietary
      iodine concentration (mg/kg DM). However, the low R(2) value (0.15) indicates
      that other factors, such as milking management and the presence of goitrogens,
      may have affected the concentrations of iodine in milk. Forages supplied
      approximately 17% of iodine requirements in the average lactating cow diet.
      Therefore, variations in the iodine content of forages are unlikely to cause
      iodine overfeeding. In contrast, 27% of the mineral mix samples presented iodine
      concentrations >100,000 MUg/kg of DM (and up to 322,000 MUg/kg of DM). More than
      85% of the farms tested were feeding iodine levels higher than the dietary iodine
      recommendations (0.5 mg of iodine/kg of DM). Iodine supplements should be used
      with caution in lactating cow diets.

PMID- 21854940
TI  - Docosahexaenoic acid elevates trans-18:1 isomers but is not directly converted
      into trans-18:1 isomers in ruminal batch cultures.
AB  - Pathways of docosahexaenoic (DHA) biohydrogenation are not known; however, DHA is
      metabolized by ruminal microorganisms. The addition of DHA to the rumen alters
      the fatty acid profile of the rumen and milk and leads to increased trans-18:1
      isomers, particularly trans-11 18:1. This study included 2 in vitro experiments
      to identify if the increase in trans-11 C18:1 was due to DHA being converted into
      trans-11 18:1 or if DHA stimulated trans-11 products from biohydrogenation of
      other fatty acids. In each experiment, ruminal microorganisms collected from a
      lactating Holstein cow were incubated in 10-mL batch cultures for 0, 6, 24, and
      48 h and a uniformly (13)C-labeled DHA was added to the cultures at 0 h as a
      metabolic tracer. Experiment 1 tested 0.5% DHA supplementation and experiment 2
      examined 1, 2, and 3% DHA supplementation to determine if the level of DHA
      effected its conversion into trans-11 18:1. In both experiments, any fatty acid
      that was enriched with the (13)C label was determined to arise from DHA. Palmitic
      (C16:0), stearic (C18:0), all trans-18:1, eicosanoic (C20:0), and docosanoic
      (C22:0) acids were examined for enrichment. In experiment 1, the amount of trans
      18:1 isomers increased 0.415 mg from 0 to 48 h; however, no label was found in
      trans-18:1 at any time. Docosanoic acid was highly enriched at 24h and 48 h to
      20.2 and 16.3%. Low levels of enrichment were found in palmitic and stearic
      acids. In experiment 2, trans-18:1 isomers increased 185, 256, and 272% from 0 to
      48 h when DHA was supplemented at 1, 2, and 3%, respectively; however, as in
      experiment 1, no enrichment occurred of any trans-18:1 isomer. In experiment 2,
      low levels of label were found in palmitic and stearic acids. Enrichment of
      docosanoic acid decreased linearly with increased DHA supplementation. These
      studies showed that trans-18:1 fatty acids are not produced from DHA, supporting
      that DHA elevates trans-18:1 by modifying biohydrogenation pathways of other
      polyunsaturated fatty acids.

PMID- 21854942
TI  - Short communication: Evaluation of milk urea nitrogen as a management tool to
      reduce ammonia emissions from dairy farms.
AB  - The purpose of this study was to compile and evaluate relationships between feed
      nitrogen (N) intake, milk urea N (MUN), urinary urea N (UUN), and ammonia (NH(3))
      emissions from dairy farms to aid policy development. Regression relationships
      between MUN, UUN, and NH(3) emissions were compiled from studies conducted in
      Wisconsin, California, and the Netherlands. Relative reductions in NH(3)
      emissions were calculated as percentage decreases in NH(3) emissions associated
      with a baseline MUN level of 14 mg/dL (prevailing industry average). For 3
      studies with cows in stanchion barns, relative NH(3) emission reductions of 10.3
      to 28.2% were obtained when MUN declined from 14 to 10mg/dL. Similarly, analyses
      of 2 freestall studies provided relative NH(3) emission reductions of 10.5 to
      33.7% when MUN levels declined from 14 to 10mg/dL. The relative reductions in
      NH(3) emissions from both stanchion and freestall barns can be associated
      directly with reductions in UUN excretion, which can be determined using MUN. The
      results of this study may help create new awareness, and perhaps eventual
      industry-based incentives, for management practices that enhance feed N use
      efficiency and reduce MUN, UUN, and NH(3) emissions from dairy farms.

PMID- 21854943
TI  - A whole-genome association analysis of noncompensatory fertility in Holstein
      bulls.
AB  - Increasing fertility in dairy cattle is an important goal. Male infertility
      represents a part of the overall infertility in dairy cattle and can be
      partitioned into compensatory and noncompensatory components, where compensatory
      refers to infertility that can be overcome by increasing sperm number and
      noncompensatory infertility represents the remainder, presumably due to molecular
      and genomic defects. Through estimation of single nucleotide polymorphism (SNP)
      association with noncompensatory bull fertility, it is possible to identify
      regions of the genome influential to this trait. Use of this information in
      selection can allow for an increase in cattle fertility, resulting in economic
      benefits. In this study, high-density SNP genotypes and noncompensatory fertility
      data from 795 Holstein sires were used to examine SNP associations with
      fertility. A Bayes B analysis was performed to develop information for genomic
      selection and to identify genomic regions associated with noncompensatory
      fertility. A cross-validation approach was used to assess the effectiveness of
      the models within the original set of 795 bulls. Correlations of predicted and
      observed fertility values were approximately 0.145 in cross-validation.

PMID- 21854944
TI  - Reliabilities of genomic prediction using combined reference data of the Nordic
      Red dairy cattle populations.
AB  - This study investigated the possibility of increasing the reliability of direct
      genomic values (DGV) by combining reference populations. The data were from 3,735
      bulls from Danish, Swedish, and Finnish Red dairy cattle populations. Single
      nucleotide polymorphism markers were fitted as random variables in a Bayesian
      model, using published estimated breeding values as response variables. In total,
      17 index traits were analyzed. Reliabilities were estimated using a 5-fold cross
      validation, and calculated as the within-year squared correlation between
      estimated breeding values and DGV. Marker effects were estimated using reference
      populations from individual countries, as well as using a combined reference
      population from all 3 countries. Single-country reference populations gave mean
      reliabilities across 17 traits of 0.19 to 0.23, whereas the combined reference
      gave mean reliabilities of 0.26 for all populations. Using marker effects from 1
      population to predict the other 2 gave a loss in mean reliability of 0.14 to 0.21
      when predicting Swedish or Finnish animals with Danish marker effects, or vice
      versa. Using Swedish or Finnish marker effects to predict each other only showed
      a loss in mean reliability of 0.03 to 0.05. A combined Swedish-Finnish reference
      population led to an average reliability as high as that from the 3-country
      reference population, but somewhat different for individual traits. The results
      from this study show that it is possible to increase the reliability of DGV by
      combining reference populations from related populations.

PMID- 21854945
TI  - Genomic breeding value estimation using genetic markers, inferred ancestral
      haplotypes, and the genomic relationship matrix.
AB  - With the introduction of new single nucleotide polymorphism (SNP) chips of
      various densities, more and more genotype data sets will include animals
      genotyped for only a subset of the SNP. Imputation techniques based on unobserved
      ancestral haplotypes may be used to infer missing genotypes. These ancestral
      haplotypes may also be used in the genomic prediction model, instead of using the
      SNP. This may increase the reliability of predictions because the ancestral
      haplotype may capture more linkage disequilibrium with quantitative trait loci
      than SNP. The aim of this paper was to study whether using unobserved ancestral
      haplotypes in a genomic prediction model would provide more reliable genomic
      predictions than using SNP, and to determine how many loci in the genomic
      prediction model would be redundant. Genotypes of 8,960 bulls and cows for 39,557
      SNP were analyzed with a hidden Markov model to associate each individual at each
      locus to 2 ancestral haplotypes. The number of ancestral haplotypes per locus was
      fixed at 10, 15, or 20. Subsequently, a validation study was performed in which
      the phenotypes of 3,251 progeny-tested bulls for 16 traits were used in a genomic
      prediction model to predict the estimated breeding values of at least 753
      validation bulls. The squared correlation between genomic prediction and
      deregressed daughter performance estimated breeding value, when averaged across
      traits, was slightly higher when 15 or 20 ancestral haplotypes per locus were
      used in the prediction model instead of the SNP genotypes, whereas the prediction
      model using a genomic relationship matrix gave the lowest squared correlations.
      The number of redundant loci [i.e., loci that had less than 18 jumps (0.1%) from
      one ancestral haplotype to another ancestral haplotype at the next locus], was
      18,793 (48%), which means that only 20,764 loci would need to be included in the
      genomic prediction model. This provides opportunities for greatly decreasing
      computer requirements of genomic evaluations with very large numbers of markers.

PMID- 21854946
TI  - Variation in residual feed intake in Holstein-Friesian dairy heifers in southern
      Australia.
AB  - Feed conversion efficiency of dairy cattle is an important component of the
      profitability of dairying, given that the cost of feed accounts for much of total
      farm expenses. Residual feed intake (RFI) is a useful measure of feed conversion
      efficiency, as it can be used to compare individuals with the same or differing
      levels of production during the period of measurement. If genetic variation
      exists in RFI among dairy cattle, selection for lower RFI could improve
      profitability. In this experiment, RFI was defined as the difference between an
      animal's actual feed intake and its expected feed intake, which was determined by
      regression of dry matter (DM) intake against mean body weight (BW) and growth
      rate. Nine hundred and three Holstein-Friesian heifer calves, aged between 5 and
      7 mo, were measured for RFI in 3 cohorts of approximately 300 animals. Calves
      were housed under feedlot style conditions in groups of 15 to 20 for 85 to 95 d
      and had ad libitum access to a cubed alfalfa hay. Intakes of individual animals
      were recorded via an electronic feed recording system and BW gain was determined
      by weighing animals once or twice weekly, over a period of 60 to 70 d. Calves had
      DM intake (mean +/- SD) of 8.3+/-1.37 kg of DM/d over the measurement period with
      BW gains of 1.1+/-0.17 kg/d. In terms of converting feed energy for maintenance
      and growth, the 10% most efficient calves (lowest RFI) ate 1.7 kg of DM less each
      day than the 10% least efficient calves (highest RFI) for the same rate of
      growth. Low-RFI heifers also had a significantly lower rate of intake (g/min)
      than high-RFI heifers. The heritability estimate of RFI (mean +/- SE) was 0.27
      (+/-0.12). These results indicate that substantial genetic variation in RFI
      exists, and that the magnitude of this variation is large enough to enable this
      trait to be considered as a candidate trait for future dairy breeding goals. A
      primary focus of future research should be to ensure that calves that are
      efficient at converting feed energy for maintenance and growth also become
      efficient at converting feed energy to milk. Future research will also be
      necessary to identify the consequences of selection for RFI on other traits
      (especially fertility and other fitness traits) and if any interactions exist
      between RFI and feeding level.

PMID- 21854947
TI  - Pedigree analysis and inbreeding effects on calving traits in large dairy herds
      in Germany.
AB  - A pedigree analysis was carried out for a subset of the German Holstein
      population with respect to the effective number of founders and the ancestors
      with the highest effect on 2 defined reference populations. Reference population
      1 contained animals born between 1998 and 2002 (n=19,537), and reference
      population 2 included animals born between 2003 and 2007 (n=19,060). The pedigree
      file included 73,946 animals in total. The effective number of founders was 111.3
      and 92.8 in reference populations 1 and 2, respectively. In reference population
      1, 52.22% of the gene pool could be explained by 10 ancestors. In reference
      population 2, the 10 ancestors with the greatest effect contributed 57.22% of the
      gene pool. The effect of inbreeding on birth weight, calving ease, and stillbirth
      was also analyzed in this study. Two models were used to estimate the effect of
      inbreeding. One model fitted inbreeding as a regression on the inbreeding
      coefficient of the dam, whereas the other model fitted inbreeding as a regression
      on the inbreeding coefficient of the calf. Phenotypic data for this study were
      collected on 3 large commercial milk farms. Data recording took place from
      February 1998 to December 2008 and 36,623 calving events were recorded; 8.19% of
      the calves died at or within 48 h after calving. All calves were weighed after
      birth and the average birth weight was 43 kg for calves born alive and 42 kg for
      stillborn calves. Calving ease was recorded on a scale between 1 and 4. The
      distribution of scores was 69.81, 21.02, 8.96, and 0.22%, ranked 1 (without
      assistance or assistance by 1 person), 2 (assistance by 2 or more persons or
      mechanical assistance), 3 (veterinary assistance), and 4 (operation),
      respectively, on the calving-ease scale. Twins were excluded from all analyses.
      Dam inbreeding had no significant effect on the traits of this study. The
      inbreeding coefficient of the calf had no significant effect on birth weight and
      calving ease but showed a significant effect on stillbirth: the risk of
      stillbirth was found to increase by 0.22% per 1% increase of the inbreeding
      coefficient of the calf.

PMID- 21854948
TI  - Economic effect of short (35-d) compared with conventional (60-d) dry period
      management in commercial Canadian Holstein herds.
AB  - The Canadian dairy industry operates under a supply management system with
      production quotas (expressed in kilograms of butterfat per day) owned by dairy
      producers. Any management strategy influencing production responses must,
      therefore, be evaluated to estimate its effects on quota needed to sell the milk
      produced. In the present study, half of the cows from 13 commercial herds (850
      cows, average of 70 cows per herd) were assigned to be managed for a short dry
      period (SDP; 35 d dry) and the other half was managed for a conventional dry
      period (CDP; 60 d dry) to evaluate the economic impact of a steady state
      involving either CDP or SDP. Economic variables included in the partial budget
      were: variations in revenues from milk and components as well as animals sold;
      costs related to feeding, reproduction, replacement, housing, and treatments. All
      variables were first estimated on a cow basis for each herd individually, and
      average results were used to calculate the partial budget for an average herd.
      Yearly milk and component yields per cow increased, which implies that fewer cows
      are required to produce the same amount of quota. Accordingly, 2 scenarios were
      investigated: in the first one, available quota was kept constant, and herd size
      was adjusted to avoid over-quota production. Consequently, the partial budget was
      calculated considering that 5 fewer cows were present in the herd. In this
      situation, switching to an SDP management increased net annual income for the
      farm by $2,677 (Can$), which represents $41.38 per cow. In the second scenario,
      the number of cows was kept constant, but additional quota (5.5 kg/d, $25,000/kg)
      was bought to allow selling all of the milk produced. In this case, net farm
      income was increased by $17,132 annually with SDP, which represents $245.18 per
      cow. This budget includes interest on the purchase of quota. A comparison of
      partial budgets for individual herds involved in the study revealed considerable
      variation among herds. Switching from a CDP to a SDP management would be
      beneficial for average dairy herds in eastern Canada.

PMID- 21854949
TI  - Survey of dairy housing and manure management practices in California.
AB  - In 2007, a descriptive survey was mailed to all dairies in Glenn (G) and Tulare
      (T) Counties to identify current and future opportunities of manure management
      practices on California dairies. The purpose was to provide baseline information
      for development of outreach curriculum and a decision support tool to quantify
      potential benefits of various N management options on dairy farms. Such baseline
      information is valuable to staff regulating dairy facilities (e.g., San Joaquin
      Valley Unified Air Pollution Control District and Central Valley Regional Water
      Quality Control Board), dairy trade association representatives, and technology
      vendors. Response rates for each county were similar at 29.7% (n=19; G) and 26.7%
      (n=88; T). Mean milking herd size averaged 570 (range 50 to 3,000) cows in G and
      1,800 (range 196 to 9,286) cows in T. Survey data are reported by location due to
      differences between counties in herd size, housing facilities, and climate.
      Freestalls are common housing facilities (63.2%, G; 38.6%, T) and separated
      solids and corral scrapings are commonly used as bedding in freestalls (81.8% G
      and 79.4% T). The most common methods of manure collection were flushing and
      scraping (18.8%, G; 44.7%, T), only flushing (43.8%, G; 34.1%, T), or only
      scraping daily or less frequently than daily (37.5%, G; 20.0%, T). Most dairy
      farms in G (63.2%) and T (70.5%) used some method of separating solids from
      liquids. However, mechanical separation systems alone were used by 5.3% G and
      11.4% T of dairy farms. Storage or treatment ponds were found on 95.9% of
      dairies. Respondents identified existing manure management practices and did not
      indicate any new technologies were in use or being considered for manure
      management. Survey results were used to describe the 2 predominant manure
      management pathways of manure collection, storage, treatment, and utilization.
      Survey results will be used to develop and disseminate targeted information on
      manure treatment technologies, and on-farm evaluation of implemented technologies
      related to anaerobic digesters, solid liquid separation, and pond additives.

PMID- 21854952
TI  - Slow brain oscillations of sleep, resting state, and vigilance.
AB  - The most important quest of cognitive neuroscience may be to unravel the
      mechanisms by which the brain selects, links, consolidates, and integrates new
      information into its neuronal network, while preventing saturation to occur.
      During the past decade, neuroscientists working within several disciplines have
      observed an important involvement of the specific types of brain oscillations
      that occur during sleep--the cortical slow oscillations; during the resting state
      -the fMRI resting state networks including the default-mode network (DMN); and
      during task performance--the performance modulations that link as well to
      modulations in electroencephalography or magnetoencephalography frequency
      content. Understanding the role of these slow oscillations thus appears to be
      essential for our fundamental understanding of brain function. Brain activity is
      characterized by oscillations occurring in spike frequency, field potentials or
      blood oxygen level-dependent functional magnetic resonance imaging signals.
      Environmental stimuli, reaching the brain through our senses, activate or
      inactivate neuronal populations and modulate ongoing activity. The effect they
      sort is to a large extent determined by the momentary state of the slow
      endogenous oscillations of the brain. In the absence of sensory input, as is the
      case during rest or sleep, brain activity does not cease. Rather, its
      oscillations continue and change with respect to their dominant frequencies and
      coupling topography. This chapter briefly introduces the topics that will be
      addressed in this dedicated volume of Progress in Brain Research on slow
      oscillations and sets the stage for excellent papers discussing their molecular,
      cellular, network physiological and cognitive performance aspects. Getting to
      know about slow oscillations is essential for our understanding of plasticity,
      memory, brain structure from synapse to DMN, cognition, consciousness, and
      ultimately for our understanding of the mechanisms and functions of sleep and
      vigilance.

PMID- 21854954
TI  - Involvement of cytokines in slow wave sleep.
AB  - Cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin-1 beta
      (IL1beta) play a role in sleep regulation in health and disease. TNFalpha or
      IL1beta injection enhances non-rapid eye movement sleep. Inhibition of TNFalpha
      or IL1beta reduces spontaneous sleep. Mice lacking TNFalpha or IL1beta receptors
      sleep less. In normal humans and in multiple disease states, plasma levels of
      TNFalpha covary with EEG slow wave activity (SWA) and sleep propensity. Many of
      the symptoms induced by sleep loss, for example, sleepiness, fatigue, poor
      cognition, enhanced sensitivity to pain, are elicited by injection of exogenous
      TNFalpha or IL1beta. IL1beta or TNFalpha applied unilaterally to the surface of
      the cortex induces state-dependent enhancement of EEG SWA ipsilaterally,
      suggesting greater regional sleep intensity. Interventions such as unilateral
      somatosensory stimulation enhance localized sleep EEG SWA, blood flow, and
      somatosensory cortical expression of IL1beta and TNFalpha. State oscillations
      occur within cortical columns. One such state shares properties with whole animal
      sleep in that it is dependent on prior cellular activity, shows homeostasis, and
      is induced by TNFalpha. Extracellular ATP released during neuro- and
      gliotransmission enhances cytokine release via purine type 2 receptors. An ATP
      agonist enhances sleep, while ATP antagonists inhibit sleep. Mice lacking the
      P2X7 receptor have attenuated sleep rebound responses after sleep loss. TNFalpha
      and IL1beta alter neuron sensitivity by changing neuromodulator/neurotransmitter
      receptor expression, allowing the neuron to scale its activity to the presynaptic
      neurons. TNFalpha's role in synaptic scaling is well characterized. Because the
      sensitivity of the postsynaptic neuron is changed, the same input will result in
      a different network output signal and this is a state change. The top-down
      paradigm of sleep regulation requires intentional action from sleep/wake
      regulatory brain circuits to initiate whole-organism sleep. This raises
      unresolved questions as to how such purposeful action might itself be initiated.
      In the new paradigm, sleep is initiated within networks and local sleep is a
      direct consequence of prior local cell activity. Whole-organism sleep is a bottom
      up, self-organizing, and emergent property of the collective states of networks
      throughout the brain.

PMID- 21854955
TI  - Genetic determination of sleep EEG profiles in healthy humans.
AB  - The contribution of slow brain oscillations including delta, theta, alpha, and
      sigma frequencies (0.5-16 Hz) to the sleep electroencephalography (EEG) is finely
      regulated by circadian and homeostatic influences, and reflects functional
      aspects of wakefulness and sleep. Accumulating evidence demonstrates that
      individual sleep EEG patterns in non-rapid-eye-movement (NREM) sleep and rapid
      eye-movement (REM) sleep are heritable traits. More specifically, multiple
      recordings in the same individuals, as well as studies in monozygotic and
      dizygotic twins suggest that a very high percentage of the robust interindividual
      variation and the high intraindividual stability of sleep EEG profiles can be
      explained by genetic factors (> 90% in distinct frequency bands). Still little is
      known about which genes contribute to different sleep EEG phenotypes in healthy
      humans. The genetic variations that have been identified to date include
      functional polymorphisms of the clock gene PER3 and of genes contributing to
      signal transduction pathways involving adenosine (ADA, ADORA2A), brain-derived
      neurotrophic factor (BDNF), dopamine (COMT), and prion protein (PRNP). Some of
      these polymorphisms profoundly modulate sleep EEG profiles; their effects are
      reviewed here. It is concluded that the search for genetic contributions to slow
      sleep EEG oscillations constitutes a promising avenue to identify molecular
      mechanisms underlying sleep-wake regulation in humans.

PMID- 21854956
TI  - Developmental aspects of sleep slow waves: linking sleep, brain maturation and
      behavior.
AB  - Sleep slow waves are the major electrophysiological features of non-rapid eye
      movement (NREM) sleep. Although there is growing understanding of where slow
      waves originate and how they are generated during sleep, the function of slow
      waves is still largely unclear. A recently proposed hypothesis relates slow waves
      to the homeostatic regulation of synaptic plasticity. While several studies
      confirm a correlation between experimentally triggered synaptic changes and slow
      wave activity (SWA), little is known about its association to synaptic changes
      occurring during cortical maturation. Interestingly, slow waves undergo
      remarkable changes during development that parallel the time course of cortical
      maturation. In a recent cross-sectional study including children and adolescents,
      the topographical distribution of SWA was analyzed with high-density
      electroencephalography. The results showed age-dependent differences in SWA
      topography: SWA was highest over posterior regions during early childhood and
      then shifted over central derivations to the frontal cortex in late adolescence.
      This trajectory of SWA topography matches the course of cortical gray maturation.
      In this chapter, the major changes in slow waves during development are
      highlighted and linked to cortical maturation and behavior. Interestingly,
      synaptic density and slow-wave amplitude increase during childhood are highest
      shortly before puberty, decline thereafter during adolescence, reaching overall
      stable levels during adulthood. The question arises whether SWA is merely
      reflecting cortical changes or if it plays an active role in brain maturation. We
      thereby propose a model, by which sleep slow waves may contribute to cortical
      maturation. We hypothesize that while there is a balance between synaptic
      strengthening and synaptic downscaling in adults, the balance of
      strengthening/formation and weakening/elimination is tilted during development.

PMID- 21854953
TI  - Electrophysiological correlates of sleep homeostasis in freely behaving rats.
AB  - The electrical activity of the brain does not only reflect the current level of
      arousal, ongoing behavior, or involvement in a specific task but is also
      influenced by what kind of activity, and how much sleep and waking occurred
      before. The best marker of sleep-wake history is the electroencephalogram (EEG)
      spectral power in slow frequencies (slow-wave activity, 0.5-4 Hz, SWA) during
      sleep, which is high after extended wakefulness and low after consolidated sleep.
      While sleep homeostasis has been well characterized in various species and
      experimental paradigms, the specific mechanisms underlying homeostatic changes in
      brain activity or their functional significance remain poorly understood.
      However, several recent studies in humans, rats, and computer simulations shed
      light on the cortical mechanisms underlying sleep regulation. First, it was found
      that the homeostatic changes in SWA can be fully accounted for by the variations
      in amplitude and slope of EEG slow waves, which are in turn determined by the
      efficacy of corticocortical connectivity. Specifically, the slopes of sleep slow
      waves were steeper in early sleep compared to late sleep. Second, the slope of
      cortical evoked potentials, which is an established marker of synaptic strength,
      was steeper after waking, and decreased after sleep. Further, cortical long-term
      potentiation (LTP) was partially occluded if it was induced after a period of
      waking, but it could again be fully expressed after sleep. Finally, multiunit
      activity recordings during sleep revealed that cortical neurons fired more
      synchronously after waking, and less so after a period of consolidated sleep. The
      decline of all these electrophysiological measures-the slopes of slow waves and
      evoked potentials and neuronal synchrony-during sleep correlated with the decline
      of the traditional marker of sleep homeostasis, EEG SWA. Taken together, these
      data suggest that homeostatic changes in sleep EEG are the result of altered
      neuronal firing and synchrony, which in turn arise from changes in functional
      neuronal connectivity.

PMID- 21854957
TI  - Phasic modulation of cortical high-frequency oscillations by pedunculopontine
      neurons.
AB  - Brain states are dynamically shaped by distinct neuronal systems across the brain
      as a result of an interplay between their intrinsic activity and the
      environmental demand. Subsets of brainstem and forebrain structures influence the
      manifestation of specific brain states (e.g., sleep or wakefulness) and
      contribute to their cyclic alternation. Recent evidence, however, shows that such
      functional partition is not observed in the brainstem, where neuronal
      subpopulations engage in particular patterns of activity that contribute to the
      emergence of phasic components during the cortical slow oscillations. Cholinergic
      neurons of the pedunculopontine nucleus are functionally associated with the
      induction of the waking state but discharge during the phase of the slow
      oscillations that support neuronal activity. Here, we discuss the impact of the
      phasic signals arising from subcortical structures on the modulation of cortical
      slow oscillations and their functional significance.

PMID- 21854958
TI  - Slow oscillations orchestrating fast oscillations and memory consolidation.
AB  - Slow-wave sleep (SWS) facilitates the consolidation of hippocampus-dependent
      declarative memory. Based on the standard two-stage memory model, we propose that
      memory consolidation during SWS represents a process of system consolidation
      which is orchestrated by the neocortical <1Hz electroencephalogram (EEG) slow
      oscillation and involves the reactivation of newly encoded representations and
      their subsequent redistribution from temporary hippocampal to neocortical long
      term storage sites. Indeed, experimental induction of slow oscillations during
      non-rapid eye movement (non-REM) sleep by slowly alternating transcranial current
      stimulation distinctly improves consolidation of declarative memory. The slow
      oscillations temporally group neuronal activity into up-states of strongly
      enhanced neuronal activity and down-states of neuronal silence. In a feed-forward
      efferent action, this grouping is induced not only in the neocortex but also in
      other structures relevant to consolidation, namely the thalamus generating 10
      15Hz spindles, and the hippocampus generating sharp wave-ripples, with the latter
      well known to accompany a replay of newly encoded memories taking place in
      hippocampal circuitries. The feed-forward synchronizing effect of the slow
      oscillation enables the formation of spindle-ripple events where ripples and
      accompanying reactivated hippocampal memory information become nested into the
      single troughs of spindles. Spindle-ripple events thus enable reactivated memory
      related hippocampal information to be fed back to neocortical networks in the
      excitable slow oscillation up-state where they can induce enduring plastic
      synaptic changes underlying the effective formation of long-term memories.

PMID- 21854959
TI  - Spontaneous neural activity during human non-rapid eye movement sleep.
AB  - Recent neuroimaging studies characterized the neural correlates of slow waves and
      spindles during human non-rapid eye movement (NREM) sleep. They showed that
      significant activity was consistently associated with slow (> 140 MUV) and delta
      waves (75-140 MUV) during NREM sleep in several cortical areas including inferior
      frontal, medial prefrontal, precuneus, and posterior cingulate cortices.
      Unexpectedly, slow waves were also associated with transient responses in the
      pontine tegmentum and in the cerebellum. On the other hand, spindles were
      associated with a transient activity in the thalami, paralimbic areas (anterior
      cingulate and insular cortices), and superior temporal gyri. Moreover, slow
      spindles (11-13 Hz) were associated with increased activity in the superior
      frontal gyrus. In contrast, fast spindles (13-15 Hz) recruited a set of cortical
      regions involved in sensorimotor processing, as well as the mesial frontal cortex
      and hippocampus. These findings indicate that human NREM sleep is an active state
      during which brain activity is temporally organized by spontaneous oscillations
      (spindles and slow oscillation) in a regionally specific manner. The functional
      significance of these NREM sleep oscillations is currently interpreted in terms
      of synaptic homeostasis and memory consolidation.

PMID- 21854962
TI  - Hippocampal-cortical interactions and the dynamics of memory trace reactivation.
AB  - The formation of memory and extraction of knowledge from it is the basis of
      intelligence. It is believed that, during slow-wave sleep, the brain reorganizes
      its connectivity matrix so as to store new information optimally. As the
      probability of direct synaptic connection between arbitrarily chosen neurons in
      the cortex is extremely low (on the order of 10(- 6)), a combination of modular
      and hierarchical organization appears to be necessary to enable rapid association
      of arbitrary items. During waking, an "index" of the neural pattern in lower
      order cortical modules may be created and stored in the highest order association
      cortex, the hippocampus, and broadcast back to the relevant cortical modules,
      where it is stored with the local data. In this manner, the pattern can be
      spontaneously reactivated and reinstated in all modules to enable the
      establishment of crossmodular connections, and replay of such patterns of neural
      activity or "phase sequences" has been observed in hippocampus and neocortex. In
      prefrontal cortex, the playback of "phase sequences" is associated with periods
      of intense upstate/downstate transitions and can be accelerated five- to
      eightfold relative to the waking state. The playback speed declines over time as
      does the strength of the replay, which is consistent with a simple decay of an
      asymmetric component of the synaptic weight matrix induced during the experience
      itself. Since the hippocampal events associated with memory reactivation (sharp
      wave ripple events) tend to be correlated with up transitions in the neocortex,
      hippocampus may coordinate reactivation in neocortex, at least under some
      conditions.

PMID- 21854961
TI  - Infraslow (<0.1 Hz) oscillations in thalamic relay nuclei basic mechanisms and
      significance to health and disease states.
AB  - In the absence of external stimuli, the mammalian brain continues to display a
      rich variety of spontaneous activity. Such activity is often highly
      stereotypical, is invariably rhythmic, and can occur with periodicities ranging
      from a few milliseconds to several minutes. Recently, there has been a particular
      resurgence of interest in fluctuations in brain activity occurring at < 0.1 Hz,
      commonly referred to as very slow or infraslow oscillations (ISOs). Whilst this
      is primarily due to the emergence of functional magnetic resonance imaging (fMRI)
      as a technique which has revolutionized the study of human brain dynamics, it is
      also a consequence of the application of full band electroencephalography
      (fbEEG). Despite these technical advances, the precise mechanisms which lead to
      ISOs in the brain remain unclear. In a host of animal studies, one brain region
      that consistently shows oscillations at < 0.1 Hz is the thalamus. Importantly,
      similar oscillations can also be observed in slices of isolated thalamic relay
      nuclei maintained in vitro. Here, we discuss the nature and mechanisms of these
      oscillations, paying particular attention to a potential role for astrocytes in
      their genesis. We also highlight the relationship between this activity and
      ongoing local network oscillations in the alpha (alpha; ~8-13 Hz) band, drawing
      clear parallels with observations made in vivo. Last, we consider the relevance
      of these thalamic ISOs to the pathological activity that occurs in certain types
      of epilepsy.

PMID- 21854960
TI  - Neuronal plasticity and thalamocortical sleep and waking oscillations.
AB  - Throughout life, thalamocortical (TC) network alternates between activated states
      (wake or rapid eye movement sleep) and slow oscillatory state dominating slow
      wave sleep. The patterns of neuronal firing are different during these distinct
      states. I propose that due to relatively regular firing, the activated states
      preset some steady state synaptic plasticity and that the silent periods of slow
      wave sleep contribute to a release from this steady state synaptic plasticity. In
      this respect, I discuss how states of vigilance affect short-, mid-, and long
      term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic
      plasticity. Finally, I suggest that slow oscillation is intrinsic property of
      cortical network and brain homeostatic mechanisms are tuned to use all forms of
      plasticity to bring cortical network to the state of slow oscillation. However,
      prolonged and profound shift from this homeostatic balance could lead to
      development of paroxysmal hyperexcitability and seizures as in the case of brain
      trauma.

PMID- 21854963
TI  - Long-range correlation of the membrane potential in neocortical neurons during
      slow oscillation.
AB  - Large amplitude slow waves are characteristic for the summary brain activity,
      recorded as electroencephalogram (EEG) or local field potentials (LFP), during
      deep stages of sleep and some types of anesthesia. Slow rhythm of the
      synchronized EEG reflects an alternation of active (depolarized, UP) and silent
      (hyperpolarized, DOWN) states of neocortical neurons. In neurons, involvement in
      the generalized slow oscillation results in a long-range synchronization of
      changes of their membrane potential as well as their firing. Here, we aimed at
      intracellular analysis of details of this synchronization. We asked which
      components of neuronal activity exhibit long-range correlations during the
      synchronized EEG? To answer this question, we made simultaneous intracellular
      recordings from two to four neocortical neurons in cat neocortex. We studied how
      correlated is the occurrence of active and silent states, and how correlated are
      fluctuations of the membrane potential in pairs of neurons located close one to
      the other or separated by up to 13 mm. We show that strong long-range correlation
      of the membrane potential was observed only (i) during the slow oscillation but
      not during periods without the oscillation, (ii) during periods which included
      transitions between the states but not during within-the-state periods, and (iii)
      for the low-frequency (< 5 Hz) components of membrane potential fluctuations but
      not for the higher-frequency components (> 10 Hz). In contrast to the neurons
      located several millimeters one from the other, membrane potential fluctuations
      in neighboring neurons remain strongly correlated during periods without slow
      oscillation. We conclude that membrane potential correlation in distant neurons
      is brought about by synchronous transitions between the states, while activity
      within the states is largely uncorrelated. The lack of the generalized fine-scale
      synchronization of membrane potential changes in neurons during the active states
      of slow oscillation may allow individual neurons to selectively engage in short
      living episodes of correlated activity-a process that may be similar to dynamical
      formation of neuronal ensembles during activated brain states.

PMID- 21854965
TI  - Sleep and developmental plasticity not just for kids.
AB  - In a variety of mammalian species, sleep amounts are highest during developmental
      periods of rapid brain development and synaptic plasticity than at any other time
      in life [Frank, M. G. & Heller, H. C. (1997a). Development of REM and slow wave
      sleep in the rat. American Journal of Physiology, 272, R1792-R1799; Jouvet
      Mounier, D., Astic, L., & Lacote, D. (1970). Ontogenesis of the states of sleep
      in rat, cat and guinea pig during the first postnatal month. Developmental
      Psychobiology, 2, 216-239; Roffwarg, H. P., Muzio, J. N., & Dement, W. C. (1966).
      Ontogenetic development of the human sleep-dream cycle. Science, 604-619]. Many
      of the mechanisms governing developmental plasticity also mediate plasticity in
      the adult brain. Therefore, studying the role of sleep in developmental
      plasticity may provide insights more generally into sleep function across the
      lifespan. In this chapter, I review the evidence that supports a critical role
      for sleep in developmental brain plasticity. I begin with an overview of past
      studies that support a role for sleep in general brain maturation. This is
      followed by more recent findings in the developing visual cortex that more
      specifically address a possible role for sleep in cortical plasticity.

PMID- 21854964
TI  - Temporal dynamics of cortical sources underlying spontaneous and peripherally
      evoked slow waves.
AB  - Slow waves are the most prominent electroencephalographic feature of non-rapid
      eye movement (NREM) sleep. During NREM sleep, cortical neurons oscillate
      approximately once every second between a depolarized upstate, when cortical
      neurons are actively firing, and a hyperpolarized downstate, when cortical
      neurons are virtually silent (Destexhe et al., 1999; Steriade et al., 1993a,
      2001). Intracellular recordings indicate that the origins of the slow oscillation
      are cortical and that corticocortical connections are necessary for their
      synchronization (Amzica and Steriade, 1995; Steriade et al., 1993b; Timofeev and
      Steriade, 1996; Timofeev et al., 2000). The currents produced by the near
      synchronous slow oscillation of large populations of neurons appear on the scalp
      as electroencephalogram (EEG) slow waves (Amzica and Steriade, 1997). Despite
      this cellular understanding, questions remain about the role of specific cortical
      structures in individual slow waves. Early EEG studies of slow waves in humans
      were limited by the small number of derivations employed and by the difficulty of
      relating scalp potentials to underlying brain activity (Brazier, 1949; Roth et
      al., 1956). Functional neuroimaging methods offer exceptional spatial resolution,
      but lack the temporal resolution to track individual slow waves (Dang-Vu et al.,
      2008; Maquet, 2000). Intracranial recordings in patient populations are limited
      by the availability of medically necessary electrode placements and can be
      confounded by pathology and medications (Cash et al., 2009; Nir et al., 2011;
      Wenneberg 2010). Source modeling of high-density EEG recordings offers a unique
      opportunity for neuroimaging sleep slow waves. So far, the results have
      challenged several of the influential topographic observations about slow waves
      that had persisted since the original EEG recordings of sleep. These recent
      analyses revealed that individual slow waves are idiosyncratic cortical events
      and that the negative peak of the EEG slow wave often involves cortical
      structures not necessarily apparent from the scalp, like the inferior frontal
      gyrus, anterior cingulate, posterior cingulate, and precuneus (Murphy et al.,
      2009). In addition, not only do slow waves travel (Massimini et al., 2004), but
      they often do so preferentially through the areas comprising the major
      connectional backbone of the human cortex (Hagmann et al., 2008). In this
      chapter, we will review the cellular, intracranial recording, and neuroimaging
      results concerning EEG slow waves. We will also confront a long held belief about
      peripherally evoked slow waves, also known as K-complexes, namely that they are
      modality independent and do not involve cortical sensory pathways. The analysis
      included here is the first to directly compare K-complexes evoked with three
      different stimulation modalities within the same subject on the same night using
      high-density EEG.

PMID- 21854966
TI  - Evoked electrical and cerebral vascular responses during sleep and following
      sleep deprivation.
AB  - Neuronal activity elicits vascular dilation, delivering additional blood and
      metabolites to the activated region. With increasing neural activity, vessels
      stretch and may become less compliant. Most functional imaging studies assume
      that limits to vascular expansion are not normally reached except under
      pathological conditions, with the possibility that metabolism could outpace
      supply. However, we previously demonstrated that evoked hemodynamic responses
      were larger during quiet sleep when compared to both waking and rapid eye
      movement (REM) sleep, suggesting that high basal activity during wake may elicit
      blunted evoked hemodynamic responses due to vascular expansion limits. We
      hypothesized that extended brain activity through sleep deprivation will further
      dilate blood vessels and exacerbate the blunted evoked hemodynamic responses
      observed during wake, and dampen responses in subsequent sleep. We measured
      evoked electrical and hemodynamic responses from rats using auditory clicks
      (0.5s, 10 Hz, 2-13s random ISIs) for 1h following 2, 4, or 6h of sleep
      deprivation. Time-of-day matched controls were recorded continuously for 7h.
      Within quiet sleep periods following deprivation, evoked response potential (ERP)
      amplitude did not differ; however, the evoked vascular response was smaller with
      longer sleep deprivation periods. These results suggest that prolonged neural
      activity periods through sleep deprivation may diminish vascular compliance as
      indicated by the blunted vascular response. Subsequent sleep may allow vessels to
      relax, restoring their ability to deliver blood. These results also suggest that
      severe sleep deprivation or chronic sleep disturbances could push the vasculature
      to critical limits, leading to metabolic deficit and the potential for tissue
      trauma.

PMID- 21854967
TI  - Reduction of nocturnal slow-wave activity affects daytime vigilance lapses and
      memory encoding but not reaction time or implicit learning.
AB  - Total sleep deprivation in healthy subjects has a profound effect on the
      performance on tasks measuring sustained attention or vigilance. We here report
      how a selective disruption of deep sleep only, that is, selective slow-wave
      activity (SWA) reduction, affects the performance of healthy well-sleeping
      subjects on several tasks: a "simple" and a "complex" vigilance task, a
      declarative learning task, and an implicit learning task despite unchanged
      duration of sleep. We used automated electroencephalogram (EEG) dependent
      acoustic feedback aimed at selective interference with-and reduction of-SWA. In a
      within-subject repeated measures crossover design, performance on the tasks was
      assessed in 13 elderly adults without sleep complaints after either SWA-reduction
      or after normal sleep. The number of vigilance lapses increased as a result of
      SWA reduction, irrespective of the type of vigilance task. Recognition on the
      declarative memory task was also affected by SWA reduction, associated with a
      decreased activation of the right hippocampus on encoding (measured with fMRI)
      suggesting a weaker memory trace. SWA reduction, however, did not affect reaction
      time on either of the vigilance tasks or implicit memory task performance. These
      findings suggest a specific role of slow oscillations in the subsequent daytime
      ability to maintain sustained attention and to encode novel declarative
      information but not to maintain response speed or to build implicit memories. Of
      particular interest is that selective SWA reduction can mimic some of the effects
      of total sleep deprivation, while not affecting sleep duration.

PMID- 21854968
TI  - Spectral characteristics of resting state networks.
AB  - Resting state networks (RSNs), as imaged by functional MRI, are distributed maps
      of areas believed to be involved in the function of the "resting" brain, which
      appear in both resting and task data. The current dominant view is that such
      networks are associated with slow (~0.015Hz), spontaneous fluctuations in the
      BOLD signal. To date, limited work has investigated the frequency characteristics
      of RSNs; here we investigate a range of issues relating to their spectral and
      phase characteristics. Our results indicate that RSNs, although dominated by low
      frequencies in the raw BOLD signal, are in fact broadband processes that show
      temporal coherences across a wide frequency spectrum. In addition, we show that
      RSNs exhibit different levels of phase synchrony at different frequencies. These
      findings challenge the notion that FMRI resting signals are simple "low
      frequency" spontaneous signal fluctuations.

PMID- 21854969
TI  - Modulation of the brain's functional network architecture in the transition from
      wake to sleep.
AB  - The transition from quiet wakeful rest to sleep represents a period over which
      attention to the external environment fades. Neuroimaging methodologies have
      provided much information on the shift in neural activity patterns in sleep, but
      the dynamic restructuring of human brain networks in the transitional period from
      wake to sleep remains poorly understood. Analysis of electrophysiological
      measures and functional network connectivity of these early transitional states
      shows subtle shifts in network architecture that are consistent with reduced
      external attentiveness and increased internal and self-referential processing.
      Further, descent to sleep is accompanied by the loss of connectivity in anterior
      and posterior portions of the default-mode network and more locally organized
      global network architecture. These data clarify the complex and dynamic nature of
      the transitional period between wake and sleep and suggest the need for more
      studies investigating the dynamics of these processes.

PMID- 21854971
TI  - Hypnotic modulation of resting state fMRI default mode and extrinsic network
      connectivity.
AB  - Resting state fMRI (functional magnetic resonance imaging) acquisitions are
      characterized by low-frequency spontaneous activity in a default mode network
      (encompassing medial brain areas and linked to self-related processes) and an
      anticorrelated "extrinsic" system (encompassing lateral frontoparietal areas and
      modulated via external sensory stimulation). In order to better determine the
      functional contribution of these networks to conscious awareness, we here sought
      to transiently modulate their relationship by means of hypnosis. We used
      independent component analysis (ICA) on resting state fMRI acquisitions during
      normal wakefulness, under hypnotic state, and during a control condition of
      autobiographical mental imagery. As compared to mental imagery, hypnosis-induced
      modulation of resting state fMRI networks resulted in a reduced "extrinsic"
      lateral frontoparietal cortical connectivity, possibly reflecting a decreased
      sensory awareness. The default mode network showed an increased connectivity in
      bilateral angular and middle frontal gyri, whereas its posterior midline and
      parahippocampal structures decreased their connectivity during hypnosis,
      supposedly related to an altered "self" awareness and posthypnotic amnesia. In
      our view, fMRI resting state studies of physiological (e.g., sleep or hypnosis),
      pharmacological (e.g., sedation or anesthesia), and pathological modulation
      (e.g., coma or related states) of "intrinsic" default mode and anticorrelated
      "extrinsic" sensory networks, and their interaction with other cerebral networks,
      will further improve our understanding of the neural correlates of subjective
      awareness.

PMID- 21854970
TI  - Spontaneous fMRI activity during resting wakefulness and sleep.
AB  - Functional magnetic resonance imaging (fMRI) studies performed during both waking
      rest and sleep show that the brain is continually active in distinct patterns
      that appear to reflect its underlying functional connectivity. In this review,
      potential sources that contribute to spontaneous fMRI activity will be discussed.

PMID- 21854972
TI  - Multimodal neuroimaging in patients with disorders of consciousness showing
      "functional hemispherectomy".
AB  - Beside behavioral assessment of patients with disorders of consciousness,
      neuroimaging modalities may offer objective paraclinical markers important for
      diagnosis and prognosis. They provide information on the structural location and
      extent of brain lesions (e.g., morphometric MRI and diffusion tensor imaging (DTI
      MRI) assessing structural connectivity) but also their functional impact (e.g.,
      metabolic FDG-PET, hemodynamic fMRI, and EEG measurements obtained in "resting
      state" conditions). We here illustrate the role of multimodal imaging in severe
      brain injury, presenting a patient in unresponsive wakefulness syndrome (UWS;
      i.e., vegetative state, VS) and in a "fluctuating" minimally conscious state
      (MCS). In both cases, resting state FDG-PET, fMRI, and EEG showed a functionally
      preserved right hemisphere, while DTI showed underlying differences in structural
      connectivity highlighting the complementarities of these neuroimaging methods in
      the study of disorders of consciousness.

PMID- 21854973
TI  - Roles of multiscale brain activity fluctuations in shaping the variability and
      dynamics of psychophysical performance.
AB  - Spontaneous brain activity across many time scales influences sensory perception
      and human cognitive performance. Empirical insight into the underlying systems
      level mechanisms has, however, remained fragmented. We review here recent studies
      on how wideband scale-free and scale-specific neuronal activity fluctuations
      together bias sensory processing and perceptual performance. We posit that these
      fluctuations constitute the neurophysiological foundation for both the trial-to
      trial behavioral variability and the scaling laws governing psychophysical
      performance.

PMID- 21854974
TI  - Transcription factor loading: please take my place!
AB  - Interactions of transcription factors with chromatin are highly dynamic. Now Voss
      et al. (2011) demonstrate that two transcription factors with identical DNA
      binding specificities do not compete for occupancy at a given DNA element, but
      instead, one factor can even facilitate the binding of another. This assisted
      loading probably involves chromatin-remodeling machines.

PMID- 21854975
TI  - Travel notes from the equatorial circle.
AB  - Accurate chromosome segregation during mitosis and meiosis is essential for cell
      viability. Two papers in this issue of Cell (Kitajima et al., 2011; Magidson et
      al., 2011) describe chromosome movements during cell division with unprecedented
      accuracy, revealing previously unrecognized features of chromosome spindle
      alignment and paving the way to quantitative phenotypic and mechanistic analyses
      of chromosome alignment during prometaphase.

PMID- 21854976
TI  - Elongated membrane zones boost interactions of diffusing proteins.
AB  - Biological membranes are two dimensional, making the discovery of quasi-one
      dimensional diffusion of membrane proteins puzzling. Jaqaman et al. (2011) now
      show that actomyosin and tubulin interact to establish long, thin diffusion
      corridors, thereby increasing the effective concentration of select membrane
      proteins to promote their interactions and modulate signaling.

PMID- 21854977
TI  - Meeting the (N-terminal) end with acetylation.
AB  - Cell-fate decisions are tightly linked to cellular energy status. In this issue,
      Yi et al. (2011) introduce a mechanism by which Bcl-xL lowers the threshold for
      apoptosis by suppressing acetyl-CoA production, which, in turn, suppresses the N
      alpha-acetylation important for activation of the proapoptotic protease caspase
      2.

PMID- 21854978
TI  - Organizing graduate life sciences education around nodes and connections.
AB  - Biomedical education is currently faced with a number of significant challenges,
      including the explosion of information and the need to train researchers who can
      work across traditional disciplinary boundaries. We propose a new integrated
      model for graduate education in the life sciences that addresses these issues.

PMID- 21854979
TI  - Mechanisms for the inheritance of chromatin states.
AB  - Studies in eukaryotes ranging from yeast to mammals indicate that specific
      chromatin structures can be inherited following DNA replication via mechanisms
      acting in cis. Both the initial establishment of such chromatin structures and
      their inheritance require sequence-dependent specificity factors and changes in
      histone posttranslational modifications. Here I propose models for the
      maintenance of epigenetic information in which DNA silencers or nascent RNA
      scaffolds act as sensors that work cooperatively with parentally inherited
      histones to re-establish chromatin states following DNA replication.

PMID- 21854980
TI  - Linking RNA polymerase backtracking to genome instability in E. coli.
AB  - Frequent codirectional collisions between the replisome and RNA polymerase (RNAP)
      are inevitable because the rate of replication is much faster than that of
      transcription. Here we show that, in E. coli, the outcome of such collisions
      depends on the productive state of transcription elongation complexes (ECs).
      Codirectional collisions with backtracked (arrested) ECs lead to DNA double
      strand breaks (DSBs), whereas head-on collisions do not. A mechanistic model is
      proposed to explain backtracking-mediated DSBs. We further show that bacteria
      employ various strategies to avoid replisome collisions with backtracked RNAP,
      the most general of which is translation that prevents RNAP backtracking. If
      translation is abrogated, DSBs are suppressed by elongation factors that either
      prevent backtracking or reactivate backtracked ECs. Finally, termination factors
      also contribute to genomic stability by removing arrested ECs. Our results
      establish RNAP backtracking as the intrinsic hazard to chromosomal integrity and
      implicate active ribosomes and other anti-backtracking mechanisms in genome
      maintenance.

PMID- 21854981
TI  - The spatial arrangement of chromosomes during prometaphase facilitates spindle
      assembly.
AB  - Error-free chromosome segregation requires stable attachment of sister
      kinetochores to the opposite spindle poles (amphitelic attachment). Exactly how
      amphitelic attachments are achieved during spindle assembly remains elusive. We
      employed photoactivatable GFP and high-resolution live-cell confocal microscopy
      to visualize complete 3D movements of individual kinetochores throughout mitosis
      in nontransformed human cells. Combined with electron microscopy, molecular
      perturbations, and immunofluorescence analyses, this approach reveals unexpected
      details of chromosome behavior. Our data demonstrate that unstable lateral
      interactions between kinetochores and microtubules dominate during early
      prometaphase. These transient interactions lead to the reproducible arrangement
      of chromosomes in an equatorial ring on the surface of the nascent spindle. A
      computational model predicts that this toroidal distribution of chromosomes
      exposes kinetochores to a high density of microtubules which facilitates
      subsequent formation of amphitelic attachments. Thus, spindle formation involves
      a previously overlooked stage of chromosome prepositioning which promotes
      formation of amphitelic attachments.

PMID- 21854982
TI  - Complete kinetochore tracking reveals error-prone homologous chromosome
      biorientation in mammalian oocytes.
AB  - Chromosomes must establish stable biorientation prior to anaphase to achieve
      faithful segregation during cell division. The detailed process by which
      chromosomes are bioriented and how biorientation is coordinated with spindle
      assembly and chromosome congression remain unclear. Here, we provide complete 3D
      kinetochore-tracking datasets throughout cell division by high-resolution imaging
      of meiosis I in live mouse oocytes. We show that in acentrosomal oocytes,
      chromosome congression forms an intermediate chromosome configuration, the
      prometaphase belt, which precedes biorientation. Chromosomes then invade the
      elongating spindle center to form the metaphase plate and start biorienting.
      Close to 90% of all chromosomes undergo one or more rounds of error correction of
      their kinetochore-microtubule attachments before achieving correct biorientation.
      This process depends on Aurora kinase activity. Our analysis reveals the error
      prone nature of homologous chromosome biorientation, providing a possible
      explanation for the high incidence of aneuploid eggs observed in mammals,
      including humans.

PMID- 21854983
TI  - Rapid microtubule self-assembly kinetics.
AB  - Microtubule assembly is vital for many fundamental cellular processes. Current
      models for microtubule assembly kinetics assume that the subunit dissociation
      rate from a microtubule tip is independent of free subunit concentration. Total
      Internal-Reflection-Fluorescence (TIRF) microscopy experiments and data from a
      laser tweezers assay that measures in vitro microtubule assembly with nanometer
      resolution, provides evidence that the subunit dissociation rate from a
      microtubule tip increases as the free subunit concentration increases. These data
      are consistent with a two-dimensional model for microtubule assembly, and are
      explained by a shift in microtubule tip structure from a relatively blunt shape
      at low free concentrations to relatively tapered at high free concentrations. We
      find that because both the association and the dissociation rates increase at
      higher free subunit concentrations, the kinetics of microtubule assembly are an
      order-of-magnitude higher than currently estimated in the literature.

PMID- 21854984
TI  - Cytoskeletal control of CD36 diffusion promotes its receptor and signaling
      function.
AB  - The mechanisms that govern receptor coalescence into functional clusters--often a
      critical step in their stimulation by ligand--are poorly understood. We used
      single-molecule tracking to investigate the dynamics of CD36, a clustering
      responsive receptor that mediates oxidized LDL uptake by macrophages. We found
      that CD36 motion in the membrane was spatially structured by the cortical
      cytoskeleton. A subpopulation of receptors diffused within linear confinement
      regions whose unique geometry simultaneously facilitated freedom of movement
      along one axis while increasing the effective receptor density. Co-confinement
      within troughs enhanced the probability of collisions between unligated receptors
      and promoted their clustering. Cytoskeleton perturbations that inhibited
      diffusion in linear confinement regions reduced receptor clustering in the
      absence of ligand and, following ligand addition, suppressed CD36-mediated
      signaling and internalization. These observations demonstrate a role for the
      cytoskeleton in controlling signal transduction by structuring receptor diffusion
      within membrane regions that increase their collision frequency.

PMID- 21854985
TI  - Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell
      survival.
AB  - Previous experiments suggest a connection between the N-alpha-acetylation of
      proteins and sensitivity of cells to apoptotic signals. Here, we describe a
      biochemical assay to detect the acetylation status of proteins and demonstrate
      that protein N-alpha-acetylation is regulated by the availability of acetyl-CoA.
      Because the antiapoptotic protein Bcl-xL is known to influence mitochondrial
      metabolism, we reasoned that Bcl-xL may provide a link between protein N-alpha
      acetylation and apoptosis. Indeed, Bcl-xL overexpression leads to a reduction in
      levels of acetyl-CoA and N-alpha-acetylated proteins in the cell. This effect is
      independent of Bax and Bak, the known binding partners of Bcl-xL. Increasing
      cellular levels of acetyl-CoA by addition of acetate or citrate restores protein
      N-alpha-acetylation in Bcl-xL-expressing cells and confers sensitivity to
      apoptotic stimuli. We propose that acetyl-CoA serves as a signaling molecule that
      couples apoptotic sensitivity to metabolism by regulating protein N-alpha
      acetylation.

PMID- 21854986
TI  - Structural linkage between ligand discrimination and receptor activation by type
      I interferons.
AB  - Type I Interferons (IFNs) are important cytokines for innate immunity against
      viruses and cancer. Sixteen human type I IFN variants signal through the same
      cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different
      physiological effects. The crystal structures of two human type I IFN ternary
      signaling complexes containing IFNalpha2 and IFNomega reveal recognition modes
      and heterotrimeric architectures that are unique among the cytokine receptor
      superfamily but conserved between different type I IFNs. Receptor-ligand cross
      reactivity is enabled by conserved receptor-ligand "anchor points" interspersed
      among ligand-specific interactions that "tune" the relative IFN-binding
      affinities, in an apparent extracellular "ligand proofreading" mechanism that
      modulates biological activity. Functional differences between IFNs are linked to
      their respective receptor recognition chemistries, in concert with a ligand
      induced conformational change in IFNAR1, that collectively control signal
      initiation and complex stability, ultimately regulating differential STAT
      phosphorylation profiles, receptor internalization rates, and downstream gene
      expression patterns.

PMID- 21854987
TI  - Stochastic state transitions give rise to phenotypic equilibrium in populations
      of cancer cells.
AB  - Cancer cells within individual tumors often exist in distinct phenotypic states
      that differ in functional attributes. While cancer cell populations typically
      display distinctive equilibria in the proportion of cells in various states, the
      mechanisms by which this occurs are poorly understood. Here, we study the
      dynamics of phenotypic proportions in human breast cancer cell lines. We show
      that subpopulations of cells purified for a given phenotypic state return towards
      equilibrium proportions over time. These observations can be explained by a
      Markov model in which cells transition stochastically between states. A
      prediction of this model is that, given certain conditions, any subpopulation of
      cells will return to equilibrium phenotypic proportions over time. A second
      prediction is that breast cancer stem-like cells arise de novo from non-stem-like
      cells. These findings contribute to our understanding of cancer heterogeneity and
      reveal how stochasticity in single-cell behaviors promotes phenotypic equilibrium
      in populations of cancer cells.

PMID- 21854989
TI  - SnapShot: Dendritic Cells.

PMID- 21854990
TI  - Enhancing the patient position in the world of health care: contributions from
      the EACH conference 2010 in Verona.

PMID- 21854988
TI  - The human mitochondrial transcriptome.
AB  - The human mitochondrial genome comprises a distinct genetic system transcribed as
      precursor polycistronic transcripts that are subsequently cleaved to generate
      individual mRNAs, tRNAs, and rRNAs. Here, we provide a comprehensive analysis of
      the human mitochondrial transcriptome across multiple cell lines and tissues.
      Using directional deep sequencing and parallel analysis of RNA ends, we
      demonstrate wide variation in mitochondrial transcript abundance and precisely
      resolve transcript processing and maturation events. We identify previously
      undescribed transcripts, including small RNAs, and observe the enrichment of
      several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI
      footprinting, we establish the global profile of DNA-binding protein occupancy
      across the mitochondrial genome at single-nucleotide resolution, revealing
      regulatory features at mitochondrial transcription initiation sites and
      functional insights into disease-associated variants. This integrated analysis of
      the mitochondrial transcriptome reveals unexpected complexity in the regulation,
      expression, and processing of mitochondrial RNA and provides a resource for
      future studies of mitochondrial function (accessed at
      http://mitochondria.matticklab.com).

PMID- 21854991
TI  - Home care for cancer patients after an earthquake: the experience of the
      "L'Aquila per la Vita" Home Care Unit.

PMID- 21854992
TI  - Intolerance to mirtazapine in advanced cancer.

PMID- 21854993
TI  - Ketamine infusion for sickle cell crisis pain in an adult.

PMID- 21854994
TI  - Suffering and spirituality: analysis of living experiences.

PMID- 21854996
TI  - The Lombard effect.

PMID- 21854997
TI  - Coprinopsis cinerea.

PMID- 21854998
TI  - Neural basis of mathematical cognition.
AB  - The human brain has remarkable capabilities for encoding and manipulating
      information about quantities. Understanding how the brain carries out such number
      and quantity processing is a problem not just for those interested in numerical
      cognition: it raises important questions that are relevant to understanding
      development, action, vision, language, executive function and cortical
      organisation. It is also a clear case of research into a core human psychological
      function having indisputable everyday relevance; hence the emphasis in early
      education on numeracy and later on mathematics.

PMID- 21854999
TI  - Genetic detection of mislabeled fish from a certified sustainable fishery.

PMID- 21855000
TI  - Endosymbiosis: bacteria sharing the load.
AB  - A nested set of bacterial endosymbionts within mealybug cells collectively
      provides amino acids to their host, but their genomes show that some pathways are
      distributed between both endosymbionts, while other essential proteins are
      missing altogether. The possibility that additional functions are shared between
      partners warrants comparisons with organelles.

PMID- 21855001
TI  - Metabolism: what causes the gut's circadian instincts?
AB  - What mechanisms control circadian rhythms in the gastrointestinal tract and how
      does this impact nutrient metabolism? The deadenylase and leucine zipper protein
      Nocturnin is now shown to play a central role.

PMID- 21855002
TI  - Yeast mating: trying out new pickup lines.
AB  - Mating of Ascomycete fungi involves chemically distinct pheromones; one partner
      makes a lipid-modified peptide, the other partner a simple peptide. A new study
      has now found that this inherent asymmetry may not be necessary.

PMID- 21855004
TI  - Oogenesis: active heterochromatin.
AB  - The genome of Drosophila is protected from DNA damage during oogenesis by a
      mechanism involving short RNAs. Surprisingly transcription of these RNAs requires
      that their DNA is associated with a histone modification usually associated with
      gene silencing.

PMID- 21855003
TI  - Bacterial cell wall: thinking globally, actin locally.
AB  - The bacterial actin-like protein MreB is thought to form a continuous helical
      polymer at the membrane to confer rod shape. Two new studies now show that MreB
      forms discrete dynamic patches that travel circumferentially.

PMID- 21855005
TI  - Sensory transduction: the 'swarm intelligence' of auditory hair bundles.
AB  - In vertebrate hair cells, the hair bundle is responsible for the conversion of
      mechanical vibrations into electrical signals. In a combined experimental and
      computational tour de force, a group of researchers now presents a quantitative
      model that explains how the bundle's specific microarchitecture gives rise to its
      exquisite mechanosensory properties.

PMID- 21855006
TI  - Chromosome segregation: monopolin attracts condensin.
AB  - To segregate chromosomes properly, the cell must prevent merotely, an error that
      occurs when a single kinetochore is attached to microtubules emanating from both
      spindle poles. Recent evidence suggests that cooperation between Pcs1/Mde4 and
      condensin complexes plays an important role in preventing merotely.

PMID- 21855007
TI  - Circadian rhythms: FLOWERING LOCUS T extends opening hours.
AB  - Plants are more sensitive to light in the day than at night due to the circadian
      clock. The protein that acts downstream from the clock to modulate blue light
      signalling in stomata comes as a surprise; it is FT, which is thought to be the
      long-distance regulator of flowering.

PMID- 21855008
TI  - DNA replication: mammalian Treslin-TopBP1 interaction mirrors yeast Sld3-Dpb11.
AB  - There are many parallels between DNA replication in yeast and humans. Now, two
      recent studies extend this relationship by dissecting key conserved interactions
      necessary for initiation of the replisome.

PMID- 21855009
TI  - Looking towards the next 25 years.

PMID- 21855010
TI  - Commentary. A combination of statins and beta-blockers is independently
      associated with a reduction in the incidence of perioperative mortality and
      nonfatal myocardial infarction in patients undergoing abdominal aortic aneurysm
      surgery.

PMID- 21855011
TI  - Reprinted article "Prospective randomised study of endovenous radiofrequency
      obliteration (closure) versus ligation and vein stripping (EVOLVeS): two-year
      follow-up".
AB  - PURPOSE: To study intermediate clinical outcomes, rates of recurrent varicosities
      and neovascularisation, ultrasound changes of the GSV, and the quality of life
      changes in patients from EVOLVeS trial. METHODS: Forty five patients were re
      examined 1 year and 65 two years after treatment. Follow-up visits included
      clinical examination with CEAP classification and calculation of venous clinical
      severity score (VCSS), ultrasound examination, and a quality of life
      questionnaire. RESULTS: The clinical course of the disease (CEAP, VCSS) was
      similar in the two treatment groups. 51% of the GSV trunks occluded by RFO
      underwent progressive shrinkage with the external diameter decreased from 6.3 SD
      1.4 mm at 72 h after treatment to 2.9 SD 1.5 mm at 2 years. An additional 41% of
      the GSV became undetectable by ultrasound at 2-year follow up. In two patients we
      observed re-opening of an initially closed GSV lumen. Neovascularisation was
      found in one RFO case and in four S and L cases. Cumulative rates of recurrent
      varicose veins at combined 1 and 2 years follow-up were 14% for RFO and 21% for S
      and L (NS). The difference in global QOL score in favour of RFO re-appeared at 1
      year and remained significant at 2 years after treatment. CONCLUSION: The 2-year
      clinical results of radiofrequency obliteration are at least equal to those after
      high ligation and stripping of the GSV. In the vast majority of RFO patients the
      GSV remained permanently closed, and underwent progressive shrinkage to eventual
      sonographic disappearance. Recurrence and neovascularisation rates were similar
      in the two groups although limited patient numbers prevent reliable statistical
      analysis. Improved quality of life scores persisted through the 2-year
      observations in the RFO group compared to the S and L group.

PMID- 21855012
TI  - Commentary. Prospective randomised study of endovenous radiofrequency
      obliteration (closure) versus ligation and vein stripping (EVOLVeS): two-year
      follow-up.

PMID- 21855013
TI  - Commentary. Subintimal angioplasty of femoropopliteal artery occlusions: the long
      term results.

PMID- 21855014
TI  - Reprinted article "Pathophysiology of vein graft failure: a review".
AB  - Vein bypass grafting is an integral component of cardiovascular surgical practice
      for both arterial and venous diseases. However, many of these grafts will
      eventually fail due to either intrinsic or extrinsic causes. This review examines
      the current understanding and knowledge of venous histology, vein graft pathology
      and the associated endothelial and smooth muscle cell physiology and
      pharmacology. In addition, the status of research on the therapeutic control of
      vein graft intimal hyperplasia and accelerated atherosclerosis is assessed.

PMID- 21855015
TI  - In the beginning...

PMID- 21855016
TI  - Commentary. Pathophysiology of vein graft failure: a review.

PMID- 21855018
TI  - Commentary. Carotid artery plaque composition--relationship to clinical
      presentation and ultrasound B-mode imaging.

PMID- 21855017
TI  - Reprinted article "Carotid artery plaque composition--relationship to clinical
      presentation and ultrasound B-mode imaging".
AB  - OBJECTIVE: To correlate B-mode ultrasound findings to carotid plaque histology.
      DESIGN: European multicentre study (nine centres). MATERIAL AND METHODS: Clinical
      presentation and risk factors were recorded and preoperative ultrasound Duplex
      scanning with special emphasis on B-mode imaging studies was performed in 270
      patients undergoing carotid endarterectomy. Perioperatively, macroscopic plaque
      features were evaluated and the removed specimens were analysed histologically
      for fibrous tissue, calcification and 'soft tissue' (primarily haemorrhage and
      lipid). RESULTS: Males had more soft tissue than females (p = 0.0006),
      hypertensive patients less soft tissue than normotensive (p = 0.01) and patients
      with recent symptoms more soft tissue than patients with earlier symptoms (p =
      0.004). There was no correlation between surface description on ultrasound images
      compared to the surface judged intraoperatively by the surgeon. Echogenicity on B
      mode images was inversely related to soft tissue (p = 0.005) and calcification
      was directly related to echogenicity (p < 0.0001). Heterogeneous plaques
      contained more calcification than homogeneous (p = 0.003), however, there was no
      difference in content of soft tissue. CONCLUSION: Ultrasound B-mode
      characteristics are related to the histological composition of carotid artery
      plaques and to patient's history. These results may imply that patients with
      distant symptoms may be regarded and treated as asymptomatic patients whereas
      asymptomatic patients with echolucent plaques should be considered for carotid
      endarterectomy.

PMID- 21855019
TI  - Reprinted article "The fate of the claudicant--a prospective study of 1969
      claudicants".
AB  - A prospective study of 1969 patients with intermittent claudication receiving
      placebo medication for a minimum of 1 year is reported. Patients were carefully
      monitored and only four patients were lost to follow-up. Annual mortality was
      4.3%. Thirty-six patients developed a definite myocardial infarction, 27 a major
      stroke, 32 required a major amputation and 111 required surgical or radiological
      intervention for deteriorating ischaemia of the leg. The entry characteristics of
      the patients were analysed as a predictor of serious cardiovascular events. The
      most sensitive predictors of total mortality were age, history of coronary heart
      disease and an ankle/arm pressure ratio below 0.5. Of the laboratory measurements
      performed only the initial white cell count was a significant predictor of
      myocardial infarction, stroke and vascular deaths.

PMID- 21855020
TI  - Reprinted article "Exercise training versus angioplasty for stable claudication.
      Long and medium term results of a prospective, randomised trial".
AB  - OBJECTIVES: To compare percutaneous transluminal angioplsty (PTA) against
      exercise training in the treatment of stable claudication. DESIGN: Prospective,
      randomised trial. MATERIALS: Fifty-six patients with unilateral, stable, lower
      limb claudication assessed prior to randomisation, at 3 monthly intervals for 15
      months, and at approximately 6 years follow-up. Thirty-seven patients were
      available for long term review. OUTCOME MEASURES: Ankle/brachial pressure index
      (ABPI), treadmill claudication and maximum walking distances, percentage fall in
      ankle systolic pressure after exercise. RESULTS: Significant increases were seen
      in ABPI in the patients treated with PTA at all assessment to 15 months. However
      in terms of improved walking performance, the most significant changes in
      claudication and maximum walking distance were seen in the exercise training
      group. At long term follow-up, there was no significant difference between the
      groups. Subgroup analysis by angiographic site of disease showed greater
      functional improvement in those patients with disease confined to the superficial
      femoral artery treated by exercise training. The overall prognosis for the whole
      group of patients was benign, with only two (4%) undergoing amputation.
      CONCLUSIONS: Exercise training confers a greater improvement in claudication and
      maximum walking distance than PTA, especially in patients with disease confined
      to the superficial femoral artery.

PMID- 21855021
TI  - Commentary. Exercise training versus angioplasty for stable claudication. Long
      and medium term results of a prospective, randomised trial.

PMID- 21855022
TI  - Reprinted article "Factors associated with early failure of arteriovenous
      fistulae for haemodialysis access".
AB  - The radiocephalic arteriovenous fistula remains the method of choice for
      haemodialysis access. In order to assess their suitability for fistula formation,
      the radial arteries and cephalic veins were examined preoperatively by ultrasound
      colour flow scanner in conjunction with a pulse-generated run-off system.
      Intraoperative blood flow was measured after construction of the fistulae. Post
      operative follow-up was performed at various intervals to monitor the development
      of the fistulae. Radial artery and cephalic vein diameter less than 1.6 mm was
      associated with early fistula failure. The intraoperative fistula blood flow did
      not correlate with the outcome of the operation probably due to vessel spasm from
      manipulation. However, blood flow velocities measured non-invasively 1 day after
      the operation were significantly lower in fistulae that failed early compared
      with those that were adequate for haemodialysis. Most of the increase in fistula
      diameter and blood flow occur within the first 2 weeks of surgery.

PMID- 21855023
TI  - Commentary. Factors associated with early failure of arteriovenous fistulae for
      haemodialysis access.

PMID- 21855024
TI  - Reprinted article "Neovascularisation is the principal cause of varicose vein
      recurrence: results of a randomised trial of stripping the long saphenous vein".
AB  - OBJECTIVES: To determine whether routine stripping of the long saphenous vein
      reduces recurrence after varicose vein surgery. DESIGN: Randomised controlled
      trial. All operations done by a consultant vascular surgeon. Two year follow-up.
      MATERIALS AND METHODS: One hundred patients with primary long saphenous varicose
      veins (133 legs) were randomised. Two year follow-up in 81 patients (113 legs)
      with questionnaire, clinical examination and Duplex scanning. RESULTS: Some 89%
      remained satisfied with the results of their surgery, though 35% had recurrent
      veins on clinical examination. Recurrence was reduced from 43 to 25% in patients
      who had their long saphenous vein stripped (p = 0.04, chi(2)). Neovascularisation
      (serpentine tributaries arising from the ligated saphenofemoral junction) was
      detected in 52% of limbs and was the commonest cause of recurrence. Most
      tributaries were less than 3 mm in diameter and only caused recurrence if the
      long saphenous vein or a major thigh vein was intact. Twelve patients had
      tributaries greater than 3 mm diameter and all had recurrent varicose veins.
      CONCLUSIONS: Recurrence is common after varicose vein surgery and in this study
      was caused principally by neovascularisation at the ligated saphenofemoral
      junction. Clinical recurrence is reduced by routine stripping of the long
      saphenous vein.

PMID- 21855025
TI  - Commentary. Neovascularisation is the principal cause of varicose vein
      recurrence: results of a randomised trial of stripping the long saphenous vein.

PMID- 21855026
TI  - Reprinted article "Realistic expectations for patients with stent-graft treatment
      of abdominal aortic aneurysms. Results of a European multicentre registry".
AB  - OBJECTIVE: The outcomes for patients after endovascular treatment of abdominal
      aortic aneurysm (AAA) are determined primarily by the endpoints of death and
      endoleaks, the latter representing continued risk of rupture. The data of a
      multicentre registry were analysed with regard to the early outcome of stent
      graft procedures for AAA and the complications associated with this treatment. In
      addition, the results during follow-up were analysed by determining mortality and
      endoleak development as separate endpoints and as a combined endpoint defined as
      endoleak-free survival. SETTING: 38 European institutions of Vascular Surgery
      collaborating in a multicentre registry project. PATIENTS AND METHODS: 899
      patients with AAA underwent between May 1994 and March 1998 elective endovascular
      repair (818 men and 81 women; mean age 69 years). 80 (8.9%) of the patients had
      medical conditions that excluded them from open repair. 818 (91%) of patients had
      a bifurcated device, 63 (7%) had a straight tube graft, and only 18 (2%) had an
      aorto-uni-iliac device. Clinical examination and contrast-enhanced computed
      tomography was performed at fixed follow-up intervals to assess increase or
      decrease of the maximum transverse diameter (MTD). Endoleaks observed at follow
      up were discriminated into persistent endoleak and temporary endoleak. The latter
      is defined as single time observed endoleaks or with two or more negative imaging
      studies between observed endoleaks. Life-table analyses were used to calculate
      the rates of freedom-from-endoleak (no endoleak at any time), freedom-from
      persistent endoleak (no persistent endoleak), patient survival, and persistent
      endoleak-free-survival. RESULTS: The median follow-up of this patient series was
      6.2 months. The ratio between observed and expected follow-up data was 82% for
      the overall follow-up period. However, at 18 months of follow-up this rate was
      only 45%. The number of patients followed during this period was sufficient to
      allow statistically meaningful assessment. The MTD in patients with temporary
      endoleaks demonstrated a significant decrease at 6 to 12 months compared to
      preoperative values (mean 57 and 53 respectively, p = 0.004). In patients with
      persistent endoleaks there was no change between the preoperative and 6-month MTD
      (mean 57 and 60 mm respectively). At 6 and 18 months freedom-from-endoleak was
      83% and 74% and freedom-from-persistent endoleak was 93% and 90%, respectively.
      The 18-month cumulative patient survival was 88% and the main outcome measure,
      the persistent endoleak-free-survival was 79%. CONCLUSIONS: The MTD decreases in
      patients with temporary endoleak, but not in patients with persistent endoleak.
      Therefore, the use of the rate of freedom-from-persistent endoleak, reflecting
      absence of persisting endoleaks to estimate the prognosis with regard to the AAA,
      is justified. Determining persistent endoleak-free survival appears a rational
      approach to provide a realistic outlook for patients with stent-grafted AAA. The
      observed 18-month endoleak-free survival reflects a satisfactory mid-term result.

PMID- 21855027
TI  - Commentary. The fate of the claudicant--a prospective study of 1969 claudicants.

PMID- 21855028
TI  - Commentary. Realistic expectations for patients with stent-graft treatment of
      abdominal aortic aneurysms. Results of a European multicentre registry.

PMID- 21855029
TI  - Reprinted article "Carotid artery disease and stroke during coronary artery
      bypass: a critical review of the literature".
AB  - OBJECTIVES: To determine the role of carotid artery disease in the
      pathophysiology of stroke after coronary artery bypass (CABG). DESIGN: Systematic
      review of the literature. RESULTS: The risk of stroke after CABG was 2% and
      remained unchanged between 1970-2000. Two-thirds occurred after day 1 and 23%
      died. 91% of screened CABG patients had no significant carotid disease and had a
      <2% risk of peri-operative stroke. Stroke risk increased to 3% in predominantly
      asymptomatic patients with a unilateral 50-99% stenosis, 5% in those with
      bilateral 50-99% stenoses and 7-11% in patients with carotid occlusion.
      Significant predictive factors for post-CABG stroke included; (i) carotid bruit
      (OR 3.6, 95% CI 2.8-4.6), (ii) prior stroke/TIA (OR 3.6, 95% CI 2.7-4.9) and
      (iii) severe carotid stenosis/occlusion (OR 4.3, 95% CI 3.2-5.7). However, the
      systematic review indicated that 50% of stroke sufferers did not have significant
      carotid disease and 60% of territorial infarctions on CT scan/autopsy could not
      be attributed to carotid disease alone. CONCLUSIONS: Carotid disease is an
      important aetiological factor in the pathophysiology of post-CABG stroke.
      However, even assuming that prophylactic carotid endarterectomy carried no
      additional risk, it could only ever prevent about 40-50% of procedural strokes.

PMID- 21855031
TI  - Reprinted article "Endovascular repair with bifurcated stent-grafts under local
      anaesthesia to improve outcome of ruptured aortoiliac aneurysms".
AB  - INTRODUCTION: Acute haemodynamic changes and/or loss of abdominal muscle tone can
      occur during induction of general anaesthesia and may be the Achilles' tendon in
      endovascular aneurysm repair (EVAR) of ruptured aortoiliac aneurysms (rAIA). The
      purpose of this study was to evaluate the use of local anaesthesia (LA) for EVAR
      to overcome these limitations. METHODS: Twenty-one consecutive patients with rAIA
      are included in this study. Twenty patients underwent EVAR under LA, and 1
      patient was treated under general anaesthesia. Haemodynamics were stabilised
      during assessment of EVAR feasibility by CT-scan and during the procedure itself
      by controlled hypotension (MAP 50-60 mmHg) and moderate fluid resuscitation.
      RESULTS: Median procedure time was 120 min. Haemodynamics remained stable in all
      but 3 patients who required transfemoral balloon occlusion of the supra-renal
      aorta. Perioperative intubation was necessary in 5 patients because of
      respiratory distress (n = 3), or retroperitoneal access (n = 2). Temporary
      deterioration of renal function occurred in 6 patients, with 2 requiring
      hemofiltration. CT-scan confirmed sealing of the rAIA in all patients at
      discharge. 30-day mortality was 9.5% (2 deaths). In the median follow-up of 19
      months, there were no deaths, but 3 endovascular re-interventions, 1 crossover
      femoro-femoral bypass, and 1 open surgical graft repair. DISCUSSION: Our series
      is the first to show that EVAR for rAIA can be safely performed under LA. This
      approach allows implantation of commercially available bifurcated SG and improves
      patient outcome.

PMID- 21855030
TI  - Commentary. Carotid artery disease and stroke during coronary artery bypass: a
      critical review of the literature.

PMID- 21855032
TI  - Reprinted article "Subintimal angioplasty of femoropopliteal artery occlusions:
      the long-term results".
AB  - The technique of subintimal angioplasty has been attempted on 200 consecutive
      femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The
      principle of the technique is to traverse the occlusion in the subintimal plane
      and recanalise by inflating the angioplasty balloon within the subintimal space.
      The technical success rate was 159/200 (80%) and was not significantly different
      for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n =
      23), p = 0.20. There were no deaths nor limb loss resulting from the procedure.
      The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0)
      preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic
      patencies of technically successful procedures at 12 and 36 months were 71% and
      58% respectively, the symptomatic patencies were 73% and 61%. A multiple
      regression analysis showed that smoking multiplied the risk of reocclusion by
      2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p <
      0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion
      length. In conclusion, the technical success rate (80%) of subintimal angioplasty
      for femoropopliteal occlusions is unrelated to occlusion length and for all
      procedures, including technical failures, cumulative symptomatic and haemodynamic
      patencies of 46 and 48% can be achieved at 3 years. The factors influencing long
      term patency were smoking, the number of calf run-off vessels and occlusion
      length.

PMID- 21855033
TI  - Commentary. Endovascular repair with bifurcated stent-grafts under local
      anaesthesia to improve outcome of ruptured aortoiliac aneurysms.

PMID- 21855034
TI  - Reprinted article "A combination of statins and beta-blockers is independently
      associated with a reduction in the incidence of perioperative mortality and
      nonfatal myocardial infarction in patients undergoing abdominal aortic aneurysm
      surgery".
AB  - OBJECTIVE: To investigate the combined beneficial effect of statin and beta
      blocker use on perioperative mortality and myocardial infarction (MI) in patients
      undergoing abdominal aortic aneurysm surgery (AAA). BACKGROUND: Patients
      undergoing elective AAA-surgery identified by clinical risk factors and
      dobutamine stress echocardiography (DSE) as being at high-risk often have
      considerable cardiac complication rate despite the use of beta-blockers. METHODS:
      We studied 570 patients (mean age 69 +/-9 years, 486 males) who underwent AAA
      surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for
      clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus,
      stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta
      blocker use. The main outcome was a composite of perioperative mortality and MI
      within 30 days of surgery. RESULTS: Perioperative mortality or MI occurred in 51
      (8.9%) patients. The incidence of the composite endpoint was significantly lower
      in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR):
      0.31, 95% confidence interval (CI): 0.13-0.74; p = 0.01). After correcting for
      other covariates, the association between statin use and reduced incidence of the
      composite endpoint remained unchanged (OR: 0.24,95% CI: 0.10-0.70; p = 0.01).
      Beta-blocker use was also associated with a significant reduction in the
      composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of
      statins and beta-blockers appeared to be at lower risk for the composite endpoint
      across multiple cardiac risk strata; particularly patients with 3 or more risk
      factors experienced significantly lower perioperative events. CONCLUSIONS: A
      combination of statin and beta-blocker use in patients with AAA-surgery is
      associated with a reduced incidence of perioperative mortality and nonfatal MI
      particularly in patients at the highest risk.

PMID- 21855035
TI  - An algorithm for the management of hypertension in the setting of vascular
      endothelial growth factor signaling inhibition.
AB  - Vascular endothelial growth factor (VEGF) signaling is considered to be one of
      the key factors involved in tumor-associated angiogenesis. Inhibition of
      angiogenesis has significantly improved anticancer therapy making it one of the
      cornerstones of treatment for various solid tumors. Several antiangiogenesis
      inhibitory compounds (eg, bevacizumab, sunitinib, sorafenib) are now widely used
      in the treatment of patients with colorectal, non-small-cell lung, advanced renal
      cell, hepatocellular, and breast cancer. One of the most commonly observed side
      effects of inhibition of VEGF signaling is hypertension, which is dose-dependent
      and varies in incidence among the different angiogenesis inhibitor drugs. Poorly
      controlled hypertension not only can lead to cardiovascular events, renal
      disease, and stroke, but may also necessitate discontinuation of anticancer
      therapy, thereby potentially limiting overall clinical benefit. In contrast,
      hypertension induced by VEGF inhibitors has been shown to represent an important
      pharmacodynamic biomarker of oncologic response. For the practicing oncologist,
      knowledge and optimal management of this toxicity is essential. Because of the
      lack of controlled studies on this topic, no clear recommendations are available.
      In this article, we review the available preclinical and clinical data on the
      pathogenesis and management of hypertension resulting from anti-VEGF inhibitor
      therapy and propose a treatment algorithm that our group has now implemented for
      daily clinical practice.

PMID- 21855036
TI  - A review of excision repair cross-complementation group 1 in colorectal cancer.
AB  - Oxaliplatin-based chemotherapy is the standard of care in patients with high-risk
      stage II and stage III colorectal cancer as well as in patients with advanced
      disease. Unfortunately, a large proportion of patients offered oxaliplatin fail
      to benefit from it. In the era of personalized treatment, there are strong
      efforts to identify biomarkers that will predict efficacy to oxaliplatin-based
      treatments. Excision repair cross-complementation group 1 (ERCC1) is a key
      element in the nucleotide excision repair (NER) pathway, which is responsible for
      repairing DNA adducts induced by platinum compounds. ERCC1 has recently been
      shown to be closely associated with outcome in patients with non-small-cell lung
      cancer (NSCLC): both high ERCC1 protein and gene expression are associated with
      resistance to cisplatin-based chemotherapy and better outcome without treatment.
      Therefore, ERCC1 has the potential to be used as a strong candidate biomarker,
      both predictive and prognostic, for colorectal cancer. This review will focus on
      the preclinical and clinical evidences supporting ERCC1 as a major molecule in
      oxaliplatin resistance. In addition, the important technologies used to assess
      ERCC1 gene and protein expression will be highlighted.

PMID- 21855037
TI  - Nonsurgical management of esophageal adenocarcinoma.
AB  - BACKGROUND: The benefit of induction chemotherapy (IC) before chemoradiotherapy
      (CRT) for inoperable esophageal adenocarcinoma has not been established. To
      clarify toxicities and outcomes of combined modality treatment, we performed a
      retrospective review. MATERIALS AND METHODS: Sixty-eight consecutive patients
      were identified. Fifty-one patients had CRT, 17 had radiotherapy (RT). Fifty
      eight received IC before RT. IC consisted of 4 cycles of platinum and
      fluoropyrimidines followed by CRT 54 Gy with concurrent infusional 5-fluorouracil
      (5-FU) or capecitabine. Response to IC was assessed at 3 months and response to
      CRT at 3 months. Time to progression (TTP) and overall survival (OS) are
      reported. RESULTS: Fifty-four patients were men and 14 were women, with median
      age 72 years (range, 42-87 years). There were 29 stage II, 33 stage III, 4 stage
      IVa, and 2 stage IVb tumors. The response 3 months after completion of treatment
      was 39.6%. No grade 4 toxicity was reported, but 10/58 patients had grade 3
      toxicity from IC. The median TTP and OS from RT for the entire cohort was 12
      months (95% confidence interval [CI], 7-18) and 16 months (95% CI, 5-27),
      respectively. The 1- and 2-year survival rates from diagnosis were 73% and 47%,
      respectively. There was no statistically significant difference in TTP or OS in
      patients who responded to IC compared with those who did not (median TTP 11 vs.
      12 months, respectively; P = .8; median OS 15 vs. 14 months, respectively; P =
      .8). CONCLUSION: The outcome in patients with adenocarcinoma of the esophagus
      after CRT is comparable to unselected surgical series. Response to IC is not
      always an indicator of eventual outcome.

PMID- 21855039
TI  - Durable complete responses in metastatic colorectal cancer treated with
      chemotherapy alone.
AB  - BACKGROUND/PURPOSE: The median survival for patients with metastatic colorectal
      cancer (mCRC) has progressively increased over the past decades. Since the
      introduction of 5-fluorouracil (5-FU)-based chemotherapy, followed by hepatic
      resection of metastases, and more recently the adoption of newer chemotherapeutic
      regimens associated with targeted therapy, the gains are getting more
      substantial. Despite the recognition of the potential for long-term survival
      after surgical resection of metastatic disease, long-term survival data to
      determine the potential curative role of chemotherapy alone is lacking. METHODS:
      We performed a retrospective review of 2751 patients who presented with mCRC at
      The MD Anderson Cancer Center from 1990 through 2003. Patients alive at 5 years
      who achieved complete response with chemotherapy and were not submitted to any
      surgical or interventional procedures directed to the metastatic sites were
      included in the analysis. RESULTS: The 5-year overall survival rate for all
      patients with mCRC during this period was 10.8%. Among these long-term survivors,
      2.2% achieved a sustained complete response after chemotherapy (all 6 with
      fluoropyrimidines and 2 with irinotecan) as the only treatment modality and were
      without evidence of disease until the last follow-up visit (median of 10.3
      years). This number corresponds to 0.24% (6 of 2541) of all patients with mCRC
      included in this review. CONCLUSION: Cure with chemotherapy alone is possible for
      a very small number of patients with metastatic colorectal cancer. Improved
      therapies are increasing complete response rates, but the impact of modern
      chemotherapy on durable complete responses will require additional follow up.

PMID- 21855038
TI  - An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second
      line therapy in patients with metastatic colorectal cancer.
AB  - BACKGROUND: This prospective analysis evaluated the effect of tumor KRAS status
      on efficacy of second-line panitumumab plus folinic acid/5
      fluorouracil/irinotecan (FOLFIRI). METHODS: This phase 2, open-label, single-arm
      study enrolled patients with unresectable, measurable metastatic colorectal
      cancer (mCRC) after failure of first-line treatment with oxaliplatin-based
      chemotherapy plus bevacizumab. Patients received panitumumab 6 mg/kg plus FOLFIRI
      every 2 weeks until disease progression or intolerability. Tumor assessments per
      Response Evaluation Criteria in Solid Tumors (RECIST) were performed by the
      investigators every 8 weeks from weeks 8-32 and every 12 weeks thereafter. KRAS
      status was determined by real-time polymerase chain reaction (PCR) on DNA
      extracted from fixed tumor sections. Efficacy endpoints included objective
      response rate, progression-free survival (PFS), and overall survival (OS). Safety
      endpoints included incidence of adverse events (AEs). Endpoints were evaluated by
      tumor KRAS status. RESULTS: Of 116 patients enrolled, 109 patients with known
      tumor KRAS status received treatment; 59% had wild-type KRAS, and 41% had mutant
      KRAS. Fifteen patients (23%) with wild-type KRAS and 7 patients (16%) with mutant
      KRAS had a complete or partial response to treatment. Median PFS was 26 weeks
      (95% CI, 19-33 weeks) and 19 weeks (95% CI, 12-25 weeks) in the wild-type KRAS
      and mutant KRAS strata, respectively. Median OS was 50 weeks (95% CI, 39-76
      weeks) and 31 weeks (95% CI, 23-47 weeks) in wild-type KRAS and mutant KRAS
      strata, respectively. Skin-related toxicities (86% of all patients) and diarrhea
      (74%) were the most common AEs. CONCLUSION: Panitumumab plus FOLFIRI numerically
      improved objective response rate, PFS, and OS in favor of patients with wild-type
      KRAS tumors. The safety profile was consistent with panitumumab plus FOLFIRI
      trials in similar patient populations.

PMID- 21855040
TI  - Laparoscopic radical correction combined with extensive lymphadenectomy and
      pelvic autonomic nerve preservation for mid-to-low rectal cancer.
AB  - OBJECTIVE: The purposes of this study were to confirm the definite metastasis and
      micrometastasis rate of upward and lateral lymph nodes of mid-to-low rectal
      cancer at stage II and stage III, and to evaluate the feasibility and safety of
      laparoscopic radical correction combined with extensive lymphadenectomy and
      pelvic autonomic nerve preservation (PANP). METHODS: The study was performed in
      68 patients who were diagnosed with mid-to-low rectal cancer at stage II or stage
      III and received laparoscopic radical correction combined with extensive
      lymphadenectomy and PANP from June 2006 to June 2008 in the General Surgery
      Department of Southwest Hospital. All lymph nodes resected in the surgeries were
      examined by hematoxylin and eosin (H & E) stain and immunohistochemistry with an
      antibody against cytokeratin 20 (CK20) to confirm the conditions of metastasis
      and micrometastasis. We compared the postoperative complications with those of
      traditional surgeries. RESULTS: In 1571 lymph nodes, 16 lymph nodes were found to
      have definite metastasis in 6 patients (8.8%) and in 41 lymph nodes we found
      micrometastasis in 12 patients (17.6%). The total metastasis rate of upward and
      lateral lymph nodes was 19.1%. Compared with traditional surgeries, the new
      surgery had less blood loss and short convalescence and postoperative
      complications were not increased. CONCLUSION: The total metastasis rate of upward
      and lateral lymph nodes is 19.1%. The laparoscopic radical correction combined
      with extensive lymphadenectomy and PANP is feasible and safe.

PMID- 21855042
TI  - Lactic acidosis and colon cancer: oncologic emergency?
AB  - We report the case of a 44-year-old woman who presented shortly after the
      diagnosis of metastatic colon cancer with profound lactic acidosis in the absence
      of tissue hypoperfusion or hypoxemia. Her acid-base disturbance was unresponsive
      to medical management but resolved after initiation of systemic chemotherapy. In
      addition to malignancy associated lactic acidosis, this case illustrates several
      other issues, including factors involved in choosing the initial chemotherapy
      regimen and sequencing subsequent therapies, and the role of carcinoembryonic
      antigen (CEA) in following response to treatment. It is important to report this
      case of a rare but serious complication of malignancy in order to increase
      recognition and understanding of this presentation.

PMID- 21855041
TI  - Expression of the antiapoptotic protein survivin in colon cancer.
AB  - BACKGROUND: The antiapoptotic protein survivin has been demonstrated to play an
      important role in colorectal carcinogenesis. However it is unclear whether the
      upregulation of survivin is maintained through progressive stages of disease, or
      if other apoptosis-related genes are coexpressed and/or repressed. We sought to
      evaluate survivin expression in colonic neoplasia and identify relationships with
      additional regulators of apoptosis. PATIENTS AND METHODS: Tissue samples from 168
      patients with primary colorectal cancer were profiled using the GeneChip Human
      Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) and evaluated for
      survivin expression. Immunohistochemical staining for survivin and a panel of
      apoptosis-associated proteins were used in 86 patients with tissue microarray
      (TMA) blocks; scoring was by stain intensity and percentage of positive cells
      (range, 0-9). RESULTS: Survivin mRNA was upregulated (1.8-fold increase) in
      primary colon cancers- irrespective of American Joint Committee on Cancer (AJCC)
      stage- and metastases compared with normal colonic tissue (P < .0001). Survivin
      staining was positive in 93% of adenocarcinomas (median immunohistochemistry
      [IHC] score: 2 [range, 1-6]), 100% of adenomas (1 [range,1-2]), and 43% of normal
      colonic mucosa (1, [range 1-2]) (P = .006). Survivin expression increased with
      worsening tumor grade (P < .05). In colon cancers, survivin expression positively
      correlated with the coexpression of PUMA (P < .001), TACE (P = .003), and MCL1 (P
      = .01), and trended toward an inverse correlation with BAX (P = .058).
      CONCLUSIONS: Survivin expression increases during the normal mucosa-adenoma
      carcinoma sequence and is maintained throughout progression of disease, which
      strengthens its appeal as a therapeutic target. Furthermore, we have demonstrated
      co-overexpression of several other apoptosis-related genes, which may in turn
      serve as additional and potentially synergistic therapeutic targets.

PMID- 21855043
TI  - Fatal diffuse alveolar damage associated with oxaliplatin administration.
AB  - Oxaliplatin-based chemotherapy regimens are currently a standard of care for the
      treatment of colorectal cancer in both the adjuvant and metastatic disease
      settings. Significant improvements in survival have resulted from the use of
      oxaliplatin-based combinations. This article describes the use of oxaliplatin
      based chemotherapy in a patient with stage III colon cancer who developed fatal
      diffuse alveolar damage during his adjuvant therapy. Other cases of pulmonary
      toxicity associated with oxaliplatin use are presented and the proposed
      pathophysiology of this rare occurrence is discussed.

PMID- 21855045
TI  - Revised TNM staging for colorectal cancer: did we miss the golden opportunity to
      do right by the staging?

PMID- 21855044
TI  - Body surface area-based dosing of 5-fluoruracil results in extensive
      interindividual variability in 5-fluorouracil exposure in colorectal cancer
      patients on FOLFOX regimens.

PMID- 21855047
TI  - Perspectives--August 2010.

PMID- 21855046
TI  - A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose
      bevacizumab in the treatment of metastatic colorectal cancer.
AB  - BACKGROUND: This study was designed to determine the efficacy and tolerability of
      a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in
      patients with chemo-naive advanced colorectal cancer. PATIENTS AND METHODS:
      Nineteen patients with previously untreated advanced colorectal cancer received
      capecitabine at 1000 mg/m(2) twice a day on days 1-5 and days 8-12 of a 14-day
      cycle, and OHP at 85 mg/m(2) and bevacizumab at 10 mg/kg every 2 weeks. Because
      of unacceptable toxicities, the capecitabine dose was reduced to 850 mg/m(2).
      Thirty-one additional patients were treated at the lower capecitabine dose.
      Treatment continued until disease progression, persistent intolerable toxicity,
      or physician and/or patient discretion. RESULTS: Overall, toxicities were better
      managed and tolerated at the 850 mg/-m(2) capecitabine dose. The most common
      treatment-related grade >= 3 toxicities were diarrhea and sensory neuropathy. In
      the first 19 subjects, the response rate was 63% (95% confidence interval [CI],
      38%-84%) and 5 patients had stable disease; median progression-free survival
      (PFS) was 10.1 months (95% CI, 5.7-19.5 months). In the subsequent 31 patients,
      the response was 42% (95% CI, 25%-61%); 11 patients had stable disease and median
      PFS was 10.4 months (95% CI, 6.9-15.4); median overall survival was 24.8 months
      (95% CI, 12.9-39.7). CONCLUSIONS: This novel regimen of capecitabine at 850
      mg/m(2) twice a day on days 1-5 and days 8-12 and OHP at 85 mg/m(2)and
      bevacizumab at 10 mg/kg every 14 days is clinically active in advanced colorectal
      cancer. The toxicity profile of this regimen is consistent with the standard
      every-3-week dosing schedule.

PMID- 21855049
TI  - On letter frequency effects.
AB  - In four experiments we examined whether the frequency of occurrence of letters
      affects performance in the alphabetic decision task (speeded letter vs. pseudo
      letter classification). Experiments 1A and 1B tested isolated letters and pseudo
      letters presented at fixation, and Experiments 2A and 2B tested the same stimuli
      inserted at the 1st, 3rd, or 5th position in a string of Xs. Significant negative
      correlations between letter frequency and response times to letter targets were
      found in all experiments. The correlations were found to be stronger for token
      frequency counts compared with both type frequency and frequency rank, stronger
      for frequency counts based on a book corpus compared with film subtitles, and
      stronger for measures counting occurrences as the first letter of words compared
      with inner letters and final letters. Correlations for letters presented in
      strings of Xs were found to depend on letter case and position-in-string. The
      results are in favor of models of word recognition that implement case-specific
      and position-specific letter representations.

PMID- 21855048
TI  - [Closure of recurrent cleft palate fistulas with plasma rich in growth factors].
AB  - INTRODUCTION AND OBJECTIVE: Fistulas represent a significant challenge in the
      treatment of cleft palate. The best outcome of a palatoplasty is obtained with a
      competent velopharyngeal sphincter and a palate without fistulas. The recurrence
      of primary cleft palate fistula is reported as high as up to 76%, and to nearly
      100% in recurrent fistulas. Plasma rich in growth factors (PRGF) is an autologous
      blood product with biologically active substances that enhance tissue repair
      mechanisms such as chemotaxis, cell proliferation, angiogenesis, osteogenesis and
      remodeling. Its use in cleft palate fistulas has not been reported. Our objective
      was to evaluate closure of recurrent cleft palate fistulas using PRGF mixed with
      autologous bone graft. METHODS: An experimental, prospective, longitudinal study
      was carried out from April 2008 to July 2010 on 11 recurrent cleft palate
      fistulas that were closed with local mucoperiosteal flaps and placement of
      autologous bone graft mixed with PRGF. RESULTS: Complete closure of palate
      fistulas was achieved in 90.9% (follow-up of 6-24 months), decreasing the
      reported incidence for the recurrence by other authors with other techniques.
      CONCLUSIONS: The use of PRGF mixed with autologous bone graft seems to be an
      effective, safe and low-cost technique for the closure of recurrent cleft palate
      fistulas. However, we consider its study must be extended.

PMID- 21855050
TI  - Scholarship during residency training: a controlled comparison study.

PMID- 21855051
TI  - Longitudinal study of macular folds by spectral-domain optical coherence
      tomography.
AB  - PURPOSE: To understand the natural history of macular folds using serial spectral
      domain optical coherence tomography (SD-OCT). DESIGN: Prospective case series.
      METHOD: Serial OCTs were performed using Topcon 3D OCT. The main outcome measures
      were: patient demographics; preoperative, perioperative, and postoperative
      details; serial SD-OCTs; and length of follow-up. RESULTS: Ten patients who
      underwent standard 3-port pars plana vitrectomy with gas tamponade to repair
      rhegmatogenous retinal detachment were included in this study. Mean follow-up was
      9.9 months (range 5-17 months). Three types of retinal folds were identified: 1)
      ripple; 2) taco; 3) displacement. Ripple and taco folds were found to resolve
      spontaneously. Outer retinal hyperreflective lesions resolved first, followed by
      flattening of the inner retinal layers. Displacement folds also resolved, but
      left the macula translocated inferiorly, causing binocular diplopia. CONCLUSION:
      Ripple and taco folds could be managed conservatively with good outcomes.
      However, the optimal treatment of displacement folds requires further research.

PMID- 21855052
TI  - Variation of telomeric DNA content in gingiva and dental pulp.
AB  - OBJECTIVE: The purpose of the present study was to examine the age- and tissue
      related variations of the telomere length in gingiva and dental pulp of donor
      patients. DESIGN: We quantified the relative telomeric DNA content corresponding
      to the telomere length in gingiva or dental pulp from donor patients (male and
      female, aged at 19-68) by using genomic DNA of oral tissues in dot-blot
      hybridization with telomere-specific probe. RESULTS: Telomeric DNA content in the
      dental pulp showed a negative correlation with the age of donor patients, with
      smaller telomeric DNA content observed in the elders (p<0.05). In age-matched
      gingival samples, the average telomeric DNA content was not significantly
      different between male and female donors. In the age- and gender-matched samples,
      telomeric DNA content was significantly greater (p<0.001) in dental pulp than in
      gingiva. CONCLUSION: The telomere length is greater in the dental pulp than in
      the gingiva. In the dental pulp, but not in the gingiva, telomere length shortens
      with age.

PMID- 21855053
TI  - De novo rates and selection of schizophrenia-associated copy number variants.
AB  - BACKGROUND: At least 10 large and rare recurrent DNA copy number variants (CNVs)
      have been identified as risk factors for schizophrenia and other
      neurodevelopmental disorders. Because such conditions are associated with reduced
      fecundity, these pathogenic CNVs should be filtered out from the population by
      selection and must be replenished by de novo events. METHODS: To estimate the
      mutation rate (MU) for these CNVs and the selection pressure (s) against them, we
      first conducted a literature review on the rate of each of these CNVs in the
      population and the rate of their de novo occurrence. In each generation, the
      number of CNVs lost because of reduced fertility must be replenished by the same
      number of de novo CNVs. Therefore, the observed ratio of de novo versus all
      (inherited + de novo) CNVs approximates the selection coefficient (s) of that
      CNV. The mutation rate approximates to MU = s * q, where q is the frequency of
      the CNV in the population. RESULTS: High selection pressure operates at all these
      loci (s = .12 - .88), suggesting that following de novo occurrence, each of these
      CNVs persists in the population in only a few generations. The mutation rate for
      each CNV is high, affecting between 1:3500 and 1:30,000 individuals. The rarest
      CNVs have the highest selection coefficients. CONCLUSIONS: The CNVs that increase
      risk to develop schizophrenia are caused by recent de novo mutations and are
      under strong selection pressure. They persist in the population because of high
      mutation rates.

PMID- 21855056
TI  - Interferon beta-1b directly modulates human neural stem/progenitor cell fate.
AB  - Interferon beta (IFN-beta) is a mainline treatment for multiple sclerosis (MS);
      however its exact mechanism of action is not completely understood. IFN-beta is
      known as an immunomodulator; although recent evidence suggests that IFN-beta may
      also act directly on neural stem/progenitor cells (NPCs) in the central nervous
      system (CNS). NPCs can differentiate into all neural lineage cells, which could
      contribute to the remyelination and repair of MS lesions. Understanding how IFN
      beta influences NPC physiology is critical to develop more specific therapies
      that can better assist this repair process. In this study, we investigated the
      effects of IFN beta-1b (Betaseron(r)) on human NPCs in vitro (hNPCs). Our data
      demonstrate a dose-dependent response of hNPCs to IFN beta-1b treatment via
      sustained proliferation and differentiation. Furthermore, we offer insight into
      the signaling pathways involved in these mechanisms. Overall, this study shows a
      direct effect of IFN beta-1b on hNPCs and highlights the need to further
      understand how current MS treatments can modulate endogenous NPC populations
      within the CNS.

PMID- 21855055
TI  - Glutamatergic plasticity in medial prefrontal cortex and ventral tegmental area
      following extended-access cocaine self-administration.
AB  - Glutamate signaling in prefrontal cortex and ventral tegmental area plays an
      important role in the molecular and behavioral plasticity associated with
      addiction to drugs of abuse. The current study investigated the expression and
      postsynaptic density redistribution of glutamate receptors and synaptic
      scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and
      ventral tegmental area after cocaine self-administration. After 14 days of
      extended-access (6h/day) cocaine self-administration, rats were exposed to one of
      three withdrawal regimen for 10 days. Animals either stayed in home cages (Home),
      returned to self-administration boxes with the levers withdrawn (Box), or
      underwent extinction training (Extinction). Extinction training was associated
      with significant glutamatergic plasticity. In dorsomedial prefrontal cortex of
      the Extinction group, there was an increase in postsynaptic density GluR1, PSD95,
      and actin proteins; while postsynaptic density mGluR5 protein decreased and there
      was no change in NMDAR1, Homer1b/c, or PICK1 proteins. These changes were not
      observed in ventromedial prefrontal cortex or ventral tegmental area. In ventral
      tegmental area, Extinction training reversed the decreased postsynaptic density
      NMDAR1 protein in the Home and Box withdrawal groups. These data suggest that
      extinction of drug seeking is associated with selective glutamatergic plasticity
      in prefrontal cortex and ventral tegmental area that include modulation of
      receptor trafficking to postsynaptic density.

PMID- 21855054
TI  - Intravenous ethanol infusion decreases human cortical gamma-aminobutyric acid and
      N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4
      tesla.
AB  - BACKGROUND: Ethanol modulates glutamate and gamma-aminobutyric (GABA) function.
      However, little is known about the acute pharmacologic effects of ethanol on
      levels of GABA, glutamate, and other metabolites measurable in the human cortex
      in vivo with proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Eleven
      healthy social drinkers received two intravenous ethanol infusions that raised
      breath alcohol levels to a clamped plateau of 60 mg/dL over 60-70 min. The first
      infusion established tolerability of the procedure, and the second procedure,
      conducted 15 +/- 12 days later, was performed during (1)H-MRS of occipital GABA,
      glutamate, and other metabolites. RESULTS: The time course of brain ethanol
      approximated that of breath ethanol, but venous ethanol lagged by approximately 7
      min. The GABA fell 13 +/- 8% after 5 min of the ethanol infusion and remained
      reduced (p = .003) throughout the measurement. The combination of N
      acetylaspartate and N-acetylaspartyl glutamate (summed as NAA) fell steadily
      during the infusion by 8 +/- 3% (p = .0036). CONCLUSIONS: Ethanol reduced
      cortical GABA and NAA levels in humans. Reductions in GABA levels are consistent
      with facilitation of GABA(A) receptor function by ethanol. The gradual decline in
      NAA levels suggests inhibition of neural or metabolic activity in the brain.

PMID- 21855058
TI  - Numerical ordering ability mediates the relation between number-sense and
      arithmetic competence.
AB  - What predicts human mathematical competence? While detailed models of number
      representation in the brain have been developed, it remains to be seen exactly
      how basic number representations link to higher math abilities. We propose that
      representation of ordinal associations between numerical symbols is one important
      factor that underpins this link. We show that individual variability in symbolic
      number-ordering ability strongly predicts performance on complex mental
      arithmetic tasks even when controlling for several competing factors, including
      approximate number acuity. Crucially, symbolic number-ordering ability fully
      mediates the previously reported relation between approximate number acuity and
      more complex mathematical skills, suggesting that symbolic number-ordering may be
      a stepping stone from approximate number representation to mathematical
      competence. These results are important for understanding how evolution has
      interacted with culture to generate complex representations of abstract numerical
      relationships. Moreover, the finding that symbolic number-ordering ability links
      approximate number acuity and complex math skills carries implications for
      designing math-education curricula and identifying reliable markers of math
      performance during schooling.

PMID- 21855057
TI  - Synthetic adjuvants for vaccine formulations: evaluation of new phytol
      derivatives in induction and persistence of specific immune response.
AB  - Terpenoids are ubiquitous natural compounds that have been shown to improve
      vaccine efficacy as adjuvants. To gain an understanding of the structural
      features important for adjuvanticity, we studied compounds derived from a
      diterpene phytol and assessed their efficacy. In a previous report, we showed
      that phytol and one of its derivatives, PHIS-01 (a phytol-derived
      immunostimulant, phytanol), are excellent adjuvants. To determine the effects of
      varying the polar terminus of PHIS-01, we designed amine and mannose-terminated
      phytol derivatives (PHIS-02 and PHIS-03, respectively). We studied their relative
      efficacy as emulsions with soluble proteins, ovalbumin, and a hapten-protein
      conjugate phthalate-KLH. Immunological parameters evaluated consisted of specific
      antibody responses in terms of titers, specificities and isotype profiles, T cell
      involvement and cytokine production. Our results indicate that these new
      isoprenoids were safe adjuvants with the ability to significantly augment
      immunogen-specific IgG1 and IgG2a antibody responses. Moreover, there was no
      adverse phthalate cross-reactive anti-DNA response. Interestingly, PHIS-01 and
      PHIS-03 influenced differentially T-helper polarization. We also observed that
      these compounds modulated the immune response through apoptotic/necrotic effects
      on target tumor cells using murine lymphomas. Finally, unlike squalene and
      several other terpenoids reported to date, these phytol derivatives did not
      appear arthritogenic in murine models.

PMID- 21855059
TI  - Traffic density and stationary sources of air pollution associated with wheeze,
      asthma, and immunoglobulin E from birth to age 5 years among New York City
      children.
AB  - Exposures to ambient air traffic-related pollutants and their sources have been
      associated with respiratory and asthma morbidity in children. However,
      longitudinal investigation of the effects of traffic-related exposures during
      early childhood is limited. We examined associations of residential proximity and
      density of traffic and stationary sources of air pollution with wheeze, asthma,
      and immunoglobulin (Ig) E among New York City children between birth and age 5
      years. Subjects included 593 Dominican and African American participants from the
      Columbia Center for Children's Environmental Health cohort. Prenatally, through
      age 5 years, residential and respiratory health data were collected every 3-6
      months. At ages 2, 3, and 5 years, serum IgE was measured. Spatial data on the
      proximity and density of roadways and built environment were collected for a 250
      m buffer around subjects' homes. Associations of wheeze, asthma, total IgE, and
      allergen-specific IgE with prenatal, earlier childhood, and concurrent exposures
      to air pollution sources were analyzed using generalized estimating equations or
      logistic regression. In repeated measures analyses, concurrent residential
      density of four-way intersections was associated significantly with wheeze (odds
      ratio: 1.26; 95% confidence interval [CI]: 1.01, 1.57). Age 1 exposures also were
      associated with wheeze at subsequent ages. Concurrent proximity to highway was
      associated more strongly with total IgE (ratio of the geometric mean levels:
      1.25; 95% CI: 1.09, 1.42) than were prenatal or earlier childhood exposures.
      Positive associations also were observed between percent commercial building area
      and asthma, wheeze, and IgE and between proximity to stationary sources of air
      pollution and asthma. Longitudinal investigation suggests that among Dominican
      and African American children living in Northern Manhattan and South Bronx during
      ages 0-5 years, residence in neighborhoods with high density of traffic and
      industrial facilities may contribute to chronic respiratory morbidity, and
      concurrent, prenatal, and earlier childhood exposures may be important. These
      findings may have broad implications for other urban populations that commonly
      have high asthma prevalence and exposure to a high density of traffic and
      stationary air pollution sources.

PMID- 21855060
TI  - Tracy-Widom distribution based fault detection approach: application to aircraft
      sensor/actuator fault detection.
AB  - The fault detection approach based on the Tracy-Widom distribution is presented
      and applied to the aircraft flight control system. An operative method of testing
      the innovation covariance of the Kalman filter is proposed. The maximal
      eigenvalue of the random Wishart matrix is used as the monitoring statistic, and
      the testing problem is reduced to determine the asymptotics for the largest
      eigenvalue of the Wishart matrix. As a result, an algorithm for testing the
      innovation covariance based on the Tracy-Widom distribution is proposed. In the
      simulations, the longitudinal and lateral dynamics of the F-16 aircraft model is
      considered, and detection of sensor and control surface faults in the flight
      control system which affect the innovation covariance, are examined.

PMID- 21855061
TI  - Robust design of a 2-DOF GMV controller: a direct self-tuning and fuzzy
      scheduling approach.
AB  - This paper presents a study on self-tuning control strategies with generalized
      minimum variance control in a fixed two degree of freedom structure-or simply
      GMV2DOF-within two adaptive perspectives. One, from the process model point of
      view, using a recursive least squares estimator algorithm for direct self-tuning
      design, and another, using a Mamdani fuzzy GMV2DOF parameters scheduling
      technique based on analytical and physical interpretations from robustness
      analysis of the system. Both strategies are assessed by simulation and real
      plants experimentation environments composed of a damped pendulum and an under
      development wind tunnel from the Department of Automation and Systems of the
      Federal University of Santa Catarina.

PMID- 21855062
TI  - Pre-processing of data coming from a laser-EMAT system for non-destructive
      testing of steel slabs.
AB  - Non destructive test systems are increasingly applied in the industrial context
      for their strong potentialities in improving and standardizing quality control.
      Especially in the intermediate manufacturing stages, early detection of defects
      on semi-finished products allow their direction towards later production
      processes according to their quality, with consequent considerable savings in
      time, energy, materials and work. However, the raw data coming from non
      destructive test systems are not always immediately suitable for sophisticated
      defect detection algorithms, due to noise and disturbances which are unavoidable,
      especially in harsh operating conditions, such as the ones which are typical of
      the steelmaking cycle. The paper describes some pre-processing operations which
      are required in order to exploit the data coming from a non destructive test
      system. Such a system is based on the joint exploitation of Laser and Electro
      Magnetic Acoustic Transducer technologies and is applied to the detection of
      surface and sub-surface cracks in cold and hot steel slabs.

PMID- 21855063
TI  - Standardised cement augmentation of the PFNA using a perforated blade: A new
      technique and preliminary clinical results. A prospective multicentre trial.
AB  - Pertrochanteric fractures are a rising major health-care problem in the elderly
      and their operative stabilisation techniques are still under discussion.
      Furthermore, complications like cut-out are reported to be high and implant
      failure often is associated with poor bone quality. The PFNA((r)) with perforated
      blade offers a possibility for standardised cement augmentation using a
      polymethylmethacrylate (PMMA) cement which is injected through the perforated
      blade to enlarge the load-bearing surface and to diminish the stresses on the
      trabecular bone. The current prospective multicentre study was undertaken to
      evaluate the technical performance and the early clinical results of this new
      device. In nine European clinics, 59 patients (45 female, mean age 84.5 years)
      suffering from an osteoporotic pertrochanteric fracture (Arbeitsgemeinschaft fur
      Osteosynthesefragen, AO-31) were treated with the augmented PFNA((r)). Primary
      objectives were assessment of operative and postoperative complications, whereas
      activities of daily living, pain, mobility and radiologic parameters, such as
      cement distribution around the blade and the cortical thickness index, were
      secondary objectives. The mean follow-up time was 4 months where we observed
      callus healing in all cases. The surgical complication rate was 3.4% with no
      complication related to the cement augmentation. More than one-half of the
      patients reached their prefracture mobility level within the study period. A mean
      volume of 4.2ml of cement was injected. We did not find any cut-out, cut through,
      unexpected blade migration, implant loosening or implant breakage within the
      study period. Our findings lead us to conclude that the standardised cement
      augmentation using the perforated blade for pertrochanteric fracture fixation
      enhances the implant anchorage within the head-neck fragment and leads to good
      functional results.

PMID- 21855064
TI  - Blast-related mild traumatic brain injury is associated with a decline in self
      rated health amongst US military personnel.
AB  - INTRODUCTION: Mild traumatic brain injury (MTBI) has emerged as the preeminent
      injury of combat from the recent conflicts in Iraq and Afghanistan. Very little
      is known about short- and long-term outcomes after combat-related MTBI. As a
      measure of outcome after injury, self-rated health is a reliable, widely used
      measure that assesses perceived health. The primary aim of this study was to
      determine the effect of combat-related MTBI on self-reported health status after
      return from deployment. The secondary objective was to examine predictors of a
      decline in self-reported health status amongst US service members with MTBI, as
      compared to those service members with other minor non-TBI injuries. PATIENTS AND
      METHODS: MTBI cases and an injured comparison group were identified from the
      Expeditionary Medical Encounter Database records of 1129 male, US service members
      who experienced blast-related injuries in Iraq from March 2004 to March 2008.
      Self-rated health was assessed from the routinely administered pre- and post
      deployment health assessment questionnaires by the following question, "Overall,
      how would you rate your health during the past month?" Possible responses were
      "poor", "fair", "good", "very good", or "excellent." A distinction was made
      between minor and major negative changes in health (i.e., very good to fair)
      based on these self-rated health outcomes captured post-injury. RESULTS: For all
      personnel, post-injury levels of self-rated health were statistically
      significantly worse than pre-injury health rating. At 6months post-injury,
      service members with MTBI were 5 times more likely to report a major negative
      change in health as compared to members with other mild injuries. This
      association was independent of age, rank, branch of service, Injury Severity
      Score, mental health diagnosis prior to injury, and having been referred to a
      health care professional. DISCUSSION: Blast-related injuries, specifically MTBI,
      during deployment have negative consequences on service members' perception of
      health. Future research is needed to improve our understanding of the overall
      effects of MTBI on health and quality of life.

PMID- 21855065
TI  - Indicators for availability, utilization, and quality of emergency obstetric care
      in Ethiopia, 2008.
AB  - OBJECTIVE: To report on the availability and quality of emergency obstetric and
      newborn care (EmONC) in Ethiopia. METHODS: All licensed hospitals and health
      centers were visited and standard questionnaires were administered. In addition,
      a nonrandom systematic sample was taken of recent cesarean deliveries,
      partographs, and maternal deaths-and these cases were systematically reviewed.
      Health facilities were geocoded using geographic positioning system devices.
      RESULTS: Too few facilities provided EmONC to meet the UN standards of 5 per
      500,000 population, both nationally and in all but 2 regions. Only 7% of
      deliveries took place in institutions of any type, and only 3% in facilities that
      routinely provided all the signal functions. Only 6% of women with obstetric
      complications were treated in any health facility, half of whom were treated in
      fully functional EmONC facilities. Nationwide, 0.6% of expected deliveries were
      by cesarean. The mortality rate for women with serious obstetric complications
      (case fatality rate) was 2%. The cause of death was unknown in 10% of cases, and
      21% were due to indirect causes (primarily malaria, anemia, and HIV-related).
      CONCLUSION: None of the indicators met UN standards. Ethiopia faces many
      challenges--not least geography--with regard to improving EmONC. Nevertheless,
      the government places high priority on improvement and has taken (and will
      continue to take) action to achieve Millennium Development Goals 4 and 5. This
      comprehensive survey serves both as a road map for planning strategies for
      improvement and as a baseline for measuring the impact of interventions.

PMID- 21855066
TI  - A sexual health care attitude scale for nurses: development and psychometric
      evaluation.
AB  - BACKGROUND: Oncology nurses should possess a high level of sensitivity while
      dealing with patients' sexual health needs. However, sexual health care is still
      inadequately addressed because of barriers such as conservative beliefs and
      incorrect assumptions regarding sexual issues. Most scales for measuring attitude
      toward sexual health care were insufficient to establish the instrument's
      validity and did not focus on oncology nurses. AIMS AND OBJECTIVE: The purpose of
      this study was to develop a scale considering cultural contexts to investigate
      nurses' attitude toward sexual health care in patients suffering from cancer.
      DESIGN: This study was designed for scale development. METHODS: A preliminary
      version of the instrument was developed through a literature review and
      interviews with 10 oncology nurses; this version consisted of 42 items rated on a
      3-point scale. Eight experts reviewed the questionnaire for content validity and
      consolidated 36 items. Data were collected from 342 oncology nurses in Korea.
      Exploratory factor analysis was performed, and reliability was assessed using
      Cronbach alpha values. Pearson correlation coefficients were used to test the
      concurrent validity. RESULTS: Exploratory factor analysis revealed 17 items (4
      factors), which account for 70.49% of the total variance. The 4 factors were (1)
      discomfort in providing sexual health care (7 items), (2) feeling uncertain about
      patient's acceptance (4 items), (3) afraid of colleagues' negative response (3
      items), and (4) lack of environmental support (3 items). Correlation of the sub
      factors ranged from 0.35 to 0.63. The Cronbach alpha value was 0.92. Significant
      negative correlations were found between the attitude toward sexual health care
      and the Sexuality Attitudes and Belief Survey (r=-0.57, p<0.001). CONCLUSION: The
      scale of attitude toward sexual health care showed validity and reliability in
      evaluating the attitude of oncology nurses toward sexual health care and can be
      used to identify attitudinal barriers in nurses as well as to develop and test
      educational interventions for the improvement of sexual health care.

PMID- 21855067
TI  - Meta-analysis of the association between single nucleotide polymorphisms in TGF
      beta receptor genes and abdominal aortic aneurysm.
AB  - OBJECTIVE: The role of transforming growth factor (TGF)-beta in abdominal aortic
      aneurysm (AAA) is controversial. The aim of this study was to assess the
      association of single nucleotide polymorphisms (SNPs) within TGFBR1 and TGFBR2
      with AAA and infrarenal aortic diameter by combining data from previously
      published studies. METHODS: We performed a meta-analysis using individual subject
      data from three independent case-control groups from Western Australia (n=1675),
      New Zealand (n=1209), and the Netherlands (n=1636) with 610, 601, and 693 cases
      of AAA (maximum infrarenal aortic diameter >=30 mm), respectively. Data were
      available for two TGFBR1 (rs10819634, rs1571590) and six TGFBR2 (rs304839,
      rs1346907, rs1036095, rs9831477, rs9843143, rs764522) SNPs. RESULTS: There was
      marked heterogeneity between studies. The G alleles of the TGFBR2 rs764522 and
      rs1036095 SNPs were associated with AAA under a recessive model (OR=1.69, 95% CI
      1.28-2.25, P<0.001 and OR=1.59, 95% CI 1.23-2.07, P<0.001) when a fixed effects
      model was used. Both associations remained significant after adjustment for
      multiple testing. CONCLUSION: This study suggests that two common genetic
      polymorphisms in TGFBR2 are associated with the risk of developing AAA although
      this association was mainly driven by findings in the Netherlands group and
      marked between study heterogeneity was detected.

PMID- 21855068
TI  - Association of statins with inflammatory cytokines: a population-based Colaus
      study.
AB  - PURPOSE: A pleiotropic effect of statins has been reported in numerous studies.
      However, the association between statin use and inflammatory cytokines is
      controversial. We examined the associations between statin use and C-reactive
      protein (CRP), tumour necrosis factor alpha (TNF-alpha), interleukin-1beta (IL
      1beta) and interleukin-6 (IL-6) in a healthy Caucasian population. METHODS: Cross
      sectional study of 6184 participants aged 35-75 years from Lausanne, Switzerland.
      Cytokines were assessed by multiplexed particle-based flow cytometric assay. Self
      reported history of medication was collected for statins and other medication. 99
      participants without cytokine data were excluded. RESULTS: Among the 6085
      participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1beta, IL-6 and TNF
      alpha levels below detection limits, respectively. On multivariate analysis
      adjusting for age, gender, smoking status, body mass index, hypertension,
      diabetes, baseline cardiovascular disease, total cholesterol, anti-inflammatory
      use, other cytokine modifying drugs and other drugs, participants on statins had
      significantly lower CRP levels (adjusted mean+/-standard error: 1.22+/-1.05 vs.
      1.38+/-1.04 mg/L for use and non-use, respectively, p<0.01 on log-transformed
      data). Conversely, no association was found between statin use and IL-1beta
      (p=0.91), IL-6 (p=0.25) or TNF-alpha (p=0.28) levels. On multivariate analysis,
      individuals in the statin group (beta coefficient=-0.12; 95% CI=-0.21, -0.03) had
      lower levels of CRP as compared to those in the reference group (i.e. those not
      using statin). However, no significant associations were observed between IL
      1beta, IL-6 and TNF-alpha and statins. CONCLUSION: Individuals on statins have
      lower CRP levels; conversely, no effect was found for IL-1beta, IL-6 and TNF
      alpha levels.

PMID- 21855070
TI  - Bi-level optimizing control of a simulated moving bed process with nonlinear
      adsorption isotherms.
AB  - A bi-level optimizing control scheme originally proposed for a simulated moving
      bed (SMB) with linear isotherms has been extended to an SMB with nonlinear
      isotherms. Cyclic steady state optimization is performed in the upper level to
      determine the optimum switching period and time-varying feed/desorbent flow
      rates, and repetitive model predictive control is run in the lower level for
      purity regulation, taking the decision variables from the upper level as feed
      forward information. Experimental as well as numerical study for an SMB process
      separating a high-concentration mixture of aqueous L-ribose and L-arabinose
      solutions showed that the proposed scheme performs satisfactorily against various
      disturbances. In contrast, an alternative scheme based on an SMB model with
      linear isotherms showed a limitation in the control performance; this scheme was
      apt to fail in purity regulation.

PMID- 21855069
TI  - Impaired CXCR4 expression and cell engraftment of bone marrow-derived cells from
      aged atherogenic mice.
AB  - OBJECTIVES: Reduced numbers and activity of circulating progenitor cells are
      associated with aging and have been linked with coronary artery disease. To
      determine the impact of aging and atherosclerotic disease on the chemotaxic
      activity of bone marrow derived cells (BMCs), we examined CXCR4 surface
      expression on BMCs from aged and atherosclerotic mice. METHODS: CXCR4 expression
      and cellular mobility were compared between BMCs of young (6-week old) ApoE null
      mice (ApoE(-/-)) and aged ApoE(-/-) mice that had been fed with a high-fat, high
      cholesterol diet for 6-months. RESULTS: Age and atherosclerosis correlated with
      significantly lower surface expression of CXCR4 that was less inducible by
      calcium. The impaired calcium response was associated with defective calcium
      influx and was partially recovered by treatment with the calcium ionophore
      ionomycin. ApoE(-/-) mice fed high fat diet for 6-months had defective CXCR4
      expression and SDF-1 regulation that is equivalent to that of 24-month old wild
      type mice. BMCs from aged, atherogenic ApoE(-/-) mice also displayed defective
      homing to SDF-1, and the animals had lower serum and bone marrow levels of SDF-1.
      CONCLUSION: Evolution of atherosclerosis in ApoE(-/-) mice is paralleled by
      progressive loss of mobility of BMCs with reductions of CXCR4 expression, and
      reduced levels of SDF-1 in both serum and bone marrow. These changes mute the
      homing capability of BMCs and may contribute to the progression of
      atherosclerosis in this model.

PMID- 21855071
TI  - Features for non-targeted cross-sample analysis with comprehensive two
      dimensional chromatography.
AB  - This review surveys different approaches for generating features from
      comprehensive two-dimensional chromatography for non-targeted cross-sample
      analysis. The goal of non-targeted cross-sample analysis is to discover relevant
      chemical characteristics (such as compositional similarities or differences) from
      multiple samples. In non-targeted analysis, the relevant characteristics are
      unknown, so individual features for all chemical constituents should be analyzed,
      not just those for targeted or selected analytes. Cross-sample analysis requires
      matching the corresponding features that characterize each constituent across
      multiple samples so that relevant characteristics or patterns can be recognized.
      Non-targeted, cross-sample analysis requires generating and matching all features
      across all samples. Applications of non-targeted cross-sample analysis include
      sample classification, chemical fingerprinting, monitoring, sample clustering,
      and chemical marker discovery. Comprehensive two-dimensional chromatography is a
      powerful technology for separating complex samples and so is well suited for non
      targeted cross-sample analysis. However, two-dimensional chromatographic data is
      typically large and complex, so the computational tasks of extracting and
      matching features for pattern recognition are challenging. This review examines
      five general approaches that researchers have applied to these difficult
      problems: visual image comparisons, datapoint feature analysis, peak feature
      analysis, region feature analysis, and peak-region feature analysis.

PMID- 21855072
TI  - Effect of pH on protein adsorption capacity of strong cation exchangers with
      grafted layer.
AB  - The effect of pH on the static adsorption capacity of immunoglobulin G, human
      serum albumin, and equine myoglobin was investigated for a set of five strong
      cation exchangers with the grafted tentacle layer having a different ligand
      density. A sharp maximum of adsorption capacity with pH was observed for
      adsorbents with a high ligand density. The results were elucidated using the
      protein structure and calculations of pK(a) of ionizable groups of surface basic
      residues. Inverse size-exclusion experiments were carried out to understand the
      relation between the adsorption capacity and pore accessibility of the
      investigated proteins.

PMID- 21855073
TI  - Comments on the separation efficiency of asymmetrical flow field-flow
      fractionation in channels of constant channel and crossflow velocities leading to
      constant separation efficiency.
AB  - It is shown theoretically that a claim in the literature about the overall
      separation efficiency of asymmetrical flow FFF channels being improved by
      geometries that permit a uniform channel flow velocity throughout the channel
      length is untrue.

PMID- 21855074
TI  - Quantification of 4-hydroxy-2,5-dimethyl-3-furanone in fruit samples using solid
      phase microextraction coupled with gas chromatography-mass spectrometry.
AB  - Furaneol is an important aroma compound. It is very difficult to extract furaneol
      from food matrices and separate it on a gas chromatography column due to its high
      polarity and instability. A new quantitative method was developed to quantify
      furaneol in aqueous samples by the use of derivatization/solid phase
      microextraction (SPME) coupled with gas chromatography/mass spectrometry (GC/MS).
      The derivatization was carried out by reacting pentafluorobenzyl bromide with
      furaneol in basic solutions at elevated temperatures. The derivative was stable
      and less polar so that SPME-GC/MS could be applied for extraction, separation and
      detection. The automated analytical method had a limit of detection (LOD) of 0.5
      ng mL(-1), a limit of quantification (LOQ) of 2 ng mL(-1), a repeatability of
      9.5%, and a linear range from 2 to 500 ng mL(-1). The method was applied to
      analyze fruit samples. And it was found that the concentrations of furaneol in
      tomato ranged from 95 to 173 MUg kg(-1), in strawberries ranged from 1663 to 4852
      MUg kg(-1). The results were verified with a LC procedure. To facilitate
      analytical method development, some physico-chemical parameters for furaneol were
      determined in this work. Its solubility in water was determined as 0.315 g mL(-1)
      (25 degrees C). Its LogD in water and LogP in 0.1 M phosphate buffer were -0.133
      and 0.95 (20  degrees C), respectively. Its pKa was 8.56 (20  degrees C).

PMID- 21855075
TI  - Molecularly imprinted polymer grafted to porous polyethylene frits: a new
      selective solid-phase extraction format.
AB  - In this paper, a novel format for selective solid-phase extraction based on a
      molecularly imprinted polymer (MIP) is described. A small amount of MIP has been
      synthesized within the pores of commercial polyethylene (PE) frits and attached
      to its surface using benzophenone (BP), a photo-initiator capable to start the
      polymerisation from the surface of the support material. Key properties affecting
      the obtainment of a proper polymeric layer, such as polymerisation time and kind
      of cross-linker were optimised. The developed imprinted material has been applied
      as a selective sorbent for cleaning extracts of thiabendazole (TBZ), as model
      compound, from citrus samples. The use of different solvents for loading the
      analyte in the imprinted frits was investigated, as well as the binding capacity
      of the imprinted polymer. Imprinted frits showed good selectivity when loads were
      performed using toluene and a linear relationship was obtained for the target
      analyte up to 1000 ng of loaded analyte. Prepared composite material was applied
      to the SPE of TBZ in real samples extracts, showing an impressive clean-up
      ability. Calibrations showed good linearity in the concentration range of 0.05
      5.00 MUg g(-1), referred to the original solid sample, and the regression
      coefficients obtained were greater than 0.996. The calculated detection limit was
      0.016 MUg g(-1), low enough to satisfactory analysis of TBZ in real samples. RSDs
      at different spiking levels ranged below 15% in all the cases and imprinted frits
      were reusable without loss in their performance.

PMID- 21855076
TI  - Effect of chromatographic conditions on liquid chromatographic chiral separation
      of terbutaline and salbutamol on Chirobiotic V column.
AB  - In this study, a method for enantioseparation of terbutaline and salbutamol was
      established using Chirobiotic V column as a stationary phase. Polar ionic mode
      applying mobile phase containing ammonium nitrate in 100% ethanol, pH 5.1 was
      found to give the best separation. The salt concentration in the mobile phase and
      pH value were found to be the most important chromatographic factors affecting
      separation. Separation of enantiomers of these two basic analytes was complete in
      less than 10 min without applying ammonium trifluoroacetate (ATFA) or
      triethylamine (TEA) salts.

PMID- 21855077
TI  - Comparison of the gradient kinetic performance of silica monolithic capillary
      columns with columns packed with 3 MUm porous and 2.7 MUm fused-core silica
      particles.
AB  - The kinetic-performance limits of a capillary silica C18 monolithic column and
      packed capillary columns with fully-porous 3 MUm and fused-core 2.7 MUm silica
      C18 particles (all 5 cm long) were determined in gradient-elution mode for the
      separation of peptides. To establish a kinetic plot in gradient-elution mode, the
      gradient time to column dead time ratio (t(G)/t0) was maintained constant when
      applying different flow rates. The normalized gradient approach was validated by
      dimensionless chromatograms, obtained at different flow rates and gradient times
      by plotting them as a function of the retention factor. The separation
      performance of the different column types was visualized via kinetic plots
      depicting the gradient time required to achieve a certain peak capacity when
      operating at a maximum system pressure of 350 bar. The gradient steepness
      (applying t(G)/t0=10, 20, and 40) did not significantly affect the gradient
      performance limits for low (< 250) peak-capacity separations. For high peak
      capacity separations the peak capacity per unit time increases when increasing
      the t(G)/t0 ratio. The C-term contribution of the porous 3 MUm and fused-core 2.7
      MUm was comparable yielding the same gradient kinetic-performance limits for fast
      separations at a column temperature of 60  degrees C. The capillary silica
      monolithic column showed the lowest contribution in mass transfer and
      permeability was higher than the packed columns. Hence, the silica monolith
      showed the best kinetic performance for both fast and high peak-capacity gradient
      separations.

PMID- 21855078
TI  - A 2H nuclear magnetic resonance study of the state of water in neat silica and
      zwitterionic stationary phases and its influence on the chromatographic retention
      characteristics in hydrophilic interaction high-performance liquid
      chromatography.
AB  - 2H NMR has been used as a tool for probing the state of water in hydrophilic
      stationary phases for liquid chromatography at temperatures between -80 and +4 
      degrees C. The fraction of water that remained unfrozen in four different neat
      silicas with nominal pore sizes between 60 and 300 A, and in silicas with
      polymeric sulfobetaine zwitterionic functionalities prepared in different ways,
      could be determined by measurements of the line widths and temperature-corrected
      integrals of the 2H signals. The phase transitions detected during thawing made
      it possible to estimate the amount of non-freezable water in each phase. A
      distinct difference was seen between the neat and modified silicas tested. For
      the neat silicas, the relationship between the freezing point depression and
      their pore size followed the expected Gibbs-Thomson relationship. The polymeric
      stationary phases were found to contain considerably higher amounts of non
      freezable water compared to the neat silica, which is attributed to the
      structural effect that the sulfobetaine polymers have on the water layer close to
      the stationary phase surface. The sulfobetaine stationary phases were used
      alongside the 100 A silica to separate a number of polar compounds in hydrophilic
      interaction (HILIC) mode, and the retention characteristics could be explained in
      terms of the surface water structure, as well as by the porous properties of the
      stationary phases. This provides solid evidence supporting a partitioning
      mechanism, or at least of the existence of an immobilized layer of water into
      which partitioning could be occurring.

PMID- 21855081
TI  - The effect of contact angle hysteresis on droplet coalescence and mixing.
AB  - In this work, droplet coalescence and the subsequent mixing in superhydrophobic
      surfaces is studied over a range of impact velocities and impact angles. Sanded
      Teflon surfaces are used as a novel two-dimensional microfluidics platform. These
      superhydrophobic surfaces exhibit a constant advancing contact angle of
      theta(A)=150 degrees  over a broad range of contact angle hysteresis. As a
      result, the effect of contact angle hysteresis on droplet coalescence and mixing
      can be studied. Based on the observed characteristics of coalescence, three
      different regimes of coalescence are identified as a function of both Weber
      number and impact angle. These regimes include oscillation dominated, rotation
      dominated, and mixed dynamics. It is shown that within Weber number ranges
      achievable in this experiment, hysteresis greatly reduces the deformation of the
      droplet coalescence process and the subsequent mixing. In head-on collisions,
      higher hysteresis is found to decrease the frequency at which the resulting dr
      oscillates. In the case of glancing collisions, where the resulting droplet is
      found to rotate, higher hysteresis increases the rate of rotation although the
      overall angular momentum is found to be independent of contact angle hysteresis.

PMID- 21855079
TI  - Gas chromatographic retention indices of trimethylsilyl derivatives of terpene
      alcohols.
AB  - This paper presents the experimentally determined retention indices (RI(TMS)) for
      a set of 75 silylated terpenols (33 monoterpenols and 42 sesquiterpenols). The
      attempt was made to assess the dependence of RI(TMS) on RI (for non-silylated
      terpenols) and on RI(Ac) (for acetylated terpenols). Satisfactory linear
      regression parameters (RI(TMS)=b(0)+b(1)RI) were observed for tertiary
      substituted monoterpenols and primary or secondary substituted sesquiterpenols.
      The mass spectra of silylated terpenols that were not found in the available
      literature are in Supplementary information.

PMID- 21855080
TI  - Fast high performance liquid chromatography separations for proteomic
      applications using Fused-Core(r) silica particles.
AB  - The separation range of superficially porous particles (Fused-Core(r)) has been
      extended by design of particles with 160 A pores. These particles show superior
      kinetics (lower resistance to mass transfer), allowing fast separations of
      peptides and small proteins (molecular weights of <15,000). The high efficiency
      and relatively low back pressure of these 2.7 MUm Fused-Core particles has been
      maintained so that separations can be performed with conventional HPLC
      instruments. Longer columns can be used for higher resolution of complex mixtures
      of peptides, such as proteolytic digests. Highly reproducible separations of
      peptides at elevated temperatures with low pH mobile phases are maintained as a
      result of a stable bonded stationary phase. The utility of such highly stable
      materials is exemplified by separations of problematic amyloid peptides at low pH
      (TFA mobile phase) at an operational temperature of 100  degrees C. To address
      the issue of poor peptide peak shape in formic acid-containing mobile phases we
      show that the addition of 10-20 mM ammonium formate improves peak shape,
      retention and load tolerance of peptides. Use of the Fused-Core particle
      materials for separations of synthetic peptides and tryptic digests yields peak
      capacities that are comparable to those obtained using columns packed with sub-2
      MUm particles, but with less than one-half of the operating back pressure. A peak
      capacity of 530 was obtained in 150 min on coupled columns of HALO Peptide ES-C18
      with a combined length of 250 mm.

PMID- 21855082
TI  - Metal-ion retention properties of water-soluble amphiphilic block copolymer in
      double emulsion systems (w/o/w) stabilized by non-ionic surfactants.
AB  - Metal-ion retention properties of water-soluble amphiphilic polymers in presence
      of double emulsion were studied by diafiltration. Double emulsion systems, water
      in-oil-in-water, with a pH gradient between external and internal aqueous phases
      were prepared. A poly(styrene-co-maleic anhydride) (PSAM) solution at pH 6.0 was
      added to the external aqueous phase of double emulsion and by application of
      pressure a divalent metal-ion stream was continuously added. Metal-ions used were
      Cu(2+) and Cd(2+) at the same pH of polymer solution. According to our results,
      metal-ion retention is mainly the result of polymer-metal interaction.
      Interaction between PSMA and reverse emulsion globules is strongly controlled by
      amount of metal-ions added in the external aqueous phase. In addition, as metal
      ion concentration was increased, a negative effect on polymer retention capacity
      and promotion of flocculation phenomena were produced.

PMID- 21855083
TI  - Adsorption-desorption mechanism of phosphate by immobilized nano-sized magnetite
      layer: interface and bulk interactions.
AB  - Phosphate adsorption mechanism by a homogenous porous layer of nano-sized
      magnetite particles immobilized onto granular activated carbon (nFe-GAC) was
      studied for both interface and bulk structures. X-ray Photoelectron Spectroscopy
      (XPS) analysis revealed phosphate bonding to the nFe-GAC predominantly through
      bidentate surface complexes. It was established that phosphate was adsorbed to
      the magnetite surface mainly via ligand exchange mechanism. Initially, phosphate
      was adsorbed by the active sites on the magnetite surface, after which it
      diffused into the interior of the nano-magnetite layer, as indicated by
      intraparticle diffusion model. This diffusion process continues regardless of
      interface interactions, revealing some of the outer magnetite binding sites for
      further phosphate uptake. Desorption, using NaOH solution, was found to be
      predominantly a surface reaction, at which hydroxyl ions replace the adsorbed
      phosphate ions only at the surface outer biding sites. Five successive fix-bed
      adsorption/regeneration cycles were successfully applied, without significant
      reduction in the nFe-GAC adsorption capacity and at high regeneration efficiency.

PMID- 21855084
TI  - Effect of submicron particles on electrowetting on dielectrics (EWOD) of sessile
      droplets.
AB  - The present study elucidates the effects of included submicron-sized particles on
      the wetting behavior of sessile droplets under the influence of applied electric
      field in an electro-wetting-on-dielectric (EWOD) configuration. A thermodynamic
      description using an energy minimization approach is used to analyze the
      experimental results related to the effects of the included particles on the EWOD
      phenomenon, considering the effects of line tension as well. The effects of
      particle size and concentration on interfacial areas are included in the model to
      analyze the wetting characteristics. Experiments are also conducted with
      submicron-sizes latex beads, in an effort to elucidate the related phenomena. It
      is further postulated that these beads act as suspended dielectrics in the
      droplet, thereby mimicking a system of two capacitors in series. An effective
      electrical permittivity of the composite medium is used to study the experimental
      results related to contact angle changes at different concentrations and
      diameters of submicron particles in the droplet.

PMID- 21855086
TI  - Bivariate phase-rectified signal averaging for assessment of spontaneous
      baroreflex sensitivity: normalization of the results.
AB  - BACKGROUND: Previously proposed technique for assessment of spontaneous
      baroreflex sensitivity (BRS) based on bivariate phase-rectified signal averaging
      measures averaged R-R interval (RRI) changes triggered by beat-to-beat increases
      in systolic blood pressure (SBP). In this study, we investigate a normalized
      version of the method that relates the averaged RRI changes to the triggering
      blood pressure changes, thus providing the results in measurement units
      comparable with existing literature. METHODS: Data of previously reported
      prospective observational study were used. In each of 146 heart failure patients
      presenting with sinus rhythm, 10-minute recordings of electrocardiogram and
      arterial and blood pressures were obtained in the supine resting position. The
      averaged RRI increases initiated by beat-to-beat SBP increases were measured
      (original BRS result in milliseconds) and normalized for the averaged beat-to
      beat SBP increases (normalized BRS result in milliseconds per millimeters of
      mercury). Both results were compared in terms of predicting all-cause mortality
      during a mean follow-up of 2.7 +/- 1.1 years when 42 patients (28.8%) died.
      RESULTS: Both types of results were highly correlated (r = 0.938, P < .001) and
      led to similarly strong separation of high- and low-risk groups. The receiver
      operator characteristics of both indices were well within the 95% confidence
      intervals of each other, and the areas under the characteristics were practically
      identical: 71.1% (95% confidence interval, 60.7%-80.9%) for original BRS and
      69.7% (58.9%-79.2%) for normalized BRS. CONCLUSION: The results might question
      the concept of a linear relationship between the SBP changes and RRI changes. The
      phase-rectified signal averaging-based assessment of BRS may be used with equal
      legitimacy in the nonnormalized and normalized forms; the normalized form
      provides results in conventional measurement units.

PMID- 21855085
TI  - Widening spectrum of the J-wave syndromes.

PMID- 21855087
TI  - Epilepsy and Behcet's disease: cortical and hippocampal involvement in Brazilian
      patients.
AB  - OBJECTIVE: To describe clinical, radiological and electrophysiological findings
      in epileptic neuro-Behcet's (NBD) patients. METHODS: A retrospective review of
      178 medical records of Behcet's disease patients was conducted in Brazil.
      Information on gender, ethnicity/skin color, age at symptom onset and age at
      onset of neurologic manifestations, type of seizures, clinical manifestation of
      the disease, use of antiepileptic drugs and immunosupressors was collected from
      medical records of all epileptic NBD patients. Brain MRI, cerebrospinal fluid
      (CSF) analysis and electroencephalograms (EEG) were assessed. RESULTS: Forty NBD
      cases were identified, of which seven patients (17%) presented epilepsy. In five
      patients seizures occurred during an acute exacerbation of the disease, and in
      one patient they occurred six months after meningoencephalitis. One patient
      presented seizures in the progressive form of the disease and five patients had
      complex partial seizures. The EEG showed temporal involvement in three patients
      and frontal in one. Hippocampal lesions were identified in three patients and
      cortical lesions in five. All patients had good response to antiepileptic drugs
      and are seizure-free, except for one who developed refractory seizures.
      CONCLUSIONS: Brazilian NBD patients showed a high prevalence of epilepsy, mainly
      complex partial seizures, occurring at any phase of the disease. Epileptic NBD
      patients may have cortical and hippocampal lesions that could explain the
      occurrence of epilepsy.

PMID- 21855089
TI  - Intraoperative hypotension, new onset atrial fibrillation, and adverse outcome
      after carotid endarterectomy.
AB  - BACKGROUND: Information regarding predisposing factors, frequency, and prognostic
      implications of new onset atrial fibrillation (NOAF) after carotid endarterectomy
      (CEA) is scarce. We assessed the frequency, risk factors, and the prognostic
      impact of NOAF after CEA. METHODS: We assessed every patient undergoing CEA (n =
      186) at our academic hospital between 2006 and 2009. Patients underwent
      continuous electrocardiographic monitoring during surgery and during the rest of
      hospital stay. We performed univariate and multivariate analyses for identifying
      variables associated with NOAF and for individualizing variables related to four
      perioperative adverse outcome measures: a) ischemic stroke; b) ischemic stroke
      and myocardial infarction, c) ischemic stroke and death, and d) ischemic stroke,
      myocardial infarction, and death. RESULTS: The study cohort comprised 186
      patients. Overall, NOAF was detected in 7 cases (3.8%). The only variable
      associated with NOAF was intraoperative hypotension (OR 9.6, 95% CI 1.9-47.4, P =
      .006). There were no perioperative deaths. NOAF was associated with perioperative
      ischemic stroke and with the combined outcome of ischemic stroke and myocardial
      infarction. CONCLUSIONS: We found a low frequency of NOAF after CEA.
      Intraoperative hypotension was associated to a higher risk of NOAF. In turn, NOAF
      was related to adverse postoperative outcome. Further research is needed to
      clarify the pathophysiological relation between intraoperative hypotension, NOAF,
      and adverse CEA outcome.

PMID- 21855088
TI  - A novel mutation in the calcium channel gene in a family with hypokalemic
      periodic paralysis.
AB  - Hypokalemic periodic paralysis (HypoPP) type 1 is an autosomal dominant disease
      caused by mutations in the Ca(V)1.1 calcium channel encoded by the CACNA1S gene.
      Only seven mutations have been found since the discovery of the causative gene in
      1994. We describe a patient with HypoPP who had a high serum potassium
      concentration after recovery from a recent paralysis, which complicated the
      correct diagnosis. This patient and other affected family members had a novel
      mutation, p.Arg900Gly, in the CACNA1S gene.

PMID- 21855090
TI  - Community acquired Staphylococcus aureus meningitis and cerebral abscesses in a
      patient with a hyper-IgE and a Dubowitz-like syndrome.
AB  - The Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency which recently
      has been associated with heterozygous dominant-negative mutations in the signal
      transducer and activator of transcription 3 (STAT3). Although HIES is
      characterized by recurrent staphylococcal infections, the microbial invasion of
      the central nervous system (CNS) is definitively uncommon. We here report on
      Staphylococcus aureus meningitis and cerebral abscesses acquired in the community
      in a 31-year-old female patient with a de novo heterozygous mutation of STAT3 and
      a Dubowitz-like syndrome characterized by growth retardation, microcephaly and
      eczema. The patient presented with a relative paucity of clinical symptoms
      despite severe cerebrospinal fluid pathology and multiple cerebral abscesses.
      Antimicrobial as well as treatment with intravenous immunoglobulin was well
      tolerated and led to a slow recovery over a 6 months period. Our observation adds
      community acquired S. aureus meningitis to the list of life-threatening
      infections in STAT3-deficient HIES and should also raise awareness for the
      unusual clinical presentation of severe neuroinfection in this syndrome. Whether
      the association of HIES with Dubowitz-like syndrome was purely coincidental,
      possibly supportive of the CNS infection, or suggests a genetic overlap of these
      syndromes, awaits clarification.

PMID- 21855091
TI  - Preoperative aortic root geometry and postoperative cusp configuration primarily
      determine long-term outcome after valve-preserving aortic root repair.
AB  - OBJECTIVE: Technical controversies exist in valve-preserving aortic root
      replacement. We sought to determine predictors of long-term stability of the
      aortic valve. METHODS: A total of 430 patients (aged 57 +/- 15 years, 323 male)
      underwent valve-preserving aortic root surgery (remodeling in 401, reimplantation
      in 29) between 1995 and 2009 and were followed echocardiographically. Factors
      influencing late recurrence of aortic valve regurgitation grade II or greater (n
      = 45) or need for reoperation on the aortic valve (n = 25) were analyzed.
      RESULTS: Early mortality was 2.8% (1.9% for elective cases), and actuarial
      survival at 10 years was 83.5% +/- 2.4%. Ten-year freedom from aortic valve
      regurgitation grade II or greater was 85.0% +/- 2.5%. Preoperative
      aortoventricular junction diameter greater than 28 mm and postoperative effective
      height of the aortic cusp less than 9 mm were identified as significant
      predictors for late aortic valve regurgitation grade II or greater in
      multivariate analysis (both P < .001). Ten-year freedom from reoperation on the
      aortic valve was 89.3% +/- 2.5%. Preoperative aortoventricular junction diameter
      greater than 28 mm (P < .001), use of pericardial patch (P = .022), and effective
      height of the aortic cusp less than 9 mm (P = .049) were identified as
      significant predictors for reoperation in multivariate analysis. Operative
      technique (remodeling, reimplantation), Marfan syndrome, bicuspid valve anatomy,
      concomitant central cusp plication, size of prosthesis used, and acute dissection
      were not associated with an increased risk of late aortic valve regurgitation
      grade II or greater or reoperation. In patients with preoperative
      aortoventricular junction diameter greater than 28 mm (n = 94), the addition of
      central cusp plication significantly improved freedom from aortic valve
      regurgitation grade II or greater (P = .006) regardless of root procedures
      (remodeling, P = .011; reimplantation, P = .053). CONCLUSIONS: Long-term
      stability of valve-preserving aortic root replacement was influenced not by the
      technique of root repair but by the preoperative aortic root geometry and
      postoperative cusp configuration.

PMID- 21855092
TI  - Anomalous left coronary artery from the right pulmonary artery with aortic
      fusion.

PMID- 21855093
TI  - A novel cardioport for beating-heart, image-guided intracardiac surgery.
AB  - OBJECTIVE: Intracardiac beating-heart procedures require the introduction and
      exchange of complex instruments and devices. To prevent potential complications
      such as air embolism and bleeding, a universal cardioport was designed and
      tested. METHODS: The design consists of a port body and a series of
      interchangeable sleeves. The port uses a fluid purging system to remove air from
      the instrument before insertion into the heart, and a valve system minimizes
      blood loss during instrument changes. RESULTS: The cardioport was tested ex vivo
      and in vivo in pigs (n = 5). Beating-heart procedures, such as septal defect
      closure and mitral valve repair, were modeled. Ex vivo trials (n = 150) were
      performed, and no air emboli were introduced using the port. In comparison, air
      emboli were detected in 40% to 85% of the cases without the use of the port-based
      purging system. Port operation revealed excellent ergonomics and minimal blood
      loss. CONCLUSIONS: A novel cardioport system designed to prevent air entry and
      blood loss from transcardiac instrument introduction was shown to be an enabling
      platform for intracardiac beating-heart surgery. The port system improves safety
      and facilitates further development of complex instruments and devices for
      transcardiac beating-heart surgery.

PMID- 21855094
TI  - Structural deterioration of the cryopreserved mitral homograft valve.
AB  - OBJECTIVE: The aim of this study was to evaluate the long-term fate of the
      cryopreserved mitral homograft focusing on structural valve deterioration.
      METHODS: Homograft replacement of the mitral valve was performed in 106 patients.
      The causes of mitral disease were rheumatic disease (n=75), endocarditis (n=24),
      and others (n=7). There were 40 partial homografts and 66 total homografts.
      RESULTS: Mean follow-up was 9.3+4.7 years (up to 17.8 years). There were 5 early
      (<3 months) and 15 late deaths. There have been 5 early (<3 months) and 30 late
      reoperations. Five patients had endocarditis, and 5 patients had an
      ischemic/hemorrhagic event. Compared with baseline, follow-up echography showed
      progression of mitral regurgitation grade (from 0.4 to 1.3; P<.001) with stenosis
      (elevated gradient: from 3.9 to 7.0 mm Hg; P<.001) and decreased valve area (from
      2.3 to 1.7 cm2, P<.001). Freedom from structural valve deterioration was 90%,
      76%, and 65% at 5, 10, and 15 years, respectively. Structural valve deterioration
      was more frequent in total homografts (P=.018 vs partial homografts) and in case
      of pregnancy (P=.016 vs no pregnancy). Stenosis related to structural valve
      deterioration was more pronounced for age less than 40 years (P=.03) and ring
      size 30 mm or less (P=.002). Pathologic analysis of the explanted homografts
      almost invariably showed dense fibrosis with calcification and no cellularity.
      CONCLUSIONS: Mitral homografting was accomplished with early echographic results
      similar to those of valve repair. Structural valve deterioration produced mixed
      stenosis with insufficiency, and its incidence was comparable to that of
      bioprostheses structural valve deterioration. An improvement in the preservation
      mode of valvular homografts is warranted.

PMID- 21855095
TI  - Outcome after repair of atrioventricular septal defect with tetralogy of Fallot.
AB  - BACKGROUND: Long-term outcomes of repair of tetralogy of Fallot associated with
      complete atrioventricular septal defect are seldom reported. We report our
      survival and reintervention outcomes over a 29-year time period. METHODS: Between
      March 1979 and April 2008, 61 patients with the combined cardiac defect of
      atrioventricular septal defect and tetralogy of Fallot were surgically managed.
      Trisomy 21 was present in 49 (80%) patients. Primary repair was performed in 36
      patients at a median age of 9 months (range, 1 month to 16 years), whereas 25
      patients had initial palliation by systemic-pulmonary shunt at a median age of 21
      months (range, 0 days to 36 years). Thirty-one (51%) patients had a transannular
      patch. Fifty-three patients required right ventriculotomy for relief of the right
      ventricular outflow tract obstruction. Four patients had a right ventricle
      pulmonary artery conduit with a homograft. Relationships between patient
      characteristics and outcome variables were examined using Kaplan-Meier survival
      curves; comparisons were performed using the log-rank test. RESULTS: Median
      follow-up was 4.7 years. A total of 12 patients died during the course of follow
      up: 4 (7%)deaths within 30 days of surgery and 8 late deaths (range, 4 months to
      9.9 years after repair). Since 2000, there have been no early deaths and 1 late
      death, 5 months after the operation. The estimated survival at 5 years after
      definitive repair was 82% (95% confidence interval, 69%, 90%). Time to death was
      not associated with any patient or surgical variables examined. Overall, 30% of
      the survivors required a reoperation. The type of reoperations was on the mitral
      valve (4 repairs, 4 replacements) and 7 pulmonary valve replacements. We did not
      find an effect of era on mortality (P = .23 for comparison of 1979-1989, 1990
      1999, and 2000-2008). The percentage of patients with primary repair did not
      change during the different quartiles. The estimated freedom from reoperation at
      5 years was 80% (65%, 90%). Time to reoperation was shorter for patients with a
      conduit (P = .01). CONCLUSIONS: Excellent long-term survival was achieved after
      repair of tetralogy of Fallot associated with complete atrioventricular septal
      defect. Palliation and primary repair resulted in comparable outcomes; as such,
      primary repair is favored. The choice of right ventricular outflow tract
      reconstruction affects the need for reoperation.

PMID- 21855096
TI  - Income inequality and population health in Islamic countries.
AB  - OBJECTIVES: To undertake a fresh examination of the relationship between income
      inequality and population health for a group of Islamic countries using recent
      information derived from data resource sites from the World Bank and Islamic
      countries. STUDY DESIGN: Cross-sectional data on different measures of income
      distribution (prosperity, health care, women's role and environment) and
      indicators of population health were used to illuminate this issue. METHODS: The
      relationship between income inequality and population health for a group of
      Islamic countries was tested using recent information derived from data resource
      sites from the World Bank and Islamic countries. After consideration of previous
      studies, seven dependent variables were determined and tested in six equation
      formats. RESULTS: According to the equations, the urban population percentage and
      gross domestic product are the most important significant variables that affect
      life expectancy and the infant mortality rate in Islamic countries. The income
      distribution coefficient, regardless of the type of measure, was almost
      insignificant in all equations. CONCLUSIONS: In selected Islamic countries,
      income level has a positive effect on population health, but the level of income
      distribution is not significant. Among the other dependent variables (e.g.
      different measures of income distribution, health care, role of women and
      environment), only environment and education had significant effects. Most of the
      Islamic countries studied are considered to be poorly developed.

PMID- 21855097
TI  - Chronic disease and health behaviours linked to experiences of non-consensual sex
      among women and men.
AB  - OBJECTIVES: Few studies have examined the association between non-consensual sex
      and health indicators for both women and men. The current study examined this
      relationship as part of a large public health survey that collected information
      on a range of health behaviours and health risks. METHODS: The Behavioural Risk
      Factor Surveillance System (BRFSS) is an annual random-digit-dialled telephone
      survey providing surveillance of health behaviours and health risks among US
      adults. In 2005, an optional module on sexual violence was available for use at
      the discretion of each US state/territory. Over 115,000 respondents in 25
      states/territories were administered the sexual violence module within the BRFSS.
      Logistic regression analyses were conducted from January to December 2008.
      RESULTS: Among both women and men, previous non-consensual sex was associated
      with health conditions such as high cholesterol, stroke and heart disease, and
      risk behaviours such as human immunodeficiency virus risk factors, smoking and
      excessive drinking. Sexually victimized women were more likely to report having
      had a heart attack or heart disease than non-victims. CONCLUSIONS: The experience
      of non-consensual sex is associated with a number of chronic disease outcomes and
      risk factors. The development and implementation of effective sexual violence
      prevention strategies may reduce the risk of chronic conditions among persons who
      have experienced sexual victimisation.

PMID- 21855098
TI  - Exploratory study to evaluate the provision of additional midwifery support to
      teenage mothers.
AB  - OBJECTIVE: To evaluate the provision of psychosocial interventions of potential
      benefit to pregnant teenage women. STUDY DESIGN: Pre-test/post-test, controlled,
      experimental design. METHODS: One hundred and sixty-four pregnant teenage women
      received usual midwifery care or usual midwifery care plus additional
      psychosocial support. Four outcomes were measured at baseline and 4 weeks after
      delivery: self-esteem (Rosenberg Self-Esteem Scale), physical activity
      (International Physical Activity Questionnaire), social support (Short Form
      Social Support Questionnaire) and smoking behaviour (yes/no). RESULTS: At follow
      up, there were no significant differences in any of these outcomes between the 65
      women in the intervention group and the 64 women in the control group who
      completed both assessments (mean age 17.5 years). There was no difference in use
      of National Health Service (NHS) services, but the intervention group made
      greater use of non-NHS services, such as family planning or help with housing or
      benefits problems. CONCLUSION: The very low self-esteem of the women in the study
      may indicate that the intervention was not sufficiently robust to impact on
      mental health and lifestyle, although a longer follow-up may be needed to confirm
      this. Discrepancy in the evidence provided by formal and informal data suggests
      that project benefits may have been more evident if the evaluation had included a
      qualitative element to address the complexity of the client group and
      intervention.

PMID- 21855099
TI  - How well do strategic environmental assessments in Scotland consider human
      health?
AB  - OBJECTIVES: Strategic environmental assessment (SEA) is a systematic approach to
      identifying, describing, evaluating and reporting on the environmental - and
      health - effects of policies, plans and strategies. SEAs have potential to
      improve population health because they assess 'upstream' health determinants and
      recommend measures to improve these. The authors studied the range of health
      issues considered in SEAs in Scotland, and the evidence used in their assessment.
      STUDY DESIGN: Documentary review of 62 consecutive SEA reports. METHODS:
      Environmental reports were categorized by sector, and the health-related
      environmental problems, SEA objectives/criteria, differential impacts, evidence,
      recommended mitigation and monitoring were identified for each report. RESULTS:
      Environmental reports identified many health-related issues, and set a wide range
      of health-related objectives/criteria, but these were inconsistent for SEAs
      assessing similar plans. Few identified differential impacts or mental health
      impacts. Mitigation focused on mitigating adverse impacts rather than enhancing
      positive impacts. It was unclear what health evidence was used to inform the
      judgements made in scoring the plans against SEA objectives. CONCLUSIONS: Many
      SEAs in Scotland adopt a wide perspective on health, but most fail to identify
      differential impacts. Health involvement in scoping of health issues and better
      use of health evidence may enhance their quality.

PMID- 21855100
TI  - High prevalence of toxinogenic Clostridium difficile in Nigerian adult HIV
      patients.
AB  - Clostridium difficile is the most commonly identified bacterial cause of
      nosocomial and HIV-related diarrhea. In many developing countries, antibiotic
      access is unregulated. Nigeria has the third highest HIV burden worldwide. Due to
      perceptions of low prevalence and resource incapacity, patients with diarrhea are
      not tested for toxinogenic C. difficile infection (CDI). In this pilot study
      which included 97 HIV-positive patients at two hospitals in Nigeria, the
      estimated prevalence of CDI was 43% and 14% for in-patients and out-patients
      respectively. HIV-positive out-patients were more likely to have toxinogenic CDI
      than non-HIV out-patients (P=0.007, Fisher's exact test).

PMID- 21855101
TI  - Characteristics of children hospitalized with dengue fever in an outbreak in Rio
      de Janeiro, Brazil.
AB  - During a dengue epidemic in Rio de Janeiro in 2007-2008 the Instituto de
      Puericultura e Pediatria Martagao Gesteira Hospital was a reference for admitted
      children. The World Health Organization (WHO) considered several manifestations
      as warning signs of severe dengue This is a retrospective cohort study of all
      children admitted with dengue fever. Clinical variables considered warning signs
      by WHO were evaluated in the multivariate analysis, to investigate if they were
      independently associated with severe dengue. One hundred and eighty one children
      were admitted, aged from 4 months to 15 years; 30 were classified as severe
      dengue. Abdominal pain (OR=2.63, 95% CI 1.06-6.53) and lethargy (OR=3.40, 95% CI
      1.45-7.99) were independently associated with severe dengue.

PMID- 21855103
TI  - Occurrence and fate of TMDD in wastewater treatment plants in Germany.
AB  - The occurrence and fate of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) was
      investigated in four wastewater treatment plants (WWTPs) in Germany. The
      concentration of TMDD in influents and effluents in the WWTPs ranged from 134
      ng/L to 5846 ng/L and from <LOQ to 3539 ng/L correspondingly. Loads determined in
      influents (10.1 g/d-1142 g/d) and effluents (<LOQ--425 g/d) indicate that TMDD is
      partially removed from the wastewater. The elimination rates varied between 33%
      and 68%. Based on the load analysis, the TMDD effluent discharge of WWTPs
      investigated varied from 8.29 kg/a to 52.6 kg/a. Day and week profiles were
      recorded and indicated that TMDD is introduced into the sewage through household
      and indirect dischargers with high fluctuations. Seasonal variations in the TMDD
      loads were also analyzed in three of the studied WWTPs. One of the WWTPs
      demonstrated statistically higher TMDD loads during the warm period (164 g/d)
      than during the cold period (91.3 g/d), for the others WWTPs any differences
      could not be established. The input of TMDD during weekends and working days was
      also studied. The results did not show any significant trend of TMDD discharge
      into the WWTPs.

PMID- 21855102
TI  - Differential requirements for clathrin endocytic pathway components in cellular
      entry by Ebola and Marburg glycoprotein pseudovirions.
AB  - Clathrin-mediated endocytosis was previously implicated as one of the cellular
      pathways involved in filoviral glycoprotein mediated viral entry into target
      cells. Here we have further dissected the requirements for different components
      of this pathway in Ebola versus Marburg virus glycoprotein (GP) mediated viral
      infection. Although a number of these components were involved in both cases;
      Ebola GP-dependent viral entry specifically required the cargo recognition
      proteins Eps15 and DAB2 as well as the clathrin adaptor protein AP-2. In
      contrast, Marburg GP-mediated infection was independent of these three proteins
      and instead required beta-arrestin 1 (ARRB1). These findings have revealed an
      unexpected difference between the clathrin pathway requirements for Ebola GP
      versus Marburg GP pseudovirion infection. Anthrax toxin also uses a clathrin-,
      and ARRB1-dependent pathway for cellular entry, indicating that the mechanism
      used by Marburg GP pseudovirions may be more generally important for pathogen
      entry.

PMID- 21855105
TI  - Inhibition kinetics of certain enzymes in the nervous tissue of vector snail
      Lymnaea acuminata by active molluscicidal components of Sapindus mukorossi and
      Terminalia chebula.
AB  - Effect of active molluscicidal components of Sapindus mukorossi and Terminalia
      chebula on the acetylcholinesterase (AChE), acid and alkaline phosphatase
      (ACP/ALP) activity in the nervous tissue of freshwater snail Lymnaea acuminata
      were studied. In vivo and in vitro exposure of saponin (active component of S.
      mukorossi pericarp) and tannic acid (active component of T. chebula)
      significantly inhibited the AChE, ACP and ALP activity in the nervous tissue of
      L. acuminata. The inhibition kinetics of these enzymes indicate that saponin and
      tannic acid caused competitive and competitive-non-competitive inhibition of
      AChE, respectively. Saponin also caused competitive and competitive-non
      competitive inhibition of ACP and ALP, respectively, whereas tannic acid caused
      competitive-non-competitive inhibition of ACP and ALP. Thus the inhibition of
      AChE, ACP and ALP by saponin and tannic acid in the nervous tissue of L.
      acuminata may be the cause of molluscicidal activity of S. mukorossi and T.
      chebula.

PMID- 21855104
TI  - Representative measurement of two-dimensional reactive phosphate distributions
      and co-distributed iron(II) and sulfide in seagrass sediment porewaters.
AB  - The high degree of heterogeneity within sediments can make interpreting one
      dimensional measurements difficult. The recent development and use of in situ
      techniques that measure two-dimensional distributions of porewater solutes have
      facilitated investigation of the role of spatial heterogeneity in sediment
      biogeochemistry. A colourimetric diffusive equilibration in thin films method has
      been developed that allows two-dimensional, high-resolution measurement of
      reactive phosphate in sediment porewaters. A method detection limit of 0.22 MUM,
      an effective upper limit of ~1000 MUM and relative standard deviations typically
      below 5% were achieved. This method was evaluated by deployment in seagrass
      (Zostera capricorni) colonised sediments, as part of combined probes with similar
      colourimetric methods for sulfide and iron(II). The two-dimensional, high
      resolution distributions obtained provide a highly representative measurement of
      the co-distributions of porewater solutes, allowing heterogeneous features and
      biogeochemical processes to be observed and interpreted. Microniches of high
      phosphate concentration >100 MUM were observed throughout the distributions and
      were interpreted to be due to localised zones of rapid organic matter
      mineralisation, possibly using electron acceptors other than iron(III)
      oxyhydroxides (e.g. aerobic respiration) as often they did not correspond with
      microniches of higher Fe(II) concentration.

PMID- 21855107
TI  - Phosphorus sorption on marine carbonate sediment: phosphonate as model organic
      compounds.
AB  - Organophosphonate, characterized by the presence of a stable, covalent, carbon to
      phosphorus (C-P) bond, is a group of synthetic or biogenic organophosphorus
      compounds. The fate of these organic phosphorus compounds in the environment is
      not well studied. This study presents the first investigation on the sorption of
      phosphorus (P) in the presence of two model phosphonate compounds, 2
      aminothylphosphonoic acid (2-AEP) and phosphonoformic acid (PFA), on marine
      carbonate sediments. In contrast to other organic P compounds, no significant
      inorganic phosphate exchange was observed in seawater. P was found to adsorb on
      the sediment only in the presence of PFA, not 2-AEP. This indicated that sorption
      of P from phosphonate on marine sediment was compound specific. Compared with
      inorganic phosphate sorption on the same sediments, P sorption from organic
      phosphorus is much less in the marine environment. Further study is needed to
      understand the potential role of the organophosphonate compounds in
      biogeochemical cycle of phosphorus in the environment.

PMID- 21855108
TI  - Activated soil filters for removal of biocides from contaminated run-off and
      waste-waters.
AB  - Building facades can be equipped with biocides to prevent formation of algal,
      fungal and bacterial films. Thus run-off waters may contain these highly active
      compounds. In this study, the removal of several groups of biocides from
      contaminated waters by means of an activated soil filter was studied. A technical
      scale activated vertical soil filter (biofilter) with different layers (peat,
      sand and gravel), was planted with reed (Phragmites australis) and used to study
      the removal rates and fate of hydrophilic to moderate hydrophobic (log K(ow) 1.8
      4.4) biocides and biocide metabolites such as: Terbutryn, Cybutryn (Irgarol(r)
      1051), Descyclopropyl-Cybutryn (Cybutryn and Terbutryn metabolite), Isoproturon,
      Diuron, and its metabolite Diuron-desmonomethyl, Benzo-isothiazolinone, n-Octyl
      isothiazolinone, Dichloro-n-octylisothiazolinone and Iodocarbamate (Iodocarb).
      Three experiments were performed: the first one (36 d) under low flow conditions
      (61 L m(-2) d(-1)) reached removal rates between 82% and 100%. The second one was
      performed to study high flow conditions: During this experiment, water was added
      as a pulse to the filter system with a hydraulic load of 255 L m(-2) within 5 min
      (retention time <1 h). During this experiment the removal rates of the compounds
      decreased drastically. For five compounds (Cybutryn, Descyclopropyl-Cybutryn,
      Diuron, Isoproturon, and Iodocarb) the removal dropped temporarily below 60%,
      while it was always above 70% for the others (Terbutryn, Benzo-isothiazolinone, n
      Octyl-isothiazolinone, Dichloro-n-octylisothiazolinone). However, this removal is
      a considerable improvement compared to direct discharge into surface waters or
      infiltration into soil without appropriate removal. In the last experiment the
      removal efficiencies of the different layers were studied. Though the peat layer
      was responsible for most of the removal, the sand and gravel layers also
      contributed significantly for some compounds. All compounds are rather removed by
      degradation than by sorption.

PMID- 21855109
TI  - Expression of immunoglobulin G in esophageal squamous cell carcinomas and its
      association with tumor grade and Ki67.
AB  - We and other research groups have previously shown that various cancer types can
      express immunoglobulin G, but investigation on of immunoglobulin G expression in
      esophageal cancer, a highly malignant tumor, and its biological significance has
      been lacking. In this study, we examined immunoglobulin G protein and its
      messenger RNA, as well as the expressions of recombination-activating gene 1,
      recombination-activating gene 2, and activation-induced cytidine deaminase in 142
      cases of esophageal cancer tissues, and 2 esophageal cancer cell lines (Eca109,
      SHEEC). We also compared their expressions with tumor grade and a proliferation
      marker, Ki67. We used immunohistochemistry, immunofluorescence, in situ
      hybridization, laser microdissection coupled with reverse transcriptase
      polymerase chain reaction, and Western blot analysis. We detected transcripts of
      immunoglobulin G 1 heavy-chain constant region, immunoglobulin-kappa and lambda
      light chains, immunoglobulin G variable region, and recombination-activating
      genes 1 and 2 in both esophageal cancer tissues and cell lines, whereas
      activation-induced cytidine deaminase was not detected. No immunoglobulin G
      receptor subtypes were detected. Statistic analysis revealed that immunoglobulin
      G expression correlated well with tumor grades (P < .001) and with the
      proliferation marker Ki67 (P < .001). Our results indicate that human esophageal
      cancer cells are capable of synthesizing immunoglobulin G, which is likely
      involved in the growth and proliferation of this highly malignant cancer and
      might also be used as a prognostic indicator in esophageal squamous cell
      carcinomas.

PMID- 21855110
TI  - Molecular and immunohistochemical characterization of B-cell lymphoma-2-negative
      follicular lymphomas.
AB  - Aberrant expression of the antiapoptotic protein BCL (B-cell lymphoma)-2 in
      neoplastic germinal centers is one of the diagnostic hallmarks of follicular
      lymphoma. If BCL-2 cannot be detected by immunohistochemistry, the distinction
      between florid follicular hyperplasia and follicular lymphoma might become a
      diagnostic challenge. Most of those cases also lack the typical t(14;18), and the
      underlying pathophysiologic conditions of follicular lymphoma that lack BCL-2
      protein expression are largely unknown. Here, we collected 18 BCL-2-negative
      follicular lymphoma cases from 5 different institutions. After restaining, 9
      cases proved to be truly BCL-2 negative (6 follicular lymphoma grade 2, 2
      follicular lymphoma grade 3a, and 1 follicular lymphoma grade 3b). In 4
      additional cases, BCL-2 was very faint (all grade 2). Of the 9 BCL-2-negative
      follicular lymphoma cases, 2 were negative for CD10 (22%); all showed expression
      of BCL-6. Apoptotic level as determined by caspase 3 was the lowest in the BCL-2
      positive follicular lymphoma group (15 +/- 8 mm(2)), the highest in the
      normal/reactive group (n = 7, 60 +/- 12 mm(2)) and very similar in the BCL-2 low
      follicular lymphoma and BCL-2-negative follicular lymphoma groups (25 +/- 13 and
      33 +/- 19 mm(2), respectively), assuming an intermediate position between
      reactive follicles and BCL-2-positive neoplastic follicles (P < .001 [Kruskal
      Wallis]). Also noted was a difference in proliferation fractions between the BCL
      2-positive follicular lymphoma (27% +/- 15%), the BCL-2 low follicular lymphoma
      (30% +/- 20%) and the BCL-2-negative follicular lymphoma groups (30% +/- 22%).
      Regarding the network of follicular dendritic cells, 8 (89%) of 9 cases from the
      BCL-2-negative subgroup showed disrupted, weakly developed networks, whereas all
      of the follicular lymphoma BCL-2 low-expression cases showed a well-defined and
      strongly developed follicular dendritic cell network. Among BCL-2-negative
      follicular lymphoma, BCL-2 and BCL-6 breaks were found in 1 case each, whereas in
      the follicular lymphoma BCL-2 low group, only 1 case with a BCL-6 break was
      recorded. No statistically significant result was achieved upon assessment of BCL
      2alpha or BCL-2beta RNA or the ratio of alpha/beta isolated by real-time
      polymerase chain reaction. Taken together, BCL-2-negative follicular lymphoma did
      not show a BCL-2 break on the genetic level and showed both increased apoptotic
      and proliferation rates compared with BCL-2-positive follicular lymphoma. In our
      series, BCL-6 breaks were infrequent in BCL-2-negative follicular lymphoma.

PMID- 21855112
TI  - Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity
      pneumonitis.
AB  - Hypersensitivity pneumonitis is an inflammatory lung disease that develops in
      response to exposure to antigen. Cases can be stratified by the duration of
      exposure and speed of symptom progression into acute, subacute, and chronic
      hypersensitivity pneumonitis. Although the pathologic features of subacute
      hypersensitivity pneumonitis are well established and those of chronic
      hypersensitivity pneumonitis have been reported, little is known about the
      histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic
      features of 5 patients with clinically confirmed hypersensitivity pneumonitis and
      rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity
      pneumonitis with symptom exacerbation. Histopathologic features assessed in each
      case included those characteristic of subacute hypersensitivity pneumonitis
      (bronchiolocentric chronic inflammation, histiocytic aggregates, and
      bronchiolitis obliterans), those associated with acute inflammation (fibrin
      deposition and neutrophilic infiltrate), and fibrosis. The classic features of
      hypersensitivity pneumonitis were identified in all 8 cases, with 1 also
      exhibiting fixed fibrosis confirming underlying chronic hypersensitivity
      pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent
      was significant (28% surface area fibrin deposition/total disease area on
      average). Two had intra-alveolar fibrin so marked that it resembled acute
      fibrinous and organizing pneumonia. In addition, prominent interstitial
      neutrophilic infiltrate (>=5 cells/high-power field) was seen in all cases. These
      features have not been reported as characteristics of subacute or chronic
      hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic
      infiltrate may characterize acute hypersensitivity pneumonitis or abrupt
      exacerbation of hypersensitivity pneumonitis, and these along with characteristic
      features of subacute hypersensitivity pneumonitis (granulomatous inflammation and
      bronchiolocentricity) are sufficient to establish a morphologic diagnosis,
      particularly in conjunction with clinicoradiologic features.

PMID- 21855111
TI  - Expression of the Ets transcription factor EHF in serous ovarian carcinoma
      effusions is a marker of poor survival.
AB  - The EHF (Ets homologous factor) gene was previously shown to be overexpressed in
      ovarian/primary peritoneal serous carcinoma compared to malignant mesothelioma
      using gene expression arrays. The objective of this study was to validate this
      finding at the mRNA level in a larger series. We analyzed the diagnostic role of
      EHF in 98 ovarian serous carcinoma effusions, 23 malignant mesothelioma specimens
      (20 effusions, 3 surgical specimens), and 28 primary ovarian serous carcinomas
      using quantitative real-time polymerase chain reaction. Expression levels of EHF
      in ovarian carcinoma were additionally investigated for association with
      clinicopathologic parameters and survival. Quantitative real-time polymerase
      chain reaction analysis showed significantly higher expression of EHF mRNA in
      ovarian carcinoma effusions and in primary ovarian carcinoma compared to
      malignant mesothelioma effusions (P < .001 for both). EHF mRNA expression was
      additionally higher in primary ovarian carcinomas compared to effusions of this
      cancer (P < .001). In univariate analysis for all patients with effusions, higher
      EHF mRNA levels were associated with a trend for shorter progression-free
      survival (P = .066), which became significant in analysis of 45 patients with
      primary diagnosis pre-chemotherapy effusions (P = .01). In Cox multivariate
      analysis, EHF mRNA expression was an independent predictor of poor progression
      free survival for all patients and patients with primary diagnosis pre
      chemotherapy effusions (P = .033 and P = .009, respectively). EHF mRNA levels
      differentiate ovarian carcinoma from malignant mesothelioma and may thus be of
      diagnostic value in this setting. EHF may be a novel prognostic marker in ovarian
      carcinoma.

PMID- 21855113
TI  - SCARA3 mRNA is overexpressed in ovarian carcinoma compared with breast carcinoma
      effusions.
AB  - Scavenger receptor class A, member 3 (SCARA3) was previously found to be
      overexpressed in ovarian/primary peritoneal carcinoma (OC/PPC) compared with
      breast carcinoma effusions by global gene expression analysis. The present study
      aimed to validate this finding applying quantitative PCR and analyzing the
      association between SCARA3 expression and clinicopathologic parameters in a large
      OC cohort. SCARA3 messenger RNA (mRNA) expression was analyzed in 127 effusions
      (103 ovarian/peritoneal/fallopian tube carcinomas, 9 breast carcinomas, 15
      malignant mesotheliomas [MM]), and 30 solid primary OCs. The association between
      OC SCARA3 levels and clinicopathologic parameters was investigated. SCARA3 mRNA
      was expressed in all effusions, irrespective of tumor type. However, transcript
      levels were significantly higher in OC compared with breast carcinoma (P < .001)
      and MM (P = .011) effusions. Primary OCs and effusions had comparable expression
      levels. Higher SCARA3 expression was found in disease recurrence postchemotherapy
      compared with primary diagnosis prechemotherapy OC effusions (P = .001), and this
      difference was significant for treatment with both platinum agents (P = .006) and
      paclitaxel (P = .002). SCARA3 levels in effusions and primary carcinomas were
      unrelated to patient age, tumor grade, FIGO stage, residual tumor volume after
      surgery, response to chemotherapy, or survival (P > .05 for all). In conclusion,
      SCARA3 mRNA by quantitative PCR is highly expressed in OC and may aid in
      differentiating this tumor from other cancers, particularly breast carcinoma, in
      effusions. The consistently high SCARA3 levels in both primary carcinomas and
      metastatic cells in effusions, and its up-regulation along disease progression
      from diagnosis to recurrence, suggest a role in ovarian cancer biology.

PMID- 21855114
TI  - Comprehensive analysis of HER2 expression and gene amplification in gastric
      cancers using immunohistochemistry and in situ hybridization: which scoring
      system should we use?
AB  - It has been reported that HER2 expression is different in gastric and breast
      cancers, and a gastric cancer scoring system (GCSS) has recently been suggested.
      We investigated HER2 protein expression using GCSS and a breast cancer scoring
      system (BCSS) and correlated it with HER2 gene amplification. HER2 status was
      evaluated in 1091 cases by analyzing tissue microarrays constructed using 2
      different cores from each case. Polyclonal (HercepTest) and monoclonal (Pathway)
      antibodies were used for immunohistochemistry (IHC), and results were scored by
      BCSS and GCSS. Gene amplification was evaluated by automated dual-color silver
      enhanced in situ hybridization (SISH) in all cases and correlated with the
      results from fluorescence in situ hybridization (FISH) in 590 cases. The
      concordance between the IHC results using polyclonal and monoclonal antibodies
      was high (kappa = 0.785). The results of dual-color SISH and FISH showed very
      high concordance as well (kappa = 0.918). GCSS was significantly more sensitive
      for detecting SISH positivity than was BCSS in both antibodies (polyclonal, P =
      .003; monoclonal, P < .001), but specificity was higher in BCSS than GCSS
      (polyclonal, P = .004; monoclonal, P < .001). It has been recently shown that
      HER2-overexpressing patients with unresectable gastric cancer benefited from
      trastuzumab therapy. Because IHC is recommended before gene amplification studies
      in HER2 testing, GCSS should be used for evaluating HER2 expression in gastric
      cancers.

PMID- 21855115
TI  - Where are inion and endinion? Variations of the exo- and endocranial morphology
      of the occipital bone during hominin evolution.
AB  - The occipital bone is frequently investigated in paleoanthropological studies
      because it has several features that help to differentiate various fossil hominin
      species. Among these features is the separation between inion and endinion, which
      has been proposed to be an autapomorphic trait in (Asian) Homo erectus.
      Methodologies are developed here to quantify for the first time the location of
      these anatomical points, and to interpret their variation due to the complex
      interactions between exocranial and endocranial size and shape of the occipital
      and nuchal planes, as well as the occipital lobes and cerebellum. On the basis of
      our analysis, neither 'the separation between inion and endinion' nor 'endinion
      below inion' can be considered as an autapomorphic trait in H. erectus, since
      this feature is a condition shared by extant African great apes and fossil
      hominins. Moreover, our results show that the exo- and endocranial anatomy of the
      occipital bone differs between hominins (except Paranthropus boisei specimens and
      KNM-ER 1805) and great apes. For example, chimpanzees and bonobos are
      characterized by a very high position of inion and their occipital bone shows an
      antero-posterior compression. However, these features are partly correlated with
      their small size when compared with hominins. Asian H. erectus specimens have a
      thick occipital torus, but do not differ from other robust specimens, neither in
      this feature nor in the analysed exo- and endocranial proportions of the
      occipital bone. Finally, the apparent brain size reduction during the Late
      Pleistocene and variation between the sexes in anatomically modern humans (AMH)
      reflect that specimens with smaller brains have a relatively larger posterior
      height of the cerebellum. However, this trend is not the sole explanation for the
      'vertical shift' of endinion above inion that appears occasionally and
      exclusively in AMH.

PMID- 21855116
TI  - Immunohistochemical studies on the poll gland of the dromedary camel (Camelus
      dromedarius) during the rutting season.
AB  - The poll glands are subcutaneous exocrine glands located on the back of the neck
      behind the ears in male camels. The function of poll glands is not well known,
      though they are thought to play a role during the rutting season. The presence,
      location and degree of immunolocalization of microfilaments and intermediate
      filament systems: actin and cytokeratins (Cks) and also S100 protein were studied
      in the poll glands in sexually mature one-humped camels during the rutting
      season. These proteins were variably expressed between the epithelia,
      perialveolar, interalveolar tissue and the periductal tissue. Strong alpha-smooth
      muscle actin (alpha-SMA) immunoreactivity (IR) was displayed by the perialveolar
      myoepithelial cells, periductal and vascular smooth muscle cells (SMCs), but not
      in the epithelial cells. Cytokeratin (Ck)-IR was strong in the epithelial lining
      of the secretory alveoli and excretory ducts, however, the apical blebs of the
      secretory cells were almost negative. Weak to moderate Ck-IR was observed in the
      perialveolar myoepithelial cells, but not in the interalveolar tissue or
      endothelial cells. S100 protein was expressed variably in the epithelial lining
      of the secretory alveoli. S100-IR was more obvious in the supranuclear region and
      the apical blebs. Variable reaction was observed in the perialveolar
      myoepithelial cells, periductal and interductal tissue and endothelial cells.

PMID- 21855117
TI  - Co-expression of hepatocyte growth factor and c-met in epithelial odontogenic
      tumors.
AB  - Hepatocyte growth factor (HGF) and its receptor, c-met, have been shown to
      regulate cell proliferation, motility and morphology in a variety of cell types.
      A significant role of the HGF/c-met pathway has been demonstrated in various
      tumors, however, little is known about the role of HGF/c-met pathway in
      odontogenic tumors. The aim of this study was to characterize the expression of
      HGF and c-met in 30 ameloblastomas, 7 unicystic ameloblastomas (luminal type), 10
      calcifying cystic odontogenic tumors, 10 adenomatoid odontogenic tumors (AOTs),
      30 keratocytic odontogenic tumors (KCOTs) and 6 ameloblastic carcinomas using an
      immunohistochemical method. HGF and c-met were generally immunolocalized in the
      cytoplasm of all epithelial tumor cells, except for keratinizing cells in
      acanthomatous ameloblastoma, in all the examined odontogenic tumors. These
      results, together with the expression of these two proteins in the epithelium of
      tooth germs, suggest that the HGF/c-met pathway is involved in the
      differentiation of odontogenic tumors. This pathway may also promote tumor
      proliferation in odontogenic tumors due to its potent mitogenic effect. The
      consistent and strong immunolocalization of HGF and c-met in squamous cells
      present in acanthomatous ameloblastomas, AOTs and ameloblastic carcinomas, and in
      the linings of KCOTs suggests that the HGF/c-met interaction may have an
      influence on squamous differentiation in these odontogenic tumors.

PMID- 21855118
TI  - Topotecan in patients with BRCA-associated and sporadic platinum-resistant
      ovarian, fallopian tube, and primary peritoneal cancers.
AB  - OBJECTIVE: To evaluate the efficacy of topoisomerase I inhibitor, topotecan, in
      patients with recurrent BRCA+ versus BRCA- ovarian, fallopian tube, and primary
      peritoneal carcinomas. METHODS: A single-institution retrospective analysis of
      platinum-resistant patients characterized for the presence or absence of known
      deleterious BRCA mutations. Patients received topotecan at a dose and schedule
      determined by their treating physician (five day or weekly). Response rate and
      progression-free survival (PFS) were assessed. RESULTS: A total of 50 patients (9
      BRCA+, 41 BRCA-) were treated with topotecan. Both groups were well balanced in
      terms of age, stage, grade, and number of prior therapies. All patients had high
      grade serous carcinoma. The clinical benefit rate in BRCA+ and BRCA- patients was
      0% and 26.8% (6 PRs, 6 SDs), respectively (p=0.18). Median PFS in BRCA+ and BRCA-
      pts was 1.7 months (95% CI: 1.0-2.8 months) and 2.5 months (95%CI: 1.9-2.8
      months), respectively (p=0.057). Median time to best response was 1.9 months, and
      median response duration 2.6 months. CONCLUSIONS: This analysis in a heavily
      pretreated cohort of patients fails to support the superiority of topotecan in
      BRCA+ platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers.
      Further study of this class of agents, specifically in less heavily-pretreated
      patients, may still be warranted.

PMID- 21855119
TI  - Temporal trends in the relative survival among patients diagnosed with ovarian
      cancer in Canada 1992-2005: a population-based study.
AB  - OBJECTIVE: Ovarian cancer affects about 2600 women annually in Canada and about
      1750 are expected to die from this disease. We estimated the trends in the
      relative survival ratio for patients diagnosed with epithelial invasive ovarian
      cancer in Canadian population between 1992 and 2005. METHODS: A flexible
      parametric model was used to estimate the relative survival ratio. Relative
      survival ratio is defined as the observed survival among cancer patients divided
      by the expected survival in the general population. We incorporated age group,
      histology of tumour, and region of patient residence at the time of diagnosis
      into a model to predict two- and five-year relative survival ratios based on the
      year of diagnosis where the effect of each variable was adjusted for the effects
      of the other variables. A restricted cubic splines with five knots was used to
      include year of diagnosis in the model. RESULTS: In total 7771 patients diagnosed
      with epithelial invasive ovarian cancer were included in this analysis with the
      mean age of 59.6 (SD=13.5) years at the time of diagnosis. About 75% of the
      patients were 50 years and older at the time of diagnosis and relative survival
      ratio substantially decreased with age. The tumour type was serous for 43% of
      cases followed by endometrioid (30.5%), clear cell (14.5%), mucinous (9.5%), and
      transitional cell (2.5%). The same pattern was observed for all regions although
      with some variation in the proportions. The worst survival observed for serous
      tumours. About 50% of the cases were diagnosed in Ontario. CONCLUSIONS: This is
      the first report that compares relative survival ratio for epithelial invasive
      ovarian cancer among geographic regions of Canada where a higher relative
      survival ratio was observed in Ontario compared to the other regions. The
      relative survival decreased with age and showed geographic variation. The work
      indicates that advances in management of women with ovarian cancer have improved
      two- and five-year relative survival ratios.

PMID- 21855121
TI  - "A bad wound may heal, but a bad name can kill"--lessons learned from "hyper-IgM
      syndrome".

PMID- 21855120
TI  - Therapy-related myeloid leukemia after treatment for epithelial ovarian
      carcinoma: an epidemiological analysis.
AB  - OBJECTIVE: Therapy related acute myeloid leukemia (t-AML) is a potential late
      complication of cytotoxic therapy, and it is of particular concern in the
      treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple
      courses of chemotherapy during the course of their disease. This study examines
      the incidence, characteristics and clinical outcomes of patients who developed
      secondary myeloid-type leukemia after a diagnosis of EOC. METHODS: National
      Cancer Institute's Surveillance, Epidemiology and End Results database was pooled
      for diagnosis of secondary myeloid leukemia after an initial diagnosis of EOC.
      This group of patients was compared to patients with de novo AML, and to EOC
      patients who did not develop secondary myeloid leukemia. Demographic,
      cytopathological and survival data were recorded. Cox Proportional Hazards model
      was used to calculate hazard ratios (HR) for developing secondary leukemia and to
      determine the statistically significant variables impacting survival. Kaplan
      Meier estimates of survival were obtained and comparisons between the groups were
      performed using log-rank test. RESULTS: One hundred and nine myeloid leukemia
      cases were identified among 63,359 patients with a prior diagnosis of EOC for an
      overall incidence of 0.17%. The median latency to development of leukemia was 4
      years (range 0-27 years). Median survival from the time of secondary leukemia
      diagnosis was 3 months and significantly worse than the 6 month median survival
      in patients with de novo AML (p<0.001). Age at leukemia diagnosis greater than 65
      and development of secondary vs. de novo leukemia had a statistically worse
      prognosis on multivariate analysis (HR of 2.69, 95%CI 2.60-2.78 and 1.81, 95%CI
      1.49-2.20 respectively). The development of secondary leukemia was more common
      with EOC diagnosis made prior to the platinum/taxane era (HR 6.70, 95%CI 3.69
      12.18). There was no difference in median survival between EOC patients who
      developed AML and those who did not. CONCLUSION: Development of t-AML is a rare
      but lethal event among EOC patients, and its incidence has decreased
      significantly since the use of platinum/taxane-based chemotherapy became the
      standard of care.

PMID- 21855123
TI  - Cesarean delivery, antibiotic exposure, and probiotics: relationship with
      childhood asthma.

PMID- 21855125
TI  - Approaches to stepping up and stepping down care in asthmatic patients.
AB  - The variability in symptom control is a challenging feature of asthma that
      necessitates careful monitoring and the need to step up and step down
      individualized therapeutic regimens over time. This stepwise concept in asthma
      therapy can be considered in at least 3 contexts. For lack of control that is
      persistent over long periods of time, an increase in the overall medication or a
      step-up long-term strategy is indicated. A second approach, the step-up short
      term strategy, can be used during a temporary loss of acceptable control, such as
      at the onset of a viral respiratory tract illness. In these cases a step-up in
      therapy is usually terminated in 3 to 10 days once asthma control has been
      satisfactorily achieved. Finally, for treating symptoms related to the
      variability of asthma on a day-to-day basis, inhaled corticosteroids used
      concomitantly with a beta-agonist have been evaluated, although this treatment is
      not currently approved in the United States. We will term this particular
      intervention a step-up intermittent strategy. Here we summarize the existing data
      regarding these 3 approaches to step up care and step down management, as well as
      to identify areas where more comparative studies are necessary to provide further
      guidance to clinicians regarding proper step-up and step-down strategies in the
      care of asthma.

PMID- 21855128
TI  - The role of depressive symptoms, family invalidation and behavioral impulsivity
      in the occurrence and repetition of non-suicidal self-injury in Chinese
      adolescents: a 2-year follow-up study.
AB  - This study used zero-inflated poisson regression analysis to examine the role of
      depressive symptoms, family invalidation, and behavioral impulsivity in the
      occurrence and repetition of non-suicidal self-injury among Chinese community
      adolescents over a 2-year period. Participants, 4782 high school students, were
      assessed twice during the follow-up period. Results indicate that while Year 1
      depressive symptoms and family invalidation were significantly associated with
      the occurrence of Year 2 NSSI, Year 1 behavioral impulsivity contributed to both
      the occurrence and repetition of Year 2 NSSI. Findings of this study suggest that
      adolescents who display multiple impulsive behaviors may be at particular risk
      for engaging in repetitive NSSI. Clinical implications of these findings and
      future research directions were discussed.

PMID- 21855127
TI  - Individual IL-3 priming is crucial for consistent in vitro activation of donor
      basophils in patients with chronic urticaria.
AB  - BACKGROUND: The in vivo autologous serum skin test (ASST) is the diagnostic gold
      standard to detect autoantibodies against FcepsilonRI or IgE itself, as well as
      other autoreactive serum components, in patients with chronic spontaneous
      urticaria (CU). Coincubation of patient sera with donor basophils and measuring
      their degranulation in vitro could be a safe alternative but has shown
      inconsistent results. OBJECTIVE: Optimization of the basophil activation test to
      detect autoreactive serum components in patients with CU. METHODS: The ability of
      patient sera to induce CD63 and CD203c in donor basophils (n = 15) was measured
      by means of flow cytometry. Sera of 20 patients with CU (10 with positive ASST
      results), 15 patients with cold urticaria, and 27 healthy control subjects were
      included to optimize test conditions with donor basophils and a basophil cell
      line (RBL703/21) followed by testing of 110 consecutive patients from clinical
      routine. RESULTS: We demonstrate that individual IL-3 priming normalized the
      initially inconsistent basophil reactivity and led to reproducible and comparable
      test results irrespective of the basophil donors used. CD203c as an activation
      marker and the use of a basophil cell line were less suitable for this purpose.
      CONCLUSION: The basophil activation test with individualized IL-3 priming for
      each basophil donor is a reproducible and reliable alternative to the ASST. There
      are several advantages over the ASST: no risk of accidental infection, no
      influence of antihistamines on the test result, quantifiable results, and a
      potential in providing treatment monitoring. The exact nature of the
      degranulating factor or factors in patient sera remains an open question.

PMID- 21855129
TI  - Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct
      based bone tissue engineering.
AB  - Bone tissue engineering (BTE) has been demonstrated an effective approach to
      generate bone tissue and repair bone defect in ectopic and orthotopic sites. The
      strategy of using a prevascularized tissue-engineered bone grafts (TEBG)
      fabricated ectopically to repair bone defects, which is called live bone graft
      surgery, has not been reported. And the quantitative advantages of
      vascularization and osteogenic environment in promoting engineered bone formation
      have not been defined yet. In the current study we generated a tissue engineered
      bone flap with a vascular pedicle of saphenous arteriovenous in which an
      organized vascular network was observed after 4 weeks implantation, and followed
      by a successful repaire of fibular defect in beagle dogs. Besides, after a 9
      months long term observation of engineered bone formation in ectopic and
      orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated
      by CT (computed tomography) analysis. By the comparison of bone formation and
      scaffold degradation between different groups, the influences of vascularization
      and micro-environment on tissue engineered bone were quantitatively analyzed. The
      results showed that in the first 3 months vascularization improved engineered
      bone formation by 2 times of non-vascular group and bone defect micro-environment
      improved it by 3 times of ectopic group, and the CHA-scaffold degradation was
      accelerated as well.

PMID- 21855131
TI  - Inflammatory responses to pulmonary application of PEI-based siRNA nanocarriers
      in mice.
AB  - Polymeric non-viral vector systems for pulmonary application of siRNA are
      promising carriers, but have failed to enter clinical trials because of safety
      and efficiency problems. Therefore, improving their transfection efficiency, as
      well as their toxicological profile, is the subject of intensive research
      efforts. Six different poly(ethylene imine) (PEI)-based nanocarriers, with
      hydrophilic and hydrophobic PEG modifications, were toxicologically evaluated for
      pulmonary application in mice. Nanocarriers were intratracheally instilled to
      determine their toxicological profile, with particular focus on the inflammatory
      response in the lungs. Nanocarriers from both groups caused an acute inflammatory
      response in the lungs, albeit with different resolution kinetics and
      cytotoxicity. Hydrophobic modifications caused a severe inflammatory response
      with increased epithelial barrier permeability, accompanied by an acute
      antioxidant response. Hydrophilic modifications, with high PEG-grafting degrees,
      induced less proinflammatory effects without depleting macrophages and disrupting
      the epithelial/endothelial barrier in the lungs, while showing only a minor
      oxidative stress response. For pulmonary applications, local proinflammatory
      effects should be optimized by further development of nanocarriers with highly
      grafted PEG-PEI-based carriers or Jeffamine-modified hydrophobic PEI
      modifications.

PMID- 21855132
TI  - In vitro enzymatic degradation of poly (glycerol sebacate)-based materials.
AB  - Enzymatic degradation is a major feature of polyester implants in vivo. An in
      vitro experimental protocol that can simulate and predict the in vivo enzymatic
      degradation kinetics of implants is of importance not only to our understanding
      of the scientific issue, but also to the well-being of animals. In this study, we
      explored the enzymatic degradation of PGS-based materials in vitro, in tissue
      culture medium or a buffer solution at the pH optima and under static or cyclic
      mechanical-loading conditions, in the presence of defined concentrations of an
      esterase. Surprisingly, it was found that the in vitro enzymatic degradation
      rates of the PGS-based materials were higher in the tissue culture medium than in
      the buffered solution at the optimum pH 8. The in vitro enzymatic degradation
      rate of PGS-based biomaterials crosslinked at 125 degrees C for 2 days was
      approximately 0.6-0.9 mm/month in tissue culture medium, which falls within the
      range of in vivo degradation rates (0.2-1.5mm/month) of PGS crosslinked at
      similar conditions. Enzymatic degradation was also further enhanced in relation
      to mechanical deformation. Hence, in vitro enzymatic degradation of PGS materials
      conducted in tissue culture medium under appropriate enzymatic conditions can
      quantitatively capture the features of in vivo degradation of PGS-based materials
      and can be used to indicate effective strategies for tuning the degradation rates
      of this material system prior to animal model testing.

PMID- 21855130
TI  - PEGylated TNF-related apoptosis-inducing ligand (TRAIL) for effective tumor
      combination therapy.
AB  - Although PEGylated TNF-related apoptosis-inducing ligand (PEG-TRAIL) has good
      tumor cell specificity and stability, its therapeutic potential is restricted by
      the development of tumor cell resistance. The purpose of this study was to
      develop an effective combination therapy with sustained biological activity based
      on microspheres. Doxorubicin (DOX), PEG-TRAIL, and DOX plus PEG-TRAIL (dual
      agent) were microencapsulated into poly (lactic-co-glycolic acid) (PLGA)
      microspheres using a double-emulsion solvent extraction method. Prepared dual
      agent microspheres showed the encapsulation efficiency 69.4 +/- 2.3 for DOX and
      87.7 +/- 2.9% for PEG-TRAIL. Potential anti-tumor efficacy of this system was
      investigated in vitro and in vivo in a human colon cancer (HCT116) and in a human
      prostate cancer (PC-3). DOX and PEG-TRAIL release from dual agent microspheres
      were biologically active and significantly inhibited the TRAIL-sensitive HCT116
      and resistant PC-3 cells in vitro. Dual agent microspheres simultaneous delivery
      of DOX and PEG-TRAIL was superior to all other DOX or PEG-TRAIL microspheres in
      vivo. A single local injection of PLGA microspheres loaded with low amounts of
      DOX, PEG-TRAIL, or dual agent resulted in 14.8, 30.2, and 63.6% reductions in
      HCT116 tumor volume and 20.4, 14.2, and 67.7% reductions in PC-3 tumor volume at
      35 days. Our findings show that dual agent microspheres offer a promising means
      of delivering DOX and PEG-TRAIL to tumor sites.

PMID- 21855133
TI  - An integrated sensing system for detection of DNA using new parallel-motif DNA
      triplex system and graphene--mesoporous silica--gold nanoparticle hybrids.
AB  - In this article, we demonstrate the use of graphene--mesoporous silica--gold NP
      hybrids (GSGHs) as an enhanced element of the integrated sensing platform for the
      ultra-sensitive and selective detection of DNA by using strand-displacement DNA
      polymerization and parallel-motif DNA triplex system as dual amplifications. We
      find that the present new sensing strategy based on GSGHs is able to detect
      target DNA with a fairly high detection sensitivity of 10 fm through the
      hybridization of duplex DNA to the acceptor DNA for the formation of parallel
      motif DNA triplex on the multilayer film (containing GSGHs and redox probe)
      modified functional interface, and even has a good capability to investigate the
      single nucleotide polymorphisms (SNPs). The detection limit for target DNA is
      about two orders of magnitude lower than that of graphene-based DNA
      electrochemical impedance spectroscopy (EIS) sensor (6.6 pm), four orders of
      magnitude lower than those of graphene-based DNA sensors coupled with fluorescent
      assay (100 pm and 1 nm) and five orders of magnitude lower than those of field
      effect transistor (FET)-based assays (1 nm and 2 nm). Most importantly, our
      present sensing system can also be facilely achieved in the ITO electrode array,
      which is of paramount importance for possible multiplex analysis in lab-on-chip.

PMID- 21855126
TI  - Most nocturnal asthma symptoms occur outside of exacerbations and associate with
      morbidity.
AB  - BACKGROUND: Although nocturnal awakenings help categorize asthma severity and
      control, their clinical significance has not been thoroughly studied. OBJECTIVE:
      We sought to determine the clinical consequences of nocturnal asthma symptoms
      requiring albuterol (NASRAs) in children with mild-to-moderate persistent asthma
      outside of periods when oral corticosteroids were used for worsening asthma
      symptoms. METHODS: Two hundred eighty-five children aged 6 to 14 years with mild
      to-moderate persistent asthma were randomized to receive one of 3 controller
      regimens and completed daily symptom diaries for 48 weeks. Diary responses were
      analyzed for the frequency and consequences of NASRAs. RESULTS: NASRAs occurred
      in 72.2% of participants at least once, and in 24.3% of participants, they
      occurred 13 or more times. The majority (81.3%) of nocturnal symptoms occurred
      outside of exacerbation periods and were associated the next day with the
      following events: albuterol use (56.9% of days preceded by nocturnal symptoms vs
      18.1% of days not preceded by nocturnal symptoms; relative risk [RR], 2.3; 95%
      CI, 2.2-2.4), school absence (5.0% vs 0.3%; RR, 10.6; 95% CI, 7.8-14.4), and
      doctor contact (3.7% vs 0.2%; RR, 8.8; 95% CI, 6.1-12.5). Similar findings were
      noted during exacerbation periods (RRs of 1.7 for albuterol use, 5.5 for school
      absence, and 4.9 for doctor contacts). Nocturnal symptoms did not predict the
      onset of exacerbations. CONCLUSION: Nocturnal symptoms requiring albuterol in
      children with mild-to-moderate persistent asthma receiving controller therapy
      occurred predominantly outside of exacerbation periods. Despite being poor
      predictors of exacerbations, they were associated with increases in albuterol
      use, school absences, and doctor contacts the day after nocturnal symptom
      occurrences.

PMID- 21855134
TI  - Triazacryptand-based fluorescent sensors for extracellular and intracellular K+
      sensing.
AB  - A 4-amino-naphthalimide derived fluorophore with a triazacryptand moiety ligand
      was synthesized as a potassium ion (K(+)) sensor (KS1). This sensor is a monomer
      possessing a polymerizable vinyl group. By taking advantage of the polymerizable
      characteristics of the vinyl group, KS1 was polymerized with 2-hydroxyethyl
      methacrylate (HEMA) and acrylamide (AM) to form K(+) sensing films for
      extracellular sensing. The sensitivity of the films to potassium ions can be
      further tuned through the adjustment of the HEMA and AM weight ratios as well as
      introduction of positive or negative charge-containing segments. KS1 and its
      poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (PHEMA-co-PAM) thin films
      show high selectivity for K(+) over competing sodium ions (Na(+)) at
      physiological concentrations. Extracellular sensing was demonstrated using a KS1
      conjugated PHEMA-co-PAM thin film to measure the K(+) efflux of Escherichia coli
      (E. coli) and Bacillus subtilis (B. subtilis) stimulated by lysozyme. Meanwhile,
      KS1 itself permeates human glioblastoma U87MG and human esophagus premalignant CP
      A cell lines. KS1 was used to monitor K(+) efflux stimulated by adenosine-5'
      triphosphate (ATP), amphotericin, and a mixture of nigericin, bumetanide and
      ouabain, demonstrating application of this material as an intracellular potassium
      ion sensor.

PMID- 21855136
TI  - Trophoblast deportation part I: review of the evidence demonstrating trophoblast
      shedding and deportation during human pregnancy.
AB  - Trophoblast deportation was first described before the turn of the 20th Century
      by the German Scientist Schmorl and is now considered a normal physiological
      process during human pregnancy. Increased shedding and deportation of placental
      trophoblast is well documented in preeclampsia, one of the most common diseases
      of pregnancy. This review summarises the seminal historical and contemporary
      publications that have contributed to our knowledge of trophoblast deportation to
      the maternal lungs, their presence and quantity in the maternal circulation
      during normal pregnancy and during preeclampsia, and the range of morphologies
      deported trophoblasts display. Finally, the contentious nature of the deported
      multinucleated trophoblasts' current nomenclature (syncytial knots vs. sprouts)
      is considered.

PMID- 21855135
TI  - Bovine fetal DNA in the maternal circulation: Applications and implications.
AB  - OBJECTIVE: The main aim of the present study was to detect bovine fetal DNA in
      the maternal circulation, a relatively unexplored subject in the literature.
      STUDY DESIGN: DNA was extracted from blood of 84 primipara cows (Bos indicus) at
      different gestational ages (30-270 days) and from 100 adult animals (50 males and
      50 non-pregnant cows). The samples were analyzed using PCR with primers for TSPY
      gene. RESULTS: Molecular results matched the fetal phenotypic gender in all 47
      male and 37 female fetuses, including early pregnancy, and in control animals.
      CONCLUSIONS: These results evidence a bovine transplacental fetal DNA passage.

PMID- 21855137
TI  - Regional variation in angiotensin converting enzyme activity in the human
      placenta.
AB  - Sensitivity of chorionic plate arteries to angiotensin II (AngII) is greatest at
      the placental periphery. Angiotensin converting enzyme (ACE) is central to the
      synthesis of AngII and is present in the placental vasculature. We measured
      vascular ACE activity/mg protein at 8-9 sites between the cord insertion and the
      periphery in 12 term placentae from normotensive, vaginally-delivered women. ACE
      increased from insertion to the periphery (P = 0.015); median ACE for each
      placenta was positively correlated with placental weight (P < 0.05) and
      placental:birthweight ratio (P < 0.02). We speculate that this may be related to
      fetal programming since placental:birthweight ratio is related to long-term
      health.

PMID- 21855138
TI  - CART peptide stimulation of G protein-mediated signaling in differentiated PC12
      cells: identification of PACAP 6-38 as a CART receptor antagonist.
AB  - CART peptides are peptide neurotransmitters and hormones that are involved in
      many different physiological responses. While much is known about the peptides
      regarding their structure, processing and gene regulation, less is known about
      their postsynaptic actions and receptors. Using (125)I-CART 61-102 as a ligand
      and unlabeled CART 61-102 or CART 55-102 as displacers, high-affinity specific
      binding was detected in PC12 cells. Differentiation of the PC12 cells increased
      specific binding several-fold. The increase in specific binding found after
      differentiation was inhibited by actinomycin D and cycloheximide, suggesting that
      the increase in specific binding was dependent on RNA and protein synthesis. CART
      1-27, a peptide that has never been shown to elicit responses, did not displace
      (125)I-CART 61-102 binding, nor did more than 20 other peptides that were
      examined. Surprisingly, however, PACAP 1-38 and PACAP 6-38 were found to be low
      affinity inhibitors of CART binding. CART treatment increased binding of (35)S
      GTPgamma-S to PC12 cell membranes. Moreover, CART treatment of intact PC12 cells
      elicited robust increases in phospho-ERK in a manner that was increased with
      differentiation, blocked by pertussis toxin and antagonized by PACAP 6-38. These
      findings extend previous research and suggest that the CART binding site in PC12
      cells reflects a G protein-coupled receptor linked with Gi/o, and also
      demonstrate that PACAP 6-38 may be useful as a CART receptor antagonist.

PMID- 21855139
TI  - Determination of specific neuropeptides modulation time course in a rat model of
      osteoarthritis pain by liquid chromatography ion trap mass spectrometry.
AB  - Animal models are useful to evaluate pharmacological therapies to alleviate joint
      pain. The present study characterized central neuropeptides modulation in the
      monoiodoacetate (MIA) rat model. Animals receiving a single 3mg MIA injection
      were euthanized at 3, 7, 14, 21 and 28 days post injection. Spinal cords were
      analyzed by liquid chromatography ion trap mass spectrometry. Up-regulations of
      the calcitonin gene-related peptide and substance P were observed starting on
      days 7 and 28 respectively, whereas big dynorphin(1-32) content decreased
      significantly on day 14 in comparison to control animals (P<0.05). Preclinical
      drug evaluations using this model should be conducted between 7 and 21 days post
      injection when the lesions resemble most to human osteoarthritis.

PMID- 21855140
TI  - Trauma-focused CBT for youth who experience ongoing traumas.
AB  - Many youth experience ongoing trauma exposure, such as domestic or community
      violence. Clinicians often ask whether evidence-based treatments containing
      exposure components to reduce learned fear responses to historical trauma are
      appropriate for these youth. Essentially the question is, if youth are
      desensitized to their trauma experiences, will this in some way impair their
      responding to current or ongoing trauma? The paper addresses practical strategies
      for implementing one evidence-based treatment, Trauma-Focused Cognitive
      Behavioral Therapy (TF-CBT) for youth with ongoing traumas. Collaboration with
      local therapists and families participating in TF-CBT community and international
      programs elucidated effective strategies for applying TF-CBT with these youth.
      These strategies included: (1) enhancing safety early in treatment; (2)
      effectively engaging parents who experience personal ongoing trauma; and (3)
      during the trauma narrative and processing component focusing on (a) increasing
      parental awareness and acceptance of the extent of the youths' ongoing trauma
      experiences; (b) addressing youths' maladaptive cognitions about ongoing traumas;
      and (c) helping youth differentiate between real danger and generalized trauma
      reminders. Case examples illustrate how to use these strategies in diverse
      clinical situations. Through these strategies TF-CBT clinicians can effectively
      improve outcomes for youth experiencing ongoing traumas.

PMID- 21855141
TI  - What's new in ICD-10-CM in classifying child maltreatment?

PMID- 21855142
TI  - Bridging research and practice: challenges and successes in implementing evidence
      based preventive intervention strategies for child maltreatment.
AB  - Child maltreatment has been associated with a wide range of negative
      developmental outcomes for children and families as well as significant economic
      consequences. While efficacious intervention strategies have been demonstrated to
      reduce symptoms of trauma and to improve behavioral and emotional functioning,
      these models have not been widely adopted by clinicians. The challenges
      associated with exporting evidence-based interventions into community settings
      are discussed, along with an example of a preventive intervention program for
      young mothers, successfully implemented through a partnership of community
      agencies and funders.

PMID- 21855143
TI  - Associations of childhood trauma, trauma in adulthood and previous-year stress
      with psychopathology in patients with major depression and borderline personality
      disorder.

PMID- 21855144
TI  - Children-at-risk for poor nutrition: expanding the approach of future
      professionals in educational institutions.
AB  - OBJECTIVES: To examine how the subject of nutrition is being addressed in the
      work with children at risk of poor nutrition in educational institutions and what
      the barriers are which may hinder inclusion of this subject. METHODS: A
      structured questionnaire was constructed for the purpose of this study and was
      implemented with 111 students in Israel who are working in their internships in
      educational institutions with children who are exposed to risk factors of poor
      nutrition (e.g., parental neglect, lack of knowledge, poverty). RESULTS:
      Participants attributed a high level of importance to integrating nutrition
      related components in their work. However, the findings indicate less emphasis on
      nutrition-related components than on psycho-social-educational components, as
      well as a low level of collaboration with specialists in the area of nutrition.
      In addition, it was found that knowledge-based barriers and institutional-related
      systemic barriers may hinder future teachers' capabilities to incorporate those
      components despite their favorable approach towards this subject. CONCLUSIONS:
      The findings illuminate the need to reduce barriers hampering the individual work
      with children at risk of poor nutrition in educational institutions. PRACTICE
      IMPLICATIONS: In the training of future teachers, there is a need to advance a
      bio-psycho-social educational approach incorporating a knowledge base about
      assessing situations of poor nutrition, including how to advance an
      interdisciplinary collaboration with specialists in the area of nutrition.

PMID- 21855145
TI  - Pediatric response to a large-scale child protection intervention.
AB  - OBJECTIVE: In a rural area of the US state of Texas, in April 2008, the Texas
      Department of Family and Protective Services (DFPS) responded to evidence of
      widespread child abuse in an isolated religious compound by removing 463
      individuals into state custody. This mass child protection intervention is the
      largest such action that has ever occurred in the United States. The objective of
      this paper is to characterize the burdens placed on the area's community
      resources, healthcare providers, and legal system, the limitations encountered by
      the forensic and public health professionals, and how these might be minimized in
      future large-scale child protection interventions. METHODS: Drawing on publicly
      available information, this article describes the child abuse investigation,
      legal outcomes, experiences of pediatric healthcare providers directly affected
      by the mass removal, and the roles of regional child abuse pediatric specialists.
      RESULTS: Because the compound's residents refused to cooperate with the
      investigation and the population of the compound was eight times higher than
      expected, law enforcement and child protection resources were insufficient to
      conduct standard child abuse investigations. Local medical and public health
      resources were also quickly overwhelmed. Consulting child abuse pediatricians
      were asked to recommend laboratory and radiologic studies that could assist in
      identifying signs of child abuse, but the lack of cooperation from patients and
      parents, inadequate medical histories, and limited physical examinations
      precluded full implementation of the recommendations. CONCLUSIONS: Although most
      children in danger of abuse were removed from the high-risk environment for
      several months and some suspected abusers were found guilty in criminal trials,
      the overall success of the child protection intervention was reduced by the
      limitations imposed by insufficient resources and lack of cooperation from the
      compound's residents. PRACTICE IMPLICATIONS: Recommendations for community and
      child abuse pediatricians who may become involved in future large child
      protection interventions are presented.

PMID- 21855146
TI  - Repeated malathion exposure induces behavioral impairment and AChE activity
      inhibition in brains of rat pups.
AB  - The present study evaluated if repeated malathion administration would cause
      behavioral impairment in rat pups. Na+K+ ATPase and acetylcholinesterase (AChE)
      activities were investigated in brains of rat pups. Malathion was administered
      (100 or 200 mg/kg) orally (p.o.), once a day for four consecutive days. Rat pups
      were submitted to behavioral tests on the 5th day, 24 h after the last malathion
      administration. Malathion at the dose of 200 mg/kg caused a significant increase
      in the negative geotaxis latency and a decrease in the rotarod latency of rat
      pups. Rat pups exposed to malathion at both doses showed a significant decrease
      in the forelimb support latency and an inhibition of brain AChE activity.
      Repeated exposure of rat pups to malathion caused a decrease in motor
      coordination, vestibular function and muscular strength/coordination. The brain
      activity of AChE is involved in the behavioral alterations caused by malathion in
      rat pups.

PMID- 21855148
TI  - Nucleosomes and C1q bound to glomerular endothelial cells serve as targets for
      autoantibodies and determine complement activation.
AB  - Various studies indicate a role for both anti-nucleosome and anti-C1q
      autoantibodies in glomerulonephritis in patients with systemic lupus
      erythematosus. However, a causal relationship between these autoantibodies and
      the development of lupus nephritis has not been fully established. Since injury
      of the endothelium is a major target in lupus nephritis we assessed the
      interaction of C1q and nucleosomes with glomerular endothelial cells in vitro in
      the presence or absence of autoantibodies against these antigens. We demonstrate
      a direct and dose-dependent binding of both nucleosomes and C1q to immortalized
      human glomerular endothelial cells (GEnC) in vitro, which in part is mediated by
      cell surface heparan sulfate. We demonstrate that nucleosomes and C1q serve as
      targets for monoclonal and polyclonal antibodies as well as for anti-nuclear
      autoantibodies from patients with systemic lupus erythematosus. An additive
      effect of anti-C1q autoantibodies on anti-nucleosome mediated complement
      activation was observed. Furthermore, we showed that the activation of complement
      on glomerular endothelial cells is mediated by the classical pathway since the
      deposition of C3 on GEnC is abrogated by MgEGTA and does not occur in C1q
      depleted serum. Taken together, our studies demonstrate a direct binding of both
      nucleosomes and C1q to glomerular endothelial cells in vitro. The subsequent
      binding of autoantibodies against nucleosomes in patients with systemic lupus
      erythematosus is potentially pathogenic and autoantibodies against C1q seem to
      have an additional effect.

PMID- 21855147
TI  - Differential gene expression and a functional analysis of PCB-exposed children:
      understanding disease and disorder development.
AB  - The goal of the present study is to understand the probable molecular mechanism
      of toxicities and the associated pathways related to observed pathophysiology in
      high PCB-exposed populations. We have performed a microarray-based differential
      gene expression analysis of children (mean age 46.1 months) of Central European
      descent from Slovak Republic in a well-defined study cohort. The subset of
      children having high blood PCB concentrations (>75 percentile) were compared
      against their low PCB counterparts (<25 percentile), with mean lipid-adjusted PCB
      values of 3.02+/-1.3 and 0.06+/-0.03 ng/mg of serum lipid, for the two groups,
      respectively (18.1+/-4.4 and 0.3+/-0.1 ng/ml of serum). The microarray was
      conducted with the total RNA from the peripheral blood mononuclear cells of the
      children using an Affymetrix platform (GeneChip Human genome U133 Plus 2.0 Array)
      and was analyzed by Gene Spring (GX 10.0). A highly significant set of 162
      differentially expressed genes between high and low PCB groups (p value <0.00001)
      were identified and subsequently analyzed using the Ingenuity Pathway Analysis
      tool. The results indicate that Cell-To-Cell Signaling and Interaction, Cellular
      Movement, Cell Signaling, Molecular Transport, and Vitamin and Mineral Metabolism
      were the major molecular and cellular functions associated with the
      differentially altered gene set in high PCB-exposed children. The differential
      gene expressions appeared to play a pivotal role in the development of probable
      diseases and disorders, including cardiovascular disease and cancer, in the PCB
      exposed population. The analyses also pointed out possible organ-specific
      effects, e.g., cardiotoxicity, hepatotoxicity and nephrotoxicity, in high PCB
      exposed subjects. A few notable genes, such as BCL2, PON1, and ITGB1, were
      significantly altered in our study, and the related pathway analysis explained
      their plausible involvement in the respective disease processes, as mentioned.
      Our results provided insight into understanding the associated molecular
      mechanisms of complex gene-environment interactions in a PCB-exposed population.
      Future endeavors of supervised genotyping of pathway-specific molecular
      epidemiological studies and population biomarker validations are already underway
      to reveal individual risk factors in these PCB-exposed populations.

PMID- 21855150
TI  - Effect of immune stress on body weight regulation is altered by ovariectomy in
      female rats.
AB  - It has been suggested that obesity and loss of ovarian function alter the
      inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used
      as a model of human menopause, exhibit both hyperphagia-induced obesity and
      gonadal steroid deficiency. To evaluate the effects of ovariectomy on
      inflammatory responses, we compared the anorectic response to LPS in OVX rats and
      gonad intact female rats. As leptin and hypothalamic interleukin-1beta (IL1beta)
      play pivotal roles in the anorectic response to immune stress, these factors were
      also measured. It was found that the OVX rats exhibited an increased anorectic
      response to LPS compared with the sham-operated rats. The OVX rats showed higher
      serum leptin concentrations and a greater increase in hypothalamic IL1beta mRNA
      expression after LPS injection. In addition, in order to determine whether
      gonadal steroid deficiency contributes to the changes in the inflammatory
      responses of OVX rats, we compared responses between OVX rats treated with
      gonadal steroids and untreated OVX rats. There were no differences in appetite,
      the serum leptin level, and hypothalamic IL1beta mRNA expression between the two
      groups after LPS injection. These findings suggest that the loss of ovarian
      function increases the induction of leptin and hypothalamic IL1beta synthesis and
      consequently increases the anorectic response under immune stress conditions. It
      is possible that these alterations are caused by OVX-induced obesity rather than
      the direct effects of gonadal steroid deficiency.

PMID- 21855149
TI  - Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid
      arthritis: isoform specific regulation of inflammation.
AB  - Pro-inflammatory cytokines and chemokines play critical roles in autoimmune
      diseases including rheumatoid arthritis (RA). Recently, it has been reported that
      beta-arrestin 1 and 2 are involved in the regulation of inflammation. We
      hypothesized that beta-arrestin 1 and 2 play critical roles in murine models of
      RA. Using a collagen-induced arthritis (CIA) and a human TNFalpha transgenic
      (TNFtg) mouse model, we demonstrated that beta-arrestin 1 and 2 expression are
      significantly increased in joint tissue of CIA mice and TNFtg mice. In fibroblast
      like synoviocytes (FLS) isolated from hind knee joint of CIA mice, we observed an
      increase of beta-arrestin 1 and 2 protein and mRNA levels in the early stage of
      arthritis. In FLS, low molecular weight hyaluronan (HA)-induced TNFalpha and IL-6
      production was increased by overexpression of beta-arrestin 1 but decreased by
      overexpression of beta-arrestin 2 demonstrating isoform specific regulation.
      TNFalpha and HA induced an increase of beta-arrestin 1 and 2 expression in FLS,
      while high mobility group box (HMGB)-1 only stimulated beta-arrestin 1
      expression. TNFalpha- or HA-induced beta-arrestin 2 expression was blocked by a
      p38 inhibitor. To examine the in vivo role of beta-arrestin 2 in the pathogenesis
      of arthritis, WT and beta-arrestin 2 KO mice were subjected to collagen antibody
      induced arthritis (CAIA). beta-Arrestin 2 KO mice exhibited more severe arthritis
      in CAIA. Thus beta-arrestin 2 is anti-inflammatory in CAIA. These composite
      observations suggest that beta-arrestin 1 and 2 differentially regulate FLS
      inflammation and increased beta-arrestin 2 may reduce experimental arthritis
      severity.

PMID- 21855151
TI  - Less invasiveness may not always result in less mortality: a meta-analysis of
      transcatheter versus surgical aortic valve replacement for aortic stenosis.

PMID- 21855152
TI  - Pentraxin 3 as a new biomarker of diastolic dysfunction.

PMID- 21855153
TI  - Shorter-term risk of Mycobacterium bovis in Irish cattle following an
      inconclusive diagnosis to the single intradermal comparative tuberculin test.
AB  - In Ireland, new cases of bovine tuberculosis (bTB) are detected using both field
      and abattoir surveillance (More and Good, 2006). Field surveillance is conducted
      through annual testing of all cattle using the single intradermal comparative
      tuberculin test (SICTT). An animal may be deemed a 'standard inconclusive
      reactor' (SIR) to the SICTT if the bovine response is >2mm and between 1 and
      4mm>the avian response. The herdowner then has three choices for the management
      of the SIR: option 1 is to have the animal retested after a minimum period of 42
      days (an inconclusive reactor retest, IRR), option 2 is to slaughter the SIR and,
      provided the animal has no visible lesions, have a full herd test 42 days after
      the SIR leaves the herd, option 3 is to slaughter the SIR and have the lymph
      nodes examined using histology and/or culture for bTB. In the current study, we
      examine the bTB risk for SIRs both at slaughter prior to the IRR and at the IRR,
      and the future bTB risk of TIR animals (so-called 'transient SIRs'; SIR animals
      with a negative SICTT result at the subsequent IRR) that moved from the herd of
      disclosure within 6 months of the IRR. We also investigate factors associated
      with the future bTB status of SIRs at slaughter prior to the IRR and at the IRR.
      The study population included all SIRs identified in Ireland between 2005 and
      2009 inclusive in a herd otherwise Officially TB free (OTF). Between 11.8% and
      21.4% of SIRs slaughtered prior to the IRR were confirmed bTB positive at post
      mortem (using histology or culture if histology was not definitive), compared to
      0.13-0.22% of SICTT -ve cohort animals. The post mortem bTB lesion rate of SIRs
      is lower than the lesion rate reported for reactor animals between 2005 and 2009
      of between 34% and 39%, reflecting the doubtful infection status of these
      animals. Between 20.3% and 27.9% of herds were restricted at the IRR. The herd
      restriction rate amongst the national herd between 2005 and 2009 varied from
      5.09% to 6.02%. TIRs that moved out of the disclosing herd within 6 months of the
      IRR were 12 times more likely to be bTB positive at the next test/slaughter
      compared to all animals in the national herd. The same increased risk did not
      apply to the SICTT -ve cohort animals that moved out of the same herds at the
      same time. Based on a range of measures, SIRs and TIRs are each at increased bTB
      risk into the future. Consequently, differential treatment of TIR animals would
      be justified.

PMID- 21855154
TI  - "It's driving her mad": Gender differences in the effects of commuting on
      psychological health.
AB  - Commuting is an important component of time use for most working people. We
      explore the effects of commuting time on the psychological health of men and
      women. We use data from the British Household Panel Survey in a fixed effects
      framework that includes variables known to determine psychological health, as
      well as factors which may provide compensation for commuting such as income, job
      satisfaction and housing quality. Our results show that, even after these
      variables are considered, commuting has an important detrimental effect on the
      psychological health of women, but not men, and this result is robust to numerous
      different specifications. We explore explanations for this gender difference and
      can find no evidence that it is due to women's shorter working hours or weaker
      occupational position. Rather women's greater sensitivity to commuting time seems
      to be a result of their larger responsibility for day-to-day household tasks,
      including childcare and housework.

PMID- 21855155
TI  - Physicians on board: an examination of physician financial interests in ASCs
      using longitudinal data.
AB  - This paper investigates physician financial interests in ambulatory surgery
      centers (ASCs) using novel, longitudinal data that identify board members
      (directors) of ASCs in Florida. Improving on prior research, the estimated models
      in this paper disentangle physician director selection effects from the causal
      impact of these financial interests. The data suggest that even prior to their
      financial interest, physician directors had larger procedure volumes than non
      directors. Physician directors also referred more lower-risk patients. On
      average, ASC board membership led to a 27% increase in a physician's procedure
      volume and a 16% increase in a physician's colonoscopy volume. Simulations
      suggest that 5% of the colonoscopies performed in Florida between 1997 and 2004
      may have been due to physician ASC board membership. The evidence also suggests
      that physician directors steered patients from hospitals to their affiliate ASCs.
      In addition, they referred and/or treated more lower-risk patients as a result of
      board membership.

PMID- 21855157
TI  - Changes in the arginine methylation of organ proteins during the development of
      diabetes mellitus.
AB  - AIM: In this study, we examined changes in asymmetric dimethylarginine (ADMA),
      dimethylarginine dimethylaminohydrolase (DDAH), nitric oxide synthesis (NOS), and
      the arginine methylation of organ proteins during the development of diabetes in
      mice. METHODS: Db/db mice developed significant obesity and fasting hyperglycemia
      during diabetogenesis. During diabetogenesis, the expression of ADMA and nNOS was
      increased, while that of DDAH1 and protein-arginine methyltransferase 1 (PRMT1)
      was decreased. Additionally, arginine methylation in the liver and adipose tissue
      was altered during diabetogenesis. RESULTS: Changes were evident at 75, 60, and
      52 kDa in liver tissue and at 38 and 25 kDa in adipose tissue. Collectively, DDAH
      and ADMA are closely associated with the development of obesity and diabetes, and
      the arginine methylation levels of certain proteins were changed during diabetes
      development. CONCLUSION: Protein arginine methylation plays a role in the
      pathogenesis of diabetes.

PMID- 21855156
TI  - Occurrence of fastidious Campylobacter spp. in fresh meat and poultry using an
      adapted cultural protocol.
AB  - This study used an adapted cultural protocol for the recovery of fastidious
      species of Campylobacter, to gain a more accurate understanding of the diversity
      of Campylobacter populations in fresh meats. Chicken (n=185), pork (n=179) and
      beef (n=186) were collected from supermarkets and butchers throughout the
      Republic of Ireland. Samples were enriched in Campylobacter enrichment broth for
      24h under an atmosphere of 2.5% O(2), 7% H(2), 10% CO(2), and 80.5% N(2). The
      enriched samples were then filtered onto non-selective Anaerobe Basal Agar
      supplemented with lysed horse blood using mixed ester filter membranes. Isolates
      were identified by both genus and species-specific PCR assays and biochemical
      testing. The incidence of campylobacters on beef (36%) was significantly higher
      than on pork (22%) or chicken (16%), and far exceeds previously reported
      prevalence levels. The method was successful in recovering 7 species of
      Campylobacter, including the fastidious spp. C. concisus and C. mucosalis, from
      chicken meat, and 10 species, including C. concisus, C. curvus, C. mucosalis, C.
      sputorum, and C. upsaliensis, from minced beef. The isolation of C. concisus and
      C. upsaliensis from meat in this study is of particular significance, due to
      their emerging clinical relevance. The results of this study confirm that the
      diversity of Campylobacter species on fresh meats is greater than previously
      reported and highlights the bias of cultural methods towards the recovery of C.
      jejuni.

PMID- 21855158
TI  - Level of serum IL-12 and its correlation with endothelial dysfunction, insulin
      resistance, proinflammatory cytokines and lipid profile in newly diagnosed type 2
      diabetes.
AB  - AIM: This study was an attempt to evaluate and correlate serum interleukin-12 (IL
      12) with different circulating markers in newly diagnosed type-2 diabetes
      mellitus (T2DM) for possible progression of atherosclerosis. METHODS: For this
      study, we recruited 1968 family members of diabetics and 349 had abnormal
      glucose. Out of 349 subjects, 197 were T2DM as per American Diabetes Association
      guidelines and further investigated for cardiovascular abnormalities. 63 T2DM
      have high sensitive C-reactive protein (hsCRP)>3.0mg/l and cardiovascular
      complications. Overall, 150 subjects, 50 healthy, 50 T2DM (D1) and 50 T2DM with
      cardiovascular complications (D2) were enrolled and investigated for soluble
      markers. RESULTS: The levels of serum glucose, proinflammatory cytokines (IL-6,
      IL-12, tumor necrosis factor), endothelial dysfunction markers [vascular cell
      adhesion molecule-1 (VCAM-1), inter-cellular adhesion molecule-1 (ICAM-1), nitric
      oxide] and lipid abnormality were highest in D2 group. Correlation and regression
      study showed that IL-12 was dependent on hsCRP, insulin resistance, VCAM-1, ICAM
      1 and lipids. The multivariate stepwise regression analysis demonstrates that
      hsCRP contributes significantly for variance of IL-12. CONCLUSION: This study
      reveals that, even first-time diagnosis of T2DM, subjects with higher insulin
      resistance and abnormal lipids have elevated IL-12, endothelial dysfunction and
      proinflammatory markers. Further increased hsCRP enhance IL-12 which up-regulate
      cardiovascular disease progression.

PMID- 21855159
TI  - Early-onset type 2 diabetes: high risk for premature diabetic retinopathy.
AB  - AIM: To examine the relationship between early-onset type 2 diabetes (T2D) and
      retinopathy in relation to the burden, severity, the extent of its premature
      development and associated predictive risk factors. METHODS: A cross sectional
      study using the hospital diabetes register and eye screening database to identify
      T2D subjects and to ascertain retinopathy severity. Early and later-onset cohort
      were defined as age of diagnosis <40 and >40 years respectively. RESULTS: 2516
      subjects were identified of which 455 were diagnosed below 40 years. After 10
      years of diagnosis, the prevalence of overall retinopathy was significantly
      higher in the early-onset cohort (p < 0.05). For significant retinopathy (SigDR),
      there was a non-significant trend of higher prevalence with increasing diabetes
      duration in the early-onset cohort. The rate of increase for SigDR was greater in
      the early-onset cohort who experienced similar burden of SigDR up to 20 years
      earlier than the later-onset cohort. Hypertension (p < 0.05), suboptimal
      glycaemic control (p < 0.05) and long diabetes duration (p < 0.05) were
      associated with risk of retinopathy whilst lower age of diagnosis and
      dyslipidaemia were not significant predictive factors. CONCLUSIONS: Early-onset
      T2D subjects are at risk of developing premature retinopathy driven predominantly
      by hypertension and prolonged exposure to suboptimal diabetes control.

PMID- 21855160
TI  - Effect of sitagliptin monotherapy on serum total ghrelin levels in people with
      type 2 diabetes.
AB  - AIM: Sitagliptin is not associated with weight gain and has neutral effects on
      body weight. It is unclear whether sitagliptin treatment alters serum ghrelin
      levels in people with type 2 diabetes. METHODS: Forty-four subjects with type 2
      diabetes were randomly assigned to receive sitagliptin or medical nutrition
      therapy (MNT) for 12 weeks. Changes in anthropometric variables, glycemic
      control, insulin resistance, lipid parameters, and total ghrelin levels were
      evaluated at baseline and following 12 weeks of treatment. RESULTS: Significant
      decreases in body weight and body mass index were observed over the entire study
      period in both treatment groups. Glycosylated hemoglobin and postprandial plasma
      glucose levels were statistically significant decreased in the groups receiving
      sitagliptin compared with baseline values (p=0.021 and p=0.021, respectively),
      while they were unchanged in the groups receiving MNT. There was a significant
      decrease in total ghrelin in the groups receiving sitagliptin (p=0.04) compared
      with baseline values but not in the groups receiving MNT (p=0.46) at the end of
      the 12 weeks. CONCLUSIONS: In this study of patients with type 2 diabetes,
      treatment with sitagliptin was associated with a significant decrease in serum
      ghrelin levels. These results suggest that the neutral effect of sitagliptin on
      weight might be associated with the suppression of fasting serum ghrelin levels.

PMID- 21855161
TI  - Hypertriglyceridaemia either in isolation or in combination with abdominal
      obesity is strongly associated with atherogenic dyslipidaemia in Asian Indians.
AB  - AIM: To assess the prevalence of isolated hypertriglyceridaemia (iHTG) and
      hypertriglyceridaemic waist phenotype (HTWP) in urban adult Asian Indian
      population and to study their associations with atherogenic dyslipidaemia.
      METHODS: Data of an epidemiological survey (n=2117, M:F 1007:1110) was used.
      Prevalences of iHTG (fasting triglycerides (TG) >= 1.7 mmol/l) and HTWP (waist
      circumference male >= 90 cm and female >= 80 cm and TG >= 1.7 mmol/l), were
      assessed. Their prevalences in relation to glucose intolerance were also studied.
      Associations of iHTG and HTWP with the occurrence of atherogenic dyslipidaemia
      indicated by elevated LDL-C/HDL-C ratio of >=2.5 were assessed using multiple
      logistic regression analyses. RESULTS: iHTG, and HTWP were present in 13.4% and
      17.8% respectively. Prevalence of HTWP was significantly higher among women.
      Prevalence of HTWP progressively increased with glucose intolerance. Nearly 60%
      of the subjects with iHTG or HTWP had atherogenic dyslipidaemia and prevalence
      was similar in both groups. CONCLUSIONS: Hypertriglyceridaemia, present either as
      iHTG or HTWP was strongly associated with atherogenic dyslipidaemia.
      Dyslipidaemia occurred more frequently in glucose intolerance since the
      prevalence of both forms of hypertriglyceridaemia increased with glucose
      intolerance.

PMID- 21855162
TI  - The expression of transcription factor 7-like 2 (TCF7L2) in fat and placental
      tissue from women with gestational diabetes.
AB  - In the present study we showed that the expression of transcription factor 7-like
      2 (TCF7L2) mRNA in visceral adipose tissue obtained from 20 women with
      gestational diabetes was lower than in 18 pregnant women with normal glucose
      tolerance (p = 0.02), however after adjusting for BMI values, the difference was
      not significant.

PMID- 21855163
TI  - Automated PET-guided liver segmentation from low-contrast CT volumes using
      probabilistic atlas.
AB  - The use of the functional PET information from PET-CT scans to improve liver
      segmentation from low-contrast CT data is yet to be fully explored. In this
      paper, we fully utilize PET information to tackle challenging liver segmentation
      issues including (1) the separation and removal of the surrounding muscles from
      liver region of interest (ROI), (2) better localization and mapping of the
      probabilistic atlas onto the low-contrast CT for a more accurate tissue
      classification, and (3) an improved initial estimation of the liver ROI to speed
      up the convergence of the expectation-maximization (EM) algorithm for the
      Gaussian distribution mixture model under the guidance of a probabilistic atlas.
      The primary liver extraction from the PET volume provides a simple mechanism to
      avoid the complicated pre-processing of feature extraction as used in the
      existing liver CT segmentation methods. It is able to guide the probabilistic
      atlas to better conform to the CT liver region and hence helps to overcome the
      challenge posed by liver shape variability. Our proposed method was evaluated
      against manual segmentation by experienced radiologists. Experimental results on
      35 clinical PET-CT studies demonstrated that our method is accurate and robust in
      automated normal liver segmentation.

PMID- 21855164
TI  - ALK translocation is associated with ALK immunoreactivity and extensive signet
      ring morphology in primary lung adenocarcinoma.
AB  - BACKGROUND: ALK rearrangement is particularly observed in signet-ring sub-type
      adenocarcinoma. Since fluorescence in situ hybridization (FISH) is not suitable
      for mass screening, we aimed to characterize the predictive utility of tumour
      morphology and ALK immunoreactivity to identify ALK rearrangement, in a primary
      lung adenocarcinoma dataset enriched for signet-ring morphology, compared with
      that of other morphology. METHODS: 7 adenocarcinomas from diagnostic archives
      reported with signet-ring morphology were assessed and compared with 11
      adenocarcinomas without signet-ring features over the same time period. Growth
      patterns were reviewed, ALK expression was assessed by standard
      immunohistochemistry using ALK1 clone and Envision detection (Dako), and ALK
      rearrangement was assessed by FISH (Abbott Molecular). Associations between
      groups and predictive utility of tumour morphology and ALK expression using FISH
      as gold standard were calculated. RESULTS: 2 excision lung biopsy cases with pure
      (100%) signet-ring morphology and solid patterns demonstrated diffuse moderate
      cytoplasmic ALK immunoreactivity (2+) and harboured ALK rearrangements (p=0.007),
      unlike 5 mixed-signet-ring and 11 non-signet-ring adenocarcinomas, which showed
      negative or 1+ immunoreactivity; and did not harbour ALK rearrangements (p>0.1).
      ALK expression was not associated with ALK copy number. 6 of 7 cases with signet
      ring morphology stained for TTF-1. Pure signet-ring morphology and moderate ALK
      expression were both associated with ALK rearranged tumours. CONCLUSION: ALK
      rearrangement is strongly associated with ALK immunoreactivity, and was seen only
      in tumours with pure signet-ring morphology and solid growth pattern. Tumour
      morphology, growth pattern and ALK immunoreactivity appear to be good indicators
      of ALK rearrangement, with TTF-1 positivity aiding in proving primary pulmonary
      origin.

PMID- 21855166
TI  - In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in
      COPD.
AB  - Novel pharmacological strategies are aimed at the resolution of systemic
      inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis.
      Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline
      acetyltransferase (ChAT) participate in the airway inflammation of COPD, their
      role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from
      COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V
      binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3)
      choline levels in serum and PBT-cells extracts. We tested the effects of
      Tiotropium (Spiriva((r))) and hemicholinium-3 (HCh-3) on apoptosis, NFkappaB
      pathway, caspases 3 and 8 activity and choline levels, in PBT-cells from COPD
      patients. We showed that: (1) apoptosis, mAChR M(3) and ChAT expression and the
      CD3+ and CD8+ ACh-binding are increased in PBT-cells from COPD patients when
      compared to C subjects, while CD4+/CD8+ ratio of ACh-binding to PBT cells was
      reduced in COPD; (2) choline levels are higher in serum and PBT-cells extracts
      from COPD patients than in S and C; (3) Tiotropium and HCh-3 reduced CD4+ and
      increased CD8+ apoptosis via caspases 3 and 8 activities and via IkappaB mediated
      mechanisms in COPD patients. This study suggests the involvement of non-neuronal
      components of cholinergic system in the regulation of PBT-cell apoptosis in COPD
      and demonstrates that Tiotropium regulates CD4+ and CD8+ PBT-cell apoptosis. It
      provides novel putative pharmacological targets for the resolution of systemic
      inflammation in COPD.

PMID- 21855165
TI  - Complement-mediated injury and protection of endothelium: lessons from atypical
      haemolytic uraemic syndrome.
AB  - The complement system provides a vital defence against invading pathogens. As an
      intrinsic system it is always 'on', in a state of constant, low level activation.
      This activation is principally mediated through the deposition of C3b on to
      pathogenic surfaces and host tissues. C3b is generated by spontaneous 'tick over'
      and formal activation of the alternative pathway, and by activation of the
      classical and lectin pathways. If the deposited C3b is not appropriately
      regulated, there is progression to terminal pathway complement activation via the
      C5 convertases, generating the potent anaphylotoxin C5a and the membrane attack
      complex C5b-9. Unsurprisingly, these highly active components have the potential
      to cause injury to bystander host tissue, including the vascular endothelium. As
      such, complement activation on endothelium is normally tightly controlled by a
      large number of fluid-phase and membrane bound inhibitors, in an attempt to
      ensure that propagation of complement activation is appropriately restricted to
      invading pathogens and altered 'self', e.g. apoptotic and necrotic cells. The
      kidney is increasingly recognised as a site at particular risk from complement
      mediated endothelial injury. Both genetic and acquired defects which impact on
      complement regulation predispose to this susceptibility. The thrombotic
      microangiopathy, haemolytic uraemic syndrome (HUS), will be used to illustrate
      the mechanisms by which the endothelial cell injury occurs. Finally, the
      underlying rationale for current and future potential therapeutic interventions
      in HUS and also the opportunities for enhancing endothelial defence to prevent
      relapsing disease through increased complement cytoprotective strategies will be
      summarised.

PMID- 21855167
TI  - B-1 lymphocytes differentiate into functional osteoclast-like cells.
AB  - The existence of murine peritoneal osteoclast precursors has been already
      described. Also, recent reports evidenced an interplay between B lymphocytes and
      osteoclasts development. B-1 cells comprise a B-lymphocyte subset that resides
      mostly in pleural and peritoneal cavities. It has been demonstrated that B-1
      cells can differentiate into mononuclear phagocytes and form multinucleated giant
      cells. Based on these findings, we investigated the role of B-1 lymphocytes in
      bone resorption and osteoclastogenesis. In vivo experimental periodontitis
      induced in B-1 deficient Xid mice demonstrated that bone resorption is impaired
      in these animals. However, reconstitution of Xid mice with B-1 cells increased
      bone resorption to near Balb/c values. B-1 cell derived phagocytes express the
      receptor activator of nuclear factor-kappaB (RANK) and the macrophage colony
      stimulating factor receptor (M-CSFR). When cultured with RANK-ligand (RANKL) and
      M-CSF, B-1 cells became tartrate resistant acid phosphatase (TRAP) positive
      multinucleated cells, a typical osteoclast phenotype. Lacunae formation was
      observed when cells were cultivated onto a calcium phosphate analog, indicating
      functional differentiation of B1 cells into osteoclast-like cells. The dynamics
      of their IgM expression showed that this lymphoid marker was downregulated along
      the differentiation of B-1 lymphocytes into osteoclasts. Our results unveiled the
      first evidence that B-1 cells have a role in osteoclastogenesis and bone
      resorption and offer new insights in the relationship between bone and lymphoid
      cells.

PMID- 21855168
TI  - Functional modulation of human monocytes derived DCs by anaphylatoxins C3a and
      C5a.
AB  - Anaphylatoxins C3a and C5a are important modulators for dendritic cell activation
      and function in mice. In order to verify the significance of these observations
      in man, we have investigated the functional modulation of human monocytes derived
      DCs by C3a and C5a. Here we report that engagement of C3aR or C5aR on human
      monocytes derived DCs (moDCs) enhances the cell activation and their capacity for
      allostimulation. In addition, we show that intracellular production of cAMP is
      reduced and PI3K/AKT, ERK and NF-kappaB signalling is increased following
      stimulation with C3a or C5a, identifying intracellular signalling pathways that
      could convert cell surface C3aR and C5aR engagement into changes in moDC
      functions. Our data provide evidence that human DCs are equipped to react to
      C3a/C5a and undergo phenotypic change as well as functional modulation.
      Complement offers a potential route to modulate human DC function and regulate T
      cell mediated immunity.

PMID- 21855169
TI  - GsGASA1 mediated root growth inhibition in response to chronic cold stress is
      marked by the accumulation of DELLAs.
AB  - Low, but not freezing temperatures are a major factor limiting plant vegetative
      growth and development. It is not clear what signaling mechanism is used to limit
      plant growth in response to chronic low temperatures, thus it is important to
      continue to isolate and characterize genes whose activity/expression correlate
      well with cold responses. In this study, a novel GASA gene was isolated from
      Glycine soja and named GsGASA1. Quantitative real-time PCR analysis indicated
      that GsGASA1 expression responded to exogenous gibberellic acid (GA) and abscisic
      acid (ABA) treatments. Compared with wild-type plants under long-term cold
      treatment, the constitutive expression of GsGASA1 in transgenic Arabidopsis
      plants enhanced the inhibition of root elongation, while also increasing the
      transcript levels of RGL2 and RGL3, two of five DELLA genes in Arabidopsis. DELLA
      is a class of transcriptional regulators in GA signaling pathway restraining
      plant growth. Our results imply that GsGASA1 participates in chronic cold-induced
      root growth inhibition with the accumulation of DELLA genes. Lastly, a
      subcellular localization study using a yellow fluorescent protein (YFP) fusion
      protein indicated that GsGASA1 was localized to the plasma membrane, cytoplasm
      and nucleus.

PMID- 21855171
TI  - Medical relief after earthquakes: it's time for a new paradigm.

PMID- 21855170
TI  - Allocating scarce resources in disasters: emergency department principles.
AB  - Decisions about medical resource triage during disasters require a planned
      structured approach, with foundational elements of goals, ethical principles,
      concepts of operations for reactive and proactive triage, and decision tools
      understood by the physicians and staff before an incident. Though emergency
      physicians are often on the front lines of disaster situations, too often they
      have not considered how they should modify their decisionmaking or use of
      resources to allow the "greatest good for the greatest number" to be
      accomplished. This article reviews key concepts from the disaster literature,
      providing the emergency physician with a framework of ethical and operational
      principles on which medical interventions provided may be adjusted according to
      demand and the resources available. Incidents may require a range of responses
      from an institution and providers, from conventional (maximal use of usual space,
      staff, and supplies) to contingency (use of other patient care areas and
      resources to provide functionally equivalent care) and crisis (adjusting care
      provided to the resources available when usual care cannot be provided). This
      continuum is defined and may be helpful when determining the scope of response
      and assistance necessary in an incident. A range of strategies is reviewed that
      can be implemented when there is a resource shortfall. The resource and staff
      requirements of specific incident types (trauma, burn incidents) are briefly
      considered, providing additional preparedness and decisionmaking tactics to the
      emergency provider. It is difficult to think about delivering medical care under
      austere conditions. Preparation and understanding of the decisions required and
      the objectives, strategies, and tactics available can result in better-informed
      decisions during an event. In turn, adherence to such a response framework can
      yield thoughtful stewardship of resources and improved outcomes for a larger
      number of patients.

PMID- 21855172
TI  - Posterior cingulate atrophy and metabolic decline in early stage Alzheimer's
      disease.
AB  - To test the hypothesis that Alzheimer's disease (AD) patients with posterior
      cingulate/precuneus (PCP) atrophy would be a distinct disease form in view of
      metabolic decline. Eighty-one AD patients underwent (18)F-fluorodeoxyglucose
      (FDG) positron emission tomography (PET) and structural magnetic resonance
      imaging (MRI). Positron emission tomography and voxel-based morphometry (VBM) Z
      score maps were generated for the individual patients using age-specific normal
      databases. The patients were classified into 3 groups based on atrophic patterns
      (no-Hipp-PCP, atrophy in neither hippocampus nor PCP; Hipp, hippocampal atrophy;
      PCP, PCP atrophy). There were 16 patients classified as no-Hipp-PCP, 55 as Hipp,
      and 10 as PCP. The Mini Mental State Examination (MMSE) score was similar among
      the groups. The greater FDG decline than atrophy was observed in all groups,
      including the no-Hipp-PCP. The PCP group was younger, and was associated with a
      greater degree of FDG decline in PCP than the others. There are diverse atrophic
      patterns in a spectrum of AD. In particular, a subset of patients show PCP
      atrophy, which is associated with greater metabolic burden.

PMID- 21855174
TI  - Sodium intake and physical activity impact cognitive maintenance in older adults:
      the NuAge Study.
AB  - This study examines the association between sodium intake and its interaction
      with physical activity on cognitive function over 3 years in older adults
      residing in Quebec, Canada. We analyzed a subgroup from the NuAge cohort (aged 67
      84 years) with nutrient intake data, including sodium, from a food frequency
      questionnaire administered at baseline. Baseline physical activity was assessed
      using the Physical Activity Scale for the Elderly (PASE; high-low). Modified Mini
      Mental State Examination (3MS) was administered at baseline and annually for 3
      additional years. Controlling for age, sex, education, waist circumference,
      diabetes, and dietary intakes, analyses showed an association between sodium
      intake and cognitive change over time in the low PASE group only. Specifically,
      in the low PASE group, elders in the low sodium intake tertile displayed better
      cognitive performance over time (mean decline in 3MS over years: mean [M] = 
      0.57, standard error [SE] = 0.002) compared with the highest (M = -1.72, SE =
      0.01) and mid sodium intake (M = -2.07, SE = 0.01) groups. This finding may have
      significant public health implications, emphasizing the importance of addressing
      multiple lifestyle factors rather than a single domain effect on brain health.

PMID- 21855173
TI  - Cognitive response to estradiol in postmenopausal women is modified by high
      cortisol.
AB  - Estradiol has potent favorable effects on brain function and behavior in animals
      while in human trials, the results are inconsistent. A number of potential
      mediating variables influencing response to estradiol have been proposed to
      account for this variability, 1 of which includes stress. We conducted a placebo
      controlled study to examine joint and independent effects of estradiol and
      elevated levels of the stress hormone cortisol on cognition and biomarkers of
      aging and neurodegenerative disease. Thirty-nine healthy postmenopausal women (56
      84 years) received 0.10 mg/dL of transdermal 17beta-estradiol (E2) or placebo for
      8 weeks. During the last 4 days of the trial, subjects also received 90 mg/day
      (30 mg 3*/day) of oral hydrocortisone (CORT) to induce stress-level elevations in
      cortisol, or a matched placebo. The 4 groups thus included placebo (placebo
      patch/placebo pill), CORT-alone (placebo patch/hydrocortisone), E2-alone
      (estradiol patch/placebo pill), and E2+CORT (estradiol patch/hydrocortisone).
      Eight weeks of E2 increased plasma estradiol by 167%, and 4 days of CORT
      increased plasma cortisol by 119%. Overall, E2 had favorable effects on verbal
      memory (p = 0.03), working memory (p = 0.02), and selective attention (p = 0.04),
      and the magnitude of these effects was attenuated for E2+CORT. E2-alone and
      E2+CORT had opposing effects on plasma levels of the amyloid-beta (Abeta)
      biomarker (Abeta40/42 ratio, p < 0.05), with the more favorable response observed
      for E2-alone. CORT-induced increases in insulin-like growth factor-1 were blunted
      by E2 coadministration. Our findings indicate that cognitive and physiological
      responses to estradiol are adversely affected by elevated stress hormone levels
      of cortisol in healthy postmenopausal women.

PMID- 21855176
TI  - [Endoscopic diagnosis of intussusception due to Meckel's diverticulum].

PMID- 21855177
TI  - [Endoscopic capsule: position paper of the Catalan Society of Gastroenterology].

PMID- 21855175
TI  - 3xTgAD mice exhibit altered behavior and elevated Abeta after chronic mild social
      stress.
AB  - Chronic stress may be a risk factor for developing Alzheimer's disease (AD), but
      most studies of the effects of stress in models of AD utilize acute adverse
      stressors of questionable clinical relevance. The goal of this work was to
      determine how chronic psychosocial stress affects behavioral and pathological
      outcomes in an animal model of AD, and to elucidate underlying mechanisms. A
      triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice
      were used to test for an affect of chronic mild social stress on blood glucose,
      plasma glucocorticoids, plasma insulin, anxiety, and hippocampal amyloid beta
      particle (Abeta), phosphorylated tau (ptau), and brain-derived neurotrophic
      factor (BDNF) levels. Despite the fact that both control and 3xTgAD mice
      experienced rises in corticosterone during episodes of mild social stress, at the
      end of the 6-week stress period 3xTgAD mice displayed increased anxiety, elevated
      levels of Abeta oligomers and intraneuronal Abeta, and decreased brain-derived
      neurotrophic factor levels, whereas control mice did not. Findings suggest 3xTgAD
      mice are more vulnerable than control mice to chronic psychosocial stress, and
      that such chronic stress exacerbates Abeta accumulation and impairs neurotrophic
      signaling.

PMID- 21855178
TI  - [Precautions required on using the predictive thresholds of the FRAX(r) tool to
      decide the need for an axial bone density scan in the Spanish population].

PMID- 21855179
TI  - [Recurrence of hyperthyroidism in a female patient with thyroidectomized Grave's
      disease diagnosed 15 years earlier].

PMID- 21855180
TI  - [Catalase-negative Staphylococcus aureus subsp. aureus: a new case in Spain].

PMID- 21855181
TI  - New fluorine-containing hydrazones active against MDR-tuberculosis.
AB  - Several new fluorine-containing hydrazones were synthesized and screened for
      their in vitro antimycobacterial activity. Nine of these derivatives have shown a
      remarkable activity against MDR-TB strain with MIC 0.5 MUg/mL and high value of
      selectivity index (SI). Compound 3h with the highest SI (1268.58) was used for
      stability evaluation with putative metabolites (ciprofloxacin and
      formylciprofloxacin) detection. Compound 3h was stable at pH 7.4 of aqueous
      buffer and rat plasma, in acidic buffers (at pH 3 and 5) slow decomposition was
      observed. Interestingly, no formylciprofloxacin was detected in the solution, and
      only slightly increased concentration of ciprofloxacin was observed instead.
      Trifluoromethyl hydrazones 3f and 3g exhibited the best activity also against two
      strains of Mycobacterium kansasii (MIC 1-4 MUmol/L). All evaluated compounds were
      found to be non-cytotoxic.

PMID- 21855182
TI  - Synthesis of 3-heteroarylthioquinoline derivatives and their in vitro
      antituberculosis and cytotoxicity studies.
AB  - A series of 3-heteroarylthioquinoline derivatives has been synthesized by the
      Friedlander annulation of 2-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-1-aryl-1
      ethanone/2-(1,3-benzothiazol-2-ylsulfanyl)-1-aryl-1-ethanone/1-aryl-2-[(2-phenyl
      2H-1,2,3,4-tetraazol-5-yl)sulfanyl]-1-ethanone with 2-aminobenzophenone in good
      yields using YbCl(3) as the catalyst. These compounds have been screened for
      their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and among
      the 21 compounds screened, 2-[2-(4-bromophenyl)-4-phenyl-3-quinolyl]sulfanyl-5
      methyl-1,3,4-thiadiazole (5d) and 2-[2-(4-chlorophenyl)-4-phenyl-3
      quinolyl]sulfanyl-5-methyl-1,3,4-thiadiazole (5c) were found to be the most
      active compounds with MIC of 3.2 and 3.5 MUM respectively against MTB. The
      cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro were evaluated for
      5c and 5d, which displayed no toxic effects (IC(50) > 1000 MUM) against the mouse
      fibroblast cell line NIH 3T3.

PMID- 21855183
TI  - Novel C-4'' modified azithromycin analogs with remarkably enhanced activity
      against erythromycin-resistant Streptococcus pneumoniae: the synthesis and
      antimicrobial evaluation.
AB  - Three novel structural series of C-4'' modified azithromycin analogs with two
      amide groups, which were connected by different alkyl linkage, were designed,
      prepared and evaluated for their in vitro antibacterial activity against seven
      phenotypes of respiratory pathogens. Among them, 7d, 8j and 9j, as
      representatives of corresponding series, exhibited remarkably improved activity
      against erythromycin-resistant Streptococcus pneumoniae expressing the erm gene,
      the mef gene, and the erm and mef genes. In addition, 7a-c, 7f-h, 7j, 8d, 8g, 8i,
      9a-b and 9i displayed favorable efficacy against erythromycin-resistant S.
      pneumoniae A22072 expressing the mef gene.

PMID- 21855184
TI  - [Severe hypoglycemia induced by tramadol: two new cases of an unlisted side
      effect].
AB  - INTRODUCTION: Tramadol is a weak opioid analgesic used as a step two analgesic,
      approved in France for the treatment of moderate to severe pain in adult
      patients. The most common side effects are gastrointestinal and neurologic.
      Hypoglycaemia is an almost unknown side effect. CASE REPORTS: We report two
      patients who presented with severe hypoglycaemia related to oral administration
      of tramadol in non diabetic patients. The underlying mechanisms of hypoglycaemia
      induced by tramadol are unclear. The only weak opioid analgesic drug reported to
      cause hypoglycaemia is propoxyphene, which has been widely used in France. The
      recent withdrawal of dextropropoxyphene in France might increase the
      prescriptions of tramadol and healthcare professionals should be aware of the
      risk of hypoglycaemia. CONCLUSION: The risk of hypoglycaemia should be added to
      the summary of product characteristics of tramadol.

PMID- 21855186
TI  - Supernumerary teeth and gemination.

PMID- 21855185
TI  - Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer
      cachexia?
AB  - BACKGROUND & AIMS: Despite the descriptive presence of cancer cachexia (CC) in
      clinical practice, the underlying mechanisms and diagnostic definition have not
      been clearly identified. Recent work, attempting to establish diagnostic and
      staging criteria for CC, has identified IL-6 as a biomarker. This study aimed to
      investigate the clinical relevance of plasma levels of four pro-inflammatory
      cytokines (IL-6, IL-1beta, IL-8 and TNF-alpha) in advanced cancer patients (ACP)
      to further establish their potential in the diagnostic definition of CC. METHODS:
      Blood was obtained from 83 ACP (47 male and 36 female, aged 34-85 years) and
      analyzed for white blood cells, lymphocytes, C-reactive protein, albumin and
      cytokines. Subjects completed questionnaires to establish weakness, loss of
      appetite, fatigue, quality of life and weight loss; completed tests to determine
      strength, body composition and sarcopenia; and consented to chart review to
      calculate survival and total days admitted to hospital. RESULTS: This study shows
      that, in ACP, IL-1beta is better associated with clinical features of the
      cachectic condition, such as weakness, loss of appetite, weight loss and
      sarcopenia, than IL-6. CONCLUSION: IL-6 may not best represent the clinical
      correlates of CC in ACP. Additional cytokines should be considered in the
      definition of this condition.

PMID- 21855187
TI  - A review of biochars' potential role in the remediation, revegetation and
      restoration of contaminated soils.
AB  - Biochars are biological residues combusted under low oxygen conditions, resulting
      in a porous, low density carbon rich material. Their large surface areas and
      cation exchange capacities, determined to a large extent by source materials and
      pyrolysis temperatures, enables enhanced sorption of both organic and inorganic
      contaminants to their surfaces, reducing pollutant mobility when amending
      contaminated soils. Liming effects or release of carbon into soil solution may
      increase arsenic mobility, whilst low capital but enhanced retention of plant
      nutrients can restrict revegetation on degraded soils amended only with biochars;
      the combination of composts, manures and other amendments with biochars could be
      their most effective deployment to soils requiring stabilisation by revegetation.
      Specific mechanisms of contaminant-biochar retention and release over time and
      the environmental impact of biochar amendments on soil organisms remain somewhat
      unclear but must be investigated to ensure that the management of environmental
      pollution coincides with ecological sustainability.

PMID- 21855188
TI  - Relation of sex and estrogen therapy to serum fibroblast growth factor 23, serum
      phosphorus, and urine phosphorus: the Heart and Soul Study.
AB  - BACKGROUND: Menopause is associated with urine phosphorus retention, which is
      mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone
      originating from bone that regulates urine phosphorus excretion. Whether sex or
      estrogen therapy is associated with different FGF-23 levels is unknown. STUDY
      DESIGN & SETTING: Cross-sectional study of ambulatory individuals with prevalent
      cardiovascular disease. PREDICTORS: Sex and, in women, use or nonuse of estrogen.
      OUTCOMES: Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to
      glomerular filtration rate (TMP/GFR), and plasma FGF-23 concentrations. RESULTS:
      For 987 participants, mean age was 67 +/- 11 years, 182 (18%) were women, and 46
      (25%) were using estrogen. Mean estimated GFR was 71 +/- 23 (SD) mL/min/1.73
      m(2). Compared with women who were not using estrogen, both women on estrogen
      therapy and men had significantly lower serum phosphorus concentrations, lower
      TMP/GFR values (indicating higher urine phosphorus excretion), and lower FGF-23
      concentrations with adjustment for age, demographics, and kidney function (P <
      0.001 for each). Mean FGF-23 levels were 68.7 (95% CI, 59.7-79.0) relative units
      (RU)/mL in non-estrogen-using women, 43.8 (95% CI, 41.2-46.5) RU/mL in men, and
      45.1 (95% CI, 35.2-57.4) RU/mL in women using estrogen in adjusted analysis (P <
      0.001). LIMITATIONS: Most participants were men. Estrogen therapy was not
      randomly assigned. CONCLUSIONS: Older women who are not using estrogen have
      higher FGF-23 levels than either men or women using estrogen. In the context of
      prior literature, these data suggest that postmenopausal phosphorus retention may
      stimulate higher FGF-23 concentrations after menopause.

PMID- 21855189
TI  - Diagnostic test studies in nephrology: quantity, quality, and scope.
AB  - BACKGROUND: Diagnostic errors represent an important cause of preventable harm in
      health care that may be reduced through evidence-based choice, use, and
      interpretation of diagnostic tests. We hypothesized that diagnostic errors are
      reduced through evidence-based choice, use, and interpretation of diagnostic
      tests. STUDY DESIGN: Retrospective cohort study. SETTING & POPULATION: Diagnostic
      test studies. SELECTION CRITERIA FOR STUDIES: Publications from 1966-2008
      retrieved from MEDLINE. INTERVENTION: The Quality of Diagnostic Accuracy Studies
      (QUADAS) tool. OUTCOMES: Number and coverage of diagnostic studies in nephrology
      and methodological quality of the test accuracy subset. RESULTS: Fewer diagnostic
      studies were published in nephrology than other areas of internal medicine,
      although the proportion of total citations that were diagnostic studies (4.9% +/-
      2.8% [SD]) was not statistically different from other specialties (P = 0.2).
      Within nephrology, some topic areas (eg, urinary tract infections) were over
      represented, whereas others (eg, acute kidney injury) had relatively few
      diagnostic studies (range, 2.7%-12.5%). Examining the randomly selected subset of
      studies that were diagnostic test accuracy studies (120) showed variable quality.
      Ninety-seven percent (116 of 120) of studies adequately described index test
      procedure, but only 27% (32 of 120) adequately blinded investigators to results
      of index tests, and 36% (43 of 120), to results of reference tests. The quality
      of nephrology diagnostic test accuracy studies has not improved substantially
      during the past 30 years. LIMITATIONS: Comparing nephrology with other
      specialties, some potential inequalities of scale could not be addressed, which
      may influence research output results across specialties. CONCLUSIONS: Diagnostic
      research in nephrology is published less frequently than most other medical
      specialties. The quality of diagnostic test accuracy studies that are published
      is variable and leaves room for improvement.

PMID- 21855190
TI  - Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
      cystatin C equations for estimating GFR with standardized serum cystatin C
      values.

PMID- 21855191
TI  - Maternal health and knowledge and infant health outcomes in the Ariaal people of
      northern Kenya.
AB  - There is a strong link between maternal knowledge and child well-being in many
      populations worldwide. Fewer studies have investigated the links between
      indigenous systems of medical knowledge and infant outcomes in non-Western
      societies, such as the Ariaal people of northern Kenya. This study has four
      goals. First, it defines culture-specific domains of health knowledge in Ariaal
      mothers using the cultural consensus method, a statistical model that measures
      knowledge shared by a set of informants. Second, it identifies factors that
      predict maternal health knowledge. Third, it investigates associations between
      maternal health knowledge and treatment-seeking behaviors. Finally, it associates
      health knowledge with biomarkers of infant health. Data collection took place in
      two separate periods. The first data collection period (October-November 2007)
      enrolled 41 women to participate in an open-ended interview or true-false
      consensus questionnaire. The second data collection period (November 2008-January
      2009) used information from the cultural consensus analysis to assess how health
      knowledge impacted infant health outcomes and treatment. Women and infants in
      this data collection period (n = 251 pairs) underwent anthropometric measurement
      and participated in a questionnaire that included traditional medicine consensus
      questions. Data were analyzed using the cultural consensus capabilities in
      ANTHROPAC 4.98; univariate and multivariate statistics were performed in SAS 9.2.
      This study found consensus in the domains of infant illness, traditional
      medicine, Western medicine, and treatment decision-making. Proximity to a medical
      dispensary and use of public health infrastructure significantly predicted higher
      levels of maternal health knowledge. Mothers' knowledge of traditional medicine
      was positively associated with treating infants at a dispensary versus at home.
      Finally, women with greater knowledge of traditional medicine had infants who
      were significantly less likely to have been ill in the previous month. These
      results highlight the importance of both traditional and Western health knowledge
      for Ariaal mothers and infants.

PMID- 21855192
TI  - How surgeons design treatment recommendations in orthopaedic surgery.
AB  - This paper examines how orthopaedic surgeons skilfully design treatment
      recommendations to display awareness of what individual patients are anticipating
      or seeking, and suggests limits to those efforts. It adds leverage to our
      parallel work by demonstrating that even when surgeons incorporate considerations
      of recipient design to 'fit' recommendations to patients' displayed orientations,
      an asymmetry between recommendations for vs. not for surgery remains:
      recommendations for surgery are generally proposed early, in relatively simple
      and unmitigated form, and as stand-alone options. In contrast, recommendations
      not for surgery tend to be significantly more complex: they are likely to be
      delayed, conveyed indirectly, mitigated and justified, and include other possible
      treatment options. These findings suggest a tension between surgeons' efforts to
      design recommendations for specific recipients and an overarching institutional
      bias favoring surgery. Surgeons' efforts to anticipate and respond to resistance
      to recommendations demonstrate a similar pattern: the methods used to counter
      patient resistance, and the sequential placement of those efforts, depends on
      whether the recommendation is for surgery or another treatment option. This work
      contributes to an understanding of treatment recommendations generally by showing
      how patients are co-implicated in their accomplishment: because surgeons
      incorporate considerations of recipient design in response to information
      provided explicitly or tacitly by patients, patients influence the rendering of
      recommendations from the beginning.

PMID- 21855193
TI  - Does country influence the health burden of informal care? An international
      comparison between Belgium and Great Britain.
AB  - The aim of this paper is to determine whether the association between the
      provision of informal care and the health status of caregivers is affected by the
      country of residence. We focus on two European countries, Belgium and Great
      Britain, and develop a methodology, which consists of matching a subset of areas
      from Britain with areas in Belgium that are demographically and socioeconomically
      similar. These pairs of areas are then used as fixed effects in logistic
      regressions of poor health. This allows us to take into account the influence of
      area type on health and to remove the influence of these local contextual
      characteristics from the estimated country effects. Results suggest that,
      although caregiving is more prevalent in Britain, the health burden associated
      with heavy caregiving activities is lower in Britain than in Belgium. This may be
      explained by the better targeting of long-term home care policies towards more
      severely dependent patients in Britain than in Belgium.

PMID- 21855194
TI  - Tophaceuos calcium pyrophosphate dihydrate deposition disease of the
      temporomandibular joint: the preferential site?

PMID- 21855195
TI  - Reduction malarplasty using modified L-shaped osteotomy.

PMID- 21855196
TI  - Primary and secondary telegnathic maxillomandibular advancement, with or without
      adjunctive procedures, for obstructive sleep apnea in adults: a literature review
      and treatment recommendations.
AB  - PURPOSE: To further define the role, surgical principles, and therapeutic
      efficacy of primary and secondary maxillomandibular advancement (MMA), with and
      without intrapharyngeal or extrapharyngeal adjunctive procedures, for obstructive
      sleep apnea in adults. MATERIALS AND METHODS: A review of the literature, using
      mean percent reduction in apnea hypopnea index as the primary outcome measure of
      therapeutic efficacy for standardized comparison. Other occasionally reported MMA
      outcome parameters were sleep staging variables, lowest oxyhemoglobin saturation
      levels, Epworth scores, blood pressure changes, lateral cephalometric data, and
      complications. RESULTS: Mean percent reduction in apnea hypopnea index was 92.1%
      for primary MMA with extrapharyngeal procedures, 88.4% for primary MMA, 86.6% for
      secondary MMA, 79.4% for primary MMA with intrapharyngeal procedures, 53.0% for
      non-MMA multilevel surgery, 31.3% for uvulopalatopharyngoplasty, and 89.8% for
      nasal continuous positive airway pressure. Treatment recommendations for
      telegnathic MMA included surgical goals and guidelines, indications and staging
      protocols, surgical principles and techniques, and postoperative airway
      management. CONCLUSIONS: Primary and secondary MMA are highly therapeutic, and
      extrapharyngeal are more therapeutic than intrapharyngeal procedures when
      performed concomitantly with primary MMA. However, long-term success of
      obstructive sleep apnea treatment should be measured by a yet undefined
      comprehensive algorithm of standardized multiple weighted outcome parameters.

PMID- 21855197
TI  - Evaluation of location and dimensions of lingual foramina using limited cone-beam
      computed tomography.
AB  - PURPOSE: To assess retrospectively the frequency and location of mandibular
      lingual foramina and their bony canals with limited cone-beam computed
      tomography. PATIENTS AND METHODS: Of 389 consecutively taken cone-beam computed
      tomograms of the mandible, 191 fulfilled the inclusion criteria of adequate
      quality, dentate areas within the region of interest, and visualization of the
      mandibular inferior border. Foramina were located according to tooth areas and
      were grouped into midline, paramedian, and posterior foramina. Linear
      measurements included vertical and horizontal diameters of the foramen and its
      distance to the lower border of the mandible. In addition, the frequency of bony
      canals originating from lingual foramina was calculated, and the course and
      anastomoses with other anatomic structures were assessed. RESULTS: In total, 217
      lingual foramina were detected in 1,054 sites. The midline of the symphysis had
      the highest frequency of foramina (96.2%), with the right first premolar area
      having the second highest frequency (27.5%). The mean diameter of lingual
      foramina ranged from 0.97 to 1.20 mm (horizontal diameter) and from 0.90 to 1.01
      mm (vertical diameter). Sizes differed significantly between midline and
      posterior foramina. The mean distance from the foramen to the inferior mandibular
      border varied from 7.07 to 11.54 mm, with extreme outliers in all 3 groups.
      Overall, 95.4% of lingual foramina presented with a bony canal originating from
      the lingual surface, and 40.1% of these canals communicated with other anatomic
      structures, most frequently with the incisive canal. CONCLUSIONS: Mandibular
      lingual foramina and bony canals are frequently present and should be included in
      presurgical radiographic diagnostics.

PMID- 21855198
TI  - Suppurative arthritis of the temporomandibular joint associated with
      bisphosphonate: a case report.

PMID- 21855199
TI  - Panoramic radiographs of head and neck cancer patients are often evidence of
      carotid artery atherosclerotic lesions: a sign of high-risk comorbid illness.
AB  - PURPOSE: The purpose of this study was to estimate the prevalence and identify
      the risk factors for calcified carotid artery plaque (CCAP) in patients with
      squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: Radiographs
      of 48 consecutive patients were evaluated for CCAP and their medical histories
      reviewed for the anatomic extent of cancer (staging) and atherogenic risk factors
      (age, extent of alcohol and tobacco use, body mass index, hypertension,
      dyslipidemia, and diabetes mellitus). RESULTS: Unilateral or bilateral CCAPs were
      found in 52.1% of subjects (mean age, 61.5 years). Hypertension was seen in a
      larger percentage (60%; P = .049) of subjects with CCAP on their radiographs
      compared with those without CCAP (30.4%). No other atheroma risk factors or stage
      of cancer differed significantly between those with and those without CCAP.
      CONCLUSION: Panoramic radiographs of patients with squamous cell carcinoma of the
      head and neck show a very high rate of CCAP, a marker of comorbid vascular
      diseases that may cause treatment complications and affect overall survival.

PMID- 21855200
TI  - Peer victimization, depressive symptoms, and high salivary cortisol predict
      poorer memory in children.
AB  - The predictive relations of peer victimization, depressive symptoms, and salivary
      cortisol on memory in 168 children aged 12 at Time 1 (T1) were examined using a
      longitudinal design in which data were collected on four occasions over a 2-year
      period. Results indicated that: (1) peer victimization, depressive symptoms, and
      evening cortisol were stable over time, (2) peer victimization and elevated
      symptoms of depression were concurrently linked at each time, (3) T1 peer
      victimization predicted elevated symptoms of depression at T2 which in turn
      predicted lower cortisol levels at T3, and (4) controlling for earlier
      associations, T3 peer victimization, depressive symptoms, and higher morning and
      evening cortisol levels uniquely predicted memory deficits at T4. The links
      between elevated cortisol, symptoms of depression, and poor memory are consistent
      with published research on depressed adults and extend the findings to children
      exposed to peer victimization. These findings highlight that peer abuse is
      harmful and may impact children's long-term mental health and memory functioning.

PMID- 21855201
TI  - Psychopathy and indirect aggression: the roles of cortisol, sex, and type of
      psychopathy.
AB  - Salivary cortisol was examined in relation to indirect aggression and primary
      psychopathy (i.e., cold affect and interpersonal manipulation) and secondary
      psychopathy (i.e., criminal tendencies and erratic lifestyle) in a sample of 154
      undergraduate students. Results revealed that although psychopathy and indirect
      aggression were strongly correlated, when statistically controlling for each of
      type of psychopathy, only primary psychopathy was related to indirect aggression.
      In women but not in men, lower cortisol was associated with higher levels of
      primary psychopathy and higher cortisol was associated with higher levels of
      secondary psychopathy. Cortisol was not related to indirect aggression. Results
      are discussed from both an evolutionary and developmental perspective.

PMID- 21855202
TI  - Experience with intravenous immunoglobulin in severe childhood atopic dermatitis.

PMID- 21855203
TI  - Mesenchymal stem cells originating from ES cells show high telomerase activity
      and therapeutic benefits.
AB  - We establish a novel method for the induction and collection of mesenchymal stem
      cells using a typical cell surface marker, CD105, through adipogenesis from mouse
      ES cells. ES cells were cultured in a medium for adipogenesis. Mesenchymal stem
      cells from mouse ES cells were easily identified by the expression of CD105, and
      were isolated and differentiated into multiple mesenchymal cell types.
      Mesenchymal stem cells showed remarkable telomerase activity and sustained their
      growth for a long time with a high potential for differentiation involving
      skeletal myogenesis in vitro. When mesenchymal stem cells were transplanted into
      the injured tibialis anterior muscles, they differentiated into skeletal muscle
      cells in vivo. In addition, they improved the vascular formation, but never
      formed teratoma for longer than 6 months. Gene expression profiles revealed that
      mesenchymal stem cells lost pluripotency, while they acquired high potential to
      differentiate into mesenchymal cell lines. They thus indicate a promising new
      source of cell-based therapy without teratoma formation.

PMID- 21855204
TI  - Synthetic vaginal tapes for stress incontinence: proposals for improved
      regulation of new devices in Europe.

PMID- 21855205
TI  - Re: Nicolas Mottet, Joaquim Bellmunt, Michel Bolla, et al. EAU guidelines on
      prostate cancer. Part II: Treatment of advanced, relapsing, and castration
      resistant prostate cancer. Eur Urol 2011;59:572-83.

PMID- 21855206
TI  - Low-dose-rate brachytherapy, radical prostatectomy, or external-beam radiation
      therapy for localised prostate carcinoma: the growing dilemma.

PMID- 21855207
TI  - Standard or extended lymphadenectomy in radical cystectomy: what metric of
      surgical quality for lymph node dissections matters in improving patient
      outcomes?

PMID- 21855208
TI  - Improved toxicity profile following high-dose postprostatectomy salvage radiation
      therapy with intensity-modulated radiation therapy.
AB  - BACKGROUND: With salvage radiation therapy (SRT) in the postprostatectomy
      setting, the need to deliver sufficient radiation doses to achieve a high
      probability of tumor control is balanced with the risk of increased toxicity.
      Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage
      setting is gaining interest as a treatment strategy. OBJECTIVE: Compare acute and
      late toxicities in patients treated with IMRT and three-dimensional conformal
      radiation therapy (3D-CRT) in the postprostatectomy salvage setting. DESIGN,
      SETTING, AND PARTICIPANTS: A total of 285 patients who were treated at our
      institution between 1988 and 2007 with SRT after radical prostatectomy for
      biochemical recurrence were identified. All medical records were reviewed and
      toxicity recorded. Median follow-up was 60 mo. INTERVENTION: All patients were
      treated with SRT with either 3D-CRT (n=109) or IMRT (n=176). A total of 205
      patients (72%) were treated with doses >=70Gy. MEASUREMENTS: Late
      gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the
      Common Terminology Criteria for Adverse Events v. 3.0 definition. RESULTS AND
      LIMITATIONS: The 5-yr actuarial rates of late grade >=2 GI and GU toxicity were
      5.2% and 17.0%, respectively. IMRT was independently associated with a reduction
      in grade >=2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT,
      10.2%; p=0.02). IMRT was not associated with a reduction in risk of grade >=2 GU
      toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p=0.86), urinary incontinence (5
      yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p=0.25), or grade 3 erectile dysfunction (5-yr
      IMRT, 26%; 5-yr 3D-CRT, 30%; p=0.82). Of patients who developed late grade >=2 GI
      or GU toxicity, 38% and 44%, respectively, experienced resolution of their
      symptoms prior to the last follow-up. CONCLUSIONS: Our experience with high-dose
      IMRT in the postprostatectomy salvage setting demonstrates that the treatment can
      be delivered safely with an associated reduction in late GI toxicity.

PMID- 21855209
TI  - Minimal clinically important differences in the erectile function domain of the
      International Index of Erectile Function scale.
AB  - BACKGROUND: Despite widespread adoption of the six-item erectile function (EF)
      domain of the International Index of Erectile Function (IIEF) as a clinical trial
      end point, there are currently no objective data on what constitutes a minimal
      clinically important difference (MCID) in the EF domain. OBJECTIVE: Estimate the
      MCID for the IIEF EF domain. DESIGN, SETTING, AND PARTICIPANTS: Anchor-based
      MCIDs were estimated using data from 17 randomized, double-blind, placebo
      controlled, parallel-group clinical trials of the phosphodiesterase type 5
      inhibitor (PDE5-I) tadalafil for 3345 patients treated for 12 wk. MEASUREMENTS:
      The anchor for the MCID is the minimal improvement measure calculated using
      change from baseline to 12 wk on IIEF question 7: "Over the past 4 weeks, when
      you attempted sexual intercourse how often was it satisfactory for you?" MCIDs
      were developed using analysis of variance (ANOVA)- and receiver operating
      characteristic (ROC)-based methods in a subset of studies (n=11) by comparing
      patients with and without minimal improvement (n=863). MCIDs were validated in
      the remaining six studies (n=377). RESULTS AND LIMITATIONS: The ROC-based MCID
      for the EF domain was 4, with estimated sensitivity and specificity of 0.74 and
      0.73, respectively. MCIDs varied significantly (p<0.0001) according to baseline
      ED severity (mild: 2; moderate: 5; severe: 7). MCIDs consistently distinguished
      between patients in the validation sample classified as no change or minimally
      improved overall and by geographic region, ED etiology, and age group. MCIDs did
      not differ by age group, geographic region, or ED etiology. Current analyses were
      based on 17 clinical trials of tadalafil. Results need to be replicated in
      studies using other PDE5-Is or in nonpharmacologic intervention studies.
      CONCLUSIONS: The contextualization of treatment-related changes in terms of
      clinically relevant improvement is essential to understanding treatment efficacy,
      to interpreting results across studies, and to managing patients effectively.
      This analysis provides, for the first time, anchor-based estimates of MCIDs in
      the EF domain score of the IIEF.

PMID- 21855210
TI  - Re: Markus J. Bader, Christian Gratzke, Michael Seitz, et al. The "all-seeing
      needle": initial results of an optical puncture system confirming access in
      percutaneous nephrolithotomy. Eur Urol 2011;59:1054-9.

PMID- 21855211
TI  - Physical activity, obesity, and lower urinary tract symptoms.

PMID- 21855212
TI  - An easy diagnostic tool distinguishing lateral medullary infarction from
      peripheral vertigo.

PMID- 21855213
TI  - An unusual focal leg dystonia in descending stairs responsive to anticonvulsants.

PMID- 21855214
TI  - Development of adsorbent from Teflon waste by radiation induced grafting:
      equilibrium and kinetic adsorption of dyes.
AB  - Mutual radiation grafting technique was employed to graft polyacrylic acid (PAA)
      onto Polytetrafluoroethylene (Teflon) scrap using high energy gamma radiation.
      Polyacrylic acid-g-Teflon (PAA-g-Teflon) adsorbent was characterized by grafting
      extent measurement, FTIR spectroscopy, SEM and wet ability & surface energy
      analysis. The PAA-g-Teflon adsorbent was studied for dye adsorption from aqueous
      solution of basic dyes, namely, Basic red 29 (BR29) and Basic yellow 11 (BY11).
      The equilibrium adsorption data were analyzed by Langmuir and Freundlich
      adsorption isotherm models, whereas, adsorption kinetics was analyzed using
      pseudo-first order, pseudo-second order and intra-particle diffusion kinetic
      models. Equilibrium adsorption of BR29 was better explained by Langmuir
      adsorption model, while that of BY11 by Freundlich adsorption model. The
      adsorption capacity for BY11 was more than for BR29. Separation factor (R(L)) was
      found to be in the range 0 < R(L) < 1, indicating favorable adsorption of dyes.
      Higher coefficient of determination (r(2) > 0.99) and better agreement between
      the q(e,cal) and q(e,exp) values suggested that pseudo-second order kinetic model
      better represents the kinetic adsorption data. The non-linearity obtained for
      intra-particle diffusion plot indicated, more than one process is involved in the
      adsorption of basic dyes. The desorption studies showed that ~95% of the adsorbed
      dye could be eluted in suitable eluent.

PMID- 21855215
TI  - Tail-end Hg capture on Au/carbon-monolith regenerable sorbents.
AB  - In this work, a regenerable sorbent for Hg retention based on carbon supported Au
      nanoparticles has been developed and tested. Honeycomb structures were chosen in
      order to avoid pressure drop and particle entrainment in a fixed bed. Carbon
      based supports were selected in order to easily modify the surface chemistry to
      favour the Au dispersion. Results of Hg retention and regeneration were obtained
      in a bench scale experimental installation working at high space velocities (for
      sorbent, 53,000 h(-1); for active phase, 2.6 * 10(8) h(-1)), 120  degrees C for
      retention temperature and Hg inlet concentration of 23 ppbv. Gold nanoparticles
      were shown to be the active phase for mercury capture through an amalgamating
      mechanism. The mercury captured by the spent sorbent can be easily released to be
      disposed or reused. Mercury evolution from spent sorbents was followed by TPD
      experiments showing that the sorbent can be regenerated at temperatures as low as
      220  degrees C.

PMID- 21855216
TI  - Changes in the inositol lipid signal system and effects on the secretion of TNF
      alpha by macrophages in severely scalded mice.
AB  - AIM: In order to study the mechanism of abnormal macrophage (Mphi) function in
      pro-inflammatory cytokine changes after burn, the inositol lipid signal system
      and its role in tumour necrosis factor-alpha (TNF-alpha) secretion by peritoneal
      Mphis was observed in severely scalded mice. METHODS: Eighteen percent total body
      surface area (TBSA) full-thickness scalded mice were used as animal model in this
      experiment. Peritoneal Mphis stimulated by lipopolysaccharide in vitro were
      collected at different time intervals (0, 2, 6, 12, 24 and 48 after burn hour
      (PBH)), The activities of phosphatidylinositol-phospholipase C (PI-PLC), inositol
      1, 4,5, -triphosphate (IP(3)), protein kinase C (PKC), diacylglycerol (DAG) and
      TNF-alpha and the level of Ca(2+) concentration in peritoneal Mphis were
      measured, and the effects of specific PKC inhibitor H-7 and calmodulin antagonist
      W-7 on the production of TNF-alpha were also observed. RESULTS: After scald,
      increased activities of TNF-alpha and PLC of Mphi were observed and peaked at 12
      PBH. The activities of DAG and IP(3) and the concentration of Ca(2+) were
      markedly increased and reached their peaks at 24 PBH simultaneously. Membrane PKC
      activity was up-regulated after scald and showed a positive correlation with the
      change of DAG (r=0.83, P<0.05). There was also positive correlation between IP(3)
      and Ca(2+) activity (r=0.946, P<0.01). When 12 PBH was chosen as the time point
      for in vitro intervention with the pre-treatment by H-7, both membrane PKC and
      TNF-alpha activity decreased significantly. There was no obvious change of TNF
      alpha activity with the application of W-7. CONCLUSIONS: These results indicated
      that the abnormal activity of TNF-alpha of Mphis might be regulated by the
      inositol lipid signal system following severe burn. The DAG-PKC signal pathway
      showed closer relationship than IP(3)-Ca(2+) in TNF-alpha production and could be
      the optimal target in the prevention and treatment of the systemic inflammatory
      response syndrome.

PMID- 21855217
TI  - Deep foot burns: effects of early excision and grafting.
AB  - Few on the problem of foot burns can be found in the available scientific
      literature. It is necessary to mention that often deep foot burns occur in
      Central Asia since many natives still use the ancient means of heating called
      'Sandal' during the winter months. Eighty-four patients with severe foot burns
      were treated in the Burn department of RCSUMA and the Inter-regional Burn Center,
      Uzbekistan. The patients were subdivided into two groups, depending upon the
      terms of performing operative intervention. There was no special allocation of
      patients to groups. Criteria for selection were isolated deep burns of the foot.
      As for the character of the injury, area of deep burn and the severity of injury,
      patients of the control and basic groups were not different. The first group
      included 34 patients on whom early excision was done using skin graft 4-5 days
      after resuscitation, and the second group consisted of 50 patients who were
      treated in the traditional way. Methods used on the first group, described in
      this article, helped to improve the general condition of patients, contributed to
      the restoration of their foot function, lessened joint deformities and post-burn
      contracture deformities, shortened their stay in hospital and also reduced
      expenses.

PMID- 21855218
TI  - The correlation of in vivo burn scar contraction with the level of alpha-smooth
      muscle actin expression.
AB  - This study describes the direct association of in vivo burn scar contraction with
      the level of alpha-smooth muscle actin (alpha-SMA) in scar tissue, in a porcine
      burn model. The expression of alpha-SMA was investigated in 100 biopsies from 44
      6-week old burn scars and in 85 biopsies from 16 2-week old burn wounds.
      Statistical analysis showed that the levels of alpha-SMA in 6-week old scars were
      significantly negatively correlated to scar size (r=-0.68) and the higher levels
      of alpha-SMA were observed in smaller scars. Moreover, alpha-SMA was also found
      to be significantly positively correlated to re-epithelialisation time (r=0.57)
      and scar thickness (r=0.58) and higher levels of alpha-SMA were detected in
      thicker scars with delayed wound closure. Further statistical analysis revealed
      that scar contraction can be explained best by the level of alpha-SMA expression
      and partially by scar thickness. Other variables, such as different dressings and
      individual pig, may also partly contribute to scar contraction. At week 2 after
      burn, the level of alpha-SMA expression in 16 burn wounds was significantly
      related to the depth of burns and wound healing outcome. To our knowledge, this
      is the first study to provide in vivo evidence of the association of alpha-SMA
      expression with scar contraction, scar thickness, re-epithelialisation time and
      the depth of burn in a large animal burn model with scars similar to human
      hypertrophic scar.

PMID- 21855219
TI  - Epidemiology of fatal burns in rural South Africa: a mortuary register-based
      study from Mpumalanga Province.
AB  - AIM: The study investigates the epidemiology of fatal burns in the predominantly
      rural province of Mpumalanga, South Africa. METHOD: The study is cross-sectional
      and investigates region specific data extracted from a National Injury Mortality
      Surveillance System (NIMSS) and originally gathered at mortuaries. Fatal burns
      sustained during the 2 year period 2007 and 2008 are analysed (n=304 cases).
      Mortality rates by age group, sex and district were compiled and attention was
      paid to manner of death, location, and temporal characteristics (time of day,
      weekday, season). RESULTS: The overall fatal burn rate was 3.8 per 100,000
      inhabitants (95% CI 3.4-4.3). The highest rates were among the oldest age group
      (8.2/100,000; 95% CI 6.1-10.7), males (5.3/100,000; 95% CI 4.6-6.2) and in one of
      the three districts, Nkangala (4.8/100,000; 95% CI 3.9-5.6). Most burns were
      accidental (68.4%) and intentional ones (13.5%) occurred in particular among
      older people and in the home. Burns were sustained frequently at home (55.6%),
      between midnight and 5a.m. and towards the end of the week. Seasonal variations
      were more pronounced in Nkangala. CONCLUSIONS: Fatal burns could be less common
      in rural than urban South Africa. As in urban South Africa, however, older
      people, young children, and males are more at risk. Not surprisingly, the
      occurrence of fatal burns is strongly related to living conditions and lifestyle,
      which vary even within rural areas of South Africa.

PMID- 21855220
TI  - Aesthetic and functional restoration of anterior neck scar contracture using a
      bipedicled expanded forehead flap.
AB  - OBJECTIVE: The study aimed to explore a new method to restore functional and
      cosmetic outcomes for anterior neck burn scar contracture. METHODS: Tissue
      expanders were implanted subcutaneously under the muscle of the forehead. Tissue
      expansion started 1 week postoperatively. When the skin expansion finished, a
      bilateral pedicled expanded skin flap was created on the basis of the superficial
      temporal artery and transferred to the anterior neck. Both the range of motion of
      cervical spine and the mental cervical angle were measured before and after
      operation. Data were analysed by Statistical Package for Social Sciences (SPSS)
      13.0 and t-test. RESULTS: From September 2006 to May 2010, six male patients were
      treated by this method. The active range of motion of the neck of patients
      improved, the postoperative ranges of active flexion, extension, left flexion,
      right flexion and left and right rotation of cervical spine increased
      respectively. The mental cervical angle was 152.7+/-1.9 degrees  preoperatively
      and 90.7+/-2.2 degrees  postoperatively; the physiological angle was recovered.
      Patients were followed up from 5 months to 3 years, they were satisfied with the
      results and no recurrence of contracture was found. CONCLUSION: The bipedicled
      expanded forehead flap, which provided good blood supply, repaired anterior
      contracture in the neck and created both aesthetic and functional results; it
      also diminished donor morbidity.

PMID- 21855222
TI  - Macrophages make me sick: how macrophage activation states influence sickness
      behavior.
AB  - The macrophage (MPhi) is an essential cellular first responder in the innate
      immune system, sensing, alerting, removing and destroying intrinsic and extrinsic
      pathogens. While congenital aplasia of granulocytes, T or B lymphocytes leads to
      serious disease, lack of MPhis is incompatible with life. The MPhi, however, is
      not a monomorphic entity. These constructers, repairers and defenders of the body
      are diverse in form and function. What controls MPhi phenotype is beginning to be
      understood and involves a complex interplay of origination, location and
      microenvironment. Common to all MPhi developmental pathways are pro-inflammatory
      and anti-inflammatory cytokines. MPhis respond to these bioactives in distinct
      ways developing recently recognized activation phenotypes that canonically
      support bacterial clearance (classical activation), parasite defense/tissue
      repair (alternative activation) and anti-inflammation (deactivation). Critically,
      the same cytokines which orchestrate immune defense and homeostasis dramatically
      impact sense of well being and cognition by eliciting sickness symptoms. Such
      behaviors are the manifestation of pro/anti-inflammatory cytokine action in the
      brain and are a direct consequence of MPhi function. This review describes the
      "new" archetypal MPhi activation states, delineates microglia phenotypic
      plasticity and explores the importance of these macrophage activation states to
      sickness behavior.

PMID- 21855223
TI  - Contrasting behavioral effects of acute nicotine and chronic smoking in
      detoxified alcoholics.
AB  - BACKGROUND: Current literature suggests that acute nicotine administration
      provides a compensatory mechanism by which alcoholics might alleviate attentional
      deficits. In contrast, chronic smoking is increasingly recognized as negatively
      affecting neurobehavioral integrity. These opposing effects have not been
      simultaneously examined. Thus, we sought to a) extend previous work by exploring
      the effects of acute nicotine effects on vigilance components of attention and
      replicate previous findings suggesting that treatment-seeking alcoholics
      experience benefit to a greater extent than do other groups; and b) to examine
      the impact of chronic smoking on these tasks and across subgroups. METHODS:
      Substance abusing participants (N=86) were recruited and subgrouped on the basis
      of dependency criteria as either alcoholics, alcoholics with co-morbid stimulant
      dependence, or stimulant dependent individuals. Groups of cigarette-smoking
      (N=17) and non-smoking (N=22) community controls were recruited as comparison
      groups. Smoking subjects were assigned a placebo, low, or high dose nicotine
      patch in a double-blind placebo controlled fashion. Non-smoking controls were
      administered either a placebo or low dose. Testing occurred after dose
      stabilization. RESULTS: General linear models indicated greater sensitivity to
      acute nicotine administration among alcoholics than other groups when controlling
      for the effect of intensity of smoking history, as reflected by pack-years. Pack
      years correlated negatively with performance measures in alcoholics but not
      stimulant abusing subgroups or smoking controls. Finally, regression analyses
      demonstrated that pack-years predicted poorer performance only for the alcoholic
      subgroup. CONCLUSIONS: These results support previous work finding a compensatory
      effect of acute nicotine administration on attentional performance in alcoholics
      and reinforce the consideration of recent nicotine use as a confound in
      neurocognitive studies of alcoholics. Of particular interest is the finding that
      smoking history as reflected in pack-years predicted poorer performance, but only
      among alcoholics. Further systematic study of these opposing effects among
      alcoholics and other groups using a broader array of tasks is needed.

PMID- 21855224
TI  - College students' evaluations of alcohol consequences as positive and negative.
AB  - Alcohol expectancy, motivation, and consequences measures assume a known valence
      of 'positive' and 'negative' outcomes. However, different individuals may rate
      the same consequences of alcohol use as good or bad. The current study examines
      the extent to which: (a) college students rate researcher-defined positive
      consequences as good and researcher-defined negative consequences as bad, and (b)
      these evaluations predict alcohol use and problems after controlling for previous
      use. In longitudinal self-reports via web-surveys across the first three
      semesters of college, students (N=600; 54% women) reported their alcohol use and
      problems, experienced consequences, and evaluations of those consequences.
      Contrary to the generally-accepted valence of positive consequences, Fun/Social
      consequences were viewed as neutral or negative by 22% (having more fun) to 73%
      (relieving boredom) of participants. Over half of participants evaluated each of
      the Relaxation, Sex, and Image consequences items as neutral or negative.
      Consistent with the generally-accepted valence of negative consequences,
      Physical/Behavioral consequences were viewed by the majority as negative,
      although 11% (getting in trouble with police/authorities) to 34% (doing/saying
      something embarrassing) of students rated these consequences as neutral or
      positive. Independent of levels of previous drinking, more positive evaluations
      of Fun/Social consequences prospectively predicted frequency, quantity, and
      maximum drinks. Less negative evaluations of Physical/Behavioral consequences
      predicted more alcohol problems. There is variation in the evaluations of
      consequences among college students, and understanding characteristics of those
      who view consequences as positive or negative may have implications for future
      alcohol-related behaviors and problems.

PMID- 21855225
TI  - Correlates of perceiving a need for treatment among adults with substance use
      disorder: results from a national survey.
AB  - Although millions of adults meet criteria for substance use disorder (SUD) in the
      U.S., only a fraction receive treatment. This may be due to individuals with SUD
      not perceiving a need for treatment. In order to distinguish persons with SUD who
      perceive a need for treatment from those who do not, correlates for the perceived
      need for treatment were assessed for respondents with alcohol use disorder only,
      drug use disorder only and both alcohol and drug use disorder. Data were from the
      combined 2005-2009 datasets of the National Survey on Drug Use and Health.
      Logistic regression models were used to calculate odds ratio and 95% confidence
      intervals. Results demonstrated that among respondents who need treatment but did
      not receive treatment for alcohol use disorder, drug use disorder and both
      alcohol and drug use disorders, 3.3%, 8.3% and 12.4% perceived a need for
      treatment, respectively. No single socio-demographic correlate was predictive of
      perceiving a need across the three subpopulations suggesting that screenings for
      substance use disorder should be done in a setting where the general population
      may be accessed, e.g. primary care settings. Correlates associated with
      perceiving a need for treatment for all three subpopulations included
      psychological distress, disorder severity and substance type. Although
      respondents with greater disorder severity were more likely to perceive a need
      for treatment, a large proportion of those still do not perceive a need for
      treatment. Screening and brief interventions would facilitate treatment entry
      among those with the most severe disorders.

PMID- 21855226
TI  - Further support for vitamin D supplement in delaying the progression of ALS.

PMID- 21855221
TI  - Regulation of corticoid and serotonin receptor brain system following early life
      exposure of glucocorticoids: long term implications for the neurobiology of mood.
AB  - Potent glucocorticoids (GC) administered early in life have improved premature
      infant survival dramatically. However, these agents may increase the risk for
      physical, neurological and behavior alterations. Anxiety, depression and
      attention difficulties are commonly described in adolescent and young adult
      survivors of prematurity. In the present study we administered vehicle,
      dexamethasone, or hydrocortisone to Sprague-Dawley rat pups on postnatal days 5
      and 6, mimicking a short term clinical protocol commonly used in human infants.
      Two systems that are implicated in the regulation of stress and behavior were
      assessed: the limbic-hypothalamic-pituitary-adrenal axis [LHPA; glucocorticoid
      and mineralocorticoid receptors within] and the Serotonin (5-HT) system. We found
      that as adults, male Sprague-Dawley pups treated with GC showed agent specific
      altered growth, anxiety-related behavior, changes in corticoid response to
      novelty and gene expression changes within LHPA and 5-HT-related circuitry. The
      data suggest that prolonged GC-receptor stimulation during the early neonatal
      period can contribute to the development of individual differences in stress
      response and anxiety-related behavior later in life.

PMID- 21855228
TI  - Induction the cornification of squamous cancerous cells to eliminate tumor cells
      by promotion cell differentiation and stratum.
AB  - Cornification is a kind of apoptosis of squamous epithelial cell in the upper
      layer of the epithelial tissue. The basal cells away from cell-cycle embark on
      terminal differentiation, stratum, then die by apoptosis. The critical elements
      interference from the normal differentiation of squamous cells will lead to cell
      malignant transformation. We would like to put forward a hypothesis that
      initiation the cornification of squamous cancerous cells by promotion cell
      differentiation and stratum can promote squamous carcinoma cells death. Attempts
      of induction squamous cancerous cells terminal differentiation will add to our
      understanding of the connection between keratinocytes cornification and the death
      of squamous-cell carcinoma.

PMID- 21855227
TI  - An hypothesis on pressure transmission from anterior chamber to optic nerve.
AB  - Few studies have characterized how pressure in the anterior chamber (AC) of the
      eye is transmitted via the vitreous to the vitreous-ganglion cell interface. We
      are aware of only one study that simultaneously measured the pressures in the AC
      and vitreous humor; and of only one study that simultaneously measured the
      pressures in the AC and the suprachoroidal space (SCS). The pressure in the AC is
      defined as the intraocular pressure (IOP), which when elevated beyond
      statistically normal limits is a recognized risk factor for glaucoma, a malady
      best described as an optic neuropathy with degeneration and eventual death of the
      retinal ganglion cells (GC's) and highly characteristic changes in the optic
      nerve head (ONH). Most investigators currently believe that the prevalent risk
      factor for GC apoptosis is ocular hypertension, but no one has demonstrated how
      an increase in IOP in the AC is transmitted to the GC's. In patients with primary
      open angle glaucoma, the pressure in the AC increases due to an increase in the
      resistance of the trabecular meshwork (TM) outflow pathway. We questioned how
      such increased pressure in the AC would be transmitted to the GC to produce the
      changes in the ONH seen in glaucoma. Based on our preliminary data and purview of
      the literature, we hypothesize that a pressure increase originating in the AC is
      likely transmitted via both the SCS and the vitreous, with transmission via the
      former pathway probably most efficient in affecting the GC. Independently of the
      mechanism that produces GC apoptosis, the ones that are first affected, as
      repeatedly shown by visual field tests, are the most peripheral ones; i.e., those
      whose axons are the most external as they form the ONH and enter the lamina
      cribrosa. There are no published reports explaining this peculiarity. The dogma
      is that the pressure transmitted via the vitreous is higher at the periphery
      because it is transmitted across a shorter distance, since the vitreous acts as a
      buffer that absorbs part of the pressure being transmitted. We propose that IOP
      is not only transmitted via the vitreous but also via the SCS. Increases in IOP
      could be efficiently applied via the SCS to the most external axons of the ONH as
      they leave the eye. Our hypothesis can also explain low-tension glaucoma in which
      the most peripheral GC's are also affected first, because pressure is transmitted
      without decay due to a reduced uveoscleral (UVS) flow.

PMID- 21855229
TI  - Are prostatitis symptoms associated with an isoprostane-mediated vicious circle?
AB  - Prostatitis is a disease that seriously affects the quality of patients' life. In
      the majority of cases, chronic prostatitis (chronic pelvic pain syndrome--CPPS)
      has an unclear pathogenesis. Anti-inflammatory and anti-infectious treatments
      have remained controversial. According to the latest research, prostatitis has
      been associated with oxidative stress (OxS) and/or OxS-related genetic
      polymorphisms. We have observed that prostatitis patients have systemic OxS in
      case of inflammation and pain. We propose a new explanation for the role of OxS
      in the pathogenesis of prostatitis and describe the putative OxS-related pathways
      in detail. The neural vicious circle starts by activation of primary sensory
      afferents. Glutamate mediates the signal to the neurons in the dorsal horn of the
      spinal cord, and facilitates calcium influx into their mitochondria. The latter
      causes an increased production of superoxide radicals. If the superoxide
      production is not effectively controlled by mitochondrial superoxide dismutase
      (Mn-SOD), then superoxide leads to OxS and lipid peroxidation. Consequent release
      of electrophilic lipid peroxidation products (LPP) from dorsal horn of the spinal
      cord causes pain by activating the primary sensory afferents, again. Additional
      LPP-mediated causes of pain include glutathione depletion and neuron
      sensitisation by isoprostanes. Excretion of LPP into urine may exert positive
      feedback as well. Currently, different information exists about chronic
      prostatitis (inflammation, pain, oxidative stress, neural sensitisation, lower
      urinary tract symptoms). The clear links between these data are actually absent.
      We propose that vicious circle based on LPP, especially isoprostanes, is the
      linking mechanism.

PMID- 21855230
TI  - The dopamine hypothesis of social support.
AB  - It has been suggested that dopamine may play an important role in human evolution
      and adaptive behaviors. Recent studies have revealed an association between the
      dopamine system and social support among healthy individuals. However, the
      underlying mechanism remains unclear. In the present study, we propose a dopamine
      hypothesis, which states that the level of dopaminergic system activity could
      influence social support via the capacity of cognitive function. Two lines of
      literature supporting the mechanism of this hypothesis are reviewed. Further
      experimental and longitudinal study is required to test this hypothesis. This
      hypothesis may help to identify the mechanism explaining the influence of
      dopamine on social support and provide support for dopaminergic pharmacotherapy
      for deficits in social behaviors.

PMID- 21855231
TI  - Startle response related genes.
AB  - The startle reaction (also known as the startle response, the startle reflex, or
      the alarm reaction) is the psychological and physiological response to a sudden
      unexpected stimulus, such as a flash of light, a loud noise (acoustic startle
      reflex), or a quick movement near the face. Abnormalities of startle response
      have been observed in many stress-related mental disorders, such as schizophrenia
      and post-traumatic stress disorder (PTSD). However, the molecular mechanisms of
      startle in stress-associated conditions--for example, whether the startle
      reaction is associated with any gene variance--is still unknown. In this paper,
      we will carry out a systematic review by retrieving, assessing, and combining,
      when applicable, individual studies investigating association of the molecular
      variation of candidate gene with the startle response. The systematic review is
      based on the search for numerous publications using the keywords "startle gene"
      on September 15, 2010 using PubMed, which comprises more than 20 million
      citations for biomedical literature from MEDLINE and life science journals. A
      total of 486 publications regarding genes associated with startle have been
      obtained and reviewed here. There are fewer than 20 publications associating
      genes with the startle response between 1979, when the first valuable paper was
      published, and 1999. However, publications have dramatically increase from 2001
      and reaches over 70 in 2009. We have characterized them into three categories:
      startle-associated gene studies in humans, in animals, as well as in both human
      and animals. This review of research strategy may provide the information for
      identifying a biomarker for startle response, with the objective of translating
      research into clinical utility: diagnosis and treatment of stress-induced mental
      disorders.

PMID- 21855232
TI  - ALK-positive extramedullary plasmacytoma with expression of the CLTC-ALK fusion
      transcript.
AB  - Anaplastic lymphoma kinase (ALK)-positive non-Hodgkin lymphoma (NHL) was long
      thought to be a disease occurring uniquely in T or null-cell lymphomas. More
      recently, however, a small number of B-lineage lymphomas have been reported to
      express ALK fusion genes. These tumors often exhibit a plasmablastic morphology,
      a finding which prompted our interest in looking for ALK fusions in plasma cell
      neoplasms. We studied 46 cases of extramedullary plasmacytoma by immunostaining
      with anti-ALK antibody and fluorescence in situ hybridization (FISH) analysis
      using an ALK break-apart probe and found one case to be ALK protein-positive and
      demonstrated the disruption of the ALK gene in this case. Immunohistochemistry
      showed that the tumor cells were strongly positive for CD138, VS38c, and
      epithelial membrane antigen, but lacked expression of CD20, CD79a, CD45, and
      CD30. Both RT-PCR and genomic DNA-PCR confirmed the CLTC-ALK fusion. This finding
      expands the lists of the ALK-positive tumors, and ALK-positive extramedullary
      plasmacytoma may benefit from the treatment of ALK inhibitor in the future.

PMID- 21855233
TI  - Prevention of anastomotic thrombosis by botulinum toxin B after acute injury in a
      rat model.
AB  - PURPOSE: Revascularized or replanted digits may fail because of vessel
      thrombosis. Off-label use of botulinum toxin type A injected subcutaneously has
      been used successfully in limited case series to treat vasospastic disorders.
      Botulinum toxin type B (BTX-B) is thought to have an earlier onset of action than
      type A in certain settings. We used a rat model to determine the ability of BTX-B
      to decrease vasospasm and prevent thrombosis after acute vessel division and
      anastomotic repair. METHODS: We transected and immediately repaired the bilateral
      femoral arteries and veins of 25 rats via microscopic technique. We measured each
      vessel's diameter before transection. Each rat had 1 leg randomly assigned to
      receive BTX-B; the contralateral side received normal saline. We separated the
      animals into 5 groups. Each group underwent vasospastic stress at a different
      time point (12, 24, 48, 72, and 120 h) after the anastomoses and treatment with
      BTX-B or saline. Vasospastic stress included a lower extremity cold temperature
      challenge and systemic treatment with phenylephrine. After vasospastic stress, we
      reopened the wounds and recorded vessel thrombosis and diameter. RESULTS: Vessel
      thrombosis rate was lower in the BTX-B-treated group of vessels compared with
      those receiving placebo. Thrombosis rate was 8% for BTX-B-treated arteries versus
      68% for saline-treated arteries. Thrombosis rate was 20% for BTX-B-treated veins
      versus 76% for saline-treated veins. Overall vessel thrombosis rate was
      significantly lower for BTX-B at all time points except at 120 hours when no
      thrombotic events occurred for either group. Average increase in diameter for BTX
      B-treated vessels was significantly greater than that for the controls regardless
      of patency. CONCLUSIONS: BTX-B prevented or reduced the incidence of thrombosis
      after acute vessel anastomosis in this rat model at all time points less than 120
      hours compared with placebo. The average final vessel diameter throughout the
      series of BTX-B-treated vessels was significantly larger than in the control
      group. CLINICAL RELEVANCE: The use of BTX-B may improve the success rate of
      microvascular anastomoses by being protective against vasospastic stress and
      subsequent thrombosis.

PMID- 21855234
TI  - No influence of one right-sided prefrontal HF-rTMS session on alcohol craving in
      recently detoxified alcohol-dependent patients: results of a naturalistic study.
AB  - BACKGROUND: Prior research in substance dependence has suggested potential anti
      craving effects of repetitive transcranial magnetic stimulation (rTMS) when
      applied to the dorsolateral prefrontal cortex (DLPFC). However, no single sham
      controlled session studies applied to the right DLPFC have been carried-out in
      recently detoxified alcohol-dependent patients. Furthermore, no studies examined
      the effect of a single HF-rTMS session on craving in these patients' natural
      habitat. METHODS: To further investigate the effect of high-frequency (HF)-rTMS
      of the right DLPFC on alcohol craving, we performed a prospective, single-blind,
      sham-controlled study involving 36 hospitalized patients with alcohol dependence
      syndrome. After successful detoxification, patients were allocated receiving one
      active or one sham HF-rTMS session. The obsessive-compulsive drinking scale
      (OCDS) was administered to evaluate the extent of craving just before and after
      the HF-rTMS session (on Friday), on Saturday and Sunday during the weekend at
      home, and on Monday when the patient returned to the hospital. RESULTS: One
      single blind sham-controlled HF-rTMS session applied to the right DLPFC did not
      result in changes in craving (neither immediately after the stimulation session,
      nor in patients' natural environment during the weekend). CONCLUSIONS: One HF
      rTMS stimulation session applied to the right DLPFC had no significant effects on
      alcohol craving in alcohol dependent patients. One such session could have been
      too short to alter alcohol craving in a sample of alcohol dependent patients.

PMID- 21855235
TI  - Reward expectations lead to smoking uptake among depressed adolescents.
AB  - AIMS: While the comorbidity between adolescent depression and smoking has been
      well documented, less is known about why smoking is disproportionately higher
      among depressed adolescents. Emerging research suggests that reward-related
      mechanisms may be important to consider. This study sought to determine whether
      adolescents with higher depression symptoms have greater smoking reward
      expectations, which in turn, influence smoking progression. PARTICIPANTS: The
      sample was composed of 1393 adolescents participating in a longitudinal survey
      study of adolescent health behaviors. DESIGN AND MEASUREMENTS: In this
      prospective cohort study, variables were measured via self-report every six
      months from age 14 to age 17 resulting in six waves of data. Findings Parallel
      processes latent growth curve modeling indicated that higher depression symptoms
      across mid to late adolescence predicted a 17% increase in smoking reward
      expectations (beta=3.50, z=2.85, p=0.004), which in turn predicted a 23% increase
      in the odds of smoking progression (beta=0.206, z=3.29, p=0.001). The indirect
      effect was significant with delta method (beta(indirect)=0.72, z=3.09, p=0.002;
      95% CI=0.26, 1.18) and bootstrap (beta(indirect)=0.72, z=2.10, p=0.03; 95%
      CI=0.05, 1.39) standard errors. CONCLUSIONS: The study provides novel evidence
      that expectations of smoking reward facilitate smoking uptake among depressed
      adolescents. Smoking reward expectations may identify depressed adolescents at
      risk of smoking. Addressing alternative ways to meet the reward expectations
      rather than smoking may be an important component to consider in the preventing
      smoking and promoting smoking cessation among adolescents with elevated
      depression symptoms.

PMID- 21855237
TI  - Cultural adaptation of a parent completed social emotional screening instrument
      for young children: Ages And Stages Questionnaire-Social Emotional.
AB  - A major barrier to the identification and treatment of social and emotional
      problems in young children is the lack of psychometrically sound, low-cost,
      culturally and linguistically appropriate assessments, especially for the
      preschool population. While some screening instruments have been developed in the
      United States, very little or no interest in this area has materialized in Korea.
      One possible solution is an adaptation of an existing tool from the U.S. for use
      with Korean families. The present study investigated a Korean translation of the
      Ages and Stages Questionnaires: Social Emotional (ASQ:SE) by examining the
      appropriateness of the translation as well as its reliability and validity when
      studied with a large sample of Korean young children and their parents. Overall,
      findings were positive. Internal consistency for the Korean-translated ASQ:SE was
      strong, with an overall alpha of .68, ranging from .56 to .77. Test-retest
      reliability was .84 between ASQ:SE questionnaires completed by parents at
      successive time periods. Overall agreement of two questionnaire classifications
      (i.e., at risk, OK) completed by parents within one to four weeks was 94.
      Validity results, which were used to establish cutoff points and measure
      convergent validity, were also adequate. Further research on validity and
      reliability of the Korean ASQ:SE with a larger, more diverse sample is needed.

PMID- 21855236
TI  - Linking measures of adult nicotine dependence to a common latent continuum and a
      comparison with adolescent patterns.
AB  - BACKGROUND: An ongoing debate regarding the nature of nicotine dependence (ND) is
      whether the same instrument can be applied to measure ND among adults and
      adolescents. Using a hierarchical item response model (IRM), we examined evidence
      for a common continuum underlying ND symptoms among adults and adolescents.
      METHOD: The analyses are based on two waves of interviews with subsamples of
      parents and adolescents from a multi-ethnic longitudinal cohort of one thousand
      and thirty-nine 6-10th graders from the Chicago Public Schools (CPS). Adults and
      adolescents who reported smoking cigarettes the last 30 days prior to waves 3 and
      5 completed three common instruments measuring ND symptoms and one item measuring
      loss of autonomy. RESULTS: A stable continuum of ND, first identified among
      adolescents, was replicated among adults. However, some symptoms, such as
      tolerance and withdrawal, differed markedly across adults and adolescents. The
      majority of mFTQ items were observed within the highest levels of ND, the NDSS
      items within the lowest levels, and the DSM-IV items were arrayed in the middle
      and upper third of the continuum of dependence severity. Loss of autonomy was
      positioned at the lower end of the continuum. We propose a ten-symptom measure of
      ND for adolescents and adults. CONCLUSIONS: Despite marked differences in the
      relative severity of specific ND symptoms in each group, common instrumentation
      of ND can apply to adults and adolescents. The results increase confidence in the
      ability to describe phenotypic heterogeneity in ND across important developmental
      periods.

PMID- 21855238
TI  - Mixed squamous cell carcinoma and follicular carcinoma of the thyroid gland.
AB  - Primary squamous cell carcinoma of the thyroid gland (PSCCT) is rare and its
      aetiology is debated. A 67-year-old man presented with neck mass. Fine-needle
      aspiration (FNA) cytology and through-cut biopsy were suggestive of poorly
      differentiated or anaplastic carcinoma. The patient was offered tracheostomy and
      palliative cure for unresectable tumor of the thyroid; he refused and decided for
      other opinion. Lobe-isthmusectomy was performed with diagnostic and debulking
      intent. Final pathology report was of mixed squamous cell and follicular
      carcinoma of the thyroid. The tumor was a PSCCT. The patient underwent adjuvant
      chemoradiotherapy. After 2 years, an iliac crest metastasis of follicular
      carcinoma was diagnosed. The patient is disease free, after surgery and radio
      active-iodine treatment. The hypothesis of squamous cell carcinoma transformation
      from well differentiated thyroid cancer has to be considered in case of PSCCT.
      Primary squamous cell carcinoma of the thyroid gland (PSCCT) is rare [1-3];
      different theories on its aetiology do exist [4-6]. Mixed squamous cell and
      follicular carcinoma is even more rare than pure squamous cell of the thyroid
      gland and only few cases are reported in literature [7]. Preoperative diagnosis
      can be very challenging and the differential diagnosis with secondary squamous
      cell carcinoma of the thyroid (SSCCT) is manadatory in order to plan a correct
      management of the disease. The presence of PSCCT with distant metastasis of
      follicular carcinoma supports the histogenesis of squamous cell carcinomas
      arising from follicular epithelial cells.

PMID- 21855239
TI  - Impact of an intervention designed to improve the documentation of the
      reassessment of antibiotic therapies in an intensive care unit.
AB  - OBJECTIVES: The study objectives were: (i) to design an intervention to improve
      the written documentation of empiric antibiotic prescriptions' reassessment; (ii)
      and to assess the impact of this intervention on the quality of prescriptions.
      PATIENTS AND METHODS: A prospective before and after 7-month intervention study
      in a medical ICU in a French teaching hospital, using interrupted time-series
      analysis. The intervention was made to improve the documentation of four process
      measures in medical records: antibiotic plan, reviewing the diagnosis, adapting
      to positive microbiological results, and IV-per os switch. RESULTS: One hundred
      and fourteen antibiotic prescriptions were assessed, 62 before and 52 after the
      intervention. The reassessment of antibiotic prescriptions was more often
      documented in the ICU after the intervention (P=0.03 for sudden change). The
      prevalence of appropriate antibiotic prescriptions was not statistically
      different before and after the intervention, either for sudden change and/or
      linear trend. CONCLUSION: A better documentation of antibiotic prescriptions'
      reassessment was achieved in this ICU, but it did not improve the quality of
      antibiotic prescriptions.

PMID- 21855240
TI  - "MR conditional" respiratory ventilator system incident in a 3-T MRI environment.
AB  - The misunderstanding of the labeling for an "MR conditional" respiratory
      ventilator system resulted in the placement of this device, which had substantial
      ferromagnetic components, too close to a 3-T magnetic resonance (MR) system,
      causing a projectile incident. Magnetic resonance imaging health care
      professionals should be aware of the potentially dangerous consequences when such
      medical devices that have Food and Drug Administration-approved MR conditional
      labeling are brought into the MR system room. Recommendations to prevent future
      incidents are provided herein.

PMID- 21855241
TI  - Investigation of prostate cancer using diffusion-weighted intravoxel incoherent
      motion imaging.
AB  - PURPOSE: The objective of this work was to evaluate the diagnostic performance of
      the intravoxel incoherent motion (IVIM) model to differentiate between healthy
      and malignant prostate tissue. MATERIALS AND METHODS: Regions of interest were
      drawn in healthy and cancerous tissue of 13 patients with histologically proven
      prostate carcinoma and fitted to a monoexponential model [yielding the apparent
      diffusion coefficient (ADC)] and the IVIM signal equation (yielding the perfusion
      fraction f, the diffusion constant D and the pseudodiffusion coefficient of
      perfusion D*). Parameter maps were calculated for all parameters. RESULTS: The
      ADC, D and f were significantly (P<.005) lowered in cancerous tissue (1.01+/-0.22
      MUm(2)/ms, 0.84+/-0.19 MUm(2)/ms and 14.27+/-7.10%, respectively) compared to
      benign tissue (1.49+/-0.17 MUm(2)/ms, 1.21+/-0.22 MUm(2)/ms and 21.25+/-8.32%,
      respectively). Parameter maps of D and f allowed for a delineation of the tumor,
      but showed higher variations compared to the ADC map. CONCLUSION: Apparent
      diffusion coefficient maps provide better diagnostic performance than IVIM maps
      for tumor detection. However, the results suggest that the reduction of the ADC
      in prostate cancer stems not only from changes in cellularity but also from
      perfusion effects. IVIM imaging might hold promise for the diagnosis of other
      prostatic lesions.

PMID- 21855242
TI  - Automatic quantification of muscle volumes in magnetic resonance imaging scans of
      the lower extremities.
AB  - Muscle volume measurements are essential for an array of diseases ranging from
      peripheral arterial disease, muscular dystrophies, neurological conditions to
      sport injuries and aging. In the clinical setting, muscle volume is not routinely
      measured due to the lack of standardized ways for its repeatable quantification.
      In this paper, we present magnetic resonance muscle quantification (MRMQ), a
      method for the automatic quantification of thigh muscle volume in magnetic
      resonance imaging (MRI) scans. MRMQ integrates a thigh segmentation and
      nonuniform image gradient correction step, followed by feature extraction and
      classification. The classification step leverages prior probabilities,
      introducing prior knowledge to a maximum a posteriori classifier. MRMQ was
      validated on 344 slices taken from 60 MRI scans. Experiments for the fully
      automatic detection of muscle volume in MRI scans demonstrated an averaged
      accuracy, sensitivity and specificity for leave-one-out cross-validation of
      88.3%, 93.6% and 87.2%, respectively.

PMID- 21855243
TI  - In vivo measurement of normal rat intracellular pyruvate and lactate levels after
      injection of hyperpolarized [1-(13)C]alanine.
AB  - Hyperpolarized technology utilizing dynamic nuclear polarization has enabled
      rapid and high-sensitivity measurements of (13)C metabolism in vivo. The most
      commonly used in vivo agent for hyperpolarized (13)C metabolic imaging thus far
      has been [1-(13)C]pyruvate. In preclinical studies, not only is its uptake
      detected, but also its intracellular enzymatic conversion to metabolic products
      including [1-(13)C]lactate and [1-(13)C]alanine. However, the ratio of (13)C
      lactate/(13)C-pyruvate measured in this data does not accurately reflect cellular
      values since much of the [1-(13)C]pyruvate is extracellular depending on timing,
      vascular properties, and extracellular space and monocarboxylate transporter
      activity. In order to measure the relative levels of intracellular pyruvate and
      lactate, in this project we hyperpolarized [1-(13)C]alanine and monitored the in
      vivo conversion to [1-(13)C]pyruvate and then the subsequent conversion to [1
      (13)C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue
      measured with hyperpolarized [1-(13)C]alanine was 4.89+/-0.61 (mean+/-S.E.) as
      opposed to a ratio of 0.41+/-0.03 when hyperpolarized [1-(13)C]pyruvate was
      injected.

PMID- 21855244
TI  - Determination of major boswellic acids in plasma by high-pressure liquid
      chromatography/mass spectrometry.
AB  - Until now, dexamethasone is the medication of choice to reduce peritumoral edema
      associated with primary and secondary brain tumors. Because of the severe side
      effects accompanying such a treatment the interest in alternative agents that may
      be co-administered with glucocorticoids and help to reduce the required dose is
      constantly increasing. Boswellia serrata gum resin extracts (BSE), which have
      been designated an orphan drug status by the European Medicines Agency (EMA) in
      2002 for the treatment of peritumoral edema, may represent a promising
      supplemental herbal remedy. However, clinical studies on the effect of BSE on
      brain edema as well as analyzes of serum levels are very scarce. Based on that
      background a prospective, placebo controlled, and double blind clinical pilot
      trial was conducted on 14 patients applying for the first time a high dose of
      4200 mg BSE per day and 13 patients receiving placebo. For monitoring the serum
      levels of all major boswellic acids (BAs) a highly sensitive HPLC-MS method has
      been developed that allows the determination of KBA and AKBA from 5.0 ng/ml to
      3000 ng/ml and of alphaBA, betaBA, AalphaBA and AbetaBA from 0.5 ng/ml to 12,000
      ng/ml. It is the first validated method that covers such a wide concentration
      range, which makes it suitable to be used as standard method in clinical trials
      as it compensates for the great pharmacokinetic variability in the plasma levels
      of BAs observed in clinical practice. Average steady concentrations (ng/ml) in
      the range of 6.4-247.5 for KBA, 0-15.5 for AKBA, 36.7-4830.1 for alphaBA, 87.0
      11948.5 for betaBA, 73.4-2985.8 for AalphaBA and 131.4-6131.3 for AbetaBA were
      determined in the verum group. The here quantified steady state levels suggest
      betaBA to be a possible candidate for the anti-inflammatory and anti-edemateous
      effects of BSE. In general, the serum level analysis underlines the promising
      clinical results of BSE on cerebral edema.

PMID- 21855245
TI  - LC-MS/MS determination of betamethasone and its phosphate and acetate esters in
      human plasma after sample stabilization.
AB  - Two specific liquid chromatography-mass spectrometric (LC-MS/MS) assays were
      developed and validated for the determination of betamethasone (BET), and its
      acetate (BA) and phosphate (BP) esters. The plasma and the blood used for the
      development and validation of these two methods were previously stabilized.
      Liquid-liquid extraction techniques were used after the addition of prednisolone
      as internal standard (IS). Samples were chromatographed using C8 column, while
      mass detection was carried out by electrospray ionization in the positive mode
      (ESI+). The method was proved linear over a working range 0.50-50.00 ng/ml for
      BET (r(2)>0.99), while BA linear range was 1.0-20.0 ng/ml (r(2)>0.99).
      Sensitivity was determined as 0.50 ng/ml for BET and 1.00 ng/ml for BA.
      Betamethasone phosphate LC-MS/MS method involved solid phase extraction after the
      addition of prednisolone phosphate as (IS). Separation was carried out using C18
      column, while detection was by ESI+. The method showed good linearity over the
      working range 2.0-200.0 ng/ml (r(2)>099). Both methods were applied to determine
      BET, BA and BP in plasma samples obtained for pharmacokinetics studies in human.

PMID- 21855246
TI  - In vitro antibacterial activities of doripenem, imipenem, and meropenem against
      recent Streptococcus pneumoniae isolates.
AB  - We investigated the in vitro activities of carbapenems against 347 Streptococcus
      pneumoniae isolates from Korea. While doripenem and imipenem resistance was
      displayed by only 1.2% and 3.2%, respectively, 21.3% of the isolates were
      resistant to meropenem. One isolate displaying very high carbapenem MICs and
      susceptibility only to vancomycin was also identified.

PMID- 21855247
TI  - Establishing a serologic decision tree model of extrapulmonary tuberculosis by
      MALDI-TOF MS analysis.
AB  - Matrix-assisted laser desorption-ionization time of flight mass spectrometry
      (MALDI-TOF MS) combined with weak cationic exchange (WCX) magnetic beads was used
      to establish a decision tree model that distinguished extrapulmonary tuberculosis
      (EPTB) from non-EPTB individuals. Eight-one patients with EPTB and 112 non-EPTB
      individuals (72 disease controls and 40 healthy controls) were involved in this
      study. The model was set up by 5 of 19 differentially expressed peaks (P < 0.05),
      m/z 4100, 4310, 6093, 8605, and 14,019. This model can discriminate patients with
      EPTB from non-EPTB with a sensitivity of 97.7% and a specificity of 84.1%. The
      test set verified that this model had good sensitivity and specificity: 94.4% and
      83.6%, respectively. In conclusion, MALDI-TOF MS combined with WCX magnetic beads
      is a powerful technology for constructing a decision tree model and the model we
      built could serve as a potential diagnostic tool for EPTB.

PMID- 21855248
TI  - Combination therapy with daptomycin, linezolid, and rifampin as treatment option
      for MRSA meningitis and bacteremia.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is associated with
      a high mortality rate. Treatment is challenging in patients with allergy to
      vancomycin. Herein, we describe a case of MRSA bacteremia secondary to medical
      device infection with MRSA that was complicated by MRSA meningitis. This case
      provides evidence for a possible role of combination therapy of daptomycin,
      linezolid, and rifampin in cases of MRSA meningitis and bacteremia.

PMID- 21855249
TI  - Quantitative real-time polymerase chain reaction improves conventional
      microbiological diagnosis in an outbreak of brucellosis due to ingestion of
      unpasteurized goat cheese.
AB  - Rapid diagnosis of individuals involved in brucellosis outbreaks can sometimes be
      difficult with conventional microbiological techniques. We analyzed, for the
      first time, the diagnostic yield of a real-time polymerase chain reaction (PCR)
      assay in a family outbreak of brucellosis due to consumption of unpasteurized
      goat cheese. PCR correctly identified all symptomatic cases.

PMID- 21855250
TI  - Matrix-assisted laser desorption/ionization time-of-flight intact cell mass
      spectrometry to detect emerging pathogenic Candida species.
AB  - Matrix-assisted laser desorption/ionization time-of-flight intact cell mass
      spectrometry (MALDI-TOF-ICMS) was used to differentiate pathogenic Candida
      species, difficult to identify by traditional methods such as growth and
      biochemical reactions. Results showed that species complexes like C.
      parapsilosis, C. orthopsilosis, and C. metapsilsosis, and very closely related
      species like C. glabrata and C. bracarensis, and C. albicans and C. dubliniensis
      could be clearly separated. MALDI-TOF-ICMS stands out as a promising tool for the
      rapid detection of emerging pathogens.

PMID- 21855251
TI  - Diagnosis of pneumonia in the ED has poor accuracy despite diagnostic
      uncertainty.
AB  - BACKGROUND: In 2007, the Centers for Medicare and Medicaid Services created a
      measure known as "diagnostic uncertainty" in emergency department (ED) pneumonia
      admissions. This documentation excludes the antibiotic timing measure, as
      pressure to quickly diagnose pneumonia may serve to reduce overall accuracy.
      STUDY OBJECTIVES: The objective of the study was to determine the correlation
      between ED and final discharge diagnosis of pneumonia and measure the effect of
      invoking the diagnostic uncertainty documentation on accuracy. METHODS: We
      retrospectively reviewed all ED pneumonia admissions among adults from July to
      October 2008. We analyzed the effect of invoking the diagnostic uncertainty
      documentation in the ED by comparing against final outcomes. We then performed a
      multivariate analysis to adjust for the potential effects of sex, age, Emergency
      Severity Index (ESI) score, weekend arrival, and level of ED-attending physician
      staffing. RESULTS: Of 401 patients who were admitted with pneumonia, 297 (74%)
      had a discharge diagnosis of pneumonia, with 72 (18%) of those diagnoses being
      the primary outcome. Diagnostic uncertainty documentation was used in 11%
      (45/401). This documentation did not significantly alter the odds of a primary
      pneumonia discharge diagnosis (odds ratio, 0.68; 95% confidence interval, 0.28
      1.7) but did reduce the odds of pneumonia being diagnosed (odds ratio, 0.43; 95%
      confidence interval, 0.23-0.81). Sex, age, day of week, and (ESI) score remained
      nonsignificant predictors. CONCLUSIONS: Correlation between ED and discharge
      diagnosis of pneumonia was limited. Use of diagnostic uncertainty documentation
      decreased the likelihood of a hospital discharge diagnosis of pneumonia. Further
      analysis of the effects of artificially imposed time constraints on ED diagnoses
      appears warranted.

PMID- 21855252
TI  - Morbidly obese patients receive delayed ED care: body mass index greater than 40
      kg/m2 have longer disposition times.
AB  - OBJECTIVES: Our study compares treatment times of morbidly obese patients (body
      mass index [BMI]>40 kg/m2) with patients having BMI less than 35 kg/m2. METHODS:
      We used an institutional review board-approved, retrospective, sequential,
      cohort, data analysis of emergency department (ED) medical records from our
      county teaching hospital (January 2010). Our data set of 102 morbidly obese
      patients (World Health Organization class 3 [BMI>40 kg/m2]) was compared with
      that of 195 normal or mildly obese patients (World Health Organization class 0 or
      1 [BMI<35 kg/m2]). Inclusion was limited to patients of Emergency Severity Index
      level 2 and 3 who presented for triage. The primary outcome variable was total
      length of stay for patients discharged home from the ED. RESULTS: Morbidly obese
      patients take significantly longer to disposition than normal or mildly obese
      patients (difference, 101 minutes [95% CI, 55-146]; P<.0001). The mean length of
      stay for patients with BMI less than 35 kg/m2 was 287 minutes in contrast to 388
      minutes for patients with BMI greater than 40 kg/m2. Computed tomography use was
      significantly less likely in the BMI class 0 and 1 groups compared with the BMI
      class 3 group (0.41 [79/195] vs 0.56 [57/102]; difference, 0.15 [95% CI, 0.03
      0.27]; P=.012). CONCLUSIONS: In our institution, morbidly obese patients take
      significantly longer to disposition home than patients of more normal weight.

PMID- 21855253
TI  - The fifth chamber of the heart: huge left atrial aneurysm.
AB  - Cardiomegaly is a common but nonspecific finding in the emergency department. The
      etiology may be explained by left ventricular dilation, biventricular dilation,
      right ventricular dilation, or pericardial abnormalities, or it may be found to
      be spurious on the echocardiogram. Rarely, isolated abnormalities of the atrium,
      particularly the left atrium, may cause abnormalities on the chest radiograph but
      will not cause true cardiomegaly. We reported a 37-year-old woman who presented
      with persistent palpitation of a 6-hour duration. An electrocardiogram revealed
      atrial fibrillation with rapid ventricular response. A chest radiograph showed
      cardiomegaly with unusual prominence of the left heart border. A subsequent
      transthoracic echocardiography demonstrated an echo-free chamber adjacent to the
      left lateral wall of the left ventricle. The diagnosis of a rare huge left atrial
      aneurysm was finally established by multidetector-row computed tomography, which
      had been seldom used as a diagnostic tool in the past. Patients with this cardiac
      anomaly usually are asymptomatic until the second or third decade of life, when
      the aneurysms can reach remarkable sizes and are often complicated with atrial
      tachyarrhythmia or thromboembolic events. Early surgical intervention is advised
      even in asymptomatic patients to prevent the occurrence of myocardial
      dysfunction, atrial fibrillation, and systemic embolism.

PMID- 21855254
TI  - Bruns-Cushing nystagmus due to hypertensive unilateral paramedian pontine base
      infarction.
AB  - Bruns-Cushing nystagmus is unusually rare and is known to be related with
      cerebellopontine angle tumor. A 32-year-old male patient came to our emergency
      department 3 times because of dizziness, right upper limb ataxia, hypertension,
      and Bruns-Cushing nystagmus. Magnetic resonance imaging demonstrated left
      paramedian pontine infarction. In conclusion, Bruns-Cushing nystagmus not only
      indicates a cerebellopontine angle tumor but may also be associated with pontine
      infarction.

PMID- 21855255
TI  - Predictive accuracy of ST depression during rapid atrial fibrillation on the
      presence of obstructive coronary artery disease.
AB  - BACKGROUND: Rapid atrial fibrillation (AF) is commonly associated with ST-segment
      depressions. ST-segment depression during a chest pain episode or exercise stress
      testing in sinus rhythm is predictive of obstructive coronary artery disease
      (CAD), but it is unclear if the presence or magnitude of ST-segment depression
      during rapid AF has similar predictive accuracy. METHODS: One hundred twenty
      seven patients with rapid AF (heart rate >=120 beats per minute) who had cardiac
      catheterization performed during the same hospital admission were retrospectively
      reviewed. Variables to compute thrombolysis in myocardial infarction (TIMI) risk
      score, demographic profiles, ST-segment deviation, cardiac catheterization
      results, and cardiac interventions were collected. RESULTS: Thirty-five patients
      had ST-segment depression of 1 mm or more, and 92 had no or less than 1 mm ST
      depression. Thirty-one patients were found to have obstructive CAD. In the group
      with ST-segment depression, 11 (31%) patients had obstructive CAD and 24 (69%)
      did not. In the group with less than 1 mm ST-segment depression, 20 (22%) had
      obstructive CAD and 72 (78%) did not (P = .25). Sensitivity, specificity, and
      positive and negative predictive values for presence of obstructive CAD were 35%,
      75%, 31%, and 78%, respectively. The presence of ST-segment depression of 1 mm or
      more was not associated with presence of obstructive CAD before or after
      adjustment of TIMI variables. The relationship between increasing grades of ST
      segment depression and obstructive CAD showed a trend toward significance (P =
      .09), which did not persist after adjusting for TIMI risk variables (P = .36).
      CONCLUSION: ST-segment depression during rapid AF is not predictive for the
      presence of obstructive CAD.

PMID- 21855256
TI  - ED point-of-care ultrasound in the diagnosis of ankle fractures in children.
AB  - In pediatric ankle injury, radiography is the current standard used to
      differentiate fracture from ligamentous injury; however, the associated cost,
      increased time, and radiation exposure pose a significant downside to this
      imaging modality. Point-of-care ultrasound may be an attractive alternative in
      this setting, as illustrated by this patient case. A 14-year-old boy presented to
      the emergency department with a left ankle inversion injury sustained while
      playing soccer. An emergency physician performed ultrasound examination that
      revealed findings consistent with a nondisplaced Salter-Harris I fracture of the
      distal fibula. The results of a formal radiograph confirmed this diagnosis. This
      case report presents the successful use of point-of-care ultrasound for detection
      of a Salter-Harris I ankle fracture, describes a stepwise approach for this new
      diagnostic technique in detail, and discusses its value in the setting of
      pediatric ankle injury.

PMID- 21855257
TI  - Nail bed injury detected by ultrasonography.
AB  - A 46-year-old man presented to the emergency department after being injured with
      a press machine from his left hand 30 minutes before admission. Subungual
      hematoma was diagnosed in his index finger, although the nail plate was intact.
      Emergency physicians could identify nail bed injury with bedside ultrasonography
      examination. This noninvasive, inexpensive, and repeatable diagnostic modality
      could preserve patients from a complex, invasive nail removal procedure.

PMID- 21855258
TI  - Mondor disease: a case report in ED.
AB  - Mondor disease is a form of superficial thrombophlebitis affecting the
      subcutaneous veins, specifically of the anterolateral thoracoabdominal wall.
      Clinical presentation is commonly a subcutaneous, tender, painful cordlike
      induration, usually founded in the breast or axilla. It affects typically middle
      aged women. A 36-year-old patient was admitted to the emergency department to a
      chest discomfort and to discovery of a palpable, nonerythematous, and painful
      cordlike structure running from the inferior pole of her left breast to the left
      iliac pit. She had no history of trauma, injury, or intensive physical activity.
      Ultrasonography confirmed thrombosis of the thoracoepigastric vein. A
      thrombophilic workup performed 2 years ago was normal. The patient was treated by
      enoxaparin 1 mg/kg per day for 30 days. Evolution was favorable. The etiology of
      Mondor disease remains unclear. Predisposing factors are mainly trauma, excessive
      physical activity, surgery, infections. Ultrasonography is used to confirm the
      diagnosis. Coagulation tests should be performed to exclude hypercoagulability
      condition. In the past, symptomatic approach with anti-inflammatory drugs was
      proposed. Recent guidelines suggest prophylactic or intermediate doses of low
      molecular-weight heparin for at least 4 weeks. Although uncommon, Mondor disease
      has to be recognized to avoid useless diagnosis testing and to deliver a specific
      treatment.

PMID- 21855259
TI  - Asystole after the first dose of ceftriaxone.
AB  - The incidence of ceftriaxone-related hypersensitivity skin reactions is between
      1% and 3%, whereas anaphylaxis is rare. To the best of our knowledge, the
      following case is the first report of asystole after the administration of single
      dose ceftriaxone. A 55-year-old man was admitted to our emergency department
      because of high fever, abdominal pain, dysuria, and weakness. To determine the
      cause of his fever, blood and urine cultures were obtained. Then, an infusion of
      1 g ceftriaxone was started slowly. One minute later, cardiac arrest occurred.
      The rhythm was asystole. Cardiopulmonary resuscitation and tracheal intubation
      were performed immediately, and the ceftriaxone infusion was discontinued. Within
      20 minutes, circulation was restored. The time of onset was suggestive of
      ceftriaxone-induced anaphylaxis. The patient was discharged in good clinical
      condition on the 10th day of admission. Emergency physicians should be mindful of
      the possibility of anaphylaxis and asystole that could occur with the first dose
      of ceftriaxone and should also make sure to offer receiving detailed informed
      patient consent, too.

PMID- 21855260
TI  - Answering the myth: use of emergency services on Friday the 13th.
AB  - OBJECTIVE: The aim of the study was to evaluate the risk of Friday the 13th on
      hospital admission rates and emergency department (ED) visits. METHODS: This was
      a retrospective chart review of all ED visits on Friday the 13th from November
      13, 2002, to December 13, 2009, from 6 hospital-based EDs. Thirteen unlikely
      conditions were evaluated as well as total ED volumes. As a control, the Friday
      before and after and the month before and after were used. chi(2) Analysis and
      Wilcoxon rank sum tests were used for each variable, as appropriate. RESULTS: A
      total of 49 094 patient encounters were evaluated. Average ED visits for Friday
      the 13th were not increased compared with the Friday before and after and the
      month before. However, compared with the month after, there were fewer ED visits
      on Friday the 13th (150.1 vs 134.7, P = .011). Of the 13 categories evaluated,
      only penetrating trauma was noted to have an increase risk associated with Friday
      the 13th (odds ratio, 1.65; 95% confidence interval, 1.04-2.61). No other
      category was noted to have an increase risk on Friday the 13th compared with the
      control dates. CONCLUSIONS: Although the fear of Friday the 13th may exist, there
      is no worry that an increase in volume occurs on Friday the 13th compared with
      the other days studies. Of 13 different conditions evaluated, only penetrating
      traumas were seen more often on Friday the 13th. For those providers who work in
      the ED, working on Friday the 13th should not be any different than any other
      day.

PMID- 21855261
TI  - How reliable are patient-completed medication reconciliation forms compared with
      pharmacy lists?
AB  - OBJECTIVES: Medication reconciliation is a Joint Commission for the Accreditation
      of Healthcare Organizations requirement to reduce medication errors. This study
      evaluated the reliability of patient-completed medication reconciliation forms
      (MRs) compared with pharmacy-generated lists and determined if there was a
      difference in concordance when patients completed the forms from memory compared
      with when they brought a separate list or pill bottles. METHODS: We prospectively
      enrolled patients with completed MRs. Research assistants contacted the patient's
      pharmacy to determine medications filled in the prior 3 months, which was
      compared with the MR. Discrepancies and the method by which the patient completed
      the MR (memory, list, or pill bottles) were recorded. RESULTS: Three hundred
      fifteen patients were enrolled. Thirty-three percent made errors of omission
      (reported by pharmacy, but not on MR), 12.7% made errors of addition (reported on
      MR, but not by pharmacy), 18.1% made both types of errors, and 36.3% made no
      errors. Patients with errors were on 5.6 medications compared with 3.6
      medications for those without errors (P < .0001). Those completing the MR from a
      list made 2.3 errors compared with 1.2 for those completing from memory and 1.8
      for those completing from their pill bottles (P < .001). Of 390 medications
      omitted from patient lists, 16% were cardiac medications, 13% were
      neuropsychiatric agents, and 9.5% were narcotics. CONCLUSIONS: Thirty-six percent
      of patients were able to provide a medication list that matched their pharmacy
      prescribed drugs. More errors were noted from patients taking more medications
      and from those completing their MR from a separate list.

PMID- 21855262
TI  - Drug-induced visual impairment may be a manifestation of acute angle closure
      glaucoma.

PMID- 21855263
TI  - Risk factors and outcome of Pseudomonas aeruginosa bacteremia among adults
      visiting the ED.
AB  - OBJECTIVES: The aim of this study was to determine the clinical characteristics
      of, antibiotic therapy for, and clinical outcome of Pseudomonas aeruginosa
      infection among bacteremic adults who visit the emergency department (ED).
      METHODS: Bacteremic adults who visited the ED were identified retrospectively
      from January 2007 to December 2007. Demographic characteristics, underlying
      illnesses, severity, bacteremic pathogens, antimicrobial agents, and outcome were
      determined from chart records. RESULTS: The records of 340 eligible bacteremic
      adults were analyzed; their mean age was 66.2 years, and major comorbidities
      included hypertension (175 patients, or 51.5%), diabetes mellitus (124, or
      36.5%), and malignancy (87, or 25.6%). Among the 379 bacteremic isolates,
      Escherichia coli (139 isolates, or 6.6%) and Klebsiella pneumoniae (63, or 16.6%)
      were the major pathogens, whereas P aeruginosa (15, or 4.0%) was the third
      leading gram-negative isolate. Of note, both 30-day mortality (33.3% vs 8.9%, P =
      .01) and the proportion of empirically inappropriate antibiotics (86.7% vs 31.4%,
      P < .001) were higher in bacteremia caused by P aeruginosa than in bacteremia not
      caused by P aeruginosa in univariate analysis. Moreover, multivariate analysis
      identified 3 independent factors related to P aeruginosa bacteremia: surgery
      during the 4 weeks before ED arrival (adjusted odds ratio [AOR], 12.7; 95%
      confidence interval [CI], 1.68-95.7; P = .01), malignancy (AOR, 4.57; 95% CI,
      1.27-16.3; P = .02), and community onset (AOR, 0.14; 95% CI, 0.04-0.47; P =
      .002). CONCLUSIONS: For bacteremic adults who visited the ED, P aeruginosa was
      associated with a high mortality rate and a high proportion of empirically
      inappropriate antibiotic therapy. Identification of clinical predictors of P
      aeruginosa bacteremia would improve the quality of care and the use of
      appropriate antibiotics in the ED.

PMID- 21855264
TI  - Acute appendicitis: emergency medicine physician and surgeon clinical judgment vs
      abdominal computed tomography scan.

PMID- 21855265
TI  - Recipients of hyperbaric oxygen treatment for carbon monoxide poisoning and
      exposure circumstances.
AB  - BACKGROUND: Unintentional carbon monoxide poisoning is preventable. Severe cases
      are often referred for hyperbaric oxygen treatment. To guide prevention efforts
      and treatment practices, this study provides some of the most detailed current
      information about patients with carbon monoxide poisoning who have been treated
      at hyperbaric facilities across the United States and the circumstances
      surrounding their exposures. This study can help improve efforts to prevent
      carbon monoxide poisoning and enhance treatment practices. METHODS: From August
      2008 to January 2010, nonidentifiable, patient-level data were reported by 87
      hyperbaric facilities in 39 states via an online reporting system. This reporting
      system was developed collaboratively by the Undersea and Hyperbaric Medical
      Society and the Centers for Disease Control and Prevention. RESULTS: Among the
      864 patients reported to receive hyperbaric oxygen treatment for unintentional,
      non-fire-related, carbon monoxide poisoning, most of the patients were white men
      aged between 18 and 44 years. Only 10% of patients reported the presence of a
      carbon monoxide alarm at their exposure location, and 75% reported being part of
      a group exposure. Nineteen patients (2%) reported a prior carbon monoxide
      exposure. About half (55%) of the patients treated were discharged after
      treatment; 41% were hospitalized. CONCLUSIONS: The findings in this report expand
      the knowledge about patients with carbon monoxide poisoning. These results
      suggest that prevention efforts, such as educating the public about using carbon
      monoxide alarms and targeting the most at-risk populations, may help reduce the
      number of exposures, the number of persons with chronic cognitive sequelae, and
      the resulting burden on the health care system.

PMID- 21855266
TI  - Patient reported interpersonal processes of care and perceived social position:
      the Diabetes Study of Northern California (DISTANCE).
AB  - OBJECTIVE: A patient's sense of his/her standing in the social hierarchy may
      impact interpersonal processes of care (IPC) within the patient-provider
      encounter. We investigated the association of perceived social position with
      patient-reported IPC. METHODS: We used survey data from the Diabetes Study of
      Northern California (DISTANCE), studying 11,105 insured patients with diabetes
      cared for in an integrated healthcare delivery system. Perceived social position
      was based on the MacArthur subjective social status ladder. Patient-reported IPC
      was based on a combined scale adapted from the Consumer Assessment of Health
      Plans Study provider communication subscale and the Trust in Physicians scale.
      RESULTS: Lower perceived social position was associated with poorer reported IPC
      (p<0.001). The relationship remained statistically significant after controlling
      for age, sex, race/ethnicity, depressive symptoms, physical functioning, income
      and education. CONCLUSION: Beyond objective measures of SES, patients' sense of
      where they fall in the social hierarchy may represent a pathway between social
      position and patient satisfaction with the quality of patient-provider
      communication in chronic disease. PRACTICE IMPLICATIONS: Interventions to address
      disparities in communication in primary care should incorporate notions of
      patients' social position.

PMID- 21855267
TI  - Magnetic resonance for assessment of axillary lymph node status in early breast
      cancer: a systematic review and meta-analysis.
AB  - INTRODUCTION: Current methods of identifying axillary node metastases in breast
      cancer patients are highly accurate, but are associated with several adverse
      events. This review evaluates the diagnostic accuracy of magnetic resonance
      imaging (MRI) techniques for identification of axillary metastases in early stage
      newly diagnosed breast cancer patients. METHODS: Comprehensive searches were
      conducted in April 2009. Study quality was assessed. Sensitivity and specificity
      were meta-analysed using a bivariate random effects approach, utilising
      pathological diagnosis via node biopsy as the comparative gold standard. RESULTS:
      Based on the highest sensitivity and specificity reported in each of the nine
      studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78
      96%; range 65-100%) and mean specificity 90% (95% CI: 75-96%; range 54-100%).
      Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)
      enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61-100%) and mean
      specificity 96% (95% CI: 72-100%). Across three studies of gadolinium-enhanced
      MRI (n = 187), mean sensitivity was 88% (95% CI: 78-94%) and mean specificity 73%
      (95% CI: 63-81%). In the single study of in-vivo proton MR spectroscopy (n = 27),
      sensitivity was 65% (95% CI: 38-86%) and specificity 100% (95% CI: 69-100%).
      CONCLUSIONS: USPIO-enhanced MRI showed a trend towards higher sensitivity and
      specificity and may make a useful addition to the current diagnostic pathway.
      Additional larger studies with standardised methods and standardised criteria for
      classifying a node as positive are needed. Current estimates of sensitivity and
      specificity do not support replacement of SLNB with any current MRI technology in
      this patient group.

PMID- 21855268
TI  - Cost-effectiveness analysis of the most common orthopaedic surgery procedures:
      knee arthroscopy and knee anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to determine the cost-effectiveness of
      knee arthroscopy and anterior cruciate ligament (ACL) reconstruction. METHODS:
      Retrospective analysis of prospectively collected data from a single-surgeon,
      institutional review board-approved outcomes registry included 2 cohorts:
      surgically treated knee arthroscopy and ACL reconstruction patients. Our outcome
      measure is cost-effectiveness (cost of a quality-adjusted life-year [QALY]). The
      QALY is calculated by multiplying difference in health-related quality of life,
      before and after treatment, by life expectancy. Health-related quality of life is
      measured by use of the Quality of Well-Being scale, which has been validated for
      cost-effectiveness analysis. Costs are facility charges per the facility cost-to
      charges ratio plus surgeon fee. Sensitivity analyses are performed to determine
      the effect of variations in costs or outcomes. RESULTS: There were 93 knee
      arthroscopy and 35 ACL reconstruction patients included at a mean follow-up of
      2.1 years. Cost per QALY was $5,783 for arthroscopy and $10,326 for ACL
      reconstruction (2009 US dollars). Sensitivity analysis shows that our results are
      robust (relatively insensitive) to variations in costs or outcomes. CONCLUSIONS:
      Knee arthroscopy and knee ACL reconstruction are very cost-effective.

PMID- 21855269
TI  - [Withdrawal marketing of thiopental (Pentothal) by the Hospira - France company:
      a bad news that will announce probably others].

PMID- 21855270
TI  - Early biological fixation of porous implant coated with paste-retaining
      recombinant bone morphogenetic protein 2.
AB  - The aim of this study was to evaluate the period required for stable initial bone
      implant fixation with recombinant human bone morphogenetic protein 2 (rhBMP-2) in
      the bone marrow of a rabbit model. The porous implants being coated with beta
      tricalcium phosphate/polylactide-polyethylene glycol paste with 15, 30, or 60 MUg
      of rhBMP-2 (n = 10) were implanted into animals in 3 experimental groups. In 2
      control groups, the test implants were coated without rhBMP or no paste. In all
      groups, the implant was inserted for 3 and 6 weeks. At 3 weeks after
      implantation, the BMP-treated implants in the 2 lower dose groups had
      significantly more bone ingrowth to the implant surface than did the control
      groups, and the greatest effect occurred in the 30-MUg rhBMP-2 group animals.

PMID- 21855271
TI  - Is hydroxyapatite coating necessary to improve survivorship of porous-coated
      titanium femoral stem?
AB  - We compared the clinical and radiologic results in 55 patients (110 hips)
      associated with proximally porous-coated titanium stems that were identical in
      geometry but differed with regard to proximal surface treatment (with or without
      hydroxyapatite coating). The mean age at the time of the operation was 46.3 years
      (27-63 years), and mean length of follow-up was 15.6 years (15-16 years). The
      mean Harris hip score in both groups improved from 39 points and 41 points,
      respectively, to 93 and 91 points, respectively, at the last follow-up. After 16
      years, the cumulative survival for the stem was 100% in both groups and for the
      cup was 89% in both groups. After long-term follow-up, hydroxyapatite coating on
      the porous surfaces did not improve or diminish the results of total hip
      arthroplasty.

PMID- 21855272
TI  - The use of interlocking prostheses for both temporary and definitive management
      of infected periprosthetic femoral fractures.
AB  - Infected periprosthetic fractures around total hip arthroplasties are an
      extremely challenging problem. We describe our experience of managing infected
      periprosthetic femoral fractures using interlocking long-stem femoral prostheses
      either as temporary functional spacers or as definitive implants. The Cannulock
      (Orthodesign, Christchurch, United Kingdom) uncoated stem was used in 12 cases,
      and the Kent hip prosthesis (Biomet Merck, Bridgend, United Kingdom), in 5 cases.
      Satisfactory outcome was noted in all cases, and in 11 cases, revision to a
      definitive stem has been undertaken after successful control of infection and
      fracture union. The use of interlocking stems offers a relatively appealing
      solution for a complex problem and avoids the complications that would be
      associated with resection of the entire femur or the use of large quantities of
      bone cement.

PMID- 21855273
TI  - Patterns of osseointegration and remodeling in femoral revision with bone loss
      using modular, tapered, fluted, titanium stems.
AB  - Radiographic signs of osseointegration with the use of fluted, tapered, modular,
      titanium stems in revision hip arthroplasty with bone loss have not been
      previously categorized. Serial radiographs of 64 consecutive hips with mean
      follow-up of 6.2 years were retrospectively reviewed. Bone loss was classified as
      per Paprosky classification, osseointegration was assessed according to a
      modified system of Engh et al, and Harris Hip Score was used to document pain and
      function. Seventy-four percent of the hips had type 3 or 4 bone loss. All stems
      were radiographically osseointegrated. Early minor subsidence was seen in 6.2% of
      the hips; definite bony regeneration, 73% of the hips; and stress shielding, 26%
      of the hips. These osseointegration patterns were different from those described
      for extensively porous-coated cobalt-chromium stems and had a bearing on the
      evaluation of fixation of these stems.

PMID- 21855274
TI  - Early clinical results of a high-flexion, posterior-stabilized, mobile-bearing
      total knee arthroplasty: a US investigational device exemption trial.
AB  - Between May 2001 and June 2004, 388 total knee arthroplasty cases were enrolled
      in a prospective, randomized, multicenter investigational device exemption trial.
      Patients received either the investigational high-flexion mobile-bearing knee or
      a fixed-bearing control. At 2 to 4 years of follow-up, results in 293 patients
      with degenerative joint disease were compared using Knee Society Assessment and
      Function scores, radiographic results, complications analysis, and survival
      estimates. The mobile-bearing and fixed-bearing groups demonstrated similar,
      significant improvement over preoperative assessments in Knee Scores, maximum
      flexion, and range of motion. One mobile-bearing arthroplasty required revision.
      Radiographic results were unremarkable, and implant-related complications were
      rare in both groups. At this early follow-up, the investigational high-flexion
      mobile-bearing knee and its fixed-bearing counterpart demonstrated comparable,
      effective performance.

PMID- 21855275
TI  - 15-year experience with soft tissue expansion in total knee arthroplasty.
AB  - Preoperative identification of a knee at risk for wound healing after total knee
      arthroplasty (TKA) allows the surgeon to apply a soft tissue expansion technique
      to expand the available tissue for closure and healing after TKA. A consecutive
      series of 64 soft tissue expansions were performed for 59 cases of conflicting
      incisions and 5 cases of severe angular deformity, with a mean of 3.5 previous
      surgeries. An average 2.1 expanders were used for a total volume of 359 mL.
      Expansion took a mean of 70 days during which 14 minor and 7 major complications
      occurred. There were 8 post-TKA complications, 5 of which required a return to
      the operating room. Soft tissue expansion is a safe, prophylactic technique that
      provides adequate coverage in this complex subset of patients.

PMID- 21855276
TI  - Early results of total hip arthroplasty in patients with developmental dysplasia
      of the hip compared with patients with osteoarthritis.
AB  - We have investigated the results of primary total hip arthroplasty (THA)
      performed in patients with developmental dysplasia of the hip (DDH). Through the
      New Zealand Joint Registry, we identified all patients with DDH undergoing
      primary THA (n = 1205) and all patients with primary osteoarthritis (OA)
      undergoing primary THA (n = 40 589) between January 1, 1999, and December 31,
      2008. Postoperative outcomes, baseline information, and operative characteristics
      were analyzed and compared between the DDH and the OA groups. There was no
      significant difference in Oxford Hip Score or revision rate between the 2 groups.
      Our results support THA as a successful surgical option in the management of
      degenerative arthritis in DDH, with comparable functional outcomes and revision
      rates to THA performed for primary OA.

PMID- 21855277
TI  - Fracture propagation propensity of ceramic liners during impingement-subluxation:
      a finite element exploration.
AB  - Although improvements in materials engineering have greatly reduced fracture
      rates in ceramic femoral heads, concerns still exist for liners. Ceramics are
      vulnerable to fracture due to impact and from stress concentrations (point and
      line loading) such as those associated with impingement-subluxation. Thus,
      ceramic cup fracture propensity is presumably very sensitive to surgical cup
      positioning. A novel fracture mechanics finite element formulation was developed
      to identify cup orientations most susceptible to liner fracture propagation for
      several impingement-prone patient maneuvers. Other factors being equal, increased
      cup inclination and increased anteversion were found to elevate fracture risk.
      Squatting, stooping, and leaning shoe-tie maneuvers were associated with the
      highest fracture risk. These results suggest that fracture risk can be reduced by
      surgeons' decreasing cup abduction and by patients' avoiding of specific
      activities.

PMID- 21855278
TI  - Treatment of periprosthetic fractures around hip resurfacings with
      cephalomedullary nails.
AB  - We describe 2 cases of proximal femoral fractures, 1 intertrochanteric and 1
      subtrochanteric, distal to hip resurfacing implants that were managed
      successfully via internal fixation with trochanteric start point cephalomedullary
      nails. Both patients had pain-free, well-functioning implants with
      radiographically healed fractures at their 1-year follow-up. This novel approach
      offers several advantages over previously described techniques for these rare and
      difficult-to-treat fractures.

PMID- 21855279
TI  - Variability in the approach to total hip arthroplasty in patients with displaced
      femoral neck fractures.
AB  - The aim of this study was to determine the degree of variability in implants,
      approaches, and associated complication rates in randomized controlled trials
      (RCTs) evaluating primary total hip arthroplasty (THA) as an intervention for
      displaced femoral neck fractures. We searched 2 medical databases for RCTs
      involving THA for femoral neck fractures published between June 2000 and June
      2010. All analyses were descriptive. Nine RCTs met our inclusion criteria. We
      identified variability in both the surgical approach and choice of prosthesis.
      Trials generally standardized to head sizes of 28 mm or greater and cemented
      prostheses. Surgical experience varied across studies. Dislocation rates varied
      from 0% to 22%. There is considerable variability in RCTs evaluating THA for
      femoral neck fractures. Standardization toward optimal outcomes for femoral neck
      fractures is needed.

PMID- 21855280
TI  - Variation of left ventricular outflow tract velocity and global end-diastolic
      volume index reliably predict fluid responsiveness in cardiac surgery patients.
AB  - PURPOSE: The ability of the global end-diastolic volume index (GEDVI) and
      respiratory variations in left ventricular outflow tract velocity
      (DeltaVTI(LVOT)) for prediction of fluid responsiveness is still under debate.
      The aim of the present study was to challenge the predictive power of GEDVI and
      DeltaVTI(LVOT) compared with pulse pressure variation (PPV) and stroke volume
      variation (SVV) in a large patient population. MATERIAL AND METHODS: Ninety-two
      patients were studied before coronary artery surgery. Each patient was monitored
      with central venous pressure (CVP), the PiCCO system (Pulsion Medical Systems,
      Munich, Germany), and transesophageal echocardiography. Responders were defined
      as those who increased their stroke volume index by greater than 15%
      (DeltaSVI(TPTD) >15%) during passive leg raising. RESULTS: Central venous
      pressure showed no significant correlation with DeltaSVI(TPTD) (r = -0.06, P =
      .58), in contrast to PPV (r = 0.71, P < .0001), SVV (r = 0.61, P < .0001), GEDVI
      (r = -0.54, P < .0001), and DeltaVTI(LVOT) (r = 0.54, P < .0001). The best area
      under the receiver operating characteristic curve (AUC) predicting DeltaSVI(TPTD)
      greater than 15% was found for PPV (AUC, 0.82; P < .0001) and SVV (AUC, 0.77; P <
      .0001), followed by DeltaVTI(LVOT) (AUC, 0.74; P < .0001) and GEDVI (AUC, 0.71; P
      = .0006), whereas CVP was not able to predict fluid responsiveness (AUC, 0.58; P
      = .18). CONCLUSIONS: In contrast to CVP, GEDVI and DeltaVTI(LVOT) reliably
      predicted fluid responsiveness under closed-chest conditions. Pulse pressure
      variation and SVV showed the highest accuracy.

PMID- 21855281
TI  - Critically ill patients with cancer and sepsis: clinical course and prognostic
      factors.
AB  - PURPOSE: The purposes of this study were to evaluate the clinical course and to
      identify independent predictors of mortality in patients with cancer with sepsis.
      MATERIALS AND METHODS: This is a secondary analysis of a prospective cohort study
      conducted at an oncological medical-surgical intensive care unit. Logistic
      regression was used to identify predictors of hospital mortality. RESULTS: A
      total of 563 patients (77% solid tumor, 23% hematologic malignancies) were
      included over a 55-month period. The most frequent sites of infection were the
      lung, abdomen, and urinary tract; 91% patients had severe sepsis/septic shock.
      Gram-negative bacteria were responsible for more than half of the episodes of
      infection; 38% of patients had polymicrobial infections. Intensive care unit,
      hospital, and 6-month mortality rates were 51%, 65%, and 72%, respectively. In
      multivariate analyses, sepsis in the context of medical complications; active
      disease; compromised performance status; presence of 3 to 4 systemic inflammatory
      response syndrome criteria; and the presence of respiratory, renal, and
      cardiovascular failures were associated with increased mortality. Adjusting for
      other covariates, patients with non-urinary tract infections, mostly represented
      by patients with pneumonia and abdominal infections, had worse outcomes.
      CONCLUSIONS: Sepsis remains a frequent complication in patients with cancer and
      associated with high mortality. Our results can be of help to assist intensivists
      in clinical decisions and to improve characterization and risk stratification in
      these patients.

PMID- 21855282
TI  - Does body weight impact the efficacy of vasopressin therapy in the management of
      septic shock?
AB  - BACKGROUND: Vasopressors used for the management of septic shock are often dosed
      according to body weight. Use of vasopressin for physiologic replacement in
      patients with septic shock is usually administered as a standard non-weight-based
      dose. We hypothesized that the efficacy of vasopressin may be influenced by body
      weight. PURPOSE: The primary objective was to determine if the effects of
      vasopressin on other vasopressor dosing requirements is related to body weight.
      Secondary objectives included evaluation of blood pressure and heart rate after
      the start of vasopressin infusion. METHODS: A retrospective, cohort study in a
      large academic health center was conducted. Sixty-four adult inpatients with
      septic shock (26 medical intensive care unit and 38 surgical intensive care unit)
      who required vasopressor administration including vasopressin therapy were
      included. Dosing requirements of vasopressors were captured 1 hour before and
      during the hour of vasopressin initiation and 2 and 4 hours later. Other
      information collected during the study period included blood pressure, mean
      arterial pressure, and heart rate. RESULTS: Most of the patients (n = 61)
      received vasopressin at a dose of 0.04 U/min. Changes in vasopressor dosing were
      significantly correlated with weight-adjusted vasopressin at 2 hours (correlation
      coefficient = -0.36, P = .03) and 4 hours (correlation coefficient = -0.46, P <
      .001). Use of vasopressin was associated with significant increases in systolic
      blood pressure, diastolic blood pressure, and mean arterial pressure at each time
      point compared with baseline. CONCLUSIONS: Effects of vasopressin on
      catecholamine dosing requirements in the setting of septic shock may be
      influenced by body weight. Prospective studies are needed to examine weight-based
      dosing of vasopressin in this setting.

PMID- 21855283
TI  - Stress hyperglycemia may not be harmful in critically ill patients with sepsis.
AB  - BACKGROUND: Stress hyperglycemia (SH) is commonly seen in critically ill
      patients. It has been shown to be associated with adverse outcomes in some groups
      of patients. The effects of SH on critically ill patients with sepsis have not
      been well studied. We aimed to evaluate the effects of SH in critically ill
      patients with sepsis. METHODS: In this retrospective study, patients with sepsis
      admitted to intensive care unit (ICU) over a 5-year period were included.
      RESULTS: Of 297 patients, 204 (68.7%) had SH during the study period. The mean
      blood glucose level in patients with SH was 8.7 mmol/L compared with 5.9 mmol/L
      in those without SH (P < .05). There were no statistically significant
      differences in age; sex; sepsis severity; cardiovascular, respiratory, and renal
      comorbidities; requirement of mechanical ventilation; inotropes; and Acute
      Physiology, Age, and Chronic Health Evaluation III and Simplified Acute
      Physiology 2 scores on ICU admission. Intensive care unit mortality was
      significantly lower in patients who had SH. The median duration of ICU and
      hospital length of stay was longer in patients with SH. On logistic regression
      analysis, the presence of SH was associated with reduced ICU mortality. Subgroup
      analysis revealed SH to be protective in patients with septic shock. CONCLUSION:
      Stress hyperglycemia may not be harmful in critically ill patients with sepsis.
      Patients with SH had lower ICU mortality.

PMID- 21855284
TI  - A pilot clinical trial to evaluate a novel time-to-positivity assay to measure
      the effectiveness of antibiotic therapy for septic patients in intensive care.
AB  - PURPOSE: The purpose of the study was to investigate whether a novel assay of
      antibiotic efficacy could predict clinical outcome measures in septic patients in
      the intensive care unit (ICU). METHODS: A prospective, noninterventional clinical
      study was performed involving 48 adult patients with sepsis in a single adult
      general ICU, with measurement of the time-to-positivity (Tpos) at 2 time points
      (Tpos1, Tpos2). RESULTS: The mean length of stay for all patients was 14.1 days
      (range, 2-98; median, 10 days). There was no significant difference between the
      Tpos1-adequate and the Tpos1-inadequate patients in day 1 Sequential Organ
      Failure Assessment or Acute Physiology and Chronic Health Evaluation II scores.
      However, there were a significant difference for the length of stay in ICU, with
      median stay in the Tpos1-adequate group of 7.8 days compared with 14.4 days in
      the Tpos1-inadequate group (Mann-Whitney U test, P = .028), and a significant
      difference in the length of stay in hospital, with a median stay in the Tpos1
      adequate group of 13 days compared with 31 days in the Tpos1-inadequate group (P
      = .001). There was no statistical association between Tpos1 and 28-day survival
      (P > .05). The Tpos2 data added no further information. CONCLUSIONS: This pilot
      study provides preliminary evidence that measurement of Tpos1 24 hours after the
      initiation of antibiotic therapy is associated with ICU length of stay and might
      be of value as a surrogate marker of antibiotic activity.

PMID- 21855285
TI  - Risk factors for underuse of lung-protective ventilation in acute lung injury.
AB  - PURPOSE: We assessed factors associated with underuse of lung-protective
      ventilation (LPV) in patients with acute lung injury (ALI). METHODS: A secondary
      analysis of Acute Respiratory Distress Syndrome Clinical Trials Network trial
      data, 1999 to 2005, was conducted. Tidal volumes recorded before trial
      randomization were analyzed to determine receipt of LPV (tidal volume <= 6.5
      mL/kg of predicted body weight [PBW]). RESULTS: Of 1385 participants, 430 (31.2%)
      received LPV. Average tidal volume was 7.65 +/- 1.82 mL/kg PBW; measured tidal
      volumes were greater than "lung-protective" tidal volumes predicted by 6.5 mL/kg
      PBW (mean difference, 67 +/- 108 mL; P < .0001). Multivariate predictors of LPV
      underuse were older age (odds ratio [OR] per SD year, 1.18; 95% confidence
      interval [CI], 1.02-1.38), white race (OR, 1.40; 95% CI, 1.05-1.88), shorter
      stature (OR per SD centimeter, 0.55; 95% CI, 0.48-0.63), lower Simplified Acute
      Physiology II Score (OR per SD, 0.78; 95% CI, 0.67-0.92), lower lung injury score
      (OR per SD, 0.83; 95% CI, 0.70-0.95), decreased serum bicarbonate (OR per SD
      mmol/L, 0.83; 95% CI, 0.71-0.97), shorter preenrollment intensive care unit stay
      (OR per SD day, 0.84; 95% CI, 0.73-0.98), and use of non-volume-controlled
      ventilation (OR, 3.07; 95% CI, 1.78-5.27). Setting tidal volumes to 450 mL (men)
      or 350 mL (women) would provide LPV to 80% of patients with ALI. CONCLUSIONS:
      Simple interventions could substantially improve adherence with LPV among
      patients with ALI and warrant prospective study.

PMID- 21855286
TI  - Heparin-induced thrombocytopenia type II in a surgical intensive care unit.
AB  - PURPOSE: The aim of this study was to investigate the epidemiology of and outcome
      from heparin-induced thrombocytopenia type II (HIT) in surgical intensive care
      unit (ICU) patients. PATIENTS AND METHODS: All 13,948 patients admitted to a
      university hospital surgical ICU between January 2004 and March 2008 were
      included in this retrospective cohort study. RESULTS: Of 349 patients with a
      clinical suspicion of HIT, 88 patients had platelet factor 4/heparin antibodies
      using enzyme-linked immunosorbent assay. The prevalence and incidence of HIT were
      0.82% and 0.63%, respectively. The complication rate was 43.5%, and the ICU and
      hospital mortality rates were 23.9% and 33%, respectively. In a multivariable
      analysis, the nadir platelet count (odds ratio, 1.03; 95% confidence interval,
      1.01-1.05; P = .048) was the only factor independently associated with risk of
      death in these patients. In a nested matched case-control analysis, mortality
      rates were similar in patients with HIT and in the matched controls. However,
      complication rates were higher, and ICU and hospital lengths of stay were longer
      in patients with HIT compared with those of the control group. CONCLUSIONS: In
      this cohort of surgical ICU patients, HIT was associated with increased morbidity
      but not mortality rates compared with a nested matched control group. The nadir
      platelet count was independently associated with a higher risk of in hospital
      death in these patients.

PMID- 21855287
TI  - Ventricular dysfunction and dilation in severe sepsis and septic shock: relation
      to endothelial function and mortality.
AB  - PURPOSE: The aim of this study was to evaluate echocardiography-based indices of
      myocardial function and markers of vascular inflammation and endothelial
      dysfunction in the early phases of severe sepsis. MATERIAL AND METHODS: Forty
      five adult patients (67% women; age 51 +/- 18 years; Acute Physiology and Chronic
      Health Disease Classification System II score, 23 +/- 7) admitted to the
      intensive care unit up to 24 hours after fulfilling criteria for severe sepsis or
      septic shock were studied. Clinical, laboratorial (endothelin 1 [ET1], vascular
      cellular adhesion molecule 1), and echocardiographic data were collected within
      the first 24 hours and again 72 hours and 7 days after admission. RESULTS:
      Intrahospital mortality was 33% (15 deaths). Left ventricular (LV) dysfunction
      (LV ejection fraction <55%) was identified in 15 (33%) patients, whereas right
      ventricular (RV) dysfunction (RV tissue Doppler peak systolic velocity [RV-Sm]
      <12 cm/s) was present in 14 (30%) patients. LogET1 was increased in patients with
      LV dysfunction (2.3 +/- 0.6 vs 1.8 +/- 0.4 pg/mL; P = .01) and RV dysfunction
      (2.5 +/- 0.5 vs 1.8 +/- 0.4 pg/mL; P < .001) and had negative correlations with
      LV ejection fraction (r = -0.50; P = .002) and RV-Sm (r = -0.67; P < .001). Left
      ventricular end-diastolic diameter, RV-Sm, and diastolic dysfunction were able to
      discriminate survivors from nonsurvivors, and the combination of these parameters
      identified groups of very low and high risk. CONCLUSION: Both LV and RV systolic
      dysfunctions are prevalent in severe sepsis, being directly associated with
      markers of endothelial dysfunction. Left ventricular nondilation, RV dysfunction,
      and diastolic dysfunction seem related to poor prognosis in this scenario.

PMID- 21855288
TI  - Early serum levels of soluble triggering receptor expressed on myeloid cells-1 in
      septic patients: correlation with monocyte gene expression.
AB  - PURPOSE: To define early kinetics of soluble triggering receptor expressed on
      myeloid cells-1 (sTREM-1) and of TREM-1 monocyte gene expression in critically
      ill patients with sepsis. METHODS: Blood was sampled at regular time intervals
      from 105 patients with sepsis. Concentrations of tumour necrosis factor alpha
      (TNFalpha), interleukin (IL)-6, IL-8 and IL-10 and IL-12p70 and sTREM-1 were
      measured by an enzyme immunoassay. Blood mononuclear cells were isolated on day 0
      from 20 patients and 10 healthy volunteers; RNA was extracted and gene expression
      of TREM-1 and TNFalpha were assessed by reverse transcriptase polymerase chain
      reaction. RESULTS: Early serum concentrations of sTREM-1 were greater among
      patients with severe sepsis/shock than among patients with sepsis; those of
      TNFalpha, IL-6, IL-8 and IL-10 were pronounced among patients with septic shock.
      Gene transcripts of TNFalpha were lower among patients with severe sepsis/shock
      than among patients with sepsis; that was not the case for TREM-1. Early serum
      levels of sTREM-1 greater than 180 pg/mL were predictors of shorter duration of
      mechanical ventilation. CONCLUSIONS: Although serum levels of sTREM-1 are
      increased early upon advent of severe sepsis/shock, gene expression of TREM-1 on
      monocytes in severe sepsis/shock is not increased. These findings add
      considerably to our knowledge on the pathophysiology of sepsis.

PMID- 21855290
TI  - Introduction: ECCC-IPACCMS-WFSICCM 2011 Annual Meeting Third Asia-Africa World
      Federation Societies Intensive and Critical Care Medicine Conference.

PMID- 21855289
TI  - The effects of levosimendan vs dobutamine added to dopamine on liver functions
      assessed with noninvasive liver function monitoring in patients with septic
      shock.
AB  - BACKGROUND: Septic shock is the leading causes of death in intensive care units.
      In addition to generous fluid administration, inotropic agents are commonly used
      to improve cardiac output. The effects of inotropic agents on regional blood flow
      remains unknown. OBJECTIVE: The aim of this study was to assess the effects of
      levosimendan vs dobutamine added to dopamine on liver functions assessed using
      noninvasive liver function monitoring (LiMON) in patients with septic shock.
      DESIGN: Prospective analysis. MEASUREMENTS AND RESULTS: We analyzed 30 patients
      with septic shock who were treated in an intensive care unit. Indocyanine green
      plasma disappearance rate (ICG-PDR) was conducted concurrently using the LiMON
      system. A dose of 0.3 mg/kg ICG was given through a cubital fossa vein as a
      bolus. RESULTS: Statistical analysis showed that the variation of hemodynamic
      variables was different between groups. In our results, the increase in systolic
      blood pressure, diastolic blood pressure, and mean arterial pressure was
      significantly higher in levosimendan group than in dobutamine group (P < .05).
      There was a decrease in before- and after-infusion ICG-PDR values in dobutamine
      group (20.38 +/- 4.83 vs 20.34 +/- 5.30), and no statistical difference was
      detected (P = .649). There was an increase in before- and after-infusion ICG-PDR
      values in levosimendan group (18.70 +/- 2.59 vs 21.65 +/- 3.20), and a
      statistical difference was detected (P = .001). There was statistical difference
      between groups (P = .000). CONCLUSION: These results suggest that levosimendan
      added to dopamine improves systemic hemodynamics and increases splanchnic
      perfusion assessed using the user-friendly noninvasive bedside system LiMON in
      patients with septic shock compared with dobutamine.

PMID- 21855291
TI  - The role of acceptance in rehabilitation in life-threatening illness.
AB  - CONTEXT: Palliative care rehabilitation aims to maximize physical and
      psychological functioning, but negative thoughts can hinder patients from
      attempting this approach. Acceptance and commitment therapy (ACT), a modified
      form of cognitive behavioral therapy, encourages individuals to experience and
      manage negative emotions by focusing on changing individual behavior and so
      improve functioning. ACT has been used in many health-related behavioral
      interventions but not in palliative care rehabilitation. OBJECTIVES: To
      investigate the relationship between acceptance (often called experiential
      acceptance in ACT) and psychological and physical status. METHODS: Cross
      sectional study in which a consecutive sample of patients attending a specialist
      palliative care day therapy unit for rehabilitation completed the Acceptance and
      Action Questionnaire-II to measure acceptance and the Kessler-10 questionnaire to
      measure psychological morbidity. Physical function was assessed by a timed two
      minute walking test and one-minute sit-to-stand test. Correlation statistics and
      multivariable regression analyses were used to explore the strength of
      relationships between acceptance and psychological morbidity and physical
      function. RESULTS: One hundred one patients were recruited, mainly white women
      with a mean age of 64 years. Correlation analysis showed a negative association
      between acceptance and psychological morbidity (r=-0.59) and a positive
      association between acceptance and sit to stand (r=0.27) and distance walked
      (r=0.21). All three of these relationships were statistically significant after
      adjustment. CONCLUSION: These associations suggest that it may be possible to
      reduce psychological morbidity and improve physical mobility by increasing
      patients' acceptance using an ACT-based intervention. Future work is now needed
      to develop an ACT-based intervention in palliative care rehabilitation and test
      its acceptability and feasibility.

PMID- 21855292
TI  - Developmental milestones in toddlers with atypical development.
AB  - The attainment of developmental milestones was examined and compared in 162
      infants and toddlers with developmental disabilities, including Down Syndrome (n
      = 26), Cerebral Palsy (n = 19), Global Developmental Delay (n = 22), Premature
      birth (n = 66), and Seizure Disorder (n = 29). Toddlers in the Seizures Disorder
      group began crawling at a significantly younger age than toddlers in the Down
      Syndrome and Cerebral Palsy groups. Additionally, toddlers in the Seizure
      Disorder group began walking at a younger age than children in the Down Syndrome,
      Cerebral Palsy, and Global Developmental Delay groups, while toddlers in the
      Prematurity group began walking at a younger age than children in the Down
      Syndrome group. No between group differences were found with respect to age at
      which first words were spoken. Results and their implications are discussed.

PMID- 21855293
TI  - Global asymptotic stability to a generalized Cohen-Grossberg BAM neural networks
      of neutral type delays.
AB  - In this paper, we first discuss the existence of a unique equilibrium point of a
      generalized Cohen-Grossberg BAM neural networks of neutral type delays by means
      of the Homeomorphism theory and inequality technique. Then, by applying the
      existence result of an equilibrium point and constructing a Lyapunov functional,
      we study the global asymptotic stability of the equilibrium solution to the above
      Cohen-Grossberg BAM neural networks of neutral type. In our results, the
      hypothesis for boundedness in the existing paper, which discussed Cohen-Grossberg
      neural networks of neutral type on the activation functions, are removed.
      Finally, we give an example to demonstrate the validity of our global asymptotic
      stability result for the above neural networks.

PMID- 21855294
TI  - Job stress among nurses in China.
AB  - Job stress is a well-known situation for nurses, especially for those working in
      the clinical environment. The purpose of this descriptive study was to examine
      the job stress level and stressors among nurses in a Zhuhai hospital. Ninety
      three nurses were recruited for the study. Findings were that nurses had a
      relatively high level of stress, with "Working Environment and Resources" and
      "Workload and Time" identified as the major stressors. This study provided
      preliminary insights on relieving job stress among nurses in China.

PMID- 21855295
TI  - Shortcomings of the ESRA-C acceptability study.

PMID- 21855296
TI  - Long-term monitoring of the ketogenic diet: Do's and Don'ts.
AB  - The ketogenic diet (KD) is an effective treatment for epilepsy and like other
      treatments it is not without side effects. The side effects encountered are
      related to the diet composition and the radical metabolic changes that results
      from a high fat, low carbohydrate and protein diet. Short-term side effects are
      well documented. Long-term side effects are not as well documented but since the
      last "international symposium on dietary therapies for epilepsy and other
      neurological disorders", there are now more prospective and longitudinal data.
      Monitoring practices and treatments will be discussed and compared to the
      International Ketogenic Diet Consensus Statement (IKDCS) from 2008.

PMID- 21855297
TI  - Preictal changes in cerebral haemodynamics: review of findings and insights from
      intracerebral EEG.
AB  - The possibility of recording changes in brain signals occurring before epileptic
      seizures is of considerable interest, both as markers for seizure anticipation
      and as a window into the mechanisms of seizure generation. Several studies have
      reported preictal changes on electrophysiological traces. More recently,
      observations have been made of changes occurring on haemodynamic signals before
      interictal events or before seizures, often without concurrent changes observed
      on electrophysiology. We present here a critical review of these findings, in
      optical imaging, SPECT and fMRI, followed by a discussion based on data from
      intracerebral EEG.

PMID- 21855298
TI  - Triheptanoin--a medium chain triglyceride with odd chain fatty acids: a new
      anaplerotic anticonvulsant treatment?
AB  - The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil
      used to treat rare metabolic disorders in USA and France. Heptanoate is
      metabolized by beta-oxidation to provide propionyl-CoA, which after carboxylation
      can produce succinyl-CoA, resulting in anaplerosis - the refilling of the
      tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the C5
      ketones, beta-ketopentanoate and/or beta-hydroxypentanoate, which are released
      into the blood and thought to enter the brain via monocarboxylate transporters.
      Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant
      in acute and chronic mouse seizures models. However, current knowledge on
      alterations of brain metabolism after triheptanoin administration and anaplerosis
      via propionyl-CoA carboxylation in the brain is limited. This review outlines
      triheptanoin's unique anticonvulsant profile and its clinical potential for the
      treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach
      for the treatment of epilepsy is discussed. More research is needed to elucidate
      the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential
      for the treatment of epilepsy and other disorders of the brain.

PMID- 21855300
TI  - New investigations of technical rhodium and iridium catalysts in homogeneous
      phase employing para-hydrogen induced polarization.
AB  - It is shown that the para-hydrogen induced polarization (PHIP) phenomenon in
      homogenous solution containing the substrate styrene is also observable employing
      simple inorganic systems of the form MCl(3).xH(2)O (M=Rh, Ir) as catalyst. Such
      observation confirms that already very simple metal complexes enable the creation
      of PHIP signal enhancement in solution. This opens up new pathways to increase
      the sensitivity of NMR and MRT by PHIP enhancement using cost-effective catalysts
      and will be essential for further mechanistic studies of simple transition metal
      systems.

PMID- 21855299
TI  - Polarizing agents and mechanisms for high-field dynamic nuclear polarization of
      frozen dielectric solids.
AB  - This article provides an overview of polarizing mechanisms involved in high
      frequency dynamic nuclear polarization (DNP) of frozen biological samples at
      temperatures maintained using liquid nitrogen, compatible with contemporary magic
      angle spinning (MAS) nuclear magnetic resonance (NMR). Typical DNP experiments
      require unpaired electrons that are usually exogenous in samples via paramagnetic
      doping with polarizing agents. Thus, the resulting nuclear polarization mechanism
      depends on the electron and nuclear spin interactions induced by the paramagnetic
      species. The Overhauser Effect (OE) DNP, which relies on time-dependent spin-spin
      interactions, is excluded from our discussion due the lack of conducting
      electrons in frozen aqueous solutions containing biological entities. DNP of
      particular interest to us relies primarily on time-independent, spin-spin
      interactions for significant electron-nucleus polarization transfer through
      mechanisms such as the Solid Effect (SE), the Cross Effect (CE) or Thermal Mixing
      (TM), involving one, two or multiple electron spins, respectively. Derived from
      monomeric radicals initially used in high-field DNP experiments, bi- or multiple
      radical polarizing agents facilitate CE/TM to generate significant NMR signal
      enhancements in dielectric solids at low temperatures (<100 K). For example,
      large DNP enhancements (~300 times at 5 T) from a biologically compatible
      biradical, 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL), have enabled
      high-resolution MAS NMR in sample systems existing in submicron domains or
      embedded in larger biomolecular complexes. The scope of this review is focused on
      recently developed DNP polarizing agents for high-field applications and leads up
      to future developments per the CE DNP mechanism. Because DNP experiments are
      feasible with a solid-state microwave source when performed at <20K, nuclear
      polarization using lower microwave power (<100 mW) is possible by forcing a high
      proportion of biradicals to fulfill the frequency matching condition of CE (two
      EPR frequencies separated by the NMR frequency) using the strategies involving
      hetero-radical moieties and/or molecular alignment. In addition, the combination
      of an excited triplet and a stable radical might provide alternative DNP
      mechanisms without the microwave requirement.

PMID- 21855301
TI  - Functional artificial free-standing yeast biofilms.
AB  - Here we report fabrication of artificial free-standing yeast biofilms built using
      sacrificial calcium carbonate-coated templates and layer-by-layer assembly of
      extracellular matrix-mimicking polyelectrolyte multilayers. The free-standing
      biofilms are freely floating multilayered films of oppositely charged
      polyelectrolytes and live cells incorporated in the polyelectrolyte layers. Such
      biofilms were initially formed on glass substrates of circular and ribbon-like
      shapes coated with thin layers of calcium carbonate microparticles. The templates
      were then coated with cationic and anionic polyelectrolytes to produce a
      supporting multilayered thin film. Then the yeast alone or mixed with various
      micro- and nanoparticle inclusions was deposited onto the multilayer composite
      films and further coated with outer polyelectrolyte multilayers. To detach the
      biofilms from the glass substrates the calcium carbonate layer was chemically
      dissolved yielding free-standing composite biofilms. These artificial biofilms to
      a certain degree mimic the primitive multicellular and colonial species. We have
      demonstrated the added functionality of the free-standing artificial biofilms
      containing magnetic, latex and silver micro- and nanoparticles. We have also
      developed "symbiotic" multicellular biofilms containing yeast and bacteria. This
      approach for fabrication of free-standing artificial biofilms can be potentially
      helpful in development of artificial colonial microorganisms composed of several
      different unicellular species and an important tool for growing cell cultures
      free of supporting substrates.

PMID- 21855302
TI  - Interaction of a "nido"-ruthenium terpyridylamine complex with charged elongated
      micellar scaffolds.
AB  - Influence on ionic surfactants by a specially designed terpyridylamine ligand and
      the ruthenium(II) complex formed with it has been studied in aqueous solution.
      The ligand coordinates to Ru(2+) into an octahedral geometry in such a way that
      the final form takes a "nido" or nest-like structure. The substitution on the
      pyridinyl moiety is kept at the ortho position to acquire the specified geometry.
      Similar complexes have been reported to have anti-tumor properties and thus the
      ruthenium complexes can effectively replace platinum complexes that serve the
      same purpose but with certain drawbacks. The "nido" geometry was chosen to
      minimize the cytotoxicity that creeps in when para substituents of the pyridinyl
      moiety are used. The latter variety forms a dendridic scaffold. In presence of
      both the ligand and the complex, ionic surfactants form elongated aggregates. The
      surface charge of those aggregates decides the nature of interaction of the
      ligand and the complex formed therefore. Interaction with anionic surfactant
      scaffold is found to be stronger than the cationic one.

PMID- 21855303
TI  - Expression of ornithine decarboxylase during the transport of saquinavir across
      the blood-brain barrier using composite polymeric nanocarriers under an
      electromagnetic field.
AB  - The expression of human ornithine decarboxylase (ODC) and permeability of
      saquinavir (SQV) across the blood-brain barrier were studied using nanoparticles
      (NPs) composed of poly(lactide-co-glycolide) (PLGA), poly-(gamma-glutamic acid)
      (gamma-PGA), and polyethyleneimine (PEI). SQV was encapsulated in the particle
      core to traverse a monolayer of human brain-microvascular endothelial cells
      (HBMECs) with the regulation of human astrocytes under an electromagnetic field
      (EMF). An increase in the weight percentage of PEI enhanced the particle size,
      zeta potential, and permeability of SQV. However, the viability of HBMECs reduced
      when the weight percentage of PEI increased. In addition, an increment in the
      molecular weight of gamma-PGA enhanced the particle size and viability of HBMECs,
      and reduced the zeta potential. The permeability of SQV and expression of ODC
      were in the order: an EMF with amplitude modulation (AM)>an EMF with frequency
      modulation>no EMF. At 0.04% PEI, the AM EMF increased 2.38 times the uptake of
      NPs and 2.72 times the expression of ODC. The combination of PEI/gamma-PGA/PLGA
      NPs and EMF can be an innovative strategy for delivering SQV into the brain.

PMID- 21855304
TI  - Protein delivery based on uncoated and chitosan-coated mesoporous silicon
      microparticles.
AB  - Mesoporous silicon is a biocompatible, biodegradable material that is receiving
      increased attention for pharmaceutical applications due to its extensive specific
      surface. This feature enables to load a variety of drugs in mesoporous silicon
      devices by simple adsorption-based procedures. In this work, we have addressed
      the fabrication and characterization of two new mesoporous silicon devices
      prepared by electrochemistry and intended for protein delivery, namely: (i)
      mesoporous silicon microparticles and (ii) chitosan-coated mesoporous silicon
      microparticles. Both carriers were investigated for their capacity to load a
      therapeutic protein (insulin) and a model antigen (bovine serum albumin) by
      adsorption. Our results show that mesoporous silicon microparticles prepared by
      electrochemical methods present moderate affinity for insulin and high affinity
      for albumin. However, mesoporous silicon presents an extensive capacity to load
      both proteins, leading to systems were protein could represent the major mass
      fraction of the formulation. The possibility to form a chitosan coating on the
      microparticles surface was confirmed both qualitatively by atomic force
      microscopy and quantitatively by a colorimetric method. Mesoporous silicon
      microparticles with mean pore size of 35 nm released the loaded insulin quickly,
      but not instantaneously. This profile could be slowed to a certain extent by the
      chitosan coating modification. With their high protein loading, their capacity to
      provide a controlled release of insulin over a period of 60-90 min, and the
      potential mucoadhesive effect of the chitosan coating, these composite devices
      comprise several features that render them interesting candidates as transmucosal
      protein delivery systems.

PMID- 21855305
TI  - Description of Leptopharynx brasiliensis nov. spec. and Leptopharynx costatus
      gonohymen nov. subspec. (Ciliophora, Microthoracida).
AB  - Using standard morphological methods, we describe one new Leptopharynx species
      and a new subspecies of L. costatus, both from soil of the neotropic region.
      Further, we studied two populations of L. costatus costatus. Leptopharynx
      brasiliensis nov. spec., which was discovered in the Mato Grosso, Brazil, is a
      large member (60MUm) of the genus with an enormous oral basket. It differs from
      similar congeners in having six monokinetids in kinety 6, widely spaced kinetids
      in kinety 1, and an average of 294 kinetids. Leptopharynx costatus gonohymen nov.
      subspec., which was discovered in southern Florida, makes a small (35MUm) and a
      large morph (55MUm) both with narrow oral basket. The small morph is inseparable
      from the small morph of L. costatus costatus, while the large morph has right
      angled adoral membranelles and widely (vs. narrowly) spaced kinetids in kinety 1.
      The small morphs of a Brazilian and an Austrian L. costatus match Mexican and
      other European populations, all having on average 181-187 kinetids. As yet, we
      know four morphs of L. costatus that differ by body size (small vs. large), the
      oral basket (narrow vs. wide), membranelle 1 (present vs. absent), and the
      arrangement of the membranelles (flat vs. angled).

PMID- 21855306
TI  - Infraciliature of eight Triplumaria species (Ciliophora, Entodiniomorphida) from
      Asian elephants with the description of six new species.
AB  - Intestinal ciliates excreted in the feces of Asian elephants were surveyed.
      Fourteen species in the order Entodiniomorphida were detected. Nine Triplumaria
      species in the family Cycloposthiidae were found. Using the silver impregnation,
      two known species, T. antis and T. dvoinosi, were redescribed and six new
      species, T. sukuna n. sp., T. zuze n. sp., T. solea n. sp., T. suwako n. sp., T.
      fulgora n. sp., and T. harpagonis n. sp., were described. T. sukuna, T. zuze, T.
      solea, and T. suwako have the perivestibular polybrachykinety along the
      vestibular opening. The buccal infraciliary bands of T. suwako are similar to
      those of T. selenica found from elephants and the buccal infraciliary bands of T.
      sukuna, T. zuze, and T. solea are similar to those of T. grypoclunis described
      from rhinoceroses. T. antis, T. dvoinosi, T. fulgora, and T. harpagonis have the
      vestibular polybrachykinety extending down inside the vestibulum as found in
      rumen ciliates in the family Ophryoscolecidae. The caudalial ciliary zones of T.
      dvoinosi and T. fulgora were retractable as found in rumen ophryoscolecids.
      Raabena bella and Pseudoentodinium elephantis showed high composition values over
      30%. Ciliate densities in the three fecal samples were 0.15, 1.09, and
      2.07*10(4)/ml.

PMID- 21855307
TI  - Patterns of cholesterol metabolism: pathophysiological and therapeutic
      implications for dyslipidemias and the metabolic syndrome.
AB  - Investigating cholesterol metabolism, which derives from balancing cholesterol
      synthesis and absorption, opens new perspectives in the pathogenesis of
      dyslipidemias and the metabolic syndrome (MS). Cholesterol metabolism is studied
      by measuring plasma levels of campesterol, sitosterol and cholestanol, that is,
      plant sterols which are recognised as surrogate cholesterol-absorption markers
      and lathosterol or squalene, that is, cholesterol precursors, which are
      considered surrogate cholesterol-synthesis markers. This article presents current
      knowledge on cholesterol synthesis and absorption, as evaluated by means of
      cholesterol precursors and plant sterols, and discusses patterns of cholesterol
      balance in the main forms of primary hyperlipidaemia and MS. Understanding the
      mechanism(s) underlying these patterns of cholesterol synthesis and absorption
      will help to predict the response to hypolipidemic treatment, which can then be
      tailored to ensure the maximum clinical benefit for patients.

PMID- 21855308
TI  - Different susceptibility to 1-methyl-4-phenylpyridium (MPP(+))-induced nigro
      striatal dopaminergic cell loss between C57BL/6 and BALB/c mice is not related to
      the difference of monoamine oxidase-B (MAO-B).
AB  - Subcutaneous and intraperitoneal administrations of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) induce selective dopaminergic (DA-ergic) neuronal death
      in many animal species. After passing through the blood-brain barrier (BBB), MPTP
      is converted to 1-methy-4-phenylpiridinium (MPP(+)) by astrocytic monoamine
      oxidase-B (MAO-B). MPP(+) then induces the dopaminergic neuronal death. In mice,
      marked strain differences in the susceptibility to MPTP-injection have been
      reported. To clarify which factor(s) cause the strain differences, MPTP or MPP(+)
      was intracerebroventricularly (icv) injected into adult C57BL/6 (highly
      susceptible to MPTP) and BALB/c (resistant to MPTP) mice. The brain tissues
      including the striatum and substantia nigra pars compacta (SNpc) were examined
      immunohistochemically using an antibody to tyrosine hydrocyrase (TH). MPP(+)
      injected C57BL/6 mice showed a significant decrease in TH-immunopositive areas in
      the striatum at Day 3 post injection (p<0.01), and TH-positive cells in the SNpc
      at Days 1 and 3 (p<0.01), respectively, compared to saline-injected control mice.
      In addition, MPP(+)-injected BALB/c mice showed a significant decrease in TH
      positive areas in the striatum at Days 1 and 3, and SNpc TH-positive cells in the
      SNpc at Day 3, respectively (p<0.05). However, the decrease rates in the BALB/c
      mice were lower than that in C57BL/6 mice. MPTP-injected C57BL/6 mice, however,
      showed no lesions in the striatum and SNpc at Days 1 and 7 after icv injection.
      All the present findings indicate that factors other than MAO-B can influence the
      strain susceptibility between C57BL/6 and BALB/c mice after the conversion from
      MPTP to MPP(+).

PMID- 21855309
TI  - DNA in ancient bone - where is it located and how should we extract it?
AB  - Despite the widespread use of bones in ancient DNA (aDNA) studies, relatively
      little concrete information exists in regard to how the DNA in mineralised
      collagen degrades, or where it survives in the material's architecture. While, at
      the macrostructural level, physical exclusion of microbes and other external
      contaminants may be an important feature, and, at the ultrastructural level, the
      adsorption of DNA to hydroxyapatite and/or binding of DNA to Type I collagen may
      stabilise the DNA, the relative contribution of each, and what other factors may
      be relevant, are unclear. There is considerable variation in the quality of DNA
      retrieved from bones and teeth. This is in part due to various environmental
      factors such as temperature, proximity to free water or oxygen, pH, salt content,
      and exposure to radiation, all of which increase the rate of DNA decay. For
      example, bone specimens from sites at high latitudes usually yield better quality
      DNA than samples from temperate regions, which in turn yield better results than
      samples from tropical regions. However, this is not always the case, and rates of
      success of DNA recovery from apparently similar sites are often strikingly
      different. The question arises as to whether this may be due to post-collection
      preservation or just an artefact of the extraction methods used in these
      different studies? In an attempt to resolve these questions, we examine the
      efficacy of DNA extraction methods, and the quality and quantity of DNA recovered
      from both artificially degraded, and genuinely ancient, but well preserved,
      bones. In doing so we offer hypotheses relevant to the DNA degradation process
      itself, and to where and how the DNA is actually preserved in ancient bone.

PMID- 21855310
TI  - Short-term effects of air pollution from biomass burning in mucociliary clearance
      of Brazilian sugarcane cutters.
AB  - Nasal mucociliary system is the first line of defense of the upper airways and
      may be affected acutely by exposure to particulate matter (PM) from biomass
      burning. Several epidemiologic studies have demonstrated a consistent association
      between levels of air pollution from biomass burning with increases in
      hospitalization for respiratory diseases and mortality. To determine the acute
      effects of exposure to particulate matter from biomass burning in nasal
      mucociliary transport by saccharin transit time (STT) test, we studied thirty
      three non-smokers and twelve light smokers sugarcane cutters in two periods: pre
      harvest season and 4 h after harvest at the first day after biomass burning. Lung
      function, exhaled carbon monoxide (CO), nasal symptoms questionnaire and
      mucociliary clearance (MC) were assessed. Exhaled CO was increased in smokers
      compared to non-smokers but did not change significantly after harvest. In
      contrast, STT was similar between smokers and non-smokers and decreased
      significantly after harvest in both groups (p < 0.001). Exposure to PM from
      biomass burning did not influence nasal symptoms. Our results suggest that acute
      exposure to particulate matter from sugarcane burned affects mucociliary
      clearance in smokers and non-smokers workers in the absence of symptoms.

PMID- 21855311
TI  - Pathophysiology of airway hyperresponsiveness in patients with nasal polyposis.
AB  - BACKGROUND: It has been hypothesized that airway hyperresponsiveness (AHR) is
      characterized by sensitivity (strength of stimulus) and reactivity
      (responsiveness to stimulus); the latter could be the intrinsic characteristic of
      AHR. The underlying mechanisms leading to AHR could be 1) airway inflammation, 2)
      reduction of forces opposing bronchoconstriction, and 3) structural airway
      changes/geometric factors. OBJECTIVE: Our main objective was to assess the
      relationships between reactivity in patients with nasal polyposis and these three
      mechanisms using measurements of 1) bronchial and bronchiolar/alveolar NO, 2)
      bronchomotor response to deep inspiration, and 3) forced expiratory flows and an
      index of airway to lung size, i.e. FEF(25-75%)/FVC. METHODS: Patients underwent
      spirometry, multiple flow measurement of exhaled NO (corrected for axial
      diffusion), assessment of bronchomotor response to deep inspiration by forced
      oscillation technique and methacholine challenge allowing the calculation of
      reactivity (slope of the dose-response curve) and sensitivity (PD(10)). RESULTS:
      One hundred and thirty-two patients were prospectively enrolled of whom 71
      exhibited AHR. Airway reactivity was correlated with alveolar NO concentration
      (rho = 0.35; p = 0.017), with airflow limitation (FEF(25-75%): rho = -0.40; p =
      0.003) and with an index of airway size to lung size (FEF(25-75%)/FVC: rho = 
      0.38; p = 0.005), of which only alveolar NO remained the only independent factor
      in a stepwise multiple regression analysis (variance 25%). Airway sensitivity was
      not correlated with any pulmonary function or exhaled NO parameter. CONCLUSION:
      In patients with nasal polyposis, alveolar NO is associated with airway
      reactivity, suggesting that bronchiolar/alveolar lung inflammation may constitute
      one intrinsic characteristic of increased responsiveness.

PMID- 21855312
TI  - Substance use and recessions: what can be learned from economic analyses of
      alcohol?
AB  - In this paper, I conduct a review of the economics literature examining the
      relationship between alcohol use and the macro economy comparing methods,
      measures and findings. Like illicit drug consumption, the relationship between
      alcohol use and economic conditions is not entirely straightforward since there
      are various theoretical explanations for why they might be positively or
      negatively related. Empirical findings suggest that the relationship between
      drinking and the economy depends on the type of user and whether use is examined
      in developing or developed countries. In developed countries, heavy drinkers
      consume less in a downturn, while light drinkers consume more. This pro-cyclical
      relationship found for heavy drinking does not hold for developed countries where
      disposable income is low. The implications for researchers interested in
      understanding how illicit drug consumption varies with the business cycle are
      that they must be careful to consider differential responses across user types as
      well as expensive and inexpensive drugs.

PMID- 21855313
TI  - Multiple system modelling of waste management.
AB  - Due to increased environmental awareness, planning and performance of waste
      management has become more and more complex. Therefore waste management has early
      been subject to different types of modelling. Another field with long experience
      of modelling and systems perspective is energy systems. The two modelling
      traditions have developed side by side, but so far there are very few attempts to
      combine them. Waste management systems can be linked together with energy systems
      through incineration plants. The models for waste management can be modelled on a
      quite detailed level whereas surrounding systems are modelled in a more
      simplistic way. This is a problem, as previous studies have shown that
      assumptions on the surrounding system often tend to be important for the
      conclusions. In this paper it is shown how two models, one for the district
      heating system (MARTES) and another one for the waste management system (ORWARE),
      can be linked together. The strengths and weaknesses with model linking are
      discussed when compared to simplistic assumptions on effects in the energy and
      waste management systems. It is concluded that the linking of models will provide
      a more complete, correct and credible picture of the consequences of different
      simultaneous changes in the systems. The linking procedure is easy to perform and
      also leads to activation of project partners. However, the simulation procedure
      is a bit more complicated and calls for the ability to run both models.

PMID- 21855314
TI  - Controlled gating and electrical detection of single 50S ribosomal subunits
      through a solid-state nanopore in a microfluidic chip.
AB  - We describe analysis and control of 50S ribosomal subunits by a solid-state 45nm
      diameter nanopore incorporated in a microfluidic chip. When used as a resistive
      pulse sensor, translocation of single 50S subunits through the nanopore produces
      current blockades that have a linear dependence on applied voltage. Introduction
      of individual subunits into the fluidic channel shows a threshold behavior that
      allows controlled entry of individual 50S ribosomal subunits. The incorporation
      of nanopores into a larger optofluidic chip system opens possibilities for
      electrical and optical studies of single ribosomes in well-defined and rapidly
      variable chemical environments.

PMID- 21855315
TI  - Simply amplified electrochemical aptasensor of ochratoxin A based on exonuclease
      catalyzed target recycling.
AB  - A new "signal-on" aptasensor for ultrasensitive detection of Ochratoxin A (OTA)
      in wheat starch was developed based on exonuclease-catalyzed target recycling. To
      construct the aptasensor, a ferrocene (Fc) labeled probe DNA (S1) was immobilized
      on a gold electrode (GE) via Au-S bonding for the following hybridization with
      the complementary OTA aptamer, with the labeled Fc on S1 far from the GE surface.
      In the presence of analyte OTA, the formation of aptamer-OTA complex would result
      in not only the dissociation of aptamer from the double-strand DNA but also the
      transformation of the probe DNA into a hairpin structure. Subsequently, the OTA
      could be liberated from the aptamer-OTA complex for analyte recycling due to the
      employment of exonuclease, which is a single-stranded DNA specific exonuclease to
      selectively digest the appointed DNA (aptamer). Owing to the labeled Fc in close
      proximity to the electrode surface caused by the formation of the hairpin DNA and
      to the analyte recycling, differential pulse voltammetry (DPV) signal could be
      produced with enhanced signal amplification. Based on this strategy, an
      ultrasensitive aptasensor for the detection of OTA could be exhibited with a wide
      linear range of 0.005-10.0ngmL(-1) with a low detection limit (LOD) of 1.0pgmL(
      1) OTA (at 3sigma). The fabricated biosensor was then applied for the measurement
      of OTA in real wheat starch sample and validated by ELISA method.

PMID- 21855316
TI  - Nano polyurethane-assisted ultrasensitive biodetection of H(2)O(2) over
      immobilized microperoxidase-11.
AB  - Nanostructured polyurethane (PU) synthesized by an emulsion polymerization with
      narrow size distribution was employed for the first time directly as a novel
      matrix for enzyme immobilization to develop sensitively amperometric biosensors.
      When Microperoxidase-11 (MP-11) was selected as a model protein, the resulting
      hydrogen peroxide (H(2)O(2)) biosensor exhibited improved sensitivity of
      29.6MUAmM(-1)cm(-2) with quite good response time of (1.3+/-0.4)s and remarkable
      limit of detection as low as 10pM (S/N 3) over existing protocols. A linear
      calibration curve for hydrogen peroxide was obtained up to 1.3MUM under the
      optimized conditions with a relative low calculated Michaelis-Menten constant
      (K(M)(app)) (1.87+/-0.05)MUM, which indicated the enhanced enzymatic affinity of
      MP-11 to H(2)O(2) via PU. The possible interferents had negligible effect on the
      response current and time of the prepared biosensor. Results suggest that the PU
      nanoparticles (PU-NPs) with good biocompatibility and sufficient interfacial
      adhesion hold promise as an attractive support material for construction of
      ultrasensitive amperometric biosensor.

PMID- 21855317
TI  - Au-nanocluster emission based glucose sensing.
AB  - Fabrication of a glucose biosensor based on Au-cluster emission quenching in the
      UV region is reported. The glucose biosensor is highly sensitive to beta-d
      glucose in 2.5-25.0mM range as confirmed from a linear calibration plot between
      Au-cluster colloid emission intensity as a function of beta-d-glucose
      concentration. The interaction of beta-d-glucose with l-cysteine capped Au
      cluster colloids has been confirmed from their Fourier transformed infrared
      spectroscopy (FTIR) measurements. It has been found that the biomolecules present
      in the serum such as ascorbic and uric acids, proteins and peptides do not
      interfere and affect in glucose estimation as confirmed from their absorption and
      fluorescence (FL) emission measurements. Practical utility of this sensor based
      on FL quenching method has been demonstrated by estimating the glucose level in
      human serum that includes diabetes and the data were found to be comparable or
      more accurate than those of the pathological data obtained from a local hospital.
      In addition, this biosensor is useful to detect glucose level over a wide range
      with sensor response time of the order of nano to picoseconds that is emission
      lifetime of Au clusters.

PMID- 21855318
TI  - Ultrasensitive signal-on DNA biosensor based on nicking endonuclease assisted
      electrochemistry signal amplification.
AB  - Combining the advantages of signal-on strategy and nicking endonuclease assisted
      electrochemistry signal amplification (NEAESA), a new sensitive and signal-on
      electrochemical DNA biosensor for the sequence specific DNA detection based on
      NEAESA has been developed for the first time. A Hairpin-shape probe (HP),
      containing the target DNA recognition sequence, is thiol-modified at 5' end and
      immobilized on gold electrode via Au-S bonding. Subsequently, the HP modified
      electrode is hybridized with target DNA to form a duplex. Then the nicking
      endonuclease is added and nicks the HP strand in the duplex. After nicking, 3'
      ferrocene (Fc)-labeled part complementary probe (Fc-PCP) is introduced on the
      electrode surface by hybridizing with the thiol-modified HP fragment, which
      results in the generation of electrochemical signal. Hence, the DNA biosensor is
      constructed successfully. The present DNA biosensor shows a wide linear range of
      5.0*10(-13)-5.0*10(-8)M for detecting target DNA, with a low detection limit of
      0.167pM. The proposed strategy does not require any amplifying labels (enzymes,
      DNAzymes, nanoparticles, etc.) for biorecognition events, which avoids false
      positive results to occur frequently. Moreover, the strategy has the benefits of
      simple preparation, convenient operation, good selectivity, and high sensitivity.
      With the advantages mentioned above, this simple and sensitive strategy has the
      potential to be integrated in portable, low cost and simplified devices for
      diagnostic applications.

PMID- 21855319
TI  - Morphology of sustentaculum tali: Biomechanical importance and correlation with
      angular dimensions of the talus.
AB  - SUMMARY OF BACKGROUND DATA: The talus and the calcaneus share the bulk of load
      transmitted from the leg to the skeleton of the foot. The present study analyses
      the inter-relationship between the superior articular surface and the angular
      dimensions of the talus with the morphology of the sustentaculum tali. OBJECTIVE:
      Identification of possible relationships between different angular parameters of
      the talus morphology and the sustentaculum tali in context of load transmission
      through the foot. METHODS: One articular surface and three angular parameters at
      the junction of the head and the body were measured from dried human talar bones.
      Corresponding calcaneal samples were measured for four dimensions at the
      sustentaculum tali. Correlation and regression statistical values between
      parameters were worked out and analysed. RESULTS: Several parameters within the
      talus demonstrated significant correlations amongst themselves. The neck vertical
      angle showed a strong correlation with the articulating surface area below the
      head of the talus. CONCLUSIONS: The inter-relationship between articular and
      angular parameters within the talus demonstrates strong correlation for certain
      parameters. Data presented in the study may be helpful to adjust calcaneal and
      talar screw placement techniques, prosthesis designing and bio-mechanical studies
      at this important region.

PMID- 21855321
TI  - Analysis of prognostic factors in patients with multiple recurrences of papillary
      thyroid carcinoma.
AB  - PURPOSE: Numerous studies in the past have mentioned various factors that
      influence the recurrence of papillary thyroid carcinoma, including age, tumor
      size, advanced stage, extrathyroidal extension, and distant metastasis, and
      attempts have been made to classify the disease into low-risk and high-risk group
      based on these clinicopathological factors. However, there has been relatively
      scarce study on patients with multiple recurrent papillary thyroid carcinoma.
      This study analyzed the risk factors associated with such cases. MATERIALS AND
      METHODS: This study investigated various clinicopathological factors of 416
      patients who were diagnosed with papillary thyroid carcinoma and received primary
      surgery at Yonsei University Wonju College of Medicine, Department of Surgery,
      from January 1983 to December 2006 and were followed up until October 2010. An
      investigation of factors associated with patients showing multiple recurrences
      was made. RESULTS: Patients were divided into 3 groups: group 1 (no recurrence,
      n=380), group 2 (1 recurrence only, n=21), and group 3 (multiple recurrences,
      n=15). The univariate analysis on risk factors revealed tumor size greater than 2
      cm, multifocality, clinical apparent lymph node metastasis to be risk factors
      associated with multiple recurrences of papillary thyroid carcinoma. A
      multivariate analysis performed on variables selected from univariate analysis
      demonstrated no significant risk factor. The 10-year disease-specific survival
      for 3 different patient groups (group 1, 2, and 3) was 100%, 100%, and 83.1%,
      respectively, and patients in more clinically advanced group demonstrated poorer
      prognosis (p<0.001). The 10-year overall survival rate for the 3 patient groups
      was 93.9%, 100%, and 92%, respectively, and clinically advanced groups tended to
      show poorer overall survival rate as well (p=0.046). DISCUSSION: A more
      aggressive and extensive surgery, as well as closer follow up, is to be required
      when operating on patients with tumor size greater than 2 cm, multifocality,
      clinical apparent lymph node metastasis. The use of imaging modalities, such as
      ultrasonography and PET-CT scan, may be desirable when monitoring such patients.

PMID- 21855320
TI  - Specificity and randomness: structure-function relationships in neural circuits.
AB  - A fundamental but unsolved problem in neuroscience is how connections between
      neurons might underlie information processing in central circuits. Building
      wiring diagrams of neural networks may accelerate our understanding of how they
      compute. But even if we had wiring diagrams, it is critical to know what neurons
      in a circuit are doing: their physiology. In both the retina and cerebral cortex,
      a great deal is known about topographic specificity, such as lamination and cell
      type specificity of connections. Little, however, is known about connections as
      they relate to function. Here, we review how advances in functional imaging and
      electron microscopy have recently allowed the examination of relationships
      between sensory physiology and synaptic connections in cortical and retinal
      circuits.

PMID- 21855322
TI  - 11alpha-Hydroxylation of 16alpha,17-epoxyprogesterone by Rhizopus nigricans in a
      biphasic ionic liquid aqueous system.
AB  - 11alpha-Hydroxylation of 16alpha,17-epoxyprogesterone (EP) by Rhizopus nigricans
      is an essential step in the synthesis of many steroidal drugs, while low
      conversion of the biohydroxylation is a tough problem to be solved urgently in
      industry. Two ionic liquids (ILs) of [BMIm][PF(6)] and [BMIm][NTf(2)] were used
      in the biotransformation of EP by R. nigricans. The results indicated that the
      conversion carried out in [BMIm][PF(6)]-aqueous biphasic system was greatly
      increased to above 90% at 18 g/L feeding concentration. A simplified mechanism
      was proposed to explain the improvement of the bioconversion in a biphasic ionic
      liquid aqueous system. Besides, successive three batches of bioconversion were
      carried out in the biphasic system with a total conversion of 87% at phase ratio
      10 and 75% at phase ratio 5, respectively. Since recycling of the [BMIm][PF(6)]
      is quite easy, there is a great potential for the application of ILs in fungi
      biotransformation to implement green production.

PMID- 21855323
TI  - Electroactive mixed culture derived biofilms in microbial bioelectrochemical
      systems: the role of pH on biofilm formation, performance and composition.
AB  - The pH-value played a crucial role for the development and current production of
      anodic microbial electroactive biofilms. It was demonstrated that only a narrow
      pH-window, ranging from pH 6 to 9, was suitable for growth and operation of
      biofilms derived from pH-neutral wastewater. Any stronger deviation from pH
      neutral conditions led to a substantial decrease in the biofilm performance.
      Thus, average current densities of 151, 821 and 730 MUA cm(-2) were measured for
      anode biofilms grown and operated at pH 6, 7 and 9 respectively. The microbial
      diversity of the anode chamber community during the biofilm selection process was
      studied using the low cost method flow-cytometry. Thereby, it was demonstrated
      that the pH value as well as the microbial inocula had an impact on the resulting
      anode community structure. As shown by cyclic voltammetry the electron transfer
      thermodynamics of the biofilms was strongly depending on the solution's pH-value.

PMID- 21855324
TI  - Milox fractionation of empty fruit bunches from Elaeis guineensis.
AB  - Milox pulping of EFB was used to obtain pulps. In the first Milox stage, the
      influences of operating variables on pulp properties were studied and polynomial
      and neural fuzzy models that reproduced the experimental results with errors less
      than 10% were developed. Operating variables were found (93 wt.% of formic acid,
      3 wt.% of hydrogen peroxide, and 165 min) that yielded acceptable pulp properties
      (40.5% yield, 50.3% brightness and 608 mL/g viscosity) at reasonable chemical and
      energy costs. The second stage was studied by subjecting the liquors of the
      previously optimized first stage to different treatment times. This time should
      be 30 min or less, to avoid a negative effect on viscosity. The residual liquor
      from the first Milox stage contained virtually no precipitable lignin and only
      low amounts of sugar (wt.%): glucose 0.71, xylose 4.22, galactose 1.19, mannose
      0.22, all on original raw material dry.

PMID- 21855325
TI  - Evaluation of the biological stability of waste during landfill stabilization by
      thermogravimetric analysis and Fourier transform infrared spectroscopy.
AB  - This study seeks to assess the biological stability of landfilled municipal solid
      waste (MSW) based on the changes in organic matter, as revealed by
      thermogravimetric analysis and Fourier transform infrared (FTIR) spectroscopy.
      Derivate thermogravimetry profiles (DTG) showed a reduction in peak intensity at
      200-350  degrees C (DTG2), while an increase in peak intensity and a shift
      towards higher temperature at 400-600  degrees C (DTG3). The decrease in the peak
      intensity of the aliphatic methylene at 2920 and 2850 cm(-1), and the increase of
      aromatic substances and polysaccharide at 1640 cm(-1) in the FTIR spectra also
      confirm the changes. Well-fitted correlations of the peak intensity ratio
      (2920/1640) and peak area ratio (DTG2/DTG3) to C/N ratio were also established,
      confirming that the 2920/1640 and the DTG2/DTG3 ratios can be considered as
      reliable parameters for tracking the biological stability of MSW during landfill
      stabilization.

PMID- 21855326
TI  - Techno-economic comparison of a biological hydrogen process and a 2nd generation
      ethanol process using barley straw as feedstock.
AB  - A process combining dark fermentation and photofermentation for production of
      hydrogen is interesting due to its potential of producing hydrogen at a high
      yields. In this study, the hydrogen process is compared to a 2nd generation
      ethanol process with respect to cost and with the aim of increasing our
      understanding of the pros and cons and giving a clear picture of the present
      status of the two processes. The hydrogen production cost was found to be about
      20 times higher than the ethanol production cost, 421.7 ?/GJ compared to 19.5
      ?/GJ. The main drawbacks of the hydrogen process are its low productivity, low
      energy efficiency, and the high cost of buffer and base required to control the
      pH.

PMID- 21855327
TI  - A detailed one-dimensional model of combustion of a woody biomass particle.
AB  - A detailed one-dimensional model for combustion of a single biomass particle is
      presented. It accounts for particle heating up, pyrolysis, char gasification and
      oxidation and gas phase reactions within and in the vicinity of the particle. The
      biomass pyrolysis is assumed to take place through three competing reactions
      yielding char, light gas and tar. The model is validated using different sets of
      experiments reported in the literature. Special emphasis is placed on examination
      of the effects of pyrolysis kinetic constants and gas phase reactions on the
      combustion process which have not been thoroughly discussed in previous works. It
      is shown that depending on the process condition and reactor temperature, correct
      selection of the pyrolysis kinetic data is a necessary step for simulation of
      biomass particle conversion. The computer program developed for the purpose of
      this study enables one to get a deeper insight into the biomass particle
      combustion process.

PMID- 21855328
TI  - Recent progress in electrodes for microbial fuel cells.
AB  - The performance and cost of electrodes are the most important aspects in the
      design of microbial fuel cell (MFC) reactors. A wide range of electrode materials
      and configurations have been tested and developed in recent years to improve MFC
      performance and lower material cost. As well, anodic electrode surface
      modifications have been widely used to improve bacterial adhesion and electron
      transfer from bacteria to the electrode surface. In this paper, a review of
      recent advances in electrode material and a configuration of both the anode and
      cathode in MFCs are provided. The advantages and drawbacks of these electrodes,
      in terms of their conductivity, surface properties, biocompatibility, and cost
      are analyzed, and the modification methods for the anodic electrode are
      summarized. Finally, to achieve improvements and the commercial use of MFCs, the
      challenges and prospects of future electrode development are briefly discussed.

PMID- 21855329
TI  - Ethanesulfonic acid-based esterification of industrial acidic crude palm oil for
      biodiesel production.
AB  - An industrial grade acidic crude palm oil (ACPO) pre-treatment process was
      carried out using ethanesulfonic acid (ESA) as a catalyst in the esterification
      reaction. ESA was used in different dosages to reduce free fatty acid (FFA) to a
      minimum level for the second stage of biodiesel production via alkaline
      transesterification reaction. Different process operating conditions were
      optimized such as ESA dosage (0.25-3.5% wt/wt), methanol to ACPO molar ratio (1:1
      20:1), reaction temperature (40-70  degrees C), and reaction time (3-150 min).
      This study revealed the potential use of abundant quantities of ACPO from oil
      palm mills for biodiesel production. The lab scale results showed the
      effectiveness of the pre-treatment process using ESA catalyst. Three consecutive
      catalyst recycling runs were achieved without significant degradation in its
      performance. Second and third reuse runs needed more reaction time to achieve the
      target level of FFA content. Esterification and transesterification using ESA and
      KOH respectively is proposed for biodiesel industrial scale production. The
      produced biodiesel meets the international standards specifications for biodiesel
      fuel (EN 14214 and ASTM D6751).

PMID- 21855330
TI  - Purification and biochemical characterization of a moderately halotolerant NADPH
      dependent xylose reductase from Debaryomyces nepalensis NCYC 3413.
AB  - A Xylose reductase (XR) from the halotolerant yeast, Debaryomyces nepalensis NCYC
      3413 was purified to apparent homogeneity. The enzyme has a molecular mass of 74
      kDa with monomeric subunit of 36.4 kDa (MALDI-TOF/MS) and pI of 6.0. The enzyme
      exhibited its maximum activity at pH 7.0 and 45  degrees C (21.2U/mg). In situ
      gel digestion and peptide mass fingerprinting analysis showed 12-22% sequence
      homology with XR from other yeasts. Inhibition of the enzyme by DEPC
      (diethylpyrocarbonate) confirmed the presence of histidine residue in its active
      site. The enzyme exhibited high preference for pentoses over hexoses with greater
      catalytic efficiency for arabinose than xylose. The enzyme also showed absolute
      specificity with NADPH over NADH. The enzyme retained 90% activity with 100 mM of
      NaCl or KCl and 40% activity with 1 M KCl which suggest that the enzyme is
      moderately halotolerant and can be utilized for commercial production of xylitol
      under conditions where salts are present.

PMID- 21855331
TI  - Enhanced chrysene degradation by halotolerant Achromobacter xylosoxidans using
      Response Surface Methodology.
AB  - Degradation of chrysene, a four ring High Molecular Weight (HMW) Polycyclic
      Aromatic Hydrocarbon (PAH) is of intense environmental interest, being
      carcinogenic, teratogenic and mutagenic. Multiple PAH degrading halotolerant
      Achromobacter xylosoxidans was isolated from crude oil polluted saline site.
      Response Surface Methodology (RSM) using Central Composite Design (CCD) of
      Bushnell-Haas medium components was successfully employed for optimization
      resulting 40.79% chrysene degradation on 4th day. The interactions between
      variables as chrysene and glucose concentrations, pH and inoculum size on
      degradation were examined by RSM. Under optimum conditions, A. xylosoxidans
      exhibited 85.96% chrysene degradation on 5th day. The optimum values predicted by
      RSM were confirmed through confirmatory experiments. It was also noted that pH
      and glucose as co-substrate play a dynamic role in enhancement of chrysene
      degradation. Hence, A. xylosoxidans can be further used for subsequent microcosm
      and in situ experiments for its potential to remediate PAH contaminated saline
      and non-saline soils.

PMID- 21855332
TI  - Synthesis of methyl esters from palm (Elaeis guineensis) oil using cobalt doped
      MgO as solid oxide catalyst.
AB  - The potential of Mg(x)Co(2-)(x)O(2) as heterogeneous reusable catalyst in
      transesterification of palm oil to methyl ester was investigated. The catalyst
      was prepared via co-precipitation of the metal hydroxides at different Mg-Co
      ratios. Mg(1.7)Co(0.3)O(2) catalyst was more active than Mg(0.3)Co(1.7)O(2) in
      the transesterification of palm oil with methanol. The catalysts calcined at
      temperature 300  degrees C for 4 h resulted in highly active oxides and the
      highest transesterification of 90% was achieved at methanol/oil molar ratio of
      9:1, catalyst loading of 5.00 wt.%, reaction temperature of 150  degrees C and
      reaction time of 2 h. The catalyst could easily be removed from reaction mixture,
      but showed 50% decrease in activity when reused due to leaching of active sites.

PMID- 21855333
TI  - Ursolic acid is a PPAR-alpha agonist that regulates hepatic lipid metabolism.
AB  - In this study, we confirmed that ursolic acid, a plant triterpenoid, activates
      peroxisome proliferator-activated receptor (PPAR)-alpha in vitro. Surface plasmon
      resonance and time-resolved fluorescence resonance energy transfer analyses do
      not show direct binding of ursolic acid to the ligand-binding domain of PPAR
      alpha; however, ursolic acid enhances the binding of PPAR-alpha to the peroxisome
      proliferator response element in PPAR-alpha-responsive genes, alters the
      expression of key genes in lipid metabolism, significantly reducing intracellular
      triglyceride and cholesterol concentrations in hepatocytes. Thus, ursolic acid is
      a PPAR-alpha agonist that regulates the expression of lipid metabolism genes, but
      it is not a direct ligand of PPAR-alpha.

PMID- 21855334
TI  - Simple synthetic toll-like receptor 2 ligands.
AB  - Stimulation of toll-like receptor 2 (TLR2) by bacterial lipoproteins induces fast
      non-specific immune responses against pathogens followed by slow but specific
      adaptive immune responses. Development of synthetic TLR2 agonists/antagonists
      would be useful in the prevention of different infectious and immunologic
      disorders. The current study reports synthesis and TLR2 activity of two simple
      TLR2 ligands, which feature minimal structural requirement for TLR2 activity (two
      long lipid chains) and stimulate agonistic activity at nanomolar concentration.

PMID- 21855335
TI  - Discovery of novel imidazo[1,2-a]pyrazin-8-amines as Brk/PTK6 inhibitors.
AB  - A series of substituted imidazo[1,2-a]pyrazin-8-amines were discovered as novel
      breast tumor kinase (Brk)/protein tyrosine kinase 6 (PTK6) inhibitors. Tool
      compounds with low-nanomolar Brk inhibition activity, high selectivity towards
      other kinases and desirable DMPK properties were achieved to enable the
      exploration of Brk as an oncology target.

PMID- 21855336
TI  - Synthesis and evaluation of ferrocenoyl pentapeptide (Fc-KLVFF) as an inhibitor
      of Alzheimer's Abeta1-42 fibril formation in vitro.
AB  - Aggregation and fibril formation of beta-amyloid peptides (Abeta) is the key
      event in the pathogenesis of Alzheimer's disease. Many efforts have been made on
      the development of effective inhibitors to prevent Abeta fibril formation or
      disassemble the preformed Abeta fibrils. Peptide inhibitors with sequences
      homologous to the hydrophobic segments of Abeta can alter the aggregation pathway
      of Abeta, together with decrease of the cell toxicity. In this study, the
      conjugate of ferrocenoyl (Fc) with pentapeptide KLVFF (Fc-KLVFF), was synthesized
      by HBTU/HOBt protocol in solution. The inhibitory effect of Fc-KLVFF on Abeta(1
      42) fibril formation was evaluated by thioflavin T fluorescence assay, and
      confirmed by atomic force microscopy (AFM) and transmission electron microscopy
      (TEM) analyses. Fc-KLVFF shows high inhibitory effect towards the fibril
      formation of Abeta(1-42). Additionally, the attachment of ferrocenoyl moiety onto
      peptides allows us to investigate the interaction between the inhibitor and
      Abeta(1-42) in real-time by electrochemical method. As expected, tethering of
      ferrocenoyl moiety onto pentapeptide shows improved lipophilicity and significant
      resistance towards proteolytic degradation compared to its parent peptide.

PMID- 21855338
TI  - Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of
      cytochrome P450 activities.
AB  - The pyrrole based N6022 was recently identified as a potent, selective,
      reversible, and efficacious S-nitrosoglutathione reductase (GSNOR) inhibitor and
      is currently undergoing clinical development for the treatment of acute asthma.
      GSNOR is a member of the alcohol dehydrogenase family (ADH) and regulates the
      levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione
      (GSNO). Reduced levels of GSNO, as well as other nitrosothiols (SNOs), have been
      implicated in the pathogenesis of many diseases including those of the
      respiratory, cardiovascular, and gastrointestinal systems. Preservation of
      endogenous SNOs through GSNOR inhibition presents a novel therapeutic approach
      with broad applicability. We describe here the synthesis and structure-activity
      relationships (SAR) of novel pyrrole based analogues of N6022 focusing on removal
      of cytochrome P450 inhibition activities. We identified potent and novel GSNOR
      inhibitors having reduced CYP inhibition activities and demonstrated efficacy in
      a mouse ovalbumin (OVA) model of asthma.

PMID- 21855337
TI  - Design and evaluation of a novel fluorescent CB2 ligand as probe for receptor
      visualization in immune cells.
AB  - Cannabinoid CB2 receptor has emerged as a very promising target over the last
      decades. We have synthesized and evaluated a new fluorescent probe designated
      NMP6 based on 6-methoxyisatin scaffold, which exhibited selectivity and K(i)
      value at hCB2 of 387 nM. We have demonstrated its ability to be an effective
      probe for visualization of CB2 receptor binding using confocal microscopy and a
      flow cytometry probe for the analysis of CB2 protein expression. Furthermore,
      NMP6 was easily obtained in two chemical steps from commercially available
      building blocks.

PMID- 21855339
TI  - Metal-free cleavage efficiency toward DNA by a novel PNA analog-bridged
      macrocyclic polyamine.
AB  - In this report we describe the synthesis of a new class of cyclen-contained
      compounds with novel peptide nucleic acid (PNA) analog motif. Target bis-cyclen
      derivative B was prepared and characterized by ESI-MS, NMR and HPLC. Interactions
      between compound B and calf thymus DNA were studied by thermal denaturation.
      Results indicate that the DNA binding affinity of B is stronger than that of mono
      cyclen compound A, and the binding ability is little affected by the change of
      ionic strength. Agarose and denaturing polyacrylamide gel electrophoresis were
      used to assess the DNA cleavage activities. The macrocyclic polyamine-PNA analog
      conjugate B as a nuclease model can effectively cleave DNA via an oxidative
      pathway at micromolar concentration (10 MUM) without the use of any additional
      metal ions. Meanwhile, the mono-cyclen compound A shows nearly no DNA cleavage
      effect under the same conditions.

PMID- 21855340
TI  - Solid-phase synthesis and pharmacological evaluation of novel nucleoside-tethered
      dinuclear platinum(II) complexes.
AB  - Three novel inosine-based dinuclear platinum complexes have been synthesized via
      a solid-phase strategy. In these compounds, the metal is linked both to the N-7
      of the purine nucleus and to the terminal amine group of a hexylamine side chain
      installed on N-1. Cis- or trans- diamine as well as ethylenediamine ligands are
      coordinated to platinum along with a chloride. The synthesised complexes were
      tested against four different human tumor cell lines. One of these complexes
      proved to be more cytotoxic than cisplatin against the MCF7 cancer cell line in a
      short-term exposure assay.

PMID- 21855341
TI  - Heat shock protein families 70 and 90 in Duchenne muscular dystrophy and
      inflammatory myopathy: balancing muscle protection and destruction.
AB  - Heat shock proteins are important factors in skeletal muscle physiology and
      stress response. We examined the effects of chronic inflammation on the
      distribution of heat shock protein families 70 and 90 using immunofluorescence
      and Western blotting, in muscle biopsies from 33 idiopathic inflammatory myopathy
      patients [aged 26-66 (dermatomyositis), 17-78 (polymyositis) and 57-80 (sporadic
      inclusion body myositis) years], and seven Duchenne muscular dystrophy patients
      (aged 3-19 years). Our results reveal the multifaceted role played by chaperones
      in inflammatory muscle tissue. On the one hand, regenerating, atrophic and
      vacuolated muscle fibers displayed upregulation of both protein families. Higher
      levels of chaperones in challenged fibers point to the myocyte's attempt to
      restore and regenerate. On the other hand, heat shock proteins of the 90 family
      were strongly upregulated in macrophages and cytotoxic T-cells actively invading
      nonnecrotic muscle fibers of sporadic inclusion body myositis and polymyositis,
      probably conferring enhanced myocytotoxic capacity. Our data provide positive
      arguments for exploring heat shock protein 90-based therapy in inflammatory
      muscle disease.

PMID- 21855342
TI  - Relationship between body mass index and preoperative treatment response to
      aromatase inhibitor exemestane in postmenopausal patients with primary breast
      cancer.
AB  - BACKGROUND: Some studies have shown that high body mass index (BMI) is associated
      with inferior outcome after adjuvant therapy with anastrozole in breast cancer
      patients. We aimed to investigate predictive effect of BMI on clinical response
      to neoadjuvant therapy with exemestane in postmenopausal patients with primary
      breast cancer. PATIENTS AND METHODS: The study group consisted of 109 patients
      from the JFMC 34-0601 neoadjuvant endocrine therapy trial. Patients were
      categorized into three groups according to BMI: low (BMI < 22 kg/m(2)),
      intermediate (22 <= BMI < 25 kg/m(2)) and high (BMI >= 25 kg/m(2)). Statistical
      analyses were performed to explore the predictive effect of BMI on clinical
      response. RESULTS: Higher BMI correlated with positive progesterone receptor
      status (p < 0.01) and low Ki-67 index (p = 0.03). Objective response rates (ORR)
      were 21.7% in low BMI, 56.0% in intermediate BMI and 60.6% in high BMI,
      respectively (p = 0.01). In a multivariate analysis, low BMI was an independent
      negative predictor of clinical response. CONCLUSION: Low BMI was associated with
      a decreased ORR to neoadjuvant endocrine therapy with exemestane. Our results may
      suggest that the predictive effect of BMI varies according to the type of
      aromatase inhibitor and objective outcome.

PMID- 21855343
TI  - Comparative study of spatial localization of HER-2 and CEP17 signals and of HER
      2/CEP17 ratios, in "thin" and "thick" tissue sections.
AB  - One presumed drawback of performing fluorescence in situ hybridization on routine
      tissue sections for HER-2 status evaluation in breast carcinomas is nuclear
      truncation. Therefore, HER-2/CEP 17 ratios were compared in routine (4 MUm) vs.
      thicker (15 MUm) tissue sections. Additionally, the distances of both signals
      from the nuclear center were measured by three-dimensional image analysis. HER-2
      and CEP 17 signals' number increased in thick sections; however, HER-2/CEP 17
      ratios were decreased. This could be attributed to a preferential increase in
      CEP17 signals explained by their more peripheral localization and apparent "loss"
      in truncated nuclei. The aforementioned decrease of HER-2 ratios did not alter
      HER-2 status except in cases in the equivocal category where it changed from
      equivocal to non-amplified. Thus, at least a subset of the equivocal cases could
      represent an artifactual increase of HER-2 ratio related to nuclear truncation
      and loss of peripheral CEP 17 signals in routine sections.

PMID- 21855344
TI  - Evaluation of the pressure-redistributing properties of prefabricated foot
      orthoses in older people after at least 12 months of wear.
AB  - Foot problems are highly prevalent in older people. To treat such problems in
      this age-group prefabricated ('off-the-shelf') foot orthoses are frequently
      prescribed. However, such devices are susceptible to material compression and
      deformation, which may reduce their effectiveness over time. Therefore, the aim
      of this study was to compare the pressure-redistributing properties of new
      prefabricated orthoses to orthoses worn for at least 12 months. Thirty-one adults
      (10 males, 21 females) aged over 65 years (mean 75.4, SD 5.2) participated.
      Plantar pressure data were collected under the rearfoot, midfoot and forefoot
      using the Pedar((r)) in-shoe system while participants walked along an 8m walkway
      wearing shoes only, new orthoses and old orthoses (orthoses were full length,
      dual-density prefabricated FormthoticTM devices). Compared to the shoe-only
      condition, both the new and old orthoses produced significant reductions in peak
      pressure and maximum force in the rearfoot with corresponding increases in force
      and contact area in the midfoot. Compared to the new orthoses, the old orthoses
      exhibited small but significant increases in peak pressure in the rearfoot (6%,
      p=0.001) and maximum force in the rearfoot (5%, p<0.001) and forefoot (2%,
      p=0.032). These findings indicate that the prefabricated orthoses evaluated in
      this study are only slightly less effective at redistributing plantar pressure
      after at least 12 months of wear.

PMID- 21855345
TI  - Postural sway during quiet standing is related to physiological tremor and muscle
      volume in young and elderly adults.
AB  - To examine the age-related deterioration in postural control, we investigated the
      association between postural sway during quiet standing and either amplitude of
      physiological tremor or muscle volume of the plantar flexors in 20 young and 20
      elderly adults. They maintained a quiet standing position on a force platform for
      60s with their eyes open or closed. During quiet standing, physiological tremors
      detected using a piezoresistive accelerometer were recorded from the soleus
      muscle, and the center of pressure (COP) displacement and body acceleration in
      the antero-posterior direction were calculated using the ground reaction forces
      as an assessment of postural sway. Muscle volume was predicted from muscle
      thickness by an ultrasonographic image. The physiological tremor of the soleus
      muscle during quiet standing was significantly greater in elderly than in young
      adults, and a positive association between physiological tremor and the amplitude
      of postural sway was found for young and elderly adults combined. Furthermore,
      physiological tremor was positively correlated with the high-frequency component
      of COP sway during quiet standing. A significantly negative relation between the
      muscle volume of the plantar flexors and postural sway was found in both age
      groups. These results suggest that physiological tremor reflects high-frequency
      fluctuations in postural sway during quiet standing in young and elderly adults,
      and age-related increases in the postural sway amplitude in the antero-posterior
      direction may be related to a decrease in muscle volume of the plantar flexors
      for maintaining an upright posture.

PMID- 21855347
TI  - Virus-host interactomes and global models of virus-infected cells.
AB  - Novel high-throughput technologies such as yeast two-hybrid and RNA interference
      (RNAi) screens provide the tools to study interactions between viral proteins and
      the host on a genomic scale. In this review, we provide an overview of studies in
      which these technologies were applied and of computational approaches for the
      analysis of the identified viral interactors in the context of the host cell. The
      results of these studies illustrate the advantages of integrative systems biology
      approaches in the investigation of viral pathogens.

PMID- 21855346
TI  - Importance of Candida-bacterial polymicrobial biofilms in disease.
AB  - Candida albicans is the most prevalent human fungal pathogen, with an ability to
      inhabit diverse host niches and cause disease in both immunocompetent and
      immunocompromised individuals. C. albicans also readily forms biofilms on
      indwelling medical devices and mucosal tissues, which serve as an infectious
      reservoir that is difficult to eradicate, and can lead to lethal systemic
      infections. Biofilm formation occurs within a complex milieu of host factors and
      other members of the human microbiota. Polymicrobial interactions will probably
      dictate the cellular and biochemical composition of the biofilm, as well as
      influence clinically relevant outcomes, such as drug and host resistance and
      virulence. In this manuscript, we review C. albicans infections in the context of
      in vivo polymicrobial biofilms and implications for pathogenesis.

PMID- 21855348
TI  - Biological membranes: the importance of molecular detail.
AB  - Are lipid interactions with membrane proteins best described in terms of the
      physical properties of the lipid bilayer or in terms of direct molecular
      interactions between particular lipid molecules and particular sites on a
      protein? A molecular interpretation is more challenging because it requires
      detailed knowledge of the 3D structure of a membrane protein, but recent studies
      have suggested that a molecular interpretation is necessary. Here, the idea is
      explored that lipid molecules modify the ways that transmembrane alpha-helices
      pack into bundles, by penetrating between the helices and by binding into clefts
      between the helices, and that these effects on helix packing will modulate the
      activity of a membrane protein.

PMID- 21855350
TI  - A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and
      pharmacophore model as Wnt2/beta-catenin pathway inhibitors in non-small-cell
      lung cancer cell lines.
AB  - We developed Wnt/beta-catenin inhibitors by identifying 13 number of 3
      arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to
      inhibit the Wnt/beta-catenin signal pathway and cancer cell proliferation. In the
      optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b]pyrazine
      core skeletons showed were shown to higher activity than 2,3,6-trisubstituted
      quinoxaline's and thus hold promise for use as potential small-molecule
      inhibitors of the Wnt/beta-catenin signal pathway in non-small-cell lung cancer
      cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound
      954, which presented the highest activity with a fit value of 2.81. The
      pharmacophore mapping for the compounds including 954, pyrido[2,3,-b]pyrazine
      core had hydrogen-bond acceptor site and hydrophobic center roles.

PMID- 21855349
TI  - Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa
      quorum sensing.
AB  - Quorum sensing (QS) is a population-dependent signaling process bacteria use to
      control multiple processes including virulence that is critical for establishing
      infection. The most common QS signaling molecule used by Gram-negative bacteria
      are acylhomoserine lactones. The development of non-native acylhomoserine lactone
      (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram
      negative bacteria. In this work, we have synthesized a set of optically pure
      gamma-lactams and their reduced cyclic azahemiacetal analogues, bearing the
      additional alkylthiomethyl substituent, and evaluated their effect on the AHL
      dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of
      these ligands and the simple structural modification such as the length of the
      alkylthio substituent has notable effect on activity. The gamma-lactam
      derivatives with nonylthio or dodecylthio chains acted as inhibitors of las
      signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio
      or hexylthio substituent was found to strongly inhibit both las and rhl signaling
      at higher concentrations while the propylthio analogue strongly stimulated the
      las QS system at lower concentrations.

PMID- 21855352
TI  - Synthesis and photobiological study of a novel chlorin photosensitizer BCPD-18MA
      for photodynamic therapy.
AB  - This paper reports synthesis and photobiological properties of a novel chlorin
      photosensitizer BCPD-18MA. Cytotoxicity, cellular uptake, subcellular location,
      biodistribution, photodynamic therapy (PDT) efficiency, cell apoptosis as well as
      histological analysis of the liposomal-delivered BCPD-18MA (L-BCPD-18MA) was
      studied using mammary adenocarcinoma MDA-MB-231 cells and Lewis lung carcinoma
      (LLC) implanted in C57BL/6 mice as experimental models. The results showed that L
      BCPD-18 was incorporated rapidly into MDA-MB-231 cells and localized partially in
      mitochondria. L-BCPD-18 induced cell apoptosis by PDT. In addition,
      biodistribution of L-BCPD-18MA in LLC-bearing mice demonstrated a fast clearance
      rate of the drug and good skin-related tumor selectivity. Finally, entrapment of
      BCPD-18 into liposomes resulted in a dramatic impairment of dark toxicity and a
      notable improvement of PDT antitumor efficacy in vitro. Compared with liposomal
      delivered BPDMA (L-BPDMA), L-BCPD-18MA exhibited low dark toxicity and high PDT
      efficiency on MDA-MB-231 cells. The photodynamic efficacy of L-BCPD-18MA on LLC
      bearing mice is comparable to that of L-BPDMA, implying that L-BCPD-18MA is a
      potential antitumor candidate for PDT.

PMID- 21855351
TI  - Synthesis and characterization of tritylthioethanamine derivatives with potent
      KSP inhibitory activity.
AB  - Assembly of a bipolar mitotic spindle requires the action of class 5 kinesins,
      and inhibition or depletion of this motor results in mitotic arrest and
      apoptosis. S-Trityl-l-cysteine is an allosteric inhibitor of vertebrate Kinesin
      Spindle Protein (KSP) that has generated considerable interest due to its anti
      cancer properties, however, poor pharmacological properties have limited the use
      of this compound. We have modified the triphenylmethyl and cysteine groups,
      guided by biochemical and cell-based assays, to yield new cysteinol and
      cysteamine derivatives with increased inhibitory activity, greater efficacy in
      model systems, and significantly enhanced potency against the NCI60 tumor panel.
      These results reveal a promising new class of conformationally-flexible small
      molecules as allosteric KSP inhibitors for use as research tools, with activities
      that provide impetus for further development as anti-tumor agents.

PMID- 21855353
TI  - Extended targeting potential and improved synthesis of Microcin C analogs as
      antibacterials.
AB  - Microcin C (McC) (1) is a potent antibacterial compound produced by some
      Escherichia coli strains. McC functions through a Trojan-Horse mechanism: it is
      actively taken up inside a sensitive cell through the function of the YejABEF
      transporter and then processed by cellular aminopeptidases. Processed McC (2) is
      a non-hydrolysable aspartyl-adenylate analog that inhibits aspartyl-tRNA
      synthetase (AspRS). A new synthesis is described that allows for the production
      of a wide variety of McC analogs in acceptable amounts. Using this synthesis a
      number of diverse compounds was synthesized with altered target specificity.
      Further characteristics of the YejABEF transporters were determined using these
      compounds.

PMID- 21855354
TI  - Design, synthesis, and biological evaluation of imidazoline derivatives as p53
      MDM2 binding inhibitors.
AB  - Three series of novel imidazoline derivatives were designed, synthesized, and
      evaluated for their p53-MDM2 binding inhibitory activities, and anti
      proliferation activities against PC3, A549, KB, and HCT116 cancer cell lines.
      Five of the tested compounds showed enhanced p53-MDM2 binding inhibitory potency
      and anti-proliferation activities in comparison with that of Nutlin-1. Flow
      cytometric analysis indicated that compound 7c, one of the most potent p53-MDM2
      binding inhibitors with a K(i) value of 0.6 MUM, showed its ability to arrest
      cell cycle progression.

PMID- 21855355
TI  - Synthesis and protective effects of aralkyl alcoholic 2-acetamido-2-deoxy-beta-D
      pyranosides on hypoglycemia and serum limitation induced apoptosis in PC12 cell.
AB  - Neuroprotective agents have been in the focus of attention in the treatment of
      ischemic stroke. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola
      rosea L., possessed a wide range of biological activities, especially
      neuroprotection. In an attempt to improve neuroprotective effects of new
      salidroside analogs for ischemic stroke, a series of novel aralkyl alcoholic 2
      acetamido-2-deoxy-beta-d-pyranosides were synthesized and their protective
      activities against the hypoglycemia and serum limitation induced cell death in
      rat pheochromocytoma cells (PC12 cells) were studied. Most compounds showed
      strong neuroprotective effects, especially for 4g and 4h, which exhibited a great
      potency superior to salidroside. MTT assay, Hoechst 33342 staining, and flow
      cytometry with annexin V/PI staining collectively showed that pretreatment with
      4g and 4h attenuated cell viability loss and apoptotic cell death in cultured
      PC12 cells. Caspase-3 colorimetric assay and Rhodamine 123 staining revealed the
      changes in expression levels of caspase-3 and mitochondrial membrane potential in
      PC12 cells on exposure to hypoglycemia and serum limitation with and without 4g
      and 4h pretreatment, respectively. All the results suggested that 4g and 4h
      protects the PC12 cells against hypoglycemia and serum limitation induced
      apoptosis possibly by modulation of apoptosis-related gene expression and
      restoration of the mitochondrial membrane potential. Therefore, these novel
      findings may provided a new framework for the design of new aralkyl alcoholic 2
      acetamido-2-deoxy-beta-d-pyranosides as neuroprotective agents for treating
      cerebral ischemic stroke and neurodegenerative diseases.

PMID- 21855356
TI  - Development and characterization of improved beta-lactone-based anti-virulence
      drugs targeting ClpP.
AB  - Here, we report the synthesis and in depth characterization of a second
      generation beta-lactone derived virulence inhibitors. Based on initial results
      that emphasized the intriguing possibility to disarm bacteria in their virulence
      the present study develops this concept further and analyses the potential of
      this strategy for drug development. We were able to expand the collection of
      bioactive compounds via an efficient synthetic route. Testing of all compounds
      revealed several hits with anti-virulence activity. Moreover, we demonstrated
      that these molecules act solely by reducing virulence but not killing bacteria
      which is an important prerequisite for preserving the useful microbiome. Finally,
      incubation of lactones with eukaryotic cell lines indicated a tolerable
      cytotoxicity which is essential for entering animal studies.

PMID- 21855357
TI  - Norcantharimide analogues possessing terminal phosphate esters and their anti
      cancer activity.
AB  - A family of norcantharidin analogues possessing a terminal alcohol (ethanol,
      propanol, butanol, pentanol, hexanol and cyclohexanol) moiety were treated with
      either chlorodiethyl, chlorodiphenyl or chloro-bis-trichloroethyl-phosphate to
      afford highly focused libraries of the corresponding phosphate esters. Subsequent
      biological screening against a panel of nine human cancer cell lines identified a
      trend between the ease of phosphate unmasking (phosphate ester hydrolysis) and
      cell death. The most potent analogues possessed either a diphenyl or a bis
      trichloroethyl moiety. The effect of alkyl spacer was also examined with the
      hexyl analogues typically more potent. 4-Aza-4-(3-{bis(2,2,2
      trichloroethyl)phosphate}propyl)-10-oxatricyclo[5.2.1.0]decane-3,5-dione (10b)
      was the most potent analogue synthesised with an average GI(50) of 11 MUM across
      a panel of nine human carcinoma cell lines: colon carcinoma (HT29 and SW480);
      breast carcinoma (MCF-7); ovarian carcinoma (A2780); lung carcinoma (H460); skin
      carcinoma (A431); prostate carcinoma (DU145); neuronal carcinoma (BE2-C) and
      brain carcinoma (SJ-G2). This represents a fivefold improvement in anti
      proliferative activity relative to the lead, norcantharidin.

PMID- 21855359
TI  - Important parameters to consider for the characterization of PET and SPECT
      imaging probes.

PMID- 21855358
TI  - Inhibition of LuxS by S-ribosylhomocysteine analogues containing a [4-aza]ribose
      ring.
AB  - LuxS (S-ribosylhomocysteinase) catalyzes the cleavage of the thioether linkage of
      S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3
      pentanedione (DPD), the precursor to a small signaling molecule that mediates
      interspecies bacterial communication called autoinducer 2 (AI-2). Inhibitors of
      LuxS should interfere with bacterial interspecies communication and potentially
      provide a novel class of antibacterial agents. In this work, SRH analogues
      containing substitution of a nitrogen atom for the endocyclic oxygen as well as
      various deoxyriboses were synthesized and evaluated for LuxS inhibition. Two of
      the [4-aza]SRH analogues showed modest competitive inhibition (K(I) ~40 MUM),
      while most of the others were inactive. One compound that contains a hemiaminal
      moiety exhibited time-dependent inhibition, consistent with enzyme-catalyzed ring
      opening and conversion into a more potent species (K(I)(*)=3.5 MUM). The
      structure-activity relationship of the designed inhibitors highlights the
      importance of both the homocysteine and ribose moieties for high-affinity binding
      to LuxS active site.

PMID- 21855360
TI  - Transcriptional profiling in cadmium-treated rice seedling roots using
      suppressive subtractive hybridization.
AB  - Cadmium (Cd), a non-essential metal, is a kind of toxic heavy metal to life,
      which can accumulate in rice tissues including seeds, thus posing a risk to human
      health through food chain. To investigate the molecular mechanisms of rice
      response to Cd exposure, suppression subtractive hybridization and mirror
      orientation selection were used to compare gene expression profiles in seedling
      roots of Cd-exposed and control (unexposed) rice plants (Oryza sativa L.,
      Nipponbare). Approximately 1700 positive clones, with insertions ranging from 250
      to 1300 bp, were identified through reverse cDNA microarray analysis. Gene
      expression was further confirmed by real time RT-PCR. A number of differentially
      expressed genes were found in Cd-exposed rice roots, including 28 up-regulated
      genes and 19 down-regulated genes. They were found to be involved in diverse
      biological processes, such as metabolism, stress response, ion transport and
      binding, protein structure and synthesis, as well as signal transduction. Notably
      a number of known functional genes were identified encoding membrane proteins and
      stress-related proteins such as heat shock proteins, monosaccharide transporters,
      CBL-interacting serine/threonine-protein kinases and metal tolerance proteins.
      The cDNAs isolated in this study contribute to our understanding of genes and the
      biochemical pathways that may play a key role in the response of plants to metal
      exposure in the environment.

PMID- 21855361
TI  - Sinonasal carcinoma associated with inverted papilloma: a report of 16 cases.
AB  - OBJECTIVES: To analyse the characteristics and outcome of patients with carcinoma
      associated with inverted papilloma, and find predictors of associated malignancy.
      METHODS: The medical records of 228 patients who were diagnosed with IP between
      January 1990 and December 2010 were retrospectively reviewed. Out of 228
      patients, 16 were also diagnosed with carcinoma. We evaluated their clinical
      characteristics, treatment modalities, and survival outcomes. RESULTS: The
      incidence of carcinoma associated with IP was 7.0%. Fourteen were synchronous
      carcinomas and two were metachronous. Tumours arising inside the frontal sinus or
      the frontoethmoidal recess were more likely to be associated with carcinoma.
      Patients who had a stage of T2 or less had a much better outcome than those who
      had a stage of T3 or greater (disease-free period, 84.8 months vs. 5.7 months,
      p<0.001). CONCLUSION: Tumours originating in the frontal sinus or frontoethmoidal
      recess have a tendency to be associated with carcinoma. As most (87.5%) of the
      carcinomas were diagnosed at the same time as the inverted papilloma, complete
      histological examination of the whole excised tumour is warranted because early
      diagnosis and treatment is essential as T2 and lower stage carcinomas had a
      strikingly better prognosis than T3 and higher stage carcinomas.

PMID- 21855362
TI  - Minimally invasive trans-mediastinal endoscopic approach to insert phrenic
      stimulation electrodes in the human diaphragm: a preliminary description in
      cadavers.
AB  - OBJECTIVE: Diaphragm pacing by phrenic nerve (PN) stimulation is currently used
      for patients with central respiratory paralysis to be weaned from mechanical
      ventilation. Electrodes are inserted either through bilateral thoracotomy or
      through four ports laparoscopy. The aim of this experimental work is to
      demonstrate the feasibility of trans-mediastinal bilateral implantation of PN
      electrodes using a flexible gastroscope introduced through a cervical incision in
      human cadavers. METHODS: Ten refrigerated and non-embalmed cadavers were used.
      The gastroscope was introduced through a cervical incision into the latero
      tracheal space and then subsequently into both pleura by opening the mediastinal
      pleura. After identification of the PN, electrodes were introduced through an
      intercostal space to the desired diaphragmatic location using a long, pliable
      needle with the electrode loaded in its lumen. RESULTS: Results are described for
      each hemi-diaphragm not for an anatomic subject. Mediastinal exploration and
      introduction of the video gastroscope into the pleural cavities proved easy in
      all subjects. Pleural adherences were present in five hemi-diaphragms. The
      central tendon of both hemi-diaphragms could be identified unambiguously in all
      the subjects. Identification of the entry point of the phrenic nerve into the
      diaphragm was straightforward in 10 hemi-diaphragms. In the remaining 10, this
      proved more difficult because of mediastinal fat or lung parenchyma. Introduction
      of the electrode-holding needles through the intercostal space and their
      insertion close to the phrenic nerve entry point was also easy. Withdrawal of the
      needle from the diaphragm and 'capture' of the hook were successful on the first
      attempt in 14 hemi-diaphragms, but failed in six others in whom a second attempt
      was necessary. CONCLUSION: Trans-mediastinal implantation of PN stimulation
      electrodes is possible using a flexible endoscope. This application of endoscopic
      surgery could allow a minimally invasive placement of PN electrodes in patients
      with central respiratory paralysis, for example, at the time of tracheostomy.

PMID- 21855363
TI  - False positive fixation of fluorodeoxyglucose positron emission tomography after
      correction of a vocal cord paralysis.

PMID- 21855364
TI  - A mathematical model for seasonal variability of vitamin D due to solar
      radiation.
AB  - It is widely recognized that vitamin D deficiency has detrimental health
      consequences. The ultraviolet (UV) B radiation increases the serum vitamin D
      level, expressed by 25-hydroxyvitamin-D(3) [25(OH)D]. An analytical model is
      presented to calculate the serum 25(OH)D changes throughout a year, caused by the
      solar exposure variability due to geophysical and habitual factors. The model is
      tuned by taking into account recent experimental results of serum 25(OH)D
      changes, after a series of artificial (by fluorescent tubes) UV exposures. The
      model uses the erythemal and vitamin D weighted irradiances, inferred from the
      Brewer spectrophotometer and the Kipp and Zonen broad-band meter measurements,
      carried out in Belsk (52 degrees N, 21 degrees E), Poland, in 2010. The modeled
      seasonal pattern of the serum 25(OH)D concentration in Polish indoor workers is
      only slightly different, than in subjects with typical outdoor activity habits,
      and in those with sun-seeking behavior. A deep minimum in the serum 25(OH)D
      concentration appears in late winter, regardless of outdoor activity habits. An
      extra sunbathing to boost the vitamin D level is not worth taking, because of a
      minor improvement of the vitamin D status, and because of a greater erythema
      risk. It would be much safer and more effective to maintain an adequate vitamin D
      level through diet supplements, even in summer, for non sun-seeking subjects.

PMID- 21855365
TI  - Regulation of gonadotropin-releasing hormone neurons by glucose.
AB  - Reproduction is influenced by energy balance, but the physiological pathways
      mediating their relationship have not been fully elucidated. As the central
      regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate
      numerous physiological signals, including metabolic cues. Circulating glucose
      levels regulate GnRH release and might in part mediate the effects of negative
      energy balance on fertility. Existing evidence suggests that neural pathways
      originating in the hindbrain, as well as in the hypothalamic feeding nuclei,
      transmit information concerning glucose availability to GnRH neurons. Here we
      review recent evidence suggesting that GnRH neurons might directly sense changes
      in glucose availability by a mechanism involving AMP-activated protein kinase.
      These findings expand our understanding of how metabolic signaling in the brain
      regulates reproduction.

PMID- 21855366
TI  - Lipocalin 2 regulation and its complex role in inflammation and cancer.
AB  - Lipocalin 2 is a protein that has garnered a great deal of interest in
      multidisciplinary fields over the last two decades since its discovery. However,
      its exact function in metabolic processes remains to be completely characterized.
      More recently, it has come to light as a highly upregulated protein in the
      setting of injury and infection. This review focuses on lipocalin 2 regulation
      and its relationship to cytokine and endocrine signaling pathways.

PMID- 21855367
TI  - Risk factors and consequences of atrial fibrillation with rapid ventricular
      response in patients with ischemic stroke treated with intravenous thrombolysis.
AB  - Atrial fibrillation (AF) is associated with rapid ventricular response (RVR) that
      increases myocardial demand and blood pressure instability. We investigated the
      incidence, risk factors, and outcomes of RVR among patients with ischemic stroke
      receiving treatment with intravenous (IV) recombinant tissue plasminogen
      activator (rtPA). Consecutive patients with AF who received IV rtPA within 3
      hours of symptom onset were included. Vascular risk factors, stroke
      characteristics, and outcome measures were compared between patients who
      developed RVR and those who did not. Eighty patients with AF (mean age, 79 years;
      46% men) who underwent rtPA treatment were studied. Nineteen (24%) of these
      patients developed RVR and were treated with IV rate-controlling medications. A
      bimodal pattern of distribution was observed in the occurrence of RVR, with the
      first peak occurring within 12 hours of stroke onset and the second peak
      occurring 24-48 hours after onset. Compared with the patients without RVR, those
      with RVR stayed a median duration of 1.2 days longer in the intensive care unit
      (P = .048). There were no differences in functional recovery and hemorrhagic
      outcomes between the patients with RVR and those without RVR. We observed a 16
      hour delay in the resumption of antiarrhythmic medications (either at previous or
      reduced dosage) in the patients who subsequently developed RVR (median time from
      stroke onset, 29 hours vs 13 hours; P = .040). Our findings suggest that a delay
      in the resumption of rate-control medications in patients with AF may result in
      RVR and prolong the use of intensive care resources.

PMID- 21855369
TI  - A population-based study of the prevalence and sociodemographic risk factors of
      self-reported epilepsy among adults in the United Kingdom.
AB  - BACKGROUND: Few studies have investigated the prevalence of self-reported
      epilepsy among adults in the United Kingdom and none has focused on identifying
      risk factors associated with epilepsy. METHODS: Data were obtained from the 2009
      British Household Panel Survey, a population-based cohort study of adults >= 16
      years of age residing in the United Kingdom (n=14,419). Cases were ascertained by
      identifying individuals who responded "yes" to having epilepsy. Prevalence rates
      were age- and sex-adjusted using mid-2009 population data and 95% confidence
      intervals (CI) were calculated. Logistic regression identified risk factors for
      self-reported epilepsy. RESULTS: A total of 112 individuals reported having
      epilepsy, resulting in a point prevalence of 8.6 per 1000 (95% CI: 6.6, 10.5).
      There were no differences in prevalence rates across strata of age, sex, marital
      status, employment status, employment satisfaction, academic or vocational
      qualifications, and socioeconomic status. Among males, the prevalence rate for
      the >75 age group was significantly lower compared to the 30-44 (p=0.0243) and 45
      59 age groups (p=0.0099). Individuals who were younger OR=0.91 (0.85, 0.98), not
      married OR=0.80 (0.67, 0.95), had less education OR=0.84 (0.74, 0.95), were less
      satisfied with their employment OR=0.66 (0.57, 0.77), and had lower income
      OR=0.87 (0.78, 0.98) were more likely to have epilepsy. CONCLUSIONS: The
      prevalence rates reported are similar to those described previously. The
      rationale for observing these specific risk factors for self-reported epilepsy
      are discussed in terms of public attitudes and stigma associated with epilepsy.

PMID- 21855368
TI  - Stroke and cardio-ankle vascular stiffness index.
AB  - BACKGROUND: We investigated the relationship between stroke and cardio-ankle
      vascular stiffness index (CAVI), a novel noninvasive measure of vascular
      stiffness. METHODS: Eighty-five patients with cerebrovascular disease who
      underwent CAVI were enrolled in the current study. They were 63 men and 22 women
      with a mean age of 70.0 +/- 10.8 years. They were divided into 4 groups according
      to neurologic abnormalities and magnetic resonance imaging (MRI) findings: 12
      with transient ischemic attack (TIA), 26 with white matter ischemic lesions
      (WMLs), 17 with large artery atherosclerosis, and 30 with small vessel occlusion.
      Eight hundred fifty-four healthy patients (487 men and 367 women; mean age 65.1
      +/- 9.4 years) served as controls. The results were stratified by gender and age
      and statistically analyzed using the Fisher, Bonferroni-Dunn, and Scheffe tests.
      RESULTS: The average of CAVI was as follows: control males 60 to 69 years of age,
      9.05 +/- 0.82 (as a representative value); TIA, 9.3 +/- 1.5; WML, 10.3 +/- 1.3;
      large artery atherosclerosis, 10.2 +/- 1.2; and small vessel occlusion, 10.0 +/-
      1.6, respectively. The difference in CAVI between each group and age- and gender
      matched controls was 0.492 for TIA (no statistical significance); WML, 0.733 (P <
      .001, and P = .002 Scheffe); large artery atherosclerosis, 0.838 (P < .001, and P
      = .005 Scheffe); and small vessel occlusion, 1.034 (P < .001), respectively.
      Linear regression analysis of CAVI and plaque score revealed a significant
      relationship in patients with ischemic cerebrovascular disease (P < .05).
      CONCLUSIONS: Compared with healthy control subjects, CAVI is statistically
      greater in patients with ischemic cerebrovascular diseases, particularly with
      WML, large artery atherosclerosis, and small vessel occlusion, but not in
      patients with TIA. CAVI had a clear relationship with carotid ultrasound plaque
      score. It appears that CAVI is a simple and noninvasive test for indicating
      atherosclerosis in patients with stroke.

PMID- 21855370
TI  - Introduction of QUIP (quality information program) as a semi-automated quality
      assessment endeavor allowing retrospective review of errors in cross-sectional
      abdominal imaging.
AB  - RATIONALE AND OBJECTIVES: The aims of this study were to review the role of a
      quality information program (QUIP) as a semiautomated educational feedback
      mechanism and to review common errors in cross-sectional abdominal and pelvic
      studies as an initiative for continuing medical education and improving patient
      care. MATERIALS AND METHODS: Abdominal and pelvic errors identified by QUIP and
      cases collected from morbidity and mortality conferences were reviewed. Errors
      were classified and graded to levels of morbidity. RESULTS: There were 222 errors
      in 218 patients over 4 years in this study. One hundred thirteen (51%) were
      identified after the introduction of QUIP (January to December 2009). One hundred
      thirty-eight studies (61%) were read independently, while 84 (39%) were double
      read. Sixty-five percent of errors (145 of 222) were false-negatives, of which 45
      (31%) were "satisfaction-of-search" errors. There were 62 cognitive errors (28%),
      nine technical errors (4%), eight communication errors (4%), six ordering errors
      (3%), and five false-positives identified. Seventy-six percent of errors were
      identified on computed tomography (n = 168); fewer cases involved ultrasound (n =
      20 [9%]) and magnetic resonance (n = 34 [15%]). Forty-one percent resulted in no
      changes to patient outcomes. Forty-percent caused minor patient morbidity, and
      19% caused major patient morbidity, including three cases (1%) that likely
      contributed to patient death. CONCLUSIONS: Most abdominopelvic errors in this
      study were classified as false-negatives. Many can be attributed to satisfaction
      of-search errors. Implementing a simple, semiautomated QUIP allows timely
      feedback regarding errors to radiologists. This may improve the quality of health
      care while allowing radiologists the opportunity to learn from each case they are
      involved in.

PMID- 21855371
TI  - What is the best treatment for primary infected aortic aneurysms?

PMID- 21855373
TI  - Evaluation of the usefulness of magnetic resonance imaging in the assessment of
      the thickness of the roof of the glenoid fossa of the temporomandibular joint.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of magnetic
      resonance imaging (MRI) in measuring thickness of the roof of the glenoid fossa
      (RGF) of the temporomandibular joint (TMJ). STUDY DESIGN: Minimum RGF thickness
      in 95 TMJs of 59 patients with temporomandibular disorders were measured and
      compared on both sagittal-section MRI and cone-beam computed tomography (CBCT).
      RGF thickness on MRI was also compared with MRI, CBCT, and arthrographic
      findings. RESULTS: Minimum RGF thickness was greater on MRI (1.46 mm) than on
      CBCT (0.90 mm). Spearman's correlation coefficient by rank for these 2 types of
      measurements was 0.63. RGF thickness on MRI differed significantly between those
      with and without degenerative joint changes (1.69 vs 1.32 mm; P < .01) and
      between those with and without disk displacement (1.58 vs 1.35 mm; P = .04), but
      showed no associations with disk deformity, joint effusion, or disk perforation.
      CONCLUSIONS: MRI is useful in measuring RGF thickness from diagnostic as well as
      radiation protection standpoints.

PMID- 21855374
TI  - The effect of previous conditioning exercise on diaphyseal and metaphyseal bone
      to imposition and withdrawal of training in young Thoroughbred horses.
AB  - This study recorded the response to training of the diaphysis of the proximal
      phalangeal bone and the third metacarpal bone (Mc3) and the Mc3 proximal
      metaphysis. Nineteen 2- and 3-year old horses in training were exposed either to
      spontaneous exercise at pasture (PASTEX group) or additional imposed exercise
      (CONDEX group) from a very young age. Quantitative computed tomography scans were
      analysed for bone mineral content, size, bone mineral density, periosteal and
      endosteal circumference, cortical thickness and an estimate of bone strength. The
      bones of the CONDEX horses were bigger and stronger than those of the PASTEX
      horses at the start of the observation period, and these differences were
      maintained after adjusting for training workload. Increase in the bone strength
      index was through size and not density increase. Density increased during
      training and decreased during paddock rest between the two training campaigns,
      during which time bone strength continued to increase because of the slow growth
      that was still occurring. The greatest variance in the response to the training
      exercise of diaphyseal bone mineral content, bone strength index or cortical
      thickness was associated with the cumulative workload index at the gallop,
      although statistically significant unexplained variances remained. There were no
      differences in bone response to training, with the exception of the endosteal
      circumference at 55% of the Mc3 length from the carpometacarpal joint space
      between CONDEX and PASTEX, which indicated that young horses may be able to be
      exercised slightly more vigorously than currently accepted.

PMID- 21855375
TI  - The incidence of traumatic brain injury in young people in the catchment area of
      the University Hospital Rotterdam, The Netherlands.
AB  - BACKGROUND: Traumatic brain injury (TBI) is in the developed countries the most
      common cause of death and disability in childhood. AIM: The purpose of this study
      is to estimate the incidence of TBI for children and young people in an urbanised
      region of the Netherlands and to describe relevant characteristics of this group.
      METHODS: Patients, aged 1 month - 24 years who presented with traumatic brain
      injury at the Erasmus University Hospital (including the Sophia Children's
      Hospital) in 2007 and 2008 were included in a retrospective study. Data were
      collected by means of diagnosis codes and search terms for TBI in patient
      records. The incidence of TBI in the different referral areas of the hospital for
      standard, specialised and intensive patient care was estimated. RESULTS: 472
      patients met the inclusion criteria. The severity of the Injury was classified as
      mild in 342 patients, moderate in 50 patients and severe in 80 patients. The
      total incidence of traumatic brain injury in the referral area of the Erasmus
      University Hospital was estimated at 113.9 young people per 100.000. The
      incidence for mild traumatic brain injury was estimated at 104.4 young people,
      for moderate 6.1 and for severe 3.4 young people per 100.000. CONCLUSION: The
      ratio for mild, moderate and severe traumatic brain injury in children and young
      people was 33.7-1.8-1.In the mild TBI group almost 17% of the patients reported
      sequelae. The finding that 42% of them had a normal brain CT scan at admission
      underwrites the necessity of careful follow up of children and young people with
      mild TBI.

PMID- 21855380
TI  - Malignant glandular lesions and glandular differentiation in invasive/noninvasive
      urothelial carcinoma of the urinary bladder.
AB  - Although the lumen of the urinary bladder is covered with only urothelial
      epithelium, malign glandular lesions (eg, nonurachal adenocarcinoma) and benign
      lesions (eg, cystitis cystica and cystitis glandularis) can also rarely occur in
      this site due to its characteristic embryologic development. Glandular
      differentiation is uncommon in urothelial carcinomas and is even less common in
      noninvasive urothelial cancers. In addition, in situ urothelial carcinomas are
      more likely to progress in the presence of glandular differentiation toward high
      grade urothelial carcinomas and/or aggressive urothelial carcinomas. Pure
      nonurachal adenocarcinomas and mixed carcinomas (urothelial carcinoma and
      adenocarcinoma) are very rare, and their pathogenesis is not clear. Most of the
      nonurachal adenocarcinomas are thought to arise on the grounds of cystitis
      glandularus with intestinal metaplasia. Here, I present 2 cases with noninvasive
      urothelial carcinoma with substantial glandular differentiation showing
      progression to signet ring cell carcinoma and invasive urothelial carcinoma, one
      case with mixed carcinoma (urothelial carcinoma and adenocarcinoma) and another
      case with pure adenocarcinoma developing from cystitis glandularis with
      intestinal metaplasia, and discuss malign glandular lesions in the bladder and
      invasive/noninvasive urothelial carcinomas with glandular differentiation.

PMID- 21855381
TI  - The immunohistochemical profile of atypical eosinophilic syncytial changes vs
      serous carcinoma.
AB  - Endometrial epithelial cytoplasmic change (EECC) is an adaptive cytoplasmic
      change commonly seen in the endometrium. Previously considered "metaplasia," EECC
      is now the preferred term because it offers a descriptive designation without
      implying a specific mechanism of development. There are 5 types of EECC:
      squamous, ciliated cell, eosinophilic, mucinous, and secretory (clear cell and
      hobmail cell) changes. Eosinophilic syncytial change (ESC) is a similar but
      unrelated degenerative change seen in endometrial breakdown. Some cases of ESC
      show atypical cytologic features that may resemble endometrial adenocarcinoma.
      Thirteen endometrial biopsy and curettage specimens with atypical ESCs (AESCs)
      were compared against 10 hysterectomy specimens with endometrial serous
      carcinoma. Clinical information and immunohistochemical staining profiles for
      markers phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53,
      and Ki-67 were evaluated in each case. All 13 cases of AESC (100%) showed
      moderate-to-strong staining for PTEN, whereas PTEN expression was absent in all
      endometrial serous carcinomas (P < .001). Seven cases of AESC (54%) showed focal,
      weak positivity for p53, whereas all cases of serous carcinoma (100%) showed
      strong staining (P < .001). The Ki-67 index was low (3%-15%) and found in only 3
      cases in AESC (32%) but was high (60%-90%) in all cases of endometrial serous
      carcinoma (100%) (P < .001). Atypical ESC and serous carcinoma share several
      morphological features on hematoxylin and eosin-stained sections that may
      complicate accurate diagnosis. The PTEN, p53, and Ki-67 staining profile can
      effectively distinguish between AESC and malignancy in difficult cases, providing
      an invaluable tool for a challenging diagnostic dilemma.

PMID- 21855384
TI  - [Intensity-modulated radiation therapy for anal carcinoma].
AB  - Anal canal carcinoma are highly curable by irradiation, combined with
      chemotherapy in locally advanced disease, with preservation of sphincter
      function. The clinical target volume for the nodes is extended, often including
      the inguinal nodes, which is not usual for other pelvic tumours. Acute and late
      effects are correlated with the volume and dose delivered to organs at risk, i.
      e. small bowel, bladder and increased by concomitant chemotherapy. Intensity
      modulated irradiation (IMRT) makes it possible to optimize the dose distribution
      in this "complex U shaped" volume, while maintaining the dose distribution for
      the target volumes. The conversion from conformal irradiation to IMRT
      necessitates good knowledge of the definition and skills to delineate target
      volumes and organs at risk, including new volumes needed to optimize the dose
      distribution. Dosimetric and clinical benefits of IMRT are described, based on
      early descriptions and evidence-based publication. The growing development of
      IMRT in anal canal radiotherapy must be encouraged, and long-term benefits should
      be soon published. Radiation oncologists should precisely learn IMRT
      recommendations before starting the technique, and evaluate its early and late
      results for adverse effects, but also for long-term tumour control.

PMID- 21855383
TI  - Seroprevalence of antibodies to influenza A/H1N1/2009 among transmission risk
      groups after the second wave in Mexico, by a virus-free ELISA method.
AB  - OBJECTIVE: No serological studies have been performed in Mexico to assess the
      seroprevalence of influenza A/H1N1/2009 in groups of people according to the
      potential risk of transmission. The aim of this study was to determine the
      seroprevalence of antibodies against influenza A/H1N1/2009 in subjects in Mexico
      grouped by risk of transmission. METHODS: Two thousand two hundred and twenty-two
      subjects were categorized into one of five occupation groups according to the
      potential risk of transmission: (1) students, (2) teachers, (3) healthcare
      workers, (4) institutional home residents aged >60 years, and (5) general
      population. Seroprevalence by potential transmission group and by age grouped
      into decades was determined by a virus-free ELISA method based on the recombinant
      receptor-binding domain of the hemagglutinin of influenza A/H1N1/2009 virus as
      antigen (85% sensitivity; 95% specificity). The Wilson score, Chi-square test,
      and logistic regression models were used for the statistical analyses. RESULTS:
      Seroprevalence for students was 47.3%, for teachers was 33.9%, for older adults
      was 36.5%, and for the general population was 33.0%, however it was only 24.6%
      for healthcare workers (p=0.011). Of the students, 56.6% of those at middle
      school, 56.4% of those at high school, 52.7% of those at elementary school, and
      31.1% of college students showed positive antibodies (p<0.001). Seroprevalence
      was 44.6% for college teachers, 31.6% for middle school teachers, and 29.8% for
      elementary school teachers, but was only 20.3% for high school teachers
      (p=0.002). CONCLUSIONS: The student group was the group most affected by
      influenza A/H1N1/2009, while the healthcare worker group showed the lowest
      prevalence. Students represent a key target for preventive measures.

PMID- 21855385
TI  - [First epidemiologic data about phloroglucinol exposure during first trimester of
      pregnancy].
AB  - OBJECTIVE: Phloroglucinol is used to prevent gastric, intestine or urogenital
      spasms. In France, many pregnant women are exposed to phloroglucinol for which no
      data are available about its use in pregnancy. The present study, using EFEMERIS
      database, investigates potential teratogenic risk of phloroglucinol in pregnancy.
      MATERIALS AND METHODS: EFEMERIS is a database including prescribed and delivered
      drugs during pregnancy (data from Caisse Primaire d'Assurance Maladie of Haute
      Garonne) and outcomes (data from Maternal and Infant Protection Service and from
      Antenatal diagnostic Centre). Women delivered from July 1st 2004 to June 30th
      2008 in Haute-Garonne and registered in the French Health Insurance Service were
      included into EFEMERIS database. We compared pregnancy outcomes and newborn
      health between women exposed to phloroglucinol during organogenesis and non
      exposed women. Malformations were classified according to Eurocat classification.
      RESULTS: Five thousand one hundred and thirty-two newborns (12.7%) exposed during
      organogenesis to phloroglucinol were compared to 35,223 controls (non exposed
      newborns). The mean number of different drugs prescribed during the first
      trimester of pregnancy per woman was higher in women exposed to phloroglucinol
      than in non-exposed women (6.4 +/- 4.3 versus 2.4 +/- 3.3, P < 10(-4)). Among
      newborns, 126 (2.5%) had a malformation versus 804 (2.3%) in control newborns
      (OR=1.1, [0.9-1.3]). The present study was powered to find a 1.3 fold increase in
      the overall rate of major anomalies. DISCUSSION AND CONCLUSION: This first
      epidemiologic study about phloroglucinol in pregnancy does not support evidence
      of a teratogenic risk for phloroglucinol in humans.

PMID- 21855382
TI  - Deficient degradation of homotrimeric type I collagen, alpha1(I)3 glomerulopathy
      in oim mice.
AB  - Col1a2-deficient (oim) mice synthesize homotrimeric type I collagen due to
      nonfunctional proalpha2(I) collagen chains. Our previous studies revealed a
      postnatal, progressive type I collagen glomerulopathy in this mouse model, but
      the mechanism of the sclerotic collagen accumulation within the renal mesangium
      remains unclear. The recent demonstration of the resistance of homotrimeric type
      I collagen to cleavage by matrix metalloproteinases (MMPs), led us to investigate
      the role of MMP-resistance in the glomerulosclerosis of Col1a2-deficient mice. We
      measured the pre- and post-translational expression of type I collagen and MMPs
      in glomeruli from heterozygous and homozygous animals. Both the heterotrimeric
      and homotrimeric isotypes of type I collagen were equally present in whole
      kidneys of heterozygous mice by immunohistochemistry and biochemical analysis,
      but the sclerotic glomerular collagen was at least 95-98% homotrimeric,
      suggesting homotrimeric type I collagen is the pathogenic isotype of type I
      collagen in glomerular disease. Although steady-state MMP and Col1a1 mRNA levels
      increased with the disease progression, we found these changes to be a secondary
      response to the deficient clearance of MMP-resistant homotrimers. Increased renal
      MMP expression was not sufficient to prevent homotrimeric type I collagen
      accumulation.

PMID- 21855386
TI  - [Accreditation according to the ISO/EN 15,189 referential: compulsory for
      assisted conception unit. Main points for the clinician].

PMID- 21855387
TI  - [Interest of robot-assisted laparoscopy in the initial surgical training:
      Resident survey].
AB  - OBJECTIVE: This survey evaluated if residents felt a benefit to their
      participation in robot-assisted procedures and highlights the interest of robot
      in the initial surgical training. PATIENTS AND METHODS: A questionnaire was
      submitted to 33 residents participating as assistants in robot-assisted surgical
      procedures in our department and to seven residents of the Chapel Hill hospital,
      North Carolina, USA. Items rated their experience with the robot, their feeling
      during the surgical procedures and whether they thought they improved their
      technical skills. RESULTS: The majority of French residents felt passive during
      the procedures (97%) or bored (75%); most of them found an immediate interest to
      learn anatomy (72.7%) and surgical procedures (66.7%). Then, a minority of them
      reported an improvement of their knowledge in anatomy (39.4%), in surgical
      procedures (24.2%), and conventional laparoscopy (9.1%). Most of French residents
      are not willing to repeat the experience as an assistant (81.8%), whereas they
      showed great interest in practicing robot-assisted surgery later. The oldest
      residents benefited more than younger in learning anatomy and surgical
      procedures. US resident' ratings concerning the contribution of the robot in
      their training were generally more positive. They were all convinced they made
      progress in anatomy, as in surgical techniques and they all wanted to repeat such
      procedures. DISCUSSION AND CONCLUSION: This work demonstrates the pedagogical
      value of using the robot for teaching surgical procedures and anatomy. It also
      suggests the establishment of training programs dedicated to the learning of
      robot-assisted surgery in gynaecology, in parallel with training in conventional
      laparoscopy.

PMID- 21855388
TI  - Ultrasound-promoted intramolecular direct arylation in a capillary flow
      microreactor.
AB  - An intramolecular direct arylation of various aryl bromides was performed using
      ultrasonic irradiation and a continuous flow capillary microreactor. The present
      procedure provided a higher functional group tolerance, ligand-free, milder
      reaction conditions and a shorter reaction time for the direct arylation compared
      with the conventional methods. The ultrasonic irritation not only greatly
      promoted the conversion and selectivity of the direct arylation, but also solved
      the clogging problem of the microreactor for solid-forming reaction and made the
      reaction run smoothly.

PMID- 21855389
TI  - A facile and efficient ultrasound-assisted synthesis of novel dispiroheterocycles
      through 1,3-dipolar cycloaddition reactions.
AB  - A facile and efficient one-pot three-component procedure for synthesis of novel
      dispirooxindolecyclo[pyrrolo[1,2-c]thiazole-6,5'-thiazolidine] derivatives
      without any catalysts under ultrasonic condition has been developed. Combining
      with the advantages of sonochemistry, such as mild reaction conditions, good
      yield and short reaction times, we have made a progress on construction of novel
      disiproheterocyclic compounds via the 1,3-dipolar cycloaddition of azomethine
      ylides. Several experiments were especially carried out for investigating the
      acceleration mechanism of ultrasound on the cycloaddition.

PMID- 21855390
TI  - Comparison of Ho:YAG laser and coblation for interface tissue removal in
      minimally invasive hip refixation procedures.
AB  - Aseptic loosening is the major failure mode for hip prostheses. Currently,
      loosened prostheses are revised during open surgery. Because of a high
      complication rate, this demanding procedure cannot be performed in patients with
      a poor general health. We are developing an alternative minimally invasive
      refixation procedure that leaves the prostheses in place, but relies on removing
      the interface membrane and replacing it with bone cement. The aim of this study
      was to evaluate two interface tissue removal techniques - Ho:YAG laser and
      coblation - based on two criteria: thermal damage and the ablation rate. In vitro
      a loosened hip prosthesis was simulated by implanting a prosthesis in each of 10
      cadaver femora. Artificially created peri-prosthetic lesions were filled with
      chicken liver as an interface tissue substitute. We measured temperatures in
      vitro at different radial distances from the site of removal. Temperatures during
      removal were recorded both inside the interface tissue and in the surrounding
      bone. This study demonstrated that temperatures generated in the bone do not
      result in thermal damage (increasing less than 10 degrees C relative to body
      temperature). Temperatures inside the interface tissue are sufficiently high to
      destroy the interface tissue (T>50 degrees C, duration>1 min). Using laser
      instead of coblation for the removal of interface tissue resulted in higher
      temperatures - thus a faster removal of interface tissue. This is in accordance
      with the ablation rate test. Ho:YAG laser is advantageous compared to coblation.
      We consider Ho:YAG laser a promising tool for interface tissue removal.

PMID- 21855391
TI  - A new methodology for intra-breath control of mechanical ventilation.
AB  - Recent improvements in digital control strategies are driving the implementation
      of innovative pulmonary ventilation modalities able to support the physician in
      the intensive care through a better management of the patient's respiratory
      pathologies. New control strategies, such as intra-breath ones, which guarantee
      successful patient-machine synchronization and dynamic adjustment to the patient,
      still require improvements in the control of the breathing process. Such
      improvements can be achieved by decreasing the response time of the actuation
      system driving the mechanical ventilators. This paper presents a new methodology
      of intra-breath control to generate traditional and high frequency ventilation
      techniques. The methodology is implemented through a custom-developed electro
      mechanical system, which consists of on/off solenoid valves driven by a fast
      switching driver circuit. In vitro experimental trials show the system's ability
      to generate almost continuous flow-rate patterns in different shapes, a time
      resolution down to 20 ms, flow-rate resolution of 1L/min, and repeatability of
      0.5L/min. Experimental results show that the proposed electro-mechanical system
      can be used as a stand-alone hardware solution for both intra-breath control
      techniques and high frequency ventilation.

PMID- 21855392
TI  - Quantification of the accuracy of MRI generated 3D models of long bones compared
      to CT generated 3D models.
AB  - Orthopaedic fracture fixation implants are increasingly being designed using
      accurate 3D models of long bones based on computer tomography (CT). Unlike CT,
      magnetic resonance imaging (MRI) does not involve ionising radiation and is
      therefore a desirable alternative to CT. This study aims to quantify the accuracy
      of MRI-based 3D models compared to CT-based 3D models of long bones. The femora
      of five intact cadaver ovine limbs were scanned using a 1.5 T MRI and a CT
      scanner. Image segmentation of CT and MRI data was performed using a multi
      threshold segmentation method. Reference models were generated by digitising the
      bone surfaces free of soft tissue with a mechanical contact scanner. The MRI- and
      CT-derived models were validated against the reference models. The results
      demonstrated that the CT-based models contained an average error of 0.15 mm while
      the MRI-based models contained an average error of 0.23 mm. Statistical
      validation shows that there are no significant differences between 3D models
      based on CT and MRI data. These results indicate that the geometric accuracy of
      MRI based 3D models was comparable to that of CT-based models and therefore MRI
      is a potential alternative to CT for generation of 3D models with high geometric
      accuracy.

PMID- 21855393
TI  - An investigation of co-speech gesture production during action description in
      Parkinson's disease.
AB  - INTRODUCTION: Parkinson's disease (PD) can impact enormously on speech
      communication. One aspect of non-verbal behaviour closely tied to speech is co
      speech gesture production. In healthy people, co-speech gestures can add
      significant meaning and emphasis to speech. There is, however, little research
      into how this important channel of communication is affected in PD. METHODS: The
      present study provides a systematic analysis of co-speech gestures which
      spontaneously accompany the description of actions in a group of PD patients (N =
      23, Hoehn and Yahr Stage III or less) and age-matched healthy controls (N = 22).
      The analysis considers different co-speech gesture types, using established
      classification schemes from the field of gesture research. The analysis focuses
      on the rate of these gestures as well as on their qualitative nature. In doing
      so, the analysis attempts to overcome several methodological shortcomings of
      research in this area. RESULTS: Contrary to expectation, gesture rate was not
      significantly affected in our patient group, with relatively mild PD. This
      indicates that co-speech gestures could compensate for speech problems. However,
      while gesture rate seems unaffected, the qualitative precision of gestures
      representing actions was significantly reduced. CONCLUSIONS: This study
      demonstrates the feasibility of carrying out fine-grained, detailed analyses of
      gestures in PD and offers insights into an as yet neglected facet of
      communication in patients with PD. Based on the present findings, an important
      next step is the closer investigation of the qualitative changes in gesture
      (including different communicative situations) and an analysis of the
      heterogeneity in co-speech gesture production in PD.

PMID- 21855394
TI  - Genetics of autism spectrum disorders.
AB  - Characterized by a combination of abnormalities in language, social cognition and
      mental flexibility, autism is not a single disorder but a neurodevelopmental
      syndrome commonly referred to as autism spectrum disorder (ASD). Several dozen
      ASD susceptibility genes have been identified in the past decade, collectively
      accounting for 10-20% of ASD cases. These findings, although demonstrating that
      ASD is etiologically heterogeneous, provide important clues about its
      pathophysiology. Diverse genetic and genomic approaches provide evidence
      converging on disruption of key biological pathways, many of which are also
      implicated in other allied neurodevelopmental disorders. Knowing the genes
      involved in ASD provides us with a crucial tool to probe both the specificity of
      ASD and the shared neurobiological and cognitive features across what are
      considered clinically distinct disorders, with the goal of linking gene to brain
      circuits to cognitive function.

PMID- 21855395
TI  - Bacterial replicases and related polymerases.
AB  - Bacterial replicases are complex, tripartite replicative machines. They contain a
      polymerase, Pol III, a beta(2) processivity factor and a DnaX complex ATPase that
      loads beta(2) onto DNA and chaperones Pol III onto the newly loaded beta(2). Many
      bacteria encode both a full length tau and a shorter gamma form of DnaX by a
      variety of mechanisms. The polymerase catalytic subunit of Pol III, alpha,
      contains a PHP domain that not only binds to prototypical E Mg(2+)-dependent
      exonuclease, but also contains a second Zn(2+)-dependent proofreading
      exonuclease, at least in some bacteria. Replication of the chromosomes of low GC
      Gram-positive bacteria require two Pol IIIs, one of which, DnaE, appears to
      extend RNA primers a only short distance before handing the product off to the
      major replicase, PolC. Other bacteria encode a second Pol III (ImuC) that
      apparently replaces Pol V, required for induced mutagenesis in E. coli.
      Approaches that permit simultaneous biochemical screening of all components of
      complex bacterial replicases promise inhibitors of specific protein targets and
      reaction stages.

PMID- 21855396
TI  - Attraction of tip-growing pollen tubes by the female gametophyte.
AB  - Pollen tube guidance is the mechanism whereby the direction of pollen tube growth
      is controlled by female cells of the pistil. Some key genes and molecules have
      recently been identified as being involved in pollen tube guidance. In this
      review article, we discuss the molecular basis of pollen tube guidance,
      especially in Arabidopsis thaliana, by summarizing recent progress in various
      plant species. Attractant molecules and receptors for gametophytic pollen tube
      guidance are the focus of this article.

PMID- 21855397
TI  - Apyrases, extracellular ATP and the regulation of growth.
AB  - Although no definitive receptor for extracellular ATP (eATP) has been identified
      in plants, there is now stronger physiological evidence that the effects of eATP
      on plant growth are mediated by a receptor, or, as in animals, by multiple
      receptors. Recent papers clarify how extracellular nucleotides induce changes in
      [Ca(2+)](cyt), and the production of nitric oxide (NO) and reactive oxygen
      species. They document links between eATP signaling and the synthesis or
      transport of hormones, and they reveal that applied nucleotides can regulate the
      aperture of stomates, which release ATP when stimulated by light and hormones.
      Ectoapyrases (ecto-nucleoside triphosphate-diphosphohydrolase) help control both
      the diverse signaling changes and downstream growth changes induced by
      extracellular nucleotides by limiting their concentration in the extracellular
      matrix (ECM).

PMID- 21855398
TI  - She's the boss: signaling in pollen tube reception.
AB  - In angiosperms, the sperm cells are carried within the pollen tubes (male
      gametophytes) to the female gametophyte so that double fertilization can occur.
      The female gametophyte exerts control over the male, with specialized cells known
      as synergids guiding the pollen tubes and controlling their behavior when they
      enter the female gametophyte so that the sperm cells can be delivered to the egg
      and central cell. Upon pollen tube arrival at the ovule, signal transduction
      cascades mediated by receptor-like kinases are initiated in both the synergid and
      the tip of the pollen tube, leading to synergid cell death and pollen tube
      rupture. In this review, we discuss the role of these receptors and of newly
      discovered members of the pollen tube reception pathway.

PMID- 21855399
TI  - Synthesis, spectroscopic, antimicrobial, DNA binding and cleavage studies of some
      metal complexes involving symmetrical bidentate N, N donor Schiff base ligand.
AB  - The Schiff base ligand, N,N'-bis-(4-isopropylbenzaldimine)-1,2-diaminoethane (L),
      obtained by the condensation of 4-isopropylbenzaldehyde and 1,2-diaminoethane,
      has been used to synthesize the complexes of the type [ML(2)X(2)] [M = Co(II),
      Ni(II) and Zn(II); X = Cl and OAc]. The newly synthesized ligand (L) and its
      complexes have been characterized on the basis of elemental analyses, mass, (1)H
      and (13)C-NMR, molar conductance, IR, UV-vis, magnetic moment, CV and thermal
      analyses, powder XRD and SEM. IR spectral data show that the ligand is
      coordinated to the metal ions in a bidentate manner. The geometrical structures
      of these complexes are found to be octahedral. Interestingly, reaction with
      Cu(II) ion with this ligand undergoes hydrolytic cleavage to form ethylenediamine
      copper(II) complex and the corresponding aldehyde. The antimicrobial results
      indicate that the chloro complexes exhibit more activity than the acetato
      complexes. The complexes bind to CT-DNA by intercalation modes. Novel chloroform
      soluble ZnL(2)Cl(2) complex exhibits tremendous antimicrobial, DNA binding and
      cleaving properties.

PMID- 21855400
TI  - Highly selective fluorescent recognition of Zn2+ based on naphthalene macrocyclic
      derivative.
AB  - A new macrocyclic chemosensor containing two naphthalene fluorophores has been
      synthesized. The fluorescent properties of this receptor has been studied in the
      presence of various metal ions such as Na(+), Ag(+), Cr(3+), Mn(2+), Fe(3+),
      Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+) and Pb(2+). When increasing concentrations
      of Zn(2+) ions were introduced, the emission of L was drastically increased (EFE
      = 4.34). This special change was not observed when other metal ions were used;
      such highly selective fluorescent response indicates that this receptor can
      easily discriminate Zn(2+) ions from other similar species. Model calculations at
      DFT level further suggest the possible interaction mode, and relatively steric
      position between the host and guest also influence the optical response.

PMID- 21855401
TI  - Spectral-optical-electrical-thermal properties of deposited thin films of nano
      sized calcium(II)-8-hydroxy-5,7-dinitroquinolate complex.
AB  - Spectral-optical-electrical-thermal properties of deposited thin films of nano
      sized calcium(II)-8-hydroxy-5,7-dinitroquinolate complex, Ca[((NO(2))(2)
      8HQ)(2)], were explored, studied and evaluated in this work. Thin films of
      Ca[((NO(2))(2)-8HQ)(2)] were assembled by using a direct, simple and efficient
      layer-by-layer (LBL) chemical deposition technique. The optical properties of
      thin films were investigated by using spectrophotometric measurements of
      transmittance and reflectance at normal incidence in the wavelength range 200
      2500 nm. The refractive index, n, and the absorption index, k, of Ca[((NO(2))(2)
      8HQ)(2)] films were determined from the measured transmittance and reflectance.
      The real and imaginary dielectric constants were also determined. The analysis of
      the spectral behavior of the absorption coefficient in the intrinsic absorption
      region reveals a direct allowed transition with band gaps of 1.1 eV and 2.4 eV
      for the optical and transport energy gaps, respectively. The current-voltage
      characteristics of Ca[((NO(2))(2)-8HQ)(2)] showed a trap-charge limited
      conduction in determining the current at the intermediate and high bias regimes.
      Graphical representation of the current-voltage characteristics yields three
      distinct linear parts indicating the existence of three conduction mechanisms.
      Structural characterization and identification were confirmed by using Fourier
      transform infrared spectroscopy (FT-IR). Scanning electron microscopy (SEM) was
      also used to image the surface morphology of the deposited nano-sized metal
      complex and such study revealed a high homogeneity in surface spherical particle
      distribution with average particles size in the range 20-40 nm. Thermal
      gravimetric analysis (TGA) was also studied for [(NO(2))(2)-8HQ] and
      Ca[((NO(2))(2)-8HQ)(2)] to evaluate and confirm the thermal stability
      characteristics incorporated into the synthesized nano-sized Ca[((NO(2))(2)
      8HQ)(2)] complex.

PMID- 21855402
TI  - Ligational behaviour of lomefloxacin drug towards Cr(III), Mn(II), Fe(III),
      Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and UO(2)(VI) ions: synthesis, structural
      characterization and biological activity studies.
AB  - Nine new mononuclear Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II),
      Th(IV) and UO(2)(VI) complexes of lomefloxacin drug were synthesized. The
      structures of these complexes were elucidated by elemental analyses, IR, XRD, UV
      vis, (1)H NMR as well as conductivity and magnetic susceptibility measurements
      and thermal analyses. The dissociation constants of lomefloxacin and stability
      constants of its binary complexes have been determined spectrophotometrically in
      aqueous solution at 25+/-1 degrees C and at 0.1 M KNO(3) ionic strength. The
      discussion of the outcome data of the prepared complexes indicate that the
      lomefloxacin ligand behaves as a neutral bidentate ligand through OO coordination
      sites and coordinated to the metal ions via the carbonyl oxygen and protonated
      carboxylic oxygen with 1:1 (metal:ligand) stoichiometry for all complexes. The
      molar conductance measurements proved that the complexes are electrolytes. The
      powder XRD study reflects the crystalline nature for the investigated ligand and
      its complexes except Mn(II), Zn(II) and UO(2)(II). The geometrical structures of
      these complexes are found to be octahedral. The thermal behaviour of these
      chelates is studied where the hydrated complexes lose water molecules of
      hydration in the first steps followed by decomposition of the anions, coordinated
      water and ligand molecules in the subsequent steps. The activation thermodynamic
      parameters are calculated using Coats-Redfern and Horowitz-Metzger methods. A
      comparative study of the inhibition zones of the ligand and its metal complexes
      indicates that metal complexes exhibit higher antibacterial effect against one or
      more bacterial species than the free LFX ligand. The antifungal and anticancer
      activities were also tested. The antifungal effect of almost metal complexes is
      higher than the free ligand. LFX, [Co(LFX)(H(2)O)(4)].Cl(2) and
      [Zn(LFX)(H(2)O)(4)].Cl(2) were found to be very active with IC50 values 14, 11.2
      and 43.1, respectively. While, other complexes had been found to be inactive at
      lower concentration than 100 MUg/ml.

PMID- 21855403
TI  - Selective and sensitive optical chemosensor for detection of Ag(I) ions based on
      2(4-hydroxy pent-3-en-2-ylideneamine) phenol in aqueous samples.
AB  - A selective and sensitive chemosensor, based on the 2(4-hydroxy pent-3-en-2
      ylideneamine) phenol (HPYAP) as chromophore, has been developed for colorimetric
      and visual detection of Ag(I) ions. HPYAP shows a considerable chromogenic
      behavior toward Ag(I) ions by changing the color of the solution from pale-yellow
      to very chromatic-yellow, which can be easily detected with the naked-eye. The
      chemosensor exhibited selective absorbance enhancement to Ag(I) ions in water
      samples over other metal ions at 438 nm, with a linear range of 0.4-500 MUM
      (r(2)=0.999) and a limit of detection 0.07 MUM of Ag(I) ions with UV-vis
      spectrophotometer detection. The relative standard deviation (RSD) for 100 MUM
      Ag(I) ions was 2.05% (n=7). The proposed method was applied for the determination
      Ag(I) ions in water and waste water samples.

PMID- 21855404
TI  - Effect of NaCl and KCl doping on the growth of sulphamic acid crystals.
AB  - The nonlinear optical single crystals of doped sulphamic acid (SA) were grown
      from aqueous solution by doping with NaCl and KCl using slow evaporation method.
      Powder X-ray diffraction studies confirm that the grown crystals belong to
      orthorhombic system. The density and melting point measurements of the grown
      crystals were determined by floatation technique and capillary tube method,
      respectively. The range of optical transmittance was ascertained by recording the
      UV-Vis-NIR spectrum. Atomic absorption study reveals the presence of dopants in
      the doped crystals. The thermal analyses indicated that the doped SA crystals are
      more stable than pure crystals. The Vicker's microhardness studies revealed that
      the dopants increased the hardness of the crystals. SHG efficiency studies of the
      crystals are found to be increased in the presence of NaCl and KCl dopants.

PMID- 21855405
TI  - Non-invasive sample collection for respiratory virus testing by multiplex PCR.
AB  - BACKGROUND: Identifying respiratory pathogens within populations is difficult
      because invasive sample collection, such as with nasopharyngeal aspirate (NPA),
      is generally required. PCR technology could allow for non-invasive sampling
      methods. OBJECTIVE: Evaluate the utility of non-invasive sample collection using
      anterior nare swabs and facial tissues for respiratory virus detection by
      multiplex PCR. STUDY DESIGN: Children aged 1 month-17 years evaluated in a
      pediatric emergency department for respiratory symptoms had a swab, facial
      tissue, and NPA sample collected. All samples were tested for respiratory viruses
      by multiplex PCR. Viral detection rates were calculated for each collection
      method. Sensitivity and specificity of swabs and facial tissues were calculated
      using NPA as the gold standard. RESULTS: 285 samples from 95 children were
      evaluated (92 swab-NPA pairs, 91 facial tissue-NPA pairs). 91% of NPA, 82% of
      swab, and 77% of tissue samples were positive for >=1 virus. Respiratory
      syncytial virus (RSV) and human rhinovirus (HRV) were most common. Overall, swabs
      were positive for 74% of virus infections, and facial tissues were positive for
      58%. Sensitivity ranged from 17 to 94% for swabs and 33 to 84% for tissues.
      Sensitivity was highest for RSV (94% swabs and 84% tissues). Specificity was
      >=95% for all viruses except HRV for both collection methods. CONCLUSIONS:
      Sensitivity of anterior nare swabs and facial tissues in the detection of
      respiratory viruses by multiplex PCR varied by virus type. Given its simplicity
      and specificity, non-invasive sampling for PCR testing may be useful for
      conducting epidemiologic or surveillance studies in settings where invasive
      testing is impractical or not feasible.

PMID- 21855406
TI  - Purple pigments: the pathophysiology of acute porphyric neuropathy.
AB  - The porphyrias are inherited metabolic disorders arising from disturbance in the
      haem biosynthesis pathway. The neuropathy associated with acute intermittent
      porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen
      deaminase (PBGD) and is characterised by motor-predominant features. Definitive
      diagnosis often encompasses a combination of biochemical, enzyme analysis and
      genetic testing, with clinical neurophysiological findings of a predominantly
      motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays
      during an acute attack. If administered early, intravenous haemin may prevent
      progression of neuropathy. While the pathophysiology of AIP neuropathy remains
      unclear, axonal dysfunction appears intrinsically linked to the effects of neural
      energy deficits acquired through haem deficiency coupled to the neurotoxic
      effects of porphyrin precursors. The present review will provide an overview of
      AIP neuropathy, including discussion of recent advances in understanding
      developed through neurophysiological approaches that have further delineated the
      pathophysiology of axonal degeneration.

PMID- 21855408
TI  - Effectiveness of evening phototherapy for insomnia is reduced by bright daytime
      light exposure.
AB  - OBJECTIVE: To examine the effect of ambulatory daytime light exposure on phase
      delays and on the advances produced by timed exposure to bright evening or
      morning light. METHODS: As a subset of a larger study, 32 older (63.0 +/- 6.43
      years) adults with primary insomnia were randomized to an at-home, single-blind,
      12-week, parallel-group study entailing daily exposure to 45 min of scheduled
      evening or morning bright (~4000 lux) light. Light exposure patterns during the
      baseline and the last week of treatment were monitored using actigraphs with
      built-in illuminance detectors. Circadian phase was determined through analysis
      of in-laboratory collected plasma melatonin. RESULTS: Less daytime light exposure
      during the last week of treatment was significantly associated with larger phase
      delays in response to evening light (r's>0.78). Less daytime light exposure
      during the last week of treatment was also associated with a significant delay in
      wake time (r's>-0.75). There were no such relationships between light exposure
      history and phase advances in response to morning light. CONCLUSIONS: Greater
      light exposure during the daytime may decrease the ability of evening light, but
      not morning light, exposure to engender meaningful changes of circadian phase.

PMID- 21855409
TI  - Real-time multiplex PCR for simultaneous detection of Campylobacter jejuni,
      Salmonella, Shigella and Yersinia species in fecal samples.
AB  - Diarrheal diseases due to notifiable bacterial infections require rapid diagnosis
      of the causative pathogens. To facilitate detection, a real-time multiplex PCR
      was developed that identifies common diarrhea-causing bacteria in fecal samples.
      On the basis of published sequence data, sets of primers and probes were designed
      that were specific for Campylobacter jejuni, Salmonella, Shigella/enteroinvasive
      Escherichia coli EIEC, and Yersinia species, suitable for use in a one-tube PCR
      assay. The assay was assessed using a list of 137 well-defined intestinal
      bacterial strains or isolates. Furthermore, 393 routine clinical stool samples
      were analyzed, and the results of real-time multiplex PCR were compared with
      those obtained by established microbiological methods. The PCR yielded results
      within 3h including DNA purification. No false-positive signals or cross
      reactions were observed. The analytical sensitivity was 10(3)cfumL(-1) for
      Campylobacter jejuni, 10(4)cfumL(-1) for Salmonella, and 10(5)cfumL(-1) for
      Shigella/EIEC and Yersinia, respectively. Compared with culture, PCR detected 79
      out of 81 Campylobacter jejuni (97.5%), 71 out of 74 Salmonella (96%), 8 out of 8
      Shigella (100%), and 10 out of 10 Yersinia-positive (100%) clinical samples. In
      culture-negative samples (n=192), PCR additionally detected 2 Shigella, 1
      Salmonella, and 5 Campylobacter jejuni infections. Thus, the new real-time
      multiplex PCR provides reliable results within a short time and might be useful
      as an additional diagnostic tool whenever time is important in the diagnosis of
      enteropathogenic bacteria.

PMID- 21855410
TI  - Hyperinflation of lungs during redo-sternotomy, a safer technique.
AB  - Increasing numbers of patients are being referred for repeat cardiac procedures
      and redo-sternotomy is technically more arduous as well as time consuming. We
      describe our unique technique to overcome this challenging task by hyperinflating
      the lungs as a useful manoeuvre.

PMID- 21855407
TI  - Sex differences in auditory subcortical function.
AB  - OBJECTIVE: Sex differences have been demonstrated in the peripheral auditory
      system as well as in higher-level cognitive processing. Here, we aimed to
      determine if the subcortical response to a complex auditory stimulus is encoded
      differently between the sexes. METHODS: Using electrophysiological techniques, we
      assessed the auditory brainstem response to a synthesized stop-consonant speech
      syllable [da] in 76 native-English speaking, young adults (38 female). Timing and
      frequency components of the response were compared between males and females to
      determine which aspects of the response are affected by sex. RESULTS: A
      dissimilarity between males and females was seen in the neural response to the
      components of the speech stimulus that change rapidly over time; but not in the
      slower changing, lower frequency information in the stimulus. We demonstrate
      that, in agreement with the click-evoked brainstem response, females have earlier
      peaks relative to males in the subcomponents of the response representing the
      onset of the speech sound. In contrast, the response peaks comprising the
      frequency-following response, which encode the fundamental frequency (F(0)) of
      the stimulus, as well as the spectral amplitude of the response to the F(0), is
      not affected by sex. Notably, the higher-frequency elements of the speech
      syllable are encoded differently between males and females, with females having
      greater representation of spectrotemporal information for frequencies above the
      F(0). CONCLUSIONS: Our results provide a baseline for interpreting the higher
      incidence of language impairment (e.g. dyslexia, autism, specific language
      impairment) in males, and the subcortical deficits associated with these
      disorders. SIGNIFICANCE: These results parallel the subcortical encoding patterns
      that are documented for good and poor readers in that poor readers differ from
      good readers on encoding fast but not slow components of speech. This parallel
      may thus help to explain the higher incidence of reading impairment in males
      compared to females.

PMID- 21855411
TI  - Enhancer-promoter communication and transcriptional regulation of Igh.
AB  - Transcriptional regulation of eukaryotic protein-coding genes requires the
      participation of site-specific transcription factors that bind distal regulatory
      elements, as well as factors that, together with RNA polymerase II, form the
      basal transcription machinery at the core promoter. Gene regulation requires
      proper communication between promoters and enhancers, often over great distances.
      Therefore, it is important to understand the potentially inter-related
      transcription factor interactions at both of these elements. How this is achieved
      on tissue-specific genes, such as the immunoglobulin heavy chain (IgH) in B cells
      remains unclear. Here, we review known interactions at the Igh variable region
      (V(H)) promoters and present our perspective on promoter-enhancer interactions
      that are likely important for Ig gene regulation in B cells.

PMID- 21855412
TI  - Knowledge and perceived risks in couples undergoing genetic testing after
      recurrent miscarriage or for poor semen quality.
AB  - Couples with recurrent miscarriage (RM) and men with poor semen quality may
      undergo genetic testing as part of the diagnostic work-up. This study explored
      their knowledge and perception of genetic testing, evaluated psychological
      wellbeing and identified associated variables. A prospective questionnaire study
      was conducted in seven clinical genetics centres and referring gynaecological
      departments in couples with RM or poor semen quality. Questionnaires were
      completed before disclosure of genetic test results. Main outcome measures were
      knowledge, perceived risk, anxiety and depression. Of 439 participants, 256 were
      not aware genetic testing was part of the diagnostic work-up. One-third (36% RM,
      33% poor semen quality) indicated they had not received information about the
      genetic test from their doctor. Perceived risk of receiving an abnormal genetic
      test result was higher than objective risk. Anxiety was highly correlated with
      perceived risk. Women with RM were more anxious than women in the poor semen
      quality group or men (P<0.01). These couples undergoing genetic testing have a
      suboptimal understanding of the nature of testing, overestimate the risks of
      receiving an abnormal result and some show high levels of anxiety. The results of
      this study can be used to improve patient counselling before genetic testing.

PMID- 21855413
TI  - Infectious diseases biobanking as a catalyst towards personalized medicine:
      Mycobacterium tuberculosis paradigm.
AB  - Research for biomarkers supporting personalized medicine in infectious diseases
      is needed, especially for tuberculosis in which the existing toolbox does not yet
      address the public health priorities. Biobanks are essential infrastructures in
      this effort by collecting, authenticating and preserving human and/or bacterial
      specimens. A broad range of specimens should be collected prior to, during and
      following treatment, with a comprehensive characterisation of the sample donors
      and the samples themselves to accommodate the most recent technological platforms
      in biomarker research. This review explains current state-of-the-field biobanking
      practices in tuberculosis and suggests technical and managerial improvements to
      ensure long-term preservation and optimal use of the specimens. Open-access and
      certified biobanks are an essential component of a strategy supporting the
      development of drugs and diagnostic tests for both public health and personalised
      medicine. Biobanks have a role to play in the interaction between these two - not
      always compatible - approaches.

PMID- 21855414
TI  - Case report: blastic Mantle Cell Leukemia.
AB  - The patient, who was being followed up for Mantle Cell Lymphoma, was diagnosed
      with Mast Cell Leukemia 2 years after receiving R-CHOP treatment. The results of
      flow cytometry, which was performed upon determining leucocytosis and detecting
      blasts in the peripheral smear following the patient's presentation due to his
      poor general condition, was consistent with Mantle Cell Leukemia. This case is
      being presented since there are a very limited number of previously published
      cases on this topic.

PMID- 21855415
TI  - Delayed ileal-ileocystoplasty fistula formation: an unusual complication of
      augmentation enterocystoplasty.
AB  - Augmentation enterocystoplasty is a successful treatment for patients with
      neurogenic bladder dysfunction. Delayed spontaneous bladder rupture is a serious
      recognised complication of the procedure; however, to our knowledge, delayed
      fistula formation between the neobladder and the gastrointestinal tract has not
      been reported in the literature. We report the case of a 21-year-old male who
      presented with chronic diarrhoea resulting from an ileal-ileocystoplasty fistula
      10 years following a successful augmentation enterocystoplasty. Fistula formation
      is a possible complication of this procedure, and a high index of suspicion is
      required for patients presenting with diarrhoea who have previously undergone
      bladder augmentation surgery.

PMID- 21855416
TI  - Familiarizing with toy food: preliminary research and future directions.
AB  - OBJECTIVE: A qualitative content analysis of children and parents interacting
      with toy food in their homes in view of recommendations for developing healthful
      food preferences. METHODS: YouTube videos (n = 101) of children and parents
      interacting in toy kitchen settings were analyzed using qualitative content
      analysis. Toy food was categorized under 5 food groups, and interactions were
      compared to literature on developing healthful food preferences in children in
      real life. RESULTS: The most popular food group represented by the toys was
      Extras, followed by Fruits/Vegetables, Meats/Alternatives, Grains, and
      Milk/Dairy. Many parents were also found to encourage behaviors not conducive to
      healthful food preference development in children. CONCLUSIONS AND IMPLICATIONS:
      Future research needs to determine whether familiarization with toy food
      influences children's real-life food preferences. Nutrition education programs
      for young children and parents could greatly benefit from future research on this
      approach. Exploring novel ways of developing children's food preferences is well
      warranted.

PMID- 21855417
TI  - Household food security and fruit and vegetable intake among low-income fourth
      graders.
AB  - OBJECTIVE: To examine the relationship between household food security and
      children's and parents' fruit, vegetable, and breakfast consumption and fruit and
      vegetable availability. DESIGN: Cross-sectional study using matched parent-child
      surveys. SETTING: Title I elementary schools in Maryland. PARTICIPANTS: Ninety
      two low-income parent-child dyads recruited from fourth-grade nutrition education
      programs completing a baseline evaluation. MAIN OUTCOME MEASURES: Fruit and
      vegetable intake, breakfast consumption, and fruit and vegetable availability in
      home and school. ANALYSIS: Chi-square tests, 1-way ANOVA. RESULTS: Thirty-six
      percent of parents reported low/very low household food security, and both
      parents and students reported low fruit and vegetable intake. Students from
      households with low food security who were not participating in school nutrition
      programs had the lowest vegetable consumption and the fewest number of days
      consuming breakfast, indicating a relatively greater need for enrollment than
      their peers. CONCLUSIONS AND IMPLICATIONS: Few differences between children in
      food-secure and food-insecure households were observed, which underscores the
      need for research on food insecurity and children's eating behaviors. Examination
      of other factors influencing fruit and vegetable intake and improvements in food
      environments and programs are needed. Efforts to increase enrollment among
      eligible students in school nutrition programs may reduce negative consequences
      of household food insecurity.

PMID- 21855418
TI  - One-year seizure prognosis in epilepsy patients treated with antidepressants.
AB  - To investigate the clinical effects of antidepressants on seizure frequency of
      patients with epilepsy treated with antiepileptic drugs, we retrospectively
      evaluated the 1-year course of seizure frequency. One hundred twenty-one patients
      with epilepsy treated with antidepressants and 300 patients with epilepsy not
      treated with antidepressants (controls) were the subjects of this study. Seizure
      frequency over the 1-year period of administration of antidepressants was
      retrospectively evaluated and compared with that for controls. In the patients
      with epilepsy taking antidepressants, seizure frequencies at four observation
      points (1, 3, 6, and 12 months after starting antidepressants) were equivalent to
      those of the control group. There was no significant difference in seizure
      frequency between first- and second-generation antidepressants. Patients with
      epilepsy treated with antiepileptic drugs can take antidepressants without a
      significant risk of exacerbation of seizures. Most antidepressants can be used
      for psychiatric treatment of patients with epilepsy.

PMID- 21855419
TI  - Usefulness of verbal selective reminding in distinguishing frontal lobe memory
      disorders in epilepsy.
AB  - Frontal lobe memory disorders are distinguished from hippocampal memory disorders
      by poor organization of encoding and retrieval, among other things. Because the
      verbal Selective Reminding Test (SRT) has a metamemory ("remembering-to
      remember") component, it may be useful in distinguishing frontal from temporal
      lobe memory disorders in patients with intractable epilepsy. Thirty-four patients
      with frontal lobe epilepsy (FLE) and 34 with temporal lobe epilepsy (TLE)
      underwent a comprehensive neuropsychological evaluation that included multiple
      memory and executive function tests. Patients with FLE performed significantly
      worse than those with TLE on SRT measures and Wechsler Memory Scale, Third
      Edition, Logical Memory (LM II), but not on other verbal and nonverbal memory
      tests. Furthermore, SRT and LM-II were significantly correlated with executive
      function measures. These findings have both theoretical and practical
      implications: (1) the memory impairment observed in frontal lobe disorders may be
      due, in part, to deficits in organizational strategy, monitoring, and remembering
      to-remember, and (2) SRT and LM-II may be useful tests to differentiate frontal
      from temporal lobe memory disorders.

PMID- 21855420
TI  - Ten-year subjective outcome results of the retropubic tension-free vaginal tape
      for treatment of stress urinary incontinence.
AB  - STUDY OBJECTIVE: To assess the 10-year subjective outcome of use of retropubic
      tension-free vaginal tape (TVT). DESIGN: Structured telephone interview (Canadian
      Task Force classification II-3). SETTING: Universitiy-affiliated tertiary medical
      center. PATIENTS: Sixty consecutive women with urodynamically confirmed stress
      urinary incontinence (SUI) who underwent retropubic TVT surgery during 2000. At
      surgery, their mean (SD) age was 62.4 (9.3) years, and parity was 2.9 (1.3).
      INTERVENTIONS: Retropubic TVT, with 10-year subjective outcome questionaire.
      MEASUREMENTS AND MAIN RESULTS: Of the 60 patients, 52 (87%) were available for 10
      year follow-up. Preoperatively, all patients reported substantial SUI, and 28
      (54%) also had concomitant urge urinary incontinence (UUI). At 10 years
      postoperatively, 34 women (65%) considered their condition cured, 6 (12%)
      believed it was improved, and 12 (23%) thought surgery had failed. Eleven women
      (21%) reported SUI, 22 (42%) had UUI (de novo UUI in 9), and 8 (15%) had
      recurrent urinary tract infections. Two women (4%) underwent repeated TVT. Of the
      various perioperative variables, only postoperative impaired bladder emptying was
      a statistically independent risk factor for long-term failure (odds ratio, 6.4;
      95% confidence interval, 1.3-30.1). CONCLUSIONS: Ten-year subjective outcome of
      retropubic TVT are less favorable than previously reported. Early postoperative
      impaired bladder emptying is the most significant risk factor for long-term
      failure.

PMID- 21855421
TI  - Acute renal artery occlusion: making the case for renal artery revascularization.
AB  - Atherosclerotic renal artery disease is a common disease entity that may be
      identified in patients with difficult-to-control hypertension and/or chronic
      kidney disease but is probably underdiagnosed. Current evidence from both
      observational and randomized studies offers mixed results regarding the support
      for renal artery revascularization. There is lack of equipoise with regard to the
      efficacy of renal artery revascularization among the interventional and renal
      communities, as well as disagreements on the appropriate endpoints to measure in
      clinical trials, which have led to selection bias confounding the scant available
      data. We report a patient who does not fit any clinical trial inclusion criteria
      with acute on chronic kidney injury and new-onset heart failure whose symptoms
      and renal function improved significantly after renal artery intervention.

PMID- 21855422
TI  - TRPV1 expressing extrinsic primary sensory neurons play a protective role in
      mouse oxazolone-induced colitis.
AB  - TRPV1 expressing sensory neurons which have been considered to be largely
      associated with neurogenic inflammation were chemically denervated by capsaicin
      treatment in neonatal mice. However, neonatal capsaicin treatment aggravated
      mouse oxazolone-induced colitis, and did not affect the expression of calcitonin
      gene-related peptide (CGRP)- or substance P-immunoreactive nerve fibers in the
      colon. Meanwhile, the capsaicin-induced contraction was absent in the colon of
      neonatal capsaicin treatment mouse. These results suggest a protective role of
      TRPV1 expressing extrinsic sensory neurons in oxazolone-induced colitis and the
      involvement of some neurotransmitter other than CGRP and substance P in the
      pathogenesis of the colitis.

PMID- 21855423
TI  - Clinical practices for intermediate sweat tests following abnormal cystic
      fibrosis newborn screens.
AB  - BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) has become standard
      practice in many countries. Consequently, the prevalence of infants with
      intermediate sweat test results has increased. This study examined clinical
      practices in the United States (US) related to intermediate sweat test results
      subsequent to NBS. METHODS: Respondents from 77 (47% response rate) US CF centers
      completed telephone surveys documenting clinical practices related to
      intermediate sweat chloride levels (30-59 mmol/L) following abnormal NBS.
      RESULTS: Thirty percent of centers followed CF Foundation guidelines for
      classifying intermediate results. There was much variability in sweat testing
      procedures, diagnostic labels, additional diagnostics, addressing prognosis, and
      services offered to parents. CF center staff identified a need for resources to
      better address the uncertainty associated with intermediate results. CONCLUSION:
      Results suggest the need for education regarding current guidelines and consensus
      regarding the nomenclature and services offered to families of newborns with
      intermediate sweat test results.

PMID- 21855424
TI  - Simultaneous free and glycosylated pyridinium crosslink determination in urine:
      validation of an HPLC-fluorescence method using a deoxypyridinoline homologue as
      internal standard.
AB  - Pyridinoline (Pyr), deoxypyridinoline (D-Pyr), galactosyl-pyridinoline (Gal-Pyr)
      and glucosyl-galactosyl pyridinoline (GluGal-Pyr) are enzymatic mature pyridinium
      crosslinks. Generally, only total Pyr and D-Pyr urinary amounts (free+bound
      forms) are evaluated by HPLC as indices of bone resorption. This report describes
      the validation of an HPLC-fluorescence method for the simultaneous evaluation of
      free Pyr and D-Pyr, together with GluGal-Pyr and Gal-Pyr, in urine of healthy
      women (n=20, aged 27-41) and girls (n=20, aged 5-10). The use of an unnatural D
      Pyr homologue, here proposed for the first time as internal standard, and of pure
      Pyr, D-Pyr, GluGal-Pyr and Gal-Pyr synthesized to be used as primary calibrators,
      guarantees method specificity and correct crosslink quantification. Urine, spiked
      with IS, was solid-phase extracted prior to HPLC analysis. Total Pyr and D-Pyr
      amounts were also evaluated after urine hydrolysis. The HPLC method was validated
      for selectivity, sensitivity, linearity, precision, accuracy, recovery and
      stability for all measured crosslinks. Both free and total Pyr and D-Pyr as well
      as GluGal-Pyr and Gal-Pyr amounts were significantly higher in girls than in
      women (p<0.0001), indicating an increased collagen turnover rather than only bone
      turnover. Gal-Pyr, for the first time evaluated in girls, was under its lower
      quantification limit (<LLOQ, <21.20 pmol/mL) in women. The measurement of free
      and glycosylated pyridinium crosslinks might provide more information on the
      degradation of various types of collagen than only that of total Pyr and D-Pyr.
      Moreover, this validated method could be a useful non-invasive technique for
      studying pathological conditions characterized by modified glycosylation enzyme
      activity and for more clinical investigation on bone fragility.

PMID- 21855425
TI  - Simultaneous determination of urinary tryptophan, tryptophan-related metabolites
      and creatinine by high performance liquid chromatography with ultraviolet and
      fluorimetric detection.
AB  - A high performance liquid chromatography method with ultraviolet and fluorimetric
      detection has been developed for the simultaneous determination of urinary
      creatinine (Cr), tryptophan (Trp) and three Trp-related metabolites including
      kynurenine (Kyn), kynurenic acid (Kyna) and 5-hydroxyindole-3-acetic acid (5
      HIAA). Samples were pretreated by centrifugation after a freeze-thaw cycle to
      remove protein and other precipitates. Separation was achieved by an Agilent HC
      C18 (2) analytical column and a gradient elution program with a constant flow
      rate 1mL/min at an ambient temperature. Total run time was 30 min. Cr, Kyn and
      Kyna were measured by a variable wavelength detector at wavelengths 258 nm, 365
      nm and 344 nm respectively. Trp and 5-HIAA were measured by a fluorescence
      detector with an excitation wavelength of 295 nm and an emission wavelength of
      340 nm. This allowed the determination of Kyn/Cr, Kyna/Cr, Trp/Cr and 5-HIAA/Cr
      concentration ratios in a single run on the same urine sample. Good linear
      responses were found with correlation coefficient (r)>0.999 for all analytes
      within the concentration range of physiological level. The limit of detection of
      the developed method was: Cr, 0.0002 g/L; Kyn, 0.1 MUmol/L; Kyna, 0.04 MUmol/L;
      Trp, 0.02 MUmol/L and 5-HIAA, 0.01 MUmol/L. Recoveries from spiked human urine
      were: Cr, 93.0-106.4%; Kyn, 97.9-106.9%; Kyna, 98.5-105.6%; Trp, 96.7-105.2% and
      5-HIAA, 96.1-99.7%. CVs of repeatability and intermediate precision of all
      analytes were less than 5%. This method has been applied to the analysis of urine
      samples from normal subjects.

PMID- 21855426
TI  - Ultra-performance liquid chromatography-tandem mass spectrometric method for the
      determination of strychnine and brucine in mice plasma.
AB  - A selective, simple and efficient method-ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) was developed for determination of two
      toxic alkaloids, namely strychnine and brucine in mice plasma. The UPLC
      separation was carried out using a 1.7 MUm BEH C(18) column (50 mm * 2.1 mm) with
      a mobile phase consisting of methanol:0.1% formic acid (25:75, v/v), hence
      providing high efficiency, high resolution and excellent peak shape for the
      analytes and internal standard. The method was validated over the range of 2.48
      496.4 ng/ml for strychnine and 2.64-528 ng/ml for brucine, respectively. Intra-
      and inter-day accuracy ranged from 95.0% to 107.9% for strychnine, 93.4% to
      103.3% for brucine, and the precisions were within 13.8%. The extraction
      recoveries of both the two alkaloids exceed 81.9%. With a simple and minor sample
      preparation procedure and short run-time (<3 min), the proposed method was
      applicable for the pharmacokinetic and toxicological analysis of strychnine and
      brucine in vivo.

PMID- 21855429
TI  - Clinical significance of Mycobacterium abscessus isolates at a medical center in
      Northern Taiwan.

PMID- 21855427
TI  - Increases in mitochondrial biogenesis impair carcinogenesis at multiple levels.
AB  - Although mitochondrial respiration is decreased in most cancer cells, the role of
      this decrease in carcinogenesis and cancer progression is still unclear. To
      better understand this phenomenon, instead of further inhibiting mitochondrial
      function, we induced mitochondrial biogenesis in transformed cells by activating
      the peroxisome proliferator-activated receptors (PPARs)/peroxisome proliferator
      activated receptor gamma co-activator 1alpha (PGC-1alpha) pathways. This was
      achieved by treating the cells with bezafibrate, a PPARs panagonist that also
      enhances PGC-1alpha expression. We confirmed that bezafibrate treatment led to
      increased mitochondrial proteins and enzyme functions. We found that cells with
      increased mitochondrial biogenesis had decreased growth rates in glucose
      containing medium. In addition, they became less invasive, which was directly
      linked to the reduced lactate levels. Surprisingly, even though bezafibrate
      treated cells had higher levels of mitochondrial markers, total respiration was
      not significantly altered. However, respiratory coupling, and ATP levels were.
      Our data show that by increasing the efficiency of the mitochondrial oxidative
      phosphorylation system, cancer progression is hampered by decreases in cell
      proliferation and invasiveness.

PMID- 21855430
TI  - Diagnostic performance of enzyme-linked immunospot assay and whole-blood
      interferon-gamma assay for the diagnosis of extrapulmonary tuberculosis.

PMID- 21855431
TI  - [Measuring tidal volume during paediatric oscillatory and jet high-frequency
      ventilation].
AB  - OBJECTIVE: To ascertain whether a spirometer can measure tidal volume (TV) during
      high frequency oscillatory ventilation (HFOV) and high frequency jet ventilation
      (HFJV), and to analyse the effect of changes in ventilator settings. METHODS: The
      study was performed with paediatric porcine lung models submitted to HFOV with a
      Sensormedics 3100 ventilator and HFJV with a Paravent Pat(e)(R) ventilator
      connected to a D-Fend spirometer. Programmed frequency, amplitude, and mean
      airway pressure (MAP) were changed in the ventilator, and TV and pressures were
      recorded using the spirometer. RESULTS: The spirometer measured TV in the
      paediatric lung models and piglets, but could not measure TV less than 8 ml, when
      the pressure amplitude was higher than 55 cmH(2)O or the MAP was higher than 30
      cmH(2)O. With HFOV there was a correlation between amplitude and tidal volume,
      and a positive correlation between pressure and TV with HFJV. With both
      respirators there was a negative correlation between frequency and TV.
      CONCLUSIONS: The D-Fend spirometer can measure tidal volume and pressure during
      HFOV and HFJV. However, it does not work with volumes lower than 8 ml, and high
      amplitude or mean airway pressure.

PMID- 21855432
TI  - [Cutaneous larva migrans: presentation of a case].

PMID- 21855433
TI  - The impact of exposure to images of ideally thin models in TV commercials on
      eating behavior: an experimental study with women diagnosed with bulimia nervosa.
AB  - This study investigates whether eating behavior in women with diagnosed bulimia
      nervosa is influenced by prior exposure to images of ideally thin models. Twenty
      six participants diagnosed with bulimia nervosa (BN) and 30 normal controls (NC)
      were exposed to body-related and neutral TV commercials; then food that typically
      triggers binge eating was provided, and the amount of food eaten was measured. No
      significant difference for food intake between NC and BN could be found, but food
      intake for BN was predicted by the degree of thoughts related to eating behaviors
      during exposure to the thin ideal. No impact of general body image or eating
      pathology on food intake could be found. The results emphasize the importance of
      action-relevance of dysfunctional cognitions for the maintenance of eating
      disordered behaviors in women with bulimia nervosa, when exposed to eating
      disorder-specific triggers.

PMID- 21855434
TI  - Young men's coping with androgenetic alopecia: acceptance counts when hair gets
      thinner.
AB  - The present study examined how young men cope with balding (androgenetic
      alopecia). The sample consisted of 160 university students (18-30 years) with
      varying degrees of hair loss (stages II-VII on the Norwood-Hamilton Scale). Three
      ways of coping were distinguished: compensation, avoidance, and acceptance.
      Psychological distress due to hair loss depended neither on the age of
      participants nor on the stage of balding. Since compensation and avoidance were
      associated with high levels of distress, their functional value might be
      questioned. Acceptance, however, was negatively related to distress--even, or
      rather, especially when stage of hair loss was advanced. Furthermore, acceptance
      had a direct negative effect on medical consultation about hair loss. By
      contrast, compensation and avoidance had a positive distress-mediated effect on
      medical consultation. Taken together, this study underlines the adaptive role of
      acceptance when confronted with irreversible changes such as androgenetic
      alopecia.

PMID- 21855436
TI  - A novel technique for securing the catheter post hypospadias surgery.

PMID- 21855435
TI  - Perinatal inflammation and lung injury.
AB  - Bronchopulmonary dysplasia (BPD) remains the major morbidity of extreme preterm
      birth. The incidence of BPD has remained stable despite recent efforts to reduce
      postnatal exposures to volutrauma and hyperoxia. This review will focus on recent
      clinical and experimental insights that provide support for the concept that the
      'new BPD' is the result of inflammation-mediated injury and altered lung
      development during a window of vulnerability in genetically susceptible infants
      that is modified by maternal and postnatal exposures.

PMID- 21855437
TI  - The effect of abdominal wall plication on intra-abdominal pressure and lower
      extremity venous flow: a case report.
AB  - Abdominal wall plication is known to cause increased intra-abdominal pressure
      (IAP). Whether plication-associated increased IAP causes lower extremity venous
      stasis, a recognized risk factor for DVT, remains unknown. A 55-year-old woman
      had a unilateral pedicled TRAM procedure for mastectomy reconstruction. Prior to
      plication, duplex ultrasound measured proximal femoral vein (PFV) cross-sectional
      diameter and volume-flow. PFV measurements were repeated immediately after
      plication and on post-operative days (POD) 1, 2, and 4. Bladder pressure was
      measured at similar timepoints. PFV volume-flow decreased from 0.22 L/min to 0.16
      L/min (73% of baseline) immediately post-plication and reached a nadir of 0.08
      L/min (36% of baseline) on POD 2. Bladder pressure increased from 13 mm Hg to 19
      mm Hg after plication, and peaked at 31 mm Hg after intra-operative trunk flexion
      to 30 degrees . Thus, abdominal wall plication was associated with increased
      intra-abdominal pressure and ultrasound-documented lower extremity venous stasis
      that persisted for 48 h after surgery.

PMID- 21855438
TI  - Severe periodontitis and orthodontics: evaluation of long-term results.
AB  - Clinical manifestations of severe periodontitis are very often associated with
      tooth migration. The aim of this retrospective study is to evaluate dental bone
      support before orthodontic-periodontal treatment, at immediate postoperative, and
      long-term postoperative and to compare these results with those obtained from
      periodontal treatment alone. Fifteen patients (11 women and four men), all with
      severe periodontitis, mean age 42.8 years (22-61), were followed for an average
      of 16 years (11-32). Comparison was made between periodontal-orthodontic
      treatment (Group 1) and periodontal treatment alone (Group 2). Alveolar bone
      height was measured at T0 (before treatment), T1 (immediate postoperative) and T2
      (long-term postoperative). Assessment was performed by means of digitized
      radiography using Image J Software from the National Institute of Health. The
      average postoperative observation period between T0 (before treatment) and T2
      (long-term results) was 16 years (11 to 32). Results showed an overall bone
      apposition in groups (1 and 2) immediately after treatment (T1), then at long
      term (T2). No statistical difference was observed between both groups (1 and 2).
      IN CONCLUSION: an overall bone gain was observed in both treatment groups
      (periodontal-orthodontic and periodontal alone). The orthodontic treatment
      combined with periodontal treatment never compromised the benefits of periodontal
      treatment alone. On the opposite, it appeared to be quite beneficial.

PMID- 21855441
TI  - Assessment of quality of life in stroke patients with hemiplegia.
AB  - Stroke is a major public health issue. Even though most hemiplegic stroke
      patients may obtain a good functional outcome, many remain dissatisfied with
      their lives. Indeed, quality of life and subjective well-being should be taken
      into account in any assessment of stroke survival. OBJECTIVE: To assess long-term
      quality of life in stroke patients (compared with healthy controls) and the
      corresponding determinants and predictive factors. METHOD: The patient population
      consisted of 80 of the 217 first-stroke survivors treated between January and
      June 2005 in the Clinical Neurosciences Department at Bordeaux University
      Hospital. After a mean follow-up period of 2 years, 24 patients were interviewed
      in their homes and data from the 56 others were obtained in a telephone
      interview. Demographic information, clinical status on admission and functional
      status (as assessed by Barthel Index) and depression (on the ADRS) at the time of
      the study visit were recorded. Quality of life was assessed by using the Sickness
      Impact Profile (SIP-65) and Branholm and Fugl-Meyer's Satisfaction with Life
      Scale (LiSat 11). The patients' data were compared with those from 149 healthy
      controls. RESULTS: Life satisfaction and quality of life were significantly
      impaired in stroke patients, compared with controls. All life domains were
      impaired. The worst scores were observed for independence and health-related
      items in the LiSat 11 and the physical and communication items in the SIP-65.
      Quality of life was strongly correlated with functional independence, the
      persistence of hemiplegia and depressive mood, which is in agreement with
      literature findings. Neither gender nor the initial Rankin score had a
      significant impact on these parameters. DISCUSSION-CONCLUSION: Quality of life at
      2 years is significantly impaired in stroke survivors and seems more difficult to
      predict than functional independence. However, in addition to these objective
      results, our interviews suggest that receiving adequate social support might be
      as important to patients as recovering independence.

PMID- 21855442
TI  - Laparoscopic lumbo-aortic lymph node dissection.

PMID- 21855518
TI  - Acute hepatitis E infection accounts for some cases of suspected drug-induced
      liver injury.
AB  - BACKGROUND & AIMS: The diagnosis of drug-induced liver injury relies on exclusion
      of other causes, including viral hepatitis A, B, and C. Hepatitis E virus (HEV)
      infection has been proposed as another cause of suspected drug-induced liver
      disease. We assessed the frequency of HEV infection among patients with drug
      induced liver injury in the United States. METHODS: The Drug-Induced Liver Injury
      Network (DILIN) is a prospective study of patients with suspected drug-induced
      liver injury; clinical information and biological samples are collected to
      investigate pathogenesis and disease progression. We analyzed serum samples,
      collected from patients enrolled in DILIN, for immunoglobulin (Ig) G and IgM
      against HEV; selected samples were tested for HEV RNA. RESULTS: Among 318
      patients with suspected drug-induced liver injury, 50 (16%) tested positive for
      anti-HEV IgG and 9 (3%) for anti-HEV IgM. The samples that contained anti-HEV IgM
      (collected 2 to 24 weeks after onset of symptoms) included 4 that tested positive
      for HEV RNA genotype 3. Samples from the 6-month follow-up visit were available
      from 4 patients; they were negative for anti-HEV IgM, but levels of anti-HEV IgG
      increased with time. Patients who had anti-HEV IgM were mostly older men (89%;
      mean age, 67 years), and 2 were human immunodeficiency virus positive. Clinical
      reassessment of the 9 patients with anti-HEV IgM indicated that acute hepatitis E
      was the most likely diagnosis for 7 and might be the primary diagnosis for 2.
      CONCLUSIONS: HEV infection contributes to a small but important proportion of
      cases of acute liver injury that are suspected to be drug induced. Serologic
      testing for HEV infection should be performed, particularly if clinical features
      are compatible with acute viral hepatitis.

PMID- 21855519
TI  - Clinical and electrocardiographic characteristics of patients with short QT
      interval in a large hospital-based population.
AB  - BACKGROUND: Short QT syndrome is one of the underlying disorders associated with
      ventricular fibrillation. However, the precise prognostic implication of a short
      QT interval remains unclear. OBJECTIVE: The purpose of this study was to
      investigate the prevalence and long-term prognosis in patients with a shorter
      than-normal QT interval in a large hospital-based population. METHODS: We chose
      patients with a short Bazett QTc interval from a database consisting of 114,334
      patients to determine the clinical characteristics and prognostic value of a
      short QT interval. RESULTS: A total of 427 patients (mean age 43.4 +/- 22.4
      years) had a short QT interval with about a 1.2 times higher male predominance
      (234 men). The QTc interval was significantly longer in female than in male
      patients (363.8 +/- 6.1 ms vs 357.1 +/- 5.8 ms, P <.0001). The age-specific
      prevalence of patients with short QT interval was biphasic, peaking at young and
      old age. Atrial fibrillation and early repolarization were complicated with short
      QT interval in 39 (9.1%) and 26 (6.1%) patients, respectively. The prognosis of
      327 patients (182 men; mean age, 46.4 +/- 27.3 years) with a short QT interval
      could be assessed (mean follow-up period, 54.0 +/- 62.0 months). During the
      follow-up, 2 patients, 1 of whom had early repolarization, developed life
      threatening events, in contrast to 6 patients who died of noncardiac causes and
      did not have early repolarization. CONCLUSION: The prevalence of a short QT
      interval showed a slight male preponderance and biphasic age-dependent
      distribution in both genders. The complication rate of atrial fibrillation was
      higher in those with a short QT interval than in general populations. The long
      term outcome suggested that early repolarization in a short QT interval might be
      associated with potential risk of lethal arrhythmia.

PMID- 21855520
TI  - Bi-stable wave propagation and early afterdepolarization-mediated cardiac
      arrhythmias.
AB  - BACKGROUND: In normal atrial and ventricular tissue, the electrical wavefronts
      are mediated by the fast sodium current (I(Na)), whereas in sinoatrial and
      atrioventricular nodal tissue, conduction is mediated by the slow L-type calcium
      current (I(Ca,L)). However, it has not been shown whether the same tissue can
      exhibit both the I(Na)-mediated and the I(Ca,L)-mediated conduction. OBJECTIVE:
      This study sought to test the hypothesis that bi-stable cardiac wave conduction,
      mediated by I(Na) and I(Ca,L), respectively, can occur in the same tissue under
      conditions promoting early afterdepolarizations (EADs), and to study how this
      novel wave dynamics is related to the mechanisms of EAD-mediated arrhythmias.
      METHODS: Computer models of two-dimensional (2D) tissue with a physiologically
      detailed action potential model were used to study the bi-stable wave dynamics.
      Theoretical predictions were tested experimentally by optical mapping in neonatal
      rat ventricular myocyte monolayers. RESULTS: In the same 2D homogeneous tissue,
      we could induce spiral waves that are mediated by either I(Na) or I(Ca,L) under
      conditions in which the action potential model exhibited EADs. This bi-stable
      wave propagation behavior was similar to bi-stability shown in many other
      nonlinear systems. Because the bi-stable states are also excitable, we call this
      novel behavior bi-excitability. In a 2D heterogeneous tissue, the I(Ca,L)
      mediated spiral wave meanders, giving rise to a twisting electrocardiographic QRS
      axis, resembling torsades de pointes, whereas the coexistence and interplay
      between the I(Na)-mediated wavefronts and I(Ca,L)-mediated wavefronts give rise
      to polymorphic ventricular tachycardia. We also present experimental evidence for
      bi-excitability under EAD-promoting conditions in neonatal rat ventricular
      myocyte monolayers exposed to BayK8644 and isoproterenol. CONCLUSION: Under EAD
      prone conditions, both I(Na)-mediated conduction and I(Ca,L)-mediated conduction
      can occur in the same tissue. These novel wave dynamics may be responsible for
      certain EAD-mediated arrhythmias, such as torsades de pointes and polymorphic
      ventricular tachycardia.

PMID- 21855521
TI  - Effect of sodium-channel blockade on early repolarization in inferior/lateral
      leads in patients with idiopathic ventricular fibrillation and Brugada syndrome.
AB  - BACKGROUND: A high incidence of early repolarization (ER) pattern in the
      inferolateral leads has been reported in patients with idiopathic ventricular
      fibrillation (IVF). Brugada syndrome (BS) is characterized by J-point or ST
      segment elevation in the right precordial leads and ventricular fibrillation, and
      some patients with BS also have ER in the inferolateral leads. OBJECTIVE: To
      compare the clinical characteristics and effects of sodium-channel blockade on ER
      between IVF patients with ER (early repolarization syndrome [ERS]) and BS
      patients with or without ER. METHODS: Fourteen patients with ERS and 21 patients
      with BS were included in this study. ER was defined as an elevation of at least
      0.1 mV from baseline in the QRS-T junction in the inferorolateral leads.
      Provocative tests with sodium-channel blockers were conducted in all patients
      with ERS to distinguish ERS from BS. RESULTS: In the ERS group, all patients were
      male and most patients experienced ventricular fibrillation during sleep or low
      activity (79%). ER was attenuated by sodium-channel blockers in most patients
      with ERS (13/14, 93%) and BS (5/5, 100%), whereas ST-segment elevation was
      augmented in the right precordial leads in the BS group. The rates of positive
      late potentials were significantly higher in the BS group (60%) than in the ERS
      group (7%) (P <.01). CONCLUSIONS: Some similarities were observed between ERS and
      BS, including gender, arrhythmia triggers, and response of ER to sodium-channel
      blockers. Unlike the ST segment in the right precordial leads in BS, ER was
      attenuated in patients with both ERS and BS, suggesting a differential mechanism
      between ER in the inferolateral leads and ST elevation in the right precordial
      leads.

PMID- 21855522
TI  - Relation of symptoms and symptom duration to premature ventricular complex
      induced cardiomyopathy.
AB  - BACKGROUND: Frequent idiopathic premature ventricular complexes (PVCs) can result
      in a reversible form of cardiomyopathy. In this study, the determinants of PVC
      induced left ventricular (LV) dysfunction were assessed. METHODS: The subjects of
      this study were 241 consecutive patients (115 men [48%], mean age 48 +/- 14
      years) referred for ablation of frequent PVCs. One hundred eighty patients (75%)
      experienced palpitations and 61 (25%) did not. The PVC burden was determined by
      24-hour Holter monitoring, and echocardiograms were performed to assess LV
      function. An LV ejection fraction of <50% was considered abnormal. RESULTS: LV
      ejection fraction (mean 0.36 +/- 0.09) was present in 76 of 241 patients (32%).
      There was a higher prevalence of males among the patients with PVC cardiomyopathy
      compared to patients with normal LV function (51/76 [67%] vs 64/165 [39%]; P
      <.0001). The mean PVC burden was significantly higher in patients with PVC
      cardiomyopathy than in patients with normal LV function (28% +/- 12% vs 15% +/-
      13%; P <.0001). Among symptomatic patients, those with cardiomyopathy had a
      significantly longer duration of palpitations (135 +/- 118 months) compared with
      patients with normal LV function (35 +/- 52 months; P <.0001). The proportion of
      asymptomatic patients was significantly higher in the presence of cardiomyopathy
      (36/76, 47%) than in normal LV function (25/165, 15%; P <.0001). Symptom duration
      of 30 to 60 months, symptom duration >60 months, the absence of symptoms, and the
      PVC burden in asymptomatic patients were independent predictors of impaired LV
      function (adjusted odds ratio [95% confidence interval]: 4.0 [1.1-14.4], 20.1
      [6.3-64.1], 13.1 [4.1-37.8], and 2.1 [1.2-3.6], respectively). CONCLUSIONS: The
      duration of palpitations and the absence of symptoms are independently associated
      with PVC-induced cardiomyopathy.

PMID- 21855523
TI  - Trypanosoma cruzi I-III in southern Brazil causing individual and mixed
      infections in humans, sylvatic reservoirs and triatomines.
AB  - The aim of this study was to characterise Discrete Typing Units (DTUs) of 28
      isolates of Trypanosoma cruzi from humans (15), triatomines (9), and opossums (4)
      in the state of Parana, southern Brazil. For this purpose, we analysed the size
      polymorphism at the 3' end of the 24Salpha ribosomal RNA gene (rRNA) and the
      restriction fragment length polymorphism (RFLP) of the partial 5' sequence of the
      mitochondrial Cytochrome Oxidase subunit II gene (COII). Band patterns of the
      isolates were compared with reference samples of T. cruzi I (Silvio X10 and Col
      17G2), T. cruzi II (Esmeraldo and JG), T. cruzi III (222 and 231), T. cruzi IV
      (CAN III), T. cruzi V (SO3 cl5), and T. cruzi VI (CL Brener). Our results
      confirmed that rRNA analysis is of limited use for assessing T. cruzi DTUs. COII
      RFLP analysis was suitable for screening, but for one isolate it was necessary to
      determine the COII partial sequence to identify the DTU. Only one of the isolates
      from humans belonged to T. cruzi I; 13 isolates belonged to T. cruzi II and one
      to T. cruzi III. The four isolates from opossums and five isolates from
      triatomines were identified as T. cruzi I. Four isolates from triatomines showed
      patterns of both T. cruzi I and II, indicating mixed infections. This study
      contributes to the characterisation of the dynamics of T. cruzi populations in
      southern Brazil.

PMID- 21855524
TI  - Sequential abundant ion fragmentation analysis (SAIFA): an alternative approach
      for phosphopeptide identification using an ion trap mass spectrometer.
AB  - Phosphorylation has been the most studied of all the posttranslational
      modifications of proteins. Mass spectrometry has emerged as a powerful tool for
      phosphomapping on proteins/peptides. Collision-induced dissociation (CID) of
      phosphopeptides leads to the loss of phosphoric or metaphosphoric acid as a
      neutral molecule, giving an intense neutral loss product ion in the mass
      spectrum. Dissociation of the neutral loss product ion identifies peptide
      sequence. This method of data-dependent constant neutral loss (DDNL) scanning
      analysis has been commonly used for mapping phosphopeptides. However,
      preferential losses of groups other than phosphate are frequently observed during
      CID of phosphopeptides. Ions that result from such losses are not identified
      during DDNL analysis due to predetermined scanning for phosphate loss. In this
      study, we describe an alternative approach for improved identification of
      phosphopeptides by sequential abundant ion fragmentation analysis (SAIFA). In
      this approach, there is no predetermined neutral loss molecule, thereby
      undergoing sequential fragmentation of abundant peak, irrespective of the moiety
      lost during CID. In addition to improved phosphomapping, the method increases the
      sequence coverage of the proteins identified, thereby increasing the confidence
      of protein identification. To the best of our knowledge, this is the first report
      to use SAIFA for phosphopeptide identification.

PMID- 21855525
TI  - Polyphenol biosensor based on laccase immobilized onto silver
      nanoparticles/multiwalled carbon nanotube/polyaniline gold electrode.
AB  - Laccase purified from Ganoderma sp. was immobilized covalently onto
      electrochemically deposited silver nanoparticles (AgNPs)/carboxylated multiwalled
      carbon nanotubes (cMWCNT)/polyaniline (PANI) layer on the surface of gold (Au)
      electrode. A polyphenol biosensor was fabricated using this enzyme electrode
      (laccase/AgNPs/cMWCNT/PANI/Au electrode) as the working electrode, Ag/AgCl as the
      reference electrode, and platinum (Pt) wire as the auxiliary electrode connected
      through a potentiostat. The biosensor showed optimal response at pH 5.5 (0.1 M
      acetate buffer) and 35 degrees C when operated at a scan rate of 50 mV s(-1).
      Linear range, response time, and detection limit were 0.1-500 MUM, 6 s, and 0.1
      MUM, respectively. The sensor was employed for the determination of total
      phenolic content in tea, alcoholic beverages, and pharmaceutical formulations.
      The enzyme electrode was used 200 times over a period of 4 months when stored at
      4 degrees C. The biosensor has an advantage over earlier enzyme sensors in that
      it has no leakage of enzyme during reuse and is unaffected by the external
      environment due to the protective PANI microenvironment.

PMID- 21855526
TI  - A methodology for simultaneous fluorogenic derivatization and boronate affinity
      enrichment of 3-nitrotyrosine-containing peptides.
AB  - We synthesized and characterized a new tagging reagent, (3R,4S)-1-(4
      (aminomethyl)phenylsulfonyl)pyrrolidine-3,4-diol (APPD), for the selective
      fluorogenic derivatization of 3-nitrotyrosine (3-NT) residues in peptides (after
      reduction to 3-aminotyrosine) and affinity enrichment. The synthetic 3-NT
      containing peptide, FSAY(3-NO(2))LER, was employed as a model for method
      validation. Furthermore, this derivatization protocol was successfully tested for
      analysis of 3-NT-containing proteins exposed to peroxynitrite in the total
      protein lysate of cultured C2C12 cells. The quantitation of 3-NT content in
      samples was achieved through either fluorescence spectrometry or boronate
      affinity chromatography with detection by specific fluorescence (excitation and
      emission wavelengths of 360 and 510 nm, respectively); the respective limits of
      detection were 95 and 68 nM (19 and 13 pmol total amount) of 3-NT. Importantly,
      the derivatized peptides show a strong retention on a synthetic boronate affinity
      column, containing sulfonamide-phenylboronic acid, under mild chromatographic
      conditions, affording a route to separate the derivatized peptides from large
      amounts (milligrams) of nonderivatized peptides and to enrich them for
      fluorescent detection and mass spectrometry (MS) identification. Tandem MS
      analysis identified chemical structures of peptide 3-NT fluorescent derivatives
      and revealed that the fluorescent derivatives undergo efficient backbone
      fragmentations, permitting sequence-specific identification of protein nitration
      at low concentrations of 3-NT in complex protein mixtures.

PMID- 21855527
TI  - Screening for lysine-specific demethylase-1 inhibitors using a label-free high
      throughput mass spectrometry assay.
AB  - Posttranslational modifications on the N terminus of histone H3 act in a
      combinatorial fashion to control epigenetic responses to extracellular stimuli.
      Lysine-specific demethylase-1 (LSD1) represents an emerging epigenetic target
      class for the discovery of novel antitumor therapies. In this study, a high
      throughput mass spectrometry (HTMS) assay was developed to measure LSD1-catalyzed
      demethylation of lysine-4 on several H3 substrates. The assay leverages RapidFire
      chromatography in line with a triple stage quadrupole detection method to measure
      multiple LSD1 substrate and product reactions from an assay well. This approach
      minimizes artifacts from fluorescence interference and eliminates the need for
      antibody specificity to methylated lysines. The assay was robust in a high
      throughput screen of a focused library consisting of more than 56,000 unique
      chemical scaffolds with a median Z' of 0.76. Validated hits from the primary
      screen were followed up by successive rounds of virtual and HTMS screening to
      mine for related structures in a parent library consisting of millions of
      compounds. The screen resulted in the rapid discovery of multiple chemical
      classes amenable to medicinal chemistry optimization. This assay was further
      developed into a generic platform capable of rapidly screening epigenetic targets
      that use the N-terminal tail of histone H3 as a substrate.

PMID- 21855528
TI  - New molecular rods--characterization of their interaction with membranes.
AB  - Molecular rods are synthetical molecules consisting of a hydrophobic backbone
      which are functionalized with varying terminal groups. Here, we report on the
      interaction of a recently described new class of molecular rods with lipid and
      biological membranes. In order to characterize this interaction, different
      fluorescently labeled rods were synthesized allowing for the application of
      fluorescence spectroscopy and microscopy based approaches. Our data show that the
      rods are incorporated into membranes with a perpendicular orientation to the
      membrane surface and enrich preferentially in liquid-disordered lipid domains.
      These characteristics underline that rods can be applied as stable membrane
      associated anchors for functionalizing membrane surfaces.

PMID- 21855529
TI  - Model membrane studies for characterization of different antibiotic activities of
      lipopeptides from Pseudomonas.
AB  - Lipopeptides (LPs) are a structurally diverse class of amphipathic natural
      products that were in the past mainly known for their surfactant properties.
      However, the recent discovery of their antimicrobial and cytotoxic bioactivities
      have fueled and renewed the interest in this compound class. Propelled by the
      antimicrobial potential of this compound class, in this study a range of six
      underinvestigated LPs from Pseudomonads were examined with respect to their
      antibiotic activities towards bacteria. The assays revealed that only the
      glycosylated lipodipeptide SB-253514, produced by Pseudomonas strain SH-C52,
      showed significant antibacterial activity. Since the bioactivity of LPs is
      commonly attributed to membrane interactions, we analyzed the molecular
      interactions between the LPs and bacteria-like lipid model membranes in more
      detail via complementary biophysical approaches. Application of the quartz
      crystal microbalance (QCM) showed that all LPs possess a high binding affinity
      towards the model membranes. Despite their similar membrane affinity, monolayer
      studies displayed different tendencies of LPs to incorporate into the membrane.
      The degree of membrane incorporation could be correlated with specific structural
      features of the investigated LPs, such as distance between the peptidic
      macrocycle and the fatty acid, but did not fully reflect their respective
      antibacterial activity. Cyclic voltammetry (CV) experiments further demonstrated
      that SB-253514 showed no membrane permeabilization effects at inhibitory
      concentrations. Collectively, these results suggests that the antibacterial
      activity of SB-253514 cannot be explained by an unspecific detergent-like
      mechanism generally proposed for amphiphilic molecules but instead appears to
      occur via a defined structural target.

PMID- 21855530
TI  - Isolation and characterization of BetaM protein encoded by ATP1B4--a unique
      member of the Na,K-ATPase beta-subunit gene family.
AB  - ATP1B4 genes represent a rare instance of the orthologous gene co-option that
      radically changed functions of encoded BetaM proteins during vertebrate
      evolution. In lower vertebrates, this protein is a beta-subunit of Na,K-ATPase
      located in the cell membrane. In placental mammals, BetaM completely lost its
      ancestral role and through acquisition of two extended Glu-rich clusters into the
      N-terminal domain gained entirely new properties as a muscle-specific protein of
      the inner nuclear membrane possessing the ability to regulate gene expression.
      Strict temporal regulation of BetaM expression, which is the highest in late
      fetal and early postnatal myocytes, indicates that it plays an essential role in
      perinatal development. Here we report the first structural characterization of
      the native eutherian BetaM protein. It should be noted that, in contrast to
      structurally related Na,K-ATPase beta-subunits, the polypeptide chain of BetaM is
      highly sensitive to endogenous proteases that greatly complicated its isolation.
      Nevertheless, using a complex of protease inhibitors, a sample of authentic BetaM
      was isolated from pig neonatal skeletal muscle by a combination of ion-exchange
      and lectin-affinity chromatography followed by SDS-PAGE. Results of the analysis
      of the BetaM tryptic digest using MALDI-TOF and ESI-MS/MS mass spectrometry have
      demonstrated that native BetaM in neonatal skeletal muscle is a product of
      alternative splice mRNA variant B and comprised of 351 amino acid residues.
      Isolated BetaM protein was also characterized by SELDI-TOF mass spectrometry
      before and after deglycosylation. This allowed us to determine that the
      carbohydrate moiety of BetaM has molecular mass 5.9kDa and consists of short high
      mannose type N-glycans. The results of direct analysis of the purified native
      eutherian BetaM protein provide first insights into structural properties
      underlying its entirely new evolutionarily acquired functions.

PMID- 21855531
TI  - Ca2+-dependent binding of calcium-binding protein 1 to presynaptic group III
      metabotropic glutamate receptors and blockage by phosphorylation of the
      receptors.
AB  - Presynaptic group III metabotropic glutamate receptors (mGluRs) and Ca(2+)
      channels are the main neuronal activity-dependent regulators of synaptic vesicle
      release, and they use common molecules in their signaling cascades. Among these,
      calmodulin (CaM) and the related EF-hand Ca(2+)-binding proteins are of
      particular importance as sensors of presynaptic Ca(2+), and a multiple of them
      are indeed utilized in the signaling of Ca(2+) channels. However, despite its
      conserved structure, CaM is the only known EF-hand Ca(2+)-binding protein for
      signaling by presynaptic group III mGluRs. Because the mGluRs and Ca(2+) channels
      reciprocally regulate each other and functionally converge on the regulation of
      synaptic vesicle release, the mGluRs would be expected to utilize more EF-hand
      Ca(2+)-binding proteins in their signaling. Here I show that calcium-binding
      protein 1 (CaBP1) bound to presynaptic group III mGluRs competitively with CaM in
      a Ca(2+)-dependent manner and that this binding was blocked by protein kinase C
      (PKC)-mediated phosphorylation of these receptors. As previously shown for CaM,
      these results indicate the importance of CaBP1 in signal cross talk at
      presynaptic group III mGluRs, which includes many molecules such as cAMP, Ca(2+),
      PKC, G protein, and Munc18-1. However, because the functional diversity of EF
      hand calcium-binding proteins is extraordinary, as exemplified by the regulation
      of Ca(2+) channels, CaBP1 would provide a distinct way by which presynaptic group
      III mGluRs fine-tune synaptic transmission.

PMID- 21855532
TI  - Glutathione-S-transferase pi 1(GSTP1) gene silencing in prostate cancer cells is
      reversed by the histone deacetylase inhibitor depsipeptide.
AB  - Gene silencing by epigenetic mechanisms is frequent in prostate cancer (PCA). The
      link between DNA hypermethylation and histone modifications is not completely
      understood. We chose the GSTP1 gene which is silenced by hypermethylation to
      analyze the effect of the histone deacetylase inhibitor depsipeptide on DNA
      methylation and histone modifications at the GSTP1 promoter site. Prostate cell
      lines (PC-3, LNCaP, and BPH-1) were treated with depsipeptide; apoptosis (FACS
      analysis), GSTP1 mRNA levels (quantitative real-time PCR), DNA hypermethylation
      (methylation-specific PCR), and histone modifications (chromatin
      immunoprecipitation) were studied. Depsipeptide induced apoptosis in PCA cells,
      but not a cell cycle arrest. Depispeptide reversed DNA hypermethylation and
      repressive histone modifications (reduction of H3K9me2/3 and H3K27me2/3; increase
      of H3K18Ac), thereby inducing GSTP1 mRNA re-expression. Successful therapy
      requires both, DNA demethylation and activating histone modifications, to induce
      complete gene expression of epigenetically silenced genes and depsipeptide
      fulfils both criteria.

PMID- 21855533
TI  - In vitro and in vivo modulation of ABCG2 by functionalized aurones and
      structurally related analogs.
AB  - Over-expression of ABCG2 is linked to multidrug resistance in cancer
      chemotherapy. We have previously shown that functionalized aurones effectively
      reduced the efflux of pheophorbide A (an ABCG2 substrate) from ABCG2 over
      expressing MDA-MB-231/R ("R") cells. In the present report, we investigated the
      functional relevance of this observation and the mechanisms by which it occurs.
      Aurones and related analogs were investigated for re-sensitization of R cells to
      mitoxantrone (MX, a chemotherapeutic substrate of ABCG2) in cell-based assays,
      accumulation of intracellular MX by cell cytometry, interaction with ABCG2 by
      biochemical assays and in vivo efficacy in MX resistant nude mice xenografts. We
      found that methoxylated aurones interacted directly with ABCG2 to inhibit efflux
      activity, possibly by competing for occupancy of one of the substrate binding
      sites on ABCG2. The present evidence suggests that they are not transported by
      ABCG2 although they stimulate ABCG2-ATPase activity. Alteration of ABCG2 protein
      expression was also discounted. One member was found to re-sensitize R cells to
      MX in both in vitro and in vivo settings. Our study identified methoxylated
      aurones as promising compounds associated with low toxicities and potent
      modulatory effects on the ABCG2 efflux protein. Thus, they warrant further
      scrutiny as lead templates for development as reversal agents of multidrug
      resistance.

PMID- 21855534
TI  - Using spin-label electron paramagnetic resonance (EPR) to discriminate and
      characterize the cholesterol bilayer domain.
AB  - Electron paramagnetic resonance (EPR) spin-labeling methods make it possible not
      only to discriminate the cholesterol bilayer domain (CBD) but also to obtain
      information about the organization and dynamics of cholesterol molecules in the
      CBD. The abilities of spin-label EPR were demonstrated for Chol/POPC
      (cholesterol/1-palmitoyl-2-oleoylphosphatidylcholine) membranes, with a Chol/POPC
      mixing ratio that changed from 0 to 3. Using the saturation-recovery (SR) EPR
      approach with cholesterol analogue spin labels, ASL and CSL, and oxygen or NiEDDA
      relaxation agents, it was confirmed that the CBD was present in all membrane
      suspensions when the mixing ratio exceeded the cholesterol solubility threshold
      (CST). Conventional EPR spectra of ASL and CSL in the CBD were similar to those
      in the surrounding POPC bilayer (which is saturated with cholesterol), indicating
      that in both domains, cholesterol exists in the lipid-bilayer-like structures.
      The behavior of ASL and CSL (and, thus, the behavior of cholesterol molecules) in
      the CBD was compared with that in the surrounding POPC-cholesterol domain (PCD).
      In the CBD, ASL and CSL molecules are better ordered than in the surrounding PCD.
      This difference is small and can be compared to that induced in the surrounding
      domain by an ~10 degrees C decrease in temperature. Thus, cholesterol molecules
      are unexpectedly dynamic in the CBD, which should enhance their interaction with
      the surrounding domain. The polarity of the water/membrane interface of the CBD
      is significantly greater than that of the surrounding PCD, which significantly
      enhances penetration of the water-soluble relaxation agent, NiEDDA, into that
      region. Hydrophobicity measured in the centers of both domains is similar. The
      oxygen transport parameter (oxygen diffusion-concentration product) measured in
      the center of the CBD is about ten times smaller than that measured in the center
      of the surrounding domain. Thus, the CBD can form a significant barrier to oxygen
      transport. The results presented here point out similarities between the
      organization and dynamics of cholesterol molecules in the CBD and in the
      surrounding PCD, as well as significant differences between CBDs and cholesterol
      crystals.

PMID- 21855535
TI  - Heteroscedasticity and homoscedasticity, and precision profiles in clinical
      laboratory sciences.

PMID- 21855536
TI  - The ratio of serum leptin to adiponectin provides adjunctive information to the
      risk of metabolic syndrome beyond the homeostasis model assessment insulin
      resistance: the Korean Genomic Rural Cohort Study.
AB  - BACKGROUND: Leptin and adiponectin are adipokines, shown to have opposing
      functions for fat metabolism and development of metabolic syndrome. We determined
      if the ratio of serum leptin to adiponectin (L/A ratio) adjunctively contributes
      to the risk of metabolic syndrome beyond the homeostasis model assessment of
      insulin resistance (HOMA-IR). METHODS: This study included 1532 men and 1856
      women, aged 40-70 y assessed in the Korean Genomic Rural Cohort Study from 2005
      to 2008. The serum concentrations of adiponectin and leptin were measured by
      radioimmunoassay. Area under the receiver operating characteristic curve (AUROC)
      analyses were used to describe the ability of L/A ratio and HOMA-IR to
      differentiate between subjects with and without metabolic syndrome. RESULTS:
      There were no significant differences in the ability of L/A ratio and HOMA-IR to
      predict metabolic syndrome (AUROC of L/A ratio vs. HOMA-IR, 0.771 vs. 0.774,
      p=0.8006 for men; 0.677 vs. 0.691, p=0.3088 for women). There was a significant
      adjunctive contribution by the L/A ratio, beyond that of HOMA-IR, to the risk of
      metabolic syndrome in men (p<0.0001 with 0.028 increased AUROC) and women
      (p=0.025 with 0.017 increased AUROC). CONCLUSIONS: The L/A ratio provides
      significant adjunctive information to the risk of metabolic syndrome beyond HOMA
      IR alone. The L/A ratio could be a good surrogate marker to assess metabolic
      syndrome.

PMID- 21855537
TI  - Oxysterols in bile acid metabolism.
AB  - Increasing body of evidence is available indicating that oxysterols are more much
      than intermediates of metabolic pathways. Oxysterols play a role in the
      regulation of cholesterol synthesis, transport and efflux. A scavenger effect of
      cholesterol 27-hydroxylase on elevated serum cholesterol levels is well
      demonstrated. Bile acid synthesis occurs through two main pathways, the classic
      and the alternative ones. Since plasma concentrations of 27-hydroxycholesterol
      were clearly shown to reflect its production rate the alternative pathway of bile
      acid synthesis can be easily explored. Conversely this was not true for 7alpha
      hydroxycholesterol and also the direct evaluation of the classic pathway by
      kinetic studies is more difficult since the rate of plasma appearance during
      continuous infusion of deuterated isotopomers may not exactly measure its
      production rate. Hepatic cholesterol 7alpha-hydroxylase activity is absent during
      fetal life in humans and upregulates after birth. Both the classic and
      alternative pathways become mature after the age of 4 years. It has been clearly
      demonstrated that in patients with liver disease the classic pathway is impaired
      while the alternative one is preserved. Conversely, in obese patients,
      preliminary data suggest an increase of the production rate of 27
      hydroxycholesterol, a possible mechanism to counteract the increase of
      atherosclerotic risk.

PMID- 21855538
TI  - Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis
      without significant hepatic inflammation.
AB  - Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and
      the metabolic syndrome. It encompasses a clinico-pathologic spectrum of
      conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH).
      The latter develops upon pro-inflammatory cell infiltration and is widely
      considered as the first relevant pathophysiological step in NAFLD-progression.
      The chemokine monocyte chemoattractant protein 1 (MCP-1) plays an important role
      in the progression of hepatic inflammation and fibrosis, and both increased
      hepatic expression and circulating serum levels have been described in NASH.
      Here, we aimed to investigate MCP-1 expression in simple hepatic steatosis. Upon
      feeding a high-fat diet mice developed hepatic steatosis in the absence of
      significant hepatic inflammation, but elevated hepatic MCP-1 expression compared
      to control mice fed a standard chow. Interestingly, high-fat diet fed mice had
      significantly higher MCP-1 serum levels, and MCP-1 mRNA expression was
      significantly increased in visceral adipose tissue. Furthermore, MCP-1 serum
      levels were also elevated in patients with ultrasound-diagnosed NAFLD and
      correlated with the body-mass index and fasting glucose. In conclusion, our data
      indicate both the liver and adipose tissue as cellular sources of elevated
      circulating MCP-1 levels already in the early phase of hepatic steatosis. Since
      MCP-1 derived from visceral adipose tissue reaches the liver via portal
      circulation at high concentrations it may significantly contribute to the
      progression of simple steatosis to NASH.

PMID- 21855539
TI  - Chronic alcohol consumption induces cardiac remodeling in mice from Th1 or Th2
      background.
AB  - AIMS: The effects of T helper (Th) cells on alcoholic cardiomyopathy have not
      been extensively investigated. Strain of mice with Th1 or Th2 immunological
      background were utilized in this study in order to explore the role of Th1/Th2 in
      chronic alcohol-induced cardiac fibrosis. METHODS AND RESULTS: C57BL/6 WT or
      Balb/c mice were treated with alcohol for 90 days. Then cardiac structure and
      function were analyzed via echocardiography. Spleen CD4+CD25+Foxp3+ Tregs were
      determined by flow cytometry. The hearts were stained using haematoxylin and
      eosin (HE) and Masson's trichome. Myocardial ultrastructure was observed by
      electron microscopy. Expression of T-bet, GATA-3, IL-4 and IFN-gamma were
      determined by real-time RT-PCR. The heart was dilated significantly in the
      C57BL/6 WT+alcohol group and Balb/c+alcohol group compared with the controls.
      CD4+CD25+Foxp3+ Tregs were not statistically different. Masson's trichome
      staining revealed that fibrosis was more pronounced in the alcohol treated groups
      than the controls. Fibrosis was more evident in the Balb/c+alcohol group compared
      to the C57BL/6 WT+alcohol group. Alcohol consumption caused a decrease in the Th1
      polarization and an increase in the Th2 response. CONCLUSIONS: Chronic alcohol
      consumption induced a Th2 response within the Th1/Th2 balance. Th2 response is
      one of the underlying mechanism involved in alcohol-induced cardiac fibrosis.

PMID- 21855540
TI  - Demonstrating collagen tendon fibril segments involvement in intrinsic tendon
      repair.
AB  - Severed tendons can undergo regenerative healing, intrinsic tendon repair.
      Fibrillogenesis of chick tendon involves "collagen fibril segments" (CFS), which
      are the building blocks of collagen fibers that make up tendon fascicles. The CFS
      are 10.5 micron in length, composed of tropocollagen monomers arranged in
      parallel arrays. Rather than incorporating single tropocollagen molecules into
      growing collagen fibers, incorporating large CFS units is the mechanism for
      generating collagen fibers. Is intrinsic tendon repair through the
      reestablishment of tendon embryogenesis? Gentamicin treated 10-day-old chick
      embryo tendons released CFS were fluorescently tagged with Rhodamine (Rh). Organ
      cultured severed 14-day-old embryo tendon explants received Rh tagged CFS. At day
      4 auto fluorescent tagged CFS were identified at the severed tendon ends by
      fluorescent microscopy. Accumulation of fluorescent tagged CFS was exclusively
      localized to the severed ends of tendon explants. Parallels between collagen
      fiber growth during embryonic fibrillogenesis and tendon repair reveal CFS
      incorporation is responsible for collagen fibers growth. CFS incorporation into
      frayed collagen fibers from severed tendons is the proposed mechanism for
      intrinsic tendon repair, which is an example of regenerative repair.

PMID- 21855541
TI  - N-cadherin mediates angiogenesis by regulating monocyte chemoattractant protein-1
      expression via PI3K/Akt signaling in prostate cancer cells.
AB  - Over the past decade, evidence continues to mount showing that N-cadherin is a
      critical protein in cancer progression and metastasis. In the present study, we
      evaluated the expression of N-cadherin in human prostate cancer tissue specimens
      and cell lines. Enhanced expression of N-cadherin was observed in both the
      malignant and bone-metastasized prostate tissue specimens compared to the healthy
      prostate tissues. Consistent with the tissue array data, N-cadherin was highly
      expressed in PC3, but not in Du145 and LNCaP human prostate cell lines. Based on
      cell to cell binding assay, we found that N-cadherin expression facilitates
      homotypic interaction between human prostate cancer cells and human microvascular
      endothelial cells (HMEC). Human angiogenesis antibody array and in vitro
      angiogenesis assay showed that siRNA-mediated knockdown of N-cadherin reduced the
      secretion of monocyte chemoattractant protein-1 (MCP-1), which played a potential
      role in stimulating capillary network formation of HMEC. Additionally, culture
      supernatant of Du145 cells transfected with full-length N-cadherin expressing
      plasmid showed increased MCP-1 expression and chemoattractant ability compared to
      normal Du145 cells. Further, we noticed that blocking PI3K activity inhibited N
      cadherin mediated MCP-1 expression. Our data demonstrated that N-cadherin in
      prostate cancer cell mediates cell-cell adhesion and regulates MCP-1 expression
      via the PI3K/Akt signaling pathway.

PMID- 21855543
TI  - Endothelial mesenchymal transformation mediated by IL-1beta-induced FGF-2 in
      corneal endothelial cells.
AB  - This review describes the molecular mechanism of endothelial mesenchymal
      transformation (EMT) mediated by fibroblast growth factor-2 (FGF-2) in corneal
      endothelial cells (CECs). Corneal fibrosis is not frequently observed in corneal
      endothelium/Descemet's membrane complex; but when this pathologic tissue is
      produced, it causes a loss of vision by physically blocking light transmittance.
      Herein, we will address the cellular activities of FGF-2 and its signaling
      pathways during the EMT process. Furthermore, we will discuss the role of
      inflammation on FGF-2-mediated EMT. Interleukin-1beta (IL-1beta) greatly
      upregulates FGF-2 production in CECs, thus leading to FGF-2-mediated EMT; the
      whole spectrum of the injury-mediated inflammation (IL-1beta pathway) and the
      subsequent EMT process (FGF-2 pathway) will be briefly discussed. Intervention in
      the two pathways will provide the means to block EMT before inflammation causes
      an irreversible change, such as the production of retrocorneal fibrous membrane
      observed in human eyes.

PMID- 21855544
TI  - Sobemovirus RNA linked to VPg over a threonine residue.
AB  - Positive sense ssRNA virus genomes from several genera have a viral protein
      genome-linked (VPg) attached over a phosphodiester bond to the 5' end of the
      genome. The VPgs of Southern bean mosaic virus (SBMV) and Ryegrass mottle virus
      (RGMoV) were purified from virions and analyzed by mass spectrometry. SBMV VPg
      was determined to be linked to RNA through a threonine residue at position one,
      whereas RGMoV VPg was linked to RNA through a serine also at the first position.
      In addition, we identified the termini of the corresponding VPgs and discovered
      three and seven phosphorylation sites in SBMV and RGMoV VPgs, respectively. This
      is the first report on the use of threonine for linking RNA to VPg.

PMID- 21855542
TI  - Molecular bases of corneal endothelial dystrophies.
AB  - The phrase "corneal endothelial dystrophies" embraces a group of bilateral
      corneal conditions that are characterized by a non-inflammatory and progressive
      degradation of corneal endothelium. Corneal endothelial cells exhibit a high pump
      site density and, along with barrier function, are responsible for maintaining
      the cornea in its natural state of relative dehydration. Gradual loss of
      endothelial cells leads to an insufficient water outflow, resulting in corneal
      edema and loss of vision. Since the pathologic mechanisms remain largely unknown,
      the only current treatment option is surgical transplantation when vision is
      severely impaired. In the past decade, important steps have been taken to
      understand how endothelial degeneration progresses on the molecular level.
      Studies of affected multigenerational families and sporadic cases identified
      genes and chromosomal loci, and revealed either Mendelian or complex disorder
      inheritance patterns. Mutations have been detected in genes that carry important
      structural, metabolic, cytoprotective, and regulatory functions in corneal
      endothelium. In addition to genetic predisposition, environmental factors like
      oxidative stress were found to be involved in the pathogenesis of
      endotheliopathies. This review summarizes and crosslinks the recent progress on
      deciphering the molecular bases of corneal endothelial dystrophies.

PMID- 21855545
TI  - Xenoestrogens elicit a modulation of endocannabinoid system and estrogen
      receptors in 4NP treated goldfish, Carassius auratus.
AB  - Based on pharmacological, behavioral and neuroanatomical studies, the
      endocannabinoids appear to be pivotal in some important neuroendocrine
      regulations of both vertebrates and invertebrates. Interestingly, a well
      developed endocannabinoid system was recently demonstrated by us in different
      bonyfish brain areas which control reproduction, energy balance and stress. Fish
      in particular are very sensitive to different types of stressors which can
      heavily affect their reproductive activity and negatively reverberate on
      aquaculture. Since recent new data have been reported on endocrine disruptors
      (EDs) impact on zebrafish receptor CB1 expression, in the present research we
      have investigated the response of the endocannabinoid system to acute treatment
      with an environmental stressor such as the xenoestrogen nonylphenol (4NP) in the
      brain and peripheral tissues of the goldfish Carassius auratus. First of all the
      estrogenic effects induced by 4NP were demonstrated by a dose-dependent increase
      of plasma levels and gene expression of the biomarker vitellogenin, then changes
      in cannabinoid receptors and anandamide degradative enzyme, the fatty acid amide
      hydrolase (FAAH), were analysed by means of Real Time PCR. As the exposure to EDs
      may lead to an activation of estrogen receptors and affects the Aromatase (AROB)
      transcription, changes in mRNA levels for ER subtypes and AROB were also
      evaluated. Our results confirm in goldfish the effect of 4NP on ERalpha and
      ERbeta1 receptors and point out a different sensitivity of CB1 and CB2 for this
      compound, suggesting distinct roles of these cannabinoid receptors in some
      adaptive processes to contrast stress induced by xenoestrogen exposure.

PMID- 21855546
TI  - The prolactin response to an acute stressor in relation to parental care and
      corticosterone in a short-lived bird, the Eurasian hoopoe.
AB  - Prolactin plays an important role in mediating parental care in birds, but little
      is known about changes in prolactin levels when animals disrupt their
      reproductive behaviour during emergency life-history stages. We investigated the
      variation of prolactin levels with breeding stage, sex, body condition and as a
      response to a standardized acute stressor in a small short-lived bird, the
      Eurasian hoopoe Upupa epops under natural field conditions. We found higher
      baseline levels of prolactin in females during the brooding phase than in their
      mates which feed them and their chicks at this stage. Moreover, this is the first
      report of a differential prolactin stress-response between sexes with contrasting
      parental care within a breeding phase. Capture, handling and restraint induced a
      clear decrease of prolactin levels which was less pronounced in females at the
      very early stage of brooding compared to females in later stages. In contrast,
      the prolactin stress response in males remained nearly constant over the breeding
      stages and was stronger than in females. Baseline levels of prolactin, but not
      handling-induced levels, were positively correlated with body condition. We found
      a weak relationship between the decrease in prolactin due to acute handling
      stress and handling-induced levels of corticosterone. Taken together, both
      baseline and stress response levels of prolactin were related to the amount of
      parental care, although we found no relationship with reproductive success. It
      appears that the response to an acute stressor in prolactin levels is finely
      tuned to parental duties and investment. Hence, prolactin appears to be involved
      in mediating the trade-off between current reproduction versus self-maintenance
      and future reproduction.

PMID- 21855547
TI  - Mortality of coho salmon (Oncorhynchus kisutch) associated with burdens of
      multiple parasite species.
AB  - Multiple analytical techniques were used to evaluate the impact of multiple
      parasite species on the mortality of threatened juvenile coho salmon
      (Oncorhynchus kisutch) from the West Fork Smith River, Oregon, USA. We also
      proposed a novel parsimonious mathematical representation of macroparasite
      distribution, congestion rate, which (i) is easier to use than traditional
      models, and (ii) is based on Malthusian parameters rather than probability
      theory. Heavy infections of Myxobolus insidiosus (Myxozoa) and metacercariae of
      Nanophyetus salmincola and Apophallus sp. occurred in parr (subyearlings) from
      the lower mainstem of this river collected in 2007 and 2008. Smolts (yearlings)
      collected in 2007-2010 always harboured fewer Apophallus sp. with host mortality
      recognised as a function of intensity for this parasite. Mean intensity of
      Apophallus sp. in lower mainstem parr was 753 per fish in 2007 and 856 per fish
      in 2008, while parr from the tributaries had a mean of only 37 or 13 parasites
      per fish, respectively. Mean intensity of this parasite in smolts ranged between
      47 and 251 parasites per fish. Over-dispersion (variance to mean ratios) of
      Apophallus sp. was always lower in smolts compared with all parr combined or
      lower mainstem parr. Retrospective analysis based on smolt data using both the
      traditional negative binomial truncation technique and our proposed congestion
      rate model showed identical results. The estimated threshold level for mortality
      involving Apophallus sp. was at 400-500 parasites per fish using both analytical
      methods. Unique to this study, we documented the actual existence of these heavy
      infections prior to the predicted mortality. Most of the lower mainstem parr
      (approximately 75%) had infections above this level. Heavy infections of
      Apophallus sp. metacercariae may be an important contributing factor to the high
      over-wintering mortality previously reported for these fish that grow and develop
      in this section of the river. Analyses using the same methods for M.insidiosus
      and N. salmincola generally pointed to minimal parasite-associated mortality.

PMID- 21855549
TI  - Protein expression following heat shock in the nervous system of Locusta
      migratoria.
AB  - There is a thermal range for the operation of neural circuits beyond which
      nervous system function is compromised. Locusta migratoria is native to the
      semiarid regions of the world and provides an excellent model for studying neural
      phenomena. In this organism previous exposure to sublethal high temperatures
      (heat shock, HS) can protect neuronal function against future hyperthermia but,
      unlike many organisms, the profound physiological adaptations are not accompanied
      by a robust increase of Hsp70 transcript or protein in the nervous system. We
      compared Hsp70 increase following HS in the tissues of isolated and gregarious
      locusts to investigate the effect of population density. We also localized Hsp70
      in the metathoracic ganglion (MTG) of gregarious locusts to determine if HS
      affects Hsp70 in specific cell types that could be masked in whole ganglion
      assays. Our study indicated no evidence of a consistent change in Hsp70 level in
      the MTG of isolated locusts following HS. Also, Hsp70 was mainly localized in
      perineurium, neural membranes and glia and prior HS had no effect on its density
      or distribution. Finally, we applied 2-D gels to study the proteomic profile of
      MTG in gregarious locusts following HS; although these experiments showed some
      changes in the level of ATP-synthase beta isoforms, the overall amount of this
      protein was found unchanged following HS. We conclude that the constitutive level
      of Hsps in the tissues of locusts is high. Also the thermoprotective effect of HS
      on the nervous system might be mediated by post-translational modifications or
      protein trafficking.

PMID- 21855548
TI  - Combined Fc-protein- and Fc-glyco-engineering of scFv-Fc fusion proteins
      synergistically enhances CD16a binding but does not further enhance NK-cell
      mediated ADCC.
AB  - Protein- or glyco-engineering of antibody molecules can be used to enhance Fc
      mediated effector functions. ScFv-Fc fusion proteins (scFv-Fc) represent
      interesting antibody derivatives due to their relatively simple design and
      increased tissue penetration. Here, the impact of protein- and glyco-engineering
      on ADCC potency of a panel of human IgG1-based scFv-Fc was tested. Three matched
      sets of scFv-Fc variants targeting CD7, CD20 or HLA class II and optimized for
      CD16a binding by mutagenesis, lack of core-fucose, or their combination, were
      generated and functionally tested in comparison to the corresponding wild type
      scFv-Fc. Antigen binding activity was not compromised by altered glycosylation or
      Fc mutagenesis, whereas Fc binding to CD16a was significantly enhanced in the
      order: non-core fucosylated/Fc-mutated double-engineered?Fc-mutated>=non-core
      fucosylated>wild-type IgG1-Fc. All engineered variants triggered potent ADCC with
      up to 100-fold reduced EC50 values compared to non-engineered variants.
      Interestingly, double-engineered variants were similarly effective in triggering
      ADCC compared to single-engineered variants irrespective of their 1 log greater
      CD16a binding affinity. Thus, these data demonstrate that protein- and glyco
      engineering enhances NK-cell mediated ADCC of scFv-Fc similarly and show that
      enhancing CD16a affinity beyond a certain threshold does not result in a further
      increase of NK-cell mediated ADCC.

PMID- 21855550
TI  - Coping with an unpredictable and stressful environment: the life history and
      metabolic response to variable food and host availability in a polyphagous
      tephritid fly.
AB  - The way energy resources are used under variable environmental conditions lies at
      the heart of our understanding of resource management and opportunism in many
      organisms. Here we sought to determine how a time-limited, synovigenic and
      polyphagous insect with a high reproductive-potential (Anastrephaludens), copes
      behaviourally and metabolically with environmental unpredictability represented
      by constant and variable regimes of host availability and variation in food
      quality. We hypothesized that an adaptive response to a windfall of nutritious
      food would be the rapid accumulation of energy metabolites (whole body lipids,
      glycogen and proteins) in the female. We also studied patterns of oogenesis as an
      indicator of egg-reabsorption under stressful environmental conditions. As
      predicted, patterns of energy metabolites were mainly driven by the quality and
      temporal pattern of food availability. In contrast, patterns of host availability
      had a lower impact upon metabolites. When given constant access to high quality
      nutrients, after an initial increase early in life, whole body lipids and
      glycogen were regulated downward to a steady-state level and somatic protein
      levels did not vary. In contrast, when food uncertainty was introduced, whole
      body lipid, glycogen and protein oscillated sharply with peaks associated with
      pulses of high-quality food. Production of eggs was highest when offered
      continuous access to hosts and high quality food. Importantly, females fully
      recovered their reproductive capacity when fruit became available following a
      period of host deprivation. With no evidence of egg resorption and high levels of
      egg dumping, it appears that egg dumping may favour the continuous production of
      eggs such that the female's reproductive tissues are ready to respond to rapid
      changes in the availability of hosts. Our results exemplify the capacity of
      insects to maximize reproduction under variable and stressful environmental
      conditions.

PMID- 21855552
TI  - Contrasting effects of moderate vagal stimulation on heart rate and carotid sinus
      baroreflex-mediated sympathetic arterial pressure regulation in rats.
AB  - AIMS: To examine whether moderate efferent vagal nerve stimulation (VNS)
      attenuates the carotid sinus baroreflex-mediated arterial pressure (AP)
      regulation via its antagonism to the sympathetic system. MAIN METHODS: Carotid
      sinus baroreceptor regions were isolated from the systemic circulation in eight
      anesthetized and vagotomized rats. A staircase-wise input was imposed on carotid
      sinus pressure (CSP) with or without efferent VNS (20Hz, 2ms, 1-4V), while the
      responses in AP, heart rate (HR), and splanchnic sympathetic nerve activity (SNA)
      were measured. KEY FINDINGS: A multiple linear regression analysis indicated that
      VNS decreased the minimum HR in the CSP-HR relationship by 58.2+/-4.9 beats/min
      (P<0.01) from its reference value of 387.0+/-5.8 beats/min. Although VNS
      significantly decreased an intercept of the SNA-AP relationship, it did not
      affect parameters of the CSP-AP relationship or the CSP-SNA relationship
      significantly. The operating-point AP of the baroreflex was decreased by 2.8+/
      1.0mmHg (P<0.01) during VNS, which was less than 3% of the reference value of
      117.7+/-1.2mmHg. SIGNIFICANCE: VNS, at an intensity of decreasing HR by
      approximately 13%, does not acutely attenuate the baroreflex-mediated sympathetic
      AP regulation.

PMID- 21855551
TI  - The role of MukE in assembling a functional MukBEF complex.
AB  - The MukB-MukE-MukF protein complex is essential for chromosome condensation and
      segregation in Escherichia coli. The central component of this complex, the MukB
      protein, is related functionally and structurally to the ubiquitous SMC
      (structural maintenance of chromosomes) proteins. In a manner similar to SMC,
      MukB requires the association of two accessory proteins (MukE and MukF) for its
      function. MukF is a constitutive dimer that bridges the interaction between MukB
      and MukE. While MukB can condense DNA on its own, it requires MukF and MukE to
      ensure proper chromosome segregation. Here, we present a novel structure of the
      E. coli MukE-MukF complex, in which the intricate crystal packing interactions
      reveal an alternative MukE dimerization interface spanning both N- and C-terminal
      winged-helix domains of the protein. The structure also unveils additional cross
      linking interactions between adjacent MukE-MukF complexes mediated by MukE. A
      variant of MukE encompassing point mutations on one of these surfaces does not
      affect assembly of the MukB-MukE-MukF complex and yet cannot restore the
      temperature sensitivity of the mukE?kan strain, suggesting that this surface may
      mediate critical protein-protein interactions between MukB-MukE-MukF complexes.
      Since the dimerization interface of MukE overlaps with the region of the protein
      that interacts with MukB in the MukB-MukE-MukF complex, we suggest that competing
      MukB-MukE and MukE-MukE interactions may regulate the formation of higher-order
      structures of bacterial condensin.

PMID- 21855553
TI  - Rat liver uncoupling protein 2: changes induced by a fructose-rich diet.
AB  - AIM: To evaluate the role of uncoupling protein 2 (UCP2) and peroxisome
      proliferator-activated receptors (PPARs) in the response of liver to
      glycoxidative stress triggered by administration of a fructose-rich diet (FRD).
      MAIN METHODS: We assessed blood glucose in the fasting state and after a glucose
      load (glucose-oxidase method), serum triglyceride (enzymatic measurement),
      insulin (radioimmunoassay), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels (colorimetric kits) in control and FRD animals. In
      liver, we measured UCP2, PPARalpha, PPARdelta and PPARgamma gene (real-time PCR)
      and protein (Western blot) expression, fatty acid synthase (FAS) and glycerol-3
      phosphate acyltransferase (GPAT) gene expression, as well as triglyceride
      content. KEY FINDINGS: Blood glucose, serum insulin and triglyceride levels,
      homeostasis model assessment of insulin resistance (HOMA-IR) indexes and impaired
      glucose tolerance were higher in FRD rats. Whereas UCP2 and PPARdelta gene and
      protein expression increased in these animals; PPARgamma levels were lower and
      those of PPARalpha remained unchanged. FRD also increased the mRNA expression of
      PPARdelta target genes FAS and GPAT. SIGNIFICANCE: Our results suggest that a)
      the increased UCP2 gene and protein expression measured in FRD rats could be part
      of a compensatory mechanism to reduce reactive oxygen species production induced
      by the fructose overload, and b) PPARs expression participates actively in the
      regulation of UCP2 expression, and under the metabolic condition tested,
      PPARdelta played a key role. This knowledge would help to better understand the
      mechanisms involved in liver adaptation to fructose-induced glycoxidative stress,
      and to develop appropriate prevention strategies in obesity and type 2 diabetes.

PMID- 21855554
TI  - The contribution of prostaglandins versus prostacyclin in ventricular remodeling
      during heart failure.
AB  - Although the role of Cox-2 in the heart's response to physiologic stress remains
      controversial (i.e. expression in myocytes versus other resident myocardial
      cells) the ever expanding role of prostanoids in multiple models of heart failure
      cannot be denied. Due to the fact that prostanoids are metabolized rather quickly
      (half life of seconds to minutes) it is believed these signaling mediators act in
      a paracrine fashion at the site of production. Evidence to date is quite
      convincing that these bioactive lipid derivatives are involved in physiologic
      homeostatic regulation as well as beneficial and maladaptive ventricular
      remodeling in heart failure. Thus, this review will assess the direct
      contribution of each PG on remodeling in the left ventricle (e.g. hypertrophy,
      functional effects, and fibrosis).

PMID- 21855555
TI  - On the mechanism of anti-hyperthermic effects of LY379268 and LY487379, group II
      mGlu receptors activators, in the stress-induced hyperthermia in singly housed
      mice.
AB  - Earlier studies have demonstrated that the agonists of the mGlu(2/3) receptors
      produced anxiolytic actions after peripheral administration. However, the
      mechanism of their action is still not clear. Therefore the aim of the present
      study was to specify the role of the GABAergic and serotonergic system in the
      mechanism of the anxiolytic activity of group II mGlu receptor activators by
      using the stress induced hyperthermia test (SIH) in singly housed mice. We used
      an orthosteric mGlu(2/3) receptor agonist, LY379268, which induced anti
      hyperthermic efficacy in the doses of 1-5mg/kg (73% of inhibition after a highest
      dose). The effect of the second ligand used, a mGlu(2) receptor positive
      modulator (PAM), LY487379, was observed in a dose range of 0.5-5mg/kg and reached
      53% of the inhibition. The blockade of GABAergic system by GABA(A) receptor
      antagonist flumazenil (10mg/kg) or GABA(B) receptor antagonist CGP55845
      (10mg/kg), and the blockade of serotonergic system by 5-HT(1A) receptor
      antagonist WAY100635 (0.1 and 1mg/kg) or 5-HT(2A/2C) receptor antagonist
      ritanserin (0.5mg/kg) had no influence on the anti-hyperthermic effect induced by
      effective dose of LY379268. However, the action of the effective dose of LY487379
      was enhanced when co-administered with flumazenil, WAY100635 (0.1mg/kg) and
      ritanserin. Similar results were observed for the subeffective dose of LY379268
      (0.5mg/kg). WAY100635 in a dose of 1mg/kg did not induce any enhancing effect on
      the activity of compounds. Therefore, it seems that the antagonism towards
      GABA(A) receptors, presynaptic 5-HT(1A) and postsynaptic 5-HT(2A/2C) receptors is
      responsible for the phenomenon. This article is part of a Special Issue entitled
      'Anxiety and Depression'.

PMID- 21855556
TI  - A contribution to the study of environmental dependency phenomena: the social
      hypothesis.
AB  - Environmental dependency phenomena refer to the symptoms initially described by
      Lhermitte (1983, 1984) under the terms of "utilization behavior" and "imitation
      behavior". These clinical signs are linked to essential notions such as free-will
      and human autonomy, and seem to be specific of the frontal pathology.
      Surprisingly, few studies have addressed these symptoms and inconsistent
      definitions are available. To investigate the theoretical and clinical
      definitions of environmental dependency phenomena, three groups of neurological
      patients (n=60) with frontal, subcortical, and posterior brain lesions were
      compared. Clinically, our findings help to rehabilitate the definitions of
      Lhermitte (1983, 1984) and challenge the classical interpretation in terms of an
      executive control deficit. The frontal specificity of the disorders and the lack
      of relation between executive/behavioral deficits were supported. The right
      orbitofrontal cortex seems particularly involved in environmental dependency.
      These results offer some evidences for differentiate two historical concepts of
      neuropsychology, namely the "frontal" and "dysexecutive" syndromes. A new
      interpretation of environmental dependency phenomena is provided which could be
      helpful to orient the neuropsychology of frontal syndrome.

PMID- 21855557
TI  - Role of 17beta-estradiol and testosterone in apoptosis.
AB  - 17beta-Estradiol (E2) and Testosterone (T) exert actions in most animal tissues,
      in addition to the reproductive system. Thus, both sex steroid hormones affect
      growth and different cell functions in several organs. Accordingly, the nuclear
      estrogen (ER) and androgen (AR) receptors are ubiquitously expressed. Moreover,
      ER and AR may have non-classical intracellular localizations, e.g. plasma
      membrane, mitochondria and endoplasmic reticulum, raising additional complexity
      to the functional roles of E2 and T. In addition to the modulation of gene
      transcription by direct interaction with their cognate nuclear receptors, the
      steroids can rapidly activate signaling pathways by a non-genomic mechanism
      mediated by receptors identical to or different from known steroid receptors.
      Among various functions, E2 and T can regulate apoptosis through those pathways.
      In mitochondria, the presence of ER and AR and actions of estrogen and androgen
      have been shown, in keeping with the organelle being a control point of
      apoptosis. The most recurrent action for each steroid hormone is the protection
      of mitochondria against different insults, resulting in antiapoptosis. This
      review summarizes the molecular basis of the modulation of programmed cell death
      by E2 and T in several tissues.

PMID- 21855558
TI  - Glucocorticoids exert context-dependent effects on cells of the joint in vitro.
AB  - INTRODUCTION: Glucocorticoids are known to attenuate bone formation in vivo
      leading to decreased bone volume and increased risk of fractures, whereas effects
      on the joint tissue are less characterized. However, glucocorticoids appear to
      have a reducing effect on inflammation and pain in osteoarthritis. This study
      aimed at characterizing the effect of glucocorticoids on chondrocytes,
      osteoclasts, and osteoblasts. EXPERIMENTAL: We used four model systems to
      investigate how glucocorticoids affect the cells of the joint; two intact tissues
      (femoral head- and cartilage-explants), and two separate cell cultures of
      osteoblasts (2T3-pre-osteoblasts) and osteoclasts (CD14(+)-monocytes). The model
      systems were cultured in the presence of two glucocorticoids; prednisolone or
      dexamethasone. To induce anabolic and catabolic conditions, cultures were
      activated by insulin-like growth factor I/bone morphogenetic protein 2 and
      oncostatin M/tumor necrosis factor-alpha, respectively. Histology and markers of
      bone- and cartilage-turnover were used to evaluate effects of glucocorticoid
      treatment. RESULTS: Prednisolone treatment decreased collagen type-II degradation
      in immature cartilage, whereas glucocorticoids did not affect collagen type-II in
      mature cartilage. Glucocorticoids had an anti-catabolic effect on catabolic
      activated cartilage from a bovine stifle joint and murine femoral heads.
      Glucocorticoids decreased viability of all bone cells, leading to a reduction in
      osteoclastogenesis and bone resorption; however, bone morphogenetic protein 2
      stimulated osteoblasts increased bone formation, as opposed to non-stimulated
      osteoblasts. CONCLUSIONS: Using highly robust in vitro models of bone and
      cartilage turnover, we suggest that effects of glucocorticoids highly depend on
      the activation and differential stage of the cell targeted in the joint. Present
      data indicated that glucocorticoid treatment may be beneficial for articular
      cartilage, although detrimental effects on bone should be taken into account.

PMID- 21855559
TI  - Population-epigenetic models of selection.
AB  - There is increasing evidence that epigenetic modifications can be passed from one
      generation to the next. The population-level consequence of these discoveries,
      however, remains largely unexplored. In this paper, we introduce and analyze some
      simple models of constant viability selection acting on such heritable epigenetic
      variation. These "population-epigenetic" models are analogous to those of
      traditional population genetics, and are a preliminary step in quantifying the
      effect of non-genomic transgenerational inheritance, aiming to improve our
      understanding of how this sort of environmental response may affect evolution.

PMID- 21855560
TI  - Excitatory repetitive transcranial magnetic stimulation over the dorsolateral
      prefrontal cortex does not affect perceptual filling-in in healthy volunteers.
AB  - Collinear flankers increase the reports of the target present, an effect
      attributed to excitatory activation induced by the flankers on the target
      location, which consequently induces the filling-in effect (Polat & Sagi, 2007).
      Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool for non
      invasive investigation of neural processing in the human brain. We explored how
      rTMS over the left dorsolateral prefrontal cortex (LDLPFC) affects filling-in
      perception in normal controls. Active and Sham rTMS were used over the DLPFC (90%
      of the subjects' motor threshold (MT)) using 10-Hz pulses for 5- and 20-s
      intertrain intervals. We used the filling-in paradigm to probe hit rates (pHit)
      and false-positive reports (false alarm, pFA). We found that the changes in the
      filling-in effect (pHit, pFA) were not significantly different between the
      groups. However, the reaction time (RT) was significantly reduced in the rTMS
      group but not in the Sham group. Our results suggest that neural processing in
      this area is not critical in the processing of the filling-in effect, probably
      because this process is mediated by lower-level visual processing.

PMID- 21855561
TI  - Curcumin-mediated lifespan extension in Caenorhabditis elegans.
AB  - Curcumin is the active ingredient in the herbal medicine and dietary spice,
      turmeric (Curcuma longa). It has a wide range of biological activities, including
      anti-inflammatory, antioxidant, chemopreventive, and chemotherapeutic activities.
      We examined the effects of curcumin on the lifespan and aging in Caenorhabditis
      elegans, and found that it responded to curcumin with an increased lifespan and
      reduced intracellular reactive oxygen species and lipofuscin during aging. We
      analyzed factors that might influence lifespan extension by curcumin. We showed
      that lifespan extension by curcumin in C. elegans is attributed to its
      antioxidative properties but not its antimicrobial properties. Moreover, we
      showed that lifespan extension had effects on body size and the pharyngeal
      pumping rate but not on reproduction. Finally, lifespan tests with selected
      stress- and lifespan-relevant mutant strains revealed that the lifespan-extending
      phenotype was absent from the osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1, and
      age-1 mutants, whereas curcumin treatment prolonged the lifespan of mev-1 and daf
      16 mutants. Our study has unraveled a diversity of modes of action and signaling
      pathways to longevity and aging with curcumin exposure in vivo.

PMID- 21855562
TI  - The rate of ATP export in the extramitochondrial phase via the adenine nucleotide
      translocator changes in aging in mitochondria isolated from heart left ventricle
      of either normotensive or spontaneously hypertensive rats.
AB  - To find out whether and how deficit of cellular energy supply from mitochondria
      to cytosol occurs in aging and hypertension, we used mitochondria isolated from 5
      to 72 week-old heart left ventricle of either normotensive (WKY) or spontaneous
      hypertensive (SH) rats as a model system. Measurements were made of the rate of
      ATP appearance outside mitochondria, due to externally added ADP, as an increase
      of NADPH absorbance which occurs when ATP is produced in the presence of glucose,
      hexokinase and glucose-6-phosphate dehydrogenase. Such a rate proved to mirror
      the function of the adenine nucleotide translocator (ANT) rather than other
      processes linked to the both oxidative and substrate level phosphorylation. The
      changes in both Ki for atractyloside and Km for ADP suggest the occurrence of
      modification of the ANT conformation during aging in which the ANT Vmax was found
      to decrease in normotensive but to increase under spontaneously hypertension in
      24 week-old rats with a subsequent decrease in both cases. ANT function, as
      investigated in the ADP physiological range (20-60MUM), is expected to decrease
      in normotensive, but to increase in hypertensive rats up to 48 weeks. Later a
      decrease in the ATP rate of export outside mitochondria should occur in both
      cases.

PMID- 21855563
TI  - Transcriptional changes of secreted Wnt antagonists in hindlimb skeletal muscle
      during the lifetime of the C57BL/6J mouse.
AB  - The canonical Wnt pathway plays a critical role in myogenesis and age-related
      inefficient muscle regeneration. To gain insights into changes in Wnt signaling
      in muscle during the lifetime of a mouse, mRNA levels of secreted Wnt antagonists
      were investigated. Among 13 analyzed antagonists, seven genes were found to be
      down-regulated in skeletal muscles of adult and old mice. Epigenetic
      modifications at the promoter regions of these seven Wnt antagonists were then
      examined to understand how these correlate with this transcriptional repression.
      DNA methylation was stably maintained, while chromatin modifications changed to
      transcriptionally inactive states over the course of a lifetime. Similar patterns
      of changes in chromatin modifications were observed at the promoters of all of
      the studied genes. The observations indicated that an upstream factor might
      regulate the chromatin states and the transcriptional repression of Wnt
      antagonists. Several bioinformatic analyses revealed that a FOXD3 binding motif
      is present within promoter regions of the seven antagonists. Furthermore, age
      dependent differential FOXD3 binding is observed at the motifs of the seven gene
      promoters. Our results suggest that FOXD3 as a potential epigenetic regulator may
      mediate the transcriptional repression of the seven antagonists, possibly through
      regulation of histone modifications.

PMID- 21855564
TI  - Computer-aided studies on the regulation of oxidative phosphorylation during work
      transitions.
AB  - In the present polemic paper the application of computer models of oxidative
      phosphorylation (OXPHOS) in heart, skeletal muscle and liver to the studies on
      the regulation of the bioenergetic system in intact cells during work transitions
      is discussed. Two groups of such models are compared: group I models that involve
      only a direct activation of ATP usage by Ca2+, and group II models that assume a
      direct activation by some (probably) Ca2+-related mechanism of essentially all
      steps of the system. It is argued that group II models reproduce much better a
      broad range of variable values and system properties encountered in experimental
      studies. The consequences of the theoretical and experimental development of
      Metabolic Control Analysis, within the framework of which it has been shown that
      the control over the flux through the oxidative phosphorylation system is shared
      by essentially all components of this system, are analyzed. In particular, it is
      argued that in order to increase the flux very significantly, and at the same
      time to maintain relatively constant concentrations of such intermediate
      metabolites as ADP, ATP, P(i), PCr and NADH, it is necessary to activate directly
      many, if not all components of the system (the 'multi-step parallel activation'
      mechanism). Generally, it is suggested that this is not a particular form or
      complexity of computer models, but rather their agreement with a broad range of
      experimental data concerning 'macroscopic' system properties that really matters.
      The specificity of the regulation of the energetic system of pancreatic beta
      cells is discussed.

PMID- 21855566
TI  - 1,3-beta-Glucanase from Vigna aconitifolia and its possible use in enzyme
      bioreactor fabrication.
AB  - Endo-1,3(4)-beta-glucanase (EC 3.2.1.6) from Vigna aconitifolia sprouts was
      purified to 14.5 fold by gel filtration and ion-exchange chromatography. The
      enzyme was found to be a glycoprotein, its activity was Ca(2+) dependent and
      specific for beta-1,3 linkages in different polysaccharides. The K(m) value of
      the enzyme was estimated to be 3.0 mg ml(-1) for beta-D-glucan as substrate.
      Circular dichroism studies revealed 8% alpha-helix, 48% beta-pleated and 44%
      random coil in its secondary structure. Purified beta-glucanase was then
      successfully co-immobilized with glucose oxidase in agarose-chitosan beads,
      showing better immobilization yield, operational range and stability as compared
      with the crude beta-glucanase beads. The immobilized beta-glucanase was
      successfully used for mini-bioreactor fabrication.

PMID- 21855567
TI  - The building block structure of barley amylopectin.
AB  - Amylopectin branchpoints are present in amorphous lamellae of starch granules and
      organised into densely branched areas, referred to as building blocks. One single
      amylopectin cluster contains several building blocks. This study investigated the
      building block structure of domains (groups of clusters) and clusters in four
      different barley genotypes. Two of the barleys possessed the amo1 mutation,
      Glacier Ac38 and the double recessive SW 49427 with both wax and amo1 mutations,
      and were compared with the two waxy type barleys Cinnamon and Cindy. A previous
      detailed study on these four barley genotypes showed that the amo1 mutation
      affected the internal structure of amylopectin as manifested in the composition
      of clusters. In this work the building blocks were isolated from domains and
      clusters by extensive treatment with liquefying alpha-amylase of Bacillus
      subtilis and structurally characterised with enzymatic and chromatographic
      techniques. The proportion of large building blocks with a high number of chains
      was increased in the amo1 barleys, and the chain length between the blocks was
      short, which explained the previous findings of large clusters with more dense
      structure in the amo1 amylopectins.

PMID- 21855568
TI  - Applications of beta-gal-III isozyme from Bacillus coagulans RCS3, in lactose
      hydrolysis.
AB  - Bacillus coagulans RCS3 isolated from hot water springs secreted five isozymes
      i.e. beta-gal I-V of beta-galactosidase. beta-gal III isozyme was purified using
      DEAE cellulose and Sephadex G 100 column chromatography. Its molecular weight
      characterization showed a single band at 315kD in Native PAGE, while two subunits
      of 50.1 and 53.7 kD in SDS PAGE. beta-Gal III had pH optima in the range of 6-7
      and temperature optima at 65 degrees C. It preferred nitro-aryl-beta-d
      galactoside as substrate having K(m) of 4.16 mM with ONPG. More than 85% and 80%
      hydrolysis of lactose (1-5%, w/v) was recorded within 48 h of incubation at 55
      degrees C and 50 degrees C respectively and pH range of 6-7. About 78-86%
      hydrolysis of lactose in various brands of standardized milk was recorded at
      incubation temperature of 50 degrees C. These results marked the applications of
      beta-gal III in processing of milk/whey industry.

PMID- 21855565
TI  - Extended access methamphetamine decreases immature neurons in the hippocampus
      which results from loss and altered development of neural progenitors without
      altered dynamics of the S-phase of the cell cycle.
AB  - Methamphetamine addicts demonstrate impaired hippocampal-dependent cognitive
      function that could result from methamphetamine-induced maladaptive plasticity in
      the hippocampus. Reduced adult hippocampal neurogenesis observed in a rodent
      model of compulsive methamphetamine self-administration partially contributes to
      the maladaptive plasticity in the hippocampus. The potential mechanisms
      underlying methamphetamine-induced inhibition of hippocampal neurogenesis were
      identified in the present study. Key aspects of the cell cycle dynamics of
      hippocampal progenitors, including proliferation and neuronal development, were
      studied in rats that intravenously self-administered methamphetamine in a limited
      access (1h/day: short access (ShA)-4 days and ShA-13 days) or extended access
      (6h/day: long access (LgA)-4 days and LgA-13 days) paradigm. Immunohistochemical
      analysis of Ki-67 cells with 5-chloro-2'-deoxyuridine (CldU) demonstrated that
      LgA methamphetamine inhibited hippocampal proliferation by decreasing the
      proliferating pool of progenitors that are in the synthesis (S)-phase of the cell
      cycle. Double S-phase labeling with CldU and 5-iodo-2'-deoxyuridine (IdU)
      revealed that reduced S-phase cells were not due to alterations in the length of
      the S-phase. Further systematic analysis of Ki-67 cells with GFAP, Sox2, and DCX
      revealed that LgA methamphetamine-induced inhibition of hippocampal neurogenesis
      was attributable to impairment in the development of neuronal progenitors from
      preneuronal progenitors to immature neurons. Methamphetamine concomitantly
      increased hippocampal apoptosis, changes that were evident during the earlier
      days of self-administration. These findings demonstrate that methamphetamine self
      administration initiates allostatic changes in adult neuroplasticity maintained
      by the hippocampus, including increased apoptosis, and altered dynamics of
      hippocampal neural progenitors. These data suggest that altered hippocampal
      plasticity by methamphetamine could partially contribute to methamphetamine
      induced impairments in hippocampal function.

PMID- 21855569
TI  - A comparative study of antimicrobial properties of crustinPm1 and crustinPm7 from
      the black tiger shrimp Penaeus monodon.
AB  - Several isoforms of crustin have been identified in the black tiger shrimp
      Penaeus monodon. These cationic cysteine-rich antimicrobial peptides contain a
      single whey acidic protein (WAP) domain at the C-terminus and exhibit
      antimicrobial activity against both Gram-positive and Gram-negative bacteria. In
      this paper, we investigate the binding properties and antimicrobial actions of
      crustinPm1 and crustinPm7, the two most abundant crustin isoforms found in the
      haemocyte of P. monodon. Previously, crustinPm1 showed strong inhibition against
      Gram-positive bacteria, whilst crustinPm7 acted against both Gram-positive and
      Gram-negative bacteria. A binding study showed that both crustins can bind to
      Gram-positive and Gram-negative bacterial cells. Enzyme-linked immunosorbent
      (ELISA) assay suggested that crustins bind to the cell wall components,
      lipoteichoic acid (LTA) and lipopolysaccharide (LPS) with positive cooperativity
      of Hill slope (H)>2. This indicates that at least two molecules of crustins
      interact with one LTA or LPS molecule. In addition, both crustins can induce
      bacterial agglutination and cause inner membrane permeabilization in Escherichia
      coli. Scanning Electron Microscopy (SEM) revealed the remarkable change on the
      cell surface of Staphylococcus aureus, Vibrio harveyi and E. coli after the
      bacteria were treated with the recombinant crustinPm7. Meanwhile, crustinPm1 can
      cause a visible change on the cell surface of S. aureus and E. coli only. This is
      in agreement with the fact that crustinPm1 has shown no antimicrobial activity
      against V. harveyi. It is likely that the antimicrobial activity of crustins
      mainly relies on their ability to agglutinate bacterial cells and to disrupt the
      physiochemical properties of bacterial surface.

PMID- 21855570
TI  - Overexpression of NF-kappaB inhibitor alpha in Cynoglossus semilaevis impairs
      pathogen-induced immune response.
AB  - IkappaBalpha is a member of the NF-kappaB inhibitor family that inhibits NF
      kappaB activity by sequestering NF-kappaB in an inactive form in the cytosol.
      Unlike mammalian IkappaBalpha, which has been extensively studied, very little is
      known about the function of fish IkappaBalpha. In this study, we identified and
      analyzed an IkappaBalpha homologue, CsIkappaBalpha from half-smooth tongue sole
      (Cynoglossus semilaevis), a marine flatfish with important economic value. The
      deduced amino acid sequence of CsIkappaBalpha contains 308 residues and shares 58
      82% overall sequence identities with the IkappaBalpha of a number of teleosts. In
      silico analysis identified in CsIkappaBalpha conserved domains that in mammals
      are known to be involved in phosphorylation, ubiquitination, and degradation of
      IkappaBalpha. Quantitative real time RT-PCR detected constitutive expression of
      CsIkappaBalpha in gut, spleen, liver, gill, heart, brain, muscle, and kidney.
      Experimental challenge with a bacterial pathogen-induced significant inductions
      of CsIkappaBalpha expression in head and trunk kidney, which, however, were
      transient and much lower in magnitude than that of interleukin-1beta. To examine
      the effect of unregulated overexpression of CsIkappaBalpha in a live fish model,
      tongue sole were administered via intramuscular injection with plasmid pCNCsIkBa,
      which constitutively expresses CsIkappaBalpha. PCR, RT-PCR, and
      immunohistochemistry analysis showed that pCNCsIkBa was able to translocate to
      internal tissues, where transcription and translation of the recombinant
      CsIkappaBalpha took place. Compared to control fish, fish administered with
      pCNCsIkBa were impaired in the ability to block bacterial dissemination and
      survival in kidney and exhibited significantly reduced expression of multiple
      immune genes. These results suggest the possible existence in tongue sole of a NF
      kappaB-IkappaBalpha signaling pathway that is negatively regulated by
      CsIkappaBalpha and required for effective defense against bacterial infection.

PMID- 21855571
TI  - Social fearfulness in the human brain.
AB  - Social fearfulness is expressed on a continuum of severity from moderate distress
      to incapacitating fear. The present article focuses on the brain states
      associated with this broad dimension of social anxiety in humans. In total, 70
      published studies are summarized documenting the neural correlates of social
      anxiety during states of rest, threat-related cognitive-affective activation, and
      acute symptom provocation. Neural exaggeration in limbic (amygdala) and
      paralimbic (insula) regions appears to be associated with functional outcomes
      involving increased attention for and processing of social threat. Evidence is
      also reviewed showing that social anxiety is characterized by atypical functional
      connectivity in certain brain networks. Despite a higher prevalence of social
      anxiety disorder among females, males have been overrepresented in the published
      clinical studies (constituting approximately 56% of the total participants). We
      evaluate the prospects of nonhuman animal models of social anxiety and discuss
      several promising directions for future research. The review highlights the need
      to adopt an integrative, network-based approach to the study of the neural
      substrates underlying social anxiety.

PMID- 21855572
TI  - Protective effect of Nigella sativa oil against tramadol-induced tolerance and
      dependence in mice: role of nitric oxide and oxidative stress.
AB  - Nigella sativa seed extracts and its oil have been exploited for their various
      health benefits. In this study, the effects of N. sativa oil on tramadol-induced
      tolerance and dependence and possible mechanism(s) of these effects were
      investigated, for the first time, in mice. Repeated administration of N. sativa
      oil (4 ml/kg, p.o.) along with tramadol (50mg/kg, s.c.) inhibited the development
      of tramadol tolerance, as measured by the hot plate test, and dependence as
      assessed by naloxone (5mg/kg, i.p.)-precipitated withdrawal manifestations.
      Concomitantly, nitric oxide overproduction and increase in brain malondialdehyde
      level induced by repeated administration of tramadol to mice or by administration
      of naloxone to tramadol-dependent mice were inhibited by co-administration of the
      oil. Also, the decrease in brain intracellular reduced glutathione level and
      glutathione peroxidase activity induced by both treatments was inhibited by co
      administration of the oil. The increase in brain glutamate level induced by both
      treatments was not inhibited by concurrent administration of the oil. The
      inhibitory effect of N. sativa oil on tramadol-induced tolerance and dependence
      was enhanced by concurrent i.p. administration of the NMDA receptor antagonist,
      dizocilpine (0.25mg/kg). Also, the inhibitory effect of the oil on naloxone
      induced biochemical alterations in tramadol-dependent mice was enhanced by
      concurrent administration of dizocilpine. Similarly, concurrent i.p.
      administration of the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester
      (10mg/kg) or the antioxidant, N-acetylcysteine (50mg/kg) enhanced these
      inhibitory effects of N. sativa oil. On the other hand, these effects were
      antagonized by concurrent i.p. administration of the NO precursor, L-arginine
      (300 mg/kg). These results provide evidence that N. sativa oil appears to have a
      therapeutic potential in tramadol tolerance and dependence through blockade of NO
      overproduction and oxidative stress induced by the drug.

PMID- 21855573
TI  - Soluble markers of inflammation are associated with Framingham scores in HIV
      infected patients on suppressive antiretroviral therapy.
AB  - OBJECTIVE: To evaluate the association between biomarkers of inflammation and
      endothelial dysfunction and Framingham scores (FS) for risk of coronary heart
      disease (FS-CHD), stroke (FS-Stroke) or any cardiovascular event (FS-CVE) in HIV
      infected on suppressive highly active antiretroviral therapy (HAART). METHODS: A
      cross-sectional study was conducted in 73 HIV-infected patients and 23 healthy
      controls. Inflammatory molecules and endothelial dysfunction markers were
      measured using a multiplex immunoassay (plasminogen activator inhibitor type 1
      (PAI-1), soluble TNF receptor type 1 (sTNF-R1), soluble CD40 ligand (sCD40L),
      soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble
      intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion
      molecule (sVCAM-1). Outcome variables were FS-CHD >=10%, FS-Stroke >=5% and FS
      CVE >=10%. RESULTS: Significant differences (p < 0.05) were found comparing
      controls and HIV patients for PAI-1 (5.4 vs. 13.5 ng/dL), sTNF-R1 (0.85 vs. 1.09
      ng/dL), sICAM-1 (529 vs. 858 ng/dL), sE-selectin (73.7 vs. 120 ng/dL), sP
      selectin (676 vs. 1511 ng/dL) sCD40L (76 vs. 307 ng/dL), FS-CHD (4% vs. 7.8% L),
      FS-Stroke (2% vs. 2.8%) and FS-CVE (5% vs. 11%). In HIV-infected patients, the
      adjusted logistic regression analysis revealed that sTNF-R1 levels were
      significantly associated with increased FS-CHD>10% (OR: 11.51 (95% CI: 1.14;
      115.84); p = 0.038) and FS-CVE (OR: 12.41 (95% CI: 1.25; 123.23); p = 0.031).
      CONCLUSIONS: HIV-infected patients show higher levels of soluble inflammatory and
      endothelial dysfunction markers than controls and have a two-fold increased FS of
      presenting coronary heart disease, stroke or cardiovascular events at 10 years.
      Furthermore, sTNF-R1 displayed the best association with FS of coronary heart
      disease and any cardiovascular event in our patients.

PMID- 21855574
TI  - Temporal profile of arginine vasopressin release from the neurohypophysis in
      response to hypertonic saline and hypotension measured using a fluorescent fusion
      protein.
AB  - Methods currently employed to study the release of hormones such as arginine
      vasopressin (AVP), while sensitive, suffer from a low temporal resolution such
      that the monitoring of AVP release on a moment-to-moment basis is not possible.
      Here, we describe a new approach to indirectly monitor the temporal profile of
      AVP release from the neurohypophysis of transgenic rats expressing an AVP-eGFP
      fusion gene. Using fibre-optic probes (termed 'optrodes') we were able to
      indirectly monitor AVP release via a reporter moiety in real-time. This method is
      a major advance over current methods used to monitor AVP release. Intravenous
      administration of hypertonic saline (3M NaCl) induced a rapid (latency of 2-3s)
      increase in fluorescence detected in the neurohypophysis that lasted on average
      for 60s - a response that was highly reproducible. Infusion of sodium
      nitroprusside induced a rapid fall in blood pressure accompanied by a rapid,
      stimulus-locked increase in fluorescent signal that returned to baseline with the
      recovery of blood pressure to pre-stimulus levels - again this response was
      highly reproducible. Withdrawal of blood (to simulate haemorrhage) also resulted
      in a stimulus-locked increase in fluorescence that return to baseline after the
      withdrawn blood was returned to the animal. In conclusion, we developed a highly
      sensitive approach that allows the indirect measurement of AVP release via the
      monitoring of a reporter gene in real-time. This technology can be adapted to
      permit the study of a whole array of neurohormones/chemicals in transgenic
      animals expressing a fluorescent reporter construct.

PMID- 21855575
TI  - A high-throughput screening assay of ascorbate in brain samples.
AB  - Ascorbate is a vital reductant/free radical scavenger in the CNS, whose content
      defines - to a large extent - the redox status and the antioxidant reserves.
      Quick, reliable and specific methods for its measurement in brain samples are
      highly desirable. We have developed a new high-throughput screening assay for
      measurements of ascorbate using a fluorescence plate-reader. This assay is based
      on a direct reaction of ascorbate with a nitroxide radical conjugated with a
      fluorogenic acridine moiety, 4-((9-acridinecarbonyl)-amino)-2,2,6,6
      tetramethylpiperidine-1-oxyl radical (AC-TEMPO), yielding fluorescent
      hydroxylamine product (AC-TEMPO-H). The reaction was monitored over time using
      fluorescence and electron spin resonance techniques. The appearance of
      fluorescent AC-TEMPO-H was linear within the range of 3.75-75MUM AscH(-) in the
      sample (0.5-10MUM AscH(-) in the well). Assay was validated with high performance
      liquid chromatography method. The concentration of ascorbate in murine tissue
      samples, including brain samples after traumatic brain injury and hemorrhagic
      shock, was measured.

PMID- 21855576
TI  - A new method for visualization of endothelial cells and extravascular leakage in
      adult mouse brain using fluorescein isothiocyanate.
AB  - We described a new method for the visualization of vasculature and endothelial
      cells and the assessment of extravascular leakage in adult mouse brain by using
      fluorescein isothiocyanate (FITC), or a reactive fluorescent dye. FITC is the
      fluorescein derivative that reacts covalently with amine groups at alkaline pH.
      In this method, strong fluorescence of FITC was seen at vasculature throughout
      the brain and spinal cord, when mice received intracardiac perfusion with FITC
      containing saline at pH 7.0 followed by paraformaldehyde (PFA) fixative at pH
      8.0. The fluorescence of FITC was faint when animals were fixed with PFA fixative
      at pH 7.0 after the perfusion of FITC-containing saline at pH 7.0. The
      fluorescence of FITC was not detected when mice was fixed with PFA fixative
      before the perfusion of FITC-containing saline. Double labeling
      immunohistochemistry using an endothelial cell marker CD31 or a pericyte marker
      desmin revealed that FITC was accumulated at nuclei of endothelial cells but not
      at those of pericytes. Extravascular leakage of FITC was prominent in the area
      postrema or a brain region of the circumventricular organs that lacks the blood
      brain barrier. Moreover, strong extravascular leakage of FITC was detected at
      damaged sites of the cerebral cortex with cryoinjury. Thus, FITC method is useful
      technique for examining the architecture of brain vasculature and endothelial
      cells and the assessment of extravascular leakage in adult rodents. Moreover,
      FITC binds covalently to cellular components, so that makes it possible to
      perform double labeling immunohistochemistry and long-term storage of the
      preparation.

PMID- 21855577
TI  - Lentiviral vectors express chondroitinase ABC in cortical projections and promote
      sprouting of injured corticospinal axons.
AB  - Several diseases and injuries of the central nervous system could potentially be
      treated by delivery of an enzyme, which might most effectively be achieved by
      gene therapy. In particular, the bacterial enzyme chondroitinase ABC is
      beneficial in animal models of spinal cord injury. We have adapted the
      chondroitinase gene so that it can direct secretion of active chondroitinase from
      mammalian cells, and inserted it into lentiviral vectors. When injected into
      adult rat brain, these vectors lead to extensive secretion of chondroitinase,
      both locally and from long-distance axon projections, with activity persisting
      for more than 4 weeks. In animals which received a simultaneous lesion of the
      corticospinal tract, the vector reduced axonal die-back and promoted sprouting
      and short-range regeneration of corticospinal axons. The same beneficial effects
      on damaged corticospinal axons were observed in animals which received the
      chondroitinase lentiviral vector directly into the vicinity of a spinal cord
      lesion.

PMID- 21855578
TI  - Detection and absolute quantitation of Broad bean wilt virus 1 (BBWV-1) and BBWV
      2 by real time RT-PCR.
AB  - Broad bean wilt virus 1 (BBWV-1) and BBWV-2 are the two most significant viruses
      in the genus Fabavirus, causing damage to many economically important
      agricultural crops worldwide. A quantitative real-time reverse transcription
      polymerase chain reaction (RT-qPCR) procedure using two TaqMan((r))MGB probes was
      developed for sensitive and specific detection and quantitation of BBWV-1 and
      BBWV-2. Primers and probes were designed from conserved sequence stretches to
      detect all isolates of each virus. Standard curves using RNA transcripts
      identical to both TaqMan((r))MGB probes enabled absolute quantitation, with a
      wide dynamic range and high sensitivity (10(3)-10(10) RNA molecules). RT-qPCR was
      assayed with genetically divergent BBWV-1 and BBWV-2 isolates from different
      plant hosts and countries, and was used to evaluate the temporal accumulation of
      BBWV-1 RNA in two plant hosts.

PMID- 21855579
TI  - Predatory threat induces huddling in adolescent rats and residual changes in
      early adulthood suggestive of increased resilience.
AB  - Adolescence is a critical developmental period during which chronic stress and
      binge alcohol consumption are often seen as environmental risk factors that
      confer vulnerability to later mental health problems. The current study modelled
      this using a 2*2 design where male Wistar rats were exposed to intermittent
      predatory stress (Stress condition: groups of 4 rats given 30 min of cat fur
      exposure in a large arena, once every 48 h) or intermittent alcohol (Alcohol
      condition: access to beer for 24 h every 2nd day), or both manipulations given on
      alternate days (Stress/Alcohol), or no manipulation (Control). The manipulations
      occurred over a 24 day adolescent window (postnatal day (PND) 33-57) giving a
      total of 12 cat fur exposures and/or 12 alternate days of beer access. Residual
      anxiety- and depressive-like behaviours were assessed in early adulthood (PND 58
      77). Cat fur exposure was found to elicit a distinct defensive response in which
      groups of adolescent rats huddled together in the corner of the arena, either in
      "quads" (all 4 rats bunched together) or "triplets" (3 rats together and one
      outlier rat). Few approaches to the cat fur occurred and locomotor activity was
      suppressed relative to Control rats placed in the arena without fur. Huddling
      continued over the 12 repeated exposures to cat fur, and was temporarily
      exaggerated when fur from a novel cat was introduced. Interestingly, huddling and
      conditioned fear in the fur-associated context were most pronounced in rats
      receiving intermittent alcohol, suggesting that alternate day exposure to alcohol
      had anxiogenic effects, possibly linked to a hangover state on these days.
      Predatory stress did not affect overall alcohol consumption relative to rats
      given alcohol alone, but significantly inhibited weight gain through adolescence
      and into adulthood. In early adulthood, rats exposed to stress in adolescence,
      regardless of alcohol exposure, showed significantly reduced immobility in the
      forced swim test and signs of increased sociability with a novel conspecific in a
      social interaction paradigm. Overall, these findings suggest greater resilience
      in adulthood after chronic adolescent stress, indicating that coping with
      predators may be in some ways a form of early environmental enrichment.

PMID- 21855580
TI  - Assessment of rewarding and reinforcing properties of biperiden in conditioned
      place preference in rats.
AB  - Biperiden is one of the most commonly abused anticholinergic drugs. This study
      assessed its motivational effects in the acquisition of conditioned place
      preference in rats. Biperiden neither produced place conditioning itself nor
      enhanced the rewarding effect of morphine. Furthermore, biperiden in combination
      with haloperidol also did not affect place preference. These findings suggest
      that biperiden seems devoid of abuse potential properties at least at the doses
      used.

PMID- 21855581
TI  - Periostin mediates human adipose tissue-derived mesenchymal stem cell-stimulated
      tumor growth in a xenograft lung adenocarcinoma model.
AB  - Mesenchymal stem cells stimulate tumor growth in vivo through a lysophosphatidic
      acid (LPA)-dependent mechanism. However, the molecular mechanism by which
      mesenchymal stem cells stimulate tumorigenesis is largely elusive. In the present
      study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma
      cells (A549 CM) induces expression of periostin, an extracellular matrix protein,
      in human adipose tissue-derived mesenchymal stem cells (hASCs). A549 CM
      stimulated periostin expression was abrogated by pretreatment of hASCs with the
      LPA receptor 1 (LPA(1)) inhibitor Ki16425 or short hairpin RNA-mediated silencing
      of LPA(1), suggesting a key role of the LPA-LPA(1) signaling axis in A549 CM
      stimulated periostin expression. Using a xenograft transplantation model of A549
      cells, we demonstrated that co-injection of hASCs potentiated tumor growth of
      A549 cells in vivo and that co-transplanted hASCs expressed not only periostin
      but also alpha-smooth muscle actin (alpha-SMA), a marker of carcinoma-associated
      fibroblasts. Small interfering RNA- or short hairpin RNA-mediated silencing of
      periostin resulted in blockade of LPA-induced alpha-SMA expression in hASCs. In
      addition, silencing of periostin resulted in blockade of hASC-stimulated growth
      of A549 xenograft tumors and in vivo differentiation of transplanted hASCs to
      alpha-SMA-positive carcinoma-associated fibroblasts. Conditioned medium derived
      from LPA-treated hASCs (LPA CM) potentiated proliferation and adhesion of A549
      cells and short interfering RNA-mediated silencing or immunodepletion of
      periostin from LPA CM abrogated proliferation and adhesion of A549 cells. These
      results suggest a pivotal role for hASC-secreted periostin in growth of A549
      xenograft tumors within the tumor microenvironment.

PMID- 21855582
TI  - Prospective associations between cardiovascular reactions to acute psychological
      stress and change in physical disability in a large community sample.
AB  - Exaggerated haemodynamic reactions to acute psychological stress have been
      implicated in cardiovascular disease outcomes, while lower reactions have been
      considered benign. This study examined, in a large cohort, the prospective
      associations between stress reactivity and physical disability. Blood pressure
      and pulse rate were measured at rest and in response to a stress task. Physical
      disability was assessed using the OPCS survey of disability at baseline and five
      years later. Heart rate reactivity was negatively associated with change in
      physical disability over time, such that those with lower heart rate reactivity
      were more likely to deteriorate over the following five years. These effects
      remained significant following adjustment for a number of confounding variables.
      These data give further support to the recent argument that for some health
      outcomes, lower or blunted cardiovascular stress reactivity is not necessarily
      protective.

PMID- 21855584
TI  - Protein-excipient interactions: mechanisms and biophysical characterization
      applied to protein formulation development.
AB  - The purpose of this review is to demonstrate the critical importance of
      understanding protein-excipient interactions as a key step in the rational design
      of formulations to stabilize and deliver protein-based therapeutic drugs and
      vaccines. Biophysical methods used to examine various molecular interactions
      between solutes and protein molecules are discussed with an emphasis on
      applications to pharmaceutical excipients in terms of their effects on protein
      stability. Key mechanisms of protein-excipient interactions such as electrostatic
      and cation-pi interactions, preferential hydration, dispersive forces, and
      hydrogen bonding are presented in the context of different physical states of the
      formulation such as frozen liquids, solutions, gels, freeze-dried solids and
      interfacial phenomenon. An overview of the different classes of pharmaceutical
      excipients used to formulate and stabilize protein therapeutic drugs is also
      presented along with the rationale for use in different dosage forms including
      practical pharmaceutical considerations. The utility of high throughput
      analytical methodologies to examine protein-excipient interactions is presented
      in terms of expanding formulation design space and accelerating experimental
      timelines.

PMID- 21855583
TI  - Impact of reward and punishment motivation on behavior monitoring as indexed by
      the error-related negativity.
AB  - The error-related negativity (ERN) is thought to index a neural behavior
      monitoring system with its source in anterior cingulate cortex (ACC). While ACC
      is involved in a wide variety of cognitive and emotional tasks, there is debate
      as to what aspects of ACC function are indexed by the ERN. In one model the ERN
      indexes purely cognitive function, responding to mismatch between intended and
      executed actions. Another model posits that the ERN is more emotionally driven,
      elicited when an action is inconsistent with motivational goals. If the ERN
      indexes mismatch between intended and executed actions, then it should be
      insensitive to motivational valence, e.g. reward or punishment; in contrast if
      the ERN indexes the evaluation of responses relative to goals, then it might
      respond differentially under differing motivational valence. This study used a
      flanker task motivated by potential reward and potential punishment on different
      trials and also examined the N2 and P3 to the imperative stimulus, the response
      Pe, and the FRN and P3 to the outcome feedback to assess the impact of motivation
      valence on other stages of information processing in this choice reaction time
      task. Participants were slower on punishment motivated trials and both the N2 and
      ERN were larger on punishment motivated trials, indicating that loss aversion has
      an impact on multiple stages of information processing including behavior
      monitoring.

PMID- 21855585
TI  - Neatness counts. How plating affects liking for the taste of food.
AB  - Two studies investigated the effect that the arrangement of food on a plate has
      on liking for the flavor of the food. Food presented in a neatly arranged
      presentation is liked more than the same food presented in a messy manner. A
      third study found that subjects expected to like the food in the neat
      presentations more than in the messy ones and would be willing to pay more for
      them. They also indicated that the food in the neat presentations came from a
      higher quality restaurant and that more care was taken with its preparation than
      the food in the messy presentations. Only the animal-based food was judged as
      being more contaminated when presented in a messy rather than a neat way.
      Neatness of the food presentation increases liking for the taste of the food by
      suggesting greater care on the part of the preparer. Two mechanisms by which
      greater care might increase liking are discussed.

PMID- 21855586
TI  - Fat emulsion composition alters intake and the effects of baclofen.
AB  - Thickened oil-in-water emulsions are useful model foods in rat studies due to
      their high acceptance and similarity to foods consumed by humans. Previous work
      from this laboratory used oil-in-water emulsions thickened with a biopolymer
      blend containing starch. Intake and effects of baclofen, a GABA-B agonist that
      decreases fat intake and drug self-administration, were reported, but the
      contribution of starch was not assessed. In the present study, intake and effects
      of baclofen were assessed in rats using emulsions prepared with two fat types
      (32% vegetable shortening, 32% corn oil) and thickened with three biopolymer
      blends. One biopolymer blend contained starch and the other two did not. Daily 1
      h intake of the vegetable shortening emulsion containing starch was significantly
      greater than the other emulsions. When starch was added to the emulsions
      originally containing no starch, intake significantly increased. Baclofen
      generally reduced intake of all emulsions regardless of starch content and
      stimulated intake of chow. However, effects were more often significant for
      vegetable shortening emulsions. This report: (1) demonstrates that products used
      to prepare thickened oil-in-water emulsions have significant effects on rat
      ingestive behavior, and (2) confirms the ability of baclofen to reduce
      consumption of fatty foods, while simultaneously stimulating intake of chow.

PMID- 21855587
TI  - Acute effect of soybean beta-conglycinin hydrolysate ingestion on appetite
      sensations in healthy humans.
AB  - A hydrolysate prepared from soybean beta-conglycinin reduced food intake through
      cholecystokinin release in rats; however, effects of the hydrolysate on human
      appetites are unknown. In this study, healthy volunteers ingested 3g of the beta
      conglycinin hydrolysate (BconB) and/or a soy protein hydrolysate (HN) contained
      in a beverage or in a jelly. Appetite profiles (hunger, fullness and prospective
      consumption) after the ingestion and palatability of test jellies were recorded.
      Fullness was rated higher, and hunger was rated lower after BconB ingestion as
      compared to HN ingestion. These results demonstrate that 3g of BconB is effective
      to enhance fullness and reduce hunger sensations in healthy humans.

PMID- 21855588
TI  - Effects of vaspin, chemerin and omentin-1 on feeding behavior and hypothalamic
      peptide gene expression in the rat.
AB  - Visceral adipose tissue-derived serpin (vaspin) improves glucose tolerance and
      insulin sensitivity in diet-induced obese mice. Chemerin may increase insulin
      sensitivity in adipose tissue and seems to be associated with several key aspects
      of metabolic syndrome. Decreased levels of omentin-1 are associated with
      increasing obesity and insulin resistance. Our study aimed to investigate the
      effects of vaspin, chemerin and omentin-1 acute administration on feeding and
      hypothalamic gene expression of peptides which play a key role in feeding
      regulation. 35 rats were injected into the arcuate nucleus (ARC) of the
      hypothalamus with either saline (n=8), vaspin (1MUg/kg; n=9), chemerin (8MUg/kg;
      n=9), or omentin-1 (8MUg/kg; n=9). Food intake in the following 24h was recorded,
      thereafter rats were sacrificed. Total RNA was extracted from hypothalami and
      reverse transcribed to evaluate hypothalamic gene expression of agouti-related
      peptide (AgRP), neuropeptide Y (NPY), orexin-A, cocaine- and amphetamine
      regulated transcript (CART), corticotrophin releasing hormone (CRH) and
      proopiomelanocortin (POMC), by real-time reverse transcription polymerase chain
      reaction. Compared to vehicle, vaspin injection significantly decreased feeding,
      while chemerin and omentin-1 had no effect in the tested dose. Vaspin treatment
      significantly decreased NPY and increased POMC gene expression. Chemerin
      treatment led to a significant increase of both AgRP and POMC gene expression.
      Omentin-1 treatment did not modify gene expression of the investigated peptides.
      Therefore, vaspin is an adipokine triggering anorectic pathways in the
      hypothalamus, where reduction of NPY and increase of POMC mRNA levels mediate
      feeding inhibition. Chemerin and omentin-1 have no effect on feeding in the
      tested dose.

PMID- 21855589
TI  - Chemometric analysis of Hymenoptera toxins and defensins: A model for predicting
      the biological activity of novel peptides from venoms and hemolymph.
AB  - When searching for prospective novel peptides, it is difficult to determine the
      biological activity of a peptide based only on its sequence. The "trial and
      error" approach is generally laborious, expensive and time consuming due to the
      large number of different experimental setups required to cover a reasonable
      number of biological assays. To simulate a virtual model for Hymenoptera insects,
      166 peptides were selected from the venoms and hemolymphs of wasps, bees and ants
      and applied to a mathematical model of multivariate analysis, with nine different
      chemometric components: GRAVY, aliphaticity index, number of disulfide bonds,
      total residues, net charge, pI value, Boman index, percentage of alpha helix, and
      flexibility prediction. Principal component analysis (PCA) with non-linear
      iterative projections by alternating least-squares (NIPALS) algorithm was
      performed, without including any information about the biological activity of the
      peptides. This analysis permitted the grouping of peptides in a way that strongly
      correlated to the biological function of the peptides. Six different groupings
      were observed, which seemed to correspond to the following groups: chemotactic
      peptides, mastoparans, tachykinins, kinins, antibiotic peptides, and a group of
      long peptides with one or two disulfide bonds and with biological activities that
      are not yet clearly defined. The partial overlap between the mastoparans group
      and the chemotactic peptides, tachykinins, kinins and antibiotic peptides in the
      PCA score plot may be used to explain the frequent reports in the literature
      about the multifunctionality of some of these peptides. The mathematical model
      used in the present investigation can be used to predict the biological
      activities of novel peptides in this system, and it may also be easily applied to
      other biological systems.

PMID- 21855590
TI  - An appeal to include the History of Vaccinology.

PMID- 21855591
TI  - A qualitative analysis of South African women's knowledge, attitudes, and beliefs
      about HPV and cervical cancer prevention, vaccine awareness and acceptance, and
      maternal-child communication about sexual health.
AB  - In South Africa, cervical cancer is the second leading cause of death among
      women. Black South Africa women are disproportionately affected by cervical
      cancer and have one of the highest mortality rates from this disease. Although
      the body of literature that examines HPV and cervical cancer prevention is
      growing in the developing world; there is still a need for a better understanding
      of women's knowledge and beliefs around HPV and cervical cancer prevention.
      Therefore, this formative study sought to examine women's attitudes, beliefs and
      knowledge of HPV and cervical cancer, HPV vaccine acceptance, maternal-child
      communication about sexuality, and healthcare decision-making and gender roles
      within an urban community in South Africa. Women ages 18-44 were recruited from
      an antenatal clinic in a Black township outside of Johannesburg during the fall
      of 2008. Twenty-four women participated in three focus groups. Findings indicated
      that the women talked to their children about a variety of sexual health issues;
      had limited knowledge about HPV, cervical cancer, and the HPV vaccine. Women were
      interested in learning more about the vaccine although they had reservations
      about the long-term affect; they reinforced that grandmothers played a key role
      in a mother's decisions' about her child's health, and supported the idea that
      government should provide the HPV vaccine as part of the country's immunization
      program. Our findings indicate the need to develop primary prevention strategies
      and materials that will provide women with basic cervical cancer prevention
      messages, including information about HPV, cervical cancer, the HPV vaccine,
      screening, and how to talk to their children about these topics. Prevention
      strategies should also consider the cultural context and the role that
      grandmothers play in the family unit.

PMID- 21855592
TI  - Immunogenicity and safety of intradermal influenza vaccine in children.
AB  - In order to compare the immunogenicity and safety of different doses of trivalent
      influenza vaccine (TIV) administered intradermallly (ID) with those evoked by a
      full dose of intramuscular (IM) virosomal-adjuvanted influenza vaccine (VA-TIV),
      112 previously primed healthy children aged >= 3 years were randomised to receive
      9 MUg or 15 MUg of each strain of ID-TIV, or a full IM dose (15 MUg of each
      strain) of VA-TIV. The A/H1N1 and A/H3N2 seroconversion and seroprotection rates
      were >= 90% and geometric mean titres (GMTs) increased 3.2-14.9 times without any
      statistically significant between-group differences; however, the seroconversion
      and seroprotection rates against the B strain were significantly higher in the
      children receiving either ID-TIV dose (p<0.05) without any differences between
      them. GMT against B virus was significantly higher in the children receiving the
      highest dose (p<0.05). Local reactions were significantly more common among the
      children receiving either ID-TIV dose (p<0.05), but systemic reactions were
      relatively uncommon in all three groups. Our findings suggest that ID-TIV with 15
      MUg of each viral antigen can confer a significant better protection against
      influenza than that obtained with the same dose of IM TIV in already primed
      children aged >= 3 years with an acceptable safety profile. The lower dose of ID
      TIV needs further evaluation to analyze persistence of protection.

PMID- 21855593
TI  - Opportunities to minimise animal use in pharmaceutical regulatory general
      toxicology: a cross-company review.
AB  - Toxicity studies in animals are carried out to identify the intrinsic hazard of a
      substance to support risk assessment for humans. In order to identify
      opportunities to minimise animal use in regulatory toxicology studies, a review
      of current study designs was carried out. Pharmaceutical companies and contract
      research organisations in the UK shared data and experience of standard
      toxicology studies (ranging from one to nine months duration) in rodents and non
      rodents; and carcinogenicity studies in the rat and mouse. The data show that
      variation in study designs was primarily due to (i) the number of animals used in
      the main study groups, (ii) the use of animals in toxicokinetic (TK) satellite
      groups, and (iii) the use of animals in off-treatment recovery groups. The
      information has been used to propose a series of experimental designs where small
      adjustments could reduce animal use in practice, while maintaining the scientific
      objectives.

PMID- 21855594
TI  - Interrogating health-related public databases from a food toxicology perspective:
      computational analysis of scoring data.
AB  - Over the last 15 years, an expanding number of databases with information on
      noxious effects of substances on mammalian organisms and the environment have
      been made available on the Internet. This set of databases is a key source of
      information for risk assessment within several areas of toxicology. Here we
      present features and relationships across a relatively wide set of publicly
      accessible databases broadly within toxicology, in part by clustering multi-score
      representations of such repositories, to support risk assessment within food
      toxicology. For this purpose 36 databases were each scrutinized, using 18 test
      substances from six different categories as probes. Results have been analyzed by
      means of various uni- and multi-variate statistical operations. The former
      included a special index devised to afford context-specific rating of databases
      across a highly heterogeneous data matrix, whereas the latter involved cluster
      analysis, enabling the identification of database assemblies with overall shared
      characteristics. One database - HSDB - was outstanding due to rich and qualified
      information for most test substances, but an appreciable fraction of the
      interrogated repositories showed good to decent scoring. Among the six chosen
      substance groups, Food contact materials had the most comprehensive toxicological
      information, followed by the Pesticides category.

PMID- 21855595
TI  - Fragrance material review on 3-phenyl-1-propanol.
AB  - A toxicologic and dermatologic review of 3-phenyl-1-propanol when used as a
      fragrance ingredient is presented. 3-Phenyl-1-propanol is a member of the
      fragrance structural group cinnamyl phenylpropyl compounds. The common
      characteristic structural element of cinnamyl phenylpropyl materials is an aryl
      substituted primary alcohol/aldehyde/ester. They are simple aromatic compounds
      with saturated propyl or unsaturated propenyl side chains containing a primary
      oxygenated functional group which has little toxic potential. 3-Phenyl-1-propyl
      derivatives participate in the same beta-oxidation pathways as do their parent
      cinnamic acid derivatives. This review contains a detailed summary of all
      available toxicology and dermatology papers that are related to this individual
      fragrance ingredient and is not intended as a stand-alone document. Available
      data for 3-phenyl-1-propanol was evaluated then summarized and includes physical
      properties, acute toxicity, skin irritation, skin sensitization, in vitro skin
      absorption and mutagenicity. A safety assessment of all cinnamyl phenylpropyl
      compounds will be published simultaneously with this document; please refer to
      Belsito et al. (2011) for an overall assessment of the safe use of this material
      and all cinnamyl phenylpropyl materials in fragrances (Belsito, D., Bickers, D.,
      Bruze, M., Dagli, M.L., Fryer, A., Greim, H., Miyachi, Y., Saurat, J.H., Sipes,
      I.G., 2011. A toxicologic and dermatologic assessment of cinnamyl phenylpropyl
      compounds when used as fragrance ingredients.).

PMID- 21855596
TI  - Fragrance material review on 3-phenylpropyl cinnamate.
AB  - A toxicologic and dermatologic review of 3-phenylpropyl cinnamate when used as a
      fragrance ingredient is presented. 3-Phenylpropyl cinnamate is a member of the
      fragrance structural group cinnamyl phenylpropyl compounds. The common
      characteristic structural element of cinnamyl phenylpropyl materials is an aryl
      substituted primary alcohol/aldehyde/ester. They are simple aromatic compounds
      with saturated propyl or unsaturated propenyl side chains containing a primary
      oxygenated functional group which has little toxic potential. 3-Phenyl-1-propyl
      derivatives participate in the same beta-oxidation pathways as do their parent
      cinnamic acid derivatives. This review contains a detailed summary of all
      available toxicology and dermatology papers that are related to this individual
      fragrance ingredient and is not intended as a stand-alone document. Available
      data for 3-phenylpropyl cinnamate was evaluated then summarized and includes
      physical properties, acute toxicity, skin irritation and skin sensitization. A
      safety assessment of all cinnamyl phenylpropyl compounds will be published
      simultaneously with this document. Please refer to Belsito et al. (2011) for an
      overall assessment of the safe use of this material and all the cinnamyl
      phenylpropyl materials in fragrances. Belsito, D., Bickers, D., Bruze, M., Dagli,
      M.L., Fryer, A., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A
      toxicologic and dermatologic assessment of cinnamyl phenylpropyl compounds when
      used as fragrance ingredients.

PMID- 21855597
TI  - Solanum torvum Swartz. fruit containing phenolic compounds shows antidiabetic and
      antioxidant effects in streptozotocin induced diabetic rats.
AB  - In this study, quantification of phenolic compounds and the investigation of
      antidiabetic and antioxidant activities of the fruit of Solanum torvum Swartz.
      are described. S. torvum fruit methanol extract (STMe) was administered orally at
      a dose of 200 and 400mg/kg/day to streptozotocin induced diabetic rats for
      30days. The levels of glucose, insulin, total protein, hemoglobin, glycated
      hemoglobin, liver glycogen and marker enzymes of carbohydrate metabolism, hepatic
      function and antioxidants were analyzed. High-performance liquid chromatography
      (HPLC) analysis revealed that STMe contained high levels of phenolic compounds,
      mainly rutin (1.36%w/w), caffeic acid (12.03%w/w), gallic acid (4.78%w/w) and
      catechin (0.46%w/w). STMe at 200 and 400mg/kg reduced blood glucose level by
      17.04% and 42.10%, respectively in diabetic rats. The levels and/or activities of
      other biochemical parameters were restored significantly compared to diabetic
      control rats due to treatment with fruit extract. Histology of liver and pancreas
      in STMe treated groups substantiated the cytoprotective action of the drug.
      Immunohistochemical observation of islets in extract treated diabetic rats showed
      apparent beta-cells regeneration. These findings suggest that S. torvum fruit
      containing phenolic compounds has great potential as a natural source of
      antidiabetic and antioxidant drug.

PMID- 21855598
TI  - Ochratoxin A reduces aflatoxin B1 induced DNA damage detected by the comet assay
      in Hep G2 cells.
AB  - Mycotoxins aflatoxin B1 (AFB1) and ochratoxin A (OTA) can be present together in
      food commodities. These food contaminants are considered to be genotoxins, acting
      by different mechanisms. The aim of this work was to characterize combined
      genotoxic in vitro effects of both mycotoxins in Hep G2 cells. For this purpose,
      cytotoxicity was first determined in isolated and combined treatments in order to
      determine the dose range of genotoxicity studies. Co-exposure of cells to
      OTA+AFB1 for 24 h resulted in additive effects. Genotoxicity was determined in
      Hep G2 cells by the modified comet assay with restriction enzymes (endo III and
      FPG). Significant reactive oxygen species formation was detected in both single
      and combined treatments. AFB1 was genotoxic after 3 h with external metabolic
      activation (S9 mix) and after 24 h without metabolic activation. Co-exposure to
      OTA significantly decreased DNA damage induced by AFB1, not only in breaks and
      apurinic sites but also in FPG-sensitive sites. The apparent contradiction
      between additive cytotoxic effects and antagonic genotoxic effects may be
      explained if AFB1 and OTA compete for the same CYPs, yielding more ROS but less
      AFB1 adducts.

PMID- 21855599
TI  - Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin
      fed zebrafish have elevation of cholesteryl ester transfer protein activity in
      hypercholesterolemia.
AB  - Although many artificial sweeteners (AS) have safety issues, the AS have been
      widely used in industry. To determine the physiologic effect of AS in the
      presence of hyperlipidemia, zebrafish were fed aspartame or saccharin with a high
      cholesterol diet (HCD). After 12 days, 30% of zebrafish, which consumed aspartame
      and HCD, died with exhibiting swimming defects. The aspartame group had 65%
      survivability, while the control and saccharin groups had 100% survivability.
      Under HCD, the saccharin-fed groups had the highest increase in the serum
      cholesterol level (599 mg/dL). Aspartame-fed group showed a remarkable increase
      in serum glucose (up to 125 mg/dL), which was 58% greater than the increase in
      the HCD alone group. The saccharin and HCD groups had the highest cholesteryl
      ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone
      group had 42% CE-transfer. Histologic analysis revealed that the aspartame and
      HCD groups showed more infiltration of inflammatory cells in the brain and liver
      sections. Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish
      exhibited acute swimming defects with an increase in brain inflammation.
      Saccharin-fed zebrafish had an increased atherogenic serum lipid profile with
      elevation of CETP activity.

PMID- 21855600
TI  - Surface alteration of human tooth enamel subjected to acidic and neutral 30%
      hydrogen peroxide.
AB  - OBJECTIVES: To investigate the effects of acidic and neutral 30% hydrogen
      peroxide (HP) on human tooth enamel in terms of chemical structure, mechanical
      property, surface morphology and tooth colour. METHODS: Twenty-seven human dental
      blocks were obtained from premolars and randomly divided into three groups (n=9):
      Group acidic HP (30% HP, pH~3.6), Group neutral HP (30% HP, pH~7.0) and Group DW
      (distilled water, pH~6.8). Attenuated total reflection-Fourier transform infrared
      spectroscopy (ATR-FTIR), Raman spectroscopy, atomic force microscopy (AFM)
      investigation, microhardness test and colour measurements were carried out before
      and after treatments. ATR-FTIR and Raman spectroscopy were analysed and then the
      carbonate:mineral ratio (C:M), Raman absolute intensity (RAI), Raman relative
      intensity (RRI), and laser-induced fluorescence intensity (FI) were obtained for
      evaluation. RESULTS: The C:M, percentage microhardness and percentage RRI of
      group acidic HP decreased more significantly than those of group neutral HP
      (P=0.02, P=0.001, P<0.001, respectively) and group DW (P=0.01, P=0.008, P<0.001,
      respectively). Whilst group neutral HP and group DW had no statistical difference
      in above terms (P=0.818, P=0.528, P=0.158, respectively). Significant
      morphological alterations were observed in group acidic HP. Group acidic HP and
      neutral HP had no significant difference in percentage FI (P=0.652) and DeltaE
      (P=0.906). CONCLUSIONS: This study suggested that neutral 30% HP had the same
      efficiency in tooth bleaching and it caused less deleterious effects on enamel
      than acidic 30% HP.

PMID- 21855601
TI  - Sympathetic and parasympathetic responses to a core disgust video clip as a
      function of disgust propensity and disgust sensitivity.
AB  - It is generally assumed that disgust is accompanied by increased activation of
      the parasympathetic nervous system (PNS). However, empirical support for the role
      of PNS in disgust is scarce. This study tested whether (i) activation of the PNS
      is indeed involved in disgust and (ii) disgust-induced autonomic activation is
      especially pronounced in individuals with high disgust propensity or enhanced
      disgust sensitivity. Participants (N=60) viewed a 5 min disgust-inducing video
      clip. Participants showed increased parasympathetic activity of both the cardiac
      and the digestive components of the autonomic nervous system (ANS), together with
      increased sympathetic activation of the cardiac system. ANS responses were
      independent of subjective disgust and individuals' habitual disgust propensity or
      sensitivity. Results support the hypothesis that PNS activation is involved in
      disgust. The absence of a relationship between subjective and physiological
      indices of disgust indicates that both types of responses reflect independent
      phenomena.

PMID- 21855602
TI  - Filial versus romantic love: contributions from peripheral and central
      electrophysiology.
AB  - A major problem in recent neuroscience research on the processing of loved
      familiar faces is the absence of evidence concerning the elicitation of a genuine
      positive emotional response (love). These studies have two confounds: familiarity
      and arousal. The present investigation controlled for both factors in female
      university students. Two categories of loved faces were chosen: one with higher
      familiarity but lower emotionality (fathers) and the other with higher
      emotionality but lower familiarity (romantic partners). Unfamiliar and baby faces
      were used as control faces. Central and peripheral electrophysiological measures
      as well as subjective indices of valence, arousal, and dominance were recorded.
      Results support the conclusion that viewing loved familiar faces elicits an
      intense positive emotional reaction that cannot be explained either by
      familiarity or arousal. The differences between romantic and filial love appeared
      in the magnitude of some peripheral and subjective indices of emotionality
      (zygomatic activity, valence, arousal, and dominance), that were higher for
      images of the romantic partners, and one central index of familiarity (the P3
      amplitude), that was higher for images of the fathers.

PMID- 21855603
TI  - Challenging the error-likelihood model with a recognition paradigm: an
      electrophysiological study.
AB  - The error-likelihood model (ELM) postulates that activity of the anterior
      cingulate cortex is not only modulated by the commitment of an error but is
      rather dependent on the perceived ELM within task context. In this event-related
      potential (ERP) study we challenge these assumptions with a word-recognition
      paradigm. While learning phases were constant, ELM was modulated during
      recognition by varying the ratio of old and new words: old and new words had the
      same probability in low-risk sessions and the number of new words was tripled in
      high-risk sessions. Response-locked ERPs of correct yes-responses compared to no
      responses revealed two different components with fronto-central distributions.
      The first negativity (time-range of the error-related negativity) elicited
      differentiations between yes- and no-responses. Yes-responses in high-risk
      compared to low-risk sessions resulted in an enlarged negativity. These results
      support the ELM which states that the activation of the anterior cingulate cortex
      is also modulated by the participant's perceived likelihood to commit an error
      and not the correctness of the response per se.

PMID- 21855604
TI  - Distribution and pharmacological characterization of primate NK-2 tachykinin
      receptor in the central nervous system of the rhesus monkey.
AB  - Tachykinin NK-2 receptor, a cognate receptor for neurokinin A, expressed in the
      brain has been suggested as a new target for the treatment of psychiatric
      disorders. In rodents, treatment with NK-2 receptor agonists causes anxiogenic
      effects, while NK-2 receptor antagonists show anxiolytic and antidepressant-like
      effects. However, information about the distribution and functions of NK-2
      receptors in the central nervous system (CNS) in primates is still lacking. Here,
      we examined the distribution and pharmacological profile of NK-2 receptors in the
      rhesus monkey (Macaca mulatta) to clarify the molecular basis of NK-2-mediated
      tachykininergic functions in the primate CNS. NK-2 receptors cloned from the
      rhesus monkey brain showed similar pharmacological properties to those of human
      NK-2 receptors. Substantial expression levels of NK-2 mRNA were observed in all
      the brain regions examined, including areas pertinent to the emotional networks
      such as the prefrontal cortex, cingulate cortex and amygdala. These findings
      suggest that NK-2 receptors may play important roles in the pathophysiology of
      psychiatric disorders.

PMID- 21855605
TI  - Curcumin ((E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione)
      activates and desensitizes the nociceptor ion channel TRPA1.
AB  - The ion channel TRPA1 is activated by a wide variety of noxious stimuli, such as
      pollutants, products of oxidative tissue damage, and pungent natural products.
      Many TRPA1 activators are reactive electrophiles that form Michael adducts with
      cysteine and lysine residues of TRPA1's intracellular N-terminus. Curcumin, the
      active principle of turmeric root (Curcuma longa), can also form Michael adducts.
      In order to test the hypothesis that the electrophilic curcumin activates TRPA1,
      we have performed whole-cell, voltage-clamp analysis on both HEK293 cells
      expressing human TRPA1 (hTRPA1-HEK) and native mouse vagal neurons. In nominally
      calcium-free extracellular and intracellular solutions which minimized the
      chances of calcium-dependent activation of TRPA1, curcumin increased TRPA1
      currents in hTRPA1-HEK cells in a concentration-dependent manner (1-30MUM) but
      did not cause block or activation of recombinant TRPM8 and TRPV1. In addition, 7
      out of 11 vagal sensory neurons from wild type mice responded to curcumin (30MUM)
      with inward currents (11.6+/-5.4pA/pF) that were largely reversed by TRPA1
      blockers. In marked contrast, neurons from TRPA1-deficient mice did not respond
      to curcumin (30MUM). With physiological levels of calcium added to the external
      solution to facilitate channel desensitization, curcumin-dependent currents in
      hTRPA1-HEK cells were completely desensitized and exhibited marked tachyphylaxis
      upon subsequent application of curcumin. Taken together, these results
      demonstrate that curcumin causes activation and subsequent desensitization of
      native and recombinant TRPA1 ion channels of multiple mammalian species.

PMID- 21855606
TI  - Morphological transformation and proliferation of rat astrocytes as induced by
      sulfated polysaccharides from the sea cucumber Stichopus japonicus.
AB  - In this report, we demonstrate that the sulfated polysaccharide, Haishen (HS),
      which was isolated from the body wall of the sea cucumber Stichopus japonicus can
      induce morphological transformation and proliferation of astrocytes in vitro when
      combined with basic fibroblast growth factor 2 (FGF-2). Cell morphology showed no
      change when induced by HS or FGF-2 alone. However, combinational treatment of HS
      and FGF-2 promoted transformation of normal astrocyte into a stella morphology
      (stellation), along with an increase in the expression and rearrangement of glial
      fibrillary acidic protein (GFAP). Further analysis of HS- and FGF-2-treated cells
      indicated a reduced percentage of cells in the G0/G1 phase, whereas the cell
      proliferation index (S phase) was increased. The proportion of 5-bromo-2
      deoxyuridine (BrdU)-positive cells increased in response to the combination of HS
      and FGF-2. With respect to cell cycle signaling, immunoblotting assay
      demonstrated an accumulation of Cyclin D1. These observations suggest that HS may
      play a role in astrocyte morphological transformation and proliferation, and this
      activation requires a synergism with FGF-2.

PMID- 21855607
TI  - Pyruvate therapy for mitochondrial DNA depletion syndrome.
AB  - BACKGROUND: Mitochondrial DNA depletion syndromes are a group of heterogeneous
      autosomal recessive disorders associated with a severe reduction in mitochondrial
      DNA in the affected tissues. Sodium pyruvate has been reported to have a
      therapeutic effect in mitochondrial diseases. METHODS: We analyzed the effects of
      0.5g/kg of sodium pyruvate administered through a nasogastric tube in a one-year
      old patient with myopathic mitochondrial DNA depletion syndrome. To evaluate the
      improvement, we used the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS)
      and manual muscle testing. As the improvement of motor functions in this severely
      disabled infant could not be comprehensively detected by NPMDS, we also observed
      the infant's ability to perform several tasks such as pouting, winking, and
      number of times she could tap a toy xylophone with a stick. Blood lactate and
      pyruvate levels were also monitored. RESULTS: After one month's treatment, the
      NPMDS score in section IV, the domain for the quality of life, improved from 17
      to13. The infant became capable of raising her forearm, lower leg and wrist
      against gravity. The maximum number of times she could repeat each task increased
      and the movements became brisker and stronger. No significant change of the blood
      lactate level or lactate-to-pyruvate ratio, both of which were mildly increased
      at the initiation of the therapy, was observed despite the clinical improvement.
      CONCLUSION: Sodium pyruvate administered at 0.5g/kg improved the muscle strength
      and the NPMDS score of an infant with myopathic mitochondrial DNA depletion
      syndrome. GENERAL SIGNIFICANCE: Sodium pyruvate may be effective for ameliorating
      the clinical manifestations of mitochondrial diseases. This article is part of a
      Special Issue entitled: Biochemistry of Mitochondria.

PMID- 21855608
TI  - Non-transferrin bound iron: a key role in iron overload and iron toxicity.
AB  - BACKGROUND: Besides transferrin iron, which represents the normal form of
      circulating iron, non-transferrin bound iron (NTBI) has been identified in the
      plasma of patients with various pathological conditions in which transferrin
      saturation is significantly elevated. SCOPE OF THE REVIEW: To show that: i) NTBI
      is present not only during chronic iron overload disorders (hemochromatosis,
      transfusional iron overload) but also in miscellaneous diseases which are not
      primarily iron overloaded conditions; ii) this iron species represents a
      potentially toxic iron form due to its high propensity to induce reactive oxygen
      species and is responsible for cellular damage not only at the plasma membrane
      level but also towards different intracellular organelles; iii) the NTBI concept
      may be expanded to include intracytosolic iron forms which are not linked to
      ferritin, the major storage protein which exerts, at the cellular level, the same
      type of protective effect towards the intracellular environment as transferrin in
      the plasma. MAJOR CONCLUSIONS: Plasma NTBI and especially labile plasma iron
      determinations represent a new important biological tool since elimination of
      this toxic iron species is a major therapeutic goal. GENERAL SIGNIFICANCE: The
      NTBI approach represents an important mechanistic concept for explaining cellular
      iron excess and toxicity and provides new important biochemical diagnostic tools.
      This article is part of a Special Issue entitled Transferrins: Molecular
      mechanisms of iron transport and disorders.

PMID- 21855609
TI  - X-ray structures of transferrins and related proteins.
AB  - BACKGROUND: Transferrins are a group of iron-binding proteins including serum
      transferrin, lactoferrin and ovotransferrin. SCOPE OF REVIEW: The structures of
      transferrins are discussed. GENERAL SIGNIFICANCE: The typical transferrin
      molecules are folded into two homologous lobes. X-ray crystallography revealed
      that each lobe is further divided into two similarly sized domains, and that an
      iron-binding site is contained within the inter-domain cleft. The six iron
      coordination sites are occupied by four residues and a bidentate carbonate anion.
      MAJOR CONCLUSIONS: The structures of the apo- and holo-forms revealed that the
      transferrins undergo a large-scale conformational change upon the uptake and
      release of irons: domains rotate as rigid bodies around a screw axis passing
      through inter-domain contacts. The iron-release mechanism of transferrin N-lobe
      is also revealed by X-ray crystallography; two basic residues in two domains form
      an unusual hydrogen bond in neutral pH, and the bond should be broken and
      facilitate iron release at a low pH of the endosome. For ovotransferrin, the iron
      release kinetics of two lobes correspond well with the numbers of anion binding
      sites found in crystal structures. The structures of transferrins bound to other
      metals revealed that the flexibility of the transferrin structure allows the
      ability to bind to other metals. This article is part of a Special Issue entitled
      Transferrins: Molecular mechanisms of iron transport and disorders.

PMID- 21855610
TI  - Colorectal cancers choosing sides.
AB  - In contrast to the majority of sporadic colorectal cancer which predominantly
      occur in the distal colon, most mismatch repair deficient tumours arise at the
      proximal side. At present, these regional preferences have not been explained
      properly. Recently, we have screened colorectal tumours for mutations in Wnt
      related genes focusing specifically on colorectal location. Combining this
      analysis with published data, we propose a mechanism underlying the side-related
      preferences of colorectal cancers, based on the specific acquired genetic defects
      in beta-catenin signalling.

PMID- 21855611
TI  - The influence of matching degrees of synchronous auditory and visual information
      in videos of real-world events on cognitive integration: an event-related
      potential study.
AB  - In this article, we aim to study the influence of matching degrees of synchronous
      natural auditory and visual information on cognitive integration. Videos with
      matched, moderately matched, and mismatched audio-visual information were used as
      stimuli. The results showed that videos with moderately matched audio-visual
      information could elicit N400, P600, and late negativity (LN) effects, while
      videos with mismatched audio-visual information could elicit N400 and late
      negativity effects as compared with those with matched audio-visual information.
      It was further proven that N400 might reflect the connection process during
      multisensory integration, and P600 was more related to the evaluation process on
      the matching degrees of the audio-visual information in videos. Late negativity
      under the mismatched condition might be the combination of late frontal
      negativity (LFN) and late posterior negativity (LPN), which reflected the
      attention reallocating process and the recognition process, while late negativity
      under the moderately matched condition might be the LPN, which was related to the
      recognition process in the human brain. It was demonstrated that cognitive
      integration of synchronous audio-visual information would be modulated by
      different matching degrees of audio-visual information as indexed by different
      event-related potential (ERP) effects.

PMID- 21855612
TI  - Ameliorative effect of N-desmethylclozapine in animal models of social deficits
      and cognitive functions.
AB  - One of the major circulating metabolites of clozapine, N-desmethylclozapine
      (NDMC), has been demonstrated to exhibit partial agonistic activity at M(1)
      muscarinic receptors. Some of the unique therapeutic effects of clozapine might
      involve the pharmacological effects of this metabolite. The purpose of the
      present study was therefore to examine whether NDMC improved behavioral
      abnormalities in animal models of social deficits and cognitive deficits of
      schizophrenia. NDMC (3mg/kg) and clozapine (1-3mg/kg) each improved the reduction
      of social interaction caused by a non-competitive N-methyl-d-aspartate (NMDA)
      receptor antagonist, 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10-imine (MK-801) (0.1mg/kg), without affecting locomotor activity in rats.
      NDMC (3-10mg/kg) and clozapine (1-3mg/kg) each also resulted in better
      discrimination of a novel from a familiar object 24h after a training trial in a
      rat object recognition test. These findings suggest that NDMC can improve
      behavior in animal models of social deficits and cognitive deficits of
      schizophrenia as well as clozapine.

PMID- 21855614
TI  - Gaze direction - a cue for hidden food in rooks (Corvus frugilegus)?
AB  - Other individual's head- and eye-directions can be used as social cues indicating
      the presence of important events. Among birds, ravens and rooks have been shown
      to co-orient with conspecifics and with humans by following their gaze direction
      into distant space and behind visual screens. Both species use screens to cache
      food in private; also, it had been suggested that they may rely on gaze cues to
      detect hidden food. However, in an object-choice task, ravens failed to do so,
      and their competitive lifestyle may have prevented them from relying on these
      cues. Here we tested closely related and cooperative rooks. Food was hidden in
      one of two cups and the experimenter gazed at the baited cup. In a second
      experiment, we aimed to increase the birds' motivation to choose correctly by
      increasing the investment needed to obtain the reward. To do so, the birds had to
      pull on a string to obtain the cup. Here, the birds as a group tended to rely on
      gaze cues. In addition, individual birds quickly learned to use the cue in both
      experiments. Although rooks may not use gaze cues to find hidden food
      spontaneously, they may quickly learn to do so.

PMID- 21855615
TI  - Additional box B of RNA polymerase III promoter in SINE B1 can be functional.
AB  - Many genes of small RNAs and short interspersed elements (SINEs) are transcribed
      by RNA polymerase III due to an internal promoter that is composed of two boxes
      (A and B) spaced by 30-45bp. Rodent SINE B1 originated from 7SL RNA, and a 29-bp
      tandem duplication took place in B1 at an early stage of its evolution. As a
      result of this duplication, an additional box B (named B') located at a distance
      of 79-82bp from box A arose in SINE B1. Here we have shown that despite the
      unusually large distance between boxes A and B', they can form an active
      promoter. In chinchillas, guinea pigs, and other rodents belonging to clade
      Ctenohystrica, structure of the B' box was well preserved and closely resembles
      the canonical B box. One may suggest therefore, that box B' can functionally
      replace box B in those copies of B1 where the latter has lost activity due to
      mutations.

PMID- 21855613
TI  - Genetically engineered mouse models shed new light on the pathogenesis of
      neurofibromatosis type I-related neoplasms of the peripheral nervous system.
AB  - Neurofibromatosis type 1 (NF1), the most common genetic disorder affecting the
      human nervous system, is characterized by the development of multiple benign
      Schwann cell tumors in skin and large peripheral nerves. These neoplasms, which
      are termed dermal and plexiform neurofibromas respectively, have distinct
      clinical courses; of particular note, plexiform, but not dermal, neurofibromas
      often undergo malignant progression to form malignant peripheral nerve sheath
      tumors (MPNSTs), the most common malignancy occurring in NF1 patients. In recent
      years, a number of genetically engineered mouse models have been created to
      investigate the molecular mechanisms driving the pathogenesis of these tumors.
      These models have been designed to address key questions including: (1) whether
      NF1 loss in the Schwann cell lineage is essential for tumorigenesis; (2) what
      cell type(s) in the Schwann cell lineage gives rise to dermal neurofibromas,
      plexiform neurofibromas and MPNSTs; (3) how the tumor microenvironment
      contributes to neoplasia; (4) what additional mutations contribute to
      neurofibroma-MPNST progression; (5) what role different neurofibromin-regulated
      Ras proteins play in this process and (6) how dysregulated growth factor
      signaling facilitates PNS tumorigenesis. In this review, we summarize the major
      findings from each of these models and their limitations as well as how
      discrepancies between these models may be reconciled. We also discuss how
      information gleaned from these models can be synthesized to into a comprehensive
      model of tumor formation in peripheral nervous system and consider several of the
      major questions that remain unanswered about this process.

PMID- 21855616
TI  - Rutile TiO2 particles exert size and surface coating dependent retention and
      lesions on the murine brain.
AB  - The rising commercial use and large-scale production of engineered nanoparticles
      (NPs) may lead to unintended exposure to humans. The central nervous system (CNS)
      is a potential susceptible target of the inhaled NPs, but so far the amount of
      studies on this aspect is limited. Here, we focus on the potential neurological
      lesion in the brain induced by the intranasally instilled titanium dioxide (TiO2)
      particles in rutile phase and of various sizes and surface coatings. Female mice
      were intranasally instilled with four different types of TiO2 particles (i.e. two
      types of hydrophobic particles in micro- and nano-sized without coating and two
      types of water-soluble hydrophilic nano-sized particles with silica surface
      coating) every other day for 30 days. Inductively coupled plasma mass
      spectrometry (ICP-MS) were used to determine the titanium contents in the sub
      brain regions. Then, the pathological examination of brain tissues and
      measurements of the monoamine neurotransmitter levels in the sub-brain regions
      were performed. We found significant up-regulation of Ti contents in the cerebral
      cortex and striatum after intranasal instillation of hydrophilic TiO2 NPs.
      Moreover, TiO2 NPs exposure, in particular the hydrophilic NPs, caused obvious
      morphological changes of neurons in the cerebral cortex and significant
      disturbance of the monoamine neurotransmitter levels in the sub-brain regions
      studied. Thus, our results indicate that the surface modification of the NPs
      plays an important role on their effects on the brain. In addition, the
      difference in neurotoxicity of the two types of hydrophilic NPs may be induced by
      the shape differences of the materials. The present results suggest that
      physicochemical properties like size, shape and surface modification of the
      nanomaterials should be considered when evaluating their neurological effects.

PMID- 21855617
TI  - Targeted liposomes to deliver DNA to cells expressing 5-HT receptors.
AB  - Cell targeted delivery of drugs, including nucleic acids, is known to enhance the
      therapeutic potential of free drugs. We used serotonin (5-HT) as the targeting
      ligand to deliver plasmid DNA to cells specifically expressing 5-HT receptor. Our
      liposomal formulation includes the 5-HT conjugated targeting lipid, a cationic
      lipid and cholesterol. DNA-binding studies indicate that the targeting 5-HT-lipid
      binds DNA efficiently. The formulation was tested and found to efficiently
      deliver DNA into CHO cells stably expressing the human serotonin(1A) receptor
      (CHO-5-HT(1A)R) compared to control CHO cells. Liposomes without the 5-HT moiety
      were less efficient in both cell lines. Similar enhancement in transfection
      efficiency was also observed in human neuroblastoma IMR32 and hepatocellular
      carcinoma (HepG2) cells. Cell uptake studies using CHO-5-HT(1A)R cells by flow
      cytometry and confocal microscopy clearly indicated that the targeting liposomes
      through 5-HT moiety may have a direct role in increasing the cellular uptake of
      DNA-lipid complexes. To our knowledge this is the first report that demonstrates
      receptor-targeted nucleic acid delivery into cells expressing 5-HT receptor.

PMID- 21855618
TI  - Sufficiency of a single administration of filarial antigens adsorbed on polymeric
      lamellar substrate particles of poly (L-lactide) for immunization.
AB  - A majority of antigens require repeated administration to ensure development of
      adequate humoral and cell mediated immune response. To minimize the number of
      administrations required, we investigated the utility of biodegradable polymeric
      lamellar substrate particles of poly (l-lactide) (PLSP) as adjuvant for filarial
      antigen preparations. PLSP was prepared and characterized and Brugia malayi adult
      worm extract (BmA) and its SDS-PAGE resolved 54-68 kDa fraction F6 were adsorbed
      on to PLSP. Swiss mice received a single injection of PLSP-F6, PLSP-BmA, FCA-F6,
      FCA-BmA and two doses of the plain antigens. Specific IgG, IgG1, IgG2a, IgG2b and
      IgE levels in serum, IFN-gamma, TNF-alpha and nitric oxide (NO) release from
      cells of the immunized animals in response to antigen challenge were studied. The
      average size of PLSP particles was <10 MUm and its % antigen adsorption efficacy
      was 60.4, 55.2 and 61.6 for BSA, BmA and F6, respectively. Single injection of
      PLSP-F6 or PLSP-BmA produced better immune responses compared to one injection of
      FCA-F6/BmA or two injections of plain F6 or BmA. Moreover, PLSP-F6 produced much
      better response than PLSP-BmA. These data demonstrate for the first time that
      PLSP is a superior immunoadjuvant for enhancing the immune response to filarial
      BmA and F6 molecules and obviates the need for multiple immunization injections.

PMID- 21855619
TI  - Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis,
      inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by
      inducing the expression of maspin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine Scutellaria
      baicalensis is prescribed for the treatment of a variety of inflammatory diseases
      and tumors in clinic in China. However, the detailed mechanism of anti-metastasis
      effect of wogonin, a main active ingredient of Scutellaria baicalensis, remains
      elusive. AIM OF THE STUDY: The present study was designed to investigate the
      action and mechanism of wogonin on the mobility and invasion of human gallbladder
      carcinoma GBC-SD cells. MATERIALS AND METHODS: Viability, apoptosis, mRNA and
      protein expression of tumor cells were analyzed by MTT, Annexin V staining, real
      time PCR and Western blot, respectively. The migration and invasion assay was
      used to evaluate the anti-metastasis effect of wogonin. Knockdown of maspin was
      performed by specific small interference RNA. RESULTS: Wogonin at the dose of 1
      10 MUM, which did not induce apoptosis, significantly inhibited the mobility and
      invasion activity of human gallbladder carcinoma GBC-SD cells. In addition, the
      expressions of matrix metalloproteinase (MMP)-2, MMP-9 and phosphorylated
      extracellular regulated protein kinase 1/2 (ERK1/2) but not phosphorylated Akt
      were dramatically suppressed by wogonin in a concentration-dependent manner.
      Furthermore, the metastasis suppressor maspin was confirmed as the downstream
      target of wogonin. Both maspin mRNA and protein were upregulated by wogonin.
      Interestingly, the knockdown of maspin resulted in almost completely blocking of
      wogonin-induced inhibition of MMP-2, MMP-9 and phosphorylated ERK1/2 as well as
      the mobility and invasion activity of GBC-SD cells. CONCLUSIONS: These findings
      suggest that wogonin inhibits cell mobility and invasion by upregulating the
      metastasis suppressor maspin. Together, these data provide novel insights into
      the chemoprotective effect of wogonin, a main active ingredient of Chinese
      medicine Scutellaria baicalensis.

PMID- 21855620
TI  - Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei
      Rhizoma in rats.
AB  - AIM OF THE STUDY: Rhei Rhizoma, the rhizome of Rheum palmatum L. (RP), is a
      popular herb in clinical Chinese medicine. RP is abundant in polyphenolic
      anthraquinones, which have been reported to show various beneficial
      bioactivities. This study investigated the pharmacokinetics and tissue
      distribution of anthraquinones following seven-dose administration of RP
      decoction to rats. MATERIALS AND METHODS: Six Sprague-Dawley rats were given 2.0
      g/kg of RP twice daily for seven doses and blood samples were collected at
      designated time after the 7th dose. Another six rats were sacrificed at 30 min
      after the 7th dose and organs including liver, kidney, lung and brain were
      collected. Serum and tissue specimens were assayed by HPLC before and after
      hydrolysis with beta-glucuronidase and sulfatase, respectively. RESULTS:
      Pharmacokinetic analysis indicated that the anthraquinones in serum mainly
      presented as glucuronides/sulfates and contained higher ratio of sulfates when
      compared with single-dose administration of RP. Contrary to the finding in serum,
      tissue analysis discovered mainly free form of anthraquinone in most organs
      assayed, such as aloe-emodin and rhein in kidney, liver, lung; emodin in liver,
      lung; trace of chrysophanol in kidney and liver. In all brains, neither free
      forms nor their glucuronides/sulfates have been detected. CONCLUSIONS: The
      glucuronides/sulfates of anthraquinones were the major forms in bloodstream,
      whereas the free forms of most anthraquinones were predominant in kidney and
      liver.

PMID- 21855621
TI  - The analgesic and anti-rheumatic effects of Thladiantha dubia fruit crude
      polysaccharide fraction in mice and rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Thladiantha dubia has been used in
      Chinese manchu nationality folk medicine for treatment of various pains, such as
      rheumatic pain, lumbocrural pain, and dysmenorrhea. The aim of the present study
      was to evaluate the anti-rheumatic effect of Thladiantha dubia fruit crude
      polysaccharide (TF-P) fraction in rats. MATERIALS AND METHODS: TF-P was evaluated
      in mice for analgesic activity using acetic acid-induced abdominal contractions
      test and for anti-inflammatory activity using xylene-induced ear oedema model.
      Moreover, rheumatoid arthritis (RA) was induced by injection of CFA into the
      subplantar surface of the hind paw of the male Wistar rats. Joint swelling was
      measured. In order to evaluate the effect of TF-P on disease progression,
      proinflammatory mediators (TNF-alpha and IL-2), and antioxidant indicators (SOD,
      MDA, and NO) were determined in rats induced by CFA. Pathologic changes of RA in
      rats were also observed under light microscope. RESULTS AND CONCLUSIONS: In the
      present study, TF-P at the dose of 200mg/kg (according to the clinical
      traditional dosage) significantly reduced writhings and stretchings induced by
      the acetic acid in mice. TF-P significantly inhibited xylene-induced ear oedema
      in mice, compared with control group. TF-P significantly inhibited inoculated and
      non-inoculated joint swellings in rats induced by CFA. TF-P had no effect of body
      weight in rats. The histopathological analysis suggested that TF-P obviously
      alleviated the degree of RA rats. TF-P treated rats preserved a nearly normal
      histological architecture of the joint. Results of the present study confirm the
      use of Thladiantha dubia traditionally for the treatment of painful and
      inflammatory conditions. Those results suggest TF-P has protective and
      therapeutic effects on RA rats induced by CFA.

PMID- 21855622
TI  - The anti-hypertensive effect of Danshen (Salvia miltiorrhiza) and Gegen (Pueraria
      lobata) formula in rats and its underlying mechanisms of vasorelaxation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae (Danshen) and Radix
      Puerariae lobatae (Gegen) have long been used in traditional Chinese Medicine and
      serve as the principal herbs in treating cardiovascular disease. AIMS OF THE
      STUDY: In the present study, an aqueous extract comprising Danshen and Gegen in
      the ratio of 7:3 (DG) was investigated for its anti-hypertension in vivo and
      vasodilative activities ex vivo. MATERIALS AND METHODS: The anti-hypertensive
      effect of DG extract was investigated in spontaneously hypertensive rat (SHR) by
      measuring systolic blood pressure (SBP). Oral administration of DG extract was
      started at age of 6 weeks and 14 weeks for the preventive and therapeutic
      studies, respectively. Blood pressure was measured by tail-cuff method biweekly
      for 12 weeks. The ex vivo vasodilative activities of DG extract, its dependency
      on endothelium and the involvement of nitric oxide, prostacyclin and potassium
      channels were investigated using isolated rat aorta ring in organ bath. RESULTS:
      For in vivo study, systolic blood pressure was significantly reduced in DG
      extract-treated groups (90.2 and 300 mg/kg) as compared with the SHR control in
      both preventive and therapeutic studies. However, DG extract was unable to
      suppress or delay the onset of hypertension in the preventive study. For ex vivo
      study, the results showed that DG extract induced a concentration-dependent
      relaxation in aorta and persisted response was observed with the removal of
      endothelium. Besides, pretreatment with a non-selective potassium channel
      inhibitor tetraethylammonium (TEA) also significantly inhibited DG extract
      induced vasodilation. Further investigations on specific potassium channel
      blockers revealed that ATP-sensitive potassium (K(ATP)) channel inhibitor
      glibenclamide, inward rectifier potassium (Kir) inhibitor barium chloride and
      voltage-dependent potassium (K(v)) channel inhibitor 4-aminopyridine, but not
      BK(Ca) channel inhibitor iberiotoxin, exerted significant inhibition on DG
      extract-induced vasodilation. CONCLUSIONS: The results of in vivo SHR animal
      model suggested that DG aqueous extract possessed blood pressure lowering effect
      on both pre- and post-hypertensive rats, which could be explained by its
      endothelium-independent vasodilation via the opening of K(ATP), Kir and K(v)
      channels.

PMID- 21855623
TI  - Influences of Fructus evodiae pretreatment on the pharmacokinetics of Rhizoma
      coptidis alkaloids.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma coptidis is a traditional Chinese
      medicine with pharmacological properties. It is usually prescribed with Fructus
      evodiae as traditional Chinese medicine (TCM) formulas. Here we report the
      influences of Fructus evodiae on the pharmacokinetics of the Rhizoma coptidis
      alkaloids and propose possible mechanisms. MATERIALS AND METHODS: Pharmacokinetic
      experiments were performed in rats. In vitro absorption experiments were
      performed in everted rat gut sacs, while in vitro metabolism experiments and
      determination of hepatic UDP-glucuronosyltransferase (UGT) 1A1 mRNA expression
      were performed in rat liver microsomes. RESULTS: Pretreatment with Fructus
      evodiae extract for two weeks decreased the systemic exposure of the Rhizoma
      coptidis alkaloids. This effect was not due to inhibition of absorption or
      enhanced hepatic phase I metabolism of the Rhizoma coptidis alkaloids. However,
      Fructus evodiae pretreatment enhanced both the activity and expression of hepatic
      UGT1A1. CONCLUSIONS: The results showed that Fructus evodiae pretreatment
      decreased the systemic exposure of the Rhizoma coptidis alkaloids by inducing
      hepatic UGT1A1.

PMID- 21855624
TI  - Isolation of gentiopicroside from Gentianae Radix and its pharmacokinetics on
      liver ischemia/reperfusion rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gentiopicroside (GPS) is a secoiridoid glucoside
      isolated from the ethanol extract of Gentianae Radix with a content of 13%, which
      has been used for centuries in Chinese as a digestive aid. AIM OF THE STUDY: This
      study investigates the pharmacokinetics of GPS and its metabolic pathway for the
      liver ischemia/reperfusion (I/R) in rats. MATERIALS AND METHODS: The experimental
      animals were anesthetized intraperitoneally (i.p.) with a mixture of urethane
      (1.0 g/kg) and alpha-chloralose (0.1 g/kg). A midline laparatomy was performed
      and the liver hilum was gently exposed. All structures in the portal triad
      (hepatic artery, portal vein, and bile duct) to the left and median liver lobes
      were occluded with silk thread for 30 min. Ischemia was followed by a sudden
      reperfusion after removing the occluding threads. After 60 min reperfusion, the
      rats received a single intravenous 5 mg/kg dose of GPS. RESULTS: The area under
      concentration curve (AUC) was significantly increased; however, the clearance
      (Cl) was significantly decreased in the liver I/R rats. Furthermore, after
      pretreated with SKF-525A (50 mg/kg, i.p.), a cytochrome P450 (CYP) inhibitor,
      AUC, elimination half-life (t(1/2)) and the mean residence time (MRT) of GPS in
      rat blood were significantly increased, suggesting that CYP was involved in the
      metabolism of GPS. For the group without liver I/R, GPS was administered at doses
      of 5 mg/kg and 100 mg/kg intravenously and orally, respectively. The
      pharmacokinetic results indicated that the AUC was 565+/-95.1 and 1163+/-273 min
      MUg/mL and the t(1/2) of GPS was 71+/-9 and 106+/-17 min after intravenous and
      oral administration, respectively. The oral bioavailability of GPS was 10.3+/
      2.4% in the rats. CONCLUSIONS: The status of I/R might prolong the disposition of
      GPS, and the plasma concentration of GPS in the liver I/R injury rats was
      significantly increased. The increased body exposure of GPS in the treatment of
      liver I/R may result from the decreased metabolism of GPS mediated by CYP in the
      liver.

PMID- 21855625
TI  - Almost total protection from age-related macular degeneration by haplotypes of
      the Regulators of Complement Activation.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in
      developed countries. It has been proposed that the polymorphism encoding Y402H
      (T1277C) in the complement factor H gene (CFH) is one of the main determinants of
      disease. We genotyped the polymorphism at a number of loci in the region
      encompassing the Regulators of Complement Activation (RCA) on chromosome 1,
      including T1277C SNP, in 187 patients and 146 controls. Haplotypes have been
      classified as protective (P) or susceptible (S) with respect to AMD. This
      included the identification of an S haplotype with a T at 1277. The results show
      that no single locus should be assumed to be directly responsible for AMD, but
      rather argue for the existence of RCA haplotypes, which can be assigned
      meaningful predictive values for AMD. We conclude that the critical sequences are
      within a region 450 kb centromeric to 128 kb telomeric of CFH.

PMID- 21855626
TI  - The beta2-adrenergic receptor on T and B lymphocytes: do we understand it yet?
AB  - The role played by the beta2-adrenergic receptor (beta(2)AR) in regulating the
      level of T and B lymphocyte function has been studied for over half a century.
      During this time, we have learned that T and B lymphocytes express almost
      exclusively the beta(2)AR, and that the level of expression on a specific
      lymphocyte subset differs due to epigenetic regulation by histone and DNA
      methylation. We have also learned that engagement of the beta(2)AR on
      lymphocytes, by either norepinephrine or a selective pharmacologic ligand,
      regulates the level of lymphocyte activity differentially, depending on the time
      of receptor engagement in relation to the activation and differentiation state of
      the cell, the molecular signaling pathway activated, and the cytokine
      microenvironment. The challenge now is to determine if we understand enough about
      how this receptor functions on lymphocytes to predict the relevance of such
      regulation to overall immune homeostasis and the development/progression of human
      disease.

PMID- 21855627
TI  - c-Fos expression after deep brain stimulation of the pedunculopontine tegmental
      nucleus in the rat 6-hydroxydopamine Parkinson model.
AB  - Deep brain stimulation (DBS) is used to alleviate motor dysfunction in
      Parkinson's disease (PD). The pedunculopontine nucleus (PPN) may be a potential
      target for severe freezing and postural instability with 25 Hz stimulation being
      considered more effective than 130 Hz stimulation. Here we evaluated the
      expression of c-Fos after 25 Hz and 130 Hz DBS of the pedunculopontine tegmental
      nucleus (PPTg, i.e., the rodent equivalent to the human PPN) in the rat 6
      hydroxydopamine (6-OHDA) PD model. Anaesthetized male Sprague Dawley rats with
      unilateral 6-OHDA-induced nigrostriatal lesions were stimulated with 25 Hz, 130
      Hz, or 0 Hz sham-stimulation for 4h by electrodes implanted into the ipsilateral
      PPTg. Thereafter the distribution and number of neurons expressing the immediate
      early gene c-Fos, a marker for acute neuronal activity, was assessed. DBS of the
      PPTg induced strong ipsilateral c-Fos expression at the stimulation site, with 25
      Hz having a more marked impact than 130 Hz. Additionally, c-Fos was strongly
      expressed in the central gray. In the dorsal part expression was stronger after
      25 Hz stimulation, while in the medial and ventral part there was no difference
      between 25 Hz and 130 Hz stimulation. Expression in the basal ganglia was
      negligible. In the rat 6-OHDA PD model stimulation of the PPTg did not affect c
      Fos expression in the basal ganglia, but had a strong impact on other functional
      circuitries. PPN stimulation in humans might therefore also have an impact on
      other systems than the motor system.

PMID- 21855628
TI  - HIV-1 Tat increases oxidant burden in the lungs of transgenic mice.
AB  - Chronic human immunodeficiency virus infection is associated with higher
      incidence of pulmonary complications including hypertension, vasculopathy,
      lymphocytic alveolitis, and interstitial pneumonitis not attributed to either
      opportunistic infections or presence of the virus. The Tat (transactivator of
      transcription) protein, a required transactivator for expression of full-length
      viral genes, is pleiotropic and influences expression of cellular inflammatory
      genes. Tat-dependent transactivation of cellular genes requires specific
      mediators, including NF-kappaB, widely recognized as sensitive to changes in
      cellular oxidant burden. We hypothesized that overproduction of Tat leads to
      increased oxidant burden and to alterations in basal inflammatory status as
      measured by NF-kappaB activation. We engineered transgenic mouse lines that
      express Tat (86-amino-acid isoform) in the lung under the control of the
      surfactant protein C promoter. Tat-transgenic mice exhibit increased pulmonary
      cellular infiltration, increased nitrotyrosine and carbonyl protein
      modifications, and increased levels of NF-kappaB, MnSOD, and thioredoxin
      interacting protein. These data indicate that Tat increases oxidant burden and
      resets the threshold for inflammation, which may increase susceptibility to
      secondary injuries.

PMID- 21855629
TI  - A novel small molecule deubiquitinase inhibitor blocks Jak2 signaling through
      Jak2 ubiquitination.
AB  - AG490 is a tyrosine kinase inhibitor with activity against Jak2 and apoptotic
      activity in specific leukemias. Due to its weak kinase inhibitory activity and
      poor pharmacology, we conducted a cell-based screen for derivatives with improved
      Jak2 inhibition and activity in animals. Two hits emerged from an initial small
      chemical library screen, and more detailed structure-activity relationship
      studies led to the development of WP1130 with 50-fold greater activity in
      suppressing Jak2-dependent cytokine signaling than AG490. However, WP1130 did not
      directly suppress Jak2 kinase activity, but mediated Jak2 ubiquitination
      resulting in its trafficking through HDAC6 to perinuclear aggresomes without
      cytokine stimulation or SOCS-1 induction. Jak2 primarily contained K63-linked
      ubiquitin polymers, and mutation of this lysine blocked Jak2 ubiquitination and
      mobilization in WP1130-treated cells. Further analysis demonstrated that WP1130,
      but not AG490, acts as a deubiquitinating enzyme (DUB) inhibitor, possibly
      through a Michael addition reaction. We conclude that chemical modification of
      AG490 resulted in development of a DUB inhibitor with activity against a DUB
      capable of modulating Jak2 ubiquitination, trafficking and signal transduction.

PMID- 21855630
TI  - MMP-9 silencing regulates hTERT expression via beta1 integrin-mediated FAK
      signaling and induces senescence in glioma xenograft cells.
AB  - In more than 90% of cancers including glioma, telomere elongation reverse
      transcriptase (hTERT) is overexpressed. In the present study, we sought to
      explore whether matrix metalloproteinase-9 (MMP-9) shRNA could alter hTERT
      mediated proliferation in glioma cells. MMP-9 shRNA induced senescence and
      apoptosis in glioma cells by inhibiting hTERT expression and telomere activity.
      MMP-9 silencing decreased oncogenic c-Myc expression (hTERT activator), whereas
      the expression of the c-Myc antagonist MAD increased drastically (hTERT
      repressor); both c-Myc and MAD are transcription factors for hTERT. In addition,
      MMP-9 suppression turns the switch from c-Myc/MAX to MAD/MAX heterodimer binding
      to the hTERT promoter as determined by chromatin immunoprecipitation assay. We
      also show that silencing MAD via siRNA restored hTERT expression and inhibited
      senescence in glioma cells. MMP-9 transcriptional suppression decreased the
      expression of FAK, phospho FAK and beta1 integrin in glioma xenograft cells.
      Further, MMP-9 suppression decreased the interaction of beta1 integrin/FAK and
      also MMP-9/beta1 integrin as confirmed by immunoprecipitation analysis. Studies
      with either function blocking beta1 integrin or FAK shRNA indicate that
      suppression of MMP-9 decreased beta1 integrin-mediated induction of FAK, which
      led to decreased hTERT expression. Moreover, 4910 and 5310 glioma xenograft
      tissue sections from mice treated with MMP-9 shRNA showed reduced expression of
      FAK/c-Myc and elevated MAD levels. Decreased co-localization of beta1 integrin
      and MMP-9 was associated with MMP-9-suppressed tumor sections. Further,
      immunoprecipitation analysis showed decreased association of proteins involved in
      telomere end repair in MMP-9 shRNA-treated glioma cells. Elevated levels of p73
      and TRAIL and the results of the FACS analysis show induction of apoptosis in MMP
      9-silenced glioma cells. Taken together, these data provide new insights into the
      mechanisms underlying MMP-9-mediated hTERT expression in glioma proliferation.

PMID- 21855632
TI  - Therapeutic neuroprotective effects of ginkgolide B on cortex and basal ganglia
      in a rat model of transient focal ischemia.
AB  - Cerebral ischemia and reperfusion is one of the leading causes for death and
      severe disabilities in the world and often lead to irreversible brain damage over
      later lifespan. The aim of this study was to investigate the evolution of
      pathological damage in cerebral cortex and basal ganglia following ischemia and
      to evaluate the therapeutic neuroprotective effect of ginkgolide B in a rat model
      of stroke induced by middle cerebral artery occlusion (MCAO). TTC stain, brain
      water content and Evans-Blue extravasation were used to quantify brain damage.
      Our results demonstrated that basal ganglia undergo progressive pathological
      damage earlier following MCAO, and injury was stable and irreversible after 5 h
      following ischemia. However, onset of ischemia injury in cerebral cortex appeared
      later than basal ganglia and became evident about 3 h following MCAO, and injury
      was stable and irreversible after 6 h following ischemia. Blood brain barrier
      opened progressively, and it seemed to be significantly destroyed after 4 h
      following MCAO comparing with 0 h. Post-ischemic treatment with ginkgolide B
      improved neurological function and reduced infarct size in basal ganglia within 3
      h and cerebral cortex within 5 h following MCAO. The therapeutic effect of
      ginkgolide B on extenuate brain edema and decrease blood brain barrier
      permeability were extended for 5h after ischemia, and more evident reversal
      effect were observed when administrated at earlier time.

PMID- 21855631
TI  - Activin, BMP and FGF pathways cooperate to promote endoderm and pancreatic
      lineage cell differentiation from human embryonic stem cells.
AB  - The study of how human embryonic stem cells (hESCs) differentiate into insulin
      producing beta cells has twofold significance: first, it provides an in vitro
      model system for the study of human pancreatic development, and second, it serves
      as a platform for the ultimate production of beta cells for transplantation into
      patients with diabetes. The delineation of growth factor interactions regulating
      pancreas specification from hESCs in vitro is critical to achieving these goals.
      In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A
      in early hESC fate determination. The entire differentiation process is carried
      out in serum-free chemically-defined media (CDM) and results in reliable and
      robust induction of pancreatic endoderm cells, marked by PDX1, and cell clusters
      co-expressing markers characteristic of beta cells, including PDX1 and insulin/C
      peptide. Varying the combinations of growth factors, we found that treatment of
      hESCs with bFGF, Activin A and BMP4 (FAB) together for 3-4days resulted in strong
      induction of primitive-streak and definitive endoderm-associated genes, including
      MIXL1, GSC, SOX17 and FOXA2. Early proliferative foregut endoderm and pancreatic
      lineage cells marked by PDX1, FOXA2 and SOX9 expression are specified in EBs made
      from FAB-treated hESCs, but not from Activin A alone treated cells. Our results
      suggest that important tissue interactions occur in EB-based suspension culture
      that contribute to the complete induction of definitive endoderm and pancreas
      progenitors. Further differentiation occurs after EBs are embedded in Matrigel
      and cultured in serum-free media containing insulin, transferrin, selenium, FGF7,
      nicotinamide, islet neogenesis associated peptide (INGAP) and exendin-4, a long
      acting GLP-1 agonist. 21-28days after embedding, PDX1 gene expression levels are
      comparable to those of human islets used for transplantation, and many PDX1(+)
      clusters are formed. Almost all cells in PDX1(+) clusters co-express FOXA2,
      HNF1beta, HNF6 and SOX9 proteins, and many cells also express CPA1, NKX6.1 and
      PTF1a. If cells are then switched to medium containing B27 and nicotinamide for 7
      14days, then the number of insulin(+) cells increases markedly. Our study
      identifies a new chemically defined culture protocol for inducing endoderm- and
      pancreas-committed cells from hESCs and reveals an interplay between FGF, Activin
      A and BMP signaling in early hESC fate determination.

PMID- 21855633
TI  - Site-directed mutagenesis of human cytosolic sulfotransferase (SULT) 2B1b to
      phospho-mimetic Ser348Asp results in an isoform with increased catalytic
      activity.
AB  - Human SULT2B1b is distinct from other SULT isoforms due to the presence of unique
      amino (N)- and carboxy (C)-terminal peptides. Using site-directed mutagenesis, it
      was determined that phosphorylation of Ser348 was associated with nuclear
      localization. To investigate the effects of this phosphorylation of Ser348 on
      activity and cellular localization, an in silico molecular mimic was generated by
      mutating Ser348 to an Asp. The Asp residue mimics the shape and charge of a
      phospho-Ser and homology models of SULT2B1b-phospho-S348 and SULT2B1b-S348D
      suggest a similar significant structural rearrangement in the C-terminal peptide.
      To evaluate the functional consequences of this post-translational modification
      and predicted rearrangement, 6His-SULT2B1b-S348D was synthesized, expressed,
      purified and characterized. The 6His-SULT2B1b-S348D has a specific activity for
      DHEA sulfation ten-fold higher than recombinant 6His-SULT2B1b (209.6 and
      21.8pmolmin(-1)mg(-1), respectively). Similar to native SULT2B1b, gel filtration
      chromatography showed SULT2B1b-S348D was enzymatically active as a homodimer.
      Stability assays comparing SULT2B1b and SUL2B1b-S348 demonstrated that SULT2B1b
      is 60% less thermostable than SULT2B1b-348D. The increased stability and
      sulfation activity allowed for better characterization of the sulfation kinetics
      for putative substrates as well as the determination of dissociation constants
      that were difficult to obtain with wild-type (WT) 6His-SULT2B1b. The K(D)s for
      DHEA and PAPS binding to 6His-SULT2B1b-S348D were 650+/-7nM and 265+/-4nM,
      respectively, whereas K(D)s for binding of substrates to the WT enzyme could not
      be determined. Characterization of the molecular mimic SULT2B1b-S348D provides a
      better understanding for the role of the unique structure of SULT2B1b and its
      effect on sulfation activity, and has allowed for improved kinetic
      characterization of the SULT2B1b enzyme.

PMID- 21855634
TI  - Monitoring virus entry into living cells using DiD-labeled dengue virus
      particles.
AB  - A variety of approaches can be applied to investigate the multiple steps and
      interactions that occur during virus entry into the host cell. Single-virus
      tracking is a powerful real-time imaging technique that offers the possibility to
      monitor virus-cell binding, internalization, intracellular trafficking behavior,
      and the moment of membrane fusion of single virus particles in living cells. Here
      we describe the development and applications of a single-virus tracking assay
      based on the use of DiD-labeled dengue virus (DENV) in BS-C-1 cells. In addition 
      and using the same experimental setup - we present a binding and fusion assay
      that can be used to obtain a rapid insight into the relative extent of virus
      binding to the cell surface and membrane fusion. Details of virus labeling and
      characterization, microscopy setup, protocols, data analysis, and hints for
      troubleshooting are described throughout the paper.

PMID- 21855635
TI  - Assessing ubiquitination of viral proteins: Lessons from flavivirus NS5.
AB  - Ubiquitin (Ub) conjugation to a substrate protein is a widely used cellular
      mechanism for control of protein stability and function, modulation of signal
      transduction pathways and antiviral responses. Identification and
      characterization of ubiquitinated viral proteins is an important step in
      understanding novel mechanisms of viral protein regulation as well as elucidating
      cellular antiviral strategies. Here we describe a protocol to easily detect and
      characterize the ubiquitination status of a viral substrate protein expressed
      either during infection or ectopically expressed as a fusion with a
      biotinylatable epitope tag. This tag provides advantages over current
      immunoprecipitation techniques by making use of the extremely tight biotin
      streptavidin interaction. We provide an example of this protocol using the
      nonstructural protein 5 (NS5) from Langat virus (LGTV), a member of the tick
      borne encephalitis virus (TBEV) serocomplex within the Flavivirus genus. Using
      the protocols outlined here, we describe some of the pitfalls inherent in
      determination of Ub linkage and demonstrate that NS5 is modified by at least two
      distinct ubiquitination types, multiubiquitination and K48-linked polyubiquitin
      chains.

PMID- 21855636
TI  - Study of early events during herpes simplex virus type 1 infection by confocal
      microscopy.
AB  - Laser scanning confocal microscopy is a powerful technique that can be applied to
      study the localisation and behaviour of proteins and nucleic acids in many
      experimental situations. It is a particularly useful technique for the study of
      virus infections because of the changes that occur in the distribution and
      amounts of both viral and cellular proteins as infection develops. These changes
      reflect key stages and important regulatory events that govern the efficiency of
      infection. Using herpes simplex virus type 1 infected cells as an experimental
      model, this article provides guidance for users new to confocal microscopy on
      basic principles and techniques. The emphasis is on recognising, diagnosing and
      avoiding potential artifacts, and the workflow of the production of high quality,
      technically correct images.

PMID- 21855637
TI  - Isotope-assisted vibrational circular dichroism investigations of amyloid beta
      peptide fragment, Abeta(16-22).
AB  - Isotope-assisted vibrational circular dichroism (VCD) investigations have been
      used to probe the site specific local structure of an amyloid peptide for the
      first time. A seven residue peptide, NH(2)-KLVFFAE-COOH, which represents the
      Abeta(16-22) fragment of the Alzheimer's amyloid beta peptide, was used for these
      investigations. (13)C labels were introduced separately at the carbonyl group of
      leucine (residue 17), alanine (residue 21) and also at both sites together. Since
      VCD spectra provide structure dependent signs, band shapes and frequencies, the
      isotope-assisted VCD spectroscopy revealed information on site specific secondary
      structure of the polypeptide. Isotope dilution VCD experiments provided a means
      to distinguish between parallel and anti-parallel nature of the beta-sheet
      structure formed by the Abeta(16-22) fragment. The current results establish the
      usefulness of isotope-assisted VCD analysis in determining the site specific
      secondary structure of amyloid peptides.

PMID- 21855638
TI  - Fetal and postnatal mouse bone tissue contains more calcium than is present in
      hydroxyapatite.
AB  - It has been shown for developing enamel and zebrafish fin that hydroxyapatite
      (HA) is preceded by an amorphous precursor, motivating us to examine the mineral
      development in mammalian bone, particularly femur and tibia of fetal and young
      mice. Mineral particle thickness and arrangement were characterized by
      (synchrotron) small-angle X-ray scattering (SAXS) combined with wide-angle X-ray
      diffraction (WAXD) and X-ray fluorescence (XRF) analysis. Simultaneous
      measurements of the local calcium content and the HA content via XRF and WAXD,
      respectively, revealed the total calcium contained in HA crystals. Interestingly,
      bones of fetal as well as newborn mice contained a certain fraction of calcium
      which is not part of the HA crystals. Mineral deposition could be first detected
      in fetal tibia at day 16.5 by environmental scanning electron microscopy (ESEM).
      SAXS revealed a complete lack of orientation in the mineral particles at this
      stage, whereas 1day after birth particles were predominantly aligned parallel to
      the longitudinal bone axis, with the highest degree of alignment in the midshaft.
      Moreover, we found that mineral particle length increased with age as well as the
      thickness, while fetal particles were thicker but much shorter. In summary, this
      study revealed strong differences in size and orientation of the mineral
      particles between fetal and postnatal bone, with bulkier, randomly oriented
      particles at the fetal stage, and highly aligned, much longer particles after
      birth. Moreover, a part of the calcium seems to be present in other form than HA
      at all stages of development.

PMID- 21855639
TI  - A novel structural mechanism for redox regulation of uridine phosphorylase 2
      activity.
AB  - Uridine phosphorylase (UPP) catalyzes the reversible conversion of uridine to
      uracil and ribose-1-phosphate and plays an important pharmacological role in
      activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5
      fluorouracil and capecitabine. Most vertebrate animals, including humans, possess
      two homologs of this enzyme (UPP1 & UPP2), of which UPP1 has been more thoroughly
      studied and is better characterized. Here, we report two crystallographic
      structures of human UPP2 (hUPP2) in distinctly active and inactive conformations.
      These structures reveal that a conditional intramolecular disulfide bridge can
      form within the protein that dislocates a critical phosphate-coordinating
      arginine residue (R100) away from the active site, disabling the enzyme. In vitro
      activity measurements on both recombinant hUPP2 and native mouse UPP2 confirm the
      redox sensitivity of this enzyme, in contrast to UPP1. Sequence analysis shows
      that this feature is conserved among UPP2 homologs and lacking in all UPP1
      proteins due to the absence of a necessary cysteine residue. The state of the
      disulfide bridge has further structural consequences for one face of the enzyme
      that suggest UPP2 may have additional functions in sensing and initiating
      cellular responses to oxidative stress. The molecular details surrounding these
      dynamic aspects of hUPP2 structure and regulation provide new insights as to how
      novel inhibitors of this protein may be developed with improved specificity and
      affinity. As uridine is emerging as a promising protective compound in neuro
      degenerative diseases, including Alzheimer's and Parkinson's, understanding the
      regulatory mechanisms underlying UPP control of uridine concentration is key to
      improving clinical outcomes in these illnesses.

PMID- 21855640
TI  - Two novel homologs of simple C-type lectin in grass carp (Ctenopharyngodon
      idellus): potential role in immune response to bacteria.
AB  - C-type lectins play important roles in glycoprotein metabolism, multicellular
      integration and immunity. Based on their overall domain structure, they can be
      classified as different groups which possess different physiological functions.
      In this study, two novel simple C-type lectins were identified from grass carp
      (Ctenopharyngodon idellus), an important cultured fish in China. GcCL1 and gcCL2
      share an essentially identical gene structure, a conserved promoter region
      shorter than 300 bp and an amino acid identity of 81.2%. Phylogenetic analysis
      indicated they may be products of gene duplication and could be classified as a
      new clade of group VII C-type lectins. Both of them were expressed in the eleven
      tissues examined, with the spleen having the highest abundance of transcript. The
      gcCL1 transcript was more abundant than gcCL2 in the majority of tissue samples
      from 2-yr-old grass carps, and was lower than those of gcCL2 before 15 days post
      hatching. The expression of both genes was significantly up-regulated in spleen,
      muscle, skin, gills and hepatopancreas after induction by Aeromonas hydrophila.
      This is the first report that the expression of group VII C-type lectins could be
      induced by a pathogen, and indicates these lectins may be involved in the immune
      response to bacteria in fish.

PMID- 21855641
TI  - The NIH experience in first advancing fMRI.
AB  - The introduction of functional MRI at NIH in 1992 was the outcome of research
      goals first formulated by Turner in 1983. Between 1988 and 1990, Turner worked at
      NIH on actively-shielded gradient coils and the implementation of EPI-based
      techniques, especially diffusion-weighted EPI. His work on hypoxia in cat brain
      in 1990 directly inspired Ken Kwong's demonstration of BOLD contrast in humans at
      MGH in May 1991. Turner collaborated actively with this MGH team, the first group
      to map entirely noninvasively human brain activity due to visual stimulation. He
      introduced BOLD fMRI at NIH in February 1992. This paper reviews the steps that
      led up to BOLD EPI, and Turner's initial applications of BOLD fMRI at NIH.

PMID- 21855642
TI  - When rediscovery is not enough: taxonomic uncertainty hinders conservation of a
      critically endangered bird.
AB  - In 2003, birds similar to the extinct New Zealand storm-petrel Oceanites
      maorianus were observed in Hauraki Gulf NZ, raising the possibility of
      rediscovery after 150 years. O. maorianus has and continues to be surrounded by
      taxonomic uncertainty, being variously described as a distinct genus, a distinct
      species, or merely a plumage variant. This uncertainty has hindered conservation
      planning and funding for the species. Here we examine the taxonomic identity of
      the rediscovered birds and museum specimens using phylogenetic analysis of
      mitochondrial (1143 bp cytochrome b) and nuclear (890 bp beta-fibrinogen) genes.
      Using cytochrome b sequence amplified from the 150+ year old specimens, we found
      that the extant and museum O. maorianus were the same taxon (0.01 genetic
      distance), with both differing from all other storm-petrel taxa. Using both
      genes, we examined the phylogenetic affinities of O. maorianus to the Oceanitinae
      and Hydrobatinae storm-petrels finding that O. maorianus was more closely aligned
      to Fregetta (0.08-0.09) than Oceanites (0.11-0.12), thereby confirming its status
      as a distinct taxon, not a plumage variant of O. oceanicus. Our analysis verifies
      that the previously presumed extinct New Zealand storm-petrel has been
      rediscovered and can now be assigned a conservation priority commensurate with
      its critically endangered status.

PMID- 21855643
TI  - An analysis of rat prefrontal cortex in mediating executive function.
AB  - While it is acknowledged that species specific differences are an implicit
      condition of comparative studies, rodent models of prefrontal function serve a
      significant role in the acquisition of converging evidence on prefrontal function
      across levels of analysis and research techniques. The purpose of the present
      review is to examine whether the prefrontal cortex (PFC) in rats supports a
      variety of processes associated with executive function including working memory,
      temporal processing, planning (prospective coding), flexibility, rule learning,
      and decision making. Therefore, in this review we examined changes associated
      with working memory processes for spatial locations, visual objects, odors,
      tastes, and response domains or attributes, temporal processes including temporal
      order, sequence learning, prospective coding, behavioral flexibility associated
      with reversal learning and set shifting, paired associate learning, and decision
      making based on effort, time discounting, and uncertainty following damage to the
      PFC in rats. In addition, potential parallel processes of executive function in
      monkeys and humans based on several theories of subregional differentiation
      within the PFC will be presented. Specifically, theories based on domain or
      attribute specificity (Goldman-Rakic, 1996), level of processing (Petrides,
      1996), rule learning based on complexity (Wise, Murray, & Gerfen, 1996),
      executive functions based on connectivity with other brain regions associated
      with top-down control (Miller & Cohen, 2001), are presented and applied to PFC
      function in rats with the aim of understanding subregional specificity in the rat
      PFC. The data suggest that there is subregional specificity within the PFC of
      rats, monkey and humans and there are parallel cognitive functions of the
      different subregions of the PFC in rats, monkeys and humans.

PMID- 21855644
TI  - Spatiotemporal dynamics of long-term potentiation in rat insular cortex revealed
      by optical imaging.
AB  - Long-term potentiation (LTP) of the gustatory cortex (GC), a part of the insular
      cortex (IC) around the middle cerebral artery, is a key process of gustatory
      learning and memory, including conditioned taste aversion learning. The rostral
      (rGC) and caudal GC (cGC) process different tastes; the rGC responds to hedonic
      and the cGC responds to aversive tastes. However, plastic changes of spatial
      interaction of excitatory propagation between the rGC and cGC remain unknown. The
      present study aimed to elucidate spatiotemporal profiles of excitatory
      propagation, induced by electrical stimulation (five train pulses) of the rGC/cGC
      before and after LTP induction, using in vivo optical imaging with a voltage
      sensitive dye. We demonstrated that tetanic stimulation of the cGC induced long
      lasting expansion of the excitation responding to five train stimulation of the
      cGC, and an increase in amplitude of optical signals in the IC. Excitatory
      propagation after LTP induction spread preferentially toward the rostral IC: the
      length constant (lambda) of excitation, obtained by fitting optical signals with
      a monoexponential curve, was increased to 121.9% in the rostral direction,
      whereas lambda for the caudal, dorsal, and ventral directions were 48.9%, 44.2%,
      and 62.5%, respectively. LTP induction was prevented by pre-application of D-APV,
      an NMDA receptor antagonist, or atropine, a muscarinic receptor antagonist, to
      the cortical surface. In contrast, rGC stimulation induced only slight LTP
      without direction preference. Considering the different roles of the rGC and cGC
      in gustatory processing, these characteristic patterns of LTP in the GC may be
      involved in a mechanism underlying conversion of palatability.

PMID- 21855645
TI  - Neuropeptide Y/peptide YY receptor Y2 duplicate in zebrafish with unique introns
      displays distinct peptide binding properties.
AB  - The neuropeptide Y-family peptides and receptors are involved in a broad range of
      functions including appetite regulation. Both the peptide genes and the receptor
      genes are known to have duplicated in early vertebrate evolution. The ancestral
      jawed vertebrate had 7 NPY receptors but the number varies between 4 and 7 in
      extant vertebrates. Herein we describe the identification of an additional NPY
      receptor in two fish species, zebrafish and medaka. They cluster together with
      the Y2 receptors in phylogenetic analyses and seem to be orthologous to each
      other that is why we have named them Y2-2. Their genes differ from Y2 in having
      introns in the coding region. Binding studies with zebrafish Y2-2 receptors show
      that the three endogenous peptides NPY, PYYa and PYYb have similar affinities,
      0.15-0.66 nM. This is in contrast to the Y2 receptor where they differed
      considerably from one another. N-terminally truncated NPY binds poorly and the Y2
      antagonist BIIE0246 binds well to Y2-2, results that are reversed in comparison
      to Y2. Zebrafish Y2-2 mRNA was detected by PCR in the intestine and the eye, but
      not in the brain. In conclusion, we have found a novel Y2-like NPY/PYY receptor
      that probably arose in early teleost fish evolution.

PMID- 21855646
TI  - Migraine: Role of the TRESK two-pore potassium channel.
AB  - Migraine is a severe episodic headache disorder affecting one in five people.
      Genetic studies have identified mutations in the CACNA1, ATP1A2 and SCN1A genes
      in the rare familial hemiplegic migraine. Recently, a mutation in the KCNK18
      gene, encoding the TRESK two-pore domain potassium channel, was described in a
      large family with migraine with aura. This review will elaborate on the possible
      role of the TRESK channel in regulating neuronal excitability, its role in
      migraine pathogenesis, and on promising therapeutic opportunities targeting this
      channel.

PMID- 21855647
TI  - Far upstream element binding protein 1 activates translation of p27Kip1 mRNA
      through its internal ribosomal entry site.
AB  - The cyclin dependent kinase inhibitor p27 plays an important role in controlling
      the eukaryotic cell cycle by regulating progression through G1 and entry into S
      phase. It is often elevated during differentiation and under conditions of
      cellular stress. In contrast, it is commonly downregulated in cancer cells and
      its levels are generally inversely correlated with favorable prognosis. The
      cellular levels of p27 are regulated, in part, by translational control
      mechanisms. The 5'-untranslated region (5'-UTR) of the p27 mRNA harbors an
      internal ribosome entry site (IRES) which may facilitate synthesis of p27 in
      certain conditions. In this study, Far Upstream Element (FUSE) Binding Protein 1
      (FBP1) was shown to directly bind to the human p27 5'-UTR and to promote IRES
      activity. An eight-nucleotide element downstream of a U-rich region within the 5'
      UTR was important for FBP1 binding and p27 IRES activity. Overexpression of FBP1
      enhanced endogenous p27 levels and stimulated translation initiation. In
      contrast, repression of FBP1 by siRNA transfection downregulated endogenous p27
      protein levels. Using rabbit reticulocyte lysates, FBP1 stimulated p27 mRNA
      translation in vitro. The central domain of FBP1, containing four K homology
      motifs, was required for p27 5'-UTR RNA binding and the N terminal domain was
      important for translational activation. These findings indicate that FBP1 is a
      novel activator of p27 translation upon binding to the 5'-UTR.

PMID- 21855648
TI  - Oxidative stress-mediated genotoxicity of wastewaters collected from two
      different stations in northern India.
AB  - Oxidative stress-mediated genotoxicity of wastewaters taken from two different
      cities, Saharanpur (SWW) and Aligarh (AWW), were compared with a battery of short
      term assays namely the Allium cepa genotoxicity test, the plasmid-nicking assay,
      and the Ames fluctuation test. Both test-water samples - when used undiluted -
      increased the frequency of chromosomal abnormalities and/or micronuclei and
      alterations in the mitotic index of root cells of Allium cepa. Bridges and
      fragmentation of the chromosome were the predominant effects of the Saharanpur
      water sample while the Aligarh sample induced mainly chromosome fragmentation.
      Single- and double-strand breaks were also observed in plasmid DNA treated with
      these test wastewaters. The plasmid-nicking assay performed on SWW resulted in
      linearization of plasmid DNA when 18MUl was tested (in a total reaction volume of
      20MUl). However, with the same amount of AWW, all three forms of plasmid, viz.
      supercoiled, open circular and linear were observed. Supplementation with
      specific scavengers of reactive oxygen species (ROS) caused a significant decline
      in mutagenicity of test-water samples in all the tests, pointing at oxidative
      stress as the mediator of the observed genotoxicity. The role of heavy metals in
      the AWW-induced oxidative stress and that of phenolics in SWW cannot be ruled
      out.

PMID- 21855649
TI  - Involvement of p53 function in different magnitude of genotoxic and cytotoxic
      responses in in vitro micronucleus assays.
AB  - In in vitro micronucleus (MN) assays the sensitivity to MN induction or
      cytotoxicity can vary depending on the kind of cells employed. This study was
      conducted to examine the involvement of the p53 function in the different
      sensitivities between Chinese hamster lung (CHL) cells and human lymphoblastoid
      TK6 cells in MN assays. MN induction and cytotoxicity were compared using MN
      inducing chemicals reported as DNA reactive clastogens, non-DNA reactive
      clastogens or aneugens. The study revealed that the maximum levels of MN
      induction in p53-compromised CHL cells were higher than those in p53-competent
      TK6 cells, but MN were significantly induced in TK6 cells at lower concentrations
      than in CHL cells. Most of the test chemicals produced a more severe cytotoxicity
      in TK6 cells, suggesting TK6 cells are more sensitive for cytotoxicity than CHL
      cells. An additional experiment with 9 MN inducers revealed that the magnitude of
      MN induction and cytotoxicity were comparable between p53-competent TK6 cells and
      its p53-null mutant NH32 cells at the same concentrations. Furthermore, the MN
      frequencies induced by methylmethane sulfonate, aphidicolin and hydroxyurea in
      NH32 cells were identical to those in TK6 cells at different recovery times. From
      these results, it is suggested that the p53 abrogation does not explain the
      difference in sensitivity to MN induction or cytotoxicity between CHL and TK6
      cells. In this regard, p53 abrogated NH32 cells can be an option for the in vitro
      MN assay.

PMID- 21855650
TI  - Banking on the future: biobanking for "omics" approaches to biomarker discovery
      for Opisthorchis-induced cholangiocarcinoma in Thailand.
AB  - Cholangiocarcinoma (CCA)--bile duct cancer--is associated with late presentation,
      poses challenges for diagnosis, and has high mortality. These features t
      highlight the desperate need for biomarkers than can be measured early and in
      accessible body fluids such as plasma of people at risk for developing this
      lethal cancer. In this manuscript, we address previous limitations in the
      discovery stage of biomarker(s) for CCA and indicate how new generation of
      "omics" technologies could be used for biomarker discovery in Thailand. A key
      factor in the success of this biomarker program for CCA is the combination of
      cutting edge technology with strategic sample acquisition by a biorepositories.

PMID- 21855652
TI  - ATP-binding cassette G5/G8 deficiency causes hypertriglyceridemia by affecting
      multiple metabolic pathways.
AB  - Mutations in ABCG5 or ABCG8 transporters are responsible for sitosterolemia, an
      autosomal recessive disease characterized by the accumulation of plant sterols.
      The aim of this study was to investigate the effects of ABCG5 and ABCG8
      deficiency on TG metabolism in mice. Experiments were carried out in wild-type
      (G5/G8+/+) mice, mice heterozygous for ABCG5 and ABCG8 deficiency (G5/G8+/-) and
      ABCG5/G8-deficient (G5/G8-/-) mice fed a chow diet. Plasma TG were 2.6 and 4.3
      fold higher in fasted G5/G8+/- and G5/G8-/- mice, respectively, than in G5/G8+/+
      mice. Postprandial TG were 5-fold higher in G5/G8-/- mice. TG metabolism studies
      indicate that: first, the fractional catabolic rate was significantly lower in
      G5/G8+/- (1.3-fold) and G5/G8-/- mice (1.5-fold) compared to G5/G8+/+ and
      postheparin plasma lipoprotein lipase activities were significantly lower in
      G5/G8+/- (1.8-fold) and G5/G8-/- mice (5.4-fold) than in G5/G8+/+. Second, liver
      TG secretion was 1.3-fold higher in G5/G8+/- and G5/G8-/- than in G5/G8+/+ mice
      and this was associated with an increase in liver LXR, FAS, ACAC and CD36 gene
      expression. Third, TG intestinal secretion, determined after an oral fat gavage
      of glycerol tri[9,10(n)-(3)H] oleate, was 5.8-fold higher in G5/G8-/- than in
      G5/G8+/+ mice. Also, the HOMA index was 2.6-fold higher in G5/G8-/- than in
      G5/G8+/+ mice, reflecting a degree of insulin resistance. In conclusion, ABCG5/G8
      deficiency in mice fed a chow diet markedly raises TG levels by impairing TG
      catabolism and by increasing liver and intestinal TG secretion.

PMID- 21855653
TI  - Naming spoligotype patterns for the RD9-deleted lineage of the Mycobacterium
      tuberculosis complex; www.Mbovis.org.
AB  - This www.Mbovis.org website and associated databases were initiated in response
      to the need of the Mycobacterium bovis molecular typing community for
      standardisation of nomenclature for spoligotype patterns. The purpose of the
      website is to provide standardised names for spoligotype patterns from strains of
      the RD9-deleted, lineage of the Mycobacterium tuberculosis complex. Each unique
      spoligotype pattern is named by 'SB' followed by a four integer number (e.g.
      SB0120) and the database currently records over 1400 patterns submitted by the
      research community over the last 9 years. The database holds information and
      authoritative names for spoligotype patterns from both clades of Mycobacterium
      africanum, M. bovis (antelope), Mycobacterium microti, Mycobacterium pinnipedii,
      Mycobacterium caprae and M. bovis. The history of the database is described, as
      well as the method for submitting new patterns to the database and the
      functionality of the website.

PMID- 21855651
TI  - Emerging roles for retinoids in regeneration and differentiation in normal and
      disease states.
AB  - The vitamin A (retinol) metabolite, all-trans retinoic acid (RA), is a signaling
      molecule that plays key roles in the development of the body plan and induces the
      differentiation of many types of cells. In this review the physiological and
      pathophysiological roles of retinoids (retinol and related metabolites) in mature
      animals are discussed. Both in the developing embryo and in the adult, RA
      signaling via combinatorial Hox gene expression is important for cell positional
      memory. The genes that require RA for the maturation/differentiation of T cells
      are only beginning to be cataloged, but it is clear that retinoids play a major
      role in expression of key genes in the immune system. An exciting, recent
      publication in regeneration research shows that ALDH1a2 (RALDH2), which is the
      rate-limiting enzyme in the production of RA from retinaldehyde, is highly
      induced shortly after amputation in the regenerating heart, adult fin, and larval
      fin in zebrafish. Thus, local generation of RA presumably plays a key role in fin
      formation during both embryogenesis and in fin regeneration. HIV transgenic mice
      and human patients with HIV-associated kidney disease exhibit a profound
      reduction in the level of RARbeta protein in the glomeruli, and HIV transgenic
      mice show reduced retinol dehydrogenase levels, concomitant with a greater than 3
      fold reduction in endogenous RA levels in the glomeruli. Levels of endogenous
      retinoids (those synthesized from retinol within cells) are altered in many
      different diseases in the lung, kidney, and central nervous system, contributing
      to pathophysiology. This article is part of a Special Issue entitled Retinoid and
      Lipid Metabolism.

PMID- 21855654
TI  - Anti-inflammatory and antinociceptive activities of indole-imidazolidine
      derivatives.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) represent a group of approximately
      50 different medicines that are widely prescribed for the management of
      inflammation and that exhibit variable anti-inflammatory, anti-pyretic and
      analgesic activities. Most NSAIDs also exhibit a shared set of adverse effects,
      particularly related to gastrointestinal complications; thus, the development of
      new drugs for the treatment of chronic inflammation and pain continues to be an
      issue of high interest. Hydantoin and indole derivatives are reported to possess
      various pharmacological effects, including anti-inflammatory and analgesic
      activities. Therefore, the aim of this study was to evaluate the potential anti
      inflammatory and antinociceptive activities of hybrid molecules containing
      imidazole and indole nuclei. The anti-inflammatory activities of 5-(1H-Indol-3-yl
      methylene)-2-thioxo-imidazolidin-4-one (LPSF/NN-56) and 3-(4-Bromo-benzyl)-5-(1H
      indol-3-yl-methylene)-2thioxo-imidazolidin-4-one (LPSF/NN-52) were evaluated
      using air pouch and carrageenan-induced peritonitis models as well as an acetic
      acid-induced vascular permeability model followed by IL-1beta and TNF-alpha
      quantification. To evaluate the antinociceptive activities of the compounds,
      acetic acid-induced nociception, formalin and hot plate tests were also
      performed. The anti-inflammatory activities of the compounds were evidenced by a
      reduction in both leukocyte migration and the release of TNF-alpha and IL-1beta
      in air pouch and peritonitis models. Upon acetic acid-induced nociception, a
      decrease in the level of abdominal writhing in the groups treated with LPSF/NN-52
      (52.1%) or LPSF/NN-56 (63.1%) was observed. However, in the hot plate test, none
      of the derivatives tested exhibited an inhibition of nociception. These results
      indicate that the compounds tested exhibited promising anti-inflammatory and
      antinociceptive activities that likely involved the modulation of the immune
      system.

PMID- 21855655
TI  - Optimization of respiratory chain enzymatic assays in muscle for the diagnosis of
      mitochondrial disorders.
AB  - The diagnosis of mitochondrial disorders is difficult due to clinical and genetic
      heterogeneity. Measurements of mitochondrial respiratory chain (RC) enzyme
      activities are essential for both clinical diagnoses and many basic research
      questions. Current protocols for RC analysis are not standardized, and so are
      prone to inter-laboratory variability, and also to biochemical interferences that
      lead to analytical discrepancies. Moreover, knowledge of the analytical
      performances of these assays, which is essential to draw meaningful conclusions
      from the results, is lacking. To understand this variability and to propose
      possible solutions, we systematically investigated the effect of different
      homogenization protocols and chemical conditions on RC assays using muscle
      homogenates. We developed optimized protocols and a novel complex III method with
      improved sensitivity, precision, and linearity. These methods can be reliably
      performed on minute muscle samples with a single-wavelength spectrophotometer.
      Moreover, we measured the variability of the proposed homogenization protocol and
      we provide a systematic evaluation of each assay's specificity, precision, and
      linearity. These data will be useful for quality control in both clinical and
      research laboratories.

PMID- 21855656
TI  - Pathogenesis of Takayasu's arteritis: a 2011 update.
AB  - While our knowledge of the pathogenesis of Takayasu's arteritis (TA) has
      considerably improved during the last decade, the exact pathogenic sequence
      remains to be elucidated. It is now hypothesised that an unknown stimulus
      triggers the expression of the 65kDa Heat-shock protein in the aortic tissue
      which, in turn, induces the Major Histocompatibility Class I Chain-Related A
      (MICA) on vascular cells. The gammadelta T cells and NK cells expressing NKG2D
      receptors recognize MICA on vascular smooth muscle cells and release perforin,
      resulting in acute vascular inflammation. Pro-inflammatory cytokines are released
      and increase the recruitment of mononuclear cells within the vascular wall. T
      cells infiltrate and recognize one or a few antigens presented by a shared
      epitope, which is associated with specific major Histocompatibility Complex
      alleles on the dendritic cells, these latter being activated through Toll-like
      receptors. Th1 lymphocytes drive the formation of giant cells through the
      production of interferon-gamma, and activate macrophages with release of VEGF
      resulting in increased neovascularisation and PDGF, resulting in smooth muscle
      migration and intimal proliferation. Th17 cells induced by the IL-23
      microenvironnement also contribute to vascular lesions through activation of
      infiltrating neutrophils. Although still controversial, dendritic cells may
      cooperate with B lymphocytes and trigger the production of anti-endothelial cell
      auto-antibodies resulting in complement-dependent cytotoxicity against
      endothelial cells. In a near future, novel drugs specifically designed to target
      some of the pathogenic mechanisms described above could be expanding the
      physician's therapeutic arsenal in Takayasu's arteritis.

PMID- 21855657
TI  - Neurological outcome after experimental lung injury.
AB  - We examined the influences of acute lung injury and hypoxia on neurological
      outcome. Functional performance was assessed using a neurocognitive test and a
      neurologic deficit score (NDS) five days before. On experimental day,
      mechanically ventilated pigs were randomized to hypoxia only (HO group, n=5) or
      to acute lung injury (ALI group, n=5). Hemodynamics, respiratory mechanics,
      systemic cytokines and further physiologic variables were obtained at baseline,
      at the time of ALI, 2, 4 and 8h thereafter. Subsequently, injured lungs were
      recruited and animals weaned from the ventilator. Neurocognitive testing was re
      examined for five days. Then, brains were harvested for neurohistopathology.
      After the experiment, neurocognitive performance was significantly worsened and
      the NDS increased in the ALI group. Histopathology revealed no significant
      differences. Oxygenation was comparable between groups although significantly
      higher inspiratory pressures occured after ALI. Cytokines showed a trend towards
      higher levels after ALI. Neurocognitive compromise after ALI seems due to a more
      pronounced inflammatory response and complex mechanical ventilation.

PMID- 21855658
TI  - Effect of training on airways inflammatory response and remodeling in a rat
      model.
AB  - Training has many beneficial effects, however few studies report its effects on
      the lungs. The aim of this study was to assess the effects of acute exercise and
      exercise training on inflammatory responses and remodeling in central and
      peripheral airways. Sixteen Sprague-Dawley rats trained for 10 weeks, while 14
      rats served as controls. Before sacrifice, 8 trained (TR(AC)) and 8 untrained
      control (CON(AC)) rats underwent a single acute exercise bout, while 8 trained
      (TR) and 6 untrained control (CON) rats were sacrificed without acute exercise.
      The central and peripheral airways were morphologically examined for inflammatory
      cells and immunostained for decorin, collagen I, alpha-smooth muscle actin. No
      significant differences were found for morphometric analysis in central and
      peripheral airways, however CON(AC) showed a significant increase in
      polymorphonuclear cells in the central airways compared to CON. In contrast,
      TR(AC) did not show an inflammatory response different from TR. A similar trend
      was present in peripheral airways. Training did not induce differences in airways
      inflammation and remodeling as compared to CON. However, training seemed to limit
      the inflammatory response induced by acute exercise in the central airways.

PMID- 21855659
TI  - Criteria impacting the cellular uptake of nanoparticles: a study emphasizing
      polymer type and surfactant effects.
AB  - A detailed understanding of the particle-cell interaction is essential and of
      immense interest in order to create a "specific carrier" for each particular
      application. In this paper, the effect of the surfactant type (non-ionic vs
      ionic) and polymer nature on the cellular uptake of fluorescent polystyrene and
      poly(L-lactide) nanoparticles was studied on HeLa cells. Nanoparticles in a size
      range from 100 to 160 nm were synthesized by the miniemulsion process. The
      particles were detected in cells by confocal laser scanning fluorescence
      microscopy and flow cytometry. It was found that the influence of the surface
      charge is greater than that of the polymer type itself. In fact, particles
      stabilized with cationic surfactant were incorporated in a large number
      irrespective of polymer type. Cellular pathways at ultrastructural level were
      studied by transmission electron microscopy in more detail to shed light on the
      particle-cell interaction based on the material properties. The criteria
      governing the cellular uptake of nanoparticles based on the polymer and
      surfactant types are finally established.

PMID- 21855660
TI  - Orientation of human osteoblasts on hydroxyapatite-based microchannels.
AB  - The effect of calcium phosphate-based microchannels on the growth and orientation
      of human osteoblast cells is investigated in this study. As substrates,
      hydroxyapatite-based microchannels with high contouring accuracy were fabricated
      by a novel micro-moulding technique. Microchannels obtained by this method
      featured widths ranging from 16.0+/-0.7 to 76.6+/-1.4 MUm and depths from 7.9+/
      0.8 to 15.5+/-1.3 MUm. Surface and contour characterization was carried out using
      X-ray diffraction analysis, scanning electron microscopy imaging and 3D-confocal
      profilometry. Cell activity and alignment on microchannels with different widths
      were determined after 1 and 3 days by photometric spectroscopy and fluorescence
      microscopic imaging and statistically analysed by Tukey's multiple comparison
      test. On days 1 and 3 for microchannels of width 16 and 30 MUm, 70-80% of the
      osteoblasts oriented within an angular range of 0-15 degrees  relative to the
      microchannel direction. Interestingly, only 20% of the cells grew inside the
      microchannels for channel widths of 16 and 30 MUm. Substrates with channel widths
      of 45, 65 and 76 MUm allowed ~40% of the cells to grow inside. The depth of the
      microchannel showed hardly any significant impact. All micropatterned surfaces
      provoked a good cell attachment, as flat and spread cell morphologies with
      lamellipodiae and filopodiae could already be observed after 1 day. The effect of
      the microchannels on osteoblast activity was determined using the colorimetric
      WST-1 assay. In addition, the cell differentiation was assessed by collagen type
      I staining. The cell activity obtained by WST-1 assay differed insignificantly
      for all micropatterned samples of various widths and depths. The assessment of
      collagen type I yielded the same amounts for all micropatterned samples after 1,
      3 and 7 days. In summary, the microchannel width of HA-based patterns has a
      distinct effect on the directed growth of human osteoblast cells, allowing novel
      design strategies for surfaces such as dental implants.

PMID- 21855661
TI  - Porous and strong bioactive glass (13-93) scaffolds prepared by unidirectional
      freezing of camphene-based suspensions.
AB  - Scaffolds of 13-93 bioactive glass (6Na(2)O, 12K(2)O, 5MgO, 20CaO, 4P(2)O(5),
      53SiO(2); wt.%) with an oriented pore architecture were formed by unidirectional
      freezing of camphene-based suspensions, followed by thermal annealing of the
      frozen constructs to grow the camphene crystals. After sublimation of the
      camphene, the constructs were sintered (1 h at 700 degrees C) to produce a dense
      glass phase with oriented macropores. The objective of this work was to study how
      constant freezing rates (1-7 degrees C min(-1)) during the freezing step
      influenced the pore orientation and mechanical response of the scaffolds. When
      compared to scaffolds prepared by freezing the suspensions on a substrate kept at
      a constant temperature of 3 degrees C (time-dependent freezing rate), higher
      freezing rates resulted in better pore orientation, a more homogeneous
      microstructure and a marked improvement in the mechanical response of the
      scaffolds in compression. Scaffolds fabricated using a constant freezing rate of
      7 degrees C min(-1) (porosity=50+/-4%; average pore diameter=100 MUm), had a
      compressive strength of 47+/-5 MPa and an elastic modulus of 11+/-3 GPa (in the
      orientation direction). In comparison, scaffolds prepared by freezing on the
      constant-temperature substrate had strength and modulus values of 35+/-11 MPa and
      8+/-3 GPa, respectively. These oriented bioactive glass scaffolds prepared by the
      constant freezing rate route could potentially be used for the repair of defects
      in load-bearing bones, such as segmental defects in the long bones.

PMID- 21855662
TI  - Nanostructuring biosynthetic hydrogels for tissue engineering: a cellular and
      structural analysis.
AB  - The nanostructuring of hydrogel scaffolds used in tissue engineering provides the
      ability to control cellular fate and tissue morphogenesis through cell-matrix
      interactions. Here we describe a method to provide nanostructure to a
      biosynthetic hydrogel scaffold made from crosslinked poly(ethylene glycol)
      fibrinogen conjugates (PEG-fibrinogen), by modifying them with the block
      copolymer Pluronic(r) F127. The copolymeric additive self-assembled into micelles
      at certain concentrations and temperatures, thereby creating nanostructures
      within the crosslinked hydrogel. Small-angle X-ray scattering (SAXS) and
      transmission electron microscopy at cryogenic temperature were used to detect
      Pluronic(r) F127 micelles embedded within the crosslinked PEG-fibrinogen
      hydrogels. The density and order of the micelles within the hydrogel matrix
      increased as the relative Pluronic(r) F127 concentration was raised. The
      transient stability of the micelles within the hydrogel network was analyzed
      using time-dependent swelling and Pluronic(r) F127 release measurements. These
      characterizations revealed that most of the Pluronic(r) F127 molecules diffuse
      out of the hydrogels after 4 days in aqueous buffer and SAXS analysis confirmed a
      significant change in the structure and interactions of the micelles during this
      time. Cell culture experiments evaluating the three-dimensional fibroblast
      morphology within the matrix indicated a strong correlation between cell
      spreading and the hydrogel's characteristic mesh size. The present research
      thereby provides a more quantitative understanding of how structural features in
      an encapsulating hydrogel environment can affect cell morphogenesis towards
      tissue regeneration.

PMID- 21855663
TI  - The effect of processing variables on morphological and mechanical properties of
      supercritical CO2 foamed scaffolds for tissue engineering.
AB  - The porous structure of a scaffold determines the ability of bone to regenerate
      within this environment. In situations where the scaffold is required to provide
      mechanical function, balance must be achieved between optimizing porosity and
      maximizing mechanical strength. Supercritical CO(2) foaming can produce open
      cell, interconnected structures in a low-temperature, solvent-free process. In
      this work, we report on foams of varying structural and mechanical properties
      fabricated from different molecular weights of poly(DL-lactic acid) P(DL)LA (57,
      25 and 15 kDa) and by varying the depressurization rate. Rapid depressurization
      rates produced scaffolds with homogeneous pore distributions and some closed
      pores. Decreasing the depressurization rate produced scaffolds with wider pore
      size distributions and larger, more interconnected pores. In compressive testing,
      scaffolds produced from 57 kDa P(DL)LA exhibited typical stress-strain curves for
      elastomeric open-cell foams whereas scaffolds fabricated from 25 and 15 kDa
      P(DL)LA behaved as brittle foams. The structural and mechanical properties of
      scaffolds produced from 57 kDa P(DL)LA by scCO(2) ensure that these scaffolds are
      suitable for potential applications in bone tissue engineering.

PMID- 21855664
TI  - Viscoelastic effects during loading play an integral role in soft tissue
      mechanics.
AB  - Viscoelastic relaxation during tensioning is an intrinsic protective mechanism of
      biological soft tissues. However, current viscoelastic characterization
      methodologies for these tissues either negate this important behavior or provide
      correction methods that are severely restricted to a specific viscoelastic
      formulation and/or assume an a priori (linear) strain ramp history. In order to
      address these shortcomings, we present a novel finite ramp time correction method
      for stress relaxation experiments (to incorporate relaxation manifested during
      loading) that is independent of a specific viscoelastic formulation and can
      accommodate an arbitrary strain ramp history. We demonstrate transferability of
      our correction method between viscoelastic formulations by applying it to quasi
      linear viscoelastic (QLV) and fully nonlinear viscoelastic constitutive
      equations. The errors associated with currently accepted methodologies for QLV
      and fully nonlinear viscoelastic formulations are elucidated. Our correction
      method is validated by demonstrating the ability of its fitted parameters to
      predict an independent cyclic experiment across multiple strain amplitudes and
      frequencies. The results presented herein: (i) indicate that our correction
      method significantly reduces the errors associated with previous methodologies;
      and (ii) demonstrate the necessity for the use of a fully nonlinear viscoelastic
      formulation, which incorporates relaxation manifested during loading, to model
      the viscoelastic behavior of biological soft tissues.

PMID- 21855665
TI  - Functional analysis of beef tenderness.
AB  - Meat tenderness represents a complex assembly of different cellular pathways. As
      a consequence, genomics studies have revealed many different proteins considered
      as tenderness markers. So it is difficult to have an overview of tenderness in
      terms of cellular pathways. In this work cellular pathways of tenderness were
      analyzed, an interactome of 330 proteins was designed, and explanations of
      tenderization processes were proposed.

PMID- 21855666
TI  - Viral miRNAs exploiting the endosomal-exosomal pathway for intercellular cross
      talk and immune evasion.
AB  - The class of persistent gamma-herpesviruses has developed a variety of strategies
      that exploit host-cell regulatory pathways to ensure a long-lasting, well
      balanced infection of their host. However when these pathways are deregulated, an
      otherwise harmless infection can lead to disease including cancer. We recently
      demonstrated that the human herpes virus 4 (HHV4) also known as Epstein-Barr
      virus (EBV), encodes for small regulatory non-coding microRNAs (miRNAs) that can
      be transferred from an infected cell to uninfected neighboring cells. Upon
      arrival these miRNAs are functional in the recipient cell, in that they are able
      to down regulate specific target genes. These secreted miRNAs are transported to
      recipient cells via small nano-sized vesicles (known as exosomes) that are of
      endosomal origin, formed as intraluminal vesicles (ILV) inside multivesicular
      bodies (MVB). One question that needs to be addressed is how viral miRNAs are
      sorted into these exosomes. Mature miRNAs, including those of viral origin, are
      loaded into RNA-induced silencing complexes (RISC) for gene silencing via
      blocking mRNA translation and/or initiating mRNA decay. Recent insights indicate
      that cytoplasmic RNA granules rich in RISC complexes are closely associated with
      endosomes. In fact, selective components of RISC, including GW182 and Argonaut
      proteins, miRNAs and mRNAs are present in exosomes. Thus miRNA function, mRNA
      stability and exosome-mediated intercellular communication converge at the level
      of endosomes. Since endosomes can be considered as key intracellular cross-roads
      that regulate communication of cells with their exterior, including neighboring
      cells, it is perhaps not surprising that viruses have found means to exploit this
      pathway to their benefit. Little is known however, how and if (micro) RNA species
      are specifically sorted into ILVs and what (micro)RNA-binding proteins are
      involved. Here we discuss recent developments relating to intracellular
      trafficking and function of miRNA-containing protein complexes that EBV may
      exploit for promoting or restricting miRNAs sorting into exosomes for
      intercellular regulatory functions. This article is part of a Special Issue
      entitled: MicroRNAs in viral gene regulation.

PMID- 21855668
TI  - High-bone-mass-producing mutations in the Wnt signaling pathway result in
      distinct skeletal phenotypes.
AB  - Mutations among genes that participate in the canonical Wnt signaling pathway can
      lead to drastically different skeletal phenotypes, ranging from severe
      osteoporosis to severe osteosclerosis. Many high-bone-mass (HBM) causing
      mutations that occur in the LRP5 gene appear to impart the HBM phenotype, in
      part, by increasing resistance to soluble Wnt signaling inhibitors, including
      sclerostin. Sost loss-of-function mutant mice (Sost knock-out) and Lrp5 gain-of
      function mutant mice (Lrp5 HBM knock-in) have high bone mass. These mutants
      potentially would be predicted to be phenocopies of one another, because in both
      cases, the sclerostin-Lrp5 interaction is disrupted. We measured bone mass, size,
      geometry, architecture, and strength in bones from three different genetic mouse
      models (Sost knock-out, Lrp5 A214V knock-in, and Lrp5 G171V knock-in) of HBM. We
      found that all three mouse lines had significantly elevated bone mass in the
      appendicular skeleton and in the cranium. Sost mutants and Lrp5 A214V mutants
      were statistically indistinguishable from one another in most endpoints, whereas
      both were largely different from the Lrp5 G171V mutants. Lrp5 G171V mutants
      preferentially added bone endocortically, whereas Lrp5 A214V and Sost mutants
      preferentially added bone periosteally. Cranial thickness and cranial nerve
      openings were similarly altered in all three HBM models. We also assessed serum
      serotonin levels as a possible mechanism accounting for the observed changes in
      bone mass, but no differences in serum serotonin were found in any of the three
      HBM mouse lines. The skeletal dissimilarities of the Lrp5 G171V mutant to the
      other mutants suggest that other, non-sclerostin-associated mechanisms might
      account for the changes in bone mass resulting from this mutation.

PMID- 21855669
TI  - Change in porosity is the major determinant of the variation of cortical bone
      elasticity at the millimeter scale in aged women.
AB  - At the mesoscale (i.e. over a few millimeters), cortical bone can be described as
      two-phase composite material consisting of pores and a dense mineralized matrix.
      The cortical porosity is known to influence the mesoscopic elasticity. Our
      objective was to determine whether the variations of porosity are sufficient to
      predict the variations of bone mesoscopic anisotropic elasticity or if change in
      bone matrix elasticity is an important factor to consider. We measured 21
      cortical bone specimens prepared from the mid-diaphysis of 10 women donors (aged
      from 66 to 98 years). A 50-MHz scanning acoustic microscope (SAM) was used to
      evaluate the bone matrix elasticity (reflected in impedance values) and porosity.
      Porosity evaluation with SAM was validated against Synchrotron Radiation MUCT
      measurements. A standard contact ultrasonic method was applied to determine the
      mesoscopic elastic coefficients. Only matrix impedance in the direction of the
      bone axis correlated to mesoscale elasticity (adjusted R(2)=[0.16-0.25], p<0.05).
      The mesoscopic elasticity was found to be highly correlated to the cortical
      porosity (adj-R(2)=[0.72-0.84], p<10(-5)). Multivariate analysis including both
      matrix impedance and porosity did not provide a better statistical model of
      mesoscopic elasticity variations. Our results indicate that, for the elderly
      population, the elastic properties of the mineralized matrix do not undergo large
      variations among different samples, as reflected in the low coefficients of
      variation of matrix impedance (less than 6%). This work suggests that change in
      the intracortical porosity accounts for most of the variations of mesoscopic
      elasticity, at least when the analyzed porosity range is large (3-27% in this
      study). The trend in the variation of mesoscale elasticity with porosity is
      consistent with the predictions of a micromechanical model consisting of an
      anisotropic matrix pervaded by cylindrical pores.

PMID- 21855670
TI  - Emerging evidence concerning systemic safety of anti-VEGF agents--should
      ophthalmologists be concerned?

PMID- 21855671
TI  - Intraocular pressure: modulation as treatment for glaucoma.
AB  - PURPOSE: To review the role of intervisit intraocular pressure (IOP) fluctuation
      as an independent risk factor for glaucoma. DESIGN: Perspective after literature
      review. METHODS: Analysis of pertinent publications in the peer-reviewed
      literature. RESULTS: Disparate findings regarding the role of intervisit IOP
      variation have been published. IOP variation was a significant risk factor in the
      Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma
      Treatment Study, and other smaller studies. These studies have in common low IOPs
      (often after surgery) and moderately advanced disease. In the AGIS, when patients
      were stratified by mean IOP, only those patients with low IOPs showed the
      detrimental effects of IOP variation. IOP variation was not a significant risk
      factor in the Early Manifest Glaucoma Treatment Trial, and in 2 separate studies
      of ocular hypertensives. These studies have in common generally higher IOPs and
      an earlier stage of glaucoma (or no glaucoma at all). We believe these results
      are complementary rather than contradictory: existing data suggest that the
      effects of IOP variation depend on the characteristics of the patient, the
      baseline IOP, their stage of damage, the type of glaucoma, and other as-yet
      unknown factors. CONCLUSIONS: Practitioners should consider whether patients who
      are progressing at low mean IOP may benefit from having IOP variation reduced.
      Single elevated measures of IOP may not be an anomaly or may not be related to
      compliance, but may identify patients who are at high risk for progressive
      glaucomatous damage, and thus should be monitored more carefully and potentially
      treated more aggressively.

PMID- 21855673
TI  - Polymorphisms in ARMS2 (LOC387715) and LOXL1 genes in the Japanese with age
      related macular degeneration.

PMID- 21855674
TI  - Pulsar perimetry in the diagnosis of early glaucoma.

PMID- 21855676
TI  - Success rates of trabeculotomy for steroid-induced glaucoma: a comparative,
      multicenter, retrospective cohort study.

PMID- 21855678
TI  - Success rates of trabeculotomy for steroid-induced glaucoma: a comparative,
      multicenter, retrospective cohort study.

PMID- 21855679
TI  - Retinal nerve fiber layer thickness in children with optic pathway gliomas.

PMID- 21855682
TI  - Intact pericellular matrix of articular cartilage is required for unactivated
      discoidin domain receptor 2 in the mouse model.
AB  - Increased expression of the discoidin domain receptor 2 (DDR2) results from its
      interaction with collagen type II. This induces expression of matrix
      metalloproteinase (MMP)-13, leading to osteoarthritis (OA). To investigate the
      impact of the pericellular matrix of chondrocytes on DDR2, we generated a mouse
      model with inducible overexpression of DDR2 in cartilage. Conditional
      overexpression of DDR2 in mature mouse articular cartilage was controlled via the
      cartilage oligomeric matrix protein promoter using the Tet-Off-inducible system.
      Doxycycline was withdrawn at 1 month of age, and knee joints were examined at 2,
      3, and 4 months of age. Microsurgery was performed on 3-month-old transgenic mice
      overexpressing DDR2 to destabilize the medial meniscus, and serial paraffin
      sections were examined at 2, 4, 8, and 12 weeks after surgery. DDR2 expression
      increased in the knee joints of transgenic mice. However, the increased DDR2 did
      not induce MMP-13 expression. No OA-like changes were observed in the transgenic
      mice at the age of 4 months. When transgenic mice were subjected to destabilizing
      of the medial meniscus, we observed accelerated progression to OA, which was
      associated with DDR2 activation. Therefore, conditionally overexpressing DDR2 in
      the mature articular cartilage of mouse knee joints requires activation to induce
      OA, and altered biomechanical stress can accelerate the onset of cartilage loss
      and progression to OA in transgenic mice.

PMID- 21855683
TI  - Inclusion body myositis: laser microdissection reveals differential up-regulation
      of IFN-gamma signaling cascade in attacked versus nonattacked myofibers.
AB  - Sporadic inclusion body myositis (IBM) is a muscle disease with two separate
      pathogenic components, degeneration and inflammation. Typically, nonnecrotic
      myofibers are focally surrounded and invaded by CD8(+) T cells and macrophages.
      Both attacked and nonattacked myofibers express high levels of human leukocyte
      antigen class I (HLA-I) molecules, a prerequisite for antigen presentation to
      CD8(+) T cells. However, only a subgroup of HLA-I(+) myofibers is attacked by
      immune cells. By using IHC, we classified myofibers from five patients with
      sporadic IBM as attacked (A(IBM)) or nonattacked (N(IBM)) and isolated the
      intracellular contents of myofibers separately by laser microdissection. For
      comparison, we isolated myofibers from control persons (H(CTRL)). The samples
      were analyzed by microarray hybridization and quantitative PCR. HLA-I up
      regulation was observed in A(IBM) and N(IBM), whereas H(CTRL) were negative for
      HLA-I. In contrast, the inducible chain of the interferon (IFN) gamma receptor
      (IFNGR2) and several IFN-gamma-induced genes were up-regulated in A(IBM) compared
      with N(IBM) and H(CTRL) fibers. Confocal microscopy confirmed segmental IFNGR2 up
      regulation on the membranes of A(IBM), which positively correlated with the
      number of adjacent CD8(+) T cells. Thus, the differential up-regulation of the
      IFN-gamma signaling cascade observed in the attacked fibers is related to local
      inflammation, whereas the ubiquitous HLA-I expression on IBM muscle fibers does
      not require IFNGR expression.

PMID- 21855685
TI  - Development of an indirect-cost calculation model suitable for workplace use.
AB  - INTRODUCTION: Occupational Health and Safety (OHS) stakeholders rarely factor the
      cost of workplace accidents into prevention spending decisions. The lack of
      consideration of this key information is related to the fact that the scientific
      literature has failed to provide OHS stakeholders with a cost-calculation tool
      that is both sufficiently accurate and does not require a data-collection stage
      ill-suited to the time constraints of workplace decision-makers. METHOD: This
      study reviews the recent literature to identify key elements that should foster
      the use of indirect-cost calculation methods by decision makers. RESULTS: A
      "local" approach currently appears to be the best method for calculating indirect
      costs of workplace incidents or accidents in comparison to "bottom-up" or "top
      down" approach. This paper discusses four criteria that this type of approach
      must satisfy to be compatible with the time constraints and accuracy demands of
      OHS stakeholders in organizations. In addition, four bases for the development of
      a new indirect cost estimation model are presented and discussed. IMPACT ON
      INDUSTRY: this study provides bases and criteria to help the development of
      indirect-cost calculation models better suited to workplace use than those
      currently available.

PMID- 21855686
TI  - Road safe seniors: Screening for age-related driving disorders in inpatient and
      outpatient settings.
AB  - INTRODUCTION: Older drivers are increasing in number and they often have health
      conditions that place them at high risk for motor-vehicle crashes (MVC).
      Screening is underutilized, and is rarely done in hospital settings. METHODS: A
      convenience sample of 755 older adults completed age related driving disorders
      screening at University of California, San Diego inpatient and outpatient health
      centers. Screening included three strength/frailty tests, two vision tests
      (acuity and fields), and two cognitive tests, based on AMA recommendations. The
      average age of participants was 72.5; 55.5% were male and 94% English-speaking;
      17.8% of older adults failed at least one aspect of screening. RESULTS: In
      multivariate analysis, significant associations of failed status were age, male
      sex, selfrestrictions of driving, and inpatient screening locations. The
      screening identified one in six adults to be 'high-risk' for age related driving
      disorders. Screening was effective and feasible in both inpatient and outpatient
      settings. IMPACT ON INDUSTRY: As the driving population ages, industry,
      government and health car providers need to plan for the management of driving
      impairments in older adults.

PMID- 21855684
TI  - The tryptophan metabolite 3-hydroxyanthranilic acid plays anti-inflammatory and
      neuroprotective roles during inflammation: role of hemeoxygenase-1.
AB  - Tryptophan metabolism by the kynurenine pathway (KP) is important to the
      pathogenesis of inflammatory, infectious, and degenerative diseases. The 3
      hydroxykynurenine (3-HK) branch of the KP is activated in macrophages and
      microglia, leading to the generation of 3-HK, 3-hydroxyanthranilic acid (3-HAA),
      and quinolinic acid, which are considered neurotoxic owing to their free radical
      generating and N-methyl-d-aspartic acid receptor agonist activities. We
      investigated the role of 3-HAA in inflammatory and antioxidant gene expression
      and neurotoxicity in primary human fetal central nervous system cultures treated
      with cytokines (IL-1 with or without interferon-gamma) or with Toll-like receptor
      ligands mimicking the proinflammatory central nervous system environment. Results
      were analyzed by microarray, Western blot, immunostain, enzyme-linked
      immunosorbent assay, and neurotoxicity assays. 3-HAA suppressed glial cytokine
      and chemokine expression and reduced cytokine-induced neuronal death. 3-HK also
      suppressed cytokine-induced neuronal death. Unexpectedly, 3-HAA was highly
      effective in inducing in astrocytes the expression of hemeoxygenase-1 (HO-1), an
      antioxidant enzyme with anti-inflammatory and cytoprotective properties. Optimal
      induction of HO-1 required 3-HAA and cytokines. In human microglia, 3-HAA weakly
      induced HO-1 and lipopolysaccharide suppressed microglial HO-1 expression. 3-HAA
      mediated HO-1 expression was confirmed in cultured adult human astrocytes and in
      vivo after 3-HAA injection to mouse brains. Together, our results demonstrate the
      novel neuroprotective activity of the tryptophan metabolite 3-HAA and have
      implications for future therapeutic approaches for neuroinflammatory disorders.

PMID- 21855687
TI  - Deprived neighborhoods and risk of road trauma (incidence and severity) among
      under 25year-olds in the Rhone Departement (France).
AB  - INTRODUCTION: Previous research has shown that there are inequalities with regard
      to traffic accident risk between different social categories. This study
      describes the influence of the type of residential municipality (with or without
      deprived urban areas, "ZUS, zones urbaines sensibles"), used as an indicator of
      contextual deprivation, on the incidence and severity of road trauma involving
      people of under 25years of age in the Rhone. METHOD: Injury data were taken from
      The Rhone Road Trauma Registry. The study covers the 2004-2007 period, with
      13,589 young casualties. The incidence of traffic injury of all severities were
      computed according to the type of municipality and the age, gender, and type of
      road user. The ratios of the incidences of deprived municipalities, compared with
      others were calculated. Subsequently the severity factors and incidences
      according to the severity level (ISS 1-8, ISS 9+) were studied. RESULTS: For the
      main types of road users except motorized two-wheeler users, the incidences were
      higher in the deprived municipalities: the greatest difference was for
      pedestrians, where the incidences were almost twice those of other
      municipalities. This excess risk, constituting a health inequality topic rarely
      considered, was even greater in municipalities with two or three ZUSs. It was
      essentially observed for minor injuries among motorists, cyclists, and
      pedestrians. CONCLUSIONS: While the incidence increased among people less than
      25years of age, the severity of road injuries was lower in deprived
      neighborhoods, contrary to what is suggested by other studies. This lower
      severity disappeared when taking into account the crash characteristics. IMPACT
      ON INDUSTRY: The incidence of injuries as a pedestrian, cyclist or motorist is
      higher among young people living in deprived municipalities. These areas should
      therefore be the targets of dedicated education programs, as well as further
      investigations about urban planning.

PMID- 21855688
TI  - Overview of motorcycling in the United States: a national telephone survey.
AB  - OBJECTIVES: Motorcycle registrations have risen in recent years. Although
      motorcyclist crash fatalities in 2009 were 16% lower than in 2008, they were
      double the number of deaths in 1997. The present study examined current
      motorcyclists' travel patterns and views of motorcycle helmets and other safety
      topics. METHODS: Motorcycle drivers were interviewed in a national telephone
      survey conducted in 2009. A weighted sample of 1,606 motorcyclists resulted from
      adjusting for the oversampling of those younger than 40 and those in the three
      states without a motorcycle helmet use law (Illinois, Iowa, New Hampshire). All
      analyses were based on the weighted sample, which was intended to result in a
      nationally representative sample of motorcyclists. RESULTS: About one-quarter of
      respondents said they did not always wear helmets. Of these respondents, 57% said
      a law requiring helmet use would persuade them to do so, and 27% said nothing
      would. Ninety-four percent of respondents in states with universal helmet laws
      said they always ride helmeted, compared with about half of respondents in other
      states. About half of all respondents favored these laws. About three-quarters
      said they believe helmets keep riders safer, including two-thirds of respondents
      who oppose universal laws and almost half of drivers who rarely/never wear
      helmets. Drivers ages 18-29 and drivers of sport/unclad sport, sport touring, and
      super sport motorcycles were more likely to always wear helmets, support
      universal helmet laws, and believe helmets keep riders safer. About half of
      respondents said antilock braking systems (ABS) enhance safety and that they
      would get ABS on their next motorcycle. Less than one-quarter thought an airbag
      would protect a motorcyclist in a crash, and even fewer would consider getting
      one on their next motorcycle. Forty-three percent of motorcyclists said they had
      crashed at least once; 62% of the most recent crashes involved no vehicles
      besides the motorcycle. Respondents reported riding their motorcycles about 5,400
      miles, on average, during the past year. Drivers ages 18-29 reported riding fewer
      miles, on average, than older drivers and more often rode at night and to/from
      work or school. Drivers of touring and sport touring motorcycles traveled more
      miles and took more long trips. CONCLUSIONS: Motorcyclists' travel patterns and
      views vary widely, but there are distinct patterns by driver age and motorcycle
      type. Drivers who believe helmets keep riders safer are more likely to always
      wear them, but this belief appears insufficient to motivate some drivers to wear
      them. However, universal helmet laws appear effective in increasing helmet use.
      Many drivers are receptive to purchasing ABS on their next motorcycle. IMPACT ON
      INDUSTRY: States should be encouraged to enact universal helmet laws, and
      motorcycle manufacturers should be encouraged to offer ABS.

PMID- 21855690
TI  - Driving exposure by driver age in Michigan.
AB  - BACKGROUND: This study compared driving exposure between two high-crash-risk
      groups (16-17 and 18-24-year-olds), with a low-crash-risk group (35-64-year
      olds). In addition, patterns of association between driving exposure measures and
      demographic and driving behavior variables were examined. METHODS: Respondent's
      total miles, minutes, and trips driven were calculated within a 48-hour period,
      using state-wide survey data collected in 2004 and 2005. RESULTS: The youngest
      drivers drove fewer miles and minutes, but a comparable number of trips as the
      two older groups. Employment and high vehicle access were associated with greater
      driving exposure for 16-17-year-olds and 18-24-year-olds. Employment, high
      household income, large household size, and low vehicle access were associated
      with greater driving exposure for 35-64-year-olds. More driving was done alone
      than with passengers present and during the day than at night across all ages.
      There was a positive association between two driving exposure measures (miles and
      minutes driven) and demographic and driving behavior variables, which did not
      extend to trips driven. DISCUSSION: Driving exposure is directly related to stage
      of life. The entire sample of 16-17-year-old respondents were in high school,
      which directly influenced their driving times, destinations, and purpose. Those
      aged 18-24years displayed driving behavior patterns that were closer to the older
      drivers, while retaining some differences. The oldest drivers were likely to be
      shouldering the greatest household responsibilities, and their greater driving
      exposure may reflect this reality. IMPACT ON INDUSTRY: These findings provide new
      information about driving exposure for two high-risk and one low-risk group of
      drivers. They also raise concern over potential workplace safety issues related
      to teens' higher driving exposure, and concomitant crash risk, related to being
      employed. Future research should examine this issue more carefully so that
      evidence based recommendations can be made to enhance the safety of teens who are
      employed, especially those who are employed as drivers.

PMID- 21855689
TI  - Evaluating repeated patient handling injuries following the implementation of a
      multi-factor ergonomic intervention program among health care workers.
AB  - OBJECTIVE: The objective of this study was to evaluate repeated patient handling
      injuries following a multi-factor ergonomic intervention program among health
      care workers. METHODS: This was a quasi-experimental study which had an
      intervention group and a non-randomized control group. Data were collected from
      six hospitals in Saskatchewan, Canada from September 1, 2001 to December 1, 2006.
      RESULTS: A total of 1,480 individuals who had a previous injury were eligible for
      the study. Medium and small size hospitals in the intervention group had
      significantly fewer repeated injuries than in the control group. Multivariate
      analysis showed that the intervention group had 38.1% lower odds of having
      repeated injury compared to the control group, after adjusting for hospital size.
      CONCLUSIONS: The work-related repeated injury after a multi-factor intervention
      program was reduced. The synergistic relationships between components of multi
      factor intervention and applicability of injury prevention programs to different
      settings need to be further explored. IMPACT ON INDUSTRY: Implementing a multi
      factor program with the right equipment and training can lower the risk of injury
      among health care workers.

PMID- 21855691
TI  - A framework for evaluating OSH program effectiveness using leading and trailing
      metrics.
AB  - INTRODUCTION: Many employers and regulators today rely primarily on a few past
      injury/ illness metrics as criteria for rating the effectiveness of occupational
      safety and health (OSH) programs. Although such trailing data are necessary to
      assess program success, they may not be sufficient for developing proactive
      safety, ergonomic, and medical management plans. METHODS: The goals of this pilot
      study were to create leading metrics (company self-assessment ratings) and
      trailing metrics (past loss data) that could be used to evaluate the
      effectiveness of OSH program elements that range from primary to tertiary
      prevention. The main hypothesis was that the new metrics would be explanatory
      variables for three standard future workers compensation (WC) outcomes in 2003
      (rates of total cases, lost time cases, and costs) and that the framework for
      evaluating OSH programs could be justifiably expanded. For leading metrics,
      surveys were developed to allow respondents to assess OSH exposures and program
      prevention elements (management leadership/ commitment, employee participation,
      hazard identification, hazard control, medical management, training, and program
      evaluation). After pre-testing, surveys were sent to companies covered by the
      same WC insurer in early 2003. A total of 33 completed surveys were used for
      final analysis. A series of trailing metrics were developed from 1999-2001 WC
      data for the surveyed companies. Data were analyzed using a method where each
      main 2003 WC outcome was dichotomized into high and low loss groups based on the
      median value of the variable. The mean and standard deviations of survey
      questions and 1999-2001 WC variables were compared between the dichotomized
      groups. Hypothesis testing was performed using F-test with a significance level
      0.10. RESULTS/DISCUSSION: Companies that exhibited higher musculoskeletal
      disorder (MSD) WC case rates from 1999-2001 had higher total WC case rates in
      2003. Higher levels of several self-reported OSH program elements (tracking
      progress in controlling workplace safety hazards, identifying ergonomic hazards,
      using health promotion programs) were associated with lower rates of WC lost time
      cases in 2003. Higher reported exposures to noise and projectiles were also
      associated with higher rates of WC cases and costs in 2003. IMPACT ON INDUSTRY:
      This research adds to a growing body of preliminary evidence that valid leading
      and trailing metrics can be developed to evaluate OSH effectiveness. Both the
      rating of OSH efforts and the regular trending of past loss outcomes are likely
      useful in developing data-driven improvement plans that are reactive to past
      exposures and proactive in identifying system deficiencies that drive future
      losses.

PMID- 21855692
TI  - Investigation on the role of traffic volume in accidents on urban highways.
AB  - INTRODUCTION: Roadway safety is a major concern for the general public and public
      agencies, as roadway crashes claim many lives and cause substantial economic loss
      each year. In Iran, a large number of vehicles are involved in road accidents
      each year, which cause many deaths and extensive property damage; such accidents
      are among the major causes of death and disability in the country. METHOD: To
      reduce roadway accidents, the factors that affect the occurrence and severity of
      accidents should be scrutinized to prevent or reduce their effect. The method
      that many researchers have adopted to determine the effective parameters
      surrounding road accidents in recent years is through statistical modeling of
      accidents. In this article, the role of different kinds of vehicles in traffic
      flow are investigated separately in terms of the likelihood of crashes on urban
      highways, and the vehicles are divided into three groups: passenger cars, heavy
      vehicles, and light non-passenger car vehicles. Poisson and negative binomial
      (NB) regression models were applied to model the accidents in this research,
      which were categorized into two groups: no injury (property damage only)
      accidents and more severe (injury and fatal) accidents. RESULTS: Ultimately, we
      conclude that light non-passenger car vehicles (i.e., taxis and motorcycles) play
      the largest role in the occurrence of crashes on urban highways for both types of
      accidents.

PMID- 21855693
TI  - The impact of the BP Baker report.
AB  - INTRODUCTION: This study examined the impact of the British Petroleum (BP) Baker
      Panel Report, reviewing the March 2005 BP-Texas City explosion, on the field of
      process safety. METHOD: Three hundred eighty-four subscribers of a process safety
      listserv responded to a survey two years after the BP Baker Report was published.
      RESULTS: Results revealed respondents in the field of process safety are familiar
      with the BP Baker Report, feel it is important to the future safety of chemical
      processing, and believe that the findings are generalizable to other plants
      beyond BP-Texas City. Respondents indicated that few organizations have
      administered the publicly available BP Process Safety Culture Survey. Our results
      also showed that perceptions of contractors varied depending on whether
      respondents were part of processing organizations (internal perspective) or
      government or consulting agencies (external perspective). CONCLUSIONS: This
      research provides some insight into the beliefs of chemical processing personnel
      regarding the transportability and generalizability of lessons learned from one
      organization to another. IMPACT ON INDUSTRY: This study has implications for both
      organizational scientists and engineers in that it reveals perceptions about the
      primary mechanism used to share lessons learned within one industry about one
      major catastrophe (i.e., investigation reports). This study provides preliminary
      information about the perceived impact of a report such as this one.

PMID- 21855694
TI  - Can fear of going to jail reduce the number of road fatalities? The Spanish
      experience.
AB  - The goal of this article is to evaluate the impact of the drastic Spanish Penal
      Code reform on the number of road deaths in Spain and the time that the effects
      might last. This is achieved by means of multivariate unobserved component models
      set up in a state space framework estimated using maximum likelihood. In short,
      with this reform Spain might be considered to be closing the final gap that kept
      it apart from other developed countries as far as the road accident rate is
      concerned. We have found two different types of effects on Spanish road traffic
      fatalities. Initially, a month before the reform was passed there was a 24.7
      percent fall in Spanish road deaths. After the Bill had been passed and for the
      following thirteen months, thereductionstayed at a constant sixteen percent. This
      reform has reduced Spanish road fatalities by 534 in all between November 2007
      and December 2008 and the effects will foreseeably continue during 2009.

PMID- 21855695
TI  - Obesity.

PMID- 21855696
TI  - The metabolic syndrome--from insulin resistance to obesity and diabetes.
AB  - In today's society with the escalating levels of obesity, diabetes, and
      cardiovascular disease, the metabolic syndrome is receiving considerable
      attention and is the subject of much controversy. Greater insight into the
      mechanism(s) behind the syndrome may improve our understanding of how to prevent
      and best manage this complex condition.

PMID- 21855697
TI  - Insulin resistance: the link between obesity and cardiovascular disease.
AB  - There seems to be general agreement that the prevalence of obesity is increasing
      in the United States and that we are in the midst of an obesity epidemic. The
      disease-related implications of this epidemic have received an enormous amount of
      publicity in the popular media, but public awareness of the untoward effects of
      excess weight has not led to an effective approach to dealing with the dilemma.
      The gravity of the problem is accentuated in light of the report that only
      approximately 50% of physicians polled provided weight loss counseling. Given the
      importance of excess adiposity as increasing the risk of CVD, 2DM, and
      hypertension and the combination of an increase in the prevalence of
      overweight/obesity and a health care system unprepared to deal with this
      situation, it is essential that considerable thought be given as to how to best
      address this dilemma. In this context, it must be emphasized that CVD, 2DM, and
      hypertension are characterized by resistance to insulin-mediated glucose disposal
      and that insulin resistance and the compensatory hyperinsulinemia associated with
      insulin resistance have been shown to be independent predictors of all three
      clinical syndromes. It has also been apparent for many years that
      overweight/obese individuals tend to be insulin resistant and become more insulin
      sensitive with weight loss.25 In light of these observations, it seems reasonable
      to suggest that insulin resistance is the link between overweight/obesity and the
      adverse clinical syndromes related to excess adiposity. The evidence summarized
      in this review shows that the more overweight an individual, the more likely he
      or she is insulin resistant and at increased risk to develop all the
      abnormalities associated with this defect in insulin action. Not all
      overweight/obese individuals are insulin resistant, however, any more than all
      insulin resistant individuals are overweight/obese. More important, there is
      compelling evidence that CVD risk factors are present to a significantly greater
      degree in the subset of overweight/obese individuals that is also insulin
      resistant. Not surprisingly,we have also demonstrated that an improvement in CVD
      risk factors with weight loss occurs to a significantly greater degree in those
      overweight/obese individuals who are also insulin resistant at baseline. In view
      of the ineffectiveness of current clinical approaches to weight loss, it seems
      necessary to recognize that not all overweight/obese individuals are at equal
      risk to develop CVD and that it is clinically useful to identify those at highest
      risk. The simplest way to achieve this task seems to be focusing on the CVD risk
      factors that are highly associated with insulin resistance/hyperinsulinemia. If
      this is done, then intense efforts at weight control can be brought to bear on
      those who not only need it the most but also have the most to gain by losing
      weight.

PMID- 21855698
TI  - Obesity and dyslipidemia.
AB  - Dyslipidemia associated with obesity and the metabolic syndrome is one of the
      central features contributing to the increased CV risk in these patients. In view
      of the pandemic of the metabolic syndrome, it is imperative to fully understand
      the mechanisms leading to the metabolic lipid phenotype before embarking upon
      optimal treatment strategies. The traditional concept that insulin resistance
      causes increased FFA flux via increased TG hydrolysis in adipose tissue is still
      of a central theme in the general hypothesis. The combination of increased
      hepatic VLDL secretion with impaired LPL-mediated TG clearance explains the
      hypertriglyceridemia phenotype of the metabolic syndrome. Hence, central IR may
      be an important factor contributing to peripheral hypertriglyceridemia. Recently
      recognized regulatory systems include the profound impact of the hypothalamus on
      TG secretion and glucose control. In addition, dysfunctional (or inflamed) intra
      abdominal adipose tissue has emerged as a potent regulator of dyslipidemia and
      IR. It will be a challenge to design novel treatment modalities that target
      "dysfunctional" fat or central IR to attempt to prevent the epidemic of CV
      disease secondary to the metabolic syndrome.

PMID- 21855699
TI  - Hypertension in obesity.
AB  - Obesity and HTN are on the rise in the world. HTN seems to be the most common
      obesity-related health problem and visceral obesity seems to be the major
      culprit. Unfortunately, only 31% of hypertensives are treated to goal. This
      translates into an increased incidence of CVD and related morbidity and
      mortality. Several mechanisms have been postulated as the causes of obesity
      related HTN. Activation of the RAAS, SNS, insulin resistance, leptin,
      adiponectin, dysfunctional fat, FFA, resistin, 11 Beta dehydrogenase, renal
      structural and hemodynamic changes, and OSA are some of the abnormalities in
      obesity-related HTN. Many of these factors are interrelated. Treatment of obesity
      should begin with weight loss via lifestyle modifications, medications, or
      bariatric surgery. According to the mechanisms of obesity-related HTN, it seems
      that drugs that blockade the RAAS and target the SNS should be ideal for
      treatment. There is not much evidence in the literature that one drug is better
      than another in controlling obesity-related HTN. There have only been a few
      studies specifically targeting the obese hypertensive patient, but recent trials
      that emphasize the importance of BP control have enrolled both overweight and
      obese subjects. Until we have further studies with more in-depth information
      about the mechanisms of obesity-related HTN and what the targeted treatment
      should be, the most important factor necessary to control the obesity-related HTN
      pandemic and its CVD and CKD consequences is to prevent and treat obesity and to
      treat HTN to goal.

PMID- 21855700
TI  - Impact of obesity on cardiovascular disease.
AB  - Obesity promotes a cascade of secondary pathologies including diabetes, insulin
      resistance, dyslipidemia, inflammation, thrombosis, hypertension, the metabolic
      syndrome, and OSA, which collectively heighten the risk for cardiovascular
      disease. Obesity may also be an independent moderator of cardiac risk apart from
      these comorbid conditions. Rates of obesity and cardiac disease continue to rise
      in a parallel and exponential manner. Because obesity is potentially one of the
      most modifiable mediators of cardiovascular morbidity and mortality, effective
      treatment and prevention interventions should have a profound and favorable
      impact on public health.

PMID- 21855701
TI  - The dietary treatment of obesity.
AB  - In no sector of therapeutics is the theory so simple as in weight control. The
      major gap lies in translating this theory into practice. In the final analysis,
      the answer lies in personal choice, because many diets seem to work, but not
      universally in all studies. A reduced calorie diet is obviously essential,
      although the composition remains to be individually tailored. For this, health
      care professionals must become "personal trainers" and realize the importance of
      lifestyle prescriptions with regard to diet and exercise in all consultations,
      fitting them to the needs of patient. It may be argued that medical practitioners
      do not have the necessary time or behavioral skills for these long-term
      interventions, which might be better handled by a team of other health
      professionals. Prevention is, of course, better than treatment, and therefore a
      major effort must be made to target children, from breast feeding to education
      throughout schooling. No more surveys are needed; "we know the enemy and it is
      us." In the words of the Lancet editorial concerning obesity: "Our public health
      leaders must replace prevarication with imagination."

PMID- 21855702
TI  - Exercise and the treatment of diabetes and obesity.
AB  - An active lifestyle increases general health and is protects from a number of
      different conditions, including exercise and obesity. There is emerging evidence
      that exercise by itself exerts clinically beneficial effects in both lean and
      obese subjects, even in the absence of effects on weight.1 Recent results have
      brought an increasing understanding of the molecular mechanisms underlying the
      beneficial effects of exercise at the level of metabolism and changes in gene
      expression. There is a significant dose-response to the effect of exercise, and
      the current guidelines regarding exercise amount may need to be revised upwards.
      Furthermore, this treatment option should not be overlooked.

PMID- 21855703
TI  - Cognitive and behavioral approaches in the treatment of obesity.
AB  - The research reviewed within this article provides support for both the cognitive
      and behavioral components of cognitive behavioral weight-loss interventions.
      Lifestyle based treatments have produced markedly improved results in the past 20
      years, in part attributable to changes in treatment structure. Use of
      pretreatment participant preparation strategies, extended treatment periods with
      clearly defined weight-loss goals, combining multiple dietary and physical
      activity strategies, and increasing emphasis on long-term provider contact and
      relapse prevention have modestly improved long-term weight maintenance. Several
      investigators have emphasized the need to incorporate additional cognitive
      components into the cognitive-behavioral treatment of obesity to improve both
      short- and long-term outcomes. Furthermore, continued insights into metabolic
      changes producing an energy gap after weight loss should no doubt continue to
      refine insights into the behavioral requirements of long-term weight loss.
      Despite increased awareness and behavioral treatment advances, the worldwide
      prevalence of obesity and weight-related chronic illnesses continues to expound.
      Behavioral treatment is inherently challenging and time-consuming, and readily
      available to only a fraction of the population who may benefit from inclusion.
      Several investigators have cautioned that individual or small group-based
      interventions are insufficient to serve the population masses requiring
      treatment, and that continued development of community or Web-based programs, and
      community-development tactics to increase healthy lifestyles, are needed. The
      call has been sounded to conceptualize obesity as a chronic health condition
      requiring lifelong treatment. As such, the conceptualization of cognitive
      behavioral therapies as a one-time treatment is passe' . As the current number of
      obesity specialists and behaviorally trained professionals is insufficient to
      combat this problem; an increased emphasis upon training nontraditional weight
      specialists and nonbehavioral community providers is obviated.

PMID- 21855704
TI  - Medications for weight reduction.
AB  - Comparatively few drugs are available for the treatment of overweight patients,
      and their effectiveness is limited to palliation of the chronic disease of
      obesity. Nevertheless, drug development that is now underway is more rapid than
      in the past, and we anticipate the discovery of safe and effective pharmacologic
      strategies for the management of obesity and its serious complications.

PMID- 21855705
TI  - Surgical approaches to the treatment of obesity: bariatric surgery.
AB  - As the obesity epidemic continues to grow in the Unites States, so does the
      search for the ideal nonsurgical or surgical solution. Bariatric surgery
      continues to be the most sustainable form of weight loss available to morbidly
      obese patients. In addition, bariatric surgery has established an acceptable
      safety profile with respect to morbidity and mortality. With the number of
      elective bariatric cases growing in recent years, it is unsurprising that results
      have improved and better data are emerging regarding improvement of obesity
      related comorbid conditions. Additionally, ample evidence suggests that bariatric
      surgery may increase longevity, particularly through reducing cardiovascular
      deaths. Although the specific mechanisms involved in the remission of these
      medical conditions remain to be fully elucidated, it has become clear that
      bariatric surgery has established a significant and firm role in the treatment of
      medical comorbidities that result directly from obesity. However, until
      commercial insurance carriers provide improved coverage for bariatric surgery,
      patient access to these treatments will remain limited.

PMID- 21855707
TI  - Pediatric medical home: foundations, challenges, and future directions.
AB  - The medical home concept has been in existence since the late 1960s and has
      recently been significantly broadened to encompass comprehensive primary care for
      all patient populations throughout the lifespan. This article provides (1) a
      review of the foundations and evolution of the medical home concept; (2) an
      analysis of patient/family, provider, and systemic challenges to developing an
      effective pediatric medical home particularly in relation to children's mental
      health needs; and (3) a discussion of future directions for its further adoption
      and successful implementation.

PMID- 21855708
TI  - Unexplained physical complaints.
AB  - Unexplained physical complaints are common in children and form the basis for
      childhood somatization (the manifestation of distress through somatic symptoms)
      and somatoform disorders. Emotional symptoms and anxiety disorders are often
      comorbid with both unexplained physical symptoms and somatoform disorders. Risk
      factors include stress sensibility and probably biologic vulnerability in the
      child, mood and somatization disorders in the family, parental overinvolvement,
      and possibly limited psychological "mindedness" in relation to physical symptoms.
      The best evidence of efficacy is for family behavioral cognitive treatments, but
      for especially severe cases a multidisciplinary, carefully coordinated approach
      has been found to be clinically helpful.

PMID- 21855709
TI  - Mental health concerns of the premature infant through the lifespan.
AB  - Because of increased survival rates, neurodevelopmental issues, chronic medical
      problems, and sometimes complex family issues involved with prematurity, mental
      health clinicians commonly assess preterm clients and manage their behavioral and
      mental health problems. Understanding prematurity survival and neurodevelopmental
      outcomes is important for contextualizing the mental health problems seen in this
      high-risk population. This article provides a brief overview of prematurity
      outcomes in the domains of prematurity relevant to practicing child
      psychiatrists. Prematurity is also examined as it relates to parental mental
      health challenges, infant mental health outcomes, high frequency attention
      problems, and psychiatric disorders. The complex interactions between prematurity
      and family well-being are also highlighted. Finally, evidence-based treatment
      modalities involved in prevention and management are explored.

PMID- 21855710
TI  - Psychiatric features in children with genetic syndromes: toward functional
      phenotypes.
AB  - Neurodevelopmental disorders with identified genetic etiologies present a unique
      opportunity to study gene-brain-behavior connections in child psychiatry. Parsing
      complex human behavior into dissociable components is facilitated by examining a
      relatively homogenous genetic population. As children with developmental delay
      carry a greater burden of mental illness than the general population, familiarity
      with the most common genetic disorders will serve practitioners seeing a general
      child population. In this article, basic genetic testing and 11 of the most
      common genetic disorders are reviewed, including the evidence base for treatment.
      Based on their training in child development, family systems, and multimodal
      treatment, child psychiatrists are well positioned to integrate cognitive,
      behavioral, social, psychiatric, and physical phenotypes, with a focus on
      functional impairment.

PMID- 21855711
TI  - Developmental and psychosocial issues in cystic fibrosis.
AB  - Cystic fibrosis (CF) is a multisystemic life-limiting genetic disorder, primarily
      affecting respiratory functioning. Most patients with CF are diagnosed by 2 years
      of age, and the current median predicted survival rate is 37.4 years old, with
      95% of patients dying from complications related to pulmonary infection. Given
      the chronic, progressive, and disabling nature of CF, multiple treatments are
      prescribed, most on a daily basis. Thus, this illness requires children, with the
      aid of their families, to adopt multiple health-related behaviors in addition to
      managing more typical developmental demands. The morbidity and mortality factors
      pose cognitive, emotional, and behavioral challenges for many children with CF
      and their families. This article applies a developmental perspective to
      describing the psychosocial factors affecting psychological adjustment and health
      related behaviors relevant to infants, preschool and school-age children, and
      adolescents with CF. Topics particularly pertinent to developmental periods and
      medical milestones are noted, with clinical implications highlighted.

PMID- 21855712
TI  - Psychiatric issues in pediatric organ transplantation.
AB  - Solid organ transplantation has become the first line of treatment for a growing
      number of life-threatening pediatric illnesses. With improved survival, research
      into the long-term outcome of transplant recipients has become important to
      clinicians. Adherence to medical instructions remains a challenge, particularly
      in the adolescent population. New immunosuppressant approaches promise to expand
      organ transplantation in additional directions. Extension of transplantation into
      replacement of organs such as faces and hands raises complex ethical issues.

PMID- 21855713
TI  - Inflammatory bowel disease.
AB  - This article reviews the etiology, clinical characteristics, and treatment of
      inflammatory bowel disease (IBD) and associated psychological sequelae in
      children and adolescents with this lifelong disease. Pediatric-onset IBD,
      consisting of Crohn's disease and ulcerative colitis, has significant medical
      morbidity and in many young persons is also associated with psychological and
      psychosocial challenges. Depression and anxiety are particularly prevalent and
      have a multifaceted etiology, including IBD-related factors such as cytokines and
      steroids used to treat IBD and psychosocial stress. A growing number of
      empirically supported interventions, such as cognitive behavioral therapy,
      hypnosis, and educational resources, help youth and their parents cope with IBD
      as well as the psychological and psychosocial sequelae. While there is convincing
      evidence that such interventions can help improve anxiety, depression, and health
      related quality of life, their effects on IBD severity and course await further
      study.

PMID- 21855714
TI  - Psychological considerations of the child with asthma.
AB  - Asthma, the most common chronic disease in children and adolescents in
      industrialized countries, is typified by airway inflammation and obstruction
      leading to wheezing, dyspnea, and cough. However, the effect of asthma does not
      end with pulmonary changes. Research has shown a direct link between asthma and
      stress and psychiatric illness, which if untreated results in heightened
      morbidity and effects on society. The link between asthma and psychiatric
      illness, however, is often underappreciated by many pediatric and child mental
      health professionals. This article reviews the diagnosis and treatment of asthma
      as well as the correlation between asthma and psychiatric illness in children in
      an effort to improve management and treatment strategies for this prevalent
      disease.

PMID- 21855715
TI  - The interface of child mental health and juvenile diabetes mellitus.
AB  - Diabetes mellitus is a common childhood illness, and its management is often
      complicated by mental health challenges. Psychiatric comorbidities are common,
      including anxiety, depression, and eating disorders. The illness can profoundly
      affect the developing brain and family functioning and have lifelong
      consequences. The child mental health provider can provide valuable assistance to
      support the child and family and assessment and treatment of comorbid mental
      health problems and to promote positive family functioning and normal
      developmental progress.

PMID- 21855716
TI  - Pediatric obesity: a review for the child psychiatrist.
AB  - Child and adolescent psychiatrists frequently encounter children who are obese in
      their practices and may be asked to work alongside primary care physicians and
      other specialists who treat youngsters with obesity. To offer expert
      consultation, they must understand all aspects of the pediatric obesity epidemic.
      By summarizing the relevant endocrinology, cardiology, nutrition, exercise
      science, and public health literature, this review of pediatric obesity assesses
      the epidemic's background, delineates the challenges of clinical care, and
      appraises the therapeutic recommendations for this population of patients and
      their families.

PMID- 21855717
TI  - Psychiatric concerns in pediatric epilepsy.
AB  - Pediatric epilepsy is a common, chronic, and challenging physical illness for
      children and their families. This article provides a medical overview and
      discusses the cognitive functioning and psychosocial adjustment as well as the
      psychiatric management for children and adolescents with pediatric epilepsy. The
      management of these children involves establishing a collaborative health care
      approach, evaluating academic functioning, considering psychotherapy, and
      managing psychopharmacologic treatment. A thorough understanding of the
      biopsychosocial concerns in pediatric epilepsy can enable medical providers and
      mental health clinicians to promote resiliency and adaptation in children and
      their families facing troubling seizure disorders.

PMID- 21855718
TI  - Psychiatric considerations in children and adolescents with HIV/AIDS.
AB  - The psychosocial impact of human immunodeficiency virus (HIV) disease has been
      recognized since the beginning of the epidemic for affected adults, but there has
      been less focus on the impact of HIV on young people. Among HIV-positive (HIV+)
      adults, high levels of distress, psychiatric symptoms, and their associations
      with worse health outcomes were recognized early in the epidemic. Subsequently,
      many studies have focused on understanding the prevalence of psychiatric symptoms
      among HIV+ adults and on identifying effective treatments for these symptoms.
      Fewer studies have examined these symptoms and their treatments among HIV+
      children and adolescents. This article reviews what is known about psychiatric
      syndromes among HIV+ youths, their treatments, and other psychosocial factors of
      concern to the psychiatrist when treating children and adolescents with HIV
      disease.

PMID- 21855719
TI  - Psychiatric aspects of pediatric cancer.
AB  - The diagnosis and treatment of children and adolescents with cancer has a
      tremendous and lasting effect on the patients, their families, and other
      individuals in their social network. It carries a host of psychological and
      behavioral ramifications, from questions of mortality to changes in levels of
      functioning in multiple domains. In this review the authors address the
      psychosocial and treatment-related issues that arise in children with cancer,
      with attention to the adjustment to cancer at different developmental stages,
      mood and anxiety issues, treatment-related psychiatric sequelae, and the
      challenges faced by childhood cancer survivors.

PMID- 21855720
TI  - Partnerships between pediatric palliative care and psychiatry.
AB  - Children with life-threatening illnesses and their families may face physical,
      emotional, psychosocial, and spiritual challenges throughout the children's
      course of illness. Pediatric palliative care is designed to meet such challenges.
      Given the psychosocial and emotional needs of children and their families it is
      clear that psychiatrists can, and do, play a role in delivering pediatric
      palliative care. In this article the partnership between pediatric palliative
      care and psychiatry is explored. The authors present an overview of pediatric
      palliative care followed by a summary of some of the roles for psychiatry. Two
      innovative pediatric palliative care programs that psychiatrists may or may not
      be aware of are described. Finally, some challenges that are faced in further
      developing this partnership and suggestions for future research are discussed.

PMID- 21855721
TI  - Advances in dermatologic diagnosis, Part II.

PMID- 21855722
TI  - Opportunistic localization of skin lesions on vulnerable areas.
AB  - Genetic, developmental, and immune defects can make certain anatomic areas of the
      body more prone than others to harbor skin lesions. Cutaneous areas with skin
      barrier dysfunction (eg, atopic dermatitis) are the clearest example of
      vulnerable sites where opportunistic diseases, mainly infections (eg, herpes
      simplex), can easily occur. Somatic mosaicism, by giving rise to mutated cell
      clones with a bandlike arrangement, may form tissue segments prone to developing
      congenital or acquired skin disorders. Cutaneous districts that have been
      infected by herpes viruses become sites permissive for a subsequent onset of
      heterogeneous skin disorders, mainly tumors, further infections, and disimmune
      reactions (Wolf isotopic response). Regional lymphedema, by impairing lymph
      circulation and consequently the local immune control, favors the location of
      immunity-related lesions in the involved district. A vast series of skin
      injuries, such as ionizing or ultraviolet radiation, burns, traumas, and even
      vaccinations, can render the affected areas vulnerable to subsequent cutaneous
      disorders. Lack of immune control, ensuing from locally altered neuroimmune
      interaction, may be the basic defect responsible for the opportunistic location
      of skin lesions in herpes-infected, lymphedematous, or otherwise damaged areas,
      together featuring the novel concept of "immunocompromised district."

PMID- 21855723
TI  - Differential diagnosis of round or discoid lesions.
AB  - Dermatologists are called on to diagnose a variety of skin conditions in diverse
      age groups. Dermatologic diagnosis, based on identification of a primary lesion,
      uses morphologic clues to categorize the pathologic process causing the eruption.
      In addition, distribution and grouping of lesions helps support a specific
      diagnosis. Dermatologists consciously or unconsciously use pattern recognition to
      arrive at their differential diagnosis based on clinical experience and their
      having previously viewed similarly appearing skin lesions in lectures, texts, and
      journals. Round and discoid patches and plaques are extremely common in the
      clinical practice of dermatology. This contribution reviews the dermatologic
      conditions that present as round or discoid lesions and presents an approach to
      diagnosis.

PMID- 21855724
TI  - Patterned disorders in dermatology.
AB  - The skin gives us an opportunity to study pathologies unapparent in other systems
      such as patterned disorders. Among the best-identified patterns of skin disorders
      are the well-known lines of Blaschko, but other types of skin-patterned lesions
      have also been recognized. This short review will describe and discuss these
      different patterns and their pathophysiologic mechanisms, such as somatic
      mosaicism and X-chromosome associated mosaicism. Cutaneous patterned disorders
      are thought to be associated usually with inherited diseases per se, but in fact
      they are also reported in so-called acquired diseases. These cases suggest the
      existence of an underlying defect in a gene closely associated with the disease
      pathogenesis. The study of these acquired patterned disorders in the future may
      help us to understand the biologic foundations and pathogenesis of common human
      diseases.

PMID- 21855725
TI  - Shape and configuration of skin lesions: targetoid lesions.
AB  - What is probably the first description of targetoid or iris lesions, as they
      appear in erythema multiforme (EM), can be found in Thomas Bateman's 1836
      textbook "Practical Synopsis of Cutaneous Diseases According to the Arrangement
      of Dr. Willan." EM was initially described by Bateman and later by von Hebra as
      an acute self-limiting skin disease, symmetrically distributed on the extremities
      with typical concentric "targetoid" or "iris" lesions, and often recurrent.
      Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were added to
      this syndrome later. A newer classification has created two disease spectra: EM
      consisting of EM minor and EM major (or bullous EM), and SJS and TEN. EM minor
      and EM major are often recurrent, postinfectious (especially after herpes and
      mycoplasma) disorders with low morbidity and almost no mortality. SJS and TEN are
      usually severe drug-induced reactions with high morbidity and poor prognosis. The
      target lesions found in each form of the disease are described and defined.
      Although the term "target lesion" originated from the description of EM and
      despite its being the dominant lesion in this disease, it is not pathognomonic
      for EM, and these lesions can sometimes appear in other diseases. Short
      descriptions of these other diseases are presented.

PMID- 21855726
TI  - Shape and configuration of skin lesions: grouped herpetiform.
AB  - Lesions that may present in a grouped way include diseases with grouped vesicles
      such as dyshidrosis, nummular dermatitis, herpes simplex, and herpes zoster;
      diseases with grouped vesicobullae such as dermatitis herpetiformis, herpes
      gestationis, subacute lupus erythematosus in the bullous variant, and pemphigus
      herpetiformis; and diseases with grouped pustules such as pustular psoriasis,
      dermatitis continua of Hallopeau, and impetigo herpetiformis.

PMID- 21855727
TI  - Cutaneous signs of systemic disease.
AB  - Commonly used dermatologic eponyms and characteristic skin signs are enormously
      helpful in guiding a diagnosis, even though they may not be pathonemonic. They
      include, on the nails, Aldrich-Mees' lines (syn.: Mees' lines), Beau's lines,
      Muehrcke's lines, Terry's nails, and half and half nails, often associated,
      respectively, with arsenic poisoning, acute stress or systemic illness, severe
      hypertension, liver disease and uremia, and, around the nails, Braverman's sign,
      associated with collagen-vascular disease. Elsewhere, one may see the Asboe
      Hansen and Nikolsky's signs, indicative of the pemphigus group of diseases,
      Auspitz's sign, a classic finding in psoriasis, Borsieri's and Pasita's signs,
      seen in early scarlet fever, the butterfly rash, indicative of systemic lupus
      erythematosus, and the buffalo hump, seen in Cushing's disease and also in the
      more common corticosteroid toxicity. Gottron's papules and the heliotrope rash
      are signs of dermatomyositis. Janeway's lesions and Osler's nodes are seen in
      bacterial endocarditis. A Dennie-Morgan fold under the eye is seen in association
      with atopic disease. Koplik's spots are an early sign of rubeola. Fitzpatrick's
      sign is indicative of a benign lesion (dermatofibroma), whereas Hutchinson's sign
      is indicative of a malignant one (subungual melanoma). Petechiae are seen in many
      diseases, including fat embolization, particularly from a large bone fracture
      following trauma. Palpable purpura is indicative of leukocytoclastic vasculitis,
      and is an early, critical sign in Rickettsial diseases, including Rocky Mountain
      Spotted Fever, which must be diagnosed and treated early. Hyperpigmentation of
      areolae and scars is seen in Addison's disease. Acanthosis nigricans may indicate
      internal cancer, especially stomach cancer, whereas Bazex's syndrome occurs in
      synchrony with primary, usually squamous cancer, in the upper aerodigestive tract
      or metastatic cancer in cervical lymph nodes. Perioral pigmented macules or one
      or more cutaneous sebaceous neoplasms may be a sign of the Peutz-Jeghers or Muir
      Torre syndrome, respectively, both associated also with intestinal polyps that
      have a malignant potential. Telangiectasiae in the perioral region may be
      associated with similar lesions internally in Osler-Weber-Rendu disease. Kerr's
      sign is indicative of spinal cord injury and Darier's sign of mastocytosis. Post
      proctoscopic periobital purpura (PPPP) is a phenomenon observed in some patients
      with systemic amyloidosis. Koebner's isomorphic response refers to the tendency
      of an established dermatosis, such as psoriasis, to arise in (a) site(s) of
      trauma, whereas Wolf's isotrophic response refers to a new dermatosis, such as
      tinea, not yet seen in the patient, arising in (a) site(s) of a former but
      different dermatosis, such as zoster.

PMID- 21855728
TI  - Mnemonics in dermatology.
AB  - An Internet search has provided many examples of mnemonics. These are readily
      available, so we thought of composing new mnemonics that included information
      about the authors who first described the disease or are associated with the
      disease in question. We found this a pleasurable experience, because one of the
      authors (C.S.) either knew or knew of many of those who were responsible for the
      first writing of the diseases.

PMID- 21855729
TI  - Skin signs of systemic diseases.
AB  - The skin should not be considered as an isolated organ but rather as a definite
      functioning system that communicates with the internal environment. Skin signs of
      systemic diseases occur frequently and sometimes feature the first symptoms of an
      internal disease; furthermore, these manifestations may be the sole expressions
      of otherwise asymptomatic systemic disorders. A number of dermatologic signs,
      symptoms, and disorders can be invaluable as markers of systemic disease.
      Although a plethora of specialized modern diagnostic tests are available, the
      skin still remains the only organ of the body that is immediately and completely
      accessible to direct clinical examination. This contribution reviews the skin
      signs of systemic diseases. The description of the clinical features of skin
      lesions observed in several internal diseases will be useful to general
      physicians, internists, and dermatologists in the diagnosis of a systemic
      disease.

PMID- 21855731
TI  - Diagnostic procedures in dermatology.
AB  - Although most skin diseases can be diagnosed with simple visual inspection,
      laboratory investigations are necessary in several clinical circumstances. This
      contribution highlights the usefulness of routine diagnostic procedures that are
      often overlooked and the innovative methods of molecular biology, which are
      expensive and require an experienced staff. Among the classic diagnostic
      investigations are (1) the use of Wood's light in many dermatologic disorders
      (eg, vitiligo, pityriasis versicolor, erythrasma, porphyrias), (2) cytodiagnosis
      of Tzanck in dermatologic practice (eg, herpetic infections, molluscum
      contagiosum, leishmaniasis, pemphigus vulgaris, basal cell carcinoma,
      erythroplasia of Queyrat, Hailey-Hailey disease), and (3) microscopic examination
      for fungal and bacterial skin infections as well as for mite infestation using
      potassium hydroxide, simple saline, and Gram stain. Modern molecular
      biotechnologies encompassing gene-specific polymerase chain reaction and its
      variants have a substantial affect in selected cases of viral (especially herpes
      simplex virus), bacterial, fungal, and protozoan (Leishmania) skin infections.

PMID- 21855730
TI  - Cutaneous paraneoplasia.
AB  - Paraneoplasias are frequently the first sign of a subjacent malignant tumor.
      Although relatively rare, they need to be recognized by dermatologists to make an
      early diagnosis and improve the prognosis related especially to the neoplasia.
      This contribution presents the morphologic aspects and the differential diagnosis
      of the main paraneoplasias, which include acanthosis nigricans, tripe palms,
      Leser-Trelat sign, acquired ichthyosis, acquired hypertrichosis lanuginosa,
      pityriasis rotunda, erythema gyratum repens, palmo-plantar keratoderma, Bazex
      syndrome, and dermatomyositis, hoping to contribute to the familiarity of
      dermatologists with the identification and early diagnosis of this group.

PMID- 21855732
TI  - Dermatoscopy: an overview of subsurface morphology.
AB  - Within the past two decades, an exponential number of publications have emerged
      on the topic of dermatoscopy, most, if not all, reporting the benefits of using a
      dermatoscope. Dermatoscopy has been promoted to be useful in diagnosing not only
      pigmented skin lesions but also a wide range of skin conditions that are
      infectious, hamartomatous, and inflammatory in nature. Whether or not
      dermatoscopy truly has a relevant diagnostic role in such a wide range of skin
      conditions remains to be proven. The diagnostic technique, however, has
      fundamentally changed the way pigmented lesions are evaluated by dermatologists,
      as it offers a more methodical and disciplined approach to evaluate them. This
      review highlights the contribution of dermatoscopy with respect to morphologic
      characterization and evaluation of pigmented skin lesions.

PMID- 21855733
TI  - Maimonides: part 2--his philosophy and his contribution to medicine.

PMID- 21855734
TI  - Bibliography of secondary sources on the history of dermatology: II. Obituaries
      and biographies in English supplemented through 2010.

PMID- 21855735
TI  - The ONQI is not a black box.

PMID- 21855737
TI  - Active travel in Germany and the U.S. Contributions of daily walking and cycling
      to physical activity.
AB  - BACKGROUND: Travel surveys in Europe and the U.S. show large differences in the
      proportion of walking and cycling trips without considering implications for
      physical activity. PURPOSE: This study estimates differences between Germany and
      the U.S. over time in population levels of daily walking and cycling at different
      health-enhancing thresholds across sociodemographic groups. METHODS: Uniquely
      comparable national travel surveys for the U.S. (NHTS 2001 and 2009) and Germany
      (MiD 2002 and 2008) were used to calculate the number, duration, and distance of
      active trips per capita. The population-weighted person and trip files for each
      survey were merged to calculate population levels of any walking/cycling,
      walking/cycling 30 minutes/day, and achieving 30 minutes in bouts of at least 10
      minutes. Logistic regression models controlled for the influence of socioeconomic
      variables. Data were analyzed in 2010. RESULTS: Between 2001/2002 and 2008/2009,
      the proportion of "any walking" was stable in the U.S. (18.5%) but increased in
      Germany from 36.5% to 42.3%. The proportion of "any cycling" in the U.S. remained
      at 1.8% but increased in Germany from 12.1% to 14.1%. In 2008/2009, the
      proportion of "30 minutes of walking and cycling" in Germany was 21.2% and 7.8%,
      respectively, compared to 7.7% and 1.0% in the U.S. There is much less variation
      in active travel among socioeconomic groups in Germany than in the U.S. German
      women, children, and seniors walk and cycle much more than their counterparts in
      the U.S. CONCLUSIONS: The high prevalence of active travel in Germany shows that
      daily walking and cycling can help a large proportion of the population to meet
      recommended physical activity levels.

PMID- 21855739
TI  - Park-based physical activity among children and adolescents.
AB  - BACKGROUND: Availability of parks is associated with higher levels of physical
      activity among children and adolescents. Few studies examine actual park use and
      park-based physical activity in these populations. PURPOSE: This study examined
      associations among individual, park, and neighborhood environmental
      characteristics and children's and adolescent's park-based physical activity.
      METHODS: Data were collected in 2007 on 2712 children in 20 randomly selected
      parks in Durham NC. The System for Observing Play and Recreation in Communities
      (SOPARC) provided measures of physical activity. Hierarchic regression analysis
      assessed associations among individual, park, and neighborhood environmental
      characteristics and children's park-based physical activity. Data were analyzed
      in 2010. RESULTS: Of the 2712 children observed, 34.2% and 13.2% were engaged in
      walking or vigorous physical activity. Environmental features of parks were
      associated with activity levels whereas neighborhood characteristics were not.
      Physical activity was negatively associated with gender (girls) (p=0.003);
      presence of a parent (p<0.0001); presence of nonparental adult (p=0.006); and an
      interaction involving the 0-5 years age group and style of play (p=0.017). Higher
      level of physical activity was associated with presence of other active children
      (p<0.0001); courts (e.g., basketball); and an interaction between number of
      recreation facilities and formal activities (p=0.004). CONCLUSIONS: These social
      factors and design features should be considered in order to stimulate higher
      levels of park-based physical activity among children and adolescents.

PMID- 21855738
TI  - Modeling of regional climate change effects on ground-level ozone and childhood
      asthma.
AB  - BACKGROUND: The adverse respiratory effects of ground-level ozone are well
      established. Ozone is the air pollutant most consistently projected to increase
      under future climate change. PURPOSE: To project future pediatric asthma
      emergency department visits associated with ground-level ozone changes, comparing
      1990s to 2020s. METHODS: This study assessed future numbers of asthma emergency
      department visits for children aged 0-17 years using (1) baseline New York City
      metropolitan area emergency department rates; (2) a dose-response relationship
      between ozone levels and pediatric asthma emergency department visits; and (3)
      projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by
      a global-to-regional climate change and atmospheric chemistry model. Sensitivity
      analyses included population projections and ozone precursor changes. This
      analysis occurred in 2010. RESULTS: In this model, climate change could cause an
      increase in regional summer ozone-related asthma emergency department visits for
      children aged 0-17 years of 7.3% across the New York City metropolitan region by
      the 2020s. This effect diminished with inclusion of ozone precursor changes. When
      population growth is included, the projections of morbidity related to ozone are
      even larger. CONCLUSIONS: The results of this analysis demonstrate that the use
      of regional climate and atmospheric chemistry models make possible the projection
      of local climate change health effects for specific age groups and specific
      disease outcomes, such as emergency department visits for asthma. Efforts should
      be made to improve on this type of modeling to inform local and wider-scale
      climate change mitigation and adaptation policy.

PMID- 21855740
TI  - Neighborhood socioeconomic status and leisure-time physical activity after
      myocardial infarction: A longitudinal study.
AB  - BACKGROUND: Area-level SES is independently associated with myocardial infarction
      (MI) prognosis, yet the mechanisms for this association remain speculative.
      PURPOSE: Using a population-based cohort of MI patients, this study examined
      whether neighborhood SES predicts long-term trajectory of leisure-time physical
      activity (LTPA), an established prognostic factor. METHODS: Patients aged <=65
      years (n=1410) admitted to hospital in central Israel with first MI in 1992-1993,
      were followed up through 2005. LTPA was reported on five successive occasions: at
      baseline, 3-6 months, 1-2 years, 5 years, and 10-13 years post-MI. Generalized
      estimating equations (GEEs) with ordinal outcome variable (LTPA classified as
      regular, irregular, or none) were used to determine the independent predictive
      role of neighborhood SES in LTPA trajectory post-MI. Analyses were conducted in
      2010-2011. RESULTS: Engagement in LTPA was poor, with point prevalence rates
      ranging from 33% to 37% for inactivity and from 19% to 27% for irregular activity
      throughout follow-up. The GEE-derived ORs (95% CIs) for decreased LTPA level in
      the lower and middle vs upper neighborhood SES tertiles were 2.49 (2.05, 3.02)
      and 1.60 (1.33, 1.92) after age and gender adjustment, and 1.55 (1.26, 1.90) and
      1.23 (1.02, 1.49) after multivariable adjustment for individual SES measures,
      cardiovascular risk factors, MI characteristics, and disease-severity indices,
      respectively (p for trend <0.001). CONCLUSIONS: Low neighborhood SES is a
      powerful predictor of poor LTPA uptake in MI survivors, even after extensive
      adjustment for individual SES and baseline clinical profile. LTPA may thus
      represent an intermediate mechanism between neighborhood SES and post-MI outcome,
      which provides prevention opportunities.

PMID- 21855741
TI  - Maintenance of exercise after phase II cardiac rehabilitation: a randomized
      controlled trial.
AB  - BACKGROUND: Patients who have completed Phase II cardiac rehabilitation have low
      rates of maintenance of exercise after program completion, despite the importance
      of sustaining regular exercise to prevent future cardiac events. PURPOSE: The
      efficacy of a home-based intervention to support exercise maintenance among
      patients who had completed Phase II cardiac rehabilitation versus contact control
      was evaluated. DESIGN: An RCT was used to evaluate the intervention. Data were
      collected in 2005-2010 and analyzed in 2010. SETTING/PARTICIPANTS: One hundred
      thirty patients (mean age=63.6 years [SD=9.7], 20.8% female) were randomized to
      exercise counseling (Maintenance Counseling group, n=64) or contact control
      (Contact Control group, n=66). INTERVENTION: Maintenance Counseling group
      participants received a 6-month program of exercise counseling (based on the
      transtheoretical model and social cognitive theory) delivered via telephone, as
      well as print materials and feedback reports. MAIN OUTCOME MEASURES: Assessments
      of physical activity (7-Day Physical Activity Recall), motivational readiness for
      exercise, lipids, and physical functioning were conducted at baseline, 6 months,
      and 12 months. Objective accelerometer data were collected at the same time
      points. Fitness was assessed via maximal exercise stress tests at baseline and 6
      months. RESULTS: The Maintenance Counseling group reported significantly higher
      exercise participation than the Contact Control group at 12 months (difference of
      80 minutes, 95% CI=22, 137). Group differences in exercise at 6 months were
      nonsignificant. The intervention significantly increased the probability of
      participants' exercising at or above physical activity guidelines and attenuated
      regression in motivational readiness versus the Contact Control Group at 6 and 12
      months. Self-reported physical functioning was significantly higher in the
      Maintenance Counseling group at 12 months. No group differences were seen in
      fitness at 6 months or lipid measures at 6 and 12 months. CONCLUSIONS: A
      telephone-based intervention can help maintain exercise, prevent regression in
      motivational readiness for exercise, and improve physical functioning in this
      patient population.

PMID- 21855742
TI  - Self-regulatory processes and exercise adherence in older adults: executive
      function and self-efficacy effects.
AB  - BACKGROUND: Self-efficacy and the use of self-regulatory strategies are
      consistently associated with physical activity behavior. Similarly, behavioral
      inhibition and cognitive resource allocation-indices of executive control
      function-have also been associated with this health behavior. PURPOSE: The
      purpose of this study was to examine the hypothesis that self-efficacy mediates
      the relationship between self-regulatory processes, such as executive function,
      and sustained exercise behavior. METHODS: Older adults (N=177, mean age=66.44
      years) completed measures of executive function, self-reported use of self
      regulatory strategies, and self-efficacy prior to and during the first month of a
      12-month exercise intervention. Percentage of exercise classes attended over the
      following 11 months was used to represent adherence. Data were collected from
      2007 to 2010 and analyzed in 2010-2011. Structural equation models were tested
      examining the effect of executive function and strategy use on adherence via
      efficacy. RESULTS: As hypothesized, results showed significant direct effects of
      two elements of executive function and of strategy use on self-efficacy and of
      efficacy on adherence. In addition, there were significant indirect effects of
      strategy use and executive function on adherence via self-efficacy. CONCLUSIONS:
      Higher levels of executive function and use of self-regulatory strategies at the
      start of an exercise program enhance beliefs in exercise capabilities, which in
      turn leads to greater adherence.

PMID- 21855743
TI  - Child and adolescent exposure to food and beverage brand appearances during prime
      time television programming.
AB  - BACKGROUND: The food industry disproportionately markets to young people through
      product placements. Children and adolescents may be more susceptible to these
      disguised persuasive attempts. PURPOSE: Quantify incidence and youth exposure to
      food and beverage brand appearances within shows on prime-time TV. METHODS: Data
      on the number of food, beverage, and restaurant brand appearances within shows
      during prime-time programming in 2008 were purchased from Nielsen and analyzed by
      product category and company in 2010. Exposure to these brand appearances by
      children, adolescents, and adults were examined and compared with exposure to
      prime-time TV advertisements for the same categories and companies using
      additional Nielsen data. RESULTS: Food, beverage, and restaurant brands appeared
      a total of 35,000 times within prime-time TV programming examined by Nielsen in
      2008. Regular soft drinks, traditional restaurants (i.e., not quickserve), and
      energy/sports drinks made up 60% of all brand appearances. Young people viewed
      relatively few of these appearances with one notable exception. Coca-Cola
      products were seen 198 times by the average child and 269 times by the average
      adolescent during prime-time shows over the year, accounting for 70% of child
      exposure and 61% of adolescent exposure to brand appearances. One show, American
      Idol, accounted for more than 95% of these exposures. Exposure of children to
      Coca-Cola products through traditional advertisements was much less common.
      CONCLUSIONS: Brand appearances for most food industry companies, except for Coca
      Cola, are relatively rare during prime-time programming with large youth
      audiences. Coca-Cola has pledged to refrain from advertising to children, yet the
      average child views almost four Coke appearances on prime-time TV every week.
      This analysis reveals a substantial, potential loophole in current food industry
      self-regulatory pledges to advertise only better-for-you foods to children.

PMID- 21855744
TI  - Cigarettes smoked per day among high school students in the U.S., 1991-2009.
AB  - BACKGROUND: Recent declines in current cigarette smoking among youth are
      encouraging, but less is known about the trends in the number of cigarettes
      smoked per day among youth. PURPOSE: This study examined trends in the number of
      cigarettes smoked per day among U.S. high school students during 1991-2009.
      METHODS: Nationally representative data from the 1991-2009 national Youth Risk
      Behavior Surveys (YRBS) were analyzed in 2010. The YRBS is a biennial, school
      based survey representative of 9th- through 12th-grade students in the U.S. Each
      survey year, students completed anonymous, self-administered questionnaires that
      included identically worded questions about cigarette use. The number of
      cigarettes smoked per day on smoking days was categorized as light smoking (<1-5
      cigarettes per day); moderate smoking (6-10 cigarettes per day); and heavy
      smoking (>=11 cigarettes per day). Sample sizes ranged from 10,904 to 16,410.
      Overall response rates ranged from 60% to 71%. RESULTS: During 1991-2009, among
      current cigarette users overall, light smoking increased from 67.2% to 79.4% and
      heavy smoking decreased from 18.0% to 7.8%. These trends were found among female
      and male students overall and white students. Among Hispanic students, light
      smoking remained stable, but heavy smoking significantly increased from 3.1% in
      1991 to 6.4% in 2009. The prevalence of light, moderate, and heavy smoking did
      not change during 1991-2009 among black students. CONCLUSIONS: The finding that
      during 1991-2009 light smoking increased and heavy smoking decreased among
      current cigarette users is encouraging; however, even light smoking is
      detrimental to health and efforts to reduce all cigarette use should continue.

PMID- 21855745
TI  - Evaluation of an Internet-based alcohol misuse prevention course for college
      freshmen: findings of a randomized multi-campus trial.
AB  - BACKGROUND: Internet-based alcohol misuse prevention programs are now used by
      many universities. One popular 2- to 3-hour online course known as AlcoholEdu for
      College is typically required for all incoming freshmen and thus constitutes a
      campus-level strategy to reduce student alcohol misuse. PURPOSE: Multi-campus
      study to evaluate the effectiveness of an Internet-based alcohol misuse
      prevention course. DESIGN: RCT with 30 universities: 21 entered the study in Fall
      2007, nine in Fall 2008. Fifteen were randomly assigned to receive the online
      course and the other 15 were assigned to the control condition. The course was
      implemented by intervention schools during the late summer and/or fall semester.
      Cross-sectional surveys of freshmen were conducted at each university, beginning
      prior to the intervention in Spring 2008-2009; post-intervention surveys were
      administered in Fall 2008-2009 and Spring 2009-2010. SETTING/PARTICIPANTS: Public
      and private universities of varying sizes across the U.S. Random samples of 200
      freshmen per campus were invited to participate in online surveys for the
      evaluation. Overall survey response rates ranged from 44% to 48% (M ~ 90
      participants per campus). INTERVENTION: The online course includes five modules;
      the first four (Part I) are typically offered in the late summer before
      matriculation, and the fifth (Part II) in early fall. Course content includes
      defining a standard drink, physiologic effects of alcohol, the need to monitor
      blood alcohol level, social influences on alcohol use, alcohol laws, personalized
      normative feedback, and alcohol harm-reduction strategies. Students must pass an
      exam after Part I to advance to Part II. MAIN OUTCOME MEASURES: Past-30-day
      alcohol use, average number of drinks per occasion, and binge drinking. RESULTS:
      Multilevel intent-to-treat analyses indicated significant reductions in the
      frequency of past-30-day alcohol use (beta = -0.64, p<0.05) and binge drinking
      (beta = -0.26, p<0.05) during the fall semester immediately after completion of
      the course. However, these effects did not persist when assessed in the spring
      semester. Post hoc comparisons suggested stronger course effects on these
      outcomes at colleges with higher rates of student course completion. No course
      effects were observed for average number of drinks per occasion or prevalence of
      binge drinking, regardless of the campus course completion rate. CONCLUSIONS:
      This study provides initial evidence that the Internet-based alcohol misuse
      prevention course has beneficial short-term effects on hazardous drinking
      behavior among first-year college students, which should be reinforced through
      effective environmental prevention strategies.

PMID- 21855746
TI  - Motivating public school districts to adopt sun protection policies: a randomized
      controlled trial.
AB  - BACKGROUND: In 2002, CDC recommended that the nation's schools establish policies
      that reduce sun exposure to decrease students' risk of skin cancer. PURPOSE: A
      program to convince public school districts to adopt such a policy was evaluated.
      DESIGN: RCT. SETTING/PARTICIPANTS: Public school districts in Colorado (n=56) and
      Southern California (n=56). INTERVENTION: Policy information, tools, and
      technical assistance were provided through printed materials, a website, meetings
      with administrators, and presentations to school boards. An RCT enrolled public
      school districts from 2005 to 2010. Policy adoption was promoted over 2 years at
      districts randomized to the intervention. MAIN OUTCOME MEASURES: School board
      approved policies were obtained from 106 districts and coded at baseline and 2
      year follow-up. Analyses were conducted in 2010. RESULTS: There was no difference
      in the percentage of districts adopting a policy (24% in intervention; 12% in
      control; p=0.142); however, intervention districts (adjusted M=3.10 of 21 total
      score) adopted stronger sun safety policies than control districts (adjusted
      M=1.79; p=0.035). Policy categories improved on sun safety education for students
      (intervention adjusted M=0.76; control adjusted M=0.43, p=0.048); provision of
      outdoor shade (intervention adjusted M=0.79; control adjusted M=0.28, p=0.029);
      and outreach to parents (intervention adjusted M=0.59; control adjusted M=0.20,
      p=0.027). CONCLUSIONS: Multifaceted promotion can increase adoption of stronger
      policies for reducing sun exposure of students by public school districts. Future
      research should explore how policies are implemented by schools.

PMID- 21855747
TI  - Adherence to the Advisory Committee on Immunization Practices recommendation to
      prevent injuries from postvaccination syncope: a national physician survey.
AB  - BACKGROUND: Little is known about physicians' adherence to the 2006 Advisory
      Committee on Immunization Practices (ACIP) recommendation that providers strongly
      should consider observing vaccine recipients for 15 minutes to prevent injuries
      from postvaccination syncope. PURPOSE: To assess physicians' knowledge,
      attitudes, and practices toward observing adolescents for 15 minutes
      postvaccination. METHODS: A survey was administered during October 2008-January
      2009 to 425 pediatricians (Peds) and 424 family medicine physicians (FPs) from a
      nationally representative network. Adherence was defined as reporting routinely
      observing patients for >=15 minutes after vaccination. Data analysis was
      completed in 2009. RESULTS: The overall response rate was 73%. A minority of
      physicians (37% Peds, 24% FPs) were aware that ACIP strongly encourages observing
      patients for 15 minutes postvaccination, but most physicians (69% Peds, 84% FPs)
      thought that their practice easily could adhere to this recommendation. Lack of
      room space (76% Peds, 65% FPs) was the most frequently reported barrier.
      Seventeen percent of physicians reported adherence to postvaccination
      observation. Practice in a hospital, university, or community health center
      compared with private practice (RR=1.64, 95% CI=1.05, 2.40); awareness of the
      ACIP syncope recommendation (RR=5.55, 95% CI=3.60, 9.37); and believing that
      postvaccination syncope can result in serious injuries (RR=1.74, 95% CI=1.06,
      4.22) were independently associated with self-reported adherence. CONCLUSIONS:
      Few physicians are aware of recommendations for postvaccination observation for
      syncope and even fewer adhere to them. Strategies to improve this should be
      developed and tested.

PMID- 21855748
TI  - Industry progress to market a healthful diet to American children and
      adolescents.
AB  - CONTEXT: The IOM released an expert committee report in 2005 that assessed the
      nature, extent, and influence of food and beverage marketing practices on the
      diets and health of American children and adolescents. The report concluded that
      prevailing marketing practices did not support a healthful diet and offered
      recommendations for diverse stakeholders to promote a healthful diet. The
      investigators evaluated progress made by food, beverage, and restaurant
      companies; trade associations; entertainment companies; and the media to achieve
      the IOM report recommendations over 5 years. EVIDENCE ACQUISITION: A literature
      review was conducted of electronic databases and relevant government, industry,
      and media websites between December 1, 2005, and January 31, 2011. Evidence
      selection was guided by the IOM LEAD principles (i.e., locate, evaluate, and
      assemble evidence to inform decisions) and five qualitative-research criteria,
      and it was validated by data and investigator triangulation. The investigators
      selected and categorized 117 data sources into two evidence tables used to
      evaluate industry progress (i.e., no, limited, moderate, and extensive). EVIDENCE
      SYNTHESIS: Food and beverage companies made moderate progress; however, limited
      progress was made by other industry subsectors. Industry stakeholders used
      integrated marketing communications (IMC) to promote primarily unhealthy
      products, which threaten children's and adolescents' health and miss
      opportunities to promote a healthy eating environment. CONCLUSIONS: Diverse
      industry stakeholders have several untapped opportunities to advance progress by
      promoting IMC to support a healthful diet; substantially strengthening self
      regulatory programs; supporting truthful and non-misleading product labeling and
      health claims; engaging in partnerships; and funding independent evaluations of
      collective efforts.

PMID- 21855750
TI  - Recommendations on dram shop liability and overservice law enforcement
      initiatives to prevent excessive alcohol consumption and related harms.
AB  - The Task Force on Community Preventive Services recommends the use of dram shop
      liability laws, on the basis of strong evidence of effectiveness in preventing
      and reducing alcohol-related harms. The Task Force found insufficient evidence to
      determine the effectiveness of overservice law enforcement initiatives as a means
      to reduce excessive alcohol consumption and related harms, because too few
      studies were identified and findings were inconsistent.

PMID- 21855751
TI  - Effects of dram shop liability and enhanced overservice law enforcement
      initiatives on excessive alcohol consumption and related harms, a commentary on a
      New Mexico perspective.

PMID- 21855749
TI  - Effects of dram shop liability and enhanced overservice law enforcement
      initiatives on excessive alcohol consumption and related harms: Two community
      guide systematic reviews.
AB  - CONTEXT: Dram shop liability holds the owner or server(s) at a bar, restaurant,
      or other location where a patron, adult or underage, consumed his or her last
      alcoholic beverage responsible for harms subsequently inflicted by the patron on
      others. Liability in a state can be established by case law or statute.
      Overservice laws prohibit the sale of alcoholic beverages to intoxicated patrons
      drinking in on-premises retail alcohol outlets (i.e., premises where the alcohol
      is consumed where purchased); enhanced enforcement of these laws is intended to
      ensure compliance by premises personnel. Both of these interventions are
      ultimately designed to promote responsible beverage service by reducing sales to
      intoxicated patrons, underage youth, or both. This review assesses the
      effectiveness of dram shop liability and the enhanced enforcement of overservice
      laws for preventing excessive alcohol consumption and related harms. EVIDENCE
      ACQUISITION: Studies assessing alcohol-related harms in states adopting dram shop
      laws were evaluated, as were studies assessing alcohol-related harms in regions
      with enhanced overservice enforcement. Methods previously developed for
      systematic reviews for the Guide to Community Preventive Services were used.
      EVIDENCE SYNTHESIS: Eleven studies assessed the association of state dram shop
      liability with various outcomes, including all-cause motor vehicle crash deaths,
      alcohol-related motor vehicle crash deaths (the most common outcome assessed in
      the studies reviewed), alcohol consumption, and other alcohol-related harms.
      There was a median reduction of 6.4% (range of values 3.7% to 11.3% reduction) in
      alcohol-related motor vehicle fatalities associated with the presence of dram
      shop liability in jurisdictions where premises are licensed. Other alcohol
      related outcomes also showed a reduction. Only two studies assessed the effects
      of enhanced enforcement initiatives on alcohol-related outcomes; findings were
      inconsistent, some indicating benefit and others none. CONCLUSIONS: According to
      Community Guide rules of evidence, the number and consistency of findings
      indicate strong evidence of the effectiveness of dram shop laws in reducing
      alcohol-related harms. It will be important to assess the possible effects of
      legal modifications to dram shop proceedings, such as the imposition of statutes
      of limitation, increased evidentiary requirements, and caps on recoverable
      amounts. According to Community Guide rules of evidence, evidence is insufficient
      to determine the effectiveness of enhanced enforcement of overservice laws for
      preventing excessive alcohol consumption and related harms.

PMID- 21855752
TI  - Dram shop liability and overservice law enforcement initiatives: A commentary.

PMID- 21855753
TI  - Enlisting bars and restaurants in the prevention of intoxication and subsequent
      harms: why it matters.

PMID- 21855754
TI  - Societal resolve and the health of children.

PMID- 21855755
TI  - Comparative-effectiveness research in cataract and refractive surgery: the CATT
      call.

PMID- 21855756
TI  - Cupid fixation for repositioning subluxated intraocular lens.
AB  - We describe the cupid fixation technique, which allows safe repositioning of a
      subluxated intraocular lens (IOL). Under subconjunctival anesthesia, the body of
      the subluxated IOL is perforated with a 10-0 polypropylene suture on a straight
      needle. The IOL is then centered and fixated at the sclera overlying the ciliary
      sulcus; the knot is tied beneath a previously created limbal intrascleral pocket.
      No intraoperative complications occurred in 24 cases in which the technique was
      performed, and successful IOL centration was achieved.

PMID- 21855757
TI  - Half-bow sliding knot: modified suture technique for scleral fixation using the
      corneoscleral pocket.
AB  - A modified suture technique for precise knot placement in the Hoffman
      corneoscleral pocket technique of scleral fixation is described. Both loops of
      the polypropylene suture passing from the intraocular device through the sclera
      and conjunctiva are retrieved from the pocket. A loop of suture is pulled through
      3 suture throws made using the second suture loop, forming a half bow. Centration
      of the intraocular lens (IOL)-capsular bag is checked. If the suture tension is
      too tight, the surgeon can easily undo the knot of the half-bow knot by pulling
      it free and can then retie the sliding knot. When the IOL-capsular bag is
      centered, the suture loop is cut and the free end removed. The second suture end
      is retrieved from the pocket, and knot tying is completed without further
      adjustment to the tension. Posterior pressure on the intraocular device centers
      it and settles the knot within the sclera at the fixation point.

PMID- 21855758
TI  - Nepafenac 0.1% versus fluorometholone 0.1% for preventing cystoid macular edema
      after cataract surgery.
AB  - PURPOSE: To compare a topical nonsteroidal antiinflammatory drug (nepafenac 0.1%)
      and a topical steroidal antiinflammatory drug (fluorometholone 0.1% ) in
      preventing cystoid macular edema (CME) and blood-aqueous barrier (BAB) disruption
      after small-incision cataract extraction with foldable intraocular lens (IOL)
      implantation. SETTING: Shohzankai Medical Foundation, Miyake Eye Hospital,
      Nagoya, Japan. DESIGN: Randomized double-masked single-center clinical trial.
      METHODS: Patients were randomized to receive nepafenac 0.1% eyedrops or
      fluorometholone 0.1% eyedrops for 5 weeks after phacoemulsification with foldable
      IOL implantation. The incidence and severity of CME were evaluated by fluorescein
      angiography, retinal foveal thickness on optical coherence tomography, and BAB
      disruption on laser flare-cell photometry. RESULTS: Thirty patients received
      nepafenac and 29 patients, fluorometholone. Five weeks postoperatively, the
      incidence of fluorescein angiographic CME was significantly lower in the
      nepafenac group (14.3%) than in the fluorometholone group (81.5%) (P<.0001). The
      fovea was thinner in the nepafenac group than in the fluorometholone group at 2
      weeks (P=.0266) and 5 weeks (P=.0055). At 1, 2, and 5 weeks, anterior chamber
      flare was significantly less in the nepafenac group than in the fluorometholone
      group (P<.0001, P<.0001, and P=.0304, respectively). The visual acuity recovery
      from baseline was significantly greater in the nepafenac group (80.0%) than in
      the fluorometholone group (55.2%) (P=.0395). There were no serious side effects
      in either group. CONCLUSION: Nepafenac was more effective than fluorometholone in
      preventing angiographic CME and BAB disruption, and results indicate nepafenac
      leads to more rapid visual recovery.

PMID- 21855759
TI  - Single perioperative subconjunctival steroid depot versus postoperative steroid
      eyedrops to prevent intraocular inflammation and macular edema after cataract
      surgery.
AB  - PURPOSE: To compare the efficacy of dexamethasone 0.1% eyedrops after
      phacoemulsification versus a single perioperative subconjunctival injection of
      betamethasone acetate 5.7 mg/mL to prevent anterior segment inflammation and
      macular edema. SETTING: Rotterdam Eye Hospital, Rotterdam, The Netherlands.
      DESIGN: Randomized clinical trial. METHODS: Patients scheduled for cataract
      surgery were randomly assigned to receive a perioperative subconjunctival
      injection of betamethasone acetate 5.7 mg/mL (Group 1) or postoperative
      administration of dexamethasone 0.1% eyedrops (Group 2). Primary outcomes were
      foveal thickness and macular edema on optical coherence tomography (OCT) and
      anterior chamber flare by a laser flare meter preoperatively and 4 weeks
      postoperatively. Secondary outcomes were intraocular pressure, need for
      additional outpatient clinic visits, phacoemulsification energy, verbal-rating
      pain scale, and corrected distance visual acuity. RESULTS: The study enrolled 400
      patients (400 eyes). Four weeks postoperatively, the mean flare values were
      significantly higher in Group 1 than in Group 2 (P=.003). The incidence of
      macular edema on OCT and clinically significant macular edema were not
      significantly different between groups (P=.685 and P=.386, respectively). No
      significant difference was observed in any other outcome measure. CONCLUSION: A
      single subconjunctival betamethasone acetate injection appears to be a useful
      alternative to prolonged postoperative administration of dexamethasone eyedrops
      in controlling intraocular inflammation and development of macular edema after
      phacoemulsification.

PMID- 21855760
TI  - Comparative analysis of the clinical outcomes with 2 multifocal intraocular lens
      models with rotational asymmetry.
AB  - PURPOSE: To compare the clinical outcomes after cataract surgery with
      implantation of 2 models of a new rotationally asymmetric multifocal IOL to
      ascertain which provides better visual performance and patient satisfaction.
      SETTING: Vissum Instituto Oftalmologico de Alicante, Alicante, Spain. DESIGN:
      Comparative case series. METHODS: Consecutive eyes of cataract patients were
      divided into 2 groups. Group A received a Lentis Mplus LS-312 MF15 IOL (with a
      near addition [add] power of +1.50 diopters [D]) and Group B, a Lentis Mplus LS
      312 MF30 IOL (with a near add power of +3.00 D). Distance, near, and intermediate
      visual acuity outcomes were evaluated preoperatively and postoperatively during a
      6-month follow-up. Postoperative contrast sensitivity, patient satisfaction,
      ocular aberrations, ocular optical quality, and defocus curves were analyzed.
      RESULTS: Patients ranged in age from 55 to 83 years. Group A comprised 22 eyes
      and Group B, 21 eyes. Both groups had a statistically significant improvement in
      uncorrected and corrected distance and corrected near visual acuities
      postoperatively (P<=.01). Group B had statistically significantly better
      uncorrected and distance-corrected near visual acuity (P<=.01) and Group A,
      significantly better uncorrected intermediate visual acuity (P=.01) at 3 months.
      There were statistically significant differences between-group differences in
      several levels of defocus based on defocus curves. There were no significant
      differences in postoperative contrast sensitivity, patient satisfaction, optical
      quality, and ocular aberrometry between groups (P>=.07). CONCLUSIONS: Both IOL
      models restored distance visual function and improved intermediate vision. Near
      visual rehabilitation was complete with the +3.00 D add IOL.

PMID- 21855761
TI  - Visual and clinical outcomes of explantation versus preservation of the
      intraocular lens during keratoprosthesis implantation.
AB  - PURPOSE: To compare the short-term visual and clinical outcomes of explantation
      versus preservation of a posterior chamber intraocular lens (PC IOL) during
      keratoprosthesis implantation. SETTING: Wilmer Eye Institute, Johns Hopkins
      University, Baltimore, Maryland, USA. DESIGN: Comparative case series. METHODS:
      This study comprised patients who had implantation of an aphakic or a
      pseudophakic Boston type I keratoprosthesis based on their lenticular status.
      Only adult patients who were pseudophakic with a PC IOL at the time of surgery
      and who had at least 1 year of follow-up were included. The postoperative
      refractive error, uncorrected and corrected visual acuities, and intraoperative
      and postoperative complications were analyzed. RESULTS: Fifteen patients with an
      unstable PC IOL had aphakic keratoprosthesis implantation with IOL explantation,
      and 10 patients had implantation of a pseudophakic keratoprosthesis. The
      postoperative best-ever visual acuity and magnitude of visual acuity improvement
      were comparable in the 2 groups. The mean postoperative spherical equivalent
      refractive error was significantly better in the aphakic group (-0.66 diopter [D]
      +/- 1.59 [SD]) than in the pseudophakic group (-3.25 +/- 3.20 D) (P=.04). The
      rate of postoperative complications in the 2 groups was low (P>.05). CONCLUSIONS:
      In this small short-term study, refractive outcomes were better in aphakic
      patients than in patients who were left pseudophakic. Although not frequent,
      posterior segment complications after IOL explantation might necessitate further
      surgeries and cause decreased visual acuity during long-term follow-up in the
      aphakic group.

PMID- 21855762
TI  - Surgical and refractive outcomes of cataract surgery with toric intraocular lens
      implantation at a resident-teaching institution.
AB  - PURPOSE: To evaluate the refractive and surgical outcomes of cataract surgery
      with toric intraocular lens (IOL) implantation performed at a teaching
      institution. SETTING: Miami Veterans Affairs Medical Center, Miami, Florida, USA.
      DESIGN: Retrospective case series. METHODS: All data were obtained by a
      retrospective chart review and entered into a standard computerized database for
      analysis. Main outcome measures included refractive and surgical outcomes after
      Acrysof toric IOL placement, including the deviation from the expected spherical
      and cylindrical correction and the incidence of ocular complications. RESULTS:
      The study comprised 94 eyes (80 patients). The mean deviation from the
      anticipated spherical correction (94 eyes) was +0.06 diopter (D) +/- 0.8 (range 
      2.6 D to +3.6 D), with 80% of eyes achieving a spherical equivalent within +/
      1.00 D of the target refraction. The postoperative refractive cylinder was
      significantly reduced from baseline, with 79% of eyes having at least a 0.50 D
      improvement in astigmatism after surgery (P<.0005). The mean deviation from the
      anticipated refractive cylinder (85 eyes) was -0.48 +/- 1.2 D (range -5.0 to +2.8
      D). The IOL was placed in an incorrect position in 2 patients, requiring a
      reoperation with IOL rotation into the proper axis. The mean follow-up was 7
      months (range 1 to 28 months). CONCLUSION: The added complexity associated with
      toric IOL placement resulted in spherical and astigmatic improvements without
      compromising patient safety beyond a level inherent in resident-based cataract
      surgery.

PMID- 21855763
TI  - Effect of scanning patterns on the results of femtosecond laser lenticule
      extraction refractive surgery.
AB  - PURPOSE: To report the clinical results of refractive lenticule extraction using
      a femtosecond laser and describe the effect of scanning patterns on the results.
      SETTING: Private laser center, Vadodara, India. DESIGN: Prospective clinical
      study. METHODS: The Visumax femtosecond laser system was used to perform
      lenticule extraction to treat refractive errors using 2 scanning trajectories.
      The laser was used to cut a refractive lenticule intrastromally to correct myopia
      or myopic astigmatism. The lenticule was then physically extracted from the
      stroma. In scanning pattern A, the laser scanned from the center out and the
      periphery in while the 2 surfaces of the lenticule were cut. In scan pattern B,
      the laser scanned from the periphery in and the center out. Outcome measures were
      corrected and uncorrected distance visual acuities and manifest refraction during
      a 6-month follow-up. Differences between the 2 scanning patterns were also
      analyzed. RESULTS: The study comprised 329 eyes of 173 patients. One week
      postoperatively, there were statistically significant differences in refractive
      outcomes (P=.03), safety (P<.01), and efficacy (P<.01), between the 2 scanning
      pattern groups. At 6 months, there were no significant differences. CONCLUSIONS:
      Early visual recovery and refractive outcomes after femtosecond lenticule
      extraction were affected by the scanning trajectory of the laser. A trajectory
      that scanned from the periphery to the center and the center to the periphery to
      cut the 2 lenticule surfaces had a positive effect on visual recovery.

PMID- 21855764
TI  - Iris-claw intraocular lenses to correct aphakia in the absence of capsule
      support.
AB  - PURPOSE: To evaluate the indications, postoperative visual efficacy, and
      complication rate after intraocular implantation of an iris-claw aphakic
      intraocular lens (IOL). SETTING: Oxford Eye Hospital, Oxford, United Kingdom.
      DESIGN: Case series. METHODS: This chart review comprised eyes with no capsule
      support that had anterior iris-fixation IOL implantation for aphakia between 2001
      and 2009. RESULTS: The study comprised 116 eyes (104 patients). Iris-claw IOLs
      were inserted during primary lens surgery in 18 eyes (15.5%), during an IOL
      exchange procedure for dislocated posterior chamber IOLs in 19 eyes (16.4%), and
      as a secondary procedure in 79 eyes (68.1%). The mean follow-up was 22.4 months
      (range 3 to 79 months). The final corrected distance visual acuity (CDVA) was
      6/12 or better in 68.9% of all eyes and in 47 of 53 eyes (88.7%) with no
      preoperative comorbidity. Complications included wound leak requiring resuturing
      in 2.6% of eyes, postoperative intraocular pressure rise in 9.5% of eyes
      (glaucoma escalation 0.8%), and cystoid macular edema in 7.7% of eyes (0.8%
      chronic). Iris-claw IOL subluxation occurred in 6.0% of eyes from 5 days to 60
      months postoperatively; all the IOLs were repositioned. Corneal decompensation
      occurred in 1.7% of eyes; 0.8% had retinal detachments. CONCLUSIONS: Iris-claw
      IOL implantation for aphakia gave a good visual outcome and can be used for a
      wide range of indications. Postoperative complication rates were comparable to,
      if not better than, those with conventional anterior chamber IOLs. Correct
      implantation technique is critical in avoiding postoperative IOL subluxation.

PMID- 21855765
TI  - Comparison of anterior segment measurements by 3 Scheimpflug tomographers and 1
      Placido corneal topographer.
AB  - PURPOSE: To compare the anterior segment measurements provided by 3 Scheimpflug
      tomographers and a Placido corneal topographer. SETTING: Private clinical
      ophthalmology practice. DESIGN: Evaluation of diagnostic test or technology.
      METHODS: In a sample of 25 consecutive patients having either refractive or
      cataract surgery, the anterior eye segment was analyzed by means of a rotating
      Scheimpflug camera (Pentacam), 2 devices with a Scheimpflug camera combined with
      a Placido disk (Sirius and TMS-5), and a Placido disk corneal topographer
      (Keratron). Measurement results were compared using analysis of variance.
      Agreement was assessed using Bland-Altman plots. RESULTS: The mean simulated
      keratometry (K) was different between the 4 instruments (P<.0001), with Keratron
      providing the highest value (44.43 diopters [D] +/- 1.28 [SD]). The Pentacam and
      Sirius provided the lowest values (44.05 +/- 1.21 D and 44.05 +/- 1.27 D,
      respectively), without statistical difference (posttest). The mean posterior
      corneal power and minimum corneal thickness were statistically different between
      the 3 Scheimpflug cameras (P<.0001 and P=.0210, respectively); 95% limits of
      agreement, however, were narrow for posterior corneal power and large for corneal
      thickness. The only 2 devices measuring the distance between the corneal
      endothelium and the anterior lens surface showed a statistically but not
      clinically significant difference (2.90 +/- 0.48 mm and 2.94 +/- 0.47 mm,
      respectively). There were no statistically significant differences in anterior
      corneal asphericity between the 4 instruments. CONCLUSION: Although the
      measurements of some parameters by different instruments were similar, caution is
      warranted before using them interchangeably.

PMID- 21855766
TI  - Differences in corneal astigmatism between partial coherence interferometry
      biometry and automated keratometry and relation to topographic pattern.
AB  - PURPOSE: To compare the corneal astigmatism values obtained with a partial
      coherence interferometry (PCI) biometer and an automated keratometer and to
      evaluate the association between these differences and corneal topographic
      patterns. SETTING: Department of Ophthalmology, Guro Hospital, Korea University
      College of Medicine, Seoul, Korea. DESIGN: Comparative case series. METHODS:
      Corneal astigmatism was measured by PCI biometry (IOLMaster) and automated
      keratometry (RK-F1 autorefractor). Eyes were divided into 3 groups based on the
      difference in absolute astigmatism values between PCI biometry and automated
      keratometry (ie, PCI biometry - automated keratometry) as follows: Group 1, more
      than 0.25 diopter (D); Group 2, within +/-0.25 D; Group 3, less than -0.25 D. The
      topographic maps were grouped into patterns of round, oval, symmetric bow tie,
      asymmetric bow tie, and irregular. Distributions of topographic patterns
      according to group and astigmatism values by topographic patterns were evaluated.
      RESULTS: The study enrolled 312 eyes. The most common pattern was the asymmetric
      bow tie (34.6%) followed by symmetric bow tie (20.5%), round (18.9%), irregular
      (16.3%), and oval (9.6%). The asymmetric bow-tie pattern was the most common in
      Group 1 and Group 2 (36.1% and 50.0%, respectively); however, in Group 3, the
      symmetric bow-tie pattern was the most common (32.8%). The distribution of
      topographic patterns by groups was statistically significantly different (P=.015,
      Pearson chi-square test). CONCLUSION: The difference in corneal astigmatism
      between the PCI biometer and automated keratometer may depend on the corneal
      topography pattern.

PMID- 21855767
TI  - Endophthalmitis after cataract surgery in China, 1995-2009.
AB  - A systematic search of the China National Knowledge Infrastructure database for
      articles on endophthalmitis after cataract surgery between 1995 and 2009
      identified 57 articles that included 403 eyes. The incidence of endophthalmitis
      after cataract surgery was 0.06% (140/233,115). Treatments included intraocular
      antibiotic injection in 54.1% of eyes and immediate vitrectomy in 40.2%. Of 356
      intraocular samples, 214 (60.1%) were culture positive; 187 (87.3%) bacterial and
      27 (12.7%) fungal. The presenting visual acuity was <5/200 in 195 (75.3%) of 259
      eyes and the final visual acuity, >=20/40 in 63 eyes (16.8%). During these 15
      years, the use of vitrectomy increased significantly (P<.05). The proportion of
      eyes with a final visual acuity of >=20/400 also increased significantly (P<.05)
      during each 5-year period. Although these represent favorable changes in the
      treatment and prognosis of endophthalmitis, there are differences between these
      outcomes and those in developed countries. A more unified therapeutic standard is
      needed to further improve the prognosis of postoperative endophthalmitis in
      China.

PMID- 21855768
TI  - Air bubble in anterior chamber as indicator of full-thickness incisions in
      femtosecond-assisted astigmatic keratotomy.
AB  - Femtosecond-assisted astigmatic keratotomy is predictable and precise but may
      occasionally lead to a full-thickness incision on the cornea and the attendant
      complications. The presence of an air bubble in the anterior chamber soon after
      creation of the keratotomy by the femtosecond laser may indicate a full-thickness
      incision. We present a case in which recognition of this clinical finding early
      in the procedure might have prevented undesirable complications, such as leakage
      of aqueous and the potential for intraocular infection.

PMID- 21855769
TI  - Descemet-stripping automated endothelial keratoplasty after bee sting of the
      cornea.
AB  - We present a case of corneal decompensation and cataract formation following a
      corneal bee sting in a patient with a history of drug abuse. Clinical findings,
      anterior segment photographs, and medical and surgical treatment are presented.
      The stinger was removed from the cornea. Systemic and topical steroids, topical
      antibiotics, and systemic and topical antiglaucoma medication and antihistamines
      were prescribed. After 3 months, combined Descemet-stripping automated
      endothelial keratoplasty (DSAEK), phacoemulsification, and intraocular lens
      implantation were performed, with significant improvement in visual acuity and
      corneal edema. To our knowledge, this is the first report of DSAEK combined with
      cataract surgery for this condition. It was found to be a safe and effective
      treatment for corneal decompensation secondary to a bee sting.

PMID- 21855770
TI  - Retinal imaging after corneal inlay implantation.
AB  - We report 2 cases of implantation with the Kamra corneal inlay to describe
      central and peripheral retinal visibility and the quality of optical coherence
      tomography (OCT) scans. Under pharmacological mydriasis, the central and
      peripheral retina was explored without disturbance by an experienced retinal
      ophthalmologist. Central color imaging was done without difficulty, and
      peripheral imaging was accurate despite a small bright shadow in every image. The
      quality of the OCT scans of the macular line, macular 3-dimensional cube, and
      macular radial protocols were 156.51, 77.49, and 84.35, respectively, in patient
      1 and 106.66, 63.03, and 64.69, respectively, in patient 2 without artifact
      scanning. The inlay allowed normal visualization of the central and peripheral
      fundus, as well as good-quality central and peripheral imaging and OCT scans.

PMID- 21855771
TI  - Simple technique for sealing clear corneal wound leaks using a dynamic anterior
      chamber air bubble.

PMID- 21855772
TI  - Perioperative antibiotic prophylaxis during cataract surgery in Greece.

PMID- 21855773
TI  - Consultation section: refractive surgical problem.

PMID- 21855780
TI  - Calculating equivalent K readings.

PMID- 21855781
TI  - Role of angle kappa in patient dissatisfaction with refractive-design multifocal
      intraocular lenses.

PMID- 21855783
TI  - Positioning patients who cannot lie flat.

PMID- 21855785
TI  - Corneal asphericity after refractive surgery.

PMID- 21855786
TI  - Acute treatment with Danshen-Gegen decoction protects the myocardium against
      ischemia/reperfusion injury via the redox-sensitive PKCE/mK(ATP) pathway in rats.
AB  - Danshen-Gegen (DG) decoction, an herbal formulation comprising Radix Salvia
      Miltiorrhiza and Radix Puerariae Lobatae, is prescribed for the treatment of
      coronary heart disease in Chinese medicine. Experimental and clinical studies
      have demonstrated that DG decoction can reduce the extent of atherosclerosis. In
      the present study, using an ex vivo rat model of myocardial ischemia/reperfusion
      (I/R) injury, we investigated the myocardial preconditioning effect of an aqueous
      DG extract prepared from an optimized weight-to-weight ratio of Danshen and
      Gegen. Short-term treatment with DG extract at a daily dose of 1 g/kg and 2 g/kg
      for 3 days protected against myocardial I/R injury in rats. The cardioprotection
      afforded by DG pretreatment was paralleled by enhancements in mitochondrial
      antioxidant status and membrane structural integrity, as well as a decrease in
      the sensitivity of mitochondria to Ca2+-stimulated permeability transition in
      vitro, particularly under I/R conditions. Short-term treatment with the DG
      extract also enhanced the translocation of PKCE from the cytosol to mitochondria
      in rat myocardium, and this translocation was inhibited by alpha-tocopherol co
      treatment with DG extract in rats. Short-term DG treatment may precondition the
      myocardium via a redox-sensitive PKCE/mK(ATP) pathway, with resultant inhibition
      of the mitochondrial permeability transition through the opening of mitochondrial
      K(ATP) channels. Our results suggest that clinical studies examining the
      effectiveness of DG extract given prophylactically in affording protection
      against myocardial I/R injury would be warranted.

PMID- 21855788
TI  - Simple rules for complex processes: new lessons from the budding yeast cell
      cycle.

PMID- 21855789
TI  - Functional expansion of the tRNA world under stress.

PMID- 21855790
TI  - Regional specialization: the NEXT big thing in nuclear RNA turnover.

PMID- 21855791
TI  - Integrated gene regulatory circuits: celebrating the 50(th) anniversary of the
      operon model.

PMID- 21855792
TI  - Commitment to a cellular transition precedes genome-wide transcriptional change.
AB  - In budding yeast, commitment to cell division corresponds to activating the
      positive feedback loop of G1 cyclins controlled by the transcription factors SBF
      and MBF. This pair of transcription factors has over 200 targets, implying that
      cell-cycle commitment coincides with genome-wide changes in transcription. Here,
      we find that genes within this regulon have a well-defined distribution of
      transcriptional activation times. Combinatorial use of SBF and MBF results in a
      logical OR function for gene expression and partially explains activation timing.
      Activation of G1 cyclin expression precedes the activation of the bulk of the
      G1/S regulon, ensuring that commitment to cell division occurs before large-scale
      changes in transcription. Furthermore, we find similar positive feedback-first
      regulation in the yeasts S. bayanus and S. cerevisiae, as well as human cells.
      The widespread use of the feedback-first motif in eukaryotic cell-cycle control,
      implemented by nonorthologous proteins, suggests its frequent deployment at
      cellular transitions.

PMID- 21855793
TI  - Distinct interactions select and maintain a specific cell fate.
AB  - The ability to specify and maintain discrete cell fates is essential for
      development. However, the dynamics underlying selection and stability of distinct
      cell types remain poorly understood. Here, we provide a quantitative single-cell
      analysis of commitment dynamics during the mating-mitosis switch in budding
      yeast. Commitment to division corresponds precisely to activating the G1 cyclin
      positive feedback loop in competition with the cyclin inhibitor Far1. Cyclin
      dependent phosphorylation and inhibition of the mating pathway scaffold Ste5 are
      required to ensure exclusive expression of the mitotic transcriptional program
      after cell cycle commitment. Failure to commit exclusively results in
      coexpression of both cell cycle and pheromone-induced genes, and a
      morphologically mixed inviable cell fate. Thus, specification and maintenance of
      a cellular state are performed by distinct interactions, which are likely a
      consequence of disparate reaction rates and may be a general feature of the
      interlinked regulatory networks responsible for selecting cell fates.

PMID- 21855794
TI  - Robust spindle alignment in Drosophila neuroblasts by ultrasensitive activation
      of pins.
AB  - Cellular signaling pathways exhibit complex response profiles with features such
      as thresholds and steep activation (i.e., ultrasensitivity). In a reconstituted
      mitotic spindle orientation pathway, activation of Drosophila Pins (LGN in
      mammals) by Galphai is ultrasensitive (apparent Hill coefficient of 3.1), such
      that Pins recruitment of the microtubule binding protein Mud (NuMA) occurs over a
      very narrow Galphai concentration range. Ultrasensitivity is required for Pins
      function in neuroblasts as a nonultrasensitive Pins mutant fails to robustly
      couple spindle position to cell polarity. Pins contains three Galphai binding
      GoLoco domains (GLs); Galphai binding to GL3 activates Pins, whereas GLs 1 and 2
      shape the response profile. Although cooperative binding is one mechanism for
      generating ultrasensitivity, we find GLs 1 and 2 act as "decoys" that compete
      against activation at GL3. Many signaling proteins contain multiple protein
      interaction domains, and the decoy mechanism may be a common method for
      generating ultrasensitivity in regulatory pathways.

PMID- 21855795
TI  - Regulatory cohesion of cell cycle and cell differentiation through interlinked
      phosphorylation and second messenger networks.
AB  - In Caulobacter crescentus, phosphorylation of key regulators is coordinated with
      the second messenger cyclic di-GMP to drive cell-cycle progression and
      differentiation. The diguanylate cyclase PleD directs pole morphogenesis, while
      the c-di-GMP effector PopA initiates degradation of the replication inhibitor
      CtrA by the AAA+ protease ClpXP to license S phase entry. Here, we establish a
      direct link between PleD and PopA reliant on the phosphodiesterase PdeA and the
      diguanylate cyclase DgcB. PdeA antagonizes DgcB activity until the G1-S
      transition, when PdeA is degraded by the ClpXP protease. The unopposed DgcB
      activity, together with PleD activation, upshifts c-di-GMP to drive PopA
      dependent CtrA degradation and S phase entry. PdeA degradation requires CpdR, a
      response regulator that delivers PdeA to the ClpXP protease in a phosphorylation
      dependent manner. Thus, CpdR serves as a crucial link between phosphorylation
      pathways and c-di-GMP metabolism to mediate protein degradation events that
      irreversibly and coordinately drive bacterial cell-cycle progression and
      development.

PMID- 21855796
TI  - The CDG1 kinase mediates brassinosteroid signal transduction from BRI1 receptor
      kinase to BSU1 phosphatase and GSK3-like kinase BIN2.
AB  - The brassinosteroid (BR) signaling pathway includes two receptor-like kinases
      (BRI1 and BAK1), a plasma membrane-associated kinase (BSK1), two phosphatases
      (BSU1 and PP2A), a GSK3-like kinase (BIN2), and two homologous transcription
      factors (BZR1 and BES1/BZR2). But the mechanisms of signal relay are not fully
      understood. Here, we show that a receptor-like cytoplasmic kinase named CDG1
      mediates signal transduction from BRI1 to BSU1. Transgenic experiments confirm
      that CDG1 and its homolog CDL1 positively regulate BR signaling and plant growth.
      Mass spectrometry analysis identified BRI1 phosphorylation sites in CDG1 and CDG1
      phosphorylation sites in BSU1. Mutations of these phosphorylation sites
      compromised the BR signaling functions. The results demonstrate that BRI1
      phosphorylates S234 to activate CDG1 kinase, and CDG1 in turn phosphorylates S764
      to activate BSU1, which inactivates BIN2 by dephosphorylating Y200 of BIN2. This
      study thus demonstrates a complete phosphorylation/dephosphorylation cascade
      linking a steroid-activated receptor kinase to a GSK3-like kinase in plants.

PMID- 21855798
TI  - Liprin-mediated large signaling complex organization revealed by the liprin
      alpha/CASK and liprin-alpha/liprin-beta complex structures.
AB  - Liprins are highly conserved scaffold proteins that regulate cell adhesion, cell
      migration, and synapse development by binding to diverse target proteins. The
      molecular basis governing liprin/target interactions is poorly understood. The
      liprin-alpha2/CASK complex structure solved here reveals that the three SAM
      domains of liprin-alpha form an integrated supramodule that binds to the CASK
      kinase-like domain. As supported by biochemical and cellular studies, the
      interaction between liprin-alpha and CASK is unique to vertebrates, implying that
      the liprin-alpha/CASK interaction is likely to regulate higher-order brain
      functions in mammals. Consistently, we demonstrate that three recently identified
      X-linked mental retardation mutants of CASK are defective in binding to liprin
      alpha. We also solved the liprin-alpha/liprin-beta SAM domain complex structure,
      which uncovers the mechanism underlying liprin heterodimerizaion. Finally,
      formation of the CASK/liprin-alpha/liprin-beta ternary complex suggests that
      liprins can mediate assembly of target proteins into large protein complexes
      capable of regulating numerous cellular activities.

PMID- 21855797
TI  - Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy.
AB  - Autophagy, the primary recycling pathway of cells, plays a critical role in
      mitochondrial quality control under normal growth conditions and in the response
      to cellular stress. The Hsp90-Cdc37 chaperone complex coordinately regulates the
      activity of select kinases to orchestrate many facets of the stress response.
      Although both maintain mitochondrial integrity, the relationship between Hsp90
      Cdc37 and autophagy has not been well characterized. Ulk1, one of the mammalian
      homologs of yeast Atg1, is a serine-threonine kinase required for mitophagy. Here
      we show that the interaction between Ulk1 and Hsp90-Cdc37 stabilizes and
      activates Ulk1, which in turn is required for the phosphorylation and release of
      Atg13 from Ulk1, and for the recruitment of Atg13 to damaged mitochondria. Hsp90
      Cdc37, Ulk1, and Atg13 phosphorylation are all required for efficient
      mitochondrial clearance. These findings establish a direct pathway that
      integrates Ulk1- and Atg13-directed mitophagy with the stress response
      coordinated by Hsp90 and Cdc37.

PMID- 21855799
TI  - Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP.
AB  - The mechanisms by which ubiquitin ligases are regulated remain poorly understood.
      Here we describe a series of molecular events that coordinately regulate CHIP, a
      neuroprotective E3 implicated in protein quality control. Through their opposing
      activities, the initiator E2, Ube2w, and the specialized deubiquitinating enzyme
      (DUB), ataxin-3, participate in initiating, regulating, and terminating the CHIP
      ubiquitination cycle. Monoubiquitination of CHIP by Ube2w stabilizes the
      interaction between CHIP and ataxin-3, which through its DUB activity limits the
      length of chains attached to CHIP substrates. Upon completion of substrate
      ubiquitination, ataxin-3 deubiquitinates CHIP, effectively terminating the
      reaction. Our results suggest that functional pairing of E3s with ataxin-3 or
      similar DUBs represents an important point of regulation in ubiquitin-dependent
      protein quality control. In addition, the results shed light on disease
      pathogenesis in SCA3, a neurodegenerative disorder caused by polyglutamine
      expansion in ataxin-3.

PMID- 21855800
TI  - Angiogenin-induced tRNA fragments inhibit translation initiation.
AB  - Angiogenin is a stress-activated ribonuclease that cleaves tRNA within anticodon
      loops to produce tRNA-derived stress-induced fragments (tiRNAs). Transfection of
      natural or synthetic tiRNAs inhibits protein synthesis and triggers the phospho
      eIF2alpha-independent assembly of stress granules (SGs), essential components of
      the stress response program. We show that selected tiRNAs inhibit protein
      synthesis by displacing eIF4G/eIF4A from uncapped > capped RNAs. tiRNAs also
      displace eIF4F, but not eIF4E:4EBP1, from isolated m(7)G cap. We identify a
      terminal oligoguanine motif that is required to displace the eIF4F complex,
      inhibit translation, and induce SG assembly. We show that the tiRNA-associated
      translational silencer YB-1 contributes to angiogenin-, tiRNA-, and oxidative
      stress-induced translational repression. Our data reveal some of the mechanisms
      by which stress-induced tRNA cleavage inhibits protein synthesis and activates a
      cytoprotective stress response program.

PMID- 21855801
TI  - Interaction profiling identifies the human nuclear exosome targeting complex.
AB  - The RNA exosome is a conserved degradation machinery, which obtains full activity
      only when associated with cofactors. The most prominent activator of the yeast
      nuclear exosome is the RNA helicase Mtr4p, acting in the context of the
      Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence of a similar
      activator(s) in humans remains elusive. By establishing an interaction network of
      the human nuclear exosome, we identify the trimeric Nuclear Exosome Targeting
      (NEXT) complex, containing hMTR4, the Zn-knuckle protein ZCCHC8, and the putative
      RNA binding protein RBM7. ZCCHC8 and RBM7 are excluded from nucleoli, and
      consistently NEXT is specifically required for the exosomal degradation of
      promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP
      subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates.
      However, at least ZCCHC7 function is restricted to nucleoli. Our results suggest
      that human nuclear exosome degradation pathways comprise modules of spatially
      organized cofactors that diverge from the yeast model.

PMID- 21855803
TI  - The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol eta
      in response to oxidative DNA damage in human cells.
AB  - Posttranslational modification of PCNA by ubiquitin plays an important role in
      coordinating the processes of DNA damage tolerance during DNA replication. The
      monoubiquitination of PCNA was shown to facilitate the switch between the
      replicative DNA polymerase with the low-fidelity polymerase eta (eta) to bypass
      UV-induced DNA lesions during replication. Here, we show that in response to
      oxidative stress, PCNA becomes transiently monoubiquitinated in an S phase- and
      USP1-independent manner. Moreover, Poleta interacts with mUb-PCNA at sites of
      oxidative DNA damage via its PCNA-binding and ubiquitin-binding motifs.
      Strikingly, while functional base excision repair is not required for this
      modification of PCNA or Poleta recruitment to chromatin, the presence of hMsh2
      hMsh6 is indispensable. Our findings highlight an alternative pathway in response
      to oxidative DNA damage that may coordinate the removal of oxidatively induced
      clustered DNA lesions and could explain the high levels of oxidized DNA lesions
      in MSH2-deficient cells.

PMID- 21855802
TI  - Identification of a rapidly formed nonnucleosomal histone-DNA intermediate that
      is converted into chromatin by ACF.
AB  - Chromatin assembly involves the combined action of histone chaperones and ATP
      dependent motor proteins. Here, we investigate the mechanism of nucleosome
      assembly with a purified chromatin assembly system containing the histone
      chaperone NAP1 and the ATP-dependent motor protein ACF. These studies revealed
      the rapid formation of a stable nonnucleosomal histone-DNA intermediate that is
      converted into canonical nucleosomes by ACF. The histone-DNA intermediate does
      not supercoil DNA like a canonical nucleosome, but has a nucleosome-like
      appearance by atomic force microscopy. This intermediate contains all four core
      histones, lacks NAP1, and is formed by the initial deposition of histones H3-H4.
      Conversion of the intermediate into histone H1-containing chromatin results in
      increased resistance to micrococcal nuclease digestion. These findings suggest
      that the histone-DNA intermediate corresponds to nascent nucleosome-like
      structures, such as those observed at DNA replication forks. Related complexes
      might be formed during other chromatin-directed processes such as transcription,
      DNA repair, and histone exchange.

PMID- 21855804
TI  - RB restricts DNA damage-initiated tumorigenesis through an LXCXE-dependent
      mechanism of transcriptional control.
AB  - The LXCXE peptide motif facilitates interaction between the RB tumor suppressor
      and a large number of cellular proteins that are expected to impinge on diverse
      biological processes. In vitro and in vivo analyses demonstrated that LXCXE
      binding function is dispensable for RB promoter association and control of basal
      gene expression. Dependence on this function of RB is unmasked after DNA damage,
      wherein LXCXE binding is essential for exerting control over E2F3 and suppressing
      cell-cycle progression in the presence of genotoxic stress. Gene expression
      profiling revealed that the transcriptional program coordinated by this specific
      aspect of RB is associated with progression of human hepatocellular carcinoma and
      poor disease outcome. Consistent with these findings, biological challenge
      revealed a requirement for LXCXE binding in suppression of genotoxin-initiated
      hepatocellular carcinoma in vivo. Together, these studies establish an essential
      role of the LXCXE binding motif for RB-mediated transcriptional control, response
      to genotoxic insult, and tumor suppression.

PMID- 21855805
TI  - p53-dependent transcription and tumor suppression are not affected in Set7/9
      deficient mice.
AB  - Methylation of specific lysine residues in the C terminus of p53 is thought to
      govern p53-dependent transcription following genotoxic and oncogenic stress. In
      particular, Set7/9 (KMT7)-mediated monomethylation of human p53 at lysine 372
      (p53K372me1) was suggested to be essential for p53 activation in human cell
      lines. This finding was confirmed in a Set7/9 knockout mouse model (Kurash et
      al., 2008). In an independent knockout mouse strain deficient in Set7/9, we have
      investigated its involvement in p53 regulation and find that cells from these
      mice are normal in their ability to induce p53-dependent transcription following
      genotoxic and oncogenic insults. Most importantly, we detect no impairment in
      canonical p53 functions in these mice, indicating that Set7/9-mediated
      methylation of p53 does not seem to represent a major regulatory event and does
      not appreciably control p53 activity in vivo.

PMID- 21855806
TI  - The methyltransferase Set7/9 (Setd7) is dispensable for the p53-mediated DNA
      damage response in vivo.
AB  - p53 is the central regulator of cell fate following genotoxic stress and oncogene
      activation. Its activity is controlled by several posttranslational
      modifications. Originally defined as a critical layer of p53 regulation in human
      cell lines, p53 lysine methylation by Set7/9 (also called Setd7) was proposed to
      fulfill a similar function in vivo in the mouse, promoting p53 acetylation,
      stabilization, and activation upon DNA damage (Kurash et al., 2008). We tested
      the physiological relevance of this circuit in an independent Set7/9 knockout
      mouse strain. Deletion of Set7/9 had no effect on p53-dependent cell-cycle arrest
      or apoptosis following sublethal or lethal DNA damage induced by radiation or
      genotoxic agents. Set7/9 was also dispensable for p53 acetylation following
      irradiation. c-myc oncogene-induced apoptosis was also independent of Set7/9, and
      analysis of p53 target genes showed that Set7/9 is not required for the p53
      dependent gene expression program. Our data indicate that Set7/9 is dispensable
      for p53 function in the mouse.

PMID- 21855807
TI  - Oral cancer therapy may influence survival of dental implants.

PMID- 21855808
TI  - Whiplash is likely to be associated with temporomandibular disorder symptoms, but
      the magnitude of this association is not known.

PMID- 21855809
TI  - Limited evidence to demonstrate that the use of hyperbaric oxygen (HBO) therapy
      reduces the incidence of osteoradionecrosis in irradiated patients requiring
      tooth extraction.

PMID- 21855810
TI  - Fluoride-containing orthodontic adhesives may reduce the occurrence of enamel
      demineralization in patients with fixed orthodontic appliances.

PMID- 21855811
TI  - There is no evidence that oral health promotion improves periodontal health in
      cardiovascular patients.

PMID- 21855812
TI  - Adjunctive antibiotics with nonsurgical periodontal therapy improve the clinical
      outcome of chronic periodontitis in current smokers.

PMID- 21855813
TI  - Analgesic Premedication may Increase the Success Rate of Local Anesthetics for
      Teeth with Irreversible Pulpitis.

PMID- 21855814
TI  - Temporomandibular disorder (TMD) pain-related disability found related to
      depression, nonspecific physical symptoms, and pain duration at 3 international
      sites.

PMID- 21855815
TI  - Rinsing with fluoride toothpaste slurry may prevent dental caries in orthodontic
      patients.

PMID- 21855816
TI  - Similar outcomes in the use of 4 different sedation techniques for pediatric
      dental surgery.

PMID- 21855817
TI  - Direct composite buildup can be a treatment option to improve tooth shape
      irregularity.

PMID- 21855818
TI  - Periodontitis and dental caries occur together.

PMID- 21855819
TI  - Diet may be Associated with the Detection of Cariogenic Bacteria in Children with
      Early Childhood Caries.

PMID- 21855820
TI  - The relationship between birth weight and growth with caries development in young
      children remains uncertain.

PMID- 21855821
TI  - Gingival recession is likely associated with tongue piercings.

PMID- 21855822
TI  - A number of variables, including age, education, smoking habits, and body mass
      index, are associated with the frequency of amalgam restorations in a Norwegian
      pregnant population.

PMID- 21855823
TI  - Effect of a nutritional intervention on childhood caries: reply to Seow.

PMID- 21855825
TI  - The ground states of iron(III) porphines: role of entropy-enthalpy compensation,
      Fermi correlation, dispersion, and zero-point energies.
AB  - Porphyrins are much studied due to their biochemical relevance and many
      applications. The density functional TPSSh has previously accurately described
      the energy of close-lying electronic states of transition metal systems such as
      porphyrins. However, a recent study questioned this conclusion based on
      calculations of five iron(III) porphines. Here, we compute the geometries of 80
      different electronic configurations and the free energies of the most stable
      configurations with the functionals TPSSh, TPSS, and B3LYP. Zero-point energies
      and entropy favor high-spin by ~4kJ/mol and 0-10kJ/mol, respectively. When these
      effects are included, and all electronic configurations are evaluated, TPSSh
      correctly predicts the spin of all the four difficult phenylporphine cases and is
      within the lower bound of uncertainty of any known theoretical method for the
      fifth, iron(III) chloroporphine. Dispersion computed with DFT-D3 favors low-spin
      by 3-53kJ/mol (TPSSh) or 4-15kJ/mol (B3LYP) due to the attractive r(-6) term and
      the shorter distances in low-spin. The very large and diverse corrections from
      TPSS and TPSSh seem less consistent with the similarity of the systems than when
      calculated from B3LYP. If the functional-specific corrections are used, B3LYP and
      TPSSh are of equal accuracy, and TPSS is much worse, whereas if the physically
      reasonable B3LYP-computed dispersion effect is used for all functionals, TPSSh is
      accurate for all systems. B3LYP is significantly more accurate when dispersion is
      added, confirming previous results.

PMID- 21855826
TI  - Exploring the roles of approach and avoidance in depression: an integrative
      model.
AB  - Human behavior can be organized around two fundamental motivational principles:
      the desire to approach positive outcomes and the desire to avoid negative
      outcomes. Both approach and avoidance motivation are relevant to a range of
      psychopathology, including depression. However, with some notable exceptions,
      avoidance processes have been underemphasized in the literature on motivational
      processes in depression. This review will examine the roles that approach and
      avoidance play in depression and will present an integrative model of approach
      and avoidance processes in depression. Both approach deficits and avoidance
      motivation are argued to play a role in limiting positive experiences and
      reinforcement for non-depressed behavior, contributing to the onset and
      maintenance of depression. In addition, avoidance processes are argued to play a
      role in negative information processing biases that may increase vulnerability to
      the onset and recurrence of depression. Lastly, avoidance processes and
      dysregulation in the connections between the approach and avoidance systems may
      contribute to depression by promoting inappropriate perseveration in the pursuit
      of unattainable approach goals. Theoretical rationales and empirical evidence for
      each of these roles are presented. Understanding the roles that both approach and
      avoidance play in depression may help to inform current conceptualizations of
      depression and improve treatment outcomes.

PMID- 21855827
TI  - A multivariate perspective on schizotypy and familial association with
      schizophrenia: a review.
AB  - Although generally accepted that schizotypal personality disorder diagnosis is
      more prevalent among relatives of individuals with schizophrenia and may be
      associated with genetic liability to schizophrenia, it seems likely that this
      diagnosis is itself heterogeneous and thus perhaps not as useful in identifying
      genes that affect schizophrenia risk (i.e. endophenotypes) as it could be. In
      contrast, symptoms and dimensions of schizotypal personality disorder may be more
      etiologically homogeneous, and thus more useful in genetic studies. The current
      review evaluated and consolidated evidence to date regarding specific symptoms
      and dimensions of schizotypal personality disorder among non-psychotic relatives
      of schizophrenia patients. Comparisons were made with relatives of affective
      disorder patients and non-psychiatric controls. Findings indicate strong support
      for elevation of social-interpersonal schizotypal symptoms among relatives of
      schizophrenia patients versus other groups along with moderate specificity.
      Results suggest only a small elevation of cognitive-perceptual and disorganized
      symptoms in relatives of schizophrenia patients and results for disorganized
      symptoms were inconsistent across studies. Thus, evidence to date supports
      further investigation of genetic associations between symptoms of schizotypal
      personality disorder and schizophrenia, and suggests that social-interpersonal
      symptoms may be particularly promising in genetic analyses of schizophrenia.

PMID- 21855829
TI  - Comparison of mortality and morbidity in patients with atrial fibrillation and
      heart failure with preserved versus decreased left ventricular ejection fraction.
AB  - Almost 50% of patients with congestive heart failure (HF) have preserved ejection
      fraction (PEF). Data on the effect of HF-PEF on atrial fibrillation outcomes are
      lacking. We assessed the prognostic significance of HF-PEF in an atrial
      fibrillation population compared to a systolic heart failure (SHF) population. A
      post hoc analysis of the National Heart, Lung, and Blood Institute-limited access
      data set of the Atrial Fibrillation Follow-up Investigation of Rhythm Management
      (AFFIRM) trial was carried out. The patients with a history of congestive HF and
      a preserved ejection fraction (EF >50%) were classified as having HF-PEF (n =
      320). The patients with congestive HF and a qualitatively depressed EF (EF <50%)
      were classified as having SHF (n = 402). Cox proportional hazards analysis was
      performed. The mean follow-up duration was 1,181 +/- 534 days/patient. The
      patients with HF-PEF had lower all-cause mortality (hazard ratio [HR] 0.62, 95%
      confidence interval [CI] 0.46 to 0.85, p = 0.003) and cardiovascular mortality
      (HR 0.56, 95% CI 0.38 to 0.84, p = 0.006), with a possible decreased arrhythmic
      end point (HR 0.39, 95% CI 0.16 to 1.006, p = 0.052) than did the patients with
      SHF. No differences were observed for ischemic stroke (HR 1.08, 95% CI 0.48 to
      2.39, p = 0.86), rehospitalization (HR 0.89, 95% CI 0.75 to 1.07, p = 0.24), or
      progression to New York Heart Association class III-IV (odds ratio 0.80, 95% CI
      0.42 to 1.54, p = 0.522). In conclusion, although patients with HF-PEF have
      better mortality outcomes than those with SHF, the morbidity appears to be
      similar.

PMID- 21855828
TI  - Anxiety sensitivity, the menstrual cycle, and panic disorder: a putative
      neuroendocrine and psychological interaction.
AB  - The 2:1 female-to-male sex difference in the prevalence of panic disorder (PD)
      suggests that there is a sex-specific vulnerability involved in the etiology
      and/or maintenance of this disorder. The purpose of this paper is to present a
      new conceptual model, which emphasizes the interaction between a cognitive
      vulnerability for PD, anxiety sensitivity, and the effects of progesterone and
      its metabolite, allopregnanolone, on behavioral and physiological responses to
      stress during the premenstrual phase. This interaction is proposed to be a
      potential sex-specific pathway that may initiate and/or maintain panic and
      anxiety symptoms in women. This review paper presents preliminary evidence from
      both the human and animal literatures to support this new model. Specific topics
      reviewed include: psychopathology related to the menstrual cycle, anxiety
      sensitivity and its relationship to the menstrual cycle, PMS, and PMDD, anxiety
      modulating effects of progesterone and its neuroactive metabolite,
      allopregnanolone, and how results from the neuroendocrine literature relate to
      psychopathology or symptoms associated with the menstrual cycle.

PMID- 21855830
TI  - Usefulness of two-dimensional and speckle tracking echocardiography in "Gray
      Zone" left ventricular hypertrophy to differentiate professional football
      player's heart from hypertrophic cardiomyopathy.
AB  - Distinguishing the pathologic hypertrophy of hypertrophic cardiomyopathy (HC)
      from the physiologic hypertrophy of professional football players (PFP) can be
      challenging when septal wall thickness falls within a "gray zone" between 12 and
      16 mm. It was hypothesized that 2-dimensional and speckle-tracking strain
      (epsilon) echocardiography could differentiate the hearts of PFPs from those of
      patients with HC with similar wall thicknesses. Sixty-six subjects, including 28
      professional American football players and 21 patients with HC, with septal wall
      thicknesses of 12 to 16 mm, along with 17 normal controls, were studied using 2
      dimensional echocardiography. Echocardiographic parameters, including modified
      relative wall thickness (RWT; septal wall thickness + posterior wall
      thickness/left ventricular end-diastolic diameter) and early diastolic annular
      tissue velocity (e'), were measured. Two-dimensional epsilon was analyzed by
      speckle tracking to measure endocardial and epicardial longitudinal epsilon and
      circumferential epsilon and radial cardiac epsilon. Septal wall thickness was
      higher in patients with HC than in PFPs (14.7 +/- 1.1 vs 12.9 +/- 0.9 mm,
      respectively, p <0.001), while posterior wall thickness showed no difference. RWT
      was larger in patients with HC than in PFPs (0.68 +/- 0.10 vs 0.48 +/- 0.06, p
      <0.001). Longitudinal endocardial epsilon and radial cardiac epsilon were
      significantly higher in PFPs than in patients with HC, while circumferential
      endocardial epsilon was no different. RWT was the parameter that most accurately
      differentiated PFPs from patients with HC. An RWT cut point of 0.6 differentiated
      PFPs from patients with HC, with an area under the curve of 0.97. In conclusion,
      a 2-dimensional echocardiographic measure of RWT (septal wall + posterior wall
      thickness/left ventricular end-diastolic dimension) accurately differentiated
      PFPs' hearts from those of patients with HC when septal wall thickness was in the
      gray zone of 12 to 16 mm. Two-dimensional strain analysis identifies variations
      in myocardial deformation between PFPs and patients with HC with gray-zone
      hypertrophy.

PMID- 21855831
TI  - Location and severity of aortic valve calcium and implications for aortic
      regurgitation after transcatheter aortic valve implantation.
AB  - Location of aortic valve calcium (AVC) can be better visualized on contrast
      enhanced multidetector row computed tomography. The present evaluation examined
      whether AVC severity and its location could influence paravalvular aortic
      regurgitation (AR) after transcatheter aortic valve implantation. A total of 79
      patients (age 80 +/- 7 years, 49% men) with preprocedural multidetector row
      computed tomography were included. Volumetric AVC quantification and its location
      were assessed. Transesophageal echocardiography was performed to assess the
      presence and site of AR after transcatheter aortic valve implantation. Receiver
      operating characteristic curves were generated to evaluate the usefulness of AVC
      in determining paravalvular AR at a specific site. Postprocedural AR of grade 1
      or more was observed in 63 patients. In most patients (n = 56, 71%), AR was of
      paravalvular origin. Calcium at the aortic wall of each valve cusp had the
      largest area under the curve (0.93, p <0.001) in predicting paravalvular AR at
      the aortic wall site compared to calcium at the valvular edge or body (area under
      the curve 0.58 and 0.67, respectively). Calcium at the valvular commissure was
      better than calcium at the valvular edge (area under the curve 0.94 vs 0.71) in
      predicting paravavular AR originating from the corresponding commissure. In
      conclusion, contrast-enhanced multidetector row computed tomography can be
      performed to quantify AVC. Both AVC severity and its exact location are important
      in determining paravalvular AR after transcatheter aortic valve implantation.

PMID- 21855832
TI  - Frequency of cardiac conduction disturbances after balloon aortic valvuloplasty.
AB  - Disturbances in atrioventricular conduction are well-recognized complications of
      transcatheter aortic valve replacement. Percutaneous balloon aortic valvuloplasty
      (BAV) is a requisite step in transcatheter aortic valve replacement; however, the
      contribution of the BAV to atrioventricular conduction disturbances has not been
      elucidated. The present analysis was undertaken to ascertain the incidence and
      type of electrocardiographic changes associated with BAV and to consider the role
      of BAV in the conduction abnormalities after transcatheter aortic valve
      replacement. In 271 consecutive patients with symptomatic, severe aortic stenosis
      undergoing BAV, a standard 12-lead electrocardiogram was obtained before and
      serially after the procedure. Each was examined by experienced
      electrocardiographers. The cohort was divided into 2 groups with regard to the
      post-BAV appearance of conduction disturbances. The clinical and procedural
      characteristics of patients with these disturbances were compared to those in
      whom no conduction disturbance appeared. After BAV, 23 patients (8.5%) met the
      study definition of "new conduction defect": 4 patients (1.5%) required permanent
      pacemaker implantation for advanced atrioventricular block. New left bundle
      branch block appeared in 9 (3.3%) and left anterior hemiblock in 7 (2.6%). New
      right bundle branch block appeared in 2 and left posterior hemiblock in 1. No
      significant difference was found in the clinical or procedural characteristics.
      The ratio of the balloon size to the left ventricular outflow tract diameter was
      1.21 +/- 1.6 in those with new conduction defects and 1.15 +/- 0.12 (p = 0.032)
      in those without. In conclusion, BAV is associated with a low incidence of
      cardiac conduction disturbances and a requirement for permanent ventricular
      pacing. The size of the valvuloplasty balloon should be carefully selected to
      avoid oversizing, which can lead to the development of postprocedure conduction
      disturbances.

PMID- 21855833
TI  - Replication of genetic association studies in aortic stenosis in adults.
AB  - Only a handful of studies have attempted to unravel the genetic architecture of
      calcific aortic valve stenosis (AS). The goal of this study was to validate genes
      previously associated with AS. Seven genes were assessed: APOB, APOE, CTGF, IL10,
      PTH, TGFB1, and VDR. Each gene was tested for a comprehensive set of single
      nucleotide polymorphisms (SNPs). SNPs were genotyped in 457 patients who
      underwent surgical aortic valve replacement, and allele frequencies were compared
      to 3,294 controls. A missense mutation in the APOB gene was significantly
      associated with AS (rs1042031, E4181K, p = 0.00001). A second SNP located 5.6
      kilobases downstream of the APOB stop codon was also associated with the disease
      (rs6725189, p = 0.000013). Six SNPs surrounding the IL10 locus were strongly
      associated with AS (0.02 > p > 6.2 * 10-11). The most compelling association for
      IL10 was found with a promoter polymorphism (rs1800872) well known to regulate
      the production of the encoded anti-inflammatory cytokine. The frequency of the
      low-producing allele was greater in cases compared to controls (30% vs 20%, p =
      6.2 * 10-11). SNPs in PTH, TGFB1, and VDR had nominal p values <0.05 but did not
      resist Bonferroni correction. In conclusion, this study suggests that subjects
      carrying specific polymorphisms in the IL10 and APOB genes are at higher risk for
      developing AS.

PMID- 21855834
TI  - Relation of physical activity to cardiovascular disease mortality and the
      influence of cardiometabolic risk factors.
AB  - Physical activity can improve several metabolic risk factors associated with
      cardiovascular disease (CVD) and is associated with a lower risk of CVD
      mortality. We sought to evaluate the extent to which metabolic risk factors
      mediate the association between physical activity and CVD mortality and whether
      physical activity provides protective effects against CVD mortality in healthy
      adults and those with metabolic risk factors. A sample of 10,261 adults from the
      Third National Health and Nutrition Examination Survey with public-access
      mortality data linkage (follow-up 13.4 +/- 3.9 years) was used. Physical activity
      was assessed by questionnaire and classified into inactive, light, and
      moderate/vigorous activity categories. Metabolic risk factors (dyslipidemia, type
      2 diabetes mellitus, obesity, hypertension, inflammation, and insulin resistance)
      were categorized using clinical thresholds. After adjusting for basic
      confounders, engaging in light or moderate/vigorous physical activity was
      associated with a lower risk of CVD mortality (p < 0.05). Adjustment for each
      risk-factor set only slightly attenuated this relation. When all risk-factor sets
      were added to the model simultaneously, light (hazard ratio 0.72, 0.62 to 0.84)
      and moderate/vigorous (hazard ratio 0.72, 0.62 to 0.85) activity remained at
      lower risk of CVD mortality. In addition, physical activity provided protective
      effects for CVD mortality in healthy subjects and those with metabolic risk
      factors in isolation or in clusters. In conclusion, physical activity was
      associated with a lower risk of CVD mortality independent of traditional and
      inflammatory risk factors. Taken together these results suggest that physical
      activity may protect against CVD mortality regardless of the presence of
      metabolic risk factors.

PMID- 21855835
TI  - Clinical and procedural characteristics of acute hemodynamic responders
      undergoing triple-site ventricular pacing for advanced heart failure.
AB  - The advantages of triple-site ventricular pacing (Tri-V) compared to conventional
      biventricular site pacing (Bi-V) have been reported. We sought to identify the
      predictors of acute hemodynamic Tri-V responders. Acute hemodynamic studies were
      performed in 32 patients with advanced heart failure during Tri-V implantation.
      After the right ventricular (RV) and left ventricular (LV) leads were implanted
      for a conventional Bi-V system, an additional pacing lead was implanted in the RV
      outflow tract for Tri-V. The LV peak +dP/dt and tau were measured during AAI, Bi
      V, and Tri-V pacing. A Tri-V responder was defined as a patient whose percentage
      of increase in the peak +dP/dt during Tri-V was >10% compared to of that during
      Bi-V. The baseline clinical variables and RV outflow tract lead location were
      analyzed to identify the characteristics of the Tri-V responders. Of the 32
      patients, 10 (31%) were classified as Tri-V responders. The LV end-diastolic
      volume was greater (246 +/- 48 vs 173 +/- 53 ml, p <0.01), and the RV outflow
      tract lead was implanted at a greater outflow tract portion (p <0.05) in the Tri
      V responders. Multivariate analysis revealed that only the baseline LV end
      diastolic volume (per 50-ml greater) predicted the Tri-V response (odds ratio
      2.87, 95% confidence interval 1.03 to 8.00, p <0.05). The area under the receiver
      operating characteristic curve for the LV end-diastolic volume was 0.84 (p <0.01)
      and an LV end-diastolic volume of >212 ml had a sensitivity of 80% and
      specificity of 77% to distinguish Tri-V responders. In conclusion, Tri-V provides
      greater hemodynamic effect for patients with a larger LV end-diastolic volume
      owing to its resynchronization effects on the LV anterior wall.

PMID- 21855836
TI  - Systematic review and meta-analysis of methotrexate use and risk of
      cardiovascular disease.
AB  - Inflammation predicts risk for cardiovascular disease (CVD) events, but the
      relation of drugs that directly target inflammation with CVD risk is not
      established. Methotrexate is a disease-modifying antirheumatic drug broadly used
      for the treatment of chronic inflammatory disorders. A systematic review and meta
      analysis of evidence of relations of methotrexate with CVD occurrence were
      performed. Cohorts, case-control studies, and randomized trials were included if
      they reported associations between methotrexate and CVD risk. Inclusions and
      exclusions were independently adjudicated, and all data were extracted in
      duplicate. Pooled effects were calculated using inverse variance-weighted meta
      analysis. Of 694 identified publications, 10 observational studies in which
      methotrexate was administered in patients with rheumatoid arthritis, psoriasis,
      or polyarthritis met the inclusion criteria. Methotrexate was associated with a
      21% lower risk for total CVD (n = 10 studies, 95% confidence interval [CI] 0.73
      to 0.87, p <0.001) and an 18% lower risk for myocardial infarction (n = 5, 95% CI
      0.71 to 0.96, p = 0.01), without evidence for statistical between-study
      heterogeneity (p = 0.30 and p = 0.33, respectively). Among prespecified sources
      of heterogeneity explored, stronger associations were observed in studies that
      adjusted for underlying disease severity (relative risk 0.64, 95% CI 0.43 to
      0.96, p <0.01) and for other concomitant medication (relative risk 0.73, 95% CI
      0.63 to 0.84, p <0.001). Publication bias was potentially evident (funnel plot,
      Begg's test, p = 0.06); excluding studies with extreme risk estimates did not,
      however, alter results (relative risk 0.81, 95% CI 0.74 to 0.89). In conclusion,
      methotrexate use is associated with a lower risk for CVD in patients with chronic
      inflammation. These findings suggest that a direct treatment of inflammation may
      reduce CVD risk.

PMID- 21855837
TI  - Effect of prolonged Bivalirudin infusion on ST-segment resolution following
      primary percutaneous coronary intervention (from the PROBI VIRI 2 study).
AB  - Bivalirudin is widely used as an anticoagulant during percutaneous coronary
      intervention (PCI) for ST-segment elevation myocardial infarction. However, an
      increase in acute stent thrombosis rates has been found in the HORIZONS-AMI
      trial. A prolonged infusion after PCI has been shown to be a safe and effective
      tool in patients undergoing urgent or elective PCI in the PROBI VIRI study. We
      examined the effects of prolonged drug infusion after primary PCI. From databases
      of 5 high-volume centers we compared a group of patients treated with a 4-hour
      prolonged infusion after PCI to 2 groups treated with a peri-PCI infusion and
      heparin plus abciximab. The primary study end point was >70% ST-segment
      resolution within 90 minutes after PCI; secondary end points were partial (>50%)
      ST-segment resolution within 90 minutes and intrahospital major and minor
      bleedings on the Acuity scale. The study population consisted of 264 patients
      undergoing primary PCI who were pretreated with aspirin and clopidogrel. The 3
      study groups did not differ significantly by baseline characteristics. The
      primary end point was achieved in 69.8%, 48.8%, and 69.6% of patients in the
      prolonged bivalirudin, bivalirudin, and heparin/abciximab groups, respectively (p
      = 0.048 for prolonged vs standard infusion, p = 0.98 for prolonged infusion vs
      abciximab). Major bleedings and other secondary study end points were not
      significantly different among study groups. In conclusion, a strategy of
      prolonged bivalirudin infusion after primary PCI seems equivalent to a strategy
      with heparin plus abciximab, with an improvement in standard infusion in
      obtaining early microvascular reperfusion.

PMID- 21855839
TI  - Effect of preinterventional ultrasound examination on frequency of procedure
      related vascular complications in percutaneous coronary interventions with
      transfemoral approach.
AB  - Vascular complications are the most frequent adverse events associated with
      percutaneous coronary interventions (PCIs) leading to an increase in morbidity
      and mortality. Puncture of the common femoral artery in its middle segment is
      proved to decrease the risk of procedure-related vascular complications. Real
      time ultrasound-guided puncture of the vessel is effective to decrease access
      site-related vascular complications but complex to perform. We evaluated whether
      an ultrasonic preinterventional examination of the femoral puncture site and skin
      marking of anatomic structures and specific vascular characteristics results in a
      decrease of access site-related vascular complications in PCIs with transfemoral
      access. Over a period of 12 months we prospectively examined all puncture sites
      before elective PCIs with transfemoral access (n = 848) using ultrasound.
      Presence, extent, and location of plaques and stenoses and exact location of
      bifurcation of the femoral artery were marked by a sonographer on the skin to
      guide the interventionists in vascular puncture. Postinterventional access site
      ultrasound was performed to determine possible access site-related complications.
      Frequency of vascular access site complications was compared to a control cohort
      (n = 1,027) that did not undergo ultrasound examination before intervention. With
      ultrasonic vascular access site management the rate of access site-related
      vascular complications was decreased from 4.2% to 1.9% (odds ratio 0.44, 0.23 to
      0.80, p = 0.005). In conclusion, preinterventional ultrasonic access site
      examination and skin marking decreases the risk of vascular complications in
      elective PCI with femoral access.

PMID- 21855838
TI  - Association of serum uric acid with incident atrial fibrillation (from the
      Atherosclerosis Risk in Communities [ARIC] study).
AB  - Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical
      practice. Current evidence suggests that serum uric acid (SUA) could be a marker
      of oxidative damage, a factor reported as a part of the mechanisms of AF. The
      purpose of the present study was to evaluate whether SUA predicted AF in the
      Atherosclerosis Risk In Communities (ARIC) study. The present analysis included
      15,382 AF-free black and white men and women, aged 45 to 64 years, from the ARIC
      study, a population-based prospective cohort in the United States. SUA was
      determined using the uricase-peroxidase method at baseline. The primary outcome
      was the incidence of AF, defined as the occurrence of AF detected using hospital
      discharge codes, scheduled study electrocardiograms, and/or death certificates
      during the follow-up period (1987 to 2004). We identified 1,085 cases of incident
      AF. In Cox proportional hazards models adjusted for age, gender, race, center,
      education, body mass index, serum glucose, systolic and diastolic blood pressure,
      low-density lipoprotein cholesterol, alcohol use, prevalent coronary heart
      disease and heart failure, serum creatinine, diuretics, and P-wave duration on
      the electrocardiogram (as a measure of left atrial size) at baseline, the hazard
      ratio of AF associated with a SD increment in SUA was 1.16 (95% confidence
      interval 1.06 to 1.26). The association of SUA with AF risk differed by race and
      gender (p for interaction <0.01). In conclusion, elevated SUA is associated with
      a greater risk of AF, particularly among blacks and women. Additional studies
      should replicate this association and explore potential mechanisms.

PMID- 21855840
TI  - Chromosomal haplotypes by genetic phasing of human families.
AB  - Assignment of alleles to haplotypes for nearly all the variants on all
      chromosomes can be performed by genetic analysis of a nuclear family with three
      or more children. Whole-genome sequence data enable deterministic phasing of
      nearly all sequenced alleles by permitting assignment of recombinations to
      precise chromosomal positions and specific meioses. We demonstrate this process
      of genetic phasing on two families each with four children. We generate
      haplotypes for all of the children and their parents; these haplotypes span all
      genotyped positions, including rare variants. Misassignments of phase between
      variants (switch errors) are nearly absent. Our algorithm can also produce
      multimegabase haplotypes for nuclear families with just two children and can
      handle families with missing individuals. We implement our algorithm in a suite
      of software scripts (Haploscribe). Haplotypes and family genome sequences will
      become increasingly important for personalized medicine and for fundamental
      biology.

PMID- 21855842
TI  - Risk factors for eclampsia: a population-based study in Washington State, 1987
      2007.
AB  - OBJECTIVE: We sought to investigate whether previously identified risk factors
      are associated with eclampsia in a contemporary, heterogeneous cohort of women.
      STUDY DESIGN: Data were collected from birth certificate and hospital discharge
      records and used to conduct a population-based case-control study among women
      giving birth to singletons in Washington State from 1987 through 2007. We used
      multivariable logistic regression to estimate odds ratios and 95% confidence
      intervals. Multiple imputation procedures were used to address missing data.
      RESULTS: Risk of eclampsia was greater in nulliparous compared to parous women.
      Being a young mother (< 20 years) or an older mother (>= 35 years) were each
      associated with elevated eclampsia risk. Longer birth interval, low socioeconomic
      status, gestational diabetes, prepregnancy obesity, and weight gain during
      pregnancy above or below recommended guidelines were positively associated with
      eclampsia. Multiparity and smoking were inversely associated with eclampsia risk.
      CONCLUSION: Exposures identified more than a decade ago continue to be associated
      with eclampsia in contemporary birth cohorts.

PMID- 21855841
TI  - Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause
      a recessive hypomyelinating leukodystrophy.
AB  - Leukodystrophies are a heterogeneous group of inherited neurodegenerative
      disorders characterized by abnormal white matter visible by brain imaging. It is
      estimated that at least 30% to 40% of individuals remain without a precise
      diagnosis despite extensive investigations. We mapped tremor-ataxia with central
      hypomyelination (TACH) to 10q22.3-23.1 in French-Canadian families and sequenced
      candidate genes within this interval. Two missense and one insertion mutations in
      five individuals with TACH were uncovered in POLR3A, which codes for the largest
      subunit of RNA polymerase III (Pol III). Because these families were mapped to
      the same locus as leukodystrophy with oligodontia (LO) and presented clinical and
      radiological overlap with individuals with hypomyelination, hypodontia and
      hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine
      individuals with 4H and eight with LO. In total, 14 recessive mutations were
      found in 19 individuals with TACH, 4H, or LO, establishing that these
      leukodystrophies are allelic. No individual was found to carry two nonsense
      mutations. Immunoblots on 4H fibroblasts and on the autopsied brain of an
      individual diagnosed with 4H documented a significant decrease in POLR3A levels,
      and there was a more significant decrease in the cerebral white matter compared
      to that in the cortex. Pol III has a wide set of target RNA transcripts,
      including all nuclear-coded tRNA. We hypothesize that the decrease in POLR3A
      leads to dysregulation of the expression of certain Pol III targets and thereby
      perturbs cytoplasmic protein synthesis. This type of broad alteration in protein
      synthesis is predicted to occur in other leukoencephalopathies such as
      hypomyelinating leukodystrophy-3, caused by mutations in aminoacyl-tRNA
      synthetase complex-interacting multifunctional protein 1 (AIMP1).

PMID- 21855843
TI  - Evolution of surgical management of early-stage endometrial cancer.
AB  - OBJECTIVE: We sought to examine the evolution of surgical care for early-stage
      endometrial cancers and factors affecting use of laparoscopy. STUDY DESIGN: Women
      with surgically managed early-stage endometrial cancer were divided into 2 groups
      corresponding to before and after addition of faculty with formal fellowship
      training in laparoscopic staging and access to a robotic surgery platform.
      RESULTS: In all, 502 women were identified. Laparoscopic management increased
      from 24-69% between time periods (P < .0001). Performance of comprehensive
      surgical staging, and lymph node counts, increased (P < .0001) despite an
      increase in median body mass index (P = .001). A traditional "straight stick"
      technique was performed in 72% of laparoscopic cases during the later period.
      Laparoscopy patients had lower estimated blood losses and shorter hospital stays
      (each P < .0001) compared to laparotomy patients. CONCLUSION: Addition of faculty
      with formal fellowship training in laparoscopic staging and access to a robotic
      surgery platform shifted management of early-stage endometrial cancer toward
      laparoscopy.

PMID- 21855845
TI  - Major dietary patterns and blood pressure patterns during pregnancy: the
      Generation R Study.
AB  - OBJECTIVE: We sought to evaluate associations between dietary patterns and
      systolic blood pressure (SBP) and diastolic blood pressure during pregnancy.
      STUDY DESIGN: This was a prospective study of 3187 pregnant women. Participants
      completed a food-frequency questionnaire in early pregnancy. The Mediterranean
      dietary pattern, comprising high intake of vegetables, vegetable oils, pasta,
      fish, and legumes, and the Traditional dietary pattern, comprising high intake of
      meat and potatoes, were identified using factor analysis. RESULTS: A higher SBP
      was observed among mothers with high Traditional pattern adherence. Low adherence
      to the Mediterranean pattern was also associated with higher SBP but only in
      early and mid pregnancy. A higher diastolic blood pressure throughout pregnancy
      was observed in mothers with high adherence to the Traditional pattern and low
      adherence to the Mediterranean pattern. These effect estimates were most
      pronounced in mid pregnancy. CONCLUSION: Low adherence to a Mediterranean and
      high adherence to a Traditional dietary pattern is associated with a higher blood
      pressure in pregnancy.

PMID- 21855846
TI  - Microinvasive squamous carcinoma (FIGO stage IA1) of the cervix: are there
      colposcopic criteria for the diagnosis?
AB  - OBJECTIVE: The purpose of this study was to evaluate colposcopic sensitivity in
      the diagnosis of microinvasive squamous carcinoma of the cervix. STUDY DESIGN: We
      conducted a cross-sectional study in 151 patients from 1991-2008. The colposcopic
      findings of microinvasion suspicion were described by the International
      Federation for Cervical Pathology and Colposcopy in 2003. RESULTS: There has been
      colposcopic suspicion of invasion in 35 patients, which represents a sensitivity
      of 23%. The major colposcopic findings that were observed in the transformation
      zone included acetowhite epithelium in 21% (32/151 patients), coarse punctuation
      in 19% (29/151 patients), coarse mosaic in 17% (26/151 patients), and atypical
      vessels in 3.9% (6/151 patients). Suspicion of microinvasion was found in 14.5%
      of unsatisfactory colposcopy and in 8.6% of satisfactory colposcopy. CONCLUSION:
      The sensitivity of colposcopy in the diagnosis of microinvasive carcinoma of the
      cervix was low. Colposcopy plays an important role in directing the biopsy to the
      most suspicious area. The definitive diagnosis of microinvasive squamous
      carcinoma is established only by histologic study.

PMID- 21855847
TI  - Knockdown of MADD and c-FLIP overcomes resistance to TRAIL-induced apoptosis in
      ovarian cancer cells.
AB  - OBJECTIVE: The clinical utility of tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) in the treatment of established human malignancies is
      limited by the development of resistance to TRAIL. We hypothesized that knockdown
      of map-kinase activating death domain containing protein (MADD), a TRAIL
      resistance factor, may overcome TRAIL resistance in ovarian cancer cells. STUDY
      DESIGN: MADD expression in resected ovarian cancer specimens and cell lines was
      quantified with the use of polymerase chain reaction. Sensitivity of ovarian
      cancer cell lines to TRAIL, with or without MADD knockdown, was assessed.
      RESULTS: MADD is expressed at relatively higher levels in human malignant ovarian
      cancer tissues and cell lines, compared with normal ovarian tissues. The cell
      lines OVCA429 and OVCAR3 were susceptible, and cell lines CAOV-3 and SKOV-3 were
      resistant to TRAIL. MADD knockdown in CAOV-3 cells, but not in SKOV-3 cells,
      conferred TRAIL sensitivity. Knockdown of cellular Fas-associated death domain
      like interleukin-1 beta-converting enzyme-inhibitory protein (c-FLIP) in SKOV-3
      cells increased spontaneous and TRAIL-induced apoptosis, which was further
      increased on MADD knockdown. CONCLUSION: MADD/c-FLIP(L) knockdown can render
      TRAIL-resistant ovarian cancer cells susceptible to TRAIL.

PMID- 21855848
TI  - High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?
AB  - OBJECTIVE: Clinical observations suggest a role for the fetus in the maternal
      manifestations of preeclampsia, but the possible signaling mechanisms remain
      unclear. This study compares the fetal plasma concentrations of adenosine from
      normal pregnancies with those from preeclampsia. STUDY DESIGN: This secondary
      data analysis included normal pregnancies (n = 27) and patients with preeclampsia
      (n = 39). Patients with preeclampsia were subclassified into patients with (n =
      25) and without (n = 14) abnormal uterine artery Doppler velocimetry (UADV).
      RESULTS: Fetal plasma concentrations of adenosine were significantly higher in
      patients with preeclampsia (1.35 +/- 0.09 MUmol/L) than in normal pregnancies
      (0.52 +/- 0.06 MUmol/L; P < .0001). Fetal plasma concentrations of adenosine in
      patients with preeclampsia with abnormal UADV (1.78 +/- 0.15 MUmol/L), but not
      with normal UADV (0.58 +/- 0.14 MUmol/L), were significantly higher than in
      normal pregnancies (P < .0001). CONCLUSION: Patients with preeclampsia with
      sonographic evidence of chronic uteroplacental ischemia have high fetal plasma
      concentrations of adenosine.

PMID- 21855849
TI  - Mortality in acute type A aortic dissection: validation of the Penn
      classification.
AB  - BACKGROUND: Intraoperative and in-hospital mortality after surgery for acute type
      A dissection depends largely on preoperative conditions, specifically the
      presence of localized or generalized ischemia. Recently, the Penn classification
      of patients with acute type A aortic dissection has been described. The primary
      aim was to validate the Penn classification and to investigate preoperative
      variables related to mortality. METHODS: All consecutive patients operated for
      acute type A aortic dissection, 1990 to 2009 (n = 360), were included in a
      retrospective observational study. Univariate and multivariable analyses were
      used to identify variables related to intraoperative and in-hospital mortality.
      Propensity scoring was used to adjust for treatment selection bias. RESULTS:
      Overall intraoperative mortality was 7% (24 of 360) and in-hospital mortality was
      19% (69 of 360). Two hundred nineteen patients (61%) were Penn class Aa (14% in
      hospital mortality), 51 (14%) class Ab (24% mortality), 63 (18%) class Ac (24%
      mortality), and 27 (8%) class Abc (44% mortality), p =0.007. In multivariable
      analysis, Penn class Ac and Abc were independently related to intraoperative
      death (odds ratio 5.0 and 5.4, respectively), and Penn class Abc and non-Aa were
      independently related to in-hospital mortality (odds ratio 3.4 and 2.3,
      respectively). Concomitant coronary artery bypass grafting, older age, DeBakey
      type I dissection, and prolonged periods of cardiopulmonary bypass and
      hypothermic circulatory arrest were also independently associated with mortality.
      CONCLUSIONS: The Penn classification of acute type A aortic dissection is
      purposeful and its continued usage encouraged. Penn class indicating localized or
      generalized ischemia is independently related to intraoperative and in-hospital
      mortality.

PMID- 21855850
TI  - Induced interleukin-19 contributes to cell-mediated immunosuppression in patients
      undergoing coronary artery bypass grafting with cardiopulmonary bypass.
AB  - BACKGROUND: Coronary artery bypass graft (CABG) surgery with cardiopulmonary
      bypass (CPB) promotes immunosuppression, which predisposes patients to infectious
      complications. We investigated the role of interleukin (IL)-19 in the functions
      of CD4+ T cells in patients undergoing CABG with CPB. METHODS: Blood samples were
      withdrawn from 42 patients undergoing elective CABG with CPB. Serum levels of IL
      19 were analyzed by enzyme-linked immunosorbent assay (ELISA). The CD4+/CD25+ T
      cell population was determined with flow cytometry. Isolated CD4+ T cells were
      cultured and assayed for proliferation and cytokine production under phorbol
      myristate acetate/ionomycin stimulation. Cytokine production and Foxp3 mRNA
      expression in CD4+ T cells from healthy volunteers with or without IL-19
      treatment were determined with ELISA and real-time polymerase chain reaction,
      respectively. RESULTS: Proliferation percentages were 162%, 48%, 34%, and 39%,
      and interferon (IFN)-gamma production was 1.22 ng/mL, 0.56 ng/mL, 0.33 ng/mL, and
      0.35 ng/mL in the CD4+ T cells of patients before CPB and at 24 hours, 48 hours,
      and 96 hours, respectively, after CPB. Serum levels of IL-19 were higher but
      negatively correlated with CD4+ T-cell proliferation and IFN-gamma production.
      The populations of CD4+/CD25+ T cells and expression of Foxp3 mRNA in T cells
      were higher and were positively correlated with IL-19 levels after CPB. Treatment
      with IL-19 reduced T-cell proliferation and IFN-gamma production, increased Foxp3
      mRNA expression, and induced the regulatory activity of CD4+ T cells.
      CONCLUSIONS: Interleukin-19 reduces T-cell responses and promotes the regulatory
      activity of CD4+ T cells. Induced IL-19 in patients undergoing CABG with CPB
      contributes to cell-mediated immunosuppression.

PMID- 21855851
TI  - Risk factors and survival in patients with respiratory failure after cardiac
      operations.
AB  - BACKGROUND: Respiratory failure is a known complication of cardiac operations and
      contributes to postoperative morbidity and death. This study assessed the
      relevance of risk factors in the development of respiratory failure, defined as
      postoperative ventilation exceeding 48 hours, and looked at the effect of
      respiratory failure on short-term and long-term mortality rates. METHODS: De
      identified data for patients who underwent cardiac surgical procedures at The
      Prince Charles Hospital between January 2002 and December 2007 were collected
      prospectively and analyzed using logistic regression to identify significant risk
      factors associated with respiratory failure. Long-term mortality data were
      analyzed for patients who underwent operations between 1994 and 2005 using Kaplan
      Meier survival curves. RESULTS: The risk factor analysis included 7,440 patients.
      Identified risk factors for respiratory failure included critical preoperative
      state, neurologic dysfunction, poor left ventricular function, active
      endocarditis, chronic obstructive pulmonary disease, elevated preoperative
      creatinine, previous cardiac operation, and age. Survival was assessed in 18,488
      patients and demonstrated increased short-term and long-term mortality rates when
      respiratory failure developed and increased mortality rates with increasing
      duration of respiratory failure. CONCLUSIONS: Respiratory failure is complication
      of cardiac operations associated with increased mortality and cost.
      Identification of patients at risk of respiratory failure may help select
      surgical candidates and aid resource planning and optimization.

PMID- 21855852
TI  - Elevation of antidonor immunoglobulin M levels precedes acute lung transplant
      rejection.
AB  - BACKGROUND: No useful noninvasive biomarker exists for diagnosing acute rejection
      after lung transplantation (LTx). In this study, antidonor T-cell antibodies were
      monitored daily in living-donor lobar LTx recipients to determine whether they
      are correlated with the onset of steroid-responsive typical acute rejection.
      METHODS: Ten nonsensitized patients who underwent bilateral living-donor lobar
      LTxs donated from 2 persons were analyzed. In 5 patients, unilateral acute
      rejection developed during the first 14 days after LTx and responded to
      subsequent pulse steroid therapies. The other patients experienced no rejection
      episodes during the period. Immunoreactivity against T cells from each lobe of
      the donors was monitored daily by detecting antidonor immunoglobulin (Ig) M and
      IgG using flow cytometry crossmatching for 14 days after LTx. RESULTS: There was
      a remarkable increase in IgM levels against rejected grafts around the onset of
      acute rejection, but this increase was not observed against nonrejected grafts.
      The mean IgM levels against rejected grafts 14 days after transplantation was
      significantly higher than that against nonrejected grafts in the acute rejection
      group (p = 0.009) and the no rejection group (p = 0.010). In the acute rejection
      group, the IgM level against rejected grafts became significantly higher than
      those against nonrejected grafts 2 days before the clinical onset of acute
      rejection. These trends were statistically marginal or not detected for IgG
      levels. CONCLUSIONS: Significant immunoreactivity of IgM, but not IgG, preceded
      the clinical onset of acute rejection. Antidonor IgM monitoring can contribute to
      the early detection of steroid-responsive acute rejection.

PMID- 21855853
TI  - Regional variation in patient risk factors and mortality after coronary artery
      bypass grafting.
AB  - BACKGROUND: Geographic variations in patient risk factors and operative mortality
      after coronary artery bypass graft surgery have not been well studied. METHODS:
      Using The Society of Thoracic Surgeons National Cardiac Database, a retrospective
      cohort study was performed of patients undergoing isolated coronary artery bypass
      graft surgery from 2004 to 2007 (n = 504,608). Records were sorted into four
      major geographic regions (Northeast, Midwest, South, and West) and compared with
      respect to patient risk profiles and outcomes. Using marginal and hierarchical
      logistic regression, risk-adjusted operative mortality rates were compared across
      regions and variation assessed within regions, states and hospital referral
      regions. RESULTS: Patient risk profiles in the Northeast and West appeared
      similar, as did profiles in the Midwest and South. Risk-adjusted mortality rates
      were as follows: Northeast 1.63%, Midwest 2.01%, South 2.25%, and West 1.82%.
      Compared with the Northeast, mortality rates in the Midwest and South were
      higher, with the following odds ratios (95% confidence intervals): Midwest 1.26
      (1.12 to 1.42), South 1.44 (1.27 to 1.62), and West 1.12 (0.98 to 1.28). Major
      geographic regions accounted for 16.5% of the variation observed in mortality
      rates; states and hospital referral regions accounted for 17.8% and 65.7%,
      respectively. CONCLUSIONS: Variations in absolute coronary artery bypass graft
      surgery mortality rates across large regions were subtle, although rates within
      the Northeast were comparatively lower. Most of the variation was seen at the
      hospital referral region level. Given that geographic location has not been
      routinely incorporated into statistical risk model predictions, additional
      research appears warranted to identify regional "best care" practices and to
      advance nationwide improvements in cardiac surgical patient outcomes.

PMID- 21855854
TI  - Transplantation of high panel-reactive antibody left ventricular assist device
      patients without crossmatch using on-bypass pheresis and alemtuzumab.
AB  - BACKGROUND: Highly sensitized (HS) left ventricular assist device (LVAD) patients
      with high panel-reactive antibody (PRA) levels present a challenge. Alemtuzumab,
      a potent depleting agent for T and B lymphocytes (months to years), and
      plasmapheresis, offer an opportunity for heart transplantation to these patients
      who might die of VAD complications on the transplant waiting list. This study
      compared rates of acute rejection and survival of a HS LVAD cohort with a
      contemporaneous control group after heart transplant. METHODS: Clinical courses
      of 31 consecutive patients who underwent transplantation between January 2006 and
      January 2011 were reviewed. Eight patients with a T or B PRA of 70 or more (HS+)
      received non-crossmatched, ABO-compatible hearts using intraoperative
      plasmapheresis and alemtuzumab induction. Controls (HS-) received basiliximab
      induction. Acute rejection was defined as International Society for Heart and
      Lung Transplantation grades 2R or higher, or antibody-mediated rejection.
      RESULTS: The difference in survival between HS+ and HS- groups at 1 year (100% vs
      94%) or at a mean follow-up of 2.3 and 2.4 years (75% vs 70%) was not
      significant. Retrospective lymphocytotoxic crossmatches were positive in 7 of 8
      HS+ patients (6 T+ and B+, 1 B+) vs none in the HS- group (p < 0.001). There was
      a trend toward increased risk of cellular rejection per 100 patient-days beyond 1
      year in the HS+ group (p = 0.07). Risk of humoral rejection was significantly
      increased in the HS+ group (38% vs 4%; p = 0.04). CONCLUSIONS: Heart
      transplantation with plasmapheresis and alemtuzumab in HS LVAD patients, most
      with a positive crossmatch, does not compromise midterm survival. The expected
      higher rates of rejection, especially beyond the first postoperative year, demand
      adjustments in surveillance strategies and immunosuppressive management.

PMID- 21855855
TI  - Do occlusal contact areas of maximum closing position during gum chewing and
      intercuspal position coincide?
AB  - OBJECTIVE: Occlusal contact area (OCA) is most important during the occlusal
      phase when food particles are being pulverized. OCA is most easily measured
      statically at the maximum intercuspal position (ICP). However, the assumption of
      coincidence between dynamic maximum closing position (MCP) and statically
      determined ICP has not been previously tested. The purpose of this study is to
      introduce a method of quantifying OCA of all teeth during dynamic mastication to
      determine whether the OCA at the dynamic MCP during chewing is similar to the
      statically determined maximum possible OCA. DESIGN: Thirteen healthy females
      participated in this study. Morphologic tooth shape data were measured from
      dental models using an automatic 3D digitizer. Mandibular movement during gum
      chewing was recorded using an optoelectronic analysis system with 6 degrees of
      freedom, and ten cycles were selected for analysis. The dynamic OCA was estimated
      with a measurement system combining 3D tracking of mandibular movements with 3D
      digitization of tooth shape. RESULTS: The estimated mean 3D difference between
      the incisor position at ICP and MCP was 0.129 mm. At the dynamic MCP, the maximum
      OCA was 98.5% (68.42 mm(2)) of the maximum possible contact area in the static
      ICP (69.46 mm(2)). Both between-subject and within-subject variation were least
      at the dynamic MCP. CONCLUSION: The maximum OCA during chewing is nearly
      identical to statically determined maximum possible OCA.

PMID- 21855856
TI  - Dentine as a bioactive extracellular matrix.
AB  - As a mineralised connective tissue, dentine is well adapted to its functional
      role as a major structural component of the tooth. Although similar in
      composition to bone, dentine matrix is not remodelled physiologically and
      traditionally, has been regarded as a rather inert tissue. Nevertheless, dentine
      pulp demonstrates strong regenerative potential which allows it to respond to
      disease and traumatic injury. Such responses are strongly influenced by cell
      matrix interactions and modified by disease processes, including infection and
      inflammation. The identification of many bioactive molecules bound within dentine
      matrix has allowed their potential involvement in regenerative and other tissue
      responses to be better understood and new opportunities to be recognised for
      novel clinical therapies.

PMID- 21855857
TI  - Serotonin 2A receptors in obsessive-compulsive disorder: a positron emission
      tomography study with [11C]MDL 100907.
AB  - BACKGROUND: Serotonergic abnormalities are hypothesized to contribute to
      obsessive-compulsive disorder (OCD). This study used positron emission tomography
      with the radioligand [11C]MDL 100907 to examine whether the distribution of
      serotonin 2A (5-HT(2A)) receptors is altered in OCD. METHODS: Nineteen OCD
      subjects, free of psychiatric medications and depression, and 19 matched healthy
      subjects underwent positron emission tomography scans following injection of
      [11C]MDL 100907. Total distribution volumes were derived by kinetic analysis
      using the arterial input function. Two measures of 5-HT(2A) availability were
      computed: the ratio at equilibrium of specifically bound radiotracer either to
      nondisplaceable radiotracer in tissue (BP(ND)) or to unmetabolized tracer in
      arterial plasma (BP(p)). Groups were compared using a region of interest (ROI)
      analysis and voxelwise analysis of spatially normalized parametric maps. ROIs
      included cortical (orbitofrontal, dorsolateral prefrontal, medial prefrontal,
      anterior cingulate, temporal, parietal, occipital, and insular cortex) and limbic
      (entorhinal cortex, parahippocampal gyrus, and medial temporal lobe) regions.
      RESULTS: No significant group differences were observed in [11C]MDL 100907 BP(ND)
      or BP(p) in the ROIs or in the voxelwise analysis of BP(ND) maps. There was a
      significant correlation in the orbitofrontal cortex between [11C]MDL 100907
      binding and age of onset, with earlier age of onset associated with higher
      binding. CONCLUSIONS: Adults with OCD are not characterized as a group by major
      changes in 5-HT(2A) availability in cortical or limbic brain regions. Further
      research is warranted to examine potential differences in 5-HT(2A) availability
      between early- and late-onset OCD and to assess 5-HT(2A) function in relation to
      other neurotransmitter systems implicated in OCD.

PMID- 21855858
TI  - Gene profiling reveals a role for stress hormones in the molecular and behavioral
      response to food restriction.
AB  - BACKGROUND: Food restriction is known to enhance learning and motivation. The
      neural mechanisms underlying these responses likely involve alterations in gene
      expression in brain regions mediating the motivation to feed. METHODS: Analysis
      of gene expression profiles in male C57BL/6J mice using whole-genome microarrays
      was completed in the medial prefrontal cortex, nucleus accumbens, ventral
      tegmental area, and the hypothalamus following a 5-day food restriction.
      Quantitative polymerase chain reaction was used to validate these findings and
      determine the time course of expression changes. Plasma levels of the stress
      hormone corticosterone (CORT) were measured by enzyme-linked immunosorbent assay.
      Expression changes were measured in adrenalectomized animals that underwent food
      restriction, as well as in animals receiving daily injections of CORT.
      Progressive ratio responding for food, a measure of motivated behavior, was
      assessed after CORT treatment in restricted and fed animals. RESULTS: Brief food
      restriction results in an upregulation of peripheral stress responsive genes in
      the mammalian brain. Time-course analysis demonstrated rapid and persistent
      expression changes in all four brain regions under study. Administration of CORT
      to nonrestricted animals was sufficient to induce a subset of the genes, and
      alterations in gene expression after food restriction were dependent on intact
      adrenal glands. CORT can increase the motivation to work for food only in the
      restricted state. CONCLUSIONS: These data demonstrate a central role for CORT in
      mediating both molecular and behavioral responses to food restriction. The stress
      hormone-induced alterations in gene expression described here may be relevant for
      both adaptive and pathological responses to stress.

PMID- 21855859
TI  - Reduced amygdala serotonin transporter binding in posttraumatic stress disorder.
AB  - BACKGROUND: The amygdala is a key site where alterations in the regulation of the
      serotonin transporter (5-HTT) may alter stress response. Deficient 5-HTT function
      and abnormal amygdala activity have been hypothesized to contribute to the
      pathophysiology of posttraumatic stress disorder (PTSD), but no study has
      evaluated the 5-HTT in humans with PTSD. On the basis of translational models, we
      hypothesized that patients diagnosed with PTSD would exhibit reduced amygdala 5
      HTT expression as measured with positron emission tomography and the recently
      developed 5-HTT-selective radiotracer [(11)C]AFM. METHODS: Fifteen participants
      with PTSD and 15 healthy control (HC) subjects without trauma history underwent a
      resting-state positron emission tomography scan. RESULTS: [(11)C]AFM binding
      potential (BP(ND)) within the combined bilateral amygdala region of interest was
      significantly reduced in the PTSD group compared with the HC group (p = .027;
      16.3% reduction), which was largely driven by the between-group difference in the
      left amygdala (p = .008; 20.5% reduction). Furthermore, amygdala [(11)C]AFM
      BP(ND) was inversely correlated with both Hamilton Rating Scale for Anxiety
      scores (r = -.55, p = .035) and Montgomery-Asberg Depression Rating Scale scores
      (r = -.56, p = .029). CONCLUSIONS: Our findings of abnormally reduced amygdala 5
      HTT binding in PTSD and its association with higher anxiety and depression
      symptoms in PTSD patients support a translational neurobiological model of PTSD
      directly implicating dysregulated 5-HTT signaling within neural systems
      underlying threat detection and fear learning.

PMID- 21855860
TI  - Dendritic cells transfected with PD-L1 recombinant adenovirus induces T cell
      suppression and long-term acceptance of allograft transplantation.
AB  - The purpose of this study is to assess the potential of dendritic cells
      transfected with PD-L1 recombinant adenovirus induces CD8+ T cell suppression and
      kidney allograft tolerance. To prove it, DCs transfected with PD-L1 recombinant
      adenovirus (DC/Ad-PD-L1) were transferred into the MHC-mismatched rat kidney
      transplants. After kidney transplantation, the mixed lymphocyte reaction (MLR)
      assay and kidney function were analyzed. The results demonstrated that after
      administration of DC/Ad-PD-L1, the proliferation, cytokines secretion and
      activation marker expression of CD8+ T cells were suppressed. In addition, DC/Ad
      PD-L1 could improve kidney function and survival of transplants. The findings
      suggested that DC/Ad-PD-L1 could induce CD8+ T cell tolerance and lead to kidney
      allograft tolerance, which provided a promising finding for clinical application.

PMID- 21855861
TI  - Superior vena cava syndrome arising from a solitary metastasis to an indwelling
      catheter.

PMID- 21855862
TI  - Detection of type II endoleaks in abdominal aortic aneurysms after endovascular
      repair.
AB  - Abdominal aortic aneurysm (AAA) is a condition where the weakening of the aortic
      wall leads to its widening and the generation of a thrombus. To prevent a
      possible rupture of the aortic wall, AAA can be treated non-invasively by means
      of the endovascular aneurysm repair technique (EVAR), consisting of placing a
      stent-graft inside the aorta by a cateter to exclude the aneurysm sac from the
      blood circulation. A major complication is the presence of liquid blood
      turbulences, called endoleaks, in the thrombus formed in the space between the
      aortic wall and the stent-graft. In this paper we propose an automatic method for
      the detection of type II endoleaks in computer tomography angiography (CTA)
      images. The lumen and thrombus in the aneurysm area are first segmented using a
      radial model approach. Then, these regions are split into Thrombus Connected
      Components (TCCs) using a watershed-based segmentation and geometric and image
      content-based characteristics are obtained for each TCC. Finally, TCCs are
      classified into endoleaks and non-endoleaks using a multilayer Perceptron (MLP)
      trained on manual labeled sample TCCs provided by experts.

PMID- 21855863
TI  - Measurement of phase synchrony of coupled segmentation clocks.
AB  - The temporal behavior of segmentation clock oscillations shows phase synchrony
      via mean field like coupling of delta protein restricting to nearest neighbors
      only, in a configuration of cells arranged in a regular three dimensional array.
      We found the increase of amplitudes of oscillating dynamical variables of the
      cells as the activation rate of delta-notch signaling is increased, however, the
      frequencies of oscillations are decreased correspondingly. Our results show the
      phase transition from desynchronized to synchronized behavior by identifying
      three regimes, namely, desynchronized, transition and synchronized regimes
      supported by various qualitative and quantitative measurements.

PMID- 21855864
TI  - Dynamically generated models for medical decision support systems.
AB  - Doctors applying mechanical ventilation need to find the best balance between
      benefit and risk for the patient. Mathematical models simulating patient's
      reactions to alterations in the ventilation regime may be employed. A framework
      is introduced that is able to dynamically combine mathematical models from
      different model families to form a complex interacting model system. Each of
      these families consists of submodels differing in complexity of dynamics
      formulation or anatomical/geometrical resolution. The interaction of model
      systems reveals qualitatively varying results depending on the complexity of the
      involved models. Realistic overlaying of respiratory and cardiovascular rhythms
      can be detected in blood gas concentrations.

PMID- 21855865
TI  - Posterior fossa syndrome in adults: a new case and comprehensive survey of the
      literature.
AB  - Although the posterior fossa syndrome (PFS) can be considered as an
      aetiologically heterogeneous condition affecting children and adults, it most
      often occurs in paediatric patients after cerebellar tumour surgery. In patients
      with a tumoural aetiology, the syndrome is typically characterised by a short
      symptom-free postoperative period followed by mutism of variable duration and
      behavioural and affective changes. More than 200 paediatric cases have been
      described but reports of adult patients are extremely rare. This paper discusses
      PFS in adults on the basis of a comprehensive literature survey and describes the
      pre- and postoperative findings in a new adult patient. In the preoperative
      phase, cognitive, behavioural and affective abnormalities were identified,
      matching a diagnosis of cerebellar cognitive affective syndrome (CCAS)
      (Schmahmann and Sherman, 1998; Schmahmann, 2004). The immediate postoperative
      course was characterised by prefrontal-like behavioural and affective
      abnormalities, peduncular hallucinations and confusion evolving to psychosis.
      Akinetic mutism subsequently developed, lasted for 12 days and then alternated
      with episodes of diminished responsiveness in which pathological laughing and
      crying (PLC) occurred. Akinetic mutism resolved after treatment with a non
      ergoline dopamine-agonist but CCAS persisted during longitudinal follow-up. From
      a semiological point of view "relapsing-remitting akinetic mutism" and PLC in our
      patient might add relevant information to current insights in the clinical
      expression of the PFS. As evidenced by a close parallelism between single photon
      emission computed tomography (SPECT) and clinical findings, CCAS as well as PFS
      seem to reflect functional disruption of the cerebello-cerebral network involved
      in cognitive, behavioural and affective functions. These findings may indicate
      that both syndromes share overt semiological resemblances and a common
      pathophysiological substrate. Consequently, CCAS and PFS may both be regarded as
      cerebellar-induced clinical conditions showing different aspects of a spectrum
      that range in degree of severity and symptom duration.

PMID- 21855866
TI  - Cancer incidence among residents of the Three Mile Island accident area: 1982
      1995.
AB  - BACKGROUND: The Pennsylvania Department of Health established a registry of the
      Three Mile Island (TMI) nuclear power plant accident in 1979. Over 93% of the
      population present on the day of the accident within a 5-mile radius was enrolled
      and interviewed. We used the registry to investigate the potential cancer risk
      from low-dose radiation exposure among the TMI population. METHODS: Cancer
      incidence data among the TMI cohort were available from 1982 to 1995. Because
      more than 97% of the population were white and few cancer cases were reported for
      those younger than 18 years of age, we included whites of age 18 years and older
      (10,446 men and 11,048 women) for further analyses. Cox regression models were
      used to estimate the relative risk (RR) per 0.1 mSv and 95% confident interval
      (CI) of cancer by radiation-related exposures. The cancers of interest were all
      malignant neoplasms, cancer of bronchus, trachea, and lung, cancer of lymphatic
      and hematopoietic tissues, leukemia, and female breast. RESULTS: Among men and
      women, there was no evidence of an increased risk for all malignant neoplasms
      among the TMI cohort exposed to higher maximum and likely gamma radiation
      (RR=1.00, 95% CI=0.97, 1.01 and RR=0.99, 95% CI=0.94, 1.03, respectively) after
      adjusting for age, gender, education, smoking, and background radiation.
      Elevation in risk was noted for cancer of the bronchus, trachea, and lung in
      relation to higher background radiation exposure (RR=1.45, 95% CI=1.02-2.05 at
      8.0-8.8 MUR/h compared to 5.2-7.2 MUR/h). An increased risk of leukemia was found
      among men exposed to higher maximum and likely gamma radiation related to TMI
      exposure during the ten days following the accident (RR=1.15, 95% CI=1.04, 1.29
      and RR=1.36, 95% CI=1.08, 1.71, respectively). This relationship was not found in
      women. CONCLUSION: Increased cancer risks from low-level radiation exposure
      within the TMI cohort were small and mostly statistically non-significant.
      However, additional follow-up on this population is warranted, especially to
      explore the increased risk of leukemia found in men.

PMID- 21855867
TI  - The incidence of deep vein thrombosis in Japanese patients undergoing endoscopic
      submucosal dissection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is more invasive than other
      common endoscopic procedures and may increase the risk for deep vein thrombosis
      (DVT)/pulmonary embolism. The incidence of DVT/pulmonary embolism after ESD has
      not been adequately studied. OBJECTIVE: To evaluate DVT incidence and disease
      specific features of D-dimer levels in ESD patients. DESIGN: Prospective cohort
      study. SETTING: Single academic center. PATIENTS: This study involved 60 patients
      with superficial gastric neoplasms indicated for ESD. INTERVENTION: For all
      patients who underwent ESD, ultrasonography of the lower limbs was performed to
      detect DVT the day after ESD. D-dimer levels were measured 3 times: before ESD,
      immediately after ESD, and the day after ESD. MAIN OUTCOME MEASUREMENTS: DVT
      incidence after ESD. RESULTS: The DVT incidence was 10.0% (6/60). At all 3 time
      points, D-dimer measurements were higher in patients with DVT than in patients
      without DVT. According to receiver operating characteristic curve analysis, the
      resulting cut-off value of the D-dimer level the day after ESD was 1.9 MUg/mL
      (sensitivity 83.3%; specificity 79.6%) for ESD patients, with superior
      association to pre-ESD or immediately after ESD. In univariate analyses, high D
      dimer levels the day after ESD and the presence of comorbidities were
      significantly associated with DVT development. LIMITATIONS: Single center and
      small number of patients. CONCLUSION: ESD procedures have a moderate risk for
      venous thromboembolism. In patients undergoing ESD, D-dimer levels, especially on
      the day after ESD, may have specific features associated with DVT development.

PMID- 21855868
TI  - Self-expandable metal stents for relieving malignant colorectal obstruction:
      short-term safety and efficacy within 30 days of stent procedure in 447 patients.
AB  - BACKGROUND: The self-expandable metal stent (SEMS) can alleviate malignant
      colonic obstruction and avoid emergency decompressive surgery. OBJECTIVE: To
      document performance, safety, and effectiveness of colorectal stents used per
      local standards of practice in patients with malignant large-bowel obstruction to
      avoid palliative stoma surgery in incurable patients (PAL) and facilitate bowel
      decompression as a bridge to surgery for curable patients (BTS). DESIGN:
      Prospective clinical cohort study. SETTING: Two global registries with 39
      academic and community centers. PATIENTS: This study involved 447 patients with
      malignant colonic obstruction who received stents (255 PAL, 182 BTS, 10 no
      indication specified). INTERVENTION: Colorectal through-the-scope SEMS placement.
      MAIN OUTCOME MEASUREMENTS: The primary endpoint was clinical success at 30 days,
      defined as the patient's ability to maintain bowel function without adverse
      events related to the procedure or stent. Secondary endpoints were procedural
      success, defined as successful stent placement in the correct position, symptoms
      of persistent or recurrent colonic obstruction, and complications. RESULTS: The
      procedural success rate was 94.8% (439/463), and the clinical success rates were
      90.5% (313/346) as assessed on a per protocol basis and 71.6% (313/437) as
      assessed on an intent-to-treat basis. Complications included 15 (3.9%)
      perforations, 3 resulting in death, 7 (1.8%) migrations, 7 (1.8%) cases of pain,
      and 2 (0.5%) cases of bleeding. LIMITATIONS: No control group. No primary
      endpoint analysis data for 25% of patients. CONCLUSION: This largest multicenter,
      prospective study of colonic SEMS placement demonstrates that colonic SEMSs are
      safe and highly effective for the short-term treatment of malignant colorectal
      obstruction, allowing most curable patients to have 1-step resection without
      stoma and providing most incurable patients minimally invasive palliation instead
      of surgery. The risk of complications, including perforation, was low.

PMID- 21855869
TI  - New appearance of a snowman-like, polypoid lesion on the major duodenal papilla
      in a patient with relapsing autoimmune pancreatitis.

PMID- 21855870
TI  - Endoscopic enucleation of large esophageal leiomyomas.

PMID- 21855871
TI  - Aortoesophageal fistula after radiation therapy for esophageal cancer (with
      video).

PMID- 21855872
TI  - Magnetic compression anastomosis is useful in biliary anastomotic strictures
      after living donor liver transplantation.
AB  - BACKGROUND: An anastomotic biliary stricture is a complication of living donor
      liver transplantation (LDLT) performed using duct-to-duct anastomosis. Despite
      advances in treating this complication, there is no one established treatment
      protocol. OBJECTIVE: To investigate the safety, effectiveness, and mid-term
      outcome of magnetic compression anastomosis (MCA) for treating biliary
      obstruction after LDLT when the obstruction cannot be resolved by using
      percutaneous or peroral methods. DESIGN: Retrospective, observational study with
      standardized treatment and follow-up. SETTING: Tertiary-care academic medical
      center. PATIENTS: Twelve patients underwent MCA procedures to treat anastomosis
      site stricture after LDLT. INTERVENTIONS: MCA. MAIN OUTCOME MEASUREMENTS: Bile
      duct patency, technique performance, and complications were evaluated. RESULTS:
      We achieved magnet approximation at the anastomotic stricture in 10 of 12
      patients (83.3%). The magnets failed to approximate in 2 patients. We achieved
      recanalization of the stricture site in 10 of 10 patients. We removed an internal
      catheter in 9 patients. The mean interval from magnet approximation to removal
      was 74.2 days (range 14-181 days). The mean time from recanalization to removal
      of the internal catheter was 183 days (range 51-266 days). Patients were examined
      regularly after removing the internal catheter with a mean follow-up period of
      331 days (range 148-581 days). The observed MCA-related complications consisted
      of 1 case of mild cholangitis and 1 recurrence of the anastomotic stricture.
      LIMITATIONS: Nonrandomized study design. CONCLUSIONS: MCA safely and effectively
      resolved post-LDLT biliary duct-to-duct anastomotic strictures that could not be
      resolved using conventional methods, such as ERCP and percutaneous transhepatic
      biliary drainage.

PMID- 21855873
TI  - Usefulness of single-balloon enteroscopy in pediatric Crohn's disease.
AB  - BACKGROUND: Single-balloon enteroscopy (SBE) has not been reported in pediatric
      Crohn's disease (CD). OBJECTIVE: To determine technical performance, yield,
      safety, and clinical impact of SBE in pediatric patients with suspected and
      established CD. DESIGN: Prospective, cohort study. SETTING: Academic tertiary
      care referral center. PATIENTS: This study involved 16 patients (group A) with
      suspected CD and unspecific upper and lower GI endoscopy results and 14 patients
      (group B) with longstanding CD with previous surgery and showing signs
      unaccountable by conventional endoscopy. All underwent magnetic resonance
      imaging, and 14 patients in group A also underwent wireless capsule endoscopy.
      INTERVENTION: SBE. MAIN OUTCOME MEASUREMENTS: SBE diagnostic and therapeutic
      yield, technical performance, clinical impact, and safety. RESULTS: In group A,
      SBE aided diagnosis of CD in 12 patients and eosinophilic enteropathy in 2
      patients, whereas no lesions were found in 2 patients. WCE was diagnostic of CD
      in 3 patients, suggestive of CD in 7 patients, and unspecific in the remaining
      patients. In group B, SBE revealed moderate-to-severe disease activity in most
      patients, leading to the introduction of or change in biological therapy, with a
      marked decrease in the pediatric Crohn's disease activity index scores. SBE
      allowed successful dilation of small-bowel strictures in 2 patients in group A
      and 3 in group B. No complications occurred. LIMITATIONS: Small sample size, no
      direct comparison with imaging or other endoscopic techniques. CONCLUSION: SBE is
      a useful and safe endoscopic procedure for evaluating the small bowel in
      pediatric patients with suspected or established CD. Not only does it allow a
      definite diagnosis of CD when the latter is uncertain, but it is also very
      effective in the management of small-bowel strictures, thus avoiding surgery. It
      may be helpful in redirecting therapy in selected CD patients.

PMID- 21855874
TI  - Optimal positioning of the DVR plate in distal radius fractures: a cadaveric
      examination of a referencing technique.
AB  - INTRODUCTION: Volar locking plates have revolutionised the treatment of distal
      radius fractures but complications are not uncommon. We present a cadaveric study
      and a technical tip to assist in the accurate and reproducible placement of one
      such plate. STUDY: We placed 25-g needles in the distal radioulnar joint and
      radiocarpal joint and measured the distance from these needles to a DVR plate in
      its optimal position. This distance measured 5mm, corresponding to the width of
      the depth gauge handle. Placing this next to needles in these joints can help pre
      plan the most distal and ulnar extent of the plate allowing for reproducible
      optimal positioning of the DVR plate. TECHNIQUE: The technique developed uses the
      existing kit and is simple and easy to build into one's existing fixation
      technique.

PMID- 21855875
TI  - Glucosamine-supplementation promotes endoplasmic reticulum stress, hepatic
      steatosis and accelerated atherogenesis in apoE-/- mice.
AB  - OBJECTIVES: To determine the effects of glucosamine-supplementation on
      endoplasmic reticulum (ER) stress levels and atherogenesis, and to investigate
      the potential role of glucosamine in hyperglycemia-associated accelerated
      atherosclerosis. METHODS: Five week old apolipoprotein E-deficient (apoE-/-) mice
      were provided with normal drinking water or water supplemented with 5%
      glucosamine (w/v) or 5% mannitol (w/v). To induce hyperglycemia, a separate group
      of apoE-/- mice received multiple low dose injections of streptozotocin (STZ).
      All mice were provided with a standard chow diet and were euthanized at 15 weeks
      of age. Hepatic and vascular ER stress levels and atherosclerotic lesion area at
      the aortic root were determined. RESULTS: STZ-induced hyperglycemic and
      glucosamine-supplemented mice had significantly larger and more advanced
      atherosclerotic lesions than control mice. Indications of ER stress were
      increased in the livers and atherosclerotic lesions of hyperglycemic and
      glucosamine-supplemented mice but not in the controls. In glucosamine
      supplemented mice accelerated atherosclerosis was independent of detectable
      changes in blood glucose concentration, glucose tolerance, plasma insulin, or
      plasma lipid levels. CONCLUSION: Similar to hyperglycemia, glucosamine
      supplementation promotes ER stress, hepatic steatosis and accelerated
      atherosclerosis. These findings support a model by which hyperglycemia promotes
      hepatic and vascular complications via a glucosamine intermediate.

PMID- 21855876
TI  - Physical (in)activity over 20 y in adulthood: associations with adult lipid
      levels in the 1958 British birth cohort.
AB  - OBJECTIVES: To investigate associations between physical (in)activity at
      different life-stages and lipids in mid-adulthood, examining the role of
      potential confounding and mediating factors, such as adiposity. METHODS: Data
      from the 1958 British birth cohort (n=7824) were examined. Using linear
      regression, we analysed prospectively reported frequency of activity and TV
      viewing (23, 33, 42 and 45 y) in relation to total, LDL-, HDL-cholesterol and
      triglycerides, at 45 y. RESULTS: Activity at different ages was associated with
      HDL-cholesterol and triglycerides at 45 y: e.g. in men, a 1 day/week greater
      activity frequency at 42 y was associated with 0.006 mmol/L higher HDL
      cholesterol and 1.4% lower triglycerides. Most associations attenuated, but were
      not entirely explained by adjustment for covariates (life-styles and socio
      economic factors): e.g. among men, the estimated 2.0% lower triglycerides per 1
      day/week greater frequency at 33 y reduced to 1.8% after adjustment. Among women,
      though not men, activity at both 23 and 45 y contributed cumulatively to HDL
      cholesterol. For sedentary behaviour, associations were found for sitting at
      work: a 1 h/day greater sitting among men was associated with a 0.012 mmol/L
      lower HDL-cholesterol after adjustment for covariates. Associations were seen for
      TV-viewing: e.g. in men, a 0.04 mmol/L lower HDL-cholesterol and 5.9% higher
      triglycerides per hour/day greater TV-viewing at 45 y, attenuated, respectively,
      to 0.03 mmol/L and 4.6% after adjustment for covariates. Associations attenuated
      further after adjustment for current BMI. Associations for total and LDL
      cholesterol were less consistent. CONCLUSION: Activity and sedentary behaviour at
      different adult ages were associated with HDL-cholesterol and triglycerides in
      mid-adulthood. Associations were partly mediated by other life-style factors and
      by BMI.

PMID- 21855877
TI  - Influence of carrier solution ionic strength and injected sample load on
      retention and recovery of natural nanoparticles using Flow Field-Flow
      Fractionation.
AB  - Natural nanoparticles, including both natural organic matter (NOM) and inorganic
      mineral-like phases, have been broadly characterized using Flow Field-Flow
      Fractionation (FlowFFF). Calibration with polystyrene sulfonate (PSS) standards
      was generally carried out in order to determine the molecular weight distribution
      of the NOM, however if the analyzed sample has a different charge density
      compared to the PSS standards, the resulting molecular weight distribution may
      become meaningless. The presented study therefore investigates and compares the
      influences of ionic strength and sample load on the retention time and recovery
      of both PSS standards and natural nanoparticles from a variety of sources. The
      minimum ionic strength in the carrier solution and the maximum injected sample
      load required for satisfactory separation depend on the molecular weight of the
      PSS standards and on the nature of the NOM. The degree to which results depend on
      conditions and parameters within the FlowFFF varies significantly between the
      different natural nanoparticle samples. We found that it may be necessary to
      calibrate the channel under different conditions from the actual sample runs.
      Under well controlled and documented conditions this could represent an important
      move away from the paradigm of "same conditions for standards and sample". From
      all conditions tested, the most reliable molecular weight calibrations were
      obtained at elevated ionic strengths in the carrier solution (>0.04 M) and low
      injected mass of PSS. However, even under these optimized conditions variations
      of up to 20% occur in the calculated molecular weights, and the recovery of NOM
      falls by up to 50% at high ionic strengths. Many applications aim for both
      correct molecular weight distribution and the measurement of low concentrations
      of elements bound to natural nanoparticles. We conclude, however, that finding
      conditions that are equally optimal for both of these analytical tasks is not
      always feasible.

PMID- 21855878
TI  - Pressure-assisted electrokinetic supercharging for the enhancement of non
      steroidal anti-inflammatory drugs.
AB  - Electrokinetic supercharging (EKS) combines field-amplified sample injection with
      transient isotachophoresis (tITP) to create a powerful on-line preconcentration
      technique for capillary electrophoresis. In this work, EKS is enhanced with a
      positive pressure (pressure-assisted EKS, or PA-EKS) during injection to improve
      stacking of non-steroidal anti-inflammatory drugs (NSAIDs). Several parameters,
      including buffer composition and concentration, terminating electrolyte, organic
      modifier, and injection voltage and injection time of both terminating
      electrolyte and sample were optimized. Detection limits for seven NSAIDs were
      determined and an enhancement in sensitivity of almost 50,000-fold was obtained.
      The PA-EKS method has the potential to be a simple MS compatible preconcentration
      method to improve the sensitivity of CE.

PMID- 21855879
TI  - Applications of superficially porous particles: high speed, high efficiency or
      both?
AB  - The new generation of superficially porous particles (SPPs) offers impressive
      chromatographic efficiency compared to totally porous particles. Specifically,
      modern sub-3-MUm SPPs generate much improved reduced plate height but at lower
      backpressure compared to sub-2-MUm totally porous particles. This feature makes
      them attractive for various types of applications and SPPs are quickly being
      adopted in many analytical laboratories. In this review, we use optimization
      theory to compare the performance limit of modern SPPs and totally porous
      particles under optimized conditions, in order to answer the question: what are
      the optimal applications for modern SPPs? Are they most suitable for fast
      separations, or for high efficiency separations, or for both? Successful examples
      of using modern SPPs in different application areas are reviewed, over a wide
      range of sample complexity and analysis time. Practical aspects of the use of
      such particles and future development possibilities are also discussed.

PMID- 21855880
TI  - Estimation of molecular diffusivity in liquid phase systems by the Wilke-Chang
      equation.
AB  - This study deals with the application of the Wilke-Chang equation to the
      estimation of molecular diffusivity (Dm) in liquid phase systems including polar
      solutes and/or solvents. First, Dm of benzene in six different organic solvents
      was experimentally measured by the peak parking method. The value of association
      coefficient (alpha) was calculated from the Dm values by assuming that Dm can be
      represented by the Wilke-Chang equation. Then, the alpha value was correlated
      with the solubility parameter (delta) and ET of the solvents. Two different
      curved correlations were observed between alpha and the two physico-chemical
      parameters. This means that alpha of given solutes and solvents can be obtained
      from the values of delta and/or ET. Finally, Dm was estimated by a modified Wilke
      Chang equation, which is derived by considering the aggregation of not only
      solvent molecules but also solute molecules. Although alpha is necessary for the
      estimation, it was calculated from delta for various solutes and solvents. The Dm
      values estimated were compared with those reported in literature. The mean square
      deviation between the Dm values was calculated less than 19% for 71 Dm data. It
      was demonstrated that the modified Wilke-Chang equation can be used for
      estimating Dm in liquid phase systems containing polar solutes and solvents.

PMID- 21855881
TI  - Composition and molecular weight analysis of styrene-acrylic copolymers using
      thermal field-flow fractionation.
AB  - Thermal field-flow fractionation coupled with online multiangle light scattering,
      differential refractive index and quasielastic light scattering (ThFFF
      MALS/dRI/QELS) was used to simultaneously determine the molecular weight (MW) and
      composition of polystyrene-poly(n-butyl acrylate) (PS-PBA) and polystyrene
      poly(methyl acrylate) (PS-PMA) copolymers. The online measurement of the normal
      diffusion coefficient (D) by QELS allowed calculation of the copolymer thermal
      diffusion coefficient (D(T)) of sample components as they eluted from the ThFFF
      channel. DT was found to be independent of MW for copolymers with similar
      compositions and dependent on composition for copolymers with similar MW in a non
      selective solvent. By using a solvent that is non-selective to both blocks of the
      copolymer, it was possible to establish a universal calibration plot of DT versus
      mole fraction of one of the monomer chemistries comprising the copolymer. PS-PBA
      and PS-PMA linear diblock polymers were determined to vary in composition from
      100/0 to 20/80 wt% PS/acrylate and ranged in MWs between 30 and 360 kDa. The
      analysis of a PS-PBA miktoarm star copolymer revealed a polydisperse material
      with a weight percent PBA of 50-75% and MW ranging from 100 to 900 kDa. The
      presented ThFFF-MALS/dRI/QELS method allowed rapid characterization of polymers
      with MW and chemical distributions in a single analysis.

PMID- 21855882
TI  - Identification of impurities in artemisinin, their behavior in high performance
      liquid chromatography and implications for the quality of derived anti-malarial
      drugs.
AB  - Previous work [1] on the HPLC analysis of artemisinin tentatively identified the
      two impurities present above trace levels. This identification was based on LC-MS
      results and NMR of impurities isolated from artemisinin. In this work the
      impurities have been synthesized allowing verification of their identity by LC
      MS. It is found that the previously suggested elution order is incorrect. A
      determination of relative response factors strongly impacts suggested limits on
      impurity levels and explains the erroneous peak assignment. The fates of the
      identified impurities are explored in the transformation of artemisinin to its
      derivative active pharmaceutical ingredients. A survey of a wide variety of
      artemisinin samples isolated from different geographical regions, different
      growing seasons, different plant backgrounds and using different extraction and
      purification approaches showed that artemisinin has sufficient purity for its
      intended use as a raw material for anti-malarial drug products.

PMID- 21855883
TI  - Use of triacylglycerol profiles established by high performance liquid
      chromatography with ultraviolet-visible detection to predict the botanical origin
      of vegetable oils.
AB  - A method for the determination of triacylglycerols (TAGs) in vegetable oils from
      different botanical origins by HPLC with UV-vis detection has been developed.
      Using a core-shell particle packed column (C18, 2.6 MUm), TAG separation was
      optimized in terms of mobile phase composition and column temperature. Using
      isocratic elution with acetonitrile/n-pentanol at 10  degrees C, excellent
      efficiency with good resolution between most of the TAG peak pairs, within a
      total analysis time of 15 min, was achieved. Using mass spectrometry detection, a
      total of 15 peaks, which were common to oils of six different botanical origins
      (corn, extra virgin olive, grapeseed, hazelnut, peanut and soybean) were
      identified. These peaks were used to construct linear discriminant analysis (LDA)
      models for botanical origin prediction. Ratios of the peak areas selected by
      pairs were used as predictors. All the oils were correctly classified with
      assignment probabilities higher than 95%.

PMID- 21855884
TI  - Effect of the graft chain length and density on the morphology of radiation
      modified polysilane monolayers at the air/water interface.
AB  - The variation in the morphology of monolayers at the air/water interface is
      investigated for two kinds of radiation-modified polysilanes with different
      structures: poly(diethyl fumarate)-grafted poly(methyl-n-propylsilane) (PMPrS-g
      PDEF) and maleic anhydride-grafted PMPrS (PMPrS-g-MAH). PMPrS-g-PDEF has long but
      sparsely-attached PDEF graft chains, while PMPrS-g-MAH has short but densely
      attached MAH graft units. Surface pressure-area measurements indicate that PMPrS
      g-PDEF monolayers extensively spread at the air/water interface though PMPrS
      homopolymer hardly spreads. AFM observation reveals that PMPrS-g-PDEF monolayers
      have an inhomogeneous structure containing string-like microstructures. This
      result suggests that PMPrS main chains are detached from the water surface to
      aggregate together and only PDEF chains spread over the water surface. In
      contrast, PMPrS-g-MAH forms uniform monolayers with a smooth surface. PMPrS main
      chains of PMPrS-g-MAH are anchored to the water surface by densely grafted MAH
      units. It is also demonstrated that only the PMPrS-g-MAH monolayers are
      successfully deposited layer-by-layer on a solid substrate by the Y-type
      deposition.

PMID- 21855886
TI  - In situ ligand exchange of thiol-capped CuInS2/ZnS quantum dots at growth stage
      without affecting luminescent characteristics.
AB  - An aliphatic thiol ligand of CuInS(2)/ZnS core/shell quantum dots is replaced
      with a hydroxyl-terminated thiol ligand by utilizing 'on-off state' of ligands
      during growth stage of the quantum dots. After the ligand-exchange, negligible
      differences were observed on both photoluminescence spectrum and luminescent
      quantum efficiency. The reason for the high retention of luminescent efficiency
      comes from no local agglomeration and no surface deterioration of QDs. It is also
      observed that 70% of initial ligands are exchanged by the replacing ligand,
      determined by FT-IR and (1)H NMR. The proposed method provides the quantum dots
      with an excellent dispersibility in polar solvents, supported by identical
      luminescence decay characteristics of the QDs.

PMID- 21855885
TI  - Positive cooperative mechanistic binding of proteins at low concentrations: a
      comparison of poly (sodium N-undecanoyl sulfate) and sodium dodecyl sulfate.
AB  - The interactions of the negatively charged achiral molecular micelle, poly
      (sodium N-undecanoyl sulfate) (poly-SUS), with four different proteins using
      intrinsic and extrinsic fluorescence spectroscopic probes, are studied. A
      comparison of poly-SUS with the conventional surfactant, sodium dodecyl sulfate
      (SDS), and the monomeric species, SUS, is also reported. In this work, we
      observed that poly-SUS preferentially binds to acidic proteins, exhibiting
      positive cooperativity at concentrations less than 1 mM for all proteins studied.
      Moreover, it appears that the hydrophobic microdomain formed through
      polymerization of the terminal vinyl group of the monomer, SUS, is largely
      responsible for the superior binding capacity of poly-SUS. From these results, we
      conclude that the interactions of poly-SUS with the acidic proteins are
      predominantly hydrophobic and postulate that poly-SUS would produce superior
      interactions relative to SDS at low concentrations in polyacrylamide gel
      electrophoresis (PAGE). As predicted, use of poly-SUS allowed separation of the
      His-tagged tumor suppressor protein, p53, at sample buffer concentrations as low
      as 0.08% w/v (2.9 mM), which is 24 times lower than required for SDS in the
      standard reducing PAGE protocol. This work highlights the use of poly-SUS as an
      effective surfactant in 1D biochemical analysis.

PMID- 21855887
TI  - Benzalkonium chloride and sulfamethoxazole adsorption onto natural
      clinoptilolite: effect of time, ionic strength, pH and temperature.
AB  - The influence of different physical factors on the adsorption of the cationic
      surfactant benzalkonium chloride (BC) and the model drug sulfamethoxazole by a
      purified natural clinoptilolite (NZ) has been studied in order to employ zeolite
      surfactant-drug composites as drug deliverer. It has been demonstrated that the
      adsorption of BC and sulfamethoxazole onto NZ depends of the time, the
      temperature, the ionic strength and the pH of the aqueous medium. The optimal
      conditions for the preparation of the zeolite-surfactant and zeolite-surfactant
      drug composite materials are established. The results of the composite
      characterization support the presence of BC and sulfamethoxazole, as well as the
      structural stability of NZ during the treatments performed. The release
      experiments in acid medium demonstrate that the adsorption of sulfamethoxazole is
      reversible. It is also confirmed that the drug release profile corresponds to a
      diffusion or zero-order mechanism as a function of the compression pressure.

PMID- 21855888
TI  - Primary charge effects on prolate spheroids with moderate aspect ratios.
AB  - In this article, we investigate the behavior of charged spheroidal colloids with
      moderate aspect ratios in linear flow fields. We use direct numerical simulation
      with body-fitted grids for the solution of the Stokes-Poisson-Nernst-Planck
      system to include all non-linear effects. Therefore, we propose an efficient semi
      implicit time discretization based on a splitting of the Stokes equation. We will
      study the effects of the electric double layer on the forces, torques and on the
      motion of spheroidal particles. For low Reynolds numbers, we find approximating
      linear expressions between the ambient fluid flow and the force and torque on the
      particle. The description of this linear behavior is based on the resistance
      functions, whose dependencies on the Debye length and the zeta potential are
      investigated. It is recovered that the resistance functions obey a quadratic
      dependence on the zeta potential in the small zeta potential regime. For low
      values of the zeta potential, approximate formulas for the resistance functions
      are given. The approximation properties are carefully studied by comparing the
      approximate results with direct numerical simulations. For the case of a shear
      flow, the approximate formulas can be used to avoid time-consuming direct
      numerical simulations.

PMID- 21855889
TI  - Ultra lightweight PMMA-based composite plates with robust super-hydrophobic
      surfaces.
AB  - Extremely lightweight plates made of an engineered PMMA-based composite material
      loaded with hollow glass micro-sized spheres, nano-sized silica particles and
      aluminum hydroxide prismatic micro-flakes were realized by cast molding. Their
      interesting bulk mechanical properties were combined to properly tailored surface
      topography compatible with the achievement of a superhydrophobic behavior after
      the deposition of a specifically designed hydrophobic coating. With this aim, we
      synthesized two different species of fluoromethacrylic polymers functionalized
      with methoxysilane anchoring groups to be covalently grafted onto the surface
      protruding inorganic fillers. By modulating the feed composition of the reacting
      monomers, it was possible to combine the hydrophobic character of the polymer
      with an high adhesion strength to the substrate and hence to maximize both the
      water contact angle (up to 157 degrees ) and the durability of the easy-to-clean
      effect (up to 2000 h long outdoor exposure).

PMID- 21855890
TI  - Aniline as a dispersing and stabilizing agent for reduced graphene oxide and its
      subsequent decoration with Ag nanoparticles for enzymeless hydrogen peroxide
      detection.
AB  - An aqueous dispersion of reduced graphene oxide (rGO) has been successfully
      prepared via chemical reduction of graphene oxide (GO) by hydrazine hydrate in
      the presence of aniline for the first time. The noncovalent functionalization of
      rGO by aniline leads to a rGO dispersion that can be very stable for several
      months without the observation of any floating or precipitated particles. Several
      analytical techniques including Raman spectroscopy and X-ray photoelectron
      spectroscopy (XPS) have been used to characterize the resulting rGO. Taking
      advantages of the fact reducing ability of aniline toward AgNO(3), we further
      demonstrated the subsequent decoration of rGO with Ag nanoparticles (AgNPs) by in
      situ chemical reduction of silver salts. It was found that such AgNP/rGO
      nanocomposites exhibit good catalytic activity toward the reduction of hydrogen
      peroxide (H(2)O(2)), leading to an enzymeless sensor with a fast amperometric
      response time of less than 2s. The linear detection range is estimated to be from
      100 MUM to 80 mM (r=0.9991), and the detection limit is estimated to be 7.1 MUM
      at a signal-to-noise ratio of 3.

PMID- 21855891
TI  - Kinetic properties of pancreatic and intestinal sPLA2 from chicken and mammals
      using the monomolecular film technique.
AB  - The interfacial kinetic and binding data for the pancreatic and intestinal sPLA2
      from bird and mammals show that these enzymes have dramatically different ability
      to bind and hydrolyse phospholipids. The main conclusions from our experimental
      data indicate that phosphatidylcholine monolayers (PC), in contrast to
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), were resistant to
      the hydrolysis by human intestinal sPLA2. Conversely, chicken intestinal sPLA2
      was found to be able to hydrolyse all the phospholipids tested, including PC. The
      experiments show also that the interfacial penetrating ability of chicken sPLA2
      (from intestine and pancreas) was higher than their mammalian's orthologs. This
      observation is confirmed by the activity of pancreatic chicken PLA2 measured on
      PC film showing that the interfacial pressure window that permits sPLA2 activity
      was very large, between 5 and 20 dynes cm(-1), compared with the porcine
      pancreatic sPLA2-IB which was inactive at pressure above 15 dynes cm(-1). In
      trying to establish a structure-function relationship, we examined the surface
      electrostatic potentials of the various sPLA2 from chicken and mammals. We
      reported in this study that the binding, orientation and persistence of sPLA2 at
      the lipid-water interface is probably governed by the electrostatic and
      hydrophobic forces operative at this surface. These variations argue strongly
      that these enzymes are not isoforms and that they are expected to have functions
      other than the release of lipid mediators for the biosynthesis of the
      eicosanoids.

PMID- 21855892
TI  - Effect of pH on the single-step synthesis of gold nanoparticles using PEO-PPO-PEO
      triblock copolymers in aqueous media.
AB  - The influence of pH value on gold nanoparticle production in the presence of
      Pluronic stabilizers is systematically investigated. The reactions are studied as
      a function of pH and at fixed concentrations of the two reactants, HAuCl(4) and
      P123 block copolymer. Results indicate that the reaction pathway during the
      nanoparticle formation can be controlled by varying pH. The nanoparticles
      synthesized at pH=11.12 have an average diameter of 9.6 nm with a narrow size
      distribution, and the Pluronics are adsorbed on individual gold particle surfaces
      to form core-shell structures via hydrophobic interactions. The present work
      provides an economic way to improve the dispersion and stabilization of gold
      nanoparticles and throws further light on the understanding of gold nanoparticle
      production using block copolymers.

PMID- 21855893
TI  - How do young children's spatio-symbolic skills change over short time scales?
AB  - Three experiments were designed to examine how experience affects young
      children's spatio-symbolic skills over short time scales. Spatio-symbolic
      reasoning refers to the ability to interpret and use spatial relations, such as
      those encountered on a map, to solve symbolic tasks. We designed three tasks in
      which the featural and spatial correspondences between a map and its referent (a
      model) were systematically manipulated using a map-model paradigm. We explored
      how 2.5- to 5-year-olds learn to map spatial arrays when both identical and
      unique correspondences coexist (Experiment 1), when featural cues are absent
      (Experiment 2), and when object and location similarities are contradictory,
      thereby making both featural and spatial mapping strategies distinct (Experiment
      3). Although younger children have a stronger tendency to focus on object (or
      featural) cues, even 2.5-year-olds can appreciate a symbol beyond the level of
      object similarity. With age, children are increasingly capable of learning to use
      spatio-relational mapping and of discovering a spatio-symbolic mapping strategy
      to solve more challenging map use tasks over short time scales.

PMID- 21855894
TI  - Symptomatic viral infection is associated with impaired response to treatment in
      children with acute asthma.
AB  - OBJECTIVE: To examine the influence of viral respiratory infection (VRI) on
      treatment response in acute asthma in children. STUDY DESIGN: A total of 218
      children (mean age, 6.6 years) with acute asthma were recruited. Symptoms were
      recorded, an asthma severity score was determined, and whenever possible, a per
      nasal aspirate was obtained for detection of viruses. Each child's response to
      inhaled beta(2)-agonists was assessed after 6, 12, and 24 hours. RESULTS: The 168
      children with VRI symptoms received more treatment with inhaled beta(2)-agonists
      after 6 hours (P = .010), 12 hours (P = .002), and 24 hours (P = .0005) compared
      with the 50 children without such symptoms. Asthma severity did not differ
      between the 2 groups. A per-nasal aspirate was obtained from 77% of the children.
      The most frequently identified virus was rhinovirus (61.4%). Among children with
      symptoms of a VRI, those with rhinovirus had an impaired response to beta(2)
      agonists at 6 hours (P = .032). CONCLUSION: Children with acute asthma and
      symptoms of VRI respond less effectively to beta(2)-agonists after 6, 12, or 24
      hours and thus may benefit from more intense therapy and monitoring.

PMID- 21855895
TI  - Localization of the subthalamic nucleus in Parkinson disease using multiunit
      activity.
AB  - BACKGROUND: Refinement of the subthalamic nucleus (STN) coordinates using
      intraoperative microelectrode recordings (MER) is routinely performed during deep
      brain stimulation (DBS) surgeries in Parkinson disease (PD). The commonly used
      criteria for electrophysiological localization of the STN are qualitative. The
      goal of this study was to validate quantitative STN detection algorithm (QD)
      derived from the multi-unit activity in a prospective setting. METHODS: Ten PD
      patients underwent STN DBS surgery. The MUA was obtained by removing large spikes
      close to microelectrode using wavelet method and integrating the 500-2000Hz band
      in the power spectral density. The qualitative intraoperative mapping of the STN
      using MER (IOM) versus QD was compared using Bland-Altman and Pearson's
      correlation analysis. RESULTS: The clinical efficacy was confirmed in all
      subjects. The mean difference between IOM and QD of the dorsal/ventral border was
      0.31+/-0.84/0.44+/-0.47mm. Using Bland-Altman statistic, only 2/36 (5.6%)
      differences (one for the dorsal border and one for the ventral border) were out
      of +/-2 sd line of measurement differences. Correlation between dorsal
      border/ventral border positions obtained by IOM and QD was 0.79, p<0.0001/0.91,
      p<0.0001. CONCLUSION: Both methods are in reasonable agreement and are strongly
      correlated. The QD gives objective coordinates of the STN borders at high
      precision and may be more accurate than IOM. Prospective blinded comparative
      studies where the DBS leads will be placed using either QD or IOM are warranted.

PMID- 21855896
TI  - The impact of low preoperative fat-free body mass on infections and length of
      stay after cardiac surgery: a prospective cohort study.
AB  - OBJECTIVE: Several studies have shown low fat-free mass index to be a stronger
      predictor for mortality than low body mass index. The main aim of this study was
      to assess the still unknown association between preoperative low fat-free mass
      index and adverse cardiac surgical outcomes. METHODS: In a prospective
      observational study, fat-free mass index was determined by bioelectric impedance
      spectroscopy on hospital admission. Associations between low fat-free mass index
      and postoperative infections and mortality, as well as prolonged intensive care
      unit and hospital stays, were analyzed with logistic and Cox regression
      techniques. RESULTS: Between February 2008 and December 2009, 325 adult patients
      admitted for elective heart surgery were included. Analyses showed that low fat
      free mass index, present in 8.3% of patients, was independently associated with
      occurrence of infections after cardiac surgery (18.5% vs 4.7%; adjusted odds
      ratio, 6.9; 95% confidence interval, 1.8-27.7; P = .01). Low fat-free mass index
      also tended to be associated with higher risk of longer postoperative intensive
      care unit stay (adjusted hazard ratio, 0.7; 95% confidence interval, 0.4-1.1; P =
      .09). When classifying patients as undernourished by traditional methods (body
      mass index <=21.0 kg/m(2) or >=10% weight loss in preceding 6 months), half of
      patients with low fat-free mass index were misclassified as well nourished.
      CONCLUSIONS: Low fat-free mass index is associated with increased occurrence of
      adverse outcomes after cardiac surgery. We advocate fat-free mass index as the
      leading parameter in classifying and treating undernourished cardiac surgical
      patients, which might improve recovery rates after cardiac surgery.

PMID- 21855897
TI  - Intrauterine rupture of anterior tricuspid valve papillary muscle: tricuspid
      valve chordae replacement on the first day of life.

PMID- 21855899
TI  - Mitral regurgitation surgery in patients with ischemic cardiomyopathy and
      ischemic mitral regurgitation: factors that influence survival.
AB  - OBJECTIVE: The treatment of patients with ischemic cardiomyopathy and concomitant
      mitral regurgitation can be challenging and is associated with reduced long-term
      survival. It is unclear how mitral valve repair versus replacement affects
      subsequent outcome. Therefore, we conducted this study to understand the
      predictors of mortality and to delineate the role of mitral valve repair versus
      replacement in this high-risk population. METHODS: From 1993 to 2007, 431
      patients (mean age, 70 +/- 9 years) with ischemic cardiomyopathy (left
      ventricular ejection fraction <= 45%) and significant ischemic mitral
      regurgitation (>2) were identified. Patients (44) with concomitant mitral
      stenosis were excluded from the analysis. A homogeneous group of 387 patients
      underwent combined coronary artery bypass grafting and mitral valve surgery,
      mitral valve repair in 302 (78%) and mitral valve replacement in 85 (22%). Uni-
      and multivariate analyses were performed on the entire cohort, and the predictors
      of mortality were identified in 2 distinct risk phases. Furthermore, we
      specifically examined the impact of mitral valve repair versus replacement by
      comparing 2 propensity-matched subgroups. RESULTS: Follow-up was 100% complete
      (median, 3.6 years; range, 0-15 years). Overall 1-, 5-, and 10-year survivals
      were 82.7%, 55.2%, and 24.3%, respectively, for the entire group. The risk
      factors for an increased mortality within the first year of surgery included
      previous coronary artery bypass grafting (hazard ratio = 3.39; P < .001),
      emergency/urgent status (hazard ratio = 2.08; P = .007), age (hazard ratio = 1.5;
      P = .03), and low left ventricular ejection fraction (hazard ratio = 1.31; P =
      .026). Thereafter, only age (hazard ratio = 1.58; P < .001), diabetes (hazard
      ratio = 2.5; P = .001), and preoperative renal insufficiency (hazard ratio =
      1.72; P = .025) were predictive. The status of mitral valve repair versus
      replacement did not influence survival, and this was confirmed by comparable
      survival in propensity-matched analyses. CONCLUSIONS: Survival after combined
      coronary artery bypass grafting and mitral valve surgery in patients with
      ischemic cardiomyopathy (left ventricular ejection fraction <= 45%) and mitral
      regurgitation is compromised and mostly influenced by factors related to the
      patient's condition at the time of surgery. The specifics of mitral valve repair
      versus replacement did not seem to affect survival.

PMID- 21855900
TI  - Association between body mass index and urolithiasis in children.
AB  - PURPOSE: The prevalence of obesity and urolithiasis in children has increased
      with time. We evaluated the relationship between body mass and urolithiasis in
      children. MATERIALS AND METHODS: We performed a matched case-control study in a
      network of 30 primary care pediatric practices. Cases included subjects with ICD
      9 codes for urolithiasis and controls were matched on age, duration of
      observation before the index date and clinical practice. Age and sex specific
      body mass index z scores at the time of the stone episode were calculated.
      Continuous body mass index z scores and clinical weight categories were evaluated
      with covariates, including race, ethnicity, gender and payer status. The OR and
      95% CI were calculated using multivariate conditional logistic regression.
      RESULTS: We identified 110 cases and 396 matched controls, of whom 1.9% and 4.3%
      were overweight, and 3.7% and 4.5% were obese, respectively. On multivariate
      conditional logistic regression analysis the continuous body mass index z score
      (OR 0.84, 95% CI 0.63-1.12, p = 0.18), overweight status (OR 0.13, 95% CI 0.01
      1.18) and obese status (OR 0.18, 95% CI 0.02-1.40) were not associated with
      urolithiasis. However, black race (OR 0.35, 95% CI 0.15-0.85) and Medicaid payer
      status (OR 0.47, 95% CI 0.24-0.93) were associated with a significant decrease in
      the odds of urolithiasis. CONCLUSIONS: High body mass was not associated with
      urolithiasis in our primary care pediatric practice network. However, black race
      and Medicaid payer status were associated with decreased odds of urolithiasis.

PMID- 21855901
TI  - Yolk sac tumor of the testis.

PMID- 21855903
TI  - Acid-sensing channels in human bladder: expression, function and alterations
      during bladder pain syndrome.
AB  - PURPOSE: We examined the possible role of H(+) activated acid-sensing ion
      channels in pain perception. We characterized expression in bladder dome biopsies
      from patients with bladder pain syndrome and controls, in cultured human
      urothelium and in urothelial TEU-2 cells. MATERIALS AND METHODS: Cold cut
      biopsies from the bladder dome were obtained in 8 asymptomatic controls and 28
      patients with bladder pain syndrome symptoms. Acid-sensing ion channel expression
      was analyzed by quantitative real-time polymerase chain reaction and
      immunofluorescence. Channel function was measured by electrophysiology. RESULTS:
      Acid-sensing ion channel 1a, 2a and 3 mRNA was detected in the human bladder.
      Similar amounts of acid-sensing ion channel 1a and 3 were detected in detrusor
      smooth muscle while in urothelium acid-sensing ion channel 3 levels were higher
      than levels of acid-sensing ion channel 1a. Acid-sensing ion channel 2a mRNA
      levels were lower than acid-sensing ion channel 1a and 3 levels in each layer.
      Acid-sensing ion channel currents were measured in TEU-2 cells and in primary
      cultures of human urothelium. Activated acid-sensing ion channel expression was
      confirmed by quantitative real-time polymerase chain reaction. TEU-2 cell
      differentiation caused acid-sensing ion channel 2a and 3 mRNA up-regulation, and
      acid-sensing ion channel 1a mRNA down-regulation. Patients with bladder pain
      syndrome showed up-regulation of acid-sensing ion channel 2a and 3 mRNA but acid
      sensing ion channel 1a remained unchanged. In contrast, transient receptor
      potential vanilloid 1 mRNA was down-regulated during bladder pain syndrome. All
      differences were statistically significant (p <0.05). CONCLUSIONS: Several acid
      sensing ion channel subunits are expressed in human bladder and TEU-2 cells, in
      which levels are regulated during urothelial differentiation. Up-regulation of
      acid-sensing ion channel 2a and 3 in patients with bladder pain syndrome suggests
      involvement in increased pain and hyperalgesia. Down-regulation of transient
      receptor potential vanilloid 1 mRNA might indicate that a different regulatory
      mechanism controls its expression in the human bladder.

PMID- 21855904
TI  - Central role of Boari bladder flap and downward nephropexy in upper ureteral
      reconstruction.
AB  - PURPOSE: We defined the role of the Boari bladder flap procedure with or without
      downward nephropexy for proximal vs distal ureteral strictures. MATERIALS AND
      METHODS: We retrospectively reviewed the records of all patients who underwent
      open ureteral reconstruction for refractory ureteral strictures, as done by a
      single surgeon between 2007 and 2010. Patients were grouped by stricture site
      into group 1--proximal third of the ureter and group 2--distal two-thirds.
      Operative techniques and outcomes were reviewed. RESULTS: During the 30-month
      study period a total of 29 ureteral reconstruction procedures were performed on
      27 patients. A Boari bladder flap was used in 10 of the 12 patients (83%) in
      group 1 and 10 of the 17 (59%) in group 2. Concomitant downward nephropexy was
      done more commonly in group 1 (58% vs 12%, p = 0.014). At a mean followup of 11.4
      months there was no difference in the overall failure rate between groups 1 and 2
      (17% vs 12%). Complications developed more frequently in group 1 (75% vs 35%, p =
      0.060), hospital stay was longer (mean 8.0 vs 4.4 days, p = 0.017) and mean
      estimated blood loss was greater (447 vs 224 ml, p = 0.008). CONCLUSIONS: The
      Boari bladder flap procedure is a reliable technique to reconstruct ureteral
      strictures regardless of site. Renal mobilization with downward nephropexy is a
      useful adjunctive maneuver for proximal strictures.

PMID- 21855905
TI  - Risk of serious falls associated with oxybutynin and tolterodine: a population
      based study.
AB  - PURPOSE: We compared the short-term risk of falls among recipients of oxybutynin
      or tolterodine to treat urinary incontinence. MATERIALS AND METHODS: We conducted
      a population based, retrospective cohort study with propensity score matching
      among patients 66 years old or older who commenced treatment with oxybutynin or
      tolterodine in Ontario, Canada. The primary outcome was a hospital visit for a
      fall within 90 days of drug initiation. Secondary outcomes included hospital
      visits for fractures, delirium or all cause mortality. RESULTS: We found no
      difference in the risk of falls among users of oxybutynin vs tolterodine
      (adjusted hazard ratio 1.04, 95% CI 0.95 to 1.14). Secondary analyses revealed no
      differential risk of fractures (aHR 0.96, 95% CI 0.82 to 1.13) or delirium (aHR
      0.90, 95% CI 0.66 to 1.23) associated with oxybutynin. However, statistically
      significant increases in the risk of all cause hospitalization (aHR 1.12, 95% CI
      1.07 to 1.17) and death (aHR 1.20, 95% CI 1.07 to 1.35) were seen with
      oxybutynin. CONCLUSIONS: Oxybutynin was not associated with a short-term
      increased risk of hospital visit for falls, fractures or delirium compared to
      tolterodine. Further research is needed to confirm whether oxybutynin is
      associated with an increased risk of hospitalization or death.

PMID- 21855906
TI  - Laparoscopic single site surgery: initial experience and description of
      techniques in the pediatric population.
AB  - PURPOSE: Recently new approaches to laparoscopic surgery, named natural orifice
      transluminal endoscopy and laparoendoscopic single site surgery, have been
      proposed to improve the cosmesis and decrease the morbidity associated with
      multiple ports sites. Experience with laparoendoscopic single site surgery
      technique in pediatric urology is still limited. We present our initial results
      with this technique in children. MATERIALS AND METHODS: Since laparoendoscopic
      single site surgery received Food and Drug Administration approval, 11 patients
      have undergone a total of 14 procedures at our department, including nephrectomy
      due to nonfunctioning kidneys in 4, removal of bilateral intra-abdominal gonads
      in 2, unilateral varicocelectomy in 4 and bilateral varicocelectomy in 1. In all
      patients a multi-channel single laparoscopic port inserted through a 2 cm skin
      incision was used to achieve access to the abdominal cavity. RESULTS: All
      patients underwent laparoendoscopic single site surgery without complications
      within a reasonable operative time. None required conversion to open or
      conventional laparoscopic surgery. All except 1 patient were discharged home on
      the day of surgery or the day after surgery. CONCLUSIONS: Our initial data show
      that laparoendoscopic single site surgery is an effective technique for various
      pediatric and adolescent urology indications. Further application of this
      procedure in a large patient group will show whether there is a place for
      laparoendoscopic single site surgery in the pediatric urology surgical
      armamentarium.

PMID- 21855907
TI  - Transition of care to an adult spina bifida clinic: patient perspectives and
      medical outcomes.
AB  - PURPOSE: Transitioning care of patients with spina bifida to adult centers poses
      a challenge. We sought patient and parent perspectives on the transition process
      at our center and correlated these perspectives with medical outcomes. MATERIALS
      AND METHODS: Patients who attended the adult spina bifida clinic at our
      institution were invited to complete SF-36(r), the Ambulatory Care Experience
      Survey and a Transition of Care Survey. Urological and neurosurgical medical
      outcomes were correlated with health status, clinic experience and perspectives
      on the transition process. Statistical analysis was done using SPSS(r), version
      16.0. RESULTS: Of 105 patients with spina bifida 24 participated in the study. SF
      36 results showed that the physical health domain correlated with lack of
      employment (p = 0.006). Patients whose parents completed the surveys on their
      behalf were more likely to have physical limitations than the patients who
      completed surveys (p = 0.011). Urological and neurosurgical outcomes did not
      significantly affect SF-36, Ambulatory Care Experience Survey or Transition of
      Care Survey scores in this patient population. Patients and caregivers identified
      similar key elements and barriers in the transition process. Satisfaction with
      care at the pediatric center was higher than at the adult center. CONCLUSIONS:
      Transitioning care of patients with spina bifida from pediatric to adult care
      poses challenges for the health care system. Medical outcomes do not impact the
      patient perspective of the transition process. To optimize the transition of care
      we must address the barriers identified by patients and their caregivers.

PMID- 21855908
TI  - Use of the ureteral access sheath during ureteroscopy in children.
AB  - PURPOSE: The use of ureteral access sheaths during ureteroscopy is common but
      there are sparse data on the safety and outcomes of ureteral access sheath use in
      children. We compared the outcomes of ureteroscopy with vs without a ureteral
      access sheath in children. MATERIALS AND METHODS: We retrospectively reviewed all
      ureteroscopy procedures for urolithiasis in patients younger than 21 years at our
      hospital from 1999 to 2009. The primary outcome was intraoperative complications.
      Secondary outcomes were postoperative hydronephrosis, emergency room
      visit/hospital readmission within 90 days, stone-free status and need for re
      treatment. We analyzed associations of a ureteral access sheath with outcomes.
      RESULTS: A total of 34 boys and 62 girls with a mean age of 13 years underwent
      ureteroscopy. A ureteral access sheath was used in 40 of the 96 patients (42%).
      The mean stone burden was 9.6 mm. Median followup was 11 months (range 0.2 to
      110). Intraoperative complication occurred in 7 cases, including
      perforation/extravasation in 4, a submucosal wire in 2 and stent migration in 1.
      Intraoperative complications were more common when a sheath was used (15% vs 2%,
      adjusted OR 8.2, 95% CI 1.3-50.9, p = 0.02). Postoperative hydronephrosis was
      observed in 7 of 73 cases (10%) but it was not significantly more common when a
      sheath was used. No ureteral stricture was identified. Sheath use was not
      associated with postoperative telephone calls, emergency room visits or
      rehospitalization. Although the stone-free rate tended to be higher in cases
      without a sheath (78% vs 59%, p = 0.09), this association was not significant in
      a multivariate model (p = 0.6). CONCLUSIONS: Although intraoperative
      complications occur more commonly during ureteroscopy with a ureteral access
      sheath, no increase in longer term adverse effects were observed. Future
      prospective studies of ureteral access sheath use in children with longer
      followup are warranted.

PMID- 21855911
TI  - The combination of Serenoa repens, selenium and lycopene is more effective than
      serenoa repens alone to prevent hormone dependent prostatic growth.
AB  - PURPOSE: Serenoa repens is frequently combined with other natural compounds, such
      as the carotenoid lycopene and the essential trace element Se, to increase its
      therapeutic activity in benign prostatic hyperplasia. We noted that the lycopene
      Se-Serenoa repens combination has greater, enhanced anti-inflammatory activity,
      which might be of particular interest for benign prostatic hyperplasia treatment.
      Testosterone administration in rats is a suitable tool for investigating hormone
      dependent benign prostatic hyperplasia. We performed a comparison experiment
      between Serenoa repens and the lycopene-Se-Serenoa repens combination on prostate
      growth induced in rats by testosterone administration. MATERIALS AND METHODS:
      Rats were treated daily with testosterone propionate (3 mg/kg subcutaneously) or
      its vehicle for 14 days. Testosterone administered animals were randomized to
      receive vehicle, Serenoa repens (25 mg/kg subcutaneously) or the combination of
      lycopene (3 mg/kg subcutaneously), Se (3 mg/kg subcutaneously) and Serenoa repens
      for 14 days. The rats were sacrificed and the prostate was removed for analysis.
      RESULTS: Lycopene-Se-Serenoa repens was more effective than Serenoa repens alone
      for decreasing prostate weight and hyperplasia, augmenting pro-apoptotic Bax and
      caspase-9, and blunting anti-apoptotic Bcl-2 mRNA. Lycopene-Se-Serenoa repens
      also markedly decreased epidermal growth factor and vascular endothelial growth
      factor expression. CONCLUSIONS: The data indicate that the lycopene-Se-Serenoa
      repens combination is superior to Serenoa repens alone for decreasing hormone
      dependent prostatic growth.

PMID- 21855912
TI  - Effects of ovariectomy and estrogen replacement on the urethral continence reflex
      during sneezing in rats.
AB  - PURPOSE: Stress urinary incontinence is often seen in postmenopausal women but
      limited information is available on hormone dependent changes of urethral
      function. Thus, we examined how ovariectomy and estrogen replacement affect
      urethral continence mechanisms. MATERIALS AND METHODS: In female nulliparous
      Sprague-Dawley(r) rats under urethane anesthesia after ovariectomy with or
      without estrogen replacement we measured urethral response amplitude during
      sneezing, urethral baseline pressure and sneeze induced leak point pressure.
      Whole urethras were tested for ex vivo urethral properties. RESULTS: Urethral
      response amplitude during sneezing was significantly decreased in 3 and 6-week
      ovariectomized rats. Urethral baseline pressure was significantly decreased only
      in 6-week ovariectomized rats. After estrogen replacement urethral baseline
      pressure but not urethral response amplitude during sneezing was significantly
      increased. Neither 3-week ovariectomized nor sham operated rats leaked during
      sneezing but fluid leakage was observed in 63% of 6-week ovariectomized rats.
      Estrogen replacement decreased the stress urinary incontinence incidence to 25%.
      Ex vivo testing revealed a significant increase in middle urethral compliance and
      a decrease in beta stiffness at the proximal and middle urethras in 6-week
      ovariectomized rats. CONCLUSIONS: Results indicate that ovariectomy significantly
      impairs urethral function from the early stage (3 weeks) but does not induce
      stress urinary incontinence until the late stage (6 weeks). Also, estrogen
      replacement restores only the urethral baseline pressure parameter, leading to
      partial prevention of stress urinary incontinence. Since urethral baseline
      pressure and urethral response amplitude during sneezing parameters are related
      to urethral smooth and striated muscle activity, respectively, based on our
      previous studies, hormone replacement therapy may be partially effective for
      stress urinary incontinence by enhancing smooth muscle mediated urethral activity
      under stress conditions such as sneezing.

PMID- 21855913
TI  - 17alpha-Estradiol and genistein inhibit high fat diet induced prostate gene
      expression and prostate growth in the rat.
AB  - PURPOSE: High dietary fat and low phytoestrogen intake are associated with
      prostate cancer development and progression. Our previous study showed that
      exposure to a high fat diet significantly increased prostate 5alpha-reductase-2
      mRNA and prostate growth in the rat. In the current experiments we determined the
      effects of genistein and 17alpha-estradiol on the modulation of dietary fat
      induced prostate 5alpha-reductase-2 and insulin-like growth factor-1 gene
      expression, and prostate growth. MATERIALS AND METHODS: At weaning male ACI/Seg
      rats (Harlan(r) Sprague-Dawley(r)) were fed a low or a high fat diet, with or
      without genistein or 17alpha-estradiol for 2, 4 or 10 weeks. The prostate was
      dissected and weighed. We determined the levels of prostate 5alpha-reductase-2
      mRNA, insulin-like growth factor-1 mRNA, dihydrotestosterone, and plasma insulin
      like growth factor-1, dihydrotestosterone and testosterone. RESULTS: Two-week
      exposure to a high fat diet significantly increased prostate insulin-like growth
      factor-1 mRNA without significant changes in plasma insulin-like growth factor-1,
      which was blocked by genistein and 17alpha-estradiol. Genistein but not 17alpha
      estradiol also inhibited prostate 5alpha-reductase-2 mRNA and intraprostatic
      dihydrotestosterone induced by the high fat diet at 2 weeks. Genistein and
      17alpha-estradiol completely blocked high fat diet induced prostate growth at 10
      weeks of dietary treatment. However, neither genistein nor 17alpha-estradiol had
      any significant effect when co-administered with the low fat diet. CONCLUSIONS:
      Results indicate that genistein and 17alpha-estradiol can inhibit dietary fat
      induced changes in prostate 5alpha-reductase-2 and insulin-like growth factor-1
      gene expression, and prostate growth in the rat. This may be beneficial to
      prevent dietary fat associated prostate diseases such as prostate cancer.

PMID- 21855914
TI  - The usefulness of lumbosacral magnetic resonance imaging in the management of
      isolated dysfunctional elimination.
AB  - PURPOSE: Magnetic resonance imaging is sometimes used to rule out spinal
      pathology in patients with dysfunctional elimination, although its usefulness in
      this setting is unclear. We determined the usefulness of magnetic resonance
      imaging in children with isolated dysfunctional elimination, and normal
      cutaneous, neurological and orthopedic examinations. MATERIALS AND METHODS: We
      reviewed the records of children with dysfunctional elimination who underwent
      lumbosacral magnetic resonance imaging and identified those who were
      neurologically normal and who had normal cutaneous back examinations. Our primary
      goal was to determine the rate at which magnetic resonance imaging identified a
      spinal abnormality in this population. Univariate analysis was performed to
      assess the association of several clinical variables with a radiographic
      abnormality on magnetic resonance imaging. RESULTS: Between 2000 and 2009 a total
      of 49 lumbosacral magnetic resonance imaging studies were performed in 29 females
      and 18 males with a mean age of 8.5 years (range 2.1 to 17). Four of the 49
      imaging studies (8%) revealed a radiographic abnormality but in only 1 (2%) was
      clinically significant spinal pathology identified, that is filum lipoma causing
      cord tethering. Findings on the 3 remaining abnormal imaging studies were
      considered unrelated to bladder dysfunction. No clinical, demographic or
      videourodynamic findings were associated with a radiographic abnormality on
      magnetic resonance imaging. CONCLUSIONS: In children with isolated dysfunctional
      elimination complaints, and normal neurological, orthopedic and back examinations
      the diagnostic yield of lumbosacral magnetic resonance imaging is low but not
      zero. We suggest that spinal magnetic resonance imaging be used judiciously and
      as a test of last resort in these children.

PMID- 21855915
TI  - Expression patterns and roles of periostin during kidney and ureter development.
AB  - PURPOSE: Periostin is a secreted extracellular matrix protein that is
      differentially expressed in the developing kidney. We analyzed the temporal
      spatial expression of periostin in the developing kidney and ureter as well as
      its roles in ureter branching morphogenesis, nephrogenesis and ureter
      development. MATERIALS AND METHODS: RNA in situ hybridization and
      immunofluorescence histochemistry were used to investigate the expression of
      periostin, alphav integrin and alpha-smooth muscle actin during mouse renal and
      ureteral development. Metanephric explants were cultured in the presence of
      recombinant periostin, and ureteral branch points/tips and the glomerular number
      were quantified. Explants were also cultured in the presence of exogenous bone
      morphogenetic protein 4 and the effect on periostin mRNA levels was determined by
      quantitative real-time polymerase chain reaction. RESULTS: Periostin expression
      was observed in the mesenchyme surrounding the kidney and ureter, renal stroma,
      metanephric mesenchyme, ureter epithelium and developing nephrons. At embryonic
      day 15.5 periostin and alphav integrin, a common subunit of periostin receptors,
      were co-expressed in smooth muscle cells of the ureter, renal artery and
      intrarenal arteries. Bone morphogenetic protein 4 up-regulated periostin mRNA
      expression and exogenous periostin inhibited branching morphogenesis and
      glomerular number. CONCLUSIONS: Bone morphogenetic protein 4 which inhibits
      ureteral branching morphogenesis and promotes smooth muscle cell migration in the
      ureter up-regulated periostin mRNA expression in the developing kidney. Ureteral
      smooth muscle cells express periostin and alphav integrin. Periostin inhibited
      ureteral branching morphogenesis and glomerular number. Together these results
      suggest that periostin and bone morphogenetic protein 4 may have a role in
      branching morphogenesis, nephrogenesis and possibly smooth muscle cell migration.

PMID- 21855916
TI  - Re: Urinary pH is highly associated with tumor recurrence during intravesical
      mitomycin C therapy for nonmuscle invasive bladder tumor. T. Maeda, E. Kikuchi,
      K. Matsumoto, A. Miyajima and M. Oya. J Urol 2011; 185: 802-806.

PMID- 21855917
TI  - Lectin mediated biorecognition as a novel strategy for targeted delivery to
      bladder cancer.
AB  - PURPOSE: Inadequate urothelial delivery of drugs is considered a primary cause of
      current shortcomings in adjuvant intravesical chemotherapy for bladder cancer. We
      report what is to our knowledge a novel biorecognitive approach to achieve more
      regionally selective targeting of malignant tissue and improve urothelial uptake
      based on specific interaction between lectins and bladder cell glycocalyces.
      MATERIALS AND METHODS: We assessed the cytoadhesive and cytoinvasive potential of
      selected plant lectins in 3 human urothelial cell lines, corresponding to healthy
      tissue, and low and high grade carcinoma, respectively. Flow cytometry and
      fluorimetry were used to determine binding capacity and specificity in single
      cells and confluent monolayers. Monensin quenching experiments, microscopic
      analysis and enzyme treatment allowed further characterization of
      internalization, the uptake pathway and the potential cause of tumor selectivity.
      RESULTS: Wheat germ agglutinin had the highest bioadhesive potential while peanut
      agglutinin was the most potent discriminator between healthy and cancerous tissue
      (p <0.01). In each case cell interaction was highly specific (greater than 80%)
      and proved decisive for efficient uptake. Within 60 minutes after exposure
      greater than 50% of membrane bound lectins were internalized in acidic
      compartments. Cancer associated aberrant glycosylation likely represents the
      determining cause of peanut agglutinin selectivity. CONCLUSIONS: Given careful
      choice of the targeting ligand, the development of carbohydrate based delivery
      strategies for bladder cancer therapy seems feasible. Lectin bioadhesion may not
      only mediate preferential accumulation in malignant tissue but also promote
      cellular internalization via increased recruitment of membrane bound material to
      physiological uptake routes.

PMID- 21855918
TI  - Cremaster muscle myogenesis in the tip of the rat gubernaculum supports active
      gubernacular elongation during inguinoscrotal testicular descent.
AB  - PURPOSE: Cryptorchidism is a common abnormality and normal testicular descent is
      controlled by the gubernaculum. The cremaster may originate from abdominal
      muscles during gubernacular eversion or alternatively it may develop inside the
      gubernaculum. We studied cremaster myogenesis to determine how it develops.
      MATERIALS AND METHODS: Coronal sections of the pelvis were prepared from male
      Sprague-Dawley(r) rats and from males treated prenatally with the antiandrogen
      flutamide at embryonic day 19, and postnatal days 10, 19 and 35 after receiving
      ethical approval. Immunohistochemical stains were prepared for Ki67, Pax-7,
      myogenin, myosin heavy chain 7, Myh1, Myh2, Myh4, embryonic myosin, and slow and
      cardiac troponin T. Cell counts of the 1) gubernacular tip, 2) proximal
      gubernaculum/cremaster muscle and 3) adjacent abdominal wall are shown as a
      percent of positive fibers or positive cells per area. RESULTS: Throughout
      embryonic day 19, and postnatal days 10 and 19 proliferation (Ki67) was maximal
      at the gubernacular tip (p <0.001), as were muscle stem cells markers (Pax-7 p
      <0.05), early myogenesis (myogenin p <0.001) and immature muscle (Myh7, and slow
      and cardiac troponin T p <0.0001). In contrast, secondary (fast twitch, Myh1, 2
      and 4) fibers were more common in abdominal muscles (p <0.0001). Differences in
      muscle maturity and composition decreased with time. Flutamide treated rats
      showed more cellular proliferation than controls postnatally on postnatal day 10
      (p <0.001) as well as persistent immature embryonic myosin at the tip from
      postnatal day 19 (p <0.05). CONCLUSIONS: Results show that the rat cremaster
      muscle is more immature at the gubernacular tip, consistent with myogenesis
      occurring in the gubernaculum during migration to the scrotum, as proposed in
      humans.

PMID- 21855919
TI  - A murine model of inflammatory bladder disease: cathelicidin peptide induced
      bladder inflammation and treatment with sulfated polysaccharides.
AB  - PURPOSE: Studies show that LL-37 is a naturally occurring urinary defensin
      peptide that is up-regulated during urinary tract infections. Although normal
      urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may
      trigger bladder inflammation. We further suggest that anti-inflammatory sulfated
      polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can
      treat/prevent LL-37 mediated bladder inflammation. MATERIALS AND METHODS: C57BL/6
      mice were catheterized/instilled with LL-37 (320 MUM, 150 MUl) for 45 minutes.
      Animals were sacrificed at 12 and 24 hours, and tissues were examined using
      hematoxylin and eosin. Separate experiments were performed for myeloperoxidase to
      quantify inflammation. GM-1111 semi-synthetic glycosaminoglycan ether treatments
      involved instillation of 10 mg/ml for 45 minutes directly before or after LL-37.
      Tissues were harvested at 24 hours. To compare semi-synthetic glycosaminoglycan
      ether efficacy, experiments were performed using 10 mg/ml heparin. Finally,
      tissue localization of semi-synthetic glycosaminoglycan ether was examined using
      a fluorescent GM-1111-Alexa Fluor(r) 633 conjugate. RESULTS: Profound bladder
      inflammation developed after LL-37. Greater tissue inflammation occurred after 24
      hours compared to that at 12 hours. Myeloperoxidase assays revealed a 21 and 61
      fold increase at 12 and 24 hours, respectively. Semi-synthetic glycosaminoglycan
      ether treatment after LL-37 showed mild attenuation of inflammation with
      myeloperoxidase 2.5-fold below that of untreated bladders. Semi-synthetic
      glycosaminoglycan ether treatment before LL-37 demonstrated almost complete
      attenuation of inflammation. Myeloperoxidase results mirrored those in controls.
      In heparin treated bladders minimal attenuation of inflammation occurred.
      Finally, instillation of GM-1111-Alexa Fluor 633 revealed urothelial coating,
      significant tissue penetration and binding to endovasculature. CONCLUSIONS: We
      developed what is to our knowledge a new model of inflammatory bladder disease by
      challenge with the naturally occurring urinary peptide LL-37. We also noted that
      a new class of anti-inflammatory sulfated polysaccharides prevents and mitigates
      bladder inflammation.

PMID- 21855920
TI  - Hydronephrosis in children with abdominal and pelvic neoplasms: outcome and
      survival analysis of a single center pediatric oncology series.
AB  - PURPOSE: We ascertained the incidence and outcome of hydronephrosis related to
      abdominal or pelvic neoplasms and survival in pediatric patients. MATERIALS AND
      METHODS: We retrospectively reviewed our institutional oncology database between
      January 1995 and November 2009. We reviewed the charts of all children with intra
      abdominal (nonrenal) and pelvic neoplasms. RESULTS: Of the 366 patients whose
      charts were reviewed 66 (18%) had hydronephrosis at some point during treatment,
      including 12 with hydronephrosis that was not caused by the neoplasm and 1 who
      was lost to followup, leaving 53 with malignant obstruction. Of the remaining
      patients hydronephrosis resolved in 34 (64%) with treatment for the primary
      neoplasm alone while in 19 (36%) hydronephrosis persisted after primary
      oncological treatment. Univariate analysis revealed that patients with persistent
      hydronephrosis (p = 0.025), those with urological intervention (p = 0.05) and
      those with high stage disease (p <0.001) had statistically significantly worse
      overall survival. On Cox multivariate analysis only disease stage remained
      statistically significant (p = 0.004). CONCLUSIONS: Analysis of this group
      revealed that pediatric nonrenal abdominal and pelvic tumors are associated with
      hydronephrosis in about 20% of cases. Approximately 60% of these cases resolved
      with treatment for the primary tumor alone while 13% required specific urological
      intervention for urinary tract involvement or compression. Patients with
      pediatric malignant ureteral obstruction had a 20% 5-year mortality rate. The
      main predictive factor was primary disease stage.

PMID- 21855921
TI  - Impact of anatomical and socioeconomic factors on timing of urological
      consultation for boys with cryptorchidism.
AB  - PURPOSE: Cryptorchidism is a common finding in infants and young boys. Early
      repair lessens the extent of testicular injury. We hypothesized that anatomical
      and socioeconomic factors affect the timing of consultation and treatment for
      boys with cryptorchidism. MATERIALS AND METHODS: Under an institutional review
      board approved protocol we reviewed the records at a single institution of
      children who underwent exploration for unilateral or bilateral cryptorchidism.
      Demographic and anatomical factors were recorded. RESULTS: The median age of 677
      boys at consultation and surgery was 20.3 and 28.9 months, respectively. Median
      age at consultation for boys with nonpalpable and palpable testicles was 12.3 and
      20.9 months, respectively (p = 0.03). Boys with a concomitant penile anomaly had
      a younger median age at consultation than boys without a penile anomaly (8.5 vs
      20.3 months, p <0.01). Demographic factors did not vary with respect to time to
      consultation and surgery (p >0.05). Multivariate analysis showed that abdominal
      site and concomitant penile anomaly were associated with earlier time to
      consultation (p = 0.02 and <0.01, respectively). CONCLUSIONS: The timing of
      consultation for boys with undescended testicles does not vary in regard to race,
      language or insurance type at this tertiary care institution. Instead, anatomical
      factors influenced age at consultation for boys with cryptorchidism. This
      suggests that in some geographic regions access to care is not restricted for
      minorities or noncommercially insured children.

PMID- 21855922
TI  - Voiding cystourethrogram--are our protocols the same?
AB  - PURPOSE: Voiding cystourethrogram is the gold standard for evaluating and
      diagnosing vesicoureteral reflux. Reflux detection can potentially be affected by
      many parameters during voiding cystourethrogram. MATERIALS AND METHODS: A 29-item
      survey was sent via e-mail through SurveyMonkey(r) to the chairperson of
      pediatric radiology at 65 national pediatric hospitals. This survey included
      questions on institutional protocols for performing voiding cystourethrogram.
      RESULTS: Responses were received from 41 institutions from across North America,
      including 17 of 19 Randomized Intervention for Children with Vesicoureteral
      Reflux study sites. Many aspects of the reports of voiding cystourethrogram
      protocols were similar with 90% or greater agreement in allowing parents in the
      room, contrast infusion by gravity, catheter or feeding tube use without
      balloons, no contrast dilution and voiding without a catheter in place. The
      height at which contrast medium was raised for infusion was 40, 60, 80, 100 and
      greater than 100 cm at 2.4%, 17.1%, 17.1%, 39.0% and 12.2% of sites,
      respectively, while the height was not measured or it varied at 12.2%. The
      infilling phase stopped when the bladder appeared full at 2.4% of sites, infusion
      stopped itself at 12.2%, patient voided at 61.0%, volume attained age expected
      capacity at 12.2%, the patient was uncomfortable at 4.9% and results varied at
      7.3%. CONCLUSIONS: Data reveal that voiding cystourethrogram is performed
      differently across North America and no standard protocol exists for the
      procedure. These differences could significantly impact voiding cystourethrogram
      results among institutions and taint our ability to compare results in the
      literature.

PMID- 21855924
TI  - Ventriculoperitoneal shunt infections after bladder surgery: is mechanical bowel
      preparation necessary?
AB  - PURPOSE: We investigated whether children with a ventriculoperitoneal shunt who
      undergo mechanical bowel preparation before bladder reconstruction with bowel
      have a lower rate of infection than children who do not undergo preoperative
      bowel preparation. MATERIALS AND METHODS: We performed an institutional review
      board approved, retrospective chart review of the incidence of
      ventriculoperitoneal shunt infections after bladder reconstruction using bowel
      and compared infection rates using Fisher's exact test. Mean +/- SD followup was
      2.9 +/- 2.3 years. RESULTS: Between 2003 and 2009, 31 patients with a
      ventriculoperitoneal shunt underwent bladder reconstruction using bowel, of whom
      19 (61%) and 12 (39%) did and did not undergo mechanical bowel preparation,
      respectively. There was no significant difference in gender or age at surgery
      between the 2 groups. Infection developed in 3 children (9.6%) within 2 months
      postoperatively, including 2 (10.5%) with and 1 (8.3%) without bowel preparation
      (2-tailed p = 1.0). CONCLUSIONS: There was no significant difference in the shunt
      infection rate between patients with a ventriculoperitoneal shunt who did and did
      not undergo preoperative bowel preparation. Our results add to the current
      literature suggesting that bowel preparation is unnecessary even in patients with
      a ventriculoperitoneal shunt.

PMID- 21855923
TI  - Sacral nerve stimulator revision due to somatic growth.
AB  - PURPOSE: Sacral nerve modulation is a Food and Drug Administration approved
      treatment for refractory urgency, frequency, urge incontinence and nonobstructive
      urinary retention in adults. The sparse literature on sacral nerve modulation in
      children focuses on its initial efficacy in patients with neurogenic bladder and
      dysfunctional elimination. We describe our initial experience with sacral nerve
      modulation and the phenomenon of growth spurts associated with lead malfunction
      that necessitates revision. MATERIALS AND METHODS: After receiving institutional
      review board approval we retrospectively reviewed the charts of pediatric
      patients who underwent sacral nerve modulation surgery at our institution. Charts
      were examined for patient demographics, subjective success, the need for further
      surgery and success after revision. RESULTS: Four patients underwent sacral nerve
      modulation at an average age of 12.1 years. All patients reported initial
      success, defined as greater than 50% symptom improvement. Subsequently 3 patients
      required a total of 5 revisions due to lead malfunction with an average of 1.5
      years between surgeries. In those requiring revision the average somatic growth
      between revisions was 8.1 cm. Return of efficacy was reported after each
      revision. All patients had functioning nerve stimulators in place and continued
      to have a positive subjective response. CONCLUSIONS: The sparse data on sacral
      nerve modulation in children shows efficacy and safety similar to those in
      adults. Somatic growth may be associated with lead malfunction and require
      surgical revision. We report a small series showing that revision can be done
      successfully and safely. Informed consent for sacral nerve modulation in
      pediatric patients should include a discussion of somatic growth as a possible
      cause of lead malfunction necessitating revision.

PMID- 21855925
TI  - Stephen A. Koff.

PMID- 21855926
TI  - Idiopathic granulomatous orchitis.

PMID- 21855927
TI  - Decreased urethral mucosal damage and delayed bacterial colonization during short
      term urethral catheterization using a novel trefoil urethral catheter profile in
      rabbits.
AB  - PURPOSE: We evaluated the efficacy of a novel catheter with a trefoil profile to
      decrease urothelial irritation and delay catheter associated urinary tract
      infections by comparing it with a conventional catheter in the rabbit model.
      MATERIALS AND METHODS: A novel catheter was made of medical silicone with a
      trefoil profile design. A total of 66 male New Zealand White rabbits were
      anesthetized and equally randomized into a control or a novel trefoil profile
      catheter group. Of the animals 10 per group were sacrificed at days 2, 4 and 8 of
      catheterization, respectively. Urine samples were cultured and urethral tissues
      were histopathologically evaluated. The remaining 6 rabbits were selected for
      urethral endoscopic assessment at day 10. RESULTS: After 4 days of
      catheterization the novel trefoil catheter profile decreased the rate of
      bacteriuria, defined as less than 100 cfu/ml, in 3 rabbits with a novel catheter
      vs that in 8 with a control catheter (p <0.05). Histopathological assessment
      revealed minor differences in staining in the short term. Endoscopic assessment
      showed more obvious mucosal inflammatory changes in 2 of the 3 controls than in
      the 3 rabbits with a novel catheter. CONCLUSIONS: Results demonstrate that the
      novel catheter harbors a property of decreasing urothelial irritation and
      delaying catheter associated urinary tract infection. This advantage over
      conventional catheters makes it a potential alternative for short-term
      catheterization. Clinical trials are forthcoming.

PMID- 21855928
TI  - The impact of the alexander technique on improving posture and surgical
      ergonomics during minimally invasive surgery: pilot study.
AB  - PURPOSE: One of the main ergonomic challenges during surgical procedures is
      surgeon posture. There have been reports of a high number of work related
      injuries in laparoscopic surgeons. The Alexander technique is a process of
      psychophysical reeducation of the body to improve postural balance and
      coordination, permitting movement with minimal strain and maximum ease. We
      evaluated the efficacy of the Alexander technique in improving posture and
      surgical ergonomics during minimally invasive surgery. MATERIALS AND METHODS: We
      performed a prospective cohort study in which subjects served as their own
      controls. Informed consent was obtained. Before Alexander technique
      instruction/intervention subjects underwent assessment of postural coordination
      and basic laparoscopic skills. All subjects were educated about the Alexander
      technique and underwent post-instruction/intervention assessment of posture and
      laparoscopic skills. Subjective and objective data obtained before and after
      instruction/intervention were tabulated and analyzed for statistical
      significance. RESULTS: All 7 subjects completed the study. Subjects showed
      improved ergonomics and improved ability to complete FLSTM as well as subjective
      improvement in overall posture. CONCLUSIONS: The Alexander technique training
      program resulted in a significant improvement in posture. Improved surgical
      ergonomics, endurance and posture decrease surgical fatigue and the incidence of
      repetitive stress injuries to laparoscopic surgeons. Further studies of the
      influence of the Alexander technique on surgical posture, minimally invasive
      surgery ergonomics and open surgical techniques are warranted to explore and
      validate the benefits for surgeons.

PMID- 21855929
TI  - Age at cryptorchidism diagnosis and orchiopexy in Denmark: a population based
      study of 508,964 boys born from 1995 to 2009.
AB  - PURPOSE: Early treatment for cryptorchidism may be necessary to preserve
      fertility. International guidelines now recommend that congenital cryptorchidism
      be treated with orchiopexy before age 1 year. Acquired cryptorchidism should be
      treated at presentation. To our knowledge the rate of adherence to these
      guidelines in recent years is unknown. Thus, we present data on age at
      cryptorchidism diagnosis and orchiopexy in recent Danish birth cohorts. MATERIALS
      AND METHODS: A population of 508,964 Danish boys born alive from January 1, 1995
      to December 31, 2009 was identified using the Danish Civil Registration System.
      Five birth cohorts were defined, including 1995 to 1997, 1998 to 2000, 2001 to
      2003, 2004 to 2006 and 2007 to 2009. The boys were followed in the Danish
      National Patient Registry for a diagnosis of cryptorchidism and for an orchiopexy
      procedure. Data were analyzed using the Kaplan-Meier estimator and Cox regression
      models. RESULTS: During followup 10,094 boys were diagnosed with cryptorchidism,
      of whom 5,473 underwent orchiopexy. Mean age at diagnosis in boys followed at
      least 6 years was 3.3 years (95% CI 3.3-3.4) in the 1995 to 1997 cohort, 3.1 (95%
      CI 3.1-3.2) in the 1998 to 2000 cohort and 2.9 (95% CI 2.8-2.9) in the 2001 to
      2003 cohort while mean age at orchiopexy was 3.8 (3.7-3.9), 3.6 (3.5-3.7) and 3.3
      years (3.2-3.4), respectively. CONCLUSIONS: In the more recent birth cohorts of
      1995 to 2009 we observed a shift toward younger age at cryptorchidism diagnosis
      and orchiopexy.

PMID- 21855930
TI  - Analysis of the clinical significance and cost associated with the routine
      pathological analysis of pediatric inguinal hernia sacs.
AB  - PURPOSE: Pediatric inguinal and scrotal surgeries for inguinal hernia,
      cryptorchidism and hydrocele are common and usually involve the excision of a
      hernia sac. Groups at many centers send hernia sacs for pathological analysis to
      identify occult disease as well as structures that may have been erroneously
      resected. We hypothesized that, since the incidence of significant findings is
      low and the associated health care costs are significant, the routine
      pathological analysis of inguinal hernia sacs is unnecessary. MATERIALS AND
      METHODS: After receiving institutional review board approval we retrospectively
      reviewed pathology reports at our institution of patients who underwent surgery
      with an inguinal hernia sac sent for pathological analysis from January 2000 to
      September 2009. The primary outcome was to determine the incidence of clinically
      significant structures in hernia sac specimens. The secondary outcome was to
      evaluate the costs associated with analyzing these specimens. RESULTS: A total of
      2,287 boys and 441 girls underwent some form of inguinal or scrotal surgery
      during the study. In the 2,287 boys a total of 2,657 hernia sac specimens were
      analyzed, of which 2 (0.08%) contained clusters of epididymal-like tubules. Most
      unexpected findings were likely clinically insignificant, including mesothelial
      proliferation in 5.6% of cases, genital duct remnants in 0.8%, lipoma in 0.23%
      and adrenocortical rests in 0.04%. The average cost of analyzing hernia sac
      specimens at our institution was approximately $7,100 Canadian annually.
      CONCLUSIONS: Routine analysis of inguinal hernia sacs is unnecessary and costly,
      and should be reserved for cases in which resection of important structures such
      as the vas deferens is suspected.

PMID- 21855931
TI  - In vitro analysis of the bactericidal activity of Escherichia coli Nissle 1917
      against pediatric uropathogens.
AB  - PURPOSE: The usefulness of prophylactic antibiotics to prevent recurrent urinary
      tract infections in children was recently questioned. Some groups have attempted
      to use probiotics, most commonly lactobacillus, to prevent recurrent infections
      by altering the intestinal bacterial reservoir with variable results. Mutaflor(r)
      is a possible alternative probiotic in which the active agent is Nissle 1917.
      Nissle 1917 is a commensal Escherichia coli strain that eradicates pathogenic
      bacteria from the gastrointestinal tract. Due to its ability to alter the
      intestinal biome we hypothesized that Mutaflor may have the potential to prevent
      recurrent urinary tract infections. Thus, we used an in vitro assay to analyze
      the effectiveness of Nissle 1917 for eradicating pediatric uropathogens.
      MATERIALS AND METHODS: We established a collection of 43 bacterial pediatric
      uropathogens. With each isolate a microcin-type assay was performed to determine
      the effectiveness of Nissle 1917 on bacterial growth inhibition and competitive
      overgrowth. RESULTS: Nissle 1917 adversely affected the growth of 34 of the 43
      isolates (79%) isolates. It inhibited the growth of 21 isolates and overgrew 13.
      The percent of species adversely affected by Nissle 1917 was 40% for Pseudomonas,
      50% for E. coli, Enterococcus and Staphylococcus, 100% for Klebsiella and
      Enterobacter, and 0% for Citrobacter and Serratia. CONCLUSIONS: Nissle 1917, the
      active agent in Mutaflor, inhibited or out competed most bacterial isolates.
      These mechanisms could be used in vivo to eradicate uropathogens from the
      gastrointestinal tract. Further study is needed to determine whether Mutaflor can
      prevent recurrent urinary tract infections in children.

PMID- 21855932
TI  - Physiological changes in transperitoneal versus retroperitoneal laparoscopy in
      children: a prospective analysis.
AB  - PURPOSE: The choice of minimally invasive surgical approaches in pediatric
      urology is largely influenced by surgeon preference and experience. Little is
      known about the differences in physiological variables that might objectively
      influence the choice of surgical approach. We compared the cerebral and systemic
      hemodynamic effects of transperitoneal vs retroperitoneal CO(2) insufflation in
      children. MATERIALS AND METHODS: After receiving ethical review board approval
      and written parental consent 36 pediatric patients undergoing transperitoneal
      (18) or retroperitoneal (18) laparoscopic surgery were enrolled in this study. A
      standardized anesthetic technique of isoflurane 1 MAC and remifentanil 0.2 mcg/kg
      per minute was used. Measured parameters included end tidal CO(2), middle
      cerebral artery blood flow velocity, heart rate and noninvasive mean arterial
      blood pressure. Transcranial Doppler ultrasound was used to measure middle
      cerebral artery blood flow velocity. Data were collected before, during and after
      CO(2) insufflation to 12 mm Hg pneumoperitoneum at regular intervals, including
      every minute for 10 minutes and every 2 minutes thereafter. Within group analysis
      was done using repeated measures ANOVA. Nonlinear regression analysis was used to
      determine the best fit and the relationship of each variable with time with p
      <0.05 considered significant. RESULTS: Patient age and weight were comparable in
      the 2 groups. Transperitoneal CO(2) insufflation resulted in a rapid parallel
      increase in middle cerebral artery blood flow velocity, mean arterial pressure
      and end tidal CO(2) during the first 8 minutes of pneumoperitoneum (p <0.05).
      Despite a continued increase in end tidal CO(2) thereafter middle cerebral artery
      blood flow velocity and mean arterial pressure attained a plateau within the
      first 8 minutes (p <0.05). In contrast, middle cerebral artery blood flow
      velocity and end tidal CO(2) increased progressively throughout the
      retroperitoneal CO(2) insufflation period (p <0.01). CONCLUSIONS: Cerebral blood
      flow velocity and end tidal CO(2) seem to increase progressively and gradually
      during retroperitoneal laparoscopy, in contrast to the more rapid increase and
      plateau effect during transperitoneal laparoscopy. Presumably the smaller
      absorptive surface in the retroperitoneal space explains this physiological
      difference.

PMID- 21855933
TI  - Interleukin-18 stimulates a positive feedback loop during renal obstruction via
      interleukin-18 receptor.
AB  - PURPOSE: Interleukin-18 is a proinflammatory cytokine that is an important
      mediator of obstruction induced renal tubulointerstitial fibrosis independent of
      tumor necrosis factor-alpha and beta1 activity. We hypothesized that interleukin
      18 stimulates a positive feedback loop during obstruction via interleukin-18
      receptor to increase interleukin-18 gene expression and protein production.
      MATERIALS AND METHODS: Male C57BL6 interleukin-18 receptor knockout (The Jackson
      Laboratory, Bar Harbor, Maine) and control wild-type mice underwent unilateral
      ureteral obstruction or sham operation and were sacrificed 1 week after surgery.
      Renal cortical tissue samples were harvested and analyzed for interleukin-18
      protein by enzyme-linked immunosorbent assay, and for interleukin-18 and
      interleukin-18 receptor gene expression by quantitative polymerase chain
      reaction. The specific cellular localization of interleukin-18 and interleukin-18
      receptor expression during obstruction was assessed using dual labeling
      immunofluorescence staining. RESULTS: Renal interleukin-18 receptor expression
      increased significantly in wild-type mice in response to obstruction but remained
      at sham operation levels in interleukin-18 receptor knockout mice. Similarly
      while interleukin-18 protein and gene expression were significantly increased in
      wild-type mice in response to obstruction, interleukin-18 levels and gene
      expression were significantly decreased during obstruction in knockout mice.
      Obstruction induced interleukin-18 and interleukin-18 receptor production were
      localized predominantly to tubular epithelial cells and to a lesser extent to the
      renal interstitium. CONCLUSIONS: Results reveal that interleukin-18 stimulates a
      positive feedback loop via interleukin-18 receptor during renal obstruction to
      stimulate interleukin-18 production and gene expression. The predominant cellular
      source of interleukin-18 production during renal obstruction appears to be
      tubular epithelial cells rather than infiltrating macrophages.

PMID- 21855934
TI  - Up-regulation of alpha1a and alpha1d-adrenoceptors in the prostate by
      administration of subtype selective alpha1-adrenoceptor antagonist tamsulosin in
      patients with benign prostatic hyperplasia.
AB  - PURPOSE: We examined the change in alpha(1)-adrenoceptor subtype expression in
      the prostate due to chronic tamsulosin administration in a benign prostatic
      hyperplasia rat model and in patients. MATERIALS AND METHODS: We measured
      alpha(1)-adrenoceptor subtype expression after tamsulosin administration in the
      prostate of the benign prostatic hyperplasia rat model using TaqMan(r) reverse
      transcriptase-polymerase chain reaction. We also measured expression before and
      after 12-week tamsulosin treatment in the prostate of patients with benign
      prostatic hyperplasia. We examined the correlation between the change in alpha(1)
      adrenoceptor expression due to tamsulosin treatment and acute urinary retention
      during long-term followup. RESULTS: The expression of alpha(1a) and alpha(1d)
      adrenoceptors was significantly increased in dose dependent fashion by tamsulosin
      in the benign prostatic hyperplasia rat model. Median mRNA expression of subtypes
      alpha(1a) and alpha(1d)-adrenoceptors was 1.4 (IQR 0.6, 3.0) and 1.7 * 1,000
      copies per 1 ng beta-actin (IQR 0.9, 2.4) before treatment, and 6.0 (IQR 2.0,
      8.0) and 2.2 * 1,000 copies per 1 ng beta-actin (IQR 1.7, 3.6), respectively,
      after treatment. The expression of alpha(1a) and alpha(1d)-adrenoceptors
      significantly increased after tamsulosin treatment (p <0.01 and <0.05,
      respectively). This increase was observed in 10 patients in whom acute urinary
      retention did not develop during long-term followup but not in 4 in whom acute
      urinary tract retention developed. CONCLUSIONS: Tamsulosin up-regulated alpha(1a)
      and alpha(1d)-adrenoceptors, suggesting that it has clinical selectivity for
      alpha(1a) and alpha(1d)-adrenoceptors. Up-regulation of alpha(1)-adrenoceptors
      subtype expression is considered an adaptive response to chronic tamsulosin
      administration. The difference in the response to alpha(1)-adrenoceptors
      antagonists among patients may contribute to the diversity in the long-term
      efficiency of alpha(1)-adrenoceptor antagonists.

PMID- 21855935
TI  - A novel Y chromosome microdeletion with the loss of an endogenous retrovirus
      related, testis specific transcript in AZFb region.
AB  - PURPOSE: We identified the endogenous retroviruses associated with TTYs (testis
      specific transcripts linked to the Y) in the AZFb region. We evaluated the
      relationship between endogenous retroviruses, and TTY expression patterns and
      function in spermatogenesis. MATERIALS AND METHODS: We identified family members
      of TTYs in the AZFb region using computational screening. After investigating the
      relationship between the endogenous retrovirus genome and TTY expression patterns
      we screened genomic polymerase chain reaction products from TTY13 amplified from
      790 Japanese men, including 275 with azoospermia, 285 with oligozoospermia and
      230 who were fertile. RESULTS: Computational screening revealed that 3 members of
      the TTY family, TTY9, 10 and 13, were regulated by endogenous retroviruses in the
      AZFb region. Homologous recombination between long terminal repeat of the TTY13
      associated human endogenous retrovirus-K14C resulted in TTY13 deletion events.
      These deletions were more common in patients with azoospermia and oligozoospermia
      than in fertile males. Specifically 15.63% of the azoospermia group, 10.88% of
      the oligozoospermia group and 0% of fertile controls had only the deletion
      variant, indicating an association between the homologous recombination rate and
      the severity of spermatogenesis failure that was statistically significant (p
      <0.05). CONCLUSIONS: Because of the finding of what are to our knowledge novel
      microdeletions due to endogenous retrovirus in the AZFb region, our study raises
      the possibility that specific variations in genomic structure may contribute to
      some forms of human idiopathic male infertility.

PMID- 21855936
TI  - Laparoscopic management of multiple ureteral polyps in children.
AB  - PURPOSE: We describe laparoscopic management of multiple ureteral polyps and our
      objective initial experience in children. MATERIALS AND METHODS: We used
      laparoscopic polypectomy and pyeloureterostomy to treat 13 patients (15 ureters)
      diagnosed with hydronephrosis caused by multiple ureteral polyps between August
      2006 and November 2010. Mean patient age was 11.4 years. The polyps were left
      sided in 9 patients, right sided in 2 and bilateral in 2. Hydronephrosis was mild
      in 9 cases, moderate in 4 and severe in 2. Postoperative followup consisted of
      ultrasound and excretory urography. RESULTS: A total of 12 patients were
      successfully treated with laparoscopy, while 1 patient with bilateral polyps
      required conversion to open surgery. Mean polyp length was 4.5 cm. Mean operative
      time in the unilateral cases was 121 minutes. The bilateral polyps were operated
      on simultaneously, with a surgical time of 185 minutes. Mean hospital stay was
      3.5 days. Followup ranged from 6 to 26 months. In 1 patient obstruction of the
      temporary Double-J(r) stent developed 1 week postoperatively due to the
      deposition of urinary salts. No recurrent polyps were seen on followup B-mode
      ultrasound or excretory urography. CONCLUSIONS: Laparoscopic management of
      multiple ureteral polyps in children can be considered a safe and effective
      minimally invasive surgical option. However, further studies with larger cohorts
      are needed to confirm this finding.

PMID- 21855937
TI  - Degree of urge, perception of bladder fullness and bladder volume--how are they
      related?
AB  - PURPOSE: We evaluated the reliability of the degree of urge and perception of
      bladder fullness scales, the relationship between the scales and bladder volume,
      and possible differences between bladder sensations experienced in a controlled
      or an uncontrolled setting. MATERIALS AND METHODS: Volunteers and patients with
      overactive bladder symptoms participated in the protocols. They were asked to
      grade bladder sensation on a 4-point urge scale of no sensation to need to void
      now and assess the perception of fullness on a visual analog scale of empty to
      full bladder. This was assessed in a 3-day bladder diary and during controlled,
      noninvasive bladder filling. RESULTS: Each scale was reliable and significantly
      related to bladder volume (p <0.001). Agreement between the scales and voided
      volume was poor. Patients and volunteers grade bladder fullness and degree of
      urge higher in an uncontrolled than in a controlled setting. CONCLUSIONS: The
      perception of bladder fullness and the degree of urge have a significant relation
      to bladder volume in controlled and uncontrolled settings. Due to poor agreement
      between the scales and actual voided volume these scales cannot replace measuring
      voided volume. The perception of bladder sensation depends on the setting.
      Bladder sensation at the hospital might underestimate the bother of symptoms
      experienced by a patient in daily life.

PMID- 21855938
TI  - Urological disorders in chronic kidney disease in children cohort: clinical
      characteristics and estimation of glomerular filtration rate.
AB  - PURPOSE: Urological disorders are the most common cause of pediatric chronic
      kidney disease. We determined the characteristics of children with urological
      disorders and assessed the agreement between the newly developed bedside
      glomerular filtration rate estimating formula with measured glomerular filtration
      rate in 586 patients in the Chronic Kidney Disease in Children study. MATERIALS
      AND METHODS: The Chronic Kidney Disease in Children study is a prospective,
      observational cohort of children recruited from 48 sites in the United States and
      Canada. Eligibility requirements include age 1 to 16 years and estimated
      glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73
      m(2). Baseline demographics, clinical variables and glomerular filtration rate
      were assessed. Bland-Altman analysis was conducted to assess agreement between
      estimated and measured glomerular filtration rates. RESULTS: Of the 586
      participants with at least 1 glomerular filtration rate measurement 348 (59%) had
      an underlying urological diagnosis (obstructive uropathy in 118,
      aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition
      in 39). Among these patients median age was 9 years, duration of chronic kidney
      disease was 7 years and age at first visit with a urologist was less than 1 year.
      Of the patients 67% were male, 67% were white and 21% had a low birth weight.
      Median height was in the 24th percentile. Median glomerular filtration rate as
      measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median
      glomerular filtration rate as estimated by the Chronic Kidney Disease in Children
      bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p =
      0.44). CONCLUSIONS: Underlying urological causes of chronic kidney disease were
      present in 59% of study participants. These children were diagnosed early in
      life, and many had low birth weight and growth delay. There is good agreement
      between the newly developed Chronic Kidney Disease in Children estimating
      equations and measured glomerular filtration rate in this population.

PMID- 21855939
TI  - Screening for malignancy after augmentation cystoplasty in children with spina
      bifida: a decision analysis.
AB  - PURPOSE: Augmentation cystoplasty is the mainstay of surgical treatment for
      medically refractory neurogenic bladder in patients with spina bifida. Concerns
      regarding an increased risk of malignancy have prompted many centers to consider
      routine postoperative screening. We examine the potential cost-effectiveness of
      such screening. MATERIALS AND METHODS: A Markov model was used to compare 2
      screening strategies among patients with spina bifida after cystoplasty, namely
      annual screening cystoscopy and cytology and usual care. Model parameters were
      informed via a systematic review of post-augmentation malignancy and cost
      estimates from published reports or government sources. RESULTS: In a
      hypothetical cohort the individual increase in life expectancy for the entire
      cohort was 2.3 months with an average lifetime cost of $55,200 per capita, for an
      incremental cost-effectiveness ratio of $273,718 per life-year gained. One-way
      and two-way sensitivity analyses suggest the screening strategy could be cost
      effective if the annual rate of cancer development were more than 0.26% (12.8%
      lifetime risk) or there were a greater than 50% increase in screening
      effectiveness and cancer risk after augmentation. After adjusting for multiple
      levels of uncertainty the screening strategy had only an 11% chance of being cost
      effective at a $100,000 per life-year threshold or a less than 3% chance of being
      cost effective at $100,000 per quality adjusted life-year. CONCLUSIONS: Annual
      screening for malignancy among patients with spina bifida with cystoplasty using
      cystoscopy and cytology is unlikely to be cost effective at commonly accepted
      willingness to pay thresholds. This conclusion is sensitive to a higher than
      expected risk of malignancy and to highly optimistic estimates of screening
      effectiveness.

PMID- 21855940
TI  - Urinary retention after orthotopic neobladder substitution in females.
AB  - PURPOSE: Urinary retention is a common complication after orthotopic neobladder
      urinary diversion. We reviewed a case series of women who underwent neobladder
      creation and discuss anatomical findings, and urinary retention etiology and
      prevention. MATERIALS AND METHODS: We retrospectively reviewed the records of all
      orthotopic neobladder urinary diversions in female patients performed at our
      institution from 1999 through 2010. We abstracted baseline clinical and
      demographic characteristics, operative information, and postoperative clinical,
      urodynamic, imaging and secondary procedure followup. We defined urinary
      retention as the need for intermittent catheterization. RESULTS: We identified 21
      female patients who underwent neobladder diversion. Median age at cystectomy was
      62 years (range 43 to 77). Median followup was 3 years (range 3 to 138 months).
      Of the patients 14 underwent ileocolic diversion, 6 underwent Studer ileal
      diversion and 1 underwent preservation of a right colon augmentation. All
      patients underwent prior or concurrent hysterectomy. In 2 patients with a history
      of genitourinary tuberculosis neobladder-vaginal fistulas developed
      postoperatively and they were excluded from analysis. Of the 19 female patients
      with a neobladder included in analysis 7 (36.8%) experienced urinary retention
      requiring clean intermittent catheterization. Associated abnormalities included
      neocystocele formation in 6 cases, anastomotic stricture in 1 and progressive
      neurological disease in 1. Upon straining the average neobladder descent was
      approximately 2 cm and the average change in the neocystourethral angle in
      patients with neocystoceles was 18 degrees. Of the patients 11 (57.9%) had a
      nonobstructive voiding pattern. CONCLUSIONS: Urinary retention in female patients
      with a neobladder can be functional, anatomical or multifactorial. In our series
      common anatomical findings associated with urinary retention were neocystocele
      formation and urethral kinking.

PMID- 21855941
TI  - Treatment of post-prostatectomy incontinence with male slings in patients with
      impaired detrusor contractility on urodynamics and/or who perform Valsalva
      voiding.
AB  - PURPOSE: Male slings have emerged as a popular and efficacious treatment for men
      with post-prostatectomy stress urinary incontinence. Traditionally slings have
      been used with caution or avoided in men with impaired detrusor contractility or
      Valsalva voiding because of concern that patients will not be able to overcome
      the fixed resistance of a sling during micturition. We propose that men with post
      prostatectomy urinary incontinence who have impaired contractility and/or void
      with abdominal straining for urodynamics can be safely treated with slings.
      MATERIALS AND METHODS: A retrospective review of patients with post-prostatectomy
      urinary incontinence who underwent an initial sling procedure between January
      2004 and January 2010 was conducted at a single institution. Preoperative
      urodynamic characteristics, and postoperative Patient Global Impression of
      Improvement, post-void residual and noninvasive uroflow data were examined.
      Patients were grouped by poor bladder contractility or Valsalva voiding status.
      Exclusion criteria were lack of preoperative urodynamics and/or postoperative
      post-void residual. A total of 92 patients were analyzed. The variables were
      compared using the Student t test and the chi-square test. RESULTS: No
      statistically significant difference was shown in postoperative post-void
      residual (mean 4 months postoperatively) or urinary retention when comparing by
      bladder contractility or Valsalva voiding. In the subset of patients with
      available postoperative uroflow data, there were no differences in postoperative
      maximum flow rate or voided volume. CONCLUSIONS: Men with post-prostatectomy
      urinary incontinence with urodynamic findings suggesting impaired contractility
      or Valsalva voiding can be safely treated with sling surgery if they have normal
      preoperative emptying.

PMID- 21855942
TI  - Northwestern University pilot urology residency curriculum: impact of flexible
      training and residency electives on educational outcomes.
AB  - PURPOSE: We report on our first 4 years of experience with a pilot urology
      residency curriculum. This novel program was approved by the Urology Residency
      Review Committee and involves a flexible educational program for residents,
      incorporating elective time (4 months each in postgraduate years 2 and 4 of
      training) into the residency rotation schedule. MATERIALS AND METHODS: We
      performed a prospective assessment of the urology residency program overall, the
      electives chosen by the residents, and the impact on resident operative logs and
      in-service scores compared to residents completing residency before the
      implementation of the elective curriculum. Overall faculty and resident
      evaluation of the residency program and elective curriculum was collected, and
      categorized as positive, negative or neutral. RESULTS: When comparing the first 3
      years of the pilot program to the 5 years before implementation of the program,
      the average final graduated resident case total increased by 232 (2,390 vs
      2,158). Resident in-service scores (postgraduate years 3 to 5) trended higher
      since the elective program was instituted with a 5% increase in percentile scores
      compared to their peers (75% vs 72%). Subjective evaluations of the new residency
      program by residents and faculty were overwhelmingly positive. CONCLUSIONS: The
      pilot urology residency curriculum including elective time had a positive impact
      on the program based on resident and faculty feedback without a deleterious
      effect on urology index case logs or in-service scores.

PMID- 21855943
TI  - Vitamin D deficiency in the urological population: a single center analysis.
AB  - PURPOSE: Vitamin D has a well-known role in calcium metabolism and bone health.
      It may also help prevent a number of chronic diseases, including cardiovascular
      disease, diabetes and malignancies such as breast, colorectal and prostate
      cancer. To our knowledge the prevalence of vitamin D deficiency has never been
      reported in the general urological population. We evaluated the vitamin D status
      of this population at a large academic center. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 3,763 male and female patients from a
      urology database at a single academic institution. Patients were identified whose
      levels of serum 25-hydroxyvitamin D were measured for the first time between 1997
      and 2010. We determined the prevalence of normal--greater than 30, insufficient-
      20 to 29 and deficient--less than 20 ng/ml 25-hydroxyvitamin D. Logistic
      regression analysis was performed to identify risk factors for vitamin D
      deficiency. RESULTS: Overall 2,559 patients (68%) had suboptimal 25
      hydroxyvitamin D (less than 30 ng/ml), of whom 1,331 (52%) were frankly deficient
      (less than 20 ng/ml) in the vitamin. Vitamin D deficiency was more common in
      patients younger than age 50 years (44.5%), black (53.2%) and Hispanic (41.6%)
      patients (p <0.001), and patients without an existing urological malignancy
      (35.4%, p <0.001). On multivariate analysis race, age, season and cancer
      diagnosis were independent predictors of vitamin D status. CONCLUSIONS: Vitamin D
      deficiency is extremely common in urological patients at a major urban medical
      center. Urologists should consider recommending appropriate supplementation
      during the initial assessment of all patients.

PMID- 21855944
TI  - Nephron sparing surgery for synchronous bilateral nephroblastoma involving the
      renal hilus.
AB  - PURPOSE: Bilateral nephroblastoma involving the renal hilus represents a
      significant surgical challenge. Different operative strategies have been proposed
      for this condition. We analyzed the outcome of simultaneous bilateral partial
      nephrectomy for complex stage V nephroblastoma. MATERIALS AND METHODS: We
      retrospectively analyzed patients with bilateral nephroblastoma involving the
      renal hilus operated on at our institution between 2002 and 2008. We assessed
      patient data and surgical and oncologic outcomes. RESULTS: We analyzed data from
      5 patients with a median age of 27 months at surgery (range 13 to 58). Two
      children had additional pulmonary metastases. Patients were treated according to
      the International Society of Pediatric Oncology 2001/German Society of Pediatric
      Oncology and Hematology protocol. All children underwent synchronous bilateral
      nephron sparing surgery (longitudinal partial nephrectomy or enucleation) of the
      central tumors. Median operating time was 182 minutes (range 129 to 291), with
      vascular exclusion performed in 4 patients (7 to 25 minutes). Complications
      consisted of urinary leakage in 2 cases. Postoperative renal function was
      unimpaired in 4 patients and 1 patient had Wilms tumor/aniridia/genitourinary
      malformations/retardation syndrome with glomerulopathy. One patient with
      pulmonary metastases and blastemal histology had multiple pulmonary relapses and
      died due to pulmonary progressive disease. Four patients are alive without
      evidence of disease at a median followup of 45 months (range 44 to 73).
      CONCLUSIONS: Surgery for central stage V nephroblastoma is possible with good
      functional and oncologic outcomes. The single stage approach is safe, provided
      that operating and treating physicians have sufficient expertise with such
      conditions. The ultimate goal is to avoid tumor nephrectomy.

PMID- 21855946
TI  - Design, implementation and evaluation of a new core learning objectives
      curriculum for a urology clerkship.
AB  - PURPOSE: Until recently, medical students at the University of Wisconsin School
      of Medicine and Public Health participated in a traditional 2-week urology
      clerkship. We hypothesized that a new curriculum with core learning objectives
      and student oriented didactic sessions would increase learning and satisfaction
      compared to a traditional clerkship. MATERIALS AND METHODS: Between July 2008 and
      June 2009, 55 medical students completed the urology clerkship following the
      traditional curriculum. Between July 2009 and June 2010, 51 students followed the
      core learning objectives curriculum. We compared the curriculum outcomes using
      objective and subjective measures. Overall student participation was 90%, with 95
      of 106 students completing both assessment tools. RESULTS: The objective scores
      of the students following the core learning objectives were higher than those of
      the students following the traditional curriculum. The t test to evaluate the
      difference between the 2 curricula was statistically significant (t = 2.845, df =
      93, p <0.05). Subjective scores for the core learning objectives group were lower
      in all but 1 category. Student perception of knowledge attainment for the core
      learning objectives cohort was higher than that of the traditional cohort, but
      none of the subjective scores was statistically significant. CONCLUSIONS: This
      study demonstrated that a core learning objectives curriculum was associated with
      higher objective test scores compared to a traditional model, suggesting that the
      core learning objectives curriculum increased student learning compared to the
      traditional curriculum. However, the core learning objectives cohort did not show
      greater satisfaction than students following the traditional curriculum.

PMID- 21855945
TI  - Use of ureteral stent in extracorporeal shock wave lithotripsy for upper urinary
      calculi: a systematic review and meta-analysis.
AB  - PURPOSE: This systematic review was performed to assess the necessity and
      complications of stenting before extracorporeal shock wave lithotripsy in the
      management of upper urinary stones. MATERIALS AND METHODS: A systematic research
      of PubMed(r), EMBASE(r) and the Cochrane Library was performed to identify all
      randomized controlled trials. The comparisons were about the outcomes and
      complications of extracorporeal shock wave lithotripsy in the management of upper
      urinary stones with or without Double-J stenting before extracorporeal shock wave
      lithotripsy, including stone-free rate, Steinstrasse, lower urinary tract
      symptoms, hematuria, fever, urinary tract infection, pain and analgesia,
      auxiliary treatment, and nausea and vomiting. We used the Cochrane
      Collaboration's Review Manager (RevMan) 5.0.2 software for statistical analysis.
      RESULTS: Eight randomized controlled trials were included in analysis that
      reported 876 patients in total, divided into the stented group of 453 and the
      stentless group of 423. All studies recorded the stone-free rate and the results
      of the meta-analysis showed no difference between the groups (RR 0.97, 95% CI
      0.91-1.03, p = 0.27). The total incidence of Steinstrasse in the stented group
      was similar to that of the stentless group with the exception of 1 study.
      However, the incidence of lower urinary tract symptoms was significantly higher
      in the stented group than in the stentless group (RR 4.10, 95% CI 2.21-7.61, p
      <0.00001). Significant differences could not be found in hematuria, fever,
      urinary tract infection, pain and analgesia, auxiliary treatment, or nausea and
      vomiting between the groups. CONCLUSIONS: The systematic review suggested
      significant advantages of stenting before extracorporeal shock wave lithotripsy
      compared to in situ extracorporeal shock wave lithotripsy in terms of
      Steinstrasse. However, stenting did not benefit stone-free rate and auxiliary
      treatment after extracorporeal shock wave lithotripsy, and it induced more lower
      urinary tract symptoms. More high quality, randomized controlled trials are
      needed to address this issue.

PMID- 21855947
TI  - High incidence of predominant Gleason pattern 4 localized prostate cancer is
      associated with low serum testosterone.
AB  - PURPOSE: We characterized the aggressiveness of prostate cancer by Gleason score
      and predominant Gleason pattern in relation to preoperative serum testosterone.
      MATERIALS AND METHODS: In a prospective study serum total testosterone was
      measured preoperatively in patients referred to our department from January 2007
      to January 2011 for radical prostatectomy. Gleason score and predominant Gleason
      pattern were determined in prostate biopsy and prostate tissue specimens.
      RESULTS: A total of 431 patients were enrolled in the study. In biopsies a
      predominant Gleason pattern 4 was observed in 72 patients (17%). In prostate
      specimens the predominant Gleason pattern 4 increased to 132 patients (31%). In
      the 132 patients total testosterone was lower than in the 299 with predominant
      Gleason pattern 3 (4.00 vs 4.50 ng/ml, p = 0.001), prostate specific antigen was
      higher (8.4 vs 6.6 ng/ml, p <0.00001), and extraprostatic extension and positive
      margins were noted more often (49% vs 20% and 23% vs 14%, p <0.000001 and 0.02,
      respectively). The 62 patients with total testosterone less than 3.0 ng/ml were
      larger (mean 7 kg, p = 0.0001) with a higher body mass index (mean 0.5 kg/m(2), p
      <0.000001). They had a higher percent of Gleason score with predominant Gleason
      pattern 4 (47% vs 28%, p = 0.002). CONCLUSIONS: Low total testosterone is
      associated with a higher percent of predominant Gleason pattern 4, a signature of
      prostate cancer aggressiveness. Tumor aggressiveness cannot be accurately
      estimated by biopsy Gleason score and predominant Gleason pattern. Preoperative
      total testosterone should be added to prostate specific antigen determination to
      improve management for prostate cancer.

PMID- 21855948
TI  - Excessive nocturnal urine production is a major contributing factor to the
      etiology of nocturia.
AB  - PURPOSE: Nocturnal polyuria is a common but often overlooked cause of nocturia.
      We investigated the proportion of adults with 2 or greater voids nightly who had
      nocturnal polyuria in 2 cohorts from the United States and Europe. MATERIALS AND
      METHODS: Data on nocturnal polyuria were obtained from 3 or 7-day frequency
      volume charts completed by patients as part of screening for inclusion in
      subsequent trials of nocturia therapy. Patients recorded the time and volume of
      each void. Nocturnal polyuria was defined as nocturnal urine volume greater than
      33% of 24-hour volume, including the first morning void. RESULTS: In the first
      cohort 1,003 patients were screened, of whom 846 provided evaluable diary data,
      including 641 (76%) with nocturnal polyuria. Of the total screened population of
      1,003 patients 641 (64%) had confirmed nocturnal polyuria. The prevalence of
      nocturnal polyuria increased with age but was high in all age groups. In the
      second cohort 1,412 patients were screened, of whom 917 provided evaluable diary
      data, including 806 (88%) with nocturnal polyuria. Of the total screened
      population of 1,412 patients 806 (57%) had confirmed nocturnal polyuria. The
      prevalence of nocturnal polyuria increased with age but was high in all age
      groups. Of 158 patients receiving benign prostatic hyperplasia and/or overactive
      bladder medication 141 (89%) had nocturnal polyuria. In each cohort the nocturnal
      polyuria prevalence was high in all ethnic groups (63% or greater). CONCLUSIONS:
      In this large study nocturnal polyuria was present in most patients with nocturia
      regardless of gender, age, ethnicity, country and concomitant benign prostatic
      hyperplasia/overactive bladder therapy.

PMID- 21855949
TI  - Effect of failed initial closure on bladder growth in children with bladder
      exstrophy.
AB  - PURPOSE: Failed initial bladder exstrophy closure may hinder the natural course
      of bladder growth compared to successful primary reconstruction. By measuring
      successive bladder capacities within the first 5 years of life, we compared the
      rate of bladder growth in children with failed vs successful initial closure.
      MATERIALS AND METHODS: We used an approved bladder exstrophy database to identify
      and review retrospectively patients with classic bladder exstrophy who underwent
      repeat cystograms between ages 1 and 6 years. Two groups of patients were
      identified--those with successful neonatal closure (group 1) and those with
      successful reclosure after an initial failed procedure (group 2). A generalized
      linear mixed model was fit to evaluate the impact of treatment group and age on
      bladder growth. RESULTS: We identified 48 patients in group 1 (75% male) and 62
      in group 2 (71% male). Initial pelvic osteotomy was done in 60% of group 1 and
      34% of group 2. Patients in group 1 had significantly larger cystographic
      capacity at 2, 4, 5 and 6 years after successful bladder closure compared to
      those in group 2 (p <0.05). The bladder tended to grow at a significantly slower
      rate in group 2 (9.38 cc yearly) compared to group 1 (14.76 cc yearly, p =
      0.005). CONCLUSIONS: Patients with initial failed bladder exstrophy closure
      showed significantly smaller cystographic capacities and slower bladder growth
      compared to those who underwent successful neonatal bladder closure. These data
      clearly underscore the importance of a secure, successful primary closure.

PMID- 21855950
TI  - Comparison of complications of laparoscopic versus laparoendoscopic single site
      donor nephrectomy using the modified Clavien grading system.
AB  - PURPOSE: We compared postoperative complications of laparoendoscopic single site
      and standard laparoscopic living donor nephrectomy using a standardized
      complication reporting system. MATERIALS AND METHODS: We retrospectively analyzed
      the records of consecutive patients who underwent a total of 663 laparoscopic
      living donor nephrectomies and 101 laparoendoscopic single site donor
      nephrectomies. All data were recorded retrospectively. The 30-day complication
      rate was compiled and graded using the modified Clavien complication scale.
      Multivariate binary logistic regression was used to determine independent
      predictors of complications. RESULTS: Baseline demographics were comparable
      between the groups. Compared to those with laparoscopic living donor nephrectomy
      patients who underwent laparoendoscopic single site donor nephrectomy had a
      shorter hospital stay and less estimated blood loss but longer operative time (p
      <0.05) as well as higher oral but lower intravenous in hospital analgesic
      requirements (p <0.05). Mean warm ischemia time was marginally lower in the
      laparoendoscopic single site donor nephrectomy group (3.9 vs 4 minutes, p =
      0.03). At 30 days there was no difference in the overall complication rate
      between the laparoscopic living and laparoendoscopic single site donor
      nephrectomy groups (7.1% vs 7.9%, p >0.05). There were 8 major complications
      (grade 3 to 5) in the laparoscopic living donor nephrectomy group but only 1 in
      the laparoendoscopic single site group. Multivariate binary logistic regression
      analysis revealed that estimated blood loss was a predictor of fewer
      complications at 30 days. CONCLUSIONS: With appropriate patient selection and
      operative experience laparoendoscopic single site donor nephrectomy may be a safe
      procedure associated with postoperative outcomes similar to those of laparoscopic
      living donor nephrectomy as well as low morbidity. Using a standardized
      complication system can aid in counseling potential donors in the future.

PMID- 21855951
TI  - Identification of anti-inflammatory constituents in Hypericum perforatum and
      Hypericum gentianoides extracts using RAW 264.7 mouse macrophages.
AB  - Hypericum perforatum (St. John's wort) is an herb widely used as supplement for
      mild to moderate depression. Our prior studies established synergistic anti
      inflammatory activity associated with 4 bioactive compounds in a fraction of a H.
      perforatum ethanol extract. Whether these 4 compounds also contributed to the
      ethanol extract activity was addressed in the research reported here. Despite the
      popularity of H. perforatum, other Hypericum species with different phytochemical
      profiles could have their anti-inflammatory potentials attributed to these or
      other compounds. In the current study, ethanol extracts of different Hypericum
      species were compared for their inhibitory effect on LPS-induced prostaglandin E2
      (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among
      these extracts, those made from H. perforatum and H. gentianoides demonstrated
      stronger overall efficacy. LC-MS analysis established the 4 compounds were
      present in the H. perforatum extract and pseudohypericin in all active fractions.
      The 4 compounds accounted for a significant part of the extract's inhibitory
      activity on PGE2, NO, tumor necrosis factor-alpha (TNF-alpha), and interleukin
      1beta (IL-1beta) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin
      was the most important contributor of the anti-inflammatory potential among the 4
      compounds. The lipophilic fractions of H. gentianoides extract, which did not
      contain the previously identified active constituents, decreased PGE2 and NO
      potently. These fractions were rich in acylphloroglucinols, including uliginosin
      A that accounted for a proportion of the anti-inflammatory activity observed with
      the active fractions. Overall, the current study established that a different
      group of major anti-inflammatory constituents were present in H. gentianoides,
      while showing that the previously identified 4 compound combination was important
      for H. perforatum's anti-inflammatory potential.

PMID- 21855952
TI  - Interconversions of different forms of vitamin B6 in tobacco plants.
AB  - There are six different vitamin B(6) (VB(6)) forms, pyridoxal (PL), pyridoxamine
      (PM), pyridoxine (PN), pyridoxal 5'-phosphate (PLP), pyridoxamine 5'-phosphate
      (PMP), and pyridoxine 5'-phosphate (PNP), of which PLP is the active form.
      Although plants are a major source of VB(6) in the human diet, and VB(6) plays an
      important role in plants, the mechanisms underlying the interconversions of
      different VB(6) forms are not well understood. In this study, in vitro tobacco
      plants were grown on Murashige and Skoog (MS) basal media supplemented with
      100mg/L of PM, PL or PN and the abundance of the different B(6) vitamers in leaf
      tissue was quantified by high performance liquid chromatography (HPLC). The total
      amount of VB(6) was about 3.9 MUg/g fresh weight of which PL, PM, PN, PLP and PMP
      accounted for 23%, 14%, 37%, 20% and 6%, respectively. Tobacco plants contained a
      trace amount of PNP. Supplementation of the culture medium with any of the non
      phosphorylated vitamers resulted in an increase in total VB(6) by about 10-fold,
      but had very little impact on the concentrations of the endogenous phosphorylated
      vitamers. Administration of either PM or PN increased their endogenous levels
      more than the levels of any other endogenous B(6) vitamers. PL supplementation
      increased the levels of plant PN and PM significantly, but not that of PL,
      suggesting that efficient conversion pathways from PL to PN and PM are present in
      tobacco. Additionally, maintenance of a stable level of PLP in the plant is not
      well-correlated to changes in levels of non-phosphorylated forms.

PMID- 21855953
TI  - Curtains.
AB  - A 55-year-old immunocompetent man presented with headache, nausea, progressive
      bilateral upper lid ptosis, and diplopia. Examination showed bilateral asymmetric
      upper lid ptosis with limited adduction and elevation of both eyes. Cranial
      magnetic resonance imaging revealed enhancing intra-axial and extra-axial
      midbrain lesions. Blood and cerebrospinal fluid were positive for cryptococcal
      antigen and cerebrospinal fluid fungal cultures grew Cryptococcus neoformans.
      Treatment with liposomal amphotericin B and flucytosine resulted in complete
      resolution of his neurological deficits and lesions on neuroimaging. Patients
      with cryptococcal meningitis may rarely present with bilateral cranial nerve III
      dysfunction.

PMID- 21855954
TI  - Evaluation of enhanced coagulation pretreatment to improve ozone oxidation
      efficiency in wastewater.
AB  - Enhanced coagulation (EC) using ferric chloride was evaluated as a pretreatment
      process to improve the efficiency of ozone (O3) for the oxidation of trace
      organic contaminants in wastewater. At the applied dosages (10-30 mg/L as Fe), EC
      pretreatment removed between 10 and 47% of the dissolved organic carbon (DOC)
      from the three wastewaters studied. Size exclusion chromatography (SEC) showed
      that EC preferentially removed higher apparent molecular weight (AMW) compounds.
      Subsequent O3 testing was performed using an O3:DOC ratio of 1. Results showed
      that O3 exposures were similar even though the required doses were reduced by 10
      47% by the EC pretreatment process. Hydroxyl radical (HO.) exposure, measured by
      parachlorobenzoic acid (pCBA), showed 10% reduction when using a FeCl3 dose of 30
      mg/L, likely due to the lower O3 dose and decreased production of HO. during the
      initial phase of O3 decomposition (t<30 s). The oxidation of 13 trace organic
      contaminants (including atenolol, carbamazepine, DEET, diclofenac, dilantin,
      gemfibrozil, ibuprofen, meprobamate, naproxen, primidone, sulfamethoxazole,
      triclosan, and trimethoprim) was evaluated after EC and O3 treatment. EC was
      ineffective at removing any of the contaminants, while O3 oxidation reduced the
      concentration of compounds according to their reaction rate constants with O3 and
      HO..

PMID- 21855955
TI  - Methanogen community structure-activity relationship and bioaugmentation of
      overloaded anaerobic digesters.
AB  - Accumulation of acids in anaerobic digesters after organic overload can inhibit
      or stop CH4 production. Therefore, methods to reduce acid concentrations would be
      helpful. One potential method to improve recovery involves bioaugmentation,
      addition of specific microorganisms to improve performance. In this study,
      transiently overloaded digesters were bioaugmented with a propionate-degrading
      enrichment culture in an effort to decrease recovery time. Biomass samples from
      14 different, full-scale anaerobic digesters were screened for specific
      methanogenic activity (SMA) against propionate; the microbial communities were
      also compared. SMA values spanned two orders of magnitude. Principal component
      analysis of denaturing gradient gel electrophoresis (DGGE) banding patterns for a
      functional gene (mcrA) suggested an underlying community structure-activity
      relationship; the presence of hydrogenotrophic methanogens closely related to
      Methanospirillum hungatei and Methanobacterium beijingense was associated with
      high propionate SMA values. The biomass sample demonstrating the highest SMA was
      enriched for propionate degrading activity and then used to bioaugment overloaded
      digesters. Bioaugmented digesters recovered more rapidly following the organic
      overload, requiring approximately 25 days (2.5 solids retention times (SRTs))
      less to recover compared to non-bioaugmented digesters. Benefits of
      bioaugmentation continued for more than 12 SRTs after organic overload.
      Bioaugmentation is a promising approach to decrease recovery time after organic
      overload.

PMID- 21855956
TI  - Development of a rapid DNA extraction method and one-step nested PCR for the
      detection of Naegleria fowleri from the environment.
AB  - Naegleria fowleri is a small free-living amoebo-flagellate found in natural and
      manmade thermal aquatic habitats worldwide. The organism is pathogenic to man
      causing fatal primary amoebic meningoencephalitis (PAM). Infection typically
      results from bathing in contaminated water and is usually fatal. It is,
      therefore, important to identify sites containing N. fowleri in the interests of
      preventive public health microbiology. Culture of environmental material is the
      conventional method for the isolation of N. fowleri but requires several days
      incubation and subsequent biochemical or molecular tests to confirm
      identification. Here, a nested one-step PCR test, in conjunction with a direct
      DNA extraction from water or sediment material, was developed for the rapid and
      reliable detection of N. fowleri from the environment. Here, the assay detected
      N, fowleri in 18/109 river water samples associated with a nuclear power plant in
      South West France and 0/10 from a similar site in the UK. Although culture of
      samples yielded numerous thermophilic free-living amoebae, none were N. fowleri
      or other thermophilic Naegleria spp. The availability of a rapid, reliable and
      sensitive one-step nested PCR method for the direct detection of N. fowleri from
      the environment may aid ecological studies and enable intervention to prevent PAM
      cases.

PMID- 21855957
TI  - Polycyclic aromatic hydrocarbons (PAHs) in urban surface dust of Guangzhou,
      China: Status, sources and human health risk assessment.
AB  - Ninety-six urban surface dust samples collected from Guangzhou, a typical urban
      center in South China, were analyzed for 16 PAHs (2-6 rings). ?PAHs
      concentrations in the urban surface dust ranged from 0.84 to 12.3MUg/g with a
      mean of 4.80MUg/g. High molecular weight compounds (4-6 rings) contributed to 62
      to 94% of ?PAHs mass in the surface dust samples. Four hotspots with highest
      ?PAHs were identified via kriging prediction mapping, representing the highly
      urbanized regions: central downtown, highway and industrial area. Two major
      origins of PAHs inputs to urban surface dust were identified as vehicle emissions
      (51.9%) and coal combustion (26.8%). The 95% UCL of Incremental Lifetime Cancer
      Risk (ILCR) due to human exposure to urban surface dust PAHs in central South
      China was 3.03*10(-6) for children and 2.92*10(-6) for adults.

PMID- 21855958
TI  - Atmospheric polybrominated diphenyl ethers (PBDEs) and Pb isotopes at a remote
      site in Southwestern China: implications for monsoon-associated transport.
AB  - A 13-month sampling campaign was conducted at a remote site in southwestern China
      from October, 2005 to December, 2006. An integrated approach with lead isotopes
      and air back trajectory analysis was used to investigate the monsoon-associated
      atmospheric transport of PBDEs in tropical/subtropical Asia regions. The air
      concentration of PBDEs ranged from 1.6 to 57.5 pgm(-3) (15.9+/-12.0 pgm(-3)),
      comparable to reported levels at other remote sites in the world. BDE-209,
      followed by BDE-47 and -99 dominated the PBDE compositions, indicating a mixed
      deca- and penta-BDE source. Air mass back trajectory analysis revealed that the
      major potential source regions of BDE-47 and -99 could be southern China and
      Thailand, while those of BDE-209 are widely distributed in industrialized and
      urbanized areas in tropical Asia. The different lead isotope compositions of
      aerosols between trajectory clusters further substantiated the observation that
      the South Asian monsoon from spring to summer could penetrate deep into
      southwestern China, and facilitate long-range transport of airborne pollutants
      from South Asia.

PMID- 21855959
TI  - Classic and novel brominated flame retardants (BFRs) in common sole (Solea solea
      L.) from main nursery zones along the French coasts.
AB  - Brominated flame retardants (BFRs) were investigated in juvenile common sole from
      nursery zones situated along the French coast in 2007, 2008 and 2009. Extensive
      identification was performed with regard to PBDEs, novel BFRs 1,2-bis(2,4,6
      tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE), and other non
      PBDE BFRs, namely, hexabromobenzene (HBB) and 2,2',4,4',5,5'-hexabromobiphenyl
      (BB-153). Polybrominated diphenyl ether (PBDE) concentrations (Sigma 14
      congeners) ranged from 0.01 ng/g to 0.16 ng/g wet weight (ww) in muscle, and 0.07
      ng/g to 2.8 ng/g ww in liver. Concentrations were in the lower range of those
      reported in the literature in other European locations. Lower PBDE
      concentrations, condition indices and lipid contents were observed in the Seine
      estuary in 2009, possibly in relation to a lower water flow. The PBDE patterns
      and ratios we observed suggested that juvenile sole have a relative high
      metabolic degradation capacity. Non-PBDE BFRs were detected at lower levels than
      PBDEs, i.e., within the < method detection limit - 0.005 ng/g ww range in muscle,
      and < method detection limit - 0.2 ng/g ww range in liver. The data obtained is
      of particular interest for the future monitoring of these compounds in the
      environment.

PMID- 21855960
TI  - Modelling transport and transformation of mercury fractions in heavily
      contaminated mountain streams by coupling a GIS-based hydrological model with a
      mercury chemistry model.
AB  - Many heavily polluted areas are located in remote regions that lack routine
      hydrologic monitoring. A modelling method that can produce scenarios of water
      chemistry trends for regions that lack hydrological data is therefore needed. The
      Wanshan mining area, in Guizhou province in south-western China, is such a
      region, as it is heavily polluted with mercury (Hg). In order to model Hg
      transport in a stream draining the Wanshan mining area, a Geographic Information
      System (GIS) hydrologic model (HEC-HMS) was coupled with a simulation model for
      Hg fractions in water (WASP Hg). Hydrological variations in the stream flow can
      thereby be simulated based on readily available precipitation data. The WASP 7
      MERC Hg model was used for simulating variations in total Hg, dissolved Hg and
      methyl-Hg concentrations. The results of HEC-HMS modelling of flow show clear
      seasonal variation. Winter (Oct-Dec) constitutes the dry season with low flow,
      while the summer season (Jun-Aug) is rainy with high flow. 48% of total annual
      precipitation happens in the three summer months. The stream flows at the high
      flow events were several times higher than normal flow. The modelled total
      suspended solids and Hg concentrations were tested against monitoring data from
      two sampling campaigns conducted in September 2007 and August 2008. The model
      produced reasonable simulations for TSS, THg, DHg and MeHg, with relative errors
      generally around 10% for the modelled parameters. High flow events are the main
      contributors for release of both suspended particles and Hg. The three high flow
      events account for about 50% of annual discharge of THg. The annual total
      discharge of Hg was 8.8 kg Hg high up in the stream and 2.6 kg where the stream
      meets a large river 20 km downstream of the pollution source. Hence, about 70% of
      Hg is retained in the stream through sedimentation.

PMID- 21855961
TI  - Cu-doped TiO(2) nanoparticles enhance survival of Shewanella oneidensis MR-1
      under ultraviolet light (UV) exposure.
AB  - It has been shown that photocatalytic TiO(2) nanoparticles (NPs) can be used as
      an efficient anti-microbial agent under UV light due to generation of reactive
      oxygen species (ROS), while Shewanella oneidensis MR-1 is a metal-reducing
      bacterium highly susceptible to UV radiation. Interestingly, we found that the
      presence of Cu-doped TiO(2) NPs in the cultural medium dramatically increased the
      survival rates (based on colony-forming unit) of strain MR-1 by over 10,000-fold
      (incubation without shaking) and ~200 fold (incubation with shaking) after a 2-h
      exposure to UV light. Gene expression results (via qPCR measurement) indicated
      that the DNA repair gene recA in MR-1 was significantly induced by UV exposure
      (indicating cellular damage under UV stress), but the influence of NPs on recA
      expression was not statistically evident. Plausible explanations to NP
      attenuation of UV stresses are: 1. TiO(2) based NPs are capable of scattering and
      absorbing UV light and thus create a shading effect to protect MR-1 from UV
      radiation; 2. more importantly, Cu-doped TiO(2) NPs can co-agglomerate with MR-1
      to form large flocs that improves cells' survival against the environmental
      stresses. This study improves our understanding of NP ecological impacts under
      natural solar radiation and provides useful insights to application of
      photocatalytic-NPs for bacterial disinfection.

PMID- 21855962
TI  - Carbon air pollution reflected in deposits on chosen building materials of Prague
      Castle.
AB  - Thin black surface layers or black coloured gypsum crusts can be observed on
      stones of many buildings and sculptures around the world. The black weathered
      stone and mortar surface from selected sections of the Prague Castle were studied
      by microscopic methods, GC/MS and pyrolysis-GC/MS analysis. Microscopically, we
      found an authigenic gypsum formation with an outer layer of an admixture of fine
      grains of quartz, clay minerals, thermally altered clay minerals, fly ash, and
      carbonaceous particles of natural and anthropogenic origin particularly chars,
      cokes, soots. Noncarbonate C content ranged between 0.8% and 4.3%. Phtalates
      dominated in extracts from the samples and benzonitrile had the greatest
      abundance in the pyrolysis products. The identified organic particles and
      compounds are known to result from human activities.

PMID- 21855963
TI  - Temporal variation of pharmaceuticals in an urban and agriculturally influenced
      stream.
AB  - Pharmaceuticals have become ubiquitous in the aquatic environment. Previous
      studies consistently demonstrate the prevalence of pharmaceuticals in freshwater
      but we do not yet know how concentrations vary over time within a given system.
      Two sites in central Indiana with varying land use in the surrounding watershed
      (suburban and agricultural) were sampled monthly for pharmaceutical
      concentrations and stream physiochemical parameters. Sediment samples were also
      collected at each sampling event for measurement of delta(15)N natural abundance
      and sediment organic content. Across sites and sampling events, twelve
      pharmaceuticals were detected including acetaminophen, caffeine, carbamazepine,
      cotinine, N,N-diethyl-meta-toluamide (DEET), gemfibrozil, ibuprofen,
      sulfadimethoxine, sulfamethazine, sulfamethoxazole, triclosan, and trimethoprim.
      Sulfathiazole, lincomycin, and tylosin were not detected at either site at any
      time. The agriculturally-influenced site had comparable pharmaceutical
      concentrations to the urban-influenced site. In general, pharmaceutical
      concentrations increased during winter at both sites and decreased during spring
      and summer. Multiple regression analyses indicated that water column dissolved
      oxygen, the number of days since precipitation, and solar radiation influenced
      total pharmaceutical concentration in the urban-influenced site; whereas pH,
      chlorophyll a concentration, and total amount of rainfall in the previous 10 days
      influenced total pharmaceutical concentrations in the agriculturally-influenced
      site. Pharmaceutical concentrations were not correlated with sediment delta(15)N
      across or within sites. However, sediment in the urban-influenced site had higher
      mean delta(15)N signatures relative to sediment in the agriculturally-influenced
      site. These data indicate pharmaceuticals are persistent in aquatic ecosystems
      influenced by both agricultural and suburban activity. Pharmaceuticals are
      designed to have a physiological effect; therefore, it is likely that they may
      also influence aquatic organisms, potentially threatening freshwater ecosystem
      health.

PMID- 21855964
TI  - Expression of macro non-coding RNAs Meg8 and Irm in mouse embryonic development.
AB  - Non-coding RNAs (ncRNAs) Meg8 and Irm were previously identified as alternatively
      splicing isoforms of Rian gene. Ascertaining ncRNAs spatiotemporal expression
      patterns is crucial for understanding the physiological roles of ncRNAs during
      tissue and organ development. In this study in mouse embryos, we focused on the
      developmental regulation expression of imprinted macro ncRNAs, Meg8 and Irm by
      using in situ hybridization and quantitative real-time RT-PCR (QRT-PCR). The in
      situ hybridization results showed that Meg8 and Irm were expressed in the
      developing brain at embryonic day 10.5 (E10.5) and E11.5, while Irm expression
      signals were strikingly detected in the somite, where Meg8 expression signals
      were undetectable. By E15.5, they were expressed in brain, tongue, liver, lung
      and neuroendocrine tissues, while Irm displayed more restricted expression in
      tongue and skeletal muscle than Meg8. Furthermore, quantitative analysis
      confirmed that they were highly expressed in tongue and brain at E12.5, E15.5 and
      E18.5. These results indicated that Meg8 and Irm might be coordinately expressed
      and functionally correlated in diverse of organs. Notably, Irm was more closely
      associated with morphogenesis of skeletal muscle in contrast to Meg8 during
      embryonic development.

PMID- 21855965
TI  - Prediction of morbidity and mortality after percutaneous nephrolithotomy by using
      the Charlson Comorbidity Index.
AB  - OBJECTIVES: To determine whether the Charlson Comorbidity Index (CCI) predicts
      postoperative medical complications and death in patients treated with
      percutaneous nephrolithotomy (PCNL). METHODS: A total of 1406 PCNL procedures
      were performed at 4-stone referral centers between September 2004 and March 2011
      were reviewed in this multicenter study. Variables included patient and stone
      characteristics, preoperative comorbidities, intraoperative data, and
      postoperative complications, including mortality. RESULTS: The present study
      included 868 (61.7%) men and 538 (38.3%) women. Mean patient age was 44.1 years
      (range 1-81). CCI score was calculated as "0" for 993 patients (70.6%, called
      group I), "1" for 316 patients (22.5%, called group II) and">=2" for 97 patients
      (6.9%, called group III). The incidence of comorbidities increased with age
      (P=.001). The overall postoperative complication rate was 29.3%. Life-threatening
      medical complications developed in 2.9% of patients in group I, 7.6% of patients
      in group II, and 21.6% of patients in group III, (P=.001). There were 3 deaths
      for an overall 0.2% mortality rate. Perioperative bleeding requiring blood
      transfusion was observed in 9.5% of patients, and we found an increased risk of
      hemorrhage associated with CCI score (P=.049). High CCI score, patient age,
      hemorrhage, and operative time were significantly related to higher medical
      complication rates after PCNL. CONCLUSIONS: CCI is a quick, simple, and
      reproducible scoring system that accurately predicts the morbidity and mortality
      of PCNL.

PMID- 21855966
TI  - Interstitial cystitis/bladder pain syndrome and nonbladder syndromes: facts and
      hypotheses.

PMID- 21855967
TI  - Robotic versus laparoscopic partial nephrectomy for bilateral synchronous kidney
      tumors: single-institution comparative analysis.
AB  - OBJECTIVE: To compare the intraoperative and early postoperative outcomes of
      robotic partial nephrectomy (RPN) with those of laparoscopic partial nephrectomy
      (LPN) outcomes in patients with bilateral synchronous renal tumors. RPN is
      emerging as an attractive minimally invasive nephron-sparing approach for renal
      tumors. METHODS: Our ongoing institutional review board-approved, prospectively
      maintained, kidney cancer database was used to identify the study population. The
      medical records of patients who underwent minimally invasive nephron-sparing
      surgery at our institution from January 2001 to March 2010 were used. A cohort of
      9 patients undergoing bilateral RPN was identified and compared with 17
      consecutive patients who underwent sequential bilateral LPN. The demographic,
      intraoperative, postoperative, and short-term renal functional data were
      retrospectively compared between the 2 groups. RESULTS: A total of 18 procedures
      were performed in the RPN group and 32 in the LPN group. The median warm ischemia
      time was shorter in the RPN group than in the LPN group (19 vs 37 minutes,
      respectively; P = .059). The median tumor size was 2.85 and 2.7 cm in the RPN and
      LPN group, respectively (P = .03). The final median postoperative glomerular
      filtration rate was 68.7 mL/min/1.73 m(2) (interquartile range 14-73) and 26.9
      mL/min/1.73 m(2) (interquartile range 20-70) in the RPN and LPN groups,
      respectively (P = .004). No difference was found in the complications in the RPN
      group (n = 2) compared with the LPN group (n = 4). CONCLUSION: RPN is a safe and
      effective minimally invasive nephron-sparing treatment of bilateral synchronous
      kidney tumors. A trend was seen toward a shorter warm ischemia time and less
      effects on postoperative renal function compared with the laparoscopic approach.

PMID- 21855968
TI  - The impact of pelvicaliceal anatomy on the success of retrograde intrarenal
      surgery in patients with lower pole renal stones.
AB  - OBJECTIVES: To evaluate the impact of pelvicaliceal anatomy on the success of
      retrograde intrarenal surgery (RIRS) for lower pole renal stones and determine
      which of these factors can be used to select patients who will benefit from RIRS.
      METHODS: We evaluated 67 patients who underwent RIRS between 2009 and 2010 for
      isolated lower pole renal stones. The infundibular length (IL), infundibular
      width (IW), pelvicaliceal height (PCH), and infundibulopelvic angle (IPA) were
      measured by preoperative intravenous urogram. Success was defined as either
      complete clearance or clearance with insignificant residual fragments<=3 mm in
      size at 2-months follow-up. RESULTS: Mean IL was 26.7+/-7.9 and 28.2+/-5.3 mm,
      mean PCH was 20.7+/-6.6 and 23.2+/-4.9 mm in stone-free and non-stone-free
      patients, respectively. These were slightly larger in the non-stone-free group
      but not statistically significant (P=.140 and P=.072, respectively). Mean IW was
      5.8+/-3.5 and 5.6+/-2.2 mm in stone-free and non-stone-free patients,
      respectively, which had no significant impact on the stone-free rate (P=.719).
      There were significant differences between the groups in terms of stone length
      (P=.001) and IPA (P=.003). The mean IPA was 49.37+/-11.83 and 37.61+/-13.22 mm in
      stone-free and non-stone-free patients, respectively. CONCLUSIONS: In addition to
      the influence of stone size, lower pole anatomy, especially IPA, has a
      significant impact on stone clearance for lower pole stones after RIRS.

PMID- 21855969
TI  - Responsiveness and minimal clinically important change in overactive bladder
      symptom score.
AB  - OBJECTIVE: To assess the responsiveness and minimal clinically important change
      (MCIC) in the Overactive Bladder Symptom Score (OABSS), a single score used to
      quantify overactive bladder symptoms. METHODS: The data were derived from a
      clinical trial of propiverine in patients with overactive bladder. The analysis
      included participants who completed the OABSS, a bladder diary, and patient
      reported outcome measures (urgency and incontinence impact) at baseline and 12
      weeks. Responsiveness was assessed with effect sizes, correlations between the
      OABSS items and bladder diary variables, and comparisons between the score
      changes and symptom improvement. The MCIC was comprehensively estimated from the
      discriminating thresholds for minimal symptom improvement, and the receiver
      operating characteristics curve analyses were used to derive cutoff scores for
      symptom improvement. RESULTS: A total of 282 participants were included in the
      present analysis. The effect sizes for the OABSS ranged from -0.369 to -1.485,
      and correlations between the changes in the OABSS items and the corresponding
      bladder diary variables were moderate to large. A linear tendency was found
      between the changes in the OABSS and symptom improvement. The mean change for
      urgency and incontinence impact was -2.59 and -2.49 for "no change" and -3.67 and
      -3.78 for "minor improvement," respectively. The optimal cutoff score ranged from
      -4 to -3. Integrating the MCIC analyses, -3 was estimated as the minimal
      threshold for a meaningful change. CONCLUSION: With good responsiveness, the
      OABSS is a useful tool for assessing the treatment of OAB symptoms. Furthermore,
      the results of our study suggest that the MCIC of the OABSS is -3.

PMID- 21855970
TI  - Minimal arterial in-flow protects renal oxygenation and function during porcine
      partial nephrectomy: confirmation by hyperspectral imaging.
AB  - OBJECTIVES: To examine the potential for renal protection through incomplete
      renal artery (RA) occlusion with both assessments of creatinine changes and the
      use of hyperspectral imaging to monitor tissue oxygenation. Renal ischemia during
      partial nephrectomy can have adverse consequences on renal function. METHODS:
      Fourteen pigs with a solitary kidney underwent open partial nephrectomy with warm
      ischemia. The RA flow was measured and reduced to 25%, 10%, and 0% of baseline
      for 60 minutes. Hyperspectral imaging was used to assess the percentage of
      oxyhemoglobin (%HbO(2)) at baseline, during ischemia, and during reperfusion. The
      %HbO(2) and change in the serum creatinine level from baseline were compared.
      RESULTS: The baseline RA flow and %HbO(2) were similar in all groups, and, as
      expected, RA occlusion resulted in decreasing %HbO(2). The reduction of RA flow
      to 25% and 10% improved the nadir tissue oxygenation compared with 0% flow (P =
      .01 and P = .04, respectively) and 25% flow also appeared to prolong the interval
      to reach the nadir %HbO(2). Reperfusion resulted in a swift return to the
      baseline %HbO(2) in all 3 groups. The change in the serum creatinine from
      baseline to postoperative day 7 showed significantly improved renal preservation
      in the 25% RA flow group. CONCLUSIONS: Incomplete RA occlusion during porcine
      partial nephrectomy resulted in favorable renal oxygenation profiles with as
      little as 10% blood flow and appeared to be renoprotective when 25% of the
      baseline RA flow is preserved. Hyperspectral imaging is a sensitive, noninvasive
      tool for real-time monitoring of renal oxygenation and, thereby, blood flow,
      which could facilitate intraoperative decision-making to protect kidney function.

PMID- 21855971
TI  - A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian
      cancer.
AB  - BACKGROUND: Previous reports have shown that the proteomic markers apolipoprotein
      A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment,
      transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin
      may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim
      was to determine if these serum proteomic biomarkers alone as well as in
      combination with age and serum CA125, could be helpful in triage of women with a
      pelvic mass. METHODS: We included prospectively 144 patients diagnosed with (OC),
      40 with a borderline tumor and 469 with a benign tumor. Surface-enhanced laser
      desorption/ionization time of flight-mass spectrometry was used for analyses. The
      Danish Index (DK-Index) based on the proteomic data, age and CA125 was developed
      using logistic regression models. RESULTS: Multivariate logistic regression
      analysis demonstrated that the selected proteomic markers, CA125 and age were
      independent predictors of OC and the combination of these is proposed as the DK
      index. A sensitivity (SN) of 99% had a specificity (SP) of 57% for DK-index and
      49% for CA125. At a SN of 95%, the SP increased to 81% for DK-index compared to
      68% for CA125 alone. For stage I+II the SP was 58% for DK-index and 49% for
      CA125. For stage III+IV the corresponding values were 94% and 86% respectively.
      CONCLUSIONS: The DK-index warrants further evaluation in independent cohorts.

PMID- 21855972
TI  - Preoperative staging of cervical cancer: is 18-FDG-PET/CT really effective in
      patients with early stage disease?
AB  - OBJECTIVE: Nodal status is one of the most important findings in patients with
      early-stage cervical cancer that requires post-surgical adjuvant therapies and
      influences prognosis of patients. The purpose of this study was to determine the
      diagnostic accuracy of 18F-fluorodeoxyglucose Positron Emission
      Tomography/Computed Tomography (18F-FDG-PET/CT) in the detection of nodal
      metastases. METHODS: From 2004 to 2010 women with Ib1-IIa <4cm cervical cancer
      underwent 18F-FDG-PET/CT followed by radical hysterectomy and pelvic
      lymphadenectomy in our institution. 18F-FDG-PET/CT images were analyzed and
      histopathological findings served as the reference standard. Diagnostic
      performance of 18F-FDG-PET/CT in nodal disease detection was reported in terms of
      accuracy value. A sub analysis of women with tumor diameter <2cm (group 1) or 2
      4cm (group 2) was performed in order to verify the efficacy of 18F-FDG-PET/CT in
      each group. RESULTS: One hundred fifty-nine women were enrolled. 65% had squamous
      histotype and 51% had grade 3 disease. Median number of nodes dissected was 29
      (range 11-61). 28/159 women (18%) showed nodal metastases. Overall patient-based
      sensitivity, specificity, positive and negative predictive value of 18F-FDG
      PET/CT for detection of nodal disease were 32.1%, 96.9%, 69.2%and 87.0%
      respectively. Among the 97 (61%) women included in group 1, 8 had nodal
      metastases (8.2%) and 2 was discovered through 18F-FDG-PET/CT (25%), while 20/62
      women of the group 2 (32.3%) had nodal involvement, of which 7 (35%) was detected
      by 18F-FDG-PET/CT. CONCLUSIONS: This study showed that 18F-FDG-PET/CT had low
      sensitivity and had a minimal clinical impact in the pretreatment planning of
      stage Ib1-IIa <4cm cervical cancer.

PMID- 21855973
TI  - The effect of sleep disturbance on quality of life in women with ovarian cancer.
AB  - OBJECTIVE: To estimate the prevalence of sleep disturbances, and to determine if
      there is an association between sleep disturbances with quality of life (QOL),
      depression or clinical demographic variables. METHODS: Patients diagnosed with
      ovarian, fallopian tube or primary peritoneal cancer during the last 5years
      completed questionnaires regarding sleep patterns and disturbances [Pittsburgh
      Sleep Quality Index (PSQI)], depression [Beck Depression inventory (BDI)], and
      QOL [The Functional Assessment of Cancer Therapy-Ovarian (FACT-O), fatigue module
      (-F)]. Data were analyzed by Student's t-test or Pearson correlation coefficient
      to determine if there were differences between PSQI score with QOL, depression or
      clinical demographic variables. RESULTS: 86/275 (31% response) of patients
      returned the surveys. Mean age was 58.1 (SD=14.6) years and 70% had advanced
      disease at diagnosis. Thirty-six percent had current disease of which 81% were
      receiving chemotherapy. Sixty-seven percent of patients had a PSQI score>=5
      corresponding to overall poor sleep quality and 46% of patients reported using
      sleep medication at least once during the prior month. PSQI score was
      significantly inversely correlated with all QOL domains (physical: r=-.599,
      p<.001, functional: r=-.692, p<.001, social: r=-.212, p<.001, emotional: r=-.379,
      p<.001, fatigue; r=-.655 p<.001) and with depression (r=.539, p<.001). PSQI was
      not correlated with age, time since diagnosis, number of previous chemotherapy
      regimens. PSQI score did not differ by current disease or chemotherapy status.
      CONCLUSIONS: Sleep disturbances reduce QOL, a prognostic indicator for survival,
      in ovarian cancer patients. These patients should undergo routine screening and
      would benefit from interventions that aim to promote restful sleep.

PMID- 21855974
TI  - Survivors of endometrial cancer: who is at risk for sexual dysfunction?
AB  - OBJECTIVE: Our goal was to determine the prevalence of sexual dysfunction and
      identify risk factors associated with sexual morbidity in patients with early
      stage endometrial cancer. METHODS: This prospective trial included patients with
      stage I-IIIa endometrial cancer, without evidence of disease, and one to five
      years out from primary surgical treatment. Patients who received chemotherapy
      were excluded. The Female Sexual Function Index (FSFI) was used to measure our
      primary endpoint of sexual function. Other patient reported outcome indices
      included: Functional Assessment of Cancer Therapy-Endometrial (FACT-En), Center
      for Epidemiology Studies Depression scale (CES-D), and Menopausal Rating Scale
      (MRS). RESULTS: Of the 72 women treated for early stage endometrial cancer, 65%
      were married, 69% had a sexual partner, the mean age was 60, 86% had stage I
      disease, and 18% received radiation therapy. The median score for the FSFI was
      16.6 (0-32.8; scores below 26 are diagnostic for sexual dysfunction). Eighty nine
      percent of the patients had a score below 26. There was a moderate correlation
      between the total FSFI score and FACT-En scores but not with CES-D or MRS.
      Histologic grade, relationship status, mental health, and diabetes significantly
      correlated with total FSFI scores in multivariate analysis. CONCLUSION: This
      patient population commonly thought to be at low risk actually suffers from
      severe sexual dysfunction. The four risk factors revealed by multivariate
      analysis need to be studied in greater detail in order to appropriately target
      patients and develop meaningful interventions.

PMID- 21855975
TI  - Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen
      sensitization in children from Tucson, Arizona.
AB  - BACKGROUND: The association between vitamin D status at birth and childhood
      allergic outcomes is uncertain. The desert climate of Tucson offers a unique
      setting for studying the health effects of higher exposure to vitamin D.
      OBJECTIVE: To assess the relationship between cord blood 25-hydroxyvitamin D
      (25[OH]D) levels and allergic outcomes through age 5 years. METHODS: Cord blood
      25(OH)D levels were measured in 219 participants in the Tucson Infant Immune
      Study, a population-based birth cohort. Plasma total IgE and specific IgE levels
      to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT)
      positivity (wheal diameter >= 3 mm) and physician-diagnosed active allergic
      rhinitis and asthma were assessed at age 5 years. Longitudinal models were used
      to assess the relationship between 25(OH)D and IgE levels. Logistic regression
      models were used to assess the relationship of 25(OH)D level with SPT positivity,
      allergic rhinitis, and asthma. RESULTS: The median cord blood 25(OH)D level was
      64 nmol/L (interquartile range, 49-81 nmol/L). Relative to the reference group
      (50-74.9 nmol/L), both low (<50 nmol/L) and high (>= 100 nmol/L) levels were
      associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient
      = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE
      (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through
      age 5 years. High 25(OH)D levels were also associated with increased SPT
      positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not
      significantly associated with allergic rhinitis or asthma. CONCLUSION: Both low
      and high levels of cord blood 25(OH)D were associated with increased aeroallergen
      sensitization. The association between vitamin D status and actual allergic
      diseases merits further study.

PMID- 21855976
TI  - Allergic reactions to manioc (Manihot esculenta Crantz): identification of novel
      allergens with potential involvement in latex-fruit syndrome.

PMID- 21855977
TI  - Polymorphisms of the CYP2C19 gene in Japanese patients with aspirin-exacerbated
      respiratory disease.

PMID- 21855978
TI  - It's time to rethink mite allergen avoidance.
AB  - The role of allergen exposure in the etiology of allergic sensitization and
      asthma is complex. Advice on strategies to avoid domestic allergens remains
      contentious because trials of interventions aimed to prevent asthma or reduce
      symptoms have often failed to demonstrate benefits. Asthma management guidelines
      differ widely in their recommendations, while Web-based information often claims
      benefits associated with products. In this rostrum we argue that although many
      factors have a role in both the etiology and the exacerbation of asthma, allergen
      exposure probably remains an important contributor to the manifestations of the
      disease. Currently, there is no evidence-based framework for effective domestic
      allergen avoidance interventions to reduce chronic aeroallergen exposure. The
      development of an effective approach to allergen avoidance requires a better
      understanding of (a) the physical nature of chronic aeroallergen exposure and
      methods for measuring and reducing this, (b) the interaction between allergen
      exposure and innate immune modulators at different disease stages, and (c)
      markers enabling the identification of individuals who would benefit from this.
      The strategic risk of overemphasizing other novel mechanisms and approaches to
      asthma management is that we will prematurely abandon and fail to improve an
      existing approach that could have a significant impact on the development,
      progression, and symptoms of the disease.

PMID- 21855979
TI  - Astrocytes are endogenous regulators of basal transmission at central synapses.
AB  - Basal synaptic transmission involves the release of neurotransmitters at
      individual synapses in response to a single action potential. Recent discoveries
      show that astrocytes modulate the activity of neuronal networks upon sustained
      and intense synaptic activity. However, their ability to regulate basal synaptic
      transmission remains ill defined and controversial. Here, we show that astrocytes
      in the hippocampal CA1 region detect synaptic activity induced by single-synaptic
      stimulation. Astrocyte activation occurs at functional compartments found along
      astrocytic processes and involves metabotropic glutamate subtype 5 receptors. In
      response, astrocytes increase basal synaptic transmission, as revealed by the
      blockade of their activity with a Ca(2+) chelator. Astrocytic modulation of basal
      synaptic transmission is mediated by the release of purines and the activation of
      presynaptic A(2A) receptors by adenosine. Our work uncovers an essential role for
      astrocytes in the regulation of elementary synaptic communication and provides
      insight into fundamental aspects of brain function.

PMID- 21855980
TI  - Comparison of the cytobrush, cottonswab, and low-volume uterine flush techniques
      to evaluate endometrial cytology for diagnosing endometritis in chronically
      infertile mares.
AB  - Endometritis is the most important cause of infertility in barren mares. The
      quick method of endometrial cytology (EC) has a relatively high reliability in
      diagnosing endometrial inflammation in the mare. For reliable cytological
      results, a collection technique that yields many well-preserved cells
      representative of a large uterine surface area without causing harm to the
      reproductive tract is required. The aim of the study was to compare three usually
      employed techniques for collection of endometrial and inflammatory cells (guarded
      cotton swab, uterine lavage, and cytobrush) in chronically infertile mares.
      Twenty Standardbred mares were used. In each mare, samples for EC were collected,
      first by a cotton swab (DGS), then by a cytobrush (CB), and finally by low volume
      flush (LVF). The slides were stained using the Diff Quick stain. The following
      parameters were assessed for each tested technique: background content of the
      slides; quality of the cells harvested; total cellularity; neutrophils; ratio
      PMN/uterine epithelial cells; inflammatory cells; vaginal epithelium cells.
      Categorical variables were compared using contingency tables and Pearson Chi
      square tests, whereas continuous variables were compared using one-way analysis
      of variance (ANOVA); P<0.05 was considered significant. Samplings by DGS and CB
      resulted easy and quick to perform via a single operator in all cases. LVF was
      performed easily, but required the presence of 2-3 players and took more time.
      The background content of the slides prepared by DGS appeared proteinaceous,
      slides prepared by LVF appeared contaminated by red blood cells or debris,
      whereas slides prepared by CB appeared clear. All smears showed a good total
      cellularity. The CB yielded significantly more cells (P<0.0001) than DGS and LVF.
      The DGS produced significant more cells than LVF (P<0.0001). The DGS produced
      significantly more (P=0.003) intact cells than CB and LVF. Distorted cells were
      significantly (P=0.001) more frequent in smears by LVF. The CB harvested
      significantly (P=0.009) more fragmented cells. CB and LVF produced significantly
      (P<0.0001; P=0.02) more PMNs/HPF than DGS. In smears collected by LVF the
      proportion of PMNs/uterine epithelial cells was significantly (P=0.0062;
      P=0.0023) higher than in smears by CB and DGS. CB collected a significantly
      higher (P=0.0011) proportion of PMNs than DGS. Acute endometritis was diagnosed
      in 50% (10/20) of the mares by DGS cytological samples, 25% (5/20) by CB, and 75%
      (15/20) by LVF. Inflammatory cells other than PMN (lymphocytes, macrophages,
      eosinophils) were collected exclusively by CB method. Epithelial cells from the
      vagina were only detected in LVF slides. The agreement of the diagnosis of
      endometritis between the three techniques of collection and between the different
      criteria adopted to evaluate smears obtained with the same technique was poor
      (k<=0.3). In conclusion, results show that cytobrush and flush specimens were
      superior in all parameters to cotton swab smears. Even though the cytobrush
      technique requires specialized equipment, sample collection by this method was
      easier, more consistent, and quicker than the lavage method, indicating that the
      brush would be the preferred collection method for use on field in the mare. More
      studies are needed to establish criteria for interpretation of inflammation in
      the mare on cytobrush samples.

PMID- 21855981
TI  - Seasonal variation in reproductive physiological status in the Iberian ibex
      (Capra pyrenaica) and its relationship with sperm freezability.
AB  - The present work examines the relationship between seasonal changes in testicular
      function, accessory gland size, and horn growth in Iberian ibexes, as well as the
      relationship between these changes and the resistance of ibex spermatozoa to
      freezing-thawing. The size of the bulbourethral glands and seminal vesicles
      showed pronounced monthly variation (P < 0.001), which was correlated positively
      with the plasma testosterone concentration (P < 0.001) and scrotal circumference
      (P < 0.001). The size of the accessory sex glands peaked during the autumn.
      Overall, semen quality was markedly improved during autumn and winter. When horn
      growth was at a minimum during autumn and winter, semen quality and accessory
      gland size were all increased compared to in spring and summer. However,
      increased plasma testosterone levels in the autumn were strongly associated with
      reduced sperm freezability; thus, the cryosurvival of spermatozoa collected
      during the autumn was poorer than at other times of the year. In winter, however,
      when the plasma testosterone concentration fell to baseline, the negative effects
      of cryopreservation on the percentage of motile spermatozoa and on the integrity
      of the plasma membrane of frozen-thawed sperm cells were significantly less
      intense (P < 0.05). These findings show a clear relationship between the
      functional and morphological status of the different parts of the reproductive
      tract that optimises reproductive function during the breeding season in the ibex
      male. They also show that winter is the most suitable season for the collection
      and cryopreservation of ibex spermatozoa.

PMID- 21855982
TI  - Effect of leptin during in vitro maturation of prepubertal calf oocytes:
      embryonic development and relative mRNA abundances of genes involved in apoptosis
      and oocyte competence.
AB  - During the in vitro maturation of adult bovine oocytes, leptin has beneficial
      effects on blastocyst development, apoptosis and transcription levels of
      developmentally important genes. The present study analyzes the differential
      effects of leptin on prepubertal bovine oocytes and cumulus cells. Effects were
      determined of leptin treatment during oocyte maturation on their developmental
      capacity after fertilization (Exp. 1), incidence of apoptosis in cumulus oocyte
      complexes (COCs) (Exp. 2) or on relative mRNA abundances of genes in cumulus
      cells and oocytes (Exp. 3). COCs were matured in serum-free medium containing 1
      mg/mL polyvinyl alcohol and 0, 10, 100, or 1000 ng/mL leptin (L0, L10, L100, and
      L1000, respectively), or in medium supplemented with 10% fetal calf serum (FCS)
      as a positive control. Addition of leptin during oocyte maturation had no effect
      on cleavage rates after fertilization (FCS, 68.6%; L0, 62.9%; L10, 66.9%; L100,
      63.4%; L1000, 60.9%). Similarly, no significant differences in blastocyst rates
      were observed when oocytes were matured in the presence of L0 (8.4%), L10 (9.3%),
      L100 (6.7%), L1000 (8.2%), compared to control FCS (9.4%). In Experiment 2,
      maturation in the presence of 1000 ng/mL of leptin increased the proportion of
      TUNEL-positive cumulus cell (6.9%) with respect to those matured in the presence
      of FCS (4.96%), but not at the lower leptin doses. When relative mRNA abundances
      were examined for seven genes by qRT-PCR, five (TP53, BAX, DNMT3A, PGTS2 and
      LEPR) showed differences among groups. LEPR expression was significantly higher
      in the oocytes matured with FCS compared with the other groups and in those
      matured with PVA (L0) without leptin compared with the three groups of oocytes
      matured in the presence of leptin. In conclusion, the addition of leptin to the
      in vitro maturation medium used for prepubertal bovine oocytes does not increase
      the development potential of the oocytes or reduce the percentage of apoptosis in
      cumulus cells. Leptin blocks transcription of the leptin receptor (LEPR) probably
      reflecting selective, differential degradation by doses of leptin.

PMID- 21855983
TI  - Viability of ICSI oocytes after caffeine treatment and sperm membrane removal
      with Triton X-100 in pigs.
AB  - Non-adequate decondensation of injected sperm nucleus is one the main problems of
      intracytoplasmic sperm injection (ICSI) in porcine. With the aim of improving
      pronuclear formation, the effects on activation and embryo development rates of
      0.1% Triton X-100 (TX) sperm pre-treatment for membrane removal and/or 5 mM
      Caffeine (CAF) addition in oocyte manipulating and culture medium for 2 h after
      ICSI or artificial activation were studied. The effects of 4 different Ca(2+)
      concentrations contained in the injection medium on embryo development after sham
      injection were also analysed. In Experiment 1, no significant effect on cleavage
      or blastocyst rate was detected independently of Ca(2+) concentration contained
      in the injection medium. In Experiment 2, oocytes injected with TX pre-treated
      sperm showed a significant higher rate of male pronuclear formation in comparison
      with oocytes from control group (2PN; 54.1 vs 36.6%). However, no differences on
      in vitro embryo development, cleavage or blastocyst rates were observed. In
      Experiment 3, oocytes treated with CAF during and after micromanipulation and
      injected with sperm pre-treated with TX had a significantly lower oocyte
      activation rate than any other experimental groups (25.7 vs 56.3-66.3%). No
      differences were observed in cleavage rates among different experimental groups.
      However, the CAF group showed a higher blastocyst rate significantly different
      from TX+CAF group (12.0 vs 1.9%, respectively). In a second approach, the effect
      of electric field strengths and CAF treatments on oocyte activation was studied.
      In Experiment 4, oocytes submitted to 0.6 kV/cm showed significant higher
      activation rates than 1.2 kV/cm ones regardless of the caffeine treatment (83.7
      vs 55.9% and 75.7 vs 44.3%; in control and caffeine groups, respectively). No
      effect of caffeine treatment was observed in any experimental group. In
      conclusion, TX sperm treatment before ICSI without an additional activation
      procedure improved male pronuclear formation, but did not improve embryo
      development until blastocyst stage. No significant effect of caffeine was found
      when sperm was not treated with TX, although in membrane absence caffeine avoided
      oocyte activation and embryo development. Finally, caffeine had no effect on
      female pronuclear formation regardless of electric field strengths applied to the
      parthenogenetic activation.

PMID- 21855984
TI  - Terminologies for the pre-attachment bovine embryo.
AB  - There are numerous publications regarding bovine embryos, ranging from
      descriptions of their appearance and development to emerging techniques in the
      field of assisted reproductive technology (ART). Concurrently, several
      specialized terms have been developed to describe the bovine embryo. Many of
      these terms are simple, some are difficult to understand and use, and others are
      antiquated and may not be scientifically accurate. For example, use of terms such
      as syngamy, conception rate, implantation and embryo resorption should be
      revisited. This review presents a brief overview of current knowledge regarding
      the pre-attachment period of the bovine embryo and attempts to define the terms.
      In this process, conventional terminology is presented, and contemporary and
      novel terms are proposed from a biological perspective.

PMID- 21855985
TI  - Influence of progesterone on oocyte quality and embryo development in cows.
AB  - In cattle, the majority of embryo loss occurs very early during pregnancy
      (approximately Day 16), around or prior to maternal recognition of pregnancy. The
      actions of P4 in controlling LH pulsatility and ovarian follicular development
      may impinge negatively on oocyte quality. A considerable proportion of embryo
      loss may be attributable to inadequate circulating progesterone (P4)
      concentrations and the subsequent downstream consequences on endometrial gene
      expression and histotroph secretion into the uterine lumen. Conceptus growth and
      development require the action of P4 on the uterus to regulate endometrial
      function, including conceptus-maternal interactions, pregnancy recognition, and
      uterine receptivity for implantation. This review summarizes recent data
      highlighting the role of progesterone in determining oocyte quality and embryo
      development in cattle.

PMID- 21855986
TI  - Morpho-functional studies regarding the fertility prognosis of mares suffering
      from equine endometrosis.
AB  - The aim of the present study was to characterize the morpho-functional features
      of endometrosis in barren and foaling mares, using both conventional
      histopathological and immunohistochemical methods. Endometrial biopsy samples
      were collected during the physiological breeding season from 159 estrous,
      clinically healthy mares (mean age 12 years), and the quality and degree of
      endometrosis was histomorphologically defined. The mares were bred and those that
      foaled were put in the foaling group whereas those that did not foal were placed
      in the barren group. Foaling mares were then compared with barren mares. Sixty
      four percent (101/159) of uterine samples showed varying degrees of endometrosis
      and were used for this study. The sample population consisted of 51 barren and 50
      foaling mares suffering from endometrosis. Expression of steroid hormone
      receptors (estrogen receptor, progesterone receptor) and endometrial protein
      secretion patterns (uteroglobin [UG], uterocalin [UC], calbindin(D9k) [CAL],
      uteroferrin [UF]) was evaluated by immunohistochemistry (barren mares N = 51,
      foaling mares N = 31). In comparison with unaffected glands, fibrotic glands
      generally showed a cycle-asynchronous, partially patchy protein expression
      pattern which is interpreted as a sign of endometrial maldifferentiation within
      fibrotic areas. In barren mares (N = 51) more than half of biopsy samples (27/51)
      showed a destructive mostly moderate (20/27) type of endometrosis. In affected
      glands, staining for UG (17/21) was decreased (P < 0.001). Foaling mares (N = 50)
      frequently showed a mild, nondestructive endometrosis (35/50). Compared with
      barren mares, foaling mares had statistically (P < 0.05) more often a cycle
      synchronous or increased UG expression pattern within fibrotic glands. Obvious
      deviations of either UG or UC rarely occurred. Within fibrotic foci, UF often
      demonstrated a cycle-synchronous or more intense expression pattern in both
      foaling (28/31) and barren mares (41/51), compared with healthy glands. Mares of
      both groups showed a cycle-asynchronous staining for estrogen receptor and
      progesterone receptor in the stromal cells in areas of periglandular fibrosis and
      the glandular epithelia. These findings indicate that affected areas become
      independent of the uterine control mechanisms and exhibit specific
      differentiation dynamics. Immunohistochemical investigations showed that the
      secretory patterns differ between barren and foaling mares. The findings in this
      study should be considered as a useful addition to the "classical" Kenney
      categorization.

PMID- 21855987
TI  - Effect of methanol on mitochondrial organization in zebrafish (Danio rerio)
      ovarian follicles.
AB  - Successful cryopreservation is usually measured in terms of cell survival.
      However, there may also be more subtle effects within cells that survive.
      Previous studies on zebrafish have produced evidence of mitochondrial DNA (mtDNA)
      damage in cryopreserved embryonic blastomeres and, after exposure to
      cryoprotectants, alterations in mtDNA replication in embryos and decreased
      mitochondrial membrane potential, mtDNA and ATP production in ovarian follicles.
      This study shows that the decreased ATP levels previously observed in stage III
      zebrafish ovarian follicles exposed to >=3 M methanol persisted in those
      follicles that subsequently developed to stage IV. However, the decreased mtDNA
      levels were restored in those follicles. In order to determine whether
      mitochondrial distribution and/or their transport network was affected by the
      methanol exposure, immunocytochemistry analysis of tubulin and mitochondrial
      cytochrome c oxidase I (COX-I) was performed, along with phalloidin staining of
      polymerized actin. Neat arrangements of all proteins were observed in control
      follicles, with COX-I and tubulin being colocalized near granulosa cell nuclei,
      while actin formed hexagonal and/or polygonal structures nearer granulosa cell
      membranes and projected into the oocyte surface. Exposure to methanol (2 to 4 M)
      disrupted the COX-I and tubulin arrangements and the hexagonal and/or polygonal
      actin distribution and actin projections into the oocyte. These effects were
      still observed in those follicles that developed to stage IV, although the
      severity was reduced. In summary, the disruption to function and distribution of
      mitochondria in ovarian follicles exposed to >2 M methanol may be mediated via
      disruption of the mitochondrial transport system. Some recovery of this
      disruption may take place after methanol removal and subsequent follicle
      maturation.

PMID- 21855988
TI  - The effect of a single high dose of PGF2alpha administered to dairy cattle 3.5
      days after ovulation on luteal function, morphology, and follicular dynamics.
AB  - A single treatment with PGF2alpha is assumed to have no luteolytic effect on cows
      with corpora lutea < 5 days old. The objective of this study was to determine the
      effect of a single high dose of PGF2alpha administered to dairy cattle on the
      morphology and function of the early CL. The study followed a crossover design
      with a treatment cycle in which 50 mg of dinoprost were administered 3.5 days
      postovulation and a control untreated cycle. Ultrasound examination and blood
      samples were performed during the two consecutive cycles. Corpus luteum (CL)
      diameter, progesterone concentration, and follicular dynamics characteristics
      were compared between control and treated cycles. Two of nine cows (22%)
      developed full luteolysis. The remaining seven cows (78%) had partial luteolysis
      with a decrease (P < 0.05) in progesterone concentration and CL diameter for two
      and 12 days post-treatment, respectively. The interovulatory interval of treated
      cycles (19.7 +/- 2.4 days) was not different (P > 0.05) from that of controls
      (23.8 +/- 0.9 days). The transient reduction in progesterone of cows with partial
      luteolysis had no effect on the proportion of cows with two or three follicular
      waves, follicle growth rate, or preovulatory diameter (P > 0.05). Two cows
      developed ovarian cystic degeneration during the PGF2alpha-induced cycle. In
      conclusion, the treatment of cows with a high dose of PGF2alpha 3.5 days
      postovulation induced some degree of luteolysis in all treated cows. This
      resulted in partial luteolysis in 78% of treated animals and in full luteolysis
      in the remaining 22%.

PMID- 21855989
TI  - Expression of maturation genes and their receptors during in vitro maturation of
      sheep COCs in the presence and absence of somatic cells of cumulus origin.
AB  - The purpose of this study was to investigate the effects of somatic cells of
      cumulus origin (sCC) on gene expression and maturation of cumulus oocyte
      complexes (COCs) in vitro. Good quality (i.e., healthy-looking) isolated sheep
      COCs were randomly divided into two treatment groups: control (COC with no sCC)
      and coculture (COC with sCC). Nuclear maturation statuses of oocytes were
      assessed after 27 hours of in vitro culture. Moreover, the expression levels of
      growth differentiation factor 9 (GDF9), bone morphogenetic protein (BMP)15, BMP6,
      bone morphogenetic protein receptor II (BMPRII), activin like kinase 5 (ALK5)
      (transforming growth factor beta receptor 1: TGFbetaR1), ALK6 (BMPR1b), activin A
      receptor, type IIB (ActRIIB), and ALK3 (BMPR1a), as well as hyaluronan synthase 2
      (HAS2) and prostaglandin endoperoxide synthase 2 (Ptgs2) in the COCs were
      assessed in both treatment groups after 3 h and 27 h of culture. The results
      showed that the proportion of metaphase II (MII) stage oocytes was significantly
      higher in the coculture group compared with the controls (77.21%+/-1.17 vs.
      67.49%+/-1.80; P<0.05). The relative expressions of BMPRII, ALK6, and ActRIIB in
      control group and GDF9 and ActRIIB in coculture group showed significant
      differences during culture as assessed by real time polymerase chain reaction
      (P<0.05). The mean expression levels of BMPRII, ALK5, ALK6, and ActRIIB mRNA were
      decreased in the coculture group compared with those in the control group after
      27 h of culture (P<0.05). In conclusion, we propose that in vitro maturation of
      sheep COCs alone disrupted the normal gene expression levels of both TGFbeta
      ligands and receptors, and also reduced the maturation rate. Coculture with sCC
      enhanced the maturation rate of oocytes concomitantly with reduced gene
      expression levels of a number of TGFbeta ligands and receptors.

PMID- 21855990
TI  - Long-term and transgenerational effects of in vitro culture on mouse embryos.
AB  - The mouse is a convenient model to analyze the impact of in vitro culture (IVC)
      on the long-term health and physiology of the offspring, and the possible
      inheritance of these altered phenotypes. The preimplantation period of mammalian
      development has been identified as an early 'developmental window' during which
      environmental conditions may influence the pattern of future growth and
      physiology. Suboptimal culture media can cause severe alterations in mRNA
      expression in the embryo, which are associated with embryo quality reduction. In
      addition, the embryonic epigenetic reprogramming may also be severely affected by
      IVC, modifying epigenetic marks particularly in imprinted genes and
      epigenetically sensitive alleles. These altered epigenetic marks can persist
      after birth, resulting in adult health problems such as obesity, increased
      anxiety and memory deficits. Furthermore, some epigenetic modifications have been
      found to be transmitted to the offspring (epigenetic transgenerational
      inheritance), thereby providing a suitable model to asses risks of cross
      generational effects of perturbing early embryo development. This review will
      highlight how preimplantation environment changes can not only affect
      developmental processes taking place at that time, but can also have an impact
      further, affecting offspring health and physiology; and how they may be
      transmitted to the next generation. We will also analyze the emerging role of
      epigenetics as a mechanistic link between the early environment and the later
      phenotype of the developing organism.

PMID- 21855991
TI  - Gestational losses in a rabbit line selected for growth rate.
AB  - Prenatal death can occur due to several genetic and environmental factors which
      alter normal embryo development, maternal environment to support normal
      fertilisation, development of embryos, placenta and foetus, or affect the
      necessary relationship between embryo and endometrium. The aim of this work was
      to study gestational losses and progesterone, 17 beta-estradiol and IGF I serum
      levels in a rabbit line selected for growth rate (paternal line). In this study,
      a maternal line well characterised in previous studies was used as a reference
      line. A total of 211 laparoscopies were carried out, and the number of corpora
      lutea and implanted embryos at 12th days, total born and live born were recorded
      per female. To analyse the endocrine levels, blood serum was collected from 54
      females with implanted embryos at 12th and 24th day of gestation (27 from each
      line). The paternal line showed the lowest ovulation frequency, number of
      implanted embryos, total born and live born (0.70, 11.3, 7.4, and 6.4 vs 0.86,
      12.8, 11.1 and 10.6 for maternal line, respectively) and consequently, the
      highest implantation, gestational, foetal and perinatal losses (0.31, 0.60, 0.40,
      and 0.15, respectively). Progesterone serum levels at 12th days of gestation were
      similar between lines; however, progesterone serum level at 24th day of gestation
      was significantly lower in the paternal line (4.8 vs 8.2 ng/mL). Serum levels of
      17beta-estradiol and IGF-I at 12th days of gestation were different between lines
      (14.6 vs 26.5 pg/mL, 237 vs 149 ng/mL for paternal and maternal lines
      respectively). These higher gestational losses of the paternal line could be
      explained by differences in 17 beta-estradiol level at 12th days of gestation and
      the possible effect on low progesterone serum levels at 24th days of gestation.
      Further studies in steroid production and bioavailability have to be done during
      oestrus and pregnancy related with metabolic activity of this line.

PMID- 21855992
TI  - Freezing-thawing induces alterations in histone H1-DNA binding and the breaking
      of protein-DNA disulfide bonds in boar sperm.
AB  - The main aim of this work is to gain insight into the mechanisms by which
      freezing-thawing alters the nucleoprotein structure of boar sperm. For this
      purpose, the freezing-thawing-related changes of structure and location of
      histones-DNA domains in the boar sperm head were analyzed through Western blot
      and immunocytochemistry. Afterwards, it was analyzed whether freezing-thawing
      induced changes in tyrosine phosphorylation levels of both protamine 1 and
      histone H1, through Western blot analyses in samples previously subjected to
      immunoprecipitation. This analysis was completed with the determination of the
      changes induced by freezing-thawing on the overall levels of sperm-head disulfide
      bonds through analysis of free-cysteine radicals levels. Freezing-thawing induced
      significant changes in the histones-DNA structures, which were manifested in the
      appearance of a freezing-thawing-linked histone H1-DNA aggregate of about a 35
      kDa band and in the spreading of histone H1-positive markings from the caudal
      area of the sperm head to more cranial zones. Freezing-thawing did not have any
      significant effect on the tyrosine phosphorylation levels of either protamine 1
      or histone H1. However, thawed samples showed a significant (P < 0.05) increase
      in the free cysteine radical content (from 3.1 +/- 0.5 nmol/MUg protein in fresh
      samples to 6.7 +/- 0.8 nmol/MUg protein). In summary, our results suggest that
      freezing-thawing causes significant alterations in the nucleoprotein structure of
      boar sperm head by mechanism/s linked with the rupture of disulfide bonds among
      the DNA. These mechanisms seem to be unspecific, affecting both the protamines
      DNA unions and the histones-DNA bonds in a similar way. Furthermore, results
      suggest that the boar-sperm nuclear structure is heterogeneous suggesting the
      existence of a zonated pattern, differing in their total DNA density and the
      compactness of the precise nucleoprotein structures present in each zone.

PMID- 21855993
TI  - Measles.
AB  - Measles is a highly contagious disease caused by measles virus and is one of the
      most devastating infectious diseases of man--measles was responsible for millions
      of deaths annually worldwide before the introduction of the measles vaccines.
      Remarkable progress in reducing the number of people dying from measles has been
      made through measles vaccination, with an estimated 164,000 deaths attributed to
      measles in 2008. This achievement attests to the enormous importance of measles
      vaccination to public health. However, this progress is threatened by failure to
      maintain high levels of measles vaccine coverage. Recent measles outbreaks in sub
      Saharan Africa, Europe, and the USA show the ease with which measles virus can re
      enter communities if high levels of population immunity are not sustained. The
      major challenges for continued measles control and eventual eradication will be
      logistical, financial, and the garnering of sufficient political will. These
      challenges need to be met to ensure that future generations of children do not
      die of measles.

PMID- 21855994
TI  - Effects of barium and cadmium on the population development of the marine
      nematode Rhabditis (Pellioditis) marina.
AB  - Offshore oil and gas drilling often involves the use of fluids containing barium
      and traces of other heavy metals. These may affect the environment, but
      information on their toxicity to benthic biota remains scant. Here, we present
      results of a 10-day bioassay with the marine nematode Rhabditis (Pellioditis)
      marina at different loads of barium (0-10 ,000 ppm nominal concentrations) and
      cadmium (0-12 ppm) in the range of concentrations reported from drilling-impacted
      sediments. Barium did not affect the fitness and population development of R.
      (P.) marina at concentrations up to 300 ppm, but did cause a decrease in
      population abundance and an increase in development time from concentrations of
      400-2000 ppm onwards. Increased mortality occurred at 4800 ppm Ba. For cadmium,
      LOEC and EC50 values for total population abundance were 2.95 and 8.82 ppm,
      respectively. Cd concentrations as low as 2.40 to 2.68 caused a decrease in the
      abundance of adult nematodes, indicating that assays covering more generations
      would likely demonstrate yet more pronounced population-level effects. Our
      results indicate that oil and gas drilling activities may potentially have
      important implications for the meiobenthos through the toxicity of barium and
      associated metals like cadmium.

PMID- 21855995
TI  - The use of nitroxide radical-containing nanoparticles coupled with piperine to
      protect neuroblastoma SH-SY5Y cells from Abeta-induced oxidative stress.
AB  - The antioxidant effect and potential mechanism of nitroxide radical-containing
      nanoparticles (RNPs) coupled with piperine (PI) were investigated in human
      neuroblastoma SH-SY5Y cells. The effects of RNP/PI on SH-SY5Y cell lines was
      determined by WST assay for cell viability, nitroblue tetrazolium and deoxyribose
      assay for reactive oxygen species generation, ELISA assay for reactive oxygen
      species products and apoptotic cell death, and biochemical techniques for
      catalase and glutathione peroxidase activity. The RNP/PI significantly reduced
      the reactive oxygen species level and reactive oxygen species products compared
      with those of cells treated with RNPs alone. The RNP/PI treatment enhanced
      catalase and glutathione peroxidase activity. The combination of RNP/PI has been
      found to have an augmented antioxidant effect on an Alzheimer's model in vitro.
      The mechanism of the protective effect of this combination therapy was correlated
      in this study with its ability to reduce the generation of reactive oxygen
      species and prevent apoptosis via scavenging enzyme action pathways.

PMID- 21855996
TI  - Anagrelide and cardiovascular events. Much ado about nothing?

PMID- 21855997
TI  - Donor Tregs suppress the good with the bad after allogeneic BMT.

PMID- 21855998
TI  - Organizational climate, services, and outcomes in child welfare systems.
AB  - OBJECTIVE: This study examines the association of organizational climate,
      casework services, and youth outcomes in child welfare systems. Building on
      preliminary findings linking organizational climate to youth outcomes over a 3
      year follow-up period, the current study extends the follow-up period to 7 years
      and tests main, moderating and mediating effects of organizational climate and
      casework services on outcomes. METHODS: The study applies hierarchical linear
      models (HLMs) analyses to all 5 waves of the National Survey of Child and
      Adolescent Well-being (NSCAW) with a US nationwide sample of 1,678 maltreated
      youth aged 4-16 years and 1,696 caseworkers from 88 child welfare systems.
      Organizational climate is assessed on 2 dimensions, Engagement and Stress, with
      scales from the well established measure, Organizational Social Context (OSC);
      youth outcomes are measured as problems in psychosocial functioning with the
      Child Behavior Checklist (CBCL); and casework services are assessed with original
      scales developed for the study and completed by the maltreated youths' primary
      caregivers and caseworkers. RESULTS: Maltreated youth served by child welfare
      systems with more engaged organizational climates have significantly better
      outcomes. Moreover, the quantity and quality of casework services neither mediate
      nor interact with the effects of organizational climate on youth outcomes.
      CONCLUSIONS: Organizational climate is associated with youth outcomes in child
      welfare systems, but a better understanding is needed of the mechanisms that link
      organizational climate to outcomes. In addition, there is a need for evidence
      based organizational interventions that can improve the organizational climates
      and effectiveness of child welfare systems.

PMID- 21855999
TI  - Combined exposure of Japanese quails to cyanotoxins, Newcastle virus and lead:
      oxidative stress responses.
AB  - Wild birds are continually exposed to many anthropogenic and natural stressors in
      their habitats. Over the last decades, mass mortalities of wild birds constitute
      a serious problem and may possibly have more causations such as natural toxins
      including cyanotoxins, parasitic diseases, industrial chemicals and other
      anthropogenic contaminants. This study brings new knowledge on the effects of
      controlled exposure to multiple stressors in birds. The aim was to test the
      hypothesis that influence of cyanobacterial biomass, lead and antigenic load may
      combine to enhance the effects on birds, including modulation of antioxidative
      and detoxification responses. Eight treatment groups of model species Japanese
      quail (Coturnix coturnix japonica) were exposed to various combinations of these
      stressors. The parameters of detoxification and oxidative stress were studied in
      liver and heart after 30 days of exposure. The antioxidative enzymatic defense in
      birds seems to be activated quite efficiently, which was documented by the
      elevated levels and activities of antioxidative and detoxification compounds and
      by the low incidence of damage to lipid membranes. The greatest modulations of
      glutathione level and activities of glutathione-S-transferase, glutathione
      peroxidase, glutathione reductase, superoxide dismutase, catalase and lipid
      peroxidation were shown mostly in the groups with combined multiple exposures.
      The results indicate that the antioxidative system plays an important role in the
      protective response of the tissues to applied stressors and that its greater
      induction helps to protect the birds from more serious damage. Most significant
      changes of these "defense" parameters in case of multiple stressors suggest
      activation of this universal mechanism in situation with complex exposure and its
      crucial role in protection of the bird health in the environment.

PMID- 21856000
TI  - A systematic review of patient-reported and economic outcomes: value to
      stakeholders in the decision-making process in patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: The need for an approach to measuring health results that
      incorporates patients' and payers' perspectives has generated a wide range of
      health care outcomes (HCOs), but it is yet unknown whether these HCOs are
      appropriate or valid for the health care decision-making process. OBJECTIVE: The
      goal of this study was to assess HCOs, patient-reported outcomes (PROs), and
      economic outcomes in terms of validity and appropriateness to health care
      decision making in type 2 diabetes mellitus (T2DM). METHODS: This systematic
      review of studies published between January 1, 1996, and November 1, 2010,
      comprised an electronic literature search of MEDLINE and Centre for Reviews and
      Dissemination databases. Studies included were clinical trials, observational
      studies, economic analyses, and studies on the development and validation of HCOs
      in T2DM in the adult population. HCOs were assessed and classified according to
      their relevance for decision makers in terms of feasibility for routine use,
      validity, sensitivity, reliability, understanding, and scope. RESULTS: Two
      independent reviewers screened 4497 citations. Of these, 281 potentially eligible
      full articles were retrieved, and 185 met the inclusion criteria. A total of 121
      HCOs in T2DM were identified: 80 (66.1%) PROs and 41 (33.9%) economic outcomes.
      Only 44.6% of the outcomes assessed were appropriate and valid for health care
      decision making. Greater deficiencies in evidence were found for PROs (61.3%),
      followed by economic outcomes (43.9%). CONCLUSIONS: A large number of HCOs are
      being used in the health care decision-making process, but a significant
      proportion of these new outcomes have not been properly validated. Despite the
      fact that appropriate measures will depend on the specific needs of the decision
      makers, researchers need to use HCOs for which evidence of quality and
      appropriateness is available.

PMID- 21856001
TI  - Intravenous, oral, and the combination of intravenous and oral ramosetron for the
      prevention of nausea and vomiting after laparoscopic cholecystectomy: a
      randomized, double-blind, controlled trial.
AB  - BACKGROUND: Patients undergoing general anesthesia for laparoscopic
      cholecystectomy have a high risk of postoperative nausea and vomiting (PONV) with
      incidences up to 75%. Ramosetron, a serotonin subtype 3 (5-HT(3)) antagonist, has
      been shown to be effective as an antiemetic after chemotherapy and surgery.
      Consensus guidelines recommend a combination of antiemetic therapies in high-risk
      groups. Until now, no published data have been available on the use of
      combination oral plus intravenous ramosetron. OBJECTIVE: The goal of this
      prospective, randomized, double-blind study was to compare the efficacy and
      tolerability of intravenous, oral, and the combination of oral and intravenous
      ramosetron for PONV prophylaxis in patients undergoing laparoscopic
      cholecystectomy. METHODS: Patients scheduled for laparoscopic cholecystectomy
      were double-randomly allocated to 1 of 3 groups. Patients were randomly allocated
      to receive either 0.3 mg of intravenous ramosetron (group A), 0.1 mg of oral
      ramosetron (group B), or the combination of 0.1 mg of oral ramosetron and 0.3 mg
      of intravenous ramosetron (group C). All patients received standardized balanced
      anesthesia with desflurane and remifentanil. Postoperative nausea, retching,
      vomiting, pain, and adverse effects were assessed at 0 to 2, 2 to 24, and 24 to
      48 hours after surgery. RESULTS: A total of 124 Korean patients (67 women, 57
      men; age range, 25-65 years) were randomized to 1 of 3 study groups (42 in group
      A [mean age, 49.8 years], 41 in group B [mean age, 47.4 years], and 41 in group C
      [mean age, 48.9 years]). No statistical differences were observed among the 3
      groups with regard to patient characteristics and information on surgery and
      anesthesia. During postoperative period 0 to 2 hours, complete response occurred
      in 31 (74%) patients in group A, 27 (66%) in group B, and 37 (90%) in group C.
      During the postoperative period of 2 to 24 hours, complete response was observed
      in 36 (86%), 33 (80%), and 40 (98%) patients in groups A, B, and C, respectively;
      there was a statistically significant difference in group C compared with group A
      or group B. During the postoperative period of 0 to 48 hours, incidences of
      rescue antiemetic use were 13 (31%), 14 (34%), and 3 (7%) in groups A, B and C,
      respectively. Common adverse effects (headache, dizziness, and drowsiness) were
      observed, but there was no significant difference in the incidences of adverse
      effects among the 3 groups (P > 0.05). CONCLUSIONS: The combination of 0.1-mg
      oral and 0.3-mg intravenous ramosetron was more effective than either 0.3-mg
      intravenous ramosetron or 0.1-mg oral ramosetron alone for the prophylaxis of
      nausea and vomiting after laparoscopic cholecystectomy during the first 24 hours
      after surgery. In addition, differences did not reach the level of statistical
      significance between 0.1 mg of oral ramosetron and 0.3 mg of intravenous
      ramosetron for the prevention of PONV in this patient population. Oral,
      intravenous, and combined oral and intravenous ramosetron appears well tolerated
      in the population studied. ClinicalTrials.gov identifier: NCT 01041183.

PMID- 21856002
TI  - No evidence of selenosis from a selenium-rich diet in the Brazilian Amazon.
AB  - Selenium (Se) is an essential element and a well-known anti-oxidant. In the Lower
      Tapajos River region of the Brazilian Amazon, biomarkers of Se range from normal
      to very high. The local traditional diet includes important Se sources such as
      Brazil nuts, chicken, game meat and certain fish species. Some studies have
      reported alterations in keratin structure, gastrointestinal problems and
      paresthesia in populations with high Se intake. The objective of the present
      study was to evaluate cutaneous and garlic odor of the breath signs and sentinel
      symptoms of Se toxicity (selenosis) in relation to Se status in communities along
      the Tapajos River. Participants (N=448), aged 15-87 years, were recruited from 12
      communities. Se concentrations were measured in blood (B-Se) and plasma (P-Se) by
      ICP-MS. A nurse performed an examination of the hair, nails, skin and breath for
      signs of Se toxicity. Interview-administered questionnaires were used to collect
      information on socio-demographics, medical history and possible symptoms of Se
      toxicity. In this population, the median levels of B-Se and P-Se were 228.4 MUg/L
      (range 103.3-1500.2 MUg/L) and 134.8 MUg/L (range 53.6-913.2 MUg/L) respectively.
      Although B-Se and P-Se surpassed concentrations considered toxic (B-Se: 1000
      MUg/L (U.S. EPA, 2002)), no dermal or breath signs or symptoms of Se toxicity
      were associated with the biomarkers of Se status. In the present study
      population, where Se intake is mostly from traditional diet, there is no evidence
      of selenosis. These findings support the need to re-assess Se toxicity
      considering factors such as the chemical form of Se exposure, route of exposure
      (inhaled versus ingested), co-exposures to toxic elements such as mercury.
      Considering the current food transition towards a western diet in the Amazon,
      further studies should address the possible association between high Se status
      and cardiometabolic health in this study population.

PMID- 21856003
TI  - Three novel Anas platyrhynchos avian beta-defensins, upregulated by duck
      hepatitis virus, with antibacterial and antiviral activities.
AB  - Three novel Anas platyrhynchos avian beta-defensins (Apl_AvBDs), Apl_AvBD4, 7 and
      12, were identified successfully and characterized in tissues from Peking ducks
      in the present study. The cDNA fragment of Apl_AvBD4 contained 171 bp, and
      encoded 56 amino acids. The complete nucleotide sequences of Apl_AvBD7 and 12
      contained 204 bp and 198 bp open reading frames, which encoded 67 and 65 amino
      acids, respectively. Both recombinant and synthetic forms of the three Apl_AvBDs
      showed antibacterial activity against most of the bacteria investigated,
      including Gram-negative and Gram-positive bacteria, except for Salmonella
      choleraesuis. In addition, the antibacterial activity of all the three Apl_AvBDs
      decreased significantly in 150 mM NaCl. Significant antiviral activity of the
      three Apl_AvBDs was shown against duck hepatitis virus (DHV). However, none of
      the Apl_AvBDs showed significant hemolytic activity. Additionally, the
      expressions of the three Apl_AvBDs in response to DHV infection was highly
      variable, and significant upregulation of Apl_AvBD7 in liver was found in
      response to infection at different time points. Expression of Apl_AvBD4 in
      thymus, and of Apl_AvBD7 in bone marrow was induced in a time-dependent fashion
      by DHV infection. In contrast, expression of Apl_AvBD12 was found to be
      significantly decreased, and was hard to detect in cecal tonsil, spleen, bursa of
      Fabricius, and thymus of ducks at some time points after DHV infection. The
      present results demonstrate that Apl_AvBDs play vital roles in the immune
      response of ducks against bacterial and viral pathogens.

PMID- 21856004
TI  - The role of higher-order protein structure in supporting binding by heteroclitic
      monoclonal antibodies: the monoclonal antibody KIM185 to CD18 also binds C4
      binding protein.
AB  - Heteroclitic monoclonal antibodies are characterized by the ability to bind
      multiple epitopes with little or no similarity. Such antibodies have been
      reported earlier, but insight into to the molecular basis of this propensity is
      limited. Here we report that the KIM185 antibody to human CD18 reacts with the
      plasma protein C4b-binding protein (C4BP). This was revealed during affinity
      purification procedures where human serum was incubated with surfaces coated with
      monoclonal antibodies to CD18. Other monoclonal antibodies to CD18 (KIM127 and
      TS1/18) showed no such interaction with C4BP. We constructed a sandwich-type time
      resolved immunofluorometric assay using KIM185 both as capture and developing
      antibody. By use of proteolytic fragments of KIM185 and recombinant deletion
      mutants of C4BP the interaction sites were mapped to the variable region of
      KIM185 and the oligomerization domain of C4BP, respectively. C4BP is a large
      oligomeric plasma protein that binds activated complement factor C4b and other
      endogenous ligands as well as microorganisms. By use of the recent
      crystallographic data on the structure of CD11c/CD18 and prediction of the
      secondary structure of the C4BP oligomerization domain, we show that epitopes
      bound by KIM185 in these proteins are unlikely to share any major structural
      similarity. However, both antigens may form oligomers that would enable avid
      binding by the antibody. Our report points to the astonishing ability of
      heteroclitic antibodies to accommodate the binding of multiple proteins with no
      or little structural similarity within the confined space of the variable
      regions.

PMID- 21856005
TI  - Maspin expression is regulated by the non-canonical NF-kappaB subunit in androgen
      insensitive prostate cancer cell lines.
AB  - Dysregulation of Maspin expression and constitutive activation of NF-kappaB
      subunits are important events in tumorigenesis of prostate cancer. Recent finding
      points that RelB, which contributes to the alternative NF-kappaB activity,
      interferes with carcinogenesis in the prostate. We report here, that both the
      classical and the alternative NF-kappaB activities are constitutively present in
      androgen-insensitive human prostate cancer cells. Maspin and RelB expression is
      correlated negatively in prostate cancer tissues at the later stage. TNF-alpha
      signaling triggers the nuclear accumulation of RelB and the concomitant reduction
      of Maspin expression in a time-dependent manner. In addition, the proteasome
      inhibitor-induced Maspin expression is accompanied by the reduction of RelB
      expression. A successful depletion of RelB expression, but not RelA expression,
      induces Maspin expression. RelB-deficiency abrogates the proteasome inhibitor
      induced Maspin expression. Moreover, we demonstrate that the enforced expression
      of RelB protein in prostate cancer cells inhibits Maspin expression. We propose
      that RelB is an essential molecule controlling the endogenous and the proteasome
      inhibitor-induced Maspin expression. Developing a RelB-targeted therapeutic
      intervention, which might be coupled with the induction of a tumor suppressor
      Maspin, is valuable in treating advanced, metastatic prostate cancer.

PMID- 21856006
TI  - Ophthalmic antibiotic use and multidrug-resistant staphylococcus epidermidis: a
      controlled, longitudinal study.
AB  - PURPOSE: To analyze the emergence of multidrug-resistant Staphylococcus
      epidermidis after repeated conjunctival exposure to topical macrolide or
      fluoroquinolone antibiotics. DESIGN: Prospective, controlled, longitudinal study
      with 1-year follow-up. PARTICIPANTS: Forty-eight eyes of 24 patients undergoing
      serial unilateral intravitreal (IVT) injections for choroidal neovascularization.
      METHODS: Subjects received 4 consecutive monthly unilateral IVT injections and
      then were treated as needed. Each subject was assigned randomly to 1 of 4
      antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin
      0.3%) and used only their assigned antibiotic after each injection. Conjunctival
      culture specimens of the treated and untreated fellow eye (control) were obtained
      at baseline and after each injection. All bacterial isolates were tested for
      antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc
      diffusion technique. MAIN OUTCOME MEASURES: Antibiotic susceptibility patterns
      and multidrug resistance of S. epidermidis. RESULTS: After 4 consecutive
      treatments, a total of 58 isolates of S. epidermidis each were isolated from
      control and treated eyes. Resistance to 3 or more antibiotics was present in 69%
      of S. epidermidis isolated from control eyes compared with 90% from treated eyes
      (P<0.02). A total of 46 and 38 isolates of S. epidermidis were cultured from
      control and treated eyes, respectively, from the fifth until the final injection.
      Resistance to 5 or more antibiotics was present in 48% of control eyes compared
      with 71% of treated eyes (P<0.05). In a significant number of fluoroquinolone
      treated eyes, S. epidermidis developed resistance to third-generation (P<0.01)
      and fourth-generation (P<0.01) fluoroquinolones compared with control eyes. In
      addition, these organisms developed resistance to trimethoprim/sulfamethoxazole
      (P<0.01), gentamicin (P<0.03), and clindamycin (P<0.05). Similarly, a significant
      number of azithromycin-treated eyes developed S. epidermidis resistant to
      macrolides (P<0.01) compared with control eyes and also developed increased
      resistance to trimethoprim/sulfamethoxazole (P<0.02) and doxycycline (P<0.01).
      CONCLUSIONS: Conjunctival S. epidermidis repeatedly exposed to fluoroquinolone or
      azithromycin antibiotics rapidly develop resistance. Coresistance to other
      antibiotics also was observed. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 21856007
TI  - The Bruckner transillumination test: limited detection of small-angle esotropia.
AB  - OBJECTIVE: To evaluate the sensitivity of the Bruckner test in detecting
      esotropia of 2 degrees  to 10 degrees  by interocular asymmetry of the red fundus
      reflex. DESIGN: Single-blinded evaluation of the diagnostic test. PARTICIPANTS:
      Five blinded observers and 20 isometropic orthotropes. TESTING: Set-up 1 included
      monocular evaluation of the Bruckner reflex test for each eye of 10 subjects. The
      subjects alternated fixation between an ophthalmoscope light and an eccentric
      target (2.5 degrees , 5 degrees , 7.5 degrees , and 10 degrees ). Set-up 2
      comprised simulation of esotropia of 2 degrees  to 5 degrees , 7.5 degrees , and
      10 degrees  by base-in prisms placed in front of both eyes of 20 subjects. The
      subjects fixated with either their right or left eye. As a control experiment,
      0.5 degrees  base-in prisms were used. MAIN OUTCOME MEASURES: Set-up 1 tested the
      sensitivity in detecting a change in reflex between central and eccentric retinal
      illumination. Set-up 2 tested the sensitivity and specificity in detecting
      asymmetry of the Bruckner reflex between the 2 eyes as a dimming of the reflex of
      the fixating eye in a 2 degrees  to 10 degrees  simulated esotropia. RESULTS: In
      set-up 1, fixation of the ophthalmoscope light owing to foveal dimming was
      discriminated from fixation of the eccentric target in 98.2% of the trials,
      regardless of target eccentricity. In set-up 2, esotropia of 2 degrees  to 5
      degrees  was detected in 62% of 100 trials by red reflex asymmetry. Dimming of
      the reflex in the fixating eye was found in 48% of 100 trials. Esotropia of 7.5
      degrees  and 10 degrees  was detected in 85% and 97% of the trials, respectively.
      Dimming in the fixating eye was present in 75% and 86% of the trials,
      respectively. Thirty-six percent of the 300 control tests were false-positives.
      CONCLUSIONS: When the eccentric fundus reflex was compared with the central
      reflex in the same eye, dimming owing to central fixation of the ophthalmoscope
      was reliably detected. However, comparison of the eccentric red reflex in the
      strabismic eye with the central reflex in the fixating eye showed that the
      Bruckner red reflex test was not suitable for detecting small angles of squint.
      FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest
      in any of the materials discussed in this article.

PMID- 21856008
TI  - Comparison of surgical outcomes between canaloplasty and trabeculectomy at 12
      months' follow-up.
AB  - PURPOSE: To compare operative outcomes of patients after canaloplasty and
      trabeculectomy through 12 months' follow-up. DESIGN: Retrospective,
      nonrandomized, comparative case series. PARTICIPANTS: We included 33 eyes of 33
      patients who underwent canaloplasty and 46 eyes of 46 patients who underwent
      trabeculectomy with 12 months' of postoperative follow-up. METHODS: Patients with
      open-angle glaucoma who underwent either canaloplasty or trabeculectomy with
      mitomycin C to control the intraocular pressure (IOP) between January 2007 and
      December 2008 were included. All surgeries were performed by a single surgeon
      (R.S.A.). MAIN OUTCOME MEASURES: Change in IOP, visual acuity (VA), postoperative
      medications, failure based on IOP (>18 or <4 mmHg at 1 year) or second operative
      procedure (any eye requiring reoperation) and complication rates at 12 months.
      RESULTS: There were no differences in demographics, previous surgery, or
      preoperative and postoperative VA between the groups. The mean percentage
      reduction in IOP from preoperative values at 12 months after surgery was 32% (+/-
      22%) for the canaloplasty group compared with 43% (+/- 28%) for the
      trabeculectomy group (P = 0.072, Student t test). The median reduction in the
      number of medications at 12 months' follow-up was 3 in the trabeculectomy group
      and 2 in the canaloplasty group (P = 0.064). A higher percentage of patients
      treated with canaloplasty than trabeculectomy (36% vs. 20%) required
      postoperative medications, although this did not attain significance (P = 0.12).
      Failure based on IOP (IOP >18 or <4 mmHg at 12 months) was 12.1% (4/33 patients)
      for the canaloplasty group and 4.3% (2/46 patients) for the trabeculectomy group
      (P = 0.23, Fisher exact test). There was no difference in surgical failure rates
      between the canaloplasty (n = 5; 15%) and trabeculectomy (n = 5; 11%) groups (P =
      0.74). CONCLUSIONS: Canaloplasty and trabeculectomy both achieved significant
      reduction in IOP at 12 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 21856009
TI  - The relationship between glaucoma medication adherence, eye drop technique, and
      visual field defect severity.
AB  - OBJECTIVE: The purpose of the study was to examine (1) how patient adherence and
      eye drop technique were associated with visual field defect severity and (2) how
      general glaucoma adherence self-efficacy and eye drop technique self-efficacy
      were related to visual field defect severity. DESIGN: Cross-sectional study
      conducted at a single private practice site. PARTICIPANTS: Patients using eye
      drops for their glaucoma. METHODS: Subject adherence to glaucoma medications
      through Medication Events Monitoring System (MEMS) devices were measured, and eye
      drop instillation technique was assessed by video recording. General glaucoma
      medication adherence self-efficacy was measured using a 10-item scale, and eye
      drop technique self-efficacy was measured using a 6-item scale. Multivariate
      logistic regression was used to analyze the data. MAIN OUTCOME MEASURES: Visual
      field defect severity. RESULTS: Patients who were less than 80% adherent
      according to the MEMS devices were significantly more likely to have worse defect
      severity. Patients with lower scores on the general glaucoma medication adherence
      self-efficacy scale also were significantly more likely to have worse defect
      severity. Eye drop technique and eye drop technique self-efficacy were not
      related significantly to visual field defect severity. CONCLUSIONS: Eye care
      providers need to assess patient adherence and to work with those patients with
      poor adherence to find ways to improve their ability and self-efficacy in using
      their glaucoma medications. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 21856010
TI  - Risk factors for astigmatism in preschool children: the multi-ethnic pediatric
      eye disease and Baltimore pediatric eye disease studies.
AB  - OBJECTIVE: To evaluate risk factors for astigmatism in a population-based sample
      of preschool children. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: Population-based samples of 9970 children ages 6 to 72 months from
      Los Angeles County, California, and Baltimore, Maryland. METHODS: A cross
      sectional study of children participating in the Multiethnic Pediatric Eye
      Disease Study and the Baltimore Eye Disease Study was completed. Data were
      obtained by clinical examination or by in-person interview. Odds ratios and 95%
      confidence intervals (CI) were calculated to evaluate potential associations
      between clinical, behavioral, or demographic factors and astigmatism. MAIN
      OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with
      astigmatism. RESULTS: Participants with myopia (<=-1.0 diopters) were 4.6 times
      as likely to have astigmatism (95% CI, 3.56-5.96) than those without refractive
      error, whereas participants with hyperopia (>=+2.00 diopters) were 1.6 times as
      likely (95% CI, 1.39-1.94). Children 6 to <12 months of age were approximately 3
      times as likely to have astigmatism than children 5 to 6 years of age (95% CI,
      2.28-3.73). Both Hispanic (OR, 2.38) and African-American (OR, 1.47) children
      were as likely to have astigmatism than non-Hispanic white children. Furthermore,
      children whose mothers smoked during pregnancy were 1.46 times (95% CI, 1.14
      1.87) as likely to have astigmatism than children whose mothers did not smoke.
      CONCLUSIONS: In addition to infancy, Hispanic and African-American race/ethnicity
      and correctable/modifiable risk factors such as myopia, hyperopia, and maternal
      smoking during pregnancy are associated with a higher risk of having astigmatism.
      Although the prevalence of smoking during pregnancy is typically low, this
      association may suggest etiologic pathways for future investigation. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 21856011
TI  - Determination of valid benchmarks for outcome indicators in cataract surgery: a
      multicenter, prospective cohort trial.
AB  - OBJECTIVE: To evaluate a systematic approach to derive valid benchmarks for 2
      outcome indicators intended to ascertain quality in cataract surgery and to
      propose benchmark levels drawn from the study results. DESIGN: Prospective,
      multicenter cohort trial. PARTICIPANTS: A total of 1685 patients (206-239 eyes
      per trial site) were recruited consecutively at 7 study sites. The patients
      featured age-related cataracts and were undergoing unilateral cataract surgery in
      the period between January 2007 and August 2008. METHODS: Only patients with
      uncomplicated age-related cataracts were included. Cataract surgery was performed
      by phacoemulsification. The SN60AT (Alcon, Inc., Fort Worth, TX) intraocular lens
      (IOL) was used as a study lens. The IOL power was calculated using the SRK-T
      formula with a standardized A constant. Biometry was performed with the IOL
      Master (Carl Zeiss Meditex, Jena, Germany). Only highly experienced senior
      surgeons were involved. MAIN OUTCOME MEASURES: The outcome indicators 1 month and
      3 months after surgery were the respective achievement of: (1) maximum absolute
      deviation of 0.5 diopter (D) between target refraction and postoperative
      spherical equivalent (primary end point, refractive accuracy); (2) best-corrected
      visual acuity of at least 0.8 (secondary end point, visual acuity outcome).
      RESULTS: In the pooled data, maximum absolute deviation of +/- 0.5 D from target
      refraction was achieved in 80% (95% confidence interval, 78%-82%) of cases.
      Visual acuity of 0.8 or more was reached in 87% (95% confidence interval, 80%
      93%) of cases. The results from the trial centers differed significantly in the
      outcomes of the primary and secondary end points (P<0.001). CONCLUSIONS: The
      study quantified benchmark levels for 2 outcome indicators in a standardized
      cataract surgery procedure. External confounding factors such as the comorbidity
      of patients, which cannot be influenced by the surgeon, were excluded. The
      derived benchmarks selectively illustrate the quality of the surgery and are
      superior to success rates published in the literature from unspecific data
      collections. This method is more suited for improving outcome quality by
      benchmarking. General methodologic problems are discussed, leading to
      recommendations for future study designs. FINANCIAL DISCLOSURE(S): The author(s)
      have no proprietary or commercial interest in any materials discussed in this
      article.

PMID- 21856013
TI  - Risk factors for hyperopia and myopia in preschool children the multi-ethnic
      pediatric eye disease and Baltimore pediatric eye disease studies.
AB  - PURPOSE: To describe the risk factors associated with hyperopia and myopia among
      children 6 to 72 months of age. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: Population-based samples of 9970 children 6 to 72 months of age
      from Los Angeles County, California, and Baltimore, Maryland. METHODS:
      Participants were preschool African-American, Hispanic, and non-Hispanic white
      children (n = 9770) from Los Angeles, California, and Baltimore, Maryland.
      Parental questionnaires and a comprehensive eye examination were administered.
      Demographic, behavioral, and clinical risk factors associated with hyperopia
      (>=2.00 diopters [D]) and myopia (<=-1.00 D) were determined. MAIN OUTCOME
      MEASURES: Odds ratios (ORs) for risk factors associated with myopia and
      hyperopia. RESULTS: Compared with non-Hispanic whites, African-American (OR, 6.0)
      and Hispanic (OR, 3.2) children were more likely to be myopic. Children 6 to 35
      months of age were more likely to be myopic compared with those 60 to 72 months
      of age (OR, >=1.7). Compared with African-American children, non-Hispanic white
      (OR, 1.63) and Hispanic (OR, 1.49) children were more likely to be hyperopic.
      Children whose parents had health insurance (OR, 1.5) and those with a history of
      maternal smoking during pregnancy (OR, 1.4) were more likely to have hyperopia.
      Astigmatism of 1.5 D or more at any axis was associated with myopia (OR, 4.37)
      and hyperopia (OR, 1.43). CONCLUSIONS: Children in specific racial or ethnic
      groups and age groups are at higher risk of having myopia and hyperopia.
      Cessation of maternal smoking during pregnancy may reduce the risk of hyperopia
      in these children. Given that both myopia and hyperopia are risk factors for the
      development of amblyopia and strabismus, these risk factors should be considered
      when developing guidelines for screening and intervention in preschool children.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 21856012
TI  - Risk factors associated with childhood strabismus: the multi-ethnic pediatric eye
      disease and Baltimore pediatric eye disease studies.
AB  - OBJECTIVE: To investigate risk factors associated with esotropia or exotropia in
      infants and young children. DESIGN: Population-based cross-sectional prevalence
      study. PARTICIPANTS: Population-based samples of 9970 children 6 to 72 months of
      age from California and Maryland. METHODS: Participants were preschool African
      American, Hispanic, and non-Hispanic white children participating in the Multi
      Ethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study. Data were
      obtained by parental interview and ocular examination. Odd ratios and 95%
      confidence intervals were calculated to evaluate the association of demographic,
      behavioral, and clinical risk factors with esotropia and exotropia. MAIN OUTCOME
      MEASURES: Odds ratios (ORs) for various risk factors associated with esotropia or
      exotropia diagnosis based on cover testing. RESULTS: In multivariate logistic
      regression analysis, esotropia was associated independently with prematurity,
      maternal smoking during pregnancy, older preschool age (48-72 months),
      anisometropia, and hyperopia. There was a severity-dependent association of
      hyperopia with the prevalence of esotropia, with ORs increasing from 6.4 for 2.00
      diopters (D) to less than 3.00 D of hyperopia, to 122.0 for 5.00 D or more of
      hyperopia. Exotropia was associated with prematurity, maternal smoking during
      pregnancy, family history of strabismus, female sex, astigmatism (OR, 2.5 for
      1.50 to <2.50 D of astigmatism, and 5.9 for >=2.5 D of astigmatism), and
      anisoastigmatism in the J0 component (OR, >=2 for J0 anisoastigmatism of >=0.25
      D). CONCLUSIONS: Prematurity and maternal smoking during pregnancy are associated
      with a higher risk of having esotropia and exotropia. Refractive error is
      associated in a severity-dependent manner to the prevalence of esotropia and
      exotropia. Because refractive error is correctable, these risk associations
      should be considered when developing guidelines for the screening and management
      of refractive error in infants and young children. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 21856014
TI  - Risk factors for decreased visual acuity in preschool children: the multi-ethnic
      pediatric eye disease and Baltimore pediatric eye disease studies.
AB  - OBJECTIVE: To investigate risk factors associated with unilateral or bilateral
      decreased visual acuity (VA) in preschool children. DESIGN: Population-based,
      cross-sectional prevalence study. PARTICIPANTS: Population-based samples of 6504
      children ages 30 to 72 months from California and Maryland. METHODS: Participants
      were preschool African-American, Hispanic, and non-Hispanic white children from
      Los Angeles, California, and Baltimore, Maryland. Data were obtained by a
      parental interview and a detailed ocular examination. Logistic regression models
      were used to evaluate the independent associations between demographic,
      behavioral, and clinical risk factors with unilateral and bilateral decreased VA.
      MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with
      interocular difference (IOD) in VA of >=2 lines with <=20/32 in the worse eye, or
      bilateral decreased VA <20/40 or <20/50 if <48 months of age. RESULTS: In
      multivariate logistic regression analysis, 2-line IOD with a VA of <=20/32 was
      independently associated with Hispanic ethnicity (OR, 2.05), esotropia (OR,
      8.98), spherical equivalent (SE) anisometropia (ORs ranging between 1.5 and 39.7
      for SE anisometropia ranging between 0.50 to <1.00 diopters [D] and >=2.00 D),
      and aniso-astigmatism in J0 or J45 (ORs ranging between 1.4 and >=5.3 for J0 or
      J45 differences ranging between 0.25 to <0.50 D and >=1.00 D). Bilateral
      decreased VA was independently associated with lack of health insurance (OR,
      2.9), lower primary caregiver education (OR, 1.7), astigmatism (OR, 2.3 and 17.6
      for astigmatism 1.00 to <2.00 D and >=2.00 D), and SE hyperopia >=4.00 D (OR,
      10.8). CONCLUSIONS: Anisometropia and esotropia are risk factors for IOD in VA.
      Astigmatism and high hyperopia are risk factors for bilateral decreased VA.
      Guidelines for the screening and management of decreased VA in preschool children
      should be considered in light of these risk associations. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 21856015
TI  - The effect of cancer therapies on pediatric anophthalmic sockets.
AB  - PURPOSE: To determine the impact of chemotherapy or external beam radiotherapy
      (EBRT) on pediatric anophthalmic sockets. DESIGN: A retrospective, nonrandomized,
      interventional cohort study. PARTICIPANTS: A total of 135 sockets of 133 children
      undergoing enucleation from late 1999 to early 2009 at the St. Jude Children's
      Research Hospital were included. METHODS: A retrospective chart review of
      outcomes after enucleation in patients treated with systemic chemotherapy or
      orbital EBRT either before or after removal of the eye compared with patients who
      received no other treatment. MAIN OUTCOME MEASURES: Incidence of implant
      exposure, migration, extrusion, socket contracture, and pyogenic granuloma
      formation. RESULTS: Retinoblastoma was the primary diagnosis in 128 eyes (95%).
      Median follow-up was 3.6 years (range, 0.1-9.3 years). Event-free course was
      observed in 94 sockets (69.6%). Complications included implant exposure (n = 28,
      20.7%), socket contracture (n = 16, 11.9%), pyogenic granuloma (n = 9, 6.7%),
      implant extrusion (n = 3, 2.2%), and migration (n = 2, 1.5%). Exposure resolved
      in 21 sockets (77.8%) and improved in 2 sockets (11.1%); 1 patient with exposure
      died. Use of prior, adjuvant, or subsequent chemotherapy increased the long-term
      risk of exposure (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.4-9.4),
      and contracture (OR could not be calculated, P<0.0001). External beam
      radiotherapy greatly increased the risk of contracture (OR 24.0; 95% CI, 6.9
      82.8) and exposure (OR 2.89; 95% CI, 1.1-7.9). CONCLUSIONS: In this unique
      pediatric population with cancer, chemotherapy and EBRT had an additive effect,
      significantly increasing the incidence of exposure and socket contracture.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 21856017
TI  - Agreement between physicians' and patients' ratings on the Montgomery-Asberg
      Depression Rating Scale.
AB  - BACKGROUND: Self-rating scales developed for monitoring depression severity are
      potentially informative and cost effective tools. There is an increasing tendency
      to use the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating
      version (MADRS-S) interchangeably. METHODS: 400 patients with major depressive
      disorder were included. Concordance between patient and physician ratings was
      measured by means of repeated MADRS and MADRS-S ratings during a six-month drug
      trial and one-year follow-up. RESULTS: Overall scores from patients and
      physicians show the same trends and both are sensitive to improvements. Our
      results, however, show only moderate to good agreement between patient and
      physician ratings. Intraclass coefficients ranged from 0.47 to 0.75 with highest
      agreement at week 8. LIMITATIONS: Generalizability is restricted to outpatients
      in general practice with moderate to severe depression. MADRS-S and MADRS scale
      definitions are similar but not identical concerning language and are scaled
      differently, 0-6 vs. 0-3, respectively, which may have influenced the results.
      The exclusion criteria restricted the range of values for the item Suicidal
      thoughts/Zest for life, which may have reduced the correlations. CONCLUSIONS:
      MADRS-S is a suitable tool for following patients' symptoms on a regular basis
      over time and may also be used to compensate for bias in physicians' ratings in
      drug trials.

PMID- 21856016
TI  - Association assessment of copy number polymorphism and risk of age-related
      macular degeneration.
AB  - PURPOSE: We previously identified a genetic copy number polymorphism (CNP147)
      that was statistically associated with age-related macular degeneration (AMD) and
      that resides downstream of the complement factor H (CFH) gene. Factor H protein
      is polymorphic at amino acid 402, in which the resulting histidine containing
      moiety has been established to impart significant risk of AMD. We present a
      method to precisely determine the exact copy number of CNP147 and examine in more
      detail the association with AMD. DESIGN: Case-control study. PARTICIPANTS: A
      total of 421 Age-Related Eye Disease Study (AREDS) subjects, of whom
      approximately 35% were diagnosed with neovascular disease, 19% were diagnosed
      with geographic atrophy, 16% were diagnosed with both, 30% were diagnosed with
      large drusen, and 215 were controls. METHODS: By using copy number assays
      available from Applied Biosystems Inc. (Carlsbad, CA), we examined 4 loci
      spanning CNP147 and neighboring CNP148 in an AREDS matched case-control sample
      set. We analyzed these data by copy number while controlling for 2 high-risk CFH
      variants, rs1061170 (Y402H) and rs1410996. We phased the high-risk CFH variants
      with CNP147 and analyzed haplotype frequencies in cases and controls. To further
      validate copy numbers, 6 Utah Centre D'etude du Polymorphism Humaine (CEPH)
      families were typed for CNP147, and the segregation was assessed. MAIN OUTCOME
      MEASURES: Increased or decreased risk of AMD from genetic loci. RESULTS: Having
      fewer than 2 copies of CNP147 was associated with an estimated 43% reduction in
      odds of having AMD in this sample set (adjusted odds ratio [OR] = 0.57, P=0.006).
      CNP148 variation is rare in Caucasians and was not statistically significant.
      Common haplotypes reveal that the risk alleles for rs1061170 and rs1410996 most
      frequently segregate with higher copy numbers for CNP147, but not exclusively,
      and that 1 haplotype that carried a deletion of CNP147 was highly protective (OR
      = 0.25 P=1.3*10(-13)) when compared with the reference. CONCLUSIONS: In this
      matched subset of AREDS subjects, after adjusting for 2 known risk variants in
      CFH, CNP147 deletion statistically associates with diminished risk for AMD.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 21856018
TI  - Partial protection against chlamydial reproductive tract infection by a
      recombinant major outer membrane protein/CpG/cholera toxin intranasal vaccine in
      the guinea pig Chlamydia caviae model.
AB  - Chlamydia trachomatis is a major cause of sexually transmitted diseases
      worldwide. There is currently no vaccine to protect against chlamydial infection
      of the female reproductive tract. Vaccine development has predominantly utilised
      the murine model; however, infection of female guinea pigs with Chlamydia caviae
      more closely resembles chlamydial infection of the human female reproductive
      tract, and presents a better model to assess potential human chlamydial vaccines.
      We immunised female guinea pigs intranasally with recombinant major outer
      membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants.
      Both systemic and mucosal immune responses were elicited in immunised animals,
      with MOMP-specific IgG and IgA present in the vaginal mucosae, and high levels of
      MOMP-specific IgG detected in the serum. Antibodies from the vaginal mucosae were
      also capable of neutralising C. caviae in vitro. Following immunisation, animals
      were challenged intravaginally with 10(2) inclusion forming units of live C.
      caviae. We observed a decrease in the duration of infection and a significant
      (p<0.025) reduction in infection load in r-MOMP-immunised animals, compared with
      animals immunised with adjuvant only. Importantly, we also observed a marked
      reduction in upper reproductive tract pathology in r-MOMP-immunised animals.
      Intranasal immunisation of female guinea pigs with r-MOMP was able to provide
      partial protection against C. caviae infection, by reducing not only chlamydial
      burden, but also upper reproductive tract pathology. This data demonstrates the
      value of using the guinea pig model to evaluate potential chlamydial vaccines for
      protection against infection and disease pathology caused by C. trachomatis in
      the female reproductive tract.

PMID- 21856019
TI  - Immunosuppressive effect of progesterone on dendritic cells in mice.
AB  - Progesterone has been demonstrated to be involved in maintaining pregnancy by
      regulating immunocytes. Dendritic cells (DCs), the most potent triggers of the
      adaptive immune response, express receptors for steroid hormones and are regarded
      as one of the primary targets of progesterone. However, the functional
      modification of DCs by progesterone remains poorly understood. Here, we report
      that progesterone does not affect the morphology or apoptosis of murine bone
      marrow-derived DCs. Progesterone-treated DCs were characterized by decreased
      expression of Ia (MHC class II), CD80 and CD86, increased production of IL-10,
      and decreased secretion of IL-12. Compared with mature DCs (mDCs), activated
      progesterone-treated DCs had a reduced capacity to stimulate CD4(+) T cell
      proliferation. The observation that progesterone-treated DCs could attenuate
      delayed-type hypersensitivity (DTH) responses in vivo suggests that progesterone
      mediates suppressive DC activity. However, transfer of progesterone-treated DCs
      into the peritoneal cavity of mice did not elevate the percentage of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Overall, our study helps
      to increase understanding of the role of DCs exposed to progesterone in the
      maintenance of pregnancy.

PMID- 21856020
TI  - Facial emotion recognition in Chinese with schizophrenia at early and chronic
      stages of illness.
AB  - Deficits in facial emotion recognition have been recognised in Chinese patients
      diagnosed with schizophrenia. This study examined the relationship between
      chronicity of illness and performance of facial emotion recognition in Chinese
      with schizophrenia. There were altogether four groups of subjects matched for age
      and gender composition. The first and second groups comprised medically stable
      outpatients with first-episode schizophrenia (n=50) and their healthy controls
      (n=26). The third and fourth groups were patients with chronic schizophrenic
      illness (n=51) and their controls (n=28). The ability to recognise the six
      prototypical facial emotions was examined using locally validated coloured
      photographs from the Japanese and Caucasian Facial Expressions of Emotion.
      Chinese patients with schizophrenia, in both the first-episode and chronic
      stages, performed significantly worse than their control counterparts on overall
      facial emotion recognition, (P<0.001), with specific impairment in identifying
      surprise, fear and disgust. The level of deficit was similar at the two stages of
      illness. Findings suggest that impaired recognition of facial emotion did not
      appear to have worsened over the course of disease progression, suggesting that
      recognition of facial emotion is a rather stable trait of the illness. The
      emotion-specific deficit may have implications for understanding the social
      difficulties in schizophrenia.

PMID- 21856021
TI  - Response of proinflammatory and anti-inflammatory cytokines in calves with
      subclinical bovine viral diarrhea challenged with bovine herpesvirus-1.
AB  - The aim of this work was to investigate the susceptibility of calves infected
      with bovine viral diarrhea virus (BVDV) against secondary infections. For this
      purpose, the profile of cytokines implicated in the immune response of calves
      experimentally infected with a non-cytopathic strain of BVDV type-1 and
      challenged with bovine herpesvirus 1.1 (BHV-1.1) was evaluated in comparison with
      healthy animals challenged only with BHV-1.1. The immune response was measured by
      serum concentrations of cytokines (IL-1beta, TNFalpha, IFNgamma, IL-12, IL-4 and
      IL-10), acute phase proteins (haptoglobin, serum amyloid A and fibrinogen) and
      BVDV and BHV-1.1 specific antibodies. BVDV-infected calves displayed a great
      secretion of TNFalpha and reduced production of IL-10 following BHV-1 infection,
      leading to an exacerbation of the inflammatory response and to the development of
      more intense clinical symptoms and lesions than those observed in healthy animals
      BHV-1-inoculated. A Th1 immune response, based on IFNgamma production and on the
      absence of significant changes in IL-4 production, was observed in both groups of
      BHV-1-infected calves. However, whereas the animals inoculated only with BHV-1
      presented an IFNgamma response from the start of the study and high expression of
      IL-12, the BVDV-infected calves showed a delay in the IFNgamma production and low
      levels of IL-12. This alteration in the kinetic and magnitude of these cytokines,
      involved in cytotoxic mechanisms responsible for limiting the spread of secondary
      pathogens, facilitated the dissemination of BHV-1.1 in BVDV-infected calves.

PMID- 21856022
TI  - Improved insulin sensitivity by the angiotensin receptor antagonist irbesartan in
      patients with systolic heart failure: a randomized double-blinded placebo
      controlled study.
AB  - BACKGROUND: Impaired insulin sensitivity is common in patients with chronic
      systolic heart failure (CHF) and contributes to symptomatic status and impaired
      prognosis. A specific metabolic effect to improve insulin sensitivity in diabetic
      patients has been reported for some but not all angiotensin II-receptor
      antagonists. We aimed to test the ancillary metabolic effect of irbesartan on
      insulin sensitivity in patients with CHF. METHODS AND PARTICIPANTS: In this
      placebo-controlled double-blinded study 36 non-diabetic patients with stable
      ischemic CHF (age 63 +/- 9 years, peak VO(2) 16.6 +/- 4.8 ml/kg/min, LVEF 32 +/-
      9%) were randomized to irbesartan 300 mg/d vs placebo on top of standard CHF
      therapy. Body composition (dual energy X-ray absorptiometry), clinical status,
      peripheral vasodilator capacity (plethysmography) and neuroendocrine and
      metabolic profiles were assessed. Primary endpoint was the change of whole body
      insulin sensitivity after 4 months of treatment assessed by intravenous glucose
      tolerance testing and minimal modeling. RESULTS: Insulin sensitivity improved by
      26% (p<0.001) in the irbesartan group, but not in the placebo group (treatment
      effect: 1.044 min(-1).MUU.ml(-1).10(4); 95%CI 0.45 to 1.64, p=0.0026). Treatment
      effects on systolic and diastolic blood pressure were -11 (95%CI -21 to -1)mmHg
      and -8 (95%CI -15 to -3)mmHg, respectively. Peripheral vasodilator capacity
      improved by 14% (p=0.016). Change in insulin sensitivity correlated with
      increased vasodilator capacity (R=0.47, p=0.021). Body composition and clinical
      status were not different after 4 months of therapy. Also adiponectin, resistin,
      cytokine profile, and asymmetric dimethylarginine (ADMA) were not changed after
      this short-term intervention. CONCLUSION: Therapy with irbesartan improved
      insulin sensitivity in patients with chronic heart failure. Improved peripheral
      vasodilator capacity may contribute to the metabolic effect. (Clinical trials
      identifier: NCT00347087).

PMID- 21856023
TI  - Physical activity in relation to exercise capacity in chronic heart failure
      patients.

PMID- 21856024
TI  - Angina pectoris caused by the extrinsic compression of coronary artery by primary
      thymic mucinous adenocarcinoma.

PMID- 21856025
TI  - Clinical significance of active myeloperoxidase in carotid atherosclerotic
      plaques.

PMID- 21856026
TI  - Intravascular ultrasound findings in left main radiation-associated coronary
      artery disease.

PMID- 21856027
TI  - Serum ferritin and acute coronary syndrome: a strong prognostic factor?

PMID- 21856028
TI  - The effect of neighbourhood definitions on spatio-temporal models of disease
      outbreaks: Separation distance versus range overlap.
AB  - The definition of the spatial relatedness between infectious and susceptible
      animal groups is a fundamental component of spatio-temporal modelling of disease
      outbreaks. A common neighbourhood definition for disease spread in wild and feral
      animal populations is the distance between the centroids of neighbouring group
      home ranges. This distance can be used to define neighbourhood interactions, and
      also to describe the probability of successful disease transmission. Key
      limitations of this approach are (1) that a susceptible neighbour of an
      infectious group with an overlapping home range - but whose centroid lies outside
      the home range of an infectious group - will not be considered for disease
      transmission, and (2) the degree of overlap between the home ranges is not taken
      into account for those groups with centroids inside the infectious home range. We
      assessed the impact of both distance-based and range overlap methods of disease
      transmission on model-predicted disease spread. Range overlap was calculated
      using home ranges modelled as circles. We used the Sirca geographic automata
      model, with the population data from a nine-county study area in Texas that we
      have previously described. For each method we applied 100 model repetitions, each
      of 100 time steps, to 30 index locations. The results show that the rate of
      disease spread for the range-overlap method is clearly less than the distance
      based method, with median outbreaks modelled using the latter being 1.4-1.45
      times larger. However, the two methods show similar overall trends in the area
      infected, and the range-overlap median (48 and 120 for cattle and pigs,
      respectively) falls within the 5th-95th percentile range of the distance-based
      method (0-96 and 0-252 for cattle and pigs, respectively). These differences can
      be attributed to the calculation of the interaction probabilities in the two
      methods, with overlap weights generally resulting in lower interaction
      probabilities. The definition of spatial neighbourhood has important implications
      for models used in decision-support systems for disease preparedness and
      response. This research presents a first step towards more realistic
      representations that could be used in spatio-temporal models of disease
      outbreaks.

PMID- 21856029
TI  - GEOVET 2010A Conference on the Application of Spatial Analytical Methods Used in
      Animal Health, GEOVET - 2010 Sydney, Australia. Preface.

PMID- 21856030
TI  - The antimicrobial activities of the cinnamaldehyde adducts with amino acids.
AB  - Cinnamaldehyde is a well-established natural antimicrobial compound. It is
      probable for cinnamaldehyde to react with amino acid forming Schiff base adduct
      in real food system. In this paper, 9 such kind of adducts were prepared by the
      direct reaction of amino acids with cinnamaldehyde at room temperature. Their
      antimicrobial activities against Bacillus subtilis, Escherichia coli and
      Saccharomyces cerevisiae were evaluated with benzoic acid as a reference. The
      adducts showed a dose-dependent activities against the three microbial strains.
      Both cinnamaldehyde and their adducts were more active against B. subtilis than
      on E. coli, and their antimicrobial activities were higher at lower pH. Both
      cinnamaldehyde and its adducts were more active than benzoic acid at the same
      conditions. The adduct compound A was non-toxic by primary oral acute toxicity
      study in mice. However, in situ effect of the adduct compound A against E. coli
      was a little lower than cinnamaldehyde in fish meat. This paper for the first
      time showed that the cinnamaldehyde adducts with amino acids had similar strong
      antimicrobial activities as cinnamaldehyde, which may provide alternatives to
      cinnamaldehyde in food to avoid the strong unacceptable odor of cinnamaldehyde.

PMID- 21856031
TI  - Inverse association between fruit, legume, and cereal fiber and the risk of
      metabolic syndrome: Tehran Lipid and Glucose Study.
AB  - AIMS: To evaluate the association between total dietary fiber and its types and
      sources with the risk of MetS. METHODS: This population-based cross-sectional
      study was conducted on a representative sample of 2457 adults (1327 male and 1130
      female), aged 19-84 years. Dietary intake was assessed using a validated
      semiquantitative food-frequency questionnaire. Anthropometrics, blood pressure,
      and fasting blood glucose and lipids were measured according to standard
      protocols. The MetS was defined according to definition by Adult Treatment Panel
      III. RESULTS: Multivariate-adjusted odds ratio of MetS between highest and lowest
      quartiles was 0.53 (95% CI: 0.39-0.74; P for trend <0.05) for total dietary
      fiber, 0.60 (0.43-0.84; P for trend <0.05) for soluble fiber, and 0.51 (0.35
      0.72; P for trend <0.05) for insoluble fiber. Among sources of dietary fiber,
      fruit fiber (OR: 0.51; 95% CI: 0.37-0.72), cereal fiber (0.74; 0.57-0.97), and
      legume fiber (0.73; 0.53-0.99) were inversely associated with the risk of MetS,
      after adjustment for confounding factors. Intake of vegetable fiber and nut fiber
      were unrelated to the risk of MetS. CONCLUSIONS: Total dietary fiber, soluble-
      and insoluble fiber, fruit fiber, cereal fiber and legume fiber were associated
      with a protective effect for the presence of MetS among this Tehranian
      population.

PMID- 21856032
TI  - High-density lipoprotein phospholipids interfere with dendritic cell Th1
      functional maturation.
AB  - Lipoproteins are both lipid carriers in the blood and regulators of essential
      biological processes. Several studies demonstrated that lipoproteins modified
      during pathological conditions could alter dendritic cell (DC) maturation. Here
      the immune function of non-pathological lipoproteins is addressed by analysing
      their impact on human DC maturation triggered by TLR ligands. Upon TLR4
      stimulation, low- and high-density lipoproteins (LDL and HDL) strongly inhibited
      the ability of DC to induce a Th1 response of T cells, characterized by high
      levels of IFNgamma secretion, whereas the effect of very low-density lipoprotein
      was subject to variations. HDL also inhibited the Th1 function of DC stimulated
      by TLR1/2 and TLR2/6 ligands. The phospholipid fraction from HDL retained the
      inhibitory activity of the lipoprotein. We identified the 1-palmitoyl-2-linoleyl
      phosphatidylcholine (PLPC) as one active phospholipid that inhibited the Th1
      function of mature DCs whereas the dipalmitoyl-phosphatidylcholine had no
      significant effect. The treatment of DC by PLPC, 24h before TLR4 stimulation,
      resulted in reduced activation of NF-kappaB. This study shows that some HDL
      phospholipids have a direct immunoregulatory function, by modulating DC ability
      to activate a Th1 response of T cells.

PMID- 21856033
TI  - The new face of anaphylatoxins in immune regulation.
AB  - Anaphylatoxins are a group of small peptides (i.e. C3a, C4a and C5a) generated by
      complement activation and play important roles in innate immunity through the
      initiation and regulation of inflammatory responses. More recent studies have
      revealed that, in addition to their traditional roles in inflammation,
      anaphylatoxins also significantly influence the adaptive immune response. It does
      so through a number of mechanisms and by targeting various cells. One important
      mechanism is that anaphylatoxins (C3a, C5a) act on their receptors expressed on
      innate immune cells such as dendritic cells. This modulates cell activation and
      their functions in initiating and regulating T cell responses and thus
      influencing T cell immunity. This review provides an overview of anaphylatoxins
      in adaptive immune regulation focusing on their roles in modulating dendritic
      cell and macrophage functions and the importance of local production of
      complement in this regulation.

PMID- 21856034
TI  - Complement activation as a biomarker for Alzheimer's disease.
AB  - There is increasing evidence from genetic, immunohistochemical, proteomic and
      epidemiological studies as well as in model systems that complement activation
      has an important role in the pathogenesis of Alzheimer's disease (AD). The
      complement cascade is an essential element of the innate immune response. In the
      brain complement proteins are integral components of amyloid plaques and
      complement activation occurs at the earliest stage of the disease. The complement
      cascade has been implicated as a protective mechanism in the clearance of
      amyloid, and in a causal role through chronic activation of the inflammatory
      response. In this review we discuss the potential for complement activation to
      act as a biomarker for AD at several stages in the disease process. An accurate
      biomarker that has sufficient predictive, diagnostic and prognostic value would
      provide a significant opportunity to develop and test for effective novel
      therapies in the treatment of AD.

PMID- 21856035
TI  - RNAi knockdown of parafusin inhibits the secretory pathway.
AB  - Several glycolytic enzymes and their isoforms have been found to be important in
      cell signaling unrelated to glycolysis. The involvement of parafusin (PFUS), a
      member of the phosphoglucomutase (PGM) superfamily with no phosphoglucomutase
      activity, in Ca(2+)-dependent exocytosis has been controversial. This protein was
      first described in Paramecium tetraurelia, but is widely found. Earlier work
      showed that parafusin is a secretory vesicle scaffold component with unusual post
      translational modifications (cyclic phosphorylation and phosphoglucosylation)
      coupled to stages in the exocytic process. Using RNAi, we demonstrate that
      parafusin synthesis can be reversibly blocked, with minor or no effect on other
      PGM isoforms. PFUS knockdown produces an inhibition of dense core secretory
      vesicle (DCSV) synthesis leading to an exo(-) phenotype. Although cell growth is
      unaffected, vesicle content is not packaged properly and no new DCSVs are formed.
      We conclude that PFUS and its orthologs are necessary for proper scaffold
      maturation. Because of this association, parafusin is an important signaling
      component for regulatory control of the secretory pathway.

PMID- 21856036
TI  - Molecular mechanism and structural basis of interactions of dipeptidyl peptidase
      IV with adenosine deaminase and human immunodeficiency virus type-1 transcription
      transactivator.
AB  - Dipeptidyl peptidase IV (DPPIV or CD26) is a multifunctional membrane
      glycoprotein. As an exopeptidase it regulates the activity of a series of
      biologically important peptides. Through its interaction with specific proteins
      and peptides, DPPIV is also involved in a wide range of biologically relevant
      processes such as cell adhesion, T cell activation and apoptosis. In this paper,
      we review our recent studies on the interactions of DPPIV with adenosine
      deaminase (ADA) and the transcription transactivator of the human
      immunodeficiency virus type-1 (HIV-1 Tat) as revealed by three-dimensional
      structure reconstructed by single particle analysis of cryo-electron microscopy
      (EM) and crystal structures of the human DPPIV-bovine ADA complex as well as the
      crystal structures of DPPIV in complex with HIV-1 Tat-derived nonapeptides. These
      results contribute importantly to the clarification of the molecular mechanisms
      of this multifunctional protein. The biological relevance of these interactions
      is discussed.

PMID- 21856037
TI  - Gibberellins negatively regulate light-induced nitrate reductase activity in
      Arabidopsis seedlings.
AB  - In the present study, the role of phytohormone gibberellins (GAs) on regulating
      the nitrate reductase (NR) activity was tested in Arabidopsis seedlings. The NR
      activity in light-grown Col-0 seedlings was reduced by exogenous GA3 (an active
      form of GAs), but enhanced by exogenous paclobutrazol (PAC, a gibberellin
      biosynthesis inhibitor), suggesting that GAs negatively regulate the NR activity
      in light-grown seedlings. Light is known to influence the NR activity through
      both photosynthesis and phytochromes. When etiolated seedlings were transferred
      to white or red light, both exogenously applied GA3 and PAC were found to
      function on the NR activity only in the presence of sucrose, implying that GAs
      are not involved in light signaling-induced but negatively regulate photoproducts
      induced NR activity. NR is regulated by light mainly at two levels: transcript
      level and post-translational level. Our reverse transcription (RT)-PCR assays
      showed that GAs did not affect the transcript levels of NIA1 and NIA2, two genes
      that encode NR proteins. But the divalent cations (especially Mg2+) were required
      for GAs negative regulation of NR activity, in view of the importance of divalent
      cations during the process of post-translational regulation of NR activity, which
      indicates that GAs very likely regulate the NR activity at the post-translational
      level. In the following dark-light shift analyses, GAs were found to accelerate
      dark-induced decrease, but retard light-induced increase of the NR activity.
      Furthermore, it was observed that application of G3 or PAC could impair diurnal
      variation of the NR activity. These results collectively indicate that GAs play a
      negative role during light regulation of NR activity in nature.

PMID- 21856038
TI  - Novel vitamin E forms in leaves of Kalanchoe daigremontiana and Phaseolus
      coccineus.
AB  - In the present study, we isolated novel tocochromanols from green leaves of
      Kalanchoe daigremontiana and primary leaves of etiolated seedlings of Phaseolus
      coccineus that were identified as beta-, gamma-, and delta-tocomonoenols with
      unsaturation at the terminal isoprene unit of the side chain. The content of
      gamma-tocomonoenol in leaves of etiolated bean increased gradually with the age
      of seedlings, reaching 50% of the gamma-tocopherol level in 40-day-old plants.
      The content of this compound in leaves was increased by short illumination of
      etiolated plants and by addition of homogentisic acid, a biosynthetic precursor
      of tocopherols. These data indicated that gamma-tocomonoenol is synthesized de
      novo from homogentisic acid and tetrahydro-geranylgeraniol diphosphate, a phytol
      precursor. Based on these results, a biosynthetic pathway of tocomonoenols is
      proposed.

PMID- 21856039
TI  - Treatment of erosive oral lichen planus with local ultraviolet B phototherapy.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease that can
      significantly affect the patient's quality of life. OBJECTIVE: We sought to
      demonstrate the therapeutic efficacy of local ultraviolet (UV) B phototherapy in
      OLP. METHODS: Patients with biopsy-confirmed erosive OLP recalcitrant to previous
      medical therapy were treated with the TheraLight UV 120-2 system (TheraLight Inc,
      Carlsbad, CA). Lesions were accessed directly using a flexible fiber guide. Local
      phototherapy was delivered 3 times a week, with gradual increase in UVB dose
      every other session. Affected oral mucosa was defined as the area showing
      erosions or symptomatic reticular lesions. Complete response was defined as
      reduction of at least 80% in the affected mucosal area, and partial response was
      defined as a reduction of 50% to 80% in the affected mucosal area. The primary
      end point was efficacy after 8 weeks of treatment. RESULTS: Fourteen patients
      were included in the study. Nine achieved complete response and 5 partial
      response after 8 weeks. Ten patients were continued on maintenance therapy and
      were able to maintain their response for another 29 weeks. None of the patients
      showed any serious side effects from local UVB therapy. LIMITATIONS: The study
      was performed in a small series of patients at a single medical center. Further
      studies with larger patient samples are required to validate our findings.
      CONCLUSION: Local UVB phototherapy may be a promising treatment modality for
      erosive OLP.

PMID- 21856041
TI  - Ichthyosis prematurity syndrome: clinical evaluation of 17 families with a rare
      disorder of lipid metabolism.
AB  - BACKGROUND: Ichthyosis prematurity syndrome (IPS) is classified as a syndromic
      congenital ichthyosis based on the presence of skin changes at birth,
      ultrastructural abnormalities in the epidermis, and extracutaneous
      manifestations. Recently, mutations in the fatty acid transporter protein 4 gene
      have been identified in patients with IPS. OBJECTIVE: We sought to perform a
      detailed clinical evaluation of patients with IPS identified in Norway. METHODS:
      Clinical examination and follow-up of all patients (n = 23) and light and
      electron microscopic examination of skin biopsy specimens were performed.
      RESULTS: IPS was characterized prenatally by ultrasound findings of
      polyhydramnios, separation of membranes, echogenic amniotic fluid, and clear
      chorionic fluid. All patients were born prematurely with sometimes life
      threatening neonatal asphyxia; this was likely caused by aspiration of corneocyte
      containing amniotic fluid as postmortem examination of lung tissue in two
      patients revealed keratin debris filling the bronchial tree and alveoli. The skin
      appeared erythrodermic, swollen, and covered by a greasy, thick vernix caseosa
      like "scale" at birth, and evolved rapidly to a mild chronic ichthyosis. Many
      patients subsequently had chronic, severe pruritus. Histopathologic and
      ultrastructural examination of skin biopsy specimens showed hyperkeratosis,
      acanthosis, dermal inflammation, and characteristic aggregates of curved lamellar
      structures in the upper epidermis. Peripheral blood eosinophilia was invariably
      present and most patients had increased serum immunoglobulin E levels. Over 70%
      of the patients had a history of respiratory allergy and/or food allergy.
      LIMITATIONS: The study included only 23 patients because of the rarity of the
      disease. CONCLUSION: IPS is characterized by defined genetic mutations, typical
      ultrastructural skin abnormalities, and distinct prenatal and postnatal clinical
      features.

PMID- 21856042
TI  - A 12-year review of Staphylococcus aureus bloodstream infections in haemodialysis
      patients: more work to be done.
AB  - Staphylococcus aureus bloodstream infections (BSI) are a significant cause of
      morbidity and mortality in haemodialysis patients. This study describes a 12-year
      retrospective review of S. aureus BSI in a large haemodialysis centre in a
      tertiary referral hospital. The overall rate of S. aureus BSI was 17.9 per 100
      patient-years (range 9.7-36.8). The rate of meticillin-resistant S. aureus (MRSA)
      BSI was 5.6 per 100 patient-years (range 0.9-13.8). Infective complications
      occurred in 11% of episodes, the most common being infective endocarditis (7.6%).
      Ten percent of patients died within 30 days of S. aureus being isolated from
      blood. Most cases of S. aureus BSI (83%) were related to vascular catheters. The
      provision of lower-risk vascular access, such as arteriovenous fistulae, and
      reduced use of intravascular catheters should be priorities in all haemodialysis
      units. Where alternative vascular access cannot be established, interventions to
      reduce the risk of catheter-related infections should be implemented to reduce
      morbidity and mortality in this vulnerable patient group.

PMID- 21856040
TI  - Dermatologist preferences for first-line therapy of moderate to severe psoriasis
      in healthy adult patients.
AB  - BACKGROUND: Despite increasing therapies for moderate to severe psoriasis,
      dermatologists' treatment preferences are unknown. OBJECTIVE: We sought to assess
      dermatologists' preferences for first-line treatments and their selection
      determinants. METHODS: We surveyed 1000 US dermatologists (500 National Psoriasis
      Foundation and 500 American Academy of Dermatology members who treat psoriasis)
      about their preferences for first-line treatment of moderate to severe psoriasis
      in healthy adults of childbearing age using standardized patient vignettes.
      RESULTS: The response rate was 39% (N = 387). Preferred therapies for male and
      female patients were: ultraviolet (UV) B (40% and 56%, respectively), etanercept
      (15% and 19%), methotrexate (16% and 4%), and adalimumab (12% and 10%). Of
      respondents, 66% administered phototherapy in their practice. After adjusting for
      all physician characteristics, those preferring first-line UVB for male or female
      patients were significantly more likely to have phototherapy in their practice
      (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.8-6.6 and OR 2.8, 95% CI 1.5
      5.3, respectively) and to have used UVB in more than 10 patients in the last 3
      months (OR 8.0, 95% CI 3.9-16.4; OR 9.6, 95% CI 4.3-21.6). Dermatologists in the
      Midwest were more likely than those in the Northeast to prefer adalimumab first
      line for male and female patients. LIMITATIONS: We surveyed only dermatologists
      with interest in treating psoriasis and elicited their treatment preferences for
      a single base case scenario. Treatment preferences may differ between survey
      respondents and nonrespondents. CONCLUSION: UVB is most commonly preferred as a
      first-line treatment for moderate to severe psoriasis in healthy adults, and
      preferences vary based on region, phototherapy availability, and prior treatment
      use.

PMID- 21856043
TI  - Sulfur mustard exposure presenting to a community emergency department.
AB  - We report dermal exposure to a chemical warfare agent, sulfur mustard, in a 28
      year-old commercial fisherman. Chemical warfare agents such as sulfur mustard are
      considered potential terrorist weapons, and suspected exposure requires
      notification of federal authorities. We address potential pitfalls when alerting
      authorities and methods to avoid such obstacles, and we describe the clinical
      management of sulfur mustard toxicity.

PMID- 21856044
TI  - Intraosseous versus intravenous vascular access during out-of-hospital cardiac
      arrest: a randomized controlled trial.
AB  - STUDY OBJECTIVE: Intraosseous needle insertion during out-of-hospital cardiac
      arrest is rapidly replacing peripheral intravenous routes in the out-of-hospital
      setting. However, there are few data directly comparing the effectiveness of
      intraosseous needle insertions with peripheral intravenous insertions during out
      of-hospital cardiac arrest. The objective of this study is to determine whether
      there is a difference in the frequency of first-attempt success between humeral
      intraosseous, tibial intraosseous, and peripheral intravenous insertions during
      out-of-hospital cardiac arrest. METHODS: This was a randomized trial of adult
      patients experiencing a nontraumatic out-of-hospital cardiac arrest in which
      resuscitation efforts were initiated. Patients were randomized to one of 3 routes
      of vascular access: tibial intraosseous, humeral intraosseous, or peripheral
      intravenous. Paramedics received intensive training and exposure to all 3 methods
      before study initiation. The primary outcome was first-attempt success, defined
      as secure needle position in the marrow cavity or a peripheral vein, with normal
      fluid flow. Needle dislodgement during resuscitation was coded as a failure to
      maintain vascular access. RESULTS: There were 182 patients enrolled, with 64
      (35%) assigned to tibial intraosseous, 51 (28%) humeral intraosseous, and 67
      (37%) peripheral intravenous access. Demographic characteristics were similar
      among patients in the 3 study arms. There were 130 (71%) patients who experienced
      initial vascular access success, with 17 (9%) needles becoming dislodged, for an
      overall frequency of first-attempt success of 113 (62%). Individuals randomized
      to tibial intraosseous access were more likely to experience a successful first
      attempt at vascular access (91%; 95% confidence interval [CI] 83% to 98%)
      compared with either humeral intraosseous access (51%; 95% CI 37% to 65%) or
      peripheral intravenous access (43%; 95% CI 31% to 55%) groups. Time to initial
      success was significantly shorter for individuals assigned to the tibial
      intraosseous access group (4.6 minutes; interquartile range 3.6 to 6.2 minutes)
      compared with those assigned to the humeral intraosseous access group (7.0
      minutes; interquartile range 3.9 to 10.0 minutes), and neither time was
      significantly different from that of the peripheral intravenous access group (5.8
      minutes; interquartile range 4.1 to 8.0 minutes). CONCLUSION: Tibial intraosseous
      access was found to have the highest first-attempt success for vascular access
      and the most rapid time to vascular access during out-of-hospital cardiac arrest
      compared with peripheral intravenous and humeral intraosseous access.

PMID- 21856045
TI  - Hospital environment and invasive aspergillosis in patients with hematologic
      malignancy.
AB  - BACKGROUND: To determine whether there is a correlation between sources of
      Aspergillus spores in a high-efficiency particulate air (HEPA)-filtered
      environment and nosocomial invasive aspergillosis (IA), we performed a detailed
      environmental assessment and case review. METHODS: From April to October 2004,
      626 bioaerosol samples, 1,257 surface samples, and 607 water samples were
      obtained from 74 HEPA-filtered air hospital rooms occupied by 458 patients with
      hematologic malignancies. Samples were collected prospectively from the room
      before and after cleaning within 1 hour of patient admission or discharge.
      Aspergillus spp was isolated from 21 surface samples and 46 bioaerosol samples.
      Interestingly, Aspergillus spp was not isolated from any water samples. RESULTS:
      Aspergillus spp was isolated from 21 surface samples and 46 bioaerosol samples.
      Interestingly, Aspergillus spp were not isolated from any water samples. The
      majority (90%) of the positive bioaerosol samples had <= 10 colony-forming units
      of Aspergillus/m3 of air. Only 2 patients developed nosocomial IA. No
      correlations were found between Aspergillus species isolated from the hospital
      rooms and those causing IA. CONCLUSION: The risk of hematologic malignancy
      patients acquiring nosocomial aspergillosis from water or HEPA-filtered air is
      very low.

PMID- 21856046
TI  - Outbreak of bloodstream infections because of Serratia marcescens in a pediatric
      department.
AB  - BACKGROUND: Serratia marcescens can cause health care-associated infections. We
      herewith report the investigation and control of an outbreak of S marcescens
      bloodstream infections (BSI) in a general pediatric department. METHODS: From
      April to May 2009, temporally related cases of S marcescens BSI occurred in a 40
      bed general pediatric department of a tertiary care hospital. An outbreak
      investigation including case identification, review of medical records,
      environmental cultures, patients' surveillance cultures, personnel hand cultures,
      pulsed-field gel electrophoresis, and a case-control study were conducted.
      Controls were patients without S marcescens BSI but hospitalized in the
      department for at least 48 hours during the outbreak. Enhanced infection control
      measures were immediately implemented by the Infection Control Committee.
      RESULTS: During the study period, 4 patients developed BSI because of a S
      marcescens strain demonstrating the same antimicrobial susceptibility pattern as
      well as the same molecular profile. Patients' surveillance cultures and personnel
      hand cultures were negative. In 1 case-patient, S marcescens grew from cultures
      of intravenous infusion systems. In the case-control study performed, there were
      no differences in demographics, intravenously administered medications, or place
      of hospital stay. Case patients had changes in vascular access significantly more
      frequently than controls. No S marcescens infections occurred in the department
      during the 18 months following implementation of the enhanced infection control
      measures. CONCLUSION: Prompt recognition and strict adherence to infection
      control measures are of paramount importance in combating an outbreak of S
      marcescens bloodstream infection.

PMID- 21856047
TI  - Brain tissue volumes by APOE genotype and leisure activity-the AGES-Reykjavik
      Study.
AB  - This study investigates the association of the APOE epsilon4 allele and leisure
      activity with brain tissue volumes, including white matter hyperintensities
      (WMH), in a population-based cohort of 4303 nondemented individuals, aged 66-96
      years. APOE epsilon4 carriers were shown to have greater WMH and cerebrospinal
      fluid (CSF) volumes than noncarriers but smaller gray matter (GM) volumes. There
      was no significant difference in white matter (WM) and total brain parenchymal
      (TBP) volumes between APOE epsilon4 carriers and noncarriers. Tests for linear
      trend showed that individuals with lower leisure activity levels had greater WMH
      and CSF volumes, smaller TBP, WM and GM volumes than those with the highest
      levels of participation. The significant positive trend of the leisure activity
      with the brain tissue volumes was observed in the APOE epsilon4 carriers as well
      as in noncarriers after adjustment for demographic and health factors. These
      cross-sectional data suggest leisure activity is associated with tissue volumes
      in the brain irrespective of the APOE epsilon4 risk allele status.

PMID- 21856048
TI  - Synthesis and biological activity of novel tiliroside derivants.
AB  - A series of new tiliroside derivatives were synthesized and characterized by
      analytical (1)H NMR, (13)C NMR and mass spectrometry. All of the compounds were
      evaluated for anti-diabetic properties in vitro using HepG2 cells. Compounds 3c,
      3d, and 3i-l caused significant enhancements in glucose consumption by insulin
      resistant HepG2 cells compared with control cells and cells that were exposed to
      metformin (an anti-diabetic drug). Moreover, compound 3l significantly activated
      adenosine 5'-monophosphate-activated protein kinase activity and reduced acetyl
      CoA carboxylase activity. Thus, the tiliroside derivative 3l offers potential to
      be developed as a new approach for treating type II diabetes.

PMID- 21856049
TI  - Overcoming human P-glycoprotein-dependent multidrug resistance with novel dihydro
      beta-agarofuran sesquiterpenes.
AB  - Sixteen (1-16) dihydro-beta-agarofuran sesquiterpenes were isolated from the
      fruits of Maytenus jelskii and evaluated against mammalian cells with a multidrug
      resistance phenotype mediated by the overexpression of the human P-glycoprotein.
      Their stereostructures have been elucidated on the basis of spectroscopic
      analysis, including 1D and 2D NMR techniques, CD studies, chemical correlations
      and biogenetic means. Eight compounds from this series were discovered as potent
      chemosensitizers (1, 2, 4, 6, 8, 9, 11 and 14), showing similar effectiveness to
      or higher than the classical P-glycoprotein reversal agent verapamil, a first
      generation chemosensitizer, when reversing resistance to daunomycin and
      vinblastine. Detailed structure-activity relationships revealed that aromatic
      substituents at the 6 and 9-position of the sesquiterpene scaffold were able to
      modulate the intensity of inhibition.

PMID- 21856050
TI  - Tyrosyl-tRNA synthetase inhibitors as antibacterial agents: synthesis, molecular
      docking and structure-activity relationship analysis of 3-aryl-4-arylaminofuran
      2(5H)-ones.
AB  - Thirty-five 3-aryl-4-arylaminofuran-2(5H)-one derivatives were designed, prepared
      and tested for their inhibitory activity against tyrosyl-tRNA synthetase. Out of
      these compounds, 3-(3-bromophenyl)-4-(3,5-dichlorophenylamino)furan-2(5H)-one
      (35) was the most active with IC(50) of 0.09 +/- 0.02 MUM. The structure-activity
      relationship revealed that introduction of chlorine atoms at both meta positions
      of aniline moiety significantly increased the enzyme inhibitory activity. The
      results of antibacterial assay revealed that the tested compounds showed good
      activity against Gram-positive bacteria, with 35 being the most potent with
      MIC(50) of 0.06 MUg/mL against Staphylococcus aureus ATCC 25923. Molecular
      docking of 35 into S. aureus tyrosyl-tRNA synthetase active site was also
      performed. The inhibitor snugly fitting the active site may well explain its
      excellent inhibitory activity.

PMID- 21856051
TI  - Does an Immediate Life Support (ILS) course enhance clinical practice? The
      students' perceptions.
AB  - This descriptive study evaluates whether the Immediate Life Support (ILS) course
      enhanced final year adult branch nursing students' ability to assess and
      initially manage the care of deteriorating patients. A thirty point likert scale
      questionnaire was used to collect quantitative data from final year adult branch
      nursing students in one Higher Education Institution in the United Kingdom. A
      comment box permitted the compilation of qualitative remarks. An 84% (n=149)
      response rate was achieved. The responses demonstrated a positive endorsement of
      the ILS course as part of the final year adult branch programme. Data also
      suggested that knowledge and skills learned during the ILS course were extremely
      useful for students and enhanced their clinical practice. Findings indicate that
      providing students with the opportunity to participate in the ILS course enhanced
      their ability to practice in a more confident manner. Furthermore, findings
      suggest that undertaking the ILS course provides the student with the skills to
      recognise the deteriorating patient and may have the potential of improving
      patient care. New knowledge from this research suggests that the ILS course does
      prepare students for practice and may go some way to assist students make the
      transition from student to registered nurse.

PMID- 21856052
TI  - Lead-210 and Beryllium-7 fallout rates on the southeastern coast of Brazil.
AB  - Total 210Pb and 7Be fallout rates were measured on the coastal region of Niteroi,
      Brazil. The monthly depositional flux of 210Pb and 7Be varied by a factor of 26,
      from 1.7 to 43.3 mBq cm-2 year-1 and ~27, from 7.5 to 203.5 mBq cm-2 year-1,
      respectively. The relatively large oscillations in the depositional flux of 210Pb
      at this study site were likely due to variations in air mass sources, while the
      7Be fluctuations may be driven by a combination of weather conditions. Local
      geology could support the periodic high fluxes of 210Pb from continental air
      masses, as shifting oceanic wind sources were affirmed by the uncorrelated 210Pb
      and 7Be fallout activities and 7Be/210Pb ratios. The 210Pb atmospheric deposition
      was found to be in agreement with local sediment inventories, an important
      consideration in geochemical studies that estimate sedimentation processes.

PMID- 21856053
TI  - Short and long term dispersion patterns of radionuclides in the atmosphere around
      the Fukushima Nuclear Power Plant.
AB  - The Chernobyl accident and unfortunately the recent accident at the Fukushima 1
      Nuclear Power Plant are the most serious accidents in the history of the nuclear
      technology and industry. Both of them have a huge and prolonged impact on
      environment as well as human health. Therefore, any technological developments
      and strategies that could diminish the consequences of such unfortunate events
      are undisputedly the most important issues of research. Numerical simulations of
      dispersion of radionuclides in the atmosphere after an accidental release can
      provide with a reliable prediction of the path of the plume. In this study we
      present a short (one month) and a long (11 years) term statistical study for the
      Fukushima 1 Nuclear Power Plant to estimate the most probable dispersion
      directions and plume structures of radionuclides on local scale using a Gaussian
      dispersion model. We analyzed the differences in plume directions and structures
      in case of typical weather/circulation pattern and provided a statistical
      climatological method for a "first-guess" approximation of the dispersion of
      toxic substances. The results and the described method can support and used by
      decision makers in such important cases like the Fukushima accident.

PMID- 21856054
TI  - Metabolic responses of Eisenia fetida after sub-lethal exposure to organic
      contaminants with different toxic modes of action.
AB  - Nuclear magnetic resonance (NMR)--based metabolomics has the potential to
      identify toxic responses of contaminants within a mixture in contaminated soil.
      This study evaluated the metabolic response of Eisenia fetida after exposure to
      an array of organic compounds to determine whether contaminant-specific responses
      could be identified. The compounds investigated in contact tests included: two
      pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine,
      estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209)
      and two industrial compounds (nonylphenol and dimethyl phthalate). Control and
      contaminant-exposed metabolic profiles were distinguished using principal
      component analysis and potential contaminant-specific biomarkers of exposure were
      found for several contaminants. These results suggest that NMR-based metabolomics
      offers considerable promise for differentiating between the different toxic modes
      of action (MOA) associated with sub-lethal toxicity to earthworms.

PMID- 21856055
TI  - Dynamics of stigma in abortion work: findings from a pilot study of the Providers
      Share Workshop.
AB  - Abortion is highly stigmatized in the United States. The consequences of stigma
      for abortion providers are not well understood, nor are there published accounts
      of tools to assess or alleviate its burdens. We designed The Providers Share
      Workshop to address this gap. Providers Share is a six-session workshop in which
      abortion providers meet to discuss their experiences, guided by an experienced
      facilitator. Seventeen workers at one US abortion clinic participated in a pilot
      workshop. Sessions were recorded and transcribed, and an iterative process was
      used to identify major themes. Participants highlighted stigma, located in
      cultural discourse, law, politics, communities, institutions (including the
      abortion clinic itself), and relationships with family, friends and patients. All
      faced decisions about disclosure of abortion work. Some chose silence, fearing
      judgment and violence, while others chose disclosure to maintain psychological
      consistency and be a resource to others. Either approach led to painful
      interpersonal disconnections. Speaking in the safe space of the Workshop fostered
      interpersonal connections, and appeared to serve as an effective stigma
      management tool. Participants reflected favorably upon the experience. We
      conclude that the Providers Share Workshop may alleviate some of the burdens of
      abortion stigma, and may be an important intervention in abortion human
      resources. We present a conceptual model of the dynamics of stigma in abortion
      work.

PMID- 21856056
TI  - Ectopic thyroid gland in the mandible: a case report and review.

PMID- 21856058
TI  - Female predominance and effect of gender on unilateral condylar hyperplasia: a
      review and meta-analysis.
AB  - PURPOSE: The objective of this review and meta-analysis was to determine the
      existence and extent of the predominance of women among patients with unilateral
      condylar hyperplasia (UCH). Furthermore, we examined the laterality of UCH in
      women and men from international study populations. MATERIALS AND METHODS: We
      performed a review using a standardized search strategy and meta-analysis.
      RESULTS: We included 10 studies in this review, with a total of 275 UCH patients.
      The meta-analysis showed a clear predominance of female patients in the UCH study
      populations; the pooled proportion of female patients was 0.64 (95% confidence
      interval [CI], 0.58-0.70; n = 275 patients). The pooled percentage of female
      patients with left-sided UCH was 42% (95% CI, 34%-51%; n = 138), whereas 45% (95%
      CI, 33%-57%; n = 74) of male patients had left-sided UCH (P = .69 for female
      patients vs male patients). CONCLUSIONS: Female UCH patients outnumber male UCH
      patients in international study populations; therefore female gender may be
      considered a risk factor for UCH. We found no evidence of an association between
      laterality of UCH and gender: male patients and female patients have an almost
      equal distribution of left- and right-sided UCH.

PMID- 21856057
TI  - Effects of pamidronate on human alveolar osteoblasts in vitro.
AB  - PURPOSE: Administration of bisphosphonates has recently been associated with the
      development of osteonecrotic lesions of the jaw (ONJ). To elucidate the potential
      contributions of osteogenic cells to the development and regeneration of ONJ, we
      have isolated primary cells from human alveolar and long/iliac bones, and
      examined the effects of pamidronate on cell viability, proliferation,
      osteogenesis, and wound healing. MATERIALS AND METHODS: Primary human osteoblasts
      and bone marrow stromal cells were isolated from alveolar and iliac/long bone and
      marrow tissue. Cellular proliferation, alkaline phosphatase activity, apoptosis
      (terminal deoxynucleotidyl transferase dUTP nick end labeling, caspase-3, and 4,6
      diamidino-2-phenylindole dihydrochloride assays) and wound healing in an in vitro
      scratch assay were assessed after exposure to pamidronate at a range of
      clinically relevant doses. RESULTS: Primary alveolar osteoblasts proliferated at
      significantly higher rates than long/iliac bone osteoblasts in vitro. Upon
      exposure of alveolar osteoblasts and long/iliac bone marrow stromal cells to
      pamidronate for more than 72 hours, we have observed significantly decreased cell
      viability, proliferation, osteogenesis, and in vitro wound healing at >=6 * 10(
      5) mol/L pamidronate, with the induction of apoptosis in approximately 20% of
      cell population. CONCLUSIONS: The remodeling activity of alveolar bone, indicated
      by higher proliferation of alveolar osteoblasts, could be negatively affected by
      exposure to high concentrations of pamidronate over extended periods. The absence
      of anabolic effects of pamidronate on alveolar osteoblasts and the induction of
      apoptosis in osteogenic cells could negatively affect bone balance at this site
      and contribute to osteonecrosis of the jaw.

PMID- 21856059
TI  - Leiomyosarcoma of the tongue with multiple metastases: a case report and review
      of literature.
AB  - Leiomyosarcoma of the tongue is an extremely rare malignant mesenchymal neoplasm
      and only 25 cases have been described in the English-language literature, 22 of
      which were primary lesions. A case is presented of a 54-year-old female patient
      diagnosed with primary leiomyosarcoma of the tongue with lung and multiple soft
      tissue metastases. This case is especially unusual because widespread soft tissue
      metastases resulted, involving the lung and skeletal muscle in 3 separate sites.
      Unfortunately, curative treatment was not possible. Chemotherapy using a
      combination of ifosfamide and doxorubicin was, therefore, provided as palliation,
      with a good response after a 3-week cycle of therapy. Currently available
      literature on primary and secondary leiomyosarcoma of the tongue was reviewed for
      a better understanding of this rare mesenchymal neoplasm. To the investigators'
      knowledge, there are no other reported cases in the literature that have
      previously been managed with chemotherapy alone.

PMID- 21856060
TI  - Temporomandibular custom hemijoint replacement prosthesis: prospective clinical
      and kinematic study.
AB  - PURPOSE: To evaluate the clinical and functional outcomes of a custom
      temporomandibular hemijoint fossa/eminence implant prosthesis. MATERIALS AND
      METHODS: This prospective cohort study enrolled patients with osteoarthritis of
      the temporomandibular joint. The primary study variables were pain experience,
      pain intensity, chewing ability, jaw opening, joint noise, and overall
      satisfaction of the surgical outcome at 3, 6, and 13 months after surgery. Pre-
      and postsurgical kinematic analyses measured maximum incisal opening, operated
      and unoperated condyle translations, and mandibular body axis rotation using
      mandibular kinematic data combined with patient-specific computed tomographic
      data. The primary analysis of interest concerned preoperative versus
      postoperative changes. RESULTS: The study sample was composed of 36 subjects
      (mean age, 46 years; 94% female; 40 joints). There were statistically significant
      improvements between pre- and postoperative measurements for each study variable.
      The kinematic data documented preservation or an increase of bilateral condylar
      motion, mandibular axis rotation, and mandibular incisor motion. CONCLUSIONS:
      Temporomandibular joint hemiarthroplasty with a custom metal fossa/eminence
      prosthesis provides satisfactory clinical and functional outcomes when used for
      advanced osteoarthritis in patients with focal joint pain secondary to computed
      tomographically documented joint pathology.

PMID- 21856061
TI  - Radiographic findings in the jaws of patients with neurofibromatosis 1.
AB  - PURPOSE: Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder with
      variable phenotypic expression and an incidence of 1:3,000 worldwide. The
      objective was to characterize the NF1-related radiologic alterations found in the
      jaws of these patients. PATIENTS AND METHODS: In total, 102 patients with NF1
      were included in the present study. Six patients had a plexiform neurofibroma in
      the craniofacial region. RESULTS: Radiologic abnormalities in the jaws were found
      in 29 of 102 patients with NF1, including 6 patients with plexiform neurofibroma
      in the head and neck region. The most common radiologic finding was enlargement
      of the mandibular canal. The most prominent skeletal deformities and alterations
      of varying severity were detected in the jaws of 6 patients with plexiform
      neurofibroma. In these patients, the skeletal deformities were seen on the side
      affected by the tumor and possibly caused by the tumor. In 1 patient, however,
      the skeletal changes were on the opposite side. CONCLUSIONS: Radiologic
      abnormalities were found in 29 of 102 patients. The most significant findings
      were profound deformities of the mandible and maxilla in all 6 patients with
      plexiform neurofibroma, but not in the other patients. The facial bone
      deformities found in young patients did not progress markedly at older ages with
      cessation of the patients' growth.

PMID- 21856062
TI  - Reconstruction of major full cheek defects with combined extensive pedicled
      supraclavicular fasciocutaneous island flaps and extended vertical lower
      trapezius island myocutaneous flaps after ablation of advanced oral cancer.
AB  - PURPOSE: The present clinical study assessed the feasibility of extensive
      pedicled supraclavicular fasciocutaneous island flaps combined with extended
      vertical lower trapezius island myocutaneous flaps for large, full-thickness
      cheek defect reconstruction after ablative oral cancer surgery. PATIENTS AND
      METHODS: A retrospective review of data from consecutive patients requiring
      extensive pedicled supraclavicular fasciocutaneous island flaps and the extended
      vertical lower trapezius island myocutaneous flap to provide both an inner and an
      outer lining for major full-thickness cheek defects after oncologic resection.
      RESULTS: Eight patients had advanced oral squamous cell carcinoma. All patients
      had combined bone and extensive soft-tissue defects. The extensive pedicled
      supraclavicular fasciocutaneous island flap with a skin paddle measuring 10 * 8
      cm to 14 * 10 cm and the extended vertical lower trapezius island myocutaneous
      flap with a skin paddle measuring 25 * 10 cm to 15 * 8 cm were used to
      reconstruct the major through-and-through defects. No major complications
      occurred in any patient. The patients were followed up for 6 to 20 months; 6
      patients were living with no evidence of disease, 1 was living with disease, and
      1 had died of local recurrence. CONCLUSIONS: The combined use of the extensive
      pedicled supraclavicular fasciocutaneous island flap with an extended vertical
      lower trapezius island myocutaneous flap to reconstruct major through-and-through
      cheek soft defects is reliable and an excellent alternative to other pedicles,
      even microsurgical free flaps, for patients who have previously undergone
      radiotherapy and surgery of the head and neck.

PMID- 21856063
TI  - Effects of the global and local attention on the processing of categorical and
      coordinate spatial relations.
AB  - Participants made categorical or coordinate spatial judgments on the global or
      local elements of shapes. Stimuli were composed of a horizontal line and two
      dots. In the Categorical task, participants judged whether the line was above or
      below the dots. In the Coordinate task, they judged whether the line would fit
      between the dots. Stimuli were made hierarchical so that the global patterns
      composed of a "global line" made of local dots-and-line units, and "global dot"
      made of a single dots-and-line unit. The results indicated that the categorical
      task was better performed when participants attended to the local level of the
      hierarchical stimuli. On the other hand, the coordinate task was better performed
      when they attended to the global level. These findings are consistent with
      computer simulation models of the attentional modulation of neuronal receptive
      fields' size suggesting that (1) coordinate spatial relations are more
      efficiently encoded when one attends to a relatively large region of space,
      whereas (2) categorical spatial relations are more efficiently encoded when one
      attends to a relatively small region of space.

PMID- 21856064
TI  - Maternal sensitivity and overt aggression in young children with Down syndrome.
AB  - Children with genetic syndromes offer a unique opportunity to combine genetic and
      environmental approaches to the study of aggression. Children with genetic
      syndromes associated with developmental delay are at increased risk for behavior
      problems, but little is known about risk and resilience factors. In this study,
      we examined maternal sensitivity of mothers of children with Down syndrome using
      home observations when their children were 2, 3, and 5 years old, and relations
      with maternal reports and observations of overt aggression at school at age 5.
      Maternal sensitivity at ages 2 and 3 years did not significantly predict child
      aggression at age 5, but low maternal sensitivity at age 5 was significantly
      related to overt aggression at both home and school. By replicating and extending
      earlier work, this study informs developmental theory and identifies an important
      maternal variable related to aggression in children with Down syndrome.

PMID- 21856065
TI  - Adsorptive removal of Cd(II) and Pb(II) ions from aqueous solutions by using
      Turkish illitic clay.
AB  - The ability of Turkish illitic clay (TIC) in removal of Cd(II) and Pb(II) ions
      from aqueous solutions has been examined in a batch adsorption process with
      respect to several experimental conditions including initial solution pH, contact
      time, initial metal ions concentration, temperature, ionic strength, and TIC
      concentration, etc. The characterization of TIC was performed by using FTIR, XRD
      and XRF techniques. The maximum uptake of Cd(II) (11.25 mg g(-1)) and Pb(II)
      (238.98 mg g(-1)) was observed when used 1.0 g L(-1) of TIC suspension, 50 mg L(
      1) of initial Cd(II) and 250 mg L(-1) of initial Pb(II) concentration at initial
      pH 4.0 and contact time of 240 min at room temperature. The experimental data
      were analyzed by the Langmuir, Freundlich, Temkin and Dubinin Radushkevich (D-R)
      isotherm models. The monolayer adsorption capacity of TIC was found to be 13.09
      mg g(-1) and 53.76 mg g(-1) for Cd(II) and Pb(II) ions, respectively. The
      kinetics of the adsorption was tested using pseudo-first-order, pseudo-second
      order, Elovich and intraparticle diffusion models. The results showed that the
      adsorption of Cd(II) and Pb(II) ions onto TIC proceeds according to the pseudo
      second-order model. Thermodynamic parameters including the Gibbs free energy
      (DeltaG), enthalpy (DeltaH), and entropy (DeltaS) changes indicated that the
      present adsorption process was feasible, spontaneous and endothermic in the
      temperature range of 5-40  degrees C.

PMID- 21856066
TI  - Assessing the impacts of mountain biking and hiking on subalpine grassland in
      Australia using an experimental protocol.
AB  - Mountain biking is an increasingly popular, but sometimes controversial, activity
      in protected areas. Limited research on its impacts, including studies comparing
      biking with hiking, contributes to the challenges for mangers in assessing its
      appropriateness. The impacts of mountain bike riding off trail were compared to
      those of hiking on subalpine grassland in Australia using a modification of a
      common trampling experimental methodology. Vegetation and soil parameters were
      measured immediately and two weeks after different intensities of mountain biking
      (none, 25, 75, 200 and 500 passes across slope, 200 pass up and down slope) and
      hiking (200 and 500 passes across slope). There were reductions in vegetation
      height, cover and species richness, as well as changes in species composition and
      increases in litter and soil compaction with riding. Riding up and down a
      moderate slope had a greater impact than riding across the slope. Hiking also
      affected vegetation height, cover and composition. Mountain biking caused more
      damage than hiking but only at high use (500 passes). Further research including
      other ecosystems, topography, styles of riding, and weather conditions are
      required, but under the conditions tested here, hiking and mountain biking appear
      to be similar in their environmental impacts.

PMID- 21856067
TI  - Cost-benefit analysis of water-reuse projects for environmental purposes: a case
      study for Spanish wastewater treatment plants.
AB  - Water reuse is an emerging and promising non-conventional water resource.
      Feasibility studies are essential tools in the decision making process for the
      implementation of water-reuse projects. However, the methods used to assess
      economic feasibility tend to focus on internal costs, while external impacts are
      relegated to unsubstantiated statements about the advantages of water reuse.
      Using the concept of shadow prices for undesirable outputs of water reclamation,
      the current study developed a theoretical methodology to assess internal and
      external economic impacts. The proposed methodological approach is applied to 13
      wastewater treatment plants in the Valencia region of Spain that reuse effluent
      for environmental purposes. Internal benefit analyses indicated that only a
      proportion of projects were economically viable, while when external benefits are
      incorporated all projects were economically viable. In conclusion, the economic
      feasibility assessments of water-reuse projects should quantitatively evaluate
      economic, environmental and resource availability.

PMID- 21856068
TI  - Imaging-histologic discordance after sonographically guided percutaneous breast
      biopsy: a prospective observational study.
AB  - The objective of this study was to determine the frequency of imaging-histologic
      discordance and to compare the frequency of carcinoma between concordant and
      discordant lesions in sonographically (US)-guided 14-gauge core needle biopsies
      (CNBs). From January 2005 to December 2006, we performed US-guided 14-gauge
      automated CNB on 3339 breast lesions and obtained benign results in 2194 cases.
      Five radiologists prospectively reviewed the pathologic reports in conjunction
      with the imaging. We included a total of 1588 lesions that were either excised (n
      = 658) or followed up for at least 2 years (n = 930) after CNB. We evaluated the
      rate of discordance and the clinical findings for both discordant and concordant
      lesions. We also analyzed the clinical and imaging differences between the
      upgrade and non-upgrade groups. Imaging-histologic discordance was present in 103
      of 1588 (6.5%) lesions. The upgrade rate was 6.8% (7/103) in discordant lesions
      and 0.4% (6/1485) in concordant lesions (p < 0.01). Lesion size, Breast Imaging,
      Reporting and Data System (BI-RADS) category and the presence or absence of
      symptoms was statistically significant between the upgrade and non-upgrade groups
      in discordant cases (p < .05). Imaging-histologic discordance is an indication
      for excision because it has a higher upgrade rate than concordant lesions.

PMID- 21856069
TI  - Intravascular ultrasound area strain imaging used to characterize tissue
      components and assess vulnerability of atherosclerotic plaques in a rabbit model.
AB  - The purpose of this study was to investigate the association of area strain and
      tissue components and vulnerability of atherosclerotic plaques in a rabbit model.
      Forty purebred New Zealand rabbits underwent balloon-induced abdominal aorta
      endothelium injury, then a high-cholesterol diet for 24 weeks. Intravascular
      ultrasound (IVUS) images of abdominal aortas were acquired in situ and two
      consecutive frames near the end-diastole were used to construct an IVUS
      elastogram. Histologic slices matched with corresponding IVUS images were stained
      for fatty and collagen components, smooth muscle cells (SMCs) and macrophages.
      Regions-of-interest (ROIs) in plaques were classified as fibrous, fibro-fatty or
      fatty according to histologic study. Vulnerability indexes of ROIs were
      calculated as (fat + macrophage)/(collagen + SMCs). The area strain of these ROIs
      was calculated by use of an in-house-designed software system with a block
      matching-based algorithm. Area strain was significantly higher in fatty ROIs
      (0.056 +/- 0.003) than in fibrous (0.019 +/- 0.002, p < 0.001) or fibro-fatty
      ROIs (0.033 +/- 0.003, p < 0.001). The sensitivity and specificity of area strain
      for fatty ROIs characterization was 75.0% and 80.2% (area under the curve [AUC]
      0.858, 95% confidence interval [CI] = 0.800-0.916, p < 0.001) and 75.0% and 75.3%
      (AUC 0.859, 95% CI = 0.801-0.917, p < 0.001) for fibrous ROIs, as demonstrated by
      receiver operating characteristic curve analysis. Area strain was positively
      correlated with vulnerability index (r(2) = 0.495, p < 0.001), fatty components
      (r(2) = 0.332, p < 0.001) and macrophage infiltration (r(2) = 0.406, p < 0.001);
      and negatively correlated with collagen and SMC composition (r(2) = 0.115 and
      r(2) = 0.169, p < 0.001, respectively). Area strain calculation with IVUS
      elastography based on digital B-mode analysis is feasible and can be useful for
      tissue characterization and plaque vulnerability assessment.

PMID- 21856070
TI  - A single-ensemble clutter rejection method based on the analytic geometry for
      ultrasound color flow imaging.
AB  - In ultrasound color flow imaging (CFI), the single-ensemble eigen-based filters
      can reject clutter components using each slow-time ensemble individually. They
      have shown excellent spatial adaptability. This article proposes a novel clutter
      rejection method called the single-ensemble geometry filter (SGF), which is
      derived from an analytic geometry perspective. If the transmitted pulse number M
      equals two, the clutter component distribution on a two-dimensional (2-D) plane
      will be similar to a tilted ellipse. Therefore, the direction of the major axis
      of the ellipse can be used as the first principal component of the
      autocorrelation matrix estimated from multiple ensembles. Then the algorithm is
      generalized from 2-D to a higher dimensional space by using linear algebra
      representations of the ellipse. Comparisons have been made with the high-pass
      filter (HPF), the Hankel-singular value decomposition (SVD) filter and the
      recursive eigen-decomposition (RED) method using both simulated and human carotid
      data. Results show that compared with HPF and Hankel-SVD, the proposed filter
      causes less bias on the velocity estimation when the clutter velocity is close to
      that of the blood flow. On the other hand, the proposed filter does not need to
      update the autocorrelation matrix and can achieve better spatial adaptability
      than the RED.

PMID- 21856071
TI  - Ultrasound-guided interventional therapy for recurrent ovarian chocolate cysts.
AB  - The aim of this study was to determine the effectiveness of ultrasound-guided
      interventional therapy in the treatment of postoperative recurrent chocolate
      cysts. The 198 patients enrolled in this study were divided into three groups. In
      group 1, the saline washing group, the cavity of the cyst was washed thoroughly
      with warm saline. In group 2, the ethanol short-time retention group, after
      washing with saline, the cyst was injected with 95% ethanol with a volume of half
      of the fluid aspirated from the cyst. Ten minutes later, the rest of the ethanol
      was aspirated. In group 3, the ethanol retention group, the procedures were the
      same as with the ethanol short-time retention group, except that 95% of the
      ethanol was retained in the cyst. An ultrasound examination was performed in the
      third, sixth and 12th months after therapy. The chocolate cyst cure rate was
      significantly higher in the ethanol retention group (96%, 66/69) than in the
      ethanol short-time retention group (82%, 56/68) and no case was cured in the
      first group (saline washing). We conclude that ultrasound-guided injection and
      95% ethanol retention are an effective therapy for the treatment of postoperative
      recurrent chocolate cysts.

PMID- 21856072
TI  - A novel method for more accurately mapping the surface temperature of ultrasonic
      transducers.
AB  - This paper introduces a novel method for measuring the surface temperature of
      ultrasound transducer membranes and compares it with two standard measurement
      techniques. The surface temperature rise was measured as defined in the IEC
      Standard 60601-2-37. The measurement techniques were (i) thermocouple, (ii)
      thermal camera and (iii) novel infra-red (IR) "micro-sensor." Peak transducer
      surface measurements taken with the thermocouple and thermal camera were -3.7 +/-
      0.7 (95% CI) degrees C and -4.3 +/- 1.8 (95% CI) degrees C, respectively, within
      the limits of the IEC Standard. Measurements taken with the novel IR micro-sensor
      exceeded these limits by 3.3 +/- 0.9 (95% CI) degrees C. The ambiguity between
      our novel method and the standard techniques could have direct patient safety
      implications because the IR micro-sensor measurements were beyond set limits. The
      spatial resolution of the measurement technique is not well defined in the IEC
      Standard and this has to be taken into consideration when selecting which
      measurement technique is used to determine the maximum surface temperature.

PMID- 21856074
TI  - Extracorporeal shock wave therapy in pillar pain after carpal tunnel release: a
      preliminary study.
AB  - "Pillar pain" is a relatively frequent complication after surgical release of the
      median nerve at the wrist. Its etiology still remains unknown although several
      studies highlight a neurogenic inflammation as a possible cause. Pillar pain
      treatment usually includes rest, bracing and physiotherapy, although a
      significant number of patients still complain of painful symptoms two or even
      three years after surgery. The aim of this study was to investigate the efficacy
      of low-energy, flux density-focused extracorporeal shock wave therapy (ESWT) in
      the treatment of pillar pain. We treated 40 consecutive patients with ESWT who
      had pillar pain for at least six months after carpal tunnel release surgery, and
      to our knowledge, this is the first study that describes the use of ESWT for
      treating this condition. Our results show that in all of the treated patients,
      there was a marked improvement: the mean visual analogue scale (VAS) score
      decreased from 6.18 (+/-1.02) to 0.44 (+/-0.63) 120 d after treatment, and
      redness and swelling of the surgical scar had also decreased significantly.

PMID- 21856073
TI  - Dual-mode IVUS transducer for image-guided brain therapy: preliminary
      experiments.
AB  - In this study, we investigated the feasibility of using 3.5-Fr intravascular
      ultrasound (IVUS) catheters for minimally-invasive, image-guided hyperthermia
      treatment of tumors in the brain. Feasibility was demonstrated by: (1) retro
      fitting a commercial 3.5-Fr IVUS catheter with a 5 * 0.5 * 0.22 mm PZT-4
      transducer for 9-MHz imaging and (2) testing an identical transducer for therapy
      potential with 3.3-MHz continuous-wave excitation. The imaging transducer was
      compared with a 9-Fr, 9-MHz ICE catheter when visualizing the post-mortem ovine
      brain and was also used to attempt vascular access to an in vivo porcine brain. A
      net average electrical power input of 700 mW was applied to the therapy
      transducer, producing a temperature rise of +13.5 degrees C at a depth of 1.5 mm
      in live brain tumor tissue in the mouse model. These results suggest that it may
      be feasible to combine the imaging and therapeutic capabilities into a single
      device as a clinically-viable instrument.

PMID- 21856075
TI  - Urinary incontinence symptoms stratification: the devil is in the details.

PMID- 21856076
TI  - Patient-reported body image and cosmesis outcomes following kidney surgery:
      comparison of laparoendoscopic single-site, laparoscopic, and open surgery.
AB  - BACKGROUND: Laparoendoscopic single-site surgery (LESS) is reported to result in
      superior cosmesis versus alternative surgical approaches, based solely on surgeon
      assessment or anecdotal evidence. OBJECTIVE: Evaluate patient-reported body image
      and cosmesis outcomes following kidney surgery. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted a prospective and retrospective observational cohort
      study involving patients who underwent kidney surgery (n=114) via LESS (n=35),
      laparoscopic (n=52), or open (n=27) approaches. Cosmesis was evaluated using a
      comprehensive survey administered >=3 mo postoperatively. MEASUREMENTS: Survey
      components were a body image questionnaire (BIQ) consisting of body image and
      cosmesis subscales, a photo-series questionnaire (PSQ) assessing scar preferences
      after knowledge of scar outcomes for alternative surgical approaches, and query
      of preference for future surgical approach using a trade-off method. Body image,
      cosmesis, and PSQ scales ranged from 5 to 20, 3 to 24, and 1 to 10, respectively.
      RESULTS AND LIMITATIONS: Median BIQ component scores did not significantly differ
      across surgical approaches. Median ratings for the LESS, laparoscopy, and open
      scar photographs were 8, 5, and 5, respectively (p=0.0001). Before viewing
      photographs, median self-scar ratings for LESS, laparoscopy, and open approaches
      were 9, 5, and 6.5, respectively (p=0.02); after photographs, ratings were 9, 7,
      and 7, respectively (p=0.008). Assuming equivalent surgical risk among the
      approaches, overall preference for future LESS, laparoscopy, or open surgery was
      39%, 33%, or 4%, respectively. As theoretical risk of LESS was raised, preference
      for LESS decreased, whereas preference for laparoscopy and open surgery
      increased. Study limitations are a nonrandomized design and the use of a
      nonvalidated scale. CONCLUSIONS: Urologic patients favor LESS cosmesis outcomes
      over those for laparoscopy or open surgery. Considering the superior scar
      satisfaction among LESS patients, who were younger and more likely to be
      undergoing surgery for benign disease, we infer that this demographic most values
      the cosmetic advantages of LESS.

PMID- 21856077
TI  - Validity of four pain intensity rating scales.
AB  - The Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), Verbal Rating
      Scale (VRS), and the Faces Pain Scale-Revised (FPS-R) are among the most commonly
      used measures of pain intensity in clinical and research settings. Although
      evidence supports their validity as measures of pain intensity, few studies have
      compared them with respect to the critical validity criteria of responsivity, and
      no experiment has directly compared all 4 measures in the same study. The current
      study compared the relative validity of VAS, NRS, VRS, and FPS-R for detecting
      differences in painful stimulus intensity and differences between men and women
      in response to experimentally induced pain. One hundred twenty-seven subjects
      underwent four 20-second cold pressor trials with temperature order
      counterbalanced across 1 degrees C, 3 degrees C, 5 degrees C, and 7 degrees C and
      rated pain intensity using all 4 scales. Results showed statistically significant
      differences in pain intensity between temperatures for each scale, with lower
      temperatures resulting in higher pain intensity. The order of responsivity was as
      follows: NRS, VAS, VRS, and FPS-R. However, there were relatively small
      differences in the responsivity between scales. A statistically significant sex
      main effect was also found for the NRS, VRS, and FPS-R. The findings are
      consistent with previous studies supporting the validity of each scale. The most
      support emerged for the NRS as being both (1) most responsive and (2) able to
      detect sex differences in pain intensity. The results also provide support for
      the validity of the scales for use in Portuguese samples.

PMID- 21856078
TI  - The occurrence of Codiostomum struthionis in ostriches (Struthio camelus) of
      different ages and during the dry and rainy seasons at two farms in the State of
      Rio de Janeiro, Brazil.
AB  - Ostriches are susceptible to a wide variety of diseases that can affect their
      commercial breeding. The aim of this study was to identify morphologically
      Codiostomum struthionis and examine its seasonal occurrence among animals of
      three age categories in two commercial farms in Areal and Itaborai, State of Rio
      de Janeiro, Brazil. Fresh fecal samples were collected monthly, from June 2004 to
      May 2006. Eggs per gram of feces (EPG) were counted after centrifugal flotation
      in saturated sugar solutions and infective larvae were evaluated after
      coproculture. A total of 432 fecal samples were collected from three groups
      according to ostrich age: up to 90 days, 91-365 days and over 365 days (adults).
      The dry and rainy seasons were defined according to official meteorological data.
      Typical eggs of the Strongylida order were identified in 242 samples (235 from
      adult ostriches). Once obtained, infective larvae were identified as C.
      struthionis. Adult ostriches exhibited significantly greater numbers of eggs in
      their feces during the rainy season compared to the dry season (p<0.05). In the
      Areal farm, significant (p<0.05) values were found when adults ostriches EPG were
      compared to ostriches up to 90 days and also for ostriches from 91 to 365 days.
      When comparing adult EPGs between the two commercial breeding farms, Areal
      exhibited greater EPGs during both the dry (p=0.0215) and rainy (p=0.0011)
      seasons.

PMID- 21856079
TI  - Detection of Tritrichomonas foetus and Pentatrichomonas hominis in intestinal
      tissue specimens of cats by chromogenic in situ hybridization.
AB  - In this retrospective study 102 cats were analyzed for the presence of
      trichomonads in intestinal tissue sections using chromogenic in situ
      hybridization (CISH). Two intestinal trichomonad species are described in cats:
      Pentatrichomonas hominis and Tritrichomonas foetus. While P. hominis is
      considered a mere commensal, T. foetus has been found to be the causative agent
      of feline large-bowel diarrhea. For the detection of both agents within
      intestinal tissue CISH assays using three different probes were performed. In the
      first CISH run a probe specific for all relevant members of the order
      Trichomonadida (OT probe) was used. In a second CISH run all positive samples
      were further examined on three consecutive tissue sections using the OT probe, a
      probe specific for the family of Tritrichomonadidae (Tritri probe) and a newly
      designed probe specifically detecting P. hominis (Penta hom probe). In total,
      four of the 102 cats were found to be positive with the OT probe. Thereof, one
      cat gave a positive reaction with the P. hominis probe and three cats were
      positive with the T. foetus probe. All Trichomonas-positive cats were pure-bred
      and between 8 and 32 weeks of age. In one cat positive for T. foetus large
      amounts of parasites were found in the gut lumen and invading the intestinal
      mucosa. The species of the detected trichomonads were confirmed by polymerase
      chain reaction and nucleotide sequencing of a part of the 18S ribosomal RNA gene.
      In this study, the usefulness of CISH to detect intestinal trichomonads within
      feline tissue samples was shown. Additionally, the specific detection of P.
      hominis using CISH was established. Generally, it was shown that CISH is well
      suited for detection and differentiation of trichomonosis in retrospective
      studies using tissue samples.

PMID- 21856080
TI  - Electrochemotherapy of chest wall breast cancer recurrence.
AB  - Chest wall breast cancer recurrence after mastectomy is a disease difficult to
      treat. Its incidence varies between 5% and 30% in different subset of patients.
      When possible, radical surgical therapy represents the main treatment approach,
      however when the disease progresses and/or treatments are not successful,
      ulceration, bleeding, lymphedema and psychological distress of progressive
      disease significantly decrease the quality of the remaining life of a patient.
      When surgical excision of chest wall recurrence is not possible, other local
      treatments such as radiotherapy, radiotherapy with hyperthermia, topical
      chemotherapy and electrochemotherapy might be taken into account.
      Electrochemotherapy provides safe, efficient and non-invasive locoregional
      treatment approach for chest wall breast cancer recurrence. Several clinical
      studies have demonstrated high efficacy and a good safety profile of
      electrochemotherapy applied in single or multiple consecutive sessions, till
      clinical response was reached. Electrochemotherapy can be performed either with
      cisplatin injected intratumorally or with bleomycin given intratumorally or
      intravenously. Furthermore, it can be effectively used in heavily pre-treated
      areas, after surgery, radiotherapy or systemic chemotherapy. These are the
      advantages that might demand its use especially in patients with pre-treated
      extensive disease and in frail elderly patients. With development of the
      technology electrochemotherapy could even be suggested as a primary local therapy
      in patients not suitable for surgical removal of the primary tumor.

PMID- 21856081
TI  - Chemoprevention for breast cancer.
AB  - Despite the progress that has been made in breast cancer diagnosis and treatment,
      this disease is still a major health problem, being the most frequently diagnosed
      cancer and the first leading cause of cancer death among women both in developed
      and economically developing countries. In some developed countries incidence rate
      start to decrease from the end of last millennium and this can be explained, at
      least in part, by the decrease in hormone replacement therapy use by post
      menopausal women. Chemoprevention has the potential to be an approach of utmost
      importance to reduce cancer burden at least among high-risk populations.
      Tamoxifen and raloxifene are both indicated for the prevention of breast cancer
      in women at high risk for the development of the disease, although raloxifene may
      have a more favorable adverse-effect profile, causing fewer uterine cancers and
      thromboembolic events. Aromatase inhibitors will most probably become an
      additional prevention treatment option in the near future, in view of the
      promising results observed in adjuvant trials and the interesting results of the
      very recently published first chemoprevention trial using an aromatase
      inhibitor.(2) Despite impressive results in most clinical trials performed to
      date, chemoprevention is still not widely used. Urgently needed are better
      molecular risk models to accurately identify high-risk subjects, new agents with
      a better risk/benefit ratio and validated biomarkers.

PMID- 21856082
TI  - Vasopressin selectively impairs emotion recognition in men.
AB  - The biological mechanisms underlying empathy, the ability to recognize emotions
      and to respond to them appropriately, are only recently becoming better
      understood. This report focuses on the nonapeptide arginine-vasopressin (AVP),
      which plays an important role in modulating social behavior in animals,
      especially promoting aggressive behavior. Towards clarifying the role of AVP in
      human social perception we used the Reading of the Mind in the Eyes Test and
      intranasal administration of AVP to show that AVP leads to a significant decrease
      in emotion recognition. Moreover, when comparing photos of males vs. females, all
      viewed by males, AVP had an effect on gender-matched photos only. Furthermore,
      the effect of AVP was restricted to recognition of negative emotions while
      leaving recognition of positive emotions unaffected. The current report
      emphasizes the selective role of AVP in male emotional perception and empathy, a
      core element in all human social interactions.

PMID- 21856083
TI  - The neuromodulative role of earthing.
AB  - Neuromodulation is a process of inhibition, stimulation, modification and
      regulation or therapeutic alteration of activity, electrically and chemically in
      the peripheral, central or autonomic nervous systems. Direct electric current or
      electric field alternates the function of nervous system. Coupling the human
      organism with the Earth directly or via a wire conductor changes the electric
      potential not only on the surface of the body but also inside it, changing the
      potential of electric environment of the human organism. Earthing refers to a
      direct contact with the Earth with bare feet or contact with the Earth with the
      use of conductive wire attached to the human body during sleeping, or daily
      activities. During earthing this electric potential equals to electric potential
      of the Earth and the value of it depends on location, time, atmospheric
      conditions, moisture of the surface of the Earth. The earthing which changes the
      density of negative charge in electric environment of the human body influences
      physiological processes. Our medical hypothesis states that contact with the
      Earth (earthing) directly or via a conductive wire plays role as a
      neuromodulative factor, probably primary, which enables the nervous system to be
      better adapted to the demands of organism and ambient environment. It helps to
      restore natural, electrical status of the electrical environment of the organism
      and thus the nervous system. Earthing generates immediate changes in
      electroencephalography (EEG), surface electromyography (SEMG), and somato-sensory
      evoked potentials (SSEPs). We hypothesize that earthing through its complex
      action on bioelectrical environment of human organism and alternations in
      electrolyte concentrations regulates correct functioning of the nervous system.
      Earthing significantly influences on the electrical activity of the brain.

PMID- 21856084
TI  - p53 facilitates BH3-only BID nuclear export to induce apoptosis in the
      irrepairable DNA damage response.
AB  - Over the past decade, the BH3-only BID likes p53, has emerged as a central player
      in linking death signals through surface death receptors to the core apoptotic
      mitochondrial pathway and life signals through cell cycle arrest. Recent studies
      indicate that pro-apoptotic activation of BID may be negatively regulated by its
      phosphorylation in response to DNA damage. BID itself plays a role in cell cycle
      checkpoint response, in DNA repair, or in integrating apoptosis and the DNA
      damage response, which indicate BID is a nuclear-cytoplasmic protein. However,
      BID does not have any obvious nuclear localization signals (NLS), and only
      carries nuclear export signals (NES). Mutating BID NES does not affect the
      nuclear exit of BID, suggesting that BID NES does not seem to function as a NES.
      Therefore, BID is transported into the nucleus and its export is probably
      mediated by other NES-carrying proteins. As a well-characterized transcription
      factor, p53 carries typical NLS and NES. Bid is transcriptionally regulated by
      p53, and both can be exported from nucleus to the mitochondria in response to DNA
      damage. Moreover, p53 can, through the interaction with BID in the mitochondria
      to induce apoptosis. Given the above background, we hypothesize that p53
      facilitates BID nuclear export to induce apoptosis in response to irreparable DNA
      damage.

PMID- 21856085
TI  - From selenoprotein to endochondral ossification: a novel mechanism with microRNAs
      potential in bone related diseases?
AB  - Selenium participates the formation of selenoprotein as the form of
      selenocysteine, the active-site residue essential for protein catalytic activity.
      It has been proved that selenium deficiency leads to the abnormality of
      selenoprotein biosynthesis, which may lead to disorders of brain, skeleton
      development and cartilage chondrocyte differentiation. The production of
      selenoproteins is regulated by selenocysteine insertion sequence (SECIS) and
      several trans-acting factors in eukaryotic cells. However, the mechanism of
      posttranscriptional modification of selenoproteins biosynthesis seldom needs to
      be elucidated. Recent evidence indicates that miRNAs are key points in the
      process of endochondral ossification. The hypothesis is that the expression of
      key selenoproteins may regulate directly or indirectly via trans-acting factors
      by miRNAs during skeleton development.

PMID- 21856086
TI  - Atrial natriuretic peptide/natriuretic peptide receptor A (ANP/NPRA) signaling
      pathway: a potential therapeutic target for allergic asthma.
AB  - Allergic asthma is a chronic inflammatory disease of airway and immune disorder
      is an acknowledged mechanism. Numerous data demonstrate Th1/Th2 cells play an
      important role in the development of allergic asthma. Atrial natriuretic peptide
      (ANP) is a multifunctional hormone secreted by cardiac atria, lung, and so forth,
      which has been recognized for several decades due to its general effects on
      cardiovascular system, and natriuretic peptide receptor A (NPRA) is the major
      effecting receptor for ANP. In recent years, more and more studies suggest that
      ANP/NPRA signaling pathway is implicated in modulation of immnue and inflammatory
      reaction. Moreover, there are some reports about significant changes of ANP
      production in peripheral blood from asthmatics in acute exacerbation compared
      with patients during the remission and the healthy. Nevertheless, it is unknown
      that why ANP shows an observable change and what role ANP plays in asthma until
      now. We propose that ANP/NPRA signaling pathway is involved in immune dysfunction
      and airway inflammation of allergic asthma based on our experimental results,
      which suggests ANP/NPRA signaling pathway may be a potential therapeutic target
      for allergic asthma.

PMID- 21856087
TI  - The last two millennias echo-catastrophes are the driving forces for the
      potential genetic advantage mechanisms in celiac disease.
AB  - Many human genes have adapted to the constant threat of exposure to changing
      environmental conditions. Balancing selection is the result of an initial stage
      of positive selection that favors the spread in a population of a new allele
      until selection opposes its fixation and balanced situation is established. It is
      suggested that the disadvantageous celiac patients survived the last two
      millennias echo-catastrophes by adapting to the extreme temperature changes and
      their consequences in Europe. Genetic selective diversity induced by changing
      environment, enabled the celiac population to survive. Such a genetic positive
      selection is represented by the HEF C282Y mutation of hemochromatosis, SH2B3 loci
      and the HLA celiac disease-associated repertoire, enabling the celiac to overcome
      iron deficiency anemia and micro pathogen richness, respectively. The increased
      incidence of those evolutionary events in the celiac patients is a recent
      phenomenon that occurred in the latest era of the modern human history. The
      present hypothesis can shed light on additional selective genetic adaptations,
      echo catastrophe-driven that are at the basis of autoimmune disease-affected
      population survival and current expansion.

PMID- 21856088
TI  - Can migraine prophylaxis prevent acute mountain sickness at high altitude?
AB  - Acute mountain sickness (AMS) develops in people trekking at high altitude. The
      underlying mechanism is vasodilation due to low pressure of oxygen. However,
      individual susceptibility for AMS is unknown, thus, one cannot predict when or to
      whom it happens. Because AMS usually begins with headache, and because
      migraineurs are more vulnerable to AMS, we studied by the literatures review on
      the mechanism and clinical features in common, and assessed the treatment
      modalities for both disorders. This led to us the following hypothesis that,
      migraine prophylaxis may prevent or delay the onset of AMS at high altitude.
      Clinical features of AMS include nausea or vomiting when it progresses. Hypobaric
      hypoxia, dehydration or increased physical exertion trigger or aggravate both
      disorders. In migraine, cerebral vasodilation can happen following alteration of
      neuronal activity, whereas the AMS is associated with peripheral vessel dilation.
      Medications that dilate the vessels worsen both conditions. Acute treatment
      strategies for migraine overlap with to those of AMS, including drugs such as
      vasoconstrictors, or other analgesics. To prevent AMS, adaptation to high
      altitude or pharmacological prophylaxis, i.e., acetazolamide has been
      recommended. This carbonic anhydrase inhibitor lowers serum potassium level, and
      thus stabilizes membrane excitability. Acetazolamide is also effective on
      specific forms of migraine. Taken together, these evidences implicate that
      migraine prophylaxis may prevent or delay the onset of AMS by elevating the
      threshold for high altitude.

PMID- 21856089
TI  - Identification of chemical markers for the sensory shelf-life of saveloy.
AB  - The aroma composition, the microbial composition and the sensory profile were
      measured in sliced saveloy samples packed in modified atmosphere (MA). The main
      objective was to identify aroma compounds with potential as chemical markers to
      identify the sensory changes of saveloy. The 60 aroma compounds isolated from the
      saveloy samples by dynamic headspace extraction and measured by Gas
      Chromatography Mass Spectrometry (GC-MS) were used to model the sensory
      attributes sour&old odour and meaty odour using partial least squares regression
      (PLS). 2- and 3-methylbutanal, 2- and 3-methylbutanol, acetoin and diacetyl were
      found to have the highest impact on both sour&old odour and meaty odour of the
      samples. The results show that these four aroma compounds have high potential as
      chemical markers for the sensory shelf-life of sliced and MA-packed saveloy.

PMID- 21856090
TI  - Effects of high pressure application (400 and 900 MPa) and refrigerated storage
      time on the oxidative stability of sliced skin vacuum packed dry-cured ham.
AB  - The effect of high pressure processing at 400 MPa and 900 MPa on the oxidative
      stability of sliced and vacuum packaged commercial dry-cured ham was determined
      by analyzing the antioxidant enzyme activities, TBARS levels (thiobarbituric acid
      reactive substances), vitamin E content and physicochemical characteristics
      during refrigerated storage for 50 days in different light conditions. In dry
      cured ham pressurized at 400 MPa color changes and sensory analyses were also
      assessed. The high pressure process at 900 MPa produced a decrease in superoxide
      dismutase (SOD) and glutathione peroxidase (GSHPx) activities and increased
      vitamin E content. In contrast, pressurization at 400 MPa, increased SOD
      activity, and showed no effect on vitamin E content and GSHPx activity. In
      general the physicochemical parameters determined (fat, moisture and collagen)
      were unaffected by pressurization. Treatment at 400 MPa increased the
      instrumental color measurement of lightness (L* values, CIELAB). This level of
      pressure also modified the hardness, chewiness, saltiness and color intensity.
      These changes of the sensory attributes in dry-cured ham were significant, but
      small.

PMID- 21856091
TI  - Determination of Vitamin B12 in meat products by RP-HPLC after enrichment and
      purification on an immunoaffinity column.
AB  - A quantitative method for the determination of Vitamin B12 in meat products by RP
      HPLC and UV detection was developed and compared to the reference method
      (microbiological assay, MBA). Vitamin B12 was extracted with 50mM sodium acetate
      buffer in the presence of sodium cyanide. For the quantification of total Vitamin
      B12, it was necessary to release protein-bound Vitamin B12 by pepsin treatment.
      Cyanocobalamin was detected as total Vitamin B12 after purification and
      enrichment on an immunoaffinity column. The calibration with five concentrations
      of Vitamin B12 was linear with a regression coefficient r2>0.99. The method was
      validated at three different concentration levels (5-15 ng/g) with salami showing
      good recovery rates between 80 and 108% and low relative standard deviations
      between 1.50 and 7.26% (n = 6). The detection limit was found to be 2 ng/g. The
      Vitamin B12 levels of 50 meat products measured by the developed procedure were
      similar or significantly lower than those determined by the MBA.

PMID- 21856092
TI  - Effects of diphenyl diselenide on oxidative stress induced by sepsis in rats.
AB  - Sepsis is a potentially deadly complication that can be caused by different
      factors. Actually, it is known that oxidative stress is involved in the
      pathogenesis of sepsis. Thus, the aim of this study was to evaluate the effect of
      diphenyl diselenide (PhSe)(2), an emergent compound, on oxidative stress
      parameters induced by sepsis in rats. Animals were pre-injected with (PhSe)(2) or
      vehicle. Twenty-four hours later, sepsis was induced by cecal ligation puncture
      (CLP). After 12 h, liver was taken for thiobarbituric acid reactive species
      (TBARS) measurement, delta-aminolevunic acid dehydratase (delta-ALA-D), Cu/Zn
      superoxide dismutase (Cu/Zn SOD) and catalase (CAT) activities assay. The sepsis
      increased TBARS, inhibited delta-ALA-D, activated Cu/Zn SOD and had a tendency to
      decrease CAT activity. However, (PhSe)(2) prevented the TBARS formation, but did
      not prevent the inhibition of delta-ALA-D activity in the animals with damage.
      Thus, this study showed that (PhSe)(2) partially prevents the oxidative stress
      induced by sepsis, indicating the potential of this compound as a treatment for
      this pathology. Nevertheless, more tests should be performed to confirm the
      hypothesis suggested here.

PMID- 21856093
TI  - The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by
      tissue microarray.
AB  - The purpose of this investigation was to analyze the immunoexpression of FasL,
      Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin
      fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients,
      including adjacent normal tissues, were included on tissue microarray by
      immunohistochemistry. The tumor and the adjacent normal tissues were positive for
      FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%,
      for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and
      8.3%, respectively. FasL and the FADD from tumor were statistically different in
      relation to the histological type. Cleaved caspase 8 was statistically different
      in relation to clinical stage (p=0.031). The FADD from normal tissue was
      statistically different in relation to age (p=0.039), sex (p=0.055), clinical
      stage (p=0.019), and Fas was different in relation to tumor size (p=0.012). In
      the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and
      FasL and cleaved caspase 3. In the adjacent normal tissue, a correlation was
      observed between FasL and Fas, FasL and FADD. There was no association of another
      marker with sex, age, clinical stage, and survival. Our results suggest that
      these proteins mediate the early extrinsic apoptotic pathway in gastric cancer
      and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently
      binds to death receptor FADD signaling activation of the extrinsic apoptotic
      pathway. In this phase, there was inhibition of caspase 8 and, consequently,
      decreased apoptosis.

PMID- 21856094
TI  - Proton radiotherapy for pediatric Ewing's sarcoma: initial clinical outcomes.
AB  - PURPOSE: Proton radiotherapy (PT) has been prescribed similarly to photon
      radiotherapy to achieve comparable disease control rates at comparable doses. The
      chief advantage of protons in this setting is to reduce acute and late toxicities
      by decreasing the amount of normal tissue irradiated. We report the preliminary
      clinical outcomes including late effects on our pediatric Ewing's sarcoma
      patients treated with PT at the Francis H. Burr Proton Therapy Center at
      Massachusetts General Hospital (Boston, MA). METHODS AND MATERIALS: This was a
      retrospective review of the medical records of 30 children with Ewing's sarcoma
      who were treated with PT between April 2003 and April 2009. RESULTS: A total of
      14 male and 16 female patients with tumors in several anatomic sites were treated
      with PT at a median age of 10 years. The median dose was 54 Gy (relative
      biological effectiveness) with a median follow-up of 38.4 months. The 3-year
      actuarial rates of event-free survival, local control, and overall survival were
      60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild
      to-moderate skin reactions. At the time of writing, the only serious late effects
      have been four hematologic malignancies, which are known risks of topoisomerase
      and anthracyline exposure. CONCLUSIONS: Proton radiotherapy was well tolerated,
      with few adverse events. Longer follow-up is needed to more fully assess tumor
      control and late effects, but the preliminary results are encouraging.

PMID- 21856095
TI  - Molecular analysis and antimicrobial resistance of Salmonella isolates recovered
      from raw meat marketed in the area of "Grand Tunis", Tunisia.
AB  - A total of 315 samples of chicken (60), beef (144), minced meat (56), lamb meat
      (33), merguez (10) and fish (12) were collected from various local outlet stores
      in the area of "Grand Tunis", Tunisia between 2006 and 2008. Salmonella was
      recovered from 80 samples with the highest occurrence in chicken (48.3%) followed
      by beef (29.8%), minced meat (10.7%) and lamb (6.0%). No Salmonella were isolated
      from 12 fish and 10 merguez samples (typical Tunisian sausages). Nine serovars
      were identified among the isolates with the predominance of Salmonella
      Typhimurium (n=25) followed by Salmonella Kentucky (n=14), Salmonella Suberu
      (n=12) and Salmonella Zanzibar (n=11). Isolated Salmonella were characterized by
      serotyping, pulsed-field gel electrophoresis (PFGE) analysis, plasmid content and
      antimicrobial resistance profiling. Sixteen (20.0%) Salmonella isolates displayed
      resistance to ampicillin (13 isolates), streptomycin (five isolates),
      cefoperazone (two isolates), furazolodine (two isolates), with seven of these
      isolates displaying multiple resistance to at least two of these antimicriobal
      agents. PFGE analysis showed homogenous restriction patterns in each serovar.
      Compiled serotyping, PFGE analysis, plasmid profiling and antimicrobial
      resistance data provided additional discrimination.

PMID- 21856096
TI  - Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor
      for antituberculosis drug-induced hepatotoxicity in Tunisian patients with
      tuberculosis.
AB  - SETTING: Antituberculosis drug-induced hepatitis attributed to isoniazide (INH)
      is one of the most prevalent drug-induced liver injuries. INH is metabolized by
      hepatic N-acetyltransferase 2 (NAT2) to form hepatotoxins. AIM: To evaluate
      whether polymorphism of the NAT2 gene was associated with antituberculosis drug
      induced hepatotoxicity in Tunisian patients. METHODS: A total of 66 patients with
      tuberculosis (TB) who received anti-TB treatment were followed prospectively.
      Their NAT2 genotype was determined using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). We identified three single nucleotide
      polymorphisms (SNPs); 481C to T (NAT2*5B), 590G to A (NAT2*6A) and 857G to A
      (NAT2*7B). Univariate analysis and logistic regression analysis were used to
      evaluate the risk factors of isoniazid-induced hepatitis. RESULTS: Fourteen
      patients (21.2%) were diagnosed with anti-TB drug-induced hepatitis. None of the
      rapid acetylators-type patients have expressed serum aminotransferase elevation.
      Among patients with hepatotoxicity, slow acetylators-type patients had a higher
      risk of hepatotoxicity than intermediate acetylators (21.4% vs. 78.6%, P=0.01).
      Statistical analysis revealed that the frequency of a variant diplotypes,
      NAT2*5B/5B and NAT2*6A/6A, were significantly increased in TB patients with
      hepatotoxicity, compared with those without hepatotoxicity (P=0.01, odds ratio
      [OR]=7.6 and P=0.029, OR=15, respectively). By contrast, the frequency of the
      rapid acetylation NAT2*4 allele was significantly lower in TB patients with
      hepatotoxicity than those without hepatotoxicity (P=0.02, OR=0.18). Moreover,
      590G/G genotype was associated with decreased hepatotoxicity (P=0.01); by
      contrast, homozygous point mutation at position 481 and 590 were associated with
      a higher risk of hepatotoxicity (P=0.01). CONCLUSION: Our results suggest that
      the slow-acetylator status of NAT2 is risk factor for INH-induced hepatotoxicity.
      Moreover, diplotypes, NAT2*5B/5B, NAT2*6A/6A, 481T/T and 590A/A, are useful new
      biomarkers for predicting anti-TB drug-induced hepatotoxicity.

PMID- 21856097
TI  - Effects of infectious young stock on results of certification, surveillance and
      control programmes for paratuberculosis in dairy herds.
AB  - In many epidemiological models for paratuberculosis, it is assumed that infected
      young stock (<2 years of age) do not shed Mycobacterium avium subsp.
      paratuberculosis (MAP) before adulthood. If this assumption were true, the
      effective separation of young stock from adult cattle (>= 2 years) would largely
      prevent postnatal infections, provided that uninfected adult cattle are highly
      resistant to infection. However, this assumption is in contrast with observed
      faecal shedding of MAP in young stock. Consequently, this assumption may have
      resulted in an underestimation of the effects of MAP transmission in herds
      participating in certification-, surveillance-, and control programmes for
      paratuberculosis. Therefore, the aim of the present study was to evaluate the
      long-term effects of transmission of MAP amongst young stock on key output
      parameters of certification-, surveillance-, and control programmes for
      paratuberculosis in simulated closed dairy herds. Closed Dutch dairy herds
      participating in a paratuberculosis programme were simulated with a stochastic
      model, JohneSSim. Various test schemes, preventive management measures,
      distributions of age at onset of faecal shedding and rates of effective contacts
      between young stock were simulated. The results indicate that transmission of MAP
      amongst young stock has no relevant effects on the animal-level prevalence and
      milk quality of herds that are certified in a paratuberculosis programme.
      However, transmission of MAP amongst young stock increased the economic losses
      due to paratuberculosis and costs of participation in a programme. Moreover, it
      substantially decreased the beneficial effect of the separation of young stock
      from adult cattle on the probability of being certified. However, even in the
      presence of transmission of MAP amongst young stock, preventive management
      measures to separate young stock from adult cattle remain important.

PMID- 21856098
TI  - Antibiotic resistance, phylogenetic grouping and virulence potential of
      Escherichia coli isolated from the faeces of intensively farmed and free range
      poultry.
AB  - Antibiotic use in poultry production is a risk factor for promoting the emergence
      of resistant Escherichia coli. To ascertain differences in different classes of
      chickens, the resistance profile, some virulence genes and phylogenetic grouping
      on 251 E. coli isolates from intensive meat (free range and indoor commercial)
      and free range egg layer chickens collected between December 2008 and June 2009
      in South Australia were performed. Among the 251 strains, 102 (40.6%) and 67
      (26.7%) were found to be resistant to tetracycline and ampicillin respectively.
      Resistance was also observed to trimethoprim-sulfamethoxazole (12.4%),
      streptomycin (10.8%), spectinomycin (9.6%), neomycin (6.0%) and florfenicol
      (2.0%) but no resistance was found to ceftiofur, ciprofloxacin or gentamicin.
      Amplification of DNA of the isolates by polymerase chain reaction revealed the
      presence of genes that code for resistant determinants: tetracycline (tet(A),
      tet(B) and tet(C)), ampicillin (bla(TEM) and bla(SHV)), trimethoprim (dhfrV and
      dhfrXIII), sulphonamide (sulI and sulII), neomycin (aph(3)-Ia(aphA1)), and
      spectinomycin-streptinomycin (aadA2). In addition, 32.3-39.4% of the isolates
      were found to belong to commensal groups (A and B1) and 11.2-17.1% belonged to
      the virulent groups (B2 and D). Among the 251 E. coli isolates, 25 (10.0%)
      carried two or more virulence genes typical of Extraintestinal pathogenic E. coli
      (ExPEC). Furthermore, 17 of the isolates with multi-resistance were identified to
      be groups B2 and D. Although no significant difference was observed between
      isolates from free range and indoor commercial meat chickens (P>0.05),
      significant differences was observed between the different classes of meat
      chickens (free range and indoor commercial) and egg layers (P<0.05). While this
      study assessed the presence of a limited number of virulence genes, our study re
      emphasises the zoonotic potential of poultry E. coli isolates.

PMID- 21856099
TI  - Sudden death due to primary atrial neoplasms: report of two cases and review of
      literature.
AB  - Primary cardiac tumours are very uncommon lesions with an estimated incidence of
      less than 0.03% during autoptic examination. Among these, about 75% are benign,
      mainly myxomas. The intracardiac tumours occur over a wide range of ages and can
      progress silently or have many clinical presentations, such as valvular
      dysfunction, cardiac compression and embolic accidents, mostly in case of atrial
      localization. Primary atrial tumours often progress asymptomatically. Sudden
      death could represent the "first symptom" of these pathological findings. Indeed,
      cardiac neoplasms may cause disorders of atrioventricular or intraventricular
      conduction, which are manifested by fatal arrhythmias. Two cases of sudden death
      due to atrial tumours are reported. A complete autoptic examination, with
      histologic and immunohistochemical study of cardiac lesions, confirmed that these
      neoplasms were primary. Very few cases of sudden death due to right atrial
      tumours have been described in forensic literature, a fact which emphasizes their
      rarity.

PMID- 21856100
TI  - Transmesenteric hernia due to double-loop formation in the small intestine: a
      fatal case involving a toddler.
AB  - We report a unique case of transmesenteric hernia resulting in death, which went
      undiagnosed during a recent hospital visit. The victim was a 2.5-year-old girl
      who - with the exception of chronic constipation - had no medical history. One
      night she complained of abdominal pains and was taken to a pediatric hospital
      where doctors performed an abdominal X-ray and echography. No significant
      findings suggesting bowel obstruction (e.g. air-fluid levels or dilation of the
      bowel) were obtained on examinations and bloody feces were not observed in this
      particular episode. As her abdominal pain gradually attenuated, the doctor
      allowed her to return home. A few hours later, she lost consciousness and expired
      despite resuscitation efforts attempted at an emergency hospital. A subsequent
      autopsy revealed that the small bowel had herniated through a defect in the
      mesentery resulting in two consecutive and inversely forming loops, in which each
      loop protruded on either side of the mesentery. This rare morphological anatomy
      seems to have progressed in a two-step process. The girl's mild abdominal pain
      was likely induced by herniation and formation of the first intestinal loop,
      followed by severe shock occurring when the subsequent intestinal segment
      invaginated into the same defect forming the second loop on the opposite side of
      the mesentery. This case illustrates the difficulty of diagnosing transmesenteric
      hernia due to the presentation of unspecific symptoms; especially in infants and
      toddlers. Furthermore, this report demonstrates the value of a complete autopsy
      in cases of sudden and unexpected deaths involving children.

PMID- 21856101
TI  - Auricular surface aging: a blind test of the revised method on historic Italians
      from Sardinia.
AB  - Age determination from human skeletal remains is an important biological
      parameter in both forensic and bioarchaeological contexts. This study presents
      the results of a blind test of the revised auricular surface age estimation
      method proposed by Buckberry and Chamberlain (Am. J. Phys. Anthropol. 119 (2002)
      321-329) on a large sample (n=404) of known sex and age from the Sassari
      collection, housed at the Museum of Anthropology, University of Bologna, Italy.
      Ilia were scored for five features: transverse organization, surface texture,
      microporosity, macroporosity, and apical changes, which combined for a composite
      score. The results indicated that all features and the composite score were
      positively correlated with known age. Composite scores were significantly
      different between the sexes, suggesting that males and females should be treated
      separately. Bias and inaccuracy varied across age intervals. Age tended to be
      overestimated in individuals under age 59 and underestimated for those over age
      60 years. However, the revised method showed improvement over the original
      auricular surface method (Lovejoy et al., Am. J. Phys. Anthropol. 68 (1985) 15
      28), especially for aging older individuals. Considerable variation exists in the
      age ranges derived from composite scores and few significant differences were
      found between age stages, suggesting that fewer stages with wider age ranges may
      be necessary. The independent, quantitative scoring of the surface features makes
      the revised method substantially easier to apply and the method shows significant
      improvement for aging older individuals.

PMID- 21856102
TI  - Contrast media safety-an update.
AB  - The value of contrast agents has for long been documented by their common daily
      use in imaging departments worldwide. In principle, they should be injected and
      leave the body immediately after use in the same condition or undergo natural
      metabolism without making any harm to the patient. However, this is not the case.
      It is of utmost importance to reduce the prevalence to as close as possible to
      zero. This can be done by identifying the patients at risk before administration
      of contrast agents. For acute non-renal adverse reactions, it is also important
      to be prepared for treating them instantly. The current review is a short state
      of the art regarding adverse reactions to contrast agents.

PMID- 21856103
TI  - Electrically enhanced microextraction for highly selective transport of three
      beta-blocker drugs.
AB  - Facilitated transport of three beta-blocker drugs including atenolol (ATE),
      betaxolol (BET) and propranolol (PRO) was investigated under electrical field
      across a supported liquid membrane (SLM) using phosphoric acid derivatives as
      selective ion carriers, dissolved in 2-nitro phenyl octyl ether (NPOE). In the
      presence of di-(2-ethylhexyl) phosphate (DEHP) and tris-(2-ethylhexyl) phosphate
      (TEHP) in the membrane phase, the three beta-blockers showed completely different
      transport behaviors which enabled highly selective separation of the drugs. Each
      beta-blocker migrated from 3 mL of sample solutions, through a thin layer of
      specific organic solvent immobilized in the pores of a porous hollow fiber, and
      into a 15 MUL acidic aqueous acceptor solution present inside the lumen of the
      fiber. The influences of fundamental parameters affecting the transport of target
      drugs including type of ion carrier for selective separation of each drug and its
      concentration in the membrane phase, extraction voltage, time of transport, pH of
      donor and acceptor phases, stirring speed of donor phase and salt effect were
      studied and optimized. After microextraction process, the extracts were analyzed
      by high-performance liquid chromatography with ultraviolet detection. Under
      optimal conditions, ATE was selectively extracted from different saliva samples
      with recovery of 37%, which corresponded to preconcentration factor of 74. A good
      linearity was achieved for calibration curve with a coefficient of determination
      higher than 0.997. Limits of detection and intra-day precision (n=3) were less
      than 2 MUg L(-1) and 8.8%, respectively.

PMID- 21856104
TI  - Discrimination of the seeds of Notopterygium incisum and Notopterygium franchetii
      by validated HPLC-DAD-ESI-MS method and principal component analysis.
AB  - A validated HPLC-DAD-ESI-MS method has been developed to simultaneously quantify
      12 bioactive compounds in the seeds of Notopterygium incisum Ting ex H.T. Chang
      and Notopterygium franchetii H. de Boiss whose rhizomes and roots are widely used
      as traditional Chinese medicine. This method was validated to be sensitive,
      precise and accurate and was applied to evaluate the difference in the chemical
      profiles and contents of these analytes in 37 batches of N. incisum and 31
      batches of N. franchetii samples collected from different locations. Principal
      component analysis showed that the two species were separated into two groups
      obviously. This study established a validated method for identification of the
      authenticity of the seeds of N. incisum and N. franchetii and supplied effective
      guidance for artificial cultivation.

PMID- 21856105
TI  - Simultaneous quantitation of levodopa and 3-O-methyldopa in human plasma by HPLC
      ESI-MS/MS: application for a pharmacokinetic study with a levodopa/benserazide
      formulation.
AB  - A sensitive and simple method was developed for the quantitation of levodopa and
      its metabolite 3-O-methyldopa, in human plasma, after oral administration of
      tablet formulations containing levodopa (200 mg) and benserazide (50 mg). The
      analytes were extracted by a protein precipitation procedure, using carbidopa as
      an internal standard. A mobile phase consisting of 0.2% formic acid and
      acetonitrile (94:6, v/v) was used and chromatographic separation was achieved
      using ACE C(18) column (50 mm*4.6 mm i.d.; 5 MUm particle size). Selected
      reaction monitoring was performed using the fragmentation transitions m/z 198
      >m/z 107, m/z 212->m/z 166 and m/z 227->m/z 181 for levodopa, 3-O-methyldopa and
      carbidopa, respectively. Calibration curves were constructed over the range 50.0
      6000.0 ng/mL for levodopa and 25.0-4000.0 ng/mL for 3-O-methyldopa. The method
      shown to be specific, precise, accurate and provided recovery rates higher than
      85% for all analytes. No matrix effect was detected in the samples. The validated
      method was applied in a pharmacokinetic study with a levodopa/benserazide tablet
      formulation in healthy volunteers.

PMID- 21856106
TI  - Using newly developed multiplex polymerase chain reaction and melting curve
      analysis for detection and discrimination of beta-lactamases in Escherichia coli
      isolates from intensive care patients.
AB  - A total of 78 bacterial strains with known beta-lactamases were used to optimize
      a rapid detection system consisting of multiplex polymerase chain reaction and
      melting curve analysis to amplify and identify blaTEM, blaSHV, and blaCTX-M genes
      in a single reaction. Additionally, to evaluate the applicability of this method,
      32 clinical isolates of Escherichia coli displaying an extended-spectrum beta
      lactamase phenotype from patients hospitalized at intensive care units were
      tested. Results were analyzed by the Rotor-Gene operating software and Rotor-Gene
      ScreenClust HRM Software. The individual melting curves differed by a temperature
      shift or curve shape, according to the presence of beta-lactamase genes. With the
      use of this method and direct sequencing, blaCTX-M-15-like was identified as the
      most prevalent beta-lactamase gene. In conclusion, this novel detection system
      seems to be a suitable tool for rapid detection of present beta-lactamase genes
      and their characterization.

PMID- 21856107
TI  - Diagnosis of congenital toxoplasmosis by polymerase chain reaction on neonatal
      peripheral blood.
AB  - In a cohort of 12 consecutive neonates, polymerase chain reaction (PCR)
      established the diagnosis of 5 of 6 cases of congenital toxoplasmosis and did so
      earlier than serologic methods. We validated that PCR using neonatal peripheral
      blood is a sensitive, rapid, and cost-effective method to affirm the diagnosis of
      previously undiagnosed congenital toxoplasmosis.

PMID- 21856108
TI  - Plasmid-borne vga(A)-encoding gene in methicillin-resistant Staphylococcus aureus
      ST398 recovered from swine and a swine farmer in the United States.
AB  - We report a novel vga(A) detected in 3 methicillin-resistant Staphylococcus
      aureus ST398 recovered from swine and a swine caretaker in the United States.
      Strains were wild type for L3 and L4, but positive for vga(A) and tet(M). vga(A)
      was plasmid-located (ca. 24-kb) and demonstrated mobilization genes upstream and
      a transposase belonging to the IS3 family located downstream.

PMID- 21856109
TI  - The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus
      correlated with increase of vancomycin MIC.
AB  - A total of 559 methicillin-resistant Staphylococcus aureus isolates were
      investigated for heterogeneous vancomycin-intermediate S. aureus (hVISA) by
      population analysis profile area under the curve. Our results suggested that the
      incidence of hVISA increased rapidly when vancomycin MIC shifted from 1 to 2
      MUg/mL, and at vancomycin MIC of 2 MUg/mL, the incidence of hVISA was nearly 40%.

PMID- 21856110
TI  - Pneumoperitoneum after sexual assault in a patient who had hysterectomy 30 years
      ago: case report.
AB  - BACKGROUND: A non-surgical etiology accounts for approximately 10% of cases of
      pneumoperitoneum. However, in the patient with pneumoperitoneum, one must be
      suspicious of the less common non-surgical etiologies, including coitus, to avoid
      unnecessary laparotomy. OBJECTIVES: To report a case of pneumoperitoneum caused
      by coitus during sexual assault in a patient who had a hysterectomy 30 years ago.
      CASE REPORT: The authors present a case of non-surgical pneumoperitoneum after
      sexual assault occurring over 30 years after abdominal hysterectomy. CONCLUSION:
      This case is an important reminder that a thorough sexual and
      gynecologic/obstetrical history is an essential tool in identifying the patient
      who does not require laparotomy.

PMID- 21856111
TI  - The transverse ligament as a landmark for tibial sagittal insertions of the
      anterior cruciate ligament: a cadaveric study.
AB  - PURPOSE: The purpose of this study was to determine the relation between the
      position of the transverse ligament, the anterior edge of the anterior cruciate
      ligament (ACL) tibial footprint, and the center of the ACL tibial insertion. We
      used arthroscopy for localization of the anatomic landmarks, followed by
      insertions of guide pins under direct visualization, and then the position of
      these guide pins was checked on plain lateral radiographs. METHODS: The
      transverse ligament and the anterior aspect of the ACL tibial footprint were
      identified by arthroscopy in 20 unpaired cadaveric knees (10 left and 10 right).
      Guide pins were inserted with tibial ACL adapter drill guides under direct
      observation at the transverse ligament, the anterior aspect of the tibial
      footprint, and the center of tibial insertion of the ACL. Then, plain lateral
      radiographs of specimens were taken. The Amis and Jakob line was used to define
      the attachment of the ACL tibial insertion and the transverse ligament. A
      sagittal percentage of the location of the insertion point was determined and
      calculated from the anterior margin of the tibia in the anteroposterior
      direction. RESULTS: The transverse ligament averaged 21.20% +/- 4.1%, the
      anterior edge of the ACL tibial insertion averaged 21.60% +/- 4.0%, and the
      center of the ACL tibial insertion averaged 40.30% +/- 4.8%. There were similar
      percent variations between the transverse ligament and the anterior edge of the
      ACL tibial insertion, with no significant difference between them (P = .38).
      Intraobserver and interobserver reliability was high, with small standard errors
      of measurement. CONCLUSIONS: This study shows that the transverse ligament
      coincides with the anterior edge of the ACL tibial footprint in the sagittal
      plane. CLINICAL RELEVANCE: The transverse ligament can be considered as a new
      landmark for tibial tunnel positioning during anatomic ACL reconstruction.

PMID- 21856112
TI  - Length and frequency of intraoperative occlusive events with new torsional
      phacoemulsification software.
AB  - PURPOSE: To evaluate the efficiency profile of new torsional phacoemulsification
      software. SETTING: Eye Institute of Utah, Salt Lake City, Utah, USA. DESIGN:
      Comparative case series. METHODS: Routine cataract surgeries were performed using
      standard torsional (Ozil) and new torsional (Ozil IP) software. The new software
      uses occasional pulses of longitudinal energy that are operator specified and
      system controlled to manage potential occlusion. The new software was compared
      with the previous standard software, which did not include this option. The video
      monitor system was recorded in high definition. Measurement of cumulative
      dissipated energy, balanced salt solution use, and amount of time spent in
      occlusion were measured in a frame-by-frame review of the recorded videos. Data
      were categorized for analysis by software group and cataract grade (1 to 4).
      RESULTS: The study comprised 59 eyes that had cataract removal using the new
      torsional software and 59 eyes using the standard torsional software. Cumulative
      dissipated energy was not statistically significantly different between the 2
      groups. Balanced salt solution use, time spent in occlusion, and the mean longest
      continuous occlusion were significantly lower with the new torsional software;
      these differences were greater as the cataract grade increased. CONCLUSIONS: The
      new torsional software significantly decreased occlusion time and balanced salt
      solution use over standard torsional software, particularly with denser
      cataracts. The net result was a relatively better safety cataract surgery
      profile. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
      in any material or method mentioned.

PMID- 21856113
TI  - Recurrent and extensive vascular malformations in a patient with Bannayan--Riley-
      Ruvalcaba syndrome.
AB  - Bannayan--Riley--Ruvalcaba syndrome (BRRS) is a rare, usually autosomal dominant,
      disease associated with the PTEN hamartoma tumor syndrome, and it is clinically
      diagnosed in the presence of the triad of macrocephaly, genital lentiginosis, and
      intestinal polyposis. Vascular malformations, including arteriolovenous shunts,
      arteriovenous anomalies, and arteriovenous fistulae, can also be seen in a subset
      of BRRS patients, varying from local overgrowth of small vessels to large
      aneurysms. The range of these vascular manifestations and the pathophysiology
      behind them are not completely understood. In this case study, we report on a
      patient with BRRS and recurrent vascular malformations of the left lower
      extremity. We also review the current literature, with a specific focus on the
      breadth of vascular malformations and reported care of these BRRS patients. Based
      on the recurrent and sometimes extensive nature of the vascular pathology, it is
      recommended that physicians monitor BRRS patients closely for early detection and
      treatment.

PMID- 21856114
TI  - Correlations of sensory processing and visual organization ability with
      participation in school-aged children with Down syndrome.
AB  - Previous work has highlighted delays and differences in cognitive, language, and
      sensorimotor functions in children diagnosed with Down syndrome (DS). However,
      sensory processing and visual organization abilities have not been well-examined
      in DS to date. This study aimed to investigate the developmental profile of
      sensory processing and visual organization abilities, body functions classified
      by the World Health Organization's ICF model, and their impacts on participation
      in DS to guide research and evidence-based practices. Two hundred and six
      children (101 boys, 105 girls) with DS (age range = 6 years 1 month to 12 years
      10 months; mean age = 8 years 1 month) were assessed on measures of sensory
      processing (Sensory Profile), visual organization ability (Hooper Visual
      Organization Test), and activity participation (Vineland Adaptive Behavior Scale,
      School Function Assessment). Our findings characterized the developmental
      continuum of body functions (sensory processing and visual organization) of
      children with DS, and revealed their correlations with activity participation.
      Interventions focused on improving body functions is needed while stressing the
      acquisition of functional skills that increase participation in age-appropriate
      activities.

PMID- 21856115
TI  - Development of the Preschool Developmental Assessment Scale (PDAS) on children's
      social development.
AB  - This paper aimed to describe the design and development of the social domain of
      the Preschool Developmental Assessment Scale (PDAS), which would be used for
      assessment of preschool children with different developmental disabilities. The
      original version of the social domain consisted of 30 items. Children were asked
      questions about their social development such as their relationship with others,
      understanding of social norms and rules, empathy and perspective taking. The test
      was administered to 324 children, including 240 children from preschools and 84
      children with developmental disabilities. Rasch analysis was conducted, and all
      except one item were within the acceptable range of infit statistics. The revised
      29-item version could well differentiate between children with typical
      development and children with developmental disabilities. It could also
      differentiate between children from different age groups. The revised version was
      estimated to take around 15 min to administer. The social domain of the PDAS was
      found to be a direct, quick yet reliable assessment tool for assessing the social
      development of preschool children.

PMID- 21856116
TI  - Efficacy of atypical antipsychotic medication in the management of behaviour
      problems in children with intellectual disabilities and borderline intelligence:
      a systematic review.
AB  - The use of medications to manage problem behaviours is widespread. However,
      robust evidence to support their use seems to be lacking. The aim was to review
      research evidence into the efficacy of atypical antipsychotic medication in
      managing problem behaviour in children with intellectual disabilities and
      borderline intelligence. A systematic review was conducted for placebo-controlled
      randomised double-blind trials. The included studies (N = 6) showed that
      risperidone was significantly more effective than placebo in managing problem
      behaviours. However, most studies highlighted adverse events primarily somnolence
      and weight gain. There is now some evidence in favour of the use of risperidone.
      However, because of possible adverse events, these medications have to be used
      with caution.

PMID- 21856117
TI  - Beyond matching on the mean in developmental disabilities research.
AB  - The matching of groups is a traditional way to control for confounding variables
      in developmental disabilities research. The equivalency of means across groups is
      routinely checked for these variables, but not the homogeneity of their variances
      or the shapes of their distributions. In the present paper, it is argued that
      group matching can go seriously wrong unless it directly confronts the
      distributional concerns by the use of well-known statistical indices and very
      simple graphical displays of the distributions. The question of the equivalency
      of item response profiles is also addressed since two participants or two groups
      of participants can obtain the same overall score on the matching variable by
      passing different items. In this case, the matching cannot be considered
      satisfactory because of poor concordance between the molar (overall score) and
      molecular (item scores) levels of matching. Angoff's Delta plot method, a
      statistical approach for detecting differential item functioning across small
      groups is described. It is promising as a simple way to prove whole
      test/individual item correspondence and, in addition, a useful tool for making
      post hoc statistical analyses at the item level on the dependent variables.

PMID- 21856118
TI  - Non-geometric echocardiographic indices of ventricular function in patients with
      a Fontan circulation.
AB  - BACKGROUND: Complex anatomy and limited windows complicate echocardiographic
      assessments of ventricular function in Fontan patients. For the Pediatric Heart
      Network Fontan Cross-Sectional Study, data were acquired from which mean
      ventricular pressure change during isovolumetric contraction (dP/dt(ic)), Tei
      index, and maximal systolic annular velocity (S') could be measured. The purpose
      of this study was to compare these nongeometric indices of ventricular function
      to cardiac magnetic resonance (CMR) measurements of ventricular ejection fraction
      (EF). METHODS: Echocardiographic and CMR studies were performed prospectively
      using standardized protocols; measurements were completed by core laboratories.
      Data from both modalities were available from 137 patients. RESULTS: A weak but
      statistically significant correlation was observed between mean dP/dt(ic) and CMR
      derived EF (r = 0.20, P = .022). This correlation was strengthened when preload
      was taken into account (r = 0.30, P = .001). Statistically significant
      correlations did not exist between CMR-derived EF and the Tei index or S'.
      CONCLUSIONS: Among Fontan patients, the correlation between CMR-derived EF and
      nongeometric echocardiographic indices of ventricular function is not strong. Of
      the indices evaluated, however, mean dP/dt(ic) appears to be the best.

PMID- 21856119
TI  - Alternatives for randomization in lifestyle intervention studies in cancer
      patients were not better than conventional randomization.
AB  - OBJECTIVE: Assessing effects of lifestyle interventions in cancer patients has
      some specific challenges. Although randomization is urgently needed for evidence
      based knowledge, sometimes it is difficult to apply conventional randomization
      (i.e., consent preceding randomization and intervention) in daily settings.
      Randomization before seeking consent was proposed by Zelen, and additional
      modifications were proposed since. We discuss four alternatives for conventional
      randomization: single and double randomized consent design, two-stage randomized
      consent design, and the design with consent to postponed information. STUDY
      DESIGN AND SETTING: We considered these designs when designing a study to assess
      the impact of physical activity on cancer-related fatigue and quality of life. We
      tested the modified Zelen design with consent to postponed information in a
      pilot. The design was chosen to prevent drop out of participants in the control
      group because of disappointment about the allocation. RESULTS: The result was a
      low overall participation rate most likely because of perceived lack of
      information by eligible patients and a relatively high dropout in the
      intervention group. CONCLUSION: We conclude that the alternatives were not better
      than conventional randomization.

PMID- 21856120
TI  - Studies with group treatments required special power calculations, allocation
      methods, and statistical analyses.
AB  - OBJECTIVE: In some trials, the intervention is delivered to individuals in
      groups, for example, groups that exercise together. The group structure of such
      trials has to be taken into consideration in the analysis and has an impact on
      the power of the trial. Our aim was to provide optimal methods for the design and
      analysis of such trials. STUDY DESIGN AND SETTING: We described various treatment
      allocation methods and presented a new allocation algorithm: optimal batchwise
      minimization (OBM). We carried out a simulation study to evaluate the performance
      of unrestricted randomization, stratification, permuted block randomization,
      deterministic minimization, and OBM. Furthermore, we described appropriate
      analysis methods and derived a formula to calculate the study size. RESULTS:
      Stratification, deterministic minimization, and OBM had considerably less risk of
      imbalance than unrestricted randomization and permuted block randomization.
      Furthermore, OBM led to unpredictable treatment allocation. The sample size
      calculation and the analysis of the study must be based on a multilevel model
      that takes the group structure of the trial into account. CONCLUSION: Trials
      evaluating interventions that are carried out in subsequent groups require
      adapted treatment allocation, power calculation, and analysis methods. From the
      perspective of obtaining overall balance, we conclude that minimization is the
      method of choice. When the number of prognostic factors is low, stratification is
      an excellent alternative. OBM leads to better balance within the batches, but it
      is more complicated. It is probably most worthwhile in trials with many
      prognostic factors. From the perspective of predictability, a treatment
      allocation method, such as OBM, that allocates several subjects at the same time,
      is superior to other methods because it leads to the lowest possible
      predictability.

PMID- 21856121
TI  - McMaster Premium LiteratUre Service (PLUS) performed well for identifying new
      studies for updated Cochrane reviews.
AB  - OBJECTIVE: We compared the performance of McMaster Premium LiteratUre Service
      (PLUS) and Clinical Queries (CQs) to that of the Cochrane Controlled Trials
      Register, MEDLINE, and EMBASE for locating studies added during an update of
      reviews. STUDY DESIGN AND SETTING: A sample of new studies in updated Cochrane
      systematic reviews was used as a reference standard. Searches were performed for
      each study in each database. Where a new study was not indexed in PLUS, we
      examined the effect on the review of excluding the study. RESULTS: Ninety-eight
      updated Cochrane reviews were identified. For the 87 reviews with a usable meta
      analysis, PLUS contained all new studies for 13 reviews. No statistically
      significant difference between PLUS and non-PLUS new studies was found when ratio
      of odds ratios (RORs) were pooled across 39 reviews (ROR(?/?): 0.99; 95%
      confidence interval: 0.87-1.14). Thirty-five updated reviews had no new studies
      indexed in PLUS, but conclusions were seldom altered by addition of new studies.
      CONCLUSIONS: PLUS included less than a quarter of the new studies in Cochrane
      updates, but most reviews appeared unaffected by the omission of these studies.
      Reviewers should consider adopting PLUS and CQ filters to improve the efficiency
      of keeping their reviews up to date.

PMID- 21856122
TI  - Clear cell carcinoma of the major salivary gland: time for a different approach
      to management?

PMID- 21856123
TI  - Altered regional synchronization in epileptic patients with generalized tonic
      clonic seizures.
AB  - Epilepsy is a common neurological disorder characterized by hyper-synchronous
      abnormalities of neurons. Resting state brain activity measured by fMRI might
      evaluate the synchronization of the disorder. To investigate the alteration of
      the haemodynamic synchronization in epilepsy, resting-state fMRI (RS-fMRI) was
      performed on 25 patients with primarily generalized tonic-clonic seizures (GTCS),
      along with 25 age- and sex-matched healthy subjects. Regional homogeneity (ReHo),
      a measurement of the synchronization of spontaneous RS-fMRI signal oscillations
      within spatially neighboring voxels, was examined. Compared with the healthy
      controls, the patients with GTCS showed bilaterally and symmetrically altered
      ReHo in the cortical and subcortical structures. In addition, a correlation
      analysis of the ReHo measurement versus the epilepsy duration was performed, and
      highly negative correlations were observed in thalamus, insula and the regions
      followed the pattern of 'default' state of brain function. The current findings
      demonstrate that altered regional synchronization of brain activity exists in the
      patients with GTCS during interictal period, and there is potential in utilizing
      the ReHo method in RS-fMRI analyses of epilepsy.

PMID- 21856124
TI  - Fatty acid oxidation and epilepsy.
AB  - The ketogenic diet (KD) is a high-fat and low carbohydrate diet with an
      established efficacy to treat refractory epilepsy. Lipids, particularly fatty
      acids, are nutrients which provide the most important part of the caloric intake
      under the KD. It has been suggested that the 'high-fat' component of the KD plays
      a role in its anticonvulsant properties. It has been shown experimentally that
      polyunsaturated fatty acids alone (PUFA) exhibit anticonvulsant properties. But
      clinical trials in epilepsy using PUFA have failed to show any effect. This
      discrepancy can be explained by recent experimental data. Several experimental
      studies have suggested that PUFA may support the efficacy of the KD. PUFA may
      exhibit anticonvulsant properties via various mechanisms such as a modification
      of the composition of the CNS cell membranes, stimulation of nuclear receptor
      such as PPAR and by attenuating inflammation. Most of these hypotheses have
      evolved from experimental studies. However, it remains necessary to prove the
      role of PUFA in the KD, and therefore, further studies on this subject are
      needed. A better understanding of the underlying mechanisms may lead to the
      design new dietary treatment such as more liberal rules for KD or KD formula with
      a higher efficacy.

PMID- 21856125
TI  - Hypothalamic hormones and metabolism.
AB  - The ketogenic diet is an effective treatment for medically intractable epilepsy
      and may have antiepileptogenic, neuroprotective, and antitumor properties. While
      on a ketogenic diet, the body obtains most of its calories from fat rather than
      carbohydrates. This dramatic change in caloric composition results in a unique
      metabolic state. In turn, these changes in caloric composition and metabolism
      alter some of the neurohormones that participate in the complex neuronal network
      regulating energy homeostasis. Two observed changes are an increase in serum
      leptin and a decrease in serum insulin. These opposing changes in leptin and
      insulin are unique compared to other metabolic stimuli and may modify the
      activity of several cell signaling cascades including phosphoinositidyl-3 kinase
      (PI3K), adenosine monophosphate activated protein kinase (AMPK), and mammalian
      target of rapamycin (mTOR). These cell signaling pathways may mediate the
      anticonvulsant and other beneficial effects of the diet, though the neurohormonal
      changes induced by the ketogenic diet and the physiological consequences of these
      changes remain poorly characterized.

PMID- 21856127
TI  - Ketogenic diets: where do we go from here?
AB  - In 2012, the third biannual international symposium focused on dietary treatments
      for neurologic disorders will be held. Over the next two years between this
      current meeting in Edinburgh and the next (Chicago, USA), it is important to keep
      strong momentum going in order to advance the field. To summarize all the
      discussions and focus efforts, group meetings were held towards the end of the 4
      day symposium to address the critical issues that needed attention in the
      immediate future. Clinical researchers, basic scientists, dietitians, and parents
      discussed their goals and the results are presented in this article.

PMID- 21856126
TI  - The ketogenic diet: what has science taught us?
AB  - Despite intense and growing interest in studying the mechanisms of ketogenic diet
      (KD) action, and recently published studies implicating novel molecular
      interactions with metabolic substrates, there nevertheless remains the pragmatic
      and scientific challenge of sustaining continued research in this field. This is
      in part a consequence of limited research funding and perhaps skepticism
      regarding the ultimate need to understand underlying mechanisms, particularly
      when clinical studies have increasingly validated the efficacy of the KD and its
      variants. After a decade and a half of more concerted laboratory efforts to
      understand KD mechanisms, it would be prudent to ask - what has all this
      scientific research really taught us? In this regard, it is instructive to
      compare and contrast laboratory research in dietary approaches for epilepsy with
      that traditionally used to screen for potential antiepileptic drugs (AEDs). In
      this review, lessons learned from AED development are applied to the more recent
      experimental findings and approaches attempting to link metabolic changes induced
      by the KD to neuronal and network excitability in the brain.

PMID- 21856128
TI  - Dietary therapies: a worldwide phenomenon.
AB  - At the 2010 Global Symposium on the Dietary Treatments for Epilepsy and other
      Disorders held in Edinburgh, there was an opening evening 75-min session to
      highlight the similarities and differences in the use of the ketogenic diet
      worldwide. Speakers from seven distinct regions of the world briefly presented
      their successes as well as challenges in using dietary therapies. Additionally,
      future clinical and research goals for each area were discussed. This article
      summarizes these talks and the use of the ketogenic diet worldwide.

PMID- 21856130
TI  - fMRI fingerprint of unconditioned fear-like behavior in rats exposed to
      trimethylthiazoline.
AB  - Unconditioned fear plays an important yet poorly understood role in anxiety
      disorders, and only few neuroimaging studies have focused on evaluating the
      underlying neuronal mechanisms. In rodents the predator odor trimethylthiazoline
      (TMT), a synthetic component of fox feces, is commonly used to induce states of
      unconditioned fear. In this study, arterial spin labeling-based functional
      magnetic resonance imaging (fMRI) was applied to detect TMT-induced regional
      modulations of neuronal activity in Wistar rats. During TMT exposure the rats
      displayed increased freezing behavior and reduced exploration in the odor
      associated area. Neuronal activity was selectively increased in the dorsal
      periaqueductal gray, superior colliculus and medial thalamus and reduced in the
      median raphe, locus coeruleus, nucleus accumbens shell, ventral tegmental area,
      ventral pallidum and entorhinal piriform cortex. This fMRI fingerprint involving
      distinct neuronal pathways was used to describe a schematic model of fear
      processing. Key brain areas known to underlie fear and anxiety-related autonomic
      and behavioral responses as well as centers of motivational processing were
      identified as being part of this functional circuitry of innate fear. Thus,
      preclinical fMRI studies based on unconditioned fear methods may provide a
      valuable translational approach to better characterize etiological and
      pathological processes underlying anxiety disorders.

PMID- 21856129
TI  - Insomnia is frequent in schizophrenia and associated with night eating and
      obesity.
AB  - BACKGROUND: Sleep difficulties are common in schizophrenia, however these
      complaints are often overshadowed by more prominent clinical concerns. The point
      prevalence of insomnia in this population is not well documented. Poor sleep is
      associated with lower quality of life, impaired cognition, and weight gain.
      OBJECTIVES: The objectives of this study are to evaluate the prevalence of
      insomnia in schizophrenia and to explore the relationship of sleep to cognition,
      quality of life, and clinical variables. METHOD: 175 outpatients with
      schizophrenia or schizoaffective disorder were assessed for insomnia.
      Participants were evaluated for sleep difficulties, sleep patterns, body mass
      index, and psychiatric symptoms. Participants were also administered a brief
      cognitive assessment of processing speed. RESULTS: 44% of the sample currently
      met the criteria for clinical insomnia. An additional 4% were successfully
      treated with medications. Insomnia was associated with depression and was an
      independent predictor of lower quality of life. Insomnia was also associated with
      high rates of night eating and patients with severe insomnia were significantly
      more obese. The type of antipsychotic did not account for the difference in body
      mass index. No difference between group means in cognition was detected, although
      those with severe insomnia did perform least well. CONCLUSION: Clinical insomnia
      in outpatients with schizophrenia is highly prevalent and has a negative impact
      on quality of life and psychiatric symptoms. This study offers additional support
      to the association between poor sleep and higher weight, as well as indicating a
      potential link to night eating in this population. Assessment for sleep
      difficulties should be a routine part of clinical care.

PMID- 21856131
TI  - The effect of niacin on facial blood flow in people with an elevated fear of
      negative evaluation.
AB  - The vasodilator niacin may provoke greater facial flushing and other symptoms of
      anxiety in patients with social anxiety disorder than in non-anxious controls. To
      determine whether this also applies in non-clinical samples, niacin (100mg) or
      placebo was administered double-blind to 33 young adults and flushing was
      investigated in relation to fear of negative evaluation (a cardinal feature of
      social anxiety). Increases in facial blood flow were greater in people with high
      than low fear of negative evaluation in the niacin condition, but were similar in
      both groups in the placebo condition. However, changes in pulse rate and ratings
      of embarrassment, anxiety, blushing and facial heat were similar in both groups
      in both drug conditions. These findings suggest that the facial vessels of people
      with a heightened fear of negative evaluation are particularly responsive to
      niacin under conditions of low anxiety and embarrassment.

PMID- 21856132
TI  - 19F-decoupling of half-integer spin quadrupolar nuclei in solid-state NMR:
      application of frequency-swept decoupling methods.
AB  - In solid-state NMR studies of minerals and ion conductors, quadrupolar nuclei
      like (7)Li, (23)Na or (133)Cs are frequently situated in close proximity to
      fluorine, so that application of (19)F decoupling is beneficial for spectral
      resolution. Here, we compare the decoupling efficiency of various multi-pulse
      decoupling sequences by acquiring (19)F-decoupled (23)Na-NMR spectra of cryolite
      (Na(3)AlF(6)). Whereas the MAS spectrum is only marginally affected by
      application of (19)F decoupling, the 3Q-filtered (23)Na signal is very sensitive
      to it, as the de-phasing caused by the dipolar interaction between sodium and
      fluorine is three-fold magnified. Experimentally, we find that at moderate MAS
      speeds, the decoupling efficiencies of the frequency-swept decoupling schemes
      SW(f)-TPPM and SW(f)-SPINAL are significantly better than the conventional TPPM
      and SPINAL sequences. The frequency-swept sequences are therefore the methods of
      choice for efficient decoupling of quadrupolar nuclei with half-integer spin from
      fluorine.

PMID- 21856133
TI  - Simultaneous determination of uric acid, xanthine and hypoxanthine at
      poly(pyrocatechol violet)/functionalized multi-walled carbon nanotubes composite
      film modified electrode.
AB  - A sensitive and selective electrochemical method was developed for simultaneous
      determination of uric acid (UA), xanthine (XA) and hypoxanthine (HX) based on a
      poly (pyrocatechol violet)/carboxyl functionalized multi-walled carbon nanotubes
      composite film modified electrode. The preparation and basic electrochemical
      performance of the novel composite film modified glassy carbon electrode were
      investigated in details. The electrochemical behaviors of UA, XA and HX at the
      modified electrode were studied by cyclic voltammetry. The results showed that
      this new electrochemical sensor exhibited excellent electrocatalytic activity
      towards the oxidation of the three analytes. The mechanism of catalysis was
      discussed. The anodic peaks of the three species were well defined with lowered
      oxidation potential and enhanced oxidation peak currents, so the modified
      electrode was used for simultaneous voltammetric measurement of UA, XA and HX by
      differential pulse voltammetry. Under the optimum conditions, the detection
      limits were 0.16 MUmol L(-1) for UA, 0.05 MUmol L(-1) for XA and 0.20 MUmol L(-1)
      for HX, respectively (S/N of 3). The proposed method has been successfully
      applied to simultaneous determination of UA, XA and HX in human serum samples.

PMID- 21856134
TI  - Fabrication of highly porous poly (E-caprolactone) fibers for novel tissue
      scaffold via water-bath electrospinning.
AB  - Highly porous fibers were prepared by water-bath electrospinning from pure poly(E
      caprolactone) (PCL), and its blends with methoxy poly(ethylene glycol) (MPEG).
      These fibers were further analyzed by scanning electron microscopy (SEM),
      differential scanning calorimetry (DSC), X-ray diffraction (XRD), and gravimetric
      as well as contact angle measurement. SEM images showed that the fibers diameters
      as well as pores diameter on the fibers were affected by the weight ratio of
      MPEG/PCL. DSC and XRD not only revealed suppression of crystallinity of PCL but
      also indicated the presence of trace amount of MPEG in PCL water-bath collected
      fibers. The potential use of these hydrophilic porous electrospun fibrous mats as
      scaffolding materials was evaluated in vitro using mouse osteoblasts (MC3T3-E1)
      as reference cell lines. Cytotoxicity assessment of the fiber mats indicated that
      the porous electrospun mat containing trace amount of MPEG was nontoxic to the
      cell. Cell culture results showed that porous fibrous mats were good in promoting
      the cell attachment and proliferation. This novel electrospun matrix could be
      used as potential tissue scaffold material.

PMID- 21856135
TI  - Bone marrow stem cells repopulate thyroid in X-ray regeneration in mice.
AB  - The aim of this study was to clarify the regeneration mechanisms of thyroid in
      post-irradiated C57Bl/6 mice chimeric with transgenic green fluorescent protein
      (GFP) positive C57Bl/6 mice after 5 and 7.5Gy X-ray exposures with the aid of
      morphological and immunocytochemical research of GFP-positive cell distribution.
      Cryostat slides of larynxes with thyroid glands were fixed by mixture of cold
      methanol and ethanol, cell nuclei were stained with propidium iodide. After
      immunocytochemical staining the slides of larynx with thyroid gland were
      investigated by means of confocal LSM 5 PASCAL microscope. True GFP nature of
      green signals in tissue slides was confirmed via additional treatment by anti-GFP
      antibody and Texas Red labeled second antibody. Separate GFP-positive cells were
      observed in the walls of follicles and between follicles of chimeric mice 9-10
      months after X-ray exposure. GFP signal was viewed as cytoplasmic droplets and
      within the colloid of follicles. The share of GFP-positive follicles reached
      6.1+/-1.8%. There was also co-localization of GFP signals and positive staining
      for thyroglobulin by monoclonal antibody. As many as 20.8+/-1.8% among all
      propidium iodide positive blood cells and 52.3+/-8.3% among propidium iodide
      positive bone marrow cells were at the same time GFP-positive. In conclusion, the
      results show that the bone marrow stem cells participate in the thyroid gland
      regeneration after 5Gy X-ray exposure.

PMID- 21856136
TI  - Image-guided radiotherapy for rectal cancer: a systematic review.
AB  - Radiotherapy for rectal cancer is becoming more conformal. Both the rectum and
      the mesorectum are mobile structures and the use of image-guided radiotherapy
      techniques may improve treatment delivery. Studies up to 2008 have previously
      been reviewed; rectal motion was mostly studied in bladder and prostate cancer
      cases. Large variations were seen in both the rectal volume and rectal wall
      displacement during the treatment course. We reviewed the literature on primary
      rectal cancer. A systematic review was conducted using Medline and Embase
      databases using the keywords 'rectal, radiotherapy, IGRT, image guided, organ
      motion, internal margin, target shape/volume'. Nine studies looked at both inter-
      and intrafractional motion of the gross tumour volume, rectum, mesorectum and the
      clinical target volume using a variety of imaging modalities. There was
      significant movement in the upper mesorectum. There was a strong relationship
      between rectal filling and mesorectal motion. Differences according to gender and
      body mass index have been reported. One study showed adequate dose to the rectum
      despite rectal motion and deformation. Current margin recipes may not apply to
      deformable structures. Suggested margins for the clinical target volume to
      planning target volume expansion are between 1 and 3.5cm. There may be a role for
      re-imaging and re-planning during a treatment course. From the available data,
      electronic portal imaging devices should continue to be used to match for bony
      anatomy. Additional information on internal motion can be obtained by cone beam
      computer tomography or tomotherapy and if available its use should be considered.
      Individualised anisotropic margins may be required. Further work is required to
      assess the optimal imaging modality, whether to match to bone or soft tissue, and
      to assess if internal motion affects treatment outcome.

PMID- 21856137
TI  - The effect of acrylamide on alpha-naphthyl acetate esterase enzyme in blood
      circulating lymphocytes and gut associated lymphoid tissues in rats.
AB  - The aim of this study is to determine the functional effects of the acrylamide
      (AA) administrated by oral gavage on the peripheral blood lymphocytes (PBL) and
      the Gut Associated Lymphoid Tissue (GALT) in male Sprague-Dawley rats using alpha
      naphthyl acetate esterase (ANAE) demonstration. For this purpose, two separate
      experiments were performed with Sprague Dawley rats. In Experiment-I rats were
      gavaged with 0, 30, 45 and 60 mg/kgb.w. AA for five consecutive days and in
      Experiment-II rats were gavaged with 0, 125, 150, and 175 mg/kg/b.w. AA for
      single oral dose. Animals were sacrificed 24 h after the last treatments in both
      experiments by servical dislocations under ether anaesthesia. Blood samples were
      collected from the heart in heparinized (10 UI heparin/ml(-1) of the blood) tubes
      before sacrification and lymphoid tissue samples from the ileal Peyer's patches
      (IPPs) were taken and processed for histochemical demonstration of ANAE following
      the sacrification. The lymphoid follicles of the IPPs of animals given 125, 150
      and 175 mg/kgb.w. AA were markedly reduced in size. Germinal centres (GCs)
      markedly regressed in AA-treated animals compared with those of controls. ANAE
      positive lymphocyte depletion of IPPs was very prominent in the high doses AA
      treated animals. In the animals treated with 30, 45, and 60 mg/kg b.w. AA, the
      IPPs had similar histology to those of the controls. ANAE-positive peripheral
      blood lymphocyte levels significantly decreased in AA exposed groups in a dose
      dependent manner (p<0.05). In conclusion, AA has detrimental effects on
      peripheral blood lymphocytes (PBL) and the Gut Associated Lymphoid Tissue (GALT)
      in rats.

PMID- 21856138
TI  - Host pathogens. Editorial overview.

PMID- 21856140
TI  - Cardiovascular disease in asthma and COPD: a population-based retrospective cross
      sectional study.
AB  - We conducted a large population-based retrospective cross-sectional study for
      determining the extent of clinically recognized chronic obstructive pulmonary
      disease (COPD) and asthma, and the prevalence of associated cardiovascular
      diseases (CVDs), using information obtained from the Health Search Database (HSD)
      owned by the Italian College of General Practitioners (SIMG). Our study provides
      further evidence that patients with the diagnosis of COPD are at increased
      association with the diagnosis of most CVDs. It also documents that age clusters
      between 35 and 54 years are those at highest association of simultaneous presence
      of the diagnosis of CVD and that of COPD, with a progressive significant
      reduction in older age clusters. Moreover, it shows that the diagnosis of asthma
      is modestly associated with the diagnosis of different CV morbidities.

PMID- 21856141
TI  - Ayahuasca and the process of regulation in Brazil and internationally:
      implications and challenges.
AB  - BACKGROUND: This paper provides a summary and analysis of the regulation of
      ayahuasca in Brazil, from its prohibition in the mid-eighties to the recent
      adoption of CONAD's (Conselho Nacional de Politicas sobre Drogas) 2010
      Resolution, which established a set of rules, norms and ethical principles to be
      applied to religious and ritual uses of ayahuasca. Brazil's regulatory process is
      used as a starting point to explore emerging international regulatory themes as
      various nations respond to the global expansion of the Santo Daime and UDV (Uniao
      do Vegetal) ayahuasca religions. METHODS: The text reviews the primary
      legislative and court documents, academic literature, as well as solicited expert
      opinions. RESULTS: Three prominent themes have emerged internationally. The first
      concerns the scope of international treaties regarding plant-based psychoactive
      substances, as well as the responsibilities of individual nations to adhere to
      said treaties. The second concerns the scope of religious liberty and how to
      determine religious legitimacy. The final theme addresses the potential dangers
      of ayahuasca to health and public safety. CONCLUSION: Over the past 20 years the
      Brazilian ayahuasca religions have established a global presence, with
      congregations in the USA, Canada, Japan, South Africa, Australia, and throughout
      Europe and Latin America. As a result, many nations are faced with the
      predicament of balancing the interests of these religious minorities with the
      international "war on drugs." The regulatory process applied in Brazil
      exemplifies a progressive approach, one which considered issues of anthropology
      and involved representatives of ayahuasca religions, and which provided a degree
      of deference to the principle of religious liberty. The Brazilian process has
      influenced judicial and administrative decisions internationally, and stands as a
      model worthy of further consideration.

PMID- 21856139
TI  - Pathobionts of the gastrointestinal microbiota and inflammatory disease.
AB  - Our immune system is charged with the vital mission of identifying invading
      pathogens and mounting proper inflammatory responses. During the process of
      clearing infections, the immune system often causes considerable tissue damage.
      Conversely, if the target of immunity is a member of the resident microbiota,
      uncontrolled inflammation may lead to host pathology in the absence of infectious
      agents. Recent evidence suggests that several inflammatory disorders may be
      caused by specific bacterial species found in most healthy hosts. Although the
      mechanisms that mediate pathology remain largely unclear, it appears that genetic
      defects and/or environmental factors may predispose mammals to immune-mediated
      diseases triggered by potentially pathogenic symbionts of the microbiota. We have
      termed this class of microbes 'pathobionts', to distinguish them from acquired
      infectious agents. Herein, we explore burgeoning hypotheses that the combination
      of an immunocompromised state with colonization by pathobionts together comprise
      a risk factor for certain inflammatory disorders and gastrointestinal (GI)
      cancer.

PMID- 21856143
TI  - Rare cell chemiluminescence detection based on aptamer-specific capture in
      microfluidic channels.
AB  - An aptamer-based "sandwich" approach combined with the chemiluminescence (CL)
      analysis was developed for the capture and detection of rare cells on a
      microfluidic chip. Aptamers were immobilized on microfluidic channels to achieve
      capture and isolation of the specific cells from a cell mixture. The capture
      efficiency for target cells was more than 70% with the purity greater than 97%,
      when the content of the target cells was between 0.5% and 10% in the initial cell
      mixture. Gold nanoparticles (Au NPs) modified with aptamers were then added in to
      bind on the cells and trigger a CL reaction. A satisfactory linearity of the
      log/log calibration curve between the CL intensity and the number of target cells
      was observed with a low detection limit of 30 target cells in a 3 MUL cell
      mixture. Spiked whole blood samples were also used to verify the practicality of
      the present method. This work demonstrated the potential application of the cheap
      and rapid CL detection into the early diagnosis of cancers.

PMID- 21856144
TI  - MEMS biosensors for detection of methicillin resistant Staphylococcus aureus.
AB  - This review presents the current state of the conventional methods, microfluidic
      based biosensors, and the commercial products used in the detection of
      methicillin resistant Staphylococcus aureus (MRSA), which is one of the most
      important threats of nosocomial infections in many parts of the world. The early
      detection of MRSA in the specimens of the patients is important to enable the
      appropriate treatment, to decrease morbidity and mortality rates, and to manage
      control actions in the healthcare units. Thus, rapid and inexpensive diagnostic
      systems with high sensitivity and specificity are essential to prevent MRSA to be
      an emerging public health threat. The design and fabrication of new diagnostic
      systems necessitates working in collaboration between different disciplines to
      make new challenges in the field of clinical diagnosis and to meet the demands of
      clinicians. It is certain that in the near future, MEMS and nanotechnology based
      detection methods will take the place of current methods in clinical diagnosis.
      The evaluation of new trends for specificity, sensitivity, cost effectiveness,
      disposability, low weight, ease of use, and facile access should be taken into
      consideration.

PMID- 21856145
TI  - Ankle "sprains" during sport activities with normal radiographs: Incidence of
      associated bone and tendon injuries on MRI findings and its clinical impact.
AB  - OBJECTIVES: To evaluate, with magnetic resonance imaging (MRI), the occurrence of
      bone and tendon injuries and their impact on clinical management in athletes with
      ankle trauma during sports activities having normal radiographs and referred to
      the orthopedic department as "ankle sprains". METHODS: This was a prospective
      study of 54 patients. Clinical examination and MR imaging were done in order to
      have an accurate diagnosis and the incidence of those injuries. RESULTS: Nearly
      half of the patients were found to have no ligament injury on MRI. Isolated bone
      bruises and isolated tendon injuries may share the same clinical signs with ankle
      sprains. CONCLUSIONS: MRI-based clinical management has been adjusted for each
      case; beside the Grade 3 ligament injuries and the rare, but difficult to
      diagnose osteochondral lesions of the talus, partial weight bearing or short
      immobilization were offered as treatment modalities for the rest of the patients
      avoiding unnecessary long-term treatments and rehabilitation exercises.

PMID- 21856146
TI  - Partial achilles tendon rupture presenting with giant hematoma; MRI findings of 4
      year follow up.
AB  - In the young population, spontaneous rupture of Achilles tendon is very rare. The
      big hematoma is also rare finding of the Achilles tendon partial rupture. It is
      usually seen with complete rupture. We presented imaging findings of 4 years
      follow up of the spontaneous partial rupture of Achilles tendon presenting with
      giant expanding hematoma and mimicking complete rupture radiologically. We
      discussed the alterations of tendon signal intensity and result of conservative
      therapy after partial rupture with big hematoma in the long term. A 29 year-old
      man, applied with pain and swelling in the retrocalcaneal region of left ankle.
      He did not have chronic metabolic disease. He was not active in physical
      activities. X-ray radiograms were normal. At magnetic resonance images (MRI),
      there was an intratendinous big hematoma, subcutanous fat planes were edematous
      around tendon. The diagnosis was partial rupture and giant hematoma. Hematoma was
      drained. The conservative treatment was applied and his complaints disappeared.
      After treatment, approximately 4 years later, control MRI showed thickened and
      hypointense tendon in all images.

PMID- 21856147
TI  - The aerodynamics of running socks: Reality or rhetoric?
AB  - AIM: The primary objective of this study was to test the aerodynamic properties
      of a selection of running and general sports socks. METHODS AND PROCEDURES:
      Eleven pairs of socks were tested in a specially constructed rig which was
      inserted into a fully calibrated wind tunnel. Wind test speeds included 3, 4, 5,
      6, 12 and 45m/s. RESULTS: There was no significant difference between any of the
      socks tested for their aerodynamic properties. The drag coefficients calculated
      for each sock varied proportionally with the Reynolds number. No particular sock
      was more aerodynamic than any of the socks tested. CONCLUSION: There is no
      evidence that a sock that is "aerodynamically designed" will help an athlete go
      faster. This may be more product rhetoric than reality, and further work is
      justified if such claims are being made.

PMID- 21856148
TI  - Networks, circuits and computation.

PMID- 21856149
TI  - Mandibular conservation in oral cancer.
AB  - Surgery is one of the established modes of initial definitive treatment for a
      majority of oral cancers. Invasion of bony or cartilaginous structures by
      advanced upper aero-digestive tract cancer has been considered an indication for
      primary surgery on the basis of historic experience of poor responsiveness to
      radiation therapy [1]. The mandible is a key structure both in the pathology of
      intra-oral tumours and their surgical management. It bars easy surgical access to
      the oral cavity, yet maintaining its integrity is vital for function and
      cosmesis. Management of tumours that involve or abut the mandible requires
      specific understanding of the pattern of spread and routes of tumour invasion
      into the mandible. This facilitates the employment of mandibular sparing
      approaches like marginal mandibulectomy and mandibulotomy, as opposed to
      segmental or hemimandibulectomy which causes severe functional problems, as the
      mandibular continuity is lost. Accurate preoperative assessment that combines
      clinical examination and imaging along with the understanding of the pattern of
      spread and routes of invasion is essential in deciding the appropriate level and
      extent of mandibular resection in oral squamous cell carcinoma. Studies have
      shown that local control rates achieved with marginal mandibulectomy are
      comparable with that of segmental mandibulectomy. In carefully selected patients,
      marginal mandibulectomy is an oncologically safe procedure to achieve good local
      control and provides a better quality of life. This article aims to review the
      mechanism of spread, evaluation and prognosis of mandibular invasion, various
      techniques and role of mandibular conservation in oral squamous cell carcinoma.

PMID- 21856150
TI  - Activity stabilization of Aspergillus niger and Escherichia coli phytases
      immobilized on allophanic synthetic compounds and montmorillonite nanoclays.
AB  - The aim of this work was to study the stabilization of the activity of two
      commercial microbial phytases (Aspergillus niger and Escherichia coli) after
      immobilization on nanoclays and to establish optimal conditions for their
      immobilization. Synthetic allophane, synthetic iron-coated allophanes and natural
      montmorillonite were chosen as solid supports for phytase immobilization. Phytase
      immobilization patterns at different pH values were strongly dependent on both
      enzyme and support characteristics. After immobilization, the residual activity
      of both phytases was higher under acidic conditions. Immobilization of phytases
      increased their thermal stability and improved resistance to proteolysis,
      particularly on iron-coated allophane (6% iron oxide), which showed activation
      energy (E(a)) and activation enthalpy (DeltaH(#)) similar to free enzymes.
      Montmorillonite as well as allophanic synthetic compounds resulted in a good
      support for immobilization of E. coli phytase, but caused a severe reduction of
      A. niger phytase activity.

PMID- 21856151
TI  - Economic analysis of biomass power generation schemes under renewable energy
      initiative with Renewable Portfolio Standards (RPS) in Korea.
AB  - An economic analysis of biomass power generation was conducted. Two key
      technologies--direct combustion with a steam turbine and gasification with a
      syngas engine--were mainly examined. In view of the present domestic biomass
      infrastructure of Korea, a small and distributed power generation system ranging
      from 0.5 to 5 MW(e) was considered. It was found that gasification with a syngas
      engine becomes more economically feasible as the plant size decreases. Changes in
      the economic feasibilities with and without RPS or heat sales were also
      investigated. A sensitivity analysis of each system was conducted for
      representative parameters. Regarding the cost of electricity generation,
      electrical efficiency and fuel cost significantly affect both direct combustion
      and gasification systems. Regarding the internal rate of return (IRR), the heat
      sales price becomes important for obtaining a higher IRR, followed by power
      generation capacity and electrical efficiency.

PMID- 21856152
TI  - Ethanol yields and cell wall properties in divergently bred switchgrass
      genotypes.
AB  - Genetic modification of herbaceous plant cell walls to increase biofuels yields
      is a primary bioenergy research goal. Using two switchgrass populations developed
      by divergent breeding for ruminant digestibility, the contributions of several
      wall-related factors to ethanol yields was evaluated. Field grown low lignin
      plants significantly out yielded high lignin plants for conversion to ethanol by
      39.1% and extraction of xylans by 12%. However, across all plants analyzed,
      greater than 50% of the variation in ethanol yields was attributable to changes
      in tissue and cell wall architecture, and responses of stem biomass to dilute
      acid pretreatment. Although lignin levels were lower in the most efficiently
      converted genotypes, no apparent correlation were seen in the lignin monomer G/S
      ratios. Plants with higher ethanol yields were associated with an apparent
      decrease in the lignification of the cortical sclerenchyma, and a marked decrease
      in the granularity of the cell walls following dilute-acid pretreatment.

PMID- 21856153
TI  - Dual pro-drugs of 2'-C-methyl guanosine monophosphate as potent and selective
      inhibitors of hepatitis C virus.
AB  - We have previously reported the power of combining a 5'-phosphoramidate ProTide,
      phosphate pro-drug, motif with a 6-methoxy purine pro-drug entity to generate
      highly potent anti-HCV agents, leading to agents in clinical trial. We herein
      extend this work with the disclosure that a variety of alternative 6-substituents
      are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads,
      and in almost every case the ProTide is several orders of magnitude more potent
      than the parent nucleoside. We also demonstrate that these agents act as pro
      drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use
      of hepatocyte cell lysate as an ex vivo model for ProTide metabolism.

PMID- 21856154
TI  - New betulinic acid derivatives as potent proteasome inhibitors.
AB  - In this study, 22 new betulinic acid (BA) derivatives were synthesized and tested
      for their inhibition of the chymotrypsin-like activity of 20S proteasome. From
      the SAR study, we concluded that the C-3 and C-30 positions are the
      pharmacophores for increasing the proteasome inhibition effects, and larger
      lipophilic or aromatic side chains are favored at these positions. Among the BA
      derivatives tested, compounds 13, 20, and 21 showed the best proteasome
      inhibition activity with IC(50) values of 1.42, 1.56, and 1.80 MUM, respectively,
      which are three to fourfold more potent than the proteasome inhibition controls
      LLM-F and lactacystin.

PMID- 21856155
TI  - Identification of potent c-Src inhibitors strongly affecting the proliferation of
      human neuroblastoma cells.
AB  - Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor
      for which no specific FDA-approved treatment is currently available. The tyrosine
      kinase c-Src has been reported to play an important role in the differentiation,
      cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors
      previously found active in NB cell lines (1-3), small modification of the
      original structures almost abolished the Abl activity with a contemporary
      improvement of affinity and specificity for c-Src. Among the synthesized
      compounds, the most potent c-Src inhibitor (10a) showed a very interesting
      antiproliferative activity in SH-SY5Y cells with an IC(50) of 80 nM and a
      favourable ADME profile. A 3D SAR analysis was also attempted and may guide the
      design of more potent c-Src inhibitors as potential agents for NB treatment.

PMID- 21856156
TI  - Selenium hyperaccumulators facilitate selenium-tolerant neighbors via
      phytoenrichment and reduced herbivory.
AB  - BACKGROUND: Soil surrounding selenium (Se) hyperaccumulator plants was shown
      earlier to be enriched in Se, impairing the growth of Se-sensitive plant species.
      Because Se levels in neighbors of hyperaccumulators were higher and Se has been
      shown to protect plants from herbivory, we investigate here the potential
      facilitating effect of Se hyperaccumulators on Se-tolerant neighboring species in
      the field. RESULTS: We measured growth and herbivory of Artemisia ludoviciana and
      Symphyotrichum ericoides as a function of their Se concentration and proximity to
      hyperaccumulators Astragalus bisulcatus and Stanleya pinnata. When growing next
      to hyperaccumulators, A. ludoviciana and S. ericoides contained 10- to 20-fold
      higher Se levels (800-2,000 mg kg(-1) DW) than when growing next to
      nonaccumulators. The roots of both species were predominantly (70%-90%) directed
      toward hyperaccumulator neighbors, not toward other neighbors. Moreover,
      neighbors of hyperaccumulators were 2-fold bigger, showed 2-fold less herbivory
      damage, and harbored 3- to 4-fold fewer arthropods. When used in laboratory
      choice and nonchoice grasshopper herbivory experiments, Se-rich neighbors of
      hyperaccumulators experienced less herbivory and caused higher grasshopper Se
      accumulation (10-fold) and mortality (4-fold). CONCLUSIONS: Enhanced soil Se
      levels around hyperaccumulators can facilitate growth of Se-tolerant plant
      species through reduced herbivory and enhanced growth. This study is the first to
      show facilitation via enrichment with a nonessential element. It is interesting
      that Se enrichment of hyperaccumulator neighbors may affect competition in two
      ways, by reducing growth of Se-sensitive neighbors while facilitating Se-tolerant
      neighbors. Via these competitive and facilitating effects, Se hyperaccumulators
      may affect plant community composition and, consequently, higher trophic levels.

PMID- 21856157
TI  - mmb1p binds mitochondria to dynamic microtubules.
AB  - BACKGROUND: Mitochondria form a dynamic tubular network within the cell. Proper
      mitochondria movement and distribution are critical for their localized function
      in cell metabolism, growth, and survival. In mammalian cells, mechanisms of
      mitochondria positioning appear dependent on the microtubule cytoskeleton, with
      kinesin or dynein motors carrying mitochondria as cargos and distributing them
      throughout the microtubule network. Interestingly, the timescale of microtubule
      dynamics occurs in seconds, and the timescale of mitochondria distribution occurs
      in minutes. How does the cell couple these two time constants? RESULTS: Fission
      yeast also relies on microtubules for mitochondria distribution. We report here a
      new microtubule-dependent but motor-independent mechanism for proper mitochondria
      positioning in fission yeast. We identify the protein mmb1p, which binds to
      mitochondria and microtubules. mmb1p attaches the tubular mitochondria to the
      microtubule lattice at multiple discrete interaction sites. mmb1 deletion causes
      mitochondria to aggregate, with the long-term consequence of defective
      mitochondria distribution and cell death. mmb1p decreases microtubule dynamicity.
      CONCLUSIONS: mmb1p is a new microtubule-mitochondria binding protein. We propose
      that mmb1p acts to couple long-term mitochondria distribution to short-term
      microtubule dynamics by attenuating microtubule dynamics, thus enhancing the
      mitochondria-microtubule interaction time.

PMID- 21856158
TI  - Loading of meiotic cohesin by SCC-2 is required for early processing of DSBs and
      for the DNA damage checkpoint.
AB  - BACKGROUND: Chromosome segregation and the repair of DNA double-strand breaks
      (DSBs) by homologous recombination require cohesin, the protein complex that
      mediates sister chromatid cohesion (SCC). In addition, cohesin is also required
      for the integrity of DNA damage checkpoints in somatic cells, where cohesin
      loading depends on a conserved complex containing the Scc2/Nipbl protein.
      Although cohesin is required for the completion of meiotic recombination, little
      is known about how cohesin promotes the repair of meiotic DSBs and about the
      factors that promote loading of cohesin during meiosis. RESULTS: Here we show
      that during Caenorhabditis elegans meiosis, loading of cohesin requires SCC-2,
      whereas the cohesin-related complexes condensin and SMC-5/6 can be loaded by
      mechanisms independent of both SCC-2 and cohesin. Although the lack of cohesin in
      scc-2 mutants impairs the repair of meiotic DSBs, surprisingly, the persistent
      DNA damage fails to trigger an apoptotic response of the conserved pachytene DNA
      damage checkpoint. Mutants carrying an scc-3 allele that abrogates loading of
      meiotic cohesin are also deficient in the apoptotic response of the pachytene
      checkpoint, and both scc-2 and scc-3 mutants fail to recruit the DNA damage
      sensor 9-1-1 complex onto persistent damage sites during meiosis. Furthermore, we
      show that meiotic cohesin is also required for the timely loading of the RAD-51
      recombinase to irradiation-induced DSBs. CONCLUSIONS: We propose that meiotic
      cohesin promotes DSB processing and recruitment of DNA damage checkpoint
      proteins, thus implicating cohesin in the earliest steps of the DNA damage
      response during meiosis.

PMID- 21856159
TI  - Cortactin controls cell motility and lamellipodial dynamics by regulating ECM
      secretion.
AB  - BACKGROUND: Branched actin assembly is critical for both cell motility and
      membrane trafficking. The branched actin regulator cortactin is generally
      considered to promote cell migration by controlling leading-edge lamellipodial
      dynamics. However, recent reports indicate that lamellipodia are not required for
      cell movement, suggesting an alternate mechanism. RESULTS: Because cortactin also
      regulates membrane trafficking and adhesion dynamics, we hypothesized that
      altered secretion of extracellular matrix (ECM) and/or integrin trafficking might
      underlie motility defects of cortactin-knockdown (KD) cells. Consistent with a
      primary defect in ECM secretion, both motility and lamellipodial defects of
      cortactin-KD cells were fully rescued by plating on increasing concentrations of
      exogenous ECM. Furthermore, cortactin-KD cell speed defects were rescued on cell
      free autocrine ECM produced by control cells, but not on ECM produced by
      cortactin-KD cells. Investigation of the mechanism revealed that whereas
      endocytosed fibronectin (FN) is redeposited at the basal cell surface by control
      cells, cortactin-KD cells exhibit defective FN secretion and abnormal FN
      retention in a late endocytic/lysosomal compartment. Cortactin-KD motility and FN
      deposition defects were phenocopied by KD in control cells of the lysosomal
      fusion regulator synaptotagmin-7. Rescue of cortactin-KD cells by expression of
      cortactin-binding domain mutants revealed that interaction with the Arp2/3
      complex and actin filaments is essential for rescue of both cell motility and
      autocrine ECM secretion phenotypes, whereas binding of SH3-domain partners is not
      required. CONCLUSIONS: Efficient cell motility, promoted by cortactin regulation
      of branched actin networks, involves processing and resecretion of internalized
      ECM from a late endosomal/lysosomal compartment.

PMID- 21856160
TI  - LCS mobile bearing total knee arthroplasty without patellar resurfacing. Does the
      unresurfaced patella affect outcome? Survivorship at a minimum 10-year follow-up.
AB  - BACKGROUND: Patellar resurfacing during total knee arthroplasty (TKA) remains
      controversial. The aim of this study was to evaluate the long-term outcomes of a
      mobile-bearing TKA without patellar resurfacing. METHODS: We assessed the
      outcomes in 503 patients (600 knees) who had cemented LCS (low contact stress)
      mobile bearing TKA without patellar resurfacing at a minimum follow-up of 10
      years. Clinical outcome scores and radiological assessment were used. RESULTS:
      Four knees were revised, two had bearing dislocation and nine patients (1.5%) had
      secondary resurfacing for anterior knee pain. There were no radiolucent lines or
      osteolytic defects on radiographic evaluation. The overall survivorship was 97.8%
      with re-operation for any reason as the endpoint. CONCLUSION: Non-resurfacing of
      the patella does not adversely affect the outcome of the LCS mobile bearing TKA
      at minimum 10 years follow-up.

PMID- 21856161
TI  - De novo design, synthesis and biological evaluation of 1,4-dihydroquinolin-4-ones
      and 1,2,3,4-tetrahydroquinazolin-4-ones as potent kinesin spindle protein (KSP)
      inhibitors.
AB  - Kinesin spindle protein (KSP) inhibitors are a promising class of anticancer
      agents that cause mitotic arrest in cells from a failure to form functional
      bipolar mitotic spindles. Here, we report the design, synthesis and biological
      evaluation of a novel series of 1,4-dihydroquinolin-4-ones and 1,2,3,4
      tetrahydroquinazolin-4-ones using de novo design method. The synthesized compound
      was evaluated and proved to have potent inhibitory activities in the KSP ATPase.
      Compounds 15j and 15p show potent inhibitory activities in cell proliferation
      assays. Preferred compound 15j markedly induced G2/M phase cell cycle arrest with
      characteristic monoastral spindles and subsequent cell death in A549 cells. In
      vivo evaluation of 15j on the growth of transplantable S180 sarcoma in mice
      suggested its therapeutic potential for further development.

PMID- 21856162
TI  - Inhibitory effects of chalcone glycosides isolated from Brassica rapa L.
      'hidabeni' and their synthetic derivatives on LPS-induced NO production in
      microglia.
AB  - Activation of microglia induces the production of various inflammatory mediators
      including nitric oxide (NO), leading to neurodegeneration in many central nervous
      system diseases. In this study, we examined the effects of chalcone glycosides
      isolated from Brassica rapa L. 'hidabeni' on lipopolysaccharide (LPS)-induced NO
      production using rat immortalized microglia HAPI cells. 4'-O-beta-D
      Glucopyranosyl-3',4-dimethoxychalcone (A2) inhibited LPS-induced inducible NO
      synthase (iNOS) expression and NO production. However, A2 did not affect nuclear
      factor-kappaB and mitogen-activated protein kinase pathways. The signal
      transduction and activator of transcription 1 (STAT1), which is activated via
      production of IFN-beta by LPS, is an important transcription factor responsible
      for LPS-induced iNOS expression. A2 suppressed LPS-induced phosphorylation and
      nuclear translocation of STAT1, although it had no effects on LPS-induced IFN
      beta expression. These results indicate that the inhibitory effect of A2 is due
      to the prevention of STAT signaling. Moreover, structure-activity relationship
      studies on newly synthesized 'hidabeni' chalcone derivatives showed that 4'-O
      beta-D-glucopyranosyl-3'-methoxychalcone (A11), which has no functional groups in
      the B-ring, inhibits LPS-induced NO production more potently than A2.

PMID- 21856163
TI  - Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8
      dihydronaphthalenes as human melanin-concentrating hormone receptor 1
      antagonists.
AB  - Human melanin-concentrating hormone receptor 1 (hMCHR1) antagonists are promising
      targets for obesity treatment. We identified the tetrahydronaphthalene derivative
      1a with modest binding affinity for hMCHR1 by screening an in-house G protein
      coupled receptor (GPCR) ligand library. We synthesized a series of 6-aminomethyl
      5,6,7,8-tetrahydronaphthalenes and evaluated their activity as hMCHR1
      antagonists. Modification of the biphenylcarbonylamino group revealed that the
      biphenyl moiety played a crucial role in the interaction of the antagonist with
      the receptor. The stereoselective effect of the chiral center on binding affinity
      generated the novel 6-aminomethyl-7,8-dihydronaphthalene scaffold without a
      chiral center. Optimization of the amino group led to the identification of a
      potent antagonist 2s (4'-fluoro-N-[6-(1-pyrrolidinylmethyl)-7,8-dihydro-2
      naphthalenyl][1,1'-biphenyl]-4-carboxamide), which significantly inhibited the
      nocturnal food intake in rats after oral administration. Pharmacokinetic analysis
      confirmed that 2s had good oral bioavailability and brain penetrance. This
      antagonist appears to be a viable lead compound that can be used to develop a
      promising therapy for obesity.

PMID- 21856164
TI  - Presence of base excision repair enzymes in the wheat aleurone and their
      activation in cells undergoing programmed cell death.
AB  - Cereal aleurone cells are specialized endosperm cells that produce enzymes to
      hydrolyze the starchy endosperm during germination. Aleurone cells can undergo
      programmed cell death (PCD) when incubated in the presence of gibberellic acid
      (GA) in contrast to abscisic acid (ABA) which inhibits the process. The
      progression of PCD in aleurone layer cells of wheat grain is accompanied by an
      increase in deoxyribonuclease (DNase) activities and the internucleosomal
      degradation of nuclear DNA. Reactive oxygen species (ROS) are increased during
      PCD in the aleurone cells owing to the beta-oxidation of triglycerides and
      inhibition of the antioxidant enzymes possibly leading to extensive oxidative
      damage to DNA. ROS generate mainly non-bulky DNA base lesions which are removed
      in the base excision repair (BER) pathway, initiated by the DNA glycosylases. At
      present, very little is known about oxidative DNA damage repair in cereals. Here,
      we study DNA repair in the cell-free extracts of wheat aleurone layer incubated
      or not with phytohormones. We show, for the first time, the presence of 8
      oxoguanine-DNA and ethenoadenine-DNA glycosylase activities in wheat aleurone
      cells. Interestingly, the DNA glycosylase and AP endonuclease activities are
      strongly induced in the presence of GA. Based on these data we propose that GA in
      addition to activation of nuclear DNases also induces the DNA repair activities
      which remove oxidized DNA bases in the BER pathway. Potential roles of the wheat
      DNA glycosylases in GA-induced oligonucleosomal fragmentation of DNA and
      metabolic activation of aleurone layer cells via repair of transcribed regions
      are discussed.

PMID- 21856166
TI  - Management of esophageal perforations: is there a place for a standardized
      approach?

PMID- 21856165
TI  - Kinetin applications alleviate salt stress and improve the antioxidant
      composition of leaf extracts in Salvia officinalis.
AB  - A pot experiment was carried out under glasshouse conditions with common sage
      (Salvia officinalis L.) to investigate the interactive effects of salt stress and
      kinetin on growth attributes and the abundance of pigments, ions, phenolic
      diterpenes and alpha-tocopherol in leaf extracts of this species. The plants were
      subjected to the following four treatments: (i) control (nutrient solution), (ii)
      control + 10 MUM kinetin, (iii) salt stress (nutrient solution + 100 mM NaCl),
      and (iv) salt stress + 10 MUM kinetin. Kinetin was applied as a foliar
      fertilizer. Salt stress reduced water contents, photosynthetic activity and
      pigment contents of sage leaves. In addition, it increased Na(+) contents, and
      reduced those of Ca(2+) and K(+) in leaves. Salt stress reduced carnosic acid and
      12-O-methyl carnosic acid contents in leaves, while it did not affect carnosol
      and alpha-tocopherol contents. Foliar applications of kinetin seemed to
      counterbalance or alleviate the stress symptoms induced by salinity, improving
      ion and pigment contents, while leaf phenolic diterpene (mainly carnosol) and
      alpha-tocopherol contents also increased in both control and NaCl-treated plants;
      still this effect was much more obvious in salt-treated plants. A similar effect
      was also obtained when plants were sprayed with KNO(3) or Ca(NO(3))(2), thus
      suggesting that kinetin effects were at least partly due to an improvement of ion
      homeostasis. Kinetin applications resulted in increased transcript levels of the
      isoprenoid and tocopherol biosynthetic genes, DXPRI and VTE2 and VTE4 in control
      plants, but not in NaCl-treated plants. We conclude that kinetin can alleviate
      the negative impact of salt on sage plants cultivated under arid environments
      with salinity problems.

PMID- 21856167
TI  - Binding and activity of all human alpha interferon subtypes.
AB  - Vertebrates have multiple genes encoding Type I interferons (IFN), for reasons
      that are not fully understood. The Type I IFN appear to bind to the same
      heterodimeric receptor and the subtypes have been shown to have different
      potencies in various experimental systems. To put this concept on a quantitative
      basis, we have determined the binding affinities and rate constants of 12 human
      Alpha-IFN subtypes to isolated interferon receptor chains 1 and 2. Alpha-IFNs
      bind IFNAR1 and IFNAR2 at affinities of 0.5-5 MUM and 0.4-5 nM respectively
      (except for IFN-alpha1 - 220 nM). Additionally we have examined the biological
      activity of these molecules in several antiviral and antiproliferative models.
      Particularly for antiproliferative potency, the binding affinity and activity
      correlate. However, the EC50 values differ significantly (1.5 nM versus 0.1 nM
      for IFN-alpha2 in WISH versus OVCAR cells). For antiviral potency, there are
      several instances where the relationship appears to be more complicated than
      simple binding. These results will serve as a point of reference for further
      understanding of this multiple ligand/receptor system.

PMID- 21856168
TI  - Towards cytoprotection in the peritransplant period.
AB  - As a consequence of ischemia-reperfusion injury of whole organ transplants and
      hypoxia-anoxia of cell transplants, transplantation unavoidably triggers adverse,
      cytodestructive inflammation within the allograft. Interventions that dampen
      adverse inflammation may limit the extent and duration of this injury, and
      preserve tissue function. Moreover, these interventions should create a milieu
      that guides many donor-activated T cells into a tissue-protective phenotype, thus
      promoting graft acceptance or even tolerance. Hence, it is useful, maybe crucial,
      to identify the measures that minimize deleterious consequences of acute and
      chronic inflammation upon allograft. Several therapies that inhibit activity of
      certain proinflammatory cytokines or expression of tissue "danger signals", while
      sustaining or potentially enhancing the expression of tissue-intrinsic anti
      inflammatory and cytoprotective genes, are awaiting clinical trials or are
      already approved for the treatment of immuno-inflammatory disorders. If applied
      in the peritransplant period, such cytoprotective regimens may increase the pool
      of donor organs suitable for transplantation, reduce the overall requirements for
      maintenance immunosuppression and perhaps foster transplant tolerance.

PMID- 21856169
TI  - Challenges and opportunities in targeting the costimulation pathway in solid
      organ transplantation.
AB  - Signaling through the costimulatory pathway is critical in the regulation of T
      cell activation. Abatacept, a selective costimulatory antagonist FDA approved for
      the treatment of moderate to severe rheumatoid arthritis, binds to CD80 and CD86
      on antigen presenting cells, blocking the interaction with CD28 on T cells.
      Belatacept, a second generation CTLA4-Ig with 2 amino acid substitutions, has
      shown considerable promise in clinical transplantation as part of a maintenance
      immunosuppression regimen. This review will summarize the role of costimulation
      in T cell activation, detail the development of costimulation antagonists and
      highlight the pertinent clinical trials completed and ongoing utilizing
      belatacept as part of an immunosuppressive regimen in organ transplantation.

PMID- 21856170
TI  - Time course of stretching-induced changes in mechanomyogram and force
      characteristics.
AB  - To evaluate the time-course of stretching-induced changes in mechanical
      properties of the muscle-tendon unit (MTU), 11 participants (age 22+/-1 yr; body
      mass 77+/-5 kg; stature 1.78+/-0.05 m; mean+/-SD) underwent tetanic electrical
      stimulations of the medial gastrocnemius muscle before and after (up to 2h)
      stretching administration. During contractions, surface electromyogram (EMG),
      mechanomyogram (MMG) and force were recorded simultaneously. From MMG, peak-to
      peak (p-p) and root mean square (RMS) were calculated during the on-phase and
      plateau phase of tetanic contraction, respectively. After stretching: (i) no
      differences were found in EMG parameters; (ii) MMG p-p and slope decreased (-16%
      and -10%, respectively; P<0.05) and remained depressed for the entire recovery
      period; (iii) MMG RMS increased (+20%; P<0.05), returning to pre-stretching
      values within 15 min; and (iv) peak force (pF), with its first (dF/dt) and second
      (d(2)F/dt(2)) derivative, decreased significantly by 32%, 35% and 54%,
      respectively, and remained depressed for the entire recovery period. The lack of
      MMG p-p and pF recovery could be ascribable to a reduced muscle force generating
      capacity due to persisting changes in viscoelastic characteristics of series
      elastic components. The early return of MMG RMS to pre-stretching values suggests
      that changes in viscoelastic parallel components recovered after few minutes.

PMID- 21856171
TI  - No evidence of expertise-related changes in muscle synergies during rowing.
AB  - The purpose of the present study was to determine whether expertise in rowing is
      driven by a specific structure in muscular coordination. We compared seven
      experienced rowers and eight untrained (i.e., inexperienced) subjects during
      rowing on an ergometer. Both surface electromyography activity and mechanical
      patterns (forces exerted at the handle and the foot-stretcher) were recorded
      during a high intensity rowing exercise. A non-negative matrix factorization was
      applied to 23 electromyographic patterns to differentiate muscle synergies.
      Results showed that expertise was not associated with different dimensionality in
      the electromyographic data and that three muscle synergies were sufficient to
      explain the majority of the variance accounted for (i.e., >90% of the total
      variance) in the two populations. The synergies extracted were similar in the two
      populations, with identical functional roles. While the temporal organization of
      the propulsive synergies was very similar, slight differences were found in the
      composition of the muscle synergies (muscle synergy vectors) between the two
      populations. The results suggests that rowing expertise would not require the
      development of novel muscle synergies but would imply intrinsic synergies already
      used in different behaviors. Performance in rowing is more probably linked to
      adjustments in the mechanical output of the muscle synergies rather than to
      differences in the shape and timing of their activations.

PMID- 21856172
TI  - CT fluoroscopy-guided placement of inferior vena cava filters: feasibility study
      in pigs.
AB  - PURPOSE: To evaluate the feasibility of computed tomography (CT)-guided placement
      of inferior vena cava (IVC) filters in a swine model. MATERIALS AND METHODS: Five
      domestic pigs (60-70 kg) underwent transfemoral and transjugular IVC filter
      placement under real-time CT fluoroscopic guidance. Filter position was confirmed
      by contrast-enhanced CT and digital subtraction angiography. Filter tilt,
      distance to target position, and fluoroscopy time were analyzed. RESULTS: A total
      of 10 filters were successfully implanted (five via transfemoral approach, five
      via transjugular approach) without complications. The mean distance to the target
      position was 0.3 cm +/- 0.2. Mean filter tilt was 3.2 degrees  +/- 2.3 (range, 0
      degrees -7 degrees ), without differences between deployment techniques (P =
      .8486). Average fluoroscopy time was 25.9 s +/- 6.9 per procedure. CONCLUSIONS:
      CT fluoroscopy-guided placement of IVC filters is safely feasible. Use of this
      technique may avoid the need to move critically ill patients.

PMID- 21856173
TI  - In vitro design and characterization of the nonviral gene delivery vector
      iopamidol, protamine, ethiodized oil reagent.
AB  - PURPOSE: To demonstrate cellular selectivity toward hepatoma cells and compare
      the efficiency of gene delivery of a novel nonviral vector of iopamidol,
      protamine, and ethiodized oil reagents (VIPER). MATERIALS AND METHODS: Rat
      hepatocellular carcinoma (HCC) cells were transfected in triplicate under varying
      conditions by using firefly luciferase as a reporter gene. Conditions included
      variations of a protamine:DNA (P:D) complex (20:1, 50:1, 100:1, 200:1 mass
      ratios), iopamidol (0%, 10%, 33%), and ethiodized oil (0%, 1%, 2%, 4%, 8%, and
      16%). The conditions affording efficient gene transfer and ease of translation to
      in vivo studies were selected for cell line comparison (HCC cells vs
      hepatocytes). Adenoviral transduction was compared with nonviral vector
      transfection. RESULTS: At low concentrations, ethiodized oil increased
      transfection efficiency regardless of P:D mass ratio. However, high
      concentrations resulted in significant attenuation. Unexpectedly, the addition of
      iopamidol to P:D complexes markedly improved transfection efficiency. When using
      an optimal P:D, iopamidol, and ethiodized oil solution, DNA transfection of
      normal liver and tumor cells showed significant selectivity for tumor cells. In
      the context of hepatoma cells, transfection efficiency with the nonviral vector
      was better than 10(4) pfu adenovirus. CONCLUSIONS: The development and
      characterization of the VIPER system provides a possible alternative to viral
      gene therapy of HCC.

PMID- 21856174
TI  - Cardiopulmonary magnetic resonance imaging in children after lung
      transplantation: preliminary observations.
AB  - BACKGROUND: Lung transplantation carries a guarded prognosis and is burdened by
      short-term and long-term complications that affect the airway, lungs, and
      vasculature. In this pilot study we aimed to assess the feasibility of magnetic
      resonance imaging (MRI) in 8 pediatric patients after lung transplantation.
      METHODS: The 8 patients in the study were aged between 9 and 17 years and were
      clinically stable. The scan protocol included MR angiography, phase contrast
      imaging of the pulmonary arteries and veins, ventricular volumetry, lung
      parenchyma imaging, and lung volumetry. RESULTS: This protocol was successfully
      done in all patients. Lung volumes measured by MRI correlated well with those by
      body plethysmography (r = 0.83, p = 0.01). Angiography detected caliber
      differences between the donor and recipient pulmonary arteries in 5 patients. One
      patient had hemodynamically relevant pulmonary vein stenosis, as evidenced by MR
      angiography, a reduction in ipsilateral flow, and an abnormal pulmonary venous
      flow profile. Three patients had mild left (2 patients) or right (1 patient)
      ventricular systolic dysfunction. One patient had left main bronchus compression,
      and 3 patients showed varying degrees of pleural thickening. CONCLUSIONS: Our
      preliminary experience suggests that cardiopulmonary MRI is feasible in pediatric
      lung transplant recipients and that it provides clinically useful information,
      especially on the vascular and bronchial anastomoses. However, the value of MRI
      for routine follow-up in pediatric lung transplant patients needs to be
      determined in a larger cohort.

PMID- 21856175
TI  - Forearm pain associated with loose radial head prostheses.
AB  - BACKGROUND: After post-traumatic radial head replacement, pain caused by a loose
      prosthesis might incorrectly be assumed to be post-traumatic. Reliable guidelines
      for diagnosing a symptomatic loose radial head prosthesis are lacking. We noted
      that pain from a loose stem within the proximal radius may present as proximal
      radial forearm pain. METHODS: The medical records and radiographs of 14
      consecutive cases (13 patients) with proximal radial forearm pain associated with
      a loose radial head prosthesis were reviewed retrospectively. The indication for
      revision surgery was painful loosening of the prosthesis within the canal of the
      proximal radius in 7 patients (8 cases) and pain without preoperative
      confirmation of the loosening in 2 patients (2 cases). Various prosthetic designs
      had been used in the primary operations. RESULTS: In 12 of 14 cases, the
      loosening was evident radiographically, but in 2 the only indication of a loose
      prosthesis (confirmed surgically) was proximal radial forearm pain. One patient
      was lost to follow-up. Revision or prosthetic removal eliminated the pain in 7 of
      9 cases and decreased it in 1. One patient with moderate pain had an arthritic
      elbow and had no significant lasting relief from surgery. Follow-up averaged 27
      months. CONCLUSION: The presence of proximal radial forearm pain in a patient
      with a radial head prosthesis is an indicator of symptomatic mechanical
      loosening. If the prosthesis has a textured surface for bone ingrowth, and was
      inserted without cement, we now consider this a strong indicator of loosening,
      even in the absence of radiographic signs.

PMID- 21856176
TI  - Effects of rasp mismatch on plasma spray radial head stems.
AB  - BACKGROUND: Radial head prosthetic stems designed for bone ingrowth are available
      with both plasma spray and grit blasted surfaces. A recent study comparing
      micromotion between the 2 demonstrated greater micromotion in the plasma spray
      than grit blasted stems, even though the latter had lower surface roughness. This
      raised the question that perhaps the size mismatch for grit-blasted radial head
      stems (0.5 mm) might be inadequate for plasma spray stems. HYPOTHESIS: A tighter
      initial press-fit with plasma spray radial head stems may be gained by
      preparation with an undersized rasp. METHODS: Paired cadaveric radii were
      implanted with plasma spray stems. The surgical control was prepared with a rasp
      designated for its corresponding stem size ("size-matched"), while the
      experimental group was prepared with a rasp 0.5 mm smaller than designated
      ("undersized"). RESULTS: The micromotion for the undersized rasp group (46 +/- 12
      MUm) was not significantly different than for the size-matched rasp group (21 +/-
      12 MUm) (P = .1). DISCUSSION: Contrary to our hypothesis, no reduction in
      micromotion was observed when using an undersized rasp with a plasma spray stem.
      The micromotion results were not different from those observed when using a size
      matched rasp, and actually approached significance in the opposite direction.
      This may be due to the rough stem surface chipping away bone fragments, rather
      than the bone being cut away precisely as is done with a rasp. CONCLUSION: The
      use of an undersized rasp prior to implantation of a plasma spray radial head
      prosthesis does not confer any added benefit in terms of initial stability.

PMID- 21856177
TI  - Humeral retroversion and its association with posterior capsule thickness in
      collegiate baseball players.
AB  - HYPOTHESIS AND BACKGROUND: Baseball players commonly present with decreases in
      internal rotation (IR) and concurrent increases in external rotation (ER) motion.
      Several glenohumeral (GH) adaptations have been theorized to cause these changes
      in motion, including humeral retroversion (HR) and posterior capsule thickness
      (PCT). However, limited data exist examining the inter-relationship between HR
      and PCT. Therefore, the purpose of this study was to measure HR, GH IR and ER
      rotation, and PCT. MATERIALS AND METHODS: HR and PCT were measured with an
      ultrasound system (Sonosite Titan; Sonosite, Bothell, WA, USA), and GH IR and ER
      were measured with a digital inclinometer. RESULTS: The dominant arm had
      significantly more HR (15.6 degrees , P = .0001) than the nondominant arm.
      Pearson correlation coefficients showed a significant negative relationship
      between HR and GH IR (-0.472, P = .001) and a significant positive relationship
      between HR and GH ER (0.295, P = .042). A significant positive correlation was
      also found between HR and PCT (0.427, P = .003). DISCUSSION: This was the first
      study to identify a relationship between HR and PCT in addition to GH IR and ER.
      The identification of these multiple correlations appears to suggest that the
      loss of IR caused by HR may be placing additional stress on the posterior capsule
      during the deceleration phase of the throw, thereby causing a fibroblastic
      healing response. CONCLUSIONS: HR has previously been identified as a positive
      adaptation because of the increase in ER without anterior capsule attenuation.
      However, this study suggests that HR may be contributing to the negative
      adaptation of PCT.

PMID- 21856178
TI  - Radial head replacement with a bipolar system: a minimum 2-year follow-up.
AB  - BACKGROUND: We report the short-term results of a cohort of patients undergoing
      radial head replacement using a novel radial head prosthesis with a smooth,
      unfixed, telescoping stem and a bipolar design after a mean follow-up of 34
      months (range, 24-48 months). MATERIALS AND METHODS: Patients were assessed using
      clinical and radiographic examination as well as with standardized outcome
      measures. Thirty implants (29 patients) were available for review. RESULTS: At
      final follow-up, the average Mayo Elbow Performance Index Score was 92.1 and the
      Disabilities of the Arm, Shoulder, and Hand Score was 13.8. Clinical examination
      revealed significant differences between operative and nonoperative sides for
      flexion/extension and pronation/supination. Radiographic measurement of medial
      and lateral ulnohumeral spaces revealed re-establishment of a congruent elbow
      joint. No significant arthritic changes were identified at the radiocapitellar
      joint. Minimal angular migration of the implant in the proximal radial shaft was
      observed over time. Complications included 1 patient requiring temporary
      placement of a hinged external fixator for instability and 1 patient requiring
      revision surgery at 4 weeks. CONCLUSION: This review demonstrates that a bipolar
      radial head prosthesis with a smooth stem and telescoping neck effectively
      restores stability to elbows with a comminuted radial head fracture and valgus
      instability. To date, this is the largest reported outcome analysis of bipolar
      radial head replacement in the literature.

PMID- 21856179
TI  - The taylor spatial frameTM for correction of neglected fracture dislocation of
      the ankle.
AB  - Treatment of neglected fracture dislocations of the ankle poses a surgical
      challenge. Extensive open reduction can frequently be contraindicated because of
      local skin conditions and contractures. The Taylor Spatial FrameTM (TSF) has been
      used to reduce and maintain reduction of complex fractures. Its use in fracture
      dislocation of the ankle joint has not been described. We describe a case where a
      TSF was used to reduce and treat a 6-week-old fracture dislocation of the ankle.
      The TSF is a versatile device, which has a role in the management of both acute
      and neglected fractures.

PMID- 21856180
TI  - Proximal phalangeal osteotomy with proximal interphalangeal joint arthrodesis for
      multiplanar deformities of the second toe: historical perspectives and review of
      a case series.
AB  - Combined transverse and sagittal plane deformities of the second toe represent a
      common painful condition encountered by the foot surgeon. After a period of
      conservative management, surgical intervention is often required. Historically, a
      number of surgical options have been described for the treatment of this
      condition, with the universal acknowledgment that an ideal surgical outcome is
      difficult to achieve and prone to failure. In this report, a review of previously
      described surgical techniques is presented, along with a retrospective analysis
      of 20 second toe surgical reconstructions, in 16 patients, performed between June
      2003 and October 2010. Subjective outcomes were assessed by means of a mailed
      questionnaire, and a subset (15 second toes in 11 patients) returned for follow
      up evaluation, including ascertainment of American Orthopaedic Foot & Ankle
      Society Clinical Rating System for Lesser Metatarsophalangeal-Interphalangeal
      Joint Surgery scores. Overall, the duration of follow-up was 38.25 +/- 25.82
      months, and the subset was followed up for 36.07 +/- 27.95 months. The
      preoperative visual analog pain score was 4.9 +/- 2.7, whereas the postoperative
      pain score was 1.6 +/- 2.47 (p < .001). The preoperative American Orthopaedic
      Foot & Ankle Society score was 44.57 +/- 17.76, whereas the postoperative score
      was 91.27 +/- 12.27 (p < .001). Based on the results of this investigation,
      pairing a basilar proximal phalangeal osteotomy with arthrodesis of the proximal
      interphalangeal joint, for correction of combined transverse and sagittal plane
      deformities, appears to yield satisfactory long-term results.

PMID- 21856181
TI  - Pushing the envelope beyond a centimeter in rectal cancer: oncologic implications
      of close, but negative margins.
AB  - BACKGROUND: The treatment of rectal cancer has improved significantly over the
      last century. Advances in surgical and adjuvant therapy coupled with a better
      understanding of the natural history have allowed for acceptance of progressively
      diminished margins for distal neoplasms. In order to better define oncologically
      safe distal margins, we performed a meta-analysis of the existing world's
      literature. STUDY DESIGN: Studies were identified on Medline and ISI Web of
      Science using key words rectal cancer and margin. Studies were excluded if
      specific margins and local recurrence rates could not be extracted. All analyses
      were performed using Comprehensive Meta-Analysis Software (Biostat). RESULTS:
      Twenty-one studies reported outcomes in relationship to distal margins. Seventeen
      studies, 4,885 patients, reported outcomes with margins of less than 1 cm.
      Analysis of all studies indicated a nonsignificant trend favoring greater
      margins. However, in order to understand distal margins in the context of current
      care standards, additional analyses were performed. Thirteen studies reported
      application of total mesorectal excision and/or radiation. There was no
      significant difference in local recurrence rates for margins less than 1 cm. In
      the 4 studies that reported neither total mesorectal excision nor radiation, a
      margin greater than 1 cm was favored. Increased recurrence rates and decreased
      survival were associated with positive final margins. CONCLUSIONS: When total
      mesorectal excision is combined with radiotherapy, excellent local control can be
      expected with sphincter preservation for distal rectal cancers when margins are
      less than 1 cm, as long as final pathologic margins are negative.

PMID- 21856182
TI  - Hepatic arterial infusion of doxorubicin-loaded microsphere for treatment of
      hepatocellular cancer: a multi-institutional registry.
AB  - BACKGROUND: Hepatic intra-arterial therapy for unresectable hepatocellular cancer
      (HCC) has been shown to improve overall survival, but can have significant
      toxicity. A recent prospective randomized controlled trial demonstrated superior
      response rates and significantly less morbidity and doxorubicin-related adverse
      events with drug-eluting beads with doxorubicin (DEBDOX) compared with
      conventional chemoembolization. The aim of this study was to confirm the efficacy
      of DEBDOX for the treatment of unresectable HCC. STUDY DESIGN: This open-label,
      multicenter, multinational single-arm study included 118 intermediate-staged HCC
      patients who were not candidates for transplantation or resection. Patients
      received DEBDOX at each treatment. Complications and response rates to treatment
      were analyzed. RESULTS: There were 118 patients who received a total of 186
      DEBDOX treatments with a median total treatment dose of 75 mg (range 38 to 150
      mg), and median overall total hepatic exposure of 150 mg (range 150 to 600 mg).
      Five lesions were targeted, with a median size of 5.3 cm (range 1.0 to 16.9 cm).
      Severe adverse events related to liver dysfunction were seen after 4% of
      treatments. Overall survival was a median of 14.2 months (range 5 to 30 months),
      with progression-free survival of 13 months and hepatic-specific progression-free
      survival of 16 months. Okuda class less than 1 at time of treatment, reduction of
      alpha-fetoprotein of 1,000 ng/mL at the first post-treatment evaluation, delivery
      of more than 200 mg doxorubicin, and less than 25% liver involvement were all
      predictors of favorable overall survival assessed by multivariable analyses.
      CONCLUSIONS: Hepatic intra-arterial injection of DEBDOX is safe and effective in
      the treatment of HCC, as demonstrated by a minimal complication rate and robust
      and durable tumor response.

PMID- 21856183
TI  - Appendectomy during pregnancy: follow-up of progeny.
AB  - BACKGROUND: The incidence of appendicitis in pregnant patients is 0.04% to 0.20%,
      making it the most common nonobstetric surgical procedure in pregnancy. This
      study examines whether an appendectomy during any stage of pregnancy affects
      future development of motor, sensory, and social skills of the progeny. STUDY
      DESIGN: A prospective survey was administered to women who underwent an
      appendectomy during pregnancy at Mount Sinai Hospital from 2000 to 2009. The
      survey, which ranged from 1 to 9 years postpartum, consisted of questions about
      motor, sensory, and social development of their progeny, based on established
      pediatric milestones. Data were collected from the medical records of mother and
      child. Additional follow-up was gathered from outpatient and emergency room
      records. RESULTS: Fifty-two pregnant patients underwent an appendectomy during
      our study period. All pregnancies continued to full term with the exception of
      one fetal death due to extreme prematurity. Twenty-nine patients completed the
      follow-up survey, making the yield response rate 55.8%. There were 7 (26.9%), 14
      (48.3%), and 8 (27.6%) appendectomies in the first, second, and third trimesters,
      respectively. Mean follow-up time was 47.2 months (range 13 to 117 months) after
      delivery. None of the children exhibited any developmental delay by their third
      year of life. Timing of the surgery (trimester) had no effect on child
      development. CONCLUSIONS: Appendectomy during pregnancy is not associated with
      developmental delays in children, regardless of which trimester the procedure was
      performed. All children in this study had normal motor, sensory, and social
      development by 3 years of age.

PMID- 21856184
TI  - Phyllodes tumors: race-related differences.
AB  - BACKGROUND: Phyllodes tumors (PT) are rare breast malignancies accounting for
      0.5% to 1% of all breast tumors. PT have unpredictable behavior, with recurrence
      rates as high as 40%. A dearth of information exists about racial differences;
      elucidation of these differences is the objective of this study. STUDY DESIGN: A
      retrospective review of patients treated for PT at either Moffitt Cancer Center
      or University of Texas Health Science Center San Antonio from 1999 to 2010.
      RESULTS: Of the 124 patients, 71 (57%) were treated at Moffitt Cancer Center and
      53 (42%) at University of Texas Health Science Center San Antonio. Mean age at
      diagnosis was 44 years (15 to 70 years). Thirty-three patients required
      mastectomy. Combining both cohorts, 42% of the patients were Caucasian, 43% were
      Hispanic, and 12% were black. Tumors were benign in 49% patients, borderline in
      35%, and malignant in 16%, with a higher percentage of borderline and malignant
      tumors in Hispanic patients (p < 0.01). Hispanic patients tended to have larger
      tumors and higher mitotic rates (p = 0.01; p = 0.03). At a median follow-up time
      of 13 months, the local recurrence rate (6.4%) was associated with tumor size,
      tumor grade, mitotic rate, and close margin status (<2 mm) (p <0.01; p = 0.01; p
      = 0.01; p = 0.04). However, these findings did not translate into a survival
      difference by race. CONCLUSIONS: In this multi-institutional review of PT we
      found substantial pathologic differences by race with higher-grade tumors present
      more often in Hispanic patients. These differences did not substantially affect
      outcomes at short-term follow-up. Further investigation into additional
      molecular, biologic factors, geographic impact, and socioeconomic factors is
      needed to more clearly delineate this finding.

PMID- 21856185
TI  - Patterns of surgical care and health disparities of treating pediatric finger
      amputation injuries in the United States.
AB  - BACKGROUND: Digital amputation in children is a very strong indication for
      replantation, but little is known about the epidemiology and distribution of care
      for pediatric finger amputation injuries in the United States. The specific aims
      of this study were to examine trends in the surgical management of pediatric
      finger amputation injuries in the United States from 2000 to 2006, and to
      identify potential treatment disparities among various demographic groups. STUDY
      DESIGN: Data from the 2000, 2003, and 2006 Healthcare Cost and Utilization
      Project Kids' Inpatient Database were used to identify discharge records
      containing at least one ICD-9-CM procedure code corresponding to digit amputation
      or replantation. National estimates were generated using weighted frequency
      calculations, and a weighted logistic regression model was used to examine the
      influence of various demographic factors on treatment. RESULTS: There were 1,321
      weighted discharge records that satisfied our inclusion criteria. From 2000 to
      2006, the rate of attempted digit replantation for pediatric finger amputation
      injuries has remained stable at approximately 40%. The majority of injuries were
      treated at nonchildren's (86%) and teaching (76%) hospitals; 52% of digit
      replantations were performed at hospitals with a volume of 1 to 2 digit
      replantations per year. We found that blacks (odds ratio [OR] 0.47), Hispanics
      (OR 0.37), and children without insurance (OR 0.38) were less likely to receive
      attempted replantation (all p < 0.05), even after controlling for potential
      confounding factors. CONCLUSIONS: The proportion of pediatric digit amputation
      injuries managed by replantation remained stable between 2000 and 2006. Whites
      and children with private health insurance were more likely to receive
      replantation than blacks, Hispanics, and children without health insurance, even
      after controlling for confounding factors.

PMID- 21856187
TI  - Endorectal T2-weighted MRI does not differentiate between favorable and adverse
      pathologic features in men with prostate cancer who would qualify for active
      surveillance.
AB  - OBJECTIVE: With the increased diagnosis of low grade, low volume, potentially non
      lethal disease, active surveillance (AS) has become an increasingly popular
      alternative for select men with low-risk prostate cancer. The absence of precise
      clinical staging modalities currently makes it difficult to predict which
      patients are most appropriate for AS. The goal of our study was to evaluate the
      ability of endorectal MRI (eMRI) to predict adverse pathologic features in
      patients who would otherwise qualify for an AS program. MATERIALS AND METHODS: We
      retrospectively reviewed our institution's radical prostatectomy (RP) database
      from 1991 to 2007 and identified 172 patients who would have qualified for AS and
      underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI
      findings were correlated to final pathology in order to assess the ability of
      staging eMRI to predict adverse pathologic features in patients suitable for AS.
      RESULTS: The mean age of our cohort was 59.8 +/- 6.2 years. The mean PSA at the
      time of diagnosis was 5.2 +/- 2.2 ng/ml. In 51% of patients, no discrete tumor
      was visualized on eMRI and in 49% of patients a discrete tumor was detected. At
      the time of RP, Gleason score upgrading, extracapsular extension, and a positive
      surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with
      documented tumor on eMRI did not have an increased incidence of adverse
      pathologic findings with regard to tumor volume (P = 0.31), extra-capsular
      extension (P = 0.82), Gleason upgrading (P = 0.92), seminal vesicle invasion (P =
      0.97), or positive surgical margin rate (P = 0.95) compared with those in whom no
      tumor was seen. CONCLUSION: Discrete tumor identification on eMRI is not
      predictive of adverse pathologic features in patients who would otherwise qualify
      for AS. eMRI likely does not provide additional information when prospectively
      evaluating patients for AS protocols.

PMID- 21856188
TI  - Comments regarding 'Agreement between computed tomography and ultrasound on
      abdominal aortic aneurysms and implications on clinical decisions'.

PMID- 21856186
TI  - Tight regulation of memory CD8(+) T cells limits their effectiveness during
      sustained high viral load.
AB  - To design successful vaccines for chronic diseases, an understanding of memory
      CD8(+) T cell responses to persistent antigen restimulation is critical. However,
      most studies comparing memory and naive cell responses have been performed only
      in rapidly cleared acute infections. Herein, by comparing the responses of memory
      and naive CD8(+) T cells to acute and chronic lymphocytic choriomeningitis virus
      infection, we show that memory cells dominated over naive cells and were
      protective when present in sufficient numbers to quickly reduce infection. In
      contrast, when infection was not rapidly reduced, because of high antigen load or
      persistence, memory cells were quickly lost, unlike naive cells. This loss of
      memory cells was due to a block in sustaining cell proliferation, selective
      regulation by the inhibitory receptor 2B4, and increased reliance on CD4(+) T
      cell help. Thus, emphasizing the importance of designing vaccines that elicit
      effective CD4(+) T cell help and rapidly control infection.

PMID- 21856189
TI  - Squamous cell carcinoma arising in a skin flap: case report and review on
      malignant transformations in skin grafts and microvascular cutaneous flaps.
AB  - OBJECTIVES: Sufficient closure of intraoral defects can be challenging. Various
      methods of tissue transfer have been presented in the literature. From skin
      grafts to microvascular flaps, most techniques used for intraoral reconstruction
      use skin to line out the oral cavity to guarantee an epithelial surface. Native
      mucosa tolerates the moist environment of the oral cavity, whereas skin flaps do
      to just a certain extent. This may lead to chronic inflammation of the flap-skin.
      Under rare circumstances, these histologic changes can enhance the risk for
      malignant transformation of the skin graft. CASE REPORT: We present a case of a
      patient who derived a squamous cell carcinoma in the skin island of a jump flap
      raised from the abdominal wall 30 years earlier. The flap was used to close a
      very wide palatal cleft. The patient had no history of malignancy, smoking,
      drinking, or other risk factors. DISCUSSION: To the authors' knowledge, this is
      the first report on carcinoma in a skin flap in a patient without any history of
      intraoral malignancy. Although malignant transformations of skin grafts are very
      rare and usually appear years after the reconstruction, one should be aware that
      the moist environment can lead to chronic inflammation of the dermis of flap.
      This fact may increase the risk of malignant transformation in a skin graft.

PMID- 21856190
TI  - The surgical management of a leiomyosarcoma of the submandibular gland in a 95
      year-old patient.
AB  - Primary sarcomas of the major salivary glands are rare and appear to originate
      from undifferentiated pluripotential mesenchymal cells. They must be
      distinguished from malignant supporting tissue neoplasms that secondarily involve
      the glands by direct extension or metastasis. Multidisciplinary management of
      head and neck soft tissue sarcomas is still controversial. We report a case of
      leiomyosarcoma of the submandibular gland in a 95-year-old man who was treated
      with excision of the right submandibular gland, extended to the surrounding
      tissues, without neck dissection. The patient tolerated the treatment well.
      Twenty-four months after surgery, the patient was doing well without any evidence
      of locoregional or distant disease. Surgery is the cornerstone of the management
      of leiomyosarcomas of the salivary glands. Wide surgical excision with
      histologically proven tumor-free margins was an appropriate treatment that may
      guarantee prolonged survival.

PMID- 21856192
TI  - Accelerated healing with the use of a silk fibroin membrane for the guided bone
      regeneration technique.
AB  - OBJECTIVE: The purpose of this study was to evaluate the bone regeneration
      ability of silk fibroin (SF) membrane. STUDY DESIGN: Fourier-transform infrared
      (FT-IR) and solubility test against distilled water were performed with 3
      different types of SF membrane (SM1, SM2, and SM3). Subsequently, microscopic
      computerized tomography (MU-CT) and histomorphometric analyses were performed in
      rabbit calvarial defect model after SF membrane application at 4 and 8 weeks
      after surgery. RESULTS: FT-IR showed that the conformation of the SF membrane was
      a random coil structure and that SM1 was the least soluble. When SM1 was used in
      the animal model, the groups with SM1 had significantly higher new bone formation
      than the uncovered control in both the MU-CT and the histomorphometric analyses
      (P < .05). CONCLUSIONS: The SF membrane had more new bone formation compared with
      the uncovered control.

PMID- 21856193
TI  - Effects of sodium hypochlorite on gutta-percha and Resilon cones: an atomic force
      microscopy and scanning electron microscopy study.
AB  - The aim of this study was to evaluate the effects of 6% sodium hypochlorite
      (NaOCl) on gutta-percha (GP) and Resilon cones. Six standardized GP and Resilon
      cones were selected and cut 3mm from their tip. One GP and 1 Resilon cone were
      used as control samples. Cones were immersed in 6% NaOCl for 1, 5, 10, 20, and 30
      minutes, thoroughly rinsed with nanopure water, and dried with filter paper.
      Then, surface topography was analyzed by atomic force microscopy and scanning
      electron microscopy coupled to an energy-dispersive x-ray (EDX) spectrometer.
      According to the root mean square and depth analysis values obtained from atomic
      force microscopic evalution, there were no significant differences found among
      the GP groups. However significant differences were found among Resilon cones (P
      <= .05). SEM images and EDX graphics showed that there were no prominent
      differences between GP and Resilon groups. These results showed that 6% NaOCl
      solution can be used in the disinfection of GP and Resilon cones. No alterations
      were observed on the GP cones, but it can change the surface of Resilon cones.

PMID- 21856195
TI  - Participatory epidemiology: approaches, methods, experiences.
AB  - Participatory epidemiology (PE) is an evolving branch of veterinary epidemiology
      which uses a combination of practitioner communication skills and participatory
      methods to improve the involvement of animal keepers in the analysis of animal
      disease problems, and the design, implementation and evaluation of disease
      control programmes and policies. This review describes the origins of PE and how
      the application of PE requires attention to both a participatory approach and
      participatory methods, supported by triangulation of data with conventional
      veterinary diagnostic methods. The review summarizes the various adaptations and
      uses of PE, including the design of primary veterinary service delivery systems,
      veterinary research and disease surveillance. In contrast to conventional data
      collection methods, an integral aspect PE is the concept of applying and
      evaluating new disease control programmes or surveillance systems in partnership
      with animal owners. In the developing regions where PE has been most commonly
      used, this action-orientated approach raises important challenges for veterinary
      institutions with limited financial resources. Information derived from PE
      studies can also question longstanding disease control policies and norms,
      nationally and internationally.

PMID- 21856197
TI  - Development of a temperature-variable magnetic resonance imaging system using a
      1.0T yokeless permanent magnet.
AB  - A temperature variable magnetic resonance imaging (MRI) system has been developed
      using a 1.0 T permanent magnet. A permanent magnet, gradient coils,
      radiofrequency coil, and shim coil were installed in a temperature variable
      thermostatic bath. First, the variation in the magnetic field inhomogeneity with
      temperature was measured. The inhomogeneity has a specific spatial symmetry,
      which scales linearly with temperature, and a single-channel shim coil was
      designed to compensate for the inhomogeneity. The inhomogeneity was drastically
      reduced by shimming over a wide range of temperature from -5 degrees C to 45
      degrees C. MR images of an okra pod acquired at different temperatures
      demonstrated the high potential of the system for visualizing thermally sensitive
      properties.

PMID- 21856200
TI  - Occurrence of occult bacteriuria in healthy cats.
AB  - Knowledge of the occurrence of bacteriuria in adult, healthy cats is scarce in
      the scientific literature. A study was designed to investigate the occurrence of
      bacteriuria in healthy cats without current or previous signs of lower urinary
      tract disease. The study included 108 cats, 53 males (49.5%) and 55 females
      (50.5%). The cats ranged in age between 7 months and 18 years, with a mean age of
      4.4 years and a median age of 4.0 years. Urine was obtained by cystocentesis from
      all the cats, and was submitted for bacteriological analyses. Urine and urine
      sediment was cultured on separate blood agar plates for quantification and
      species identification by standard procedures. Detection of >=10(3)colony forming
      units (cfu) per ml urine was defined as significant bacteriuria. Significant
      bacteriuria exceeding 10(5) cfu/ml was detected in one sample with a combination
      of Enterococcus species and Staphylococcus species. There was no bacterial growth
      in the urine samples from 107 cats (99.1%). Results from our study indicate that
      the prevalence of bacteriuria in clinically healthy, adult cats is low. Also,
      that contamination of samples is rare when urine is collected by cystocentesis.

PMID- 21856198
TI  - JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and
      blocks replication licensing in response to stress.
AB  - In response to environmental stresses, cells activate stress-response genes and
      inhibit DNA replication. HBO1 histone acetylase is a coactivator both for AP-1
      transcription factors responding to stress-activated JNK kinases and also for the
      Cdt1 licensing factor that ensures that DNA is replicated exactly once per cell
      cycle. In response to nongenotoxic stress, JNK phosphorylates Jun, an AP-1
      transcription factor, leading to increased recruitment of HBO1 and increased
      transcription of target genes. In addition, JNK phosphorylates Cdt1 on threonine
      29, leading to rapid dissociation of HBO1 from replication origins, thereby
      blocking initiation of DNA replication. Upon relief of stress, HBO1 reassociates
      with replication origins. Thus, regulated and reciprocal recruitment of the HBO1
      coactivator to target genes and replication origins via JNK-mediated
      phosphorylation of the recruiting transcription and replication licensing factors
      coordinates the transcriptional and DNA replication response to cellular stress.

PMID- 21856201
TI  - [Tendon entrapment after forearm distal bones fracture, case report].
AB  - In the aftermath of a forearm trauma, tendon contractures are difficult to
      diagnose and evoke nerve compression or muscle ischemia (Volkmann's syndrome).
      One rarely thinks of tendon incarceration within the fracture and the diagnosis
      is often made long after. During claw fingers retraction, it is known as "false
      Volkmann's syndrome" (Baudet and Lafond, 1979) or "pseudo Volkmann's syndrome"
      (Deeney et al., 1998). The authors report the case of ulnar claw fingers
      retraction, one year after a fracture of both bones of the forearm, treated
      surgically with recuperation of normal mobility immediately after emergence of
      the conflict.

PMID- 21856199
TI  - SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the
      development of the metabolic syndrome.
AB  - Acetylation is increasingly recognized as an important metabolic regulatory
      posttranslational protein modification, yet the metabolic consequence of
      mitochondrial protein hyperacetylation is unknown. We find that high-fat diet
      (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and
      downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking
      SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance,
      hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The
      lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and
      its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis
      and insulin resistance. We further identify a single nucleotide polymorphism in
      the human SIRT3 gene that is suggestive of a genetic association with the
      metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3
      protein, which reduces its overall enzymatic efficiency. Our findings show that
      loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute
      to the metabolic syndrome.

PMID- 21856202
TI  - [Rate of cervical intraepithelial neoplasia before HPV vaccination, Alpes
      Maritimes 2006].
AB  - OBJECTIVE: The incidence rate of uterix cervical cancer in 2006 in the Alpes
      Maritime was 6.2 per 100,000 women. The existence of curable precancerous lesions
      and an effective vaccine make it a target cancer in public health. The objective
      of this study was to establish prevalence of cervical intraepithelial neoplasia
      in 2006 before the campaign of vaccination against HPV. PATIENTS AND METHODS:
      Retrospective study including all histological samples (smears excluded) of the
      cervix, performed in 2006 with a diagnosis of intraepithelial Neoplasia among
      residents of the Alpes-Maritimes. Extraction codes' corresponding was carried out
      by all pathology laboratories located in the Alpes-Maritimes and around. A
      comparison of codes with pathology reports was performed for 11.4% of random
      samples. RESULTS: This study included 2066 patients aged 16 to 88 years. The
      average age was 37.3 years (+/-12.3). Among these patients, most pejorative
      intraepithelial neoplasia lesion was CIN 1, CIN 2, CIN 3, respectively for 941,
      380 and 375 patients. Prevalence of CIN 2 among women 20 to 25 years old was
      similar to rates seen in 35 to 39 years old (166.5 per 100,000) and the rate of
      CIN 3 was similar to that seen in 45 to 49 years (78.1 per 100,000). DISCUSSION
      AND CONCLUSION: Rates of CIN for the entire female population of the Alpes
      Maritimes in 2006 has been established. The results observed in women aged less
      than 25 years old will be useful for comparison after the campaign of vaccination
      against HPV.

PMID- 21856203
TI  - [Gynaecologists' attitudes and practices towards HPV vaccination: a quantitative
      qualitative study in Rhone-Alpes].
AB  - OBJECTIVES: Acceptance of the human papilloma virus (HPV) vaccine by targeted
      population will mainly depend on its acceptability among gynaecologists. We
      examined the perceptions, attitudes and practices of gynaecologists in relation
      to HPV vaccination 1 year after licensing. POPULATION AND METHODS: From November
      2007 to April 2008, a cross-sectional survey was carried among a representative
      10% sample of gynaecologists in the French Rhone-Alpes region. Both quantitative
      (self-administered questionnaire) and qualitative (interview) approaches were
      used. RESULTS: Among the 52 respondents, 90.4% of gynaecologists reported a
      favourable opinion about HPV vaccination, 5.8% were uncertain and 1.9% was
      opposed (one did not answer). The main justification for a favourable opinion
      related to the public health effects of the HPV vaccination (cited by 31.9% of
      those favouring vaccination). The main justification for an uncertain or opposed
      opinion was the too recent introduction of the vaccine (cited by 100%). During
      the month preceding the survey, 40.4% had provided HPV vaccination, mainly in 15
      23 years old girls (38.5%). The major difficulties in providing HPV vaccination
      were questions asked by patients (cited by 44.2% of the respondents) and the
      targeted age of 14 years (13.5%). A total of 87.5% of respondents reported to
      have discussed with 14-year-old vaccinated girls of Pap-smear and 12.5% of STI
      prevention. CONCLUSION: One year after HPV vaccine licensing, gynaecologists of
      Rhone-Alpes region had a favourable opinion about it, despite some difficulties.
      Little information about STI prevention to vaccinated girls was reported opposite
      to information about Pap-smear.

PMID- 21856204
TI  - Maximum Lyapunov exponents as predictors of global gait stability: a modelling
      approach.
AB  - To examine the stability of human walking, methods such as local dynamic
      stability have been adopted from dynamical systems theory. Local dynamic
      stability is calculated by estimating maximal finite time Lyapunov exponents
      (lambda(S) and lambda(L)), which quantify how a system responds continuously to
      very small (i.e. "local") perturbations. However, it is unknown if, and to what
      extent, these measures are correlated to global stability, defined operationally
      as the probability of falling. We studied whether changes in probability of
      falling of a simple model of human walking (a so-called dynamic walker) could be
      predicted from maximum finite time Lyapunov exponents. We used an extended
      version of the simplest walking model with arced feet and a hip spring. This
      allowed us to change the probability of falling of the model by changing either
      the foot radius, the slope at which the model walks, the stiffness of the hip
      spring, or a combination of these factors. Results showed that lambda(S)
      correlated fairly well with global stability, although this relationship was
      dependent upon differences in the distance between initial nearest neighbours on
      the divergence curve. A measure independent of such changes (the log(distance
      between initially nearest neighbours after 50 samples)) correlated better with
      global stability, and, more importantly, showed a more consistent relationship
      across conditions. In contrast, lambda(L) showed either weak correlations, or
      correlations opposite to expected, thus casting doubt on the use of this measure
      as a predictor of global gait stability. Our findings support the use of
      lambda(S), but not of lambda(L), as measure of human gait stability.

PMID- 21856205
TI  - Unilateral deep brain stimulation surgery in Parkinson's disease improves
      ipsilateral symptoms regardless of laterality.
AB  - PURPOSE: Researchers have consistently observed in right-handed individuals
      across normal and disease states that the 'dominant' left hemisphere has greater
      ipsilateral control of the left side than the right hemisphere has over the
      right. We sought to determine whether this ipsilateral influence of the dominant
      hemisphere reported in Parkinson's disease extends to treatments such as deep
      brain stimulation (DBS) and whether it affects outcome. We hypothesised that
      among Parkinson right-handers, unilateral left DBS would provide greater
      ipsilateral motor improvement compared with the ipsilateral motor improvement
      experienced on the right side. SCOPE: A total of 73 Parkinson patients who
      underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus
      internus (GPi) participated. Left and right 'composite scores', were computed by
      separately adding all items on the left and right side from the motor section of
      the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month
      post-implantation score was the primary outcome measure. The mean motor scores
      improved by 4.96 +/- 11.79 points (p < 0.001) post-surgery on the ipsilateral
      side of the DBS implantation. Regression analyses revealed that the side (left
      vs. right) and target (STN vs. GPi) did not significantly contribute in the
      effect of ipsilateral motor improvement (p = 0.3557). CONCLUSION: While DBS on
      the 'dominant' left side failed to exert a greater ipsilateral influence compared
      with DBS on the non-dominant right side, significant ipsilateral motor
      improvements were observed after unilateral stimulation regardless of site of
      implantation and laterality.

PMID- 21856208
TI  - Optimizing treatments of locally advanced squamous cell carcinoma: where to go
      from here?

PMID- 21856206
TI  - The relation between depression and parkin genotype: the CORE-PD study.
AB  - BACKGROUND: Mutations in parkin are a known genetic risk factor for early onset
      Parkinson's disease (EOPD) but their role in non-motor manifestations is not well
      established. Genetic factors for depression are similarly not well characterized.
      We investigate the role of parkin mutations in depression among those with EOPD
      and their relatives. METHODS: We collected psychiatric information using the
      Patient Health Questionnaire and Beck Depression Inventory II on 328 genotyped
      individuals including 88 probands with early onset PD (41 with parkin mutations,
      47 without) and 240 first and second-degree relatives without PD. RESULTS:
      Genotype was not associated with depression risk among probands. Among unaffected
      relatives of EOPD cases, only compound heterozygotes (n = 4), and not
      heterozygotes, had significantly increased risk of depressed mood (OR = 14.1; 95%
      CI 1.2-163.4), moderate to severe depression (OR = 17.8; 95% CI 1.0-332.0),
      depression (score >= 15) on the Beck Depression Inventory II (BDI-II) (OR = 51.9;
      95% CI 4.1-657.4), and BDI-II total depression score (beta = 8.4; 95% CI 2.4
      11.3) compared to those without parkin mutations. CONCLUSIONS: Relatives of EOPD
      cases with compound heterozygous mutations and without diagnosed PD may have a
      higher risk of depression compared to relatives without parkin mutations. These
      findings support evidence of a genetic contribution to depression and may extend
      the phenotypic spectrum of parkin mutations to include non-motor manifestations
      that precede the development of PD.

PMID- 21856209
TI  - Head and neck specific Health Related Quality of Life scores predict subsequent
      survival in successfully treated head and neck cancer patients: a prospective
      cohort study.
AB  - To examine the survival prediction of head and neck (H&N) Health Related Quality
      of Life (HRQoL) scores among successfully treated and cognitive functioning H&N
      squamous cell carcinoma (HNSCC) patients. Through structured interviews, self
      reported questionnaires were given to 139 successfully treated HNSCC patients, 67
      +/- 32 months following diagnosis. HRQoL-scores, measured with the EORTC QLQ
      H&N35 inventory, self-reported levels of neuroticism, avoidance focused coping,
      coping by suppression of competing activity, alcohol consumption, smoking status,
      and heart and lung disease, as well as gender, age, TNM-stage, and tumor site
      were determined. The mean observation period was 75 +/- 4 months among the
      survivors. Twenty-four deaths were observed. A EORTC QLQ-H&N 35 sum score,
      including a dichotomized version (HR 2.73-3.67), was predictive of survival, both
      directly and after adjustment for all of the above mentioned variables. The H&N
      HRQoL indices "feeling ill", "sexuality", "open mouth", "swallowing", and "pain"
      specifically predicted survival. The dichotomized H&N HRQoL sum score compared
      the 4th upper quartile to the three lower quartiles, and a cut off value of 28.5
      was designated. Analyses demonstrated that a high risk group with 33% mortality
      may include only one quarter of the patient population as opposed to 12.5%
      mortality among the other patients. Our findings indicate a unique survival
      prediction from EORTC QLQ-H&N 35 sum scores in successfully treated HNSCC
      patients. HRQoL scores, in particular, related to oral health, predicted
      survival. Furthermore, HRQoL-scores may be a screening tool for identifying
      patients with high mortality risk.

PMID- 21856207
TI  - Replication initiation at the Escherichia coli chromosomal origin.
AB  - To initiate DNA replication, DnaA recognizes and binds to specific sequences
      within the Escherichia coli chromosomal origin (oriC), and then unwinds a region
      within oriC. Next, DnaA interacts with DnaB helicase in loading the DnaB-DnaC
      complex on each separated strand. Primer formation by primase (DnaG) induces the
      dissociation of DnaC from DnaB, which involves the hydrolysis of ATP bound to
      DnaC. Recent evidence indicates that DnaC acts as a checkpoint in the transition
      from initiation to the elongation stage of DNA replication. Freed from DnaC, DnaB
      helicase unwinds the parental duplex DNA while interacting the cellular
      replicase, DNA polymerase III holoenzyme, and primase as it intermittently forms
      primers that are extended by the replicase in duplicating the chromosome.

PMID- 21856210
TI  - Apicidin, a histone deaceylase inhibitor, induces both apoptosis and autophagy in
      human oral squamous carcinoma cells.
AB  - Apicidin acts as a potent histone deacetylases (HDAC) inhibitor and the precise
      mechanism for its anti-tumor activity in human oral squamous cell carcinoma
      (OSCC) cells has not been examined. The aim of this study was to evaluate the
      anti-tumor efficacy of apicidin through apoptosis and autophagy in OSCC cells.
      Cells were treated with apicidin and cell death was quantified. Cell cycle and
      apoptosis were measured using flow cytometry assay, immunoblot. Autophagy was
      characterized by the increase of LC3B-II and the formation of acidic vesicular
      organelles (AVOs). Apicidin significantly inhibited the proliferation of OSCC
      cells in a dose-dependent manner. Apicidin markedly up-regulated p21(WAF1) led to
      G2/M phase arrest. Apicidin significantly increased the number of apoptotic cells
      compared to untreated control. Apicidin induced not only apoptosis but also
      autophagy in OSCC cells. Apicidin dramatically increased the levels of LC3 type
      II expression, ATG5 protein expression and the accumulation of AVOs. Inhibition
      of autophagy enhanced apicidin-mediated cytotoxicity through an increase in
      apoptosis. These results suggest that apicidin exerts anti-tumor effects by
      inducing apoptosis and autophagy and provide novel evidence of apicidin-induced
      autophagy and autophagy inhibition enhances apicidin-mediated apoptosis in OSCC
      cells.

PMID- 21856211
TI  - Diagnostic value of magnetic resonance lymphography in preoperative staging of
      clinically negative necks in squamous cell carcinoma of the oral cavity: a pilot
      study.
AB  - Pilot study evaluating the diagnostic value of magnetic resonance lymphography
      (MRL) compared with conventional imaging techniques in the preoperative staging
      of the clinically (palpable) negative neck (cN0) in squamous cell carcinoma of
      the oral cavity (SCCOC). Patients with SCCOC without clinical evidence of lymph
      node metastasis and scheduled for surgery underwent MRL in combination with
      ultrasound with or without fine needle aspiration cytology and multi-detector
      computer tomography. MRL images were interpreted by 2 independent radiologists.
      All patients were planned for resection of the primary tumor and a selective neck
      dissection of levels I-III. Histopathologic results were evaluated as the gold
      standard and compared with preoperative findings. One of nine evaluated patients
      had a metastatic node on histopathologic analysis. In all but 1 patient, MRL
      showed possible metastatic spread in at least 1 node. On a node-to-node basis,
      negative predictive value (NPV) and sensitivity reached 100% for 1.5- en 3Tesla
      (T) MRL, specificity reached 92% at 1.5T and 93% at 3T MRL, and positive
      predictive value (PPV) was 8% at 1.5T MRL, for both radiologists. PPV at 3T MRL
      was 10% and 9%, for radiologists I and II, respectively. This pilot study shows
      that MRL has a high NPV based on a node-to-node analysis. However, its PPV was
      only 10%, and therefore its use as a single imaging technique in the preoperative
      staging of the cN0 neck in SCCOC seems to be limited. Further studies are needed
      to confirm these data.

PMID- 21856212
TI  - The impact of enteral feeding route on patient-reported long term swallowing
      outcome after chemoradiation for head and neck cancer.
AB  - Prospective evidence suggests that the selection of feeding tube during
      chemoradiation (CRT) indirectly affects swallowing outcome. This study explores
      the patients' perspective on long-term swallowing ability comparing these two
      feeding routes. Two groups, receiving nutritional supplementation via a
      prophylactic gastrostomy tube (group G) and by the oral route or via a
      nasogastric tube (group NG) during CRT, disease-free at >=24 months following
      treatment were matched for age, site and stage of tumour. Patient-reported
      swallowing outcomes for both groups were assessed using the MD Anderson Dysphagia
      Inventory (MDADI). Group G consisted of 16 patients and group NG of 15 patients.
      There was statistically significant difference in MDADI scores between the two
      groups in all domains of the questionnaire (p<0.001), with superior outcomes in
      group NG. Use of gastrostomy tubes during CRT conferred a worse swallowing
      outcome in the long term in this tightly matched cohort of patients.

PMID- 21856213
TI  - Trends and barriers to lateral gene transfer in prokaryotes.
AB  - Gene acquisition by lateral gene transfer (LGT) is an important mechanism for
      natural variation among prokaryotes. Laboratory experiments show that protein
      coding genes can be laterally transferred extremely fast among microbial cells,
      inherited to most of their descendants, and adapt to a new regulatory regime
      within a short time. Recent advance in the phylogenetic analysis of microbial
      genomes using networks approach reveals a substantial impact of LGT during
      microbial genome evolution. Phylogenomic networks of LGT among prokaryotes
      reconstructed from completely sequenced genomes uncover barriers to LGT in
      multiple levels. Here we discuss the kinds of barriers to gene acquisition in
      nature including physical barriers for gene transfer between cells, genomic
      barriers for the integration of acquired DNA, and functional barriers for the
      acquisition of new genes.

PMID- 21856214
TI  - A spectroscopic study of phenylbutazone and aspirin bound to serum albumin in
      rheumatoid diseases.
AB  - Interaction of phenylbutazone (PBZ) and aspirin (ASA), two drugs recommended in
      rheumatoid diseases (RDs), when binding to human (HSA) and bovine (BSA) serum
      albumins, has been studied by quenching of fluorescence and proton nuclear
      magnetic resonance ((1)HNMR) techniques. On the basis of spectrofluorescence
      measurements high affinity binding sites of PBZ and ASA on albumin as well as
      their interaction within the binding sites were described. A low affinity binding
      site has been studied by proton nuclear magnetic resonance spectroscopy. Using
      fluorescence spectroscopy the location of binding site in serum albumin (SA) for
      PBZ and ASA was found. Association constants K(a) were determined for binary
      (i.e. PBZ-SA and ASA-SA) and ternary complexes (i.e. PBZ-[ASA]-SA and ASA-[PBZ]
      SA). PBZ and ASA change the affinity of each other to the binding site in serum
      albumin (SA). The presence of ASA causes the increase of association constants
      K(aI) of PBZ-SA complex. Similarly, PBZ influences K(aI) of ASA-SA complex. This
      phenomenon shows that the strength of binding and the stability of the complexes
      increase in the presence of the second drug. The decrease of K(aII) values
      suggests that the competition between PBZ and ASA in binding to serum albumin in
      the second class of binding sites occurs. The analysis of (1)HNMR spectral
      parameters i.e. changes of chemical shifts and relaxation times of the drug
      indicate that the presence of ASA weakens the interaction of PBZ with albumin.
      Similarly PBZ weakens the interaction of ASA with albumin. This conclusion points
      to the necessity of using a monitoring therapy owning to the possible increase of
      uncontrolled toxic effects.

PMID- 21856215
TI  - Synthesis, structural characterization and antimicrobial activity evaluation of
      metal complexes of sparfloxacin.
AB  - The synthesis and characterization of binary Cu(II)- (1), Co(II)- (2), Ni(II)-
      (3), Mn(II)- (4), Cr(III)- (5), Fe(III)- (6), La(III)- (7), UO(2)(VI)- (8)
      complexes with sparfloxacin (HL(1)) and ternary Cu(II)- (9), Co(II)- (10), Ni(II)
      (11), Mn(II)- (12), Cr(III)- (13), Fe(III)- (14), La(III)- (15), UO(2)(VI)- (16)
      complexes with sparfloxacin (HL(1)) and DL-alanine (H(2)L(2)) complexes are
      reported using elemental analysis, molar conductance, magnetic susceptibility,
      IR, UV-Vis, thermal analysis and (1)H-NMR spectral studies. The molar conductance
      measurements of all the complexes in DMF solution correspond to non-electrolytic
      nature. All complexes were of the high-spin type and found to have six-coordinate
      octahedral geometry except the Cu(II) complexes which were four coordinate,
      square planar and U- and La-atoms in the uranyl and lanthanide have a pentagonal
      bipyramidal coordination sphere. The antimicrobial activity of these complexes
      has been screened against two gram-positive and two gram-negative bacteria.
      Antifungal activity against two different fungi has been evaluated and compared
      with reference drug sparfloxacin. All the binary and ternary complexes showed
      remarkable potential antimicrobial activity higher than the recommended standard
      agents. Ni(II)- and Mn(II) complexes exhibited higher potency as compared to the
      parent drug against gram-negative bacteria.

PMID- 21856216
TI  - Molecular structure, vibrational spectra and HOMO, LUMO analysis of yohimbine
      hydrochloride by density functional theory and ab initio Hartree-Fock
      calculations.
AB  - Yohimbine hydrochloride (YHCl) is an aphrodisiac and promoted for erectile
      dysfunction, weight loss and depression. The optimized geometry, total energy,
      potential energy surface and vibrational wavenumbers of yohimbine hydrochloride
      have been determined using ab initio, Hartree-Fock (HF) and density functional
      theory (DFT/B3LYP) method with 6-311++G(d,p) basis set. A complete vibrational
      assignment is provided for the observed Raman and IR spectra of YHCl. The UV
      absorption spectrum was examined in ethanol solvent and compared with the
      calculated one in gas phase as well as in solvent environment (polarizable
      continuum model, PCM) using TD-DFT/6-31G basis set. These methods are proposed as
      a tool to be applied in the structural characterization of YHCl. The calculated
      highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital
      (LUMO) with frontier orbital gap are presented.

PMID- 21856217
TI  - Spectroscopic analysis on the resveratrol-DNA binding interactions at
      physiological pH.
AB  - The interaction of resveratrol with calf thymus deoxyribonucleic acid (ctDNA)
      under physiological conditions (Tris-HCl buffer solutions, pH 7.4) was studied by
      spectroscopy, fluorescence spectroscopy and viscosity measurement method,
      respectively. Results indicated that a complex of resveratrol with ctDNA was
      formed with a binding constant of K(17 degrees C) = 5.49*10(3) L mol(-1) and K(37
      degrees C) = 1.90*10(4) L mol(-1). The fluorescence quenching mechanism of
      acridine orange (AO)-ctDNA by resveratrol was shown to be a static quenching
      type. The thermodynamic parameters of the complex were calculated by a double
      reciprocal method: Delta(r)H(m)(s) = 4.64*10(4)  J  mol(-1), Delta(r)S(m)(s) =
      231.8  J  K(-1)  mol(-1) and Delta(r)G(m)(s) = -2.54*10(4)  J  mol(-1) (37
      degrees C). Spectroscopic techniques together with viscosity determination
      provided evidences of intercalation mode of binding for the interaction between
      resveratrol and ctDNA.

PMID- 21856218
TI  - Synthesis, molecular conformation, vibrational and electronic transition,
      isometric chemical shift, polarizability and hyperpolarizability analysis of 3-(4
      methoxy-phenyl)-2-(4-nitro-phenyl)-acrylonitrile: a combined experimental and
      theoretical analysis.
AB  - This work presents the synthesis and characterization of a novel compound, 3-(4
      methoxy-phenyl)-2-(4-nitro-phenyl)-acrylonitrile (abbreviated as 3-(4MP)-2-(4-NP)
      AN, C(16)H(12)N(2)O(3)). The spectroscopic properties of the compound were
      examined by FT-IR, UV-vis and NMR ((1)H and (13)C) techniques. FT-IR spectrum in
      solid state was observed in the region 4000-400 cm(-1). The UV-vis absorption
      spectrum of the compound which dissolved in chloroform was recorded in the range
      of 200-800 nm. The (1)H and (13)C NMR spectra were recorded in CDCl(3) solution.
      To determine lowest-energy molecular conformation of the title molecule, the
      selected torsion angle is varied every 10 degrees  and molecular energy profile
      is calculated from 0 degrees  to 360 degrees . The structural and spectroscopic
      data of the molecule in the ground state were calculated using density functional
      theory (DFT) employing B3LYP/6-31G(d,p) basis set. The dipole moment, linear
      polarizability and first hyperpolarizability values were also computed using the
      same basis set. A study on the electronic properties, such as HOMO and LUMO
      energies, were performed by time-dependent DFT (TD-DFT) approach. The HOMO and
      LUMO analysis were used to elucidate information regarding charge transfer within
      the molecule. The vibrational wavenumbers were calculated and scaled values were
      compared with experimental FT-IR spectrum. The complete assignments were
      performed on the basis of the experimental results and total energy distribution
      (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM)
      method. Isotropic chemical shifts were calculated using the gauge-invariant
      atomic orbital (GIAO) method. Comparison of the calculated frequencies, NMR
      chemical shifts, absorption wavelengths with the experimental values revealed
      that DFT and TD-DFT method produce good results. The linear polarizabilities and
      first hyperpolarizabilities of the studied molecule indicate that the title
      compound can be used as a good nonlinear optical material. The thermodynamic
      properties of the studied compound at different temperatures were calculated,
      revealing the correlations between standard heat capacity, standard entropy,
      standard enthalpy changes and temperatures.

PMID- 21856219
TI  - Vibrational spectroscopic analysis of the mineral crandallite
      CaAl3(PO4)2(OH)5.(H2O) from the Jenolan Caves, Australia.
AB  - The mineral crandallite CaAl(3)(PO(4))(2)(OH)(5).(H(2)O) has been identified in
      deposits found in the Jenolan Caves, New South Wales, Australia by using a
      combination of X-ray diffraction and Raman spectroscopic techniques. A comparison
      is made between the vibrational spectra of crandallite found in the Jenolan Caves
      and a standard crandallite. Raman and infrared bands are assigned to PO(4)(3-)
      and HPO(4)(2-) stretching and bending modes. The predominant features are the
      internal vibrations of the PO(4)(3-) and HPO(4)(2-) groups. A mechanism for the
      formation of crandallite is presented and the conditions for the formation are
      elucidated.

PMID- 21856220
TI  - The structure of the mineral leogangite Cu10(OH)6(SO4)(AsO4)4.8H2O--implications
      for arsenic accumulation and removal.
AB  - The objective of this research is to determine the molecular structure of the
      mineral leogangite. The formation of the types of arsenosulphate minerals offers
      a mechanism for arsenate removal from soils and mine dumps. Raman and infrared
      spectroscopy have been used to characterise the mineral. Observed bands are
      assigned to the stretching and bending vibrations of (SO(4))(2-) and (AsO(4))(3-)
      units, stretching and bending vibrations of hydrogen bonded (OH)(-) ions and
      Cu(2+)-(O,OH) units. The approximate range of O-H?O hydrogen bond lengths is
      inferred from the Raman spectra. Raman spectra of leogangite from different
      origins differ in that some spectra are more complex, where bands are sharp and
      the degenerate bands of (SO(4))(2-) and (AsO(4))(3-) are split and more intense.
      Lower wavenumbers of delta H(2)O bending vibration in the spectrum may indicate
      the presence of weaker hydrogen bonds compared with those in different leogangite
      samples. The formation of leogangite offers a mechanism for the removal of
      arsenic from the environment.

PMID- 21856221
TI  - Synthesis, spectroscopy, and thermal study of uranyl unsymmetrical Schiff base
      complexes.
AB  - The new uranyl complexes with tetradentate unsymmetrical N(2)O(2) Schiff base
      ligands were synthesized and characterized by IR, UV-vis, NMR and elemental
      analysis. The DMF solvent is coordinated to uranyl complexes. The
      thermogravimetry (TG) and differential thermoanalysis (DTA) of the uranyl
      complexes were carried out in the range of 20-700 degrees C. The UO(2)L(1)
      complex was decomposed in two and the others were decomposed in three stages. Up
      to 100 degrees C, the coordinated solvent was released then the Schiff base
      ligands were decomposed in one or two steps. Decomposition of synthesized
      complexes is related to the Schiff base characteristics. The thermal
      decomposition reaction is first order for the studied complexes.

PMID- 21856222
TI  - Production of first generation adenoviral vectors for preclinical protocols:
      amplification, purification and functional titration.
AB  - Gene therapy represents a promising approach in the treatment of several
      diseases. Currently, the ideal vector has yet to be designed; though, adenoviral
      vectors (Ad-v) have provided the most utilized tool for gene transfer due
      principally to their simple production, among other specific characteristics. Ad
      v viability represents a critical variable that may be affected by storage or
      shipping conditions and therefore it is advisable to be assessed previously to
      protocol performance. The present work is unique in this matter, as the complete
      detailed process to obtain Ad-v of preclinical grade is explained. Amplification
      in permissive HEK-293 cells, purification in CsCl gradients in a period of 10 h,
      spectrophotometric titration of viral particles (VP) and titration of infectious
      units (IU), yielding batches of AdbetaGal, AdGFP, AdHuPA and AdMMP8, of
      approximately 1013-1014 VP and 1012-1013 IU were carried out. In vivo
      functionality of therapeutic AdHuPA and AdMMP8 was evidenced in rats presenting
      CCl4-induced fibrosis, as more than 60% of fibrosis was eliminated in livers
      after systemic delivery through iliac vein in comparison with irrelevant
      AdbetaGal. Time required to accomplish the whole Ad-v production steps, including
      IU titration was 20 to 30 days. We conclude that production of Ad-v following
      standard operating procedures assuring vector functionality and the possibility
      to effectively evaluate experimental gene therapy results, leaving aside the use
      of high-cost commercial kits or sophisticated instrumentation, can be performed
      in a conventional laboratory of cell culture.

PMID- 21856223
TI  - The 184th residue of beta-glucosidase Bgl1B plays an important role in glucose
      tolerance.
AB  - Bgl1B (ACY09072) is a new GH1 family beta-glucosidase derived from a marine
      microbial metagenomic library. In our previous study, the activity of recombinant
      Bgl1B was competitively inhibited by glucose with an IC50 value of 30 mM. Based
      on amino acids sequence alignment with other GH1 beta-glucosidases, including
      BglB from Paenibacillus polymyxa whose structure has been solved, the 184th and
      409th residues of Bgl1B were suggested to be key residues relating to glucose
      tolerance or other properties. The putative role of the two residues of Bgl1B was
      investigated by site-directed mutagenesis by replacing His184 and Leu409 with Phe
      and Glu, respectively. Biochemical characterization data indicated that the
      mutations had little influence on the enzyme properties. However, in comparison
      with wild-type Bgl1B, the mutant H184F exhibited lower stability at all tested
      temperatures and pHs, while L409E exhibited higher stability. Particularly, when
      using 4-Nitrophenyl-beta-D-glucopyranoside (pNPG) as substrate, the mutant H184F
      exhibited much better glucose tolerance, with a K(i) of 76.9 mM, than L409E and
      wild-type Bgl1B (17.2 mM and 14.9 mM, respectively). These results indicated that
      the 184th residue might play an important role in the glucose tolerance of Bgl1B.

PMID- 21856224
TI  - Measurement of subacromial impingement of the rotator cuff.
AB  - OBJECTIVE: Recent evidence suggests that shoulder impingement syndrome arises
      from primary rotator cuff pathology and may be related to the inability of the
      rotator cuff to prevent superior humeral head migration in shoulder elevation.
      Impingement involves compression of subacromial structures, including the rotator
      cuff. Previously, clinical tests have been shown to be inaccurate in diagnosing
      rotator cuff impingement. A lack of anatomical validity might explain the
      inaccuracy of these tests. This study aimed to clarify the anatomical basis of
      subacromial compression of the rotator cuff by analysing the compression forces
      generated and observing the structures impinged in a variety of shoulder
      positions. DESIGN: This observational case series involved the dissection of nine
      embalmed cadaveric shoulders. METHOD: Pressure transducers were placed deep to
      the coracoid process, coracoacromial ligament, the anterior acromion and the
      posterior acromion. Shoulders were moved into internal and external rotation from
      the positions of flexion, abduction and extension. At each position, pressure
      readings were recorded and structures being compressed observed visually.
      RESULTS: Highest pressures were recorded in flexion/internal rotation at the
      coracoacromial ligament, in abduction/internal rotation at the coracoid process
      (both involving the rotator interval) and in abduction/internal rotation at the
      coracoacromial ligament (involving supraspinatus). Supraspinatus was also
      observed to be compressed in extension/external rotation (against the anterior
      acromion). Infraspinatus was compressed in extension/external rotation (against
      the posterior acromion), while subscapularis was compressed in flexion/internal
      rotation and flexion/external rotation (both against the coracoid process).
      CONCLUSION: This study identifies shoulder positions likely to impinge particular
      rotator cuff tendons.

PMID- 21856225
TI  - Left-ventricular non-compaction with congenital left ventricular diverticulum.
AB  - Left-ventricular non-compaction may be isolated or associated with other cardiac
      or noncardiac anomalies. Left-ventricular non-compaction associated with left
      ventricular diverticulum is very rare. We describe a 30 year-old pregnant woman
      with a long standing diagnosis of biventricular non-compaction in whom a hidden
      left ventricular apical diverticulum was detected on transthoracic
      echocardiography. Both these conditions increase the risk of thromboembolism.
      Additionally, she was also diagnosed to have endocervical adenocarcinoma. This
      case suggests that a comprehensive echocardiographic examination is mandatory in
      cases of suspected isolated left-ventricular non-compaction to detect any other
      associated cardiac or noncardiac anomalies.

PMID- 21856226
TI  - Nilotinib versus imatinib for the treatment of patients with newly diagnosed
      chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24
      month minimum follow-up of the phase 3 randomised ENESTnd trial.
AB  - BACKGROUND: Nilotinib has shown greater efficacy than imatinib in patients with
      newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML)
      in chronic phase after a minimum follow-up of 12 months. We present data from the
      Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed
      patients (ENESTnd) study after a minimum follow-up of 24 months. METHODS: ENESTnd
      was a phase 3, multicentre, open-label, randomised study. Adult patients were
      eligible if they had been diagnosed with chronic phase, Philadelphia chromosome
      positive CML within the previous 6 months. Patients were randomly assigned
      (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or
      imatinib 400 mg once a day, all administered orally, by use of a computer
      generated randomisation schedule, using permuted blocks, and stratified according
      to Sokal score. Efficacy results are reported for the intention-to-treat
      population. The primary endpoint was major molecular response at 12 months,
      defined as BCR-ABL transcript levels on the International Scale (BCR-ABL(IS)) of
      0.1% or less by real-time quantitative PCR in peripheral blood. This study is
      registered with ClinicalTrials.gov, number NCT00471497. FINDINGS: 282 patients
      were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive
      nilotinib 400 mg twice daily, and 283 to receive imatinib. By 24 months,
      significantly more patients had a major molecular response with nilotinib than
      with imatinib (201 [71%] with nilotinib 300 mg twice daily, 187 [67%] with
      nilotinib 400 mg twice daily, and 124 [44%] with imatinib; p<0.0001 for both
      comparisons). Significantly more patients in the nilotinib groups achieved a
      complete molecular response (defined as a reduction of BCR-ABL(IS) levels to
      <=0.0032%) at any time than did those in the imatinib group (74 [26%] with
      nilotinib 300 mg twice daily, 59 [21%] with nilotinib 400 mg twice daily, and 29
      [10%] with imatinib; p<0.0001 for nilotinib 300 mg twice daily vs imatinib,
      p=0.0004 for nilotinib 400 mg twice daily vs imatinib). There were fewer
      progressions to accelerated or blast phase on treatment, including clonal
      evolution, in the nilotinib groups than in the imatinib group (two with nilotinib
      300 mg twice daily, five with nilotinib 400 mg twice daily, and 17 with imatinib;
      p=0.0003 for nilotinib 300 mg twice daily vs imatinib, p=0.0089 for nilotinib 400
      mg twice daily vs imatinib). At 24 months, survival was comparable in all
      treatment groups, but fewer CML-related deaths had occurred in both the nilotinib
      groups than in the imatinib group (five with nilotinib 300 mg twice daily, three
      with nilotinib 400 mg twice daily, and ten with imatinib). Overall, the only
      grade 3 or 4 non-haematological adverse events that occurred in at least 2.5% of
      patients were headache (eight [3%] with nilotinib 300 mg twice daily, four [1%]
      with nilotinib 400 mg twice daily, and two [<1%] with imatinib) and rash (two
      [<1%], seven [3%], and five [2%], respectively). Grade 3 or 4 neutropenia was
      more common with imatinib than with either dose of nilotinib (33 [12%] with
      nilotinib 300 mg twice daily, 30 [11%] with nilotinib 400 mg twice daily, and 59
      [21%] with imatinib). Serious adverse events were reported in eight additional
      patients in the second year of the study (four with nilotinib 300 mg twice daily,
      three with nilotinib 400 mg twice daily, and one with imatinib). INTERPRETATION:
      Nilotinib continues to show better efficacy than imatinib for the treatment of
      patients with newly diagnosed CML in chronic phase. These results support
      nilotinib as a first-line treatment option for patients with newly diagnosed
      disease. FUNDING: Novartis.

PMID- 21856227
TI  - First-line therapy for CML: nilotinib comes of age.

PMID- 21856228
TI  - Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort
      study of 487 infertile couples.
AB  - This study investigated the impact of women's body mass index (BMI) on the
      outcome after consecutive IVF/intracytoplasmic sperm injection cycles in 487
      patients initiating treatment with 5-year follow-up. The total number of cycles
      was 1417. In total 103 (21.1%) were overweight (BMI 25-29.9 kg/m2) and 59 (12.1%)
      were obese (BMI >= 30 kg/m2). Number of initiated cycles/woman (P=0.01), number
      of cancelled cycles/woman (P < 0.01) and the total dose of gonadotrophin
      used/cycle (P < 0.01) rose with increasing BMI. A negative linear association
      between BMI and the number of retrieved oocytes (B=-0.243, P < 0.001) and an
      inverse U-shaped relationship between BMI and the number of developed embryos was
      seen, with less embryos available among underweight and obese women (P=0.03). The
      number with positive serum human chorionic gonadotrophin/cycle decreased
      significantly with increasing BMI (P < 0.01). The ongoing pregnancy rate/cycle
      among the obese women was lower (20.8% versus 28.3% in normal-weight women;
      P=0.04). Live-birth rate per cycle was 15.2% versus 21.5%. Multiple logistic
      regression analysis showed that the only independent predictors of live birth
      were women's age (P=0.037), women's BMI (P=0.034) and men's age (P=0.040).

PMID- 21856229
TI  - PGD and aneuploidy screening for 24 chromosomes: advantages and disadvantages of
      competing platforms.
AB  - Diagnosis of embryos for chromosome abnormalities, i.e. aneuploidy screening, has
      been invigorated by the introduction of microarray-based testing methods allowing
      analysis of 24 chromosomes in one test. Recent data have been suggestive of
      increased implantation and pregnancy rates following microarray testing.
      Preimplantation genetic diagnosis for infertility aims to test for gross
      chromosome changes with the hope that identification and transfer of normal
      embryos will improve IVF outcomes. Testing by some methods, specifically single
      nucleotide polymorphism (SNP) microarrays, allow for more information and
      potential insight into parental origin of aneuploidy and uniparental disomy. The
      usefulness and validity of reporting this information is flawed. Numerous papers
      have shown that the majority of meiotic errors occur in the egg, while mitotic
      errors in the embryo affect parental chromosomes at random. Potential mistakes
      made in assigning an error as meiotic or mitotic may lead to erroneous reporting
      of results with medical consequences. This study's data suggest that the
      bioinformatic cleaning used to 'fix' the miscalls that plague single-cell whole
      genome amplification provides little improvement in the quality of useful data.
      Based on the information available, SNP-based aneuploidy screening suffers from a
      number of serious issues that must be resolved.

PMID- 21856230
TI  - No association between endogenous LH and pregnancy in a GnRH antagonist protocol:
      part I, corifollitropin alfa.
AB  - The relationship between endogenous LH concentrations and ongoing pregnancy rates
      among normogonadotrophic patients undergoing ovarian stimulation in a
      gonadotrophin-releasing hormone antagonist protocol were examined. In the Engage
      trial, 1506 patients received corifollitropin alfa (150 MUg) or daily recombinant
      FSH (rFSH) (200 IU) for the first 7 days of stimulation with 0.25mg ganirelix
      from stimulation day 5. Patients were retrospectively stratified by serum LH
      percentiles (< 25th, 25th-75th and >75th) on stimulation day 8 and day of human
      chorionic gonadotrophin administration. Odds ratios (OR) with and without
      adjustment for predictive factors for ongoing pregnancy were estimated. LH
      concentration was not associated with pregnancy rates in either treatment arm, in
      contrast to ovarian response and serum progesterone. With adjustment for these
      predictors and age, OR (95% confidence interval) for ongoing pregnancy on
      stimulation day 8 for LH categories < P25 versus >= P25, >P75 versus <= P75 and <
      P25 versus >P75 were 0.75 (0.53-1.06), 1.26 (0.87-1.83) and 0.70 (0.46-1.09) in
      the corifollitropin alfa arm and 0.80 (0.54-1.17), 1.28 (0.87-1.87) and 0.73
      (0.46-1.16) in the rFSH arm respectively. There was also no significant
      difference in pregnancy rates between LH categories on day of human chorionic
      gonadotrophin administration with either treatment.

PMID- 21856231
TI  - Alloimmunization to red cells in thalassemics: emerging problem and future
      strategies.
AB  - AIMS AND OBJECTIVES: To evaluate the magnitude of red cell alloimmunization in
      regularly transfused patients with thalassemia major and analyse factors
      responsible for development of antibodies. MATERIALS AND METHODS: This cross
      sectional study was conducted on 116 thalassemics receiving regular transfusions.
      All the patients underwent antibody screening. Patients with positive antibody
      screen were further tested for antibody identification. The data was analysed to
      find out the frequency, pattern and factors influencing red cell alloimmunization
      secondary to multiple transfusions. RESULTS: Mean age of the patients was 14
      years (range 1.5-27 years). Red cell alloantibodies were found in 11 patients
      (9.48%). In four (36%) patients first transfusion was given before 6 months of
      age and in seven (64%) patients, first transfusion was given after two years of
      age. The interval between consecutive transfusions varied from 18 to 35 days. The
      most common antibody was Anti-E found in 4 (36.4%) patients, followed by Anti-K
      (three patients, 27.2%), Anti-Kp(a) (two patients, 18.2%) and Anti-C(w) (two
      patients, 18.2%). The interval from first transfusion to antibody development
      varied from 1.5 to 14 years. None of the eight out of 116 patients, who underwent
      splenectomy showed any antibody development. CONCLUSIONS: The rate of red cell
      alloimmunization was found to be 9.48% in thalassemics receiving regular
      transfusions. The incidence of alloantibody development was higher if first
      transfusion was received at more than 2 years of age. Early institution of red
      cell transfusions and Rh and Kell phenotyping followed by provision of matched
      blood could prevent alloimmunization.

PMID- 21856232
TI  - Malaria morbidity and pyrethroid resistance after the introduction of insecticide
      treated bednets and artemisinin-based combination therapies: a longitudinal
      study.
AB  - BACKGROUND: Substantial reductions in malaria have been reported in several
      African countries after distribution of insecticide-treated bednets and the use
      of artemisinin-based combination therapies (ACTs). Our aim was to assess the
      effect of these policies on malaria morbidity, mosquito populations, and
      asymptomatic infections in a west African rural population. METHODS: We did a
      longitudinal study of inhabitants of Dielmo village, Senegal, between January,
      2007, and December, 2010. We monitored the inhabitants for fever during this
      period and we treated malaria attacks with artesunate plus amodiaquine. In July,
      2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to
      all villagers. We did monthly night collections of mosquitoes during the whole
      study period, and we assessed asymptomatic carriage from cross-sectional surveys.
      Our statistical analyses were by negative binomial regression, logistic
      regression, and binomial or Fisher exact test. FINDINGS: There were 464 clinical
      malaria attacks attributable to Plasmodium falciparum during 17,858 person-months
      of follow-up. The incidence density of malaria attacks averaged 5.45 (95% CI 4.90
      6.05) per 100 person-months between January, 2007, and July, 2008, before the
      distribution of LLINs. Incidence density decreased to 0.41 (0.29-0.55) between
      August, 2008, and August, 2010, but increased back to 4.57 (3.54-5.82) between
      September and December, 2010--ie, 27-30 months after the distribution of LLINs.
      The rebound of malaria attacks were highest in adults and children aged 10 years
      or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%)
      of 384 in 2007 and 2008 (p<0.0001). 37% of Anopheles gambiae mosquitoes were
      resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr
      resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0.0009).
      INTERPRETATION: Increasing pyrethroid resistance of A gambiae and increasing
      susceptibility of older children and adults, probably due to decreasing immunity,
      caused the rebound and age shift of malaria morbidity. Strategies to address the
      problem of insecticide resistance and to mitigate its effects must be urgently
      defined and implemented. FUNDING: Institut de Recherche pour le Developpement and
      the Pasteur Institute of Dakar.

PMID- 21856233
TI  - Epidemiology of malaria morbidity after control scale-up.

PMID- 21856234
TI  - Clinical aspects of testicular microlithiasis in boys: a review.
AB  - OBJECTIVE: After review of the pediatric literature, we report on the prevalence
      of testicular microlithiasis and its relation with benign and malign entities. We
      provide a guideline for the management of boys with testicular microlithiasis.
      MATERIALS AND METHODS: The databases searched were Medline, Web of Science,
      Embase and the Cochrane Library. Data on the rates of testicular microlithiasis
      were collected and from each study information was extracted on the study
      population according to country, study design, diagnostic method, type of
      patient, number of patients, age, associated anomalies, additional diagnostic
      methods and follow-up information. From the 472 articles, we selected 126
      articles as potentially relevant, of which 57 were included. RESULTS: In
      asymptomatic boys, the prevalence of testicular microlithiasis is 4.2% and in
      symptomatic referrals it is 1.6%. The development of a testicular malignancy is
      occasionally reported after diagnosis of testicular microlithiasis. The
      management of boys with testicular microlithiasis varies widely. Most authors
      recommend regular self-examination, and some perform testicular ultrasound and/or
      screen tumor markers. CONCLUSION: The prevalence of testicular microlithiasis in
      boys varies between 1.1% and 4.2%. For follow-up, regular self-examination is
      advised from the age of 15 years.

PMID- 21856235
TI  - Complete urethral duplication: description of surgical approach mimicking distal
      epispadias repair.
AB  - OBJECTIVE: To present two cases of type IIA urethral duplication and propose a
      reproducible surgical approach. METHODS: Two cases are presented in this report.
      The first was a male child with a type IIA1 urethral duplication with two
      urethral channels arising from the bladder through separate bladder necks
      coursing to the glans penis. The second infant had a type IIA2 urethral
      duplication with a single bladder neck. Both children were repaired using a
      surgical approach that joined both urethral openings into a single orthopic
      meatus. This was accomplished by incising the common septum and utilizing
      techniques similar to that of a distal epispadias repair. RESULTS: At six months
      of follow-up both infants are voiding from a single stream without complication.
      Long-term outcomes remain to be determined. CONCLUSIONS: The technique presented
      in this report both functionally and cosmetically unites the two urethral
      meatuses while eliminating the risk of damage to the sphincter.

PMID- 21856236
TI  - Cutaneous leishmaniasis in British troops following jungle training in Belize.
AB  - British military personnel account for 45% of cutaneous leishmaniasis (CL) cases
      seen in the UK and 103 cases from Belize were seen in 1998-2009. Systemic
      treatment of CL from Belize should not be considered essential in immunocompetent
      patients because mucosal leishmaniasis very rarely occurs.

PMID- 21856237
TI  - Ictal characteristics of psychogenic nonepileptic seizures: what we have learned
      from video/EEG recordings--a literature review.
AB  - Psychogenic nonepileptic seizures (PNES) are highly prevalent in selected
      populations, with a strong impact in terms of morbidity and social cost. The gold
      standard for PNES diagnosis is video/EEG recording of a typical attack. However
      this technique is costly and not always available. In addition, many patients are
      treated with antiepileptic drugs for several years before undergoing video/EEG
      recording. The diagnosis is further complicated by concomitant epileptic seizures
      in some patients with PNES. Therefore, a good knowledge of PNES semiology is
      important for early screening of patients for video/EEG recording and for correct
      interpretation of the examination. We reviewed the literature on video/EEG
      studies reporting ictal PNES semiology to identify features indicative of
      psychogenic or epileptic seizures. Several features appeared to be useful in the
      clinical setting.

PMID- 21856238
TI  - Ethical issues in surgical decision making concerning children with medically
      intractable epilepsy.
AB  - The widespread inclusion of surgical strategies in the treatment of medically
      intractable epilepsy is largely justified by the medical and psychosocial burden
      of the illness. Performing these procedures in pediatric populations is
      associated with distinct challenges ranging from unique seizure etiologies to
      issues surrounding brain development and functional plasticity. As the trend
      toward more aggressive surgical intervention continues, the ethical foundation of
      current and emerging practices must be increasingly scrutinized. Here, we present
      the first article discussing ethical issues in the surgical management of
      medically intractable epilepsies in children. We discuss principles of informed
      consent, harm reduction, and justice in this vulnerable patient population. We
      also highlight the unique ethical challenge of surgical decision making
      concerning developmentally delayed children. The recognition of these issues is
      essential to providing patient-centered, responsible, and ethical care.

PMID- 21856239
TI  - The prognostic significance of lymphovascular invasion on biopsy specimens in
      lung cancer treated with definitive chemoradiotherapy.
AB  - PURPOSE: This study aims to determine prognostic factors for patients who have
      non-small-cell lung cancer (NSCLC) that is treated with definitive chemoradiation
      therapy. MATERIALS AND METHODS: Seventy-eight patients has been treated with
      radiation therapy and concomitant or sequential chemotherapy between 2000 and
      2005. Paraffin-embedded biopsy specimens were obtained before treatment from 73
      patients and reviewed by two independent pathologists. Complete follow-up data
      were collected. The impact of clinical and pathological factors and treatment
      modality on survival was studied using the chi(2) and Fisher exact tests. A
      multivariate analysis was performed using the Cox proportional hazard model.
      RESULTS: Seventy-three patients were evaluated, 58 men and 15 women. Median age
      was 62 years. Most had locally advanced disease (42 stage IIIB and 24 stage
      IIIA), whereas 7 were medically inoperable stage I-II patients. Lymphovascular
      invasion (LVI) was identified in 20 biopsy specimens (27.4 %). Radiotherapy
      delivered a median dose of 66 Gy (range, 60 to 70 Gy). The median overall
      survival was 20.5 months. Relapse-free and overall survival were significantly
      higher in the concomitant arm than in the sequential arm (P = .025 and P = .031,
      respectively). We found an independent association between the presence of LVI
      and both the risk of death with an adjusted hazard ratio (HR) of 2.69 (95%
      confidence interval [CI] 1.50-4.83) and the risk of metastatic progression
      (adjusted HR = 3.01; 95% CI 1.58-5.72). CONCLUSION: The presence of LVI on stage
      III NSCLC biopsy specimens was the only independent prognostic factor for poor
      outcome and may, therefore, be helpful in identifying patients at high risk of
      metastatic disease.

PMID- 21856240
TI  - Anticholinergic medications and cognition.

PMID- 21856241
TI  - Primary care practitioners on the front line of Alzheimer's disease care.

PMID- 21856242
TI  - The specificity of geriatric rehabilitation: myth or reality? A debate from an
      italian perspective.

PMID- 21856243
TI  - Sarcopenia and mortality among older nursing home residents.
AB  - BACKGROUND AND AIMS: Sarcopenia has been indicated as a reliable marker of
      frailty and poor prognosis among the oldest individuals. At present, no data are
      available on sarcopenia in the nursing home population. The aim of the current
      study was to explore the relationship between sarcopenia and all-cause mortality
      in a population of elderly persons aged 70 years and older living in a nursing
      home in Italy. METHODS: This study was conducted among all subjects (n = 122)
      aged 70 years and older who lived in the teaching nursing home of Catholic
      University of Rome between August 1, 2010, and September 30, 2010. According to
      the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was
      diagnosed in presence of low muscle mass plus either low muscle strength or low
      physical performance. The primary outcome measure was survival after 6 months.
      RESULTS: Forty residents (32.8%) were indentified as affected by sarcopenia. This
      condition was more common in men (68%) than in women (21%). During the follow-up
      period, 26 (21.3%) patients died. After adjusting for age, gender,
      cerebrovascular diseases, osteoarthritis, chronic obstructive pulmonary disease,
      activity of daily living impairment, and body mass index, residents with
      sarcopenia were more likely to die compared with those without sarcopenia
      (adjusted hazard ratio 2.34; 95% confidence interval 1.04-5.24). CONCLUSIONS: The
      present study suggests that among subjects living in a nursing home, sarcopenia
      is highly prevalent and is associated with a significantly increased risk of all
      cause death. The current findings support the possibility that sarcopenia has an
      independent effect on survival among nursing home residents.

PMID- 21856244
TI  - Psychosocial assessment of nursing home residents via MDS 3.0: recommendations
      for social service training, staffing, and roles in interdisciplinary care.
AB  - The Minimum Data Set 3.0 has introduced a higher set of expectations for
      assessment of residents' psychosocial needs, including new interviewing
      requirements, new measures of depression and resident choice, and new discharge
      screening procedures. Social service staff are primary providers of psychosocial
      assessment and care in nursing homes; yet, research demonstrates that many do not
      possess the minimum qualifications, as specified in federal regulations, to
      effectively provide these services given the clinical complexity of this client
      population. Likewise, social service caseloads generally exceed manageable
      levels. This article addresses the need for enhanced training and support of
      social service and interdisciplinary staff in long term care facilities in light
      of the new Minimum Data Set 3.0 assessment procedures as well as new survey and
      certification guidelines emphasizing quality of life. A set of recommendations
      will be made with regard to training, appropriate role functions within the
      context of interdisciplinary care, and needs for more realistic staffing ratios.

PMID- 21856245
TI  - Dose-adjusting capecitabine minimizes adverse effects while maintaining efficacy:
      a retrospective review of capecitabine for metastatic breast cancer.
AB  - Capecitabine monotherapy is considered standard treatment in anthracycline- and
      taxane-pretreated metastatic breast cancer and has proven efficacy in this
      setting. Randomized studies and retrospective analyses have shown that, in
      patients who received capecitabine monotherapy, or in combination with docetaxel,
      dose modification of capecitabine is effective in the management of adverse
      events without compromising efficacy. Dose adjustment of capecitabine is easy to
      implement due to its twice-daily oral administration. This article reports the
      findings of a retrospective review of a large data set to consolidate the
      information about the impact of capecitabine dose modification on efficacy and
      safety outcomes in patients with metastatic breast cancer. Data on dose
      modification and outcomes were available from 4 phase II capecitabine monotherapy
      trials, 1 phase III capecitabine/docetaxel combination trial, and an analysis of
      consecutive patients who received capecitabine outside of a clinical trial (n =
      971). Dose reductions were required in 41% of patients who received monotherapy
      (n = 131) and 65% of patients who received capecitabine/docetaxel (80% of these
      required dose reductions of both agents) (n = 163). Time to disease progression
      and overall survival were similar, or even slightly longer, among patients who
      received lower vs. full-dose capecitabine in all of the studies reviewed. Reduced
      capecitabine doses were associated with a lower incidence of treatment-related
      adverse events, specifically hand-foot syndrome, diarrhea, and stomatitis.
      Together, these data support the practice of dose-reducing capecitabine,
      including the possibility of starting at a lower dose (<1250 mg/m(2) twice
      daily), to reduce the incidence of adverse events without compromising efficacy.

PMID- 21856246
TI  - Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal
      polarization.
AB  - Directed membrane trafficking is believed to be crucial for axon development
      during neuronal morphogenesis. However, the underlying mechanisms are poorly
      understood. Here, we report a role of Lgl1, the mammalian homolog of Drosophila
      tumor suppressor Lethal giant larvae, in controlling membrane trafficking
      underlying axonal growth. We find that Lgl1 is associated with plasmalemmal
      precursor vesicles and enriched in developing axons. Lgl1 upregulation promoted
      axonal growth, whereas downregulation attenuated it as well as directional
      membrane insertion. Interestingly, Lgl1 interacted with and activated Rab10, a
      small GTPase that mediates membrane protein trafficking, by releasing GDP
      dissociation inhibitor (GDI) from Rab10. Furthermore, Rab10 lies downstream of
      Lgl1 in axon development and directional membrane insertion. Finally, both Lgl1
      and Rab10 are required for neocortical neuronal polarization in vivo. Thus, the
      Lgl1 regulation of Rab10 stimulates the trafficking of membrane precursor
      vesicles, whose fusion with the plasmalemma is crucial for axonal growth.

PMID- 21856247
TI  - Rurality and other factors associated with adherence to immunosuppressant
      medications in community-dwelling solid-organ transplant recipients.
AB  - BACKGROUND: Data on immunosuppressant adherence of community-dwelling adult solid
      organ transplant recipients (SOTRs) from rural populations in the United States
      are limited. Therefore, understanding the association of rurality and other
      factors of immunosuppressant adherence will help providers design and deliver
      patient-centered adherence enhancing interventions. OBJECTIVES: The objective was
      to examine factors associated with a previously validated 4-item
      Immunosuppressant Therapy Adherence Scale (ITAS) score in community-dwelling
      adult SOTRs who received a transplant from an academic center in the Midwestern
      United States. METHODS: For this observational study, cross-sectional survey data
      (patient demographic, medical condition, immunosuppressant therapy, and self
      reported ITAS) received from adult SOTRs aged 19 years or older with other data
      from an academic transplant center's database were merged. Using multivariate
      logistic regression, significant SOTR characteristics associated with being
      adherent (ITAS score=12) versus nonadherent (ITAS score <12) were examined.
      RESULTS: The survey response rate was 30% (n=556/1827). Those SOTRs responding
      (n=556) had a kidney (48%), liver (47%), or other (4.5%) transplant. They were
      more likely to be 50- to 64-year olds (52%), men (55%), white (90%),
      metroresident (59%), with an annual income less than $55,000. The SOTRs were
      living with a transplant for 6.3 years (median), reported excellent-to-good
      health status (77%), and received different immunosuppressant regimens. More than
      half of the SOTRs (58%) were adherent. In multivariate analyses, compared with
      patients aged 65 years or older, younger patients, nonmetro rural- versus
      metroresident, and those having more (>=6) versus less (<6) comorbidities were
      significantly less likely to report adherence. SOTRs receiving tacrolimus-based
      combination immunosuppressant versus tacrolimus alone were more likely to report
      adherence. CONCLUSIONS: When designing and delivering patient care-centered
      interventions including those that use technology to increase immunosuppressant
      adherence, providers need to consider rural residence besides other well
      established patient factors (younger age, immunosuppressant drug, and
      comorbidities) of nonadherence.

PMID- 21856248
TI  - Dethrombosis of lower extremity thrombus by local delivery of thrombolysis using
      ClearWay transcatheter balloon irrigation: a feasibility study.
AB  - BACKGROUND: Thrombus is highly prevalent in patients with recent symptoms (<6
      months) of claudication or limb ischemia with occluded culprit lower extremity
      arterial vessels. Treatment of these thrombotic occlusions is challenging. In
      this feasibility study, the Vascular ClearWay Irrigating PTFE Balloon Catheter
      (Atrium, Husdson, NH, USA) has been tested for its safety and ability to dissolve
      thrombus in patients with recent arterial occlusions. METHODS: Twenty consecutive
      patients with lower extremity occlusion were prospectively enrolled to test the
      feasibility of the ClearWay balloon irrigation system. Cohorts of five patients
      were tested with increasing doses of tPA (five control patients with saline, five
      patients with 0.25 mg/cm, five patients with 0.4 mg/cm and five patients with 0.6
      mg/cm of lesion length). Volumetric intravascular ultrasound core laboratory
      assessment of the thrombus was performed at baseline and after ClearWay
      thrombolysis (but prior to definitive treatment of the vessel with other
      debulking or stenting) to evaluate the effectiveness of ClearWay to remove
      thrombus. RESULTS: Twenty consecutive patients were enrolled in this study (11
      men; mean age, 68.54 +/- 8.15 years), and 14 had volumetric intravascular
      ultrasound available both before and after Clearway. Based on patients' symptom
      onset, 1 patient was acute (< 24 h), 4 subacute (> 24 h, < 30 days) and 15
      chronic (between 1 and 6 months). There were no safety events as predefined by
      the protocol including no major bleeding, death, distal embolization distal to
      the filter, acute renal failure or vascular complications. Acute procedural
      success was seen in 100% of cases. There were no statistical difference in plaque
      thrombus volume between baseline (pretreatment) and control ClearWay treatment
      (saline infusion; P = .911, n = 4). Also, there was no statistical difference in
      plaque-thrombus volume between pretreatment baseline and ClearWay tPA treatment
      (P = .628, n = 14). Following Angiojet rheolytic thrombectomy (n = 8 patients)
      post-ClearWay lytic treatment, there was a statistical reduction of plaque
      thrombus volume versus ClearWay lytic treatment alone (P = .030) or pretreatment
      baseline (P = .029). There were no deaths or amputations. Macrodebris > 2 mm were
      present in 50% of patients captured by embolic filter protection. In-hospital
      reocclusion of the treated vessel occurred in one patient (5%) and 30-day
      reocclusion occurred in two patients (10%) on follow-up. CONCLUSION: Using the
      ClearWay to deliver lytic therapy appears safe in this small feasibility study.
      Although lytic treatment with the ClearWay balloon alone did not demonstrate
      reduction in plaque-thrombus volume in this small population, the use of Angiojet
      rheolytic thrombectomy following ClearWay did reduce plaque volume. Further data
      are needed to address definitive effects of ClearWay balloon alone and utility to
      facilitate Angiojet thromboreduction.

PMID- 21856249
TI  - Ranolazine for the treatment of refractory angina in a veterans population.
AB  - BACKGROUND: Pivotal ranolazine trials did not require optimization of
      conventional medical therapy including coronary revascularization and antianginal
      drug therapy prior to ranolazine use. This case series describes the use of
      ranolazine for the treatment of chronic stable angina refractory to maximal
      medical treatment in a veterans population. RESULTS: A total of 18 patients with
      a median age of 66 years were identified. All patients had prior percutaneous
      coronary intervention and/or coronary artery bypass graft surgery; 83% had three
      vessel coronary artery disease, with left main disease present in 39% of
      patients. Prior to initiating ranolazine, antianginal use consisted of beta
      blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%).
      Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were
      controlled. Median preranolazine angina episodes and sublingual nitroglycerin
      (SLNTG) doses per week were 14 and 10, respectively, with a Canadian
      Cardiovascular Society (CCS) angina grade of III-IV in 67% of patients. After
      initiation of ranolazine, median angina episodes per week and SLNTG doses used
      per week decreased to 0.7 and 0, respectively, with CCS grade of III-IV declining
      to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina
      episodes. CONCLUSION: The addition of ranolazine to maximally tolerated
      conventional antianginal drug therapy post coronary revascularization was
      associated with decreases in angina episodes and SLNTG utilization and
      improvement in CCS angina grades. Ranolazine may provide an effective treatment
      option for revascularized patients with refractory angina.

PMID- 21856250
TI  - Acute myocardial infarction and cardiac arrest due to coronary artery perforation
      after mitral valve surgery: successful treatment with a covered stent.
AB  - We present a case of a gentleman who presented with acute myocardial infarction
      and cardiac arrest 6 days after undergoing mitral valve replacement surgery.
      Immediate coronary angiography revealed perforation of the left circumflex artery
      which was successfully treated with a covered stent. This report details the
      successful percutaneous treatment of an exceedingly rare complication of mitral
      valve surgery.

PMID- 21856251
TI  - Takotsubo cardiomyopathy: reversible elevation in microcirculatory resistance.
AB  - We present a case of takotsubo cardiomyopathy and demonstrate an initial
      elevation of microcirculatory resistance (IMR) that reduced on follow-up
      evaluation. This corresponded with improvements in left ventricular function. We
      postulate that the changes in microvascular resistance reflect favourable left
      ventricular microvascular remodelling. The measurement of IMR, a novel marker of
      microcirculatory dysfunction, provides novel insights into the pathophysiology of
      this condition.

PMID- 21856252
TI  - Nucleoside analogue electrochemical behaviour and in situ evaluation of DNA
      clofarabine interaction.
AB  - Nucleoside analogues have had a substantial impact on the treatment of cancer,
      especially haematological malignancies. The electrochemical behaviour of the
      nucleoside analogue clofarabine (CLF) was investigated at a glassy carbon
      electrode using cyclic, differential pulse and square wave voltammetry in
      different pH supporting electrolytes. The oxidation process of CLF is
      irreversible and pH-dependent with transfer of two protons and two electrons,
      following a diffusion controlled mechanism. The oxidation mechanism of CLF
      involves deprotonation and leads to the formation of a hydroxylated species that
      undergoes reversible redox reactions. The interaction of DNA and the antileukemia
      drug CLF was investigated using a dsDNA-electrochemical biosensor in incubated
      solutions by differential pulse voltammetry. The CLF-DNA interaction leads to
      changes in the DNA morphological structure, confirmed using the purinic homo
      polynucleotide single stranded sequences of guanosine and adenosine, poly[G] and
      poly[A]-electrochemical biosensors.

PMID- 21856253
TI  - Metabolic and pharmacokinetic studies of curcumin, demethoxycurcumin and
      bisdemethoxycurcumin in mice tumor after intragastric administration of
      nanoparticle formulations by liquid chromatography coupled with tandem mass
      spectrometry.
AB  - This paper aims to investigate the metabolism and pharmacokinetics of curcumin,
      demethoxycurcumin and bisdemethoxycurcumin in mice tumor. To improve water
      solubility, nanoparticle formulations were prepared as curcuminoids-loaded solid
      lipid nanoparticles (curcuminoids-SLNs) and curcumin-loaded solid lipid
      nanoparticles (curcumin-SLNs). After intragastric administration to tumor-bearing
      ICR mice, the plasma and tumor samples were analyzed by liquid chromatography
      with ion trap mass spectrometry. We discovered that curcuminoids were mainly
      present as glucuronides in plasma, whereas in free form in tumor tissue. A
      validated LC/MS/MS method was established to determine the three free
      curcuminoids in tumor homogenate. Samples were separated on a Zorbax SB-C(18)
      column, eluted with acetonitrile-water (containing 0.1% formic acid), and
      detected by TSQ Quantum triple quadrupole mass spectrometer in selected reaction
      monitoring mode. The method showed good linearity (r(2)=0.997-0.999) over wide
      dynamic ranges (2-6000 ng/mL). Variations within- and between-batch never
      exceeded 11.2% and 13.4%, respectively. The extraction recovery rates ranged from
      78.3% to 87.7%. The pharmacokinetics of curcuminoids in mice tumor fit two
      compartment model and first order elimination. For curcumin-SLNs group, the
      dosing of 250 mg/kg of curcumin resulted in AUC((0-48 h)) of 2285 ngh/mL and
      C(max) of 209 ng/mL. For curcuminoids-SLNs group, the dosing equivalent to 138
      mg/kg of curcumin resulted in higher tumor concentrations (AUC=2811 ngh/mL,
      C(max)=285 ng/mL). It appeared that co-existing curcuminoids improved the
      bioavailability of curcumin.

PMID- 21856254
TI  - A quantitative LC-MS/MS method for comparative analysis of capture-antibody
      affinity toward protein antigens.
AB  - A mass spectrometry-based antibody selection procedure was developed to evaluate
      optimal 'capture' monoclonal antibodies that can be used in a variety of
      analytical measurement applications. The isotope-dilution liquid chromatography
      tandem mass spectrometry (ID LC-MS/MS) methodology is based on the use of
      multiple-reaction monitoring of tryptic peptide fragments derived from protein
      antigens. A panel of monoclonal antibodies (mAb) was evaluated based on a
      quantitative determination of relative binding affinity to human cardiac troponin
      I following immunoprecipitation. Dissociation constants (K(d)) were determined
      for 'bound mAb-antigen' vs. 'unbound antigen' using non-linear regression
      analysis. Relative quantification of both antigen and antibody was based on the
      use of stable isotope-labeled synthetic peptides as internal standards. Optimal
      'capture' mAbs were determined through evaluation of relative K(d) constants of
      all monitored peptide transitions. A panel of six pre-screened candidate capture
      mAbs was concluded to consist of two subsets of mAbs, each with statistically
      equivalent K(d) constants as determined using NIST Standard Reference Material
      (SRM) 2921 - Human Cardiac Troponin Complex. This ID LC-MS/MS method is shown to
      be capable of quantitatively differentiating mAbs based on relative binding
      affinities. Selection of optimal capture mAbs can be applied toward a number of
      analytical applications which require metrological traceability and unbiased
      quantification.

PMID- 21856255
TI  - Quantitative analysis of myo-inositol in urine, blood and nutritional supplements
      by high-performance liquid chromatography tandem mass spectrometry.
AB  - Myo-inositol plays key physiological functions, necessitating development of
      methodology for quantification in biological matrices. Limitations of current
      mass spectrometry-based approaches include the need for a derivatisation step
      and/or sample clean-up. In addition, co-elution of glucose may cause ion
      suppression of myo-inositol signals, for example in blood or urine samples. We
      describe an HPLC-MS/MS method using a lead-form resin based column online to a
      triple quadrupole tandem mass spectrometer, which requires minimum sample
      preparation and no derivatisation. This method allows separation and selective
      detection of myo-inositol from other inositol stereoisomers. Importantly,
      inositol was also separated from hexose monosaccharides of the same molecular
      weight, including glucose, galactose, mannose and fructose. The inter- and intra
      assay variability was determined for standard solutions and urine with inter
      assay coefficient of variation (CV) of 1.1% and 3.5% respectively, while intra
      assay CV was 2.3% and 3.6%. Urine and blood samples from normal individuals were
      analysed.

PMID- 21856256
TI  - Enantioselective determination of 3-hydroxybutyrate in the tissues of normal and
      streptozotocin-induced diabetic rats of different ages.
AB  - L-3-Hydroxybutyrate (3HB) and D-3HB are enantiomers that exist in various rat
      tissues, and the ratio of the 2 compounds is of importance since it may affect
      glucose utilization in cardiomyocytes. In this study, we determined the
      concentrations of L-3HB and D-3HB in the tissues of normal and streptozotocin
      (STZ)-induced diabetic rats of different ages by column-switching high
      performance liquid chromatography using a fluorescence detection system. In
      normal rats, the levels of L-3HB peaked at 8 weeks of age in the cerebrum, liver,
      spleen, lung, kidney, adrenal gland, and heart and then decreased afterwards. The
      concentrations of L-3HB were the highest in the heart, with 26.24+/-13.74
      MUmol/mg protein. In addition, there was an increase in the levels of (D+L)-3HB,
      D-3HB, and L-3HB in the tissues of diabetic rats with time, whereas the ratios of
      L-3HB to (D+L)-3HB declined (46.44% vs. 21.03%, P<0.05, in heart tissue after 24
      weeks of STZ treatment). Both the concentration and the ratio of L-3HB may be
      associated with disease conditions, and the determination of L-3HB may help
      clarify the role of L-3HB under physiological and pathological conditions.

PMID- 21856257
TI  - Characterization of DOK1, a candidate tumor suppressor gene, in epithelial
      ovarian cancer.
AB  - In attempt to discover novel aberrantly hypermethylated genes with putative tumor
      suppressor function in epithelial ovarian cancer (EOC), we applied expression
      profiling following pharmacologic inhibition of DNA methylation in EOC cell
      lines. Among the genes identified, one of particular interest was DOK1, or
      downstream of tyrosine kinase 1, previously recognized as a candidate tumor
      suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite
      sequencing, we determined that a 5'-non-coding DNA region (located at nt -1158 to
      -850, upstream of the DOK1 translation start codon) was extensively
      hypermethylated in primary serous EOC tumors compared with normal ovarian
      specimens; however, this hypermethylation was not associated with DOK1
      suppression. On the contrary, DOK1 was found to be strongly overexpressed in
      serous EOC tumors as compared to normal tissue and importantly, DOK1
      overexpression significantly correlated with improved progression-free survival
      (PFS) values of serous EOC patients. Ectopic modulation of DOK1 expression in EOC
      cells and consecutive functional analyses pointed toward association of DOK1
      expression with increased EOC cell migration and proliferation, and better
      sensitivity to cisplatin treatment. Gene expression profiling and consecutive
      network and pathway analyses were also confirmative for DOK1 association with EOC
      cell migration and proliferation. These analyses were also indicative for DOK1
      protective role in EOC tumorigenesis, linked to DOK1-mediated induction of some
      tumor suppressor factors and its suppression of pro-metastasis genes. Taken
      together, our findings are suggestive for a possible tumor suppressor role of
      DOK1 in EOC; however its implication in enhanced EOC cell migration and
      proliferation restrain us to conclude that DOK1 represents a true TSG in EOC.
      Further studies are needed to more completely elucidate the functional
      implications of DOK1 and other members of the DOK gene family in ovarian
      tumorigenesis.

PMID- 21856259
TI  - Endoscopic treatment of a large post-surgical fistula using combined fibrin glue
      spray and vicryl mesh.

PMID- 21856258
TI  - Clinical features of 20 patients with curatively resected biliary neuroendocrine
      tumours.
AB  - BACKGROUND: Neuroendocrine tumours very rarely occur in the biliary tract;
      information about them is limited. AIMS: To present the clinical characteristics
      and prognosis of curatively resected biliary neuroendocrine tumours. METHODS:
      Review of medical records dated between 2000 and 2010 of 20 patients from three
      medical centres with biliary neuroendocrine tumour based on curative resection.
      RESULTS: Based on the World Health Organization 2010 classification, five and one
      patients had neuroendocrine tumour grades 1 and 2, seven had neuroendocrine
      carcinoma, and seven were diagnosed with mixed adenoneuroendocrine carcinoma. The
      locations were the following: seven in the gallbladder, four in the extrahepatic
      bile duct, and nine in the ampulla of Vater. Lymph node and hepatic metastases
      were noted in 11 and 4 patients, respectively. Fourteen patients experienced
      recurrence; most had recurrence in the liver. Patients with neuroendocrine tumour
      grade 1 had a lower rate of recurrence compared to others (p=0.001). The median
      disease-free and overall survival times were 5.8 (0.4-53.6) and 13.7 (1.9-102.1)
      months for all four subtypes. However, the median disease free and overall
      survival rates of neuroendocrine tumours were significantly longer than those of
      neuroendocrine carcinomas or mixed adenoneuroendocrine carcinoma. CONCLUSIONS:
      Patients with biliary neuroendocrine tumour showed extremely different clinical
      outcomes according to histopathologic subtypes by World Health Organization 2010
      classification.

PMID- 21856260
TI  - Comment on "the role of endoscopic ultrasound in the evaluation of chronic
      mesenteric ischaemia".

PMID- 21856261
TI  - Developing a Core Competency Model and Educational Framework for Primary
      Maternity Services: a national consensus approach.
AB  - BACKGROUND: An appropriately educated and competent workforce is crucial to an
      effective health care system. The National Health Workforce Taskforce (now Health
      Workforce Australia) and the Maternity Services Inter-Jurisdictional Committee
      funded a project to develop Core Competencies and Educational Framework for
      Primary Maternity Services in Australia. These competencies recognise the
      interdisciplinary nature of maternity care in Australia where care is provided by
      general practitioners, obstetricians and midwives as well as other professionals.
      PARTICIPANTS: Key stakeholders from professional organisations and providers of
      services related to maternity care and consumers of services. METHODS: A national
      consensus approach was undertaken using consultation processes with a Steering
      Committee, a wider Reference Group and public consultation. FINDINGS: A national
      Core Competencies and Educational Framework for Primary Maternity Services in
      Australia was developed through an iterative process with a range of key
      stakeholders. There are a number of strategies that may assist in the integration
      of these into primary maternity service provider professional groups' education
      and practice. CONCLUSIONS: The Core Competencies and Educational Framework are
      based on an interprofessional approach to learning and primary maternity service
      practice. They have sought to value professional expertise and stimulate
      awareness and respect for the roles of all primary maternity service providers.
      The competencies and framework described in this paper are now a critical
      component of Australian maternity services as they are included in actions in the
      newly released National Maternity Services Plan and thus have relevance for all
      providers of Australian maternity services.

PMID- 21856262
TI  - Infections in the operated spine: update on risk management and therapeutic
      strategies.
AB  - Among the possible risks of spine surgery, surgical site infection (SSI) is far
      from negligible. Incidence is higher than in other locomotor system procedures,
      with more severe local and general impact. Certain broad guidelines can be
      formulated. The risk of SSI should be taken into account in the choice of
      treatment options discussed with the patient. Antibiotic prophylaxis, surgical
      prevention of iatrogenic infection and an SSI surveillance protocol should be
      implemented. SSI should be suspected in case of any abnormality in postoperative
      course, and biological and imaging (MRI or CT) measures should be taken. Local
      sampling for bacteriological identification is mandatory. Treatment strategy
      should ideally be discussed in a multidisciplinary coordination meeting, and
      adapted in the light of local bacterial ecology and resistance data. The
      information provided to the patient should be transparent and adapted to the
      patient's individual context. LEVEL OF EVIDENCE: Level V.

PMID- 21856264
TI  - Estimation of disease prevalence, true positive rate, and false positive rate of
      two screening tests when disease verification is applied on only screen
      positives: a hierarchical model using multi-center data.
AB  - OBJECTIVES: A model is proposed to estimate and compare cervical cancer screening
      test properties for third world populations when only subjects with a positive
      screen receive the gold standard test. Two fallible screening tests are compared,
      VIA and VILI. METHODS: We extend the model of Berry et al. [1] to the multi-site
      case in order to pool information across sites and form better estimates for
      prevalences of cervical cancer, the true positive rates (TPRs), and false
      positive rates (FPRs). For 10 centers in five African countries and India
      involving more than 52,000 women, Bayesian methods were applied when gold
      standard results for subjects who screened negative on both tests were treated as
      missing. The Bayesian methods employed suitably correct for the missing screen
      negative subjects. The study included gold standard verification for all cases,
      making it possible to validate model-based estimation of accuracy using only
      outcomes of women with positive VIA or VILI result (ignoring verification of
      double negative screening test results) with the observed full data outcomes.
      RESULTS: Across the sites, estimates for the sensitivity of VIA ranged from 0.792
      to 0.917 while for VILI sensitivities ranged from 0.929 to 0.977. False positive
      estimates ranged from 0.056 to 0.256 for VIA and 0.085 to 0.269 for VILI. The
      pooled estimates for the TPR of VIA and VILI are 0.871 and 0.968, respectively,
      compared to the full data values of 0.816 and 0.918. Similarly, the pooled
      estimates for the FPR of VIA and VILI are 0.134 and 0.146, respectively, compared
      to the full data values of 0.144 and 0.146. Globally, we found VILI had a
      statistically significant higher sensitivity but no statistical difference for
      the false positive rates could be determined. CONCLUSION: Hierarchical Bayesian
      methods provide a straight forward approach to estimate screening test
      properties, prevalences, and to perform comparisons for screening studies where
      screen negative subjects do not receive the gold standard test. The hierarchical
      model with random effects used to analyze the sites simultaneously resulted in
      improved estimates compared to the single-site analyses with improved TPR
      estimates and nearly identical FPR estimates to the full data outcomes.
      Furthermore, higher TPRs but similar FPRs were observed for VILI compared to VIA.

PMID- 21856265
TI  - Multiple myeloma associated IgA pemphigus: treatment with bortezomib- and
      lenalidomide-based regimen.

PMID- 21856266
TI  - Pancreatic mucinous cystadenoma in an adult with cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most frequent genetic disease in the Caucasian
      population. It seems to be associated with an increased risk of digestive cancer
      but only few cases of pancreatic tumors have been reported. As pancreatic lesions
      of the pancreas in CF patients are not rare, their etiological diagnosis is
      substantial. We report herein a case of a mucinous cystadenoma in a patient with
      CF. Diagnosis and management of pancreatic cystic tumors in patients at high risk
      of operative morbidity are challenging. When the potential malignancy of a
      pancreatic cystic mass cannot be well established in a CF patient, partly because
      of frequent chronic pancreatitis lesions, we suggest that surgical management
      should be undertaken instead of radiological surveillance.

PMID- 21856267
TI  - Efficacy of vitamins supplementation to therapy on Helicobacter pylori
      eradication in patients with low antioxidant capacity.
AB  - BACKGROUND AND OBJECTIVES: It was shown that supplementation of vitamins C and E
      to therapy increased Helicobacter pylori eradication rate. In the present study,
      we aimed to evaluate whether supplementation of antioxidant vitamins to therapy
      increases H. pylori eradication rates in patients with chronic stress and low
      antioxidant capacity. METHODS: This study included 120 patients who presented to
      gastroenterology outpatient clinic with H. pylori-positive nonulcer dyspepsia and
      low total antioxidant capacity. Patients in group A (n=80) were given
      lansoprazole (30 mg, BID), amoxicillin (1000 mg, BID), and clarithromycin (500
      mg, BID) for 14 days, as well as vitamin C (500 mg, BID) and vitamin E (200 IU,
      BID) for 30 days. Patients in group B (n=40) were given lansoprazole (30 mg,
      BID), amoxicillin (1000 mg, BID), and clarithromycin (500 mg, BID) for 14 days.
      RESULTS: Total antioxidant capacity were lower than normal levels in all
      patients. One hundred and fifteen patients (77 in group A, 38 in group B) were
      analyzed with per protocol analysis. In group A, H. pylori eradication was
      achieved in 63.8% of the patients included in the intention to treat analysis and
      in 66.2% of the patients included in the per protocol analysis. In group B, H.
      pylori eradication was achieved in 42.5% of the patients included in the
      intention to treat analysis and in 44.7% of the patients included in the per
      protocol analysis. Eradication rates were significantly higher in group A than in
      group B (P<0.005). CONCLUSIONS: Supplementation with vitamins C and E increased
      H. pylori eradication rate of standard triple therapy.

PMID- 21856268
TI  - Magnifying narrowband imaging is more accurate than conventional white-light
      imaging in diagnosis of gastric mucosal cancer.
AB  - BACKGROUND & AIMS: It is difficult to accurately diagnose patients with depressed
      gastric mucosal cancer based on conventional white-light imaging (C-WLI)
      endoscopy. We compared the real-time diagnostic yield of C-WLI for small,
      depressed gastric mucosal cancers with that of magnifying narrow-band imaging (M
      NBI). METHODS: We performed a multicenter, prospective, randomized, controlled
      trial of patients with undiagnosed depressed lesions <=10 mm in diameter
      identified by esophagogastroduodenoscopy. Patients were randomly assigned to
      groups that were analyzed by C-WLI (n = 176) or M-NBI (n = 177) immediately after
      detection; the C-WLI group received M-NBI after C-WLI. We compared the diagnostic
      accuracy, sensitivity, and specificity between C-WLI and M-NBI and assessed the
      diagnostic yield of M-NBI conducted in conjunction with C-WLI. RESULTS: Overall,
      40 gastric cancers (20 in each group) were identified. The median diagnostic
      values for M-NBI and C-WLI were as follows: accuracy, 90.4% and 64.8%;
      sensitivity, 60.0% and 40.0%; and specificity, 94.3% and 67.9%, respectively. The
      accuracy and specificity of M-NBI were greater than those of C-WLI (P < .001);
      the difference in sensitivity was not significant (P = .34). The combination of M
      NBI with C-WLI significantly enhanced performance compared with C-WLI alone;
      accuracy increased from (median) 64.8% to 96.6% (P < .001), sensitivity increased
      from 40.0% to 95.0% (P < .001), and specificity increased from 67.9% to 96.8% (P
      < .001). CONCLUSIONS: M-NBI, in conjunction with C-WLI, identifies small,
      depressed gastric mucosal cancers with 96.6% accuracy, 95.0% sensitivity, and
      96.8% specificity. These values are better than for C-WLI or M-NBI alone.

PMID- 21856269
TI  - Secondary, somatic mutations might promote cyst formation in patients with
      autosomal dominant polycystic liver disease.
AB  - BACKGROUND & AIMS: Heterozygous germline mutations in PRKCSH cause autosomal
      dominant polycystic liver disease (PCLD), but it is not clear how they lead to
      cyst formation. We investigated whether mutations in cyst epithelial cells and
      corresponding loss of the PRKCSH gene product (hepatocystin) contributed to cyst
      development. METHODS: Liver cyst material was collected through laparoscopic cyst
      fenestration from 8 patients with PCLD who had a heterozygous germline mutation
      in PRKCSH. Tissue sections from 71 cysts (2-14 per patient) were obtained for
      hepatocystin staining and mutation analysis. Cyst epithelium was acquired using
      laser microdissection; DNA was isolated and analyzed for loss of heterozygosity
      (LOH) and somatic mutations using restriction analysis and sequencing. Common
      single nucleotide polymorphisms (SNPs) in a 70-kilobase region surrounding the
      germline mutation were used to determine variations in the genomic region with
      LOH. RESULTS: The wild-type allele of PRKCSH was lost (LOH) in 76% of cysts
      (54/71). Hepatocystin was not detected in cyst epithelia with LOH, whereas
      heterozygous cysts still expressed hepatocystin. The variation observed in the
      LOH region analysis indicates that cysts develop independently. We also detected
      somatic mutations in PRKCSH in 17% (2/12) of the cysts without LOH. Trans
      heterozygous mutations in SEC63 were not observed. CONCLUSIONS: Among patients
      with PCLD who have a heterozygous germline mutation in PRKCSH, we found
      secondary, somatic mutations (second hits) in more than 76% of the liver cyst
      epithelia. PCLD is recessive at the cellular level, and loss of functional PRKCSH
      is an important step in cystogenesis.

PMID- 21856270
TI  - Brain-gut interactions increase peripheral nociceptive signaling in mice with
      postinfectious irritable bowel syndrome.
AB  - BACKGROUND & AIMS: To investigate the peripheral sensory effects of repeated
      stress in patients with postinfectious irritable bowel syndrome (IBS), we tested
      whether stress following self-limiting bacterial colitis increases colonic dorsal
      root ganglia (DRG) nociceptive signaling. METHODS: C57BL/6 mice were infected
      with Citrobacter rodentium. Stress was induced using a 9-day water avoidance
      paradigm (days 21-30 after infection). Colonic DRG neuronal excitability was
      measured using perforated patch clamp techniques, in vitro multi-unit afferent
      recordings, and measurements of visceromotor reflexes. RESULTS: Combined stress
      and prior infection increased corticosterone and epinephrine levels, compared
      with infected animals, but did not alter the resolution of colonic inflammation.
      These changes were associated with increased neuronal excitability and parallel
      changes in multi-unit afferent recordings and visceromotor reflex thresholds.
      Protease activity was increased at day 30 following infection with C rodentium.
      Protease inhibitors markedly reduced the effects of colonic supernatants on
      neuronal excitability from C rodentium but not stressed animals. Colonic DRG
      neurons expressed messenger RNAs for the beta(2) adrenergic and glucocorticoid
      receptors; incubation with stress mediators recapitulated the effects on neuronal
      excitability observed with chronic stress alone. PAR2 activation with
      concentrations of the activating peptide SLIGRL that had no effect on neuronal
      excitability in controls caused marked increases in excitability when applied to
      neurons from chronically stressed animals. CONCLUSIONS: Stress, combined with
      prior acute colitis, results in exaggerated peripheral nociceptive signaling.
      Proteases and stress mediators can signal directly to colonic DRG neurons;
      further analysis of these pathways could provide new targets for treatment of
      patients with postinfectious IBS.

PMID- 21856271
TI  - Autophagy and hepatic stellate cell activation - partners in crime?

PMID- 21856272
TI  - Nonviral transfection of leukemic primary cells and cells lines by siRNA-a direct
      comparison between Nucleofection and Accell delivery.
AB  - Transient downregulation of genes in vitro employing short interfering RNA
      (siRNA) is a time-honored approach to study gene function. A crucial prerequisite
      to obtain a downregulation is an efficient and nontoxic delivery of the siRNA
      into the target cells. However, this has proven difficult to accomplish,
      particular in cells in suspension. Thus, there is a need for a systematic
      evaluation of different methodologies to identify the most suitable protocol. We
      compared Nucleofection with Accell, a novel nonviral-based delivery system in the
      setting of leukemic blasts from patients with myeloid leukemias. Two cell surface
      proteins, human inhibitory C-type lectin-like receptor and CD96, both believed to
      be associated with leukemic stem cells, were chosen as target genes. Accell not
      only yielded higher transfection rates, but also retained superior cell
      viabilities for both cell lines and primary leukemic cells. Thus, transfection
      efficiencies in primary cells after Accell delivery was 85% (range, 71-97%)
      compared to 38% (23-65%) using Nucleofection for siRNA delivery. Preliminary
      studies of clonal growth of primary acute myeloid leukemia cells indicated growth
      inhibition after siRNA transfection. Our results reveal that Accell delivery is
      suitable for nonviral transfection of cells in suspension, including primary
      leukemic cells. These data should provide a platform for further studies of genes
      involved in early leukemogenesis.

PMID- 21856274
TI  - Implantable cardioverter-defibrillator shock reduction: the new paradigm.

PMID- 21856273
TI  - Impact of the hypomethylating agent 5-azacytidine on dendritic cells function.
AB  - Recent evidence suggested that 5-azacytidine (5-aza) can impact important immune
      functions via epigenetic modifications, making it an attractive candidate for
      pharmacologic manipulation of the immune system. The aim of this work was to
      study the effects of 5-aza on human dendritic cells (DC) generated from
      peripheral blood monocytes, and to test the type of immune response induced in
      patients treated with 5-aza. On the phenotypic level, CD40 and CD86 expression
      was significantly increased on mature DC exposed to 5-aza (5-aza-DC), compared
      with control untreated DC. Mature control DC and mature 5-aza-DC secreted
      comparable amounts of interleukin (IL)-6, IL-12p70, IL-23, and tumor necrosis
      factor-alpha. However, mature 5-aza-DC secreted significantly lower levels of IL
      10 and IL-27 compared to mature control DC (p = 0.04 and p = 0.005,
      respectively). In the peripheral blood of 14 patients (7 males and 7 females; age
      range, 53-81 years) with advanced myeloid malignancies (8 acute myeloid leukemia
      and 6 myelodysplastic syndrome) treated with 5-aza, there was a significant
      decrease of IL-4-secreting CD4(+) T cells (p = 0.001), and a significant increase
      of IL-17A- and IL-21-secreting CD4(+) T cells (p = 0.003 and p = 0.01,
      respectively, compared to 5 healthy donors) suggesting a Th17 response pattern in
      the blood of patients receiving 5-aza. In all, these data suggest potentially
      novel mechanisms of action of epigenetic therapies, such as 5-aza, which may have
      broader implications for immunotherapeutic strategies.

PMID- 21856275
TI  - Pharmacological treatment of atrial fibrillation: what does it take?

PMID- 21856276
TI  - Cell adhesion and focal contact formation on linear RGD molecular gradients:
      study of non-linear concentration dependence effects.
AB  - Cell adhesion onto bioengineered surfaces is affected by a number of variables,
      including the former substrate derivatization process. In this investigation, we
      studied the correlation between cell adhesion and cell-adhesive ligand surface
      concentration and organization due to substrate modification. For this purpose,
      Arg-Gly-Asp (RGD) gradient surfaces were created on poly(methyl methacrylate)
      substrates by continuous hydrolysis and were then grafted with biotin-PEG-RGD
      molecules. Cell culture showed that adhesion behavior changes in a nonlinear way
      in the narrow range of RGD surface densities assayed (2.8 to 4.4 pmol/cm(2)),
      with a threshold value of 4.0 pmol/cm(2) for successful cell attachment and
      spreading. This nonlinear dependence may be explained by nonhomogeneous RGD
      surface distribution at the nanometre scale, conditioned by the stochastic nature
      of the hydrolysis process. Atomic force microscopy analysis of the gradient
      surface showed an evolution of surface morphology compatible with this
      hypothesis. FROM THE CLINICAL EDITOR: The authors observed by AFM nonlinear
      dependence of cell adhesion on RGD gradient surfaces with different surface
      densities. The nonlinear characteristics may be explained by non-homogeneous RGD
      surface distribution at the nanometer scale, conditioned by the stochastic nature
      of the hydrolysis process.

PMID- 21856277
TI  - Characterization of metal-wear nanoparticles in pseudotumor following metal-on
      metal hip resurfacing.
AB  - Biopsies from a typical case of pseudotumor following metal-on-metal hip
      resurfacing (MoMHR) were analyzed using light and transmission electron
      microscopy, backscatter scanning electron microscopy and energy dispersive x-ray
      spectrometry (EDS). Heavy macrophage infiltration was observed in all black
      pigmented specimens. Metal nanoparticles (NPs) were observed exclusively within
      phagosomes of living macrophages and fragments of dead macrophages. Although dead
      fibroblasts were found to be juxtaposed with dead and disintegrated macrophages,
      the NPs were not seen within either live or dead fibroblasts. Chromium (Cr) but
      not cobalt (Co) was the predominant component of the remaining wear NPs in
      tissue. The current study finding suggests that corrosion of Co in phagosomes of
      macrophages and resultant Co ion release lead to tissue necrosis and adverse soft
      tissue reactions (pseudotumors). Further studies are required to elucidate the
      precise mechanism of intracellular corrosion of metal NPs and the long-term
      toxicity of the Cr remaining in the peri-prosthetic tissues. FROM THE CLINICAL
      EDITOR: In this study of metal-on-metal hip resurfacing-related tissue necrosis
      and pseudotumor formation, corrosion and decomposition of metallic cobalt in
      phagosomes of macrophages and resultant cobalt ion release were demonstrated to
      be the key elements of pathogenesis.

PMID- 21856278
TI  - The acidic domain of cytochrome c1 in paracoccus denitrificans, analogous to the
      acidic subunits in eukaryotic bc1 complexes, is not involved in the electron
      transfer reaction to its native substrate cytochrome c(552).
AB  - The cytochrome bc(1) complex is a key component in several respiratory pathways.
      One of the characteristics of the eukaryotic complex is the presence of a small
      acidic subunit, which is thought to guide the interaction of the complex with its
      electron acceptor and facilitate electron transfer. Paracoccus denitrificans
      represents the only example of a prokaryotic organism in which a highly acidic
      domain is covalently fused to the cytochrome c(1) subunit. In this work, a
      deletion variant lacking this acidic domain has been produced and purified by
      affinity chromatography. The complex is fully intact as shown by its X-ray
      structure, and is a dimer (Kleinschroth et al., subm.) compared to the tetrameric
      (dimer-of-dimer) state of the wild-type. The variant complex is studied by steady
      state kinetics and flash photolysis, showing wild type turnover and a virtually
      identical interaction with its substrate cytochrome c(552).

PMID- 21856280
TI  - Lung oxidative metabolism after exposure to ambient particles.
AB  - The aim of this work was to study the time course of the oxidative metabolism in
      mice lung after exposure to ambient particles (ROFA). Swiss mice were
      intranasally instilled with a ROFA suspension (0.20 mg/kg). Animals were
      sacrificed 1 or 3 h after the exposure. Eighty percentage of increased oxygen
      consumption was observed in tissue cubes after 1 h of exposure. This observation
      was accompanied by an increased NADPH oxidase activity (40%) and mitochondrial
      oxygen consumption in state 3 (19%). NO production by lung homogenates was found
      to be increased by 43% after 3 h of exposure. Phospholipid oxidation in lung
      homogenates showed a 29% increase after 1 h of exposure, while a 30% increase in
      the carbonyl content was found only after 3 h of exposure. Our data show the
      relative importance of different sources of reactive oxygen species (NADPH
      oxidase activity and mitochondrial respiration) to the increased tissue oxygen
      consumption, oxidative damage and antioxidant status observed in an acute model
      of ROFA particles exposure.

PMID- 21856281
TI  - The transcription factor Grainyhead like 3 (GRHL3) affects endothelial cell
      apoptosis and migration in a NO-dependent manner.
AB  - Migratory capacity and resistance to apoptosis are crucial for proper endothelial
      function. In a screen for anti-apoptotic genes in a breast cancer cell line, we
      identified Grainyhead like 3 (GRHL3). Therefore, the aim of our study was to
      investigate whether GRHL3 is expressed in endothelial cells and moreover, to
      determine its role in migration, apoptosis and senescence. GRHL3 is expressed in
      human endothelial cells. GRHL3 is required for endothelial cell migration. The
      underlying mechanism is independent of vascular endothelial growth factor. GRHL3
      induces Akt and endothelial nitric oxide synthase phosphorylation and its
      expression is increased by physiological concentrations of nitric oxide. Nitric
      oxide dependent migration is completely dependent on GRHL3 expression. Moreover,
      GRHL3 inhibits apoptosis of endothelial cells in an eNOS-dependent manner. Thus,
      loss of GRHL3 may result in endothelial dysfunction in vivo. One may consider new
      therapeutic strategies with the aim to conserve GRHL3 expression in the
      vasculature.

PMID- 21856282
TI  - Water transport in human aquaporin-4: molecular dynamics (MD) simulations.
AB  - Aquaporin-4 (AQP4) is the predominant water channel in the central nervous
      system, where it has been reported to be involved in many pathophysiological
      roles including water transport. In this paper, the AQP4 tetramer was modeled
      from its PDB structure file, embedded in a palmitoyl-oleoyl-phosphatidyl-choline
      (POPC) lipid bilayer, solvated in water, then minimized and equilibrated by means
      of molecular dynamics simulations. Analysis of the equilibrated structure showed
      that the central pore along the fourfold axis of the tetramers is formed with
      hydrophobic amino acid residues. In particular, Phe-195, Leu-191 and Leu-75, form
      the narrowest part of the pore. Therefore water molecules are not expected to
      transport through the central pore, which was confirmed by MD simulations. Each
      monomer of the AQP4 tetramers forms a channel whose walls consist mostly of
      hydrophilic residues. There are eight water molecules in single file observed in
      each of the four channels, transporting through the selectivity filter containing
      Arg-216, His-201, Phe-77, Ala-210, and the two conserved Asn-Pro-Ala (NPA) motifs
      containing Asn-213 and Asn-97. By using Brownian dynamics fluctuation-dissipation
      theorem (BD-FDT), the overall free-energy profile was obtained for water
      transporting through AQP4 for the first time, which gives a complete map of the
      entire channel of water permeation.

PMID- 21856279
TI  - The connexin43 carboxyl terminus and cardiac gap junction organization.
AB  - The precise spatial order of gap junctions at intercalated disks in adult
      ventricular myocardium is thought vital for maintaining cardiac synchrony.
      Breakdown or remodeling of this order is a hallmark of arrhythmic disease of the
      heart. The principal component of gap junction channels between ventricular
      cardiomyocytes is connexin43 (Cx43). Protein-protein interactions and
      modifications of the carboxyl-terminus of Cx43 are key determinants of gap
      junction function, size, distribution and organization during normal development
      and in disease processes. Here, we review data on the role of proteins
      interacting with the Cx43 carboxyl-terminus in the regulation of cardiac gap
      junction organization, with particular emphasis on Zonula Occludens-1. The rapid
      progress in this area suggests that in coming years we are likely to develop a
      fuller understanding of the molecular mechanisms causing pathologic remodeling of
      gap junctions. With these advances come the promise of novel approach to the
      treatment of arrhythmia and the prevention of sudden cardiac death. This article
      is part of a Special Issue entitled: The Communicating junctions, composition,
      structure and characteristics.

PMID- 21856283
TI  - REDD1 (regulated in development and DNA damage response 1) expression in skeletal
      muscle as a surrogate biomarker of the efficiency of glucocorticoid receptor
      blockade.
AB  - Glucocorticoids are potent regulators of cell metabolism, and in part act through
      a receptor-based mechanism to alter the transcription of target genes. A plethora
      of studies have utilized the glucocorticoid receptor antagonist, RU-486, both in
      vivo and in vitro, to reverse or prevent hormone-induced alterations in gene
      transcription. However, although RU-486 potently blocks many of the functions of
      the receptor, it does not lower plasma concentrations of the hormone, and a
      biomarker for the effectiveness of RU-486 in blocking receptor activation is
      lacking. In the present study, we demonstrate glucocorticoid-induced changes in
      expression of a protein referred to as regulated in development and DNA damage
      response (REDD1) in a variety of mouse models of hypercortisolemia including
      stroke, type 2 diabetes, and stress induced by confinement. Notably REDD1
      expression in skeletal muscle positively correlated with changes in
      corticosterone concentrations in all conditions. RU-486 had no effect on
      corticosterone concentrations, but strongly attenuated the stroke-, diabetes-,
      and stress-induced changes in REDD1 expression. Overall, the results of the
      present study suggest that changes in REDD1 expression in skeletal muscle
      represent an excellent surrogate biomarker for the efficacy of RU-486 treatment
      in repressing glucocorticoid action.

PMID- 21856284
TI  - Hepatic steatosis inhibits autophagic proteolysis via impairment of
      autophagosomal acidification and cathepsin expression.
AB  - Autophagy, one of protein degradation system, contributes to maintain cellular
      homeostasis and cell defense. Recently, some evidences indicated that autophagy
      and lipid metabolism are interrelated. Here, we demonstrate that hepatic
      steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is
      observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver
      from ob/ob mice more than control mice. Moreover, degradation of the long-lived
      protein leucine was significantly suppressed in hepatocytes isolated from ob/ob
      mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in
      hepatocytes from control mice; however, rate of LTR-stained autophagosomes in
      hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of
      autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice.
      Although fusion of isolated autophagosome and lysosome was not disturbed,
      proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L
      expression of liver were suppressed in ob/ob mice. These results indicate that
      lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal
      acidification and cathepsin expression.

PMID- 21856285
TI  - Kruppel-like factor-10 is directly regulated by carbohydrate response element
      binding protein in rat primary hepatocytes.
AB  - Kruppel-like factor (KLF)-10, is a circadian transcriptional regulator, which
      links the molecular clock to energy metabolism in the liver. Recently, it was
      reported that Klf-10 expression is induced by glucose stimulation in mouse
      hepatocytes. We previously reported that carbohydrate response element-binding
      protein (ChREBP) plays an important role in the regulation of hepatic lipogenic
      gene expression. Here, we investigate whether ChREBP, a glucose-activated
      transcription factor, directly regulates Klf-10 mRNA expression in rat primary
      hepatocytes. We found that both glucose stimulation and adenoviral overexpression
      of ChREBP induce Klf-10 mRNA expression in rat primary hepatocytes in a dose
      dependent manner. Conversely, overexpression of dominant-negative Max-like
      protein inhibits glucose-induction expression of Klf-10 mRNA. Deletion analysis
      using rat Klf-10 promoter in the pGL3 vector combined with a chromatin
      immunoprecipitation assay against the anti-ChREBP antibody demonstrated that the
      carbohydrate response element is located between -125 bp and -109 bp in the rat
      Klf-10 promoter. Conversely, adenoviral overexpression of KLF-10 partly inhibits
      glucose induction of ChREBP target genes in primary hepatocytes. In conclusion,
      these data suggest that crosstalk between ChREBP and KLF-10 is involved in the
      regulation of the lipogenic pathway.

PMID- 21856286
TI  - Direct evidence that RNA inhibits APOBEC3G ssDNA cytidine deaminase activity.
AB  - APOBEC3G (A3G) is a deoxycytidine deaminase active on ssDNA substrates. In HIV
      infected cells A3G interacted with reverse transcription complexes where its
      activity as a deoxycytidine deaminase led to mutation of the viral genome. A3G
      not only bound ssDNA, but it also had an intrinsic ability to bind RNA. In many
      cell types that can support HIV replication, A3G ssDNA deaminase activity was
      suppressed and the enzyme resided in high molecular mass, ribonucleoprotein
      complexes associated with cytoplasmic P-bodies and stress granules. Using a
      defined in vitro system, we show that RNA alone was sufficient to suppress A3G
      deaminase activity and did so in an RNA concentration-dependent manner. RNAs of
      diverse sequences and as short as 25nt were effective inhibitors. Native PAGE
      analyses showed that RNA formed ribonucleoprotein complexes with A3G and in so
      doing prevented ssDNA substrates from binding to A3G. The data provided direct
      evidence that A3G binding to cellular RNAs constituted a substantial impediment
      to the enzyme's ability to interact with ssDNA.

PMID- 21856287
TI  - Blocking peptides against HBV: preS1 protein selected from a phage display
      library.
AB  - The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV)
      surface and has been shown to have a pivotal function in viral infectivity and
      assembly. The development of reagents with high affinity and specificity for
      PreS1 is of great significance for early diagnosis and treatment of HBV
      infection. A phage display library of dodecapeptide was screened for interactions
      with purified PreS1 protein. Alignment of the positive phage clones revealed a
      putative consensus PreS1 binding motif of HX(n)HX(m)HP/R. Moreover, a peptide
      named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high
      frequency of 72%. A thermodynamic study revealed that P7 has a higher binding
      affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate
      the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key
      functional sites on the native PreS1 protein. This newly isolated peptide may,
      therefore, be a new therapeutic candidate for the treatment of HBV. The consensus
      motif could be modified to deliver imaging, diagnostic, and therapeutic agents to
      tissues affected by HBV.

PMID- 21856289
TI  - DAX1 suppresses FXR transactivity as a novel co-repressor.
AB  - Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile
      acid, glucose and lipid homeostasis through regulation of numerous genes involved
      in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage
      sensitive sex reversal adrenal hypoplasia congenital critical region on X
      chromosome, gene 1) is an atypical member of the nuclear receptor family due to
      lack of classical DNA-binding domains and acts primarily as a co-repressor of
      many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR
      in the nucleus and acted as a negative regulator of FXR through a physical
      interaction with FXR. Our study showed that over-expression of DAX1 down
      regulated the expression of FXR target genes, whereas knockdown of DAX1 led to
      their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1
      were required for the full repression of FXR transactivation. In addition, our
      study characterized that DAX1 suppresses FXR transactivation via competing with
      co-activators such as SRC-1 and PGC-1alpha. In conclusion, DAX1 acts as a co
      repressor to negatively modulate FXR transactivity.

PMID- 21856288
TI  - Alternative splicing of T-box transcription factor genes.
AB  - T-box (TBX) transcription factors are an ancient gene family with critical roles
      in embryogenesis. Currently, TBX3, TBX5, and TBX20 are TBX genes defined to have
      multiple protein isoforms created by alternative splicing and characterized by
      expression and functional studies. These proteins are important for development
      as mutations lead to severe developmental disorders in humans and mice.
      Cumulative studies suggest that alternative splicing of these genes can regulate
      TBX activities during multiple biological processes including cardiogenesis, limb
      development, and cancer mechanisms. This mini-review focuses on how alternative
      splicing adds complexity to transcriptional regulation of target genes controlled
      by TBX transcription factors.

PMID- 21856290
TI  - Acidosis leads to neurological disorders through overexciting cortical pyramidal
      neurons.
AB  - The patients suffering from acidosis usually sign psychological deficits. The
      cerebral dysfunction is reportedly caused by an acid-induced functional
      impairment of GABAergic neurons; however, the role of pyramidal neurons in this
      process remains unclear. By using electrophysiological method and changing
      extracellular pH, we investigated the influence of acidic environment on
      pyramidal neurons in the cortical slices, such as their ability of firing spikes
      and response to synaptic inputs. A low pH of artificial cerebral spinal fluid
      elevates the responses of pyramidal neurons to excitatory synaptic inputs and
      their ability of encoding digital spikes, as well as reduces the signal
      transmission at GABAergic synapses. The elevated ability of neuronal spiking is
      associated with the decreases of refractory periods and threshold potentials.
      Therefore, acidosis deteriorates brain functions through making the activities
      between cortical pyramidal neurons and GABAergic neurons imbalanced toward the
      overexcitation of neural networks, a process similar to neural excitotoxicity.

PMID- 21856291
TI  - Human arylacetamide deacetylase is responsible for deacetylation of rifamycins:
      rifampicin, rifabutin, and rifapentine.
AB  - Rifamycins such as rifampicin, rifabutin, and rifapentine are used for the
      treatment of tuberculosis and induce various drug-metabolizing enzymes.
      Rifamycins have been reported to be mainly deacetylated by esterase(s) expressed
      in human liver microsomes (HLM) to 25-deacetylrifamycins, but the responsible
      enzyme remained to be determined. In this study, we found that recombinant human
      arylacetamide deacetylase (AADAC) could efficiently deacetylate rifamycins,
      whereas human carboxylesterases, which are enzymes responsible for the hydrolysis
      of many prodrugs, showed no activity. The involvement of AADAC in the
      deacetylation of rifamycins in HLM was verified by the similarities of the K(m)
      and K(i) values and the inhibitory characteristics between recombinant AADAC and
      HLM. Rifamycins exhibited potent cytotoxicity to HepG2 cells, but their 25
      deacetylated metabolites did not. Luciferase assay using a reporter plasmid
      containing CYP3A4 direct repeat 3 and everted repeat 6 motifs revealed that 25
      deacetylrifamycins have lesser potency to transactivate CYP3A4 compared with the
      parent drugs. Supporting these results, HepG2 cells infected with a recombinant
      adenovirus expressing human AADAC showed low cytotoxicity and induction potency
      of CYP3A4 by rifamycins. In addition, CYP3A4 induction in human hepatocytes by
      rifamycins was increased by transfecting siRNA for human AADAC. Thus, we found
      that human AADAC was the enzyme responsible for the deacetylation of rifamycins
      and would affect the induction rate of drug-metabolizing enzymes by rifamycins
      and their induced hepatotoxicity.

PMID- 21856293
TI  - Characterizing the effect of UDP-glucuronosyltransferase (UGT) 2B7 and UGT1A9
      genetic polymorphisms on enantioselective glucuronidation of flurbiprofen.
AB  - Flurbiprofen (FPF), available commercially as a racemic mixture, is a propionic
      acid derivative of non-steroidal anti-inflammatory drugs (NSAIDs) with known
      stereoselective glucuronidation. The major enzyme catalyzing this conjugation
      reaction is UDP-glucuronosyltransferase (UGT) 2B7, with minor contributions by
      UGT1A9. This study examines the role of the genetic variants of UGT2B7 and 1A9
      enzymes involved in the formation of acyl glucuronides (FPFGs). Variants caused
      by three single nucleotide polymorphisms (SNPs) (A71S, 211G>T; H268Y, 802C>T; and
      D398N, 1192G>A) in UGT2B7 and three SNPs (C3Y, 8G>A; M33T, 98T>C; D256N, 766G>A)
      in UGT1A9 showed activity changes toward different substrates. However the
      functional impacts of these SNPs on chiral substrates were not examined. Upon
      stable expression in Bac-to-Bac system, UGT2B7*71S (A(71)S), UGT2B7*2 (H(268)Y)
      and UGT2B7*5 (D(398)N) were all associated with a decrease in the formation of
      FPFGs. Compared with UGT2B7*1 (wild-type), UGT2B7*71S exhibited a >2-fold lower
      intrinsic clearance mainly by altered capacities (V(max)). Furthermore, a >14
      fold decreased intrinsic clearance of the *1 protein was produced by UGT2B7*2 and
      UGT2B7*5. However, no significantly stereoselective difference for the formation
      of (R)- and (S)-FPFG was found among these UGT2B7 allozymes. UGT1A9*2 (C(3)Y)
      exhibited a higher V(max) (3.2-fold), K(m) (2.1-fold) and intrinsic clearance
      (1.6-fold) toward (S)-FPF than UGT1A9*1 (wild-type). UGT1A9*3 (M(33)T) almost
      lost the catalytic activity to FPF. A significantly stereoselective difference on
      the glucuronidation of rac-FPF was seen between the two variants compared with
      the wild type of UGT1A9.

PMID- 21856292
TI  - The flavonoid quercetin in disease prevention and therapy: facts and fancies.
AB  - Biochemical and genetic studies on cellular and animal models on the mechanism(s)
      of action of phytochemicals provide a functional explanation of how and why a
      diet rich in fruits and vegetables is considered healthy. It is not unusual to
      find molecules that protect against diseases, which greatly differ from a
      physiopathological point of view, such as cancer and cardiovascular disorders.
      Quercetin falls into this category and possesses a broad range of biological
      properties. Uptake, metabolism and circulating concentrations of quercetin and
      its metabolites suggest that a regular diet provides amounts of quercetin (<1
      MUM) not compatible with its chemopreventive and/or cardioprotective effects.
      However, it appears relatively easy to increase total quercetin concentrations in
      plasma (>10 MUM) by supplementation with quercetin-enriched foods or supplements.
      Multiple lines of experimental evidence suggest a positive association between
      quercetin intake and improved outcomes of inflammatory cardiovascular risk. The
      ameliorating effect of quercetin administration can be extended to other chronic
      inflammatory disorders but only if supplementation occurs in patients. Quercetin
      can be considered the prototype of a naturally-occurring chemopreventive agent
      because of its key roles in triggering the "hallmarks of cancer". However,
      several critical points must be taken into account when considering the potential
      therapeutic use of this molecule: (1) pharmacological versus nutraceutical doses
      applied, (2) specificity of its mechanism of action compared to other
      phytochemicals, and (3) identification of "direct" cellular targets. The design
      of specific clinical trials is extremely warranted to depict possible
      applications of quercetin in adjuvant cancer therapy.

PMID- 21856294
TI  - 15-Hydroxyprostaglandin dehydrogenase as a novel molecular target for cancer
      chemoprevention and therapy.
AB  - Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in arachidonic acid cascade,
      plays a key role in the biosynthesis of prostaglandin E(2) (PGE(2)) upon
      inflammatory insults. Overproduction of PGE(2) stimulates proliferation of
      various cancer cells, confers resistance to apoptosis of cancerous or transformed
      cells, and accelerates metastasis and angiogenesis. Excess PGE(2) undergoes
      metabolic inactivation which is catalyzed by NAD(+)-dependent 15
      hydroxyprostaglandin dehydrogenase (15-PGDH). In this context, 15-PGDH has been
      speculated as a physiological antagonist of COX-2 and a tumor suppressor. Thus,
      overexpression of 15-PGDH has been known to protect against experimentally
      induced carcinogenesis and renders the cancerous or transformed cells susceptible
      to apoptosis by counteracting oncogenic action of PGE(2). In contrast, silence of
      15-PGDH is observed in some cancer cells, which is associated with epigenetic
      modification, such as DNA methylation and histone deacetylation, in the promoter
      region of 15-PGDH. A variety of compounds capable of inducing the expression of
      15-PGDH have been reported, which include the histone deacetylase inhibitors,
      nonsteroidal anti-inflammatory drugs, and peroxisome proliferator-activated
      receptor-gamma agonists. Therefore, 15-PGDH may be considered as a novel
      molecular target for cancer chemoprevention and therapy. This review highlights
      the role of 15-PGDH in carcinogenesis and its regulation.

PMID- 21856295
TI  - Effects of cooling and freezing on the motility of Ostrea edulis (L., 1758)
      spermatozoa after thawing.
AB  - The aim of this work was to evaluate the effects of temperature, cryoprotectant
      agents and freezing curves on sperm motility of Ostrea edulis. All phases of
      cryopreservation were studied (evaluation of semen motility pattern, choice of
      cryoprotectants and freezing rates) to restore after thawing the motility
      characteristics distinctive of fresh semen. To assess the temperature effects on
      sperm motility, semen was activated using four different temperatures (25, 18, 10
      and 3 degrees C). Sperm aliquots were maintained inactive at these temperatures
      for 1 and 3h, then activated with FSW at same temperature of conservation. Sperm
      was activated and incubated to 3 degrees C with dimethylsulfoxide (Me(2)SO),
      ethylene glycol (EG), 1-2 propylene glycol (PG) (5%, 7%, 10% and 15% final
      concentrations), glycerol (GlOH; 5%, 10% and 15% final concentrations) and
      methanol (MetOH; 4% and 10% final concentrations) for 10, 20 and 30min. A first
      evaluation of freezing rates was made by testing four freezing curves: -1, -3, -6
      and -10 degrees C/min. Then, an optimization was made by testing four freezing
      curves: -2.5, -3.0, -3.5 and -4 degrees C/min. The selected temperature for short
      term conservation has been 3 degrees C, because only this temperature has allowed
      good sperm motility conservation after 3h of dry-storage; this is a time
      sufficient to conduct cryopreservation procedures. The sperm showed a particular
      sensitivity to GlOH and PG to all tested concentrations and to 15% Me(2)SO. EG
      and MetOH to all concentrations and Me(2)SO to concentrations lower than 15% have
      not shown significant toxic effects. The freezing rate -3 degrees C/min using 15%
      EG has shown an highest percentage of RVF (rapid, vigorous and forward)
      spermatozoa (class 3, about 75% of fresh semen) and an highest sperm motility
      duration.

PMID- 21856296
TI  - Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell
      development and endocrine hormone expression.
AB  - Nkx2.2 and Arx are essential pancreatic transcription factors. Nkx2.2 is
      necessary for the appropriate specification of the islet alpha, beta, PP and
      epsilon cell lineages, whereas Arx is required to form the correct ratio of
      alpha, beta, delta and PP cells. To begin to understand the cooperative functions
      of Nkx2.2 and Arx in the development of endocrine cell lineages, we generated
      progenitor cell-specific deletions of Arx on the Nkx2.2 null background. The
      analysis of these mutants demonstrates that expansion of the ghrelin cell
      population in the Nkx2.2 null pancreas is not dependent on Arx; however, Arx is
      necessary for the upregulation of ghrelin mRNA levels in Nkx2.2 mutant epsilon
      cells. Alternatively, in the absence of Arx, delta cell numbers are increased and
      Nkx2.2 becomes essential for the repression of somatostatin gene expression.
      Interestingly, the dysregulation of ghrelin and somatostatin expression in the
      Nkx2.2/Arx compound mutant (Nkx2.2(null);Arx(Deltapanc)) results in the
      appearance of ghrelin+/somatostatin+ co-expressing cells. These compound mutants
      also revealed a genetic interaction between Nkx2.2 and Arx in the regulation of
      the PP cell lineage; the PP cell population is reduced when Nkx2.2 is deleted but
      is restored back to wildtype numbers in the Nkx2.2(null);Arx(Deltapanc) mutant.
      Moreover, conditional deletion of Arx in specific pancreatic cell populations
      established that the functions of Arx are necessary in the Neurog3+ endocrine
      progenitors. Together, these experiments identify novel genetic interactions
      between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the
      correct specification and regulation of endocrine hormone-producing cells.

PMID- 21856297
TI  - Intestinal stem cells in the adult Drosophila midgut.
AB  - Drosophila has long been an excellent model organism for studying stem cell
      biology. Notably, studies of Drosophila's germline stem cells have been
      instrumental in developing the stem cell niche concept. The recent discovery of
      somatic stem cells in adult Drosophila, particularly the intestinal stem cells
      (ISCs) of the midgut, has established Drosophila as an exciting model to study
      stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the
      major signaling pathways that regulate the self-renewal, proliferation and
      differentiation of Drosophila ISCs, discussing how this regulation maintains
      midgut homeostasis and mediates regeneration of the intestinal epithelium after
      injury.

PMID- 21856298
TI  - Schistosoma japonicum: treatment of different developmental stages in mice with
      long-acting praziquantel implants.
AB  - This paper reports the effective treatment of Schistosoma japonicum in a mouse
      model with long-acting praziquantel (PZQ)-loaded poly(epsilon-caprolactone)
      implants. The implants yielded stable, high plasma PZQ concentrations ranging 100
      1600 ng/mL during the 40-day investigation period. For assessment of efficacy,
      the implants were implanted into mice immediately after infection and at 1, 2, 3
      and 4 weeks after infection to treat the schistosomes at different developmental
      stages. All the mice were sacrificed at 6 weeks after infection for worm and egg
      recovery, worm morphology examination, and histopathological analysis of
      implantation site tissues. The worm burdens, egg burdens, and numbers of
      miracidia hatched from the retrieved eggs for all the implant-treated groups
      (except groups T2-A, T4 and T5) were reduced by 100% when compared with the
      control group. From groups T2-A, T4 and T5, some schistosome debris was
      recovered. Eggs were found in only group T5 for which the time between infection
      and implantation was 4 weeks, which enabled the maturation of juvenile female
      schistosomes into adult ones that lay eggs. Histopathological observations of
      implantation tissue showed no evidence of granulomatous foreign-body or lymphoid
      cell aggregation, demonstrating good biocompatibility of the PZQ implants. These
      results demonstrate that the long-acting PZQ implants can kill schistosomes at
      any developmental stages and attenuate/avoid the associated liver damage.

PMID- 21856300
TI  - Free sphingobases induce RBOHD-dependent reactive oxygen species production in
      Arabidopsis leaves.
AB  - Sphingolipids are implied in several regulatory processes, including cell death.
      Levels of the free sphingobase t18:0 (phytosphingosine) increase in Arabidopsis
      in response to the bacterial pathogen Pseudomonas syringae. To gain information
      on sphingobase-induced signaling, we determined kinetics of leaf reactive oxygen
      species (ROS) levels and cell death in response to specific sphingobases. t18:0,
      d18:0 and d17:1, but not d20:0, induced ROS and cell death within 1.5-2h. Early
      sphingobase-induced ROS production was independent of cell death induction and
      required the NADPH oxidase Respiratory Burst Oxidase Homolog D (RBOHD). Specific
      sphingobases can therefore induce cell death and require RBOHD for early ROS
      induction in plants.

PMID- 21856299
TI  - The role of intramolecular interactions in the functional control of multiheme
      cytochromes c.
AB  - Detailed thermodynamic and structural data measured in soluble monomeric
      multiheme cytochromes c provided the basis to investigate the functional
      significance of interactions between redox co-factors. The steep decay of
      intramolecular interactions with distance means that close proximity of the redox
      centers is necessary to modulate the intrinsic reduction potentials in a
      significant way. This ensures selection of specific populations during redox
      activity in addition to maintaining fast intramolecular electron transfer.
      Therefore, intramolecular interactions between redox co-factors play an important
      role in establishing the biological function of the protein by controlling how
      electrons flow through and are distributed among the co-factors.

PMID- 21856301
TI  - Characterization of benzoxaborole-based antifungal resistance mutations
      demonstrates that editing depends on electrostatic stabilization of the leucyl
      tRNA synthetase editing cap.
AB  - The broad-spectrum benzoxaborole antifungal AN2690 blocks protein synthesis by
      inhibiting leucyl-tRNA synthetase (LeuRS) via a novel oxaborole tRNA trapping
      mechanism in the editing site. Herein, one set of resistance mutations is at
      Asp487 outside the LeuRS hydrolytic editing pocket, in a region of unknown
      function. It is located within a eukaryote/archaea specific insert I4, which
      forms part of a cap over a benzoxaborole-AMP that is bound in the LeuRS CP1
      domain editing active site. Mutational and biochemical analysis at Asp487
      identified a salt bridge between Asp487 and Arg316 in the hinge region of the I4
      cap of yeast LeuRS that is critical for tRNA deacylation. We hypothesize that
      this electrostatic interaction stabilizes the cap during binding of the editing
      substrate for hydrolysis.

PMID- 21856302
TI  - The Y641C mutation of EZH2 alters substrate specificity for histone H3 lysine 27
      methylation states.
AB  - Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of
      EZH2 have been identified in patients with certain subtypes of non-Hodgkin
      lymphoma (NHL). These mutations were shown to change the substrate specificity of
      EZH2 for various methylation states of lysine 27 on histone H3 (H3K27). An
      additional mutation at EZH2 Y641 to cysteine (Y641C) was also found in one
      patient with NHL and in SKM-1 cells derived from a patient with myelodisplastic
      syndrome (MDS). The Y641C mutation has been reported to dramatically reduce
      enzymatic activity. Here, we demonstrate that while the Y641C mutation ablates
      enzymatic activity against unmethylated and monomethylated H3K27, it is superior
      to wild-type in catalyzing the formation of trimethylated H3K27 from the
      dimethylated precursor.

PMID- 21856303
TI  - Protein oligomerization mediated by the transmembrane carboxyl terminal domain of
      Bcl-XL.
AB  - Bcl-XL is a pro-survival member of the Bcl-2 family that can be found in the
      outer mitochondrial membrane and in soluble cytosolic homodimers. Bcl-XL can bind
      pro-apoptotic members of this family preventing them from activating the
      execution phase of apoptosis. Bcl-XL has been shown to homodimerize in different
      ways, although most binding and structural assays have been carried out in the
      absence of its carboxyl terminal transmembrane domain. We show here that this
      domain can by itself direct protein oligomerization, which could be related to
      its previously reported role in mitochondrial morphology alterations and
      apoptosis inhibition.

PMID- 21856304
TI  - A rare cause of obscure gastrointestinal bleeding. Diagnosis: Sporadic Peutz
      Jeghers type jejunal polyp causing obsucre GI bleeding.

PMID- 21856305
TI  - Matrix metalloproteinase-12 leads to elastin degradation in BALB/c mice with
      eosinophilic meningitis caused by Angiostrongylus cantonensis.
AB  - The rat lugworm Angiostrongylus cantonensis can cause eosinophilic meningitis.
      The purpose of this study was to determine whether matrix metalloproteinase (MMP)
      12 and its substrate elastin participate in this inflammatory response. We showed
      that the MMP-12/tissue inhibitor of metalloproteinase-1 ratio was significantly
      increased in the CSF of A. cantonensis-infected mice from day 10 p.i., and
      reached high levels on days 20 and 25 p.i. MMP-12 production was correlated with
      elastin degradation, eosinophil count, blood-CSF barrier permeability and
      pathological changes in the subarachnoid space. Also, MMP-12 might contribute to
      elastin degradation in the meningeal vessel of the subarachnoid space.
      Simultaneous administration of albendazole and doxycycline significantly reduced
      the levels of MMP-12, elastin and Evans blue in mice with meningitis. These
      results imply that MMP-12 contributes to the elastin degradation that occurs in
      angiostrongyliasis meningitis, and doxycycline can reverse related inflammatory
      events by inhibition of MMP-12.

PMID- 21856307
TI  - RNA interference of beta1 integrin subunit impairs development and immune
      responses of the beet armyworm, Spodoptera exigua.
AB  - Integrin is a cell surface protein that is composed of alpha and beta heterodimer
      and mediates cell interaction with extracellular matrix or other cells including
      microbial pathogens. A full length cDNA sequence (2862 bp) of a beta1 subunit
      integrin (betaSe1) was cloned from the beet armyworm, Spodoptera exigua.
      Phylogenetic analysis showed that betaSe1 was clustered with other insect beta
      integrin subunits with the highest amino acid sequence identity (98.3%) to beta1
      of Spodoptera litura. Structural analysis of the deduced amino acid sequence
      indicated that betaSe1 possessed all functional domains known in other insect
      beta1 integrins. RT-PCR analysis showed that betaSe1 was expressed in all
      developmental stages and all tested tissues of S. exigua. Its expression was
      further upregulated in hemocytes by injections of various microbes from
      quantitative RT-PCR analysis. Injection of double-stranded betaSe1 RNA
      (dsRNA(betaSe1)) into late instar S. exigua suppressed betaSe1 expression and
      resulted in significant reduction in pupal weight. The dsRNA(betaSe1) injection
      significantly impaired hemocyte-spreading and nodule formation of S. exigua in
      response to bacterial challenge. Furthermore, oral ingestion of dsRNA(betaSe1)
      induced reduction of betaSe1 expression in midgut and resulted in significant
      mortality of S. exigua during immature development. These results suggest that
      betaSe1 plays crucial roles in performing cellular immune responses as well as
      larval development in S. exigua.

PMID- 21856306
TI  - Comparison of the efficiency of antibody selection from semi-synthetic scFv and
      non-immune Fab phage display libraries against protein targets for rapid
      development of diagnostic immunoassays.
AB  - Rapid development of diagnostic immunoassays against novel emerging or
      genetically modified pathogens in an emergency situation is dependent on the
      timely isolation of specific antibodies. Non-immune antibody phage display
      libraries are an efficient in vitro method for selecting monoclonal antibodies
      and hence ideal in these circumstances. Such libraries can be constructed from a
      variety of sources e.g. B cell cDNA or synthetically generated, and use a variety
      of antibody formats, typically scFv or Fab. However, antibody source and format
      can impact on the quality of antibodies generated and hence the effectiveness of
      this methodology for the timely production of antibodies. We have carried out a
      comparative screening of two antibody libraries, a semi-synthetic scFv library
      and a human-derived Fab library against the protective antigen toxin component of
      Bacillus anthracis and the epsilon toxin of Clostridium botulinum. We have shown
      that while the synthetic library produced a diverse collection of specific scFv
      phage, these contained a high frequency of unnatural amber stops and
      glycosylation sites which limited their conversion to IgG, and also a high number
      which lost specificity when expressed as IgG. In contrast, these limitations were
      overcome by the use of a natural human library. Antibodies from both libraries
      could be used to develop sandwich ELISA assays with similar sensitivity. However,
      the ease and speed with which full-length IgG could be generated from the human
      derived Fab library makes screening this type of library the preferable method
      for rapid antibody generation for diagnostic assay development.

PMID- 21856308
TI  - Differential control of light-dark adaptation in the ocelli and compound eyes of
      Triatoma infestans.
AB  - The adaptation to light of compound eyes in insects has been extensively
      documented and their adaptive role is well understood. Much less attention has
      been paid, however, to the control of ocelli sensitivity, a study which could
      help us to understand the functional role of these simple eyes. We analyzed the
      dynamic changes in the distribution of screening pigments which occur in the
      ocelli of the haematophagous bug, Triatoma infestans, when the insects are
      subjected either to light/dark cycles (LD), to constant darkness (DD) or constant
      light (LL). We then compared these changes with those occurring in the compound
      eyes of the same individuals and found that, while compound eyes are subject to
      the control of an endogenous circadian clock, the adaptation of the ocelli is
      entirely dependent on environmental illumination. In addition, we have observed
      that environmental temperature is not involved in the control of screening
      pigments in either ocelli or compound eyes as a direct stimulus, nor as a
      Zeitgeber. The existence of a differential control in the components of the dual
      visual system represents an adaptive advantage in the adjustment of visual
      sensitivity in insects exposed to quick changes in lighting conditions in their
      natural habitat. We discuss the implications of our findings with regards to the
      biology of triatomines and with respect to the general understanding the
      functional role of insect ocelli.

PMID- 21856309
TI  - Margolisiella islandica sp. nov. (Apicomplexa: Eimeridae) infecting Iceland
      scallop Chlamys islandica (Muller, 1776) in Icelandic waters.
AB  - Wild Iceland scallops Chlamys islandica from an Icelandic bay were examined for
      parasites. Queen scallops Aequipecten opercularis from the Faroe Islands and king
      scallops Pecten maximus and queen scallops from Scottish waters were also
      examined. Observations revealed heavy infections of eimeriorine parasites in 95
      100% of C. islandica but not the other scallop species. All life stages in the
      apicomplexan reproduction phases, i.e. merogony, gametogony and sporogony, were
      present. Trophozoites and meronts were common within endothelial cells of the
      heart's auricle and two generations of free merozoites were frequently seen in
      great numbers in the haemolymph. Gamonts at various developmental stages were
      also abundant, most frequently free in the haemolymph. Macrogamonts were much
      more numerous than microgamonts. Oocysts were exclusively in the haemolymph; live
      mature oocysts contained numerous (>500) densely packed pairs of sporozoites
      forming sporocysts. Analysis of the 18S ribosomal DNA revealed that the parasite
      from C. islandica is most similar (97.7% identity) to an unidentified
      apicomplexan isolated from the haemolymph of the giant clam, Tridacna crocea,
      from Japan. Phylogenetic analyses showed that the novel sequence consistently
      grouped with the Tridacna sequence which formed a robust sister clade to the
      rhytidocystid group. We propose the name Margolisiella islandica sp. nov.,
      referring to both type host and type locality.

PMID- 21856310
TI  - Spiny-cheek crayfish Orconectes limosus carry a novel genotype of the crayfish
      plague pathogen Aphanomyces astaci.
AB  - The oomycete Aphanomyces astaci causes mass mortalities of European crayfish.
      Different species of North American crayfish, original hosts of this parasite,
      seem to carry different strains of A. astaci. So far, four distinct genotype
      groups have been recognised using Random Amplification of Polymorphic DNA (RAPD
      PCR). We succeeded in isolating A. astaci from the spiny-cheek crayfish
      Orconectes limosus, a widespread invader in Europe, and confirmed that this
      species carries a novel A. astaci genotype. Improving knowledge on the diversity
      of this parasite may facilitate identification of genotypes in mass mortalities
      of European crayfish, thus tracing the sources of infection.

PMID- 21856311
TI  - HuCAL PLATINUM, a synthetic Fab library optimized for sequence diversity and
      superior performance in mammalian expression systems.
AB  - This article describes the design of HuCAL (human combinatorial antibody library)
      PLATINUM, an optimized, second-generation, synthetic human Fab antibody library
      with six trinucleotide-randomized complementarity-determining regions (CDRs).
      Major improvements regarding the optimized antibody library sequence space were
      implemented. Sequence space optimization is considered a multistep process that
      includes the analysis of unproductive antibody sequences in order to, for
      example, avoid motifs such as potential N-glycosylation sites, which are
      undesirable in antibody production. Gene optimization has been used to improve
      expression of the antibody master genes in the library context. As a result, full
      length IgGs derived from the library show both significant improvements in
      expression levels and less undesirable glycosylation sites when compared to the
      previous HuCAL GOLD library. Additionally, in-depth analysis of sequences from
      public databases revealed that diversity of CDR-H3 is a function of loop length.
      Based upon this analysis, the relatively uniform diversification strategy used in
      the CDR-H3s of the previous HuCAL libraries was changed to a length-dependent
      design, which replicates the natural amino acid distribution of CDR-H3 in the
      human repertoire. In a side-by-side comparison of HuCAL GOLD and HuCAL PLATINUM,
      the new library concept led to isolation of about fourfold more unique sequences
      and to a higher number of high-affinity antibodies. In the majority of HuCAL
      PLATINUM projects, 100-300 antibodies each having different CDR-H3s are obtained
      against each antigen. This increased diversity pool has been shown to
      significantly benefit functional antibody profiling and screening for superior
      biophysical properties.

PMID- 21856312
TI  - Water molecules in the nucleotide binding cleft of actin: effects on subunit
      conformation and implications for ATP hydrolysis.
AB  - In the monomeric actin crystal structure, the positions of a highly organized
      network of waters are clearly visible within the active site. However, the
      recently proposed models of filamentous actin (F-actin) did not extend to
      including these waters. Since the water network is important for ATP hydrolysis,
      information about water position is critical to understanding the increased rate
      of catalysis upon filament formation. Here, we show that waters in the active
      site are essential for intersubdomain rotational flexibility and that they
      organize the active-site structure. Including the crystal structure waters during
      simulation setup allows us to observe distinct changes in the active-site
      structure upon the flattening of the actin subunit, as proposed in the Oda model
      for F-actin. We identify changes in both protein position and water position
      relative to the phosphate tail that suggest a mechanism for accelerating the rate
      of nucleotide hydrolysis in F-actin by stabilizing charge on the beta-phosphate
      and by facilitating deprotonation of catalytic water.

PMID- 21856313
TI  - Age-specific mortality risk from pandemic influenza.
AB  - Younger age groups account for proportionally more mortality in influenza
      pandemics than in seasonal influenza epidemics. Mechanisms that might explain
      this include young people suffering from an over-reactive immune system
      ("cytokine storm"), older people benefiting from cross-immunity from a wider
      variety of previous influenza infections ("antigenic history"), and lifetime
      immune responses in all people being shaped by their first influenza A infection
      ("antigenic imprinting" or "original antigenic sin"). We examined whether these
      mechanisms can explain age-specific influenza mortality patterns, using the
      complete database of individual deaths in Canada from 1951 to 1999. The mortality
      pattern during the 1957 pandemic indicates that antigenic imprinting plays an
      important role in determining age-specific influenza virulence and that both
      shift years and major drift years contribute significantly to antigenic imprints.
      This information should help pandemic planners to identify age groups that might
      respond differently to novel influenza strains.

PMID- 21856314
TI  - Comparative aneugenicity of doxorubicin and its derivative idarubicin using
      fluorescence in situ hybridization techniques.
AB  - The present study was designed to evaluate and compare the aneugenicity of
      idarubicin and doxorubicin, topoisomerase-targeting anticancer anthracyclines,
      using fluorescence in situ hybridization techniques. It was found that idarubicin
      and doxorubicin treatment (12 mg/kg) induced sperm meiotic delay of 24h. To
      determine the frequencies of disomic and diploid sperm, groups of 5 male Swiss
      albino mice were treated with 3, 6 and 12 mg/kg idarubicin or doxorubicin.
      Significant increases in the frequencies of disomic and diploid sperm were caused
      by treatment with all doses of idarubicin and the two highest doses of
      doxorubicin compared with the controls. Moreover, both compounds significantly
      increased the frequency of diploid sperm, indicating that complete meiotic arrest
      occurred. The observation that XX- and YY-sperm significantly prevailed XY-sperm
      indicates missegregation during the second meiotic division. The results suggest
      also that earlier prophase stages contribute relatively less to idarubicin and
      doxorubicin-induced aneuploidy. Effects of the same doses were investigated by
      the bone-marrow micronucleus test. Significant increases in the frequencies of
      micronuclei were found after treatment with all doses of both compounds. The
      responses were also directly correlated with bone marrow suppression. Idarubicin
      was more toxic than doxorubicin. Exposure to 12 mg/kg of idarubicin and
      doxorubicin yielded 3.82 and 2.64% micronuclei, respectively, and of these an
      average of 58.3 and 62.8%, respectively, showed centromeric signals, indicating
      their formation by whole chromosomes and reflecting the aneugenic activity of
      both compounds. Correspondingly, about 41.7 and 37.2% of the induced micronuclei,
      respectively, were centromere-negative, demonstrating that both compounds not
      only induce chromosome loss but also DNA strand breaks. Based on our data,
      aneuploidy assays such as sperm-fluorescence in situ hybridization assay and
      micronucleus test complemented by fluorescence in situ hybridization with
      centromeric DNA probes have been to some extent validated to be recommended for
      the assessment of aneuploidogenic effects of chemicals.

PMID- 21856315
TI  - Neuropeptidomics of mouse hypothalamus after imipramine treatment reveal
      somatostatin as a potential mediator of antidepressant effects.
AB  - Excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis has been
      associated with numerous diseases, including depression, and the tricyclic
      antidepressant imipramine has been shown to suppress activity of the HPA axis.
      Central hypothalamic control of the HPA axis is complex and involves a number of
      neuropeptides released from multiple hypothalamic subnuclei. The present study
      was therefore designed to determine the effects of imipramine administration on
      the mouse hypothalamus using a peptidomics approach. Among the factors found to
      be downregulated after acute (one day) or chronic (21 days) imipramine
      administration were peptides derived from secretogranin 1 (chromogranin B) as
      well as peptides derived from cerebellin precursors. In contrast, peptides SRIF
      14 and SRIF-28 (1-11) derived from somatostatin (SRIF, somatotropin release
      inhibiting factor) were significantly upregulated by imipramine in the
      hypothalamus. Because diminished SRIF levels have long been known to occur in
      depression, a second part of the study investigated the roles of individual SRIF
      receptors in mediating potential antidepressant effects. SRA880, an antagonist of
      the somatostatin-1 autoreceptor (sst1) which positively modulates release of
      endogenous SRIF, was found to synergize with imipramine in causing antidepressant
      like effects in the tail suspension test. Furthermore, chronic co-administration
      of SRA880 and imipramine synergistically increased BDNF mRNA expression in the
      cerebral cortex. Application of SRIF or L054264, an sst2 receptor agonist, but
      not L803807, an sst4 receptor agonist, increased phosphorylation of CaMKII and
      GluR1 in cerebrocortical slices. Our present experiments thus provide evidence
      for antidepressant-induced upregulation of SRIF in the brain, and strengthen the
      notion that augmented SRIF expression and signaling may counter depressive-like
      symptoms. This article is part of a Special Issue entitled 'Anxiety and
      Depression'.

PMID- 21856316
TI  - Increased expression of dysbindin-1A leads to a selective deficit in NMDA
      receptor signaling in the hippocampus.
AB  - The effects of the major schizophrenia susceptibility gene disease DTNBP1 on
      disease risk are likely to be mediated through changes in expression level of the
      gene product, dysbindin-1. How such changes might influence pathogenesis is,
      however, unclear. One possible mechanism is suggested by recent work establishing
      a link between altered dysbindin-1 expression and changes in surface levels of N
      methyl-d-aspartate receptors (NMDAR), although neither the precise nature of this
      relationship, nor the mechanism underlying it, are understood. Using organotypic
      slices of rat hippocampus, we show that increased expression of dysbindin-1A in
      pyramidal neurons causes a severe and selective hypofunction of NMDARs and blocks
      induction of LTP. Cell surface, but not cytoplasmic, expression of the NR1
      subunit of the NMDAR is decreased, suggesting dysregulation of NMDAR trafficking
      and, consistent with this, pharmacological inhibition of clathrin-dependent
      endocytosis is sufficient to reverse the deficit in NMDAR signaling. These
      results support the idea that the level of the NMDAR at the plasma membrane is
      modulated by changes in dysbindin-1 expression and offer further insight into the
      role of dysbindin-1 at an important cellular pathway implicated in schizophrenia.

PMID- 21856317
TI  - Selective phosphodiesterase inhibitors improve performance on the ED/ID cognitive
      task in rats.
AB  - A number of selective phosphodiesterase (PDE) inhibitors have been demonstrated
      to improve learning in several rodent models of cognition. Given that
      schizophrenia is associated with impairments in frontal lobe-dependent cognitive
      functions (e.g., working memory and cognitive flexibility), we examined whether
      PDE inhibitors would attenuate cognitive deficits associated with schizophrenia.
      Persistent suppression of N-methyl-D-aspartate (NMDA) receptor function produces
      enduring structural changes in neocortical and limbic regions in a pattern
      similar to changes reported in schizophrenia. This similarity suggests that
      subchronic treatment with NMDA receptor antagonists (e.g., phencyclidine, PCP)
      may represent a useful preclinical model of neurobiological and related cognitive
      deficits associated with schizophrenia. We treated male Long-Evans rats with
      subchronic PCP (5 mg/kg, ip, BID, 7 d) or saline and then examined the effects of
      acute treatment with selected doses of PDE inhibitors that have been demonstrated
      to regulate both intracellular levels of cAMP and/or cGMP, and to improve
      cognitive function. We used an extradimensional-intradimensional (ED/ID) test of
      cognitive flexibility similar to those used in humans and non-human primates for
      assessing executive function. Subchronic treatment with PCP produced a selective
      impairment on ED shift (EDS) performance without significant impairment on any
      other discrimination problem when compared to saline-treated control animals.
      Selected doses of the four PDEIs evaluated (PDE2: BAY 60-7550; PDE4: rolipram;
      PDE5: sildenafil; PDE10A: papaverine) were able to significantly attenuate this
      cognitive deficit in EDS performance. This suggests that this rodent model of
      executive function was sensitive to pro-cognitive effects of intracellular
      effects resulting from PDE inhibition. Together, these data suggest that
      inhibition of PDE activity may represent valuable therapeutic targets to improve
      cognition associated with neuropsychiatric disorders that feature cognitive
      dysfunction as a key symptom.

PMID- 21856319
TI  - Understanding facial emotion perception in Parkinson's disease: the role of
      configural processing.
AB  - Parkinson's disease (PD) has been frequently associated with facial emotion
      recognition impairments, which could adversely affect the social functioning of
      those patients. Facial emotion recognition requires processing of the spatial
      relations between facial features, known as the facial configuration. Few
      studies, however, have investigated this ability in people with PD. We
      hypothesized that facial emotion recognition impairments in patients with PD
      could be accounted for by a deficit in configural processing. To assess this
      hypothesis, three tasks were proposed to 10 patients with PD and 10 healthy
      controls (HC): (i) a facial emotion recognition task with upright faces, (ii) a
      similar task with upside-down faces, to explore the face inversion effect, and
      (iii) a configural task to assess participants' abilities to detect configural
      modifications made on a horizontal or vertical axis. The results showed that when
      compared with the HC group, the PD group had impaired facial emotion recognition,
      in particular for faces expressing anger and fear, and exhibited reduced face
      inversion effect for these emotions. More importantly, the PD group's performance
      on the configural task to detect vertical modifications was lower than the HC
      group's. Taken together, these results suggest the presence of a configural
      processing alteration in patients with PD, especially for vertical, second-order
      information. Furthermore, configural performance was positively correlated with
      emotion recognition for anger, disgust, and fear, suggesting that facial emotion
      recognition could be related, at least partially, to configural processing.

PMID- 21856320
TI  - Attention and the readiness for action.
AB  - The initiation of voluntary action is preceded by up to 2s of preparatory neural
      activity, originating in premotor and supplementary motor regions of the brain.
      The function of this extended period of pre-movement activity is unclear.
      Although recent studies have suggested that pre-movement activity is influenced
      by attention to action, little is understood about the specific processes that
      are involved in this preparatory period prior to voluntary action. We recorded
      readiness potentials averaged from EEG activity as participants made voluntary
      self-paced finger movements. We manipulated the processing resources available
      for action preparation using concurrent perceptual load and cognitive working
      memory load tasks. Results showed that pre-movement activity was significantly
      reduced only under conditions of high working memory load, when resources for
      planning action were limited by the concurrent cognitive load task. In contrast,
      limiting attentional resources in the perceptual load task had no effect on pre
      movement readiness activity. This suggests that movement preparatory processes
      involve mechanisms of cognitive control that are also required for working
      memory, and not more general engagement of selective attentional resources. We
      propose that the extended period of pre-movement neural activity preceding
      voluntary action reflects the engagement of cognitive control mechanisms for
      endogenously orienting attention in time, in readiness for the initiation of
      voluntary action.

PMID- 21856321
TI  - Impaired context reversal learning, but not cue reversal learning, in patients
      with amnestic mild cognitive impairment.
AB  - It has been proposed that reversal learning is impaired following damage to the
      orbitofrontal and ventromedial frontal cortex (OFC/VMFC) and to the medial
      temporal lobe (MTL), including the hippocampal formation. However, the exact
      characteristics of the MTL-associated reversal learning deficit are not known. To
      investigate this issue, we assessed 30 newly diagnosed patients with amnestic
      mild cognitive impairment (aMCI) and 30 matched healthy controls. All patients
      fulfilled the aMCI criteria of the Mayo Clinic Alzheimer's Disease Research
      Center and underwent head magnetic resonance imaging that confirmed MTL atrophy.
      Reversal learning was assessed using a novel reinforcement learning task.
      Participants first acquired and then reversed stimulus-outcome associations based
      on negative and positive feedback (losing and gaining points). Stimuli consisted
      of a cue (geometric shapes) and a spatial context (background color or pattern).
      Neuropsychological assessment included tasks related to the MTL (paired
      associates learning), dorsolateral prefrontal cortex (DLPFC) (extradimensional
      shift, One-touch Stockings of Cambridge), and OFC/VMFC (Holiday Apartment Task).
      Results revealed that, relative to controls, patients with aMCI exhibited a
      marked reversal learning deficit, which was highly selective for the reversal of
      context. The acquisition of stimulus-outcome associations and cue reversal
      learning were spared. Performance on the context reversal learning task
      significantly correlated with the right hippocampal volume. In addition, patients
      with aMCI had deficits on tests related to DLPFC but not to OFC/VMFC. However,
      DLPFC dysfunctions were not associated with context reversal learning. These
      results suggest that MTL deficits in aMCI selectively affect context reversal
      learning when OFC/VMFC functions are spared. This deficit is not influenced by
      the valence of the outcome (positive or negative feedback) and by executive
      dysfunctions.

PMID- 21856322
TI  - Effects of neuroactive steroids on cochlear hair cell death induced by
      gentamicin.
AB  - As neuroactive steroids, sex steroid hormones have non-reproductive effects. We
      previously reported that 17beta-estradiol (betaE2) had protective effects against
      gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined
      whether the protective action of betaE2 on GM ototoxicity is mediated by the
      estrogen receptor (ER) and whether other estrogens (17alpha-estradiol (alphaE2),
      estrone (E1), and estriol (E3)) and other neuroactive steroids,
      dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective
      effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley
      rats and cultured in a medium containing 100 MUM GM for 48h. The effects of
      betaE2 and ICI 182,780, a selective ER antagonist, were examined. In addition,
      the effects of other estrogens, DHEA and P were tested using this culture system.
      Loss of outer hair cells induced by GM exposure was compared among groups. betaE2
      exhibited a protective effect against GM ototoxicity, but its protective effect
      was antagonized by ICI 182,780. alphaE2, E1, and E3 also protected hair cells
      against gentamicin ototoxicity. DHEA showed a protective effect; however, the
      addition of ICI 182,780 did not affect hair cell loss. P did not have any effect
      on GM-induced outer hair cell death. The present findings suggest that estrogens
      and DHEA are protective agents against GM ototoxicity. The results of the ER
      antagonist study also suggest that the protective action of betaE2 is mediated
      via ER but that of DHEA is not related to its conversion to estrogen and binding
      to ER. Further studies on neuroactive steroids may lead to new insights regarding
      cochlear protection.

PMID- 21856318
TI  - Extracellular matrix abnormalities in schizophrenia.
AB  - Emerging evidence points to the involvement of the brain extracellular matrix
      (ECM) in the pathophysiology of schizophrenia (SZ). Abnormalities affecting
      several ECM components, including Reelin and chondroitin sulfate proteoglycans
      (CSPGs), have been described in subjects with this disease. Solid evidence
      supports the involvement of Reelin, an ECM glycoprotein involved in
      corticogenesis, synaptic functions and glutamate NMDA receptor regulation,
      expressed prevalently in distinct populations of GABAergic neurons, which secrete
      it into the ECM. Marked changes of Reelin expression in SZ have typically been
      reported in association with GABA-related abnormalities in subjects with SZ and
      bipolar disorder. Recent findings from our group point to substantial
      abnormalities affecting CSPGs, a main ECM component, in the amygdala and
      entorhinal cortex of subjects with schizophrenia, but not bipolar disorder.
      Striking increases of glial cells expressing CSPGs were accompanied by reductions
      of perineuronal nets, CSPG- and Reelin-enriched ECM aggregates enveloping
      distinct neuronal populations. CSPGs developmental and adult functions, including
      neuronal migration, axon guidance, synaptic and neurotransmission regulation are
      highly relevant to the pathophysiology of SZ. Together with reports of anomalies
      affecting several other ECM components, these findings point to the ECM as a key
      component of the pathology of SZ. We propose that ECM abnormalities may
      contribute to several aspects of the pathophysiology of this disease, including
      disrupted connectivity and neuronal migration, synaptic anomalies and altered
      GABAergic, glutamatergic and dopaminergic neurotransmission.

PMID- 21856323
TI  - Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer
      cell lines: the role of glutathione.
AB  - We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi
      drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a
      viable mechanism to sensitize cancer cells to chemotherapies. This concept was
      demonstrated using chrysin (5-25 MUM) induced GSH efflux in human non-small cell
      lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX).
      Treatment with chrysin resulted in significant and sustained intracellular GSH
      depletion and the GSH enzyme network in the four cancer cell types was predictive
      of the severity of chrysin induced intracellular GSH depletion. Gene expression
      data indicated a positive correlation between basal MRP1, MRP3 and MRP5
      expression and total GSH efflux before and after chrysin exposure. Co-treating
      the cells for 72 h with chrysin (5-30 MUM) and DOX (0.025-3.0 MUM) significantly
      enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone
      treatment in all four cell lines. The maximum decrease in the IC(50) values of
      cells treated with DOX alone compared to co-treatment with chrysin and DOX was
      43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin
      worked synergistically with DOX to induce cancer cell death. This approach could
      allow for use of lower concentrations and/or sensitize cancer cells to drugs that
      are typically resistant to therapy.

PMID- 21856325
TI  - Special issue: Environmental chemicals and neurotoxicity.

PMID- 21856324
TI  - Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and
      autophagy in dopaminergic neuronal cells.
AB  - The production of man-made nanoparticles for various modern applications has
      increased exponentially in recent years, but the potential health effects of most
      nanoparticles are not well characterized. Unfortunately, in vitro nanoparticle
      toxicity studies are extremely limited by yet unresolved problems relating to
      dosimetry. In the present study, we systematically characterized manganese (Mn)
      nanoparticle sizes and examined the nanoparticle-induced oxidative signaling in
      dopaminergic neuronal cells. Differential interference contrast (DIC) microscopy
      and transmission electron microscopy (TEM) studies revealed that Mn nanoparticles
      range in size from single nanoparticles (~25 nM) to larger agglomerates when in
      treatment media. Manganese nanoparticles were effectively internalized in N27
      dopaminergic neuronal cells, and they induced a time-dependent upregulation of
      the transporter protein transferrin. Exposure to 25-400 MUg/mL Mn nanoparticles
      induced cell death in a time- and dose-dependent manner. Mn nanoparticles also
      significantly increased ROS, accompanied by a caspase-mediated proteolytic
      cleavage of proapoptotic protein kinase Cdelta (PKCdelta), as well as activation
      loop phosphorylation. Blocking Mn nanoparticle-induced ROS failed to protect
      against the neurotoxic effects, suggesting the involvement of other pathways.
      Further mechanistic studies revealed changes in Beclin 1 and LC3, indicating that
      Mn nanoparticles induce autophagy. Primary mesencephalic neuron exposure to Mn
      nanoparticles induced loss of TH positive dopaminergic neurons and neuronal
      processes. Collectively, our results suggest that Mn nanoparticles effectively
      enter dopaminergic neuronal cells and exert neurotoxic effects by activating an
      apoptotic signaling pathway and autophagy, emphasizing the need for assessing
      possible health risks associated with an increased use of Mn nanoparticles in
      modern applications.

PMID- 21856326
TI  - Abortion in goats after experimental administration of Stryphnodendron fissuratum
      (Mimosoideae).
AB  - The abortive properties and the clinical and pathological features of poisoning
      by the pods of Stryphnodendron fissuratum were studied in 8 pregnant goats. Two
      goats that ingested 3.25 g/kg body weight daily doses for 2 days, and 2 that
      ingested 2.5 g/kg daily doses for 3 days showed digestive clinical signs and
      aborted, but the animals that ingested 3 daily doses of 2.5 g/kg died. Lesions of
      the digestive system and liver were observed at necropsy. Two goats that ingested
      a single dose of 5.5 g/kg showed mild clinical signs and recovered without
      abortion. Another 2 goats that ingested single doses of 5 g/kg showed no clinical
      signs. These results demonstrate that Stryphnodendron fisuratum pods cause
      digestive disorders, liver disease, abortion and death.

PMID- 21856327
TI  - Motion aftereffect duration is not changed by perceptual learning: evidence
      against the representation modification hypothesis.
AB  - The representation modification hypothesis of perceptual learning attributes the
      practice-induced improvements in sensitivity and/or discriminability to changes
      in the early visual areas. We used motion aftereffects (MAE) to probe the
      representations of motion direction. In two experiments, four practice sessions
      on a fine direction-discrimination task caused large stimulus-specific
      improvements in d' but no significant stimulus-specific changes in either static
      or dynamic MAE duration at posttest relative to a pretest. Power analysis
      indicated that the data were approximately 100 times more likely given the
      hypothesis of no MAE change than the hypothesis of a 10% relative change. In
      light of converging evidence in the MAE literature, this suggests that little or
      no change occurred in the cortical representations of visual motion up to and
      including area MT. The task specificity of the learning effect challenges the
      representation modification hypothesis and supports an alternative-selective
      reweighting.

PMID- 21856328
TI  - Exposure to radio frequency electromagnetic fields from wireless computer
      networks: duty factors of Wi-Fi devices operating in schools.
AB  - The growing use of wireless local area networks (WLAN) in schools has prompted a
      study to investigate exposure to the radio frequency (RF) electromagnetic fields
      from Wi-Fi devices. International guidelines on limiting the adverse health
      effects of RF, such as those of ICNIRP, allow for time-averaging of exposure.
      Thus, as Wi-Fi signals consist of intermittent bursts of RF energy, it is
      important to consider the duty factors of devices in assessing the extent of
      exposure and compliance with guidelines. Using radio packet capture methods, the
      duty factor of Wi-Fi devices has been assessed in a sample of 6 primary and
      secondary schools during classroom lessons. For the 146 individual laptops
      investigated, the range of duty factors was from 0.02 to 0.91%, with a mean of
      0.08% (SD 0.10%). The duty factors of access points from 7 networks ranged from
      1.0% to 11.7% with a mean of 4.79% (SD 3.76%). Data gathered with transmit time
      measuring devices attached to laptops also showed similar results. Within the
      present limited sample, the range of duty factors from laptops and access points
      were found to be broadly similar for primary and secondary schools. Applying
      these duty factors to previously published results from this project, the maximum
      time-averaged power density from a laptop would be 220 MUW m(-2), at a distance
      of 0.5 m and the peak localised SAR predicted in the torso region of a 10 year
      old child model, at 34 cm from the antenna, would be 80 MUW kg(-1).

PMID- 21856329
TI  - Interactions of collagen molecules in the presence of N-hydroxysuccinimide
      activated adipic acid (NHS-AA) as a crosslinking agent.
AB  - The effect of crosslinking agent on pepsin-soluble bovine collagen solution was
      examined using N-hydroxysuccinimide activated adipic acid (NHS-AA) as a
      crosslinker. Electrophoretic patterns indicated that crosslinks formed when NHS
      AA was added. A higher polarity level deduced from the changes in the
      fluorescence emission spectrum of pyrene in the crosslinked collagen solution
      indicated that the formation of well-ordered aggregates was suppressed. The
      random aggregation of collagens was also observed by atomic force microscopy
      (AFM). Furthermore, the association of collagens into fibrils was influenced by
      crosslinking. Self-assembly was suppressed at 37 degrees C; however, as
      temperature was increased to 39 degrees C, a small amount of NHS-AA leaded to an
      improvement in the ability of self-aggregation. Although more random structure
      was brought about by crosslinking, self-aggregation might still be promoted as
      temperature was increased, accompanying by the thermal stability improvement of
      fibrils.

PMID- 21856330
TI  - Immobilization of rat brain acetylcholinesterase on porous gold-nanoparticle
      CaCO3 hybrid material modified Au electrode for detection of organophosphorous
      insecticides.
AB  - An acetylcholinesterase (AChE) purified from rat brain was immobilized onto gold
      nanoparticles (AuNPs) assembled on the surface of porous calcium carbonate
      (CaCO(3)) microsphere. The resulting AChE-AuNPs-CaCO(3) bioconjugate was mounted
      on the surface of Au electrode with the help of silica sol-gel matrix to prepare
      the working electrode. This electrode was connected to Ag/AgCl (3M/saturated KCl)
      as standard and Pt wire as an auxiliary electrode through a potentiostat to
      construct an organophosphorus (OP) biosensor. The biosensor was based on
      inhibition of AChE by OP compounds/insecticides. The biosensor showed optimum
      response at pH 7.0, 30 degrees C, when polarized at +0.2V. Two OP compounds,
      malathion and chlorpyrifos could be detected in the range of 0.1-100 nM and 0.1
      70 nM, respectively at 2.0-3.0% inhibition level of AChE. The sensor was
      reactivated by immersing it in 0.1 mM 2-pyridine aldoxime for 10 min. The
      detection limit of the sensor was 0.1 nM for both malathion and chlorpyrifos. The
      biosensor exhibited good reusability (50 times without considerable loss) and
      storage stability (50% within 60 days, when stored at 4 degrees C).

PMID- 21856331
TI  - Quinolinic acid lesions of the pedunculopontine nucleus impair sleep
      architecture, but not locomotion, exploration, emotionality or working memory in
      the rat.
AB  - Anatomical and functional studies have shown that the NADPH-diaphorase-positive
      cholinergic neurons of the pedunculopontine nucleus (PPN) send projections to
      several areas in the brain. The purpose of this work was to investigate whether
      bilateral lesions with quinolinic acid, a neurotoxin with greater selectivity for
      NADPH-diaphorase-positive neurons, aimed at the compact portion of the PPN would
      affect the performance of adaptive behaviors, such as sleep, locomotion, and
      spontaneous alternation. Lesioned animals were divided in a low lesion group (LL,
      <50% neuron loss) and a high lesion group (HL, >=50% neuron loss). The LL animals
      did not show any significant changes in sleep patterns, as compared to controls.
      In contrast, the HL group showed a significant increase in the number of REM
      sleep periods, and a reduction of REM sleep average duration, but did not differ
      in the total time spent in REM sleep. HL animals also showed an increase in the
      number of SWS periods, though wakefulness parameters did not show significant
      alterations. The duration and number of both REM and SWS sleep episodes were
      significantly correlated with the number of NADPH-diaphorase-positive neurons in
      the PPN. The short-term habituation pattern of locomotion, the vertical
      exploratory activity, as well as the thigmotaxis (an index of emotionality),
      displayed by LL and HL rats in a novel environment were similar to those of
      control animals. Likewise, there were no significant differences in spontaneous
      alternation among the groups. Our results indicate that quinolinic acid lesions
      of NADPH-diaphorase-positive cholinergic neurons localized in the posterior
      region of the PPN disrupt normal sleep structure, while motor activity and
      spontaneous alternation remain unaffected.

PMID- 21856332
TI  - Persistent cognitive deficits, induced by intrathecal methotrexate, are
      associated with elevated CSF concentrations of excitotoxic glutamate analogs and
      can be reversed by an NMDA antagonist.
AB  - For patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma,
      intrathecal (IT) methotrexate (MTX) significantly reduces the risk of relapse
      within the central nervous system, but is associated with neurotoxic sequelae. We
      established a rat model of MTX-induced cognitive deficits to further investigate
      the underlying pathophysiology and to develop protective therapeutic
      interventions. IT MTX 0.5 mg/kg was administered to 10-week old male Long Evans
      rats. Cerebrospinal fluid (CSF) was collected for measurement of folate,
      homocysteine, and excitotoxic glutamate analogs. Recognition and spatial memory
      were tested in the novel object recognition (NOR) task and the object placement
      (OP) task, respectively. Four doses of IT MTX in a two-week period induced
      cognitive deficits persisting at least three months after the final injection.
      CSF concentrations of the excitotoxic glutamate analogs homocysteic acid and
      homocysteine sulfinic acid were increased relative to baseline for the same three
      month period. Dextromethorphan, a noncompetitive antagonist at the N-methyl-D
      aspartate receptor, administered at a dose of 2 mg/kg intraperitoneally twice
      daily for a total of four doses, improved cognitive function among the MTX
      treated rats, with no effect on control rats. Although this improvement was
      transient, each repeated treatment with dextromethorphan was followed by
      normalization of cognitive function. In conclusion, IT MTX induces persistent
      alterations in glutaminergic tone that may contribute to persistent cognitive
      deficits. Treatment with a glutamate receptor antagonist such as dextromethorphan
      may ameliorate the negative cognitive outcomes observed among patients with
      leukemia or lymphoma treated with repeated doses of prophylactic IT MTX.

PMID- 21856333
TI  - Inhibition of PKA attenuates memory deficits induced by beta-amyloid (1-42), and
      decreases oxidative stress and NF-kappaB transcription factors.
AB  - Alzheimer's disease (AD), the most relevant cause of dementia in elderly, is
      characterized by amyloid beta (Abeta) containing plaques and neurofibrillatory
      tangles, synaptic and neuronal loss, along with progressive cognitive impairment
      in short-term memory. However, mechanistic links between protein kinase A (PKA),
      oxidative stress and memory loss in response to Abeta remain elusive. In the
      present study, we examined the effects of post-training bilateral intra
      hippocampal infusions of the specific protein kinase AII inhibitor, H-89, on
      memory deficits induced by Abeta (1-42) in Abeta-pretreated rats. H-89 and Abeta
      were administered immediately after completion of training. All animals were
      trained for 4 consecutive days and tested 9 and 19 days after the infusions.
      Significant differences were observed in the time and distance of finding the
      hidden platform in Abeta treated animals after 19 days. Interestingly, intra
      hippocampal infusion of H-89 (5MUM/side) significantly prevented the Abeta
      induced memory impairment. Furthermore, evaluation of NFkappaB (nuclear factor
      kappaB), and antioxidant enzymes, such as gamma-GCS (glutamylcysteine
      synthetase), HO-1 (hemeoxygenase-1), GSH (glutathione), and SOD (superoxide
      dismutase) confirmed the protective effect of H-89. Given the possible
      neuroprotective effects of H-89 on Abeta-induced memory impairment, our results
      may open a new avenue for the prevention of AD by PKAII signaling pathway
      inhibitor.

PMID- 21856334
TI  - Effects of ventral tegmental area stimulation on the acquisition and long-term
      retention of active avoidance learning.
AB  - The development of avoidance learning depends on dopamine release in forebrain
      regions. Previous studies indicated that rewarding brain stimulation facilitated
      two-way active avoidance learning. However, it is not clear whether the temporal
      relationship of brain stimulation to the training session (before, during or
      after) is important. To investigate the role of stimulation condition (no
      stimulation, self-stimulation only, or self-stimulation plus avoidance
      stimulation) and sequence of self-stimulation training (before or after avoidance
      training), we used a 3*2 factorial design, in which every level of stimulation
      was paired with every level of sequence for a total of 6 different groups. The
      results suggest that self-stimulation either before or after avoidance learning
      improved acquisition performance, but acquisition was maximal when stimulation
      was also given during acquisition trials. Importantly, the sequence of self
      stimulation (before or after each acquisition session) was irrelevant to this
      beneficial effect. However, stimulation had no apparent effect on long-term
      retention when tested 10 days later under conditions of no stimulation, except
      that the performance of the group that had previously received avoidance
      contingent stimulation deteriorated over the course of 60 trials. This may
      reflect frustration from the omission of expected reward. These results are
      relevant for optimizing brain stimulation to improve learning.

PMID- 21856335
TI  - Functions for adult neurogenesis in memory: an introduction to the
      neurocomputational approach and to its contribution.
AB  - Until recently, it was believed that the introduction of new neurons in neuronal
      networks was incompatible with memory function. Since the rediscovery of adult
      hippocampal neurogenesis, behavioral data demonstrate that adult neurogenesis is
      required for memory processing. We examine neurocomputational studies to identify
      which basic mechanisms involved in memory might be mediated by adult
      neurogenesis. Mainly, adult neurogenesis might be involved in the reduction of
      catastrophic interference and in a time-related pattern separation function.
      Artificial neuronal networks suggest that the selective recruitment of new-born
      or old neurons is not stochastic, but depends on environmental requirements. This
      leads us to propose the novel concept of "soft-supervision". Soft-supervision
      would be a biologically plausible process, by which the environment is able to
      influence activation and learning rules of neurons differentially.

PMID- 21856336
TI  - Electrical stimulation over the left inferior frontal gyrus (IFG) determines long
      term effects in the recovery of speech apraxia in three chronic aphasics.
AB  - A number of studies have shown that modulating cortical activity by means of
      transcranial direct current stimulation (tDCS) affects the performance of both
      healthy and brain-damaged subjects. In this study, we investigated the potential
      of tDCS for the recovery of apraxia of speech in 3 patients with stroke-induced
      aphasia. Over 2 weeks, three aphasic subjects participated in a randomized double
      blinded experiment involving intensive language training for their articulatory
      difficulties in two tDCS conditions. Each subject participated in five
      consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation
      over the left inferior frontal gyrus (referred to as Broca's area) while they
      performed a repetition task. By the end of each week, a significant improvement
      was found in both conditions. However, all three subjects showed greater response
      accuracy in the anodic than in the sham condition. Moreover, results for transfer
      of treatment effects, although different across subjects, indicate a
      generalization of the recovery at the language test. Subjects 2 and 3 showed a
      significant improvement in oral production tasks, such as word repetition and
      reading, while Subjects 1 and 2 had an unexpected significant recovery in written
      naming and word writing under dictation tasks. At three follow-ups (1 week, 1 and
      2 months after the end of treatment), response accuracy was still significantly
      better in the anodic than in sham condition, suggesting a long-term effect on the
      recovery of their articulatory gestures.

PMID- 21856337
TI  - How one's favorite song activates the reward circuitry of the brain: personality
      matters!
AB  - The present fMRI study investigates individual differences in human brain
      activity during listening to one's favorite and one's most unlikeable song. In 33
      participants, we found that the contrast of listening to pleasant versus
      unpleasant music revealed a robust activation of the ventral striatum, the
      caudate nucleus and the insula across a group of participants. Moreover, we could
      demonstrate that activity within the ventral striatum was modulated by the
      subscale 'self-forgetfulness' of the character dimension 'self-transcendence'.

PMID- 21856338
TI  - The primase domain of PfPrex is a proteolytically matured, essential enzyme of
      the apicoplast.
AB  - The apicoplast of Plasmodium is an essential organelle with its own circular
      genome that must be faithfully replicated and segregated to its progeny during
      parasite sporogony and schizogony. DNA replication proteins are not encoded by
      its genome. Instead, the replication machinery must be imported from nuclear
      encoded genes. A likely apicoplast DNA replication factor, PfPrex, bears a
      bipartite leader sequence for apicoplast trafficking and contains several DNA
      replication-related enzymatic domains. Here we analyze the domain structure of
      PfPrex and examine its trafficking and maturation within the parasite. A minimal
      primase domain of PfPrex is shown to contain functional zinc-binding and TOPRIM
      fold domains, which in a recombinant form are sufficient to produce RNA primers
      from a single-stranded DNA template. PfPrex is shown to be extensively
      proteolytically matured within the parasite, which effectively separates its
      functional domains. Gene targeting attempts to knockout the Plasmodium yoelii
      ortholog of Prex were unsuccessful, indicating the apparent essentiality of this
      protein to the parasite. Finally, overexpression in Plasmodium falciparum of
      PfPrex's trafficking and primase sequences yielded specific and dynamic
      localization to foci within the apicoplast. Taken together, these observations
      strongly suggest an essential role of PfPrex primase in the production of RNA
      primers for lagging strand DNA synthesis of the apicoplast genome.

PMID- 21856340
TI  - The survival effect of mitochondrial Higd-1a is associated with suppression of
      cytochrome C release and prevention of caspase activation.
AB  - Higd-1a (hypoxia induced gene domain family-1a) is a mitochondrial inner membrane
      protein with a conformation of N-terminal outside-C-terminal outside and loop
      inside. There are four Higd genes, Higd-1a, -1b, -1c and -2a, in the mouse. Higd
      1a and -2a are expressed primarily in the brain, heart, kidney and leukocytes.
      HIF (hypoxia-inducible factor) overexpression induced the endogenous expression
      and promoter activity of Higd-1a. Mutation of the HRE (hypoxia-response element)
      site at -32bp in the Higd-1a promoter reduced the promoter activity, suggesting
      that transcription of Higd-1a is regulated by binding of the transcription factor
      HIF to the HRE. Higd-1a promoted cell survival under hypoxia. RAW264.7 cells
      stably transfected with Higd-1a underwent less apoptosis than control cells in a
      hypoxic condition, and hypoxia-induced apoptosis was strongly enhanced when
      endogenous Higd-1a was silenced by siRNA. The survival effect of Higd-1a was
      completely abolished by deletion of the 26 N-terminal amino acids, and we showed
      that Higd-1a increased survival by inhibiting cytochrome C release and reducing
      the activities of caspases. However, expression of Bcl-2, Bax, Bad, and BNIP3 and
      translocation of AIF were unaffected under the same conditions. Higd-2a also
      enhanced cell survival under hypoxia. Cells transfected with Higd-2a underwent
      less apoptosis than control cells in hypoxic conditions, and hypoxia-induced
      apoptosis increased when endogenous Higd-2a was depleted. Together these
      observations indicate that Higd-1a is induced by hypoxia in a HIF-dependent
      manner and its anti-apoptotic effect results from inhibiting cytochrome C release
      and reducing caspase activities.

PMID- 21856341
TI  - Isolation and identification of quorum quenching bacteria from environmental
      samples.
AB  - A large number of Gram-negative pathogens produce N-acylhomoserine lactones
      (AHLs) as signal molecules for quorum sensing (QS). This cell-cell communication
      system allows them to coordinate gene expression and regulate virulence.
      Therefore, strategies to inhibit QS are promising for the control of infectious
      diseases. The aim of the present study was to develop a high-throughput method
      for the isolation and identification of AHL-degrading bacteria from environmental
      samples. Samples were cultured in a microtitre plate in a minimal medium
      containing 1 mM N-(3-oxo-dodecanoyl)-L-homoserine lactone and 2 mM N-(3-oxo
      hexanoyl)-L-homoserine lactone as the sole sources of carbon and nitrogen.
      Isolates growing on this minimal medium were subcultured and identified by
      partial 16S rRNA gene sequencing. Subsequently, the AHL-degrading capacity of
      each isolate was evaluated in the Pseudomonas aeruginosa QSIS2 biosensor assay,
      as such or after treatment with heat or proteinase K. The 16 samples tested
      yielded a total of 59 isolates which are, either alone or as part of a
      consortium, able to use AHL signal molecules as sole sources of carbon and
      nitrogen. Follow-up experiments have shown that in each sample there is at least
      one isolate with quorum quenching (QQ) activity, and that for all samples
      combined, 41 isolates have QQ activity. Furthermore, heat treatment did not fully
      inhibit QQ activity in all isolates. In some isolates, QQ activity was lost after
      proteinase K treatment, while others remained able to quench QS. Therefore, it is
      likely that some isolates produce and secrete (a) heat-stable, low molecular
      weight inhibitory compound(s).

PMID- 21856339
TI  - Post-translational modifications of Hsp90 and their contributions to chaperone
      regulation.
AB  - Molecular chaperones, as the name suggests, are involved in folding, maintenance,
      intracellular transport, and degradation of proteins as well as in facilitating
      cell signaling. Heat shock protein 90 (Hsp90) is an essential eukaryotic
      molecular chaperone that carries out these processes in normal and cancer cells.
      Hsp90 function in vivo is coupled to its ability to hydrolyze ATP and this can be
      regulated by co-chaperones and post-translational modifications. In this review,
      we explore the varied roles of known post-translational modifications of
      cytosolic and nuclear Hsp90 (phosphorylation, acetylation, S-nitrosylation,
      oxidation and ubiquitination) in fine-tuning chaperone function in eukaryotes.
      This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

PMID- 21856342
TI  - Enhancement of activity of cross-linked enzyme aggregates by a sugar-assisted
      precipitation strategy: technical development and molecular mechanism.
AB  - The precipitation of enzyme causes the major activity loss in the conventional
      protocol for CLEAs preparation. Herein, a sugar-assisted strategy was developed
      to minimize the activity loss in the step of enzyme precipitation by adding sugar
      as the stabilizer, which contributed to improve the activity yield of resulting
      CLEAs. Penicillin G acylase (PGA) was employed as a model enzyme. The effects of
      glucose, sucrose and trehalose on the activity yields of CLEAs were investigated.
      The highest activity was obtained in the case of adding trehalose. Confocal laser
      scanning microscopy and Fourier transform infrared spectroscopy showed that the
      polar microenvironment and the secondary structure of native enzyme were
      preserved to some extent when PGA was prepared as sugar-assisted CLEAs, resulting
      in PGA's higher activity than sugar-free CLEAs. Scanning electron microscope
      revealed the different inner morphologies, and the kinetic studies showed the
      higher affinity and resist-inhibition capacity of sugar-assisted CLEAs.
      Furthermore, stability experiments demonstrated that CLEAs prepared in sugar
      assisted strategy remained higher thermal stability when it was incubated at high
      temperature.

PMID- 21856343
TI  - Benefits of new tools in biotechnology to developing countries in south Asia: a
      perspective from UNESCO.
AB  - South Asia, once considered as a laggard, has grown at about 6% on average over
      the past two decades and the current growth outlook is much brighter. However,
      this growth is not always well distributed and the challenges of
      institutionalising policies and mechanisms to ensure inclusive growth are now
      being seriously considered by these countries governments. The targets set by
      south Asian countries are primarily based on the investments in infrastructural
      sector with an objective to generate educated and skilled human resources. The
      other most important inclusive growth area is the core public services;
      Agriculture, Health, and Energy, which are increasingly becoming technology
      driven. Biotechnology has been increasingly seen now to be an area of technology
      that holds the greatest new potential to address problems arising from low
      productivity, overburdened health systems, high-cost unsustainable energy
      supplies and the need for developing new materials for industrial and
      environmental applications. This article attempts to highlight perspectives on
      some of the emerging areas of biotechnology that have good potential for economic
      development in the context of south Asia, as well as discuss briefly some of
      UNESCO's initiatives in biotechnology for that region.

PMID- 21856344
TI  - Determination of phenanthrene bioavailability by using a self-dying reporter
      bacterium: test with model solids and soil.
AB  - The present study was conducted to investigate the performance and feasibility of
      a self-dying reporter bacterium to visualize and quantify phenanthrene
      bioavailability in soil. The self-dying reporter bacterium was designed to die on
      the initiation of phenanthrene biodegradation. The viability of the reporter
      bacterium was determined by a fluorescence live/dead cell staining method and
      visualized by confocal laser scanning microscopic observation. Phenanthrene was
      spiked into four types of model solids and a sandy loam. The bioavailability of
      phenanthrene to the reporter bacterium was remarkably declined with the
      hydrophobicity of the model solids: essentially no phenanthrene was biodegraded
      in the presence of 9-nm pores and about 35.8% of initial phenanthrene was
      biodegraded without pores. Decrease in bioavailability was not evident in the
      nonporous hydrophilic bead, but a small decrease was observed in the porous
      hydrophilic bead at 1000 mg/kg of phenanthrene. The fluorescence intensity was
      commensurate with the extent of phenanthrene biodegradation by the reporter
      bacterium at the concentration range from 50 to 500 mg/kg. Such a quantitative
      relationship was also confirmed with a sandy loam spiked up to 1000 mg/kg of
      phenanthrene. This reporter bacterium may be a useful means to determine
      phenanthrene bioavailability in soil.

PMID- 21856345
TI  - Thermal scanning probe microscopy in the development of pharmaceuticals.
AB  - The ability to characterize the physical and chemical properties of dosage forms
      is crucial to a more complete understanding of how vehicles for drug delivery
      behave and therefore how effective they are. Spatially resolved characterization
      that enables the visualization of properties on the nanoscale is particularly
      powerful. The usefulness of scanning probe microscopy (SPM) in the field of drug
      delivery is becoming increasingly well established and the use of thermal probes
      offers new capabilities thus enabling SPM to provide more and sometimes unique
      information. One type of measurement enabled by thermal probes is determining
      transition temperatures by means of local thermal analysis. The ability to
      identify and characterize materials in this way has found applications in
      characterizing a wide range of dosage forms. A complimentary thermal probe
      technique is photothermal infrared microspectroscopy (PTMS). PTMS offers a
      variety of advantages over more conventional approaches including the ability
      analyze compacts without the need for thin sections. It is also able to achieve
      sub-micron spatial resolution. Thermal probe techniques can characterize
      pharmaceutical dosage forms in terms of their physical properties and their
      chemical composition.

PMID- 21856346
TI  - Factors associated with eating out of home in Vietnamese adolescents.
AB  - Eating out of home (OH) is nutritionally important in some developing countries.
      This study identifies the factors associated with eating OH in Vietnamese
      adolescents. Data were obtained from a cross-sectional cluster survey of 502
      adolescents in rural and urban areas in Vietnam. Factors associated with eating
      OH were recorded with a Likert scale and analysed using factor analysis. Data on
      eating OH was collected using a frequency questionnaire and a 1-day 24h recall. A
      first pattern "Convenience" incorporated preparation time, price, variety, taste,
      proximity and social aspects as items associated with eating OH. A second pattern
      "Nutritional and food safety concerned" reflected concerns with regard to
      hygiene, fat and salt content of the food prepared OH. Adolescents characterised
      by the convenience pattern were more likely (OR=1.51, P<0.001) to eat OH more
      frequently. The highest tertile of the Nutritional and food safety concerned
      pattern was less likely (OR=0.61, P=0.03) to eat OH compared to lower tertiles.
      Both patterns were not associated with the % energy from eating OH per day.
      Convenience and to a lesser extent Nutritional and food safety concerns are
      significant factors associated with the frequency of eating OH in Vietnamese
      adolescents.

PMID- 21856347
TI  - Signaling through EAAT-1/GLAST in cultured Bergmann glia cells.
AB  - Glutamate, the major excitatory amino acid, activates a wide variety of signal
      transduction cascades. Synaptic plasticity relies on activity-dependent
      differential protein expression. Ionotropic and metabotropic glutamate receptors
      have been critically involved in long-term synaptic changes, although recent
      findings suggest that the electrogenic Na(+)-dependent glutamate transporters,
      responsible of its removal from the synaptic cleft, participate in glutamate
      induced signaling. Transporter proteins are expressed in neurons and glia cells
      albeit most of the glutamate uptake occurs in the glial compartment. Within the
      cerebellum, Bergmann glial cells are close to glutamatergic synapses and
      participate actively in the recycling of glutamate through the
      glutamate/glutamine shuttle. In this context, we decided to investigate a
      plausible role of Bergmann glia glutamate transporters as signaling entities. To
      this end, primary cultures of chick cerebellar Bergmann glial cells were exposed
      to d-aspartate (D-Asp) and other transporter ligands and the serine 2448
      phosphorylation pattern of the master regulator of protein synthesis, namely the
      mammalian target of rapamycin (mTOR), determined. An increase in mTOR
      phosphorylation and activity was detected. The signaling cascade included Ca(2+)
      influx, activation of the phosphatidylinositol 3-kinase and protein kinase B.
      Furthermore, transporter signaling resulted also in an increase in activator
      protein-1 (AP-1) binding to DNA and the up-regulation of the transcription of an
      AP-1 driven gene construct. These results add a novel mediator of the glutamate
      effects at the translational and transcriptional levels and further strengthen
      the notion of the critical involvement of glia cells in synaptic function.

PMID- 21856349
TI  - Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with
      hepatitis B vaccine: randomized study in healthy girls.
AB  - BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human
      papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine
      (HepB). METHODS: This was a randomized, controlled, open, multicenter study.
      Healthy girls, aged 9-15 years, were randomized to receive HPV (n=247), HepB
      (n=247) or HPV co-administered with HepB (HPV+HepB; n=247) at Months 0, 1 and 6.
      Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were
      measured, and reactogenicity and safety monitored. Co-primary objectives were to
      demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at
      Month 7 for co-administered vaccines, compared with vaccines administered alone,
      in the according-to-protocol cohort. RESULTS: The pre-defined criteria for non
      inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti
      HBs seroprotection rates >=10mIU/mL were achieved by 97.9% and 100% of girls,
      respectively, following co-administration or HepB alone. Anti-HBs geometric mean
      titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7
      (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18
      seroconversion rates were achieved by >=99% of girls following co-administration
      or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6
      (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were
      8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co
      administration was generally well tolerated. CONCLUSIONS: The study results
      support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis
      B vaccine in adolescent girls aged 9-15 years. CLINICAL TRIALS REGISTRATION:
      ClinicalTrials.gov registration number NCT00652938.

PMID- 21856350
TI  - Immunization with the recombinant antigen Ss-IR induces protective immunity to
      infection with Strongyloides stercoralis in mice.
AB  - Human intestinal infections with the nematode Strongyloides stercoralis remain a
      significant problem worldwide and a vaccine would be a useful addition to the
      tools available to prevent and control this infection. The goal of this study was
      to test single antigens for their efficacy in a vaccine against S. stercoralis
      larvae in mice. Alum was used as the adjuvant in these studies and antigens
      selected for analysis were either recognized by protective human IgG (Ss-TMY-1,
      Ss-EAT-6, and Ss-LEC-5) or were known to be highly immunogenic in humans (Ss-NIE
      1 and Ss-IR). Only mice immunized with the Ss-IR antigen demonstrated a
      significant decrease of approximately 80% in the survival of larval parasites in
      the challenge infection. Antibodies, recovered from mice with protective immunity
      to S. stercoralis after immunization with Ss-IR, were used to locate the antigen
      in the larvae. Confocal microscopy revealed that IgG from mice immunized with Ss
      IR bound to the surface of the parasites and observations by electron microscopy
      indicated that IgG bound to granules in the glandular esophagus. Serum collected
      from mice immunized with Ss-IR passively transferred immunity to naive mice.
      These studies demonstrate that Ss-IR, in combination with alum, induces high
      levels of protective immunity through an antibody dependent mechanism and may
      therefore be suitable for further development as a vaccine against human
      strongyloidiasis.

PMID- 21856351
TI  - Uptake of various yeast genera by antigen-presenting cells and influence of
      subcellular antigen localization on the activation of ovalbumin-specific CD8 T
      lymphocytes.
AB  - Yeasts of the genus Saccharomyces expressing recombinant antigens are currently
      evaluated as candidate T cell vaccines. Here, we compared the interaction
      kinetics between four biotechnologically relevant yeast genera (Saccharomyces
      cerevisiae, Schizosaccharomyces pombe, Kluyveromyces lactis and Pichia pastoris)
      and human dendritic cells as well as the involvement of Dectin-1 and mannose
      receptor in phagocytosis. Further, we analyzed the activation capacity of
      recombinant yeasts expressing ovalbumin (OVA) either intracellular, extracellular
      or surface-displayed by OVA-specific CD8 T lymphocytes. We found that the kinetic
      patterns of yeast uptake by phagocytic cells varied between the tested yeast
      genera and that both genus and subcellular OVA antigen localization influenced
      the strength of T cell activation. In particular, in S. cerevisiae, a secreted
      antigen was less effectively delivered than its cytosolic variant, whereas most
      efficient antigen delivery with P. pastoris was obtained by cell surface bound
      antigen. Our data indicate that protein secretion might not be an effective
      delivery pathway in yeast.

PMID- 21856352
TI  - Incorporation of immunostimulatory motifs in the transcribed region of a plasmid
      DNA vaccine enhances Th1 immune responses and therapeutic effect against
      Mycobacterium tuberculosis in mice.
AB  - T-helper type 1 (Th1) immune response is involved in the development of
      protective immunity against Mycobacterium tuberculosis. Thus, an increase in Th1
      and cellular immune responses should lead to enhanced anti-mycobacterial
      activity. In this study, we aimed to improve Th1 immune responses to a DNA
      vaccine by adding potentially immunostimulatory nucleotide sequences into the
      transcribed region downstream of the antigen. The Mycobacterium leprae gene for
      hsp65, codon-optimized for expression in mammalian cells, was inserted into pVAX1
      with and without 3'-sequences containing CpG and dsRNA motifs. When the plasmid
      contained both motifs, transfected murine macrophage-like RAW264.7 cells showed
      markedly increased levels of mRNA for immune molecules of Th1 (IFN-alpha, IL-12)
      and Th17 (IL-17, IL-23 and IL-6) responses and for T cell co-stimulatory
      molecules (CD80 and CD86) but not for a Th2 response (IL-4 and IL-10). Immunized
      mice showed substantially increased serum anti-Hsp65 IgG2a antibody levels and
      IFN-gamma production by spleen cells, confirming enhancement of the Th1 response
      in vivo. Furthermore, when non-vaccinated mice were infected with H37Rv by low
      dose aerosol challenge, and then 4 weeks later were treated with plasmids by
      intramuscular injection, the mice that had been treated with plasmids containing
      immunostimulatory motifs showed an enhanced reduction in mycobacterial loads in
      lung and spleen. We conclude that DNA vaccines may be made more highly
      immunogenic and more effective for treatment by including transcribed stimulatory
      sequences.

PMID- 21856353
TI  - Influence of maternal antibodies on active pertussis toxoid immunization of
      neonatal mice and piglets.
AB  - Whooping cough caused by infection with Bordetella pertussis, is a serious
      illness in infants and young children. Mortality due to whooping cough is being
      reported in infants too young to be immunized as well as those who have not
      completed their series of vaccinations. One of the major factors that interferes
      with successful active immunization in early life is the presence of maternal
      antibodies (MatAbs). Using the mouse and pig models, we evaluated the effect of
      maternal antibodies on active immunization with pertussis toxoid (PTd) and
      explored strategies to overcome this interference. Our results indicate that
      passively transferred maternal antibodies interfered with active immunization
      using pertussis toxoid. The level of passively transferred antibodies directly
      correlated with the level of interference observed. However, this interference
      could be overcome by using a second booster immunization or by co-formulating the
      toxoid with novel adjuvants. These results support the need for novel vaccine
      formulations that are optimized for the neonate and that can be used not only to
      modulate the inherently biased neonatal immune system but also to prime the
      response in the presence of passively transferred maternal antibodies.

PMID- 21856354
TI  - Foot-and-mouth disease marker vaccine: cattle protection with a partial VP1 G-H
      loop deleted virus antigen.
AB  - Contrary to the dogma that the VP1 G-H loop is essential for FMD vaccine
      efficacy, it has been previously shown that foot-and-mouth disease 146s antigen
      containing heterologous VP1 G-H loops confers complete protection in pigs and
      cattle. Moreover, serological evaluation of cattle vaccinated with an antigen
      lacking a large proportion of the VP1 G-H loop indicated that these animals
      should be protected against infection with FMD. Absence of this loop provides
      opportunity for the development of an FMD negative marker vaccine, allowing
      infection to be detected by antibodies against this missing region. Cattle
      vaccinated with this negative marker vaccine were fully protected following virus
      challenge 28 days post vaccination as determined by the absence of generalised
      lesions on their feet. Furthermore, use of our improved differentiation ELISA
      identified animals exposed to infection as early as 7 days post-challenge. We
      thus demonstrate, for the first time, the ability of this FMD negative marker
      vaccine to fully protect cattle from experimental challenge and rapidly
      distinguish animals that are subsequently exposed to infection.

PMID- 21856355
TI  - Recombinant Shiga toxin B subunit elicits protection against Shiga toxin via
      mixed Th type immune response in mice.
AB  - Shigella dysenteriae is the causative agent of the third commonest bacterial
      disease for childhood diarrhoea and responsible for millions of deaths per year.
      It produces potent toxin termed Shiga toxin which is listed in category B
      biological warfare agent of CDC, USA. Earlier we have reported production of
      recombinant Shiga toxin B subunit that produced antibodies which neutralized
      Shiga toxin toxicity in HeLa cells. In the present study, we have evaluated the
      immunomodulatory potential of rStxB protein in Balb/c mice using Freunds
      adjuvants. Animal protection with recombinant StxB was conferred through both
      humoral and cellular immune responses as indicated by an increased antibody titre
      with predominance of IgG2a and IgG2b isotypes along with elevated levels of IgG1
      subtype. Cytokine profile of the mice antiserum and splenocyte also indicates Th2
      and Th1 type of immune responses where former dominates in early stage of
      immunization. Histopathology study of kidneys of vaccinated mice showed
      remarkable differences when compared to the animals infected with Shigella
      dysenteriae type1. The present study indicates that recombinant StxB is a
      promising vaccine candidate and can be used for production of therapeutic
      antibodies to counter Shiga intoxication.

PMID- 21856358
TI  - Report of the 7th meeting on Evaluation of Pandemic Influenza Vaccines in
      Clinical Trials, World Health Organization, Geneva, 17-18 February 2011.
AB  - On February 17-18, 2011, the World Health Organization convened the 7th meeting
      on "The Evaluation of Pandemic Influenza Vaccines in Clinical Trials" to review
      the progress made on pandemic A (H1N1) 2009 vaccines and the evaluation of their
      effectiveness in the field, especially in children less than 3 years of age and
      in pregnant women. Other topics to be addressed included a comparison of egg- and
      cell culture-based influenza vaccines, technical issues related to vaccine strain
      development and vaccine potency, and the status of development of prototype
      influenza vaccines using new technologies. Pandemic A (H1N1) vaccines were safe
      in young children, pregnant women and immunocompromized individuals. Overall
      effectiveness of inactivated A (H1N1) vaccines for all ages was found to vary
      between 72% and 100% in different countries and with different vaccine
      preparations. Effectiveness of pandemic A (H1N1) 2009 live attenuated vaccine was
      estimated to be approximately 80% in pediatric populations in the USA. A single
      dose of inactivated vaccine adjuvanted with AS03, MF59 or AF03 induced protective
      immunity in young children and pregnant women. However, unadjuvanted vaccines as
      well as low dose adjuvanted vaccines (1.9 MUg HA) required two doses to elicit
      protective antibody levels in these populations. Clinical trials of influenza
      vaccines developed using new technologies showed they were well tolerated and
      induced antibody and/or T cell immune responses to viral proteins. Further
      studies are warranted to validate novel immunological criteria for evaluation and
      licensing of such new influenza vaccine concepts. On the regulatory side, work
      should be undertaken to harmonize the results of serological tests used to
      evaluate the immunogenicity of traditional influenza vaccines.

PMID- 21856357
TI  - Immunization with recombinant Lactobacillus casei strains producing K99, K88
      fimbrial protein protects mice against enterotoxigenic Escherichia coli.
AB  - To exploit a safe and effective vaccine for the prevention against K99 or K88
      infections of enterotoxigenic Escherichia coli (ETEC), we have developed a
      mucosal delivery vehicle based on Lactobacillus casei CICC 6105 using poly-gamma
      glutamate synthetase A (PgsA) as an anchoring matrix. To evaluate the
      immunization effect of the recombinant strains (harboring plasmids pLA-K99-K88
      LTB, pLA-K99, and pLA-K88), anti-ETEC K99 or K88 antibody responses, T-cell
      proliferation, and cytokines by intracellular staining (ICS) were investigated
      after specific pathogen-free (SPF) C57BL/6 mice orally inoculated with these
      recombinant strains. After oral vaccination into C57BL/6 mice, all recombinant
      strains were proved to be immunogenic and able to elicit high levels of mucosal
      immunoglobulin A (IgA) titers in bronchoalveolar lavage fluids, intestinal fluids
      and prominent systemic immunoglobulin G and IgG subclasses (IgG1, IgG2b, and
      IgG2a) responses in sera. Using the T-cell proliferation assay, the stimulation
      index (SI) of groups immunized with pLA-K99/L. casei and pLA-K88/L. casei reached
      to 2.73 and 2.64, respectively, versus 2.56 in a group immunized with pLA-K99-K88
      LTB/L. casei. A detailed analysis of the cell-mediated immune responses by ICS
      showed the number of specific CD8(+) T cells expressing cytokines (IFN-gamma, TNF
      alpha, and IL-2) and granule-associated proteins (CD107a) was higher than that of
      specific CD4(+) T cells secreted by immune spleen cells upon restimulation in
      vitro with peptides. Next, the results showed that DCs activated in vitro with
      recombinant L. casei enhance specific T-cell proliferation and promote T cells to
      produce both Th1 and Th2 cytokines. More than 80% of the vaccinated mice were
      protected after challenge with a lethal dose of standard strains C83912 and
      C83902. These results demonstrate that recombinant L. casei can induce specific
      humoral and mucosal antibodies and cellular immune response against protective
      antigens upon oral administration.

PMID- 21856359
TI  - Rotavirus shedding in premature infants following first immunization.
AB  - OBJECTIVE: There is limited data regarding rotavirus vaccine shedding in
      premature infants. We describe the natural history of rotavirus shedding in
      premature infants in the 2-week period following first immunization with
      RotaTeq((r)), the pentavalent rotavirus vaccine (RV5), and the risk for
      symptomatic transmission to household contacts (HHC). PATIENTS AND METHODS: A
      prospective pilot study of 15 premature infants of gestational ages 26-34 weeks
      immunized with RV5 between 6 and 14 weeks chronological age on discharge from the
      NICU was conducted. Stool samples collected in the following 2 weeks and analyzed
      for rotavirus antigen by enzyme immunoassay (EIA), cell culture, and RT-PCR.
      Solicited adverse events were collected on study subjects and any symptoms of
      fever, vomiting and diarrhea in HHC. RESULTS: Rotavirus antigen shedding after
      immunization was detected, with positive rotavirus EIA results in 53.3% of
      premature infants and in 22.1% of 86 stool samples collected. Shedding rates by
      RT-PCR were higher with 86.7% of infants and 76.7% of samples being positive.
      Only 42% of EIA positive samples were positive by cell culture (8/86 total
      samples, 9.3%). None of 53 HHC reported symptoms of rotavirus infection during
      the 4 weeks following immunization of the infants. CONCLUSIONS: The findings of
      this study demonstrate that premature infants have positive stools by EIA, viral
      culture, and RT-PCR at varying time points during 2 weeks following first-dose
      immunization with RV5. RT-PCR shedding rates need to be clinically evaluated in
      the context of virus quantification by cell culture, which was low. No
      symptomatic transmission to HHC was detected in this study, supporting low
      transmissibility of vaccine virus shed by these infants born prematurely.

PMID- 21856360
TI  - Like mother, like daughter? Mother's history of cervical cancer screening and
      daughter's Human Papillomavirus vaccine uptake in Flanders (Belgium).
AB  - OBJECTIVE: We investigated whether and to what extent the uptake of the Human
      Papillomavirus (HPV) vaccine by girls aged 12-18 was related to the cervical
      cancer screening history of age-appropriate older female household members
      (assumed to be their mothers) in Flanders (Belgium). METHODS: We studied
      administrative records on 127,854 female members of the National Alliance of
      Christian Mutualities, which is the largest health insurance fund in Flanders.
      Reimbursement data for HPV vaccination of girls for the period 2007-2009 were
      linked with reimbursement data for cervical cancer screening of their mothers in
      the three preceding years. A multilevel logit model was used to study
      associations between both preventive behaviors. In the model we controlled for
      both the girl's and the mother's age, the province of residence and the socio
      economic background of the family. RESULTS: A clear association between a
      mother's history of participation in cervical cancer screening and her daughter's
      HPV vaccination initiation was found. The conditional odds of HPV vaccination
      initiation were more than 4 times higher for girls whose mother had one Pap test
      than for girls whose mother had none (odds ratio [OR]=4.5; 95% confidence
      interval [CI]=3.5-5.9). For girls whose mother had three or more Pap tests, the
      conditional odds were 16 times higher than for girls whose mother did not have
      any pap tests ([OR]=16.0; 95% [CI]=12.1-21.2). The effect of screening (having
      received 1 pap smear as compared to none) was larger for girls living in
      neighborhoods with the lowest median income ([OR]=6.0, 95% [CI]=3.6-10.1).
      CONCLUSION: In a situation where both cervical cancer screening and HPV
      vaccination are opportunistic, we found evidence that these preventive behaviors
      cluster within families.

PMID- 21856361
TI  - Over-expression of superoxide dismutase obliterates the protective effect of BCG
      against tuberculosis by modulating innate and adaptive immune responses.
AB  - An efficient global control of tuberculosis requires development of alternative
      vaccination strategies that can enhance the efficacy of existing BCG vaccine. In
      this study, we evaluated the protective efficacy of a recombinant BCG (rBCG)
      vaccine over-expressing iron-cofactored superoxide dismutase (SOD-A), one of the
      prominent oxidative stress response proteins of Mycobacterium tuberculosis.
      Contrary to our expectations, over-expression of SOD-A resulted in the abrogation
      of BCG's ability to confer protection in guinea pig as well as in murine model.
      Analysis of immune responses revealed that over-expression of SOD-A by rBCG has
      pleiotropic effects on innate and adaptive immune responses. Macrophages infected
      in vitro with rBCG exhibited a marked reduction in apoptosis and microbicidal
      potential. In addition, rBCG vaccination of mice resulted in a reduced IFNgamma
      and increased IL10 production when compared with the BCG vaccination. Further, we
      show that rBCG vaccination failed to generate an effective multi-functional CD4 T
      cell response. Altogether, our findings suggest that over-expression of SOD-A in
      BCG enhances the immuno-suppressive properties of BCG, characterized by skewing
      of immune responses towards Th2 type, an inefficient multi-functional T cell
      response and reduced apoptosis and microbicidal potential of macrophages leading
      to abolishment of BCG's protective efficacy.

PMID- 21856362
TI  - Are medical residents a "core group" for future improvement of influenza
      vaccination coverage in health-care workers? A study among medical residents at
      the University Hospital of Palermo (Sicily).
AB  - Despite international recommendations, vaccination coverage among European
      healthcare workers, including physicians, is widely recognized as unsatisfactory.
      In order to plan tailored vaccination campaigns and increase future coverage, we
      investigated reasons for refusing vaccination and determinants associated with
      influenza vaccine uptake among young health care workers. A survey was carried
      out during September and October 2010 on medical residents attending post
      graduate Schools of the Medical Faculty at the University of Palermo (Italy).
      Each participant completed an anonymous web-based questionnaire including items
      on demographic and occupational characteristics, knowledge, attitudes and
      behaviours with regard to influenza and influenza vaccination, and main sources
      of information. A total of 202 (66.9%) out of 302 medical residents participated
      in the survey. During the 2009-2010 influenza vaccine campaign, 44 residents
      (21.8%) were vaccinated against seasonal influenza and 84 (41.6%) against
      pandemic influenza A (H1N1) 2009. For the impending 2010-2011 influenza season,
      45 (22.3%) stated their intention to get vaccinated against seasonal influenza,
      40 (19.8%) were uncertain and 117 (57.9%) were opposed. Considering themselves to
      be a high risk group for developing influenza was significantly associated with
      vaccination against both 2009-2010 seasonal (adj-OR=1.46; 95% CI=1.05-2.04) and
      pandemic A (H1N1) influenza (adj-OR 1.38; 95% CI=1.08-1.75). Intention to get
      vaccinated against 2010-2011 seasonal influenza was significantly more frequent
      in participants who had a high perception of efficacy/safety (adj-OR=1.49; 95%
      CI=1.05-2.12). After adjusting for confounding, vaccinations against seasonal
      2009-2010 influenza, pandemic influenza A (H1N1) 2009 and seasonal 2010-2011
      influenza were significantly more frequent in residents who were vaccinated
      against influenza at least once in the previous five influenza seasons. Influenza
      vaccination among medical residents appears to be habitual, with little
      comprehension of the rationale and logic for vaccination, including the need to
      be vaccinated to protect patients from nosocomial influenza infection. Our study
      suggests the importance of prioritizing residents for vaccination campaigns, as
      they represent "the future" and include a core group that habitually accepts
      vaccination.

PMID- 21856363
TI  - Dentists' awareness toward vaccine preventable diseases.
AB  - Effective infection control in dentistry is unfeasible without an adequate
      immunization program for dental health care providers (DHCPs). Such an assumption
      is demonstrated for some vaccine preventable infectious diseases (VPIDs), such as
      Hepatitis B, Influenza and Varicella. However, excluding Hepatitis B vaccine,
      immunization programs for DHCPs are few and often unclear about which
      vaccinations are recommended, thus leading to generally low awareness and
      consequent low vaccination rates. This survey investigated dentists' awareness
      toward VPIDs. At the moment of registration to a dental congress, a questionnaire
      regarding the immunization status toward VPIDs was anonymously filled in by 379
      Italian dentists (86% of the contacted dentists), with at least fifteen years of
      activity. DHCP specific awareness was considered high if dentists reported to
      have controlled the serum level of anti-HBs during the last ten years and have
      received seasonal influenza vaccine annually. Awareness toward VPIDs was
      classified high if dentists reported to be immune against six or seven of the
      following VIPDs, Hepatitis B, Influenza, Varicella, Measles, Mumps, Rubella and
      Tetanus. DHCP specific awareness resulted high for 32.5% of subjects and low for
      31.1%. None of the subjects reported high awareness toward VPIDs, while for 60%
      of them, such awareness was low (immunization status reported for none or one of
      the seven VPIDs). Low dentists' awareness stresses the need for a transparent
      immunization program which is effective in controlling VPID transmission in the
      dental health care settings and focuses on those VPIDs which pose a true risk of
      infection for DHCPs and patients.

PMID- 21856364
TI  - Preclinical toxicity of DATR, a recombinant soluble human TRAIL mutant, in rats
      and cynomolgus monkeys.
AB  - The recombinant soluble human TRAIL mutant (DATR), derived from tumour necrosis
      factor-related apoptosis-inducing ligand (TRAIL), is a promising agent for cancer
      therapy. The present study evaluated the toxicity of DATR in rats and monkeys.
      Based on the results, the safety and toxic doses of DATR intravenously injected
      to rats for 50 days were 60 and 180 mg/kg, respectively, and when delivered
      intravenously guttae to monkeys for 50 days, these levels were 10 and 30 mg/kg,
      respectively. The main toxic effects in rats were red blood cell count and
      haemoglobin decreases; blood urea nitrogen and creatinine increases. The main
      toxic effects in monkeys included red blood cell count and haemoglobin decreases;
      alanine aminotransferase and aspartate aminotransferase increases; high
      proliferation of karyocytes of the erythrocyte series; and regional hydropic
      degeneration of hepatic parenchymal cells. The TUNEL assay showed both 90 mg/kg
      DATR- and TRAIL-induced apoptosis of the liver in monkeys, which confirmed the
      hepatotoxicity of DATR. These findings indicated that the target toxic organs of
      DATR might be the haematological system. Furthermore, kidney in rats and liver in
      monkeys are also likely target toxic organs. The toxicity was reversible and did
      not differ from that associated with TRAIL administered at the same dosage.

PMID- 21856365
TI  - Bioaccessibility of Hg, Cd and As in cooked black scabbard fish and edible crab.
AB  - Regular consumption of seafood has been widely recommended by authorities. Yet,
      some species accumulate high levels of contaminants like Hg, Cd and As. In
      addition, the risks associated to the consumption of such seafood may increase if
      consumers use cooking practices that enhance the concentration of contaminants
      and their bioaccessibility. In this study, the bioaccessibility of Hg, Cd and As
      was assessed with in vitro human digestion of raw and cooked black scabbard fish
      (Hg; steamed, fried and grilled) and edible crab (Cd and As; steamed and boiled)
      tissues. Additionally, the toxicological hazards associated with the consumption
      of these products were also discussed. Generally, Hg, Cd and As bioacessibility
      increased throughout the digestion process. Cadmium and As revealed high
      bioaccessibility rates in raw and cooked samples (up to 100%), whereas lower
      bioaccessible fractions of Hg was observed (up to 40%). Furthermore, this study
      pointed out the importance of food matrix, elemental chemical properties and
      cooking practices in the bioaccessibility of Hg, Cd and As. The toxicological
      hazards revealed that edible crab brown meat (Cd) and grilled black scabbard fish
      (MeHg) consumption in children should be moderated. In contrast, edible crab
      muscle (Cd) and fried or steamed black scabbard fish (MeHg) should be consumed to
      minimize exposure. The use of bioaccessible contaminant data strongly reduced the
      toxicological risks of MeHg, whereas less risk reduction occurred with Cd and
      inorganic As.

PMID- 21856366
TI  - Safety assessment of mushroom beta-glucan: subchronic toxicity in rodents and
      mutagenicity studies.
AB  - Mushroom beta-glucan, a polymer of beta-(1,3/1,6)-glucan, has been claimed for
      its health benefits. The objective of this study was to assess the safety in-use
      of mushroom beta-glucan as dietary supplement and food ingredient. Hence, a
      subchronic toxicity and mutagenicity studies were conducted. In the subchronic
      toxicity study, Sprague Dawley rats (12/sex/group) were administered (gavage)
      mushroom beta-glucan at dose levels of 0, 500, 1000 and 2000 mg/kg body weight
      (bw)/day for 90 days. As compared to control group, administration of beta-glucan
      did not result in any toxicologically significant treatment-related changes in
      clinical observations, ophthalmic examinations, body weights, body weight gains,
      feed consumption, and organ weights. No adverse effects of the beta-glucan on the
      hematology, serum chemistry parameters, urinalysis or terminal necropsy (gross or
      histopathology findings) were noted. The results of mutagenicity studies as
      evaluated by gene mutations in Salmonella typhimurium, in vitro chromosome
      aberrations and in vivo micronucleus test in mouse did not reveal any
      genotoxicity of beta-glucan. Based on the subchronic study, the no observed
      adverse-effect level (NOAEL) for mushroom beta-glucan was determined as 2000
      mg/kgbw/day, the highest dose tested.

PMID- 21856367
TI  - Effects of acidulated phosphate fluoride gel application on surface roughness,
      gloss and colour of different type resin composites.
AB  - OBJECTIVE: Application of acidulated phosphate fluoride (APF) gel has been
      reported to cause deterioration of resin composites. This study investigated the
      effects of APF gel application on surface roughness, gloss and colour of resin
      composites. METHODS: A2-shade resin disks of 2mm thickness polished with 180-grit
      and 3000-grit SiC papers were made with Estelite Sigma Quick (EQ), Clearfil
      Majesty (CM) and Beautifil II (B2). Six disks were prepared for each group. APF
      gel was applied in a 3mm thickness on the top surface of resin disks and left for
      30min followed by rinsing and ultrasonic washing. This procedure was repeated 4
      times. The L*a*b* values, colour difference (DeltaE*ab), opacity, surface gloss
      and roughness of specimens before and after APF application were compared. Data
      were analysed ANOVA and Fisher's PLSD test with alpha=0.05. RESULTS: For the 3000
      grit polishing groups, the order of influence of APF gel application on colour of
      resin composites was CM>B2>EQ. Both in the 180- and 3000-grit polishing groups,
      colour difference before and after APF gel application was hard to detect (CM and
      B2) or impossible to detect (EQ) by naked eye. On the other hand, for all the
      resin composites, the gloss was significantly decreased by APF gel application.
      APF gel appeared to cause deterioration and dissolution of resin composites used
      in this study. SIGNIFICANCE: In this limited study, supra-nano spherical filled
      Estelite Sigma Quick showed the least change on colour, gloss and surface
      roughness by APF gel application.

PMID- 21856368
TI  - The effect of low intensity pulsed ultrasound in a 3D ex vivo orthodontic model.
AB  - OBJECTIVES: This study investigated the effects of low intensity pulsed
      ultrasound (LIPUS) on dentoalveolar structures during orthodontic force
      application using a novel organ culture system. METHODS: Mandibles were dissected
      from 28-day-old male Sprague Dawley rats, sliced into 1.5mm and cultured at 37
      degrees C and 5% CO(2), prior to application of a 50g force to each mandible
      slice. Slices were randomly divided into three groups of control, 5 and 10min
      LIPUS application and cultured for five days before histological and
      histomorphometrical analysis. RESULTS: Cementum and predentine thickness and
      subodontoblast and periodontal ligament cell counts were increased in the
      ultrasound groups, with increases statistically significant in the 10min treated
      groups. Odontoblasts remained viable during LIPUS exposure and osteoclast
      activity was increased by LIPUS. CONCLUSIONS: LIPUS may influence remodelling of
      the dentine-pulp complex and associated tissues during orthodontic force
      application ex vivo.

PMID- 21856369
TI  - The effects of titanium nitride-coating on the topographic and biological
      features of TPS implant surfaces.
AB  - OBJECTIVES: Titanium nitride (TiN) coating has been proposed as an adjunctive
      surface treatment aimed to increase the physico-mechanical and aesthetic
      properties of dental implants. In this study we investigated the surface
      characteristics of TiN-coated titanium plasma sprayed (TiN-TPS) and uncoated
      titanium plasma sprayed (TPS) surfaces and their biological features towards both
      primary human bone marrow mesenchymal stem cells (BM-MSC) and bacterial cultures.
      METHODS: 15 mm*1 mm TPS and TiN-TPS disks (P.H.I. s.r.l., San Vittore Olona,
      Milano, Italy) were topographically analysed by confocal optical profilometry.
      Primary human BM-MSC were obtained from healthy donors, isolated and expanded.
      Cells were seeded on the titanium disks and cell adhesion, proliferation, protein
      synthesis and osteoblastic differentiation in terms of alkaline phosphatase
      activity, osteocalcin synthesis and extracellular mineralization, were evaluated.
      Furthermore, adhesion and proliferation of Streptococcus pyogenes and
      Streptococcus sanguinis on both surfaces were also analysed. RESULTS: TiN-TPS
      disks showed a decreased roughness (about 50%, p < 0.05) and a decreased
      bacterial adhesion and proliferation compared to TPS ones. No difference (p >
      0.05) in terms of BM-MSC adhesion, proliferation and osteoblastic differentiation
      between TPS and TiN-TPS surfaces was found. CONCLUSIONS: TiN coating showed to
      modify the topographical characteristics of TPS titanium surfaces and to
      significantly reduce bacterial adhesion and proliferation, although maintaining
      their biological affinity towards bone cell precursors.

PMID- 21856370
TI  - Human liver fatty acid binding protein (hFABP1) gene is regulated by liver
      enriched transcription factors HNF3beta and C/EBPalpha.
AB  - The human liver fatty acid binding protein (hFABP1) participates in cellular long
      chain fatty acid trafficking and regulation of lipid metabolism and changes in
      hFABP1 are associated with an increased risk for type 2 diabetes, cardiovascular
      disease (CVD), and metabolic syndromes. Gene regulation of hFABP1 is not fully
      understood. Therefore, in the present study, the full length hFABP1 promoter
      (nucleotides -2125 to +51) and a series of truncated promoter regions were
      cloned. A luciferase reporter assay revealed that nucleotides -255 to +50 in the
      promoter region contained full of maximum hFABP1 promoter activity compared with
      the full length promoter. Furthermore high activity was shown when the plasmid
      was transfected into liver-derived cells such as the human hepatoblastoma cell
      line HepG2 and the hepatoma cell line Huh7. TFSEARCH and TESS programs were used
      to predict potential transcription factor binding sites. Two putative binding
      sites for the liver-enriched transcription factors hepatocyte nuclear factor
      3beta (HNF3beta) and CCAAT/enhancer binding protein alpha (C/EBPalpha) were
      identified in the -255 nt to -155 nt hFABP1 promoter region. Site-directed
      mutagenesis of these two sites reduced dramatically hFABP1 promoter activity. In
      addition, the electrophoretic mobility shift assay (EMSA) and chromatin
      immunoprecipitation assay (ChIP) revealed that these binding sites were
      recognized by HNF3beta and C/EBPalpha respectively. Overexpression of HNF3beta
      and C/EBPalpha enhanced the transcription of hFABP1 and consequently improved the
      protein level of hFABP1 in HepG2 cells, while knockdown of HNF3beta and
      C/EBPalpha showed the inverse effects. Taken together, the hFABP1 gene is highly
      transcribed in liver-derived cells, and regulated predominantly by liver-enriched
      transcription factors HNF3beta and C/EBPalpha.

PMID- 21856371
TI  - Caffeine inhibits erythrocyte membrane derangement by antioxidant activity and by
      blocking caspase 3 activation.
AB  - The aim of this research was to investigate the effect of caffeine on band 3 (the
      anion exchanger protein), haemoglobin function, caspase 3 activation and glucose
      6-phosphate metabolism during the oxygenation-deoxygenation cycle in human red
      blood cells. A particular attention has been given to the antioxidant activity by
      using in vitro antioxidant models. Caffeine crosses the erythrocyte membrane and
      interacts with the two extreme conformational states of haemoglobin (the T and
      the R-state within the framework of the simple two states allosteric model) with
      different binding affinities. By promoting the high affinity state (R-state), the
      caffeine-haemoglobin interaction does enhance the pentose phosphate pathway. This
      is of benefit for red blood cells since it leads to an increase of NADPH
      availability. Moreover, caffeine effect on band 3, mediated by haemoglobin,
      results in an extreme increase of the anion exchange, particularly in oxygenated
      erythrocytes. This enhances the transport of the endogenously produced CO(2)
      thereby avoiding the production of dangerous secondary radicals (carbonate and
      nitrogen dioxide) which are harmful to the cellular membrane. Furthermore
      caffeine destabilizes the haeme-protein interactions within the haemoglobin
      molecule and triggers the production of superoxide and met-haemoglobin. However
      this damaging effect is almost balanced by the surprising scavenger action of the
      alkaloid with respect to the hydroxyl radical. These experimental findings are
      supported by in silico docking and molecular dynamics studies and by what we may
      call the "caspase silence"; in fact, there is no evidence of any caspase 3
      activity enhancement; this is likely due to the promotion of positive metabolic
      conditions which result in an increase of the cellular reducing power.

PMID- 21856372
TI  - 1/f(p) Characteristics of the Fourier power spectrum affects ERP correlates of
      face learning and recognition.
AB  - We investigated the influence of Fourier power spectrum (1/f(p)) characteristics
      on face learning while recording ERPs that are associated with the representation
      of faces. Two image sets with an altered 1/f(p) characteristics were created. The
      first set consisted of stimuli with a STEEP SLOPE (1/f(3.5)) and therefore
      enhanced low spatial frequencies (LSF) and attenuated high spatial frequencies
      (HSF). The second set consisted of stimuli with a SHALLOW SLOPE (1/f(2)), similar
      to complex natural scenes and artwork, resulting in enhanced HSF and attenuated
      LSF. Faces with a SHALLOW SLOPE elicited larger N170 and N250 amplitudes and
      larger old/new effects for central positivity in comparison to unmodified faces.
      The opposite effect was observed for faces with a STEEP SLOPE that led to slower
      reaction times. This result suggests that diminishing the ratio of fine detail
      (HSF) to coarse structures (LSF) impairs face learning, whereas increasing it
      facilitates neurocognitive correlates of face learning.

PMID- 21856373
TI  - Heart rate variability in response to affective scenes in posttraumatic stress
      disorder.
AB  - Posttraumatic stress disorder (PTSD) is characterized by psychophysiological
      abnormalities, such as an altered baseline heart rate and either hyper- or
      hyporeactivity to a wide range of stimuli, implying dysfunctional arousal
      regulation. Heart rate variability (HRV) has been established as an important
      marker of arousal regulatory ability. The aim of the present study was to examine
      HRV in PTSD under different affective conditions and to explore the role of
      potential moderating factors. To meet this purpose, videos of varying emotional
      valence were presented to trauma-exposed participants with PTSD (n=26), trauma
      exposed participants without PTSD (n=26), as well as non-trauma-exposed controls
      (n=18) while HRV was recorded. The PTSD group showed lower HRV than non-trauma
      exposed controls at baseline (corrected for age) and throughout different
      affective conditions implying decreased parasympathetic activity and an
      inflexible response regulation. There was a negative relationship between HRV and
      self-report of both depression and state dissociation.

PMID- 21856374
TI  - Oogenesis: transcriptional regulators and mouse models.
AB  - Oocyte differentiation into a totipotent cell requires initial germ cell cyst
      breakdown to form primordial follicles, recruitment of primordial follicles for
      development into primary follicles and remarkable growth of the ovarian follicle
      which culminates in ovulation. During oogenesis, the oocyte undergoes dynamic
      alterations in gene expression which are regulated by a set of well-coordinated
      transcription factors active in the germ line and soma. A number of germ cell
      specific as well as somatic expressed transcriptional regulators are critical in
      ovarian formation and folliculogenesis. These transcriptional regulators include:
      Foxo3, Foxl2, Figla, Lhx8, Nobox, Sohlh1 and Sohlh2. A subset of these
      transcriptional regulators is mutated in women with ovarian insufficiency and
      infertility. Studies on transcriptional regulators preferentially expressed in
      the ovary are important to develop a better understanding of the mechanisms of
      activation and survival of ovarian follicles, as well as an understanding of
      ovary specific pathways that can be modulated in the future to regulate fertility
      and protect against external insults such as chemotherapy.

PMID- 21856375
TI  - The role of CHD7 and the newly identified WDR11 gene in patients with idiopathic
      hypogonadotropic hypogonadism and Kallmann syndrome.
AB  - Mutations in the chromodomain helicase DNA binding protein-7 (CHD7) cause CHARGE
      syndrome, which includes eye coloboma, heart malformations, atresia of the
      choanae, retardation of growth/development, genital anomalies, and ear
      abnormalities. CHARGE syndrome is usually sporadic, but is also autosomal
      dominant. CHD7 encodes a large protein that participates in chromatin remodeling
      and transcription. Findings from studies of mouse models employing ENU
      mutagenesis or gene-trap methods recapitulate human CHARGE syndrome. CHARGE
      patients may manifest anosmia and/or hypogonadism, features that overlap with
      idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS).
      Similarly, IHH/KS patients may also display partial CHARGE features. Therefore,
      it has been hypothesized that IHH/KS represents a milder allelic variant of
      CHARGE syndrome, which has been supported by the identification of heterozygous
      CHD7 mutations in both normosmic IHH and KS. Developmental expression within the
      hypothalamus and the presence of human mutations indicate that CHD7 has an
      important role in puberty and reproduction. In addition, WDR11 was recently
      identified by positional cloning; and mutations in were identified in IHH/KS
      patients, suggesting a role for this gene in normal puberty.

PMID- 21856376
TI  - Differential modulation of apoptotic gene expression by N-acetyl-L-cysteine in
      Leydig cells stimulated persistently with hCG in vivo.
AB  - The present study was designed to investigate the molecular mechanisms of NAC
      (150 mg/kg bw twice/week) action in vivo under repeated hCG (100 IU/rat/day)
      stimulation to adult rats. Leydig cell refractoriness led to a significant
      decline in serum testosterone and intracellular cAMP by day 30 of chronic hCG
      intervention which improved significantly following NAC co-administration. It
      inhibited the rise in lipid peroxidation, improved the activity of antioxidant
      enzymes along with intracellular glutathione and total antioxidant capacity in
      the target cells. Leydig cell apoptosis declined significantly (P<0.001) with
      down-regulation of upstream, Fas, FasL, caspase-8, Bax and caspase-9, JNK/pJNK
      and downstream caspase-3 and PARP. On the other hand, anti-apoptotic Bcl2, NF
      kbeta, and Akt were up-regulated. Taken together, the above findings indicate
      that the specificity of NAC action was not restricted to regulating marker
      proteins in the extrinsic and JNK pathways as seen in vitro but extended to
      include intrinsic pathway of metazoan apoptosis as well.

PMID- 21856377
TI  - Activation of caspase-3 and c-Jun NH2-terminal kinase signaling pathways
      involving heroin-induced neuronal apoptosis.
AB  - Heroin has been shown to cause spongiform leukoencephalopathy (SLE) in heroin
      addicts. In this study, we found that heroin could induce apoptosis of primary
      cultured cerebellar granule cells (CGC) and c-Jun N-terminal kinase (JNK) pathway
      is activated during CGCs apoptosis. Inhibiting JNK with a specific inhibitor,
      SP600125, reduced the levels of c-Jun phosphorylation and caspase-3 activation.
      We also showed that use the JNK inhibitor SP600125, caspase inhibitor z-VAD, or
      use SP600125 and z-VAD together significantly suppressed cell death induced by
      heroin. These results indicate that JNK pathway is an important mediator of the
      neurotoxic effects of heroin and inhibiting JNK activity may represent a new and
      effective strategy to treat heroin-induced SLE.

PMID- 21856379
TI  - Overexpression of TFAM, NRF-1 and myr-AKT protects the MPP(+)-induced
      mitochondrial dysfunctions in neuronal cells.
AB  - BACKGROUND: Mitochondrial dysfunction is a prominent feature of neurodegenerative
      diseases including Parkinson's disease (PD), in which insulin signaling pathway
      may also be implicated because 50-80% of PD patients exhibited metabolic syndrome
      and insulin resistance. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and
      its toxic metabolite, 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPP(+)),
      inhibit complex I in mitochondrial respiratory chain and are used widely to
      construct the PD models. But the precise molecular link between mitochondrial
      damage and insulin signaling remains unclear. METHODS AND RESULTS: Using cell
      based mitochondrial activity profiling system, we systemically demonstrated that
      MPP(+) suppressed mitochondrial activity and mitochondrial gene expressions
      mediated by nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription
      factor A (TFAM) in SH-SY5Y cells. MPP(+) fragmented mitochondrial networks and
      repressed phosphorylation of AKT. Similarly, the expressions of mitochondrial
      genes and tyrosine hydroxylase and AKT phosphorylation were reduced in substantia
      nigra and striatum of MPTP-injected mice. Transient transfection of TFAM, NRF-1,
      or myr-AKT reversed all aspects of the MPP(+)-mediated changes. CONCLUSIONS:
      Mitochondrial activation by TFAM, NRF-1, and myr-AKT abrogated MPP(+)-mediated
      damages on mitochondria and insulin signaling, leading to recovery of
      nigrostriatal neurodegeneration. GENERAL SIGNIFICANCE: We suggest that TFAM, NRF
      1, and AKT may be the critical points of therapeutic intervention for PD. This
      article is part of a Special Issue entitled Biochemistry of Mitochondria.

PMID- 21856380
TI  - Inhibitory descending rhombencephalic projections in larval sea lamprey.
AB  - Lampreys are jawless vertebrates, the most basal group of extant vertebrates.
      This phylogenetic position makes them invaluable models in comparative studies of
      the vertebrate central nervous system. Lampreys have been used as vertebrate
      models to study the neuronal circuits underlying locomotion control and axonal
      regeneration after spinal cord injury. Inhibitory inputs are key elements in the
      networks controlling locomotor behaviour, but very little is known about the
      descending inhibitory projections in lampreys. The aim of this study was to
      investigate the presence of brain-spinal descending inhibitory pathways in larval
      stages of the sea lamprey Petromyzon marinus by means of tract-tracing with
      neurobiotin, combined with immunofluorescence triple-labeling methods.
      Neurobiotin was applied in the rostral spinal cord at the level of the third
      gill, and inhibitory populations were identified by the use of cocktails of
      antibodies raised against glycine and GABA. Glycine-immunoreactive (-ir) neurons
      that project to the spinal cord were observed in three rhombencephalic reticular
      nuclei: anterior, middle and posterior. Spinal-projecting GABA-ir neurons were
      observed in the anterior and posterior reticular nuclei. Double glycine-ir/GABA
      ir spinal cord-projecting neurons were only observed in the posterior reticular
      nucleus, and most glycine-ir neurons did not display GABA immunoreactivity. The
      present results reveal the existence of inhibitory descending projections from
      brainstem reticular neurons to the spinal cord, which were analyzed in
      comparative and functional contexts. Further studies should investigate which
      spinal cord circuits are affected by these descending inhibitory projections.

PMID- 21856382
TI  - Transcriptome analysis in mitochondrial disorders.
AB  - The spectrum of genetic disorders associated with primary mitochondrial
      dysfunction ranges from isolated hearing loss to lethal neonatal syndromes.
      Mitochondrial biogenesis and function relies on the enigmatic interplay of the
      mitochondrial and nuclear genome and allows for adjustment of energy consumption
      to substrate availability and adaption to genetic and toxic stressors. Whole
      transcriptome studies permit a global perspective on these events and promise
      deeper insight into mitochondrial physiology and dysfunction. Data coming from
      microarray studies has revealed the activation of an intricate signaling network
      that promotes bioenergetic adaption through autophagy and enhanced mitochondrial
      biogenesis. The effectors of this network are currently under much investigation
      for their therapeutic potential. Microarray data also implicate a profound impact
      of mitochondrial dysfunction on global nuclear transcription activity through
      alteration of genomic stability, cell cycle progression and epigenetic
      regulation. In this review, results of gene expression studies performed on human
      and animal tissue as well as cell culture models with mitochondrial dysfunction
      are summarized and discussed.

PMID- 21856381
TI  - Reduction of high-fat diet-induced obesity after chronic administration of brain
      derived neurotrophic factor in the hypothalamic ventromedial nucleus.
AB  - An acute injection of brain-derived neurotrophic factor (BDNF) in the
      hypothalamic ventromedial nucleus (VMN) decreases body weight by reducing feeding
      and increasing energy expenditure (EE) in animals on standard laboratory chow.
      Animals have divergent responses to high-fat diet (HFD) exposure, with some
      developing obesity and others remaining lean. In the current study, we tested the
      hypothesis that BDNF in the VMN reduces HFD-induced obesity. Seventy-two 10-week
      old rats were allowed HFD ad libitum for 8 weeks and then prepared with bilateral
      VMN cannulae. Animals were then divided into tertiles based on their fat mass
      rank: high, intermediate, and low (H, I, and L). Each group was further divided
      into two subgroups: BDNF (1 MUg) or control (artificial cerebrospinal fluid,
      aCSF); they were then injected every other day for 20 days according to subgroup.
      Energy intake, body weight, and body composition were measured. Other metabolic
      indexes were measured before and after treatment. In parallel, another 12 rats
      were fed control diet (CD), VMN-cannulated, and injected with aCSF. HFD exposure
      induced obesity in the H group, with a significant increase in energy intake,
      body weight, fat mass, liver size, and serum glucose, insulin, and leptin. BDNF
      significantly reduced body weight and fat mass in all phenotypes, while it
      reduced energy intake only in the I group. However, BDNF increased EE,
      spontaneous physical activity, and fat oxidation in the H group, suggesting that
      BDNF-induced EE elevation contributed to reduction of body weight and fat mass.
      Chronic VMN BDNF reduced insulin elevation and/or reversed hyperleptinemia. These
      data suggest that the VMN is an important site of action for BDNF reduction of
      HFD-induced obesity.

PMID- 21856383
TI  - Increased 3-nitrotyrosine levels in mitochondrial membranes and impaired
      respiratory chain activity in brain regions of adult female rats submitted to
      daily vitamin A supplementation for 2 months.
AB  - Vitamin A supplementation among women is a common habit worldwide in an attempt
      to slow aging progression due to the antioxidant potential attributed to
      retinoids. Nonetheless, vitamin A elicits a myriad of side effects that result
      from either therapeutic or inadvertent intake at varying doses for different
      periods. The mechanism behind such effects remains to be elucidated. In this
      regard, we performed the present work aiming to investigate the effects of
      vitamin A supplementation at 100, 200, or 500IU/kgday(-1) for 2 months on female
      rat brain, analyzing tissue lipid peroxidation levels, antioxidant enzyme
      activities (both Cu/Zn-superoxide dismutase - SOD - and Mn-SOD); glutathione S
      transferase (GST) and monoamine oxidase (MAO) enzyme activity; mitochondrial
      respiratory chain activity and redox parameters in mitochondrial membranes, as
      well as quantifying alpha- and beta-synucleins, beta-amyloid peptide(1-40),
      immunoglobulin heavy-chain binding protein/78kDa glucose-regulated protein
      (BiP/GRP78), receptor for advanced glycation end products (RAGE), D2 receptor,
      and tumor necrosis factor-alpha (TNF-alpha) contents in rat frontal cortex,
      hippocampus, striatum, and cerebellum. We observed increased lipid peroxidation
      marker levels, altered Cu/Zn-SOD and Mn-SOD enzyme activities, mitochondrial
      nitrosative stress, and impaired respiratory chain activity in such brain
      regions. On the other hand, we did not find any change in MAO and GST enzyme
      activities, and on alpha- and beta-synucleins, beta-amyloid peptide(1-40),
      GRP78/BiP, RAGE, D2 receptor, and TNF-alpha contents. Importantly, we did not
      observed any evidence regarding an antioxidant effect of such vitamin at low
      doses in this experimental model. The use of vitamin A as an antioxidant therapy
      among women needs to be reexamined.

PMID- 21856384
TI  - Cytotoxic nor-dammarane triterpenoids from Dysoxylum hainanense.
AB  - Four new nor-dammarane triterpenoids, 12beta-O-acetyl-15alpha,28-dihydoxy-17beta
      methoxy-3-oxo-20,21,22-23,24,25,26,27-octanordammanran (1), 12beta-O-acetyl
      15alpha,17beta,28-trihydoxy-3-oxo-20,21,22-23,24,25,26,27-octanordammanran (2),
      12beta-O-acetyl-15alpha,28-dihydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27
      octanordammanran (3), and 12beta,15alpha,17beta,28-tetrahydoxy-3-oxo-20,21,22
      23,24,25,26,27-octanordammanran (4), were isolated from the 70% EtOH extract of
      Dysoxylum hainanense. The structures of the new compounds were elucidated by
      spectral methods. All the triterpenoids were in vitro evaluated for their
      cytotoxic activities against four tumor cell lines (A549, SK-OV-3, SKMEL-2 and
      HCT15).

PMID- 21856385
TI  - Neuroprotective cadinane sesquiterpenes from the resinous exudates of Commiphora
      myrrha.
AB  - Three new cadinane sesquiterpenes, commiterpenes A-C, were isolated from the
      resinous exudates of Commiphora myrrha. Their structures and relative
      configurations were elucidated by spectroscopic methods (IR, ESIMS, HRESIMS, 1D
      and 2D NMR). All the isolated sesquiterpenes showed neuroprotective effects
      against MPP+-induced neuronal cell death in SH-SY5Y cells.

PMID- 21856378
TI  - The long history of iron in the Universe and in health and disease.
AB  - BACKGROUND: Not long after the Big Bang, iron began to play a central role in the
      Universe and soon became mired in the tangle of biochemistry that is the prima
      essentia of life. Since life's addiction to iron transcends the oxygenation of
      the Earth's atmosphere, living things must be protected from the potentially
      dangerous mix of iron and oxygen. The human being possesses grams of this
      potentially toxic transition metal, which is shuttling through his oxygen-rich
      humor. Since long before the birth of modern medicine, the blood-vibrant red from
      a massive abundance of hemoglobin iron-has been a focus for health experts. SCOPE
      OF REVIEW: We describe the current understanding of iron metabolism, highlight
      the many important discoveries that accreted this knowledge, and describe the
      perils of dysfunctional iron handling. GENERAL SIGNIFICANCE: Isaac Newton
      famously penned, "If I have seen further than others, it is by standing upon the
      shoulders of giants". We hope that this review will inspire future scientists to
      develop intellectual pursuits by understanding the research and ideas from many
      remarkable thinkers of the past. MAJOR CONCLUSIONS: The history of iron research
      is a long, rich story with early beginnings, and is far from being finished. This
      article is part of a Special Issue entitled Transferrins: Molecular mechanisms of
      iron transport and disorders.

PMID- 21856386
TI  - A new steroidal saponin with antiinflammatory and antiulcerogenic properties from
      the bulbs of Allium ampeloprasum var. porrum.
AB  - A new steroidal saponin was isolated from the bulbs of Allium ampeloprasum var.
      porrumL. On the basis of chemical evidence, comprehensive spectroscopic analyses
      and comparison of known compounds, its structure was established as
      (3beta,5alpha,6beta,25R)-6-[(beta-D-glucopyranosyl)oxy]-spirostan-3-yl O-beta-D
      glucopyranosyl-(1->2)-O-[beta-D-glucopyranosyl-(1->3)]-beta-D-galactopyranoside.
      Results of the present study indicated that the steroidal saponin showed
      haemolytic effects in the in vitro assays and demonstrated antiinflammatory
      activity and gastroprotective property using in vivo models.

PMID- 21856387
TI  - Down regulation of gene related sex hormone synthesis pathway in mouse testes by
      miroestrol and deoxymiroestrol.
AB  - Miroestrol and deoxymiroestrol are phytoestrogens isolated from tuberous root of
      Pueraria candollei var. mirifica. Modulatory effects of miroestrol and
      deoxymiroestrol on enzymes involved in sex-hormone synthesis pathway in male
      C57BL/6 mice were investigated using semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). Miroestrol and deoxymiroestrol suppressed the
      expressions of 3beta-HSD, 17beta-HSD1, and CYP17 while CYP19 mRNA expression was
      slightly decreased. In addition, the expression of 17beta-HSD2 was induced in
      correlation with those did by estradiol. These observations supported that
      miroestrol and deoxymiroestrol could exhibit the same effect as estradiol
      regarding regulation of testicular gene related sex hormone synthesis pathway.

PMID- 21856388
TI  - Two new pterosin dimers from Pteris mutifida Poir.
AB  - Two new C14 pterosin dimers, which are a pair of isomers named as bimutipterosins
      A (1) and B (2), were isolated from the whole plant of Pteris multifida. Their
      structures have been elucidated on the basis of NMR and MS data. From a
      biogenetic point of view, these compounds including a cyclobutane basic core
      should be considered as a [2+2] dimerization product of dehydropterosin Q, which
      was a known compound and also isolated from this plant. This novel type of
      pterosin dimer was reported here for the first time. Compounds 1 and 2 showed
      cytotoxicity against HL 60 cell line (human leukemia) with the IC50 values of
      12.8 and 26.6 MUM, respectively.

PMID- 21856389
TI  - Tracking of food quantity by coyotes (Canis latrans).
AB  - Previous studies have demonstrated that Weber's Law mediates quantitative
      discrimination abilities across various species. Here, we tested coyotes' (Canis
      latrans) ability to discriminate between various quantities of food and
      investigated whether this ability conforms to predictions of Weber's Law. We
      demonstrate herein that coyotes are capable of reliably discriminating large
      versus small quantities of discrete food items. As predicted by Weber's Law,
      coyotes' quantitative discrimination abilities are mediated by the ratio between
      the large and small quantities of food and exhibit scalar variability.
      Furthermore, in this task coyotes were not discriminating large versus small
      quantities based on olfactory cues alone.

PMID- 21856390
TI  - In utero and lactational exposure to Aroclor 1254 affects bone geometry, mineral
      density and biomechanical properties of rat offspring.
AB  - Exposure to polychlorinated biphenyls (PCBs) induce a broad spectrum of toxic
      effects in various organs including bone. The most susceptible age-groups to the
      toxic effects of PCBs are foetuses and infants. The aim of the present study was
      to quantitatively evaluate changes in bone geometry, mineral density and
      biomechanical properties following perinatal exposure to the PCB mixture, Aroclor
      1254 (A1254), and to examine the persistence of observed bone alterations by
      following the offspring over time. Sprague-Dawley rat offspring were exposed to
      A1254 from gestational day 1 to post-natal day (PND) 23. Femur and tibia were
      collected on PNDs 35, 77 and 350 and were analyzed by peripheral quantitative
      computed tomography and biomechanical testing. At PND35, exposure to A1254
      induced short, thin femur and tibia, with reduced mechanical strength of femoral
      neck. No treatment-related bone changes were detected in offspring at PND77 or
      PND350. In conclusion, the present investigation suggests that perinatal exposure
      to A1254 leads to shorter, thinner and weaker bones in juvenile rats at PND35,
      with these effects being absent at later time-points as exposure is discontinued.
      The results indicate that the observed bone effects are mainly driven by the
      dioxin-like congeners, although it cannot exclude the contribution of the non
      dioxin-like congeners to the exposure outcome.

PMID- 21856391
TI  - Activation of Trim17 by PPARgamma is involved in di(2-ethylhexyl) phthalate
      (DEHP)-induced apoptosis on Neuro-2a cells.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastics.
      Its reproductive toxicity and teratogenic effects are well known. DEHP can cause
      liver damage and peroxisome proliferation, as well as carcinogenesis. Animal
      study has shown that DEHP causes neurodegeneration in rat brain. Prenatal
      exposure to DEHP disrupts brain development and decreases brain weight in rats.
      But its mechanism of action in the brain is not clear. This study used a
      neuroblastoma cell line, Neuro-2a cells, to investigate the toxic effect of DEHP.
      The results revealed that DEHP inhibits cell proliferation, activate caspase-3,
      induce apoptosis in a dose and time dependent manner, and activate expression of
      the PPARgamma and Trim17 protein. Administration of the PPARgamma agonist
      (troglitazone) enhanced DEHP-induced Trim17 protein expression and this
      enhancement could be reversed by the PPARgamma antagonist (GW9662). These results
      suggest that DEHP activates the Trim17 protein via PPARgamma leading to cleavage
      pro-caspase-3 and apoptosis. This finding may account for the central nervous
      system toxicity of DEHP and implies DEHP can impair fetal brain development.

PMID- 21856392
TI  - Synthesis and evaluation of poly(styrene-co-maleic acid) micellar nanocarriers
      for the delivery of tanespimycin.
AB  - Polymeric micelles carrying the heat shock protein 90 inhibitor tanespimycin (17
      N-allylamino-17-demethoxygeldanamycin) were synthesized using poly(styrene-co
      maleic acid) (SMA) copolymers and evaluated in vitro and in vivo. SMA
      tanespimycin micelles were prepared with a loading efficiency of 93%. The
      micelles incorporated 25.6% tanespimycin by weight, exhibited a mean diameter of
      74 +/- 7 nm by dynamic light scattering and a zeta potential of -35 +/- 3 mV.
      Tanespimycin was released from the micelles in a controlled manner in vitro, with
      62% released in 24h from a pH 7.4 buffer containing bovine serum albumin. The
      micellar drug delivery systems for tanespimycin showed potent activity against
      DU145 human prostate cancer cells, with an IC(50) of 230 nM. They further
      exhibited potent anti-cancer activity in vivo in nu/nu mice bearing subcutaneous
      DU145 human prostate cancer tumor xenografts, with significantly higher
      anticancer efficacy as measured by tumor regression when compared to free
      tanespimycin at an equivalent single dose of 10mg/kg. These data suggest further
      investigation of SMA-tanespimycin as a promising agent in the treatment of
      prostate cancer.

PMID- 21856393
TI  - Mucoadhesive platforms for targeted delivery to the colon.
AB  - A novel platform system, comprising a mucoadhesive core and a rapid release
      carrier, was designed for targeted drug delivery to the colon. Prednisolone
      pellets containing different carbomers, including Carbopol 971P, Carbopol 974P
      and Polycarbophil AA-1, with or without organic acids, were produced by extrusion
      spheronization. Mucoadhesive pellets were coated with a new enteric double
      coating system, which dissolves at pH 7. This system comprises an inner layer of
      partially neutralized Eudragit S and buffer salt and an outer coating of standard
      Eudragit S. A single layer of standard Eudragit S was also applied for comparison
      purposes. Dissolution of the coated pellets was assessed in USP II apparatus in
      0.1N HCl followed by Krebs bicarbonate buffer pH 7.4. Visualization of the
      coating dissolution process was performed by confocal laser scanning microscopy
      using fluorescent markers in both layers. The mucoadhesive properties of
      uncoated, single-coated and-double coated pellets were evaluated ex vivo on
      porcine colonic mucosa. Mucoadhesive pellets coated with a single layer of
      Eudragit S release its cargo after a lag time of 120 min in Krebs buffer. In
      contrast, drug release from the double-coated mucoadhesive pellets was
      significantly accelerated, starting at 75 min. In addition, the mucoadhesive
      properties of the core of the double coated pellets were higher than those from
      single-coated pellets after the core had been exposed to the buffer medium. This
      novel platform technology has the potential to target the colon and overcome the
      variability in transit and harmonize drug release and bioavailability.

PMID- 21856394
TI  - Calcium condensed cell penetrating peptide complexes offer highly efficient, low
      toxicity gene silencing.
AB  - The development of short-interfering RNA (siRNA) offers new strategies for
      manipulating specific genes responsible for pathological disorders. Myriad
      cationic polymer and lipid formulations have been explored, but an effective, non
      toxic carrier remains a major barrier to clinical translation. Among the emerging
      candidates for siRNA carriers are cell penetrating peptides (CPPs), which can
      traverse the plasma membrane and facilitate the intracellular delivery of siRNA.
      Previously, a highly efficient and non-cytotoxic means of gene delivery was
      designed by complexing plasmid DNA with CPPs, then condensing with calcium. Here,
      the CPP TAT and a longer, 'double' TAT (dTAT) were investigated as potential
      carriers for siRNA. Various N/P ratios and calcium concentrations were used to
      optimize siRNA complexes in vitro. Upon addition of calcium, 'loose' siRNA/CPP
      complexes were condensed into small nanoparticles. Knockdown of luciferase
      expression in the human epithelial lung cell line A549-luc-C8 was high (up to
      93%) with no evidence of cytotoxicity. Selected formulations of the dTAT
      complexes were dosed intravenously up to 1000 mg/kg with minimal toxicity.
      Biodistribution studies revealed high levels of gene knockdown in the lung and
      muscle tissue suggesting these simple vectors may offer a translatable approach
      to siRNA delivery.

PMID- 21856395
TI  - In vitro and in vivo iontophoretic transdermal delivery of an anti-parkinsonian
      agent.
AB  - To objective of this work was to study the feasibility of iontophoretic delivery
      of SLV 318 (7-(4-benzyl-1-piperazinyl)-2(3H)-benzoxazolone methanesulfonate)
      across hairless rat skin in vitro and in vivo. The effect of counter-ions and
      temperature were investigated for optimizing SLV 318 solubility. The effect of
      electrode efficiency and total current applied on the delivery of SLV 318 were
      studied using Franz diffusion cells and samples were analyzed using HPLC.
      Delivery increased with increasing concentration. For current-time combinations,
      electrode had to be replaced every 9h. Passive, iontophoretic (0.1 mA/cm(2) for
      1h) and intravenous studies were performed in vivo. Blood samples collected were
      analyzed using LC-MS/MS. SLV 318 had higher solubility with NaCl (75 mM) as a
      counter-ion at 25 degrees C than with other counter-ions tested. In vivo
      iontophoresis significantly enhanced the permeation and also reduced its lag time
      (P<0.05). The C(max) of SLV 318 during 1h iontophoresis was 6.56 +/- 0.68 ng/mL
      at 1.31 +/- 0.29 h (T(max)) as compared to 2.96 +/- 0.29 ng/mL at 25.32 +/- 0.67
      h (T(max)) by 24h passive permeation. The in vitro and in vivo data has shown the
      feasibility to enhance delivery of SLV 318 by iontophoresis.

PMID- 21856396
TI  - Plasma pharmacochemistry based approach to screening potential bioactive
      components in Huang-Lian-Jie-Du-Tang using high performance liquid chromatography
      coupled with mass spectrometric detection.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Tang (HLJDT), a classic
      prescription of traditional Chinese medicine (TCM), has been used in clinical
      over 1700 years for the treatment of gastrointestinal disorders, cardiovascular
      diseases and Alzheimer disease. But the active components of HLJDT were
      ambiguous, which seriously restricted its clinical application. MATERIALS AND
      METHODS: The methodology of plasma pharmacochemistry was applied to screen the
      bioactive components in HLJDT. A reliable LC/MS system was established for
      detecting the prototype compounds and metabolites in dosed plasma after oral
      administration of HLJDT. By comparative analysis of the chemical profiles of
      HLJDT extracts, blank plasma and dosed plasma, potential bioactive compounds in
      HLJDT may be discovered. RESULTS: By comparing the retention time, MS and MS/MS
      spectra with those of reference standard and literature data, 30 components
      including 22 prototype compounds and 8 metabolites from HLJDT were discovered as
      potential bioactive components in rat plasma. CONCLUSIONS: A reliable and
      effective method was established to screen the potential bioactive components in
      the formula of HLJDT, which provided useful information for the further study of
      action mechanism of HLJDT.

PMID- 21856397
TI  - Protective effects of muscone on ischemia-reperfusion injury in cardiac myocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Musk has been traditionally used in Chinese
      medicine as the main ingredient of many formulations for the treatment of chest
      pain and angina pectoris. AIM OF THE STUDY: To investigate the protective effects
      of muscone (the active ingredient of musk) on ischemia-reperfusion (I/R) injury
      induced by hypoxia and low glucose in primary cultured rat cardiac myocytes.
      MATERIALS AND METHODS: Primary cultures of neonatal rat cardiac myocytes were
      subjected to ischemia-reperfusion in media, with or without muscone. Cell
      viability, release of lactic acid dehydrogenase (LDH), superoxide dismutase (SOD)
      activity, malondialdehyde (MDA) levels, creatine kinase (CK) and caspase-3
      activities, as well as intracellular free Ca(2+) concentrations, were measured.
      Cellular apoptosis and mitochondrial membrane potential (MMP) were assessed by
      flow cytometry, and the expression of Bcl-2 and Bax proteins was assessed by
      Western blotting. RESULTS: Following the exposure of cardiac myocytes to ischemia
      reperfusion, there was a marked decrease in pulsating frequency, cell viability,
      SOD activity, MMP, and the expression of Bcl-2 protein, accompanied by increased
      LDH release, MDA production, CK and caspase-3 activities, intracellular free
      Ca(2+) concentrations, rate of apoptosis, and expression of Bax protein.
      Pretreatment with muscone (0.215, 0.43, 0.86 MUg/mL) prior to I/R injury
      significantly attenuated the above changes. CONCLUSION: Muscone has a protective
      effect against I/R injury in cardiac myocytes, indicating that muscone may
      potentially provide therapeutic benefit in I/R injury by inhibiting cellular
      oxidative stress and apoptosis.

PMID- 21856398
TI  - Anti-inflammatory effects of Polygala tenuifolia root through inhibition of NF
      kappaB activation in lipopolysaccharide-induced BV2 microglial cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Polygala tenuifolia Willd is a well
      known traditional Oriental medicine and has been prescribed for treatment of
      dysfunction in memorial systems and various brain inflammatory diseases. The
      present study was designed to validate the anti-inflammatory effects of the water
      extract of Polygala tenuifolia root (WEPT). MATERIALS AND METHODS: The anti
      inflammatory properties of WEPT were studied using lipopolysaccharide (LPS)
      stimulated murine BV2 microglia model. As inflammatory parameters, the production
      of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2,
      prostaglandin E(2) (PGE(2)), tumor necrosis factor (TNF)-alpha, and interleukin
      (IL)-1beta were evaluated. We also examined the extract's effect on the activity
      of nuclear factor-kappaB (NF-kappaB), and toll-like receptor 4 (TLR4) and myeloid
      differentiation factor 88 (Myd-88) expression. RESULTS: WEPT suppressed LPS
      induced production of NO, PGE(2), and expression of iNOS and COX-2 in a dose
      dependent manner, without causing cytotoxicity. It also significantly reduced
      generation of proinflammatory cytokines, including IL-1beta and TNF-alpha. In
      addition, WEPT suppressed NF-kappaB translocation by blockade of IkappaB-alpha
      (IkappaB-alpha) degradation and inhibited TLR4 and Myd-88 expression in LPS
      stimulated BV2 cells. CONCLUSIONS: These results indicate that the inhibitory
      effects of WEPT on LPS-stimulated inflammatory mediator production in BV2
      microglia are associated with suppression of the NF-kappaB and toll-like receptor
      signaling pathways. Therefore, Polygala tenuifolia extracts may be useful in
      treatment of neurodegenerative diseases by inhibition of inflammatory mediator
      production in activated microglia.

PMID- 21856399
TI  - The protective effect of Salvia miltiorrhiza in an animal model of early
      experimentally induced diabetic nephropathy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is the most common
      cause of end stage renal disease. In this study, the effects of Salvia
      miltiorrhiza (SM) were studied in an experimental rat model of DN that was
      induced by streptozotocin (STZ) treatment. MATERIALS AND METHODS: Diabetes was
      induced in male Sprague-Dawley rats (290 +/- 10 g) by injecting STZ (45 mg/kg)
      into the tail vein. After development of diabetes, the rats were treated with SM
      (500 mg/kg) for 8 weeks in order to analyze its renoprotective effect, which was
      evaluated by means of blood glucose level, urine protein, and the expression of
      advanced glycation end-products (AGEs), receptor of advanced glycation end
      products (RAGE), transforming growth factor beta1 (TGF-beta1), collagen IV, and
      monocyte/macrophage (ED-1) infiltration. RESULTS: High levels of 24-h urinary
      protein excretion were ameliorated by SM. Moreover, the serum and kidney levels
      of transforming growth factor beta1 (TGF-beta1) and the kidney levels of collagen
      IV, monocytes/macrophages (ED-1) and the receptor for advanced glycation end
      products (RAGE), were significantly reduced. CONCLUSIONS: These findings suggest
      that SM might inhibit the progression of DN and could be a therapeutic agent for
      regulating several pharmacological targets for treatment or prevention of DN.

PMID- 21856400
TI  - Where bio meets nano: the many uses for nanoporous aluminum oxide in
      biotechnology.
AB  - Porous aluminum oxide (PAO) is a ceramic formed by an anodization process of pure
      aluminum that enables the controllable assembly of exceptionally dense and
      regular nanopores in a planar membrane. As a consequence, PAO has a high
      porosity, nanopores with high aspect ratio, biocompatibility and the potential
      for high sensitivity imaging and diverse surface modifications. These properties
      have made this unusual material attractive to a disparate set of applications.
      This review examines how the structure and properties of PAO connect with its
      present and potential uses within research and biotechnology. The role of PAO is
      covered in areas including microbiology, mammalian cell culture, sensitive
      detection methods, microarrays and other molecular assays, and in creating new
      nanostructures with further uses within biology.

PMID- 21856401
TI  - Systems biology of the metabolic network regulated by the Akt pathway.
AB  - Cancer has been proposed as an example of systems biology disease or network
      disease. Accordingly, tumor cells differ from their normal counterparts more in
      terms of intracellular network dynamics than single markers. Here we shall focus
      on a recently recognized hallmark of cancer, the deregulation of cellular
      energetics. The constitutive activation of the phosphatidylinositol 3-kinase
      (PI3K)/Akt pathway has been confirmed as an essential step toward cell
      transformation. We will consider how the effects of Akt activation are connected
      with cell metabolism; more precisely, we will review existing metabolic models
      and discuss the current knowledge available to construct a kinetic model of the
      most relevant metabolic processes regulated by the PI3K/Akt pathway. The model
      will enable a systems biology approach to predict the metabolic targets that may
      inhibit cell growth under hyper activation of Akt.

PMID- 21856402
TI  - Lactulose: production, purification and potential applications.
AB  - Lactulose a "bifidus factor" is composed of galactose and fructose, which can be
      produced by the isomerization of lactose. It is a prebiotic carbohydrate which
      stimulates the growth of health-promoting bacteria in the gastrointestinal tract,
      such as bifidobacteria and lactobacilli and at the same time inhibits growth of
      pathogenic bacteria such as Salmonella. It can also be used for the treatment of
      constipation, hepatic encephalopathy, tumour prevention, and to maintain blood
      glucose and insulin level. This review provides comprehensive information on the
      different techniques used for the production of lactulose, purification and
      analysis. Besides this mechanism of action and its potential applications in food
      and pharmaceutical industries have also been discussed.

PMID- 21856403
TI  - GMP issues for recombinant plant-derived pharmaceutical proteins.
AB  - Recombinant proteins can be produced in a diverse array of plant-based systems,
      ranging from whole plants growing in the soil to plant suspension cells growing
      in a fully-defined synthetic medium in a bioreactor. When the recombinant
      proteins are intended for medical use (plant-derived pharmaceutical proteins,
      PDPs) they fall under the same regulatory guidelines for manufacturing that cover
      drugs from all other sources, and when such proteins enter clinical development
      this includes the requirement for production according to good manufacturing
      practice (GMP). In principle, the well-characterized GMP regulations that apply
      to pharmaceutical proteins produced in bacteria and mammalian cells are directly
      transferrable to plants. In practice, the cell-specific terminology and the
      requirement for a contained, sterile environment mean that only plant cells in a
      bioreactor fully meet the original GMP criteria. Significant changes are required
      to adapt these regulations for proteins produced in whole-plant systems and it is
      only recently that the first GMP-compliant production processes using plants have
      been delivered.

PMID- 21856404
TI  - Designing the perfect plant feedstock for biofuel production: using the whole
      buffalo to diversify fuels and products.
AB  - Petroleum-derived liquid fuels and commodities play a part in nearly every aspect
      of modern daily life. However, dependence on this one natural resource to
      maintain modern amenities has caused negative environmental and geopolitical
      ramifications. In an effort to replace petroleum, technologies to synthesize
      liquid fuels and other commodities from renewable biomass are being developed.
      Current technologies, however, only use a portion of plant biomass feedstocks for
      fuel and useful products. "Using the whole feedstock buffalo" or optimally using
      all portions and biochemicals present in renewable biomass will enhance the
      economic and environmental feasibility of biofuels and coproducts. To accomplish
      this optimization, greater understanding of the relationship between liquid fuel
      and bioproduct properties and plant chemistries is needed. Liquid fuel properties
      and how they relate to biochemistry and petrochemistry are discussed. Enhanced
      biofuel yields and high-value commodities from biomass are needed to sustainably
      replace petroleum-based products. Several metabolic engineering strategies are
      discussed. We will describe paths of possible fuel and product diversification
      using dedicated lignocellulosic biomass (e.g., switchgrass).

PMID- 21856405
TI  - CO2 utilizing microbes--a comprehensive review.
AB  - CO2 fixing microbes are the species primarily engaged in complexing the inorganic
      carbon dioxide to organic carbon compounds. There are many microorganisms from
      archaeal and bacterial domain that can fix carbon dioxide through six known CO2
      fixing pathways. These organisms are ubiquitous and can survive in wide range of
      aerobic and anaerobic habitats. This review focuses on the prior research, that
      has been conducted in this field and presents a summarized overview of all the
      mechanisms (along with their genes and enzymes) used by these microbes for CO2
      incorporation. In addition, this review provides a better understanding of
      diversity and taxonomy of CO2 fixing microorganisms. The information presented
      here will motivate researchers to further explore the diversity of CO2 fixing
      microorganisms as well as to decipher the underlying mechanisms of CO2
      utilization.

PMID- 21856406
TI  - Advances and applications of binding affinity prediction methods in drug
      discovery.
AB  - Nowadays, the improvement of R&D productivity is the primary commitment in
      pharmaceutical research, both in big pharma and smaller biotech companies. To
      reduce costs, to speed up the discovery process and to increase the chance of
      success, advanced methods of rational drug design are very helpful, as
      demonstrated by several successful applications. Among these, computational
      methods able to predict the binding affinity of small molecules to specific
      biological targets are of special interest because they can accelerate the
      discovery of new hit compounds. Here we provide an overview of the most widely
      used methods in the field of binding affinity prediction, as well as of our own
      work in developing BEAR, an innovative methodology specifically devised to
      overtake some limitations in existing approaches. The BEAR method was
      successfully validated against different biological targets, and proved its
      efficacy in retrieving active compounds from virtual screening campaigns. The
      results obtained so far indicate that BEAR may become a leading tool in the drug
      discovery pipeline. We primarily discuss advantages and drawbacks of each
      technique and show relevant examples and applications in drug discovery.

PMID- 21856407
TI  - Developmental differences in peripheral glabrous skin mechanosensory nerve
      receptive field and intracellular electrophysiologic properties: phenotypic
      characterization in infant and juvenile rats.
AB  - Developmental differences in peripheral neuron characteristics and functionality
      exist. Direct measurement of active and passive electrophysiologic and receptive
      field characteristics of single mechanosensitive neurons in glabrous skin was
      performed and phenotypic characterization of fiber subtypes was applied to
      analyze developmental differences in peripheral mechanosensitive afferents. After
      Institutional approval, male Sprague-Dawley infant (P7: postnatal day 7) and
      juvenile (P28) rats were anesthetized and single cell intracellular
      electrophysiology was performed in the dorsal root ganglion (DRG) soma of
      mechanosensitive cells with receptive field (RF) in the glabrous skin of the
      hindpaw. Passive and active electrical properties of the cells and RF size and
      characteristics determined. Fiber subtype classification was performed and
      developmental differences in fiber subtype properties analyzed. RF size was
      smaller at P7 for both low and high threshold mechanoreceptor (LTMR and HTMR)
      with no differences between A- and C-HTMR (AHTMR and CHTMR). The RF size was also
      correlated to anatomic location on glabrous skin, toes having smaller RF.
      Conduction velocity (CV) was adequate at P28 for AHTMR and CHTMR classification,
      but not at P7. Only width of the action potential at half height (D50) was
      significantly different between HTMR at P7, while D50, CV and amplitude of the AP
      were significant for HTMR at P28. RF size is determined in part by the RF
      distribution of the peripheral neuron. Developmental differences in RF size occur
      with larger RF sizes occurring in younger animals. This is consistent with RF
      size differences determined by measuring RF in the spinal cord, except the
      peripheral RF is much smaller, more refined, and in some cases pinpoint.
      Developmental differences make CV alone unreliable for neuron classification.
      Utilizing integration of all measured parameters allows classification of neurons
      into subtypes even at the younger ages. This will prove important in
      understanding changes that occur in the peripheral sensory afferents in the face
      of ongoing development and injury early in life.

PMID- 21856408
TI  - Activity-dependent reduction of dopamine D2 receptors during a postnatal critical
      period of plasticity in rat striatum is not affected by prenatal haloperidol
      treatment.
AB  - Motor activity induced in the Circling Training test (CT) during a postnatal (PN)
      critical period of plasticity (PN30-37) produces a long-lasting decrease in the
      number of binding sites and mRNA expression levels of the dopamine D2 receptor
      (D2R) in rat striatum. Prenatal exposure to the antipsychotic haloperidol also
      decreases postnatal levels of the striatal D2R in the offspring. We examined
      whether such fetal exposure to haloperidol could affect the activity-dependent
      reduction of the D2R system during the critical period. Half of the male
      offspring exposed to either haloperidol (2.5 mg/kg/day), i.p.) or saline during
      gestational days 5-18 were subjected to the CT during the critical period, while
      the remaining represented CT control animals. The adult number of binding sites
      and mRNA expression levels of the striatal D2R at PN90 were not changed by
      prenatal haloperidol treatment alone. On the other hand, only pups subjected to
      the CT during the critical period showed decreases in both studied parameters,
      regardless the prenatal treatment. These findings indicated that the postnatal
      reduction of the striatal D2R binding induced prenatally by haloperidol does not
      affect long-lasting activity-dependent plastic changes on the same receptor
      system elicited by motor activity in an ontogenetic critical period of plasticity
      in rat striatum.

PMID- 21856409
TI  - Octyl and dodecyl gallates induce oxidative stress and apoptosis in a melanoma
      cell line.
AB  - This study investigated the mechanism of cytotoxicity of octyl (G8) and dodecyl
      (G12) gallates in a murine melanoma cell line (B16F10). For this purpose, several
      methods to measure cell viability were used to determine if the cytotoxicity
      induced by these gallates corresponds to a general or an organelle-specific
      effect. Furthermore, the mechanisms related to apoptosis were examined, by
      studying the caspase-3 activity, oxidative stress, mitochondrial potential and
      the expression of anti- or proapoptotic proteins. When comparing the various
      methods of assessing cell viability, the tested gallates showed a higher
      cytotoxicity in the assay that indicates lysosomal activity, compared with the
      assays that indicate mitochondrial and ribosomal activities. Both gallates
      promoted the release of lactate dehydrogenase into the medium, indicating an
      effect on cell membrane integrity. The gallates also promoted cellular oxidative
      stress, mitochondrial depolarization and an increase in caspase-3 activity.
      Furthermore, the gallates induced an increase in proapoptotic (Bax) and a
      decrease in antiapoptotic (Bcl-2) proteins expression. Our results indicate that
      the apoptotic cell death induced by G8 and G12 in B16F10 cells involves lipid
      membrane damages, lysosomal and mitochondrial dysfunction, which was accompanied
      by alterations in apoptotic proteins expression and seems to be triggered by
      cellular oxidative stress.

PMID- 21856410
TI  - In silico prediction of rhabdomyolysis of compounds by self-organizing map and
      support vector machine.
AB  - Rhabdomyolysis is a potentially lethal syndrome resulting in leakage of myocyte
      intracellular contents into the plasma. Some drugs, such as lipid-lowering drugs
      and antihistamines, can cause rhabdomyolysis. In this work, a dataset containing
      186 chemical compounds causing rhabdomyolysis and 117 drugs not causing
      rhabdomyolysis was collected. The dataset was split into a training set
      (containing 230 compounds) and a test set (containing 73 compounds). A Kohonen's
      self-organizing map (SOM) and a support vector machine (SVM) were applied to
      develop classification models to differentiate compounds causing and not causing
      rhabdomyolysis. Using the SOM method, classification accuracies of 93.3% for the
      training set and 84.5% for the test set were achieved; using the SVM method,
      classification accuracies of 95.2% for the training set and 84.9% for the test
      set were achieved. In addition, the extended connectivity fingerprints (ECFP_4)
      for all the molecules were calculated and analyzed to find the important features
      of molecules relating to rhabdomyolysis.

PMID- 21856411
TI  - Comparative pharmacokinetics of perfluorohexanesulfonate (PFHxS) in rats, mice,
      and monkeys.
AB  - Perfluorohexanesulfonate (PFHxS) has been found in biological samples from
      wildlife and humans. The human geometric mean serum PFHxS elimination half-life
      has been estimated to be 2665days. A series of studies was undertaken to
      establish pharmacokinetic parameters for PFHxS in rats, mice, and monkeys after
      single administration with pharmacokinetic parameters determined by
      WinNonlin((r)) software. Rats and mice appeared to be more effective at
      eliminating PFHxS than monkeys. With the exception of female rats, which had
      serum PFHxS elimination half-life of approximately 2 days, the serum elimination
      half-lives in the rodent species and monkeys approximated 1month and 4months,
      respectively, when followed over extended time periods (10-24weeks).
      Collectively, these studies provide valuable insight for human health risk
      assessment regarding the potential for accumulation of PFHxS in humans.

PMID- 21856412
TI  - Inhibition of aldose reductase prevents endotoxin-induced inflammation by
      regulating the arachidonic acid pathway in murine macrophages.
AB  - The bacterial endotoxin lipopolysaccharide (LPS) is known to induce release of
      arachidonic acid (AA) and its metabolic products, which play important roles in
      the inflammatory process. We have shown earlier that LPS-induced signals in
      macrophages are mediated by aldose reductase (AR). Here we have investigated the
      role of AR in LPS-induced release of AA metabolites and their modulation using a
      potent pharmacological inhibitor, fidarestat, and AR siRNA ablation in RAW264.7
      macrophages and AR-knockout mouse peritoneal macrophages and heart tissue.
      Inhibition or genetic ablation of AR prevented the LPS-induced synthesis and
      release of AA metabolites such as PGE2, TXB, PGI2, and LTBs in macrophages. LPS
      induced activation of cPLA2 was also prevented by AR inhibition. Similarly, AR
      inhibition also prevented the calcium ionophore A23187-induced cPLA2 and LTB4 in
      macrophages. Further, AR inhibition by fidarestat prevented the expression of AA
      metabolizing enzymes such as COX-2 and LOX-5 in RAW264.7 cells and AR-knockout
      mouse-derived peritoneal macrophages. LPS-induced expression of AA-metabolizing
      enzymes and their catalyzed metabolic products was significantly lower in
      peritoneal macrophages and heart tissue from AR-knockout mice. LPS-induced
      activation of redox-sensitive signaling intermediates such as MAPKs,
      transcription factor NF-kappaB, and EGR-1, a transcriptional regulator of mPGES
      1, which in collaboration with COX-2 leads to the production of PGE2, was also
      significantly prevented by AR inhibition. Taken together, our results indicate
      that AR mediates LPS-induced inflammation by regulating the AA-metabolic pathway
      and thus provide a novel role for AR inhibition in preventing inflammatory
      complications such as sepsis.

PMID- 21856413
TI  - Effects of neonatal methamphetamine treatment on adult stress-induced
      corticosterone release in rats.
AB  - In rats, neonatal (+)-methamphetamine (MA) exposure and maternal separation
      stress increase corticosterone during treatment and result in learning and memory
      impairments later in life. Early-life stress also changes later responses to
      acute stress. We tested the hypothesis that neonatal MA exposure would alter
      adult corticosterone after acute stress or MA challenge. Rats were treated with
      MA (10 mg/kg * 4/day), saline, or handling on postnatal (P) days 11-15 or 11-20
      (days that lead to learning and memory impairments at this dose). As adults,
      corticosterone was measured before and after 15 min forced swim (FS) or 15 min
      forced confinement (FC), counterbalanced, and after an acute MA challenge (10
      mg/kg) given last. FS increased corticosterone more than FC; order and stress
      type interacted but did not interact with treatment; treatment interacted with FS
      but not with FC. In the P11-15 regimen, MA-treated rats showed more rapid
      increases in corticosterone after FS than controls. In the P11-20 regimen, MA
      treated rats showed a trend toward more rapid decrease in corticosterone after
      FS. No differences were found after MA challenge. The data do not support the
      hypothesis that neonatal MA causes changes in adult stress responsiveness to FS,
      FC, or an acute MA challenge.

PMID- 21856414
TI  - Cortical cultures coupled to micro-electrode arrays: a novel approach to perform
      in vitro excitotoxicity testing.
AB  - In vitro neuronal cultures exhibit spontaneous electrophysiological activity that
      can be modulated by chemical stimulation and can be monitored over time by using
      Micro-Electrode Arrays (MEAs), devices composed by a glass substrate and metal
      electrodes. Dissociated networks respond to transmitters, their blockers and many
      other pharmacological substances, including neurotoxic compounds. In this paper
      we present results related to the effects, both acute (i.e. 1 hour after the
      treatment) and chronic (3 days after the treatment), of increasing glutamatergic
      transmission induced by the application of rising concentrations of glutamate and
      its agonists (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid - AMPA, N
      methyl-D-aspartate - NMDA and AMPA together with cyclothiazide - CTZ). Increase
      of available glutamate was obtained in two ways: 1) by direct application of
      exogenous glutamate and 2) by inhibiting the clearance of the endogenously
      released glutamate through DL-threo-beta-benzyloxyaspartate (TBOA). Our findings
      show that fine modulations (i.e. low concentrations of drug) of the excitatory
      synaptic transmission are reflected in the electrophysiological activation of the
      network, while intervention leading to excessive direct stimulation of
      glutamatergic pathways (i.e. medium and high concentrations of drug) results in
      the abolishment of the electrophysiological activity and eventually cell death.
      The results obtained by means of the MEA recordings have been compared to the
      analysis of cell viability to confirm the excitotoxic effect of the applied drug.
      In conclusion, our study demonstrates that MEA-coupled cortical networks are very
      sensitive to pharmacological manipulation of the excitatory ionotropic
      glutamatergic transmission and might provide sensitive endpoints to detect acute
      and chronic neurotoxic effects of chemicals and drugs for predictive toxicity
      testing.

PMID- 21856415
TI  - PP2A targeting by viral proteins: a widespread biological strategy from DNA/RNA
      tumor viruses to HIV-1.
AB  - Protein phosphatase 2A (PP2A) is a large family of holoenzymes that comprises 1%
      of total cellular proteins and accounts for the majority of Ser/Thr phosphatase
      activity in eukaryotic cells. Although initially viewed as constitutive
      housekeeping enzymes, it is now well established that PP2A proteins represent a
      family of highly and sophistically regulated phosphatases. The past decade,
      multiple complementary studies have improved our knowledge about structural and
      functional regulation of PP2A holoenzymes. In this regard, after summarizing
      major cellular regulation, this review will mainly focus on discussing a
      particulate biological strategy, used by various viruses, which is based on the
      targeting of PP2A enzymes by viral proteins in order to specifically deregulate,
      for their own benefit, cellular pathways of their hosts. The impact of such PP2A
      targeting for research in human diseases, and in further therapeutic
      developments, is also discussed.

PMID- 21856416
TI  - Quantitative analysis of rate and extent of tolerance of biomarkers: application
      to nicotinic acid-induced changes in non-esterified fatty acids in rats.
AB  - In this paper we quantitatively evaluate two feedback systems with a focus on
      rate and extent of tolerance and rebound development. In the two feedback
      systems, the regulation of turnover of response is governed by one or several
      moderators. In the basic system, one single moderator inhibits the formation of
      response. This system has been applied to cortisol secretion and serotonin
      reuptake inhibition. The basic system has been extended to adequately describe
      nicotinic acid (NiAc)-induced changes in non-esterified fatty acids (NEFA). In
      the extended system, the feedback is described by a cascade of moderators where
      the first inhibits formation of response and the last stimulates loss of
      response. The objectives of this paper were to analyze these systems from a
      mathematical/analytical and quantitative point of view and to present simulations
      with different parameter settings and dosing regimens in order to highlight the
      intrinsic behaviour of these systems and to present expressions and graphs that
      are applicable for quantification of rate and extent of tolerance and rebound.
      The dynamics of the moderators (k(tol)) compared to the dynamics of the response
      (k(out)), was shown to be important for the behaviour of both systems. For
      instance, slow dynamics of the moderator compared to the response
      (k(tol)<<k(out)), resulted in overshoot and pronounced rebound. The extent of
      tolerance was studied over time at a single constant drug concentration and at
      steady state for different drug concentrations and was found to be largest at
      drug concentrations close to IC(50). An upper limit for the response could be
      identified and included in the quantification of extent of rebound. Especially,
      for the extended system, the duration of exposure was an important factor
      affecting size of rebound. The rate of tolerance development was addressed by
      quantitatively estimating the time to steady state for the two systems, in which
      the value of k(tol) and the length of the cascade were critical.

PMID- 21856417
TI  - Partial amplitude synchronization detection in brain signals using Bayesian
      Gaussian mixture models.
AB  - The present work investigates instantaneous synchronization in multivariate
      signals. It introduces a new method to detect subsets of synchronized time series
      that do not consider any baseline information. The method is based on a Bayesian
      Gaussian mixture model applied at each location of a time-frequency map. The work
      assesses the relevance of detected subsets by a stability measure. The
      application to Local Field Potentials measured during a visuo-motor experiment in
      monkeys reveals a subset of synchronized time series measured in the visual
      cortex.

PMID- 21856418
TI  - Sex steroid receptors in human lung diseases.
AB  - Several epidemiological studies have reported that gender differences exist in
      clinical and biological manifestations of human lung diseases. In particular,
      women are far more likely to develop both neoplastic and non-neoplastic lung
      diseases than men. This gender difference above suggests that sex steroid may be
      involved in the pathogenesis of various lung diseases. These sex steroids mediate
      their effects through sex steroid receptors including estrogen receptors (ER)
      i.e. ERalpha and ERbeta progesterone receptors (PR) i.e. PR-A and PR-B and
      androgen receptors (ARs), all of which have been reported to be expressed in lung
      tissue. Therefore it becomes important to clarify the potential roles of sex
      steroid receptor in both neoplastic and non-neoplastic lung diseases toward
      improved treatment options for the patients. In this review, we summarized a
      number of studies in humans and experimental animals that have identified
      possible roles of sex steroids in respiratory physiology and pathology.

PMID- 21856419
TI  - Androgen dependent transcription of a mouse prostatic protein gene, PSP94:
      involvement of estrogen receptors.
AB  - Prostatic secretory protein 94 (PSP94) is a prostatic protein found in both
      humans and rodents. As with other prostatic proteins, expression of this protein
      is regulated by androgens. In order to understand the androgen-responsive
      transcriptional regulation mechanisms involved, the present study aimed to
      identify and characterize the promoter activity of the gene. The 5'flanking (5'f)
      region of mouse PSP94 (mPSP94) gene was cloned and introduced into a vector
      upstream of the luciferase reporter gene. A Chinese hamster ovarian cell line,
      CHO, and a human prostate adenocarcinoma cell line, LNCaP, were transiently
      transfected with our reporter constructs along with an androgen receptor
      expression vector, and treated with dihydrotestosterone. Reporter gene assay
      revealed that the 5'f region of mPSP94 gene was indeed responsible for the
      androgen-dependent transcription. Subsequent deletion and mutation analysis
      indicated that the androgen responsive element (ARE)-like sequence at position 
      93 from the transcription start site was primarily responsible for androgen
      dependency. Interestingly, when estrogen receptor (ER) alpha was co-transfected,
      the androgen-dependent transcription was substantially increased. However,
      ERalpha-dependent enhancement of androgen responses was not observed when
      estrogen responsive element (ERE)-like motifs of the promoter region were
      deleted. Administration of estrogen did not influence the enhancement associated
      with ERalpha, although an anti-estrogen suppressed such effects. Collectively,
      these data suggest that the androgen-dependent transcription of the mPSP94 gene
      was co-regulated/modulated by the presence of ERalpha via ERE-like motifs.

PMID- 21856420
TI  - Efficient peripheral construction of functional human regulatory
      CD4(+)CD25(high)Foxp3(+) T cells in NOD/SCID mice grafted with fetal human
      thymus/liver tissues and CD34(+) cells.
AB  - Regulatory T cells, especially CD4(+)CD25(+) regulatory T cells are critical
      regulators of immune tolerance in humans and mice. Mice with humanized immunity
      have been developed by various transplantation strategies of human tissues or
      cells related to immunity, which are being extensively applied in biomedical
      research. However, it is unclear whether human CD4(+)CD25(+) regulatory T cells
      can normally develop in human thymic grafts and efficiently populate in the
      periphery in NOD/SCID mouse recipients. In human thymic grafts, high percentage
      of mature human CD4(+)CD25(high) regulatory T cells was detected. Human
      CD4(+)CD25(+) regulatory T cells maturing in fetal human thymus grafts could
      subsequently output to the periphery of NOD/SCID mouse recipients. Importantly,
      these cells exhibited Foxp3(+)CD45RO(+)CTLA4(+)CD127(-) phenotype, similarly to
      those in healthy individuals. In addition, human CD4(+)CD25(+) regulatory T cells
      maturing in human thymic grafts suppressed proliferative response of CD4(+)CD25(
      ) T cells to allogeneic antigens, though the peripheral CD4(+)CD25(+) regulatory
      T cells in fetal human thymus-grafted NOD/SCID mice showed somewhat decreased
      immunosuppressive ability compared with normal CD4(+)CD25(+) regulatory T cells.
      Thus, this humanized animal model is suitable for examining development and
      function of human CD4(+)CD25(+) regulatory T cells in vivo.

PMID- 21856421
TI  - Roles of vascular endothelial growth factor in acute rejection reaction following
      liver transplantation.
AB  - The presently known cytokines that participate in acute rejection of organ
      transplantation include four categories by order of function: inflammatory
      cytokines, immunospecific cytokines, inflammatory cell activating cytokines and
      growth cytokines. Of them, growth cytokines that directly induce division,
      proliferation and migration of endothelial cells mainly include the vascular
      endothelial growth factor (VEGF) family and the fibroblast growth factor (FGF)
      family [1]. Recent studies [2] showed that interactions and time overlap of
      inflammatory cell infiltration and angiogenesis are the main mechanisms that
      induce acute rejection (AR) following organ transplantation, which has been
      demonstrated by the clinical fact that AR symptoms after liver transplantation
      could only be relieved by combination use of drugs for improving micro vessels
      and those for improving micro bile ducts. This article is a review of VEGF that
      mediates inflammatory cell infiltration and angiogenesis in the portal area [3].

PMID- 21856422
TI  - Arsenic trioxide is a novel agent for combination therapy to prolong heart
      allograft survival in allo-primed T cells transferred mice.
AB  - Alloreactive memory T cells are major barriers to transplantation acceptance due
      to their capacity to accelerate rejection. Here, we investigated the effects of
      combined treatment with arsenic trioxide (As(2)O(3)) and blocking monoclonal
      antibodies (mAb) against CD154 and LFA-1 (anti-CD154/LFA-1) on graft survival as
      well as changes in pathology and immunological responses in mice with adoptively
      transferred allo-primed T cells. The mean survival time (MST) for the cardiac
      allografts in recipient mice receiving the combination of As(2)O(3) and anti
      CD154/LFA-1 was significantly longer (>113.7days) compared to those receiving
      anti-CD154/LFA-1 (23.2days), As(2)O(3) (12.5days) alone or no treatment
      (5.5days). This combined strategy distinctly inhibited lymphocyte infiltration in
      grafts, proliferation of splenic T cells and the generation of memory T cells in
      spleens. Moreover, the combined treatment caused the significant down-regulation
      of IL-2 and IFN-gamma accompanied by increased expression of TGF-beta and
      regulatory T cells (Tregs) in spleens, which led to long-term cardiac allograft
      survival in recipient mice. These results highlight the potential application of
      As(2)O(3) and its contribution in combination therapy with antibody blockade to
      delay rejection by memory T cells.

PMID- 21856423
TI  - Altered expression of brain monocarboxylate transporter 1 in models of temporal
      lobe epilepsy.
AB  - Monocarboxylate transporter 1 (MCT1) facilitates the transport of monocarboxylate
      fuels (lactate, pyruvate and ketone bodies) and acidic drugs, such as valproic
      acid, across cell membranes. We recently reported that MCT1 is deficient on
      microvessels in the epileptogenic hippocampal formation in patients with
      medication-refractory temporal lobe epilepsy (TLE). To further define the role of
      MCT1 in the pathophysiology of TLE, we used immunohistochemistry and
      stereological analysis to localize and quantify the transporter in the
      hippocampal formation in three novel and highly relevant rat models of TLE and in
      nonepileptic control animals. One model utilizes methionine sulfoximine to induce
      brain glutamine synthetase deficiency and recurrent limbic seizures, while two
      models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1
      was lost on microvessels and upregulated on astrocytes in the hippocampal
      formation in all models of TLE. Notably, the loss of MCT1 on microvessels was not
      due to a reduction in microvessel density. The similarities in MCT1 expression
      among human subjects with TLE and several animal models of the disease strongly
      suggest a critical role of this molecule in the pathogenesis of TLE. We
      hypothesize that the downregulation of MCT1 may promote seizures via impaired
      uptake of ketone bodies and antiepileptic drugs by the epileptogenic brain. We
      also propose that the overexpression of MCT1 on astrocytes may lead to increased
      uptake or release of monocarboxylates by these cells, with important implications
      for brain metabolism and excitability. These hypotheses can now be rigorously
      tested in several animal models that replicate key features of human TLE.

PMID- 21856424
TI  - Post mortem cerebrospinal fluid alpha-synuclein levels are raised in multiple
      system atrophy and distinguish this from the other alpha-synucleinopathies,
      Parkinson's disease and Dementia with Lewy bodies.
AB  - Differentiating clinically between Parkinson's disease (PD) and the atypical
      parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal
      syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for
      patient management and recruitment into clinical trials. Because PD (and the
      related disorder Dementia with Lewy bodies (DLB)) and MSA are characterised by
      the deposition of aggregated forms of alpha-synuclein protein (alpha-syn) in the
      brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to
      detect levels of total and oligomeric forms of alpha-syn, and phosphorylated and
      phosphorylated oligomeric forms of alpha-syn, within body fluids, in an attempt
      to find a biomarker that will differentiate between these disorders. Levels of
      these 4 different forms of alpha-syn were measured in post mortem samples of
      ventricular cerebrospinal fluid (CSF) obtained from 76 patients with PD, DLB, PSP
      or MSA, and in 20 healthy controls. Mean CSF levels of total and oligomeric alpha
      syn, and phosphorylated alpha-syn, did not vary significantly between the
      diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric alpha-syn
      did differ significantly (p<0.001) amongst the different diagnostic groups.
      Although all 4 measures of alpha-syn were higher in patients with MSA compared to
      all other diagnostic groups, these were only significantly raised (p<0.001) in
      MSA compared to all other diagnostic groups, for phosphorylated oligomeric forms
      of alpha-syn. This suggests that this particular assay may have utility in
      differentiating MSA from control subject and patients with other alpha
      synucleinopathies. However, it does not appear to be of help in distinguishing
      patients with PD and DLB from those with PSP or from control subjects. Western
      blots show that the principal form of alpha-syn within CSF is phosphorylated, and
      the finding that the phosphorylated oligomeric alpha-syn immunoassay appears to
      be the most informative of the 4 assays would be consistent with this
      observation.

PMID- 21856425
TI  - Neuromodulatory role of endogenous interleukin-1beta in acute seizures: possible
      contribution of cyclooxygenase-2.
AB  - The function of endogenous interleukin-1beta (IL-1beta) signaling in acute
      seizure activity was examined using transgenic mice harboring targeted deletions
      in the genes for either IL-1beta (Il1b) or its signaling receptor (Il1r1). Acute
      epileptic seizure activity was modeled using two mechanistically distinct
      chemoconvulsants, kainic acid (KA) and pentylenetetrazole (PTZ). KA-induced
      seizure activity was more severe in homozygous null (-/-) Il1b mice compared to
      their wild-type (+/+) littermate controls, as indicated by an increase in the
      incidence of sustained generalized convulsive seizure activity. In the PTZ
      seizure model, the incidence of acute convulsive seizures was increased in both
      Il1b and Il1r1-/- mice compared to their respective +/+ littermate controls.
      Interestingly, the selective cyclooxygenase (COX)-2 inhibitor, rofecoxib,
      mimicked the effect of IL-1beta deficiency on PTZ-induced convulsions in Il1r1+/+
      but not -/- mice. Together, these results suggest that endogenous IL-1beta
      possesses anticonvulsive properties that may be mediated by arachidonic acid
      metabolites derived from the catalytic action of COX-2.

PMID- 21856427
TI  - High throughput construction and small scale expression screening of multi-tag
      vectors in Escherichia coli.
AB  - A suite of protein fusion vectors is presented that has been designed so that
      nine separate fusion vectors can be constructed from one PCR product using
      InFusionTM cloning. These vectors in combination with a small scale Escherichia
      coli expression screen can be used to assess in parallel the effect of fusion
      tags on solubility. The vectors were tested with 20 target proteins and the
      results suggest that the vectors are useful both as a rescue strategy if the N
      terminal hexa-histidine tagged construct does not express and also as part of a
      primary expression experiment.

PMID- 21856428
TI  - Optimized refolding and characterization of S-peroxidase (CWPO_C of Populus alba)
      expressed in E. coli.
AB  - Cationic cell wall peroxidase (CWPO_C) from poplar tree (Populus alba L) was
      heterologously expressed in Escherichia coli as an inclusion body. The insoluble
      inclusion body was solubilized and reactivated via a refolding procedure. The
      condition for this procedure was optimized by varying the refolding pH, and the
      concentrations of the oxidizing agent (GSSG), denaturing agent (GndCl), and
      hemin, respectively. The optimal conditions for refolding CWPO_C were 100 mM Tris
      HCl at pH 8.5, 0.6mM GSSG, 5 MUM hemin, 0.6 M GndCl and 5 mM CaCl2. The fact that
      the absorbance spectrum was identical to that of wild CWPO_C from poplar tree
      suggests that the protein folding, heme insertion and iron coordination were
      correctly archived. The binding affinity and turnover rate values of refolded
      CWPO_C were compared with those of HRP_C. k(cat)/K(m) for sinapyl alcohol of
      CWPO_C was over 170 times higher than that of HRP_C, on the while k(cat)/K(m) for
      coniferyl alcohol showed similar values for both peroxidase. The kinetic
      parameters showed that refolded CWPO_C possesses a very unique property of S
      peroxidase, preferentially oxidizes sinapyl alcohol rather than coniferyl
      alcohol. The successful expression of CWPO_C in E. coli provides a valuable tool
      to elucidate the structure and functional relationship of S-peroxidase, which
      plays an important role in the lignification of angiosperm woody plant cell
      walls.

PMID- 21856426
TI  - Dynamic changes in Wnt signaling are required for neuronal differentiation of
      mouse embryonic stem cells.
AB  - Embryonic stem cells (ESC) and the epiblast share a similar gene expression
      profile and an attenuated cell cycle, making them an accessible and tractable
      model system to study lineage choice at gastrulation. Differentiation of the
      epiblast and ESC to the mesendodermal lineage has been shown to rely on Wnt/beta
      catenin signaling; which counterintuitively, is also required to inhibit
      differentiation and maintain pluripotency. To examine these seemingly
      contradictory roles, we developed a mouse ESC (ESC) line that inducibly expresses
      a dominant negative Tcf4 (dnTcf4) protein to block canonical Wnt signaling. Cells
      expressing the dnTcf4 protein differentiated largely to Sox3 positive neural
      precursors but were unable to progress to betaIII tubulin positive neurons unless
      Wnt signaling was derepressed, demonstrating a sequential requirement for Wnt
      signaling in lineage differentiation. To determine if Wnt/beta-catenin signaling
      is similarily required at sequential stages of neural differentiation in the
      intact embryo, we delivered shRNA targeting beta-catenin to pregnant mice on E5.5
      of development. Blocking canonical Wnt signaling during post-implantation
      development increased the number of neural precursors which failed to
      differentiate to mature neurons, and produced defects of embryonic axis
      elongation, neurulation and neural tube closure that phenocopy the beta-catenin
      null embryo. These results demonstrate that lineage differentiation relies on
      sequential repression and derepression of critical signaling pathways involved in
      maintaining pluripotency versus differentiation.

PMID- 21856429
TI  - Moderators of the association between brain activation and farsighted choice.
AB  - There is equivocal support for the hypothesis that preference for later larger
      (LL) over sooner smaller (SS) monetary alternatives (e.g., $50 in four months
      over $30 today) is associated with functioning of the insula and the prefrontal
      cortex (especially the lateral PFC). In the present study, we re-examined overall
      neural correlates of choice using a procedure to minimize potential confounds
      between choice (which is necessarily not under experimental control) and
      valuation. In addition, we assessed whether choice-related brain activity is
      moderated by 1) overall level of delay discounting and 2) the degree of
      stochasticity in individuals' intertemporal choices. Twenty-one participants
      completed an individualized intertemporal choice task while brain activity was
      measured using functional Magnetic Resonance Imaging (fMRI). Across participants,
      LL choice was associated with activity in left dorsolateral prefrontal cortex
      (dlPFC), left insula/inferior frontal gyrus (IFG), frontal pole and the anterior
      cingulate cortex (ACC). Stochasticity positively moderated the LL>SS activity
      within the left insula and left IFG. Degree of discounting also interacted with
      choice related activity, but only outside the LL vs. SS main effect map (in the
      posterior cingulate cortex, and precentral/postcentral gyrus and left dlPFC).
      Main effect results are consistent with the notion that lateral prefrontal
      activity during intertemporal decisions bias selection in the direction of LL.
      Correlation findings indicate that choice related activity in the left insula and
      IFG is moderated by the stochasticity of intertemporal choices, and may reflect
      reduced "executive function" demands among highly consistent participants.

PMID- 21856430
TI  - fMRI of pain processing in the brain: a within-animal comparative study of BOLD
      vs. CBV and noxious electrical vs. noxious mechanical stimulation in rat.
AB  - This study aims to identify fMRI signatures of nociceptive processing in whole
      brain of anesthetized rats during noxious electrical stimulation (NES) and
      noxious mechanical stimulation (NMS) of paw. Activation patterns for NES were
      mapped with blood oxygen level dependent (BOLD) and cerebral blood volume (CBV)
      fMRI, respectively, to investigate the spatially-dependent hemodynamic responses
      during nociception processing. A systematic evaluation of fMRI responses to
      varying frequencies of electrical stimulus was carried out to optimize the NES
      protocol. Both BOLD and CBV fMRI showed widespread activations, but with
      different spatial characteristics. While BOLD and CBV showed well-localized
      activations in ipsilateral dorsal column nucleus, contralateral primary
      somatosensory cortex (S1), and bilateral caudate putamen (CPu), CBV fMRI showed
      additional bilateral activations in the regions of pons, midbrain and thalamus
      compared to BOLD fMRI. CBV fMRI that offers higher sensitivity compared to BOLD
      was then used to compare the nociception processing during NES and NMS in the
      same animal. The activations in most regions were similar. In the medulla,
      however, NES induced a robust activation in the ipsilateral dorsal column nucleus
      while NMS showed no activation. This study demonstrates that (1) the hemodynamic
      response to nociception is spatial-dependent; (2) the widespread activations
      during nociception in CBV fMRI are similar to what have been observed in (14)C-2
      deoxyglucose (2DG) autoradiography and PET; (3) the bilateral activations in the
      brain originate from the divergence of neural responses at supraspinal level; and
      (4) the similarity of activation patterns suggests that nociceptive processing in
      rats is similar during NES and NMS.

PMID- 21856431
TI  - The future of fMRI in cognitive neuroscience.
AB  - Over the last 20 years, fMRI has revolutionized cognitive neuroscience. Here I
      outline a vision for what the next 20 years of fMRI in cognitive neuroscience
      might look like. Some developments that I hope for include increased
      methodological rigor, an increasing focus on connectivity and pattern analysis as
      opposed to "blobology", a greater focus on selective inference powered by open
      databases, and increased use of ontologies and computational models to describe
      underlying processes.

PMID- 21856432
TI  - A simple and inexpensive method to fabricate a cannula system for intracranial
      injections in rats and mice.
AB  - INTRODUCTION: Stereotaxic administration of neuroactive agents, either in
      ventricles, or targeted at specific intracranial sites, is a widely employed
      strategy for neurological studies in rodents. Surgical implantation of cannula on
      the skull is particularly useful in chronic treatments. We describe a simple,
      inexpensive and reliable method to fabricate a cannula system for delivery of
      drugs at the targeted sites in the brain of rat or mouse. METHODS: The system
      consists of a guide cannula made from a hypodermic needle (24 gauge), a stainless
      steel wire (30 gauge) that serves as a dummy cannula, and an internal cannula
      made of stainless steel needle (30 gauge) taken from a hypodermic syringe. The
      cannula can be implanted by routine stereotaxic procedure and used for acute or
      chronic drug administration to conscious, free moving animals. RESULTS: With a
      view to test the system for accuracy, the guide cannula was stereotaxically
      implanted, and neuropeptide Y was directly delivered into the lateral ventricle.
      These rats showed a significant increase in food intake. Another set of rats were
      cannulated for chronic protocol, wherein ethanol was delivered directly into the
      ventral tegmental area. In operant chamber, these rats showed increased ethanol
      self-administration. The proposed cannula takes around 5 min to fabricate and
      costs less than a dollar. CONCLUSION: We feel that it may serve as an economical
      and reliable tool in neuropharmacological and neurobehavioral studies.

PMID- 21856434
TI  - The influence of oocyte cortisol on the early ontogeny of intelectin and TLR-5,
      and changes in lysozyme activity in rainbow trout (Oncorhynchus mykiss) embryos.
AB  - The ontogeny of lysozyme activity, intelectin, TLR-5M and TLR-5S gene expression
      and intelectin localization was examined in rainbow trout (Oncorhynchus mykiss)
      reared from oocytes immersed for 3h prior to fertilization in either ovarian
      fluid alone (CC) or cortisol-enriched ovarian fluid at either 100 ng mL(-1) (C1)
      or 1000 ng mL(-1) (C2) [final oocyte cortisol concentrations were ~3, ~5, and
      ~7.5 ng oocyte(-1) for the CC, C1 and C2 treatment groups, respectively].
      Lysozyme activity was elevated in the cortisol-treated groups from the zygote
      until 13-days post fertilization (dpf), but was not affected at 21-dpf.
      Intelectin levels were elevated in both cortisol treatment groups at 12-hpf (2
      cell stage) and then suppressed between 36- and 48-hpf. Intelectin mRNA
      transcript levels were elevated in both cortisol treatment groups in oocytes;
      there were no differences among treatment groups at 1- and 5-dpf, and suppressed
      in the C2 treatment group in 13-dpf and 26-dpf. TLR-5 mRNA transcripts were
      higher in cortisol-treated oocytes prior to fertilization; TLR-5S mRNA was more
      abundant than TLR-5M mRNA. The ontogeny of the gene expression patterns, and the
      gene, lectin and lysozyme responses to oocyte cortisol adjustments suggest an
      important role of innate immune systems in the early cleavage stages of embryonic
      cells.

PMID- 21856433
TI  - AMPA receptor regulation during synaptic plasticity in hippocampus and neocortex.
AB  - Discovery of long-term potentiation (LTP) in the dentate gyrus of the rabbit
      hippocampus by Bliss and Lomo opened up a whole new field to study activity
      dependent long-term synaptic modifications in the brain. Since then hippocampal
      synapses have been a key model system to study the mechanisms of different forms
      of synaptic plasticity. At least for the postsynaptic forms of LTP and long-term
      depression (LTD), regulation of AMPA receptors (AMPARs) has emerged as a key
      mechanism. While many of the synaptic plasticity mechanisms uncovered in at the
      hippocampal synapses apply to synapses across diverse brain regions, there are
      differences in the mechanisms that often reveal the specific functional
      requirements of the brain area under study. Here we will review AMPAR regulation
      underlying synaptic plasticity in hippocampus and neocortex. The main focus of
      this review will be placed on postsynaptic forms of synaptic plasticity that
      impinge on the regulation of AMPARs using hippocampal CA1 and primary sensory
      cortices as examples. And through the comparison, we will highlight the key
      similarities and functional differences between the two synapses.

PMID- 21856435
TI  - 11,12-EET increases porto-sinusoidal resistance and may play a role in
      endothelial dysfunction of portal hypertension.
AB  - CYP450-dependent epoxyeicosatrienoic acids (EETs) are potent arterial
      vasodilators, while 20-hydroxyeicosatatraenoic acid (20-HETE) is a
      vasoconstrictor. We evaluated their role in the control of portal circulation in
      normal and cirrhotic (CCl(4) induced) isolated perfused rat liver. Phenylephrine
      (PE) and endothelin-1 (ET-1) increased portal perfusion pressure, as did
      arachidonic acid (AA), 20-HETE, and 11,12-EET. Inhibition of 20-HETE with 12,12
      dibromododecenoic acid (DBDD) did not affect basal pressure nor the responses to
      PE, ET-1, or AA. However, inhibition of epoxygenase with miconazole caused a
      significant reduction in the response to ET-1 and to AA, without affecting
      neither basal pressure nor the response to PE. Hepatic vein EETs concentration
      increased in response to ET-1, and was increased in cirrhotic, compared to
      control, livers. 20HETE levels were non-measurable. Miconazole decreased portal
      perfusion pressure in cirrhotic livers. In conclusion, 20HETE and EETs increase
      portal resistance; EETs, but not 20-HETE, mediate in part the pressure response
      to ET-1 in the portal circulation and may be involved in pathophysiology of
      portal hypertension.

PMID- 21856436
TI  - The role of chitin detection in plant--pathogen interactions.
AB  - Despite the deployment of antifungal defence strategies, fungal diseases occur in
      all types of multicellular organisms. In plants, the role of fungal chitin as
      pathogen-associated molecular pattern that activates host defence is well
      established. Interestingly, plants employ homologs of the chitin immune receptors
      to initiate microbial symbiosis. Accumulating evidence shows that fungal
      pathogens developed secreted effectors to disarm chitin-triggered host immunity.

PMID- 21856437
TI  - Different roles of p53 in the regulation of DNA damage caused by 1,2
      heteroannelated anthraquinones and doxorubicin.
AB  - The anthracyclin antibiotic agent doxorubicin (DXR) has been widely used as a
      chemotherapeutic drug for more than 40 years, but its clinical use has been
      limited by its cardiotoxicity. The mechanism of action of DXR remains uncertain
      and controversial. A series of 1,2-heteroannelated anthraquinones and anthra[1,2
      d]imidazole-6,11-dione compounds were synthesized and their cytotoxicity profiles
      were analyzed using the National Cancer Institute 60 (NCI 60) platform and human
      telomerase inhibition assays. In the current study, three of the 1,2
      heteroannelated anthraquinones, NSC745795, NSC745885 and NSC745887, were found to
      differ from each other with respect to their effects on cell cycle regulation,
      apoptosis, autophagy, senescence and their abilities to induce DNA damage. The
      differences depended on the presence or absence of a heterocyclic moiety, which
      suggested that the differences were due, at least in part, to differential
      effects on specific cellular targets, such as p53. In contrast to DXR, which
      induced p53 expression, treatment with NSC745885 resulted in the degradation of
      several proteins, including p53, via proteasome-dependent and -independent
      pathways in HeLa cells. These results provide insights into the molecular
      mechanisms governing cell inhibition by 1,2-heteroannelated anthraquinone
      derivatives and suggest that these mechanisms could serve as the basis for new
      structure-based drug designs.

PMID- 21856438
TI  - The regulatory framework of biosimilars in the European Union.
AB  - In the European Union (EU), the regulatory policy for biosimilars has enabled
      different biosimilar products to be marketed through an abridged application,
      which allows the applicant to submit a reduced dossier. Nevertheless, some
      manufacturers of biological products that share some characteristics with copies
      have opted for a full application; therefore, the number and extent of clinical
      studies required in these cases is increased. Here, we focus on a comparison of
      recombinant human erythropoietin medicinal products. We analyse and discuss
      clinical studies submitted to the European Medicines Agency that relate to
      available biosimilars and biological medicinal products that are authorised with
      a full dossier. We also discuss the issues of interchangeability and
      substitution, given that the EU allows each Member State to set their own
      substitution policies.

PMID- 21856439
TI  - First monogenean flatworm from a microhylid frog host: Kankana, a new polystome
      genus from Madagascar.
AB  - Kankana manampoka n. gen., n. sp. (Monogenea, Polystomatidae), is described from
      the urinary bladder of the narrow-mouthed frog Platypelis pollicaris. This is the
      first record of a polystome from the Microhylidae and the third polystome genus
      from Madagascar, next to Metapolystoma and Madapolystoma. The extensive uterus
      and presence of hamuli resemble Metapolystoma but the vitellarium confined to the
      lateral fields in Kankana is different. Madapolystoma also has an extensive
      uterus but contain only up to 32 advanced developed larvae. Based on the
      extensive uterus filling the body proper and the vitellarium confined to two
      lateral fields posterior in the body this new polystome resembles Eupolystoma
      known from Africa and India. However, unlike Eupolystoma, the gonads are in the
      middle of the body, vaginae are lacking and a pair of hamuli is present. A
      molecular phylogenetic analysis of concatenated 18S and 28S ribosomal RNA gene
      sequences supplemented by genetic distances inferred from 28S and COI sequences
      showed that this new genus is more related to Madapolystoma, a genus only
      reported from Madagascar, than to Eupolystoma known from Africa and India and
      Metapolystoma known from Africa and Madagascar.

PMID- 21856440
TI  - Applying semantic-based probabilistic context-free grammar to medical language
      processing--a preliminary study on parsing medication sentences.
AB  - Semantic-based sublanguage grammars have been shown to be an efficient method for
      medical language processing. However, given the complexity of the medical domain,
      parsers using such grammars inevitably encounter ambiguous sentences, which could
      be interpreted by different groups of production rules and consequently result in
      two or more parse trees. One possible solution, which has not been extensively
      explored previously, is to augment productions in medical sublanguage grammars
      with probabilities to resolve the ambiguity. In this study, we associated
      probabilities with production rules in a semantic-based grammar for medication
      findings and evaluated its performance on reducing parsing ambiguity. Using the
      existing data set from 2009 i2b2 NLP (Natural Language Processing) challenge for
      medication extraction, we developed a semantic-based CFG (Context Free Grammar)
      for parsing medication sentences and manually created a Treebank of 4564
      medication sentences from discharge summaries. Using the Treebank, we derived a
      semantic-based PCFG (Probabilistic Context Free Grammar) for parsing medication
      sentences. Our evaluation using a 10-fold cross validation showed that the PCFG
      parser dramatically improved parsing performance when compared to the CFG parser.

PMID- 21856441
TI  - Coreference resolution: a review of general methodologies and applications in the
      clinical domain.
AB  - Coreference resolution is the task of determining linguistic expressions that
      refer to the same real-world entity in natural language. Research on coreference
      resolution in the general English domain dates back to 1960s and 1970s. However,
      research on coreference resolution in the clinical free text has not seen major
      development. The recent US government initiatives that promote the use of
      electronic health records (EHRs) provide opportunities to mine patient notes as
      more and more health care institutions adopt EHR. Our goal was to review recent
      advances in general purpose coreference resolution to lay the foundation for
      methodologies in the clinical domain, facilitated by the availability of a shared
      lexical resource of gold standard coreference annotations, the Ontology
      Development and Information Extraction (ODIE) corpus.

PMID- 21856442
TI  - Toward automated consumer question answering: automatically separating consumer
      questions from professional questions in the healthcare domain.
AB  - OBJECTIVE: Both healthcare professionals and healthcare consumers have
      information needs that can be met through the use of computers, specifically via
      medical question answering systems. However, the information needs of both groups
      are different in terms of literacy levels and technical expertise, and an
      effective question answering system must be able to account for these differences
      if it is to formulate the most relevant responses for users from each group. In
      this paper, we propose that a first step toward answering the queries of
      different users is automatically classifying questions according to whether they
      were asked by healthcare professionals or consumers. DESIGN: We obtained two sets
      of consumer questions (~10,000 questions in total) from Yahoo answers. The
      professional questions consist of two question collections: 4654 point-of-care
      questions (denoted as PointCare) obtained from interviews of a group of family
      doctors following patient visits and 5378 questions from physician practices
      through professional online services (denoted as OnlinePractice). With more than
      20,000 questions combined, we developed supervised machine-learning models for
      automatic classification between consumer questions and professional questions.
      To evaluate the robustness of our models, we tested the model that was trained on
      the Consumer-PointCare dataset on the Consumer-OnlinePractice dataset. We
      evaluated both linguistic features and statistical features and examined how the
      characteristics in two different types of professional questions (PointCare vs.
      OnlinePractice) may affect the classification performance. We explored
      information gain for feature reduction and the back-off linguistic category
      features. RESULTS: The 10-fold cross-validation results showed the best F1
      measure of 0.936 and 0.946 on Consumer-PointCare and Consumer-OnlinePractice
      respectively, and the best F1-measure of 0.891 when testing the Consumer
      PointCare model on the Consumer-OnlinePractice dataset. CONCLUSION: Healthcare
      consumer questions posted at Yahoo online communities can be reliably classified
      from professional questions posted by point-of-care clinicians and online
      physicians. The supervised machine-learning models are robust for this task. Our
      study will significantly benefit further development in automated consumer
      question answering.

PMID- 21856443
TI  - The infra-red (IR) landscape of Triatoma infestans. An hypothesis about the role
      of IR radiation as a cue for Triatominae dispersal.
AB  - This paper presents the infrared (IR) emission spectrum of hosts and habitats of
      Triatoma infestans in the chaco region of NW Argentina, representing the first
      attempt to correlate the natural infrared stimulus with the known behaviour of
      these blood-sucking insect, vectors of Trypanosoma cruzi--causative agent of
      Chagas disease. The study was carried out in two rural villages of La Rioja
      Province (Argentina). A FLYR i40 camera was used to obtain IR pictures which were
      analyzed to determine the thermal range for humans, domestic animals, building
      materials, and general background emissions. From sunset to the first hours of
      night, the thermal contrast between hosts and their landscape rises, increasing
      the likelihood that hosts could be differentiated by the vector. However, some
      building materials, can retain high temperatures during the night, which might
      add attractiveness to the presence of hosts. The results suggest that the most
      attractive habitats for dispersing bugs would be those at short distance, with
      high CO2 emission and strong IR radiation indicative of host presence. Goats
      corrals may be the most attractive habitat to disperse, within the domestic
      habitat. Dispersal would be favoured in periods of low atmospheric water
      saturation when IR perception is highest. In the IR band, the potential host and
      habitat discrimination available for the insects fits well with their known
      sensory capacities and observed dispersive behavior. Research in this area could
      be of considerable interest in relation to vector surveillance, epidemiology of
      Chagas disease transmission, and to develop new methods to minimise triatomine
      colonisation of new habitats.

PMID- 21856444
TI  - Genetic characterization of flea-derived Bartonella species from native animals
      in Australia suggests host-parasite co-evolution.
AB  - Fleas are important arthropod vectors for a variety of diseases in veterinary and
      human medicine, and bacteria belonging to the genus Bartonella are among the
      organisms most commonly transmitted by these ectoparasites. Recently, a number of
      novel Bartonella species and novel species candidates have been reported in
      marsupial fleas in Australia. In the present study the genetic diversity of
      marsupial fleas was investigated; 10 species of fleas were collected from seven
      different marsupial and placental mammal hosts in Western Australia including
      woylies (Bettongia penicillata), western barred bandicoots (Perameles
      bougainville), mardos (Antechinus flavipes), bush rats (Rattus fuscipes), red
      foxes (Vulpes vulpes), feral cats (Felis catus) and rabbits (Oryctolagus
      cuniculus). PCR and sequence analysis of the cytochrome oxidase subunit I (COI)
      and the 18S rRNA genes from these fleas was performed. Concatenated phylogenetic
      analysis of the COI and 18S rRNA genes revealed a close genetic relationship
      between marsupial fleas, with Pygiopsylla hilli from woylies, Pygiopsylla tunneyi
      from western barred bandicoots and Acanthopsylla jordani from mardos, forming a
      separate cluster from fleas collected from the placental mammals in the same
      geographical area. The clustering of Bartonella species with their marsupial flea
      hosts suggests co-evolution of marsupial hosts, marsupial fleas and Bartonella
      species in Australia.

PMID- 21856445
TI  - Laminarin, a soluble beta-glucan, inhibits macrophage phagocytosis of zymosan but
      has no effect on lipopolysaccharide mediated augmentation of phagocytosis.
AB  - Phagocytosis is a fundamental aspect of innate resistance against microbes,
      including fungi. In this study we investigated the significance of beta-glucan on
      the surfaces of zymosan particles, derived from Saccharomyces cerevisiae, during
      phagocytosis by RAW 264.7 macrophages. Phagocytosis was assessed in vitro by
      macrophage exposure to zymosan particles followed by cell staining and light
      microscopy. Macrophage ingestion of zymosan was dependent on cellular recognition
      of the particles' beta-glucans since laminarin, a soluble beta-glucan, inhibited
      phagocytosis in a concentration dependent manner when added to cell cultures. In
      contrast, the presence of another carbohydrate, mannan, had no effect on zymosan
      phagocytosis by cells. In addition we showed that LPS and dexamethasone had
      opposing effects on phagocytosis of zymosan. LPS significantly augmented
      ingestion while in contrast dexamethasone, like laminarin, suppressed it. The LPS
      enhanced ingestion of zymosan was insensitive to the presence of laminarin in
      cell cultures, however dexamethasone partially ameliorated the effects of LPS on
      phagocytosis. Our findings confirm beta-glucan as an important ligand identified
      by macrophages and required for zymosan phagocytosis in naive cells, but not in
      cells previously exposed to LPS.

PMID- 21856447
TI  - Berberine inhibits the production of thymic stromal lymphopoietin by the blockade
      of caspase-1/NF-kappaB pathway in mast cells.
AB  - Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases
      such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease.
      However, it has not been clarified the effect of berberine (BER) on the
      production of TSLP yet. Thus, we investigated how BER inhibits the production of
      TSLP in the human mast cell line (HMC-1) cells. We used enzyme-linked
      immunosorbent assay, reverse transcription-polymerase chain reaction, luciferase
      assay, and Western blot analysis to investigate the effects of BER. BER inhibited
      the production and mRNA expression of TSLP in HMC-1 cells. BER also inhibited the
      nuclear factor-kappaB luciferase activity induced by phorbol myristate acetate
      plus A23187. BER inhibited the activation of caspase-1 in HMC-1 cells.
      Furthermore, BER inhibited the production of TSLP in primary mast cells. These
      results provide evidence that BER can help to treat inflammatory and atopic
      diseases through the inhibition of TSLP.

PMID- 21856448
TI  - A novel mitotropic oligolysine nanocarrier: Targeted delivery of covalently bound
      D-Luciferin to cell mitochondria.
AB  - New and emerging therapeutic approaches focus on the targeted delivery of
      therapeutic agents to cell mitochondria with high specificity. Herein we present
      a novel mitotropic nanocarrier based on an oligolysine scaffold by addition of
      two triphenylphosphonium cations per oligomer. Although the parent oligolysine
      failed to enter healthy cells, the triphenylphosphonium modified carrier, with or
      without D-Luciferin, attached as cargo molecule, demonstrated striking
      mitochondrial specificity. Furthermore, the oligolysine bound d-Luciferin
      exhibited chemiluminescence, of lower intensity than free d-Luciferin, yet of
      remarkably longer steady-state temporal profile.

PMID- 21856446
TI  - Inhibitory effect of cepharanthine on dendritic cell activation and function.
AB  - Dendritic cells (DCs) are specialized antigen presenting cells that connect
      innate and adaptive immunity. DCs are considered as a major target for
      controlling excessive immune responses. In this study, the effect of
      cepharanthine (CEP), a biscoclaurine alkaloid isolated from Stephania cepharantha
      Hayata, on murine DCs was examined in vitro. CEP inhibited antigen uptake by DCs
      at a concentration between 1 and 5 MUg/ml. Although CEP did not inhibit the
      expression of costimulatory molecules and major histocompatibility complex (MHC)
      class I in DCs, the compound inhibited lipopolysaccharide (LPS)-induced DC
      maturation determined by the expression of costimulatory molecules and MHC class
      I. In addition, CEP could reduce the production of interleukin-6 and tumor
      necrosis factor-alpha in LPS-stimulated DCs. DCs treated with CEP were found to
      be a poor stimulator of allogeneic T cell proliferation and interferon-gamma
      production from the cells. These results suggest that CEP may have great
      potential as an immunoregulatory agent against various autoimmune diseases and
      allergy.

PMID- 21856449
TI  - Are mitochondrial haplogroups associated with elite athletic status? A study on a
      Spanish cohort.
AB  - There is increasing evidence regarding the association between mitochondrial DNA
      (mtDNA) and aerobic capacity; however, whether mtDNA haplogroups are associated
      with the status of being an elite endurance athlete is more controversial. We
      compared the frequency distribution of mtDNA haplogroups among the following
      groups of Spanish (Caucasian) men: 102 elite endurance athletes (professional
      road cyclists, endurance runners), 51 elite power athletes (jumpers, throwers and
      sprinters), and 478 non-athletic controls. We observed a significant difference
      between endurance athletes and controls (Fisher exact test=17.89, P=0.015;
      Bonferroni's significant threshold=0.017), yet not between power athletes and
      controls (Fisher exact test=47.99, P=0.381) or between endurance and power
      athletes (Fisher exact test=5.53, P=0.597). We observed that the V haplogroup was
      overrepresented in endurance athletes (15.7%) compared with controls (7.5%) (odds
      ratio: 2.284; 95% confidence interval: 1.237, 4.322). In conclusion, our findings
      overall support the idea that mtDNA variations could be among the numerous
      contributors to the status of being an elite endurance athlete, whereas no
      association was found with elite power athletic status.

PMID- 21856450
TI  - Biochemical analysis of the G517V POLG variant reveals wild-type like activity.
AB  - The c.1550g->t mutation in the POLG gene causing the G517V substitution has been
      reported by many groups to be associated with a variety of mitochondrial
      diseases, including autosomal dominant and recessive forms of ataxia neuropathy,
      myopathy and microcephaly, progressive external ophthalmoplegia, diabetes,
      strokes, hypotonia, and epilepsy. However, the variable disease presentation and
      age of onset raises suspicion of its pathogenicity. Because of the varied
      reported associated symptoms and request from physicians to address the
      consequence of this mutation, we have carried out the biochemical analysis of the
      purified recombinant human DNA polymerase gamma protein harboring the G517V
      substitution. These analyses revealed that the G517V mutant enzyme retained 80
      90% of wild-type DNA polymerase activity, in addition to its functional
      interaction with the p55 accessory subunit. DNA binding by the mutant was also
      only slightly lower than the wild-type enzyme. Our data suggest that the G517V
      mutation by itself in pol gamma most likely does not have a role in mitochondrial
      disorders.

PMID- 21856451
TI  - Calcium-dependent mitochondrial extrusion in ciliated protozoa.
AB  - Here we demonstrate that ciliated protozoa can jettison mitochondria as intact
      organelles, releasing their contents to the extracellular space either in a
      soluble form, or in association with membrane vesicles at the cell periphery. The
      response is triggered by lateral clustering of GPI-anchored surface antigens, or
      by heat shock. In the first instance, extrusion is accompanied by elevated levels
      of intracellular calcium and is inhibited by Verapamil and BAPTA-AM arguing
      strongly for the involvement of calcium in triggering the response. Cells survive
      mitochondrial discharge raising the interesting possibility that extrusion is an
      early evolutionary adaptation to cell stress.

PMID- 21856452
TI  - Systematic appraisal of dementia guidelines for the management of behavioural and
      psychological symptoms.
AB  - BACKGROUND: Within the treatment of dementia, management of behavioural and
      psychological symptoms (BPSD) is a complex component. PURPOSE: We wanted to offer
      a pragmatic synthesis of existing specific practice recommendations for managing
      BPSD, based on agreement among systematically appraised dementia guidelines. DATA
      SOURCES: We conducted a systematic search in MEDLINE and guideline organisation
      databases, supplemented by a hand search of web sites. STUDY SELECTION: Fifteen
      retrieved guidelines were eligible for quality appraisal by the Appraisal of
      Guidelines Research and Evaluation instrument (AGREE), performed by 2 independent
      reviewers. DATA EXTRACTION: From the 5 included guidelines, 18 specific practice
      recommendations for BPSD were extracted and compared for their level of evidence
      and strength. DATA SYNTHESIS: No agreement was found among dementia guidelines
      for the majority of specific practice recommendations with regard to non
      pharmacological interventions, although these were recommended as first-line
      treatment. Pharmacological specific practice recommendations were proposed as
      second-line treatment, with agreement for the use of a selection of
      antipsychotics based on strong supporting evidence, but with guidance for timely
      discontinuation. LIMITATIONS: The appraisal of the level of agreement between
      guidelines for each specific practice recommendation was complicated by variation
      in grading systems, and was performed with criteria developed a posteriori.
      CONCLUSION: Despite the limited number of recommendations for which agreement was
      found, guidelines did agree on careful antipsychotic use for BPSD. Adverse events
      might outweigh the supporting evidence of efficacy, weakening the recommendation.
      More pivotal trials on the effectiveness of non-pharmacological interventions, as
      well as guidelines specifically focusing on BPSD, are needed.

PMID- 21856453
TI  - Immune regulatory mechanisms in ANCA-associated vasculitides.
AB  - A group of primary vasculitides is associated with the presence of anti
      neutrophil cytoplasmic autoantibodies (ANCA). In these diseases, the contribution
      of ANCA to disease pathogenesis has been studied extensively. Also, in patients
      with ANCA-associated vasculitides, the T lymphocyte compartment is dysregulated,
      as aberrant distribution and function of T cell subsets has been shown. In this
      review we will discuss the putative role of T lymphocytes in inflammation and
      granuloma formation, as well as the involvement of B cell compartments in the
      pathophysiology of ANCA-associated vasculitis.

PMID- 21856454
TI  - Lung meridian acupuncture point skin impedance in asthma and description of a
      mathematical relationship with FEV1.
AB  - Alteration in acupoint skin impedance is purportedly associated with health
      impairment. This study examined lung meridian acupoint skin impedance in healthy
      individuals and patients with controlled asthma and the relationship if any with
      Forced Expiratory Volume in 1s (FEV(1)). Twenty-eight subjects diagnosed with
      asthma and 28 age and gender-matched healthy subjects had their FEV(1) and skin
      impedance, at acupoints LU 7 (Lieque) and LU 9 (Taiyuan) on the lung meridian,
      measured. Skin impedance was significantly higher in subjects with asthma
      (p<0.05) and negatively correlated with percent predicted FEV(1) (r=-0.34 to 
      0.40, p<0.005). The Receiver Operating Characteristic (ROC) suggested the cutoff
      point for logarithm-transformed mean of skin impedance for asthma was >=3.59 unit
      (sensitivity=82.1%, specificity=82.1%) (AUC=0.878, p<0.001). A regression
      prediction equation of asthma was derived. This study suggests that acupoint skin
      impedance on the lung meridian may reflect the asthma condition. The use of skin
      impedance as an adjunctive, objective assessment in asthma screening and
      treatment monitoring, warrants further investigation.

PMID- 21856455
TI  - Chaperonins induce an amyloid-like transformation of ovine prion protein: the
      fundamental difference in action between eukaryotic TRiC and bacterial GroEL.
AB  - Molecular chaperones have been shown to be involved in the processes taking place
      during the pathogenesis of various amyloid neurodegenerative diseases. However,
      contradictory literature reports suggest that different molecular chaperones can
      either stimulate or prevent the formation of amyloid structures from distinct
      amyloidogenic proteins. In the present work, we concentrated on the effects
      caused by two molecular chaperonins, ovine TRiC and bacterial GroEL, on the
      aggregation and conformational state of ovine PrP. Both chaperonins were shown to
      bind native PrP and to produce amyloid-like forms of ovine PrP enriched with beta
      structures but, while GroEL acted in an ATP-dependent manner, TRiC was shown to
      cause the same effect only in the absence of Mg-ATP (i.e. in the inactive form).
      In the presence of chaperonin GroEL, ovine PrP was shown to form micellar
      particles, approximately 100-200nm in diameter, which were observed both by
      dynamic light scattering assay and by electron microscopy. The content of these
      particles was significantly higher in the presence of Mg-ATP and, only under
      these conditions, GroEL produced amyloid-like species enriched with beta
      structures. TRiC was shown to induce the formation of amyloid fibrils observed by
      electron microscopy, but only in the absence of Mg-ATP. This study suggests the
      important role of the cytosolic chaperonin TRiC in the propagation of amyloid
      structures in vivo during the development of amyloid diseases and the possible
      role of the bacterial chaperonin GroEL, located in the intestinal microflora, in
      the induction of these diseases.

PMID- 21856456
TI  - Dicalcium phosphate cements: brushite and monetite.
AB  - Dicalcium phosphate cements were developed two decades ago and ever since there
      has been a substantial growth in research into improving their properties in
      order to satisfy the requirements needed for several clinical applications. The
      present paper presents an overview of the rapidly expanding research field of the
      two main dicalcium phosphate bioceramics: brushite and monetite. This review
      begins with a summary of all the different formulae developed to prepare
      dicalcium phosphate cements, and their setting reaction, in order to set the
      scene for the key cement physical and chemical properties, such as compressive
      and tensile strength, cohesion, injectability and shelf-life. We address the
      issue of brushite conversion into either monetite or apatite. Moreover, we
      discuss the in vivo behavior of the cements, including their ability to promote
      bone formation, biodegradation and potential clinical applications in drug
      delivery, orthopedics, craniofacial surgery, cancer therapy and biosensors.

PMID- 21856457
TI  - Oxidative stress induced carbonylation in human plasma.
AB  - The focus of this study was on the assessment of technology that might be of
      clinical utility in identification, quantification, characterization of
      carbonylation in human plasma proteins. Carbonylation is widely associated with
      oxidative stress diseases. Breast cancer patient samples were chosen as a stress
      positive case based on the fact that oxidative stress has been reported to be
      elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that
      breast cancer patients in this study were indeed experiencing significant
      oxidative stress. Carbonyl groups in proteins from freshly drawn blood were
      derivatized with biotin hydrazide after which the samples were dialyzed and the
      biotinylated proteins subsequently selected, digested and labeled with iTRAQTM
      heavy isotope coding reagent(s). Four hundred sixty proteins were identified and
      quantified, 95 of which changed 1.5 fold or more in concentration. Beyond
      confirming the utility of the analytical method, association of protein
      carbonylation was examined as well. Nearly one fourth of the selected proteins
      were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by
      unbiased knowledge assembly methods indicated the most likely disease associated
      with the proteins was breast neoplasm. Pathway analysis showed the proteins which
      changed in carbonylation were strongly associated with Brca1, the breast cancer
      type-1 susceptibility protein. Pathway analysis indicated the major molecular
      functions of these proteins are defense, immunity and nucleic acid binding.

PMID- 21856459
TI  - Regulatory perspective on translating proteomic biomarkers to clinical
      diagnostics.
AB  - Issues associated with the translation of complex proteomic biomarkers from
      discovery to clinical diagnostics have been widely discussed among academic
      researchers, government agencies, as well as assay and instrumentation
      manufacturers. Here, we provide an overview of the regulatory framework and type
      of information that is typically required in order to evaluate in vitro
      diagnostic tests regulated by the Office of In Vitro Diagnostic Device Evaluation
      and Safety (OIVD) at the US Food and Drug Administration (FDA), with the focus on
      some of the issues specific to protein-based complex tests. Technological points
      pertaining to mass spectrometry platforms and assessment of potential concerns
      important for assurance of safety and effectiveness of this type of assays when
      introduced into clinical diagnostic use, as well as general approaches for
      evaluating the performance of these devices, are discussed.

PMID- 21856458
TI  - A multidisciplinary study on the effects of phloem-limited viruses on the
      agronomical performance and berry quality of Vitis vinifera cv. Nebbiolo.
AB  - Viral infections are known to have a detrimental effect on grapevine yield and
      performance, but there is still a lack of knowledge about their effect on the
      quality and safety of end products. Vines of Vitis vinifera cv. Nebbiolo clone
      308, affected simultaneously by Grapevine leafroll-associated virus 1 (GLRaV-1),
      Grapevine virus A (GVA), and Rupestris stem pitting associated virus (RSPaV),
      were subjected to integrated analyses of agronomical performance, grape berry
      characteristics, instrumental texture profile, and proteome profiling. The
      comparison of performance and grape quality of healthy and infected vines
      cultivated in a commercial vineyard revealed similar shoot fertility, number of
      clusters, total yield, with significant differences in titratable acidity, and
      resveratrol content. Also some texture parameters such as cohesiveness and
      resilience were altered in berries of infected plants. The proteomic analysis of
      skin and pulp visualized about 400 spots. The ANOVA analysis on 2D gels revealed
      significant differences among healthy and virus-infected grape berries for 12
      pulp spots and 7 skin spots. Virus infection mainly influenced proteins involved
      in the response to oxidative stress in the berry skin, and proteins involved in
      cell structure metabolism in the pulp.

PMID- 21856460
TI  - Nuclear proteome analysis reveals a role of Vav1 in modulating RNA processing
      during maturation of tumoral promyelocytes.
AB  - Vav1 is a key molecule in the ATRA-induced acquisition of a mature phenotype by
      tumoral myeloid precursors. Since ATRA acts throughout events that require
      extensive changes of nuclear architecture and activity and considering that Vav1
      accumulates inside the nuclear compartment of differentiating APL-derived cells,
      the possible role of this protein in modulating the nuclear proteome was
      investigated. Membrane-depleted nuclei purified from NB4 cells induced to
      differentiate with ATRA in the presence of forcedly down-modulated Vav1 were
      subjected to 2D-DIGE followed by mass spectra analysis. The obtained data
      demonstrated that, in NB4 cells treated with ATRA, Vav1 is involved in
      determining the nuclear amount of proteins involved in molecular complexes with
      DNA and may participate to RNA processing by carrying in the nucleus molecules
      involved in modulating mRNA production and stability, like hnRNPs and SR
      proteins. Our results provide the first evidence that, at least in maturation of
      tumoral myeloid precursors, Vav1 is part of interconnected networks of
      functionally related proteins ended to regulate different aspects of gene
      expression. Since defects in mRNA processing are common in tumor development, our
      data suggest that Vav1 is a potential target molecule for developing new anti
      cancer strategies.

PMID- 21856461
TI  - Comparison of 2D and 3D bone microarchitecture evaluation at the femoral neck,
      among postmenopausal women with hip fracture or hip osteoarthritis.
AB  - OBJECTIVES: High resolution peripheral quantitative tomography (HR-pQCT) is used
      more widely to assess microarchitecture, but we are lacking comparisons between
      HR-pQCT and histomorphometry, which is considered the gold standard. They have
      only been assessed on different anatomical regions. The purpose of our study was
      to assess the microarchitecture and the relative contribution of cortical and
      trabecular bone in hip fracture with this 3D imaging technique, compared with the
      2D histomorphometry. MATERIAL AND METHODS: We compared the distribution of
      cortical and trabecular bone in the ultradistal femoral neck samples (~3mm thick)
      obtained after total hip replacement in 21 hip osteoarthritis (HOA, 66+/-8yrs)
      and 20 hip fracture (HF, 79+/-8yrs) menopausal women by a direct 3D evaluation
      method (HR-pQCT: XtremeCT, Scanco Medical AG) and by histomorphometry, performed
      and averaged on three 10MUm-thick sections 800MUm apart. RESULTS: Significant
      correlations were found between both techniques for trabecular bone volume,
      number, thickness, separation and cortical thickness (0.51<r'<0.81, p<0.01). The
      connectivity was also significantly correlated (r'=0.58, p<0.001) between both
      techniques, as well as the trabecular bone pattern factor measured in 2D with the
      structural model index (SMI) measured in 3D (r'=0.62, p<0.001). However HR-pQCT
      overestimated the absolute value of most parameters, with higher values being
      even more overestimated. The agreement between the two techniques was weak for
      cortical porosity. With the 3D measurements we found that trabecular bone volume
      was 43% lower in HF than HOA (p<0.01), associated with loss of trabecular
      connectivity (-50%, p<0.01) and a more rod-like structure (SMI, 22%, p<0.01),
      mainly at the inferior (34%, p<0.01) and posterior (22%, p<0.05) quadrants.
      Cortical thickness was found to be lower in the posterior quadrants (-22%,
      p<0.05) and tended to be lower in HF than in HOA at the inferior quadrant (-14%,
      p=0.08), but it was still the highest at the inferior quadrant in both groups. In
      conclusion, 3D methods confirmed the alteration of trabecular and cortical bone
      found by histomorphometry in HF compared with HOA and the frequency of the rod
      like structure in HF.

PMID- 21856462
TI  - On the horizon in heart failure.

PMID- 21856463
TI  - Doctors striking in Israel.

PMID- 21856464
TI  - South Africa should step up oversight of maternal care.

PMID- 21856465
TI  - Cardiac myosin activation: will theory and practice coincide?

PMID- 21856466
TI  - Predictive ability of coronary artery calcium and CRP.

PMID- 21856467
TI  - Antithrombin alternatives in STEMI.

PMID- 21856469
TI  - John Teerlink: Renaissance man and leader in heart failure research.

PMID- 21856470
TI  - Radial versus femoral access in acute coronary syndromes.

PMID- 21856471
TI  - Radial versus femoral access in acute coronary syndromes.

PMID- 21856474
TI  - Promise of extended-release naltrexone is a red herring.

PMID- 21856473
TI  - New antithrombotic drugs and European approval processes.

PMID- 21856476
TI  - Injectable extended-release naltrexone for opioid dependence.

PMID- 21856477
TI  - Injectable extended-release naltrexone for opioid dependence.

PMID- 21856478
TI  - Injectable extended-release naltrexone for opioid dependence.

PMID- 21856480
TI  - Dose-dependent augmentation of cardiac systolic function with the selective
      cardiac myosin activator, omecamtiv mecarbil: a first-in-man study.
AB  - BACKGROUND: Decreased systolic function is central to the pathogenesis of heart
      failure in millions of patients worldwide, but mechanism-related adverse effects
      restrict existing inotropic treatments. This study tested the hypothesis that
      omecamtiv mecarbil, a selective cardiac myosin activator, will augment cardiac
      function in human beings. METHODS: In this dose-escalating, crossover study, 34
      healthy men received a 6-h double-blind intravenous infusion of omecamtiv
      mecarbil or placebo once a week for 4 weeks. Each sequence consisted of three
      ascending omecamtiv mecarbil doses (ranging from 0.005 to 1.0 mg/kg per h) with a
      placebo infusion randomised into the sequence. Vital signs, blood samples,
      electrocardiographs (ECGs), and echocardiograms were obtained before, during, and
      after each infusion. The primary aim was to establish maximum tolerated dose (the
      highest infusion rate tolerated by at least eight participants) and plasma
      concentrations of omecamtiv mecarbil; secondary aims were evaluation of
      pharmacodynamic and pharmacokinetic characteristics, safety, and tolerability.
      This study is registered at ClinicalTrials.gov, number NCT01380223. FINDINGS: The
      maximum tolerated dose of omecamtiv mecarbil was 0.5 mg/kg per h. Omecamtiv
      mecarbil infusion resulted in dose-related and concentration-related increases in
      systolic ejection time (mean increase from baseline at maximum tolerated dose, 85
      [SD 5] ms), the most sensitive indicator of drug effect (r(2)=0.99 by dose),
      associated with increases in stroke volume (15 [2] mL), fractional shortening (8%
      [1]), and ejection fraction (7% [1]; all p<0.0001). Omecamtiv mecarbil increased
      atrial contractile function, and there were no clinically relevant changes in
      diastolic function. There were no clinically significant dose-related adverse
      effects on vital signs, serum chemistries, ECGs, or adverse events up to a dose
      of 0.625 mg/kg per h. The dose-limiting toxic effect was myocardial ischaemia due
      to excessive prolongation of systolic ejection time. INTERPRETATION: These first
      in-man data show highly dose-dependent augmentation of left ventricular systolic
      function in response to omecamtiv mecarbil and support potential clinical use of
      the drug in patients with heart failure. FUNDING: Cytokinetics Inc.

PMID- 21856481
TI  - The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac
      function in systolic heart failure: a double-blind, placebo-controlled,
      crossover, dose-ranging phase 2 trial.
AB  - BACKGROUND: Many patients with heart failure remain symptomatic and have a poor
      prognosis despite existing treatments. Decreases in myocardial contractility and
      shortening of ventricular systole are characteristic of systolic heart failure
      and might be improved by a new therapeutic class, cardiac myosin activators. We
      report the first study of the cardiac myosin activator, omecamtiv mecarbil, in
      patients with systolic heart failure. METHODS: We undertook a double-blind,
      placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the
      effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2,
      24, or 72 h to patients with stable heart failure and left ventricular systolic
      dysfunction receiving guideline-indicated treatment. Clinical assessment
      (including vital signs, echocardiograms, and electrocardiographs) and testing of
      plasma drug concentrations took place during and after completion of each
      infusion. The primary aim was to assess safety and tolerability of omecamtiv
      mecarbil. This study is registered at ClinicalTrials.gov, NCT00624442. FINDINGS:
      45 patients received 151 infusions of active drug or placebo. Placebo-corrected,
      concentration-dependent increases in left ventricular ejection time (up to an 80
      ms increase from baseline) and stroke volume (up to 9.7 mL) were recorded,
      associated with a small reduction in heart rate (up to 2.7 beats per min;
      p<0.0001 for all three measures). Higher plasma concentrations were also
      associated with reductions in end-systolic (decrease of 15 mL at >500 ng/mL,
      p=0.0026) and end-diastolic volumes (16 mL, p=0.0096) that might have been more
      pronounced with increased duration of infusion. Cardiac ischaemia emerged at high
      plasma concentrations (two patients, plasma concentrations roughly 1750 ng/mL and
      1350 ng/mL). For patients tolerant of all study drug infusions, no consistent
      pattern of adverse events with either dose or duration emerged. INTERPRETATION:
      Omecamtiv mecarbil improved cardiac function in patients with heart failure
      caused by left ventricular dysfunction and could be the first in class of a new
      therapeutic agent. FUNDING: Cytokinetics Inc.

PMID- 21856482
TI  - Associations between C-reactive protein, coronary artery calcium, and
      cardiovascular events: implications for the JUPITER population from MESA, a
      population-based cohort study.
AB  - BACKGROUND: The JUPITER trial showed that some patients with LDL-cholesterol
      concentrations less than 3.37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive
      protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with
      rosuvastatin, although absolute rates of cardiovascular events were low. In a
      population eligible for JUPITER, we established whether coronary artery calcium
      (CAC) might further stratify risk; additionally we compared hsCRP with CAC for
      risk prediction across the range of low and high hsCRP values. METHODS: 950
      participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all
      criteria for JUPITER entry. We compared coronary heart disease and cardiovascular
      disease event rates and multivariable-adjusted hazard ratios after stratifying by
      burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed
      to treat (NNT) by applying the benefit recorded in JUPITER to the event rates
      within each CAC strata. FINDINGS: Median follow-up was 5.8 years (IQR 5.7-5.9).
      444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in
      this group, rates of coronary heart disease events were 0.8 per 1000 person
      years. 74% of all coronary events were in the 239 (25%) of participants with CAC
      scores of more than 100 (20.2 per 1000 person-years). For coronary heart disease,
      the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for
      scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19.
      In the total study population, presence of CAC was associated with a hazard ratio
      of 4.29 (95% CI 1.99-9.25) for coronary heart disease, and of 2.57 (1.48-4.48)
      for cardiovascular disease. hsCRP was not associated with either disease after
      multivariable adjustment. INTERPRETATION: CAC seems to further stratify risk in
      patients eligible for JUPITER, and could be used to target subgroups of patients
      who are expected to derive the most, and the least, absolute benefit from statin
      treatment. Focusing of treatment on the subset of individuals with measurable
      atherosclerosis could allow for more appropriate allocation of resources.
      FUNDING: National Institutes of Health-National Heart, Lung, and Blood Institute.

PMID- 21856485
TI  - Medical therapy for chronic heart failure.
AB  - Understanding of contemporary pharmacological therapy for chronic heart failure
      continues to evolve. In this Review, we discuss how findings from clinical trials
      have caused the roles of old therapies to be expanded and past treatment
      algorithms to be challenged. Several trials investigating preserved ejection
      fraction as a measure of heart failure had disappointing results, although
      important studies are in progress. Many novel therapeutic approaches for heart
      failure have emerged and are discussed in this review. The pharmacological
      treatments for heart failure continue to change, with many exciting possibilities
      for the future.

PMID- 21856483
TI  - Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary
      intervention for ST-elevation myocardial infarction: the international randomised
      open-label ATOLL trial.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction has traditionally been supported by unfractionated heparin,
      which has never been directly compared with a new anticoagulant using consistent
      anticoagulation and similar antiplatelet strategies in both groups. We compared
      traditional heparin treatment with intravenous enoxaparin in primary PCI.
      METHODS: In a randomised open-label trial, patients presenting with ST-elevation
      myocardial infarction were randomly assigned (1:1) to receive an intravenous
      bolus of 0.5 mg/kg of enoxaparin or unfractionated heparin before primary PCI.
      Wherever possible, medical teams travelling in mobile intensive care units
      (ambulances) selected, randomly assigned (using an interactive voice response
      system at the central randomisation centre), and treated patients. Patients who
      had received any anticoagulant before randomisation were excluded. Patients and
      caregivers were not masked to treatment allocation. The primary endpoint was 30
      day incidence of death, complication of myocardial infarction, procedure failure,
      or major bleeding. The main secondary endpoint was the composite of death,
      recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by
      intention to treat. This trial is registered at ClinicalTrials.gov, number
      NCT00718471. FINDINGS: 910 patients were assigned to treatment with enoxaparin
      (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126
      (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on
      unfractionated heparin (relative risk [RR] 0.83, 95% CI 0.68-1.01, p=0.06). The
      incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0.08),
      complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0.21), procedure
      failure (100 [26%] vs 109 [28%]; p=0.61), and major bleeding (20 [5%] vs 22 [5%];
      p=0.79) did not differ between groups. Enoxaparin resulted in a significantly
      reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR
      0.59, 95% CI 0.38-0.91, p=0.015). Death, complication of myocardial infarction,
      or major bleeding (46 [10%] vs 69 [15%] patients; p=0.03), death or complication
      of myocardial infarction (35 [8%] vs 57 [12%]; p=0.02), and death, recurrent
      myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0.04)
      were all reduced with enoxaparin. INTERPRETATION: Intravenous enoxaparin compared
      with unfractionated heparin significantly reduced clinical ischaemic outcomes
      without differences in bleeding and procedural success. Therefore, enoxaparin
      provided an improvement in net clinical benefit in patients undergoing primary
      PCI. FUNDING: Direction de la Recherche Clinique, Assistance Publique-Hopitaux de
      Paris; Sanofi-Aventis.

PMID- 21856486
TI  - Implantable cardioverter defibrillators and cardiac resynchronisation therapy.
AB  - Implantable cardioverter defibrillators and cardiac resynchronisation therapy
      (CRT) have become standard of care in modern treatment for heart failure. Results
      from trials have provided ample evidence that CRT, in addition to its proven
      benefits in patients with symptomatic heart failure (New York Heart Association
      [NYHA] class III), might also reduce morbidity and mortality in those with mildly
      symptomatic heart failure (NYHA class II). As a result, the 2010 European Society
      of Cardiology guidelines now recommend CRT for both patient populations. In this
      review we summarise and critically assess the landmark randomised clinical trials
      REVERSE, MADIT-CRT, and RAFT. Furthermore, we discuss the rationale and available
      evidence for other emerging indications of CRT, including its use in patients
      with a mildly reduced left ventricular ejection fraction (>35%), in those with a
      narrow QRS complex (<=120 ms), and in those with concomitant bradyarrhythmic
      pacemaker indications. We also focus on patients who do not respond to CRT, and
      on CRT optimisation.

PMID- 21856484
TI  - In search of new therapeutic targets and strategies for heart failure: recent
      advances in basic science.
AB  - Chronic heart failure continues to impose a substantial health-care burden,
      despite recent treatment advances. The key pathophysiological process that
      ultimately leads to chronic heart failure is cardiac remodelling in response to
      chronic disease stresses. Here, we review recent advances in our understanding of
      molecular and cellular mechanisms that play a part in the complex remodelling
      process, with a focus on key molecules and pathways that might be suitable
      targets for therapeutic manipulation. Such pathways include those that regulate
      cardiac myocyte hypertrophy, calcium homoeostasis, energetics, and cell survival,
      and processes that take place outside the cardiac myocyte--eg, in the myocardial
      vasculature and extracellular matrix. We also discuss major gaps in our current
      understanding, take a critical look at conventional approaches to target
      discovery that have been used to date, and consider new investigational avenues
      that might accelerate clinically relevant discovery.

PMID- 21856487
TI  - Telemedicine and remote management of patients with heart failure.
AB  - Advances in telecommunication technologies have created new opportunities to
      provide telemedical care as an adjunct to medical management of patients with
      heart failure. Meta-analyses suggest that telemedicine can reduce morbidity and
      mortality in such patients; however, two prospective clinical trials not included
      in the analyses do not support these findings. Therefore, the effectiveness of
      telemedicine in heart failure is not established. Telemedicine approaches range
      from computer-based support systems to programmes led by nurses and physicians.
      Standardisation and appropriate classification of telemedical systems are needed
      to enable accurate interpretation of clinical trials. Here we propose a
      classification of four generations of telemedicine in heart failure. Not all
      approaches are the same and not every patient with heart failure will need
      telemedicine. Crisis prevention and treatment, and stabilisation and self
      empowerment of patients are focuses of telemedicine in heart failure. The profile
      of patients who can potentially benefit from telemedicine is unknown and should
      be investigated in adequately powered randomised clinical trials. We are
      optimistic that telemedicine is an efficient approach and will become an
      important feature of management in heart failure.

PMID- 21856488
TI  - Coagulation: cascade!

PMID- 21856489
TI  - A cause with solutions: an American hemodialysis story.

PMID- 21856490
TI  - Quiz page September 2011: A patient with postpartum hypertension and seizure.

PMID- 21856491
TI  - Trial quality in nephrology: how are we measuring up?

PMID- 21856492
TI  - The role of implantable cardioverter-defibrillators in long-term dialysis
      patients.

PMID- 21856493
TI  - Regarding early initiation of dialysis.

PMID- 21856494
TI  - Sulfamethoxazole crystalluria.

PMID- 21856496
TI  - Do the benefits of peritoneal dialysis for polycystic kidney disease wane with
      time?

PMID- 21856497
TI  - Peritoneal dialysis for patients with polycystic kidney disease in Spain.

PMID- 21856499
TI  - Protection of repaired patellar tendons a surgical technique.
AB  - Patellar tendon avulsion repairs are a frequent necessity in knee arthroplasty
      and revisions. These repairs are often accompanied by compromised healing from
      previous surgeries, resulting in devitalization of tissues and vascular support
      with scar tissue formation. This study describes the use of a dynamic and
      flexible leash to limit excursion of the patella while protecting the fragile
      repair.

PMID- 21856500
TI  - Computer-assisted navigation of total knee arthroplasty for osteoarthritis in a
      patient with severe posttraumatic femoral deformity.
AB  - In the setting of extraarticular deformities of the knee, total knee arthroplasty
      (TKA) is difficult, as anatomical abnormalities obstruct identification of
      alignment landmarks and may preclude the use of traditional instrumentation. The
      long-term clinical value of computer assistance for TKA is a point of ongoing
      controversy. Few reports describe the use of computer-assisted orthopedic surgery
      as a method to decrease alignment outliers in TKA with associated posttraumatic
      deformities. In this report, a 70-year-old woman who had a severe distal femoral
      deformity from a previous open fracture underwent computer-assisted TKA for
      osteoarthritis. The use of a computer-assisted navigation system achieved a high
      degree of accuracy relative to the desired target alignment and led to improved
      function in a patient in which standard instrumentation was not feasible.

PMID- 21856503
TI  - Requirements for utilizing health care-based data sources for research.

PMID- 21856504
TI  - Minimally invasive treatment of metastatic pheochromocytoma and paraganglioma:
      efficacy and safety of radiofrequency ablation and cryoablation therapy.
AB  - PURPOSE: To evaluate the safety and efficacy of percutaneous ablation methods for
      the treatment of metastatic pheochromocytomas (PCCs) and paragangliomas (PGLs).
      MATERIALS AND METHODS: From May 2001 to November 2009, 10 patients (mean age 45
      years) with metastatic PCCs and PGLs were identified and treated with
      percutaneous ablation. All patients were given appropriate medication before the
      ablation procedure. Vital signs were monitored before, during, and after the
      procedure. There were 47 tumor ablations performed using radiofrequency (RF)
      ablation, cryoablation, or ethanol injection as determined by tumor location.
      RESULTS: In all patients, all metastatic lesions amendable to percutaneous
      ablation were treated; for 2 of 10 patients, all known metastases were treated.
      Successful ablation without evidence of recurrence was achieved in 56% (15 of 27)
      of primarily treated lesions in patients with available follow-up imaging. The
      time to disease progression after ablation was 7.2 months +/- 4.0. Amelioration
      of breakthrough hypertensive symptoms or metastasis-related pain was achieved in
      two of two patients and four of four patients, respectively, at clinical follow
      up. Comparison of intra-arterial blood pressure before, during, and after the
      procedures showed statistically significant differences in these median blood
      pressures (P = .004-.05). Major complications occurred after 2 of 18 (11%)
      ablation sessions, including one unplanned increase in level of patient care and
      one periprocedural death from complications related to bowel perforation.
      CONCLUSIONS: Local control of metastatic PCCs and PGLs with percutaneous ablation
      can play an important role in disease management when the lesions are
      unresectable surgically, and there is potential for prolongation of patient
      function or amelioration of metastasis-related symptoms.

PMID- 21856505
TI  - Percutaneous onyx embolization of cervical paragangliomas.
AB  - Cervical paragangliomas are a group of vascular neoplasms arising from the
      extraadrenal neuroendocrine system. The present report describes a series of six
      cases of cervical paragangliomas successfully and safely embolized preoperatively
      by means of ethylene vinyl alcohol copolymer delivered by percutaneous needle
      punctures without the need for balloon protection. Although the results are
      promising, further studies are needed to confirm the superiority of this method
      versus other embolization techniques and embolic agents.

PMID- 21856506
TI  - Outcomes of an algorithmic approach to management of pneumothorax complicating
      thermal ablation of pulmonary neoplasms.
AB  - PURPOSE: To investigate the outcomes of an algorithm for treatment of
      pneumothorax in association with radiofrequency (RF) and microwave (MW) ablation
      of pulmonary neoplasms. MATERIALS AND METHODS: This retrospective study included
      data from 248 ablation sessions for lung tumors in 164 patients (92 men; mean
      age, 59.7 y +/- 9.8): 200 RF ablations (80.6%) and 48 MW ablations (19.4%).
      Pneumothorax was classified as mild, moderate, or severe. Twelve patients
      developed mild pneumothorax and were observed for further complications, and 33
      developed moderate or severe pneumothorax and were managed with percutaneous
      aspiration of the pneumothorax. The decision to abort or continue ablation was
      determined based on clinical response to percutaneous aspiration, clinical
      distress, and feasibility of applying the applicator within the lesion. RESULTS:
      Incidence of pneumothorax was 18.1% (45 of 248 sessions), with four (8.9%)
      occurrences during MW ablation and 41 (91.1%) during RF ablation. Pneumothoraces
      were mild in 12 sessions (26.7%), moderate in 27 (60%), and severe in six
      (13.3%). Complete evacuation of the pneumothorax was achieved in 25 of 33
      sessions (75.8%). Intercostal tube drainage was indicated in eight sessions
      (24.2%), including six severe and two moderate pneumothoraces. Pneumothorax
      evolved immediately after thoracic puncture in 10 patients. Ablation therapy was
      aborted in two sessions in which severe pneumothorax occurred, and an intercostal
      chest tube was inserted. CONCLUSIONS: Mild pneumothorax can be managed by close
      observation without interruption of ablation therapy. Manual evacuation was an
      effective strategy for management of moderate pneumothorax and allowed for
      adequate positioning of the electrode, but did not suffice for severe and
      progressive pneumothorax, which required placement of an intercostal chest tube.

PMID- 21856507
TI  - Intraluminal diffuse large B-cell lymphoma within the left brachiocephalic vein.

PMID- 21856508
TI  - Successful balloon-occluded retrograde transvenous obliteration for large gastric
      varices in combination with temporary occlusion of the splenic artery.

PMID- 21856509
TI  - Percutaneous extraction of right atrial mass using the Angiovac aspiration
      system.

PMID- 21856510
TI  - Testicular artery embolization for the treatment of iatrogenic hemorrhage: report
      of two cases.

PMID- 21856511
TI  - Irvin Franklin "Dick" Hawkins, MD.

PMID- 21856512
TI  - The wrong place at the wrong time: geographic disparities in young people's HIV
      Risk.

PMID- 21856513
TI  - Toward a conceptual model linking community violence exposure to HIV-related risk
      behaviors among adolescents: directions for research.
AB  - PURPOSE: To present a conceptual framework which accounts for the relationship
      between community violence exposures (CVEs) and youth HIV risk behaviors.
      METHODS: This article provides an overview of existing research on the links
      between CVE and HIV risk for youth and offers a conceptual framework for
      clarifying how CVE might contribute to HIV sexual risk behaviors. RESULTS:
      Increasing empirical findings substantiate that the links between CVE and HIV
      risk behaviors among youth are mediated by psychological problem behaviors, low
      school success rates, and negative peer influences. CONCLUSIONS: Researchers have
      identified the behaviors that place teens at risk for becoming infected with HIV.
      However, most scholars have overlooked the potential importance of CVE in
      influencing such behaviors. This article presents new directions for adolescent
      research and HIV interventions on the basis of an integrated conceptual
      framework.

PMID- 21856514
TI  - A tale of two countries: rethinking sexual risk for HIV among young people in
      South Africa and the United States.
AB  - PURPOSE: To compare the sexual behaviors of young people in South Africa (SA) and
      the United States (US) with the aim to better understand the potential role of
      sexual behavior in HIV transmission in these two countries that have strikingly
      different HIV epidemics. METHODS: Nationally representative, population-based
      surveys of young people aged 18-24 years from SA (n = 7,548) and the US (n =
      13,451) were used for the present study. RESULTS: The prevalence of HIV was 10.2%
      in SA and <1% in the US. Young women and men in the US reported an earlier age of
      first sex than those in SA (mean age of coital debut for women: US [16.5], SA
      [17.4]; for men: US [16.4], SA [16.7]). The median number of lifetime partners is
      higher in the US than in SA: women: US (4), SA (2); men: US (4), SA (3). The use
      of condom at last sex is reported to be lower in the US than in SA: women: US
      (36.1%), SA (45.4%); men: US (48%), SA (58%). On average, young women in SA
      report greater age differences with their sex partners than young women in the
      US. CONCLUSION: Young people in the US report riskier sexual behaviors than young
      people in SA, despite the much higher prevalence of HIV infection in SA. Factors
      above and beyond sexual behavior likely play a key role in the ongoing
      transmission of HIV in South African youth, and thus should be urgently uncovered
      to develop maximally effective prevention strategies.

PMID- 21856517
TI  - Reduction of unnecessary intake of water and herbal teas on breast-fed infants: a
      randomized clinical trial with adolescent mothers and grandmothers.
AB  - PURPOSE: To evaluate the efficacy of counseling sessions on breast-feeding for
      adolescent mothers and maternal grandmothers on the reduction of unnecessary
      water and herbal teas intake on breast-fed infants. METHODS: A randomized
      clinical trial was conducted involving adolescent mothers, newborn infants, and
      maternal grandmothers allocated into four groups: mother and grandmother not
      cohabitating, without intervention; mother and grandmother not cohabitating, with
      intervention directed only toward mother; mother and grandmother cohabitating,
      without intervention; and mother and grandmother cohabitating, with intervention
      directed toward both. The intervention consisted of six counseling sessions on
      breastfeeding: in the maternity ward, and after birth on days 7, 15, 30, 60, and
      120 at home. The data about feeding practices were collected by telephone every
      month until the end of the sixth month of the baby's life. The effect of the
      intervention was measured by comparing the medians and the survival curves for
      initiation of water and/or tea intake in the first 6 months of life, and Cox
      regression was used to estimate its magnitude. RESULTS: The intervention had a
      positive effect for the group in which the adolescent mothers cohabitated with
      the baby's grandmother (hazard ratio = .53; 95% confidence interval = .35-.80),
      and also for the group in which they did not cohabitate with the baby's
      grandmother (hazard ratio = .48; 95% confidence interval = .31-.76). By comparing
      the medians of the time of initiation of water and/or tea intake between control
      and intervention groups, it was observed that the intervention postponed the use
      of these liquids in 67 days in the group in which mothers and grandmothers
      cohabitated and in 44 days in the group in which they did not live together.
      CONCLUSION: Multiple counseling sessions on infant feeding in the first 4 months
      postpartum for adolescent mothers and maternal grandmothers, when they
      cohabitate, proved to be an effective strategy to postpone the unnecessary water
      and/or tea intake of breast-fed infants.

PMID- 21856515
TI  - Using culturally sensitive media messages to reduce HIV-associated sexual
      behavior in high-risk African American adolescents: results from a randomized
      trial.
AB  - PURPOSE: To test the long-term effects of a mass media intervention that used
      culturally and developmentally appropriate messages to enhance human
      immunodeficiency virus (HIV)-preventive beliefs and behavior of high-risk African
      American adolescents. METHODS: Television and radio messages were delivered for
      more than 3 years in two cities (Syracuse, NY; and Macon, GA) that were randomly
      selected within each of the two regionally matched city pairs, with the other
      cities (Providence, RI; and Columbia, SC) serving as controls. African American
      adolescents, aged 14-17 years (N = 1,710), recruited in the four cities over a 16
      month period, completed audio computer-assisted self-interviews at recruitment
      and again at 3, 6, 12, and 18-months postrecruitment to assess the long-term
      effects of the media program. To identify the unique effects of the media
      intervention, youth who completed at least one follow-up and who did not test
      positive for any of the three sexually transmitted infections at recruitment or
      at 6-and 12-month follow-up were retained for analysis (N = 1,346). RESULTS: The
      media intervention reached virtually all the adolescents in the trial and
      produced a range of effects including improved normative condom-use negotiation
      expectancies and increased sex refusal self-efficacy. Most importantly, older
      adolescents (aged 16-17 years) exposed to the media program showed a less risky
      age trajectory of unprotected sex than those in the nonmedia cities. CONCLUSION:
      Culturally tailored mass media messages that are delivered consistently over time
      have the potential to reach a large audience of high-risk adolescents, to support
      changes in HIV-preventive beliefs, and to reduce HIV-associated risk behaviors
      among older youth.

PMID- 21856516
TI  - Patterns of chlamydia/gonorrhea positivity among voluntarily screened New York
      City public high school students.
AB  - PURPOSE: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are common
      sexually transmitted infections that disproportionately affect adolescents.
      Annual screening for CT for sexually active female adolescents is recommended. In
      2006, New York City began conducting CT/GC education, screening, and treatment in
      public high schools. We examine 3-year programmatic outcomes and the relationship
      between sexual activity, screening, and CT/GC positivity. METHODS: We describe
      the epidemiology of students who screened and those infected with CT/GC.
      Univariate, bivariate, and multivariate logistic regression analyses were
      performed to assess relationships between sex, race/ethnicity, age, sexual
      activity, and screening status; and the relationship between sexually transmitted
      infection positivity and sexual activity. RESULTS: Between July 2006 and June
      2009, we educated 57,418 students and screened 27,353 (47.6%) for CT/GC; 1,736
      (6.3%) students were reported to be infected with either organism. Students who
      screened positive were more likely to be females (8.9%), report black race (8.3%)
      and be >=16 years of age (6.6%-9.7%). Screening rates were 70.6% for students who
      were sexually active, 27.9% for those who had never had sex, and 47.3% for those
      who did not respond to the sexual activity question; CT/GC positivity was 7.2%,
      1.4%, and 6.1%, respectively. CONCLUSIONS: Black, older adolescent females were
      most likely to screen positive for CT/GC in this population. A large proportion
      of students who did not answer the sexual activity question chose to screen for
      CT/GC and screened positive. School screening programs should offer screening to
      all students regardless of reported sexual activity. Programs should target
      females and older adolescents.

PMID- 21856518
TI  - Psychometric testing of the breastfeeding self-efficacy scale-short form among
      adolescents.
AB  - PURPOSE: This study aimed to (a) psychometrically assess the Breastfeeding Self
      Efficacy Scale-Short Form (BSES-SF) antenatally and postnatally among
      adolescents, and (b) examine the relationship between breast-feeding self
      efficacy and adolescent demographic variables. The BSES-SF is used
      internationally but has not been psychometrically tested with an adolescent
      population. METHODS: A methodological study was conducted in which 103 pregnant
      adolescents were recruited from two prenatal clinics at a tertiary care setting
      in western Canada. The BSES-SF was administered at 34 weeks' gestation and again
      at 1 and 4 weeks postpartum. RESULTS: The Cronbach's alpha coefficient was .84
      for the antenatal assessment and .93 for the postnatal assessment. Antenatal BSES
      SF scores significantly predicted breast-feeding initiation, whereas antenatal
      and postnatal scores predicted duration and exclusivity to 4 weeks postpartum.
      Other reliability and validity results are consistent with previous research with
      adult samples. Study findings indicate prenatal classes and professional support
      may be particularly important sources of information to increase adolescent
      breast-feeding self-efficacy. CONCLUSIONS: Results provide evidence that the
      scale may be a valid and reliable measure of breast-feeding self-efficacy among
      adolescents, predicting breast-feeding initiation, duration, and exclusivity.

PMID- 21856519
TI  - Measurement of ethnic background in cross-national school surveys: agreement
      between students' and parents' responses.
AB  - PURPOSE: Indicators such as country of birth and language spoken at home have
      been used as proxy measures for ethnic background, but the validity of these
      indicators in surveys among school children remains unclear. This study aimed at
      comparing item response and student-parent agreement on four questions about
      country of birth and language spoken at home in three European countries.
      METHODS: We analyzed data from the Health Behaviour in School-aged Children
      (HBSC) Child-Parent Validation Study 2005, including 486 matched student-parent
      pairs from Denmark, Hungary, and Scotland. Selected items from the
      internationally standardized HBSC questionnaire were completed by 11-year-old
      students and their parents. We examined item response and student-parent
      agreement on the four HBSC Ethnic Background Indicators: the student's country of
      birth, mother's country of birth, father's country of birth, and language usually
      spoken at home. RESULTS: All item response rates were high for both students
      (>92%) and parents (>96%). The percent student-parent agreement was high on all
      four items (>97%). The strength of agreement ranged from good to excellent for
      all items indicated by the kappa value (between .60 and 1.00). Results were
      robust across countries. CONCLUSIONS: Our findings suggest that students as young
      as 11 years are able to provide valid responses to four simple questions about
      country of birth and language spoken at home. The four HBSC Ethnic Background
      Indicators can be useful in epidemiologic studies on identification of subgroups
      that may receive unequal prevention services or in assessment of how risk
      factors, symptoms, and diseases may differ by ethnic background among school
      children.

PMID- 21856520
TI  - Adverse adolescent relationship histories and young adult health: cumulative
      effects of loneliness, low parental support, relationship instability, intimate
      partner violence, and loss.
AB  - PURPOSE: To examine the associations between adverse interpersonal relationship
      histories experienced during adolescence and health in young adulthood in a
      large, nationally representative sample. METHODS: Using data from Waves I, II,
      and III of the National Longitudinal Study of Adolescent Health, multiple adverse
      relationship experiences were examined, including high loneliness, low perceived
      parental support, frequent transitions in romantic relationships (relationship
      instability), exposure to intimate partner violence, and loss by death of
      important relationship figures. These histories are assessed, both individually
      and in a relationship risk index, as predictors of self-reported general health
      and depressive symptoms at Wave III (ages, 18-27), controlling for baseline (Wave
      I) health and for demographic and health behavior covariates. RESULTS: Net of
      baseline health and covariates, each type of relationship risk (experienced
      between Wave I and Wave III) was related to either depression or general health
      at Wave III, with the strongest effects seen for exposure to intimate partner
      violence. In addition, a cumulative relationship risk index examining the extent
      to which youth experienced high levels of multiple relationship risk factors
      revealed that each additional adverse relationship experience increased the odds
      of reporting worse mental and general health at Wave III, with increases
      occurring in an additive manner. CONCLUSION: Multiple types of adverse
      relationship experiences predicted increases in poorer general health and
      depressive symptoms from adolescence to early adulthood. Consistent with a
      cumulative risk hypothesis, the more types of adverse relationship a youth
      experienced, the worse were their young adult health outcomes.

PMID- 21856521
TI  - Sexual abuse in childhood and adolescence and the risk of early pregnancy among
      women ages 18-22.
AB  - PURPOSE: This clinic- and community-based study of young women investigated the
      relationship between previous sexual abuse and early pregnancy, examining the
      effect of the developmental period in which sexual abuse occurred and type of
      sexual abuse, while also providing methodological advances in the assessment of
      distinctive sexual abuse and its sequelae. METHODS: Secondary data analysis using
      Cox proportional hazards models was conducted to determine the association
      between sexual abuse in childhood, in adolescence, or both, and risk of early
      pregnancy among 1,790 young women. In addition, this study examined the type of
      sexual abuse that occurred during each period. RESULTS: As compared with women
      with no history of sexual abuse, women who experienced sexual abuse only in
      childhood had a 20% greater hazard of pregnancy; women who experienced sexual
      abuse only in adolescence had a 30% greater hazard of pregnancy; and women who
      experienced sexual abuse in both childhood and adolescence had an 80% greater
      hazard of pregnancy. Across these periods, attempted rape and rape were
      associated with an increased hazard of pregnancy. The association between sexual
      abuse and pregnancy was mediated by age at first intercourse and moderated by a
      woman's education level. CONCLUSION: This study provides evidence that both the
      developmental timing and the type of sexual abuse contributes to an increased
      risk for early pregnancy. The study findings indicate that sexual abuse leads to
      an earlier age of first sexual intercourse, which in turn increases the
      likelihood of an early pregnancy. Women with higher educational attainment are
      less likely to experience early pregnancy as a result of abuse.

PMID- 21856522
TI  - Peer relational victimization and somatic complaints during adolescence.
AB  - PURPOSE: To develop effective prevention and intervention efforts that optimize
      adolescent health, factors must be identified that affect health outcomes. The
      purpose of this study was to examine the association between somatic
      symptomatology and experiences with relational victimization (RV). METHODS: We
      prospectively tested the unique role of relational peer victimization in
      predicting adolescents' somatic complaints (SC), while accounting for their
      previous physical symptoms and peer victimization experiences (i.e., relational
      and physical victimization), as well as concurrent experiences with physical
      victimization (PV). Questionnaires were administered to 1,595 students (52%
      females) from eight schools in one school district (grades, 5-8) in the
      Midwestern part of the United States during the fall and spring sessions of the
      academic school year. Self-reported measures included demographic
      characteristics, victimization experiences, and assessment of SC. RESULTS: RV was
      a unique predictor of increased somatic symptoms, even after controlling for
      adolescents' sex, grade level, initial SC, previous victimization experiences,
      and concurrent experiences with PV. Notably, RV was a stronger predictor of
      somatic symptoms than was PV. CONCLUSIONS: Our findings underscore the need for a
      comprehensive approach when addressing adolescents' physical health symptoms.
      Adolescents may benefit from clinicians looking beyond the obvious and using
      gentle probing to uncover how unique experiences with RV may be associated with
      overall health.

PMID- 21856523
TI  - Alterations in downstream mediators involved in central control of eating
      behavior in obese adolescents submitted to a multidisciplinary therapy.
AB  - OBJECTIVE: The aim of this study was to verify the effects of a multidisciplinary
      therapy (24 weeks) on neurohormonal control of food intake, specifically in
      orexigenic (total ghrelin, agouti-related protein [AgRP], neuropeptide Y [NPY],
      and melanin-concentrating hormone) and anorexigenic factors (leptin, insulin, and
      alpha-melanocyte stimulating hormone [alpha-MSH]), in obese adolescents. METHODS:
      A total of 88 adolescents (38 boys and 50 girls), including 62 obese and 26
      normal-weight, aged 15-19 years were recruited. Obese adolescents were submitted
      to a 24-week multidisciplinary therapy. AgRP, NPY, melanin-concentrating hormone,
      leptin, insulin, glucose, alpha-MSH, total ghrelin, and food intake were measured
      at three stages (at baseline, after 12 weeks, and after 24 weeks). RESULTS: At
      baseline, obese adolescents showed hyperleptinemia (circulating leptin levels,
      which were, in boys and girls, 40 and 35 times higher than in normal-weight
      subjects, respectively). After 24 weeks, these values decreased in all obese
      patients. Our results showed no differences in ghrelin levels between obese and
      normal-weight adolescents, in both genders. However, obese boys reduced their
      plasma ghrelin concentration after 24 weeks of therapy (p < .05). The
      multidisciplinary therapy decreased NPY and AgRP values and increased alpha-MSH;
      simultaneously with these changes there was a decrease in total food intake after
      24 weeks of therapy. CONCLUSIONS: We can conclude that the multidisciplinary
      therapy was efficient to modulate neurohormonal control of food intake in obese
      adolescents.

PMID- 21856524
TI  - Longitudinal and secular trends in parental encouragement for healthy eating,
      physical activity, and dieting throughout the adolescent years.
AB  - PURPOSE: Parental encouragement for healthy eating and physical activity has been
      found to be associated with the long-term healthy habits of adolescents, whereas
      parental encouragement to diet has been associated with disordered eating
      behaviors among adolescents. However, little is known about how parental
      encouragement changes as adolescents grow older (longitudinal trends), or how
      parental encouragement has changed over time (secular trends). This study
      examined 5-year longitudinal and secular trends in adolescents' report of their
      parents' encouragement to eat healthily, be physically active, and diet. METHODS:
      Project Eating Among Teens surveyed a cohort of Minnesota adolescents (n = 2,516)
      in the years 1999 and 2004. Mixed-model regressions were used to assess changes
      in adolescents' reports of parental encouragement from early to middle
      adolescence (middle school to high school) and from middle to late adolescence
      (high school to post-high school), and secular changes in parental encouragement
      among middle adolescents between the years 1999 and 2004. RESULTS:
      Longitudinally, there were significant decreases in parental encouragement to eat
      healthy food, be active, and diet between early and middle adolescence. Between
      middle and late adolescence, among males parental encouragement for all behaviors
      decreased, whereas among females parental encouragement to diet increased. Few
      secular changes in parental encouragement were observed between 1999 and 2004.
      CONCLUSION: Given the importance of parental support for healthy eating and
      physical activity, efforts should be made to help parents maintain a high level
      of encouragement for their children's healthy behavior throughout adolescence.
      Parents of late adolescent females should aim to decrease the pressure on their
      daughters to diet during these critical developmental years.

PMID- 21856526
TI  - A longitudinal analysis of predictors of male and female adolescents' transitions
      to intimate sexual behavior.
AB  - PURPOSE: Determining predictors of sexual transitions is essential for developing
      health interventions. METHODS: Adolescents (13-16 years) completed baseline and 6
      month surveys assessing psychosocial factors and sexual behavior. RESULTS AND
      CONCLUSIONS: Lower self-esteem for boys and higher lifetime alcohol use for girls
      predicted transitions to more intimate sex. These differential profiles may
      warrant tailored health initiatives.

PMID- 21856525
TI  - Risk and protective factors for adolescent substance use in washington state, the
      United States and Victoria, Australia: a longitudinal study.
AB  - PURPOSE: To compare the levels of risk and protective factors and the predictive
      influence of these factors on alcohol, tobacco, and cannabis use over a 12-month
      follow-up period in Washington State in the United States and in Victoria,
      Australia. METHOD: The study involved a longitudinal school-based survey of
      students drawn as a two-stage cluster sample recruited through schools, and
      administered in the years 2002 and 2003 in both states. The study used statewide
      representative samples of students in the seventh and ninth grades (n = 3,876) in
      Washington State and Victoria. RESULTS: Washington State students, relative to
      Victorian students, had higher rates of cannabis use but lower rates of alcohol
      and tobacco use at time 1. Levels of risk and protective factors showed few but
      important differences that contribute to the explanation of differences in
      substance use; Washington State students, relative to Victorian students,
      reported higher religiosity (odds ratio, .96 vs. .79) and availability of
      handguns (odds ratio, 1.23 vs. 1.18), but less favorable peer, community, and
      parental attitudes to substance use. The associations with substance use at
      follow-up are generally comparable, but in many instances were weaker in
      Washington State. CONCLUSIONS: Levels of risk and protective factors and their
      associations with substance use at follow-up were mostly similar in the two
      states. Further high-quality longitudinal studies to establish invariance in the
      relations between risk and protective factors and substance use in adolescence
      across diverse countries are warranted.

PMID- 21856527
TI  - Condom availability program in an inner city public school: effect on the rates
      of gonorrhea and chlamydia infection.
AB  - PURPOSE: Sexual activity and sexually transmitted infection (STI) rates are high
      in adolescents. In this study, we sought to determine whether the initiation of a
      school-based condom availability program was associated with a decrease in STI
      rates. METHODS: We compared the rates of STIs in 15-19-yr-olds reported to the
      Massachusetts Department of Public Health for the 3 years before and after a
      condom availability program was introduced in Holyoke, MA, as compared with a
      similar city, Springfield, MA, which did not have such a program. RESULTS:
      Holyoke males, aged 15-19 years, showed a 47% decrease in the rates of gonorrhea
      and chlamydia infection combined over the 3 years after the implementation of the
      condom availability program, whereas similar aged males in Springfield had a 23%
      increase in the rates of gonorrhea and chlamydia infection. The difference in
      regression slopes in this period was significant (p < .01). Females, aged 15-19
      years, from either Holyoke or Springfield, showed moderate, variable changes in
      rates of STIs after 2005; there was no significant difference in the regression
      slopes of STIs between Holyoke and Springfield. CONCLUSIONS: Initiating a condom
      availability program in a city's high school was associated with a decrease in
      STI rates for 15-19-yr-old males but not females.

PMID- 21856528
TI  - Adolescent mothers' sexual, contraceptive, and emotional relationship content
      with the fathers of their children following a first diagnosis of sexually
      transmitted infection.
AB  - PURPOSE: A sexually transmitted infection (STI) diagnosis may profoundly change
      the meaning of adolescent women's relationships, particularly when the
      relationship involves a shared child. This study explored the sexual,
      contraceptive, and emotional characteristics of sexual partners with whom
      adolescent women had and did not have children in the 3 months after the first
      STI diagnosis. METHODS: Adolescent women (n = 387; age: 14-17 years at
      enrollment) were tested quarterly for STI and completed partner-specific items on
      emotional and sexual relationship content. We used nonparametric statistics
      (SPSS/18.0) to compare these characteristics between partners with whom these
      adolescent women did (n = 20) or did not (n = 118) share a child. RESULTS: Rates
      of condom use at last sex, overall condom use, and condom insistence were lower
      with sexual partners involving shared children as compared with childless sexual
      partners. Relationship status, commitment to partner, and using no method of
      contraception were more common in parous sexual relationships as compared with
      nulliparous sexual relationships after an STI. CONCLUSIONS: After an STI,
      adolescent women have different sexual risk behaviors with the fathers of their
      children, even after a signal event such as a recent STI diagnosis. Tailored
      counseling may specifically address the challenges of STI prevention with
      partners who have the unique status of being the "father of the baby."

PMID- 21856529
TI  - Is waist circumference a better predictor of insulin resistance than body mass
      index in U.S. adolescents?
AB  - PURPOSE: To determine whether waist circumference (WC) is a better predictor of
      insulin resistance (IR) than body mass index (BMI) in U.S. adolescents aged 12-18
      years. METHODS: Using data from the National Health and Nutrition Examination
      Survey 1999-2002, we evaluated an ethnically diverse sample of 1,571 adolescents
      with regard to BMI, WC, and fasting glucose and insulin levels. Children were
      classified as having IR if they had a homeostasis model assessment of insulin
      resistance (insulin [U/mL] * glucose [mmol/L]/22.5) of greater than 4.39.We
      created receiver operating characteristic curves predicting IR across various
      thresholds of WC and BMI, and area under the curve was compared. RESULTS: The
      prevalence rate of IR in the study population was 11.8%. Measures of test
      performance (sensitivity and specificity) for predicting IR were similar for
      abnormal BMI and WC thresholds; that is, thresholds of BMI 85th% and WC 75th% and
      thresholds of BMI 95th% and WC 90th% were quite similar. There were no
      significant differences in area under the curve for WC versus BMI (.85; 95% CI,
      .83-.88; p = .84) either for the overall population or for specific racial
      groups. CONCLUSIONS: WC does not seem to provide a distinct advantage over BMI
      for identifying adolescents with IR.

PMID- 21856530
TI  - Hearing loss among low-SES adolescent girls.

PMID- 21856532
TI  - Scars: clinical evidence base and patient impact.

PMID- 21856533
TI  - Skin: histology and physiology of wound healing.
AB  - It is important to understand the histology and physiology of skin for the
      prediction and optimization of wound healing. Optimal postoperative wound healing
      to minimize scarring entails minimizing local, systemic, and environmental
      factors that lead to poor wound healing. Keeping the wound clean and moist,
      minimizing trauma, and infection are the local wound tenets. Systemic tenets
      include minimizing medications that inhibit processes of wound healing,
      maintaining adequate nutrition, pain palliation, UV protection, and smoking
      cessation. This article presents the dynamic process of wound healing and the
      basic tenets to minimize scarring.

PMID- 21856534
TI  - Scar revision techniques: z-plasty, w-plasty, and geometric broken line closure.
AB  - This article addresses the use of scar revision surgery as it relates to the use
      of Z-plasty, W-plasty, and geometric broken line closure. Each of these
      techniques is discussed in detail and the author provides perspectives regarding
      the indications, advantages, and limitations of each procedure. The surgeon
      should be experienced with each of these and apply these methods as appropriate.
      As with any technique, careful preoperative planning along with meticulous
      execution will lead to optimal results.

PMID- 21856535
TI  - Elegant solutions for complex paramedian forehead flap reconstruction.
AB  - Nasal reconstruction is one of the most challenging aspects of facial plastic
      surgery. The authors present reconstructive techniques to maximize the final
      aesthetic result and minimize scarring. They discuss techniques used in nasal
      reconstruction with a paramedian forehead flap (PMFF) that help to achieve these
      goals and minimize the chance of complications, including performing a surgical
      delay, using generous, supportive cartilage grafts, adding extra length and bulk
      to the flap at the alar rim and using topical nitroglycerin and triamcinolone
      injections when indicated. The steps outlined can help to create a more elegant
      and consistent result in PMFF nasal reconstruction.

PMID- 21856536
TI  - Use of makeup, hairstyles, glasses, and prosthetics as adjuncts to scar
      camouflage.
AB  - Scars after facial trauma or surgery can be a source of distress for patients,
      and facial plastic surgeons are frequently called upon to help manage them.
      Although no technique can remove a scar, numerous treatment modalities have been
      developed to improve facial scar appearance with varying levels of invasiveness.
      This article reviews techniques that camouflage scars without surgical
      intervention. Topical scar treatments, camouflage cosmetics, use of hairstyling
      and glasses, and facial prosthetics are discussed. In addition, professional
      counseling is provided on selection and application of topical cosmetics for use
      as part of an office practice.

PMID- 21856537
TI  - Proper care of early wounds to optimize healing and prevent complications.
AB  - Proper wound care has broad applications for all clinicians. Much of the future
      direction for enhancing wound repair focuses on key cells and growth factors,
      which is why possessing a strong understanding of the basic physiology of wound
      healing is imperative. This article first provides a thorough review of the
      phases of wound healing followed by a discussion on the latest wound management
      strategies. Wound conditions and surgical techniques are important components for
      optimizing wound healing and preventing complications. Special consideration has
      been given to the unique settings of contaminated wounds, open wounds, or avulsed
      tissue.

PMID- 21856538
TI  - Keloids: prevention and management.
AB  - Keloids result from an abnormal wound-healing process in which the normal
      regulatory pathways during tissue regeneration and scar remodeling are disrupted.
      While the pathogenesis of keloids continues to be investigated, numerous
      treatment options exist. Although prevention of keloid formation is the best
      management, early recognition of keloid formation is integral in treatment and
      prevention of recurrence. Surgical resection with adjuvant silicone gel sheeting
      or triamcinolone injection is common, but can still result in recurrence. New
      treatments include chemotherapeutics such as 5-fluorouracil, bleomycin, and
      mitomycin C. Although further clinical investigation is required for newer
      treatments, initial results are promising.

PMID- 21856539
TI  - Enhancement of facial scars with dermabrasion.
AB  - This article describes the physiology of wound healing, discusses considerations
      and techniques for dermabrasion, and presents case studies and figures for a
      series of patients who underwent dermabrasion after surgeries for facial trauma.

PMID- 21856540
TI  - Laser treatment for improvement and minimization of facial scars.
AB  - Cutaneous injuries that result in scar formation are relatively common, leading
      patients to seek treatment for cosmetic or functional improvement. Treatments
      that have the potential to improve or eliminate scarring include radiation
      therapy, surgical excision, and intralesional injections of corticosteroids, 5
      flourouracil, or bleomycin. Unfortunately, these methods are associated with high
      recurrence rates and untoward sequelae such as skin atrophy, dyspigmentation, and
      pain. Laser scar revision is a safe procedure with clinically demonstrable
      efficacy and minimal side effects when used alone or in combination with other
      scar treatments. The specifics of current laser scar revision techniques are
      addressed in this overview.

PMID- 21856541
TI  - Use of lasers in acute management of surgical and traumatic incisions on the
      face.
AB  - This article is a clinically practical review structured around the specific
      applications of laser technologies used in acute management of soft tissue
      injuries in surgical incisions and trauma. Surgical and traumatic incisions and
      injuries provide the clinician with the unique opportunity to follow the
      progression and maturation of the wound healing response from a very early stage.
      There has been a recent interest in early cosmetic optimization of surgical and
      traumatic wounds on the face using optical technologies. Early clinical results
      for acute laser intervention starting immediately after suture removal or the
      first several weeks after repair have been very promising.

PMID- 21856543
TI  - Use of hair grafting in scar camouflage.
AB  - Loss of hair-bearing tissue in the head and neck area can result from surgery,
      trauma, burns, tumors, and infection, as well as a diversity of inflammatory
      conditions, and the resulting defect can present a challenging problem for the
      reconstructive surgeon. Hair transplantation can be used as a reconstructive
      method alone or in conjunction with other techniques. The current method of using
      follicular unit grafts has led to natural restorations for a variety of areas
      including not only the scalp but also eyebrows, eyelashes, and beard areas.
      Camouflage provided by hair grafts can provide restoration not obtainable with
      other methods.

PMID- 21856542
TI  - Topical modalities for treatment and prevention of postsurgical hypertrophic
      scars.
AB  - There is no universally accepted treatment regimen and no evidence-based
      literature to guide management of hypertrophic scars. This article summarizes the
      existing literature regarding topical treatments such as silicone gel sheeting
      and ointment, onion extract, vitamin E, pressure garment therapy, massage
      therapy, and topical imiquimod 5% cream in the management of hypertrophic scars.

PMID- 21856544
TI  - Adolescent endometriosis: improving the comfort level of health care providers
      treating adolescents with endometriosis.

PMID- 21856545
TI  - Helping "adult gynecologists" diagnose and treat adolescent endometriosis:
      reflections on my 20 years of personal experience.

PMID- 21856546
TI  - Scientific investigation of endometriosis among adolescents.
AB  - The scientific literature on endometriosis specific to the adolescent population
      is limited, and the existing data are retrospective and descriptive in nature. It
      is possible that the disease has a different pathophysiology in adolescents, but
      little epidemiologic or molecular data exist to support or refute this
      speculation. In addition, the limited literature does not yet confirm that
      intervening in the adolescent population prevents long-term sequelae such as pain
      and infertility as adults. Case-control and cohort studies to identify risk
      factors, as well as prospective observational and intervention studies to assess
      treatment outcome, are required to further knowledge about endometriosis in the
      adolescent population. The scientific literature on endometriosis specific to the
      adolescent population is limited, and the existing data are retrospective and
      descriptive in nature. This review summarizes studies that have been done to date
      and suggests areas for future investigation.

PMID- 21856547
TI  - Treating endometriosis in adolescents: does it matter?
AB  - Endometriosis has major physical and psychosocial impacts on teens, as well as
      long-term implications for their health. The hidden suffering of millions of
      adolescents worldwide calls on the medical profession to respond, despite the
      challenges. Given the increasing understanding of adolescent endometriosis,
      treating adolescents with endometriosis can be a most rewarding experience.
      Moreover, diagnosing and treating the disease early could prevent more
      complicated disease later, as well as comorbidities. Helping these girls may save
      them, their families, and their communities much physical and emotional pain, as
      well as lessen the huge burden on our health care systems and society.

PMID- 21856548
TI  - Markers of adult endometriosis detectable in adolescence.
AB  - Endometriosis, a disease of young females that is possibly a devastating ailment
      requiring surgery, appears to be associated with certain features encountered in
      adolescence. First among these symptoms is the history of severe and lasting
      dysmenorrhea at the time of adolescence and the need to use oral contraceptives
      (OCs) for alleviating dysmenorrhea that failed to respond to nonsteroidal anti
      inflammatory drugs (NSAIDs). Further awareness about existing associations
      between certain symptoms experienced at adolescence and the later development of
      endometriosis is important. Indeed, the possibility of diagnosing endometriosis
      earlier when suggested by clinical history could lead to less extensive surgery
      and thus, less damage. Experimental verification of this insight, however, is
      needed before the concept that early diagnosis means lesser destructive surgery
      can be ascertained.

PMID- 21856550
TI  - Bortezomib-induced tumor lysis syndrome in a patient with HIV-negative
      plasmablastic lymphoma.
AB  - Plasmablastic lymphoma (PBL) is an aggressive lymphoma classified by the World
      Health Organization as a subtype of diffuse large B-cell lymphoma that shares
      many morphologic and immunophenotypic features with multiple myeloma. It is
      extremely rare in immunocompetent patients. Because of the small number of
      patients reported, this rare lymphoma remains a poorly characterized and
      understood entity with presently no standard recommendations regarding the
      optimal treatment. Herein, we report a dramatic clinical response coupled with
      tumor lysis syndrome to a bortezomib-based treatment in an HIV-negative patient
      with refractory plasmablastic lymphoma.

PMID- 21856551
TI  - Acute promyelocytic leukemia in HIV-infected adults: a case report and review of
      therapeutic considerations.
AB  - The incidence of acute promyelocytic leukemia (APL) in patients with HIV is
      exceedingly rare, making the establishment of therapeutic approaches challenging
      and often individualized. We report the case of a 43-year-old female who
      presented with fatigue and malaise, and was concurrently diagnosed with APL and
      HIV. Induction and consolidation with all-trans-retinoic acid (ATRA), idarubicin,
      and mitoxantrone were initiated in conjunction with highly active anti-retroviral
      therapy (HAART) consisting of tenofovir/emtricitabine, fosamprenavir, and
      raltegravir. A complete morphologic, cytogenetic, and molecular response was
      achieved post-induction. Therapeutic strategies should consider overlapping
      effects of current agents in targeting both pathologies. ATRA has been found to
      induce apoptosis in HIV-infected leukemic cells, and protease inhibitor therapy
      has furthermore been reported to be synergistic with ATRA in inducing
      differentiation of APL cell lines. Pending further investigation, regimens with
      protease inhibitor backbones may represent a viable first-line strategy for
      patients elected to receive HAART in addition to ATRA and standard chemotherapy.

PMID- 21856552
TI  - Post-treatment bone marrow residual disease > 5% by flow cytometry is highly
      predictive of short progression-free and overall survival in patients with
      Waldenstrom's macroglobulinemia.
AB  - To assess the value of bone marrow (BM) assessment by flow cytometry FCM after
      therapy in the clinical outcome of WM patients, we analyzed 42 WM patients who
      were evaluated before and after therapy. Patients were studied with a panel that
      always included the CD19, CD22, CD25, and kappa/lambda light chain immunoglobulin
      monoclonal antibodies. The mean of abnormal B-cells in the pre-therapeutic BM was
      17.8% +/- 12.1%, which decreased was after therapy to 5.4% +/- 0.7% (P = .049). A
      linear correlation was seen between the better quality of response and the
      reduction in the tumor B-lymphocyte counts at the BM, since the ratio of abnormal
      B cells between pre and posttherapy BM was 1172.17, 221.64, 3.37, 1.03, and 0.56
      for responses complete, partial, minor, stable disease and progression,
      respectively (P < .001). Intensive and rituximab-containing therapies correlated
      with deeper tumor cell reductions. Finally, the B-cell decrease correlated with
      the better overall and progression-free survival.

PMID- 21856553
TI  - Matrix metalloproteinase-8 is overexpressed in Waldenstrom's macroglobulinemia
      cells, and specific inhibition of this metalloproteinase blocks release of
      soluble CD27.
AB  - Soluble CD27 (sCD27) is produced by Waldenstrom's macroglobulinemia (WM) cells,
      with high levels found in WM patients which may facilitate disease expansion.
      Matrix metalloproteinases (MMP) may facilitate sCD27 release by cleavage of CD27.
      By gene expression analysis, we observed significantly higher transcription
      levels of MMP-8 and MMP-9, with 58.5 and 16.7 fold increase in mean transcription
      levels in WM cells relative to healthy donor peripheral blood B cells (P = .04,
      and .05, respectively). We developed a model for study of sCD27 release by
      transfecting BCWM.1 WM cells and BL2126 lymphoblastic B cells, both of which
      express MMP-8 and MMP-9 with a vector expressing FLAG-tagged CD27 (pFLAG-CD27)
      which in the presence of phorbol myristate acetate resulted in >= 10-fold
      increase in sCD27 release. MMP inhibitors against MMP-8, but not MMP 2, 3, or 9
      blocked release of sCD27. The results suggest that MMP-8 may play a role in the
      pathogenesis of WM, and that its inhibition may be of therapeutic value in WM.

PMID- 21856554
TI  - Heterogeneity of histological transformation events in Waldenstrom's
      macroglobulinemia (WM) and related disorders.
AB  - Histological transformation, typically to diffuse large B-cell lymphoma (DLBCL)
      is reported to occur in 5%-10% of patients with WM and recent studies have
      highlighted a possible aetiological role for the nucleoside analogues. It is
      however becoming increasingly clear that histological transformation is a complex
      phenomenon and may include clonally unrelated disorders. In order to highlight
      this pathological heterogeneity we describe 5 patients with diverse histological
      progression events. These included EBV-associated events namely DLBCL, peripheral
      T-cell lymphoma and spontaneously resolving mucocutaneous ulcer. A further 2
      patients demonstrated a localised plasma cell rich lesion simulating plasmacytoma
      and a de novo DLBCL arising in an unrelated B-cell clone. It is clear therefore
      that detailed pathological assessments are required in all suspected cases of
      transformation and that the pathological heterogeneity demonstrated by this study
      needs to be taken into account when potential aetiological factors are being
      assessed.

PMID- 21856555
TI  - Novel diagnostic approaches in Bing-Neel syndrome.
AB  - The central nervous system (CNS) manifestations of Waldenstrom's
      macroglobulinemia (WM) are known as the Bing-Neel syndrome (BNS). Patients with
      BNS can be classified into Group A and Group B based on the presence of
      lymphoplasmacytoid (LMP) cells within the brain parenchyma, leptomeninges, dura,
      and/or cerebrospinal fluid (CSF). To identify characteristic imaging findings for
      both Group A and Group B patients, we reviewed all 36 cases (26 referenced, 10
      unreported) of proven WM with CNS symptoms, CSF analysis and/or biopsy, and
      magnetic resonance imaging (MRI) of the brain and/or spinal cord. Enhancement on
      MRI suggests invasion of the central neuraxis by LMP cells, and can help
      distinguish between Group A and Group B patients. In addition to differentiating
      true WM lesions in the CNS from ischemia, hyperviscosity events, and
      demyelinating lesions, evaluation of brain and spinal cord with gadolinium
      enhanced MRI has the potential to guide management.

PMID- 21856556
TI  - MDCT evaluation of the growth kinetics of serous and benign mucinous cystic
      neoplasms of the pancreas.
AB  - We assessed the growth kinetics of pathologically proven benign neoplastic cystic
      lesions of the pancreas. The volume and longest axial diameter (LAD) of 20
      pathologically proven pancreatic cystic lesions (12 mucinous cystic neoplasms
      (MCN) and 8 serous cystadenomas (SCN)) on 2 multidetector computed tomography
      scans, obtained before resection, were measured. Reciprocal of doubling time,
      doubling time and growth rate based on volume and LAD were calculated. A P value
      <0.05 was considered significant. For all cysts, growth kinetics based on volume
      were: reciprocal of doubling time (mean = 3.03, median=1.0), doubling time (mean
      = 644, median = 388 days) and growth rate (mean = 74.7, median = 5.7 ml/year).
      Results based on LAD were: reciprocal of doubling time (mean = 3.09, median =
      1.3), doubling time (mean = 752, median = 273 days) and growth rate (mean = 24.5,
      median = 5.6 mm/year). These variables were not statistically different between
      MCNs and SCNs (P > 0.05 in all instances). Reciprocal of doubling time based on
      volume and LAD were comparable (P > 0.05). We concluded that the mean reciprocal
      of doubling time was 3.03 and 3.09 using volume and LAD, respectively. This may
      aid in designing follow-up guidelines for pancreatic cysts.

PMID- 21856557
TI  - Soluble biomarkers in psoriasis.
AB  - Psoriasis is a common, chronic, recurrent skin disorder, characterized by
      keratinocyte proliferation, T-cell activation and angiogenesis. The results of
      various clinical and experimental studies indicate that psoriasis is a complex,
      multifactorial disease with a genetic predisposition. During the past few years,
      many studies related to psoriasis biomarkers have been conducted. Biomarkers can
      relate to diagnosis, pathogenesis, prognosis, or therapeutic response. They could
      provide insight into disease susceptibility and natural history. The
      identification of biomarkers related to co-morbidities in psoriasis, such as
      arthritis, cardiovascular disease and the metabolic syndrome, has attracted
      special interest. This review presents current knowledge of soluble biomarkers in
      psoriasis, including cytokines, chemokines, pro-angiogenic mediators, growth
      factors, antimicrobial proteins, neuropeptides and markers of oxidative stress.

PMID- 21856558
TI  - Extensive acantholysis as the major histological feature of a severe case of
      Dowling Meara-epidermolysis bullosa simplex: a reappraisal of acantholysis in the
      newborn.
AB  - Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders
      characterized by blistering and skin fragility secondary to mechanical trauma.
      Epidermolysis bullosa simplex (EBS) is the most frequent form of EB, with Dowling
      Meara (DM-EBS) subtype being the most severe form in this group. Conventional
      histopathological evaluation is usually of low value in the diagnosis of EB, and
      significant histological features have rarely been reported in this group of
      diseases. We describe a case of severe DM-EBS in which acantholysis was observed
      in the histological examination. This finding led us to consider other diagnoses,
      such as neonatal pemphigus vulgaris or lethal acantholytic EB. Histological,
      immunological, ultrastructural and genetic tests were performed, leading to a
      final diagnosis of DM-EBS. Therefore, we believe that DM-EBS should be considered
      in the differential diagnosis of a newborn with blisters, where acantholysis is
      the main histological feature.

PMID- 21856559
TI  - Effect of narrow band ultraviolet B on survivin in psoriatic skin lesions.
AB  - BACKGROUND: Suppression of apoptosis is responsible for epidermal thickness in
      psoriasis. Survivin is an anti-apoptotic protein that can be modulated by
      ultraviolet B (UVB). AIM: Our aim was to investigate the role of survivin in
      psoriasis and to evaluate the effect of narrow band (NB)-UVB on the survivin
      levels in psoriatic lesions. METHODS: This study included 20 psoriatic patients
      and 20 healthy controls. Patients were treated with 24 sessions of NB-UVB. Skin
      biopsies were taken from the affected skin of each patient before and after
      treatment, and from the controls, to examine survivin levels by ELISA. RESULTS:
      Survivin was significantly upregulated in psoriasis compared to controls
      (p<0.001). We found significant positive correlations between survivin levels
      before therapy and the extent of body involvement (r=0.675, p=0.002), as well as
      the PASI score (r=0.67, p=0.001). A significant decrease in survivin levels was
      observed post treatment compared to baseline levels (p<0.001). CONCLUSION: We
      found increased survivin levels in psoriasis and a significant reduction
      following NB-UVB induced clinical improvement of psoriasis.

PMID- 21856560
TI  - Chronic papular urticaria due to pigeon ticks in an adult.

PMID- 21856561
TI  - Rapid response of scalp psoriasis to ustekinumab.

PMID- 21856562
TI  - Acute generalized exanthematous pustulosis induced by topical diphenhydramine.

PMID- 21856563
TI  - Lupus vulgaris diagnosed 62 years after onset.

PMID- 21856564
TI  - Rash as the first manifestation of acute graft-versus-host disease after
      orthotopic liver transplantation.

PMID- 21856565
TI  - Safety, not only efficacy still to be proven for controversial new MS treatment.

PMID- 21856566
TI  - Treating intellectual disability; look for creatine peaks in the brain.

PMID- 21856567
TI  - Helping the FTD patient-caregiver dyad.

PMID- 21856568
TI  - Delirium: a review.
AB  - Delirium affects a diverse patient population, may present with highly variable
      clinical features, is a source of distress for patients and their caregivers,
      prolongs hospital stays and may herald a poor prognosis. Many cases of delirium
      are reversible and therefore a full history, physical examination and
      investigations should be performed. Ahigh degree of suspicion is required for
      detecting delirium and thorough investigations are necessary in order to
      determine the underlying etiology and to maximize the potential for
      reversibility. The following review outlines important aspects of a clinical
      approach to delirium, the differential diagnosis of delirium, investigation of a
      patient presenting with delirium, management of delirium, the pathophysiology of
      delirium and the prognosis accompanying delirium.

PMID- 21856569
TI  - Consciousness and cell memory: a dynamic epigenetic interrelationship.
AB  - There have been great advances in the neurological sciences in recent years
      including some in the higher functions of the brain such as memory but one of the
      more critical of these with close ties to memory is consciousness which remains
      an enigma. Revolutionary developments in genetics during the last two decades,
      referred to as epigenetics, have provided opportunity for discovery. The
      chromatin in the cell nucleus consists mainly of DNA nucleotides and histone
      proteins and the DNA is dynamically and epigenetically altered by the local
      actions of enzymes and trans-acting factors on the adjacent histone amino acids.
      DNA is also directly activated or inhibited by methyl groups and by non-coding
      RNAs. Epigenetics is a determinant in long-term cell memory consolidation and, as
      recently demonstrated in animal and human studies and described here, these
      effects enable a rapid and extraordinarily complex cognitive matching of cell
      memory to experience during consciousness.

PMID- 21856570
TI  - Rabies in the critical care unit: diagnostic and therapeutic approaches.
AB  - Worldwide, human rabies is prevalent where there is endemic dog rabies, but the
      disease may present unexpectedly in critical care units when suggestive clinical
      features have passed. In North America transmission from bats is most common and
      there is often no history of a bat bite or even contact with bats. Laboratory
      diagnostic evaluation for rabies includes serology plus skin biopsy,
      cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA
      detection. Rare patients have survived rabies, and most received rabies vaccine
      prior to the onset of illness. Therapeutic coma (midazolam and phenobarbital),
      ketamine, and antiviral therapies (dubbed the "Milwaukee Protocol") were given to
      a rabies survivor, but this therapy was likely not directly responsible for the
      favorable outcome. There have been many subsequent failures of similar
      therapeutic approaches. There is no scientific rationale for the use of
      therapeutic coma in human rabies. New approaches to treating human rabies need to
      be developed.

PMID- 21856571
TI  - Neuroscience in Nazi Europe part I: eugenics, human experimentation, and mass
      murder.
AB  - The Nazi regime in Germany from 1933 to 1945 waged a veritable war throughout
      Europe to eliminate neurologic disease from the gene pool. Fueled by eugenic
      policies on racial hygiene, the Nazis first undertook a sterilization campaign
      against "mental defectives," which included neurologic patients with epilepsy and
      other disorders, as well as psychiatric patients. From 1939-41 the Nazis instead
      resorted to "euthanasia" of many of the same patients. Some neuroscientists were
      collaborators in this program, using patients for research, or using extracted
      brains following their murder. Other reviews have focused on Hallervorden, Spatz,
      Schaltenbrand, Scherer, and Gross, but in this review the focus is on
      neuroscientists not well described in the neurology literature, including Scholz,
      Ostertag, Schneider, Nachtsheim, and von Weizsacker. Only by understanding the
      actions of neuroscientists during this dark period can we learn from the slippery
      slope down which they traveled, and prevent history from repeating itself.

PMID- 21856572
TI  - Causes for treatment delays in dystonia and hemifacial spasm: a Canadian survey.
AB  - BACKGROUND: Dystonia must be accurately diagnosed so that treatment can be
      administered promptly. However, dystonia is a complex disorder, with variable
      presentation, which can delay diagnosis. METHODS: Data were gathered by
      questionnaire from 866 patients with dystonia or hemifacial spasm (HFS) treated
      in 14 movement disorders centres in Canada injecting botulinum toxin, to better
      understand the path to diagnosis, wait times and obstacles to treatment. RESULTS:
      Most participants were female (64.1%), mean age was 58 years, and patients
      consulted an average of 3.2 physicians before receiving a dystonia or HFS
      diagnosis. Many patients (34%) received other diagnoses before referral to a
      movement disorders clinic, most commonly "stress" (42.7%). A variety of
      treatments were often received without a diagnosis. The mean lag time between
      symptom onset and diagnosis was 5.4 years. After the decision to use botulinum
      toxin, patients waited a mean of 3.1 months before treatment. The most common
      diagnoses were cervical dystonia (51.6% of patients), HFS (20.0%) and
      blepharospasm (9.8%). CONCLUSIONS: Survey results show that diagnosis of
      dystonias or of HFS, and therefore, access to treatment, is delayed. An
      educational program for primary care physicians may be helpful to decrease the
      time to diagnosis and referral to a specialist centre for treatment.

PMID- 21856573
TI  - Revascularization for complex cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: Complex cerebral aneurysms may require indirect treatment
      with revascularization. This manuscript describes various surgical
      revascularization techniques together with clinical outcomes. METHODS: Thirty-two
      consecutive patients with complex cerebral aneurysm were managed from November
      2005 to October 2008. Techniques used for revascularization were high-flow
      bypass, low-flow bypass, branch artery reimplantion, and primary reanastomosis.
      Physiologic and anatomic monitoring technologies, including
      electroencephalography, somatosensory evoked potential monitoring, microvascular
      doppler ultrasonography, and/or indocyanine green videoangiography were used
      intraoperatively to assess both brain physiology and vascular anatomy. Patient
      outcome was determined using the Glasgow Outcome Scale at discharge and at a mean
      of 12 months post operation (range 6-25 months). RESULTS: Two cervical carotid
      aneurysms (6%) were resected followed by primary reanastomosis, 21 aneurysms
      (66%) were trapped following saphenous vein high-flow bypasses, five (16%) were
      clipped after superficial temporal or occipital artery low-flow bypasses, and
      four (12%) middle cerebral branch arteries were reimplanted. Of the 32 patients
      at discharge, 29 (91%) had a Glasgow Outcome Scale of four or five, two (6%) had
      severe disability, and one (3%) died. CONCLUSION: Cerebral revascularization
      remains an effective and reliable procedure for treatment of complex cerebral
      aneurysms. Low morbidity and mortality rates reflect the maturity of patient
      selection and surgical technique in the management of these lesions.

PMID- 21856574
TI  - Prevalence of childhood epilepsy in Canada.
AB  - RATIONALE: Few data exist on the frequency and burden of childhood epilepsy in
      Canada and on the impact in the general population. We have assessed the point
      prevalence of childhood epilepsy in Canada. METHODS: We analyzed data from the
      National Longitudinal Survey of Children and Youth (N=20 025 for Cycle 2, and N=
      31 960 for cycle 3). Each cycle was collected over a two year period (2: 1996
      1997, 3: 1998-1999). In the survey the following specific question was asked to
      the person most knowledgeable in the household: "Does the child have any of the
      following long-term conditions that have been diagnosed by a health
      professional?" The list of responses included Epilepsy and certain co-morbid
      conditions. In addition, a subsequent question identified whether the condition
      was treated by means of a specific anticonvulsant medication. (anticonvulsants or
      anti-epileptic pills?). Prevalence was based on the national standard population
      at the time of each survey. RESULTS: In Cycle 2, 80 of 20 025 subjects from 0 to
      13 years old were described to have the diagnosis of epilepsy, yielding a
      weighted point prevalence of 4.03 per 1 000. In Cycle 3 161 of 31 960 children
      from 0 to 15 were described as having epilepsy, yielding a weighted point
      prevalence of 5.26 per 1 000. The rate of epilepsy was higher for males and
      increases with age. CONCLUSION: The overall rates for this age cohort are
      consistent with those obtained in other developed countries and seem to coincide
      with rates for youth and adults in Canada.

PMID- 21856575
TI  - Depiction of seizure first aid management in medical television dramas.
AB  - OBJECTIVES: The objective of this study was to investigate whether medical
      television dramas portray proper seizure first aid. METHODS: Episodes of the four
      highest-rated US medical dramas ("Grey's Anatomy," "House M.D.", "Private
      Practice," and "ER") were screened for the presence of seizures. "Patient" age,
      sex, semiology, and etiology were recorded. The appropriateness of seizure first
      aid management was determined by comparison to the Epilepsy Foundation of America
      (EFA) guidelines. RESULTS: Among 364 television programs, 65 seizures (in 59
      individuals) were identified (30 males; 29 females). Seizures were primary or
      secondarily generalized tonic-clonic in 53 (81.5%) cases. Other seizure types
      included complex partial (5, 7.7%), simple partial (1, 1.5%), myoclonic (1,
      1.5%), absence (1, 1.5%), and psychogenic (1, 1.5%). On 63 occasions (96.9%),
      first aid was performed by a health care professional. First aid management was
      judged appropriate in 21 (32.3%) seizures, inappropriate in 28 (43.1%), and
      indeterminate in 16 (24.6%). Inappropriate practices included holding the person
      down (17, 26.2%), trying to stop the involuntary movements (10, 15.4%) and
      putting something in the person's mouth (11, 16.9%). CONCLUSIONS: The first aid
      management of seizures performed by actors portraying health care professionals
      was inappropriate in nearly half of all cases. Inaccurate depiction of seizure
      first aid management may contribute to misinformation of the general public. The
      television industry could easily incorporate the simple first aid EFA seizure
      guidelines as a public service without sacrificing dramatic impact.

PMID- 21856576
TI  - Impact of the cognitive status on the memory complaints in MS patients.
AB  - OBJECTIVE: Despite the evidence of cognitive deficits in Multiple Sclerosis (MS)
      patients, evaluation of their cognitive integrity is often limited to the use of
      clinical interviews and questionnaires. However, the consensus in the literature
      is that these patients under- or overestimate their deficits and repercussions.
      The objective of this study was to clarify why some patients overestimate while
      others underestimate their memory deficits. METHOD: Fifty-four participants (30
      MS, 24 controls) completed the Prospective and Retrospective Memory Questionnaire
      (PRMQ) and were tested on a battery of neuropsychological tests. Based on the
      test results, MS patients were categorized as having either mild or
      moderate/severe cognitive deficits. RESULTS: The moderate/severe MS group
      differed from the two other groups on the Rey Auditory Verbal Learning Test
      (RAVLT) but did not differ from the control group on the PRMQ. Conversely, the
      mild MS group did not differ from the control group on the RAVLT but did report
      significantly more problems than this group on the PRMQ. There was no difference
      between the two clinical groups on the Depression Index (Beck) but there was a
      significant correlation (r=.409) between the depression scores and the
      overestimation of prospective memory problems (PRMQ). CONCLUSION: The results
      explain the contradiction in the literature. It is the mild group who
      overestimates, maybe because they are overly concerned by their deficits, whereas
      the cognitive impairments of the moderate/severe group lead them to underestimate
      and may make their self-assessment unreliable. Formal testing or information from
      a significant other would be advisable.

PMID- 21856577
TI  - Cyst formation following radiosurgery for AVMs: report of 3 cases.
AB  - BACKGROUND: Stereotactically-focused radiosurgery (SRS) for the treatment of
      arteriovenous malformations (AVM) has been in widespread use for over two
      decades. Over this timeframe the indications for treatment, standardization of
      radiation dosage, and the results expected from treatment have been elaborated.
      Less well known are the long-term complications associated with SRS. We report
      three patients who had SRS for the treatment of AVM who developed a cyst at the
      site of treatment as a late complication. METHODS: From 201 patients treated by
      SRS for an AVM, three developed a cyst at the treatment site. Their clinical
      presentation, the characteristics of the AVMs and the treatment were reviewed, as
      well as similar cases gleaned from the literature. RESULTS: Three women, aged 28
      43 years, had an AVM treated by: craniotomy and clipping of arterial feeders
      followed by SRS, by craniotomy for resection followed by SRS or by endovascular
      embolization and SRS. The patients did well following treatment but two of them
      developed a symptomatic and the other an asymptomatic cyst at the treatment site
      3-19 years later. The symptomatic patients underwent marsupialization of the cyst
      and the other is under observation. CONCLUSION: Stereotactic radiosurgery is an
      established and safe treatment for patients with AVMs. Delayed cyst formation can
      occur many years after treatment and long term follow-up is indicated in patients
      whose AVM has been treated with SRS.

PMID- 21856578
TI  - Complications in MS patients after CCSVI procedures abroad (Calgary, AB).
AB  - BACKGROUND: The "chronic cerebrospinal venous insufficiency" or "CCSVI"
      hypothesis, namely that multiple sclerosis (MS) is caused by abnormalities in the
      azygous and internal jugular veins with subsequent alterations in venous
      hemodynamics in the central nervous system, has been a dominant topic in MS care
      in Canada over the past year. Although there is no methodologically rigorous
      evidence to support this hypothesis presently, a considerable number of MS
      patients have undergone endovascular CCSVI procedures. Such procedures include
      angioplasty or stent placement in jugular and azygous veins. The safety and
      efficacy of these procedures is unknown, but not without risk. METHODS: Chart and
      patient review of five patients with confirmed MS followed in Calgary were
      undertaken after patients came to medical attention by referral or admission
      secondary to complications believed to be associated with CCSVI procedures.
      RESULTS: Complications upon investigation and review included internal jugular
      vein stent thrombosis, cerebral sinovenous thrombosis, stent migration, cranial
      nerve injury and injury associated with venous catheterization. CONCLUSIONS: As
      the debate about CCSVI and its relationship to MS continues, the complications
      and risks associated with venous stenting and angioplasty in jugular and azygous
      veins are becoming clearer. As increasing numbers of MS patients are seeking such
      procedures, these five cases represent the beginning of a wave of complications
      for which standardized care guidelines do not exist. Our experience and that of
      our colleagues will be used to develop guidelines and strategies to monitor and
      manage these patients as their numbers increase.

PMID- 21856580
TI  - An international needs assessment of caregivers for frontotemporal dementia.
AB  - OBJECTIVE: To guide development of public awareness and caregiver support
      resources for frontotemporal dementia (FTD) syndromes. METHODS: We used an online
      survey to explore their needs. The survey was self-administered by self
      identified, English-speaking caregivers for patients with FTD in several
      countries. RESULTS: Of 79 caregiver respondents, approximately half were caring
      for patients with behavioural variant FTD or semantic dementia. The most common
      initial symptoms were Changes in Thinking and Judgment. Half of the respondents
      identified "failure to recognize the early stage of illness as a dementia" as the
      most troublesome aspect. Accordingly, over 40% of respondents had difficulty
      obtaining an accurate diagnosis for the patient. Caregivers prioritized family
      counseling and the public educational message that dementia can affect young
      people. CONCLUSION: The largest international survey of FTD caregivers to-date
      showed that support is needed for all family members adapting to the shock of
      early-onset dementia, and this may be most readily provided online.

PMID- 21856579
TI  - Founder mutation for alpha-sarcoglycan-LGMD2D in a Magdalen Islands Acadian
      cluster.
AB  - BACKGROUND: We have recruited a group of four living and reviewed the records of
      six deceased distantly related French-Canadians of Acadian descent affected by a
      childhood-onset form of recessive limb-girdle muscular dystrophy (LGMD). All
      cases originate from the small archipelago of the Magdalen Islands (population:
      13,000) isolated in the Gulf of St-Lawrence. METHODS: Based on the likely sharing
      of the same founder mutation we completed a 319K SNPs genome-wide scan to
      identify the disease locus and then screen candidate genes in this region.
      RESULTS: All patients had normal initial motor milestones. They presented with
      limb girdle weakness at the average age of seven years (5-11). Progressive
      weakness led to loss of ambulation at a wide range of ages (10-39). Patients also
      developed macroglossia, large calves and mild to moderate contractures,
      hyperlordosis and decreased pulmonary function. Creatine kinase levels were
      elevated (1,800-10,000 U/L) in the first decades, but decreased with progression
      of disease. Homozygosity mapping uncovered a shared chromosomal region of 6.33Mb.
      The alpha sarcoglycan (SGCA) gene, mutated in LGMD2D, lay in this candidate
      interval. Sequencing of all SGCA exons uncovered a shared homozygous missense
      mutation (c. 229C>T, p.R77C), the most common SGCA mutation internationally
      reported. Using demographic data, we estimated a high carrier rate of 1/22.
      CONCLUSION: The p.R77C mutation has also been observed in many populations,
      including in France and Spain (Basques). This corresponds to the first reported
      recessive founder disease for the Magdalen Islands, an archipelago settled in the
      XIXth century, largely by Acadian immigrants.

PMID- 21856581
TI  - Widespread symmetrical subcortical band heterotopia.

PMID- 21856582
TI  - Persistant anterior falcine sinus: demonstration by CT angiography.

PMID- 21856583
TI  - Missing Huntington's disease for tardive dyskinesia: a preventable error.

PMID- 21856584
TI  - Creatine deficiency syndromes: diagnostic pearls and pitfalls.

PMID- 21856585
TI  - OFF-rebound dyskinesia in subthalamic nucleus stimulation in Parkinson disease.

PMID- 21856586
TI  - Glucocerebrosidase mutations in a French-Canadian Parkinson's disease cohort.

PMID- 21856587
TI  - Multiple brain cysts: an unusual form of demyelinating disease.

PMID- 21856588
TI  - New anticoagulants for atrial fibrillation: the beginning of a a new era in
      stroke prevention.

PMID- 21856589
TI  - Health research funding in crisis.

PMID- 21856590
TI  - More than 'answers we can use', we need to ask the right questions. Re: Pelz D.
      CURES and the dilemma of unruptured intracranial aneurysms. Can J Neuro Sci. 2011
      Mar;38(2):191-2.

PMID- 21856591
TI  - Ingestion of large amounts of papaya fruit and impaired effectiveness of
      levothyroxine therapy.

PMID- 21856593
TI  - Vitamin D, calcium, and cardiovascular mortality: a perspective from a plenary
      lecture given at the annual meeting of the American Association of Clinical
      Endocrinologists.
AB  - OBJECTIVE: To examine data showing associations between serum 25-hydroxyvitamin D
      levels and calcium intake and cardiovascular mortality. METHODS: The articles
      reviewed include those published from 1992-2011 derived from search engines
      (PubMed, Scopus, Medscape) using the following search terms: vitamin D, calcium,
      cardiovascular events, cardiovascular mortality, all-cause mortality, vascular
      calcification, chronic kidney disease, renal stones, and hypercalciuria. Because
      these articles were not weighted (graded) on the level of evidence, this review
      reflects my own perspective on the data and how they should be applied to
      clinical management. RESULTS: For skeletal health, vitamin D and calcium are both
      needed to ensure proper skeletal growth (modeling) and repair (remodeling).
      Nutritional deficiencies of either vitamin D or calcium may lead to a spectrum of
      metabolic bone disorders. Excessive consumption of either nutrient has been
      linked to a variety of medical disorders, such as hypercalcemia or renal stones.
      There have also been associations between vitamin D or calcium intake and
      cardiovascular disease. However, neither of these associations have established
      evidence nor known causality for increasing cardiovascular risk or all-cause
      mortality in patients with creatinine clearances greater than 60 mL/min. In
      patients with more severe chronic kidney disease, stronger data link excess
      calcium (or phosphorus) intake and increase in vascular calcification, but not
      mortality. The safe upper limit for vitamin D intake is at least 4000 IU daily
      and probably 10 000 IU daily; for calcium, the safe upper limit is between 2000
      and 3000 mg daily. CONCLUSIONS: While no solid scientific evidence validates that
      serum vitamin D levels between 15 and 70 ng/mL are associated with increased
      cardiovascular disease risk, stronger but inconsistent evidence shows an
      association between calcium supplementation greater than 500 mg daily and an
      increase in cardiovascular disease risk. Most professional societies suggest that
      replacement levels of these nutrients be personalized with the goal of reaching a
      25-hydroxyvitamin D concentration between 30 and 50 ng/mL and a calcium intake of
      1200 mg daily.

PMID- 21856592
TI  - Colesevelam hydrochloride added to background metformin therapy in patients with
      type 2 diabetes mellitus: a pooled analysis from 3 clinical studies.
AB  - OBJECTIVE: To evaluate the glucose- and lipid-altering efficacy of colesevelam
      hydrochloride (HCl) when added to background metformin therapy in patients with
      inadequately controlled type 2 diabetes mellitus (T2DM). METHODS: This post hoc
      analysis included patients with T2DM from 3 randomized, double-blind, placebo
      controlled pivotal studies who received metformin as part of their background
      antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly
      assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing
      metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy
      or combination therapy, wherein the combination therapies may have included
      metformin. RESULTS: In this pooled analysis of 696 patients with T2DM who were
      receiving metformin monotherapy or metformin combined with other antidiabetes
      therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to
      receive placebo. In comparison with placebo, colesevelam HCl significantly
      reduced hemoglobin A1c (A1C) and fasting plasma glucose (mean treatment
      difference: -0.50% and -15.7 mg/dL, respectively; P<.001 for both), as well as
      significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean
      treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density
      lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%)
      (P<.0001 for all). Median triglyceride levels were increased with colesevelam HCl
      (median treatment difference: +12.8%; P<.0001). In comparison with placebo,
      colesevelam HCl significantly increased apo A-I (mean treatment difference:
      +3.3%; P<.0001), whereas the mean increase in HDL-C with colesevelam HCl was not
      significant. Colesevelam HCl therapy was generally well tolerated. CONCLUSION:
      When added to metformin-including therapy, colesevelam HCl significantly reduced
      A1C and fasting glucose, as well as levels of LDL-C, TC, non-HDL-C, and apo B in
      patients with inadequately controlled T2DM.

PMID- 21856594
TI  - Assessment of the utility of the high-dose dexamethasone suppression test in
      confirming the diagnosis of Cushing disease.
AB  - OBJECTIVE: To determine the utility of high-dose dexamethasone suppression (HDDS)
      tests to confirm the diagnosis of Cushing disease (CD). METHODS: In this
      retrospective study, we reviewed medical records of patients who underwent either
      the overnight 8-mg HDDS test or the 2-day 2-mg HDDS test every 6 hours. The
      percentage suppression of morning serum cortisol and the percentage suppression
      of 24-hour urine free cortisol (UFC) were calculated. RESULTS: Of 141 patients
      with proven CD who underwent HDDS tests, 77 (55%) underwent the overnight 8-mg
      HDDS test and 64 (45%) underwent the 2-day 2-mg HDDS test every 6 hours. With the
      overnight 8-mg HDDS test, 73 of 77 patients (95%) had greater than 50%
      suppression and 48 of 77 patients (62%) had greater than 80% suppression of the
      morning serum cortisol in comparison with the baseline value. With the 2-day 2-mg
      HDDS test, only 41 of 64 patients (64%) had greater than 90% suppression of 24
      hour UFC. CONCLUSION: We conclude that the overnight 8-mg HDDS test accurately
      confirmed the diagnosis of CD with a high sensitivity of 95% with use of a
      criterion of greater than 50% suppression; in contrast, the sensitivity was only
      62% with use of a more precise cutoff of greater than 80% suppression. The 2-day
      2-mg HDDS test with a criterion of greater than 90% suppression of 24-hour UFC
      had a sensitivity of 64%. These results confirm the limited precision of the HDDS
      tests.

PMID- 21856595
TI  - Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular
      risk factors.
AB  - OBJECTIVE: To assess whether liraglutide, a glucagon-like peptide-1 receptor
      agonist, has cardioprotective properties in addition to its glycemic effects.
      METHODS: We performed a retrospective analysis of medical records of 110 obese
      patients with type 2 diabetes mellitus treated with liraglutide for at least 6
      months between March 2010 and April 2011 at our tertiary care referral center.
      The variables analyzed were body mass index, hemoglobin A(1c) (A1C), systolic
      blood pressure (SBP), plasma C-reactive protein (CRP) concentrations, and serum
      lipids. RESULTS: In our overall study cohort, we noted a reduction in mean weight
      from 120 +/- 5 kg to 115 +/- 3 kg and a decrease in mean A1C from 7.8% +/- 0.6%
      to 7.2% +/- 0.2%. The mean triglyceride concentration decreased from 173 +/- 19
      mg/dL to 151 +/- 15 mg/dL, the mean SBP was reduced from 132 +/- 6 mm Hg to 125
      +/- 4 mm Hg, and the mean CRP concentration declined from 4.7 +/- 0.8 mg/L to 3.2
      +/- 0.4 mg/L after treatment with liraglutide for a minimal duration of 6 months
      and a mean duration of 7.5 months (for all the foregoing changes, P<.05). These
      variables decreased whether these patients were previously treated with orally
      administered hypoglycemic agents alone or in combination with insulin or
      exenatide. CONCLUSION: Our findings in a clinical practice show that liraglutide
      is a potent antidiabetes drug, whether given in combination with orally
      administered agents or insulin or as a substitution for exenatide. It lowers body
      weight, A1C levels, SBP, and CRP and triglyceride concentrations.

PMID- 21856596
TI  - Effect of the diagnostic criteria of the International Association of Diabetes
      and Pregnancy Study Groups on the prevalence of gestational diabetes mellitus in
      urban Mexican women: a cross-sectional study.
AB  - OBJECTIVE: To explore the prevalence of gestational diabetes mellitus (GDM),
      defined by the previous criteria of the American Diabetes Association (ADA), as
      well as the criteria suggested by the International Association of Diabetes and
      Pregnancy Study Groups (IADPSG), in an unselected group of urban Mexican pregnant
      women and to analyze the frequency of large for gestational age (LGA) newborns in
      this same group of women with use of both diagnostic criteria. METHODS: A cross
      sectional study included 803 consecutive Mexican urban women with a singleton
      pregnancy, without concomitant diseases and no prior history of GDM, who
      underwent a 2-step screening protocol for diagnosis of GDM at admission to
      prenatal care. RESULTS: The ADA criteria identified 83 women (10.3%) whereas the
      IADPSG criteria diagnosed 242 women (30.1%) having GDM (P = .0001). Fasting
      glucose concentrations during the 100-g 3-hour oral glucose tolerance test were
      abnormal in 116 women (14.4%) and in 160 women (19.9%) on the basis of ADA and
      IADPSG criteria, respectively (P = .004). The frequency of LGA newborns was 7.4%
      based on IADPSG criteria and 6.0% based on ADA criteria-no significant difference
      (P = .64). CONCLUSION: With use of the IADPSG criteria, the prevalence of GDM
      increased almost 3-fold in comparison with that for the ADA criteria.
      Nevertheless, no significant difference was found in the prevalence of LGA
      newborns.

PMID- 21856597
TI  - "This case did not resemble any type of paroxysmal hypertension previously seen
      by us".

PMID- 21856598
TI  - Clinical markers implying the need for treatment in women with gestational
      diabetes mellitus.
AB  - OBJECTIVE: To assess the association of the point-of-care hemoglobin A1c (POC
      A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for
      medication in women with gestational diabetes (GDM). METHODS: POC A1C, FBG, and
      BMI values at GDM diagnosis and fetal weight at delivery were obtained for women
      identified from a prospective patient registry. These outcomes were compared
      between women who did not require medication for GDM and women who did require
      medication. RESULTS: Mean values of POC A1C, FBG, and BMI in 67 patients who
      required medication were higher than those in 71 patients who did not require
      medication (POC A1C: 5.72 +/- 0.45% vs 5.35 +/- 0.46% [P<.001]; FBG: 97.4 +/-
      12.3 mg/dL vs 86.4 +/- 9.5 mg/dL [P<.001]; BMI: 35.4 +/- 6.4 kg/m2 vs 30.4 +/-
      6.2 kg/m(2) [P<.001]). There was a modest correlation between POC A1C and FBG
      (Spearman rho 0.4, P<.001) and between POC A1C and BMI (Spearman rho 0.366,
      P<.001). Maternal POC A1C was not correlated with fetal weight at delivery
      (Spearman rho -0.010, P = .915). CONCLUSIONS: Higher POC A1C, FBG, and BMI values
      were associated with the need for medication in women with GDM. The use of
      clinical markers to assess glycemic control sooner in pregnancy may lead to the
      earlier identification of women at risk for GDM and earlier intervention to
      decrease the risk for complications.

PMID- 21856599
TI  - Human immunodeficiency virus-associated lipodystrophy: an objective definition
      based on dual-energy x-ray absorptiometry-derived regional fat ratios in a South
      Asian population.
AB  - OBJECTIVE: To develop an objective definition of human immunodeficiency virus
      (HIV)-associated lipodystrophy by using regional fat mass ratios and to assess
      the utility of anthropometric and skinfold measurements in the initial screening
      for lipodystrophy. METHODS: Male patients between 25 and 50 years old with proven
      HIV infection (highly active antiretroviral therapy [HAART]-naive subjects and
      those receiving successful HAART) were studied and compared with body mass index
      (BMI)-matched HIV-negative control subjects. Anthropometric variables, body
      composition, dual-energy x-ray absorptiometry findings, and metabolic variables
      were compared among the 3 study groups and between those patients with and those
      without lipodystrophy. RESULTS: Trunk fat/lower limb fat mass ratio >2.28
      identified 54.3% of patients with HIV receiving HAART as having lipodystrophy and
      had the highest odds ratio for predicting metabolic syndrome. The "clinical
      diagnosis of lipodystrophy" and the "clinical scoring system" had too many false
      positive and false-negative results. Triceps skinfold thickness (SFT)/BMI ratio
      <=0.49 and abdominal SFT/triceps SFT ratio >1.385 have good sensitivity but poor
      specificity in identifying lipodystrophy. In comparison with HAART-naive patients
      with HIV, those receiving HAART had significantly higher insulin resistance, and
      a significantly greater proportion had impaired glucose tolerance and
      dyslipidemia. Among patients receiving HAART, those with lipodystrophy had a
      greater degree of insulin resistance, higher triglyceride levels, and lower
      levels of high-density lipoprotein cholesterol. CONCLUSION: The trunk fat/lower
      limb fat mass ratio in BMI-matched normal subjects can be used to derive cutoff
      values to define lipodystrophy objectively in HIV-infected patients. Defining
      lipodystrophy in this way is better than other methods of identifying those
      patients with increased cardiovascular risk. Triceps SFT/BMI and abdominal
      SFT/triceps SFT ratios may be useful as screening tools in resource-poor
      settings.

PMID- 21856600
TI  - The Hirsute woman: challenges in evaluation and management.
AB  - OBJECTIVE: To review the etiology, pathogenesis, diagnostic approach, and
      management of hirsutism. METHODS: We discuss the clinical course of hirsutism and
      provide our recommendations on the various treatment options available. RESULTS:
      Hirsutism is a common clinical problem characterized by the presence of increased
      terminal hair growth in androgen-dependent areas of the skin. The development of
      hirsutism depends on the presence of the pilosebaceous unit, which is genetically
      determined, as well as the presence of the androgen receptor and intracellular
      5alpha-reductase activity, which converts testosterone to its more active
      metabolite, dihydrotestosterone. A detailed history and physical examination and
      the following laboratory tests can diagnose most causes of hirsutism: early
      morning follicular phase measurement of total testosterone, testosterone not
      bound to sex hormone-binding globulin, dehydroepiandrosterone sulfate, 17
      hydroxyprogesterone, prolactin, and thyrotropin levels. Oral contraceptive
      preparations may be effective monotherapy for mild hirsutism. For the treatment
      of more severe hirsutism, oral contraceptive pills combined with spironolactone
      are as effective as oral contraceptive pills containing cyproterone acetate,
      which are not available in the United States. Because of teratogenicity,
      spironolactone should be used with caution in premenopausal women when it is
      administered without an oral contraceptive pill. Metformin is an alternative
      therapy for hirsutism in women with polycystic ovary syndrome who have other
      indications for metformin use. Metformin is not as effective as antiandrogens for
      the management of hirsutism. The use of glucocorticoids, finasteride, or
      flutamide is not recommended. CONCLUSIONS: Hirsutism can be evaluated with a
      detailed history and physical examination and a limited number of hormonal tests.
      Serious disorders presenting as hirsutism are rare and can be excluded with the
      recommended evaluation. Treatment is targeted at reducing the production and
      bioavailability of testosterone, as well as blocking target tissue androgen
      action.

PMID- 21856602
TI  - Patient factors associated with glucagonlike peptide 1 receptor agonist use with
      and without insulin.
AB  - OBJECTIVE: To evaluate both the patient factors associated with the initiation of
      exenatide and the real-world treatment patterns of exenatide use with and without
      insulin. METHODS: Using retrospective electronic medical records from the General
      Electric Centricity database, we performed analyses of 2 cohorts to separately
      evaluate factors associated with initiation of exenatide among patients with type
      2 diabetes mellitus and differences between those who initiated exenatide with
      and without concurrent insulin use. Cohort 1 was used to assess predictors of
      exenatide initiation and included adults with type 2 diabetes who were active in
      the database when exenatide became available (October 1, 2005). Cohort 2 was used
      to identify characteristics of patients who initiated exenatide with and without
      insulin. RESULTS: Cohort 1 included 190 444 adults, and cohort 2 included 9810
      adults. In cohort 1, 7383 patients initiated exenatide therapy; factors
      associated with exenatide initiation were female sex, younger age, body weight of
      102.3 kg or greater, body mass index of 35 kg/m2 or greater, residence in the
      southern United States, a lower Charlson Comorbidity Index, previous or existing
      therapy with triple oral antidiabetic drugs, and insulin plus oral antidiabetic
      drugs. In cohort 2, 2470 exenatide-treated patients initiated exenatide with
      insulin (25%) (with or without oral antidiabetic drugs). They were more likely to
      weigh more than 113.6 kg, have a body mass index greater than 40 kg/m2, have a
      Charlson Comorbidity Index of 2 or greater, and have a baseline hemoglobin A1c
      level greater than 9%. CONCLUSIONS: Exenatide concomitant with insulin use (with
      or without oral antidiabetic drugs) was common, and was more likely to be
      prescribed in patients with morbid obesity, comorbid conditions, and poor
      glycemic control. Randomized controlled trials are needed to confirm the safe and
      effective use of this combination.

PMID- 21856603
TI  - Qualitative research methods in mental health.
AB  - As the evidence base for the study of mental health problems develops, there is a
      need for increasingly rigorous and systematic research methodologies. Complex
      questions require complex methodological approaches. Recognising this, the MRC
      guidelines for developing and testing complex interventions place qualitative
      methods as integral to each stage of intervention development and implementation.
      However, mental health research has lagged behind many other healthcare
      specialities in using qualitative methods within its evidence base. Rigour in
      qualitative research raises many similar issues to quantitative research and also
      some additional challenges. This article examines the role of qualitative methods
      within mental heath research, describes key methodological and analytical
      approaches and offers guidance on how to differentiate between poor and good
      quality qualitative research.

PMID- 21856601
TI  - Changes in steroid concentrations with the timing of corticotropin stimulation
      testing in participants with adrenal sufficiency.
AB  - OBJECTIVE: To determine whether the time of day at which corticotropin
      stimulation testing is performed influences the steroid concentrations observed
      in persons with normal adrenal function. METHODS: In this retrospective,
      secondary analysis, participants with normal adrenal function were studied to
      determine whether the time of corticotropin stimulation testing influenced
      results. Participants consisted of 2 groups: healthy volunteers who were not
      suspected of having adrenal insufficiency and patients being tested for adrenal
      insufficiency as part of their standard of care who were subsequently shown to
      have normal adrenal function on the basis of a peak cortisol value of at least 20
      MUg/dL. A high-dose corticotropin stimulation test was performed in all
      participants. Baseline, peak, and delta steroid concentrations were documented
      after corticotropin injection. Steroid concentrations were measured by tandem
      mass spectrometry. Multivariate analyses adjusted for patient age, sex, and
      baseline steroid concentrations. RESULTS: With progression through the day for
      the time of testing, the baseline cortisol concentration decreased, while the
      peak and delta cortisol concentration increased (P values: <.001, .007, .007,
      respectively). For 11-deoxycortisol, the baseline decreased, while peak and delta
      values increased with later testing (P values: .017, .012, .02, respectively).
      Peak aldosterone concentrations increased according to their baseline values
      (P<.001), but were unaffected by time. Peak and delta dehydroepiandrosterone
      concentrations increased with time (P = .015 and .021, respectively). Referring
      to the various criteria for adequate steroid responses to corticotropin available
      in the literature, the time-related differences in this small group of patients
      were insufficient to draw different conclusions about results of testing.
      CONCLUSIONS: Cortisol, 11-deoxycortisol, and dehydroepiandrosterone values were
      most influenced by testing times. In patients with borderline adrenal function
      who are tested at different times of the day, the modest differences we observed
      may be sufficient to affect conclusions about whether adrenal insufficiency is
      present.

PMID- 21856604
TI  - Review: depression is associated with increased cancer mortality.

PMID- 21856605
TI  - Girls with ADHD have an increased risk of psychopathology in young adulthood.

PMID- 21856606
TI  - Recurrence of bipolar spectrum disorders--a common issue among the affected
      population of young people.

PMID- 21856607
TI  - Anticholinergic drugs increase the risk of cognitive decline and dementia in
      older people.

PMID- 21856608
TI  - Depressive symptoms highly prevalent after a musculoskeletal workplace injury.

PMID- 21856609
TI  - No differences in mortality and suicide between treated and never-treated people
      with schizophrenia.

PMID- 21856611
TI  - Interpersonal therapy or guided self-help CBT improve remission from binge eating
      compared to a behavioural weight-loss programme at 2-year post-treatment.

PMID- 21856610
TI  - Failure to improve during first 6 months of treatment and depression severity
      predict increased mortality in people with ACS and MDD.

PMID- 21856612
TI  - Review: benefits of antidepressants over placebo limited except in very severe
      depression.

PMID- 21856613
TI  - Online cognitive behavioural therapy is effective for depression in primary care.

PMID- 21856614
TI  - Review: is aripiprazole as effective as risperidone in people with schizophrenia?

PMID- 21856615
TI  - Review: antidepressants associated with increased risk of suicidality in adults
      aged less than 25 years.

PMID- 21856616
TI  - Review: ziprasidone is marginally less effective than other atypical
      antipsychotics in people with schizophrenia.

PMID- 21856617
TI  - Review: most antipsychotic drugs more than double the prolactin levels in
      children and adolescents.

PMID- 21856618
TI  - Review: there is no evidence that psychosocial interventions prevent disability
      after traumatic physical injury.

PMID- 21856619
TI  - Review: lack of evidence for the optimal dose of risperidone for schizophrenia.

PMID- 21856620
TI  - Estimates of how many cannabis users need to be prevented in order to prevent one
      case of schizophrenia.

PMID- 21856621
TI  - Increased risk of septal heart defects in newborns as a result of sertraline and
      citalopram intake during pregnancy.

PMID- 21856622
TI  - Frequent childhood victimisation predicts later psychiatric problems in females.

PMID- 21856623
TI  - Antipsychotic treatment associated with higher risk of hyperglycaemia in older
      persons with diabetes.

PMID- 21856624
TI  - Increase in proportion of patients on long-term medication accounts for increase
      in antidepressant prescribing in UK.

PMID- 21856625
TI  - Increased antidepressant and antipsychotic use in the USA between 1996 and 2005.

PMID- 21856626
TI  - HIV-positive young people at high risk of psychiatric disorders.

PMID- 21856627
TI  - Limited evidence that antipsychotic drug treatment is associated with reduced
      brain volume.

PMID- 21856628
TI  - Biogeography revisited with network theory: retracing the history of hydrothermal
      vent communities.
AB  - Defining biogeographic provinces to understand the history and evolution of
      communities associated with a given kind of ecosystem is challenging and usually
      requires a priori assumptions to be made. We applied network theory, a holistic
      and exploratory method, to the most complete database of faunal distribution
      available on oceanic hydrothermal vents, environments which support fragmented
      and unstable ecosystems, to infer the processes driving their worldwide
      biogeography. Besides the identification of robust provinces, the network
      topology allowed us to identify preferential pathways that had hitherto been
      overlooked. These pathways are consistent with the previously proposed hypothesis
      of a role of plate tectonics in the biogeographical history of hydrothermal vent
      communities. A possible ancestral position of the Western Pacific is also
      suggested for the first time. Finally, this work provides an innovative example
      of the potential of network tools to unravel the biogeographic history of faunal
      assemblages and to supply comprehensive information for the conservation and
      management of biodiversity.

PMID- 21856629
TI  - Correlating early evolution of parasitic platyhelminths to Gondwana breakup.
AB  - Investigating patterns and processes of parasite diversification over ancient
      geological periods should involve comparisons of host and parasite phylogenies in
      a biogeographic context. It has been shown previously that the geographical
      distribution of host-specific parasites of sarcopterygians was guided, from
      Palaeozoic to Cainozoic times, mostly by evolution and diversification of their
      freshwater hosts. Here, we propose phylogenies of neobatrachian frogs and their
      specific parasites (Platyhelminthes, Monogenea) to investigate coevolutionary
      processes and historical biogeography of polystomes and further discuss all the
      possible assumptions that may account for the early evolution of these parasites.
      Phylogenetic analyses of concatenated rRNA nuclear genes (18S and partial 28S)
      supplemented by cophylogenetic and biogeographic vicariance analyses reveal four
      main parasite lineages that can be ascribed to centers of diversity, namely
      Australia, India, Africa, and South America. In addition, the relationships among
      these biogeographical monophyletic groups, substantiated by molecular dating,
      reflect sequential origins during the breakup of Gondwana. The Australian
      polystome lineage may have been isolated during the first stages of the breakup,
      whereas the Indian lineage would have arisen after the complete separation of
      western and eastern Gondwanan components. Next, polystomes would have codiverged
      with hyloid sensu stricto and ranoid frog lineages before the completion of South
      American and African plate separation. Ultimately, they would have undergone an
      extensive diversification in South America when their ancestral host families
      diversified. Therefore, the presence of polystome parasites in specific anuran
      host clades and in discrete geographic areas reveals the importance of
      biogeographic vicariance in diversification processes and supports the occurrence
      and radiation of amphibians over ancient and recent geological periods.

PMID- 21856630
TI  - Predicting total global species richness using rates of species description and
      estimates of taxonomic effort.
AB  - We found that trends in the rate of description of 580,000 marine and terrestrial
      species, in the taxonomically authoritative World Register of Marine Species and
      Catalogue of Life databases, were similar until the 1950s. Since then, the
      relative number of marine to terrestrial species described per year has
      increased, reflecting the less explored nature of the oceans. From the mid-19th
      century, the cumulative number of species described has been linear, with the
      highest number of species described in the decade of 1900, and fewer species
      described and fewer authors active during the World Wars. There were more authors
      describing species since the 1960s, indicating greater taxonomic effort. There
      were fewer species described per author since the 1920s, suggesting it has become
      more difficult to discover new species. There was no evidence of any change in
      individual effort by taxonomists. Using a nonhomogeneous renewal process model we
      predicted that 24-31% to 21-29% more marine and terrestrial species remain to be
      discovered, respectively. We discuss why we consider that marine species comprise
      only 16% of all species on Earth although the oceans contain a greater
      phylogenetic diversity than occurs on land. We predict that there may be 1.8-2.0
      million species on Earth, of which about 0.3 million are marine, significantly
      less than some previous estimates.

PMID- 21856631
TI  - Calibrated tree priors for relaxed phylogenetics and divergence time estimation.
AB  - The use of fossil evidence to calibrate divergence time estimation has a long
      history. More recently, Bayesian Markov chain Monte Carlo has become the dominant
      method of divergence time estimation, and fossil evidence has been reinterpreted
      as the specification of prior distributions on the divergence times of
      calibration nodes. These so-called "soft calibrations" have become widely used
      but the statistical properties of calibrated tree priors in a Bayesian setting
      hashave not been carefully investigated. Here, we clarify that calibration
      densities, such as those defined in BEAST 1.5, do not represent the marginal
      prior distribution of the calibration node. We illustrate this with a number of
      analytical results on small trees. We also describe an alternative construction
      for a calibrated Yule prior on trees that allows direct specification of the
      marginal prior distribution of the calibrated divergence time, with or without
      the restriction of monophyly. This method requires the computation of the Yule
      prior conditional on the height of the divergence being calibrated.
      Unfortunately, a practical solution for multiple calibrations remains elusive.
      Our results suggest that direct estimation of the prior induced by specifying
      multiple calibration densities should be a prerequisite of any divergence time
      dating analysis.

PMID- 21856632
TI  - Molecular mechanisms controlling legume autoregulation of nodulation.
AB  - BACKGROUND: High input costs and environmental pressures to reduce nitrogen use
      in agriculture have increased the competitive advantage of legume crops. The
      symbiotic relationship that legumes form with nitrogen-fixing soil bacteria in
      root nodules is central to this advantage. SCOPE: Understanding how legume plants
      maintain control of nodulation to balance the nitrogen gains with their energy
      needs and developmental costs will assist in increasing their productivity and
      relative advantage. For this reason, the regulation of nodulation has been
      extensively studied since the first mutants exhibiting increased nodulation were
      isolated almost three decades ago. CONCLUSIONS: Nodulation is regulated primarily
      via a systemic mechanism known as the autoregulation of nodulation (AON), which
      is controlled by a CLAVATA1-like receptor kinase. Multiple components sharing
      homology with the CLAVATA signalling pathway that maintains control of the shoot
      apical meristem in arabidopsis have now been identified in AON. This includes the
      recent identification of several CLE peptides capable of activating nodule
      inhibition responses, a low molecular weight shoot signal and a role for CLAVATA2
      in AON. Efforts are now being focused on directly identifying the interactions of
      these components and to identify the form that long-distance transport molecules
      take.

PMID- 21856633
TI  - Low but structured chloroplast diversity in Atherosperma moschatum
      (Atherospermataceae) suggests bottlenecks in response to the Pleistocene
      glacials.
AB  - BACKGROUND AND AIMS: The cool temperate rainforests of Australia were much
      reduced in range during the cold and dry glacial periods, although genetic
      evidence indicates that two key rainforest species, Nothofagus cunninghamii and
      Tasmannia lanceolata, survived within multiple locations and underwent only local
      range expansions at the end of the Last Glacial. To better understand the glacial
      response of a co-occurring but wind-dispersed and less cold-tolerant rainforest
      tree species, Atherosperma moschatum, a chloroplast phylogeographic study was
      undertaken. METHODS: A total of 3294 bp of chloroplast DNA sequence was obtained
      for 155 samples collected from across the species' range. KEY RESULTS: The
      distribution of six haplotypes observed in A. moschatum was geographically
      structured with an inferred ancestral haplotype restricted to Tasmania, while
      three non-overlapping and endemic haplotypes were found on the mainland of south
      eastern Australia. Last glacial refugia for A. moschatum are likely to have
      occurred in at least one location in western Tasmania and in Victoria and within
      at least two locations in the Great Dividing Range of New South Wales. Nucleotide
      diversity of A. moschatum was lower (pi = 0.00021) than either N. cunninghamii
      (0.00101) or T. lanceolata (0.00073), and was amongst the lowest recorded for any
      tree species. CONCLUSIONS: This study provides evidence for past bottlenecks
      having impacted the chloroplast diversity of A. moschatum as a result of the
      species narrower climatic niche during glacials. This hypothesis is supported by
      the star-like haplotype network and similar estimated rates of chloroplast DNA
      substitution for A. moschatum and the two more cold tolerant and co-occurring
      species that have higher chloroplast diversity, N. cunninghamii and T.
      lanceolata.

PMID- 21856634
TI  - Towards a functional-structural plant model of cut-rose: simulation of light
      environment, light absorption, photosynthesis and interference with the plant
      structure.
AB  - BACKGROUND AND AIMS: The production system of cut-rose (Rosa * hybrida) involves
      a complex combination of plant material, management practice and environment.
      Plant structure is determined by bud break and shoot development while having an
      effect on local light climate. The aim of the present study is to cover selected
      aspects of the cut-rose system using functional-structural plant modelling
      (FSPM), in order to better understand processes contributing to produce quality
      and quantity. METHODS: The model describes the production system in three
      dimensions, including a virtual greenhouse environment with the crop, light
      sources (diffuse and direct sun light and lamps) and photosynthetically active
      radiation (PAR) sensors. The crop model is designed as a multiscaled FSPM with
      plant organs (axillary buds, leaves, internodes, flowers) as basic units, and
      local light interception and photosynthesis within each leaf. A Monte-Carlo light
      model was used to compute the local light climate for leaf photosynthesis, the
      latter described using a biochemical rate model. KEY RESULTS: The model was able
      to reproduce PAR measurements taken at different canopy positions, different
      times of the day and different light regimes. Simulated incident and absorbed PAR
      as well as net assimilation rate in upright and bent shoots showed characteristic
      spatial and diurnal dynamics for different common cultivation scenarios.
      CONCLUSIONS: The model of cut-rose presented allowed the creation of a range of
      initial structures thanks to interactive rules for pruning, cutting and bending.
      These static structures can be regarded as departure points for the dynamic
      simulation of production of flower canes. Furthermore, the model was able to
      predict local (per leaf) light absorption and photosynthesis. It can be used to
      investigate the physiology of ornamental plants, and provide support for the
      decisions of growers and consultants.

PMID- 21856635
TI  - Comparative labellar micromorphology of Zygopetalinae (Orchidaceae).
AB  - BACKGROUND AND AIMS: Molecular evidence indicates that the Neotropical sub-tribe
      Zygopetalinae is sister to Maxillariinae. Most members of the latter sub-tribe
      have deceit pollination strategies, but some species produce rewards such as
      nectar, pseudopollen, resin and wax, and are pollinated by a range of pollinators
      that include stingless bees (Meliponini), wasps and hummingbirds. By contrast,
      relatively little is known about the pollination of Zygopetalinae species.
      However, some are pollinated by fragrance-gathering, male euglossine bees or
      employ nectar deceit strategies. The aim of this study is to describe the
      labellar micromorphology of Zygopetalinae and to compare it with that of
      Maxillariinae sensu lato (s.l.) as part of an ongoing project to record the range
      of labellar characters found within the tribe Maxillarieae, and to assess whether
      these characters represent synapomorphies or homoplasies resulting from similar
      pollination pressures. METHODS: The labella of 31 species of Zygopetalinae,
      including Cryptarrhena R. Br. and representatives of the Zygopetalum, Huntleya
      and Warrea clades, were examined using light microscopy and scanning electron
      microscopy, and the range of labellar characters was recorded. These characters
      were subsequently compared with those of Maxillariinae s.l. which formed the
      subject of our previous investigations. KEY RESULTS AND CONCLUSIONS: The labellar
      micromorphology of Zygopetalinae is less diverse than that of Maxillariinae and
      does not reflect the currently accepted phylogeny of the former sub-tribe based
      on molecular studies. Instead, the relative uniformity in labellar
      micromorphology of Zygopetalinae is probably due to homoplasies resulting from
      similar pollinator pressures. Labellar trichomes are relatively uncommon in
      Zygopetalinae, but occur in certain members of both the Zygopetalum and Huntleya
      clades. Trichomes are unbranched, uniseriate and multicellular with rounded
      apices, or unbranched and unicellular, with tapering, pointed and flexuose
      apices. Hitherto, unicellular trichomes of this kind have been observed only for
      euglossophilous orchid taxa, and the adoption of a relatively limited range of
      pollination strategies by Zygopetalinae may have resulted in reduced investment
      in micromorphological labellar characters.

PMID- 21856636
TI  - Mass extinction, gradual cooling, or rapid radiation? Reconstructing the
      spatiotemporal evolution of the ancient angiosperm genus Hedyosmum
      (Chloranthaceae) using empirical and simulated approaches.
AB  - Chloranthaceae is a small family of flowering plants (65 species) with an
      extensive fossil record extending back to the Early Cretaceous. Within
      Chloranthaceae, Hedyosmum is remarkable because of its disjunct distribution--1
      species in the Paleotropics and 44 confined to the Neotropics--and a long
      "temporal gap" between its stem age (Early Cretaceous) and the beginning of the
      extant radiation (late Cenozoic). Is this gap real, reflecting low
      diversification and a recent radiation, or the signature of extinction? Here we
      use paleontological data, relaxed-clock molecular dating, diversification
      analyses, and parametric ancestral area reconstruction to investigate the timing,
      tempo, and mode of diversification in Hedyosmum. Our results, based on analyses
      of plastid and nuclear sequences for 40 species, suggest that the ancestor of
      Chloranthaceae and the Hedyosmum stem lineages were widespread in the Holarctic
      in the Late Cretaceous. High extinction rates, possibly associated with Cenozoic
      climatic fluctuations, may have been responsible for the low extant diversity of
      the family. Crown group Hedyosmum originated c. 36-43 Ma and colonized South
      America from the north during the Early-Middle Miocene (c. 20 Ma). This coincided
      with an increase in diversification rates, probably triggered by the uplift of
      the Northern Andes from the Mid-Miocene onward. This study illustrates the
      advantages of combining paleontological, phylogenetic, and biogeographic data to
      reconstruct the spatiotemporal evolution of an ancient lineage, for which the
      extant diversity is only a remnant of past radiations. It also shows the
      difficulties of inferring patterns of lineage diversification when incomplete
      taxon sampling is combined with high extinction rates.

PMID- 21856637
TI  - Ontogeny, understorey light interception and simulated carbon gain of juvenile
      rainforest evergreens differing in shade tolerance.
AB  - BACKGROUND AND AIMS: A long-running debate centres on whether shade tolerance of
      tree seedlings is mainly a function of traits maximizing net carbon gain in low
      light, or of traits minimizing carbon loss. To test these alternatives, leaf
      display, light-interception efficiency, and simulated net daily carbon gain of
      juvenile temperate evergreens of differing shade tolerance were measured, and how
      these variables are influenced by ontogeny was queried. METHODS: The biomass
      distribution of juveniles (17-740 mm tall) of seven temperate rainforest
      evergreens growing in low (approx. 4 %) light in the understorey of a second
      growth stand was quantified. Daytime and night-time gas exchange rates of leaves
      were also determined, and crown architecture was recorded digitally. YPLANT was
      used to model light interception and carbon gain. RESULTS: An index of species
      shade tolerance correlated closely with photosynthetic capacities and respiration
      rates per unit mass of leaves, but only weakly with respiration per unit area.
      Accumulation of many leaf cohorts by shade-tolerant species meant that their
      ratios of foliage area to biomass (LAR) decreased more gradually with ontogeny
      than those of light-demanders, but also increased self-shading; this depressed
      the foliage silhouette-to-area ratio (STAR), which was used as an index of light
      interception efficiency. As a result, displayed leaf area ratio (LAR(d) = LAR *
      STAR) of large seedlings was not related to species shade tolerance. Self-shading
      also caused simulated net daily carbon assimilation rates of shade-tolerant
      species to decrease with ontogeny, leading to a negative correlation of shade
      tolerance with net daily carbon gain of large (500 mm tall) seedlings in the
      understorey. CONCLUSIONS: The results suggest that efficiency of energy capture
      is not an important correlate of shade tolerance in temperate rainforest
      evergreens. Ontogenetic increases in self-shading largely nullify the potential
      carbon gain advantages expected to result from low respiration rates and long
      leaf lifespans in shade-tolerant evergreens. The main advantage of their long
      lived leaves is probably in reducing the costs of crown maintenance.

PMID- 21856638
TI  - Involvement of nitric oxide and auxin in signal transduction of copper-induced
      morphological responses in Arabidopsis seedlings.
AB  - BACKGROUND AND AIMS: Plants are able to adapt to the environment dynamically
      through regulation of their growth and development. Excess copper (Cu(2+)), a
      toxic heavy metal, induces morphological alterations in plant organs; however,
      the underlying mechanisms are still unclear. With this in mind, the multiple
      signalling functions of nitric oxide (NO) in plant cells and its possible
      regulatory role and relationship with auxin were examined during Cu(2+)-induced
      morphological responses. METHODS: Endogenous auxin distribution was determined by
      microscopic observation of X-Gluc-stained DR5::GUS arabidopsis, and the levels of
      NO, superoxide and peroxynitrite were detected by fluorescence microscopy. As
      well as wild-type, NO-overproducer (nox1) and -deficient (nia1nia2 and
      nia1nia2noa1-2) arabidopsis plants were used. KEY RESULTS: Cu(2+) at a
      concentration of 50 um resulted in a large reduction in cotyledon area and
      hypocotyl and primary root lengths, accompanied by an increase in auxin levels.
      In cotyledons, a low Cu(2+) concentration promoted NO accumulation, which was
      arrested by nitric oxide synthase or nitrate reductase inhibitors. The 5-MUm
      Cu(2+)-induced NO synthesis was not detectable in nia1nia2 or nia1nia2noa1-2
      plants. In roots, Cu(2+) caused a decrease of the NO level which was not
      associated with superoxide and peroxynitrite formation. Inhibition of auxin
      transport resulted in an increase in NO levels, while exogenous application of an
      NO donor reduced DR5::GUS expression. The elongation processes of nox1 were not
      sensitive to Cu(2+), but NO-deficient plants showed diverse growth responses.
      CONCLUSIONS: In plant organs, Cu(2+) excess results in severe morphological
      responses during which the endogenous hormonal balance and signal transduction
      are affected. Auxin and NO negatively regulate each other's level and NO
      intensifies the metal-induced cotyledon expansion, but mitigates elongation
      processes under Cu(2+) exposure.

PMID- 21856640
TI  - Physicians' calling patients on excess weight may provide reality check and
      increase desire to lose weight in overweight and obese individuals.

PMID- 21856639
TI  - Fruit regulates seasonal expression of flowering genes in alternate-bearing
      'Moncada' mandarin.
AB  - BACKGROUND AND AIMS: The presence of fruit has been widely reported to act as an
      inhibitor of flowering in fruit trees. This study is an investigation into the
      effect of fruit load on flowering of 'Moncada' mandarin and on the expression of
      putative orthologues of genes involved in flowering pathways to provide insight
      into the molecular mechanisms underlying alternate bearing in citrus. METHODS:
      The relationship between fruit load and flowering intensity was examined first.
      Defruiting experiments were further conducted to demonstrate the causal effect of
      fruit removal upon flowering. Finally, the activity of flowering-related genes
      was investigated to determine the extent to which their seasonal expression is
      affected by fruit yield. KEY RESULTS: First observations and defruiting
      experiments indicated a significant inverse relationship between preceding fruit
      load and flowering intensity. Moreover, data indicated that when fruit remained
      on the tree from November onwards, a dramatic inhibition of flowering occurred
      the following spring. The study of the expression pattern of flowering-genes of
      on (fully loaded) and off (without fruits) trees revealed that homologues of
      FLOWERING LOCUS T (FT), SUPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1),
      APETALA1 (AP1) and LEAFY (LFY) were negatively affected by fruit load. Thus, CiFT
      expression showed a progressive increase in leaves from off trees through the
      study period, the highest differences found from December onwards (10-fold).
      Whereas differences in the relative expression of SOC1 only reached significance
      from September to mid-December, CsAP1 expression was constantly higher in those
      trees through the whole study period. Significant variations in CsLFY expression
      only were found in late February (close to 20 %). On the other hand, the
      expression of the homologues of TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS C
      (FLC) did not appear to be related to fruit load. CONCLUSIONS: These results
      suggest for the first time that fruit inhibits flowering by repressing CiFT and
      SOC1 expression in leaves of alternate-bearing citrus. Fruit also reduces CsAP1
      expression in leaves, and the significant increase in leaf CsLFY expression from
      off trees in late February was associated with the onset of floral
      differentiation.

PMID- 21856641
TI  - Initial treatment of hypertension with aliskiren and amlodipine combination gives
      6.5 mm Hg greater reduction in systolic BP than does either monotherapy.

PMID- 21856642
TI  - Systematic review of observational studies finds increased risk of fracture among
      older adults taking a proton pump inhibitor.

PMID- 21856643
TI  - Getting sports injury prevention on to public health agendas - addressing the
      shortfalls in current information sources.
AB  - Public health policy is a successful population-level strategy for injury
      prevention but it is yet to be widely applied to the sports sector. Such policy
      is generally coordinated by government health departments concerned with the
      allocation of limited resources to health service delivery and preventive
      programs for addressing large community health issues. Prioritisation of sports
      injury prevention (SIP) requires high-quality evidence about the size of the
      problem and its public health burden; identification of at-risk vulnerable
      groups; confirmed effective prevention solutions; evidence of intervention cost
      effectiveness; and quantification of both financial and policy implications of
      inaction. This paper argues that the major reason for a lack of sports injury
      policy by government departments for health or sport to date is a lack of
      relevant information available for policy makers to make their decisions. Key
      information gaps evident in Australia are used to highlight this problem. SIP
      policy does not yet rank highly because, relative to other health/injury issues,
      there is very little hard evidence to support: claims for its priority ranking,
      the existence of solutions that can be implemented and which will work, and
      potential cost-savings to government agencies. Moreover, policy action needs to
      be integrated across government portfolios, including sport, health and others.
      Until sports medicine research generates high-quality population-level
      information of direct relevance and importance to policy makers, especially
      intervention costing and implementation cost-benefit estimates, and fully engage
      in policy-informing partnerships, SIP will continue to be left off the public
      health agenda.

PMID- 21856644
TI  - Enteral feeding practices in very preterm infants: an international survey.
AB  - OBJECTIVE: To evaluate enteral feeding practices in neonatal units in different
      countries and on different continents. DESIGN: A web-based survey of 127 tertiary
      neonatal intensive care units in Australia, Canada, Denmark, Ireland, New
      Zealand, Norway, Sweden and the UK. RESULTS: 124 units (98%) responded. 59 units
      (48%) had a breast milk bank or access to donor human milk (Australia/New Zealand
      2/27, Canada 6/29, Scandinavia 20/20 and UK/Ireland 31/48). The proportion of
      units initiating enteral feeding within the first 24 h of life was: 43/124 (35%)
      if gestational age (GA) <25 weeks, 53/124 (43%) if GA 25-27 weeks and 88/124
      (71%) if GA 28-31 weeks. In general, Scandinavian units introduced enteral feeds
      the earliest, followed by UK/Ireland. Continuous feeding was routinely used for
      infants below 28 weeks' gestation in almost half of the Scandinavian units and in
      approximately one sixth of units in UK/Ireland, but rarely in Australia/New
      Zealand and Canada. Minimal enteral feeding for 4-5 days was common in Canada,
      but rare in Scandinavia. Target enteral feeding volume in a 'stable' preterm
      infant was 140-160 ml/kg/day in most Canadian units and 161-180 ml/kg/day or
      higher in units in the other regions. There were also marked regional differences
      in criteria for use and timing when human milk fortifier was added. CONCLUSIONS:
      This study highlights areas of uncertainty and demonstrates marked variability in
      feeding practices. It provides valuable data for planning collaborative feeding
      trials to optimise outcome in preterm infants.

PMID- 21856645
TI  - The Arabidopsis sn-1-specific mitochondrial acylhydrolase AtDLAH is positively
      correlated with seed viability.
AB  - Lipid-derived molecules produced by acylhydrolases play important roles in the
      regulation of diverse cellular functions in plants. In Arabidopsis, the DAD1-like
      phospholipase A1 family consists of 12 members, all of which possess a lipase 3
      domain. In this study, the biochemical and cellular functions of AtDLAH, an
      Arabidopsis thaliana DAD1-like acylhydrolase, were examined. Bacterially
      expressed AtDLAH contained phospholipase A1 activity for catalysing the
      hydrolysis of phospholipids at the sn-1 position. However, AtDLAH displayed an
      even stronger preference for 1-lysophosphatidylcholine, 1-monodiacylglycerol, and
      phosphatidic acid, suggesting that AtDLAH is a sn-1-specific acylhydrolase. The
      AtDLAH gene was highly expressed in young seedlings, and its encoded protein was
      exclusively localized to the mitochondria. AtDLAH-overexpressing transgenic seeds
      (35S:AtDLAH) were markedly tolerant to accelerated-ageing treatment and thus had
      higher germination percentages than wild-type seeds. In contrast, the atdlah loss
      of-function knockout mutant seeds were hypersusceptible to accelerated-ageing
      conditions. The 35S:AtDLAH seeds, as opposed to the atdlah seeds, exhibited a
      dark red staining pattern following tetrazolium treatment under both normal and
      accelerated-ageing conditions, suggesting that AtDLAH expression is positively
      correlated with seed viability. The enhanced viability of 35S:AtDLAH seeds was
      accompanied by more densely populated epidermal cells, lower levels of
      accumulated lipid hydroperoxides, and higher levels of polar lipids as compared
      with wild-type and atdlah mutant seeds. These results suggest that AtDLAH, a
      mitochondrial-localized sn-1-specific acylhydrolase, plays an important role in
      Arabidopsis seed viability.

PMID- 21856646
TI  - Diglycolic acid is the nephrotoxic metabolite in diethylene glycol poisoning
      inducing necrosis in human proximal tubule cells in vitro.
AB  - Diethylene glycol (DEG), a solvent and chemical intermediate, can produce an
      acute toxic syndrome, the hallmark of which is acute renal failure due to
      cortical tubular degeneration and proximal tubular necrosis. DEG is metabolized
      to two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic
      acid (DGA), which are believed to be the proximate toxicants. The precise
      mechanism of toxicity has yet to be elucidated, so these studies were designed to
      determine which metabolite was responsible for the proximal tubule cell death.
      Human proximal tubule (HPT) cells in culture, obtained from normal cortical
      tissue and passaged 3-6 times, were incubated with increasing concentrations of
      DEG, 2-HEAA, or DGA separately and in combination for 48 h at pH 6 or 7.4, and
      various parameters of necrotic and apoptotic cell death were measured. DEG and 2
      HEAA did not produce any cell death. DGA produced dose-dependent necrosis at
      concentrations above 25 mmol/l. DGA did not affect caspase-3 activity and
      increased annexin V staining only in propidium iodide-stained cells. Hence, DGA
      induced necrosis, not apoptosis, as corroborated by severe depletion of cellular
      adenosine triphosphate levels. DGA is structurally similar to citric acid cycle
      intermediates that are taken up by specific transporters in kidney cells. HPT
      cells, incubated with N-(p-amylcinnamoyl)anthranilic acid, a sodium dicarboxylate
      1 transporter inhibitor showed significantly decreased cell death compared with
      DGA alone. These studies demonstrate that DGA is the toxic metabolite responsible
      for DEG-induced proximal tubular necrosis and suggest a possible transporter
      mediated uptake of DGA leading to toxic accumulation and cellular dysfunction.

PMID- 21856647
TI  - Reduced efficacy of natural selection on codon usage bias in selfing Arabidopsis
      and Capsella species.
AB  - Population genetic theory predicts that the efficacy of natural selection in a
      self-fertilizing species should be lower than its outcrossing relatives because
      of the reduction in the effective population size (N(e)) in the former brought
      about by inbreeding. However, previous analyses comparing Arabidopsis thaliana
      (selfer) with A. lyrata (outcrosser) have not found conclusive support for this
      prediction. In this study, we addressed this issue by examining silent site
      polymorphisms (synonymous and intronic), which are expected to be informative
      about changes in N(e). Two comparisons were made: A. thaliana versus A. lyrata
      and Capsella rubella (selfer) versus C. grandiflora (outcrosser). Extensive
      polymorphism data sets were obtained by compiling published data from the
      literature and by sequencing 354 exon loci in C. rubella and 89 additional loci
      in C. grandiflora. To extract information from the data effectively for studying
      these questions, we extended two recently developed models in order to
      investigate detailed selective differences between synonymous codons, mutational
      biases, and biased gene conversion (BGC), taking into account the effects of
      recent changes in population size. We found evidence that selection on synonymous
      codons is significantly weaker in the selfers compared with the outcrossers and
      that this difference cannot be fully accounted for by mutational biases or BGC.

PMID- 21856650
TI  - A robust method using propensity score stratification for correcting verification
      bias for binary tests.
AB  - Sensitivity and specificity are common measures of the accuracy of a diagnostic
      test. The usual estimators of these quantities are unbiased if data on the
      diagnostic test result and the true disease status are obtained from all subjects
      in an appropriately selected sample. In some studies, verification of the true
      disease status is performed only for a subset of subjects, possibly depending on
      the result of the diagnostic test and other characteristics of the subjects.
      Estimators of sensitivity and specificity based on this subset of subjects are
      typically biased; this is known as verification bias. Methods have been proposed
      to correct verification bias under the assumption that the missing data on
      disease status are missing at random (MAR), that is, the probability of
      missingness depends on the true (missing) disease status only through the test
      result and observed covariate information. When some of the covariates are
      continuous, or the number of covariates is relatively large, the existing methods
      require parametric models for the probability of disease or the probability of
      verification (given the test result and covariates), and hence are subject to
      model misspecification. We propose a new method for correcting verification bias
      based on the propensity score, defined as the predicted probability of
      verification given the test result and observed covariates. This is estimated
      separately for those with positive and negative test results. The new method
      classifies the verified sample into several subsamples that have homogeneous
      propensity scores and allows correction for verification bias. Simulation studies
      demonstrate that the new estimators are more robust to model misspecification
      than existing methods, but still perform well when the models for the probability
      of disease and probability of verification are correctly specified.

PMID- 21856649
TI  - Racial and ethnic differences in all-cause mortality risk according to alcohol
      consumption patterns in the national alcohol surveys.
AB  - Previous studies have found J-shaped relations between volume of alcohol consumed
      and mortality risk in white Americans but not in African Americans, suggesting
      the need for studies in which race/ethnicity-defined subgroups are analyzed in
      separate comparable models. In the present study, the authors utilized mortality
      follow-up data (through 2006) on respondents from the 1984 and 1995 National
      Alcohol Surveys, including similar numbers of black, white, and Hispanic
      respondents by oversampling the minority groups. Cox proportional hazards models
      controlling for demographic, socioeconomic, mental health, and drug- and tobacco
      use measures were used to estimate mortality risk from all causes. Findings
      indicated a protective effect of moderate alcohol drinking (2-30 drinks/month for
      women and 2-60 drinks/month for men) with no monthly >=5-drink days) relative to
      lifetime abstention for whites only. Elevated mortality risk relative to moderate
      drinking was found in former drinkers with lifetime alcohol problems. Moderate
      drinkers who consumed >=5 drinks in 1 day at least monthly were also found to
      have increased risk, suggesting the importance of identifying heavy-occasion
      drinking for mortality analyses. These differential results regarding lifetime
      abstainers may suggest bias from differential unmeasured confounding or
      unmeasured aspects of alcohol consumption pattern or may be due to genetic
      differences in the health impact of alcohol metabolism.

PMID- 21856651
TI  - A Bayesian hierarchical model for identifying epitopes in peptide microarray
      data.
AB  - Peptide Microarray Immunoassay (PMI for brevity) is a novel technology that
      enables researchers to map a large number of proteomic measurements at a peptide
      level, providing information regarding the relationship between antibody response
      and clinical sensitivity. PMI studies aim at recognizing antigen-specific
      antibodies from serum samples and at detecting epitope regions of the protein
      antigen. PMI data present new challenges for statistical analysis mainly due to
      the structural dependence among peptides. A PMI is made of a complete library of
      consecutive peptides. They are synthesized by systematically shifting a window of
      a fixed number of amino acids through the finite sequence of amino acids of the
      antigen protein as ordered in the primary structure of the protein. This implies
      that consecutive peptides have a certain number of amino acids in common and
      hence are structurally dependent. We propose a new flexible Bayesian hierarchical
      model framework, which allows one to detect recognized peptides and bound epitope
      regions in a single framework, taking into account the structural dependence
      between peptides through a suitable latent Markov structure. The proposed model
      is illustrated using PMI data from a recent study about egg allergy. A simulation
      study shows that the proposed model is more powerful and robust in terms of
      epitope detection than simpler models overlooking some of the dependence
      structure.

PMID- 21856648
TI  - Evolution of retinoid and steroid signaling: vertebrate diversification from an
      amphioxus perspective.
AB  - Although the physiological relevance of retinoids and steroids in vertebrates is
      very well established, the origin and evolution of the genetic machineries
      implicated in their metabolic pathways is still very poorly understood. We
      investigated the evolution of these genetic networks by conducting an exhaustive
      survey of components of the retinoid and steroid pathways in the genome of the
      invertebrate chordate amphioxus (Branchiostoma floridae). Due to its phylogenetic
      position at the base of chordates, amphioxus is a very useful model to identify
      and study chordate versus vertebrate innovations, both on a morphological and a
      genomic level. We have characterized more than 220 amphioxus genes evolutionarily
      related to vertebrate components of the retinoid and steroid pathways and found
      that, globally, amphioxus has orthologs of most of the vertebrate components of
      these two pathways, with some very important exceptions. For example, we failed
      to identify a vertebrate-like machinery for retinoid storage, transport, and
      delivery in amphioxus and were also unable to characterize components of the
      adrenal steroid pathway in this invertebrate chordate. The absence of these genes
      from the amphioxus genome suggests that both an elaboration and a refinement of
      the retinoid and steroid pathways took place at the base of the vertebrate
      lineage. In stark contrast, we also identified massive amplifications in some
      amphioxus gene families, most extensively in the short-chain
      dehydrogenase/reductase superfamily, which, based on phylogenetic and genomic
      linkage analyses, were likely the result of duplications specific to the
      amphioxus lineage. In sum, this detailed characterization of genes implicated in
      retinoid and steroid signaling in amphioxus allows us not only to reconstruct an
      outline of these pathways in the ancestral chordate but also to discuss
      functional innovations in retinoid homeostasis and steroid-dependent regulation
      in both cephalochordate and vertebrate evolution.

PMID- 21856652
TI  - Evaluating prognostic accuracy of biomarkers in nested case-control studies.
AB  - Nested case-control (NCC) design is used frequently in epidemiological studies as
      a cost-effective subcohort sampling strategy to conduct biomarker research.
      Sampling strategy, on the other hoand, creates challenges for data analysis
      because of outcome-dependent missingness in biomarker measurements. In this
      paper, we propose inverse probability weighted (IPW) methods for making inference
      about the prognostic accuracy of a novel biomarker for predicting future events
      with data from NCC studies. The consistency and asymptotic normality of these
      estimators are derived using the empirical process theory and convergence
      theorems for sequences of weakly dependent random variables. Simulation and
      analysis using Framingham Offspring Study data suggest that the proposed methods
      perform well in finite samples.

PMID- 21856653
TI  - Lungworm outbreaks in adult dairy cows: estimating economic losses and lessons to
      be learned.
AB  - Two lungworm outbreaks in dairy herds were investigated in order to estimate the
      resulting economic costs. On the two farms, with 110 and 95 cows, total costs
      were estimated at ?159 and ?167 per cow, respectively. Overall, milk production
      reduced by 15 to 20 per cent during the outbreaks. Five cows died on one farm,
      while on the other farm seven cows died as a result of the lungworm outbreak. On
      one farm, 51.7 per cent of the total costs was due to reduced milk production and
      33.1 per cent was due to disposal of dead animals. On the other farm, it was 36.3
      and 50.9 per cent, respectively. The remaining 13 to 15 per cent of the total
      costs were due to extra inseminations, laboratory diagnosis and treatments. The
      history and development of the outbreaks are described. One lesson from these
      outbreaks is that recognising that potentially lungworm-naive animals are to be
      introduced into the adult herd allows for timely measures (for example,
      vaccination) to prevent a lungworm outbreak.

PMID- 21856654
TI  - Transpiration modulates phosphorus acquisition in tropical tree seedlings.
AB  - Several experiments were conducted with tropical tree and liana seedlings in
      which transpiration ratio and leaf phosphorus to carbon ratio (P:C) were
      measured. Transpiration ratio was expressed as kg H(2)O transpired&emsp14;g(-1) C
      incorporated into plant biomass, and leaf P:C as mg P&emsp14;g(-1) C. Leaf P:C
      was positively correlated with transpiration ratio across 19 species for plants
      grown under similar conditions (R(2) = 0.35, P < 0.01, n = 19). For five species
      in the dataset, multiple treatments were imposed to cause intra-specific
      variation in transpiration ratio. Within four of these five species, leaf P:C
      correlated positively with transpiration ratio. The slope and strength of the
      correlation varied among species. In one experiment, whole-plant P:C was measured
      in addition to leaf P:C. Patterns of correlation between whole-plant P:C and
      transpiration ratio were similar to those between leaf P:C and transpiration
      ratio. Together, these observations suggest that transpiration can influence the
      rate of P uptake from soil in tropical tree and liana seedlings. We suggest that
      this occurs through transport of inorganic phosphate and organic P compounds to
      root surfaces by transpiration-induced mass flow of the soil solution. The
      positive correlation between leaf P:C and transpiration ratio suggests that leaf
      P:C could decline in tropical forests as atmospheric CO(2) concentration rises,
      due to decreasing transpiration ratios.

PMID- 21856655
TI  - Vertical profiles reveal impact of ozone and temperature on carbon assimilation
      of Betula pendula and Populus tremula.
AB  - Rising temperature and tropospheric ozone (O(3)) concentrations are likely to
      affect carbon assimilation processes and thus the carbon sink strength of trees.
      In this study, we investigated the joint action of elevated ozone and temperature
      on silver birch (Betula pendula) and European aspen (Populus tremula) saplings in
      field conditions by combining free-air ozone exposure (1.2 * ambient) and
      infrared heaters (ambient +1.2&emsp14; degrees C). At leaf level measurements,
      elevated ozone decreased leaf net photosynthesis (P(n)), while the response to
      elevated temperature was dependent on leaf position within the foliage. This
      indicates that leaf position has to be taken into account when leaf level data
      are collected and applied. The ozone effect on P(n) was partly compensated for at
      elevated temperature, showing an interactive effect of the treatments. In
      addition, the ratio of photosynthesis to stomatal conductance (P(n)/g(s) ratio)
      was decreased by ozone, which suggests decreasing water use efficiency. At the
      plant level, the increasing leaf area at elevated temperature resulted in a
      considerable increase in photosynthesis and growth in both species.

PMID- 21856656
TI  - Seasonal changes of C and N non-structural compounds in the stem sapwood of adult
      sessile oak and beech trees.
AB  - We assessed the pools of non-structural nitrogen compounds (NSNC) through a year,
      thereby addressing the question of whether mature sessile oak [Quercus petraea
      (Matt.) Liebl.] and beech (Fagus sylvatica L.), which differ in wood anatomy and
      growth patterns, exhibit contrasting seasonal dynamics of NSNC pools as
      previously shown for non-structural carbohydrate (NSC) pools. Seasonal
      fluctuations of NSNC (amino acids and soluble proteins) and NSC (starch and
      soluble sugars) pools were analyzed in the inner and the outer stem sapwood. In
      oak, NSC showed marked seasonal variation within the stem sapwood (accumulation
      during winter and decrease during bud burst and early wood growth), whereas in
      beech seasonal fluctuations in NSC were of minor amplitude. Even if the
      distribution and intensity of the NSNC pools differed between the two species,
      NSNC of the stem sapwood did not show seasonal variation. The most significant
      change in NSNC pools was the seasonal fluctuation of protein composition. In both
      species, two polypeptides of 13 kDa (PP13) and 26 kDa (PP26) accumulated during
      the coldest period in parallel with starch to sugar conversion and disappeared
      with the onset of spring growth. The absence of seasonal changes in total soluble
      protein concentration suggests that the polypeptides are involved in the internal
      nitrogen (N) cycling of the stem rather than in N storage and remobilization to
      the other growing organs of the tree.

PMID- 21856657
TI  - Responses of stomatal conductance to simultaneous changes in two environmental
      factors.
AB  - To clarify interactions between stomatal responses to two simultaneous
      environmental changes, the rates of change in stomatal conductance were measured
      after simultaneously changing two environmental factors from the set of air
      humidity, leaf water potential (hydraulic environmental factors), air CO(2)
      concentration and light intensity (photosynthetic environmental factors). The
      stomatal responses to changes in leaf water potential were not significantly
      modified by any other simultaneous environmental change. A decrease in air
      humidity was followed by a decrease in stomatal conductance, and an increase in
      air humidity was followed by an increase in the conductance, irrespective of the
      character of the simultaneous change in the photosynthetic environmental factor.
      If the simultaneous change had an opposite effect on stomatal conductance, the
      rate of change in stomatal conductance was higher than the theoretical summed
      rate-the sum of the rate following one environmental change and the rate
      following another environmental change, measured separately. That is, the
      stomatal response to air humidity dominated over the responses to photosynthetic
      environmental factors. Yet, if the simultaneous change in photosynthetic factors
      had a codirectional effect on stomatal conductance, the rate of stomatal
      conductance change was lower than the theoretical summed rate. After a
      simultaneous change of two photosynthetic environmental factors, the rate of
      stomatal conductance change was very similar to the theoretical rate, if both the
      environmental changes had a codirectional effect on stomatal conductance. If the
      changes in the photosynthetic factors had opposite effects on stomatal
      conductance, the conductance increased, irrespective of the character of the
      increasing environmental factor. In drought-stressed trees, the rates of change
      in stomatal conductance tended to differ from the theoretical summed rates more
      than in well-watered trees. Stomatal closure following an increase in CO(2)
      concentration was the stomatal response that was most strongly suppressed by the
      response to another simultaneous environmental change. Six species of temperate
      deciduous trees were shown to be similar in their relations between the stomatal
      responses to two simultaneous environmental changes. The mechanism and ecological
      significance of the interactions between the two signal response pathways of
      stomata are discussed.

PMID- 21856659
TI  - Welsh government confirms commitment to dog welfare law.

PMID- 21856662
TI  - Tracking the spread of avian pox.

PMID- 21856667
TI  - Changing the SPCs of veterinary medicines.

PMID- 21856668
TI  - Continuous monitoring of glucose concentration in diabetic dogs.

PMID- 21856669
TI  - Detection of Chinese Q1 strain of infectious bronchitis virus in Europe.

PMID- 21856670
TI  - Providing fair access to veterinary postgraduate education.

PMID- 21856671
TI  - Have exotic grass species caused an increase in blades stuck in cats' throats?

PMID- 21856672
TI  - Bovine neonatal pancytopenia-like syndrome in dromedaries.

PMID- 21856673
TI  - Mycobacterium bovis mastitis in an alpaca and its implications.

PMID- 21856674
TI  - Incidence and predictors of anti-bradycardia pacing in patients with Anderson
      Fabry disease.
AB  - BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage
      disorder associated with bradyarrhythmias. We sought to examine the nature of
      conduction system abnormalities and the indications and determinants of anti
      bradycardia pacing in patients with AFD. METHODS AND RESULTS: We studied 204
      patients with AFD (49% male, mean age 42 years) in an observational,
      longitudinal, retrospective cohort study. At baseline, 5 (2.5%) patients had
      pacemakers for the treatment of bradycardias [4/5 (80%) for atrioventricular
      disease; 1/5 (20%) for sinus node disease]. PR interval <120 ms was observed in
      15 (7%); PR interval >200 ms in 6 (3%); QRS interval >120 ms 18 (9%); left QRS
      axis deviation in 16 (8%); and right-axis deviation in 2 (1%). Age was an
      independent determinant of prolonged PR interval, QRS duration and left QRS axis
      deviation. During follow-up (189 patients; 899 patient-years), 12 (6%) had a
      device implanted to treat spontaneously occurring bradyarrhythmias [5/12 (42%)
      for atrioventricular disease; 7/12 (58%) sinus node disease] with 8% 5-year
      cumulative incidence. Two independent predictors of future anti-bradycardia
      pacing were identified in a multivariable Cox model: QRS duration [hazard ratio
      (HR) 1.05, 95% confidence intervals (CI) 1.02-1.09, P= 0.001; receiver operating
      characteristic (ROC) curve c-statistic 0.726] and PR interval duration (HR 1.03,
      95% CI 1.004-1.060, P = 0.023; ROC curve c-statistic 0.548). QRS duration >=110
      ms at baseline had a sensitivity of 64%, specificity of 84%, 49% positive
      predictive value, and 91% negative predictive value for identifying patients
      likely to require anti-bradycardia pacing. CONCLUSION: In patients with AFD
      increasing age is associated with PR and QRS interval prolongation and left QRS
      axis deviation. Pacing for atrioventricular and sinus node disease is common and
      patients with QRS>=110 ms should be closely monitored for bradyarrhythmias.

PMID- 21856675
TI  - Electroanatomic remodelling of the pulmonary veins associated with age.
AB  - AIMS: Increasing age is a significant risk factor for developing atrial
      fibrillation (AF). Pulmonary vein (PV) triggers are critical in the mechanism of
      AF, but little is known of the substrate changes that occur within the PVs with
      ageing. Therefore, we sought to identify whether ageing is associated with
      electroanatomic changes within the pulmonary veins. METHODS AND RESULTS: Twenty
      five patients undergoing ablation for left-sided supraventricular tachycardia had
      high-density 3D electroanatomic maps of all four PVs created. Patients were
      divided into two groups: group 1 aged <50 years and group 2 aged >50 years. Mean
      voltage (MV), % low-voltage (LV < 0.5 mV), conduction, signal complexity, and PV
      muscle sleeve length and diameter were assessed. Age was 33 +/- 8 vs. 66 +/- 8
      years for groups 1 and 2, respectively (P < 0.001). Group 2 demonstrated: (i)
      lower MV within the PVs (1.66 +/- 1.1 vs. 1.88 +/- 1.1 mV, P < 0.001); (ii)
      increased % LV (5.0 vs. 1.1%, P < 0.001), and increased voltage heterogeneity
      within the PVs (65 +/- 14 vs. 55 +/- 8%, P < 0.05); (iii) regional and global
      conduction slowing in the PVs; and (iv) increased % complex signals within the
      PVs (1.4 vs. 0.4%, P = 0.009). There was no difference in PV sleeve length or
      diameter. CONCLUSION: Increasing age is associated with PV electroanatomic
      changes characterized by a significant reduction in PV voltage, conduction
      slowing, and increasing signal complexity. These observations provide new
      insights into the potential mechanisms behind the increased prevalence of AF with
      advancing age.

PMID- 21856676
TI  - Implantation of a biventricular implantable cardioverter-defibrillator guided by
      an electroanatomic mapping system.
AB  - AIMS: The aim of this study is to show the feasibility of a biventricular
      implantable cardioverter-defibrillator [cardiac resynchronization therapy (CRT)
      ICD] implantation using an electroanatomic navigation system and a low dose of
      fluoroscopy. Here four case reports of patients affected by dilated
      cardiomyopathy, who underwent cardiac resynchronization therapy, are described.
      METHODS AND RESULTS: During 2010, four patients were admitted to our Cardiology
      Department for implantation of an CRT-ICD device in primary prevention. All had
      an ejection fraction of <35% and were in New York Heart Association class III
      despite optimal medical therapy. The implantations were performed using the
      EnSite NavX system. All the leads were positioned in the cardiac chambers
      utilizing the three-dimensional navigation system and only using X-ray to check
      that the leads had been positioned correctly. To our knowledge, these cases are
      the first use of an electroanatomic system for implantation of an CRT-ICD device
      and in all four cases the cannulation of the coronary sinus (CS) was performed
      only using the mapping system. Electroanatomic navigation made it possible to
      minimize X-ray exposure during the implantation of the CRT-ICD device; in
      addition, the mapping system was used to choose the optimum position of the CS
      catheter using as reference the maximum activation delay between the two
      ventricles. CONCLUSIONS: The NavX system shows great potential during the
      implantation of an CRT-ICD device. It seems to be feasible, safe, and extremely
      beneficial in terms of a reduction in X-ray exposure. Furthermore, there is
      benefit of more detailed information and accuracy during the CS lead placement.

PMID- 21856677
TI  - Only as happy as the least happy child: multiple grown children's problems and
      successes and middle-aged parents' well-being.
AB  - OBJECTIVES: Middle-aged parents' well-being may be tied to successes and failures
      of grown children. Moreover, most parents have more than one child, but studies
      have not considered how different children's successes and failures may be
      associated with parental well-being. METHODS: Middle-aged adults (aged 40-60; N =
      633) reported on each of their grown children (n = 1,384) and rated their own
      well-being. Participants indicated problems each child had experienced in the
      past two years, rated their children's successes, as well as positive and
      negative relationship qualities. RESULTS: Analyses compared an exposure model
      (i.e., having one grown child with a problem or deemed successful) and a
      cumulative model (i.e., total problems or successes in the family). Consistent
      with the exposure and cumulative models, having one child with problems predicted
      poorer parental well-being and the more problems in the family, the worse
      parental well-being. Having one successful child did not predict well-being, but
      multiple grown children with higher total success in the family predicted
      enhanced parental well-being. Relationship qualities partially explained
      associations between children's successes and parental well-being. DISCUSSION:
      Discussion focuses on benefits and detriments parents derive from how grown
      progeny turn out and particularly the implications of grown children's problems.

PMID- 21856679
TI  - Plasma aldosterone levels in patients with coronary artery disease without heart
      failure or myocardial infarction: implications for pathophsiology, prognosis, and
      therapy.

PMID- 21856680
TI  - In search of vulnerable features of coronary plaques with optical coherence
      tomography: is it time to rethink the current methodological concepts?

PMID- 21856678
TI  - Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea
      in heart failure.
AB  - AIMS: Periodic breathing with central sleep apnoea (CSA) is common in heart
      failure patients and is associated with poor quality of life and increased risk
      of morbidity and mortality. We conducted a prospective, non-randomized, acute
      study to determine the feasibility of using unilateral transvenous phrenic nerve
      stimulation for the treatment of CSA in heart failure patients. METHODS AND
      RESULTS: Thirty-one patients from six centres underwent attempted transvenous
      lead placement. Of these, 16 qualified to undergo two successive nights of
      polysomnography-one night with and one night without phrenic nerve stimulation.
      Comparisons were made between the two nights using the following indices: apnoea
      hypopnoea index (AHI), central apnoea index (CAI), obstructive apnoea index
      (OAI), hypopnoea index, arousal index, and 4% oxygen desaturation index (ODI4%).
      Patients underwent phrenic nerve stimulation from either the right
      brachiocephalic vein (n = 8) or the left brachiocephalic or pericardiophrenic
      vein (n = 8). Therapy period was (mean +/- SD) 251 +/- 71 min. Stimulation
      resulted in significant improvement in the AHI [median (inter-quartile range); 45
      (39-59) vs. 23 (12-27) events/h, P = 0.002], CAI [27 (11-38) vs. 1 (0-5)
      events/h, P<= 0.001], arousal index [32 (20-42) vs. 12 (9-27) events/h, P =
      0.001], and ODI4% [31 (22-36) vs. 14 (7-20) events/h, P = 0.002]. No significant
      changes occurred in the OAI or hypopnoea index. Two adverse events occurred (lead
      thrombus and episode of ventricular tachycardia), though neither was directly
      related to phrenic nerve stimulation therapy. CONCLUSION: Unilateral transvenous
      phrenic nerve stimulation significantly reduces episodes of CSA and restores a
      more natural breathing pattern in patients with heart failure. This approach may
      represent a novel therapy for CSA and warrants further study.

PMID- 21856681
TI  - The prognostic meaning of the full spectrum of aVR ST-segment changes in acute
      myocardial infarction.
AB  - AIMS: ST-elevation in lead aVR is known to be associated with a worse prognosis
      in patients with acute ST elevation myocardial infarction (MI) but the
      significance of ST depression in lead aVR has been unclear. Infarction of the
      inferior apex of the left ventricle may not be appreciated on the standard 12
      lead electrocardiogram (ECG) except by observing ST depression in lead aVR which
      is reciprocal to lead V(7). We therefore determined the prognostic value of the
      full spectrum of aVR ST changes in patients presenting with acute ST elevation
      MI. METHODS AND RESULTS: Lead aVR ST level was measured on randomization and 60
      min ECGs in 15 315 patients with normal conduction from the HERO-2 trial. The
      outcome measure was 30-day mortality. aVR ST elevation >=1 mm was associated with
      higher 30-day mortality for both inferior (22.5% for >=1.5 mm and 13.2% for 1 mm)
      and anterior (23.5% for >=1.5 mm and 11.5% for 1 mm) infarction. In contrast,
      deeper aVR ST depression (0, 0.5, 1, and >=1.5 mm) was associated with higher
      mortality for anterior infarction (9.8, 13.2, 12.8, and 16.8%, respectively,
      trend P-value <0.0001) but not for inferior infarction. The resolution of aVR ST
      depression and ST elevation 60 min after fibrinolysis was associated with lower
      mortality. CONCLUSION: There is a U-shaped relationship between 30-day mortality
      and aVR ST level in patients presenting with anterior but not inferior ST
      elevation MI.

PMID- 21856682
TI  - Serum aldosterone and its relationship to left ventricular structure and geometry
      in patients with preserved left ventricular ejection fraction.
AB  - AIMS: Cardiac remodelling might be an important mechanism for aldosterone
      mediated cardiovascular (CV) morbidity and mortality. Previous studies relating
      aldosterone to left ventricular (LV) structure however revealed conflicting
      results. METHODS AND RESULTS: We aimed to evaluate the relationship of serum
      aldosterone concentration (SAC) and aldosterone-to-renin ratio (ARR) with
      echocardiographic parameters of LV remodelling in CV risk patients with preserved
      left ventricular ejection fraction (LVEF). We studied 1575 participants (54.1%
      female) with CV risk factors and LVEF >50% (61.7 +/- 6.1%). Of the total, 94.7%
      of patients had no overt heart failure. All patients underwent measurement of
      SAC, ARR, and comprehensive echocardiographic analysis. Overall, multivariate
      adjusted analysis of covariance (ANCOVA) showed a significant increase in LV mass
      (P= 0.001), LV mass index (P= 0.001), relative wall thickness (P= 0.011), and LV
      posterior wall thickness (P< 0.001) with increasing SAC. This overall association
      of SAC and LV remodelling was driven by a statistic significant effect
      exclusively in women. In multivariate logistic regression analysis higher SAC
      levels were independently related to concentric LV hypertrophy [odds ratio (OR;
      with 95% CI) by comparing SAC levels in the third gender-specific tertile with
      the first tertile: 1.87; 95% CI: 1.31-2.68; P= 0.001]. Higher SAC levels were
      positively related to concentric LVH in either sex. We observed no significant
      associations between the ARR and echocardiographic parameters of LV remodelling.
      CONCLUSION: Circulating aldosterone but not ARR levels are independently related
      to echocardiographic parameters of LV structure, particularly in women. Higher
      SAC however was related to concentric LVH in either sex. Our findings in a large
      CV risk cohort with preserved LVEF indicate aldosterone-mediated pro-hypertrophic
      effects as a potential pathway for structural alterations of the left ventricular
      myocardium.

PMID- 21856683
TI  - Prognostic variables in oligodendroglial tumors: a single-institution study of 95
      cases.
AB  - We analyzed the relationships among clinical variables, histology, 1p/19q status,
      and outcome in 95 patients with oligodendroglial tumors. The study enrolled adult
      patients who underwent first-time surgery for a supratentorial oligodendroglial
      tumor at Oslo University Hospital, Rikshospitalet. Tumors were: 27
      oligodendrogliomas, WHO grade II; 32 oligoastrocytomas, WHO grade II; 16
      anaplastic oligodendrogliomas, WHO grade III; 14 anaplastic oligoastrocytomas,
      WHO grade III; and 6 glioblastomas with a major oligodendroglial component, WHO
      grade IV. The clinical files were reviewed. Three neuropathologists evaluated the
      histological slides independently. Loss-of-heterozygosity analysis for 1p and 19q
      was performed by PCR. Favorable prognostic factors from univariate analyses
      included seizures as presenting symptom, female sex, location in the frontal
      lobe, low WHO grade, classic histology, absence of gemistocytic cells, and
      combined 1p/19q loss. Solitary 19q loss was a negative prognostic marker. 1p/19q
      status was of prognostic significance in both tumors with classic and nonclassic
      oligodendroglial histology. In the multivariate analysis, WHO grade II (P< .001),
      frontal tumor location (P= .002), and combined 1p/19q loss (P< .001) remained
      favorable prognostic variables. Our results suggest that tumor location, WHO
      grade, and 1p/19q status are important independent variables associated with
      survival in oligodendroglial tumors. The study suggests that solitary 19q loss is
      a negative prognostic variable and that 1p/19q loss is associated with prolonged
      survival also in oligodendroglial tumors without classic histology.

PMID- 21856684
TI  - Morbidity and mortality following acoustic neuroma excision in the United States:
      analysis of racial disparities during a decade in the radiosurgery era.
AB  - Acoustic neuromas present a challenging problem, with the major treatment
      modalities involving operative excision, stereotactic radiosurgery, observation,
      and fractionated stereotactic radiotherapy. The morbidity/mortality following
      excision may differ by patient race. To address this concern, the morbidity of
      acoustic neuroma excision was assessed on a nationwide level. The Nationwide
      Inpatient Sample from 1994-2003 was used for analysis. Only patients admitted for
      acoustic neuroma excision were included (International Classification of
      Diseases, 9th edition, Clinical Modification = 225.1; primary procedure code =
      04.01). Analysis was adjusted for several variables, including patient age, race,
      sex, primary payer for care, income in ZIP code of residence, surgeon caseload,
      and hospital caseload. Multivariate analyses revealed that postoperative
      mortality following acoustic neuroma excision was 0.5%, with adverse discharge
      disposition of 6.1%. The odds ratio for mortality in African Americans compared
      with Caucasians was 8.82 (95% confidence interval = 1.85-41.9, P = .006).
      Patients with high-caseload surgeons (more than 2 excisions/year), private
      insurance, and younger age had decreased mortality, better discharge disposition,
      and lower overall morbidity (P < .04). Neither hospital caseload nor median
      income were predictive factors. African Americans were 9 times more likely to die
      following surgery than Caucasians over a decade-long analysis. Given the
      relatively benign natural history of acoustic neuroma and the alarmingly
      increased mortality rate following surgical excision among older patients,
      African Americans, and patients receiving care from low-caseload surgeons,
      acoustic neuromas in these patient populations may be best managed by a more
      minimally invasive modality such as observation, fractionated stereotactic
      radiotherapy, or stereotactic radiosurgery.

PMID- 21856685
TI  - Graded functional diffusion map-defined characteristics of apparent diffusion
      coefficients predict overall survival in recurrent glioblastoma treated with
      bevacizumab.
AB  - Diffusion imaging has shown promise as a predictive and prognostic biomarker in
      glioma. We assessed the ability of graded functional diffusion maps (fDMs) and
      apparent diffusion coefficient (ADC) characteristics to predict overall survival
      (OS) in recurrent glioblastoma multiforme (GBM) patients treated with
      bevacizumab. Seventy-seven patients with recurrent GBMs were retrospectively
      examined. MRI scans were obtained before and approximately 6 weeks after
      treatment with bevacizumab. Graded fDMs were created by registering datasets to
      each patient's pretreatment scan and then performing voxel-wise subtraction
      between post- and pretreatment ADC maps. Voxels were categorized according to the
      degree of change in ADC within pretreatment fluid-attenuated inversion recovery
      (FLAIR) and contrast-enhancing regions of interest (ROIs). We found that the
      volume of tissue showing decreased ADC within both FLAIR and contrast-enhancing
      regions stratified OS (log-rank, P < .05). fDMs applied to contrast-enhancing
      ROIs more accurately predicted OS compared with fDMs applied to FLAIR ROIs.
      Graded fDMs (showing voxels with decreased ADC between 0.25 and 0.4 um(2)/ms)
      were more predictive of OS than traditional (single threshold) fDMs, and the
      predictive ability of graded fDMs could be enhanced even further by adding the
      ADC characteristics from the fDM-classified voxels to the analysis (log-rank, P <
      .001). These results demonstrate that spatially resolved diffusion-based tumor
      metrics are a powerful imaging biomarker of survival in patients with recurrent
      GBM treated with bevacizumab.

PMID- 21856687
TI  - A Dimensional Bus model for integrating clinical and research data.
AB  - OBJECTIVES: Many clinical research data integration platforms rely on the Entity
      Attribute-Value model because of its flexibility, even though it presents
      problems in query formulation and execution time. The authors sought more balance
      in these traits. MATERIALS AND METHODS: Borrowing concepts from Entity-Attribute
      Value and from enterprise data warehousing, the authors designed an alternative
      called the Dimensional Bus model and used it to integrate electronic medical
      record, sponsored study, and biorepository data. Each type of observational
      collection has its own table, and the structure of these tables varies to suit
      the source data. The observational tables are linked to the Bus, which holds
      provenance information and links to various classificatory dimensions that
      amplify the meaning of the data or facilitate its query and exposure management.
      RESULTS: The authors implemented a Bus-based clinical research data repository
      with a query system that flexibly manages data access and confidentiality,
      facilitates catalog search, and readily formulates and compiles complex queries.
      CONCLUSION: The design provides a workable way to manage and query mixed schemas
      in a data warehouse.

PMID- 21856686
TI  - Role of Eph/ephrin tyrosine kinase in malignant glioma.
AB  - Accumulating evidence has revealed that the tyrosine kinases play a major role in
      glioma proliferation and invasion. The largest family of tyrosine kinases, the
      Eph family, and its ligands, the ephrins, are frequently overexpressed in glioma,
      suggesting important roles for their bidirectional signals in glioma
      pathobiology. Ephs bind to cell surface-associated ephrin ligands on neighboring
      cells and have many biological functions during embryonic development of the
      central nervous system, including axon mapping, cell migration, and angiogenesis.
      Recent findings suggest that Eph/ephrin signaling affects glioma cell growth,
      migration, and invasion in vitro and in vivo. However, their roles in glioma seem
      complex, because both tumor growth promoter and suppressor potentials have been
      ascribed to Ephs and ephrins. Here, we review recent advances in research on the
      role of Eph/ephrin signaling in glioma and suggest that the Eph/ephrin system
      could be a potential target of glioma therapy.

PMID- 21856688
TI  - Tracking the delivery of prevention-oriented care among primary care providers
      who have adopted electronic health records.
AB  - The Primary Care Information Project is a New York City initiative aimed at
      improving population health through the improved delivery of preventive care. It
      has assisted with the adoption of a fully functional electronic health record
      (EHR) in over 300 primary care practices. Practices with EHRs automatically
      transmit summary data that can be used to track population health indicators for
      recommended preventive care. Early analysis, focusing on small practices with
      fewer than 10 providers serving Medicaid and uninsured populations, showed
      increases in the delivery of recommended services of 0.1-2.4% per month (p <=
      0.05). However, measurement of preventive care across this population is limited
      by some inconsistency of data transmission. This study shows that EHRs can be
      used to track the delivery of recommended preventive care across small primary
      care practices serving lower income communities in which few data are generally
      available for assessing population health.

PMID- 21856689
TI  - Retinal nerve fibre layer thickness, relative afferent pupillary defect and
      asymmetric glaucoma.

PMID- 21856690
TI  - Trans-corneal fine cannula aspiration: Rycroft cannula aspiration technique for
      sampling iris tumours.
AB  - AIM: To demonstrate a novel surgical technique for the accurate diagnosis of iris
      lesions using a minimally invasive aspiration cannula. METHOD: 12 consecutive
      patients underwent biopsy of iris lesions at the Ocular Oncology Service, Royal
      Hallamshire Hospital, Sheffield, UK. Samples were obtained using a novel
      technique called trans-corneal fine cannula aspiration. This comprised a 25
      gauge, Rycroft cannula aspiration technique performed by a single surgeon and
      samples transferred into alcohol-based tissue fixative. A specialist ophthalmic
      histopathologist performed a histological analysis of the samples. RESULTS: On
      average, the size of the specimens obtained in theatre ranged from 1 mm to 1.5 mm
      (maximum dimensions). This sample size allowed an unequivocal histological
      diagnosis in all 12 cases. In this study, 10 patients were diagnosed as having
      iris melanoma, one patient with metastatic adenocarcinoma and one patient with
      pigmented adenoma. CONCLUSIONS: This simple iris tumour biopsy technique provides
      sufficiently large sample sizes to obtain a firm histological diagnosis in 100%
      of cases performed so far. The sample sizes permitted not only morphological
      interpretation but also ancillary investigations such as immunohistochemistry.

PMID- 21856691
TI  - Population-based incidence of exudative age-related macular degeneration and
      ranibizumab treatment load.
AB  - BACKGROUND/AIMS: The use of intravitreal vascular endothelial growth factor
      antibodies for exudative age-related macular degeneration (AMD) has stressed
      ophthalmology services and drug budgets throughout the world. The authors study
      the population-based incidence of exudative AMD in Iceland and the use of
      intravitreal ranibizumab in a defined population. METHODS: This is a prospective
      study of 439 consecutive patients aged 60 years and older with exudative AMD
      starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to
      December 2009. All patients initially received three consecutive ranibizumab
      injections, with regular follow-up visits and re-treatment as needed. RESULTS: In
      total, 517 eyes from 439 patients received treatment for exudative AMD (mean age
      79 years). The annual incidence of exudative AMD in the population 60 years and
      older is 0.29%. The incidence increased with advancing age, double for patients
      85 years and older compared with those 75-79 years. Approximately 2400
      ranibizumab injections per 100,000 persons aged 60 years and older were given
      each year for exudative AMD. CONCLUSIONS: These data allow an estimation of the
      incidence of exudative AMD in a Caucasian population and the treatment load with
      ranibizumab, which may help plan anti-vascular endothelial growth factor
      treatment programmes and estimate costs.

PMID- 21856692
TI  - An exercise intervention to prevent falls in people with Parkinson's disease: a
      pragmatic randomised controlled trial.
AB  - OBJECTIVES: To compare the effectiveness of an exercise programme with usual care
      in people with Parkinson's disease (PD) who have a history of falls. DESIGN:
      Pragmatic randomised controlled trial. SETTING: Recruitment was from three
      primary and four secondary care organisations, and PD support groups in South
      West England. The intervention was delivered in community settings. PARTICIPANTS:
      People with PD, with a history of two or more falls in the previous year, who
      were able to mobilise independently. INTERVENTION: 10 week, physiotherapy led,
      group delivered strength and balance training programme with supplementary home
      exercises (intervention) or usual care (control). MAIN OUTCOME MEASURE: Number of
      falls during the (a) 10 week intervention period and (b) the 10 week follow-up
      period. RESULTS: 130 people were recruited and randomised (64 to the
      intervention; 66 to usual care). Seven participants (5.4%) did not complete the
      study. The incidence rate ratio for falls was 0.68 (95% CI 0.43 to 1.07, p=0.10)
      during the intervention period and 0.74 (95% CI 0.41 to 1.33, p=0.31) during the
      follow-up period. Statistically significant between group differences were
      observed in Berg balance, Falls Efficacy Scale-International scores and
      recreational physical activity levels. CONCLUSIONS: The study did not demonstrate
      a statistically significant between group difference in falls although the
      difference could be considered clinically significant. However, a type 2 error
      cannot be ruled out. The findings from this trial add to the evidence base for
      physiotherapy and exercise in the management of people with PD. Trial
      registration ISRCTN50793425.

PMID- 21856693
TI  - Langerhans cell histiocytosis with refractory central nervous system involvement
      responsive to infliximab.

PMID- 21856694
TI  - Assessment of medical occupational radiation doses in Costa Rica.
AB  - Participation of the University of Costa Rica (UCR) in activities in an IAEA
      Regional Project RLA/9/066 through training, equipment and expert missions, has
      enabled to setting up of a national personal monitoring laboratory. Since 2007,
      the UCR has been in charge of monitoring around 1800 medical radiation workers of
      the Social Security System. Individual external doses are measured with
      thermoluminescent dosemeter using a Harshaw 6600 Plus reader. The service has
      accreditation with ISO/IEC 17025:2005. Distribution of monitored medical
      personnel is as follows: 83 % in diagnostic radiology, 6 % in nuclear medicine
      and 6 % in radiotherapy. Preliminary values for the 75 percentile of annual
      H(p)(10) in mSv are: radiology 0.37; interventional radiology 0.41; radiotherapy
      0.53 and nuclear medicine 1.55. The service provided by the UCR in a steady and
      reliable way can help to implement actions to limit the doses received by the
      medical workers and optimise their radiation protection programs.

PMID- 21856696
TI  - Analyses of multiple-site and concurrent Chlamydia trachomatis serovar
      infections, and serovar tissue tropism for urogenital versus rectal specimens in
      male and female patients.
AB  - OBJECTIVES: The aims of this study were: to determine the incidence of concurrent
      infections on a serovar level; to determine the incidence of multiple anatomical
      infected sites on a detection and genotyping level and analyse site-specific
      serovar distribution; to identify tissue tropism in urogenital versus rectal
      specimens. METHODS: Chlamydia trachomatis-infected patients in two populations
      were analysed: 75 visiting the outpatient department of obstetrics and
      gynaecology of the MC Haaglanden, and 358 visiting the outpatient sexually
      transmitted disease clinic, The Hague, The Netherlands. The PACE 2 assay (Gen
      Probe) was used to detect C trachomatis from urethral, cervical, vaginal,
      oropharyngeal and anorectal swabs. C trachomatis genotyping was performed on all
      C trachomatis positive samples, using the CT-DT genotyping assay. RESULTS:
      Samples from 433 patients (256 female and 177 male) with confirmed C trachomatis
      infection were analysed. In 11 patients (2.6%), concurrent serovars in one
      anatomical sample site were present. In 62 (34.1%) female and four (9.3%) male
      patients, multiple sample site infections were found. A substantial percentage of
      women tested at the cervical/vaginal and rectal site were found to be positive at
      both sites (36.1%, 22/61). In men, D/Da and G/Ga serovars were more prevalent in
      rectal than urogenital specimens (p=0.0081 and p=0.0033, respectively), while
      serovar E was more prevalent in urogenital specimens (p=0.0012). CONCLUSIONS: The
      prevalence of multiple serovar infections is relatively low. Significant
      differences in serovar distribution are found in rectal specimens from men, with
      serovar G/Ga being the most prominent, suggesting tissue tropism.

PMID- 21856697
TI  - Occupational exposure to organic dust increases lung cancer risk in the general
      population.
AB  - BACKGROUND: Organic dust is a complex mixture of particulate matter from
      microbial, plant or animal origin. Occupations with exposure to animal products
      have been associated with an increased lung cancer risk, while exposure to
      microbial components (eg, endotoxin) has been associated with a decreased risk.
      To date there has not been a comprehensive evaluation of the possible association
      between occupational organic dust exposure (and its specific constituents) and
      lung cancer risk in the general population. METHODS: The SYNERGY project has
      pooled information on lifetime working and smoking from 13 300 lung cancer cases
      and 16 273 controls from 11 case-control studies conducted in Europe and Canada.
      A newly developed general population job-exposure matrix (assigning no, low or
      high exposure to organic dust, endotoxin, and contact with animals or fresh
      animal products) was applied to determine level of exposure. ORs for lung cancer
      were estimated by logistic regression, adjusted for age, sex, study, cigarette
      pack-years, time since quitting smoking, and ever employment in occupations with
      established lung cancer risk. RESULTS: Occupational organic dust exposure was
      associated with increased lung cancer risk. The second to the fourth quartile of
      cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24
      in a dose-dependent manner (p<0.001). This association remained in the highest
      quartile after restricting analyses to subjects without chronic obstructive
      pulmonary disease or asthma. No association was observed between lung cancer and
      exposure to endotoxin or contact with animals or animal products. CONCLUSION:
      Occupational exposure to organic dust was associated with increased lung cancer
      risk in this large pooled case-control study.

PMID- 21856698
TI  - The challenges of quality improvement reports and the urgent need for more of
      them.

PMID- 21856699
TI  - Genome-wide association studies in lung disease.
AB  - Genome-wide association studies (GWAS) have provided new insights into the
      molecular mechanisms of lung function and lung diseases. GWAS, and studies that
      build upon their findings, will continue to provide evidence aimed at advancing
      understanding of lung disease. This paper summarises the key features of a GWAS,
      references some recent findings and discusses how the chest physician can
      interpret the validity and utility of future GWAS and related studies.

PMID- 21856700
TI  - Will recording of lung function fluctuation open the door to internet-guided
      treatment of asthma?

PMID- 21856701
TI  - Increased mortality from infectious pneumonia after occupational exposure to
      inorganic dust, metal fumes and chemicals.
AB  - OBJECTIVES: There are epidemiological studies indicating that exposure to metal
      fumes is a risk factor for infectious pneumonia. Whether occupational exposure to
      other agents, such as inorganic dust or chemicals, also increases the risk for
      infectious pneumonia is not clear. The aim of the present study was to elucidate
      whether occupational exposure to respiratory pollutants and irritants increases
      the risk for infectious pneumonia. DESIGN: Prospective cohort study. Setting
      Swedish male construction workers. Participants 320,143 male construction workers
      exposed to inorganic dust (asbestos, man-made mineral fibres, dust from cement,
      concrete and quartz), wood dust, metal fumes and chemicals (organic solvents,
      diisocyanates and epoxi resins) or unexposed. Main outcome measures The cohort
      was followed from 1971 to 2003 and the main outcome measures were mortality to
      infectious pneumonia, lobar pneumonia or pneumococcal pneumonia. RRs were
      obtained by the person-years method and from Poisson regression models, adjusting
      for baseline values of age and smoking habits. RESULTS: Among men aged 20-64
      years there was increased mortality from infectious pneumonias among construction
      workers exposed to metal fumes (RR 2.31, 95% CI 1.35 to 3.95), inorganic dust (RR
      1.87, 95% CI 1.22 to 2.87) and chemicals (RR 1.91, 95% CI 1.37 to 3.22). The
      mortality was also increased from both lobar pneumonia and pneumococcal
      pneumonia. Among men aged 65-84 years the occupational exposure to inorganic dust
      and chemicals was associated with slightly increased mortality from infectious
      pneumonia. Among groups with mutually exclusive exposures there was increased
      mortality from infectious pneumonias among construction workers exposed to
      inorganic dust, but not among those exposed to wood dust or chemicals. There were
      no cases among workers exposed only to metal fumes. CONCLUSIONS: Our findings
      indicate that exposure to inorganic dust increases the mortality from infectious
      pneumonias, especially lobar pneumonia and pneumococcal pneumonia. The mechanism
      is unclear, but the effect may be mediated through induced airways inflammation.

PMID- 21856702
TI  - Managing passengers with stable respiratory disease planning air travel: British
      Thoracic Society recommendations.

PMID- 21856703
TI  - The Segond fracture: a clue to intra-articular knee pathology.
AB  - This short report presents the case of a 32-year-old man with a knee injury
      sustained while playing football. A plain radiograph revealed a Segond fracture
      and a subsequent MRI confirmed a complete anterior cruciate ligament rupture.
      While the Segond fracture, and its associated intra-articular pathology, is well
      recognised among orthopaedic surgeons, it is less well recognised among staff in
      the emergency department. The report aims to emphasise the importance of plain
      radiographs in patients with a history of knee injury and to highlight that this
      seemingly innocuous avulsion fracture may reveal more severe underlying
      pathology.

PMID- 21856704
TI  - Communication with survivors of motor vehicle crashes.
AB  - BACKGROUND: Communication with survivors of severe motor vehicle crashes is
      challenging for emergency physicians. The appropriate timing of death
      notification to survivors of severe motor vehicle crashes is unknown. OBJECTIVE:
      To determine communication preferences among survivors of motor vehicle crashes.
      METHODS: In this cross-sectional survey study, eligible participants included
      adult survivors of motor vehicle crashes in which there was a death, between 2005
      and 2009. Participants were interviewed and responses to 30 questions about
      communication were recorded verbatim. Responses were coded and grouped for
      statistical analysis. RESULTS: Among 26 eligible participants, 21 consented to
      participate (81% participation rate). Survivors' relationship to the deceased
      included spouse/significant other (33%), friend (24%), child (5%) and no
      relationship (38%). Survivors had been notified of the death in the prehospital
      setting (14%), in the emergency department (43%), or later in the inpatient
      setting (43%). Survivors were notified of the death by family members (43%),
      indirect communication (14%), police (10%), prehospital provider (10%), or friend
      (10%). Most participants (88%) had to ask directly to obtain information about
      the status of others in the crash. Participants demonstrated variable opinions
      about the ideal time of death notification: some recommended immediately (24%),
      in the emergency department (24%), in the inpatient setting (29%), or it depends
      on the circumstances (24%). CONCLUSIONS: Survivors of motor vehicles crashes are
      notified of fatalities most commonly by family members, most commonly in the
      hospital setting. Recommendations from survivors about the appropriate timing and
      setting for death notification varied significantly.

PMID- 21856705
TI  - Role of mean platelet volume in the diagnosis of acute coronary events.

PMID- 21856706
TI  - Distributing personal resuscitation manikins in an untrained population: how well
      are basic life support skills acquired?
AB  - BACKGROUND: Self-instruction with a DVD and a simple personal manikin is an
      effective alternative to traditional basic life support (BLS) courses. Objective
      To evaluate the effect of distributing DVD training kits to untrained laypersons.
      BLS skills were compared according to 2005 guidelines for resuscitation after 3.5
      months with those obtained in untrained laypersons who completed the same course
      with instructor facilitation. METHODS: BLS skills of 55 untrained laypersons were
      assessed using the Laerdal ResusciAnne and PC Skill Reporting System in a 3 min
      test and a total score (12-48 points) was calculated. The participants received a
      DVD training kit without instructions. The test was repeated after 3.5 months.
      Data were compared with data from a previous published study where participants
      completed the same course in groups with instructor facilitation. RESULTS: There
      was no statistically significant difference in the total score after 3.5 months.
      The 'DVD-self-instructor' group obtained 33 (29-37) points and the 'DVD-with
      instructor' group obtained 34 (32-37) points, p=0.16. The 'DVD-with instructor'
      group performed significantly better in checking responsiveness and had a
      significantly shorter 'total hands-off time' (s) (85 (76-94) vs 96 (82-120),
      p=0.002) and delay until first compression or ventilation group (29 s (17-40) vs
      33 s (22-48), p=0.04). CONCLUSIONS: Since no significant difference in total BLS
      score was found after 3.5 months between untrained laypersons who either
      completed a DVD-based BLS course in groups with instructor facilitation or
      received the same DVD training kit without instruction, the latter seems more
      efficient.

PMID- 21856707
TI  - A simple three-step dispatch rule may reduce lights and sirens responses to motor
      vehicle crashes.
AB  - INTRODUCTION: Most patients involved in motor vehicle crashes (MVCs) are not
      seriously injured. However, dispatch protocols require an ambulance be sent with
      lights and sirens (L&S) to the vast majority of MVCs. L&S have been shown to
      reduce response times minimally. The rate of injuries among prehospital workers
      is nearly 15 times higher among ambulances operating with L&S than those without.
      OBJECTIVE: To derive a dispatch rule to reduce the need for L&S response by using
      MVC characteristics that could easily be described by a 9-1-1 caller. The US
      Centers for Disease Control Field Triage Guidelines were used as the standard for
      requiring L&S response; it was assumed that if a patient did not require
      transport to a trauma centre, he/she did not need an L&S response. METHODS: Data
      were extracted from prehospital patient care reports (PCRs) of patients
      transported by ambulance to a level I trauma centre between July 2007 and June
      2008 with injuries sustained in MVCs. Patients with completed prehospital PCRs
      and hospital charts were included in the study. Five MVC characteristics were
      extracted that could easily be identified by a 9-1-1 caller. Using various
      permutations of these MVC characteristics, a dispatch rule was developed to
      determine when an ambulance should respond to an MVC without L&S. The sensitivity
      and specificity of this dispatch rule were calculated for both patients who met
      trauma centre triage criteria, and those who used trauma centre resources.
      RESULTS: 509 patients were included in the analysis. The following dispatch rule
      was developed for an ambulance response without L&S to a MVC: (1) the MVC does
      not occur on an interstate/highway, (2) and the MVC involves more than one car.
      AND (3) all patients are ambulatory. This dispatch rule was 95.9% sensitive and
      33.5% specific for patients who met trauma centre criteria, and 97.7% sensitive
      and 32.5% specific for patients who required trauma centre resources. The study
      was limited by the large number of patients for whom prehospital PCRs were not
      available. CONCLUSIONS: A simple three-step dispatch rule for MVCs can safely
      reduce L&S responses by one-third, as judged by need for transport to a trauma
      centre or use of trauma centre resources. Prospective validation is needed.

PMID- 21856708
TI  - Brodie's abscess.

PMID- 21856709
TI  - Atraumatic headache in US emergency departments: recent trends in CT/MRI
      utilisation and factors associated with severe intracranial pathology.
AB  - OBJECTIVES: To estimate recent trends in CT/MRI utilisation among patients
      seeking emergency care for atraumatic headache in the USA and to identify factors
      associated with a diagnosis of significant intracranial pathology (ICP) in these
      patients. DESIGN/SETTING/PARTICIPANTS: Data were obtained from the USA National
      Hospital Ambulatory Medical Care Survey of emergency department (ED) visits
      between 1998 and 2008. A cohort of atraumatic headache-related visits were
      identified using preassigned 'reason-for-visit' codes. Sample visits were
      weighted to provide national estimates. RESULTS: Between 1998 and 2008 the
      percentage of patients presenting to the ED with atraumatic headache who
      underwent imaging increased from 12.5% to 31.0% (p < 0.01) while the prevalence
      of ICP among those visits decreased from 10.1% to 3.5% (p < 0.05). The length of
      stay in the ED was 4.6 h (95% CI 4.4 to 4.8) for patients with headache who
      received imaging compared with 2.7 (95% CI 2.6 to 2.9) for those who did not. Of
      18 factors evaluated in patients with headache, 10 were associated with a
      significantly increased odds of an ICP diagnosis: age >= 50 years, arrival by
      ambulance, triage immediacy <15 min, systolic blood pressure >= 160 mm Hg or
      diastolic blood pressure >= 100 mm Hg and disturbance in sensation, vision,
      speech or motor function including neurological weakness. CONCLUSIONS: The use of
      CT/MRI for evaluation of atraumatic headache increased dramatically in EDs in the
      USA between 1998 and 2008. The prevalence of ICP among patients who received
      CT/MRI declined concurrently, suggesting a role for clinical decision support to
      guide more judicious use of imaging.

PMID- 21856710
TI  - Reducing violent injury.

PMID- 21856711
TI  - Adult difficult airway equipment in the emergency department.

PMID- 21856712
TI  - Surprising thoracic tumour mass.

PMID- 21856713
TI  - Diffuse intestinal pneumatosis and massive hepatic portal gas.

PMID- 21856714
TI  - Hyperconnectivity and slow synapses during early development of medial prefrontal
      cortex in a mouse model for mental retardation and autism.
AB  - Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental
      retardation propose that abnormal connectivity underlies deficits in attentional
      processing. We tested this theory by studying unitary synaptic connections
      between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks
      in the Fmr1-KO mouse model for mental retardation and autism. In line with
      predictions from neurocognitive theory, we found that neighboring pyramidal
      neurons were hyperconnected during a critical period in early mPFC development.
      Surprisingly, excitatory synaptic connections between Fmr1-KO pyramidal neurons
      were significantly slower and failed to recover from short-term depression as
      quickly as wild type (WT) synapses. By 4-5 weeks of mPFC development,
      connectivity rates were identical for both KO and WT pyramidal neurons and
      synapse dynamics changed from depressing to facilitating responses with similar
      properties in both groups. We propose that the early alteration in connectivity
      and synaptic recovery are tightly linked: using a network model, we show that
      slower synapses are essential to counterbalance hyperconnectivity in order to
      maintain a dynamic range of excitatory activity. However, the slow synaptic time
      constants induce decreased responsiveness to low-frequency stimulation, which may
      explain deficits in integration and early information processing in attentional
      neuronal networks in NDDs.

PMID- 21856716
TI  - Of time and troubles: patient involvement and the production of health care
      disparities.
AB  - Patient involvement in care practice has many and diverse proponents. It is
      endorsed by health care institutions and promoted by community agencies
      representing people with illness. A vast literature documents the benefits of
      patient involvement and describes ways to enable it. This article contributes to
      a critical literature on patient involvement by documenting the work done by
      women with cancer in relation to care timelines and in responding to troubles
      with care. We highlight continuities and disjunctures between this work, and
      discourses of patient involvement as they manifest in documents circulating at an
      Ontario cancer centre. In making visible the social and material resources that
      underpin successful involvement, the study shows how initiatives that endorse and
      promote 'the involved patient' can function to exacerbate health care and social
      disparities. As well, the study extends analysis of the individualization and
      privatization of health by showing how contemporary discourses of involvement
      enlist patients to monitor and sustain not only their own health, but also the
      health care they receive.

PMID- 21856715
TI  - A comparison of NT-proBNP and albuminuria for predicting cardiac events in
      patients with diabetes mellitus.
AB  - AIMS: Cardiovascular events are the most relevant events in patients with
      diabetes mellitus. We aimed to compare the predictive values of N-terminal pro
      brain natriuretic peptide (NT-proBNP) and the state-of-the-art marker,
      albuminuria, for cardiac events in diabetic patients. METHODS: In this
      prospective observational study we recruited 1071 patients with diabetes
      mellitus. NT-proBNP and albuminuria ? defined as a urinary albumin/creatinine
      ratio >30 mg/g were measured at baseline. Patients were followed during a mean
      observation period of 33.1 months. A total of 103 patients reached the defined
      endpoint (unplanned hospitalization due to a cardiac event or death). RESULTS:
      The mean duration of diabetes was 15 +/- 12 years and the mean HbA(1c) was 7.5 +/
      3.1%. At baseline, 23.7% of the patients presented with albuminuria and 36.6%
      had plasma NT-proBNP values >125 pg/ml. Multiple Cox regression analysis
      including age, gender, duration of diabetes HbA(1c), albuminuria, and lnNT-proBNP
      revealed that lnNT-proBNP (hazard ratio 2.314; 95% CI 1.914-2.798, p < 0.001) was
      a better predictor than albuminuria (HR 1.544; 95% CI 1.007-2.368, p = 0.047) or
      age (HR 1.030; 95% CI 1.008-1.053, p = 0.007). Calculating different Cox-models
      with (A) albuminuria, (B) NT-proBNP, or (C) both in the model revealed that the C
      index was best if NT-proBNP was entered in the model (C-index for A 0.735, for B
      0.809, and for C 0.786). Kaplan-Meier analysis demonstrated that albuminuria does
      not add substantial information if NT-proBNP is entered into the model.
      CONCLUSION: NT-proBNP was superior to albuminuria for predicting cardiac events.

PMID- 21856717
TI  - An item response theory analysis of the Problem Gambling Severity Index.
AB  - Increases in the availability of gambling heighten the need for a short screening
      measure of problem gambling. The Problem Gambling Severity Index (PGSI) is a
      brief measure that allows for the assessment of characteristics of gambling
      behavior and severity and its consequences. The authors evaluate the psychometric
      properties of the PGSI using item response theory methods in a representative
      sample of the urban adult population in South Africa (N = 3,000). The PGSI items
      were evaluated for differential item functioning (DIF) due to language
      translation. DIF was not detected. The PGSI was found to be unidimensional, and
      use of the nominal categories model provided additional information at higher
      values of the underlying construct relative to a simpler binary model. This study
      contributes to the growing literature supporting the PGSI as the screen of choice
      for assessing gambling problems in the general population.

PMID- 21856718
TI  - The short- to medium-term predictive accuracy of static and dynamic risk
      assessment measures in a secure forensic hospital.
AB  - Although violence risk assessment knowledge and practice has advanced over the
      past few decades, it remains practically difficult to decide which measures
      clinicians should use to assess and make decisions about the violence potential
      of individuals on an ongoing basis, particularly in the short to medium term.
      Within this context, this study sought to compare the predictive accuracy of
      dynamic risk assessment measures for violence with static risk assessment
      measures over the short term (up to 1 month) and medium term (up to 6 months) in
      a forensic psychiatric inpatient setting. Results showed that dynamic measures
      were generally more accurate than static measures for short- to medium-term
      predictions of inpatient aggression. These findings highlight the necessity of
      using risk assessment measures that are sensitive to important clinical risk
      state variables to improve the short- to medium-term prediction of aggression
      within the forensic inpatient setting. Such knowledge can assist with the
      development of more accurate and efficient risk assessment procedures, including
      the selection of appropriate risk assessment instruments to manage and prevent
      the violence of offenders with mental illnesses during inpatient treatment.

PMID- 21856719
TI  - Comparing the Pilates method with no exercise or lumbar stabilization for pain
      and functionality in patients with chronic low back pain: systematic review and
      meta-analysis.
AB  - OBJECTIVE: To perform a systematic review with meta-analyses that evaluates the
      effectiveness of the Pilates method on the pain and functionality outcome in
      adults with non-specific chronic low back pain. DATA SOURCES: The search was
      performed in the following databases: Medline, Embase, AMED, Cinahl, Lilacs,
      Scielo, SportDiscus, ProQuest, Web of Science, PEDro, Academic Search Premier and
      the Cochrane Central Register of Controlled Trials from 1950 to 2011; the
      following keywords were used: 'Pilates', 'Pilates-based', 'back exercises',
      'exercise therapy', 'low back pain', 'back pain' and 'backache'. REVIEW METHODS:
      The inclusion criteria were studies that assessed the effects of the Pilates
      method on patients with chronic low back pain. RESULTS: Five studies met the
      inclusion criteria. The total number of patients was 71 in the Pilates group and
      68 in the control group. Pilates exercise did not improve functionality
      (standardized mean difference (SMD = -1.34; 95% confidence interval (CI) -2.80,
      0.11; P = 0.07) or pain between Pilates and control groups (SMD = -1.99; 95% CI 
      4.35, 0.37; P = 0.10). Pilates and lumbar stabilization exercises presented no
      significant difference in functionality (mean difference (MD) = -0.31; 95% CI 
      1.02, 0.40; P = 0.39) or pain (MD = -0.31; 95% CI -1.02, 0.40; P = 0.39).
      CONCLUSION: The Pilates method did not improve functionality and pain in patients
      who have low back pain when compared with control and lumbar stabilization
      exercise groups.

PMID- 21856720
TI  - Health benefits of a view of nature through the window: a quasi-experimental
      study of patients in a residential rehabilitation center.
AB  - OBJECTIVE: To examine the health benefits of a bedroom window view to natural
      surroundings for patients undergoing a residential rehabilitation programme.
      DESIGN: Longitudinal quasi-experiment. SETTING: A residential rehabilitation
      centre. SUBJECTS: Two-hundred and seventy-eight coronary and pulmonary patients
      provided data at all measurement points during the programme. INTERVENTION:
      Blind, quasi-random allocation to a private bedroom with a panoramic view to
      natural surroundings or with a view either partially or entirely blocked by
      buildings. MAIN MEASURES: Self-reported physical and mental health (SF-12),
      subjective well-being, emotional states, use of the private bedroom and leisure
      activities. RESULTS: For women, a blocked view appeared to negatively influence
      change in physical health (time * view * gender interaction, F(4,504) = 2.51, P =
      0.04), whereas for men, a blocked view appeared to negatively influence change in
      mental health (time * view * gender interaction, F(4,504) = 5.67, P < 0.01).
      Pulmonary patients with a panoramic view showed greater improvement in mental
      health than coronary patients with such a view (time * view * diagnostic group
      interaction, F(4,504) = 2.76, P = 0.03). Those with a panoramic view to nature
      more often chose to stay in their bedroom when they wanted to be alone than those
      with a blocked view (odds ratio (OR) = 2.32, 95% confidence interval (CI) 1.08
      5.01). CONCLUSION: An unobstructed bedroom view to natural surroundings appears
      to have better supported improvement in self-reported physical and mental health
      during a residential rehabilitation programme, although the degree of change
      varied with gender and diagnostic group.

PMID- 21856721
TI  - Comparing the effects of eccentric training with eccentric training and static
      stretching exercises in the treatment of patellar tendinopathy. A controlled
      clinical trial.
AB  - OBJECTIVE: The aim of the present study was to investigate the effectiveness of
      eccentric training and eccentric training with static stretching exercises in the
      management of patellar tendinopathy. DESIGN: Controlled clinical trial. SETTING:
      Rheumatology and rehabilitation centre. SUBJECTS: Forty-three patients who had
      patellar tendinopathy for at least three months. They were allocated to two
      groups by alternative allocation. INTERVENTIONS: Group A (n = 22) was treated
      with eccentric training of patellar tendon and static stretching exercises of
      quadriceps and hamstrings and Group B (n = 21) received eccentric training of
      patellar tendon. All patients received five treatments per week for four weeks.
      OUTCOMES: Pain and function were evaluated using the VISA-P score at baseline, at
      the end of treatment (week 4), and six months (week 24) after the end of
      treatment. RESULTS: At the end of treatment, there was a rise in VISA-P score in
      both groups compared with baseline (P<0.0005, paired t test). There were
      significant differences in the VISA-P score between the groups at the end of
      treatment (+14; 10 to 18) and at the six-month follow-up (+19; 13 to 24);
      eccentric training and static stretching exercises produced the largest effect
      (P<0.0005, one-way ANOVA). CONCLUSIONS: Eccentric training and static stretching
      exercises is superior to eccentric training alone to reduce pain and improve
      function in patients with patellar tendinopathy at the end of the treatment and
      at follow-up.

PMID- 21856722
TI  - Responsiveness of the cervical Northern American Spine Society questionnaire
      (NASS) and the Short Form 36 (SF-36) in chronic whiplash.
AB  - OBJECTIVE: To determine and compare the sensitivity to change of the condition
      specific cervical Northern American Spine Society (NASS) and the generic Short
      Form 36 (SF-36). DESIGN: Prospective cohort study. SUBJECTS: One hundred and
      seventy five patients after whiplash injury. INTERVENTIONS: Four-week inpatient
      interdisciplinary pain management programme. MAIN MEASURES, ANALYSIS:
      Responsiveness of the NASS and the SF-36 was quantified by effect size and
      standardized response mean and compared within the same construct by the modified
      Jacknife test. Ability to detect improvement was compared using sensitivities
      determined from receiver operating characteristics curves. RESULTS: In pain, the
      NASS was comparable responsive to the SF-36 at the one-month follow-up (n = 175):
      effect sizes: 0.62 (NASS) versus 0.61 (SF-36), P = 0.914. The NASS was less
      responsive than the SF-36 in function: 0.23 versus 0.63, P < 0.001 and in
      pain+function: 0.35 versus 0.58 (P = 0.001). These relationships remained
      consistent using standardized response means, at the six-month follow-up (n =
      103), and in the comparison of the sensitivities. Sensitivities at one month,
      pain: 70% (NASS) versus 62% (SF-36), P = 0.234; function: 65% versus 80%, P =
      0.002; pain+function: 68% versus 78%, P = 0.035. The six-month data were similar.
      CONCLUSIONS: The generic SF-36 was more responsive in function and equally
      responsive in pain when compared to the condition-specific NASS. The SF-36 can be
      recommended as a responsive instrument for measurement of pain and function in
      chronic whiplash syndrome.

PMID- 21856723
TI  - FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS
      pathology from amyotrophic lateral sclerosis with FUS mutations.
AB  - Accumulation of the DNA/RNA binding protein fused in sarcoma as cytoplasmic
      inclusions in neurons and glial cells is the pathological hallmark of all
      patients with amyotrophic lateral sclerosis with mutations in FUS as well as in
      several subtypes of frontotemporal lobar degeneration, which are not associated
      with FUS mutations. The mechanisms leading to inclusion formation and fused in
      sarcoma-associated neurodegeneration are only poorly understood. Because fused in
      sarcoma belongs to a family of proteins known as FET, which also includes Ewing's
      sarcoma and TATA-binding protein-associated factor 15, we investigated the
      potential involvement of these other FET protein family members in the
      pathogenesis of fused in sarcoma proteinopathies. Immunohistochemical analysis of
      FET proteins revealed a striking difference among the various conditions, with
      pathology in amyotrophic lateral sclerosis with FUS mutations being labelled
      exclusively for fused in sarcoma, whereas fused in sarcoma-positive inclusions in
      subtypes of frontotemporal lobar degeneration also consistently immunostained for
      TATA-binding protein-associated factor 15 and variably for Ewing's sarcoma.
      Immunoblot analysis of proteins extracted from post-mortem tissue of
      frontotemporal lobar degeneration with fused in sarcoma pathology demonstrated a
      relative shift of all FET proteins towards insoluble protein fractions, while
      genetic analysis of the TATA-binding protein-associated factor 15 and Ewing's
      sarcoma gene did not identify any pathogenic variants. Cell culture experiments
      replicated the findings of amyotrophic lateral sclerosis with FUS mutations by
      confirming the absence of TATA-binding protein-associated factor 15 and Ewing's
      sarcoma alterations upon expression of mutant fused in sarcoma. In contrast, all
      endogenous FET proteins were recruited into cytoplasmic stress granules upon
      general inhibition of Transportin-mediated nuclear import, mimicking the findings
      in frontotemporal lobar degeneration with fused in sarcoma pathology. These
      results allow a separation of fused in sarcoma proteinopathies caused by FUS
      mutations from those without a known genetic cause based on neuropathological
      features. More importantly, our data imply different pathological processes
      underlying inclusion formation and cell death between both conditions; the
      pathogenesis in amyotrophic lateral sclerosis with FUS mutations appears to be
      more restricted to dysfunction of fused in sarcoma, while a more global and
      complex dysregulation of all FET proteins is involved in the subtypes of
      frontotemporal lobar degeneration with fused in sarcoma pathology.

PMID- 21856724
TI  - The C-terminal domain of the Salmonella enterica WbaP (UDP-galactose:Und-P
      galactose-1-phosphate transferase) is sufficient for catalytic activity and
      specificity for undecaprenyl monophosphate.
AB  - Two families of membrane enzymes catalyze the initiation of the synthesis of O
      antigen lipopolysaccharide. The Salmonella enterica Typhimurium WbaP is a
      prototypic member of one of these families. We report here the purification and
      biochemical characterization of the WbaP C-terminal (WbaP(CT)) domain harboring
      one putative transmembrane helix and a large cytoplasmic tail. An N-terminal
      thioredoxin fusion greatly improved solubility and stability of WbaP(CT) allowing
      us to obtain highly purified protein. We demonstrate that WbaP(CT) is sufficient
      to catalyze the in vitro transfer of galactose (Gal)-1-phosphate from uridine
      monophosphate (UDP)-Gal to the lipid carrier undecaprenyl monophosphate (Und-P).
      We optimized the in vitro assay to determine steady-state kinetic parameters with
      the substrates UDP-Gal and Und-P. Using various purified polyisoprenyl phosphates
      of increasing length and variable saturation of the isoprene units, we also
      demonstrate that the purified enzyme functions highly efficiently with Und-P,
      suggesting that the WbaP(CT) domain contains all the essential motifs to catalyze
      the synthesis of the Und-P-P-Gal molecule that primes the biosynthesis of
      bacterial surface glycans.

PMID- 21856725
TI  - Age at treatment predicts reason for discontinuation of TNF antagonists: data
      from the BIOBADASER 2.0 registry.
AB  - OBJECTIVES: To assess the retention rate of TNF antagonists in elderly patients
      suffering from chronic arthropathies and to identify predictive variables of
      discontinuation by inefficacy or by adverse events (AEs). METHODS: All patients
      treated with TNF antagonists in BIOBADASER 2.0, with a diagnosis of either RA or
      spondyloarthritis (SpA: AS and PsA) were included and classified as <65 (younger)
      or >=65 years of age (older) at start of the treatment. Cumulative incidence
      function for discontinuation (inefficacy or AE) was estimated as being the
      alternative reason for a competing risk. Competing-risks regression models were
      used to measure the association between study groups, covariates and reason for
      discontinuation. RESULTS: A total of 4851 patients were studied; 2957 RA (2291 in
      the younger group and 666 in the older group) and 1894 SpA (1795 in the younger
      group and 99 in the older group). Retention curves were statistically differently
      stratified by age groups, with the SpA younger group having the largest retention
      rate. Competing-risks regression models showed that in the older group, AEs were
      the most common reason for discontinuation regardless of the diagnosis of the
      patient and TNF antagonist molecule, whereas in the younger group, the most
      common cause of discontinuation was inefficacy. CONCLUSION: In conclusion,
      factors predicting discontinuation of TNF antagonists due to AEs are older age
      and diagnosis of RA. On the other hand, younger age predicts discontinuation due
      to lack of efficacy.

PMID- 21856726
TI  - UK guidelines for referral and assessment of adults for heart transplantation.
AB  - Patients with advanced heart failure have a dismal prognosis and poor quality of
      life. Heart transplantation provides an effective treatment for a subset of these
      patients. This article provides cardiologists with up-to-date information about
      referral for transplantation, the role of left ventricular assist devices prior
      to transplant, patient selection, waiting-list management and donor heart
      availability. Timing is of central importance; patients should be referred before
      complications (eg, cardiorenal syndrome or secondary pulmonary hypertension) have
      developed that will increase the risk of, or potentially contraindicate,
      transplantation. Issues related to heart failure aetiology, comorbidity and
      adherence to medical treatment are reviewed. Finally, the positive role that
      cardiologists can play in promoting and facilitating organ donation is discussed.

PMID- 21856727
TI  - Public access defibrillation: new developments for mass implementation.

PMID- 21856729
TI  - Why NT-proBNP should be less elevated in patients with short onset of atrial
      fibrillation and/or atrial thrombus.

PMID- 21856730
TI  - Percutaneous treatment of a chronic total occlusion for ST segment elevation
      myocardial infarction: an alternative in the case of early graft failure.

PMID- 21856731
TI  - Generation of a novel mouse model that recapitulates early and adult onset
      glycogenosis type IV.
AB  - Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder
      caused by deficiency of the glycogen branching enzyme (GBE). The diagnostic
      feature of the disease is the accumulation of a poorly branched form of glycogen
      known as polyglucosan (PG). The disease is clinically heterogeneous, with
      variable tissue involvement and age of disease onset. Absence of enzyme activity
      is lethal in utero or in infancy affecting primarily muscle and liver. However,
      residual enzyme activity (5-20%) leads to juvenile or adult onset of a disorder
      that primarily affects muscle as well as central and peripheral nervous system.
      Here, we describe two mouse models of GSD IV that reflect this spectrum of
      disease. Homologous recombination was used to insert flippase recognition target
      recombination sites around exon 7 of the Gbe1 gene and a phosphoglycerate kinase
      Neomycin cassette within intron 7, leading to a reduced synthesis of GBE. Mice
      bearing this mutation (Gbe1(neo/neo)) exhibit a phenotype similar to juvenile
      onset GSD IV, with wide spread accumulation of PG. Meanwhile, FLPe-mediated
      homozygous deletion of exon 7 completely eliminated GBE activity (Gbe1(-/-)),
      leading to a phenotype of lethal early onset GSD IV, with significant in utero
      accumulation of PG. Adult mice with residual GBE exhibit progressive
      neuromuscular dysfunction and die prematurely. Differently from muscle, PG in
      liver is a degradable source of glucose and readily depleted by fasting,
      emphasizing that there are structural and regulatory differences in glycogen
      metabolism among tissues. Both mouse models recapitulate typical histological and
      physiological features of two human variants of branching enzyme deficiency.

PMID- 21856732
TI  - Temporal and cell-specific deletion establishes that neuronal Npc1 deficiency is
      sufficient to mediate neurodegeneration.
AB  - Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage
      disorder caused by mutations in the NPC1 or NPC2 genes. Loss of function
      mutations in either gene disrupt intracellular lipid trafficking and lead to a
      clinically heterogeneous phenotype that invariably includes neurological
      dysfunction and early death. The mechanism by which impaired lipid transport
      leads to neurodegeneration is poorly understood. Here we used mice with a
      conditional null allele to establish the timing and cell type that underlie
      neurodegeneration due to Npc1 deficiency. We show that global deletion of Npc1 in
      adult mice leads to progressive weight loss, impaired motor function and early
      death in a time course similar to that resulting from germline deletion. These
      phenotypes are associated with the occurrence of characteristic neuropathology
      including patterned Purkinje cell loss, axonal spheroids and reactive gliosis,
      demonstrating that there is not a significant developmental component to NPC
      neurodegeneration. Furthermore, we show that these same changes occur when Npc1
      is specifically deleted only in neurons, establishing that neuronal deficiency is
      sufficient to mediate central nervous system (CNS) disease. In contrast,
      astrocyte-specific deletion does not impact behavioral phenotypes, CNS
      histopathology or synaptic function. We conclude that defects arising in neurons,
      but not in astrocytes, are the determining factor in the development of NPC
      neuropathology.

PMID- 21856734
TI  - "Population dynamics of crustaceans": introduction to the symposium.
AB  - Crustaceans are a globally-distributed faunal group, found across all habitats
      from the equator to the poles. They are an ideal focal assemblage for assessment
      of the impacts of climatic change and anthropogenic disturbance on nonmodel
      systems, such as how sea currents influence the movements of zooplankton
      communities in the open ocean, or how ecosystem processes affect phytoplanktonic
      species with restricted geographic distributions across a cluster of island lakes
      that could be a new model system for studies of speciation. This symposium
      introduced early-career researchers working in the fields of phylogeography,
      ecogenomics, fisheries management, and ecosystem processes with the aim of
      highlighting the different genetic and ecological approaches to the study of
      population dynamics of freshwater, estuarine, and marine crustacean species.

PMID- 21856735
TI  - The ancient lakes of Indonesia: towards integrated research on speciation.
AB  - Ancient lakes have provided considerable insights into the drivers of speciation
      and adaptive radiation in aquatic organisms. Most studies of species-flocks,
      however, focus only on a single group of organisms, and few have attempted to
      integrate geological, limnological, ecological, and genetic drivers of speciation
      on multiple species-flocks at various trophic levels. As such, there is a need
      for a comprehensive model system for research on speciation in aquatic
      environments where multiple radiations are investigated at various levels of
      biological organization (e.g., individual, population, and ecosystem) and placed
      in light of geographical and geological setting. The ancient Malili Lakes of
      Sulawesi, Indonesia, are ideal candidates for such a model, and represent the
      only hydrologically connected ancient lakes in the world. These lakes are
      characterized by ultra-oligotrophy and unique physicochemical conditions that
      govern the composition and production of planktonic communities. At higher
      trophic levels, there are three recurring trends: (1) low taxonomic richness and
      simple community structures, (2) adaptive radiations with trophic specialization,
      and (3) remarkably high endemism with evolutionary innovations throughout the
      lakes and species-flocks. Furthermore, the restricted geographic distributions of
      species-flocks within the Malili Lakes indicate that each lake constitutes a
      unique environment, and dispersal among lakes is limited, despite close
      contemporary connectivity. These observations suggest that ecological and
      evolutionary processes are regulated from the bottom up, and speciation is
      primarily facilitated by interspecific and intraspecific competition for limited
      resources. The Malili Lakes represent an outstanding natural model for
      integrative research into speciation as they offer the opportunity to explore the
      roles of geography, dispersal, and selection in the radiation of aquatic
      organisms.

PMID- 21856733
TI  - Network reconfiguration and neuronal plasticity in rhythm-generating networks.
AB  - Neuronal networks are highly plastic and reconfigure in a state-dependent manner.
      The plasticity at the network level emerges through multiple intrinsic and
      synaptic membrane properties that imbue neurons and their interactions with
      numerous nonlinear properties. These properties are continuously regulated by
      neuromodulators and homeostatic mechanisms that are critical to maintain not only
      network stability and also adapt networks in a short- and long-term manner to
      changes in behavioral, developmental, metabolic, and environmental conditions.
      This review provides concrete examples from neuronal networks in invertebrates
      and vertebrates, and illustrates that the concepts and rules that govern neuronal
      networks and behaviors are universal.

PMID- 21856736
TI  - PTPan--overcoming memory limitations in oligonucleotide string matching for
      primer/probe design.
AB  - MOTIVATION: Nucleic acid diagnostics has high demands for non-heuristic exact and
      approximate oligonucleotide string matching concerning in silico primer/probe
      design in huge nucleic acid sequence collections. Unfortunately, public sequence
      repositories grow much faster than computer hardware performance and main memory
      capacity do. This growth imposes severe problems on existing oligonucleotide
      primer/probe design applications necessitating new approaches based on space
      efficient indexing structures. RESULTS: We developed PTPan (spoken Peter Pan,
      'PT' is for Position Tree, the earlier name of suffix trees), a space-efficient
      indexing structure for approximate oligonucleotide string matching in nucleic
      acid sequence data. Based on suffix trees, it combines partitioning, truncation
      and a new suffix tree stream compression to deal with large amounts of aligned
      and unaligned data. PTPan operates efficiently in main memory and on secondary
      storage, balancing between memory consumption and runtime during construction and
      application. Based on PTPan, applications supporting similarity search and
      primer/probe design have been implemented, namely FindFamily, ProbeMatch and
      ProbeDesign. All three use a weighted Levenshtein distance metric for
      approximative queries to find and rate matches with indels as well as
      substitutions. We integrated PTPan in the worldwide used software package ARB to
      demonstrate usability and performance. Comparing PTPan and the original ARB index
      for the very large ssu-rRNA database SILVA, we recognized a shorter construction
      time, extended functionality and dramatically reduced memory requirements at the
      price of expanded, but very reasonable query times. PTPan enables indexing of
      huge nucleic acid sequence collections at reasonable application response times.
      Not being limited by main memory, PTPan constitutes a major advancement regarding
      rapid oligonucleotide string matching in primer/probe design now and in the
      future facing the enormous growth of molecular sequence data. AVAILABILITY:
      Supplementary Material, PTPan stand-alone library and ARB-PTPan binary on
      http://ptpan.lrr.in.tum.de/. CONTACT: meierh@in.tum.de SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 21856737
TI  - Comparative analysis of algorithms for next-generation sequencing read alignment.
AB  - MOTIVATION: The advent of next-generation sequencing (NGS) techniques presents
      many novel opportunities for many applications in life sciences. The vast number
      of short reads produced by these techniques, however, pose significant
      computational challenges. The first step in many types of genomic analysis is the
      mapping of short reads to a reference genome, and several groups have developed
      dedicated algorithms and software packages to perform this function. As the
      developers of these packages optimize their algorithms with respect to various
      considerations, the relative merits of different software packages remain
      unclear. However, for scientists who generate and use NGS data for their specific
      research projects, an important consideration is choosing the software that is
      most suitable for their application. RESULTS: With a view to comparing existing
      short read alignment software, we develop a simulation and evaluation suite,
      Seal, which simulates NGS runs for different configurations of various factors,
      including sequencing error, indels and coverage. We also develop criteria to
      compare the performances of software with disparate output structure (e.g. some
      packages return a single alignment while some return multiple possible
      alignments). Using these criteria, we comprehensively evaluate the performances
      of Bowtie, BWA, mr- and mrsFAST, Novoalign, SHRiMP and SOAPv2, with regard to
      accuracy and runtime. CONCLUSION: We expect that the results presented here will
      be useful to investigators in choosing the alignment software that is most
      suitable for their specific research aims. Our results also provide insights into
      the factors that should be considered to use alignment results effectively. Seal
      can also be used to evaluate the performance of algorithms that use deep
      sequencing data for various purposes (e.g. identification of genomic variants).
      AVAILABILITY: Seal is available as open source at http://compbio.case.edu/seal/.
      CONTACT: matthew.ruffalo@case.edu SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 21856738
TI  - Detecting biological network organization and functional gene orthologs.
AB  - SUMMARY: We developed a package TripletSearch to compute relationships within
      triplets of genes based on Roundup, an orthologous gene database containing >1500
      genomes. These relationships, derived from the coevolution of genes, provide
      valuable information in the detection of biological network organization from the
      local to the system level, in the inference of protein functions and in the
      identification of functional orthologs. To run the computation, users need to
      provide the GI IDs of the genes of interest. AVAILABILITY:
      http://wall.hms.harvard.edu/sites/default/files/tripletSearch.tar.gz CONTACT:
      dpwall@hms.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21856739
TI  - Regulation of protein tyrosine phosphatases by reversible oxidation.
AB  - Oxidation of the catalytic cysteine of protein-tyrosine phosphatases (PTP), which
      leads to their reversible inactivation, has emerged as an important regulatory
      mechanism linking cellular tyrosine phosphorylation and signalling by reactive
      oxygen or -nitrogen species (ROS, RNS). This review focuses on recent findings
      about the involved pathways, enzymes and biochemical mechanisms. Both the general
      cellular redox state and extracellular ligand-stimulated ROS production can cause
      PTP oxidation. Members of the PTP family differ in their intrinsic susceptibility
      to oxidation, and different types of oxidative modification of the PTP catalytic
      cysteine can occur. The role of PTP oxidation for physiological signalling
      processes as well as in different pathologies is described on the basis of well
      investigated examples. Criteria to establish the causal involvement of PTP
      oxidation in a given process are proposed. A better understanding of mechanisms
      leading to selective PTP oxidation in a cellular context, and finding ways to
      pharmacologically modulate these pathways are important topics for future
      research.

PMID- 21856740
TI  - Strong activation of ether-a-go-go-related gene 1 K+ channel isoforms by NS1643
      in human embryonic kidney 293 and Chinese hamster ovary cells.
AB  - Two different mechanisms leading to increased current have been described for the
      small-molecule human ether-a-go-go-related gene (herg) activator NS1643 [1,3-bis
      (2-hydroxy-5-trifluoromethylphenyl)-urea]. On herg1a channels expressed in
      Xenopus laevis oocytes, it mainly acts via attenuation of inactivation and for
      rat (r) erg1b channels expressed in human embryonic kidney (HEK)-293 cells, it
      strongly shifts the activation curve to the left. We now investigated the NS1643
      effects on erg1b channels in more detail and performed comparative experiments
      with rat and human erg1a in different expression systems. Significant differences
      were observed between expression systems, but not between the rat and human
      isoform. In HEK-293 or Chinese hamster ovary (CHO) cells, activation of rat erg1b
      channels occurred in a dose-dependent manner with a maximum current increase of
      300% obtained with 10 MUM NS1643. In contrast, the NS1643-induced strong leftward
      shift in the voltage dependence of activation further increased with higher drug
      concentration, needed more time to develop, and exhibited use dependence.
      Coexpression of KCNE1 or KCNE2 did not attenuate this NS1643 effect on erg1
      channel activation and did thus not mimic the lower drug potency on this
      parameter observed in oocytes. NS1643 (10 MUM) slowed erg1b channel deactivation
      and recovery from inactivation without significant changes in activation and
      inactivation kinetics. With the exception of accelerated activation, NS1643
      affected erg1a channels similarly, but the effect was less pronounced than in
      erg1b or erg1a/1b channels. It is noteworthy that rerg1b and herg1a inactivation
      estimated from fully activated current voltage relationships were unaltered in
      the continued presence of 10 MUM NS1643 in the mammalian expression systems,
      indicating qualitative differences from NS1643 effects in X. laevis oocytes.

PMID- 21856741
TI  - Functional characterization of the alpha5(Asn398) variant associated with risk
      for nicotine dependence in the alpha3beta4alpha5 nicotinic receptor.
AB  - Smoking is a major cause for premature death. Work aimed at identifying genetic
      factors that contribute to nicotine addiction has revealed several single
      nucleotide polymorphisms (SNPs) that are linked to smoking-related behaviors such
      as nicotine dependence and level of smoking. One of these SNPs leads to an
      aspartic acid-to-asparagine substitution in the nicotinic receptor alpha5 subunit
      at amino acid position 398 [rs16969968; alpha5(Asn398)]. The alpha5 subunit is
      expressed both in the brain and in the periphery. In the brain, it associates
      with the alpha4 and beta2 subunits to form alpha4beta2alpha5 receptors. In the
      periphery, the alpha5 subunit combines with the alpha3 and beta4 subunits to form
      the major ganglionic postsynaptic nicotinic receptor subtype. The
      alpha3beta4alpha5 receptor regulates a variety of autonomic responses such as
      control of cardiac rate, blood pressure, and perfusion. In this paradigm, the
      alpha5(Asn398) variant may act by regulating autonomic responses that may affect
      nicotine intake by humans. Here, we have investigated the effect of the
      alpha5(Asn398) variant on the function of the alpha3beta4alpha5 receptor. The
      wild-type or variant alpha5 subunits were coexpressed with the alpha3 and beta4
      subunits in human embryonic kidney 293 cells. The properties of the receptors
      were studied using whole-cell and single-channel electrophysiology. The data
      indicate that the introduction of the alpha5(Asn398) mutation has little effect
      on the pharmacology of receptor activation, receptor desensitization, or single
      channel properties. We propose that the effect of the alpha5(Asn398) variant on
      nicotine use is not mediated by an action on the physiological or pharmacological
      properties of the alpha3beta4alpha5 subtype.

PMID- 21856742
TI  - Bovine serum albumin decreases Km values of human UDP-glucuronosyltransferases
      1A9 and 2B7 and increases Vmax values of UGT1A9.
AB  - The human UDP-glucuronosyltransferase (UGT) enzymes UGT1A9 and UGT2B7 play
      important roles in the hepatic glucuronidation of many drugs. The presence of
      bovine serum albumin (BSA) during in vitro assays was recently reported to lower
      the K(m) values of both these UGTs for their aglycone substrates without
      affecting the corresponding V(max) values. Nonetheless, using the specific
      substrates entacapone and zidovudine (AZT) for UGT1A9 and UGT2B7, respectively,
      and using an improved ultrafiltration method for measuring drug binding to BSA
      and to biological membranes, we found that the presence of BSA during the
      glucuronidation reaction leads to a large increase in the V(max) value of UGT1A9,
      in addition to lowering its K(m) value. On the other hand, in the case of UGT2B7,
      our results agree with the previously described effect of BSA, namely lowering
      the K(m) value without a large effect on the enzyme's V(max) value. The
      unexpected BSA effect on UGT1A9 was independent of the expression system because
      it was found in a recombinant enzyme that was expressed in baculovirus-infected
      insect cells as well as in the native enzyme in human liver microsomes. Moreover,
      the effect of BSA on the kinetics of 4-methylumbelliferone glucuronidation by
      recombinant UGT1A9 was similar to its effect on entacapone glucuronidation.
      Contrary to the aglycone substrates, the effect of BSA on the apparent K(m) of
      UGT1A9 for the cosubstrate UDP-alpha-D-glucuronic acid was nonsignificant. Our
      findings call for further investigations of the BSA effects on different UGTs and
      the inhibitors that it may remove.

PMID- 21856743
TI  - What can be done to reduce mortality from paracetamol overdoses? A patient
      interview study.
AB  - BACKGROUND: Paracetamol (acetaminophen) is the most common self-poisoning agent
      in the UK and a leading cause of fatal hepatotoxicity. Following legislation in
      1998 to limit pack sizes, beneficial effects on paracetamol-related mortality and
      morbidity were reported in England. However, there are still over 100 deaths a
      year and evidence of breaches of sales guidelines. AIM: To investigate
      characteristics of people taking larger paracetamol overdoses and compliance with
      sales guidelines, to inform possible further initiatives to reduce paracetamol
      fatalities. DESIGN AND METHODS: Interview study of 60 general hospital patients
      who took overdoses of over 16 paracetamol tablets (8 g). RESULTS: Half of all
      paracetamol overdoses involved over 16 tablets. Patients were predominantly young
      (three-quarters aged 16-40 years) and female (58.3%); over half (53.3%) had taken
      a previous paracetamol overdose. Three-quarters said they wanted to die. Half
      took the overdose within an hour of first thinking of it, half (53.3%) took
      tablets already in the home and 58.3% bought tablets specifically for the
      overdose. Ten people tried to buy more than 32 tablets in one transaction; four
      succeeded. Most knew that a paracetamol overdose could cause death or permanent
      damage (88.3%) and harm the liver (80.0%) but 70.0% thought they would lose
      consciousness. Warnings on packs had little deterrent effect. Media and internet
      influences were identified. Patients chose paracetamol because it was cheap and
      easily available. CONCLUSIONS: Further measures to reduce breaches of sales
      guidelines and the dangers of paracetamol overdose are required. Media and
      internet site producers should follow guidelines on reporting suicide.

PMID- 21856744
TI  - Effects of photoacoustic imaging and photothermal ablation therapy mediated by
      targeted hollow gold nanospheres in an orthotopic mouse xenograft model of
      glioma.
AB  - Advancements in nanotechnology have made it possible to create multifunctional
      nanostructures that can be used simultaneously to image and treat cancers. For
      example, hollow gold nanospheres (HAuNS) have been shown to generate intense
      photoacoustic signals and induce efficient photothermal ablation (PTA) therapy.
      In this study, we used photoacoustic tomography, a hybrid imaging modality, to
      assess the intravenous delivery of HAuNS targeted to integrins that are
      overexpressed in both glioma and angiogenic blood vessels in a mouse model of
      glioma. Mice were then treated with near-infrared laser, which elevated tumor
      temperature by 20.7 degrees C. We found that PTA treatment significantly
      prolonged the survival of tumor-bearing mice. Taken together, these results show
      the feasibility of using a single nanostructure for image-guided local tumor PTA
      therapy with photoacoustic molecular imaging.

PMID- 21856745
TI  - miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in
      lung cancer.
AB  - Lung cancers with neuroendocrine (NE) features are often very aggressive but the
      underlying molecular mechanisms remain elusive. The transcription factor
      ASH1/ASCL1 is a master regulator of pulmonary NE cell development that is
      involved in the pathogenesis of lung cancers with NE features (NE-lung cancers).
      Here we report the definition of the microRNA miR-375 as a key downstream
      effector of ASH1 function in NE-lung cancer cells. miR-375 was markedly induced
      by ASH1 in lung cancer cells where it was sufficient to induce NE
      differentiation. miR-375 upregulation was a prerequisite for ASH1-mediated
      induction of NE features. The transcriptional coactivator YAP1 was determined to
      be a direct target of miR-375. YAP1 showed a negative correlation with miR-375 in
      a panel of lung cancer cell lines and growth inhibitory activities in NE-lung
      cancer cells. Our results elucidate an ASH1 effector axis in NE-lung cancers that
      is functionally pivotal in controlling NE features and the alleviation from YAP1
      mediated growth inhibition.

PMID- 21856746
TI  - Caregiver confidence: does it predict changes in disability among elderly home
      care recipients?
AB  - PURPOSE OF THE STUDY: The primary aim of this investigation was to determine
      whether caregiver confidence in their care recipients' functional capabilities
      predicts changes in the performance of activities of daily living (ADL) among
      elderly home care recipients. A secondary aim was to explore how caregiver
      confidence and care recipient functional self-efficacy jointly influence changes
      in ADL performance over time. DESIGN AND METHODS: The sample included 5,138
      elderly recipients of home and community-based long-term care in Michigan. ADL
      performance was assessed multiple times over a 2-year period. Caregiver
      confidence was measured at baseline with a single item. Multilevel modeling was
      used to estimate the effect of caregiver confidence on changes in ADL performance
      over time, controlling for baseline self-efficacy, ADL performance, and other
      factors that might confound the relationship. Based on caregiver confidence and
      elder self-efficacy, we created 4 groups of elder caregiver dyads to explore the
      combined effect of caregiver and elder confidence on change in ADL performance.
      RESULTS: Elders whose caregivers were confident in their capacity for greater
      functional independence experienced greater improvement in ADL performance than
      those whose caregivers were not confident. Elders in dyads in which both members
      expressed confidence experienced more improvement in ADL performance than those
      in dyads in which either one or both members lacked confidence. IMPLICATIONS:
      Interventions to strengthen caregivers' confidence in their care recipients'
      functional capabilities may slow functional losses among home care elders.
      Additional research is needed to confirm these findings and identify the factors
      that influence caregiver confidence.

PMID- 21856747
TI  - Ligand-dependent corepressor acts as a novel androgen receptor corepressor,
      inhibits prostate cancer growth, and is functionally inactivated by the Src
      protein kinase.
AB  - The activated androgen receptor (AR) promotes prostate cancer (PCa) growth. AR
      antagonists repress the AR by recruitment of corepressors. Not much is known
      about the inactivation of AR by corepressors in the presence of agonists
      (androgens). Here we show that the corepressor LCoR acts as an androgen-dependent
      corepressor that represses human PCa growth in vivo. In line with this,
      progressive decrease of ligand-dependent corepressor expression was observed in
      the PCa TRAMP mouse model with increasing age. LCoR interacts with AR and is
      recruited to chromatin in an androgen-induced manner. Unexpectedly, the LXXLL
      motif of LCoR is dispensable for interaction with the AR. Rather, the data
      indicate that LCoR interacts with the AR DNA binding domain on DNA.
      Interestingly, the interaction of LCoR with AR is inhibited by signaling pathways
      that are associated with androgen-independent PCa. Here we also show that the Src
      kinase inactivates the corepressive function of LCoR. Interfering with endogenous
      Src function by a dominant negative Src mutant, the growth inhibitory activity of
      LCoR is enhanced in vivo in a xenograft mouse model system. Thus, our studies
      indicate a role of LCoR as an AR corepressor and a tumor suppressor. Further, the
      decreased expression or inactivation of LCoR is as an important step toward PCa
      carcinogenesis in vivo.

PMID- 21856748
TI  - The identification of a novel protein involved in molybdenum cofactor
      biosynthesis in Escherichia coli.
AB  - In the second step of the molybdenum cofactor (Moco) biosynthesis in Escherichia
      coli, the l-cysteine desulfurase IscS was identified as the primary sulfur donor
      for the formation of the thiocarboxylate on the small subunit (MoaD) of MPT
      synthase, which catalyzes the conversion of cyclic pyranopterin monophosphate to
      molybdopterin (MPT). Although in Moco biosynthesis in humans, the
      thiocarboxylation of the corresponding MoaD homolog involves two
      sulfurtransferases, an l-cysteine desulfurase, and a rhodanese-like protein, the
      rhodanese-like protein in E. coli remained enigmatic so far. Using a reverse
      approach, we identified a so far unknown sulfurtransferase for the MoeB-MoaD
      complex by protein-protein interactions. We show that YnjE, a three-domain
      rhodanese-like protein from E. coli, interacts with MoeB possibly for sulfur
      transfer to MoaD. The E. coli IscS protein was shown to specifically interact
      with YnjE for the formation of the persulfide group on YnjE. In a defined in
      vitro system consisting of MPT synthase, MoeB, Mg-ATP, IscS, and l-cysteine, YnjE
      was shown to enhance the rate of the conversion of added cyclic pyranopterin
      monophosphate to MPT. However, YnjE was not an enhancer of the cysteine
      desulfurase activity of IscS. This is the first report identifying the rhodanese
      like protein YnjE as being involved in Moco biosynthesis in E. coli. We believe
      that the role of YnjE is to make the sulfur transfer from IscS for Moco
      biosynthesis more specific because IscS is involved in a variety of different
      sulfur transfer reactions in the cell.

PMID- 21856749
TI  - Sphingomyelin synthase 1-generated sphingomyelin plays an important role in
      transferrin trafficking and cell proliferation.
AB  - Transferrin (Tf) endocytosis and recycling are essential for iron uptake and the
      regulation of cell proliferation. Tf and Tf receptor (TfR) complexes are
      internalized via clathrin-coated pits composed of a variety of proteins and
      lipids and pass through early endosomes to recycling endosomes. We investigated
      the role of sphingomyelin (SM) synthases (SMS1 and SMS2) in clathrin-dependent
      trafficking of Tf and cell proliferation. We employed SM-deficient lymphoma cells
      that lacked SMSs and that failed to proliferate in response to Tf. Transfection
      of SMS1, but not SMS2, enabled these cells to incorporate SM into the plasma
      membrane, restoring Tf-mediated proliferation. SM-deficient cells showed a
      significant reduction in clathrin-dependent Tf uptake compared with the parental
      SM-producing cells. Both SMS1 gene transfection and exogenous short-chain SM
      treatment increased clathrin-dependent Tf uptake in SM-deficient cells, with the
      Tf being subsequently sorted to Rab11-positive recycling endosomes. We observed
      trafficking of the internalized Tf to late/endolysosomal compartments, and this
      was not dependent on the clathrin pathway in SM-deficient cells. Thus, SMS1
      mediated SM synthesis directs Tf-TfR to undergo clathrin-dependent endocytosis
      and recycling, promoting the proliferation of lymphoma cells.

PMID- 21856750
TI  - Senescence-associated barley NAC (NAM, ATAF1,2, CUC) transcription factor
      interacts with radical-induced cell death 1 through a disordered regulatory
      domain.
AB  - Senescence in plants involves massive nutrient relocation and age-related cell
      death. Characterization of the molecular components, such as transcription
      factors (TFs), involved in these processes is required to understand senescence.
      We found that HvNAC005 and HvNAC013 of the plant-specific NAC (NAM, ATAF1,2, CUC)
      TF family are up-regulated during senescence in barley (Hordeum vulgare). Both
      HvNAC005 and HvNAC013 bound the conserved NAC DNA target sequence. Computational
      and biophysical analyses showed that both proteins are intrinsically disordered
      in their large C-terminal domains, which are transcription regulatory domains
      (TRDs) in many NAC TFs. Using motif searches and interaction studies in yeast we
      identified an evolutionarily conserved sequence, the LP motif, in the TRD of
      HvNAC013. This motif was sufficient for transcriptional activity. In contrast,
      HvNAC005 did not function as a transcriptional activator suggesting that an
      involvement of HvNAC013 and HvNAC005 in senescence will be different. HvNAC013
      interacted with barley radical-induced cell death 1 (RCD1) via the very C
      terminal part of its TRD, outside of the region containing the LP motif. No
      significant secondary structure was induced in the HvNAC013 TRD upon interaction
      with RCD1. RCD1 also interacted with regions dominated by intrinsic disorder in
      TFs of the MYB and basic helix-loop-helix families. We propose that RCD1 is a
      regulatory protein capable of interacting with many different TFs by exploiting
      their intrinsic disorder. In addition, we present the first structural
      characterization of NAC C-terminal domains and relate intrinsic disorder and
      sequence motifs to activity and protein-protein interactions.

PMID- 21856751
TI  - Cotranscriptional association of mRNA export factor Yra1 with C-terminal domain
      of RNA polymerase II.
AB  - The unique C-terminal domain (CTD) of RNA polymerase II, composed of tandem
      heptad repeats of the consensus sequence YSPTSPS, is subject to differential
      phosphorylation throughout the transcription cycle. Several RNA processing
      factors have been shown to bind the phosphorylated CTD and use it to localize to
      nascent pre-mRNA during transcription. In Saccharomyces cerevisiae, the mRNA
      export protein Yra1 (ALY/RNA export factor in metazoa) cotranscriptionally
      associates with mRNA and delivers it to the nuclear pore complex for export to
      the cytoplasm. Here we report that Yra1 directly binds in vitro the
      hyperphosphorylated form of the CTD characteristic of elongating RNA polymerase
      II and contains a phospho-CTD-interacting domain within amino acids 18-184, which
      also include an "RNA recognition motif" (RRM) (residues 77-184). Using UV cross
      linking, we showed that the RRM alone binds RNA, although a larger segment
      extending to the C terminus (amino acids 77-226) displayed stronger RNA binding
      activity. Although the RRM is implicated in both RNA and CTD binding, RRM point
      mutations separated these two functions. Both functions are important in vivo as
      RNA binding-defective or CTD binding-defective versions of Yra1 engendered growth
      and mRNA export defects. We also report the construction and characterization of
      a useful new temperature-sensitive YRA1 allele (R107A/F126A). Using ChIP, we
      demonstrated that removing the N-terminal 76 amino acids of Yra1 (all of the
      phospho-CTD-interacting domain up to the RRM) results in a 10-fold decrease in
      Yra1 recruitment to genes during elongation. These results indicate that the
      phospho-CTD is likely involved directly in the cotranscriptional recruitment of
      Yra1.

PMID- 21856752
TI  - Ligand displaces heat shock protein 90 from overlapping binding sites within the
      aryl hydrocarbon receptor ligand-binding domain.
AB  - Hsp90 (heat shock protein of 90 kDa) is often found associated with functional
      domains of client proteins, including those for ligand binding, dimerization, DNA
      binding, and enzymatic activity. Although Hsp90 can maintain the conformation of
      functionally important domains prior to activation of the client protein, its
      specific binding site and the mechanism(s) of Hsp90 dissociation during
      activation are unknown. Here, we have identified and characterized residues
      involved in Hsp90 binding within the aryl hydrocarbon receptor (AhR) ligand
      binding domain and demonstrate that they overlap with those involved in ligand
      binding. In agreement with this spatial model, ligand binding results in Hsp90
      dissociation from the AhR Per-ARNT-Sim B fragment. Interestingly, whereas Hsp90
      binding residues within the ligand-binding domain were not involved in Hsp90
      dependent AhR protein stability, several of these residues are important for
      ligand-dependent AhR activation, and their mutation resulted in conversion of two
      AhR antagonists/partial agonists into full AhR agonists. These studies reveal co
      localization of a tentative Hsp90-binding site with that for AhR ligand binding
      and provide the first molecular mechanism for Hsp90 dissociation in the
      activation of a client protein.

PMID- 21856754
TI  - Effects of mesenchymal stem cells on matrix metalloproteinase synthesis in
      cardiac fibroblasts.
AB  - Mesenchymal stem cell (MSC) transplantation has been known to decrease matrix
      metalloproteinase (MMP) synthesis in myocardium after myocardial infarction (MI)
      and improve ventricular remodeling; however, the underlying mechanisms are
      unclear. This study investigated the effects of MSC on MMP synthesis in cardiac
      fibroblasts (CFs) through paracrine actions. CFs were cultured under hypoxic
      (0.5% pO(2)) conditions for 24 h before co-culture with MSCs or hypoxia
      preconditioned MSCs (H-MSCs) in transwell plates. CFs and MSCs/H-MSCs shared a
      medium with or without erythropoietin (EPO) neutralizing antibody (EPOAb) or EPO
      soluble receptor (EPOsR). The results showed that protein expression and activity
      of MMP-2 and membrane type 1-MMP, but not MMP-9, in CFs were significantly
      increased in response to hypoxia and decreased after co-culture with MSCs or H
      MSCs. Hypoxia up-regulated phosphorylation of extracellular signal-regulated
      kinase (ERK)1/2 of CFs which was down-regulated after CFs' co-culture with MSCs.
      Tissue inhibitors of metalloproteinases-1 (TIMP-1) in CFs was decreased after
      hypoxia and increased when co-cultured with MSCs or H-MSCs. Exogenous EPOAb or
      EPOsR partially inhibited MSCs' effect on MMP-2 expression and activity in CFs.
      The present findings suggested that MSCs influence MMP/TIMP expression in CFs via
      the ERK1/2 pathway and EPO acts as a key factor in the paracrine actions of MSCs.

PMID- 21856753
TI  - Identification of a cytochrome P4502E1/Bid/C1q-dependent axis mediating
      inflammation in adipose tissue after chronic ethanol feeding to mice.
AB  - Chronic, heavy alcohol exposure results in inflammation in adipose tissue,
      insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q
      dependent pathway that is activated in response to chronic ethanol and is
      required for the development of inflammation in adipose tissue. Ethanol feeding
      for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers
      of adipose tissue inflammation relative to pair-fed controls independent of
      increased body weight or adipocyte size. Ethanol feeding increased the expression
      of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and
      Cyp2e1(-/-) mice were protected from adipose tissue inflammation in response to
      ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in
      adipose tissue of wild-type mice but not in Cyp2e1(-/-) or Bid (-/-) mice.
      Apoptosis contributed to adipose inflammation, as the expression of multiple
      inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic
      pathway. The complement protein C1q binds to apoptotic cells, facilitating their
      clearance and activating complement. Making use of C1q-deficient mice, we found
      that activation of complement via C1q provided the critical link between
      CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in
      response to chronic ethanol. In summary, chronic ethanol increases CYP2E1
      activity in adipose, leading to Bid-mediated apoptosis and activation of
      complement via C1q, finally resulting in adipose tissue inflammation. Taken
      together, these data identify a novel mechanism for the development of adipose
      tissue inflammation that likely contributes to the pathophysiological effects of
      ethanol.

PMID- 21856755
TI  - Tumor necrosis factor-alpha induces epithelial-mesenchymal transition of renal
      cell carcinoma cells via a nuclear factor kappa B-independent mechanism.
AB  - Chronic low dose of tumor necrosis factor-alpha (TNF-alpha) stimulation promotes
      tumorigenesis by facilitating tumor proliferation and metastasis. The plasma
      levels of TNF-alpha are increased in patients with renal cell carcinoma (RCC).
      Furthermore, high-grade clear cell RCC cell lines secrete more TNF-alpha than low
      grade ones, and allow low-grade cell lines' gain of invasive ability. However,
      the molecular mechanism of TNF-alpha in mediating progression of RCC cells
      remains unclear. In the present study, TNF-alpha induced epithelial-mesenchymal
      transition (EMT) of RCC cells by repressing E-cadherin, promoting invasiveness
      and activating matrix metalloproteinase (MMP) 9 activity. RCC cells underwent
      promoted growth in vivo following stimulation with TNF-alpha. In addition, TNF
      alpha induced phosphorylation of extracellular signal-regulated kinase, nuclear
      factor kappa B (NF-kappaB) and Akt in a time-dependent manner, and increased
      nuclear translocation and promoter activity of NF-kappaB. To investigate the role
      of NF-kappaB activation in TNF-alpha-induced EMT of RCC, we employed chemical
      inhibitors (NF-kappaB activation inhibitor and Bay 11-7082) and transfected
      dominant-negative (pCMV-IkappaBalphaM) and overexpressive (pFLAG-p65) vectors of
      NF-kappaB. While overexpression of NF-kappaB p65 alone could induce E-cadherin
      loss in RCC, EMT phenotypes and MMP9 expressions induced by TNF-alpha were not
      reversed by the inhibitors of NF-kappaB activation. These results suggest that
      the TNF-alpha signaling pathway is involved in the tumorigenesis of RCC. However,
      NF-kappaB activation is not crucial for invasion and EMT enhanced by TNF-alpha in
      RCC cells.

PMID- 21856756
TI  - Chitosan oligosaccharide decreases very-low-density lipoprotein triglyceride and
      increases high-density lipoprotein cholesterol in high-fat-diet-fed rats.
AB  - It is well known that chitosan has beneficial lipid-regulating effects, but it
      remains unknown whether chitosan oligosaccharide (COS), the chitosan degradation
      product, has the same lipid benefits. High-fat-diet-fed Wistar rats were
      administrated with COS by gastric gavage for three weeks. The effects of COS on
      lipids, lipoprotein components and lipid metabolism related protein activities
      were investigated. Plasma lipids level assays by an enzyme method showed that COS
      decreased triglyceride (TG) by 29-31%, and increased high-density lipoprotein
      (HDL) cholesterol by 8-11%, but did not affect low-density lipoprotein (LDL)
      cholesterol. Lipid distribution analysis through fast protein liquid
      chromatography indicated that COS significantly decreased TG content distributed
      in very-low-density lipoprotein (VLDL)/LDL fractions but increased cholesterol
      content in HDL fractions. Apolipoprotein analysis through plasma
      ultracentrifugation and sodium dodecyl sulfate polyacrylamide gel electrophoresis
      displayed that COS decreased apolipoprotein B-100 of LDL and increased
      apolipoprotein E of LDL and apolipoprotein B-100 of VLDL, but did not change apoA
      I content of HDL particles. Lipoprotein formation associated protein
      determination showed that COS also increased plasma activity of lecithin
      cholesterol acyl transferase but not phospholipid transfer protein. The present
      study suggests that COS may play a beneficial role in plasma lipid regulation of
      rats with dyslipidemia induced by high-fat diet. The COS-decreased VLDL/LDL TG
      and -enhanced HDL cholesterol may be related to the upregulated activity of
      lecithin cholesterol acyl transferase.

PMID- 21856757
TI  - The modENCODE Data Coordination Center: lessons in harvesting comprehensive
      experimental details.
AB  - The model organism Encyclopedia of DNA Elements (modENCODE) project is a National
      Human Genome Research Institute (NHGRI) initiative designed to characterize the
      genomes of Drosophila melanogaster and Caenorhabditis elegans. A Data
      Coordination Center (DCC) was created to collect, store and catalog modENCODE
      data. An effective DCC must gather, organize and provide all primary, interpreted
      and analyzed data, and ensure the community is supplied with the knowledge of the
      experimental conditions, protocols and verification checks used to generate each
      primary data set. We present here the design principles of the modENCODE DCC, and
      describe the ramifications of collecting thorough and deep metadata for
      describing experiments, including the use of a wiki for capturing protocol and
      reagent information, and the BIR-TAB specification for linking biological samples
      to experimental results. modENCODE data can be found at http://www.modencode.org.

PMID- 21856758
TI  - Alanyl-glutamine dipeptide restores the cytoprotective stress proteome of
      mesothelial cells exposed to peritoneal dialysis fluids.
AB  - BACKGROUND: Exposure of mesothelial cells to peritoneal dialysis fluids (PDF)
      results in cytoprotective cellular stress responses (CSR) that counteract PDF
      induced damage. In this study, we tested the hypothesis that the CSR may be
      inadequate in relevant models of peritoneal dialysis (PD) due to insufficient
      levels of glutamine, resulting in increased vulnerability against PDF
      cytotoxicity. We particularly investigated the role of alanyl-glutamine (Ala-Gln)
      dipeptide on the cytoprotective PDF stress proteome. METHODS: Adequacy of CSR was
      investigated in two human in vitro models (immortalized cell line MeT-5A and
      mesothelial cells derived from peritoneal effluent of uraemic patients) following
      exposure to heat-sterilized glucose-based PDF (PD4-Dianeal, Baxter) diluted with
      medium and, in a comparative proteomics approach, at different levels of
      glutamine ranging from depletion (0 mM) via physiological (0.7 mM) to
      pharmacological levels (8 mM administered as Ala-Gln). RESULTS: Despite severe
      cellular injury, expression of cytoprotective proteins was dampened upon PDF
      exposure at physiological glutamine levels, indicating an inadequate CSR.
      Depletion of glutamine aggravated cell injury and further reduced the CSR,
      whereas addition of Ala-Gln at pharmacological level restored an adequate CSR,
      decreasing cellular damage in both PDF exposure systems. Ala-Gln specifically
      stimulated chaperoning activity, and cytoprotective processes were markedly
      enhanced in the PDF stress proteome. CONCLUSIONS: Taken together, this study
      demonstrates an inadequate CSR of mesothelial cells following PDF exposure
      associated with low and physiological levels of glutamine, indicating a new and
      potentially relevant pathomechanism. Supplementation of PDF with pharmacological
      doses of Ala-Gln restored the cytoprotective stress proteome, resulting in
      improved resistance of mesothelial cells to exposure to PDF. Future work will
      study the clinical relevance of CSR-mediated cytoprotection.

PMID- 21856759
TI  - BOLD imaging: a potential predictive biomarker of renal functional outcome
      following revascularization in atheromatous renovascular disease.
AB  - BACKGROUND: Stenting of the stenosed renal artery is commonly employed in
      atheromatous renovascular disease (ARVD) in order to revascularize the affected
      kidney. However, it is still far from clear which patient subgroups should be
      revascularized as stenting carries small but significant risks. We have
      previously demonstrated that the ratio of magnetic resonance-measured renal
      volume to isotopic single kidney glomerular filtration rate (isoSK-GFR) is higher
      in kidneys which show functional improvement after revascularization. Blood
      oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) does not require
      contrast administration and is sensitive to changes in tissue concentration of
      deoxyhaemoglobin. METHODS: In this study, we test the hypothesis that baseline
      BOLD R2* map signal and R2*:isoSK-GFR ratio will provide an additional
      independent predictive biomarker of response to revascularization. RESULTS:
      Studies were performed in 28 subjects (16 ARVD and 12 controls). All subjects had
      R2* mapping and isoSK-GFR measured at baseline and at 4-month follow-up. MRI data
      were collected on a 3 T whole-body MRI scanner using a coronal dual-echo, 2D
      gradient-echo breath-hold acquisition. Parenchymal regions of interest (ROIs)
      were drawn on a representative slice through the middle of the kidney. Parametric
      maps of R2* were generated and mean values of R2* were calculated for every ROI.
      The ratio of R2*:isoSK-GFR at baseline was significantly greater in kidneys where
      renal function improved (5.91 +/- 6.51) versus stable (1.78 +/- 1.11),
      deteriorated (2.15 +/- 1.79) or controls (1.5 +/- 0.91), P = 0.003. R2*:isoSK-GFR
      ratio that was greater than 95% confidence interval of the control kidneys was
      66.7% sensitive, but 85.7% specific in predicting a positive renal functional
      outcome. CONCLUSIONS: These pilot data show that BOLD R2* imaging, presumably by
      detecting intra-renal deoxyhaemoglobin in still viable 'hibernating' parenchyma,
      coupled with isoSK-GFR may provide an effective predictive biomarker for positive
      renal functional response to revascularization. R2* imaging is non-invasive,
      quick to perform and could provide further insight into reversible parenchymal
      changes in ARVD kidneys.

PMID- 21856761
TI  - Fluid overload at initiation of renal replacement therapy is associated with lack
      of renal recovery in patients with acute kidney injury.
AB  - BACKGROUND: Patients with acute kidney injury (AKI) requiring initiation of renal
      replacement therapy (RRT) have poor short- and long-term outcomes, including the
      development of dialysis dependence. Currently, little is known about what factors
      may predict renal recovery in this population. METHODS: We conducted a single
      center, retrospective analysis of 170 hospitalized adult patients with AKI
      attributed to acute tubular necrosis who required inpatient initiation of RRT.
      Data collection included patient characteristics, laboratory data, details of
      hospital course and degree of fluid overload at RRT initiation. The primary
      outcome was recovery of renal function to dialysis independence. RESULTS: Within
      1 year of RRT initiation, 35.9% (61/170) of patients reached the primary end
      point of renal recovery. The median (interquartile range) duration of RRT was 11
      (3-33) days and 83.6% (51/61) recovered prior to hospital discharge. Recovering
      patients had significantly less fluid overload at the time of RRT initiation
      compared to non-recovering patients (3.5 versus 9.3%, P = 0.004). In multivariate
      Cox proportional hazard regression analysis, a rise in percent fluid overload at
      dialysis initiation remained a significant negative predictor of renal recovery
      (hazard ratio 0.97, 95% confidence interval 0.95-1.00, P = 0.024). CONCLUSIONS:
      In patients with AKI, a higher degree of fluid overload at RRT initiation
      predicts worse renal recovery at 1 year. Clinical trials are needed to determine
      whether interventions targeting fluid overload may improve patient and renal
      outcomes.

PMID- 21856760
TI  - High levels of oxidized LDL in circulating immune complexes are associated with
      increased odds of developing abnormal albuminuria in Type 1 diabetes.
AB  - BACKGROUND: Modified low-density lipoprotein (LDL) immune complexes (IC) have
      proinflammatory properties and play a role in albuminuria development. METHODS:
      We measured oxidized LDL (oxLDL) and advanced glycation end-product (AGE)-LDL in
      IC isolated from sera of Type 1 diabetic subjects followed for 14-20 years and
      studied their association with abnormal albuminuria. Patients with albumin
      excretion rates (AER)<40 mg/24 h at baseline and follow-up (n=302) were deemed
      resistant to developing abnormal albuminuria. Patients with AER<40 mg/24 h at
      baseline whose AER levels progressed to >40 mg/24 h were considered prone to
      abnormal albuminuria (n=185), those who progress to AER>299 mg/24 h were
      considered as having macroalbuminuria (n=57). The odds of developing abnormal
      albuminuria were estimated by logistic regression based on natural log
      transformed levels of oxLDL and AGE-LDL in IC and stratified by baseline AER
      decile. RESULTS: OxLDL and AGE-LDL were significantly higher in IC isolated from
      patients progressing to abnormal albuminuria. In unadjusted conditional logistic
      analysis, an increase of 1 SD in oxLDL and AGE-LDL levels in IC significantly
      increased the odds ratio (OR) for development of macroalbuminuria, respectively,
      by a factor of 2.5 and 1.8 (P<0.001, P=0.008). The increased odds of developing
      macroalbuminuria remained significant when adjusted for treatment group, diabetes
      duration, retinopathy, baseline hemoglobin A1c and LDL (OR=2.5 and 1.8,
      respectively, P<0.01). CONCLUSION: Higher levels of oxLDL and AGE-LDL in
      circulating IC were associated with increased odds to develop abnormal
      albuminuria.

PMID- 21856763
TI  - The relationship of maternal and child illness uncertainty to child depressive
      symptomotology: a mediational model.
AB  - OBJECTIVE: To examine the relationship of parent and child ratings of illness
      uncertainty to depressive symptomotology in children with a chronic illness using
      a mediational model framework. METHOD: Mother-child dyads (N = 103 pairs) each
      completed measures of perceived illness uncertainty, while youth also completed a
      measure of depressive symptomotology. RESULTS: Maternal uncertainty was directly
      related to child depressive symptoms; however, this relationship was mediated by
      child uncertainty. CONCLUSION: It would appear that a key mechanism by which
      parent-related uncertainty influences child depressive symptoms is through child
      uncertainty, underscoring the importance of examining cognitive appraisal
      variables and means of transmission in parent-child interactions.

PMID- 21856762
TI  - Protective actions of nebivolol on chronic nitric oxide synthase inhibition
      induced hypertension and chronic kidney disease in the rat: a comparison with
      angiotensin II receptor blockade.
AB  - BACKGROUND: Nitric oxide (NO) deficiency contributes to chronic kidney disease
      (CKD) progression and hypertension. The beta-blocker, nebivolol (N), also
      enhances NO production, and we studied whether N attenuates CKD and hypertension
      caused by chronic NO synthase inhibition (CNOSI). METHODS: Male Sprague-Dawley
      rats on 6 weeks of CNOSI (L-NAME, 150 mg/L drinking water) received placebo (P),
      N (10 mg/kg/day), olmesartan (O, 2.5 mg/kg/day) or N + O. Blood pressure (BP) and
      urine protein and NOx (metabolites of NO) were monitored throughout. We measured
      glomerular sclerosis (GS), creatinine clearance (C(Cr)) and components of the NO
      and oxidant pathways in the renal cortex. RESULTS: BP increased >50 mmHg in P by
      weeks 4-6, but no change occurred in N, O or N + O. P rats developed proteinuria
      and GS and C(Cr) was ~30% of normal. In N, O and N + O, all values remained
      normal. In renal cortex of P, p22phox and nitrotyrosine abundance as well as
      H(2)O(2) levels were higher and extracellular superoxide dismutase (EC SOD) was
      lower versus normal kidneys. N, O and N + O normalized p22phox, H(2)O(2) and EC
      SOD and increased Mn SOD above normal. The cortical neuronal NO synthase (nNOS)
      beta abundance increased in P and this was prevented by N, O and N + O.
      CONCLUSION: We suggest that the major benefit from both N and O is reduction in
      oxidative stress in the renal cortex, which may potentiate residual local NO.
      There was no additive benefit of N + O since each drug effectively prevented
      injury, but a combination may be beneficial where protection is incomplete with
      each drug. The increased nNOSbeta protein seen early in the course of the CKD may
      contribute to the evolving GS.

PMID- 21856764
TI  - Integrate health services for refugees into national healthcare, says UN report.

PMID- 21856765
TI  - International donations to global fight against AIDS fall for first time.

PMID- 21856766
TI  - Disease flare after tyrosine kinase inhibitor discontinuation in patients with
      EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib:
      implications for clinical trial design.
AB  - PURPOSE: Treatment of patients with oncogene-addicted cancers with tyrosine
      kinase inhibitors (TKI) is biologically and clinically different than with
      cytotoxic chemotherapy. We have observed that some patients with EGFR-mutant lung
      cancer and acquired resistance to erlotinib or gefitinib (RECIST progression
      after initial benefit) have accelerated progression of disease after
      discontinuation of TKI. To examine this observation and define the course of
      patients following TKI discontinuation, we systematically evaluated patients
      enrolled on clinical trials of agents to treat acquired resistance to erlotinib
      or gefitinib. METHODS: We evaluated patients with EGFR-mutant lung cancer who
      participated in trials for patients with acquired resistance that mandated TKI
      discontinuation before administration of study therapy. Disease flare was defined
      as hospitalization or death attributable to disease progression during the
      washout period. RESULTS: Fourteen of 61 patients (23%; 95% CI: 14-35) experienced
      a disease flare. The median time to disease flare after TKI discontinuation was 8
      days (range 3-21). Factors associated with disease flare included shorter time to
      progression on initial TKI (P = 0.002) and the presence of pleural (P = 0.03) or
      CNS disease (P = 0.01). There was no association between disease flare and the
      presence of T790M at the time of acquired resistance. CONCLUSIONS: In patients
      with EGFR-mutant lung cancer and acquired resistance to epidermal growth factor
      receptor TKIs, discontinuation of erlotinib or gefitinib before initiation of
      study treatment is associated with a clinically significant risk of accelerated
      disease progression. Clinical trials in this patient population must minimize
      protocol-mandated washout periods.

PMID- 21856767
TI  - A gene expression-based predictor for myeloma patients at high risk of developing
      bone disease on bisphosphonate treatment.
AB  - PURPOSE: Myeloma bone disease impairs quality of life and is associated with
      impaired survival. Even with effective bisphosphonate treatment, a significant
      proportion of patients still develop skeletal-related events (SRE). Identifying
      such patients at presentation would allow treatment modification. EXPERIMENTAL
      DESIGN: To investigate the molecular basis of bone disease at presentation and to
      develop a predictive signature for patients at high risk of developing SREs on
      bisphosphonates, 261 presenting myeloma samples were analyzed by global gene
      expression profiling. The derived "SRE gene signature" was complemented by the
      integration of associated clinical parameters to generate an optimal predictor.
      RESULTS: Fifty genes were significantly associated with presenting bone disease,
      including the WNT signaling antagonist DKK1 and genes involved in growth factor
      signaling and apoptosis. Higher serum calcium level and the presence of bone
      disease and hyperdiploidy at presentation were associated with high risk of SRE
      development. A gene signature derived from the fourteen genes overexpressed in
      the SRE group was able to identify patients at high risk of developing an SRE on
      treatment. These genes either belonged to the IFN-induced family or were involved
      in cell signaling and mitosis. Multivariate logistic model selection yielded an
      optimal SRE predictor comprising seven genes and calcium level, which was
      validated as an effective predictor in a further set of patients. CONCLUSIONS:
      The simple expression-based SRE predictor can effectively identify individuals at
      high risk of developing bone disease while being on bisphosphonates. This
      predictor could assist with developing future trials on novel therapies aimed at
      reducing myeloma bone disease.

PMID- 21856768
TI  - Significant biological role of sp1 transactivation in multiple myeloma.
AB  - PURPOSE: The transcription factor specificity protein 1 (Sp1) controls number of
      cellular processes by regulating the expression of critical cell cycle,
      differentiation, and apoptosis-related genes containing proximal GC/GT-rich
      promoter elements. We here provide experimental and clinical evidence that Sp1
      plays an important regulatory role in multiple myeloma (MM) cell growth and
      survival. EXPERIMENTAL DESIGN: We have investigated the functional Sp1 activity
      in MM cells using a plasmid with Firefly luciferase reporter gene driven by Sp1
      responsive promoter. We have also used both siRNA- and short hairpin RNA-mediated
      Sp1 knockdown to investigate the growth and survival effects of Sp1 on MM cells
      and further investigated the anti-MM activity of terameprocol (TMP), a small
      molecule that specifically competes with Sp1-DNA binding in vitro and in vivo.
      RESULTS: We have confirmed high Sp1 activity in MM cells that is further induced
      by adhesion to bone marrow stromal cells (BMSC). Sp1 knockdown decreases MM cell
      proliferation and induces apoptosis. Sp1-DNA binding inhibition by TMP inhibits
      MM cell growth both in vitro and in vivo, inducing caspase-9-dependent apoptosis
      and overcoming the protective effects of BMSCs. CONCLUSIONS: Our results show Sp1
      as an important transcription factor in myeloma that can be therapeutically
      targeted for clinical application by TMP.

PMID- 21856769
TI  - Targeting ALDH(bright) human carcinoma-initiating cells with ALDH1A1-specific
      CD8+ T cells.
AB  - PURPOSE: Cancer-initiating cells (CIC) are considered to represent the
      subpopulation of tumor cells that is resistant to conventional cancer treatments,
      highly tumorigenic in immunodeficient mice, and responsible for tumor recurrence
      and metastasis. Based on an elevated aldehyde dehydrogenase (ALDH) activity
      attributable to ALDH1/3 isoforms, ALDH(bright) cells have been identified and
      isolated from tumors and shown to have characteristics of CIC. The ALDH1A1
      isoform was previously identified as a tumor antigen recognized by CD8(+) T
      cells. This study examines the ability of ALDH1A1-specific CD8(+) T cells to
      eliminate ALDH(bright) cells and control tumor growth and metastases.
      EXPERIMENTAL DESIGN: ALDH(bright) cells were isolated by flow cytometry using
      ALDEFLUOR from HLA-A2(+) human head and neck, breast, and pancreas carcinoma cell
      lines and tested for their tumorigenicity in immunodeficient mice. ALDH1A1
      specific CD8(+) T cells were generated in vitro and tested for their ability to
      eliminate CICs in vitro and in vivo by adoptive transfer to immunodeficient mice
      bearing human tumor xenografts. RESULTS: ALDH(bright) cells isolated by flow
      cytometry from HLA-A2(+) breast, head and neck, and pancreas carcinoma cell lines
      at low numbers (500 cells) were tumorigenic in immunodeficient mice. ALDH(bright)
      cells present in these cell lines, xenografts, or surgically removed lesions were
      recognized by ALDH1A1-specific CD8(+) T cells in vitro. Adoptive therapy with
      ALDH1A1-specific CD8(+) T cells eliminated ALDH(bright) cells, inhibited tumor
      growth and metastases, or prolonged survival of xenograft-bearing immunodeficient
      mice. CONCLUSIONS: The results of this translational study strongly support the
      potential of ALDH1A1-based immunotherapy to selectively target CICs in human
      cancer.

PMID- 21856770
TI  - Recombinant human erythropoietin in combination with chemotherapy increases
      breast cancer metastasis in preclinical mouse models.
AB  - PURPOSE: Erythropoiesis-stimulating agents (ESA) are used clinically for treating
      cancer-related anemia. Recent clinical trials have reported increased adverse
      events and reduced survival in ESA-treated breast cancer patients receiving
      chemotherapy, potentially related to erythropoietin (EPO)-induced cancer
      progression. However, minimal preclinical data are available about the impact of
      EPO on metastatic cell behavior and/or the metastatic process, and this was the
      goal of our study. EXPERIMENTAL DESIGN: Breast cancer cell lines were treated
      with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors
      (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in
      vitro (two-dimensional/three-dimensional growth and survival) and in vivo
      (tumorigenicity and metastasis), in the presence or absence of EPO and/or
      cytotoxic agents. RESULTS: A large variation in EPOR expression across cell lines
      was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA
      MB-435 cells (P < 0.05); however, rHuEPO treatment alone or combined with
      chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO
      increased lung metastases in immunocompromised mice injected with MDA-MB-231 or
      MDA-MB-435 cells and treated with chemotherapy relative to mice treated with
      chemotherapy alone (P < 0.05). CONCLUSIONS: The lack of an in vitro effect of
      rHuEPO highlights the importance of in vivo studies to delineate the effects of
      EPO on the metastatic process. These studies may begin to uncover the underlying
      functional explanation for the observed EPO-related adverse events and decreased
      survival in ESA-treated metastatic breast cancer patients undergoing
      chemotherapy.

PMID- 21856771
TI  - Therapeutic effect of lenalidomide in a novel xenograft mouse model of human
      blastic NK cell lymphoma/blastic plasmacytoid dendritic cell neoplasm.
AB  - PURPOSE: Blastic natural killer (NK) cell lymphoma/blastic plasmacytoid dendritic
      cell neoplasm (BNKL) is a rare and aggressive neoplasia characterized by
      infiltration of blast CD4(+)/CD56(+) cells in the skin, the bone marrow, and
      peripheral blood. Currently, more efforts are required to better define molecular
      and biological mechanisms associated with this pathology. To the best of our
      knowledge, no mouse model recapitulated human BNKL so far. EXPERIMENTAL DESIGN:
      Primary bone marrow cells from a BNKL patient were injected in nonobese
      diabetes/severe combined immunodeficient interleukin (IL) 2rgamma(-/-) mice with
      the intent to generate the first BNKL orthotopic mouse model. Moreover, because
      of the lack of efficient treatments for BNKL, we treated mice with lenalidomide,
      an immunomodulatory and antiangiogenic drug. RESULTS: We generated in mice a
      fatal disease resembling human BNKL. After lenalidomide treatment, we observed a
      significant reduction in the number of peripheral blood, bone marrow, and spleen
      BNKL cells. Tumor reduction parallels with a significant decrease in the number
      of circulating endothelial and progenitor cells and CD31(+) murine endothelial
      cells. In mice treated with lenalidomide, BNKL levels of active caspase-3 were
      significantly augmented, thus showing proapoptotic and cytotoxic effects of this
      drug in vivo. An opposite result was found for proliferating cell nuclear
      antigen, a proliferation marker. CONCLUSIONS: Our BNKL model might better define
      the cellular and molecular mechanisms involved in this disease, and lenalidomide
      might be considered for the future therapy of BNKL patients.

PMID- 21856772
TI  - Arrhythmia type after persistent atrial fibrillation ablation predicts success of
      the repeat procedure.
AB  - BACKGROUND: The aim of the study was to investigate whether the type of
      arrhythmia recurrence after ablation of persistent atrial fibrillation (AF) has
      an impact on the maintenance of sinus rhythm after the repeat ablation procedure.
      METHODS AND RESULTS: Included were 78 consecutive patients (82% men; mean age,
      61+/-10 years; mean left atrial diameter, 47+/-4 mm) with persistent AF who
      underwent >=1 repeat ablation. The initial ablation procedure had consisted of
      pulmonary vein isolation with additional substrate modification (ablation of
      complex fractionated atrial electrograms [n=63] or linear lesions [n=15]).
      Patients presented for reablation either with persistent atrial tachycardia (AT)
      (group 1, n=36), persistent AF (group 2, n=37), or paroxysmal AF (group 3, n=5).
      The primary end point was freedom from any arrhythmia off antiarrhythmic drugs 6
      and 9 months after the reablation procedure. Estimated proportions of patients
      reaching the primary end point were 59% for group 1, 28% for group 2, and 100%
      for group 3 at 6 months and 51%, 23%, and 100%, for groups 1, 2, and 3,
      respectively, at 9 months (P=0.002). CONCLUSIONS: In patients presenting for a
      repeat procedure after ablation of persistent AF, the occurrence of AT is
      associated with a significantly better outcome compared with recurrent persistent
      AF. These results suggest that AT might be considered as a step toward sinus
      rhythm.

PMID- 21856773
TI  - Resveratrol inhibits proliferation and survival of Epstein Barr virus-infected
      Burkitt's lymphoma cells depending on viral latency program.
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenolic natural product,
      shows chemopreventive properties against several cancers, heart diseases,
      inflammation, and viral infections. Epstein Barr virus (EBV), a gamma
      herpesvirus, contributes to the development of several human cancers including
      Burkitt's lymphoma (BL). In this study, we asked whether treatment with
      resveratrol would affect the viability of EBV-positive BL cells displaying
      different forms of latency. We report here that resveratrol, regardless of EBV
      status, induces caspase-dependent apoptosis by arresting cell-cycle progression
      in G(1) phase. However, resveratrol strongly induced apoptosis in EBV(-) and
      latency I EBV(+) cells, whereas latency II and latency III EBV(+) BL cells showed
      a survival advantage that increased with the extent of the pattern of viral gene
      expression. Resveratrol-induced cell-cycle arrest and apoptosis occurred in
      association with induction of p38 MAPK phosphorylation and suppression of ERK1/2
      signaling pathway. Moreover, NF-kappaB DNA-binding activity was inhibited in all
      BL lines except EBV(+) latency III cells. LMP1 oncogene, which is expressed in
      latency III phenotype, is involved with the higher resistance to the
      antiproliferative effect of resveratrol because siRNA-mediated inhibition of LMP1
      greatly increased the sensitivity of latency III BL cells as well as that of
      lymphoblastoid cell lines to the polyphenol. We propose that a combined
      resveratrol/siRNA strategy may be a novel approach for the treatment of EBV
      associated B-cell malignancies in which the viral pattern of gene expression has
      been defined.

PMID- 21856774
TI  - Effect of the inositol polyphosphate InsP(6) on DNA-PK-dependent phosphorylation.
AB  - Inositol hexakisphosphate (InsP(6)) is a member of the inositol polyphosphate
      group that participates in numerous intracellular signaling pathways. Cheung and
      colleagues previously reported that InsP(6) stimulated double-strand break repair
      by nonhomologous end joining (NHEJ) in cell-free extracts and that InsP(6)
      binding by the Ku70/80 subunit of the DNA-dependent protein kinase (DNA-PK) was
      required for stimulation of NHEJ in vitro. This report describes InsP(6)
      dependent phosphorylation of two NHEJ factors, XRCC4 and XLF, in partially
      purified human cell extracts. XRCC4 and XLF are known substrates for DNA-PK,
      which does not require InsP(6) for protein kinase activity. Consistent with a
      role for DNA-PK in these reactions, InsP(6)-dependent phosphorylation of XRCC4
      and XLF was DNA dependent and not observed in the presence of DNA-PK inhibitors.
      Depletion of the Ku70/80 DNA-, InsP(6)-binding subunit of DNA-PK resulted in loss
      of InsP(6)-dependent phosphorylation and showed a requirement for Ku70/80 in
      these reactions. Complementation of Ku70/80-depleted reactions with recombinant
      wild-type Ku70/80 restored InsP(6)-dependent phosphorylation of XRCC4 and XLF. In
      contrast, addition of a Ku70/80 mutant with reduced InsP(6) binding failed to
      restore InsP(6)-dependent phosphorylation. While additional protein kinases may
      participate in InsP(6)-dependent phosphorylation of XRCC4 and XLF, data presented
      here describe a clear requirement for DNA-PK in these phosphorylation events.
      Furthermore, these data suggest that binding of the inositol polyphosphate
      InsP(6) by Ku70/80 may modulate the substrate specificity of the phosphoinositide
      3-kinase-related protein kinase DNA-PK.

PMID- 21856775
TI  - MT1-MMP cooperates with Kras(G12D) to promote pancreatic fibrosis through
      increased TGF-beta signaling.
AB  - Pancreatic cancer is associated with a pronounced fibrotic reaction that was
      recently shown to limit delivery of chemotherapy. To identify potential
      therapeutic targets to overcome this fibrosis, we examined the interplay between
      fibrosis and the key proteinase membrane type 1-matrix metalloproteinase (MT1
      MMP, MMP-14), which is required for growth and invasion in the collagen-rich
      microenvironment. In this article, we show that compared with control mice
      (Kras(+)/MT1-MMP(-)) that express an activating Kras(G12D) mutation necessary for
      pancreatic cancer development, littermate mice that express both MT1-MMP and
      Kras(G12D) (Kras(+)/MT1-MMP(+)) developed a greater number of large, dysplastic
      mucin-containing papillary lesions. These lesions were associated with a
      significant amount of surrounding fibrosis, increased alpha-smooth muscle actin
      (+) cells in the stroma, indicative of activated myofibroblasts, and increased
      Smad2 phosphorylation. To further understand how MT1-MMP promotes fibrosis, we
      established an in vitro model to examine the effect of expressing MT1-MMP in
      pancreatic ductal adenocarcinoma (PDAC) cells on stellate cell collagen
      deposition. Conditioned media from MT1-MMP-expressing PDAC cells grown in three
      dimensional collagen enhanced Smad2 nuclear translocation, promoted Smad2
      phosphorylation, and increased collagen production by stellate cells. Inhibiting
      the activity or expression of the TGF-beta type I receptor in stellate cells
      attenuated MT1-MMP conditioned medium-induced collagen expression by stellate
      cells. In addition, a function-blocking anti-TGF-beta antibody also inhibited MT1
      MMP conditioned medium-induced collagen expression in stellate cells. Overall, we
      show that the bona fide collagenase MT1-MMP paradoxically contributes to fibrosis
      by increasing TGF-beta signaling and that targeting MT1-MMP may thus help to
      mitigate fibrosis.

PMID- 21856776
TI  - A novel mechanism for the transcriptional regulation of Wnt signaling in
      development.
AB  - Axial patterning of the embryonic brain requires a precise balance between
      canonical Wnt signaling, which dorsalizes the nervous system, and Sonic hedgehog
      (Shh), which ventralizes it. The ventral anterior homeobox (Vax) transcription
      factors are induced by Shh and ventralize the forebrain through a mechanism that
      is poorly understood. We therefore sought to delineate direct Vax target genes.
      Among these, we identify an extraordinarily conserved intronic region within the
      gene encoding Tcf7l2, a key mediator of canonical Wnt signaling. This region
      functions as a Vax2-activated internal promoter that drives the expression of
      dnTcf7l2, a truncated Tcf7l2 isoform that cannot bind beta-catenin and that
      therefore acts as a potent dominant-negative Wnt antagonist. Vax2 concomitantly
      activates the expression of additional Wnt antagonists that cooperate with
      dnTcf7l2. Specific elimination of dnTcf7l2 in Xenopus results in headless
      embryos, a phenotype consistent with a fundamental role for this regulator in
      forebrain development.

PMID- 21856778
TI  - Prospective randomized observer-blinded study comparing the analgesic efficacy of
      ultrasound-guided rectus sheath block and local anaesthetic infiltration for
      umbilical hernia repair.
AB  - BACKGROUND: Umbilical hernia repair, a common day-surgery procedure in children,
      is associated with considerable postoperative discomfort. Possible modes of
      postoperative analgesia for umbilical hernia repair are rectus sheath block (RSB)
      and local anaesthetic infiltration of the surgical site (LAI). METHODS: We
      undertook an observer-blinded, randomized, prospective, observational study to
      compare the efficacy of ultrasound-guided RSB and LAI in providing postoperative
      analgesia for umbilical hernia repair. Our primary objective was to compare the
      use of opioid medication between patients who receive RSB and those who receive
      LAI. Our secondary objectives were to compare the duration of analgesia based on
      time to first rescue analgesic, to compare the quality of analgesia based on
      revised FACES scale, and to determine the incidence of side-effects. RESULTS:
      Fifty-two patients (26 in each group) completed the study. There was a
      statistically significant difference in the perioperative opioid medication
      consumption between the LAI group [mean: 0.13 mg kg(-1), confidence interval
      (0.09-0.17 mg kg-1)] and the RSB group [mean: 0.07 mg kg-1, confidence interval
      (0.05-0.09 mg kg-1)] (P=0.008). When we compared the postoperative opioid
      consumption between the LAI group [mean: 0.1 mg kg-1, 95% confidence interval
      (0.07-0.13 mg kg-1)] and the RSB group [mean: 0.07 mg kg(-1), 95% confidence
      interval (0.05-0.09 mg kg-1)] (P=0.09), there was a trend towards statistical
      significance between the two groups. The difference in time to rescue analgesic
      administration between the RSB group [49.7 (36.9) min] and the LAI group [32.4
      (29.4) min] was not statistically significant (P=0.11). CONCLUSIONS: This study
      demonstrates that ultrasound-guided RSB provides superior analgesia in the
      perioperative period compared with infiltration of the surgical site after
      umbilical hernia repair. In comparing only the postoperative period, analgesia
      provided by an ultrasound-guided RSB showed a trend towards statistically
      significant improvement compared with infiltration of the surgical site.

PMID- 21856777
TI  - mir-11 limits the proapoptotic function of its host gene, dE2f1.
AB  - The E2F family of transcription factors regulates the expression of both genes
      associated with cell proliferation and genes that regulate cell death. The net
      outcome is dependent on cellular context and tissue environment. The mir-11 gene
      is located in the last intron of the Drosophila E2F1 homolog gene dE2f1, and its
      expression parallels that of dE2f1. Here, we investigated the role of miR-11 and
      found that miR-11 specifically modulated the proapoptotic function of its host
      gene, dE2f1. A mir-11 mutant was highly sensitive to dE2F1-dependent, DNA damage
      induced apoptosis. Consistently, coexpression of miR-11 in transgenic animals
      suppressed dE2F1-induced apoptosis in multiple tissues, while exerting no effect
      on dE2F1-driven cell proliferation. Importantly, miR-11 repressed the expression
      of the proapoptotic genes reaper (rpr) and head involution defective (hid), which
      are directly regulated by dE2F1 upon DNA damage. In addition to rpr and hid, we
      identified a novel set of cell death genes that was also directly regulated by
      dE2F1 and miR-11. Thus, our data support a model in which the coexpression of miR
      11 limits the proapoptotic function of its host gene, dE2f1, upon DNA damage by
      directly modulating a dE2F1-dependent apoptotic transcriptional program.

PMID- 21856779
TI  - Issues of justice.

PMID- 21856780
TI  - Living with idiopathic pulmonary fibrosis: an in-depth qualitative survey of
      European patients.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung
      disease of unknown origin. Despite recent advancements, the diagnosis and
      management of IPF remains a distinct clinical challenge; as a result, patients
      often experience considerable delays in receiving an accurate diagnosis and
      confusion regarding prognosis and the availability of treatment options. In order
      to gain further insights regarding patients' perspectives on the diagnostic
      process, disease education, emotional well-being, and quality of life, we
      conducted a qualitative in-depth survey among IPF patients in Europe. Patients
      with a physician-confirmed IPF diagnosis were recruited to participate in an in
      depth interview conducted by a trained facilitator who used a qualitative topic
      guide. A total of 45 patients from 5 European countries participated in the
      survey. The median reported time from initial presentation to confirmed diagnosis
      of IPF was 1.5 years (range <1 week to 12 years); in 58% of cases there was a
      delay of >1 year between initial presentation and a confirmed diagnosis of IPF.
      Additionally, 55% of patients reported consulting >=3 physicians before receiving
      an IPF diagnosis. Patient satisfaction with medical care and disease education
      appeared to be higher among patients who were receiving care at a recognized
      center of excellence. Patients generally had reasonable expectations regarding
      the goals of therapy, with most recognizing the irreversibility of the disease
      and the limited prospects for achieving a cure. The most common unmet needs cited
      by participants were disease education resources, access to centers of
      excellence, and familial support programs. Our findings suggest that patients
      with IPF commonly experience protracted delays in receiving an accurate diagnosis
      and generally perceive the level of medical care as suboptimal, despite
      expressing reasonable expectations regarding the goals of therapy. These results
      support the need for further improvement in the areas of diagnosis, disease
      management, and patient education.

PMID- 21856781
TI  - Monomeric C-reactive protein modulates classic complement activation on necrotic
      cells.
AB  - The acute-phase protein C-reactive protein (CRP) recruits C1q to the surface of
      damaged cells and thereby initiates complement activation. However, CRP also
      recruits complement inhibitors, such as C4b-binding protein (C4bp) and factor H,
      which both block complement progression at the level of C3 and inhibits
      inflammation. To define how CRP modulates the classic complement pathway, we
      studied the interaction of CRP with the classic pathway inhibitor C4bp. Monomeric
      CRP (mCRP), but not pentameric CRP (pCRP), binds C4bp and enhances degradation of
      C4b and C3b. Both C1q, the initiator, and C4bp, the inhibitor of the classic
      pathway, compete for mCRP binding, and this competition adjusts the local balance
      of activation and inhibition. After attachment of pCRP to the surface of necrotic
      rat myocytes, generation of mCRP was demonstrated over a period of 18 h.
      Similarly, a biological role for mCRP, C1q, and C4bp in the disease setting of
      acute myocardial infarction was revealed. In this inflamed tissue, mCRP, pCRP,
      C4bp, C1q, and C4d were detected in acetone-fixed and in unfixed tissue. Protein
      levels were enhanced 6 h to 5 d after infarction. Thus, mCRP bound to damaged
      cardiomyocytes recruits C1q to activate and also C4bp to control the classic
      complement pathway.

PMID- 21856782
TI  - MYCN and MYC regulate tumor proliferation and tumorigenesis directly through BMI1
      in human neuroblastomas.
AB  - The BMI1 gene is overexpressed in ~ 90% of human neuroblastomas. However, little
      is known about the regulation of BMI1 expression. Using microarray and
      immunohistochemical analysis, we show that BMI1 expression correlated with MYCN
      levels in MYCN-amplified human neuroblastomas, and with MYC levels in the MYCN
      nonamplified group. We further demonstrated that BMI1 is a direct target gene of
      MYCN/MYC in 3 neuroblastoma cell lines: BE (2)-C, LAN1, and SH-SY5Y.
      Overexpression of MYCN or MYC transactivated the BMI1 promoter and up-regulated
      BMI1 gene expression. shRNA-mediated knockdown of MYCN or MYC decreased BMI1 gene
      expression. Chromatin immunoprecipitation and point-mutation assays revealed that
      both MYCN and MYC bind to the E-box within the BMI1 promoter. Overexpression of
      BMI1, MYCN, and MYC independently increased both cell proliferation and tumor
      growth. Conversely, specific inhibition of BMI1, MYCN, and MYC decreased tumor
      cell proliferation and tumor growth. Interestingly, BMI1 suppression in MYCN/MYC
      overexpressing cells resulted in significantly greater inhibition compared to
      that in mock-transduced and parental cells. Our results indicate that MYCN and
      MYC regulate BMI1 gene expression at the transcriptional level and that
      dysregulation of the BMI1 gene mediated by MYCN or MYC overexpression, confers
      increased cell proliferation during neuroblastoma genesis and tumor progression.

PMID- 21856783
TI  - MiR-365: a mechanosensitive microRNA stimulates chondrocyte differentiation
      through targeting histone deacetylase 4.
AB  - Mechanical stress plays an essential role in tissue development and remodeling.
      In this study, we determined the role of microRNA in chondrocyte
      mechanotransduction. Using microarray, we identified miR-365 as a
      mechanoresponsive microRNA in parallel to mechanical induction of Indian hedgehog
      (Ihh) in primary chicken chondrocytes cultured in 3-dimensional collagen
      scaffoldings under cyclic loading (1 Hz, 5% elongation). Interestingly,
      expression of miR-365 is elevated in the prehypertrophic zone of the growth
      plate, coinciding with the Ihh expression region in vivo. MiR-365 significantly
      stimulates chondrocyte proliferation and differentiation. MiR-365 increases
      expression of Ihh and the hypertrophic marker type X collagen, whereas anti-miR
      365 inhibits the expression of these genes. We identified histone deacetylase 4
      (HDAC4), an inhibitor of chondrocyte hypertrophy, as a target of miR-365. MiR-365
      inhibits both endogenous HDAC4 protein levels as well as the activity of a
      reporter gene bearing the 3'-untranslated region of HDAC4 mRNA. Conversely,
      inhibition of endogenous miR-365 relieves the repression of HDAC4. Mutation of
      the miR-365 binding site in HDAC4 mRNA abolishes miR-365-mediated repression of
      the reporter gene activity. Overexpression of HDAC4 reverses miR-365 stimulation
      of chondrocyte differentiation markers including Ihh, Col X, and Runx2. Moreover,
      inhibition of miR-365 abolishes mechanical stimulation of chondrocyte
      differentiation. Taken together, miR-365 is the first identified mechanically
      responsive microRNA that regulates chondrocyte differentiation via directly
      targeting HDAC4.

PMID- 21856785
TI  - MicroRNA-126 modulates endothelial SDF-1 expression and mobilization of Sca
      1(+)/Lin(-) progenitor cells in ischaemia.
AB  - AIMS: MicroRNA-126 (miR-126), which is enriched in endothelial cells, plays a
      role in angiogenesis. Based on the seed sequence, miR-126 can also be predicted
      to regulate vasculogenesis by modulating the endothelial expression of stromal
      cell-derived factor-1 (SDF-1). METHODS AND RESULTS: Using miR-reporter
      constructs, we first validated that miR-126 inhibits SDF-1 expression in
      endothelial cells in vitro. Next, we investigated the potential relevance of this
      observation with respect to the mobilization of progenitor cells. For this, we
      studied the migration of human CD34+ progenitor cells towards chemotactic factors
      present in endothelial cell-conditioned medium. Antagomir-induced silencing of
      miR-126 elevated SDF-1 expression by human umbilical vein endothelial cells and
      enhanced migration of the CD34+ cells. In a murine model of hind limb ischaemia,
      a striking increase in the number of circulating Sca-1(+)/Lin(-) progenitor cells
      in antagomir-126-treated mice was observed when compared with scramblemir-treated
      controls. Immunohistochemical staining of capillaries in the post-ischaemic
      gastrocnemius muscle of miR-126-silenced mice revealed elevated SDF-1 expressing
      CD31-positive capillaries, whereas a mobilizing effect of miR-126 inhibition was
      not detected in healthy control animals. CONCLUSION: miR-126 can regulate the
      expression of SDF-1 in endothelial cells. In the context of an ischaemic event,
      systemic silencing of miR-126 leads to the mobilization of Sca-1(+)/Lin(-)
      progenitor cells into the peripheral circulation, potentially in response to
      elevated SDF-1 expression by endothelial cells present in the ischaemic tissue.

PMID- 21856784
TI  - Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted
      lipidomic and gene expression study.
AB  - Chronic alcohol consumption is associated with fatty liver disease in mammals.
      The object of this study was to gain an understanding of dysregulated lipid
      metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach.
      Liquid chromatography tandem mass spectrometry was used to analyze several lipid
      classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters,
      sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from
      control and alcohol-fed mice. The interpretation of lipidomic data was augmented
      by gene expression analyses for important metabolic enzymes in the lipid pathways
      studied. Alcohol feeding was associated with i) increased hepatic free fatty acid
      levels and decreased fatty acyl-CoA levels associated with decreased
      mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis,
      respectively; ii) increased hepatic ceramide levels associated with higher levels
      of the precursor molecules sphingosine and sphinganine; and iii) increased
      hepatic levels of the endocannabinoid anandamide associated with decreased
      expression of its catabolic enzyme fatty acid amide hydrolase. The unique
      combination of lipidomic and gene expression analyses allows for a better
      mechanistic understanding of dysregulated lipid metabolism in the development of
      alcoholic fatty liver disease.

PMID- 21856786
TI  - Prokineticin receptor 1 (PKR1) signalling in cardiovascular and kidney functions.
AB  - Prokineticins (PK1 and PK2) are peptide hormones that exert their biological
      activity via two common G-protein-coupled receptors: prokineticin receptor (PKR)
      1 and 2. Their physiology was originally explored mostly in the context of
      angiogenic actions in the reproductive tract and gut motility. Since autocrine
      and paracrine loops have been established between PK2 and PKR1 in the heart, in
      this review we focus on the PK2/PKR1 signalling in the functions of the heart and
      kidney. PKR1 signalling is required for cardiomyocyte survival and angiogenesis.
      In the mouse model of myocardial infarction, intracardiac transient PKR1
      transfection protects the structure and function of the heart. Gain- and loss-of
      function studies reveal that PKR1 in mouse heart up-regulates its own ligand and
      PK2, which in turn acts as a paracrine signal and promotes epicardin-positive
      progenitor cell differentiation into a vasculogenic cell type. Transgenic mice
      over-expressing PKR1 in cardiomyocytes exhibit increased neovascularization. Loss
      of PKR1 causes structural and functional changes in the heart and kidney. In
      isolated epicardin-positive progenitor cells from the kidney, PK2, acting via
      PKR1, stimulates differentiation of these progenitor cells into endothelial and
      smooth muscle cells. Taken together, these data show that PK2/PKR1 is involved in
      postnatal cardiac and renal neovascularization. The knowledge gained from these
      studies should facilitate the discovery of therapeutic interventions in heart and
      kidney diseases targeting PKR1.

PMID- 21856787
TI  - Disruption of fuel servicing in the myocardium: from 'eutaxy and efficiency' to
      'ataxy and inefficiency'.

PMID- 21856788
TI  - Exercise-induced GH secretion in the assessment of GH deficiency in adult
      individuals.
AB  - OBJECTIVE: The role of exercise testing in the assessment of GH deficiency (GHD)
      in adult patients is currently unclear. This study aimed at evaluating the
      diagnostic value of exercise-induced GH levels in the detection of severe GHD in
      adult patients. METHODS: Fourteen patients confirmed to have severe GHD according
      to current guidelines and 20 healthy control individuals (CI) exercised for 120 
      min at 50-60% of their individual VO2(max). GH was measured before and every 30 
      min throughout exercise. The diagnostic value of predicting GHD was assessed by
      performing receiver operating characteristics (ROC) analysis for each time point
      of GH assessment. To optimise comparability within the study population a sub
      analysis with ten individuals specifically matched for gender, age, body mass
      index and waist was performed. RESULTS: Exercise-induced GH secretion was
      significantly lower in patients with GHD than in CI (P<0.001). Area under the ROC
      curve (AUC(ROC)) was 0.954+/-0.033, 0.993+/-0.009, 0.989+/-0.012 and 0.992+/
      0.009 for the overall population and 0.870+/-0.086, 0.980+/-0.024, 0.970+/-0.034
      and 0.978+/-0.027 for the matched individuals at 30, 60, 90 and 120  min of
      exercise respectively. At 60  min of exercise a cut off GH value of 2.4  ng/ml
      translates into a sensitivity of 100% and a specificity of 95 and 90% in the
      diagnosis of GHD for the overall population and matched individuals respectively.
      CONCLUSION: GH assessment during a standardised aerobic exercise of moderate
      intensity is a reliable test with high diagnostic accuracy in predicting severe
      GHD in adult individuals. Based on the current findings exercise duration of 60 
      min appears to be sufficient for diagnostic purposes.

PMID- 21856789
TI  - The accuracy of diagnostic tests for GH deficiency in adults: a systematic review
      and meta-analysis.
AB  - CONTEXT: The diagnostic accuracy of tests used to diagnose GH deficiency (GHD) in
      adults is unclear. OBJECTIVE: We conducted a systematic review and meta-analysis
      of studies that provided data on the available diagnostic tests. DATA SOURCES: We
      searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of
      Sciences, and Scopus) through April 2011. STUDY SELECTION: Review of reference
      lists and contact with experts identified additional candidate studies.
      Reviewers, working independently and in duplicate, determined study eligibility.
      DATA EXTRACTION: reviewers, working independently and in duplicate, determined
      the methodological quality of studies and collected descriptive, quality, and
      outcome data. DATA SYNTHESIS: Twenty-three studies provided diagnostic accuracy
      data; none provided patient outcome data. Studies had fair methodological
      quality, used several reference standards, and included over 1100 patients.
      Several tests based on direct or indirect stimulation of GH release were
      associated with good diagnostic accuracy, although most were assessed in one or
      two studies decreasing the strength of inference due to small sample size. Serum
      levels of GH or IGF1 had low diagnostic accuracy. Pooled sensitivity and
      specificity of the two most commonly used stimulation tests were found to be 95
      and 89% for the insulin tolerance test and 73 and 81% for the GHRH+arginine test
      respectively. Meta-analytic estimates for accuracy were associated with
      substantial heterogeneity. CONCLUSION: Several tests with reasonable diagnostic
      accuracy are available for the diagnosis of GHD in adults. The supporting
      evidence, however, is at high risk of bias (due to heterogeneity, methodological
      limitations, and imprecision).

PMID- 21856790
TI  - Comment on: evidence of lifetime susceptibility to Tropheryma whipplei in
      patients with Whipple's disease.

PMID- 21856791
TI  - Antimicrobial susceptibilities of Francisella tularensis subsp. holarctica
      strains isolated from humans in the Central Anatolia region of Turkey.
AB  - OBJECTIVES: To assess the in vitro susceptibility of Francisella tularensis
      subsp. holarctica biovar II strains to 24 antimicrobial agents. METHODS: Thirty
      nine F. tularensis strains isolated from humans in the Central Anatolia region of
      Turkey were examined. Each isolate was identified by conventional and molecular
      techniques. MICs of aminoglycosides, tetracyclines, fluoroquinolones, macrolides,
      penicillins, cephalosporins, imipenem, clindamycin, linezolid, chloramphenicol
      and rifampicin were determined using the Etest method on glucose/cysteine blood
      agar plates. Interpretation of results was made according to CLSI clinical
      breakpoints. RESULTS: All strains were susceptible to aminoglycosides,
      tetracyclines, chloramphenicol, rifampicin and three fluoroquinolones. In
      contrast, resistance to penicillins, cephalosporins, carbapenems, macrolides and
      clindamycin was observed for all isolates. Fluoroquinolones had the lowest
      MIC(50) and MIC(90). CONCLUSIONS: All strains were susceptible to the antibiotics
      traditionally used to treat tularaemia, such as streptomycin (MIC(90) 1.5 mg/L),
      gentamicin (MIC(90) 0.25 mg/L), tetracycline (MIC(90) 0.38 mg/L) and
      chloramphenicol (MIC(90) 0.25 mg/L). Since fluoroquinolones showed the lowest MIC
      values, and have important advantages over aminoglycosides, including ease of
      oral administration and lower toxicities, quinolones have the potential for being
      effective first-line therapy for tularaemia.

PMID- 21856792
TI  - Vacuolar transport in tobacco leaf epidermis cells involves a single route for
      soluble cargo and multiple routes for membrane cargo.
AB  - We tested if different classes of vacuolar cargo reach the vacuole via distinct
      mechanisms by interference at multiple steps along the transport route. We show
      that nucleotide-free mutants of low molecular weight GTPases, including Rab11,
      the Rab5 members Rha1 and Ara6, and the tonoplast-resident Rab7, caused induced
      secretion of both lytic and storage vacuolar cargo. In situ analysis in leaf
      epidermis cells indicates a sequential action of Rab11, Rab5, and Rab7 GTPases.
      Compared with Rab5 members, mutant Rab11 mediates an early transport defect
      interfering with the arrival of cargo at prevacuoles, while mutant Rab7 inhibits
      the final delivery to the vacuole and increases cargo levels in prevacuoles. In
      contrast with soluble cargo, membrane cargo may follow different routes.
      Tonoplast targeting of an alpha-TIP chimera was impaired by nucleotide-free Rha1,
      Ara6, and Rab7 similar to soluble cargo. By contrast, the tail-anchored tonoplast
      SNARE Vam3 shares only the Rab7-mediated vacuolar deposition step. The most
      marked difference was observed for the calcineurin binding protein CBL6, which
      was insensitive to all Rab mutants tested. Unlike soluble cargo, alpha-TIP and
      Vam3, CBL6 transport to the vacuole was COPII independent. The results indicate
      that soluble vacuolar proteins follow a single route to vacuoles, while membrane
      spanning proteins may use at least three different transport mechanisms.

PMID- 21856793
TI  - Combined noninvasive imaging and modeling approaches reveal metabolic
      compartmentation in the barley endosperm.
AB  - The starchy endosperm of cereals is a priori taken as a metabolically uniform
      tissue. By applying a noninvasive assay based on (13)C/(1)H-magnetic resonance
      imaging (MRI) to barley (Hordeum vulgare) grains, we uncovered metabolic
      compartmentation in the endosperm. (13)C-Suc feeding during grain filling showed
      that the primary site of Ala synthesis was the central region of the endosperm,
      the part of the caryopsis experiencing the highest level of hypoxia. Region
      specific metabolism in the endosperm was characterized by flux balance analysis
      (FBA) and metabolite profiling. FBA predicts that in the central region of the
      endosperm, the tricarboxylic acid cycle shifts to a noncyclic mode, accompanied
      by elevated glycolytic flux and the accumulation of Ala. The metabolic
      compartmentation within the endosperm is advantageous for the grain's carbon and
      energy economy, with a prominent role being played by Ala aminotransferase. An
      investigation of caryopses with a genetically perturbed tissue pattern
      demonstrated that Ala accumulation is a consequence of oxygen status, rather than
      being either tissue specific or dependent on the supply of Suc. Hence the (13)C
      Ala gradient can be used as an in vivo marker for hypoxia. The combination of MRI
      and metabolic modeling offers opportunities for the noninvasive analysis of
      metabolic compartmentation in plants.

PMID- 21856794
TI  - Conservation and purifying selection of transcribed genes located in a rice
      centromere.
AB  - Recombination is strongly suppressed in centromeric regions. In chromosomal
      regions with suppressed recombination, deleterious mutations can easily
      accumulate and cause degeneration of genes and genomes. Surprisingly, the
      centromere of chromosome8 (Cen8) of rice (Oryza sativa) contains several
      transcribed genes. However, it remains unclear as to what selective forces drive
      the evolution and existence of transcribed genes in Cen8. Sequencing of
      orthologous Cen8 regions from two additional Oryza species, Oryza glaberrima and
      Oryza brachyantha, which diverged from O. sativa 1 and 10 million years ago,
      respectively, revealed a set of seven transcribed Cen8 genes conserved across all
      three species. Chromatin immunoprecipitation analysis with the centromere
      specific histone CENH3 confirmed that the sequenced orthologous regions are part
      of the functional centromere. All seven Cen8 genes have undergone purifying
      selection, representing a striking phenomenon of active gene survival within a
      recombination-free zone over a long evolutionary time. The coding sequences of
      the Cen8 genes showed sequence divergence and mutation rates that were
      significantly reduced from those of genes located on the chromosome arms. This
      suggests that Oryza has a mechanism to maintain the fidelity and functionality of
      Cen8 genes, even when embedded in a sea of repetitive sequences and transposable
      elements.

PMID- 21856797
TI  - FDA moves closer to new requirements for NTI drugs.

PMID- 21856798
TI  - Ticagrelor approved for acute coronary syndrome.

PMID- 21856795
TI  - The chloroplast calcium sensor CAS is required for photoacclimation in
      Chlamydomonas reinhardtii.
AB  - The plant-specific calcium binding protein CAS (calcium sensor) has been
      localized in chloroplast thylakoid membranes of vascular plants and green algae.
      To elucidate the function of CAS in Chlamydomonas reinhardtii, we generated and
      analyzed eight independent CAS knockdown C. reinhardtii lines (cas-kd). Upon
      transfer to high-light (HL) growth conditions, cas-kd lines were unable to
      properly induce the expression of LHCSR3 protein that is crucial for
      nonphotochemical quenching. Prolonged exposure to HL revealed a severe light
      sensitivity of cas-kd lines and caused diminished activity and recovery of
      photosystem II (PSII). Remarkably, the induction of LHCSR3, the growth of cas-kd
      lines under HL, and the performance of PSII were fully rescued by increasing the
      calcium concentration in the growth media. Moreover, perturbing cellular Ca(2+)
      homeostasis by application of the calmodulin antagonist W7 or the G-protein
      activator mastoparan impaired the induction of LHCSR3 expression in a
      concentration-dependent manner. Our findings demonstrate that CAS and Ca(2+) are
      critically involved in the regulation of the HL response and particularly in the
      control of LHCSR3 expression.

PMID- 21856799
TI  - Report suggests steps to improve safety of drug supply.

PMID- 21856800
TI  - First Mexico hospital pharmacy conference focuses on patient safety.

PMID- 21856801
TI  - Clopidogrel hyporesponsiveness: are we all the same?

PMID- 21856803
TI  - Inventory management of compounded sterile preparation areas.

PMID- 21856804
TI  - Pycnogenol for chronic venous insufficiency.

PMID- 21856805
TI  - Elevated international normalized ratio values associated with concomitant use of
      warfarin and ceftriaxone.
AB  - PURPOSE: The case of a patient receiving long-term warfarin therapy who
      experienced elevated International Normalized Ratio (INR) values on two occasions
      after injections of ceftriaxone is reported. SUMMARY: An elderly woman (age, 67
      years) with multiple comorbidities who had been receiving warfarin therapy for
      about 8 years was given an intramuscular injection of ceftriaxone 1 g for the
      treatment of a urinary tract infection. Four days later, her INR (which had
      recently ranged from 1.9 to 3.0 at a weekly warfarin dosage of 52.5-54.5 mg) was
      10.74. One scheduled warfarin dose was withheld and 5 mg of phytonadione
      administered; one day later, the INR was 3.4 (goal, 2.5-3.5). INR values remained
      stable for several weeks until the patient again received a 1-g ceftriaxone
      injection for an infection (she was also prescribed oral cefuroxime and
      phenazopyridine); four days later, the INR was 16.99. Again, the scheduled
      warfarin dose was withheld and 5 mg of phytonadione administered. One day later,
      the INR had declined to 4.6 but remained above the target range; therefore,
      warfarin was withheld for a second day, after which the patient received 7.5 mg
      of warfarin sodium daily for two days, resulting in an INR decrease to 2.1. The
      patient continued to receive 7.5 mg of warfarin sodium daily, and at one-week
      follow-up the INR value (2.5) was within the therapeutic range. CONCLUSION: A 67
      year-old American Indian woman with previously stable INR values during long-term
      warfarin therapy after mitral valve replacement surgery had INR elevations on two
      occasions after receiving ceftriaxone for urinary tract infections.

PMID- 21856806
TI  - Pharmacokinetics of aminoglycosides in patients with chronic spinal cord injury.
AB  - PURPOSE: The pharmacokinetics of amino-glycosides in patients with chronic spinal
      cord injury (SCI) is reviewed. SUMMARY: SCI is associated with many physiological
      changes that can affect disposition of drugs such as aminoglycosides; therefore,
      dosing of aminoglycosides in this population can be challenging. In general,
      volume of distribution is significantly higher in the SCI population compared
      with the non-SCI population; however, clearance and half-life may be larger or no
      different. When gentamicin is administered intramuscularly, there is no
      difference in bioavailability when the dose is administered below the level of
      the injury but absorption appears to be slower in patients with SCI compared with
      the non-SCI population. Several methods of laboratory assessment of renal
      function, such as serum creatinine (SCr), 24-hour urine creatinine clearance
      (CL(cr)), and cystatin C, have advantages and limitations associated with their
      use in the SCI population. The majority of evidence suggests that SCr and various
      estimation equations are not accurate methods for assessing renal function in
      this population. Although measured CL(cr) by 24-hour urine collection is not
      dependent on muscle mass, wide intrapatient variability in CL(cr) results is
      still observed. Cystatin C may be a good option in this population; however, its
      use is limited by its availability. CONCLUSION: Determining appropriate
      aminoglycoside dosage in patients with SCI is challenging because such patients
      exhibit physiological changes that lead to their having different aminoglycoside
      pharmacokinetic values than the general population. Monitoring of aminoglycoside
      concentrations and calculation of patient-specific pharmacokinetic values can
      help guide dosage in this patient population.

PMID- 21856807
TI  - Pharmacodynamic evaluation of i.v. antimicrobials against Pseudomonas aeruginosa
      samples collected from U.S. hospitals.
AB  - PURPOSE: Selected i.v. antimicrobials were evaluated against Pseudomonas
      aeruginosa isolates collected from U.S. hospitals to predict the likelihood of
      achieving maximal bactericidal activity. METHODS: The pharmacodynamic profiles of
      ceftazidime, doripenem, imipenem-cilastatin, levofloxacin, meropenem, and
      piperacillin-tazobactam were simulated for 5000 adult patients using
      pharmacokinetic data from infected patients with the minimum inhibitory
      concentrations of 6142 P. aeruginosa isolates in U.S. hospitals collected during
      2009. The probability of achieving bactericidal activity in this population,
      referred to as the cumulative fraction of response (CFR), was calculated for each
      antimicrobial. An optimal regimen was defined as achieving a CFR of >=90%.
      RESULTS: The majority of isolates were collected from male inpatients who were
      not in an intensive care unit (ICU) and were over age 65 years. Standard dosing
      for all antimicrobials failed to achieve optimal CFRs, regardless of hospital
      location. While high-dose prolonged infusions improved the CFRs for the beta
      lactams, optimal exposures were only attained by doripenem (2 g every 8 hours
      infused over 1 hour; 0.5-2 g every 8 hours infused over 4 hours) and meropenem (2
      g every 8 hours infused over 0.5 and 3 hours) for all isolates. Non-ICU isolates
      had approximately 5-10% higher CFRs compared with those collected in the ICU.
      Lower-respiratory-tract isolates had a lower predicted CFR than did isolates from
      the blood and skin or wounds. CONCLUSION: Simulated pharmacodynamic profiles of
      i.v. antimicrobials commonly used to treat P. aeruginosa indicated that higher
      dosages and prolonged infusion times are needed to achieve optimal exposure for
      bactericidal activity.

PMID- 21856808
TI  - Boxed warning inconsistencies between drug information resources and the
      prescribing information.
AB  - PURPOSE: Inconsistencies in boxed warnings between drug information resources and
      the manufacturer's prescribing information (PI) were evaluated. METHODS: This
      study was a cross-sectional evaluation of boxed warnings in Black-BoxRx, DrugDex,
      Facts and Comparisons, Epocrates, Lexicomp, and PDR.net conducted in June 2010.
      New molecular entities with boxed warnings and PI that conformed to current Food
      and Drug Administration labeling requirements were included. Each resource was
      reviewed for warnings that appeared verbatim with the full boxed warning in the
      PI. Two drug information pharmacists independently reviewed the remaining
      nonverbatim boxed warnings to determine concordance with the boxed warning
      summary in the "highlights" section of the PI. Tests of proportions were used to
      examine differences among resources in the proportion of warnings concordant with
      the PI. Interrater reliability was assessed with the kappa statistic. RESULTS: A
      total of 71 drugs with unique boxed warnings were included in the evaluation.
      Resources revealed varying degrees of discordances with the boxed warning in the
      PI. The resource with the lowest number of verbatim warnings contained a
      significantly higher percentage of warnings with discordant information when
      compared with all other resources (p < 0.0001 for all paired comparisons).
      Interrater reliability was excellent (kappa = 0.86). CONCLUSION: Boxed warning
      information presented in major drug information resources may be missing key
      elements of the official boxed warning in the current PI. The current PI may be
      the most reliable approach to accessing the complete, up-to-date boxed warning
      for a given drug.

PMID- 21856809
TI  - Effect of ascorbic acid on inflammatory markers after cardiothoracic surgery.
AB  - PURPOSE: The effect of ascorbic acid on inflammatory markers after cardiothoracic
      surgery (CTS) was studied. METHODS: In this randomized, double-blind, placebo
      controlled trial, patients undergoing cardiopulmonary bypass graft surgery or
      valve replacement surgery from April 2009 through March 2010 at Hartford Hospital
      were randomized to receive ascorbic acid (2-g loading dose followed by 500 mg
      every 12 hours) or matching placebo the evening before surgery and for four days
      postoperatively. Inflammatory mediators were measured preoperatively and on
      postoperative days 1-4. Intergroup comparisons were performed using two-tailed t
      tests and Fisher's exact test. Multiple comparisons were conducted using repeated
      analyses of variance with Bonferroni tests. RESULTS: Of the 62 patients screened,
      24 met the study inclusion criteria. Of these, 13 were assigned to receive
      ascorbic acid and 11 received placebo. Ascorbic acid did not affect the natural
      course of inflammatory marker rise for C-reactive protein (CRP) concentration,
      white blood cell (WBC) count, or fibrinogen concentration versus placebo at any
      evaluated time point (p > 0.05 for all intergroup comparisons). Intragroup
      analyses demonstrated significant differences among baseline and postoperative
      measures of all inflammatory mediators (p < 0.05). No significant differences
      were noted in inflammatory markers between patients undergoing cardiothoracic
      surgery with or without cardiopulmonary bypass, regardless of treatment group.
      CONCLUSION: Ascorbic acid did not attenuate the rise in inflammatory markers
      after CTS when compared with placebo. The use of off-pump surgery did not
      significantly change the levels of CRP and fibrinogen or the WBC count
      postoperatively when compared with on-pump surgery with a biocompatible polymer
      coating.

PMID- 21856810
TI  - Factors associated with the publication of scholarly articles by pharmacists.
AB  - PURPOSE: Factors associated with the publication of scholarly articles by
      pharmacists were evaluated. METHODS: A Web-based survey was distributed to all
      pharmacists who published at least one scholarly article in selected pharmacy and
      medical journals in 2008. All scholarly works published in the American Journal
      of Health-System Pharmacy, Annals of Pharmacotherapy, and Pharmacotherapy during
      the study period were categorized by study design using a predetermined
      algorithm. A secondary group of pharmacists who published in at least 1 of 10
      selected medical journals during the study period was also evaluated to identify
      any differences between those who published in pharmacy versus medical journals.
      RESULTS: The final number of usable responses was 254, for an adjusted response
      rate of 72.9%. Factors identified as the most helpful for facilitating
      publication efforts included time allotment, mentorship, and collaborative
      efforts. "Lack of time" was reported as the most important barrier to
      publication. The majority of respondents (73%, n = 182) published their first
      article during a training program (academic program, residency, or fellowship).
      Of the 468 scholarly works published in the selected pharmacy journals during the
      study period, review articles were most common (38.7%, n = 177). CONCLUSION: The
      most influential factors on the publication efforts by pharmacists were time
      allotment, collaboration between pharmacy colleagues and within multidisciplinary
      teams, and training in research methods and scientific writing. Introduction to
      the publication process during training programs appeared to influence future
      propensity toward scholarly participation. Review and descriptive articles were
      the most frequently published types of articles in the pharmacy literature.

PMID- 21856811
TI  - Stability of cyclosporine solutions stored in polypropylene-polyolefin bags and
      polypropylene syringes.
AB  - PURPOSE: The stability of cyclosporine diluted to 0.2 or 2.5 mg/mL with 0.9%
      sodium chloride injection or 5% dextrose injection and stored in polypropylene
      polyolefin containers or polypropylene syringes was evaluated. METHODS:
      Intravenous cyclosporine solutions (0.2 and 2.5 mg/mL) were aseptically prepared
      and transferred to 250-mL polypropylene-polyolefin bags or 60-mL polypropylene
      syringes. Chemical stability was measured using a stability-indicating high
      performance liquid chromatography (HPLC) assay. Physical stability was assessed
      by visual inspection and a dynamic light scattering (DLS) method. RESULTS: After
      14 days, HPLC assay showed that the samples of i.v. cyclosporine stored in
      polypropylene-polyolefin bags remained chemically stable (>98% of initial amount
      remaining); the physical stability of the samples was confirmed by DLS and visual
      inspection. The samples stored in polypropylene syringes were found to contain an
      impurity (attributed to leaching of a syringe component by the solution) that
      could be detected by HPLC after 1 day; on further investigation, no leaching was
      detected when the syringes were exposed to undiluted i.v. cyclosporine 50 mg/mL
      for 10 minutes. CONCLUSION: Samples of i.v. cyclosporine solutions of 0.2 and 2.5
      mg/mL diluted in 0.9% sodium chloride injection or 5% dextrose injection and
      stored at 25  degrees C in polypropylene-polyolefin bags were physically and
      chemically stable for at least 14 days. When stored in polypropylene syringes,
      the samples were contaminated by an impurity within 1 day; however, the short
      term (i.e., <=10 minutes) use of the syringes for the preparation and transfer of
      i.v. cyclosporine solution is considered safe.

PMID- 21856812
TI  - Physiology, reductionism, and translational medicine: the right mix.

PMID- 21856813
TI  - Sulfatide-activated type II NKT cells prevent allergic airway inflammation by
      inhibiting type I NKT cell function in a mouse model of asthma.
AB  - Asthma is a common chronic inflammatory disease involving many different cell
      types. Recently, type I natural killer T (NKT) cells have been demonstrated to
      play a crucial role in the development of asthma. However, the roles of type II
      NKT cells in asthma have not been investigated before. Interestingly, type I and
      type II NKT cells have been shown to have opposing roles in antitumor immunity,
      antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated
      type II NKT cells could prevent allergic airway inflammation by inhibiting type I
      NKT cell function in asthma. Strikingly, in our mouse model, activation of type
      II NKT cells by sulfatide administration and adoptive transfer of sulfatide
      activated type II NKT cells result in reduced-inflammation cell infiltration in
      the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in
      the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1.
      Furthermore, it is found that the activation of sulfatide-reactive type II NKT
      cells leads to the functional inactivation of type I NKT cells, including the
      proliferation and cytokine secretion. Our data reveal that type II NKT cells
      activated by glycolipids, such as sulfatide, may serve as a novel approach to
      treat allergic diseases and other disorders characterized by inappropriate type I
      NKT cell activation.

PMID- 21856814
TI  - Delayed stress fiber formation mediates pulmonary myofibroblast differentiation
      in response to TGF-beta.
AB  - Myofibroblast differentiation induced by transforming growth factor-beta (TGF
      beta) and characterized by de novo expression of smooth muscle (SM)-specific
      proteins is a key process in wound healing and in the pathogenesis of fibrosis.
      We have previously shown that TGF-beta-induced expression and activation of serum
      response factor (SRF) is required for this process. In this study, we examined
      the signaling mechanism for SRF activation by TGF-beta as it relates to pulmonary
      myofibroblast differentiation. TGF-beta stimulated a profound, but delayed (18-24
      h), activation of Rho kinase and formation of actin stress fibers, which
      paralleled SM alpha-actin expression. The translational inhibitor cycloheximide
      blocked these processes without affecting Smad-dependent gene transcription.
      Inhibition of Rho kinase by Y-27632 or depolymerization of actin by latrunculin B
      resulted in inhibition TGF-beta-induced SRF activation and SM alpha-actin
      expression, having no effect on Smad signaling. Conversely, stabilization of
      actin stress fibers by jasplakinolide was sufficient to drive these processes in
      the absence of TGF-beta. TGF-beta promoted a delayed nuclear accumulation of the
      SRF coactivator megakaryoblastic leukemia-1 (MKL1)/myocardin-related
      transcription factor-A, which was inhibited by latrunculin B. Furthermore, TGF
      beta also induced MKL1 expression, which was inhibited by latrunculin B, by SRF
      inhibitor CCG-1423, or by SRF knockdown. Together, these data suggest a triphasic
      model for myofibroblast differentiation in response to TGF-beta that involves 1)
      initial Smad-dependent expression of intermediate signaling molecules driving Rho
      activation and stress fiber formation, 2) nuclear accumulation of MKL1 and
      activation of SRF as a result of actin polymerization, and 3) SRF-dependent
      expression of MKL1, driving further myofibroblast differentiation.

PMID- 21856815
TI  - Positive end-expiratory pressure and surfactant decrease lung injury during
      initiation of ventilation in fetal sheep.
AB  - The initiation of ventilation in preterm, surfactant-deficient sheep without
      positive end-expiratory pressure (PEEP) causes airway injury and lung
      inflammation. We hypothesized that PEEP and surfactant treatment would decrease
      the lung injury from initiation of ventilation with high tidal volumes. Fetal
      sheep at 128-day gestational age were randomized to ventilation with: 1) no PEEP,
      no surfactant; 2) 8-cmH(2)O PEEP, no surfactant; 3) no PEEP + surfactant; 4) 8
      cmH(2)O PEEP + surfactant; or 5) control (2-cmH(2)O continuous positive airway
      pressure) (n = 6-7/group). After maternal anesthesia and hysterotomy, the head
      and chest were exteriorized, and the fetus was intubated. While maintaining
      placental circulation, the fetus was ventilated for 15 min with a tidal volume
      escalating to 15 ml/kg using heated, humidified, 100% nitrogen. The fetus then
      was returned to the uterus, and tissue was collected after 30 min for evaluation
      of early markers of lung injury. Lambs receiving both surfactant and PEEP had
      increased dynamic compliance, increased static lung volumes, and decreased total
      protein and heat shock proteins 70 and 60 in bronchoalveolar lavage fluid
      compared with other groups. Ventilation, independent of PEEP or surfactant,
      increased mRNA expression of acute phase response genes and proinflammatory
      cytokine mRNA in the lung tissue compared with controls. PEEP decreased mRNA for
      cytokines (2-fold) compared with groups receiving no PEEP. Surfactant
      administration further decreased some cytokine mRNAs and changed the distribution
      of early growth response protein-1 expression. The use of PEEP during initiation
      of ventilation at birth decreased early mediators of lung injury. Surfactant
      administration changed the distribution of injury and had a moderate additive
      protective effect.

PMID- 21856816
TI  - Rho-kinase inhibition alleviates pulmonary hypertension in transgenic mice
      expressing a dominant-negative type II bone morphogenetic protein receptor gene.
AB  - Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized
      by a sustained elevation in the pulmonary artery pressure and subsequent right
      heart failure. The activation of Rho/Rho-kinase activity and the beneficial
      effect of Rho-kinase inhibition have been demonstrated in several experimental
      models of pulmonary hypertension. However, it remains unclear whether Rho-kinase
      inhibitors can also be used against pulmonary hypertension associated with
      mutations in the type II bone morphogenetic protein receptor (BMPRII) gene.
      Transgenic mice expressing a dominant-negative BMPRII gene (with an arginine to
      termination mutation at amino acid 899) in smooth muscle by a tetracycline-gene
      switch system (SM22-tet-BMPR2(R899X) mice) were examined. They developed an
      elevated right ventricular systolic pressure (RVSP), right ventricular (RV)
      hypertrophy, muscularization of small pulmonary arteries, and an associated
      disturbed blood flow in their lungs. The Rho/Rho-kinase activity and Smad
      activity were determined by a Western blot analysis by detecting GTP-RhoA and the
      phosphorylation of myosin phosphatase target subunit 1, Smad1, and Smad2. In the
      lungs of SM22-tet-BMPR2(R899X) mice, the Rho/Rho-kinase activity was elevated
      significantly, whereas the Smad activity was almost unchanged. Fasudil, a Rho
      kinase inhibitor, significantly decreased RVSP, alleviated RV hypertrophy and
      muscularization of small pulmonary arteries, and improved blood flow in SM22-tet
      BMPR2(R899X) mice, although it did not alter Smad signaling. Our study
      demonstrates that Rho/Rho-kinase signaling is activated via a Smad-independent
      pathway in an animal model of pulmonary hypertension with a BMPRII mutation in
      the cytoplasmic tail domain. Rho-kinase inhibition is therefore a possible
      therapeutic approach for the treatment of PAH associated with genetic mutation.

PMID- 21856817
TI  - Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative
      stress and causes pulmonary vasodilation in neonatal pulmonary hypertension.
AB  - Although inhaled NO (iNO) therapy is often effective in treating infants with
      persistent pulmonary hypertension of the newborn (PPHN), up to 40% of patients
      fail to respond, which may be partly due to abnormal expression and function of
      soluble guanylate cyclase (sGC). To determine whether altered sGC expression or
      activity due to oxidized sGC contributes to high pulmonary vascular resistance
      (PVR) and poor NO responsiveness, we studied the effects of cinaciguat (BAY 58
      2667), an sGC activator, on pulmonary artery smooth muscle cells (PASMC) from
      normal fetal sheep and sheep exposed to chronic intrauterine pulmonary
      hypertension (i.e., PPHN). We found increased sGC alpha(1)- and beta(1)-subunit
      protein expression but lower basal cGMP levels in PPHN PASMC compared with normal
      PASMC. To determine the effects of cinaciguat and NO after sGC oxidation in
      vitro, we measured cGMP production by normal and PPHN PASMC treated with
      cinaciguat and the NO donor, sodium nitroprusside (SNP), before and after
      exposure to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an sGC oxidizer),
      hyperoxia (fraction of inspired oxygen 0.50), or hydrogen peroxide (H(2)O(2)).
      After treatment with ODQ, SNP-induced cGMP generation was markedly reduced but
      the effects of cinaciguat were increased by 14- and 64-fold in PPHN fetal PASMC,
      respectively (P < 0.01 vs. controls). Hyperoxia or H(2)O(2) enhanced cGMP
      production by cinaciguat but not SNP in PASMC. To determine the hemodynamic
      effects of cinaciguat in vivo, we compared serial responses to cinaciguat and ACh
      in fetal lambs after ductus arteriosus ligation. In contrast with the impaired
      vasodilator response to ACh, cinaciguat-induced pulmonary vasodilation was
      significantly increased. After birth, cinaciguat caused a significantly greater
      fall in PVR than either 100% oxygen, iNO, or ACh. We conclude that cinaciguat
      causes more potent pulmonary vasodilation than iNO in experimental PPHN. We
      speculate that increased NO-insensitive sGC may contribute to the pathogenesis of
      PPHN, and cinaciguat may provide a novel treatment of severe pulmonary
      hypertension.

PMID- 21856818
TI  - Angiotensin II activates AMPK for execution of apoptosis through energy-dependent
      and -independent mechanisms.
AB  - At the cellular level, 5'-AMP-activated protein kinase (AMPK) serves as a
      critical link between energy homeostasis and the regulation of fundamental
      biological activities, including apoptosis. Angiotensin (Ang) II plays a key role
      in fibrotic lung remodeling. We recently demonstrated that Ang II induces
      apoptosis in pulmonary artery endothelial cells (PAEC) through the Ang type 2
      receptor (AT(2)). AT(2) activates Src-homology two-domain-containing phosphatase
      2 (SHP-2) in a signaling cascade leading to Bcl-x(L) mRNA destabilization and
      initiation of intrinsic apoptosis. We investigated the requirement of AMPK and
      ATP generation for Ang II-induced apoptosis in PAEC. Ang II activated AMPK, which
      was required for ATP generation. Inhibition of ATP production by compound C, an
      AMPK inhibitor, or by oligomycin suppressed Ang II-induced apoptosis. Experiments
      in Chinese hamster ovary-K1 cells expressing ectopic AT(2) (wild-type, mutant
      D90A, or carboxy terminal truncated mutant tC319) demonstrated that AT(2)
      activation of AMPK required the active conformation of the receptor and the
      carboxy terminal 44 amino acids. AMPK associated with and activated SHP-2 and was
      required for Bcl-x(L) mRNA destabilization. These are the first findings
      demonstrating that AMPK is activated by Ang II to produce ATP required for
      apoptosis. Our data also indicate that AMPK plays an energy-independent role by
      mediating SHP-2 activation.

PMID- 21856820
TI  - Pathways involved in reductant distribution during photobiological H(2)
      production by Rhodobacter sphaeroides.
AB  - We used global transcript analyses and mutant studies to investigate the pathways
      that impact H(2) production in the photosynthetic bacterium Rhodobacter
      sphaeroides. We found that H(2) production capacity is related to the levels of
      expression of the nitrogenase and hydrogenase enzymes and the enzymes of the
      Calvin-Benson-Bassham pathway.

PMID- 21856821
TI  - Comparative genomic analysis of Acinetobacter oleivorans DR1 to determine strain
      specific genomic regions and gentisate biodegradation.
AB  - The comparative genomics of Acinetobacter oleivorans DR1 assayed with A. baylyi
      ADP1, A. calcoaceticus PHEA-2, and A. baumannii ATCC 17978 revealed that the
      incorporation of phage-related genomic regions and the absence of transposable
      elements have contributed to the large size (4.15 Mb) of the DR1 genome. A
      horizontally transferred genomic region and a higher proportion of
      transcriptional regulator- and signal peptide-coding genes were identified as
      characteristics of the DR1 genome. Incomplete glucose metabolism, metabolic
      pathways of aromatic compounds, biofilm formation, antibiotics and metal
      resistance, and natural competence genes were conserved in four compared genomes.
      Interestingly, only strain DR1 possesses gentisate 1,2-dioxygenase (nagI) and
      grows on gentisate, whereas other species cannot. Expression of the nagI gene was
      upregulated during gentisate utilization, and four downstream open reading frames
      (ORFs) were cotranscribed, supporting the notion that gentisate metabolism is a
      unique characteristic of strain DR1. The genomic analysis of strain DR1 provides
      additional insights into the function, ecology, and evolution of Acinetobacter
      species.

PMID- 21856819
TI  - Prostaglandin E2 protects murine lungs from bleomycin-induced pulmonary fibrosis
      and lung dysfunction.
AB  - Prostaglandin E(2) (PGE(2)) is a lipid mediator that is produced via the
      metabolism of arachidonic acid by cyclooxygenase enzymes. In the lung, PGE(2)
      acts as an anti-inflammatory factor and plays an important role in tissue repair
      processes. Although several studies have examined the role of PGE(2) in the
      pathogenesis of pulmonary fibrosis in rodents, results have generally been
      conflicting, and few studies have examined the therapeutic effects of PGE(2) on
      the accompanying lung dysfunction. In this study, an established model of
      pulmonary fibrosis was used in which 10-12-wk-old male C57BL/6 mice were
      administered a single dose (1.0 mg/kg) of bleomycin via oropharyngeal aspiration.
      To test the role of prostaglandins in this model, mice were dosed, via surgically
      implanted minipumps, with either vehicle, PGE(2) (1.32 MUg/h), or the
      prostacyclin analog iloprost (0.33 MUg/h) beginning 7 days before or 14 days
      after bleomycin administration. Endpoints assessed at 7 days after bleomycin
      administration included proinflammatory cytokine levels and measurement of
      cellular infiltration into the lung. Endpoints assessed at 21 days after
      bleomycin administration included lung function assessment via invasive
      (FlexiVent) analysis, cellular infiltration, lung collagen content, and
      semiquantitative histological analysis of the degree of lung fibrosis (Ashcroft
      method). Seven days after bleomycin administration, lymphocyte numbers and
      chemokine C-C motif ligand 2 expression were significantly lower in PGE(2)- and
      iloprost-treated animals compared with vehicle-treated controls (P < 0.05). When
      administered 7 days before bleomycin challenge, PGE(2) also protected against the
      decline in lung static compliance, lung fibrosis, and collagen production that is
      associated with 3 wk of bleomycin exposure. However, PGE(2) had no therapeutic
      effect on these parameters when administered 14 days after bleomycin challenge.
      In summary, PGE(2) prevented the decline in lung static compliance and protected
      against lung fibrosis when it was administered before bleomycin challenge but had
      no therapeutic effect when administered after bleomycin challenge.

PMID- 21856822
TI  - beta-lactams and florfenicol antibiotics remain bioactive in soils while
      ciprofloxacin, neomycin, and tetracycline are neutralized.
AB  - It is generally assumed that antibiotic residues in soils select for antibiotic
      resistant bacteria. This assumption was tested by separately adding 10 different
      antibiotics (>=200 ppm) to three soil-water slurries (silt-loam, sand-loam, and
      sand; 20% soil [wt/vol]) and incubating mixtures for 24 h at room temperature.
      The antibiotic activity of the resultant supernatant was assessed by culturing a
      sensitive Escherichia coli strain in the filter-sterilized supernatant augmented
      with Luria-Bertani broth. We found striking differences in the abilities of
      supernatants to suppress growth of the indicator E. coli. Ampicillin,
      cephalothin, cefoxitin, ceftiofur, and florfenicol supernatants completely
      inhibited growth while bacterial growth was uninhibited in the presence of
      neomycin, tetracycline, and ciprofloxacin supernatants. High-performance liquid
      chromatography (HPLC) analysis demonstrated that cefoxitin and florfenicol were
      almost completely retained in the supernatants, whereas tetracycline and
      ciprofloxacin were mostly removed. Antibiotic dissipation in soil, presumably
      dominated by adsorption mechanisms, was sufficient to neutralize 200 ppm of
      tetracycline; this concentration is considerably higher than reported
      contamination levels. Soil pellets from the tetracycline slurries were
      resuspended in a minimal volume of medium to maximize the interaction between
      bacteria and soil particles, but sensitive bacteria were still unaffected by
      tetracycline (P = 0.6). Thus, residual antibiotics in soil do not necessarily
      exert a selective pressure, and the degree to which the pharmaceutical remains
      bioactive depends on the antibiotic. Efforts to control antibiotic contamination
      would be better directed toward compounds that retain biological activity in
      soils (e.g., cephalosporins and florfenicol) because these are the antibiotics
      that could exert a selective pressure in the environment.

PMID- 21856823
TI  - Identification of a perchlorate reduction genomic island with novel regulatory
      and metabolic genes.
AB  - A comparative analysis of the genomes of four dissimilatory (per)chlorate
      reducing bacteria has revealed a genomic island associated with perchlorate
      reduction. In addition to the characterized metabolic genes for perchlorate
      reductase and chlorite dismutase, the island contains multiple conserved
      uncharacterized genes possibly involved in electron transport and regulation.

PMID- 21856824
TI  - Comparing the chlorine disinfection of detached biofilm clusters with those of
      sessile biofilms and planktonic cells in single- and dual-species cultures.
AB  - Although the detachment of cells from biofilms is of fundamental importance to
      the dissemination of organisms in both public health and clinical settings, the
      disinfection efficacies of commonly used biocides on detached biofilm particles
      have not been investigated. Therefore, the question arises whether cells in
      detached aggregates can be killed with disinfectant concentrations sufficient to
      inactivate planktonic cells. Burkholderia cepacia and Pseudomonas aeruginosa were
      grown in standardized laboratory reactors as single species and in coculture.
      Cluster size distributions in chemostats and biofilm reactor effluent were
      measured. Chlorine susceptibility was assessed for planktonic cultures, attached
      biofilm, and particles and cells detached from the biofilm. Disinfection
      tolerance generally increased with a higher percentage of larger cell clusters in
      the chemostat and detached biofilm. Samples with a lower percentage of large
      clusters were more easily disinfected. Thus, disinfection tolerance depended on
      the cluster size distribution rather than sample type for chemostat and detached
      biofilm. Intact biofilms were more tolerant to chlorine independent of species.
      Homogenization of samples led to significantly increased susceptibility in all
      biofilm samples as well as detached clusters for single-species B. cepacia, B.
      cepacia in coculture, and P. aeruginosa in coculture. The disinfection efficacy
      was also dependent on species composition; coculture was advantageous to the
      survival of both species when grown as a biofilm or as clusters detached from
      biofilm but, surprisingly, resulted in a lower disinfection tolerance when they
      were grown as a mixed planktonic culture.

PMID- 21856825
TI  - Differential regulation of orthologous chitinase genes in mycoparasitic
      Trichoderma species.
AB  - Mycoparasitic Trichoderma species have expanded numbers of fungal subgroup C
      chitinases that contain multiple carbohydrate binding modules and could thus be
      important for fungal cell wall degradation during the mycoparasitic attack. In
      this study, we analyzed the gene regulation of subgroup C chitinases in the
      mycoparasite Trichoderma virens. In addition to regulation by nutritional
      stimuli, we found complex expression patterns in different parts of the fungal
      colony, and also, the mode of cultivation strongly influenced subgroup C
      chitinase transcript levels. Thus, the regulation of these genes is governed by a
      combination of colony-internal and -external signals. Our results showed
      completely different expression profiles of subgroup C chitinase genes in T.
      virens than in a previous study with T. atroviride, although both fungi are
      potent mycoparasites. Only a few subgroup C chitinase orthologues were found in
      T. atroviride and T. virens, and even those showed substantially divergent gene
      expression patterns. Microscopic analysis revealed morphogenetic differences
      between T. atroviride and T. virens, which could be connected to differential
      subgroup C chitinase gene expression. The biological function of fungal subgroup
      C chitinases therefore might not be as clear-cut as previously anticipated. They
      could have pleiotropic roles and might be involved in both degradation of
      exogenous chitinous carbon sources, including other fungal cell walls, and
      recycling of their own cell walls during hyphal development and colony formation.

PMID- 21856826
TI  - Methodologies for Salmonella enterica subsp. enterica subtyping: gold standards
      and alternatives.
AB  - For more than 80 years, subtyping of Salmonella enterica has been routinely
      performed by serotyping, a method in which surface antigens are identified based
      on agglutination reactions with specific antibodies. The serotyping scheme, which
      is continuously updated as new serovars are discovered, has generated over time a
      data set of the utmost significance, allowing long-term epidemiological
      surveillance of Salmonella in the food chain and in public health control.
      Conceptually, serotyping provides no information regarding the phyletic
      relationships inside the different Salmonella enterica subspecies. In
      epidemiological investigations, identification and tracking of salmonellosis
      outbreaks require the use of methods that can fingerprint the causative strains
      at a taxonomic level far more specific than the one achieved by serotyping.
      During the last 2 decades, alternative methods that could successfully identify
      the serovar of a given strain by probing its DNA have emerged, and molecular
      biology-based methods have been made available to address phylogeny and
      fingerprinting issues. At the same time, accredited diagnostics have become
      increasingly generalized, imposing stringent methodological requirements in terms
      of traceability and measurability. In these new contexts, the hand-crafted
      character of classical serotyping is being challenged, although it is widely
      accepted that classification into serovars should be maintained. This review
      summarizes and discusses modern typing methods, with a particular focus on those
      having potential as alternatives for classical serotyping or for subtyping
      Salmonella strains at a deeper level.

PMID- 21856827
TI  - Pyrroloquinoline quinone biosynthesis gene pqqC, a novel molecular marker for
      studying the phylogeny and diversity of phosphate-solubilizing pseudomonads.
AB  - Many root-colonizing pseudomonads are able to promote plant growth by increasing
      phosphate availability in soil through solubilization of poorly soluble rock
      phosphates. The major mechanism of phosphate solubilization by pseudomonads is
      the secretion of gluconic acid, which requires the enzyme glucose dehydrogenase
      and its cofactor pyrroloquinoline quinone (PQQ). The main aim of this study was
      to evaluate whether a PQQ biosynthetic gene is suitable to study the phylogeny of
      phosphate-solubilizing pseudomonads. To this end, two new primers, which
      specifically amplify the pqqC gene of the Pseudomonas genus, were designed. pqqC
      fragments were amplified and sequenced from a Pseudomonas strain collection and
      from a natural wheat rhizosphere population using cultivation-dependent and
      cultivation-independent approaches. Phylogenetic trees based on pqqC sequences
      were compared to trees obtained with the two concatenated housekeeping genes rpoD
      and gyrB. For both pqqC and rpoD-gyrB, similar main phylogenetic clusters were
      found. However, in the pqqC but not in the rpoD-gyrB tree, the group of
      fluorescent pseudomonads producing the antifungal compounds 2,4
      diacetylphloroglucinol and pyoluteorin was located outside the Pseudomonas
      fluorescens group. pqqC sequences from isolated pseudomonads were differently
      distributed among the identified phylogenetic groups than pqqC sequences derived
      from the cultivation-independent approach. Comparing pqqC phylogeny and phosphate
      solubilization activity, we identified one phylogenetic group with high
      solubilization activity. In summary, we demonstrate that the gene pqqC is a novel
      molecular marker that can be used complementary to housekeeping genes for
      studying the diversity and evolution of plant-beneficial pseudomonads.

PMID- 21856828
TI  - Role of Mrx fimbriae of Xenorhabdus nematophila in competitive colonization of
      the nematode host.
AB  - Xenorhabdus nematophila engages in mutualistic associations with the infective
      juvenile (IJ) stage of specific entomopathogenic nematodes. Mannose-resistant
      (Mrx) chaperone-usher-type fimbriae are produced when the bacteria are grown on
      nutrient broth agar (NB agar). The role of Mrx fimbriae in the colonization of
      the nematode host has remained unresolved. We show that X. nematophila grown on
      LB agar produced flagella rather than fimbriae. IJs propagated on X. nematophila
      grown on LB agar were colonized to the same extent as those propagated on NB
      agar. Further, progeny IJs were normally colonized by mrx mutant strains that
      lacked fimbriae both when bacteria were grown on NB agar and when coinjected into
      the insect host with aposymbiotic nematodes. The mrx strains were not
      competitively defective for colonization when grown in the presence of wild-type
      cells on NB agar. In addition, a phenotypic variant strain that lacked fimbriae
      colonized as well as the wild-type strain. In contrast, the mrx strains displayed
      a competitive colonization defect in vivo. IJ progeny obtained from insects
      injected with comixtures of nematodes carrying either the wild-type or the mrx
      strain were colonized almost exclusively with the wild-type strain. Likewise,
      when insects were coinjected with aposymbiotic IJs together with a comixture of
      the wild-type and mrx strains, the resulting IJ progeny were predominantly
      colonized with the wild-type strain. These results revealed that Mrx fimbriae
      confer a competitive advantage during colonization in vivo and provide new
      insights into the role of chaperone-usher fimbriae in the life cycle of X.
      nematophila.

PMID- 21856829
TI  - Four-year evaluation of the effect of vaccination against Coxiella burnetii on
      reduction of animal infection and environmental contamination in a naturally
      infected dairy sheep flock.
AB  - Vaccination is considered one of the best options for controlling Coxiella
      burnetii infection in livestock. The efficacy of a phase I vaccine was
      investigated over 4 years in a sheep flock with confirmed C. burnetii infection.
      Shedding was not detected in ewes and yearlings in the last 2 years, but C.
      burnetii still persisted in the environment.

PMID- 21856830
TI  - Microbial inactivation for safe and rapid diagnostics of infectious samples.
AB  - The high risk associated with biological threat agents dictates that any
      suspicious sample be handled under strict surety and safety controls and
      processed under high-level containment in specialized laboratories. This study
      attempted to find a rapid, reliable, and simple method for the complete
      inactivation of a wide range of pathogens, including spores, vegetative bacteria,
      and viruses, while preserving microbial nucleic acid fragments suitable for PCRs
      and proteinaceous epitopes for detection by immunoassays. Formaldehyde, hydrogen
      peroxide, and guanidium thiocyanate did not completely inactivate high titers of
      bacterial spores or viruses after 30 min at 21 degrees C. Glutaraldehyde and
      sodium hypochlorite showed high microbicidal activity but obliterated the PCR or
      enzyme-linked immunosorbent assay (ELISA) detection of bacterial spores or
      viruses. High-level inactivation (more than 6 log(10)) of bacterial spores
      (Bacillus atrophaeus), vegetative bacteria (Pseudomonas aeruginosa), an RNA virus
      (the alphavirus Pixuna virus), or a DNA virus (the orthopoxvirus vaccinia virus)
      was attained within 30 min at 21 degrees C by treatment with either peracetic
      acid or cupric ascorbate with minimal hindrance of subsequent PCR tests and
      immunoassays. The data described here should provide the basis for quickly
      rendering field samples noninfectious for further analysis under lower-level
      containment and considerably lower cost.

PMID- 21856831
TI  - Ability of Bifidobacterium breve to grow on different types of milk: exploring
      the metabolism of milk through genome analysis.
AB  - We have investigated the occurrence of bifidobacteria in human milk samples, and
      we provide evidence regarding the predominance of members of the Bifidobacterium
      breve species in this environment. Moreover, evaluation of the growth
      capabilities and transcriptomic analyses of one representative isolate of this
      species, i.e., B. breve 4L, on different milk types were performed.

PMID- 21856833
TI  - Effect of glucose on the fatty acid composition of Cupriavidus necator JMP134
      during 2,4-dichlorophenoxyacetic acid degradation: implications for lipid-based
      stable isotope probing methods.
AB  - Combining lipid biomarker profiling with stable isotope probing (SIP) is a
      powerful technique for studying specific microbial populations responsible for
      the degradation of organic pollutants in various natural environments. However,
      the presence of other easily degradable substrates may induce significant
      physiological changes by altering both the rate of incorporation of the target
      compound into the biomass and the microbial lipid profiles. In order to test this
      hypothesis, Cupriavidus necator JMP134, a 2,4-dichlorophenoxyacetic acid (2,4-D)
      degrading bacterium, was incubated with [(13)C]2,4-D, [(13)C]glucose, or mixtures
      of both substrates alternatively labeled with (13)C. C. necator JMP134 exhibited
      a preferential use of 2,4-D over glucose. The isotopic analysis showed that
      glucose had only a small effect on the incorporation of the acetic chain of 2,4-D
      into the biomass (at days 2 and 3) and no effect on that of the benzenic ring.
      The addition of glucose did change the fatty acid methyl ester (FAME)
      composition. However, the overall FAME isotopic signature reflected that of the
      entire biomass. Compound-specific individual isotopic analyses of FAME
      composition showed that the (13)C-enriched FAME profiles were slightly or not
      affected when tracing the 2,4-D acetic chain or 2,4-D benzenic ring,
      respectively. This batch study is a necessary step for validating the use of
      lipid-based SIP methods in complex environments.

PMID- 21856834
TI  - Mechanisms of fluoroquinolone resistance in Escherichia coli isolates from food
      producing animals.
AB  - Eleven multidrug-resistant Escherichia coli isolates (comprising 6 porcine and 5
      bovine field isolates) displaying fluoroquinolone (FQ) resistance were selected
      from a collection obtained from the University Veterinary Hospital (Dublin,
      Ireland). MICs of nalidixic acid and ciprofloxacin were determined by Etest. All
      showed MICs of nalidixic acid of >256 MUg/ml and MICs of ciprofloxacin ranging
      from 4 to >32 MUg/ml. DNA sequencing was used to identify mutations within the
      quinolone resistance-determining regions of target genes, and quantitative real
      time PCR (qRT-PCR) was used to evaluate the expression of the major porin, OmpF,
      and component genes of the AcrAB-TolC efflux pump and its associated regulatory
      loci. Decreased MIC values to nalidixic acid and/or ciprofloxacin were observed
      in the presence of the efflux pump inhibitor phenylalanine-arginine-beta
      naphthylamide (PAbetaN) in some but not all isolates. Several mutations were
      identified in genes coding for quinolone target enzymes (3 to 5 mutations per
      strain). All isolates harbored GyrA amino acid substitutions at positions 83 and
      87. Novel GyrA (Asp87 -> Ala), ParC (Ser80 -> Trp), and ParE (Glu460 -> Val)
      substitutions were observed. The efflux activity of these isolates was evaluated
      using a semiautomated ethidium bromide (EB) uptake assay. Compared to wild-type
      E. coli K-12 AG100, isolates accumulated less EB, and in the presence of PAbetaN
      the accumulation of EB increased. Upregulation of the acrB gene, encoding the
      pump component of the AcrAB-TolC efflux pump, was observed in 5 of 11 isolates,
      while 10 isolates showed decreased expression of OmpF. This study identified
      multiple mechanisms that likely contribute to resistance to quinolone-based drugs
      in the field isolates studied.

PMID- 21856832
TI  - Sponge-associated bacteria are strictly maintained in two closely related but
      geographically distant sponge hosts.
AB  - The giant barrel sponges Xestospongia muta and Xestospongia testudinaria are
      ubiquitous in tropical reefs of the Atlantic and Pacific Oceans, respectively.
      They are key species in their respective environments and are hosts to diverse
      assemblages of bacteria. These two closely related sponges from different oceans
      provide a unique opportunity to examine the evolution of sponge-associated
      bacterial communities. Mitochondrial cytochrome oxidase subunit I gene sequences
      from X. muta and X. testudinaria showed little divergence between the two
      species. A detailed analysis of the bacterial communities associated with these
      sponges, comprising over 900 full-length 16S rRNA gene sequences, revealed
      remarkable similarity in the bacterial communities of the two species. Both
      sponge-associated communities include sequences found only in the two
      Xestospongia species, as well as sequences found also in other sponge species and
      are dominated by three bacterial groups, Chloroflexi, Acidobacteria, and
      Actinobacteria. While these groups consistently dominate the bacterial
      communities revealed by 16S rRNA gene-based analysis of sponge-associated
      bacteria, the depth of sequencing undertaken in this study revealed clades of
      bacteria specifically associated with each of the two Xestospongia species, and
      also with the genus Xestospongia, that have not been found associated with other
      sponge species or other ecosystems. This study, comparing the bacterial
      communities associated with closely related but geographically distant sponge
      hosts, gives new insight into the intimate relationships between marine sponges
      and some of their bacterial symbionts.

PMID- 21856835
TI  - Characterization of multidrug-resistant Escherichia coli isolates from animals
      presenting at a university veterinary hospital.
AB  - In this study, we examined molecular mechanisms associated with multidrug
      resistance (MDR) in a collection of Escherichia coli isolates recovered from
      hospitalized animals in Ireland. PCR and DNA sequencing were used to identify
      genes associated with resistance. Class 1 integrons were prevalent (94.6%) and
      contained gene cassettes recognized previously and implicated mainly in
      resistance to aminoglycosides, beta-lactams, and trimethoprim (aadA1, dfrA1
      aadA1, dfrA17-aadA5, dfrA12-orfF-aadA2, bla(OXA-30)-aadA1, aacC1-orf1-orf2-aadA1,
      dfr7). Class 2 integrons (13.5%) contained the dfrA1-sat1-aadA1 gene array. The
      most frequently occurring phenotypes included resistance to ampicillin (97.3%),
      chloramphenicol (75.4%), florfenicol (40.5%), gentamicin (54%), neomycin (43.2%),
      streptomycin (97.3%), sulfonamide (98.6%), and tetracycline (100%). The
      associated resistance determinants detected included bla(TEM), cat, floR, aadB,
      aphA1, strA-strB, sul2, and tet(B), respectively. The bla(CTX-M-2) gene, encoding
      an extended-spectrum beta-lactamase (ESbetaL), and bla(CMY-2), encoding an AmpC
      like enzyme, were identified in 8 and 18 isolates, respectively. The mobility of
      the resistance genes was demonstrated using conjugation assays with a
      representative selection of isolates. High-molecular-weight plasmids were found
      to be responsible for resistance to multiple antimicrobial compounds. The study
      demonstrated that animal-associated commensal E. coli isolates possess a diverse
      repertoire of transferable genetic determinants. Emergence of ESbetaLs and AmpC
      like enzymes is particularly significant. To our knowledge, the bla(CTX-M-2) gene
      has not previously been reported in Ireland.

PMID- 21856836
TI  - Effect of sodium bisulfite injection on the microbial community composition in a
      brackish-water-transporting pipeline.
AB  - Pipelines transporting brackish subsurface water, used in the production of
      bitumen by steam-assisted gravity drainage, are subject to frequent corrosion
      failures despite the addition of the oxygen scavenger sodium bisulfite (SBS).
      Pyrosequencing of 16S rRNA genes was used to determine the microbial community
      composition for planktonic samples of transported water and for sessile samples
      of pipe-associated solids (PAS) scraped from pipeline cutouts representing
      corrosion failures. These were obtained from upstream (PAS-616P) and downstream
      (PAS-821TP and PAS-821LP, collected under rapid-flow and stagnant conditions,
      respectively) of the SBS injection point. Most transported water samples had a
      large fraction (1.8% to 97% of pyrosequencing reads) of Pseudomonas not found in
      sessile pipe samples. The sessile population of PAS-616P had methanogens
      (Methanobacteriaceae) as the main (56%) community component, whereas
      Deltaproteobacteria of the genera Desulfomicrobium and Desulfocapsa were not
      detected. In contrast, PAS-821TP and PAS-821LP had lower fractions (41% and 0.6%)
      of Methanobacteriaceae archaea but increased fractions of sulfate-reducing
      Desulfomicrobium (18% and 48%) and of bisulfite-disproportionating Desulfocapsa
      (35% and 22%) bacteria. Hence, SBS injection strongly changed the sessile
      microbial community populations. X-ray diffraction analysis of pipeline scale
      indicated that iron carbonate was present both upstream and downstream, whereas
      iron sulfide and sulfur were found only downstream of the SBS injection point,
      suggesting a contribution of the bisulfite-disproportionating and sulfate
      reducing bacteria in the scale to iron corrosion. Incubation of iron coupons with
      pipeline waters indicated iron corrosion coupled to the formation of methane.
      Hence, both methanogenic and sulfidogenic microbial communities contributed to
      corrosion of pipelines transporting these brackish waters.

PMID- 21856837
TI  - Aedes aegypti membrane-bound alkaline phosphatase expressed in Escherichia coli
      retains high-affinity binding for Bacillus thuringiensis Cry4Ba toxin.
AB  - Glycosylphosphatidylinositol-linked alkaline phosphatase (GPI-ALP) from the
      epithelial membrane of the larval midgut of Aedes aegypti was previously
      identified as a functional receptor of the Bacillus thuringiensis Cry4Ba toxin.
      Here, heterologous expression in Escherichia coli of the cloned ALP, lacking the
      secretion signal and GPI attachment sequences, and assessment of its binding
      characteristics were further investigated. The 54-kDa His tag-fused ALP
      overexpressed as an inclusion body was soluble when phosphate buffer (pH 7.5) was
      supplemented with 8 M urea. After renaturation in a nickel-nitrilotriacetic acid
      (Ni-NTA) affinity column, the refolded ALP protein was able to retain its
      phosphatase activity. This refolded ALP also showed binding to the 65-kDa
      activated Cry4Ba toxin under nondenaturing (dot blot) conditions. Quantitative
      binding analysis using a quartz crystal microbalance revealed that the purified
      ALP immobilized on a gold electrode was bound by the Cry4Ba toxin in a
      stoichiometry of approximately 1:2 and with high affinity (dissociation constant
      [K(d)] of ~14 nM) which is comparable to that calculated from kinetic parameters
      (dissociation rate constant [k(off)]/binding constant [k(on)]). Altogether, the
      data presented here of the E. coli-expressed ALP from A. aegypti retaining high
      affinity toxin binding support our notion that glycosylation of this receptor is
      not required for binding to its counterpart toxin, Cry4Ba.

PMID- 21856838
TI  - Application of the modular approach to an in-house validation study of real-time
      PCR methods for the detection and serogroup determination of verocytotoxigenic
      Escherichia coli.
AB  - European Commission regulation 2073/2005 on the microbiological criteria for food
      requires that Escherichia coli is monitored as an indicator of hygienic
      conditions. Since verocytotoxigenic E. coli (VTEC) strains often cause food-borne
      infections by the consumption of raw food, the Biological Hazards (BIOHAZ) panel
      of the European Food Safety Authority (EFSA) recommended their monitoring in food
      as well. In particular, VTEC strains belonging to serogroups such as O26, O103,
      O111, O145, and O157 are known causative agents of several human outbreaks. Eight
      real-time PCR methods for the detection of E. coli toxin genes and their variants
      (stx(1), stx(2)), the intimin gene (eae), and five serogroup-specific genes have
      been proposed by the European Reference Laboratory for VTEC (EURL-VTEC) as a
      technical specification to the European Normalization Committee (CEN TC275/WG6).
      Here we applied a "modular approach" to the in-house validation of these PCR
      methods. The modular approach subdivides an analytical process into separate
      parts called "modules," which are independently validated based on method
      performance criteria for a limited set of critical parameters. For the VTEC real
      time PCR module, the following parameters are being assessed: specificity,
      dynamic range, PCR efficiency, and limit of detection (LOD). This study describes
      the modular approach for the validation of PCR methods to be used in food
      microbiology, using single-target plasmids as positive controls and showing their
      applicability with food matrices.

PMID- 21856839
TI  - CsgA production by Escherichia coli O157:H7 alters attachment to abiotic surfaces
      in some growth environments.
AB  - The role of curli expression in attachment of Escherichia coli O157:H7 to glass,
      Teflon, and stainless steel (SS) was investigated through the creation of csgA
      knockout mutants in two isolates of E. coli O157:H7. Attachment assays using
      epifluorescence microscopy and measurements of the force of adhesion of bacterial
      cells to the substrates using atomic force microscopy (AFM) force mapping were
      used to determine differences in attachment between wild-type (wt) and csgA
      negative (DeltacsgA) strains following growth in four different media. The
      hydrophobicity of the cells was determined using contact angle measurements (CAM)
      and bacterial adhesion to hydrocarbons (BATH). The attachment assay results
      indicated that DeltacsgA strains attached to glass, Teflon, and SS surfaces in
      significantly different numbers than their wt counterparts in a growth medium
      dependent fashion (P < 0.05). However, no clear correlation was seen between
      attachment numbers, surface type, or growth medium. No correlation was seen
      between BATH and CAM results (R(2) < 0.70). Hydrophobicity differed between the
      wt and DeltacsgA in some cases in a growth medium- and method-dependent fashion
      (P < 0.05). AFM force mapping revealed no significant difference in the forces of
      adhesion to glass and SS surfaces between wt and DeltacsgA strains (P > 0.05) but
      a significantly greater force of adhesion to Teflon for one of the two wt strains
      than for its DeltacsgA counterpart (P < 0.05). This study shows that CsgA
      production by E. coli O157:H7 may alter attachment behavior in some environments;
      however, further investigation is required in order to determine the exact
      relationship between CsgA production and attachment to abiotic surfaces.

PMID- 21856840
TI  - Molecular characterization of multidrug-resistant Escherichia coli isolates from
      Irish cattle farms.
AB  - This study describes the genotypic characteristics of a collection of 100
      multidrug-resistant (MDR) Escherichia coli strains recovered from cattle and the
      farm environment in Ireland in 2007. The most prevalent antimicrobial resistance
      identified was to streptomycin (100%), followed by tetracycline (99%),
      sulfonamides (98%), ampicillin (82%), and neomycin (62%). Resistance was mediated
      predominantly by strA-strB (92%), tetA (67%), sul2 (90%), bla(TEM) (79%), and
      aphA1 (63%) gene markers, respectively. Twenty-seven isolates harbored a class 1
      integrase (intI1), while qacEDelta1 and sul1 markers were identified in 25 and 26
      isolates, respectively. The variable regions of these integrons contained
      aminoglycoside, trimethoprim, and beta-lactam resistance determinants (aadA12,
      aadB-aadA1, bla(OXA-30)-aadA1, dfrA1-aadA1, dfrA7). Class 2 integrons were
      identified less frequently (4%) and contained the gene cassette array dfrA1-sat1
      aadA1. Resistance to ampicillin, neomycin, streptomycin, sulfonamide, and
      tetracycline was associated with transferable high-molecular-weight plasmids, as
      demonstrated by conjugation assays. A panel of virulence markers was screened for
      by PCR, and genes identified included vt1, K5 in 2 isolates, papC in 10 isolates,
      and PAI IV(536) in 37 isolates. MDR commensal E. coli isolates from Irish cattle
      displayed considerable diversity with respect to the genes identified. Our
      findings highlight the importance of the commensal microflora of food-producing
      animals as a reservoir of transferable MDR.

PMID- 21856842
TI  - Myxococcus xanthus swarms are driven by growth and regulated by a pacemaker.
AB  - The principal social activity of Myxococcus xanthus is to organize a dynamic
      multicellular structure, known as a swarm. Although its cell density is high, the
      swarm can grow and expand rapidly. Within the swarm, the individual rod-shaped
      cells are constantly moving, transiently interacting with one another, and
      independently reversing their gliding direction. Periodic reversal is, in fact,
      essential for creating a swarm, and the reversal frequency controls the rate of
      swarm expansion. Chemotaxis toward nutrient has been thought to drive swarming,
      but here the nature of swarm growth and the impact of genetic deletions of
      members of the Frz family of proteins suggest otherwise. We find that three
      cytoplasmic Frz proteins, FrzCD, FrzF, and FrzE, constitute a cyclic pathway that
      sets the reversal frequency. Within each cell these three proteins appear to be
      connected in a negative-feedback loop that produces oscillations whose
      frequencies are finely tuned by methylation and by phosphorylation. This
      oscillator, in turn, drives MglAB, a small G-protein switch, to oscillate between
      its GTP- and GDP-bound states that ultimately determine when the cell moves
      forward or backward. The periodic reversal of interacting rod-shaped cells
      promotes their alignment. Swarm organization ensures that each cell can move
      without blocking the movement of others.

PMID- 21856841
TI  - Norovirus infectivity in humans and persistence in water.
AB  - To examine the long-term infectivity of human norovirus in water, 13 study
      subjects were challenged at different time points with groundwater spiked with
      the prototype human norovirus, Norwalk virus. Norwalk virus spiked in groundwater
      remained infectious after storage at room temperature in the dark for 61 days
      (the last time point tested). The Norwalk virus-seeded groundwater was stored for
      1,266 days and analyzed, after RNase treatment, by reverse transcription
      quantitative PCR (RT-qPCR) to detect Norwalk virus RNA contained within intact
      capsids. Norwalk virus RNA within intact capsids was detected in groundwater for
      1,266 days, with no significant log(10) reduction throughout 427 days and a
      significant 1.10-log(10) reduction by day 1266. Purified Norwalk virus RNA
      (extracted from Norwalk virus virions) persisted for 14 days in groundwater, tap
      water, and reagent-grade water. This study demonstrates that Norwalk virus in
      groundwater can remain detectable for over 3 years and can remain infectious for
      at least 61 days. (ClinicalTrials.gov identifier NCT00313404.).

PMID- 21856843
TI  - Brucella melitensis cyclic di-GMP phosphodiesterase BpdA controls expression of
      flagellar genes.
AB  - Brucella melitensis encounters a variety of conditions and stimuli during its
      life cycle--including environmental growth, intracellular infection, and
      extracellular dissemination--which necessitates flexibility of bacterial
      signaling to promote virulence. Cyclic-di-GMP is a bacterial secondary signaling
      molecule that plays an important role in adaptation to changing environments and
      altering virulence in a number of bacteria. To investigate the role of cyclic-di
      GMP in B. melitensis, all 11 predicted cyclic-di-GMP-metabolizing proteins were
      separately deleted and the effect on virulence was determined. Three of these
      cyclic-di-GMP-metabolizing proteins were found to alter virulence. Deletion of
      the bpdA and bpdB genes resulted in attenuation of virulence of the bacterium,
      while deletion of the cgsB gene produced a hypervirulent strain. In a Vibrio
      reporter system to monitor apparent alteration in levels of cyclic-di-GMP, both
      BpdA and BpdB displayed a phenotype consistent with cyclic-di-GMP-specific
      phosphodiesterases, while CgsB displayed a cyclic-di-GMP synthase phenotype.
      Further analysis found that deletion of bpdA resulted in a dramatic decrease in
      flagellar promoter activities, and a flagellar mutant showed similar phenotypes
      to the bpdA and bpdB mutant strains in mouse models of infection. These data
      indicate a potential role for regulation of flagella in Brucella melitensis via
      cyclic-di-GMP.

PMID- 21856844
TI  - Specificity and role of the Borrelia burgdorferi CtpA protease in outer membrane
      protein processing.
AB  - To further characterize the function of the Borrelia burgdorferi C-terminal
      protease CtpA, we used site-directed mutagenesis to alter the putative CtpA
      cleavage site of one of its known substrates, the outer membrane (OM) porin P13.
      These mutations resulted in only partial blockage of P13 processing. Ectopic
      expression of a C-terminally truncated P13 in B. burgdorferi indicated that the C
      terminal peptide functions as a safeguard against misfolding or mislocalization
      prior to its proteolytic removal by CtpA. In a parallel study of Borrelia
      burgdorferi lipoprotein sorting mechanisms, we observed a lower-molecular-weight
      variant of surface lipoprotein OspC that was particularly prominent with OspC
      mutants that mislocalized to the periplasm or contained C-terminal epitope tags.
      Further investigation revealed that the variant resulted from C-terminal
      proteolysis by CtpA. Together, these findings indicate that CtpA rather
      promiscuously targets polypeptides that lack structurally constrained C termini,
      as proteolysis appears to occur independently of a specific peptide recognition
      sequence. Low-level processing of surface lipoproteins such as OspC suggests the
      presence of a CtpA-dependent quality control mechanism that may sense proper
      translocation of integral outer membrane proteins and surface lipoproteins by
      detecting the release of C-terminal peptides.

PMID- 21856845
TI  - Inhibitory effects of D-amino acids on Staphylococcus aureus biofilm development.
AB  - Biofilms are communities of cells held together by a self-produced extracellular
      matrix typically consisting of protein, exopolysaccharide, and often DNA. A
      natural signal for biofilm disassembly in Bacillus subtilis is certain D-amino
      acids, which are incorporated into the peptidoglycan and trigger the release of
      the protein component of the matrix. D-amino acids also prevent biofilm formation
      by the related Gram-positive bacterium Staphylococcus aureus. Here we employed
      fluorescence microscopy and confocal laser scanning microscopy to investigate how
      D-amino acids prevent biofilm formation by S. aureus. We report that biofilm
      formation takes place in two stages, initial attachment to surfaces, resulting in
      small foci, and the subsequent growth of the foci into large aggregates. D-amino
      acids did not prevent the initial surface attachment of cells but blocked the
      subsequent growth of the foci into larger assemblies of cells. Using protein- and
      polysaccharide-specific stains, we have shown that D-amino acids inhibited the
      accumulation of the protein component of the matrix but had little effect on
      exopolysaccharide production and localization within the biofilm. We conclude
      that D-amino acids act in an analogous manner to prevent biofilm development in
      B. subtilis and S. aureus. Finally, to investigate the potential utility of D
      amino acids in preventing device-related infections, we have shown that surfaces
      impregnated with D-amino acids were effective in preventing biofilm growth.

PMID- 21856846
TI  - The Yersinia enterocolitica phage shock proteins B and C can form homodimers and
      heterodimers in vivo with the possibility of close association between multiple
      domains.
AB  - The Yersinia enterocolitica phage shock protein (Psp) stress response is
      essential for virulence and for survival during the mislocalization of outer
      membrane secretin proteins. The cytoplasmic membrane proteins PspB and PspC are
      critical components involved in regulating psp gene expression and in
      facilitating tolerance to secretin-induced stress. Interactions between PspB and
      PspC monomers might be important for their functions and for PspC stability.
      However, little is known about these interactions and there are conflicting
      reports about the ability of PspC to dimerize. To address this, we have used a
      combination of independent approaches to systematically analyze the ability of
      PspB and PspC to form dimers in vivo. Formaldehyde cross-linking of the
      endogenous chromosomally encoded proteins in Y. enterocolitica revealed discrete
      complexes corresponding in size to PspB-PspB, PspC-PspC, and PspB-PspC. Bacterial
      two-hybrid analysis corroborated these protein associations, but an important
      limitation of the two-hybrid approach was uncovered for PspB. A series of PspB
      and PspC proteins with unique cysteine substitutions at various positions was
      constructed. In vivo disulfide cross-linking experiments with these proteins
      further supported close association between PspB and PspC monomers. Detailed
      cysteine substitution analysis of predicted leucine zipper-like amphipathic
      helices in both PspB and PspC suggested that their hydrophobic faces could form
      homodimerization interfaces.

PMID- 21856847
TI  - Identification of the regulator gene responsible for the acetone-responsive
      expression of the binuclear iron monooxygenase gene cluster in mycobacteria.
AB  - The mimABCD gene cluster encodes the binuclear iron monooxygenase that oxidizes
      propane and phenol in Mycobacterium smegmatis strain MC2 155 and Mycobacterium
      goodii strain 12523. Interestingly, expression of the mimABCD gene cluster is
      induced by acetone. In this study, we investigated the regulator gene responsible
      for this acetone-responsive expression. In the genome sequence of M. smegmatis
      strain MC2 155, the mimABCD gene cluster is preceded by a gene designated mimR,
      which is divergently transcribed. Sequence analysis revealed that MimR exhibits
      amino acid similarity with the NtrC family of transcriptional activators,
      including AcxR and AcoR, which are involved in acetone and acetoin metabolism,
      respectively. Unexpectedly, many homologs of the mimR gene were also found in the
      sequenced genomes of actinomycetes. A plasmid carrying a transcriptional fusion
      of the intergenic region between the mimR and mimA genes with a promoterless
      green fluorescent protein (GFP) gene was constructed and introduced into M.
      smegmatis strain MC2 155. Using a GFP reporter system, we confirmed by deletion
      and complementation analyses that the mimR gene product is the positive regulator
      of the mimABCD gene cluster expression that is responsive to acetone. M. goodii
      strain 12523 also utilized the same regulatory system as M. smegmatis strain MC2
      155. Although transcriptional activators of the NtrC family generally control
      transcription using the sigma(54) factor, a gene encoding the sigma(54) factor
      was absent from the genome sequence of M. smegmatis strain MC2 155. These results
      suggest the presence of a novel regulatory system in actinomycetes, including
      mycobacteria.

PMID- 21856848
TI  - TolC affects virulence gene expression in Vibrio cholerae.
AB  - A Vibrio cholerae tolC mutant showed increased toxT expression in M9 medium, but
      not in the presence of four amino acids that induce cholera toxin production, and
      in LB with high osmolarity but not high pH or temperature. TolC did not affect
      expression of other regulatory genes in the ToxR regulon.

PMID- 21856849
TI  - Vestibules are part of the substrate path in the multidrug efflux transporter
      AcrB of Escherichia coli.
AB  - The path of substrates in the multidrug efflux pump AcrB of Escherichia coli was
      examined by using labeling with a lipophilic substrate mimic, Bodipy FL
      maleimide. Four (out of eight) residues in the vestibule bound the dye,
      suggesting its role in substrate transport, whereas only one (out of nine)
      residue in the central cavity tested positive.

PMID- 21856850
TI  - The Bacillus subtilis GntR family repressor YtrA responds to cell wall
      antibiotics.
AB  - The transglycosylation step of cell wall synthesis is a prime antibiotic target
      because it is essential and specific to bacteria. Two antibiotics, ramoplanin and
      moenomycin, target this step by binding to the substrate lipid II and the
      transglycosylase enzyme, respectively. Here, we compare the ramoplanin and
      moenomycin stimulons in the Gram-positive model organism Bacillus subtilis.
      Ramoplanin strongly induces the LiaRS two-component regulatory system, while
      moenomycin almost exclusively induces genes that are part of the regulon of the
      extracytoplasmic function (ECF) sigma factor sigma(M). Ramoplanin additionally
      induces the ytrABCDEF and ywoBCD operons, which are not part of a previously
      characterized antibiotic-responsive regulon. Cluster analysis reveals that these
      two operons are selectively induced by a subset of cell wall antibiotics that
      inhibit lipid II function or recycling. Repression of both operons requires YtrA,
      which recognizes an inverted repeat in front of its own operon and in front of
      ywoB. These results suggest that YtrA is an additional regulator of cell envelope
      stress responses.

PMID- 21856851
TI  - Nonclassical protein secretion by Bacillus subtilis in the stationary phase is
      not due to cell lysis.
AB  - The carboxylesterase Est55 has been cloned and expressed in Bacillus subtilis
      strains. Est55, which lacks a classical, cleavable N-terminal signal sequence,
      was found to be secreted during the stationary phase of growth such that there is
      more Est55 in the medium than inside the cells. Several cytoplasmic proteins were
      also secreted in large amounts during late stationary phase, indicating that
      secretion in B. subtilis is not unique to Est55. These proteins, which all have
      defined cytoplasmic functions, include GroEL, DnaK, enolase, pyruvate
      dehydrogenase subunits PdhB and PdhD, and SodA. The release of Est55 and those
      proteins into the growth medium is not due to gross cell lysis, a conclusion that
      is supported by several lines of evidence: constant cell density and secretion in
      the presence of chloramphenicol, constant viability count, the absence of EF-Tu
      and SecA in the culture medium, and the lack of effect of autolysin-deficient
      mutants. The shedding of these proteins by membrane vesicles into the medium is
      minimal. More importantly, we have identified a hydrophobic alpha-helical domain
      within enolase that contributes to its secretion. Thus, upon the genetic deletion
      or replacement of a potential membrane-embedding domain, the secretion of plasmid
      gene-encoded mutant enolase is totally blocked, while the wild-type chromosomal
      enolase is secreted normally in the same cultures during the stationary phase,
      indicating differential specificity. We conclude that the secretion of Est55 and
      several cytoplasmic proteins without signal peptides in B. subtilis is a general
      phenomenon and is not a consequence of cell lysis or membrane shedding; instead,
      their secretion is through a process(es) in which protein domain structure plays
      a contributing factor.

PMID- 21856852
TI  - Hydrogen-stimulated carbon acquisition and conservation in Salmonella enterica
      serovar Typhimurium.
AB  - Salmonella enterica serovar Typhimurium can utilize molecular hydrogen for growth
      and amino acid transport during anaerobic growth. Via microarray we identified
      H(2) gas-affected gene expression changes in Salmonella. The addition of H(2)
      caused altered expression of 597 genes, of which 176 genes were upregulated and
      421 were downregulated. The significantly H(2)-upregulated genes include those
      that encode proteins involved in the transport of iron, manganese, amino acids,
      nucleosides, and sugars. Genes encoding isocitrate lyase (aceA) and malate
      synthase (aceB), both involved in the carbon conserving glyoxylate pathway, and
      genes encoding the enzymes of the d-glucarate and d-glycerate pathways (gudT,
      gudD, garR, garL, garK) are significantly upregulated by H(2). Cells grown with
      H(2) showed markedly increased AceA enzyme activity compared to cells without
      H(2). Mutant strains with deletion of either aceA or aceB had reduced H(2)
      dependent growth rates. Genes encoding the glutamine-specific transporters (glnH,
      glnP, glnQ) were upregulated by H(2), and cells grown with H(2) showed increased
      [(14)C]glutamine uptake. Similarly, the mannose uptake system genes (manX, manY)
      were upregulated by H(2,) and cells grown with H(2) showed about 2.0-fold
      increased [(14)C]d-mannose uptake compared to the cells grown without H(2).
      Hydrogen stimulates the expression of genes involved in nutrient and carbon
      acquisition and carbon-conserving pathways, linking carbon and energy metabolism
      to sustain H(2)-dependent growth.

PMID- 21856853
TI  - A novel factor controlling bistability in Bacillus subtilis: the YmdB protein
      affects flagellin expression and biofilm formation.
AB  - Cells of Bacillus subtilis can either be motile or sessile, depending on the
      expression of mutually exclusive sets of genes that are required for flagellum or
      biofilm formation, respectively. Both activities are coordinated by the master
      regulator SinR. We have analyzed the role of the previously uncharacterized ymdB
      gene for bistable gene expression in B. subtilis. We observed a strong
      overexpression of the hag gene encoding flagellin and of other genes of the
      sigma(D)-dependent motility regulon in the ymdB mutant, whereas the two major
      operons for biofilm formation, tapA-sipW-tasA and epsA-O, were not expressed. As
      a result, the ymdB mutant is unable to form biofilms. An analysis of the
      individual cells of a population revealed that the ymdB mutant no longer
      exhibited bistable behavior; instead, all cells are short and motile. The
      inability of the ymdB mutant to form biofilms is suppressed by the deletion of
      the sinR gene encoding the master regulator of biofilm formation, indicating that
      SinR-dependent repression of biofilm genes cannot be relieved in a ymdB mutant.
      Our studies demonstrate that lack of expression of SlrR, an antagonist of SinR,
      is responsible for the observed phenotypes. Overexpression of SlrR suppresses the
      effects of a ymdB mutation.

PMID- 21856854
TI  - Neisserial Correia repeat-enclosed elements do not influence the transcription of
      pil genes in Neisseria gonorrhoeae and Neisseria meningitidis.
AB  - Two human-specific neisserial pathogens, Neisseria gonorrhoeae and Neisseria
      meningitidis, require the expression of type IV pili (tfp) for initial attachment
      to the host during infection. However, the mechanisms controlling the assembly
      and functionality of tfp are poorly understood. It is known that the gonococcal
      pilE gene, encoding the major subunit, is positively regulated by IHF, a
      multifunctional DNA binding protein. A neisserial specific repetitive DNA
      sequence, termed the Correia repeat-enclosed element (CREE) is situated upstream
      of three pil loci: pilHIJKX (pilH-X), pilGD, and pilF. CREEs have been shown to
      contain strong promoters, and some CREE variants contain a functional IHF binding
      site. CREEs might therefore be involved in the regulation of tfp biogenesis in
      pathogenic Neisseria. Site-directed and deletion mutagenesis on promoter::cat
      reporter constructs demonstrated that transcription of pilH-X and pilGD is from a
      sigma(70) promoter and is independent of the CREE. The insertion of a CREE in the
      pilF promoter region in N. meningitidis generated a functional sigma(70)
      promoter. However, there is also a functional promoter at this position in N.
      gonorrhoeae, where there is no CREE. These results suggest CREE insertion in
      these three pil loci does not influence transcription and that IHF does not
      coordinately regulate tfp biogenesis.

PMID- 21856855
TI  - The Bacillus subtilis extracytoplasmic function sigma factor sigma(V) is induced
      by lysozyme and provides resistance to lysozyme.
AB  - Bacteria encounter numerous environmental stresses which can delay or inhibit
      their growth. Many bacteria utilize alternative sigma factors to regulate subsets
      of genes required to overcome different extracellular assaults. The largest group
      of these alternative sigma factors are the extracytoplasmic function (ECF) sigma
      factors. In this paper, we demonstrate that the expression of the ECF sigma
      factor sigma(V) in Bacillus subtilis is induced specifically by lysozyme but not
      other cell wall-damaging agents. A mutation in sigV results in increased
      sensitivity to lysozyme killing, suggesting that sigma(V) is required for
      lysozyme resistance. Using reverse transcription (RT)-PCR, we show that the
      previously uncharacterized gene yrhL (here referred to as oatA for O
      acetyltransferase) is in a four-gene operon which includes sigV and rsiV. In
      quantitative RT-PCR experiments, the expression of oatA is induced by lysozyme
      stress. Lysozyme induction of oatA is dependent upon sigma(V). Overexpression of
      oatA in a sigV mutant restores lysozyme resistance to wild-type levels. This
      suggests that OatA is required for sigma(V)-dependent resistance to lysozyme. We
      also tested the ability of lysozyme to induce the other ECF sigma factors and
      found that only the expression of sigV is lysozyme inducible. However, we found
      that the other ECF sigma factors contributed to lysozyme resistance. We found
      that sigX and sigM mutations alone had very little effect on lysozyme resistance
      but when combined with a sigV mutation resulted in significantly greater lysozyme
      sensitivity than the sigV mutation alone. This suggests that sigV, sigX, and sigM
      may act synergistically to control lysozyme resistance. In addition, we show that
      two ECF sigma factor-regulated genes, dltA and pbpX, are required for lysozyme
      resistance. Thus, we have identified three independent mechanisms which B.
      subtilis utilizes to avoid killing by lysozyme.

PMID- 21856856
TI  - Dissecting complex metabolic integration provides direct genetic evidence for
      CodY activation by guanine nucleotides.
AB  - The global regulator CodY controls the expression of dozens of metabolic genes
      and genes mediating adaptation to nutrient availability in many low-G+C Gram
      positive bacteria. Branched-chain amino acids L-isoleucine, L-leucine, and L
      valine (ILV) activate CodY both in vivo and in vitro, and genes that direct their
      synthesis (ilv, ybgE, and ywaA) are highly repressed by CodY, creating a
      potential negative feedback loop. The nucleoside triphosphate GTP also activates
      CodY in vitro, but the evidence for activation by GTP in vivo is limited and
      indirect. We constructed a Bacillus subtilis strain (ybgE bcd ywaA) that is
      unable to convert branched-chain alpha-keto acids to ILV or to use ILV as a
      precursor for branched-chain fatty acid synthesis. Unexpectedly, the strain was
      not viable on rich medium. Supplementing rich medium with short, branched-chain
      fatty acids or derepressing expression of genes for de novo ILV synthesis
      bypassed the original lethality, restoring growth and showing that the lack of
      viability was due to insufficient intracellular production of the precursors of
      branched-chain fatty acids. Spontaneous extragenic suppressor mutants that arose
      in the triple mutant population proved to have additional mutations in guaA or
      guaB or codY. Expression of ILV biosynthetic genes in codY mutants was increased.
      The gua mutations caused guanine/guanosine auxotrophy and led to partial
      derepression of direct CodY-repressed targets, including ILV biosynthetic genes,
      under conditions similar to those that caused the original lethality. We conclude
      that a guanine derivative, most likely GTP, controls CodY activity in vivo.

PMID- 21856857
TI  - Structure and host recognition of serotype 13 glycopeptidolipid from
      Mycobacterium intracellulare.
AB  - The Mycobacterium avium-M. intracellulare complex (MAIC) is divided into 28
      serotypes by a species-specific glycopeptidolipid (GPL). Previously, we clarified
      the structures of serotype 7 GPL and two methyltransferase genes (orfA and orfB)
      in serotype 12 GPL. This study elucidated the chemical structure, biosynthesis
      gene, and host innate immune response of serotype 13 GPL. The oligosaccharide
      (OSE) structure of serotype 13 GPL was determined to be 4-2'-hydroxypropanoyl
      amido-4,6-dideoxy-beta-hexose-(1 -> 3)-4-O-methyl-alpha-L-rhamnose-(1 -> 3)-alpha
      L-rhamnose-(1 -> 3)-alpha-L-rhamnose-(1 -> 2)-alpha-L-6-deoxy-talose by using
      chromatography, mass spectrometry, and nuclear magnetic resonance (NMR) analyses.
      The structure of the serotype 13 GPL was different from those of serotype 7 and
      12 GPLs only in O-methylations. We found a relationship between the structure and
      biosynthesis gene cluster. M. intracellulare serotypes 12 and 13 have a 1.95-kb
      orfA-orfB gene responsible for 3-O-methylation at the terminal hexose, orfB, and
      4-O-methylation at the rhamnose next to the terminal hexose, orfA. The serotype
      13 orfB had a nonfunctional one-base missense mutation that modifies serotype 12
      GPL to serotype 13 GPL. Moreover, the native serotype 13 GPL was multiacetylated
      and recognized via Toll-like receptor 2. The findings presented here imply that
      serotypes 7, 12, and 13 are phylogenetically related and confirm that acetylation
      of the GPL is necessary for host recognition. This study will promote better
      understanding of the structure-function relationships of GPLs and may open a new
      avenue for the prevention of MAIC infections.

PMID- 21856858
TI  - High-level gene cassette transcription prevents integrase expression in class 1
      integrons.
AB  - Class 1 integrons are widespread genetic elements responsible for dissemination
      of antibiotic resistance among Gram-negative bacteria. Integrons allow bacteria
      to capture and express gene cassettes (GCs) via an integrase (IntI1) and a
      promoter (Pc) contained in the integron functional platform. GCs are transcribed
      from Pc, of which 13 variants of different strengths have been described, or,
      occasionally, from both Pc and a second promoter (P2). The intI1 promoter
      (PintI1) is repressed by LexA, which is the transcriptional repressor of the
      global regulatory SOS response network. Moreover, PintI1 lies face to face with
      Pc and overlaps P2, both configurations being propitious to transcriptional
      interference (TI). In this study, we analyzed possible transcriptional
      interference by quantifying transcripts produced from Pc, P2, and PintI1. We
      found that the Pc promoter interferes with the level of intI1 transcription but
      that this effect depends on the Pc variant: the strong Pc variant prevents intI1
      expression, in contrast to the other variants. Although P2 formation results in
      LexA binding site disruption and thus prevents SOS regulation of intI1
      expression, P2 does not interfere with PintI1. These findings reveal a tight
      relationship between GC and integrase expression.

PMID- 21856859
TI  - Differential roles of unsaturated and saturated fatty acids on autophagy and
      apoptosis in hepatocytes.
AB  - Fatty acid-induced lipotoxicity plays a critical role in the pathogenesis of
      nonalcoholic liver disease. Saturated fatty acids and unsaturated fatty acids
      have differential effects on cell death and steatosis, but the mechanisms
      responsible for these differences are not known. Using cultured HepG2 cells and
      primary mouse hepatocytes, we found that unsaturated and saturated fatty acids
      differentially regulate autophagy and apoptosis. The unsaturated fatty acid,
      oleic acid, promoted the formation of triglyceride-enriched lipid droplets and
      induced autophagy but had a minimal effect on apoptosis. In contrast, the
      saturated fatty acid, palmitic acid, was poorly converted into triglyceride
      enriched lipid droplets, suppressed autophagy, and significantly induced
      apoptosis. Subsequent studies revealed that palmitic acid-induced apoptosis
      suppressed autophagy by inducing caspase-dependent Beclin 1 cleavage, indicating
      cross-talk between apoptosis and autophagy. Moreover, our data suggest that the
      formation of triglyceride-enriched lipid droplets and induction of autophagy are
      protective mechanisms against fatty acid-induced lipotoxicity. In line with our
      in vitro findings, we found that high-fat diet-induced hepatic steatosis was
      associated with autophagy in the mouse liver. Potential modulation of autophagy
      may be a novel approach that has therapeutic benefits for obesity-induced
      steatosis and liver injury.

PMID- 21856860
TI  - Effects of varenicline on the reinforcing and discriminative stimulus effects of
      cocaine in rhesus monkeys.
AB  - Varenicline is a low-efficacy, alpha4beta2* subtype-selective nicotinic
      acetylcholine receptor (nAChR) agonist that has shown success in smoking
      cessation and promise in preclinical assessments relating to other drugs of
      abuse. The primary goal of the present study was to examine the effects of
      varenicline on cocaine self-administration and cocaine discrimination and compare
      these effects with those of the nAChR agonist nicotine and antagonist
      mecamylamine. One limitation of agonist treatments is the potential for abuse.
      Thus, a second goal was to examine the abuse potential of varenicline in rhesus
      monkeys. In the first experiment, rhesus monkeys (n = 3) were trained to self
      administer cocaine (saline, 0.01-0.56 mg/kg) under a progressive-ratio schedule
      of reinforcement; monkeys also earned all of their food by responding on another
      lever under a fixed-ratio 50 schedule of reinforcement. Chronic administration of
      varenicline (0.01-0.56 mg/kg p.o., salt) potentiated the reinforcing effects of
      cocaine, whereas mecamylamine (0.3-1.7 mg/kg p.o, i.m., i.v., salt) had no
      significant effects on cocaine self-administration up to doses that disrupted
      food-maintained responding. Neither varenicline (0.01-0.17 mg/kg, salt) nor
      nicotine (0.01-0.1 mg/kg, base) functioned as reinforcers when substituted for
      cocaine. Finally, in monkeys trained to discriminate self-administered 0.3 mg/kg
      cocaine, varenicline (0.1-0.3 mg/kg i.v.) did not substitute for cocaine but,
      along with mecamylamine (0.3-1.7 mg/kg i.v.) and nicotine (0.03-0.1 mg/kg i.v.),
      potentiated the discriminative stimulus effects of cocaine. These results suggest
      that varenicline has low abuse liability in monkey models of cocaine abuse, but
      would not be an effective medication for cocaine addiction.

PMID- 21856862
TI  - Retraction. Potti A, Bild A, Dressman HK, Lewis DA, Nevins JR, Ortel TL. Gene
      expression patterns predict phenotypes of immune-mediated thrombosis. Blood.
      2006;107(4):1391-1396.

PMID- 21856861
TI  - Characterization of neuroprotective effects of biphalin, an opioid receptor
      agonist, in a model of focal brain ischemia.
AB  - Approximately 795,000 people experience a new or recurrent stroke in the United
      States annually. The purpose of this study was to assess the protective effect of
      a nonselective opioid receptor agonist, biphalin, in brain edema and infarct
      damage by using both in vitro and in vivo models of stroke. In an in vivo model
      of ischemia, biphalin significantly decreased edema (66.6 and 58.3%) and infarct
      (52.2 and 56.4%) ratios in mouse transient (60-min occlusion/24-h reperfusion)
      and permanent (6 h) middle cerebral artery occlusion models, respectively.
      Biphalin administration also showed decreased neurodegeneration in hippocampal,
      cortical, and striatal brain tissue after ischemia, evidenced by reduced Fluoro
      Jade C staining. In addition, biphalin improved neurological function after
      stroke injury evidenced by neurological score and locomotor activity evaluation.
      Biphalin significantly decreased penumbral expression of Na(+), K(+), 2Cl(-)
      cotransporter (NKCC) and the translocation of the conventional isoforms of
      protein kinase C (PKC). It also reversed the activation of PKC-induced cell
      volume increase during ischemia in primary neuronal cell cultures exposed to 1 h
      of oxygen glucose deprivation. These data suggest that opioid receptor activation
      provides neuroprotection during stroke, and a possible explanation of this
      mechanism could be the inhibition of NKCC function via the regulation of PKC
      dependent cell signaling.

PMID- 21856863
TI  - Noninvasive bioluminescent imaging of primary patient acute lymphoblastic
      leukemia: a strategy for preclinical modeling.
AB  - The efficient engraftment in immune-deficient mice achieved with both acute
      lymphoblastic leukemia (ALL) cell lines and primary samples has facilitated
      identification of the antileukemia activity of a wide variety of agents. Despite
      widespread usage, however, little is known about the early ALL localization and
      engraftment kinetics in this model, limiting experimental read-outs primarily to
      survival and endpoint analysis at high disease burden. In this study, we report
      that bioluminescent imaging can be reproducibly achieved with primary human ALL
      samples. This approach provides a noninvasive, longitudinal measure of leukemia
      burden and localization that enhances the sensitivity of treatment response
      detection and provides greater insight into the mechanism of action of
      antileukemia agents. In addition, this study reveals significant cell line- and
      species-related differences in leukemia migration, especially early in expansion,
      which may confound observations between various leukemia models. Overall, this
      study demonstrates that the use of bioluminescent primary ALL allows the
      detection and quantitation of treatment effects at earlier, previously
      unquantifiable disease burdens and thus provides the means to standardize and
      expedite the evaluation of anti-ALL activity in preclinical xenograft studies.

PMID- 21856864
TI  - Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17
      transcription factor T-bet and RORgammat in mice.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is effective therapy for
      hematologic malignancies through T cell-mediated GVL effects. However, HCT
      benefits are frequently offset by the destructive GVHD, which is also induced by
      donor T cells. Naive Th can differentiate into Th1 and Th17 subsets and both can
      mediate GVHD after adoptive transfer into an allogeneic host. Here we tested the
      hypothesis that blockade of Th1 and Th17 differentiation is required to prevent
      GVHD in mice. T cells with combined targeted disruption of T-bet and RORgammat
      have defective differentiation toward Th1 and Th17 and skewed differentiation
      toward Th2 and regulatory phenotypes, and caused ameliorated GVHD in a major MHC
      mismatched model of HCT. GVL effects mediated by granzyme-positive CD8 T cells
      were largely preserved despite T-bet and RORgammat deficiency. These data
      indicate that GVHD can be prevented by targeting Th1 and Th17 transcription
      factors without offsetting GVL activity.

PMID- 21856865
TI  - Distribution, function, and prognostic value of cytotoxic T lymphocytes in
      follicular lymphoma: a 3-D tissue-imaging study.
AB  - CD8+ CTLs are thought to play a role in the control of follicular lymphoma (FL).
      Yet, the link between CTL tissue distribution, activation status, ability to kill
      FL cells in vivo, and disease progression is still elusive. Pretreatment lymph
      nodes from FL patients were analyzed by IHC (n = 80) or by 3-color confocal
      microscopy (n = 10). IHC revealed a rich infiltrate of CD8+ granzyme B+ (GrzB)
      cells in FL interfollicular spaces. Accordingly, confocal microscopy showed an
      increased number of CD3+CD8+GrzB+ CTLs and a brighter GrzB staining in individual
      CTL in FL samples compared with reactive lymph nodes. CTLs did not penetrate
      tumor nodules. In 3-dimensional (3-D) image reconstructions, CTLs were detected
      at the FL follicle border where they formed lytic synapse-like structures with FL
      B cells and with apoptotic cells, suggesting an in situ cytotoxic function.
      Finally, although GrzB expression in CTLs did not correlate with risk factors,
      high GrzB content correlated with prolonged progression free-survival (PFS) after
      rituximab-combined chemotherapy. Our results show the recruitment of armed CTLs
      with a tumor-controlling potential into FL lymph nodes and suggest that CTL
      associated GrzB expression could influence PFS in FL patients having received
      rituximab-combined chemotherapy.

PMID- 21856867
TI  - Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of
      prior rituximab: results from the phase 2 international study.
AB  - Ofatumumab, the human CD20 monoclonal antibody that binds a distinct epitope from
      rituximab, has demonstrated clinical benefit as monotherapy for patients with
      chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab (FA-ref)
      and patients refractory to fludarabine with bulky (> 5 cm) lymph nodes (BF-ref).
      To potentially gain insight into outcomes in patients previously treated with or
      refractory to rituximab, we performed an ad hoc retrospective analysis in the
      final 96 FA-ref and 111 BF-ref patients. There were 117 patients previously
      treated with rituximab (98 rituximab-refractory); 89 patients were rituximab
      naive. For rituximab-treated, rituximab-refractory, and rituximab-naive patients,
      overall response rate was 43%, 44%, and 53%; median progression-free survival was
      5.3, 5.5, and 5.6 months; and median overall survival was 15.5, 15.5, and 20.2
      months. There were no significant differences in ofatumumab-related infusion
      reactions, or hematologic or infectious adverse events between subgroups. In
      summary, ofatumumab monotherapy was effective and well tolerated in patients with
      fludarabine-refractory chronic lymphocytic leukemia, including in patients with
      previous rituximab exposure. This trial was registered at www.clinicaltrials.gov
      as #NCT00349349.

PMID- 21856868
TI  - cMyb regulates hematopoietic stem/progenitor cell mobilization during zebrafish
      hematopoiesis.
AB  - The establishment of the HSC pool in vertebrates depends not only on the
      formation and the propagation of these stem cells but also on their proper
      trafficking among the defined hematopoietic organs. However, the physiologic
      mechanisms that regulate HSC mobilization remain elusive. Through analysis of the
      zebrafish cmyb mutant cmyb(hkz3), we show that the suppression of cMyb function
      abrogates larval and adult hematopoiesis, with concomitant accumulation of
      hematopoietic stem/progenitor cells (HSPCs) in their birthplace, the ventral wall
      of the dorsal aorta (VDA). Cell tracking and time-lapse recording reveal that the
      accumulation of HSPCs in cmyb(hkz3) mutants is caused by the impairment of HSPC
      egression from the VDA. Further analysis demonstrates that the HSPC migratory
      defects in cmyb(hkz3) mutants are at least partly because of adversely elevated
      levels of chemokine stromal cell-derived factor 1a (Sdf1a). Our study reveals
      that cMyb plays a hitherto unidentified role in dictating physiologic HSPC
      migration by modulating Sdf1a signaling.

PMID- 21856866
TI  - Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence
      through transcriptional repression of MYC.
AB  - Initial cell surface expression of the pre-B cell receptor induces proliferation.
      After 2 to 5 divisions, however, large pre-BII (Fraction C') cells exit cell
      cycle to become resting, small pre-BII cells (Fraction D). The mechanism by which
      pre-BII cells exit cell cycle, however, is currently unclear. The checkpoint at
      the Fraction C'-D transition is critical for immunoglobulin light chain gene
      recombination and to prevent malignant transformation into acute lymphoblastic
      leukemia. Here we demonstrate that inducible activation of pre-B cell receptor
      signaling induces cell-cycle exit through up-regulation of the transcriptional
      repressor BCL6. Inducible activation of BCL6 downstream of the pre-B cell
      receptor results in transcriptional repression of MYC and CCND2. Hence, pre-B
      cell receptor-mediated activation of BCL6 limits pre-B cell proliferation and
      induces cellular quiescence at the small pre-BII (Fraction D) stage.

PMID- 21856869
TI  - Object co-occurrence serves as a contextual cue to guide and facilitate visual
      search in a natural viewing environment.
AB  - There is accumulating evidence that scene context can guide and facilitate visual
      search (e.g., A. Torralba, A. Oliva, M. S. Castelhano, & J. M. Henderson, 2006).
      Previous studies utilized stimuli of restricted size, a fixed head position, and
      context defined by the global spatial configuration of the scene. Thus, it is
      unknown whether similar effects generalize to natural viewing environments and to
      context defined by local object co-occurrence. Here, with a mobile eye tracker,
      we investigated the effects of object co-occurrence on search performance under
      naturalistic conditions. Observers searched for low-visibility target objects on
      tables cluttered with everyday objects. Targets were either located adjacent to
      larger, more visible "cue" objects that they regularly co-occurred in natural
      scenes (expected condition) or elsewhere in the display, surrounded by unrelated
      objects (unexpected condition). Mean search times were shorter for targets at
      expected locations as compared to unexpected locations. Additionally, context
      guided eye movements, as more fixations were directed toward cue objects than
      other non-target objects, particularly when the cue was contextually relevant to
      the current search target. These results could not be accounted for by image
      saliency models. Thus, we conclude that object co-occurrence can serve as a
      contextual cue to facilitate search and guide eye movements in natural
      environments.

PMID- 21856870
TI  - Compressive myelopathy associated with ectasia of the vertebral and spinal
      arteries in a dog.
AB  - A 4-year-old dog was presented for acute, progressive tetraparesis and cervical
      hyperesthesia. Symmetrical tubular structures coursing along the lateroventral
      aspects of the spinal cord at the fourth and fifth cervical vertebrae were
      identified in magnetic resonance images. At necropsy, vertebral arteries and
      their spinal branches were severely ectatic bilaterally, and the cervical spinal
      cord was compressed. Histologically, the ectatic branches of the vertebral and
      ventral spinal arteries were surrounded by fibrosis with scant mononuclear cell
      infiltrates and hemorrhage. Spinal branches of the vertebral arteries had focally
      severe reduction in the tunica media. A thrombus was in an arterial branch.
      Smaller vessels in adjacent tissue had fibrinoid degeneration. Axonal
      degeneration was detected in the affected spinal cord and nerve roots. The
      segmental degenerative radiculomyelopathy in this dog was attributed to anomalous
      ectasia of the vertebral and ventral spinal arteries.

PMID- 21856871
TI  - Acantholytic folliculitis and epidermitis associated with Staphylococcus hyicus
      in a line of white Leghorn laying chickens.
AB  - Several mature Leghorn-type hens with the same genetic background experienced
      skin and feather problems in a breeder flock. There was almost-total feather loss
      on the head and neck, as well as thickened, scaly skin, and follicular ostia were
      plugged with keratin debris. Other individuals exhibited prominent subcutaneous
      nodules multifocally on the head. Histologic examination of the skin revealed a
      severe hyperplasia of follicular epithelium with hyperkeratosis and cystic
      dilation. Numerous clefts and vesicles were detected along the epidermis and
      follicular epithelium, some containing acantholytic keratinocytes. A mild
      heterophilic inflammation was associated with these lesions, and few gram
      positive cocci were present in the keratin plugs. Bacterial culture of the skin
      yielded a variable amount of Staphylococcus hyicus. Immunochemistry looking for
      chicken IgY revealed no intercellular staining in the epidermis or follicular
      epithelium. All these findings supported a diagnosis of Staphylococcus-associated
      acantholytic epidermitis and folliculitis. This case suggests that S. hyicus
      could be a significant pathogen in poultry production. The close genetic
      relationship among affected individuals could indicate a hereditary
      predisposition in this line of White Leghorn laying chickens.

PMID- 21856875
TI  - Why do children with down syndrome have subnormal vision?
AB  - PURPOSE: Explore characteristics of Down syndrome to find causes of subnormal
      vision. Explore vision studies to find patterns of decreased vision. RESULTS:
      Some obvious potential causes are nystagmus and high refractive error; however,
      nystagmus and high refractive errors are not a guarantee of poor vision.
      Accommodative insufficiency is often present, compromising near vision. Vision
      studies are difficult to compare mainly because of differences in determining and
      correcting refractive errors. Sweep visually evoked potentials (sVEP) require
      little effort from the patient and have shown near normal vision in infancy, with
      improvement leveling off at age 12 to 24 months without further improvement.
      CONCLUSIONS: People with Down syndrome have a wide variation in visual acuity,
      but generally 20 / 40 or worse. Both the eye and brain tend to be different in
      these patients compared to age matched normal subjects. Also, accommodative
      insufficiency (determined by dynamic retinoscopy) is often present in children
      Down syndrome, making bifocals a necessary consideration.

PMID- 21856876
TI  - Intermittent exotropia: facts, opinions, and unknowns.
AB  - INTRODUCTION: Intermittent exotropia (IXT) can be a controversial topic, often
      eliciting lively discussion. This lecture will discuss its definition, incidence,
      age of onset, presentation, natural variation, criteria for deterioration, goals
      of treatment, effectiveness of surgical treatment, types of surgical treatment,
      and unwanted effects of surgical treatment. METHOD: Results from the scientific
      literature, opinions of respected colleagues, the opinion of the author, and the
      results of live polling of the audience during the John Pratt-Johnson lecture are
      presented. RESULTS: IXT is defined as an exotropia that is present intermittently
      predominantly for distance. Its incidence is about 1% and it usually has an onset
      before age 5. Patients often present because of concern regarding the appearance
      of the eye misalignment. There is natural variation in the control of IXT, the
      angle of IXT, and the amount of stereopsis. Criteria that denote deterioration
      are increasing frequency of IXT, progressively and consistently increasing angle
      of IXT, loss of binocular vision, and increasing concern regarding the patient's
      appearance and its effect on social interaction. Goals of treatment are to retain
      equal or nearly equal vision, to obtain acceptable cosmesis, and to retain
      binocular vision. The long-term success of surgical treatment is not well proven.
      Persistent postoperative overcorrection is an unwanted effect of surgical
      treatment. CONCLUSION: The inherent biologic variation that occurs when measuring
      the components of IXT makes it difficult to be dogmatic about IXT, particularly
      when trying to decide when deterioration is occurring.

PMID- 21856877
TI  - Incomitant strabismus: does extraocular muscle form denote function?
AB  - The paradigm that an underacting extraocular muscle (EOM) is always atrophic or
      hypoplastic, and an overacting EOM should always be enlarged, leads to
      inconsistencies with clinical observations. It is inconsistent with the findings
      of normal extraocular muscle diameters in patients with apparent superior oblique
      muscle palsy, "overacting" inferior oblique muscles, and the superior rectus
      muscle overaction / contracture syndrome, among other clinical entities. These
      inconsistencies can be reconciled if one accepts the possibility that EOM
      contractile activity may reflect a change in neural input to an anatomically
      normal muscle, and / or that muscle contractile activity may be altered by a
      shift in fiber type and distribution within a normal-sized muscle. This
      remodeling may occur as a result of vergence adaptation or any change in neural
      stimulus to the muscle. There is substantial evidence to suggest that both these
      theoretical possibilities may likely occur.

PMID- 21856878
TI  - Conservative management of intermittent distance exotropia: a review.
AB  - BACKGROUND AND PURPOSE: Intermittent distance exotropia is difficult to
      conservatively manage, with techniques varying widely between institutions. This
      review aims to examine current literature on conservative management for
      intermittent distance exotropia, investigate its impact upon current clinical
      practice, and identify areas for further research. METHOD: A literature search
      was performed using PubMed, Web of Knowledge, LILACS, and the University of
      Liverpool Orthoptic Journals and Conference Transactions Database. All English
      language papers published between 1950 and the present day were considered.
      RESULTS: Intermittent distance exotropia is a difficult condition to manage
      because of its variability / uncertain natural history, although control scores
      can facilitate management decisions. Research is required to establish
      recommended dosages for antisuppression occlusion and determine whether other
      treatments such as minus lenses are more effective. Use of orthoptic exercises
      has declined, but recently certain exercises have been shown to improve surgical
      outcomes if applied preoperatively. Prisms are mainly used postoperatively. Minus
      lens therapy is recommended as a first line treatment, but may not always be
      successful. CONCLUSION: Conservative management techniques for intermittent
      distance exotropia have their place as both an alternative and an adjunct to
      surgery. However, further research needs to be conducted to determine which
      techniques are appropriate for which patients.

PMID- 21856879
TI  - The effect of developmentally-at-risk status on the reliability of the iScreen(r)
      photorefractive device in young children.
AB  - INTRODUCTION AND PURPOSE: We evaluated the impact of developmentally-at-risk
      status on the results of photorefractive screening with iScreen(r). PATIENTS AND
      METHODS: We sequentially recruited 169 children (aged 2-5 years) to participate
      in a blinded, prospective study of a photoscreening device. The principle
      investigator examined the children after photoscreening. Using established
      standards for amblyogenic factors, the principle investigator and photoscreen
      interpreters separately made a determination of "normal" or "needs referral" for
      each child. Sensitivity, specificity, positive predictive value, and negative
      predictive value for the photoscreening device were determined. RESULTS: Overall,
      sensitivity was 85% with a positive predictive value of 98%, and specificity was
      87% with a negative predictive value of 47%. Developmentally-at-risk status in 34
      children (three refused imaging) did not reduce sensitivity (89%) or specificity
      (100%) when compared with 130 children (two refused imaging) who did not have
      developmentally-at-risk factors (sensitivity = 84% and specificity = 80%).
      CONCLUSION: The efficacy of photorefractive screening in young children with
      developmentally-at-risk status is comparable to results found in normal children.

PMID- 21856880
TI  - Can a photoscreener help us remotely evaluate and manage amblyopia?
AB  - INTRODUCTION AND PURPOSE: To determine whether the plusoptiX(r) S04 photo
      screener can assist in remotely managing amblyopia. METHODS: A retrospective
      chart review was performed on 103 children with amblyopia. All patients had a
      plusoptiX(r) screening performed while wearing their optical correction during a
      comprehensive pediatric ophthalmology examination. RESULTS: Children were
      classified as being fully treated in their glasses or needing further
      intervention to treat their amblyopia and / or strabismus. Further treatment was
      indicated if children were found to have abnormal alignment and / or best
      corrected visual acuity of 20 / 40 or worse in either eye with correction.
      Photoscreening results for these children demonstrated a sensitivity,
      specificity, false negative rate and false positive rate of 69%, 84%, 31%, and
      16%, respectively. When visual acuity and photoscreening were combined for
      children who initially passed the plusoptiX(r) screen, these metrics improved to
      97%, 89%, 2.7%, and 11%, respectively. CONCLUSION: Photoscreening combined with
      simple measurements of visual acuity may be a viable option for following
      efficacy of treatment in amblyopes. In some parts of the United States and in
      many areas of the world where telemedicine plays an increasingly important role,
      the plusoptiX(r) photoscreener could enhance vision care and may enhance
      telemedicine and the treatment of amblyopia.

PMID- 21856881
TI  - Factors contributing to the outcome of sensory testing in patients with anomalous
      binocular correspondence.
AB  - Traditional teaching on anomalous retinal correspondence (ARC) identifies the
      dissociative quality of a sensory test as the primary factor influencing the
      outcome of correspondence testing. However, these tests differ also in function
      and format. This study compared one mildly dissociating test and one highly
      dissociating test to evaluate the subjective visual direction of both the
      deviation point and the fovea of the deviating eye in 74 patients with ARC.
      Subjects were more likely to demonstrate an ARC response, and to do so after a
      significantly shorter period of time following change in alignment, on the
      minimally dissociating tests. Eighty-five percent demonstrated the presence of a
      pseudo-fovea at the deviation point, while only 39% had evidence of rewiring of
      the deviated fovea. The mean angle of deviation of the latter group was
      significantly larger than that of the former group (P < 0.001). Exotropic
      patients were more likely to rewire the fovea than esotropic patients (P <
      0.005). The mean time needed to rewire a pre-existing ARC following a change in
      deviation was 7.7 +/- 1 months. Results of this study indicate that variables
      influencing sensory test results include: a) retinal element evaluated, b)
      magnitude of the deviation, c) direction of the deviation, and d) age of onset of
      the strabismus. Results of sensory testing in patients with ARC may be
      misinterpreted if these factors are not taken into consideration.

PMID- 21856882
TI  - Idiopathic convergence paralysis: a rare case.
AB  - Convergence paralysis is a rare entity that is usually associated with head
      trauma or mid-brain pathology. We describe a patient with idiopathic convergence
      paralysis that resolved without intervention. Idiopathic convergence paralysis is
      very rare and does not satisfy the criteria for diagnosis as described by
      Bielschowsky in 1936. Furthermore, this case demonstrates the possibility of
      spontaneous resolution of convergence paralysis.

PMID- 21856883
TI  - Historical vignette: Eduard Hummelsheim (1868-1952): ophthalmologist and pioneer
      of transposition surgery.

PMID- 21856885
TI  - An investigation into the social context of low-income, urban Black and Latina
      women: implications for adherence to recommended health behaviors.
AB  - Understanding factors that promote or prevent adherence to recommended health
      behaviors is essential for developing effective health programs, particularly
      among lower income populations who carry a disproportionate burden of disease. We
      conducted in-depth qualitative interviews (n = 64) with low-income Black and
      Latina women who shared the experience of requiring diagnostic follow-up after
      having a screening mammography with abnormal findings. We found that in addition
      to holding negative and fatalistic cancer-related beliefs, the social context of
      these women was largely defined by multiple challenges and major life stressors,
      factors that may interfere with their ability to attain health. Factors commonly
      mentioned included competing health issues, economic hardship, demanding
      caretaking responsibilities and relationships, insurance-related challenges,
      distrust of health care providers, and inflexible work policies. Black women also
      reported discrimination and medical mistrust, whereas Latinas experienced
      difficulties associated with immigration and social isolation. These results
      suggest that effective health interventions not only address change among
      individuals but must also change health care systems and social policies in order
      to reduce health disparities.

PMID- 21856886
TI  - Fibroblast growth factor 21, ketogenic diets, and insulin resistance.

PMID- 21856887
TI  - Less is more? Is permissive underfeeding in critically ill patients necessary?

PMID- 21856888
TI  - A lack of epidemiologic evidence to link consumption of monosodium L-glutamate
      and obesity in China.

PMID- 21856889
TI  - Microarray analysis reveals genes and functional networks relevant to the
      predisposition to inverted teats in pigs.
AB  - The inverted teat defect is characterized by the failure of teats to protrude
      from the udder surface and has a negative effect on the economic efficiency of
      pig production. The inverted teat defect is influenced by genetic factors, but
      the number and identity of relevant genes are unknown. In this study, we compared
      the mRNA expression of teat tissues from unaffected pigs and affected pigs by
      using microarrays. Simultaneously, 24,123 probe sets were screened, of which some
      15,000 had present calls and were analyzed for differential expression between
      mesenchymal and epithelial tissue of 3 categories of teats (i.e., normal teats of
      unaffected and affected animals, and inverted teats of the latter). Differential
      expression was more pronounced in epithelial than in mesenchymal tissue, and the
      comparisons among the 3 categories of teats showed that local processes at the
      side of the affected area as well as processes taking place at the level of the
      organ contribute to the development of inverted teats. Genes related to
      biofunctions of cell maintenance, proliferation, differentiation, and
      replacement; organismal, organ, and tissue development; genetic information and
      nucleic acid processing; and cell-to-cell signaling and interaction were
      differentially expressed, depending on the teat phenotype and the status of the
      animal as affected or unaffected. In particular, genes encoding members of
      canonical pathways of growth factor signaling were highlighted. Complementary to
      previous real-time quantitative reverse-transcription PCR experiments showing
      upregulation of growth factors (epidermal growth factor, fibroblast growth
      factor, hepatocyte growth factor, platelet-derived growth factor, vascular
      endothelial growth factor) and their receptors in the inverted teat, here it is
      shown that the abundance of transcripts encoding subordinated proteins (acid
      phosphatase 1, soluble; activating transcription factor 2; casein kinase 2, alpha
      1 polypeptide; casein kinase 2, alpha prime polypeptide; actinin, alpha 2; and
      Homo sapiens growth factor receptor-bound protein 2) within the growth factor
      signaling pathways are also affected. Tuning of the expression of genes of these
      pathways balances the differentiation and proliferation of epithelial and
      mesenchymal teat tissue and finally affects the shape and structure of the teats.

PMID- 21856890
TI  - Effect of sow history features on growth and feed intake in grow-finish pigs.
AB  - The sow provides a specific environment to her offspring during gestation and
      lactation. Certain features in the early life of the sow (sow history features)
      may affect her ability to deliver and feed a healthy litter. In genetic analyses
      of grow-finish traits, these effects are estimated as common litter or permanent
      sow effects. The objective of this research was to identify sow history features
      that affect the growth rate (GR) and feed intake (FI) of her offspring during the
      grow-finish stage. Data from 17,743 grow-finish pigs, coming from 604 sires and
      681 crossbred sows, were recorded between May 2001 and February 2010 at the
      experimental farm of the Institute for Pig Genetics (Beilen, the Netherlands).
      The grow-finish stage was divided into 2 phases (phase 1: 26 to 75 kg; phase 2:
      75 to 115 kg). The sow history features were birth litter size, birth year and
      season, birth farm, weaning age, age of transfer to the experimental farm, and
      age at first insemination. The sow features were added to the basic model one at
      a time to study their effect on the grow-finish traits of the pigs. Subsequently,
      significant sow features (P < 0.1) were fitted simultaneously in an animal model.
      With every extra piglet in the birth litter of the sow, the GR of her offspring
      decreased by 1 g/d and the FI decreased by 4 g/d. Every extra day to the first
      insemination increased the GR of grow-finish pigs by 0.1 g/d. The heritability
      estimates for GR and FI (only in phase 2 of the grow-finish stage) decreased
      after adding the sow features to the model. No differences were found in
      estimates of the common litter effects between the basic model and the model with
      all significant sow features. The estimates of the permanent sow effect changed
      for FI from 0.03 (basic model) to 0.00 (model with sow features), and for FI in
      phase 1, the permanent sow effect decreased from 0.03 (basic model) to 0.01
      (model with sow features). In conclusion, selected sow features do affect the
      grow-finish traits of the pigs, but their estimates are small and explain only a
      small proportion of the differences in the GR and FI of grow-finish pigs. The sow
      features partially explained the permanent sow effect of FI-related traits and
      did not explain the common litter effect. Although the sow early life features
      can affect piglet traits, they do not predict which sows produce better
      performing offspring in the grow-finish stage.

PMID- 21856891
TI  - Nutrient mass balance and performance of feedlot cattle fed corn wet distillers
      grains plus solubles.
AB  - Two experiments using 96 steers each were conducted to evaluate the effect of
      corn wet distillers grains plus solubles (WDGS) concentration on steer
      performance, N loss, and P mass balance. Feeding WDGS as an energy source instead
      of protein may increase N release into the environment but also the amount of N
      removed in the manure. Calves (BW = 294 +/- 33 kg) were fed 167 d from November
      to May (WIN), and yearlings (BW = 373 +/- 24 kg) were fed 133 d from June to
      October (SUM). Treatments consisted of 0, 15, and 30% dietary inclusion of WDGS
      (DM basis) replacing corn (CON, 15WDGS, 30WDGS, respectively). Basal diets
      consisted of high-moisture and dry-rolled corn fed at a 1:1 ratio, 7.5% alfalfa
      hay, 5% molasses, and 5% supplement (DM basis). The CON and 15WDGS diets were
      formulated to meet MP requirements, and 30WDGS exceeded MP requirements. Dry
      matter intake, ADG, and HCW increased linearly (P < 0.05) with WDGS concentration
      in the WIN, whereas DMI and ADG increased linearly (P < 0.10) in the SUM.
      Efficiency of BW gain was not different (P > 0.10) among treatments in either
      experiment. Nitrogen and P intake increased linearly (P < 0.01) with WDGS
      concentration in both experiments. Calculated retention of N and P increased
      linearly (P <= 0.05) with WDGS concentration in the WIN but not in the SUM (P >
      0.10). Calculated excretion of N and P increased linearly (P < 0.01) with WDGS
      concentration in both experiments. Amount of N removed in the manure was not
      different (P = 0.26) among treatments in the WIN but increased linearly (P =
      0.05) with WDGS concentration in the SUM. Amount of P and OM removed increased
      linearly (P <= 0.05) with WDGS concentration in both experiments. Amount of N
      lost (kg/steer) increased linearly (P < 0.05) with WDGS concentration in both
      experiments. Expressed as a percentage of N excretion, N volatilization rate
      (amount of N lost divided by N excretion) was not different (P > 0.30) among
      treatments and averaged 68.3 and 77.0 in the WIN and SUM, respectively. More N
      volatilized when WDGS were fed, but not all of the additional N excreted was
      volatilized. Regressing the amount of OM on the pen surface against manure N, 98%
      of the variability for manure N in the WIN and 92% in the SUM was accounted for.
      Feeding WDGS increased the total amount of N lost to volatilization; however, not
      all of the additional N excreted was lost because of an increase in the
      proportion of manure OM.

PMID- 21856892
TI  - The forage type (grazing versus hay pasture) fed to ewes and the lamb sex affect
      fatty acid profile and lipogenic gene expression in the longissimus muscle of
      suckling lambs.
AB  - Meat intramuscular fat (IMF) contributes to meat quality and consumer acceptance.
      Molecular events that occur during IMF deposition and the identification of genes
      that are differentially expressed during this process are important to the design
      of an optimal nutrition plan for animals. In the present study, we examined the
      effect of the forage type (grazing vs. hay pasture) fed to ewes and the effect of
      lamb sex on the LM fatty acid (FA) profile and gene expression of suckling lambs
      (10 to 12 kg of BW at slaughter); ewes received pasture hay (PH) or grazed
      pasture (GRE). Forage type had a significant effect on IMF FA profile. Ewes
      grazing green forage (GRE) promoted the formation and deposition of vaccenic acid
      (C18:1n-7), CLA, and PUFA n-3 in LM from their suckling lambs (P < 0.05). We
      found that forage type affected the expression of the sterol regulatory element
      binding transcription factor 1 (SREBF1) gene in females. However, in males, it
      modulated stearoyl CoA desaturase (SCD) gene expression (P < 0.05). Moreover, our
      results showed that females, independent of the diet of the ewes (PH or GRE), are
      predisposed to develop fat and to upregulate the expression of key genes of
      transcriptional factors PPARA, CEBPB, SREBF1, and lipoprotein lipase (LPL) and
      SCD (P < 0.05). The data suggest that SREBF1, SCD, and most likely CEBPB gene
      expression in young suckling lambs is modulated by both lamb sex and forage type
      fed to ewes. Fatty acid indicators PUFA, n-6/n-3, CLA, and SFA are closely
      related to LPL, SCD, PPARA, and CEBPB gene expression depending on animal sex or
      the diet of ewes. This study suggests that grazing pasture affects FA composition
      promoting greater vaccenic, CLA, and total PUFA n-3 FA in female and male
      suckling lambs, and it is mediated through the regulation of lipogenic enzyme
      expression.

PMID- 21856893
TI  - Integrating bermudagrass into tall fescue-based pasture systems for stocker
      cattle.
AB  - The daily BW gain of stocker steers grazing tall fescue [Lolium arundinaceum
      (Schreb.) S.J. Darbysh. = Schedonorus arundinaceus (Schreb.) Dumort.]-based
      pastures typically declines during summer. To avoid these declines, in part to
      mitigate the effects of tall fescue toxicosis, it is commonly advised to move
      cattle to warm-season forage during this period. A 3-yr (2006, 2007, and 2008)
      grazing study was conducted to evaluate the effect of replacing 25% of the area
      of a tall fescue/clover (81% endophyte-infected) pasture system with "Ozark"
      bermudagrass [Cynodon dactylon (L.) Pers.] overseeded with clover (Trifolium
      spp.) to provide summer grazing for stocker steers (TF+BERM). The TF+BERM
      treatment was compared with a grazing system in which tall fescue/clover (TF)
      pastures were the only type of forage available for grazing. Our objective was to
      determine if replacement of 25% of the land area in a fescue system with
      bermudagrass would increase annual beef production compared with a system based
      solely on tall fescue. The study was conducted at the Southwest Research and
      Education Center of the University of Missouri near Mt. Vernon. Each treatment
      was rotationally stocked with 5 steers (248 +/- 19.3 kg) on 1.7 ha. Fertilizer
      applications were applied at rates recommended for each respective forage
      species. Total forage production, BW gain per hectare, and season-long ADG of
      steers was greater (P < 0.06) for TF+BERM than for TF in 2006, but none of these
      measures differed (P > 0.19) in 2007 or 2008. In vitro true digestibility of
      pastures was greater (P = 0.01) for TF (84.4%, SEM = 0.64%) compared with TF+BERM
      (80.6%, SEM = 0.79%), even in summer. The decreased in vitro true digestibility
      of the bermudagrass pastures likely negated any benefit that animals in TF+BERM
      had in avoiding the ergot-like alkaloids associated with endophyte-infected tall
      fescue. Renovating 25% of the pasture system to bermudagrass provided some
      benefit to the system in years when summertime precipitation was limited (2006)
      but provided no value in wetter years (2007 and 2008). Although renovating
      endophyte-infected tall fescue pastures to a warm-season forage is a widely used
      practice to mitigate tall fescue toxicosis, the benefits of this practice are
      limited if forage quality of the warm season component is poor.

PMID- 21856894
TI  - Lactic acid enhancement can improve the fresh and cooked color of dark-cutting
      beef.
AB  - Two experiments were conducted to compare the effects of enhancing dark-cutting
      (DC) strip loins with lactic acid (LAC) on fresh and cooked beef color, as well
      as sensory attributes, with nonenhanced, normal pH strip loins (CH). Strip loins,
      with an average ultimate pH of 6.70 +/- 0.11 (Exp. 1) and 6.78 +/- 0.11 (Exp. 2),
      were cut into 2 equal-length sections, and DC sections were randomly assigned as
      either nonenhanced DC or DC enhanced with 0.15 (Exp. 1), 0.35 (Exp. 1 and 2), or
      0.50% (Exp. 2) LAC at a target of either 105 (Exp. 1) or 112% (Exp. 2) of the raw
      product weight. Enhancement with 0.15 and 0.35% LAC did not (P > 0.05) affect
      postenhancement pH of DC strip loins when enhanced at a target of 105% (Exp. 1);
      however, postenhancement pH was reduced (P < 0.05) substantially by LAC
      enhancement at 115% of raw product weight, with pH values of DC sections enhanced
      with 0.50% LAC being similar (P > 0.05) to those of CH strip loin sections (Exp.
      2). In Exp. 1, raw steaks from CH strip loins had greater (P < 0.05) a* and b*
      values as well as Japanese beef color scores compared with steaks from
      nonenhanced and LAC-enhanced DC strip loins across the first 3 d of simulated
      retail display (LAC enhancement * retail display duration; P < 0.01). Again in
      Exp. 2, raw steaks from CH sections had greater (P < 0.05) L*, a*, and b* values
      and Japanese color scores than did steaks from DC sections, regardless of LAC
      enhancement; however, mean Japanese color scores of CH steaks were only 0.7 and
      0.4 units greater (P < 0.05) than the color scores of DC steaks enhanced with
      0.35 and 0.50% LAC, respectively. In Exp. 1, CH steaks received the highest (P <
      0.05) cooked color and degree of doneness scores, yet scores for CH steaks and
      steaks from DC sections enhanced with 0.50% LAC did not (P > 0.05) differ when
      cooked to 71 degrees C in Exp. 2. Fresh and cooked color of DC beef was only
      minimally altered when enhanced with 0.35% LAC at 105% of the fresh product
      weight; however, when DC beef was enhanced with 0.35 and 0.50% LAC at a target of
      112%, fresh and cooked color were improved close to that of CH beef. Because the
      persistent red or pink cooked color of DC was virtually eliminated by 0.50% LAC
      enhancement, LAC-enhanced DC beef may be suitable for food-service markets;
      however, the raw or fresh color results of Exp. 2 suggested that the fresh color
      of DC beef can be improved to the color of normal pH beef by postmortem
      acidification, leading to the possible recoupment of most, if not all, of the
      lost value associated with DC beef.

PMID- 21856895
TI  - Effects of adrenocorticotropic hormone and flunixin meglumine on pregnancy
      retention in beef cows.
AB  - Pregnancy loss in beef cattle after d 28 of gestation is variable, but it has
      been reported to be as great as 14% and has been related to transportation or
      handling stress. The primary objective of this study was to determine whether
      activation of the hypophyseal-adrenal axis with ACTH would mimic a stressful
      response and cause pregnancy loss in beef cattle. A secondary objective was to
      determine if a single injection of the PG synthesis inhibitor flunixin meglumine
      would attenuate the stress response and suppress serum PGF(2alpha) concentrations
      to prevent pregnancy loss. Forty nonlactating beef cows that were 34 +/- 0.33 d
      pregnant were used for this study. In a 2 * 3 factorial arrangement, cows were
      randomly assigned to receive ACTH [0 or 0.5 IU/kg of BW, intramuscularly (i.m.)]
      at 0 and 2 h of the study and flunixin meglumine (0, 1.1, or 2.2 mg/kg of BW,
      i.m.) at 0 h. Blood samples were collected from all cows at 0 h and every 30 min
      for 4 h to measure serum cortisol and PGF(2alpha) metabolite (PGFM)
      concentrations. Rectal temperature was collected for each cow at 0, 120, and 240
      min. Pregnancy exams were conducted 31 and 58 d after treatment by transrectal
      ultrasonography, and the presence of a fetal heartbeat was used as an indicator
      of fetal viability. Serum cortisol concentration was affected (P < 0.01) by ACTH,
      time, and the interaction of ACTH * time, but not by flunixin meglumine (P >=
      0.14) or any other interactions. Cortisol concentrations increased (P < 0.01) in
      the serum of ACTH-treated cows immediately after ACTH treatment and remained
      increased (P < 0.01) throughout the 4-h sampling period. Serum PGFM concentration
      was not affected by ACTH (P = 0.97) or by any interactions (P > 0.35) with ACTH,
      but was affected (P < 0.01) by flunixin meglumine, time, and the interaction of
      flunixin meglumine * time. Regardless of dosage (1.1 or 2.2 mg/kg of BW),
      flunixin meglumine decreased (P < 0.01) serum PGFM concentrations in both ACTH
      treated and control cows for the duration of the study. Although ACTH treatment
      induced a prolonged increase in serum cortisol concentration, none of the cows
      used in this study lost a pregnancy. In conclusion, the activation of the
      hypophyseal-adrenal axis with ACTH increased serum cortisol concentrations but
      did not increase serum concentrations of PGFM or cause pregnancy loss during
      early gestation in cows. Flunixin meglumine treatment suppressed serum PGFM
      concentrations in control and ACTH-treated cows.

PMID- 21856896
TI  - Effects of surplus dietary L-tryptophan on stress, immunology, behavior, and
      nitrogen retention in endotoxemic pigs.
AB  - The possible beneficial effects of surplus dietary Trp (+5 g of Trp/kg of diet)
      on factors related to stress, immunology, behavior, and N retention were
      investigated in postweaning piglets (approximately 15 kg of BW) challenged for 10
      d with intravenous bacterial lipopolysaccharide (from Escherichia coli). Two
      diets fed restrictively (732 kJ of NE/kg of BW(0.75)/d) were compared, 1) a basal
      diet (apparent ileal digestible Trp = 1.9 g/kg; the recommended amount of Trp to
      warrant near-optimal growth in nonendotoxemic piglets), and 2) a Trp-enriched
      basal diet (+5 g of free l-Trp/kg), with 8 individually housed piglets per diet.
      Pooled salivary cortisol, but not plasma cortisol sampled at euthanasia, showed a
      tendency (P = 0.07) toward reduced concentrations in the Trp group (1.1 vs. 1.4
      ng/mL; pooled SE = 0.1 ng/mL). Plasma C-reactive protein was reduced (P = 0.04)
      in the Trp group (0.9 vs. 5.0 mg/L; pooled SE = 1.3 mg/L), but haptoglobin, IL-6,
      tumor necrosis factor alpha, and lipopolysaccharide-induced fever were similar
      between the 2 dietary treatments. Physical activity related to approaching a
      human showed a tendency (P = 0.08) toward increased latency time in the Trp group
      (101 vs. 60 s; pooled SE = 16 s), but the times spent standing, sitting, and
      lying were similar between dietary treatments. The ADFI, ADG (346 vs. 302 g/d;
      pooled SE = 14 g/d; P = 0.11), body N retention (11.6 vs. 11.0 g/d; pooled SE =
      0.2 g/d; P = 0.18), and G:F (0.55 vs. 0.49; pooled SE = 0.03; P = 0.17) were not
      different between the groups fed Trp and the basal diet. In conclusion, surplus
      dietary Trp had limited effects on stress, immunology, behavior, and N retention
      in a pig model of systemic endotoxemia.

PMID- 21856897
TI  - Effects of porcine circovirus type 2 vaccine and increasing standardized ileal
      digestible lysine:metabolizable energy ratio on growth performance and carcass
      composition of growing and finishing pigs.
AB  - Four experiments were conducted to examine the effect of porcine circovirus type
      2 (PCV2) vaccination on the response of growing and finishing pigs (PIC 337 *
      1050) to increasing dietary Lys. Experiments 1 and 2 evaluated 38- to 65-kg gilts
      and barrows, respectively, and Exp. 3 and 4 evaluated 100- to 120-kg gilts and
      barrows, respectively. Gilts and barrows were housed separately in different
      barns. Treatments were allotted in a completely randomized design into 2 * 4
      factorials with 2 PCV2 treatments (PCV2-vaccinated and nonvaccinated) and 4
      standardized ileal digestible (SID) Lys:ME ratios (2.24, 2.61, 2.99, and 3.36
      g/Mcal in Exp. 1 and 2 and 1.49, 1.86, 2.23, and 2.61 g/Mcal in Exp. 3 and 4)
      within each experiment. There were 5 pens per treatment. At the start of Exp. 1
      and 2, there were more pigs per pen (P < 0.001) in vaccinated pens because
      vaccinated pigs had a greater survival rate than nonvaccinated pigs, and this
      increase was maintained throughout the experiments. Removal rate approached 30%
      in nonvaccinated barrows and more than 20% in nonvaccinated gilts. Observation
      suggested that the removals were largely due to PCV2-associated disease. No PCV2
      vaccination * SID Lys:ME ratio interactions (P > 0.10) were observed in any of
      the 4 studies. In Exp. 1 and 2, PCV2-vaccinated pigs had increased (P < 0.001)
      ADG compared with nonvaccinated pigs. The growth response was primarily due to
      increases in ADFI, which suggests that vaccinated pigs have a greater Lys
      requirement (g/d) than nonvaccinated pigs. In Exp. 1, increasing the SID Lys:ME
      ratio increased (quadratic; P < 0.04) ADG and G:F, with pigs fed the 2.99 g/Mcal
      ratio having the greatest ADG and G:F. In Exp. 2, increasing the SID Lys:ME ratio
      improved (linear; P < 0.001) G:F. In Exp. 3, ADG and G:F increased (P < 0.05) in
      a quadratic manner as the SID Lys:ME ratio fed increased. In Exp. 4, increasing
      the SID Lys:ME ratio increased ADG (linear; P < 0.001) and G:F (quadratic; P =
      0.03). Although PCV2 vaccination improved growth, the corresponding increase in
      ADFI did not increase the optimal SID Lys:ME ratio for growing and finishing
      barrows and gilts.

PMID- 21856898
TI  - Energy concentration and phosphorus digestibility in whey powder, whey permeate,
      and low-ash whey permeate fed to weanling pigs.
AB  - Two experiments were conducted to determine DE and ME, the apparent total tract
      digestibility (ATTD) of P, and the standardized total tract digestibility (STTD)
      of P in whey powder (3,646 kcal/kg), whey permeate (3,426 kcal/kg), and low-ash
      whey permeate (3,657 kcal/kg) fed to weanling pigs. The DE and ME in the 3 whey
      products were determined using 32 barrows (9.2 +/- 0.4 kg of BW). A basal diet
      based on corn, soybean meal, and fish meal and 3 diets containing 70% of the
      basal diet and 30% of each whey product were prepared. Each diet was fed to 8
      pigs that were housed individually in metabolism cages. The total collection
      method was used for fecal and urine collections with 5-d adaptation and 5-d
      collection periods, and the difference procedure was used to calculate DE and ME
      in the 3 whey products. The concentrations of DE in whey powder and low-ash whey
      permeate were greater (P < 0.001) than in whey permeate (3,646 and 3,683 vs.
      3,253 kcal/kg of DM). The concentrations of ME in whey powder and low-ash whey
      permeate were also greater (P < 0.001) than in whey permeate (3,462 and 3,593 vs.
      3,081 kcal/kg of DM). The ATTD and STTD of P in the 3 whey products were
      determined using 32 barrows (11.0 +/- 0.81 kg of BW). Three cornstarch-sucrose
      based diets containing 30% of each whey product as the sole source of P were
      prepared. A P-free diet that was used to estimate the basal endogenous losses of
      P was also formulated. The ATTD of P in whey powder and in whey permeate was
      greater (P < 0.001) than in low-ash whey permeate (84.3 and 86.1 vs. 55.9%), but
      the STTD values for P were not different among the 3 ingredients (91.2, 93.1, and
      91.8% in whey powder, whey permeate, and low-ash whey permeate, respectively). In
      conclusion, whey permeate contains less GE, DE, and ME than whey powder and low
      ash whey permeate, but all 3 ingredients have an excellent digestibility of P.

PMID- 21856899
TI  - An energy-rich diet enhances expression of Na(+)/H(+) exchanger isoform 1 and 3
      messenger RNA in rumen epithelium of goat.
AB  - Rumen epithelial Na(+)/H(+) exchanger (NHE) catalyzes the exchange of
      extracellular Na(+) for intracellular H(+). Thus, it is of importance in the
      maintenance of Na and pH homeostasis of rumen epithelial cells. We have tested
      the hypothesis that an increase in energy and protein intake induces alterations
      of NHE isoform 1, 2, and 3 (NHE1, NHE1, and NHE3, respectively) mRNA abundance in
      the rumen epithelium of goats. Goats (n = 26) were randomly allocated to 2
      experiments (n = 16 in Exp. 1, and n = 10 in Exp. 2) and fed either peanut straw
      ad libitum [PNS, n = 8 in Exp. 1, and n = 5 in Exp. 2; 600 kJ of ME/(kg(0.75).d)]
      or PNS + concentrate [CF, n = 8 in Exp. 1, and n = 5 in Exp. 2; 1,000 kJ of
      ME/(kg(0.75).d)] for 42 d. Concentrate (400 g/d) was given daily (0800 to 1700 h)
      in 4 equal portions at 3-h intervals. In Exp. 1, the goats were euthanized 2 h
      after the last portion of concentrate was fed, and in Exp. 2, the goats were
      euthanized after a fasting period of 16 h. In Exp. 1, goats in the CF treatment
      exhibited a greater ruminal short-chain fatty acid (SCFA) concentration (140.6 +/
      1.30 mM) compared with those in the PNS treatment (114.3 +/- 3.11 mM; P <
      0.001), and pH decreased from 6.9 +/- 0.09 to 5.9 +/- 0.04 (P < 0.001).
      Correspondingly, the mRNA expression of NHE1 and NHE3 in the rumen epithelium was
      greater by 20% (P = 0.041) and 25% (P = 0.043) for goats in the CF treatment than
      for those in the PNS treatment. However, in Exp. 2, 16 h of fasting abolished
      differences in ruminal SCFA concentration, pH, and NHE mRNA expression between
      goats in the CF and PNS treatments. In both Exp. 1 and 2, a positive correlation
      was observed between ruminal SCFA concentration and expression of mRNA in NHE1
      and NHE3, whereas expression was negatively correlated with ruminal pH. In in
      vitro studies with isolated rumen epithelial cells from goats fed dried grass,
      exposure to pH of 6.8 or to 20 mM SCFA increased (P < 0.01) NHE1 and NHE3 mRNA
      expression, as compared with exposure to pH of 7.4 or the absence of SCFA. A
      combination of reduced pH (6.8) and SCFA (20 mM) further enhanced (P < 0.05) NHE1
      and NHE3 mRNA expression, indicating synergism between an increased concentration
      of SCFA and low pH (P < 0.05). Messenger RNA expression of NHE2 did not vary in
      vitro with pH (6.8) or SCFA (20 mM) or in vivo in Exp. 1 and 2. Thus, diet
      dependent rumen epithelial NHE1 and NHE3 expression is probably related to
      ruminal SCFA concentration and pH, but that is not the case with NHE2.

PMID- 21856900
TI  - Production traits of litters in 2 crossbred Duroc pig lines.
AB  - Genetics of different pig lines affects litter size, birth weight, and neonatal
      losses. Low birth weight has long been associated with neonatal losses, but
      piglet body mass index is reported to show stronger correlation with stillbirth.
      The aim of this study was to investigate differences in litter size, number of
      stillborn piglets, piglet BW gain, and body mass index between 2 different Duroc
      crossbred lines. Landrace * Yorkshire sows in 2 farms (n = 89) were divided into
      2 groups on each farm. One group of sows on each farm was inseminated with semen
      from Landrace * Duroc boars (boar group LD, n = 48), and the other was
      inseminated with semen from purebred Duroc boars (boar group DD, n = 41). Piglets
      were monitored from birth to weaning at the age of 5 wk. Litter size in boar
      group LD was larger than in boar group DD (P = 0.03). Number of stillborn piglets
      in boar group LD tended to be greater than in boar group DD (P = 0.07). Piglets
      in boar group DD had a greater BW at birth (P = 0.02) and at 3 wk (P = 0.01) than
      those in boar group LD. Body mass index from birth to weaning was greater in
      piglets in boar group DD vs. LD (P < 0.01), and both BW and body mass index of
      liveborn piglets at birth for both groups combined showed a positive correlation
      with survival at weaning (P < 0.01). In conclusion, breeding for larger litter
      size in boar group DD may be one approach to increase the number of vigorous
      piglets in production, but the inverse relationship between litter size and birth
      weight was more pronounced for this group than for boar group LD (P = 0.03).
      Further studies of the impact of litter size on BW gain are necessary before a
      final conclusion can be reached.

PMID- 21856901
TI  - Transcriptome analysis of subcutaneous adipose tissues in beef cattle using 3'
      digital gene expression-tag profiling.
AB  - The molecular mechanisms that regulate fat deposition in bovine adipose tissue
      have not been well studied. To elucidate the genes and gene networks involved in
      bovine fat development, transcriptional profiles of backfat (BF) tissues from
      Hereford * Aberdeen Angus (HEAN, n = 6) and Charolais * Red Angus (CHRA, n = 6)
      steers with high or low BF thickness were characterized by digital gene
      expression-tag profiling. Approximately 9.8 to 21.9 million tags were obtained
      for each library, and a total of 18,034 genes were identified. In total, 650
      genes were found to be differentially expressed, with a greater than 1.5-fold
      difference between the 2 crossbreds (Benjamini-Hochberg false discovery rate <=
      0.05). The majority of differentially expressed genes that were more highly
      expressed in CHRA vs. HEAN were associated with development, whereas the
      differentially expressed genes with greater expression in HEAN vs. CHRA were
      overrepresented in biological processes such as metabolism and immune response.
      Thirty-six and 152 differentially expressed genes were detected between animals
      with high (n = 3) and low (n = 3) BF thickness in HEAN and CHRA, respectively
      (Benjamini-Hochberg false discovery rate <=0.05). The differentially expressed
      genes between high and low groups in CHRA were related to cell proliferation and
      development processes. In addition, lipid metabolism was 1 of the top 5 molecular
      and cellular functions identified in both crossbreds. Ten and 17 differentially
      expressed genes were found to be involved in fat metabolism in HEAN and CHRA,
      respectively. Genes associated with obesity, such as PTX3 (pentraxin 3, long) and
      SERPINE1 (serpin peptidase inhibitor, clade E, member 1), were more highly
      expressed (P < 0.05) in the subset of CHRA animals with greater BF thickness. Our
      study revealed that the expression patterns of genes in BF tissues differed
      depending on the genetic background of the cattle.

PMID- 21856902
TI  - TMEM16A channels generate Ca2+-activated Cl- currents in cerebral artery smooth
      muscle cells.
AB  - Transmembrane protein (TMEM)16A channels are recently discovered membrane
      proteins that display electrophysiological properties similar to classic Ca(2+)
      activated Cl(-) (Cl(Ca)) channels in native cells. The molecular identity of
      proteins that generate Cl(Ca) currents in smooth muscle cells (SMCs) of
      resistance-size arteries is unclear. Similarly, whether cerebral artery SMCs
      generate Cl(Ca) currents is controversial. Here, using molecular biology and
      patch-clamp electrophysiology, we examined TMEM16A channel expression and
      characterized Cl(-) currents in arterial SMCs of resistance-size rat cerebral
      arteries. RT-PCR amplified transcripts for TMEM16A but not TMEM16B-TMEM16H,
      TMEM16J, or TMEM16K family members in isolated pure cerebral artery SMCs. Western
      blot analysis using an antibody that recognized recombinant (r)TMEM16A channels
      detected TMEM16A protein in cerebral artery lysates. Arterial surface
      biotinylation and immunofluorescence indicated that TMEM16A channels are located
      primarily within the arterial SMC plasma membrane. Whole cell Cl(Ca) currents in
      arterial SMCs displayed properties similar to those generated by rTMEM16A
      channels, including Ca(2+) dependence, current-voltage relationship linearization
      by an elevation in intracellular Ca(2+) concentration, a Nerstian shift in
      reversal potential induced by reducing the extracellular Cl(-) concentration, and
      a negative reversal potential shift when substituting extracellular I(-) for Cl(
      ). A pore-targeting TMEM16A antibody similarly inhibited both arterial SMC Cl(Ca)
      and rTMEM16A currents. TMEM16A knockdown using small interfering RNA also
      inhibited arterial SMC Cl(Ca) currents. In summary, these data indicate that
      TMEM16A channels are expressed, insert into the plasma membrane, and generate
      Cl(Ca) currents in cerebral artery SMCs.

PMID- 21856903
TI  - NHE-1 participates in isoproterenol-induced downregulation of SERCA2a and
      development of cardiac remodeling in rat hearts.
AB  - Impaired Ca(2+) handling is one of the main characteristics in heart failure
      patients. Recently, we reported abnormal expressions of Ca(2+)-handling proteins
      in isoproterenol (ISO)-induced hypertrophied rat hearts. On the other hand,
      Na(+)/H(+) exchanger (NHE)-1 inhibitor has been demonstrated to exert beneficial
      effects in ischemic-reperfusion injury and in the development of cardiac
      remodeling. The aims of the present study are to investigate the role of NHE-1 on
      Ca(2+) handling and development of cardiac hypertrophy in ISO-infused rats. Male
      Wistar rats were randomly divided into vehicle [control (CTL)] and ISO groups
      without or with pretreatment with a selective NHE-1 inhibitor, BIIB-723. ISO
      infusion for 1 wk significantly increased the ratios of heart to body weight and
      left ventricle (LV) to body weight and collagen accumulation. All of these
      increases were antagonized by coadministration with BIIB-723. The ISO-induced
      significant increase in LV wall thickness was suppressed significantly (P < 0.05)
      by BIIB-723. ISO-induced decreases in cardiac stroke volume and a total
      mechanical energy per beat index, systolic pressure-volume area at midrange LV
      volume, were normalized by BIIB-723. The markedly higher expression of NHE-1
      protein in the ISO group than that in CTL group was suppressed (P < 0.05) by BIIB
      723. Surprisingly, ISO induced downregulation of the important Ca(2+)-handling
      protein sarcoplasmic reticulum Ca(2+)-ATPase 2a, the expression of which was also
      normalized by BIIB-723 without changes in phosphorylated phospholamban (PLB)/PLB
      expression. We conclude that NHE-1 contributes to ISO-induced abnormal Ca(2+)
      handling associated with cardiac hypertrophy. Inhibition of NHE-1 ameliorates
      cardiac Ca(2+)-handling impairment and prevents the development of cardiac
      dysfunction in ISO-infused rats.

PMID- 21856904
TI  - Onset of atrial arrhythmias elicited by autonomic modulation of rabbit sinoatrial
      node activity: a modeling study.
AB  - Neuronal modulation of the sinoatrial node (SAN) plays a crucial role in the
      initiation and maintenance of atrial arrhythmias (AF), although the exact
      mechanisms remain unclear. We used a computer model of a rabbit right atrium (RA)
      with a heterogeneous SAN and detailed ionic current descriptions for atrial and
      SAN myocytes to explore reentry initiation associated with autonomic activity.
      Heterogeneous acetylcholine (ACh)-dependent ionic responses along with L-type Ca
      current (I(Ca,L)) upregulation were incorporated in the SAN only. During control,
      activation was typical with the leading pacemaker site located close to the
      superior vena cava or the intercaval region. With cholinergic stimulation,
      activation patterns frequently included caudal shifts of the leading pacemaker
      site and occasional double breakouts. The model became increasingly
      arrhythmogenic for the ACh concentration >20 nM and for large I(Ca,L)
      conductance. Reentries obtained included counterclockwise rotors in the free
      wall, clockwise reentry circulating between the SAN and free wall, and typical
      flutter. The SAN was the cause of reentry with a common leading sequence of
      events: a bradycardic beat with shifting in the caudal direction, followed by a
      premature beat or unidirectional block within the SAN. Electrotonic loading, and
      not just overdrive pacing, squelches competing pacemaker sites in the SAN.
      Cholinergic stimulation concomitant with I(Ca,L) upregulation shifts leading
      pacemaker site and can lead to reentry. A heterogeneous response to autonomic
      innervation, a large myocardial load, and an extensive SAN in the intercaval
      region are required for neurally induced SAN-triggered reentry.

PMID- 21856905
TI  - Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after
      pressure overload in insulin resistance.
AB  - Insulin resistance (IR) and systemic hypertension are independently associated
      with heart failure. We reported previously that nitric oxide synthase 3 (NOS3)
      has a beneficial effect on left ventricular (LV) remodeling and function after
      pressure-overload in mice. The aim of our study was to investigate the
      interaction of IR and NOS3 in pressure-overload-induced LV remodeling and
      dysfunction. Wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice were fed either a
      standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet,
      mice underwent transverse aortic constriction (TAC). LV structure and function
      were assessed serially using echocardiography. Cardiomyocytes were isolated, and
      levels of oxidative stress were evaluated using 2',7'-dichlorodihydrofluorescein
      diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and
      ATP production were measured. TAC induced LV remodeling and dysfunction in all
      mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3(-/-)
      mice than in SD-fed WT mice. In contrast, HFD-fed NOS3(-/-) developed less LV
      remodeling and dysfunction and had better survival than did HFD-fed WT mice.
      Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from
      HFD-fed NOS3(-/-) than in those from HFD-fed WT. N(omega)-nitro-L-arginine methyl
      ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone)
      decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice.
      Mitochondrial respiration was altered in NOS3(-/-) mice but did not worsen after
      HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV
      adverse remodeling after pressure overload in HFD-fed, insulin resistant mice.
      Interactions between NOS3 and mitochondria may be responsible for increased
      oxidative stress levels in HFD-fed WT mice hearts.

PMID- 21856906
TI  - Linked opening angle and histological and mechanical aspects of the proximal
      pulmonary arteries of healthy and pulmonary hypertensive rats and calves.
AB  - Understanding how arterial remodeling changes the mechanical behavior of
      pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular
      function. Early and current efforts have focused on the arteries' histological
      changes, their mechanical properties under in vitro mechanical testing, and their
      zero-stress and no-load states. However, the linkage between the histology and
      mechanical behavior is still not well understood. To explore this linkage, we
      investigated the geometry, residual stretch, and histology of proximal PAs in
      both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH),
      compared their changes due to chronic hypoxia across species, and proposed a two
      layer mechanical model of artery to relate the opening angle to the stiffness
      ratio of the PA outer to inner layer. We found that the proximal PA remodeling in
      calves was quite different from that in rats. In rats, the arterial wall
      thickness, inner diameter, and outer layer thickness fraction all increased
      dramatically in PH and the opening angle decreased significantly, whereas in
      calves, only the arterial wall thickness increased in PH. The proposed model
      predicted that the stiffness ratio of the calf proximal PAs changed very little
      from control to hypertensive group, while the decrease of opening angle in rat
      proximal PAs in response to chronic hypoxia was approximately linear to the
      increase of the stiffness ratio. We conclude that the arterial remodeling in rat
      and calf proximal PAs is different and the change of opening angle can be linked
      to the change of the arterial histological structure and mechanics.

PMID- 21856907
TI  - Hypertension from chronic central sodium chloride in mice is mediated by the
      ouabain-binding site on the Na,K-ATPase alpha2-isoform.
AB  - A chronic increase in the concentration of sodium chloride in the cerebrospinal
      fluid (CSF) (?CSF [NaCl]) appears to be critically important for the development
      of salt-dependent hypertension. In agreement with this concept, increasing CSF
      [NaCl] chronically by intracerebroventricular (icv) infusion of NaCl-rich
      artificial CSF (aCSF-HiNaCl) in rats produces hypertension by the same mechanisms
      (i.e., aldosterone-ouabain pathway in the brain) as that produced by dietary
      sodium in salt-sensitive strains. We first demonstrate here that icv aCSF-HiNaCl
      for 10 days also causes hypertension in wild-type (WT) mice. We then used both WT
      and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain
      sensitive Na,K-ATPase alpha(2)-isoform (alpha2(S/S)), mean arterial pressure rose
      by ~25 mmHg within 2 days of starting aCSF-HiNaCl (0.6 nmol Na/min) and remained
      elevated throughout the study. Ouabain (171 pmol/day icv) increased blood
      pressure to a similar extent. aCSF-HiNaCl or ouabain given at the same rates
      subcutaneously instead of intracerebroventricularly had no effect on blood
      pressure. The pressor response to icv aCSF-HiNaCl was abolished by an anti
      ouabain antibody given intracerebroventricularly but not subcutaneously,
      indicating that it is mediated by an endogenous ouabain-like substance in the
      brain. We compared the effects of icv aCSF-HiNaCl or icv ouabain on blood
      pressure in alpha2(S/S) versus knockout/knockin mice with a ouabain-resistant
      endogenous alpha(2)-subunit (alpha2(R/R)). In alpha2(R/R), there was no pressor
      response to icv aCSF-HiNaCl in contrast to WT mice. The alpha2(R/R) genotype also
      lacked a pressor response to icv ouabain. These data demonstrate that chronic
      ?CSF [NaCl] causes hypertension in mice and that the blood pressure response is
      mediated by the ouabain-like substance in the brain, specifically by its binding
      to the alpha(2)-isoform of the Na,K-ATPase.

PMID- 21856908
TI  - Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery.
AB  - The unique contributions of connexin (Cx)37 and Cx40, gap junction-forming
      proteins that are coexpressed in vascular endothelium, to the recovery of tissues
      from ischemic injury are unknown. We recently reported that Cx37-deficient (Cx37(
      /-)) animals recovered ischemic hindlimb function more quickly and to a greater
      extent than wild-type (WT) or Cx40(-/-) animals, suggesting that Cx37 limits
      recovery in the WT animal. Here, we tested the hypothesis that enhanced
      angiogenesis, arteriogenesis, and vasculogenesis contribute to improved
      postischemic hindlimb recovery in Cx37(-/-) animals. Ischemia was induced
      unilaterally in the hindlimbs of WT or Cx37(-/-) mice (isoflurane anesthesia).
      Postsurgical limb appearance, use, and perfusion were documented during recovery,
      and the number (and size) of large and small vessels was determined. Native
      collateral number, predominantly established during embryonic development
      (vasculogenesis), was also determined in the pial circulation. Both microvascular
      density in the gastrocnemius of the ischemic limb (an angiogenic field) and the
      number and tortuosity of larger vessels in the gracilis vasculature (an
      arteriogenic field) were increased in Cx37(-/-) animals compared with WT animals.
      Cx37(-/-) mice also had an increased (vs. WT) number of collateral vessels in the
      pial circulation. These findings suggest that in Cx37(-/-) animals, improved
      recovery of the ischemic hindlimb involves enhanced vasculogenesis, resulting in
      increased numbers of collaterals in the hindlimb (and pial circulations) and more
      extensive collateral remodeling and angiogenesis. These results are consistent
      with Cx37 exerting a growth-suppressive effect in the vasculature that limits
      embryonic vasculogenesis as well as arteriogenic and angiogenic responses to
      ischemic injury in the adult animal.

PMID- 21856909
TI  - Pathophysiology of myocardial reperfusion injury: preconditioning,
      postconditioning, and translational aspects of protective measures.
AB  - Heart diseases due to myocardial ischemia, such as myocardial infarction or
      ischemic heart failure, are major causes of death in developed countries, and
      their number is unfortunately still growing. Preliminary exploration into the
      pathophysiology of ischemia-reperfusion injury, together with the accumulation of
      clinical evidence, led to the discovery of ischemic preconditioning, which has
      been the main hypothesis for over three decades for how ischemia-reperfusion
      injury can be attenuated. The subcellular pathophysiological mechanism of
      ischemia-reperfusion injury and preconditioning-induced cardioprotection is not
      well understood, but extensive research into components, including autacoids, ion
      channels, receptors, subcellular signaling cascades, and mitochondrial
      modulators, as well as strategies for modulating these components, has made
      evolutional progress. Owing to the accumulation of both basic and clinical
      evidence, the idea of ischemic postconditioning with a cardioprotective potential
      has been discovered and established, making it possible to apply this knowledge
      in the clinical setting after ischemia-reperfusion insult. Another a great
      outcome has been the launch of translational studies that apply basic findings
      for manipulating ischemia-reperfusion injury into practical clinical treatments
      against ischemic heart diseases. In this review, we discuss the current findings
      regarding the fundamental pathophysiological mechanisms of ischemia-reperfusion
      injury, the associated protective mechanisms of ischemic pre- and
      postconditioning, and the potential seeds for molecular, pharmacological, or
      mechanical treatments against ischemia-reperfusion injury, as well as subsequent
      adverse outcomes by modulation of subcellular signaling mechanisms (especially
      mitochondrial function). We also review emerging translational clinical trials
      and the subsistent clinical comorbidities that need to be overcome to make these
      trials applicable in clinical medicine.

PMID- 21856910
TI  - Dihydrotestosterone attenuates hypoxia inducible factor-1alpha and cyclooxygenase
      2 in cerebral arteries during hypoxia or hypoxia with glucose deprivation.
AB  - Dihydrotestosterone (DHT) attenuates cytokine-induced cyclooxygenase-2 (COX-2) in
      coronary vascular smooth muscle. Since hypoxia inducible factor-1alpha (HIF
      1alpha) activation can lead to COX-2 production, this study determined the
      influence of DHT on HIF-1alpha and COX-2 following hypoxia or hypoxia with
      glucose deprivation (HGD) in the cerebral vasculature. COX-2 and HIF-1alpha
      levels were assessed via Western blot, and HIF-1alpha activation was indirectly
      measured via a DNA binding assay. Experiments were performed using cerebral
      arteries isolated from castrated male rats treated in vivo with placebo or DHT
      (18 days) followed by hypoxic exposure ex vivo (1% O(2)), cerebral arteries
      isolated from castrated male rats treated ex vivo with vehicle or DHT (10 or 100
      nM; 18 h) and then exposed to hypoxia ex vivo (1% O(2)), or primary human brain
      vascular smooth muscle cells treated with DHT (10 nM; 6 h) or vehicle then
      exposed to hypoxia or HGD. Under normoxic conditions, DHT increased COX-2 (cells
      51%; arteries ex vivo 31%; arteries in vivo 161%) but had no effect on HIF
      1alpha. Following hypoxia or HGD, HIF-1alpha and COX-2 levels were increased;
      this response was blunted by DHT (cells HGD: -47% COX-2, -34% HIF-1alpha; cells
      hypoxia: -29% COX-2, -54% HIF-1alpha; arteries ex vivo: -37% COX-2; arteries in
      vivo: -35% COX-2) and not reversed by androgen receptor blockade. Hypoxia-induced
      HIF-1alpha DNA-binding was also attenuated by DHT (arteries ex vivo and in vivo: 
      55%). These results demonstrate that upregulation of COX-2 and HIF-1alpha in
      response to hypoxia is suppressed by DHT via an androgen receptor-independent
      mechanism.

PMID- 21856911
TI  - MicroRNA-1 transfected embryonic stem cells enhance cardiac myocyte
      differentiation and inhibit apoptosis by modulating the PTEN/Akt pathway in the
      infarcted heart.
AB  - microRNAs (miRs) have emerged as critical modulators of various physiological
      processes including stem cell differentiation. Indeed, miR-1 has been reported to
      play an integral role in the regulation of cardiac muscle progenitor cell
      differentiation. However, whether overexpression of miR-1 in embryonic stem (ES)
      cells (miR-1-ES cells) will enhance cardiac myocyte differentiation following
      transplantation into the infarcted myocardium is unknown. In the present study,
      myocardial infarction (MI) was produced in C57BL/6 mice by left anterior
      descending artery ligation. miR-1-ES cells, ES cells, or culture medium (control)
      was transplanted into the border zone of the infarcted heart, and 2 wk post-MI,
      cardiac myocyte differentiation, adverse ventricular remodeling, and cardiac
      function were assessed. We provide evidence demonstrating enhanced cardiac
      myocyte commitment of transplanted miR-1-ES cells in the mouse infarcted heart as
      compared with ES cells. Assessment of apoptosis revealed that overexpression of
      miR-1 in transplanted ES cells protected host myocardium from MI-induced
      apoptosis through activation of p-AKT and inhibition of caspase-3, phosphatase
      and tensin homolog, and superoxide production. A significant reduction in
      interstitial and vascular fibrosis was quantified in miR-1-ES cell and ES cell
      transplanted groups compared with control MI. However, no statistical
      significance between miR-1-ES cell and ES cell groups was observed. Finally, mice
      receiving miR-1-ES cell transplantation post-MI had significantly improved heart
      function compared with respective controls (P < 0.05). Our data suggest miR-1
      drives cardiac myocyte differentiation from transplanted ES cells and inhibits
      apoptosis post-MI, ultimately giving rise to enhanced cardiac repair,
      regeneration, and function.

PMID- 21856913
TI  - SIRT1-mediated acute cardioprotection.
AB  - Overexpression studies have revealed a role for silent information regulator of
      transcription 1 (SIRT1) lysine deacetylase in cardioprotection against ischemia
      reperfusion injury via long-term transcriptional effects. However, short-term
      SIRT1-mediated lysine deacetylation, within the context of acute
      cardioprotection, is poorly understood. In this study, the role of SIRT1 in the
      acute cardioprotective paradigm of first window ischemic preconditioning (IPC)
      was studied using SIRT1-deficient (SIRT1(+/-)) and SIRT1-overexpressing
      (SIRT1(+++)) mice. In wild-type hearts, cytosolic lysine deacetylation was
      observed during IPC, and overacetylation was observed upon pharmacological SIRT1
      inhibition. Consistent with a role for SIRT1 in IPC, SIRT1(+/-) hearts could not
      be preconditioned and exhibited increased cytosolic lysine acetylation.
      Furthermore, SIRT1(+++) hearts were endogenously protected against ischemia
      reperfusion injury and exhibited decreased cytosolic acetylation. Both of these
      effects in SIRT1(+++) mice were reversed by pharmacological SIRT1 inhibition on
      an acute timescale. Several downstream targets of SIRT1 were examined, with data
      suggesting possible roles for endothelial nitric oxide synthase phosphorylation,
      NF-kappaB, and stimulation of autophagy. In conclusion, these data suggest that
      SIRT1, acting on nontranscriptional targets, is required for cardioprotection by
      acute IPC and that SIRT1-dependent lysine deacetylation occurs during IPC and may
      play a role in cardioprotective signaling.

PMID- 21856912
TI  - A-kinase anchoring proteins: scaffolding proteins in the heart.
AB  - The pleiotropic cyclic nucleotide cAMP is the primary second messenger
      responsible for autonomic regulation of cardiac inotropy, chronotropy, and
      lusitropy. Under conditions of prolonged catecholaminergic stimulation, cAMP also
      contributes to the induction of both cardiac myocyte hypertrophy and apoptosis.
      The formation of localized, multiprotein complexes that contain different
      combinations of cAMP effectors and regulatory enzymes provides the architectural
      infrastructure for the specialization of the cAMP signaling network. Scaffolds
      that bind protein kinase A are called "A-kinase anchoring proteins" (AKAPs). In
      this review, we discuss recent advances in our understanding of how PKA is
      compartmentalized within the cardiac myocyte by AKAPs and how AKAP complexes
      modulate cardiac function in both health and disease.

PMID- 21856914
TI  - Blockade of the TP receptor attenuates the exercise pressor reflex in
      decerebrated rats with chronic femoral artery occlusion.
AB  - Cyclooxygenase metabolites stimulate or sensitize group III and IV muscle
      afferents, which comprise the sensory arm of the exercise pressor reflex. The
      thromboxane (TP) receptor binds several of these metabolites, whose
      concentrations in the muscle interstitium are increased by exercise under freely
      perfused conditions and even more so under ischemic conditions, which occur in
      peripheral artery disease. We showed that the exercise pressor reflex is greater
      in rats with simulated peripheral artery disease than in rats with freely
      perfused limbs. These findings prompted us to test the hypothesis that the TP
      receptor contributes to the exaggerated exercise pressor reflex occurring in a
      rat model of peripheral artery disease. We compared the cardiovascular responses
      to static contraction and stretch before and after femoral arterial injections of
      daltroban (80 MUg), a TP receptor antagonist. We performed these experiments in
      decerebrate rats whose femoral arteries were ligated 72 h before the experiment
      (a model of simulated peripheral artery disease) and in control rats whose
      hindlimbs were freely perfused. Daltroban reduced the pressor response to static
      contraction in both freely perfused (n = 6; before: Delta12 +/- 2 mmHg, after:
      Delta6 +/- 2 mmHg, P = 0.024) and 72-h-ligated rats (n = 10; before: Delta25 +/-
      3 mmHg, after: Delta7 +/- 4 mmHg, P = 0.001). Likewise, daltroban reduced the
      pressor response to stretch in the freely perfused group (n = 9; before: Delta30
      +/- 3 mmHg, after: Delta17 +/- 3 mmHg, P < 0.0001) and in the ligated group (n =
      11; before: Delta37 +/- 5 mmHg, after: Delta23 +/- 3 mmHg, P = 0.016).
      Intravenous injections of daltroban had no effect on the pressor response to
      contraction. We conclude that the TP receptor contributes to the pressor
      responses evoked by contraction and stretch in both freely perfused rats and rats
      with simulated peripheral artery disease.

PMID- 21856915
TI  - Ca2+ sensitization of cardiac myofilament proteins contributes to exercise
      training-enhanced myocardial function in a porcine model of chronic occlusion.
AB  - Exercise training has been shown to improve cardiac dysfunction in both patients
      and animal models of coronary artery disease; however, the underlying cellular
      and molecular mechanisms have not been completely understood. We hypothesized
      that exercise training would improve force generation in the myocardium distal to
      chronic coronary artery occlusion via altered intracellular Ca(2+) concentration
      ([Ca(2+)](i)) cycling and/or Ca(2+) sensitization of myofilaments. Ameroid
      occluders were surgically placed around the proximal left circumflex coronary
      artery of adult female Yucatan pigs. Twenty-two weeks postoperatively, the
      myocardium was isolated from nonoccluded (left anterior descending artery
      dependent) and collateral-dependent (formerly left circumflex coronary artery
      dependent) regions of sedentary (pen confined) and exercise-trained (treadmill
      run, 5 days/wk for 14 wk) pigs. Force measurements in myocardial strips showed
      that the percent change in force at stimulation frequencies of 3 and 4 Hz
      relative to 1 Hz was significantly higher in exercise-trained pigs compared with
      sedentary pigs. beta-Adrenergic stimulation with dobutamine significantly
      improved force kinetics in myocardial strips of sedentary but not exercise
      trained pigs at 1 Hz. Additionally, time to peak and half-decay of intracellular
      Ca(2+) (340-to-380-nm fluoresence ratio) responses at 1 Hz were significantly
      decreased in the collateral-dependent region of exercise-trained pigs with no
      difference in peak [Ca(2+)](i) between groups. Furthermore, the skinned
      myocardium from exercise-trained pigs showed an increase in Ca(2+) sensitivity
      compared with sedentary pigs. Immunoblot analysis revealed that the relative
      levels of cardiac troponin T and beta(1)-adrenergic receptors were decreased in
      hearts from exercise-trained pigs independent of occlusion. Also, the ratio of
      phosphorylated to total myosin light chain-2, basal phosphorylation levels of
      cardiac troponin I (Ser(23) and Ser(24)), and cardiac myosin binding protein-C
      (Ser(282)) were unaltered by occlusion or exercise training. Thus, our data
      demonstrate that exercise training-enhanced force generation in the nonoccluded
      and collateral-dependent myocardium was associated with improved Ca(2+)
      transients, increased Ca(2+) sensitization of myofilament proteins, and decreased
      expression levels of beta(1)-adrenergic receptors and cardiac troponin T.

PMID- 21856916
TI  - Knockout of the Na,K-ATPase alpha2-isoform in the cardiovascular system does not
      alter basal blood pressure but prevents ACTH-induced hypertension.
AB  - The alpha(2)-isoform of Na,K-ATPase (alpha(2)) is thought to play a role in blood
      pressure regulation, but the specific cell type(s) involved have not been
      identified. Therefore, it is important to study the role of the alpha(2) in
      individual cell types in the cardiovascular system. The present study
      demonstrates the role of vascular smooth muscle alpha(2) in the regulation of
      cardiovascular hemodynamics. To accomplish this, we developed a mouse model
      utilizing the Cre/LoxP system to generate a cell type-specific knockout of the
      alpha(2) in vascular smooth muscle cells using the SM22alpha Cre. We achieved a
      90% reduction in the alpha(2)-expression in heart and vascular smooth muscle in
      the knockout mice. Interestingly, tail-cuff blood pressure analysis reveals that
      basal systolic blood pressure is unaffected by the knockout of alpha(2) in the
      knockout mice. However, knockout mice do fail to develop ACTH-induced
      hypertension, as seen in wild-type mice, following 5 days of treatment with ACTH
      (Cortrosyn; wild type = 119.0 +/- 6.8 mmHg; knockout = 103.0 +/- 2.0 mmHg). These
      results demonstrate that alpha(2)-expression in heart and vascular smooth muscle
      is not essential for regulation of basal systolic blood pressure, but alpha(2) is
      critical for blood pressure regulation under chronic stress such as ACTH-induced
      hypertension.

PMID- 21856917
TI  - Short-term oral progesterone administration antagonizes the effect of transdermal
      estradiol on endothelium-dependent vasodilation in young healthy women.
AB  - Very few studies have explored the cardiovascular effects of progesterone in
      premenopausal women. This study aimed to examine the short-term effects of oral
      progesterone alone, transdermal estrogen alone, and progesterone and estrogen
      combined on flow-mediated dilation (FMD) in healthy reproductive-aged women. We
      suppressed endogenous estrogens and progesterone in 17 premenopausal women for 10
      12 days using a gonadotropin-releasing hormone antagonist. On day 4 (hormone
      suppression condition), subjects were tested (n = 17) and were then supplemented
      with either 200 mg micronized progesterone (n = 8) orally or 0.1 mg estradiol (n
      = 9) transdermally per day. On day 7 (progesterone-first or estradiol-first
      condition), subjects were tested and began supplementation with both hormones (n
      = 17) and were tested again on day 10 (combined hormone condition). FMD of the
      brachial artery was assessed using B-mode arterial ultrasound, combined with
      synchronized Doppler analysis. As a result, significant differences in FMD were
      observed between hormone suppression (7.85 +/- 1.06%) and estrogen-first
      conditions (10.14 +/- 1.40%; P < 0.05). The estradiol-induced increase was
      abolished when oral progesterone was also supplemented (6.27 +/- 0.96%). In
      contrast, we observed a trend toward a decrease in FMD with unopposed
      progesterone administration, but no statistically significant differences were
      found between the progesterone-first (6.66 +/- 1.23%), hormone suppression (7.80
      +/- 1.23%), and combined hormone conditions (7.40 +/- 1.29%). In conclusion,
      these data suggest that short-term oral micronized progesterone administration
      antagonizes the beneficial effect of transdermal estradiol on FMD.

PMID- 21856918
TI  - Overexpression of type 1 angiotensin II receptors impairs excitation-contraction
      coupling in the mouse heart.
AB  - Transgenic mice that overexpress human type 1 angiotensin II receptor (AT(1)R) in
      the heart develop cardiac hypertrophy. Previously, we have shown that in 6-mo
      AT(1)R mice, which exhibit significant cardiac remodeling, fractional shortening
      is decreased. However, it is not clear whether altered contractility is
      attributable to AT(1)R overexpression or is secondary to cardiac
      hypertrophy/remodeling. Thus the present study characterized the effects of
      AT(1)R overexpression on ventricular L-type Ca(2+) currents (I(CaL)), cell
      shortening, and Ca(2+) handling in 50-day and 6-mo-old male AT(1)R mice.
      Echocardiography showed there was no evidence of cardiac hypertrophy in 50-day
      AT(1)R mice but that fractional shortening was decreased. Cellular experiments
      showed that cell shortening, I(CaL), and Ca(v)1.2 mRNA expression were
      significantly reduced in 50-day and 6-mo-old AT(1)R mice compared with controls.
      In addition, Ca(2+) transients and caffeine-induced Ca(2+) transients were
      reduced whereas the time to 90% Ca(2+) transient decay was prolonged in both age
      groups of AT(1)R mice. Western blot analysis revealed that sarcoplasmic reticulum
      Ca(2+)-ATPase and Na(+)/Ca(2+) exchanger protein expression was significantly
      decreased in 50-day and 6-mo AT(1)R mice. Overall, the data show that cardiac
      contractility and the mechanisms that underlie excitation-contraction coupling
      are altered in AT(1)R mice. Furthermore, since the alterations in contractility
      occur before the development of cardiac hypertrophy, it is likely that these
      changes are attributable to the increased activity of the renin-angiotensin
      system brought about by AT(1)R overexpression. Thus it is possible that AT(1)R
      blockade may help maintain cardiac contractility in individuals with heart
      disease.

PMID- 21856920
TI  - Alignment of sarcoplasmic reticulum-mitochondrial junctions with mitochondrial
      contact points.
AB  - Propagation of ryanodine receptor (RyR2)-derived Ca(2+) signals to the
      mitochondrial matrix supports oxidative ATP production or facilitates
      mitochondrial apoptosis in cardiac muscle. Ca(2+) transfer likely occurs locally
      at focal associations of the sarcoplasmic reticulum (SR) and mitochondria, which
      are secured by tethers. The outer mitochondrial membrane and inner mitochondrial
      membrane (OMM and IMM, respectively) also form tight focal contacts (contact
      points) that are enriched in voltage-dependent anion channels, the gates of OMM
      for Ca(2+). Contact points could offer the shortest Ca(2+) transfer route to the
      matrix; however, their alignment with the SR-OMM associations remains unclear.
      Here, in rat heart we have studied the distribution of mitochondria-associated SR
      in submitochondrial membrane fractions and evaluated the colocalization of SR-OMM
      associations with contact points using transmission electron microscopy. In a
      sucrose gradient designed for OMM purification, biochemical assays revealed
      lighter fractions enriched in OMM only and heavier fractions containing OMM, IMM,
      and SR markers. Pure OMM fractions were enriched in mitofusin 2, an ~80 kDa
      mitochondrial fusion protein and SR-mitochondrial tether candidate, whereas in
      fractions of OMM + IMM + SR, a lighter (~50 kDa) band detected by antibodies
      raised against the NH(2) terminus of mitofusin 2 was dominating. Transmission
      electron microscopy revealed mandatory presence of contact points at the
      junctional SR-mitochondrial interface versus a random presence along matching SR
      free OMM segments. For each SR-mitochondrial junction at least one tether was
      attached to contact points. These data establish the contact points as anchorage
      sites for the SR-mitochondrial physical coupling. Close coupling of the SR, OMM,
      and IMM is likely to provide a favorable spatial arrangement for local ryanodine
      receptor-mitochondrial Ca(2+) signaling.

PMID- 21856921
TI  - Lower limb-localized vascular phenomena explain initial orthostatic hypotension
      upon standing from squat.
AB  - The cause(s) of initial orthostatic hypotension (transient fall in blood pressure
      within 15 s upon active rising) have not been established. We tested the
      hypothesis that this hypotension is due to local vascular phenomena in
      contracting leg muscles from the brief effort of standing up. Seventeen young
      healthy subjects (2 male and 15 female, 22.5 +/- 1.0 years) performed an active
      rise from resting squat after a 10-s squat, a 1-min squat, or a 5-min squat. Beat
      by-beat arterial blood pressure, cardiac output, heart rate, and stroke volume
      (Finometer finger photoplethysmography) and right common femoral artery blood
      flow (Doppler and Echo ultrasound) were recorded. Data are means +/- SE. Quiet
      standing before squat represented baseline. Peak increases in lower limb and
      total vascular conductance (ml.min(-1).mmHg(-1)) upon standing were not different
      within squat conditions (10-s squat, 50.0 +/- 12.4 vs. 44.3 +/- 5.0; 1-min squat,
      54.7 +/- 9.2 vs. 50.5 +/- 4.5; 5-min squat, 67.4 +/- 13.7 vs. 58.8 +/- 3.9; all P
      > 0.574). Mean arterial blood pressure (in mmHg) fell to a nadir well below
      standing baseline in all conditions despite increases in cardiac output. The
      hypotension predicted by the increase in leg vascular conductance accounted for
      this hypotension [observed vs. predicted (in mmHg): 10-s squat, -17.1 +/- 2.1 vs.
      -18.3 +/- 5.5; 1-min squat, -22.0 +/- 3.8 vs. -25.3 +/- 4.9; 5-min squat, -28.3
      +/- 4.0 vs. -29.2 +/- 6.7]. We conclude that rapid contraction induced dilation
      in leg muscles with the effort of standing, along with a minor potential
      contribution of elevated lower limb arterio-venous pressure gradient, outstrips
      compensatory cardiac output responses and is the cause of initial orthostatic
      hypotension upon standing from squat.

PMID- 21856919
TI  - Reduced NO signaling during pregnancy attenuates outward uterine artery
      remodeling by altering MMP expression and collagen and elastin deposition.
AB  - Recent findings indicate that endothelial nitric oxide (NO) plays a key role in
      uterine artery outward circumferential remodeling during pregnancy. Although the
      underlying mechanisms are not known, they likely involve matrix
      metalloproteinases (MMPs). The goal of this study was to examine the linkage
      among NO inhibition, expansive remodeling, and MMP expression within the uterine
      vascular wall. Adult female rats were treated with N(G)-nitro-L-arginine methyl
      ester [L-NAME (LPLN)] beginning on day 10 of pregnancy and until death at day 20
      and compared with age-matched controls [late pregnant (LP)]. Mean arterial
      pressure of LPLN rats was significantly higher than controls. LPLN fetal and
      placental weights were significantly reduced compared with controls. Main uterine
      arteries (mUA) were collected to determine dimensional properties (lumen area and
      wall thickness), collagen and elastin content, and levels of endothelial nitric
      oxide synthase (eNOS) and MMP expression. Circumferential remodeling was
      attenuated, as evidenced by significantly smaller lumen diameters. eNOS RNA and
      protein were significantly (>90%) decreased in the LPLN mUA compared with LP.
      Collagen and elastin contents were significantly increased in LPLN rats by ~10
      and 25%, respectively, compared with LP (P < 0.05). Both MMP-2 and tissue
      inhibitors of metalloproteinase-2 as assessed by immunofluorescence were lower in
      the endothelium (reduction of 60%) and adventitia (reduction of 50%) of LPLN
      compared with LP mUA. Membrane bound MMP-1 (MT1-MMP) as assessed by immunoblot
      was significantly decreased in LPLN. These data suggest a novel contribution of
      MMPs to gestational uterine vascular remodeling and substantiate the linkage
      between NO signaling and gestational remodeling of the uterine circulation via
      altered MMP, TIMP-2, and MT1-MMP expression and activity.

PMID- 21856923
TI  - Transactivated EGFR mediates alpha1-AR-induced STAT3 activation and cardiac
      hypertrophy.
AB  - alpha(1)-Adrenergic receptor (alpha(1)-AR) is a crucial mediator of cardiac
      hypertrophy. Although numerous intracellular pathways have been implicated in
      alpha(1)-AR-induced hypertrophy, its precise mechanism remains elusive. We aimed
      to determine whether alpha(1)-AR induces cardiac hypertrophy through a novel
      signaling pathway-alpha(1)-AR/epidermal growth factor receptor (EGFR)/signal
      transducer and activator of transcription 3 (STAT3). The activation of STAT3 by
      alpha(1)-AR was first demonstrated by tyrosine phosphorylation, nuclear
      translocation, DNA binding, and transcriptional activity in neonatal Sprague
      Dawley rat cardiomyocytes. Activated STAT3 showed an essential role in alpha(1)
      AR-induced cardiomyocyte hypertrophic growth, as assessed by treatment with STAT3
      inhibitory peptide and lentivirus-STAT3 small interfering RNA. The results were
      further confirmed by in vivo experiments involving intraperitoneal injection of
      the STAT3 inhibitor WP1066 significantly inhibiting phenylephrine-infusion
      induced heart hypertrophy in male C57BL/6 mice. Furthermore, the alpha(1)-AR
      activated STAT3 was associated with transactivation of EGFR because inhibition of
      EGFR with the selective inhibitor AG1478 prevented alpha(1)-AR-induced STAT3
      tyrosine phosphorylation and its transcriptional activity, as well as cardiac
      hypertrophy. In summary, these results suggest that alpha(1)-AR induces the
      activation of STAT3, mainly through transactivation of EGFR, which plays an
      important role in alpha(1)-AR-induced cardiac hypertrophy.

PMID- 21856922
TI  - Maternal hypoxia alters matrix metalloproteinase expression patterns and causes
      cardiac remodeling in fetal and neonatal rats.
AB  - Fetal hypoxia leads to progressive cardiac remodeling in rat offspring. The
      present study tested the hypothesis that maternal hypoxia results in
      reprogramming of matrix metalloproteinase (MMP) expression patterns and fibrillar
      collagen matrix in the developing heart. Pregnant rats were treated with normoxia
      or hypoxia (10.5% O(2)) from day 15 to 21 of gestation. Hearts were isolated from
      21-day fetuses (E21) and postnatal day 7 pups (PD7). Maternal hypoxia caused a
      decrease in the body weight of both E21 and PD7. The heart-to-body weight ratio
      was increased in E21 but not in PD7. Left ventricular myocardium wall thickness
      and cardiomyocyte proliferation were significantly decreased in both fetal and
      neonatal hearts. Hypoxia had no effect on fibrillar collagen content in the fetal
      heart, but significantly increased the collagen content in the neonatal heart.
      Western blotting revealed that maternal hypoxia significantly increased collagen
      I, but not collagen III, levels in the neonatal heart. Maternal hypoxia decreased
      MMP-1 but increased MMP-13 and membrane type (MT)1-MMP in the fetal heart. In the
      neonatal heart, MMP-1 and MMP-13 were significantly increased. Active MMP-2 and
      MMP-9 levels and activities were not altered in either fetal or neonatal hearts.
      Hypoxia significantly increased tissue inhibitors of metalloproteinase (TIMP)-3
      and TIMP-4 in both fetal and neonatal hearts. In contrast, TIMP-1 and TIMP-2 were
      not affected. The results demonstrate that in utero hypoxia reprograms the
      expression patterns of MMPs and TIMPs and causes cardiac tissue remodeling with
      the increased collagen deposition in the developing heart.

PMID- 21856924
TI  - Lactate dilates cochlear capillaries via type V fibrocyte-vessel coupling
      signaled by nNOS.
AB  - Transduction of sound in the inner ear demands tight control over delivery of
      oxygen and glucose. However, the mechanisms underlying the control of regional
      blood flow are not yet fully understood. In this study, we report a novel local
      control mechanism that regulates cochlear blood flow to the stria vascularis, a
      high energy-consuming region of the inner ear. We found that extracellular
      lactate had a vasodilatory effect on the capillaries of the spiral ligament under
      both in vitro and in vivo conditions. The lactate, acting through monocarboxylate
      transporter 1 (MCT1), initiated neuronal nitric oxide (NO) synthase (nNOS) and
      catalyzed production of NO for the vasodilation. Blocking MCT1 with the MCT
      blocker, alpha-cyano-4-hydroxycinnamate (CHC), or a suppressing NO production
      with either the nonspecific inhibitor of NO synthase, N(G)-nitro-L-arginine
      methyl ester (L-NAME), or either of two selective nNOS inhibitors, 3-bromo-7
      nitroindazole or (4S)-N-(4-amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine
      (TFA), totally abolished the lactate-induced vasodilation. Pretreatment with the
      selective endothelial NO synthase inhibitor, L-N(5)-(1-iminoethyl)ornithine (L
      NIO), eliminated the inhibition of lactate-induced vessel dilation. With
      immunohistochemical labeling, we found the expression of MCT1 and nNOS in
      capillary-coupled type V fibrocytes. The data suggest that type V fibrocytes are
      the source of the lactate-induced NO. Cochlear microvessel tone, regulated by
      lactate, is mediated by an NO-signaled coupling of fibrocytes and capillaries.

PMID- 21856925
TI  - RNA interference-mediated survivin gene knockdown induces growth arrest and
      reduced migration of vascular smooth muscle cells.
AB  - Survivin (SVV) is a multifunctional protein that has been implicated in the
      development of neointimal hyperplasia. Nuclear SVV is essential for mitosis,
      whereas in mitochondria SVV has a cytoprotective function. Here, we investigated
      the effects of RNA interference (RNAi)-mediated SVV knockdown on cell cycle
      kinetics, apoptosis, migration, and gene expression in primary cultured vascular
      smooth muscle cells (VSMCs) from the human saphenous vein. Primary Human VSMCs
      were obtained from saphenous veins and cultured under standard conditions. SVV
      knockdown was achieved by either small interfering RNA or lentiviral transduction
      of short hairpin RNA, reducing SVV gene expression by quantitative PCR (>75%, P <
      0.01) without a loss of cell viability. Subcellular fractionation revealed that
      RNAi treatment effectively targeted the nuclear SVV pool, whereas the larger
      mitochondrial pool was much less sensitive to transient knockdown. Both p53 and
      p27 protein levels were notably increased. SVV RNAi treatment significantly
      blocked VSMC proliferation in response to serum and PDGF-AB, arresting VSMC
      growth. Cell cycle analysis revealed an increased G(2)/M fraction consistent with
      a mitotic defect; 4',6-diamidino-2-phenylindole staining confirmed an increased
      frequency of polyploid and abnormal nuclei. In a transwell assay, SVV knockdown
      reduced migration to PDGF-AB, and actin-phalloidin staining revealed disorganized
      actin filaments and polygonal cell shape. However, apoptosis (DNA content and
      annexin V flow cytometry) was not directly induced by SVV RNAi, and sensitivity
      to apoptotic agonists (e.g., staurosporine and cytokines) was unchanged. In
      conclusion, RNAi-mediated SVV knockdown in VSMCs leads to profound cell cycle
      arrest at G(2)/M and impaired chemotaxis without cytotoxicity. The regulation of
      mitosis and apoptosis in VSMC involves differentially regulated subcellular pools
      of SVV. Thus, treatment of VSMC with RNAi targeting SVV might limit the response
      to vascular injury without destabilizing the vessel wall.

PMID- 21856926
TI  - Mechanisms underlying altered extracellular nucleotide-induced contractions in
      mesenteric arteries from rats in later-stage type 2 diabetes: effect of ANG II
      type 1 receptor antagonism.
AB  - Little is known about the vascular contractile responsiveness to, and signaling
      pathways for, extracellular nucleotides in the chronic stage of type 2 diabetes
      or whether the ANG II type 1 receptor blocker losartan might alter such
      responses. We hypothesized that nucleotide-induced arterial contractions are
      augmented in diabetic Goto-Kakizaki (GK) rats and that treatment with losartan
      would normalize the contractions. Here, we investigated the vasoconstrictor
      effects of ATP/UTP in superior mesenteric arteries isolated from GK rats (37-42
      wk old) that had or had not received 2 wk of losartan (25 mg.kg(-1).day(-1)). In
      arteries from GK rats (vs. those from Wistar rats), 1) ATP- and UTP-induced
      contractions, which were blocked by the nonselective P2 antagonist suramin, were
      enhanced, and these enhancements were suppressed by endothelial denudation, by
      cyclooxygenase (COX) inhibitors, or by a cytosolic phospholipase A(2) (cPLA(2))
      inhibitor; 2) both nucleotides induced increased release of PGE(2) and
      PGF(2alpha); 3) nucleotide-stimulated cPLA(2) phosphorylations were increased; 4)
      COX-1 and COX-2 expressions were increased; and 5) neither P2Y2 nor P2Y6 receptor
      expression differed, but P2Y4 receptor expression was decreased. Mesenteric
      arteries from GK rats treated with losartan exhibited (vs. untreated GK) 1)
      reduced nucleotide-induced contractions, 2) suppressed UTP-induced release of
      PGE(2) and PGF(2alpha), 3) suppressed UTP-stimulated cPLA(2) phosphorylation, 4)
      normalized expressions of COX-2 and P2Y4 receptors, and 5) reduced superoxide
      generation. Our data suggest that the diabetes-related enhancement of ATP
      mediated vasoconstriction was due to P2Y receptor-mediated activation of the
      cPLA(2)/COX pathway and, moreover, that losartan normalizes such contractions by
      a suppressing action within this pathway.

PMID- 21856927
TI  - Complications of bioabsorbable suture anchors in the shoulder.
AB  - The development of the suture anchor has played a pivotal role in the transition
      from open to arthroscopic techniques of the shoulder. Various suture anchors have
      been manufactured that help facilitate the ability to create a soft tissue to
      bone repair. Because of reported complications of loosening, migration, and
      chondral injury with metallic anchors, bioabsorbable anchors have become
      increasingly used among orthopaedic surgeons. In this review, the authors sought
      to evaluate complications associated with bioabsorbable anchors in or about the
      shoulder and understand these in the context of the total number of bioabsorbable
      anchors placed. In 2008, 10 bioabsorbable anchor-related complications were
      reported to the US Food and Drug Administration. The reported literature
      complications of bioabsorbable anchors implanted about the shoulder include
      glenoid osteolysis, synovitis, and chondrolysis. These potential complications
      should be kept in mind when forming a differential diagnosis in a patient in whom
      a bioabsorbable anchor has been previously used. These literature reports, which
      amount to but a fraction of the total bioabsorbable anchors implanted in the
      shoulder on a yearly basis, underscore the relative safety and successful
      clinical results with use of bioabsorbable suture anchors. Product development
      continues with newer composites such as PEEK (polyetheretherketone) and calcium
      ceramics (tricalcium phosphate) in an effort to hypothetically create a
      mechanically stable construct with and improve biocompatibility of the implant.
      Bioabsorbable anchors remain a safe, reproducible, and consistent implant to
      secure soft tissue to bone in and about the shoulder. Meticulous insertion
      technique must be followed in using bioabsorbable anchors and may obviate many of
      the reported complications found in the literature. The purpose of this review is
      to provide an overview of the existing literature as it relates to the rare
      complications seen with use of bioabsorbable suture anchors in the shoulder.

PMID- 21856928
TI  - Prevalence of septic arthritis after anterior cruciate ligament reconstruction
      among professional athletes.
AB  - BACKGROUND: Septic arthritis of the knee after anterior cruciate ligament (ACL)
      reconstruction is a rare complication. Its prevalence and characteristics have
      never been reported among professional athletes. PURPOSE: To report the
      prevalence and the characteristics of septic arthritis after ACL reconstruction
      in professional athletes and a general population of patients. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: A retrospective analysis of a
      consecutive series of 1957 patients who underwent an ACL reconstruction between
      2003 and 2008 was performed; 88 patients were professional athletes. The patient
      demographics, the prevalence of infection, the involved organism, and the method
      of treatment were reviewed. Three potential risk factors for infection-level of
      sporting participation, indoor/outdoor sports, and the presence or not of a
      combined lateral tenodesis-were assessed using univariate and multivariate
      logistic regression analysis. RESULTS: The prevalence of septic arthritis was
      0.37% in the nonprofessional group and 5.7% in the professional athlete
      population. Being a professional athlete (odds ratio [OR], 16.0; 95% confidence
      interval [CI], 3.9-59.8; P = .0001) or having a combined lateral tenodesis (OR,
      4.8; 95% CI, 1.04-18.04; P = .02) was found to be significantly correlated with
      septic arthritis after ACL reconstruction. A significant correlation exists
      between being a professional athlete and having a combined lateral tenodesis
      (chi(2) = 16.7; P = 4 * 10(-5)), suggesting a potential confounding role is
      played by one of these variables. All the cases of infection in the professional
      athletes occurred in those who participated in outdoor sports, although this was
      not found to be statistically significant (P = .17). CONCLUSION: Participation in
      professional sports and having a combined lateral tenodesis are risk factors for
      the development of infection after ACL reconstruction. We hypothesize that
      professional athletes may be part of a specific group of patients at higher risk
      of infection after ACL reconstruction.

PMID- 21856929
TI  - Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic
      chondrocytes.
AB  - BACKGROUND: Platelet-rich plasma (PRP) has recently been postulated as a
      treatment for osteoarthritis (OA). Although anabolic effects of PRP on
      chondrocytes are well documented, no reports are known addressing effects on
      cartilage degeneration. Since OA is characterized by a catabolic and inflammatory
      joint environment, the authors investigated whether PRP was able to counteract
      the effects of such an environment on human osteoarthritic chondrocytes.
      HYPOTHESIS: Platelet-rich plasma inhibits inflammatory effects of interleukin-1
      (IL-1) beta on human osteoarthritic chondrocytes. STUDY DESIGN: Controlled
      laboratory study. METHODS: Human osteoarthritic chondrocytes were cultured in the
      presence of IL-1 beta to mimic an osteoarthritic environment. Medium was
      supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of
      PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1),
      aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs
      (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin
      endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG)
      content, nitric oxide (NO) production, and nuclear factor kappa B (NFkappaB)
      activation were studied. RESULTS: Platelet-rich plasma releasate diminished IL-1
      beta-induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced
      IL-1 beta-induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene
      expression and GAG content were not influenced by IL-1 beta or additional PRPr.
      Matrix metalloproteinase 13 gene expression and NO production were upregulated by
      IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta-induced
      NFkappaB activation to control levels containing no IL-1 beta. CONCLUSION:
      Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta
      mediated effects on human osteoarthritic chondrocytes, including inhibition of
      NFkappaB activation. CLINICAL RELEVANCE: Platelet-rich plasma releasate
      counteracts effects of an inflammatory environment on genes regulating matrix
      degradation and formation in human chondrocytes. Platelet-rich plasma releasate
      decreases NFkappaB activation, a major pathway involved in the pathogenesis of
      OA. These results encourage further study of PRP as a treatment for OA.

PMID- 21856930
TI  - Traumatic spinal cord injuries in horseback riding: a 35-year review.
AB  - BACKGROUND: Spinal cord injury (SCI) is a potentially disabling neurologic injury
      that can occur in horseback riding. To date, no published study has examined the
      epidemiology of SCI from horseback riding in the United States, and few
      international studies exist on this topic. Several studies have described
      traumatic brain injuries, spine fractures, and extremity injuries; however, SCI
      patterns and outcomes in horseback riders are poorly understood. PURPOSE: This
      study was undertaken to characterize the demographics, SCI patterns, and
      neurologic outcomes of persons with SCIs related to horseback riding. STUDY
      DESIGN: Descriptive epidemiologic study. METHODS: This is a retrospective review
      of 121 SCI cases from horseback riding in the National SCI Statistical Center
      database from 1973 to 2008. The treatment setting was 26 U.S. SCI Model Systems
      of Care. The number of injuries, gender, age, and SCI type for horseback riding
      were compared with other sports and activities. The level of preserved neurologic
      function, SCI completeness, American Spinal Injury Association classification,
      and mechanical ventilation use at discharge were examined in the horseback riding
      group. RESULTS: The mean age of injury was 37.8 years (standard deviation, 15.2).
      The majority of patients were white (88%) and female (50.4%). Compared with
      diving, motorcycle riding, football, and gymnastics, horseback riding involved a
      significantly higher number of women (P < .005), a higher mean age of injury, and
      an equal likelihood of resulting in paraplegia and tetraplegia. The most common
      levels of preserved neurologic function were C4-C6, T12, and L1. Spinal cord
      injury from horseback riding most commonly resulted in incomplete tetraplegia
      (41%) followed by complete paraplegia (24%). Only 4 patients required mechanical
      ventilation on discharge from acute inpatient rehabilitation. CONCLUSION: Spinal
      cord injury from horseback riding affects an equal proportion of women and men,
      has a wide age range, and most commonly results in incomplete tetraplegia
      followed by complete paraplegia. Study findings improve awareness of the
      demographics and neurologic outcomes of individuals with SCI from horseback
      riding and can help guide future studies evaluating SCI mechanisms in horseback
      riders to improve injury prevention and management.

PMID- 21856931
TI  - Ncb2 is involved in activated transcription of CDR1 in azole-resistant clinical
      isolates of Candida albicans.
AB  - We recently demonstrated that CDR1 overexpression in azole-resistant isolates of
      Candida albicans is due to its enhanced transcriptional activation and increased
      mRNA stability. In this study, we provide the first evidence of transcriptional
      regulation of CDR1 by Ncb2, the beta subunit of NC2, a heterodimeric regulator of
      transcription. Conditional NCB2 null mutants displayed decreased susceptibility
      toward azole and an enhanced transcription of CDR1. Interestingly, Ncb2
      associated with the CDR1 promoter under both repression and activation; however,
      an increase in recruitment was observed under both transient and constitutive
      activation states. By chromatin immunoprecipitation (ChIP) assay, we showed the
      preferential recruitment of Ncb2 to the core TATA region under activation (azole
      resistant isolate), while under repression (azole-susceptible isolate) it was
      present at the TATA upstream region. Further, ChIP analysis revealed that Ncb2
      binding was not restricted to the CDR1 gene; instead, it was observed on the
      promoters of genes coregulated with CDR1 by the transcription activator Tac1. The
      tac1Delta null mutants, which fail to show the drug-induced transient activation
      of CDR1, also showed no increase in Ncb2 recruitment at the promoter. Taken
      together, our results show that Ncb2, in conjunction with Tac1, is involved in
      the transcriptional activation of CDR1, opening up new therapeutic possibilities
      to combat multidrug resistance (MDR) in C. albicans.

PMID- 21856932
TI  - Cellular effects and epistasis among three determinants of adaptation in
      experimental populations of Saccharomyces cerevisiae.
AB  - Epistatic interactions in which the phenotypic effect of an allele is conditional
      on its genetic background have been shown to play a central part in various
      evolutionary processes. In a previous study (J. B. Anderson et al., Curr. Biol.
      20:1383-1388, 2010; J. R. Dettman, C. Sirjusingh, L. M. Kohn, and J. B. Anderson,
      Nature 447:585-588, 2007), beginning with a common ancestor, we identified three
      determinants of fitness as mutant alleles (each designated with the letter "e")
      that arose in replicate Saccharomyces cerevisiae populations propagated in two
      different environments, a low-glucose and a high-salt environment. In a low
      glucose environment, MDS3e and MKT1e interacted positively to confer a fitness
      advantage. Also, PMA1e from a high-salt environment interacted negatively with
      MKT1e in a low-glucose environment, an example of a Dobzhansky-Muller
      incompatibility that confers reproductive isolation. Here we showed that the
      negative interaction between PMA1e and MKT1e is mediated by alterations in
      intracellular pH, while the positive interaction between MDS3e and MKT1e is
      mediated by changes in gene expression affecting glucose transporter genes. We
      specifically addressed the evolutionary significance of the positive interaction
      by showing that the presence of the MDS3 mutation is a necessary condition for
      the spread and fixation of the new mutations at the identical site in MKT1. The
      expected mutations in MKT1 rose to high frequencies in two of three experimental
      populations carrying MDS3e but not in any of three populations carrying the
      ancestral allele. These data show how positive and negative epistasis can
      contribute to adaptation and reproductive isolation.

PMID- 21856933
TI  - T cell-derived Act1 is necessary for IL-25-mediated Th2 responses and allergic
      airway inflammation.
AB  - The cellular and molecular mechanisms driven by IL-25 and its cognate receptor IL
      17RB necessary for the promotion of Th2-mediating pathogenic pulmonary
      inflammation remains to be defined. We have previously reported the critical role
      of the U-box-type E3 ubiquitin ligase Act1 (1) for the downstream signaling of
      the IL-17 cytokine family including the Th2-promoting cytokine IL-25 (IL-17E)
      (2). In this study, we report that IL-25-driven but not conventional IL-4-driven
      Th2 polarization and cytokine production is impaired in Act1-deficient T cells.
      Also, Act1 deficiency in the T cell compartment results in the abrogation of
      eosinophilic airway infiltration as well as airway hyperresponsiveness in mouse
      models of Ag-induced airway inflammation. The in vivo generation of Ag-specific
      Th2 cytokine-producing cells is defective in the absence of Act1 expression in T
      cells after OVA/aluminum hydroxide immunization. Notably, the production of OVA
      specific IgG(1) but not IgG(2a) or IgE is also impaired. At the molecular level,
      we report that IL-25-mediated induction of Th2 master regulator GATA-3 and the
      transcription factor GFI-1 is attenuated in Act1-deficient T cells. Taken
      together, our findings indicate that Act1 expression in T cells is required for
      cellular and humoral Th2-mediated allergic responses and the development of
      airway hyperresponsiveness, in part, through Act1's function in IL-25-induced
      development of Th2 T cells.

PMID- 21856934
TI  - Decreased AIRE expression and global thymic hypofunction in Down syndrome.
AB  - The Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy,
      higher propensity to organ-specific autoimmune disorders, and higher
      susceptibility to infections, among other features. Considering that AIRE
      (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene
      expression in surgically removed thymuses from 14 DS patients with congenital
      heart defects, who were compared with 42 age-matched controls with heart anomaly
      as an isolated malformation. Immunohistochemistry revealed 70.48 +/- 49.59 AIRE
      positive cells/mm(2) in DS versus 154.70 +/- 61.16 AIRE-positive cells/mm(2) in
      controls (p < 0.0001), and quantitative PCR as well as DNA microarray data
      confirmed those results. The number of FOXP3-positive cells/mm(2) was equivalent
      in both groups. Thymus transcriptome analysis showed 407 genes significantly
      hypoexpressed in DS, most of which were related, according to network
      transcriptional analysis (FunNet), to cell division and to immunity. Immune
      response-related genes included those involved in 1) Ag processing and
      presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell
      differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A,
      CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1,
      and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time
      PCR analyses. These findings on global thymic hypofunction in DS revealed
      molecular mechanisms underlying DS immune phenotype and strongly suggest that DS
      immune abnormalities are present since early development, rather than being a
      consequence of precocious aging, as widely hypothesized. Thus, DS should be
      considered as a non-monogenic primary immunodeficiency.

PMID- 21856936
TI  - Simvastatin inhibits IFN regulatory factor 4 expression and Th17 cell
      differentiation in CD4+ T cells derived from patients with multiple sclerosis.
AB  - Subsequent to the clinical trial of simvastatin in patients with relapsing
      remitting multiple sclerosis (RR MS), which demonstrated the ability of
      simvastatin to inhibit new inflammatory CNS lesion formation, the current in
      vitro study has characterized the mechanisms through which simvastatin inhibits
      Th17 cell differentiation. The anti-inflammatory effects of statins are mediated
      by the inhibition of isoprenylation, which ensures proper membrane insertion and
      function of proteins. Small GTPases, involved in multiple signal transduction
      pathways, are the key targets for isoprenylation. We report that simvastatin, one
      of the most hydrophobic statins with good CNS penetration, inhibited Th17 cell
      differentiation and IL-17A, IL-17F, IL-21, and IL-22 secretion in in vitro
      differentiated naive CD4(+) T cells from RR MS patients. Simvastatin exerted a
      less prominent effect on the cells from healthy controls, as it inhibited only IL
      17F secretion. The inhibition of Th17 cell differentiation was mediated via
      inhibition of IFN regulatory factor 4 (IRF4) expression, which was identified as
      a key transcription factor for human Th17 cell differentiation using both IRF4
      gene knockdown and overexpression experiments. In studies addressing which
      isoprenylation pathway--geranylgeranylation or farnesylation--is inhibited by
      simvastatin, we demonstrated that the geranylgeranyl transferase inhibitor
      replicated the effect of simvastatin. Selective inhibition of geranylgeranylated
      RhoA-associated kinase replicated the effect of simvastatin on the inhibition of
      IRF4 expression and IL-17A, IL-17F, IL-21, and IL-22 secretion, presenting a
      promising new therapeutic approach for this disabling disease.

PMID- 21856935
TI  - Antioxidant c-FLIP inhibits Fas ligand-induced NF-kappaB activation in a
      phosphatidylinositol 3-kinase/Akt-dependent manner.
AB  - Fas ligand (FasL) belongs to the TNF family of death ligands, and its binding to
      the FasR leads to activation of several downstream signaling pathways and
      proteins, including NF-kappaB and PI3K/Akt. However, it is not known whether
      cross-talk exists between NF-kappaB and PI3K/Akt in the context of FasL
      signaling. We demonstrate using both human renal epithelial 293T cells and Jurkat
      T-lymphocyte cells that although FasL activates both Akt and NF-kappaB, Akt
      inhibits FasL-dependent NF-kappaB activity in a reactive oxygen species-dependent
      manner. Cellular FLICE-inhibitory protein (c-FLIP), an antioxidant and an
      important component of the death-inducing signaling complex, also represses NF
      kappaB upstream of the regulatory IkappaB kinase-gamma protein subunit in the NF
      kappaB signaling pathway, and positive cross-talk exists between Akt and c-FLIP
      in the context of inhibition of FasL-induced NF-kappaB activity. The presence of
      two death effector domains of c-FLIP and S-nitrosylation of its caspase-like
      domain were found to be important for mediating c-FLIP-dependent downregulation
      of NF-kappaB activity. Taken together, our study reveals a novel link between NF
      kappaB and PI3K/Akt and establishes c-FLIP as an important regulator of FasL
      mediated cell death.

PMID- 21856937
TI  - Structural basis for Fc gammaRIIa recognition of human IgG and formation of
      inflammatory signaling complexes.
AB  - The interaction of Abs with their specific FcRs is of primary importance in host
      immune effector systems involved in infection and inflammation, and are the
      target for immune evasion by pathogens. FcgammaRIIa is a unique and the most
      widespread activating FcR in humans that through avid binding of immune complexes
      potently triggers inflammation. Polymorphisms of FcgammaRIIa (high responder/low
      responder [HR/LR]) are linked to susceptibility to infections, autoimmune
      diseases, and the efficacy of therapeutic Abs. In this article, we define the
      three-dimensional structure of the complex between the HR (arginine, R134) allele
      of FcgammaRIIa (FcgammaRIIa-HR) and the Fc region of a humanized IgG1 Ab,
      hu3S193. The structure suggests how the HR/LR polymorphism may influence
      FcgammaRIIa interactions with different IgG subclasses and glycoforms. In
      addition, mutagenesis defined the basis of the epitopes detected by FcR blocking
      mAbs specific for FcgammaRIIa (IV.3), FcgammaRIIb (X63-21), and a pan FcgammaRII
      Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with
      residues defined by crystallography to contact IgG. Finally, crystal structures
      of LR (histidine, H134) allele of FcgammaRIIa and FcgammaRIIa-HR reveal two
      distinct receptor dimers that may represent quaternary states on the cell
      surface. A model is presented whereby a dimer of FcgammaRIIa-HR binds Ag-Ab
      complexes in an arrangement that possibly occurs on the cell membrane as part of
      a larger signaling assembly.

PMID- 21856938
TI  - G alpha i2 and ZAP-70 mediate RasGRP1 membrane localization and activation of SDF
      1-induced T cell functions.
AB  - RasGRP1, a Ras guanine-nucleotide exchange factor, critically mediates T cell
      development and function and controls immunodeficiency and autoimmunity. In this
      study, we describe a unique mechanism of mobilization and activation of RasGRP1
      in response to SDF-1, a chemokine that signals via the G protein-coupled receptor
      CXCR4. Depletion of RasGRP1 impaired SDF-1-stimulated human T cell migration,
      expression of the activation marker CD69, and activation of the ERK MAPK pathway,
      indicating that RasGRP1 mediates SDF-1 functions. SDF-1 treatment caused RasGRP1
      to localize to the plasma membrane to activate K-Ras and to the Golgi to activate
      N-Ras. These events were required for cellular migration and for ERK activation
      that mediates downstream transcriptional events in response to SDF-1. SDF-1
      dependent localization of RasGRP1 did not require its diacylglycerol-binding
      domain, even though diacyglycerol was previously shown to mediate localization of
      RasGRP1 in response to Ag stimulation. This domain was, however, required for
      activity of RasGRP1 after its localization. Intriguingly, SDF-1 treatment of T
      cells induced the formation of a novel molecular signaling complex containing
      RasGRP1, Galphai2, and ZAP-70. Moreover, SDF-1-mediated signaling by both Gi
      proteins and ZAP-70 was required for RasGRP1 mobilization. In addition, RasGRP1
      mobilization and activation in response to SDF-1 was dependent on TCR expression,
      suggesting that CXCR4 heterodimerizes with the TCR to couple to ZAP-70 and
      mobilize RasGRP1. These results increase understanding of the molecular
      mechanisms that mediate SDF-1 effects on T cells and reveal a novel mechanism of
      RasGRP1 regulation. Other G protein-coupled receptors may similarly contribute to
      regulation of RasGRP1.

PMID- 21856941
TI  - Comment on "Endothelial ICAM-1 protein induction is regulated by cytosolic
      phospholipase A2alpha via both NF-kappaB and CREB transcription factors".

PMID- 21856939
TI  - HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in
      APCs leads to programmed death-1 ligand upregulation and suppression of HIV
      specific CD8 T cells.
AB  - Recent evidence demonstrates that HIV-1 infection leads to the attenuation of
      cellular immune responses, which has been correlated with the increased
      expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is
      induced upon T cell activation, and its prolonged expression facilitates CD8(+) T
      cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2,
      which are expressed on APCs. Importantly, early reports demonstrated that
      blockade of the PD-1/PD-L interaction by Abs may help to counter the development
      of immune exhaustion driven by HIV viral persistence. To better understand the
      regulation of the PD-1 pathway during HIV infection, we examined the ability of
      the virus to induce PD-L expression on macrophages and dendritic cells. We found
      a direct relationship between the infection of APCs and the expression of PD-L1
      in which virus-mediated upregulation induced a state of nonresponsiveness in
      uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was
      revitalized by the blockade of PD-L1, after which T cells regained their capacity
      for proliferation and the secretion of proinflammatory cytokines IFN-gamma, IL-2,
      and IL-12 upon restimulation. In addition, we identify a critical role for the
      PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by
      HIV, because inhibition of these intracellular signal transducer enzymes
      significantly reduced PD-L1 induction by infection. These data identify a novel
      mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a
      new role for virus-infected cells in the local corruption of immune responses
      required for viral suppression.

PMID- 21856942
TI  - Which lymphoid cells express MHC class II antigens; are TCRs encoded within the
      MHC?

PMID- 21856943
TI  - A mouse B-cell alloantigen determined by gene(s) linked to the major
      histocompatibility complex. The Journal of Experimental Medicine. 1973. 138: 1289
      1304.

PMID- 21856946
TI  - Dynamics of the plague-wildlife-human system in Central Asia are controlled by
      two epidemiological thresholds.
AB  - Plague (caused by the bacterium Yersinia pestis) is a zoonotic reemerging
      infectious disease with reservoirs in rodent populations worldwide. Using one
      half of a century of unique data (1949-1995) from Kazakhstan on plague dynamics,
      including data on the main rodent host reservoir (great gerbil), main vector
      (flea), human cases, and external (climate) conditions, we analyze the full
      ecoepidemiological (bubonic) plague system. We show that two epidemiological
      threshold quantities play key roles: one threshold relating to the dynamics in
      the host reservoir, and the second threshold relating to the spillover of the
      plague bacteria into the human population.

PMID- 21856944
TI  - CD4+FOXP3+ T regulatory cells in human autoimmunity: more than a numbers game.
AB  - Regulatory T cells (Treg) play a dominant role in suppression of autoimmune
      pathology, as rescue of Treg number and/or function in model systems can both
      prevent and reverse disease. These findings have generated a series of studies
      addressing the role of defects in Treg number and function in human autoimmunity.
      However, demonstrating global defects in Treg of individuals diagnosed with
      autoimmune diseases has been challenging. These challenges are founded, in part,
      in the complexity of human autoimmune diseases in which various genetic factors
      and environmental triggers contribute to disease susceptibility. Moreover,
      contribution of failed Treg-mediated suppression to pathogenesis can extend to
      multiple mechanisms. In this article, we discuss what is known with respect to
      the number and function of CD4(+)FOXP3(+) Treg in human autoimmunity, focusing on
      representative autoimmunediseases in which there are diverse Treg-mediated
      defects. We also highlight the need to better understand Treg plasticity and
      function in the context of autoimmunity.

PMID- 21856948
TI  - Showdown at the RXLR motif: Serious differences of opinion in how effector
      proteins from filamentous eukaryotic pathogens enter plant cells.

PMID- 21856949
TI  - Functional melanocytes derived from human pluripotent stem cells engraft into
      pluristratified epidermis.
AB  - Melanocytes are essential for skin homeostasis and protection, and their defects
      in humans lead to a wide array of diseases that are potentially extremely severe.
      To date, the analysis of molecular mechanisms and the function of human
      melanocytes have been limited because of the difficulties in accessing large
      numbers of cells with the specific phenotypes. This issue can now be addressed
      via a differentiation protocol that allows melanocytes to be obtained from
      pluripotent stem cell lines, either induced or of embryonic origin, based on the
      use of moderate concentrations of a single cytokine, bone morphogenic protein 4.
      Human melanocytes derived from pluripotent stem cells exhibit all the
      characteristic features of their adult counterparts. This includes the enzymatic
      machinery required for the production and functional delivery of melanin to
      keratinocytes. Melanocytes also integrate appropriately into organotypic
      epidermis reconstructed in vitro. The availability of human cells committed to
      the melanocytic lineage in vitro will enable the investigation of those
      mechanisms that guide the developmental processes and will facilitate analysis of
      the molecular mechanisms responsible for genetic diseases. Access to an unlimited
      resource may also prove a vital tool for the treatment of hypopigmentation
      disorders when donors with matching haplotypes become available in clinically
      relevant banks of pluripotent stem cell lines.

PMID- 21856950
TI  - NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite
      associated arthropathy.
AB  - The proinflammatory and catabolic cytokine IL-1beta has been implicated in the
      pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and
      cartilage degeneration. Although synovial macrophages are suggested to be the
      source of IL-1beta, the mechanism remains unclear. Ectopic deposition of
      hydroxyapatite (HA) crystals in joints is closely associated with OA and other
      arthropathies, but the precise role of HA in arthritis pathogenesis has not been
      clearly demonstrated. Here we show that HA crystals of a particular size and
      shape can stimulate robust secretion of proinflammatory cytokines IL-1beta and IL
      18 from murine macrophages in a NLRP3 inflammasome-dependent manner. HA-induced
      inflammasome activation is dependent on potassium efflux, generation of reactive
      oxygen species (ROS), and lysosomal damage, but independent of cell death. Mice
      lacking the inflammasome components are protected against HA-induced neutrophilic
      inflammation in the air-pouch model of synovitis, and they show decreased joint
      pathology accompanying spontaneous HA deposition in the ank-deficient mouse model
      of arthritis. Moreover, calcium crystal positive synovial fluids from some OA
      patients exhibited inflammasome-stimulatory activity in vitro. These results
      demonstrate that the NLRP3 inflammasome mediates the pathological effect of HA
      crystals in vitro and in vivo and suggest a critical role for the inflammasome in
      the pathogenesis of OA.

PMID- 21856951
TI  - Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for
      binding to transmembrane protein Frizzled4.
AB  - The Wnt signaling pathway is essential for the development of diverse tissues
      during embryogenesis. Signal transduction is activated by the binding of Wnt
      proteins to the type I receptor low-density lipoprotein receptor-related protein
      5/6 and the seven-pass transmembrane protein Frizzled (Fzd), which contains a Wnt
      binding site in the form of a cysteine-rich domain. Known extracellular
      antagonists of the Wnt signaling pathway can be subdivided into two broad classes
      depending on whether they bind primarily to Wnt or to low-density lipoprotein
      receptor-related protein 5/6. We show that the secreted protein Tsukushi (TSK)
      functions as a Wnt signaling inhibitor by binding directly to the cysteine-rich
      domain of Fzd4 with an affinity of 2.3 * 10(-10) M and competing with Wnt2b. In
      the developing chick eye, TSK is expressed in the ciliary/iris epithelium,
      whereas Wnt2b is expressed in the adjacent anterior rim of the optic vesicle,
      where it controls the differentiation of peripheral eye structures, such as the
      ciliary body and iris. TSK overexpression effectively antagonizes Wnt2b signaling
      in chicken embryonic retinal cells both in vivo and in vitro and represses Wnt
      dependent specification of peripheral eye fates. Conversely, targeted
      inactivation of the TSK gene in mice causes expansion of the ciliary body and up
      regulation of Wnt2b and Fzd4 expression in the developing peripheral eye. Thus,
      we uncover a crucial role for TSK as a Wnt signaling inhibitor that regulates
      peripheral eye formation.

PMID- 21856952
TI  - Nucleotide oligomerization domain-containing proteins instruct T cell helper type
      2 immunity through stromal activation.
AB  - Although a number of studies have examined the development of T-helper cell type
      2 (Th2) immunity in different settings, the mechanisms underlying the initiation
      of this arm of adaptive immunity are not well understood. We exploited the fact
      that immunization with antigen plus either nucleotide-binding oligomerization
      domain-containing proteins 1 (Nod1) or 2 (Nod2) agonists drives Th2 induction to
      understand how these pattern-recognition receptors mediate the development of
      systemic Th2 immune responses. Here, we show in bone-marrow chimeric mice that
      Nod1 and Nod2 expression within the stromal compartment is necessary for priming
      of effector CD4(+) Th2 responses and specific IgG1 antibodies. In contrast,
      sensing of these ligands by dendritic cells was not sufficient to induce Th2
      immunity, although these cells contribute to the response. Moreover, we
      determined that CD11c(+) cells were the critical antigen-presenting cells,
      whereas basophils and B cells did not affect the capacity of Nod ligands to
      induce CD4(+) Th2 effector function. Finally, we found that full Th2 induction
      upon Nod1 and Nod2 activation was dependent on both thymic stromal lymphopoietin
      production by the stromal cells and the up-regulation of the costimulatory
      molecule, OX40 ligand, on dendritic cells. This study provides in vivo evidence
      of how systemic Th2 immunity is induced in the context of Nod stimulation. Such
      understanding will influence the rational design of therapeutics that could
      reprogram the immune system during an active Th1-mediated disease, such as
      Crohn's disease.

PMID- 21856953
TI  - A mechanism emerges for the critical period hypothesis for estrogen treatment.

PMID- 21856954
TI  - Multidimensional assessment of homework: an analysis of students with ADHD.
AB  - OBJECTIVE: Homework can have beneficial effects for students; however, it
      presents challenges, particularly for students with attention problems. Although
      effective homework interventions exist, intervention development and evaluation
      has been hampered by the lack of psychometrically sound measures. The primary
      purpose of this study was to evaluate the construct validity of the Homework
      Performance Questionnaire (HPQ), Parent and Teacher Versions, in a sample of
      children with ADHD. A secondary purpose was to examine variations in homework
      performance as a function of individual characteristics, such as academic
      achievement, quality of the family-school relationship, and child's diagnostic
      status. METHOD: The sample included 91 children (34% female) with ADHD in Grades
      2 to 6. Measures included parent and teacher ratings of homework performance and
      the quality of the parent-teacher relationship as well as direct assessment of
      child academic achievement and homework performance (i.e., samples of completed
      assignments). Correlational analyses were used to examine construct validity, and
      ANOVAs were used to evaluate group differences. RESULTS: Each factor of the HPQ
      had a significant relationship with other measures of relevant constructs. There
      were no significant differences in homework performance between groups for ADHD
      subtype, medication status, or comorbidity, with the exception of learning
      disability. Children with ADHD and learning disabilities had significantly lower
      teacher ratings of academic competence. CONCLUSION: Results of the present study
      suggest that HPQ scores may be used to make valid inferences about the homework
      performance of children with attention problems. These rating scales may be
      helpful in progress monitoring and evaluating intervention effectiveness.

PMID- 21856955
TI  - Effectiveness of a therapeutic summer camp for children with ADHD: Phase I
      Clinical Intervention Trial.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness of a 2
      week therapeutic summer day camp for children with ADHD, which included a social
      skills training program and parent psychoeducation and training program. This was
      an open-label, nonrandomized Phase I Clinical Intervention Trial. METHOD: Parents
      completed the Weiss Functional Impairment Rating Scale (WFIRS) and the Conners'
      Global Index-Parent Version (CGI-P), and children completed the Index of Peer
      Relations (IPR). All questionnaires were completed prior to the camp and 3 weeks
      after starting school. A total of 33 children who attended the camp were compared
      with a group of 15 children with ADHD who did not attend camp. RESULTS: CGI-P,
      IPR, and WFIRS significantly improved in the group that attended the camp but not
      in the control group. Effect sizes were between 0.7 and 1.6. CONCLUSION: The
      therapeutic summer day camp is effective in improving ADHD symptoms, peer
      relationships, and overall functioning of children.

PMID- 21856956
TI  - The business case for quality: economic analysis of the Michigan Keystone Patient
      Safety Program in ICUs.
AB  - Health care-associated infections affect an estimated 5% of hospitalized patients
      and represent one of the leading causes of illness and death in the United
      States. This study calculates the costs and benefits of a patient safety program
      in intensive care units in 6 hospitals that were part of the Michigan Keystone
      ICU Patient Safety Program. On average, 29.9 catheter-related bloodstream
      infections and 18.0 cases of ventilator-associated pneumonia were averted per
      hospital on an annual basis. The average cost of the intervention is $3375 per
      infection averted, measured in 2007 dollars. The cost of the intervention is
      substantially less than estimates of the additional health care costs associated
      with these infections, which range from $12 208 to $56 167 per infection episode.
      These results do not take into account the additional effect of the Michigan
      Keystone program in terms of reducing cases of sepsis or its effects in terms of
      preventing mortality, improving teamwork, and reducing nurse turnover.

PMID- 21856957
TI  - Establishing a culture of blood management through education: a quality
      initiative study of postoperative blood use in CABG patients at Methodist DeBakey
      Heart & Vascular Center.
AB  - Blood management strategies are crucial in light of transfusion-related health
      risks to patients and the relative scarcity and cost of blood products. The
      authors describe a collaborative quality initiative to reduce blood use in their
      coronary artery bypass graft (CABG) population and other cardiovascular intensive
      care unit (CVICU) patients. A multidisciplinary team was engaged at all levels of
      patient care. The 2-part initiative involved a direct educational component
      emphasizing transfusion risk awareness and patient-centered blood management
      strategies accompanied by a data-based component that included monthly
      dissemination of blood product use to the relevant service lines. The authors
      observed a reduction in postoperative blood product use among CABG patients
      (14.3% decrease in the first year; 30.6% from 2006 to 2008) and an 18.2%
      reduction in blood product volume used in the entire CVICU, with no additional
      harm to patients and a trend toward better outcomes. This team-driven paradigm
      change has made blood management everyone's initiative.

PMID- 21856958
TI  - The quality improvement marathon: slow pace for overall improvement while access
      remains far behind.

PMID- 21856960
TI  - Declaring.

PMID- 21856961
TI  - Patient-centred communication: a sophisticated procedure.

PMID- 21856962
TI  - Autosomal recessive cerebellar ataxias: the current state of affairs.
AB  - Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs)
      encompass a diverse group of rare neurodegenerative disorders in which a
      cerebellar syndrome is the key clinical feature. The clinical overlap between the
      different cerebellar ataxias, the occasional atypical phenotypes, and the genetic
      heterogeneity often complicate the clinical management of such patients. Despite
      the steady increase in newly discovered ARCA genes, many patients with a putative
      ARCA cannot be genotyped yet, proving that more genes must be involved. This
      review presents an updated overview of the various ARCAs. The clinical and
      genetic characteristics of those forms with a known molecular genetic defect are
      discussed, along with the emerging insights in the underlying pathophysiological
      mechanisms.

PMID- 21856963
TI  - Barriers to care for children and youth with special health care needs:
      perceptions of Illinois pediatricians.
AB  - OBJECTIVE. To assess primary care pediatricians' (PCPs') perceptions of caring
      for children and youth with special health care needs (CYSHCN). METHODS. Cross
      sectional survey of Illinois pediatricians. RESULTS. Thirty-five percent of
      surveys were returned and 26% were analyzed. The top 3 perceived barriers were
      insufficient time (72%), insufficient reimbursement (68%), and lack of support
      services (59%). Insufficient interest was the least cited barrier (19%).
      Preparedness to perform tasks related to care of CYSHCN ranged from 89% for
      accessing early intervention services to 24% for billing and coding. The
      percentage of PCPs somewhat or very comfortable providing primary care to
      patients with technology dependence ranged from 75% for blood glucose monitoring
      to 12% for dialysis. CONCLUSIONS. The issues of time, reimbursement, billing, and
      coding are perceived as significant barriers to the care CYSHCN. There is
      substantial variation in PCPs' comfort in the care of CYSHCN who require the
      assistance of medical technologies.

PMID- 21856964
TI  - Parent-reported reasons for nonreceipt of recommended adolescent vaccinations,
      national immunization survey: teen, 2009.
AB  - OBJECTIVES: To identify parent-reported reasons for non-receipt of adolescent
      vaccinations by provider recommendation status. METHODS: Parental reasons for non
      receipt of adolescent vaccines were analyzed among adolescents 13-17 years using
      data from the 2009 National Immunization Survey-Teen (n=20,066). RESULTS: Among
      unvaccinated adolescents, 87.9% (Td/Tdap), 90.9% (MenACWY), and 66.0% (HPV) of
      parents reported that they did not receive a healthcare provider recommendation
      for their adolescent to receive the vaccine. Among those without a provider
      recommendation, the most common reasons for not receiving the vaccines were
      'vaccine not recommended' [Td/Tdap, MenACWY] and 'not needed' [HPV]. Among those
      with a recommendation, the most common parental reasons were 'lack of knowledge'
      [Td/Tdap], 'vaccine not needed' [MenACWY], and 'lack of knowledge' [HPV].
      CONCLUSIONS: Non-receipt of provider recommendations was a main parent-reported
      reason for not getting vaccinated. Increasing parental knowledge and vaccination
      coverage through increased provider-parent communication about disease risk and
      vaccine benefits is needed.

PMID- 21856965
TI  - Postdischarge feeding patterns in early- and late-preterm infants.
AB  - OBJECTIVE: To compare the incidence of postdischarge feeding dysfunction and
      hospital/subspecialty visits for feeding problems during the first year of life
      in late (34 to 36 6/7 weeks) and early-preterm (25 to 33 6/7 weeks) infants.
      METHODS: In this prospective study, the authors sent questionnaires to parents of
      early (n = 319) and late (n = 571) preterm infants at 3, 6, and 12 months
      corrected age. Parents' perceptions of infants' feeding skills, comfort with
      feeding, and hospital/subspecialty visits for feeding difficulties were obtained.
      Results were analyzed with chi(2) tests and Spearman's correlations. RESULTS:
      Early preterms had more oromotor dysfunction at 3 (29% vs 17%) and 12 months (7%
      vs 4%) and more avoidant feeding behavior at 3 months (33% vs 29%). In both
      groups, oromotor dysfunction and avoidant feeding behavior improved over time.
      Frequency of poor appetite and hospitalization/subspecialty visits were similar.
      CONCLUSION: Pediatricians should screen all preterm infants for feeding
      dysfunction during the first year.

PMID- 21856966
TI  - Metabolomics reveals elevated macromolecular degradation in periodontal disease.
AB  - Periodontitis is a chronic inflammatory disease characterized by tissue
      destruction. In the diseased oral environment, saliva has primarily been
      considered to act as a protectant by lubricating the tissue, mineralizing the
      bones, neutralizing the pH, and combating microbes. To understand the metabolic
      role that saliva plays in the diseased state, we performed untargeted metabolomic
      profiling of saliva from healthy and periodontitic individuals. Several classes
      of biochemicals, including dipeptide, amino acid, carbohydrate, lipids, and
      nucleotide metabolites, were altered, consistent with increased macromolecular
      degradation of proteins, triacylglycerol, glycerolphospholipids, polysaccharides,
      and polynucleotides in the individuals with periodontal disease. These changes
      partially reflected the enhanced host-bacterial interactions in the diseased
      state as supported by increased levels of bacterially modified amino acids and
      creatine metabolite. More importantly, the increased lipase, protease, and
      glycosidase activities associated with periodontitis generated a more favorable
      energy environment for oral bacteria, potentially exacerbating the disease state.

PMID- 21856967
TI  - Assessment of phonation threshold pressure: a critical review and clinical
      implications.
AB  - PURPOSE: To describe the origins of the task elicitation procedure for
      determining phonation threshold pressure and, through a literature review and
      online survey, describe published procedural, environmental, and participant
      variable departures from the original methodology. METHOD: Literature search
      terms included phonation threshold pressure, subglottal pressure and phonation,
      pressure measurement and phonation, lung pressure and phonation, and vocal fold
      oscillation onset. Inclusion criteria were limited to indirect assessment of
      phonation threshold pressure, English language publications between 1980 and
      2009, and peer-reviewed journals. Studies including animals, computer or physical
      models, alaryngeal speakers, laryngeal airway resistance, or any airflow
      interruption technique were excluded. Twenty-four articles matched the
      inclusionary criteria. An online survey to query task elicitation procedures was
      then developed from the literature review. RESULTS: The scientific rationale for
      inclusion of phonation threshold pressure data was consistent across published
      studies; however, variations in procedural methodology for task elicitation were
      identified, as were environmental and participant inconsistencies that might
      affect phonation threshold pressure values. Findings of the online survey
      mirrored the inconsistencies identified in the literature review. CONCLUSIONS:
      The methodological differences for task elicitation identified in this
      comprehensive review of the literature and the online survey, while bringing into
      question the reliability of phonation threshold pressure measurement, illuminate
      scientific questions yet to be answered to further refine and potentially
      standardize phonation threshold pressure as a more reliable research and clinical
      measurement.

PMID- 21856968
TI  - The impact of teacher responsivity education on preschoolers' language and
      literacy skills.
AB  - PURPOSE: This study examined the extent to which teacher responsivity education
      affected preschoolers' language and literacy development over an academic year.
      Additional aims were to determine whether children's initial language abilities
      and teachers' use of responsivity strategies were associated with language
      outcomes, in particular. METHOD: In this randomized controlled trial, preschool
      centers were assigned to a responsivity education intervention (n = 19 centers,
      25 teachers, and 174 children) or a "business-as-usual" control condition (n = 19
      centers, 24 teachers, and 156 children). Teachers within the intervention centers
      received training focused on a set of strategies designed to promote children's
      engagement and participation in extended conversational interactions across the
      school day. RESULTS: Hierarchical linear models showed no main effects on
      children's language skills, although moderating effects were observed such that
      the intervention appeared to have positive effects for children with relatively
      high initial language abilities. In addition, teacher use of responsivity
      strategies was positively associated with vocabulary development. With regard to
      children's literacy skills, there was a significant main effect of the
      intervention on print-concept knowledge. CONCLUSIONS: Although teacher
      responsivity education is viewed as benefitting children's language and literacy
      development, the impacts of this type of intervention on children's skills
      warrant further investigation.

PMID- 21856969
TI  - Cerebral metabolism, cognition, and functional abilities in Alzheimer disease.
AB  - Patients with Alzheimer disease (AD) exhibit profound difficulties in completing
      instrumental activities of daily living (IADLs), such as managing finances,
      organizing medications, and food preparation. It is unclear which brain areas
      underlie IADL deficits in AD. To address this question, we used voxel-based
      analysis to correlate the performance of IADLs with resting cerebral metabolism
      as measured during [(18)F] fluorodeoxyglucose-positron emission tomography (FDG
      PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was
      associated with hypometabolism in right-sided cortical regions, including the
      parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and
      frontal pole. Follow-up path analyses examining anatomically defined regions of
      interest (ROI) demonstrated that the association between metabolism and IADLs was
      mediated by global cognition in frontal ROIs, and partially mediated by global
      cognition in the parietal ROI. Findings suggest that hypometabolism of right
      sided brain regions involved in executive functioning, visuospatial processing,
      attention, and working memory underlie functional impairments in patients with
      AD.

PMID- 21856970
TI  - Anemia associated with depressive symptoms in mild cognitive impairment with
      severe white matter hyperintensities.
AB  - Depression with mild cognitive impairment (MCI) may be associated with a high
      risk of dementia. Likewise, anemia and subcortical ischemic changes might be
      associated with depression in the elderly individuals. We examined the
      relationship between anemia, subcortical ischemic changes, and depressive
      symptoms in 388 elderly patients with MCI (74.0% women, mean age = 71.8) who were
      evaluated at the Clinical Research Center for Dementia of South Korea. Blood
      samples were drawn from all consenting participants and depressive symptoms were
      assessed using the 15-item Geriatric Depression Scale (GDS-15). We also evaluated
      the severity of white matter hyperintensities (WMH) on brain using magnetic
      resonance imaging (MRI). After a multivariable adjustment, we found no
      significant differences in GDS-15 score between anemic and nonanemic groups (F =
      3.0, P = .085) and among WMH level groups (F = 0.6, P = .574) independently.
      However, the interaction between anemia and the severity of WMH was significantly
      associated with depressive symptoms (analysis of covariance, F = 7.8, P < .001).
      In post hoc tests, a higher depressive symptom score was observed in anemic
      participants with severe WMH. Anemia with severe subcortical ischemic changes
      appears to be related to depressive symptoms in patients with MCI.

PMID- 21856971
TI  - The IQCODE versus a single-item informant measure to discriminate between
      cognitively intact individuals and individuals with dementia or cognitive
      impairment.
AB  - The present study evaluated the short Informant Questionnaire on Cognitive
      Decline in the Elderly (IQCODE 2-year version) against a single item concerning
      informant's perception of patient's memory, as screening tools for CIND not
      dementia (CIND) and dementia. Data were drawn from the Aging, Demographics, and
      Memory Study, which is a national study that was specifically designed to provide
      population-based estimates of cognitive impairment and dementia in the United
      States. The study employed a comprehensive dementia evaluation that yielded an
      expert consensus-based diagnosis. Receiver-operating curves, sensitivity,
      specificity, negative predictive value, and positive predictive value were
      calculated. Both the IQCODE and the single-item instrument demonstrated only mild
      to-moderate abilities to discriminate between cognitively intact individuals and
      individuals with CIND. Whereas the ability of the IQCODE to discriminate between
      cognitively intact individuals and individuals with dementia was moderate, the
      single-item instrument showed an adequate ability to distinguish between
      cognitively intact individuals and individuals with dementia. Therefore, for
      screening purposes, asking informants a single question concerning patients'
      memory is sufficient. However, if additional data concerning patients' strengths
      and weaknesses are needed, the IQCODE may be desirable.

PMID- 21856972
TI  - Characteristics of peripheral arterial disease and its relevance to the diabetic
      population.
AB  - Peripheral arterial disease (PAD) is very frequent in diabetics, and it increases
      with age. Foot examination contributes poorly to diagnosis of PAD. The ankle
      brachial index (ABI) measurement is considered the most accurate noninvasive
      diagnostic method when evaluating PAD: ABI evaluation is recommended in all
      diabetics aged >50 years. Many diabetic patients with PAD have a concomitant
      sensitive neuropathy: as a consequence, perception of ischemic pain is remarkably
      reduced or completely blocked. The result is that the prevalence of claudication
      in the diabetic population with PAD is lower than the prevalence of critical limb
      ischemia (CLI) in this population. CLI is a major risk factor for lower extremity
      amputation without revascularization. Ankle and toe pressures and oxygen tension
      at the foot are the noninvasive diagnostic parameters of CLI though the medial
      artery calcification inhibits accurate determination of the ankle and toe
      pressures, especially when a forefoot ulcer is present. In diabetics, the
      anatomical localization is mainly distal; arterial wall calcification is
      frequently observed and occlusion occurs more frequently than stenosis. Such
      anatomical features, along with the difficulties in the diagnostic approach,
      account for the fundamental role of CLI as the main prognostic indicator for
      major amputation. PAD is an expression of systemic atherosclerotic disease.
      Prognosis of patients with PAD is related to the presence and extent of
      underlying coronary artery disease (CAD) but also to the severity of PAD: in
      particular, patients in whom revascularization is not feasible have the highest
      mortality rate.

PMID- 21856973
TI  - Differential keratin expression during epiboly in a wound model of bioengineered
      skin and in human chronic wounds.
AB  - Epiboly represents the process by which keratinocytes migrate to envelop a
      surface. The authors have been investigating a living bilayered skin construct
      (BSC) that is used in the treatment of lower extremity wounds due to venous
      insufficiency and diabetes. The construct demonstrates epiboly after injury and
      incubation in vitro, and this model may be useful for studying epidermal
      migration and the process of skin maturation. Punch biopsies of the construct in
      vitro were cultured and immunostained for specific keratins at baseline and at 24
      to 72 hours. For comparison, skin biopsy specimens from human chronic venous
      ulcers and acute healing wounds were similarly processed. The authors found that
      K1 and K10 were fully expressed in the epidermis of the fully epibolized surface
      on BSC. K1 was also present in the migrating edge of specimens, whereas K10 was
      not detectable. K16 and K6 were evident in normal skin and the epibolized area of
      the construct; K6 expression was very prominent in the migrating edge.
      Importantly, K17 was distinctly limited to the epibolized surface and the
      migrating edge, and its expression was very similar to that observed in healing
      human wounds. In conclusion, differential expression of keratins in this epiboly
      model closely reflects in vivo studies and supports keratin specificity in the
      processes of migration and differentiation of new epidermis. Therefore, these
      findings provide further and important validity for the study of
      epithelialization and the hope of developing prognostic markers for venous ulcer
      healing.

PMID- 21856974
TI  - Factors affecting gentamicin penetration in lower extremity ischemic tissues with
      ulcers.
AB  - The aims of the study were to analyze the penetration of gentamicin in foot
      ulcers in patients with different severities of peripheral arterial disease (PAD)
      and to determine significant parameters affecting lower limb tissue
      concentrations. Patients undergoing debridement of a wound or an amputation
      procedure were included. All patients received a 120 mg or 240 mg intravenous
      dose of gentamicin prior to the procedure. Patients were classified according to
      the degree of PAD. Tissue and serum samples were collected at the time of
      intervention, and gentamicin concentrations were determined by fluorescence
      polarization immunoassay. Blood and tissue samples were taken from 61 patients,
      41 males and 20 females with a mean age of 66 years. Nineteen patients had nil or
      borderline PAD, 9 patients had mild or moderate PAD, and 26 patients had severe
      PAD. Forty-eight patients had type 2 diabetes, 8 patients had type 1 diabetes,
      and 5 patients were nondiabetic. The concentration of gentamicin in peripheral
      skeletal muscle tissue was dependent on the serum concentration, degree of PAD,
      gender, and age. For patients with ischemic lower extremity wounds (patients with
      mild, moderate, and severe PAD), the concentration of gentamicin was
      significantly lower (P = .010) than the concentration in nonischemic wounds, and
      the concentration in female patients was also significantly lower than in male
      patients (P = .047). The concentration in peripheral subcutaneous tissue was
      0.663 times the concentration in skeletal muscle tissue (P < .00001). Gentamicin
      showed greatest penetration in male patients without PAD. For patients with
      severe PAD, higher doses of gentamicin may be required to achieve the same
      effect.

PMID- 21856975
TI  - Principles and technique of foam sclerotherapy and its specific use in the
      treatment of venous leg ulcers.
AB  - Invention of foam sclerotherapy has significantly changed the current
      phlebological practice. Compared with liquid sclerosants, obliterating foam is
      more efficient, especially for the closure of larger veins. This review discusses
      clinical aspects of foam sclerotherapy with a focus on its use for the treatment
      of venous leg ulceration, including the rationale for its use in the treatment of
      these chronic wounds, physicochemical mechanisms responsible for stability and
      disintegration of sclerosant foam, pathomechanism of neurologic adverse events
      seen after foam sclerotherapy, and techniques that can increase efficacy of this
      procedure and lower frequency of adverse events.

PMID- 21856976
TI  - Leuconostoc mesenteroides subsp. suionicum subsp. nov.
AB  - Strains LMG 8159 and LMG 11499 were reclassified by a polyphasic approach,
      including 16S rRNA gene sequence analysis, 16S-23S rRNA intergenic spacer (IGS)
      sequence analysis, (GTG)(5)-PCR fingerprinting, RAPD fingerprinting, fatty acid
      methyl ester analysis and an analysis of phenotypic features using API 50 CH. The
      two strains were closely related to the type strains of the three defined
      subspecies of Leuconostoc mesenteroides, showing 99.7-99.9% 16S rRNA gene
      sequence similarity, 99.2% 16S-23S rRNA gene intergenic spacer sequence
      similarity, 97.1-97.4% pheS gene sequence similarity and 98.0-98.2% rpoA gene
      sequence similarity. Low atpA gene sequence similarity (91.4-91.7%), (GTG)(5)-PCR
      fingerprinting, RAPD fingerprinting, fatty acid compositions and phenotypic
      features allowed us to differentiate strains LMG 8159 and LMG 11499 from all
      established subspecies within L. mesenteroides. Based upon the data obtained in
      the present and previous studies, a novel subspecies is proposed within the
      species L. mesenteroides, Leuconostoc mesenteroides subsp. suionicum subsp. nov.,
      with the type strain LMG 8159(T) (=ATCC 9135(T) =DSM 20241(T) =NCIMB 6992(T)).

PMID- 21856977
TI  - Idiomarina aquimaris sp. nov., isolated from the reef-building coral Isopora
      palifera.
AB  - A bacterial strain designated SW15(T) was isolated from a sample of the reef
      building coral Isopora palifera, collected in southern Taiwan. The novel strain
      was characterized using a polyphasic taxonomic approach. Cells of strain SW15(T)
      were Gram-negative, aerobic, light yellow, rod-shaped and motile by means of a
      single polar flagellum. In phylogenetic analyses based on 16S rRNA gene
      sequences, strain SW15(T) appeared to belong to the genus Idiomarina in the class
      Gammaproteobacteria and to be most closely related to Idiomarina homiensis PO
      M2(T) (97.6% sequence similarity). Strain SW15(T) exhibited optimal growth
      between 20 and 30  degrees C, with NaCl between 3% and 4% (w/v) and at a pH value
      between 7 and 8. Predominant cellular fatty acids were iso-C(15:0) (31.1%), iso
      C(17:0) (15.4%), iso-C(17:1)omega9c (10.0%) and C(16:0) (8.8%). The major
      respiratory quinone was ubiquinone Q-8. The polar lipid profile consisted of a
      mixture of phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylserine, an uncharacterized aminolipid and
      several uncharacterized phospholipids. The DNA G+C content was 51.1 mol%. The
      level of DNA-DNA relatedness between strain SW15(T) and Idiomarina homiensis PO
      M2(T) was 42.6-56.5%. The results of physiological and biochemical tests allowed
      the clear phenotypic differentiation of the novel strain from established species
      of the genus Idiomarina. Based on the genotypic, phenotypic and chemotaxonomic
      data, strain SW15(T) represents a novel species in the genus Idiomarina, for
      which the name Idiomarina aquimaris sp. nov. is proposed, with SW15(T) (=LMG
      25374(T)=BCRC 80083(T)) as the type strain.

PMID- 21856978
TI  - Salinibacter iranicus sp. nov. and Salinibacter luteus sp. nov., isolated from a
      salt lake, and emended descriptions of the genus Salinibacter and of Salinibacter
      ruber.
AB  - Two Gram-staining-negative, red- and orange-pigmented, non-motile, rod-shaped,
      extremely halophilic bacteria, designated strains CB7(T) and DGO(T), were
      isolated from Aran-Bidgol salt lake, Iran. Growth occurred at NaCl concentrations
      of between 2 and 5 M NaCl and the isolates grew optimally with 3 M NaCl. The
      optimum pH and temperature for growth of the two strains were pH 7.5 and 37 
      degrees C, and they were able to grow over pH and temperature ranges of pH 6-8
      and 25-50  degrees C. The predominant fatty acids of the two isolates were
      C(18:1)omega7c, iso-C(15:0) and summed feature 3 (C(16:1)omega7c and/or iso
      C(15:0) 2-OH). The polar lipid pattern of the two isolates consisted of
      diphosphatidylglycerol, phosphatidylcholine, three unidentified lipids, one
      unidentified aminolipid and three unidentified glycolipids. The only quinone
      present was menaquinone 7 (MK-7). The G+C contents of the genomic DNA of strains
      CB7(T) and DGO(T) were 64.8 and 65.6 mol%, respectively. 16S rRNA gene sequence
      analysis indicated that strains CB7(T) and DGO(T) were related to Salinibacter
      ruber in the phylum Bacteroidetes. Levels of 16S rRNA gene sequence similarity
      between strains CB7(T) and DGO(T) and Salinibacter ruber DSM 13855(T) were 93.2
      and 93.6%, respectively. The two novel strains shared 98.9% 16S rRNA gene
      sequence similarity. DNA-DNA hybridization experiments between strains CB7(T) and
      DGO(T) and Salinibacter ruber DSM 13855(T) indicated levels of relatedness of 44
      and 52%, respectively, while the level of relatedness between the two new
      isolates was 53%. Chemotaxonomic data supported the placement of strains CB7(T)
      and DGO(T) in the genus Salinibacter. DNA-DNA hybridization studies and
      biochemical and physiological characterization allowed strains CB7(T) and DGO(T)
      to be differentiated from Salinibacter ruber and from each other. They are
      therefore considered to represent two novel species of the genus Salinibacter,
      for which the names Salinibacter iranicus sp. nov. (type strain CB7(T)=IBRC-M
      10036(T)=CGMCC 1.11003(T)) and Salinibacter luteus sp. nov. (type strain
      DGO(T)=IBRC-M 10423(T)=CGMCC 1.11002(T)) are proposed. Emended descriptions of
      the genus Salinibacter and of Salinibacter ruber are also presented.

PMID- 21856979
TI  - Sphingomonas alpina sp. nov., a psychrophilic bacterium isolated from alpine
      soil.
AB  - An aerobic, Gram-negative-staining, motile, psychrophilic bacterium, designated
      strain S8-3(T), was isolated from alpine soil. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that strain S8-3(T) was related to the genus
      Sphingomonas and had highest 16S rRNA gene sequence similarity with Sphingomonas
      oligophenolica S213(T) (98.0%). 16S RNA gene sequence similarity between strain
      S8-3(T) and Sphingomonas paucimobilis ATCC 29837(T) (the type species of the
      genus Sphingomonas) was 93.0%. Strain S8-3(T) contained Q-10 as the ubiquinone
      and C(18:1)omega7c (65.0%) and C(14:0) 2-OH (13.4%) as the dominant fatty acids
      (>10%). The major polyamines were the triamine sym-homospermidine and spermidine.
      The polar lipid profile contained sphingoglycolipid, phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylmonomethylethanolamine. The DNA G+C content was 64.1 mol%. Combined
      data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated
      that strain S8-3(T) is a representative of a novel species of the genus
      Sphingomonas, for which the name Sphingomonas alpina sp. nov. is proposed. The
      type strain is S8-3(T) (=DSM 22537(T)=LMG 26055(T)).

PMID- 21856980
TI  - Postechiella marina gen. nov., sp. nov., isolated from seawater.
AB  - A Gram-staining-negative, strictly aerobic, non-motile, yellow-pigmented
      bacterium, designated strain M091(T), was isolated from seawater at Damupo beach
      in Pohang, Republic of Korea, and investigated using a polyphasic taxonomic
      approach. The novel strain grew optimally at 25  degrees C, pH 7.0-8.0, and in
      the presence of 3% (w/v) NaCl. In a phylogenetic analysis based on 16S rRNA gene
      sequences, strain M091(T) formed a lineage within the family Flavobacteriaceae
      that was distinct from the most closely related genera of Flaviramulus (95.1%
      sequence similarity), Algibacter (94.9-93.9%), Mariniflexile (94.8-94.2%),
      Winogradskyella (94.8-93.2%), Lacinutrix (94.7-93.8%) and Tamlana (94.7-92.9%).
      The polar lipid profile of the novel strain comprised phosphatidylethanolamine,
      two unidentified aminolipids, one unidentified phospholipid and seven
      unidentified lipids. The predominant cellular fatty acids were iso-C(15:0)
      (20.5%), iso-C(17:0) 3-OH (15.4%), iso-C(15:0) 3-OH (12.4%), C(15:0) (10.9%) and
      iso-C(15:1) G (9.9%). The genomic DNA G+C content of strain M091(T) was 34.4 mol%
      and the major respiratory quinone was MK-6. Based on phenotypic and genotypic
      data, strain M091(T) represents a new genus and novel species in the family
      Flavobacteriaceae, for which the name Postechiella marina gen. nov., sp. nov. is
      proposed. The type strain of the type species is M091(T) (=KCTC 23537(T)=JCM
      17630(T)).

PMID- 21856981
TI  - Candida amazonensis sp. nov., an ascomycetous yeast isolated from rotting wood in
      the Amazonian forest.
AB  - Five strains of a novel yeast species were isolated from rotting wood samples
      collected in an Amazonian forest site in the state of Roraima, northern Brazil.
      The sequences of the D1/D2 domains of the large subunit of the rRNA gene showed
      that this species belongs to the Scheffersomyces clade and is related to Candida
      coipomoensis, Candida lignicola and Candida queiroziae. The novel species Candida
      amazonensis sp. nov. is proposed to accommodate these isolates. The type strain
      of C. amazonensis sp. nov. is UFMG-HMD-26.3(T) ( = CBS 12363(T) = NRRL Y
      48762(T)).

PMID- 21856982
TI  - Enterococcus plantarum sp. nov., isolated from plants.
AB  - Eight Gram-positive, catalase-negative bacterial strains were isolated during
      screening of enterococcal populations on plants. rep-PCR fingerprinting using the
      (GTG)(5) primer showed that the isolates constituted a single cluster that was
      separate from all known enterococcal species. 16S rRNA gene sequence phylogenetic
      analysis of three representative strains showed that the isolates belonged to the
      genus Enterococcus and that they clustered with the Enterococcus faecalis species
      group. Sequencing of the genes for the phenylalanyl-tRNA synthase alpha subunit
      (pheS) and the RNA polymerase alpha subunit (rpoA) also revealed the isolates'
      separate taxonomic position. Application of whole-cell protein fingerprinting,
      automated ribotyping and extensive phenotyping demonstrated the genetic and
      phenotypic homogeneity of the isolates and confirmed their separate position
      within the E. faecalis species group. The isolates represent a novel species of
      the genus Enterococcus, for which the name Enterococcus plantarum sp. nov. is
      proposed; the type strain is CCM 7889(T) (=LMG 26214(T)=C27(T)).

PMID- 21856983
TI  - Oceanisphaera sediminis sp. nov., isolated from marine sediment.
AB  - Two strains, designated TW92(T) and TW93, were isolated from marine sediment
      collected from the south coast of Korea. Cells of both strains were Gram-staining
      negative, coccus-shaped, aerobic, motile and catalase- and oxidase-positive.
      Strain TW92(T) grew optimally in the presence of 2 % (w/v) NaCl (range 1-5%)
      while strain TW93 grew optimally in the presence of 1% (w/v) NaCl (range 0-12%),
      and both strains had an optimal growth temperature of 30  degrees C (range 4-37 
      degrees C). Strains TW92(T) and TW93 had the same optimum pH (pH 7), but differed
      in their ability to grow at pH 10. Phylogenetic analysis based on 16S rRNA gene
      sequence similarity showed that strains TW92(T) and TW93 were most closely
      related to Oceanisphaera donghaensis BL1(T), with 98.8% and 98.7% similarity,
      respectively. Pairwise similarity between the 16S rRNA gene sequences of strains
      TW92(T) and TW93 was 99.9%. The major fatty acids of both strains were summed
      features 3 (comprising C(16:1)omega7c/iso-C(15) 2-OH), C(16:0) and
      C(18:1)omega7c. Both strains possessed the ubiquinone Q-8 as the predominant
      respiratory quinone and phosphatidylethanolamine, phosphatidylglycerol and
      diphosphatidylglycerol as the polar lipids. The genomic DNA G+C contents of
      strains TW92(T) and TW93 were 58.5 and 59.6 mol%, respectively. Genomic
      relatedness values based on DNA-DNA hybridization of strains TW92(T) and TW93
      with related species were below 47% and 31%, respectively. DNA-DNA hybridization
      values between strains TW92(T) and TW93 were above 85%. On the basis of a
      taxonomic study using polyphasic analysis, it is proposed that the two isolates
      represent a novel species, Oceanisphaera sediminis sp. nov., with strain TW92(T)
      (=KACC 15117(T)=JCM 17329(T)) as the type strain and strain TW93 (=KACC 15118=JCM
      17330) as an additional strain.

PMID- 21856984
TI  - Acidicapsa borealis gen. nov., sp. nov. and Acidicapsa ligni sp. nov.,
      subdivision 1 Acidobacteria from Sphagnum peat and decaying wood.
AB  - Two strains of subdivision 1 Acidobacteria, a pink-pigmented bacterium KA1(T) and
      a colourless isolate WH120(T), were obtained from acidic Sphagnum peat and wood
      under decay by the white-rot fungus Hyploma fasciculare, respectively. Cells of
      these isolates were Gram-negative-staining, non-motile, short rods, which were
      covered by large polysaccharide capsules and occurred singly, in pairs, or in
      short chains. Strains KA1(T) and WH120(T) were strictly aerobic mesophiles that
      grew between 10 and 33  degrees C, with an optimum at 22-28  degrees C. Both
      isolates developed under acidic conditions, but strain WH120(T) was more
      acidophilic (pH growth range 3.5-6.4; optimum, 4.0-4.5) than strain KA1(T) (pH
      growth range 3.5-7.3; optimum , 5.0-5.5). The preferred growth substrates were
      sugars. In addition, the wood-derived isolate WH120(T) grew on oxalate, lactate
      and xylan, while the peat-inhabiting acidobacterium strain KA1(T) utilized
      galacturonate, glucuronate and pectin. The major fatty acids were iso-C(15:0) and
      iso-C(17:1)omega8c; the cells also contained significant amounts of 13,16
      dimethyl octacosanedioic acid. The quinone was MK-8. The DNA G+C contents of
      strains KA1(T) and WH120(T) were 54.1 and 51.7 mol%, respectively. Strains KA1(T)
      and WH120(T) displayed 97.8% 16S rRNA gene sequence similarity to each other. The
      closest recognized relatives were Acidobacterium capsulatum and Telmatobacter
      bradus (93.4-94.3% 16S rRNA gene sequence similarity). These species differed
      from strains KA1(T) and WH120(T) by their ability to grow under anoxic
      conditions, the absence of capsules, presence of cell motility and differing
      fatty acid composition. Based on these differences, the two new isolates are
      proposed as representing a novel genus, Acidicapsa gen. nov., and two novel
      species. Acidicapsa borealis gen. nov., sp. nov. is the type species for the new
      genus with strain KA1(T) (=DSM 23886(T)=LMG 25897(T)=VKM B-2678(T)) as the type
      strain. The name Acidicapsa ligni sp. nov. is proposed for strain WH120(T) (=LMG
      26244(T)=VKM B-2677(T)=NCCB 100371(T)).

PMID- 21856985
TI  - Caloribacterium cisternae gen. nov., sp. nov., an anaerobic thermophilic
      bacterium from an underground gas storage reservoir.
AB  - A novel anaerobic, moderately thermophilic bacterium (strain SGL43(T)) was
      isolated from Severo-Stavropolskoye underground gas storage reservoir (Russia).
      Cells of strain SGL43(T) were motile straight rods, 0.4 um in diameter and 2.0
      3.0 um in length. The temperature range for growth was 28-65  degrees C, with
      optimum growth at 50  degrees C. The pH range for growth was 5.5-8.0, with
      optimum growth at pH 7.0-7.5. Growth of strain SGL43(T) was observed at NaCl
      concentrations of 0-4.0% (w/v) with optimum growth at 1.0% (w/v) NaCl. Substrates
      utilized by strain SGL43(T) included peptone, yeast extract, glucose, fructose,
      maltose, galactose, pyruvate and citrate. Products of glucose or citrate
      fermentation were acetate, hydrogen and CO(2). Thiosulfate was reduced to
      sulfide. The DNA G+C content of strain SGL43(T) was 43.1 mol%. 16S rRNA gene
      sequence analysis revealed that strain SGL43(T) belongs to the order
      Thermoanaerobacterales (phylum 'Firmicutes'). The closest relative of strain
      SGL43(T) was Thermoanaerobacterium saccharolyticum (86.2% 16S rRNA gene sequence
      similarity with the type strain). Based on the data presented here, strain
      SGL43(T) is considered to represent a novel species of a new genus, for which the
      name Caloribacterium cisternae gen. nov., sp. nov. is proposed. The type strain
      of Caloribacterium cisternae, the type species of the genus, is SGL43(T) (=DSM
      23830(T)=VKM B-2670(T)).

PMID- 21856986
TI  - Sphingobacterium lactis sp. nov. and Sphingobacterium alimentarium sp. nov.,
      isolated from raw milk and a dairy environment.
AB  - Four non-fermenting, rod-shaped, Gram-staining-negative bacterial strains,
      designated WCC 4512(T), WS 4555, WCC 4521(T) and WS 4556, were isolated from raw
      milk and the dairy environment. Phylogenetic analyses based on 16S rRNA and groEL
      gene sequences demonstrated the affiliation of the four strains to two distinct
      clusters within the class Sphingobacteriia, phylum 'Bacteroidetes'. Strains WCC
      4512(T) and WS 4555 showed the highest 16S rRNA gene sequence similarity to the
      type strain of S. daejeonense (97.3 and 97.2%, respectively), whereas strains WCC
      4521(T) and WS 4556 were most closely related to S. composti LMG 23401(T) (97.6%
      16S rRNA gene sequence similarity). The DNA G+C contents of strains WCC 4512(T)
      and WCC 4521(T) were 44.2 and 39.3 mol%, respectively. The major cellular fatty
      acids and the presence of menaquinone MK-7 as the predominant quinone for both
      strains WCC 4512(T) and WCC 4521(T) supported their affiliation to the genus
      Sphingobacterium. DNA-DNA hybridization experiments between strain WCC 4512(T)
      and S. daejeonense LMG 23402(T) and between strain WCC 4521(T) and S. composti
      LMG 23401(T) revealed DNA relatedness values of 2% (repetition, 3%) and 8%
      (repetition, 17%), respectively. On the basis of phenotypic and genetic
      properties, as well as phylogenetic distinctiveness, it is suggested that the
      four strains represent two novel Sphingobacterium species with strain WCC 4512(T)
      (=DSM 22361(T)=LMG 25272(T)) as the type strain of Sphingobacterium lactis sp.
      nov. (WS 4555 is a reference strain of S. lactis) and strain WCC 4521(T) (=DSM
      22362(T)=LMG 25273(T)) as the type strain of Sphingobacterium alimentarium sp.
      nov. (WS 4556 is a reference strain of S. alimentarium).

PMID- 21856987
TI  - Thermus composti sp. nov., isolated from oyster mushroom compost.
AB  - A Gram-stain-negative, rod-shaped bacterium (strain K-39(T)) was isolated from
      the thermophilic phase of the composting process for oyster mushroom substrate
      preparation. The strain grew at 40-80  degrees C (optimum, 65-75  degrees C), at
      pH 5-9 (optimum, pH 7), in media containing up to 1.5% (w/v) NaCl. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain K-39(T) formed a
      distinct lineage within the genus Thermus. Its closest cultivated relative was
      Thermus islandicus PRI 3838(T) (96.8% similarity). The DNA G+C content of strain
      K-39(T) was 71.3 mol%. The new strain could be differentiated from the related
      taxa by not being able to hydrolyse starch. The predominant fatty acids of strain
      K-39(T) were iso-C(17:0) and anteiso-C(17:0). Strain K-39(T) contained a lower
      amount of the fatty acid iso-C(15:0) as compared to related species of the genus
      Thermus. The predominant respiratory quinone of the new isolate was menaquinone
      MK-8. On the basis of a taxonomic study using a polyphasic approach, strain K
      39(T) is considered to represent a novel species of the genus Thermus, for which
      the name Thermus composti sp. nov. is proposed. The type strain is K-39(T) (=DSM
      21686(T)=NCAIM B 02340(T)).

PMID- 21856988
TI  - Taxonomic revision of the genus Geobacillus: emendation of Geobacillus, G.
      stearothermophilus, G. jurassicus, G. toebii, G. thermodenitrificans and G.
      thermoglucosidans (nom. corrig., formerly 'thermoglucosidasius'); transfer of
      Bacillus thermantarcticus to the genus as G. thermantarcticus comb. nov.;
      proposal of Caldibacillus debilis gen. nov., comb. nov.; transfer of G.
      tepidamans to Anoxybacillus as A. tepidamans comb. nov.; and proposal of
      Anoxybacillus caldiproteolyticus sp. nov.
AB  - Sixty-two strains of thermophilic aerobic endospore-forming bacteria were
      subjected to polyphasic taxonomic study including 16S rRNA gene sequence
      analysis, polar lipid and fatty acid analysis, phenotypic characterization, and
      DNA-DNA hybridization experiments. Distinct clusters of the species Geobacillus
      stearothermophilus, Geobacillus thermodenitrificans, Geobacillus toebii and
      Geobacillus thermoglucosidasius were formed, allowing their descriptions to be
      emended, and the distinctiveness of the poorly represented species Geobacillus
      jurassicus, Geobacillus subterraneus and Geobacillus caldoxylosilyticus was
      confirmed. It is proposed that the name Geobacillus thermoglucosidasius be
      corrected to Geobacillus thermoglucosidans nom. corrig. Bacillus thermantarcticus
      clustered between Geobacillus species on the basis of 16S rRNA gene sequence
      analysis, and its transfer to the genus Geobacillus as Geobacillus
      thermantarcticus comb. nov. (type strain LMG 23032(T)=DSM 9572(T)=strain M1(T)=R
      35644(T)) is proposed. The above-mentioned species, together with Geobacillus
      thermoleovorans and Geobacillus thermocatenulatus, form a monophyletic cluster
      representing the genus Geobacillus. The distinctiveness of 'Geobacillus
      caldoproteolyticus' was confirmed and it is proposed that it be accommodated,
      along with Geobacillus tepidamans, in the genus Anoxybacillus as Anoxybacillus
      caldiproteolyticus sp. nov. (type strain DSM 15730(T)=ATCC BAA-818(T)=LMG
      26209(T)=R-35652(T)) and Anoxybacillus tepidamans comb. nov. (type strain LMG
      26208(T)=ATCC BAA-942(T)=DSM 16325(T)=R-35643(T)), respectively. The type strain
      of Geobacillus debilis was not closely related to any members of the genera
      Anoxybacillus and Geobacillus, and it is proposed that this species be placed in
      the new genus Caldibacillus as Caldibacillus debilis gen. nov. comb. nov. The
      type strain of the type species, Caldibacillus debilis, is LMG 23386(T) (=DSM
      16016(T)=NCIMB 13995(T)=Tf(T)=R-35653(T)).

PMID- 21856990
TI  - Fatigue perceived by multiple sclerosis patients is associated with muscle
      fatigue.
AB  - BACKGROUND: Fatigue is a debilitating symptom in multiple sclerosis (MS).
      Previous studies showed no association between fatigue as perceived by the
      patient and physiological measures of fatigability. OBJECTIVE: The authors
      investigated associations between perceived fatigue and measures of fatigability
      after correction for differences in maximal voluntary contraction (MVC). METHODS:
      A total of 20 people with relapsing-remitting MS with an Extended Disability
      Severity Score less than 5.5 and 20 healthy controls filled out the Fatigue
      Severity Score questionnaire of perceived fatigue. The authors obtained the MVC
      from the first dorsal interosseus muscle, voluntary muscle activation, and force
      decline during a sustained MVC (124 s, muscle fatigue). RESULTS: Patients
      perceived increased levels of fatigue compared with controls (P < .001). Although
      patients and controls developed similar amounts of muscle fatigue during the
      sustained contraction, a linear regression model that included both muscle
      fatigue and MVC was positively associated with perceived fatigue in patients only
      (R (2) = 0.45; P = .01). Voluntary activation during the sustained contraction
      was negatively associated with perceived fatigue (R (2) = 0.25; P = .02).
      CONCLUSION: The data indicate that fatigue perceived by MS patients is associated
      with measures of fatigability. This observation helps in the understanding of
      mechanisms underlying the increased levels of fatigue perceived by MS patients.
      These data also emphasize that for comparison of fatigue-related parameters
      between groups, correction for individual maximal force is essential.

PMID- 21856989
TI  - Melghirimyces algeriensis gen. nov., sp. nov., a member of the family
      Thermoactinomycetaceae, isolated from a salt lake.
AB  - A novel filamentous bacterium, designated NariEX(T), was isolated from soil
      collected from Chott Melghir salt lake, which is located in the south-east of
      Algeria. The strain was an aerobic, halotolerant, thermotolerant, Gram-positive
      bacterium that was able to grow in NaCl concentrations up to 21% (w/v), at 37-60 
      degrees C and at pH 5.0-9.5. The major fatty acids were iso- and anteiso-C(15:0).
      The DNA G+C content was 47.3 mol%. The major menaquinone was MK-7, but MK-6 and
      MK-8 were also present. The polar lipid profile consisted of
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylmonomethylethanolamine (methyl-PE). Results of molecular and
      phenotypic analysis led to the description of the strain as a new member of the
      family Thermoactinomycetaceae. The isolate was distinct from members of
      recognized genera of this family by morphological, biochemical and chemotaxonomic
      characteristics. Strain NariEX(T) showed 16S rRNA gene sequence similarities of
      95.38 and 94.28% with the type strains of Desmospora activa and Kroppenstedtia
      eburnea, respectively, but differed from both type strains in its sugars, polar
      lipids and in the presence of methyl-PE. On the basis of physiological and
      phylogenetic data, strain NariEX(T) represents a novel species of a new genus of
      the family Thermoactinomycetaceae for which the name Melghirimyces algeriensis
      gen. nov., sp. nov. is proposed. The type strain of Melghirimyces algeriensis,
      the type species of the genus, is NariEX(T) (=DSM 45474(T)=CCUG 59620(T)).

PMID- 21856991
TI  - Kindergarten children's growth trajectories in reading and mathematics: who falls
      increasingly behind?
AB  - The authors used a large sample of children (N ~ 7,400) participating in the
      Early Childhood Longitudinal Study--Kindergarten Cohort (ECLS-K) to estimate
      kindergarten children's academic achievement growth trajectories in reading and
      mathematics. The authors were particularly interested in whether the growth
      trajectories of children with learning disabilities (LD) or speech language
      impairments (SLI)--as well as those of other groups of children--were consistent
      with a cumulative or compensatory developmental cycle. Both LD and SLI children
      displayed significantly lower levels of kindergarten reading achievement than
      nondisabled children. However, and over the subsequent 5 years of elementary
      school, only children with SLI lagged increasingly behind nondisabled peers in
      their reading skills growth. The authors observed a different pattern for
      mathematics achievement. Children with LD, but not SLI, lagged increasingly
      behind nondisabled children in their mathematics skills growth. The authors also
      observed some consistency in "poor-get-poorer" effects across reading and
      mathematic achievement for additional population subgroups. Those kindergarten
      children who were from lower socioeconomic status families, who were African
      American, and who more frequently displayed learning-related behavior problems
      initially had lower levels of reading and mathematics achievement and also lagged
      increasingly behind in their acquisition of these skills over time. Some groups
      of children, including those with SLI, experience a cumulative rather than a
      compensatory cycle of achievement growth.

PMID- 21856992
TI  - Matthew effects in reading comprehension: myth or reality?
AB  - The presence of Matthew effects was tested in students of varying reading,
      spelling, and vocabulary skills. A cross-sequential design was implemented,
      following 587 Grade 2 through 4 students across five measurement points (waves)
      over 2 years. Students were administered standardized assessments of reading,
      spelling, and vocabulary. Results indicated that the hypothesized fan-spread
      pattern for Matthew effects was not evident. Low and high ability groups were
      formed based on 25th and 75th percentile cutoffs on initial measures of spelling,
      reading accuracy and fluency, vocabulary, and reading comprehension. Multilevel
      modeling suggested that low and high ability groups had significantly different
      starting points (intercepts) and their pattern of growth on passage comprehension
      did not indicate that the gap would increase over time. Instead, some analyses,
      especially of the youngest cohorts, showed significant convergence. However,
      there was no evidence of eventually closing the gap. Thus, although the poor
      students may not be getting poorer, they do not get sufficiently richer either.

PMID- 21856993
TI  - Fullerene c60: inhalation hazard assessment and derivation of a period-limited
      acceptable exposure level.
AB  - Fullerene C(60) has great potential for use in many industry and medical
      nanotechnology applications. Although the use of nanomaterials has been
      increasing in the recent years, limited information about its potential hazardous
      effects is available. Therefore, safety of nanomaterials is a world concern.
      Before health effects arise in workers and the general population, development
      and use under appropriate management are desirable. Therefore, we aimed to
      determine an acceptable exposure level for humans by reviewing the limited animal
      toxicity data available. Here, we present an initial hazard assessment, including
      a review of the available toxicity information of the effects of C(60) on the
      lungs. We then estimated the no-observed-adverse-effect level (NOAEL) of C(60) on
      rat lung toxicity by using lung retention of C(60) in inhalation exposure and
      intratracheal instillation tests. The NOAEL of C(60) on rat lung toxicity was
      estimated to be 3.1 mg/m(3). Because this is the NOAEL for subchronic toxicity, a
      period-limited acceptable exposure level (AEL(PL)) for humans was proposed, which
      assumed 15 years of exposure and modification within the next 10 years since more
      knowledge will be gained in the future. The AEL(PL) of C(60) particles with a
      geometric mean of 96 nm and a geometric standard deviation (GSD) of 2.0 was
      estimated to be 0.39 mg/m(3) for healthy workers and 1.4 * 10(-2) mg/m(3) for the
      general human population. The AEL(PL) of C(60) particles with different sizes was
      estimated to be   for healthy workers and   for the general human population.

PMID- 21856994
TI  - The Princess Marina Hospital accident and emergency triage scale provides highly
      reliable triage acuity ratings.
AB  - OBJECTIVE: To determine the interrater reliability of triage acuity ratings by
      healthcare workers (HCW) using a previous triage system (PTS) and the Princess
      Marina Hospital accident and emergency centre triage scale (PATS), a local
      adaptation of the widely used and studied South African triage scale. METHODS: A
      cross-sectional study was performed on HCW in an emergency department (ED) in
      Botswana to determine the interrater reliability of triage acuity ratings when
      using PTS and PATS to assign triage categories to 25 written vignettes after PATS
      training. The intraclass correlation coefficient (ICC) was calculated to assess
      interrater reliability, and graphic displays were used to portray rating
      distributions for vignettes with a mean rating of different acuity categories for
      PTS and PATS. RESULTS: 44 HCW completed the scenarios. The ICC for the group of
      HCW was 0.52 (95% CI 0.37 to 0.67) using PTS and 0.87 (95% CI 0.80 to 0.93) using
      PATS. The ICC values were higher for PATS than PTS regardless of the number of
      years of experience of the HCW and the level of the HCW (specialist, medical
      officer, nurse, nurse aide). Graphic displays showed that there was less
      variability at all acuity levels when using PATS compared with PTS. CONCLUSION:
      The reliability measures in this study indicate very high interrater agreement
      and limited variability in acuity ratings when using the PATS as opposed to
      moderate agreement and increased variability in acuity ratings when using PTS.
      This suggests that PATS is reliably applied by all levels of HCW and supports the
      feasibility of the further implementation of PATS in ED in Botswana and in other
      similar settings.

PMID- 21856995
TI  - Human polymorphisms at long non-coding RNAs (lncRNAs) and association with
      prostate cancer risk.
AB  - Long non-coding RNAs (lncRNAs), representing a large proportion of non-coding
      transcripts across the human genome, are evolutionally conserved and biologically
      functional. At least one-third of the phenotype-related loci identified by genome
      wide association studies (GWAS) are mapped to non-coding intervals. However, the
      relationships between phenotype-related loci and lncRNAs are largely unknown.
      Utilizing the 1000 Genomes data, we compared single-nucleotide polymorphisms
      (SNPs) within the sequences of lncRNA and protein-coding genes as defined in the
      Ensembl database. We further annotated the phenotype-related SNPs reported by
      GWAS at lncRNA intervals. Because prostate cancer (PCa) risk-related loci were
      enriched in lncRNAs, we then performed meta-analysis of two existing GWAS for
      discovery and an additional sample set for replication, revealing PCa risk
      related loci at lncRNA regions. The SNP density in regions of lncRNA was similar
      to that in protein-coding regions, but they were less polymorphic than
      surrounding regions. Among the 1998 phenotype-related SNPs identified by GWAS, 52
      loci were located directly in lncRNA intervals with a 1.5-fold enrichment
      compared with the entire genome. More than a 5-fold enrichment was observed for
      eight PCa risk-related loci in lncRNA genes. We also identified a new PCa risk
      related SNP rs3787016 in an lncRNA region at 19q13 (per allele odds ratio = 1.19;
      95% confidence interval: 1.11-1.27) with P value of 7.22 * 10(-7). lncRNAs may be
      important for interpreting and mining GWAS data. However, the catalog of lncRNAs
      needs to be better characterized in order to fully evaluate the relationship of
      phenotype-related loci with lncRNAs.

PMID- 21856997
TI  - ERbeta-specific agonists and genistein inhibit proliferation and induce apoptosis
      in the large and small intestine.
AB  - Epidemiological data indicate that intake of estrogens and isoflavones may be
      beneficial for the prevention of colorectal cancer (CRC). Based on this data, the
      aim of the study was to investigate estrogen receptor (ER) subtype-specific
      effects on intestinal homeostasis. Ovariectomized (OVX) female Wistar rats were
      either treated with 17beta-estradiol (4 MUg/kg body wt/day) (E2), an ERalpha
      specific agonist (ALPHA) (10 MUg/kg body wt/day), an ERbeta-specific agonist
      (BETA) (100 MUg/kg body wt/day) or genistein (GEN) (10 mg/kg body wt/day) for
      three weeks. Vehicle-treated OVX and SHAM animals and those cotreated with BETA
      and the pure antiestrogen Fulvestrant (ICI 182780) (100 MUg/kg body wt/day and 3
      mg/kg body wt/day) served as controls. GEN and BETA treatment but not E2 and
      ALPHA administration reduced proliferation in ileal and colonic mucosa cells. The
      rate of apoptosis in the small intestine and colon was increased by treatment
      with BETA and GEN, but not by E2. BETA induced antiproliferative and proapoptotic
      activity also in SHAM animals. The effects were antagonized by the pure
      antiestrogen Fulvestrant. Polymerase chain reaction gene array analysis revealed
      that BETA resulted in the downregulation of the oncogene transformation-related
      protein 63 (p63). Our data indicate that activation of the ERbeta by specific
      ERbeta agonists and GEN induces antiproliferative and proapoptotic effects in the
      intestinal tract. This observation can be taken as an indication that intake of
      GEN and specific ERbeta agonists may protect the ileal and colonic epithelium
      from tumor development via modulation of tissue homeostasis.

PMID- 21856996
TI  - Green tea consumption and colorectal cancer risk: a report from the Shanghai
      Men's Health Study.
AB  - Tea and its constituents have demonstrated anticarcinogenic activity in both in
      vitro and in vivo animal studies. Results from epidemiologic studies, however,
      have been inconsistent. Some factors that coexist with tea consumption, such as
      cigarette smoking, may confound or modify the association between tea consumption
      and cancer risk. The objective of this study was to comprehensively evaluate the
      association between green tea consumption and colorectal cancer risk in a
      population-based prospective cohort study, the Shanghai Men's Health Study. The
      analysis included 60,567 Chinese men aged 40-74 years at baseline. During ~5
      years of follow-up, 243 incident cases of colorectal cancer were identified.
      Multivariable Cox regression models were used to estimate hazard ratios (HRs) and
      95% confidence intervals (CIs) of developing colorectal cancer. Regular green tea
      consumption (ever drank green tea at least three times per week for more than six
      consecutive months) was associated with reduced risk of colorectal cancer in non
      smokers (multivariable-adjusted HR = 0.54, 95% CI: 0.34-0.86). The risk decreased
      as the amount of green tea consumption increased (P(trend) = 0.01). Each 2 g
      increment of intake of dry green tea leaves per day (approximately equivalent to
      the amount of tea in a tea bag) was associated with a 12% reduction in risk (HR =
      0.88, 95% CI: 0.78-0.99). No significant association was found among smokers (HR
      = 0.94, 95% CI: 0.66-1.34). This study suggests that regular consumption of green
      tea may reduce colorectal cancer risk among non-smokers.

PMID- 21856998
TI  - Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.
AB  - Clinical experience with hydroxocobalamin in acute cyanide poisoning via
      ingestion remains limited. This case concerns a 35-year-old mentally ill woman
      who consumed more than 20 apricot kernels. Published literature suggests each
      kernel would have contained cyanide concentrations ranging from 0.122 to 4.09
      mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a
      raised pulse rate and slight metabolic acidosis. Forty minutes after admission
      (approximately 70 min postingestion), the patient experienced headache, nausea
      and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment
      with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This
      prompted the administration of oxygen, which evoked a slight improvement in her
      vital signs. Hydroxocobalamin was then administered. After 24 h, she was
      completely asymptomatic with normalised blood pressure and other haemodynamic
      parameters. This case reinforces the safety and effectiveness of hydroxocobalamin
      in acute cyanide poisoning by ingestion.

PMID- 21857000
TI  - Towards evidence based emergency medicine: PRIVATE Best BETs from the Manchester
      Royal Infirmary. BET 1: Can the nature and extent of orbital trauma be optimally
      assessed with ultrasound imaging in the emergency department?

PMID- 21856999
TI  - An elderly woman with increasing dyspnoea after a fall.
AB  - An otherwise healthy 92-year-old woman was admitted to our department with
      shortness of breath and dysphagia 10 h after a fall in her bathroom. Medical
      checkup at another institution had not uncovered the causation of the complaints.
      Clinical and radiological examinations at our department then revealed an
      expanding retropharyngeal and prevertebral haematoma. Because of increasing
      dyspnoea, a lateral cervical approach was used to remove the haematoma and to
      achieve haemostasis. The authors could demonstrate that the source of bleeding
      was a minor injury of the anterior longitudinal ligament. Retropharyngeal
      haematoma is a potentially life-threatening condition because it can rapidly
      progress to airway obstruction. Large retropharyngeal haematoma after minor blunt
      head and neck trauma is not a well-recognised condition. This case, however,
      illustrates that precarious retropharyngeal haematoma can occur after low-energy
      trauma even without anticoagulation therapy. A high index of suspicion for this
      airway collapse is advisable in older patients.

PMID- 21857002
TI  - Towards evidence based emergency medicine: PRIVATE Best BETs from the Manchester
      Royal Infirmary. BET 2: Use of end-tidal carbon dioxide indicators in prehospital
      intubations will reduce the number of incorrectly placed endotracheal tubes.

PMID- 21857003
TI  - Towards evidence based emergency medicine: PRIVATE Best BETs from the Manchester
      Royal Infirmary. BET 3: Do head elevation and neck flexion improve laryngeal view
      and the likelihood of successful intubation.

PMID- 21857004
TI  - Towards evidence based emergency medicine: PRIVATE Best BETs from the Manchester
      Royal Infirmary. BET 4: Are meningeal irritation signs reliable in diagnosing
      meningitis in children?

PMID- 21857006
TI  - Chromosomal aberrations involving telomeres and interstitial telomeric sequences.
AB  - Telomeres are specialised nucleoproteic complexes localised at the physical ends
      of linear eukaryotic chromosomes that maintain their stability and integrity. In
      vertebrate chromosomes, the DNA component of telomeres is constituted by
      (TTAGGG)n repeats, which can be localised at the terminal regions of chromosomes
      (true telomeres) or at intrachromosomal sites (interstitial telomeric sequences
      or ITSs, located at the centromeric region or between the centromere and the
      telomere). In the past two decades, the use of molecular cytogenetic techniques
      has led to a new spectrum of spontaneous and clastogen-induced chromosomal
      aberrations being identified, involving telomeres and ITSs. Some aberrations
      involve the chromosome ends and, indirectly, the telomeric repeats located at the
      terminal regions of chromosomes (true telomeres). A second type of aberrations
      directly involves the telomeric sequences located at the chromosome ends.
      Finally, there is a third class of aberrations that specifically involves the
      ITSs. The aims of this review are to provide a detailed description of these
      aberrations and to summarise the available data regarding their induction by
      physical and chemical mutagens.

PMID- 21857008
TI  - Testing the hypothesis that formal thought disorders are severe mood disorders.
AB  - BACKGROUND: It was recently hypothesized by Lake (Schizophrenia Bulletin 2008;
      34: 109-117) that Formal Thought Disorder (FTD) can be accounted for by a single
      disorder that is currently diagnosed as bipolar disorder. OBJECTIVES: This study
      aimed to analyze the underlying dimensions of FTD and to examine to what extent
      FTD factors can be accounted for by clinical distractibility, attentional
      impairment, severity of mania, and familial liability of bipolar disorder and
      schizophrenia. METHODS: Six hundred and sixty inpatients were assessed using a
      semistructured interview, and FTDs were assessed with the Thought, Language, and
      Communication scale. "Inattentiveness during Mental Status Testing" item of the
      Scale for the Assessment of Negative Symptoms scale and a composite mania score
      were used. The Family History-Research Diagnostic Criteria was used. RESULTS: FTD
      is a multidimensional construct comprised at least 5 dimensions: disorganization,
      verbosity, poverty of speech, idiosyncratic thinking, and blocking. Clinical
      distractibility loadings split in 2 factors, disorganization and blocking, but it
      did not load on the mania-related (verbosity) factor. Attentional disturbance was
      significantly associated with each FTD factor except for idiosyncratic thinking,
      and these associations were largely independent from the severity of mania. The
      associations of FTDs with mania and attentional disturbances were independent
      from each other. FTD factors were not significantly associated with familial
      liability to bipolar or to schizophrenia. CONCLUSIONS: Disorganization was the
      main FTD component. Distractibility was a core feature of FTD factors but it was
      not specifically accounted for by mania-related attentional impairment. The
      hypothesis of mutual interdependence between mania and attentional disturbance
      leading to FTDs could not be confirmed.

PMID- 21857007
TI  - Diet-related telomere shortening and chromosome stability.
AB  - Recent evidences have highlighted an influence of micronutrients in the
      maintenance of telomere length (TL). In order to explore whether diet-related
      telomere shortening had any physiological relevance and was accompanied by
      significant damage in the genome, in the present study, TL was assessed by
      terminal restriction fragment (TRF) analysis in peripheral blood lymphocytes of
      56 healthy subjects for which detailed information on dietary habits was
      available and data were compared ?with the incidence of nucleoplasmic bridges
      (NPBs), a marker of chromosomal instability related to telomere dysfunction
      visualised with the cytokinesis-blocked micronucleus assay. To increase the
      capability to detect even slight impairment of telomere function, the incidence
      of NPBs was also evaluated on cells exposed in vitro to ionising radiation. Care
      was taken to control for potential confounding factors that might influence TL,
      viz. age, hTERT genotype and smoking status. Data showed that higher consumption
      of vegetables was related with significantly higher mean TL (P = 0.013); in
      particular, the analysis of the association between micronutrients and mean TL
      highlighted a significant role of antioxidant intake, especially beta-carotene,
      on telomere maintenance (P = 0.004). However, the diet-related telomere
      shortening did not result in associated increased spontaneous or radiation
      induced NPBs. The distribution of TRFs was also analysed and a slight prevalence
      of radiation-induced NPBs (P = 0.03) was observed in subjects with higher amount
      of very short TRFs (<2 kb). The relative incidence of very short TRFs was
      positively associate with ageing (P = 0.008) but unrelated to vegetables
      consumption and daily intake of micronutrients, suggesting that the degree of
      telomere erosion related with low dietary intake of antioxidants observed in this
      study was not so extensive to lead to chromosome instability.

PMID- 21857009
TI  - How genes and environmental factors determine the different neurodevelopmental
      trajectories of schizophrenia and bipolar disorder.
AB  - The debate endures as to whether schizophrenia and bipolar disorder are separate
      entities or different manifestations of a single underlying pathological process.
      Here, we argue that this sterile argument obscures the fact that the truth lies
      somewhere in between. Thus, recent studies support a model whereby, on a
      background of some shared genetic liability for both disorders, patients with
      schizophrenia have been subject to additional genetic and/or environmental
      factors that impair neurodevelopment; for example, copy number variants and
      obstetric complications are associated with schizophrenia but not with bipolar
      disorder. As a result, children destined to develop schizophrenia show an excess
      of neuromotor delays and cognitive difficulties while those who later develop
      bipolar disorder perform at least as well as the general population. In keeping
      with this model, cognitive impairments and brain structural abnormalities are
      present at first onset of schizophrenia but not in the early stages of bipolar
      disorder. However, with repeated episodes of illness, cognitive and brain
      structural abnormalities accumulate in both schizophrenia and bipolar disorder,
      thus clouding the picture.

PMID- 21857010
TI  - Confidence of trainee doctors in the management of diabetes.

PMID- 21857011
TI  - Successful childbirth after intracytoplasmic morphologically selected sperm
      injection without assisted oocyte activation in a patient with globozoospermia.
AB  - We here report a successful pregnancy and healthy childbirth obtained in a case
      of total globozoospermia after intracytoplasmic morphologically selected sperm
      injection (IMSI) without assisted oocyte activation (AOA). Two semen analyses
      showed 100% globozoospermia on classic spermocytogram. Motile sperm organelle
      morphology examination (MSOME) analysis at *10,000 magnification confirmed the
      round-headed aspect for 100% of sperm cells, but 1% of the spermatozoa seemed to
      present a small bud of acrosome. This particular aspect was confirmed by
      transmission electron microscopy and anti-CD46 staining analysis. Results from
      sperm DNA fragmentation and fluorescence in situ hybridization analyses were
      normal. The karyotype was 46XY, and no mutations or deletions in SPATA16 and
      DPY19L2 genes were detected. Considering these results, a single IMSI cycle was
      performed, and spermatozoa were selected for the absence of vacuoles and the
      presence of a small bud of acrosome. A comparable fertilization rate with or
      without calcium-ionophore AOA was observed. Two fresh top-quality embryos
      obtained without AOA were transferred at Day 2 after IMSI, leading to pregnancy
      and birth of a healthy baby boy. This successful outcome suggests that MSOME may
      be useful in cases of globozoospermia in order to carefully evaluate sperm
      morphology and to maximize the benefit of ICSI/IMSI.

PMID- 21857012
TI  - Angiography-based prediction of outcome after coronary artery bypass surgery
      versus changes in myocardial perfusion scintigraphy.
AB  - OBJECTIVES: The present study compared the clinical prediction of the effect of
      coronary artery bypass grafting (CABG) on coronary blood flow and left
      ventricular ejection fraction (LVEF) with changes in gated myocardial perfusion
      scintigraphy. METHODS: A prospective group of 92 patients underwent myocardial
      perfusion scintigraphy before and 6 months after CABG, the results being kept
      secret from the surgeon. Based on clinical and angiographic findings, the
      surgeons filled in a questionnaire indicating the predicted changes in coronary
      blood flow in each of the three coronary artery territories and in the LVEF.
      RESULTS: Symptomatic improvement was present in nearly all the patients.
      Following CABG, the perfusion defects were reduced in around two-thirds and
      normalized in one-third of the territories clinically predicted to improve.
      Improved perfusion for territories not predicted to improve was slightly lower,
      and correlations between predicted and observed regional changes in coronary
      blood flow and perfusion defects were poor. LVEF increased (by over five ejection
      fraction units) in almost half of the patients, but with no correlation between
      the predicted and the observed changes. CONCLUSIONS: Based on clinical and
      angiographic findings, the marked improvements after CABG in cardiac perfusion
      and function are poorly predicted.

PMID- 21857013
TI  - Does a postoperative visit increase patient satisfaction with anaesthesia care?
AB  - BACKGROUND: 'Continuity of personal care by anaesthetist', as defined by a single
      anaesthetist providing preoperative evaluation, performing anaesthesia, and
      delivering a postoperative visit to the patient, has been shown to be a major
      factor for patient satisfaction with anaesthesia care. This prospective
      randomized study investigated whether a single postoperative visit increased the
      patient's perception of 'Continuity of personal care by anaesthetist' and hence
      satisfaction. METHODS: In Group 1, the same anaesthetist who conducted
      anaesthesia visited the patient on the first postoperative day. In Group 2, a
      nurse anaesthetist who did not participate in anaesthesia delivery made a
      postoperative visit to the patient. Patients in Group 3 were not visited.
      Patients received a previously validated questionnaire after discharge from
      hospital. RESULTS: The negative patient response created by the perception of not
      being visited after operation by the attending anaesthetist was 13.5% (95% CI +/-
      6.9), 69.2% (95% CI +/- 10.3), and 77.1% (95% CI +/- 9.1) in Groups 1, 2, and 3,
      respectively, with 1 vs 2 and 1 vs 3 (P < 0.001) being significantly different.
      The negative patient response for 'Continuity of personal care by anaesthetist'
      was 40.0% (95% CI +/- 5.3), 48.8% (95% CI +/- 5.6), and 55.5% (95% CI +/- 5.3) in
      Groups 1, 2, and 3, respectively, with 1 vs 3 (P < 0.001) being significantly
      different. CONCLUSIONS: Perception of the anaesthetist and satisfaction with
      'Continuity of personal care by anaesthetist' were significantly increased by the
      introduction of a single postoperative visit by the anaesthetist compared with no
      visit at all. Overall satisfaction with anaesthesia was unchanged.

PMID- 21857014
TI  - Switch from aprotinin to epsilon-aminocaproic acid: impact on blood loss,
      transfusion, and clinical outcome in neonates undergoing cardiac surgery.
AB  - BACKGROUND: With the withdrawal of aprotinin from worldwide marketing in November
      2007, many institutions treating patients at high risk for hyperfibrinolysis had
      to update their therapeutic protocols. At our institution, the standard was
      switched from aprotinin to epsilon-aminocaproic acid (EACA) in all patients
      undergoing cardiac surgery with extracorporeal circulation including neonates.
      Although both antifibrinolytic medications have been used widely for many years,
      there are few data directly comparing their blood-sparing effect and their side
      effects especially in neonates. METHODS: Perioperative data from 235 neonates
      aged up to 30 days undergoing primary cardiac surgery were analysed. Between July
      1, 2006 and November 5, 2007, all patients (n=95) received aprotinin. Starting
      November 6, 2007 until December 31, 2009, all patients (n=140) were treated with
      EACA. The primary outcome criterion was blood loss; secondary outcome criteria
      were transfusion requirements, renal, vascular, and neurological complications
      and also in-hospital mortality. RESULTS: All descriptive and intraoperative data
      variable were similar. Blood loss was significantly higher in the EACA group
      (P=0.001), but there was no difference in the rate of re-operation for bleeding
      (P=0.218) nor the number of transfusions. There were no differences in the
      incidences of postoperative renal, neurological, and vascular events or in
      hospital mortality. CONCLUSIONS: In neonatal patients undergoing cardiac surgery,
      the switch to EACA treatment led to a higher postoperative blood loss. However,
      there were no differences in transfusion requirements or major clinical outcomes.

PMID- 21857015
TI  - Resuscitation with hydroxyethyl starch improves renal function and lactate
      clearance in penetrating trauma in a randomized controlled study: the FIRST trial
      (Fluids in Resuscitation of Severe Trauma).
AB  - BACKGROUND: The role of fluids in trauma resuscitation is controversial. We
      compared resuscitation with 0.9% saline vs hydroxyethyl starch, HES 130/0.4, in
      severe trauma with respect to resuscitation, fluid volume, gastrointestinal
      recovery, renal function, and blood product requirements. METHODS: Randomized,
      controlled, double-blind study of severely injured patients requiring >3 litres
      of fluid resuscitation. Blunt and penetrating trauma were randomized separately.
      Patients were followed up for 30 days. RESULTS: A total of 115 patients were
      randomized; of which, 109 were studied. For patients with penetrating trauma
      (n=67), the mean (sd) fluid requirements were 5.1 (2.7) litres in the HES group
      and 7.4 (4.3) litres in the saline group (P<0.001). In blunt trauma (n=42), there
      was no difference in study fluid requirements, but the HES group required
      significantly more blood products [packed red blood cell volumes 2943 (1628) vs
      1473 (1071) ml, P=0.005] and was more severely injured than the saline group
      (median injury severity score 29.5 vs 18; P=0.01). Haemodynamic data were
      similar, but, in the penetrating group, plasma lactate concentrations were lower
      over the first 4 h (P=0.029) and on day 1 with HES than with saline [2.1 (1.4) vs
      3.2 (2.2) mmol litre-1; P=0.017]. There was no difference between any groups in
      time to recovery of bowel function or mortality. In penetrating trauma, renal
      injury occurred more frequently in the saline group than the HES group (16% vs
      0%; P=0.018). In penetrating trauma, maximum sequential organ function scores
      were lower with HES than with saline (median 2.4 vs 4.5, P=0.012). No differences
      were seen in safety measures in the blunt trauma patients. CONCLUSIONS: In
      penetrating trauma, HES provided significantly better lactate clearance and less
      renal injury than saline. No firm conclusions could be drawn for blunt trauma.
      STUDY REGISTRATION: ISRCTN 42061860.

PMID- 21857016
TI  - General anaesthesia is associated with increased risk of surgical site infection
      after Caesarean delivery compared with neuraxial anaesthesia: a population-based
      study.
AB  - BACKGROUND: This study compared the odds ratio (OR) of surgical site infection
      (SSI) within 30 days after operation with general anaesthesia (GA) or neuraxial
      anaesthesia (NA) in Taiwanese women undergoing Caesarean delivery (CD). METHODS:
      An epidemiologic design was used. The study population was based on the records
      of all deliveries in hospitals or obstetric clinics between January 2002 and
      December 2006 in Taiwan. Anonymized claim data from the Taiwan National Health
      Insurance Research Database (NHIRD) were analysed. Women who received CD were
      identified from the NHIRD by Diagnosis-Related Group codes. The mode of
      anaesthesia was defined by order codes. Multivariate logistic regression was used
      to estimate the OR and associated 95% confidence interval (CI) of post-CD SSIs
      for GA when compared with NA. The outcome was whether a woman had been diagnosed
      as having an SSI during the hospitalization or was re-hospitalized within 30 days
      after CD for the treatment of SSIs using five or 81 International Classification
      of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. RESULTS:
      Among the 303 834 Taiwanese women who underwent CD during the 5 yr observation
      period, the 30 day post-CD SSI rate was 0.3% or 0.9% based on five or 81 ICD-9-CM
      codes. The multivariate-adjusted OR of having post-CD SSIs in the GA group was
      3.73 (95% CI, 3.07-4.53) compared with the NA group (P<0.001) using five ICD-9-CM
      codes for the definition of SSI. CONCLUSIONS: GA for CD was associated with a
      higher risk of SSI when compared with neuraxial anaesthesia.

PMID- 21857017
TI  - Direct effect of morphine on breast cancer cell function in vitro: role of the
      NET1 gene.
AB  - BACKGROUND: Experimental data suggest that postoperative analgesia in general and
      opioids in particular may affect the risk of metastases after primary cancer
      surgery. Perioperative single-gene activation may also spark metastatic disease.
      The NET1 gene promotes migration in adenocarcinoma cells. We investigated opioid
      receptor expression in both breast cancer cell lines and the direct effect of
      morphine and NET-1 on breast cancer cell migration in vitro. METHODS:
      Proliferation and migration of oestrogen receptor-negative MDA-MB-231 and
      oestrogen receptor-positive MCF7 breast cancer cells were studied after
      incubation with morphine 10-100 ng ml(-1) and control. NET1 gene expression was
      determined by polymerase chain reaction. The effect of NET1 on cell migration was
      determined using gene silencing with siRNA and stimulation with lysophosphatidic
      acid (LPA). The effect of morphine on NET1 expression and migration of cells with
      silenced NET1 was investigated. RESULTS: The NET1 gene was expressed in both cell
      lines and stimulated by LPA (2.9-fold in MCF7 and 78-fold in MDA-MB-231). NET1
      expression was decreased by 96% after gene silencing in both cell lines with
      corresponding changes in migration. Despite the lack of opioid receptor
      expression, morphine increased the expression of NET1 (by 94% in MCF7 and by 263%
      in MDA-MB-231 cells). Morphine also increased migration by 17-27% and 7-53% in
      MCF7 and MDA-MB-231, respectively. Silencing the NET1 gene reversed the effect of
      morphine on migration. CONCLUSIONS: The NET1 gene, but not opioid receptors, is
      expressed in breast adenocarcinoma cells and may facilitate their migration.
      Morphine increased both expression of NET1 and cell migration but not when NET1
      was silenced, implying that NET1 contributes to mediating the direct effect of
      morphine on breast cancer cell migration.

PMID- 21857018
TI  - Can blood pressure in the first trimester predict the development of gestational
      hypertensive disorders?

PMID- 21857019
TI  - The endocardial binary appearance ('binary sign') is an unreliable marker for
      echocardiographic detection of Fabry disease in patients with left ventricular
      hypertrophy.
AB  - AIMS: The binary sign, a binary appearance of the left ventricular endocardial
      border, was suggested to be an echocardiographic hallmark in diagnosing Fabry
      disease, a hereditary, lysosomal storage disorder. The aim of the present study
      was to examine the reliability of the binary sign as a screening tool to identify
      patients with Fabry disease. METHODS AND RESULTS: In total 309 subjects with an
      interventricular septum (IVS) thickness of >=12 mm were investigated, of which 14
      had a confirmed diagnosis of Fabry disease. Urinary globotriaosylceramide testing
      was used to rule out Fabry disease in the control group. From all patients
      echocardiographic images of the apical four-chamber view were analysed offline by
      a blinded observer. A binary sign was seen in 63 patients (20%), 4 had Fabry
      disease and 59 belonged to the control group. Although the proportion of binary
      signs in patients with Fabry disease was higher (29%) compared with the control
      group (20%) this difference was not statistically significant. The sensitivity
      and specificity were 28% (95% confidence interval (CI): 12-65%) and 80% (95% CI:
      76-85%), respectively. In a logistic regression model adjusted for age, sex and
      presence of Fabry disease, the occurrence of a binary sign was highly dependent
      on the IVS thickness (odds ratio: 1.21; 95% CI: 1.1-1.35; P<0.001). CONCLUSION:
      The endocardial binary appearance is associated with the degree of septal
      hypertrophy but cannot adequately distinguish between patients with Fabry disease
      and patients with other causes of left ventricular hypertrophy.

PMID- 21857020
TI  - Adverse effect of right ventricular pacing prevented by biventricular pacing
      during long-term follow-up: a randomized comparison.
AB  - AIMS: To investigate whether biventricular (BIV) pacing preserves left
      ventricular ejection fraction (LVEF) and reduces LV dyssynchrony when compared
      with standard dual-chamber right ventricular (RV) pacing in consecutive patients
      with high-grade atrioventricular block during 3 years of pacing. METHODS AND
      RESULTS: Fifty patients were randomized to RV pacing or BIV pacing. LVEF was
      measured using three-dimensional echocardiography. Tissue Doppler imaging was
      used to quantify LV dyssynchrony in terms of the standard deviation of the time
      to-peak velocity (Ts-SD). LVEF differed significantly between the two groups
      during 3 years of pacing (ANOVA: P=0.003). LVEF in the RV group decreased from
      59+/-5% at baseline to 53+/-11% (P=0.01), while LVEF remained unchanged in the
      BIV group (57+/-7% at baseline vs. 58+/-10% (P=0.40). After 3 years of follow-up,
      we observed no difference in LV dyssynchrony, LV remodelling or measurements of
      clinical heart failure (N-terminal pro-brain natriuretic peptide, walking test,
      and New York Heart Association functional class) between the two groups. However,
      in the RV group, but not in the BIV group, dyssynchrony increased significantly
      (P=0.005) during follow-up. Furthermore, adverse LV remodelling was observed in
      the RV group with increased systolic volume and thinning of the LV septum.
      CONCLUSION: BIV pacing preserves LVEF and minimizes LV dyssynchrony during long
      term follow-up. Adverse remodelling observed during 3 years of RV pacing was
      prevented by BIV pacing. However, the adverse impact of RV pacing on LV function
      was not reflected in measures of clinical heart failure. CLINICAL TRIAL
      REGISTRATION: www.clinicaltrials.gov (identification number: NCT00228241).

PMID- 21857021
TI  - Platelet-derived growth factor (PDGF) regulates Slingshot phosphatase activity
      via Nox1-dependent auto-dephosphorylation of serine 834 in vascular smooth muscle
      cells.
AB  - Migration of vascular smooth muscle cells (VSMCs) contributes to vascular
      pathology. PDGF induces VSMC migration by a Nox1-based NADPH oxidase mediated
      mechanism. We have previously shown that PDGF-induced migration in VSMCs requires
      Slingshot-1L (SSH1L) phosphatase activity. In the present work, the mechanism of
      SSH1L activation by PDGF is further investigated. We identified a 14-3-3
      consensus binding motif encompassing Ser-834 in SSH1L that is constitutively
      phosphorylated. PDGF induces SSH1L auto-dephosphorylation at Ser-834 in wild type
      (wt), but not in Nox1(-/y) cells. A SSH1L-S834A phospho-deficient mutant has
      significantly lower binding capacity for 14-3-3 when compared with the phospho
      mimetic SSH1L-S834D mutant, and acts as a constitutively active phosphatase,
      lacking of PDGF-mediated regulation. Given that Nox1 produces reactive oxygen
      species, we evaluated their participation in this SSH1L activation mechanism. We
      found that H(2)O(2) activates SSH1L and this is accompanied by SSH1L/14-3-3
      complex disruption and 14-3-3 oxidation in wt, but not in Nox1(-/y) cells.
      Together, these data demonstrate that PDGF activates SSH1L in VSMC by a mechanism
      that involves Nox1-mediated oxidation of 14-3-3 and Ser-834 SSH1L auto
      dephosphorylation.

PMID- 21857022
TI  - Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation
      and endoplasmic reticulum (ER) protein quality control.
AB  - Quality control of endoplasmic reticulum proteins involves the identification and
      engagement of misfolded proteins, dislocation of the misfolded protein across the
      endoplasmic reticulum (ER) membrane, and ubiquitin-mediated targeting to the
      proteasome for degradation. Ancient ubiquitous protein 1 (AUP1) physically
      associates with the mammalian HRD1-SEL1L complex, and AUP1 depletion impairs
      degradation of misfolded ER proteins. One of the functions of AUP1 in ER quality
      control is to recruit the soluble E2 ubiquitin-conjugating enzyme UBE2G2. We
      further show that the CUE domain of AUP1 regulates polyubiquitylation and
      facilitates the interaction of AUP1 with the HRD1 complex and with dislocation
      substrates. AUP1 localizes both to the ER and to lipid droplets. The AUP1
      expression level affects the abundance of cellular lipid droplets and as such
      represents the first protein with lipid droplet regulatory activity to be linked
      to ER quality control. These findings indicate a possible connection between ER
      protein quality control and lipid droplets.

PMID- 21857023
TI  - The Triangle Model for evaluating the effect of health information technology on
      healthcare quality and safety.
AB  - With the proliferation of relatively mature health information technology (IT)
      systems with large numbers of users, it becomes increasingly important to
      evaluate the effect of these systems on the quality and safety of healthcare.
      Previous research on the effectiveness of health IT has had mixed results, which
      may be in part attributable to the evaluation frameworks used. The authors
      propose a model for evaluation, the Triangle Model, developed for designing
      studies of quality and safety outcomes of health IT. This model identifies
      structure-level predictors, including characteristics of: (1) the technology
      itself; (2) the provider using the technology; (3) the organizational setting;
      and (4) the patient population. In addition, the model outlines process
      predictors, including (1) usage of the technology, (2) organizational support for
      and customization of the technology, and (3) organizational policies and
      procedures about quality and safety. The Triangle Model specifies the variables
      to be measured, but is flexible enough to accommodate both qualitative and
      quantitative approaches to capturing them. The authors illustrate this model,
      which integrates perspectives from both health services research and biomedical
      informatics, with examples from evaluations of electronic prescribing, but it is
      also applicable to a variety of types of health IT systems.

PMID- 21857025
TI  - Reducing stress burden and objective burden in spousal caregivers through
      implementation of Powerful Tools for Caregivers.

PMID- 21857024
TI  - The impact of computer self-efficacy, computer anxiety, and perceived usability
      and acceptability on the efficacy of a decision support tool for colorectal
      cancer screening.
AB  - OBJECTIVE: This study investigated the efficacy of an internet-based personalized
      decision support (PDS) tool designed to aid in the decision to screen for
      colorectal cancer (CRC) using a fecal occult blood test. We tested whether the
      efficacy of the tool in influencing attitudes to screening was mediated by
      perceived usability and acceptability, and considered the role of computer self
      efficacy and computer anxiety in these relationships. METHODS: Eighty-one
      participants aged 50-76 years worked through the on-line PDS tool and completed
      questionnaires on computer self-efficacy, computer anxiety, attitudes to and
      beliefs about CRC screening before and after exposure to the PDS, and perceived
      usability and acceptability of the tool. RESULTS: Repeated measures ANOVA found
      that PDS exposure led to a significant increase in knowledge about CRC and
      screening, and more positive attitudes to CRC screening as measured by factors
      from the Preventive Health Model. Perceived usability and acceptability of the
      PDS mediated changes in attitudes toward CRC screening (but not CRC knowledge),
      and computer self-efficacy and computer anxiety were significant predictors of
      individuals' perceptions of the tool. CONCLUSION: Interventions designed to
      decrease computer anxiety, such as computer courses and internet training, may
      improve the acceptability of new health information technologies including
      internet-based decision support tools, increasing their impact on behavior
      change.

PMID- 21857026
TI  - An ultrasonographic study of metatarsophalangeal joint pain: synovitis,
      structural pathology and their relationship to symptoms and function.
AB  - BACKGROUND: Pain in the first metatarsophalangeal joint (MTPJ) is common, though
      the link between pathology and symptoms is poorly understood. OBJECTIVES: To
      examine the relationship between pain, function and ultrasound (US)-detected
      pathology in the first MTPJ. METHODS: 33 subjects with first MTPJ pain and 20
      asymptomatic controls completed questionnaires about pain and function, then
      underwent clinical examination, US examination and objective assessment of
      function using a motion tracking system. RESULTS: Low-level grey scale synovitis
      and osteophytes were common in patients and controls. Osteophytes were more
      prevalent in symptomatic first MTPJ [24/33 (73%) vs. 7/20 (35%), p=0.007], and
      greater osteophyte numbers were weakly associated with higher levels of pain
      [increase in pain VAS per osteophyte (95% CI)=13.78mm (0.12mm-27.43mm), p=0.048].
      A power Doppler (PD) signal was present in a fifth of painful first MTPJs and
      absent in controls. A PD signal was associated with osteophytes and joint space
      narrowing but was not independently related to target joint pain. For all first
      MTPJs, osteophytes and the presence of a PD signal was associated with worse
      patient-reported function. US features did not predict objective function.
      CONCLUSION: Osteophytes, representing subchondral bone remodelling, were
      associated with the presence of first MTPJ pain and, together with more severe
      (PD) synovitis, also contributed to poorer function. Detailed imaging of bone may
      provide more information on peripheral pain associations.

PMID- 21857027
TI  - A discrete event modelling framework for simulation of long-term outcomes of
      sequential treatment strategies for ankylosing spondylitis.
AB  - OBJECTIVE: To develop a modelling framework which can simulate long-term quality
      of life, societal costs and cost-effectiveness as affected by sequential drug
      treatment strategies for ankylosing spondylitis (AS). METHODS: Discrete event
      simulation paradigm was selected for model development. Drug efficacy was
      modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis
      Functional Index (BASFI)), which were linked to costs and health utility using
      statistical models fitted based on an observational AS cohort. Published clinical
      data were used to estimate drug efficacy and time to events. Two strategies were
      compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1)
      and (2) same as strategy 1 plus two tumour necrosis factor alpha inhibitors
      (strategy 2). 13,000 patients were followed up individually until death. For
      probability sensitivity analysis, Monte Carlo simulations were performed with
      1000 sets of parameters sampled from the appropriate probability distributions.
      RESULTS: The models successfully generated valid data on treatments, BASDAI,
      BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with
      intervals of 1-3 months during the simulation length of 70 years. Incremental
      cost per QALY gained in strategy 2 compared with strategy 1 was ?35,186. At a
      willingness-to-pay threshold of ?80,000, it was 99.9% certain that strategy 2 was
      cost-effective. CONCLUSIONS: The modelling framework provides great flexibility
      to implement complex algorithms representing treatment selection, disease
      progression and changes in costs and utilities over time of patients with AS.
      Results obtained from the simulation are plausible.

PMID- 21857028
TI  - The Standard Days Method: an addition to the arsenal of family planning method
      choice in Ethiopia.
AB  - BACKGROUND AND METHODOLOGY: The Standard Days Method (r) (SDM) is a fertility
      awareness-based method of family planning that helps users to identify the
      fertile days of the reproductive cycle (Days 8-19). To prevent pregnancy users
      avoid unprotected sexual intercourse during these days. A cross-sectional
      community-based study was conducted from December 2007 to June 2008 in four
      operational areas of Pathfinder International Ethiopia. A total of 184 SDM users
      were included in the study. Quantitative and qualitative methods of data
      collection were used. The aim of the study was to examine the experience of
      introducing the SDM at community level in Ethiopia. RESULTS: Of the 184
      participants, 80.4% were still using the SDM at the time of the survey, with 35%
      having used it for between 6 and 12 months, while 42% had used it for more than a
      year. The majority (83%) knew that a woman is most likely to conceive halfway
      through her menstrual cycle, and nearly 91% correctly said that the SDM does not
      confer protection from sexually transmitted infections/AIDS. A substantial
      majority (75%) had correctly identified what each colour-coded bead represents in
      the CycleBeads (r), and an aggregate of 90.5% of women practised all the elements
      of correct use. DISCUSSION AND CONCLUSIONS: This study demonstrates the
      importance of the SDM in increasing the availability and accessibility of family
      planning, and the potential to improve family planning method choice and method
      mix by expanding use of the SDM.

PMID- 21857029
TI  - Continued use of the Standard Days Method.
AB  - OBJECTIVE: To examine the long-term effectiveness and continuation of the
      Standard Days Method (SDM)(r), a fertility awareness-based method of family
      planning that identifies Days 8-19 (inclusive) of the cycle as the fertile
      window. On these days users avoid unprotected sexual intercourse to prevent
      pregnancy. The method works best for women with cycles that are usually in the
      range of 26-32 days, which is an important reason for method discontinuation in
      the first year of use. The authors determine if this continues to be an issue in
      the second and third years of method use. METHODS: Participants in an earlier
      efficacy study (478 women in three countries) and method introduction studies
      (1181 women in four countries) were followed for 2 years beyond the original 1
      year study period, to determine their continued use of the method, intended and
      unintended pregnancies, and reasons for discontinuation. Life-tables were used to
      approximate typical use pregnancy rates. RESULTS: The method continues to be
      effective in the second and third years of use, and compares favourably to other
      user-directed family planning methods. Women with no more than two cycles outside
      the 26-32-day range within a year are likely to continue having cycles within
      this range. CONCLUSIONS: Women who complete the first year of SDM use are likely
      to continue to be able to use the method successfully and effectively. The method
      presents a viable longer-term option for women who prefer this approach to family
      planning.

PMID- 21857031
TI  - Neural basis of music knowledge: evidence from the dementias.
AB  - The study of patients with semantic dementia has revealed important insights into
      the cognitive and neural architecture of semantic memory. Patients with semantic
      dementia are known to have difficulty understanding the meanings of environmental
      sounds from an early stage but little is known about their knowledge for famous
      tunes, which might be preserved in some cases. Patients with semantic dementia (n
      = 13), Alzheimer's disease (n = 14) as well as matched healthy control
      participants (n = 20) underwent a battery of tests designed to assess knowledge
      of famous tunes, environmental sounds and famous faces, as well as volumetric
      magnetic resonance imaging. As a group, patients with semantic dementia were
      profoundly impaired in the recognition of everyday environmental sounds and
      famous tunes with consistent performance across testing modalities, which is
      suggestive of a central semantic deficit. A few notable individuals (n = 3) with
      semantic dementia demonstrated clear preservation of knowledge of known melodies
      and famous people. Defects in auditory semantics were mild in patients with
      Alzheimer's disease. Voxel-based morphometry of magnetic resonance brain images
      showed that the recognition of famous tunes correlated with the degree of right
      anterior temporal lobe atrophy, particularly in the temporal pole. This area was
      segregated from the region found to be involved in the recognition of everyday
      sounds but overlapped considerably with the area that was correlated with the
      recognition of famous faces. The three patients with semantic dementia with
      sparing of musical knowledge had significantly less atrophy of the right temporal
      pole in comparison to the other patients in the semantic dementia group. These
      findings highlight the role of the right temporal pole in the processing of known
      tunes and faces. Overlap in this region might reflect that having a unique
      identity is a quality that is common to both melodies and people.

PMID- 21857030
TI  - Quantitative phospho-proteomics to investigate the polo-like kinase 1-dependent
      phospho-proteome.
AB  - Polo-like kinase 1 (PLK1) is a key regulator of mitotic progression and cell
      division, and small molecule inhibitors of PLK1 are undergoing clinical trials to
      evaluate their utility in cancer therapy. Despite this importance, current
      knowledge about the identity of PLK1 substrates is limited. Here we present the
      results of a proteome-wide analysis of PLK1-regulated phosphorylation sites in
      mitotic human cells. We compared phosphorylation sites in HeLa cells that were or
      were not treated with the PLK1-inhibitor BI 4834, by labeling peptides via methyl
      esterification, fractionation of peptides by strong cation exchange
      chromatography, and phosphopeptide enrichment via immobilized metal affinity
      chromatography. Analysis by quantitative mass spectrometry identified 4070 unique
      mitotic phosphorylation sites on 2069 proteins. Of these, 401 proteins contained
      one or multiple phosphorylation sites whose abundance was decreased by PLK1
      inhibition. These include proteins implicated in PLK1-regulated processes such as
      DNA damage, mitotic spindle formation, spindle assembly checkpoint signaling, and
      chromosome segregation, but also numerous proteins that were not suspected to be
      regulated by PLK1. Analysis of amino acid sequence motifs among phosphorylation
      sites down-regulated under PLK1 inhibition in this data set identified two
      potential novel variants of the PLK1 consensus motif.

PMID- 21857032
TI  - Two-year outcomes of transforaminal lumbar interbody fusion.
AB  - PURPOSE: To evaluate the outcomes, fusion rates, complications, and adjacent
      segment degeneration associated with transforaminal lumbar interbody fusion
      (TLIF). METHODS: 32 men and 80 women aged 15 to 85 (mean, 57) years underwent 141
      fusions (84 one-level, 27 2-level, and one 3-level) and were followed up for 24
      to 76 (mean, 33) months. 92% of the patients had degenerative lumbar disease, 15
      of whom had had previous lumbar surgery. Radiographic and clinical outcomes were
      assessed at 2 years. The short-form 36 (SF-36) health survey, visual analogue
      scale (VAS) for pain, and the modified North American Spine Society (NASS) Low
      Back Pain Outcome Instrument were used. RESULTS: Of the 141 levels fused, 110
      (78%) were fused with remodelling and trabeculae (grade I), and 31 (22%) had
      intact grafts but were not fully incorporated (grade II). No patient had
      pseudoarthroses (grade III or IV). For one-level fusions, poorer radiological
      fusion grades correlated with higher VAS scores for pain (p<0.01). All components
      of the SF-36, the VAS scores for pain, and the NASS scores improved significantly
      after TLIF (p<0.01), except for general health in the SF-36 (p=0.59). Improvement
      from postoperative 6 months to 2 years was not significant, except for physical
      function (p<0.01) and role function (physical) [p=0.01] in the SF-36. Two years
      after TLIF, 50% of the patients reported returning to full function, whereas 72%
      were satisfied. 26 (23%) of the patients had adjacent segment degeneration, but
      only 4 of them were symptomatic. CONCLUSION: TLIF is a safe and effective
      treatment for degenerative lumbar diseases.

PMID- 21857033
TI  - Factors predicting progression in early degenerative lumbar scoliosis.
AB  - PURPOSE: To review early radiographs of patients with de novo degenerative lumbar
      scoliosis to determine factors predicting early scoliosis progression. METHODS:
      Standing anteroposterior and lateral radiographs of 7 men and 20 women aged 48 to
      83 (mean, 63) years with Cobb angles between >5o and <20o were reviewed. They
      were followed up for a mean of 12 (range, 10-18) years. Radiographic variables
      measured included (1) the Cobb angle, (2) the grade of rotation of the apical
      lumbar vertebra, (3) the presence of a lateral vertebral translation of >=3 mm,
      (4) the degree of osteoporosis, and (5) the Harrington factor (the degree of
      scoliosis divided by the number of vertebrae involved). RESULTS: During the
      follow-up period, the mean Cobb angle increased 5.3o from 10.1o to 15.4o,
      representing an increase of 0.4o per year. In initial radiographs, the apical
      vertebral rotation was rated as grade 0 in 3 patients, grade 1 in 19, grade 2 in
      4, and grade 3 in one. A lateral vertebral translation of >=3 mm was noted in 9
      patients. The degree of osteoporosis was rated as grade 0 in 9 patients, grade 1
      in 11, grade 2 in 5, and grade 3 in 2. The mean Harrington factor was 2.4. In the
      multiple regression analysis, only the grade of apical vertebral rotation was
      significantly correlated with scoliosis progression (regression
      coefficient=0.502, p=0.009). CONCLUSION: Apical vertebral rotation may help
      predict the scoliosis progression and determine the timing of surgical
      intervention in patients with early degenerative lumbar scoliosis.

PMID- 21857034
TI  - Sensitivity, specificity and accuracy of magnetic resonance imaging for
      differentiating vertebral compression fractures caused by malignancy,
      osteoporosis, and infections.
AB  - PURPOSE: To evaluate the sensitivity, specificity and accuracy of various
      magnetic resonance imaging (MRI) features in differentiating vertebral
      compression fractures caused by malignancy, osteoporosis, and infections.
      METHODS: 35 men and 45 women aged 40 to 78 (mean, 59) years underwent MRI to
      assess the underlying pathology of already diagnosed vertebral compression
      fractures (n=152). The interval from presentation to imaging ranged from 7 to 95
      (mean, 62) days. MRI features of each vertebral compression fracture were
      assessed. The sensitivity, specificity, and accuracy for each of the MRI features
      were calculated. Association between each MRI feature and various underlying
      pathologies (malignancy, osteoporosis, and infections) of vertebral compression
      fractures was evaluated. RESULTS: Regarding these 80 patients, the MRI diagnosis
      was correct in 78 and inconclusive in 2 with malignancy. MRI features suggestive
      of malignant fractures were a convex posterior border of the vertebral body,
      pedicle involvement, posterior neural element involvement, an epidural mass, a
      paraspinal mass, and other spinal metastases. MRI features suggestive of
      osteoporotic fractures were retropulsion, low signal intensity band, spared
      normal marrow signal intensity, and the fluid sign. MRI features suggestive of
      infective fractures were contiguous vertebral involvement, end plate disruption,
      disc involvement, and paraspinal and epidural abscesses. CONCLUSION: Combination
      of several MRI features can provide clues to differentiate between malignant,
      osteoporotic, and infective vertebral compression fractures.

PMID- 21857035
TI  - Collagen membranes for host-graft integration: an animal study.
AB  - PURPOSE: To evaluate the biocompatibility of collagen membranes for host-graft
      integration. METHODS: 18 Achilles tendons in 9 rats were used. Five tendons were
      controls and repaired with prolene 3-0 sutures only. The remaining 13 tendons
      were cases, and a 10-mm section was excised. A 15x5 mm bovine pericardial
      collagen membrane (Tutomesh; Tutogen Medical, Germany) was laid circumferentially
      around the tendon and secured with prolene 3-0 sutures. Tendons were harvested
      after 4 and 6 weeks. Only the repair interfaces (i.e. cut ends and immediate
      surrounding tissue) were evaluated. Integration of the membranes to the tendons
      was evaluated using a semi-quantitative wound maturation scale (1-4) based on the
      presence of inflammatory cells, vascularisation, fibroblasts, and the amount and
      alignment of collagen fibrils. The presence of fibroblasts and vascularisation
      were positive parameters, whereas inflammatory cell ratios were regarded as
      negative parameters. Immunohistochemical study was also performed. RESULTS: There
      was no host-graft reaction or wound complication (infection, abscess or seroma).
      Histological and immunohistochemical assessment confirmed re-approximation of the
      cut tendon ends and incorporation of the membrane onto the tendon as early as
      week 4. At week 4, the mean maturation scale scores were 2.7 for controls and 3.3
      for cases (p=0.11). At week 6, the corresponding values were 3.8 and 3.0
      (p=0.004). A reparative process involving formation of blood vessels and invasion
      by fibroblasts was noted in both control and case tendons. In controls, T- and B
      lymphocytes were present. In cases, inflammatory cells were noted at the junction
      of the host and membrane without invasion of the graft material. There was no
      lymphocytic infiltration on the graft. The foreign body reaction was localised
      and minimal. CONCLUSION: The collagen membrane achieved favourable host-graft
      integration as early as week 4, with a minimal foreign body reaction.

PMID- 21857036
TI  - Collagen membranes for host-implant integration: a pilot clinical study.
AB  - PURPOSE: To evaluate host-implant integration with collagen membranes in 14
      patients who underwent limb salvage surgery for musculoskeletal oncological
      disease. METHODS: 8 females and 6 males aged 10 to 69 (mean, 30) years underwent
      limb savage surgery with collagen membranes (Tutomesh; Tutogen Medical, Germany)
      for osteosarcoma (n=7), chondrosarcoma (n=3), giant cell tumour (n=1), malignant
      fibrous histiocytoma (n=1), arteriovenous malformation (n=1), and pigmented
      villonodular synovitis (n=1). The procedures performed were proximal humeral
      resection (n=3), partial scapulectomy (n=1), proximal femoral resection (n=2),
      total femoral resection (n=2), proximal tibial resection (n=3), and wide
      resection of soft tissues of the knee (n=3). In addition, 10 patients underwent
      endoprosthesis reconstruction. Reconstruction of musculoskeletal defects was
      classified into type I (intercalary, n=2), type II (joint, n=4), and type III
      (both, n=8). Graft incorporation and local recurrence were monitored. Clinical
      outcome measures entailed the Short Form-36, Toronto Extremity Salvage Score
      (TESS), and Musculoskeletal Tumor Society Score (MSTS). RESULTS: Two patients
      with proximal tibial resection and one with total femoral resection had wound
      healing problems. No patient had any infection or any foreign body reaction
      necessitating implant removal. Eight patients with type II or III reconstruction
      were followed up for a mean of 11 (range, 1-23) months. Their scores in the Short
      Form-36, TESS, and MSTS were similar to those who had undergone reconstructions
      without the membrane, with the exception of type II reconstructions for which the
      membrane conferred good results. CONCLUSION: The Tutomesh membrane facilitated
      host-implant integration and provided a feasible anatomic reconstruction for
      ligaments in the shoulder, knee, and hip.

PMID- 21857037
TI  - Medium-term outcome of titanium uncemented stems in revision total hip
      arthroplasty.
AB  - PURPOSE: To assess the medium-term outcome of titanium uncemented modular tapered
      stems in revision total hip arthroplasty (THA). METHODS: A questionnaire was
      mailed to 421 patients who underwent revision THA using a titanium uncemented
      modular tapered stem. 66 of whom underwent re-revision THA. The questionnaire was
      composed to reveal the Charnley classification, the modified 12-item Oxford hip
      score, and the Devane patient activity level. RESULTS: 323 (77%) of the patients
      responded. The mean follow-up time was 6.6 years. 12 patients underwent bilateral
      revision THA. The mean Oxford hip score was 35.7, compared to 35.8 for all
      component revision at postoperative month 6 in the New Zealand Joint Registry.
      The median Oxford hip scores for the subgroups of the stem-only revision (n=92),
      all-component revision (n=215), and re-revision (n=16) were 38, 39.9, and 30,
      respectively. The difference was significant between all-component revision and
      re-revision (adjusted p=0.003), and between stem-only revision and re-revision
      (adjusted p=0.037). Regarding patient distribution according to the Charnley
      class and the Devane patient activity level, the difference was significant
      between the mean Oxford hip scores of Charnley classes B and C (adjusted
      p=0.017), and between the Devane patient activity levels of Charnley classes A
      and C (adjusted p=0.043). CONCLUSION: The medium-term outcome of revision THA
      using a titanium uncemented modular tapered stem was comparable to that reported
      for other stems.

PMID- 21857038
TI  - Cementless total hip arthroplasty using titanium, plasma-sprayed implants: a
      study with 10 to 15 years of follow-up.
AB  - PURPOSE: To evaluate long-term outcomes of total hip arthroplasty (THA) using the
      Perfecta cementless system. METHODS: 73 men and 76 women aged 65 to 88 (mean, 71)
      years underwent 168 THAs using the Perfecta cementless system and were followed
      up for a mean of 13 (10 to 15) years. 19 patients had bilateral THA. The
      diagnoses were idiopathic osteoarthritis (n=121), osteonecrosis of the femoral
      head (n=25), rheumatoid arthritis (n=14), and post-traumatic osteoarthritis
      (n=8). Patients were evaluated clinically and radiographically before and after
      THA. RESULTS: The mean Harris hip score improved from 40 to 84 (p<0.001); the
      score was excellent or good in 130 hips, fair in 17, and poor in 21. The mean
      Merle D'Aubigne score improved from 4 to 10 (p<0.001); the score was excellent or
      good in 138 hips, fair in 9, and poor in 21. Poor results were due to aseptic
      revision of the cup (n=16) or stem (n=3) or deep infection (n=2). Thigh pain that
      limited activities of daily living was noted in 3 hips. 142 patients could walk
      without a limp, 5 had a slight limp, and 3 had a moderate limp and used a cane.
      The mean Short Form-12 score for the physical function was 49 and for the mental
      health was 56; the mean Western Ontario and McMaster Universities Osteoarthritis
      Index was 39; the mean visual analogue scale score for satisfaction was 8. Two
      patients developed deep infection at postoperative months 8 and 50 and were
      treated with 2-staged revision. Five patients had hip dislocation within 2
      months; 3 of whom endured recurrent dislocation and underwent revision surgery;
      they had acetabular malposition with excessive anteversion despite a correct
      acetabular angle. 13 other cups were revised because of loosening or extensive
      osteolysis (n=10) and polyethylene wear (n=3) after a mean interval of 6 (range,
      4-10) years. Three stems were revised because of aseptic loosening after a mean
      interval of 7 (range, 6-9) years. The survivorship at 14 years was 99% for stems
      and 91% for cups. CONCLUSION: The long-term outcome of the Perfecta cementless
      stem was good; most major complications occurred in the cup.

PMID- 21857039
TI  - Long-term outcome of total hip replacement in patients with or without femoral
      head contamination.
AB  - PURPOSE: To compare long-term outcomes of total hip replacement (THR) in patients
      with or without contamination of the femoral head. METHODS: After a mean period
      of 12 (range, 8-17) years, 104 female and 71 male THR patients aged 47 to 96
      (mean, 77) years were reassessed via a self-administered questionnaire, and 25
      other THR patients were reassessed by review of case notes. The questionnaires
      comprised the 12-item Oxford hip score and the European Quality Of Life
      (EuroQOL). 87 and 88 patients had positive and negative cultures in the donated
      femoral heads, respectively. The 2 groups were compared with respect to the
      Oxford hip score, the EuroQOL, and rates of complication and revision surgery.
      RESULTS: Long-term outcomes of THR patients with or without femoral head
      contamination were not significantly different. Respectively, the mean Oxford hip
      scores were 36 and 39 (p=0.4); 16 and 14 patients had the maximum score of 48; 2
      and 3 patients scored <10 (mostly owing to aseptic loosening). The respective
      mean visual analogue scale score of the EuroQOL were 65 and 73 (p=0.07); only the
      dimension of self care was significantly different between groups (p=0.04).
      Respectively, 14 and 12 patients had complications (16% vs. 15%, chi2=0.05,
      p=0.8), whereas 11 and 5 patients had revision surgery (13% vs. 6%, chi2=2.2,
      p>0.1). CONCLUSION: Microbiological screening of donated femoral heads plays no
      role in predicting long-term failure of THR in the donors.

PMID- 21857040
TI  - Hemi-resurfacing versus total resurfacing for osteonecrosis of the femoral head.
AB  - PURPOSE: To compare mid-term outcomes of hemi-resurfacing arthroplasty (HRA) and
      total resurfacing arthroplasty (TRA). METHODS: Seven men and 5 women (16 hips)
      aged 33 to 72 (mean, 50) years underwent HRA, whereas 7 men and 3 women (16 hips)
      aged 23 to 52 (mean, 40) years underwent metal-on-metal TRA; all were for
      osteonecrosis of the femoral head. In the HRA and TRA groups respectively, 10 and
      8 hips were steroid-induced, whereas 6 and 8 hips were related to alcohol abuse.
      Surgery for 12 and 4 hips entailed the posterolateral approach, whereas 4 and 12
      hips entailed the Hardinge approach. Usually, HRA was performed for early stages
      of the disease, and TRA for more advanced stages. 12 and 6 hips were classified
      as JOA stages 1 to 3A, whereas 4 and 10 hips as stages 3B to 4. All the hips were
      JOA types C1 or C2. RESULTS: In the HRA and TRA groups respectively, the mean
      follow-up period were 6.5 and 5.5 years. The mean total JOA hip scores were 57
      and 54 preoperatively, 93 and 97 at one year, and 84 and 96 at the final follow
      up (p<0.01). The higher score in the TRA patients was mainly attributed to
      improvement in the pain score. In the HRA group, 12 hips developed groin pain or
      groin discomfort while walking, though only 4 of them showed apparent joint-space
      narrowing. Five patients underwent revision surgeries (conversion to total hip
      arthroplasty) owing to a femoral neck fracture, acetabular protrusio,
      osteoarthritic change, and severe groin pain. Patients having TRA had no revision
      surgery and did not complain of groin pain. Implants in both groups were
      radiographically stable. CONCLUSION: TRA were superior to HRA in terms of pain
      relief and implant survival, even though the former procedure was used for more
      advanced cases.

PMID- 21857041
TI  - Autologous blood reinfusion in patients undergoing bilateral total hip
      arthroplasty.
AB  - PURPOSE: To compare the rate and unit of allogeneic blood transfusion in one
      stage bilateral total hip arthroplasty (THA) in patients with and without
      autologous blood reinfusion. METHODS: Records of a consecutive series of 43 men
      and 33 women aged 25 to 83 (mean, 55) years who underwent one-stage sequential
      bilateral THA by a single surgeon were reviewed. Their risks of cardiopulmonary
      complications were minimal. At least 4 weeks prior to surgery, 38 of the patients
      donated 2 units of autologous blood in 2 stages (one to 2 weeks apart). The
      remaining 38 patients did not donate blood owing to personal preferences or
      logistical reasons. All pre-donated autologous blood was transfused back to the
      patients in the recovery room. Estimated blood loss volume, blood salvaged
      volume, and complications were recorded, as were pre- and post-operative
      haemoglobin levels. The 2 groups were compared with respect to the rate and unit
      of allogeneic blood transfusion. RESULTS: The mean estimated blood loss was 939
      (SD, 448; range, 200-2500) ml. The mean volume of blood salvaged was 302 (SD,
      196; range, 0-850) ml, representing a collection rate of 32%. In patients with
      and without autologous blood reinfusion, 16 (42%) and 33 (87%) patients received
      allogeneic blood transfusion of 0.9 and 2.4 units, respectively (p<0.0001). Four
      patients developed major cardiopulmonary complications. None had deep venous
      thrombosis or pulmonary embolism. No complications resulted from blood
      transfusion. The 2 groups were not significantly different in complication rate
      (13% vs. 18%, p=0.54) and discharge haemoglobin levels. CONCLUSION: Autologous
      blood reinfusion was effective in reducing the rate and unit of allogeneic blood
      transfusion in patients undergoing one-stage bilateral THA.

PMID- 21857042
TI  - Minimally invasive plate osteosynthesis using a locking compression plate for
      distal femoral fractures.
AB  - PURPOSE: To evaluate treatment outcomes of minimally invasive plate
      osteosynthesis (MIPO) for distal femoral fractures in 31 patients. METHODS: 22
      male and 9 female consecutive patients aged 21 to 65 (mean, 42) years underwent
      minimally invasive plate osteosynthesis using a locking compression plate (LCP)
      for distal femoral fractures. The causes of injury were vehicular accidents
      (n=24), falls (n=6), and assault (n=1). According to the AO classification, the
      fractures were classified as types A1 (n=10), A2 (n=7), and A3 (n=14). Most
      fractures were closed; 3 were Gustilo type-II fractures. Clinical and functional
      outcomes were assessed using the Knee Society Scores. RESULTS: The mean operating
      time was 70 (range, 60-100) minutes. The mean length of hospital stay was 9 (6
      14) days. The mean time to union was 3.7 (range, 2.8-4.6) months. The mean follow
      up period was 18 (14-26) months. At the one-year follow-up, 29 of the patients
      had good or excellent outcomes. No patient had angular or rotational deformity of
      >10o. One osteoporotic woman with a type-A1 fracture had implant failure at 10
      weeks and underwent revision surgery. Another patient with a type-A1 fracture had
      persistent pain on the lateral aspect of the distal thigh and underwent implant
      removal at 22 months. No patient developed deep infection, malunion or nonunion.
      CONCLUSION: MIPO using a LCP achieves favourable biological fixation for distal
      femoral fractures with few complications. Bone grafting is not needed even in
      cases of metaphyseal comminution. Proper patient selection and preoperative
      planning are essential to prevent complications.

PMID- 21857043
TI  - Internal fixation and strut allograft augmentation for periprosthetic humeral
      fractures.
AB  - PURPOSE: To report 6 patients with periprosthetic humeral fractures treated with
      open reduction and internal fixation with plate and strut allograft augmentation.
      METHODS: 6 women aged 69 to 79 (mean, 73) years underwent open reduction and
      internal fixation with plate and strut allograft augmentation for periprosthetic
      humeral fractures (type C) after a fall. They had undergone reverse shoulder
      arthroplasty for rotator cuff arthropathy. The mean interval between the initial
      arthroplasty and the fracture was 17 (range, 11-21) months. RESULTS: The mean
      follow-up period was 14 (range, 12-16) months. The mean time to union was 5.4
      (range, 4-6) months. All fractures united without complications. The mean
      Constant score at the last follow-up was 64 (range, 56-80). The range of shoulder
      movement and patient satisfaction were restored to pre-fracture status in all
      patients, except for one who had more pain in the lateral area of the arm
      (probably because of soft-tissue irritation by the plate and wires). Three
      patients had evidence of graft-to-host union and 3 others had graft resorption.
      CONCLUSION: Internal fixation with plate, cable wires and strut allogaft
      augmentation achieves satisfactory results for periprosthetic humeral fractures.

PMID- 21857044
TI  - Hemiarthroplasty for comminuted proximal humeral fractures.
AB  - PURPOSE: To evaluate early functional outcomes of hemiarthroplasty for 3- or 4
      part proximal humeral fractures. METHODS: 16 men and 11 women aged 27 to 83
      (mean, 56) years underwent hemiarthroplasty for comminuted 3-part (n=13) or 4
      part (n=14) proximal humeral fractures. All the patients reported normal shoulder
      function prior to injury. The range of shoulder motion and muscle power were
      evaluated, as were subjective pain and satisfaction (using the UCLA scoring
      system). RESULTS: At the final follow-up, the mean maximum abduction was 111o
      (SD, 47o; range, 30o-180o), and the mean maximum forward flexion was 143o (SD,
      41o; range, 45o-180o). All patients had radiographic union of the tuberosities.
      The mean UCLA score was 28; 21 patients attained good-to-excellent scores (>=27),
      whereas 6 attained lower (fair-to-poor) scores. The mean UCLA score was higher in
      patients aged <60 (n=13) than those who were older (n=14) [30 vs. 26, p=0.008]
      and in patients operated after 7 days (n=6) than those operated before 7 days
      (n=21) [32 vs. 27, p=0.02], but did not differ significantly in terms of gender
      and fracture type and side. Patient age and gender, fracture type, and injury-to
      surgery interval did not have a significant impact on maximum forward flexion and
      abduction. CONCLUSION: Early functional outcomes of hemiarthroplasty for
      comminuted proximal humeral fractures is good in medically fit and cooperative
      patients.

PMID- 21857045
TI  - Screening for developmental dysplasia of the hip in Hong Kong.
AB  - PURPOSE: To review records of children referred to our hospital for developmental
      dysplasia of the hip (DDH) and evaluate the effectiveness of hip screening in
      Hong Kong. METHODS: Records of children suspected of DDH and referred to our
      hospital between 1 January 2005 and 31 March 2010 were reviewed. The diagnosis
      was based on static and dynamic ultrasonography of the hips and/or radiographic
      features of hip subluxation, dislocation, and pelvic dysplasia. The age of the
      children at presentation was recorded. Late diagnoses were those presenting after
      the age of 6 months. Late presentations were those presenting after the walking
      age. RESULTS: Of 213 referred children, 33 were diagnosed to have DDH. Their mean
      age at presentation was 90.8 (range, 9-559) days. The female-to-male ratio was
      2.9:1, and the mean follow-up duration was 25.1 (range, 4.2-50.3) months. 30 of
      the DDH infants were diagnosed before the age of 6 months, one at 8 months, and 2
      were late presenters. Hence, the failure rate of the hip screening was 0.09 per
      1000 live births. The remaining 180 were confirmed to be normal and followed up
      until the walking age. The point prevalence of DDH on Hong Kong Island was
      0.87/1000 live births. CONCLUSION: In light of the low point prevalence of DDH in
      Hong Kong born children, the protocol of universal clinical assessment and
      selective ultrasonographic screening of suspected cases is justified.

PMID- 21857046
TI  - Ilizarov technique of lengthening and then nailing for height increase.
AB  - PURPOSE: To investigate the risks and types of complications associated with the
      Ilizarov technique of lengthening and then nailing in persons of normal height.
      METHODS: Records of 26 men and 6 women aged 21 to 47 (mean, 27) years with body
      height of 160 to 176 (mean, 170) cm who underwent tibial and fibular lengthening
      and then intramedullary nailing were reviewed. They were skeletally mature
      healthy persons, with no systemic/local bone disease, deformity or limb length
      discrepancy. Pain was assessed using the visual analogue scale (VAS). Patient
      satisfaction in terms of the treatment outcomes and expectations was also
      assessed. Complications encountered during or after treatment were recorded.
      RESULTS: The mean lengthening achieved was 7.6 (range, 3.5-12) cm or 26% (range,
      10-40%) of the original length. The mean duration of external fixation was 96
      (range, 45-135) days. The mean follow-up duration after intramedullary nailing
      was 38.7 (range, 24-93) months. The mean VAS pain score was 9.3 at week 1, 6.6 at
      week 4, and 5.7 at week 8. After intramedullary nailing, the mean VAS pain score
      was 2.6 at week 4, 0.9 at month 6, and 0.3 at year 1. 91% of the patients were
      satisfied with the outcome at week 6; 81% after intramedullary nailing, and 94%
      at the one-year follow-up. Four patients had revision operations: one for pin
      exchange owing to pin bending after a fall, one for adjusting external rotation
      of the tibia after nailing, one for bone grafting for delayed union, and one for
      drainage of a haematoma just after nailing. CONCLUSION: Most complications
      related to patient discomfort and psychological stress, which were important
      issues in this type of patients.

PMID- 21857047
TI  - Radial neck fractures in children.
AB  - PURPOSE: To review records of 108 children with radial neck fractures and develop
      an algorithm for treatment. METHODS: Records of 50 girls and 58 boys aged 2 to 14
      (mean, 8.7) years with radial neck fractures were reviewed. The most common
      injury mechanism was tripping and falling on an outstretched hand while running
      (n=44), followed by falling from monkey bars (n=11). Fractures were classified
      into grade 1 (n=25), grade 2 (n=60), grade 3 (n=16), grade 4a (n=6), and grade 4b
      (n=1). 21 patients had associated fractures involving the olecranon, proximal
      ulna, and/or the humeral supracondyle. The time from injury to treatment ranged
      from 0 to 7 days. Treatments included casting without manipulation (n=86), closed
      reduction and casting (n=8), percutaneous Kirschner wire-assisted reduction and
      casting (n=7), and open reduction and casting (n=7). RESULTS: Patients were
      followed up for a mean of 2.7 (range, 1-5) years. Outcome was excellent in 93
      patients, good in 11, and fair in 4. Higher fracture grades correlated positively
      with poorer outcomes (p=0.001) and more invasive treatment (p=0.001).
      Nonetheless, the post-reduction angles of all the patients were not significantly
      different (p>0.05). Older children sustained more severe fractures (p=0.04) and
      had poorer outcomes, even after correction for fracture grade (p=0.007). Patients
      with associated fractures had significantly poorer outcomes (p<0.05). Two
      patients developed synostosis of the proximal radioulnar joint. One of whom had
      an associated olecranon fracture and underwent open reduction and casting. The
      other had an associated proximal ulnar fracture and underwent repeated
      percutaneous Kirschner wire-assisted reduction owing to loss of reduction. Five
      patients developed heterotopic ossification. Four of whom had associated
      fractures (3 involved the olecranon and one the proximal ulna). 14 patients
      developed cubitus valgus deformity of 3o to 10o. CONCLUSION: Open reduction
      should only be performed after more conservative treatments fail to achieve
      reduction.

PMID- 21857048
TI  - Tuberculosis of the foot and ankle in children.
AB  - PURPOSE: To report manifestations and management of tuberculosis of the foot and
      ankle in 21 children. METHODS: Records of 12 girls and 9 boys aged 3 to 14 (mean,
      7) years with tuberculosis of the foot and ankle were reviewed. The mean delay in
      presentation was 4.7 (range, 0.5-14) months. All the patients had local swelling,
      tenderness, and antalgic gait; 16 were limping; 5 had an antecedent trauma; 11
      had an abscess; and 6 had a discharging sinus. The diagnosis was based on a smear
      positive for acid-fast bacilli (n=2), histopathology (n=15), or
      clinicoradiological findings (n=4). Nine patients had osteoarticular tuberculosis
      in other parts of the body. None had evidence of pulmonary tuberculosis. Lesions
      were classified into synovial (articular) and osseous. All 3 synovial lesions
      occurred in the ankle, 2 of which were at an advanced stage. Osseous lesions
      occurred in the calcaneus (n=5), metatarsal (n=5), talus (n=3), cuboid (n=3),
      medial cuneiform (n=1), and phalanx (n=1), and were sub-classified into stages 1
      (n=3), 2 (n=5), and 3 (n=10) according to disease progression. All the patients
      were treated conservatively with splintage and chemotherapy. RESULTS: The mean
      follow-up period was 21 (range, 7-51) months. All the 3 patients with stage 1
      osseous lesions showed healing within 6 weeks and had complete recovery of
      function. Four of the 5 patients with stage 2 lesions also showed complete
      recovery of function and reformation of bony trabeculations; radiological
      incorporation of sequestrum was obvious by 6 months in most patients. In patients
      with stage 3 lesions, healing was delayed and there was residual alteration in
      bony architecture and joint changes. Sclerotic changes and joint involvement also
      increased the likelihood of poor outcomes. However, none of our patients had any
      residual tenderness or foot deformity at the final follow-up. CONCLUSION: Outcome
      after non-operative treatment is good, provided the lesions are treated early.

PMID- 21857049
TI  - Giant cell tumour of the tendon sheath of the hand.
AB  - PURPOSE: To review outcomes of 106 patients after complete excision of the giant
      cell tumour of the tendon sheath of the hand, with or without postoperative
      radiotherapy. METHODS: Records of 77 women and 29 men aged 11 to 61 (mean, 31)
      years who underwent excision of giant cell tumours of the tendon sheath of the
      hand were reviewed. All patients presented with gradually progressive swelling;
      only 3 of them also presented with pain. The lesions were located on the dorsal
      aspect (n=11), the palmar aspect (n=66), both aspects (n=10), or
      circumferentially (n=14). No patient had multiple lesions. Five patients had bony
      erosion and 3 had neurovascular bundle involvement. RESULTS: The mean follow-up
      period was 12 (range, 4-22) years. 56 patients with well-encapsulated giant cell
      tumour in the palmer and/or dorsal aspects were classified as at low risk of
      recurrence. The remaining 50 patients were classified as at high risk of
      recurrence and underwent postoperative radiotherapy. None of the patients at low
      risk had any recurrence; 4 of those at high risk had recurrence despite
      radiotherapy. No complication was attributable to the irradiation, except that 3
      patients had some dark pigmentation around the wound scar. CONCLUSION:
      Postoperative radiotherapy may have a role in reducing recurrence of the giant
      cell tumour of the tendon sheath of the hand.

PMID- 21857050
TI  - Anterior cruciate ligament reconstruction using the medial third of the patellar
      tendon.
AB  - PURPOSE: To evaluate the mid-term outcome of anterior cruciate ligament (ACL)
      reconstruction using the medial third of the patellar tendon as the bone-patellar
      tendon-bone (BPTB) graft. METHODS: 79 men (34 right knees and 45 left knees) aged
      20 to 52 (mean, 28) years underwent ACL reconstruction using the medial third of
      the patellar tendon with bone plugs and were followed up for a minimum of 3
      years. Stability was assessed using the Lachman test and the pivot shift test.
      The range of motion, donor-site symptoms, Lysholm knee score, and International
      Knee Documentation Committee (IKDC) score were also recorded. RESULTS: In terms
      of stability, only 4 patients had a grade-2 laxity postoperatively, compared to
      all having a grade-2 or -3 laxity preoperatively. Regarding the range of motion,
      extension loss was <3o in 76 patients and 3o to 5o in 3, whereas flexion loss was
      <5o in 73 patients, 5o to 15o in 5, and 16o to 25o in one. No patient had
      patellar tendon rupture/shortening, patellar fracture, or patellar maltracking.
      The mean Lysholm knee score improved from 48 to 92 (p<0.0001); scores were
      excellent (>90) in 46 patients and good (83-90) in 32 patients. The overall IKDC
      score was grade A (normal) in 9 patients, grade B (near normal) in 66, and grade
      C (abnormal) in 4. Three of the latter patients had osteoarthritic changes and
      pain on minimal physical activity. Only one patient had a sensation of partial
      giving way during moderate physical activity. 20% of the patients had anterior
      knee pain. CONCLUSION: Outcome of ACL reconstruction using the medial third of
      the patellar tendon was comparable to that using the central third of the
      patellar tendon. In addition, there were no instances of patellar tendon
      rupture/shortening, patellar fracture, or patellar maltracking.

PMID- 21857051
TI  - High-flexion versus conventional total knee arthroplasty: a 5-year study.
AB  - PURPOSE: To compare mid-term outcomes of a high-flexion prosthesis with a
      conventional prosthesis. METHODS: Records of 107 consecutive patients who
      underwent total knee arthroplasty (TKA) for primary osteoarthritis by a single
      surgeon were reviewed. 21 men and 36 women (mean age, 65 years) used a high
      flexion prosthesis (NexGen CR-Flex Mobile, Zimmer), whereas 38 men and 12 women
      (mean age, 67 years) used a conventional prosthesis (Genesis II, Smith & Nephew)
      that preserves the posterior cruciate ligament, with mobile-bearing polyethylene
      inlay. The Knee Society knee and functional scores and the range of motion
      (especially maximum passive flexion) were assessed. Radiographs were evaluated to
      identify radiolucent lines at the bone cement interface, patella tracking,
      tibiofemoral alignment, and implant positioning. RESULTS: The mean follow-up
      period was 68 (range, 51- 70) months. In terms of the mean Knee Society scores
      and range of motion, the difference between groups was not significant (p>0.05),
      but the improvement in both groups after TKA was significant (p<0.005).
      Respectively in the high-flexion and conventional TKA groups, 2 and one of the
      patients developed deep vein thrombosis and were treated with anticoagulants for
      3 months. One and 5 of the patients had an unsatisfactory range of motion (<60o)
      in week 1, which was resolved with mobilisation under general anaesthesia in
      combination with a peridural catheter for analgesia. No patient developed implant
      specific complications such as aseptic loosening (osteolysis, progressive
      radiolucent lines, implant deviation) or dislocation of the polyethylene insert.
      CONCLUSION: The high-flexion prosthesis revealed no significant advantages over
      the conventional prosthesis in terms of the Knee Society scores and range of
      motion. Long-term studies are needed to determine whether the high-flexion
      implant is superior to the conventional implant in terms of polyethylene wear and
      aseptic loosening.

PMID- 21857052
TI  - Effect of medial soft-tissue releases during posterior-stabilised total knee
      arthroplasty.
AB  - PURPOSE: To assess the effect of each step of medial soft-tissue releases on the
      joint gap angle during posterior-stabilised total knee arthroplasty (TKA).
      METHODS: 82 women and 9 men (mean age, 72 years) with medial osteoarthritic knees
      underwent 100 posterior-stabilised TKAs, in which release of superficial fibres
      of the medial collateral ligament (MCL) were required using the gap control
      technique. The order of releases was the superficial MCL, the pes anserinus, and
      then the semi-membranosus. The superficial MCL was released selectively. The
      effect of each step of medial soft-tissue releases in full extension and in 90o
      flexion was compared. RESULTS: After all medial soft-tissue releases, the mean
      joint gap angles decreased from 8.7o to 3.8o varus in flexion and from 4.4o to
      1.4o varus in extension. The total effect of medial soft-tissue releases was
      significantly larger in flexion than in extension (4.9o+/-3.2o vs. 3.0o+/-2.0o,
      p<0.0001), except for the release of posterior fibres of the superficial MCL. The
      effect of release of the semi-membranosus in flexion was largest. CONCLUSION: The
      release effect was significantly greater in flexion than in extension during
      posterior-stabilised TKA; the joint gap technique may be more reliable in medial
      osteoarthritic knees with moderate and severe varus instability.

PMID- 21857053
TI  - Sterile surgical helmet system in elective total hip and knee arthroplasty.
AB  - PURPOSE: To evaluate the sterility of the sterile surgical helmet system (SSHS)
      during elective total hip and knee arthroplasty in theatres with (n=20) and
      without (n=20) laminar flow. METHODS: Three surgeons performed 14 total knee
      arthroplasties (TKAs) and 6 total hip arthroplasties (THAs) in a laminar flow
      theatre and 15 TKAs and 5 THAs in a non-laminar flow theatre. An SSHS was used in
      all the procedures. Samples were taken from the hood at 30-minute intervals
      during surgery. Swabs were then broken into cooked meat broths for cultivation of
      organisms. The broths were then directly inoculated onto blood agar and
      fastidious anaerobic agar for culture of aerobic and anaerobic bacteria,
      respectively. After 24 hours, these plates were reinoculated with broths that had
      been incubated for 24 hours. Microbial growth was quantified as 0 (none), 1
      (mild), 2 (moderate) and 3 (heavy). Bacterial contamination in the 2 groups at
      30, 60 and 90 minutes was compared. RESULTS: Respectively in the laminar and non
      laminar flow theatres, 0 and 9 of the SSHSs showed bacterial growth after direct
      inoculation, and 14 and 18 of the SSHSs grew 18 and 24 types of organisms in the
      swab cultures after 24 hours of incubation. Respectively at 30, 60, and 90
      minutes, the degree of contamination from direct incubation was significant, but
      the degree of contamination on swabs after 24 hours of inoculation was not
      significant. The mean time-dependent contamination after direct inoculation was 0
      for the laminar flow group and 0.5, 0.75, and 1.0 for the non-laminar flow group,
      whereas the corresponding values after 24 hours of incubation were 1.8, 1.8, and
      2.6, and 2, 2.75, and 2.95. Coagulase negative Staphylococcus aureus was the most
      common organism in both groups. CONCLUSION: 80% of SSHSs used were contaminated
      intra-operatively. Direct contact with the SSHS should be avoided by the
      operating team during surgery. Routine changing of gloves in case of contact with
      the SSHS should be practised.

PMID- 21857054
TI  - Review article: bone defect classifications in revision total knee arthroplasty.
AB  - There are several classification systems for bone defects in revision total knee
      arthroplasty. Each has its own drawbacks, and none satisfies all the clinical
      demands. Therefore, a new classification system and treatment guideline based on
      a combination of criteria (location, side, containment, and severity of the bone
      defect) is necessary.

PMID- 21857055
TI  - Sacroiliitis caused by Salmonella typhi: a case report.
AB  - Sacroiliitis caused by Salmonella typhi is rare. In India, unilateral
      sacroiliitis is usually caused by tuberculosis. We report a 22-year-old man who
      presented with a high-grade fever and positive blood culture for Salmonella
      typhi. The patient was treated with intravenous vancomycin and levofloxacin for
      15 days and then oral levofloxacin for 6 weeks.

PMID- 21857056
TI  - Chondromyxoid fibroma of the lateral malleolus: a case report.
AB  - Chondromyxoid fibromas account for <1% of primary bone neoplasms. We report one
      such case occurring in the distal fibula of a 27-year-old woman. The patient
      underwent curettage, followed by phenolisation, insertion of a Steinmann pin, and
      cementation. This treatment reduced morbidity, restored stability, and enabled
      rapid functional recovery. There was no recurrence after 2 years.

PMID- 21857057
TI  - Breakage of an intramedullary rod after bone union in congenital pseudoarthrosis
      of the tibia: a report of two cases.
AB  - We report 2 patients with congenital pseudoarthrosis of the tibia who underwent
      intramedullary Rush rod transfixation through the ankle joint following
      refracture and nonunion of vascularised fibular grafting 6 and 8 months earlier.
      After 9 and 5 years, both Rush rods were broken at the level of the ankle joints,
      while the reconstructed area was solidly united. The growth of the distal tibia
      increased the distance of the tips of the broken rod and hence the ankle joint
      motion. The broken tips may damage the articular cartilage and result in valgus
      deformity of the ankle and limb length discrepancy.

PMID- 21857058
TI  - Dysplasia epiphysealis hemimelica of the ankle joint: a case report.
AB  - Dysplasia epiphysealis hemimelica is a rare non-hereditary epiphyseal disease
      that mimics synovial chondromatosis of the joints. The disease mainly targets
      long bones of the lower extremities and tarsal bones. We report one such case
      manifesting in the lateral tibia of a 13-year-old boy. He presented with a 7
      month history of pain and a bony mass (3x4 cm) at the right ankle. The mass
      restricted ankle dorsiflexion over the lateral malleolar area. It was ossific
      with a lobulated appearance and reached the marrow with the underlying epiphysis
      and adjacent bones. The mass was excised completely from the epiphysis. The
      detached syndesmos was sutured anatomically.

PMID- 21857059
TI  - Chronic closed transection of the biceps brachii: a case report.
AB  - A 32-year-old man presented with chronic closed transection of the biceps brachii
      of the right arm after 30 months of conservative treatment. Magnetic resonance
      imaging showed atrophy of both long and short heads of the biceps brachii, with a
      5-cm defect secondary to proximal and distal retraction on either side of the
      tear. There was a similar defect in the coracobrachialis, but the triceps brachii
      was normal. The self-rated overall arm status was 4 out of 10 (using a visual
      analogue scale). Objective functional deficit was measured using a dynamometer.
      Forearm flexion and supination strength of each arm at 120o/s was tested. The
      patient had a 34% deficit (40 vs. 61 Nm) in peak torque during forearm flexion
      and a 22% deficit (10 vs. 12 Nm) during forearm supination. The patient could not
      maintain maximal torque throughout the range of motion, with an approximately 50%
      deficit in the later part of the range of motion. The patient underwent
      reconstruction of the biceps brachii using an interposition Achilles tendon
      allograft.

PMID- 21857060
TI  - Unipolar versus bipolar uncemented hemiarthroplasty for elderly patients with
      displaced intracapsular femoral neck fractures.

PMID- 21857061
TI  - Mechanical thromboprophylaxis for patients undergoing hip fracture surgery.

PMID- 21857062
TI  - Use of a cement-loaded Kuntscher nail in first-stage revision hip arthroplasty
      for massive femoral bone loss secondary to infection: a report of four cases.

PMID- 21857063
TI  - Advances in meniscal tissue engineering.
AB  - Injuries and lesions to the meniscal cartilage of the knee joint are common. As a
      result of its limited regenerative capacity, early degenerative changes to the
      articular surface frequently occur, resulting in pain and poor function.
      Currently available surgical interventions include repair of tears, and partial
      and total meniscectomy but the results are inconsistent and often poor. Interest
      in the field of meniscal tissue engineering with the possibilities of better
      treatment outcomes has grown in recent times. Current research has focused on the
      use of mesenchymal stem cells, fibrochondrocytes, meniscal derived cells and
      fibroblast-like synoviocytes in tissue engineering. Mesenchymal stem cells are
      multipotent cells that have been identified in a number of tissues including bone
      marrow and synovium. Current research is aimed at defining the correct
      combination of cytokines and growth factors necessary to induce specific tissue
      formation and includes transforming growth factor-beta (TGF-beta), Platelet
      Derived Growth Factor (PDGF) and Fibroblast Growth Factor 2 (FGF2). Scaffolds
      provide mechanical stability and integrity, and supply a template for three
      dimensional organization of the developing tissue. A number of experimental and
      animal models have been used to investigate the ideal scaffolds for meniscal
      tissue engineering. The ideal scaffold for meniscal tissue engineering has not
      been identified but biodegradable scaffolds have shown the most promising
      results. In addition to poly-glycolic acid (PGA) and poly-lactic acid (PLLA)
      scaffolds, new synthetic hydrogels and collagen sponges are also being explored.
      There are two synthetic meniscal implants currently in clinical use and there are
      a number of clinical trials in the literature with good short- and medium-term
      results. Both products are indicated for segmental tissue loss and not for
      complete meniscal replacement. The long-term results of these implants are
      unknown and we wait to see whether they will be proved to have benefits in
      delaying arthritic change and chondral damage.

PMID- 21857064
TI  - Current concepts in the treatment of cartilage lesions with special regard to the
      knee joint.
AB  - The last twenty years have been marked by a rapid development of articular
      cartilage treatment and regeneration techniques. We present current concepts in
      the treatment of cartilage lesions and injuries, including gene therapy and
      tissue engineering.

PMID- 21857065
TI  - Interrater and intrarater reliability of lumbar spine magnetic resonance
      assessment of military aircraft pilot candidates.
AB  - BACKGROUND: The development of diagnostic imaging facilitates evaluation of
      spinal anatomy, but there is no full correspondence between morphologic and
      pathologic changes observed in radiographic studies and clinical findings. The
      aim of the study was to: 1. Evaluate the degree of signal intensity and
      degenerative changes of intervertebral discs in the lumbar spine on MRI. 2.
      Estimate interrater reliability of classification of pathology between
      experienced and inexperienced medical doctors. MATERIAL AND METHOD: The sample
      consisted of 89 persons aged between 18 and 21 years. MRI scans of the lumbar
      spine were evaluated by the use of a console for digital analysis by three
      medical doctors with different levels of experience. RESULTS: Evidence of
      dehydration of intervertebral disc was found in 3.37%-4.49% at the L4-L5 level,
      and in 13.48%-15.73% of cases at the L5-S1 level. Interrater reliability ranged
      from full agreement at levels where degenerative changes are rarely observed to
      fair and poor agreement at L4-L5 and L5-S1. Intrarater reliability showed full
      agreement on higher levels to good and very good at l4-l5 and l5-S1 levels.
      Interrater reliability concerning the degree of degenerative changes was 0.6 for
      Th12 to L4, but was poor at L4-L5 and L5-S1. Intrarater reliability ranged from
      full agreement at higher levels to poor at L3-L4-L5 and moderate at L5-S1.
      CONCLUSIONS: 1. Asymptomatic intervertebral disk changes were found in 30% of the
      study participants. 2. Evaluation of the degree of degenerative changes of
      intervertebral discs requires specialist training and experience.

PMID- 21857066
TI  - Evaluation of the effectiveness of short-term rehabilitation of women with
      chronic low back pain using the Oswestry and Roland-Morris Disability Scales.
AB  - BACKGROUND: 60-80% of the population experience chronic low back pain at some
      point in their lives [1], with women suffering more frequently [2]. Low back pain
      related ailments lead to long-term or recurrent disability [3, 4]. Rehabilitation
      based on physiotherapy provides a viable alternative and is rightly regarded as
      safer for patients. However, finding an effective method of rehabilitation is a
      difficult task [5, 6]. The aim of this study was to compare the outcomes of
      rehabilitation in women with chronic low back pain using the Oswestry and Roland
      Morris Disability Scales and to identify factors influencing the degree of
      functional disability in patients with chronic low back pain. MATERIAL AND
      METHODS: The study involved 319 women aged 18-75 years (mean age = 45 years, SD
      +/- 16. 3). The participants were undergoing treatment at the Rehabilitation
      Centre of Zamosc University of Management and Administration on account of
      chronic low back pain, following two or more episodes lasting longer than three
      months. The outcomes of rehabilitation were assessed with ODI and RMDQ. RESULTS:
      We obtained comparable results with the ODI and RMDQ and found statistically
      significant improvement in functional status after rehabilitation (ODI: p <0.001,
      RMDQ: p <0.001). In both cases there was a statistically significant relationship
      between the degree of functional disability and age (ODI: p <0.001, RMDQ: p
      <0.001), education (ODI: p <0.004, RMDQ: p <0.004), BMI (ODI: p <0.001, RMDQ : p
      <0.001), WHR (ODI: p <0.001, RMDQ: p <0.001), and hypertension (ODI: p <0.001,
      RMDQ: p <0.001). There were no statically significant differences between the
      degree of disability vs. place of residence (ODI: p <0.5, RMDQ: p <0.867) or the
      presence of type 2 diabetes (ODI: p <0.321, RMDQ: p <0.06). CONCLUSIONS: 1.The
      programme for rehabilitation of patients with low back pain proved effective in
      reducing the degree of disability, as demonstrated both by the Oswestry
      Disability Index and the Roland-Morris Disability Questionnaire. 2. The
      relationship between the degree of functional disability and age, BMI, WHR, and
      hypertension was also confirmed by both questionnaires.

PMID- 21857067
TI  - Pain control in patients with chronic back pain syndrome.
AB  - BACKGROUND: Back pain syndrome is a common problem, not only orthopedic, but also
      psychological, social and economic. In research and clinical practice, the
      tendency to differentiate between physiological aspects of pain and the
      psychological, social and economic factors related to pain is dominant. The goal
      of this paper is to evaluate pain control perception in patients with chronic
      back pain syndrome. MATERIAL AND METHODS: The sample consisted of 57 subjects,
      including 41 females and 16 males suffering from back pain syndrome. The mean age
      of the subjects was 60 years and the mean period of the disease was 10 years.
      Pain intensity and motor activity limitation were assessed using a modified
      Laitinen questionnaire and BPCQ questionnaire developed by S.Skevington. RESULTS:
      66% of the subjects reported very intense and intense pain; almost half of the
      respondents reported limitation of their everyday activities resulting from pain.
      Among the studied 3 dimensions of pain control perception, external control
      (powerful doctors) and chance loci were dominant. A detailed analysis of pain
      control factors revealed great diversity in the replies; none of the reported
      loci of control was dominant. As compared to the cited English study, the
      powerful doctors locus was far more seldom reported by our study subjects.
      CONCLUSIONS: Every third subject reported the desired dimensions of pain control
      (internal strong or undifferentiated strong types). The obtain results suggest
      helplessness and lack of self-control of pain among the studied sample.

PMID- 21857068
TI  - Arthroscopic assessment of intraarticular distal radius fractures--results of
      minimally invasive fixation.
AB  - BACKGROUND: For many years, wrist arthroscopy has been used to diagnose and treat
      soft tissue lesions and to restore anatomic articular surface alignment in
      intraarticular fractures. However, there are no publications providing clear and
      precise indications for wrist arthroscopy in distal radius fractures. The aim of
      the study was to analyse factors influencing the outcomes of intraarticular
      distal radius fracture treatment with K-wire fixation under arthroscopic guidance
      in AO B1 and C1 type fractures. MATERIAL AND METHOD: A group of 26 patients (27
      wrists) following an arthroscopic procedure (ARTR group) was the prospective
      component and 27 patients (27 wrists) following a non-arthroscopic procedure (OP
      group) constituted the retrospective part of the trial. Both groups consisted
      only of patients with B1 and C1 type fractures (10 and 17, respectively)
      according to the AO classification. RESULTS: In the ARTR group, there was a
      marked (statistically significant) difference between radiologically and
      arthroscopically assessed displacement. This underestimation of displacement was
      higher in B1 than C1 type fractures (statistically significant difference).
      Numerous associated injuries were identified, such as carpal bone cartilage
      injuries (85.19%), TFCC injury (59.26%) and SL ligament injuries (40.74%). Loose
      bodies were detected in 66.7% of the patients. In B1 type fractures, the most
      common ligamentous injury was a SL ligament lesion (50%), while in C1 fractures
      it was a TFCC lesion (70.59%). Comparing both groups (ARTR and OP), better
      clinical outcomes were observed in the ARTR group (though not statistically
      significant), with the most marked differences noted with regard to B1 type
      fractures. CONCLUSIONS: In B1 and C1 type intraarticular distal radius fractures,
      displacement visible during arthroscopy was greater than that seen on primary
      radiological assessment. In B1 type fractures, the difference between
      radiological and arthroscopic evaluation of displacement was more marked than in
      C1 fractures. It means that B1 type fractures can be highly "misleading", because
      their radiological pattern suggested little displacement, while actual
      displacement was more pronounced. On the basis of our results, it might be
      concluded that wrist arthroscopy could become a standard, routine procedure in B1
      type fractures. In C1 type fractures, the method of treatment would depend on the
      surgeon's preferences.

PMID- 21857069
TI  - Methods of diagnosis and treatment of ankle fractures--the opinion of members and
      supporters of the Polish Foot and Ankle Society.
AB  - BACKGROUND: The present paper is based on a survey distributed among the
      participants of the 3rd Congress of the Polish Foot and Ankle Society in
      Jastarnia on April 22-24, 2010. MATERIAL AND METHODS: A clinical description and
      imaging data of a hypothetical patient with a typical ankle fracture were used to
      identify current methods of diagnosis and treatment of such injuries in Poland.
      The participants were orthopaedists. Eighty-five questionnaires were distributed
      and 54 (63%) were completed and returned. RESULTS AND CONCLUSIONS: Most
      respondents correctly recognized the fracture mechanism and identified the type
      of fracture. They preferred operative treatment, but were not able to apply the
      AO classification. The answers regarding post-operative radiological follow-up
      did not provide for long-term follow-up and the suggested methods of imaging to
      detect disruption of the tibiofibular syndesmosis were insufficient. The
      recommendations concerning the timing and staging of post-operative weight
      bearing as well as antithrombotic prophylaxis complied with current standards.

PMID- 21857070
TI  - A modified technique of using the dynamic external finger fixation system. Case
      study.
AB  - Fractures of the phalangeal joints of the hand present a challenging problem
      because of the small size of the fracture fragments, limiting internal fixation,
      and their articular nature necessitating early mobilisation to ensure good
      results. We present a case of a patient presenting with an open displaced
      intraarticular fracture of the metacarpophalangeal joint that was managed with
      limited internal fixation with a Kirschner wire along with the S-Quattro. The
      fracture united and the patient returned to his previous occupation with no
      limitations in his activities of daily living. This is the first instance of S
      Quattro being described for the management of an open fracture with the
      additional use of limited internal fixation. The additional use of limited
      internal fixation ensured adequate fracture reduction and stabilisation. The S
      Quattro application does not require significant soft tissue dissection, making
      it particularly suited to open fractures.

PMID- 21857071
TI  - Femoral insufficiency fractures with bisphosphonate therapy. Cases study.
AB  - The aim of this paper is to analyze on clinical cases specific features of
      femoral insufficiency fractures during bisphosphonates therapy. We are presenting
      two insufficiency femoral fractures (2 patients) in patients receiving
      bisphosphonate therapy. These two cases represent new type of femoral fractures.
      These are low energy or spontaneous fractures of diaphysis and subtrochanteric
      region. Prodromal pain is often observed. On x-rays thick lateral cortex, its
      ellipsoid thickening and transverse or oblique fracture line is observed. Many
      authors link such fractures to long-term bisphosphonate therapy. Patients on long
      term bisphosphonate therapy present with new and specific fracture pattern of
      femoral bone. Fractures of this pattern are extremely rare. The risk benefit
      ratio of bisphosphonates therapy is not changed.

PMID- 21857072
TI  - Therapeutic potential of adenosine analogues and conjugates.
AB  - This review summarizes current knowledge of adenosine analogues and conjugates
      with promising therapeutic properties. Adenosine is a signaling molecule that
      triggers numerous physiological responses. It acts through the adenosine
      receptors (ARs), belonging to the family of G-protein-coupled receptors and
      widely distributed throughout the body. Moreover, adenosine is involved in key
      biochemical processes as a part of ATP, the universal energy currency. Thus,
      compounds that are analogues of adenosine and its conjugates have been
      extensively studied as potential therapeutics. Many inhibitors of ARs are in
      clinical trials as promising agents in treatment of inflammation, type 2
      diabetes, arrhythmia and as vasodilators used in the myocardial perfusion imaging
      (MPI) stress test. Furthermore, adenosine analogues revealed high efficacy as
      enzyme inhibitors, tested for antitrypanosomal action and as bivalent ligands and
      adenosine-oligoarginine conjugates as inhibitors of protein kinases.

PMID- 21857073
TI  - Role of vinpocetine in cerebrovascular diseases.
AB  - A cerebrovascular accident, or stroke, is defined as the abrupt onset of a
      neurological deficit, which can be due to ischemia. Cerebral ischemia is caused
      by a reduction in blood flow that thereby decreases cerebral metabolism. Chronic
      cerebral hypoperfusion leads to irreversible brain damage and plays an important
      role in the development of certain types of dementia. Vinpocetine, chemically
      known as ethyl apovincaminate, is a vinca alkaloid that exhibits cerebral blood
      flow enhancing and neuroprotective effects. Non-clinical and clinical studies
      have suggested multiple mechanisms responsible for the beneficial neuroprotective
      effects of vinpocetine. As no significant side effects related to vinpocetine
      treatment have been reported, it is considered to be safe for long-term use. This
      vasoactive alkaloid is widely marketed as a supplement for vasodilation and as a
      nootropic for the improvement of memory. The present review focuses on studies
      investigating the role of vinpocetine in cerebrovascular diseases.

PMID- 21857074
TI  - Treatment of inflammatory bowel disease (IBD).
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the
      gastrointestinal tract, which includes Crohn's disease (CD) and ulcerative
      colitis (UC). These diseases have become important health problems. Medical
      therapy for IBD has advanced dramatically in the last decade with the
      introduction of targeted biologic therapies, the optimization of older therapies,
      including rugs such as immunomodulators and 5-aminosalicylic acid (5-ASA), and a
      better understanding of the mucosal immune system and the genetics involved in
      the pathogenesis of IBD. The goal of IBD therapy is to induce and maintain
      remission. The current treatment paradigm involves a step-up approach, moving to
      aggressive, powerful therapies only when milder therapies with fewer potential
      side effects fail or when patients declare themselves to have an aggressive
      disease. This review focuses on the current treatments for inflammatory bowel
      disease.

PMID- 21857075
TI  - Activity of essential phospholipids (EPL) from soybean in liver diseases.
AB  - Essential phospholipids (EPL) contain a highly purified extract of
      polyenylphosphatidylcholine (PPC) molecules from soybean. The main active
      ingredient is 1,2-dilinoleoylphosphatidylcholine (DLPC), which differentiates it
      from other phospholipids, lecithins, or extracts from other sources. Although
      EPLis widely used in liver diseases of various origins, its mode of action and
      pharmacological and clinical evidence of its efficacy have not yet been concisely
      reviewed. This paper critically summarizes experimental and clinical results.
      With regard to in-vitro and animal tests, EPL influenced membrane-dependent
      cellular functions and showed anti-oxidant, anti-inflammatory, anti-fibrotic,
      apoptosis-modulating, regenerative, membrane-repairing and -protective, cell
      signaling and receptor-influencing, as well as lipid-regulating effects in
      intoxication models with chemicals or drugs. Clinical studies, primarily from
      European and Asian countries, have shown improvement in subjective symptoms;
      clinical, biochemical and imaging findings; and histology in liver indications
      such as fatty liver of different origin, drug hepatotoxicity, and adjuvant in
      chronic viral hepatitis and hepatic coma. The available studies characterize EPL
      as evidence-based medicine, although further long-term controlled clinical trials
      are required to precisely determine its benefit for alleviating symptoms,
      improving well-being, inducing histological changes and slowing the progression
      of liver disease. EPL-related relevant side effects were not observed.

PMID- 21857076
TI  - Thymoquinone produced antianxiety-like effects in mice through modulation of GABA
      and NO levels.
AB  - The aim of the present study was to investigate the role of GABAergic and
      nitriergic modulation in the antianxiety effect of thymoquinone, a major
      constituent of Nigella sativa, in mice under unstressed and stressed conditions.
      Thymoquinone (10 and 20 mg/kg), methylene blue (1 mg/kg) and diazepam (2 mg/kg)
      were administered followed by behavioral testing using an elevated plus maze, the
      light/dark test and the social interaction test in both unstressed and stressed
      mice (mice subjected to 6 h immobilization). The effects of the above-mentioned
      drugs on plasma nitrite, a stable metabolite of nitric oxide (NO) and brain GABA
      content were also studied. Diazepam (2 mg/kg) produced significant anxiolytic
      like effects only in unstressed mice. However, diazepam significantly increased
      the GABA content in both unstressed and stressed mice as compared with their
      respective control groups. Thymoquinone (10 and 20 mg/kg) produced significant
      antianxiety effects in unstressed mice without altering nitrite levels, but only
      the higher dose (20 mg/kg) of thymoquinone increased the GABA content in
      unstressed mice. In stressed mice, thymoquinone (20 mg/kg) showed anxiolytic
      effects, with a significant decrease in plasma nitrite and reversal of the
      decreased brain GABA content. Pre-treatment with methylene blue enhanced the
      antianxiety effect of thymoquinone in both unstressed and stressed mice.
      Therefore, the present study suggests an involvement of NO-cGMP and GABAergic
      pathways in the anxiolytic-like activity of thymoquinone.

PMID- 21857077
TI  - AM251, cannabinoids receptors ligand, improves recognition memory in rats.
AB  - High density of cannabinoid receptors type 1 (CB1) in the brain suggests that
      endocannabinoid system plays an important role in the functioning of the central
      nervous system. Natural and synthetic cannabinoids are known to attenuate
      learning and memory processes. The adverse effects of cannabinoids are reversed
      by SR141716A, at first reported to be a selective CB1 receptor antagonist, later
      shown to possess also inverse agonist properties. The present study was performed
      in an attempt to determine the influence of different doses of AM251, a member of
      the same cannabinoid group as SR141716A, on recognition memory evaluated in an
      object recognition test. Because cannabinoids may alter motor function and affect
      anxiety, the influence of AM251 on psychomotor activity and anxiety was assessed
      in an "open-field" test and elevated plus maze, respectively. While the lowest
      dose of AM251 (1.0 mg/kg) significantly improved recognition memory, higher doses
      (2.5 mg/kg and 5.0 mg/kg) did not have an influence on it. Moreover, AM251 did
      not affect anxiety but in the highest dose significantly attenuated psychomotor
      activity in rats. The main finding of the present study indicates that AM251, at
      the dose of 1.0 mg/kg, improves recognition memory in rats without alteration of
      their psychomotor activity and anxiety. The pro-cognitive effect exerted by
      compounds belonging like AM251 to diarylpyrazole group may be beneficial in
      therapeutic use of these compounds, especially in patients with cognitive
      dysfunctions.

PMID- 21857078
TI  - Effect of nitric oxide synthase inhibitors on benzodiazepine withdrawal in mice
      and rats.
AB  - This study was undertaken to evaluate the effect of nitric oxide (NO) synthase
      inhibitors on benzodiazepine withdrawal syndrome in mice and rats. Diazepam
      withdrawal in mice was read out as intensification of the seizures induced by a
      subthreshold dose of pentetrazole. In rats, the withdrawal syndrome resulting
      from chronic administration of diazepam, chlordiazepoxide, clonazepam and
      temazepam was characterized by audiogenic seizures, hypermotility and weight
      loss. Administration of the non-selective NO synthase inhibitors N(G)-nitro-L
      arginine (L-NOARG) and N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME)
      significantly attenuated the withdrawal syndrome (i.e., pentetrazole-induced
      seizures) in diazepam-dependent mice. L-NOARG significantly suppressed
      hypermotility in clonazepam-dependent rats and inhibited the decrease in body
      weight observed after 12 h of withdrawal in chlordiazepoxide- and clonazepam
      dependent rats. Moreover, a clear propensity of L-NOARG to protect benzodiazepine
      dependent rats against audiogenic seizures was observed. These findings suggest
      that the cGMP/NO system may participate in causing the signs of benzodiazepine
      withdrawal.

PMID- 21857079
TI  - Nefopam enhances the protective activity of antiepileptics against maximal
      electroshock-induced convulsions in mice.
AB  - Nefopam is a centrally acting non-opioid analgesic with a mechanism of action
      that is not completely understood. Adverse effects associated with the
      therapeutic use and overdose of nefopam are mainly associated with the central
      nervous system, such as hallucinations, cerebral edema and convulsions. The aim
      of this study was to assess the effect of nefopam on the electrical threshold and
      its influence on the protective activity of antiepileptic drugs in the maximal
      electroshock test in mice. A 5 mg/kg dose of nefopam significantly elevated the
      electric seizure threshold, while a dose of 1 mg/kg failed to protect mice
      against electroconvulsion. At a subthreshold dose of 1 mg/kg, nefopam
      significantly enhanced the anticonvulsant activity of valproate against
      electroconvulsions. The protective activity of phenobarbital and phenytoin was
      significantly enhanced by co-administration of nefopam at the 5 mg/kg dose, but
      this same dose of nefopam failed to affect the protective activity of
      carbamazepine. In conclusion, nefopam exerts an anticonvulsive effect when given
      alone and significantly enhances the protective activity of certain antiepileptic
      agents against electroconvulsions induced in mice.

PMID- 21857080
TI  - Riluzole prevents morphine-induced apoptosis in rat cerebral cortex.
AB  - Neuronal apoptosis has been shown to be associated with the development of
      tolerance to morphine. In the present study, we investigated the effect of
      intracerebroventricular (icv) administration of an inhibitor of glutamate
      release, riluzole, on morphine-induced apoptosis in the rat cerebral cortex.
      Various groups of rats received either morphine (intraperitoneally, ip) and
      vehicle (icv) or morphine (ip) and different doses of riluzole (icv) once per day
      for 8 days. An in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end-labeling (TUNEL) method was used as an apoptosis assay. Levels of the
      anti-apoptotic factors Bcl-2 and HSP70 and the pro-apoptotic agent caspase-3 were
      evaluated by immunoblotting. The glutamate concentration in the cerebral cortex
      was measured by high performance liquid chromatography (HPLC). The results showed
      that icv administration of riluzole decreased the number of apoptotic cells in
      the cerebral cortex compared with the control group, which was treated with
      morphine (ip) and 1% Tween 80 in 0.9% normal saline (icv). The levels of the anti
      apoptotic proteins Bcl-2 and HSP70 were higher in the riluzole groups than in the
      control. Furthermore, co-administration of riluzole with morphine significantly
      decreased caspase-3 protein levels and glutamate content of the cerebral cortex
      compared with the control. In conclusion, we found that icv administration of
      riluzole attenuates morphine-induced apoptosis in the cerebral cortex after the
      development of morphine tolerance.

PMID- 21857081
TI  - Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1
      auditory cells.
AB  - Cisplatin is a highly effective chemotherapeutic agent, but it has significant
      ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell
      loss following exposure to cisplatin. The present study examined the effects of
      phloretin, a natural polyphenolic compound found in apples and pears, on
      cisplatin-induced apoptosis. We found that phloretin induced the expression of
      heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner.
      Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear
      translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression
      of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein
      kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin
      induced HO-1 expression. Phloretin protected the cells against cisplatin-induced
      apoptosis. The protective effect of phloretin was abrogated by zinc
      protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment
      inhibited mitochondrial dysfunction and the activation of caspases. These results
      demonstrate that the expression of HO-1 induced by phloretin is mediated by both
      the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in
      HEI-OC1 cells.

PMID- 21857082
TI  - Activation of orexin/hypocretin type 1 receptors stimulates cAMP synthesis in
      primary cultures of rat astrocytes.
AB  - The effects of orexins, which are also named hypocretins, on cAMP formation were
      examined in primary cultures of rat astrocytes. Orexin A, an agonist of OX1 and
      OX2 receptors, stimulated cAMP production with an EC50 value of 0.68 MUM and
      potentiated the forskolin-induced increase in the nucleotide synthesis. [Ala11-D
      Leu15]orexin B, an agonist of OX2 receptors, was inactive. The effects of orexin
      A were antagonized by SB 408124, a selective blocker of OX1 receptors, but were
      not affected by TCS OX2 29, a selective antagonist of OX3 receptors. We
      hypothesized that the activation of OX1 receptors stimulated cAMP synthesis in
      primary rat astrocyte cultures.

PMID- 21857083
TI  - No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in
      HepG2 cells.
AB  - Scavenging of intracellular reactive oxygen species (ROS) is one of the potential
      mechanisms contributing to the protective effects of many antioxidants. Curcumin,
      a natural product, is an effective ROS scavenger. However, the role of its ROS
      scavenging ability in its cytoprotective action remains to be clarified. Herein,
      the protective effects of curcumin on hydrogen peroxide (H2O2)- and tert-butyl
      hydroperoxide-induced ROS formation and HepG2 cell injury were determined. HepG2
      cells were pretreated with curcumin for 30 min and then treated with H2O2 (500
      MUM) or tert-butyl hydroperoxide (200 MUM) for 24 h. Curcumin pretreatment
      dramatically decreased H2O2- and tert-butyl hydroperoxide-induced ROS production,
      but failed to suppress cytotoxicity of those compounds. H2O2 induced decreases in
      mitochondrial membrane potential (DeltaPsim) and increases in DNA fragmentation
      could not be reversed by curcumin. Furthermore, curcumin enhanced expression of
      H2O2-induced pro-apoptotic protein Bax expression and inhibited expression of
      anti-apoptotic proteins Bcl-2 and Bcl-xL. In addition, curcumin significantly
      decreased p38MAPK and phospho-CDC-2 protein expression and increased phospho
      p38MAPK, p42/44MAPK, and phospho-p42/44MAPK protein expression. These results
      suggest that short pretreatment and subsequent longer co-treatment of low
      concentrations of curcumin showed no obvious protective effect on H2O2-induced
      HepG2 cell injury.

PMID- 21857084
TI  - Prevention of the wortmannin-induced inhibition of phosphoinositide 3-kinase by
      sulfhydryl reducing agents.
AB  - The effects of the sulfhydryl reducing agents 2-mercaptoethanol and
      dithiothreitol on wortmannin-induced inhibition of phosphoinositide 3-kinase
      (PI3K) were studied in order to examine whether the sulfhydryl reducing agents
      directly affect the wortmannin inhibition of PI3K. These reducing agents are
      commonly used to stabilize enzyme structures by maintaining protein sulfhydryl
      groups in the reduced state. Preincubation of wortmannin with millimolar levels
      of 2-mercaptoethanol, a sulfhydryl derivative of ethanol, markedly prevented
      subsequent wortmannin-induced inhibition of PI3K. In contrast, ethanol, 2
      mercaptoethanol lacking sulfhydryl group, and 2-(methylthio)ethanol, a methyl
      derivative of the sulfhydryl group of 2-mercaptoethanol, had little effect on the
      wortmannin-induced inhibition of PI3K, which suggests that the prevention of
      wortmannin-induced inhibition by 2-mercaptoethanol occurs through the sulfhydryl
      group of this agent. Moreover, dithiothreitol, a second sulfhydryl reducing
      agent, also markedly prevented wortmannin-induced inhibition of PI3K. These
      results indicate that the wortmannin-induced inhibition of PI3K is markedly
      prevented by millimolar concentrations of sulfhydryl reducing agents such as 2
      mercaptoethanol and dithiothreitol in the medium, presumably by the binding of
      wortmannin to the agents.

PMID- 21857085
TI  - Effects of angiotensin-converting enzyme inhibitors beyond lowering blood
      pressure--are they important for doctors?
AB  - Large clinical trials and experimental studies have indicated that not all of the
      beneficial properties of angiotensin-converting enzyme inhibitors (ACE-Is) can be
      attributed to the lowering of blood pressure. The aim of this study was to assess
      doctors' opinions about the importance of the cardioprotective effects of ACE-Is
      beyond lowering blood pressure. The study participants (685 physicians) filled in
      a questionnaire testing doctors' knowledge of all of the therapeutic effects of
      ACE-Is not directly associated with lowering blood pressure and their clinical
      importance. In addition, each doctor filled in 20 questionnaires for subsequent
      patients treated with any ACE-I. Fifty-nine percent of the investigated
      physicians were aware of most of the therapeutic effects of ACE-Is. The most
      important therapeutic effects for the respondents were the following: reduction
      of peripheral resistance, inhibition of left ventricle hypertrophy, inhibition of
      vascular remodeling and atherosclerotic plaque stabilization. The most commonly
      prescribed ACE-Is were perindopril, lisinopril and chinalapril for inhibition of
      left ventricular hypertrophy and perindopril, ramipril and chinalapril for
      inhibition of arterial wall remodeling. The ACE-Is that were used to reduce
      peripheral vessel resistance included perindopril, lisinopril and trandolapril.
      Drugs used to stabilize the plaque included perindopril, lisinopril and
      cilazapril. The therapeutic effects of ACE-Is beyond lowering blood pressure were
      considered to be valid and important in daily clinical practice for the
      prevention of cardiovascular diseases and diabetic complications. The attribution
      of the effects of a particular ACE-I was not always in accordance with evidence
      based medicine. The obtained treatment outcomes were attributed to the entire
      group of ACE-Is.

PMID- 21857086
TI  - Administration of L-carnitine and mildronate improves endothelial function and
      decreases mortality in hypertensive Dahl rats.
AB  - Hypertension is a well established risk factor for the development of
      cardiovascular diseases and increased mortality. This study was performed to
      investigate the effects of the administration of L-carnitine or mildronate, an
      inhibitor of L-carnitine biosynthesis, or their combination on the development of
      hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a
      high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7
      weeks of age. Experimental animals were divided into five groups and treated for
      8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate
      (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at the doses
      above (n = 10). During the experiment, control group animals continued to consume
      a diet with normal salt content. Administration of the combination significantly
      improved the survival rate for 50% of the population. None of the tested
      compounds or their combination influenced high salt intake-induced hypertension,
      while treatment with mildronate and the combination for 8 weeks significantly
      decreased resting heart rate by 12% and 10%, respectively. Feeding with high salt
      diet had no influence on systolic function of the heart, but it induced
      thickening of the ventricular walls and development of heart hypertrophy that was
      not improved by the administration of tested compounds. In addition,
      administration of the combination attenuated the development of endothelial
      dysfunction in isolated aortic rings. In conclusion, our results demonstrate that
      treatment with a combination of L-carnitine and mildronate is protective against
      hypertension-induced complications in an experimental model of salt-induced
      hypertension.

PMID- 21857087
TI  - Hemostatic effects of bezafibrate and omega-3 fatty acids in isolated
      hypertriglyceridemic patients.
AB  - This study aimed to compare the effects of omega-3 fatty acids and fibrate
      treatment on plasma levels and activities of hemostatic risk factors on glucose
      and lipid metabolism in subjects with isolated hypertriglyceridemia. Seventy
      three subjects with elevated triglyceride levels were allocated into one of the
      following treatment options: bezafibrate (200 mg twice daily), omega-3 fatty
      acids (1 g twice daily) or placebo. Plasma lipids, glucose homeostasis markers
      (fasting and 2-h post-glucose load plasma glucose levels and HOMA), as well as
      plasma levels/activities of fibrinogen, factor VII and PAI-1 were determined at
      baseline, on the day of randomization, and after 4 and 12 weeks of the treatment.
      Not only did bezafibrate improve plasma lipids, but it also increased glucose
      sensitivity and tended to reduce post-glucose loads of plasma glucose. Except for
      the reduction in plasma triglycerides, omega-3 fatty acids produced no effect on
      the lipid profile and insulin sensitivity. Both treatment options reduced, to
      similar extents, plasma levels of fibrinogen and PAI-1 and factor VII coagulant
      activity. Our study indicates that, although fibrates exhibit more-pronounced
      metabolic effects than do omega-3 fatty acids, both these treatment options are
      equipotent in producing a complex beneficial effect on hemostasis in isolated
      hypertriglyceridemic subjects.

PMID- 21857088
TI  - N-phenylmaleimide derivatives as mimetic agents of the pro-inflammatory process:
      myeloperoxidase activation.
AB  - Myeloperoxidase (MPO) is an important enzyme that catalyzes the reaction between
      hydrogen peroxide and chloride to generate hypochlorous acid, which oxidizes a
      range of biomolecules and has been associated with inflammatory diseases. The
      synthetic compounds N-phenylmaleimide (NFM) and 4-methyl-N-phenylmaleimide (Me
      NFM) increased the MPO activity in vitro (of isolated enzyme and in isolated
      cells after animal treatment) and in vivo assays. MPO-induction may represent a
      good model system to investigate the molecular and cellular mechanisms of
      oxidative cell injury induced by activated neutrophils, and the interactions
      between damaging species involved in the respiratory burst.

PMID- 21857089
TI  - Puerarin inhibits iNOS, COX-2 and CRP expression via suppression of NF-kappaB
      activation in LPS-induced RAW264.7 macrophage cells.
AB  - Puerarin (7,4'-dihydroxy-8-C-glucosylisoflavone) is the most abundant isoflavone
      C-glucoside extracted from Radix puerariae, and it has been used for various
      medicinal purposes in traditional oriental medicine for thousands of years. In
      the present study, the ability of the puerarin to modulate inducible nitric oxide
      synthase (iNOS), cyclooxygenase-2 (COX-2) and C reactive protein (CRP) expression
      and induce changes in the nuclear factor kappaB (NF-kappaB) pathway in RAW264.7
      macrophage cells was examined. The protein and mRNA levels of lipopolysaccharide
      (LPS)-induced iNOS, COX-2 and CRP were determined in RAW246.7 macrophage cells.
      Inhibitor kappaB (I-kappaB) phosphorylation and p65NF-kappaB expression in
      RAW246.7 macrophage cells were also detected under our experimental conditions.
      The results indicated that puerarin inhibited the expression of LPS-induced iNOS,
      COX-2 and CRP proteins and also suppressed their mRNAs from RT-PCR experiments in
      RAW264.7 cells. Subsequently, we determined that the inhibition of iNOS, COX-2
      and CRP expression was due to a dose-dependent inhibition of phosphorylation and
      degradation of I-kappaB, which resulted in the reduction of p65NF-kappaB nuclear
      translocation. These data suggested that the effect of puerarin-mediated
      inhibition of LPS-induced iNOS, COX-2 and CRP expression is attributed to
      suppressed NF-kappaB activation at the transcriptional level.

PMID- 21857090
TI  - Naturally appearing N-feruloylserotonin isomers suppress oxidative burst of human
      neutrophils at the protein kinase C level.
AB  - N-feruloylserotonin (N-f-5HT) isomers, isolated from seeds of Leuzea carthamoides
      (Wild) DC, inhibited dose-dependent oxidative burst in human whole blood and
      isolated neutrophils in vitro, which were measured by luminol- and/or isoluminol
      enhanced chemiluminescence in the following rank order of stimuli: PMA > OpZ >
      calcium ionophore A23187. In isolated neutrophils that were stimulated with PMA,
      N-f-5HT isomers were effective against extracellular and intracellular reactive
      oxygen species. Liberation of ATP, analysis of apoptosis, and recombinant caspase
      3 activity revealed that N-f-5HT isomers, used in concentrations up to 100 MUM,
      did not alter the viability and integrity of isolated neutrophils. Western blot
      analysis documented that in concentrations of 10 and 100 MUM, N-f-5HT isomers
      significantly decreased PMA-induced phosphorylation of PKC alpha/beta II. The
      results suggest that N-f-5HT isomers are an effective, naturally occurring
      substance with a potent pharmacological effect on the oxidative burst of human
      neutrophils. It should be further investigated for its pharmacological activity
      against oxidative stress in ischemia-reperfusion, inflammation and other
      pathological conditions.

PMID- 21857091
TI  - Primary and secondary clarithromycin, metronidazole, amoxicillin and levofloxacin
      resistance to Helicobacter pylori in southern Poland.
AB  - The aim of this study was to assess the primary and secondary resistance of H.
      pylori strains cultured from adult patients of the Malopolska region of Poland,
      mainly of Krakow and the surrounding areas, to antibacterial agents (amoxicillin,
      clarithromycin, metronidazole and levofloxacin). In total, 115 H. pylori strains
      were isolated, of which 90 strains originated from patients who had never been
      treated for H. pylori infection, while the remaining 25 were isolated from
      patients in whom eradication of the infection failed after treatment. All tested
      H. pylori strains were susceptible to amoxicillin. Forty-four percent of strains
      isolated were resistant to metronidazole. The primary and secondary resistance to
      this antimicrobial chemotherapeutic reached 37% and 72% (p = 0.002),
      respectively. In total, 34% of strains were resistant to clarithromycin, and the
      ratio of strains with secondary resistance was significantly greater than that of
      the strains with primary resistance (80% vs. 21%, p < 0.001). The double
      resistance to both metronidazole and clarithromycin was confirmed in 23% of H.
      pylori strains. Five percent of H. pylori strains were resistant to levofloxacin,
      while primary and secondary resistance to this drug accounted for 2% and 16% (p =
      0.006), respectively. In total, 4% of H. pylori strains were simultaneously
      resistant to metronidazole, clarithromycin and levofloxacin. Thus, the high
      resistance to metronidazole and clarithromycin excludes the possibility of using
      these drugs for treatment of H. pylori infection without earlier antibiogramming.
      Levofloxacin, as a drug of high efficacy against H. pylori, should be reserved
      for an "emergency" therapy and used in a limited capacity in order to preserve
      its potent antimicrobial activity. The Polish Society of Gastroenterology
      recommends levofloxacin as a third-line therapy.

PMID- 21857092
TI  - Frequency of the C1236T, G2677T/A and C3435T MDR1 gene polymorphisms in the
      Serbian population.
AB  - The multi-drug resistance 1 (MDR1) gene encodes for a P-glycoprotein (PGP), which
      acts as a gate-keeper against various kinds of xenobiotics. Several single
      nucleotide polymorphisms (SNPs) in the MDR1 gene that may influence PGP level and
      function have been identified. The aim of this study was to simultaneously
      analyze the three most important MDR1 SNPs, C3435T, G2677T/A and C1236T, in the
      Serbian population and to compare the results with those published for other
      ethnic groups. A group of 158 unrelated, healthy subjects was included in the
      present study. For determination of MDR1 SNPs, a multiplexed mutagenically
      separated PCR was performed. The genotype frequency of the analyzed MDR1 SNPs was
      as follows: 3435 nt - 0.19 (CC), 0.54 (CT) and 0.27 (TT); 2677 nt - 0.26 (GG),
      0.52 (GT), 0.15 (TT), 0.03 (GA) and 0.064 (TA), and 1236 nt - 0.23 (CC), 0.61
      (CT) and 0.16 (TT). Our results for the Serbian population could be relevant for
      further investigation of drugs that are substrates of PGPand for studies of
      interethnic diversity in MDR1 polymorphism frequency.

PMID- 21857093
TI  - Influence of ABCB1, CYP3A4*18B and CYP3A5*3 polymorphisms on cyclosporine A
      pharmacokinetics in bone marrow transplant recipients.
AB  - The aim of this study was to retrospectively evaluate the effect of polymorphisms
      in the CYP3A4, CYP3A5 and ABCB1 genes on the dose-adjusted concentration and dose
      requirement of cyclosporine A(CsA) in Chinese recipients during the early period
      after bone marrow or hematopoietic stem cell transplantation. Ninety-one bone
      marrow transplant recipients were genotyped by the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) assay or by direct sequencing
      for the C1236T, G2677T/A and C3435T polymorphisms in CYP3A4*18B, CYP3A5*3, and
      ABCB1, respectively. The concentration at zero before administration (C0) and
      concentration at 2 h after administration (C2) of whole blood CsA were measured
      by fluorescence polarization immunoassay. Dose-adjusted C0 and C2 were determined
      and compared among groups with different genotypes. Compared with CYP3A5*3/*3
      individuals, CYP3A5*1/*1 subjects have a significantly lower dose-adjusted C0 and
      C2 at days 1-10 and a higher dose requirement for CsA at days 16-30 (p < 0.05).
      In addition, homozygotes for the ABCB1 3435T mutant have a significantly higher
      dose-adjusted C0 and C2 and a lower dose requirement compared with wildtype (p <
      0.05). Similar results were also derived for carriers of the T-G-C haplotype in
      CYP3A5 producers compared with non-carriers (p < 0.05 and p < 0.01,
      respectively). In summary, the ABCB1 3435T SNP, T-G-C haplotype in CYP3A5
      producers, and CYP3A5*3 SNP are all associated with differences in CsA
      pharmacokinetics and dose requirements during the first month after bone marrow
      or hematopoietic stem cell transplantation. Genetic testing can therefore help to
      determine initial dosage and individualize immunosuppressive therapy.

PMID- 21857094
TI  - Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with
      posttransplant diabetes mellitus in kidney transplant patients medicated with
      tacrolimus.
AB  - New onset posttransplant diabetes mellitus (PTDM) has a high incidence after
      kidney transplantation in patients medicated with tacrolimus. PTDM can adversely
      affect patient and graft survival. The pathophysiology of PTDM closely mimics
      type 2 diabetes mellitus (T2DM). One of the possible genetic factors predisposing
      individuals to PTDM might be a polymorphism in the transcription factor 7-like 2
      gene (TCF7L2). This polymorphism has previously been associated with increased
      risk of T2DM in the general population. Therefore, the present study aimed to
      evaluate TCF7L2 polymorphisms in PTDM in kidney transplant patients medicated
      with tacrolimus. Non-diabetic kidney transplant patients medicated with
      tacrolimus (n = 234) were genotyped for the presence of TCF7L2 gene variants
      (rs12255372 and rs7903146) using TaqMan probes. Of the 234 patients, 66 patients
      had developed PTDM and 168 had not. Frequencies of the studied single nucleotide
      polymorphisms (SNPs) did not differ significantly between the study groups.
      Moreover, haplotype analyses failed to detect any associations between TCF7L2
      haplotypes and PTDM. However, in late-onset PTDM (developed later that 2 weeks
      from transplantation), frequencies of the rs7903146 TT genotype and T minor
      allele were significantly increased compared to non-PTDM controls (17.9% vs.
      5.9%, p = 0.017, OR: 4.13, 95% CI: 1.19-14.33 for TT genotype, 39.3% vs. 25.9%, p
      = 0.038 for T allele). If the application of TCF7L2 rs7903146 SNPs as a marker
      for PTDM is confirmed by further independent studies, replacing tacrolimus with
      other immunosuppressants could be warranted in patients at high risk of PTDM, as
      diagnosed by TCF7L2 genotyping.

PMID- 21857095
TI  - N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in
      the forced swim test and the tail suspension test in mice.
AB  - The antidepressant-like effects of N-palmitoylethanolamide (PEA), a putative
      endocannabinoid, was investigated in mice using the tail suspension test (TST)
      and the forced swimming test (FST). In TST, PEA (10, 20, and 40 mg/kg) produced a
      statistically significant reduction in immobility (50, 32, and 34%, respectively,
      vs. the control group), whereas fluoxetine (20 mg/kg) reduced immobility by 38%.
      In FST, PEA (5, 10, and 20 mg/kg) produced a statistically significant reduction
      in immobility (15, 21, and 36%, respectively), whereas fluoxetine (20 mg/kg)
      reduced immobility by 18%. Moreover, PEA (20 mg/kg) did not significantly change
      motor activity in a spontaneous behavioral test. In conclusion, PEA (dose range
      of 5-40 mg/kg) administered orally reduced immobility in TST and FST, comparable
      to the antidepressant effect of fluoxetine, and had no effect on spontaneous
      activity in mice.

PMID- 21857096
TI  - Effect of neuraminidase treatment on persistent epileptiform activity in the rat
      hippocampus.
AB  - Negatively charged sialic acid residues located close to pores of voltage-gated
      sodium channels substantially influence their gating properties. The in vitro low
      Mg2+ seizure model is used to emulate difficult-to-treat status epilepticus.
      Using this model on cultured hippocampal slices, we examined the effectiveness of
      desialylation in reducing persistent seizure-like activity. We show that
      desialylation in cultured hippocampal slices effectively suppresses seizure-like
      activity induced by low Mg2+. These findings suggest that targeting negatively
      charged sialic acids may be an effective strategy to treat status epilepticus.

PMID- 21857097
TI  - Electronic structure and luminescence mechanisms in ZnMoO4 crystals.
AB  - Calculations of the band structure, partial densities of states and optical
      spectra of permittivity, reflectivity and absorption of perfect ZnMoO(4) crystal
      were performed using the full-potential linear-augmented-plane-wave method. It is
      shown that the calculated reflectivity spectra reproduce the main features of
      corresponding experimental spectra in the fundamental absorption region. The
      bandgap value of ZnMoO(4) is estimated as E(g) = 4.3 eV. Peculiarities of
      luminescence excitation spectra corrected for near-surface losses and losses on
      reflectivity are discussed, taking into account the results of the calculations.
      It is found that the energy structure of the lower part of conduction band is
      manifested in the excitation spectra of the intrinsic luminescence. The
      excitation spectra in the region 4.3-8.0 eV are formed by band-to-band electronic
      transitions mainly within the molybdate groups MoO(4)(2-), whereas electronic
      states of Zn(2+) cations are not directly involved into the excitation processes.
      It is shown that the structure of the intrinsic luminescence excitation spectrum
      depends on the temperature and mechanisms of the structure modification are
      discussed.

PMID- 21857098
TI  - The thermoelectric power factor of a semiconductor superlattice with nanoparticle
      inclusions.
AB  - We develop a phenomenological theory for cross-plane transport in a semiconductor
      superlattice (SL) doped with nanostructures to improve the thermoelectric
      properties. The SL consists of an array of quantum wells equally spaced along a
      spatial direction separated by narrow barriers, such that, in the presence of
      inter-well tunneling, a miniband energy structure is established. The semi
      metallic ErAs nanoparticles are embedded inside the quantum wells in the process
      of growth of the SL, as reported in several recent experiments. Their effect on
      thermoelectric transport is considered through an additional contribution to the
      electron scattering rate, that is correlated with a process of resonant tunneling
      through the nanoparticle-semiconductor interface modeled as a Schottky barrier.
      In a semi-classical approximation of the miniband conduction regime, we calculate
      the electric conductivity, the thermopower and the power factor as a function of
      the barrier height and demonstrate the presence of a filtering effect, whereby
      the Seebeck coefficient is enhanced by the additional scattering.

PMID- 21857099
TI  - Metallization and investigation of electrical properties of in vitro
      recrystallized mSbsC-eGFP assemblies.
AB  - Surface layer (SL) proteins are self-assembling nanosized arrays which can be
      recrystallized in solution or on surfaces. In this paper, we investigate the
      metallization, contact potential difference and conductivity of in vitro
      recrystallized mSbsC-eGFP tube-like assemblies for possible applications in
      nanobiotechnology. Treatment of mSbsC-eGFP tube-like structures with 150 mM Pt
      salt solution resulted in the formation of metallized SL assemblies decorated
      with Pt nanoparticles (? > 3 nm) which were closely packed and aggregated into
      metal clusters. Kelvin probe force microscopy (KPFM) measurements revealed that
      metallized and unmetallized SL templates showed different surface potential
      behaviours, demonstrating that the metal coating changes the electrostatic
      surface characteristics of SL assemblies. In situ conductivity measurements
      showed that unmetallized SL assemblies were not conductive. Metallized samples
      showed linear I-V dependence between - 1 and + 1 V with a conductivity of ~ 10(3)
      S m( - 1).

PMID- 21857100
TI  - Phosphorus atomic layer doping of germanium by the stacking of multiple delta
      layers.
AB  - In this paper we demonstrate the fabrication of multiple, narrow, and closely
      spaced delta-doped P layers in Ge. The P profiles are obtained by repeated
      phosphine adsorption onto atomically flat Ge(001) surfaces and subsequent thermal
      incorporation of P into the lattice. A dual-temperature epitaxial Ge overgrowth
      separates the layers, minimizing dopant redistribution and guaranteeing an
      atomically flat starting surface for each doping cycle. This technique allows P
      atomic layer doping in Ge and can be scaled up to an arbitrary number of doped
      layers maintaining atomic level control of the interface. Low sheet resistivities
      (280 Omega/ [symbol see text ) and high carrier densities (2 * 10(14) cm( - 2),
      corresponding to 7.4 * 10(19) cm( - 3)) are demonstrated at 4.2 K.

PMID- 21857101
TI  - Controversy over the report on a bacterium that feeds on arsenic.

PMID- 21857102
TI  - Helminth richness in Arunachal Pradesh fishes: a forgotten component of
      biodiversity.

PMID- 21857103
TI  - Jeewanu, or the 'particles of life'. The approach of Krishna Bahadur in 20th
      century origin of life research.
AB  - Starting in the 1960s, the Indian chemist Krishna Bahadur, from the University of
      Allahabad, published on organic and inorganic particles that he had synthesized
      and baptized 'Jeewanu', or 'particle of life'. Bahadur conceived of the Jeewanu
      as a simple form of the living. These studies are presented in a historical
      perspective and positioned within mid-20th century research on the origin of
      life, notably the so-called 'coacervate theory' of the Soviet biochemist
      Aleksandr I Oparin. The concepts of life proposed by Bahadur, Oparin and others
      are discussed from a historical standpoint.

PMID- 21857104
TI  - What history tells us XXV. Construction of the ribbon model of proteins (1981).
      The contribution of Jane Richardson.

PMID- 21857105
TI  - Adaptation or exaptation? The case of the human hand.
AB  - A controversy of relevance to the study of biological form involves the concept
      of adaptation. This controversy is illustrated by the structure and function of
      the human hand. A review of the principal definitions of adaptation points to two
      main problems: (1) they are qualitative and make reference to the whole structure
      (or substructural feature) and (2) they are based on the idea of natural
      selection as a moulding factor. The first problem would be solved by a definition
      that encompasses quantitative measures of the effects of selection, drawing on
      new advances in the comparative method. The second problem is deeper and presents
      greater conceptual difficulties. I will argue that the idea of natural selection
      as a moulding factor depends on the notion of a genetic program for development.
      But regarding the hand, experimental evidence on limb development challenges the
      idea of a genetic program for skeletal pattern formation, undermining a simple
      application of standard adaptationist concepts. These considerations lead to a
      revised definition of adaptation and interpretation of the evolutionary
      determinants of the hand's form.

PMID- 21857106
TI  - Analysis of phage Mu DNA transposition by whole-genome Escherichia coli tiling
      arrays reveals a complex relationship to distribution of target selection protein
      B, transcription and chromosome architectural elements.
AB  - Of all known transposable elements, phage Mu exhibits the highest transposition
      efficiency and the lowest target specificity. In vitro, MuB protein is
      responsible for target choice. In this work, we provide a comprehensive
      assessment of the genome-wide distribution of MuB and its relationship to Mu
      target selection using high-resolution Escherichia coli tiling DNA arrays. We
      have also assessed how MuB binding and Mu transposition are influenced by
      chromosome-organizing elements such as AT-rich DNA signatures, or the binding of
      the nucleoid-associated protein Fis, or processes such as transcription. The
      results confirm and extend previous biochemical and lower resolution in vivo
      data. Despite the generally random nature of Mu transposition and MuB binding,
      there were hot and cold insertion sites and MuB binding sites in the genome, and
      differences between the hottest and coldest sites were large. The new data also
      suggest that MuB distribution and subsequent Mu integration is responsive to DNA
      sequences that contribute to the structural organization of the chromosome.

PMID- 21857107
TI  - RET gene mutations and polymorphisms in medullary thyroid carcinomas in Indian
      patients.
AB  - Germline mutations of RET gene are pathognomonic of multiple endocrine neoplasia
      (MEN; MEN 2A/MEN 2B) and familial medullary thyroid carcinoma (FMTC),
      constituting 25% of medullary thyroid carcinomas (MTCs). We investigated RET gene
      mutations and polymorphisms at exons 10, 11, 13, 14, 15 and 16 in 140 samples,
      comprising 51 clinically diagnosed MTC patients, 39 family members of patients
      and 50 normal individuals. The method of choice was PCR and direct nucleotide
      sequencing of the PCR products. RET gene mutations were detected in 15 (29.4%)
      patients, with MEN 2A/FMTC in 13 patients and MEN 2B in 2 patients. Further, 39
      family members of seven index cases were analysed, wherein four of the seven
      index cases showed identical mutations, in 13 of 25 family members. We also
      examined single nucleotide polymorphisms (SNPs) in RET gene exons in 101
      unrelated samples. Significant differences in the allelic frequencies of SNPs at
      codons 691, 769, 836 and 904 between patient and control groups were not
      observed. However, SNP frequencies were significantly different in the Indian
      group as compared with other European groups. We identified two novel, rare and
      unique SNPs separately in single patients. Our study demonstrated presence of MEN
      2A/MEN 2B/FMTC-associated mutations in accordance with the reported literature.
      Thus, RET gene mutations in exons 10, 11, 13, 14, 15 and 16 constitute a rapid
      test to confirm diagnosis and assess risk of the disease in familial MEN 2A/MEN
      2B/FMTC.

PMID- 21857108
TI  - Transgene transmission in chickens by sperm-mediated gene transfer after seminal
      plasma removal and exogenous DNA treated with dimethylsulfoxide or N,N
      dimethylacetamide.
AB  - Transgenic animals have been successfully produced by mass gene transfer
      techniques such as sperm-mediated gene transfer (SMGT). The aim of this work was
      to demonstrate transgene transmission by SMGT in chickens using dimethylsulfoxide
      (DMSO) or N,N-dimethylacetamide (DMAc) as transfectants after seminal plasma
      removal to prevent DNase activity. Sperm samples were prepared by repetitive
      washes, and after each wash sperm motility, seminal plasma proteins, exogenous
      DNA integrity and its uptake by spermatozoa were evaluated. Laying hens were
      inseminated using spermatozoa transfected with pEGFP-N1 vector in the presence of
      DMSO or DMAc. Transgene transmission in newborn chicks was evaluated by in vivo
      enhanced green fluorescent protein (EGFP) expression, RT-PCR and PCR analysis.
      DNA internalization was limited to sperm samples washed twice. The presence of
      DMSO or DMAc during transfection had no effect on fertilization or hatching
      rates. PCR analysis detected the presence of EGFP DNA in 38% of newborn chicks
      from the DMSO group and 19% from the DMAc group. EGFP mRNA was detected in 21% of
      newborn chicks from the DMSO group, as against 8.5% from the DMAc group. However,
      in vivo expression of EGFP was only observed in a single animal from the DMSO
      group. Our data revealed that the plasmid DNA-DMSO combination coupled with sperm
      washes can be an efficient method for transfection in chickens.

PMID- 21857109
TI  - The regulatory epicenter of miRNAs.
AB  - miRNAs are small non-coding RNAs with average length of ~21 bp. miRNA formation
      seems to be dependent upon multiple factors besides Drosha and Dicer, in a
      tissue/stage-specific manner, with interplay of several specific binding factors.
      In the present study, we have investigated transcription factor binding sites in
      and around the genomic sequences of precursor miRNAs and RNA-binding protein
      (RBP) sites in miRNA precursor sequences, analysed and tested in comprehensive
      manner. Here, we report that miRNA precursor regions are positionally enriched
      for binding of transcription factors as well as RBPs around the 3' end of mature
      miRNA region in 5' arm. The pattern and distribution of such regulatory sites
      appears to be a characteristic of precursor miRNA sequences when compared with
      non-miRNA sequences as negative dataset and tested statistically.When compared
      with 1 kb upstreamregions, a sudden sharp peak for binding sites arises in the
      enriched zone near the mature miRNA region. An expression-data-based correlation
      analysis was performed between such miRNAs and their corresponding transcription
      factors and RBPs for this region. Some specific groups of binding factors and
      associated miRNAs were identified. We also identified some of the overrepresented
      transcription factors and associated miRNAs with high expression correlation
      values which could be useful in cancer-related studies. The highly correlated
      groups were found to host experimentally validated composite regulatory modules,
      in which Lmo2-GATA1 appeared as the predominant one. For many of RBP-miRNAs
      associations, coexpression similarity was also evident among the associated miRNA
      common to given RBPs, supporting the Regulon model, suggesting a common role and
      common control of these miRNAs by the associated RBPs. Based on our findings, we
      propose that the observed characteristic distribution of regulatory sites in
      precursor miRNA sequence regions could be critical inmiRNA transcription,
      processing, stability and formation and are important for therapeutic studies.
      Our findings also support the recently proposed theory of self-sufficient mode of
      transcription by miRNAs, which states that miRNA transcription can be carried out
      in host-independent mode too.

PMID- 21857110
TI  - Synergistic growth inhibition of cancer cells harboring the RET/PTC1 oncogene by
      staurosporine and rotenone involves enhanced cell death.
AB  - TPC-1 is a highly proliferative thyroid papillary carcinoma-derived cell line.
      These cells express the RET/PTC1 fusion protein, whose isoforms are characterized
      in this work. The bacterial alkaloid staurosporine and the plant extract rotenone
      are death-inducing drugs that have an inhibitory synergistic effect on the growth
      of TPC-1 cells. We show that this synergism is accompanied by an enhancement of
      the induction of cell death. Staurosporine alone induces cell cycle arrest in G1,
      whereas rotenone induces arrest in G2/M. We suggest that this additive pressure
      may drive cells to die, resulting in the synergistic interaction of the drug
      combination. These data emphasize the potential use of the staurosporine plus
      rotenone combination as an anticancer tool.

PMID- 21857111
TI  - Argonaute-2-null embryonic stem cells are retarded in self-renewal and
      differentiation.
AB  - RNA interference (RNAi) pathways regulate self-renewal and differentiation of
      embryonic stem (ES) cells. Argonaute 2 (Ago2) is a vital component of RNA-induced
      silencing complex (RISC) and the only Ago protein with slicer activity. We
      generated Ago2-deficient ES cells by conditional gene targeting. Ago2-deficient
      ES cells are defective in the small-RNA-mediated gene silencing and are
      significantly compromised in biogenesis of mature microRNA. The self-renewal rate
      of Ago2-deficient ES cells is affected due to failure of silencing of Cdkn1a by
      EScell- specific microRNAs (miRNA) in the absence of Ago2. Interestingly, unlike
      Dicer- and Dgcr8-deficient ES cells, they differentiate to all three germ layers
      both in vivo and in vitro. However, early differentiation of Ago2-deficient ES
      cells is delayed by 2-4 days as indicated by persistence of higher levels of self
      renewal/ pluripotency markers during differentiation. Further, appearance of
      morphological and differentiation markers is also delayed during the
      differentiation. In this study we show that Ago2 is essential for normal self
      renewal and differentiation. Also, our data suggest that self-renewal and
      differentiation of ES cells are regulated by both siRNA and miRNA pathways.

PMID- 21857112
TI  - Proteomic identification of CIB1 as a potential diagnostic factor in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), among the most common malignancies worldwide,
      remains a major threat to public health, and there is an urgent need to identify
      novel biomarkers for diagnosis, prognosis and targets for anti-cancer treatment.
      In this study, two-dimensional polyacrylamide gel electrophoresis coupled with
      ESI-Q-TOF MS/MS analysis was used to identify differentially expressed proteins
      among the HCC tumour centre, tumour margin and nontumourous liver tissues. In
      total, 52 spots with significant alteration were positively identified
      byMS/MSanalysis. Altered expression of representative proteins, including CIB1,
      was validated by Western blotting. Immunostaining suggested an increase tendency
      of CIB1 expression from nontumourous liver tissue to tumour centre. Knockdown of
      CIB1 expression by RNA interference led to the significant suppression of the
      cell growth in hepatoma HepG2 cells. These data suggest that CIB1 may be used as
      a novel prognostic factor and possibly an attractive therapeutic target for HCC.

PMID- 21857113
TI  - Fourier transform infrared microspectroscopy as a diagnostic tool for
      distinguishing between normal and malignant human gastric tissue.
AB  - Fourier transform infrared (FTIR) microspectroscopy can be considered to be a
      fast and non-invasive tool for distinguishing between normal and cancerous cells
      and tissues without the need for laborious and invasive sampling procedures.
      Gastric samples from four patients (age, 65+/-2 years) were analysed. Samples
      were obtained from the organs removed during gastrectomy and then classified as
      normal or cancerous. Classification was based on histopathological examinations
      at our institution. Formalin-fixed sections of gastric tissue were analysed by
      FTIR-microspectroscopy. To characterize differences between sections of normal
      and cancerous tissue, specific regions of the spectra were analysed to study
      variations in the levels of metabolites. To distinguish between two conditions
      (normal and cancerous), changes in the relative intensity of bands in the range
      600-4000 cm-1 were analysed. A FTIR spectral map of the bands in the region 2800
      3100 cm-1 and 900-1800 cm-1 were created to analyse pathological changes in
      tissues. The limited data available showed that normal gastric tissue had
      stronger absorption than cancerous tissue over a wide region in the four
      patients. There was a significant decrease in total biomolecular components for
      cancerous tissue compared with normal tissue.

PMID- 21857115
TI  - Differences in predatory pressure on terrestrial snails by birds and mammals.
AB  - The evolution of shell polymorphism in terrestrial snails is a classic textbook
      example of the effect of natural selection in which avian and mammalian predation
      represents an important selective force on gene frequency. However, many
      questions about predation remain unclear, especially in the case of mammals. We
      collected 2000 specimens from eight terrestrial gastropod species to investigate
      the predation pressure exerted by birds and mice on snails. We found evidence of
      avian and mammalian predation in 26.5% and 36.8% of the shells. Both birds and
      mammals were selective with respect to snail species, size and morphs. Birds
      preferred the brown-lipped banded snail Cepaea nemoralis (L.) and mice preferred
      the burgundy snail Helix pomatia L. Mice avoided pink mid-banded C. nemoralis and
      preferred brown mid-banded morphs, which were neglected by birds. In contrast to
      mice, birds chose larger individuals. Significant differences in their predatory
      pressure can influence the evolution and maintenance of shell size and
      polymorphism of shell colouration in snails.

PMID- 21857116
TI  - Variation in carbon stocks on different slope aspects in seven major forest types
      of temperate region of Garhwal Himalaya, India.
AB  - The present study was undertaken in seven major forest types of temperate zone
      (1500 m a.s.l. to 3100 m a.s.l.) of Garhwal Himalaya to understand the effect of
      slope aspects on carbon (C) density and make recommendations for forest
      management based on priorities for C conservation/sequestration. We assessed soil
      organic carbon (SOC) density, tree density, biomass and soil organic carbon (SOC)
      on four aspects, viz. north/east (NE), north/west (NW), south-east (SE) and south
      west (SW), in forest stands dominated by Abies pindrow, Cedrus deodara, Pinus
      roxburghii, Cupressus torulosa, Quercus floribunda, Quercus semecarpifolia and
      Quercus leucotrichophora. TCD ranged between 77.3 CMg ha-1 on SE aspect (Quercus
      leucotrichophora forest) and 291.6 CMg ha-1 on NE aspect (moist Cedrus deodara
      forest). SOC varied between 40.3 CMg ha-1 on SW aspect (Himalayan Pinus
      roxburghii forest) and 177.5 CMg ha-1 on NE aspect (moist Cedrus deodara forest).
      Total C density (SOC+TCD) ranged between 118.1 CMg ha-1 on SW aspect (Himalayan
      Pinus roxburghii forest) and 469.1 CMg ha-1 on NE aspect (moist Cedrus deodara
      forest). SOC and TCD were significantly higher on northern aspects as compared
      with southern aspects. It is recommended that for C sequestration, the plantation
      silviculture be exercised on northern aspects, and for C conservation purposes,
      mature forest stands growing on northern aspects be given priority.

PMID- 21857114
TI  - Aggregation properties of a short peptide that mediates amyloid fibril formation
      in model proteins unrelated to disease.
AB  - Short peptides have been identified from amyloidogenic proteins that form amyloid
      fibrils in isolation. The hexapeptide stretch 21DIDLHL26 has been shown to be
      important in the self-assembly of the Src homology 3 (SH3) domain of p85 alpha
      subunit of bovine phosphatidylinositol-3-kinase (PI3-SH3). The SH3 domain of
      chicken brain alpha- spectrin, which is otherwise non-amyloidogenic, is rendered
      amyloidogenic if 22EVTMKK27 is replaced by DIDLHL. In this article, we describe
      the aggregation behaviour of DIDLHL-COOH and DIDLHL-CONH2. Our results indicate
      that DIDLHL-COOH and DIDLHL-CONH2 aggregate to form spherical structures at pH 5
      and 6. At pH 5, in the presence of mica, DIDLHL-CONH2 forms short fibrous
      structures. The presence of NaCl along with mica results in fibrillar structures.
      At pH 6, DIDLHL-CONH2 forms largely spherical aggregates. Both the peptides are
      unstructured in solution but adopt beta-conformation on drying. The aggregates
      formed by DIDLHL-COOH and DIDLHL-CONH2 are formed during drying process and their
      structures are modulated by the presence of mica and salt. Our study suggests
      that a peptide need not have intrinsic amyloidogenic propensity to facilitate the
      selfassembly of the full-length protein. The propensity of peptides to form self
      assembled structures that are nonamyloidogenic could be important in potentiating
      the self-assembly of full-length proteins into amyloid fibrils.

PMID- 21857117
TI  - Eu-Detect: an algorithm for detecting eukaryotic sequences in metagenomic data
      sets.
AB  - Physical partitioning techniques are routinely employed (during sample
      preparation stage) for segregating the prokaryotic and eukaryotic fractions of
      metagenomic samples. In spite of these efforts, several metagenomic studies
      focusing on bacterial and archaeal populations have reported the presence of
      contaminating eukaryotic sequences in metagenomic data sets. Contaminating
      sequences originate not only from genomes of micro-eukaryotic species but also
      from genomes of (higher) eukaryotic host cells. The latter scenario usually
      occurs in the case of host-associated metagenomes. Identification and removal of
      contaminating sequences is important, since these sequences not only impact
      estimates of microbial diversity but also affect the accuracy of several
      downstream analyses. Currently, the computational techniques used for identifying
      contaminating eukaryotic sequences, being alignment based, are slow, inefficient,
      and require huge computing resources. In this article, we present Eu-Detect, an
      alignment-free algorithm that can rapidly identify eukaryotic sequences
      contaminating metagenomic data sets. Validation results indicate that on a
      desktop with modest hardware specifications, the Eu-Detect algorithm is able to
      rapidly segregate DNA sequence fragments of prokaryotic and eukaryotic origin,
      with high sensitivity. A Web server for the Eu-Detect algorithm is available at
      http://metagenomics.atc.tcs.com/Eu-Detect/.

PMID- 21857118
TI  - Genome-based versus gene-based theory of cancer: possible implications for
      clinical practice.
AB  - The current state in oncology research indicates that the attempts to explain
      such complex process as cancerogenesis by a single or several genetic mutations
      were not successful enough. On the other hand, chromosomal/genomic instability-
      almost universal features of malignant tumours which influence a global pattern
      of gene expression and, subsequently, many oncogenic pathways--were often
      disregarded and considered nonessential to clinical application. However, a new
      arising field of system biology including 'new forms' of genome diversity such as
      copy number variations (CNV) and high-throughput oncogene mutation profiling now
      reveal all the complexity of cancer and provide the final explanation of the
      oncogenic pathways, based on stochastic (onco)genomic variation rather than on
      (onco)genic concepts.

PMID- 21857119
TI  - Nucleic acid therapy for lifespan prolongation: present and future.
AB  - Lifespan prolongation is a common desire of the human race. With advances in
      biotechnology, the mechanism of aging has been gradually unraveled, laying the
      theoretical basis of nucleic acid therapy for lifespan prolongation. Regretfully,
      clinically applicable interventions do not exist without the efforts of
      converting theory into action, and it is the latter that has been far from
      adequately addressed at the moment. This was demonstrated by a database search on
      PubMed and Web of Science, from which only seven studies published between 2000
      and 2010 were found to directly touch on the development of nucleic acid therapy
      for anti-aging and/or longevity enhancing purposes. In light of this, the
      objective of this article is to overview the current understanding of the
      intimate association between genes and longevity, and to bring the prospect of
      nucleic acid therapy for lifespan prolongation to light.

PMID- 21857120
TI  - Animal models for the study of arterial hypertension.
AB  - Hypertension is one of the leading causes of disability or death due to stroke,
      heart attack and kidney failure. Because the etiology of essential hypertension
      is not known and may be multifactorial, the use of experimental animal models has
      provided valuable information regarding many aspects of the disease, which
      include etiology, pathophysiology, complications and treatment. The models of
      hypertension are various, and in this review, we provide a brief overview of the
      most widely used animal models, their features and their importance.

PMID- 21857122
TI  - The Rockefeller University Hospital (1910-2010): creating the science of
      medicine.
AB  - The year 2010 marked the centennial of the Rockefeller University Hospital, one
      of the great philanthropic achievements of 20th-century science. For 100 years,
      the Hospital played a central role in the development and growth of medical
      science by enabling physician-scientists to make intensive study of human biology
      and disease. With ingenuity and devotion, they greatly enriched clinical medicine
      as well as basic biological science. This account emphasizes the founding and
      first half-century of the Hospital as it became a germinal center for clinical
      investigation. The second half of the century saw rapid change in medicine and
      health care with vexing problems, many yet unsolved. This history should serve as
      a call to arms for maintaining the linkage of science and medicine, supporting
      patient-oriented research as a basic discipline of medicine.

PMID- 21857121
TI  - Mango ginger (Curcuma amada Roxb.)--a promising spice for phytochemicals and
      biological activities.
AB  - Mango ginger (Curcuma amada Roxb.) is a unique spice having morphological
      resemblance with ginger but imparts a raw mango flavour. The main use of mango
      ginger rhizome is in the manufacture of pickles and culinary preparations.
      Ayurveda and Unani medicinal systems have given much importance to mango ginger
      as an appetizer, alexteric, antipyretic, aphrodisiac, diuretic, emollient,
      expectorant and laxative and to cure biliousness, itching, skin diseases,
      bronchitis, asthma, hiccough and inflammation due to injuries. The biological
      activities of mango ginger include antioxidant activity, antibacterial activity,
      antifungal activity, anti-inflammatory activity, platelet aggregation inhibitory
      activity, cytotoxicity, antiallergic activity, hypotriglyceridemic activity,
      brine-shrimp lethal activity, enterokinase inhibitory activity, CNS depressant
      and analgesic activity. The major chemical components include starch, phenolic
      acids, volatile oils, curcuminoids and terpenoids like difurocumenonol,
      amadannulen and amadaldehyde. This article brings to light the major active
      components present in C. amada along with their biological activities that may be
      important from the pharmacological point of view.

PMID- 21857123
TI  - Compassionate use: a story of ethics and science in the development of a new
      drug.
AB  - This history chronicles the unusual development of the antiviral drug
      ganciclovir. The first compound with activity against human cytomegalovirus
      (CMV), ganciclovir was so clearly efficacious that a placebo-controlled clinical
      trial could not ethically be done, and the FDA rejected the first application to
      market the drug. Used to treat a blinding eye infection in patients with AIDS,
      the story of ganciclovir paralleled the spread of the AIDS epidemic. Both
      ganciclovir and AIDS caught the federal government off guard. Caught in a Catch
      22 situation, the pharmaceutical company developing ganciclovir gave the drug
      away free for five years under compassionate use guidelines. The problems
      encountered in the development of ganciclovir provide guidance on how future
      drugs to treat life-threatening diseases can be developed.

PMID- 21857124
TI  - Is cystic fibrosis genetic medicine's canary?
AB  - In 1989 the gene that causes cystic fibrosis (CF) was identified in a search
      accompanied by intense anticipation that the gene, once discovered, would lead
      rapidly to gene therapy. Many hoped that the disease would effectively disappear.
      Those affected were going to inhale vectors packed with functioning genes, which
      would go immediately to work in the lungs. It was a bewitching image, repeatedly
      invoked in both scientific and popular texts. Gene therapy clinical trials were
      carried out with a range of strategies and occasionally success seemed close, but
      by 1996 the idea that gene therapy for CF would quickly provide a cure was being
      abandoned by the communities engaged with treatment and research. While
      conventional wisdom holds that the death of Jesse Gelsinger in an unrelated gene
      therapy trial in 1999 produced new skepticism about gene therapy, the CF story
      suggests a different trajectory, and some different lessons. This article
      considers the rise and fall of gene therapy for CF and suggests that CF may
      provide a particularly compelling case study of a failed genomic technology,
      perhaps even of a medical "canary." The story of CF might be a kind of warning to
      us that genetic medicine may create as many problems as it solves, and that
      moving forward constructively with these techniques and practices requires many
      kinds of right information, not just about biology, but also about values,
      priorities, market forces, uncertainty, and consumer choice.

PMID- 21857125
TI  - Atavisms: medical, genetic, and evolutionary implications.
AB  - Traits expected to be lost in the evolutionary history of a species occasionally
      reappear apparently out of the blue. Such traits as extra nipples or tails in
      humans, hind limbs in whales, teeth in birds, or wings in wingless stick insects
      remind us that certain genetic information is not completely lost, but can be
      reactivated. Atavisms seem to violate one of the central evolutionary principles,
      known as Dollo's law, that "an organism is unable to return, even partially, to a
      previous stage already realized in the ranks of its ancestors." Although it is
      still not clear what triggers and controls the reactivation of dormant traits,
      atavisms are a challenge to evolutionary biologists and geneticists. This article
      presents some of the more striking examples of atavisms, discusses some of the
      currently controversial issues like human quadrupedalism, and reviews the
      progress made in explaining some of the mechanisms that can lead to atavistic
      features.

PMID- 21857126
TI  - Negotiating meanings about embryos in Australia: from potential humans to
      prohibited substances.
AB  - In the late 1990s, human embryonic stem-cell research became a highly emotional
      and politicized debate. In 2001, the United States announced a ban on all federal
      funding for research involving human embryos, and other countries around the
      world were similarly engaged in political debate at the same time, and for very
      similar reasons--namely, that embryos are regarded as unique entities that
      warrant special protection. This article tracks the transformations in the
      history of legislative response in Australia to the anxieties provoked by the use
      of reproductive and regenerative human material over the last 40 years, in order
      to examine how embryos have come to adopt such a special position in the
      community's psyche. "The embryo" is at once a biological, scientific, social,
      cultural, and political object, fixed by the legislative processes that seek to
      define it, and subject to definitions that change over time. Understanding the
      history of where our ideas about the embryo have come from can help us to
      negotiate the continuing debate about the use of human embryos in research.

PMID- 21857127
TI  - Brain intersections of aesthetics and morals: perspectives from biology,
      neuroscience, and evolution.
AB  - For centuries, only philosophers debated the relationship between aesthetics and
      morality. Recently, with advances in neuroscience, the debate has moved to
      include the brain and an evolved neural underpinning linking aesthetic reactions
      and moral judgment. Biological survival emphasizes mate selection strategies, and
      the ritual displays have been linked to human aesthetics in the arts, in faces,
      and in various daily decision making. In parallel, cultural human practices have
      evolved to emphasize altruism and morality. This article explores the biological
      background and discusses the neuroscientific evidence for shared brain pathways
      for aesthetics and morals.

PMID- 21857128
TI  - "Wonders unconceived": reflections on the birth of medical entomology.
AB  - Prior to Patrick Manson's discovery in 1877 that the mosquito Culex fatigans was
      the intermediate host of filariasis, the association of insects with disease and
      the nature of disease transmission was almost entirely speculation. Manson's work
      was incomplete, however, because it showed the manner in which the mosquito
      acquired the infection from humans, but failed to show the way in which the
      mosquito passed the infection to humans. That pathogens were transmitted by the
      bite of an infected female mosquito was later proven experimentally with bird
      malaria by Manson's protege, Ronald Ross. In 1898 Ross demonstrated that the
      infective stage of the malarial parasite was injected into the host when the
      mosquito released saliva into the wound prior to injesting blood. Insects were
      suspected as carriers of disease for centuries, yet it was not until the late
      1870s that the uncritical acceptance of folk beliefs was supplanted by research
      based scientific medicine. Why did it take so long? The answer lies in the fact
      that early medicine itself was imprecise and could not have pursued the subject
      with any hope of useful results until the last quarter of the 19th century. A
      better understanding of the nature of the disease process (germ theory of
      disease) and improved technology (microscopes and oil-immersion lenses with
      greater resolving power, and synthetic tissue stains) were indispensable for
      revealing the nexus between those partners in crime: insects and parasites.

PMID- 21857129
TI  - The two (institutional) cultures: a consideration of structural barriers to
      interdisciplinarity.
AB  - C. P. Snow's famous Two Cultures essay has become a foil for decades of
      discussions over the relation between science and the humanities. The problem of
      the "two cultures" is often framed in terms of how the particular epistemological
      claims or general intellectual orientations of particular individuals on either
      side of this purported divide obstruct interdisciplinary dialogue or cooperation.
      This formulation, however, fails to consider the institutional frameworks within
      which such debates occur. This article examines the broader structural
      constraints that provide incentives, erect barriers, or otherwise shape the
      potential for interdisciplinary research and practice, with particular attention
      to work involving the life sciences. It argues that in order to understand the
      nature and scope of the problems facing interdisciplinary work, we must focus on
      the institutional constraints that shape how individuals frame questions, pursue
      investigations, develop careers, and collaborate.

PMID- 21857130
TI  - Conceiving wholeness: women, motherhood, and ovarian transplantation, 1902 and
      2004.
AB  - Scholars have shown that organ transplantation may transform ideas about one's
      body, with recipients feeling that they are receiving not just a body part but
      also a part of the donor's identity. This article focuses on a different way in
      which organ transplantation shapes recipient identity: the idea of becoming
      whole. We present the case studies of two women separated by a century (one in
      1902 and the other in 2004) who sought ovarian transplantation, and examine how
      ovarian transplantation can engender a sense of wholeness on the individual, the
      familial, and the cultural levels, due to its ability to enable a recipient to
      naturally conceive and experience pregnancy.

PMID- 21857131
TI  - Preface. Pandemic influenza: emergency response reaching the beloved community.

PMID- 21857132
TI  - Respecting and protecting the beloved community, especially susceptible and
      vulnerable populations.

PMID- 21857133
TI  - Emergency preparedness for a pandemic influenza: ethical challenges for black
      ministers and the public health community.

PMID- 21857134
TI  - Preparing for an influenza pandemic: are some people more equal than others?
AB  - CONTEXT: Planning for a severe influenza pandemic entails facing many substantive
      public health challenges, especially in the area of the distribution of
      insufficient supplies of materials and personnel. It is anticipated that
      rationing of health care resources will be required, thus demanding that choices
      be made about which individuals should receive potentially life-saving care when
      not all who can be saved can be served. EVIDENCE ACQUISITION: Most proposed
      triage and allocation plans have used medical inclusion and exclusion criteria to
      reduce this gap, but there will still be many more patients than resources. Thus,
      the potential to arbitrarily exclude groups of people on non-medical grounds in
      order to reduce relative scarcity could offer an attractive option. Can societies
      make reasoned anticipatory decisions to keep certain people from receiving
      influenza treatment in order to maximize the availability of care for other, more
      favored groups? RESULTS: In this paper, we argue that taking the fundamental
      moral equality of people seriously requires the inclusion of vulnerable, socially
      marginalized groups (such as illegal immigrants and incarcerated prisoners) in
      planning for a pandemic. While there may be a majoritarian justification for a
      priori discrimination against some groups of people on non-medical grounds, there
      are no morally defensible reasons to do so and many reasons not to engage in such
      behavior. CONCLUSIONS: Pandemic planners should resist attempts to institute
      either unsanctioned or authorized discrimination in resource allocation. Because
      of their unique position in society, their ethical code and their essential role
      in confronting a pandemic, physicians can (and should) defend egalitarianism in
      the allocation of health care resources in such a public health crisis and
      advocate and act against such exclusion were it to occur.

PMID- 21857135
TI  - The impact of disparities in health on pandemic preparedness.

PMID- 21857136
TI  - Hindsight, irony, and the ethical: a commentary on pandemics, social distancing,
      and community mitigation strategies involving African American clergy.

PMID- 21857137
TI  - Local public health responses to the threat of pandemic flu: equitable protection
      and communities at disproportionate risk.

PMID- 21857138
TI  - Story telling and managing trauma: health and spirituality at work.
AB  - This article presents a narrative or story-telling approach to managing trauma.
      The emphasis is on helping religious and spiritual caregivers, as first
      responders, to manage the impact of trauma on victims as well as on their own
      lives as caregivers. Religious and spiritual caregivers come from a wide range of
      traditions, including the Judeo-Christian and Muslim faiths and self-help
      frameworks that draw on creation spirituality. The aims of this presentation are
      (1) to define trauma, (2) to review the literature supporting evidenced-based
      trauma intervention and its importance to narrative intervention, (3) to examine
      the impact that trauma has on first responders, and (4) to present a narrative or
      story-telling model of managing the impact that trauma has on the lives of those
      suffering from traumatic events as well as the impact of trauma on the lives of
      religious and spiritual caregivers.

PMID- 21857139
TI  - Preparing for an influenza pandemic: policy implications for rural Latino
      populations.
AB  - Abstract:The purpose of this study was to assess influenza preparedness levels
      among Spanish-speaking adults ages 18 and older in two rural communities in
      Central California. Data were collected from 209 participants using the 21-item
      Emergency Preparedness Measurement Scale, an instrument designed and validated
      for this study. Results suggest that adult Spanish-speaking Latinos are not
      prepared for a pandemic influenza regardless of their gender, age, number of
      years living in the United States, education, or income level. Furthermore, study
      participants cited lack of insurance, limited knowledge about needed emergency
      supplies, and preference for fresh foods as reasons for lacking emergency
      supplies at home.

PMID- 21857140
TI  - Pandemic influenza conference: discussion and conclusion.

PMID- 21857141
TI  - Conventional aortic valve replacement for elderly patients in the current era.
AB  - BACKGROUND: Because of the rising expectation of prolonged life in the general
      population and the recent recognition of undertreated aortic valve disease in the
      elderly, updating the available results of aortic valve surgery is imperative,
      especially considering the rapid evolution of the transcatheter valve
      implantation procedure. METHODS AND RESULTS: Between 1997 and 2010, 308 patients
      aged 70 years or older underwent aortic valve replacement (AVR) for aortic
      stenosis (AS). Short- and long-term results were analyzed and risk factors for
      long-term mortality were determined. Mean age was 78.5 years and 124 patients
      were aged 80 or older. Concomitant coronary artery bypass grafting (CABG) was
      performed in 46% of the cases. Mean left ventricular ejection fraction (LVEF) was
      52%. Overall observed and expected operative mortality using the Society of
      Thoracic Surgeons-Predicted Risk of Mortality score was 3.9% and 4.8%,
      respectively. Overall survival rates at 1, 5, and 10 years were 88.6%, 71.6%, and
      31.8%, respectively. Predictors of long-term mortality included diabetes;
      preoperative shock; LVEF <= 40%; New York Heart Association functional class III
      or IV; and age. CONCLUSIONS: Short- and long-term results of conventional AVR in
      the elderly prove it to be durable and, especially in relatively low-risk
      patients and patients who require concomitant CABG, operative mortality is
      reasonably low. Conventional AVR +/- CABG remains the gold standard for elderly
      patients with AS.

PMID- 21857142
TI  - Low-dose rosuvastatin improves arterial stiffness in high-risk Japanese patients
      with dyslipdemia in a primary prevention group.
AB  - BACKGROUND: The treatment effects of rosuvastatin on arterial stiffness were
      assessed and compared to those of fluvastatin in high-risk Japanese patients with
      dyslipidemia in a primary prevention group. METHODS AND RESULTS: Patients were
      randomly assigned to either 2.5-5 mg/day of rosuvastatin (Group A) or 20-40
      mg/day of fluvastatin (Group B) and followed up for 12 months. In Group A (n=38),
      there was a progressive reduction in brachial-ankle pulse wave velocity (baPWV)
      along with a decrease in the low-density lipoprotein cholesterol/high-density
      lipoprotein cholesterol (L/H) ratio and high-sensitivity C-reactive protein
      (hsCRP), and the change in baPWV correlated significantly with that of the L/H
      ratio and that of hsCRP after rosuvastatin treatment. In Group B (n=37), although
      fluvastatin achieved a significant improvement in baPWV, L/H ratio, and hsCRP,
      baPWV was significantly greater than that in Group A and showed a significant
      correlation with that of hsCRP alone after fluvastatin treatment. In a subgroup
      of patients (n=26), switching from fluvastatin to rosuvastatin further improved
      baPWV and the L/H ratio without altering hsCRP after 12 months. CONCLUSIONS: Low
      dose rosuvastatin would be more effective than fluvastatin in improving arterial
      stiffness in high-risk Japanese patients with dyslipidemia. The results suggest
      that improvement in arterial stiffness by rosuvastatin mainly depends on its
      strong lipid-lowering effects, whereas that by fluvastatin is strongly dependent
      on the pleiotropic effects, especially an anti-inflammatory action.

PMID- 21857143
TI  - One-year cardiovascular event rates in Japanese outpatients with myocardial
      infarction, stroke, and atrial fibrillation. -Results From the Japan Thrombosis
      Registry for Atrial Fibrillation, Coronary, or Cerebrovascular Events (J-TRACE).
      .
AB  - BACKGROUND: There remains uncertainty about the risk of cardiovascular events in
      stable outpatients with a history of myocardial infarction (MI), stroke, and
      atrial fibrillation in Japan. METHODS AND RESULTS: In the Japan Thrombosis
      Registry for Atrial Fibrillation, Coronary, or Cerebrovascular Events (J-TRACE),
      a nationwide prospective cohort of stable outpatients with a history of MI
      (n=2,291), stroke (n=3,554), and/or atrial fibrillation (n=2,242), 1-year follow
      up data were available for 7,513 of 8,087 patients (follow-up rate: 92.9%). The
      primary endpoint (death/MI/stroke) was reported in 3.53 events per 100 person
      years (95% confidence interval [CI]: 3.11-3.99) within 1 year. The rates of all
      cause death, death from stroke, and death from MI within 1 year were 1.35 (95%CI:
      1.10-1.65), 0.15 (95%CI: 0.08-0.27), and 0.06 (95%CI: 0.02-0.14) per 100 person
      years, respectively. The rate of non-fatal stroke was 1.85 (95%CI: 1.55-2.19),
      while that of non-fatal MI was 0.33 (95%CI: 0.21-0.49). The rate of non-fatal
      stroke was highest among stroke patients (2.95; 95%CI: 2.39-3.60 per 100 person
      years), while that of non-fatal MI was similar across all disease categories.
      Investigator-decided serious non-fatal bleeding events occurred in 0.21 events
      (95%CI: 0.12-0.34) per 100 person-years. CONCLUSIONS: In this large, nationwide
      Japanese registry, the highest stroke event rate was seen in patients with a
      history of stroke.

PMID- 21857144
TI  - Inhibitory interaction between calcium channel blocker and clopidogrel. -Efficacy
      of cilostazol to overcome it-.
AB  - BACKGROUND: The clinical effect of, and additive measures to overcome the
      possible inhibitory calcium channel blocker (CCB)-clopidogrel interaction in
      Asian patients undergoing percutaneous coronary intervention is unknown. METHODS
      AND RESULTS: A total of 900 Korean patients enrolled for the multicenter,
      prospective, randomized Influence of CILostazol-based triple antiplatelet therapy
      ON ischemic complication after drug-eluting stenT implantation (CILON-T) trial
      were divided into 4 groups depending on CCB prescription and type of anti
      platelet therapy (dual [DAT] vs. triple [TAT; addition of cilostazol to DAT]) in
      a 2 * 2 factorial manner. The primary endpoint was a composite of cardiac death,
      non-fatal myocardial infarction and ischemic stroke at 6 months after PCI. On
      treatment platelet reactivity (OPR) was assessed on VerifyNow P2Y12 assay.
      Concomitant CCB use increased OPR in the DAT group (mean +/- SEM: 251.2 +/- 7.6
      vs. 225.6 +/- 5.1; P=0.008), but not in the TAT group (214.5+/-9.1 vs. 203.4 +/-
      5.6; P=0.294). Primary endpoint increased by use of CCB in patients with DAT
      (4.9% vs. 0.9%, P=0.016), but not in those with TAT (0% vs. 1.8%, P=0.346).
      Addition of cilostazol to DAT reduced OPR and clinical events in patients taking
      CCB (P=0.007 for P2Y12 reaction units; P=0.027 for thrombotic events). CCB
      without concomitant cilostazol use was a significant predictor of total
      thrombotic events. CONCLUSIONS: Concomitant use of CCB may weaken the anti
      platelet effect of clopidogrel and increase subsequent thrombotic events in Asian
      subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition
      of cilostazol.

PMID- 21857145
TI  - SEL1L is required for endoplasmic reticulum-associated degradation of misfolded
      luminal proteins but not transmembrane proteins in chicken DT40 cell line.
AB  - Proteins misfolded in the endoplasmic reticulum (ER) are degraded in the cytosol
      by a ubiquitin-dependent proteasome system, a process collectively termed ER
      associated degradation (ERAD). Unraveling the molecular mechanisms of mammalian
      ERAD progresses more slowly than that of yeast ERAD due to the laborious
      procedures required for gene targeting and the redundancy of components. Here, we
      utilized the chicken B lymphocyte-derived DT40 cell line, which exhibits an
      extremely high homologous recombination frequency, to analyze ERAD mechanisms in
      higher eukaryotes. We disrupted the SEL1L gene, which encodes the sole homologue
      of yeast Hrd3p in both chickens and mammals; Hrd3p is a binding partner of yeast
      Hrd1p, an E3 ubiquitin ligase. SEL1L-knockout cells grew only slightly more
      slowly than the wild-type cells. Pulse chase experiments revealed that chicken
      SEL1L was required for ERAD of misfolded luminal proteins such as glycosylated
      NHK and unglycosylated NHK-QQQ but dispensable for that of misfolded
      transmembrane proteins such as NHK(BACE) and CD3-delta, as in mammals. The defect
      of SEL1L-knockout cells in NHK degradation was restored by introduction of not
      only chicken SEL1L but also mouse and human SEL1L. Deletion analysis showed the
      importance of Sel1-like tetratricopeptide repeats but not the fibronectin II
      domain in the function of SEL1L. Thus, our reverse genetic approach using the
      chicken DT40 cell line will provide highly useful information regarding ERAD
      mechanisms in higher eukaryotes which express ERAD components redundantly.

PMID- 21857146
TI  - Gonadotropins up-regulate the expression of enolase 2, but not enolase 1, in the
      rat ovary.
AB  - It has been demonstrated that the glycolytic enzymes, enolase 1 (ENO1) and
      enolase 2 (ENO2), are expressed in the rat ovary.  In the present study, we found
      that mRNA levels of ovarian ENO2 but not ENO1 in normal cycling adult female rats
      changed significantly during the estrous cycle: ovarian ENO2 mRNA levels at
      metestrus were lower than those at estrus.  Single injection of human CG (hCG) or
      equine CG (eCG) into immature (3 week old) rats up-regulated ovarian expression
      of ENO2.  hCG mainly increased ENO2 expression in oocytes and theca cells of
      preantral and antral follicles, and eCG did in theca cells of these follicles. 
      In contrast, hCG and eCG did not affect the expression of ENO1, which was mainly
      expressed in granulosa cells.  These results suggest that endogenous
      gonadotropins up-regulate expression of ENO2 in oocytes and theca cells of
      preantral and antral follicles, which would activate glycolysis in these cells. 
      It is also suggested that the activated glycolysis is necessary for ovarian
      functions such as follicle growth and maturation, and hormone production.

PMID- 21857147
TI  - Dose volume analysis of radiotherapy for inoperable patients with stage I-II
      endometrial carcinoma.
AB  - This study aims to assess the efficacy and toxicity of definitive radiotherapy
      for early-stage endometrial carcinoma. The correlation between CT-based
      dosimetric parameters and clinical outcomes is also evaluated. Between 2002 and
      2006, 10 medically inoperable patients with T1-2 endometrial carcinoma were
      treated with radiotherapy alone. A combination of external beam radiotherapy
      (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) was used for 9
      patients, and one was treated with HDR-ICBT alone. Dose prescription of HDR-ICBT
      was determined in reference to CT images at brachytherapy, and a total dose of 22
      24 Gy in 4 fractions was delivered to the outer perimeter of the uterine corpus.
      Dose-volume parameters of the gross tumor volume (GTV), clinical target volume
      (CTV), and organs at risk were assessed retrospectively using the dose-volume
      histograms derived from the CT image-based treatment planning system. After a
      median follow-up of 55 months, 9 patients were alive without evidence of
      recurrence. One patient died from liver cirrhosis 17 months after radiotherapy.
      Severe acute and late toxicities were not observed in any of the patients.
      Average minimum dose to 90% of GTV and CTV (D90) was 88.0 and 45.9 Gy(EQD2),
      respectively. The minimum dose delivered to 2 cc of the most irradiated volumes
      of the rectum and sigmoid colon (D(2cc)) was 78.9 and 65.9 Gy(EQD2),
      respectively. These patients developed Grade 1 late complications. In this study,
      stage I-II endometrial carcinoma was well-controlled locally with minimum late
      toxicity by radiotherapy alone with HDR-ICBT. 3D image-based brachytherapy may
      potentially deliver a sufficiently high dose to the whole tumor without
      significant increase in dose to surrounding normal tissues.

PMID- 21857148
TI  - T2*-weighted image/T2-weighted image fusion in postimplant dosimetry of prostate
      brachytherapy.
AB  - Computed tomography (CT)/magnetic resonance imaging (MRI) fusion is considered to
      be the best method for postimplant dosimetry of permanent prostate brachytherapy;
      however, it is inconvenient and costly. In T2*-weighted image (T2*-WI), seeds can
      be easily detected without the use of an intravenous contrast material. We
      present a novel method for postimplant dosimetry using T2*-WI/T2-weighted image
      (T2-WI) fusion. We compared the outcomes of T2*-WI/T2-WI fusion-based and CT/T2
      WI fusion-based postimplant dosimetry. Between April 2008 and July 2009, 50
      consecutive prostate cancer patients underwent brachytherapy. All the patients
      were treated with 144 Gy of brachytherapy alone. Dose-volume histogram (DVH)
      parameters (prostate D90, prostate V100, prostate V150, urethral D10, and rectal
      D2cc) were prospectively compared between T2*-WI/T2-WI fusion-based and CT/T2-WI
      fusion-based dosimetry. All the DVH parameters estimated by T2*-WI/T2-WI fusion
      based dosimetry strongly correlated to those estimated by CT/T2-WI fusion-based
      dosimetry (0.77 <= R <= 0.91). No significant difference was observed in these
      parameters between the two methods, except for prostate V150 (p = 0.04). These
      results show that T2*-WI/T2-WI fusion-based dosimetry is comparable or superior
      to MRI-based dosimetry as previously reported, because no intravenous contrast
      material is required. For some patients, rather large differences were observed
      in the value between the 2 methods. We thought these large differences were a
      result of seed miscounts in T2*-WI and shifts in fusion. Improving the image
      quality of T2*-WI and the image acquisition speed of T2*-WI and T2-WI may
      decrease seed miscounts and fusion shifts. Therefore, in the future, T2*-WI/T2-WI
      fusion may be more useful for postimplant dosimetry of prostate brachytherapy.

PMID- 21857149
TI  - Phosphorylation of Ataxin-10 by polo-like kinase 1 is required for cytokinesis.
AB  - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic
      disorder, whose symptoms include cerebellar ataxia and epilepsy. The disease is
      caused by ATTCT expansion in the ATXN10 gene, which encodes the Ataxin-10
      protein. Here we identified polo-like kinase 1 (Plk1) as one of Ataxin-10's
      binding partners. We show that epitope-tagged Ataxin-10 and Plk1
      coimmunoprecipitate, and Plk1 phosphorylates Ataxin-10 at S77 and T82 in vitro.
      Knockdown of ATXN10 with siRNA in HeLa cells results in cytokinesis defects
      multinucleation, which are rescued by wild-type Ataxin-10, but not the phosphor
      deficient 2A mutant. Phosphorylation-specific antibodies towards pS77 detect
      specific signals at the midbody. Like the knockdown, overexpression of the 2A
      mutant generates multinucleated cells and the 2A mutant shows decreased
      interaction with the Plk1 polo-box domain. In addition, we found that Ataxin-10
      is ubiquitinated, and is subject to proteasome-dependent degradation, which is
      delayed in the 2A mutant. We propose a model in which Plk1 phosphorylation of
      Ataxin-10 influences its degradation and cytokinesis, which may provide
      mechanistic insight to SCA10's pathogenesis.

PMID- 21857150
TI  - Mutations to metabolic enzymes in cancer herald a need to unify genetics and
      biochemistry.

PMID- 21857151
TI  - A novel signaling pathway in TNFalpha-induced neutrophil apoptosis.

PMID- 21857152
TI  - Misregulation of mitotic chromosome segregation in a new type of autosomal
      recessive primary microcephaly.
AB  - Primary autosomal recessive microcephaly (MCPH) is a congenital disorder
      characterized by a pronounced reduction of brain size and mental retardation. We
      present here a consanguineous Turkish family clinically diagnosed with MCPH and
      without linkage to any of the known loci (MCPH1-MCPH7). Autozygosity mapping
      identified a homozygous region of 15.8 Mb on chromosome 10q11.23-21.3, most
      likely representing a new locus for MCPH. Although we were unable to identify the
      underlying genetic defect after extensive molecular screening, we could delineate
      a possible molecular function in chromosome segregation by the characterization
      of mitosis in the patients' cells. Analyses of chromosome nondisjunction in T
      lymphocytes and fibroblasts revealed a significantly elevated rate of
      nondisjunction in the patients' cells as compared to controls. Mitotic
      progression was further explored by immunofluorescence analyses of several
      chromosome and spindle associated proteins. We detected a remarkable alteration
      in the anaphase distribution of Aurora B and INCENP, which are key regulators of
      chromosome segregation. In particular, a fraction of both proteins remained
      abnormally loaded on chromosomes during anaphase in MCPH patients' cells while in
      cells of normal control subjects both proteins are completely transferred to the
      spindle midzone. We did not observe any other alterations regarding cell cycle
      progression, chromosome structure, or response to DNA damage. Our observations
      point towards a molecular role of the underlying gene product in the regulation
      of anaphase/telophase progression possibly through interaction with chromosomal
      passenger proteins. In addition, our findings represent further evidence for the
      proposed role of MCPH genes in the regulation of mitotic progression.

PMID- 21857153
TI  - Cooperative control of tumor suppressor genes by a network of oncogenic
      microRNAs.
AB  - Individual microRNAs (miRNAs) have been implicated as oncogenes in experimental
      cancer models and their expression may affect clinical outcomes. To gain a more
      comprehensive view of miRNA action in leukemia, we analyzed miRNA expression
      patters in T-cell leukemia ALL (T-ALL) and cross-referenced the results with an
      unbiased genetic screen and computational analyses.1 We found that multiple
      microRNAs contribute to leukmogenesis and act as multi-targeted regulators of
      several tumor suppressor genes. The oncomirs form a network of overlapping and
      partially redundant interactions that stabilize the malignant phenotype though
      coordinate repression of cellular failsafe programs. The emerging network pattern
      of oncomir action is distinct from the notion of single oncogenic 'driver'
      mutation. We will discuss experimental, diagnostic and therapeutic implications
      of this concept of miRNA action in cancer.

PMID- 21857154
TI  - MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia
      formation.
AB  - Multiciliated cells lining the surface of some vertebrate epithelia are essential
      for various physiological processes, such as airway cleansing. Their apical
      surface is constituted by hundreds of motile cilia, which beat in a coordinated
      manner to generate directional fluid flow. We recently reported the
      identification of microRNAs of the miR-449 family as evolutionary conserved key
      regulators of vertebrate multiciliogenesis. This novel function of miR-449 was
      established using in vivo and in vitro antisense approaches in two distinct
      experimental models. miR-449 strongly accumulated in multiciliated cells in human
      airway epithelium and Xenopus laevis embryonic epidermis, where it triggered
      centriole multiplication and multiciliogenesis by directly repressing the
      Delta/Notch pathway. Our data complement previous reports that showed the
      blocking action of miR-449 on the cell cycle, and unraveled a novel conserved
      mechanism whereby Notch signaling must undergo microRNA-mediated inhibition to
      permit differentiation of ciliated cell progenitors. We review here several
      important questions regarding the links between microRNAs and the Notch pathway
      in the control of cell fate.

PMID- 21857156
TI  - Neuroendocrine regulation of autophagy by leptin.
AB  - The satiety hormone leptin plays a cardinal role in the pathophysiology of
      obesity and diabetes. Here, we show that pharmacological autophagy inducers like
      rapamycin, spermidine and resveratrol can reduce leptin concentrations in the
      serum of mice and that genetic inactivation of the leptin/leptin receptor system
      leads to an increase in autophagy in peripheral tissues including skeletal
      muscle, heart and liver. Paradoxically, intravenous or intraperitoneal
      administration of recombinant leptin protein also induced autophagy in these
      tissues. Moreover, leptin stimulated canonical autophagy in cultured human or
      mouse cell lines, a phenomenon that was coupled to the activation of adenosine
      monophosphate-dependent kianse (AMPK), as well as the inhibition of mammalian
      target of rapamycin (mTOR), and that was confirmed by autophagic flux
      measurements. These results suggest that leptin plays an important role in the
      neuroendocrine control of autophagy, underscoring the existence of novel links
      between metabolic control and autophagic flux that warrant further in-depth
      investigation.

PMID- 21857155
TI  - RNA processing in human mitochondria.
AB  - Mammalian mitochondrial DNA is transcribed as precursor polycistronic transcripts
      containing 13 mRNAs, 2 rRNAs, punctuated by 22 tRNAs. The mechanisms involved in
      the excision of mitochondrial tRNAs from these polycistronic transcripts have
      remained largely unknown. We have investigated the roles of ELAC2, mitochondrial
      RNase P proteins 1 and 3, and pentatricopeptide repeat domain protein 1 in the
      processing of mitochondrial polycistronic transcripts. We used a deep sequencing
      approach to characterize the 5' and 3' ends of processed mitochondrial
      transcripts and provide a detailed map of mitochondrial tRNA processing sites
      affected by these proteins. We show that MRPP1 and MRPP3 process the 5' ends of
      tRNAs and the 5' unconventional, non tRNA containing site of the CO1 transcript.
      By contrast, we find that ELAC2 and PTCD1 affect the 3' end processing of tRNAs.
      Finally, we found that MRPP1 is essential for transcript processing, RNA
      modification, translation and mitochondrial respiration.

PMID- 21857157
TI  - Characterization of human melanoma cell lines and melanocytes by proteome
      analysis.
AB  - We have analyzed the proteomes of two human melanoma cell lines (A375 and 526),
      and of the human melanocytes, (FOM 78), by two-dimensional electrophoresis (2D
      PAGE) and liquid chromatography - tandem mass spectrometry (LC-MS/MS). Our
      comparative proteomic analysis revealed that six proteins were over-expressed in
      both melanoma cell lines as compared to melanocytes: galectin-1, inosine-5'
      monophosphate dehydrogenase 2, serine/threonine-protein phosphatase 2A 65 kDa
      regulatory subunit A alpha isoform, protein DJ-1, cyclophilin A and cofilin-1. We
      show, for the first time, that only specific isoforms of these molecules are over
      expressed in melanoma. Different protein profiles were also found between each
      individual melanoma cell line and the melanocytes. s-Methyl-5-thioadenosine
      phosphorylase, ubiquitin and ribosomal protein S27 a precursor, the basic form of
      protein DJ-1, annexin a1, proliferation associated protein 2g4, isoform alfa
      enolase of alfa-enolase, protein disulfide-isomerase precursor, and elongation
      factor 2 were more strongly expressed in A375 cells compared to melanocytes. In
      526 cells, 60s acidic ribosomal protein p1 and calreticulin precursor were more
      highly expressed than in melanocytes. These molecular differences may help in
      better understanding melanoma development and its different responsiveness to
      therapies. The identified proteins could be exploited as biomarkers or
      therapeutic targets for melanoma.

PMID- 21857158
TI  - Hematopoietic cells as sources for patient-specific iPSCs and disease modeling.
AB  - In addition to being an attractive source for cell replacement therapy, human
      induced pluripotent stem cells (iPSCs) also have great potential for disease
      modeling and drug development. During the recent several years, cell
      reprogramming technologies have evolved to generate virus-free and integration
      free human iPSCs from easily accessible sources such as patient skin fibroblasts
      and peripheral blood samples. Hematopoietic cells from umbilical cord blood banks
      and Epstein Barr virus (EBV) immortalized B lymphocyte repositories represent
      alternative sources for human genetic materials of diverse backgrounds. Ability
      to reprogram these banked blood cells to pluripotency and differentiate them into
      a variety of specialized and functional cell types provides valuable tools for
      studying underlying mechanisms of a broad range of diseases including rare
      inherited disorders. Here we describe the recent advances in generating disease
      specific human iPSCs from these different types of hematopoietic cells and their
      potential applications in disease modeling and regenerative medicine.

PMID- 21857159
TI  - MicroRNA-449 in cell fate determination.
AB  - The microRNAs 449a, b, and c (miR-449) are potent inducers of cell death, cell
      cycle arrest, and/or cell differentiation. They belong to the same family as the
      p53-responsive microRNAs miR-34. Instead of p53, however, the cell cycle
      regulatory transcription factor E2F1 induces miR-449. All members of this
      microRNA family are capable of mediating cell cycle arrest and apoptosis and
      might thereby contribute to tumor suppression. Underlying mechanisms include the
      downregulation of histone acetyl transferases and consecutive activation of p53,
      but also the targeting of cyclin dependent kinases and their association
      partners. Thus, miR-34 and miR-449 provide an asymmetric feedback loop to balance
      E2F and p53 activities. More recently, it was discovered that miR-449 displays
      strong tissue specificity, with high levels in lung and testes. Two model systems
      (Xenopus embryos and cultured human cells) revealed that miR-449 is essential for
      the development of ciliated epithelia, and this appears to depend on miR-449
      mediated modulation of the Notch signaling pathway. Here we summarize our current
      knowledge on cell fate determination by miR-449, and we propose future directions
      to explore the function of miR-449 in cell regulation and organismal development.
      MiR-449 helps to ensure proper cell function but also to avoid cancer, marking a
      close link between cell differentiation and tumor suppression.

PMID- 21857160
TI  - Exploiting tumor metabolism for non-invasive imaging of the therapeutic activity
      of molecularly targeted anticancer agents.
AB  - Rational drug discovery and development requires biomarkers to inform on target
      modulation and treatment efficacy. Many aspects of metabolism are altered in
      cancer, compared to normal tissues, and are often regulated by oncogene
      activation. Non-invasive imaging of spatio-temporal effects of molecularly
      targeted anticancer agents on tumor metabolism has considerable potential in the
      development and use of personalized molecular medicine approaches to cancer
      treatment. Here we describe how non-invasive monitoring of metabolism, using
      primarily magnetic resonance spectroscopy (MRS), can be used to follow treatment
      with novel molecularly targeted anticancer agents. We discuss how the regulation
      of metabolic pathways by oncogenic signaling can affect MRS-detectable metabolic
      signals together with the physiological factors that can influence the measured
      changes. Finally, the translation of these metabolic measurements from pre
      clinical models to patients will be discussed.

PMID- 21857161
TI  - Distinct requirements of hematopoietic stem cell activity and Nras G12D signaling
      in different cell types during leukemogenesis.
AB  - We previously showed that widespread expression of Nras G12D/G12D from its
      endogenous locus in mice leads to an acute myeloproliferative disease (MPD) with
      a complete penetrance, whereas bone marrow-specific expression of Nras G12D/G12D
      in recipient mice did not result in sustained MPD phenotypes but 100% penetrant
      acute T-cell lymphoblastic leukemia/lymphoma (TALL). Such a phenotypic switch
      also is seen in the case of endogenous oncogenic Kras. Two possibilities might
      account for this observation and they are not necessarily mutually exclusive.
      First, the MPD phenotypes in primary Nras G12D/G12D mice might be a transient
      phenomenon attributable to microenvironmental factors that do not necessarily
      imply the potential for long-term maintenance in a hematopoietic-cell autonomous
      manner. Second, it is likely that MPD phenotypes are maintained by genetically
      altered hematopoietic stem cells (HSCs). Nras G12D/G12D signaling might
      substantially alter HSC behaviors (e.g. induce their proliferative exhaustion) so
      that these HSCs no longer sustain MPD phenotypes to a lethal stage in recipient
      mice. Here, we show some preliminary results to support the second hypothesis.
      Our results suggest that different lineages of hematopoietic cells might have
      differential requirements of HSC activity and Nras G12D signaling during
      leukemogenesis.

PMID- 21857162
TI  - Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits
      RAP80.
AB  - DNA double-strand breaks (DSBs) are the most severe type of DNA damage.
      Occurrence of DSBs in the cell activates the DNA damage response (DDR), which
      involves signaling cascades that sense and respond to the damage. Promptly after
      DSB induction, DDR proteins accumulate surrounding both DNA ends and form
      microscopically-visible foci. Recently, we demonstrated that the key DDR protein
      MDC1 directly binds RAP80, an additional DDR protein that recruits BRCA1 to DSBs.
      We provided evidences that the MDC1-RAP80 interaction depends on a ubiquitylation
      event on K-1977 of MDC1. However, it remained unknown whether K-1977 of MDC1 is
      required for the recruitment of RAP80 to DSBs. Here we show that K-1977 of MDC1
      is necessary for focus formation by RAP80. Nevertheless, it has not effect on
      focus formation by gamma-H2AX, MDC1 or 53BP1. The results imply a role for the
      MDC1-RAP80 interaction in focus formation by the RAP80-BRCA1 complex. In light of
      these recent results we discuss several aspects of the complexity of focus
      formation and present a model for the involvement of individual and complex
      recruitment mechanisms in focus formation.

PMID- 21857163
TI  - An efficient method for recombineering GAL4 and QF drivers.
AB  - Neural circuit mapping and manipulation are facilitated by independent control of
      gene expression in pre- and post-synaptic neurons. The GAL4/UAS and Q binary
      transcription systems have the potential to provide this capability. Of
      particular use in neural circuit mapping would be GAL4 and QF drivers specific
      for neurotransmitters and neurotransmitter receptors. Recently available
      Drosophila genomic BAC libraries make recombineering large genes including those
      specific for neurotransmitters and neurotransmitter receptors feasible. Here the
      functionality of cassettes that allow efficient recombineering of GAL4 and QF
      drivers based on kanamycin selection is demonstrated in Drosophila. The cassettes
      should, however, be generalizable for recombineering in other species.

PMID- 21857164
TI  - A fly view of a SUMO-targeted ubiquitin ligase.
AB  - Posttranscriptional modifications of proteins by the ubiquitin and SUMO (Small
      Ubiquitin-related Modifier) pathways regulate the function of protein networks,
      enable cells to respond to signaling cues during development, and to cope with
      the changing environment during adult life. Both modifications can impact protein
      stability, localization, protein-protein interactions and/or function. While both
      pathways have been well studied individually, the long-speculated nature of
      crosstalk between SUMO and ubiquitin pathways has been molecularly enigmatic.
      Recent work in yeast and mammalian cells identified the connection between the
      two pathways in the form of a conserved family of RING finger ubiquitin ligases
      termed SUMO-Targeted ubiquitin ligases (STUbLs). These proteins bind to
      SUMOylated substrates via their SUMO interaction motif and subsequently target
      them for ubiquitylation. Characterization of Degringolade (Dgrn), a STUbL gene in
      the fly genome, enabled us to evaluate the contribution of STUbLs to the
      development of multi-cellular organisms. Analysis of dgrn mutants showed that
      they are required for cyto-nuclear organization during early embryonic
      development, and are likely required to cope with mitotic stress and DNA damage.
      Furthermore, in transcription, STUbLs regulate protein-protein interactions, and
      are part of molecular machinery that regulates co-repressor choice and gene
      expression selectivity during development.

PMID- 21857165
TI  - 2nd Charles Richet et Jules Hericourt workshop: therapeutic antibodies and
      anaphylaxis; May 31-June 1, 2011, Tours, France.
AB  - The Charles Richet and Jules Hericourt workshops honor the memory of Jules
      Hericourt (1850-1938) and Charles Richet (1850-1935) who described the principle
      of serotherapy in 1888 and made the very first attempts to fight cancer with
      serotherapy in 1895. In 1902, Charles Richet and Paul Portier described
      "anaphylaxis," a discovery awarded the Nobel Prize in 1913. The first workshop,
      "Towards the clinical use of mAbs with higher cytolytic efficacy in cancer" was
      held in Tours, France on November 20-21, 2008. The second Charles Richet and
      Jules Hericourt workshop, held May 31-June 1, 2011 at the University of Tours,
      France, was also organized by the Canceropole Grand Ouest. The topic of the
      workshop was therapeutic antibodies and anaphylaxis, a subject rarely addressed
      in congresses focused on monoclonal antibodies. To have discussions about mAb
      side effects with complete objectivity, the congress was organized independently
      of any sponsorship from pharmaceutical companies. This academic event was
      motivated by the high incidence of shocks to cetuximab and the need to compile
      and evaluate scattered information. This growing public health concern was thus
      analyzed from different scientific and medical angles. The first session was
      devoted to acute infusion reactions, with an emphasis on deconvolution of the
      terms "cytokine-release syndrome," "cytokine storms," "anaphylaxis" and their
      epidemiology. This session concluded with the Charles Richet lecture on cetuximab
      anaphylaxis and anti-alphaGal IgE by Thomas Platts-Mills, its discoverer. In the
      next session, the involvement of anti-glycan antibodies in both anaphylaxis and
      delayed hypersensitivity reactions to therapeutic antibodies was discussed. A
      gala dinner was held in the gardens of the beautiful chateau of Villandry, which
      was acquired and restored by Joachim Carvalho, a pupil of Charles Richet's and
      great-grandfather of the present owner. The final session focused on strategies
      to prevent cetuximab anaphylaxis in clinical practice included a variety of
      topics, e.g., premedication, biobetters and biosimilars, skin testing and
      predictive assays. All speakers and attendees enjoyed this very stimulating and
      rewarding meeting, which gathered many people with divergent scientific
      backgrounds and medical specialties.

PMID- 21857167
TI  - Robotic surgery in gynecology. Foreword.

PMID- 21857168
TI  - Comparison of robotic-assisted laparoscopy versus conventional laparoscopy on
      skill acquisition and performance.
AB  - With an increasing adoption of robotics in gynecologic surgery, training and
      acquisition of robotic skills become pertinent. The learning curve for the
      acquisition of robotic skills has been studied using different assessment
      measurements in both the laboratory and surgical setting. In the laboratory
      setting, task acquisition and performance is superior with the robotic platform
      compared with conventional laparoscopy. The 3-dimensional viewing condition
      provides a perceptive advantage. Learning curve for robotics in the clinical
      setting is indirectly assessed. Conclusive statements regarding the learning
      curve comparing robotics with conventional laparoscopy in the surgical setting
      are difficult to make. To date, clinical studies are limited by lack of standard
      definitions and objective assessment measurements.

PMID- 21857169
TI  - Navigating credentialing, privileging, and learning curves in robotics with an
      evidence and experienced-based approach.
AB  - The rapid growth of robot-assisted surgery has created new challenges for
      hospitals to establish credentialing guidelines for new surgeons. Developing and
      maintaining these skills requires frequent practice. Borrowing from the aviation
      model that requires maintaining currency and demonstrating proficiency, robotic
      credentialing guidelines are being developed that will enable hospitals to insure
      patient safety and optimal outcomes. The utilization of computerized robotic
      simulators will, like flight simulators, also help surgeons to maintain and
      improve skills.

PMID- 21857170
TI  - Robotic-assisted surgery for the community gynecologist: can it be adopted?
AB  - The American College of Obstetricians and Gynecologists and the American
      Association of Gynecologic Laparoscopists confirm advantages of conventional
      minimally invasive surgery over laparotomy for benign gynecological procedures;
      however, adoption remains low for the general gynecologist. A systematic search
      for gynecology publications was performed using Medline and Scopus. Available
      data on adoption rates and perioperative outcomes for hysterectomy, myomectomy,
      sacrocolpopexy, and endometriosis were reviewed. Robotic assistance may provide
      an improved rate of minimally invasive surgery adoption with equivalent
      perioperative outcomes to that of conventional techniques. Accessibility and cost
      remain controversial. Formal training programs are being created to address these
      issues.

PMID- 21857171
TI  - Robot-assisted techniques and outcomes in the realm of pelvic reconstructive
      surgery.
AB  - Robotic-assisted surgery for the treatment of pelvic organ prolapse continues to
      grow in popularity as more surgeons adopt this technology. Encompassing all of
      the benefits of laparoscopic surgery, robotic-assisted techniques allow more
      surgeons the ability to perform complex tasks such as meticulous deep pelvic
      dissection and extensive suturing without having to resort to laparotomy. This
      chapter reviews the techniques involved in the robotic approach to pelvic
      reconstructive surgery and discusses the currently available information focusing
      on the outcomes of this procedure.

PMID- 21857172
TI  - Robotic surgery in the obese gynecologic patient.
AB  - Despite robust interest in minimally invasive surgery for obese gynecologic
      patients, widespread use by gynecologic surgeons has been hindered by the
      technical difficulty of completing these procedures. The use of robotic
      assistance to overcome these challenges continues to increase. This study
      discusses the problem of obesity in the United States, provides basic definitions
      and calculations related to the disease, reviews some of the literature
      supporting laparoscopic surgery in obese patients, explores the emergence of
      robotics in this patient population, and offers "surgical pearls" to aid in the
      successful completion of minimally invasive robotic gynecologic procedures in
      heavier patients.

PMID- 21857173
TI  - Fertility preservation and the role of robotics.
AB  - Reproductive surgery employs microsurgical techniques to achieve preservation of
      natural fertility and enhancement of assisted reproductive technologies. The
      minimalist approach of this branch of gynecology has made it the natural
      trailblazer of laparoscopic surgery. Minimally invasive conservative treatment of
      uterine, tubal, ovarian, and peritoneal pathology has long been the gold standard
      for women of reproductive age. Advanced laparoscopic surgery provides clear
      advantages over classic microsurgery, at the cost of significant technical
      challenges. Robot-assisted laparoscopic surgery is now posed to bridge this
      technical gap and promises to be the next revolution in the field of reproductive
      surgery.

PMID- 21857174
TI  - Understanding the financial impact of robotics in gynecologic surgery.
AB  - As surgical innovation and technological advancements evolve, the associated
      costs cannot be overlooked. Currently, the United States health care system is
      undergoing an attempted overhaul with technology such as robotics sitting front
      and center of the financial debate. As patient demand for less invasive surgical
      options increases and standards of practice change, patient outcomes must be
      carefully evaluated to justify the costs increase from traditional, often more
      invasive treatments. The collection of financial data is quite varied among
      hospital systems and so is the models used to determine the costs of robotics.
      Although limited thus far, various cost data have been ascertained in the areas
      of reproductive surgery, hysterectomy (both benign and oncologic), and pelvic
      reconstructive surgery.

PMID- 21857175
TI  - Thyroid disease in pregnancy. Foreword.

PMID- 21857176
TI  - Dietary iodine in pregnancy and postpartum.
AB  - Dietary iodine intake is required for thyroid hormone production. The impact of
      pregnancy on iodine metabolism and homeostasis and the impact of maternal dietary
      iodine status and supplementation on maternal thyroid volume and function are
      reviewed. The effects of iodine status on fetal and neonatal neurodevelopment
      during pregnancy and lactation are discussed.

PMID- 21857177
TI  - Screening for thyroid disease during pregnancy.
AB  - Overt thyroid disease is a well-established risk factor for adverse pregnancy and
      perinatal outcomes. Whether or not subclinical thyroid dysfunction carries these
      same risks has been a matter of controversy. There is inconsistent evidence on
      the association of subclinical thyroid dysfunction (ie, subclinical
      hypothyroidism or isolated hypothyroxinemia) with a woman's pregnancy outcome or
      the cognitive development of her offspring and there are no interventional trials
      that have shown that women with subclinical hypothyroidism who are treated have
      improved outcomes. Until such data are available, it is premature to recommend
      universal screening for thyroid disease in pregnancy or treatment of women who
      have subclinical thyroid dysfunction.

PMID- 21857178
TI  - Overt hyperthyroidism and hypothyroidism during pregnancy.
AB  - The present manuscript provides a definition for, and evaluates the prevalence
      and maternal/fetal/child impact of, overt hyperthyroidism and overt
      hypothyroidism. The prevalence of overt hyperthyroidism is 0.5% and the
      prevalence of overt hyperthyroidism is 0.3%. Overt maternal hyperthyroidism is
      associated with heart failure, preeclampsia, preterm delivery, still birth, and
      neonatal mortality. Overt maternal hypothyroidism is associated with
      preeclampsia, gestational hypertension, cretinism, fetal deaths, and spontaneous
      abortion. A cost-effective analysis for screening and treating overt thyroid
      disease during pregnancy is warranted.

PMID- 21857179
TI  - Basic science and clinical evidence regarding treatment of subclinical
      hypothyroidism during pregnancy.
AB  - The American College of Obstetricians and Gynecologists has stated that routine
      screening and treatment of subclinical hypothyroidism cannot be recommended. Yet,
      after reviewing the same literature, the American Association of Clinical
      Endocrinologists, the American Thyroid Association, and the Endocrine Society
      recommend routine screening and treatment for these women. Our objective is to
      review the basic science and clinical evidence supporting (or refuting) for
      treatment of pregnant women with subclinical disease.

PMID- 21857180
TI  - Subclinical thyroid dysfunction during pregnancy.
AB  - There is compelling data and a rationale for embarking on screening to identify
      pregnant women with some of the multiple classes of subclinical thyroid
      dysfunction. However, the evidence to support such screening and treatment is
      lacking. Several important trials are underway or undergoing peer review that may
      provide answers regarding routine screening and treatment for subclinical thyroid
      dysfunction. Until then, routine screening and treatment for subclinical thyroid
      dysfunction seems premature.

PMID- 21857181
TI  - Thyroid autoantibodies and pregnancy outcomes.
AB  - Autoimmune thyroid disease has been associated with several adverse pregnancy
      outcomes. Increased risk of spontaneous miscarriage and placental abruption in
      women with thyroid antibodies has been confirmed in multiple studies. However,
      benefit of intervention and treatment of autoimmune thyroid disease in otherwise
      euthyroid pregnant women has not been sufficiently studied. The data on the
      association of thyroid antibodies and recurrent pregnancy loss or preterm birth
      are conflicting and a statistically significant association has not been shown in
      large studies. At present time, routine screening and treatment of autoimmune
      thyroid disease in euthyroid pregnant women is not warranted.

PMID- 21857182
TI  - Mood disorders in pregnant women with thyroid dysfunction.
AB  - Both mood disorders and thyroid dysfunction are common in pregnancy and the
      postpartum period and have significant short and long-term implications to the
      mothers and their infants. Thyroid hormones have a multitude of effects on the
      central nervous system, undergo significant changes during pregnancy, and it is
      now widely recognized that disturbances of mood and cognition often emerge in
      association with putative disturbance of thyroid metabolism in the brain. Several
      small studies have shown associations between clinical and subclinical thyroid
      dysfunction and depression during pregnancy or the postpartum period.
      Unfortunately, this relationship between maternal thyroid dysfunction and
      perinatal depression is not well studied.

PMID- 21857185
TI  - Cardiovascular risk reduction in patients with severe mental illness.

PMID- 21857186
TI  - Continuous intracranial pressure monitoring: a last resort in pseudotumor
      cerebri.

PMID- 21857187
TI  - Radiation-induced ocular motor cranial nerve palsies in patients with pituitary
      tumor.
AB  - BACKGROUND: Radiation therapy is often used in the treatment of pituitary tumor.
      Diplopia due to radiation damage to the ocular motor cranial nerves has been
      infrequently reported as a complication in this clinical setting. METHODS:
      Retrospective case series of 6 patients (3 men and 3 women) with pituitary
      adenoma, all of whom developed diplopia following transsphenoidal resection of
      pituitary adenoma with subsequent radiation therapy. None had evidence of tumor
      involvement of the cavernous sinus. RESULTS: Five patients developed sixth nerve
      palsies, 3 unilateral and 2 bilateral, and in 1 patient, a sixth nerve palsy was
      preceded by a fourth cranial nerve palsy. One patient developed third nerve
      palsy. Five of the 6 patients had a growth hormone-secreting pituitary tumor with
      acromegaly. Following transsphenoidal surgery in all 6 patients (2 had 2
      surgeries), 4 had 2 radiation treatments consisting of either radiosurgery (2
      patients) or external beam radiation followed by radiosurgery (2 patients).
      CONCLUSIONS: Patients with pituitary tumors treated multiple times with various
      forms of radiation therapy are at risk to sustain ocular motor cranial nerve
      injury. The prevalence of acromegalic patients in this study reflects an
      aggressive attempt to salvage patients with recalcitrant growth hormone elevation
      and may place the patient at a greater risk for ocular motor cranial nerve
      damage.

PMID- 21857189
TI  - Central retinal artery occlusion and recurrent papillitis in a patient with
      incomplete Behcet disease.
AB  - A 40-year-old man presented with painless sudden visual loss due to a central
      retinal artery occlusion (CRAO) in his right eye. Three months later, he had
      painless acute visual loss in his left eye with visual acuity of 20/100 and a
      swollen optic disc. After oral prednisone treatment, the disc swelling resolved
      and acuity recovered to 20/20. Five months later, the patient experienced another
      episode of vision loss in the left eye associated with optic disc edema. With
      steroid therapy, he regained 20/20 acuity once again. With a history of recurrent
      oral ulcers, fluorescein angiography showing obliterative retinal vasculitis in
      the right eye, and steroid responsive optic neuropathy in the left eye, we made
      the diagnosis of incomplete Behcet disease.

PMID- 21857190
TI  - Optic pathway gliomas.
AB  - BACKGROUND: Childhood optic pathway gliomas (OPGs) are low-grade neoplasms
      intrinsic to the optic nerve, optic chiasm, tracts, and radiations. The
      management of OPGs is still a highly controversial topic among neuro
      ophthalmologists. EVIDENCE ACQUISITION: Authors' personal experience and
      literature review. RESULTS: This review describes our current understanding of
      the behavior of OPGs and discusses advances in their imaging, evaluation, and
      management. Patients with OPGs that progress are typically treated with
      chemotherapy using carboplatin and vincristine; however, newer approaches to
      therapy are being explored. CONCLUSIONS: Although chemotherapy is the mainstay of
      treatment when indicated, multicenter collaborative studies involving oncologists
      and neuro-ophthalmologists, both retrospective and prospective, are still needed
      to establish evidence-based guidelines for the management of children with OPGs.

PMID- 21857193
TI  - Structural-functional dissociation observed during recovery phase of optic
      neuropathies.

PMID- 21857191
TI  - Progressive aphasia and vision loss in a teen-aged girl.

PMID- 21857196
TI  - Quality improvement in perinatal care.

PMID- 21857197
TI  - Does pay for performance improve patient care?

PMID- 21857199
TI  - The development of an obstetric triage acuity tool.
AB  - The purpose of this article is to describe the journey a multicampus hospital
      system took to improve the obstetric triage process. A review of literature
      revealed no current comprehensive obstetric acuity tool, and thus our team
      developed a tool with a patient flow process, revised and updated triage nurse
      competencies, and then educated the nurses about the new tool and process. Data
      were collected to assess the functionality of the new process in assigning acuity
      upon patient arrival, conveying appropriate acuities based on patient complaints,
      and initiating the medical screening examination, all within prescribed time
      intervals. Initially data indicated that processes were still not optimal, and re
      education was provided for all triage nurses. This improved all data points. The
      result of this QI project is that our patients are now seen based on their acuity
      within designated time frames.

PMID- 21857200
TI  - A state-wide obstetric hemorrhage quality improvement initiative.
AB  - PURPOSE: The mission of the California Maternal Quality Care Collaborative is to
      eliminate preventable maternal death and injury and to promote equitable
      maternity care in California. This article describes California Maternal Quality
      Care Collaborative's (CMQCC's) statewide multistakeholder quality improvement
      initiative to improve readiness, recognition, response, and reporting of maternal
      hemorrhage at birth and details the essential role of nurses in its success.
      PROJECT DESIGN AND APPROACH: In partnership with the State Department of
      Maternal, Child, and Adolescent Health, CMQCC identified maternal hemorrhage as a
      significant quality improvement opportunity. CMQCC organized a multidisciplinary,
      multistakeholder task force to develop a strategy for addressing obstetric (OB)
      hemorrhage. PROJECT DESCRIPTION: The OB Hemorrhage Task Force, co-chaired by
      nurse and physician team leaders, identified four priorities for action and
      developed a comprehensive hemorrhage guideline. CMQCC is using a multilevel
      strategy to disseminate the guideline, including an open access toolkit, a
      minimal support-mentoring model, a county partnership model, and a 30-hospital
      learning collaborative. CLINICAL IMPLICATIONS: In participating hospitals, nurses
      have been the primary drivers in developing both general and massive hemorrhage
      policies and procedures, ensuring the availability of critical supplies,
      organizing team debriefing after a stage 2 (or greater) hemorrhage, hosting
      skills stations for measuring blood loss, and running obstetric (OB) hemorrhage
      drills. Each of these activities requires effort and leadership skill, even in
      hospitals where clinicians are convinced that these changes are needed. In some
      hospitals, the burden to convince physicians of the value of these new practices
      has rested primarily upon nurses. Thus, the statewide initiative in which nurse
      and physician leaders work together models the value of teamwork and provides a
      real-time demonstration of the potential for effective interdisciplinary
      collaboration to make a difference in the quality of care that can be achieved.
      Nurses provide significant leadership in multidisciplinary, multistakeholder
      quality projects in California. Ensuring that nurses have the opportunity to
      participate in formal leadership of these teams and are represented at all
      workgroup levels is critical to the overall initiative. Nurses brought key
      understanding of operational issues within and across departments, mobilized
      engagement across the state through the regional perinatal programs, and
      developed innovative approaches to solving clinical problems during
      implementation. Nursing leadership and integrated participation was especially
      critical in considering the needs of lower-resource settings, and was essential
      to the toolkit's enthusiastic adoption at the unit/service level in facilities
      across the state.

PMID- 21857201
TI  - Implementation of a system-wide policy for labor induction.
AB  - Standardization of key clinical protocols and policies in the inpatient obstetric
      setting has the potential to improve care processes, ultimately resulting in
      better patient outcomes and decreased professional liability. Increasingly
      hospitals and healthcare systems are realizing benefits with adoption of
      standardization as a strategy for quality care improvement. We describe
      successful system-wide development and implementation of a policy for labor
      induction including avoidance of elective births before 39 completed weeks of
      gestation and standardization of various aspects of the labor induction process,
      with the goal of providing safer care.

PMID- 21857202
TI  - A system-wide initiative to prevent retained vaginal sponges.
AB  - As any perinatal nurse knows, retained vaginal sponges are an obstetrical and
      postpartum patient safety problem. As surgical sponge counts are not routine in
      some obstetrical units for vaginal births, our healthcare system chose to
      institute a rigorous process to eliminate retained sponges in all vaginal births.
      This article describes this process, along with the lessons learned, when
      Catholic Healthcare West implemented the Sponge ACCOUNTing System in its 32
      hospitals in California, Arizona, and Nevada. Implementation of this process
      involved the standardization of practice for obstetricians, certified nurse
      midwives, nurses, obstetric technicians, radiologists, and radiology technicians
      in the management and accounting of surgical sponges.

PMID- 21857204
TI  - Continuous quality improvement in nutrition.

PMID- 21857205
TI  - HIT potential to transform quality improvement.

PMID- 21857206
TI  - Global quality improvement: where are we?

PMID- 21857208
TI  - Improving pregnancy outcomes.

PMID- 21857209
TI  - Regarding the study by Hutti, Armstrong, and Myers (MCN36(2), 2011).

PMID- 21857210
TI  - Dabigatran etexilate (Pradaxa) for the treatment of atrial fibrillation.

PMID- 21857211
TI  - Legal issues in adolescent care.

PMID- 21857212
TI  - Cholecystitis and HIDA scan.

PMID- 21857215
TI  - Nurse practitioner management of chronic musculoskeletal pain: a chart review.
AB  - This study explored NPs' management of chronic musculoskeletal pain via a record
      review of 50 uninsured patients. The findings include a summary of the
      utilization of services and treatments along with demographic data.
      Recommendations for education, practice, and further research are discussed.

PMID- 21857216
TI  - Contemporary approaches to adult obesity treatment.
AB  - Adult obesity is a common health problem associated with significant adverse
      health outcomes. Evidence-based guidelines support intensive nutrition and
      behavioral counseling and moderate physical exercise. Pharmacotherapy agents are
      available for long-term use to enhance weight loss efforts for some patients.

PMID- 21857217
TI  - Stopping HAIs at their source.
AB  - Healthcare-associated infections caused by multidrug-resistant organisms are a
      serious threat to public health. Changes in healthcare delivery have caused these
      infections to affect the community. NPs should be aware of the most prevalent
      multidrug-resistant organisms and effective methods to prevent the spread of
      infection.

PMID- 21857219
TI  - Vascular burden and cognitive functioning in depressed older adults.
AB  - BACKGROUND: Vascular burden is known to contribute to geriatric depression and
      cognitive impairment. The objective of our study was to evaluate the relationship
      between vascular burden and pattern of cognitive impairment in older adults with
      depression. METHODS: Ninety-four community-dwelling older adults (mean age = 70.8
      years; SD = 7.63) diagnosed with major depression were recruited to participate
      in the tai chi complementary use study aimed to improve antidepressant response
      to an antidepressant medication. All participants received comprehensive
      evaluations of depression, apathy, and vascular risk factors, and completed a
      battery of cognitive measures of memory, cognitive control, verbal fluency, and
      attention. RESULTS: The severity of vascular burden was significantly correlated
      with depression severity and impaired performance on measures of cognitive
      control (i.e., inhibition/mental flexibility), and attention, but not memory or
      verbal fluency. Neither the severity of comorbid apathy nor medical illness
      burden was related to cognitive impairment. CONCLUSIONS: Vascular burden in older
      depressed adults contributes to cognitive impairment, particularly in domains of
      attention and cognitive control. Our findings suggest that aggressive treatment
      of vascular risk factors may reduce risk for further cognitive decline in
      depressed older adults.

PMID- 21857220
TI  - Self-reported cognitive complaints in elderly bipolar patients.
AB  - BACKGROUND: Patients with bipolar disorder are at risk to develop cognitive
      decline in the course of their illness. This may affect their ability to monitor
      and detect their own cognitive functioning (anosognosia). The aim of this study
      was to determine whether subjective cognitive complaints were associated with
      objective neuropsychologic performance and to consider the role of frontal lobe
      dysfunction in the awareness of cognitive impairment. METHOD: A total of 101
      euthymic elderly bipolar patients and 74 healthy comparison subjects were
      assessed using a comprehensive neuropsychologic battery. The Cognitive Failure
      Questionnaire was used to determine subjective cognitive complaints. RESULTS:
      Elderly bipolar patients had no more subjective cognitive complaints than
      comparison subjects, whereas they showed less cognitive functioning in several
      domains. Having few subjective cognitive complaints was associated with poorer
      attentional and executive functioning. CONCLUSIONS: Impaired awareness of
      cognition might be a reflection of cognitive deterioration and could influence
      treatment. Evaluation of cognitive functioning in elderly bipolar patients should
      be part of the treatment program regardless of subjective complaints.

PMID- 21857221
TI  - Vitamin D requirements and supplementation during pregnancy.
AB  - PURPOSE OF REVIEW: The topic of vitamin D supplementation during pregnancy is
      very controversial. This review attempts to provide balanced knowledge with
      respect to this topic gained in the past 18 months. RECENT FINDINGS: Two recent
      reports, one by the Institute of Medicine, and one by The Endocrine Society are
      greatly divergent with respect to the nutritional requirement for vitamin D, as
      well as, the level of circulating 25-hydroxyvitamin D that is desirable. These
      recommendations will be discussed along with recent observational data and a
      recently completed randomized controlled trial dealing with vitamin D
      requirements during pregnancy. SUMMARY: Current evidence supports the concept
      that circulating 25-hydroxyvitamin D should be 40-60  ng/ml (100-150  nmol)
      during pregnancy and a daily intake of 4000  IU vitamin D3 is required to attain
      that circulating level.

PMID- 21857222
TI  - Assessment of liver disease (noninvasive methods).
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight new findings
      published in 2010-2011 related to noninvasive fibrosis assessment in
      HIV/hepatitis C virus (HCV) co-infected patients. Overall, in 2010-2011, 15
      studies were published, of which two were excluded because they were published in
      languages other than English. RECENT FINDINGS: Eleven studies focused on serum
      marker panels. Studies sought to validate established panels in HIV/HCV co
      infected patients often by comparing multiple serum marker panels in the same
      population; establish new marker panels using combinations of markers used in
      previously validated panels; and develop new marker panels using novel
      methodology. Overall, all panels performed within similar ranges of diagnostic
      accuracy as measured by the area under the receiver operating characteristic
      curve (AUROC) but the FibroMeter panel and its derivations achieved the highest
      performance. Four studies focused on transient elastography. Two studies
      confirmed its accuracy for identifying fibrosis and cirrhosis and two studies
      confirmed that misclassification rates are higher in the presence of elevated
      triglycerides and steatosis. SUMMARY: Overall, performance of transient
      elastography appeared superior to the majority of serum marker panels for the
      detection of significant fibrosis and cirrhosis in HIV/HCV co-infected patients.
      Challenges of widespread application of transient elastography remain high
      misclassification in some subgroups, lack of standardized cut-points and lack of
      widespread availability. Panels that were newly developed in 2010-2011
      specifically for HIV/HCV appeared to perform better than existing panels such as
      APRI and FIB-4; however, additional external validation will be needed to confirm
      their accuracy.

PMID- 21857223
TI  - Synthetic vaginal mesh for pelvic organ prolapse.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recently published
      comparative trials on synthetic vaginal mesh versus traditional native tissue
      repairs for pelvic organ prolapse. RECENT FINDINGS: Although studies suggest
      benefit from the use of synthetic vaginal mesh for anterior compartment prolapse,
      data are limited on the use of mesh for posterior and apical prolapse when
      compared with native tissue repair. The benefits of a more durable repair must be
      weighed against risks such as the development of de-novo stress incontinence,
      visceral injury, dyspareunia, pelvic pain and mesh contraction, exposure and
      extrusion requiring reoperation. Furthermore, the success rates of native tissue
      repairs are higher than previously considered using updated validated composite
      outcomes that incorporate both subjective relief of bulge and objective cure
      defined as prolapse above the hymenal ring. SUMMARY: Surgeons placing synthetic
      mesh for pelvic organ prolapse should counsel patients regarding the potential
      benefits, risks, and alternatives including native tissue repairs. Level 1
      evidence suggests anterior synthetic mesh may be superior to anterior repair.
      Expert opinion suggests potential benefit of vaginal mesh for recurrences,
      hysteropexy, and advanced prolapse in patients with medical co-morbidities
      precluding invasive open and endoscopic sacrocolpopexies; however, comparative
      clinical trials with long-term data are needed.

PMID- 21857225
TI  - New insights on chemically induced animal models of systemic sclerosis.
AB  - PURPOSE OF REVIEW: To discuss the most recent published studies on chemical
      induced animal models of systemic sclerosis (SSc) and to precise the important
      signalling pathways that lead to the initiation and progression of the disease in
      these models. RECENT FINDINGS: Environmental factors undoubtedly contribute to
      the initiation and the development of SSc. Among those factors, bleomycin has
      been identified as a possible SSc-inducing substance in mice. The bleomycin model
      mimics the inflammatory changes observed in the early phase of the disease. This
      model has been extensively studied and has allowed identification of several key
      pathways activated in the human disease. More recently, a new chemical-induced
      model of scleroderma has been developed in mice using daily intradermal
      injections of a solution generating hypochlorous acid (HOCl)-model. This HOCl
      model recapitulates the whole spectrum of the human disease, as fibrosis,
      inflammation, autoimmunity and vasculopathy can be observed in mice and brought
      new arguments for a major role of reactive oxygen species in the induction of
      local and systemic fibrosis. SUMMARY: Chemically induced models truly develop a
      SSc-like disease and argue for a crucial role of ROS in SSc.

PMID- 21857224
TI  - New animal models of cystic fibrosis:  what are they teaching us?
AB  - PURPOSE OF REVIEW: Cystic fibrosis is the first human genetic disease to benefit
      from the directed engineering of three different species of animal models (mice,
      pigs, and ferrets). Recent studies on the cystic fibrosis pig and ferret models
      are providing new information about the pathophysiology of cystic fibrosis in
      various organ systems. Additionally, new conditional cystic fibrosis
      transmembrane conductance regulator (CFTR) knockout mice are teaching unexpected
      lessons about CFTR function in surprising cellular locations. Comparisons between
      these animal models and the human condition are key to dissecting the
      complexities of disease pathophysiology in cystic fibrosis. RECENT FINDINGS:
      Cystic fibrosis pigs and ferrets have provided new models to study the
      spontaneous development of disease in the lung and pancreas, two organs that are
      largely spared overt spontaneous disease in cystic fibrosis mice. New cystic
      fibrosis mouse models are now interrogating CFTR functions involved in growth and
      inflammation at an organ-based level using conditional knockout technology.
      Together, these models are providing new insights on the human condition.
      SUMMARY: Basic and clinical cystic fibrosis research will benefit greatly from
      the comparative pathophysiology of cystic fibrosis mice, pigs, and ferrets. Both
      similarities and differences between these three cystic fibrosis models will
      inform pathophysiologically important mechanisms of CFTR function in humans and
      aid in the development of both organ-specific and general therapies for cystic
      fibrosis.

PMID- 21857226
TI  - Hematopoietic stem cell transplantation for systemic sclerosis:  history and
      current status.
AB  - PURPOSE OF REVIEW: Systemic sclerosis (SSc) remains one of the last severe
      autoimmune disease with a poor prognosis and modest response to immunosuppressive
      therapy. Mortality in severe diffuse disease with internal organ involvement is
      elevated. Autologous hematopoietic transplantation (HSCT) has emerged in the last
      decade as a promising disease-modifying treatment. RECENT FINDINGS: In phase I/II
      trials, HSCT has demonstrated to induce impressive reversal of skin fibrosis,
      neoangiogenesis, improved functionality and quality of life, and stabilization of
      internal organ function. Treatment-related mortality was reduced over time by
      better pretransplant evaluation and by treating patients earlier in disease.
      SUMMARY: Two out of three randomized trials of autologous HSCT for SSc have been
      concluded: the nonmyeloablative American Systemic Sclerosis Immune Suppression
      versus Transplant, and Autologous Stem cell Transplantation International
      Scleroderma. The myeloablative Scleroderma Cyclophosphamide versus Transplant
      instead is still recruiting patients. The soon expected results from these trials
      should clarify the role of autologous HSCT in the challenging management of
      severe SSc.

PMID- 21857227
TI  - Female incontinence:  long-term results of slings.
AB  - PURPOSE OF REVIEW: Several different sling procedures are currently in use and
      most of them are newly developed. Despite the fact that they are widely in use,
      knowledge about their long-term efficacy, morbidity, and functional sequeal is
      scarce. The aim of the present review is to provide an update of several
      different procedures. RECENT FINDINGS: The tension-free vaginal tape is the best
      studied and documented procedure with excellent long-term outcome data and low
      rates of complications. Tension-free vaginal tape appears to be followed by
      significantly higher objective cure rates than transobturator tape. Concerning
      comparison of different types of transobturator tape, no significant differences
      were found so far. Minislings still need to be evaluated concerning long-term
      safety and efficacy. SUMMARY: Tension-free vaginal tape and transobturator tape
      are equally effective; for assessment of new approaches, surgical long-term data
      are mandatory.

PMID- 21857228
TI  - The impact of a computerised whiteboard system on digit preference bias in the
      recording of emergency department process times.
AB  - OBJECTIVE: Digit preference bias has previously been described in a number of
      different clinical settings including the emergency department. This study aimed
      to assess whether the implementation of a computerised recording system affects
      the digit preference bias in recording of times of arrival, assessment and
      departure at an emergency department. METHODS: A preintervention/postintervention
      study was undertaken in a type 1 district general hospital emergency department
      that receives approximately 70 000 attendances per annum. Consecutive 8-week
      samples were taken before and after the introduction of an electronic
      whiteboard/patient tracking system. Timings of arrival, nursing and medical
      assessment and departure were compared. RESULTS: Twelve thousand four hundred and
      ninety-three patients presented during the 8-week control period and 11 758
      patients presented in the 8-week period after the introduction of electronic data
      capturing. Within the control group, over 80% of the nursing assessment (82.7%),
      medical examination (92.5%) and departure times (92.7%) ended in '0' or '5',
      compared with just over 20% after electronic recordings (22.0, 21.7 and 21.8%
      respectively). CONCLUSION: The introduction of the patient tracking system
      eliminated the digit preference bias found in recording of the time of nursing
      assessment, examination and departure that was present in the preintervention
      data.

PMID- 21857229
TI  - Mass screening of emergency department visitors for occult radionuclide
      contamination.
AB  - OBJECTIVE: To design an effective, efficient, and affordable radiation
      surveillance system to screen every emergency department (ED) visitor before they
      enter the ED. METHODS: We chose fluoro-2-deoxyglucose as the source of gamma
      rays. We collected all available radiation dosimeters in the hospital, designed
      four modules of measurement, and estimated the distance from visitors to the
      dosimeter. The maximal distances containing 95% (D95%) of visitors were obtained
      for the sensitivity tests of every dosimeter in each module. The surveillance
      system was designed as a dual-monitor system to reduce the possibility of
      machinery failure. We checked system reliability, followed by a 2-year validation
      test. RESULTS: Four dosimeters passed the dose-distance tests. For ambulatory
      visitors, the triage wall-mounted module had the shortest D95%, followed by the
      triage nurse module. For recumbent visitors, the triage nurse module had the
      shortest D95%, followed by the triage wall-mounted module. Area monitors showed
      better sensitivities than personal dosimeters; however, triage nurses could not
      wear them because of their size and weight. We used an area monitor on the triage
      post and the individual dosimeter on the triage nurse as our surveillance system.
      This system worked well in the reliability test. A sentinel event occurred in the
      validation test, with a peak dose of 49 136 nSv/h. CONCLUSION: Radiation threat
      to the ED, although uncommon, is real. For the safety of everyone in the ED, you
      can install an effective, efficient, but affordable surveillance system similar
      to ours if your ED is not exempted from this threat.

PMID- 21857230
TI  - A large health system's approach to utilization of the genetic counselor CPT(r)
      96040 code.
AB  - PURPOSE: : In 2007, CPT(r) code 96040 was approved for genetic counseling
      services provided by nonphysician providers. Because of professional recognition
      and licensure limitations, experiences in direct billing by genetic counselors
      for these services are limited. A minority of genetics clinics report using this
      code because of limitations, including perceived denial of the code and confusion
      regarding compliant use of this code. We present results of our approach to 96040
      billing for genetic counseling services under a supervising physicians National
      Provider ID number in a strategy for integration of genetics services within
      nongenetics specialty departments of a large academic medical center. METHODS: :
      The 96040 billing encounters were tracked for a 14-month period and analyzed for
      reimbursement by private payers. Association of denial by diagnosis code or
      specialty of genetics service was statistically analyzed. Descriptive data
      regarding appointment availability are also summarized. RESULTS: : Of 350
      encounters January 2008 to February 2009, 289 (82%) were billed to private
      payers. Of these, 62.6% received some level of reimbursement. No association was
      seen for denial when analyzed by the diagnosis code or by genetics focus. Through
      this model, genetics appointment availability minimally doubled. CONCLUSION: :
      Using 96040 allowed for expanding access to genetics services, increased
      appointment availability, and was successful in obtaining reimbursement for more
      than half of encounters billed.

PMID- 21857231
TI  - Feasibility of a pancreatic cancer surveillance program from a psychological
      point of view.
AB  - PURPOSE: : The success of any surveillance program depends not solely on its
      technological aspects but also on the commitment of participants to adhere to
      follow-up investigations, which is influenced by the psychological impact of
      surveillance. This study investigates the psychological impact of participating
      in a pancreatic cancer surveillance program. METHODS: : High-risk individuals
      participating in an endoscopic ultrasonography-magnetic resonance imaging-based
      pancreatic cancer surveillance program received a questionnaire assessing
      experiences with endoscopic ultrasonography and magnetic resonance imaging,
      reasons to participate, psychological distress, and benefits and barriers of
      surveillance. High-risk individuals were individuals with a strong family history
      of pancreatic cancer or carriers of pancreatic cancer-prone gene mutations.
      RESULTS: : Sixty-nine participants (85%) completed the questionnaire.
      Surveillance was reported as "very to extremely uncomfortable" by 15% for
      magnetic resonance imaging and 14% for endoscopic ultrasonography. Most reported
      reason to participate was that pancreatic cancer might be detected in a curable
      stage. Abnormalities were detected in 27 respondents, resulting in surgical
      resection in one individual and a shorter follow-up interval in five individuals.
      Surveillance outcomes did not influence cancer worries. Overall, 29% was "often"
      or "almost always" concerned about developing cancer. Six respondents (9%) had
      clinical levels of depression and/or anxiety. According to 88% of respondents,
      advantages of surveillance outweighed disadvantages. CONCLUSIONS: : Although
      endoscopic ultrasonography is more invasive than magnetic resonance imaging,
      endoscopic ultrasonography was not perceived as more burdensome. Despite one
      third of respondents worrying frequently about cancer, this was not related to
      the surveillance outcomes. Anxiety and depression levels were comparable with the
      general population norms. Advantages of participation outweighed disadvantages
      according to the majority of respondents. From a psychological point of view,
      pancreatic cancer surveillance in high-risk individuals is feasible and
      justified.

PMID- 21857232
TI  - Immediate loading of freestanding implants using cortical satellite implants: 3
      year results of an ongoing prospective study.
AB  - BACKGROUND: It has previously been demonstrated that immediate full occlusal
      loading of freestanding anterior implants can be performed using cortical
      satellite implants, obtaining a success rate similar to conventional protocols.
      The aim of this report was to present the outcomes after 36 months after initial
      placement. METHODS: Twenty patients received 2 single-standing titanium screw
      implants, which were stabilized during healing time with cortical satellite
      implants. Immediately after surgery, mandibular overdentures were placed using
      ball attachments. The satellite implants were removed after 3 months. RESULTS:
      Implant survival analysis showed a 100% success rate. The following parameters
      were assessed during the study: Periotest values, -5.89 (minimum: -7.00, maximum:
      -4.00); radiographic assessment of bone resorption, 0.51 mm (minimum: 0.00 mm,
      maximum: 1.50 mm); and pocket probing depth, 2.60 mm (minimum: 1.00 mm, maximum:
      8.00 mm). CONCLUSIONS: The results suggest that immediate loading of freestanding
      implants stabilized with satellite implants is a successful concept at 3 years
      observation time.

PMID- 21857233
TI  - The relationship between maternal opioid agonists and psychiatric medications on
      length of hospitalization for neonatal abstinence syndrome.
AB  - OBJECTIVE: To examine the relationship between maternal opioid agonists,
      methadone, or buprenorphine (BPH), and concurrent psychiatric medication use on
      length of hospitalization (LOS) among infants with neonatal abstinence syndrome
      (NAS). METHODS: We reviewed the charts of infants born at Boston Medical Center
      between 2003 and 2009 with a diagnosis of NAS whose mothers were prescribed
      methadone or BPH for opiate addiction. Univariate and multivariate linear
      regression analyses were used to examine associations between maternal opioid
      substitution concurrent with psychiatric medication use and infant LOS. We also
      tested whether exposure to BPH was associated with a shorter hospitalization.
      RESULTS: A total of 273 mother-infant pairs were identified. The average LOS for
      all infants was 22.9 days (SD: 10.9). In bivariate analyses, maternal use of any
      psychiatric medication was associated with a longer infant LOS (P < 0.005).
      Compared with those prescribed methadone alone (n = 158), those also taking
      benzodiazepines (n = 56) had a 5.88-day longer LOS (95% confidence interval [CI]:
      2.15-9.60, P = 0.002). Infants of mothers taking methadone plus an selective
      serotonin re-uptake inhibitor (n = 51) had a longer LOS (beta = 4.47, 95% CI:
      1.15-7.79) compared to methadone alone; results remained significant in an
      initial multivariate model, however the effect was attenuated when additional
      psychiatric medication use was added to the model. Compared with those exposed to
      methadone, those exposed to BPH (n = 22) had a significantly shorter LOS (beta = 
      7.35, CI: -0.18 to -14.52, P = 0.04). CONCLUSIONS: Maternal use of prescribed
      methadone and benzodiazepines, compared to methadone alone, increased LOS for
      infants with NAS by 6 days. Maternal use of BPH was associated with a shorter
      LOS.

PMID- 21857234
TI  - Isolated creatine kinase-MB rise with normal cardiac troponins: a strange
      occurrence with difficult interpretation.
AB  - A 37-year-old man is admitted to the hospital for retrosternal chest pain lasting
      more than 30  min and nonspecific ECG findings. Serial assays of cardiac
      biomarkers reveal an isolated elevation of creatine kinase-MB and negative
      troponin levels. A coronary angiography shows normal vessels in the presence of a
      Thrombolysis in Myocardial Infarction (TIMI) 2 flow. How should this patient be
      managed and treated? Is it a myocardial infarction? We here provide a review of
      the relevant literature and suggest that such a strange condition, for which
      several explanations are possible, involves a worse prognosis than for normal
      creatine kinase-MB and troponins.

PMID- 21857235
TI  - Current practice and opinions regarding the use of oropharyngeal throat packs in
      the United Kingdom.
AB  - OBJECTIVE: : The aim of this study was to establish the current practice and
      opinions regarding responsibilities when using OPTPs in the United Kingdom.
      METHODS: : A total of 330 anonymous questionnaires exploring the use, attitudes,
      opinions, and experiences of surgeons (n = 180) and anesthetists (n = 150) were
      disseminated. RESULTS: : The response rate was 82%. Just less than one-third of
      surgeons and just more than one-third of anesthetists rarely or never use OPTP.
      Just more than half of the surgeons responding were aware of 1 to 4 nonfatal
      adverse events. Two surgeons and 1 anesthetist were aware of 1 to 4 fatalities
      relating to a retained OPTP. There was a marked difference in opinions regarding
      OPTP removal and whose ultimate responsibility it is to remove. CONCLUSIONS: :
      The use of the OPTP is not routine in the United Kingdom, and adverse incidents
      occasionally occur when used. It would also seem that, despite the recent
      publicity and advice documents during the last few years, theater teams may still
      be at variance with regard to related responsibilities. As such, although
      objective data emerge, we support a unified practice and policy at the Trust and
      national level that all teams should adhere to when appropriate.

PMID- 21857236
TI  - Physician reporting of clinically significant events through a computerized
      patient sign-out system.
AB  - OBJECTIVES: : Although electronic reporting systems for near-misses and adverse
      events have been implemented nationwide, physician participation in such systems
      has typically been very limited. Previous efforts to improve such rates have met
      with some success but may be costly and time-consuming. To improve events
      reporting rates at our academic medical center, we incorporated a physician
      reporting module into the computer software that house officers already use for
      their daily sign-out routine. METHODS: : During the period between January 1 and
      June 30, 2009, house staff were asked to report a set of 13 predefined
      "clinically significant events" such as cardiopulmonary arrests and unexpected
      transfers to the intensive care unit. Entries were maintained in an
      administrative data collection module and were reviewed daily by the residency
      program director and chief residents. RESULTS: : House staff reported
      approximately 12 incidents per month. A survey of the intern class (the heaviest
      users of system) showed that the principal barriers to physician reporting at our
      facility were related to ease of use, time pressure, and fear of disciplinary
      actions. Information gleaned from the reports has been useful in modifying a
      number of patient care processes on the medicine service. CONCLUSIONS: : Our
      experience suggests that if a training program makes it easy for the house
      officer to report events during routine work duties, by integrating the reporting
      system into the tools of daily patient care, physicians will become willing
      participants in the process. A handheld version of such a reporting system holds
      promise for even greater physician participation in the future.

PMID- 21857237
TI  - The partnership with patients: a call to action for leaders.

PMID- 21857238
TI  - Medicines reconciliation using a shared electronic health care record.
AB  - OBJECTIVE: : This study aimed to evaluate the use of a shared electronic primary
      health care record (EHR) to assist with medicines reconciliation in the hospital
      from admission to discharge. METHODS: : This is a prospective cross-sectional,
      comparison evaluation for 2 phases, in a short-term elderly admissions ward in
      the United Kingdom. In phase 1, full reconciliation of the medication history was
      attempted, using conventional methods, before accessing the EHR, and then the EHR
      was used to verify the reconciliation. In phase 2, the EHR was the initial method
      of retrieving the medication history-validated by conventional methods. RESULTS:
      : Where reconciliation was led by conventional methods, and before any access to
      the EHR was attempted, 28 (28%) of hospital prescriptions were found to contain
      errors. Of 99 prescriptions subsequently checked using the EHR, only 50 (50%)
      matched the EHR. Of the remainder, 25% of prescriptions contained errors when
      verified by the EHR. However, 26% of patients had an incorrect list of current
      medications on the EHR.Using the EHR as the primary method of reconciliation, 33
      (32%) of 102 prescriptions matched the EHR. Of those that did not match, 39 (38%)
      of prescriptions were found to contain errors. Furthermore, 37 (36%) of patients
      had an incorrect list of current medications on the EHR.The most common error
      type on the discharge prescription was drug omission; and on the EHR, wrong drug.
      Common potentially serious errors were related to unidentified allergies and
      adverse drug reactions. CONCLUSIONS: : The EHR can reduce medication errors.
      However, the EHR should be seen as one of a range of information sources for
      reconciliation; the primary source being the patient or their carer. Both primary
      care and hospital clinicians should have read-and-write access to the EHR to
      reduce errors at care transitions. We recommend further evaluation studies.

PMID- 21857239
TI  - Physicians' attitudes toward reporting medical errors-an observational study at a
      general hospital in Saudi Arabia.
AB  - OBJECTIVE: : Accurate medical error reporting is crucial for reducing the
      occurrence of such errors and their adverse consequences. This study aims to
      investigate the views of physicians about medical error reporting in a tertiary
      care hospital in Saudi Arabia. METHODS: : This is a cross-sectional self
      administrated survey study. All physicians in the hospital were invited to
      complete an anonymous survey questionnaire addressing demographic details, as
      well as attitudes, practice, and views on medical error reporting. RESULTS: : One
      hundred seven physicians completed the questionnaires (66.5% response rate). Mean
      (SD) age was 39.8 (9.0) years. One-fifth of the respondents worked in the
      emergency department, and half had a workload of 40 to 59 h/wk. The reason given
      by 41.1% for not reporting a medical error by a colleague was that "it is not
      their responsibility." However, the gravity of the outcome of a medical error by
      a colleague to the patient was thought to be an important incentive for
      reporting. Of the physicians, 43% agreed that they would conceal the occurrence
      of a medical error they incurred to "avoid punishment." Nevertheless, most of the
      respondents held the view that there exists an ethical underpinning for reporting
      medical errors and that reporting of medical errors serve a valuable purpose.
      CONCLUSIONS: : The physicians in our study are likely to disclose errors made by
      a colleague only if the error resulted in a severe damage to the patient, and as
      such, medical errors go underreported for a variety of reasons. It was felt that
      assurance of confidentiality and protection from backlash would promote medical
      error disclosure.

PMID- 21857240
TI  - Evaluation of time- and cost-saving modifications of HFMEA: an experimental
      approach in radiotherapy.
AB  - OBJECTIVE: : This study aimed to evaluate different shortcuts of Healthcare
      Failure Mode and Effects Analysis (HFMEA) in a radiotherapy setting. DESIGN: : A
      2 * 2 study design was set up, in which 4 similar groups analyzed separately the
      possible risks of the same process by using different versions of HFMEA. SETTING:
      : In the Maastricht Radiation Oncology clinic, a radiotherapy institute in the
      Netherlands, treatment of cancer patients is organized within 3 different units,
      each focusing on a specific area (thorax, abdomen, and neck-head). The institute
      plans to treat all radiation areas in one generalized unit (Linac-pool).
      PARTICIPANTS: : All 4 teams were composed of 3 radiation technologists (1 from
      each working unit), 1 manager radiation technologist, and 1 facilitator.
      INTERVENTIONS: : Prospective risk analyses were completed in parallel within 1
      month. MAIN OUTCOME MEASURES: : Time investment and cost data on the different
      steps of the HFMEAs were registered from the organizations' perspective. Each
      team suggested a number of corrective actions for the Linac-pool. The quality and
      feasibility of the proposed actions were assessed by an expert panel (managers
      and safety staff). RESULTS: : The HFMEA analyses resulted in direct costs varying
      from 1028.6 to 1701.6 euros. In total, the expert panel assessed 86 corrective
      actions, of which 43 (50%) were relevant to implement before the start of the
      Linac-pool. Many of these actions related to the compliance, control, and
      education of standard operating procedures in daily practice of radiotherapy.
      CONCLUSIONS: : On the basis of the results of this case study, it seems feasible
      to develop less time- and cost-consuming versions of HFMEA, which would increase
      even more the added value of prospective risk analysis tools for health care
      organizations.

PMID- 21857241
TI  - Preoperative surgical briefings do not delay operating room start times and are
      popular with surgical team members.
AB  - OBJECTIVES: : This study was carried out to evaluate the introduction of
      preoperative safety briefings on operating theater start times. In addition, we
      assessed staff attitudes toward the safety briefings. Lack of time, motivation,
      and a negative perception in staff are often cited as barriers to the
      implementation of safety briefings. METHODS: : The preoperative safety briefing
      consisted of a 5- to 10-minute meeting between anesthetic staff, surgeons, and
      nursing staff to discuss the operating list before the commencement of surgery.
      Using the hospital database, the operating theater start times were obtained for
      2 months before and after the introduction of the safety briefings. A
      questionnaire using a 5-point Likert scale was distributed to the operating room
      theater staff to evaluate attitudes toward the safety briefing. RESULTS: : There
      was no statistical difference in operating theater start time after the
      introduction of the safety briefing. The questionnaire responses from 37 theater
      staff demonstrated positive attitudes toward the safety briefings including
      agreeing strongly with factors affecting patient safety and communication. This
      included 97% replying that the safety briefing highlighted potential patient
      problems, whereas 89% believed it improved communication. CONCLUSIONS: : The
      safety briefings were popular among staff and did not delay the operating theater
      start time.

PMID- 21857242
TI  - Physicians-in-training attitudes on patient safety: 2003 to 2008.
AB  - OBJECTIVE: : Physician trainees will embody medicine's future culture. We assess
      whether trainees' patient safety attitudes have evolved over time. METHODS: : We
      anonymously surveyed more than 800 house staff and fourth-year medical students
      (MS 4) in 2008, at 1 academic institution, with a 19-item questionnaire and
      compared their responses to the 2003 responses at the same institution on the
      same questionnaire. RESULTS: : A total of 463 trainees (53%) completed the 2008
      survey, with a mean overall safety score of 3.54, which significantly improved
      from the 2003 overall score of 3.41 (P < 0.001). Compared with those from 2003,
      respondents in 2008 more strongly agree that physician-nurse teamwork (P =
      0.001), attending supervision (P = 0.017), 80-hour workweek (P < 0.001), computer
      order entry (P < 0.001), and improved resident sign-out (P < 0.001) help reduce
      adverse events. The 2008 trainees feel more prepared to prevent adverse events (P
      = 0.030) and more acknowledge the ethical responsibility to disclose adverse
      events to patients (P = 0.002). However, compared with 2003, fewer 2008
      respondents felt that reducing nurses' patient load would reduce adverse events
      (P = 0.015); on 8 questionnaire items, there were no significant attitudinal
      changes between 2003 and 2008. CONCLUSIONS: : Physician trainee safety attitudes
      at 1 institution improved between 2003 and 2008, and these trainees support many
      system-based solutions to adverse events. The changes seem incremental and
      responses do not fully align with all aspects of a safety culture. Cultural
      change in health care must involve trainees and address their attitudes.

PMID- 21857243
TI  - Are immunoglobulin A anti-gliadin antibodies helpful in diagnosing coeliac
      disease in children younger than 2 years?
AB  - The usefulness of immumoglobulin (Ig) A antibodies to gliadin (AGA-IgA) in
      addition to IgA anti-endomysium and tissue transglutaminase antibodies was
      evaluated in 4122 children younger than 2 years with a suspicion of coeliac
      disease (CD). Eight percent (312/4122) displayed IgA anti-endomysium and/or IgA
      anti-tissue transglutaminase, whereas 2.1% (85/4122) displayed only AGA-IgA.
      Clinical data were obtained for 62 of 85 children with isolated AGA-IgA, and 33
      children underwent a duodenal biopsy. Histologically proven CD was established
      for 5 patients, whereas 57 children were diagnosed to experience other diseases.
      The systematic detection of AGA-IgA using native gliadin conferred no additional
      diagnostic benefit for the diagnosis of CD in children younger than 2 years of
      age, except for rare cases.

PMID- 21857244
TI  - Midazolam-ketamine combination for moderate sedation in upper GI endoscopy.
AB  - OBJECTIVES: The aim of the study was to compare the quality of sedation with 3
      different sedation regimens in upper gastrointestinal endoscopy (UGIE) in
      pediatric patients. METHODS: One hundred fifty consecutive children who underwent
      UGIE were randomly assigned to 1 of the 3 medication regimens. Patients in group
      A (n = 49) received placebo. Forty-five minutes after the placebo was given,
      repeated intravenous (IV) doses of 0.1 mg/kg midazolam were administered titrated
      to achieve a level of deep sedation. Patients in group B (n = 51) received oral
      ketamine instead of placebo, and patients in group C (n = 50) received oral
      fentanyl instead of placebo with the same methodology and sedation endpoint.
      RESULTS: The mean dose of midazolam administered in group B patients was
      remarkably lower compared with that of groups A and C. Patients in group B showed
      less distress in IV line placement and separation from parents, higher comfort
      level, more endoscopist satisfaction, and higher sedation depth compared with
      groups A and C. The recovery time was significantly shorter in group B. All of
      the 3 regimens were safe. All of the complications were managed successfully.
      CONCLUSIONS: Our data suggest that synergistic sedation with oral ketamine and IV
      midazolam for UGIE in children is a suitable and safe sedation. The higher rate
      of vomiting in group B in contrast to previous studies must be caused mainly by
      the oral route of ketamine administration.

PMID- 21857245
TI  - Peritonitis after endoscopic caecostomy with a Chait Trapdoor catheter: what
      lessons can be learned?

PMID- 21857246
TI  - Comparison of quick point-of-care test for small-bowel hypolactasia with
      biochemical lactase assay in children.
AB  - AIM: The aim of the present study was to compare the Biohit Lactose Intolerance
      Quick Test (BLIQT) to the criterion standard biochemical duodenal lactase (DL)
      activity assay in the paediatric population using standard statistical
      comparative tests. METHODS: Using standard Olympus endoscopes, 2 postbulbar
      duodenal biopsies were taken from 38 prospective children (0-16 years) from June
      2008-May 2009 at a single tertiary paediatric gastroenterology unit. The biopsies
      were used for the BLIQT and for biochemical disaccharides assay. RESULTS: Thirty
      eight children (19 boys) of median age 5.45 years (0.3-14.8 years) underwent the
      combined BLIQT and disaccharidase testing. We subdivided the group into those who
      had biopsies with a larger endoscope (XQ, n = 26) and those who had a smaller
      endoscope (XP, n = 12) and thus a smaller biopsy forcep. When using a larger
      endoscope, the BLIQT showed a sensitivity of 100%, specificity of 86%, and
      positive and negative predictive value of 57.1% and 100%, respectively, on
      comparing it with DL. With a smaller endoscope, the BLIQT had a sensitivity of
      100%, specificity of 80%, positive predictive value of 50%, and a negative
      predictive value of 100%. CONCLUSIONS: As in adult studies, the sensitivity and
      negative predictive value of the BLIQT was 100%. The specificity too appears to
      be high but variable, probably because of smaller biopsies obtained, and may
      warrant the need for 2 biopsies. The high sensitivity, specificity, and negative
      predictive value of the BLIQT for indicating hypolactasia make it an effective
      point-of-care test for paediatric hypolactasia.

PMID- 21857247
TI  - Nutritional strategy for adolescents undergoing bariatric surgery: report of a
      working group of the Nutrition Committee of NASPGHAN/NACHRI.
AB  - Surgical options for the treatment of adolescent obesity have been gaining
      popularity. Adolescent patients present a particular challenge to clinicians,
      secondary to age-related issues, revolving around both mental and physical
      growth. These age-related issues require a unique approach to nutritional
      intervention for adolescents undergoing bariatric surgery as opposed to
      standardized approaches for adults. Despite the increasing numbers of adolescents
      undergoing obesity surgery, evidence-based nutritional guidelines have yet to be
      published. The goal of this document is to provide the clinician with
      recommendations on how to assess, educate, nourish, and monitor the adolescent
      who has undergone obesity surgery. A multidisciplinary panel composed of 3
      pediatric gastroenterologists, 1 psychologist, and 3 registered dietitians from
      the Nutrition Committee for the North American Society of Pediatric
      Gastroenterology, Hepatology, and Nutrition and National Association of
      Children's Hospitals and Related Institutions, with experience in nutrition and
      adolescent weight loss surgery, reviewed the medical literature for evidence
      based practice for nutritional strategies for patients undergoing bariatric
      surgery. In addition to this group, an adolescent medicine physician was
      consulted for matters related to reproductive health. The present article
      presents a consensus of recommendations based on a review of the literature. In
      areas for which there was a lack of evidence to support the recommendations, best
      practice guidelines were used. The present article provides the clinician with an
      overview of the nutritional concerns for adolescent patients undergoing obesity
      surgery. These guidelines address the preoperative educational pathway, the
      postoperative diet progression, recognition of disordered eating, guidelines for
      female reproductive issues, and assistance for the adolescent in a school/college
      environment.

PMID- 21857248
TI  - Diagnostic workup of paediatric patients with inflammatory bowel disease in
      Europe: results of a 5-year audit of the EUROKIDS registry.
AB  - OBJECTIVE: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the
      European Society for Pediatric Gastroenterology, Hepatology, and Nutrition
      published consensus guidelines on the diagnostic workup of paediatric IBD, the
      Porto criteria. According to these guidelines, children suspected of having IBD
      should undergo an oesophagogastroduodenoscopy (OGD), ileocolonoscopy, and (except
      in cases of definitive ulcerative colitis) adequate imaging of the small bowel.
      To audit and evaluate the diagnostic workup of paediatric patients with IBD in
      Europe, the Working Group created EUROKIDS, a prospective, Web-based registry of
      newly diagnosed paediatric patients with IBD. METHODS: Patients with IBD (ages 0
      18 years) were registered in 44 centres in 18 countries. Data on diagnostic
      workup were analysed according to the year of diagnosis, type of IBD, and centre
      size. Diagnostic yield of OGD and ileal intubation were evaluated. RESULTS:
      Between 2004 and 2009, 2087 newly diagnosed patients were correctly registered.
      Both OGD and ileocolonoscopy had been performed in 64% of all of the patients and
      increased significantly from year 1 (52 %) to 5 (71%, P  <  0.001). Small-bowel
      follow-through use decreased during the years (year 1 n = 213, year 5 n = 108; P
      < 0.001), whereas magnetic resonance imaging use increased (year 1 n  = 25, year
      5 n  = 171; P < 0.001). Patients diagnosed as having Crohn disease (CD, 59%) and
      ulcerative colitis (58%) were more likely to have had a complete diagnostic
      workup than patients diagnosed as having IBD unclassified (45%). In CD, the
      diagnostic yield of OGD was 7.5% and the yield of ileal intubation was 13%.
      CONCLUSIONS: The quality of diagnostic workup in paediatric patients with IBD
      increased steadily between 2004 and 2009. Small-bowel imaging by magnetic
      resonance imaging superseded the use of small-bowel follow-through. OGD and ileal
      intubation contributed to a definitive diagnosis of CD.

PMID- 21857249
TI  - Crohn disease: effect on children's lifestyles.
AB  - BACKGROUND AND AIM: Crohn disease (CD) presents a range of physical, social, and
      psychological challenges, and can adversely affect the quality of life of those
      affected by it. The present study aimed to investigate the health-related quality
      of life of paediatric patients with CD in the Wellington region. Measuring health
      related quality of life assists with resource allocation decisions and assesses
      various forms of interventions. METHODS: Patients ages 9 to 18 years with CD in
      the Wellington region were assessed using the IMPACT-III inflammatory bowel
      disease-specific questionnaire (n = 16). Eight participants filled it out and
      returned it by post; the remaining 8 filled it out in a meeting with the
      researcher and then underwent cognitive debriefing as part of a cross-cultural
      adaptation of the questionnaire. RESULTS: Of a maximum possible value of 175, the
      total health-related quality of life score had a mean value of 119.2 (standard
      deviation 30.7). Using Spearman rank correlation analysis, significant findings
      included a positive correlation between disease duration and quality of life (rho
      = 0.534, sig. <0.05) and a negative correlation between disease activity and
      quality of life (rho = -0.596, sig. <0.05). Qualitative information included
      difficulties in coping with long-term and unpleasant treatments and feelings of
      isolation. CONCLUSIONS: Children with Crohn disease in the Wellington region may
      benefit from age-specific social and psychological support. Because there is
      limited information on quality of life in young patients with CD in New Zealand,
      the results of the present study may be used as baseline data for future studies.

PMID- 21857250
TI  - Neutrophil transintestinal epithelial migration to CXCR2 ligands is regulated by
      adenosine.
AB  - OBJECTIVES: Polymorphonuclear leukocytes (PMN) feature prominently in the mucosa,
      including in crypt abscesses, of patients with inflammatory bowel disease, yet
      the mediators that are responsible for this migration are unknown. We discovered
      that CXCR2 chemokines (reportedly elevated in the mucosa) have reduced potency
      recruiting PMN across epithelial cell monolayers versus acellular filters, so the
      objective was to determine what molecules modify transepithelial PMN migration to
      CXCR2 chemokines. METHODS: Transwells with T84 colon carcinoma monolayers or no
      epithelium were used with adolescent patient peripheral blood PMN and CXCL8
      (interleukin-8 [IL-8], binds CXCR1 and CXCR2), CXCL5 (epithelial-derived
      neutrophil chemoattractant-78 [ENA-78]), or CXCL1 (Gro-alpha, both bind CXCR2) as
      chemoattractants. RESULTS: IL-8 was equally potent at recruiting PMN across
      filters and T84 monolayers growing on the filters. In contrast, ENA-78 and Gro
      alpha were significantly less potent at recruiting PMN across monolayers than
      across bare filters. Blocking CXCR1 reduced PMN migration across monolayers to IL
      8. We ruled out superoxide radicals possibly enhancing migration to IL-8 by using
      PMN from a patient with chronic granulomatous disease. PMN constitutively produce
      adenosine, so we added adenosine deaminase to the transwell assays and observed
      increased migration to ENA-78 across T84 monolayers. The level of migration was
      further enhanced by pretreating PMN with adenosine before adding the cells to the
      assay in the presence of the deaminase. CONCLUSIONS: PMN migration mediated by
      CXCR2 through the epithelium is regulated by adenosine. Adenosine appears to
      reduce transepithelial migration by influencing beta2 integrin use on the PMN.

PMID- 21857251
TI  - Glycogen storage disease type IX: novel PHKA2 missense mutation and cirrhosis.

PMID- 21857252
TI  - Multicomponent school-initiated obesity intervention in a high-risk, Hispanic
      elementary school.
AB  - The aim of the study was to determine the effectiveness of a school-initiated
      cognitive and behavioral program to reduce childhood obesity. Height, weight,
      body mass index (BMI), and BMI z scores were obtained at the beginning and end of
      the school year at an intervention school (n = 1022) and at a control school (n =
      692). The prevalence of overweight and obesity was 18.9% and 30.4% versus 19% and
      30.2%, respectively, in the intervention and control schools. The incidence of
      overweight increased in the control school, but the incidence of obesity, weight,
      and BMI z scores increased significantly in the intervention school, suggesting
      that implementation of any school-based obesity intervention programs requires
      careful planning to achieve goals.

PMID- 21857253
TI  - Comparison of demographic characteristics, surgical resection patterns, and
      survival outcomes for veterans and nonveterans with non-small cell lung cancer in
      the Pacific Northwest.
AB  - INTRODUCTION: Lung cancer is a leading cause of death in the United States and
      among veterans. This study compares patterns of diagnosis, treatment, and
      survival for veterans diagnosed with non-small cell lung cancer (NSCLC) using a
      recently established cancer registry for the Veterans Affairs Pacific Northwest
      Network with the Puget Sound Surveillance, Epidemiology, and End Results cancer
      registry. METHODS: A cohort of 1715 veterans with NSCLC were diagnosed between
      2000 and 2006, and 7864 men were diagnosed in Washington State during the same
      period. Demographics, tumor characteristics, initial surgical patterns, and
      survival across the two registries were evaluated. RESULTS: Veterans were more
      likely to be diagnosed with stage I or II disease (32.8%) compared with the
      surrounding community (21.5%, p = 0.001). Surgical resection rates were similar
      for veterans (70.2%) and nonveterans (71.2%) older than 65 years with early-stage
      disease (p = 0.298). However, veterans younger than 65 years with early-stage
      disease were less likely to undergo surgical resection (83.3% versus 91.5%, p =
      0.003). Because there were fewer late-stage patients among veterans, overall
      survival was better, although within each stage group veterans experienced worse
      survival compared with community patients. The largest differences were among
      early-stage patients with 44.6% 5-year survival for veterans compared with 57.4%
      for nonveterans (p = 0.004). CONCLUSIONS: The use of surgical resection among
      younger veterans with NSCLC may be lower compared with the surrounding community
      and may be contributing to poorer survival. Cancer quality of care studies have
      primarily focused on patients older than 65 years using Medicare claims; however,
      efforts to examine care for younger patients within and outside the Department of
      Veterans Affairs are needed.

PMID- 21857254
TI  - A comprehensive analysis of p16 expression, gene status, and promoter
      hypermethylation in surgically resected non-small cell lung carcinomas.
AB  - INTRODUCTION: The role of p16 is gaining importance in non-small cell lung cancer
      (NSCLC) because of epigenetic therapy options. Further insight into the
      significance of protein expression, gene status and promoter methylation is
      needed and has the potential to optimize existing treatment strategies. METHODS:
      This population-based study analyzes p16 in 383 surgically resected non-small
      cell lung carcinomas brought into a standardized tissue microarray platform.
      Immunohistochemistry and fluorescence in situ hybridization were performed. For
      selected cases, p16 promoter hypermethylation was assessed by a pyrosequencing
      assay. Extensive clinical data and a postoperative follow-up period of 15 years
      enabled detailed correlations. RESULTS: Loss of p16 expression is a common event
      in NSCLC (232/365, 64%), especially in squamous cell carcinomas (97/115, 84%) in
      contrast to adenocarcinomas (93/186, 50%). Loss of p16 expression was associated
      with poorer survival time for the entire cohort and for certain subgroups
      including men, age younger than 65 years, smokers, early tumor stage,
      adenocarcinoma, and large-cell carcinoma. Promoter hypermethylation was absent
      for cases expressing p16 but was commonly observed when (heterozygous) p16 gene
      deletions were present and in cases negative for p16. CONCLUSION: Our
      comprehensive data would be compatible with a two-step process leading to loss of
      p16 expression in NSCLC. Hypermethylation of the promoter region may represent an
      early event, followed by heterozygous deletion of the p16 locus. Because of the
      possibility of detection of hypermethylated gene regions, these data may lead to
      the identification of specific patient subgroups more likely to benefit from
      upcoming demethylating treatment strategies.

PMID- 21857255
TI  - Annual pediatric pedestrian education does not improve pedestrian behavior.
AB  - BACKGROUND: Pediatric pedestrian injuries are a major health care concern,
      specifically in urban centers. An educational program (WalkSafe), given one time
      during the school year, has been shown to improve childhood pedestrian safety. We
      examined whether this program could create similar long-term cognitive and
      behavioral changes in our school-aged children. METHODS: An established pediatric
      pedestrian curriculum was modified slightly for use in our area. Students K
      fourth grade were exposed to the program once annually for 2 years. The program
      was carried out weekly for 3 consecutive weeks. The first and third sessions
      consisted of an educational module given by the classroom teacher. The second
      week consisted of an interactive assembly that allowed the children to
      demonstrate good pedestrian safety using a simulated street. Short- and
      intermediate-term cognitive knowledge was evaluated using standardized pre-, post
      and 3-month follow-up tests. Long-term knowledge was assessed by comparing
      scores as students advanced in grade from year 1 to 2 of the program (K to first,
      first to second, etc.). At six schools during year 2, pedestrian behavior was
      measured through direct observation of children on city streets before and after
      administering the program. The project was approved by university and school
      board institutional review boards. RESULTS: During the 2 years, 1,564 students
      from nine schools were educated. In both years of the program, students in all
      grades had a significant gain in test scores immediately after and at 3 months
      compared with baseline knowledge. In contrast, only students moving from grade 3
      to 4 demonstrated long-term retention (K->1: 7.7 vs. 6.7; grade 1->2: 7.8 vs.
      6.7; grade 2->3: 7.3 vs. 6.8; grade 3->4: 7.1 vs. 8.0; all p < 0.05 year 2
      pretest vs. year 1 3-month posttest; analysis of variance and generalized linear
      model). Only 30% of children walk with an adult. Direct observation showed 64% of
      children stopped at the curb but only 8% looked left-right-left. Children walking
      alone were more likely to cross mid-block compared with those walking with an
      adult (12% vs. 3%; p < 0.001) and also tend to look left-right-left significantly
      more than those walking with an adult (67% vs. 20%; p < 0.0001). CONCLUSIONS: A
      one-time annual educational program resulted in long-term knowledge retention
      between grades 3 and 4 only. In contrast, scores in younger grades reverted to
      baseline pretest values seen in year 1. Short- and intermediate-term knowledge
      gains were seen in all grades for both years. Because older children more often
      walk alone, we postulate that the improved retention may be the result of
      repeated exposure and practice as a pedestrian. Cognitive knowledge did not
      appear to translate into improved pedestrian behavior. Walking with an adult also
      had a negative impact on observed pedestrian safety behavior. The efficacy and
      impact of a one-time educational program may be insufficient to change long-term
      behavior and must be reevaluated.

PMID- 21857256
TI  - Blunt pulmonary contusion: admission computed tomography scan predicts mechanical
      ventilation.
AB  - BACKGROUND: Blunt pulmonary contusion (BPC) evolves over 12 to 24 hours, and the
      initial plain radiographs fail to reliably identify patients at risk of clinical
      deterioration. Admission computed tomography (CT) may offer accurate
      characterization of BPC and early prediction of the need for mechanical
      ventilation (MV). METHODS: This was a combination of a 5-year retrospective study
      (January 2002 to April 2007) and a 6-month prospective study (September 2007 to
      February 2008) of adult blunt trauma (BT) patients with thoracic injuries and a
      chest CT upon hospital arrival. The primary outcome was MV due to thoracic
      trauma. To ensure that MV was required for BPC and not for associated injuries,
      all patients with significant extrathoracic injuries (Abbreviated Injury Scale
      score >2) were excluded. The extent of BPC was measured by two scoring systems.
      RESULTS: Of 392 patients (67% males; age, 48 years +/- 21 years; Abbreviated
      Injury Scale score chest, 3 +/- 1; and Injury Severity Score [ISS], 13 +/- 6),
      243 (62%) had BPC. Twenty-five (6%) patients required MV and two (0.5%) died. The
      combination of Glasgow Coma Scale (GCS) score <14, BPC score >2, and >4 ribs
      fractured predicted MV in 100% of the cases, and the absence of all factors
      precluded MV in 100%. In the prospective period of 6 months, 55 patients had BPC
      and we confirmed our finding that the absence of the three factors precludes MV.
      CONCLUSION: A simple score derived by the initial chest CT, in combination with
      GCS and the number of fractured ribs, can predict the need for MV early. In the
      presence of these predictors, patients should be admitted to a high level of
      monitoring.

PMID- 21857258
TI  - Utility of repeat head computed tomography in patients with an abnormal
      neurologic examination after minimal head injury.
AB  - BACKGROUND: Previous studies proposed that repeat head computed tomography (RHCT)
      is of no value in patients with a minimal head injury (MHI) and normal neurologic
      examination (NE). The goal of our study was to investigate the value of RHCT in
      patients with MHI with an abnormal NE. METHODS: A retrospective chart review of
      adult patients presenting to a Level I trauma center from July 2002 to December
      2006 with MHI was performed. Demographics, injury severity, and HCT findings were
      collected. Patients with an abnormal NE at the time of RHCT were divided into
      three subgroups: acute deterioration NE (AD-NE), persistently abnormal NE (PA
      NE), and unknown NE (U-NE). Changes in the management and outcomes after RHCT
      were compared. RESULTS: One hundred seven patients had a MHI with an abnormal NE.
      Of those, seven (6.5%) had a change in management after RHCT. At the time of
      RHCT, 68 patients (63%) had a PA-NE, 21 AD-NE, and 18 U-NE. Six patients (29%)
      with AD-NE, 1 patient (6%) with an U-NE, and no patients with PA-NE required
      changes in management after RHCT. Compared with a RHCT, NE had higher positive
      and negative predictive values in determining the need for management changes.
      CONCLUSIONS: Of all patients with MHI with an abnormal NE at the time of RHCT,
      63% had a PA-NE. Although a RHCT is beneficial to patients with an acutely
      deteriorating or U-NE, it appears to be of little value in patients with a PA-NE.
      Compared with RHCT, serial NE may be a stronger predictor for the need for
      intervention in patients with MHI.

PMID- 21857260
TI  - Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after
      blunt chest trauma-induced lung contusion in mice.
AB  - BACKGROUND: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated
      or aggravated lung injury. Therefore, we tested the hypothesis whether
      posttreatment intravenous Na2S (sulfide) may attenuate lung injury. METHODS:
      After blast wave blunt chest trauma or sham procedure, anesthetized and
      instrumented mice received continuous intravenous sulfide or vehicle while being
      kept at 37 degrees C or 32 degrees C core temperature. After 4 hours of pressure
      controlled, thoracopulmonary compliance-titrated, lung-protective mechanical
      ventilation, blood and tissue were harvested for cytokine concentrations, heme
      oxygenase-1, IkappaBalpha, Bcl-Xl, and pBad expression (western blotting),
      nuclear factor-kappaB activation (electrophoretic mobility shift assay), and
      activated caspase-3, cystathionine-beta synthase and cystathionine-gamma lyase
      (immunohistochemistry). RESULTS: Hypothermia caused marked bradycardia and
      metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary
      compliance and arterial Po2, again without sulfide effect. Cytokine levels showed
      inconsistent response. Sulfide increased nuclear factor-kappaB activation during
      normothermia, but this effect was blunted during hypothermia. While histologic
      lung injury was variable, both sulfide and hypothermia attenuated the trauma
      related increase in heme oxygenase-1 expression and activated caspase-3 staining,
      which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide
      and hypothermia also attenuated the trauma-induced cystathionine-beta synthase
      and cystathionine-gamma lyase expression. CONCLUSIONS: Posttreatment sulfide
      infusion after blunt chest trauma did not affect the impaired lung mechanics and
      gas exchange but attenuated stress protein expression and apoptotic cell death.
      This protective effect was amplified by moderate hypothermia. The simultaneous
      reduction in cystathionine-beta synthase and cystathionine-gamma lyase expression
      supports the role of H2S-generating enzymes as an adaptive response during stress
      states.

PMID- 21857261
TI  - Leptin relieves intestinal ischemia/reperfusion injury by promoting ERK1/2
      phosphorylation and the NO signaling pathway.
AB  - BACKGROUND: Recently, research has indicated that leptin plays a protective role
      in traumatic brain and liver injury. We studied the protective effect of leptin
      on intestinal I/R injury and examined its mechanism by using mice intestinal I/R
      model and murine peritoneal macrophage hypoxia/reoxygenation (H/R) injury model.
      METHODS: Leptin was intraperitoneally administrated at 45 minutes after ischemia,
      then reperfusion for two hours. Cells were treated with different concentrations
      of leptin at three hours after hypoxia, then reoxygenation for six hours. Mice
      intestines were harvested for histopathologic properties. The malondialdehyde,
      nitric oxide (NO), interleukin-6, and total antioxidative capacity were detected
      according to respective assay kit. Phosphorylated extracellular regulated
      kinase1/2 (p-ERK1/2) and phosphorylated cytosolic phospholipase A(2) (p-cPLA2)
      were determined by Western blot assay. RESULTS: Here, we show that leptin reduced
      intestinal histologic alterations, malondialdehyde and interleukin-6 levels but
      increased the endogenous leptin expression and NO production in the intestines.
      Leptin also increased the NO and total antioxidative capacity levels in cells. We
      further demonstrated that leptin markedly activated ERK1/2 in the intestines and
      activated ERK1/2 and cPLA2 in the cells. Moreover, the protective effect of
      leptin against intestinal I/R injury and elevated NO production was attenuated by
      blocking the ERK1/2 pathway. CONCLUSIONS: These data demonstrate that leptin
      ameliorated intestinal I/R and peritoneal macrophage H/R injury by enhancing
      ERK1/2 phosphorylation and promoting the NO production signaling pathway.

PMID- 21857262
TI  - Mycoplasma pneumoniae and respiratory virus infections in children with
      persistent cough in England: a retrospective analysis.
AB  - BACKGROUND: Persistent cough following an acute respiratory tract infection is
      common in children, but clinicians may find it difficult to give accurate
      prognostic information on likely duration of cough without a microbiologic
      diagnosis. This study estimates the prevalence of Mycoplasma pneumoniae (Mp) and
      assesses the prognostic value of detecting Mp and respiratory viruses in children
      with persistent cough. METHODS: We retrospectively analyzed blood samples,
      nasopharyngeal aspirates (NPAs), and cough duration data from 179 children with
      persistent cough lasting 14 days or longer. Of these children, 37% had
      serologically confirmed Bordetella pertussis (pertussis). We detected Mp by
      polymerase chain reaction of NPAs and IgM serology, and respiratory viruses
      (human rhinoviruses, influenza viruses, respiratory syncytial viruses, and human
      metapneumovirus) by polymerase chain reaction of NPAs. We used Kaplan-Meier
      analyses to calculate median cough durations with 95% confidence intervals (CIs).
      RESULTS: We detected Mp in 22 of 170 children with sufficient blood and/or NPAs
      (12.9%, 95% CI: 8.7-18.8). Cough duration in children with positive Mp serology
      (median: 39 days, 95% CI: 24-54) was significantly shorter than in children with
      positive pertussis serology (median: 118 days, 95% CI: 82-154, P < 0.001). The
      presence of respiratory viruses did not significantly lengthen cough duration in
      children with pertussis (median: 154 days, 95% CI: 74-234, P = 0.810). Only 3
      children had both Mp and respiratory virus infections. CONCLUSIONS: Mp is an
      important infection in children with persistent cough and is associated with a
      significantly shorter duration of cough than pertussis. However, detecting
      respiratory viruses does not add prognostic value in children with pertussis.

PMID- 21857263
TI  - Influenza Beta/Victoria antigen induces strong recall of Beta/Yamagata but lower
      Beta/Victoria response in children primed with two doses of Beta/Yamagata.
AB  - OBJECTIVES: Trivalent inactivated influenza vaccine (TIV) contains 1 of 2
      influenza B/lineages (B/Yamagata or B/Victoria) annually. We assessed prime-boost
      responses in young children following a change in the B/lineage included in TIV.
      METHODS: Participants were primed during a clinical trial as infants or toddlers
      with two 0.25 or two 0.5 mL doses of 2008-2009 TIV containing
      B/Florida/4/06(Yamagata) antigen. In subsequent years, sequential subsets
      received annual age-appropriate doses of 2009-2010 and 2010-2011 TIV containing
      the changed influenza B/lineage antigen (B/Brisbane/60/08(Victoria)). Serologic
      response was assessed pre- and postimmunization by hemagglutination inhibition
      (HI; with/without ether treatment of influenza B antigen) and
      microneutralization. The primary immunogenicity outcome was the seroprotection
      rate (SPR) measured by HI without ether treatment (SPR:HI titers >=40). RESULTS:
      Fifty-six children were included in 2009-2010 and 36 in 2010-2011 analyses.
      Before the 2009-2010 TIV dose, antibody to all 2008-2009 TIV components had
      fallen to low levels: SPR <10% for B/Florida/4/06(Yamagata) and
      B/Brisbane/60/08(Victoria) antigens. A single 2009-2010 TIV dose boosted antibody
      to the shared 2008-2009/2009-2010 influenza A antigens and to the priming 2008
      2009 B/Florida/4/06(Yamagata) antigen with SPRs >85%. In contrast, antibody to
      the B/Brisbane/60/08(Victoria) antigen included in the 2009-2010 TIV remained
      low: SPR <25%. Antibody to the B/Brisbane/60/08(Victoria) antigen was not
      improved from a further dose in the 2010-2011 TIV: SPR 31% versus SPR 69% to
      B/Yamagata. A similar pattern of B/Yamagata dominance was observed when HI
      testing was conducted with antigen prepared by ether treatment. CONCLUSIONS:
      Repeated annual TIV doses containing B/Victoria-lineage antigen strongly recalled
      antibodies to the B/Yamagata antigen of first exposure, but elicited lower
      B/Victoria responses.

PMID- 21857264
TI  - Systematic review on the etiology and antibiotic treatment of pneumonia in human
      immunodeficiency virus-infected children.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity
      and mortality in human immunodeficiency virus (HIV)-infected children. OBJECTIVES
      AND METHODS: A systematic review of studies that were published between January
      1990 and February 2009 on the etiology and antimicrobial or adjunctive systemic
      management of CAP in HIV-infected children. RESULTS: Pneumocystis jirovecii had
      the strongest association with HIV infection, with a summary odds ratio of 10.1
      (95% confidence interval [CI], 17.7-62.1) and 9.1 (95% CI, 2.5-33.1) in
      antemortem and postmortem studies, respectively. Cytomegalovirus was strongly
      associated with HIV positivity among fatal cases of pneumonia (summary odds ratio
      = 14.4 [95% CI, 6.7-30.8]). There was a trend toward a greater prevalence of
      Staphylococcus aureus (odds ratio, 2.5; 95% CI, 0.95-6.4) in HIV-infected
      children. Major limitations identified included substantial methodological
      heterogeneity across studies, limited sensitivity of assays for diagnosing
      bacterial pneumonia, and studies primarily being undertaken in the absence of
      antiretroviral treatment or cotrimoxazole prophylaxis. No a priori-planned
      randomized controlled trials on antimicrobial management of CAP in HIV-infected
      children were identified. CONCLUSIONS: A World Health Organization panel used
      this review as well as analysis of risks and benefits to revise recommendations
      for antimicrobial treatment of CAP. Ampicillin plus gentamicin or ceftriaxone is
      now recommended as first-line empiric regimens for treating severe and very
      severe CAP in HIV-infected children. In addition, treatment with cloxacillin or
      vancomycin is recommended in settings with a high incidence of methicillin
      resistant S. aureus, and particularly if clinical or microbiological evidence of
      S. aureus pneumonia exist. Further studies in HIV-infected children on CAP
      etiology and antibiotic treatment are required in the era of antiretroviral
      treatment.

PMID- 21857265
TI  - Patient experiences as knowledge for the evidence base: a qualitative approach to
      understanding patient experiences regarding the use of regional anesthesia for
      hip and knee arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: It is reported that patients continue to have
      misgivings about regional anesthesia (RA) despite strong evidence to support its
      use for hip and knee replacement surgery. To date, no one has had an opportunity
      to study the experiences of patients who have undergone both types of anesthesia
      for these procedures. METHODS: Using descriptive qualitative methods, 12 patients
      who had hip or knee replacements under both RA and GA at two different time
      points (excluding revisions) were interviewed using purposeful sampling until
      saturation had been reached. Following transcription of each tape, a small study
      team met over the course of several months to read and discuss each transcript. A
      coding template was developed, and emerging themes noted. RESULTS: For the
      majority of patients, RA was either well tolerated or preferred. Having a
      previous negative experience with general anesthesia was common and was strongly
      associated with a patient's satisfaction with RA. Patients also described being
      highly influenced by the preference of their surgeon. CONCLUSIONS: These findings
      have important implications. First, many patients were surprisingly neutral about
      the procedure and seemed more fearful of anesthesia in general rather than of
      either technique specifically. This finding, combined with patient's influence by
      clinician preference, underscores the importance of physician support for RA.
      Some participants identified one of their misgivings about RA as being fear of
      being awake, which is consistent with the medical literature. Our findings also
      support the idea that from a patient's perspective, appropriate sedation while
      undergoing RA may be important.

PMID- 21857266
TI  - Is sciatic nerve block advantageous when combined with femoral nerve block for
      postoperative analgesia following total knee arthroplasty? A systematic review.
AB  - Sciatic nerve block (SNB) is commonly performed in combination with femoral nerve
      block (FNB) for postoperative analgesia following total knee arthroplasty (TKA).
      This systematic review examines the effects of adding SNB to FNB for TKA compared
      with FNB alone on acute pain and related outcomes. Four intermediate-quality
      randomized and 3 observational trials, including a total of 391 patients, were
      identified. Three of 4 trials investigating the addition of single-shot SNB and 2
      of 3 trials investigating continuous SNB reported improved early analgesia at
      rest and reduced early opioid consumption. Only 2 trials specifically assessed
      posterior knee pain. We were unable to uncover any clinically important analgesic
      advantages for SNB beyond 24 hours postoperatively. At present, there is
      inconclusive evidence in the literature to define the effect of adding SNB to FNB
      on acute pain and related outcomes compared with FNB alone for TKA.

PMID- 21857267
TI  - Stroke, regional anesthesia in the sitting position, and hypotension: a review of
      4169 ambulatory surgery patients.
AB  - BACKGROUND AND OBJECTIVE: Intraoperative hypotension is used to reduce surgical
      bleeding. Case reports of stroke after general anesthesia in the sitting position
      led us to collect data (patient demographics, medical risk factors for stroke,
      intraoperative hemodynamics) about the incidence of stroke after surgery in the
      sitting position. METHODS: This study reviewed 4169 (3000 retrospective, 1169
      prospective) ambulatory shoulder surgeries in the sitting position. For the
      prospective cohort, patients were queried postoperatively regarding stroke, with
      corroboration from 4 databases (anesthesia department quality assurance, hospital
      case management, state-reportable events, and hospital information system
      diagnostic code databases). For the retrospective cohort, rate of stroke was
      determined via the same 4 databases. RESULTS: No patient had a stroke (95%
      confidence interval, 0%-0.07%). Risk factors for perioperative stroke were
      present in 40% of patients. Brachial plexus nerve block with intravenous sedation
      was used for 95.7% (retrospective) and 99.8% (prospective) of the cohorts. Many
      patients (47%) experienced intraoperative hypotension by at least one definition:
      40% (retrospective) and 30% (prospective) had at least a 30% decrease in mean
      arterial pressure; 27% (retrospective) and 24% (prospective) had a mean pressure
      less than 66 mm Hg; and 13% (retrospective) and 12% (prospective) had a systolic
      blood pressure of less than 90 mm Hg. CONCLUSIONS: No strokes were observed in
      4169 patients. The estimated upper limit of the 95% confidence interval for
      stroke after regional anesthesia for shoulder surgery in the seated position is
      0.07%, despite frequent incidence of hypotension.

PMID- 21857268
TI  - Catheter orifice configuration influences the effectiveness of continuous
      peripheral nerve blockade.
AB  - BACKGROUND AND OBJECTIVES: We investigated perineural catheter threading distance
      and orifice configuration during continuous interscalene analgesia. METHODS: One
      hundred fifty-three patients receiving an anterolateral interscalene catheter
      (catheter needle and nerve/plexus in a similar alignment) for elective shoulder
      surgery were randomized to 1 of 3 groups: following out-of-plane ultrasound
      confirmation of the needle tip immediately lateral to the C5/6 roots, a
      nonstimulating catheter was blindly advanced 0.5 cm (end-hole; n = 50), 2.5 cm
      (multiorifice; n = 50) or 5 cm (multiorifice; n = 53) beyond the needle tip.
      Ropivacaine 0.75% + lidocaine 1% (50:50) 20 mL was administered preoperatively
      via the catheter before surgery under general anesthesia. A ropivacaine 0.2% 2
      mL/hr elastomeric infusion with mandatory 6 hourly (and on demand) 5-mL boluses
      was continued for more than 48 hrs with tramadol available as rescue. Patients
      were questioned in the recovery room, at 24 and 48 hrs for numerical rating pain
      score (0-10), ropivacaine bolus, and tramadol consumption. RESULTS: Patients were
      more frequently pain-free in the recovery room in the multiorifice 2.5 and 5 cm
      groups compared with the end-hole 0.5 cm group (94%, 91% vs 66%; P < 0.001).
      During the first 24 hrs, the end-hole group demonstrated an earlier time to first
      pain (median, 10 vs17, 15 hrs; P < 0.001), higher "average pain" (median, 3 vs 1,
      2, P = 0.004), and more ropivacaine bolus (median, 5 vs 3, 3; P < 0.001) and
      tramadol consumption (P = 0.01). Groups 2.5 and 5 cm did not significantly differ
      in any outcomes. CONCLUSIONS: These results suggest that multiorifice catheters
      provide superior intermittent bolus continuous peripheral nerve blockade compared
      with end-hole catheters. For anterolateral approach interscalene catheter
      placement, there is minimal benefit, either way, to 2.5- or 5-cm blind catheter
      advancement.

PMID- 21857269
TI  - Retained stimulating perineural catheters: a report of four cases.
AB  - BACKGROUND: As the use of ambulatory continuous peripheral nerve blocks continues
      to grow, new management issues will inevitably arise. Previous descriptions of
      difficult catheter removal due to cutting, knotting, or kinking of the catheter
      have involved inpatients. A series of retained ambulatory interscalene catheters
      has recently been reported. METHODS: We present a series of 4 retained
      stimulating perineural catheters, which could not be removed though the catheters
      appeared intact and not significantly bent on plain radiographs. We discuss the
      potential aspects of our block technique and the catheters' design that may have
      complicated their removal, as well as our management of these patients.
      CONCLUSIONS: Stimulating perineural catheters may be difficult to remove. This
      may be particularly problematic for outpatients removing the catheters at home.

PMID- 21857270
TI  - Proactive error analysis of ultrasound-guided axillary brachial plexus block
      performance.
AB  - BACKGROUND: Detailed description of the tasks anesthetists undertake during the
      performance of a complex procedure, such as ultrasound-guided peripheral nerve
      blockade, allows elements that are vulnerable to human error to be identified. We
      have applied 3 task analysis tools to one such procedure, namely, ultrasound
      guided axillary brachial plexus blockade, with the intention that the results may
      form a basis to enhance training and performance of the procedure. METHODS: A
      hierarchical task analysis of the procedure was performed with subsequent
      analysis using systematic human error reduction and prediction approach (SHERPA).
      Failure modes, effects, and criticality analysis was applied to the output of our
      SHERPA analysis to provide a definitive hierarchy to the error analysis. RESULTS:
      Hierarchical task analysis identified 256 tasks associated with the performance
      of ultrasound-guided axillary brachial plexus blockade. Two hundred twelve
      proposed errors were analyzed using SHERPA. Failure modes, effects, and
      criticality analysis methodology was applied to the output of SHERPA analysis to
      prioritize 20 errors. CONCLUSIONS: This study presents a formal analysis of (i)
      the specific tasks that might be associated with the safe and effective
      performance of the procedure and (ii) the most critical errors likely to occur as
      trainees learn to perform the procedure. Potential applications of these data
      include curricular development and the design of tools to teach and assess block
      performance.

PMID- 21857271
TI  - Glutamate release and neurologic impairment after intrathecal administration of
      lidocaine and bupivacaine in the rat.
AB  - BACKGROUND: Local anesthetic-induced neurotoxicity is one of the potential causes
      of postspinal anesthesia neurologic injury. Many experimental and clinical
      studies have demonstrated that lidocaine is more neurotoxic than bupivacaine. The
      mechanisms of local anesthetic-induced neurotoxicity remain unclear. Glutamate is
      an excitatory amino acid and widely exists in the central nervous system.
      Overstimulation of the glutamate receptors may produce neuronal toxic effect. In
      this study, we used in vivo microdialysis to examine the glutamate release in
      cerebrospinal fluid (CSF) after intrathecal lidocaine and bupivacaine injection.
      METHODS: Male Wistar rats were used. Administration of lidocaine (5 groups:
      normal saline, 2.5%, 5%, 10%, and 10% + MK-801 intrathecally injected) and
      bupivacaine (4 groups: normal saline, 0.25%, 0.5%, and 1% intrathecally injected)
      was performed in both microdialysis and postinjection neurologic sequelae
      studies. After intrathecal injection of the studied agents, the CSF dialysates
      were collected in 10-minute intervals for 2 hours. Cerebrospinal fluid glutamate
      concentrations were measured by high-performance liquid chromatography. In
      addition, tail-flick latencies were examined daily before and after microdialysis
      for 4 days. RESULTS: Intrathecal lidocaine concentration-dependently elevated
      glutamate release in CSF. Pretreatment with MK-801 significantly inhibited the
      glutamate release induced by 10% lidocaine. Intrathecal bupivacaine has no
      influence on glutamate release in CSF. The tail-flick latencies were
      significantly prolonged for 4 days after intrathecal lidocaine injection, and
      these effects were in a concentration-dependent manner. Pretreatment with MK-801
      significantly reversed the 10% lidocaine-induced prolonged tail-flick latencies.
      There was no difference of the tail-flick latencies among the bupivacaine-treated
      groups. CONCLUSIONS: Intrathecal lidocaine caused a concentration-dependent
      increase of the CSF glutamate release and postinjection neurologic impairment;
      these effects can be reversed by MK-801. However, intrathecal bupivacaine shows
      no influence. We suggest that glutamate may be involved in the pathogenesis of
      lidocaine-induced spinal neurotoxicity.

PMID- 21857272
TI  - Local anesthetic Schwann cell toxicity is time and concentration dependent.
AB  - BACKGROUND: Peripheral nerve blocks with local anesthetics (LAs) are commonly
      performed to provide surgical anesthesia or postoperative analgesia. Nerve injury
      resulting in persistent numbness or weakness is a potentially serious
      complication. Local anesthetics have previously been shown to damage neuronal and
      Schwann cells via several mechanisms. We sought to test the hypothesis that LAs
      are toxic to Schwann cells and that the degree of toxicity is directly related to
      the concentration of LA and duration of exposure. Intraneural injection of LAs
      has been shown to produce nerve injury. We sought to test the hypothesis that a
      prolonged extraneural infusion of LA can also produce injury. METHODS: Schwann
      cells cultured from neonatal rat sciatic nerves were incubated with LAs at
      different concentrations (10, 100, 500, and 1000 MUM), and each concentration was
      assessed for toxicity after 4, 24, 48 and 72 hours of exposure. Local anesthetics
      tested were lidocaine, mepivacaine, chloroprocaine, ropivacaine, and bupivacaine.
      Cell death was assessed by lactate dehydrogenase release measured by optical
      density.In a separate experiment, a microcatheter was placed along the sciatic
      nerves of Sprague-Dawley rats. Rats were randomly assigned to receive either 0.9%
      saline (n = 8) or bupivacaine (0.5%, n = 4; 0.75%, n = 4) via the perineural
      catheters for 72 hours. The rats were then killed, and their nerves sectioned and
      stained for analysis. Sections were stained for myelin and with an antimacrophage
      (CD68) antibody. RESULTS: None of the LAs tested produced significant Schwann
      cell death at very low concentrations (10 MUM, or 0.0003%) even after prolonged
      exposure. With prolonged exposure (48 or 72 hrs) to high concentrations (1000
      MUM, or 0.03%), all of the LAs tested produced significant Schwann cell death
      (increased lactate dehydrogenase release relative to control as measured by
      optical density, 0.384-0.974; all P values < 0.001). Only bupivacaine produced
      significant cell death (0.482, P < 0.001) after prolonged exposure to low
      concentrations (100 MUM, or 0.003%). At intermediate concentrations (500 MUM, or
      0.015%), cell death was more widespread with bupivacaine (0.768, P < 0.001) and
      ropivacaine (0.675, P < 0.001) than the other agents (0.204-0.368; all P values <
      0.001). Prolonged extraneural exposure of rat sciatic nerves to bupivacaine
      caused significant demyelination and infiltration of nerves with inflammatory
      cells. CONCLUSIONS: Local anesthetics induce Schwann cell death in a time- and
      concentration-dependent manner. Bupivacaine and ropivacaine have greater toxicity
      at intermediate concentrations, and prolonged exposure to bupivacaine produces
      significant toxicity even at low concentrations. Brief exposure to high
      concentrations of bupivacaine damages Schwann cells. Prolonged extraneural
      infusion of bupivacaine results in nerve injury.

PMID- 21857273
TI  - Value of single-injection or continuous sciatic nerve block in addition to a
      continuous femoral nerve block in patients undergoing total knee arthroplasty: a
      prospective, randomized, controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Continuous femoral nerve block in patients undergoing
      total knee arthroplasty (TKA) improves and shortens postoperative rehabilitation.
      The primary aim of this study was to investigate whether the addition of sciatic
      nerve block to continuous femoral nerve block will shorten the time-to-discharge
      readiness. METHODS: Ninety patients undergoing TKA were prospectively randomized
      to 1 of 3 groups: patient-controlled analgesia via femoral nerve catheter alone
      (F group) or combined with a single-injection (Fs group) or continuous sciatic
      nerve block (FCS group) until the second postoperative day. Discharge readiness
      was defined as the ability to walk and climb stairs independently, average pain
      on a numerical rating scale at rest lower than 4, and no complications. In
      addition, knee function, pain, supplemental morphine requirement, local
      anesthetic consumption, and postoperative nausea and vomiting (PONV) were
      evaluated. RESULTS: Median time-to-discharge readiness was similar: F group, 4
      days (range, 2-16 days); Fs group, 4 days (range, 2-7 days); and FCS group, 4
      days (range, 2-9 days; P = 0.631). No significant differences were found
      regarding knee function, local anesthetic consumption, or postoperative nausea
      and vomiting. During the day of surgery, pain was moderate to severe in the F
      group, whereas Fs and FCS groups experienced minimal pain (P < 0.01). Patients in
      the F group required significantly more supplemental morphine on the day of
      surgery and the first postoperative day. Until the second postoperative day, pain
      was significantly less in the FCS group (P < 0.01). CONCLUSIONS: A single
      injection or continuous sciatic nerve block in addition to a femoral nerve block
      did not influence time-to-discharge readiness. A single-injection sciatic nerve
      block can reduce severe pain on the day of the surgery, whereas a continuous
      sciatic nerve block reduces moderate pain during mobilization on the first 2
      postoperative days.

PMID- 21857274
TI  - High-resolution ultrasound accurately identifies the medial antebrachial
      cutaneous nerve at the midarm level: a clinical anatomic study.
AB  - OBJECTIVES: The present prospective volunteer study was designed to describe a
      technique for ultrasound identification of the medial antebrachial cutaneous
      nerve (MACN) and a technique for ultrasound-guided blockade of this sensory nerve
      of the upper limb. METHODS: Twenty male volunteers were included in this study.
      After cross-sectional ultrasound identification of the MACN at the upper arm,
      where it is closely adjacent to the basilic vein, a selective blockade via an in
      plane needle guidance technique was performed with 0.3 mL of mepivacaine 1.5%
      under direct ultrasound visualization. Sensory loss to pinprick at the upper
      extremity was evaluated and compared with the contralateral side. RESULTS:
      Constant ultrasound visualization of the MACN adjacent to the basilic vein at the
      upper arm level was possible in all cases. Blockade of the MACN under direct
      visualization was associated with a 100% success rate. CONCLUSIONS: The results
      of this investigation enable selective blockade of the MACN via ultrasound.
      Moreover, our data provide insight regarding the specific anatomic course and the
      integrity of this sensory nerve, which could be used for plastic and
      reconstructive surgical indications and for diagnosis of nerve injury.

PMID- 21857275
TI  - Minimum effective volume of lidocaine for ultrasound-guided supraclavicular
      block.
AB  - BACKGROUND: The aim of this study was to determine the minimum effective volume
      of lidocaine 1.5% with epinephrine 5 MUg/mL in 90% of patients (MEV90) for double
      injection ultrasound-guided supraclavicular block (SCB). METHODS: Using an in
      plane technique and a lateral to medial direction, a double-injection ultrasound
      guided SCB was performed. A 17-gauge, 8-cm Tuohy needle was initially advanced
      until its tip was positioned at the intersection of the first rib and subclavian
      artery ("corner pocket"). Half the volume of lidocaine was injected in this
      location. Subsequently, the needle was redirected toward the neural cluster
      formed by the trunks and divisions of the brachial plexus. The remaining volume
      of lidocaine was deposited in this location. Volume assignment was carried out
      using a biased coin design up-and-down sequential method, where the total volume
      of local anesthetic administered to each patient depended on the response of the
      previous one. In case of failure, the next subject received a higher volume
      (defined as the previous volume with an increment of 2.5 mL). If the previous
      patient had a successful block, the next subject was randomized to a lower volume
      (defined as the previous volume with a decrement of 2.5 mL), with a probability
      of b = 0.11, or the same volume, with a probability of 1 - b = 0.89. Each
      increment or decrement was evenly distributed between the "corner pocket" (1.25
      mL) and neural cluster (1.25 mL). Lidocaine 1.5% with epinephrine 5 MUg/mL was
      used in all subjects. Success was defined, at 30 minutes, as a minimal score of
      14 of 16 points using a composite scale encompassing sensory and motor block.
      Patients undergoing surgery of the elbow, forearm, wrist, or hand were
      prospectively enrolled until 45 successful blocks were obtained. RESULTS: Fifty
      four patients were included in the study. Using isotonic regression and bootstrap
      confidence interval, the MEV90 for double-injection ultrasound-guided SCB was
      estimated to be 32 mL (95% confidence interval, 30-34 mL). All patients with a
      minimal composite score of 14 points at 30 minutes achieved surgical anesthesia
      intraoperatively. CONCLUSIONS: For double-injection ultrasound-guided SCB, the
      MEV90 of lidocaine 1.5% with epinephrine 5 MUg/mL is 32 mL. Further dose finding
      studies are required for other concentrations of lidocaine, other local
      anesthetic agents and single-injection techniques.

PMID- 21857276
TI  - Does continuous sciatic nerve block improve postoperative analgesia and early
      rehabilitation after total knee arthroplasty? A prospective, randomized, double
      blinded study.
AB  - INTRODUCTION: The aim of this prospective, randomized, double-blind study was to
      evaluate whether continuous sciatic nerve block can improve postoperative pain
      relief and early rehabilitation compared with single-injection sciatic nerve
      block in patients undergoing total knee arthroplasty (TKA) and lumbar plexus
      block. METHODS: After ethical committee approval and written informed consent, 38
      patients with ASA physical status I to II were enrolled. The first group received
      continuous sciatic and continuous lumbar plexus blocks (group regional or R, n =
      19), whereas the second group received a single sciatic nerve block followed by
      saline infusion through the sciatic catheter and continuous lumbar plexus block
      (group control or C, n = 19). We assessed morphine consumption, scores for visual
      analog scale for pain at rest (VASr), and during continuous passive motion (VASi
      during CPM) for 48 hours postoperatively. Effectiveness of early ambulation was
      also evaluated. RESULTS: Scores for VASr and VASi during CPM, as well as morphine
      consumption, were significantly higher in group C than in group R (P < 0.01).
      Moreover, patients in group R showed earlier rehabilitation with more effective
      ambulation (P < 0.05). CONCLUSIONS: Continuous sciatic nerve block improves
      analgesia, decreases morphine request, and improves early rehabilitation compared
      with single-injection sciatic nerve block in patients undergoing TKA and lumbar
      plexus block.

PMID- 21857277
TI  - The influence of adjuvants used in regional anesthesia on lidocaine-induced
      neurotoxicity in vitro.
AB  - BACKGROUND: Neurotoxic properties of local anesthetics can rarely lead to
      irreversible neuronal damage as in cauda equina syndrome. Clinically, local
      anesthetics are often combined with adjuvants to improve or prolong the
      anesthetic effect, whereas the impact of such adjuvants on lidocaine-induced
      apoptosis is unclear. Therefore, we investigated the influence of different
      adjuvants on the neurotoxicity of lidocaine. METHODS: Human neuroblastoma cells
      and primary rat astrocytes were incubated for 24 hrs with lidocaine at a toxic
      concentration alone and in combination with morphine, sufentanil, clonidine,
      epinephrine, neostigmine, ketamine, and midazolam. Subsequently, the rates of
      cell death and early apoptosis were measured by flow cytometry in neuroblastoma
      cells, whereas astrocyte viability was analyzed by mitochondrial activity assay.
      In addition, isobolograms were calculated to describe the additive effects of
      lidocaine with ketamine or midazolam, respectively. RESULTS: Coadministration of
      lidocaine with sufentanil, clonidine, epinephrine, and neostigmine did not alter
      the rates of cell death compared with cells treated with lidocaine alone.
      Morphine improved the viability of astrocytes only at concentrations beyond those
      occurring clinically. In contrast, coincubation of lidocaine with ketamine or
      midazolam led to significantly increased rates of cell death. The combined
      toxicity of ketamine and lidocaine was additive, whereas the combined toxicity of
      midazolam and lidocaine was subadditive. CONCLUSIONS: Sufentanil, clonidine,
      epinephrine, and neostigmine do not influence the neurotoxicity of lidocaine in
      vitro. Morphine may have some cytoprotective effect at concentrations greater
      than those seen intrathecally in humans. In contrast, ketamine and midazolam
      increase the neurotoxicity of lidocaine in vitro, presumably by additive
      induction of mitochondrial apoptosis.

PMID- 21857278
TI  - Monitoring nonadherence and acute rejection with variation in blood
      immunosuppressant levels in pediatric renal transplantation.
AB  - BACKGROUND: Acute rejection associated with medication nonadherence is a major
      cause of allograft loss in pediatric kidney transplant patients. There is
      currently no reliable method to detect medication nonadherence and prevent
      allograft rejection. METHODS: In 46 pediatric patients who underwent renal
      transplantation between 2002 and 2003, the variation of serum drug levels was
      studied as a potential objective tool to monitor medication nonadherence.
      Tacrolimus (TAC) and mycophenolic acid (MPA) trough levels were measured from 1
      to 12 months posttransplant, and standard deviation (SD) and percent coefficient
      of variation (CV%) were calculated. Because SD increased as mean trough levels
      rose, CV% (CV%=SD/mean multiplied by 100%) was used to eliminate this confounding
      effect. RESULTS: Ten of 46 patients had biopsy-proven rejection. The median TAC
      CV% was 53.4% in patients with biopsy-proven rejection, which was significantly
      higher than 30% in those without rejection (P=0.005). Median MPA CV% was 51.9% in
      patients without rejection and 45.1% in patients with rejection (P=NS). High TAC
      CV% correlated with increased risk for rejection, whereas MPA CV% did not.
      CONCLUSION: The TAC CV% seems to be a useful and superior marker, compared with
      SD alone, for assessing medication nonadherence and the possibility of allograft
      rejection in pediatric renal transplantation.

PMID- 21857279
TI  - Implementation and operational research in francophone Africa. Introduction.

PMID- 21857280
TI  - Attitudes and practices of health care workers toward routine HIV testing of
      infants in Cote d'Ivoire: the PEDI-TEST ANRS 12165 Project.
AB  - OBJECTIVE: We assessed attitudes and practices of health care workers (HCWs)
      toward HIV counselling and testing (CT) routinely offered to infants in health
      facilities in Abidjan, Cote d'Ivoire. METHODS: We performed a cross-sectional
      survey inquiring on systematic HIV CT offered to children aged 6-26 weeks
      attending postnatal care for either immunization or pediatric care and to their
      parents in 4 community health centres rolling-out access to antiretroviral
      therapy. Data were collected using standardized anonymous self-questionnaires
      directed to all HCWs involved. RESULTS: One-hundred five HCWs were interviewed in
      2008: 30% were social workers, 27% physicians, 24% nurses and 19% laboratory
      technicians. Among immunization staff (n = 45), none trained in child CT versus
      26% in pediatric services (n = 60, P < 0001). Almost all staff believed that it
      is important to offer HIV screening services to children and the best place could
      be during pediatric consultations. In their daily work, 22% of immunization staff
      and 48% of pediatric care staff had already been dealing with early HIV CT (P =
      0.01). Facing a child suspected to be HIV infected, only 54% of providers in
      pediatrics and 71% in immunization would offer CT to all family members (P =
      0.01). CONCLUSIONS: In Abidjan, although HCWs were generally in favour of
      pediatric HIV screening, very few had received specific training to do so.
      Deleguation of CT to the primary care level could improve coverage of CT
      services. It is urgent to train HCWs to promote early infant HIV diagnosis to
      improve earlier access to antiretroviral therapy in West African HIV-infected
      children.

PMID- 21857281
TI  - Individual and structural factors associated with HIV status disclosure to main
      partner in Cameroon: ANRS 12-116 EVAL survey, 2006-2007.
AB  - Encouraging HIV-positive people to disclose their serostatus to their main
      partner is considered as a key component of secondary prevention. The purpose of
      this study was to identify individual and structural factors associated with HIV
      serostatus disclosure to one's steady partner in Cameroon, a country which has
      implemented a large program for access to antiretroviral therapy. We used data
      from the cross-sectional, nationally representative survey, ANRS 12-116 EVAL
      (Evaluation du programme camerounais d'acces aux traitements antiretroviraux-
      Impact sur la prise en charge et les conditions de vie de la population infectee
      par le VIH), conducted between 2006 and 2007 among HIV-infected outpatients
      attending health care facilities. Among the 1673 HIV-positive individuals
      reporting a steady partner at the time of the survey (61% women), 85.4% (n =
      1429) had disclosed their serostatus to them; 77% of the respondents were
      receiving antiretroviral therapy. Multivariate analysis based on multilevel
      modeling approaches showed that the following individual factors were associated
      with disclosure: living with one's steady partner, living with children,
      reporting systematic condom use or sexual abstinence with one's steady partner,
      being a woman who is not the head of the household, and finally having HIV
      infected people among friends or relatives and not living below the poverty line.
      Structural factors associated with disclosure were as follows: attending national
      health facilities in the country's capital cities Yaounde or Douala and having
      access to psychosocial or economical support interventions. These results
      strengthen the argument for the introduction or development of psychosocial
      interventions at all levels of organization in Cameroonian hospitals as an
      important component of public health policies for those living with HIV.

PMID- 21857282
TI  - Resistance to antiretroviral drugs in treated and drug-naive patients in the
      Democratic Republic of Congo.
AB  - BACKGROUND: We studied virological outcome and drug resistance in patients on
      antiretroviral therapy (ART) in health care centers in the Democratic Republic of
      Congo and looked for the presence of drug resistance in antiretroviral-naive
      patients attending the same clinics. METHODS: In 2008, we conducted a cross
      sectional survey among patients on ART for >= 12 months in 4 major cities
      [Kinshasa (n = 289), Matadi (n = 198), Lubumbashi (n = 77), and Mbuji-Mayi (n =
      103)]. Genotypic drug resistance tests were done with an in-house assay on
      samples with viral load >1000 copies/mL. ART-naive patients (n = 283) were also
      consecutively enrolled in the same clinics. RESULTS: Of the 667 patients on ART,
      >98% received Lamivudine + Stavudine/azidothymidine + Nevirapine/Efavirenz as
      first-line regimen and 74.4% were women. Median time on ART was 25 months
      [interquartile ratio (IQR), 19-32] in Kinshasa, 26 months (IQR, 19-32) in Matadi,
      27 months (IQR, 19-44) in Lubumbashi, and 19 months (IQR, 16-24) in Mbuji-Mayi. A
      total of 97 patients (14.6%) had viral load >1000 copies/mL, and among the 93
      successfully sequenced samples, 78 (83.9%) were resistant to at least 1 drug of
      their ART regimen: 68 harbored resistance mutations to nucleoside reverse
      transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor
      (NNRTI), 2 to NRTI only, 7 to NNRTI only, and 1 to NRTI + NNRTI + protease
      inhibitor. The majority of patients, 70/78 (89.7%), were resistant to at least 2
      of the 3 drugs from their treatment. The use of next-generation NNRTI, etravirine
      was already compromised for 19.2% (15/78) of the patients and 7 patients had the
      K65R mutation compromising the use of tenofovir in second-line regimens. The
      proportion of antiretroviral-resistant patients increased over time from 8.4% to
      18.6% for patients on ART for 12-23 months or >35 months (P = 0.013),
      respectively. Virological failure and rates of drug resistance were significantly
      higher among men than women, 19.9% versus 8.8%, respectively (P = 0.0001). Among
      the 253 recently diagnosed patients, 20 (7.9%) harbored resistance mutations.
      CONCLUSIONS: The accumulation of drug resistance mutations with time on ART needs
      further attention, and surveillance should be reinforced in ART programs in sub
      Saharan Africa.

PMID- 21857283
TI  - Nevirapine for the prevention of mother-to-child transmission of HIV: a nation
      wide coverage survey in Cote d'Ivoire.
AB  - BACKGROUND: Single-dose nevirapine (NVP) is the simplest antiretroviral regimen
      for the prevention of mother-to-child HIV transmission (PMTCT) in resource
      limited settings. We evaluated NVP coverage among HIV-infected delivering women
      in Cote d'Ivoire. METHODS: A cross-sectional survey of mother-infant pairs was
      conducted between November 2007 and September 2008 in 10 randomly selected
      facilities providing delivery services in the country. All sites used at least
      NVP for PMTCT. Anonymous HIV test and blood collection for NVP concentration
      measurement were performed in labor wards. NVP coverage was defined as the
      proportion of maternal and infant NVP intake confirmed by cord blood
      chromatography and direct observation. RESULTS: A total of 9953 deliveries were
      enrolled. Median maternal age was 25 years, and the median number of antenatal
      care (ANC) visits was 3. Of the 9747 women (97.9%) who made at least 1 ANC visit,
      5880 (60.3%) received an HIV test proposal, 5135 (87.3%) accepted it, and 251
      (4.9%) were diagnosed HIV infected; 176 of them (70.1%) received antiretroviral
      prophylaxis according to the medical record. Using anonymous cord blood
      surveillance, HIV prevalence was 5.9% (570 of 9646), maternal NVP coverage was
      24.3% (138 of 570), and maternal and infant NVP coverage was 17.9% (102 of 570).
      In multivariate analysis, maternal NVP coverage was associated with 2-3 ANC
      visits [adjusted odds ratio (aOR): 2.61; 95% confidence interval (CI): 1.27 to
      5.39] or >= 4 ANC visits (aOR: 3.84; 95% CI: 1.86 to 7.90) (ref. <= 1), and
      giving birth in clinic of first ANC visit (aOR: 2.21; 95% CI: 1.43 to 3.40).
      CONCLUSIONS: Maternal and infant NVP coverage was low irrespective of the method.
      Anonymous cord blood surveillance is more reliable for documenting PMTCT
      coverage.

PMID- 21857284
TI  - Medication possession ratio: predicting and decreasing loss to follow-up in
      antiretroviral treatment programs in Cote d'Ivoire.
AB  - BACKGROUND: In antiretroviral therapy (ART) programs, decreasing loss to follow
      up (LTFU) is a major priority. METHODS: We conducted a prospective study in
      Abidjan. Adults who started ART between June 2005 and May 2008 and were still in
      care 6 months later had monthly visits, biannual CD4 counts, computerized data
      collection and home visits (routine follow-up). A subset of patients also had
      biannual plasma HIV-1 RNA measurements, with a physician and a research assistant
      hired to pay particular attention to their visits (enhanced follow-up). We
      analyzed the association between 18-month outcomes and pre-ART characteristics,
      medication possession ratio (MPR) and type of follow-up. Patients were LTFU if
      their last visit was before month-18 and they had not returned to care by month
      24. RESULTS: 2,074 patients started ART, of whom 1,636 (79%) were still in care
      at month-6. The routine (n = 999) and enhanced (n = 637) groups had similar
      baseline characteristics. From month-6 to month-18, they had similar death rates
      (routine 3.6%, enhanced 3.9%, P = 0.74), but the enhanced group had significantly
      less LTFU (routine 11.3%, enhanced 5.8%, P < 0.001). In multivariate analysis,
      the risk of LTFU from month-6 to month-18 was 46% lower with enhanced follow-up,
      56% higher in patients living outside the centre area, and 4.0 fold higher in
      patients with a low MPR (<80%) between ART initiation and month-6. CONCLUSIONS:
      In patients still in care at 6 months, a low MPR in the first 6 months was
      strongly associated with further LTFU. Simple follow-up enhancement halved the
      LTFU rate in the following year.

PMID- 21857286
TI  - Short-term virological efficacy, immune reconstitution, tolerance, and adherence
      of once-daily dosing of didanosine, lamivudine, and efavirenz in HIV-1-infected
      African children: ANRS 12103 Burkiname.
AB  - Access to antiretroviral therapy (ART) and routine laboratory monitoring are
      limited for HIV-1-infected children from sub-Saharan Africa. This trial conducted
      in Bobo-Dioulasso, Burkina Faso, aimed to describe the biological efficacy,
      tolerance, and adherence of the combination of didanosine, lamivudine, efavirenz
      in once-daily administration among eligible HIV-1-infected children. From
      February 2006 to November 2007, 51 HIV-1-infected children aged from 30 months to
      15 years and eligible for ART were enrolled in a phase II open clinical trial
      with follow-up visits every 3 months. HIV-1 genotype testing was performed in
      children with plasma viral load (PVL) >1000 copies per milliliter after ART
      initiation. Children were followed for a median of 13.4 months [interquartile
      range (IQR) 12.8-14.2]. At enrollment, median CD4 count was 8% (IQR = 4.5-12).
      PVL was 341,032 (IQR = 127,838-761,539) copies per milliliter. At 12 months,
      median CD4 increased significantly by +15% (P < 10(-3)), and median PVL decreases
      significantly by -290,500 copies per milliliter (P < 10(-4)). Hemoglobin and
      platelets counts increased significantly by +1.05 g/dL (P < 10(-5)) and 108,500
      cells per milliliter (P < 10(-3)), respectively. Based on pill count, mean yearly
      adherence was 97.3%, and 48% of the children had an adherence rate >= 95% at the
      four quarterly visits. Adherence was better for girls than for boys independently
      of other sociodemographic variables or markers of HIV disease progression. Drug
      resistant mutations were found in 11 children (21.6%). This once-daily drug
      combination is associated with excellent virological efficacy, immune
      reconstitution, and good adherence. However, the high prevalence of drug
      resistance mutations is a matter of concern.

PMID- 21857288
TI  - Access to second-line antiretroviral therapeutic regimens in low-resource
      settings: experiences from Cameroon.
AB  - Cameroon is one of the few sub-Saharan countries engaged in the implementation of
      a universal public health policy on HIV/AIDS. In May 2007, second-line
      antiretroviral regimens were made available in the country; thanks to the joint
      participation of the Cameroonian government and the UNITAID/Clinton Foundation
      HIV/AIDS Initiative. This cooperation was achieved by means of a Memorandum of
      Understanding. The agreement aimed at providing free-of-charge access of 8
      antiretroviral formulations. Nevertheless, only 1.9% of the estimated 16%
      patients that are presently in need of second-line regimens has access to these
      medicines. The main hindrances to achieving scaled-up access refer to the new
      institutional arrangements that are necessary for the demand and distribution of
      these medicines, the limiting conditions for the therapeutic monitoring of second
      line treatments, at the national level and the governance of the Memorandum of
      Understanding itself.

PMID- 21857285
TI  - Adherence to antiretroviral treatment in HIV-positive patients in the Cameroon
      context: promoting the use of medication reminder methods.
AB  - OBJECTIVES: Antiretroviral treatment (ART) scale-up in sub-Saharan Africa has
      made it possible to investigate the maintenance of adherence to HIV medications.
      We describe here adherence to ART and identify its correlates in the Cameroonian
      context. DESIGN: Prospective cohort study in 9 rural district hospitals. METHODS:
      A mixed logistic regression model was used to identify factors associated with
      adherence to ART in 401 patients with data prospectively collected on adherence.
      RESULTS: Although 73% of patients were adherent after the first month on ART,
      this proportion decreased to 61% after 24 months. After adjustment for known
      factors of adherence to ART (such as knowledge, motivation and side-effects),
      patients who reported willingness to start ART before initiation, those who were
      satisfied with information provided by their physicians, and those who
      implemented reminder methods for ART intake {eg, using an alarm clock, mobile
      phone, or watch [odds ratio (95% confidence interval)] = 2.45 (1.58 to 3.79), but
      also the help of a relative to remind them or other methods} were more likely to
      be adherent to ART. CONCLUSIONS: Besides highlighting some correlates already
      known to have an impact on adherence to ART, our findings also underline the need
      to reinforce the counseling component of follow-up through innovative methods.
      Accordingly, training and implementation research should encourage the use of
      medication reminder methods, such as mobile phones, to assure adherence over time
      and improve long-term response to ART.

PMID- 21857287
TI  - Linking HIV prevention and care for community interventions among high-risk women
      in Burkina Faso--the ARNS 1222 "Yerelon" cohort.
AB  - BACKGROUND: Interventions targeting core groups such as high-risk women in Africa
      have focused mostly on HIV prevention. In this marginalized group, the delegation
      of HIV care to public services may jeopardize the effectiveness of prevention
      activities. We assessed the effect of an intervention combining prevention and
      care among high-risk women on HIV exposure and treatment outcomes. METHODS: In
      Burkina Faso, high-risk women were recruited by peer educators in an open-cohort
      study with 4-monthly follow-up visits. Primary prevention included peer-led
      information, education and communication sessions, condom distribution, regular
      HIV counselling and testing, and sexually transmitted infections management.
      Participants were offered free medical care including antiretroviral therapy
      (ART) and treatment adherence support by psychologists. RESULTS: From December
      2003, 658 high-risk women were enrolled and followed up for a median 20.8 months.
      Seven of the 489 HIV-uninfected women seroconverted (HIV incidence 0.9 of 100
      person-years, 95% confidence interval: 0.24 to 1.58). HIV incidence tended to be
      higher during the first 8 months of follow-up than thereafter (1.43 vs. 0.39 per
      100 person-years). Among 47 of 169 HIV-seropositive women who started ART, 79.4%
      achieved undetectable plasma viral load 6 months after initiation and 81.8% at 36
      months. Condom use at last sexual intercourse with clients increased from 81.7%
      at enrollment to 98.2% at 12 months (P < 0.001) and from 67.2% to 95.9% (P <
      0.001) with regular clients. CONCLUSIONS: The integration of HIV care services,
      including the provision and support of ART, with a peer-led primary prevention
      package is pivotal to reduce HIV incidence and is likely to modify the local HIV
      dynamics.

PMID- 21857289
TI  - Factors associated with history of HIV testing among pregnant women and their
      partners in Cameroon: baseline data from a Behavioral Intervention Trial (ANRS
      12127 Prenahtest).
AB  - BACKGROUND: We investigated HIV testing practices at baseline among pregnant
      women and their partners within a multicountry randomized trial aiming to
      evaluate the effect of enhanced prenatal posttest HIV counseling on men's
      involvement. METHODS: In Yaounde, Cameroon, 484 pregnant women with stable
      partners were recruited on their first antenatal care visit. We analyzed the
      coverage of previous HIV testing among women and their partners and looked for
      the factors associated with previous HIV testing, using multivariable logistic
      regression. RESULTS: Among 476 pregnant women who completed the baseline
      questionnaire, 408 (85.7%) reported having been tested for HIV already once in
      their life, 48.3% of them during a previous pregnancy. Women previously tested
      for HIV were more likely to be in a stable relationship for >5 years than those
      never tested (P < 0.001). In multivariable analysis, tested women were more
      likely to be aged between 25 and 30 years compared with women <20 years [odds
      ratio (OR) 5.5, 95% confidence interval (CI): 1.4 to 22.1], to be able to say
      whether they felt at risk for HIV infection (OR 2.1, CI: 1.1 to 3.9), and to have
      ever discussed about HIV with their partner (OR 2.7, CI: 1.1 to 6.4). Most women
      (85.1%) reported that their partner had already been tested for HIV. Reasons for
      partner HIV testing were related to self-motivation (30.0%) and clinical symptoms
      (12.7%). CONCLUSIONS: Strategies aiming at improving knowledge and couple
      communication about HIV risks need to be considered to address the remaining
      barriers to HIV testing and contribute to a couple approach to HIV prevention.

PMID- 21857291
TI  - Expanding the generation and use of economic and financial data to improve HIV
      program planning and efficiency: a global perspective.
AB  - Cost information is needed at multiple levels of health care systems to inform
      the public health response to HIV. To date, most attention has been paid to
      identifying the cost drivers of providing antiretroviral treatment, and these
      data have driven interventions that have been successful in reducing drug and
      human resource costs. The need for further cost information, especially for less
      well-studied areas such as HIV prevention, is particularly acute given global
      budget constraints and ongoing efforts to extract the greatest possible value
      from money spent on the response. Cost information can be collected from multiple
      perspectives and levels of the health care system (site, program, and national
      levels), and it is critical to choose the appropriate methodology in order to
      generate the appropriate information for decision-making. Organizations such as
      United States President's Emergency Plan for AIDS Relief, the Global Fund to
      Fight AIDS, Tuberculosis, and Malaria, and other organizations are working
      together to bridge the divide between the fields of economics and HIV program
      implementation by accelerating the collection of cost data and building further
      local demand and capacity for their use.

PMID- 21857290
TI  - Optimizing antiretroviral product selection: a sample approach to improving
      patient outcomes, saving money, and scaling-up health services in developing
      countries.
AB  - Over the last decade, increased funding to support HIV treatment programs has
      enabled millions of new patients in developing countries to access the
      medications they need. Today, although demand for antiretrovirals continues to
      grow, the financial crisis has severely constrained funding leaving countries
      with difficult choices on program prioritization. Product optimization is one
      solution countries can pursue to continue to improve patient care while also
      uncovering savings that can be used for further scale up or other health system
      needs. Program managers can make procurement decisions that actually reduce
      program costs by considering additional factors beyond World Health Organization
      guidelines when making procurement decisions. These include in-country product
      availability, convenience, price, and logistics such as supply chain implications
      and laboratory testing requirements. Three immediate product selection
      opportunities in the HIV space include using boosted atazanavir in place of
      lopinovir for second-line therapy, lamivudine instead of emtricitabine in both
      first-line and second-line therapy, and tenofovir + lamivudine over abacavir +
      didanosine in second-line therapy. If these 3 opportunities were broadly
      implemented in sub-Saharan Africa and India today, approximately $300 million of
      savings would be realized over the next 5 years, enabling hundreds of thousands
      of additional patients to be treated. Although the discussion herein is specific
      to antriretrovirals, the principles of product selection are generalizable to
      diseases with multiple treatment options and fungible commodity procurement.
      Identifying and implementing approaches to overcome health system inefficiencies
      will help sustain and may expand quality care in resource-limited settings.

PMID- 21857292
TI  - Tackling health workforce shortages during antiretroviral treatment scale-up-
      experiences from Ethiopia and Malawi.
AB  - In many sub-Saharan countries, the health workforce shortage has been a major
      constraint in the scale-up of antiretroviral treatment. This human resource
      crisis has led to profound adjustments of the antiretroviral treatment care
      delivery model in several countries in the region. It also inspired some
      governments to take swift measures to substantially increase human resources
      capacity. This article draws on the experience of Malawi and Ethiopia, which have
      been able to successfully increase their health workforce over a relatively short
      period, allowing scaling up of antiretroviral treatment. Additional international
      HIV funding and strong political commitment made possible this exceptional
      response. Both countries implemented a combination of measures to tackle the
      human resource crisis: the delegation of medical and administrative tasks to
      lower health cadres and lay workers, the introduction of new health cadres, the
      reinforcement of pre-service training, and improving health staff remuneration.
      In particular, the involvement of community and lay health workers in HIV-related
      service delivery substantially increased the health workforce. The involvement of
      lay cadres has important long-term implications. To sustain results, continued
      political commitment, ongoing training and supervision to maintain quality of
      care, and strategies to avoid attrition among lay cadres will be essential.
      Although task shifting and involvement of lay cadres allowed bridging of the
      human resource gap in a short time, other strategies have to be considered
      simultaneously, and all interventions must be maintained over a longer period to
      yield results.

PMID- 21857293
TI  - Moving forward on human resources for health: next steps for scaling up toward
      universal access to HIV/AIDS prevention, treatment, and care.
AB  - In 2008, the Global Health Workforce Alliance commissioned a technical working
      group to examine the human resources for health implications of scaling up to
      reach the Millennium Development Goal 6 of universal access to HIV/AIDS
      prevention, treatment, care, and support by 2010. The analysis and interventions
      recommended in the working group report, which was launched at the Second Global
      Forum on Human Resources for Health in Bangkok, Thailand, in January 2011, are
      based on two research methods: literature reviews covering the period from 2000
      to 2008 and a rapid situational analysis produced by teams working in 5 countries
      (Cote d'Ivoire, Ethiopia, Mozambique, Thailand, and Zambia). The authors' intent
      in this article is to assist the Alliance in maintaining the momentum of the
      forum and the enthusiasm generated by the working group's report to make a
      difference at the country level by moving from recommendation to action.

PMID- 21857294
TI  - Leveraging the private health sector to enhance HIV service delivery in lower
      income countries.
AB  - Evidence that the private health sector is a key player in delivering health
      services and impacting health outcomes, including those related to HIV/AIDS,
      underscores the need to optimize the role of the private health sector to scale
      up national HIV responses in lower-income countries. This article reviews
      findings on the types of HIV/AIDS services provided by the private health sector
      in developing countries and elaborates on the role of private providers of HIV
      services in Ethiopia. Drawing on data from the nation's innovative Private Health
      Sector Project, a pilot project that has demonstrated the feasibility of public
      private partnerships in this area, the article highlights the potential for
      national governments to scale up HIV/AIDS services by leveraging private health
      sector resources, innovations, and expertise while working to regulate quality
      and cost of services. Although concerns about uneven quality and affordability of
      private sector health services must be addressed through regulation, policy, or
      other innovative approaches, we argue that the benefits of leveraging the private
      sector outweigh these challenges, particularly in light of finite donor and
      public domestic resources.

PMID- 21857295
TI  - HIV and health systems: research to bridge the divide.
AB  - Concern that HIV programs in low-income countries may strain weak health systems
      and undermine achievement of other priority health goals has resulted in a
      research agenda focused on measuring the effects of past HIV investments on non
      HIV services and outcomes. However, this research has limited value for informing
      future health policies and programs, which increasingly view health systems as
      the common platform for delivery of HIV and other health services. These policies
      reflect a shift in the framing of HIV care and treatment from emergency response
      to routine health service. In this paradigm, relevant areas for research are
      strengthening, scaling, and sustaining health systems in low-income countries to
      reduce all-cause mortality and morbidity, including deaths from HIV. To build an
      evidence base to support current and future health systems and policy,
      researchers need to move from retrospective studies to prospective research and
      adopt innovative study designs and analytic methods.

PMID- 21857296
TI  - Bridging the divide.

PMID- 21857297
TI  - Game changers: why did the scale-up of HIV treatment work despite weak health
      systems?
AB  - Game changers are radical innovations that result in fundamental and durable
      changes. The global HIV program scale-up witnessed over the past decade has
      included some innovations that are not well appreciated. The willingness to
      rapidly adopt and implement innovations, the flexibility and speed of program
      implementation, and the readiness to re-examine professional roles are just a few
      of such game changers. However, moving ahead, further work is needed to enhance
      the quality of programs, to energetically tackle HIV prevention, to build on this
      success, and to address other health threats that these same communities face.

PMID- 21857298
TI  - Why did the scale-up of HIV treatment work? A case example from Malawi.
AB  - The national scale-up of antiretroviral therapy (ART) in Malawi is based on a
      public health approach, with principles and practices borrowed from the
      successful DOTS (directly observed treatment short course-the system used to
      successfully deliver antituberculosis treatment to people in some of the poorest
      countries of the world) tuberculosis control framework. During the first 6 years,
      the number of patients registered on treatment increased from 3000 to >350,000 in
      both the public and private sectors. The most important reasons for this success
      have been strong international and national leadership combined with adequate
      funds, a standardized approach to ART with practical guidelines, an approved
      national scale-up plan with clear, time-bound milestones; investment in an
      intensive program of training and accreditation of ART sites, quarterly
      supervision and monitoring of ART and operational research, rational drug
      forecasting and no stock-outs of drugs during the first few years, and
      involvement of the private sector. The looming challenges of human resources,
      guaranteed financial support, better but also more expensive ART regimens, use of
      electronic medical records to monitor response to therapy, and attention to HIV
      prevention need to be met head-on and solved if the momentum of the earlier years
      is to be maintained.

PMID- 21857299
TI  - No need for apologies.
AB  - The expansion of access to antiretroviral therapy for millions of persons living
      with HIV in low-income countries has been lauded by many. However, the investment
      in such programs has at the same time been criticized by others, who claim
      diversion of resources from HIV prevention efforts and from other important
      health threats in these same countries. Yet, the time is right to recommit to the
      goal of universal access to HIV prevention and treatment while garnering the
      lessons learned from HIV programming and building on the platform it has
      established in confronting other health threats.

PMID- 21857300
TI  - Critical interactions between the Global Fund-supported HIV programs and the
      health system in Ghana.
AB  - The support of global health initiatives in recipient countries has been
      vigorously debated. Critics are concerned that disease-specific programs may be
      creating vertical and parallel service delivery structures that to some extent
      undermine health systems. This case study of Ghana aimed to explore how the
      Global Fund-supported HIV program interacts with the health system there and to
      map the extent and nature of integration of the national disease program across 6
      key health systems functions. Qualitative interviews of national stakeholders
      were conducted to understand the perceptions of the strengths and weaknesses of
      the relationship between Global Fund-supported activities and the health system
      and to identify positive synergies and unintended consequences of integration.
      Ghana has a well-functioning sector-wide approach to financing its health system,
      with a strong emphasis on integrated care delivery. Ghana has benefited from US
      $175 million of approved Global Fund support to address the HIV epidemic,
      accounting for almost 85% of the National AIDS Control Program budget.
      Investments in infrastructure, human resources, and commodities have enabled HIV
      interventions to increase exponentially. Global Fund-supported activities have
      been well integrated into key health system functions to strengthen them,
      especially financing, planning, service delivery, and demand generation. Yet,
      with governance and monitoring and evaluation functions, parallel structures to
      national systems have emerged, leading to inefficiencies. This case study
      demonstrates that interactions and integration are highly varied across different
      health system functions, and strong government leadership has facilitated the
      integration of Global Fund-supported activities within national programs.

PMID- 21857301
TI  - Leveraging HIV programs to deliver an integrated package of health services: some
      words of caution.
AB  - Over the past decade, HIV programs have been successfully scaled up in many
      developing countries, leading some to wonder how the investments made into HIV
      infrastructure could be leveraged to deliver additional health services. Although
      the concept is appealing from many perspectives, integrating additional health
      services into existing vertical HIV infrastructure may not mitigate some of the
      challenges these programs have introduced in implementing countries. In addition,
      this approach to integration may countervail parallel efforts of the global
      health community to strengthen health systems and improve aid effectiveness. It
      might also undermine the HIV programs themselves. International donors and health
      system planners should carefully consider whether the benefits outweigh the
      potential costs of these well-intentioned integration efforts.

PMID- 21857302
TI  - Integrating HIV and maternal health services: will organizational culture clash
      sow the seeds of a new and improved implementation practice?
AB  - Drawing on an analysis by Pritchett et al of the "techniques of persistent
      implementation failure" common across many development sectors, this commentary
      suggests that health systems attempting to integrate maternal health and HIV
      services may need to contend with a profound clash of organizational cultures.
      For decades, countries have been pressed to implement global "best practices" in
      maternal health without attention to the systemic capacity building needed to
      support complex interventions. The result is often form without function, a kind
      of "isomorphic mimicry" in which policy documents and program plans that meet
      global standards ultimately camouflage deep dysfunction in the actual delivery of
      lifesaving services. As a result, the organizational culture that surrounds
      maternal health services often stands in stark contrast to the can-do style that
      has characterized the rapid, well-resourced deployment of HIV services over the
      last few years. As integration proceeds, the resolution of this clash may hold
      the seeds of a much-needed transformation of implementation support practices in
      both fields.

PMID- 21857303
TI  - Leveraging progress in prevention of mother-to-child transmission of HIV for
      improved maternal, neonatal, and child health services.
AB  - Finding ways to leverage the substantial investment in prevention of mother-to
      child transmission of HIV to address other maternal, neonatal, and child health
      threats is a priority. With increased emphasis on health systems strengthening
      and the integration of disease-specific initiatives within primary care, we
      propose three areas for consideration: 1) increased integration of service
      delivery; 2) adaptation of successful implementation models; and 3) a
      reconceptualization of the care continuums for prevention of mother-to-child HIV
      transmission and maternal, neonatal, and child health.

PMID- 21857304
TI  - Scaling up chronic care systems: leveraging HIV programs to support
      noncommunicable disease services.
AB  - The scale-up of HIV services in lower-income countries has created the first
      large-scale continuity care program in many settings. Although HIV and chronic
      noncommunicable diseases are thought of as quite different challenges and tend to
      be "siloed" throughout the health system, the availability of treatment has
      transformed HIV into a chronic condition-and HIV programs have developed the
      systems, tools, and approaches needed to support continuity care in the local
      context. In many cases, HIV programs have developed practical and contextually
      appropriate resources that might be used to support nascent noncommunicable
      diseases programs.

PMID- 21857305
TI  - Building a durable response to HIV/AIDS: implications for health systems.
AB  - The remarkable rise in investments for HIV control programs in 2003-2010 enabled
      an unprecedented expansion of access to HIV services in low-income and middle
      income countries. By the end of 2010, more than 5.2 million people were receiving
      antiretroviral therapy (ART), which transformed HIV infection, once a death
      sentence, into a long-term illness. The rapid expansion in the number of persons
      receiving ART means that health systems must continue to provide acute life
      saving care for those with advanced HIV/AIDS although also providing chronic care
      services to expanding cohorts of more stable patients who are doing well on ART.
      This expansion also means a transition from an emergency response to the
      epidemic, characterized by a public health approach, to a more integrated and
      durable approach to HIV prevention, care, and treatment services that fosters
      individualized care for those requiring long-term antiretroviral treatment. Yet
      most low-income and middle-income countries, which have weak health systems, are
      poorly prepared to make this transition. In this article, we highlight the
      challenges health systems face in developing a sustained and durable response to
      HIV/AIDS. The article analyses the readiness of health systems to combine rapid
      expansion of ART access with long-term treatment and continuity of care for a
      growing cohort of patients. We argue that effective management of a transition
      from an emergency AIDS response to long-term programatic strategies will require
      a paradigm shift that enables leveraging investments in HIV to build sustainable
      health systems for managing large cohorts of patients receiving ART although
      meeting the immediate needs of those who remain without access to HIV treatment
      and care.

PMID- 21857306
TI  - Expanding the space: inclusion of most-at-risk populations in HIV prevention,
      treatment, and care services.
AB  - The provision of appropriate HIV prevention, treatment, and care services for
      most-at-risk populations (MARP) will challenge many health care systems. For
      people who sell sex or inject drugs and for men who have sex with men, stigma,
      discrimination, and criminalization can limit access to care, inhibit service
      uptake, and reduce the disclosure of risks. Several models for provision of HIV
      services to MARP may address these issues. We discuss integrated models, stand
      alone services, and hybrid models, which may be appropriate for some MARP in some
      settings. Both public health and human rights frameworks concur that those at
      greatest risk should have expanded access to services.

PMID- 21857307
TI  - Building AIDS research capacity in Brazil.

PMID- 21857308
TI  - Analysis of data collected by RDS among sex workers in 10 Brazilian cities, 2009:
      estimation of the prevalence of HIV, variance, and design effect.
AB  - BACKGROUND: Respondent-driven sampling (RDS) is a chain-referral method that is
      being widely used to recruit most at-risk populations. Because the method is
      respondent driven, observations are dependent. However, few publications have
      focused on methodological challenges in the analysis of data collected by RDS.
      METHODS: In this article, we propose a method for estimating the variance of the
      HIV prevalence rate, based on the Markov transition probabilities and within
      recruitment cluster variation. The method was applied to a female commercial sex
      workers study carried out in 10 Brazilian cities in 2008. Both the inverse of
      network size and the size of the city were considered in the estimation of
      overall sampling weights. The study included a behavior questionnaire and rapid
      tests for HIV and syphilis. RESULTS: About 2523 interviews were conducted
      successfully, excluding the seeds. Results show a positive homophily between
      recruits for those HIV+; HIV- recruiters selected HIV+ recruits 4% of the time;
      HIV+ recruiters selected other HIV+ recruits 19.6% of the time, about 5 times
      higher. The prevalence rate was estimated at 4.8% (95% confidence interval: 3.4
      to 6.1), and a design effect of 2.63. CONCLUSIONS: Using statistical methods for
      complex sample designs, it was possible to estimate HIV prevalence, standard
      error, and the design effect analytically. Additionally, the proposed analysis
      lends itself to logistic regression, permitting multivariate models. The
      stratification in cities has proved suitable for reducing the effect of design
      and can be adopted in other RDS studies, provided the weights of the strata are
      known.

PMID- 21857309
TI  - Putting respondent-driven sampling on the map: insights from Rio de Janeiro,
      Brazil.
AB  - BACKGROUND: Hard-to-reach populations with high background infection rates for
      HIV are particularly relevant in countries with restricted HIV epidemics, such as
      Brazil, where the very dynamics of the epidemic depends on the bridges between
      those populations and the general population. Respondent-driven sampling (RDS)
      has been one of the key strategies to assess such populations and inform policy
      making. OBJECTIVES: To geocode and visualize an RDS-based study on 605 heavy drug
      users, conducted in Rio de Janeiro, in 2009. METHODS: The location and
      characteristics of the residence of interviewees were collected by an Audio
      Computer-Assisted Self Interview (ACASI) survey, supplemented by additional
      information. Place of residence was geocoded and depicted as network graphs and
      thematic maps. RESULTS: The geographic distribution of the interviewees was found
      to be very heterogeneous. The recruiting chains progressed slowly during the
      successive waves toward neighborhoods far from the initial geographic axis.
      Despite the undeniable progress toward a broader geographic scope as the study
      proceeded through 11 successive waves, some key geographic areas were excluded.
      CONCLUSIONS: In the context of a large and complex urban area, plagued by
      structural violence and with a lively drug scene, the study made evident network
      bottlenecks. Either secondary to its relatively small sample size, structural
      constraints, or a combination of both, such bottlenecks represent a formidable
      challenge for RDS or other network-based methods as applied to urban settings
      with characteristics similar to Rio de Janeiro.

PMID- 21857310
TI  - Risk factors associated with HIV prevalence among female sex workers in 10
      Brazilian cities.
AB  - BACKGROUND: HIV prevalence is 15 times higher among female sex workers (FSWs)
      than in the overall Brazilian female population. In this article, we investigated
      factors associated to HIV infection among FSW, recruited by Respondent-driven
      sampling (RDS), in 10 Brazilian cities in 2008-2009. METHOD: The total sampling
      was 2523 FSWs. The variables considered in the study included sociodemographic
      characteristics and those related to profession, knowledge, and source of
      information on sexually transmitted infection/AIDS, access to condoms, sexual
      behavior, health care and sexually transmitted infection signs, discrimination
      and violence, and the use of alcohol and drugs. Sampling weights were
      proportional to the inverse of network size and for the generation of global
      results for the 10 cities, data were calibrated by the population size.
      Multivariate logistic regression models were used, taking into account the
      dependency structure of observations. RESULTS: The longest period of prostitution
      (odds ratio [OR], 1.040; 95% confidence interval [CI], 1.013-1.067), the lowest
      price charged for sex (OR, 0.713; 95% CI, 0.522-0.970), the association with
      other sexually transmitted infections such as syphilis (OR, 2.186; 95% CI, 1.064
      4.488), and the fact of would waive the use of condom on client's request (OR,
      3.735; 95% CI, 1.449-9.661) were the most important associated risk factors to
      HIV infection among FSWs. Purchase of condoms (OR, 0.503; 95% CI, 0.304-0.833)
      was a relevant preventive factor. CONCLUSIONS: The use of RDS proved to be
      appropriate for the recruitment of FSWs as long as the statistical analysis takes
      into account the dependency structure of observations. The HIV infection
      predictors here depicted can support public health policies focused on this
      population group in Brazil.

PMID- 21857311
TI  - Reliability of self-report of HIV status among men who have sex with men in
      Brazil.
AB  - INTRODUCTION: The aim of this study was to evaluate the reliability of self
      reported HIV among men who have sex with men (MSM) in Brazil. METHODS: MSM 18
      years of age or older were recruited to a multicenter study using respondent
      driven sampling. We compared self-report of the HIV test with a rapid HIV test
      using the kappa coefficient. RESULTS: A total of 3859 MSM were recruited, and 39%
      reported ever having an HIV test; their results were reported and they agreed to
      a new test. Agreement between self-report and the test was very good (kappa =
      0.88). CONCLUSION: Our results suggest that self-report of HIV infection is a
      reliable indicator among MSM.

PMID- 21857312
TI  - HIV testing in psychiatric patients in Brazil.
AB  - BACKGROUND: There is evidence that a high proportion of people living with HIV
      infection are unaware of their serologic status, which indicates unmet prevention
      needs. The aim of the present study was to estimate the rate of lifetime HIV
      testing and assess the association between previous HIV testing and
      sociodemographic, clinical characteristics, and risk behaviors in psychiatric
      patients. METHODS: Cross-sectional national multicenter study including 2380
      chronic mentally ill patients randomly selected from 26 Brazilian mental health
      institutions. Multivariate logistic regression analysis was used to describe the
      association between patient characteristics and previous HIV testing. RESULTS:
      The rate of previous lifetime HIV testing was 27%. Most participants were female
      (52%), 40 years old or younger (52%) with low schooling (59%), and had previous
      psychiatric hospitalizations (57%) and schizophrenia as a primary condition
      (48%). Being tested for HIV was independently associated (P < 0.05) in the
      multivariate analysis with higher schooling, being younger than 40 years old,
      living alone, having other self-reported medical conditions, higher HIV/AIDS
      knowledge, substance use as a main psychiatric condition, a history of sexually
      transmitted diseases, sexual abuse, and inconsistent lifetime condom use.
      However, those who never had sexual intercourse and did not know their HIV risk
      were less likely to be tested. CONCLUSIONS: The rate of HIV testing among these
      psychiatric patients was low despite their increased risk for HIV infection.
      These findings support the need for increasing HIV testing and awareness of HIV
      status among psychiatric patients. Mental health providers should play an active
      role in providing HIV testing and counseling to this population.

PMID- 21857313
TI  - Eliminating vertical transmission of HIV in Sao Paulo, Brazil: progress and
      challenges.
AB  - BACKGROUND: HIV infection in children is an important public health problem in
      the world, mainly in poorer countries. If all recommendations are followed, the
      elimination of HIV vertical transmission is a concrete possibility. This study
      aims to estimate vertical transmission rates of HIV in Sao Paulo State, Brazil,
      based on pregnant women diagnosed and reported in 2006, identifying potentially
      associated factors. METHODS: This study involves a retrospective cross-sectional
      analysis of information systems and records of infected pregnant women and
      children exposed to HIV. The rate of vertical transmission was estimated and
      variables associated with the antenatal, delivery, and postnatal periods were
      analyzed by the chi-square test, and Fisher exact test was used for variables
      with an expected frequency <5. The relative risks were calculated with 95%
      confidence intervals. RESULTS: The rate of vertical transmission in Sao Paulo
      state was 2.7% (95% confidence interval: 1.86 to 3.94) in 2006, decreasing 83.1%
      in comparison with 1988-1993. The main associated variables were lack of prenatal
      visits or <6 visits, no antiretroviral prophylaxis during labor or neonatal use
      for <6 weeks, and maternal breastfeeding. CONCLUSIONS: There is a decreasing
      trend of HIV vertical transmission in Sao Paulo with levels approaching
      elimination, which seems to be associated with antiretroviral policy and
      interruption of breastfeeding. Although there are serious operational issues,
      conditions exist to respond effectively. Sao Paulo state demonstrates that it is
      possible to achieve advanced levels of control for this mode of HIV transmission.

PMID- 21857314
TI  - Immune status at presentation for HIV clinical care in Rio de Janeiro and
      Baltimore.
AB  - BACKGROUND: Late presentation to HIV clinical care increases individual risk for
      (multiple) clinical events and death, and decreases successful response to highly
      active antiretroviral therapy (HAART). In Brazil, provision of HAART free of
      charge to all individuals infected with HIV could lead to increased testing and
      linkage to care. METHODS: We assessed the immune status of 2555 patients who
      newly presented for HIV clinical care between 1997 and 2009 at the Johns Hopkins
      Clinical Cohort, in Baltimore, Md, and at the Instituto de Pesquisa Clinica
      Evandro Chagas Clinical Cohort, in Rio de Janeiro, Brazil. The mean change in the
      CD4 cell count per year was estimated using multivariate linear regression
      models. RESULTS: Overall, from 1997 to 2009, 56% and 54% of the patients
      presented for HIV clinical care with CD4 count <=350 cells per cubic millimeter
      in Baltimore and Rio de Janeiro, respectively. On average, 75% of the patients
      presented with viral load >10,000 copies per millimeter. In Rio de Janeiro only,
      the overall adjusted per year increase in the mean CD4 cell count was
      statistically significant (5 cells/mm, 95% confidence interval: 1 to 10
      cells/mm). CONCLUSIONS: We found that, over years, the majority of patients
      presented late, that is, with a CD4 count <350 cells per cubic millimeter. Our
      findings indicate that, despite the availability of HAART for more than a decade,
      and mass media campaigns stimulating HIV testing in both countries, the
      proportion of patients who start therapy at an advanced stage of the disease is
      still high.

PMID- 21857315
TI  - A randomized, clinical trial to evaluate the impact of regular physical activity
      on the quality of life, body morphology and metabolic parameters of patients with
      AIDS in Salvador, Brazil.
AB  - Patients with AIDS under antiretroviral therapy often present with metabolic
      problems associated with HIV infection and its therapy, which can affect their
      quality of life. The knowledge on the potential benefits of regular physical
      exercises for HIV-infected patients is limited. OBJECTIVE: We conducted a
      clinical trial to evaluate the impact of regular physical activity on quality of
      life, anatomic disturbances, and/or metabolic changes in patients with AIDS in
      the city of Salvador, Brazil. METHODS: Patients were randomly assigned in monthly
      workshops (1-hour duration) to discuss the importance of physical activity and
      receive nutritional counseling (control group) or to receive a 1-hour supervised
      gym class three times a week plus monthly nutritional counseling (intervention
      group). Before and after intervention, body composition, maximum oxygen
      consumption, metabolic equivalent, blood count, fasting total cholesterol, high
      density lipoprotein, triglycerides, glucose, HIV viral load and CD4/CD8 counts,
      and resting heart rate were measured. Quality of life was evaluated at baseline
      and after 24 weeks. RESULTS: The domains of quality of life, general health,
      vitality and mental health increased in the exercise group (P < 0.05) compared
      with the control group. In the exercise group, fat mass (P = 0.04), the resting
      heart rate (P = 0.001), waist circumference (P = 0.002), and glucose (P = 0.003)
      decreased. Muscle mass (P = 0.002), CD4 T cells (P = 0.002), metabolic equivalent
      (P = 0.014), and maximum oxygen consumption (P = 0.05) increased. CONCLUSION: The
      practice of regular exercise, coupled with nutritional guidance, in individuals
      with HIV/AIDS significantly improves the quality of life.

PMID- 21857317
TI  - Prevalence of etravirine-associated mutations in clinical samples with genotypic
      resistance to nevirapine and efavirenz in Brazilian clinics.
AB  - Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent and well
      tolerated. In Brazil, the first-generation NNRTI efavirenz is included in the
      majority of first-line antiretroviral treatment regimens. In this study, we
      evaluated the effectiveness of etravirine, a new second-generation NNRTI, among
      patients failing antiretroviral regimens containing first-generation NNRTIs. We
      assessed single resistance mutations to etravirine as well as complex resistance
      mutations profile and discuss the potential of introducing etravirine as salvage
      therapy.

PMID- 21857316
TI  - Antiretroviral drug resistance in a respondent-driven sample of HIV-infected men
      who have sex with men in Brazil.
AB  - BACKGROUND: : There are few studies on HIV subtypes and primary and secondary
      antiretroviral drug resistance (ADR) in community-recruited samples in Brazil. We
      analyzed HIV clade diversity and prevalence of mutations associated with ADR in
      men who have sex with men in all five regions of Brazil. METHODS: : Using
      respondent-driven sampling, we recruited 3515 men who have sex with men in nine
      cities: 299 (9.5%) were HIV-positive; 143 subjects had adequate genotyping and
      epidemiologic data. Forty-four (30.8%) subjects were antiretroviral therapy
      experienced (AE) and 99 (69.2%) antiretroviral therapy-naive (AN). We sequenced
      the reverse transcriptase and protease regions of the virus and analyzed them for
      drug resistant mutations using World Health Organization guidelines. RESULTS: :
      The most common subtypes were B (81.8%), C (7.7%), and recombinant forms (6.9%).
      The overall prevalence of primary ADR resistance was 21.4% (i.e. among the AN)
      and secondary ADR was 35.8% (i.e. among the AE). The prevalence of resistance to
      protease inhibitors was 3.9% (AN) and 4.4% (AE); to nucleoside reverse
      transcriptase inhibitors 15.0% (AN) and 31.0% (AE) and to nonnucleoside reverse
      transcriptase inhibitors 5.5% (AN) and 13.2% (AE). The most common resistance
      mutation for nucleoside reverse transcriptase inhibitors was 184V (17 cases) and
      for nonnucleoside reverse transcriptase inhibitors 103N (16 cases). CONCLUSIONS:
      : Our data suggest a high level of both primary and secondary ADR in men who have
      sex with men in Brazil. Additional studies are needed to identify the correlates
      and causes of antiretroviral therapy resistance to limit the development of
      resistance among those in care and the transmission of resistant strains in the
      wider epidemic.

PMID- 21857318
TI  - Genotypic analysis of the gp41 HR1 region from HIV-1 isolates from enfuvirtide
      treated and untreated patients.
AB  - OBJECTIVE: To evaluate the polymorphisms and resistance mutations in gp41 HR1
      region of HIV-1. METHODS: The study included 28 HIV-positive patients undergoing
      enfuvirtide (ENF) treatment or not from Porto Alegre, Rio Grande do Sul state,
      and Rio de Janeiro, Rio de Janeiro state, between 2006 and 2009. Resistance
      mutations and polymorphisms of the gp41 HR1 region were detected using the
      genomic DNA of 12 ENF-untreated patients and 16 patients in ENF treatment,
      encompassing subtypes B, C, and F1. Sample subtypes were determined by neighbor
      joining phylogenetic analysis with a Kimura's two-parameter correction. RESULTS:
      A high prevalence of polymorphisms unrelated to resistance was observed. Among
      ENF-untreated patients, 16% showed mutations related with resistance. Among
      patients in ENF treatment, 50% had resistance-related mutations. Overall, 17% of
      all isolates showed the N42S polymorphism related to ENF hypersusceptibility. The
      presence of ENF resistance mutations in the group of treated patients reduced
      viral load. The V38A substitution was the most frequent among treatment
      experienced patients followed by the G36D/E, N42D, and V38M substitutions.
      CONCLUSIONS: The V38A substitution in the gp41 HR region was the most common
      resistance mutation among ENF-treated patients and was associated with increased
      viral load.

PMID- 21857320
TI  - Coinfection by HIV-1 and human lymphotropic virus type 1 in Brazilian children is
      strongly associated with a shorter survival time.
AB  - Coinfection by HIV-1 and human lymphotropic virus type 1 is a frequent finding in
      South America, the Caribbean and Africa, and its prevalence varies from 4% to 16%
      according to the available reports. Although the impact of coinfection on HIV
      disease is still controversial, there is evidence supporting the contention that
      it can affect the natural history of both infections. No information is available
      on coinfection in children. In a nested case-control study, we evaluated 35
      coinfected children matched by age, gender, and time of diagnosis to HIV
      monoinfected control subjects. At the first evaluation, coinfected children were
      more likely to present any signs and symptoms of disease (P < 0.001) than
      monoinfected ones despite having significantly higher CD4 cells count (1429 +/-
      608 vs 928 +/- 768 cells/mm; P = 0.003). The proportion of deaths was higher
      (80%) for coinfected children than for HIV-1-infected ones (20%; relative risk,
      2.1; 95% confidence interval, 1.4-3.1; P = 0.01). Survival was also significantly
      shorter for coinfected children (P = 0.001). Coinfection by HIV-1 and human
      lymphotropic virus type 1 in Brazilian children was strongly associated with
      higher mortality and shorter survival time despite coinfected patients having a
      higher baseline CD4 cells count.

PMID- 21857319
TI  - The impact of human T-cell lymphotropic virus I infection on clinical and
      immunologic outcomes in patients coinfected with HIV and hepatitis C virus.
AB  - BACKGROUND: HIV, hepatitis C (HCV), and human T-cell lymphotropic virus I (HTLV
      1) are associated with high global burdens of disease, notably in resource-poor
      locales. They share similar routes of transmission and cause chronic infections
      with associated morbidity. We performed a cross-sectional study to assess the
      impact of HTLV-1 infection on clinical outcomes in HIV/HCV-coinfected patients.
      METHODS: We enrolled 102 (72.3%) with HIV/HCV coinfection (Group 1) and 39
      (27.7%) triply infected with HIV, HCV, and HTLV-1 (Group 2). We reviewed medical
      records of two groups of patients followed in two outpatients services in
      Salvador, Brazil. We collected and compared demographic, behavioral-related
      information, immunologic, virologic, and histologic parameters for HIV-1 and HCV
      infection. RESULTS: Demographics, virologic, and immunologic characteristics were
      similar in the two groups; a higher proportion of triply infected patients (Group
      2) reported any history of injection drug use compared with dually infected
      (Group 1) patients (75% vs 45.8%; P = 0.003). No differences were seen between
      groups in HIV clinical outcomes (CD4 count and viral load). Alanine
      aminotransferase levels were significantly higher in HIV/HCV-coinfected patients
      (P = 0.045). Liver fibrosis damage based on Metavir scores was similar between
      groups (0.97) but was worse with lower CD4 cell count (under 200 cells/mm) (P =
      0.01). CONCLUSIONS: HIV/HTLV-1 and HIV/HCV coinfections may worsen clinical
      related outcomes, but virologic and immunologic outcomes were similar in both
      groups. Hepatic measures were worse in patients with more severe
      immunosuppression.

PMID- 21857321
TI  - Cervical cytology and histopathologic abnormalities in women living with AIDS in
      Sao Paulo, Brazil.
AB  - BACKGROUND: Women living with HIV/AIDS present with a higher prevalence of human
      papillomavirus (HPV) infection, higher rates of squamous intraepithelial lesions,
      and are more susceptible to invasive cervical carcinoma progression. OBJECTIVE:
      We assessed the frequency of precursory cervical lesions of cancer and its risk
      factors for women living with HIV/AIDS. METHODS: Sociodemographic, clinical,
      behavioral, and laboratory data were collected from medical records from 2008 to
      2009 and analyzed using forward stepwise logistic regression. RESULTS: Medical
      records of 631 women were reviewed; mean age at AIDS diagnosis was 34 years old
      (interquartile range = 29-40 years old), 32% were <16 years old at first sexual
      intercourse; 61% had <=5 sexual partners during life; 43% had been living with
      AIDS for >=9 years; 47% reported previous sexually transmitted infections; 44%
      presented with HPV infection; and 10% presented with high squamous
      intraepithelial lesions. Presenting high squamous intraepithelial lesions was
      significantly associated with home district Human Development Index, age at AIDS
      diagnosis (>40 years old), time of AIDS diagnosis (>8 years), CD4 cell count
      <350/mm, and HPV infection. CONCLUSIONS: Frequent squamous intraepithelial
      neoplasia in these women shows the importance of gynecologic examinations in
      routine care and follow-up required by those who present with cervical lesions.

PMID- 21857322
TI  - Anal HPV prevalence and associated factors among HIV-seropositive men under
      antiretroviral treatment in Brazil.
AB  - BACKGROUND: The incidence of anal cancer has increased in developed countries.
      There is evidence that high-grade anal intraepithelial neoplasia and anal cancer
      are both linked to some human papillomavirus (HPV) infections. There are scarce
      data on anal cancer or male anal HPV infection in Brazil. OBJECTIVE: The purpose
      of this study was to assess the prevalence of anal HPV infection and associated
      risk factors, stratified by oncogenic and nononcogenic types, in a sample of HIV
      seropositive men in Brazil. METHODS: Multicenter cross-sectional study of HIV
      seropositive male patients attending public AIDS clinics in urban Brazil.
      Participants were interviewed for sociodemographic and behavioral
      characteristics. Anal HPV specimens were collected with a moistened Dacron swab
      inserted into the anal and stored in ThinPrep solution. HPV DNA-positive samples
      were typed by dot-blot hybridization. The prevalences of oncogenic and
      nononcogenic HPV types were calculated and multinomial logistic regression was
      used to assess independent predictors of HPV infection. RESULTS: : Among 445 men,
      65.6% were positive for HPV DNA in the anal canal. Oncogenic types were detected
      in 40.7%. Logistic regression indicated that lifetime history of sexual
      intercourse only with men or with men and women; receptive anal intercourse in
      the last 12 months; and CD4 lymphocyte count below 200 cells per cubic millimeter
      were independently associated with the detection of anal HPV infection.
      CONCLUSIONS: The high prevalence of anal HPV infection in this cross-sectional
      study underscores the need for studying and implementing screening programs of
      high-risk groups in Brazil.

PMID- 21857323
TI  - Socially supportive activity inventory: reliability and validity of a social
      activity instrument for long-term care institutions.
AB  - BACKGROUND: : Diverse social and recreational activities in elder care
      institutions have been provided to enrich a person's mental well-being amidst
      what is a relatively monotonous life. However, few instruments that measure the
      social activities of long-term care residents are available. PURPOSE: : This
      study was designed to develop a culturally sensitive instrument (Socially
      Supportive Activity Inventory, SSAI) to assess quantity and quality of social
      activities for long-term care institutions and validate the instrument's
      psychometric properties. METHODS: : The SSAI was developed on the basis of the
      social support theory, a synthesis of literature, and Taiwanese cultural mores.
      The instrument was rigorously subjected to a two-stage process to evaluate its
      reliability and validity. In Stage 1, six experts from diverse backgrounds were
      recruited to evaluate instrument items and estimate the content validity of the
      instrument using a content validity questionnaire. Items were modified and
      refined on the basis of the responses of the expert panel and a set of criteria.
      After obtaining approval from a university institutional review board, in the
      second stage of evaluating test-retest reliability, a convenience sample of 10
      Taiwanese institutionalized elders in a pilot study, recruited from a nursing
      home, completed the revised instrument at two separate times over 2 weeks.
      RESULTS: : Results showed a content validity of .96. Test-retest reliability from
      a sample of 10 participants yielded stability coefficients of .76-1.00. The
      stability coefficient was 1.00 for the component of frequency, .76-1.00 for the
      component of meaningfulness, and .78-1.00 for the component of enjoyment.
      CONCLUSION: : The SSAI is a highly relevant and reliable culturally based
      instrument that can measure social activity in long-term care facilities. Because
      of the pilot nature of this study, future directions include further exploration
      of the SSAI instrument's psychometric properties. This should be done by
      enlarging the sample size to include more long-term care facilities and
      individual participants. Future studies can utilize diverse measures of social
      activity for comparison and validation of the SSAI.

PMID- 21857324
TI  - The sleep log and actigraphy: congruency of measurement results for heart failure
      patients.
AB  - BACKGROUND: : Quality of life in patients with heart failure (HF) can be
      significantly impacted by poor sleep and its daytime consequences. As more
      attention is being paid to the sleep problems of HF patients, it is important to
      evaluate the degree of congruence between subjective and objective sleep
      measurements in this patient group. PURPOSE: : This study was developed to
      evaluate the congruence between sleep parameters as measured using a wrist-worn
      ActiGraph and a daily sleep log in patients with stable HF. METHODS: : Forty
      three HF patients aged 40-92 years served as subjects. Sleep parameters were
      derived from actigraphy and a daily sleep log by averaging scores for 7 nights.
      RESULTS: : There were significant differences in wake time after sleep onset
      (WASO) and total sleep time between the sleep log and the ActiGraph (both ps <
      .001). Neither WASO nor sleep onset latency, both derived from the sleep log,
      correlated significantly with actigraphy variables. The mean bias for WASO and
      total sleep time between methods was 54.1 min (SD = 47.5 min) and 109.3 min (SD =
      91.68 min) as assessed using a Bland-Altman analysis. A majority (83.7%) of
      participants experienced sleep disturbances as assessed by actigraphy. However,
      fewer (53.5%) had sleep disturbances as assessed using the sleep log. CONCLUSION:
      : A considerable degree of incongruence between actigraphy- and sleep log-derived
      measures of sleep exists in patients with stable HF.

PMID- 21857325
TI  - Continuous quality improvement of nursing care: case study of a clinical pathway
      revision for cardiac catheterization.
AB  - BACKGROUND: : Taiwan's Bureau of National Health Insurance (BNHI) has been
      gradually introducing Taiwan diagnosis related groups (Tw-DRGs) for inpatient
      cases since 2010. Challenged to adapt to payment system changes, hospitals must
      implement necessary management control systems or measures to maintain both
      fiscal soundness and medical care quality. PURPOSE: : This study investigated the
      outcome of management participation in work to revise cardiac catheterization
      clinical pathway operating procedures. METHODS: : BNHI-qualified cases for Tw
      DRGs 125 payment principles were recruited as study subjects to revise the
      cardiac catheterization clinical pathway. Researchers compared pre- and
      postrevision values in terms of mean medical care fees, patient volumes,
      healthcare quality, and length of hospital stay, as well as financial risk.
      RESULTS: : Significant differences were observed in precardiac catheterization
      nursing care completion rates, mean lengths of hospital stay, diagnosis numbers,
      surgical treatment numbers, and numbers of complications or comorbidities.
      Medical utilization was also significantly lower (p < .05) after revision
      implementation. CONCLUSIONS: : Clinical pathway revision involves organization,
      procedural flows, and performance management. The revision successfully improved
      hospital finances and promoted medical care quality.

PMID- 21857326
TI  - Translating and adapting mental health service outcome measurements for use in
      Taiwan.
AB  - BACKGROUND: : Healthcare providers must deliver efficient and cost-effective care
      while continuously assessing user-focused outcomes to make appropriate
      improvements. Patient satisfaction is an important variable in the evaluation of
      psychiatric services, which complements the measurement of other outcome
      variables. Previous research suggests a strong link between satisfaction and the
      effectiveness of patient care. PURPOSE: : Few international standard outcome
      measurements have been used in Taiwan to measure patient satisfaction with mental
      health services. In this study, a satisfaction survey instrument suited to
      Taiwan's cultural mores was developed. METHODS: : The researcher selected the
      Verona Service Satisfaction Scale (VSSS) as an optimal measurement instrument.
      The approach of the European Psychiatric Services Input Linked to Outcome Domains
      and Needs Study Group was adopted to translate and adapt an English version of a
      psychiatric-setting-specific, validated, and multidimensional satisfaction scale
      into a culturally appropriate traditional Chinese version scale. RESULTS: : This
      study used particular translation protocols to confirm the validity of the
      Chinese version of the VSSS questionnaire. Pilot study results demonstrate the
      adequate reliability of the Chinese version of the VSSS, which achieved results
      similar to those of the original-language European Psychiatric Services Input
      Linked to Outcome Domains and Needs Study. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:
      : In Taiwan, patient satisfaction with received care has risen concurrently with
      rising concerns regarding the future development of healthcare services. The
      intention of this project was to develop and use such outcome measurement in
      future research to gain insights into how to better value the expressed opinions
      and input of service users and develop services better tailored to Taiwan's
      cultural mores and in line with national mental health system requirements.

PMID- 21857327
TI  - Impact of the life review program on elders with dementia: a preliminary study at
      a day care center in southern Taiwan.
AB  - BACKGROUND: : Life review, a type of reminiscence therapy, assists participants
      to seek personal value in order to enhance social status and maintain a high
      quality of life (QOL). PURPOSE: : This study aimed to examine the impact of an
      adaptive life review program (LRP) on perceived QOL in elders with mild to
      moderate dementia at a day care center and assess the effect, if any, of
      different cognitive impairment levels on intervention outcome. METHODS: : This
      pre-experimental design used a single group of seven subjects for pretest and
      posttest and purposive sampling at a 2-week interval. Researchers administered to
      each subject a 10-day therapeutic recreation program modified from Tabourne's
      (1991) LRP. RESULTS: : Posttest results found no statistically significant
      improvements. However, subjects reported higher mean scores of perceived QOL as
      measured by the 36-Item Short Form Health Survey. This finding indicated a trend
      of improving physical and mental health after the intervention. In addition,
      subjects with moderate cognitive impairment reported a higher improvement in
      physical health perception than did subjects with mild cognitive impairment.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: : Future research should include a larger
      sample size and a longer period of intervention and adopt multiple dimensions of
      QOL measurements to increase research rigor. Suggestions from this study can be
      used to improve the LRP.

PMID- 21857328
TI  - The lived experiences of fathers in cross-national marriages.
AB  - BACKGROUND: : Research on cross-national marriages in Taiwan has concentrated on
      development and adaptation issues related to the children of such relationships.
      Taiwan has seen a dramatic increase in immigration and cultural diversity over
      the past 2 decades. Understanding the dynamics of cross-national families from
      initial courtship through marriage and having and raising children is, thus,
      important. Little research has been done on the role or caring experiences of the
      father in cross-national families. PURPOSE: : This study used the lived
      experiences of fathers in cross-national marriages with children to explore the
      essence of their role. METHODS: : Colaizzi's phenomenological approach was used
      to investigate subject experiences. Subjects were purposively chosen from a
      general hospital in Taiwan. Subject selection criteria included being a father in
      a cross-national marriage, having a child born in that marriage and the child was
      free of major health problems. Eleven fathers participated in the study. Sample
      size was determined by the saturation principle of phenomenology. Data collected
      included family demographic characteristics and open interview information.
      Narrative data were analyzed using Colaizzi's phenomenological approach.
      Trustworthiness was examined using principles from Lincoln and Guba. RESULTS: :
      Subject experiences concentrated on four themes: (a)achievement of a life
      mission, (b) marital difficulties, (c) activities external to the framework of
      family life, and (d) majesty and responsibility. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: : Fathers in the childbearing stage of cross-national marriages have
      experienced preparation for marriage, constructed a marital life together
      including relationships with other family members, and experienced the majesty
      and responsibility associated with their marriage. These findings provide
      knowledge for nurses that will help further enhance the role of fathers while
      developing and promoting family health within this subpopulation in Taiwan.

PMID- 21857329
TI  - The skill mix model: a preliminary study of changing nurse role functions in
      Taiwan.
AB  - BACKGROUND: : Nursing shortage is a critical problem worldwide. Using nurse aides
      (NAs) within a skill mix model has been applied in the healthcare delivery system
      as a strategy to improve nursing workforce shortages. PURPOSE: : The purpose of
      this study was to investigate changes in nurse perceptions of their role
      functions under the skill mix model in Taiwan. METHODS: : This was a cross
      sectional designed study that employed a structured questionnaire. Participants
      included 38 registered nurses from three medical wards in three hospitals that
      had implemented the skill mix model for 6 months. The questionnaire gathered data
      on participant demographics, perceptions on the role functions, role and job
      satisfaction of nurses, and patient care quality. Nurses' role functions were
      grouped into independent, dependent, and interdependent categories. RESULTS: :
      Results demonstrate that nurses' perceptions of independent and interdependent
      role function have changed since the implementation of the skill mix model. The
      most significant role changes in the independent function category included the
      nurse as educator of NAs, supervisor for patient care, and evaluator for nursing
      care outcomes. The most significant role changes in the interdependent function
      category included the nurse as integrator of nursing work and coordinator of the
      healthcare team. Nurses' perceived changes increase in repetitive confirmation of
      patient conditions and patient care quality. CONCLUSIONS: : This study revealed
      that nurses working in skill mix model environments need more authority to
      delegate and educate NAs and to supervise and integrate nursing care. Study
      results may serve as a reference for hospital nursing practice in Taiwan.

PMID- 21857330
TI  - A school-based health promotion program for stressed nursing students in Taiwan.
AB  - BACKGROUND: : Nursing students face both clinical and academic stress. Extensive
      theoretical and research literature suggests that peer support and regular
      exercise are critically important and can efficiently manage stress for nursing
      students. PURPOSE: : The purpose of this study was to investigate the effect of a
      school-based health promotion program in a group physical activity intervention
      and peer support program for stressed nursing students. METHODS: : This study
      used a quasi-experimental design to collect information and collected data from a
      stress questionnaire, semistructured questionnaire, and group discussion.
      Participants included 77 nursing students at an institute of technology in
      northern Taiwan. Participants were randomly assigned into experimental (n = 37)
      and control (n = 40) groups. Program duration was 16 weeks. Participants were
      selected based on their assessment results as having moderate or severe levels of
      stress. All participants in the experimental group took part in a group physical
      activity for 30 minutes three times a week. Eight weeks later, the researcher
      invited each group to discuss their feelings and stress coping strategies. Both
      groups completed pretest and posttest stress questionnaires. Quantitative data
      were analyzed using SPSS 14.0 Statistical Package for Windows, and qualitative
      data from each group discussion were analyzed using content analysis. RESULTS: :
      Results revealed that level of stress was statistically decreased in the
      experimental group. Posttest stress levels were significantly different in
      experimental and control groups. The results suggested that students who
      participated in the intervention had less stress than did those in the control
      group after the intervention. Those in the experimental group held positive views
      of peer support and physical activity. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: :
      The results of this study confirmed the efficacy of school-based health promotion
      programs in reducing stress in nursing students. Findings may provide educators
      with information to assist their developing effective health promotion programs
      to manage stress for their students. This study can also help students develop
      personal coping strategies through physical activity and peer support.

PMID- 21857331
TI  - Trends in nursing education.
AB  - Many new nursing leaders assuming deanships, assistant deanships, or interim
      deanships have limited education, experience, or background to prepare them for
      the job. To assist new deans and those aspiring to be deans, the authors of this
      department, 2 deans, offer survival tips based on their experiences and insights.
      They address common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 21857332
TI  - The use of simulation in medication calculation instruction: a pilot study.
AB  - Mathematical competency is essential to students' understanding of medication
      calculation. A simulation instruction improved students' medication calculation
      test grades from baseline.

PMID- 21857333
TI  - Twitter in the classroom: twenty-first century flash cards.

PMID- 21857334
TI  - Antiretroviral HIV treatment decreases heterosexual transmission.

PMID- 21857335
TI  - Development and testing of the patient safety test: current concepts.
AB  - To explore patient safety concepts applicable to clinical teaching in the current
      healthcare environment, the Patient Safety Test was created. Patient Safety Test
      assists nursing faculty members to assess their knowledge of safety and quality
      information. The authors discussed test development, implementation, and results.

PMID- 21857336
TI  - Information technology as a tool to facilitate the academic accreditation
      process.
AB  - The site visit is a crucial component of the academic accreditation process. Many
      nursing education programs have adopted electronic processes for document
      management and course delivery. In this article, the authors describe reasons for
      using an electronic resource room, changes made in document management systems,
      methods to provide electronic documentation access to site evaluators, and ways
      to link decisions directly to supporting evidence. Significant advantages were
      realized from the electronic resource room.

PMID- 21857337
TI  - Useful resource for teaching infection control provided by HHS.

PMID- 21857338
TI  - Clinical peer mentoring: partnering BSN seniors and sophomores on a dedicated
      education unit.
AB  - The authors describe a clinical peer mentoring (CPM) program that partnered 16
      pairs of senior (mentors) and sophomore (novices) BSN students to provide patient
      care on a dedicated education unit at a VA Medical Center. Situated learning
      theory and Tanner's Clinical Judgment Model provided frameworks for CPM
      implementation. Survey findings suggested novices and mentors perceived
      improvements in self-confidence, prioritization, time management, clinical
      judgment, and evidence-based practice use. Many mentors spontaneously expressed
      an interest in becoming a preceptor or nurse educator.

PMID- 21857339
TI  - Solving the nurse faculty shortage: exploring retention issues.
AB  - Researchers have explored reasons why nurse faculty leave academia, but few have
      focused on factors that encourage them to stay. Using Herzberg's Motivation
      Hygiene Theory, an online cross-sectional survey was completed by 1,171 tenured
      nurse faculty nationwide. Factor analysis revealed that the most significant
      factor influencing retention was professional satisfaction with faculty identity,
      including the ability to shape nursing practice. Academia may benefit by
      considering these factors to promote nurse faculty retention.

PMID- 21857340
TI  - A senior internship: facilitating the transition to nursing practice.
AB  - Nursing students are not afforded the opportunity to take a full patient
      assignment before transitioning into practice. It then often takes students
      months to feel comfortable caring for more than 2 patients once in practice. To
      assist students with transition-into-practice issues, the authors discuss a
      senior internship where students work one-to-one with an expert nurse, becoming
      acclimated to taking a full patient assignment.

PMID- 21857341
TI  - NIH working to put obesity research into practice.

PMID- 21857342
TI  - We are different: learning needs of accelerated second-degree nursing students.
AB  - In this study, the authors explored the perceptions of effective teaching
      learning strategies from the perspective of graduates of a second-degree
      prelicensure nursing program. Data were collected using interviews and analyzed
      using qualitative description. Seven themes were identified. These findings
      provide a unique perspective in identifying teaching strategies for use with
      these students and may provide insight and direction to others who have
      considered or are considering second-degree prelicensure programs.

PMID- 21857343
TI  - AACN resources to facilitate integration of the essentials of master's education
      in nursing.

PMID- 21857344
TI  - Bridging the theory-practice gap: a practice-relevant research course for RN to
      BSN students.
AB  - Wanting to create passion for research and evidence-based practice (EBP), the
      authors describe how a nursing instructor and the director for research and EBP
      in a community hospital partnered together to teach a practice-relevant research
      course for RN to BSN students. Students participated in the steps of the EBP
      process and presented formal reports in class of their EBP project results. One
      student described her research experience as awesome-evidence that this course
      bridged the theory-practice gap.

PMID- 21857345
TI  - Take the civility challenge: how partnership practices can turn toxic workplaces
      terrific.
AB  - Terrific or toxic? If your workplace is like that of 90% of the nurse educators
      surveyed by the author, conflicted interactions with colleagues and
      administrators are draining your joy. This article shares 2 exemplars that
      illustrate how mutually beneficial partnerships between faculty colleagues turned
      toxic workplaces terrific. After a hands-on introduction to a set of evidence
      based partnership practices, you will be ready to take the civility challenge by
      negotiating conscious and contracted collaborations that can turn your workplace
      terrific, 1 partnership at a time.

PMID- 21857346
TI  - Experience and education is paying off for nurses.

PMID- 21857347
TI  - Open versus laparoscopic pelvic lymph node dissection in early stage cervical
      cancer: no difference in surgical or disease outcome.
AB  - OBJECTIVE: This study aimed to investigate in a retrospective study the effect of
      laparoscopic surgery, introduced in our center in 1994 as part of the standard
      treatment of early stage cervical cancer, on surgical and disease outcomes.
      PATIENTS AND METHODS: A total of 169 women with cervical carcinoma stage IB1 (n =
      150) or IB2 (n = 19) were included in the study. Seventy-six patients who
      underwent laparoscopic pelvic lymph node dissection (LPLND), followed either by
      open radical hysterectomy (n = 63) or, in case of positive lymph nodes, by
      primary chemoradiation (n = 13), were compared with an historic cohort of 93
      patients who underwent a fully open, traditional Wertheim-Meigs procedure (WM).
      Recorded clinical characteristics of patients included age, International
      Federation of Gynecology and Obstetrics stage, histologic diagnosis,
      differentiation grade, tumor diameter, lymph node status, and adjuvant therapy.
      Operation time; lymph node yield; intraoperative, early, and late complications;
      site of recurrences; and disease-free and overall survival rates were analyzed
      and compared between groups. RESULTS: Clinical characteristics did not differ
      between groups. Duration of total surgery time was longer in patients with LPLND
      followed by open radical hysterectomy compared with that in the WM group (P <
      0.001). In patients with negative lymph nodes (n = 129), the number of resected
      nodes was higher (P = 0.002) in the LPLND (median, 26 nodes; range, 8-55 nodes)
      than in the WM group (median, 21 nodes; range, 7-50 nodes). In patients with
      positive lymph nodes (n = 40), no significant difference in the number of
      resected lymph nodes between the 2 groups (P = 0.904) was found. Intraoperative,
      early, and late complications did not differ between the 2 surgical procedures.
      The number of locoregional recurrences, but not of distant metastases, was
      significantly higher (P = 0.018) in the WM group compared with the LPLND group.
      No difference in disease-free or disease-specific survival was found between the
      LPLND and WM group, neither with nor without adjuvant or primary
      (chemo)radiation. A benefit in disease-free survival (P = 0.044), but not in
      disease-specific survival (P = 0.070), was found in the LPLND compared with the
      WM group in those patients who received adjuvant therapy or primary
      chemoradiation. CONCLUSIONS: Introduction of a laparoscopic procedure in the
      surgical staging and treatment of cervical cancer patients did not have a
      detrimental effect on surgical or disease outcome, and this can be safely applied
      to the treatment of early stage cervical cancer.

PMID- 21857348
TI  - A comparison of radical vaginal hysterectomy combined with extraperitoneal or
      laparoscopic pelvic lymphadenectomy in the treatment of cervical cancer.
AB  - BACKGROUND: The use of radical vaginal hysterectomy in the treatment of cervical
      cancer is associated with lower morbidity and a similar cure rate when compared
      with the abdominal approach. The present study reports a case series of radical
      vaginal hysterectomy followed by extraperitoneal (Mitra) or video-laparoscopic
      (VLP) lymphadenectomy, with comparison of the 2 techniques. METHODS: Twenty-five
      patients with cervical carcinoma (stages IA1 to IIA) were submitted to radical
      vaginal hysterectomy and extraperitoneal or laparoscopic lymphadenectomy.
      RESULTS: The Mitra technique was used in 17 cases, and VLP was used in 8.
      Seventeen patients presented minor postoperative complications. The number of
      resected lymph nodes was similar with both techniques (median of 14 with VLP vs.
      21 with Mitra) (P = 0.215). The duration of surgery in the VLP group (mean, 339
      minutes) was shorter than that of the Mitra group (mean, 421 minutes) (P =
      0.015). CONCLUSIONS: The results obtained with both techniques are similar to
      those reported in the literature. The duration of extraperitoneal lymphadenectomy
      was longer than that of VLP lymphadenectomy. There were no differences between
      the 2 techniques concerning the number of resected lymph nodes and hospital stay.

PMID- 21857349
TI  - Australian gay men who have taken nonoccupational postexposure prophylaxis for
      HIV are in need of effective HIV prevention methods.
AB  - BACKGROUND: Gay men who request nonoccupational postexposure prophylaxis (PEP)
      may seek preexposure prophylaxis (PrEP) should this become available. We explored
      trends and predictors of PEP use among Australian gay men to inform future
      biomedical prevention programs. METHODS: We used 2001-2010 data from Gay
      Community Periodic Surveys in 3 Eastern Australian states and assessed PEP
      awareness and use in the 6 months before each survey, and among HIV-uninfected
      men in all surveys predictors of PEP use. Analytical methods included chi-square
      test for trend and multivariate log-binomial estimation of associations. RESULTS:
      The awareness of PEP significantly increased from 23% in 2001 to 64% in 2010. PEP
      use also increased from 2.3% to 3.9%, respectively. PEP use was significantly
      associated with being in a regular relationship with an HIV-serodiscordant
      partner, higher number of sex partners, engaging in anal intercourse with casual
      partners, and regularly testing for HIV/sexually transmitted infections. However,
      fewer than 8% of men who engaged in these practices reported PEP use.
      CONCLUSIONS: Our findings highlight the profiles of current PEP users: men in HIV
      serodiscordant relationships, and men having high numbers of casual partners and
      unprotected anal intercourse with them. These men are in need of effective HIV
      prevention strategies and may be receptive to preexposure prophylaxis in the
      future. Presently, targeted HIV education to improve risk assessment skills may
      prevent some seroconversions through the appropriate use of PEP.

PMID- 21857350
TI  - Differences in risk behaviors and partnership patterns between younger and older
      men who have sex with men in New York City.
AB  - BACKGROUND: Men who have sex with men (MSM) account for a higher proportion of
      HIV diagnoses than any other risk group in the United States. Given that in NYC
      MSM younger than 30 years represent a growing proportion of new diagnoses among
      MSM, we examined differences between MSM by age. METHODS: We analyzed NYC
      surveillance and partner services (PS) data for MSM newly diagnosed with HIV from
      January 2007 to December 2008. We compared demographics, HIV-related risk
      behaviors, and sexual partner characteristics between younger MSM (<30 years old)
      (YMSM) and MSM >=30 years old. RESULTS: Three hundred and thirty-six MSM were
      interviewed for PS (180 YMSM and 156 older MSM). MSM were mostly black or
      Hispanic (91%). YMSM were more likely than older MSM to report gay sexual
      identity (70% vs. 58%, P < 0.01), and a recent sexually transmitted infection
      (29% vs. 15%, P < 0.01). More YMSM named >=1 male partner for HIV notification
      (66% vs. 36%, P < 0.01). YMSM were more likely than older MSM to name partners
      who were 5 or more years older (42% vs. 25%, P < 0.01). More YMSM tested for HIV
      at least once in the past 2 years than older MSM (66% vs. 40%, P < 0.01).
      DISCUSSION: Our study has identified important differences in HIV risk behaviors
      and sexual partnerships between YMSM and older MSM newly diagnosed with HIV. YMSM
      were more willing to provide the names of male sex partners for the purposes of
      partner notification than were older MSM, suggesting that PS may be particularly
      effective at identifying new cases of HIV.

PMID- 21857351
TI  - Men who have sex with men have a 140-fold higher risk for newly diagnosed HIV and
      syphilis compared with heterosexual men in New York City.
AB  - OBJECTIVES: To describe the population of men who have sex with men (MSM) in New
      York City, compare their demographics, risk behaviors, and new HIV and primary
      and secondary (P&S) syphilis rates with those of men who have sex with women
      (MSW), and examine trends in infection rates among MSM. DESIGN: Population
      denominators and demographic and behavioral data were obtained from population
      based surveys during 2005-2008. Numbers of new HIV and P&S syphilis diagnoses
      were extracted from city-wide disease surveillance registries. METHODS: We
      calculated overall, age-specific and race/ethnicity-specific case rates and rate
      ratios for MSM and MSW and analyzed trends in MSM rates by age and
      race/ethnicity. RESULTS: The average prevalence of male same-sex behavior during
      2005-2008 (5.0%; 95% CI: 4.5 to 5.6) differed by both age and race/ethnicity
      (2.3% among non-Hispanic black men; 7.4% among non-Hispanic white men). Compared
      with MSW, MSM differed significantly on all demographics and reported a higher
      prevalence of condom use at last sex (62.9% vs. 38.3%) and of past-year HIV
      testing (53.6% vs. 27.2%) but also more past-year sex partners. MSM HIV and P&S
      syphilis rates were 2526.9/100,000 and 707.0/100,000, each of which was over 140
      times MSW rates. Rates were highest among young and black MSM. Over 4 years, HIV
      rates more than doubled and P&S syphilis rates increased 6-fold among 18-year-old
      to 29-year-old MSM. CONCLUSIONS: The substantial population of MSM in New York
      City is at high risk for acquisition of sexually transmitted infections given
      high rates of newly diagnosed infections and ongoing risk behaviors. Intensified
      and innovative efforts to implement and evaluate prevention programs are
      required.

PMID- 21857352
TI  - Standardization and monitoring of laboratory performance and quality assurance by
      use of the less-sensitive HIV incidence assay: seven years of results.
AB  - BACKGROUND: The Performance Evaluation Program for HIV-1 incidence tests provided
      quality assurance services to laboratories conducting the serological testing
      algorithm for recent HIV seroconversion by use of a modified less-sensitive
      version of the Vironostika HIV-1 MicroElisa System assay. We report on the
      performance of the assay using proficiency testing and quality control materials
      tested from 2001 to 2008. METHODS: Two sets of 5 blinded serum panels using
      common calibration and quality control materials were tested. The mean, standard
      deviation, and coefficient of variation were calculated. Results were analyzed
      for misclassifications: false recent HIV infection errors (long-term infection
      classified as HIV infection less than 1 year), false long-term infection errors
      (HIV infection less than 1 year classified as long-term infection), and
      differences in standardized optical density means and variances over time.
      RESULTS: The false recent error rate was 1.26% (n = 2219). The false long-term
      error rate was 0.25% (n = 1618). No significant trends were observed for
      misclassification rates by year, and no significant trend in the standardized
      optical density over 7 years was observed. CONCLUSIONS: Laboratories using the
      less-sensitive Vironostika HIV-1 assay produced consistent results by use of a
      common calibrator and quality control materials.

PMID- 21857353
TI  - Loss to follow-up of stable antiretroviral therapy patients in a decentralized
      down-referral model of care in Johannesburg, South Africa.
AB  - A retrospective record review was conducted for patients down referred to primary
      health care facilities between 2007 and 2009 to assess the rate and reported
      reasons for loss to follow-up among stable antiretroviral patients in a down
      referral model of care in Johannesburg, South Africa. Missing patients were
      traced telephonically. Of 3361 patients down referred, 4.11% were lost to follow
      up. Most patients who were lost to follow-up were lost at the transfer stage
      between initiation and maintenance sites. Decentralization and nurse management
      of ART should be prioritized to increase access to and retention in HIV/AIDS
      care.

PMID- 21857355
TI  - Temporal trends in baseline characteristics and treatment outcomes of children
      starting antiretroviral treatment:  an analysis in four provinces in South
      Africa, 2004-2009.
AB  - BACKGROUND: Few studies describe temporal trends in pediatric antiretroviral
      treatment (ART) programs in sub-Saharan Africa. Adult studies show deteriorating
      patient retention in recent years. We describe temporal trends in baseline
      characteristics and treatment outcomes amongst ART-naive children between 2004
      and 2009 at 30 facilities in 4 South African provinces. METHODS: Linear trend in
      baseline parameters between annual enrolment cohorts was assessed. Corrected
      mortality estimates were calculated, correcting for deaths amongst those lost to
      follow-up using probability-weighted Kaplan-Meier functions. On-treatment
      immunologic changes were modelled using generalized estimating equations.
      RESULTS: Three thousand and seven children (median age 6.4 years) were included.
      Monthly enrollment increased from 1.9 children in 2004 to 106 in 2009.
      Proportions with severe baseline immunodeficiency decreased from 85.5% to 64.5%
      between 2004/2005 and 2009, P < 0.0005. Proportions with baseline World Health
      Organization clinical stages III and IV reduced from 72.9% to 49.0% between 2006
      and 2009, P < 0.0005. Later calendar cohorts had independently and progressively
      reduced on-treatment probabilities of severe immunodeficiency despite adjusting
      for baseline immunological status, adjusted odds ratio: 0.38 [confidence interval
      (CI): 0.26 to 0.55; P < 0.0005; 2008/2009 compared with 2004/2005]. After 24
      months, corrected mortality was 6.1% (CI: 5.1% to 7.3%) and loss to follow-up was
      6.8% (CI: 5.7% to 8.2%), with no deterioration amongst more recently enrolled
      cohorts (P = 0.50 and P = 0.55, respectively). After 4 years, program retention
      was 84.1% (CI: 80.9% to 86.7%). CONCLUSIONS: Childrens' baseline condition when
      starting ART has improved considerably. Improving immunological treatment
      outcomes, the high medium-term patient retention with lack of temporal
      deterioration despite rapid patient number increases, provide evidence that
      pediatric ART programs are increasingly effective for those accessing them.
      However, children must start treatment when younger, following current
      international guidelines.

PMID- 21857354
TI  - Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral
      therapy regimens in Lusaka, Zambia.
AB  - BACKGROUND: Although tenofovir (TDF) is a common component of antiretroviral
      therapy (ART), recent evidence suggests inferior outcomes when it is combined
      with nevirapine (NVP). METHODS: We compared outcomes among patients initiating
      TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV),
      zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized
      drug exposure by initial ART dispensation by a time-varying analysis that
      accounted for drug substitutions and by predominant exposure (>75% of drug
      dispensations) during an initial window period. Risks for death and program
      failure were estimated using Cox proportional hazard models. All regimens were
      compared with ZDV + 3TC + NVP. RESULTS: Between July 2007 and November 2010,
      18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on
      ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When
      exposure was categorized by initial prescription, patients on TDF + XTC + NVP
      [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06]
      had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an
      elevated risk for mortality when exposure was categorized as time-varying (AHR:
      1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days
      (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently
      observed across sensitivity analyses or when program failure was used as a
      secondary outcome. CONCLUSION: TDF + XTC + NVP was associated with higher
      mortality when compared with ZDV + 3TC + NVP but not consistently across
      sensitivity analyses. These findings may be explained in part by inherent
      limitations to our retrospective approach, including residual confounding.
      Further research is urgently needed to compare the effectiveness of ART regimens
      in use in resource-constrained settings.

PMID- 21857356
TI  - Providing immediate CD4 count results at HIV testing improves ART initiation.
AB  - BACKGROUND: In South Africa, CD4 count results are typically available within a
      week of testing. However, 35%-55% of newly diagnosed HIV-positive patients do not
      return for their CD4 results and therefore, do not access further care. We
      evaluated the impact of a CD4 count result and patient written information
      provided immediately after diagnosis on retention in care. METHODS: HIV-infected
      subjects were randomized to 3 arms; receipt of a CD4 result at time of HIV
      diagnosis, receipt of written information, and standard of care (CD4 collection
      after 1 week) or standard of care alone. The outcome of interest was enrollment
      for further care within 1 month for pre-antiretroviral therapy (ART) care or
      within 3 months for ART initiation. Secondary outcome was time taken from
      diagnosis to each stage of care pathway. Independent predictors of retention were
      assessed with multivariate analysis. RESULTS: Three hundred forty-four patients
      recruited, of which 64.5% were females with a median age of 30 years
      (interquartile range: 27-35). Subjects were similar in age, gender, CD4 count,
      education, and employment status. Providing CD4 results at HIV diagnosis
      increases the likelihood of reporting for ART initiation (risk ratio = 2.1; 95%
      confidence interval = 1.39 to 3.17) compared with standard of care. Written
      information only reduced the time to presentation for pre-ART care although
      increasing age was associated with retention. There was 49% attrition in the
      standard of care arms. CONCLUSIONS: Receipt of a CD4 count at the time of HIV
      testing increases ART initiation rates. Point-of-care diagnostics can be used to
      improve retention, but losses to pre-ART care remain high.

PMID- 21857358
TI  - Determinants of early and late mortality among HIV-infected individuals receiving
      home-based antiretroviral therapy in rural Uganda.
AB  - BACKGROUND: Up to 20% of people initiating antiretroviral therapy (ART) in sub
      Saharan Africa die during the first year of treatment. Understanding the clinical
      conditions associated with mortality could potentially lead to effective
      interventions to prevent these deaths. METHODS: We examined data from
      participants aged >=18 years in the Home-Based AIDS Care project in Tororo,
      Uganda, to describe mortality over time and to determine clinical conditions
      associated with death. Survival analysis was used to examine variables associated
      with mortality at baseline and during follow-up. RESULTS: A total of 112 (9.4%)
      deaths occurred in 1132 subjects (73% women) during a median of 3.0 years of ART.
      Mortality was 15.9 per 100 person-years during the first 3 months and declined to
      0.3 per 100 person-years beyond 24 months after ART initiation. Tuberculosis (TB)
      was the most common condition associated with death (21% of deaths), followed by
      Candida disease (15%). In 43% of deaths, no specific clinical diagnosis was
      identified. Deaths within 3 months after ART initiation were associated with
      World Health Organization clinical stage III or IV at baseline, diagnosis of TB
      at baseline, a diagnosis of a non-TB opportunistic infection in follow-up and a
      body mass index <=17 kg/m2 during follow-up. Mortality after 3 months of ART was
      associated with CD4 cell counts <200 cells per microliter, a diagnosis of TB or
      other opportunistic infection, adherence to therapy <95%, and low hemoglobin
      levels during follow-up. CONCLUSION: Potentially remediable conditions and
      preventable infections were associated with mortality while receiving ART in
      Uganda.

PMID- 21857357
TI  - Comparative effectiveness of initial antiretroviral therapy regimens: ACTG 5095
      and 5142 clinical trials relative to ART-CC cohort study.
AB  - BACKGROUND: The generalizability of antiretroviral therapy (ART) clinical trial
      efficacy findings to routine care settings is not well studied. We compared the
      relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial
      Group (ACTG) randomized controlled trials with that among patients receiving ART
      at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites. METHODS:
      Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG
      trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included.
      Virological failure (HIV-1 RNA >200 copies/mL) at 24 and 48 weeks, incident AIDS
      defining events and mortality were measured according to study design (ART-CC
      cohort vs. ACTG trial) and stratified by third drug [abacavir (ABC), efavirenz
      (EFV), and lopinavir/r (LPV/r)]. We used logistic regression to estimate and
      compare odds ratios (OR) for virological failure between different regimens and
      study designs, and used Cox models to estimate and compare hazard ratios for AIDS
      and death. RESULTS: Compared with patients receiving ABC, those receiving EFV had
      roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG
      5095 (OR = 0.53, 95% confidence interval: 0.36 to 0.79) and ART-CC (0.46, 0.37 to
      0.57). Virologic superiority of EFV (vs. ABC) seemed comparable in ART-CC and
      ACTG 5095 (ratio of ORs 0.86, 95% confidence interval: 0.54 to 1.35). Odds ratios
      for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in
      ACTG 5142 and ART-CC (ratio of ORs: 0.87, 0.45 to 1.69). CONCLUSIONS: Between ART
      regimen virologic efficacy of third drugs ABC, EFV, and LPV/r observed in the
      ACTG 5095 and 5142 trials seem generalizable to the routine care setting of ART
      CC clinical cohorts.

PMID- 21857359
TI  - Population pharmacokinetics of tenofovir in HIV-1-infected pediatric patients.
AB  - OBJECTIVES: To evaluate the pharmacokinetics of tenofovir in children and the
      influence of covariates [body weight (BW), age, cotreatments]. The main goal was
      then to suggest for the first time the dose of tenofovir disoproxil fumarate
      (TDF) to give in children. DESIGN/METHODS: Tenofovir concentrations were
      monitored on a routine basis and measured in 93 children aged 5 to 18 years; 283
      tenofovir plasma concentrations were used to perform a population pharmacokinetic
      analysis. RESULTS: A 2-compartment model adequately described the data. A BW
      allometric scaling was used; and the typical population estimates
      (interindividual variability), standardized for 70 kg, for apparent clearance,
      central and peripheral volume of distribution, intercompartmental clearance, and
      absorption rate constant, were 59.8 L.h-1 (0.48), 386 L (1.39), 666 L, 92.8 L.h-1
      and 0.43 h-1, respectively. TDF clearance increased significantly with BW and
      decreased with lopinavir/ritonavir (LPV/r) coadministration, thus these factors
      were used to propose doses for children. Dosing scheme, according BW and LPV/r
      coadministration were simulated to produce the same 24-hr exposure as adults
      after 300-mg TDF dose. CONCLUSIONS: Children without LPV/r should receive: 150 mg
      TDF from 20 to 30 kg, 225 mg TDF from 30 to 40 kg, and the adult dosage of 300 mg
      TDF over 40 kg. To avoid risk of renal toxicity, TDF dose should be decreased
      when coadministrated with LPV/r, children should receive 150 mg TDF from 20 to 40
      kg, 225 mg TDF from 40 to 55 kg, and the adult dosage of 300 mg TDF over 55 kg.

PMID- 21857361
TI  - Transactional sex amongst AIDS-orphaned and AIDS-affected adolescents predicted
      by abuse and extreme poverty.
AB  - OBJECTIVES: Little is known about impacts of familial AIDS on abuse and sexual
      health outcomes amongst adolescents. Objectives were to determine whether
      familial AIDS is: (1) associated with severe physical, emotional, and sexual
      abuse; (2) associated with transactional sexual exploitation; and (3) explore
      whether relationships between familial AIDS and transactional sex are mediated by
      extreme poverty and abuse. DESIGN: Adolescent self-report study in deprived South
      African communities. METHODS: A 2009 follow-up of a 2005 study achieved 71%
      retention (n = 723). The 2009 sample included AIDS-orphaned (n = 236), other
      orphaned (n = 231), and non-orphaned (n = 220) adolescents, whose primary
      caregivers were AIDS sick (n = 109), other sick (n = 147), and healthy (n = 220).
      Abuse and transactional sex were measured using widely used and validated self
      report measures. RESULTS: AIDS orphanhood and parental AIDS sickness predicted
      emotional and physical abuse and transactional sexual exploitation. Orphanhood or
      parental sickness by non-AIDS causes, and having healthy caregivers, did not
      predict any abuse outcomes. Adolescents "dually" affected by AIDS orphanhood and
      sickness showed a 3-fold likelihood of severe emotional and physical abuse and,
      amongst girls, a 6-fold likelihood of transactional sexual exploitation, compared
      with those in healthy families. Heightened risk of transactional sex amongst
      adolescents in AIDS-affected families was mediated by extreme poverty and abuse
      exposure. In combination, the effects of familial AIDS, food insecurity, and
      exposure to abuse raised prevalence of transactional sex amongst girls from 1% to
      57%. CONCLUSIONS: Adolescents from AIDS-affected families are highly vulnerable
      to severe physical and emotional abuse and transactional sex. This has
      implications for policy and programming in child protection and HIV prevention
      services.

PMID- 21857362
TI  - Recovery patterns in electroencephalographic global field power during maximal
      isometric force production.
AB  - In previous work, cortical activity decreased with fatigue following novel
      movements or small muscle group actions. These muscle actions, however, do not
      appear related to the cortical activity seen with biologically relevant and
      highly trained movement patterns (i.e., ingrained patterns). The cortical
      recovery response to ingrained patterns-and how it differs with altered load,
      speed, or volume - is unknown. The purpose of this balanced, within-group study
      was to investigate differences in cortical activity 24 hours after physically
      distinct variations of a highly trained squat exercise (n = 7, minimum 4 years
      resistance training experience). Four resistance protocols were chosen: rate of
      force development (PWR, 6 * 3 squat jumps at 30% of 1 repetition maximum [1RM]);
      magnitude of force development (FOR, 6 * 3 squat at 95% of 1RM); volume of force
      development (VOL, 6 * 10 squat at 80% of their 1RM); and control (CTRL, 6 sets
      unracking an empty bar). Twenty-four hours later, subjects performed a peak
      isometric squat while electroencephalographic and biochemical markers of exertion
      and fatigue were obtained. Global field power detected the quantity of activity
      superficial to motor regions. Waveforms of activity throughout the isometric
      squats were obtained and grand averages calculated to produce quantitative
      depictions of cortical activity. Significance was P <= 0.05. Peak isometric squat
      force was not statistically different 24 hours postexercise (Force [N]: PWR:
      2828.79 +/- 461.17; FOR: 2887.64 +/- 453.09; VOL: 2910.17 +/- 625.81; CTRL
      2768.53 +/- 374.85). Subjects produced similar and characteristic cortical
      activity patterns during isometric squats despite varying indices of fatigue.
      Differences were observed based upon the use or nonuse of aerobic endurance
      exercise in their training program. Patterns of activity in data seem to have
      emerged based on differences in training preference. Global Field Power (uV)
      during the isometric squat for PWR was 26.98 +/- 14.64; FOR 24.06 +/- 19.05; VOL
      23.05 +/- 13.37; and CTRL 15.78 +/- 8.11. Previous research suggests that
      cortical activity decreases with physical activity; however, despite substantial
      endocrine, perceptual, and biomechanical differences between protocols, cortical
      activity was not decreased below control during the performance of a maximal
      isometric squat 24 hours after various exercise protocols.

PMID- 21857360
TI  - Modeling interventions to assess HIV epidemic impact in Africa.

PMID- 21857363
TI  - The effect of training at the same time of day and tapering period on the diurnal
      variation of short exercise performances.
AB  - The purpose of this investigation was to assess the effects of training and
      tapering at the same time of the day on the diurnal variations of short exercise
      performances. Thirty-one physically active men underwent 12 weeks of lower
      extremity resistance training and 2 weeks of tapering. These subjects were
      matched and randomly assigned to a morning training group (MTG, training times
      0700-0800 hours, n = 10), an evening training group (ETG, training times 1700
      1800 hours, n = 11), and a control group (CG, completed all tests but did not
      train, n = 10). Muscular strength and power testing was conducted before (T0) and
      after 12 weeks of training (T1) and after 2 weeks of tapering (T2) in the morning
      (0700-0800 hours) and in the evening (1700-1800 hours). All morning and evening
      tests were performed in separate sessions (minimum interval = 36 hours) in a
      randomized design. In T0, the oral temperature and performances during the
      Wingate, vertical jump (squat jump and countermovement jump), and maximal
      voluntary contraction tests were higher in the evening than in the morning for
      all the groups. In T1, these diurnal variations were blunted in the MTG and
      persisted in the ETG and CG. In T2, the 2 weeks of tapering resulted in further
      time of day-specific adaptations and increases in short-term maximal
      performances. However, there was no significant difference in the relative
      increase between the MTG and the ETG after both training and tapering. From a
      practical point of view, if the time of competition is known, training and
      tapering sessions before a major competition must be conducted at the same time
      of the day at which one's critical performance is programmed. Moreover, if the
      time of the competition is not known, a tapering phase after resistance training
      program could be performed at any time of the day with the same benefit.

PMID- 21857364
TI  - Effects of polyester jerseys on psycho-physiological responses during exercise in
      a hot and moist environment.
AB  - Gonzales, BR, Hagin, V, Guillot, R, Placet, V, and Groslambert, A. Effects of
      polyester jerseys on psycho-physiological responses during exercise in a hot and
      moist environment. J Strength Cond Res 25(12): 3432-3438, 2011-With the general
      acceptance that extreme environments have a detrimental effect on
      thermoregulation and human performance, the aim of this study was to investigate
      the influence of 3 polyester jerseys with knits of different sizes on
      physiological and perceptual responses in trained cyclists during exercise
      performed in a hot and moist environment. Ten trained male cyclists (mean +/- SD,
      age: 29.1 +/- 8 years, height: 177.12 +/- 5 cm, body mass: 70.10 +/- 6 kg),
      performed 3 tests of 15 minutes at 150 W on a calibrated home trainer by randomly
      wearing jerseys with small knits (SK), medium knits, and large knits (LK). While
      exercising, the jersey and torso skin temperatures, perceived exertion and
      hotness, and heart rate (HR) were continuously recorded. The major results of
      this study showed that perceived hotness with LK was significantly lower (p <
      0.05) than with SK at minutes 10 (effect size [ES] = 1.18) and 12 (ES = 1.04) of
      exercise. The torso skin temperature with LK was significantly lower (p < 0.05)
      than with SK at minute 10 (ES = 0.84) and at minute 14 (ES = 0.81) of exercise,
      and the LK jersey temperature was significantly lower (p < 0.05) than with SK
      jerseys at minutes 12 (ES = 0.83) and 14 (ES = 0.90) of exercise. However, no
      significant difference was found in perceived exertion or HR. These results
      suggest that the use of polyester jerseys with larger knits could limit the drift
      of skin temperature and therefore increase the thermal comfort of cyclists during
      exercise performed in a hot and moist environment. Therefore, coaches are
      encouraged to take particular care that their athletes wear exercise-appropriate
      clothing in hot temperatures.

PMID- 21857365
TI  - The impact of hepatitis C coinfection on kidney disease related to human
      immunodeficiency virus (HIV): a biopsy study.
AB  - Approximately 1 in 4 individuals infected with the human immunodeficiency virus
      (HIV) in the United States is coinfected with the hepatitis C virus. Both
      conditions increase the risk for the development and progression of kidney
      disease. The effect, however, of coexisting HIV and hepatitis C infection on the
      spectrum and progression of kidney disease is not well known. To compare the
      clinical features, histopathologic kidney diagnoses, and proportion of
      individuals progressing to end-stage kidney disease (ESKD), we reviewed the
      clinical records of HIV-infected individuals with and without hepatitis C
      coinfection who underwent ultrasound-guided percutaneous kidney biopsies between
      February 7, 1995, and March 30, 2009.Of the 249 HIV-infected individuals included
      in this study, 58% were coinfected with hepatitis C. Coinfected individuals were
      older (mean age, 46 +/- 7 vs. 44 +/- 10 yr, respectively; p < 0.01) and more
      likely to have used illicit drugs (85% vs. 14%, respectively; p < 0.01) compared
      to HIV-infected individuals without hepatitis C. HIV-associated nephropathy was
      the most common histopathologic diagnosis in both groups. Immune-complex
      glomerulonephritides (ICGNs), including lupus-like nephritis, postinfectious
      glomerulonephritis, membranous glomerulopathy, membranoproliferative
      glomerulonephritis, IgA nephropathy, and nonspecific ICGNs, occurred more
      frequently in individuals coinfected with hepatitis C than in those not
      coinfected (22% vs. 11%, respectively; p = 0.02). Although the proportion of
      those who died was similar between the 2 groups, hepatitis C coinfection was
      independently associated with a greater risk of progression to ESKD (hazard
      ratio, 1.81; 95% confidence interval, 1.09-2.99; p = 0.02).The current study
      demonstrates that coinfection with hepatitis C in individuals infected with HIV
      predisposes these individuals to immune-complex glomerulonephritides and is
      associated with increased risk of ESKD in the biopsied population.

PMID- 21857366
TI  - Polyomavirus-associated nephropathy: a comparison of 2 different strategies for
      immunosuppression reduction.
AB  - Polyomavirus-associated nephropathy (PVAN) is an increasing cause of renal
      allograft dysfunction, but the optimal management of immunosuppression for these
      patients is unclear. We examined the clinical course of 58 patients with biopsy
      proven PVAN diagnosed from 1997 to 2008 at Johns Hopkins Medical Institutions.
      Immunosuppression management was analyzed as 2 different immunosuppression
      reduction strategies, the first centered on eliminating a single
      immunosuppressive drug and reducing the doses of all other immunosuppressive
      drugs (Strategy A, n = 40), compared with the second, centered on reducing the
      doses of all immunosuppressive drugs and eliminating none (Strategy B, n = 18).
      Primary outcome was graft failure, defined as a 50% reduction in estimated
      glomerular filtration rate, or the need for dialysis within 2 years of PVAN
      diagnosis. Graft failure developed in 17 (29%) patients during follow-up. In
      unadjusted and adjusted Cox models, both strategies of immunosuppression
      reduction had similar efficacy in preventing graft failure (hazard ratio [HR],
      0.61; 95% confidence interval, 0.18-2.06; p = 0.43). Rejection after PVAN
      occurred in 24 of 58 patients and was associated with a 3-fold higher risk of
      graft failure (HR, 2.99; p = 0.005). Ancillary therapies (cidofovir or
      leflunomide) were associated with a trend toward faster clearance of viremia (p =
      0.65) but were not predictive of outcome.In conclusion, the 2 strategies of
      immunosuppression reduction had similar efficacy in preventing graft failure.
      Post-PVAN rejection leads to graft failure. Early repeat allograft biopsy should
      be considered in the management of PVAN with persistent graft dysfunction.

PMID- 21857367
TI  - Systemic lupus erythematosus in northwestern Spain: a 20-year epidemiologic
      study.
AB  - To further investigate the epidemiology of systemic lupus erythematosus (SLE) in
      southern Europe, we assessed the incidence, prevalence, clinical spectrum of the
      disease, flares, and survival of patients diagnosed with SLE in the Lugo region
      of northwestern Spain. Between January 1987 and December 2006, 150 Lugo residents
      were diagnosed as having SLE according to the 1982 American College of
      Rheumatology criteria for the classification of SLE. Women outnumbered men (127
      [84.7%] vs. 23 [15.3%]). The mean age at the time of disease diagnosis was 46.1
      +/- 19.6 years. The mean follow-up from the time of disease diagnosis was 7.8 +/-
      4.5 years. The age- and sex-adjusted annual incidence rate over the 20-year study
      period was 3.6 (95% confidence interval [CI], 3.0-4.2) per 100,000 population
      aged 15 years and older. The overall annual incidence rate over the 20-year study
      period in women (5.9/100,000 population aged >= 15 yr; 95% CI, 4.9-7.0) was
      higher than in men (1.1/100,000 population aged >= 15 yr; 95% CI, 0.7-1.7) (p <
      0.001). By December 31, 2006, the overall age-adjusted SLE prevalence in the Lugo
      region for patients who fulfilled at least 4 of 1982 American College of
      Rheumatology criteria was 17.5 per 100,000 population aged 15 years and older
      (95% CI, 12.6-24.1). Prevalence in women (29.2/100,000 population aged >= 15 yr;
      95% CI, 20.0-40.7) was higher than in men (5.8/100,000 population aged >= 15 yr;
      95% CI, 2.0-12.0). The most frequent clinical manifestation was arthritis. As
      reported in population-based studies on SLE patients of European descent, renal
      disease was observed in only 27.3% of the patients. The rate of flares was
      0.084/year. A younger age and the presence of nephritis at the time of disease
      diagnosis were associated with the development of flares during the follow-up of
      Lugo patients. Compared with the general population the probability of survival
      in patients with SLE was significantly reduced (p = 0.04). In conclusion, the
      present study establishes a baseline estimate of the incidence and clinical
      spectrum of SLE in northwestern Spain. According to our results, the incidence of
      SLE in northwestern Spain is slightly higher than that reported in most European
      regions. Patients with SLE from northwestern Spain have a later average age onset
      and a lower frequency of nephritis than in the African-American population.
      However, our data show a reduced probability of survival in Spanish patients with
      SLE.

PMID- 21857368
TI  - Relationship of blood pressure and cardiovascular disease risk factors in
      normotensive middle-aged men.
AB  - We conducted this study to investigate whether subjects with high-normal systolic
      blood pressure (SBP) have an increased risk of cardiovascular disease (CVD)
      and/or diabetes compared to subjects with low-normal SBP, using metabolic
      syndrome (MetS) as a risk factor for future CVD/diabetes.The study included 6133
      apparently healthy Taiwanese men aged 40-65 years. All subjects were
      normotensive, and none took medication for any abnormal MetS component. To avoid
      the effect of age on blood pressure, we stratified patients first by age then by
      SBP (that is, low, middle, and high SBP). We pooled all the low, middle, and high
      SBP groups from the different age strata to create 3 larger groups (Group 1,
      Group 2, and Group 3, respectively). The MetS components in subjects with the
      lowest SBP (Group 1) were compared with those in the other 2 groups. All of the
      MetS components, except for high-density lipoprotein cholesterol (HDL-C), were
      significantly lower in Group 1. Thus, it was not surprising that Group 2 and
      Group 3 had significantly higher odds ratios for abnormal body mass index,
      fasting plasma glucose, low-density lipoprotein-cholesterol (LDL-C), and
      triglycerides than Group 1 (but not for HDL-C). Specifically, Group 3 had a 1.7
      fold higher odds ratio (p < 0.001) for having MetS than Group 1. Age, body mass
      index, fasting plasma glucose, LDL-C, and log triglycerides correlated
      significantly with SBP. In multivariate linear regression analysis, we found that
      only body mass index, fasting plasma glucose, and log triglycerides remained
      significantly related to SBP. Among them, body mass index had the highest beta
      value.In conclusion, the level of SBP was highly correlated with body mass index,
      fasting plasma glucose, and triglycerides in subjects with normotension. Although
      there is not a cause-and-effect relationship, the risk of CVD and diabetes was
      significantly associated with an elevation of SBP, even when the SBP remained
      within the normal range. Further studies are needed to determine whether
      normotensive subjects would benefit from medical management.

PMID- 21857369
TI  - Evaluation of a cell phone-based physical activity diary.
AB  - PURPOSE: Physical activity (PA) diaries reduce the recall error inherent in self
      reported PA but are burdensome. The purpose of this study was to compare a cell
      phone-based diary with a paper diary and examine the reliability and validity of
      the cell phone diary. METHODS: In a pilot study, 25 women and 23 men, age 45-65
      yr, completed cell phone and paper PA diaries 4 d.wk(-1) for three consecutive
      weeks and a user satisfaction survey. In the subsequent validation study, 623
      middle-age participants (52.5% women) were asked to complete the cell phone diary
      and wear an accelerometer for two 7-d periods, approximately 6 months apart. They
      also completed two PA questionnaires. Fitness, body mass index, and percent body
      fat were obtained as indirect validation criteria. RESULTS: Estimates of PA from
      the cell phone and paper diaries were similar (mean within person difference = 
      43.8 MET.min.d(-1) of total PA, SD = 360, P = 0.49, 7.4 min.d(-1) of moderate
      vigorous PA, SD = 66, P = 0.53). Users preferred the cell phone diary over the
      paper diary (59.6% vs 35.4%). In the subsequent study, intraclass correlations
      for the cell phone diary ranged from 0.55 for light PA to 0.63 for vigorous PA.
      Although PA estimates from the cell phone diary were generally significantly
      higher than those from the accelerometer and the questionnaires, correlations for
      moderate and vigorous PA were moderate (rho = 0.25-0.59 with the questionnaires
      and 0.27-0.35 with the accelerometer). The correlations between the cell phone
      diary and the indirect validation criteria were generally in the expected
      direction and of moderate magnitude. CONCLUSIONS: A cell phone-based PA diary is
      equivalent to a paper diary, acceptable to users, and a relatively reliable and
      valid approach to self-reported PA.

PMID- 21857370
TI  - Reliability of concussion history in former professional football players.
AB  - PURPOSE: The reliability of athletes to recall and self-report a concussion
      history has never been quantified. This study examined the reliability of the
      self-report concussion history measure and explored determinants of recall in the
      number of self-reported concussions in a group of retired professional football
      players. METHODS: In 2001, a short questionnaire was administered to a cohort of
      former professional football players to ascertain the number of self-reported
      concussions they sustained during their professional playing careers. In 2010,
      the same instrument was readministered to a subset (n = 899) of the original
      cohort to assess reliability. RESULTS: Overall reliability was moderate (weighted
      Cohen kappa = 0.48). The majority (62.1%) reported the same number of concussions
      in both administrations (2001 and 2010); 31.4% reported more concussions in the
      second administration. Compared with the "same number reported" group, the
      "greater number reported" group had more deficits in the second administration in
      their Short Form 36 physical health (composite score combining physical
      functioning, role physical, bodily pain, general health) and mental health (e.g.,
      composite score combining vitality, social functioning, role emotional) scales.
      CONCLUSIONS: The self-reported concussion history had moderate reliability in
      former professional football players, on the basis of two administrations of the
      same instrument, 9 yr apart. However, changes in health status may be
      differentially associated with recall of concussions.

PMID- 21857372
TI  - Mild dehydration does not reduce postexercise appetite or energy intake.
AB  - PURPOSE: It has now been established that exercise performed under various
      environmental conditions may affect acute energy intake and appetite-related
      hormones. The exact mechanism linking acute energy intake and exercise remains
      unknown, although indirect evidence suggests a possible role for hydration
      status. Therefore, the purpose of this study was to investigate the interaction
      of exercise and hydration status on subsequent energy intake and appetite-related
      hormones. METHODS: In a randomized, counterbalanced design, 10 physically active
      males completed three experimental trials in a fasted state: exercise when
      hydrated (0%-1% of body mass), exercise when dehydrated (-1% to -2% of body
      mass), and a hydrated resting control. Exercise consisted of treadmill running
      for 45 min at 70% VO2peak. Participants were then given access to a buffet-style
      breakfast from which they could consume ad libitum. Blood was sampled regularly
      during trials for appetite-related hormones. RESULTS: There were no significant
      differences in total energy intake between trials (P = 0.491); however, relative
      energy intake was significantly higher in the control (4839 +/- 415 kJ, P <
      0.001) compared to hydrated (1749 +/- 403 kJ) and dehydrated exercise (1656 +/-
      413 kJ) conditions. Exercise performed in a dehydrated state resulted in
      significantly lower concentrations of ghrelin compared with control (P = 0.045)
      and hydrated exercise conditions (P = 0.014). CONCLUSIONS: Exercise significantly
      decreased relative energy intake compared with resting control; however, energy
      intake (relative and total) was no different between the exercise conditions
      (dehydrated vs hydrated). Despite similar energy intake between trials, exercise
      in a dehydrated state resulted in a significantly lower concentration of ghrelin,
      a hormone responsible for stimulating appetite.

PMID- 21857371
TI  - Evaluation of arrhythmia scoring systems and exercise-induced cardioprotection.
AB  - INTRODUCTION: Exercise is protective against ventricular arrhythmias induced by
      ischemia (I), the condition of inadequate blood flow, and reperfusion (R), the
      reestablishment of blood flow. This protection is observed clinically and
      scientifically by decreased incidence in ECG abnormalities. Numerous scoring
      systems exist for the quantification of ventricular arrhythmia severity. On the
      basis of preventricular contractions, ventricular tachycardia, and ventricular
      fibrillation frequency, these scoring systems are intended to provide more robust
      ECG outcome indicators than individual arrhythmia variables. Scoring systems vary
      primarily on continuous versus discontinuous treatment of the data, which should
      be considered when matching these arrhythmia metrics to scientific applications.
      PURPOSE: The aim of this investigation was to evaluate seven ECG scoring systems
      in the assessment of ventricular arrhythmia severity after IR in male Sprague
      Dawley rats. METHODS: Animals remained sedentary or exercised (3 d of treadmill
      exercise for 60 min) before surgically induced IR. A subset of sedentary animals
      served as sham, undergoing surgical procedure without IR. ECGs were evaluated
      under blinded conditions by three trained individuals. Single arrhythmia data and
      the parametric score were analyzed by one-way ANOVA, whereas the Kruskal-Wallis
      was used to compare group means for all nonparametric scoring systems between
      groups. RESULTS: IR produced a significant arrhythmic response in exercised and
      sedentary rats as determined by all arrhythmia scoring systems. Four arrhythmia
      metrics resulted in significant differences between exercised and sedentary
      treatments (P < 0.001), whereas three metrics did not. CONCLUSIONS: Continuous
      versus discontinuous treatment of the data may account for variation in scoring
      system outcomes. These data confirm that exercise protects against IR-induced
      arrhythmias, and care must be taken when selecting an arrhythmia scoring system
      for ECG evaluation.

PMID- 21857373
TI  - Exercise protects cardiac mitochondria against ischemia-reperfusion injury.
AB  - PURPOSE: Three to five consecutive days of endurance exercise can protect the
      heart against an ischemia-reperfusion (IR) insult. However, the mechanisms
      responsible for this exercise-mediated cardioprotection remain unknown. Given the
      important role that mitochondria play in IR-induced cardiac myocyte injury, we
      hypothesized that exercise training promotes cardioprotection, at least in part,
      by increasing mitochondrial antioxidants, preventing mitochondrial release of
      reactive oxygen species, and protecting cardiac mitochondria against IR-induced
      oxidative damage and functional impairment. METHODS: To test our hypothesis,
      Sprague-Dawley rats were assigned to either sedentary (n = 16) or exercise
      trained (n = 16) groups. Exercise-trained animals performed 5 d of treadmill
      running for 60 min.d(-1) at 30 m.s(-1). Hearts were excised from sedentary and
      exercised-trained animals and were either perfused for 80 min or exposed to 40
      min of global ischemia followed by 45 min of reperfusion by using an ex vivo
      isolated working heart model. After the protocol, cardiac subsarcolemmal and
      intermyofibrillar mitochondria were isolated and used to determine respiratory
      control ratio, reactive oxygen species emission, and indices of oxidative stress
      and apoptosis. RESULTS: Our results support our hypothesis because exercise
      training protected both cardiac subsarcolemmal and intermyofibrillar mitochondria
      from IR-induced uncoupling and oxidative damage. Specifically, the levels of
      cardiac mitochondrial 4-hydroxynonenal-conjugated proteins were elevated in
      hearts from sedentary animals exposed to IR compared with cardiac mitochondria
      isolated from exercise-trained animals. Exercise also resulted in an increase in
      mitochondrial antioxidant enzymes (copper-zinc superoxide dismutase, manganese
      superoxide dismutase, and glutathione peroxidase) and prevented the IR-induced
      release of proapoptotic proteins from the mitochondria. CONCLUSIONS:
      Collectively, these novel findings reveal that exercise-induced cardioprotection
      is mediated, at least in part, through mitochondrial adaptations resulting in a
      mitochondrial phenotype that resists IR-induced damage.

PMID- 21857374
TI  - Rhabdomyolysis in the US Active Duty Army, 2004-2006.
AB  - PURPOSE: Rhabdomyolysis (RM) is a skeletal muscle disorder resulting in severe
      cellular injury caused by vigorous physical activity and other systemic
      etiologies. RM is associated with significant morbidity, such as acute renal
      failure, and can be fatal. RM that occurs in the US Active Duty Army (ADA)
      results in time lost from training, deployment, and combat. We sought to
      systemically describe the epidemiology of ADA clinical RM by quantifying RM in
      terms of absolute numbers, examine rate trends, and identify soldiers at elevated
      risk. METHODS: We used data from the Total Army Injury and Health Outcomes
      Database to calculate yearly RM rates in the overall ADA, as well as adjusted RM
      rates within soldier subpopulations for 2003-2006. RESULTS: During this period,
      the absolute numbers of clinically diagnosed ADA RM ranged between 382 and 419
      cases per year. Annual rates were 7-8 per 10,000, which is 300%-400% higher than
      the estimated US civilian population (2 per 10,000). In soldiers with a history
      of a prior heat injury, RM rates climbed to 52-86 per 10,000, a 7- to 11-fold
      increase. Increased RM rates were seen in soldiers who are male, African
      American, younger, less educated, and with a shorter length of service.
      Approximately 8% of yearly ADA RM cases resulted in acute renal failure, an
      estimate lower than that for the US civilian population. CONCLUSIONS: Our
      findings suggest that rates of RM are higher in the ADA than in the US civilian
      population. Rates remained fairly stable; however, relative to other ADA
      soldiers, those with prior heat injury, who are African American, or who have a
      length of service of less than 90 d are at the highest risk for RM development.

PMID- 21857375
TI  - Farnesol decreases biofilms of Staphylococcus epidermidis and exhibits synergy
      with nafcillin and vancomycin.
AB  - Biofilm infections are frequently caused by Staphylococcus epidermidis, are
      resistant to antimicrobial agents, and adversely affect patient outcomes. We
      evaluated farnesol (FSL), the Candida quorum-sensing molecule, on S. epidermidis
      biofilms, in vitro and in vivo. We evaluated ED50, ED75, and ED90 (drug
      concentrations causing 50%, 75%, and 90% inhibition, respectively) of FSL and
      evaluated synergy with nafcillin and vancomycin. FSL's effects on morphology of
      S. epidermidis biofilms were analyzed using confocal microscopy and real-time
      changes using a bioluminescent strain of S. epidermidis, Xen 43. In mice, effects
      of FSL treatment on s.c. catheter biofilms; cultures of blood, kidney, and
      catheter and pericatheter tissues; and bioluminescence in strain Xen 43 were
      evaluated. FSL inhibited biofilms (ED50 ranged from 0.625 to 2.5 mM) and was
      synergistic with nafcillin and vancomycin at most combination ratios. FSL
      significantly decreased biovolume, substratum coverage, and mean thickness of S.
      epidermidis biofilms. In mice, FSL significantly decreased viable colony counts
      of S. epidermidis from blood, kidney, and catheter and pericatheter tissues and
      decreased Xen 43 bioluminescence. We confirmed the antibiofilm effects of FSL
      both in vitro and in vivo, in a bioluminescent strain and its synergy with
      antibiotics. FSL may be effective against clinical S. epidermidis biofilm
      infections.

PMID- 21857376
TI  - Fiber tracking at term displays gender differences regarding cognitive and motor
      outcome at 2 years of age in preterm infants.
AB  - White matter microstructural changes can be detected with diffusion tensor
      imaging. It was hypothesized that diffusion parameters in the posterior limb of
      the internal capsule (PLIC) and corpus callosum (CC) bundles in preterm infants
      at term equivalent age (TEA) were associated with neurodevelopment at 2 y
      corrected age. In 67 preterm infants, fiber tracking was performed at TEA for the
      CC and both PLIC bundles. Volume, length, fractional anisotropy (FA), mean
      diffusivity, axial diffusivity, and radial diffusivity were determined for the
      three bundles. These parameters were assessed in relation to outcome on the
      Bayley Scales of Infant and Toddler Development III. In girls, volume and length
      of the CC bundle and right PLIC bundle volume were associated with cognition. In
      boys, volume, FA, mean and radial diffusivity, and length of the left PLIC were
      associated with fine motor scores. Correction for GA, birth weight,
      intraventricular hemorrhage, white matter injury, and maternal education did not
      change the results. Fiber tracking parameters in the PLIC and CC bundles in
      preterm infants at TEA revealed different associations with neurodevelopment
      between boys and girls. This study suggested that fiber tracking is a useful
      method to predict neurodevelopment in preterm infants.

PMID- 21857377
TI  - Changes in epigenetic regulation of CD4+ T lymphocytesin biliary atresia.
AB  - Biliary atresia (BA) is a virus-induced autoimmune disease associated with
      abnormal DNA methylation patterns that contribute to disease presentation. This
      study examined DNA methylation patterns, changes to genes associated with
      methylation regulation, and changes to the autoimmune-related gene interferon
      gamma (IFN-gamma) in CD4+ T cells from BA patients. We demonstrated that genomic
      DNA isolated from CD4+ T cells harvested from infants presenting with BA were
      hypomethylated relative to healthy controls. In addition, DNA methyltransferase
      (DNMT1) and DNMT3a mRNA levels were significantly lower in BA CD4+ T cells
      compared with controls and methyl-DNA-binding domain proteins (MBD1) mRNA
      expression (but not MBD4 detected at higher levels in BA patients), which was
      significantly lower in CD4+ T cells from BA infants than in controls. DNMT1
      expression positively correlated with global DNA methylation in BA CD4+ T cells.
      IFN-gamma mRNA expression levels in BA patients were also significantly
      increased, and the IFN-gamma gene promoter region was hypomethylated in BA CD4+ T
      cells compared with controls and negatively correlated with DNA methylation.
      These data suggest that methylation changes in CD4+ cells may contribute to BA
      disease presentation and progression by affecting the expression of genes
      associated with autoimmunity.

PMID- 21857378
TI  - Functional impairments at school age of children with necrotizing enterocolitis
      or spontaneous intestinal perforation.
AB  - We aimed to determine motor, cognitive, and behavioral outcome at school age of
      children who had either necrotizing enterocolitis (NEC) or spontaneous intestinal
      perforation (SIP). This case-control study included infants with NEC Bell's stage
      IIA onward, infants with SIP, and matched controls (1996-2002). At school age, we
      assessed motor skills, intelligence, visual perception, visuomotor integration,
      verbal memory, attention, behavior, and executive functions. Of 93 infants with
      NEC or SIP, 28 (30%) died. We included 52 of 65 survivors for follow-up. At mean
      age of 9 y, we found that 68% of the children had borderline or abnormal scores
      on the Movement Assessment Battery for Children (versus 45% of controls). Their
      mean total intelligence quotient (IQ) was 86 +/- 14 compared with 97 +/- 9 in the
      controls. In addition, attention and visual perception were affected (p < 0.01
      and p = 0.02). In comparison to controls, surgically treated children were at
      highest risk for adverse outcome. In conclusion, at school age, the motor
      functions and intelligence of many children with NEC or SIP were borderline or
      abnormal and, specifically, attention and visual perception were impaired.
      Children with NEC or SIP form a specific risk group for functional impairments at
      school age even though the majority does not have overt brain pathology.

PMID- 21857379
TI  - Oral administration of docosahexaenoic acid/eicosapentaeinoic acids is not
      anticonvulsant in rats: implications for translational research.
AB  - Omega-3 and omega-6 poly-unsaturated fatty acids (PUFAs) are dietary fatty acids
      that are involved in a myriad of physiological processes in the brain. Although
      experimental data have shown that PUFAs have anticonvulsant properties, the
      outcomes of clinical trials have been controversial. Docosahexaenoic acid (DHA)
      is a PUFA which has been reported to exert anticonvulsant effects. Here we
      studied anticonvulsant potential of a mixture of enriched n-3 PUFA upon their
      oral administration in rats. We did not observe an anticonvulsant effect of n-3
      PUFA in the i.v. pentylentetrazol threshold test. n-3 PUFA component was
      increased in the plasma of rats treated with the eicosapentaenoic acid (EPA)/DHA
      mix (275 mg/kg/d/400 mg/kg/d) due to the increase of both DHA and EPA. We also
      found modification of PUFA composition in the brain. Despite PUFA profiles
      modified both in plasma and in the brain, we did not find any anticonvulsant
      effect of orally administered DHA. Further studies are needed to define the type
      and the amount of fatty acids that would possess anticonvulsant properties. As
      the existing literature suggests that the route of administration of PUFA may be
      crucial, future studies should involve oral administration to provide relevant
      clinical information.

PMID- 21857380
TI  - Peripheral blood immune response elicited by beta-lactoglobulin in childhood
      cow's milk allergy.
AB  - Several studies analyzing the immune responses in patients with cow's milk
      allergy (CMA) have used T-cell lines or T-cell clones that require prolonged in
      vitro cell culturing and may result in a switched cell phenotype and function. We
      investigated immune responses to beta-lactoglobulin (b-LG) in peripheral blood
      mononuclear cells after a short in vitro antigen stimulation in children with
      acute CMA (both IgE-mediated and non-IgE-mediated forms) and in those who outgrew
      an IgE-mediated CMA. Healthy controls were also investigated. Peripheral blood
      mononuclear cells were assayed for IL-13, IFN-gamma, IL-4, and IL-10. Although b
      LG induced a cytokine production and/or cell proliferation almost in all
      children, included healthy controls, differences were observed among the four
      groups. Children with IgE-mediated CMA had a marked Th2-response, with high IL-13
      production and proliferation, but low IFN-gamma; by contrast, children with non
      IgE-mediated CMA produced no, or very low, IL-13 and cell proliferation.
      Children, who outgrew CMA, showed a shift to a Th1-response, with reduced IL-13
      and increased IFN-gamma. IL-10-responses were high in all groups, with the
      highest level in healthy children; by contrast, IL-4 was undetectable in all
      children. This study highlights the use of shortly stimulated peripheral blood
      cells to investigate the food-induced immune responses.

PMID- 21857381
TI  - Granulocyte-colony stimulating factor alleviates perinatal hypoxia-induced
      decreases in hippocampal synaptic efficacy and neurogenesis in the neonatal rat
      brain.
AB  - Using various animal models, studies have greatly expanded our understanding of
      perinatal hypoxia-induced neuronal injury in the newborn at the
      cellular/molecular levels. However, the synapse-basis pathogenesis and
      therapeutic strategy for such detrimental alterations in the neonatal brain
      remain to be addressed. We investigated whether the damaged synaptic efficacy and
      neurogenesis within hippocampal CA1 region (an essential integration area for
      mammalian learning and memory) of the neonatal rat brain after perinatal hypoxia
      were restored by granulocyte-colony stimulating factor (G-CSF) therapy. Ten-day
      old (P10) rat pups were subjected to experimentally perinatal hypoxia. G-CSF (10,
      30, or 50 MUg/kg, single injection/d, P11-16) was s.c. administered to neonatal
      rats which were analyzed on P17. Perinatal hypoxia reduced the expression in pRaf
      pERK1/2-pCREB(Ser-133) signaling, the synaptic complex of postsynaptic density
      protein-95 (PSD-95) with N-methyl-D-aspartate receptor (NMDAR) subunits (NR1,
      NR2A, and NR2B), synaptic efficacy, and neurogenesis. A representatively
      effective dosage of G-CSF (30 MUg/kg) alleviated the perinatal hypoxia-induced
      detrimental changes and improved the performance in long-term cognitive function.
      In summary, our results suggest a novel concept that synaptic efficacy defects
      exist in the neonatal brain previously exposed to perinatal hypoxia and that G
      CSF could be a clinical potential for the synapse-basis recovery in the perinatal
      hypoxia suffers.

PMID- 21857382
TI  - Candidate genes and risk for CP: a population-based study.
AB  - Studies suggest that genetic polymorphisms may increase an individual's
      susceptibility to CP. Most findings have yet to be corroborated in an independent
      cohort. This case-control study is nested within all 334,333 infants >=36 wk
      gestation born at Kaiser Permanente Medical Care Program, 1991-2002. We included
      only non-Hispanic whites who had a neonatal blood sample available. Case patients
      (n = 138) were identified from medical records to have spastic or dyskinetic CP.
      Controls (n = 165) were randomly selected from the population. We genotyped
      polymorphisms previously associated with CP: inducible NOS (iNOS)-231,
      apolipoprotein E (apoE) epsilon2 and epsilon4 alleles, TNF-alpha-308, IL-8 -251,
      lymphotoxin 60, endothelial NOS -922, endothelial protein C receptor 219, mannose
      binding lectin 54 and 52, factor V Leiden, methyltetrahydrofolate reductase 1298
      and 667, prothrombin 20210, and platelet activator inhibitor 11053. Similar to
      previous reports, the iNOS-231 T allele (25.7 versus 18.9%, p = 0.04) and the
      apoE epsilon4 allele (19.3 versus 13.2%, p = 0.04) were more common in patients
      with CP than in controls. However, there was no statistically significant
      association between any genetic polymorphism and CP after correction for multiple
      comparisons.

PMID- 21857383
TI  - Combined treatment strategies for unconjugated hyperbilirubinemia in Gunn rats.
AB  - We recently demonstrated that acceleration of the gastrointestinal transit by
      polyethylene glycol (PEG) treats unconjugated hyperbilirubinemia in jaundiced
      Gunn rats. It is unclear whether acceleration of gastrointestinal transit also
      (partly) underlies the therapeutic effects of established hypobilirubinemic
      treatments or whether PEG cotreatment might enhance these effects. We treated
      Gunn rats with phototherapy (17 MUW/cm2/nm), orlistat (200 mg/kg chow),
      ursodeoxycholate (5 g/kg chow), or calcium phosphate (CaP) (20 g/kg chow) either
      as single treatment or in combination with PEG. Three weeks of phototherapy,
      orlistat, ursodeoxycholic acid, or CaP treatment decreased plasma unconjugated
      bilirubin (UCB) levels by 47, 27, 28, and 45%, respectively (each p < 0.001),
      without a significant impact on gastrointestinal transit time. PEG cotreatment
      accelerated the gastrointestinal transit in all treatment groups, which resulted
      in an additive hypobilirubinemic effect of -20% and -26% (final plasma UCB -67
      and -53%, respectively) in phototherapy- and orlistat-treated animals. PEG
      cotreatment did not enhance the hypobilirubinemic effect of ursodeoxycholic acid
      or CaP. We conclude that phototherapy, orlistat, ursodoxycholic acid, and CaP do
      not exert their hypobilirubinemic effect via acceleration of the gastrointestinal
      transit. PEG cotreatment enhanced the hypobilirubinemic effects of phototherapy
      and of orlistat treatment. Current results support a clinical trial to evaluate
      PEG cotreatment during phototherapy.

PMID- 21857384
TI  - Slow salivary secretory IgA maturation may relate to low microbial pressure and
      allergic symptoms in sensitized children.
AB  - It is unknown why allergic symptoms do not develop in all sensitized children. We
      analyzed prospectively the postnatal secretory IgA (SIgA) development and whether
      high SIgA levels would protect sensitized infants from developing allergic
      symptoms. Salivary total IgA and SIgA levels were determined by ELISA, and
      allergy development was investigated at 3, 6, and 12 mo and at 2 and 5 y in two
      birth cohorts in Estonia (n = 110) and Sweden (n = 91), two geographically
      adjacent countries with different living conditions and allergy incidence. Total
      and SIgA levels increased with age, reaching adult levels at the age of 5.
      Virtually, all salivary IgA in Estonian children was in the secretory form, while
      a major part of IgA in Swedish saliva lacked the secretory component up to 2 y of
      age. In Sweden, high levels of salivary IgA without secretory component
      correlated inversely with house dust endotoxin levels. High SIgA levels were
      associated with less development of allergic symptoms in sensitized Swedish
      children. In conclusion, postnatal maturation of the salivary SIgA system
      proceeds markedly slower in Swedish than Estonian children, possibly as a
      consequence of low microbial pressure. SIgA may limit allergy-mediated tissue
      damage at mucosal surfaces in sensitized individuals.

PMID- 21857385
TI  - Successful treatment of severe cardiomyopathy in glycogen storage disease type
      III With D,L-3-hydroxybutyrate, ketogenic and high-protein diet.
AB  - Glycogen storage disease type III (GSD III) due to debranching enzyme deficiency
      presenting usually with hepatomegaly and hypoglycemia may be responsible for
      severe cardiomyopathy which is often fatal. Current treatment of GSD III is based
      on frequent high-carbohydrate meals that have no effect on the cardiomyopathy. We
      describe a 2-mo-old infant presenting with a familial form of GSD III complicated
      with cardiomyopathy. As conventional treatment was unable to improve his sister's
      cardiomyopathy who was deceased at age 11 mo, we proposed an experimental
      treatment combining the use of synthetic ketone bodies (D,L-3-OH butyrate) as an
      alternative energy source, 2:1 ketogenic diet to reduce glucose intake and high
      protein diet to enhance gluconeogenesis. Twenty-four months after the onset of
      this treatment, echocardiography showed an improvement of cardiomyopathy. Growth
      and liver size remained normal, and no side effects were observed. Blood glucose
      levels remained within the normal range and insulin levels decreased. These
      findings show that synthetic ketone bodies as well as low-carbohydrate, high
      lipid, and high-protein diet may be a more beneficial therapeutic choice
      therapeutic choice for GSD III patients with cardiomyopathy. These encouraging
      data need to be confirmed in more GSD III patients presenting with cardiac or
      muscular symptoms.

PMID- 21857386
TI  - Leptin in maternal serum and breast milk: association with infants' body weight
      gain in a longitudinal study over 6 months of lactation.
AB  - The adipokine leptin has been detected in human breast milk, but its effect on
      postnatal growth and development remains largely unclear. We hypothesized that
      leptin could affect infant's body weight gain during early lactation in the first
      6 mo of life. Therefore, we evaluated leptin levels in maternal serum and breast
      milk of 23 healthy, lactating mothers and their neonates in a prospective,
      longitudinal study. Leptin concentration was quantified by a commercially
      available human leptin RIA. Our results showed that leptin levels in breast milk
      were 22-fold lower than in maternal serum, but both parameters were positively
      correlated to each other (r = 0.431, p = 0.001) and to maternal BMI (serum: r =
      0.512, p < 0.001; milk: r = 0.298, p < 0.001) over 6 mo of lactation. A negative
      association was found between breast milk leptin levels during the first week
      after delivery and the infant weight gain from the end of the first to the sixth
      month (r = -0.681, p = 0.007). This suggests that milk-borne leptin provides a
      link between maternal body composition and infant growth and development and
      plays a critical role in regulating appetite and food intake during early
      infancy.

PMID- 21857387
TI  - Amino acid metabolism in the human fetus at term: leucine, valine, and methionine
      kinetics.
AB  - Human fetal metabolism is largely unexplored. Understanding how a healthy fetus
      achieves its fast growth rates could eventually play a pivotal role in improving
      future nutritional strategies for premature infants. To quantify specific fetal
      amino acid kinetics, eight healthy pregnant women received before elective
      cesarean section at term, continuous stable isotope infusions of the essential
      amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical
      blood was collected after birth and analyzed for enrichments and concentrations
      using mass spectrometry techniques. Fetuses showed considerable leucine, valine,
      and methionine uptake and high turnover rates. alpha-Ketoisocaproate, but not
      alpha-ketoisovalerate (the leucine and valine ketoacids, respectively), was
      transported at net rate from the fetus to the placenta. Especially, leucine and
      valine data suggested high oxidation rates, up to half of net uptake. This was
      supported by relatively low alpha-ketoisocaproate reamination rates to leucine.
      Our data suggest high protein breakdown and synthesis rates, comparable with, or
      even slightly higher than in premature infants. The relatively large uptakes of
      total leucine and valine carbon also suggest high fetal oxidation rates of these
      essential branched chain amino acids.

PMID- 21857388
TI  - Impaired neuromotor outcome in school-age children with congenital hypothyroidism
      receiving early high-dose substitution treatment.
AB  - Congenital hypothyroidism (CH) can lead to intellectual deficits despite early
      high-dose treatment. Our study aimed to determine whether motor impairments can
      occur despite early high-dose treatment. Sixty-three children with CH and early
      (median age of onset of treatment 9 d), high-dose treatment (median starting dose
      of levothyroxine 14.7 MUg/kg/d) were tested with the Zurich Neuromotor Assessment
      (ZNA) at a median age of 13.8 y (range 7.0-14.2 y). Median z-scores in the
      children with CH were -0.95 in the pure and -0.56 in the adaptive fine motor
      component, significantly lower than in the ZNA test norms (p < 0.001 and p =
      0.01, respectively). The 26 children with athyreosis were more affected than the
      33 children with dysgenesis, particularly in the pure motor (-1.55 versus -0.76,
      p = 0.03), adaptive fine motor (-1.31 versus 0.13, p < 0.01), and static balance
      task (-0.47 versus 0.67, p = 0.01). Boys performed worse than girls. Older age at
      onset of treatment was related to poorer adaptive fine motor performance.
      Movement quality (assessed by associated movements) was not affected. We conclude
      that severe CH can cause neuromotor deficits persisting into adolescence. These
      deficits cannot completely be reversed by postnatal treatment, but earlier age at
      treatment may reduce the degree of impairment.

PMID- 21857389
TI  - Characterization of neural breathing pattern in spontaneously breathing preterm
      infants.
AB  - The aim was to characterize the neural breathing pattern in nonintubated preterm
      infants. The diaphragm electrical activity (EAdi) and heart rate were
      simultaneously measured repeatedly for 1 h over several days using a modified
      feeding tube equipped with miniaturized sensors. The EAdi waveform was quantified
      for phasic and tonic activity, neural timings, and prevalence of recurring
      patterns, including central apnea. Ten infants with mean age 7 d (range, 3-13 d)
      were studied. Their birth weight was 1512 g (1158-1800 g) and GA at birth 31 wk
      (28-36 wk). Neural inspiratory and expiratory times were 278 ms (195-450 ms) and
      867 ms (668-1436 ms) and correlated with GA (p < 0.001). Tonic EAdi represented
      29.5% of phasic EAdi (16-40%) and was related to GA (r = 0.61, p < 0.001). For
      the group, 68% of the time was regular phasic breathing (without tonic activity)
      and 29% of the time with elevated tonic activity. Central apneas >5 s occurred on
      average 10 times per hour (2-29). Heart rate reductions were correlated to
      central apnea duration. In conclusion, esophageal recordings of the EAdi waveform
      demonstrate that neural breathing pattern is variable, with regards to timing,
      amplitude, and pattern with a distinct amount of tonic diaphragm activity.

PMID- 21857390
TI  - Effects of iron supplementation on auditory brainstem response in marginally LBW
      infants.
AB  - LBW infants are at risk of iron deficiency (ID), which is associated with
      impaired nervous system development and may lead to prolonged auditory brainstem
      response (ABR) latencies. We hypothesized that iron supplementation shortens ABR
      latencies in marginally LBW (MLBW, 2000-2500 g) infants. In a randomized,
      controlled trial, 285 healthy MLBW infants received 0, 1, or 2 mg iron/kg/d of
      iron supplements from 6 wk to 6 mo of age. ABR absolute wave V latencies and
      central conduction time (CCT) were measured at the endpoint. There were no
      significant differences between groups in ABR wave V latencies (n = 218).
      Furthermore, there were no significantly prolonged ABR latencies in infants with
      ID (n = 32). CCT was significantly higher in the 2 mg group than in the placebo
      group (n = 126). However, there were no significant correlations between CCT and
      iron intake or any iron status variable, suggesting that differences in CCT were
      not caused by iron. We conclude that iron supplements did not improve ABR
      latencies, and iron-deficient MLBW infants did not have impaired ABR latencies at
      6 mo, suggesting that ABR is not a sensitive measure of impaired neurological
      development or that mild/moderate ID causes no such impairment in MLBW infants.

PMID- 21857391
TI  - Levels of breast milk PBDEs from southern Taiwan and their potential impact on
      neurodevelopment.
AB  - In vivo studies have demonstrated that prenatal or neonatal exposure to
      polybrominated diphenyl ethers (PBDEs) causes developmental neurotoxicity.
      However, there is a lack of human data. Our hypothesis was that PBDEs would
      result in lower infant neurodevelopment scores. This is a post hoc analysis of
      previous studies. Fourteen PBDEs in 70 breast milk were analyzed using a high
      resolution gas chromatograph/high-resolution mass spectrometer. Infant
      neurodevelopment at the age of 8-12 mo was determined using the Bayley Scales of
      Infants and Toddlers Development, third edition (Bayley-III). The median of
      Sigma14 PBDEs (the sum of 14 PBDE congeners) was 2.92 ng/g lipid. The Sigma14
      PBDE concentrations were not correlated with Bayley-III scores on cognitive,
      language, motor, social-emotional, or adaptive behavior scales. A significantly
      inverse association between brominated diphenyl ether (BDE)-209 and the cognitive
      scale was found after multivariate stepwise linear regression analyses (B = 
      0.007, adjusted R = -0.224, p = 0.032). In contrast, the language scale was
      positively correlated with BDE-196 (B = 0.096, adjusted R = 0.315, p = 0.002).
      Our results are consistent with most in vivo studies, suggesting that prenatal or
      postnatal exposure to BDE-209 potentially delays the neurological development.

PMID- 21857392
TI  - Macular buckling for myopic macular hole retinal detachment: a new approach.
AB  - PURPOSE: To evaluate the efficacy and safety of a new technique of macular
      buckling in the treatment of myopic macular hole retinal detachment. METHODS:
      Twenty-six consecutive cases of myopic macular hole retinal detachment were
      included in the study. For 20 cases, the macular buckling was the primary
      procedure. The other six cases were recurrent after vitrectomy and silicone oil
      tamponade. The technique is described in detail. RESULTS: Retinal attachment
      occurred in all cases with improvement of vision. The postoperative vision ranged
      from counting fingers to 6/36 depending on the degree of atrophy of the retinal
      pigment epithelium in the background. Only one case developed submacular
      hemorrhage with deterioration of vision to counting fingers close to the eye.
      Other complications were recorded. CONCLUSION: The described technique is
      remarkably accurate and does not require any specially designed implants. It is
      highly recommended for cases of myopic macular hole retinal detachment with
      atrophic background and deep posterior staphyloma and for recurrent cases after
      vitrectomy with or without silicone oil.

PMID- 21857393
TI  - Transition from film to digital fundus photography in the Longitudinal Studies of
      the Ocular Complications of AIDS.
AB  - PURPOSE: To describe the transition to digital imaging and assess any impact on
      ocular disease classification. METHODS: Film and digital images, acquired by
      certified photographers, were evaluated independently according to standard
      procedures for the following: image quality, presence of cytomegalovirus
      retinitis lesions, and their extent and proximity from disk and macula.
      Intergrader agreement within the digital medium was also assessed. RESULTS: Among
      the 15 eyes with cytomegalovirus retinitis, the mean difference between film and
      digital images for linear distance of lesion edge to disk was 0.02 disk
      diameters, for distance to center of macula was -0.04 disk diameters, and area
      covered by cytomegalovirus retinitis was 0.95 disk area. There was no
      statistically significant difference in distance and area measurements between
      media. Intergrader agreement in measurements of digital images was excellent for
      distance and area estimated. CONCLUSION: Our results suggest that digital grading
      of cytomegalovirus retinitis in Longitudinal Studies of the Ocular Complications
      of AIDS is comparable with that from film regarding disease classification,
      measurements, and reproducibility. These findings provide support for continuity
      of grading data, despite the necessary transition in imaging media.

PMID- 21857394
TI  - Construction of artificial laminae of the vertebral arch using bone marrow
      mesenchymal stem cells transplanted in collagen sponge.
AB  - STUDY DESIGN: A rabbit laminectomy model was used to evaluate the efficacy of
      artificial laminae of vertebral arch using bone marrow-derived osteoblasts
      transplanted in a collagen sponge. OBJECTIVE: The objective of this study is to
      reconstruct the artificial laminae of vertebral arch using bone marrow-derived
      osteoblasts transplanted in a collagen sponge on a rabbit model. SUMMARY OF
      BACKGROUND DATA: Because the laminectomy and semilaminectomy can effectively
      decompress the spinal cord and expand the vertebral canal, they have been
      performed as routine surgical procedures. However, long-term follow-up results
      show that these procedures can lead to many serious complications. A variety of
      strategies have been used to solve these complications, but there are few
      experiments to determine the efficacy of reconstructing the laminae of vertebral
      arch using bone marrow-derived osteoblasts and the collagen sponge. METHODS: The
      bone marrow mesenchymal stem cells (BMSCs) from the bone marrow in the femur of 2
      week-old rabbits were obtained by centrifugation and adhesion. The BMSCs were
      induced to differentiate into osteoblasts, which were transplanted into collagen
      sponge to construct the tissue-engineering bone. A total of 48 rabbits were
      randomly divided into three groups. Lumbar laminectomies were performed on all of
      the rabbits. Group A was the control. Groups B and C were implanted with collagen
      sponge and tissue-engineering bone, respectively. The artificial laminae of the
      vertebral arch were examined qualitatively by imageology and histomorphometry.
      RESULTS: The artificial laminae of the vertebral arch successfully formed 4 weeks
      after the operation in group C; computed tomography examination at 4 weeks showed
      that the new laminae of vertebral arch were formed, and that the vertebral canal
      was intact. CONCLUSION: The artificial laminae of the vertebral arch can be
      successfully constructed using tissue engineering of transplanted BMSCs.

PMID- 21857395
TI  - Clinical outcome of lumbar total disc replacement using ProDisc-L in degenerative
      disc disease: minimum 5-year follow-up results at a single institute.
AB  - STUDY DESIGN: A retrospective clinical data analysis. OBJECTIVE: To determine the
      therapeutic effectiveness of lumbar total disc replacement (TDR) using ProDisc-L
      (Synthes Spine, West Chester, PA) in the patients with degenerative disc diseases
      (DDD) with a minimum follow-up of 5 years. SUMMARY OF BACKGROUND DATA: Early
      successful clinical results of lumbar TDR have been reported. However, few
      reports have published its therapeutic effectiveness in the long term. METHODS:
      The patients were examined preoperatively and at 3 months, 1 year, 2 years, and
      more than 5 years postoperatively, and assessed using visual analog scale (VAS),
      Oswestry disability index (ODI), physical health component summary (PCS) of the
      36-Item Short Form Health Survey questionnaire, and sporting activity scale
      scores. At last follow-up visits, two additional questions were asked:
      satisfaction with surgery and willingness to undergo the same treatment. Finally,
      clinical success was assessed using the Food and Drug Administration definition.
      RESULTS: Thirty-five patients were included in the study. The mean follow-up
      period was 72 months (6 years). Postoperatively, all outcome measure scores (VAS,
      mean ODI, PCS, and sports activity scores) immediately improved and these
      improvements were maintained at last follow-up visits with statistical
      significance. However, outcome score improvements were observed to be slightly,
      though significantly, lower at last follow-up visits than at 1 or 2 years
      postoperatively. Eighty-eight percent of patients were "satisfied" or "somewhat
      satisfied" with treatment and 60% were prepared to undergo the same treatment
      again. Twenty-five patients (71.4%) achieved clinical success. CONCLUSION: This
      study reveals that lumbar TDR using ProDisc-L is a safe and effective treatment
      for chronic back pain caused by lumbar DDD as assessed at more than 5 years
      postoperatively. Nevertheless, outcome scores were slightly, though significantly
      lower at last follow-up visits than at 1 and 2 years postoperatively. A longer
      term follow-up study is warranted.

PMID- 21857396
TI  - Multifocal osteolytic lesions within lumbar spine in a middle-aged Chinese woman:
      a benign metastasizing leiomyoma?
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a case presented as osteolytic
      lesions involving 2 inconsecutive lumbar, which was pathologically proved to be
      of smooth muscular origin. SUMMARY OF BACKGROUND DATA: Smooth muscle tumor of
      uncertain malignant potential (STUMP) could be diagnosed when the neoplasm showed
      some malignant behavior, whereas its histologic image revealed very low
      malignance. A 47-year-old woman presented with low back pain and numbness of the
      left lower extremity attributable to osteolytic lesions in the second and fourth
      lumbar vertebral bodies, which was subsequently diagnosed as STUMP. A benign
      metastasizing leiomyoma was highly suspected. METHODS: Clinical, pathologic, and
      radiologic characters of the patient with STUMP confined within the lumbar spine
      were retrospectively reviewed. A mini review was also conducted. RESULTS: We
      describe the first spine-confined case of STUMP. CONCLUSION: Significant new
      information in the growing literature of this rare and newly identified diagnosis
      has addressed the need for orthopedists to consider the STUMP diagnosis.

PMID- 21857397
TI  - The path to capacity: resilience and spinal chronic pain.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVE: To analyze the relationship
      between resilience, acceptance, coping, and adjustment to spinal chronic pain.
      SUMMARY OF BACKGROUND DATA: Several studies have concluded that resilience is
      relevant in predicting pain and physical functioning among patients with chronic
      pain. Although resilience may have a role in preventing or living with chronic
      pain, there is little research on the effects of resilience on adjustment among
      patients with chronic pain. METHODS: Multivariate multiple regression by
      structural equation modeling was performed to simultaneously determine the
      influence of all the predictor variables on all the dependent variables. The
      sample was composed of 299 patients (138 men and 161 women) suffering from
      chronic spinal pain. : Higher levels of resilience were associated with higher
      levels of pain acceptance and active coping strategies. Active coping and
      acceptance were associated with higher levels of adjustment to pain. CONCLUSION:
      Positive personality characteristics could play a crucial role in patient
      adjustment, and thus clinicians should take into account the positive path to
      capacity to better understand the chronic pain experience.

PMID- 21857398
TI  - Internal stabilization of a flexion-distraction injury of the upper cervical
      spine of a toddler: a new technique and literature review.
AB  - STUDY DESIGN: A case report and literature review. OBJECTIVE: To present a new
      and simple technique of fixation without fusion of a rare unstable Salter-Harris
      type I injury in the upper cervical spine of a 23-month-old toddler. SUMMARY OF
      BACKGROUND DATA: Surgical treatment of unstable pediatric cervical spine injuries
      most commonly involves posterior fusion with internal fixation, usually posterior
      wiring. METHODS: Detailed description of the surgical procedure carried out for
      fixating an unstable flexion-distraction injury in a 23-month-old toddler, with
      severe head injury and pneumothorax, is presented. RESULTS: A rare unstable
      flexion-distraction injury in the upper cervical spine of a toddler was
      successfully treated with a posterior Number 2 Vicryl (polyglactin 910; ETHICON
      Division of Johnson & Johnson) suture fixation, with good healing of the
      ligaments and end plates, without fusion. Preservation of motion was achieved
      without obvious instability at 28 months postsurgery. CONCLUSION: In selected
      cases of cervical spine injuries in the young pediatric population, simple
      stabilization of the spine using degradable Number 2 Vicryl (polyglactin 910)
      sutures with minimal exposure can provide sufficient stability until healing
      occurs. Advantages are that fusion is avoided and motion preserved.

PMID- 21857399
TI  - Estimating risk of pulmonary neoplastic embolism during vertebroplasty.
AB  - STUDY DESIGN: Vertebroplasty was simulated on a pig model. OBJECTIVE: To evaluate
      the risk of neoplastic tissue migration into lungs during vertebroplasty. SUMMARY
      OF BACKGROUND DATA: The application of vertebroplasty in spinal metastasis is not
      well documented. The risk of neoplastic tissue migration into the lungs during
      vertebroplasty remains unknown. METHODS: A cancer model was built in 11 Landrace
      pigs (50 kg) by injecting 99mTc-labeled albumin macroaggregates into the center
      of L5 and L6 prior to vertebroplasty. Continuous scintigraphic imaging was
      performed with 1-minute frames over the lungs and vertebrae before and after
      injection to ensure steady state and baseline. We surveyed free TcO4- in thyroid.
      Twenty minutes after the 99mTc injection, 2-level vertebroplasty was performed at
      L5 and L6 with 3 Jamshidi needles in each vertebra. Into each vertebra, on
      average, 2.8 +/- 1.1 mL of poly(methyl methacrylate) cement (Depuy CMW,
      Blackpool, UK) was injected. Quantitative scintigrams were obtained within 90
      minutes after vertebroplasty. X-rays and quantitative computed tomography scans
      quantified cement distribution. Means of 99mTc activity before and after
      vertebroplasty were compared in a paired t test. RESULTS: In this cancer model,
      we found an 80% risk of tissue migration to the lungs when performing
      vertebroplasty. In average, the study showed a significant amount of
      macroaggregate migration of 1.87% total range from 0% to 8% (CI: 0.05%-0.37%)
      with P = 0.045. There was no free TcO4- in the thyroid. Despite the standardized
      procedure, we found a large interindividual variation of pulmonary embolism.
      CONCLUSION: It is demonstrated that there exists a significant risk of exporting
      neoplastic disease or fatty tissue to the lungs when performing vertebroplasty. A
      similar adverse effect can be expected with balloon kyphoplasty. In patients with
      metastatic disease, vertebroplasty should be limited to those with short life
      expectancy.

PMID- 21857400
TI  - What is the role of "nonorganic somatic components" in functional capacity
      evaluations in patients with chronic nonspecific low back pain undergoing fitness
      for work evaluation?
AB  - STUDY DESIGN: Analytical cross-sectional study. OBJECTIVE: To assess the
      association of "nonorganic somatic components" together with physical and other
      psychosocial factors on functional capacity evaluation (FCE) in patients with
      chronic nonspecific low back pain (NSLBP) undergoing fitness-for-work evaluation.
      SUMMARY OF BACKGROUND DATA: Functional capacity evaluation is increasingly used
      for physical fitness-for-work evaluation in patients with chronic NSLBP, but
      results seem to be influenced by physical as well as psychosocial factors. The
      influence of nonorganic somatic components together with physical and other
      psychosocial factors on FCE performance has not yet been investigated. METHODS:
      One hundred twenty-six patients with chronic NSLBP referred for physical fitness
      for-work evaluation were included. The 4 FCE tests were lifting from floor to
      waist, forward bend standing, grip strength, and 6-minute walking. Nonorganic
      somatic components were assessed with the 8 nonorganic somatic signs as defined
      by Waddell and were adjusted for age, sex, days off work, salary in the previous
      occupation, pain intensity, fear avoidance belief, and perceived functional
      ability in multivariate regression analyses. RESULTS: Between 42% and 58% of the
      variation in the FCE tests was explained in the final multivariate regression
      models. Nonorganic somatic components were consistent independent predictors for
      all tests. Their influence was most important on forward bend standing and
      walking distance, and less on grip strength and lifting performance. The physical
      factors of age and/or sex were strongly associated with grip strength and
      lifting, less with walking distance, and not at all with forward bend standing.
      The influence of at least 1 other psychosocial factor was observed in all FCE
      tests, having the highest proportion in the 6-minute walking test. CONCLUSION:
      Nonorganic somatic components seem to be consistent independent predictors in FCE
      testing and should be considered for interpretation of test results.

PMID- 21857401
TI  - Comparison of computed tomography myelography and radioisotope cisternography to
      detect cerebrospinal fluid leakage in spontaneous intracranial hypotension.
AB  - STUDY DESIGN: A retrospective observational study. OBJECTIVE: To compare the
      usefulness of radioisotope cisternography (RIC) and computed tomography
      myelography (CTM) for the detection of cerebrospinal fluid (CSF) leakage in
      spontaneous intracranial hypotension (SIH). SUMMARY OF BACKGROUND DATA: CSF
      leakage sites have been generally identified by RIC in patients with SIH.
      Although a number of reports have recently indicated the usefulness of CTM,
      whether RIC or CTM more reliably detects leakage sites has not been decided
      because the 2 tests have not been directly compared. METHODS: Both RIC and CTM
      were performed, and the findings were compared in 12 patients with SIH strictly
      meeting the second edition of the International Classification of Headache
      Disorders diagnostic criteria. : On RIC, the detection rate of leakage including
      indirect signs, an early vesicular radioisotope (RI) accumulation and delayed
      ascent of the RI to the cerebral convexity, was observed in 100%, but that of the
      direct sign, paraspinal RI accumulation, was in 8 patients (67%). On CTM, the
      epidural collection of intraspinally administered contrast medium was
      demonstrated in all patients (100%), and the collection site was located in the
      cervical and thoracic vertebral regions in most cases. When RIC and CTM findings
      were collated, paraspinal accumulation in the cervical and thoracic regions on
      RIC corresponded to the entire or a part of the findings on CTM. In contrast, in
      4 of 5 patients with paraspinal accumulation in the lumbosacral region, epidural
      collection was not noted in this region on CTM. CONCLUSION: In patients with SIH,
      epidural collection on CTM may more accurately demonstrate CSF leakage compared
      with paraspinal RI accumulation on RIC.

PMID- 21857402
TI  - The efficacies of 2 ceramic bone graft extenders for promoting spinal fusion in a
      rabbit bone paucity model.
AB  - STUDY DESIGN: Prospective, randomized, controlled animal study. OBJECTIVE: To
      determine the efficacies of 2 ceramic composite bone graft extenders for
      promoting spinal fusion. SUMMARY OF BACKGROUND DATA: Although autogenous bone is
      still considered the "gold standard" graft material for fusion procedures, its
      use is associated with a number of limitations. Synthetic ceramic composites
      represent a class of osteoconductive materials that may be employed as
      supplements or even alternatives to autograft. In this study, we compared the
      fusion rates generated by 2 ceramic composite bone graft extenders (MasterGraft
      and Mozaik Strips) with that obtained with autograft in a rabbit bone paucity
      model. METHODS: Thirty-two New Zealand white rabbits undergoing noninstrumented
      posterolateral lumbar fusion were randomized to 1 of the following 4 groups: 100%
      autograft, 50% autograft, 50% autograft with Mozaik Strip, and 50% autograft with
      MasterGraft Strip. The rabbits were followed postoperatively for 8 weeks at which
      time the spinal segments were explanted and assessed for the presence of a solid
      fusion. RESULTS: The arthrodesis rates by manual palpation of the 100% and 50%
      autograft controls were 75% (6 of 8 animals) and 12.5% (1 of 8), respectively (P
      < 0.01). In the 50% autograft/Mozaik and 50% autograft/MasterGraft groups, 3/8
      and 1/8 of the rabbits were determined to have fused successfully, respectively
      (P = 0.569). However, there were no significant differences between the fusion
      rate of the 50% autograft cohort and those exhibited by the Mozaik or MasterGraft
      animals (P = 0.569 and 1.00, respectively). CONCLUSION: This study provides
      further evidence that the quantity of autograft may influence the process of
      spinal fusion such that the arthrodesis rate was significantly lower when less
      bone was implanted. Neither of the ceramic composite scaffolds seemed to enhance
      the fusion response compared to an equivalent amount of autograft alone,
      suggesting that these substances may need to be combined with other osteogenic
      materials to optimize bone production.

PMID- 21857403
TI  - Intradural extramedullary hemangiopericytoma of the thoracic spine infiltrating a
      nerve root: a case report and literature review.
AB  - STUDY DESIGN: Review the presentation and diagnosis of an intradural
      extramedullary hemangiopericytoma of the thoracic spine. OBJECTIVE: To present a
      rare case of intradural, subpial hemangiopericytoma in the thoracic spine, with a
      brief overview of the literature. SUMMARY OF BACKGROUND DATA: Spinal intradural
      extramedullary hemangiopericytoma is rare entity that radiographically mimics
      nerve-sheath tumors. These lesions are typically diagnosed at surgery performed
      due to suspicion of tumor. METHODS: A 20-year-old man who presented with back
      pain, leg weakness, and sphincter incontinence. MR imaging demonstrated an
      intradural extramedullary lesion at the T9-T10 level that was isointense on T1-
      and T2-weighted images and homogeneously enhancing after administration of
      gadolinium, with cystic components seen on T2-weighted images. The preoperative
      diagnosis was meningioma or schwannoma. RESULTS: At surgery, the lesion was
      bluish and completely subpial, with apparent nerve root invasion. Pathological
      examination revealed a neoplasm adjacent to a nerve root with possible focal
      infiltration. Abundant reticulin fibers and widened, branching vascular channels
      imparting a staghorn appearance were seen. Up to five mitotic figures were
      counted in one high-power field. On immunostaining, the neoplastic cells were
      diffusely immunoreactive for CD99 and immunonegative for EMA, CD34, and S-100
      protein. The pathological diagnosis was consistent with anaplastic
      hemangiopericytoma, WHO grade III. CONCLUSION: This is the ninth report of spinal
      intradural hemangiopericytoma. The location of the neoplasm supports the
      hypothesis that hemangiopericytoma may arise from the spinal pial capillaries.

PMID- 21857404
TI  - Spinal cord intramedullary pressure in thoracic kyphotic deformity: a cadaveric
      study.
AB  - STUDY DESIGN: In vitro cadaveric study of thoracic spinal cord intramedullary
      pressure (IMP) in kyphotic deformity. OBJECTIVE: To define the relationship
      between thoracic spinal kyphotic deformity and spinal cord IMP. SUMMARY OF
      BACKGROUND DATA: Previous studies of asymptomatic volunteers have revealed that
      there is wide variation in regional sagittal neutral upright thoracic spinal
      alignment with "normal" thoracic T4-T12 kyphosis ranging up to approximately +69
      degrees  for 98.5% of the asymptomatic adult population. We sought to determine
      whether IMP changes in response to increasing thoracic kyphosis. METHODS: In 8
      fresh-frozen cadavers, a progressive kyphotic deformity was created. Cadavers
      were positioned sitting with physiological thoracic kyphosis, head stabilized
      using a skull clamp, and spine segmentally instrumented from occiput to L2. The
      T3-T4 ligamentum flavum was removed, dura opened, and 3 pressure sensors were
      advanced caudally to T4-T5, T7-T8, and T11-T12 within the cord parenchyma. A
      stepwise thoracic kyphotic deformity was then induced by sequentially releasing
      and retightening the skull clamp while distracting posterior short segment rods
      and closing anterior segmental osteotomies. After each step, fluoroscopic images
      and pressure measurements were obtained; the T4-T12 Cobb angle was measured.
      RESULTS: Minor IMP increases of 2 to 5 mm Hg were observed at 1 or more spinal
      cord levels in 1 of 8 cadavers when the Cobb angle was less than +51 degrees  and
      in 4 of 8 cadavers when the angle was more than +51 degrees  and less than +63
      degrees . For Cobb angles more than +51 degrees  and less than +63 degrees , a
      statistically significant, minor increase in IMP was detected at the T7-T8 level
      only (P = 0.02). At Cobb angles exceeding +63 degrees , DeltaIMP progressively
      increased at 1 or more spinal cord levels in 8 of 8 cadavers. Cobb angles ranging
      from +63 degrees  to +149 degrees  resulted in statistically significant
      increases in IMP ranging to more than 50 mm Hg. DeltaIMP did not correlate with
      segmental spinal canal diameter (stenosis). CONCLUSION: Thoracic kyphosis less
      than +51 degrees  resulted in no meaningful increase in IMP, whereas kyphosis
      measuring +51 degrees  to +63 degrees  resulted in minor increases in IMP. After
      the thoracic kyphosis exceeded +63 degrees , IMP increased significantly.
      DeltaIMP with spinal alignment may help explain the wide range of "normal"
      thoracic neutral upright sagittal alignment in studies of asymptomatic adult
      individuals and may help further define thoracic kyphotic deformity.

PMID- 21857405
TI  - WITHDRAWN: Biomechanical Comparison of Lumbar Total Disc Arthroplasty, Discectomy
      and Fusion: Effect on Adjacent-Level Disc Pressure and Facet Joint Force.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 21857406
TI  - Cartilage intermediate layer protein (CILP) regulation in intervertebral discs.
      The effect of age, degeneration, and bone morphogenetic protein-2.
AB  - STUDY DESIGN: An in vitro study using rabbit intervertebral disc tissue and disc
      cells. OBJECTIVE: To evaluate the effects of disc degeneration, age, and bone
      morphogenetic proteins-2 (BMP-2) on cartilage intermediate layer protein (CILP)
      expression and elucidate the molecular mechanism by which BMP-2 regulates CILP
      expression. SUMMARY OF BACKGROUND DATA: CILP is implicated in several diseases
      that affect cartilage. The CILP polymorphism acts as a modulator of lumbar disc
      disease susceptibility. However, regulation of the CILP gene in disc tissue
      remains poorly understood. METHODS: Intact discs from young rabbits were
      punctured to induce disc degeneration. These young rabbits and other older
      rabbits were used to measure the expression of CILP, proteoglycan, and collagen
      II using Western blot and real-time PCR. Primary disc cells from the rabbits were
      treated with rhBMP-2, or siRNAs, and the gene expression was analyzed by Western
      blot and real-time PCR. The activity of the CILP promoter was measured by using
      the Dual Luciferase Reporter Assay System. RESULTS: Our study demonstrates that
      the intervertebral disc expresses significant levels of CILP and that the
      expression of CILP increases substantially with increasing age and disc
      degeneration. In contrast, the expression of proteoglycan and collagen II
      decrease with increasing age and disc degeneration. BMP-2 induces the expression
      of CILP protein and stimulates the activity of the CILP promoter in rabbit
      primary disc cells. The induction of CILP by BMP-2 can be augmented with age.
      Knockdown of Smad1 by siRNA abolishes the stimulatory effects of BMP-2 on CILP
      expression in the primary disc cells. CONCLUSION: Our data demonstrate that disc
      degeneration, age, and BMP-2 are regulators of the CILP gene. BMP-2 induces CILP
      expression by activating the Smad1 signal pathway.

PMID- 21857407
TI  - Risk factors for acute cervical spinal cord injury associated with ossification
      of the posterior longitudinal ligament.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To identify risk factors for
      traumatic cervical spinal cord injury (SCI) associated with ossification of the
      posterior longitudinal ligament (OPLL) by comparing patients with SCI and those
      with cervical myelopathy (CM) associated with OPLL. SUMMARY OF BACKGROUND DATA:
      Although the prevalence of OPLL among patients with cervical SCI is high, little
      is published about the risk factors for SCI associated with OPLL. METHODS: We
      evaluated 3 groups of patients: 34 with SCI associated with OPLL, 32 with CM
      associated with OPLL, and 32 normal controls. Developmental canal diameter,
      spinal canal stenosis, type of OPLL, and presence of ossification of the anterior
      longitudinal ligament (OALL) were evaluated using 3-dimensional computed
      tomography. RESULTS: The mean age of the SCI group was 71.5 years, significantly
      more than that of the CM group (63.3 years). The SCI and CM groups had
      significantly smaller developmental canals than controls. Canal stenosis caused
      by OPLL was significantly more severe in the CM group than in the SCI group.
      There were no significant differences in sex distribution or the type of OPLL.
      Mixed or segmental types of OPLL were the main cause of SCI and CM. The SCI group
      showed a significantly higher incidence of OALL (56%) than the CM group (22%).
      Cervical SCI occurred at the edge of the OPLL or OALL in 20 patients (59%). If
      limited to mixed or continuous types of OPLL, 18 of the 19 patients (95%)
      sustained SCI at the edge of the OPLL or OALL. CONCLUSION: Risk factors for
      cervical SCI associated with OPLL were being elderly, having a mixed or segmental
      type of OPLL, and presence of OALL. Most instances of SCI occurred at edges of
      the OPLL or OALL. Severe spinal canal stenosis caused by OPLL was not an
      essential risk factor for developing SCI.

PMID- 21857408
TI  - Maintaining neutral sagittal cervical alignment after football helmet removal
      during emergency spine injury management.
AB  - STUDY DESIGN: Descriptive laboratory study. OBJECTIVE: To determine whether the
      placement of padding beneath the occiput after helmet removal is an effective
      intervention to maintain neutral sagittal cervical spine alignment in a position
      comparable with the helmeted condition. SUMMARY OF BACKGROUND DATA: Current on
      field recommendations for managing football athletes with suspected cervical
      spine injuries call for face mask removal, rather than helmet removal, because
      the combination of helmet and shoulder pads has been shown to maintain neutral
      cervical alignment. Therefore, in cases when helmet removal is required,
      recommendations also call for shoulder pad removal. Because removal of equipment
      causes motion, any technique that postpones the need to remove the shoulder pads
      would reduce prehospital motion. METHODS: Four lateral radiographs of 20 male
      participants were obtained (age = 23.6 +/- 2.7 years). Radiographs of
      participants wearing shoulder pads and helmet were first obtained. The helmet was
      removed and radiographs of participants with occipital padding were obtained
      immediately and 20 minutes later and finally without occipital padding. Cobb
      angle measurements for C2-C6 vertebral segments were determined by an orthopedic
      spine surgeon blinded to the study's purpose. Intraobserver reliability was
      determined using intraclass coefficient analysis. Measurements were analyzed
      using a 1*4 repeated-measures analysis of variance and post hoc pairwise
      comparisons with Bonferroni correction. RESULTS: Intraobserver analysis showed
      excellent reliability (intraclass correlation = 1.0; 95% confidence interval
      [CI], 0.999-1.0). Repeated-measures analysis of variance detected significant
      differences (F(3,17) = 13.34; P < 0.001). Pairwise comparisons revealed no
      differences in cervical alignment (all measurements reported reflect lordosis)
      when comparing the baseline helmeted condition (10.1 degrees  +/- 8.7 degrees ;
      95% CI, 6.0-14.1) with the padded conditions. Measurements taken after removal of
      occipital padding (14.4 degrees  +/- 8.1 degrees ; 95% CI, 10.6-18.2)
      demonstrated a significant increase in cervical lordosis compared with the
      immediate padded measurement (9.5 degrees  +/- 6.9 degrees ; 95% CI, 6.3-12.7; P
      = 0.011) and the 20-minute padded measurement (6.5 degrees  +/- 6.8 degrees ; 95%
      CI, 3.4-9.7; P < 0.001). CONCLUSION: Although face mask removal remains the
      standard, if it becomes necessary to remove the football helmet in the field,
      occipital padding (along with full body/head immobilization techniques) may be
      used to limit cervical lordosis, allowing safe delay of shoulder pad removal.

PMID- 21857409
TI  - Biomechanical analysis of sacral screw strain and range of motion in long
      posterior spinal fixation constructs: effects of lumbosacral fixation strategies
      in reducing sacral screw strains.
AB  - STUDY DESIGN: A cadaveric biomechanical experiment was conducted to assess the
      range of motion (ROM) and screw strain at S1 in a long instrumented spinal fusion
      construct to compare the effects of various surgical strategies for L5-S1
      stabilization. OBJECTIVE: To directly quantify and compare S1 screw strains and
      lumbosacral ROM for 4 different L2-S1 posterior segmental instrumented fusion
      constructs: an L2-S1 pedicle screw (PS) construct alone and PS with each of 3
      different augmentations, anterior lumbar intebody fusion (ALIF), anterior axial
      interbody threaded rod (AxiaLITR), or iliac screws. SUMMARY OF BACKGROUND DATA:
      Iliac screws and anterior interbody devices are commonly used as augmentation to
      reduce the incidence of S1 screw loosening in long fusion constructs.
      Alternatives, such as AxiaLITR, may provide similar biomechanical advantages
      without many of the same long-term limitations and morbidities. METHODS: Pure
      moment flexibility testing was performed in 6 cadaveric lumbosacral spines.
      Specimens were tested with 4 instrumentation constructs: (1) PS L2-S1, (2) PS
      with ALIF, (3) PS with AxiaLITR, and (4) PS with iliac screws. Bilateral S1 PS
      were instrumented with strain gauges, directly measuring screw loading while
      simultaneously measuring L5-S1 ROM with a noncontact camera system. RESULTS:
      Average S1 screw strains were the greatest with the PS group and were reduced by
      38% with the ALIF group, 75% with the AxiaLITR group, and 78% with the iliac
      screw group in flexion-extension (P < 0.05). Similar trends were observed in
      torsion (P < 0.05). Strains in lateral bending were smaller in magnitude and were
      similar among all 4 constructs. The AxiaLITR and iliac screw groups demonstrated
      a similar ROM and significant reduction in ROM at L5-S1 compared with both the PS
      and ALIF groups (P <= 0.02 and P < 0.03). CONCLUSION: The results of this study
      indicated that iliac screws and AxiaLITR provide similar stability at L5-S1,
      while significantly reducing the strain on the S1 screws.

PMID- 21857410
TI  - Alterations in T2 relaxation magnetic resonance imaging of the ovine
      intervertebral disc due to nonenzymatic glycation.
AB  - STUDY DESIGN: An in vitro study using ovine intervertebral discs to correlate the
      effects of increasing advanced glycation end-products (AGEs) with disc hydration
      evaluated by magnetic resonance imaging (MRI). OBJECTIVE: To determine the
      relationship between the level of AGEs and tissue water content in intervertebral
      discs using T2 relaxation MRI. SUMMARY OF BACKGROUND DATA: AGEs result from
      nonenzymatic glycation, and AGEs have been shown to accumulate in the
      intervertebral disc tissue with aging and degeneration. AGEs can alter
      biochemical properties, including the hydrophobicity of the extracellular matrix.
      Because one of the degenerative signs of the intervertebral disc (IVD) is reduced
      hydration, we hypothesized that increased levels of tissue AGEs contribute to
      disc hydration. T2 relaxation MRI has been shown to be sensitive to the hydration
      status of the disc and may be valuable in detecting the changes in the IVD
      mediated by the increase of AGEs. METHODS: Thirty-eight IVDs were obtained from 4
      ovine spines, and the annulus fibrosis (AF) and nucleus pulposus (NP) tissues
      were isolated from these discs. The tissues were incubated in either a
      ribosylation or control solution for up to 8 days to induce the formation of
      AGEs. T2 relaxation times were obtained from these tissues after ribosylation.
      These tissues were subsequently analyzed for hydration, proteoglycan, collagen,
      and AGEs content. RESULTS: In vitro ribosylation led to the increased
      accumulation of AGEs and reduced water content in both the AF and NP in a dose
      dependent manner, but did not affect the proteoglycan and collagen composition.
      When analyzed by MRI, ribosylation significantly altered the mean T2 relaxation
      times in the NP (P = 0.001), but not in the AF (P = 0.912). Furthermore, the mean
      T2 values in the NP significantly decreased with increasing periods of incubation
      time (P < 0.001). CONCLUSION: This study demonstrates that levels of AGEs in the
      IVD may affect the tissue water content. Moreover, these ribosylation-mediated
      changes in tissue hydration were detectable using T2 relaxation MRI. T2
      relaxation MRI may provide a noninvasive tool to measure in vivo changes in disc
      hydration that are negatively correlated with the accumulation of AGEs.

PMID- 21857412
TI  - Incarceration of the radial head associated with a radial head fracture,
      radiocapitellar dislocation, and proximal radioulnar translocation.

PMID- 21857413
TI  - Perioperative lateral trochanteric hip fractures: sliding hip screw versus
      percutaneous compression plate for intertrochanteric hip fractures.

PMID- 21857415
TI  - Percutaneous plating of the distal tibia and fibula: risk of injury to the
      saphenous and superficial peroneal nerves.

PMID- 21857416
TI  - Hang them high: a hands-free technique for limb-holding during surgical
      preparation.

PMID- 21857419
TI  - OTA highlight paper predicting future displacement of nonoperatively managed
      lateral compression sacral fractures: can it be done?
AB  - PURPOSE: This study was designed to assess the rate of displacement in
      nondisplaced sacral fractures and to determine if certain fracture patterns are
      more prone to future displacement. DESIGN: Retrospective. SETTING: Two Level I
      trauma centers. PATIENTS: Patients consisted of those sustaining a lateral
      compression pelvic fracture whose age was 17 years or older, had less than 5 mm
      of initial sacral displacement, were the result of a high-energy mechanism, and
      had radiographs documenting bony union. INTERVENTION: By protocol, patients
      meeting these criteria were mobilized and maintenance of alignment was documented
      by serial radiographs. RESULTS: All fractures were classified according to the
      Orthopaedic Trauma Association classification system, the Young and Burgess
      mechanistic classification system, and to the location of the sacral fracture as
      described by Denis. In addition, sacral fractures were classified as complete or
      incomplete. Additionally, the number and location of rami fractures were
      recorded. Of the initial 117 fractures, 23 were determined to displace and
      largely consisted of a single fracture pattern. Fractures consisting of a
      complete sacral fracture combined with bilateral rami fractures displaced at a
      rate of 68% (15 of 22). In contrast, incomplete sacral fractures with an
      ipsilateral rami injury had no displaced unions. CONCLUSION: Incomplete lateral
      compression sacral fractures that are associated with ipsilateral rami fractures
      can be treated nonoperatively and are unlikely to displace. In contrast, those
      with a complete sacral fracture and bilateral rami fractures displace at a
      significantly greater rate.

PMID- 21857420
TI  - Invited commentary.

PMID- 21857421
TI  - Examination under anesthetic for occult pelvic ring instability.
AB  - OBJECTIVE: To describe the technique and results of stress examination with
      fluoroscopy under anesthesia (EUA) to determine stability and the need for
      operative stabilization of traumatic pelvic ring injuries. DESIGN: Retrospective
      chart and radiographic review. SETTING: Level I trauma center. SUBJECTS:
      Skeletally mature patients with traumatic incomplete posterior pelvic ring
      injuries. METHODS: Patients were consented for EUA if preoperative radiographs
      and computed tomographic scanning of the pelvis demonstrated an incomplete injury
      to the posterior pelvic ring (Orthopaedic Trauma Association [OTA] 61-B type
      injuries). Patients with nondisplaced anterior compression fractures of the
      sacral ala without internal rotation or a fracture line exiting the posterior
      cortex were excluded from this analysis. Similarly, skeletally immature patients
      or those with complete instability of the pelvic ring (OTA 61-C type injuries)
      were excluded. All patients meeting inclusion criteria were taken to the
      operating room, anesthetized, and placed in the supine position for stress
      examination (EUA) of the pelvic ring using intraoperative dynamic fluoroscopy.
      Examination consisted of a resting static film followed by internal rotation,
      external rotation, and push-pull maneuvers of both lower extremities. Each of
      these maneuvers was performed using the anteroposterior, inlet, and outlet
      projections, providing a total of 15 distinct images for each patient's
      examination. The preoperative classification of the pelvic ring injury was then
      accepted or redefined based on the amount of rotational and translational
      instability in the axial, coronal, and sagittal planes. The decision to proceed
      with anterior and/or posterior operative reduction and stabilization was
      subsequently based on the degree of pelvic ring instability noted during the EUA.
      RESULTS: A total of sixty-eight patients underwent an EUA of their pelvis by the
      senior author. Fifty males and 18 females with an average age of 35 years
      comprised the study group. In all, 37 anteroposterior compression (APC or OTA 61
      B1) injuries and 31 lateral compression (LC or OTA 61-B2) injuries were
      evaluated. Of the 14 pelvic ring injuries initially classified as an APC-1, seven
      (50%) were deemed stable and treated nonsurgically, whereas seven (50%) were felt
      to have sufficient instability (an occult APC-2) to warrant treatment with
      anterior fixation based on EUA. Of the 23 injuries initially classified as an APC
      2, all but one required surgical fixation: 13 (57%) were treated with anterior
      fixation alone (APC-2a), whereas nine (39%) were treated with anterior fixation
      and supplemental iliosacral screw placement (APC-2b) based on the degree of
      instability noted during the EUA. Of the 20 injuries initially classified as an
      LC-1, 13 (65%) were stable and treated nonsurgically (LC-1a), whereas seven (35%)
      were treated with anterior and/or posterior stabilization (LC-1b) based on the
      degree of instability noted during the EUA. CONCLUSIONS: The reported incidence
      of poor functional outcomes associated with pelvic fracture may be attributable,
      in part, to inadequate treatment of misdiagnosed injuries and chronic instability
      and/or malunion. Performing an examination under anesthesia with dynamic stress
      fluoroscopy as described in this series revealed occult instability in 50% of
      presumed APC-1 injuries, 39% of APC-2 injuries, and 37% of LC-1 injuries. We
      propose a modification to the Young-Burgess Classification system to reflect the
      dynamic component of pelvic ring instability disclosed on EUA as follows: APC-2a
      for those injuries requiring anterior only fixation, APC-2b for those injuries
      that may require treatment with anterior and posterior fixation, LC-1a for those
      injuries that are stable and do not require internal fixation, and LC-1b for
      those lateral compression injuries that may require treatment with internal
      fixation. We conclude that pelvic EUA merits further analysis as an important
      diagnostic tool that may provide additional information regarding instability of
      the pelvic ring.

PMID- 21857422
TI  - Invited commentary.

PMID- 21857423
TI  - Quality of radiographic reduction and perioperative complications for transverse
      acetabular fractures treated by the Kocher-Langenbeck approach: prone versus
      lateral position.
AB  - OBJECTIVE: To compare radiographic reduction, intraoperative factors, and
      perioperative complications for transversely oriented acetabular fractures
      treated by the Kocher-Langenbeck approach with the patient in either the prone or
      lateral position. DESIGN: Retrospective study. SETTING: Two regional referral
      trauma centers. PARTICIPANTS: Sixty-six skeletally mature individuals with
      transversely oriented acetabular fractures treated operatively through the Kocher
      Langenbeck approach in either the prone or lateral position. INTERVENTION:
      Operative fixation of an acute transverse acetabular fracture through the Kocher
      Langenbeck approach. MAIN OUTCOME MEASURES: This study primarily assessed the
      radiographic reduction of two similar consecutive cohorts of patients surgically
      treated for transversely oriented acetabular fractures using the Kocher
      Langenbeck approach with the patient positioned in either the lateral or prone
      position. Secondary outcome measures included operative time, estimated blood
      loss, and perioperative complications. RESULTS: Thirty-three transversely
      oriented acetabular fractures were reduced and stabilized with the patient in the
      lateral position, whereas 33 fractures were treated with the patient in the prone
      position. Demographic and injury variables as well as surgical time and estimated
      blood loss were similar between the two groups. Two postoperative infections
      occurred in each group, and one incomplete iatrogenic sciatic nerve palsy was
      recognized in the lateral group. The mean maximum fracture residual displacement
      measured on postoperative radiographs was 2.1 mm (range, 0-7 mm) in the lateral
      group compared with 1.3 mm (range, 0-7 mm) in the prone group (P = 0.08). The
      quality of reduction according to Matta's criteria was graded in prone positioned
      patients as anatomic in 20 patients (61%), imperfect in 11 patients (33%), and
      poor in two patients (6%), whereas lateral-positioned patients were graded as
      anatomic in 14 patients (42%), imperfect in 13 patients (40%), and poor in six
      (18%) patients (P = 0.21). DISCUSSION AND CONCLUSION: This study demonstrated a
      trend toward higher radiographic residual fracture displacement in patients with
      transversely oriented acetabular fractures reduced and stabilized through the
      Kocher-Langenbeck approach in the lateral position compared with those positioned
      prone. However, no significant differences were observed in operative time,
      estimated blood loss, or perioperative complications between the two groups.

PMID- 21857424
TI  - Use of femoral shaft fracture classification for predicting the risk of
      associated injuries.
AB  - OBJECTIVES: To investigate the hypothesis that specific fracture patterns in
      patients with femoral shaft fractures can predict the likelihood of associated
      injuries. DESIGN: Retrospective cohort study. SETTING: Level I trauma center.
      PATIENTS/PARTICIPANTS: Consecutive patients treated because of a traumatic
      diaphyseal femoral fracture. MAIN OUTCOME MEASUREMENT: We studied the association
      between the Orthopaedic Trauma Association (OTA) fracture classification (derived
      from initial radiographs) and concomitant injuries of the head, spine, chest,
      abdomen, and pelvis with a severity of two or more points according to the
      Abbreviated Injury Scale by logistic regression analysis. RESULTS: One hundred
      forty-three of 203 patients (80 men, 63 women; mean age 54 +/- 26 years) met the
      inclusion criteria. All patients had unilateral diaphyseal fractures, 64 OTA 32.A
      (45%), 46 OTA 32.B (32%), and 33 OTA 32.C (23%). In addition, 134 associated
      injuries were identified in 52 patients. Increasing fracture severity, as
      expressed by the OTA classification (ie, A, B, C), was significantly associated
      with a higher likelihood of thoracic (odds ratio [OR], 5.89; 95% confidence
      interval [CI], 2.59-13.40), pelvic (OR, 4.55; 95% CI, 2.01-10.28), upper (OR,
      2.38; 95% CI, 1.27-4.48), and lower extremity injuries (OR, 3.12; 95% CI, 1.78
      5.46). Fracture severity explained between 70% and 86% of the probability of
      having accompanying injuries. CONCLUSION: Radiographic grading of the severity of
      a femoral shaft fracture may signal the presence of accompanying injuries and
      should contribute to the clinical decision-making process in severe trauma.

PMID- 21857425
TI  - Legg-Calve-Perthes disease centenary.

PMID- 21857426
TI  - A brief history of Legg-Calve-Perthes disease.
AB  - Legg-Calve-Perthes (LCP) disease has an extensive history that has provided an
      ongoing intellectual challenge for the orthopaedic community. Debate around
      etiology and treatment of LCP disease continues even after its initial
      description in the early 1900 s. In order for modern day clinicians to have a
      full understanding of the condition, one must be a scholar of its development.
      The purpose of our review will be to discuss the scientific communities'
      understanding of presentation, etiology, and treatment of LCP disease over time.

PMID- 21857427
TI  - Legg-Calve-Perthes disease at 100: a review of evidence-based treatment.
AB  - BACKGROUND: The year 2010 is the 100th anniversary of the publication of the
      first 3 reports describing Legg- Calve-Perthes disease (LCPD). This paper
      summarizes available evidence previously published and discussed at the several
      world conferences honoring the occasion. METHODS: Relevant articles with evidence
      based data regarding the efficacy of treatment methods for LCPD were reviewed by
      the author. RESULTS: The reviewed studies noted 3 factors related to outcome in
      patients treated for LCPD as follows: the age at onset, the classification of
      severity of femoral head involvement, and the type of treatment. In patients over
      age 8 at onset, surgical treatment with femoral varus osteotomy or Salter
      innominate osteotomy was associated with improved Stulberg outcomes compared with
      nonoperative treatment, in those who had lateral pillar B or B/C border class
      involvement. In the Wiig et al study, patients over age 6 with Catterall 3, 4
      classification had better outcomes with these surgical treatment methods compared
      with nonoperative methods. Children under age 6 at onset had a good prognosis
      except for a small number of patients between age 4 and 6 years with lateral
      pillar C involvement. CONCLUSIONS: There is valid evidence of an association
      between surgical treatment of certain patients with LCPD and improved
      radiographic outcome.

PMID- 21857428
TI  - Legg-Calve-Perthes disease: etiology, pathogenesis, and biology.
AB  - Legg-Calve-Perthes disease is a complex pediatric hip disorder with many
      uncertainties. Various theories on its etiology have been proposed but none have
      been validated conclusively. Through experimental studies, however, some insight
      into the pathogenesis of a femoral head deformity after ischemic necrosis has
      been gained. These studies reveal that mechanical and biological factors
      contribute to the development of the femoral head deformity. Better understanding
      of the pathobiology of Legg-Calve-Perthes disease will lead to the development of
      more effective treatments, which are able to specifically target the pathogenic
      processes.

PMID- 21857429
TI  - Prognosis and prognostic factors of Legg-Calve-Perthes disease.
AB  - This is an overall review of the published literature in the past 100 years on
      the prognosis and prognostic factors of Legg-Calve-Perthes disease (LCPD). There
      were considerable limitations and inadequacies of the reported series. LCPD is
      not a common disease, and thus most reports were based on relatively small series
      collected retrospectively over a long period of time without clearly defined case
      selection, assessment, treatment, follow-up period, and outcome measures. Few
      studies, if any, would satisfy the strict definition of prognosis, which should
      only mean those prognostic factors derived from observation of the natural
      history of the disease-that is the uninterrupted progressive development of a
      disease that runs its course from onset-inception to resolution without any
      intervention or treatment. This review attempted to summarize from the mixed
      series of studies the generally described demographic, clinical, and radiologic
      prognostic factors of LCPD. The most important radiologic prognostic signs
      include the extent of femoral capital epiphysis involvement, the degree of
      metaphyseal changes, and lateral subluxation of femoral head and depend
      significantly on the time of assessment after the onset of the disease. More
      detailed discussions on prognostication based on the structured classification
      systems that have evolved in the past few decades would be described.

PMID- 21857430
TI  - Natural history of early onset and late-onset Legg-Calve-Perthes disease.
AB  - Legg-Calve-Perthes disease develops after interruption of the blood supply to the
      capital femoral epiphysis. This results in various changes in the femoral
      epiphysis and metaphysis, the capital femoral epiphysis, growth plate, and the
      acetabulum. The necrotic bone of the epiphysis is gradually replaced by new bone,
      and over 2 to 4 years complete healing of the epiphysis occurs. The evolution of
      this process can be clearly seen on radiographs and the disease can be divided
      into distinct stages. In the early stages of the disease, the epiphysis may
      extrude outside the confines of the acetabulum and this predisposes to femoral
      head deformation. The propensity for femoral head extrusion is greater in the
      older child, and consequently the likelihood of femoral deformation is higher in
      children who are older.

PMID- 21857431
TI  - Arthrogram in Legg-Calve-Perthes disease.
AB  - There is a consensus among researchers that the treatment for Legg-Calve-Perthes
      disease, whether conservative or surgical, is always based on the concept of
      "containment," that is, maintaining the femoral head inside the acetabulum socket
      throughout the entire evolution of the disease. Thus, the size and shape of the
      proximal femoral epiphysis should be monitored during the evolution of the
      disease. Although diagnosis is carried out by conventional radiographies in many
      medical institutions, this examination does not give us this information.
      Therefore, it becomes necessary to resort to other examination techniques, such
      as pneumoarthrography and magnetic resonance imaging. In our institution, we
      noticed the importance of hip arthrography in Legg-Calve-Perthes disease from a
      study carried out by Laredo in 1985 that classified the disease into 5 groups
      based on the form and size of the femoral head and its position in the labrum.
      According to this researcher, group III, which he called "hip at premature
      arthrographic risk," requires action and yields the best results. The researchers
      have the opinion that dynamic pneumoarthrography is the best method for
      establishing an ideal position for the femoral head in relation to the acetabulum
      when surgical treatment is indicated.

PMID- 21857432
TI  - Magnetic resonance imaging in Legg-Calve-Perthes disease: review of literature.
AB  - Even after 100 years, problems of early evaluation, classification, and treatment
      of Legg-Calve-Perthes disease (LCPD) are still under discussion. In the past,
      most of the studies on the natural history of LCPD proved that majority of the
      cases heal spontaneously without functional impairment at maturity, but if we
      consider the late results a considerable number of hips become painful and
      require prosthesis. Thus, in this review the results of the several important
      papers published in the last 40 years and the articles about magnetic resonance
      imaging in LCPD are analyzed to evaluate whether there can be a new way to reach
      an early best diagnosis to improve the prognostic evaluation.

PMID- 21857433
TI  - Classification of Legg-Calve-Perthes disease.
AB  - Although the etiology of Perthes disease remains unknown 100 years after its
      first description, there are many articles that describe the disease course,
      final outcome, and results of treatment. A system of classification of the extent
      and severity of the disease is essential to understanding variability of Perthes,
      and along with the age of the patient when first affected, is useful in
      predicting long-term outcomes. Published reports of treatment strategies and
      their success depend on effective classification of the disease severity and
      radiographic result at final follow-up concerning head sphericity, congruency
      with the acetabulum, and arthritis. This article reviews published articles that
      contain classification systems and details presently used systems that are
      helpful in understanding and in treating Perthes.

PMID- 21857434
TI  - Nonsurgical treatment of Legg-Calve-Perthes disease.
AB  - It was first postulated in the case Legg-Calve-Perthes disease that nonweight
      bearing and prolonged immobilization were the most effective methods for
      prevention of the destructive changes in the hip joint. However, later
      developments adopted joint mobilization using ambulatory orthoses. The
      containment method altered the main concept of orthotic treatment, based on its
      better results than the conventional method. The surgical treatment also aims at
      a containment effect. The choice of either nonsurgical or surgical treatment is
      still difficult. It should be considered after comprehensively examining the
      patient in terms of the severity of disease, patient's and family's psychological
      outlook and the doctor's skill. Nonsurgical treatment will still be one of the
      options for selected patients.

PMID- 21857435
TI  - The role of bracing in Legg-Calve-Perthes disease.
AB  - BACKGROUND: Treatment methods in Legg-Calve-Perthes disease (LCPD) have varied
      during the 100-year history of this disorder. This is a review of the present
      practice of bracing in LCPD. METHODS: Published articles from the last 35 years
      were reviewed including primary analyses of bracing, meta-analysis, and summaries
      of present opinion. The recent literature was also evaluated to determine the
      present bracing practices. RESULTS: Studies performed regarding specific braces
      failed to show that they offer any advantage over other methods of management,
      including no treatment. Similarly, meta-analyses showed that hips treated with
      nonoperative containment had little difference in outcome based on present
      methods of analysis. Opinion papers suggested that the use of braces in LCPD
      should be significantly decreased or discontinued altogether. There is a major
      controversy regarding weaning and discontinuation of bracing. The use of Petrie
      casts can be considered in "salvage" techniques of hips with subluxation or
      hinged abduction. CONCLUSIONS: The present literature does not provide evidence
      sufficient to support the use of bracing in LCPD. On the basis of this review,
      our recommendation is that the abduction orthosis should rarely be used in the
      treatment of LCPD. Petrie casts still have a role in short-term treatment in
      patients with deformed femoral heads before complete reossification.

PMID- 21857436
TI  - Potential for bisphosphonate treatment in Legg-Calve-Perthes disease.
AB  - BACKGROUND: The observation that the pathogenesis of femoral head deformity in
      Legg-Calve-Perthes disease (LCPD) relates to bone resorption without subsequent
      coupled bone formation leads quickly to the hypothesis that antiresorptive agents
      may provide a useful adjunctive avenue for therapy. Robust bone catabolism in the
      absence of anabolism can only lead to femoral head deformity. METHODS: The
      published data on bisphosphonate use in models of LCPD was reviewed. RESULTS:
      Multiple animal studies support the further investigation of bisphosphonates and
      other anticatabolic agents in LCPD. Clinical data is only now starting to be
      gathered on the basis of animal and safety data.Rodent studies of traumatic and
      spontaneous osteonecrosis confirm that femoral head shape can be preserved by
      systemic bisphosphonate administration. Large animal piglet studies also show
      better preservation of the femoral head shape with systemic and local
      bisphosphonate administration, and also illustrate that systemic therapy requires
      initial revascularization of the necrotic head before its distribution within the
      head-a potential drawback of systemic therapy. Timing of effective dosing is
      likely to be very important. If the goal of treatment is to prevent deformity,
      then the window of therapy may be limited to an early stage of the disease before
      the significant collapse of the head.Although limiting bone resorption and
      preserving femoral head shape with bisphosphonates or other anticatabolic drugs
      may be of use, anabolic stimulation to speed up healing and new bone formation
      may also be desirable. Physical factors such as weight relief and activity
      modification may be important as the mechanical properties of the necrotic
      femoral head are significantly compromised during healing. The inflammatory
      nature of early LCPD is likely to also play a role in pathogenesis. These factors
      cannot be addressed by the use of antiosteoclastic therapy alone. CLINICAL
      RELEVANCE: Further basic science and clinical studies are required to clarify the
      role of bisphosphonates as adjunctive therapy in LCPD.

PMID- 21857437
TI  - Femoral varus osteotomy in Legg-Calve-Perthes disease.
AB  - In a preliminary report in 1965, Axer proposed femoral varus derotation osteotomy
      as an alternative method for treating Legg-Calve-Perthes disease. Thereafter,
      this became one of the most popular operative methods in the treatment of the
      disease. A literature analysis of this method experienced during the years is
      discussed and the investigator's personal approach is described.

PMID- 21857438
TI  - Salter osteotomy in Legg-Calve-Perthes disease.
AB  - BACKGROUND: Femoral head containment in Legg-Calve-Perthes disease (LCPD) can be
      either surgical or nonsurgical. The Salter or innominate osteotomy is a common
      method of surgical containment. This is a review of the technique and results of
      this osteotomy in LCPD. METHODS: The operative technique is relatively simple but
      requires considerable experience to perform correctly. It can be used alone or in
      combination with a proximal femoral varus osteotomy. The indications for a Salter
      osteotomy are essentially the same as in any form of containment treatment in
      LCPD. This includes: age at clinical onset of 6 to 10 years (perhaps, 5 y in
      female), more than one-half capital femoral epiphyseal involvement (Catterall
      groups III or IV, Salter-Thompson group B, and lateral pillar groups B, B/C, and
      C), and a good range of hip motion before surgery. The osteotomy alone is usually
      indicated for younger children with recent clinical onset and no femoral head
      deformity or subluxation. The combined procedure is better suited for older
      children and those with subluxation or a deformed femoral head. RESULTS:
      Currently, the results of treatment are best determined at skeletal maturity
      using the Stulberg et al classification. When used alone, approximately 90% to
      95% of the involved hips will have achieved a Stulberg et al class I, II, or III
      result. When combined with a proximal femoral varus osteotomy, the results are
      somewhat less because of the older age at onset and/or the presence of a deformed
      hip. CONCLUSIONS: The Salter osteotomy in LCPD is an effective method of surgical
      treatment that can alter the natural history of the disease process. The main
      advantage of this osteotomy is its effect on femoral head remodeling during
      remaining growth.

PMID- 21857439
TI  - Advanced containment methods for the treatment of Perthes disease: Salter plus
      varus osteotomy and triple pelvic osteotomy.
AB  - The goal of intervention in Legg-Calve-Perthes disease has been to prevent
      femoral head deformation by containing the head within the acetabulum, using it
      as a mold for guiding femoral head development. With appropriate proximal femoral
      morphology, premature arthritis can hopefully be avoided. Both nonsurgical and
      surgical methods of treatment have evolved over time, from abduction casts and
      braces to advanced surgical containment methods, which are now the mainstay of
      treatment. The purpose of this study is to briefly review the evolution of
      surgical treatment of Legg-Calve-Perthes disease, and to concentrate on 2
      advanced surgical containment methods: combined Salter innominate osteotomy with
      femoral varus osteotomy and triple pelvic osteotomy.

PMID- 21857440
TI  - Labral support shelf arthroplasty for containment in early stages of Legg-Calve
      Perthes disease.
AB  - BACKGROUND: Containment of the hip has become a popular strategy for treatment of
      severe Legg-Calve-Perthes disease; however, the best method remains unclear. This
      study describes a minimal-incision variation of the labral support shelf
      arthroplasty, which uses arthroscopic visualization and an allograft buttress on
      the shelf support. The outcome in a group of hips undergoing this minimal
      incision variation is compared by the Stulberg classification with a group
      treated by the traditional anterolateral open operative approach. In addition,
      the outcomes of both groups of labral support shelf arthroplasties are compared
      then with other containment techniques used in our hospital consisting of Petric
      cast, varus femoral osteotomy, and innominate osteotomy of Salter. METHODS: Forty
      two patients who fulfilled the following criteria underwent a labral support
      shelf arthroplasty: (1) unilateral hip disease; (2) age equal to or older than 6
      years at diagnosis; (3) Catterall group III or IV; and (4) Herring B or C
      disease. Twenty patients had a traditional open approach (group I) and 22 had an
      approach using a minimal-incision arthroscopic visualization and allograft
      buttress on the shelf support (group II). Outcomes by the Stulberg classification
      were then compared between these groups (I and II) and with 29 cases of Petri
      casting, 15 of varus femoral osteotomies, or 15 of innominate osteotomies of
      Salter. RESULTS: There is no statistical difference in Stulberg classification
      outcomes between group I and group II, which demonstrates that a minimally
      invasive technique is satisfactory and prevents substantial tissue dissection as
      is required in a standard anterior lateral approach to the hip, P>0.05. In
      addition, there is no statistical difference in Stulberg classification outcomes
      between the labral support shelf arthroplasties and common containment methods
      such as Petri casting, varus femoral osteotomies, or the innominate osteotomy of
      Salter, P>0.05. CONCLUSIONS: The labral support shelf arthroplasty by either the
      traditional method or the minimal-incision variation offers similar Waldenstrom
      class outcomes when compared with a Petric cast, a varus femoral osteotomy, or an
      innominate osteotomy of Salter. We believe the labral support shelf arthroplasty
      technique is simple to perform and does not induce a permanent deformity in the
      proximal femur or acetubulum.

PMID- 21857441
TI  - Core decompression and labral support for the treatment of juvenile
      osteonecrosis.
AB  - The final outcome of Legg-Calve-Perthes disease is variable and depends mostly on
      the age of the patient at onset and the amount of femoral head involvement. The
      goals of treatment are to achieve a round femoral head with a congruous hip joint
      and to contain the femoral head to avoid extrusion. We will term this condition
      in the adolescent age, "juvenile osteonecrosis," as we understand that the
      osteonecrosis pattern responds differently to that in younger patients who
      develop Perthes and it is similar to adult osteonecrosis. Most of the deformity
      comes from the collapse and enlargement in size of the femoral head. Therefore,
      the treatment rationale should be tailored to address these differences. We
      believe that early core decompression combined with containment in the form of a
      shelf acetabuloplasty can change the natural history of the disease based on both
      adolescent and adult literature. The core allows removal of the necrotic segment;
      it improves vascularization to the affected area and may provide structural
      support in some cases. The shelf provides support to distribute the forces across
      the joint and prevents lateral migration. It also provides better acetabular roof
      to prevent early dysplastic changes that lead to arthritis.

PMID- 21857442
TI  - The role of valgus osteotomy in LCPD.
AB  - When the hip is noncontainable due to established hinge abduction, restoration of
      joint congruity and/or acetabular volume should be the primary goal of treatment.
      Various salvage procedures have been attempted for the management of
      noncontainable hips, but no long-term follow-up data have been reported. A valgus
      osteotomy, which permits realignment of the leg with the hip in the "best fit"
      position in neutral weight-bearing position, has been most commonly applied to
      restore joint congruity and to reduce femoroacetabular impingement. Evidence
      continues to accumulate, indicating that valgus osteotomy, when combined with or
      without other salvage procedures, can result in sustained improvement of symptoms
      and function, and beneficially influences remodeling of the hip in a subgroup of
      children with hinge abduction.

PMID- 21857443
TI  - Transtrochanteric rotational osteotomy for late-onset Legg-Calve-Perthes disease.
AB  - BACKGROUND: The pathology of late-onset Legg-Calve-Perthes disease (LCPD) is
      similar to that of avascular necrosis of the femoral head in adult and is
      associated with poorer prognosis of the hip. The optimal treatment for this
      condition is still controversial. The purpose of this study was to evaluate the
      long-term clinical results of the transtrochanteric rotational osteotomy for the
      patients with LCPD onset at more than 9 years of age. METHODS: Individuals
      included 14 hips in 13 cases with the mean age at onset of the disease and
      operation of 10 years 9 months and 12 years. Average follow-up periods were 12
      years. All cases were resistant to the conservative treatments and did not have
      our indications for varus osteotomy. Clinical results were evaluated using Merle
      d'Aubigne Postel score and the modified Stulberg criteria. RESULTS: Average Merle
      d'Aubigne Postel score at the final follow-up was 16.2 points ranging from 12 to
      18 points. All patients did not have additional treatment except nail removal.
      Stulberg class II, III, and IV were obtained in 5, 2, and 7 hips, respectively.
      More spherical femoral head was obtained in patients with less head involvement
      and more bone preservation or new bone formation at posterior pillar. Three hips
      showed slight narrowing of joint space without severe osteoarthritic changes.
      CONCLUSIONS: Transtrochanteric rotational osteotomy is an effective procedure to
      salvage the hips of the late-onset LCPD. Amount of head involvement, posterior
      and lateral pillar had influences on the surgical outcomes.

PMID- 21857444
TI  - Arthrodiastasis of the hip.
AB  - BACKGROUND: Hip distraction in Legg-Calve-Perthes disease unloads the joint,
      which negates the harmful effect of the stresses on the articular surface, which
      may promote the sound healing of the areas of necrosis. METHODS: Nonarticulated
      arthrodiastasis without soft tissue release using an Ilizarov external fixator
      was applied to 29 patients with Legg-Calve-Perthes disease (older than 8 y at
      onset and lateral pillar type C or B). RESULTS: Follow-up period ranged from 2.5
      to 11 years with an average of 7.5 years. Twenty-seven cases (93%) had
      improvement of the range of motion postoperatively. Preoperatively, all patients
      had constant pain, whereas at last follow-up 26 (86%) patients had no pain and 3
      had an improvement. Stulberg classification was applied to 21 cases who reached
      skeletal maturity at last follow-up: 9 cases were type II, 7 cases were type III,
      4 cases were type IV, and 1 case was type V. CONCLUSIONS: Nonarticulated hip
      distraction without soft tissue release seems to be a valid treatment option in
      cases with Legg-Calve-Perthes disease where poor results are expected from
      conventional treatment.

PMID- 21857445
TI  - Diagnosis and treatment of femoroacetabular impingement in Legg-Calve-Perthes
      disease.
AB  - Residual hip deformities secondary to Legg-Calve-Perthes disease (LCPD) include
      growth disturbance of the proximal femoral physis with nonspherical femoral head,
      overriding greater trochanter with short femoral neck and secondary remodeling of
      the acetabulum. These deformities can change the mechanical function of the hip
      joint and contribute to femoroacetabular impingement. All these deformities need
      to be recognized and its contribution to the patient's symptoms understood before
      a treatment strategy can be planned. Safe surgical dislocation of the hip allows
      for complete inspection of the hip joint and dynamic assessment of
      femoroacetabular contact during hip motion. The goals of this paper are to review
      the pathophysiology, clinical presentation, imaging findings, and the management
      of femoroacetabular impingement in patients with LCPD. We sought to present our
      treatment philosophy for patients who were diagnosed and treated for LCPD as a
      child and present with femoroacetabular impingement as adolescents and young
      adults.

PMID- 21857446
TI  - Role of total hip arthroplasty and resurfacing in Legg-Calve-Perthes disease.
AB  - Hip replacement arthroplasty is a very reliable and effective therapeutic
      modality for patients with end-stage degenerative coxarthrosis secondary to Legg
      Calve-Perthes disease (LCPD). Long-term results of the conventional total hip
      arthroplasty for patients with LCPD have been reported to be satisfactory similar
      to those for patients with primary arthritis. For selective patients, resurfacing
      arthroplasty can be performed successfully. We described special aspects of
      patients with LCPD in conventional total hip arthroplasty and resurfacing
      arthroplasty.

PMID- 21857449
TI  - New technique for laparoscopic management of potentially malignant and complex
      renal cyst.
AB  - INTRODUCTION: Laparoscopic management for potentially malignant renal cysts can
      pose a therapeutic dilemma, because it is difficult to resect the cystic tumor
      without spillage of its content. We developed a new technique to minimize the
      risk of inadvertent intraoperative rupture of the cyst capsule by using a
      S.A.N.D. balloon catheter. MATERIALS AND METHODS: A 45-year-old male presented
      with an indeterminate renal cyst, and was underwent laparoscopic partial
      nephrectomy. The cyst wall was sandwiched and sealed firmly between the 2
      balloons, which are equipped at the tip of a S.A.N.D. balloon catheter. The
      cystic tumor was completely excised without renal pedicle clump. RESULTS: The
      operation was successful without intraoperative morbidity and no intraperitoneal
      spillage of cyst content occurred. CONCLUSIONS: We demonstrate how to avoid the
      intraoperative rupture of the cyst capsule by using a S.A.N.D. balloon catheter.
      This technique is safe and feasible, while maintaining the benefits of minimal
      invasiveness.

PMID- 21857450
TI  - Finding a lost needle in laparoscopic surgery.
AB  - BACKGROUND: A lost needle during laparoscopic surgery is an uncommon major
      surgical problem. Finding and retrieval can be a challenge, whereas failure to do
      so carry potentially serious clinical and medicolegal implications. This study
      aims to investigate the application of a new device to retrieve lost needles
      intraoperatively compared with traditional management. METHOD: A literature
      search was performed to locate articles on lost surgical needles associated with
      laparoscopic surgery. A laparoscopic magnet was designed and tested based on a
      case report and an animal experiment. RESULTS: The laparoscopic magnet was a fast
      and safe method for retrieval of lost surgical needles during laparoscopic
      surgery. CONCLUSIONS: Lost needles during laparoscopic surgery can be located and
      retrieved by various methods. We found the laparoscopic magnet to be the safest
      and most efficient way of retrieving lost needles intraoperatively.

PMID- 21857451
TI  - Laparoendoscopic single site liver resection for recurrent hepatocellular
      carcinoma in cirrhosis: first technical note.
AB  - INTRODUCTION: Single port access laparoscopic redo liver resection for
      hepatocellular carcinoma on cirrhosis through a single transumbilical skin
      incision has not been reported in the literature so far. METHODS: A wedge
      resection of segment III lesion with a laparoendoscopic single site surgical
      incision is described in detail analyzing the technical aspects of the procedure.
      RESULTS: There were no intraoperative complications with no intraoperative or
      perioperative blood transfusions. A Pringle maneuver was not used. Operating time
      was 130 minutes. The patient had an uneventful postoperative course and was
      discharged on the second postoperative day. The surgical resection margin was not
      invaded and had a width of 1.8 cm. CONCLUSIONS: In this case report, we found
      that liver resection performed by laparoendoscopic single site surgery for
      peripherally located hepatocellular carcinoma on cirrhosis seems a feasible
      technique. Such technique is technically demanding and should be undertaken only
      with proper training and in high volume centers, by surgeons with expertize in
      both liver and advanced laparoscopic surgery.

PMID- 21857452
TI  - Intraluminal resection of gastric tumors using intragastric trocar technique.
AB  - INTRODUCTION: We are presenting our experiences with combined laparoscopic and
      endoscopic approaches applied to the minimally invasive intragastric resection of
      the gastric tumors. PATIENTS AND METHOD: We performed the above-mentioned
      combined intragastric resection in 7 patients. The intragastric resection is only
      used with posterior gastric wall tumors and tumors located near the cardia and
      the pylorus. For this approach, only 1 trocar is placed into the stomach to
      intragastrically introduce the endostapler. We used 2 trocars (5 mm) into the
      abdominal cavity for laparoscopy. RESULTS: We have performed the combined
      laparoscopic and endoscopic intragastric resection in 7 patients. The tumor size
      was 38 +/- 7 mm (28-48 mm). The histology revealed 6 gastrointestinal stromal
      tumors and 1 leiomyoma. All 7 patients began eating and drinking on the second
      postoperative day. None of the patients showed any intraoperative or
      postoperative complications. The median postoperative hospital stay was 6.1 days
      (4-7 d). CONCLUSIONS: The combined intraluminal resection using 1 intragastric
      trocar of potential benign posterior gastric wall tumors, of tumors near the
      cardia and the pylorus is a safe surgical procedure with low invasivity and
      morbidity.

PMID- 21857453
TI  - Laparoscopically excised completely isolated enteric duplication cyst in adult
      female: a case report.
AB  - Enteric duplication cysts are hollow, epithelium-lined, cystic, spherical, or
      tubular structures that are firmly attached to the wall of the gastrointestinal
      tract. Commonly they are supplied by surrounding mesenteric blood vessels.
      However, completely isolated duplication cysts do not communicate with the normal
      bowel segment and have their own exclusive blood supply. They are a very rare
      variety of gastrointestinal duplications. In the English medical literature there
      are 5 earlier reported cases: 4 in pediatrics and 1 in an adult male age 28
      years. We report a case of a 27-year-old female patient presenting with a
      completely isolated (noncontiguous) enteric duplication cyst with its own
      vascular pedicle. This case represents a rare clinical example of an isolated
      enteric duplication cyst removed by laparoscopic excision. To the best of our
      knowledge, this is the first reported case of its kind in an adult female and the
      first case to use laparoscopy to remove the cyst.

PMID- 21857454
TI  - Therapy of solitary cecal diverticulitis in a young patient with laparoscopic
      right hemicolectomy.
AB  - Cecal diverticulum of colon is a relatively rare and benign condition in the
      western world. The reported frequency is approximately 1 in 300 appendectomies.
      They are usually asymptomatic but it may cause inflammatory, hemorrhagic, or
      perforatory complications. It is often clinically indistinguishable from acute
      appendicitis. The diagnosis is almost made intraoperatively. We present a 21-year
      old female patient who admitted to our emergency unit with right lower quadrant
      abdominal pain. Diagnostic laparoscopy was performed due to suspicious acute
      appendicitis. During exploration, an inflammatory mass originated from cecum was
      noticed. Laparoscopic right hemicolectomy was performed due to suspicious
      malignant mass. The postoperative course was uneventful. Although radiologic
      techniques are improved; the diagnosis of solitary cecal diverticulum is
      difficult. The choice of surgical therapy is controversial. The therapy is ranged
      from a simple diverticulectomy to right hemicolectomy. Diagnostic laparoscopy can
      help the surgeon in the diagnosis of right lower quadrant pain and therapy of
      solitary cecal diverticulitis.

PMID- 21857455
TI  - Laparoscopic-assisted spleen-preserving and pylorus-preserving total
      pancreatectomy for main duct type intraductal papillary mucinous tumors of the
      pancreas: a case report.
AB  - Minimally invasive and function-preserving pancreatectomy would be the ideal
      approach for benign and borderline malignant tumors of the pancreas. Total
      pancreatectomy can be indicated for the main duct type of intraductal papillary
      mucin-producing tumor (IPMT) to achieve radical resection. Recently, several
      studies advocating total pancreatectomy in IPMT have been published, but they are
      all believed to be done by conventional laparotomy. Herein, we report a case of a
      72-year-old female patient who successfully underwent laparoscopic-assisted total
      pancreatectomy with the spleen and pylorus preserved in borderline malignant main
      duct type IPMT. A marginal ulcer around the duodenojejunostomy was developed, but
      managed by a proton-pump inhibitor. She was discharged 20 days after surgery. She
      was followed for more than 2 years without evidence of tumor recurrence. Her
      blood sugar level was well controlled by insulin pump therapy and image study
      showed well-preserved spleen function.

PMID- 21857456
TI  - Laparoscopic anatomic S4 segmentectomy for hepatocellular carcinoma.
AB  - INTRODUCTION: When hepatocellular carcinoma (HCC) is located in the S4 segment,
      resection of only the S4 segment is more beneficial than performing a left
      hemihepatectomy as resection of only the S4 segment preserves the liver volume of
      the left lateral segment. We report here a case of performing a total
      laparoscopic S4 segmentectomy with resection of the middle hepatic vein, which
      was in contact with the HCC. METHODS: A 63-year-old man was admitted for an
      incidentally detected hepatic mass. The preoperative liver function was Child
      Pugh class A. An abdominal computed tomographic scan revealed a 3.2 cm HCC that
      was located in the superior portion of segment 4 and the HCC was in contact with
      the middle hepatic vein. A laparoscopic extended S4 segmentectomy was performed.
      RESULTS: The operative time was 440 minutes. The estimated intraoperative blood
      loss was approximately 800 mL; no intraoperative transfusion was necessary. The
      patient was discharged on the 10th postoperative day without any postoperative
      complications. CONCLUSIONS: This case shows the feasibility of performing a
      laparoscopic S4 segmentectomy in selected patients.

PMID- 21857457
TI  - Magnifying endoscopy for monitoring intestinal adaptation: a case report.
AB  - A 33-year-old Chinese man with short bowel syndrome received intestinal
      rehabilitation therapy. We observed microscopically morphologic changes of
      remnant small intestine by magnifying endoscopy and histopathologic examination
      before and after 3 courses of treatment. The results revealed that the 2 methods
      have a fairly good correlativity, and magnifying endoscopy examination of
      intestinal adaptation in patients with short bowel syndrome possesses great
      applicative value.

PMID- 21857458
TI  - Laparoscopic reduction of an internal hernia of transverse colon through the
      foramen of Winslow.
AB  - Large bowel obstruction by incarceration in the lesser sac through the foramen of
      Winslow is exceedingly rare and often associated with nonviable bowel at the time
      of operation according to older reports. In modern times, widespread availability
      of computed tomography (CT) for investigation of the acute abdomen may decrease
      the necessity of bowel resection in these cases. Here, we present a case of
      laparoscopic reduction of viable transverse colon from the lesser sac in a young
      woman. With the diagnosis suggested by CT, we were able to approach the case with
      two five millimeter working ports and 1 optical port, reducing the hernia by
      means of traction on the distal limb of transverse colon. The patient recovered
      well and was discharged on day 4 postoperative after bowel movement was achieved.
      Internal hernia represents one of the few cases in which laparoscopy may be the
      preferred approach to large bowel obstruction.

PMID- 21857459
TI  - Trans-areola single-incision endoscopic thyroidectomy.
AB  - AIM: Single-incision laparoscopic surgery has been successfully applied to
      abdominal general and bariatric procedures with advantages of less morbidity over
      conventional laparoendoscopic surgery. Minimally invasive and laparoendoscopic
      procedures have also recently been expanded for thyroid surgery. We report the
      first case of trans-areola single-incision endoscopic thyroidectomy (TASIET) in
      the world. CASE: A 20-year-old female patient presented with a solitary left
      thyroid nodule. Single-incision endoscopic thyroidectomy was successfully
      performed by an incision bordering the left breast areola. Two adjacent 10 mm and
      5 mm trocars were used for the placement of a 10 mm videoscope (30 degrees) and
      ultrasonic shears, respectively. A single narrow tunnel was first created from
      the areola to the neck, and the oval space between platysma and strap muscles in
      the anterior neck was dissected. Left lobectomy was accomplished after the strap
      muscles and thyroid were suspended with transcutaneous sutures. The specimen was
      removed in a self-made plastic bag through the 10 mm incision. RESULTS:
      Anatomical delineation of the left recurrent laryngeal nerve and parathyroid
      glands were satisfactory. Blood loss was less than 20 mL. The total operative
      time was 156 minutes. The patient required no administration of analgesics and
      was discharged postoperatively without complications. After 3 months follow-up,
      cosmetic outcome was excellent with a small periareaolar incision and no cervical
      scar. Pathology revealed a benign follicular adenoma. CONCLUSION: Our first
      TASIET is feasible with excellent cosmesis and advantages of minimally access
      surgery. Ongoing studies with TASIET are in progress to define the optimal
      indications and patient selection criteria for this new thyroidectomy technique.

PMID- 21857460
TI  - Infarction of a lipoma of the lesser omentum: laparoscopic treatment of a rare
      condition.
AB  - Infarction of the lesser omentum is an infrequent occurrence and is unfamiliar to
      most clinicians. Patients with this condition present with insidious epigastric
      pain, peritonitis on examination, and a normal white blood cell count. The
      computed tomographic scan reveals a focal ill-defined inflammatory mass with
      attendant fat stranding along the lesser curve of the stomach. In most patients,
      the diagnosis is secured at operation, although analgesics alone might be
      sufficient for management of this benign inflammatory condition. We present a
      case with the classic findings that was managed laparoscopically. Greater
      familiarity with focal infarction of lesser omental fat might lead to more
      nonoperative management in the future.

PMID- 21857461
TI  - Entirely robotic total pelvic exenteration.
AB  - OBJECTIVE: We present an entirely robotic total pelvic exenteration and extended
      lymphadenectomy with "barreled ureterocutaneostomy" and end colostomy for
      recurrent endometrial cancer. In 1948, Brunschwig first described a pelvic
      exenteration as treatment of advanced recurrent malignancy in the pelvis.
      Currently it represents the only potentially curative option for patients with
      recurrent endometrial cancer. METHODS: A 69-year-old female with perineal
      recurrence invading urethral and vaginal walls, lower rectum and anal sphincter
      was the perfect candidate for total pelvic exenteration. RESULTS: Total operative
      time was 250 minutes, with a console time of 175 minutes. The estimated blood
      loss was 365 mL. CONCLUSIONS: Good oncological results are expected after robotic
      total pelvic exenteration owing to the accurate, precise dissection and the
      extension of lymphadenectomy in the narrow space of the deep pelvis similar to
      robotic prostatectomy and total mesorectal excision.

PMID- 21857462
TI  - Laparoscopic repair of esophageal perforation due to Boerhaave syndrome.
AB  - Boerhaave syndrome is the spontaneous transmural rupture of the esophagus due to
      an increase in intraesophageal pressure when vomiting against a closed glottis.
      There are various methods of managing it, with the main principles of limiting
      sepsis, draining the area, and maintaining nutrition. These include conservative
      management, open repair with drain insertion, and laparoscopic repair, depending
      on the timing of presentation and the amount of sepsis. Although the gold
      standard is open thoracotomy and/or laparotomy, we present a case where an
      esophageal rupture, presenting within 24 hours and hemodynamically stable, was
      managed with laparoscopic repair and drain insertion with good results. There is
      a paucity of literature regarding this mode of management and we have discussed
      the various options available in literature. We conclude that this is a safe and
      viable option in the management of Boerhaave syndrome in a nonseptic patient
      presenting early.

PMID- 21857463
TI  - Successful management of staple line leak after laparoscopic sleeve gastrectomy
      with vascular plug and covered stent.
AB  - PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is a feasible option for morbid
      obesity. But gastric leak is one of the most dreadful complications. We report
      our experience of staple line leak, which was managed successfully with vascular
      plug and covered stent. METHODS: A staple line leak occurred after LSG. Followed
      attempts of reoperation, drainage procedures of abscess cavity, and repeated
      endoscopic treatments were all unavailing. Finally, vascular plug was placed at
      fistula tract and consequent endoscopic covered stent placement could propose the
      solution. RESULTS: Granulation tissue, which occluded the fistula tract was
      identified by computed tomographic scan 2 weeks after stent placement. Leak
      healed successfully, and the patient discharged safely a week after stent
      removal. CONCLUSIONS: We consider inducing granulation tissue by applying
      vascular plug at fistula tract in combination with covered stent placement, which
      is a safe and effective therapeutic option for management of intractable staple
      line leak after LSG.

PMID- 21857464
TI  - Gastric perforation after laparoscopic splenectomy and esophagogastric
      devascularization for portal hypertension: report of a case.
AB  - INTRODUCTION: Laparoscopic splenectomy and esophagogastric devascularization
      (LSED) has been widely used as a novel surgical intervention for portal
      hypertension, especially in China. Gastric perforation is a rare postoperative
      complication in this procedure. Symptoms consist of hyperpyrexia, abdominal pain,
      and abdominal coffee-ground drainage. There are 2 known risk factors including
      portal hypertensive gastropathy and poor blood supply to the stomach after
      operation. METHODS: We described a case of gastric perforation in a male patient
      who underwent LSED for portal hypertension and severe gastroesophageal varices,
      secondary to liver cirrhosis. At the seventh day after surgery, some symptoms
      appeared including fever, left abdominal pain, refractoriness hiccough, and
      abdominal distention. The diagnosis of gastric perforation was made by upper
      gastrointestinal tract x-ray radiography. The patient was cured after
      approximately 2 months by receiving sufficient abdominal drainage, nutritional
      support, antihepaticcoma, and other expectant treatments, which was confirmed by
      upper gastrointestinal tract radiography. CONCLUSIONS: Gastric perforation is a
      rare but life-threatening complication after LSED. It is easy to diagnose by its
      typical symptoms and signs. Although it seems that the emergency laparoscopic
      operation is the best choice, in view of the high risk due to poor liver
      function, conservation treatment is also a good selection.

PMID- 21857465
TI  - Laparoscopic-assisted proximal gastrectomy in an obese patient with gastric
      cancer and myasthenia gravis.
AB  - The patient is a 61-year-old man who had previously undergone an extended
      thymectomy for myasthenia gravis. Endoscopic examination during a routine follow
      up visit revealed early gastric cancer in the proximal portion of the stomach. To
      undergo resection the patient received general and epidural anesthesia. The
      conditions were unfavorable for laparoscopic-assisted surgery because he had a
      body mass index of 33 and muscle relaxants could not be used. Pneumoperitoneum
      was induced with carbon dioxide, and the abdominal wall was lifted. An adequate
      working space was secured in the upper abdomen and proximal gastrectomy was
      successfully performed.

PMID- 21857466
TI  - "Laparoscopic excision of a large ovarian cyst herniating into the inguinal
      canal: a rare presentation".
AB  - Inguinal hernia repair is one of the most common operation in surgical practice.
      Despite its common occurrence, hernia often poses a surgical dilemma even for a
      skilled surgeon. The unexpected hernial content constitutes one of these cases.
      Although the often-reported, unusual contents of a hernia sac include ovary,
      fallopian tube, vermiform appendix, Meckel diverticulum, and urinary bladder, the
      herniation of a large ovarian cyst into the inguinal canal has been hardly
      reported. Majority of the ovarian cysts are asymptomatic or present with vague
      lower abdominal pain, whereas the presentation of a large ovarian cyst as an
      inguinolabial swelling as in our patient is extremely rare. We present here one
      of the few reported cases of a laparoscopic excision of a large ovarian cyst
      herniating into the inguinal canal and discuss the pathogenesis of an ovarian
      cyst as hernial content, the advantages and concerns of a laparoscopic approach
      in resecting large ovarian cysts, and simultaneous management of the inguinal
      hernia.

PMID- 21857467
TI  - Difficult laparoscopic cholecystectomy: current evidence and strategies of
      management.
AB  - Laparoscopic cholecystectomy is the treatment of choice for gall bladder stone
      disease. Difficult cholecystectomy is associated with serious complications and a
      high conversion rate. The aim of this study was to review the current strategies
      to manage difficult cholecystectomy. METHODS: A Medline search was conducted to
      review all published English literatures relevant to difficult cholecystectomy
      through 1993 to 2009. The search words were "laparoscopic cholecystectomy,"
      "difficult cholecystectomy," "difficult laparoscopy," "subtotal laparoscopic
      cholecystectomy," "fundus first cholecystectomy," and "causes of conversion of
      laparoscopic cholecystectomy." RESULTS: Ninety-one studies, which included
      324,553 patients, were selected for this review. Five major categories of
      difficulty were identified. Conversion rate and iatrogenic injuries during
      laparoscopic cholecystectomy are still high despite significant improvement over
      the last 10 years. Depending on the technique of cholecystectomy, the degree of
      gall bladder inflammation, patient comorbidities, and surgical experience, the
      conversion rate was reported between 0.18% and 30%, whereas the incidence of
      iatrogenic injuries was from 0% to 0.6%. Subtotal cholecystectomy, antegrade and
      fundus first techniques, and peroperative cholangiogram were associated with
      lower complications and conversion rate. Risk factors for difficulty were male
      sex, increased age, acute and thick wall chronic cholecystitis, wide and short
      cystic duct, cholecystodigestive fistula, previous upper abdominal surgery,
      obesity, liver cirrhosis, anatomic variation, cholangiocarcinoma, and low
      surgeon's caseload. CONCLUSIONS: No consensus is found among surgeons on how to
      manage difficult laparoscopic cholecystectomy. Iatrogenic injuries and conversion
      rate can be reduced depending on the surgeon's experience, special techniques,
      and intraoperative investigations. Subtotal cholecystectomy, antegrade or fundus
      first techniques, and peroperative cholangiogram significantly reduced the
      complications and conversion rate.

PMID- 21857468
TI  - Safe techniques for endoscopic resection of gastrointestinal lipomas.
AB  - PURPOSE: Gastrointestinal (GI) lipomas are rare, benign, slowly growing,
      submucosal tumors, which can either be incidentally found as silent tumors of the
      GI tract or be the cause for GI bleeding, anemia, intussusception, and bowel
      obstruction. Endoscopic removal is a valid alternative to surgical resection of
      these tumors. In the recent past, many submucosal lipomas were for the most part
      resected surgically due to the risk of perforation using endoscopy. There are
      newer techniques available to allow safe endoscopic removal of these lesions. We
      present 3 successful techniques tailored to the location of the lipoma and size.
      METHODS: In our unit, 3 symptomatic GI lipomas were referred to us for surgical
      resection, 2 originating from the duodenum and 1 from the cecum were diagnosed
      and resected under endoscopic ultrasound and endoscopy. We performed 3 different
      techniques to remove these lipomas. One of the lipomas in the duodenum was in the
      duodenal bulb. It was mobile and 3 cm in size. We attempted to remove this broad
      based lipoma by snare and cut technique after its borders were elevated with
      injection of saline and epinephrine. The second duodenal lipoma was 1.5 cm. This
      pedunculated lipoma was located in the second portion, on the pancreatic side of
      the duodenum proximal to ampulla. This lipoma was lifted up with a snare and its
      base was cauterized resulting in successful removal. The third GI lipoma was 3.5
      cm in size pedunculated and located in the cecum. The base of this pedunculated
      lipoma was ligated with poly loop device and endoclip resulting in ischemia and
      spontaneous separation of the lipoma from the colonic wall. All cases were
      revisited with follow-up endoscopy. All 3 methods, when used selectively, were
      found to be very safe and effective. RESULTS: All 3 lesions were successfully
      removed and histopathologically confirmed to be lipomas. After endoscopic
      removal, no complications were observed. CONCLUSIONS: Carefully selected GI
      lipomas, which in the past have required surgical resection due to high risk for
      perforation can be endoscopically removed with great success.

PMID- 21857469
TI  - Prospects of robotic thyroidectomy using a gasless, transaxillary approach for
      the management of thyroid carcinoma.
AB  - PURPOSE: Robotic surgical systems are among the most innovative surgical
      developments and have radically promoted the use of minimally invasive
      techniques. Robotic technologies using different approaches have also been
      applied to thyroid surgery. Recently, the authors described a novel robotic
      surgical method for thyroid surgery based on a gasless, transaxillary approach
      (TAA), and have since serially reported on its technical feasibility and safety.
      Here, the authors report their experience of a consecutive series of 1000 cases
      treated using robotic thyroidectomy, and demonstrate its use for the surgical
      management of thyroid cancer. PATIENTS AND METHODS: From October 2007 to November
      2009, 1000 patients with thyroid cancer underwent robot-assisted endoscopic
      thyroid surgery using a gasless TAA. All patients were selected using
      predetermined inclusion criteria after considering surgical risk, and all
      procedures were completed successfully using the da Vinci S or Si surgical system
      (Intuitive Surgical, Sunnyvale, CA). Patient's clinicopathologic characteristics,
      operation types, operation times, numbers of retrieved lymph nodes (LNs),
      postoperative hospital stays, complications, and short-term follow-up results
      were analyzed. RESULTS: Mean patient age was 39.1 +/- 9.6 years and the male-to
      female ratio was 1:12.6 (73:927). Six hundred twenty-seven patients underwent
      less than total and 373 patients underwent bilateral total thyroidectomy.
      Ipsilateral central compartment node dissection was conducted in all 1000 cases
      and additional lateral neck node dissection was conducted in 36 of the 1000
      patients. Mean operation time was 136.7 +/- 44.4 minutes and mean postoperative
      hospital stay was 3.0 +/- 0.45 days. No serious postoperative complication
      occurred, except 3 cases of recurrent laryngeal nerve injury, and 1 case of
      Horner syndrome. Mean tumor size was 0.79 +/- 0.6 cm and papillary thyroid
      microcarcinoma was in 752 cases (75.5%). The mean number of retrieved central LNs
      per patient was 4.62 +/- 3.14. Central neck LN metastasis occurred in 361(36.1%)
      and lateral neck LN metastasis in 36 cases (3.6%). According to tumor nodes
      metastasis staging, 847 patients (84.7%) were of stage I, 144 patients (14.4%)
      were of stage III, and 9 patients (0.9%) were of stage IVA. CONCLUSIONS: The
      authors conclude that robotic thyroidectomy using a gasless TAA is a feasible,
      safe, and promising surgical alternative for selected patients with low-risk
      thyroid cancer, and recommend that the inclusion criteria of this technique be
      gradually extended to advanced thyroid cancer given suitable operator experience
      and future developments in robotic systems and instrumentation.

PMID- 21857470
TI  - Bilateral axillo-breast approach robotic thyroidectomy.
AB  - BACKGROUND: Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT)
      has good postoperative and excellent cosmetic outcomes. This study aimed to
      describe the techniques for robotic BABA thyroidectomy in detail (see Videos,
      Supplemental Digital Content 1, http://links.lww.com/SLE/A45 and Supplemental
      Digital Content 2, http://links.lww.com/SLE/A46). METHODS: Between 2008 and 2010,
      704 patients underwent BABA RoT. The mean patient age was 38.9+/-9.1 years and
      the male-to-female ratio was 1:8.0. BABA RoT is an oncoplastic thyroid surgery
      using BABA and da Vinci robot system with low pressure of CO2 gas insufflations.
      RESULTS: The operation types were as follows: total thyroidectomy with or without
      neck dissection (n=556, 78.9%), subtotal thyroidectomy (n=67, 9.5%), lobectomy
      (n=73, 10.4%), and completion thyroidectomy (n=8, 1.1%). CONCLUSIONS: BABA RoT
      yields good postoperative outcomes. With excellent cosmetic outcomes, this
      technique may be a suitable alternative for patients with thyroid diseases.

PMID- 21857471
TI  - Robotic facelift thyroidectomy: patient selection and technical considerations.
AB  - OBJECTIVES: A series of remote access thyroidectomy techniques, some using a
      surgical robot, have been introduced in the last decade. Most of these approaches
      require awkward positioning, use unfamiliar dissection planes, and have been
      associated with a number of significant complications. As a result, acceptance
      has been limited. We describe technical details and patient selection criteria of
      a recently described robotic facelift thyroidectomy (RFT) approach that avoids
      these pitfalls. DESIGN: Analysis of preclinical and clinical studies. METHODS:
      Inanimate and cadaver dissection studies and clinical implementation were
      pursued. A 3-arm RFT technique with a 30-degree offset base location proved
      optimal. Supine positioning with arms tucked and the patient in slight
      Trendelenburg position facilitated the dissection of the optical pocket.
      Demographic and surgical data that have been obtained and considered include
      patient age, sex, body mass index, pathology, and complications. RESULTS: A
      series of consecutive RFT procedures has been accomplished in a limited
      population of patients. All cases were completed robotically with no conversions
      to open surgery necessary. All but the first case was accomplished on a
      drainless, outpatient basis. CONCLUSIONS: A RFT technique that is gasless and
      uses a single access port in the postauricular crease and occipital hairline
      location is feasible, technically less challenging than other remote access
      methods, and safe. Further study in an expanded patient population and in
      additional high-volume thyroid centers is warranted. See the videos, Supplemental
      Digital Content 1, http://links.lww.com/SLE/A36andSupplementalDigitalContent2,
      http://links.lww.com/SLE/A37.

PMID- 21857472
TI  - Laparoscopic retroperitoneal adrenalectomy.
AB  - Laparoscopic adrenalectomy has largely replaced open adrenalectomy for resection
      of adrenal tumors, which are not adrenocortical cancer or malignant
      pheochromocytoma. Laparoscopic retroperitoneal adrenalectomy is a particularly
      useful technique in patients with tumors <7 cm and body mass index <45 kg/m2.
      When compared with laparoscopic transabdominal adrenalectomy, the laparoscopic
      retroperitoneal technique leads to reduced operating times, avoidance of intra
      abdominal adhesions and irradiated fields, potentially less postoperative pain,
      and improved intraoperative hemostasis and visualization. The technique involves
      placement of 3 ports, dissecting the retroperitoneal space, identifying and
      ligating the adrenal vein, and removing the attachments to the adrenal gland. See
      the video, Supplemental Digital Content 1, http://links.lww.com/SLE/A38.

PMID- 21857473
TI  - Robot-assisted adrenalectomy.
AB  - Currently laparoscopic adrenalectomy (LA) is regarded as the preferred surgical
      approach for the management of most adrenal surgical disorders. Despite the
      benefits of LA, the procedure has shortcomings that are shared by other
      laparoscopic techniques. Commonly noted problems include the absence of 3
      dimensional perception, reduced dexterity, and poor ergonomics for the surgeon.
      Recently, robotic technology has been introduced into laparoscopic clinical
      practice. The requirement for precise surgery in adrenalectomy is important, and
      the introduction of robotically assisted LA offers new possibilities. This review
      summarizes current available data regarding robotic adrenalectomy, including its
      indications, advantages, limitations, and comparison with conventional
      laparoscopic adrenalectomy. See the videos, Supplemental Digital Content 1,
      http://links.lww.com/SLE/A33, Supplemental Digital Content 2,
      http://links.lww.com/SLE/A34 and Supplemental Digital Content 3,
      http://links.lww.com/SLE/A35.

PMID- 21857474
TI  - Percutaneous and video-assisted ablation of endocrine tumors: liver, adrenal, and
      thyroid.
AB  - Radiofrequency ablation (RFA) relies on cell destruction using heat, which is
      generated by the vibration of electrons as a result of high-frequency electrical
      energy. RFA was initially employed for the treatment of arrhythmogenic cardiac
      lesions. It has since been used to treat solid tumors of various organs, both
      primary and metastatic. Here we review the manner in which RFA technology
      delivered through minimally invasive techniques has been applied to endocrine
      problems and discuss some technical points.

PMID- 21857475
TI  - Long-term outcomes of laparoscopic wedge resection for gastrointestinal stromal
      tumors of the stomach of less than 5 cm in diameter.
AB  - BACKGROUND: Few long-term results of laparoscopic resection for gastrointestinal
      stromal tumors (GISTs) of the stomach have been established to evaluate technical
      safety and oncologic feasibility. METHODS: Between April, 1998 and October, 2008,
      data of 18 patients who underwent laparoscopic resection of GISTs of <5 cm in
      diameter were reviewed. RESULTS: There were 10 men and 8 women with average age
      of 66.5 years. Estimated blood loss was minimal, and average operation time was
      99.2 +/- 30.5 minutes. There were no major intraoperative complications or
      conversions to open approach. Oral feeding started 2 to 4 days after operation,
      and the mean hospital stay was 10.1 +/- 5.5 days. There were no major
      postoperative complications except for 1 patient who suffered from aspiration
      pneumonia. Tumor size was 3.7 +/- 1.1 cm (range, 1.5 to 7.0 cm), and all patients
      had free surgical margins. During long-term follow-up (average 54.6 mo), no
      complications occurred except for liver metastasis in only 1 patient who was
      responding well to imatinib therapy. CONCLUSIONS: Laparoscopic wedge resection of
      GISTs of <5 cm in diameter is a safe and oncologically feasible technique
      offering good long-term outcomes.

PMID- 21857476
TI  - Simultaneous laparoscopic totally extraperitoneal repair of bilateral inguinal
      hernia: review of 1 surgeon experiences.
AB  - BACKGROUND: This study evaluated the outcomes of laparoscopic totally
      extraperitoneal (TEP) simultaneous bilateral hernia repair with regard to the
      effectiveness and the complications compared with those of unilateral
      laparoscopic TEP hernia repair. METHODS: One hundred twelve patients underwent
      laparoscopic TEP for bilateral inguinal hernia and 767 patients underwent
      laparoscopic TEP for a unilateral hernia from March 2004 to January 2010.
      RESULTS: The mean age of the patients was older in bilateral group than that in
      the unilateral group, and the proportion of female patients was lower in the
      bilateral group. The distribution of the types of hernia was different in both
      the groups (P<0.001). The mean operation time and the mean patient cost for TEP
      in the bilateral group were 1.5 times longer and more expensive than that in the
      unilateral group. However, there were no differences in the mean number of
      hospital days and postoperative complications. There was 1 recurrence in the
      bilateral group, but it had no statistical significance (P=0.127). CONCLUSIONS:
      Laparoscopic TEP repair is safe and feasible for treating bilateral inguinal
      hernia. Bilateral repair also has some advantages such as no additional
      admission, a decreased operation time, and cost-effectiveness.

PMID- 21857477
TI  - Long-term results of laparoscopic Nissen fundoplication with or without short
      gastric vessels division.
AB  - BACKGROUND: It has been claimed that division of the short gastric vessels (SGV)
      during laparoscopic Nissen fundoplication (LNF) could reduce the risk of
      postoperative dysphagia. The aim of this study was to compare patients who
      underwent LNF with (SGV+) or without (SGV-) SGV division in our institution and
      present long-term results. MATERIALS AND METHODS: Retrospective case note review
      study of patients undergoing LNF with or without division of the SGV. Outcomes
      included DeMeester score, low esophageal sphincter resting pressure, and upper
      endoscopy. Operative time and patient satisfaction were also recorded. RESULTS:
      Between February 2004 and February 2007, a total of 123 patients underwent LNF,
      59 (48.0%) SGV- and 64 (52.0%) SGV+. The 2 groups were statistically comparable.
      There was no significant difference about median DeMeester score, low esophageal
      sphincter resting pressure, and long-term satisfaction score between the 2 groups
      at a mean of 4 years of follow-up (range, 36 to 60 mo). The mean operative time
      was statistically significantly lower in the SGV- patients (90 vs. 115 min,
      P=0.04). CONCLUSIONS: Our experience suggests that LNF without division of SGV
      provides a good clinical and functional outcome, whereas division of the SGV is
      associated with longer operative times.

PMID- 21857478
TI  - Transperitoneal laparoscopic adrenalectomy for adrenal metastasis.
AB  - AIM: The treatment of adrenal metastasis using laparoscopic surgery is evolving.
      The aim of this study was to evaluate the feasibility of laparoscopic
      adrenalectomy (LA) in patients who have adrenal metastases. METHODS: From
      September 1998 to November 2010, 12 patients underwent LA for adrenal metastatic
      tumors. Three cases were bilateral and 9 were unilateral. We retrospectively
      reviewed the clinical and histopathologic data of all 12 patients. RESULTS: The
      operations of all the 12 cases were successful. There were no intraoperative
      complications. The mean follow-up time was 17.2 months (range, 2 to 56 mo). We
      found no intraperitoneal and/or port-site recurrence. One patient had died from
      metastatic disease. CONCLUSIONS: Our experience leads us to feel that LA is
      feasible when the primary tumor is well controlled, there are no other metastases
      clinically and radiologically, when the adrenal metastasis is confined to the
      adrenal gland, and there is no radiologic evidence of local extension into tissue
      around the adrenal gland.

PMID- 21857479
TI  - Percutaneous endoscopic gastrostomy and peristomal infection: an avoidable
      complication with the use of a minimum skin incision.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a fast and simple
      method. Although considered safe, PEG is associated with many potential
      complications. Peristomal infection is the complication most frequently reported.
      OBJECTIVE: To analyze patients who underwent PEG and the association of
      peristomal infection with the extent of skin incision (SI) and usage of
      prophylactic antibiotics (PA). METHODS: A retrospective review of the records of
      120 patients who underwent PEG was carried out. Patients were divided into 3
      subgroups: (1) Patients with SI 10 mm/without PA, (2) Patients with SI up to 5
      mm/without PA, and (3) Patients with SI up to 5 mm/with PA. RESULTS: Peristomal
      infection occurred in 12.8% of patients from subgroup 1, and in 2.2% of patients
      from subgroup 2. There was no infection in subgroup 3. Peristomal infection was
      associated with the SI extent (P=0.01) and there was no association with PA
      (P=0.3). SI >5 mm presented an odds ratio of 10.5 (95% confidence interval, 1.58
      68.42) for the occurrence of peristomal infection. CONCLUSIONS: The use of PA did
      not seem to reduce peristomal infection rates. However, minimal SI was
      significantly associated with reduction of this complication.

PMID- 21857480
TI  - Laparoscopic treatment of presumed perforated appendicitis in consecutive
      patients.
AB  - PURPOSE: The aim of the present study was to determine whether the laparoscopic
      approach is effective in the prompt diagnosis and treatment in consecutive
      patients with presumed perforated appendicitis. METHODS: Over a period of 2
      years, 203 patients were tentatively diagnosed with perforated appendicitis on
      the basis of radiological findings. We performed laparoscopic procedure and
      evaluated the outcomes, including the incidence of alternative pathologies.
      RESULTS: Most patients (188/203, 92.6%) were treated with laparoscopic
      appendectomy or partial cecectomy. Five (2.4%) cases were converted to open
      surgery. Alternative pathologies were found in 24 patients (12%). Of these, 8
      patients underwent laparoscopic ileocolic resection (4 diverticulitis, 2 Crohn
      disease, 1 cystadenoma, and 1 tuberculosis) and 4 patients (2 carcinoid tumors
      and 2 cancers) underwent subsequent laparoscopic right hemicolectomy.
      Complications developed in 23 patients (11.3%). CONCLUSIONS: Laparoscopy for
      presumed perforated appendicitis is an effective treatment and avoids the delay
      arising from a late diagnosis.

PMID- 21857481
TI  - Laparoendoscopic management of concomitant gallbladder stones and common bile
      duct stones: what is the best technique?
AB  - BACKGROUND AND STUDY AIMS: The intraoperative use of endoscopic retrograde
      cholangiopancreatography (ERCP) during laparoscopic cholecystectomy (LC) is a
      safe, single-stage option for the management of concomitant gallstones (GS) and
      common bile duct stones (CBDS). This study aims to compare between 2 techniques
      of combined laparoendoscopic management, which are laparoendoscopic Rendez-vous
      (LC/LERV) technique and standard ERCP after the completion of LC intraoperative
      endoscopic sphincterotomy (IOES). PATIENTS AND METHODS: Patients with GS and
      suspected CBDS were included. They were divided into 2 groups; LC/LERV and
      LC/IOES. Both groups were compared for failure of endoscopic sphincterotomy/stone
      extraction, operative time, conversion rate, mortality/morbidity, and length of
      hospital stay. RESULTS: Between October 2007 and February 2010, 98 patients with
      GS and CBDS were eligible for inclusion in the study. They were prospectively
      randomized into 2 groups; LC/LERV (N=45) and LC/IOES (N=53). There were no
      differences in preoperative parameters between both groups. There was a
      significant difference in operative time (shorter for LC/IOES). No difference was
      noted in success/failure rate, post-ERCP pancreatitis. CONCLUSIONS: Both Standard
      ERCP after the completion of LC and LC/LERV are valid single-session management
      for CBD stones, but LC-ERCP may be preferred.

PMID- 21857482
TI  - Relaparoscopy in minor bile leakage after laparoscopic cholecystectomy: an
      alternative approach?
AB  - PURPOSE: Bile leakage is one of the most important complications of laparoscopic
      cholecystectomy, and it has been recognized as a major clinical challenge during
      the last 2 decades. Although endoscopic and percutaneous interventions are widely
      accepted in the management of bile leakage, relaparoscopy permits the bile
      drainage adequately and gives direct control of bile leakage site in selected
      patients. METHODS: Data for patients with minor bile leakage after laparoscopic
      cholecystectomy were collected from January 2001 to January 2010. Patients were
      categorized in 2 groups, nonoperative and relaparoscopy. Clinical presentation,
      kind of management, and outcomes were evaluated in 2 groups. RESULTS: After a
      total of 2652 laparoscopic cholecystectomies, postoperative minor bile leakage
      occurred in 17 (0.64%) patients. Four patients with minimal leakage were managed
      by percutaneous drainage alone. Endoscopic retrograde cholangiopancreatography
      was applied to 4 patients with jaundice, high output bile fistula, and a patient
      with retained common bile duct stone. Bile leakage was controlled in 3 of the 4
      patients. There were 9 patients in the relaparoscopic group to which 1 patient
      was added after unsuccessful endoscopic intervention. The source of bile leakage
      in the relaparoscopic cases was defined as 50% from cystic duct stump and 50%
      from Luschka or accessory ducts. The success rate of bile leakage control after
      relaparoscopy was 90%. The mean of hospital stay after relaparoscopy was 3 days
      (range, 2-10 d) and after endoscopic retrograde cholangiopancreatography
      intervention or percutaneous drainage was 10 days (range, 3-28 d). CONCLUSIONS:
      Relaparoscopy is an effective procedure in the management of minor bile leakage
      after laparoscopic cholecystectomy and can be an alternative approach in selected
      situations.

PMID- 21857483
TI  - Laparoendoscopic single site surgery can be performed completely with standard
      equipment.
AB  - PURPOSE: To determine the feasibility of laparoendoscopic single site surgery
      (LESS) with nonarticulating instruments and conventional trocars. METHODS: After
      Institutional Review Board approval, a prospective database was used to identify
      30 patients who underwent LESS. All procedures were begun using three 5 mm
      trocars, nonarticulating instruments, and a 5 mm, 30-degree laparoscope. RESULTS:
      Twenty-six patients underwent LESS cholecystectomy. Four patients underwent LESS
      appendectomy; 2 for acute appendicitis and 2 for interval appendectomy. The mean
      patient age was 37.1 +/- 14 years for the cholecystectomy group and 29.3 +/- 2.2
      years for the appendectomy group. Mean body mass index was 28.4 +/- 7 kg/m2 for
      the cholecystectomy group and 25 +/- 5.6 kg/m2 for the appendectomy group. Eight
      patients (31%) undergoing LESS cholecystectomy required an additional 5 mm port;
      6 (26%) required 1 additional port for gallbladder retraction, 1 case (4%)
      required 2 additional ports to control cystic artery bleeding, and 1 case (4%)
      was converted to a traditional 4 trocar cholecystectomy because of chronic
      inflammation and multiple adhesions. None of the patients in the appendectomy
      group required an additional port. The mean operative time was 94 +/- 19 minutes
      for cholecystectomy and 65 +/- 19 minutes for appendectomy. Ninety-two percent
      (N=24) of patients in the laparoscopic cholecystectomy group were discharged
      within 24 hours. One patient underwent postoperative endoscopic retrograde
      cholangiopancreatography with bile duct stone removal and was discharged after 48
      hours. One patient remained until postoperative day 2 for pain control. All
      patients in the LESS appendectomy group were discharged within 24 hours. There
      were no postoperative complications. CONCLUSIONS: Although operative time for
      LESS is increased compared with laparoscopic cholecystectomy and appendectomy,
      LESS can be performed safely. In our institutional experience, LESS was
      successfully performed using standard laparoscopic instruments, laparoscope, and
      trocars. Although longer follow-up is necessary, early data supports the
      feasibility and safety of LESS. A low threshold should exist for the addition of
      extra trocars, especially during a surgeon's early experience with LESS.

PMID- 21857484
TI  - Laparoscopic resection of urachal fistula.
AB  - PURPOSE: Persisting urachal fistula is a rare condition in adults. METHODS: Data
      and outcome in 29 patients who were surgically treated for persisting urachal
      fistula using laparoscopic technique between January 1, 2006 and December 31,
      2009 were retrospectively analyzed. RESULTS: Persisting urachal fistula could be
      diagnosed in all patients by clinical examination and ultrasound. Laparoscopic
      resection was possible in all patients. In 2 individuals (6.8%) the fistula
      recurred, but could be surgically treated using laparoscopic technique. In 1
      patient (3.4%) wound healing complications were observed. CONCLUSIONS: Clinical
      examination and ultrasound are generally sufficient for diagnosing persisting
      urachal fistula. Laparoscopic urachal fistula resection is a safe and effective
      technique and should thus be taken as a standard procedure.

PMID- 21857485
TI  - Editorial commentary.

PMID- 21857486
TI  - A novel technique to treat a major bile duct leak.

PMID- 21857487
TI  - Barrett esophagus after surgical treatment for achalasia.

PMID- 21857488
TI  - Laparoscopic approach for giant adrenal tumor.

PMID- 21857489
TI  - Inflammation predicts changes in high-density lipoprotein particles and
      apolipoprotein A1 following initiation of antiretroviral therapy.
AB  - BACKGROUND: The effects of HIV infection and antiretroviral therapy (ART) on
      usual lipid levels have been reported. The effects of initiating versus deferring
      ART on high-density and low-density lipoprotein particle (HDL-P and LDL-P,
      respectively) concentrations and apolipoprotein (Apo) levels are not well
      described. METHODS: In a subgroup of participants not taking ART at study entry
      who were randomized in the Strategies for Management of Antiretroviral Therapy
      (SMART) trial to immediately initiate ART ('viral suppression group') or to defer
      it ('drug conservation group'), lipoprotein particle concentrations and ApoA1 and
      ApoB levels were measured at baseline and at 2 and 6 months following
      randomization. RESULTS: Compared with drug conservation group (n = 126), HDL-P
      and ApoA1 levels increased among viral suppression participants (n = 128) after
      starting ART. At 6 months, viral suppression participants had 13% higher total
      HDL-P (P < 0.001) and 9% higher ApoA1 (P < 0.001). LDL-P, very low density
      lipoprotein particle, and ApoB did not differ significantly between the viral
      suppression and drug conservation groups. Among viral suppression participants,
      predictors of HDL-P and ApoA1 increases included baseline levels of high
      sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6), but not HIV RNA
      level, CD4 cell count, or traditional cardiovascular disease risk factors. The
      effect of starting ART on changes in HDL-P and ApoA1 was greater for those with
      higher versus lower baseline levels of IL-6 (P = 0.001 and 0.08, respectively,
      for interaction) or hsCRP (P = 0.01 and 0.04, respectively, for interaction).
      CONCLUSION: HDL-P and ApoA1 increase following ART initiation, to a degree that
      depends on the degree of inflammation present at entry. These findings suggest
      that activation of inflammatory pathways contribute to HIV-associated changes in
      HDL.

PMID- 21857491
TI  - Persistent decline in estimated but not measured glomerular filtration rate on
      tenofovir may reflect tubular rather than glomerular toxicity.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been associated with proximal
      renal tubulopathy and reduction in estimated glomerular filtration rate (eGFR),
      without accounting for the tubular secretion of creatinine. METHODS: A substudy
      was performed among 19 participants of a randomized 48-week trial, comparing
      continuing first-line zidovudine/lamivudine (ZDV/3TC) with switching to
      TDF/emtricitabine (FTC). GFR was measured with [(125)I]-iothalamate (mGFR) and
      effective renal plasma flow (ERPF) with [(131)I]-hippuran. eGFR and tubular
      effects were assessed using plasma and urine samples. RESULTS: Of the 19
      patients, 18 were men, 15 whites, mean (SD) age 46.0 (8.9) years, plasma HIV-1
      RNA less than 50 copies/ml in all. After 48 weeks, eGFR using Cockcroft-Gault
      equation and ERPF, but not mGFR, had significantly decreased, and urinary alpha1
      microglobulin/creatinine and microalbumin/creatinine significantly increased in
      patients on TDF. Although phosphate metabolism on TDF was affected at week 4,
      differences between groups disappeared during follow-up. CONCLUSION: Replacing
      ZDV/3TC with TDF/FTC in this limited sample of virologically suppressed HIV-1
      infected adults was associated with mild persistent tubular but not glomerular
      dysfunction over 48 weeks. The observed persistent decrease in Cockcroft-Gault
      based eGFR, but not mGFR, rather than being indicative of glomerular dysfunction
      may be explained by TDF inhibiting tubular creatinine excretion.

PMID- 21857492
TI  - Alarming incidence of hepatitis C virus re-infection after treatment of sexually
      acquired acute hepatitis C virus infection in HIV-infected MSM.
AB  - BACKGROUND: Recent data indicate that seroprevalence of sexually transmitted
      hepatitis C virus (HCV) infection among MSM is stabilizing in Amsterdam. However,
      little is known about the incidence of HCV re-infection in MSM who have cleared
      their HCV infection. We, therefore, studied the incidence of re-infection in HIV
      infected MSM who were HCV RNA-negative following HCV treatment of acute primary
      infection. METHODS: Our study population comprised HIV-infected MSM at two large
      HIV outpatient clinics in Amsterdam, who were previously diagnosed with a
      sexually transmitted acute HCV infection and tested HCV RNA-negative at the end
      of treatment. We defined HCV re-infection as detectable HCV RNA in individuals
      with an undetectable HCV RNA at the end of treatment accompanied by a switch in
      HCV genotype or clade. Person-time methods were used to calculate the incidence
      of re-infection. RESULTS: Fifty-six persons who became HCV RNA-negative during
      primary acute HCV treatment were included. Five of the 56 cases relapsed and were
      not analysed. Eleven persons were re-infected. The incidence of HCV re-infection
      in this group was 15.2 per 100 person-years (95% confidence interval 8.0-26.5).
      The cumulative incidence was 33% within 2 years. DISCUSSION: An alarmingly high
      incidence of HCV re-infection was found in this group. This high re-infection
      rate indicates that current prevention measures should be discussed, frequent HCV
      RNA testing should be continued after successful treatment and, in case of
      possible relapse, clade typing should be performed to exclude re-infection.

PMID- 21857493
TI  - Hepatitis delta in HIV-infected individuals in Europe.
AB  - BACKGROUND: Hepatitis delta virus (HDV) infection results in the most aggressive
      form of chronic viral hepatitis. There is scarce information about the
      prevalence, epidemiology, virological profile and natural history of hepatitis
      delta in HIV patients. METHODS: From 16,597 HIV patients enrolled in EuroSIDA,
      1319 (7.9%) have ever reported serum hepatitis B virus (HBV) surface antigen
      (HBsAg)-positive. At last follow-up, 1084 (6.5%) patients were HBsAg-positive.
      The HDV substudy was carried out in 422 individuals for whom stored sera were
      available at the time they were HBsAg-positive. Anti-HDV immunoglobulin G was
      assessed using a commercial enzyme immunoassay (EIA) and serum HDV-RNA was
      quantified using a real-time PCR method. RESULTS: A total of 61 of 422 HBsAg
      positive carriers were anti-HDV-positive (prevalence: 14.5%). Hepatitis delta
      predominated in intravenous drug users and for this reason in south and/or east
      Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV-positive patients,
      with a median titer of 1.76*10(7) copies/ml. Overall, delta hepatitis patients
      showed lower serum HBV-DNA than the rest of HBsAg-positive carriers, although the
      inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D
      patients. Whereas HDV was not associated with progression to AIDS, it
      significantly influenced the risk of death. CONCLUSION: The prevalence of anti
      HDV in chronic HBsAg-positive/HIV carriers in EuroSIDA is 14.5%. Most of these
      patients exhibit detectable HDV viraemia. Viral interference between HBV and HDV
      is manifested in all but HBV genotype D carriers in whom overt coreplication of
      both viruses occurs which might result in enhanced liver damage. Overall, delta
      hepatitis increases the risk of liver-related deaths and overall mortality in HIV
      patients.

PMID- 21857490
TI  - Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir
      in treatment-naive HIV-1-infected patients (ACTG A5262).
AB  - OBJECTIVE: To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL)
      combination therapy in antiretroviral-naive patients. DESIGN: Phase IIb, single
      arm, open-label, multicenter study. METHODS: One hundred and twelve
      antiretroviral-naive, HIV-1-infected patients received DRV/r 800/100 mg once
      daily and RAL 400 mg twice daily. Primary endpoint was virologic failure by week
      24. Virologic failure was defined as confirmed viral load of 1000 copies/ml or
      more at week 12, or an increase of more than 0.5 log(10) copies/ml in viral load
      from week 4 to 12, or a confirmed viral load of more than 50 copies/ml at or
      after week 24. Protease and integrase genes were sequenced in patients
      experiencing virologic failure. RESULTS: Virologic failure rate was 16% [95%
      confidence interval (CI) 10-24] by week 24 and 26% (95% CI 19-36) by week 48 in
      an intent-to-treat analysis. Viral load at virologic failure was 51-200 copies/ml
      in 17/28 failures. Adjusting for age and sex, virologic failure was associated
      with baseline viral load of more than 100,000 copies/ml [hazard ratio 3.76, 95%
      CI (1.52-9.31), P = 0.004] and lower CD4 cell count [0.77 per 100 cells/MUl
      increase (95% CI 0.61-0.98), P = 0.037]. When trough RAL concentrations were
      included as a time-varying covariate in the analysis, virologic failure remained
      associated with baseline viral load more than 100,000 copies/ml [hazard ratio =
      4.67 (95% CI 1.93-11.25), P < 0.001], whereas RAL level below detection limit in
      plasma at one or more previous visits was associated with increased hazard
      [hazard ratio = 3.42 (95% CI 1.41-8.26), P = 0.006]. All five participants with
      integrase mutations during virologic failure had baseline viral load more than
      100,000 copies/ml. CONCLUSION: DRV/r plus RAL was effective and well tolerated in
      most patients, but virologic failure and integrase resistance were common,
      particularly in patients with baseline viral load more than 100,000 copies/ml.

PMID- 21857494
TI  - A novel role for Slit2/Robo1 axis in modulating HIV-1 replication in T cells.
AB  - OBJECTIVE: Slit2 is a secreted glycoprotein that has been shown to possess anti
      inflammatory properties. In addition, Slit2 has been shown to modulate CXCR4
      mediated functional effects in T cells. However, its role in HIV-1 pathogenesis
      is not known. The objective of the current study is to analyze the role of Slit2
      in modulating HIV-1 replication in T cells. METHODS: The effect of endogenous
      Slit2 expression of HIV-1 replication in T cells was studied by transient
      overexpression or downregulation of Slit2. The role of exogenous Slit2 was
      studied by analyzing the effect of soluble Slit2 protein on HIV-1 replication in
      T-cell lines and peripheral blood mononuclear cells (PBMCs). RESULTS: Studies on
      T-cell lines revealed a higher expression of Slit2 in Jurkat T cells compared
      with MT4 cells. We observed that downregulation of Slit2 in Jurkat T cells using
      Slit2-specific small inhibitor RNA enhanced HIV-1 replication. However,
      overexpression of Slit2 in MT4 cells and PBMCs reduced HIV-1 replication. As
      Slit2 is a secretory protein, we further analyzed the role of soluble Slit2 on
      HIV-1 virus replication using various cell lines and PBMCs. Our data indicated
      that exogenous Slit2 inhibited replication of both X4-tropic and R5-tropic HIV-1
      viruses. Further studies revealed that Slit2 mediated its functional effects by
      binding to Robo1 receptor. CONCLUSION: Taken together, our results describe
      Slit2/Robo1 axis as a novel modulator of HIV-1 replication in T cells. These
      studies may contribute to the understanding of the immunopathogenesis of HIV-1
      infection.

PMID- 21857496
TI  - What is FAER? The Foundation for Anesthesia Education and Research.

PMID- 21857498
TI  - An Australasian perspective in supporting researchers in anesthesia and intensive
      care.

PMID- 21857497
TI  - Human Alzheimer and inflammation biomarkers after anesthesia and surgery.
AB  - BACKGROUND: The prevalence of postoperative cognitive disturbance, coupled with
      growing in vitro, cell, and animal evidence suggesting anesthetic effects on
      neurodegeneration, calls for additional study of the interaction between surgical
      care and Alzheimer neuropathology. The authors studied human cerebrospinal fluid
      (CSF) biomarkers during surgery. METHODS: Eleven patients undergoing idiopathic
      nasal CSF leak correction were admitted to this Institutional Review Board
      approved study. Lumbar subarachnoid catheters were placed before the procedure.
      Anesthesia was total intravenous propofol or remifentanil or inhalational
      sevoflurane, depending on provider choice. CSF samples were taken after catheter
      placement (base), at procedure end (0 h), and then at 6, 24, and 48 h. CSF was
      analyzed using xMAP Luminex immunoassay (Luminex, Austin, TX). RESULTS: Of the 11
      patients (age range, 53 +/- 6 yr), 8 were women; 4 received intravenous
      anesthesia, 6 sevoflurane, and 1 mixed. Procedures lasted 6.4 +/- 2 h. Mean CSF
      amyloid-beta(1-42) remained unchanged, but total-tau and phosphorylated-tau181P
      increased progressively until at least 48 h. Total-tau, phosphorylated-tau, or
      amyloid-beta(1-42) concentrations were not different between anesthetic groups.
      CSF interleukin-10, S100Beta, and tumor necrosis factor alpha were increased
      similarly in both anesthetic groups at 24 h, but interleukin-6 was increased more
      in the inhalational group. CONCLUSION: These data indicate a robust
      neuroinflammatory response, including not only the usual markers (interleukin-6,
      tumor necrosis factor alpha, interleukin-10), but also S100Beta and tau, markers
      of injury. The total-tau/amyloid-beta(1-42) ratio increased in a pattern
      consistent with Alzheimer disease, largely because of an increase in total-tau
      rather than a decline in amyloid-beta(1-42). The differences in CSF interleukin-6
      concentrations suggest that anesthetic management may make a difference in
      neuroinflammatory response.

PMID- 21857495
TI  - A plasma microRNA signature of acute lentiviral infection:  biomarkers of central
      nervous system disease.
AB  - OBJECTIVE: Plasma microRNAs (miRNAs) are modulated during disease and are
      emerging biomarkers; they have not been characterized in HIV infection. Using our
      macaque/simian immunodeficiency virus (SIV) model of HIV, we sought to identify a
      plasma miRNA profile of acute lentiviral infection, evaluate its relationship
      with known cellular and viral determinants of lentivirus-associated central
      nervous system (CNS) disease, and explore the potential of miRNAs to predict CNS
      disease. DESIGN: Plasma samples were obtained before inoculation and 10 days
      after inoculation from SIV-infected macaques. METHODS: Plasma miRNA expression
      profiles were determined by TaqMan low-density array for six individuals. miRNA
      expression was compared with levels of cytokines, virus, and plasma platelet
      count. miRNA results were confirmed by single miRNA-specific assays for 10
      macaques. Nineteen individuals were used to validate a disease prediction test.
      RESULTS: A 45-miRNA signature of acute infection (differential expression with P
      < 0.05 after multiple comparison correction) classified plasma as infected or
      not. Several differentially expressed miRNAs correlated with CNS disease
      associated cytokines interleukin-6 and CCL2 and included predicted and/or
      validated regulators of the corresponding mRNAs. miRNAs tracked with viral load
      and platelet count were also predictors of CNS disease. At least six miRNAs were
      significantly differentially expressed in individuals with severe versus no CNS
      disease; in an unweighted expression test, they predicted CNS disease.
      CONCLUSION: Acute-phase differential expression of plasma miRNAs predicts CNS
      disease and suggests that CNS damage or predisposition to disease progression
      begins in the earliest phase of infection. Plasma miRNAs should be investigated
      further as leading indicators of HIV diseases as early as acute infection.

PMID- 21857499
TI  - Europe is mostly united but lacks a common support of young investigators.

PMID- 21857501
TI  - Autopsy and malpractice considerations.

PMID- 21857502
TI  - Methyl-beta-cyclodextrin induces programmed cell death in chronic myeloid
      leukemia cells and, combined with imatinib, produces a synergistic downregulation
      of ERK/SPK1 signaling.
AB  - Lipid rafts mediate several survival signals in the development of chronic
      myeloid leukemia (CML). Methyl-beta-cyclodextrin (MbetaCD) is an inhibitor
      specifically designed to disrupt lipid rafts in cells by depleting the
      cholesterol component. We hypothesize that treatment of CML cells with MbetaCD
      and imatinib could reduce imatinib resistance. Apoptotic and autophagic cell
      death was assayed using annexin V-propidium iodide double staining,
      immunoblotting, and immunocytochemistry. We next investigated whether MbetaCD
      could enhance the cytotoxicity of imatinib in imatinib-sensitive and imatinib
      resistant K562 cells. Extracellular signal-regulated kinase/sphingosine kinase 1
      signaling downstream of lipid raft-activated signaling pathways was significantly
      inhibited by treatment of cells with a combination of MbetaCD and imatinib
      compared with treatment with either agent alone. MbetaCD induces programmed cell
      death in CML cells, and its antileukemia action is synergistic with that of
      imatinib.

PMID- 21857500
TI  - Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep
      regulating brain regions of Sprague Dawley rat.
AB  - BACKGROUND: Buprenorphine, a partial MU-opioid receptor agonist and kappa-opioid
      receptor antagonist, is an effective analgesic. The effects of buprenorphine on
      sleep have not been well characterized. This study tested the hypothesis that an
      antinociceptive dose of buprenorphine decreases sleep and decreases adenosine
      concentrations in regions of the basal forebrain and pontine brainstem that
      regulate sleep. METHODS: Male Sprague Dawley rats were implanted with intravenous
      catheters and electrodes for recording states of wakefulness and sleep.
      Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter
      and sleep-wake states were recorded for 24 h. In additional rats, buprenorphine
      was delivered by microdialysis to the pontine reticular formation and substantia
      innominata of the basal forebrain while adenosine was simultaneously measured.
      RESULTS: An antinociceptive dose of buprenorphine caused a significant increase
      in wakefulness (25.2%) and a decrease in nonrapid eye movement sleep (-22.1%) and
      rapid eye movement sleep (-3.1%). Buprenorphine also increased
      electroencephalographic delta power during nonrapid eye movement sleep.
      Coadministration of the sedative-hypnotic eszopiclone diminished the
      buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine
      significantly decreased adenosine concentrations in the pontine reticular
      formation (-14.6%) and substantia innominata (-36.7%). Intravenous administration
      of buprenorphine significantly decreased (-20%) adenosine in the substantia
      innominata. CONCLUSIONS: Buprenorphine significantly increased time spent awake,
      decreased nonrapid eye movement sleep, and increased latency to sleep onset.
      These disruptions in sleep architecture were mitigated by coadministration of the
      nonbenzodiazepine sedative-hypnotic eszopiclone. The buprenorphine-induced
      decrease in adenosine concentrations in basal forebrain and pontine reticular
      formation is consistent with the interpretation that decreasing adenosine in
      sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.

PMID- 21857503
TI  - Comparison of two vascular-disrupting agents at a clinically relevant dose in
      rodent liver tumors with multiparametric magnetic resonance imaging biomarkers.
AB  - We sought to compare the therapeutic efficacy between two vascular-disrupting
      agents, combretastatin A4 phosphate (CA4P) and ZD6126, at a clinically relevant
      dose on tumor models with magnetic resonance imaging (MRI). Thirty rats with
      liver rhabdomyosarcoma were randomized into CA4P (10 mg/kg), ZD6126 (10 mg/kg),
      and control group (n=10 for each group). Multiparametric MRI biomarkers including
      tumor volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient
      (ADC), and K (volume transfer constant) derived from T2-weighted, T1-weighted,
      contrast-enhanced T1-weighted, and diffusion-weighted imaging, and dynamic
      contrast-enhanced MRI were compared at pretreatment, 1 h, 6 h, 24 h, 48 h, and
      120 h posttreatment; they were validated using ex-vivo techniques. Relative to
      rapidly growing tumors without necrosis in control rats, tumors grew slower in
      the CA4P group compared with the ZD6126 group with a higher necrosis ratio at 120
      h (P<0.05), as proven by histopathology. In the CA4P group, K decreased from 1 h
      until 6 h, and partially recovered at 120 h. In the ZD6126 group, the reduced K
      at 1 h began to rebound from 6 h and exceeded the baseline value at 120 h
      (P<0.05), parallel to evolving enhancement ratios (P<0.05). ADC revealed more
      necrotic tumors with CA4P versus ZD6126 at 120 h (P<0.05). The different tumor
      responses were confirmed by ex-vivo microangiography and histopathology. CA4P was
      more effective than ZD6126 in impairing blood supply, inducing necrosis, and
      delaying growth in rat liver tumors at a clinically relevant dose. A single dose
      of vascular-disrupting agent was insufficient to destroy the tumor. The
      multiparametric MRI biomarkers enabled in-vivo noninvasive comparison of
      therapeutic efficacy between CA4P and ZD6126.

PMID- 21857504
TI  - The relation between health literacy, hypertension knowledge, and blood pressure
      among middle-aged Japanese adults.
AB  - BACKGROUND: With the growth in the popularity of the Internet, individuals'
      skills in finding and applying information about health issues [health literacy
      (HL)] are affecting their health behaviors. This study aimed to examine
      functional HL (FHL), critical HL (CHL), and hypertension knowledge (HK) among
      middle-aged Japanese adults. In addition, to measure health outcomes, we examined
      the relationship between HL, HK, and blood pressure (BP) level. METHODS: The
      study included middle-aged participants who received an annual health check-up at
      an urban clinic in Japan. FHL, CHL, and HK were assessed using structured
      questionnaires. In addition, BP was obtained from the electronic medical record.
      RESULTS: Participants included 139 women and 181 men with a mean age of 54.4
      years (standard deviation = 0.69). Individuals with lower reading comprehension
      scores in FHL were more likely to have a history of hypertension (P = 0.003) and
      diabetes mellitus (P = 0.02). Individuals with lower CHL had significantly higher
      rates of current smoking (P = 0.03) and men with lower CHL had a significantly
      higher waist circumference (P = 0.03). There was a significant relationship
      between sex and HK (P = 0.03). Systolic BP in women with higher HL and HK was
      significantly lower than in men with higher FHL (P < 0.001), CHL (P = 0.01), and
      HK (P = 0.001). CONCLUSION: Lower HL and HK were associated with a poor health
      status and BP level in middle-aged participants. Further research is needed to
      examine the role of health management in improving outcomes and to address
      disparities between individuals with higher and lower HL.

PMID- 21857505
TI  - Trisomy 14 mosaicism:  clinical and cytogenetic findings in an adult.
AB  - Trisomy 14 mosaicism is a well-known but rare chromosomal defect with most
      frequently reported features being growth retardation, psychomotor retardation,
      broad nose, dysplastic and/or apparently low set ears, micrognathia, short neck,
      congenital heart disease and, in males, micropenis and cryptorchidism. Other
      frequent findings are prominent forehead, hyperteleorism, narrow palpebral
      fissures, large mouth, cleft or highly arched palate, body asymmetry and abnormal
      skin-pigmentation (Fujimoto et al., 1992). To the best of our knowledge, only one
      adult patient with trisomy 14 mosaicism has been described so far (Fujimoto et
      al., 1992). We present the clinical findings in a 27-year-old woman to add to the
      knowledge of the adult phenotype of trisomy 14 mosaicism and to demonstrate the
      findings on fibroblast culture.

PMID- 21857506
TI  - Effects of Ramadan intermittent fasting on middle-distance running performance in
      well-trained runners.
AB  - OBJECTIVE: To assess whether Ramadan intermittent fasting (RIF) affects 5000-m
      running performance and physiological parameters classically associated with
      middle-distance performance. DESIGN: Two experimental groups (Ramadan fasting, n
      = 9, vs control, n = 9) participated in 2 experimental sessions, one before RIF
      and the other at the last week of fasting. SETTING: For each session, subjects
      completed 4 tests in the same order: a maximal running test, a maximal voluntary
      contraction (MVC) of knee extensor, 2 rectangular submaximal exercises on
      treadmill for 6 minutes at an intensity corresponding to the first ventilatory
      threshold (VT1), and a running performance test (5000 m). PARTICIPANTS: Eighteen,
      well-trained, middle-distance runners. MAIN OUTCOME MEASURES: Maximal oxygen
      consumption, MVC, running performance, running efficiency, submaximal VO(2)
      kinetics parameters (VO(2), VO(2)b, time constant tau, and amplitude A1) and
      anthropometric parameters were recorded or calculated. RESULTS: At the end of
      Ramadan fasting, a decrease in MVC was observed (-3.2%; P < 0.00001; eta, 0.80),
      associated with an increase in the time constant of oxygen kinetics (+51%; P <
      0.00007; eta, 0.72) and a decrease in performance (-5%; P < 0.0007; eta, 0.51).
      No effect was observed on running efficiency or maximal aerobic power.
      CONCLUSIONS: These results suggest that Ramadan changes in muscular performance
      and oxygen kinetics could affect performance during middle-distance events and
      need to be considered to choose training protocols during RIF.

PMID- 21857507
TI  - Management of nontraumatic corneal perforation with tectonic drape patch and
      cyanoacrylate glue.

PMID- 21857508
TI  - Angiographic patterns of myocardial reperfusion after primary angioplasty and
      ventricular remodeling.
AB  - BACKGROUND: No reflow after primary percutaneous coronary intervention is a
      dynamic process and its reversibility may affect left ventricular (LV)
      remodeling. We aimed at assessing in-hospital evolution of angiographic no
      reflow, predictors of its reversibility, and its impact on LV function at follow
      up (FU). METHODS: Fifty-three consecutive patients (age, 60+/-10 years; male sex,
      79%) presenting with ST-elevation myocardial infarction and undergoing primary
      percutaneous coronary intervention within 12 h of symptom onset were enrolled. No
      reflow was defined as a final thrombolysis in myocardial infarction (TIMI) flow
      of 2 or final TIMI flow of 3 with myocardial blush grade (MBG) of less than 2.
      The evolution of angiographic no reflow was assessed by repeat in-hospital
      coronary angiography. Patients with no reflow found to have an improvement of
      TIMI and/or MBG leading to a final TIMI 3 and MBG of greater than or equal to 2
      were classified as reversible no reflow; the remaining patients were classified
      as sustained no reflow. Variables predicting the patterns of no reflow, recorded
      on admission, were assessed among clinical, angiographic and laboratory data. FU
      echocardiographic data (at 6 months) were compared with those obtained in
      hospital according to no reflow evolution. RESULTS: Thirty-six patients (68%)
      exhibited myocardial reperfusion; 17 patients (32%) showed no reflow. Among
      these, six patients (age, 58+/-10 years; male sex, 83%) showed sustained no
      reflow, whereas 11 patients (age, 55+/-8 years; male sex, 82%) showed reversible
      no reflow. Patients with sustained no reflow had longer time to percutaneous
      coronary intervention (261+/-80 min) compared with those with myocardial
      reperfusion (216+/-94 min) or reversible no reflow (237+/-76 min; P=0.008 and
      0.05, respectively). Moreover, patients with sustained no reflow had a higher
      peak troponin-T levels (14.5 ng/ml; range, 7.5-20.2 ng/ml) compared with those
      presenting with myocardial reperfusion (3.9 ng/ml; range, 3.3-9.1 ng/ml) and
      reversible no reflow (7.7 ng/ml; range, 3.6-29.9 ng/ml; P=0.03 and 0.07,
      respectively). At multivariate ordinal logistic regression, time pre-PCI retained
      its statistical significant association with angiographic no reflow evolution
      (odds ratio=2.54; 95% confidence interval: 1.45-6.53; P=0.04), with troponin T
      levels showing a borderline statistical significance (odds ratio=3.12; 95%
      confidence interval: 1.07-6.23; P=0.09). Finally, in patients with sustained no
      reflow only both end-diastolic and end-systolic volumes significantly increased
      at FU (P<0.001 and 0.001, respectively). CONCLUSION: Sustained no reflow is
      associated with a longer ischemic time and predicts worse LV remodeling. No
      reflow, however, shows an in-hospital reversibility calling for therapeutic
      interventions when its prevention fails.

PMID- 21857509
TI  - Physiological correlates of densely calcified coronary lesions on coronary
      computed tomography angiography among patients with low-to-intermediate coronary
      artery disease likelihood.
AB  - OBJECTIVES: Coronary computed tomography angiography (CCTA) is often used to
      assess the extent and severity of atherosclerosis. A major limitation of CCTA are
      densely calcified coronary plaques that obscure the underlying lumen rendering
      assessment difficult. The purpose of this study was to evaluate the hemodynamic
      importance of densely calcified coronary lesions on CCTA in patients with low-to
      intermediate likelihood of coronary artery disease. METHODS: We studied 92
      patients (64+/-10 years, 75% men) who underwent CCTA and stress perfusion
      cardiovascular magnetic resonance (CMR). Coronary stenoses were categorized as
      none, less than 50%, 50-70%, and greater than 70%, or densely calcified. Coronary
      arteries were considered densely calcified if the artery had a calcified lesion
      obscuring the underlying lumen and did not have another stenosis of greater than
      50%. CMR was considered abnormal if there was reversible ischemia or myocardial
      scar determined by the presence of late gadolinium enhancement. RESULTS: Among
      the 92 patients, 271 vessels were analyzed of which 44 (16%) were considered
      densely calcified. Among these 44 coronary territories, six (14%) had abnormal
      CMR findings. On a per-vessel analysis, a proportional increase in the number of
      myocardial segments with reversible ischemia or the presence of late gadolinium
      enhancement was associated with an increase of CCTA stenosis ranging from 2% in
      patients without coronary plaque to 70% in patients with a greater than 70%
      stenosis (P<0.0001). CONCLUSION: In conclusion, the vast majority (86%) of
      densely calcified lesions were not hemodynamically significant in our study. As
      our study was in patients with relatively low-to-intermediate likelihood of
      coronary artery disease, a prospective study is warranted to assess if our
      findings are generalizable to other patient populations.

PMID- 21857510
TI  - New approaches to the treatment of giardiasis.
AB  - PURPOSE OF REVIEW: Giardiasis is one of the most common causes of diarrheal
      disease worldwide, yet existing antimicrobial therapies are not always effective
      and drug resistance occurs in vivo and in vitro. The review focuses on recent
      advances in the development of new antigiardial drug candidates. RECENT FINDINGS:
      Modification of existing drug leads is a major strategy to develop new high
      potency drugs. Complex derivatives of 5-nitroimidazole, the core structure of the
      most commonly used antigiardial drug, metronidazole, have shown significantly
      improved activities against Giardia and the ability to overcome metronidazole
      resistance. Derivatives of benzimidazole, the structural core of the effective
      antigiardial albendazole, are also exhibiting promising new activities. Beyond
      lead modifications, several new classes of antigiardial drug candidates have
      recently been identified by high-throughput screening of large compound
      libraries, and first efforts have been reported on the development of drugs
      tailored to known molecular targets in Giardia. SUMMARY: The pipeline of new
      antigiardial drug candidates has significantly expanded over the last few years,
      but this expansion has so far not been accompanied by demonstration of efficacy
      in animal models or by a clear understanding of the action mechanisms,
      particularly in regard to new nitro antimicrobials. Many challenges are still to
      be expected before clinical utility of new antigiardial drugs can be established.

PMID- 21857512
TI  - Update in treatment of Chagas disease.
AB  - PURPOSE OF REVIEW: This review discusses the recent data about the pathogenesis
      of Chagas disease, tolerance of drugs, and follow-up of patients impacting the
      treatment of Chagas disease in immunocompetent and immunocompromised patients.
      RECENT FINDINGS: The role of the parasite to promote direct or indirect organ
      damage in the chronic phase of the disease as well as the usefulness of
      antiparasitic treatment to slow or prevent the deterioration of cardiac function
      and the aggravation of Chagasic cardiomyopathy lead to an extension of the
      indications of treatment. Tolerance is poor for the two drugs, benznidazole and
      nifurtimox. The rates of adverse events and treatment discontinuation before 60
      days are higher with nifurtimox. PCR, and in the near future immunologic tests,
      might allow assessment of the early success or failure of the antiparasitic
      treatment. SUMMARY: Assessment of alternative drugs, such as posaconazole, and of
      new strategies of treatment (combination of two antiparasitic drugs, association
      of antiparasitic and immunomodulatory drugs, and re-treatment), and follow-up are
      a global health priority.

PMID- 21857511
TI  - Enteropathogenic escherichia coli infection in children.
AB  - PURPOSE OF REVIEW: Enteropathogenic Escherichia coli (EPEC) is an important
      diarrheal pathogen of young children. As the diagnosis of EPEC is now based
      mainly on molecular criteria, there has been an important change in its
      prevalence. The purpose of this study is to review the current epidemiology of
      EPEC infection and the new insights into its physiopathology. RECENT FINDINGS:
      Recent epidemiological studies indicate that atypical EPEC (aEPEC) is more
      prevalent than typical EPEC (tEPEC) in both developed and developing countries,
      and that aEPEC is important in both pediatric endemic diarrhea and diarrhea
      outbreaks. Therefore, it is important to further characterize the pathogenicity
      of these emerging strains. The virulence mechanisms and physiopathology of the
      attaching and effacing lesion (A/E) and the type three secretion-system (T3SS)
      are complex but well studied. A/E strains use their pool of locus of enterocyte
      effacement (LEE)-encoded and non-LEE-encoded effector proteins to subvert and
      modulate cellular and barrier properties of the host. However, the exact
      mechanisms of diarrhea in EPEC infection are not completely understood. SUMMARY:
      Remarkable progress has been made to identify virulence determinants required to
      mediate the pathogenesis of EPEC. However, fast, easy, and inexpensive diagnostic
      methods are needed in order to define optimal treatment and prevention for
      children in endemic areas.

PMID- 21857513
TI  - Surgery of malignant gliomas:  advances and perspectives.
AB  - PURPOSE OF REVIEW: One of the most controversial issues in the combined treatment
      of malignant gliomas is the role of surgical resection, even though the relevance
      of surgery in obtaining tissue diagnosis and alleviating clinical symptoms is
      well defined; more debated is the importance of radical surgery in improving the
      patient final outcome. This review aims to present an overview of the
      recommendations for surgical treatment of malignant gliomas, and to describe the
      potential role of locoregional treatments. RECENT FINDINGS: An increasing series
      of data are being collected in favour of radical surgical removal, with the
      support of intraoperative imaging and fluorescence guide. More controversial, but
      theoretically relevant, are the experiences of locoregional treatments, mainly in
      the contest of present combined modality treatments; different interesting
      approaches are being studied, without any significant therapeutical advantage in
      phase III studies, and only biodegradable carmustine wafers entered in the
      clinical practice. SUMMARY: The gold standard of surgical treatment of malignant
      gliomas has to include well tolerated and radical tumour removal, taking
      advantage of the introduction of new technological tools. The future role of
      neurosurgical treatment of malignant glioma is linked to intratumoural
      administration of antiblastic agents and the development of more efficient
      delivery systems; localized therapies have to be considered in a well defined
      multistep therapeutic strategy.

PMID- 21857514
TI  - Extracorporeal lung perfusion.
AB  - PURPOSE OF REVIEW: The number of patients listed for lung transplantation largely
      exceeds the number of available transplantable organs because of both a shortage
      of organ donors and a low utilization rate of lungs from those donors due to
      injuries acquired during the process of brain death and intensive care unit (ICU)
      care. A novel strategy for donor lung preservation - ex-vivo lung perfusion
      (EVLP) - that keeps the organ at physiological protective conditions has shown
      great promise to increase lung utilization by reassessing, treating, and
      repairing injured donor lungs prior to transplantation. RECENT FINDINGS: A first
      clinical trial using EVLP has shown the method to be safe and to allow for
      reassessment and improvement in function of lungs from high-risk donor lungs
      prior to transplantation. When these lungs were transplanted, low rates of
      primary graft dysfunction were achieved, and the early outcomes were similar to
      those with conventionally selected and transplanted lungs. Preclinical studies
      have shown a great potential of EVLP as a platform for the delivery of novel
      simple and advanced therapies to repair injured organs ex vivo and thus further
      increase the donor lung utilization rate. SUMMARY: EVLP triggers a new era in
      lung transplantation. This method will allow for more and better organs to become
      available. Several experimental studies, clinical case reports, and a clinical
      trial have shown the safety of EVLP and the numerous potentials of EVLP.

PMID- 21857515
TI  - Donation after cardiac death in pediatric organ transplantation.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the history, current
      practice, and outcomes of the transplantation of organs donated after cardiac
      death (DCD) in children. RECENT FINDINGS: The rate of death on the waiting list
      is greater for children under 5 years of age than for any other age group. The
      organ shortage experienced by the general population awaiting transplantation is
      made more complex due to the need for size-appropriate organs for transplantation
      into small children. Pediatric DCD organ recovery has been proposed as a means of
      ameliorating this shortage. SUMMARY: The use of DCD organs has experienced
      resurgence in the past 15 years, and a growing body of literature supports their
      use in selected cases. Recent experience in pediatric transplantation using DCD
      heart, lung, liver, and kidney is reviewed.

PMID- 21857516
TI  - Comparison of ear-canal reflectance and umbo velocity in patients with conductive
      hearing loss: a preliminary study.
AB  - OBJECTIVE: The goal of the present study was to investigate the clinical utility
      of measurements of ear-canal reflectance (ECR) in a population of patients with
      conductive hearing loss in the presence of an intact, healthy tympanic membrane
      and an aerated middle ear. We also sought to compare the diagnostic accuracy of
      umbo velocity (VU) measurements and measurements of ECR in the same group of
      patients. DESIGN: This prospective study comprised 31 adult patients with
      conductive hearing loss, of which 14 had surgically confirmed stapes fixation due
      to otosclerosis, 6 had surgically confirmed ossicular discontinuity, and 11 had
      computed tomography and vestibular evoked myogenic potential confirmed superior
      semicircular canal dehiscence (SCD). Measurements on all 31 ears included pure
      tone audiometry for 0.25 to 8 kHz, ECR for 0.2 to 6 kHz using the Mimosa
      Acoustics HearID system, and VU for 0.3 to 6 kHz using the HLV-1000 laser Doppler
      vibrometer (Polytec Inc, Waldbronn, Germany). We analyzed power reflectance |ECR|
      as well as the absorbance level = 10 * log10(1 - |ECR|). All measurements were
      made before any surgical intervention. The VU and ECR data were plotted against
      normative data obtained in a companion study of 58 strictly defined normal ears
      (). RESULTS: Small increases in |ECR| at low-to-mid frequencies (400-1000 Hz)
      were observed in cases with stapes fixation, while narrowband decreases were seen
      for both SCD and ossicular discontinuity. The SCD and ossicular discontinuity
      differed in that the SCD had smaller decreases at mid-frequency (~1000 Hz),
      whereas ossicular discontinuity had larger decreases at lower frequencies (500
      800 Hz). SCD tended to have less air-bone gap at high frequencies (1-4 kHz)
      compared with stapes fixation and ossicular discontinuity. The |ECR|
      measurements, in conjunction with audiometry, could successfully separate 28 of
      the 31 cases into the three pathologies. By comparison, VU measurements, in
      conjunction with audiometry, could successfully separate various pathologies in
      29 of 31 cases. CONCLUSIONS: The combination of |ECR| with audiometry showed
      clinical utility in the differential diagnosis of conductive hearing loss in the
      presence of an intact tympanic membrane and an aerated middle ear and seems to be
      of similar sensitivity and specificity to measurements of VU plus audiometry.
      Additional research is needed to expand upon these promising preliminary results.

PMID- 21857517
TI  - Ear-canal reflectance, umbo velocity, and tympanometry in normal-hearing adults.
AB  - OBJECTIVE: This study compares measurements of ear-canal reflectance (ECR) to
      other objective measurements of middle ear function including audiometry, umbo
      velocity (VU), and tympanometry in a population of strictly defined normal
      hearing ears. DESIGN: Data were prospectively gathered from 58 ears of 29 normal
      hearing subjects, 16 females and 13 males, aged 22 to 64 yr. Subjects met all of
      the following criteria to be considered as having normal hearing: (1) no history
      of significant middle ear disease; (2) no history of otologic surgery; (3) normal
      tympanic membrane on otoscopy; (4) pure-tone audiometric thresholds of 20 dB HL
      or better for 0.25 to 8 kHz; (5) air-bone gaps no greater than 15 dB at 0.25 kHz
      and 10 dB for 0.5 to 4 kHz; (6) normal, type-A peaked tympanograms; and (7) all
      subjects had two "normal" ears (as defined by these criteria). Measurements
      included pure-tone audiometry for 0.25 to 8 kHz, standard 226 Hz tympanometry,
      ECR for 0.2 to 6 kHz at 60 dB SPL using the Mimosa Acoustics HearID system, and
      umbo velocity (VU) for 0.3 to 6 kHz at 70 to 90 dB SPL using the HLV-1000 laser
      Doppler vibrometer (Polytec Inc). RESULTS: Mean power reflectance (|ECR|) was
      near 1.0 at 0.2 to 0.3 kHz, decreased to a broad minimum of 0.3 to 0.4 between 1
      and 4 kHz, and then sharply increased to almost 0.8 by 6 kHz. The mean pressure
      reflectance phase angle (?ECR) plotted on a linear frequency scale showed a group
      delay of approximately 0.1 msec for 0.2 to 6 kHz. Small significant differences
      were observed in |ECR| at the lowest frequencies between right and left ears and
      between males and females at 4 kHz. |ECR| decreased with age but reached
      significance only at 1 kHz. Our ECR measurements were generally similar to
      previous published reports. Highly significant negative correlations were found
      between |ECR| and VU for frequencies below 1 kHz. Significant correlations were
      also found between the tympanometrically determined peak total compliance and
      |ECR| and VU at frequencies below 1 kHz. The results suggest that middle ear
      compliance contributes significantly to the measured power reflectance and umbo
      velocity at frequencies below 1 kHz but not at higher frequencies. CONCLUSIONS:
      This study has established a database of objective measurements of middle ear
      function (ECR, umbo velocity, tympanometry) in a population of strictly defined
      normal-hearing ears. These data will promote our understanding of normal middle
      ear function and will serve as a control for comparison to similar measurements
      made in pathological ears.

PMID- 21857518
TI  - Open gastrostomy under ultrasound-guided bilateral oblique subcostal transversus
      abdominis plane block:  a case series.

PMID- 21857520
TI  - Randomised comparison of hyperbaric articaine and hyperbaric low-dose bupivacaine
      along with fentanyl in spinal anaesthesia for day-case inguinal herniorrhaphy.
AB  - BACKGROUND AND OBJECTIVE: Low-dose mixture of hyperbaric bupivacaine and fentanyl
      is commonly used in day-case spinal anaesthesia. Using hyperbaric articaine, the
      onset may be faster and duration more predictable than with bupivacaine-fentanyl.
      We compared these two spinal anaesthetics for inguinal herniorrhaphy. METHODS:
      Adult patients were randomised to spinal anaesthesia with hyperbaric articaine 84
      mg (group A, n = 40) or hyperbaric bupivacaine 7 mg along with fentanyl 10 MUg
      (group B+F, n = 40). A blinded observer tested the block characteristics. Aiming
      at sensory block spread to T10 dermatome, the operating table was tilted head-end
      up or down 10 degrees  (once or twice), as required. Postoperative telephone
      interviews were performed. RESULTS: All patients in group A had a sensory block
      to T10 in a median time of 4 (range 2-20) min. In group B+F, the median onset
      time of T10 analgesia was 10 (2-30) min (P < 0.001), but T10 analgesia was not
      reached in seven of 40 B+F patients. A head-up tilt was needed in 37 of 40 group
      A patients to prevent from too extensive cephalad spread of block, and 34 of 40
      group B+F patients needed a head-down tilt to enhance cephalad spread of
      analgesia. To treat hypotension, 6.4 mg of ephedrine was required, on average, in
      group A and 1.8 = mg in group B+F (P = 0.01). Median time to recovery from
      sensory block was significantly shorter in group A (2.5 h) than in group B+F (3
      h; P = 0.002). General anaesthesia was needed in three patients (group A, two
      patients: sensory block too short; group B+F, one patient: sensory block too
      limited). CONCLUSION: Hyperbaric articaine leads to faster onset of block and
      faster recovery than bupivacaine along with fentanyl. Hypotension is more common
      with articaine. The onset and extension of the spinal block are unpredictable
      when using these techniques.

PMID- 21857521
TI  - Ginkgo may prevent genetic-associated ovarian cancer risk:  multiple biomarkers
      and anticancer pathways induced by ginkgolide B in BRCA1-mutant ovarian
      epithelial cells.
AB  - Women carrying BRCA1 mutations have a higher risk of developing ovarian cancers.
      Options to reduce this risk are largely limited to prophylactic surgery, which
      leads to a decrease in the quality of life and permanently damages fertility.
      There is a obvious and an urgent need to identify a noninvasive approach to
      effectively prevent the ovarian cancer risk, specifically for those women of
      reproductive age. Our previous studies showed that the use of the herbal remedy
      Ginkgo biloba may reduce the risk for nonmucinous ovarian cancer. Here, we
      explored whether Ginkgo biloba might also be an effective agent to reduce BRCA1
      associated ovarian cancer (always serous-type) risk. A human ovarian surface
      epithelial cell line-636 was developed from a BRCA1-mutant carrier. Cells were
      treated with ginkgolide B (GB) or dimethyl sulfoxide, and protein lysates from
      the cells were applied to antibody microarrays to determine upregulated or
      downregulated protein expression patterns. Anticancer activities and the
      associated networking pathways with the altered proteins were analyzed by using
      the Pathway Studio software. After GB treatment, 28 proteins were shown to be
      consistently upregulated (1.5-15.5-fold), and 22 proteins were downregulated (1.5
      28.3-fold). Bioinformatics software analysis indicated that multiple mechanisms
      and signal pathways are involved in anticancer activities in BRCA1-mutant cells
      induced by GB treatment. These pathways include cell proliferation, tumor
      suppression, and DNA damage repair. Our study suggested that GB found in the
      herbal Ginkgo biloba may have cancer-preventive activities in BRCA1-mutant
      ovarian epithelial cells.

PMID- 21857522
TI  - Variation in cancer incidence in northeastern Belgium and southeastern
      Netherlands seems unrelated to cadmium emission of zinc smelters.
AB  - Exposure to cadmium has been established to be carcinogenic for humans by the
      International Agency for Research on Cancer, but this is mainly based on studies
      with occupational exposures. The substantial 100 year long emission of cadmium by
      three zinc smelters in the Kempen area across the Dutch-Belgian border might have
      affected the incidence of cancer in this region. Following a study of increased
      risks of lung cancer due to cadmium emission (hazard ratio was 4.2 for high vs.
      low cadmium exposure areas in that study), we used data from the three regional
      population-based cancer registries, covering an area with 2.9 million
      inhabitants. Analyses of observed incidence were carried out for all cancers and
      cancer of the lung, kidney, bladder, prostate, testis, and breast separately. At
      the municipality level standardized incidence ratios were calculated and smoothed
      using a Poisson-gamma or a conditional autoregressive model. To detect clusters
      and to calculate an observed/expected ratio (O/E ratio) for each cluster a
      spatial scan statistic was applied. Significantly increased cancer incidence
      rates were found at a multimunicipality level for female lung cancer (O/E
      ratio=1.2), male and female bladder cancer (O/E ratio male=1.8, O/E ratio
      female=1.7), and prostate cancer (O/E ratio=1.3), none of these clusters being
      located specifically around the area of the zinc smelters. Therefore, the long
      term emission of cadmium by the zinc smelters in the Kempen area did not seem to
      lead to an increase in the incidence of all cancers, and lung, kidney, bladder,
      prostate, testicular, or breast cancer.

PMID- 21857523
TI  - The role of oxidative stress in prostate cancer.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are not only
      byproducts of normal cellular metabolism, but also play important roles in cell
      signaling. However, when the levels of ROS and RNS increase, cells are exposed to
      oxidative stresses, which activate a variety of mechanisms to allow them to cope
      with these changes. Studies have shown that oxidative stress conditions play an
      important role in both the initiation and the progression of prostate cancer by
      regulating molecules such as DNA, enhancers, transcription factors, and cell
      cycle regulators. Other studies have shown that antioxidants, molecules that
      protect cells against oxidative stress, play a role in prevention of prostate
      cancer. This review summarizes the effects of oxidative stress on the development
      of prostate cancer and explores the potential of ROS regulators as preventatives
      for prostate cancer.

PMID- 21857524
TI  - Hypothesis: is the fall in Helicobacter pylori related to the global rise in body
      mass index?

PMID- 21857525
TI  - Diabetes mellitus and increased risk of cholangiocarcinoma:  a meta-analysis.
AB  - Diabetes mellitus (DM) has been reported to be associated with an increased risk
      of several types of cancers. However, its relationship with cholangiocarcinoma
      (CC), which includes intrahepatic cholangiocarcinoma (ICC) and extrahepatic
      cholangiocarcinoma (ECC), remains unclear. We conducted a meta-analysis to assess
      the association between diabetes and the risk of CC (including ICC and ECC). We
      identified studies by a literature search of Medline (from 1 January 1966) and
      Embase (from 1 January 1974), through 30 November 2010, and by searching the
      reference lists of pertinent articles. Summary relative risks (RRs) with
      corresponding 95% confidence intervals (CIs) were calculated with a random
      effects model. A total of 15 articles (10 case-control and five cohort studies)
      were included in this study. The number of reports on DM and risk of specific
      cancer were as follows: CC (n=5), ECC (n=9), and ICC (n=9). Compared with those
      without diabetes, individuals with diabetes had an increased risk of CC (summary
      RRs, 1.60; 95% CI, 1.38-1.87; P=0.992 for heterogeneity), ECC (summary RRs, 1.63;
      95% CIs, 1.29-2.05; P=0.005 for heterogeneity), and ICC (summary RRs, 1.97; 95%
      CIs, 1.57-2.46; P=0.025 for heterogeneity). The funnel plot revealed no evidence
      for publication bias concerning diabetes and the risk of CC (including ICC and
      ECC). These findings strongly support the positive link between DM and the
      increased risk of CC (including ICC and ECC).

PMID- 21857526
TI  - Efficacy and tolerability of intravenous iron dextran and oral iron in
      inflammatory bowel disease:  a case-matched study in clinical practice.
AB  - OBJECTIVES: Iron deficiency anaemia is common in inflammatory bowel disease
      (IBD); however, the optimum route of administration of iron replacement therapy
      is unclear. As inflammation may limit the absorption and efficacy of oral iron,
      we hypothesized that in routine clinical practice IV iron would be more effective
      than oral iron in patients with IBD matched for disease type, extent and
      activity. METHODS: Thirty-three IBD patients who had received IV iron dextran
      (Cosmofer) in 2008-2010 were identified and matched for age, sex, diagnosis and
      baseline disease activity, extent and behaviour to IBD patients given oral iron.
      RESULTS: Patients given IV iron dextran were more anaemic at baseline than those
      receiving oral iron. Although haemoglobin (Hb) concentrations were normalized in
      about a third of patients, and increased significantly in both groups, the mean
      increase in Hb after 8 weeks was greater in the iron dextran group [2.0 g/dl
      (0.3) vs. 0.6 g/dl (0.1), P<0.0001]. Response to oral or IV iron was unrelated to
      age, sex, ethnicity, disease duration, extent or activity. Fifteen percent (five
      out of 33) patients discontinued oral iron because of gastrointestinal side
      effects and a further two out of 35 had anaphylactoid reactions to the IV iron
      dextran test doses. Neither of the iron formulations worsened disease activity.
      CONCLUSION: In routine clinical practice, in anaemic patients with IBD of similar
      type, extent and activity, IV Cosmofer is more efficacious in increasing Hb
      concentration than oral iron. Active disease does not impair the response to
      either IV or oral iron in patients with IBD, and neither product itself worsens
      disease activity.

PMID- 21857527
TI  - Deep brain stimulation increases impulsivity in two patients with obsessive
      compulsive disorder.
AB  - Deep brain stimulation (DBS) is an adjustable, reversible, nondestructive
      neurosurgical intervention using implanted electrodes to deliver electrical
      pulses to areas in the brain. DBS has recently shown promising results as an
      experimental treatment of refractory obsessive-compulsive disorder (OCD). The
      novelty of the treatment requires careful observation of symptoms and possible
      side effects in patients. This case report describes two patients with treatment
      refractory OCD in whom increased voltage of deep brain stimulation targeted at
      the nucleus accumbens increased impulsivity. Voltage increase of stimulation
      resulted in an immediate inflation of self-confidence, irritability and impulsive
      behaviour and was reversed only after lowering the voltage. The mechanisms behind
      DBS are not yet fully understood. Possibly, stimulation in the area of the
      nucleus accumbens affects the corticostriatal circuitry, which plays an important
      role in impulsivity. Location and amplitude of stimulation might be critical in
      inducing these behaviours. These two cases underline the importance of a careful
      clinical assessment of impulsive behaviours during DBS for OCD.

PMID- 21857528
TI  - Triple-rule-out computed tomography angiography with 256-slice computed
      tomography scanners: patient-specific assessment of radiation burden and
      associated cancer risk.
AB  - OBJECTIVES: Risk-benefit analysis of triple-rule-out 256-slice computed
      tomography angiography (TRO-CTA) requires data on associated cancer risks,
      currently not available. The aim of the current study was to provide estimates of
      patient radiation burden and lifetime attributable risk (LAR) of radiation
      induced cancer in patients undergoing typical 256-slice TRO-CTA. MATERIALS AND
      METHODS: Standard step-and-shoot 256-slice TRO-CTA exposures were simulated on 31
      male and 31 female individual-specific voxelized phantoms using a Monte Carlo CT
      dosimetry software. Dose images were generated depicting the dose deposition on
      the exposed body region of the patient. Organ doses were obtained for all
      primarily irradiated radiosensitive organs. Organ doses were correlated to
      patient body size. TRO-CTA effective dose was estimated from (a) organ doses and
      (b) dose-length product data. Recently published sex-, age-, and organ-specific
      cancer risk factors were used to estimate the total LAR of radiation-induced
      cancer. The theoretical risks of radiation-induced cancer to the lung and breast
      following a 256-slice TRO-CTA were compared with the corresponding nominal risks
      for each of the studied patients. RESULTS: The highest organ doses were observed
      for the breast, heart, esophagus, and lung. Mean effective dose estimated using
      organ dose data was found to be 6.5 +/- 1.0 mSv for female and 3.8 +/- 0.7 mSv
      for male individuals subjected to 256-slice TRO-CTA. The associated mean LARs of
      cancer was found to be 41 per 10 female and 17 per 10 male patients. The total
      radiation-induced cancer risk was found to markedly decrease with patient age.
      TRO-CTA exposure was found to increase the intrinsic risks of developing lung or
      breast cancer during the remaining lifetime by less than 0.5% and 0.1%,
      respectively. CONCLUSIONS: The mean theoretical risk of radiation-induced cancer
      for a patient cohort subjected to step-and-shoot 256-slice TRO-CTA may be
      considered to be low compared with the intrinsic risk of developing cancer.

PMID- 21857529
TI  - Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis.
AB  - We meta-analyzed the relationship between depression and HIV medication
      nonadherence to calculate the overall effect size and examine potential
      moderators. Overall, across 95 independent samples, depression was significantly
      (P < 0.0001) associated with nonadherence (r = 0.19; 95% confidence interval =
      0.14 to 0.25). Studies evaluating medication adherence via interview found
      significantly larger effects than those using self-administered questionnaires.
      Studies measuring adherence along a continuum found significantly stronger
      effects than studies comparing dichotomies. Effect size was not significantly
      related to other aspects of adherence or depression measurement, assessment
      interval (ie, cross-sectional vs. longitudinal), sex, IV drug use, sexual
      orientation, or study location. The relationship between depression and HIV
      treatment nonadherence is consistent across samples and over time, is not limited
      to those with clinical depression, and is not inflated by self-report bias. Our
      results suggest that interventions aimed at reducing depressive symptom severity,
      even at subclinical levels, should be a behavioral research priority.

PMID- 21857530
TI  - Swallow evaluation during multichannel intraluminal impedance and pH: an
      alternate method to assess esophageal transit.
AB  - BACKGROUND: Twenty-four-hour multichannel intraluminal impedance and pH (MII-pH)
      esophageal monitoring allows detection of both acid and nonacid gastroesophageal
      reflux episodes. The MII-pH catheter contains 6 impedance segments placed 3, 5,
      7, 9, 15, and 17 cm above the lower esophageal sphincter (LES), plus a pH
      electrode at 5 cm. Multichannel intraluminal impedance and esophageal manometry
      (MII-EM) allows both functional and manometric evaluation of the esophagus. The
      MII-EM catheter contains 4 impedance measuring segments (5, 10, 15, and 20 cm
      above LES) and 5 solid state pressure transducers (within the LES and 5, 10, 15,
      and 20 cm above LES). Five milliliter saline boluses are given in the recumbent
      position when performing an MII-EM study. In our laboratory, all patients have an
      MII-EM study performed before an MII-pH study. In many laboratories, MII-pH is
      done without earlier MII-EM. AIM: To assess accuracy of swallows given before
      ambulatory MII-pH monitoring in detecting esophageal transit abnormalities.
      MATERIALS AND METHODS: Hundred consecutive adult patients, prospectively studied
      (64 female; mean age = 52.6 y), presenting to our laboratory for MII-EM and 24
      hours MII-pH study, also received 10 saline swallows in the recumbent position at
      the beginning of the MII-pH study. Impedance for these swallows was assessed for
      the presence of complete or incomplete transit; defined as presence of bolus
      entry in the 17 cm segment and bolus exit in the 15, 9, and 5 cm segments;
      defined by a rise in impedance above 50% between baseline and the nadir, and
      remaining above this value for at least 5 seconds. Of 10 swallows, the presence
      of 8 or more complete swallows satisfies the MII-EM criterion for diagnosis of
      complete transit. These findings were blindly compared with those of the 10
      saline swallows on the MII-EM study. RESULTS: In 93% of patients, the MII-pH
      swallows gave identical transit diagnosis to the MII-EM. In 2 patients, the
      diagnosis changed from incomplete transit on MII-EM to complete on MII-pH, and in
      5 patients from complete transit on MII-EM to incomplete on MII-pH. With both
      methods, there were 64 patients with complete transit and 29 with incomplete
      transit. Thus, MII-pH swallows had a sensitivity of 94% and a specificity of 93%
      for detection of esophageal transit abnormalities.Comparing the swallow diagnosis
      for each patient, we found that there was a highly significant correlation (P <
      0.0001) for the number swallows with complete (Pearson r = 0.89) and incomplete
      bolus transits (Pearson r = 0.89). There was also a significant correlation (P <
      0.0001) in bolus transit time between both methods (Pearson r = 0.64).
      CONCLUSIONS: Use of 10 saline swallows at the beginning of MII-pH studies is
      accurate, missing bolus transit abnormality in only 2 of 100 patients. It is also
      highly sensitive and specific for detection of esophageal transit abnormalities.
      This method allows detection of patients in whom further evaluation of esophageal
      function may be warranted.

PMID- 21857531
TI  - Infliximab in Crohn's disease-associated toxic megacolon.
AB  - Refractory medical treatment of Crohn disease-associated toxic megacolon usually
      requires surgery, which carries substantial morbidity and mortality. We report a
      case of a woman with steroid and antibiotic-refractory fulminant Crohn colitis
      and ileitis, complicated by a toxic megacolon, who was successfully treated with
      infliximab. Infliximab induced rapid clinical response and remission, thereby
      avoiding emergency (ileo) colectomy. This is the first report of treatment of
      Crohn disease-associated toxic megacolon with infliximab.

PMID- 21857532
TI  - History of tonsillectomy is associated with irritable bowel syndrome.

PMID- 21857533
TI  - Severe chemical colitis due to hydrogen peroxide enema.

PMID- 21857534
TI  - The financial impact of outpatient gastroenterology patient phone calls: an
      activity-based cost analysis.

PMID- 21857535
TI  - Effects of a multifaceted educational program on blood pressure and
      cardiovascular risk in hypertensive patients: the Austrian herz.leben project.
AB  - OBJECTIVE: Although hypertension is the most prevalent risk factor for
      cardiovascular and cerebrovascular morbidity and mortality, the level of blood
      pressure control remains poor. To amplify quality of care in hypertensive
      patients, a multifaceted program consisting of structured educational programs
      for both patients and staff, structured documentation and feedback reports with
      peer comparison, was implemented on a multicentre basis. Main targets were
      improvement of blood pressure control and reduction of cardiovascular risk. A
      provisional reimbursement was provided. METHODS: Patients were eligible for
      inclusion in the program if office blood pressure was uncontrolled (>160/95 or
      >140/90 mmHg) in addition to elevated cardiovascular risk [>15% according to the
      New Zealand Risk Score (NZRS)]. Blood pressure and lipid panels were measured at
      entry in the program and after 12 months. Patients attended four educational
      units held by hypertension nurses and physicians. All data were collected in
      structured documentation sheets and benchmarking reports were provided every 6
      months. RESULTS: Two thousand and forty-one patients were enrolled in the program
      within 5 years and 3 months; 54% female, age 62.8 +/- 11.1years, BMI 29.50 +/-
      7.88 kg/m (mean +/- SD). To date, 744 patients have been seen at 1-year follow
      up. Entry blood pressure was 156.1 +/- 20.8/88.9 +/- 11.1 mmHg. Total cholesterol
      showed mean levels of 207.0 +/- 46.0 mg/dl, low-density lipoprotein 122.3 +/-
      41.6 mg/dl, high-density lipoprotein 57.2 +/- 22.4 mg/dl and calculated
      cardiovascular risk level (NZRS) was 17.28 +/- 8.29%. One year following the
      educational program, blood pressure was reduced to 139.2 +/- 15.6 (P <
      0.001)/82.1 +/- 9.5 mmHg (P < 0.001). NZRS (14.1 +/- 7.2%; P < 0.001) and BMI
      (29.26 +/- 4.92 versus 29.06 +/- 4.99) also improved significantly. CONCLUSION:
      This structured educational program showed its ability to improve intermediate
      outcomes in hypertensive patients. Better blood pressure control and significant
      reduction of the individual cardiovascular risk profile were achieved. A broad
      implementation of the program in the management of hypertension seems justified.

PMID- 21857536
TI  - Low DBP may not be an independent risk for cardiovascular death in revascularized
      coronary artery disease patients.
AB  - OBJECTIVES: It remains controversial whether extremely low DBP is a risk for
      cardiovascular events in patients with coronary artery disease (CAD). Coronary
      revascularization therapy became prevalent in CAD patients. We sought to
      determine the impact of low DBP on cardiovascular events and to investigate the
      predicting factors in revascularized CAD patients. METHODS: We subanalyzed 7180
      stable, chronic CAD patients (median follow-up period 3.6 years) of 9877 patients
      undergoing first coronary artery bypass graft or percutaneous coronary
      intervention in the registry of the Coronary REvascularization Demonstrating
      Outcome study in Kyoto (CREDO-Kyoto). RESULTS: Kaplan-Meier analysis revealed
      that unadjusted cumulative incidence of cardiovascular death was greater in
      patients with preprocedural DBP of less than 70 mmHg than in those with DBP of at
      least 70 mmHg, whereas the cumulative incidences of nonfatal myocardial
      infarction (MI) and of stroke were similar between the two groups. Stepwise
      logistic regression analysis showed that estimated glomerular filtration ratio
      (inversely), pulse pressure, left ventricular ejection fraction of less than
      0.40, history of heart failure, prior cerebrovascular disease, and prior MI were
      independent risks for cardiovascular death in patients with DBP of less than 70
      mmHg. After adjustments for the independent risks, the cumulative hazard ratio
      for cardiovascular death did not differ between patients with DBP of less than 70
      mmHg and those with DBP of at least 70 mmHg. CONCLUSION: Renal insufficiency,
      more advanced vascular damage, and left ventricular systolic dysfunction were
      significant factors accounting for increased cardiovascular death in
      revascularized CAD patients with DBP of less than 70 mmHg. It was suggested that
      after adjustments for these independent risks, low DBP may not be a significant
      risk for cardiovascular death in revascularized CAD patients.

PMID- 21857537
TI  - Pitfalls in the application of distal femur plates for fractures.
AB  - Despite design features intended to aid the surgeon in restoring proper
      alignment, malunion and implant-related problems are relatively common after a
      distal femur fracture treated with plate fixation. This article presents case
      examples of these problems followed by a discussion of the relevant distal
      femoral anatomy, design features of modern locked distal femur plating systems,
      and technical points necessary to avoid malunion and implant-related problems
      when using these devices.

PMID- 21857538
TI  - Does supplemental epidural anesthesia improve outcomes of acetabular fracture
      surgery?
AB  - OBJECTIVE: Addition of epidural anesthesia to general anesthesia is theorized to
      reduce hospital length of stay, improve postoperative pain control, reduce time
      to mobilization, and reduce intraoperative blood loss for operative treatment of
      acetabular fractures. Our hypothesis was that epidural anesthesia would result in
      improvement in short-term outcomes and therefore justify any associated increases
      in anesthesia induction time, treatment costs, or risks. DESIGN: Retrospective
      case-control. SETTING: Academic trauma center. PATIENTS: We identified 163
      patients who underwent open reduction and internal fixation of posterior wall
      acetabular fractures from 2002 through 2007. We excluded patients who were
      intubated before the procedure (n = 20) and patients with incomplete
      intraoperative anesthesia records (n = 5). Patients were divided into two groups:
      Group 1 received combined epidural plus general anesthesia (CEGA) (n = 64) and
      Group 2 received general anesthesia alone (GA) (n = 74). No differences were
      observed between the two groups in terms of age, gender, Injury Severity Score,
      head Abbreviated Injury Score, mechanism of injury, number of associated
      fractures, number of comorbidities, or delay between injury and day of surgery.
      INTERVENTION: General anesthesia with or without epidural anesthesia. MAIN
      OUTCOME MEASUREMENTS: Length of stay, postanesthesia care unit initial and
      discharge pain scores, time to mobilization with physical therapy, estimated
      blood loss, and anesthesia time. RESULTS: : No significant differences were shown
      between the two groups for length of stay (CEGA, 6.2 days; GA, 5.9 days; P =
      0.62; 80% power to detect a difference of 1.3 days), postanesthesia care unit
      initial pain scores (CEGA, 3.5; GA, 3.4; P = 0.92), postanesthesia care unit
      discharge pain scores (CEGA, 2.5; GA, 3.3; P = 0.13), or time to mobilization
      with physical therapy (CEGA, 1.5 days; GA, 1.7 days; P = 0.43). Intraoperative
      blood loss was less in the CEGA group (CEGA, 458 mL; GA, 543 mL; P = 0.05). Mean
      anesthesia time was longer for the CEGA group (CEGA, 85 minutes; GA, 66 minutes;
      P < 0.01). CONCLUSIONS: Although addition of epidural anesthesia added an average
      of 19 minutes to the anesthesia time (P < 0.01), we found no advantage to CEGA
      regarding length of stay, pain scores, or time to rehabilitation. Mean decrease
      of blood loss of less than 100 mL in the CEGA group is unlikely to be of clinical
      significance. Our results contrast findings in support of CEGA in the hip
      arthroplasty literature and question the use of CEGA for posterior wall
      acetabular fractures.

PMID- 21857539
TI  - Evaluation of risk for secondary fracture after removal of a new femoral neck
      plate for intracapsular hip fractures.
AB  - OBJECTIVE: To determine whether a new femoral neck plate has a higher risk for
      secondary fracture after implant removal than the current standard treatment for
      intracapsular hip fractures. METHODS: Six pairs of human cadaver femora (age, 56
      +/- 5.6 years; range, 48-64 years; two female and four male donors) were
      instrumented with the femoral neck plate (FNP) or the compression hip screw
      combined with an antirotation screw (CHS) in a paired study design. After removal
      of the implants, axial compression tests to failure of the bones were conducted.
      Maximum force to failure of the bones after implant removal was determined. Axial
      stiffness of the bones before surgery and after implant removal was determined.
      RESULTS: The FNP resulted in a mean failure load of 4687 +/- 1743 N (mean +/-
      standard deviation) and the CHS resulted in a mean failure load of 4892 +/- 1608
      N with no significant difference between the two implant groups (P = 0.405).
      There was no significant difference in stiffness (P = 0.214) between the FNP
      (1240 +/- 362 N/mm) and the CHS (1293 +/- 304 N/mm). The cavities left by the
      surgery had no effect on the bone stiffness (P > 0.05). The mean failure load of
      all specimens correlated with the bone mineral density in the proximal part of
      the femurs by R2 = 0.715 (P = 0.001). CONCLUSION: The FNP demonstrated a similar
      failure load after implant removal compared with the CHS, although the FNP left a
      39% larger cavity in the bone.

PMID- 21857540
TI  - Observed and expected outcomes in transfer and nontransfer patients with a hip
      fracture.
AB  - OBJECTIVES: Hospitals and providers that accept transfer patients risk lower
      ratings on publically reported quality measures that are inadequately adjusted
      for infirmity and complexity. We compared the outcomes of transferred patients
      and nontransferred patients after treatment of a hip fracture and sought to
      determine if expected outcomes based on an expansion of All Patient Refined
      Diagnosis Related Groups (APR-DRGs) norms are accurately adjusted for transfer
      status. DESIGN: Retrospective cohort study. SETTING: Tertiary care referral
      center. PATIENTS: Four hundred six consecutive patients 65 years and older who
      received operative treatment of an acute hip fracture. INTERVENTION: Patients who
      were transferred from another acute care hospital or a skilled nursing facility
      before treatment were classified as transfer patients (n = 123), and all other
      patients were nontransfer patients (n = 283). MAIN OUTCOME: Groups were compared
      with respect to in-hospital mortality, length of stay (LOS), excess days over the
      geometric mean length of stay (GMLOS), and readmission rate as well as expected
      length of stay (Exp LOS) and expected mortality (Exp Mort) based on APR-DRG norms
      and additional adjustment for transfer status. RESULTS: Transfer patients had
      significantly greater LOS (10.2 vs 9.6 days; P < 0.05), Exp LOS (9.7 vs 7.7 days;
      P < 0.001), Exp Mort (0.07 vs 0.03; P = 0.004), and excess days over the GMLOS
      (4.1 vs 3.3 days; P = 0.025) than nontransfer patients, near-significant greater
      in-hospital mortality (9.8 vs 4.9%; P = 0.069), and similar readmission rates.
      The differences in LOS and Exp LOS were nonsignificant in both transfer (P =
      0.49) and nontransfer patients (P = 0.10). CONCLUSIONS: Patients 65 years and
      older transferred to a tertiary care facility for treatment of an acute hip
      fracture have worse outcome than nontransfer patients. Unadjusted data such as in
      hospital mortality may be misleading, but risk adjustment using the APR-DRG
      methodology and additional correction for transfer status may provide meaningful
      benchmarks.

PMID- 21857541
TI  - Habitual anterior dislocation of the hip in cerebral palsy:  a case report.
AB  - Habitual anterior dislocation of the hip joint is extremely rare. We believe this
      is the first case reported of a habitual anterior dislocation of the hip
      occurring in a child with cerebral palsy. The dislocation was painless, voluntary
      and used to occur every time the child would extend and externally rotate the
      limb. Operative intervention in the form of a varus derotation femoral osteotomy
      and anterior capsulorraphy was planned, but the caregivers of the patient were
      unwilling for the same. Hence, the patient was given an adduction and internal
      rotation brace and was counselled not to perform the activity needed to dislocate
      the hip. This case report calls attention to a unique problem previously not
      reported in cerebral palsy.

PMID- 21857542
TI  - Voluntariness in living-related organ donation.
AB  - Living organ donation requires hurting one person-at least physically-to help
      another. This can be morally justifiable if certain ethical criteria are met,
      among them voluntary and informed consent. In the existing guidance,
      voluntariness is usually vaguely defined as the absence of coercion. This,
      however, is not enough as a basis for making well-considered decisions in
      individual cases. A comprehensive evaluation, procedural safeguards, and critical
      awareness of potential pitfalls can help establish the voluntariness of the
      donor's decision.

PMID- 21857543
TI  - Chemical profile and biological potential of non-polar fractions from Centroceras
      clavulatum (C. Agardh) Montagne (Ceramiales, Rhodophyta).
AB  - The present study reports the Gas Chromatography-Mass Spectrometry (GC-MS)
      evaluation of the hexanes and dichloromethane fractions from extracts of the red
      alga Centroceras clavulatum (C. Agardh) Montagne. Twenty three compounds were
      identified, totaling ca. 42% of both fractions (0.18 g mass extract). The main
      constituents of the fractions were hexadecanoic acid (17.6%) and pentadecanoic
      acid (15.9%). Several secondary metabolites with interesting biological activity,
      such as (-)-loliolide, neophytadiene, phytol were identified. In addition,
      several classes of secondary metabolites, including phenolic compounds (e.g.,
      phenylacetic acid), terpene derivatives, fatty acids, halogenated compound (e.g.,
      2-chlorocyclohexenol), lignoids, steroids, esters, amides (e.g., hexadecanamide),
      ketones, carboxylic acids, aldehydes and alcohols were observed. The occurrence
      of several of these structural classes is described for the first time in this
      species. The same fractions analyzed by GC-MS, and a separate set of polar
      fractions, were evaluated against two life cycle stages (epimastigote and
      trypomastigote forms) of the protozoan Trypanosoma cruzi and against
      phytopatogenic fungi Cladosporium cladosporiodes and C. sphaerospermum. The
      dichloromethane fraction was active against both T. cruzi forms (epimastigote
      IC(50) = 19.1 MUg.mL-1 and trypomastigote IC(50) = 76.2 MUg.mL-1). The hexanes
      and ethyl acetate fractions also displayed activity against both fungi species
      (200 MUg) by TLC-bioautography.

PMID- 21857544
TI  - Pan-Arab consensus statement on the use of botulinum toxin type A in spasticity
      management.

PMID- 21857545
TI  - Is age a prognostic factor of postoperative outcome of lumbar disc herniation
      operations?
AB  - OBJECTIVE: To evaluate the influence of the patients age on preoperative symptoms
      and outcome. METHODS: The general data, symptoms, signs, and neurological
      examination findings were recorded from 511 patients between 2000 and 2006 at
      Vakif Gureba Hospital and Afyon Kocatepe University Neurosurgery Departments,
      Afyonkarahisar, Turkey. The mean follow-up of the patients was 44.7 months. All
      patients younger than 64 were defined as younger patients (n=449). The others
      were defined as elderly patients (n=62). The measuring method of the outcome was
      visual analogue rating scale (VAS). RESULTS: Preoperative and postoperative VAS
      values were found similar in both the younger and older group. Only preoperative
      differences were found in the older group, due to systemic disease. CONCLUSION:
      The outcome was not statistically different in both groups, indicating that age
      is not a valuable prognostic factor for lumbar discectomy.

PMID- 21857546
TI  - Effects of nimodipine on cerebral hemodynamics, and prognosis of diffuse axonal
      injury patients.
AB  - OBJECTIVE: To evaluate the effects of nimodipine on hemodynamic state, vasospasm,
      and short time prognosis of diffuse axonal injury (DAI) patients. METHODS: In a
      prospective, clinical trial double blind study, 40 DAI patients with Glasgow coma
      scale of 5-8 were selected and randomly divided into 2 equal groups. The first
      group was treated with 60 mg of nimodipine every 4 hours immediately after
      admission, and the control group did not receive this treatment. Mean blood flow
      velocity (MFV) and pulsatility index of both middle cerebral arteries were
      measured using transcranial Doppler on the 1st, 3rd, and 10th days of admission.
      Glasgow outcome scale was evaluated one month after admission. This study was
      performed from June 2003 to June 2004 at Imam Medical Center, Tabriz, Iran.
      RESULTS: There were significant differences in MFV among the 3 transcranial
      Doppler, which demonstrated hemodynamic changes in these patients. Nimodipine did
      not have any significant difference on MFV between the treatment and control
      groups. In the nimodipine group, 45% had good prognosis (30% in the control
      group) and nobody had vasospasm on the 10th day Doppler study (15% in the control
      group), although it did not show any statistical significant difference between
      them. CONCLUSION: Nimodipine improved the prognosis and decreased vasospasm,
      however, there was no statistical difference. Therefore, we suggest further
      studies in a larger number of DAI patients.

PMID- 21857547
TI  - Assessment of the atlanto-occipital junction in the MRI of subjects with cervical
      disc herniation.
AB  - OBJECTIVE: To demonstrate the normal limits of Powers ratio and basion dens
      interval in patients with disc herniations. METHODS: The MRI of patients were
      retrospectively evaluated by 2 radiologists. Four hundred and forty-five patients
      who were admitted to Duzce University Hospital with neck pain without history of
      trauma were chosen between January 2004 and July 2006 in this retrospective
      study. The patients were between the ages of 14-80 years. RESULTS: Four groups
      were identified according to the number of disc herniations. The normal limits of
      Powers ratio and basion dens interval were 0.77+/-0.15 and 0.80+/-0.66 in group
      0, 0.76+/-0.14 and 0.81+/-0.76 in group one, 0.75+/-0.13 and 0.80+/-0.71 in group
      2, 0.76+/-0.14 and 0.81+/-0.74 in group 3, and 0.77+/-0.16 and 0.81+/-0.66 in
      group 4. The relationship between the number of disc herniations and Powers ratio
      and basion dens interval was not statistically significant. CONCLUSION: Our
      results were in concordance with the previous studies concerning the Powers ratio
      and basion dens interval. These 2 methods can be used in the MRI of
      atlantooccipital dislocation suspected patients with disc herniations.

PMID- 21857548
TI  - Influence of spinal deformity on pulmonary function, arterial blood gas values,
      and exercise capacity in thoracic kyphoscoliosis.
AB  - OBJECTIVE: To evaluate the influence of thoracic spine curvature on lung
      parameters in kyphoscoliosis. METHODS: Twenty-one patients with kyphoscoliosis
      were evaluated at the Vallabhbhai Patel Chest Institute, Delhi, India from
      January to June 2006 using spirometry, arterial blood gas (ABG), and 6-minute
      walk test. The degree of spinal deformity was measured by Cobb's method for angle
      of scoliosis and angle of kyphosis. RESULTS: There were 13 males and 8 females
      (mean age 47.38+/-20.10 years). Decreased lung volumes, hypoxemia, arterial
      oxygen desaturation, and decreased exercise capacity was observed in patients
      with kyphoscoliosis. The angle of scoliosis ranged from 60-126 degrees (78.1+/
      18.3) and angle of kyphosis ranged from 5-48 degrees (18.05+/-10.5). The forced
      vital capacity (FVC) was 1.92+/-0.8 L (0.66-3.44), and the forced expiratory
      volume in one second (FEV1) was 1.51+/-0.5 L (0.6-2.6). The FEV1/FVC was 60.9+/
      12.9 (42-86%). The partial arterial oxygen tension was 51.7+/-6.9 Hg. The partial
      pressure of carbon dioxide in arterial blood was 49.85+/-7.9 mm Hg. The
      functional oxygen saturation was 84+/-3.7%. No correlation was found between
      pulmonary function test (PFT) or ABG values with the degree of spinal deformity.
      Mean oxygen desaturation (87.48-84.43%) and rise in systolic blood pressure
      (118.48-126.67 mm Hg) during walk test correlated well with degree of spinal
      deformity. CONCLUSION: The severity of pulmonary impairment could not be inferred
      from the angle of scoliosis alone. The 6-minute walk test gives an early
      indication of limitations and correlates well with structural deformity. The PFT
      and ABG parameters do not correlate well with the severity of deformity. Thus,
      the 6-minute walk test must be included in the thorough evaluation of all
      patients with kyphoscoliosis.

PMID- 21857549
TI  - Specific evoked motor response for supraclavicular brachial block.
AB  - OBJECTIVE: To assess and evaluate the accuracy of individual types of evoked
      motor responses (EMRs) for prediction of successful surgical anesthesia following
      peripheral nerve stimulator (PNS) assisted supraclavicular block. METHODS: A
      prospective study was carried out over a period of one and half years from August
      2004 to January 2006, at J. N. Medical College, Aligarh Muslim University,
      Aligarh, India, in 60 patients who underwent various elective operative
      procedures on the upper limb. Any of the EMR, such as forearm flexion or
      extension, carpal flexion, or extension, prono-supination, or finger flexion, at
      a definite current of 0.25 mA for 2 ms was taken as an end point for prediction
      of successful block, and a local anesthetic solution (0.375% Bupivacaine, 30 ml)
      was administered at that level. RESULTS: Complete surgical anesthesia was
      observed in those cases where EMR included: flexion of only second and third
      fingers (n=15/15) or flexion of all 4 fingers with thumb opposition (n=14/14) or
      uncommon flexion of all 4 fingers without movement of any other joint of the
      upper limb (n=2/2), suggesting a sensitivity of 100%. However, thumb opposition
      to the tip of the flexed little finger revealed a success rate of only 83%
      (n=5/6), and other EMRs were followed by high rates of inadequate surgical
      anesthesia or total failure. CONCLUSION: Specific EMR of flexion of second and
      third fingers, or all the 4 fingers are reliable predictors of complete surgical
      anesthesia following PNS assisted single injection supraclavicular nerve block
      with no incidence of pneumothorax and nerve damage.

PMID- 21857550
TI  - The relationship of hypocalcemic convulsions related to nutritional rickets with
      age, gender, season, and serum phosphorus levels.
AB  - OBJECTIVE: To retrospectively evaluate the epidemic characteristics of children
      with hypocalcemic convulsion related to nutritional rickets in the province of
      Kars, Turkey. METHODS: In this study, clinical and laboratory findings of 93
      infants, aged between 1-24 months, who were diagnosed as hypocalcemic convulsive
      resulting from nutritional rickets between January 2000 and June 2005 in Kars
      Maternity and Child Hospital, were investigated. The data of the cases with
      hypocalcemic convulsive rickets were collected from the hospital archive file.
      RESULTS: The mean and median ages of the cases were 8.93 and 6 (1-24) months, and
      66 (71%) were male. Most of the patients were admitted to hospital in February
      and March, whereas 46% were admitted in winter, 44% in spring, 8% in autumn, and
      2% in summertime. Serum calcium levels of all cases were low (mean: 5.4 +/- 0.84
      mg/dl) and serum alkaline phosphate levels were high (mean: 1286 +/- 528 IU/L),
      while serum phosphorus levels were low in 19 (20.4%), high in 8 (8.6%), and
      normal in 66 (71%) patients. CONCLUSION: While evaluating the causes of
      convulsion, hypocalcemic convulsion related to nutritional rickets should be
      considered among the causes as well as age, gender, and season of the year, and
      diagnosis, and treatment should be initiated without delay. In addition, serum
      phosphorus level should also be questioned in the diagnosis of nutritional
      rickets.

PMID- 21857551
TI  - Oral health knowledge in parents of Saudi cerebral palsy children.
AB  - OBJECTIVE: To determine oral health knowledge in parents of cerebral palsy (CP)
      children, and the parents' attitude to oral health of their CP children. METHODS:
      A self-administered questionnaire was utilized to collect the required
      information from the parents. One hundred and six parents, 73 (68.9%) mothers,
      and 33 (31.1%) fathers completed the questionnaire between April and June 2006 in
      Riyadh, Kingdom of Saudi Arabia. RESULTS: All (100%) the parents thought that
      good oral health was important for maintaining optimum general health. Most
      (95.3%) of the parents believed that they can maintain good dental health in
      their CP children by supervising their children's tooth brushing, reducing sugary
      food intake and making regular visits to a dentist. A significantly high
      (p=0.005) percentage of high education parents (96.8%) had heard of fluoride as
      compared with low education parents (79.5%). CONCLUSION: The overall oral health
      knowledge and attitude of parents of CP children is satisfactory.

PMID- 21857552
TI  - Psychological health of mothers caring for mentally disabled children in Qatar.
AB  - OBJECTIVE: To compare the prevalence of psychiatric morbidity among mothers of
      mentally disabled children and mothers of non-disabled children, and to identify
      the determinants associated with psychiatric morbidity. METHODS: A comparative
      cross-sectional study was conducted in Qatar from January to June 2005 to compare
      the prevalence psychiatric morbidity by using the General Health Questionnaire
      (GHQ-12) among 195 mothers of mentally disabled children selected as a study
      group, and 139 mothers with non-disabled children as a comparison group. RESULTS:
      The prevalence of psychiatric morbidity was higher among mothers caring for
      mentally disabled children than mothers of non-disabled children in the
      comparison group. The study found the following predictors for developing
      psychiatric morbidity: having more than one disabled child, mentally disabled
      child less than 5 years of age, disabled child is first in order of birth,
      presence of chronic illness in addition to the mental disability, and presence of
      other type of disability besides the mental one. We also found that educating
      mothers in caring for a disabled child has a protective effect on developing
      psychiatric morbidity. CONCLUSION: Mothers of mentally disabled children have
      poorer psychological health than mothers of non-disabled children. Shifting the
      rehabilitation services from child-centered to family-centered services through
      providing supportive services is recommended.

PMID- 21857553
TI  - Dissociative disorders and dissociative symptoms among veterans of the Iraq-Iran
      war suffering from chronic post-traumatic disorder.
AB  - OBJECTIVE: To evaluate any dissociative disorders in patients with post traumatic
      stress disorder (PTSD), and find any relationship between dissociation and
      related variables in these patients. METHODS: A case controlled study carried out
      among 130 male patients with PTSD, and 130 matched individuals from the normal
      population. The study was carried out between January and September 2005, at
      Beheshti Psychiatric Hospital, Kerman, Iran, Demographic data and history of
      childhood physical abuse and self-harm in both groups were recorded. The severity
      of PTSD was measured by Davidson PTSD scale in the study group. Dissociative
      symptoms were evaluated with the dissociative experience scale (DES). For
      evaluating dissociative disorders, the dissociative disorder interview schedule
      (DDIS) was used. Data were analyzed by SPSS software. RESULTS: The mean age (+/-
      SD) of veterans was 41.46 (+/-5.09) years, and the mean age of going to the
      combat area was 29.4 (+/-5.015). The mean duration of involvement in combat was
      27.8 (+/-23.44) months. The mean DES score in the study group was 26.01 (+/
      12.31) and was 9.58 (+/-7.23) in the control group (F=1.171, p<0.0001). The mean
      score (+/-SD) of Davidson PTSD scale was 54+/-96 in the study group. The most
      prevalent dissociative disorder in the study group was psychogenic amnesia.
      CONCLUSION: Many veterans with the impression of chronic PTSD may have an
      additional diagnosis of dissociative disorders.

PMID- 21857554
TI  - The effect of nicotine on the recovery of rats receiving anesthesia.
AB  - OBJECTIVE: To determine the effect of intraperitoneal (ip) nicotine on the
      recovery of rats receiving general anesthesia compared with placebo. METHODS: The
      placebo controlled experimental study was conducted in the Faculty of Medicine,
      Gazi University, Turkey, between April and May 2005. Twenty-one male and 21
      female rats were randomly divided into 3 groups. Group C (n=14), comprising a
      female group CF (n=7), and male group CM (n=7) received ip 0.9% sodium chloride
      (NaCl), group P (n=14), comprising a female group PF (n=7), and male group PM
      (n=7) received ip propofol 150 mg/kg, and group NP (n=14), comprising a female
      group NPF (n=7), and male group NPM (n=7) received 0.4 mg/kg ip nicotine followed
      by 150 mg/kg propofol after 15 minutes. For the evaluation of recovery period,
      tail pinch test was used, and for cognitive performance, the radial arm maze test
      was used. RESULTS: The number of entrances and exits decreased in group P
      significantly compared to group C (p<0.05), and the decrease in group PF was
      higher than it was in group PM. Entrance and exit in group NP increased
      significantly compared to group P (p<0.05). The increase in entrance and exit in
      group NPF was much higher compared to group NPM. The recovery period in group NP
      was significantly shorter than in group P (p<0.05). CONCLUSION: The ip
      administration of nicotine in rats shortens the recovery from propofol anesthesia
      and improves cognitive performance.

PMID- 21857555
TI  - Episodic nausea and abdominal sensations as sole manifestations of simple partial
      seizures.
AB  - In adults, seizures manifesting with abdominal complaints are usually associated
      with complex partial or secondary generalized seizures. Also, seizure periodicity
      is not expected in postmenopausal women. We encountered a 72-year-old woman with
      episodic nausea and abdominal pain that usually occurred with predictable
      regularity. When symptoms persisted after extensive gastrointestinal
      investigations and cholecystectomy, she was referred to us and the diagnosis of
      simple partial seizures was suspected. Both EEG and brain MRI were normal. The
      diagnosis was established by video/EEG monitoring, which recorded several typical
      clinical events associated with right temporal ictal discharges. Because
      treatment with several antiepileptic medications caused intolerable side effects,
      the patient is now maintained on a low dose of Lamotrigine, which reduced seizure
      frequency and severity. This patient demonstrates that 'abdominal' complaints,
      although rare, may be the sole manifestation of simple partial seizures. Unless
      considered in the differential diagnosis, the patient may undergo unnecessary and
      potentially harmful procedures.

PMID- 21857556
TI  - Spinal intramedullary cavernous hemangioma.
AB  - The spinal cord can be involved in a variety of disease processes. These can be
      congenital or acquired. An acute onset of symptoms usually allows a defined set
      of causes to be considered including trauma, ruptured vascular anomalies,
      demyelination, and myelitis. Intramedullary cavernous hemangioma of the spinal
      cord is a congenital or acquired vascular malformation, and one of the rare
      causes of hematomyelia. We present such a case, and discuss the symptoms,
      diagnosis, and suggested best treatment options based on a review of present day
      literature.

PMID- 21857557
TI  - An unusual association of optic hydrops and Reiter's syndrome.
AB  - The association of optic hydrops and Reiter's syndrome in the literature has not
      been mentioned previously. This syndrome characteristically consists of 3
      manifestations: arthritis, urethritis, and conjunctivitis. A 42-year-old woman
      with a history of Reiter's syndrome presented with progressive vision disturbance
      in her left eye and with headache. Orbital MRI demonstrated enlarged perioptic
      nerve subarachnoidal space on the left side.

PMID- 21857558
TI  - A case of large scalenus minimus muscle.
AB  - During the dissection of an 80-year-old, white, male cadaver, a large scalenus
      minimus muscle was detected on the right side. Scalenus minimus muscle, a fiber
      bundle which strengthens the suprapleural membrane, arises from the anterior
      tubercle of the transverse process of the 7th cervical vertebra, and inserts to
      the inner border of the first rib and cupula pleura. In the present case, the
      scalenus minimus muscle on the suprapleural membrane was large on the right side.
      Its origin was on the anterior tubercle of the transverse process of the 7th
      cervical vertebra, and the muscle was located between the C7 and C8 anterior
      rami. The present case is noteworthy because of its great dimension and relation
      with the brachial plexus. Apart from its importance in cervical region anesthesia
      and surgery, such an anatomical structure can lead to several clinical conditions
      both by spasm and compression such as neurogenic thoracic outlet syndrome.

PMID- 21857559
TI  - Variant structures potent to compress the median nerve in the arm.
AB  - The most commonly known nerve compression syndrome is carpal tunnel syndrome, in
      which the median nerve is compressed at the wrist. Along with the pathological
      processes, some of the anatomically variant structures can also compress the
      nerves and often leads to confusion in the diagnosis and treatment if one is
      unaware of such possible anatomical variants. Here, we present a case of possible
      median nerve compression by an additional belly of coracobrachialis and a fascial
      sheet from the brachialis, and we also discuss the other possible structures that
      can compress the median nerve.

PMID- 21857561
TI  - Polyneuropathy associated with Wilson's disease.

PMID- 21857560
TI  - Absence of musculocutaneous nerve associated with a third head of biceps brachii
      muscle and entrapment of ulnar nerve.
AB  - Variations in the formation of the brachial plexus and in the course of its
      branches are not as uncommon as was once thought. A description of the
      abnormalities and complexities of the anatomy of the upper arm is very important
      with regard to surgical approaches. This case study reports a combined absence of
      musculocutaneous nerve associated with a third head of biceps brachii muscle in
      the left upper arm of an adult male cadaver. Moreover, the left ulnar nerve is
      entrapped within the substance of the medial head of the triceps muscle. The
      clinical implications, as well as the possible clinical symptoms resulting from
      these anomalies are discussed.

PMID- 21857562
TI  - An unusual presentation of late onset multiple sclerosis with amyotrophic lateral
      sclerosis.

PMID- 21857563
TI  - Late daytime naps may cause drowsiness after coronary bypass graft operation in
      the first postoperative week.

PMID- 21857564
TI  - Plasma adrenomedullin in acute ischemic stroke.

PMID- 21857565
TI  - A girl with recurrent tonic spasm.

PMID- 21857566
TI  - Pyogenic ventriculitis secondary to ruptured brain abscess.

PMID- 21857567
TI  - The value of seizure semiology in lateralizing and localizing partially
      originating seizures.
AB  - Diagnosing epilepsy depends heavily on a detailed, and accurate description of
      the abnormal transient neurological manifestations. Observing the seizures yields
      important semiologic features that characterize epilepsy. Video-EEG monitoring
      allows the identification of important lateralizing (left versus right), and
      localizing (involved brain region) semiologic features. This information is vital
      for identifying the seizure origin for possible surgical interventions. The aim
      of this review is to present a summary of important semiologic characteristics of
      various seizures that are important for accurate seizure lateralization and
      localization. This would most likely help during reviewing video-EEG recorded
      seizures of intractable patients for possible epilepsy surgery. Semiologic
      features of partial and secondarily generalized seizures can be grouped into one
      of 4 categories including; automatism, speech, motor, and autonomic features.
      These features will be discussed in detail in this review. However, seizure
      semiology should be correlated with EEG and MRI findings. Accurate identification
      of the seizure origin is more likely if focal EEG onset and MRI findings were
      concordant with the clinical semiology.

PMID- 21857568
TI  - Protective role of vitamin E on the harmful effects of toluene on brain tissue.
AB  - OBJECTIVE: To determine the protective effects of vitamin E against the damage
      inflicted by reactive oxygen species during toluene induced brain injury in rats
      using histopathological, biochemical, and behavioral parameters. METHODS: Twenty
      eight Wistar albino male rats were studied at Hacettepe University Faculty of
      Medicine Laboratories and Gazi University Faculty of Medicine Metabolism
      Laboratory in 2006. The rats were divided into 4 groups as follows: control
      group, toluene only treated group, both toluene and vitamin E treated group, and
      vitamin E only treated group. Histopathological changes were observed by
      hematoxylin and eosin staining and the TUNEL method. Serum lipid peroxide levels
      were measured by the thiobutyric acid method, and the open field test was used
      for behavioral testing. RESULTS: Our results show that edema between cells in the
      neuropil, particularly beneath the pia mater, and around congested blood vessels
      was observed in all groups with different severity. However the pyknotic neurons,
      in addition to infiltrative cells, were observed in the toluene group to be
      decreased by the administration of vitamin E, which can be confirmed by the
      euchromatic nucleated neurons in the cortex of both the toluene and vitamin E
      treated groups. The levels of malondialdehyde in each group also confirmed these
      histopathological findings. Significant differences were also found in the open
      field test between the groups. CONCLUSION: The differences between the toluene
      and vitamin E groups in biochemical, histologic, and behavioral examinations,
      supports the antioxidant protective role of vitamin E against the harmful effect
      of toluene on the brain.

PMID- 21857569
TI  - Protective effect of omega-3 fatty acids in a rat focal cerebral ischemia
      reperfusion model.
AB  - OBJECTIVE: To investigate possible neuroprotective effects of dietary
      supplementation of fish oil in brain ischemia-reperfusion (I/R). METHODS: This
      investigation took place in the Experimental Research Unit, Firat University,
      Elazig, Turkey, from January-February 2006. The study was carried out on 12 male
      Wistar rats; divided into 2 groups: I/R (control) and I/R + omega-3 essential
      fatty acids (EFA) (experiment). The rats in the I/R group received only ordinary
      rat food before middle cerebral artery (MCA) occlusion. The I/R + omega-3 EFA
      group received omega-3 fatty acid daily via intragastric gavage (300 mg/kg
      Marincap capsule) with normal food before MCA occlusion for 30 days. Structural
      alterations in the brain tissues were semi-quantitatively analyzed (0: absent, +:
      slight, ++: moderate, +++: severe). RESULTS: There was evident severe (+++)
      edema, vacuolization, and eosinophilic degeneration in the I/R group, while only
      slight (+) edema and eosinophilic degeneration in the I/R + omega-3 EFA group in
      which no vacuolization was determined. These findings are consistent with the
      available studies in this field. CONCLUSION: Results from this study indicate the
      beneficial effects of omega-3 EFA supplementation in prevention of I/R - induced
      damage in rats.

PMID- 21857570
TI  - C-reactive protein, fibrinogen, lipoprotein (a), and lipid profile levels and
      platelet counts in ischemic stroke patients.
AB  - OBJECTIVE: To ascertain the most prevalent risk factor for stroke. METHODS: We
      performed a descriptive and analytical prospective study on patients with stroke
      admitted to the neurology wards of Imam Hospital, Tabriz, Iran during 2004 and
      2005. The study comprised 100 ischemic stroke (IS) patients consisting of 46 men
      and 54 women with a mean age of 67 +/- 15, and 100 age and gender matched
      apparently healthy subjects. Plasma levels of C-Reactive protein (CRP),
      fibrinogen, platelet counts, lipoprotein (a) (LP (a)), high-density lipoprotein
      cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total
      cholesterol (TC), and triglycerides (TG) were measured in both patients and
      controls. Background disease was also investigated in the patients. Hemorrhagic
      and embolic stroke patients were excluded from the study. RESULTS: We found no
      significant difference in serum fibrinogen, HDL-c levels, and platelet counts
      between patients and control subjects, however, levels of LP (a), TG, LDH-c, and
      CRP were significantly higher in patients than controls. Among the predisposing
      background illnesses, the most common risk factors were hypertension and
      hyperlipidemia. The frequency of studied risk factors among patients was: no risk
      factors (20%), one risk factor (32%), 2 risk factors (36%), and 3 risk factors
      (12%). CONCLUSION: Hypertension was the most prevalent background disease in IS
      patients. We also found that although there is close relationship in the
      incidence of IS with levels of LP (a), TC, TG, LDL-c, and CRP, the cutoff point
      frequency of fibrinogen, CRP, LP (a), and platelet counts was variable from
      patient to patient.

PMID- 21857571
TI  - Pregnancy-related strokes in southeast Turkey.
AB  - OBJECTIVE: To evaluate the presentation, timing, etiology, risk factors,
      mortality, and outcome of ischemic stroke (IS), intracerebral hemorrhagic stroke
      (ICH/HS), and cerebral venous thrombosis (CVT) occurring during pregnancy and the
      postpartum period in southeast Turkey. METHODS: The study was carried out from
      September 2003 to September 2005 at the emergency department of Dicle University
      Hospital in the southeast part of Turkey. Thirty-eight stroke patients, 18-42
      years of age with a diagnosis of stroke during pregnancy or within 6 weeks of
      delivery were included. The records were retrospectively reviewed for
      presentation, gestational ages, strokes subtypes and time, stroke sort, stroke
      place, etiology, risk factors, hospital stay, mortality, and outcome. RESULTS:
      Thirty-eight patients were identified, including 18 with IS, 15 with ICH, and 5
      patients with CVT. Most events (89.5%) occurred in the third trimester and the
      postpartum period. A definable cause was identified in 61.1% of IS and 60% of
      CHS. Causes of IS include pre-eclampsia or eclampsia (22.2%), hypercoagulable
      states (16.7%), and a diverse array of other causes, including cardio embolism
      (5.5%) and hypotension (16.7%). Pre-eclampsia/eclampsia (46.7%) and ruptured
      atriovenous malformation (6.7%) were the primary causes of ICH. The mortality
      rate for all patients was 34.2%. CONCLUSION: The etiology of stroke in pregnancy
      and the postpartum period is diverse. Strokes are most likely to occur in the
      third trimester and postpartum period and cluster in the first postpartum week.
      Mortality is high in patients with ICH. Pre-eclampsia and eclampsia are common
      causes of strokes.

PMID- 21857572
TI  - A clinical and electrodiagnostic study of diabetic neuropathy at Jordan
      University Hospital.
AB  - OBJECTIVE: To study diabetic neuropathy (DN) at Jordan University Hospital (JUH)
      with the aim of assessing age/gender distribution, risk factors, and other
      diabetic microvascular complications, clinical manifestations, results of nerve
      conduction studies (NCS), and treatment modalities, and to compare these findings
      with those from Western and other Middle/Far Eastern literatures. METHODS: Among
      562 patients with diabetes mellitus (DM) seen over a 2-year-period from January
      2003 to January 2005, at the Diabetes center at Jordan University Hospital (JUH),
      110 patients (10 DM type 1; 100 DM type 2) were studied retrospectively. RESULTS:
      The prevalence of DN was 20%. The mean age was 55.4 years (range 23-75), with 62
      females and 48 males. The most common risk factors for DN were old age, long
      duration of DM, mean hemoglobin A1c, and hypertension. Almost 50% of patients had
      additional retinopathy, renal involvement, or both. The most common clinical
      symptoms were distal numbness/paresthesiae in the limbs (60% of patients) and the
      neurological examination was normal in 2/3 of patients (only 20% had stocking
      hypoesthesia to pain and temperature and absent ankle jerks). The NCS showed an
      axonal neuropathy mainly affecting the lower limbs, especially sensory fibers
      (abnormal sural sensory action potential in 98% of patients). Anticonvulsants
      (carbamazepine and gabapentin) were used efficiently in 50% of patients as
      symptomatic treatment, while tricyclic antidepressants were used as add-on in
      only 23 patients, due to anticholinergic side effects. CONCLUSION: In comparison
      with other studies, ours shows a lower prevalence of DN, similar age distribution
      with however, a predominance of females, similar risk factor profiles,
      clinical/NCS findings, and treatment modalities.

PMID- 21857573
TI  - Sagittal alignment of the lumbar spine in a Turkish population.
AB  - OBJECTIVE: To understand the normal lumbar spine in the sagittal plane, and the
      range of lumbar lordosis. METHODS: This study was carried out in the Department
      of Anatomy, School of Medicine, Duzce University, Duzce, Turkey in the year 2005.
      We retrospectively reviewed T1-weighed sagittal spin-echo MRIs of the lumbar
      spine in 413 individuals (188 male, 225 female) aged between 13-82 years, and
      evaluated the angle of lumbar lordosis (ALL), sacrohorizontal angle (SHA), and
      lumbosacral angle (LSA). RESULTS: The ALL and SHA were significantly greater in
      females than in males (p<0.05). Weak, but significant correlations were detected
      between age and ALL, SHA, and LSA for females (p<0.05). The LSA was significantly
      greater for individuals over 41 years (p<0.05) when the entire study group was
      considered, and it was also significantly greater for individuals over 51 years
      in females (p<0.05). The LSA was significantly greater in the 7th decade than in
      the 3rd decade (p<0.05). CONCLUSION: The results of this study provide insight
      into the sagittal alignment of the lumbar region for a Turkish population, and
      can serve as a reference for further clinical studies to improve the planning of
      spinal surgery.

PMID- 21857574
TI  - Evaluation of quality of sleep and effecting factors in hospitalized
      neurosurgical patients.
AB  - OBJECTIVE: To evaluate the quality of sleep and effecting factors in hospitalized
      patients in a neurosurgery clinic. METHODS: This research was conducted as a
      descriptive study in a neurosurgery clinic of a University Hospital, in Turkey,
      between November 2005 and June 2006. The study sample consisted of 102 patients
      who met the inclusion criteria and agreed to participate in the study. Data were
      collected using the "Questionnaire Form," which included socio-demographic,
      illness, sleep, and hospital characteristics, and the "Pittsburgh Sleep Quality
      Index" (PSQI). The data obtained were assessed by SPSS 10.00 Program, using
      number, percentage, arithmetic mean, t-test, variance, and correlation analysis.
      RESULTS: The mean age of the patients was 43.22+/-16.72 years, 54.9% were
      females, and 72.5% were married. Hospitalization duration of the patients was
      14.31+/-8.97 days on average, 84.3% had previous hospital experience, and 72.5%
      had knowledge about their illnesses. Of them, 51% expressed a sleep problem. Pain
      (41.2%) and noise (31.4%) was found to affect the sleep quality of hospitalized
      patients. Of the patients hospitalized in the neurosurgery ward, 64.7% were found
      to have poor quality of sleep prior to admission, while poor quality of sleep was
      determined for 49% before being discharged from the hospital. However, a better
      sleep quality was noted prior to discharge, compared to that at their admission
      to the hospital. CONCLUSION: Varied degrees of quality of sleep have been
      reported by the patients and influences of personal and environmental factors on
      sleep quality have been noted. Strategies to enhance physical and mental comfort,
      and to minimize disruptions should positively enhance sleep quality.

PMID- 21857575
TI  - Bone loss and bone turnover in acute and chronic spinal cord injured patients.
AB  - OBJECTIVE: To investigate bone loss and the rate of bone turnover in individuals
      with spinal cord injury (SCI), and to compare the results with those healthy
      controls. METHODS: This cross-sectional, controlled study was performed between
      January and December 2005, in the Istanbul Physical Medicine and Rehabilitation
      Training Hospital, Istanbul, Turkey. Forty-eight patients with SCI were included
      in the study. The control group consisted of 47 age and sex matched healthy
      subjects. Bone density was measured at the proximal hip region by dual-energy X
      ray absorptiometry. Serum levels of osteocalcin (OC) and C telopeptide of type 1
      collagen (CTX) were measured. RESULTS: Femur neck and femur total bone mineral
      density values in the SCI patients and control group were 0.894 (0.188), 0.911
      (0.185), and 0.994 (0.116), 1.063 (0.132) (p<0.03, p<0.000). Serum levels of OC
      and CTX were significantly increased in patients (p<0.015, p<0.000). Femur bone
      density in both neck and total regions showed a significant decrease in the SCI
      patients with longer injury duration (p<0.001, p<0.000). Serum CTX levels were
      markedly elevated in the first year of SCI. However, serum OC level showed no
      difference for the injury duration. CONCLUSION: Significant bone loss was found
      at the proximal hip in SCI patients. Serum biochemical markers were also
      significantly higher in the patient group than the healthy controls. The bone
      density was lower in the long-standing SCI patients, although serum CTX levels
      were higher in the first 12 months after injury.

PMID- 21857576
TI  - Treatment with Centalla asiatica (Linn) fresh leaf extract enhances learning
      ability and memory retention power in rats.
AB  - OBJECTIVE: To investigate the role of Centella asiatica (CeA) fresh leaf extract
      treatment on the behavior, especially learning and memory, of adult rats.
      METHODS: Adult rats (2.5 months old) were fed with 2, 4, and 6 ml/kg body of
      fresh leaf extract of CeA for 2, 4, and 6 weeks. After the treatment period the
      rats were subjected to spatial learning (T-Maze) and passive avoidance tests
      along with age matched normal and saline control rats. The data were compared
      with those of age matched control rats. The study was conducted at the Melaka
      Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka,
      India between December 2001 and February 2005. RESULTS: The rats treated with a
      higher dose (6 ml) of CeA showed improvement in spatial learning performance,
      namely, increased (p<0.001) number of alternations and decreased (p<0.001)
      percentage bias during spontaneous alternation test and increased (p<0.001)
      percentage bias during rewarded alternation test. They also showed enhanced
      memory retention power, namely, less (p<0.001) time spent in the small
      compartment during the retention period of passive avoidance test. CONCLUSION:
      This indicates that treatment with higher doses of CeA fresh leaf extract
      enhances learning ability and memory retention power in adult rats.

PMID- 21857577
TI  - Association between hirsutism and mental health.
AB  - OBJECTIVE: To ascertain the prevalence of psychiatric disturbances in a sample of
      hirsute women. METHODS: This case-control study was carried out on 100 hirsute
      women referred to a dermatology clinic in Sari, Mazandaran, Iran from 2004 to
      2005. One hundred non-hirsute healthy control subjects were case-matched for
      demographic variables and completed the symptom checklist revised (SCL-90-R)
      instrument. Data were analyzed using SPSS software (version 11). RESULTS: Forty
      three percent of the women reported psychological distress, with the most common
      subscales being interpersonal sensitivity, paranoid, depression, and obsessive
      compulsive. In the control group, 42% were suspicious for mental disorders. There
      was no significant difference between the 2 groups. CONCLUSION: No significant
      difference concerning mental health was reported between the hirsute and non
      hirsute women. This maybe due to patients having adapted to their disorder due to
      the presence of high social stress conditions in Iran.

PMID- 21857578
TI  - Thoracic aortic aneurysm presenting only as vocal cord paralysis.
AB  - We present a case of unilateral vocal cord paralysis in a 76-year-old Saudi male
      presenting with hoarseness of voice caused by thoracic aortic aneurysm. Here, we
      are illustrating a rare entity of thoracic aortic aneurysm presenting only with
      hoarseness of voice to draw attention to unusual clinical manifestations of this
      serious underlying aortic pathology.

PMID- 21857579
TI  - Intracranial hydatid cyst. Dilemma in diagnosis and management.
AB  - Intracranial hydatid disease is a parasitic infection that affects children in
      endemic areas such as the Mediterranean, South America, and Australia. In non
      endemic areas, it is rare and may pose a diagnostic dilemma. We review a boy who
      presented with a right cerebral cyst. All investigations were negative, and
      hydatid cyst was encountered upon intra-operative exploration. We review the
      available diagnostic modalities, and the difficulty in reaching a preoperative
      diagnosis. We also review the surgical and medical treatment strategies. A
      cerebral hydatid cyst should be considered in children with cystic brain lesions
      even in non-endemic areas. Since serologic tests are frequently negative, the
      most reliable methods in reaching a diagnosis are radiological evaluation and
      histopathological examination. The cyst has a typical appearance on CT and MRI
      and this bears special importance on the treatment strategy where the cyst is
      best removed intact to avoid recurrence or anaphylaxis.

PMID- 21857580
TI  - Transient opsoclonus-myoclonus syndrome secondary to neuroblastoma.
AB  - We report a 2.5-year-old girl who presented with acute history of fluctuating
      level of consciousness in the form of drowsiness, extreme irritability, and
      involuntary abnormal movements in the form of shaking of the whole body. She was
      treated with acyclovir empirically, contemplating herpes simplex virus
      encephalitis. Overtime she improved substantially. The opsoclonus, myoclonus, and
      ataxia disappeared without treatment. However, 6 weeks later she presented again
      with classic opsoclonus-myoclonus syndrome. The investigations revealed
      neuroblastoma. This case illustrates that transient opsoclonus-myoclonus may
      occur with neuroblastoma and should not be assumed to be due to viral cause.
      Thus, a thorough search for occult neuroblastoma should be initiated even if
      opsoclonus-myoclonus resolves spontaneously.

PMID- 21857581
TI  - Meningitis revealing pancreatic carcinoma.
AB  - Meningeal carcinomatosis is an uncommon metastatic complication of systemic solid
      tumors. The diagnosis is based on the presence of malignant cells in the
      cerebrospinal fluid. The sensibility of cerebrospinal fluid testing in detecting
      the neoplastic cells improves when repeating lumbar punctures. Magnetic resonance
      imaging could help in establishing the diagnosis. The prognosis of carcinomatous
      meningitis is poor, especially when the primitive neoplasm is initially unknown.
      We report the case of a patient presenting with sudden bilateral visual decrease,
      headaches, and vomiting. Signs of meningeal irritation were found. Cerebrospinal
      fluid analysis showed malignant cells consistent with an adenocarcinoma.
      Abdominal echography and MRI concluded in a nodule of the cephalic portion of the
      pancreas. Carcinomatous meningitis rarely complicates pancreatic cancers.

PMID- 21857582
TI  - Isolated lesion of the cervical spine in a case of neuro-Behcet.
AB  - Behcet's disease is characterized by small vessel vasculitis and involvement of
      multiple systems. In neuro-Behcet cases, spinal cord involvement is approximately
      10-18%. Spinal cord lesions are often associated with cerebral or brainstem
      lesions, and isolated spinal cord involvement in Behcet's disease is very rare.
      Here, we report a case with an isolated lesion of the cervical spine.

PMID- 21857584
TI  - Cannabis use and psychiatric disorders.

PMID- 21857583
TI  - Spinal cord compression due to intraspinal extramedullary hematopoiesis in
      thalassemia intermedia.
AB  - Extramedullary hematopoiesis is a common phenomenon in thalassemia. During the
      disease there are very rare occasions when compensatory hematopoietic tissue is
      located in the intraspinal epidural space, causing spinal cord compression. This
      complication requires urgent neurosurgical consideration and decision for further
      treatment. We present a case of thoracic spinal cord compression secondary to
      extramedullary hematopoiesis in thalassemia intermedia, treated with irradiation
      therapy. The therapeutic options are discussed, and the need for more explicit
      therapeutic directions is highlighted.

PMID- 21857585
TI  - Hyperemesis gravidarum complicated by Wernicke's encephalopathy.

PMID- 21857586
TI  - A 40-year-old man with coma.

PMID- 21857587
TI  - Pediatric epilepsy and psychopathology.
AB  - The association of psychiatric disorders and pediatric epilepsy is under
      appreciated by clinicians. Behavioral disorders, especially depression, are often
      perceived as "reactionary" processes. In fact, these comorbid disorders can be
      more disabling than the epilepsy itself. This review discusses the common
      behavioral comorbidities associated with epilepsy including autistic spectrum
      disorders, psychosis, attention deficit hyperactivity disorders, and mood
      disorders.

PMID- 21857588
TI  - Detection of rifampin resistant tuberculosis meningitis by polymerase chain
      reaction linked single strand conformation polymorphism analysis of cerebrospinal
      fluid.
AB  - OBJECTIVE: To rapidly detect rifampin resistance in Mycobacterium tuberculosis
      isolates causing meningitis in northeast Iran. METHODS: This study presents the
      results of a polymerase chain reaction-single strand conformation polymorphism
      (PCR-SSCP) analysis for the evaluation of rifampin resistance directly from the
      CSF of 47 patients strongly suspicious to have tuberculosis meningitis in Emam
      Reza University Hospital, Mashhad, Iran over 3 years (2002 to 2005). Each CSF
      sample underwent microscopic examination, culture and DNA amplification by 2 PCR
      protocols and subsequent detection of mutations by SSCP analysis. RESULTS: Among
      these patients, no mutations were revealed in the rpoB segment by SSCP.
      CONCLUSION: The SSCP analyses of these samples shows complete susceptibility to
      rifampin. The use of this method can radically reduce the time needed to provide
      clinicians with data useful in aiding the selection of appropriate drugs.

PMID- 21857589
TI  - Efficacy of Adcon-L gel or Healon-GV in epidural fibrosis after lumbar
      microdiscectomy.
AB  - OBJECTIVE: To evaluate the efficacy of anti-adhesion barrier agents following
      lumbar microdiscectomy. METHODS: Healon GV or Adcon-L was applied to a
      laminectomy defect overlying the duramater in 60 patients assigned to 3
      randomized groups: Group I - Adcon-L (n=21), Group II - Healon GV (n=21), and
      Group III - control group, no adhesion barrier used (n=18). We conducted this
      study between 2004 and 2006 at Selcuk University, Konya, Turkey. RESULTS: No
      significant difference was found between the 3 groups either in the outcome
      measurements according to visual analogue score and the Oswestry Disability Index
      or in the radiological evaluation of epidural fibrosis by application of those
      anti-adhesion barrier agents. When comparing group III with groups I and II, we
      could not find a statistically significant difference in the clinical results and
      in the outcome measures (p>0.01). CONCLUSION: The epidural application of popular
      anti-adhesion barriers, after lumbar microdiscectomy was not found to be
      effective regarding outcome measures in human spinal surgery.

PMID- 21857590
TI  - Effect of iloprost on adrenal medullary grafts in central nervous system
      transplantation and apoptosis.
AB  - OBJECTIVE: To investigate whether iloprost, a stable analog of prostacyclin, is
      useful for the preservation of neural grafts in transplantation surgery. METHODS:
      This study was conducted at the Microsurgery Laboratory of the Department of
      Neurosurgery, Faculty of Medicine, Ankara University, Ankara, Turkey in 2003. The
      animals (rabbits) were divided into 3 groups. In group I, autografts taken from
      the adrenal medulla were stored in 0.9% sodium chloride (NaCl) solution for 45
      minutes before transplantation. In group II, autografts taken from the adrenal
      medulla were stored in iloprost solution (50 ng/ml) for 45 minutes before
      transplantation. Graft transplantation was not performed in the third group.
      RESULTS: In group I, the grafts partially preserved their viability. In group II,
      the large adrenal medullary cells had evident euchromatin nuclei fused with
      neurons, and there was an increase in vascularization. CONCLUSION: Three weeks
      after transplantation surgery, it was determined that iloprost maintained the
      viability of the graft tissue and probably prevented apoptosis, and facilitated
      the integration of the graft tissue into the host brain.

PMID- 21857591
TI  - Comparison of recovery after anesthesia with remifentanil infusion versus
      halothane in children undergoing strabismus surgery.
AB  - OBJECTIVE: To compare recovery after anesthesia with remifentanil infusion versus
      halothane for strabismus surgery METHODS: This study was performed from September
      2004 to March 2005 in Tabriz Nikookary Hospital, Tabriz, Iran on children aged 2
      12 years scheduled for strabismus surgery randomized into 2 groups of 25 patients
      each: the H group in which anesthesia was maintained with halothane and the R
      group in which anesthesia was maintained with remifentanil. RESULTS: There was no
      meaningful difference in extubation time after discontinuing drugs between the 2
      groups (p=0.14). However, there was a significant difference in the time of
      purposeful movements, proper oxygenation, consciousness, and discharge from the
      post anesthetic care unit between the 2 groups, all being shorter in group R.
      Also in group R, the time to spontaneous breathing return was longer, cases of
      neuromuscular reversal were fewer and cases of limb movements were more than
      group H. CONCLUSION: Maintenance of anesthesia with remifentanil in children aged
      2-12 years undergoing strabismus surgery provided desired hemodynamic status and
      shorter time of discharge criteria.

PMID- 21857592
TI  - High frequency of IgM antiphospholipid antibodies in young Iranian patients with
      stroke.
AB  - OBJECTIVE: To investigate the presence of IgG and IgM types of anticardiolipin
      (aCL) and antiphospholipid (aPL) antibodies in younger Iranian patients with
      ischemic stroke. METHODS: Both IgG and IgM types of aPL (cardiolipin, anti
      phosphatidyl inositol, anti phosphatidyl serine, anti phosphatidic acid and beta
      2-glycoprotein I [B2-GPI]) and aCL alone (cardiolipin and B2-GPI) were measured
      in 117 patients with ischemic stroke (aged <45 years) during an 18-month period
      from September 2002 to March 2004 in Al-Zahra Hospital, Isfahan, Iran. The
      demographic, clinical, and laboratory characteristics of patients with a positive
      titer were recorded. RESULTS: Seven men and 16 women (23 patients, 19.6%) had
      increased IgG types of aPL antibodies. Increased titers of IgM and IgG were found
      in 19 (82.6%) and 6 (26%) patients for aPL antibodies and in 15 (83.3%) and 8
      (44.4%) cases for aCL alone. CONCLUSION: Despite European studies, high titers of
      IgM aPL antibodies found in a large number of patients can be caused by the
      presence of unknown triggering factors (infections or poisons), that are more
      prevalent in developing countries compared to developed countries. This
      hypothesis remains to be investigated further.

PMID- 21857593
TI  - Human leukocyte antigen typing in Iraqi multiple sclerosis patients.
AB  - OBJECTIVE: To assess the relative frequency of human leukocyte antigen (HLA)
      class I and class II in Iraqi multiple sclerosis (MS) patients, and to ascertain
      whether they offer any etiologic or protective role. METHODS: We conducted this
      study in the Baghdad MS Clinic and Teaching Laboratory Institute, Medical City,
      Baghdad Teaching Hospital, Baghdad, Iraq from March to July 2004. We enrolled 44
      randomly selected MS patients and 69 healthy unrelated age- and sex-matched
      controls. We carried out HLA class I and class II typing on both groups using the
      microlymphocytotoxicity test. RESULTS: The HLA class I typing revealed no
      consistent association between MS and HLA-A and -Cw, while HLA-B5 and -B44 were
      found to possibly be risk factors for MS with odds ratio (OR) of 10.2 for -B5 and
      4.4 for -B44. The HLA-B35 may form a protective factor with OR of 0.1. The HLA
      class II typing revealed an etiologic risk for HLA-DR4 (OR=10.3) and a protective
      effect for HLA-DR2 (OR=0.3) and -DR7 (OR=0.2), and etiologic effect for -DQ1
      (OR=3.3) and -DQ3 (OR=3). CONCLUSION: The HLA DR4 carries the strongest
      association with MS in Iraqi patients. This study adds to the well-known
      diversity of HLA-allelic association of MS in different populations, and
      emphasizes the complexity of genetic susceptibility to MS.

PMID- 21857594
TI  - Orthostatic hypotension in Iranian patients with Parkinson's disease.
AB  - OBJECTIVE: To prospectively investigate the prevalence and clinical relevance of
      orthostatic hypotension (OH) in Parkinson's disease (PD) in Isfahan, Iran.
      METHODS: We investigated 150 consecutive patients with PD (42 women, 108 men) in
      Al-Zahra Hospital, Isfahan, Iran from January 2002 to January 2004. Blood
      pressure was measured first in a supine position following a rest of at least 10
      minutes, and then after 3 minutes of active standing. Data concerning the age,
      gender, duration of disease, and drug consumption were recorded in a
      questionnaire. RESULTS: Orthostatic hypotension in PD is more frequent in women,
      patients taking a higher dose of levodopa, in higher age groups, and patients
      with longer duration of the disease, however, a statistically significant
      difference was seen in the female group and patients taking a higher dose of
      levodopa. CONCLUSION: Orthostatic hypotension is mainly related to PD pathology
      and the clinical relevance of OH to gender, age, and disease duration may be due
      to the natural course for progression of human autonomic dysfunction during life.
      Higher doses of levodopa may increase the risk of OH.

PMID- 21857595
TI  - Assessment of autonomic function in patients with rheumatoid arthritis using
      spectral analysis and approximate entropy method.
AB  - OBJECTIVE: To assess the effect of rheumatoid arthritis (RA) on autonomic
      function of a group of RA patients in comparison with a normal control group by
      measuring the frequency gain response of the 2 groups. Also, to determine whether
      the duration of RA correlated with measures of heart rate variability signal
      (HRV) using an approximate entropy index (ApEn). METHODS: We evaluated 52
      patients with RA, and 51 matched healthy subjects at the Arthritis Center, Johns
      Hopkins Hospital, Maryland, United States during 2004 and 2005. We measured
      breathing at different rates, and the HRV signal derived from ECG. The auto-power
      and cross power spectra between HRV signal and breathing signal at different
      breathing rates was calculated, and the frequency gain response for both groups
      was obtained. The ApEn, described as a measure of regularity of HRV, was
      calculated for both patients with RA and the healthy control subjects. RESULTS:
      Both frequency gain response and ApEn measure were reduced in patients with RA in
      comparison with the control group. The power spectra of patients with RA showed a
      reduced high frequency (HF) value and higher low frequency for control subjects.
      However, the ApEn measure was significantly reduced in longer RA duration
      patients. CONCLUSION: These findings suggest that the spectral analysis of HRV
      signal using breathing at different frequencies may detect an unbalance of the
      autonomic system of patients with RA, especially with increasing the sympathetic
      activity (higher low frequency) and reducing the parasympathetic tone (reduced
      frequency gain response), which can lead to sudden death in patients with RA. The
      ApEn may be a marker of RA stage.

PMID- 21857596
TI  - Decreased handgrip strength and increased hip osteoporosis in patients with
      Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the causes of disability in the musculoskeletal system,
      and depression in patients with Alzheimer's disease (AD) and healthy controls.
      METHODS: A case-controlled study in which healthy elderly patients (n=56) and
      patients with AD (n=75) attending the Geriatric Rehabilitation Unit of Ankara
      Education and Research Hospital, Department of Physical Medicine and
      Rehabilitation were compared on several measures of disability including handgrip
      strength, knee x-rays graded for osteoarthritis, dual-energy x-ray absorptiometry
      results for osteoporosis, and depression scores in the training period of 2003
      2004. RESULTS: Handgrip strength values were significantly lower in patients with
      AD compared to the controls (19.4 versus 37 pounds force). Osteoporosis in the
      femoral neck was also more prominent in patients with AD compared to controls (T
      scores: -2.1 versus -1.2). Handgrip strength was moderately correlated with
      femoral neck T-scores (r=0.6, p=0.001). CONCLUSION: Strategies should be
      developed to protect patients with AD from osteoporosis and reduced muscle
      strength.

PMID- 21857597
TI  - Preoperative anxiety before elective surgery.
AB  - OBJECTIVE: To ascertain the preoperative anxiety level and different factors
      responsible in patients admitted for an elective surgical procedure in a tertiary
      care public hospital. METHODS: Anxiety levels were measured in admitted patients
      of the Civil Hospital, Karachi, Pakistan awaiting elective surgery from October
      to January 2006. In the afternoon preceding surgery, patients were asked to
      complete 2 visual analogue scales (VAS) regarding anxiety about the proposed
      surgery and anesthesia (range, 0 = 'not anxious at all' to 100 = 'extremely
      anxious'). They were then asked to select different factors responsible for their
      anxiety from a list. RESULTS: Mean anxiety score for surgery was 57.65+/-25.1 and
      for anesthesia was 38.14+/-26.05. There was a statistically significant high
      level of pre-operative anxiety in females as compared to males (p<0.01). The most
      common factors contributing to anxiety were concern about family in 173 (89.6%)
      patients, fear of complications in 168 (87%), results of operation in 159
      (82.4%), and postoperative pain in 152 (78.8%). Fifty-six percent of patients
      thought that their anxiety would be lessened by a detailed explanation regarding
      the operation and anesthesia. CONCLUSION: Our patients experience very high
      levels of preoperative anxiety. This can be easily measured in the preoperative
      period and allows detection of patients with high anxiety, encouraging
      appropriate steps to ameliorate this. Establishment of preoperative counseling
      clinics and properly informed consent taken before surgery will help in reducing
      preoperative anxiety.

PMID- 21857598
TI  - An unusual case of isolated trochlear nerve palsy.
AB  - Trochlear nerve palsy is rarely encountered in children and only 5% are truly
      isolated. Multiple sclerosis (MS) is also extremely uncommon in children. This
      report describes an otherwise healthy 10-year-old boy who presented with a 5-day
      history of vertical diplopia with associated dizziness, decreased appetite, and
      unsteadiness. He had no recent history of infection and no previous history of
      neurological symptoms. Ophthalmologic assessment revealed full ocular ductions
      and right hyperdeviation in primary gaze during alternate cover test. This
      hyperdeviation increased during left gaze, and right head tilt consistent with
      paresis of the right oblique muscle. Brain MRI revealed multiple well-defined
      hyperintense T2 lesions in the periventricular and subcortical white matter, and
      brainstem, suggestive of MS. His symptoms resolved after 2 weeks with no
      treatment. To conclude, isolated trochlear nerve palsy can be the initial
      clinical manifestation of childhood MS. Long term follow up is needed to confirm
      the diagnosis of MS.

PMID- 21857599
TI  - Tiagabine-induced non-convulsive status epilepticus in a patient without history
      of epilepsy.
AB  - Cases of non-convulsive status epilepticus (NCSE) induced by tiagabine (TGB) were
      occasionally reported. Almost all had a prior history of epilepsy. We describe
      here, the clinical and EEG findings in a patient, without history of seizures,
      who after the start of TGB developed NCSE. A 53-year-old man with history of
      paranoid schizophrenia, presented with "alteration of his mental state." Three
      weeks early, TGB was added to his psychiatric regimen. On the second day of
      admission, he became unresponsive with a blank stare. Concomitant EEG showed
      abundant sharp and slow wave complexes. The episode lasted for 4 hours and was
      aborted by the intravenous administration of lorazepam. The TGB was discontinued
      without recurrence of subsequent seizure activity. This case supports the
      contention that TGB can induce NCSE in subjects not previously known to have
      seizures.

PMID- 21857600
TI  - Vertebral scalloping in neurofibromatosis-1.
AB  - A 39-year-old male patient known to have neurofibromatosis-1, presented with
      sciatica and low back pain. At the age of 27, an MRI of the spine revealed
      widening of the lumbar canal due to posterior scalloping of the last 4 lumbar
      vertebrae. Repeat MRI and simple lateral lumbosacral plain film at the age of 39,
      revealed significant progression of the lumbosacral lesion. In view of the
      progression of the disease during the last 15 years, we opted for insertion of a
      lumbo-peritoneal (LP) shunt to decrease the CSF pressure, which is the most
      probable cause of scalloping. We shied away from lumbar fixation as we thought
      that this would not stop the vertebral erosion. The LP shunt affected good
      symptomatic and radiologic outcome over a 2-year follow up.

PMID- 21857601
TI  - MR imaging of multiple sclerosis simulating brain tumor.
AB  - Multiple sclerosis (MS) may sometimes present as a mass lesion that is clinically
      and radiologically indistinguishable from brain tumor. The initial recognition of
      such cases is essential to avoid a surgical intervention and supplementary
      treatment. Sometimes areas adjacent to a tumor may present similar
      histopathological features with non-neoplastic demyelinating lesions. Thus, the
      proper preparation of the specimen is the key for correct pathological diagnosis.
      We report a case of MS with large cranial involvement showing a mass effect. The
      operative procedure associated with medical treatment was performed, and a good
      result was obtained. Our case presentation and others in the literature suggest
      strategies for detecting MS presenting as a mass lesion.

PMID- 21857602
TI  - Solitary eosinophilic granuloma of the parietal bone in an adult patient.
AB  - Eosinophilic granuloma (EG) is a well-recognized benign form of Langerhans-cell
      histiocytosis. The estimated incidence of EG is 3-4 per million of the
      population. More patients are children and adolescents between the ages of 1-15
      years. In this report, we present an adult patient. A 37-year-old male was
      admitted with headache and right parietal swelling that was present for 2 months
      together with epileptic attacks. Cranial CT scan revealed a right parietal
      osteolytic lesion with large epidural and subcutaneous mass, causing brain
      compression. Total removal of the mass was carried out with cranioplasty.
      Histopathological examination disclosed Langerhans cell histiocytosis and
      immunohistochemical detection of S-100 antigen. At follow-up, he had no
      neurological deficits, and control CT was normal. For symptomatic solitary
      calvarial EG, surgical excision is the main treatment option. Surgical treatment
      is simple, quick, and allows histological diagnosis of the osteolytic lesions.

PMID- 21857603
TI  - Neurosurgical gossypiboma radiologically mimicking a lumbar abscess.
AB  - Lumbar discectomy is the most common operative technique at neurosurgery clinics
      around the world. The complications of lumbar disc operation include infections,
      dural tear, bleeding, vascular, and intestinal injuries. Infectious complications
      of lumbar disc surgery are superficial and profound tissue infections,
      meningitides, and epidural abscess. Although retained surgical sponges
      (gossypiboma) are well known intraoperative complications in other surgical
      branches, they have not been widely reported in neurosurgery. In this report, we
      present a case of retained surgical sponge at the operation site and discuss with
      the literature.

PMID- 21857604
TI  - Late-onset polyneuropathy due to malathion intoxication.

PMID- 21857605
TI  - Clinical and epidemiological aspects of headache in a neurology clinic in Babol,
      Northern Iran.

PMID- 21857606
TI  - The epidemiology of clinical neonatal seizures in Ramadi city.

PMID- 21857607
TI  - A young man with paresthesiae in the left hand.

PMID- 21857608
TI  - Obituary.

PMID- 21857609
TI  - Editorial message.

PMID- 21857610
TI  - Methylphenidate. An update on extended-release formulations.
AB  - Methylphenidate remains the mainstay of pharmacological management in attention
      deficit hyperactivity disorder (ADHD). Despite having been available for over
      half a century, methylphenidates original formulation has been modified with the
      main purpose of extending its duration of action. This article will present a
      brief review of how these new formulations vary and how these should be selected,
      considering the evidence available on their effectiveness and on the individual
      needs of the patient.

PMID- 21857611
TI  - Prevalence, symptomatology, and risk factors for depression among high school
      students in Saudi Arabia.
AB  - OBJECTIVE: To assess the prevalence and pattern of depression in a secondary
      school sample of Saudi Arabia adolescents. METHODS: Four hundred and ninety
      secondary school students, comprising 306 males (62.4%) and 184 females (37.6%),
      in the age group 16-20, were surveyed from January to May, 2005 in Taif, Saudi
      Arabia, using the Arabic Beck's Depression Inventory (BDI) by a team consisting
      of a psychiatrist and psychologist. RESULTS: The prevalence of depression
      according to the Beck Depression Inventory (CBDI) (cut-off point: 19) was 110
      (22.4%) for moderate (19-29), 36 (7.3%) for severe (30-40), and 18 (3.7%) as very
      severe (>40) in this study group, with a clear predominance of prevalence of
      depression in girls than in boys (1.5 times). Multivariate logistic regression
      analysis demonstrated that the most significant risk factors involved were:
      gender, birth order, history of psychiatric illness, history of relative loss,
      and familial history of chronic diseases. Factor analysis revealed that self
      criticalness, agitation, and loss of energy had the highest scores in the total
      sample. In the male subgroup, loss of energy, self-criticalness, punishment
      feeling, and agitation had the highest score while in the female subgroup, self
      criticalness, agitation, and crying had the highest scores. CONCLUSION: Our
      findings provide gender differences in the prevalence and presentation of
      depressive symptoms. The experience of stressful life events increases the risk
      of depression. Assessment using screening is recommended. The increased risk for
      the onset of depression in adolescents reinforces the importance of early
      recognition and intervention.

PMID- 21857612
TI  - Potentially serious Lamotrigine-related skin rash.
AB  - OBJECTIVE: To report our experience with lamotrigine (LTG)-related skin rash in
      children with epilepsy. METHODS: We identified a series of consecutive children
      with epilepsy treated with LTG prospectively over a 5-year period ending 1st
      October 2005 at King Abdul-Aziz University Hospital and King Faisal Specialist
      Hospital and Research Center, Jeddah, Kingdom of Saudi Arabia. RESULTS: Of 207
      children on LTG, 15 (7.2%) developed a skin rash with ages ranging between 3-12
      years (mean 7.5). We used LTG as monotherapy in 3/15 and as add on in 12/15,
      mostly (10/15) in addition to valproic acid (VPA). The rash was mild with
      complete recovery in 7 children (47%). The remaining 8 (3.9% of the total) had
      severe rash that necessitated admission to hospital. Seven out of these 8
      children were also receiving VPA. One child had superimposed secondary bacterial
      infection and admitted for intravenous antibiotics. Two children recovered slowly
      with extensive post-inflammatory hyperpigmentation. We diagnosed Stevens-Johnson
      syndrome in 5 children (2.4% of the total). One of these 5 children had
      progressive symptoms that evolved to toxic epidermal necrolysis. He required
      prolonged intensive care admission and developed sepsis with disseminated
      intravascular coagulopathy. He deteriorated despite supportive therapy, and died
      5 weeks after the initiation of LTG therapy. CONCLUSION: Lamotrigine is a novel
      antiepileptic drug with a favorable therapeutic profile and good tolerability.
      However, LTG-related skin rash is a potentially serious adverse event that should
      be carefully monitored. Although the risk is small, one should weigh this against
      the potential benefits, particularly in children on VPA.

PMID- 21857613
TI  - Anticardiolipin antibodies in stroke patients in Sudan. Appraisal of their
      significance in a region of high burden of endemic infections.
AB  - OBJECTIVE: To screen and evaluate the significance of anticardiolipin
      seroprevalence in patients with acute ischemic stroke, in patients with
      infectious disease, and in healthy subjects resident in Sudan, a tropical country
      endemic for several infectious diseases. METHODS: We conducted the study in
      Khartoum Teaching Hospital in Khartoum, Sudan between July 2003 and January 2005.
      We included 89 stroke cases, 30 infectious disease patients, and 30 asymptomatic
      healthy subjects. We estimated IgG and IgM anticardiolipin antibody titers in
      serum samples from all subjects in the 3 study categories at the time of hospital
      admission. RESULTS: We found a significantly higher prevalence of anticardiolipin
      antibodies in the stroke and infection groups compared to the healthy subjects.
      However, there was no significant difference in anticardiolipin seroprevalence
      between patients with stroke and patients with infectious disease. CONCLUSION:
      Caution is necessary when interpreting the presence of antiphospholipid
      antibodies as a stroke risk in patients harboring infection or living in places
      with high endemicity of infectious diseases.

PMID- 21857614
TI  - Tumor necrosis factor alpha serum levels and inflammatory response in acute
      ischemic stroke.
AB  - OBJECTIVE: To assess the implication of tumor necrosis factor alpha (TNF-alpha)
      and interleukine-6 (IL-6) in acute ischemic stroke and to correlate this with
      lesion size, vascular risk factors, and neurological impairment. METHODS: We
      included 70 patients consecutively admitted to the Department of 1st Neurology,
      Haydarpasa Numune Educational and Research Hospital, Istanbul, Turkey, between
      September 2001 and April 2002, with first-ever ischemic cerebral infarction
      within the first 24 hours from onset. The TNF-alpha, IL-6, fibrinogen, C-reactive
      protein, erythrocyte sedimentation rate (ESR) and leukocytes were determined in
      plasma on admission. Neurological impairment was evaluated with the modified
      Rankin Scale. RESULTS: We found higher baseline levels of TNF-alpha and IL-6 in
      the plasma of patients with acute ischemic stroke and neurological impairment in
      comparison to control subjects. In the large infarct group, TNF-alpha, IL-6, low
      density lipoprotein-cholesterol and fibrinogen were found significantly higher
      compared to the small infarct group. While an association between TNF-alpha and
      IL-6 values and lesion size were determined, no relation was found between
      localization and etiology. The TNF-alpha level was found to be in positive
      correlation with IL-6, fibrinogen, and ESR. The IL-6 level was found to be in
      positive correlation with ESR fibrinogen, and leukocytes. CONCLUSION:
      Inflammatory findings are associated with the early stage of ischemic stroke. The
      TNF-alpha and IL-6 were also higher in patients with clinical worsening. The
      release of proinflammatory cytokines after focal cerebral ischemia indicates a
      step leading to tissue necrosis or reflects the amount of ischemic brain injury,
      since the higher concentrations of TNF-alpha and IL-6 are found in patients with
      large infarctions.

PMID- 21857615
TI  - Assessment of nitrosative oxidative stress in patients with middle cerebral
      artery occlusion.
AB  - OBJECTIVE: To assess serum levels of nitric oxide and peroxynitrite in patients
      presenting with cerebral infarction resulting from middle cerebral artery
      occlusion, at 48 hours from stroke onset. METHODS: We conducted the study in the
      Department of Pharmacology and in cooperation with Al-Yarmouk Teaching Hospital
      and the Department of Medicine, College of Medicine, Al-Mustansiriya University,
      Baghdad, Iraq from October 2003 to May 2004. Twenty patients presented with
      neurological deficits of middle cerebral artery occlusion, and we also enrolled
      20 healthy individuals to serve as a control group. We obtained venous blood
      samples from each patient after 48 hours of stroke onset and each healthy
      individual. We determined the serum level of nitric oxide as well as
      peroxynitrite. RESULTS: Serum nitric oxide and peroxynitrite were significantly
      (p<0.001) higher in patients (103.9 +/- 40.2 umol and 2.7 +/- 0.6 umol) than in
      healthy individuals (53.3 +/- 20.7 umol and 2.3 +/- 0.2 umol). The formation of
      peroxynitrite directly correlated with nitric oxide in healthy individuals
      (r=0.84), and patients (r=0.514). CONCLUSION: Serum intermediate nitrogen
      species; nitric oxide and peroxynitrite were significantly increased after 48
      hours of stroke onset in patients with middle cerebral artery occlusion. The rate
      of peroxynitrite formation from nitric oxide was slightly increased.

PMID- 21857616
TI  - Comparison of neurological outcomes in patients undergoing conventional coronary
      artery bypass grafting, on-pump beating heart coronary bypass, and off-pump
      coronary bypass.
AB  - OBJECTIVE: To study the differences in the prevalence of neurological
      complications following coronary artery bypass (CAB) carried out by conventional,
      on-pump beating and off-pump techniques. METHODS: A retrospective analysis of all
      isolated coronary bypass operations (n=127) performed in King Fahad Cardiac
      Center, Riyadh over a period of one year starting from January 2005. Out of 127
      patients, 73 underwent conventional CAB graft (CABG), 33 patents on-pump beating
      heart coronary bypass, and 21 had off pump coronary bypass grafting (OPCAB). All
      patients had preoperative carotid scans and those who developed neurological
      complications underwent CT-brain and expert neuro-psychiatric assessment.
      RESULTS: Preoperative characteristics of patients in all 3 groups were similar.
      The bypass times in the conventional CABG group were significantly longer than
      the on-pump beating group. The maximum number of grafts was in the on-pump
      beating group, followed by the conventional CABG, and the least in the OPCAB
      group. Seven out of 73 cases in the conventional bypass group developed
      neurological events of various severities. Only one out of 33 patients developed
      acute confusional state in the on-pump beating group and no neurological events
      were noticed in 21 patients operated by the OPCAB technique. Low ejection
      fraction, preoperative congestive cardiac failure, non-elective surgery and
      preoperative catastrophic state were found to be significant risk factors
      independent of the bypass technique. CONCLUSION: This study shows no significant
      difference in the prevalence of neurological complications among different types
      of bypass surgery in our institution. There was a trend towards less neurological
      outcomes in the OPCAB and on-pump beating groups.

PMID- 21857617
TI  - Preoperative transcranial and carotid Doppler study in coronary artery bypass
      graft patients.
AB  - OBJECTIVE: To assess the correlation of postoperative neurologic complications
      with preoperative transcranial and carotid Doppler study findings of coronary
      artery bypass graft (CABG) patients. METHODS: In a descriptive, analytic, follow
      up study we prospectively studied 201 patients undergoing elective and isolated
      CABG surgery during a 12 month period from October 2003 to September 2004 at
      Madani Hospital of Tabriz Medical Sciences University, Iran. Neurologic
      examination, intracranial cerebral arterial study using transcranial Doppler
      (TCD) and carotid duplex were performed preoperatively. Intraoperative and
      postoperative complications were followed up for one month. RESULTS: Two hundred
      and one patients (158 male, 43 female) with a mean age of 57.29+/-9.67 were
      studied. Out of these, 131 patients had 3 coronary vessels disease, 64 had 2
      vessels, 5 had one vessel, and one patient had diffuse coronary disease. A TCD
      was performed in 183 patients and disclosed abnormalities in 22 patients and was
      normal in 161 cases. The total number of involved arteries was 34. Among 154
      carotid duplex studied patients, 102 had plaque, inducing <50% stenosis in 99, 50
      74% stenosis in one, and 75-90% stenosis in 2 cases. Postoperative neurologic
      complication occurred as follows: 4 stroke, 7 delirium, and 3 amnesia. One of the
      operated patients died. Nine of 161 patients with normal TCD (5.6%) and 5 of 22
      (22.7%) with intracranial cerebral arterial disease (ICAD) showed central nervous
      system (CNS) complications (p=0.015). There were significant correlations between
      number of involved cerebral arteries and post CABG CNS complications (p=0.0001),
      including stroke (p=0.007), and between diabetes mellitus history with these
      complications (p=0.012). CONCLUSION: Our results suggest that lCAD is an
      independent risk factor for CNS complications after CABG surgery. Hence, we
      recommend pre-CABG evaluation of the cerebral arteries by TCD, for the risk
      assessment of CABG surgery.

PMID- 21857618
TI  - Subclinical autonomic neuropathy in Saudi type 2 diabetic patients.
AB  - OBJECTIVE: To compare the results of autonomic function tests obtained from
      diabetic patients who had no symptoms or signs of somatic or autonomic neuropathy
      with those obtained from control subjects. METHODS: We studied 32 diabetic Saudi
      patients (17 males, 15 females) and 34 control subjects (17 of either gender) at
      King Khalid University Hospital, Riyadh, in the period 2004-2005. The mean age of
      patients was 50.3+/-5.04, and of controls was 49.9+/-5.86 years. In diabetics,
      the mean duration of the disease was 8.7+/-3.1 years (range 5-15 years), and the
      mean glycated hemoglobin was 7.76 +/-1.14. The same observer performed the
      autonomic function tests. RESULTS: In diabetics, the resting heart rate
      (beats/min) was 80.5+/-4.13, mean orthostasis ratio was 1.06+/-0.035, mean
      Valsalva ratio was 1.19+/-0.036, mean forced sinus arrhythmia was 12.66+/-0.8
      beats/min, mean diastolic blood pressure increase in response to isometric
      exercise was 13.03+/-1.36 mm Hg, and sympathetic skin response was present in
      only 18 (56.3%) out of 32 patients. These results were significantly different
      from the control group (p<0.001). CONCLUSION: Diabetic patients, with no symptoms
      or signs of neuropathy, can have impaired autonomic function. We consider this
      subclinical autonomic neuropathy.

PMID- 21857619
TI  - P50 variations in Behcet's patients without neurologic findings.
AB  - OBJECTIVE: In the present study, subclinical lesion involvement was investigated
      using the P50 component in Behcet's patients without neurological manifestation.
      METHODS: We performed this clinical research in Erciyes University, Faculty of
      Medicine between December 2000 and November 2001. The studies were carried out on
      18 Behcet's patients without neurologic findings and 18 volunteers for control.
      Standard Ag/AgCl electrodes in plastic cups were used for monopolar EEG
      derivations. They were attached with electrode paste and tape at the Cz (vertex)
      according to the 10-20 system. The auditory stimuli were delivered in pairs. The
      P50 waves, which may be taken from approximately 50 msec from the stimuli, were
      collected by computer system. Amplitudes and latencies of the P50 components were
      measured in the same system. RESULTS: This study showed that the suppression of
      P50 responses performed by the test stimuli, was significantly more decreased in
      Behcet's patients than the control subjects. CONCLUSION: The decrease of the
      suppression of the auditory P50 response to repeated stimuli reflects a deficit
      in the central nervous system's ability, such as attention, cognition, and
      sensory input in Behcet's patients and can be used as a neurophysiological marker
      in subclinical lesions in these patients.

PMID- 21857620
TI  - Quality of psychiatric referrals in Saudi Arabia. A structural equation modeling
      approach.
AB  - OBJECTIVE: This study seeks to model proposed causal relationships between the
      quality of psychiatric referral letters, and its indicators, linked to the
      features of the referred patient, referring physician, and practice setting.
      METHODS: This study was executed at Buraidah Mental Health Hospital, Saudi
      Arabia, in the year 2000-2002. Data regarding 18 independent variables underlying
      3 latent constructs and one dependent variable represented by quality of
      psychiatric referral letter score (outcome) was derived from patient files,
      physician training records, and 540 psychiatric referrals. Structural equation
      modeling was used to analyze the data for examining proposed causal relationships
      between the quality of psychiatric referral letters, and its potential
      predictors. RESULTS: The structural equation modeling analysis revealed a
      reasonably good fit of the proposed model to the data based on various fit
      indices. The tested model explained 67% of the variance in the quality of
      psychiatric referral letters. The referring physician characteristics
      (experience, education, and psychiatric training) and features of the referral
      setting (nature of setting and referral letters-administrative information) were
      highly significant indicators of quality of psychiatric referral letters, which
      in turn was negatively predicted by patient features including severity of the
      mental illness. CONCLUSION: Despite some caveats, the quality of psychiatric
      referral letters is accurately predicted by 3 latent constructs represented by
      referring physician skills, nature of the setting, and patient socio-clinical
      features.

PMID- 21857621
TI  - Sensation seeking behavior among schizophrenics.
AB  - OBJECTIVE: To compare sensation seeking between schizophrenic patients (and
      clinical subtypes of schizophrenia) according to criteria of DSM-IV-TR; and a
      healthy control group. Two hypotheses were assumed: 1. Sensation seeking in the
      control group is higher than schizophrenic patients. 2. The levels of sensation
      seeking are different among clinical subtypes of schizophrenia. METHODS: The
      sample comprised a study group of 69 schizophrenic inpatients at Raazy
      Psychiatric Center, Tehran, Iran in 2005 (10 males and 10 females for each of
      paranoid, undifferentiated and residual subtypes, and 9 males from disorganized
      subtype), and 50 randomly selected healthy people, the control group. To measure
      sensation seeking, the Zuckermann Sensation Seeking Scale, a 41-item
      questionnaire form, was used after evaluating its validity and reliability. After
      obtaining a weak or negative correlation, we omitted 9 questions, so that finally
      a 32-item questionnaire with highest reliability (Cronbach's alpha = 0.64),
      remained and was utilized. We used descriptive statistical methods and
      calculation of statistical indices, and Student t-test for independent groups to
      evaluate the research hypotheses. RESULTS: The first hypothesis was confirmed at
      a 99% significance level. The second hypothesis was rejected at a 95%
      significance level. CONCLUSION: We found a definite correlation between
      schizophrenia and a low level of sensation seeking. Accordingly, and since
      sensation seeking (as a part of temperament) has a strong genetic component, a
      low level of sensation seeking is probably an existing feature of schizophrenia.
      Assessing sensation seeking in high-risk populations (children or the siblings of
      schizophrenics) could be a practical attempt at prevention or immediate treatment
      of schizophrenia.

PMID- 21857622
TI  - Neurogenic stunned myocardium following hemorrhagic cerebral contusion.
AB  - Neurogenic stunned myocardium (NSM) is a well-known complication of
      subarachnoidal hemorrhage, but has been reported rarely in association with other
      central nervous system disorders. A case of NSM is described in a patient with
      hemorrhagic brain contusion associated with cerebral edema. An 18-year-old man
      was admitted with severe cranial trauma following a car roll-over. Six days after
      admission, he developed findings suggestive for NSM. The troponin T and creatine
      kinase-MB level were elevated and echocardiogram showed apical and
      inferoposterior hypokinesis and diffuse left ventricular akinesis with severely
      reduced ejection fraction (18%). Invasive measurements confirmed low cardiac
      output. His cardiac function resolved completely within 6 days after
      decompressive craniotomy. This case supports the presumed unifying role of the
      increased intracranial pressure, probably triggering a vigorous sympathetic
      outflow hyperactivity leading to NSM.

PMID- 21857623
TI  - Elevated cerebrospinal fluid b-2 microglobulin as a tumor marker in a patient
      with myeloma of the central nervous system.
AB  - Myeloma involvement of the nervous system is rare. Extensive literature review
      revealed only a few cases reported from different parts of the world. The
      presence of CNS symptoms and detection of plasma cells in the CSF is the usual
      basis of diagnosis. In addition, immunoelectrophoresis and immunofixation for
      detection of monoclonal protein confirm the diagnosis in some cases, while some
      authors used flow cytometry and cytogenetic studies on CSF. Reports of multiple
      myeloma also include unfavorable cytogenetic abnormalities of chromosome 13. We
      report a case with relapsed CNS multiple myeloma with the detection of elevated b
      2 microglobulin (b2M) as a tumor marker in the CSF.

PMID- 21857624
TI  - Orbital tumor presented systemic sarcoidosis.
AB  - Sarcoidosis is a granulomatous, multisystemic disorder of unknown origin usually
      affecting young Black-American adults. Bilateral hilar lymphadenopathy and skin
      or eyelid lesions are the most common symptoms noted. Except for lacrimal gland
      enlargement, orbital involvement with sarcoidosis is rare and is usually
      unilateral when it occurs. The aim of this article is to report an isolated case
      of sarcoidosis that initially presented as an orbital tumor, and to document the
      CT and MR appearance of the lesions.

PMID- 21857625
TI  - Takayasu arteritis diagnosed by 16-row multidetector CT angiography.
AB  - Takayasu's arteritis is a well-known systemic disease that involves the aorta,
      major aortic branches, and pulmonary arteries. Conventional catheter angiography
      remains the gold standard for disease diagnosis, in correlation with clinical
      data and laboratory findings. Multislice computed tomography angiography (MSCTA)
      has the advantage of non-invasively providing the angiographic data and combining
      morphological mural assessment with luminal evaluation. We present 2 such cases
      diagnosed by 16-slice MSCTA.

PMID- 21857626
TI  - Spontaneous regression of lumbar disc herniation.
AB  - We present 3 cases of spontaneous regression of lumbar herniated disc. The disc
      regression correlated with clinical improvement documented by MRI studies.
      Although the phenomenon of spontaneous disappearance of decrease in size of
      herniated disc fragments is well known, the exact mechanism underlying this
      process remains unclear. We discuss 3 possible explanations for disc regression:
      retraction into the vertebral space, dehydration/shrinkage, and resorption due to
      inflammatory reaction.

PMID- 21857627
TI  - Transforaminal epidural steroid injection for the treatment of severe back pain
      caused by cement leakage during kyphoplasty procedure.
AB  - Kyphoplasty is a minimally invasive procedure that is increasingly used to treat
      pain caused by compression fractures of vertebral bodies. A 56-year-old woman who
      had a compression fracture on the vertebral body of L5 vertebra was admitted to
      the Algology Department with a severe low back and leg pain. Kyphoplasty was
      planned for pain relief. She suffered severe pain in her back and left leg
      immediately after the procedure because of a leakage of injected cement through
      the fracture line. After injection of triamcinolone and bupivacaine
      transforaminally into the L5-S1 anterior epidural space, her pain complaints
      ended. If radicular pain symptoms caused by cement leakage are secondary to a
      chemically mediated non-cellular inflammatory reaction, transforaminal epidural
      steroid injection should be useful.

PMID- 21857628
TI  - Community-acquired Escherichia coli meningitis in a diabetic patient.

PMID- 21857630
TI  - Acardia acephalus fetus in a twin pregnancy.

PMID- 21857629
TI  - Unusual presentation of cryptococcal meningoencephalitis in a patient with renal
      transplant.

PMID- 21857631
TI  - A patient with recurrent deep vein thromboses and seizures.

PMID- 21857633
TI  - Inducing hibernation in the arctic ground squirrel.

PMID- 21857634
TI  - What dogs can teach us about bones.

PMID- 21857635
TI  - Nematodes win an 'evolutionary arms race' with fungi.

PMID- 21857636
TI  - Steps toward a universal flu vaccine.

PMID- 21857639
TI  - Authority to establish housing requirements.

PMID- 21857640
TI  - Authority to establish housing requirements. IACUC recommends, IO approves.

PMID- 21857641
TI  - Authority to establish housing requirements. Performance standards for housing.

PMID- 21857642
TI  - Authority to establish housing requirements. US regulations are the minimum.

PMID- 21857643
TI  - Transtracheal aspiration and infusion in the horse.
AB  - Transtracheal access enables researchers to obtain diagnostic samples from or
      infuse materials into the lower respiratory tract. This column describes
      transtracheal aspiration and infusion of horses.

PMID- 21857645
TI  - A user-friendly approach to cost accounting in laboratory animal facilities.
AB  - Cost accounting is an essential management activity for laboratory animal
      facility management. In this report, the author describes basic principles of
      cost accounting and outlines steps for carrying out cost accounting in laboratory
      animal facilities. Methods of post hoc cost accounting analysis for maximizing
      the efficiency of facility operations are also described.

PMID- 21857646
TI  - CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem
      cells.
AB  - Cancer stem cells or cancer initiating cells are believed to contribute to cancer
      recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with
      fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is
      only poorly understood. Here, we report miRNA expression profiles of glioblastoma
      stem cell-containing CD133(+) cell populations. We find that miR-9, miR-9(*)
      (referred to as miR-9/9(*)), miR-17 and miR-106b are highly abundant in CD133(+)
      cells. Furthermore, inhibition of miR-9/9(*) or miR-17 leads to reduced
      neurosphere formation and stimulates cell differentiation. Calmodulin-binding
      transcription activator 1 (CAMTA1) is a putative transcription factor, which
      induces the expression of the anti-proliferative cardiac hormone natriuretic
      peptide A (NPPA). We identify CAMTA1 as an miR-9/9(*) and miR-17 target. CAMTA1
      expression leads to reduced neurosphere formation and tumour growth in nude mice,
      suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1
      and NPPA expression correlate with patient survival. Our findings could provide a
      basis for novel strategies of glioblastoma therapy.

PMID- 21857647
TI  - A pH-regulated dimeric bouquet in the structure of von Willebrand factor.
AB  - At the acidic pH of the trans-Golgi and Weibel-Palade bodies (WPBs), but not at
      the alkaline pH of secretion, the C-terminal ~1350 residues of von Willebrand
      factor (VWF) zip up into an elongated, dimeric bouquet. Six small domains
      visualized here for the first time between the D4 and cystine-knot domains form a
      stem. The A2, A3, and D4 domains form a raceme with three pairs of opposed,
      large, flower-like domains. N-terminal VWF domains mediate helical tubule
      formation in WPBs and template N-terminal disulphide linkage between VWF dimers,
      to form ultralong VWF concatamers. The dimensions we measure in VWF at pH 6.2 and
      7.4, and the distance between tubules in nascent WPB, suggest that dimeric
      bouquets are essential for correct VWF dimer incorporation into growing tubules
      and to prevent crosslinking between neighbouring tubules. Further insights into
      the structure of the domains and flexible segments in VWF provide an overall view
      of VWF structure important for understanding both the biogenesis of ultralong
      concatamers at acidic pH and flow-regulated changes in concatamer conformation in
      plasma at alkaline pH that trigger hemostasis.

PMID- 21857648
TI  - LPA-producing enzyme PA-PLA1alpha regulates hair follicle development by
      modulating EGFR signalling.
AB  - Recent genetic studies of human hair disorders have suggested a critical role of
      lysophosphatidic acid (LPA) signalling in hair follicle development, mediated by
      an LPA-producing enzyme, phosphatidic acid-selective phospholipase A(1)alpha (PA
      PLA(1)alpha, also known as LIPH), and a recently identified LPA receptor, P2Y5
      (also known as LPA(6)). However, the underlying molecular mechanism is unknown.
      Here, we show that epidermal growth factor receptor (EGFR) signalling underlies
      LPA-induced hair follicle development. PA-PLA(1)alpha-deficient mice generated in
      this study exhibited wavy hairs due to the aberrant formation of the inner root
      sheath (IRS) in hair follicles, which resembled mutant mice defective in tumour
      necrosis factor alpha converting enzyme (TACE), transforming growth factor alpha
      (TGFalpha) and EGFR. PA-PLA(1)alpha was co-localized with TACE, TGFalpha and
      tyrosine-phosphorylated EGFR in the IRS. In PA-PLA(1)alpha-deficient hair
      follicles, cleaved TGFalpha and tyrosine-phosphorylated EGFR, as well as LPA,
      were significantly reduced. LPA, P2Y5 agonists and recombinant PA-PLA(1)alpha
      enzyme induced P2Y5- and TACE-mediated ectodomain shedding of TGFalpha through
      G12/13 pathway and consequent EGFR transactivation in vitro. These data
      demonstrate that a PA-PLA(1)alpha-LPA-P2Y5 axis regulates differentiation and
      maturation of hair follicles via a TACE-TGFalpha-EGFR pathway, thus underscoring
      the physiological importance of LPA-induced EGFR transactivation.

PMID- 21857649
TI  - Structure of the SSB-DNA polymerase III interface and its role in DNA
      replication.
AB  - Interactions between single-stranded DNA-binding proteins (SSBs) and the DNA
      replication machinery are found in all organisms, but the roles of these contacts
      remain poorly defined. In Escherichia coli, SSB's association with the chi
      subunit of the DNA polymerase III holoenzyme has been proposed to confer
      stability to the replisome and to aid delivery of primers to the lagging-strand
      DNA polymerase. Here, the SSB-binding site on chi is identified
      crystallographically and biochemical and cellular studies delineate the
      consequences of destabilizing the chi/SSB interface. An essential role for the
      chi/SSB interaction in lagging-strand primer utilization is not supported.
      However, sequence changes in chi that block complex formation with SSB lead to
      salt-dependent uncoupling of leading- and lagging-strand DNA synthesis and to a
      surprising obstruction of the leading-strand DNA polymerase in vitro, pointing to
      roles for the chi/SSB complex in replisome establishment and maintenance.
      Destabilization of the chi/SSB complex in vivo produces cells with temperature
      dependent cell cycle defects that appear to arise from replisome instability.

PMID- 21857650
TI  - Stabilizing the VE-cadherin-catenin complex blocks leukocyte extravasation and
      vascular permeability.
AB  - To determine whether leukocytes need to open endothelial cell contacts during
      extravasation, we decided to generate mice with strongly stabilized endothelial
      junctions. To this end, we replaced VE-cadherin genetically by a VE-cadherin
      alpha-catenin fusion construct. Such mice were completely resistant to the
      induction of vascular leaks by VEGF or histamine. Neutrophil or lymphocyte
      recruitment into inflamed cremaster, lung and skin were strongly inhibited in
      these mice, documenting the importance of the junctional route in vivo.
      Surprisingly, lymphocyte homing into lymph nodes was not inhibited. VE-cadherin
      alpha-catenin associated more intensely with the actin cytoskeleton as
      demonstrated by its membrane mobility and detergent extractability. Our results
      establish the junctional route as the main pathway for extravasating leukocytes
      in several, although not in all tissues. Furthermore, in these tissues,
      plasticity of the VE-cadherin-catenin complex is central for the leukocyte
      diapedesis mechanism.

PMID- 21857651
TI  - ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR
      alpha and PGC-1.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      that regulate genes involved in energy metabolism and inflammation. For
      biological activity, PPARs require cognate lipid ligands, heterodimerization with
      retinoic X receptors, and coactivation by PPAR-gamma coactivator-1alpha or PPAR
      gamma coactivator-1beta (PGC-1alpha or PGC-1beta, encoded by Ppargc1a and
      Ppargc1b, respectively). Here we show that lipolysis of cellular triglycerides by
      adipose triglyceride lipase (patatin-like phospholipase domain containing protein
      2, encoded by Pnpla2; hereafter referred to as Atgl) generates essential
      mediator(s) involved in the generation of lipid ligands for PPAR activation. Atgl
      deficiency in mice decreases mRNA levels of PPAR-alpha and PPAR-delta target
      genes. In the heart, this leads to decreased PGC-1alpha and PGC-1beta expression
      and severely disrupted mitochondrial substrate oxidation and respiration; this is
      followed by excessive lipid accumulation, cardiac insufficiency and lethal
      cardiomyopathy. Reconstituting normal PPAR target gene expression by
      pharmacological treatment of Atgl-deficient mice with PPAR-alpha agonists
      completely reverses the mitochondrial defects, restores normal heart function and
      prevents premature death. These findings reveal a potential treatment for the
      excessive cardiac lipid accumulation and often-lethal cardiomyopathy in people
      with neutral lipid storage disease, a disease marked by reduced or absent ATGL
      activity.

PMID- 21857652
TI  - In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen
      specific prothrombin activation.
AB  - Coagulase-positive Staphylococcus aureus (S. aureus) is the major causal pathogen
      of acute endocarditis, a rapidly progressing, destructive infection of the heart
      valves. Bacterial colonization occurs at sites of endothelial damage, where,
      together with fibrin and platelets, the bacteria initiate the formation of
      abnormal growths known as vegetations. Here we report that an engineered analog
      of prothrombin could be used to detect S. aureus in endocarditic vegetations via
      noninvasive fluorescence or positron emission tomography (PET) imaging. These
      prothrombin derivatives bound staphylocoagulase and intercalated into growing
      bacterial vegetations. We also present evidence for bacterial quorum sensing in
      the regulation of staphylocoagulase expression by S. aureus. Staphylocoagulase
      expression was limited to the growing edge of mature vegetations, where it was
      exposed to the host and co-localized with the imaging probe. When endocarditis
      was induced with an S. aureus strain with genetic deletion of coagulases,
      survival of mice improved, highlighting the role of staphylocoagulase as a
      virulence factor.

PMID- 21857653
TI  - Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating
      toxins.
AB  - The global prevalence of severe Clostridium difficile infection highlights the
      profound clinical significance of clostridial glucosylating toxins. Virulence is
      dependent on the autoactivation of a toxin cysteine protease, which is promoted
      by the allosteric cofactor inositol hexakisphosphate (InsP(6)). Host mechanisms
      that protect against such exotoxins are poorly understood. It is increasingly
      appreciated that the pleiotropic functions attributed to nitric oxide (NO),
      including host immunity, are in large part mediated by S-nitrosylation of
      proteins. Here we show that C. difficile toxins are S-nitrosylated by the
      infected host and that S-nitrosylation attenuates virulence by inhibiting toxin
      self-cleavage and cell entry. Notably, InsP(6)- and inositol pyrophosphate
      (InsP(7))-induced conformational changes in the toxin enabled host S
      nitrosothiols to transnitrosylate the toxin catalytic cysteine, which forms part
      of a structurally conserved nitrosylation motif. Moreover, treatment with
      exogenous InsP(6) enhanced the therapeutic actions of oral S-nitrosothiols in
      mouse models of C. difficile infection. Allostery in bacterial proteins has thus
      been successfully exploited in the evolutionary development of nitrosothiol-based
      innate immunity and may provide an avenue to new therapeutic approaches.

PMID- 21857654
TI  - CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus
      infection of nonhuman primates.
AB  - Vaccine-induced immunity to Ebola virus infection in nonhuman primates (NHPs) is
      marked by potent antigen-specific cellular and humoral immune responses; however,
      the immune mechanism of protection remains unknown. Here we define the immune
      basis of protection conferred by a highly protective recombinant adenovirus virus
      serotype 5 (rAd5) encoding Ebola virus glycoprotein (GP) in NHPs. Passive
      transfer of high-titer polyclonal antibodies from vaccinated Ebola virus-immune
      cynomolgus macaques to naive macaques failed to confer protection against
      disease, suggesting a limited role of humoral immunity. In contrast, depletion of
      CD3(+) T cells in vivo after vaccination and immediately before challenge
      eliminated immunity in two vaccinated macaques, indicating a crucial requirement
      for T cells in this setting. The protective effect was mediated largely by CD8(+)
      cells, as depletion of CD8(+) cells in vivo using the cM-T807 monoclonal antibody
      (mAb), which does not affect CD4(+) T cell or humoral immune responses, abrogated
      protection in four out of five subjects. These findings indicate that CD8(+)
      cells have a major role in rAd5-GP-induced immune protection against Ebola virus
      infection in NHPs. Understanding the immunologic mechanism of Ebola virus
      protection will facilitate the development of vaccines for Ebola and related
      hemorrhagic fever viruses in humans.

PMID- 21857655
TI  - The opposing roles of the transcription factor E2A and its antagonist Id3 that
      orchestrate and enforce the naive fate of T cells.
AB  - It is established that the transcription factor E2A and its antagonist Id3
      modulate the checkpoints consisting of the precursor to the T cell antigen
      receptor (pre-TCR) and the TCR. Here we demonstrate that Id3 expression was
      higher beyond the pre-TCR checkpoint, remained high in naive T cells and showed a
      bimodal pattern in the effector-memory population. We show how E2A promoted T
      lineage specification and how pre-TCR-mediated signaling affected E2A genome-wide
      occupancy. Thymi in Id3-deficient mice had aberrant development of effector
      memory cells, higher expression of the chemokine receptor CXCR5 and the
      transcriptional repressor Bcl-6 and, unexpectedly, T cell-B cell conjugates and B
      cell follicles. Collectively, our data show how E2A acted globally to orchestrate
      development into the T lineage and that Id3 antagonized E2A activity beyond the
      pre-TCR checkpoint to enforce the naive fate of T cells.

PMID- 21857656
TI  - Spatial gradients and multidimensional dynamics in a neural integrator circuit.
AB  - In a neural integrator, the variability and topographical organization of
      neuronal firing-rate persistence can provide information about the circuit's
      functional architecture. We used optical recording to measure the time constant
      of decay of persistent firing (persistence time) across a population of neurons
      comprising the larval zebrafish oculomotor velocity-to-position neural
      integrator. We found extensive persistence time variation (tenfold; coefficients
      of variation = 0.58-1.20) across cells in individual larvae. We also found that
      the similarity in firing between two neurons decreased as the distance between
      them increased and that a gradient in persistence time was mapped along the
      rostrocaudal and dorsoventral axes. This topography is consistent with the
      emergence of persistence time heterogeneity from a circuit architecture in which
      nearby neurons are more strongly interconnected than distant ones. Integrator
      circuit models characterized by multiple dimensions of slow firing-rate dynamics
      can account for our results.

PMID- 21857657
TI  - miR-124a is required for hippocampal axogenesis and retinal cone survival through
      Lhx2 suppression.
AB  - MicroRNA-124a (miR-124a) is the most abundant microRNA expressed in the
      vertebrate CNS. Despite past investigations into the role of miR-124a,
      inconsistent results have left the in vivo function of miR-124a unclear. We
      examined the in vivo function of miR-124a by targeted disruption of Rncr3
      (retinal non-coding RNA 3), the dominant source of miR-124a. Rncr3(-/-) mice
      exhibited abnormalities in the CNS, including small brain size, axonal mis
      sprouting of dentate gyrus granule cells and retinal cone cell death. We found
      that Lhx2 is an in vivo target mRNA of miR-124a. We also observed that LHX2
      downregulation by miR-124a is required for the prevention of apoptosis in the
      developing retina and proper axonal development of hippocampal neurons. These
      results suggest that miR-124a is essential for the maturation and survival of
      dentate gyrus neurons and retinal cones, as it represses Lhx2 translation.

PMID- 21857658
TI  - A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of
      absence epilepsy.
AB  - Cortico-thalamo-cortical circuits mediate sensation and generate neural network
      oscillations associated with slow-wave sleep and various epilepsies. Cortical
      input to sensory thalamus is thought to mainly evoke feed-forward synaptic
      inhibition of thalamocortical (TC) cells via reticular thalamic nucleus (nRT)
      neurons, especially during oscillations. This relies on a stronger synaptic
      strength in the cortico-nRT pathway than in the cortico-TC pathway, allowing the
      feed-forward inhibition of TC cells to overcome direct cortico-TC excitation. We
      found a systemic and specific reduction in strength in GluA4-deficient (Gria4(-/
      )) mice of one excitatory synapse of the rhythmogenic cortico-thalamo-cortical
      system, the cortico-nRT projection, and observed that the oscillations could
      still be initiated by cortical inputs via the cortico-TC-nRT-TC pathway. These
      results reveal a previously unknown mode of cortico-thalamo-cortical
      transmission, bypassing direct cortico-nRT excitation, and describe a mechanism
      for pathological oscillation generation. This mode could be active under other
      circumstances, representing a previously unknown channel of cortico-thalamo
      cortical information processing.

PMID- 21857659
TI  - Lateral habenula neurons signal errors in the prediction of reward information.
AB  - Humans and animals have the ability to predict future events, which they
      cultivate by continuously searching their environment for sources of predictive
      information. However, little is known about the neural systems that motivate this
      behavior. We hypothesized that information-seeking is assigned value by the same
      circuits that support reward-seeking, such that neural signals encoding reward
      prediction errors (RPEs) include analogous information prediction errors (IPEs).
      To test this, we recorded from neurons in the lateral habenula, a nucleus that
      encodes RPEs, while monkeys chose between cues that provided different chances to
      view information about upcoming rewards. We found that a subpopulation of lateral
      habenula neurons transmitted signals resembling IPEs, responding when reward
      information was unexpectedly cued, delivered or denied. These signals evaluated
      information sources reliably, even when the monkey's decisions did not. These
      neurons could provide a common instructive signal for reward-seeking and
      information-seeking behavior.

PMID- 21857660
TI  - Using simple donors to drive the equilibria of glycosyltransferase-catalyzed
      reactions.
AB  - We report that simple glycoside donors can drastically shift the equilibria of
      glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an
      endothermic to an exothermic process. To demonstrate the utility of this
      thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed
      synthesis of 22 sugar nucleotides from simple aromatic sugar donors, as well as
      the corresponding in situ formation of sugar nucleotides as a driving force in
      the context of glycosyltransferase-catalyzed reactions for small-molecule
      glycodiversification. These simple aromatic donors also enabled a general
      colorimetric assay for glycosyltransfer, applicable to drug discovery, protein
      engineering and other fundamental sugar nucleotide-dependent investigations. This
      study directly challenges the general notion that NDP-sugars are 'high-energy'
      sugar donors when taken out of their traditional biological context.

PMID- 21857661
TI  - Twisted Schiff base intermediates and substrate locale revise transaldolase
      mechanism.
AB  - We examined the catalytic cycle of transaldolase (TAL) from Thermoplasma
      acidophilum by cryocrystallography and were able to structurally characterize-
      for the first time, to our knowledge--different genuine TAL reaction
      intermediates. These include the Schiff base adducts formed between the catalytic
      lysine and the donor ketose substrates fructose-6-phosphate and sedoheptulose-7
      phosphate as well as the Michaelis complex with acceptor aldose erythrose-4
      phosphate. These structural snapshots necessitate a revision of the accepted
      reaction mechanism with respect to functional roles of active site residues, and
      they further reveal fundamental insights into the general structural features of
      enzymatic Schiff base intermediates and the role of conformational dynamics in
      enzyme catalysis, substrate binding and discrimination. A nonplanar arrangement
      of the substituents around the Schiff base double bond was observed, suggesting
      that a structurally encoded reactant-state destabilization is a driving force of
      catalysis. Protein dynamics and the intrinsic hydrogen-bonding pattern appear to
      be crucial for selective recognition and binding of ketose as first substrate.

PMID- 21857662
TI  - Multiple ligand-specific conformations of the beta2-adrenergic receptor.
AB  - Seven-transmembrane receptors (7TMRs), also called G protein-coupled receptors
      (GPCRs), represent the largest class of drug targets, and they can signal through
      several distinct mechanisms including those mediated by G proteins and the
      multifunctional adaptor proteins beta-arrestins. Moreover, several receptor
      ligands with differential efficacies toward these distinct signaling pathways
      have been identified. However, the structural basis and mechanism underlying this
      'biased agonism' remains largely unknown. Here, we develop a quantitative mass
      spectrometry strategy that measures specific reactivities of individual side
      chains to investigate dynamic conformational changes in the beta(2)-adrenergic
      receptor occupied by nine functionally distinct ligands. Unexpectedly, only a
      minority of residues showed reactivity patterns consistent with classical
      agonism, whereas the majority showed distinct patterns of reactivity even between
      functionally similar ligands. These findings demonstrate, contrary to two-state
      models for receptor activity, that there is significant variability in receptor
      conformations induced by different ligands, which has significant implications
      for the design of new therapeutic agents.

PMID- 21857663
TI  - An unusual dimeric structure and assembly for TLR4 regulator RP105-MD-1.
AB  - RP105-MD-1 modulates the TLR4-MD-2-mediated, innate immune response against
      bacterial lipopolysaccharide (LPS). The crystal structure of the bovine 1:1 RP105
      MD-1 complex bound to a putative endogenous lipid at 2.9 A resolution shares a
      similar overall architecture to its homolog TLR4-MD-2 but assembles into an
      unusual 2:2 homodimer that differs from any other known TLR-ligand assembly. The
      homodimer is assembled in a head-to-head orientation that juxtaposes the N
      terminal leucine-rich repeats (LRRs) of the two RP105 chains, rather than the
      usual tail-to-tail configuration of C-terminal LRRs in ligand-activated TLR
      dimers, such as TLR1-TRL2, TLR2-TLR6, TLR3-TLR3 and TLR4-TLR4. Another unusual
      interaction is mediated by an RP105-specific asparagine-linked glycan, which
      wedges MD-1 into the co-receptor binding concavity on RP105. This unique mode of
      assembly represents a new paradigm for TLR complexes and suggests a molecular
      mechanism for regulating LPS responses.

PMID- 21857664
TI  - Transfer RNA-mediated regulation of ribosome dynamics during protein synthesis.
AB  - Translocation of tRNAs through the ribosome during protein synthesis involves
      large-scale structural rearrangement of the ribosome and ribosome-bound tRNAs
      that is accompanied by extensive and dynamic remodeling of tRNA-ribosome
      interactions. How the rearrangement of individual tRNA-ribosome interactions
      influences tRNA movement during translocation, however, remains largely unknown.
      To address this question, we used single-molecule FRET to characterize the
      dynamics of ribosomal pretranslocation (PRE) complex analogs carrying either wild
      type or systematically mutagenized tRNAs. Our data reveal how specific tRNA
      ribosome interactions regulate the rate of PRE complex rearrangement into a
      critical, on-pathway translocation intermediate and how these interactions
      control the stability of the resulting configuration. Notably, our results
      suggest that the conformational flexibility of the tRNA molecule has a crucial
      role in directing the structural dynamics of the PRE complex during
      translocation.

PMID- 21857665
TI  - The structural basis of RNA-catalyzed RNA polymerization.
AB  - Early life presumably required polymerase ribozymes capable of replicating RNA.
      Known polymerase ribozymes best approximating such replicases use as their
      catalytic engine an RNA-ligase ribozyme originally selected from random RNA
      sequences. Here we report 3.15-A crystal structures of this ligase trapped in
      catalytically viable preligation states, with the 3'-hydroxyl nucleophile
      positioned for in-line attack on the 5'-triphosphate. Guided by metal- and
      solvent-mediated interactions, the 5'-triphosphate hooks into the major groove of
      the adjoining RNA duplex in an unanticipated conformation. Two phosphates and the
      nucleophile jointly coordinate an active-site metal ion. Atomic mutagenesis
      experiments demonstrate that active-site nucleobase and hydroxyl groups also
      participate directly in catalysis, collectively playing a role that in
      proteinaceous polymerases is performed by a second metal ion. Thus artificial
      ribozymes can use complex catalytic strategies that differ markedly from those of
      analogous biological enzymes.

PMID- 21857666
TI  - Mechanism of ubiquitylation by dimeric RING ligase RNF4.
AB  - Mammalian RNF4 is a dimeric RING ubiquitin E3 ligase that ubiquitylates poly
      SUMOylated proteins. We found that RNF4 bound ubiquitin-charged UbcH5a tightly
      but free UbcH5a weakly. To provide insight into the mechanism of RING-mediated
      ubiquitylation, we docked the UbcH5~ubiquitin thioester onto the RNF4 RING
      structure. This revealed that with E2 bound to one monomer of RNF4, the thioester
      linked ubiquitin could reach across the dimer to engage the other monomer. In
      this model, the 'Ile44 hydrophobic patch' of ubiquitin is predicted to engage a
      conserved tyrosine located at the dimer interface of the RING, and mutation of
      these residues blocked ubiquitylation activity. Thus, dimeric RING ligases are
      not simply inert scaffolds that bring substrate and E2-loaded ubiquitin into
      close proximity. Instead, they facilitate ubiquitin transfer by preferentially
      binding the E2~ubiquitin thioester across the dimer and activating the thioester
      bond for catalysis.

PMID- 21857667
TI  - The tumour suppressor L(3)mbt inhibits neuroepithelial proliferation and acts on
      insulator elements.
AB  - In Drosophila, defects in asymmetric cell division often result in the formation
      of stem-cell-derived tumours. Here, we show that very similar terminal brain
      tumour phenotypes arise through a fundamentally different mechanism. We
      demonstrate that brain tumours in l(3)mbt mutants originate from
      overproliferation of neuroepithelial cells in the optic lobes caused by
      derepression of target genes in the Salvador-Warts-Hippo (SWH) pathway. We use
      ChIP-sequencing to identify L(3)mbt binding sites and show that L(3)mbt binds to
      chromatin insulator elements. Mutating l(3)mbt or inhibiting expression of the
      insulator protein gene mod(mdg4) results in upregulation of SWH pathway
      reporters. As l(3)mbt tumours are rescued by mutations in bantam or yorkie or by
      overexpression of Expanded, the deregulation of SWH pathway target genes is an
      essential step in brain tumour formation. Therefore, very different primary
      defects result in the formation of brain tumours, which behave quite similarly in
      their advanced stages.

PMID- 21857668
TI  - miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a
      cell fate threshold.
AB  - Patterns of cell fates generated by morphogens are critically important for
      normal development; however, the mechanisms by which graded morphogen signals are
      converted into all-or-none cell fate responses are incompletely understood. In
      the Drosophila ovary, high and sustained levels of the secreted morphogen
      Unpaired (Upd) specify the migratory border-cell population by activating the
      signal transducer and activator of transcription (STAT). A lower or transient
      level of STAT activity specifies a non-migratory population of follicle cells.
      Here we identify miR-279 as a component of a feedback pathway that further
      dampens the response in cells with low levels of JAK/STAT activity. miR-279
      directly repressed STAT, and loss of miR-279 mimicked STAT gain-of-function or
      loss of Apontic (Apt), a known feedback inhibitor of STAT. Apt was essential for
      miR-279 expression in non-migratory follicle cells, whereas another STAT target,
      Ken and Barbie (Ken), downregulated miR-279 in border cells. Mathematical
      modelling and simulations of this regulatory circuit including miR-279, Apt and
      Ken supported key roles for miR-279 and Apt in generating threshold responses to
      the Upd gradient.

PMID- 21857669
TI  - In vitro generation of human cells with cancer stem cell properties.
AB  - Cancer stem cells (CSCs) have been implicated in the maintenance and progression
      of several types of cancer. The origin and cellular properties of human CSCs are
      poorly characterized. Here we show that CSC-like cells can be generated in vitro
      by oncogenic reprogramming of human somatic cells during neoplastic
      transformation. We find that in vitro transformation confers stem-cell properties
      to primary differentiated fibroblasts, including the ability to self-renew and to
      differentiate along multiple lineages. Tumours induced by transformed fibroblasts
      are hierarchically organized, and the cells that act as CSCs to initiate and
      maintain tumour growth are marked by the stage-specific embryonic antigen SSEA-1.
      Heterogeneous lineages of cancer cells in the bulk of the tumour arise through
      differentiation of SSEA-1(+) fibroblasts, and differentiation is associated with
      loss of tumorigenic potential. These findings establish an experimental system to
      characterize cellular and molecular properties of human CSCs and demonstrate that
      somatic cells have the potential to de-differentiate and acquire properties of
      CSCs.

PMID- 21857670
TI  - aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during
      asymmetric division.
AB  - The position of the mitotic spindle controls the plane of cell cleavage and
      determines whether polarized cells divide symmetrically or asymmetrically. In
      animals, an evolutionarily conserved pathway of LIN-5 (homologues: Mud and NuMA),
      GPR-1/2 (homologues: Pins, LGN, AGS-3) and Galpha mediates spindle positioning,
      and acts downstream of the conserved PAR-3-PAR-6-aPKC polarity complex. However,
      molecular interactions between polarity proteins and LIN-5-GPR-Galpha remain to
      be identified. Here we describe a quantitative mass spectrometry approach for in
      vivo identification of protein kinase substrates. Applying this strategy to
      Caenorhabditis elegans embryos, we found that depletion of the polarity kinase
      PKC-3 results in markedly decreased levels of phosphorylation of a cluster of
      four LIN-5 serine residues. These residues are directly phosphorylated by PKC-3
      in vitro. Phospho-LIN-5 co-localizes with PKC-3 at the anterior cell cortex and
      temporally coincides with a switch from anterior- to posterior-directed spindle
      movements in the one-cell embryo. LIN-5 mutations that prevent phosphorylation
      increase the extent of anterior-directed spindle movements, whereas
      phosphomimetic mutations decrease spindle migration. Our results indicate that
      anterior-located PKC-3 inhibits cortical microtubule pulling forces through
      direct phosphorylation of LIN-5. This molecular interaction between polarity and
      spindle-positioning proteins may be used broadly in cell cleavage plane
      determination.

PMID- 21857671
TI  - DNA-damage response and repair activities at uncapped telomeres depend on RNF8.
AB  - Loss of telomere protection causes natural chromosome ends to become recognized
      by DNA-damage response and repair proteins. These events result in ligation of
      chromosome ends with dysfunctional telomeres, thereby causing chromosomal
      aberrations on cell division. The control of these potentially dangerous events
      at deprotected chromosome ends with their unique telomeric chromatin
      configuration is poorly understood. In particular, it is unknown to what extent
      bulky modification of telomeric chromatin is involved. Here we show that uncapped
      telomeres accumulate ubiquitylated histone H2A in a manner dependent on the E3
      ligase RNF8. The ability of RNF8 to ubiquitylate telomeric chromatin is
      associated with its capacity to facilitate accumulation of both 53BP1 and phospho
      ATM at uncapped telomeres and to promote non-homologous end-joining of
      deprotected chromosome ends. In line with the detrimental effect of RNF8 on
      uncapped telomeres, depletion of RNF8, as well as of the E3 ligase RNF168,
      reduces telomere-induced genome instability. This indicates that, besides
      suppressing tumorigenesis by mediating repair of DNA double-strand breaks, RNF8
      and RNF168 might enhance cancer development by aggravating telomere-induced
      genome instability.

PMID- 21857672
TI  - Site-specific integration and tailoring of cassette design for sustainable gene
      transfer.
AB  - Integrative gene transfer methods are limited by variable transgene expression
      and by the consequences of random insertional mutagenesis that confound
      interpretation in gene-function studies and may cause adverse events in gene
      therapy. Site-specific integration may overcome these hurdles. Toward this goal,
      we studied the transcriptional and epigenetic impact of different transgene
      expression cassettes, targeted by engineered zinc-finger nucleases to the CCR5
      and AAVS1 genomic loci of human cells. Analyses performed before and after
      integration defined features of the locus and cassette design that together allow
      robust transgene expression without detectable transcriptional perturbation of
      the targeted locus and its flanking genes in many cell types, including primary
      human lymphocytes. We thus provide a framework for sustainable gene transfer in
      AAVS1 that can be used for dependable genetic manipulation, neutral marking of
      the cell and improved safety of therapeutic applications, and demonstrate its
      feasibility by rapidly generating human lymphocytes and stem cells carrying
      targeted and benign transgene insertions.

PMID- 21857673
TI  - Long-range spin Seebeck effect and acoustic spin pumping.
AB  - Imagine that a metallic wire is attached to a part of a large insulator, which
      itself exhibits no magnetization. It seems impossible for electrons in the wire
      to register where the wire is positioned on the insulator. Here we found that,
      using a Ni81Fe19/Pt bilayer wire on an insulating sapphire plate, electrons in
      the wire recognize their position on the sapphire. Under a temperature gradient
      in the sapphire, surprisingly, the voltage generated in the Pt layer is shown to
      reflect the wire position, although the wire is isolated both electrically and
      magnetically. This non-local voltage is due to the coupling of spins and phonons:
      the only possible carrier of information in this system. We demonstrate this
      coupling by directly injecting sound waves, which realizes the acoustic spin
      pumping. Our finding provides a persuasive answer to the long-range nature of the
      spin Seebeck effect, and it opens the door to 'acoustic spintronics' in which
      sound waves are exploited for constructing spin-based devices.

PMID- 21857674
TI  - Interface-induced room-temperature multiferroicity in BaTiO3.
AB  - Multiferroic materials possess two or more ferroic orders but have not been
      exploited in devices owing to the scarcity of room-temperature examples. Those
      that are ferromagnetic and ferroelectric have potential applications in multi
      state data storage if the ferroic orders switch independently, or in electric
      field controlled spintronics if the magnetoelectric coupling is strong. Future
      applications could also exploit toroidal moments and optical effects that arise
      from the simultaneous breaking of time-reversal and space-inversion symmetries.
      Here, we use soft X-ray resonant magnetic scattering and piezoresponse force
      microscopy to reveal that, at the interface with Fe or Co, ultrathin films of the
      archetypal ferroelectric BaTiO3 simultaneously possess a magnetization and a
      polarization that are both spontaneous and hysteretic at room temperature. Ab
      initio calculations of realistic interface structures provide insight into the
      origin of the induced moments and bring support to this new approach for creating
      room-temperature multiferroics.

PMID- 21857675
TI  - A 3.90 V iron-based fluorosulphate material for lithium-ion batteries
      crystallizing in the triplite structure.
AB  - Li-ion batteries have empowered consumer electronics and are now seen as the best
      choice to propel forward the development of eco-friendly (hybrid) electric
      vehicles. To enhance the energy density, an intensive search has been made for
      new polyanionic compounds that have a higher potential for the Fe2+/Fe3+ redox
      couple. Herein we push this potential to 3.90 V in a new polyanionic material
      that crystallizes in the triplite structure by substituting as little as 5 atomic
      per cent of Mn for Fe in Li(Fe(1-delta)Mn(delta))SO4F. Not only is this the
      highest voltage reported so far for the Fe2+/Fe3+ redox couple, exceeding that of
      LiFePO4 by 450 mV, but this new triplite phase is capable of reversibly releasing
      and reinserting 0.7-0.8 Li ions with a volume change of 0.6% (compared with 7 and
      10% for LiFePO4 and LiFeSO4F respectively), to give a capacity of ~125 mA h g-1.

PMID- 21857676
TI  - Evolution and control of oxygen order in a cuprate superconductor.
AB  - The disposition of defects in metal oxides is a key attribute exploited for
      applications from fuel cells and catalysts to superconducting devices and
      memristors. The most typical defects are mobile excess oxygens and oxygen
      vacancies, which can be manipulated by a variety of thermal protocols as well as
      optical and d.c. electric fields. Here we report the X-ray writing of high
      quality superconducting regions, derived from defect ordering, in the
      superoxygenated layered cuprate, La2CuO(4+y). Irradiation of a poor
      superconductor prepared by rapid thermal quenching results first in the growth of
      ordered regions, with an enhancement of superconductivity becoming visible only
      after a waiting time, as is characteristic of other systems such as
      ferroelectrics, where strain must be accommodated for order to become extended.
      However, in La2CuO(4+y), we are able to resolve all aspects of the growth of
      (oxygen) intercalant order, including an extraordinary excursion from low to high
      and back to low anisotropy of the ordered regions. We can also clearly associate
      the onset of high-quality superconductivity with defect ordering in two
      dimensions. Additional experiments with small beams demonstrate a photoresist
      free, single-step strategy for writing functional materials.

PMID- 21857678
TI  - In vivo and in vitro tracking of erosion in biodegradable materials using non
      invasive fluorescence imaging.
AB  - The design of erodible biomaterials relies on the ability to program the in vivo
      retention time, which necessitates real-time monitoring of erosion. However, in
      vivo performance cannot always be predicted by traditional determination of in
      vitro erosion, and standard methods sacrifice samples or animals, preventing
      sequential measures of the same specimen. We harnessed non-invasive fluorescence
      imaging to sequentially follow in vivo material-mass loss to model the
      degradation of materials hydrolytically (PEG:dextran hydrogel) and enzymatically
      (collagen). Hydrogel erosion rates in vivo and in vitro correlated, enabling the
      prediction of in vivo erosion of new material formulations from in vitro data.
      Collagen in vivo erosion was used to infer physiologic in vitro conditions that
      mimic erosive in vivo environments. This approach enables rapid in vitro
      screening of materials, and can be extended to simultaneously determine drug
      release and material erosion from a drug-eluting scaffold, or cell viability and
      material fate in tissue-engineering formulations.

PMID- 21857679
TI  - MicroRNAs can generate thresholds in target gene expression.
AB  - MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that
      repress gene expression in a sequence-dependent manner. We performed single-cell
      measurements using quantitative fluorescence microscopy and flow cytometry to
      monitor a target gene's protein expression in the presence and absence of
      regulation by miRNA. We find that although the average level of repression is
      modest, in agreement with previous population-based measurements, the repression
      among individual cells varies dramatically. In particular, we show that
      regulation by miRNAs establishes a threshold level of target mRNA below which
      protein production is highly repressed. Near this threshold, protein expression
      responds sensitively to target mRNA input, consistent with a mathematical model
      of molecular titration. These results show that miRNAs can act both as a switch
      and as a fine-tuner of gene expression.

PMID- 21857680
TI  - Solution structure of a minor and transiently formed state of a T4 lysozyme
      mutant.
AB  - Proteins are inherently plastic molecules, whose function often critically
      depends on excursions between different molecular conformations (conformers).
      However, a rigorous understanding of the relation between a protein's structure,
      dynamics and function remains elusive. This is because many of the conformers on
      its energy landscape are only transiently formed and marginally populated (less
      than a few per cent of the total number of molecules), so that they cannot be
      individually characterized by most biophysical tools. Here we study a lysozyme
      mutant from phage T4 that binds hydrophobic molecules and populates an excited
      state transiently (about 1 ms) to about 3% at 25  degrees C (ref. 5). We show
      that such binding occurs only via the ground state, and present the atomic-level
      model of the 'invisible', excited state obtained using a combined strategy of
      relaxation-dispersion NMR (ref. 6) and CS-Rosetta model building that
      rationalizes this observation. The model was tested using structure-based design
      calculations identifying point mutants predicted to stabilize the excited state
      relative to the ground state. In this way a pair of mutations were introduced,
      inverting the relative populations of the ground and excited states and altering
      function. Our results suggest a mechanism for the evolution of a protein's
      function by changing the delicate balance between the states on its energy
      landscape. More generally, they show that our approach can generate and validate
      models of excited protein states.

PMID- 21857681
TI  - A stress response pathway regulates DNA damage through beta2-adrenoreceptors and
      beta-arrestin-1.
AB  - The human mind and body respond to stress, a state of perceived threat to
      homeostasis, by activating the sympathetic nervous system and secreting the
      catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response.
      The stress response is generally transient because its accompanying effects (for
      example, immunosuppression, growth inhibition and enhanced catabolism) can be
      harmful in the long term. When chronic, the stress response can be associated
      with disease symptoms such as peptic ulcers or cardiovascular disorders, and
      epidemiological studies strongly indicate that chronic stress leads to DNA
      damage. This stress-induced DNA damage may promote ageing, tumorigenesis,
      neuropsychiatric conditions and miscarriages. However, the mechanisms by which
      these DNA-damage events occur in response to stress are unknown. The stress
      hormone adrenaline stimulates beta(2)-adrenoreceptors that are expressed
      throughout the body, including in germline cells and zygotic embryos. Activated
      beta(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase
      A (PKA), followed by the recruitment of beta-arrestins, which desensitize G
      protein signalling and function as signal transducers in their own right. Here we
      elucidate a molecular mechanism by which beta-adrenergic catecholamines, acting
      through both Gs-PKA and beta-arrestin-mediated signalling pathways, trigger DNA
      damage and suppress p53 levels respectively, thus synergistically leading to the
      accumulation of DNA damage. In mice and in human cell lines, beta-arrestin-1
      (ARRB1), activated via beta(2)-adrenoreceptors, facilitates AKT-mediated
      activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by
      acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in
      Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the
      thymus, an organ that responds prominently to acute or chronic stress, and in the
      testes, in which paternal stress may affect the offspring's genome. Our results
      highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and
      reveal how DNA damage may accumulate in response to chronic stress.

PMID- 21857682
TI  - Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2
      protein.
AB  - Rapid and efficient removal of apoptotic cells by phagocytes is important during
      development, tissue homeostasis and in immune responses. Efficient clearance
      depends on the capacity of a single phagocyte to ingest multiple apoptotic cells
      successively, and to process the corpse-derived cellular material. However, the
      factors that influence continued clearance by phagocytes are not known. Here we
      show that the mitochondrial membrane potential of the phagocyte critically
      controls engulfment capacity, with lower potential enhancing engulfment and vice
      versa. The mitochondrial membrane protein Ucp2, which acts to lower the
      mitochondrial membrane potential, was upregulated in phagocytes engulfing
      apoptotic cells. Loss of Ucp2 reduced phagocytic capacity, whereas Ucp2
      overexpression enhanced engulfment. Mutational and pharmacological studies
      indicated a direct role for Ucp2-mediated mitochondrial function in phagocytosis.
      Macrophages from Ucp2-deficient mice were impaired in phagocytosis in vitro, and
      Ucp2-deficient mice showed profound in vivo defects in clearing dying cells in
      the thymus and testes. Collectively, these data indicate that mitochondrial
      membrane potential and Ucp2 are key molecular determinants of apoptotic cell
      clearance. As Ucp2 is linked to metabolic diseases and atherosclerosis, this
      newly discovered role for Ucp2 in apoptotic cell clearance has implications for
      the complex aetiology and pathogenesis of these diseases.

PMID- 21857684
TI  - Solution-processed core-shell nanowires for efficient photovoltaic cells.
AB  - Semiconductor nanowires are promising for photovoltaic applications, but, so far,
      nanowire-based solar cells have had lower efficiencies than planar cells made
      from the same materials, even allowing for the generally lower light absorption
      of nanowires. It is not clear, therefore, if the benefits of the nanowire
      structure, including better charge collection and transport and the possibility
      of enhanced absorption through light trapping, can outweigh the reductions in
      performance caused by recombination at the surface of the nanowires and at p-n
      junctions. Here, we fabricate core-shell nanowire solar cells with open-circuit
      voltage and fill factor values superior to those reported for equivalent planar
      cells, and an energy conversion efficiency of ~5.4%, which is comparable to that
      of equivalent planar cells despite low light absorption levels. The device is
      made using a low-temperature solution-based cation exchange reaction that creates
      a heteroepitaxial junction between a single-crystalline CdS core and single
      crystalline Cu2S shell. We integrate multiple cells on single nanowires in both
      series and parallel configurations for high output voltages and currents,
      respectively. The ability to produce efficient nanowire-based solar cells with a
      solution-based process and Earth-abundant elements could significantly reduce
      fabrication costs relative to existing high-temperature bulk material approaches.

PMID- 21857683
TI  - Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and
      ALS/dementia.
AB  - Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal disorder
      caused by motor-neuron degeneration in the brain and spinal cord. Most cases of
      ALS are sporadic but about 5-10% are familial. Mutations in superoxide dismutase
      1 (SOD1), TAR DNA-binding protein (TARDBP, also known as TDP43) and fused in
      sarcoma (FUS, also known as translocated in liposarcoma (TLS)) account for
      approximately 30% of classic familial ALS. Mutations in several other genes have
      also been reported as rare causes of ALS or ALS-like syndromes. The causes of the
      remaining cases of familial ALS and of the vast majority of sporadic ALS are
      unknown. Despite extensive studies of previously identified ALS-causing genes,
      the pathogenic mechanism underlying motor-neuron degeneration in ALS remains
      largely obscure. Dementia, usually of the frontotemporal lobar type, may occur in
      some ALS cases. It is unclear whether ALS and dementia share common aetiology and
      pathogenesis in ALS/dementia. Here we show that mutations in UBQLN2, which
      encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited,
      chromosome-X-linked ALS and ALS/dementia. We describe novel ubiquilin 2 pathology
      in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or
      without UBQLN2 mutations. Ubiquilin 2 is a member of the ubiquilin family, which
      regulates the degradation of ubiquitinated proteins. Functional analysis showed
      that mutations in UBQLN2 lead to an impairment of protein degradation. Therefore,
      our findings link abnormalities in ubiquilin 2 to defects in the protein
      degradation pathway, abnormal protein aggregation and neurodegeneration,
      indicating a common pathogenic mechanism that can be exploited for therapeutic
      intervention.

PMID- 21857685
TI  - A single synthetic small molecule that generates force against a load.
AB  - Some biomolecules are able to generate directional forces by rectifying random
      thermal motions. This allows these molecular machines to perform mechanical tasks
      such as intracellular cargo transport or muscle contraction in plants and
      animals. Although some artificial molecular machines have been synthesized and
      used collectively to perform mechanical tasks, so far there have been no direct
      measurements of mechanical processes at the single-molecule level. Here we report
      measurements of the mechanical work performed by a synthetic molecule less than 5
      nm long. We show that biased Brownian motion of the sub-molecular components in a
      hydrogen-bonded [2]rotaxane-a molecular ring threaded onto a molecular axle-can
      be harnessed to generate significant directional forces. We used the cantilever
      of an atomic force microscope to apply a mechanical load to the ring during
      single-molecule pulling-relaxing cycles. The ring was pulled along the axle, away
      from the thermodynamically favoured binding site, and was then found to travel
      back to this site against an external load of 30 pN. Using fluctuation theorems,
      we were able to relate measurements of the work done at the level of individual
      rotaxane molecules to the free-energy change as previously determined from
      ensemble measurements. The results show that individual rotaxanes can generate
      directional forces of similar magnitude to those generated by natural molecular
      machines.

PMID- 21857686
TI  - Self-assembly of self-limiting monodisperse supraparticles from polydisperse
      nanoparticles.
AB  - Nanoparticles are known to self-assemble into larger structures through growth
      processes that typically occur continuously and depend on the uniformity of the
      individual nanoparticles. Here, we show that inorganic nanoparticles with non
      uniform size distributions can spontaneously assemble into uniformly sized
      supraparticles with core-shell morphologies. This self-limiting growth process is
      governed by a balance between electrostatic repulsion and van der Waals
      attraction, which is aided by the broad polydispersity of the nanoparticles. The
      generic nature of the interactions creates flexibility in the composition, size
      and shape of the constituent nanoparticles, and leads to a large family of self
      assembled structures, including hierarchically organized colloidal crystals.

PMID- 21857687
TI  - Photocurrent mapping of near-field optical antenna resonances.
AB  - An increasing number of photonics applications make use of nanoscale optical
      antennas that exhibit a strong, resonant interaction with photons of a specific
      frequency. The resonant properties of such antennas are conventionally
      characterized by far-field light-scattering techniques. However, many
      applications require quantitative knowledge of the near-field behaviour, and
      existing local field measurement techniques provide only relative, rather than
      absolute, data. Here, we demonstrate a photodetector platform that uses a silicon
      on-insulator substrate to spectrally and spatially map the absolute values of
      enhanced fields near any type of optical antenna by transducing local electric
      fields into photocurrent. We are able to quantify the resonant optical and
      materials properties of nanoscale (~50 nm) and wavelength-scale (~1 um) metallic
      antennas as well as high-refractive-index semiconductor antennas. The data agree
      well with light-scattering measurements, full-field simulations and intuitive
      resonator models.

PMID- 21857688
TI  - Stromal targeted therapy in bone metastatic prostate cancer: promise delivered.

PMID- 21857691
TI  - Triangle orientation discrimination performance model for a multiband IR imaging
      system with human vision.
AB  - In support of multiband imaging system performance forecasting, an equation-based
      triangle orientation discrimination (TOD) model is developed. Specifically, with
      the characteristic of the test pattern related to spectrum, the mathematical
      equations for predicting the TOD threshold of the system with distributed fusion
      architecture in the IR spectrum band are derived based on human vision with the
      "k/N" fusion rule, with emphasis on the impacts of fusion on the threshold.
      Furthermore, a figure of merit Q related to the TOD calculation results is
      introduced to analyze the relation of the discrimination performance of multiband
      imaging system to the size and the spectral difference of test pattern. The
      preliminary validation with the experiment results suggests that our proposed
      model can provide a reasonable prediction of the performance for a multiband
      imaging system.

PMID- 21857689
TI  - Folate and vitamin B12 in idiopathic male infertility.
AB  - Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been
      associated with idiopathic male infertility, few studies have examined other
      folate-related metabolites and genes. We investigated whether idiopathic male
      infertility is associated with variants in folate, vitamin B(12) (B12) and total
      homocysteine (tHcy)-related genes and measured these metabolites in blood. We
      conducted a case-control study that included 153 men with idiopathic infertility
      and 184 fertile male controls recruited at the Fertility Center and Antenatal
      Care Center, University Hospital, Malmo and Lund, Sweden. Serum folate, red cell
      folate (RCF), serum B12, plasma tHcy and semen quality were measured. Subjects
      were genotyped for 20 common variants in 12 genes related to
      folate/B12/homocysteine metabolism. Metabolite concentrations and genotype
      distributions were compared between cases and controls using linear and logistic
      regression with adjustment for covariates. The phosphatidylethanolamine N
      methyltransferase (PEMT) M175V and TCblR rs173665 polymorphisms were
      significantly associated with infertility (P=0.01 and P=0.009, respectively), but
      not with semen quality. Among non-users of supplements, infertile men had lower
      serum folate concentrations than fertile men (12.89 vs. 14.73 nmol l(-1);
      P=0.02), but there were no significant differences in RCF, B12 or tHcy. Folate,
      B12 and tHcy concentrations were not correlated with any semen parameters. This
      study provides little support for low folate or B12 status in the pathogenesis of
      idiopathic male infertility. Although additional data are needed to confirm these
      initial findings, our results suggest that PEMT and TCblR, genes involved in
      choline and B12 metabolism, merit further investigation in idiopathic male
      infertility.

PMID- 21857690
TI  - Abiraterone plus prednisone improves survival in metastatic castration-resistant
      prostate cancer.

PMID- 21857692
TI  - High-resolution digital holography utilized by the subpixel sampling method.
AB  - A novel (to our knowledge) approach for resolution improvement in digital
      holography is presented in this paper. The proposed method is based on recording
      the incoming interference field on a complementary metal-oxide semiconductor
      (CMOS) camera with subpixel resolution. The method takes advantage of the small
      pixel size of the CMOS sensor, while overcoming the reduced fill factor. This
      paper describes the experimental and numerical procedures. The improvement of the
      obtainable optical resolution, image quality, and phase measurement accuracy are
      demonstrated within this paper.

PMID- 21857693
TI  - Laser damage properties of TiO2/Al2O3 thin films grown by atomic layer
      deposition.
AB  - Research on thin film deposited by atomic layer deposition (ALD) for laser damage
      resistance is rare. In this paper, it has been used to deposit TiO(2)/Al(2)O(3)
      films at 110  degrees C and 280  degrees C on fused silica and BK7 substrates.
      Microstructure of the thin films was investigated by x-ray diffraction. The laser
      induced damage threshold (LIDT) of samples was measured by a damage test system.
      Damage morphology was studied under a Nomarski differential interference contrast
      microscope and further checked under an atomic force microscope. Multilayers
      deposited at different temperatures were compared. The results show that the
      films deposited by ALD had better uniformity and transmission; in this paper, the
      uniformity is better than 99% over 100 mm Phi samples, and the transmission is
      more than 99.8% at 1064 nm. Deposition temperature affects the deposition rate
      and the thin film microstructure and further influences the LIDT of the thin
      films. As to the TiO(2)/Al(2)O(3) films, the LIDTs were 6.73+/-0.47 J/cm(2) and
      6.5+/-0.46 J/cm(2) at 110  degrees C on fused silica and BK7 substrates,
      respectively. The LIDTs at 11  degrees C are notably better than 280  degrees C.

PMID- 21857694
TI  - Polarization and spin angular momentum in periodically rocking superlattice.
AB  - The evolution of polarization and spin angular momentum (SAM) in periodically
      rocking superlattices (PRS) is investigated. Unlike in the birefringent crystal,
      they exhibit unusual properties. The evolution of polarization shows many
      remarkable trajectories and the SAM oscillates inside the PRS. The results may
      find applications in polarization-state or optical SAM control.

PMID- 21857695
TI  - Fast identification of substance by measuring two Raman peaks with dual strip
      silicon photomultipliers and gated photon counting technique.
AB  - In this report, we use carbon tetrachloride as an example to demonstrate that
      substance can be quickly identified through the measurement of the two Raman
      peaks simply by an integrated module of dual strip silicon photomultipliers
      operating at room temperature in conjunction with a gated photon counting
      technique. Both the peak positions and the relative intensity ratio of the two
      Raman peaks are used to identify the substance with a reduced false acceptance
      rate. A complete Raman spectrum of the substance can also be measured by using
      this method combined with a scanning monochromator.

PMID- 21857696
TI  - Multiple transmitter performance with appropriate amplitude modulation for free
      space optical communication.
AB  - The propagation of a free-space optical communications signal through atmospheric
      turbulence experiences random fluctuations in intensity, including signal fades,
      which negatively impact the performance of the communications link. The gamma
      gamma probability density function is commonly used to model the scintillation of
      a single beam. One proposed method to reduce the occurrence of scintillation
      induced fades at the receiver plane involves the use of multiple beams
      propagating through independent paths, resulting in a sum of independent gamma
      gamma random variables. Recently an analytical model for the probability
      distribution of irradiance from the sum of multiple independent beams was
      developed. Because truly independent beams are practically impossible to create,
      we present here a more general but approximate model for the distribution of
      beams traveling through partially correlated paths. This model compares favorably
      with wave-optics simulations and highlights the reduced scintillation as the
      number of transmitted beams is increased. Additionally, a pulse-position
      modulation scheme is used to reduce the impact of signal fades when they occur.
      Analytical and simulated results showed significantly improved performance when
      compared to fixed threshold on/off keying.

PMID- 21857697
TI  - Spot distribution measurement using a scanning nanoslit.
AB  - A scanning and rotating nanoslit is used to measure submicrometer features in
      focused spot distributions. Using a filtered backprojection technique, a highly
      accurate reconstruction is demonstrated. Experimental results are confirmed by
      simulating the scanning slit technique using a physical optics simulation
      program. Analysis of various error mechanisms is reported, and the reconstruction
      algorithm is determined to be very resilient. The slit is 125 nm wide and 50 MUm
      long and is fabricated on a 120 nm thick layer of aluminum. The size of the image
      field is 15 MUm, and simulations indicate that 200 nm Rayleigh resolution is
      possible with an infinitely narrow slit.

PMID- 21857698
TI  - Performance assessment of onboard and scene-based methods for Airborne Prism
      Experiment spectral characterization.
AB  - Accurate spectral calibration of airborne and spaceborne imaging spectrometers is
      essential for proper preprocessing and scientific exploitation of high spectral
      resolution measurements of the land and atmosphere. A systematic performance
      assessment of onboard and scene-based methods for in-flight monitoring of
      instrument spectral calibration is presented for the first time in this paper.
      Onboard and ground imaging data were collected at several flight altitudes using
      the Airborne Prism Experiment (APEX) imaging spectrometer. APEX is equipped with
      an in-flight characterization (IFC) facility allowing the evaluation of
      radiometric, spectral, and geometric system properties, both in-flight and on
      ground for the full field of view. Atmospheric and onboard filter spectral
      features present in at-sensor radiances are compared with the same features in
      reference transmittances convolved to varying instrument spectral configurations.
      A spectrum-matching algorithm, taking advantage of the high sensitivity of
      measurements around sharp spectral features toward spectrometer spectral
      performance, is used to retrieve channel center wavelength and bandwidth
      parameters. Results showed good agreement between spectral parameters estimated
      using onboard IFC and ground imaging data. The average difference between
      estimates obtained using the O(2) and H(2)O features and those obtained using the
      corresponding filter features amounted to about 0.3 nm (0.05 of a spectral
      pixel). A deviation from the nominal laboratory instrument spectral calibration
      and an altitude-dependent performance was additionally identified. The relatively
      good agreement between estimates obtained by the two approaches in similar
      spectral windows suggests they can be used in a complementary fashion: while the
      method relying on atmospheric features can be applied without the need for
      dedicated calibration acquisitions, the IFC allows assessment at user-selectable
      wavelength positions by custom filters as well as for the system on-ground.

PMID- 21857699
TI  - Optimal proportional relation between laser power and pulse number for the
      fabrication of surface-microstructured silicon.
AB  - We experimentally demonstrate that, under the same laser fluence, there exists an
      optimal proportional relation between the laser power and pulse number for the
      fabrication of surface-microstructured silicon. During this fabrication process,
      the pulse number represents the interaction time between the laser and the
      silicon, which determines the depth of energy transferred into the inner part of
      the material, while the laser power determines the ablation and volatilization
      rate of the silicon. The proper combination of laser power and pulse number can
      ablate the material on the silicon surface effectively and have enough time to
      transfer the energy into the deep layer, which can produce microstructured
      silicon with a high spike. In addition, we compare the absorptance of samples
      etched by different combinations of laser power and pulse number; the
      corresponding results further prove the existence of an optimal proportional
      relation.

PMID- 21857700
TI  - Laser differential confocal lens refractive index measurement.
AB  - A new laser differential confocal lens refractive index measurement is proposed,
      which uses the absolute zero of the differential confocal axial intensity curve
      to precisely identify the positions of the objective when the measurement pencil
      is focused on the vertex of the test lens and the reflector with or without the
      test lens in the measurement light-path, and then uses aberration compensation
      and ray tracing facet iterative calculation to obtain the refractive index of the
      test lens, thereby achieving the high-precision noncontact measurement of lens
      refractive index. The theoretical analyses and preliminary experiments indicate
      that the accuracy of the approach can reach about 2.5*10(-4).

PMID- 21857701
TI  - Automated compensation of misalignment in phase retrieval based on a spatial
      light modulator.
AB  - In this paper, the issue of misalignment in phase retrieval by means of optical
      linear filtering is discussed. The filtering setup is based on a 4f configuration
      with a spatial light modulator (SLM) as an active element, located in the Fourier
      domain. From the analysis, crucial parameters for the alignment procedure of the
      setup's optical axes and the center of the SLM are identified. Furthermore, a
      method to automatically as well as electronically compensate such effects by
      modifying the phase pattern displayed on the SLM is introduced. Experimental
      results are presented that validate the compensation approach.

PMID- 21857702
TI  - Permanent magnets for Faraday rotators inspired by the design of the magic
      sphere.
AB  - Faraday polarization rotators are commonly used in laser experiments. Most
      Faraday materials have a nonnegligible absorption, which is a limiting factor for
      high power laser optical isolators or for intracavity optical diodes. By using a
      stronger magnetic field and a shorter length of Faraday material, one can obtain
      the same polarization rotation and a reduced absorption. In this paper, we
      describe two permanent magnet arrangements that are easy to build and produce
      magnetic fields up to 1.7 T, substantially more than commonly used. The field
      homogeneity is largely sufficient for a 30 dB isolation ratio. We finally discuss
      the prospects for producing even larger fields with permanent magnets.

PMID- 21857703
TI  - Bilayer fractal structure with multiband left-handed characteristics.
AB  - We present a bilayer fractal structure for the realization of multiband left
      handed metamaterial at terahertz frequencies. The structure is composed of
      metallic H-fractal pairs separated by a dielectric layer. The electromagnetic
      properties of periodic H-fractal pairs have been investigated by numerical
      simulation. The period in the propagation direction is extremely small as
      compared to the wavelength at the operational frequency. Under the
      electromagnetic wave normal incidence, the material exhibits negative refraction
      simultaneously around the frequencies of 0.10 and 0.15 THz for parallel
      polarization, and around the frequencies of 0.19 and 0.38 THz for perpendicular
      polarization. The design provides a left-handed metamaterial suitable for
      multiband and compact devices at terahertz frequencies.

PMID- 21857704
TI  - Improved multiple-pass Raman spectrometer.
AB  - An improved Raman gain spectrometer for flame measurements of gas temperature and
      species concentrations is described. This instrument uses a multiple-pass optical
      cell to enhance the incident light intensity in the measurement volume. The Raman
      signal is 83 times larger than from a single pass, and the Raman signal-to-noise
      ratio (SNR) in room-temperature air of 153 is an improvement over that from a
      single-pass cell by a factor of 9.3 when the cell is operated with 100 passes and
      the signal is integrated over 20 laser shots. The SNR improvement with the
      multipass cell is even higher for flame measurements at atmospheric pressure,
      because detector readout noise is more significant for single-pass measurements
      when the gas density is lower. Raman scattering is collected and dispersed in a
      spectrograph with a transmission grating and recorded with a fast gated CCD array
      detector to help eliminate flame interferences. The instrument is used to record
      spontaneous Raman spectra from N(2), CO(2), O(2), and CO in a methane-air flame.
      Curve fits of the recorded Raman spectra to detailed simulations of nitrogen
      spectra are used to determine the flame temperature from the shapes of the
      spectral signatures and from the ratio of the total intensities of the Stokes and
      anti-Stokes signals. The temperatures measured are in good agreement with
      radiation-corrected thermocouple measurements for a range of equivalence ratios.

PMID- 21857705
TI  - Local and global surface errors evaluation using Ronchi test, without both
      approximation and integration.
AB  - We have reproduced quantitatively the technique commonly used in optical shop to
      evaluate surface error from comparison between experimental and simulated
      Ronchigrams. We used this procedure to evaluate, from Ronchigrams of any number
      of fringes, the curvature radius and/or conic constant of conic surfaces. The
      error function is calculated without using integration (numerical or polynomial)
      so the corresponding problems were avoided. Furthermore, when the error function
      is described with cubic splines, then the local errors are very well reproduced,
      which is not the case with the polynomial description. We have described the
      error functions with conical surfaces or with cubic splines, and for the best
      reproduction of experimental Ronchigram we used genetic algorithms.

PMID- 21857706
TI  - Characterization of the optical properties of an infrared blocked impurity band
      detector.
AB  - Si:As blocked impurity band detectors have been partially deprocessed and
      measured by Fourier transform spectroscopy to determine their transmittance and
      reflectance at cryogenic temperatures over the wavelength range 2 MUm to 40 MUm.
      A method is presented by which the propagation constants can be extracted from an
      inversion of the transmittance and reflectance data. The effective propagation
      constants for the active layer from 2 MUm to 20 MUm were calculated as well as
      the absorption cross section of arsenic in silicon, which agrees well with
      previous results from the literature. The infrared absorptance of the full
      detector was determined, and the analytical method also provides an estimate of
      absorption in the active layer alone. Infrared absorptance of the active layer is
      compared to the quantum yield measured by photoelectric means on similar
      detectors. The optical methods outlined here, in conjunction with standard
      electronic measurements, could be used to predict the performance of such
      detectors from measurements of the blanket films from which they are to be
      fabricated.

PMID- 21857707
TI  - Analysis of broadly tunable coupled-cavity semiconductor lasers.
AB  - We report on the spectral properties for above-threshold operation of broadly
      tunable, asymmetric multiple quantum well (AMQW), coupled-cavity InGaAsP/InP
      semiconductor diode lasers. We developed a traveling wave model to understand the
      mode selection that the lasers exhibit. We find that a weak, short external
      cavity (SXC) can be used to obtain single frequency operation on each
      longitudinal mode over the ~100 nm tuning range of the uncoated AMQW coupled
      cavity lasers. We measured the spectral properties of AMQW coupled-cavity lasers
      with and without an SXC. In a synthesized optical coherent optical tomography
      application, the use of an SXC with an AMQW coupled-cavity laser reduces the
      coherence length and hence enhances the performance of the AMQW coupled-cavity
      laser for optical coherence tomography applications.

PMID- 21857708
TI  - Method for exploring the orbital angular momentum of an optical vortex beam with
      a triangular multipoint plate.
AB  - An efficient method for exploring the orbital angular momentum of an optical
      vortex beam is provided. The method, based on a triangular multipoint plate, can
      easily determine both the sign and the magnitude of the topological charge of the
      optical vortices. We demonstrate its feasibility by measuring the orbital angular
      momentum of Laguerre-Gaussian laser beams.

PMID- 21857709
TI  - Thin holographic camera with integrated reference distribution.
AB  - Off-axis digital holography typically uses a beam splitter to combine reference
      and object waves at an angle matched to the sampling period of the sensor array.
      The beam splitter determines the thickness of the recording system. This paper
      describes and demonstrates a total internal reflection hologram that replaces the
      beam splitter and enables hologram recording over a large aperture with a thin
      camera.

PMID- 21857710
TI  - Research on ultrafine particle size measurement using small amounts of data.
AB  - The paper puts forward a new method of ultrafine particle size measurement using
      small amounts of data of a dynamic light-scattering signal, and establishes an
      arithmetic model of the measurement by wavelet package transform. First, through
      the wavelet package transform, the ultrafine particle dynamic light-scattering
      signals were decomposed into multifrequency bands. Then, the noise of signals of
      different frequency bands were removed and the power spectrum of the wavelet
      packet coefficients of each frequency band was calculated. Finally, the ultrafine
      particle size distribution information could be deduced from inversing the power
      spectrum. The standard polystyrene particles of 100, 300, and 400 nm were
      measured using this method, and the inversion results indicated that this method
      can effectively remove noise and improve the accuracy of particle size
      measurement using small amounts of data.

PMID- 21857711
TI  - Compact lens with circular spot profile for square die LEDs in multi-LED
      projectors.
AB  - In the stage illumination industry, LED technology is promising both in terms of
      energy use and novel features, but it also has inherent issues. This paper
      presents a solution to the poor color homogeneity arising when multiple
      rectangular images formed from LED dies are combined into a circular spot
      profile. Using ray tracing, a nonrotationally symmetric collimating lens was
      optimized to round off such die images. The result is a high-output lens with an
      almost perfectly circular spot. In a simulated red green blue color mixing
      projector with seven LEDs, the lens reduced measurable color inhomogeneity by
      ~24.1%, with a 5.3% luminous gain, compared to the best rotationally symmetric
      benchmark lens.

PMID- 21857712
TI  - Photonic bandgaps of different unit cells in the basic structural unit of
      germanium-based two-dimensional decagonal photonic quasi-crystals.
AB  - Based on the infrared optical material germanium, in the basic structural unit of
      a two-dimensional decagonal photonic quasi-crystal, photonic bandgaps of four
      square unit cells with a scattering radius in the range of [0,0.3a] have been
      calculated within two cases of construction (i.e., air cylinders arranged in
      germanium and germanium cylinders arranged in air) by using the plane wave
      expansion method. In considering the Bragg-like scattering effect in two
      dimensional photonic quasi-crystals as the elastic collision in physics, we put
      forward the photonic bandgap impact function F=q(1)q(2)q(3)epsilonpir(2) for the
      first time, to the best of our knowledge. A certain unit cell structure shares
      some similar photonic bandgap properties with a periodic structure. For a certain
      structure of the unit cell, the center frequency change trends of the photonic
      bandgap and the type of photonic bandgap generated are not related with the
      period of the photonic crystal, but with the relative dielectric constant and the
      construction, respectively. Different unit cell structures own different photonic
      bandgap structures. This occurs because the high degree of rotational symmetry of
      the quasi-periodic structure and weak long-range order of the basic structural
      unit lead to different Bragg-like scattering effects within the unit cell
      structures.

PMID- 21857713
TI  - Measurements and simulations of polarization states of underwater light in clear
      oceanic waters.
AB  - Polarization states of the underwater light field were measured by a
      hyperspectral and multiangular polarimeter and a video polarimeter under various
      atmospheric, surface, and water conditions, as well as solar and viewing
      geometries, in clear oceanic waters near Port Aransas, Texas. Some of the first
      comprehensive comparisons were made between the measured polarized light,
      including the degree and angle of linear polarization and linear Stokes
      parameters (Q and U), and those from Monte Carlo simulations that used
      concurrently measured water inherent optical properties and particle volume
      scattering functions as input. For selected wavelengths in the visible spectrum,
      measured and model-simulated polarization characteristics were found to be
      consistent in most cases. Measured degree and angle of linear polarization are
      found to be largely determined by an in-water single-scattering model. Model
      simulations suggest that the degree of linear polarization (DoLP) at horizontal
      viewing directions is highly dependent on the viewing azimuth angle for a low
      solar elevation. This implies that animals can use the DoLP signal for
      orientation.

PMID- 21857714
TI  - Basic angles in microelectromechanical system scanning grating spectrometers.
AB  - Modern miniaturized scanning grating spectrometers (SGSs) are often based on
      microelectromechanical system devices. In contrast to classical spectrometers,
      such systems exhibit additional design constraints, like a symmetrical motion of
      the grating with a limited deflection. A detailed mathematical analysis of
      typical SGS configurations based on the grating equation considering these
      constraints is presented. Equations that relate the basic angles on a scanning
      grating to the grating properties and the attainable wavelength range of a
      spectrometer are derived, and the solution set is examined. Furthermore, the
      analytical description can be used to optimize SGSs with symmetrically moving
      gratings. The attainable spectral range for a given deflection amplitude of the
      grating can be calculated. Alternatively, the required grating properties can be
      determined for a given spectral range.

PMID- 21857715
TI  - Localized Fourier transform filter for noise removal in electronic speckle
      pattern interferometry wrapped phase patterns.
AB  - This article is concerned with frequency filtering for electronic speckle pattern
      interferometry wrapped phase patterns. We propose a robust localized Fourier
      transform filter which is an extension of the root filtering method (RFM). We
      improve the RFM from a simple technical process and a filter function in the
      frequency domain. In our method, the proposed filter function is taken as the
      power spectrum of the convolution of an image and a Gaussian function to the
      power alpha. We test the proposed method on two computer-simulated wrapped phase
      fringe patterns and one experimentally obtained wrapped phase pattern, and
      compare our models with the widely used, well-known RFM and windowed Fourier
      filtering (WFF). The experimental results have demonstrated that our localized
      Fourier transform filter outperforms the RFM and is comparable to WFF. Our method
      depends on fewer parameters, as compared with WFF, and can achieve a better
      balance between the computational complexity and the filtered results.

PMID- 21857716
TI  - Choice Inconsistencies Among the Elderly: Evidence from Plan Choice in the
      Medicare Part D Program.
AB  - We evaluate the choices of elders across their insurance options under the
      Medicare Part D Prescription Drug plan, using a unique data set of prescription
      drug claims matched to information on the characteristics of choice sets. We
      document that elders place much more weight on plan premiums than on expected out
      of pocket costs; value plan financial characteristics beyond any impacts on their
      own financial expenses or risk; and place almost no value on variance reducing
      aspects of plans. Partial equilibrium welfare analysis implies that welfare would
      have been 27% higher if patients had all chosen rationally.

PMID- 21857717
TI  - Automated auditory recognition training and testing.
AB  - Laboratory training and testing of auditory recognition skills in animals is
      important for understanding animal communication systems that depend on auditory
      cues. Songbirds are commonly studied because of their exceptional ability to
      learn complex vocalizations. In recent years, mounting interest in the perceptual
      abilities of songbirds has increased the demand for laboratory behavioural
      training and testing paradigms. Here, we describe and demonstrate the success of
      a method for auditory discrimination experiments, including all the necessary
      hardware, training procedures and freely-available, versatile software. The
      system can run several behavioural training and testing paradigms, including
      operant (go-nogo, stimulus preference, and two-alternative forced choice) and
      classical conditioning tasks. The software and some hardware components can be
      used with any laboratory animal that learns and responds to sensory cues. The
      peripheral hardware and training procedures are designed for use with songbirds
      and auditory stimuli. Using the go-nogo paradigm of the training system, we show
      that adult zebra finches learn to recognize and correctly classify individual
      female calls and male songs. We also show that learning the task generalizes to
      new stimulus classes; birds that learned the task with calls subsequently learned
      to recognize songs faster than did birds that learned the task and songs at the
      same time.

PMID- 21857718
TI  - Predicting First Grade Reading Performance from Kindergarten Response to Tier 1
      Instruction.
AB  - Many schools are beginning to implement multi-tier response to intervention (RTI)
      models for the prevention of reading difficulties and to assist in the
      identification of students with learning disabilities (LD). The present study was
      part of our larger ongoing longitudinal RTI investigation within the Florida
      Learning Disabilities Center grant. This study used a longitudinal correlational
      design, conducted in 7 ethnically and socio-economically diverse schools. We
      observed reading instruction in 20 classrooms, examined response rates to
      kindergarten Tier 1 instruction, and predicted students' first grade reading
      performance based upon kindergarten growth and end of year reading performance (n
      = 203). Teachers followed an explicit core reading program and overall, classroom
      instruction was rated as effective. Results indicate that controlling for
      students' end of kindergarten reading, their growth across kindergarten on a
      variety of language and literacy measures suppressed predictions of first grade
      performance. Specifically, the steeper the students' trajectory to a satisfactory
      outcome, the less likely they were to demonstrate good performance in first
      grade. Implications for future research and RTI implementation are discussed.

PMID- 21857719
TI  - Pharmacogenetics in Ghana.

PMID- 21857720
TI  - Review of orbital exenterations in Korle-Bu teaching hospital.
AB  - BACKGROUND: Orbital exenteration (OE) is a disfiguring procedure which typically
      involves removal of the entire contents of the orbit including the periorbita,
      appendages, eyelids and, sometimes, a varying amount of surrounding skin and
      bone. It results in devastating functional, aesthetic and psychological losses.
      DESIGN: This study reports an experience of OE in a Teaching Hospital in Accra
      Ghana. METHOD: The records of all patients who underwent OE between November 2005
      and October 2009 were reviewed retrospectively. These were cases seen at the
      orbit and oculoplastic clinic of the eye unit. RESULTS: A total of 25 patients
      underwent OE. Nineteen (76%) of these were for invasive orbital squamous cell
      carcinomas and six (24%) were for other cases. Only one patient had OE for a
      benign condition (orbital haemangioma). Four patients had lid sparing procedures.
      One of these was for a patient with extensive ocular surface squamous cell
      carcinoma. Five patients had recurrent tumours. Among those patients with
      squamous cell carcinoma, seven had previous procedures, sometimes multiple before
      reporting to our clinic. CONCLUSION: Orbital exenterations in developing
      countries are mostly for neglected periorbital and ocular surface malignancies.
      Educating patients to seek medical attention as soon as they notice a persistent
      conjunctival growth could prevent this.

PMID- 21857721
TI  - Ocular leprosy in institutionalized Nigerian patients.
AB  - OBJECTIVE: This study was aimed at presenting the profile of ocular lesions
      observed in the in-mates on multidrug treatment, of a leprosy rehabilitation
      centre in Nigeria. DESIGN: Cross-sectional. METHOD: One hundred patients were
      selected by systematic random sampling. Sixty-nine had ocular involvement and
      were the subjects of this study. The age range was 15 to 80 years with a mean age
      of 51 years. There were 57 males (82.6%) and 12 females (17.4%). The range of
      duration of treatment was two months to 30 years, with a mean of 15 years.
      Examination of the anterior and posterior segments of the globe and its adnexa
      was carried out using Penlight, magnifying loupe and direct ophthalmoscope.
      Visual acuity was recorded using the Snellen charts. RESULTS: Lepromatous leprosy
      patients had the greatest incidence of ocular lesions. Ocular lesions were more
      in patients who have had leprosy for >= 15 years. Madarosis (72.5%) and
      lagophthalmos (29.0%) were the commonest lesions. Corneal involvement was seen in
      36.2%. Conjunctivitis in 14.5% . Trichiasis in 10.1% and ectropion in 8.7% .
      17.4% were legally blind (VA<=3/60) in the better eye, and 17.4% had cataract in
      at least one eye. There was no statistically significant difference in the
      incidence of ocular lesions among males and females, and between patients with
      Lepromatous and Tuberculoid leprosy. CONCLUSION: Ocular complications are common
      and sight threatening in leprosy patients. Regular screening and outreach by eye
      care providers should be incorporated into leprosy care programmes.

PMID- 21857722
TI  - HIV-AIDS related maternal mortality in Benin City, Nigeria.
AB  - OBJECTIVE: To determine the causes and characteristics of maternal deaths in HIV
      infected women. DESIGN: A retrospective study of maternal deaths in a cohort of
      HIV-infected women. SETTING: A facility-based maternal death review using case
      records and mortality summaries. METHODS: Thirty seven maternal deaths which
      occurred in HIV-infected women were reviewed in a university teaching hospital in
      southern Nigeria over a 4-year period. Causes and circumstances surrounding each
      maternal death were identified. RESULT: One in every four maternal deaths occur
      in women with HIV infection. Majority (64.9%) of the women presented in advanced
      stage (WHO stage III/IV) of HIV syndrome while 86.5% had missed opportunities for
      antiretroviral programme. Pregnancy-related sepsis was the commonest cause of
      maternal death. Other common causes were death from tuberculosis and pneumonia.
      CONCLUSION: HIV-related maternal death is emerging as a leading cause of
      pregnancy related death in Nigeria. There is need to scale-up preconception care
      and ensure comprehensive and sustainable prevention of mother -to-child
      transmission service for all pregnant women throughout Nigeria to reduce the
      burden of HIV/AIDS infection and minimize avoidable deaths from opportunistic
      infections.

PMID- 21857723
TI  - Diabetic foot care: self reported knowledge and practice among patients attending
      three tertiary hospital in Nigeria.
AB  - BACKGROUND: Diabetes Mellitus (DM) foot complications are a leading cause of
      mortality in developing countries and the prevalence of diabetes is expected to
      increase in the next decades in these countries. The aim of this study was to
      determine the knowledge and practice of foot care among diabetes patients
      attending three tertiary hospitals in Nigeria. METHODS: This is a cross-sectional
      study carried out from November 2009 to April 2010. Pre-tested structured
      questionnaires were administered by medical officers to diabetes patients. The
      outcome variables were knowledge and practice regarding foot care. The knowledge
      and practice scores were classified as good if score >=70%, satisfactory if score
      was 50-69% and poor if score was < 50%. RESULTS: Of 352 diabetes patients, 30.1%
      had good knowledge and 10.2 % had good practice of DM foot care. Majority (78.4%)
      of patients with poor practice had poor knowledge of foot care. With regard to
      knowledge, 68.8% were unaware of the first thing to do when they found
      redness/bleeding between their toes and 61.4% were unaware of the importance of
      inspecting the inside of the footwear for objects. Poor foot practices include;
      89.2% not receiving advice when they bought footwear and 88.6% failing to get
      appropriate size footwear. Illiteracy and low socioeconomic status were
      significantly associated with poor knowledge and practice of foot care.
      CONCLUSION: This study has highlighted the gaps in the knowledge and practice of
      foot care in DM patients and underscores the need for an educational programme to
      reduce of diabetic foot complication.

PMID- 21857724
TI  - Management of contractures: a five-year experience at Komfo Anokye Teaching
      Hospital in Kumasi.
AB  - BACKGROUND: Contractures are common complications of wounds healing by secondary
      intention; some cases are idiopathic and a few are congenital. Contractures cause
      significant morbidity to patients. OBJECTIVE: The study was undertaken to
      document the pattern, spectrum and management of patients with contractures of
      various types and aetiologies presenting at a Plastic and Reconstructive Surgical
      Unit in Ghana. DESIGN: Prospective study from January 2004 to December 2008.
      SETTING: Komfo Anokye Teaching Hospital (KATH) in Kumasi PATIENTS AND METHODS:
      The age, sex, site, extent and cause of contracture was documented. The patients
      were examined and functional impairment recorded. A clinical photograph was
      taken. Patients requiring surgery had their contractures released and the defect
      repaired with an appropriate reconstructive technique. Patients with minimal
      functional impairment underwent physical therapy without surgery. RESULTS: Sixty
      eight patients comprising 44 males and 24 females were seen. Male to female ratio
      is 1.83:1. Their ages ranged from 0.66 to 60 years, mean age was 22.53 years.
      Seventy-six contractures were studied. Fifty-eight of the lesions were in the
      upper part of the body. Burns, infections and trauma were the main aetiological
      causes. Seventy-one surgical procedures were performed including release and flap
      repair (33), full thickness skin graft (23) and partial thickness skins graft and
      splinting (six). CONCLUSIONS: Thermal burns and soft tissue infections are the
      commonest causes of contractures presenting at KATH in Kumasi. These causes of
      contractures are preventable by early and adequate treatment of the acute
      conditions.

PMID- 21857726
TI  - Term abdominal pregnancy with healthy newborn: a case report.
AB  - Abdominal pregnancy is a rare form of ectopic pregnancy with very high morbidity
      and mortality for both the mother and the foetus. Diagnosis and management can
      pose some difficulties especially in low-resource centres. High index of
      suspicion is vital in making prompt diagnosis in such situations. A case of
      abdominal pregnancy that resulted in a live healthy newborn at a Regional
      Hospital in Ghana is presented.

PMID- 21857725
TI  - Pharmacogenetics in Ghana: reviewing the evidence.
AB  - Different clinical response of different patients to the same medicine has been
      recognised and documented since the 1950's. Variability in response of
      individuals to standard doses of drug therapy is important in clinical practice
      and can lead to therapeutic failures or adverse drug reactions. Pharmacogenetics
      seeks to identify individual genetic differences (polymorphisms) in drug
      absorption, metabolism, distribution and excretion that can affect the activity
      of a particular drug with the view of improving efficacy and reducing toxicity.
      Although knowledge of pharmacogenetics is being translated into clinical practice
      in the developed world, its applicability in the developing countries is low.
      Several factors account for this including the fact that there is very little
      pharmacogenetic information available in many indigenous African populations
      including Ghanaians. A number of genes including Cytochrome P450 (CYP) 2A6,
      CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, MDR1 and TPMT have been genotyped in the
      Ghanaian population since the completion of the Human genome project. There is
      however, an urgent need to increase pharmacogenetic research in Ghana to increase
      availability of data. Introducing Pharmacogenetics into the curriculum of Medical
      and Pharmacy training institutions will influence translating knowledge of
      pharmacogenetics into clinical practice. This will also equip health
      professionals with the skill to integrate genetic information into public health
      decision making.

PMID- 21857727
TI  - Cuff inflation to aid nasotracheal intubation using the C-MAC videolaryngoscope.
AB  - A preliminary report is presented of a technique for using the C-MAC
      videolaryngoscope to carry out nasopharyngeal intubations. The main thrust of the
      technique is that cuff inflation of the endotracheal tube is used to lift the
      endotracheal tube off the posterior pharyngeal wall and thus direct it towards
      the glottis. The technique was used successfully in 5 consecutive patients
      needing nasotracheal intubation. Indeed a couple of these patients might have
      been difficult to intubate using conventional laryngoscopy. The full technique is
      described together with pictures at the various stages of intubation.

PMID- 21857738
TI  - Prevalence of intimate partner violence victimization and perpetration among
      youth in Hawai'i.
AB  - OBJECTIVE: The purpose of the current study was to examine the prevalence of
      intimate partner violence (IPV) among teens in Hawai'i. METHODS: Youth from two
      O'ahu high schools (N = 623) were asked to complete a quantitative survey about
      their experiences, as victims and perpetrators, of IPV. RESULTS: The most
      frequently reported type of violence was monitoring/controlling behaviors. Girls
      reported higher rates of victimization and perpetration than boys for most
      violence types. CONCLUSIONS: Future research should examine the contexts in which
      teen IPV occurs. It will also be important to engage community-based
      organizations in prevention efforts. Therefore, a train-the-trainer curriculum
      for IPV prevention and intervention is proposed.

PMID- 21857739
TI  - Thrombophilia and ovarian hyperstimulation syndrome: a case report.
AB  - BACKGROUND: Ovarian Hyperstimulation syndrome (OHSS) is one of the most serious
      complications of controlled ovarian hyperstimulation. Recent prospective data
      revealed possible increased prevalence of thrombophilia markers in women who
      develop severe ovarian hyperstimulation syndrome (OHSS). CASE: A 26-year-old
      nulliparous woman underwent ovarian stimulation for in vitro fertilization with
      recombinant follicle stimulating hormone and developed severe OHSS. She was
      screened for hereditary and inherited thrombophilia markers and was found to be
      homozygous for MTHFR mutation and had decreased antithrombin levels. CONCLUSION:
      This case adds to the limited information that there may be an association
      between women who develop severe ovarian hyperstimulation syndrome and an
      increased prevalence of underlying thrombophilia markers. If further research
      demonstrates a cost effective strategy, screening for those markers may identify
      women who are at a higher risk for development of severe ovarian hyperstimulation
      syndrome.

PMID- 21857740
TI  - Idiopathic granulomatous mastitis associated with corynebacterium sp. Infection.
AB  - Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the
      breast. The etiology and treatments options of IGM remain controversial. Previous
      case reports have suggested that Corynebacterium sp., a gram-positive bacillus
      endogenous to the skin, may be associated with IGM. In the present report, we
      describe the first case of IGM with a positive culture for Corynebacterium sp.
      reported in the United States.

PMID- 21857741
TI  - For our children: the National Children's Study.

PMID- 21857743
TI  - Phthalocyaninato complexes with peripheral alkylthio chains: disk-like adsorbate
      species for the vertical anchoring of ligands on gold surfaces.
AB  - Thin metalorganic films were prepared on gold by self-assembly of thioether
      functionalised phthalocyaninato complexes from solution. The phthalocyaninato
      ligands used contain eight peripheral, beta-positioned, alkylthio substituents SR
      (1a: R = n-C(8)H(17), 1b: R = n-C(12)H(25)), which serve as headgroups for
      surface binding and promote lateral assembly, while the disk-like
      phthalocyaninato core offers the scope for the attachment of axial ligands to the
      adsorbed molecules. This process was mimicked by coordination of pyridine (Py) to
      [Zn(1a)] and [Zn(1b)], respectively. The crystal structures of the products
      [Zn(1a)(Py)] and [Zn(1b)(Py)] were determined. The crystal structures of 4,5
      bis(octylthio)phthalodinitrile and 4,5-bis(dodecylthio)phthalodinitrile were also
      determined. The films fabricated from [Mn(1a)Cl] and [Mn(1b)Cl] on gold were
      characterised by XPS, ToF-SIMS and NEXAFS spectroscopy, which revealed the
      presence of well-defined and homogeneous self-assembled monolayers (SAMs), whose
      constituents are bound to the substrate by thioether-gold linkages. The
      orientation of the macrocycles is predominantly parallel to the surface. Strong
      electronic interaction of the manganese(III) centre with the substrate leads to
      Cl loss upon adsorption and its reduction to Mn(II).

PMID- 21857744
TI  - Confined compression of dental composites for Class I restorations.
AB  - This study focuses on the mechanical response of a particle-reinforced
      restorative dental composite (RenewTM) under proportional transverse confinement
      to understand the effects of stress multiaxiality on its mechanical and failure
      behaviors. We describe the confining ring technique as an experimental tool to
      introduce multiaxial compressive stress states in dental composites that
      realistically mimic three-dimensional stress states commonly experienced by
      dental restorations in the oral cavity. Effect of initial radial misfit between
      confining ring and specimen is analyzed through computational finite element
      simulations, and an analytical treatment of problem is also provided to compute
      the confining stress during elasto-plastic expansion of confining ring.
      Experimental results suggest that inelastic response of Renew composite is
      significantly influenced by hydrostatic stress component, and pressure-dependent
      yield functions are required to analyze plastic deformations and internal damage
      accumulation process.

PMID- 21857745
TI  - A Sharp-Interface Immersed Boundary Method with Improved Mass Conservation and
      Reduced Spurious Pressure Oscillations.
AB  - A method for reducing the spurious pressure oscillations observed when simulating
      moving boundary flow problems with sharp-interface immersed boundary methods
      (IBMs) is proposed. By first identifying the primary cause of these oscillations
      to be the violation of the geometric conservation law near the immersed boundary,
      we adopt a cut-cell based approach to strictly enforce geometric conservation. In
      order to limit the complexity associated with the cut-cell method, the cut-cell
      based discretization is limited only to the pressure Poisson and velocity
      correction equations in the fractional-step method and the small-cell problem
      tackled by introducing a virtual cell-merging technique. The method is shown to
      retain all the desirable properties of the original finite-difference based IBM
      while at the same time, reducing pressure oscillations for moving boundaries by
      roughly an order of magnitude.

PMID- 21857747
TI  - Wh-questions: Moving beyond the first Phase.
AB  - The paper presents a feature-checking theory of wh-movement that attempts to
      accommodate both adult grammar and the path of acquisition by which children
      handle long distance movement, indirect questions and partial movement. Partial
      movement is not a grammatical option in English but it is adopted as an option in
      development. The account makes several predictions about the performance of
      children with Specific Language impairment (SLI), and also predicts a particular
      advantage for children who speak African American English (AAE) over those who
      speak Mainstream American English (MAE). The empirical data are taken from a
      study of 590 children, both typically-developing and language-impaired, and both
      AAE and MAE speaking, aged four to nine years. The tasks involved answering wh
      questions after stories as part of the field-testing of a new language assessment
      instrument. The questions included multi-clause questions with or without medial
      wh-complementizers. The predictions are borne out that children with language
      impairment have prolonged difficulty with real long distance movement and medial
      questions, and that children who speak AAE are at an advantage in avoiding
      certain errors (partial movement) because of the dialect's characteristic marking
      of indirect questions via inversion in the lower clause.

PMID- 21857746
TI  - Statistical Mechanics of Nucleosomes Constrained by Higher-Order Chromatin
      Structure.
AB  - Eukaryotic DNA is packaged into chromatin: one-dimensional arrays of nucleosomes
      separated by stretches of linker DNA are folded into 30-nm chromatin fibers which
      in turn form higher-order structures (Felsenfeld and Groudine in Nature 421:448,
      2003). Each nucleosome, the fundamental unit of chromatin, has 147 base pairs
      (bp) of DNA wrapped around a histone octamer (Richmond and Davey in Nature
      423:145, 2003). In order to describe how chromatin fiber formation affects
      nucleosome positioning and energetics, we have developed a thermodynamic model of
      finite-size particles with effective nearest-neighbor interactions and arbitrary
      DNA-binding energies. We show that both one-and two-body interactions can be
      extracted from one-particle density profiles based on high-throughput maps of in
      vitro or in vivo nucleosome positions. Although a simpler approach that neglects
      two-body interactions (even if they are in fact present in the system) can be
      used to predict sequence determinants of nucleosome positions, the full theory is
      required to disentangle one- and two-body effects. Finally, we construct a
      minimal model in which nucleosomes are positioned primarily by steric exclusion
      and two-body interactions rather than intrinsic histone-DNA sequence preferences.
      The model reproduces nucleosome occupancy patterns observed over transcribed
      regions in living cells.

PMID- 21857748
TI  - Bayesian gene set analysis for identifying significant biological pathways.
AB  - We propose a hierarchical Bayesian model for analyzing gene expression data to
      identify pathways differentiating between two biological states (e.g., cancer vs.
      non-cancer and mutant vs. normal). Finding significant pathways can improve our
      understanding of biological processes. When the biological process of interest is
      related to a specific disease, eliciting a better understanding of the underlying
      pathways can lead to designing a more effective treatment. We apply our method to
      data obtained by interrogating the mutational status of p53 in 50 cancer cell
      lines (33 mutated and 17 normal). We identify several significant pathways with
      strong biological connections. We show that our approach provides a natural
      framework for incorporating prior biological information, and it has the best
      overall performance in terms of correctly identifying significant pathways
      compared to several alternative methods.

PMID- 21857749
TI  - Properties of preliminary test estimators and shrinkage estimators for evaluating
      multiple exposures - Application to questionnaire data from the SONIC study.
AB  - Epidemiology studies increasingly examine multiple exposures in relation to
      disease by selecting the exposures of interest in a thematic manner. For example,
      sun exposure, sunburn, and sun protection behavior could be themes for an
      investigation of sun-related exposures. Several studies now use pre-defined
      linear combinations of the exposures pertaining to the themes to estimate the
      effects of the individual exposures. Such analyses may improve the precision of
      the exposure effects, but they can lead to inflated bias and type I errors when
      the linear combinations are inaccurate. We investigate preliminary test
      estimators and empirical Bayes type shrinkage estimators as alternative
      approaches when it is desirable to exploit the thematic choice of exposures, but
      the accuracy of the pre-defined linear combinations is unknown. We show that the
      two types of estimator are intimately related under certain assumptions. The
      shrinkage estimator derived under the assumption of an exchangeable prior
      distribution gives precise estimates and is robust to misspecifications of the
      user-defined linear combinations. The precision gains and robustness of the
      shrinkage estimation approach are illustrated using data from the SONIC study,
      where the exposures are the individual questionnaire items and the outcome is
      (log) total back nevus count.

PMID- 21857750
TI  - Labor Market Outcomes for Legal Mexican Immigrants Under the New Regime of
      Immigration Enforcement.
AB  - OBJECTIVES: This paper documents the effects of increasingly restrictive
      immigration and border policies on Mexican migrant workers in the United States. 
      METHODS: Drawing on data from the Mexican Migration Project we create a data file
      that links age, education, English language ability, and cumulative U.S.
      experience in three legal categories (documented, undocumented, guest worker) to
      the occupational status and wage attained by migrant household heads on their
      most recent U.S. trip.  RESULTS: We find that the wage and occupational returns
      to various forms of human capital generally declined after harsher policies were
      imposed and enforcement dramatically increased after 1996, especially for U.S.
      experience and English language ability.  CONCLUSION: These results indicate that
      the labor market status of legal immigrants has deteriorated significantly in
      recent years as larger shares of the migrant workforce came to lack labor rights,
      either because they were undocumented or because they held temporary visas that
      did not allow mobility or bargaining over wages and working conditions.

PMID- 21857751
TI  - Asymmetric Nazarov Cyclizations.

PMID- 21857752
TI  - Development of a Double Allylboration Reagent Targeting 1,5-syn-(E)-Diols:
      Application to the Synthesis of the C(23)-C(40) Fragment of Tetrafibricin.
AB  - Interest in the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin prompted
      us to develop a new method for the synthesis of 1,5-syn-(E)-diols. Toward this
      end, the kinetically controlled hydroboration of allenes 6, 33, ent-39, 42 and 45
      with the Soderquist borane 25R were studied. Tetrabutylammonium
      allenyltrifluoroborate 45 gave superior results and was utilized in a double
      allylboration sequence with two different aldehydes to provide the targeted 1,5
      syn-(E)-diols in generally high yields (72-98%), and with high enantioselectivity
      (>95% e.e.), diastereoselectivity (d.r. >20:1), and (E)/(Z) selectivity (>20:1).
      This new method was applied to the synthesis of the C(23)-C(40) fragment 2 of
      tetrafibricin.

PMID- 21857753
TI  - Isolation and Characterization of Actinoramides A-C, Highly Modified Peptides
      from a Marine Streptomyces sp.
AB  - Reported herein is the isolation and structure elucidation of three highly
      modified peptides, actinoramides A-C (1-3), which are produced by a marine
      bacterium closely related to the genus Streptomyces. The planar structures of the
      actinoramides, which are composed of the unusual amino acids 2-amino-4
      ureidobutanoic acid and 4-amino-3-hydroxy-2-methyl-5-phenylpentanoic acid, were
      assigned by chemical transformations and by interpretation of spectroscopic data,
      while the absolute configuration of these new peptides were defined by
      application of the advanced Marfey's and Mosher's methods.

PMID- 21857754
TI  - Toward a total synthesis of the stemofoline alkaloids: Advancement of a 1,3
      dipolar cycloaddition strategy.
AB  - Novel, intramolecular 1,3-dipolar cycloadditions of azomethine ylides have been
      applied to the synthesis of functionalized core structures of the stemofoline
      alkaloids. In an effort to maximize the efficiency of this key transformation in
      the context of an eventual total synthesis of these complex natural products, a
      number of strategic modifications to the cycloaddition substrate were
      investigated. These collective efforts have provided useful insights into the
      operative, regiochemical control elements for 1,3-dipolar cycloadditions leading
      to stemofoline alkaloids. A potential intermediate in the synthesis of these
      alkaloids was prepared.

PMID- 21857755
TI  - Preparation of phenalenes and hydronaphthacenes through tandem alkyne Fischer
      carbene complex coupling and inter- or intramolecular Diels-Alder reactions.
AB  - The rapid construction of phenalenes through the reaction of 8-alkynyltetralones
      with Fischer carbine complexes followed by either inter- or an intramolecular
      Diels-Alder reaction is presented. As a showcase of the synthetic utility of this
      process, the rapid construction of polycyclic ring systems containing the
      tetracycline core has been demonstrated through an iterative application of this
      reaction sequence.

PMID- 21857756
TI  - Azomethine ylide mediated inversion of configuration of quaternary imidazoline
      carbon: converting trans- to its cis- imidazolines.
AB  - An efficient synthetic methodology of converting trans-4,5-diaryl-2-imidazolines
      to the corresponding cis-4,5-diaryl-2-imidazolines has been developed. This
      methodology features mild reaction conditions and a simple one-pot two-step
      procedure.

PMID- 21857757
TI  - Intramolecular Cyclization Strategies Toward the Synthesis of Zoanthamine
      Alkaloids.
AB  - Stabilized 2-amino-1,3-dienes can participate in intramolecular Diels-Alder
      (IMDA) reactions with pendant dienophiles. We found that these dienes can be
      readily prepared via standard palladium-mediated coupling reactions and have
      comparable reactivity to 2-oxodienes. Application of these substrates to the
      synthesis of tetracyclic model systems representing the ABCE motif of the
      zoanthamines is presented.

PMID- 21857758
TI  - The Impact of Research Grant Funding on Scientific Productivity.
AB  - In this paper, we estimate the impact of receiving an NIH grant on subsequent
      publications and citations. Our sample consists of all applications (unsuccessful
      as well as successful) to the NIH from 1980 to 2000 for standard research grants
      (R01s). Both OLS and IV estimates show that receipt of an NIH research grant
      (worth roughly $1.7 million) leads to only one additional publication over the
      next five years, which corresponds to a 7 percent increase. The limited impact of
      NIH grants is consistent with a model in which the market for research funding is
      competitive, so that the loss of an NIH grant simply causes researchers to shift
      to another source of funding.

PMID- 21857760
TI  - Complete set of material properties of [011](c) poled 0.24Pb(In(1/2)Nb(1/2))O(3)
      0.46Pb(Mg(1/3)Nb(2/3))O(3)-0.30PbTiO(3) single crystal.
AB  - A complete set of elastic, piezoelectric, and dielectric constants of [011](c)
      poled multidomain 0.24Pb(In(1/2)Nb(1/2))O(3)-0.46Pb(Mg(1/3)Nb(2/3))O(3)
      0.30PbTiO(3) ternary single crystal has been determined using resonance and
      ultrasonic methods and the temperature dependence of the dielectric permittivity
      has been measured at 3 different frequencies. The experimental results revealed
      that this [011](c) poled ternary single crystal has very large transverse
      piezoelectric coefficient d(32) = -1693 pC/N, transverse dielectric constant
      epsilon(11)/epsilon(0) ~ 7400 and a high electromechanical coupling factor k(32)
      ~ 90%. In addition, its coercive field is 2 times of that of the corresponding
      binary 0.7Pb(Mg(1/3)Nb(2/3))O(3)-0.30PbTiO(3) single system with much better
      temperature stability. Therefore, the crystal is an excellent candidate for
      transverse mode electromechanical devices.

PMID- 21857759
TI  - A longitudinal examination of risky sexual behaviors among Canadian and Italian
      adolescents: Considering individual, parental, and friend characteristics.
AB  - In this study, two longitudinal models of early adolescent risky sexual behaviors
      (RSB) were compared using a pooled sample of 267 Canadian and Italian adolescents
      (55% females; 53% Canadians) assessed yearly from grade 8 to 10. We focused on
      parenting practices (monitoring, control, limit setting), adolescent problem
      behaviors (antisocial behaviors, substance use) and their friends' deviance
      (antisocial behaviors, substance use) as predictors of condom use frequency and
      lifetime number of sexual partners. The socialization model postulates that
      youths' problem behaviors and RSB are behaviors learned within the friendship
      network where deviancy training can occur. The selection model posits that
      delinquent youth tend to affiliate with each other, and that RSB is one of many
      behaviors that can form the basis of selection. Using structural equation
      modeling, this study showed that the socialization model was the most accurate to
      explain the emergence of RSB. A full mediation of parenting practices, passing
      through deviant friends and youths' problem behavior, was observed for condom
      use. The same process applied to number of sexual partners, but a direct effect
      for parenting practices was also found.

PMID- 21857761
TI  - Who's the Boss? Patterns of Control in Adolescents' Sibling Relationships.
AB  - The goals of this study were to examine longitudinal changes in perceived control
      in adolescents' sibling relationships and to describe the nature and correlates
      of three distinct control patterns: Firstborn dominant, equal, and secondborn
      dominant. Firstborn and secondborn adolescents in 184 predominately European
      American families participated in home interviews and a series of phone
      interviews as part of a longitudinal a study of family relationships and
      adolescent development. Findings revealed changes in control over three years as
      well as sibling differences. In addition, different patterns of control were
      linked to qualities of the sibling relationship and to adolescent adjustment. The
      different roles that firstborn and secondborn siblings assume, and why these
      roles are linked to relationship experiences and adjustment, are discussed.

PMID- 21857762
TI  - Comparison of Optimal Design Methods in Inverse Problems.
AB  - Typical optimal design methods for inverse or parameter estimation problems are
      designed to choose optimal sampling distributions through minimization of a
      specific cost function related to the resulting error in parameter estimates. It
      is hoped that the inverse problem will produce parameter estimates with increased
      accuracy using data collected according to the optimal sampling distribution.
      Here we formulate the classical optimal design problem in the context of general
      optimization problems over distributions of sampling times. We present a new
      Prohorov metric based theoretical framework that permits one to treat succinctly
      and rigorously any optimal design criteria based on the Fisher Information Matrix
      (FIM). A fundamental approximation theory is also included in this framework. A
      new optimal design, SE-optimal design (standard error optimal design), is then
      introduced in the context of this framework. We compare this new design criteria
      with the more traditional D-optimal and E-optimal designs. The optimal sampling
      distributions from each design are used to compute and compare standard errors;
      the standard errors for parameters are computed using asymptotic theory or
      bootstrapping and the optimal mesh. We use three examples to illustrate ideas:
      the Verhulst-Pearl logistic population model [13], the standard harmonic
      oscillator model [13] and a popular glucose regulation model [16, 19, 29].

PMID- 21857765
TI  - Gender Wage Inequality and Economic Growth: Is There Really a Puzzle?-A Comment.
AB  - Seguino (2000) shows that gender wage discrimination in export-oriented semi
      industrialized countries might be fostering investment and growth in general.
      While the original analysis does not have internationally comparable wage
      discrimination data, we replicate the analysis using data from a meta-study on
      gender wage discrimination and do not find any evidence that more discrimination
      might further economic growth-on the contrary: if anything the impact of gender
      inequality is negative for growth. Standing up for more gender equality-also in
      terms of wages-is good for equity considerations and at least not negative for
      growth.

PMID- 21857763
TI  - Interpersonal Goals and Susceptibility to Peer Influence: Risk Factors for
      Intentions to Initiate Substance Use during Early Adolescence.
AB  - Though peer socialization theories are prominent in the adolescent substance use
      literature, variability in the degree to which adolescents are vulnerable to peer
      influence is likely, and few studies have examined this issue. This study
      examines the association between perceived peer substance use/approval of
      substance use and adolescent intentions to initiate alcohol and cigarette use,
      and how social goals moderate this relationship. Results support the moderating
      role of social goals, and suggest important differences across alcohol and
      cigarette use. Peer use and approval of cigarette use was associated with future
      intentions to smoke for adolescents with strong agentic goals, and peer use and
      approval of alcohol use was associated with intentions to drink for adolescents
      with strong communal goals. These findings suggest that adolescent substance use
      theories and prevention programs focusing on peer socialization should consider
      individual differences in social goals and potential differences in peer
      influence across drugs.

PMID- 21857766
TI  - Molecular Phylogenetic and Morphological Evidence Supports Recognition of
      Gereaua, a New Endemic Genus of Sapindaceae from Madagascar.
AB  - A recent worldwide phylogeny of Sapindaceae inferred from nuclear and plastid DNA
      regions segregated the Malagasy Haplocoelum perrieri Capuron from the African
      Haplocoelum foliosum (Hiern) Bullock. Additional phylogenetic analyses conducted
      here (including material of Haplocoelum inopleum Radlk., the generic type)
      supported the result from the previous analysis and showed that maintaining a
      broad circumscription of Haplocoelum to include the Malagasy species would render
      the genus polyphyletic. To maintain monophyly, it is necessary to exclude H.
      perrieri, which we transfer to a new, monotypic genus, described here as Gereaua.
      This taxon is easily distinguished from the species retained in Haplocoelum by
      the following morphological characters: (1) sexually dimorphic inflorescences in
      racemules (vs. monomorphic inflorescences in fascicule of cymes); (2) 2-locular
      ovary (vs. 3-locular ovary); (3) rudimentary pistillode in staminate flowers (vs.
      no pistillode in staminate flowers); (4) corolla with 4 or 5 petals (vs.
      apetalous); (5) pubescent fruit (vs. glabrous fruit). Relationships between the
      new genus and its most closely related genera, included in the Macphersonia
      group, are discussed in light of molecular, morphological and biogeographic
      evidence. A preliminary threat assessment of Gereaua perrieri using the IUCN Red
      List criteria indicates a status of Least Concern.

PMID- 21857767
TI  - New species from the Galoka and Kalabenono massifs: two unknown and severely
      threatened mountainous areas in NW Madagascar.
AB  - The Galoka mountain chain, comprising principally the Galoka and Kalabenono
      massifs, situated at the northern edge of the Sambirano Region in NW Madagascar
      is an area that was virtually unknown botanically. It was visited three times
      between 2005 and 2007 as part of a floristic inventory. Both massifs contain the
      last remaining primary forests in the Galoka chain, which extends parallel to the
      coastline from South of Ambilobe to North of Ambanja. Several new species have
      been discovered amongst the collections, eight of which are described here.

PMID- 21857769
TI  - Anxiety, Substance Use, and Their Co-Occurrence: Advances in Clinical Science.
AB  - Research and clinical literatures are replete with examples that psychological
      disorders are related to drug use, abuse, and dependence. The preponderance of
      scientific work addressing relations among psychopathological processes and drug
      use, abuse, and dependence has been focused primarily on psychotic disorders,
      major depression, antisocial personality disorder, and attention deficit
      hyperactivity disorder. This corpus of empirical work has indicated that there
      are clinically meaningful relations among particular types of psychopathology and
      the onset and maintenance of substance use behaviors and disorders and, in turn,
      that substance use and use-related problems can impact vulnerability for
      psychopathology. Within this public health context, it is striking that despite
      the fact that anxiety disorders are one of the most common classes of
      psychological problems (Kessler et al., 2005), there has been limited
      programmatic study of the relations between anxiety vulnerability processes and
      substance use disorders.

PMID- 21857768
TI  - Teriparatide Therapy as an Adjuvant for Tissue Engineering and Integration of
      Biomaterials.
AB  - Critically sized large bone defects commonly result from trauma, radical tumor
      resections or infections. Currently, massive allografting remain as the clinical
      standard to treat these critical defects. Unfortunately, allograft healing is
      limited by the lack of osteogenesis and bio-integration of the graft to the host
      bone. Based on its widely studied anabolic effects on the bone, we have proposed
      that teriparatide [recombinant parathyroid hormone (PTH(1-34))] could be an
      effective adjuvant for massive allograft healing. In support of this theory, here
      we review studies that have demonstrated that intermittent PTH(1-34) treatment
      enhances and accelerates the skeletal repair process via a number of mechanisms
      including: effects on mesenchymal stem cells (MSC), angiogenesis, chondrogenesis,
      bone formation and remodeling. We also review the current literature on the
      effects of PTH(1-34) therapy on bone healing, and discuss this drug's long term
      potential as an adjuvant for endogenous tissue engineering.

PMID- 21857770
TI  - Pets, depression and long term survival in community living patients following
      myocardial infarction.
AB  - Evidence supports the contribution of depression, anxiety, and poor social
      support to mortality of hospitalized myocardial infarction (MI) patients. The
      contribution of depression to survival is independent of disease severity. Pet
      ownership, a non-human form of social support, has also been associated with one
      year survival of post-MI patients. The current study addresses whether pet
      ownership contributes independently to long term survival beyond the
      contributions of depression, anxiety, or low social support in post-MI patients
      who have already survived at least 6 months. Data from patients (N = 460)
      enrolled in the "Psychosocial Responses in the Home Automated External
      Defibrillator Trial (PR-HAT)"were used. Seventeen patients died during a median
      follow-up of 2.8 years. In Cox proportional hazards regression model that
      included depression, lack of pet ownership, and the interaction between
      depression and lack of pet ownership, not owning a pet was the only significant
      independent predictor of mortality (p = 0.036). The interaction between pet
      ownership and depression tended to be significant indicating that the effect of
      pet ownership on survival in this group of people who have supportive
      spouses/companions living with them may relate to depression.

PMID- 21857771
TI  - Lumpen Abuse: The Human Cost of Righteous Neoliberalism.
AB  - I thank the Society for Urban Anthropology for the Anthony Leeds Book Prize. The
      award gives me special pleasure because I think of myself primarily as an urban
      anthropologist. I was trained in "peasant studies" as a student of Eric Wolf's in
      the late 1970s and early 1980s eager to conduct participant-observation fieldwork
      on the revolutionary movements taking place in Central America in those decades.
      It was a hopeful - even inspiring - moment in history at my doctoral fieldwork
      theme/sites: the agrarian reform in the Amerindian Moskitia territory of
      Sandinista Nicaragua (1979-80, 1984), guerrilla warfare in an FMLN-controlled
      territory in El Salvador (1981), and farmworker organizing on a United Fruit
      Company plantation enclave spanning the Costa Rica/Panama Caribbean border (1982
      1984). During these exciting years of fieldwork, however, I found myself longing
      to return to my hometown to conduct ethnography on the same themes that I was
      witnessing in the countryside of Central America: the political
      mobilization/demobilization of class struggle in the context of racialized
      ethnicity and extreme social inequality. Consequently, while writing up my
      dissertation (Bourgois 1989), I moved to East Harlem two dozen blocks from where
      I had grown up in New York City to document what I came to call "US inner-city
      apartheid." That was in March of 1985 and ever since, my work has been primarily
      dedicated to understanding urban social inequality.

PMID- 21857772
TI  - Photopatterned materials in bioanalytical microfluidic technology.
AB  - Microfluidic technologies are playing an increasingly important role in
      biological inquiry. Sophisticated approaches to the microanalysis of biological
      specimens rely, in part, on the fine fluid and material control offered by
      microtechnology, as well as a sufficient capacity for systems integration. A
      suite of techniques that utilize photopatterning of polymers on fluidic surfaces,
      within fluidic volumes, and as primary device structures underpins recent
      technological innovation in bioanalysis. Well-characterized photopatterning
      approaches enable previously fabricated or commercially fabricated devices to be
      customized by the user in a straight-forward manner, making the tools accessible
      to laboratories that do not focus on microfabrication technology innovation. In
      this review of recent advances, we summarize reported microfluidic devices with
      photopatterned structures and regions as platforms for a diverse set of
      biological measurements and assays.

PMID- 21857773
TI  - Integrated strain array for cellular mechanobiology studies.
AB  - We have developed an integrated strain array for cell culture enabling high
      throughput mechano-transduction studies. Biocompatible cell culture chambers were
      integrated with an acrylic pneumatic compartment and microprocessor-based control
      system. Each element of the array consists of a deformable membrane supported by
      a cylindrical pillar within a well. For user-prescribed waveforms, the annular
      region of the deformable membrane is pulled into the well around the pillar under
      vacuum, causing the pillar-supported region with cultured cells to be stretched
      biaxially. The optically clear device and pillar-based mechanism of operation
      enables imaging on standard laboratory microscopes. Straightforward fabrication
      utilizes off-the-shelf components, soft lithography techniques in
      polydimethylsiloxane, and laser ablation of acrylic sheets. Proof of
      compatibility with basic biological assays and standard imaging equipment were
      accomplished by straining C2C12 skeletal myoblast cells on the device for 6
      hours. At higher strains, cells and actin stress fibers realign with a
      circumferential preference.

PMID- 21857775
TI  - Characterizing and Optimizing Rater Performance for Internet-based Collaborative
      Labeling.
AB  - Labeling structures on medical images is crucial in determining clinically
      relevant correlations with morphometric and volumetric features. For the
      exploration of new structures and new imaging modalities, validated automated
      methods do not yet exist, and so researchers must rely on manually drawn
      landmarks. Voxel-by-voxel labeling can be extremely resource intensive, so large
      scale studies are problematic. Recently, statistical approaches and software have
      been proposed to enable Internet-based collaborative labeling of medical images.
      While numerous labeling software tools have been created, the use of these
      packages as high-throughput labeling systems has yet to become entirely viable
      given training requirements. Herein, we explore two modifications to a typical
      mouse-based labeling system: (1) a platform independent overlay for recognition
      of mouse gestures and (2) an inexpensive touch-screen tracking device for non
      mouse input. Through this study we characterize rater reliability in point, line,
      curve, and region placement. For the mouse input, we find a placement accuracy of
      2.48+/-5.29 pixels (point), 0.630+/-1.81 pixels (curve), 1.234+/-6.99 pixels
      (line), and 0.058+/-0.027 (1 - Jaccard Index for region). The gesture software
      increased labeling speed by 27% overall and accuracy by approximately 30-50% on
      point and line tracing tasks, but the touch screen module lead to slower and more
      error prone labeling on all tasks, likely due to relatively poor sensitivity. In
      summary, the mouse gesture integration layer runs as a seamless operating system
      overlay and could potentially benefit any labeling software; yet, the inexpensive
      touch screen system requires improved usability optimization and calibration
      before it can provide an efficient labeling system.

PMID- 21857774
TI  - Exotic Fruits as Therapeutic Complements for Diabetes, Obesity and Metabolic
      Syndrome.
AB  - The prevalence and severity of obesity, type 2-diabetes, and the resultant
      metabolic syndrome are rapidly increasing. As successful preventive and
      therapeutic strategies for these life-threatening health ailments often come with
      adverse side effects, nutritional elements are widely used in many countries as
      preventive therapies to prevent or manage metabolic syndrome. Fruits are
      important dietary components, and contain various bioactive constituents. Many of
      these constituents have been proven to be useful to manage and treat various
      chronic diseases such as diabetes, obesity, cancer and cardiovascular diseases.
      Although exotic fruits are understudied throughout the world due to their limited
      regional presence, many studies reveal their potent ability to ameliorate
      metabolic derangements and the resultant conditions i.e. diabetes and obesity.
      The aim of this article is to review the role of exotic fruits and their
      constituents in the regulation of metabolic functions, which can beneficially
      alter diabetes and obesity pathophysiology.

PMID- 21857776
TI  - Accentuation of Individual Differences in Social Competence During the Transition
      to Adolescence.
AB  - Using a sample of individuals (277 males, 315 females) studied since birth in the
      NICHD Study of Early Child Care and Youth Development, the present study
      investigated how early pubertal maturation and school transition alter youth
      trajectories of social competence during the transition to adolescence. Social
      competence showed strong continuity, with the most socially competent children
      remaining so in adolescence. Early pubertal maturation and school transitions
      accentuate individual differences, increasing social competence among more
      competent youth, but further diminishing social competence among less competent
      individuals. In essence, facing challenges that require social competence may
      further separate competent individuals from less competent peers. Thus, the
      psychosocially rich become richer, while the psychosocially poor become poorer.

PMID- 21857777
TI  - Taking learning to the learner: using audio teleconferencing for postclinical
      conferences and more.
AB  - Clinical educators are often burdened by conflicts that occur as they try to
      balance multiple postclinical scheduling demands with students' varying
      timetables. The purpose of this article is to inform educators how to use
      teleconferences to deliver valuable postclinical debriefing, model professional
      growth experiences, and more. The innovative use of teleconferencing as a
      pedagogical method enables educators to take learning to the learners.

PMID- 21857778
TI  - Role of Robotics in Neurorehabilitation.
AB  - Over the past decade, rehabilitation hospitals have begun to incorporate robotics
      technologies into the daily treatment schedule of many patients. These
      interventions hold greater promise than simply replicating traditional therapy,
      because they allow therapists an unprecedented ability to specify and monitor
      movement features such as speed, direction, amplitude, and joint coordination
      patterns and to introduce controlled perturbations into therapy. We argue that to
      fully realize the potential of robotic devices in neurorehabilitation, it is
      necessary to better understand the specific aspects of movement that should be
      facilitated in rehabilitation. In this article, we first discuss neurorecovery in
      the context of motor control and learning principles that can provide guidelines
      to rehabilitation professionals for enhancing recovery of motor function. We then
      discuss how robotic devices can be used to support such activities.

PMID- 21857779
TI  - Dose-response curve to salbutamol during acute and chronic treatment with
      formoterol in COPD.
AB  - BACKGROUND: Use of short-acting beta(2)-agonists in chronic obstructive pulmonary
      disease (COPD) during treatment with long-acting beta(2)-agonists is recommended
      as needed, but its effectiveness is unclear. The purpose of this study was to
      assess the additional bronchodilating effect of increasing doses of salbutamol
      during acute and chronic treatment with formoterol in patients with COPD.
      METHODS: Ten patients with COPD underwent a dose-response curve to salbutamol
      (until 800 MUg of cumulative dose) after a 1-week washout (baseline), 8 hours
      after the first administration of formoterol 12 MUg (day 1), and after a 12-week
      and 24-week period of treatment with formoterol (12 MUg twice daily by dry powder
      inhaler). Peak expiratory flow, forced expiratory volume in one second (FEV(1)),
      forced vital capacity, and inspiratory capacity were measured at the different
      periods of treatment and at different steps of the dose-response curve. RESULTS:
      Despite acute or chronic administration of formoterol, maximal values of peak
      expiratory flow, FEV(1), and forced vital capacity after 800 MUg of salbutamol
      were unchanged compared with baseline. The baseline FEV(1) dose-response curve
      was steeper than that at day 1, week 12, or week 24 (P < 0.0001). Within each
      dose-response curve, FEV(1) was different only at baseline and at day 1 (P <
      0.001), when FEV(1) was still greater at 800 MUg than at 0 MUg (P < 0.02). In
      contrast, the forced vital capacity dose-response curves were similar at the
      different periods, while within each dose-response curve, forced vital capacity
      was different in all instances (P < 0.001), always being higher at 800 MUg than
      at 0 MUg (P < 0.05). CONCLUSION: In patients with stable COPD, the maximal effect
      of salbutamol on peak expiratory flow, FEV(1), and forced vital capacity was
      unchanged after either acute or chronic treatment with formoterol. With
      increasing doses of salbutamol, FEV(1) increased only after acute administration
      of formoterol. Forced vital capacity also significantly improved during long-term
      treatment with formoterol.

PMID- 21857780
TI  - Monitoring and analysis of lung sounds remotely.
AB  - Visual and auditory analysis of respiratory sound signals promises improved
      detection of certain types of lung diseases. LabVIEW software was used to design
      a system that monitors the respiratory activity of the patient. The program
      developed calculates the respiratory rate, displays the time expanded waveform of
      the lung sound, and computes the fast Fourier transform and short-time Fourier
      transform to present the power spectrum and spectrogram respectively. These
      parameters are transmitted synchronously to the remote station using the Internet
      for online monitoring of the patient.

PMID- 21857781
TI  - Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and
      inflammation.
AB  - Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant
      features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype
      of airflow obstruction. COPD pulmonary physiology reflects the sum of
      pathological changes in COPD, which can occur in large central airways, small
      peripheral airways, and the lung parenchyma. Quantitative or high-resolution
      computed tomography is used as a surrogate measure for assessment of disease
      progression. Different biological or molecular markers have been reported that
      reflect the mechanistic or pathogenic triad of inflammation, proteases, and
      oxidants and correspond to the different aspects of COPD histopathology. Similar
      to the pathogenic triad markers, genetic variations or polymorphisms have also
      been linked to COPD-associated inflammation, protease-antiprotease imbalance, and
      oxidative stress. Furthermore, in recent years, there have been reports
      identifying aging-associated mechanistic markers as downstream consequences of
      the pathogenic triad in the lungs from COPD patients. For this review, the
      authors have limited their discussion to a review of mechanistic markers and
      genetic variations and their association with COPD histopathology and disease
      status.

PMID- 21857783
TI  - Stress disorder and PTSD after burn injuries: a prospective study of predictors
      of PTSD at Sina Burn Center, Iran.
AB  - BACKGROUND: A burn injury can be a traumatic experience with tremendous social,
      physical, and psychological consequences. The aim of this study was to
      investigate the existence of post-traumatic stress disorder (PTSD) and predictors
      of PTSD Checklist score initially and 3 months after injury in burns victims
      admitted to the Sina Burn Center in north-west Iran. METHODS: This prospective
      study examined adult patients aged 16-65 years with unintentional burns. The PTSD
      Checklist was used to screen for PTSD. RESULTS: Flame burns constituted 49.4% of
      all burns. Mean PTSD score was 23.8 +/- 14.7 early in the hospitalization period
      and increased to 24.2 +/- 14.3, 3 months after the burn injury. Twenty percent of
      victims 2 weeks into treatment had a positive PTSD screening test, and this
      figure increased to 31.5% after 3 months. The likelihood of developing a positive
      PTSD screening test increased significantly after 3 months (P < 0.01). Using
      multivariate regression analysis, factors independently predicting PTSD score
      were found to be age, gender, and percentage of total body surface area burned.
      CONCLUSION: PTSD was a problem in the population studied and should be managed
      appropriately after hospital admission due to burn injury. Male gender, younger
      age, and higher total body surface area burned may predict a higher PTSD score
      after burn injury.

PMID- 21857782
TI  - Excessive visceral fat accumulation in advanced chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Previous studies have suggested links between chronic obstructive
      pulmonary disease (COPD), cardiovascular disease, and abdominal obesity. Although
      abdominal visceral fat is thought to be associated with cardiovascular risk
      factors, the degree of visceral fat accumulation in patients with COPD has not
      been directly studied. The aim of this study was to investigate the abdominal
      visceral fat accumulation and the association between visceral fat and the
      severity and changes in emphysema in COPD patients. METHODS: We performed
      clinical and laboratory tests, including pulmonary function, dyspnea score, and
      the six-minute walking test in COPD patients (n = 101) and control, which
      included subjects with a smoking history but without airflow obstruction (n =
      62). We used computed tomography to evaluate the abdominal visceral fat area
      (VFA), subcutaneous fat area (SFA), and the extent of emphysema. RESULTS: The
      COPD group had a larger VFA than the control group. The prevalence of non-obese
      subjects with an increased VFA was greater in the Global Initiative for Chronic
      Obstructive Lung Disease Stages III and IV than in the other stages of COPD. The
      extent of emphysema was inversely correlated with waist circumference and SFA.
      However, VFA did not decrease with the severity of emphysema. VFA was positively
      correlated with the degree of dyspnea. CONCLUSION: COPD patients have excessive
      visceral fat, which is retained in patients with more advanced stages of COPD or
      severe emphysema despite the absence of obesity.

PMID- 21857784
TI  - Ginkgo biloba extract in the treatment of tinnitus: a systematic review.
AB  - Tinnitus is a symptom frequently encountered by ear, nose, and throat
      practitioners. A causal treatment is rarely possible, and drug and nondrug
      treatment options are limited. One of the frequently prescribed treatments is
      Ginkgo biloba extract. Therefore, randomized, placebo-controlled clinical trials
      of Ginkgo biloba extract preparations were searched for and reviewed
      systematically. There is evidence of efficacy for the standardized extract, EGb
      761((r)) (Dr Willmar Schwabe GmbH & Co KG Pharmaceuticals, Karlsruhe, Germany),
      in the treatment of tinnitus from three trials in patients in whom tinnitus was
      the primary complaint. Supportive evidence comes from a further five trials in
      patients with age-associated cognitive impairment or dementia in whom tinnitus
      was present as a concomitant symptom. As yet, the efficacy of other ginkgo
      preparations has not been proven, which does not necessarily indicate
      ineffectiveness, but may be due to flawed clinical trials. In conclusion, EGb
      761((r)), a standardized Ginkgo biloba extract, is an evidence-based treatment
      option in tinnitus.

PMID- 21857785
TI  - Radioelectric brain stimulation in the treatment of generalized anxiety disorder
      with comorbid major depression in a psychiatric hospital: a pilot study.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is often presented with major
      depression (MD). GAD-MD can be a chronic and disabling condition, and patients
      suffering from this disorder often respond poorly to psychopharmacological
      treatment and experience side effects with medication. Therefore, there is a high
      demand for effective nonpharmacological therapy for GAD-MD patients. The current
      study explores the use of a radioelectric asymmetric conveyer (REAC) device in
      the treatment of GAD-MD. METHODS: Participants were 24 patients diagnosed with
      GAD-MD being treated at a public psychiatric center. All patients were
      dissatisfied with their current pharmacological treatment. Patients were
      evaluated using the 21-item Hamilton Depression (HAM-D) rating scale and the
      Symptom Check List-90-Revised (SCL-90R) before and after REAC brain stimulation
      treatment cycles. RESULTS: After REAC brain stimulation treatment, all patients
      experienced a significant reduction in anxiety and depression. These results were
      confirmed by physician examination, HAM-D scores, and SCL-90R total scores.
      CONCLUSION: These results indicate a role for REAC brain stimulation in the
      management of psychiatric conditions, specifically, GAD-MD comorbidity. REAC
      treatments are synergistic to drug therapy and appear to be helpful in reducing
      the side effects of medication. Future studies should evaluate the long-term
      effects of REAC treatment.

PMID- 21857786
TI  - APRESS: apical regulatory super system, serotonin, and dopamine interaction.
AB  - BACKGROUND: THE MONOAMINES SEROTONIN AND DOPAMINE ARE KNOWN TO EXIST IN TWO
      SEPARATE STATES: the endogenous state and the competitive inhibition state. The
      presence of the competitive inhibition state has been known to science for many
      years, but from a functional standpoint it has been noted in the literature as
      being "meaningless." METHODS: A large database of monoamine transporter response
      to amino acid precursor administration variations with clinical outcomes was
      accumulated. In the process, a new organic cation transporter (OCT) model has
      been published, and OCT functional status determination along with amino acid
      precursor manipulation methods have been invented and refined. RESULTS:
      Methodology was developed whereby manipulation of the OCT, in the competitive
      inhibition state, is carried out in a predictable manner. This, in turn, has
      disproved the long-held assertion that the monoamine competitive inhibition state
      is functionally meaningless. CONCLUSION: The most significant aspect of this
      paper is the documentation of newly recognized relationships between serotonin
      and dopamine. When transport of serotonin and dopamine are both in the
      competitive inhibition state, manipulation of the concentrations of one will lead
      to predictable changes in concentrations of the other. From a functional
      standpoint, processes regulated and controlled by changes to only serotonin can
      now be controlled by changes to dopamine, and vice versa, in a predictable
      manner.

PMID- 21857788
TI  - Management of acute rhinosinusitis in Danish general practice: a survey.
AB  - PURPOSE: To evaluate whether the ongoing debate over diagnostic problems and
      treatment choices for acute rhinosinusitis has had any influence on the
      management of the disease. METHODS: We randomly selected 300 Danish general
      practitioners (GPs) from the files of the Research Unit for General Practice at
      Aarhus University. Invitations to participate and a questionnaire were sent to
      the GPs by mail. RESULTS: A total of 149 (49%) GPs answered the questionnaire.
      When asked about symptoms, the highest priority was given to sinus pain and signs
      of tenderness. The most frequent examinations were objective examination of the
      ear-nose-throat (ENT), palpation of the maxillofacial area, and C-reactive
      protein point-of-care testing (or CRP rapid test). Nearly all GPs prescribed
      local vasoconstrictors, and in 70% of cases, antibiotics were prescribed.
      Phenoxymethyl-penicillin was the preferred antibiotic. Use of the CRP rapid test,
      years in practice, or employment in an ENT department did not have a significant
      impact on the diagnostic certainty and antibiotic prescribing rate. CONCLUSION:
      The clinical diagnoses are based on a few symptoms, signs, and the CRP rapid
      test. Other examinations, including imaging techniques, are seldom used.
      Phenoxymethylpenicillin is the preferred antibiotic, and the GPs' diagnostic
      certainty was 70%.

PMID- 21857789
TI  - Head and neck cancer in HIV patients and their parents: a Danish cohort study.
AB  - BACKGROUND: The mechanism for the increased risk of head and neck cancer (HNC)
      observed in HIV patients is controversial. We hypothesized that family-related
      risk factors increase the risk of HNC why we estimated the risk of this type of
      cancer in both HIV patients and their parents. METHODS: We estimated the
      cumulative incidence and incidence rate ratios (IRRs) of HNC in 1) a population
      of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5053)
      and a cohort of population controls matched on age and gender (n = 50,530) (study
      period; 1995-2009) and 2) the parents of HIV patients and population controls
      (study period 1978-2009). To assess the possible impact of human papilloma virus
      (HPV)-associated cancers, the sites of squamous cell HNCs were categorized as HPV
      related, potentially HPV related, and potentially HPV unrelated. RESULTS:
      Seventeen (0.3%) HIV patients vs 80 (0.2%) population controls were diagnosed
      with HNC cancer in the observation period. HIV patients had an increased risk of
      HNC (IRR 3.05 [95% CI 1.81-5.15]). The IRR was considerably increased in HIV
      patients older than 50 years (adjusted IRR; 4.58 [95% CI 2.24-9.35]), diagnosed
      after 1995 (adjusted IRR 6.31 [95% CI 2.82-14.08]), previous or current smoker
      (adjusted IRR 4.51 [95% CI 2.47-8.23]), with baseline CD4 count 350 cells/MUL
      (adjusted IRR; 3.89 [95% CI 1.95-7.78]), and men heterosexually infected with HIV
      (adjusted IRR 5.54 [95% CI 1.96-15.66]). Fifteen (83%) of the HIV patients
      diagnosed with HNC were current or former smokers. The IRR of squamous cell HNC
      in HIV patients was high at HPV-relate sites, potentially HPV-related sites, and
      potentially HPV-unrelated sites. Both fathers and mothers of HIV patients had an
      increased risk of HNC (adjusted IRR for fathers 1.78 [95% CI 1.28-2.48], adjusted
      IRR for mothers 2.07 [95% CI 1.05-4.09]). CONCLUSION: HIV appears to be a marker
      of behavioral or family-related risk factors that affect the incidence of HNC in
      HIV patients.

PMID- 21857787
TI  - Moderate alcohol consumption and cognitive risk.
AB  - We reviewed 143 papers that described the relationship between moderate drinking
      of alcohol and some aspect of cognition. Two types of papers were found: (1)
      those that provided ratios of risk between drinkers and nondrinkers (74 papers in
      total) and (2) those that, although they did not provide such ratios, allowed
      cognition in drinkers to be rated as "better," "no different," or "worse" than
      cognition in nondrinkers (69 papers in total). The history of research on
      moderate drinking and cognition can be divided into two eras: 1977-1997 and 1998
      present. Phase I (1977-1997) was the era of neuropsychological evaluation
      involving mostly young to middle-aged (18-50 years old) subjects. Although
      initial studies indicated moderate drinking impaired cognition, many later
      studies failed to confirm this, instead finding no difference in cognition
      between drinkers and nondrinkers. Phase II (1998-present) was and is the era of
      mental status exam evaluation involving mostly older (>=55 years old) subjects.
      These studies overwhelmingly found that moderate drinking either reduced or had
      no effect on the risk of dementia or cognitive impairment. When all the ratios of
      risk from all the studies in phase II providing such ratios are entered into a
      comprehensive meta-analysis, the average ratio of risk for cognitive risk
      (dementia or cognitive impairment/decline) associated with moderate "social" (not
      alcoholic) drinking of alcohol is 0.77, with nondrinkers as the reference group.
      The benefit of moderate drinking applied to all forms of dementia (dementia
      unspecified, Alzheimer's disease, and vascular dementia) and to cognitive
      impairment (low test scores), but no significant benefit against cognitive
      decline (rate of decline in test scores) was found. Both light and moderate
      drinking provided a similar benefit, but heavy drinking was associated with
      nonsignificantly higher cognitive risk for dementia and cognitive impairment.
      Although the meta-analysis also indicated that wine was better than beer or
      spirits, this was based on a relatively small number of studies because most
      studies did not distinguish among these different types of alcohol. Furthermore,
      a number of the studies that did make the distinction reported no difference
      among the effects of these different types of alcohol. Therefore, at present this
      question remains unanswered. Analysis also showed that the presence of the
      apolipoprotein E epsilon 4 allele eliminated the benefit of moderate drinking.
      However, this was based on a relatively small number of studies and several other
      studies have found a beneficial effect of the epsilon e4 allele. Further studies
      are necessary to settle this question. The benefit of moderate alcohol for
      cognition was seen in both men and women, although the amount and pattern of
      drinking is very different between the two sexes. Lastly, the finding of
      unaffected or significantly reduced cognitive risk in light to moderate drinkers
      was seen in 14/19 countries for which country-specific ratio data were available,
      with three of the five remaining countries showing nonsignificant reductions as
      well. Overall, light to moderate drinking does not appear to impair cognition in
      younger subjects and actually seems to reduce the risk of dementia and cognitive
      decline in older subjects.

PMID- 21857790
TI  - Physical activity and mortality among Norwegian women - the Norwegian Women and
      Cancer Study.
AB  - BACKGROUND: Physical activity (PA) and its relationship with all-cause mortality
      suggest a strong and consistent inverse association. This study prospectively
      investigated the association between PA level and mortality among participants of
      the Norwegian Women and Cancer (NOWAC) Study. METHODS: A total of 66,136 NOWAC
      participants were followed-up until December 31st 2008. PA level and possible
      confounding factors were obtained through a self-administered questionnaire at
      enrolment. Cox proportional hazards regression was used to calculate adjusted
      relative risks (RRs) and 95% confidence intervals (CIs) for all-cause,
      cardiovascular disease (CVD) and cancer mortality and PA levels defined from 1 to
      10 on a global scale. RESULTS: PA levels 1-4 were associated with a significantly
      increased risk of all-cause mortality (level 1 RR = 2.35; 95% CI: 1.94-2.84,
      level 2 RR = 1.71; 95% CI: 1.45-2.00, level 3 RR = 1.30; 95% CI: 1.14-1.49, level
      4 RR = 1.07; 95% CI: 0.95-1.22), compared with PA level 5. CVD mortality risk
      increased in PA levels 1-3 (level 1 RR = 3.50; 95% CI: 2.41-5.10, level 2 RR =
      1.50; 95% CI: 0.99-2.25, level 3 RR = 1.12; 95% CI: 0.79-1.60) as did cancer
      mortality risk (RR = 1.32; 95% CI: 0.96-1.81, RR = 1.48; 95% CI: 1.19-1.84, RR =
      1.26; 95% CI: 1.06-1.50, respectively). The magnitude of the associations was
      consistent across strata of age, smoking, and body mass index. The population
      attributable fractions for PA levels 1-4 were: all-cause mortality, 11.5%; CVD
      mortality, 11.3%; cancer mortality, 7.8%. CONCLUSION: There is a significant
      trend of increased risk of all-cause, CVD and cancer mortality in relation to low
      PA levels among Norwegian women.

PMID- 21857791
TI  - Chemistry and material science at the cell surface.
AB  - Cell surfaces are fertile ground for chemists and material scientists to
      manipulate or augment cell functions and phenotypes. This not only helps to
      answer basic biology questions but also has diagnostic and therapeutic
      applications. In this review, we summarize the most recent advances in the
      engineering of the cell surface. In particular, we focus on the potential
      applications of surface engineered cells for 1) targeting cells to desirable
      sites in cell therapy, 2) programming assembly of cells for tissue engineering,
      3) bioimaging and sensing, and ultimately 4) manipulating cell biology.

PMID- 21857792
TI  - Mass Spectrometric Analysis of Mycothiol levels in Wild-Type and Mycothiol
      Disulfide Reductase Mutant Mycobacterium smegmatis.
AB  - Mycothiol (MSH), the primary low-molecular weight thiol produced in mycobacteria,
      acts to protect the cell from oxidative stress and to maintain redox homeostasis,
      notably in the pathogenic Mycobacterium tuberculosis in the course of human
      infection. The mycothiol disulfide reductase (Mtr) enzyme reduces the oxidized
      form of mycothiol, mycothione (MSSM), back to MSH, however its role in bacterial
      viability is not clear. In this study, we sought to determine the MSH levels of
      wild-type (WT) and Mtr mutant mycobacteria during oxidative stress. We describe a
      rapid method for the relative quantification of MSH using high-sensitivity mass
      spectrometry (MS) with selected ion monitoring (SIM). This method uses only
      minimal sample cleanup, and does not require advanced chromatographic equipment
      or fluorescent compounds. MSH levels decreased in the Mtr mutant only upon
      treatment with peroxide, and the results were consistent between our method and
      previously-described thiol quantification methods. Our results indicate that our
      MS-based method is a useful, high-throughput alternative tool for the
      quantification of MSH from mycobacteria.

PMID- 21857793
TI  - Evaluation of a randomized intervention to delay sexual initiation among fifth
      graders followed through the sixth grade.
AB  - US adolescents initiate sex at increasingly younger ages, yet few pregnancy
      prevention interventions for children as young as 10-12 years old have been
      evaluated. Sixteen Washington, DC schools were randomly assigned to intervention
      versus control conditions. Beginning in 2001/02 with fifth-grade students and
      continuing during the sixth grade, students completed pre-intervention and post
      intervention surveys each school year. Each year, the intervention included 10-13
      classroom sessions related to delaying sexual initiation. Linear hierarchical
      models compared outcome changes between intervention and control groups by gender
      over time. Results show the intervention significantly decreased a rise over time
      in the anticipation of having sex in the next 12 months among intervention boys
      versus control boys, but it had no other outcome effects. Among girls, the
      intervention had no significant outcome effects. One exception is that for both
      genders, compared with control students, intervention students increased their
      pubertal knowledge. In conclusion, a school-based curriculum to delay sexual
      involvement among fifth-grade and sixth-grade high-risk youths had limited
      impact. Additional research is necessary to outline effective interventions, and
      more intensive, comprehensive interventions may be required to counteract adverse
      circumstances in students' lives and pervasive influences toward early
      sex.ClinicalTrials. gov identifier: NCT00341471.

PMID- 21857794
TI  - Parents' views on sexual debut among pre-teen children in Washington, DC.
AB  - OBJECTIVE: Present US parents' perceptions about factors leading to early
      intercourse and strategies for overcoming them.  METHODS: Conducted analysis of
      eight focus groups with 78 male and female African-American and Hispanic
      caregivers of fifth-graders and sixth-graders (ages 10-12).  RESULTS:
      Participants gave the following primary reasons for early sexual activity: lack
      of structured activities, adult supervision, and communication; and influence of
      peers, society, and media. They suggested strategies targeting these reasons, and
      the need for parents, schools, and the community to work together.  CONCLUSION:
      Incorporating parents' perspectives would help tailor interventions to the needs
      of the target population and increase parental support.

PMID- 21857795
TI  - Recognizing the Risks of Chronic Nonsteroidal Anti-Inflammatory Drug Use in Older
      Adults.
AB  - Older adults commonly take nonsteroidal anti-inflammatory drugs (NSAIDs)
      chronically. Studies of older adults show that chronic NSAID use increases the
      risk of peptic ulcer disease, acute renal failure, and stroke/myocardial
      infarction. Moreover, chronic NSAID use can exacerbate a number of chronic
      diseases including heart failure and hypertension, and can interact with a number
      of drugs (eg, warfarin, corticosteroids). Preferred analgesics in older adults
      that may have a lower risk of these adverse drug reactions include acetaminophen,
      a nonacetylated salicylate (eg, salsalate), a short half-life NSAID (eg,
      ibuprofen), or low-dose opioid/opioid-like agents in combination with
      acetaminophen (in appropriate patients).

PMID- 21857796
TI  - The Association Between Infants' Attention Control and Social Inhibition is
      Moderated by Genetic and Environmental Risk for Anxiety.
AB  - Infant social inhibition is associated with increased risk for anxiety later in
      life. Although both genetic and environmental factors are associated with
      anxiety, little empirical work has addressed how developing regulatory abilities
      work with genetic and environmental risk to exacerbate or mitigate problem
      behaviors. The current study was aimed at addressing this gap in research by
      investigating an early-emerging regulatory behavior, attention control, in
      association with genetic and environmental risk for anxiety.Participants included
      9-month-old adopted infants, their birth mothers, and adoptive parents (n = 361).
      Lifetime diagnosis of birth mother social phobia was obtained using structured
      interviews. Adoptive parents completed self-report measures of anxiety symptoms.
      Infant social inhibition and attention control were coded during a stranger
      interaction and a barrier task, respectively. Neither adoptive nor birth parent
      anxiety were directly associated with social inhibition. The association of
      attention control with social inhibition in infants was moderated by birth and
      adoptive parent anxiety symptoms. When infants of birth mothers with social
      phobia were raised by adoptive parents with high self-reported anxiety symptoms,
      greater attention control was associated with greater social inhibition. However,
      when raised by adoptive parents with low self-reported anxiety, greater attention
      control was associated with less social inhibition.

PMID- 21857797
TI  - Inorganic-Organic Nanocomposite Assembly Using Collagen as Template and Sodium
      Tripolyphosphate as A Biomimetic Analog of Matrix Phosphoprotein.
AB  - Nanocomposites created with polycarboxylic acid alone as a stabilization agent
      for prenucleation clusters-derived amorphous calcium phosphate exhibit non
      periodic apatite deposition. In the present study, we report the use of inorganic
      polyphosphate as a biomimetic analog of matrix phosphoprotein for directing
      polyacrylic acid-stabilized amorphous nanoprecursor phases to assemble into
      periodic apatite-collagen nanocomposites. The sorption and desorption
      characteristics of sodium tripolyphosphate to type I collagen was examined.
      Periodic nanocomposite assembly with collagen as a template was demonstrated with
      TEM and SEM using a Portland cement-based resin composite and a phosphate
      containing simulated body fluid. Apatite was detected within the collagen at 24
      hours and became more distinct at 48 hours, with prenucleation clusters attaching
      to the collagen fibril surface during the initial infiltration stage. Apatite
      collagen nanocomposites at 72 hours were heavily mineralized with periodically
      arranged intrafibrillar apatite platelets. Defect-containing nanocomposites
      caused by desorption of TPP from collagen fibrils were observed in regions
      lacking the inorganic phase.

PMID- 21857798
TI  - The PICU perspective on monitoring hemodynamics and oxygen transport.
AB  - Alterations of hemodynamics and oxygen transport balance are very common
      scenarios in the pediatric intensive care unit (PICU), and these alterations are
      as heterogeneous and diverse in nature as are the patient populations that
      typically exist in the PICU. Accordingly, the PICU perspective on monitoring of
      hemodynamics and oxygen transport balance in critically ill children must be
      understood in this context of heterogeneity and diversity. We provide an
      interpretation of the evidence supporting various monitoring strategies as
      presented in the The Pediatric Cardiac Intensive Care Society Evidence Based
      Review and Consensus Statement on Monitoring of Hemodynamics and Oxygen Transport
      Balance from a Pediatric Intensive Care perspective.

PMID- 21857799
TI  - Estimation of Sparse Binary Pairwise Markov Networks using Pseudo-likelihoods.
AB  - We consider the problems of estimating the parameters as well as the structure of
      binary-valued Markov networks. For maximizing the penalized log-likelihood, we
      implement an approximate procedure based on the pseudo-likelihood of Besag (1975)
      and generalize it to a fast exact algorithm. The exact algorithm starts with the
      pseudo-likelihood solution and then adjusts the pseudo-likelihood criterion so
      that each additional iterations moves it closer to the exact solution. Our
      results show that this procedure is faster than the competing exact method
      proposed by Lee, Ganapathi, and Koller (2006a). However, we also find that the
      approximate pseudo-likelihood as well as the approaches of Wainwright et al.
      (2006), when implemented using the coordinate descent procedure of Friedman,
      Hastie, and Tibshirani (2008b), are much faster than the exact methods, and only
      slightly less accurate.

PMID- 21857800
TI  - Opposing activities of LIT-1/NLK and DAF-6/patched-related direct sensory
      compartment morphogenesis in C. elegans.
AB  - Glial cells surround neuronal endings to create enclosed compartments required
      for neuronal function. This architecture is seen at excitatory synapses and at
      sensory neuron receptive endings. Despite the prevalence and importance of these
      compartments, how they form is not known. We used the main sensory organ of C.
      elegans, the amphid, to investigate this issue. daf-6/Patched-related is a glia
      expressed gene previously implicated in amphid sensory compartment morphogenesis.
      By comparing time series of electron-microscopy (EM) reconstructions of wild-type
      and daf-6 mutant embryos, we show that daf-6 acts to restrict compartment size.
      From a genetic screen, we found that mutations in the gene lit-1/Nemo-like kinase
      (NLK) suppress daf-6. EM and genetic studies demonstrate that lit-1 acts within
      glia, in counterbalance to daf-6, to promote sensory compartment expansion.
      Although LIT-1 has been shown to regulate Wnt signaling, our genetic studies
      demonstrate a novel, Wnt-independent role for LIT-1 in sensory compartment size
      control. The LIT-1 activator MOM-4/TAK1 is also important for compartment
      morphogenesis and both proteins line the glial sensory compartment. LIT-1
      compartment localization is important for its function and requires neuronal
      signals. Furthermore, the conserved LIT-1 C-terminus is necessary and sufficient
      for this localization. Two-hybrid and co-immunoprecipitation studies demonstrate
      that the LIT-1 C-terminus binds both actin and the Wiskott-Aldrich syndrome
      protein (WASP), an actin regulator. We use fluorescence light microscopy and
      fluorescence EM methodology to show that actin is highly enriched around the
      amphid sensory compartment. Finally, our genetic studies demonstrate that WASP is
      important for compartment expansion and functions in the same pathway as LIT-1.
      The studies presented here uncover a novel, Wnt-independent role for the
      conserved Nemo-like kinase LIT-1 in controlling cell morphogenesis in conjunction
      with the actin cytoskeleton. Our results suggest that the opposing daf-6 and lit
      1 glial pathways act together to control sensory compartment size.

PMID- 21857802
TI  - Sticking together helps cells capture more food and keep it from the cheaters.

PMID- 21857801
TI  - Sucrose utilization in budding yeast as a model for the origin of
      undifferentiated multicellularity.
AB  - We use the budding yeast, Saccharomyces cerevisiae, to investigate one model for
      the initial emergence of multicellularity: the formation of multicellular
      aggregates as a result of incomplete cell separation. We combine simulations with
      experiments to show how the use of secreted public goods favors the formation of
      multicellular aggregates. Yeast cells can cooperate by secreting invertase, an
      enzyme that digests sucrose into monosaccharides, and many wild isolates are
      multicellular because cell walls remain attached to each other after the cells
      divide. We manipulate invertase secretion and cell attachment, and show that
      multicellular clumps have two advantages over single cells: they grow under
      conditions where single cells cannot and they compete better against cheaters,
      cells that do not make invertase. We propose that the prior use of public goods
      led to selection for the incomplete cell separation that first produced
      multicellularity.

PMID- 21857803
TI  - Fertilizing nature: a tragedy of excess in the commons.
AB  - Globally, we are applying excessive nitrogen (N) fertilizers to our agricultural
      crops, which ultimately causes nitrogen pollution to our ecosphere. The
      atmosphere is polluted by N2O and NO(x) gases that directly and indirectly
      increase atmospheric warming and climate change. Nitrogen is also leached from
      agricultural lands as the water-soluble form NO3-, which increases nutrient
      overload in rivers, lakes, and oceans, causing "dead zones", reducing property
      values and the diversity of aquatic life, and damaging our drinking water and
      aquatic-associated industries such as fishing and tourism. Why do some countries
      show reductions in fertilizer use while others show increasing use? What N
      fertilizer application reductions could occur, without compromising crop yields?
      And what are the economic and environmental benefits of using directed nutrient
      management strategies?

PMID- 21857804
TI  - Combining genome-wide association mapping and transcriptional networks to
      identify novel genes controlling glucosinolates in Arabidopsis thaliana.
AB  - BACKGROUND: Genome-wide association (GWA) is gaining popularity as a means to
      study the architecture of complex quantitative traits, partially due to the
      improvement of high-throughput low-cost genotyping and phenotyping technologies.
      Glucosinolate (GSL) secondary metabolites within Arabidopsis spp. can serve as a
      model system to understand the genomic architecture of adaptive quantitative
      traits. GSL are key anti-herbivory defenses that impart adaptive advantages
      within field trials. While little is known about how variation in the external or
      internal environment of an organism may influence the efficiency of GWA, GSL
      variation is known to be highly dependent upon the external stresses and
      developmental processes of the plant lending it to be an excellent model for
      studying conditional GWA. METHODOLOGY/PRINCIPAL FINDINGS: To understand how
      development and environment can influence GWA, we conducted a study using 96
      Arabidopsis thaliana accessions, >40 GSL phenotypes across three conditions (one
      developmental comparison and one environmental comparison) and ~230,000 SNPs.
      Developmental stage had dramatic effects on the outcome of GWA, with each stage
      identifying different loci associated with GSL traits. Further, while the
      molecular bases of numerous quantitative trait loci (QTL) controlling GSL traits
      have been identified, there is currently no estimate of how many additional genes
      may control natural variation in these traits. We developed a novel co-expression
      network approach to prioritize the thousands of GWA candidates and successfully
      validated a large number of these genes as influencing GSL accumulation within A.
      thaliana using single gene isogenic lines. CONCLUSIONS/SIGNIFICANCE: Together,
      these results suggest that complex traits imparting environmentally contingent
      adaptive advantages are likely influenced by up to thousands of loci that are
      sensitive to fluctuations in the environment or developmental state of the
      organism. Additionally, while GWA is highly conditional upon genetics, the use of
      additional genomic information can rapidly identify causal loci en masse.

PMID- 21857805
TI  - Sex chromosome-specific regulation in the Drosophila male germline but little
      evidence for chromosomal dosage compensation or meiotic inactivation.
AB  - The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in
      females) has repeatedly elicited the evolution of two kinds of chromosome
      specific regulation: dosage compensation--the equalization of X chromosome gene
      expression in males and females--and meiotic sex chromosome inactivation (MSCI)-
      the transcriptional silencing and heterochromatinization of the X during meiosis
      in the male (or Z in the female) germline. How the X chromosome is regulated in
      the Drosophila melanogaster male germline is unclear. Here we report three new
      findings concerning gene expression from the X in Drosophila testes. First, X
      chromosome-wide dosage compensation appears to be absent from most of the
      Drosophila male germline. Second, microarray analysis provides no evidence for X
      chromosome-specific inactivation during meiosis. Third, we confirm the previous
      discovery that the expression of transgene reporters driven by autosomal
      spermatogenesis-specific promoters is strongly reduced when inserted on the X
      chromosome versus the autosomes; but we show that this chromosomal difference in
      expression is established in premeiotic cells and persists in meiotic cells. The
      magnitude of the X-autosome difference in transgene expression cannot be
      explained by the absence of dosage compensation, suggesting that a previously
      unrecognized mechanism limits expression from the X during spermatogenesis in
      Drosophila. These findings help to resolve several previously conflicting reports
      and have implications for patterns of genome evolution and speciation in
      Drosophila.

PMID- 21857807
TI  - Being the ghost in the machine: a medical ghostwriter's personal view.

PMID- 21857806
TI  - Commercial serological tests for the diagnosis of active pulmonary and
      extrapulmonary tuberculosis: an updated systematic review and meta-analysis.
AB  - BACKGROUND: Serological (antibody detection) tests for tuberculosis (TB) are
      widely used in developing countries. As part of a World Health Organization
      policy process, we performed an updated systematic review to assess the
      diagnostic accuracy of commercial serological tests for pulmonary and
      extrapulmonary TB with a focus on the relevance of these tests in low- and middle
      income countries. METHODS AND FINDINGS: We used methods recommended by the
      Cochrane Collaboration and GRADE approach for rating quality of evidence. In a
      previous review, we searched multiple databases for papers published from 1
      January 1990 to 30 May 2006, and in this update, we add additional papers
      published from that period until 29 June 2010. We prespecified subgroups to
      address heterogeneity and summarized test performance using bivariate random
      effects meta-analysis. For pulmonary TB, we included 67 studies (48% from low-
      and middle-income countries) with 5,147 participants. For all tests, estimates
      were variable for sensitivity (0% to 100%) and specificity (31% to 100%). For
      anda-TB IgG, the only test with enough studies for meta-analysis, pooled
      sensitivity was 76% (95% CI 63%-87%) in smear-positive (seven studies) and 59%
      (95% CI 10%-96%) in smear-negative (four studies) patients; pooled specificities
      were 92% (95% CI 74%-98%) and 91% (95% CI 79%-96%), respectively. Compared with
      ELISA (pooled sensitivity 60% [95% CI 6%-65%]; pooled specificity 98% [95% CI 96%
      99%]), immunochromatographic tests yielded lower pooled sensitivity (53%, 95% CI
      42%-64%) and comparable pooled specificity (98%, 95% CI 94%-99%). For
      extrapulmonary TB, we included 25 studies (40% from low- and middle-income
      countries) with 1,809 participants. For all tests, estimates were variable for
      sensitivity (0% to 100%) and specificity (59% to 100%). Overall, quality of
      evidence was graded very low for studies of pulmonary and extrapulmonary TB.
      CONCLUSIONS: Despite expansion of the literature since 2006, commercial
      serological tests continue to produce inconsistent and imprecise estimates of
      sensitivity and specificity. Quality of evidence remains very low. These data
      informed a recently published World Health Organization policy statement against
      serological tests. Please see later in the article for the Editors' Summary.

PMID- 21857808
TI  - How industry uses the ICMJE guidelines to manipulate authorship--and how they
      should be revised.

PMID- 21857809
TI  - Building the field of health policy and systems research: framing the questions.

PMID- 21857810
TI  - Serological testing versus other strategies for diagnosis of active tuberculosis
      in India: a cost-effectiveness analysis.
AB  - BACKGROUND: Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in
      India. Serological (antibody detection) TB tests are not recommended by any
      agency, but widely used in many countries, including the Indian private sector.
      The cost and impact of using serology compared with other diagnostic techniques
      is unknown. METHODS AND FINDINGS: Taking a patient cohort conservatively equal to
      the annual number of serological tests done in India (1.5 million adults
      suspected of having active TB), we used decision analysis to estimate costs and
      effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy
      plus automated liquid culture (mycobacterium growth indicator tube [MGIT],
      US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test
      accuracy and costs were obtained from published literature. We adopted the
      perspective of the Indian TB control sector and an analysis frame of 1 year. Our
      primary outcome was the incremental cost per disability-adjusted life year (DALY)
      averted. We performed one-way sensitivity analysis on all model parameters, with
      multiway sensitivity analysis on variables to which the model was most sensitive.
      If used instead of sputum microscopy, serology generated an estimated 14,000 more
      TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs
      averted, and 32,000 more secondary TB cases than microscopy, at approximately
      four times the incremental cost (US$47.5 million versus US$11.9 million). When
      added to high-quality sputum smears, MGIT culture was estimated to avert 130,000
      incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was
      dominated by (i.e., more costly and less effective than) MGIT culture and
      remained less economically favorable than sputum smear or TB culture in one-way
      and multiway sensitivity analyses. CONCLUSIONS: In India, sputum smear microscopy
      remains the most cost-effective diagnostic test available for active TB; efforts
      to increase access to quality-assured microscopy should take priority. In areas
      where high-quality microscopy exists and resources are sufficient, MGIT culture
      is more cost-effective than serology as an additional diagnostic test for TB.
      These data informed a recently published World Health Organization policy
      statement against serological tests.

PMID- 21857811
TI  - Changes in drug utilization during a gap in insurance coverage: an examination of
      the medicare Part D coverage gap.
AB  - BACKGROUND: Nations are struggling to expand access to essential medications
      while curbing rising health and drug spending. While the US government's Medicare
      Part D drug insurance benefit expanded elderly citizens' access to drugs, it also
      includes a controversial period called the "coverage gap" during which
      beneficiaries are fully responsible for drug costs. We examined the impact of
      entering the coverage gap on drug discontinuation, switching to another drug for
      the same indication, and drug adherence. While increased discontinuation of and
      adherence to essential medications is a regrettable response, increased switching
      to less expensive but therapeutically interchangeable medications is a positive
      response to minimize costs. METHODS AND FINDINGS: We followed 663,850 Medicare
      beneficiaries enrolled in Part D or retiree drug plans with prescription and
      health claims in 2006 and/or 2007 to determine who reached the gap spending
      threshold, n = 217,131 (33%). In multivariate Cox proportional hazards models, we
      compared drug discontinuation and switching rates in selected drug classes after
      reaching the threshold between all 1,993 who had no financial assistance during
      the coverage gap (exposed) versus 9,965 multivariate propensity score-matched
      comparators with financial assistance (unexposed). Multivariate logistic
      regressions compared drug adherence (<= 80% versus >80% of days covered).
      Beneficiaries reached the gap spending threshold on average 222 d +/-79. At the
      drug level, exposed beneficiaries were twice as likely to discontinue (hazard
      ratio [HR]  = 2.00, 95% confidence interval [CI] 1.64-2.43) but less likely to
      switch a drug (HR  = 0.60, 0.46-0.78) after reaching the threshold. Gap-exposed
      beneficiaries were slightly more likely to have reduced adherence (OR  = 1.07,
      0.98-1.18). CONCLUSIONS: A lack of financial assistance after reaching the gap
      spending threshold was associated with a doubling in discontinuing essential
      medications but not switching drugs in 2006 and 2007. Blunt cost-containment
      features such as the coverage gap have an adverse impact on drug utilization that
      may conceivably affect health outcomes.

PMID- 21857812
TI  - Computation of Absolute Hydration and Binding Free Energy with Free Energy
      Perturbation Distributed Replica-Exchange Molecular Dynamics (FEP/REMD).
AB  - Distributed Replica (REPDSTR) is a powerful parallelization technique enabling
      simulations of a group of replicas in a parallel/parallel fashion, where each
      replica is distributed to different nodes of a large cluster [Theor. Chem. Acc.
      109: 140 (2003)]. Here, we use the framework provided by REPDSTR to combine a
      staged free energy perturbation protocol with different values of the
      thermodynamic coupling parameters with replica-exchange molecular dynamics
      (FEP/REMD. The structure of REPDSTR, which allows multiple parallel input/output
      (I/O), facilitates the treatment of replica-exchange to couple the N window
      simulations. As a result, each of the N synchronous window simulations benefit
      from the sampling carried out by the N-1 others. As illustrative examples of the
      FEP/REMD strategy, calculations of the absolute hydration and binding free energy
      of small molecules were performed using the biomolecular simulation program
      CHARMM adapted for the IBM Blue Gene/P platform. The computations show that a
      FEP/REMD strategy significantly improves the sampling and accelerate the
      convergence of absolute free energy computations.

PMID- 21857813
TI  - Free Energy Perturbation Hamiltonian Replica-Exchange Molecular Dynamics (FEP/H
      REMD) for Absolute Ligand Binding Free Energy Calculations.
AB  - Free Energy Perturbation with Replica Exchange Molecular Dynamics (FEP/REMD)
      offers a powerful strategy to improve the convergence of free energy
      computations. In particular, it has been shown previously that a FEP/REMD scheme
      allowing random moves within an extended replica ensemble of thermodynamic
      coupling parameters "lambda" can improve the statistical convergence in
      calculations of absolute binding free energy of ligands to proteins [J. Chem.
      Theory Comput. 2009, 5, 2583]. In the present study, FEP/REMD is extended and
      combined with an accelerated MD simulations method based on Hamiltonian replica
      exchange MD (H-REMD) to overcome the additional problems arising from the
      existence of kinetically trapped conformations within the protein receptor. In
      the combined strategy, each system with a given thermodynamic coupling factor
      lambda in the extended ensemble is further coupled with a set of replicas
      evolving on a biased energy surface with boosting potentials used to accelerate
      the inter-conversion among different rotameric states of the side chains in the
      neighborhood of the binding site. Exchanges are allowed to occur alternatively
      along the axes corresponding to the thermodynamic coupling parameter lambda and
      the boosting potential, in an extended dual array of coupled lambda- and H-REMD
      simulations. The method is implemented on the basis of new extensions to the
      REPDSTR module of the biomolecular simulation program CHARMM. As an illustrative
      example, the absolute binding free energy of p-xylene to the nonpolar cavity of
      the L99A mutant of T4 lysozyme was calculated. The tests demonstrate that the
      dual lambda-REMD and H-REMD simulation scheme greatly accelerates the
      configurational sampling of the rotameric states of the side chains around the
      binding pocket, thereby improving the convergence of the FEP computations.

PMID- 21857814
TI  - Application of Molecular Dynamics Simulations in Molecular Property Prediction I:
      Density and Heat of Vaporization.
AB  - Molecular mechanical force field (FF) methods are useful in studying condensed
      phase properties. They are complementary to experiment and can often go beyond
      experiment in atomic details. Even a FF is specific for studying structures,
      dynamics and functions of biomolecules, it is still important for the FF to
      accurately reproduce the experimental liquid properties of small molecules that
      represent the chemical moieties of biomolecules. Otherwise, the force field may
      not describe the structures and energies of macromolecules in aqueous solutions
      properly. In this work, we have carried out a systematic study to evaluate the
      General AMBER Force Field (GAFF) in studying densities and heats of vaporization
      for a large set of organic molecules that covers the most common chemical
      functional groups. The latest techniques, such as the particle mesh Ewald (PME)
      for calculating electrostatic energies, and Langevin dynamics for scaling
      temperatures, have been applied in the molecular dynamics (MD) simulations. For
      density, the average percent error (APE) of 71 organic compounds is 4.43% when
      compared to the experimental values. More encouragingly, the APE drops to 3.43%
      after the exclusion of two outliers and four other compounds for which the
      experimental densities have been measured with pressures higher than 1.0 atm. For
      heat of vaporization, several protocols have been investigated and the best one,
      P4/ntt0, achieves an average unsigned error (AUE) and a root-mean-square error
      (RMSE) of 0.93 and 1.20 kcal/mol, respectively. How to reduce the prediction
      errors through proper van der Waals (vdW) parameterization has been discussed. An
      encouraging finding in vdW parameterization is that both densities and heats of
      vaporization approach their "ideal" values in a synchronous fashion when vdW
      parameters are tuned. The following hydration free energy calculation using
      thermodynamic integration further justifies the vdW refinement. We conclude that
      simple vdW parameterization can significantly reduce the prediction errors. We
      believe that GAFF can greatly improve its performance in predicting liquid
      properties of organic molecules after a systematic vdW parameterization, which
      will be reported in a separate paper.

PMID- 21857816
TI  - Categorial compositionality II: universal constructions and a general theory of
      (quasi-)systematicity in human cognition.
AB  - A complete theory of cognitive architecture (i.e., the basic processes and modes
      of composition that together constitute cognitive behaviour) must explain the
      systematicity property--why our cognitive capacities are organized into
      particular groups of capacities, rather than some other, arbitrary collection.
      The classical account supposes: (1) syntactically compositional representations;
      and (2) processes that are sensitive to--compatible with--their structure.
      Classical compositionality, however, does not explain why these two components
      must be compatible; they are only compatible by the ad hoc assumption
      (convention) of employing the same mode of (concatenative) compositionality
      (e.g., prefix/postfix, where a relation symbol is always prepended/appended to
      the symbols for the related entities). Architectures employing mixed modes do not
      support systematicity. Recently, we proposed an alternative explanation without
      ad hoc assumptions, using category theory. Here, we extend our explanation to
      domains that are quasi-systematic (e.g., aspects of most languages), where the
      domain includes some but not all possible combinations of constituents. The
      central category-theoretic construct is an adjunction involving pullbacks, where
      the primary focus is on the relationship between processes modelled as functors,
      rather than the representations. A functor is a structure-preserving map (or
      construction, for our purposes). An adjunction guarantees that the only pairings
      of functors are the systematic ones. Thus, (quasi-)systematicity is a necessary
      consequence of a categorial cognitive architecture whose basic processes are
      functors that participate in adjunctions.

PMID- 21857819
TI  - Gastro-hep news.

PMID- 21857817
TI  - C-terminal region of EBNA-2 determines the superior transforming ability of type
      1 Epstein-Barr virus by enhanced gene regulation of LMP-1 and CXCR7.
AB  - Type 1 Epstein-Barr virus (EBV) strains immortalize B lymphocytes in vitro much
      more efficiently than type 2 EBV, a difference previously mapped to the EBNA-2
      locus. Here we demonstrate that the greater transforming activity of type 1 EBV
      correlates with a stronger and more rapid induction of the viral oncogene LMP-1
      and the cell gene CXCR7 (which are both required for proliferation of EBV-LCLs)
      during infection of primary B cells with recombinant viruses. Surprisingly,
      although the major sequence differences between type 1 and type 2 EBNA-2 lie in N
      terminal parts of the protein, the superior ability of type 1 EBNA-2 to induce
      proliferation of EBV-infected lymphoblasts is mostly determined by the C-terminus
      of EBNA-2. Substitution of the C-terminus of type 1 EBNA-2 into the type 2
      protein is sufficient to confer a type 1 growth phenotype and type 1 expression
      levels of LMP-1 and CXCR7 in an EREB2.5 cell growth assay. Within this region,
      the RG, CR7 and TAD domains are the minimum type 1 sequences required. Sequencing
      the C-terminus of EBNA-2 from additional EBV isolates showed high sequence
      identity within type 1 isolates or within type 2 isolates, indicating that the
      functional differences mapped are typical of EBV type sequences. The results
      indicate that the C-terminus of EBNA-2 accounts for the greater ability of type 1
      EBV to promote B cell proliferation, through mechanisms that include higher
      induction of genes (LMP-1 and CXCR7) required for proliferation and survival of
      EBV-LCLs.

PMID- 21857818
TI  - Population Colorectal Cancer Screening Estimates: Comparing Self-Report to
      Electronic Health Record Data in California.
AB  - INTRODUCTION: Population-based surveys are used to assess colorectal cancer (CRC)
      screening rates, but may be subject to self-report biases. Clinical data from
      electronic health records (EHR) are another data source for assessing screening
      rates and self-report bias; however, use of EHR data for population research is
      relatively new. We sought to compare CRC screening rates from a self-report
      survey, the 2007 California Health Interview Survey (CHIS), to EHR data from Palo
      Alto Medical Foundation (PAMF), a multi-specialty healthcare organization serving
      three counties in California.  METHODS: Ever- and up-to-date CRC screening rates
      were compared between CHIS respondents (N=18,748) and PAMF patients (N=26,283).
      Both samples were limited to English proficient subjects aged 51-75 with health
      insurance and a physician visit in the past two years. PAMF rates were age-sex
      standardized to the CHIS population. Analyses were stratified by racial/ethnic
      group.  RESULTS: EHR data included PAMF internally completed tests (84%), and
      patient-reported externally completed tests which were either confirmed (7%) or
      unconfirmed (9%) by a physician. When excluding unconfirmed tests, PAMF screening
      rates were 6-14 percentage points lower than CHIS rates, for both ever- and up-to
      date CRC screening among Non-Hispanic White, Black, Hispanic/Latino, Chinese,
      Filipino and Japanese subjects. When including unconfirmed tests, differences in
      screening rates between the two data sets were minimal.  CONCLUSION:
      Comparability of CRC screening rates from survey data and clinic-based EHR data
      depends on whether or not unconfirmed patient-reported tests in EHR are included.
      This indicates a need for validated methods of calculating CRC screening rates in
      EHR data.

PMID- 21857822
TI  - Surgical risks in patients on inflammatory bowel disease medications.

PMID- 21857821
TI  - Extraintestinal manifestations of inflammatory bowel disease.
AB  - Extraintestinal manifestations of inflammatory bowel disease are prevalent in
      both ulcerative colitis and Crohn's disease. The most common manifestations
      involve the musculoskeletal and dermatologic systems. Other manifestations
      involve the hepatopan-creatobiliary system (eg, primary sclerosing cholangitis)
      as well as the ocular, renal, and pulmonary systems. A multidisciplinary team
      approach is often needed for effective management, and emergency situations
      require prompt evaluation.

PMID- 21857820
TI  - Current concepts in the pathophysiology and management of hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological
      dysfunction in patients with acute or chronic liver disease and/or portosystemic
      shunting of blood flow. The pathophysiology of this disease is quite complex, as
      it involves overproduction and reduced metabolism of various neurotoxins,
      particularly ammonia. Recent hypotheses implicate low-grade cerebral edema as a
      final common pathway for the pathophysiology of HE. Management of this condition
      is multifaceted and requires several steps: elimination of precipitating factors;
      removal of toxins, both by reducing them at their source and by augmenting
      scavenging pathways; modulation of resident fecal flora; proper nutritional
      support; and downregulation of systemic and gut-derived inflammation.

PMID- 21857823
TI  - Endoscopic mucosal resection.

PMID- 21857824
TI  - Pancrelipase delayed-release capsules for the treatment of pancreatic
      insufficiency.

PMID- 21857825
TI  - Immunoglobulin g4-associated autoimmune cholangiopathy.

PMID- 21857826
TI  - Clinical presentation and treatment of pediatric patients with eosinophilic
      esophagitis.

PMID- 21857827
TI  - Gastrointestinal Bleeding Due to a Dieulafoy Lesion in the Afferent Limb of a
      Billroth II Reconstruction.

PMID- 21857829
TI  - Gastro-hep news.

PMID- 21857828
TI  - Dieulafoy-like lesion bleeding: in the loop.

PMID- 21857830
TI  - Searching for the delta: 5-aminosalicylic Acid therapy for Crohn's disease.
AB  - Crohn's disease (CD) is a chronic inflammatory condition that often requires
      lifelong medical therapy for the induction and maintenance of remission. Oral
      mesalamine (5-aminosalicylic acid [5-ASA]) therapy has several forms, which can
      be categorized into oral formulations and prodrugs. The ability to demonstrate
      the efficacy of 5-ASA is limited in most clinical trials by the nonspecific
      endpoints of the Crohn's Disease Activity Index. Overall, clinical trials have
      not shown 5-ASA therapy to be superior to placebo for the induction of remission,
      with the exception of sulfasalazine in colonic CD. 5-ASA therapy has also not
      been shown to be superior to placebo for maintenance of medically induced
      remission; however, mesalamine may have a modest effect in surgically induced
      remission. Further research is needed regarding the optimal monitoring and
      therapy for patients with mild CD who often achieve remission with placebo in
      clinical trials.

PMID- 21857831
TI  - Ethnic disparities in liver transplantation.
AB  - End-stage liver disease is a major cause of morbidity and mortality among ethnic
      minorities. In the United States, ethnic minorities comprise approximately 30% of
      all adult liver transplantations performed annually. Several studies have
      suggested that ethnic populations differ with respect to access and outcomes in
      the pre- and post-transplantation setting. This paper will review the existing
      literature on ethnic variations in the adult liver transplantation population.

PMID- 21857832
TI  - Management of Dysphagia in stroke patients.

PMID- 21857833
TI  - Irreversible electroporation for treatment of liver cancer.

PMID- 21857834
TI  - Why should we define and target early Crohn's disease?

PMID- 21857835
TI  - The significance and management of nonampullary duodenal polyps.

PMID- 21857836
TI  - Autoimmune cholangiopathy and high-output heart failure in a patient with graves
      disease.

PMID- 21857837
TI  - Hepatic dysfunction in hyperthyroidism.

PMID- 21857838
TI  - Barrett esophagus with progression to adenocarcinoma in multiple family members
      with attenuated familial polyposis.

PMID- 21857839
TI  - Germline APC Mutation and Familial Barrett Esophagus: Causal or Coincidence?

PMID- 21857840
TI  - A Bayesian Approach for Investigating the Risk of QT Prolongation.
AB  - The standard approach to investigating a drug for its potential for QT
      prolongation is to construct a 90% two-sided (or a 95% one-sided) confidence
      interval (CI), for the difference in baseline corrected mean QTc (heart-rate
      corrected version of QT) between drug and placebo at each time-point, and to
      conclude non-inferiority if the upper limit for each CI is less than a pre
      specified constant. An alternative approach is to base the non-inferiority
      inference on the largest difference in population mean QTc (baseline corrected)
      between drug and placebo. In this paper, we propose a Bayesian approach to
      resolving this problem using a Monte Carlo simulation method. We use simulated
      data to assess the performance of the proposed approach, discuss its advantages
      over the standard approach, and illustrate the method by applying it to a real
      data set obtained from a thorough QT study conducted at GlaxoSmithKline (GSK).

PMID- 21857842
TI  - Molecular monitoring of resistant dhfr and dhps allelic haplotypes in Morogoro
      and Mvomero districts in south eastern Tanzania.
AB  - BACKGROUND: Resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP)
      emerged in Plasmodium falciparum from Asia in the 1960s and subsequently spread
      to Africa. In Tanzania, SP use as a national policy began in 1983 as a second
      line to chloroquine (CQ) for the treatment of uncomplicated malaria, until August
      2001 when it was approved to replace CQ as a national first line. OBJECTIVE: The
      present study assesses the frequency of resistant dhfr and dhps alleles in
      Morogoro-Mvomero district in south eastern Tanzania and contrast their rate of
      change during 17 years of SP second line use against five years of SP first line
      use. METHODOLOGY: Cross sectional surveys of asymptomatic infections were carried
      out at the end of rainy season during July-September of 2000, when SP was the
      national second line (CQ was the first line) and 2006 when SP was the national
      first line antimalarial treatment. Genetic analysis of SP resistance genes was
      carried out on 1,044 asymptomatic infections and the effect of the two policies
      on SP evolution compared. RESULTS: The frequency of the most resistant allele,
      the double dhps-triple dhfr mutant genotype, increased by only 1% during 17 years
      of SP second line use, but there was a dramatic increase by 45% during five years
      of SP first line use. CONCLUSION: We conclude that National policy change from
      second line to first line SP, brought about an immediate shift in treatment
      practice and this in turn had a highly significant impact on drug pressure. The
      use of SP in specific programs only such as intermittent preventive treatment of
      infants (IPTi) and intermittent preventive treatment of pregnant women (IPTp)
      will most likely reduce substantially SP selection pressure and the SP resistance
      alleles alike.

PMID- 21857843
TI  - Evaluation of the LTK63 adjuvant effect on cellular immune responses to measles
      virus nucleoprotein.
AB  - BACKGROUND: A lot of pathogens enter the body via the nasal route. The
      construction of non-toxic mutants of heat labile Escherichia coli enterotoxin
      (LT), which is a potent mucosal adjuvant, represents a major breakthrough for the
      development of mucosal vaccines. OBJECTIVE: This study was undertaken to
      critically evaluate the adjuvanticity of the mutant of LT (LTK63) on the cellular
      immune responses to intranasally co-administered recombinant measles virus
      nucleoprotein (rMVNP). METHODS: Groups of CBA mice were immunized intranasally
      with rMVNP with or without LT or LTK63 as adjuvants. Another group was immunized
      subcutaneously with rMVNP in Freund's adjuvant. rMVNP and measles virus (MV) were
      used in a proliferation assay to test the LTK63 potentiating ability to induce T
      cell responses. Subsequently MVNP synthetic peptides spanning the length of the N
      protein were used with a proliferation assay to identify the T cell epitopes.
      RESULTS: Splenocytes from mice immunized intranasally with rMVNP plus LT or
      LTK63, showed strong dose dependent proliferative responses to both the MVNP and
      MV. However, proliferative responses from the latter group were significantly
      lower than the former group (P < 0.05). Splenocytes tested recognized peptides
      20, 21, 28, 31, 39, 40 and 50, suggesting these to be among important epitopes.
      Subcutaneous route was not effective in priming for T cell responses to rMVNP.
      CONCLUSION: These data further demonstrate the great potential of LTK63 as a safe
      mucosal vaccine adjuvant.

PMID- 21857844
TI  - Seroprevalence and determinants of human herpes virus 8 infection in adult
      Nigerians with and without HIV-1 infection.
AB  - BACKGROUND: There is a dearth of studies on HHV8-HIV co-infections from Nigeria,
      even as both infections have been shown to be endemic in Africa. This study
      examined the seroprevalence and determinants of HHV8 infections in adult
      Nigerians with and without HIV-infection. METHODS: In 2007, a cross sectional
      study undertaken in a tertiary hospital in Zaria, northern Nigeria enrolled 71
      HIV-1 positive adults without Kaposi's sarcoma and 85 apparently healthy HIV
      negative adult volunteers of the general population. Anti-lytic antibodies to
      HHV8 infection was determined by ELISA. A univariate analysis including age, sex,
      marital status, past sexually transmitted disease (STD), past blood transfusion,
      HIV/AIDS staging and CD4 count was used to determine variables associated with
      HHV8 seropositivity. Significant variables were adjusted in a logistic regression
      model expressed in odds ratio (OR) with 95% confidence interval (CI). P<0.05 was
      considered significant RESULTS: The seroprevalence of HHV8 infection was 62% in
      HIV-1 positive patients and 25.9% in HIV negative adults (p<0.001). A past
      history of STD [OR= 2.88, 95% CI= 1.0 - 8.2] and advanced HIV/AIDS (WHO stage 3
      and 4) [OR=3.5, 95% CI= 1.21-10.1] were the only variables independently
      associated with HHV8 seropositivity in HIV-infected patients. In HIV-negative
      adults, none of the variables was significantly associated with HHV8
      seropositivity. CONCLUSION: The study findings suggest an adverse interaction
      between HHV8 and HIV-1. The higher prevalence of HHV8 infection in HIV-infected
      patients and its association with STD support a predominant sexual route of HHV8
      transmission among adult Nigerians.

PMID- 21857845
TI  - Clinical and prognostic features of patients with pandemic 2009 influenza A
      (H1N1) virus in the intensive care unit.
AB  - OBJECTIVE: To investigate the clinical and prognostic features of patients
      admitted to intensive care unit (ICU) with pandemic 2009 influenza A (H1N1)
      virus. METHODS: Patients admitted to the intensive care unit for severe pneumonia
      associated with pandemic 2009 influenza A (H1N1) virus were evaluated. RESULTS:
      The study included 20 patients with the mean age of 36+/-13. Of the 20 subjects,
      17 (85%) had underlying conditions. Of the 20 patients, 11(55%) were discharged
      and 9 (45%) died. Cardinal symptoms were fever, myalgia, and hemoptysis with the
      rates of 85 %, 75 % and 45 %, respectively. All patients had pneumonic
      infiltrations in their chest roentgenograms. Main laboratory findings were
      lymphopenia, high creatin phosphokinase (CPK) and Lactate dehydrogenase (LDH)
      levels. All patients had positivity on real time reverse transcription-polymerase
      chain reaction (RT-PCR). None of the patients had pandemic 2009 influenza A
      (H1N1) virus vaccination. None of them had taken oseltamivir within 48 hours.
      Main reasons for mortality were cardiovascular complications and ventilatory
      associated pneumonia due to Acynetobacter baumannii. CONCLUSION: Early diagnosis
      and antiviral treatment in these cases seem to be the best approach to avoid
      serious illness. Special attention should be given to patients having underlying
      conditions such as cardiovascular and pulmonary diseases and pregnancy.

PMID- 21857846
TI  - Pandemic Influenza A (H1N1): knowledge among senior health workers at a secondary
      health care institution in Southwest, Nigeria.
AB  - OBJECTIVE: This study was conducted to assess the level of knowledge of influenza
      A (H1N1) infection among health care workers in a secondary health care facility
      in Osogbo, Southwest Nigeria. METHODS: A structured questionnaire assessing
      participants'knowledge of swine influenza viruses, mode of transmission, clinical
      criteria, primary prevention, indications for emergency care, care of affected
      persons and ongoing pandemic of Influenza A H1N1 was hand-delivered to all senior
      health care workers working in the hospital. RESULTS: The mean age of the
      respondents was 40.4+/-9.6 years. The majority (59.3%) were females. Television
      (73.6%) radio (61.5%), newspapers (44%), other health workers (31.9%), and
      internet (15.4%) were the main sources of information about influenza A H1N1.
      Nearly all (92.3%) felt that their source of information about the disease was
      inadequate. About half (51.6%) knew the virus can be transmitted from one person
      to another. Majority identified correctly the symptoms of infected victims such
      as fever (83.5%), and runny nose (79.1%). Most (87.9%) identified hand washing
      with soap and water as a mode of preventing transmission. Most (83.5%) felt an
      infected person should be isolated while very few knew oseltamivir (13.2%) and
      zanamivir (17.6%) are drugs to treat. Multivariate linear regression analysis
      identified, male sex (p=0.029), internet as a source of information (p=0.029) and
      knowledge of prevention of H1N1 (p= 0.005) as factors that were significantly
      associated with a high knowledge score on the current pandemic. CONCLUSION: There
      is a need to provide comprehensive information to health workers on the current
      pandemic.

PMID- 21857847
TI  - Nasal carriage of multi-drug resistant Staphylococcus aureus in healthy
      inhabitants of Amassoma in Niger delta region of Nigeria.
AB  - BACKGROUND: Nasal Staphylococcus aureus is a major source of community and
      hospital associated staphylococcal infections. This study determined the
      prevalence of nasal S. aureus isolates and investigated their antimicrobial
      resistance profile in healthy volunteers. METHODS: Nasal specimens of healthy
      volunteers in Amassoma were cultured and screened for S. aureus using standard
      microbiological protocols and their antibiotic profile susceptibility was
      investigated using disc diffusion and agar dilution techniques. RESULTS: A total
      of 40 (33.3%) S. aureus isolates were obtained from 120 nares specimens screened.
      Twenty three (57.5%) and 17 (42.5%) of the isolates were from university students
      and villagers respectively. The isolates showed an overall 75% resistance to
      ampicillin, 52.5% to doxycycline, 47.5% to chloramphenicol, 35% to erythromycin
      and 32.5% to cotrimoxazole; with 27.5% methicillin resistant. No isolate was
      resistant to gentamicin while few isolates were resistant to cefuroxime (2.5%),
      augmentin (5.0%), ciprofloxacin (10.0%), ofloxacin (10.0%) and vancomycin (7.5%).
      Twenty one (52.5%) of all the isolates were multi-drug resistant, ten (47.6%) of
      which were methicillin resistant Staphylococcus aureus (MRSA) and only 3 (7.5%)
      were fully susceptible to all the tested antimicrobial drugs. CONCLUSIONS: The
      observation calls for strategies to prevent their spread to more vulnerable
      populations where the consequences of their infections can be severe.

PMID- 21857848
TI  - Bacteriuria among adult non-pregnant women attending Mulago hospital assessment
      centre in Uganda.
AB  - BACKGROUND: Urinary tract infections (UTIs) in women are a common problem in
      primary health care settings. Resistance of bacterial uropathogens to commonly
      used antibiotics is common in many places. OBJECTIVES: To determine the
      prevalence of UTI, associated uropathogens and their antimicrobial
      susceptibility. METHODS: A cross section study carried out at Mulago hospital
      outpatients' department. Midstream urine samples (MSU) were collected from 399
      women, who gave informed consent and fulfilled other study criteria. Quantitative
      culture method, identification of uropathogens and antibiotic susceptibility
      testing using the Kirby-Bauer disc diffusion technique were applied to the
      isolates. RESULTS: Out of 399 MSU samples, 40 pure significant bacterial growths
      (>=10(5) colony forming units (cfu)/ml of urine) were isolated and these included
      Escherichia coli, 23 (57.5%), Staphylococcus aureus, 9 (22.5%), Enterococci spp,
      6 (15%) and Klebsiella pneumoniae, 2 (5.0%). Overall, sensitivities were:
      nitrofurantoin (98.3%), cefuroxime (89.3%), and cotrimoxazole (20%) by all
      uropathogens isolated. CONCLUSIONS: Culture positive UTI among adult non-pregnant
      women are a common problem, occurring in 10% of the study population. Most
      bacterial uropathogens showed high sensitivity to nitrofurantoin but low
      sensitivity to SXT. RECOMMENDATIONS: Nitrofurantoin should be considered as drug
      of choice for empirical treatment of community acquired uncomplicated UTI in
      adult non-pregnant women.

PMID- 21857849
TI  - Low tuberculosis case detection in Gokwe North and South, Zimbabwe in 2006.
AB  - BACKGROUND: Case detection is an important component of tuberculosis control
      programmes. It helps identify sources of infection, treat them, and thus break
      the chain of infection. OBJECTIVE: To determine the reasons of low tuberculosis
      case detection in Gokwe Districts, Zimbabwe. METHODS: A descriptive cross
      sectional study was conducted. We used interviewer administered questionnaire for
      nurses and patients, checklists, key informant interviews. RESULTS: Thirty-eight
      nurses, forty-two patients and seven key informants were interviewed and 1254
      entries in tuberculosis register were reviewed. Nurses correctly defined
      pulmonary tuberculosis, listed signs and symptoms, preventive measures and
      methods of tuberculosis diagnosis. Exit interviews showed 9/42 (21%) of patients
      presenting with cough were asked to submit sputa for examination and asked about
      household contacts with tuberculosis. About 27% of patients who were sputum
      positive in the laboratory register were not recorded in the district
      tuberculosis register. This contributed to the high proportion of early
      defaulters among tuberculosis suspects. CONCLUSION: Low tuberculosis case
      detection was because nurses were not routinely requesting for sputum for
      examination in patients presenting with a cough or history of previous treatment
      for cough. Nurses should routinely request for sputum for examination in patients
      presenting with a cough or history of recent treatment for cough.

PMID- 21857850
TI  - Evaluation of the physicochemical equivalence of three brands of commercially
      available quinine sulphate tablets from South Western part of Nigeria.
AB  - BACKGROUND: The relatively little resistance to quinine globally has led to an
      increase in its use in P. falciparum malaria especially in multi-drug resistant
      strains. OBJECTIVE: To evaluate the physicochemical and equivalency of three
      brands of quinine sulphate tablets available in South Western region of Nigeria.
      METHODS: The pharmaceutical and chemical equivalence of three brands of quinine
      sulphate tablets were assessed through the evaluation of some biopharmaceutical
      parameters and active drug content. RESULTS: All the brands complied with the
      official specification for uniformity of weight. Two of the brands (A & B) gave
      similar crushing strengths while the third brand (C) gave a much lower value.
      Similarly all the brands complied with the official specification of
      disintegration test but the obtained values were statistically different
      (p<0.05). The T(70) obtained from the dissolution rate profile was less than 45
      minutes for the three brands, although A and B were not statistically different
      but C was statistically from A and B. The quinine content of brands B and C are
      within the official specification however brand A with percentage content of
      110+/-1.3%w/w, is above the specification while it is statistically different
      from the other brands. CONCLUSION: Brands B and C could be regarded as chemical
      equivalent, but they are not biopharmaceutical equivalents, on the other hand,
      brands A and B may be regarded as biopharmaceutical equivalents but not chemical
      equivalent.

PMID- 21857851
TI  - Age, poverty and alcohol use as HIV risk factors for women in Mongu, Zambia.
AB  - BACKGROUND: Age, poverty and alcohol use are seen as risk factors for HIV among
      women in sub-Saharan Africa. OBJECTIVE: The objective of this study was to
      understand the influence of socioeconomic factors (including age and poverty) as
      well as alcohol use on risky sexual behaviors among women in Mongu, Zambia.
      METHODS: This study examines these factors in the local context of Mongu, Zambia
      using the Priorities for Local AIDS Control Efforts (PLACE) methodology. This
      methodology allows for the study of risky behaviors while taking into
      consideration local factors. The two outcome variable studied were transactional
      sex in the past year and having two or more sexual partners in the past year.
      RESULTS: In this study age was not a significant factor, but alcohol use and
      poverty/desire for economic advancement were significant factors. CONCLUSION:
      Programs and policies need to address the influence of alcohol on risky sexual
      behaviors and also the important but complex influence of poverty.

PMID- 21857852
TI  - Sexual, reproductive health needs and rights of young people with perinatally
      acquired HIV in Uganda.
AB  - BACKGROUND: Numbers of young people with perinatally acquired HIV is growing
      significantly. With antiretroviral drugs, children who get infected at birth with
      HIV have an opportunity to graduate into adolescence and adulthood. This
      achievement notwithstanding, new challenges have emerged in their care and
      support needs. The most dynamic being, their sexual and reproductive health needs
      and rights (SRHR). OBJECTIVES: This paper aimed at establishing the gaps at
      policy, program and health systems level as far as addressing sexual and
      reproductive health needs of young people who have lived with HIV since infancy
      is concerned. METHODS: This paper is based on a desk review of existing
      literature on sexual and reproductive health needs and rights of young positives.
      RESULTS: The results indicate young positives are sexually active and are
      engaging in risky sexual encounters. Yet, existing policies, programs and
      services are inadequate in responding to their sexual and reproductive health
      needs and rights. CONCLUSION: Against these findings, it is important, that
      policies specifically targeting this subgroup are formulated and to make sure
      that such policies result in programs and services that are youth friendly. It is
      also important that integration of Sexual Reproductive Health (SRH) and HIV
      services is prioritized.

PMID- 21857853
TI  - Suicide in urban Kampala, Uganda: a preliminary exploration.
AB  - BACKGROUND: Suicide was investigated in the urban setting of Kampala, Uganda.
      OBJECTIVES: Firstly, to explore the use of two research methodologies, a
      retrospective review of patient records and the psychological autopsy methodology
      in suicide research in Uganda. Secondly to investigate the characteristics and
      correlates of urban suicide in Uganda. RESULTS: A male to female ratio of suicide
      of 3.4:1 and a peak age of suicide in the 20-39 years age group were found. The
      main methods of suicide were hanging and ingestion of poison (organophosphates).
      Problems with social networks, negative life events, higher psychological
      distress and lower quality of life were associated with suicide at univariate
      analysis. It was only psychological distress that retained significance at
      multivariate analysis. CONCLUSION: The retrospective review of records at Mulago
      hospital was beset by incomplete records whereas a pilot psychological autopsy
      study was well accepted and might contribute valuable data in African settings.

PMID- 21857854
TI  - Predictors of psychopathology among Nigerian adolescents: the role of
      psychosocial, demographics, personality and medical condition reports domains.
AB  - BACKGROUND: Psychopathology among adolescents has become a global concern in the
      last decade. OBJECTIVE: The aim of this study was to identify the predictors of
      psychopathology among adolescents in Ibadan region using a multi-theoretical
      approach. METHODS: Eight hundred and eighty-nine (889) male and female
      adolescents drawn from different parts of Ibadan region of the South-West
      Nigeria, participated in the study. The study is a cross-sectional survey and
      adopted an ex-post facto design. A questionnaire divided into six sections, with
      two versions was used for data collection. Analysis of data involved
      multiple/stepwise regressions, F-test & T-test. SPSS 10.0 computer programme was
      utilized for all analyses. RESULTS: Data showed that all the predictors jointly
      contributed 37% (P<0.0001) to the prediction of reported psychopathology. The
      domains of psychosocial, personality, demographic and medical condition reports
      all independently and significantly predicted psychopathology among the
      adolescents but psychosocial domain had the highest contribution of 16%
      (P<0.0001). Prevalence rate for psychopathology among the sampled adolescents was
      0.152 (15.2%) at the criteria of one standard deviation above the mean.
      CONCLUSION: It is concluded that a multi-theoretical approach to the
      understanding of psychopathology among adolescents will be more appropriate in
      the Nigerian community. Results have implication for further assessment and
      treatments. Parents are advised to report any behavioural dysfunction observed in
      their wards to experts early enough to avoid degeneration to greater
      psychopathology in the later years.

PMID- 21857855
TI  - Reference values for serum levels of folic acid and vitamin B12 in a young adult
      Ugandan population.
AB  - INTRODUCTION: Reference values may vary significantly among populations and
      cultures for which dietary intakes may be different. Each laboratory is expected
      to investigate the transferability of the expected values to its own patient
      population and if necessary determine its own reference ranges. This study sought
      to establish Folic acid and Vitamin B(12) reference values for young Ugandan
      adults, which reference values could be used as baseline information for future
      research, especially related to their role in breast cancer prevention. METHODS:
      A cross sectional study in which 200 undergraduate student volunteers were
      enrolled. The minimum sample size was 126 using the Open Epi version 2. Relevant
      demographics and physical examination parameters were taken as well as blood
      samples for laboratory tests. Prior ethical approval was granted. RESULTS: The
      levels of folic acid were 4.17 - 20 ng/ml and remained constant over the age
      cohorts. The vitamin B(12) range was 117-1158 pg/ml. Both ranges were comparable
      to ranges seen in other populations. CONCLUSION: In as much as the dietary intake
      for this study population is presumed different from populations in the western
      countries, the ranges for these two vitamins were similar.

PMID- 21857856
TI  - Micturitional dryness and attitude of parents towards enuresis in children
      attending outpatient unit of a tertiary hospital in Abeokuta, Southwest Nigeria.
AB  - BACKGROUND: There is significant variability of the age at which children achieve
      dryness. OBJECTIVES: We determine the age at achievement of micturational dryness
      and attitude of parents about enuresis among urban Nigerian children. METHOD: A
      total of 346 questionnaires were administered to parents of children between the
      ages of 12 - 180 months who came for routine paediatric care at the outpatient
      unit of Federal Medical Centre, Abeokuta. RESULTS: At age 36 months, 86 (51.8 %)
      and 34 (20.5 %) out of 166 children had achieved dryness at daytime and night
      time respectively. Achievement of dryness was significantly related to low
      maternal education (p = 0.022) and low social class (p = 0.009). Twenty-four
      (26.7 %) children had nocturnal enuresis. Four (4.4 %) of these children also had
      diurnal enuresis. All the parents/guardians were aware about enuresis but only
      9.8 % correctly identified it as a health problem. Even though none of the
      children with enuresis ever visited health facility for their problem, a
      statistically significant proportion of the parents desire to discuss with health
      practitioners (p = 0.015). CONCLUSIONS: The proportion of children achieving
      dryness by age 36 months is very small when compared with children from developed
      parts of the world. There is also a high prevalence of enuresis which are not
      reported. Therefore, health workers in the tropics should as a routine enquire
      about enuresis in their daily paediatric care particularly for those children
      from polygamous homes and high social class.

PMID- 21857857
TI  - Outcomes and reasons for dacryocystorhinostomy (DCR) at KCMC, a Tanzanian
      referral hospital, 2001-2006.
AB  - BACKGROUND: External dacryocystorhinostomy (DCR) is a surgical intervention aimed
      to treat blocked nasolacrimal ducts of almost all causes. To date there is only
      limited data available from the Sub Saharan African setting. OBJECTIVES: This
      study aimed to provide further information of the outcomes of DCR in Africa.
      METHODS: Records of all patients undergoing external DCR operations from January
      2001 to April 2006 were systematically searched. 55 patients were identified and
      notes were available for 45 patients. RESULTS: Discharge and epiphora were
      resolved in 90.9% (30/33) and 84.4% (27/32) of patients respectively. Over half
      the cases (51.1%) were children. The commonest reason for operation was chronic
      dacryocystitis (51.1%). Outcomes for DCR were not significantly different for
      either children or adults and a clear improvement of symptoms was found in the
      vast majority of cases. CONCLUSION: This study provides information on the
      outcomes of DCR in the African population. An 84.4% cure rate of epiphora and
      90.9% cure rate of discharge is comparable with findings in other developing
      countries. This study supports the continued use of this intervention in skilled
      hands for treatment of blocked nasolacrimal duct.

PMID- 21857858
TI  - Causes of injuries resulting in a visit to the emergency department of a
      Provincial General Hospital, Nyanza, western Kenya.
AB  - BACKGROUND: There is increasing importance of trauma not only as a major cause of
      surgical admissions, but also a significant cause of morbidity, mortality and
      disability. OBJECTIVE: To document injury-related visits and hospitalization in a
      provincial hospital, western Kenya. METHODS: On-site review of records of all
      patients who visited emergency department (ED) from January 2002 through December
      2003, and admissions of year 2003. RESULTS: A total of 15365 patients visited the
      ED, of which 41% (6319/15395) were injury cases. The leading causes of injury
      were assault (42%), road traffic crashes (RTC) (28%), unspecified soft tissue
      injury (STI) (11%). Cut-wounds, dog-bites, falls, burns and poisoning were
      infrequently reported (each <10%). The age group 15-44 years formed the largest
      proportion (75%). A total of 3253 patients were admitted in 2003, of which 1010
      (31%) were due to injuries. RTC were leading cause of hospitalization (49%)
      followed by assault (16%). Men were more likely to be hospitalized due to assault
      (OR=2.22; CI = 1.45 - 3.41) and not burns or poisoning (p<0.01). There were 64
      (6.3%) injury-related deaths, mainly resulting from RTC (41.9%), burns (19.4%)
      and assault (16.1%). CONCLUSIONS: This study provides considerable information on
      major causes of injuries, useful for epidemiological surveillance and injury
      prevention campaigns.

PMID- 21857859
TI  - Review of the practice of traditional bone setting in Nigeria.
AB  - BACKGROUND: The practice of traditional bone setting (TBS) is extensive in
      Nigeria and it enjoys enormous patronage by the populace. However, the outcome of
      the intervention of TBS treatment is usually poor with profound effects on the
      patient. There are many publications highlighting different aspects of this
      subject but none has summarized the entire practice and problems as a single
      publication. OBJECTIVE: This work aims at reviewing the entire subject of
      traditional bone setting in Nigeria in a single article to enable easy
      understanding and appreciation of the practice and problems of traditional bone
      setting by orthodox practitioners. METHOD: A total of thirty-one relevant
      published original scientific research papers involving all aspects of the
      subject were reviewed and the practices and problems were documented. RESULTS:
      The results showed that the origin of the practice is shrouded in mystery but
      passed on by practitioners from one generation to another. There is no formal
      training of bonesetters. Though the methods of treatment vary, the problems
      caused by them are usually similar with extremity gangrene being the worst. When
      attempts have been made to train the bone setters, improvement have been noted in
      their performance. CONCLUSION: In other to prevent some of the most debilitating
      outcomes like amputation, it is suggested that the TBS practitioners undergo some
      training from orthopaedic practitioners.

PMID- 21857860
TI  - Factors affecting quality of life in cancer patients undergoing chemotherapy.
AB  - BACKGROUND: Cancer can produce many different symptoms, some subtle and some not
      at all subtle. An increasingly important issue in oncology is to evaluate quality
      of life (QoL) in cancer patients. The cancer-specific QoL is related to all
      stages of this disease. OBJECTIVE: The aim of this study was to evaluate the QoL
      in cancer patients with solid tumors and at the different chemotherapy cycles
      (CT). METHODS: This was a cross-sectional study. A total of 200 cancer patients
      were included. With some modification, the European Organization for Research and
      Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30) was used to measure QoL in
      the patients. The QoL in most subjects (66%) was fairly favorable. RESULTS: A
      significant relationship between the cancer type, pain intensity, and fatigue was
      found. However, none of the demographic variables (age, education, marital
      status, income) were significantly related to QoL. Nevertheless, significant
      difference was found between the level of QoL in patients with <= 2 CT cycles
      and/or with 3-5 cycles (p< 0.001). CONCLUSION: Cancer is an important health
      issue influencing QoL. An appropriate treatment which may provide care to the
      cancer patients is CT. A CT cycle may improve QoL in patients with solid tumors.

PMID- 21857861
TI  - Uterine Leiomyomata in South Western Nigeria: a clinical study of presentations
      and management outcome.
AB  - BACKGROUND: Uterine leiomyoma is remarkably common, however only a subset of
      women have their fibroids clinically detected, symptomatic, or warrant surgical
      treatment. Its removal is commonly associated with complications. To prevent or
      control the occurrence of this complication requires the understanding of the
      factors associated with the complications. OBJECTIVE: To evaluate the
      sociodemographic, clinical characteristics, management outcome and its
      determinants in southwestern Nigeria. METHODS: Study was carried out at two large
      tertiary hospitals in the south west region of Nigeria. Retrospective review of
      case records of all surgically managed cases of uterine leiomyoma over a period
      of 25 years. One hundred and fifty nine women with uterine leiomyoma seen and
      managed surgically in South-Western Nigeria were the participants. RESULTS: The
      common presenting complaints were menstrual irregularities (47.7%), abdominal
      swelling (39.1%) and infertility (31.9%). The average uterine size at
      presentation was 15+/-9.7 weeks. The majority (79.9%) of the women presented with
      multiple leiomyomata. The commonest anatomical position of the nodules were
      multiple positions and intramural in 707(60.9%) and 172(14.8%) respectively.
      Myomectomy was performed in 54.7% of cases. Postoperative complications occurred
      in 20.9 % of cases with postoperative pyrexia (13.5%), blood loss warranting
      transfusion (12.8%) and postoperative anaemia (10.4%) been the most common
      complications. CONCLUSION: Uterine fibroid is common in our environment and its
      removal is commonly associated with post-operative pyrexia, blood loss, and
      anaemia and wound infection. Midline incision, closure of rectus sheet with
      chromic catgut and myomectomy were associated with postoperative complications in
      this review.

PMID- 21857863
TI  - Squamous cell carcinoma arising in a mature cystic ovarian teratoma with bladder
      invasion: a case report.
AB  - BACKGROUND: Malignant transformation in a mature cystic ovarian teratoma is rare.
      Except in cases with high index of suspicion or overt metastasis, oophorectomy is
      the mainstay of treatment for ovarian teratoma. METHOD: A 46-year-old
      perimenopausal woman who had salpingo-oophorectomy following a clinical diagnosis
      of benign ovarian tumour that was subsequently reported histologically as mature
      cystic ovarian teratoma with malignant transformation is presented. RESULTS: She
      was referred to our facility based on the histopathology report and haematuria
      two weeks after surgery. Cystoscopic biopsy done was reported as metastatic
      squamous cell carcinoma most probably from the ovary. Patient was thereafter
      referred for radiotherapy but was lost to follow-up after the first course.
      CONCLUSION: Adequate evaluation prior to surgery in suspected ovarian teratoma
      with malignant transformation is critical to determine extent of surgery and
      adjuvant therapy. Prognosis in advanced disease condition such as the case
      presented is generally poor although radical pelvic surgery with resection of the
      adjacent involved bladder before radiotherapy would probably have improved her
      prognosis.

PMID- 21857862
TI  - Metastatic breast cancer in a Nigerian tertiary hospital.
AB  - BACKGROUND: Late presentation of breast carcinoma is common in resource-limited
      countries with attendant poor outcome. OBJECTIVE: To describe the pattern of
      clinical presentation and challenges of treating patients presenting with
      metastatic breast carcinoma in a Nigerian hospital. METHOD: Clinical records of
      all patients who presented with metastatic breast carcinoma between January 1991
      and December 2005 at the Obafemi Awolowo University Teaching Hospitals Complex,
      Ile-Ife, Nigeria were reviewed. RESULTS: More than half of all histologically
      confirmed breast cancer patients seen within the study period presented with
      metastatic disease. Their ages ranged between 20-81 years with a mean age of 45.9
      years. Only 3% (6 of 202) were males. Two-thirds had more than one secondary site
      on initial evaluation and the commonest sites were liver (63%), lung parenchyma
      (51%), pleura (26%) and contralateral breast in 25%. On immunohistochemistry,
      basal like tumours were found in 46.1%. Mastectomy was done in 37 patients with
      fungating breast masses while only one third of those referred to a nearby center
      for radiotherapy had it done. One year survival rate was 27%. CONCLUSION:
      Metastatic disease is common in Nigeria and treatment is limited due to resource
      limitations. Improved awareness of the disease is advocated to reduce late
      presentation.

PMID- 21857864
TI  - Epigastric discomfort during pregnancy presenting as gastric Burkitt lymphoma.

PMID- 21857865
TI  - 5 Year old girl with malignant lymphoblastic lymphoma: challenges of managing
      haematological malignancies in a developing country.
AB  - BACKGROUND: Lymphoblastic lymphoma (LBL) is a neoplasm of lymphoblasts. The
      condition is predominantly lymph node-based disease arising from immature T cells
      in 85-90% of cases and immature B cells in the remainder. The lymphoma is
      aggressive, progresses rapidly, and often presenting as stage IV disease in more
      than 70% of patients. This disease makes up approximately 20% of childhood NHL.
      OBJECTIVE: To show case the management of childhood lymphoblastic lymphoma and
      the handicap faced by the oncologists and pathologists. METHODS: A review of the
      index case was carried out at the paediatric department of Federal Medical
      Centre, Bida, Nigeria. This review took into cognisance patient's demographic bio
      data, case history, general and physical examination, various investigations,
      methods of diagnosis and the type treatment. A comprehensive analysis and account
      of events before and after the commencement of chemotherapy were also reviewed.
      RESULTS: This case identifies a 5 year old girl with aggressive malignant
      lymphoma; lymphoblastic type and the myriad of limitations faced by oncologists
      and pathologists in the management of haematological malignancies. Socio
      cultural, financial (cost implications for the patient for both investigative and
      therapeutic interventions), inadequate resources and facilities were identified
      as some of the constraints leading to inadequate management and poor outcome in
      patients with this condition. CONCLUSION: Given the limitations associated with
      the management of cancers in this part of the world, efforts on the part of
      government and non-governmental agencies are necessary to strengthen and upgrade
      the existing facilities in various hospitals. The social welfare departments of
      tertiary hospitals should be adequately funded to meet the demand of this group
      of patients.

PMID- 21857866
TI  - Papillary thyroid carcinoma presenting as a lateral neck cyst.
AB  - BACKGROUND: Solitary lateral cervical cystic mass is an uncommon presentation of
      papillary thyroid carcinoma. OBJECTIVES: To report our recent experience in the
      diagnosis and management of papillary thyroid carcinoma presenting as a lateral
      neck cyst. METHODS: Patients who had papillary thyroid carcinoma and presented as
      a painless lateral neck cyst at the Department of Surgery, Al-Ain Hospital, from
      April 2005 to June 2009 were retrospectively studied. Their clinical
      presentation, diagnosis and management were reviewed. RESULTS: Five patients were
      studied. No thyroid nodules were clinically palpable in all patients. Fine needle
      aspiration cytology from the cyst was positive for papillary thyroid carcinoma in
      three patients (60 percent). Two patients were diagnosed after excisional biopsy.
      Three patients had total thyroidectomy with modified radical neck dissection and
      postoperative radioactive iodine ablation. Two patients preferred to travel
      overseas for treatment. Thyroid histopathological examination has shown papillary
      thyroid carcinoma in all operated patients with multiple microscopic foci in two
      of them. This was associated with multiple bilateral cervical lymph node
      involvement. CONCLUSIONS: Metastatic papillary thyroid carcinoma presenting as a
      neck cyst is a diagnostic challenge. Excisional biopsy is indicated if fine
      needle aspiration cytology was inconclusive so as to rule out malignancy.

PMID- 21857867
TI  - Capacity building for assessing new technologies: approaches to examining
      personalized medicine in practice.
AB  - This article focuses on the overarching question: how can we use existing data to
      develop the capacity to improve the evidence base on personalized medicine
      technologies and particularly regarding their utilization and clinical utility?
      We focus on data from health payers who are key stakeholders in capacity
      building, as they need data to guide decisions and they develop data as part of
      operations. Broadly defined, health payers include insurance carriers, third
      party payers, health-plan sponsors and organized delivery systems. Data from
      health payers have not yet been widely used to assess personalized medicine. Now,
      with an increasing number of personalized technologies covered and reimbursed by
      health payers, and an increasing number of emerging technologies that will
      require policy decisions, there is a great opportunity to develop the evidence
      base using payer data and by engaging with these stakeholders. Here, we describe
      data that are available from, and are being developed by, health payers and
      assess how these data can be further developed to increase the capacity for
      future research, using three examples. The examples suggest that payer data can
      be used to examine clinical utility and approaches can be developed that
      simultaneously address the characteristics of personalized medicine, real world
      data and organizations. These examples can now help us to elucidate how to best
      examine clinical utility in actual practice and build evaluation approaches that
      can be applied to future technologies.

PMID- 21857869
TI  - Finding a way out: Why developmental science does not need another "ism"
AB  - Neoconstructivism is a new approach in developmental science that sheds light on
      the processes underlying change over time. The present commentary evaluates this
      new approach in the context of existing theories of development and nine central
      tenets of neoconstructivism proposed by Newcombe (2011). For inspiration, Hull's
      evaluation of psychological theory in 1935 is discussed. Hull noted a
      proliferation of theories that he attributed to poorly specified concepts and a
      lack of rigorous theoretical work. Noting a similar proliferation of "isms" in
      developmental science, the commentary concludes that existing theories have much
      to offer and suggests that what is needed is not a new "ism" but a rigorous
      evaluation and integration of modern developmental concepts.

PMID- 21857868
TI  - Progesterone receptor action: defining a role in breast cancer.
AB  - The ovarian steroid hormones, estradiol and progesterone, and their nuclear
      receptors (estrogen receptor [ER] and progesterone receptor [PR]), are involved
      in breast cancer development. As ER-positive/PR-positive tumors progress, they
      are likely to become steroid hormone-resistant/independent, yet often retain
      expression of their steroid receptors. Notably, up to 40% of women with steroid
      receptor-positive tumors exhibit de novo resistance or eventually fail on
      estrogen- or ERalpha-blocking therapies (acquired resistance). Indeed, most of
      the research on this topic has centered on mechanisms of ER 'escape' from
      endocrine therapy and the design of better ER-blocking strategies; signaling
      pathways that mediate endocrine (i.e., anti-estrogen) resistance are also
      excellent therapeutic targets. However, serious consideration of PR isoforms as
      important drivers of early breast cancer progression and ER modulators is timely
      and significant. Indeed, progress has been hindered by ER-centric experimental
      approaches. This article will focus on defining a role for PR in breast cancer
      with hopes of providing a refreshing PR-focused perspective.

PMID- 21857870
TI  - FPGA acceleration of rigid-molecule docking codes.
AB  - Modelling the interactions of biological molecules, or docking, is critical both
      to understanding basic life processes and to designing new drugs. The field
      programmable gate array (FPGA) based acceleration of a recently developed,
      complex, production docking code is described. The authors found that it is
      necessary to extend their previous three-dimensional (3D) correlation structure
      in several ways, most significantly to support simultaneous computation of
      several correlation functions. The result for small-molecule docking is a 100
      fold speed-up of a section of the code that represents over 95% of the original
      run-time. An additional 2% is accelerated through a previously described method,
      yielding a total acceleration of 36* over a single core and 10* over a quad-core.
      This approach is found to be an ideal complement to graphics processing unit
      (GPU) based docking, which excels in the protein-protein domain.

PMID- 21857871
TI  - Spinal cord compression: to biopsy, or not to biopsy?
AB  - A patient presenting with acute spinal cord compression initially thought to be
      secondary to metastatic cancer based on magnetic resonance imaging alone is
      described. No primary tumour was identified on further imaging, and although
      deemed to be technically very difficult, surgical decompression was postponed in
      favour of obtaining a histological diagnosis. Histology confirmed a low grade non
      Hodgkin's lymphoma, a diagnosis which would not have been considered had a biopsy
      not been undertaken. The correct curative treatment was subsequently initiated,
      and the patient responded well to localised radiotherapy and intrathecal
      methotrexate.

PMID- 21857872
TI  - Management of recurrent pacemaker-related bacteraemia with small colony variant
      Staphylococcus aureus in a haemodialysis patient.
AB  - A patient with chronic haemodialysis with a cardiac pacemaker was admitted for
      five episodes of bacteraemia with Staphylococcus during an 8-month period. The
      species identification was complicated since the morphological characters and
      biochemical reactions were unusual and differing. Molecular biological
      identification and typing methods revealed that the pathogens for all the
      episodes were the same strain of Staphylococcus aureus that had small colony
      variant characteristics. Continuous suppressive antibiotic treatment initiated
      after the last infection episode has been able to keep the patient free of
      bacteraemia relapse during the past 24 months without removing the pacemaker.

PMID- 21857873
TI  - Is drug-resistant Salmonella typhi an emerging threat?
AB  - Enteric fever is a common cause of morbidity and mortality worldwide and more so
      in a developing country like India. Worldwide, the incidence of multidrug
      Salmonella typhi is increasing alarmingly. Similarly, a multiplicity of factors
      affects the in vivo susceptibility of a microorganism. We report a case of
      multidrug resistant complicated enteric fever with resistance to ceftriaxone and
      azithromycin.

PMID- 21857874
TI  - Endoscopic management of inverted papilloma of the sphenoid sinus.
AB  - We present the case of a rare sinonasal tumour originating in a rare location in
      close proximity to vital structures. We describe how the patient was managed,
      including detailed description of how the mass was removed.A 54-year-old man
      presented with a long history of nasal blockage, recently complicated by severe
      headaches and a left VIth nerve palsy. CT scan showed complete opacification of
      the left sphenoid sinus.Symptoms improved following administration of steroids
      and nasal decongestants. Histology from endoscopic debulking of the mass
      confirmed the presence of inverted papilloma. Fine-cut CT showed the course of
      the carotid artery and optic nerve, closely related to the tumour, allowing for
      complete removal during a second endoscopic procedure. Five years following the
      procedure, the patient remains symptom free.With appropriate imaging, isolated
      sphenoid sinus tumours can be removed endoscopically even when in close relation
      to vital structures.

PMID- 21857875
TI  - Traumatic pancreatic injury during playing sports.
AB  - The patient was a 33-year-old man. He had severe upper abdominal pain after a
      rugby game and he was diagnosed with traumatic pancreatic injury. Since intra
      abdominal bleeding became severe, laparotomy was performed for haemostasis. On
      operation, venous bleeding from the upper edge of the head of the pancreas was
      found and the haemorrhage was stopped. The whole pancreas had severe inflammation
      with oedematous tissue spreading into the meso-colon and meso-jejunum. On the
      same day, the patient was transferred to our hospital for further treatment of
      acute pancreatitis. On admission, the amylase level in the drainage fluid was
      high and, thus, we started continuous arterial infusion treatment via the
      superior mesenteric artery, in addition to subcutaneous administration of
      octreotide. Enteral nutrition was started on postoperative day 6, oral intake was
      started on postoperative day 15. The patient recovered successfully and was
      discharged on postoperative day 30.

PMID- 21857876
TI  - Schistosomiasis-induced male infertility.
AB  - Azoospermia is a rare, irreversible complication in the UK resulting from heavy
      infection of schistosomiasis of the male genital tract. Adequate anti-bilharzial
      treatment and close follow-up with urological assessments should reduce the risk
      of chronic ill health. This patient contracted schistosomiasis following swimming
      in lakes in Uganda, Africa, which resulted in azoospermia and reversible loss of
      libido. The couple underwent treatment at our assisted conception programme with
      testicular sperm extraction and intracytoplasmic sperm injection (ICSI). The
      female partner conceived in her second stimulated ICSI cycle and had a
      spontaneous vaginal delivery at term.

PMID- 21857877
TI  - Acute coronary thrombosis in a patient with septic shock without any evidence of
      disseminated intravascular coagulation.
AB  - The case report describes an interesting and unusual finding of acute coronary
      artery thrombosis in a patient presenting with septic shock without any clinical
      and laboratory evidence of disseminated intravascular coagulation (DIC). The
      patient presented with leucocytosis and refractory hypotension requiring pressor
      support and found to have anterior and inferior ST-elevation in 12-lead
      electrocardiogram. Coronary angiogram revealed acute thrombotic occlusions in the
      proximal right coronary artery and the proximal left anterior descending coronary
      artery. There was no occlusive atherosclerotic coronary artery disease. The
      patient underwent mechanical thrombectomy. Haemodynamic parameters obtained from
      right heart catheterisation confirmed sepsis as the aetiology of hypotension. The
      patient was treated successfully with broad spectrum antibiotics, pressors and
      intravenous fluid.Acute myocardial infarctions as a complication secondary to
      disseminated intravascular coagulation in patients with sepsis and septic shock
      have been described in the literature. To our knowledge, this is the first
      reported case of acute coronary artery thrombosis in patient with septic shock
      without DIC and without any underlying occlusive coronary artery disease.

PMID- 21857878
TI  - Obstructive jaundice as a presenting symptom of metastatic carcinoma of the
      prostate.
AB  - Liver dysfunction is not an uncommon association with malignancy. However,
      obstructive jaundice as the first clinical presentation of metastatic carcinoma
      of the prostate is rare with only a few such cases reported in the literature.
      The aetiology of obstructive jaundice in these cases can be due to direct
      invasion of the tumour or external compression of the biliary tree or, rarely,
      related to a paraneoplastic phenomenon. Here, we report a case of obstructive
      jaundice being the presenting symptom of metastatic carcinoma of the prostate
      secondary to lymph node obstruction and review the literature.

PMID- 21857879
TI  - Chronic inflammatory demyelinating polyneuropathy in a patient infected with
      human T lymphotropic virus type I.
AB  - A 32-year-old Afro-Caribbean woman presented with a 1-year history of slowly
      progressive sensory and motor symptoms initially affecting the legs and later
      involving the arms. Clinical examination demonstrated a mainly distal pattern of
      weakness with little objective sensory impairment. The clinical features
      suggested the possibility of chronic inflammatory demyelinating polyneuropathy.
      This diagnosis was supported by neurophysiological testing and examination of the
      cerebrospinal fluid and confirmed by sural nerve biopsy as well as by exclusion
      of other causes of neuropathy. Seropositivity for human T lymphotropic virus type
      I (HTLV-I) was demonstrated. The clinical significance of this finding in an area
      with a high HTLV-I endemicity, as well as its possible aetiological relevance to
      the diagnosis of chronic inflammatory demyelinating polyneuropathy, is discussed.

PMID- 21857880
TI  - Bipartite atlas mimicking traumatic atlantoaxial instability following a rugby
      tackle.
AB  - We report a very rare case of a congenital cervical spine anomaly. The low
      occurrence rate of this anatomic variant combined with the high frequency of
      cervical injuries in sports medicine made this case a diagnostic challenge on
      both emergency and orthopaedic departments. After reading, it should give the
      clinician a more consistent view in differentiating the traumatic or congenital
      origin of the disorder seen on radiographs, as well as what can be expected in
      the future when diagnosis is set.

PMID- 21857881
TI  - Skier's toe: traumatic onycholysis complicated by Pseudomonas chloronychia.

PMID- 21857882
TI  - Helicobacter pylori Infection and Gastric Adenocarcinoma.
AB  - Gastric adenocarcinoma is the second leading cause of cancer-related mortality
      worldwide. Infection with Helicobacter pylori is the strongest recognized risk
      factor for gastric adenocarcinoma. This bacterial species colonizes the stomach
      of more than half of the world's population; however, only a very small
      proportion of infected subjects develop adenocarcinoma. H. pylori causes a
      chronic gastritis that may last decades, and a multistep precancerous process is
      recognized for the most frequent histologic type of gastric adenocarcinoma: the
      intestinal type. The severity and long-term outcome of this infection is
      modulated by an increasing list of bacterial, host, and environmental factors,
      which interplay in a complex manner. Identification of individuals at high risk
      for gastric cancer that may enter a surveillance program and intervention during
      the precancerous process is the most suitable strategy for decreasing mortality
      due to this malignancy.

PMID- 21857883
TI  - The metabolic syndrome, hypertriglyceridemic waist, and cardiometabolic risk
      factor profile in obese women.
AB  - The hypertriglyceridemic waist (HTGW) and metabolic syndrome (MS) are associated
      with increased cardiometabolic risk. We evaluated the impact of the HTGW on
      cardiometabolic risk factors in obese women diagnosed with the MS. Thirty-six
      abdominally obese women with the MS as defined by the International Diabetes
      Federation (IDF) [(mean (SD); age 49 (11) y, ht 165 (6) cm, wt 95 (16) kg]
      participated. The HTGW was defined as follows: a waist circumference >=80 cm and
      triglycerides >=1.7 mM. Unpaired t-tests and Analysis of Covariance (ANCOVA) were
      employed to detect mean differences between women with MS plus or minus HTGW.
      Women with the MS plus HTGW had higher total cholesterol (16%, p=0.015), VLDL
      cholesterol (97%, p<0.001), non-HDL-cholesterol (16%, p=0.002), insulin (40%,
      p=0.043), and abdominal visceral fat (24%, p=0.100), and lower total HDL
      cholesterol (6%, p=0.024), HDL(3) (11%, p=0.031) and Quantitative Insulin
      Sensitivity Check Index (QUICKI) (5%, p=0.068) compared with women with the MS
      minus HTGW. Thus, the presence of the HTGW was accompanied by a worsened
      cardiometabolic risk factor profile in these obese women with the MS. In
      particular, women with the MS plus HTGW were more insulin resistant compared to
      women with the MS minus HTGW. In conclusion, the presence of the HTGW in obese
      women with the MS exacerbates insulin resistance and cardiometabolic risk
      factors.

PMID- 21857884
TI  - Live Cell Imaging of Src/FAK Signaling by FRET.
AB  - The Src/FAK complex is involved in many signaling pathways and plays crucial
      roles in cell adhesion/migration. It becomes clear that the subcellular
      localization of Src and FAK is crucial for their activities and functions. In
      this article, we first overview the molecular mechanisms and functions of Src and
      FAK involved in cell adhesion/migration. We then introduce the development of
      genetically encoded biosensors based on fluorescence resonance energy transfer
      (FRET) to visualize the activities of Src and FAK in live cells with high
      spatiotemporal resolutions. Different kinds of signal peptides targeting
      subcellular compartments are also discussed. FRET-based biosensors fused with
      these targeting signals peptides are further introduced to provide an overview on
      how these targeting signals can facilitate the localization of biosensors to
      continuously monitor the local activity of Src and FAK at subcellular
      compartments. In summary, genetically-encoded FRET biosensors integrated with
      subcellular compartment-targeting signals can provide powerful tools for the
      visualization of subcellular Src and FAK activities in live cells and advance our
      in-depth understanding of Src/FAK functions at different subcellular
      compartments.

PMID- 21857886
TI  - Trends in Labor Force Participation: How Much is Due to Changes in Pensions?
AB  - In the United States, beginning in the late 1980s there was a substantial
      increase in the labor force participation of men and women in their 60s. Over the
      same time period the type of pension plans offered by employers shifted strongly
      from defined benefit plans to defined contribution plans. Defined benefit plans
      typically have optimal retirement ages embedded in their structure which induce
      early retirement, whereas defined contribution plans do not favor any particular
      retirement age. Based on panel data, this paper quantifies the increase in
      participation due to the change in pension structure. The main result is that the
      pension changes account for a considerable part of the increase, but other
      factors also made a contribution.

PMID- 21857885
TI  - The Biology of TRAIL and the Role of TRAIL-Based Therapeutics in Infectious
      Diseases.
AB  - TNF-related apoptosis inducing ligand (TRAIL) is a key mediator of the innate
      immune response to infection. While TRAIL-mediated apoptosis plays an essential
      role in the clearance of virus-infected cells, its physiologic role also includes
      immunosurveilance for cancer cells. Therapeutics that induce TRAIL-mediated
      apoptosis in cancer cells remain a focus of ongoing investigation in clinical
      trials, and much has been learned from these studies regarding the efficacy and
      toxicity of these interventions. These data, combined with data from numerous
      preclinical studies that detail the important and multifaceted role of TRAIL
      during infection with human immunodeficiency virus and other viruses, suggest
      that therapeutic exploitation of TRAIL signaling offers a novel and efficacious
      strategy for the management of infectious diseases.

PMID- 21857887
TI  - Impact of Radiotherapy Dose on Dentition Breakdown in Head and Neck Cancer
      Patients.
AB  - PURPOSE: To evaluate the severity of post-radiation dental lesions and possible
      correlation with radiation dose to the teeth in patients treated for head and
      neck cancers. METHODS AND MATERIALS: Data from 93 head and neck radiotherapy
      patients treated between 1997 and 2008 were analyzed retrospectively. The main
      effect, radiation dose to the individual teeth, was evaluated with covariates of
      elapsed time after radiation, xerostomia, topical fluoride use, and oral hygiene
      status included. Patients' radiotherapy plans were used to calculate cumulative
      exposure for each tooth. Patients' teeth were evaluated using a validated index
      and then categorized as having none/slight or moderate/severe post-radiation
      damage. RESULTS: Patients (31 females, 62 males) ranged in age from 18-82 yrs
      (mean=57). The number of teeth/patient ranged from 3-30 (mean=20) with a total of
      1873 teeth evaluated. Overall, 51% of teeth had moderate/severe damage, with the
      remaining having little or none. Using odds ratios and 95% confidence intervals,
      the odds for moderate/severe damage were 2-3x greater for teeth exposed to
      between 30-60 Gy as compared to no radiation. However, for teeth exposed to >=60
      Gy as compared to no radiation the odds of moderate/severe tooth damage was
      greater by a magnitude of 10 times. CONCLUSIONS: The results indicate that there
      is minimal tooth damage below 30 Gy (salivary gland threshold), a greater than
      1:1 increased dose-response between 30-60y likely related to salivary gland
      damage, and a critical threshold of >=60Gy which may be linked to direct effects
      of radiation on tooth structure. These findings suggest that care should be taken
      during the treatment planning process to limit tooth dose, and when clinically
      possible to limit tooth dose to less than 60 Gy.

PMID- 21857888
TI  - Multiple-Antenna Microwave Ablation: Spatially Distributing Power Improves
      Thermal Profiles and Reduces Invasiveness.
AB  - BACKGROUND: Microwave ablation is an emerging tumor ablation modality. To date,
      microwave systems have generally utilized single large-diameter antennas to
      deliver high input powers.  OBJECTIVE: To determine whether spatially
      distributing power through an array of multiple smaller antennas creates a more
      uniform thermal profile and increases peripheral tissue temperatures when
      compared with microwave ablation using a single larger antenna.  METHODS:
      Microwave ablations were performed in ex vivo bovine liver using a single 2.45
      GHz magnetron generator and a constant total input power (90 W) delivered through
      either a single 13-gauge antenna, two 17-gauge antennas, or three 18-gauge
      antennas. Multiple antennas were driven coherently. Temperatures were recorded at
      5-mm radial distances and the resulting thermal profiles and ablation zones were
      compared using analysis of variance.  RESULTS: Multiple-antenna configurations
      were less invasive (ie, the area of tissue punctured was smaller) than the single
      antenna configuration; despite this, ablation zones created using multiple
      smaller antennas were larger and as circular when compared with those created
      using a single larger antenna. Multiple-antenna configurations resulted in more
      uniform thermal profiles and higher peripheral tissue temperatures.  CONCLUSION:
      Distributing power evenly among multiple smaller antennas resulted in larger
      ablation zones with more uniform thermal profiles than more invasive ablations
      with a larger single antenna.

PMID- 21857889
TI  - ANALYSIS OF ROLLING GROUP THERAPY DATA USING CONDITIONALLY AUTOREGRESSIVE PRIORS.
AB  - Group therapy is a central treatment modality for behavioral health disorders
      such as alcohol and other drug use (AOD) and depression. Group therapy is often
      delivered under a rolling (or open) admissions policy, where new clients are
      continuously enrolled into a group as space permits. Rolling admissions policies
      result in a complex correlation structure among client outcomes. Despite the
      ubiquity of rolling admissions in practice, little guidance on the analysis of
      such data is available. We discuss the limitations of previously proposed
      approaches in the context of a study that delivered group cognitive behavioral
      therapy for depression to clients in residential substance abuse treatment. We
      improve upon previous rolling group analytic approaches by fully modeling the
      interrelatedness of client depressive symptom scores using a hierarchical
      Bayesian model that assumes a conditionally autoregressive prior for session
      level random effects. We demonstrate improved performance using our method for
      estimating the variance of model parameters and the enhanced ability to learn
      about the complex correlation structure among participants in rolling therapy
      groups. Our approach broadly applies to any group therapy setting where groups
      have changing client composition. It will lead to more efficient analyses of
      client-level data and improve the group therapy research community's ability to
      understand how the dynamics of rolling groups lead to client outcomes.

PMID- 21857890
TI  - Influence of urbanization on demography of little brown bats (Myotis lucifugus)
      in the prairies of North America.
AB  - BACKGROUND: We address three key gaps in research on urban wildlife ecology:
      insufficient attention to (1) grassland biomes, (2) individual- and population
      level effects, and (3) vertebrates other than birds. We hypothesized that
      urbanization in the North American Prairies, by increasing habitat complexity
      (via the proliferation of vertical structures such as trees and buildings),
      thereby enhancing the availability of day-roosts, tree cover, and insects, would
      benefit synanthropic bats, resulting in increased fitness among urban
      individuals. METHODOLOGY/PRINCIPAL FINDINGS: Over three years, we captured more
      than 1,600 little brown bats (Myotis lucifugus) in urban and non-urban riparian
      sites in and around Calgary, Alberta, Canada. This species dominated bat
      assemblages throughout our study area, but nowhere more so than in the city. Our
      data did not support most of our specific predictions. Increased numbers of urban
      bats did not reflect urbanization-related benefits such as enhanced body
      condition, reproductive rates, or successful production of juveniles. Instead,
      bats did best in the transition zone situated between strictly urban and rural
      areas. CONCLUSIONS/SIGNIFICANCE: We reject our hypothesis and explore various
      explanations. One possibility is that urban and rural M. lucifugus exhibit
      increased use of anthropogenic roosts, as opposed to natural ones, leading to
      larger maternity colonies and higher population densities and, in turn, increased
      competition for insect prey. Other possibilities include increased stress,
      disease transmission and/or impacts of noise on urban bats. Whatever the
      proximate cause, the combination of greater bat population density with decreased
      body condition and production of juveniles indicates that Calgary does not
      represent a population source for Prairie bats. We studied a highly synanthropic
      species in a system where it could reasonably be expected to respond positively
      to urbanization, but failed to observe any apparent benefits at the individual
      level, leading us to propose that urban development may be universally
      detrimental to bats.

PMID- 21857891
TI  - Emergence of scale-free leadership structure in social recommender systems.
AB  - The study of the organization of social networks is important for the
      understanding of opinion formation, rumor spreading, and the emergence of trends
      and fashion. This paper reports empirical analysis of networks extracted from
      four leading sites with social functionality (Delicious, Flickr, Twitter and
      YouTube) and shows that they all display a scale-free leadership structure. To
      reproduce this feature, we propose an adaptive network model driven by social
      recommending. Artificial agent-based simulations of this model highlight a "good
      get richer" mechanism where users with broad interests and good judgments are
      likely to become popular leaders for the others. Simulations also indicate that
      the studied social recommendation mechanism can gradually improve the user
      experience by adapting to tastes of its users. Finally we outline implications
      for real online resource-sharing systems.

PMID- 21857893
TI  - A secular trend toward earlier male sexual maturity: evidence from shifting ages
      of male young adult mortality.
AB  - This paper shows new evidence of a steady long-term decline in age of male sexual
      maturity since at least the mid-eighteenth century. A method for measuring the
      timing of male maturity is developed based on the age at which male young adult
      mortality accelerates. The method is applied to mortality data from Sweden,
      Denmark, Norway, the United Kingdom, and Italy. The secular trend toward earlier
      male sexual maturity parallels the trend toward earlier menarche for females,
      suggesting that common environmental cues influence the speed of both males' and
      females' sexual maturation.

PMID- 21857894
TI  - Joining inventory by parataxonomists with DNA barcoding of a large complex
      tropical conserved wildland in northwestern Costa Rica.
AB  - BACKGROUND: The many components of conservation through biodiversity development
      of a large complex tropical wildland, Area de Conservacion Guanacaste (ACG),
      thrive on knowing what is its biodiversity and natural history. For 32 years a
      growing team of Costa Rican parataxonomists has conducted biodiversity inventory
      of ACG caterpillars, their food plants, and their parasitoids. In 2003, DNA
      barcoding was added to the inventory process. METHODOLOGY/PRINCIPAL FINDINGS: We
      describe some of the salient consequences for the parataxonomists of barcoding
      becoming part of a field biodiversity inventory process that has centuries of
      tradition. From the barcoding results, the parataxonomists, as well as other
      downstream users, gain a more fine-scale and greater understanding of the
      specimens they find, rear, photograph, database and deliver. The parataxonomists
      also need to adjust to collecting more specimens of what appear to be the "same
      species"--cryptic species that cannot be distinguished by eye or even food plant
      alone--while having to work with the name changes and taxonomic uncertainty that
      comes with discovering that what looked like one species may be many.
      CONCLUSIONS/SIGNIFICANCE: These career parataxonomists, despite their lack of
      formal higher education, have proven very capable of absorbing and working around
      the additional complexity and requirements for accuracy and detail that are
      generated by adding barcoding to the field base of the ACG inventory. In the
      process, they have also gained a greater understanding of the fine details of
      phylogeny, relatedness, evolution, and species-packing in their own tropical
      complex ecosytems. There is no reason to view DNA barcoding as incompatible in
      any way with tropical biodiversity inventory as conducted by parataxonomists.
      Their year-round on-site inventory effort lends itself well to the sampling
      patterns and sample sizes needed to build a thorough barcode library.
      Furthermore, the biological understanding that comes with barcoding increases the
      scientific penetrance of biodiversity information, DNA understanding, evolution,
      and ecology into the communities in which the parataxonomists and their families
      are resident.

PMID- 21857895
TI  - Reading the complex skipper butterfly fauna of one tropical place.
AB  - BACKGROUND: An intense, 30-year, ongoing biodiversity inventory of Lepidoptera,
      together with their food plants and parasitoids, is centered on the rearing of
      wild-caught caterpillars in the 120,000 terrestrial hectares of dry, rain, and
      cloud forest of Area de Conservacion Guanacaste (ACG) in northwestern Costa Rica.
      Since 2003, DNA barcoding of all species has aided their identification and
      discovery. We summarize the process and results for a large set of the species of
      two speciose subfamilies of ACG skipper butterflies (Hesperiidae) and emphasize
      the effectiveness of barcoding these species (which are often difficult and time
      consuming to identify). METHODOLOGY/PRINCIPAL FINDINGS: Adults are DNA barcoded
      by the Biodiversity Institute of Ontario, Guelph, Canada; and they are identified
      by correlating the resulting COI barcode information with more traditional
      information such as food plant, facies, genitalia, microlocation within ACG,
      caterpillar traits, etc. This process has found about 303 morphologically defined
      species of eudamine and pyrgine Hesperiidae breeding in ACG (about 25% of the ACG
      butterfly fauna) and another 44 units indicated by distinct barcodes (n = 9,094),
      which may be additional species and therefore may represent as much as a 13%
      increase. All but the members of one complex can be identified by their DNA
      barcodes. CONCLUSIONS/SIGNIFICANCE: Addition of DNA barcoding to the methodology
      greatly improved the inventory, both through faster (hence cheaper) accurate
      identification of the species that are distinguishable without barcoding, as well
      as those that require it, and through the revelation of species "hidden" within
      what have long been viewed as single species. Barcoding increased the recognition
      of species-level specialization. It would be no more appropriate to ignore
      barcode data in a species inventory than it would be to ignore adult genitalia
      variation or caterpillar ecology.

PMID- 21857896
TI  - Electrical activation in the coronary sinus branches as a guide to cardiac
      resynchronisation therapy: rationale for a coordinate system.
AB  - BACKGROUND: For successful cardiac resynchronisation therapy (CRT) a spatial and
      electrical separation of right and left ventricular electrodes is essential. The
      spatial distribution of electrical delays within the coronary sinus (CS)
      tributaries has not yet been identified. OBJECTIVE: Electrical delays within the
      CS are described during sinus rhythm (SR) and right ventricular pacing (RVP). A
      coordinate system grading the mitral ring from 0 degrees  to 360 degrees  and
      three vertical segments is proposed to define the lead positions irrespective of
      individual CS branch orientation. METHODS: In 13 patients undergoing implantation
      of a CRT device 6+/-2.5, (median 5) lead positions within the CS were mapped
      during SR and RVP. The delay to the onset and the peak of the local signal was
      measured from the earliest QRS activation or the pacing spike. Fluoroscopic
      positions were compared to localizations on a nonfluoroscopic electrode imaging
      system. RESULTS: During SR, electrical delays in the CS were inhomogenous in
      patients with or without left bundle branch block (LBBB). During RVP, the delays
      increased by 44+/-32 ms (signal onset from 36+/-33 ms to 95+/-30 ms; p<0.001,
      signal peak from 105+/-44 ms to 156+/-30 ms; p<0.001). The activation pattern
      during RVP was homogeneous and predictable by taking the grading on the CS ring
      into account: (% QRS) = 78-0.002 (grade-162)(2), p<0.0001. This indicates that
      78% of the QRS duration can be expected as a maximum peak delay at 162 degrees 
      on the CS ring. CONCLUSION: Electrical delays within the CS vary during SR, but
      prolong and become predictable during RVP. A coordinate system helps predicting
      the local delays and facilitates interindividual comparison of lead positions
      irrespective of CS branch anatomy.

PMID- 21857897
TI  - DNA barcode sequence identification incorporating taxonomic hierarchy and within
      taxon variability.
AB  - For DNA barcoding to succeed as a scientific endeavor an accurate and expeditious
      query sequence identification method is needed. Although a global multiple
      sequence alignment can be generated for some barcoding markers (e.g. COI, rbcL),
      not all barcoding markers are as structurally conserved (e.g. matK). Thus,
      algorithms that depend on global multiple-sequence alignments are not universally
      applicable. Some sequence identification methods that use local pairwise
      alignments (e.g. BLAST) are unable to accurately differentiate between highly
      similar sequences and are not designed to cope with hierarchic phylogenetic
      relationships or within taxon variability. Here, I present a novel alignment-free
      sequence identification algorithm--BRONX--that accounts for observed within taxon
      variability and hierarchic relationships among taxa. BRONX identifies short
      variable segments and corresponding invariant flanking regions in reference
      sequences. These flanking regions are used to score variable regions in the query
      sequence without the production of a global multiple-sequence alignment. By
      incorporating observed within taxon variability into the scoring procedure,
      misidentifications arising from shared alleles/haplotypes are minimized. An
      explicit treatment of more inclusive terminals allows for separate
      identifications to be made for each taxonomic level and/or for user-defined
      terminals. BRONX performs better than all other methods when there is imperfect
      overlap between query and reference sequences (e.g. mini-barcode queries against
      a full-length barcode database). BRONX consistently produced better
      identifications at the genus-level for all query types.

PMID- 21857898
TI  - Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the
      permeability of blood-brain barrier by disrupting tight junction proteins.
AB  - Central nervous system (CNS) involvement remains an important cause of morbidity
      and mortality in acute leukemia, the mechanisms of leukemic cell infiltration
      into the CNS have not yet been elucidated. The blood-brain barrier (BBB) makes
      CNS become a refugee to leukemic cells and serves as a resource of cells that
      seed extraneural sites. How can the leukemic cells disrupt this barrier and
      invasive the CNS, even if many of the currently available chemotherapies can not
      cross the BBB? Tight junction in endothelial cells occupies a central role in the
      function of the BBB. Except the well known role of degrading extracellular matrix
      in metastasis of cancer cells, here we show matrix metalloproteinase (MMP)-2 and 
      9, secreted by leukemic cells, mediate the BBB opening by disrupting tight
      junction proteins in the CNS leukemia. We demonstrated that leukemic cells
      impaired tight junction proteins ZO-1, claudin-5 and occludin resulting in
      increased permeability of the BBB. However, these alterations reduced when MMP-2
      and -9 activities were inhibited by RNA interference strategy or by MMP inhibitor
      GM6001 in an in vitro BBB model. We also found that the disruption of the BBB in
      company with the down-regulation of ZO-1, claudin-5 and occludin and the up
      regulation of MMP-2 and -9 in mouse brain tissues with leukemic cell infiltration
      by confocal imaging and the assay of in situ gelatin zymography. Besides, GM6001
      protected all mice against CNS leukemia. Our findings suggest that the
      degradation of tight junction proteins ZO-1, claudin-5 and occludin by MMP-2 and 
      9 secreted by leukemic cells constitutes an important mechanism in the BBB
      breakdown which contributes to the invasion of leukemic cells to the CNS in acute
      leukemia.

PMID- 21857899
TI  - Integrated mapping of establishment risk for emerging vector-borne infections: a
      case study of canine leishmaniasis in southwest France.
AB  - BACKGROUND: Zoonotic visceral leishmaniasis is endemic in the Mediterranean
      Basin, where the dog is the main reservoir host. The disease's causative agent,
      Leishmania infantum, is transmitted by blood-feeding female sandflies. This paper
      reports an integrative study of canine leishmaniasis in a region of France
      spanning the southwest Massif Central and the northeast Pyrenees, where the
      vectors are the sandflies Phlebotomus ariasi and P. perniciosus. METHODS:
      Sandflies were sampled in 2005 using sticky traps placed uniformly over an area
      of approximately 100 by 150 km. High- and low-resolution satellite data for the
      area were combined to construct a model of the sandfly data, which was then used
      to predict sandfly abundance throughout the area on a pixel by pixel basis
      (resolution of c. 1 km). Using literature- and expert-derived estimates of other
      variables and parameters, a spatially explicit R(0) map for leishmaniasis was
      constructed within a Geographical Information System. R(0) is a measure of the
      risk of establishment of a disease in an area, and it also correlates with the
      amount of control needed to stop transmission. CONCLUSIONS: To our knowledge,
      this is the first analysis that combines a vector abundance prediction model,
      based on remotely-sensed variables measured at different levels of spatial
      resolution, with a fully mechanistic process-based temperature-dependent R(0)
      model. The resulting maps should be considered as proofs-of-principle rather than
      as ready-to-use risk maps, since validation is currently not possible. The
      described approach, based on integrating several modeling methods, provides a
      useful new set of tools for the study of the risk of outbreaks of vector-borne
      diseases.

PMID- 21857900
TI  - Population genetics of an ecosystem-defining reef coral Pocillopora damicornis in
      the Tropical Eastern Pacific.
AB  - BACKGROUND: Coral reefs in the Tropical Eastern Pacific (TEP) are amongst the
      most peripheral and geographically isolated in the world. This isolation has
      shaped the biology of TEP organisms and lead to the formation of numerous endemic
      species. For example, the coral Pocillopora damicornis is a minor reef-builder
      elsewhere in the Indo-West Pacific, but is the dominant reef-building coral in
      the TEP, where it forms large, mono-specific stands, covering many hectares of
      reef. Moreover, TEP P. damicornis reproduces by broadcast spawning, while it
      broods mostly parthenogenetic larvae throughout the rest of the Indo-West
      Pacific. Population genetic surveys for P. damicornis from across its Indo
      Pacific range indicate that gene flow (i.e. larval dispersal) is generally
      limited over hundreds of kilometers or less. Little is known about the population
      genetic structure and the dispersal potential of P. damicornis in the TEP.
      METHODOLOGY: Using multilocus microsatellite data, we analyzed the population
      structure of TEP P. damicornis among and within nine reefs and test for
      significant genetic structure across three geographically and ecologically
      distinct regions in Panama. PRINCIPAL FINDINGS/CONCLUSIONS: We detected
      significant levels of population genetic structure (global R(ST) = 0.162),
      indicating restricted gene flow (i.e. larvae dispersal), both among the three
      regions (R(RT) = 0.081) as well as within regions (R(SR) = 0.089). Limited gene
      flow across a distinct environmental cline, like the regional upwelling gradient
      in Panama, indicates a significant potential for differential adaptation and
      population differentiation. Individual reefs were characterized by unexpectedly
      high genet diversity (avg. 94%), relatively high inbreeding coefficients (global
      F(IS) = 0.183), and localized spatial genetic structure among individuals (i.e.
      unique genets) over 10 m intervals. These findings suggest that gene flow is
      limited in TEP P. damicornis populations, particularly among regions, but even
      over meter scales within populations.

PMID- 21857901
TI  - A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by
      a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204).
AB  - BACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6
      plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a
      recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was
      evaluated in HIV-seronegative participants from South Africa, United States,
      Latin America and the Caribbean. METHODS: 480 participants were evenly randomized
      to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by
      rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants
      were monitored for reactogenicity and adverse events throughout the 12-month
      study. Peak and duration of HIV-specific humoral and cellular immune responses
      were evaluated after the prime and boost. RESULTS: The vaccine was well tolerated
      and safe. T-cell responses, detected by interferon-gamma (IFN-gamma) ELISpot to
      global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of
      vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In
      U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive
      versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p =
      0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by
      intracellular cytokine staining were similar (41.8% and 47.2% respectively) and
      most secreted >=2 cytokines. The vaccine induced a high frequency (83.7%-94.6%)
      of binding antibody responses to consensus Group M, and Clades A, B and C gp140
      Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine
      recipients. CONCLUSION: The vaccine regimen was well-tolerated and induced
      polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00125970.

PMID- 21857903
TI  - Integrated proteomic and transcriptomic investigation of the acetaminophen
      toxicity in liver microfluidic biochip.
AB  - Microfluidic bioartificial organs allow the reproduction of in vivo-like
      properties such as cell culture in a 3D dynamical micro environment. In this
      work, we established a method and a protocol for performing a toxicogenomic
      analysis of HepG2/C3A cultivated in a microfluidic biochip. Transcriptomic and
      proteomic analyses have shown the induction of the NRF2 pathway and the related
      drug metabolism pathways when the HepG2/C3A cells were cultivated in the biochip.
      The induction of those pathways in the biochip enhanced the metabolism of the N
      acetyl-p-aminophenol drug (acetaminophen-APAP) when compared to Petri cultures.
      Thus, we observed 50% growth inhibition of cell proliferation at 1 mM in the
      biochip, which appeared similar to human plasmatic toxic concentrations reported
      at 2 mM. The metabolic signature of APAP toxicity in the biochip showed similar
      biomarkers as those reported in vivo, such as the calcium homeostasis, lipid
      metabolism and reorganization of the cytoskeleton, at the transcriptome and
      proteome levels (which was not the case in Petri dishes). These results
      demonstrate a specific molecular signature for acetaminophen at transcriptomic
      and proteomic levels closed to situations found in vivo. Interestingly, a common
      component of the signature of the APAP molecule was identified in Petri and
      biochip cultures via the perturbations of the DNA replication and cell cycle.
      These findings provide an important insight into the use of microfluidic biochips
      as new tools in biomarker research in pharmaceutical drug studies and predictive
      toxicity investigations.

PMID- 21857904
TI  - Natural history, microbes and sequences: shouldn't we look back again to
      organisms?
AB  - The discussion on the existence of prokaryotic species is reviewed. The
      demonstration that several different mechanisms of genetic exchange and
      recombination exist has led some to a radical rejection of the possibility of
      bacterial species and, in general, the applicability of traditional
      classification categories to the prokaryotic domains. However, in spite of
      intense gene traffic, prokaryotic groups are not continuously variable but form
      discrete clusters of phenotypically coherent, well-defined, diagnosable groups of
      individual organisms. Molecularization of life sciences has led to biased
      approaches to the issue of the origins of biodiversity, which has resulted in the
      increasingly extended tendency to emphasize genes and sequences and not give
      proper attention to organismal biology. As argued here, molecular and organismal
      approaches that should be seen as complementary and not opposed views of biology.

PMID- 21857905
TI  - Recombination drives genetic diversification of Streptococcus dysgalactiae
      subspecies equisimilis in a region of streptococcal endemicity.
AB  - Infection of the skin or throat by Streptococcus dysgalactiae subspecies
      equisimilis (SDSE) may result in a number of human diseases. To understand
      mechanisms that give rise to new genetic variants in this species, we used multi
      locus sequence typing (MLST) to characterise relationships in the SDSE population
      from India, a country where streptococcal disease is endemic. The study revealed
      Indian SDSE isolates have sequence types (STs) predominantly different to those
      reported from other regions of the world. Emm-ST combinations in India are also
      largely unique. Split decomposition analysis, the presence of emm-types in
      unrelated clonal complexes, and analysis of phylogenetic trees based on
      concatenated sequences all reveal an extensive history of recombination within
      the population. The ratio of recombination to mutation (r/m) events (11:1) and
      per site r/m ratio (41:1) in this population is twice as high as reported for
      SDSE from non-endemic regions. Recombination involving the emm-gene is also more
      frequent than recombination involving housekeeping genes, consistent with
      diversification of M proteins offering selective advantages to the pathogen. Our
      data demonstrate that genetic recombination in endemic regions is more frequent
      than non-endemic regions, and gives rise to novel local SDSE variants, some of
      which may have increased fitness or pathogenic potential.

PMID- 21857906
TI  - Analysis of the waggle dance motion of honeybees for the design of a biomimetic
      honeybee robot.
AB  - The honeybee dance "language" is one of the most popular examples of information
      transfer in the animal world. Today, more than 60 years after its discovery it
      still remains unknown how follower bees decode the information contained in the
      dance. In order to build a robotic honeybee that allows a deeper investigation of
      the communication process we have recorded hundreds of videos of waggle dances.
      In this paper we analyze the statistics of visually captured high-precision dance
      trajectories of European honeybees (Apis mellifera carnica). The trajectories
      were produced using a novel automatic tracking system and represent the most
      detailed honeybee dance motion information available. Although honeybee dances
      seem very variable, some properties turned out to be invariant. We use these
      properties as a minimal set of parameters that enables us to model the honeybee
      dance motion. We provide a detailed statistical description of various dance
      properties that have not been characterized before and discuss the role of
      particular dance components in the commmunication process.

PMID- 21857902
TI  - Transcriptome sequencing of the blind subterranean mole rat, Spalax galili:
      utility and potential for the discovery of novel evolutionary patterns.
AB  - The blind subterranean mole rat (Spalax ehrenbergi superspecies) is a model
      animal for survival under extreme environments due to its ability to live in
      underground habitats under severe hypoxic stress and darkness. Here we report the
      transcriptome sequencing of Spalax galili, a chromosomal type of S. ehrenbergi.
      cDNA pools from muscle and brain tissues isolated from animals exposed to hypoxic
      and normoxic conditions were sequenced using Sanger, GS FLX, and GS FLX Titanium
      technologies. Assembly of the sequences yielded over 51,000 isotigs with homology
      to ~12,000 mouse, rat or human genes. Based on these results, it was possible to
      detect large numbers of splice variants, SNPs, and novel transcribed regions. In
      addition, multiple differential expression patterns were detected between tissues
      and treatments. The results presented here will serve as a valuable resource for
      future studies aimed at identifying genes and gene regions evolved during the
      adaptive radiation associated with underground life of the blind mole rat.

PMID- 21857907
TI  - miR-34a regulates mouse neural stem cell differentiation.
AB  - BACKGROUND: MicroRNAs (miRNAs or miRs) participate in the regulation of several
      biological processes, including cell differentiation. Recently, miR-34a has been
      implicated in the differentiation of monocyte-derived dendritic cells, human
      erythroleukemia cells, and mouse embryonic stem cells. In addition, members of
      the miR-34 family have been identified as direct p53 targets. However, the
      function of miR-34a in the control of the differentiation program of specific
      neural cell types remains largely unknown. Here, we investigated the role of miR
      34a in regulating mouse neural stem (NS) cell differentiation.
      METHODOLOGY/PRINCIPAL FINDINGS: miR-34a overexpression increased postmitotic
      neurons and neurite elongation of mouse NS cells, whereas anti-miR-34a had the
      opposite effect. SIRT1 was identified as a target of miR-34a, which may mediate
      the effect of miR-34a on neurite elongation. In addition, acetylation of p53 (Lys
      379) and p53-DNA binding activity were increased and cell death unchanged after
      miR-34a overexpression, thus reinforcing the role of p53 during neural
      differentiation. Interestingly, in conditions where SIRT1 was activated by
      pharmacologic treatment with resveratrol, miR-34a promoted astrocytic
      differentiation, through a SIRT1-independent mechanism. CONCLUSIONS: Our results
      provide new insight into the molecular mechanisms by which miR-34a modulates
      neural differentiation, suggesting that miR-34a is required for proper neuronal
      differentiation, in part, by targeting SIRT1 and modulating p53 activity.

PMID- 21857908
TI  - The effect on mental health of a large scale psychosocial intervention for
      survivors of mass violence: a quasi-experimental study in Rwanda.
AB  - BACKGROUND: War has serious and prolonged mental health consequences. It is
      argued that post-emergency mental health interventions should not only focus on
      psychological factors but also address the social environment. No controlled
      trials of such interventions exist. We studied the effect on mental health of a
      large scale psychosocial intervention primarily aimed at social bonding in post
      genocide Rwanda. The programme is implemented at population level without
      diagnostic criteria for participation. It is open to any person older than 15
      years, and enables participation of over 1500 individuals per year. We postulated
      that the mental health of programme participants would improve significantly
      relative to non-participants. METHODS AND FINDINGS: We used a prospective quasi
      experimental study design with measurement points pre and post intervention and
      at 8 months follow-up. 100 adults from both sexes in the experimental condition
      entered the study; follow-up measurements were taken from 81. We selected a
      control group of 100 respondents with similar age, sex and symptom score
      distribution from a random community sample in the same region; of these, 73
      completed the study. Mental health was assessed by use of the Self Reporting
      Questionnaire (SRQ-20), a twenty item instrument to detect common mental
      disorders in primary health care settings. Mean SRQ-20 scores decreased by 2.3
      points in the experimental group and 0.8 in the control group (p = 0.033). Women
      in the experimental group scoring above cut-off at baseline improved with 4.8
      points to below cut-off (p<0.001). Men scoring above cut-off at baseline showed a
      similar trend which was statistically non-significant. No adverse events were
      observed. CONCLUSIONS: A large scale psychosocial intervention primarily aimed at
      social bonding caused a lasting improvement of mental health in survivors of mass
      violence in Rwanda. This approach may have a similar positive effect in other
      post-conflict settings. TRIAL REGISTRATION: Nederlands Trial Register 1120.

PMID- 21857909
TI  - Real-time PyMOL visualization for Rosetta and PyRosetta.
AB  - Computational structure prediction and design of proteins and protein-protein
      complexes have long been inaccessible to those not directly involved in the
      field. A key missing component has been the ability to visualize the progress of
      calculations to better understand them. Rosetta is one simulation suite that
      would benefit from a robust real-time visualization solution. Several tools exist
      for the sole purpose of visualizing biomolecules; one of the most popular tools,
      PyMOL (Schrodinger), is a powerful, highly extensible, user friendly, and
      attractive package. Integrating Rosetta and PyMOL directly has many technical and
      logistical obstacles inhibiting usage. To circumvent these issues, we developed a
      novel solution based on transmitting biomolecular structure and energy
      information via UDP sockets. Rosetta and PyMOL run as separate processes, thereby
      avoiding many technical obstacles while visualizing information on-demand in real
      time. When Rosetta detects changes in the structure of a protein, new coordinates
      are sent over a UDP network socket to a PyMOL instance running a UDP socket
      listener. PyMOL then interprets and displays the molecule. This implementation
      also allows remote execution of Rosetta. When combined with PyRosetta, this
      visualization solution provides an interactive environment for protein structure
      prediction and design.

PMID- 21857910
TI  - Inferring a transcriptional regulatory network from gene expression data using
      nonlinear manifold embedding.
AB  - Transcriptional networks consist of multiple regulatory layers corresponding to
      the activity of global regulators, specialized repressors and activators as well
      as proteins and enzymes shaping the DNA template. Such intrinsic complexity makes
      uncovering connections difficult and it calls for corresponding methodologies,
      which are adapted to the available data. Here we present a new computational
      method that predicts interactions between transcription factors and target genes
      using compendia of microarray gene expression data and documented interactions
      between genes and transcription factors. The proposed method, called Kernel
      Embedding of Regulatory Networks (KEREN), is based on the concept of gene-regulon
      association, and captures hidden geometric patterns of the network via manifold
      embedding. We applied KEREN to reconstruct transcription regulatory interactions
      on a genome-wide scale in the model bacteria Escherichia coli (E. coli).
      Application of the method not only yielded accurate predictions of verifiable
      interactions, which outperformed on certain metrics comparable methodologies, but
      also demonstrated the utility of a geometric approach in the analysis of high
      dimensional biological data. We also described possible applications of kernel
      embedding techniques to other function and network discovery algorithms.

PMID- 21857911
TI  - A single Streptomyces symbiont makes multiple antifungals to support the fungus
      farming ant Acromyrmex octospinosus.
AB  - Attine ants are dependent on a cultivated fungus for food and use antibiotics
      produced by symbiotic Actinobacteria as weedkillers in their fungus gardens.
      Actinobacterial species belonging to the genera Pseudonocardia, Streptomyces and
      Amycolatopsis have been isolated from attine ant nests and shown to confer
      protection against a range of microfungal weeds. In previous work on the higher
      attine Acromyrmex octospinosus we isolated a Streptomyces strain that produces
      candicidin, consistent with another report that attine ants use Streptomyces
      produced candicidin in their fungiculture. Here we report the genome analysis of
      this Streptomyces strain and identify multiple antibiotic biosynthetic pathways.
      We demonstrate, using gene disruptions and mass spectrometry, that this single
      strain has the capacity to make candicidin and multiple antimycin compounds.
      Although antimycins have been known for >60 years we report the sequence of the
      biosynthetic gene cluster for the first time. Crucially, disrupting the
      candicidin and antimycin gene clusters in the same strain had no effect on
      bioactivity against a co-evolved nest pathogen called Escovopsis that has been
      identified in ~30% of attine ant nests. Since the Streptomyces strain has strong
      bioactivity against Escovopsis we conclude that it must make additional
      antifungal(s) to inhibit Escovopsis. However, candicidin and antimycins likely
      offer protection against other microfungal weeds that infect the attine fungal
      gardens. Thus, we propose that the selection of this biosynthetically prolific
      strain from the natural environment provides A. octospinosus with broad spectrum
      activity against Escovopsis and other microfungal weeds.

PMID- 21857912
TI  - Determination of the loss of function complement C4 exon 29 CT insertion using a
      novel paralog-specific assay in healthy UK and Spanish populations.
AB  - Genetic variants resulting in non-expression of complement C4A and C4B genes are
      common in healthy European populations and have shown association with a number
      of diseases, most notably the autoimmune disease, systemic lupus erythematosus.
      The most frequent cause of a C4 "null" allele, following that of C4 gene copy
      number variation (CNV), is a non-sense mutation arising from a 2 bp CT insertion
      into codon 1232 of exon 29. Previous attempts to accurately genotype this
      polymorphism have not been amenable to high-throughput typing, and have been
      confounded by failure to account for CNV at this locus, as well as by inability
      to distinguish between paralogs. We have developed a novel, high-throughput,
      paralog-specific assay to detect the presence and copy number of this
      polymorphism. We have genotyped healthy cohorts from the United Kingdom (UK) and
      Spain. Overall, 30/719 (4.17%) individuals from the UK cohort and 8/449 (1.78%)
      individuals from the Spanish cohort harboured the CT insertion in a C4A gene. A
      single Spanish individual possessed a C4B CT insertion. There is weak correlation
      between the C4 CT insertion and flanking MHC polymorphism. Therefore it is
      important to note that, as with C4 gene CNV, disease-association due to this
      variant will be missed by current SNP-based genome-wide association strategies.

PMID- 21857913
TI  - Gene expression profiling of dendritic cells reveals important mechanisms
      associated with predisposition to Staphylococcus infections.
AB  - BACKGROUND: Staphylococcus aureus is a major pathogen of humans and animals and
      emerging antibiotic-resistant strains have further increased the concern of this
      health issue. Host genetics influence susceptibility to S. aureus infections, and
      the genes determining the outcome of infections should be identified to find
      alternative therapies to treatment with antibiotics. Here, we used outbred
      animals from a divergent selection based on susceptibility towards Staphylococcus
      infection to explore host immunogenetics. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated how dendritic cells respond to heat-inactivated S. aureus and
      whether dendritic cells from animals showing different degrees of susceptibility
      had distinct gene expression profiles. We measured gene expression levels of in
      vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different
      time points (0, 3 and 8 hrs) by using 15 k ovine Agilent microarrays.
      Furthermore, differential expression of a selected number of genes was confirmed
      by RT-qPCR. Gene signatures of stimulated DCs were obtained and showed that genes
      involved in the inflammatory process and T helper cell polarization were highly
      up-regulated upon stimulation. Moreover, a set of 204 genes were statistically
      differentially expressed between susceptible and resistant animals, and grouped
      them according to their predisposition to staphylococcal infection.
      Interestingly, over-expression of the C1q and Ido1 genes was observed in the
      resistant line and suggested a role of classical pathway of complement and early
      regulation of inflammation pathways, respectively. On the contrary, over
      expression of genes involved in the IL1R pathway was observed in susceptible
      animals. Furthermore, the leucocyte extravasation pathway was also found to be
      dominant in the susceptible line. CONCLUSION/SIGNIFICANCE: We successfully
      obtained Staphylococcus aureus associated gene expression of ovine BM-DC in an 8
      hour kinetics experiment. The distinct transcriptional profiles of dendritic
      cells obtained from resistant and susceptible animals may explain susceptibility
      towards S. aureus infections in a broader context.

PMID- 21857914
TI  - RNA-binding domain in the nucleocapsid protein of gill-associated nidovirus of
      penaeid shrimp.
AB  - Gill-associated virus (GAV) infects Penaeus monodon shrimp and is the type
      species okavirus in the Roniviridae, the only invertebrate nidoviruses known
      currently. Electrophoretic mobility shift assays (EMSAs) using His(6)-tagged full
      length and truncated proteins were employed to examine the nucleic acid binding
      properties of the GAV nucleocapsid (N) protein in vitro. The EMSAs showed full
      length N protein to bind to all synthetic single-stranded (ss)RNAs tested
      independent of their sequence. The ssRNAs included (+) and (-) sense regions of
      the GAV genome as well as a (+) sense region of the M RNA segment of Mourilyan
      virus, a crustacean bunya-like virus. GAV N protein also bound to double-stranded
      (ds)RNAs prepared to GAV ORF1b gene regions and to bacteriophage M13 genomic
      ssDNA. EMSAs using the five N protein constructs with variable-length N-terminal
      and/or C-terminal truncations localized the RNA binding domain to a 50 amino acid
      (aa) N-terminal sequence spanning Met(11) to Arg(60). Similarly to other RNA
      binding proteins, the first 16 aa portion of this sequence was proline/arginine
      rich. To examine this domain in more detail, the 18 aa peptide
      (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found
      to bind nucleic acids similarly to the full-length N protein in EMSAs. The data
      indicate a fundamental role for the GAV N protein proline/arginine-rich domain in
      nucleating genomic ssRNA to form nucleocapsids. Moreover, as the synthetic
      peptide formed higher-order complexes in the presence of RNA, the domain might
      also play some role in protein/protein interactions stabilizing the helical
      structure of GAV nucleocapsids.

PMID- 21857915
TI  - Kinetic theory approach to modeling of cellular repair mechanisms under genome
      stress.
AB  - Under acute perturbations from outer environment, a normal cell can trigger
      cellular self-defense mechanism in response to genome stress. To investigate the
      kinetics of cellular self-repair process at single cell level further, a model of
      DNA damage generating and repair is proposed under acute Ion Radiation (IR) by
      using mathematical framework of kinetic theory of active particles (KTAP).
      Firstly, we focus on illustrating the profile of Cellular Repair System (CRS)
      instituted by two sub-populations, each of which is made up of the active
      particles with different discrete states. Then, we implement the mathematical
      framework of cellular self-repair mechanism, and illustrate the dynamic processes
      of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein
      complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly
      analyze the capability of cellular self-repair mechanism, cellular activity of
      transferring DNA damage, and genome stability, especially the different fates of
      a certain cell before and after the time thresholds of IR perturbations that a
      cell can tolerate maximally under different IR perturbation circumstances.

PMID- 21857916
TI  - Examining the effects of one- and three-dimensional spatial filtering analyses in
      magnetoencephalography.
AB  - Spatial filtering, or beamforming, is a commonly used data-driven analysis
      technique in the field of Magnetoencephalography (MEG). Although routinely
      referred to as a single technique, beamforming in fact encompasses several
      different methods, both with regard to defining the spatial filters used to
      reconstruct source-space time series and in terms of the analysis of these time
      series. This paper evaluates two alternative methods of spatial filter
      construction and application. It demonstrates how encoding different requirements
      into the design of these filters has an effect on the results obtained. The
      analyses presented demonstrate the potential value of implementations which
      examine the timeseries projections in multiple orientations at a single location
      by showing that beamforming can reconstruct predominantly radial sources in the
      case of a multiple-spheres forward model. The accuracy of source reconstruction
      appears to be more related to depth than source orientation. Furthermore, it is
      shown that using three 1-dimensional spatial filters can result in inaccurate
      source-space time series reconstruction. The paper concludes with brief
      recommendations regarding reporting beamforming methodologies in order to help
      remove ambiguity about the specifics of the techniques which have been used.

PMID- 21857917
TI  - RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx
      induced NF-kappaB signaling via its novel chaperoning function.
AB  - Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular
      carcinoma (HCC) development. Hepatitis B virus X protein (HBx) is known to play a
      key role in the development of hepatocellular carcinoma (HCC). Several cellular
      proteins have been reported to be over-expressed in HBV-associated HCC tissues,
      but their role in the HBV-mediated oncogenesis remains largely unknown. Here, we
      explored the effect of the over-expressed cellular protein, a ribosomal protein
      S3a (RPS3a), on the HBx-induced NF-kappaB signaling as a critical step for HCC
      development. The enhancement of HBx-induced NF-kappaB signaling by RPS3a was
      investigated by its ability to translocate NF-kappaB (p65) into the nucleus and
      the knock-down analysis of RPS3a. Notably, further study revealed that the
      enhancement of NF-kappaB by RPS3a is mediated by its novel chaperoning activity
      toward physiological HBx. The over-expression of RPS3a significantly increased
      the solubility of highly aggregation-prone HBx. This chaperoning function of
      RPS3a for HBx is closely correlated with the enhanced NF-kappaB activity by
      RPS3a. In addition, the mutational study of RPS3a showed that its N-terminal
      domain (1-50 amino acids) is important for the chaperoning function and
      interaction with HBx. The results suggest that RPS3a, via extra-ribosomal
      chaperoning function for HBx, contributes to virally induced oncogenesis by
      enhancing HBx-induced NF-kappaB signaling pathway.

PMID- 21857918
TI  - Assessing arboreal adaptations of bird antecedents: testing the ecological
      setting of the origin of the avian flight stroke.
AB  - The origin of avian flight is a classic macroevolutionary transition with
      research spanning over a century. Two competing models explaining this locomotory
      transition have been discussed for decades: ground up versus trees down. Although
      it is impossible to directly test either of these theories, it is possible to
      test one of the requirements for the trees-down model, that of an arboreal
      paravian. We test for arboreality in non-avian theropods and early birds with
      comparisons to extant avian, mammalian, and reptilian scansors and climbers using
      a comprehensive set of morphological characters. Non-avian theropods, including
      the small, feathered deinonychosaurs, and Archaeopteryx, consistently and
      significantly cluster with fully terrestrial extant mammals and ground-based
      birds, such as ratites. Basal birds, more advanced than Archaeopteryx, cluster
      with extant perching ground-foraging birds. Evolutionary trends immediately prior
      to the origin of birds indicate skeletal adaptations opposite that expected for
      arboreal climbers. Results reject an arboreal capacity for the avian stem
      lineage, thus lending no support for the trees-down model. Support for a fully
      terrestrial ecology and origin of the avian flight stroke has broad implications
      for the origin of powered flight for this clade. A terrestrial origin for the
      avian flight stroke challenges the need for an intermediate gliding phase,
      presents the best resolved series of the evolution of vertebrate powered flight,
      and may differ fundamentally from the origin of bat and pterosaur flight, whose
      antecedents have been postulated to have been arboreal and gliding.

PMID- 21857919
TI  - Evaluation of 15 functional candidate genes for association with chronic otitis
      media with effusion and/or recurrent otitis media (COME/ROM).
AB  - DNA sequence variants in genes involved in the innate immune response and
      secondary response to infection may confer susceptibility to chronic otitis media
      with effusion and/or recurrent otitis media (COME/ROM). We evaluated single
      nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99
      SNPs were successfully genotyped on the Sequenom platform in 142 families (618
      subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for
      association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex
      and age at exam were adjusted as covariates, relatedness was accounted for, and
      genotype differences from all phenotypically discordant relative pairs were
      utilized to measure the evidence of association between COME/ROM and each SNP.
      SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited
      nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs
      from this region had P values<0.05. Other variants exhibiting associations with
      COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP
      rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these
      associations replicated in an independent sample of COME/ROM families. The
      candidate gene variants examined do not appear to make a major contribution to
      COME/ROM susceptibility, despite a priori evidence from functional or animal
      model studies for a role in COME/ROM pathology.

PMID- 21857920
TI  - Validation of endogenous control genes for gene expression studies on human
      ocular surface epithelium.
AB  - PURPOSE: To evaluate a panel of ten known endogenous control genes (ECG) with
      quantitative reverse transcription PCR (qPCR), for identification of stably
      expressed endogenous control genes in the ocular surface (OS) epithelial regions
      including cornea, limbus, limbal epithelial crypt and conjunctiva to normalise
      the quantitative reverse transcription PCR data of genes of interest expressed in
      above-mentioned regions. METHOD: The lasermicrodissected (LMD) OS epithelial
      regions of cryosectioned corneoscleral buttons from the cadaver eyes were
      processed for RNA extraction and cDNA synthesis to detect genes of interest with
      qPCR. Gene expression of 10 known ECG--glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), beta actin (ACTB), peptidylprolyl isomerase (PPIA), TATA-box binding
      protein (TBP1), hypoxanthine guanine phosphoribosyl transferase (HPRT1), beta
      glucuronidase (GUSB), Eucaryotic 18S ribosomal RNA (18S), phosphoglycerate kinase
      (PGK1), beta-2-microglobulin (B2M), ribosomal protein, large, P0 (RPLP0)--was
      measured in the OS epithelial regions by qPCR method and the data collected was
      further analysed using geNorm software. RESULTS: The expression stability of ecgs
      in the os epithelial regions in increasing order as determined with genorm
      software is as follows: ACTB<18S<TBP<B2M<PGK1<HPRT1<GUSB<GAPDH<PPIA-RPLP0. In
      this study, geNorm analysis has shown the following ECGs pairs to be most stably
      expressed in individual OS epithelial regions: HPRT1-TBP in cornea, GUSB-PPIA in
      limbus, B2M-PPIA and RPLP0-TBP in LEC and conjunctiva respectively. However,
      across the entire ocular surface including all the regions mentioned above, PPIA
      RPLP0 pair was shown to be most stable. CONCLUSION: This study has identified
      stably expressed ECGs on the OS epithelial regions for effective qPCR results in
      genes of interest. The results from this study are broadly applicable to
      quantitative reverse transcription PCR studies on human OS epithelium and provide
      evidence for the use of PPIA-RPLP0 ECGs pair in quantitative reverse
      transcription PCR across the OS epithelium.

PMID- 21857921
TI  - A twin study of mitochondrial DNA polymorphisms shows that heteroplasmy at
      multiple sites is associated with mtDNA variant 16093 but not with zygosity.
AB  - The mitochondrial theory of ageing proposes that damage to mitochondria and
      diminished mitochondrial DNA (mtDNA) repair are major contributors to cellular
      dysfunction and age-related diseases. We investigate the prevalence of
      heteroplasmy in the mtDNA control region in buccal swab and blood derived samples
      for 178 women from the TwinsUK cohort (41 DZ pair 39 MZ pairs, 18 singletons,
      mean age 57.5 range 28-82) and its relationship to age, BMI and fasting insulin
      and glucose serum levels. The overall estimated prevalence of heteroplasmy for
      both tissues in the control region measured for 37 sites was 17%. The prevalence
      of heteroplasmy was higher among the older half of the study subjects than in the
      younger half (23% vs 10% p<0.03), primarily reflecting the increase in the
      prevalence of a heteroplasmic dinucleotide CA repeat in variable region II (VRII)
      with age. The VRII 523-524 heteroplasmic site (heteroplasmic in 25 subjects) was
      also associated with a decrease in BMI. In addition, concordance rates for common
      heteroplasmy were observed to be near complete for both dizygotic (DZ = 94%) and
      monozygotic twin pairs (MZ = 100%), consistent with previous reports that suggest
      variation in heteroplasmy rates between generations are determined by bottlenecks
      in maternal transmission of mitochondria. Differences in the prevalence of
      heteroplasmy were observed overall between samples derived from buccal swabs
      (19%) and blood (15%, p<0.04). These were particularly marked at position 16093
      of hypervariable region I (HVI, 7% vs 0%, respectively, p<4*10(-11)). The
      presence of the C allele at position 16093 in blood was associated with the
      presence of heteroplasmy in buccal swabs at this position (p = 3.5*10(-14)) and
      also at VRII (p = 2*10(-4)) suggesting a possible predisposing role for this site
      in the accumulation of heteroplasmy. Our data indicate that BMI is potentially
      associated with control region heteroplasmy.

PMID- 21857922
TI  - Network stability is a balancing act of personality, power, and conflict dynamics
      in rhesus macaque societies.
AB  - Stability in biological systems requires evolved mechanisms that promote
      robustness. Cohesive primate social groups represent one example of a stable
      biological system, which persist in spite of frequent conflict. Multiple sources
      of stability likely exist for any biological system and such robustness, or lack
      thereof, should be reflected and thus detectable in the group's network
      structure, and likely at multiple levels. Here we show how network structure and
      group stability are linked to the fundamental characteristics of the individual
      agents in groups and to the environmental and social contexts in which these
      individuals interact. Both internal factors (e.g., personality, sex) and external
      factors (e.g., rank dynamics, sex ratio) were considered from the level of the
      individual to that of the group to examine the effects of network structure on
      group stability in a nonhuman primate species. The results yielded three main
      findings. First, successful third-party intervention behavior is a mechanism of
      group stability in rhesus macaques in that successful interventions resulted in
      less wounding in social groups. Second, personality is the primary factor that
      determines which individuals perform the role of key intervener, via its effect
      on social power and dominance discrepancy. Finally, individuals with high social
      power are not only key interveners but also key players in grooming networks and
      receive reconciliations from a higher diversity of individuals. The results from
      this study provide sound evidence that individual and group characteristics such
      as personality and sex ratio influence network structures such as patterns of
      reconciliation, grooming and conflict intervention that are indicators of network
      robustness and consequent health and well-being in rhesus macaque societies.
      Utilizing this network approach has provided greater insight into how behavioral
      and social processes influence social stability in nonhuman primate groups.

PMID- 21857923
TI  - Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to
      dopaminergic neuron degeneration in C. elegans.
AB  - Mutation of leucine-rich repeat kinase 2 (LRRK2) is the leading genetic cause of
      Parkinson's Disease (PD), manifested as age-dependent dopaminergic
      neurodegeneration, but the underlying molecular mechanisms remain unclear.
      Multiple roles of LRRK2 may contribute to dopaminergic neurodegeneration.
      Endoplasmic reticulum (ER) stress has also been linked to PD pathogenesis, but
      its interactive mechanism with PD genetic factors is largely unknown. Here, we
      used C. elegans, human neuroblastoma cells and murine cortical neurons to
      determine the role of LRRK2 in maintaining dopaminergic neuron viability. We
      found that LRRK2 acts to protect neuroblastoma cells and C. elegans dopaminergic
      neurons from the toxicity of 6-hydroxydopamine and/or human alpha-synuclein,
      possibly through the p38 pathway, by supporting upregulation of GRP78, a key cell
      survival molecule during ER stress. A pathogenic LRRK2 mutant (G2019S), however,
      caused chronic p38 activation that led to death of murine neurons and age-related
      dopaminergic-specific neurodegeneration in nematodes. These observations
      establish a critical functional link between LRRK2 and ER stress.

PMID- 21857924
TI  - TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic
      insulin expression and changes in islet morphology.
AB  - Alongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to
      be instrumental in the maintenance of the beta cell phenotype. Indeed, a
      combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was
      recently reported to lead to the effective reprogramming of acinar cells into
      insulin-producing beta cells. These experiments set the stage for the development
      of new strategies to address the impairment of glycemic control in diabetic
      patients. However, the clinical applicability of reprogramming in this context is
      deemed to be poor due to the need to use viral vehicles for the delivery of the
      above factors. Here we describe a recombinant transducible version of the MafA
      protein (TAT-MafA) that penetrates across cell membranes with an efficiency of
      100% and binds to the insulin promoter in vitro. When injected in utero into
      living mouse embryos, TAT-MafA significantly up-regulates target genes and
      induces enhanced insulin production as well as cytoarchitectural changes
      consistent with faster islet maturation. As the latest addition to our
      armamentarium of transducible proteins (which already includes Pdx1 and Ngn3),
      the purification and characterization of a functional TAT-MafA protein opens the
      door to prospective therapeutic uses that circumvent the use of viral delivery.
      To our knowledge, this is also the first report on the use of protein
      transduction in utero.

PMID- 21857925
TI  - Homing pigeons only navigate in air with intact environmental odours: a test of
      the olfactory activation hypothesis with GPS data loggers.
AB  - A large body of evidence has shown that anosmic pigeons are impaired in their
      navigation. However, the role of odours in navigation is still subject to debate.
      While according to the olfactory navigation hypothesis homing pigeons possess a
      navigational map based on the distribution of environmental odours, the olfactory
      activation hypothesis proposes that odour perception is only needed to activate a
      navigational mechanism based on cues of another nature. Here we tested
      experimentally whether the perception of artificial odours is sufficient to allow
      pigeons to navigate, as expected from the olfactory activation hypothesis. We
      transported three groups of pigeons in air-tight containers to release sites 53
      and 61 km from home in three different olfactory conditions. The Control group
      received natural environmental air; both the Pure Air and the Artificial Odour
      groups received pure air filtered through an active charcoal filter. Only the
      Artificial Odour group received additional puffs of artificial odours until
      release. We then released pigeons while recording their tracks with 1 Hz GPS data
      loggers. We also followed non-homing pigeons using an aerial data readout to a
      Cessna plane, allowing, for the first time, the tracking of non-homing homing
      pigeons. Within the first hour after release, the pigeons in both the Artificial
      Odour and the Pure Air group (receiving no environmental odours) showed impaired
      navigational performances at each release site. Our data provide evidence against
      an activation role of odours in navigation, and document that pigeons only
      navigate well when they perceive environmental odours.

PMID- 21857926
TI  - Activation of nicotinic cholinergic receptors prevents ventilator-induced lung
      injury in rats.
AB  - Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An
      over mortality of about 10 percent could result from additional lung injury and
      inflammation due to the life-support mechanical ventilation, which stretches the
      lung. It has been recently demonstrated, in vitro, that pharmacological
      activation of the alpha 7 nicotinic receptors (alpha7-nAChR) could down regulate
      intracellular mediators involved in lung cell inflammatory response to stretch.
      Our aim was to test in vivo the protective effect of the pharmacological
      activation of the alpha7-nAChR against ventilator-induced lung injury (VILI).
      Anesthetized rats were ventilated for two hours with a high stretch ventilation
      mode delivering a stroke volume large enough to generate 25-cmH(2)O airway
      pressure, and randomly assigned to four groups: pretreated with parenteral
      injection of saline or specific agonist of the alpha7-nAChR (PNU-282987), or
      submitted to bilateral vagus nerve electrostimulation while pre-treated or not
      with the alpha7-nAChR antagonist methyllycaconitine (MLA). Controls ventilated
      with a conventional stroke volume of 10 mL/kg gave reference data. Physiological
      indices (compliance of the respiratory system, lung weight, blood oxygenation,
      arterial blood pressure) and lung contents of inflammatory mediators (IL-6
      measured by ELISA, substance P assessed using HPLC) were severely impaired after
      two hours of high stretch ventilation (sham group). Vagal stimulation was able to
      maintain the respiratory parameters close to those obtained in Controls and
      reduced lung inflammation except when associated to nicotinic receptor blockade
      (MLA), suggesting the involvement of alpha7-nAChR in vagally-mediated protection
      against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased
      lung injury and lung IL-6 and substance P contents, and nearly abolished the
      increase in plasmatic IL-6 levels. Pathological examination of the lungs
      confirmed the physiological differences observed between the groups. In
      conclusion, these data suggest that the stimulation of alpha7-nAChR is able to
      attenuate VILI in rats.

PMID- 21857927
TI  - Survivorship of Anopheles darlingi (Diptera: Culicidae) in relation with malaria
      incidence in the Brazilian Amazon.
AB  - We performed a longitudinal study of adult survival of Anopheles darlingi, the
      most important vector in the Amazon, in a malarigenous frontier zone of Brazil.
      Survival rates were determined from both parous rates and multiparous
      dissections. Anopheles darlingi human biting rates, daily survival rates and
      expectation of life where higher in the dry season, as compared to the rainy
      season, and were correlated with malaria incidence. The biting density of
      mosquitoes that had survived long enough for completing at least one sporogonic
      cycle was related with the number of malaria cases by linear regression. Survival
      rates were the limiting factor explaining longitudinal variations in Plasmodium
      vivax malaria incidence and the association between adult mosquito survival and
      malaria was statistically significant by logistic regression (P<0.05). Survival
      rates were better correlated with malaria incidence than adult mosquito biting
      density. Mathematical modeling showed that P. falciparum and P. malariae were
      more vulnerable to changes in mosquito survival rates because of longer
      sporogonic cycle duration, as compared to P. vivax, which could account for the
      low prevalence of the former parasites observed in the study area. Population
      modeling also showed that the observed decreases in human biting rates in the wet
      season could be entirely explained by decreases in survival rates, suggesting
      that decreased breeding did not occur in the wet season, at the sites where adult
      mosquitoes were collected. For the first time in the literature, multivariate
      methods detected a statistically significant inverse relation (P<0.05) between
      the number of rainy days per month and daily survival rates, suggesting that
      rainfall may cause adult mortality.

PMID- 21857928
TI  - Survey of Canadian animal-based researchers' views on the Three Rs: replacement,
      reduction and refinement.
AB  - The 'Three Rs' tenet (replacement, reduction, refinement) is a widely accepted
      cornerstone of Canadian and international policies on animal-based science. The
      Canadian Council on Animal Care (CCAC) initiated this web-based survey to obtain
      greater understanding of 'principal investigators' and 'other researchers' (i.e.
      graduate students, post-doctoral researchers etc.) views on the Three Rs, and to
      identify obstacles and opportunities for continued implementation of the Three Rs
      in Canada. Responses from 414 participants indicate that researchers currently do
      not view the goal of replacement as achievable. Researchers prefer to use enough
      animals to ensure quality data is obtained rather than using the minimum and
      potentially waste those animals if a problem occurs during the study. Many feel
      that they already reduce animal numbers as much as possible and have concerns
      that further reduction may compromise research. Most participants were ambivalent
      about re-use, but expressed concern that the practice could compromise
      experimental outcomes. In considering refinement, many researchers feel there are
      situations where animals should not receive pain relieving drugs because it may
      compromise scientific outcomes, although there was strong support for the Three
      Rs strategy of conducting animal welfare-related pilot studies, which were viewed
      as useful for both animal welfare and experimental design. Participants were not
      opposed to being offered "assistance" to implement the Three Rs, so long as the
      input is provided in a collegial manner, and from individuals who are perceived
      as experts. It may be useful for animal use policymakers to consider what steps
      are needed to make replacement a more feasible goal. In addition, initiatives
      that offer researchers greater practical and logistical support with Three Rs
      implementation may be useful. Encouragement and financial support for Three Rs
      initiatives may result in valuable contributions to Three Rs knowledge and
      improve welfare for animals used in science.

PMID- 21857929
TI  - Influence of marital status and employment status on long-term adherence with
      continuous positive airway pressure in sleep apnea patients.
AB  - BACKGROUND: Long-term adherence is a major issue in patients receiving home
      continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea
      hypopnea syndrome (OSAHS). In a multicenter prospective cohort (the Institut de
      Recherche en Sante Respiratoire des Pays de la Loire [IRSR] sleep cohort) of
      consecutive OSAHS patients in whom CPAP had been prescribed for at least 90 days,
      we studied the impact on long-term treatment adherence of socioeconomic factors,
      patients and disease characteristics prior to CPAP initiation. METHODS AND
      PRINCIPAL FINDINGS: Among 1,141 patients in whom CPAP had been prescribed for an
      average of 504+/-251 days (range: 91 to 1035), 674 (59%) were adherent with a
      mean daily use of CPAP>=4 h (mean: 6.42+/-1.35 h). Stepwise regression analysis
      identified 4 independent factors of CPAP adherence including apnea-hypopnea index
      (AHI) (OR: 1.549, 95%CI 1.163 to 2.062 for AHI>=30 vs. AHI<30; p = 0.003), body
      mass index (BMI) (OR: 1.786, 95%CI 1.131 to 2.822 for BMI>=25 and <30 kg/m(2), p
      = 0.01; OR: 1.768, 95%CI 1.145-2.731 for BMI>=30 kg/m(2), p = 0.01 vs. BMI<25
      kg/m(2)), employment status (OR: 1.414, 95%CI 1.097-1.821 for retired vs.
      employed; p = 0.007) and marital status (OR: 1.482, 95%CI 1.088-2.019 for married
      or living as a couple vs. living alone; p = 0.01). Age, gender, Epworth
      sleepiness scale, depressive syndrome, associated cardiovascular morbidities,
      educational attainment and occupation category did not influence CPAP adherence.
      CONCLUSIONS: Marital status and employment status are independent factors of CPAP
      adherence in addition to BMI and disease severity. Patients living alone and/or
      working patients are at greater risk of non-adherence, whereas adherence is
      higher in married and retired patients. These findings suggest that the social
      context of daily life should be taken into account in risk screening for CPAP non
      adherence. Future interventional studies targeting at-risk patients should be
      designed to address social motivating factors and work-related barriers to CPAP
      adherence.

PMID- 21857930
TI  - MIRTFnet: analysis of miRNA regulated transcription factors.
AB  - BACKGROUND: Several expression datasets of miRNA transfection experiments are
      available to analyze the regulatory mechanisms downstream of miRNA effects. The
      miRNA induced regulatory effects can be propagated via transcription factors
      (TFs). We propose the method MIRTFnet to identify miRNA controlled TFs as active
      regulators if their downstream target genes are differentially expressed.
      METHODOLOGY/PRINCIPAL FINDINGS: MIRTFnet enables the determination of active
      transcription factors (TFs) and is sensitive enough to exploit the small
      expression changes induced by the activity of miRNAs. For this purpose, different
      statistical tests were evaluated and compared. Based on the identified TFs,
      databases, computational predictions and the literature we construct regulatory
      models downstream of miRNA actions. Transfecting miRNAs are connected to active
      regulators via a network of miRNA-TF, miRNA-kinase-TF as well as TF-TF
      relationships. Based on 43 transfection experiments involving 17 cancer relevant
      miRNAs we show that MIRTFnet detects active regulators reliably.
      CONCLUSIONS/SIGNIFICANCE: The consensus of the individual regulatory models shows
      that the examined miRNAs induce activity changes in a common core of
      transcription factors involved in cancer related processes such as proliferation
      or apoptosis.

PMID- 21857931
TI  - rst transcriptional activity influences kirre mRNA concentration in the
      Drosophila pupal retina during the final steps of ommatidial patterning.
AB  - BACKGROUND: Drosophila retinal architecture is laid down between 24-48 hours
      after puparium formation, when some of the still uncommitted interommatidial
      cells (IOCs) are recruited to become secondary and tertiary pigment cells while
      the remaining ones undergo apoptosis. This choice between survival and death
      requires the product of the roughest (rst) gene, an immunoglobulin superfamily
      transmembrane glycoprotein involved in a wide range of developmental processes.
      Both temporal misexpression of Rst and truncation of the protein intracytoplasmic
      domain, lead to severe defects in which IOCs either remain mostly
      undifferentiated and die late and erratically or, instead, differentiate into
      extra pigment cells. Intriguingly, mutants not expressing wild type protein often
      have normal or very mild rough eyes. METHODOLOGY/PRINCIPAL FINDINGS: By using
      quantitative real time PCR to examine rst transcriptional dynamics in the pupal
      retina, both in wild type and mutant alleles we showed that tightly regulated
      temporal changes in rst transcriptional rate underlie its proper function during
      the final steps of eye patterning. Furthermore we demonstrated that the
      unexpected wild type eye phenotype of mutants with low or no rst expression
      correlates with an upregulation in the mRNA levels of the rst paralogue kin-of
      irre (kirre), which seems able to substitute for rst function in this process,
      similarly to their role in myoblast fusion. This compensatory upregulation of
      kirre mRNA levels could be directly induced in wild type pupa upon RNAi-mediated
      silencing of rst, indicating that expression of both genes is also coordinately
      regulated in physiological conditions. CONCLUSIONS/SIGNIFICANCE: These findings
      suggest a general mechanism by which rst and kirre expression could be fine tuned
      to optimize their redundant roles during development and provide a clearer
      picture of how the specification of survival and apoptotic fates by differential
      cell adhesion during the final steps of retinal morphogenesis in insects are
      controlled at the transcriptional level.

PMID- 21857932
TI  - HbA1c of 6.5% to diagnose diabetes mellitus -- does it work for us? -- the
      Bellville South Africa study.
AB  - BACKGROUND: HbA1c has been the gold standard for glycaemic control follow-up for
      decades. In 2009, a level of 6.5% (48 mmol/mol) was proposed as diagnostic for
      diabetes. We test this cut-off in our community. METHODS: Participants (946) from
      a community-based study were screened for diabetes using either a fasting blood
      glucose or oral glucose tolerance test (OFTT). The HbA1c cut-off of 6.5% was
      tested for each group. A receiver operator characteristic (ROC) curve for both
      groups was generated to establish an optimal cut-off. RESULTS: Our study included
      224 (23.7%) males and 722 (76.3%) females. Using fasting blood glucose alone, 117
      (14%) were diagnosed with diabetes--50% had an HbA1c value of >=6.5% (48
      mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes--46% had an
      HbA1c value of >=6.5% (48 mmol/mol). ROC curves found a level of 6.1% (43
      mmol/mol) to be optimal in both groups (AUC 0.85 and 0.82 respectively). The
      sensitivities were 80% and 75% and the specificities 77% and 78% respectively.
      CONCLUSIONS: A cut off of 6.5% (48 mmol/mol) is a good diagnostic tool with its
      high specificity; however the low sensitivity limits its use. We found a level of
      6.1% (43 mmol/mol) to be optimal. This emphasizes the need for evidenced based
      values to be established in various population groups.

PMID- 21857933
TI  - Association of NT-proBNP and multiple biomarkers with severity of angiographic
      coronary artery disease in diabetic and pre-diabetic Chinese patients.
AB  - BACKGROUND: Little is known about the plasma levels of N-terminal pro-brain
      natriuretic peptide (NT-proBNP), and the relationship between the severity of
      coronary heart disease (CHD) with NT-proBNP and multiple biomarkers in diabetic
      and pre-diabetic patients, compared to individuals with normal glucose levels.
      METHODS: Four hundred and fifteen consecutive Chinese patients of both sexes were
      assigned to three groups on the basis of the new hemoglobin (Hb) A1c (HbA1c) cut
      off points for diagnosis of diabetes and pre-diabetes. The three groups were
      divided into tertiles according to NT-proBNP, hs-CRP, cystatin C, and troponin T
      levels. Gensini scores were compared among the three groups and biomarker
      tertiles. Receiver operating characteristic (ROC) curves were used to obtain the
      angiographic CHD cut-off points for each biomarker. Stepwise multivariate linear
      correlation analysis was applied to examine the association between the severity
      of CHD and biomarker levels. RESULTS: Gensini scores increased with increasing
      biomarker tertile levels and HbA1c. Gensini scores were significantly different
      in the middle and upper NT-proBNP tertiles of the diabetic, pre-diabetic and
      control groups. NT-proBNP had the highest positive and negative predictive values
      and area under the curve for CHD. Only NT-proBNP was identified as an independent
      variable for Gensini score. CONCLUSIONS: Plasma NT-proBNP may be an important
      biomarker to evaluate the severity of CHD and screen for CHD in diabetic or pre
      diabetic patients.

PMID- 21857934
TI  - Calcium prevents tumorigenesis in a mouse model of colorectal cancer.
AB  - BACKGROUND AND AIM: Calcium has been proposed as a mediator of the
      chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism
      underlying this preventive effect is not yet clear. Hence, we conducted this
      study to evaluate the possible roles and mechanisms of calcium-mediated
      prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice. METHODS: For
      gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH +
      Calcium group and 3 samples each from the DMH and control groups were hybridized
      on a 4*44 K Agilent whole genome oligo microarray, and selected genes were
      validated by real-time polymerase chain reaction (PCR). Functional analysis of
      the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub
      genes were identified using Pathway Studio software. RESULTS: The tumor incidence
      rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively.
      Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7,
      Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef,
      Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group
      compared with the DMH group. Functional analysis showed that the Wnt, cell cycle,
      and arachidonic acid pathways were significantly downregulated in the DMH +
      Calcium group, and that the GO terms related to cell differentiation, cell cycle,
      proliferation, cell death, adhesion, and cell migration were significantly
      affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-kappaB) were
      considered as potent hub genes. CONCLUSION: In the DMH-induced CRC mouse model,
      comprehensive mechanisms were involved with complex gene expression alterations
      encompassing many altered pathways and GO terms. However, how calcium regulates
      these events remains to be studied.

PMID- 21857935
TI  - Early elevation of matrix metalloproteinase-8 and -9 in pediatric ARDS is
      associated with an increased risk of prolonged mechanical ventilation.
AB  - BACKGROUND: Matrix metalloproteinases (MMP) -8 and -9 may play key roles in the
      modulation of neutrophilic lung inflammation seen in pediatric Acute Respiratory
      Distress Syndrome (ARDS). We aimed to perform a comprehensive analysis of MMP-8
      and MMP-9 activity in tracheal aspirates of pediatric ARDS patients compared with
      non-ARDS controls, testing whether increased MMP-8 and -9 activities were
      associated with clinical outcomes. METHODS: Tracheal aspirates were collected
      from 33 pediatric ARDS patients and 21 non-ARDS controls at 48 hours of
      intubation, and serially for those who remained intubated greater than five days.
      MMPs, tissue inhibitor of metalloproteinases (TIMPs), human neutrophil elastase
      (HNE) and myeloperoxidase (MPO) activity were measured by ELISA, and correlated
      with clinical indicators of disease severity such as PRISM (Pediatric Risk of
      Mortality) scores, oxygen index (OI), multi-organ system failure (MOSF) and
      clinical outcome measures including length of intubation, ventilator-free days
      (VFDs) and mortality in the Pediatric Intensive Care Unit (PICU). RESULTS: Active
      MMP-9 was elevated early in pediatric ARDS subjects compared to non-ARDS
      controls. Higher MMP-8 and active MMP-9 levels at 48 hours correlated with a
      longer course of mechanical ventilation (r = 0.41, p = 0.018 and r = 0.75,
      p<0.001; respectively) and fewer number of VFDs (r = -0.43, p = 0.013 and r = 
      0.76, p<0.001; respectively), independent of age, gender and severity of illness.
      Patients with the highest number of ventilator days had the highest levels of
      active MMP-9. MMP-9 and to a lesser extent MMP-8 activities in tracheal aspirates
      from ARDS subjects were sensitive to blockade by small molecule inhibitors.
      CONCLUSIONS: Higher MMP-8 and active MMP-9 levels at 48 hours of disease onset
      are associated with a longer duration of mechanical ventilation and fewer
      ventilator-free days among pediatric patients with ARDS. Together, these results
      identify early biomarkers predictive of disease course and potential therapeutic
      targets for this life threatening disease.

PMID- 21857937
TI  - Discrete dynamics model for the speract-activated Ca2+ signaling network relevant
      to sperm motility.
AB  - Understanding how spermatozoa approach the egg is a central biological issue.
      Recently a considerable amount of experimental evidence has accumulated on the
      relation between oscillations in intracellular calcium ion concentration
      ([Ca2+]i) in the sea urchin sperm flagellum, triggered by peptides secreted from
      the egg, and sperm motility. Determination of the structure and dynamics of the
      signaling pathway leading to these oscillations is a fundamental problem.
      However, a biochemically based formulation for the comprehension of the molecular
      mechanisms operating in the axoneme as a response to external stimulus is still
      lacking. Based on experiments on the S. purpuratus sea urchin spermatozoa, we
      propose a signaling network model where nodes are discrete variables
      corresponding to the pathway elements and the signal transmission takes place at
      discrete time intervals according to logical rules. The validity of this model is
      corroborated by reproducing previous empirically determined signaling features.
      Prompted by the model predictions we performed experiments which identified novel
      characteristics of the signaling pathway. We uncovered the role of a high voltage
      activated Ca2+ channel as a regulator of the delay in the onset of fluctuations
      after activation of the signaling cascade. This delay time has recently been
      shown to be an important regulatory factor for sea urchin sperm reorientation.
      Another finding is the participation of a voltage-dependent calcium-activated K+
      channel in the determination of the period of the [Ca2+]i fluctuations.
      Furthermore, by analyzing the spread of network perturbations we find that it
      operates in a dynamically critical regime. Our work demonstrates that a coarse
      grained approach to the dynamics of the signaling pathway is capable of revealing
      regulatory sperm navigation elements and provides insight, in terms of
      criticality, on the concurrence of the high robustness and adaptability that the
      reproduction processes are predicted to have developed throughout evolution.

PMID- 21857936
TI  - Diversification and species boundaries of Rhinebothrium (Cestoda;
      Rhinebothriidea) in South American freshwater stingrays (Batoidea;
      Potamotrygonidae).
AB  - BACKGROUND: Neotropical freshwater stingrays (Batoidea: Potamotrygonidae) host a
      diverse parasite fauna, including cestodes. Both cestodes and their stingray
      hosts are marine-derived, but the taxonomy of this host/parasite system is poorly
      understood. METHODOLOGY: Morphological and molecular (Cytochrome oxidase I) data
      were used to investigate diversity in freshwater lineages of the cestode genus
      Rhinebothrium Linton, 1890. Results were based on a phylogenetic hypothesis for
      74 COI sequences and morphological analysis of over 400 specimens. Cestodes
      studied were obtained from 888 individual potamotrygonids, representing 14
      recognized and 18 potentially undescribed species from most river systems of
      South America. RESULTS: Morphological species boundaries were based mainly on
      microthrix characters observed with scanning electron microscopy, and were
      supported by COI data. Four species were recognized, including two redescribed
      (Rhinebothrium copianullum and R. paratrygoni), and two newly described (R.
      brooksi n. sp. and R. fulbrighti n. sp.). Rhinebothrium paranaensis Menoret &
      Ivanov, 2009 is considered a junior synonym of R. paratrygoni because the
      morphological features of the two species overlap substantially. The diagnosis of
      Rhinebothrium Linton, 1890 is emended to accommodate the presence of marginal
      longitudinal septa observed in R. copianullum and R. brooksi n. sp. Patterns of
      host specificity and distribution ranged from use of few host species in few
      river basins, to use of as many as eight host species in multiple river basins.
      SIGNIFICANCE: The level of intra-specific morphological variation observed in
      features such as total length and number of proglottids is unparalleled among
      other elasmobranch cestodes. This is attributed to the large representation of
      host and biogeographical samples. It is unclear whether the intra-specific
      morphological variation observed is unique to this freshwater system.
      Nonetheless, caution is urged when using morphological discontinuities to delimit
      elasmobranch cestode species because the amount of variation encountered is
      highly dependent on sample size and/or biogeographical representation.

PMID- 21857938
TI  - Direct response elements of BMP within the PV.1A promoter are essential for its
      transcriptional regulation during early Xenopus development.
AB  - Xvent homeobox genes encode transcription factors that repress organizer genes
      and are essential for dorsoventral specification during early embryogenesis in
      Xenopus. In contrast to the Xvent-2 gene subfamily, Xvent-1 subfamily members,
      including PV.1A, have been proposed as indirect targets of Bone Morphogenetic
      Protein-4 (BMP-4) signaling. Because PV.1A is a critical downstream mediator of,
      and tightly regulated by, BMP-4 signaling, we hypothesized that its promoter
      contains a direct BMP-4 response element to effect this transcriptional
      regulation. We demonstrate that direct regulation by BMP-4 is necessary for
      transcription of PV.1A: its proximal promoter contains cis-acting binding
      elements for Smads and Oaz crucial to induction in response to BMP-4 signaling.
      In addition to these direct cis-acting BMP-4 responsive elements, an indirect
      Xvent-2 response element and several repressive elements exist in the PV.1A
      promoter to regulate its transcription. In summary, PV.1A undergoes combinatorial
      regulation during early Xenopus development as both the direct target of BMP-4
      signaling and as the direct and indirect target of positive and negative
      regulatory factors.

PMID- 21857939
TI  - Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers'
      pneumoconiosis in China: a case-control study.
AB  - BACKGROUND: The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune
      factors and may influence the course of various diseases. In the present study,
      we investigated the association between the potential functional polymorphisms in
      IL-4, IL-4R, and IL-13 and coal workers' pneumoconiosis (CWP) risk in a Chinese
      population. METHODS: Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and
      Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed
      in a case-control study of 556 CWP and 541 control subjects. RESULTS: Our results
      revealed that the IL-4 CT/CC genotypes were associated with a significantly
      decreased risk of CWP (odds ratio (OR) = 0.74, 95% confidence interval (CI) =
      0.58-0.95), compared with the TT genotype, particularly among subgroups of age
      <65 years (OR = 0.68, 95%CI = 0.46-0.99) and dust exposure years >=26 years (OR =
      0.69, 95%CI = 0.50-0.94). Moreover, the polymorphism was significantly associated
      with risk of CWP patients with stage I. In addition, a combined effect was
      observed in a dose-dependent manner with increasing numbers of risk variant
      alleles (P(trend) = 0.023), and individuals with 11-12 risk alleles had a 47%
      higher risk of CWP than those with 0-8 risk alleles (OR = 1.47, 95% CI = 1.05
      2.05). CONCLUSIONS: Our results suggest that the IL-4 C-590T polymorphism is
      involved in the etiology of CWP and susceptibility to this disease. Larger
      studies are warranted to validate our findings.

PMID- 21857940
TI  - Influence of body condition on influenza A virus infection in mallard ducks:
      experimental infection data.
AB  - Migrating waterfowl are implicated in the global spread of influenza A viruses
      (IAVs), and mallards (Anas platyrhynchos) are considered a particularly important
      IAV reservoir. Prevalence of IAV infection in waterfowl peaks during autumn pre
      migration staging and then declines as birds reach wintering areas. Migration is
      energetically costly and birds often experience declines in body condition that
      may suppress immune function. We assessed how body condition affects
      susceptibility to infection, viral shedding and antibody production in wild
      caught and captive-bred juvenile mallards challenged with low pathogenic avian
      influenza virus (LPAIV) H5N9. Wild mallards (n = 30) were separated into three
      experimental groups; each manipulated through food availability to a different
      condition level (-20%, -10%, and normal +/-5% original body condition), and
      captive-bred mallards (n = 10) were maintained at normal condition. We found that
      wild mallards in normal condition were more susceptible to LPAIV infection, shed
      higher peak viral loads and shed viral RNA more frequently compared to birds in
      poor condition. Antibody production did not differ according to condition. We
      found that wild mallards did not differ from captive-bred mallards in viral
      intensity and duration of infection, but they did exhibit lower antibody titers
      and greater variation in viral load. Our findings suggest that reduced body
      condition negatively influences waterfowl host competence to LPAIV infection.
      This observation is contradictory to the recently proposed condition-dependent
      hypothesis, according to which birds in reduced condition would be more
      susceptible to IAV infection. The mechanisms responsible for reducing host
      competency among birds in poor condition remain unknown. Our research indicates
      body condition may influence the maintenance and spread of LPAIV by migrating
      waterfowl.

PMID- 21857941
TI  - The evolution of a female genital trait widely distributed in the Lepidoptera:
      comparative evidence for an effect of sexual coevolution.
AB  - BACKGROUND: Sexual coevolution is considered responsible for the evolution of
      many male genital traits, but its effect on female genital morphology is poorly
      understood. In many lepidopterans, females become temporarily unreceptive after
      mating and the length of this refractory period is inversely related to the
      amount of spermatophore remaining in their genital tracts. Sperm competition can
      select for males that delay female remating by transferring spermatophores with
      thick spermatophore envelopes that take more time to be broken. These envelopes
      could select for signa, sclerotized sharp structures located within the female
      genital tract, that are used for breaking spermatophores. Thus, this hypothesis
      predicts that thick spermatophore envelopes and signa evolve in polyandrous
      species, and that these adaptations are lost when monandry evolves subsequently.
      Here we test the expected associations between female mating pattern and
      presence/absence of signa, and review the scant information available on the
      thickness of spermatophore envelopes. METHODOLOGY/PRINCIPAL FINDINGS: We made a
      literature review and found information on female mating pattern
      (monandry/polyandry), presence/absence of signa and phylogenetic position for 37
      taxa. We built a phylogenetic supertree for these taxa, mapped both traits on it,
      and tested for the predicted association by using Pagel's test for correlated
      evolution. We found that, as predicted by our hypothesis, monandry evolved eight
      times and in five of them signa were lost; preliminary evidence suggests that at
      least in two of the three exceptions males imposed monandry on females by means
      of specially thick spermatophore envelopes. Previously published data on six
      genera of Papilionidae is in agreement with the predicted associations between
      mating pattern and the characteristics of spermatophore envelopes and signa.
      CONCLUSIONS/SIGNIFICANCE: Our results support the hypothesis that signa are a
      product of sexually antagonistic coevolution with spermatophore envelopes.

PMID- 21857942
TI  - Intracellular serine protease inhibitor SERPINB4 inhibits granzyme M-induced cell
      death.
AB  - Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to
      kill virus-infected and tumor cells. In humans, five different granzymes (i.e.
      GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of
      intracellular serine protease inhibitors (serpins) is one of the mechanisms by
      which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular
      expression of SERPINB9 by tumor cells renders them resistant to GrB-induced
      apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors
      are known for the other four human granzymes. In the present study, we show that
      SERPINB4 formed a typical serpin-protease SDS-stable complex with both
      recombinant and native human GrM. Mutation of the P2-P1-P1' triplet in the
      SERPINB4 reactive center loop completely abolished complex formation with GrM and
      N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4
      inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent
      second order rate constant of 1.3*10(4) M(-1) s(-1). SERPINB4 abolished cleavage
      of the macromolecular GrM substrates alpha-tubulin and nucleophosmin.
      Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as
      well as NK cell-mediated cell death and this inhibition depended on the reactive
      center loop of the serpin. As SERPINB4 is highly expressed by squamous cell
      carcinomas, our results may represent a novel mechanism by which these tumor
      cells evade cytotoxic lymphocyte-induced GrM-mediated cell death.

PMID- 21857943
TI  - Voluntary wheel running reverses age-induced changes in hippocampal gene
      expression.
AB  - Normal aging alters expression of numerous genes within the brain. Some of these
      transcription changes likely contribute to age-associated cognitive decline,
      reduced neural plasticity, and the higher incidence of neuropathology.
      Identifying factors that modulate brain aging is crucial for improving quality of
      life. One promising intervention to counteract negative effects of aging is
      aerobic exercise. Aged subjects that exercise show enhanced cognitive performance
      and increased hippocampal neurogenesis and synaptic plasticity. Currently, the
      mechanisms behind the anti-aging effects of exercise are not understood. The
      present study conducted a microarray on whole hippocampal samples from adult (3.5
      month-old) and aged (18-month-old) male BALB/c mice that were individually housed
      with or without running wheels for 8 weeks. Results showed that aging altered
      genes related to chromatin remodeling, cell growth, immune activity, and synapse
      organization compared to adult mice. Exercise was found to modulate many of the
      genes altered by aging, but in the opposite direction. For example, wheel running
      increased expression of genes related to cell growth and attenuated expression of
      genes involved in immune function and chromatin remodeling. Collectively,
      findings show that even late-onset exercise may attenuate age-related changes in
      gene expression and identifies possible pathways through which exercise may exert
      its beneficial effects.

PMID- 21857944
TI  - A double blind, placebo-controlled, randomized crossover study of the acute
      metabolic effects of olanzapine in healthy volunteers.
AB  - BACKGROUND AND RATIONALE: Atypical antipsychotics exhibit metabolic side effects
      including diabetes mellitus and obesity. The adverse events are preceded by acute
      worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty
      acids (FFA) and leptin in animal models. It is unclear whether the same acute
      effects occur in humans. METHODOLOGY/PRINCIPAL FINDINGS: A double blind,
      randomized, placebo-controlled crossover trial was conducted to examine the
      potential metabolic effects of olanzapine in healthy volunteers. Participants
      included male (8) and female (7) subjects [18-30 years old, BMI 18.5-25].
      Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT
      testing. Primary endpoints included measurement of plasma leptin, oral glucose
      tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints
      included: triglycerides, total cholesterol, high- and low-density lipoprotein
      cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine
      increased glucose Area Under the Curve (AUC) by 42% (2808+/-474 vs. 3984+/-444
      mg/dl.min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides
      were elevated 24% (Leptin: 6.8+/-1.3 vs. 8.4+/-1.7 ng/ml; P = 0.0203) and 22%
      (Triglycerides: 88.9+/-10.1 vs. 108.2+/-11.6 mg/dl; P = 0.0170), whereas FFA and
      HDL declined by 32% (FFA: 0.38+/-0.06 vs. 0.26+/-0.04 mM; P = 0.0166) and 11%
      (54.2+/-4.7 vs. 48.9+/-4.3 mg/dl; P = 0.0184), respectively after olanzapine.
      Other measures were unchanged. CONCLUSIONS/SIGNIFICANCE: Olanzapine exerts some
      but not all of the early endocrine/metabolic changes observed in rodent models of
      the metabolic side effects, and this suggest that antipsychotic effects are not
      limited to perturbations in glucose metabolism alone. Future prospective clinical
      studies should focus on identifying which reliable metabolic alterations might be
      useful as potential screening tools in assessing patient susceptibility to weight
      gain and diabetes caused by atypical antipsychotics. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00741026.

PMID- 21857945
TI  - Heaven it's my wife! Male canaries conceal extra-pair courtships but increase
      aggressions when their mate watches.
AB  - Many animals live in a communication network, an environment where individuals
      can obtain information about competitors or potential mates by observing
      interactions between conspecifics. In such an environment, interactants might
      benefit by changing their signalling behaviour in the presence of an audience.
      This audience effect seems widespread among species, has been observed during
      various types of interaction (e.g. intra-sexual vs. inter-sexual interaction) and
      varies according to the social context (e.g. gender, hierarchical or mating
      status of the audience). However, the way individuals might adapt their
      signalling behaviour to a combination of these factors remains poorly understood.
      To address this question, we studied how the presence of an audience affects the
      behaviour of male domestic canaries Serinus canaria during two types of
      interactions: (i) an extra-pair interaction and (ii) a male-male competition for
      food. Males were observed under three conditions: (a) in the absence of audience,
      (b) in the presence of their mate or (c) of a familiar female. Our results show
      that male domestic canaries minutely adapt their courting and agonistic
      behaviours to a combination of: (i) the type of interaction (extra-pair
      interaction/male-male competition), (ii) the social context (mate, familiar
      female or nobody in audience) and (iii) the behaviours of both the audience and
      the interactant. These results highlight the ability of animals to subtly adapt
      their behaviour to the social environment. This also raises questions about the
      cognitive foundations and evolution of these processes especially considering
      that canaries are known neither for having high cognitive abilities nor for being
      a typical example for the social intelligence hypothesis.

PMID- 21857946
TI  - Emergence of bursts and communities in evolving weighted networks.
AB  - Understanding the patterns of human dynamics and social interaction and the way
      they lead to the formation of an organized and functional society are important
      issues especially for techno-social development. Addressing these issues of
      social networks has recently become possible through large scale data analysis of
      mobile phone call records, which has revealed the existence of modular or
      community structure with many links between nodes of the same community and
      relatively few links between nodes of different communities. The weights of
      links, e.g., the number of calls between two users, and the network topology are
      found correlated such that intra-community links are stronger compared to the
      weak inter-community links. This feature is known as Granovetter's "The strength
      of weak ties" hypothesis. In addition to this inhomogeneous community structure,
      the temporal patterns of human dynamics turn out to be inhomogeneous or bursty,
      characterized by the heavy tailed distribution of time interval between two
      consecutive events, i.e., inter-event time. In this paper, we study how the
      community structure and the bursty dynamics emerge together in a simple evolving
      weighted network model. The principal mechanisms behind these patterns are social
      interaction by cyclic closure, i.e., links to friends of friends and the focal
      closure, links to individuals sharing similar attributes or interests, and human
      dynamics by task handling process. These three mechanisms have been implemented
      as a network model with local attachment, global attachment, and priority-based
      queuing processes. By comprehensive numerical simulations we show that the
      interplay of these mechanisms leads to the emergence of heavy tailed inter-event
      time distribution and the evolution of Granovetter-type community structure.
      Moreover, the numerical results are found to be in qualitative agreement with
      empirical analysis results from mobile phone call dataset.

PMID- 21857947
TI  - Gender difference in 2-year mortality and immunological response to ART in an HIV
      infected Chinese population, 2006-2008.
AB  - BACKGROUND: Since it was initiated in 2002, the China Free Antiretroviral
      Treatment (ART) Program has been progressing from an emergency response to a
      standardized treatment and care system. As of December 31, 2009, a total of
      81,880 patients in 31 provinces, autonomous regions, and special municipalities
      received free ART. Gender differences, however, in mortality and immunological
      response to ART in this cohort have never been described. OBJECTIVE: To
      understand whether women and men who enrolled in the China National Free ART
      Program responded equally well to the treatment. METHODS: A retrospective
      analysis of the national free ART databases from June 2006-December 2008 was
      performed. HIV-infected subjects who were 18 years or older, ART naive at
      baseline, and on a 3TC regimen enrolled in the program from June 1 to December
      31, 2006, were included in this study, then followed up to 2 years. RESULTS:
      Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and
      40.8% female. The majority of the subjects were 19-44 years old (77%) and married
      (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in
      males and 11.4% in females (p = 0.0014). Males on therapy for 3-24 months were
      more likely to die than females (HR = 1.46, 95% CI: 1.04-2.06, p = 0.0307) after
      adjusting for baseline characteristics. Compared to men, women had higher CD4+
      counts over time after initiating ART (p<0.0001). CONCLUSIONS: Our study showed
      that women had an overall lower mortality and higher CD4+ counts than men in
      response to ART treatment, which may be attributed to adherence, biological
      factors, social, cultural and economic reasons. Further study is needed to
      explore these factors that might contribute to the gender differences in
      mortality and immunological response to ART.

PMID- 21857948
TI  - Differential effects of prenatal stress in 5-Htt deficient mice: towards
      molecular mechanisms of gene * environment interactions.
AB  - Prenatal stress (PS) has been shown to influence the development of the fetal
      brain and to increase the risk for the development of psychiatric disorders in
      later life. Furthermore, the variation of human serotonin transporter (5-HTT,
      SLC6A4) gene was suggested to exert a modulating effect on the association
      between early life stress and the risk for depression. In the present study, we
      used a 5-Htt*PS paradigm to investigate whether the effects of PS are dependent
      on the 5-Htt genotype. For this purpose, the effects of PS on cognition, anxiety-
      and depression-related behavior were examined using a maternal restraint stress
      paradigm of PS in C57BL6 wild-type (WT) and heterozygous 5-Htt deficient (5-Htt
      +/-) mice. Additionally, in female offspring, a genome-wide hippocampal gene
      expression profiling was performed using the Affymetrix GeneChip(r) Mouse Genome
      430 2.0 Array. 5-Htt +/- offspring showed enhanced memory performance and signs
      of reduced anxiety as compared to WT offspring. In contrast, exposure of 5-Htt +/
      mice to PS was associated with increased depressive-like behavior, an effect
      that tended to be more pronounced in female offspring. Further, 5-Htt genotype,
      PS and their interaction differentially affected the expression of numerous genes
      and related pathways within the female hippocampus. Specifically, MAPK and
      neurotrophin signaling were regulated by both the 5-Htt +/- genotype and PS
      exposure, whereas cytokine and Wnt signaling were affected in a 5-Htt genotype*PS
      manner, indicating a gene*environment interaction at the molecular level. In
      conclusion, our data suggest that although the 5-Htt +/- genotype shows clear
      adaptive capacity, 5-Htt +/- mice--particularly females--at the same time appear
      to be more vulnerable to developmental stress exposure when compared to WT
      offspring. Moreover, hippocampal gene expression profiles suggest that distinct
      molecular mechanisms mediate the behavioral effects of the 5-Htt genotype, PS
      exposure, and their interaction.

PMID- 21857949
TI  - Role of heterozygous APC mutation in niche succession and initiation of
      colorectal cancer--a computational study.
AB  - Mutations in the adenomatous polyposis coli (APC) gene are found in most
      colorectal cancers. They cause constitutive activation of proliferative pathways
      when both alleles of the gene are mutated. However studies on individuals with
      familial adenomatous polyposis (FAP) have shown that a single mutated APC allele
      can also create changes in the precancerous colon crypt, like increased number of
      stem cells, increased crypt fission, greater variability of DNA methylation
      patterns, and higher somatic mutation rates. In this paper, using a computational
      model of colon crypt dynamics, we evolve and investigate a hypothesis on the
      effect of heterozygous APC mutation that explains these different observations.
      Based on previous reports and the results from the computational model we propose
      the hypothesis that heterozygous APC mutation has the effect of increasing the
      chances for a stem cell to divide symmetrically, producing two stem cell
      daughters. We incorporate this hypothesis into the model and perform simulation
      experiments to investigate the consequences of the hypothesis. Simulations show
      that this hypothesis links together the changes in FAP crypts observed in
      previous studies. The simulations also show that an APC(+/-) stem cell gets
      selective advantages for dominating the crypt and progressing to cancer. This
      explains why most colon cancers are initiated by APC mutation. The results could
      have implications for preventing or retarding the onset of colon cancer in people
      with inherited or acquired mutation of one APC allele. Experimental validation of
      the hypothesis as well as investigation into the molecular mechanisms of this
      effect may therefore be worth undertaking.

PMID- 21857950
TI  - Effectiveness of strict vs. multiple use protected areas in reducing tropical
      forest fires: a global analysis using matching methods.
AB  - Protected areas (PAs) cover a quarter of the tropical forest estate. Yet there is
      debate over the effectiveness of PAs in reducing deforestation, especially when
      local people have rights to use the forest. A key analytic problem is the likely
      placement of PAs on marginal lands with low pressure for deforestation, biasing
      comparisons between protected and unprotected areas. Using matching techniques to
      control for this bias, this paper analyzes the global tropical forest biome using
      forest fires as a high resolution proxy for deforestation; disaggregates impacts
      by remoteness, a proxy for deforestation pressure; and compares strictly
      protected vs. multiple use PAs vs indigenous areas. Fire activity was overlaid on
      a 1 km map of tropical forest extent in 2000; land use change was inferred for
      any point experiencing one or more fires. Sampled points in pre-2000 PAs were
      matched with randomly selected never-protected points in the same country.
      Matching criteria included distance to road network, distance to major cities,
      elevation and slope, and rainfall. In Latin America and Asia, strict PAs
      substantially reduced fire incidence, but multi-use PAs were even more effective.
      In Latin America, where there is data on indigenous areas, these areas reduce
      forest fire incidence by 16 percentage points, over two and a half times as much
      as naive (unmatched) comparison with unprotected areas would suggest. In Africa,
      more recently established strict PAs appear to be effective, but multi-use
      tropical forest protected areas yield few sample points, and their impacts are
      not robustly estimated. These results suggest that forest protection can
      contribute both to biodiversity conservation and CO2 mitigation goals, with
      particular relevance to the REDD agenda. Encouragingly, indigenous areas and
      multi-use protected areas can help to accomplish these goals, suggesting some
      compatibility between global environmental goals and support for local
      livelihoods.

PMID- 21857951
TI  - Differences in clinical features according to Boryoung and Karp genotypes of
      Orientia tsutsugamushi.
AB  - BACKGROUND: Scrub typhus is an infectious disease caused by Orientia
      tsutsugamushi. The differences in virulence of O. tsutsugamushi prototypes in
      humans are still unknown. We investigated whether there are any differences in
      the clinical features of the Boryoung and Karp genotypes. METHODOLOGY/PRINCIPAL
      FINDINGS: Patients infected with O. tsutsugamushi, as Boryoung and Karp clusters,
      who had visited 6 different hospitals in southwestern Korea were prospectively
      compared for clinical features, complications, laboratory parameters, and
      treatment responses. Infected patients in the Boryoung cluster had significantly
      more generalized weakness, eschars, skin rashes, conjunctival injection, high
      albumin levels, and greater ESR and fibrinogen levels compared to the Karp
      cluster. The treatment response to current antibiotics was significantly slower
      in the Karp cluster as compared to the Boryoung cluster. CONCLUSION: The
      frequency of occurrence of eschars and rashes may depend on the genotype of O.
      tsutsugamushi.

PMID- 21857952
TI  - HIV and syphilis co-infection increasing among men who have sex with men in
      China: a systematic review and meta-analysis.
AB  - BACKGROUND: This study aims to estimate the magnitude and changing trends of HIV,
      syphilis and HIV-syphilis co-infections among men who have sex with men (MSM) in
      China during 2003-2008 through a systematic review of published literature.
      METHODOLOGY/PRINCIPAL FINDINGS: Chinese and English literatures were searched for
      studies reporting HIV and syphilis prevalence among MSM from 2003 to 2008. The
      prevalence estimates were summarized and analysed by meta-analyses. Meta
      regression was used to identify the potential factors that are associated with
      high heterogeneities in meta-analysis. Seventy-one eligible articles were
      selected in this review (17 in English and 54 in Chinese). Nationally, HIV
      prevalence among MSM increased from 1.3% during 2003-2004 to 2.4% during 2005
      2006 and to 4.7% during 2007-2008. Syphilis prevalence increased from 6.8% during
      2003-2004 to 10.4% during 2005-2006 and to 13.5% during 2007-2008. HIV-syphilis
      co-infection increased from 1.4% during 2005-2006 to 2.7% during 2007-2008. Study
      locations and study period are the two major contributors of heterogeneities of
      both HIV and syphilis prevalence among Chinese MSM. CONCLUSIONS/SIGNIFICANCE:
      There have been significant increases in HIV and syphilis prevalence among MSM in
      China. Scale-up of HIV and syphilis screening and implementation of effective
      public health intervention programs should target MSM to prevent further spread
      of HIV and syphilis infection.

PMID- 21857953
TI  - Increased diacylglycerols characterize hepatic lipid changes in progression of
      human nonalcoholic fatty liver disease; comparison to a murine model.
AB  - BACKGROUND AND AIMS: The spectrum of nonalcoholic fatty liver disease (NAFLD)
      includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to
      cirrhosis. While differences in liver lipids between disease states have been
      reported, precise composition of phospholipids and diacylglycerols (DAG) at a
      lipid species level has not been previously described. The goal of this study was
      to characterize changes in lipid species through progression of human NAFLD using
      advanced lipidomic technology and compare this with a murine model of early and
      advanced NAFLD. METHODS: Utilizing mass spectrometry lipidomics, over 250
      phospholipid and diacylglycerol species (DAGs) were identified in normal and
      diseased human and murine liver extracts. RESULTS: Significant differences
      between phospholipid composition of normal and diseased livers were demonstrated,
      notably among DAG species, consistent with previous reports that DAG transferases
      are involved in the progression of NAFLD and liver fibrosis. In addition, a novel
      phospholipid species (ether linked phosphatidylinositol) was identified in human
      cirrhotic liver extracts. CONCLUSIONS: Using parallel lipidomics analysis of
      murine and human liver tissues it was determined that mice maintained on a high
      fat diet provide a reproducible model of NAFLD in regards to specificity of lipid
      species in the liver. These studies demonstrated that novel lipid species may
      serve as markers of advanced liver disease and importantly, marked increases in
      DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered
      triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels
      characteristic of the disease and specific DAG species might be important lipid
      signaling molecules in the progression of NAFLD.

PMID- 21857954
TI  - The US stock market leads the federal funds rate and treasury bond yields.
AB  - Using a recently introduced method to quantify the time-varying lead-lag
      dependencies between pairs of economic time series (the thermal optimal path
      method), we test two fundamental tenets of the theory of fixed income: (i) the
      stock market variations and the yield changes should be anti-correlated; (ii) the
      change in central bank rates, as a proxy of the monetary policy of the central
      bank, should be a predictor of the future stock market direction. Using both
      monthly and weekly data, we found very similar lead-lag dependence between the
      S&P 500 stock market index and the yields of bonds inside two groups: bond yields
      of short-term maturities (Federal funds rate (FFR), 3M, 6M, 1Y, 2Y, and 3Y) and
      bond yields of long-term maturities (5Y, 7Y, 10Y, and 20Y). In all cases, we
      observe the opposite of (i) and (ii). First, the stock market and yields move in
      the same direction. Second, the stock market leads the yields, including
      especially the FFR. Moreover, we find that the short-term yields in the first
      group lead the long-term yields in the second group before the financial crisis
      that started in mid-2007 and the inverse relationship holds afterwards. These
      results suggest that the Federal Reserve is increasingly mindful of the stock
      market behavior, seen as key to the recovery and health of the economy. Long-term
      investors seem also to have been more reactive and mindful of the signals
      provided by the financial stock markets than the Federal Reserve itself after the
      start of the financial crisis. The lead of the S&P 500 stock market index over
      the bond yields of all maturities is confirmed by the traditional lagged cross
      correlation analysis.

PMID- 21857955
TI  - Feel what you say: an auditory effect on somatosensory perception.
AB  - In the present study, we demonstrate an audiotactile effect in which amplitude
      modulation of auditory feedback during voiced speech induces a throbbing
      sensation over the lip and laryngeal regions. Control tasks coupled with the
      examination of speech acoustic parameters allow us to rule out the possibility
      that the effect may have been due to cognitive factors or motor compensatory
      effects. We interpret the effect as reflecting the tight interplay between
      auditory and tactile modalities during vocal production.

PMID- 21857956
TI  - Mapping salinity tolerance during Arabidopsis thaliana germination and seedling
      growth.
AB  - To characterize and dissect genetic variation for salinity tolerance, we assessed
      variation in salinity tolerance during germination and seedling growth for a
      worldwide sample of Arabidopsis thaliana accessions. By combining QTL mapping,
      association mapping and expression data, we identified genomic regions involved
      in salinity response. Among the worldwide sample, we found germination ability
      within a moderately saline environment (150 mM NaCl) varied considerable, from
      >90% among the most tolerant lines to complete inability to germinate among the
      most susceptible. Our results also demonstrated wide variation in salinity
      tolerance within A. thaliana RIL populations and identified multiple genomic
      regions that contribute to this variation. These regions contain known candidate
      genes, but at least four of the regions contain loci not yet associated with
      salinity tolerance response phenotypes. Our observations suggest A. thaliana
      natural variation may be an underutilized resource for investigating salinity
      stress response.

PMID- 21857957
TI  - Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease
      during experimental autoimmune encephalomyelitis.
AB  - Uncoupling protein 2 is a member of the mitochondrial anion carrier family that
      is widely expressed in neurons and the immune cells of humans. Deletion of Ucp2
      gene in mice pre-activates the immune system leading to higher resistance toward
      infection and to an increased susceptibility to develop chronic inflammatory
      diseases as previously exemplified with the Experimental Autoimmune
      Encephalomyelitis (EAE), a mouse model for multiple sclerosis. Given that
      oxidative stress is enhanced in Ucp2-/- mice and that nitric oxide (NO) also
      plays a critical function in redox balance and in chronic inflammation, we
      generated mice deficient for both Ucp2 and iNos genes and submitted them to EAE.
      Mice lacking iNos gene exhibited the highest clinical score (3.4+/-0.5 p<0.05).
      Surprisingly, mice deficient for both genes developed milder disease with reduced
      immune cell infiltration, cytokines and ROS production as compared to iNos-/-
      mice.

PMID- 21857958
TI  - Molecular analysis of the Retinoic Acid Induced 1 gene (RAI1) in patients with
      suspected Smith-Magenis syndrome without the 17p11.2 deletion.
AB  - Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized
      by multiple congenital anomalies. The syndrome is primarily ascribed to a ~3.7 Mb
      de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes
      likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1)
      is recognized as a major gene involved in the SMS phenotype. Extensive genetic
      and clinical analyses of 36 patients with SMS-like features, but without the
      17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with
      de novo deleterious mutations, and 6 with novel missense variants, 5 of which
      were familial. Haplotype analysis showed two major RAI1 haplotypes in our
      primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred
      haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly
      decreased in cells of patients with the common 17p11.2 deletion, as well as in
      those with de novo RAI1 variants. Expression levels varied in patients with
      familial RAI1 variants and in non-17p11.2 deleted patients without identified
      RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found.
      Two clinical features, ocular abnormalities and polyembolokoilomania (object
      insertion), were significantly correlated with decreased RAI1 expression. While
      not significantly correlated, the presence of hearing loss, seizures, hoarse
      voice, childhood onset of obesity and specific behavioral aspects and the absence
      of immunologic abnormalities and cardiovascular or renal structural anomalies,
      appeared to be specific for the de novo RAI1 subgroup. Recognition of the
      combination of these features will assist in referral for RAI1 analysis of
      patients with SMS-like features without detectable microdeletion of 17p11.2.
      Moreover, RAI1 expression emerged as a genetic target for development of
      therapeutic interventions for SMS.

PMID- 21857959
TI  - High-throughput screening of Australian marine organism extracts for bioactive
      molecules affecting the cellular storage of neutral lipids.
AB  - Mammalian cells store excess fatty acids as neutral lipids in specialised
      organelles called lipid droplets (LDs). Using a simple cell-based assay and open
      source software we established a high throughput screen for LD formation in A431
      cells in order to identify small bioactive molecules affecting lipid storage.
      Screening an n-butanol extract library from Australian marine organisms we
      identified 114 extracts that produced either an increase or a decrease in LD
      formation in fatty acid-treated A431 cells with varying degrees of cytotoxicity.
      We selected for further analysis a non-cytotoxic extract derived from the genus
      Spongia (Heterofibria). Solvent partitioning, HPLC fractionation and
      spectroscopic analysis (NMR, MS) identified a family of related molecules within
      this extract with unique structural features, a subset of which reduced LD
      formation. We selected one of these molecules, heterofibrin A1, for more detailed
      cellular analysis. Inhibition of LD biogenesis by heterofibrin A1 was observed in
      both A431 cells and AML12 hepatocytes. The activity of heterofibrin A1 was dose
      dependent with 20 uM inhibiting LD formation and triglyceride accumulation by
      ~50% in the presence of 50 uM oleic acid. Using a fluorescent fatty acid analogue
      we found that heterofibrin A1 significantly reduces the intracellular
      accumulation of fatty acids and results in the formation of distinct fatty acid
      metabolites in both cultured cells and in embryos of the zebrafish Danio rerio.
      In summary we have shown using readily accessible software and a relatively
      simple assay system that we can identify and isolate bioactive molecules from
      marine extracts, which affect the formation of LDs and the metabolism of fatty
      acids both in vitro and in vivo.

PMID- 21857960
TI  - Characterization of the small RNA transcriptome of the diatom, Thalassiosira
      pseudonana.
AB  - This study presents the first characterization of endogenous small RNAs in a
      diatom, Thalassiosira pseudonana. Small RNAs act as transcriptional and
      translational regulators, controlling specific target genes involved in various
      cellular functions. Diatoms are unicellular photosynthetic organisms that play
      major roles in environmental processes, such as food webs and global carbon
      fixation. Small RNA cDNA libraries were constructed for exponentially growing T.
      pseudonana, and then subjected to highly parallel pyrosequencing (454) and
      sequencing-by-ligation (Applied Biosystems SOLiD). From the computational
      analysis of approximately 300,000 sequences in the 454 library and over 17
      million sequences in the SOLiD libraries, there exists evidence of a core set of
      small RNA genes including: novel microRNAs, repeat-associated short interfering
      RNAs, and endogenous short interfering RNAs. The diatom genome contains elements
      similar to plant small RNA systems, such as the RNAi machinery, a high percentage
      of short interfering RNAs originating from protein-coding and repetitive regions
      of the genome, and putative binding sites of the small RNAs occurring primarily
      in the coding section of the predicted targets. The characterization of the small
      RNA transcriptome of T. pseudonana establishes the possibility of a wide range of
      gene regulatory mechanisms in diatoms.

PMID- 21857961
TI  - Early warning of cotton bollworm resistance associated with intensive planting of
      Bt cotton in China.
AB  - Transgenic crops producing Bacillus thuringiensis (Bt) toxins kill some key
      insect pests, but evolution of resistance by pests can reduce their efficacy. The
      predominant strategy for delaying pest resistance to Bt crops requires refuges of
      non-Bt host plants to promote survival of susceptible pests. To delay pest
      resistance to transgenic cotton producing Bt toxin Cry1Ac, farmers in the United
      States and Australia planted refuges of non-Bt cotton, while farmers in China
      have relied on "natural" refuges of non-Bt host plants other than cotton. Here we
      report data from a 2010 survey showing field-evolved resistance to Cry1Ac of the
      major target pest, cotton bollworm (Helicoverpa armigera), in northern China.
      Laboratory bioassay results show that susceptibility to Cry1Ac was significantly
      lower in 13 field populations from northern China, where Bt cotton has been
      planted intensively, than in two populations from sites in northwestern China
      where exposure to Bt cotton has been limited. Susceptibility to Bt toxin Cry2Ab
      did not differ between northern and northwestern China, demonstrating that
      resistance to Cry1Ac did not cause cross-resistance to Cry2Ab, and implying that
      resistance to Cry1Ac in northern China is a specific adaptation caused by
      exposure to this toxin in Bt cotton. Despite the resistance detected in
      laboratory bioassays, control failures of Bt cotton have not been reported in
      China. This early warning may spur proactive countermeasures, including a switch
      to transgenic cotton producing two or more toxins distinct from Cry1A toxins.

PMID- 21857962
TI  - Quantifying rates of evolutionary adaptation in response to ocean acidification.
AB  - The global acidification of the earth's oceans is predicted to impact
      biodiversity via physiological effects impacting growth, survival, reproduction,
      and immunology, leading to changes in species abundances and global
      distributions. However, the degree to which these changes will play out
      critically depends on the evolutionary rate at which populations will respond to
      natural selection imposed by ocean acidification, which remains largely
      unquantified. Here we measure the potential for an evolutionary response to ocean
      acidification in larval development rate in two coastal invertebrates using a
      full-factorial breeding design. We show that the sea urchin species
      Strongylocentrotus franciscanus has vastly greater levels of phenotypic and
      genetic variation for larval size in future CO(2) conditions compared to the
      mussel species Mytilus trossulus. Using these measures we demonstrate that S.
      franciscanus may have faster evolutionary responses within 50 years of the onset
      of predicted year-2100 CO(2) conditions despite having lower population turnover
      rates. Our comparisons suggest that information on genetic variation, phenotypic
      variation, and key demographic parameters, may lend valuable insight into
      relative evolutionary potentials across a large number of species.

PMID- 21857963
TI  - liver-enriched gene 1a and 1b encode novel secretory proteins essential for
      normal liver development in zebrafish.
AB  - liver-enriched gene 1 (leg1) is a liver-enriched gene in zebrafish and encodes a
      novel protein. Our preliminary data suggested that Leg1 is probably involved in
      early liver development. However, no detailed characterization of Leg1 has been
      reported thus far. We undertook both bioinformatic and experimental approaches to
      study leg1 gene structure and its role in early liver development. We found that
      Leg1 identifies a new conserved protein superfamily featured by the presence of
      domain of unknown function 781 (DUF781). There are two copies of leg1 in
      zebrafish, namely leg1a and leg1b. Both leg1a and leg1b are expressed in the
      larvae and adult liver with leg1a being the predominant form. Knockdown of Leg1a
      or Leg1b by their respective morpholinos specifically targeting their 5'-UTR each
      resulted in a small liver phenotype, demonstrating that both Leg1a and Leg1b are
      important for early liver development. Meanwhile, we found that injection of leg1
      ATG(MO), a morpholino which can simultaneously block the translation of Leg1a and
      Leg1b, caused not only a small liver phenotype but hypoplastic exocrine pancreas
      and intestinal tube as well. Further examination of leg1-ATG(MO) morphants with
      early endoderm markers and early hepatic markers revealed that although depletion
      of total Leg1 does not alter the hepatic and pancreatic fate of the endoderm
      cells, it leads to cell cycle arrest that results in growth retardation of liver,
      exocrine pancreas and intestine. Finally, we proved that Leg1 is a secretory
      protein. This intrigued us to propose that Leg1 might act as a novel secreted
      regulator that is essential for liver and other digestive organ development in
      zebrafish.

PMID- 21857964
TI  - Inability of Prevotella bryantii to form a functional Shine-Dalgarno interaction
      reflects unique evolution of ribosome binding sites in Bacteroidetes.
AB  - The Shine-Dalgarno (SD) sequence is a key element directing the translation to
      initiate at the authentic start codons and also enabling translation initiation
      to proceed in 5' untranslated mRNA regions (5'-UTRs) containing moderately strong
      secondary structures. Bioinformatic analysis of almost forty genomes from the
      major bacterial phylum Bacteroidetes revealed, however, a general absence of SD
      sequence, drop in GC content and consequently reduced tendency to form secondary
      structures in 5'-UTRs. The experiments using the Prevotella bryantii TC1-1
      expression system were in agreement with these findings: neither addition nor
      omission of SD sequence in the unstructured 5'-UTR affected the level of the
      reporter protein, non-specific nuclease NucB. Further, NucB level in P. bryantii
      TC1-1, contrary to hMGFP level in Escherichia coli, was five times lower when SD
      sequence formed part of the secondary structure with a folding energy -5,2
      kcal/mol. Also, the extended SD sequences did not affect protein levels as in E.
      coli. It seems therefore that a functional SD interaction does not take place
      during the translation initiation in P. bryanttii TC1-1 and possibly other
      members of phylum Bacteroidetes although the anti SD sequence is present in 16S
      rRNA genes of their genomes. We thus propose that in the absence of the SD
      sequence interaction, the selection of genuine start codons in Bacteroidetes is
      accomplished by binding of ribosomal protein S1 to unstructured 5'-UTR as opposed
      to coding region which is inaccessible due to mRNA secondary structure.
      Additionally, we found that sequence logos of region preceding the start codons
      may be used as taxonomical markers. Depending on whether complete sequence logo
      or only part of it, such as information content and base proportion at specific
      positions, is used, bacterial genera or families and in some cases even bacterial
      phyla can be distinguished.

PMID- 21857965
TI  - Dietary cholesterol reduces plasma triacylglycerol in apolipoprotein E-null mice:
      suppression of lipin-1 and -2 in the glycerol-3-phosphate pathway.
AB  - BACKGROUND: Cholesterol metabolism is tightly regulated by both cholesterol and
      its metabolites in the mammalian liver, but the regulatory mechanism of
      triacylglycerol (TG) synthesis remains to be elucidated. Lipin, which catalyzes
      the conversion of phosphatidate to diacylglycerol, is a key enzyme involved in de
      novo TG synthesis in the liver via the glycerol-3-phosphate (G3P) pathway.
      However, the regulatory mechanisms for the expression of lipin in the liver are
      not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Apolipoprotein E-knock out
      (apoE-KO) mice were fed a chow supplemented with 1.25% cholesterol (high-Chol
      diet). Cholesterol and bile acids were highly increased in the liver within a
      week. However, the amount of TG in very low-density lipoprotein (VLDL), but not
      in the liver, was reduced by 78%. The epididymal adipose tissue was almost
      eradicated in the long term. DNA microarray and real-time RT-PCR analyses
      revealed that the mRNA expression of all the genes in the G3P pathway in the
      liver was suppressed in the high-Chol diet apoE-KO mice. In particular, the mRNA
      and protein expression of lipin-1 and lipin-2 was markedly decreased, and
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha),
      which up-regulates the transcription of lipin-1, was also suppressed. In vitro
      analysis using HepG2 cells revealed that the protein expression of lipin-2 was
      suppressed by treatment with taurocholic acid. CONCLUSIONS/SIGNIFICANCE: These
      data using apoE-KO mice indicate that cholesterol and its metabolites are
      involved in regulating TG metabolism through a suppression of lipin-1 and lipin-2
      in the liver. This research provides evidence for the mechanism of lipin
      expression in the liver.

PMID- 21857966
TI  - WNT5A signaling contributes to Abeta-induced neuroinflammation and neurotoxicity.
AB  - Neurodegenration is a pathological hallmark of Alzheimer's disease (AD), but the
      underlying molecular mechanism remains elusive. Here, we present evidence that
      reveals a crucial role of Wnt5a signaling in this process. We showed that Wnt5a
      and its receptor Frizzled-5 (Fz5) were up-regulated in the AD mouse brain, and
      that beta-amyloid peptide (Abeta), a major constituent of amyloid plaques,
      stimulated Wnt5a and Fz5 expression in primary cortical cultures; these
      observations indicate that Wnt5a signaling could be aberrantly activated during
      AD pathogenesis. In support of such a possibility, we observed that inhibition of
      Wnt5a signaling attenuated while activation of Wnt5a signaling enhanced Abeta
      evoked neurotoxicity, suggesting a role of Wnt5a signaling in AD-related
      neurodegeneration. Furthermore, we also demonstrated that Abeta-induced
      neurotoxicity depends on inflammatory processes, and that activation of Wnt5a
      signaling elicited the expression of proinflammatory cytokines IL-1beta and TNF
      alpha whereas inhibition of Wnt5a signaling attenuated the Abeta-induced
      expression of the cytokines in cortical cultures. Our findings collectively
      suggest that aberrantly up-regulated Wnt5a signaling is a crucial pathological
      step that contributes to AD-related neurodegeneration by regulating
      neuroinflammation.

PMID- 21857967
TI  - Zebrafish as a potential model organism for drug test against hepatitis C virus.
AB  - Screening and evaluating anti- hepatitis C virus (HCV) drugs in vivo is difficult
      worldwide, mainly because of the lack of suitable small animal models. We
      investigate whether zebrafish could be a model organism for HCV replication. To
      achieve NS5B-dependent replication an HCV sub-replicon was designed and created
      with two vectors, one with HCV ns5b and fluorescent rfp genes, and the other
      containing HCV's 5'UTR, core, 3'UTR and fluorescent gfp genes. The vectors
      containing sub-replicons were co-injected into zebrafish zygotes. The sub
      replicon amplified in liver showing a significant expression of HCV core RNA and
      protein. The sub-replicon amplification caused no abnormality in development and
      growth of zebrafish larvae, but induced gene expression change similar to that in
      human hepatocytes. As the amplified core fluorescence in live zebrafish was
      detectable microscopically, it rendered us an advantage to select those with
      replicating sub-replicon for drug experiments. Ribavirin and oxymatrine, two
      known anti-HCV drugs, inhibited sub-replicon amplification in this model showing
      reduced levels of HCV core RNA and protein. Technically, this method had a good
      reproducibility and is easy to operate. Thus, zebrafish might be a model organism
      to host HCV, and this zebrafish/HCV (sub-replicon) system could be an animal
      model for anti-HCV drug screening and evaluation.

PMID- 21857968
TI  - Role of novelty seeking personality traits as mediator of the association between
      COMT and onset age of drug use in Chinese heroin dependent patients.
AB  - BACKGROUND: Personality traits such as novelty seeking (NS) are associated with
      substance dependence but the mechanism underlying this association remains
      uncertain. Previous studies have focused on the role of the dopamine pathway.
      OBJECTIVE: Examine the relationships between allelic variants of the catechol-O
      methyltransferase (COMT) gene, NS personality traits, and age of onset of drug
      use in heroin-dependent subjects in China. METHODS: The 478 heroin dependent
      subjects from four drug rehabilitation centers in Shanghai who were genotyped for
      eight tagging single nucleotide polymorphisms (SNP) on the COMT gene completed
      the NS subscale from the Temperament and Character Inventory. Multivariate
      analyses were used to assess the potential mediating role of NS personality
      traits in the association between COMT gene variants and the age of onset of
      heroin use. PRINCIPAL FINDINGS AND CONCLUSIONS: In the univariate analysis the
      COMT rs737866 gene variants were independently associated with both NS and age of
      onset of drug use: those with the TT genotype had higher NS subscale scores and
      an earlier onset age of heroin use than individuals with CT or CC genotypes. In
      the multivariate analysis the inclusion of the NS subscore variable weakened the
      relationship between the COMT rs737866 TT genotype and an earlier age of onset of
      drug use. Our findings that COMT is associated with both NS personality traits
      and with the age of onset of heroin use helps to clarify the complex relationship
      between genetic and psychological factors in the development of substance abuse.

PMID- 21857969
TI  - The influence of cognition, anxiety and psychiatric disorders over treatment
      adherence in uncontrolled hypertensive patients.
AB  - BACKGROUND: Poor adherence is estimated to cause 125 thousand deaths per year and
      is linked to 10% of all hospital stays in the U.S. Up to one third of elderly
      hypertensive patients don't have adherence, which is responsible for high
      proportion of hospitalizations. Hypertension is also related to poor performance
      in tests that assess cognitive functions. On the other hand, poor cognitive
      performance is associated with low adherence to treatment. OBJECTIVE: To assess
      the association between cognitive function, anxiety and psychiatric disorders
      with adherence to drug treatment in patients with hypertension. METHODOLOGY AND
      PRINCIPAL FINDINGS: This a cohort studies with 56 adult patients with
      uncontrolled hypertension who participated of all meetings of a pharmaceutical
      intervention in a randomized clinical trial of pharmaceutical care. Cognitive
      function was measured by the Mini Mental State Examination (Mini-mental). The
      memory was measured by digit and word spans, tower and church shadow test, short
      story test and metamemory. Anxiety and psychiatric disorders were evaluated by
      the State Trace Anxiety Inventory and the Self-Report Questionnaire,
      respectively. The participants were classified as adherent or non-adherent to the
      drug treatment, according to the identification of plasma levels of
      hydrochlorothiazide. All non-adherent patients (n = 12) and 35 out 44 (79.5%)
      patients with adherence to treatment had at least one memory test with an altered
      score (P = 0.180). Participants with an unsatisfactory score in the Mini-mental
      had six-fold higher risk of non-adherence to treatment when compared to those
      with a normal score (RR = 5.8; CI 95%: 1.6-20.8; P = 0.007). The scores of
      anxiety and psychiatric disorders were not associated with adherence to the
      pharmacological treatment. CONCLUSION: Cognitive deficit impairs adherence to
      drug therapy and should be screened as part of a program of pharmaceutical care
      to improve adherence to treatment.

PMID- 21857970
TI  - Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through
      inactivation of P300 signaling.
AB  - Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological
      actions including anti-inflammatory and antitumor properties. However, the
      precise action mechanisms of quercetin remain unclear. Here, we reported the
      regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important
      mediator in inflammation and tumor promotion, and revealed the underlying
      mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression
      and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in
      breast cancer cells. Quercetin also significantly inhibited COX-2-mediated
      angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro
      streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation
      assay showed that quercetin considerably inhibited the binding of the
      transactivators CREB2, C-Jun, C/EBPbeta and NF-kappaB and blocked the recruitment
      of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively
      inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the
      p300-mediated acetylation of NF-kappaB. Treatment of cells with p300 HAT
      inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT
      activity. Addition of quercetin to roscovitine-treated cells did not change the
      roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of
      constitutively active p300 significantly reversed the quercetin-mediated
      inhibition of endogenous HAT activity. These results indicate that quercetin
      suppresses COX-2 expression by inhibiting the p300 signaling and blocking the
      binding of multiple transactivators to COX-2 promoter. Our findings therefore
      reveal a novel mechanism of action of quercetin and suggest a potential use for
      quercetin in the treatment of COX-2-mediated diseases such as breast cancers.

PMID- 21857971
TI  - Predicting transcriptional activity of multiple site p53 mutants based on hybrid
      properties.
AB  - As an important tumor suppressor protein, reactivate mutated p53 was found in
      many kinds of human cancers and that restoring active p53 would lead to tumor
      regression. In this work, we developed a new computational method to predict the
      transcriptional activity for one-, two-, three- and four-site p53 mutants,
      respectively. With the approach from the general form of pseudo amino acid
      composition, we used eight types of features to represent the mutation and then
      selected the optimal prediction features based on the maximum relevance, minimum
      redundancy, and incremental feature selection methods. The Mathew's correlation
      coefficients (MCC) obtained by using nearest neighbor algorithm and jackknife
      cross validation for one-, two-, three- and four-site p53 mutants were 0.678,
      0.314, 0.705, and 0.907, respectively. It was revealed by the further optimal
      feature set analysis that the 2D (two-dimensional) structure features composed
      the largest part of the optimal feature set and maybe played the most important
      roles in all four types of p53 mutant active status prediction. It was also
      demonstrated by the optimal feature sets, especially those at the top level, that
      the 3D structure features, conservation, physicochemical and biochemical
      properties of amino acid near the mutation site, also played quite important
      roles for p53 mutant active status prediction. Our study has provided a new and
      promising approach for finding functionally important sites and the relevant
      features for in-depth study of p53 protein and its action mechanism.

PMID- 21857972
TI  - Transcriptome fingerprinting analysis: an approach to explore gene expression
      patterns in marine microbial communities.
AB  - Microbial transcriptomics are providing new insights into the functional
      processes of microbial communities. However, analysis of each sample is still
      expensive and time consuming. A rapid and low cost method that would allow the
      identification of the most interesting samples for posterior in-depth
      metatranscriptomics analysis would be extremely useful. Here we present
      Transcriptome Fingerprinting Analysis (TFA) as an approach to fulfill this
      objective in microbial ecology studies. We have adapted the differential display
      technique for mRNA fingerprinting based on the PCR amplification of expressed
      transcripts to interrogate natural microbial eukaryotic communities. Unlike other
      techniques, TFA does not require prior knowledge of the mRNA sequences to be
      detected. We have used a set of arbitrary primers coupled with a fluorescence
      labeled primer targeting the poly(A) tail of the eukaryotic mRNA, with further
      detection of the resulting labeled cDNA products in an automated genetic
      analyzer. The output represented by electropherogram peak patterns allowed the
      comparison of a set of genes expressed at the time of sampling. TFA has been
      optimized by testing the sensitivity of the method for different initial RNA
      amounts, and the repeatability of the gene expression patterns with increasing
      time after sampling both with cultures and environmental samples. Results show
      that TFA is a promising approach to explore the dynamics of gene expression
      patterns in microbial communities.

PMID- 21857974
TI  - Brain-derived neurotrophic factor in patients with Huntington's disease.
AB  - Reduced Brain-Derived Neurotrophic Factor (BDNF) levels have been described in a
      number of patho-physiological conditions, most notably, in Huntington's disease
      (HD), a progressive neurodegenerative disorder. Since BDNF is also produced in
      blood, we have undertaken the measurement of its peripheral levels in the attempt
      to identify a possible link with HD prognosis and/or its progression. Here we
      evaluated BDNF level in 398 blood samples including 138 controls, 56 preHD, and
      204 HD subjects. We found that BDNF protein levels were not reliably different
      between groups, whether measured in plasma (52 controls, 26 preHD, 105 HD) or
      serum (39 controls, 5 preHD, 29 HD). Our experience, and a re-analysis of the
      literature highlighted that intra-group variability and methodological aspects
      affect this measurement, especially in serum. We also assessed BDNF mRNA levels
      in blood samples from 47 controls, 25 preHD, and 70 HD subjects, and found no
      differences among the groups. We concluded that levels of BDNF in human blood
      were not informative (mRNA levels or plasma protein level) nor reliable (serum
      protein levels) as HD biomarkers. We also wish to warn the scientific community
      in interpreting the significance of changes measured in BDNF protein levels in
      serum from patients suffering from different conditions.

PMID- 21857973
TI  - Drosophila Ten-m and filamin affect motor neuron growth cone guidance.
AB  - The Drosophila Ten-m (also called Tenascin-major, or odd Oz (odz)) gene has been
      associated with a pair-rule phenotype. We identified and characterized new
      alleles of Drosophila Ten-m to establish that this gene is not responsible for
      segmentation defects but rather causes defects in motor neuron axon routing. In
      Ten-m mutants the inter-segmental nerve (ISN) often crosses segment boundaries
      and fasciculates with the ISN in the adjacent segment. Ten-m is expressed in the
      central nervous system and epidermal stripes during the stages when the growth
      cones of the neurons that form the ISN navigate to their targets. Over-expression
      of Ten-m in epidermal cells also leads to ISN misrouting. We also found that
      Filamin, an actin binding protein, physically interacts with the Ten-m protein.
      Mutations in cheerio, which encodes Filamin, cause defects in motor neuron axon
      routing like those of Ten-m. During embryonic development, the expression of
      Filamin and Ten-m partially overlap in ectodermal cells. These results suggest
      that Ten-m and Filamin in epidermal cells might together influence growth cone
      progression.

PMID- 21857975
TI  - Watershed urbanization alters the composition and function of stream bacterial
      communities.
AB  - Watershed urbanization leads to dramatic changes in draining streams, with urban
      streams receiving a high frequency of scouring flows, together with the nutrient,
      contaminant, and thermal pollution associated with urbanization. These changes
      are known to cause significant losses of sensitive insect and fish species from
      urban streams, yet little is known about how these changes affect the composition
      and function of stream microbial communities. Over the course of two years, we
      repeatedly sampled sediments from eight central North Carolina streams affected
      to varying degrees by watershed urbanization. For each stream and sampling date,
      we characterized both overall and denitrifying bacterial communities and measured
      denitrification potentials. Denitrification is an ecologically important process,
      mediated by denitrifying bacteria that use nitrate and organic carbon as
      substrates. Differences in overall and denitrifying bacterial community
      composition were strongly associated with the gradient in urbanization.
      Denitrification potentials, which varied widely, were not significantly
      associated with substrate supply. By incorporating information on the community
      composition of denitrifying bacteria together with substrate supply in a linear
      mixed-effects model, we explained 45% of the variation in denitrification
      potential (p-value<0.001). Our results suggest that (1) the composition of stream
      bacterial communities change in response to watershed urbanization and (2) such
      changes may have important consequences for critical ecosystem functions such as
      denitrification.

PMID- 21857976
TI  - Plasma miRNA as biomarkers for assessment of total-body radiation exposure
      dosimetry.
AB  - The risk of radiation exposure, due to accidental or malicious release of
      ionizing radiation, is a major public health concern. Biomarkers that can rapidly
      identify severely-irradiated individuals requiring prompt medical treatment in
      mass-casualty incidents are urgently needed. Stable blood or plasma-based
      biomarkers are attractive because of the ease for sample collection. We tested
      the hypothesis that plasma miRNA expression profiles can accurately reflect prior
      radiation exposure. We demonstrated using a murine model that plasma miRNA
      expression signatures could distinguish mice that received total body irradiation
      doses of 0.5 Gy, 2 Gy, and 10 Gy (at 6 h or 24 h post radiation) with accuracy,
      sensitivity, and specificity of above 90%. Taken together, these data demonstrate
      that plasma miRNA profiles can be highly predictive of different levels of
      radiation exposure. Thus, plasma-based biomarkers can be used to assess radiation
      exposure after mass-casualty incidents, and it may provide a valuable tool in
      developing and implementing effective countermeasures.

PMID- 21857977
TI  - Structural basis for species specific inhibition of 17beta-hydroxysteroid
      dehydrogenase type 1 (17beta-HSD1): computational study and biological
      validation.
AB  - 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyzes the reduction
      of estrone to estradiol, which is the most potent estrogen in humans. Inhibition
      of 17beta-HSD1 and thereby reducing the intracellular estradiol concentration is
      thus a promising approach for the treatment of estrogen dependent diseases. In
      the past, several steroidal and non-steroidal inhibitors of 17beta-HSD1 have been
      described but so far there is no cocrystal structure of the latter in complex
      with 17beta-HSD1. However, a distinct knowledge of active site topologies and
      protein-ligand interactions is a prerequisite for structure-based drug design and
      optimization. An elegant strategy to enhance this knowledge is to compare
      inhibition values obtained for one compound toward ortholog proteins from various
      species, which are highly conserved in sequence and differ only in few residues.
      In this study the inhibitory potencies of selected members of different non
      steroidal inhibitor classes toward marmoset 17beta-HSD1 were determined and the
      data were compared with the values obtained for the human enzyme. A species
      specific inhibition profile was observed in the class of the
      (hydroxyphenyl)naphthols. Using a combination of computational methods, including
      homology modelling, molecular docking, MD simulation, and binding energy
      calculation, a reasonable model of the three-dimensional structure of marmoset
      17beta-HSD1 was developed and inhibition data were rationalized on the structural
      basis. In marmoset 17beta-HSD1, residues 190 to 196 form a small alpha-helix,
      which induces conformational changes compared to the human enzyme. The docking
      poses suggest these conformational changes as determinants for species
      specificity and energy decomposition analysis highlighted the outstanding role of
      Asn152 as interaction partner for inhibitor binding. In summary, this strategy of
      comparing the biological activities of inhibitors toward highly conserved
      ortholog proteins might be an alternative to laborious x-ray or site-directed
      mutagenesis experiments in certain cases. Additionally, it facilitates inhibitor
      design and optimization by offering new information on protein-ligand
      interactions.

PMID- 21857978
TI  - Modeling peripheral olfactory coding in Drosophila larvae.
AB  - The Drosophila larva possesses just 21 unique and identifiable pairs of olfactory
      sensory neurons (OSNs), enabling investigation of the contribution of individual
      OSN classes to the peripheral olfactory code. We combined electrophysiological
      and computational modeling to explore the nature of the peripheral olfactory code
      in situ. We recorded firing responses of 19/21 OSNs to a panel of 19 odors. This
      was achieved by creating larvae expressing just one functioning class of odorant
      receptor, and hence OSN. Odor response profiles of each OSN class were highly
      specific and unique. However many OSN-odor pairs yielded variable responses, some
      of which were statistically indistinguishable from background activity. We used
      these electrophysiological data, incorporating both responses and spontaneous
      firing activity, to develop a bayesian decoding model of olfactory processing.
      The model was able to accurately predict odor identity from raw OSN responses;
      prediction accuracy ranged from 12%-77% (mean for all odors 45.2%) but was always
      significantly above chance (5.6%). However, there was no correlation between
      prediction accuracy for a given odor and the strength of responses of wild-type
      larvae to the same odor in a behavioral assay. We also used the model to predict
      the ability of the code to discriminate between pairs of odors. Some of these
      predictions were supported in a behavioral discrimination (masking) assay but
      others were not. We conclude that our model of the peripheral code represents
      basic features of odor detection and discrimination, yielding insights into the
      information available to higher processing structures in the brain.

PMID- 21857979
TI  - Successful control of methicillin-resistant Staphylococcus aureus in endemic
      neonatal intensive care units--a 7-year campaign.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most
      important nosocomial pathogens in the intensive care unit (ICU) worldwide,
      including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for
      MRSA. METHODOLOGY/PRINCIPAL FINDINGS: To control MRSA spread in our NICUs, we
      implemented a series of infection control measures stepwise, including
      reinforcement of hand hygiene since January 2000, augmentation of aseptic care
      over the insertion site of central venous catheter since July 2001, introduction
      of alcohol-based handrubs since April 2003, surveillance culture for MRSA and
      cohort care for the colonized patients between March 2003 and February 2004, and
      surveillance culture with subsequent decolonization of MRSA between August 2005
      and July 2006. After implementation of these measures, MRSA healthcare-associated
      infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days
      in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream
      infection reduced from 40 cases in 1999 to only one case in 2006. Compared to
      those obtained during the period of surveillance culture without decolonization,
      both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs.
      12%, p<0.001) decreased significantly during the period of surveillance and
      decolonization. Molecular analysis of the clinical isolates during the study
      period showed that the endemic clone, which dominated between 1998 and 2005,
      almost disappeared in 2006, while the community clones increased significantly in
      2006-2007. CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs
      can be successfully controlled, even in areas with high levels of endemic MRSA
      infections such as our NICUs.

PMID- 21857980
TI  - Diversification and molecular evolution of ATOH8, a gene encoding a bHLH
      transcription factor.
AB  - ATOH8 is a bHLH domain transcription factor implicated in the development of the
      nervous system, kidney, pancreas, retina and muscle. In the present study, we
      collected sequence of ATOH8 orthologues from 18 vertebrate species and 24
      invertebrate species. The reconstruction of ATOH8 phylogeny and sequence analysis
      showed that this gene underwent notable divergences during evolution. For those
      vertebrate species investigated, we analyzed the gene structure and regulatory
      elements of ATOH8. We found that the bHLH domain of vertebrate ATOH8 was highly
      conserved. Mammals retained some specific amino acids in contrast to the non
      mammalian orthologues. Mammals also developed another potential isoform, verified
      by a human expressed sequence tag (EST). Comparative genomic analyses of the
      regulatory elements revealed a replacement of the ancestral TATA box by CpG
      islands in the eutherian mammals and an evolutionary tendency for TATA box
      reduction in vertebrates in general. We furthermore identified the region of the
      effective promoter of human ATOH8 which could drive the expression of EGFP
      reporter in the chicken embryo. In the opossum, both the coding region and
      regulatory elements of ATOH8 have some special features, such as the unique
      extended C-terminus encoded by the third exon and absence of both CpG islands and
      TATA elements in the regulatory region. Our gene mapping data showed that in
      human, ATOH8 was hosted in one chromosome which is a fusion product of two
      orthologous chromosomes in non-human primates. This unique chromosomal
      environment of human ATOH8 probably subjects its expression to the regulation at
      chromosomal level. We deduce that the great interspecific differences found in
      both ATOH8 gene sequence and its regulatory elements might be significant for the
      fine regulation of its spatiotemporal expression and roles of ATOH8, thus
      orchestrating its function in different tissues and organisms.

PMID- 21857981
TI  - The complete mitochondrial genome of the Asiatic cavity-nesting honeybee Apis
      cerana (Hymenoptera: Apidae).
AB  - In the present study, we determined the complete mitochondrial DNA (mtDNA)
      sequence of Apis cerana, the Asiatic cavity-nesting honeybee. We present here an
      analysis of features of its gene content and genome organization in comparison
      with Apis mellifera to assess the variation within the genus Apis and among main
      groups of Hymenoptera. The size of the entire mt genome of A. cerana is 15,895
      bp, containing 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA
      (tRNA) genes and one control region. These genes are transcribed from both
      strands and have a nucleotide composition high in A and T. The contents of A+T of
      the complete genomes are 83.96% for A. cerana. The AT bias had a significant
      effect on both the codon usage pattern and amino acid composition of proteins.
      There are a total of 3672 codons in all 13 protein-coding genes, excluding
      termination codons. The most frequently used amino acid is Leu (15.52%), followed
      by Ile (12.85%), Phe (10.10%), Ser (9.15%) and Met (8.96%). Intergenic regions in
      the mt genome of A. cerana are 705 bp in total. The order and orientation of the
      gene arrangement pattern is identical to that of A. mellifera, except for the
      position of the tRNA-Ser(AGN) gene. Phylogenetic analyses using concatenated
      amino acid sequences of 13 protein-coding genes, with three different
      computational algorithms (NJ, MP and ML), all revealed two distinct groups with
      high statistical support, indicating that A. cerana and A. mellifera are two
      separate species, consistent with results of previous morphological and molecular
      studies. The complete mtDNA sequence of A. cerana provides additional genetic
      markers for studying population genetics, systematics and phylogeographics of
      honeybees.

PMID- 21857982
TI  - Wnt/beta-catenin signalling is active in a highly dynamic pattern during
      development of the mouse cerebellum.
AB  - The adult cerebellum is composed of several distinct cell types with well defined
      developmental origins. However, the molecular mechanisms that govern the
      generation of these cell types are only partially resolved. Wnt/beta-catenin
      signalling has a wide variety of roles in generation of the central nervous
      system, though the specific activity of this pathway during cerebellum
      development is not well understood. Here, we present data that delineate the
      spatio-temporal specific pattern of Wnt/beta-catenin signaling during mouse
      cerebellum development between E12.5 and P21. Using the BAT-gal Wnt/beta-catenin
      reporter mouse, we found that Wnt/beta-catenin activity is present transiently at
      the embryonic rhombic lip but not at later stages during the expansion of cell
      populations that arise from there. At late embryonic and early postnatal stages,
      Wnt/beta-catenin activity shifts to the cerebellar ventricular zone and to cells
      arising from this germinal centre. Subsequently, the expression pattern becomes
      progressively restricted to Bergmann glial cells, which show expression of the
      reporter at P21. These results indicate a variety of potential functions for
      Wnt/beta-catenin activity during cerebellum development.

PMID- 21857983
TI  - Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy.
AB  - Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously
      euploid. Here we report that normal hPSC--including induced pluripotent--lines
      are karyotypic mosaics of euploid cells intermixed with many cells showing non
      clonal aneuploidies as identified by chromosome counting, spectral karyotyping
      (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic
      cells. This mosaic aneuploidy resembles that observed in progenitor cells of the
      developing brain and preimplantation embryos, suggesting that it is a normal,
      rather than pathological, feature of stem cell lines. The karyotypic
      heterogeneity generated by mosaic aneuploidy may contribute to the reported
      functional and phenotypic heterogeneity of hPSCs lines, as well as their
      therapeutic efficacy and safety following transplantation.

PMID- 21857984
TI  - Allelic heterogeneity and genetic modifier loci contribute to clinical variation
      in males with X-linked retinitis pigmentosa due to RPGR mutations.
AB  - Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP),
      characterized by retinal degeneration and eventual blindness. The clinical
      consequences of RPGR mutations are highly varied, even among individuals with the
      same mutation: males demonstrate a wide range of clinical severity, and female
      carriers may or may not be affected. This study describes the phenotypic
      diversity in a cohort of 98 affected males from 56 families with RPGR mutations,
      and demonstrates the contribution of genetic factors (i.e., allelic heterogeneity
      and genetic modifiers) to this diversity. Patients were categorized as grade 1
      (mild), 2 (moderate) or 3 (severe) according to specific clinical criteria.
      Patient DNAs were genotyped for coding SNPs in 4 candidate modifier genes with
      products known to interact with RPGR protein: RPGRIP1, RPGRIP1L, CEP290, and
      IQCB1. Family-based association testing was performed using PLINK. A wide range
      of clinical severity was observed both between and within families. Patients with
      mutations in exons 1-14 were more severely affected than those with ORF15
      mutations, and patients with predicted null alleles were more severely affected
      than those predicted to make RPGR protein. Two SNPs showed association with
      severe disease: the minor allele (N) of I393N in IQCB1 (p = 0.044) and the common
      allele (R) of R744Q in RPGRIP1L (p = 0.049). These data demonstrate that allelic
      heterogeneity contributes to phenotypic diversity in XlRP and suggest that this
      may depend on the presence or absence of RPGR protein. In addition, common
      variants in 2 proteins known to interact with RPGR are associated with severe
      disease in this cohort.

PMID- 21857985
TI  - Chronic myeloid leukemia patients in prolonged remission following interferon
      alpha monotherapy have distinct cytokine and oligoclonal lymphocyte profile.
AB  - Before the era of tyrosine kinase inhibitors (TKIs), interferon-alpha (IFN-alpha)
      was the treatment of choice in chronic myeloid leukemia (CML). Curiously, some
      IFN-alpha treated patients were able to discontinue therapy without disease
      progression. The aim of this project was to study the immunomodulatory effects of
      IFN-alpha in CML patients in prolonged remission and isolate biological markers
      predicting response. Due to rarity of patients on IFN-alpha monotherapy, a
      relatively small cohort of patients still on treatment (IFN-ON, n = 10, median
      therapy duration 11.8 years) or had discontinued IFN-alpha therapy but remained
      in remission for >2 years (IFN-OFF, n = 9) were studied. The lymphocyte
      immunophenotype was analyzed with a comprehensive flow cytometry panel and plasma
      cytokine levels were measured with multiplex bead-based assay. In addition, the
      clonality status of different lymphocyte subpopulations was analyzed by TCR
      gamma/delta rearrangement assay. Median NK-cell absolute number and proportion
      from lymphocytes in blood was higher in IFN-OFF patients as compared to IFN-ON
      patients or controls (0.42, 0.19, 0.21*10(9)/L; 26%, 12%, 11%, respectively,
      p<0.001). The proportion of CD8+ T-cells was significantly increased in both
      patient groups and a larger proportion of T-cells expressed CD45RO. Most (95%)
      patients had significant numbers of oligoclonal lymphocytes characterized by T
      cell receptor gamma/delta rearrangements. Strikingly, in the majority of patients
      (79%) a distinct clonal Vgamma9 gene rearrangement was observed residing in
      gammadelta(+) T-cell population. Similar unique clonality pattern was not
      observed in TKI treated CML patients. Plasma eotaxin and MCP-1 cytokines were
      significantly increased in IFN-OFF patients. Despite the limited number of
      patients, our data indicates that IFN-alpha treated CML patients in remission
      have increased numbers of NK-cells and clonal gammadelta(+) T-cells and a unique
      plasma cytokine profile. These factors may relate to anti-leukemic effects of IFN
      alpha in this specific group of patients and account for prolonged therapy
      responses even after drug discontinuation.

PMID- 21857986
TI  - Vesicular stomatitis virus infection promotes immune evasion by preventing NKG2D
      ligand surface expression.
AB  - Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic
      ability in cancer treatment. Initially, we hypothesized that VSV infection could
      increase immune recognition of cancer cells through induction of the immune
      stimulatory NKG2D-ligands. Here we show that VSV infection leads to a robust
      induction of MICA mRNA expression, however the subsequent surface expression is
      potently hindered. Thus, VSV lines up with human cytomegalovirus (HCMV) and
      adenovirus, which actively subvert the immune system by negatively affecting
      NKG2D-ligand surface expression. VSV infection caused an active suppression of
      NKG2D-ligand surface expression, affecting both endogenous and histone
      deacetylase (HDAC)-inhibitor induced MICA, MICB and ULBP-2 expression. The
      classical immune escape mechanism of VSV (i.e., the M protein blockade of
      nucleocytoplasmic mRNA transport) was not involved, as the VSV mutant strain,
      VSV(DeltaM51), which possess a defective M protein, prevented MICA surface
      expression similarly to wild-type VSV. The VSV mediated down modulation of NKG2D
      ligand expression did not involve apoptosis. Constitutive expression of MICA
      bypassed the escape mechanism, suggesting that VSV affect NKG2D-ligand expression
      at an early post-transcriptional level. Our results show that VSV possess an
      escape mechanism, which could affect the immune recognition of VSV infected
      cancer cells. This may also have implications for immune recognition of cancer
      cells after combined treatment with VSV and chemotherapeutic drugs.

PMID- 21857987
TI  - A crystal structure of the catalytic core domain of an avian sarcoma and leukemia
      virus integrase suggests an alternate dimeric assembly.
AB  - Integrase (IN) is an important therapeutic target in the search for anti-Human
      Immunodeficiency Virus (HIV) inhibitors. This enzyme is composed of three domains
      and is hard to crystallize in its full form. First structural results on IN were
      obtained on the catalytic core domain (CCD) of the avian Rous and Sarcoma Virus
      strain Schmidt-Ruppin A (RSV-A) and on the CCD of HIV-1 IN. A ribonuclease-H like
      motif was revealed as well as a dimeric interface stabilized by two pairs of
      alpha-helices (alpha1/alpha5, alpha5/alpha1). These structural features have been
      validated in other structures of IN CCDs. We have determined the crystal
      structure of the Rous-associated virus type-1 (RAV-1) IN CCD to 1.8 A resolution.
      RAV-1 IN shows a standard activity for integration and its CCD differs in
      sequence from that of RSV-A by a single accessible residue in position 182
      (substitution A182T). Surprisingly, the CCD of RAV-1 IN associates itself with an
      unexpected dimeric interface characterized by three pairs of alpha-helices
      (alpha3/alpha5, alpha1/alpha1, alpha5/alpha3). A182 is not involved in this novel
      interface, which results from a rigid body rearrangement of the protein at its
      alpha1, alpha3, alpha5 surface. A new basic groove that is suitable for single
      stranded nucleic acid binding is observed at the surface of the dimer. We have
      subsequently determined the structure of the mutant A182T of RAV-1 IN CCD and
      obtained a RSV-A IN CCD-like structure with two pairs of buried alpha-helices at
      the interface. Our results suggest that the CCD of avian INs can dimerize in more
      than one state. Such flexibility can further explain the multifunctionality of
      retroviral INs, which beside integration of dsDNA are implicated in different
      steps of the retroviral cycle in presence of viral ssRNA.

PMID- 21857988
TI  - The stromal processing peptidase of chloroplasts is essential in Arabidopsis,
      with knockout mutations causing embryo arrest after the 16-cell stage.
AB  - Stromal processing peptidase (SPP) is a metalloendopeptidase located in the
      stroma of chloroplasts, and it is responsible for the cleavage of transit
      peptides from preproteins upon their import into the organelle. Two independent
      mutant Arabidopsis lines with T-DNA insertions in the SPP gene were analysed (spp
      1 and spp-2). For both lines, no homozygous mutant plants could be detected, and
      the segregating progeny of spp heterozygotes contained heterozygous and wild-type
      plants in a ratio of 2?1. The siliques of heterozygous spp-1 and spp-2 plants
      contained many aborted seeds, at a frequency of ~25%, suggesting embryo
      lethality. By contrast, transmission of the spp mutations through the male and
      female gametes was found to be normal, and so gametophytic effects could be ruled
      out. To further elucidate the timing of the developmental arrest, mutant and wild
      type seeds were cleared and analysed by Nomarski microscopy. A significant
      proportion (~25%) of the seeds in mutant siliques exhibited delayed embryogenesis
      compared to those in wild type. Moreover, the mutant embryos never progressed
      normally beyond the 16-cell stage, with cell divisions not completing properly
      thereafter. Heterozygous spp mutant plants were phenotypically indistinguishable
      from the wild type, indicating that the spp knockout mutations are completely
      recessive and suggesting that one copy of the SPP gene is able to produce
      sufficient SPP protein for normal development under standard growth conditions.

PMID- 21857989
TI  - Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma
      cruzi.
AB  - BACKGROUND: The Trypanosoma cruzi genome was sequenced from a hybrid strain (CL
      Brener). However, high allelic variation and the repetitive nature of the genome
      have prevented the complete linear sequence of chromosomes being determined.
      Determining the full complement of chromosomes and establishing syntenic groups
      will be important in defining the structure of T. cruzi chromosomes. A large
      amount of information is now available for T. cruzi and Trypanosoma brucei,
      providing the opportunity to compare and describe the overall patterns of
      chromosomal evolution in these parasites. METHODOLOGY/PRINCIPAL FINDINGS: The
      genome sizes, repetitive DNA contents, and the numbers and sizes of chromosomes
      of nine strains of T. cruzi from four lineages (TcI, TcII, TcV and TcVI) were
      determined. The genome of the TcI group was statistically smaller than other
      lineages, with the exception of the TcI isolate Tc1161 (Jose-IMT). Satellite DNA
      content was correlated with genome size for all isolates, but this was not
      accompanied by simultaneous amplification of retrotransposons. Regardless of
      chromosomal polymorphism, large syntenic groups are conserved among T. cruzi
      lineages. Duplicated chromosome-sized regions were identified and could be
      retained as paralogous loci, increasing the dosage of several genes. By comparing
      T. cruzi and T. brucei chromosomes, homologous chromosomal regions in T. brucei
      were identified. Chromosomes Tb9 and Tb11 of T. brucei share regions of syntenic
      homology with three and six T. cruzi chromosomal bands, respectively.
      CONCLUSIONS: Despite genome size variation and karyotype polymorphism, T. cruzi
      lineages exhibit conservation of chromosome structure. Several syntenic groups
      are conserved among all isolates analyzed in this study. The syntenic regions are
      larger than expected if rearrangements occur randomly, suggesting that they are
      conserved owing to positive selection. Mapping of the syntenic regions on T.
      cruzi chromosomal bands provides evidence for the occurrence of fusion and split
      events involving T. brucei and T. cruzi chromosomes.

PMID- 21857990
TI  - The accuracy of the electrocardiogram during exercise stress test based on heart
      size.
AB  - BACKGROUND: Multiple studies have shown that the exercise electrocardiogram (ECG)
      is less accurate for predicting ischemia, especially in women, and there is
      additional evidence to suggest that heart size may affect its diagnostic
      accuracy. HYPOTHESIS: The purpose of this investigation was to assess the
      diagnostic accuracy of the exercise ECG based on heart size. METHODS: We
      evaluated 1,011 consecutive patients who were referred for an exercise nuclear
      stress test. Patients were divided into two groups: small heart size defined as
      left ventricular end diastolic volume (LVEDV) <65 mL (Group A) and normal heart
      size defined as LVEDV >=65 mL (Group B) and associations between ECG outcome
      (false positive vs. no false positive) and heart size (small vs. normal) were
      analyzed using the Chi square test for independence, with a Yates continuity
      correction. LVEDV calculations were performed via a computer-processing
      algorithm. SPECT myocardial perfusion imaging was used as the gold standard for
      the presence of coronary artery disease (CAD). RESULTS: Small heart size was
      found in 142 patients, 123 female and 19 male patients. There was a significant
      association between ECG outcome and heart size (chi(2) = 4.7, p = 0.03), where
      smaller hearts were associated with a significantly greater number of false
      positives. CONCLUSIONS: This study suggests a possible explanation for the poor
      diagnostic accuracy of exercise stress testing, especially in women, as the
      overwhelming majority of patients with small heart size were women.

PMID- 21857992
TI  - Larval transport modeling of deep-sea invertebrates can aid the search for
      undiscovered populations.
AB  - BACKGROUND: Many deep-sea benthic animals occur in patchy distributions separated
      by thousands of kilometres, yet because deep-sea habitats are remote, little is
      known about their larval dispersal. Our novel method simulates dispersal by
      combining data from the Argo array of autonomous oceanographic probes, deep-sea
      ecological surveys, and comparative invertebrate physiology. The predicted
      particle tracks allow quantitative, testable predictions about the dispersal of
      benthic invertebrate larvae in the south-west Pacific. PRINCIPAL FINDINGS: In a
      test case presented here, using non-feeding, non-swimming (lecithotrophic
      trochophore) larvae of polyplacophoran molluscs (chitons), we show that the
      likely dispersal pathways in a single generation are significantly shorter than
      the distances between the three known population centres in our study region. The
      large-scale density of chiton populations throughout our study region is
      potentially much greater than present survey data suggest, with intermediate
      'stepping stone' populations yet to be discovered. CONCLUSIONS/SIGNIFICANCE: We
      present a new method that is broadly applicable to studies of the dispersal of
      deep-sea organisms. This test case demonstrates the power and potential
      applications of our new method, in generating quantitative, testable hypotheses
      at multiple levels to solve the mismatch between observed and expected
      distributions: probabilistic predictions of locations of intermediate
      populations, potential alternative dispersal mechanisms, and expected population
      genetic structure. The global Argo data have never previously been used to
      address benthic biology, and our method can be applied to any non-swimming larvae
      of the deep-sea, giving information upon dispersal corridors and population
      densities in habitats that remain intrinsically difficult to assess.

PMID- 21857991
TI  - ATR-p53 restricts homologous recombination in response to replicative stress but
      does not limit DNA interstrand crosslink repair in lung cancer cells.
AB  - Homologous recombination (HR) is required for the restart of collapsed DNA
      replication forks and error-free repair of DNA double-strand breaks (DSB).
      However, unscheduled or hyperactive HR may lead to genomic instability and
      promote cancer development. The cellular factors that restrict HR processes in
      mammalian cells are only beginning to be elucidated. The tumor suppressor p53 has
      been implicated in the suppression of HR though it has remained unclear why p53,
      as the guardian of the genome, would impair an error-free repair process. Here,
      we show for the first time that p53 downregulates foci formation of the RAD51
      recombinase in response to replicative stress in H1299 lung cancer cells in a
      manner that is independent of its role as a transcription factor. We find that
      this downregulation of HR is not only completely dependent on the binding site of
      p53 with replication protein A but also the ATR/ATM serine 15 phosphorylation
      site. Genetic analysis suggests that ATR but not ATM kinase modulates p53's
      function in HR. The suppression of HR by p53 can be bypassed under experimental
      conditions that cause DSB either directly or indirectly, in line with p53's role
      as a guardian of the genome. As a result, transactivation-inactive p53 does not
      compromise the resistance of H1299 cells to the interstrand crosslinking agent
      mitomycin C. Altogether, our data support a model in which p53 plays an anti
      recombinogenic role in the ATR-dependent mammalian replication checkpoint but
      does not impair a cell's ability to use HR for the removal of DSB induced by
      cytotoxic agents.

PMID- 21857993
TI  - Susceptibility to predation affects trait-mediated indirect interactions by
      reversing interspecific competition.
AB  - Numerous studies indicate that the behavioral responses of prey to the presence
      of predators can have an important role in structuring assemblages through trait
      mediated indirect interactions. Few studies, however, have addressed how relative
      susceptibility to predation influences such interactions. Here we examine the
      effect of chemical cues from the common shore crab Carcinus maenas on the
      foraging behavior of two common intertidal gastropod molluscs. Of the two model
      consumers studied, Littorina littorea is morphologically more vulnerable to crab
      predation than Gibbula umbilicalis, and it exhibited greater competitive ability
      in the absence of predation threat. However, Littorina demonstrated a greater
      anti-predator response when experimentally exposed to predation cues, resulting
      in a lower level of foraging. This reversed the competitive interaction, allowing
      Gibbula substantially increased access to shared resources. Our results
      demonstrate that the susceptibility of consumers to predation can influence
      species interactions, and suggest that inter-specific differences in trait
      mediated indirect interactions are another mechanism through which non
      consumptive predator effects may influence trophic interactions.

PMID- 21857994
TI  - Subunit interface residues F129 and H294 of human RAD51 are essential for
      recombinase function.
AB  - RAD51 mediated homologous recombinational repair (HRR) of DNA double-strand
      breaks (DSBs) is essential to maintain genomic integrity. RAD51 forms a
      nucleoprotein filament (NPF) that catalyzes the fundamental homologous pairing
      and strand exchange reaction (recombinase) required for HRR. Based on structural
      and functional homology with archaeal and yeast RAD51, we have identified the
      human RAD51 (HsRAD51) subunit interface residues HsRad51(F129) in the Walker A
      box and HsRad51(H294) in the L2 ssDNA binding region as potentially important
      participants in salt-induced conformational transitions essential for recombinase
      activity. We demonstrate that the HsRad51(F129V) and HsRad51(H294V) substitution
      mutations reduce DNA dependent ATPase activity and are largely defective in the
      formation of a functional NPF, which ultimately eliminates recombinase catalytic
      functions. Our data are consistent with the conclusion that the HsRAD51(F129) and
      HsRAD51(H294) residues are important participants in the cation-induced
      allosteric activation of HsRAD51.

PMID- 21857995
TI  - Cloning of a novel protein interacting with BRS-3 and its effects in wound repair
      of bronchial epithelial cells.
AB  - Bombesin receptor subtype 3 (BRS-3), the orphan bombesin receptor, may play a
      role in the regulation of stress responses in lung and airway epithelia. Bombesin
      receptor activated protein (BRAP )is a novel protein we found in our previous
      study which interacts with BRS-3. This study was designed to observe the
      subcellular location and wound repair function of BRAP in human bronchial
      epithelial cells (HBECs). BRAP ORF was amplified by RT-PCR and ligated to pEGFP
      C1 vector, and then the recombinant plasmid pEGFP-C1-BRAP was transfected into
      Hela cells. The location of BRAP protein was observed by laser confocal
      microscope, and the expression of it was analyzed by Western-blot. At the same
      time,we built the recombinant plasmid pcDNA3.1(+)-BRAP, transfected it into HBECs
      and observed its impact on cell cycle and wound repair of HBECs. The results
      showed that BRAP locates in membrane and cytoplasm and increases significantly in
      transfected cells. Flow cytometry results demonstrated that the recombinant
      plasmid increases S phase plus G2 phase of cell cycle by 25%. Microscopic video
      analysis system showed that the repair index of wounded HBECs increases by 20%
      through stable expression of BRAP. The present study demonstrated that BRAP
      locates in the membrane and cytoplasm, suggesting that this protein is a
      cytoplasm protein, which promotes cell cycle and wound repair of HBECs.

PMID- 21857996
TI  - Efficient removal of platelets from peripheral blood progenitor cell products
      using a novel micro-chip based acoustophoretic platform.
AB  - BACKGROUND: Excessive collection of platelets is an unwanted side effect in
      current centrifugation-based peripheral blood progenitor cell (PBPC) apheresis.
      We investigated a novel microchip-based acoustophoresis technique, utilizing
      ultrasonic standing wave forces for the removal of platelets from PBPC products.
      By applying an acoustic standing wave field onto a continuously flowing cell
      suspension in a micro channel, cells can be separated from the surrounding media
      depending on their physical properties. STUDY DESIGN AND METHODS: PBPC samples
      were obtained from patients (n = 15) and healthy donors (n = 6) and sorted on an
      acoustophoresis-chip. The acoustic force was set to separate leukocytes from
      platelets into a target fraction and a waste fraction, respectively. The PBPC
      samples, the target and the waste fractions were analysed for cell recovery,
      purity and functionality. RESULTS: The median separation efficiency of leukocytes
      to the target fraction was 98% whereas platelets were effectively depleted by
      89%. PBPC samples and corresponding target fractions were similar in the
      percentage of CD34+ hematopoetic progenitor/stem cells as well as
      leukocyte/lymphocyte subset distributions. Median viability was 98%, 98% and 97%
      in the PBPC samples, the target and the waste fractions, respectively. Results
      from hematopoietic progenitor cell assays indicated a preserved colony-forming
      ability post-sorting. Evaluation of platelet activation by P-selectin (CD62P)
      expression revealed a significant increase of CD62P+ platelets in the target
      (19%) and waste fractions (20%), respectively, compared to the PBPC input samples
      (9%). However, activation was lower when compared to stored blood bank platelet
      concentrates (48%). CONCLUSION: Acoustophoresis can be utilized to efficiently
      deplete PBPC samples of platelets, whilst preserving the target stem/progenitor
      cell and leukocyte cell populations, cell viability and progenitor cell colony
      forming ability. Acoustophoresis is, thus, an interesting technology to improve
      current cell processing methods.

PMID- 21857997
TI  - Molecular interaction of TPPP with PrP antagonized the CytoPrP-induced disruption
      of microtubule structures and cytotoxicity.
AB  - BACKGROUND: Tubulin polymerization promoting protein/p25 (TPPP/p25), known as a
      microtubule-associated protein (MAP), is a brain-specific unstructured protein
      with a physiological function of stabilizing cellular microtubular
      ultrastructures. Whether TPPP involves in the normal functions of PrP or the
      pathogenesis of prion disease remains unknown. Here, we proposed the data that
      TPPP formed molecular complex with PrP. We also investigated its influence on the
      aggregation of PrP and fibrillization of PrP106-126 in vitro, its antagonization
      against the disruption of microtubule structures and cytotoxicity of cytosolic
      PrP in cells, and its alternation in the brains of scrapie-infected experimental
      hamsters. METHODOLOGY/PRINCIPAL FINDINGS: Using pull-down and immunoprecipitation
      assays, distinct molecular interaction between TPPP and PrP were identified and
      the segment of TPPP spanning residues 100-219 and the segment of PrP spanning
      residues 106-126 were mapped as the regions responsible for protein interaction.
      Sedimentation experiments found that TPPP increased the aggregation of full
      length recombinant PrP (PrP23-231) in vitro. Transmission electron microscopy and
      Thioflavin T (ThT) assays showed that TPPP enhanced fibril formation of synthetic
      peptide PrP106-126 in vitro. Expression of TPPP in the cultured cells did not
      obviously change the microtubule networks observed by a tubulin-specific
      immunofluorescent assay and cell growth features measured by CCK8 tests, but
      significantly antagonized the disruption of microtubule structures and rescued
      the cytotoxicity caused by the accumulation of cytosolic PrP (CytoPrP).
      Furthermore, Western blots identified that the levels of the endogenous TPPP in
      the brains of scrapie-infected experimental hamsters were significantly reduced.
      CONCLUSION/SIGNIFICANCE: Those data highlight TPPP may work as a protective
      factor for cells against the damage effects of the accumulation of abnormal forms
      of PrPs, besides its function as an agent for dynamic stabilization of
      microtubular ultrastructures.

PMID- 21857998
TI  - Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced
      by subacute and chronic inflammation.
AB  - Inflammation is known to be responsible for the sensitization of peripheral
      sensory neurons, leading to spontaneous pain and invalidating pain
      hypersensitivity. Given its role in regulating neuronal excitability, the voltage
      gated Nav1.9 channel is a potential target for the treatment of pathological
      pain, but its implication in inflammatory pain is yet not fully described. In the
      present study, we examined the role of the Nav1.9 channel in acute, subacute and
      chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. In
      mice we found that, although the Nav1.9 channel does not contribute to basal pain
      thresholds, it plays an important role in heat pain hypersensitivity induced by
      subacute paw inflammation (intraplantar carrageenan) and chronic ankle
      inflammation (complete Freund's adjuvant-induced monoarthritis). We showed for
      the first time that Nav1.9 also contributes to mechanical hypersensitivity in
      both models, as assessed using von Frey and dynamic weight bearing tests.
      Consistently, antisense-based Nav1.9 gene silencing in rats reduced carrageenan
      induced heat and mechanical pain hypersensitivity. While no changes in Nav1.9
      mRNA levels were detected in dorsal root ganglia (DRGs) during subacute and
      chronic inflammation, a significant increase in Nav1.9 immunoreactivity was
      observed in ipsilateral DRGs 24 hours following carrageenan injection. This was
      correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding
      the inflamed area. No change in Nav1.9 current density could be detected in the
      soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that
      newly produced channels may be non-functional at this level and rather contribute
      to the observed increase in axonal transport. Our results provide evidence that
      Nav1.9 plays a crucial role in the generation of heat and mechanical pain
      hypersensitivity, both in subacute and chronic inflammatory pain models, and
      bring new elements for the understanding of its regulation in those models.

PMID- 21858000
TI  - Chasing Jenner's vaccine: revisiting cowpox virus classification.
AB  - Cowpox virus (CPXV) is described as the source of the first vaccine used to
      prevent the onset and spread of an infectious disease. It is one of the earliest
      described members of the genus Orthopoxvirus, which includes the viruses that
      cause smallpox and monkeypox in humans. Both the historic and current literature
      describe "cowpox" as a disease with a single etiologic agent. Genotypic data
      presented herein indicate that CPXV is not a single species, but a composite of
      several (up to 5) species that can infect cows, humans, and other animals. The
      practice of naming agents after the host in which the resultant disease manifests
      obfuscates the true taxonomic relationships of "cowpox" isolates. These data
      support the elevation of as many as four new species within the traditional
      "cowpox" group and suggest that both wild and modern vaccine strains of Vaccinia
      virus are most closely related to CPXV of continental Europe rather than the
      United Kingdom, the homeland of the vaccine.

PMID- 21858001
TI  - Treatment interruption and variation in tablet taking behaviour result in viral
      failure: a case-control study from Cape Town, South Africa.
AB  - BACKGROUND: Understanding of the impact of non-structured treatment interruption
      (TI) and variation in tablet-taking on failure of first-line antiretroviral
      therapy (ART) is limited in a resource-poor setting. METHODS: A retrospective
      matched case-control analysis. Individuals failing ART were matched by time on
      ART with 4 controls. Viral load (VL) and CD4 count were completed 4-monthly.
      Adherence percentages, from tablet returns, were calculated 4-monthly (interval)
      and from ART start (cumulative). Variation between intervals and TI (>27 days off
      ART) were recorded. Conditional multivariate logistic regression analysis was
      performed to estimate the effect of cumulative adherence <90%, at least one
      episode of adherence variation >10% and TI on virological failure. Age, gender,
      baseline log VL and CD4 were included as possible confounders in the multivariate
      model. RESULTS: 244 patients (44 cases, 200 controls) were included. Median age
      was 32 years (IQR28-37), baseline CD4 108 cells/mm3 (IQR56-151), VL 4.82 log
      (IQR4.48-5.23). 94% (96% controls, 86% failures) had cumulative adherence >90%.
      The odds of failure increased 3 times (aOR 3.01, 95%CI 0.81-11.21) in individuals
      with cumulative adherence <90%, 2.2 times (aOR 2.20, 95%CI 1.04-4.64) in
      individuals with at least one episode of fluctuating adherence of >10% and 4.01
      times (aOR 4.01, 95%CI 1.45-11.10) in individuals with TIs. For individuals with
      TI and cumulative adherence >95%, the odds of failing were 5.65 (CI 1.40-22.85).
      CONCLUSION: It is well known that poor cumulative adherence increases risk of
      virological failure, but less well understood that TI and variations in tablet
      taking also play a key role, despite otherwise excellent adherence.

PMID- 21857999
TI  - Effectiveness of non-adjuvanted pandemic influenza A vaccines for preventing
      pandemic influenza acute respiratory illness visits in 4 U.S. communities.
AB  - We estimated the effectiveness of four monovalent pandemic influenza A (H1N1)
      vaccines (three unadjuvanted inactivated, one live attenuated) available in the
      U.S. during the pandemic. Patients with acute respiratory illness presenting to
      inpatient and outpatient facilities affiliated with four collaborating
      institutions were prospectively recruited, consented, and tested for influenza.
      Analyses were restricted to October 2009 through April 2010, when pandemic
      vaccine was available. Patients testing positive for pandemic influenza by real
      time RT-PCR were cases; those testing negative were controls. Vaccine
      effectiveness was estimated in logistic regression models adjusted for study
      community, patient age, timing of illness, insurance status, enrollment site, and
      presence of high-risk medical conditions. Pandemic virus was detected in 1,011
      (15%) of 6,757 enrolled patients. Fifteen (1%) of 1,011 influenza positive cases
      and 1,042 (18%) of 5,746 test-negative controls had record-verified pandemic
      vaccination >14 days prior to illness onset. Adjusted effectiveness (95%
      confidence interval) for pandemic vaccines combined was 56% (23%, 75%). Adjusted
      effectiveness for inactivated vaccines alone (79% of total) was 62% (25%, 81%)
      overall and 32% (-92%, 76%), 89% (15%, 99%), and -6% (-231%, 66%) in those aged
      0.5 to 9, 10 to 49, and 50+ years, respectively. Effectiveness for the live
      attenuated vaccine in those aged 2 to 49 years was only demonstrated if
      vaccination >7 rather than >14 days prior to illness onset was considered (61%?
      12%, 82%). Inactivated non-adjuvanted pandemic vaccines offered significant
      protection against confirmed pandemic influenza-associated medical care visits in
      young adults.

PMID- 21858002
TI  - Increased muscle stress-sensitivity induced by selenoprotein N inactivation in
      mouse: a mammalian model for SEPN1-related myopathy.
AB  - Selenium is an essential trace element and selenoprotein N (SelN) was the first
      selenium-containing protein shown to be directly involved in human inherited
      diseases. Mutations in the SEPN1 gene, encoding SelN, cause a group of muscular
      disorders characterized by predominant affection of axial muscles. SelN has been
      shown to participate in calcium and redox homeostasis, but its pathophysiological
      role in skeletal muscle remains largely unknown. To address SelN function in
      vivo, we generated a Sepn1-null mouse model by gene targeting. The Sepn1(-/-)
      mice had normal growth and lifespan, and were macroscopically indistinguishable
      from wild-type littermates. Only minor defects were observed in muscle morphology
      and contractile properties in SelN-deficient mice in basal conditions. However,
      when subjected to challenging physical exercise and stress conditions (forced
      swimming test), Sepn1(-/-) mice developed an obvious phenotype, characterized by
      limited motility and body rigidity during the swimming session, as well as a
      progressive curvature of the spine and predominant alteration of paravertebral
      muscles. This induced phenotype recapitulates the distribution of muscle
      involvement in patients with SEPN1-Related Myopathy, hence positioning this new
      animal model as a valuable tool to dissect the role of SelN in muscle function
      and to characterize the pathophysiological process.

PMID- 21858003
TI  - Functional analysis of the Phycomyces carRA gene encoding the enzymes phytoene
      synthase and lycopene cyclase.
AB  - Phycomyces carRA gene encodes a protein with two domains. Domain R is
      characterized by red carR mutants that accumulate lycopene. Domain A is
      characterized by white carA mutants that do not accumulate significant amounts of
      carotenoids. The carRA-encoded protein was identified as the lycopene cyclase and
      phytoene synthase enzyme by sequence homology with other proteins. However, no
      direct data showing the function of this protein have been reported so far.
      Different Mucor circinelloides mutants altered at the phytoene synthase, the
      lycopene cyclase or both activities were transformed with the Phycomyces carRA
      gene. Fully transcribed carRA mRNA molecules were detected by Northern assays in
      the transformants and the correct processing of the carRA messenger was verified
      by RT-PCR. These results showed that Phycomyces carRA gene was correctly
      expressed in Mucor. Carotenoids analysis in these transformants showed the
      presence of beta-carotene, absent in the untransformed strains, providing
      functional evidence that the Phycomyces carRA gene complements the M.
      circinelloides mutations. Co-transformation of the carRA cDNA in E. coli with
      different combinations of the carotenoid structural genes from Erwinia uredovora
      was also performed. Newly formed carotenoids were accumulated showing that the
      Phycomyces CarRA protein does contain lycopene cyclase and phytoene synthase
      activities. The heterologous expression of the carRA gene and the functional
      complementation of the mentioned activities are not very efficient in E. coli.
      However, the simultaneous presence of both carRA and carB gene products from
      Phycomyces increases the efficiency of these enzymes, presumably due to an
      interaction mechanism.

PMID- 21858004
TI  - Strategies for enhancing the accumulation and retention of extracellular matrix
      in tissue-engineered cartilage cultured in bioreactors.
AB  - Production of tissue-engineered cartilage involves the synthesis and accumulation
      of key constituents such as glycosaminoglycan (GAG) and collagen type II to form
      insoluble extracellular matrix (ECM). During cartilage culture, macromolecular
      components are released from nascent tissues into the medium, representing a
      significant waste of biosynthetic resources. This work was aimed at developing
      strategies for improving ECM retention in cartilage constructs and thus the
      quality of engineered tissues produced in bioreactors. Human chondrocytes seeded
      into polyglycolic acid (PGA) scaffolds were cultured in perfusion bioreactors for
      up to 5 weeks. Analysis of the size and integrity of proteoglycans in the
      constructs and medium showed that full-sized aggrecan was being stripped from the
      tissues without proteolytic degradation. Application of low (0.075 mL min(-1))
      and gradually increasing (0.075-0.2 mL min(-1)) medium flow rates in the
      bioreactor resulted in the generation of larger constructs, a 4.0-4.4-fold
      increase in the percentage of GAG retained in the ECM, and a 4.8-5.2-fold
      increase in GAG concentration in the tissues compared with operation at 0.2 mL
      min(-1). GAG retention was also improved by pre-culturing seeded scaffolds in
      flasks for 5 days prior to bioreactor culture. In contrast, GAG retention in PGA
      scaffolds infused with alginate hydrogel did not vary significantly with medium
      flow rate or pre-culture treatment. This work demonstrates that substantial
      improvements in cartilage quality can be achieved using scaffold and bioreactor
      culture strategies that specifically target and improve ECM retention.

PMID- 21858005
TI  - Coexpression of spectrally distinct rhodopsins in Aedes aegypti R7
      photoreceptors.
AB  - The retina of the mosquito Aedes aegypti can be divided into four regions based
      on the non-overlapping expression of a UV sensitive Aaop8 rhodopsin and a long
      wavelength sensitive Aaop2 type rhodopsin in the R7 photoreceptors. We show here
      that another rhodopsin, Aaop9, is expressed in all R7 photoreceptors and a subset
      of R8 photoreceptors. In the dorsal region, Aaop9 is expressed in both the cell
      body and rhabdomere of R7 and R8 cells. In other retinal regions Aaop9 is
      expressed only in R7 cells, being localized to the R7 rhabdomere in the central
      and ventral regions and in both the cell body and rhabdomere within the ventral
      stripe. Within the dorsal-central transition area ommatidia do not show a strict
      pairing of R7-R8 cell types. Thus, Aaop9 is coexpressed in the two classes of R7
      photoreceptors previously distinguished by the non-overlapping expression of
      Aaop8 and Aaop2 rhodopsins. Electroretinogram analysis of transgenic Drosophila
      shows that Aaop9 is a short wavelength rhodopsin with an optimal response to 400
      450 nm light. The coexpressed Aaop2 rhodopsin has dual wavelength sensitivity of
      500-550 nm and near 350 nm in the UV region. As predicted by the spectral
      properties of each rhodopsin, Drosophila photoreceptors expressing both Aaop9 and
      Aaop2 rhodopsins exhibit a uniform sensitivity across the broad 350-550 nm light
      range. We propose that rhodopsin coexpression is an adaptation within the R7
      cells to improve visual function in the low-light environments in which Ae.
      aegypti is active.

PMID- 21858006
TI  - Evolutionary genomics implies a specific function of Ant4 in mammalian and anole
      lizard male germ cells.
AB  - Most vertebrates have three paralogous genes with identical intron-exon
      structures and a high degree of sequence identity that encode mitochondrial
      adenine nucleotide translocase (Ant) proteins, Ant1 (Slc25a4), Ant2 (Slc25a5) and
      Ant3 (Slc25a6). Recently, we and others identified a fourth mammalian Ant
      paralog, Ant4 (Slc25a31), with a distinct intron-exon structure and a lower
      degree of sequence identity. Ant4 was expressed selectively in testis and sperm
      in adult mammals and was indeed essential for mouse spermatogenesis, but it was
      absent in birds, fish and frogs. Since Ant2 is X-linked in mammalian genomes, we
      hypothesized that the autosomal Ant4 gene may compensate for the loss of Ant2
      gene expression during male meiosis in mammals. Here we report that the Ant4
      ortholog is conserved in green anole lizard (Anolis carolinensis) and demonstrate
      that it is expressed in the anole testis. Further, a degenerate DNA fragment of
      putative Ant4 gene was identified in syntenic regions of avian genomes,
      indicating that Ant4 was present in the common amniote ancestor. Phylogenetic
      analyses suggest an even more ancient origin of the Ant4 gene. Although anole
      lizards are presumed male (XY) heterogametic, like mammals, copy numbers of the
      Ant2 as well as its neighboring gene were similar between male and female anole
      genomes, indicating that the anole Ant2 gene is either autosomal or located in
      the pseudoautosomal region of the sex chromosomes, in contrast to the case to
      mammals. These results imply the conservation of Ant4 is not likely simply driven
      by the sex chromosomal localization of the Ant2 gene and its subsequent
      inactivation during male meiosis. Taken together with the fact that Ant4 protein
      has a uniquely conserved structure when compared to other somatic Ant1, 2 and 3,
      there may be a specific advantage for mammals and lizards to express Ant4 in
      their male germ cells.

PMID- 21858007
TI  - Saccades and vergence performance in a population of children with vertigo and
      clinically assessed abnormal vergence capabilities.
AB  - PURPOSE: Early studies reported some abnormalities in saccade and vergence eye
      movements in children with vertigo and vergence deficiencies. The purpose of this
      study was to further examine saccade and vergence performance in a population of
      44 children (mean age: 12.3+/-1.6 years) with vertigo symptoms and with different
      levels of vergence abnormalities, as assessed by static orthoptic examination
      (near point of convergence, prism bar and cover-uncover test). METHODS: Three
      groups were identified on the basis of the orthoptic tests: group 1 (n = 13) with
      vergence spasms and mildly perturbed orthoptic scores, group 2 (n = 14) with
      moderately perturbed orthoptic scores, and group 3 (n = 17) with severely
      perturbed orthoptic scores. Data were compared to those recorded from 28 healthy
      children of similar ages. Latency, accuracy and peak velocity of saccades and
      vergence movements were measured in two different conditions: gap (fixation
      offset 200 ms prior to target onset) and simultaneous paradigms. Binocular
      horizontal movements were recorded by a photoelectric device. RESULTS: Group 2 of
      children with vergence abnormalities showed significantly longer latency than
      normal children in several types of eye movements recorded. For all three groups
      of children with vergence abnormalities, the gain was poor, particularly for
      vergence movement. The peak velocity values did not differ between the different
      groups of children examined. INTERPRETATION: Eye movement measures together with
      static orthoptic evaluation allowed us to better identify children with vergence
      abnormalities based on their slow initiation of eye movements. Overall, these
      findings support the hypothesis of a central deficit in the programming and
      triggering of saccades and vergence in these children.

PMID- 21858008
TI  - Performance of swabs, lavage, and diluents to quantify biomarkers of female
      genital tract soluble mucosal mediators.
AB  - BACKGROUND: Measurement of immune mediators and antimicrobial activity in female
      genital tract secretions may provide biomarkers predictive of risk for HIV-1
      acquisition and surrogate markers of microbicide safety. However, optimal methods
      for sample collection do not exist. This study compared collection methods.
      METHODS: Secretions were collected from 48 women (24 with bacterial vaginosis
      [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal
      lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or
      water (n = 14). The concentration of gluconate in Normosol-R CVL was determined
      to estimate the dilution factor. Cytokine and antimicrobial mediators were
      measured by Luminex or ELISA and corrected for protein content. Endogenous anti
      HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth.
      RESULTS: Higher concentrations of protein were recovered by CVL, despite a 10
      fold dilution of secretions, as compared to swab eluents. After protein
      correction, endocervical swabs recovered the highest mediator levels regardless
      of BV status. Endocervical and vaginal flocked swabs recovered significantly
      higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs
      (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R
      tended to recover higher levels of most mediators among women with BV, whereas
      saline or water tended to recover higher levels among women without BV. Saline
      recovered the highest levels of anti-HIV-1 activity regardless of BV status.
      CONCLUSIONS: Endocervical swabs and CVL collected with saline provide the best
      recovery of most mediators and would be the optimal sampling method(s) for
      clinical trials.

PMID- 21858009
TI  - Contrasting expression of canonical Wnt signaling reporters TOPGAL, BATGAL and
      Axin2(LacZ) during murine lung development and repair.
AB  - Canonical WNT signaling plays multiple roles in lung organogenesis and repair by
      regulating early progenitor cell fates: investigation has been enhanced by
      canonical Wnt reporter mice, TOPGAL, BATGAL and Axin2(LacZ). Although widely
      used, it remains unclear whether these reporters convey the same information
      about canonical Wnt signaling. We therefore compared beta-galactosidase
      expression patterns in canonical Wnt signaling of these reporter mice in whole
      embryo versus isolated prenatal lungs. To determine if expression varied further
      during repair, we analyzed comparative pulmonary expression of beta-galactosidase
      after naphthalene injury. Our data show important differences between reporter
      mice. While TOPGAL and BATGAL lines demonstrate Wnt signaling well in early lung
      epithelium, BATGAL expression is markedly reduced in late embryonic and adult
      lungs. By contrast, Axin2(LacZ) expression is sustained in embryonic lung
      mesenchyme as well as epithelium. Three days into repair after naphthalene,
      BATGAL expression is induced in bronchial epithelium as well as TOPGAL expression
      (already strongly expressed without injury). Axin2(LacZ) expression is increased
      in bronchial epithelium of injured lungs. Interestingly, both TOPGAL and
      Axin2(LacZ) are up regulated in parabronchial smooth muscle cells during repair.
      Therefore the optimal choice of Wnt reporter line depends on whether up- or down
      regulation of canonical Wnt signal reporting in either lung epithelium or
      mesenchyme is being compared.

PMID- 21858010
TI  - Mytilus galloprovincialis myticin C: a chemotactic molecule with antiviral
      activity and immunoregulatory properties.
AB  - Previous research has shown that an antimicrobial peptide (AMP) of the myticin
      class C (Myt C) is the most abundantly expressed gene in cDNA and suppressive
      subtractive hybridization (SSH) libraries after immune stimulation of mussel
      Mytilus galloprovincialis. However, to date, the expression pattern, the
      antimicrobial activities and the immunomodulatory properties of the Myt C peptide
      have not been determined. In contrast, it is known that Myt C mRNA presents an
      unusual and high level of polymorphism of unidentified biological significance.
      Therefore, to provide a better understanding of the features of this interesting
      molecule, we have investigated its function using four different cloned and
      expressed variants of Myt C cDNA and polyclonal anti-Myt C sera. The in vivo
      results suggest that this AMP, mainly present in hemocytes, could be acting as an
      immune system modulator molecule because its overexpression was able to alter the
      expression of mussel immune-related genes (as the antimicrobial peptides Myticin
      B and Mytilin B, the C1q domain-containing protein MgC1q, and lysozyme).
      Moreover, the in vitro results indicate that Myt C peptides have antimicrobial
      and chemotactic properties. Their recombinant expression in a fish cell line
      conferred protection against two different fish viruses (enveloped and non
      enveloped). Cell extracts from Myt C expressing fish cells were also able to
      attract hemocytes. All together, these results suggest that Myt C should be
      considered not only as an AMP but also as the first chemokine/cytokine-like
      molecule identified in bivalves and one of the few examples in all of the
      invertebrates.

PMID- 21858011
TI  - Evaluation of candidate genes from orphan FEB and GEFS+ loci by analysis of human
      brain gene expression atlases.
AB  - Febrile seizures, or febrile convulsions (FEB), represent the most common form of
      childhood seizures and are believed to be influenced by variations in several
      susceptibility genes. Most of the associated loci, however, remain 'orphan', i.e.
      the susceptibility genes they contain still remain to be identified. Further
      orphan loci have been mapped for a related disorder, genetic (generalized)
      epilepsy with febrile seizures plus (GEFS+).We show that both spatially mapped
      and 'traditional' gene expression data from the human brain can be successfully
      employed to predict the most promising candidate genes for FEB and GEFS+, apply
      our prediction method to the remaining orphan loci and discuss the validity of
      the predictions. For several of the orphan FEB/GEFS+ loci we propose excellent,
      and not always obvious, candidates for mutation screening in order to aid in
      gaining a better understanding of the genetic origin of the susceptibility to
      seizures.

PMID- 21858012
TI  - Human RAD18 interacts with ubiquitylated chromatin components and facilitates
      RAD9 recruitment to DNA double strand breaks.
AB  - RAD18 is an ubiquitin ligase involved in replicative damage bypass and DNA double
      strand break (DSB) repair processes. We found that RPA is required for the
      dynamic pattern of RAD18 localization during the cell cycle, and for accumulation
      of RAD18 at sites of gamma-irradiation-induced DNA damage. In addition, RAD18
      colocalizes with chromatin-associated conjugated ubiquitin and ubiquitylated H2A
      throughout the cell cycle and following irradiation. This localization pattern
      depends on the presence of an intact, ubiquitin-binding Zinc finger domain. Using
      a biochemical approach, we show that RAD18 directly binds to ubiquitylated H2A
      and several other unknown ubiquitylated chromatin components. This interaction
      also depends on the RAD18 Zinc finger, and increases upon the induction of DSBs
      by gamma-irradiation. Intriguingly, RAD18 does not always colocalize with regions
      that show enhanced H2A ubiquitylation. In human female primary fibroblasts, where
      one of the two X chromosomes is inactivated to equalize X-chromosomal gene
      expression between male (XY) and female (XX) cells, this inactive X is enriched
      for ubiquitylated H2A, but only rarely accumulates RAD18. This indicates that the
      binding of RAD18 to ubiquitylated H2A is context-dependent. Regarding the
      functional relevance of RAD18 localization at DSBs, we found that RAD18 is
      required for recruitment of RAD9, one of the components of the 9-1-1 checkpoint
      complex, to these sites. Recruitment of RAD9 requires the functions of the RING
      and Zinc finger domains of RAD18. Together, our data indicate that association of
      RAD18 with DSBs through ubiquitylated H2A and other ubiquitylated chromatin
      components allows recruitment of RAD9, which may function directly in DSB repair,
      independent of downstream activation of the checkpoint kinases CHK1 and CHK2.

PMID- 21858013
TI  - Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia
      (PCP).
AB  - BACKGROUND: Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging,
      particularly in developing countries. Highly sensitive diagnostic methods are
      costly, while less expensive methods often lack sensitivity or specificity. Cost
      effectiveness comparisons of the various diagnostic options have not been
      presented. METHODS AND FINDINGS: We compared cost-effectiveness, as measured by
      cost per life-years gained and proportion of patients successfully diagnosed and
      treated, of 33 PCP diagnostic options, involving combinations of specimen
      collection methods [oral washes, induced and expectorated sputum, and
      bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various
      staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis
      with chest x-ray alone. Our analyses were conducted from the perspective of the
      government payer among ambulatory, HIV-infected patients with symptoms of
      pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data
      were obtained from the National Institutes of Communicable Diseases in South
      Africa. At 50% disease prevalence, diagnostic procedures involving expectorated
      sputum with any PCR method, or induced sputum with nested or real-time PCR, were
      all highly cost-effective, successfully treating 77-90% of patients at $26-51 per
      life-year gained. Procedures using BAL specimens were significantly more
      expensive without added benefit, successfully treating 68-90% of patients at
      costs of $189-232 per life-year gained. A relatively cost-effective diagnostic
      procedure that did not require PCR was Toluidine Blue O staining of induced
      sputum ($25 per life-year gained, successfully treating 68% of patients).
      Diagnosis using chest x-rays alone resulted in successful treatment of 77% of
      patients, though cost-effectiveness was reduced ($109 per life-year gained)
      compared with several molecular diagnostic options. CONCLUSIONS: For diagnosis of
      PCP, use of PCR technologies, when combined with less-invasive patient specimens
      such as expectorated or induced sputum, represent more cost-effective options
      than any diagnostic procedure using BAL, or chest x-ray alone.

PMID- 21858014
TI  - Comprehensive structural and substrate specificity classification of the
      Saccharomyces cerevisiae methyltransferome.
AB  - Methylation is one of the most common chemical modifications of biologically
      active molecules and it occurs in all life forms. Its functional role is very
      diverse and involves many essential cellular processes, such as signal
      transduction, transcriptional control, biosynthesis, and metabolism. Here, we
      provide further insight into the enzymatic methylation in S. cerevisiae by
      conducting a comprehensive structural and functional survey of all the
      methyltransferases encoded in its genome. Using distant homology detection and
      fold recognition, we found that the S. cerevisiae methyltransferome comprises 86
      MTases (53 well-known and 33 putative with unknown substrate specificity).
      Structural classification of their catalytic domains shows that these enzymes may
      adopt nine different folds, the most common being the Rossmann-like. We also
      analyzed the domain architecture of these proteins and identified several new
      domain contexts. Interestingly, we found that the majority of MTase genes are
      periodically expressed during yeast metabolic cycle. This finding, together with
      calculated isoelectric point, fold assignment and cellular localization, was used
      to develop a novel approach for predicting substrate specificity. Using this
      approach, we predicted the general substrates for 24 of 33 putative MTases and
      confirmed these predictions experimentally in both cases tested. Finally, we show
      that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein
      MTases, eight small molecule MTases, three lipid MTases, and nine MTases with
      still unknown substrate specificity.

PMID- 21858015
TI  - All clinically-relevant blood components transmit prion disease following a
      single blood transfusion: a sheep model of vCJD.
AB  - Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from
      the consumption of BSE-contaminated meat products. Whilst the epidemic appears to
      be waning, there is much concern that vCJD infection may be perpetuated in humans
      by the transfusion of contaminated blood products. Since 2004, several cases of
      transfusion-associated vCJD transmission have been reported and linked to blood
      collected from pre-clinically affected donors. Using an animal model in which the
      disease manifested resembles that of humans affected with vCJD, we examined which
      blood components used in human medicine are likely to pose the greatest risk of
      transmitting vCJD via transfusion. We collected two full units of blood from BSE
      infected donor animals during the pre-clinical phase of infection. Using methods
      employed by transfusion services we prepared red cell concentrates, plasma and
      platelets units (including leucoreduced equivalents). Following transfusion, we
      showed that all components contain sufficient levels of infectivity to cause
      disease following only a single transfusion and also that leucoreduction did not
      prevent disease transmission. These data suggest that all blood components are
      vectors for prion disease transmission, and highlight the importance of multiple
      control measures to minimise the risk of human to human transmission of vCJD by
      blood transfusion.

PMID- 21858016
TI  - Hessian fly-associated bacteria: transmission, essentiality, and composition.
AB  - Plant-feeding insects have been recently found to use microbes to manipulate host
      plant physiology and morphology. Gall midges are one of the largest groups of
      insects that manipulate host plants extensively. Hessian fly (HF, Mayetiola
      destructor) is an important pest of wheat and a model system for studying gall
      midges. To examine the role of bacteria in parasitism, a systematic analysis of
      bacteria associated with HF was performed for the first time. Diverse bacteria
      were found in different developmental HF stages. Fluorescent in situ
      hybridization detected a bacteriocyte-like structure in developing eggs.
      Bacterial DNA was also detected in eggs by PCR using primers targeted to
      different bacterial groups. These results indicated that HF hosted different
      types of bacteria that were maternally transmitted to the next generation.
      Eliminating bacteria from the insect with antibiotics resulted in high mortality
      of HF larvae, indicating that symbiotic bacteria are essential for the insect to
      survive on wheat seedlings. A preliminary survey identified various types of
      bacteria associated with different HF stages, including the genera Enterobacter,
      Pantoea, Stenotrophomonas, Pseudomonas, Bacillus, Ochrobactrum, Acinetobacter,
      Alcaligenes, Nitrosomonas, Arcanobacterium, Microbacterium, Paenibacillus, and
      Klebsiella. Similar bacteria were also found specifically in HF-infested
      susceptible wheat, suggesting that HF larvae had either transmitted bacteria into
      plant tissue or brought secondary infection of bacteria to the wheat host. The
      bacteria associated with wheat seedlings may play an essential role in the wheat
      HF interaction.

PMID- 21858017
TI  - Behavioral and autonomic responses to acute restraint stress are segregated
      within the lateral septal area of rats.
AB  - BACKGROUND: The Lateral Septal Area (LSA) is involved with autonomic and behavior
      responses associated to stress. In rats, acute restraint (RS) is an unavoidable
      stress situation that causes autonomic (body temperature, mean arterial pressure
      (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like
      behavior) changes in rats. The LSA is one of several brain regions that have been
      involved in stress responses. The aim of the present study was to investigate if
      the neurotransmission blockade in the LSA would interfere in the autonomic and
      behavioral changes induced by RS. METHODOLOGY/PRINCIPAL FINDINGS: Male Wistar
      rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for
      recording internal body temperature), and an implanted catheter into the femoral
      artery (for recording and cardiovascular parameters) were used. They received
      bilateral microinjections of the non-selective synapse blocker cobalt chloride
      (CoCl(2), 1 mM/ 100 nL) or vehicle 10 min before RS session. The tail temperature
      was measured by an infrared thermal imager during the session. Twenty-four h
      after the RS session the rats were tested in the elevated plus maze (EPM).
      CONCLUSIONS/SIGNIFICANCE: Inhibition of LSA neurotransmission reduced the MAP and
      HR increases observed during RS. However, no changes were observed in the
      decrease in skin temperature and increase in internal body temperature observed
      during this period. Also, LSA inhibition did not change the anxiogenic effect
      induced by RS observed 24 h later in the EPM. The present results suggest that
      LSA neurotransmission is involved in the cardiovascular but not the temperature
      and behavioral changes induced by restraint stress.

PMID- 21858018
TI  - High-resolution measurements of face-to-face contact patterns in a primary
      school.
AB  - BACKGROUND: Little quantitative information is available on the mixing patterns
      of children in school environments. Describing and understanding contacts between
      children at school would help quantify the transmission opportunities of
      respiratory infections and identify situations within schools where the risk of
      transmission is higher. We report on measurements carried out in a French school
      (6-12 years children), where we collected data on the time-resolved face-to-face
      proximity of children and teachers using a proximity-sensing infrastructure based
      on radio frequency identification devices. METHODS AND FINDINGS: Data on face-to
      face interactions were collected on Thursday, October 1(st) and Friday, October
      2(nd) 2009. We recorded 77,602 contact events between 242 individuals (232
      children and 10 teachers). In this setting, each child has on average 323
      contacts per day with 47 other children, leading to an average daily interaction
      time of 176 minutes. Most contacts are brief, but long contacts are also
      observed. Contacts occur mostly within each class, and each child spends on
      average three times more time in contact with classmates than with children of
      other classes. We describe the temporal evolution of the contact network and the
      trajectories followed by the children in the school, which constrain the contact
      patterns. We determine an exposure matrix aimed at informing mathematical models.
      This matrix exhibits a class and age structure which is very different from the
      homogeneous mixing hypothesis. CONCLUSIONS: We report on important properties of
      the contact patterns between school children that are relevant for modeling the
      propagation of diseases and for evaluating control measures. We discuss public
      health implications related to the management of schools in case of epidemics and
      pandemics. Our results can help define a prioritization of control measures based
      on preventive measures, case isolation, classes and school closures, that could
      reduce the disruption to education during epidemics.

PMID- 21858019
TI  - Two alternating motor programs drive navigation in Drosophila larva.
AB  - When placed on a temperature gradient, a Drosophila larva navigates away from
      excessive cold or heat by regulating the size, frequency, and direction of
      reorientation maneuvers between successive periods of forward movement. Forward
      movement is driven by peristalsis waves that travel from tail to head. During
      each reorientation maneuver, the larva pauses and sweeps its head from side to
      side until it picks a new direction for forward movement. Here, we characterized
      the motor programs that underlie the initiation, execution, and completion of
      reorientation maneuvers by measuring body segment dynamics of freely moving
      larvae with fluorescent muscle fibers as they were exposed to temporal changes in
      temperature. We find that reorientation maneuvers are characterized by highly
      stereotyped spatiotemporal patterns of segment dynamics. Reorientation maneuvers
      are initiated with head sweeping movement driven by asymmetric contraction of a
      portion of anterior body segments. The larva attains a new direction for forward
      movement after head sweeping movement by using peristalsis waves that gradually
      push posterior body segments out of alignment with the tail (i.e., the previous
      direction of forward movement) into alignment with the head. Thus, reorientation
      maneuvers during thermotaxis are carried out by two alternating motor programs:
      (1) peristalsis for driving forward movement and (2) asymmetric contraction of
      anterior body segments for driving head sweeping movement.

PMID- 21858020
TI  - Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic
      characterization of rare microdeletions.
AB  - BACKGROUND: Patients with epilepsy often suffer from other important conditions.
      The existence of such co-morbidities is frequently not recognized and their
      relationship with epilepsy usually remains unexplained. METHODOLOGY/PRINCIPAL
      FINDINGS: We describe three patients with common, sporadic, non-syndromic
      epilepsies in whom large genomic microdeletions were found during a study of
      genetic susceptibility to epilepsy. We performed detailed gene-driven clinical
      investigations in each patient. Disruption of the function of genes in the
      deleted regions can explain co-morbidities in these patients.
      CONCLUSIONS/SIGNIFICANCE: Co-morbidities in patients with epilepsy can be part of
      a genomic abnormality even in the absence of (known) congenital malformations or
      intellectual disabilities. Gene-driven phenotype examination can also reveal
      clinically significant unsuspected condition.

PMID- 21858021
TI  - Elevated non-esterified fatty acid concentrations during bovine oocyte maturation
      compromise early embryo physiology.
AB  - Elevated concentrations of serum non-esterified fatty acids (NEFA), associated
      with maternal disorders such as obesity and type II diabetes, alter the ovarian
      follicular micro-environment and have been associated with subfertility arising
      from reduced oocyte developmental competence. We have asked whether elevated NEFA
      concentrations during oocyte maturation affect the development and physiology of
      zygotes formed from such oocytes, using the cow as a model. The zygotes were
      grown to blastocysts, which were evaluated for their quality in terms of cell
      number, apoptosis, expression of key genes, amino acid turnover and oxidative
      metabolism. Oocyte maturation under elevated NEFA concentrations resulted in
      blastocysts with significantly lower cell number, increased apoptotic cell ratio
      and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the
      blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up
      regulated lactate consumption and higher amino acid metabolism. These data
      indicate that exposure of maturing oocytes to elevated NEFA concentrations has a
      negative impact on fertility not only through a reduction in oocyte developmental
      capacity but through compromised early embryo quality, viability and metabolism.

PMID- 21858022
TI  - IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading
      to late fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable
      disease. We demonstrated recently the predominant role of the NLRP3 inflammasome
      activation and IL-1beta expression in the establishment of pulmonary inflammation
      and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary
      inflammation and fibrosis was assessed using the bleomycin model in deficient
      mice. RESULTS: We show that bleomycin or IL-1beta-induced lung injury leads to
      increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL
      23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for
      inflammatory response to BLM as shown with gene deficient mice or mice treated
      with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A
      and IL-17F expression by RORgammat(+) gammadelta T cells and to a lesser extent
      by CD4alphabeta(+) T cells, but not by iNKT cells, 24 hrs after BLM
      administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling
      are necessary to pulmonary TGF-beta1 production, collagen deposition and
      evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an
      early IL-1beta-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis
      and identify innate IL-23 and IL-17A as interesting drug targets for IL-1beta
      driven lung pathology.

PMID- 21858023
TI  - Targeting RNA by small molecules: comparative structural and thermodynamic
      aspects of aristololactam-beta-D-glucoside and daunomycin binding to tRNA(phe).
AB  - BACKGROUND: Interaction of aristololactam-beta-D-glucoside and daunomycin with
      tRNA(phe) was investigated using various biophysical techniques.
      METHODOLOGY/PRINCIPAL FINDINGS: Absorption and fluorescence studies revealed that
      both the compounds bind tRNA(phe) non-cooperatively. The binding of daunomycin
      was about one order of magnitude higher than that of aristololactam-beta-D
      glucoside. Stronger binding of the former was also inferred from fluorescence
      quenching data, quantum efficiency values and circular dichroic results. Results
      from isothermal titration calorimetry experiments suggested that the binding of
      both compounds was predominantly entropy driven with a smaller but favorable
      enthalpy term that increased with temperature. A large favorable electrostatic
      contribution to the binding of daunomycin to tRNA(phe) was revealed from salt
      dependence data and the dissection of the free energy values. The electrostatic
      component to the free energy change for aristololactam-beta-D-glucoside-tRNA(phe)
      interaction was smaller than that of daunomycin. This was also inferred from the
      slope of log K versus [Na(+)] plots. Both compounds enhanced the thermal
      stability of tRNA(phe). The small heat capacity changes of -47 and -99 cal/mol K,
      respectively, observed for aristololactam-beta-D-glucoside and daunomycin, and
      the observed enthalpy-entropy compensation phenomenon confirmed the involvement
      of multiple weak noncovalent interactions. Molecular aspects of the interaction
      have been revealed. CONCLUSIONS/SIGNIFICANCE: This study presents the structural
      and energetic aspects of the binding of aristololactam-beta-D-glucoside and
      daunomycin to tRNA(phe).

PMID- 21858024
TI  - Permeation through the cell membrane of a boron-based beta-lactamase inhibitor.
AB  - Bacteria express beta-lactamases to counteract the beneficial action of
      antibiotics. Benzo[b]-thiophene-2-boronic acid (BZB) derivatives are beta
      lactamase inhibitors and, as such, promising compounds to be associated with beta
      lactam antibacterial therapies. The uncharged form of BZB, in particular, is
      suggested to diffuse through the outer membrane of gram negative bacteria. In
      this study, through the combination of electrophysiological experiments across
      reconstituted PC/n-decane bilayers and metadynamics-based free energy
      calculations, we investigate the permeation mechanism of boronic compounds. Our
      experimental data establish that BZB passes through the membrane, while computer
      simulations provide hints for the existence of an aqueous, water-filled
      monomolecular channel. These findings provide new perspectives for the design of
      boronic acid derivatives with high membrane permeability.

PMID- 21858025
TI  - Cell cycle regulation and cytoskeletal remodelling are critical processes in the
      nutritional programming of embryonic development.
AB  - Many mechanisms purport to explain how nutritional signals during early
      development are manifested as disease in the adult offspring. While these
      describe processes leading from nutritional insult to development of the actual
      pathology, the initial underlying cause of the programming effect remains
      elusive. To establish the primary drivers of programming, this study aimed to
      capture embryonic gene and protein changes in the whole embryo at the time of
      nutritional insult rather than downstream phenotypic effects. By using a cross
      over design of two well established models of maternal protein and iron
      restriction we aimed to identify putative common "gatekeepers" which may drive
      nutritional programming.Both protein and iron deficiency in utero reduced the
      nephron complement in adult male Wistar and Rowett Hooded Lister rats (P<0.05).
      This occurred in the absence of damage to the glomerular ultrastructure.
      Microarray, proteomic and pathway analyses identified diet-specific and strain
      specific gatekeeper genes, proteins and processes which shared a common
      association with the regulation of the cell cycle, especially the G1/S and G2/M
      checkpoints, and cytoskeletal remodelling. A cell cycle-specific PCR array
      confirmed the down-regulation of cyclins with protein restriction and the up
      regulation of apoptotic genes with iron deficiency.The timing and experimental
      design of this study have been carefully controlled to isolate the common
      molecular mechanisms which may initiate the sequelae of events involved in
      nutritional programming of embryonic development. We propose that despite
      differences in the individual genes and proteins affected in each strain and with
      each diet, the general response to nutrient deficiency in utero is perturbation
      of the cell cycle, at the level of interaction with the cytoskeleton and the
      mitotic checkpoints, thereby diminishing control over the integrity of DNA which
      is allowed to replicate. These findings offer novel insight into the primary
      causes and mechanisms leading to the pathologies which have been identified by
      previous programming studies.

PMID- 21858026
TI  - Olfactory impairment is correlated with confabulation in alcoholism: towards a
      multimodal testing of orbitofrontal cortex.
AB  - BACKGROUND: Olfactory abilities are now a flourishing field in psychiatry
      research. As the orbitofrontal cortex appears to be simultaneously implicated in
      odour processing and executive impairments, it has been proposed that olfaction
      could constitute a cognitive marker of psychiatric states. While this assumption
      appears promising, very few studies have been conducted on this topic among
      psychopathological populations. The present study thus aimed at exploring the
      links between olfaction and executive functions. These links were evaluated using
      two tasks of comparable difficulty, one known to rely on orbitofrontal cortex
      processing (i.e., a confabulation task), and one not associated with this area
      (i.e., Stop-Signal task). METHODOLOGY/PRINCIPAL FINDINGS: Twenty recently
      detoxified alcoholic individuals and twenty paired controls took part in an
      experiment evaluating olfactory abilities and executive functioning (i.e., Stop
      Signal task and confabulation task). Comorbidities and potential biasing
      variables were also controlled for. Alcoholic individuals exhibited impaired
      performance for high-level olfactory processing and significant confabulation
      problems as compared to controls (but no deficit in Stop-Signal task), even when
      the influence of comorbidities was taken into account. Most importantly,
      olfactory abilities and confabulation rates were significantly correlated in both
      groups. CONCLUSIONS/SIGNIFICANCE: Alcoholism jointly leads to olfactory and
      memory source impairments, and these two categories of deficits are associated.
      These results strongly support the proposition that olfactory and confabulation
      measures both index orbitofrontal functioning, and suggest that olfaction could
      become a reliable cognitive marker in psychiatric disorders. Moreover, it
      underlines the need to take into account these olfactory and source memory
      impairments in a clinical context.

PMID- 21858027
TI  - A robust statistical method for association-based eQTL analysis.
AB  - BACKGROUND: It has been well established that theoretical kernel for recently
      surging genome-wide association study (GWAS) is statistical inference of linkage
      disequilibrium (LD) between a tested genetic marker and a putative locus
      affecting a disease trait. However, LD analysis is vulnerable to several
      confounding factors of which population stratification is the most prominent.
      Whilst many methods have been proposed to correct for the influence either
      through predicting the structure parameters or correcting inflation in the test
      statistic due to the stratification, these may not be feasible or may impose
      further statistical problems in practical implementation. METHODOLOGY: We propose
      here a novel statistical method to control spurious LD in GWAS from population
      structure by incorporating a control marker into testing for significance of
      genetic association of a polymorphic marker with phenotypic variation of a
      complex trait. The method avoids the need of structure prediction which may be
      infeasible or inadequate in practice and accounts properly for a varying effect
      of population stratification on different regions of the genome under study.
      Utility and statistical properties of the new method were tested through an
      intensive computer simulation study and an association-based genome-wide mapping
      of expression quantitative trait loci in genetically divergent human populations.
      RESULTS/CONCLUSIONS: The analyses show that the new method confers an improved
      statistical power for detecting genuine genetic association in subpopulations and
      an effective control of spurious associations stemmed from population structure
      when compared with other two popularly implemented methods in the literature of
      GWAS.

PMID- 21858028
TI  - Morphological diversity between culture strains of a chlorarachniophyte,
      Lotharella globosa.
AB  - Chlorarachniophytes are marine unicellular algae that possess secondary plastids
      of green algal origin. Although chlorarachniophytes are a small group (the phylum
      of Chlorarachniophyta contains 14 species in 8 genera), they have variable and
      complex life cycles that include amoeboid, coccoid, and/or flagellate cells. The
      majority of chlorarachniophytes possess two or more cell types in their life
      cycles, and which cell types are found is one of the principle morphological
      criteria used for species descriptions. Here we describe an unidentified
      chlorarachniophyte that was isolated from an artificial coral reef that calls
      this criterion into question. The life cycle of the new strain includes all three
      major cell types, but DNA barcoding based on the established nucleomorph ITS
      sequences showed it to share 100% sequence identity with Lotharella globosa. The
      type strain of L. globosa was also isolated from a coral reef, but is defined as
      completely lacking an amoeboid stage throughout its life cycle. We conclude that
      L. globosa possesses morphological diversity between culture strains, and that
      the new strain is a variety of L. globosa, which we describe as Lotharella
      globosa var. fortis var. nov. to include the amoeboid stage in the formal
      description of L. globosa. This intraspecies variation suggest that gross
      morphological stages maybe lost rather rapidly, and specifically that the type
      strain of L. globosa has lost the ability to form the amoeboid stage, perhaps
      recently. This in turn suggests that even major morphological characters used for
      taxonomy of this group may be variable in natural populations, and therefore
      misleading.

PMID- 21858029
TI  - Curcumin inhibits neuronal and vascular degeneration in retina after ischemia and
      reperfusion injury.
AB  - BACKGROUND: Neuron loss, glial activation and vascular degeneration are common
      sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present
      study was conducted to explore the ability of curcumin to inhibit retinal I/R
      injury, and to investigate underlying mechanisms of the drug effects.
      METHODOLOGY/PRINCIPAL FINDINGS: Different dosages of curcumin were administered.
      I/R injury was induced by elevating the intraocular pressure for 60 min followed
      by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic
      cells in the ganglion cell layer (GCL) were quantitated, and the number of
      degenerate capillaries was assessed. The activation of glial cells was measured
      by the expression level of GFAP. Signaling pathways including IKK-IkappaBalpha,
      JAK-STAT1/3, ERK/MAPK and the expression levels of beta-tubulin III and MCP-1
      were measured by western blot analysis. Pre-treatment using 0.01%-0.25% curcumin
      in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre
      treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL
      positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R
      induced up-regulation of MCP-1, IKKalpha, p-IkappaBalpha and p-STAT3 (Tyr), and
      down-regulation of beta-tubulin III. This dose showed no effect on injury-induced
      GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the
      injury also showed a vaso-protective effect. CONCLUSIONS/SIGNIFICANCE: Curcumin
      protects retinal neurons and microvessels against I/R injury. The beneficial
      effects of curcumin on neurovascular degeneration may occur through its
      inhibitory effects on injury-induced activation of NF-kappaB and STAT3, and on
      over-expression of MCP-1. Curcumin may therefore serve as a promising candidate
      for retinal ischemic diseases.

PMID- 21858030
TI  - Molecular characterization and phylogenetic study of coxsackievirus A24v causing
      outbreaks of acute hemorrhagic conjunctivitis (AHC) in Brazil.
AB  - BACKGROUND: Coxsackievirus A24 variant (CA24v) is the most prevalent viral
      pathogen associated with acute hemorrhagic conjunctivitis (AHC) outbreaks.
      Sixteen years after its first outbreak in Brazil, this agent reemerged in 2003 in
      Brazil, spread to nearly all states and caused outbreaks until 2005. In 2009, a
      new outbreak occurred in the northeast region of the country. In this study, we
      performed a viral isolation in cell culture and characterized clinical samples
      collected from patients presenting symptoms during the outbreak of 2005 in
      Vitoria, Espirito Santo State (ES) and the outbreak of 2009 in Recife, Pernambuco
      State (PE). We also performed a phylogenetic analysis of worldwide strains and
      all meaningful Brazilian isolates since 2003. METHODS AND FINDINGS: Sterile
      cotton swabs were used to collect eye discharges, and all 210 clinical samples
      were used to inoculate cell cultures. Cytopathic effects in HEp-2 cells were seen
      in 58 of 180 (32%) samples from Vitoria and 3 of 30 (10%) samples from Recife.
      Phylogenetic analysis based on a fragment of the VP1 and 3C gene revealed that
      the CA24v causing outbreaks in Brazil during the years 2003, 2004 and 2005
      evolved from Asian isolates that had caused the South Korean outbreak of AHC
      during the summer of 2002. However, the 2009 outbreak of AHC in Pernambuco was
      originated from the reintroduction of a new CA24v strain that was circulating
      during 2007 in Asia, where CA24v outbreaks has been continuously reported since
      1970. CONCLUSIONS: This study is the first phylogenetic analysis of AHC outbreaks
      caused by CA24v in Brazil. The results showed that Asian strains of CA24v were
      responsible for the outbreaks since 1987 and were independently introduced to
      Brazil in 2003 and 2009. Phylogenetic analysis of complete VP1 gene is a useful
      tool for studying the epidemiology of enteroviruses associated with outbreaks.

PMID- 21858031
TI  - LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent
      of LRRK2 GTP binding.
AB  - Leucine rich repeat kinase 2 (LRRK2) is a Parkinson's disease (PD) gene that
      encodes a large multidomain protein including both a GTPase and a kinase domain.
      GTPases often regulate kinases within signal transduction cascades, where GTPases
      act as molecular switches cycling between a GTP bound "on" state and a GDP bound
      "off" state. It has been proposed that LRRK2 kinase activity may be increased
      upon GTP binding at the LRRK2 Ras of complex proteins (ROC) GTPase domain. Here
      we extensively test this hypothesis by measuring LRRK2 phosphorylation activity
      under influence of GDP, GTP or non-hydrolyzable GTP analogues GTPgammaS or
      GMPPCP. We show that autophosphorylation and lrrktide phosphorylation activity of
      recombinant LRRK2 protein is unaltered by guanine nucleotides, when co-incubated
      with LRRK2 during phosphorylation reactions. Also phosphorylation activity of
      LRRK2 is unchanged when the LRRK2 guanine nucleotide binding pocket is previously
      saturated with various nucleotides, in contrast to the greatly reduced activity
      measured for the guanine nucleotide binding site mutant T1348N. Interestingly,
      when nucleotides were incubated with cell lysates prior to purification of LRRK2,
      kinase activity was slightly enhanced by GTPgammaS or GMPPCP compared to GDP,
      pointing to an upstream guanine nucleotide binding protein that may activate
      LRRK2 in a GTP-dependent manner. Using metabolic labeling, we also found that
      cellular phosphorylation of LRRK2 was not significantly modulated by nucleotides,
      although labeling is significantly reduced by guanine nucleotide binding site
      mutants. We conclude that while kinase activity of LRRK2 requires an intact ROC
      GTPase domain, it is independent of GDP or GTP binding to ROC.

PMID- 21858032
TI  - Successful in vitro expansion and differentiation of cord blood derived CD34+
      cells into early endothelial progenitor cells reveals highly differential gene
      expression.
AB  - Endothelial progenitor cells (EPCs) can be purified from peripheral blood, bone
      marrow or cord blood and are typically defined by a limited number of cell
      surface markers and a few functional tests. A detailed in vitro characterization
      is often restricted by the low cell numbers of circulating EPCs. Therefore in
      vitro culturing and expansion methods are applied, which allow at least
      distinguishing two different types of EPCs, early and late EPCs. Herein, we
      describe an in vitro culture technique with the aim to generate high numbers of
      phenotypically, functionally and genetically defined early EPCs from human cord
      blood. Characterization of EPCs was done by flow cytometry, immunofluorescence
      microscopy, colony forming unit (CFU) assay and endothelial tube formation assay.
      There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2,
      CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex
      lectin binding. The cells stimulated endothelial tube formation only in co
      cultures with mature endothelial cells and formed CFUs. Microarray analysis
      revealed highly up-regulated genes, including LL-37 (CAMP), PDK4, and alpha-2
      macroglobulin. In addition, genes known to be associated with cardioprotective
      (GDF15) or pro-angiogenic (galectin-3) properties were also significantly up
      regulated after a 72 h differentiation period on fibronectin. We present a novel
      method that allows to generate high numbers of phenotypically, functionally and
      genetically characterized early EPCs. Furthermore, we identified several genes
      newly linked to EPC differentiation, among them LL-37 (CAMP) was the most up
      regulated gene.

PMID- 21858033
TI  - Annotation of two large contiguous regions from the Haemonchus contortus genome
      using RNA-seq and comparative analysis with Caenorhabditis elegans.
AB  - The genomes of numerous parasitic nematodes are currently being sequenced, but
      their complexity and size, together with high levels of intra-specific sequence
      variation and a lack of reference genomes, makes their assembly and annotation a
      challenging task. Haemonchus contortus is an economically significant parasite of
      livestock that is widely used for basic research as well as for vaccine
      development and drug discovery. It is one of many medically and economically
      important parasites within the strongylid nematode group. This group of parasites
      has the closest phylogenetic relationship with the model organism Caenorhabditis
      elegans, making comparative analysis a potentially powerful tool for genome
      annotation and functional studies. To investigate this hypothesis, we sequenced
      two contiguous fragments from the H. contortus genome and undertook detailed
      annotation and comparative analysis with C. elegans. The adult H. contortus
      transcriptome was sequenced using an Illumina platform and RNA-seq was used to
      annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a
      181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative
      transposable elements were identified. 97.5% of the annotated genes had
      detectable homologues in C. elegans of which 60% had putative orthologues,
      significantly higher than previous analyses based on EST analysis. Gene density
      appears to be less in H. contortus than in C. elegans, with annotated H.
      contortus genes being an average of two-to-three times larger than their putative
      C. elegans orthologues due to a greater intron number and size. Synteny appears
      high but gene order is generally poorly conserved, although areas of conserved
      microsynteny are apparent. C. elegans operons appear to be partially conserved in
      H. contortus. Our findings suggest that a combination of RNA-seq and comparative
      analysis with C. elegans is a powerful approach for the annotation and analysis
      of strongylid nematode genomes.

PMID- 21858034
TI  - Common minor histocompatibility antigen discovery based upon patient clinical
      outcomes and genomic data.
AB  - BACKGROUND: Minor histocompatibility antigens (mHA) mediate much of the graft vs.
      leukemia (GvL) effect and graft vs. host disease (GvHD) in patients who undergo
      allogeneic stem cell transplantation (SCT). Therapeutic decision making and
      treatments based upon mHAs will require the evaluation of multiple candidate mHAs
      and the selection of those with the potential to have the greatest impact on
      clinical outcomes. We hypothesized that common, immunodominant mHAs, which are
      presented by HLA-A, B, and C molecules, can mediate clinically significant GvL
      and/or GvHD, and that these mHAs can be identified through association of genomic
      data with clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: Because most mHAs
      result from donor/recipient cSNP disparities, we genotyped 57 myeloid leukemia
      patients and their donors at 13,917 cSNPs. We correlated the frequency of
      genetically predicted mHA disparities with clinical evidence of an immune
      response and then computationally screened all peptides mapping to the highly
      associated cSNPs for their ability to bind to HLA molecules. As proof-of-concept,
      we analyzed one predicted antigen, T4A, whose mHA mismatch trended towards
      improved overall and disease free survival in our cohort. T4A mHA mismatches
      occurred at the maximum theoretical frequency for any given SCT. T4A-specific
      CD8+ T lymphocytes (CTLs) were detected in 3 of 4 evaluable post-transplant
      patients predicted to have a T4A mismatch. CONCLUSIONS/SIGNIFICANCE: Our method
      is the first to combine clinical outcomes data with genomics and bioinformatics
      methods to predict and confirm a mHA. Refinement of this method should enable the
      discovery of clinically relevant mHAs in the majority of transplant patients and
      possibly lead to novel immunotherapeutics.

PMID- 21858035
TI  - The role of serum biomarkers in predicting fibrosis progression in pediatric and
      adult hepatitis C virus chronic infection.
AB  - BACKGROUND/AIMS: Liver biopsy represents the gold standard for damage evaluation,
      but noninvasive serum markers that mirror liver fibrosis progression are actual
      goals both in adults and especially in children. The aim was to determine
      specific serum markers that correlate with liver fibrosis progression during
      chronic HCV infection. METHODS: Liver biopsies and concomitant serum samples from
      22 pediatric and 22 adult HCV patients were analyzed. Histological parameters
      were evaluated. On serum TGF-beta1, tissue inhibitor of matrix metalloprotein
      inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of
      procollagen type III (PIIINP) were tested. RESULTS: Significant fibrosis (F>=2)
      and advanced fibrosis (F>=3) represented 64% and 20%, respectively in children;
      while 54% F>=2 and 23% F>=3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p
      = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1
      (p = 0.039) just in children; but TGF-beta1 was associated with mild fibrosis (p
      = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced
      fibrosis was 0.800 (95%IC 0.598-0.932). In adults, the best AUROCs were that of
      HA, PIIINP and TGF-beta1 [0.929 (IC95% 0.736-0.994), 0.894 (IC95% 0.689-0.984)
      and 0.835 (IC95% 0.617-0.957)], respectively. In children, according to the cut
      off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72%
      (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 ug/L), and TGF
      beta1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult
      patients by using HA and 73% (16/22) using PIIINP or TGF-beta1. CONCLUSIONS: In
      adults given the diagnostic accuracy of HA, PIIINP, TGF-beta1, their combination
      may provide a potential useful tool to assess liver fibrosis. This first
      pediatric study suggests that TIMP-1 is clinically useful for predicting liver
      fibrosis in HCV patients.

PMID- 21858036
TI  - The influence of Staphylococcus aureus on gut microbial ecology in an in vitro
      continuous culture human colonic model system.
AB  - An anaerobic three-stage continuous culture model of the human colon (gut model),
      which represent different anatomical areas of the large intestine, was used to
      study the effect of S. aureus infection of the gut on the resident faecal
      microbiota. Studies on the development of the microbiota in the three vessels
      were performed and bacteria identified by culture independent fluorescence in
      situ hybridization (FISH). Furthermore, short chain fatty acids (SCFA), as
      principal end products of gut bacterial metabolism, were measured along with a
      quantitative assessment of the predominant microbiota. During steady state
      conditions, numbers of S. aureus cells stabilised until they were washed out, but
      populations of indigenous bacteria were transiently altered; thus S. aureus was
      able to compromise colonisation resistance by the colonic microbiota.
      Furthermore, the concentration of butyric acid in the vessel representing the
      proximal colon was significantly decreased by infection. Thus infection by S.
      aureus appears to be able to alter the overall structure of the human colonic
      microbiota and the microbial metabolic profiles. This work provides an initial in
      vitro model to analyse interactions with pathogens.

PMID- 21858037
TI  - Quantitative expression profile of distinct functional regions in the adult mouse
      brain.
AB  - The adult mammalian brain is composed of distinct regions with specialized roles
      including regulation of circadian clocks, feeding, sleep/awake, and seasonal
      rhythms. To find quantitative differences of expression among such various brain
      regions, we conducted the BrainStars (B*) project, in which we profiled the
      genome-wide expression of ~50 small brain regions, including sensory centers, and
      centers for motion, time, memory, fear, and feeding. To avoid confounds from
      temporal differences in gene expression, we sampled each region every 4 hours for
      24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused
      on spatial differences in gene expression. We used informatics to identify
      candidate genes with expression changes showing high or low expression in
      specific regions. We also identified candidate genes with stable expression
      across brain regions that can be used as new internal control genes, and ligand
      receptor interactions of neurohormones and neurotransmitters. Through these
      analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates
      for 44 small brain regions, 915 internal control gene candidates, and 23,864
      inferred ligand-receptor interactions. We also found that these sets include well
      known genes as well as novel candidate genes that might be related to specific
      functions in brain regions. We used our findings to develop an integrated
      database (http://brainstars.org/) for exploring genome-wide expression in the
      adult mouse brain, and have made this database openly accessible. These new
      resources will help accelerate the functional analysis of the mammalian brain and
      the elucidation of its regulatory network systems.

PMID- 21858038
TI  - TIG3 tumor suppressor-dependent organelle redistribution and apoptosis in skin
      cancer cells.
AB  - TIG3 is a tumor suppressor protein that limits keratinocyte survival during
      normal differentiation. It is also important in cancer, as TIG3 level is reduced
      in tumors and in skin cancer cell lines, suggesting that loss of expression may
      be required for cancer cell survival. An important goal is identifying how TIG3
      limits cell survival. In the present study we show that TIG3 expression in
      epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and
      promotes morphological and biochemical apoptosis. To identify the mechanism that
      drives these changes, we demonstrate that TIG3 localizes near the centrosome and
      that pericentrosomal accumulation of TIG3 alters microtubule and microfilament
      organization and organelle distribution. Organelle accumulation at the centrosome
      is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal
      organelle accumulation. These changes are associated with reduced cyclin D1,
      cyclin E and cyclin A, and increased p21 level. In addition, Bax level is
      increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9
      and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a
      key event that results in microtubule and microfilament redistribution and
      pericentrosomal organelle clustering and that leads to cancer cell apoptosis.

PMID- 21858039
TI  - Systematic targeted integration to study Albumin gene control elements.
AB  - To study transcriptional regulation by distant enhancers, we devised a system of
      easily modified reporter plasmids for integration into single-copy targeting
      cassettes in clones of HuH7, a human hepatocellular carcinoma. The plasmid
      constructs tested transcriptional function of a 35-kb region that contained the
      rat albumin gene and its upstream flanking region. Expression of integrants was
      analyzed in two orientations, and compared to transient expression of non
      integrated plasmids. Enhancers were studied in their natural positions relative
      to the promoter and localized by deletion. All constructs were also analyzed by
      transient transfection assays. In addition to the known albumin gene enhancer (E1
      at -10 kb), we demonstrated two new enhancers, E2 at -13, and E4 at +1.2 kb. All
      three enhancers functioned in both transient assays and integrated constructs.
      However, chromosomal integration demonstrated several differences from transient
      expression. For example, analysis of E2 showed that enhancer function within the
      chromosome required a larger gene region than in transient assays. Another
      conserved region, E3 at -0.7 kb, functioned as an enhancer in transient assays
      but inhibited the function of E1 and E2 when chromosomally integrated. The
      enhancers did not show additive or synergistic behavior,an effect consistent with
      competition for the promoter or inhibitory interactions among enhancers. Growth
      arrest by serum starvation strongly stimulated the function of some integrated
      enhancers, consistent with the expected disruption of enhancer-promoter looping
      during the cell cycle.

PMID- 21858040
TI  - Comparison of the safety and pharmacokinetics of ST-246(r) after i.v. infusion or
      oral administration in mice, rabbits and monkeys.
AB  - BACKGROUND: ST-246(r) is an antiviral, orally bioavailable small molecule in
      clinical development for treatment of orthopoxvirus infections. An intravenous
      (i.v.) formulation may be required for some hospitalized patients who are unable
      to take oral medication. An i.v. formulation has been evaluated in three species
      previously used in evaluation of both efficacy and toxicology of the oral
      formulation. METHODOLOGY/PRINCIPAL FINDINGS: The pharmacokinetics of ST-246 after
      i.v. infusions in mice, rabbits and nonhuman primates (NHP) were compared to
      those obtained after oral administration. Ten minute i.v. infusions of ST-246 at
      doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations
      ranging from 16.9 to 238 ug/mL. Elimination appeared predominately first-order
      and exposure dose-proportional up to 30 mg/kg. Short i.v. infusions (5 to 15
      minutes) in rabbits resulted in rapid distribution followed by slower
      elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30
      mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The
      pharmacokinetics and tolerability for the two highest doses were evaluated when
      administered as two equivalent 4 hour infusions initiated 12 hours apart.
      Terminal elimination half-lives in all species for oral and i.v. infusions were
      similar. Dose-limiting central nervous system effects were identified in all
      three species and appeared related to high C(max) plasma concentrations. These
      effects were eliminated using slower i.v. infusions. CONCLUSIONS/SIGNIFICANCE:
      Pharmacokinetic profiles after i.v. infusion compared to those observed after
      oral administration demonstrated the necessity of longer i.v. infusions to (1)
      mimic the plasma exposure observed after oral administration and (2) avoid C(max)
      associated toxicity. Shorter infusions at higher doses in NHP resulted in
      decreased clearance, suggesting saturated distribution or elimination.
      Elimination half-lives in all species were similar between oral and i.v.
      administration. The administration of ST-246 was well tolerated as a slow i.v.
      infusion.

PMID- 21858041
TI  - Dramatic transcriptional changes in an intracellular parasite enable host
      switching between plant and insect.
AB  - Phytoplasmas are bacterial plant pathogens that have devastating effects on the
      yields of crops and plants worldwide. They are intracellular parasites of both
      plants and insects, and are spread among plants by insects. How phytoplasmas can
      adapt to two diverse environments is of considerable interest; however, the
      mechanisms enabling the "host switching" between plant and insect hosts are
      poorly understood. Here, we report that phytoplasmas dramatically alter their
      gene expression in response to "host switching" between plant and insect. We
      performed a detailed characterization of the dramatic change that occurs in the
      gene expression profile of Candidatus Phytoplasma asteris OY-M strain
      (approximately 33% of the genes change) upon host switching between plant and
      insect. The phytoplasma may use transporters, secreted proteins, and metabolic
      enzymes in a host-specific manner. As phytoplasmas reside within the host cell,
      the proteins secreted from phytoplasmas are thought to play crucial roles in the
      interplay between phytoplasmas and host cells. Our microarray analysis revealed
      that the expression of the gene encoding the secreted protein PAM486 was highly
      upregulated in the plant host, which is also observed by immunohistochemical
      analysis, suggesting that this protein functions mainly when the phytoplasma
      grows in the plant host. Additionally, phytoplasma growth in planta was partially
      suppressed by an inhibitor of the MscL osmotic channel that is highly expressed
      in the plant host, suggesting that the osmotic channel might play an important
      role in survival in the plant host. These results also suggest that the
      elucidation of "host switching" mechanism may contribute to the development of
      novel pest controls.

PMID- 21858042
TI  - Structural analysis of the essential resuscitation promoting factor YeaZ suggests
      a mechanism of nucleotide regulation through dimer reorganization.
AB  - BACKGROUND: The yeaZ gene product forms part of the conserved network
      YjeE/YeaZ/YgjD essential for the survival of many gram-negative eubacteria. Among
      other as yet unidentified roles, YeaZ functions as a resuscitation promoting
      factor required for survival and resuscitation of cells in a viable but non
      culturable (VBNC) state. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate
      in detail the structure/function relationship of this family of proteins we have
      performed X-ray crystallographic studies of Vibrio parahaemolyticus YeaZ. The
      YeaZ structure showed that it has a classic actin-like nucleotide-binding fold.
      Comparisons of this crystal structure to that of available homologues from E.
      coli, T. maritima and S. typhimurium revealed two distinctly different modes of
      dimer formation. In one form, prevalent in the absence of nucleotide, the
      putative nucleotide-binding site is incomplete, lacking a binding pocket for a
      nucleotide base. In the second form, residues from the second subunit complete
      the nucleotide-binding site. This suggests that the two dimer architectures
      observed in the crystal structures correspond to a free and a nucleotide-bound
      form of YeaZ. A multiple sequence alignment of YeaZ proteins from different
      bacteria allowed us to identify a large conserved hydrophobic patch on the
      protein surface that becomes exposed upon nucleotide-driven dimer re-arrangement.
      We hypothesize that the transition between two dimer architectures represents the
      transition between the 'on' and 'off' states of YeaZ. The effect of this
      transition is to alternately expose and bury a docking site for the partner
      protein YgjD. CONCLUSIONS/SIGNIFICANCE: This paper provides the first structural
      insight into the putative mechanism of nucleotide regulation of YeaZ through
      dimer reorganization. Our analysis suggests that nucleotide binding to YeaZ may
      act as a regulator or switch that changes YeaZ shape, allowing it to switch
      partners between YjeE and YgjD.

PMID- 21858043
TI  - The kinase inhibitor SFV785 dislocates dengue virus envelope protein from the
      replication complex and blocks virus assembly.
AB  - Dengue virus (DENV) is the etiologic agent for dengue fever, for which there is
      no approved vaccine or specific anti-viral drug. As a remedy for this, we
      explored the use of compounds that interfere with the action of required host
      factors and describe here the characterization of a kinase inhibitor (SFV785),
      which has selective effects on NTRK1 and MAPKAPK5 kinase activity, and anti-viral
      activity on Hepatitis C, DENV and yellow fever viruses. SFV785 inhibited DENV
      propagation without inhibiting DENV RNA synthesis or translation. The compound
      did not cause any changes in the cellular distribution of non-structural 3, a
      protein critical for DENV RNA synthesis, but altered the distribution of the
      structural envelope protein from a reticulate network to enlarged discrete
      vesicles, which altered the co-localization with the DENV replication complex.
      Ultrastructural electron microscopy analyses of DENV-infected SFV785-treated
      cells showed the presence of viral particles that were distinctly different from
      viable enveloped virions within enlarged ER cisternae. These viral particles were
      devoid of the dense nucleocapsid. The secretion of the viral particles was not
      inhibited by SFV785, however a reduction in the amount of secreted infectious
      virions, DENV RNA and capsid were observed. Collectively, these observations
      suggest that SFV785 inhibited the recruitment and assembly of the nucleocapsid in
      specific ER compartments during the DENV assembly process and hence the
      production of infectious DENV. SFV785 and derivative compounds could be useful
      biochemical probes to explore the DENV lifecycle and could also represent a new
      class of anti-virals.

PMID- 21858044
TI  - Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is
      associated with carotid intima-medial thickness.
AB  - OBJECTIVE: The combined thickness of the intima and media of the carotid artery
      (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease
      and stroke. Previous studies indicate that carotid intima-medial thickness is a
      significantly heritable phenotype, but the responsible genes are largely unknown.
      Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity
      regulates corticosteroid metabolism in the liver and adipose tissue; variability
      in measures of corticosteroid metabolism within the normal range have been
      associated with risk factors for cardiovascular disease. We performed a genetic
      association study in 854 members of 224 families to assess the relationship
      between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase
      (H6PD) and carotid intima-medial thickness. METHODS: Families were ascertained
      via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single
      nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were
      genotyped. Association was assessed following adjustment for significant
      covariates including "classical" cardiovascular risk factors. Functional studies
      to determine the effect of particular SNPs on H6PDH were performed. RESULTS:
      There was evidence of association between the single nucleotide polymorphism
      rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from
      proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness
      (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid
      intima-medial thickness measurement per allele, and determined 2% of the
      population variability in the phenotype. CONCLUSIONS: Our results suggest a novel
      role for the H6PD gene in atherosclerosis susceptibility.

PMID- 21858045
TI  - Transcriptomic analysis brings new insight into the biological role of the prion
      protein during mouse embryogenesis.
AB  - The biological function of the Prion protein remains largely unknown but recent
      data revealed its implication in early zebrafish and mammalian embryogenesis. To
      gain further insight into its biological function, comparative transcriptomic
      analysis between FVB/N and FVB/N Prnp knockout mice was performed at early
      embryonic stages. RNAseq analysis revealed the differential expression of 73 and
      263 genes at E6.5 and E7.5, respectively. The related metabolic pathways
      identified in this analysis partially overlap with those described in PrP1 and
      PrP2 knockdown zebrafish embryos and prion-infected mammalian brains and
      emphasize a potentially important role for the PrP family genes in early
      developmental processes.

PMID- 21858046
TI  - Achieving conservation when opportunity costs are high: optimizing reserve design
      in Alberta's oil sands region.
AB  - Recent studies have shown that conservation gains can be achieved when the
      spatial distributions of biological benefits and economic costs are incorporated
      in the conservation planning process. Using Alberta, Canada, as a case study we
      apply these techniques in the context of coarse-filter reserve design. Because
      targets for ecosystem representation and other coarse-filter design elements are
      difficult to define objectively we use a trade-off analysis to systematically
      explore the relationship between conservation targets and economic opportunity
      costs. We use the Marxan conservation planning software to generate reserve
      designs at each level of conservation target to ensure that our quantification of
      conservation and economic outcomes represents the optimal allocation of resources
      in each case. Opportunity cost is most affected by the ecological representation
      target and this relationship is nonlinear. Although petroleum resources are
      present throughout most of Alberta, and include highly valuable oil sands
      deposits, our analysis indicates that over 30% of public lands could be protected
      while maintaining access to more than 97% of the value of the region's resources.
      Our case study demonstrates that optimal resource allocation can be usefully
      employed to support strategic decision making in the context of land-use
      planning, even when conservation targets are not well defined.

PMID- 21858047
TI  - Reconstitution of the costunolide biosynthetic pathway in yeast and Nicotiana
      benthamiana.
AB  - The sesquiterpene costunolide has a broad range of biological activities and is
      the parent compound for many other biologically active sesquiterpenes such as
      parthenolide. Two enzymes of the pathway leading to costunolide have been
      previously characterized: germacrene A synthase (GAS) and germacrene A oxidase
      (GAO), which together catalyse the biosynthesis of germacra-1(10),4,11(13)-trien
      12-oic acid. However, the gene responsible for the last step toward costunolide
      has not been characterized until now. Here we show that chicory costunolide
      synthase (CiCOS), CYP71BL3, can catalyse the oxidation of germacra-1(10),4,11(13)
      trien-12-oic acid to yield costunolide. Co-expression of feverfew GAS (TpGAS),
      chicory GAO (CiGAO), and chicory COS (CiCOS) in yeast resulted in the
      biosynthesis of costunolide. The catalytic activity of TpGAS, CiGAO and CiCOS was
      also verified in planta by transient expression in Nicotiana benthamiana.
      Mitochondrial targeting of TpGAS resulted in a significant increase in the
      production of germacrene A compared with the native cytosolic targeting. When the
      N. benthamiana leaves were co-infiltrated with TpGAS and CiGAO, germacrene A
      almost completely disappeared as a result of the presence of CiGAO. Transient
      expression of TpGAS, CiGAO and CiCOS in N. benthamiana leaves resulted in
      costunolide production of up to 60 ng.g(-1) FW. In addition, two new compounds
      were formed that were identified as costunolide-glutathione and costunolide
      cysteine conjugates.

PMID- 21858048
TI  - Development of immune-specific interaction potentials and their application in
      the multi-agent-system VaccImm.
AB  - Peptide vaccination in cancer therapy is a promising alternative to conventional
      methods. However, the parameters for this personalized treatment are difficult to
      access experimentally. In this respect, in silico models can help to narrow down
      the parameter space or to explain certain phenomena at a systems level. Herein,
      we develop two empirical interaction potentials specific to B-cell and T-cell
      receptor complexes and validate their applicability in comparison to a more
      general potential. The interaction potentials are applied to the model VaccImm
      which simulates the immune response against solid tumors under peptide
      vaccination therapy. This multi-agent system is derived from another immune
      system simulator (C-ImmSim) and now includes a module that enables the amino acid
      sequence of immune receptors and their ligands to be taken into account. The
      multi-agent approach is combined with approved methods for prediction of major
      histocompatibility complex (MHC)-binding peptides and the newly developed
      interaction potentials. In the analysis, we critically assess the impact of the
      different modules on the simulation with VaccImm and how they influence each
      other. In addition, we explore the reasons for failures in inducing an immune
      response by examining the activation states of the immune cell populations in
      detail.In summary, the present work introduces immune-specific interaction
      potentials and their application to the agent-based model VaccImm which simulates
      peptide vaccination in cancer therapy.

PMID- 21858050
TI  - Adverse effects of simulated hyper- and hypo-phosphatemia on endothelial cell
      function and viability.
AB  - BACKGROUND: Dysregulation of phosphate homeostasis as occurs in chronic kidney
      disease is associated with cardiovascular complications. It has been suggested
      that both hyperphosphatemia and hypophosphatemia can cause cardiovascular
      disease. The molecular mechanisms by which high or low serum phosphate levels
      adversely affect cardiovascular function are poorly understood. The purpose of
      this study was to explore the mechanisms of endothelial dysfunction in the
      presence of non-physiologic phosphate levels. METHODOLOGY/PRINCIPAL FINDINGS: We
      studied the effects of simulated hyper- and hypophosphatemia in human umbilical
      vein endothelial cells in vitro. We found both simulated hyperphosphatemia and
      hypophosphatemia decrease eNOS expression and NO production. This was associated
      with reduced intracellular calcium, increased protein kinase C beta2 (PKCbeta2),
      reduced cell viability, and increased apoptosis. While simulated
      hyperphosphatemia was associated with decreased Akt/p-Akt, Bcl-xl/Bax ratios,
      NFkB-p65 and p-Erk abundance, simulated hypophosphatemia was associated with
      increased Akt/p-Akt and Bcl-xl/Bax ratios and p-Mek, p38, and p-p38 abundance.
      CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of endothelial
      dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia
      and hypophosphatemia decrease eNOS activity via reduced intracellular calcium and
      increased PKCbeta2. Hyperphosphatemia also appears to reduce eNOS transcription
      via reduced signaling through PI3K/Akt/NF-kB and MAPK/NF-kB pathways. On the
      other hand, hypophosphatemia appears to activate these pathways. Our data
      provides the basis for further studies to elucidate the relationship between
      altered phosphate homeostasis and cardiovascular disease. As a corollary, our
      data suggests that the level of phosphate in the culture media, if not in the
      physiologic range, may inadvertently affect experimental results.

PMID- 21858049
TI  - Comparison of microbial community compositions of injection and production well
      samples in a long-term water-flooded petroleum reservoir.
AB  - Water flooding plays an important role in recovering oil from depleted petroleum
      reservoirs. Exactly how the microbial communities of production wells are
      affected by microorganisms introduced with injected water has previously not been
      adequately studied. Using denaturing gradient gel electrophoresis (DGGE) approach
      and 16S rRNA gene clone library analysis, the comparison of microbial communities
      is carried out between one injection water and two production waters collected
      from a working block of the water-flooded Gudao petroleum reservoir located in
      the Yellow River Delta. DGGE fingerprints showed that the similarities of the
      bacterial communities between the injection water and production waters were
      lower than between the two production waters. It was also observed that the
      archaeal composition among these three samples showed no significant difference.
      Analysis of the 16S rRNA gene clone libraries showed that the dominant groups
      within the injection water were Betaproteobacteria, Gammaproteobacteria and
      Methanomicrobia, while the dominant groups in the production waters were
      Gammaproteobacteria and Methanobacteria. Only 2 out of 54 bacterial operational
      taxonomic units (OTUs) and 5 out of 17 archaeal OTUs in the injection water were
      detected in the production waters, indicating that most of the microorganisms
      introduced by the injection water may not survive to be detected in the
      production waters. Additionally, there were 55.6% and 82.6% unique OTUs in the
      two production waters respectively, suggesting that each production well has its
      specific microbial composition, despite both wells being flooded with the same
      injection water.

PMID- 21858051
TI  - Combining dynamic stretch and tunable stiffness to probe cell mechanobiology in
      vitro.
AB  - Cells have the ability to actively sense their mechanical environment and respond
      to both substrate stiffness and stretch by altering their adhesion,
      proliferation, locomotion, morphology, and synthetic profile. In order to
      elucidate the interrelated effects of different mechanical stimuli on cell
      phenotype in vitro, we have developed a method for culturing mammalian cells in a
      two-dimensional environment at a wide range of combined levels of substrate
      stiffness and dynamic stretch. Polyacrylamide gels were covalently bonded to
      flexible silicone culture plates and coated with monomeric collagen for cell
      adhesion. Substrate stiffness was adjusted from relatively soft (G' = 0.3 kPa) to
      stiff (G' = 50 kPa) by altering the ratio of acrylamide to bis-acrylamide, and
      the silicone membranes were stretched over circular loading posts by applying
      vacuum pressure to impart near-uniform stretch, as confirmed by strain field
      analysis. As a demonstration of the system, porcine aortic valve interstitial
      cells (VIC) and human mesenchymal stem cells (hMSC) were plated on soft and stiff
      substrates either statically cultured or exposed to 10% equibiaxial or pure
      uniaxial stretch at 1 Hz for 6 hours. In all cases, cell attachment and cell
      viability were high. On soft substrates, VICs cultured statically exhibit a small
      rounded morphology, significantly smaller than on stiff substrates (p<0.05).
      Following equibiaxial cyclic stretch, VICs spread to the extent of cells cultured
      on stiff substrates, but did not reorient in response to uniaxial stretch to the
      extent of cells stretched on stiff substrates. hMSCs exhibited a less pronounced
      response than VICs, likely due to a lower stiffness threshold for spreading on
      static gels. These preliminary data demonstrate that inhibition of spreading due
      to a lack of matrix stiffness surrounding a cell may be overcome by externally
      applied stretch suggesting similar mechanotransduction mechanisms for sensing
      stiffness and stretch.

PMID- 21858052
TI  - Synaptic connections of the neurokinin 1 receptor-like immunoreactive neurons in
      the rat medullary dorsal horn.
AB  - The synaptic connections between neurokinin 1 (NK1) receptor-like immunoreactive
      (LI) neurons and gamma-aminobutyric acid (GABA)-, glycine (Gly)-, serotonin (5
      HT)- or dopamine-beta-hydroxylase (DBH, a specific marker for norepinephrinergic
      neuronal structures)-LI axon terminals in the rat medullary dorsal horn (MDH)
      were examined under electron microscope by using a pre-embedding
      immunohistochemical double-staining technique. NK1 receptor-LI neurons were
      observed principally in laminae I and III, only a few of them were found in
      lamina II of the MDH. GABA-, Gly-, 5-HT-, or DBH-LI axon terminals were densely
      encountered in laminae I and II, and sparsely in lamina III of the MDH. Some of
      these GABA-, Gly-, 5-HT-, or DBH-LI axon terminals were observed to make
      principally symmetric synapses with NK1 receptor-LI neuronal cell bodies and
      dendritic processes in laminae I, II and III of the MDH. The present results
      suggest that neurons expressing NK1 receptor within the MDH might be modulated by
      GABAergic and glycinergic inhibitory intrinsic neurons located in the MDH and 5
      HT- or norepinephrine (NE)-containing descending fibers originated from
      structures in the brainstem.

PMID- 21858053
TI  - Predator cat odors activate sexual arousal pathways in brains of Toxoplasma
      gondii infected rats.
AB  - Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at
      first exposure, a presumed response to the evolutionary pressures of predation.
      Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the
      cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat
      to sexually reproduce, this change in host behavior is thought to be a remarkable
      example of a parasite manipulating a mammalian host for its own benefit.
      Toxoplasma does not influence host response to non-feline predator odor nor does
      it alter behavior on olfactory, social, fear or anxiety tests, arguing for
      specific manipulation in the processing of cat odor. We report that Toxoplasma
      infection alters neural activity in limbic brain areas necessary for innate
      defensive behavior in response to cat odor. Moreover, Toxoplasma increases
      activity in nearby limbic regions of sexual attraction when the rat is exposed to
      cat urine, compelling evidence that Toxoplasma overwhelms the innate fear
      response by causing, in its stead, a type of sexual attraction to the normally
      aversive cat odor.

PMID- 21858054
TI  - Probiotic-derived polyphosphate enhances the epithelial barrier function and
      maintains intestinal homeostasis through integrin-p38 MAPK pathway.
AB  - Probiotics exhibit beneficial effects on human health, particularly in the
      maintenance of intestinal homeostasis in a complex manner notwithstanding the
      diversity of an intestinal flora between individuals. Thus, it is highly probable
      that some common molecules secreted by probiotic and/or commensal bacteria
      contribute to the maintenance of intestinal homeostasis and protect the
      intestinal epithelium from injurious stimuli. To address this question, we aimed
      to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus
      brevis SBC8803 which possess the ability to induce cytoprotective heat shock
      proteins in mouse small intestine. L. brevis was incubated in MRS broth and the
      supernatant was passed through with a 0.2-um filter. Caco2/bbe cells were treated
      with the culture supernatant, and HSP27 expression was evaluated by Western
      blotting. HSP27-inducible components were separated by ammonium sulfate
      precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC.
      Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly
      P), a simple repeated structure of phosphates, which is a common product of
      lactobacilli and other bacteria associated with intestinal microflora without any
      definitive physiological functions. Then, poly P was synthesized by poly P
      synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly
      induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant
      induced intestinal permeability in the mouse small intestine and pharmacological
      inhibitors of p38 MAPK and integrins counteract its protective effect. Daily
      intrarectal administration of poly P (10 ug) improved the inflammation grade and
      survival rate in 4% sodium dextran sulfate-administered mice. This study, for the
      first time, demonstrated that poly P is the molecule responsible for maintaining
      intestinal barrier actions which are mediated through the intestinal integrin
      beta1-p38 MAPK.

PMID- 21858055
TI  - Aquarium nitrification revisited: Thaumarchaeota are the dominant ammonia
      oxidizers in freshwater aquarium biofilters.
AB  - Ammonia-oxidizing archaea (AOA) outnumber ammonia-oxidizing bacteria (AOB) in
      many terrestrial and aquatic environments. Although nitrification is the primary
      function of aquarium biofilters, very few studies have investigated the
      microorganisms responsible for this process in aquaria. This study used
      quantitative real-time PCR (qPCR) to quantify the ammonia monooxygenase (amoA)
      and 16S rRNA genes of Bacteria and Thaumarchaeota in freshwater aquarium
      biofilters, in addition to assessing the diversity of AOA amoA genes by
      denaturing gradient gel electrophoresis (DGGE) and clone libraries. AOA were
      numerically dominant in 23 of 27 freshwater biofilters, and in 12 of these
      biofilters AOA contributed all detectable amoA genes. Eight saltwater aquaria and
      two commercial aquarium nitrifier supplements were included for comparison. Both
      thaumarchaeal and bacterial amoA genes were detected in all saltwater samples,
      with AOA genes outnumbering AOB genes in five of eight biofilters. Bacterial amoA
      genes were abundant in both supplements, but thaumarchaeal amoA and 16S rRNA
      genes could not be detected. For freshwater aquaria, the proportion of amoA genes
      from AOA relative to AOB was inversely correlated with ammonium concentration.
      DGGE of AOA amoA genes revealed variable diversity across samples, with nonmetric
      multidimensional scaling (NMDS) indicating separation of freshwater and saltwater
      fingerprints. Composite clone libraries of AOA amoA genes revealed distinct
      freshwater and saltwater clusters, as well as mixed clusters containing both
      freshwater and saltwater amoA gene sequences. These results reveal insight into
      commonplace residential biofilters and suggest that aquarium biofilters may
      represent valuable biofilm microcosms for future studies of AOA ecology.

PMID- 21858056
TI  - Tumor-initiating cells are enriched in CD44(hi) population in murine salivary
      gland tumor.
AB  - Tumor-initiating cells (T-ICs) discovered in various tumors have been widely
      reported. However, T-IC populations in salivary gland tumors have yet to be
      elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic
      mouse model of a salivary gland tumor, we identified CD44(high) (CD44(hi)) tumor
      cells, characterized by high levels of CD44 cell surface expression, as the T-ICs
      for pleomorphic adenomas. These CD44(hi) tumor cells incorporated 5-bromo-2
      deoxyuridine (BrdU), at a lower rate than their CD44(negative) (CD44(neg))
      counterparts, and also retained BrdU for a long period of time. Cell surface
      maker analysis revealed that 25% of the CD44(hi) tumor cells co-express other
      cancer stem cell markers such as CD133 and CD117. As few as 500 CD44(hi) tumor
      cells were sufficient to initiate pleomorphic adenomas in one third of the
      wildtype mice, whereas more than 1*10(4) CD44(neg) cells were needed for the same
      purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription
      of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81-96 in
      the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our
      results establish the existence of T-ICs in murine salivary gland tumors, and
      suggest a potential molecular mechanism for CD44 upregulation.

PMID- 21858057
TI  - Line tension and stability of domains in cell-adhesion zones mediated by long and
      short receptor-ligand complexes.
AB  - Submicron scale domains of membrane-anchored receptors play an important role in
      cell signaling. Central questions concern the stability of these microdomains,
      and the mechanisms leading to the domain formation. In immune-cell adhesion
      zones, microdomains of short receptor-ligand complexes form next to domains of
      significantly longer receptor-ligand complexes. The length mismatch between the
      receptor-ligand complexes leads to membrane deformations and has been suggested
      as a possible cause of the domain formation. The domain formation is a nucleation
      and growth process that depends on the line tension and free energy of the
      domains. Using a combination of analytical calculations and Monte Carlo
      simulations, we derive here general expressions for the line tension between
      domains of long and short receptor-ligand complexes and for the adhesion free
      energy of the domains. We argue that the length mismatch of receptor-ligand
      complexes alone is sufficient to drive the domain formation, and obtain submicron
      scale minimum sizes for stable domains that are consistent with the domain sizes
      observed during immune-cell adhesion.

PMID- 21858058
TI  - Identification of bacteria in blood culture broths using matrix-assisted laser
      desorption-ionization SepsityperTM and time of flight mass spectrometry.
AB  - Matrix-assisted laser desorption ionization time of flight mass spectrometry
      (MALDI-TOF MS) is a novel method for the direct identification of bacteria from
      blood culture broths. We evaluate for the first time, the performance of the
      MALDI SepsityperTM Kit and MS for the identification of bacteria compared to
      standard phenotypic methods using the manufacturer's specified bacterial
      identification criteria (spectral scores >=1.700-1.999 and >=2.000 indicated
      identification to genus and species level, respectively). Five hundred and seven
      positive blood culture broths were prospectively examined, of which 379 (74.8%;
      358 monomicrobial, 21 polymicrobial) were identified by MALDI-TOF MS; 195 (100%)
      and 132 (67.7%) of 195 gram-positive; and 163 (100%) and 149 (91.4%) of 163 gram
      negative organisms from monomicrobial blood cultures were correctly identified to
      genus and species level, respectively. Spectral scores <1.700 (no identification)
      were obtained in 128/507 (25.2%) positive blood culture broths, including 31.6%
      and 32.3% of gram-positive and polymicrobial blood cultures, respectively.
      Significantly more gram-negative organisms were identified compared to gram
      positive organisms at species level (p<0.0001). Five blood cultures were
      misidentified, but at species level only; including four monomicrobial blood
      cultures with Streptococcus oralis/mitis that were misidentified as Streptococcus
      pneumoniae. Positive predictive values for the direct identification of both gram
      positive and gram-negative bacteria from monomicrobial blood culture broths to
      genus level were 100%. A diagnostic algorithm for positive blood culture broths
      that incorporates gram staining and MALDI-TOF MS should identify the majority of
      pathogens, particularly to genus level.

PMID- 21858059
TI  - HIV protein sequence hotspots for crosstalk with host hub proteins.
AB  - HIV proteins target host hub proteins for transient binding interactions. The
      presence of viral proteins in the infected cell results in out-competition of
      host proteins in their interaction with hub proteins, drastically affecting cell
      physiology. Functional genomics and interactome datasets can be used to quantify
      the sequence hotspots on the HIV proteome mediating interactions with host hub
      proteins. In this study, we used the HIV and human interactome databases to
      identify HIV targeted host hub proteins and their host binding partners (H2). We
      developed a high throughput computational procedure utilizing motif discovery
      algorithms on sets of protein sequences, including sequences of HIV and H2
      proteins. We identified as HIV sequence hotspots those linear motifs that are
      highly conserved on HIV sequences and at the same time have a statistically
      enriched presence on the sequences of H2 proteins. The HIV protein motifs
      discovered in this study are expressed by subsets of H2 host proteins potentially
      outcompeted by HIV proteins. A large subset of these motifs is involved in
      cleavage, nuclear localization, phosphorylation, and transcription factor binding
      events. Many such motifs are clustered on an HIV sequence in the form of
      hotspots. The sequential positions of these hotspots are consistent with the
      curated literature on phenotype altering residue mutations, as well as with
      existing binding site data. The hotspot map produced in this study is the first
      global portrayal of HIV motifs involved in altering the host protein network at
      highly connected hub nodes.

PMID- 21858060
TI  - Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity.
AB  - BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD-dependent deacetylases and/or
      ADP-ribosyltransferases that are involved in metabolism, stress responses and
      longevity. SIRT3 is localized to mitochondria, where it deacetylates and
      activates a number of enzymes involved in fuel oxidation and energy production.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed a proteomic screen to
      identify SIRT3 interacting proteins and identified several subunits of complex II
      and V of the electron transport chain. Two subunits of complex II (also known as
      succinate dehydrogenase, or SDH), SDHA and SDHB, interacted specifically with
      SIRT3. Using mass spectrometry, we identified 13 acetylation sites on SDHA,
      including six novel acetylated residues. SDHA is hyperacetylated in SIRT3 KO mice
      and SIRT3 directly deacetylates SDHA in a NAD-dependent manner. Finally, we found
      that SIRT3 regulates SDH activity both in cells and in murine brown adipose
      tissue. CONCLUSIONS/SIGNIFICANCE: Our study identifies SDHA as a binding partner
      and substrate for SIRT3 deacetylase activity. SIRT3 loss results in decreased SDH
      enzyme activity, suggesting that SIRT3 may be an important physiological
      regulator of SDH activity.

PMID- 21858061
TI  - Geographic variation in advertisement calls in a tree frog species: gene flow and
      selection hypotheses.
AB  - BACKGROUND: In a species with a large distribution relative to its dispersal
      capacity, geographic variation in traits may be explained by gene flow,
      selection, or the combined effects of both. Studies of genetic diversity using
      neutral molecular markers show that patterns of isolation by distance (IBD) or
      barrier effect may be evident for geographic variation at the molecular level in
      amphibian species. However, selective factors such as habitat, predator, or
      interspecific interactions may be critical for geographic variation in sexual
      traits. We studied geographic variation in advertisement calls in the tree frog
      Hyla japonica to understand patterns of variation in these traits across Korea
      and provide clues about the underlying forces for variation. METHODOLOGY: We
      recorded calls of H. japonica in three breeding seasons from 17 localities
      including localities in remote Jeju Island. Call characters analyzed were note
      repetition rate (NRR), note duration (ND), and dominant frequency (DF), along
      with snout-to-vent length. RESULTS: The findings of a barrier effect on DF and a
      longitudinal variation in NRR seemed to suggest that an open sea between the
      mainland and Jeju Island and mountain ranges dominated by the north-south Taebaek
      Mountains were related to geographic variation in call characters. Furthermore,
      there was a pattern of IBD in mitochondrial DNA sequences. However, no comparable
      pattern of IBD was found between geographic distance and call characters. We also
      failed to detect any effects of habitat or interspecific interaction on call
      characters. CONCLUSIONS: Geographic variations in call characters as well as
      mitochondrial DNA sequences were largely stratified by geographic factors such as
      distance and barriers in Korean populations of H. japonica. Although we did not
      detect effects of habitat or interspecific interaction, some other selective
      factors such as sexual selection might still be operating on call characters in
      conjunction with restricted gene flow.

PMID- 21858062
TI  - Analysis of variance in neuroreceptor ligand imaging studies.
AB  - Radioligand positron emission tomography (PET) with dual scan paradigms can
      provide valuable insight into changes in synaptic neurotransmitter concentration
      due to experimental manipulation. The residual t-test has been utilized to
      improve the sensitivity of the t-test in PET studies. However, no further
      development of statistical tests using residuals has been proposed so far to be
      applied in cases when there are more than two conditions. Here, we propose the
      residual f-test, a one-way analysis of variance (ANOVA), and examine its
      feasibility using simulated [(11)C]raclopride PET data. We also re-visit data
      from our previously published [(11)C]raclopride PET study, in which 10
      individuals underwent three PET scans under different conditions. We found that
      the residual f-test is superior in terms of sensitivity than the conventional f
      test while still controlling for type 1 error. The test will therefore allow us
      to reliably test hypotheses in the smaller sample sizes often used in explorative
      PET studies.

PMID- 21858063
TI  - Including total EGFR staining in scoring improves EGFR mutations detection by
      mutation-specific antibodies and EGFR TKIs response prediction.
AB  - Epidermal growth factor receptor (EGFR) is a novel target for therapy in subsets
      of non-small cell lung cancer, especially adenocarcinoma. Tumors with EGFR
      mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We
      aimed to identify the discriminating capacity of immunohistochemical (IHC)
      scoring to detect L858R and E746-A750 deletion mutation in lung adenocarcinoma
      patients and predict EGFR TKIs response. Patients with surgically resected lung
      adenocarcinoma were enrolled. EGFR mutation status was genotyped by PCR and
      direct sequencing. Mutation-specific antibodies for L858R and E746-A750 deletion
      were used for IHC staining. Receiver operating characteristic (ROC) curves were
      used to determine the capacity of IHC, including intensity and/or quickscore (Q
      score), in differentiating L858R and E746-A750 deletion. We enrolled 143 patients
      during September 2000 to May 2009. Logistic-regression-model-based scoring
      containing both L858R Q score and total EGFR expression Q score was able to
      obtain a maximal area under the curve (AUC: 0.891) to differentiate the patients
      with L858R. Predictive model based on IHC Q score of E746-A750 deletion and IHC
      intensity of total EGFR expression reached an AUC of 0.969. The predictive model
      of L858R had a significantly higher AUC than L858R intensity only (p = 0.036). Of
      the six patients harboring complex EGFR mutations with classical mutation
      patterns, five had positive IHC staining. For EGFR TKI treated cancer recurrence
      patients, those with positive mutation-specific antibody IHC staining had better
      EGFR TKI response (p = 0.008) and longer progression-free survival (p = 0.012)
      than those without. In conclusion, total EGFR expression should be included in
      the IHC interpretation of L858R. After adjusting for total EGFR expression, the
      scoring method decreased the false positive rate and increased diagnostic power.
      According to the scoring method, the IHC method is useful to predict the clinical
      outcome and refine personalized therapy.

PMID- 21858065
TI  - Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and
      reparative neovascularization.
AB  - OBJECTIVE: Aging is associated with increased oxidative stress levels and
      impaired neovascularization following ischemia. CuZnSOD has an important role to
      limit oxidative stress in the vasculature. Here we investigated the role of
      CuZnSOD for the modulation of ischemia-induced neovascularisation during aging.
      METHODS AND RESULTS: Hindlimb ischemia was surgically induced in young (2- month
      old) or older (8-month-old) wild type (WT) and CuZnSOD(-/-) mice. We found that
      blood flow recovery after ischemia and vascular density in ischemic muscles were
      significantly reduced in older compared to young WT mice. Both in young and older
      mice, CuZnSOD deficiency led to a further reduction of neovascularization.
      Accordingly, the resulting neovascularisation potential in a young CuZnSOD(-/-)
      mouse was similar to that of an older WT mouse. Oxidative stress levels were also
      increased to similar levels in the ischemic muscles of young CuZnSOD(-/-) and
      older WT mice. To identify potential mechanisms involved, we investigated the
      effect of aging and CuZnSOD deficiency on the number and the function of
      endothelial progenitor cells (EPCs). Both aging and CuZnSOD deficiency were
      associated with reduced number of bone marrow and peripheral EPCs. The effect of
      moderate aging alone on specific functional activities of EPCs (migration,
      integration into tubules) was modest. However, CuZnSOD deficiency was associated
      with severe age-dependent defects in EPC functional activities. CONCLUSIONS:
      CuZnSOD deficiency is associated with accelerated vascular aging and impaired
      ischemia-induced neovascularization. Our results suggest that in the context of
      aging, CuZnSOD has an essential role to protect against excessive oxidative
      stress in ischemic tissues and preserve the function of EPCs.

PMID- 21858064
TI  - Magnesium limitation is an environmental trigger of the Pseudomonas aeruginosa
      biofilm lifestyle.
AB  - Biofilm formation is a conserved strategy for long-term bacterial survival in
      nature and during infections. Biofilms are multicellular aggregates of cells
      enmeshed in an extracellular matrix. The RetS, GacS and LadS sensors control the
      switch from a planktonic to a biofilm mode of growth in Pseudomonas aeruginosa.
      Here we detail our approach to identify environmental triggers of biofilm
      formation by investigating environmental conditions that repress expression of
      the biofilm repressor RetS. Mg(2+) limitation repressed the expression of retS
      leading to increased aggregation, exopolysaccharide (EPS) production and biofilm
      formation. Repression of retS expression under Mg(2+) limitation corresponded
      with induced expression of the GacA-controlled small regulatory RNAs rsmZ and
      rsmY and the EPS biosynthesis operons pel and psl. We recently demonstrated that
      extracellular DNA sequesters Mg(2+) cations and activates the cation-sensing
      PhoPQ two-component system, which leads to increased antimicrobial peptide
      resistance in biofilms. Here we show that exogenous DNA and EDTA, through their
      ability to chelate Mg(2+), promoted biofilm formation. The repression of retS in
      low Mg(2+) was directly controlled by PhoPQ. PhoP also directly controlled
      expression of rsmZ but not rsmY suggesting that PhoPQ controls the equilibrium of
      the small regulatory RNAs and thus fine-tunes the expression of genes in the RetS
      pathway. In summary, Mg(2+) limitation is a biologically relevant environmental
      condition and the first bonafide environmental signal identified that results in
      transcriptional repression of retS and promotes P. aeruginosa biofilm formation.

PMID- 21858066
TI  - A pan-HPV vaccine based on bacteriophage PP7 VLPs displaying broadly cross
      neutralizing epitopes from the HPV minor capsid protein, L2.
AB  - BACKGROUND: Current human papillomavirus (HPV) vaccines that are based on virus
      like particles (VLPs) of the major capsid protein L1 largely elicit HPV type
      specific antibody responses. In contrast, immunization with the HPV minor capsid
      protein L2 elicits antibodies that are broadly cross-neutralizing, suggesting
      that a vaccine targeting L2 could provide more comprehensive protection against
      infection by diverse HPV types. However, L2-based immunogens typically elicit
      much lower neutralizing antibody titers than L1 VLPs. We previously showed that a
      conserved broadly neutralizing epitope near the N-terminus of L2 is highly
      immunogenic when displayed on the surface of VLPs derived from the bacteriophage
      PP7. Here, we report the development of a panel of PP7 VLP-based vaccines
      targeting L2 that protect mice from infection with carcinogenic and non
      carcinogenic HPV types that infect the genital tract and skin.
      METHODOLOGY/PRINCIPAL FINDINGS: L2 peptides from eight different HPV types were
      displayed on the surface of PP7 bacteriophage VLPs. These recombinant L2 VLPs,
      both individually and in combination, elicited high-titer anti-L2 IgG serum
      antibodies. Immunized mice were protected from high dose infection with HPV
      pseudovirus (PsV) encapsidating a luciferase reporter. Mice immunized with 16L2
      PP7 VLPs or 18L2 PP7 VLPs were nearly completely protected from both PsV16 and
      PsV18 challenge. Mice immunized with the mixture of eight L2 VLPs were strongly
      protected from genital challenge with PsVs representing eight diverse HPV types
      and cutaneous challenge with HPV5 PsV. CONCLUSION/SIGNIFICANCE: VLP-display of a
      cross-neutralizing HPV L2 epitope is an effective approach for inducing high
      titer protective neutralizing antibodies and is capable of offering protection
      from a spectrum of HPVs associated with cervical cancer as well as genital and
      cutaneous warts.

PMID- 21858067
TI  - Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by
      photochemotherapy.
AB  - Photochemotherapy is used both for solid tumors and in extracorporeal treatment
      of various hematologic disorders. Nevertheless, its development in oncology
      remains limited, because of the low selectivity of photosensitizers (PS) towards
      human tumor cells. To enhance PS efficiency, we recently covalently linked a
      porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high
      affinity tumor-associated T and Tn antigens. The conjugation allowed a quick
      uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced
      phototoxicity. The present study was performed: (i) to evaluate the targeting
      potential of the conjugate towards tumor and normal cells and its phototoxicity
      on various leukemia cells, (ii) to investigate the mechanism of conjugate
      mediated cell death. The conjugate: (i) strongly increased (*1000) the PS
      phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent
      process; (ii) specifically purged tumor cells from a 1?1 mixture of Jurkat
      leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the
      activation potential of healthy lymphocytes; (iii) was effective against various
      leukemic cell lines with distinct phenotypes, as well as fresh human primary
      acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase
      independent cell death, which might be an advantage as tumor cells often resist
      caspase-dependent cell death. Altogether, the present observations suggest that
      conjugation with plant lectins can allow targeting of photosensitizers towards
      aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood
      and to preserve the normal leukocytes in extracorporeal photochemotherapy.

PMID- 21858069
TI  - Automatic prediction of facial trait judgments: appearance vs. structural models.
AB  - Evaluating other individuals with respect to personality characteristics plays a
      crucial role in human relations and it is the focus of attention for research in
      diverse fields such as psychology and interactive computer systems. In
      psychology, face perception has been recognized as a key component of this
      evaluation system. Multiple studies suggest that observers use face information
      to infer personality characteristics. Interactive computer systems are trying to
      take advantage of these findings and apply them to increase the natural aspect of
      interaction and to improve the performance of interactive computer systems. Here,
      we experimentally test whether the automatic prediction of facial trait judgments
      (e.g. dominance) can be made by using the full appearance information of the face
      and whether a reduced representation of its structure is sufficient. We evaluate
      two separate approaches: a holistic representation model using the facial
      appearance information and a structural model constructed from the relations
      among facial salient points. State of the art machine learning methods are
      applied to a) derive a facial trait judgment model from training data and b)
      predict a facial trait value for any face. Furthermore, we address the issue of
      whether there are specific structural relations among facial points that predict
      perception of facial traits. Experimental results over a set of labeled data (9
      different trait evaluations) and classification rules (4 rules) suggest that a)
      prediction of perception of facial traits is learnable by both holistic and
      structural approaches; b) the most reliable prediction of facial trait judgments
      is obtained by certain type of holistic descriptions of the face appearance; and
      c) for some traits such as attractiveness and extroversion, there are
      relationships between specific structural features and social perceptions.

PMID- 21858068
TI  - Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1)
      in hepatic cell proliferation at mononucleosomal resolution.
AB  - BACKGROUND: Gas1 (growth arrest-specific 1) gene is known to inhibit cell
      proliferation in a variety of models, but its possible implication in regulating
      quiescence in adult tissues has not been examined to date. The knowledge of how
      Gas1 is regulated in quiescence may contribute to understand the deregulation
      occurring in neoplastic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Gas1 expression
      has been studied in quiescent murine liver and during the naturally synchronized
      cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at
      nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving
      the in vivo conditions. Transcription has been assessed at real time by
      quantifying the presence of RNA polymerase II in coding regions (RNApol-ChIP). It
      has been found that Gas1 is expressed not only in quiescent liver but also at the
      cell cycle G(1)/S transition. The latter expression peak had not been previously
      reported. Two nucleosomes, flanking a nucleosome-free region, are positioned
      close to the transcription start site. Both nucleosomes slide in going from the
      active to the inactive state and vice versa. Nuc-ChIP analysis of the acquisition
      of histone epigenetic marks show distinctive features in both active states:
      H3K9ac and H3K4me2 are characteristic of transcription in G(0) and H4R3me2 in
      G(1)/S transition. Sequential-ChIP analysis revealed that the "repressing" mark
      H3K9me2 colocalize with several "activating" marks at nucleosome N-1 when Gas1 is
      actively transcribed suggesting a greater plasticity of epigenetic marks than
      proposed until now. The recruitment of chromatin-remodeling or modifying
      complexes also displayed distinct characteristics in quiescence and the G(1)/S
      transition. CONCLUSIONS/SIGNIFICANCE: The finding that Gas1 is transcribed at the
      G(1)/S transition suggests that the gene may exert a novel function during cell
      proliferation. Transcription of this gene is modulated by specific "activating"
      and "repressing" epigenetic marks, and by chromatin remodeling and histone
      modifying complexes recruitment, at specific nucleosomes in Gas1 promoter.

PMID- 21858070
TI  - Immunogenic properties of archaeal species found in bioaerosols.
AB  - The etiology of bioaerosol-related pulmonary diseases remains poorly understood.
      Recently, archaea emerged as prominent airborne components of agricultural
      environments, but the consequences of airway exposure to archaea remain unknown.
      Since subcomponents of archaea can be immunogenic, we used a murine model to
      study the pulmonary immune responses to two archaeal species found in
      agricultural facilities: Methanobrevibacter smithii (MBS) and Methanosphaera
      stadtmanae (MSS). Mice were administered intranasally with 6.25, 25 or 100 ug of
      MBS or MSS, once daily, 3 days a week, for 3 weeks. MSS induced more severe
      histopathological alterations than MBS with perivascular accumulation of
      granulocytes, pronounced thickening of the alveolar septa, alveolar macrophages
      accumulation and increased perivascular mononucleated cell accumulation. Analyses
      of bronchoalveolar lavage fluids revealed up to 3 times greater leukocyte
      accumulation with MSS compared to MBS. Instillation of 100 ug of MBS or MSS
      caused predominant accumulation of monocyte/macrophages (4.5*10(5) and 4.8*10(5)
      cells/ml respectively) followed by CD4(+) T cells (1.38*10(5) and 1.94*10(5)
      cells/ml respectively), B cells (0.73*10(5) and 1.28*10(5) cells/ml
      respectively), and CD8(+) T cells (0.20*10(5) and 0.31*10(5) cells/ml
      respectively) in the airways. Both archaeal species induced similar titers of
      antigen-specific IgGs in plasma. MSS but not MBS caused an accumulation of
      eosinophils and neutrophils in the lungs, which surprisingly, correlated
      inversely with the size of the inoculum. Stronger immunogenicity of MSS was
      confirmed by a 3 fold higher accumulation of myeloid dendritic cells in the
      airways, compared to MBS. Thus, the dose and species of archaea determine the
      magnitude and nature of the pulmonary immune response. This is the first report
      of an immunomodulatory role of archaeal species found in bioaerosols.

PMID- 21858071
TI  - The mitochondrial genome is a "genetic sanctuary" during the oncogenic process.
AB  - Since Otto Warburg linked mitochondrial physiology and oncogenesis in the 1930s,
      a number of studies have focused on the analysis of the genetic basis for the
      presence of aerobic glycolysis in cancer cells. However, little or no evidence
      exists today to indicate that mtDNA mutations are directly responsible for the
      initiation of tumor onset. Based on a model of gliomagenesis in the mouse, we
      aimed to explore whether or not mtDNA mutations are associated with the
      initiation of tumor formation, maintenance and aggressiveness. We reproduced the
      different molecular events that lead from tumor initiation to progression in the
      mouse glioma. In human gliomas, most of the genetic alterations that have been
      previously identified result in the aberrant activation of different signaling
      pathways and deregulation of the cell cycle. Our data indicates that
      mitochondrial dysfunction is associated with reactive oxygen species (ROS)
      generation, leading to increased nuclear DNA (nDNA) mutagenesis, but maintaining
      the integrity of the mitochondrial genome. In addition, mutational stability has
      been observed in entire mtDNA of human gliomas; this is in full agreement with
      the results obtained in the cancer mouse model. We use this model as a paradigm
      of oncogenic transformation due to the fact that mutations commonly found in
      gliomas appear to be the most common molecular alterations leading to tumor
      development in most types of human cancer. Our results indicate that the mtDNA
      genome is kept by the cell as a "genetic sanctuary" during tumor development in
      the mouse and humans. This is compatible with the hypothesis that the mtDNA
      molecule plays an essential role in the control of the cellular adaptive survival
      response to tumor-induced oxidative stress. The integrity of mtDNA seems to be a
      necessary element for responding to the increased ROS production associated with
      the oncogenic process.

PMID- 21858072
TI  - Long term follow-up of the endovascular trans-vessel wall technique for
      parenchymal access in rabbit with full clinical integration.
AB  - OBJECTIVE: Endovascular techniques are providing options to surgical/percutaneous
      cell transplantation methods. Some cells, e.g. insulin producing cells, are not
      suitable for intra-luminal transplantation and for such cells, other options must
      be found. We have constructed a "nanocatheter" with a penetrating tip for vessel
      perforation, thereby creating a working channel for parenchymal access by
      endovascular technique. To finish the procedure safely, the distal tip is
      detached to provide a securing plug in the vessel wall defect. MATERIALS AND
      METHODS: We have performed interventions with full clinical integration in the
      superior mesenteric artery (SMA), the subclavian artery and the external carotid
      artery in rabbits. No hemorrhagic- or thromboembolic events occurred during the
      procedure. Stenosis formation and distal embolisation were analyzed by
      angiography and macroscopic inspection during autopsy at five, 30 and 80 days.
      All animals and implanted devices were also evaluated by micro-dissections and
      histochemical analysis. RESULTS: In this study we show safety data on the trans
      vessel wall technique by behavioral, angiographical and histological analysis. No
      stenosis formation was observed at any of the follow-up time points. No animals
      or organs have shown any signs of distress due to the intervention. Histological
      examination showed no signs of hemorrhage, excellent biocompatibility with no
      inflammation and a very limited fibrous capsule formation around the device,
      comparable to titanium implants. Further, no histological changes were detected
      in the endothelia of the vessels subject to intervention. CONCLUSIONS: The trans
      vessel wall technique can be applied for e.g. cell transplantations, local
      substance administration and tissue sampling with low risk for complications
      during the procedure and low risk for hemorrhage, stenosis development or adverse
      tissue reactions with an 80 days follow-up time. The benefit should be greatest
      in organs that are difficult or risky to reach with surgical techniques, such as
      the pancreas, the CNS and the heart.

PMID- 21858073
TI  - An antibody to the lutheran glycoprotein (Lu) recognizing the LU4 blood type
      variant inhibits cell adhesion to laminin alpha5.
AB  - BACKGROUND: The Lutheran blood group glycoprotein (Lu), an Ig superfamily (IgSF)
      transmembrane receptor, is also known as basal cell adhesion molecule (B-CAM).
      Lu/B-CAM is a specific receptor for laminin alpha5, a major component of basement
      membranes in various tissues. Previous reports have shown that Lu/B-CAM binding
      to laminin alpha5 contributes to sickle cell vaso-occlusion. However, as there
      are no useful tools such as function-blocking antibodies or drugs, it is unclear
      how epithelial and sickled red blood cells adhere to laminin alpha5 via Lu/B-CAM.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we discovered a function-blocking
      antibody that inhibits Lu binding to laminin alpha5 using a unique binding assay
      on tissue sections. To characterize the function-blocking antibody, we identified
      the site on Lu/B-CAM recognized by this antibody. The extracellular domain of
      Lu/B-CAM contains five IgSF domains, D1-D2-D3-D4-D5. The antibody epitope was
      localized to D2, but not to the D3 domain containing the major part of the
      laminin alpha5 binding site. Furthermore, mutagenesis studies showed that
      Arg(175), the LU4 blood group antigenic site, was crucial for forming the epitope
      and the antibody bound sufficiently close to sterically hinder the interaction
      with alpha5. Cell adhesion assay using the antibody also showed that Lu/B-CAM
      serves as a secondary receptor for the adhesion of carcinoma cells to laminin
      alpha5. CONCLUSION/SIGNIFICANCE: This function-blocking antibody against Lu/B-CAM
      should be useful for not only investigating cell adhesion to laminin alpha5 but
      also for developing drugs to inhibit sickle cell vaso-occlusion.

PMID- 21858074
TI  - Invading basement membrane matrix is sufficient for MDA-MB-231 breast cancer
      cells to develop a stable in vivo metastatic phenotype.
AB  - INTRODUCTION: The poor efficacy of various anti-cancer treatments against
      metastatic cells has focused attention on the role of tumor microenvironment in
      cancer progression. To understand the contribution of the extracellular matrix
      (ECM) environment to this phenomenon, we isolated ECM surrogate invading cell
      populations from MDA-MB-231 breast cancer cells and studied their genotype and
      malignant phenotype. METHODS: We isolated invasive subpopulations (INV) from non
      invasive populations (REF) using a 2D-Matrigel assay, a surrogate of basal
      membrane passage. INV and REF populations were investigated by microarray assay
      and for their capacities to adhere, invade and transmigrate in vitro, and to form
      metastases in nude mice. RESULTS: REF and INV subpopulations were stable in
      culture and present different transcriptome profiles. INV cells were
      characterized by reduced expression of cell adhesion and cell-cell junction genes
      (44% of down regulated genes) and by a gain in expression of anti-apoptotic and
      pro-angiogenic gene sets. In line with this observation, in vitro INV cells
      showed reduced adhesion and increased motility through endothelial monolayers and
      fibronectin. When injected into the circulation, INV cells induced metastases
      formation, and reduced injected mice survival by up to 80% as compared to REF
      cells. In nude mice, INV xenografts grew rapidly inducing vessel formation and
      displaying resistance to apoptosis. CONCLUSION: Our findings reveal that the in
      vitro ECM microenvironment per se was sufficient to select for tumor cells with a
      stable metastatic phenotype in vivo characterized by loss of adhesion molecules
      expression and induction of pro-angiogenic and survival factors.

PMID- 21858075
TI  - Fix your eyes in the space you could reach: neurons in the macaque medial
      parietal cortex prefer gaze positions in peripersonal space.
AB  - Interacting in the peripersonal space requires coordinated arm and eye movements
      to visual targets in depth. In primates, the medial posterior parietal cortex
      (PPC) represents a crucial node in the process of visual-to-motor signal
      transformations. The medial PPC area V6A is a key region engaged in the control
      of these processes because it jointly processes visual information, eye position
      and arm movement related signals. However, to date, there is no evidence in the
      medial PPC of spatial encoding in three dimensions. Here, using single neuron
      recordings in behaving macaques, we studied the neural signals related to
      binocular eye position in a task that required the monkeys to perform saccades
      and fixate targets at different locations in peripersonal and extrapersonal
      space. A significant proportion of neurons were modulated by both gaze direction
      and depth, i.e., by the location of the foveated target in 3D space. The
      population activity of these neurons displayed a strong preference for
      peripersonal space in a time interval around the saccade that preceded fixation
      and during fixation as well. This preference for targets within reaching distance
      during both target capturing and fixation suggests that binocular eye position
      signals are implemented functionally in V6A to support its role in reaching and
      grasping.

PMID- 21858076
TI  - Adherence of pharmaceutical advertisements in medical journals to FDA guidelines
      and content for safe prescribing.
AB  - BACKGROUND: Physician-directed pharmaceutical advertising is regulated in the
      United States by the Food and Drug Administration (FDA); adherence to current FDA
      guidelines is unknown. Our objective was to determine adherence rates of
      physician-directed print advertisements in biomedical journals to FDA guidelines
      and describe content important for safe prescribing. METHODS AND FINDINGS: Cross
      sectional analysis of November 2008 pharmaceutical advertisements within top U.S.
      based biomedical journals publishing original research. We excluded
      advertisements for devices, over the counter medications, and disease awareness.
      We utilized FDA guideline items identifying unique forms of advertisement bias to
      categorize advertisements as adherent to FDA guidelines, possibly non-adherent to
      at least 1 item, or non-adherent to at least 1 item. We also evaluated
      advertisement content important for safe prescribing, including benefit
      quantification, risk information and verifiable references. All advertisements
      were evaluated by 2 or more investigators, with differences resolved by
      discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical
      advertisements, including 192 advertisements for 82 unique products; median 2 per
      product (range 1-14). Six "teaser" advertisements presented only drug names,
      leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to
      all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA
      described bias, and 27 (32.5%) were possibly non-adherent due to incomplete
      information. Content important for safe prescribing was often incomplete; 57.8%
      of advertisements did not quantify serious risks, 48.2% lacked verifiable
      references and 28.9% failed to present adequate efficacy quantification. Study
      limitations included its focus on advertisements from a single month, the
      subjectivity of FDA guidelines themselves, and the necessary subjectivity of
      determinations of adherence. CONCLUSIONS: Few physician-directed print
      pharmaceutical advertisements adhere to all FDA guidelines; over half fail to
      quantify serious risks. The FDA could better protect public health by creating
      new more objective advertisement guidelines requiring transparent presentation of
      basic safety and efficacy information.

PMID- 21858077
TI  - Confocal fluorescence anisotropy and FRAP imaging of alpha-synuclein amyloid
      aggregates in living cells.
AB  - We assessed the intracellular association states of the Parkinson's disease
      related protein alpha-synuclein (AS) in living cells by transfection with a
      functional recombinant mutant protein (AS-C4) bearing a tetracysteine tag binding
      the fluorogenic biarsenical ligands FlAsH and ReAsH, The aggregation states of AS
      C4 were assessed by in situ microscopy of molecular translational mobility with
      FRAP (fluorescence recovery after photobleaching) and of local molecular density
      with confocal fluorescence anisotropy (CFA). FRAP recovery was quantitative and
      rapid in regions of free protein, whereas AS in larger aggregates was>80%
      immobile. A small 16% recovery characterized by an apparent diffusion constant of
      0.03-0.04 um(2)/s was attributed to the dynamics of smaller, associated forms of
      AS-C4 and the exchange of mobile species with the larger immobile aggregates. By
      CFA, the larger aggregates exhibited high brightness and very low anisotropy,
      consistent with homoFRET between closely packed AS, for which a Forster distance
      (R(o)) of 5.3 nm was calculated. Other bright regions had high anisotropy values,
      close to that of monomeric AS, and indicative of membrane-associated protein with
      both low mobility and low degree of association. The anisotropy-fluorescence
      intensity correlations also revealed regions of free protein or of small
      aggregates, undetectable by conventional fluorescence imaging alone. The combined
      strategy (FRAP+CFA) provides a highly sensitive means for elucidating both the
      dynamics and structural features of protein aggregates and other intracellular
      complexes in living cells, and can be extended to other amyloid systems and to
      drug screening protocols.

PMID- 21858078
TI  - Molecular dynamics analysis reveals structural insights into mechanism of
      nicotine N-demethylation catalyzed by tobacco cytochrome P450 mono-oxygenase.
AB  - CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND)
      activity, which mediates the bioconversion of nicotine into nornicotine in
      senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco
      specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence
      identity, but it lacks NND activity. A recent site-directed mutagenesis study
      revealed that a single amino acid substitution, i.e., cysteine to tryptophan at
      the 330 position in the middle of protein, restores the NND activity of CYP82E3
      entirely. However, the same amino acid change caused the loss of the NND activity
      of CYP82E4. To determine the mechanism of the functional turnover of the two
      molecules, four 3D structures, i.e., the two molecules and their corresponding
      cys-trp mutants were modeled. The resulting structures exhibited that the
      mutation site is far from the active site, which suggests that no direct
      interaction occurs between the two sites. Simulation studies in different
      biological scenarios revealed that the mutation introduces a conformation drift
      with the largest change at the F-G loop. The dynamics trajectories analysis using
      principal component analysis and covariance analysis suggests that the single
      amino acid change causes the opening and closing of the transfer channels of the
      substrates, products, and water by altering the motion of the F-G and B-C loops.
      The motion of helix I is also correlated with the motion of both the F-G loop and
      the B-C loop and; the single amino acid mutation resulted in the curvature of
      helix I. These results suggest that the single amino acid mutation outside the
      active site region may have indirectly mediated the flexibility of the F-G and B
      C loops through helix I, causing a functional turnover of the P450 monooxygenase.

PMID- 21858079
TI  - Phylogeographic analyses reveal a crucial role of Xinjiang in HIV-1 CRF07_BC and
      HCV 3a transmissions in Asia.
AB  - BACKGROUND: China faces an increasing prevalence of two HIV-1 circulating
      recombinant forms (CRFs) 07_BC and 08_BC. Both CRFs_BC were previously
      demonstrated to originate in Yunnan and spread to Liaoning from Yunnan via
      injection drug use (IDU) in China. Supposing it is true, we are unable to answer
      why only CRF07_BC, rather than both CRFs_BC together, was transmitted to
      Xinjiang. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the phylogeography of
      CRF07_BC and CRF08_BC using multiple HIV-1 genomic regions with bayesian
      phylogeography method. Phylogenetic reconstructions showed that all CRF07_BC
      sequences were divided into two clades, Yunnan and Xinjiang, and all strains from
      other regions of mainland China clustered within the Xinjiang clade. Significant
      geographic diffusion links of Xinjiang with other regions (including Liaoning,
      Beijing, Jiangsu and Guangdong) were supported by Bayes factor tests. The
      temporal dynamics analyses showed that CRF07_BC spread from Xinjiang to Liaoning
      in 1996.10, and to Jiangsu in 2000.9. The analyses of CRF08_BC not only confirmed
      the previous conclusion on temporal and spatial dynamics of CRF08_BC, but also
      indicated that the CRF08_BC strains from Guangdong and Shanghai originated from
      Yunnan. The analyses of HCV 3a showed that it was introduced into Xinjiang in the
      early 1980s, and spread from Xinjiang to Yunnan in 1990.10 and to Jiangsu in
      1999.2, and further from Yunnan to Guangxi in 1995.3. The temporal and spatial
      dynamics of HCV 3a were similar to some extent to that of HIV-1 CRF07_BC and/or
      CRF08_BC, suggesting a possible association in migration patterns between HCV and
      HIV-1 through IDU. In addition, HCV 3a spread from Xinjiang to Pakistan, implying
      a drug trafficking route linking them. CONCLUSIONS/SIGNIFICANCE: Xinjiang, as the
      most important transfer station for drug trafficking from Golden Crescent to
      other regions of China, plays a very crucial role in the transmission of viruses
      (e.g., HIV-1 and HCV) through IDU in Asia.

PMID- 21858080
TI  - Interaction of hnRNPA1/A2 and DAZAP1 with an Alu-derived intronic splicing
      enhancer regulates ATM aberrant splicing.
AB  - We have previously identified an Alu-derived Intronic Splicing enhancer (ISE) in
      the Ataxia Teleangectasia Mutated gene (ATM) that facilitates intron pre-mRNA
      processing and leads to the inclusion of a cryptic exon in the final mRNA
      transcript. By using an RNA pull-down assay, we show here that hnRNPA1/A2, HuR
      and DAZAP1 splicing factors and DHX36 RNA helicase bind to the ISE. By functional
      studies (overexpression and siRNA experiments), we demonstrate that hnRNPA1 and
      DAZAP1 are indeed involved in ISE-dependent ATM cryptic exon activation, with
      hnRNPA1 acting negatively and DAZAP1 positively on splicing selection. On the
      contrary, HuR and DHX36 have no effect on ATM splicing pattern. These data
      suggest that splicing factors with both negative and positive effect can assemble
      on the intronic Alu repeats and regulate pre-mRNA splicing.

PMID- 21858081
TI  - The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated
      SEDT and TRAPPC9-associated congenital intellectual disability.
AB  - BACKGROUND: The TRAPP (Transport protein particle) complex is a conserved protein
      complex functioning at various steps in vesicle transport. Although yeast has
      three functionally and structurally distinct forms, TRAPPI, II and III, emerging
      evidence suggests that mammalian TRAPP complex may be different. Mutations in the
      TRAPP complex subunit 2 (TRAPPC2) cause X-linked spondyloepiphyseal dysplasia
      tarda, while mutations in the TRAPP complex subunit 9 (TRAPPC9) cause postnatal
      mental retardation with microcephaly. The structural interplay between these
      subunits found in mammalian equivalent of TRAPPI and those specific to TRAPPII
      and TRAPPIII remains largely unknown and we undertook the present study to
      examine the interaction between these subunits. Here, we reveal that the
      mammalian equivalent of the TRAPPII complex is structurally distinct from the
      yeast counterpart thus leading to insight into mechanism of disease. PRINCIPAL
      FINDINGS: We analyzed how TRAPPII- or TRAPPIII- specific subunits interact with
      the six-subunit core complex of TRAPP by co-immunoprecipitation in mammalian
      cells. TRAPPC2 binds to TRAPPII-specific subunit TRAPPC9, which in turn binds to
      TRAPPC10. Unexpectedly, TRAPPC2 can also bind to the putative TRAPPIII-specific
      subunit, TRAPPC8. Endogenous TRAPPC9-positive TRAPPII complex does not contain
      TRAPPC8, suggesting that TRAPPC2 binds to either TRAPPC9 or TRAPPC8 during the
      formation of the mammalian equivalents of TRAPPII or TRAPPIII, respectively.
      Therefore, TRAPPC2 serves as an adaptor for the formation of these complexes. A
      disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9
      or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of
      interaction with TRAPPC9 or TRAPPC8, mediating the formation of TRAPPII and/or
      TRAPPIII. Furthermore, disease-causing deletional mutants of TRAPPC9 all failed
      to interact with TRAPPC2 and TRAPPC10. CONCLUSIONS: TRAPPC2 serves as an adaptor
      for the formation of TRAPPII or TRAPPIII in mammalian cells. The mammalian
      equivalent of TRAPPII is likely different from the yeast TRAPPII structurally.

PMID- 21858082
TI  - A cytoplasmic negative regulator isoform of ATF7 impairs ATF7 and ATF2
      phosphorylation and transcriptional activity.
AB  - Alternative splicing and post-translational modifications are processes that give
      rise to the complexity of the proteome. The nuclear ATF7 and ATF2 (activating
      transcription factor) are structurally homologous leucine zipper transcription
      factors encoded by distinct genes. Stress and growth factors activate ATF2 and
      ATF7 mainly via sequential phosphorylation of two conserved threonine residues in
      their activation domain. Distinct protein kinases, among which mitogen-activated
      protein kinases (MAPK), phosphorylate ATF2 and ATF7 first on Thr71/Thr53 and next
      on Thr69/Thr51 residues respectively, resulting in transcriptional activation.
      Here, we identify and characterize a cytoplasmic alternatively spliced isoform of
      ATF7. This variant, named ATF7-4, inhibits both ATF2 and ATF7 transcriptional
      activities by impairing the first phosphorylation event on Thr71/Thr53 residues.
      ATF7-4 indeed sequesters the Thr53-phosphorylating kinase in the cytoplasm. Upon
      stimulus-induced phosphorylation, ATF7-4 is poly-ubiquitinated and degraded,
      enabling the release of the kinase and ATF7/ATF2 activation. Our data therefore
      conclusively establish that ATF7-4 is an important cytoplasmic negative regulator
      of ATF7 and ATF2 transcription factors.

PMID- 21858083
TI  - High diversity of the saliva microbiome in Batwa Pygmies.
AB  - We describe the saliva microbiome diversity in Batwa Pygmies, a former hunter
      gatherer group from Uganda, using next-generation sequencing of partial 16S rRNA
      sequences. Microbial community diversity in the Batwa is significantly higher
      than in agricultural groups from Sierra Leone and the Democratic Republic of
      Congo. We found 40 microbial genera in the Batwa, which have previously not been
      described in the human oral cavity. The distinctive composition of the salvia
      microbiome of the Batwa may have been influenced by their recent different
      lifestyle and diet.

PMID- 21858084
TI  - Caveolin-1-mediated apolipoprotein A-I membrane binding sites are not required
      for cholesterol efflux.
AB  - Caveolin-1 (Cav1), a structural protein required for the formation of invaginated
      membrane domains known as caveolae, has been implicated in cholesterol
      trafficking and homeostasis. Here we investigated the contribution of Cav1 to
      apolipoprotein A-I (apoA-I) cell surface binding and intracellular processing
      using mouse embryonic fibroblasts (MEFs) derived from wild type (WT) or Cav1
      deficient (Cav1(-/-)) animals. We found that cells expressing Cav1 have 2.6-fold
      more apoA-I binding sites than Cav1(-/-) cells although these additional binding
      sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated
      binding targets apoA-I for internalization and degradation and these processes
      are not correlated to cholesterol efflux. Despite lower apoA-I binding,
      cholesterol efflux from Cav1(-/-) MEFs is 1.7-fold higher than from WT MEFs.
      Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux
      from both WT and Cav1(-/-) cells without increasing apoA-I surface binding or
      affecting apoA-I processing. Our results indicate that there are at least two
      independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding
      and uptake is not linked to cholesterol efflux, indicating that membrane domains
      other than caveolae regulate ABCA1-mediated cholesterol efflux.

PMID- 21858085
TI  - The initiation of GTP hydrolysis by the G-domain of FeoB: insights from a
      transition-state complex structure.
AB  - The polytopic membrane protein FeoB is a ferrous iron transporter in prokaryotes.
      The protein contains a potassium-activated GTPase domain that is essential in
      regulating the import of iron and conferring virulence to many disease-causing
      bacteria. However, the mechanism by which the G-domain of FeoB hydrolyzes GTP is
      not well understood. In particular, it is not yet known how the pivotal step in
      GTP hydrolysis is achieved: alignment of a catalytic water molecule. In the
      current study, the crystal structure of the soluble domains from Streptococcus
      thermophilus FeoB (NFeoB(St)) in complex with the activating potassium ion and a
      transition-state analogue, GDP?AlF(4) (-), reveals a novel mode of water
      alignment involving contacts with the protein backbone only. In parallel to the
      structural studies, a series of seven mutant proteins were constructed that
      targeted conserved residues at the active site of NFeoB(St), and the nucleotide
      binding and hydrolysis properties of these were measured and compared to the wild
      type protein. The results show that mutations in Thr35 abolish GTPase activity of
      the protein, while other conserved residues (Tyr58, Ser64, Glu66 and Glu67) are
      not required for water alignment by NFeoB(St). Together with the crystal
      structure, the findings suggest a new mechanism for hydrolysis initiation in
      small G-proteins, in which the attacking water molecule is aligned by contacts
      with the protein backbone only.

PMID- 21858086
TI  - GEP100-Arf6-AMAP1-cortactin pathway frequently used in cancer invasion is
      activated by VEGFR2 to promote angiogenesis.
AB  - Angiogenesis and cancer invasiveness greatly contribute to cancer malignancy.Arf6
      and its effector, AMAP1, are frequently overexpressed in breast cancer, and
      constitute a central pathway to induce the invasion and metastasis. In this
      pathway, Arf6 is activated by EGFR via GEP100. Arf6 is highly expressed also in
      human umbilical vein endothelial cells (HUVECs) and is implicated in
      angiogenesis. Here, we found that HUVECs also highly express AMAP1, and that
      vascular endothelial growth factor receptor-2 (VEGFR2) recruits GEP100 to
      activate Arf6. AMAP1 functions by binding to cortactin in cancer invasion and
      metastasis. We demonstrate that the same GEP100-Arf6-AMAP1-cortactin pathway is
      essential for angiogenesis activities, including cell migration and tubular
      formation, as well as for the enhancement of cell permeability and VE-cadherin
      endocytosis of VEGF-stimulated HUVECs. Components of this pathway are highly
      expressed in pathologic angiogenesis, and blocking of this pathway effectively
      inhibits VEGF- or tumor-induced angiogenesis and choroidal neovascularization.
      The GEP100-Arf6-AMAP1-cortactin pathway, activated by receptor tyrosine kinases,
      appears to be common in angiogenesis and cancer invasion and metastasis, and
      provides their new therapeutic targets.

PMID- 21858087
TI  - A booster vaccine expressing a latency-associated antigen augments BCG induced
      immunity and confers enhanced protection against tuberculosis.
AB  - BACKGROUND: In spite of a consistent protection against tuberculosis (TB) in
      children, Mycobacterium bovis Bacille Calmette-Guerin (BCG) fails to provide
      adequate protection against the disease in adults as well as against reactivation
      of latent infections or exogenous reinfections. It has been speculated that
      failure to generate adequate memory T cell response, elicitation of inadequate
      immune response against latency-associated antigens and inability to impart long
      term immunity against M. tuberculosis infections are some of the key factors
      responsible for the limited efficiency of BCG in controlling TB.
      METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA
      vaccine expressing alpha-crystallin--a key latency antigen of M. tuberculosis to
      boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D) confers
      robust protection in guinea pigs along with a reduced pathology in comparison to
      BCG vaccination (1.37 log(10) and 1.96 log(10) fewer bacilli in lungs and spleen,
      respectively; p<0.01). In addition, B/D regimen also confers enhanced protection
      in mice. Further, we show that B/D immunization in mice results in a heightened
      frequency of PPD and antigen specific multi-functional CD4 T cells (3(+))
      simultaneously producing interferon (IFN)gamma, tumor necrosis factor (TNF)alpha
      and interleukin (IL)2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate
      the superiority of alpha-crystallin based B/D regimen over BCG. Our study, also
      demonstrates that protection against TB is predictable by an increased frequency
      of 3(+) Th1 cells with superior effector functions. We anticipate that this study
      would significantly contribute towards the development of superior booster
      vaccines for BCG vaccinated individuals. In addition, this regimen can also be
      expected to reduce the risk of developing active TB due to reactivation of latent
      infection.

PMID- 21858088
TI  - Oxytocin and vasopressin involved in restraint water-immersion stress mediated by
      oxytocin receptor and vasopressin 1b receptor in rat brain.
AB  - AIMS: Vasopressin (AVP) and oxytocin (OT) are considered to be related to gastric
      functions and the regulation of stress response. The present study was to study
      the role of vasopressinergic and oxytocinergic neurons during the restraint water
      immersion stress. METHODS: Ten male Wistar rats were divided into two groups,
      control and RWIS for 1h. The brain sections were treated with a dual
      immunohistochemistry of Fos and oxytocin (OT) or vasopressin (AVP) or OT receptor
      or AVP 1b receptor (V(1b)R). RESULTS: (1) Fos-immunoreactive (Fos-IR) neurons
      dramatically increased in the hypothalamic paraventricular nucleus (PVN), the
      supraoptic nucleus (SON), the nucleus of solitary tract (NTS) and motor nucleus
      of the vagus (DMV) in the RWIS rats; (2) OT-immunoreactive (OT-IR) neurons were
      mainly observed in the medial magnocellular part of the PVN and the dorsal
      portion of the SON, while AVP-immunoreactive (AVP-IR) neurons mainly distributed
      in the magnocellular part of the PVN and the ventral portion of the SON. In the
      RWIS rats, Fos-IR neurons were identified in 31% of OT-IR neurons and 40% of AVP
      IR neurons in the PVN, while in the SON it represented 28%, 53% respectively; (3)
      V(1b)R-IR and OTR-IR neurons occupied all portions of the NTS and DMV. In the
      RWIS rats, more than 10% of OTR-IR and V(1b)R-IR neurons were activated in the
      DMV, while lower ratio in the NTS. CONCLUSION: RWIS activates both oxytocinergic
      and vasopressinergic neurons in the PVN and SON, which may project to the NTS or
      DMV mediating the activity of the neurons by OTR and V(1b)R.

PMID- 21858089
TI  - Autophagy impairment induces premature senescence in primary human fibroblasts.
AB  - BACKGROUND: Recent studies have demonstrated that activation of autophagy
      increases the lifespan of organisms from yeast to flies. In contrast to the
      lifespan extension effect in lower organisms, it has been reported that
      overexpression of unc-51-like kinase 3 (ULK3), the mammalian homolog of autophagy
      specific gene 1 (ATG1), induces premature senescence in human fibroblasts.
      Therefore, we assessed whether the activation of autophagy would genuinely induce
      premature senescence in human cells. METHODOLOGY/PRINCIPAL FINDINGS: Depletion of
      ATG7, ATG12, or lysosomal-associated membrane protein 2 (Lamp2) by transfecting
      siRNA or infecting cells with a virus containing gene-specific shRNA resulted in
      a senescence-like state in two strains of primary human fibroblasts. Prematurely
      senescent cells induced by autophagy impairment exhibited the senescent
      phenotypes, similar to the replicatively senescent cells, such as increased
      senescence associated beta-galactosidase (SA-beta-gal) activity, reactive oxygen
      species (ROS) generation, and accumulation of lipofuscin. In addition, expression
      levels of ribosomal protein S6 kinase1 (S6K1), p-S6K1, p-S6, and eukaryotic
      translation initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) in the
      mammalian target of rapamycin (mTOR) pathway and beclin-1, ATG7, ATG12-ATG5
      conjugate, and the sequestosome 1 (SQSTM1/p62) monomer in the autophagy pathway
      were decreased in both the replicatively and the autophagy impairment-induced
      prematurely senescent cells. Furthermore, it was found that ROS scavenging by N
      acetylcysteine (NAC) and inhibition of p53 activation by pifithrin-alpha or
      knockdown of p53 using siRNA, respectively, delayed autophagy impairment-induced
      premature senescence and restored the expression levels of components in the mTOR
      and autophagy pathways. CONCLUSION: Taken together, we concluded that autophagy
      impairment induces premature senescence through a ROS- and p53-dependent manner
      in primary human fibroblasts.

PMID- 21858090
TI  - Mechanisms of resistance to decitabine in the myelodysplastic syndrome.
AB  - PURPOSE: The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC) is approved
      for the treatment of myelodysplastic syndromes (MDS), but resistance to DAC
      develops during treatment and mechanisms of resistance remain unknown. Therefore,
      we investigated mechanisms of primary and secondary resistance to DAC in MDS.
      PATIENTS AND METHODS: We performed Quantitative Real-Time PCR to examine
      expression of genes related to DAC metabolism prior to therapy in 32 responders
      and non-responders with MDS as well as 14 patients who achieved a complete
      remission and subsequently relapsed while on therapy (secondary resistance). We
      then performed quantitative methylation analyses by bisulfite pyrosequencing of
      10 genes as well as Methylated CpG Island Amplification Microarray (MCAM)
      analysis of global methylation in secondary resistance. RESULTS: Most genes
      showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non
      responders than responders (P<.05), suggesting that this could be a mechanism of
      primary resistance. There were no significant differences at relapse in DAC
      metabolism genes, and no DCK mutations were detected. Global methylation measured
      by the LINE1 assay was lower at relapse than at diagnosis (P<.05). On average,
      the methylation of 10 genes was lower at relapse (16.1%) compared to diagnosis
      (18.1%) (P<.05). MCAM analysis showed decreased methylation of an average of 4.5%
      (range 0.6%-9.7%) of the genes at relapse. By contrast, new cytogenetic changes
      were found in 20% of patients. CONCLUSION: Pharmacological mechanisms are
      involved in primary resistance to DAC, whereas hypomethylation does not prevent a
      relapse for patients with DAC treatment.

PMID- 21858091
TI  - In vitro and ex vivo analysis of CHRNA3 and CHRNA5 haplotype expression.
AB  - Genome-wide association studies implicate variations in CHRNA5 and CHRNA3 as
      being associated with nicotine addiction (NA). Multiple common haplotypes
      ("risk", "mixed" and "protective") exist in Europeans; however, high linkage
      disequilibrium between variations in CHRNA5 and CHRNA3 makes assigning causative
      allele(s) for NA difficult through genotyping experiments alone. We investigated
      whether CHRNA5 or CHRNA3 promoter haplotypes, associated previously with NA,
      might influence allelic expression levels. For in vitro analyses, promoter
      haplotypes were sub-cloned into a luciferase reporter vector. When assessed in
      BE(2)-C cells, luciferase expression was equivalent among CHRNA3 haplotypes, but
      the combination of deletion at rs3841324 and variation at rs503464 decreased
      CHRNA5 promoter-derived luciferase activity, possibly due to loss of an SP-1 and
      other site(s). Variation within the CHRNA5 5'UTR at rs55853698 and rs55781567
      also altered luciferase expression in BE(2)-C cells. Allelic expression imbalance
      (AEI) from the "risk" or "protective" haplotypes was assessed in post-mortem
      brain tissue from individuals heterozygous at coding polymorphisms in CHRNA3
      (rs1051730) or CHRNA5 (rs16969968). In most cases, equivalent allelic expression
      was observed; however, one individual showed CHRNA5 AEI that favored the
      "protective" allele and that was concordant with heterozygosity at polymorphisms
      ~13.5 kb upstream of the CHRNA5 transcription start site. Putative enhancer
      activity from these distal promoter elements was assessed using heterologous
      promoter constructs. We observed no differences in promoter activity from the two
      distal promoter haplotypes examined, but found that the distal promoter region
      strongly repressed transcription. We conclude that CHRNA5 promoter variants may
      affect relative risk for NA in some heterozygous individuals.

PMID- 21858093
TI  - Duality between time series and networks.
AB  - Studying the interaction between a system's components and the temporal evolution
      of the system are two common ways to uncover and characterize its internal
      workings. Recently, several maps from a time series to a network have been
      proposed with the intent of using network metrics to characterize time series.
      Although these maps demonstrate that different time series result in networks
      with distinct topological properties, it remains unclear how these topological
      properties relate to the original time series. Here, we propose a map from a time
      series to a network with an approximate inverse operation, making it possible to
      use network statistics to characterize time series and time series statistics to
      characterize networks. As a proof of concept, we generate an ensemble of time
      series ranging from periodic to random and confirm that application of the
      proposed map retains much of the information encoded in the original time series
      (or networks) after application of the map (or its inverse). Our results suggest
      that network analysis can be used to distinguish different dynamic regimes in
      time series and, perhaps more importantly, time series analysis can provide a
      powerful set of tools that augment the traditional network analysis toolkit to
      quantify networks in new and useful ways.

PMID- 21858092
TI  - Premature osteoblast clustering by enamel matrix proteins induces osteoblast
      differentiation through up-regulation of connexin 43 and N-cadherin.
AB  - In recent years, enamel matrix derivative (EMD) has garnered much interest in the
      dental field for its apparent bioactivity that stimulates regeneration of
      periodontal tissues including periodontal ligament, cementum and alveolar bone.
      Despite its widespread use, the underlying cellular mechanisms remain unclear and
      an understanding of its biological interactions could identify new strategies for
      tissue engineering. Previous in vitro research has demonstrated that EMD promotes
      premature osteoblast clustering at early time points. The aim of the present
      study was to evaluate the influence of cell clustering on vital osteoblast cell
      cell communication and adhesion molecules, connexin 43 (cx43) and N-cadherin (N
      cad) as assessed by immunofluorescence imaging, real-time PCR and Western blot
      analysis. In addition, differentiation markers of osteoblasts were quantified
      using alkaline phosphatase, osteocalcin and von Kossa staining. EMD significantly
      increased the expression of connexin 43 and N-cadherin at early time points
      ranging from 2 to 5 days. Protein expression was localized to cell membranes when
      compared to control groups. Alkaline phosphatase activity was also significantly
      increased on EMD-coated samples at 3, 5 and 7 days post seeding. Interestingly,
      higher activity was localized to cell cluster regions. There was a 3 fold
      increase in osteocalcin and bone sialoprotein mRNA levels for osteoblasts
      cultured on EMD-coated culture dishes. Moreover, EMD significantly increased
      extracellular mineral deposition in cell clusters as assessed through von Kossa
      staining at 5, 7, 10 and 14 days post seeding. We conclude that EMD up-regulates
      the expression of vital osteoblast cell-cell communication and adhesion
      molecules, which enhances the differentiation and mineralization activity of
      osteoblasts. These findings provide further support for the clinical evidence
      that EMD increases the speed and quality of new bone formation in vivo.

PMID- 21858094
TI  - Food composition of the diet in relation to changes in waist circumference
      adjusted for body mass index.
AB  - BACKGROUND: Dietary factors such as low energy density and low glycemic index
      were associated with a lower gain in abdominal adiposity. A better understanding
      of which food groups/items contribute to these associations is necessary.
      OBJECTIVE: To ascertain the association of food groups/items consumption on
      prospective annual changes in "waist circumference for a given BMI" (WC(BMI)), a
      proxy for abdominal adiposity. DESIGN: We analyzed data from 48,631 men and women
      from 5 countries participating in the European Prospective Investigation into
      Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at
      baseline and after a median follow-up time of 5.5 years. WC(BMI) was defined as
      the residuals of waist circumference regressed on BMI, and annual change in
      WC(BMI) (DeltaWC(BMI), cm/y) was defined as the difference between residuals at
      follow-up and baseline, divided by follow-up time. The association between food
      groups/items and DeltaWC(BMI) was modelled using centre-specific adjusted linear
      regression, and random-effects meta-analyses to obtain pooled estimates. RESULTS:
      Higher fruit and dairy products consumption was associated with a lower gain in
      WC(BMI) whereas the consumption of white bread, processed meat, margarine, and
      soft drinks was positively associated with DeltaWC(BMI). When these six food
      groups/items were analyzed in combination using a summary score, those in the
      highest quartile of the score--indicating a more favourable dietary pattern-
      showed a DeltaWC(BMI) of -0.11 (95% CI -0.09 to -0.14) cm/y compared to those in
      the lowest quartile. CONCLUSION: A dietary pattern high in fruit and dairy and
      low in white bread, processed meat, margarine, and soft drinks may help to
      prevent abdominal fat accumulation.

PMID- 21858095
TI  - Nuclear pore complex protein mediated nuclear localization of dicer protein in
      human cells.
AB  - Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step
      in production of single-stranded RNAs which are mediating factors of cytoplasmic
      RNA interference. Here, we clearly demonstrate that human DICER1 protein
      localizes not only to the cytoplasm but also to the nucleoplasm. We also find
      that human DICER1 protein associates with the NUP153 protein, one component of
      the nuclear pore complex. This association is detected predominantly in the
      cytoplasm but is also clearly distinguishable at the nuclear periphery.
      Additional characterization of the NUP153-DICER1 association suggests NUP153
      plays a crucial role in the nuclear localization of the DICER1 protein.

PMID- 21858096
TI  - Malaria morbidity in children in the year after they had received intermittent
      preventive treatment of malaria in Mali: a randomized control trial.
AB  - BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) is a
      promising strategy for malaria control. A study conducted in Mali in 2008 showed
      that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP)
      and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe
      malaria and malaria infection by >80% in children under 5 years of age. Here we
      report the results of a follow-on study undertaken to establish whether children
      who had received IPTc would be at increased risk of malaria during the subsequent
      malaria transmission season. METHODS: Morbidity from malaria and the prevalence
      of malaria parasitaemia and anaemia were measured in children who had previously
      received IPTc with SP and AQ using similar surveillance methods to those employed
      during the previous intervention period. RESULTS: 1396 of 1508 children (93%) who
      had previously received IPTc and 1406 of 1508 children (93%) who had previously
      received placebos were followed up during the high malaria transmission season of
      the year following the intervention. Incidence rates of clinical malaria during
      the post-intervention transmission season (July-November 2009) were 1.87 (95% CI
      1.76-1.99) and 1.73 (95% CI; 1.62-1.85) episodes per child year in the previous
      intervention and placebo groups respectively; incidence rate ratio (IRR) 1.09
      (95% CI 0.99-1.21) (P = 0.08). The prevalence of malaria infection was similar in
      the two groups, 7.4% versus 7.5%, prevalence ratio (PR) of 0.99 (95% CI 0.73
      1.33) (P = 0.95). At the end of post-intervention malaria transmission season,
      the prevalence of anaemia, defined as a haemoglobin concentration<11g/dL, was
      similar in the two groups (56.2% versus 55.6%; PR = 1.01 [95% CI 0.91-1.12]) (P =
      0.84). CONCLUSION: IPTc with SP+AQ was not associated with an increase in
      incidence of malaria episodes, prevalence of malaria infection or anaemia in the
      subsequent malaria transmission season. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00738946.

PMID- 21858097
TI  - Morbidity from malaria in children in the year after they had received
      intermittent preventive treatment of malaria: a randomised trial.
AB  - BACKGROUND: Interventions that reduce exposure to malaria infection may lead to
      delayed malaria morbidity and mortality. We investigated whether intermittent
      preventive treatment of malaria in children (IPTc) was associated with an
      increase in the incidence of malaria after cessation of the intervention.
      METHODS: An individually randomised, trial of IPTc, comparing three courses of
      sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was
      implemented in children aged 3-59 months during the 2008 malaria transmission
      season in Burkina Faso. All children in the trial were given a long lasting
      insecticide treated net; 1509 children received SP+AQ and 1505 received placebos.
      Passive surveillance for malaria was maintained until the end of the subsequent
      malaria transmission season in 2009, and active surveillance for malaria
      infection, anaemia and malnutrition was conducted. RESULTS: On thousand, four
      hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled
      in the intervention and control arms of the trial respectively were followed
      during the 2009 malaria transmission season. During the period July 2009 to
      November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67-4.02)
      and 3.45 (95%CI; 3.29-3.62) episodes per child during the follow up period in
      children who had previously received IPT or placebos, indicating a small increase
      in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04-1.20)
      (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria
      infection (adjusted PR: 0.88 95%CI: 0.79-0.98) (P = 0.04) but they had a higher
      parasite density (P = 0.001) if they were infected. There was no evidence that
      the risks of moderately severe anaemia (Hb<8 g/dL), wasting, stunting, or of
      being underweight in children differed between treatment arms. CONCLUSION: IPT
      with SP+AQ was associated with a small increase in the incidence of clinical
      malaria in the subsequent malaria transmission season. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00738946.

PMID- 21858098
TI  - Effects of clinically relevant MPL mutations in the transmembrane domain revealed
      at the atomic level through computational modeling.
AB  - BACKGROUND: Mutations in the thrombopoietin receptor (MPL) may activate relevant
      pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms
      of MPL activation remain elusive because of a lack of experimental structures.
      Modern computational biology techniques were utilized to explore the mechanisms
      of MPL protein activation due to various mutations. RESULTS: Transmembrane (TM)
      domain predictions, homology modeling, ab initio protein structure prediction,
      and molecular dynamics (MD) simulations were used to build structural dynamic
      models of wild-type and four clinically observed mutants of MPL. The simulation
      results suggest that S505 and W515 are important in keeping the TM domain in its
      correct position within the membrane. Mutations at either of these two positions
      cause movement of the TM domain, altering the conformation of the nearby
      intracellular domain in unexpected ways, and may cause the unwanted constitutive
      activation of MPL's kinase partner, JAK2. CONCLUSIONS: Our findings represent the
      first full-scale molecular dynamics simulations of the wild-type and clinically
      observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT
      signaling pathway. In contrast to usual explanations for the activation mechanism
      that are based on the relative translational movement between rigid domains of
      MPL, our results suggest that mutations within the TM region could result in
      conformational changes including tilt and rotation (azimuthal) angles along the
      membrane axis. Such changes may significantly alter the conformation of the
      adjacent and intrinsically flexible intracellular domain. Hence, caution should
      be exercised when interpreting experimental evidence based on rigid models of
      cytokine receptors or similar systems.

PMID- 21858099
TI  - Persistence of environmental DNA in freshwater ecosystems.
AB  - The precise knowledge of species distribution is a key step in conservation
      biology. However, species detection can be extremely difficult in many
      environments, specific life stages and in populations at very low density. The
      aim of this study was to improve the knowledge on DNA persistence in water in
      order to confirm the presence of the focus species in freshwater ecosystems.
      Aquatic vertebrates (fish: Siberian sturgeon and amphibian: Bullfrog tadpoles)
      were used as target species. In control conditions (tanks) and in the field
      (ponds), the DNA detectability decreases with time after the removal of the
      species source of DNA. DNA was detectable for less than one month in both
      conditions. The density of individuals also influences the dynamics of DNA
      detectability in water samples. The dynamics of detectability reflects the
      persistence of DNA fragments in freshwater ecosystems. The short time persistence
      of detectable amounts of DNA opens perspectives in conservation biology, by
      allowing access to the presence or absence of species e.g. rare, secretive,
      potentially invasive, or at low density. This knowledge of DNA persistence will
      greatly influence planning of biodiversity inventories and biosecurity surveys.

PMID- 21858100
TI  - Plasma L-cystine/L-glutamate imbalance increases tumor necrosis factor-alpha from
      CD14+ circulating monocytes in patients with advanced cirrhosis.
AB  - BACKGROUND AND AIMS: The innate immune cells can not normally respond to the
      pathogen in patients with decompensated cirrhosis. Previous studies reported that
      antigen-presenting cells take up L-Cystine (L-Cys) and secrete substantial
      amounts of L-Glutamate (L-Glu) via the transport system Xc- (4F2hc+xCT), and that
      this exchange influences the immune responses. The aim of this study is to
      investigate the influence of the plasma L-Cys/L-Glu imbalance observed in
      patients with advanced cirrhosis on the function of circulating monocytes.
      METHODS: We used a serum-free culture medium consistent with the average
      concentrations of plasma amino acids from patients with advanced cirrhosis (ACM),
      and examined the function of CD14+ monocytes or THP-1 under ACM that contained 0
      300 nmol/mL L-Cys with LPS. In patients with advanced cirrhosis, we actually
      determined the TNF-alpha and xCT mRNA of monocytes, and evaluated the correlation
      between the plasma L-Cys/L-Glu ratio and TNF-alpha. RESULTS: The addition of L
      Cys significantly increased the production of TNF alpha from monocytes under ACM.
      Monocytes with LPS and THP-1 expressed xCT and a high level of extracellular L
      Cys enhanced L-Cys/L-Glu antiport, and the intracellular GSH/GSSG ratio was
      decreased. The L-Cys transport was inhibited by excess L-Glu. In patients with
      advanced cirrhosis (n = 19), the TNF-alpha and xCT mRNA of monocytes were
      increased according to the Child-Pugh grade. The TNF-alpha mRNA of monocytes was
      significantly higher in the high L-Cys/L-Glu ratio group than in the low ratio
      group, and the plasma TNF-alpha was significantly correlated with the L-Cys/L-Glu
      ratio. CONCLUSIONS: A plasma L-Cys/L-Glu imbalance, which appears in patients
      with advanced cirrhosis, increased the TNF-alpha from circulating monocytes via
      increasing the intracellular oxidative stress. These results may reflect the
      immune abnormality that appears in patients with decompensated cirrhosis.

PMID- 21858101
TI  - Multiple Cytochrome P450 genes: their constitutive overexpression and permethrin
      induction in insecticide resistant mosquitoes, Culex quinquefasciatus.
AB  - Four cytochrome P450 cDNAs, CYP6AA7, CYP9J40, CYP9J34, and CYP9M10, were isolated
      from mosquitoes, Culex quinquefasciatus. The P450 gene expression and induction
      by permethrin were compared for three different mosquito populations bearing
      different resistance phenotypes, ranging from susceptible (S-Lab), through
      intermediate (HAmCq(G0), the field parental population) to highly resistant
      (HAmCq(G8), the 8(th) generation of permethrin selected offspring of HAmCq(G0)).
      A strong correlation was found for P450 gene expression with the levels of
      resistance and following permethrin selection at the larval stage of mosquitoes,
      with the highest expression levels identified in HAmCq(G8), suggesting the
      importance of CYP6AA7, CYP9J40, CYP9J34, and CYP9M10 in the permethrin resistance
      of larva mosquitoes. Only CYP6AA7 showed a significant overexpression in
      HAmCq(G8) adult mosquitoes. Other P450 genes had similar expression levels among
      the mosquito populations tested, suggesting different P450 genes may be involved
      in the response to insecticide pressure in different developmental stages. The
      expression of CYP6AA7, CYP9J34, and CYP9M10 was further induced by permethrin in
      resistant mosquitoes. Taken together, these results indicate that multiple P450
      genes are up-regulated in insecticide resistant mosquitoes through both
      constitutive overexpression and induction mechanisms, thus increasing the overall
      expression levels of P450 genes.

PMID- 21858102
TI  - Degenerate wave and capacitive coupling increase human MSC invasion and
      proliferation while reducing cytotoxicity in an in vitro wound healing model.
AB  - Non-unions pose complications in fracture management that can be treated using
      electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are
      essential in fracture healing; however, the effect of different clinical ES
      waveforms on BMMSCs cellular activities remains unknown. We compared the effects
      of direct current (DC), capacitive coupling (CC), pulsed electromagnetic field
      (PEMF) and degenerate wave (DW) on cellular activities including cytotoxicity,
      proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a
      day, up to 5 days. In addition, migration and invasion were assessed using
      fluorescence microscopy and by quantifying gene and protein expression. We found
      that DW had the greatest proliferative and least apoptotic and cytotoxic effects
      compared to other waveforms. DC, DW and CC stimulations resulted in a higher
      number of cells in S phase and G(2)/M phase as shown by cell cycle analysis. CC
      and DW caused more cells to invade collagen and showed increased MMP-2 and MT1
      MMP expression. DC increased cellular migration in a scratch-wound assay and all
      ES waveforms enhanced expression of migratory genes with DC having the greatest
      effect. All ES treated cells showed similar progenitor potential as determined by
      MSC differentiation assay. All above findings were shown to be statistically
      significant (p<0.05). We conclude that ES can influence BMMSCs activities,
      especially DW and CC, which show greater invasion and higher cell proliferation
      compared to other types of ES. Application of DW or CC to the fracture site may
      help in the recruitment of BMMSCs to the wound that may enhance rate of bone
      healing at the fracture site.

PMID- 21858103
TI  - Unique changes in mitochondrial genomes associated with reversions of S-type
      cytoplasmic male sterility in maizemar.
AB  - Cytoplasmic male sterility (CMS) in plants is usually associated with the
      expression of specific chimeric regions within rearranged mitochondrial genomes.
      Maize CMS-S plants express high amounts of a 1.6-kb mitochondrial RNA during
      microspore maturation, which is associated with the observed pollen abortion.
      This transcript carries two chimeric open reading frames, orf355 and orf77, both
      unique to CMS-S. CMS-S mitochondria also contain free linear DNA plasmids bearing
      terminal inverted repeats (TIRs). These TIRs recombine with TIR-homologous
      sequences that precede orf355/orf77 within the main mitochondrial genome to
      produce linear ends. Transcription of the 1.6-kb RNA is initiated from a promoter
      within the TIRs only when they are at linear ends. Reversions of CMS-S to
      fertility occur in certain nuclear backgrounds and are usually associated with
      loss of the S plasmids and/or the sterility-associated region. We describe an
      unusual set of independently recovered revertants from a single maternal lineage
      that retain both the S plasmids and an intact orf355/orf77 region but which do
      not produce the 1.6-kb RNA. A 7.3-kb inversion resulting from illegitimate
      recombination between 14-bp microrepeats has separated the genomic TIR sequences
      from the CMS-associated region. Although RNAs containing orf355/orf77 can still
      be detected in the revertants, they are not highly expressed during pollen
      development and they are no longer initiated from the TIR promoter at a protein
      stabilized linear end. They appear instead to be co-transcribed with cytochrome
      oxidase subunit 2. The 7.3-kb inversion was not detected in CMS-S or in other
      fertile revertants. Therefore, this inversion appears to be a de novo mutation
      that has continued to sort out within a single maternal lineage, giving rise to
      fertile progeny in successive generations.

PMID- 21858104
TI  - Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene.
AB  - BACKGROUND: Epidemiological studies have shown that unfiltered coffee consumption
      is associated with a low incidence of cancer. This study aims to identify the
      effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on
      angiogenesis and key inflammatory molecules. METHODOLOGY/PRINCIPAL FINDINGS: The
      experimental procedures included in vivo angiogenesis assays (both the chicken
      and quail choriallantoic membrane assay and the angiogenesis assay with
      fluorescent zebrafish), the ex vivo mouse aortic ring assay and the in vitro
      analysis of the effects of treatment of human endothelial cells with kahweol in
      cell growth, cell viability, cell migration and zymographic assays, as well as
      the tube formation assay on Matrigel. Additionally, two inflammation markers were
      determined, namely, the expression levels of cyclooxygenase 2 and the levels of
      secreted monocyte chemoattractant protein-1. We show for the first time that
      kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and
      one ex vivo angiogenesis models, with effects on specific steps of the angiogenic
      process: endothelial cell proliferation, migration, invasion and tube formation
      on Matrigel. We also demonstrate the inhibitory effect of kahweol on the
      endothelial cell potential to remodel extracellular matrix by targeting two key
      molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory
      potential of this compound is demonstrated by its inhibition of both COX-2
      expression and MCP-1 secretion in endothelial cells. CONCLUSION/SIGNIFICANCE:
      Taken together, our data indicate that, indeed, kahweol behaves as an anti
      inflammatory and anti-angiogenic compound with potential use in antitumoral
      therapies. These data may contribute to the explanation of the reported
      antitumoral effects of kahweol, including the recent epidemiological meta
      analysis showing that drinking coffee could decrease the risk of certain cancers.

PMID- 21858105
TI  - Hox10 genes function in kidney development in the differentiation and integration
      of the cortical stroma.
AB  - Organogenesis requires the differentiation and integration of distinct
      populations of cells to form a functional organ. In the kidney, reciprocal
      interactions between the ureter and the nephrogenic mesenchyme are required for
      organ formation. Additionally, the differentiation and integration of stromal
      cells are also necessary for the proper development of this organ. Much remains
      to be understood regarding the origin of cortical stromal cells and the pathways
      involved in their formation and function. By generating triple mutants in the
      Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical
      role in the developing kidney. Careful examination of control kidneys show that
      Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern
      anterior to the metanephric mesenchyme and these cells subsequently integrate
      posteriorly into the kidney periphery as development proceeds. While the initial
      cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in
      Hox10 mutants, these cells fail to become properly integrated into the kidney,
      and do not differentiate to form the kidney capsule. Consistent with loss of
      cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant
      ureter branching, decreased nephrogenesis. These data therefore provide critical
      novel insights into the cellular and genetic mechanisms governing cortical cell
      development during kidney organogenesis. These results, combined with previous
      evidence demonstrating that Hox11 genes are necessary for patterning the
      metanephric mesenchyme, support a model whereby distinct populations in the
      nephrogenic cord are regulated by unique Hox codes, and that differential Hox
      function along the AP axis of the nephrogenic cord is critical for the
      differentiation and integration of these cell types during kidney organogenesis.

PMID- 21858106
TI  - Impaired vascular contractility and aortic wall degeneration in fibulin-4
      deficient mice: effect of angiotensin II type 1 (AT1) receptor blockade.
AB  - Medial degeneration is a key feature of aneurysm disease and aortic dissection.
      In a murine aneurysm model we investigated the structural and functional
      characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and
      the potential therapeutic role of the angiotensin (Ang) II type 1 (AT(1))
      receptor antagonist losartan in preventing aortic media degeneration. Adult mice
      with 2-fold (heterozygous Fibulin-4(+/R)) and 4-fold (homozygous Fibulin-4(R/R))
      reduced expression of fibulin-4 displayed the histological features of cystic
      media degeneration as found in patients with aneurysm or dissection, including
      elastin fiber fragmentation, loss of smooth muscle cells, and deposition of
      ground substance in the extracellular matrix of the aortic media. The aortic
      contractile capacity, determined by isometric force measurements, was diminished,
      and was associated with dysregulation of contractile genes as shown by aortic
      transcriptome analysis. These structural and functional alterations were
      accompanied by upregulation of TGF-beta signaling in aortas from fibulin-4
      deficient mice, as identified by genome-scaled network analysis as well as by
      immunohistochemical staining for phosphorylated Smad2, an intracellular mediator
      of TGF-beta. Tissue levels of Ang II, a regulator of TGF-beta signaling, were
      increased. Prenatal treatment with the AT(1) receptor antagonist losartan, which
      blunts TGF-beta signaling, prevented elastic fiber fragmentation in the aortic
      media of newborn Fibulin-4(R/R) mice. Postnatal losartan treatment reduced
      haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4
      animals, but did not affect aortic vessel wall structure. In conclusion, the
      AT(1) receptor blocker losartan can prevent aortic media degeneration in a non
      Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan
      does not affect aortic architecture, but does improve survival. These findings
      may extend the potential therapeutic application of inhibitors of the renin
      angiotensin system to the preventive treatment of aneurysm disease.

PMID- 21858107
TI  - Identifying host genetic risk factors in the context of public health
      surveillance for invasive pneumococcal disease.
AB  - Host genetic factors that modify risk of pneumococcal disease may help target
      future public health interventions to individuals at highest risk of disease. We
      linked data from population-based surveillance for invasive pneumococcal disease
      (IPD) with state-based newborn dried bloodspot repositories to identify
      biological samples from individuals who developed invasive pneumococcal disease.
      Genomic DNA was extracted from 366 case and 732 anonymous control samples.
      TagSNPs were selected in 34 candidate genes thought to be associated with host
      response to invasive pneumococcal disease, and a total of 326 variants were
      successfully genotyped. Among 543 European Americans (EA) (182 cases and 361
      controls), and 166 African Americans (AA) (53 cases and 113 controls), common
      variants in surfactant protein D (SFTPD) are consistently underrepresented in
      IPD. SFTPD variants with the strongest association for IPD are intronic
      rs17886286 (allelic OR 0.45, 95% confidence interval (CI) [0.25, 0.82], with p =
      0.007) in EA and 5' flanking rs12219080 (allelic OR 0.32, 95%CI [0.13, 0.78],
      with p = 0.009) in AA. Variants in CD46 and IL1R1 are also associated with IPD in
      both EA and AA, but with effects in different directions; FAS, IL1B, IL4, IL10,
      IL12B, SFTPA1, SFTPB, and PTAFR variants are associated (p<=0.05) with IPD in EA
      or AA. We conclude that variants in SFTPD may protect against IPD in EA and AA
      and genetic variation in other host response pathways may also contribute to risk
      of IPD. While our associations are not corrected for multiple comparisons and
      therefore must be replicated in additional cohorts, this pilot study underscores
      the feasibility of integrating public health surveillance with existing,
      prospectively collected, newborn dried blood spot repositories to identify host
      genetic factors associated with infectious diseases.

PMID- 21858109
TI  - Evidence of an antimicrobial-immunomodulatory role of Atlantic salmon
      cathelicidins during infection with Yersinia ruckeri.
AB  - Cathelicidins are a family of antimicrobial peptides that act as effector
      molecules of the innate immune system with broad-spectrum antimicrobial
      properties. These evolutionary conserved cationic host-defence peptides are
      integral components of the immune response of fish, which are generally believed
      to rely heavily on innate immune defences to invading pathogens. In this study we
      showed that Atlantic salmon cathelicidin 1 and 2 (asCATH1 and asCATH2) stimulated
      peripheral blood leukocytes increasing the transcription of the chemokine
      interleukin-8. Further, functional differences were identified between the two
      cathelicidins. In the presence of serum, asCATH1 displayed greatly diminished
      host haemolytic activity, while the constitutively expressed asCATH2 had no
      haemolytic activity with or without serum. These findings support our hypothesis
      that fish cathelicidins exert their primary antimicrobial action at the site of
      pathogen invasion such as epithelial surfaces. Further, we hypothesise that like
      their mammalian counterparts in the presence of serum they act as mediators of
      the innate and adaptive immune response via the release of cytokines thus
      indirectly protecting against a variety of pathogens. We highlight the importance
      of this immunomodulatory role from the involvement of asCATHs during an infection
      with the fish pathogen Yersinia ruckeri. While we were able to demonstrate in
      vitro that asCATH1 and 2, possessed direct microbicidal activity against the fish
      pathogen, Vibrio anguillarum, and a common gram negative bacterium, Escherichia
      coli, little or no bactericidal activity was found against Y. ruckeri. The
      contribution of either asCATH in the immune response or as a potential virulence
      factor during yersiniosis is highlighted from the increased expression of asCATH1
      and 2 mRNA during an in vivo challenge with Y. ruckeri . We propose that Atlantic
      salmon cathelicidins participate in the interplay between the innate and adaptive
      immune systems via the release of cytokines enabling a more effective response to
      invading pathogens.

PMID- 21858108
TI  - Comparative genomics of multidrug resistance-encoding IncA/C plasmids from
      commensal and pathogenic Escherichia coli from multiple animal sources.
AB  - Incompatibility group A/C (IncA/C) plasmids have received recent attention for
      their broad host range and ability to confer resistance to multiple antimicrobial
      agents. Due to the potential spread of multidrug resistance (MDR) phenotypes from
      foodborne pathogens to human pathogens, the dissemination of these plasmids
      represents a public health risk. In this study, four animal-source IncA/C
      plasmids isolated from Escherichia coli were sequenced and analyzed, including
      isolates from commercial dairy cows, pigs and turkeys in the U.S. and Chile.
      These plasmids were initially selected because they either contained the floR and
      tetA genes encoding for florfenicol and tetracycline resistance, respectively,
      and/or the bla(CMY-2) gene encoding for extended spectrum beta-lactamase
      resistance. Overall, sequence analysis revealed that each of the four plasmids
      retained a remarkably stable and conserved backbone sequence, with differences
      observed primarily within their accessory regions, which presumably have evolved
      via horizontal gene transfer events involving multiple modules. Comparison of
      these plasmids with other available IncA/C plasmid sequences further defined the
      core and accessory elements of these plasmids in E. coli and Salmonella. Our
      results suggest that the bla(CMY-2) plasmid lineage appears to have derived from
      an ancestral IncA/C plasmid type harboring floR-tetAR-strAB and Tn21-like
      accessory modules. Evidence is mounting that IncA/C plasmids are widespread among
      enteric bacteria of production animals and these emergent plasmids have
      flexibility in their acquisition of MDR-encoding modules, necessitating further
      study to understand the evolutionary mechanisms involved in their dissemination
      and stability in bacterial populations.

PMID- 21858110
TI  - On the lack of consensus over the meaning of openness: an empirical study.
AB  - This study set out to explore the views and motivations of those involved in a
      number of recent and current advocacy efforts (such as open science,
      computational provenance, and reproducible research) aimed at making science and
      scientific artifacts accessible to a wider audience. Using a exploratory
      approach, the study tested whether a consensus exists among advocates of these
      initiatives about the key concepts, exploring the meanings that scientists attach
      to the various mechanisms for sharing their work, and the social context in which
      this takes place. The study used a purposive sampling strategy to target
      scientists who have been active participants in these advocacy efforts, and an
      open-ended questionnaire to collect detailed opinions on the topics of
      reproducibility, credibility, scooping, data sharing, results sharing, and the
      effectiveness of the peer review process. We found evidence of a lack of
      agreement on the meaning of key terminology, and a lack of consensus on some of
      the broader goals of these advocacy efforts. These results can be explained
      through a closer examination of the divergent goals and approaches adopted by
      different advocacy efforts. We suggest that the scientific community could
      benefit from a broader discussion of what it means to make scientific research
      more accessible and how this might best be achieved.

PMID- 21858111
TI  - Magnetoacoustic imaging of electrical conductivity of biological tissues at a
      spatial resolution better than 2 mm.
AB  - Magnetoacoustic tomography with magnetic induction (MAT-MI) is an emerging
      approach for noninvasively imaging electrical impedance properties of biological
      tissues. The MAT-MI imaging system measures ultrasound waves generated by the
      Lorentz force, having been induced by magnetic stimulation, which is related to
      the electrical conductivity distribution in tissue samples. MAT-MI promises to
      provide fine spatial resolution for biological tissue imaging as compared to
      ultrasound resolution. In the present study, we first estimated the imaging
      spatial resolution by calculating the full width at half maximum (FWHM) of the
      system point spread function (PSF). The actual spatial resolution of our MAT-MI
      system was experimentally determined to be 1.51 mm by a parallel-line-source
      phantom with Rayleigh criterion. Reconstructed images made from tissue-mimicking
      gel phantoms, as well as animal tissue samples, were consistent with the
      morphological structures of the samples. The electrical conductivity value of the
      samples was determined directly by a calibrated four-electrode system. It has
      been demonstrated that MAT-MI is able to image the electrical impedance
      properties of biological tissues with better than 2 mm spatial resolution. These
      results suggest the potential of MAT-MI for application to early detection of
      small-size diseased tissues (e.g. small breast cancer).

PMID- 21858112
TI  - Landscape ecotoxicology of coho salmon spawner mortality in urban streams.
AB  - In the Pacific Northwest of the United States, adult coho salmon (Oncorhynchus
      kisutch) returning from the ocean to spawn in urban basins of the Puget Sound
      region have been prematurely dying at high rates (up to 90% of the total runs)
      for more than a decade. The current weight of evidence indicates that coho deaths
      are caused by toxic chemical contaminants in land-based runoff to urban streams
      during the fall spawning season. Non-point source pollution in urban landscapes
      typically originates from discrete urban and residential land use activities. In
      the present study we conducted a series of spatial analyses to identify
      correlations between land use and land cover (roadways, impervious surfaces,
      forests, etc.) and the magnitude of coho mortality in six streams with different
      drainage basin characteristics. We found that spawner mortality was most closely
      and positively correlated with the relative proportion of local roads, impervious
      surfaces, and commercial property within a basin. These and other correlated
      variables were used to identify unmonitored basins in the greater Seattle
      metropolitan area where recurrent coho spawner die-offs may be likely. This
      predictive map indicates a substantial geographic area of vulnerability for the
      Puget Sound coho population segment, a species of concern under the U.S.
      Endangered Species Act. Our spatial risk representation has numerous applications
      for urban growth management, coho conservation, and basin restoration (e.g.,
      avoiding the unintentional creation of ecological traps). Moreover, the approach
      and tools are transferable to areas supporting coho throughout western North
      America.

PMID- 21858113
TI  - Berberine radiosensitizes human esophageal cancer cells by downregulating
      homologous recombination repair protein RAD51.
AB  - BACKGROUND: Esophageal squamous cell carcinomas (ESCC) have poor prognosis. While
      combined modality of chemotherapy and radiotherapy increases survival, most
      patients die within five years. Development of agents that confer cancer cell
      specific chemo- and radiosensitivity may improve the therapy of ESCC. We here
      reported the discovery of berberine as a potent radiosensitizing agent on ESCC
      cells. PRINCIPAL FINDINGS: Berberine at low concentrations (<15 uM) substantially
      radiosensitized ESCC cells. X-ray induced DNA double-strand breaks (DSBs) persist
      longer in ESCC cells pretreated with berberine. Berberine pretreatment led to a
      significant downregulation of RAD51, a key player in homologous recombination
      repair, in ESCC cells, but not in non-malignant human cells. Downregulation of
      RAD51 by RNA interference similarly radiosensitized the cancer cells, and,
      conversely, introduction of exogenous RAD51 was able to significantly counteract
      the radiosensitizing effect of berberine, thus establishing RAD51 as a key
      determinant in radiation sensitivity. We also observed that RAD51 was commonly
      overexpressed in human ESCC tissues, suggesting that it is necessary to
      downregulate RAD51 to achieve high radio- or chemotherapeutic efficacy of ESCC in
      clinic, because overexpression of RAD51 is known to confer radio- and
      chemoresistance. CONCLUSIONS/SIGNIFICANCE: Berberine can effectively downregulate
      RAD51 in conferring radiosensitivity on esophageal cancer cells. Its clinical
      application as an adjuvant in chemotherapy and radiotherapy of esophageal cancers
      should be explored.

PMID- 21858114
TI  - beta-Catenin signaling increases during melanoma progression and promotes tumor
      cell survival and chemoresistance.
AB  - Beta-catenin plays an important role in embryogenesis and carcinogenesis by
      controlling either cadherin-mediated cell adhesion or transcriptional activation
      of target gene expression. In many types of cancers nuclear translocation of beta
      catenin has been observed. Our data indicate that during melanoma progression an
      increased dependency on the transcriptional function of beta-catenin takes place.
      Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces
      apoptosis, inhibits proliferation, migration and invasion in monolayer and 3
      dimensional skin reconstructs and decreases chemoresistance. In addition,
      subcutaneous melanoma growth in SCID mice was almost completely inhibited by an
      inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes
      and primary melanoma cell lines was less affected by beta-catenin depletion.
      However, enhanced expression of beta-catenin in primary melanoma cell lines
      increased invasive capacity in vitro and tumor growth in the SCID mouse model.
      These data suggest that beta-catenin is an essential survival factor for
      metastatic melanoma cells, whereas it is dispensable for the survival of benign
      melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin
      increases tumorigenicity of primary melanoma cell lines. The differential
      requirements for beta-catenin signaling in aggressive melanoma versus benign
      melanocytic cells make beta-catenin a possible new target in melanoma therapy.

PMID- 21858116
TI  - Onset of quiescence following p53 mediated down-regulation of H2AX in normal
      cells.
AB  - Normal cells, both in vivo and in vitro, become quiescent after serial cell
      proliferation. During this process, cells can develop immortality with genomic
      instability, although the mechanisms by which this is regulated are unclear.
      Here, we show that a growth-arrested cellular status is produced by the down
      regulation of histone H2AX in normal cells. Normal mouse embryonic fibroblast
      cells preserve an H2AX diminished quiescent status through p53 regulation and
      stable-diploidy maintenance. However, such quiescence is abrogated under
      continuous growth stimulation, inducing DNA replication stress. Because DNA
      replication stress-associated lesions are cryptogenic and capable of mediating
      chromosome-bridge formation and cytokinesis failure, this results in
      tetraploidization. Arf/p53 module-mutation is induced during tetraploidization
      with the resulting H2AX recovery and immortality acquisition. Thus, although
      cellular homeostasis is preserved under quiescence with stable diploidy,
      tetraploidization induced under growth stimulation disrupts the homeostasis and
      triggers immortality acquisition.

PMID- 21858115
TI  - Plasmodium falciparum: differential selection of drug resistance alleles in
      contiguous urban and peri-urban areas of Brazzaville, Republic of Congo.
AB  - The African continent is currently experiencing rapid population growth, with
      rising urbanization increasing the percentage of the population living in large
      towns and cities. We studied the impact of the degree of urbanization on the
      population genetics of Plasmodium falciparum in urban and peri-urban areas in and
      around the city of Brazzaville, Republic of Congo. This field setting, which
      incorporates local health centers situated in areas of varying urbanization, is
      of interest as it allows the characterization of malaria parasites from areas
      where the human, parasite, and mosquito populations are shared, but where
      differences in the degree of urbanization (leading to dramatic differences in
      transmission intensity) cause the pattern of malaria transmission to differ
      greatly. We have investigated how these differences in transmission intensity
      affect parasite genetic diversity, including the amount of genetic polymorphism
      in each area, the degree of linkage disequilibrium within the populations, and
      the prevalence and frequency of drug resistance markers. To determine parasite
      population structure, heterozygosity and linkage disequilibrium, we typed eight
      microsatellite markers and performed haplotype analysis of the msp1 gene by PCR.
      Mutations known to be associated with resistance to the antimalarial drugs
      chloroquine and pyrimethamine were determined by sequencing the relevant portions
      of the crt and dhfr genes, respectively. We found that parasite genetic diversity
      was comparable between the two sites, with high levels of polymorphism being
      maintained in both areas despite dramatic differences in transmission intensity.
      Crucially, we found that the frequencies of genetic markers of drug resistance
      against pyrimethamine and chloroquine differed significantly between the sites,
      indicative of differing selection pressures in the two areas.

PMID- 21858117
TI  - Exogenous HIV-1 Nef upsets the IFN-gamma-induced impairment of human intestinal
      epithelial integrity.
AB  - BACKGROUND: The mucosal tissues play a central role in the transmission of HIV-1
      infection as well as in the pathogenesis of AIDS. Despite several clinical
      studies reported intestinal dysfunction during HIV infection, the mechanisms
      underlying HIV-induced impairments of mucosal epithelial barrier are still
      unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1
      proteins have been detected in several cell types of the intestinal mucosa. In
      the present study, we analyzed the effect of the accessory HIV-1 Nef protein on
      human epithelial cell line. METHODOLOGY/PRINCIPAL FINDINGS: We used unstimulated
      or IFN-gamma-stimulated Caco-2 cells, as a model for homeostatic and inflamed
      gastrointestinal tracts, respectively. We investigated the effect of exogenous
      recombinant Nef on monolayer integrity analyzing its uptake, transepithelial
      electrical resistance, permeability to FITC-dextran and the expression of tight
      junction proteins. Moreover, we measured the induction of proinflammatory
      mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal
      epithelial permeability and upset the IFN-gamma-induced reduction of
      transepithelial resistance, interfering with tight junction protein expression.
      Moreover, Nef inhibited IFN-gamma-induced apoptosis and up-regulated TNF-alpha,
      IL-6 and MIP-3alpha production by Caco-2 cells while down-regulated IL-10
      production. The simultaneous exposure of Caco-2 cells to Nef and IFN-gamma did
      not affect cytokine secretion respect to untreated cells. Finally, we found that
      Nef counteracted the IFN-gamma induced arachidonic acid cascade.
      CONCLUSION/SIGNIFICANCE: Our findings suggest that exogenous Nef, perturbing the
      IFN-gamma-induced impairment of intestinal epithelial cells, could prolong cell
      survival, thus allowing for accumulation of viral particles. Our results may
      improve the understanding of AIDS pathogenesis, supporting the discovery of new
      therapeutic interventions.

PMID- 21858118
TI  - Effect of the H1N1 influenza pandemic on the incidence of epidemic
      keratoconjunctivitis and on hygiene behavior: a cross-sectional study.
AB  - BACKGROUND: EKC is transmitted chiefly by direct hand contact. It is suspected
      that the 2009/2010 influenza pandemic influenced hand washing. This study aims to
      examine the relationship between the 2009/2010 H1N1 influenza pandemic and
      hygiene behavior. METHODS: We compared the EKC prevalence trends before, during
      and after the 2009/2010 influenza pandemic by using a t-test comparison of EKC
      sentinel surveillance. RESULTS: During the pre-pandemic period, the incidence of
      EKC increased from the 21st to the 44th week each year. However, during the
      pandemic period in 2009, there was no epidemic peak. In the post-pandemic period,
      the epidemic curve was similar to that in the pre-pandemic period. Compared to
      the pre-pandemic period, the total number of EKC patients during the pandemic
      period showed a decrease of 44.9% (t value = -7.23, p = 0.002). Comparing the pre
      pandemic and pandemic periods by age group, we found there to be a significant
      decrease in the number of EKC patients for all age groups (-4.12<=t value<=-7.23,
      all P<0.05). This finding was most evident in the teenage group (62%) compared to
      the other age groups (decreases of 29 to 44%). CONCLUSIONS: A continuing effort
      should be made to educate the public on basic infection prevention behaviors in
      the aftermath of the pandemic, particularly to teenagers.

PMID- 21858119
TI  - Tree resin composition, collection behavior and selective filters shape chemical
      profiles of tropical bees (Apidae: Meliponini).
AB  - The diversity of species is striking, but can be far exceeded by the chemical
      diversity of compounds collected, produced or used by them. Here, we relate the
      specificity of plant-consumer interactions to chemical diversity applying a
      comparative network analysis to both levels. Chemical diversity was explored for
      interactions between tropical stingless bees and plant resins, which bees collect
      for nest construction and to deter predators and microbes. Resins also function
      as an environmental source for terpenes that serve as appeasement allomones and
      protection against predators when accumulated on the bees' body surfaces. To
      unravel the origin of the bees' complex chemical profiles, we investigated resin
      collection and the processing of resin-derived terpenes. We therefore analyzed
      chemical networks of tree resins, foraging networks of resin collecting bees, and
      their acquired chemical networks. We revealed that 113 terpenes in nests of six
      bee species and 83 on their body surfaces comprised a subset of the 1,117
      compounds found in resins from seven tree species. Sesquiterpenes were the most
      variable class of terpenes. Albeit widely present in tree resins, they were only
      found on the body surface of some species, but entirely lacking in others.
      Moreover, whereas the nest profile of Tetragonula melanocephala contained
      sesquiterpenes, its surface profile did not. Stingless bees showed a generalized
      collecting behavior among resin sources, and only a hitherto undescribed species
      specific "filtering" of resin-derived terpenes can explain the variation in
      chemical profiles of nests and body surfaces from different species. The tight
      relationship between bees and tree resins of a large variety of species
      elucidates why the bees' surfaces contain a much higher chemodiversity than other
      hymenopterans.

PMID- 21858120
TI  - The Potorous CPD photolyase rescues a cryptochrome-deficient mammalian circadian
      clock.
AB  - Despite the sequence and structural conservation between cryptochromes and
      photolyases, members of the cryptochrome/photolyase (flavo)protein family, their
      functions are divergent. Whereas photolyases are DNA repair enzymes that use
      visible light to lesion-specifically remove UV-induced DNA damage, cryptochromes
      act as photoreceptors and circadian clock proteins. To address the functional
      diversity of cryptochromes and photolyases, we investigated the effect of
      ectopically expressed Arabidopsis thaliana (6-4)PP photolyase and Potorous
      tridactylus CPD-photolyase (close and distant relatives of mammalian
      cryptochromes, respectively), on the performance of the mammalian cryptochromes
      in the mammalian circadian clock. Using photolyase transgenic mice, we show that
      Potorous CPD-photolyase affects the clock by shortening the period of behavioral
      rhythms. Furthermore, constitutively expressed CPD-photolyase is shown to reduce
      the amplitude of circadian oscillations in cultured cells and to inhibit
      CLOCK/BMAL1 driven transcription by interacting with CLOCK. Importantly, we show
      that Potorous CPD-photolyase can restore the molecular oscillator in the liver of
      (clock-deficient) Cry1/Cry2 double knockout mice. These data demonstrate that a
      photolyase can act as a true cryptochrome. These findings shed new light on the
      importance of the core structure of mammalian cryptochromes in relation to its
      function in the circadian clock and contribute to our further understanding of
      the evolution of the cryptochrome/photolyase protein family.

PMID- 21858121
TI  - Opposing effects of the angiopoietins on the thrombin-induced permeability of
      human pulmonary microvascular endothelial cells.
AB  - BACKGROUND: Angiopoietin-2 (Ang-2) is associated with lung injury in ALI/ARDS. As
      endothelial activation by thrombin plays a role in the permeability of acute lung
      injury and Ang-2 may modulate the kinetics of thrombin-induced permeability by
      impairing the organization of vascular endothelial (VE-)cadherin, and affecting
      small Rho GTPases in human pulmonary microvascular endothelial cells (HPMVECs),
      we hypothesized that Ang-2 acts as a sensitizer of thrombin-induced
      hyperpermeability of HPMVECs, opposed by Ang-1. METHODOLOGY/PRINCIPAL FINDINGS:
      Permeability was assessed by measuring macromolecule passage and transendothelial
      electrical resistance (TEER). Angiopoietins did not affect basal permeability.
      Nevertheless, they had opposing effects on the thrombin-induced permeability, in
      particular in the initial phase. Ang-2 enhanced the initial permeability increase
      (passage, P = 0.010; TEER, P = 0.021) in parallel with impairment of VE-cadherin
      organization without affecting VE-cadherin Tyr685 phosphorylation or increasing
      RhoA activity. Ang-2 also increased intercellular gap formation. Ang-1
      preincubation increased Rac1 activity, enforced the VE-cadherin organization,
      reduced the initial thrombin-induced permeability (TEER, P = 0.027), while Rac1
      activity simultaneously normalized, and reduced RhoA activity at 15 min thrombin
      exposure (P = 0.039), but not at earlier time points. The simultaneous presence
      of Ang-2 largely prevented the effect of Ang-1 on TEER and macromolecule passage.
      CONCLUSIONS/SIGNIFICANCE: Ang-1 attenuated thrombin-induced permeability, which
      involved initial Rac1 activation-enforced cell-cell junctions, and later RhoA
      inhibition. In addition to antagonizing Ang-1, Ang-2 had also a direct effect
      itself. Ang-2 sensitized the initial thrombin-induced permeability accompanied by
      destabilization of VE-cadherin junctions and increased gap formation, in the
      absence of increased RhoA activity.

PMID- 21858122
TI  - Preterm delivery disrupts the developmental program of the cerebellum.
AB  - A rapid growth in human cerebellar development occurs in the third trimester,
      which is impeded by preterm delivery. The goal of this study was to characterize
      the impact of preterm delivery on the developmental program of the human
      cerebellum. Still born infants, which meant that all development up to that age
      had taken place in-utero, were age paired with preterm delivery infants, who had
      survived in an ex-utero environment, which meant that their development had also
      taken place outside the uterus. The two groups were assessed on quantitative
      measures that included molecular markers of granule neuron, purkinje neuron and
      bergmann glia differentiation, as well as the expression of the sonic hedgehog
      signaling pathway, that is important for cerebellar growth. We report that
      premature birth and development in an ex-utero environment leads to a significant
      decrease in the thickness and an increase in the packing density of the cells
      within the external granular layer and the inner granular layer well, as a
      reduction in the density of bergmann glial fibres. In addition, this also leads
      to a reduced expression of sonic hedgehog in the purkinje layer. We conclude that
      the developmental program of the cerebellum is specifically modified by events
      that follow preterm delivery.

PMID- 21858123
TI  - Impact of Schistosoma japonicum infection on collagen-induced arthritis in DBA/1
      mice: a murine model of human rheumatoid arthritis.
AB  - BACKGROUND: The hygiene hypothesis suggests that helminth infections prevent a
      range of autoimmune diseases. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the
      effects of S. japonicum infection on collagen-induced arthritis (CIA), male DBA/1
      mice were challenged with unisexual or bisexual S. japonicum cercariae two weeks
      prior to bovine type II collagen (CII) immunization or at the onset of CIA. S.
      japonicum infection prior to CII immunization significantly reduced the severity
      of CIA. ELISA (enzyme linked immunosorbent assay) showed that the levels of anti
      CII IgG and IgG2a were reduced in prior schistosome-infected mice, while anti-CII
      IgG1 was elevated. Splenocyte proliferation against both polyclonal and antigen
      specific stimuli was reduced by prior schistosome infection as measured by
      tritiated thymidine incorporation ((3)H-TdR). Cytokine profiles and CD4(+) T
      cells subpopulation analysis by ELISA and flow cytometry (FCM) demonstrated that
      prior schistosome infection resulted in a significant down-regulation of pro
      inflammatory cytokines (IFN-gamma, TNF-alpha, IL-1beta and IL-6) and Th1 cells,
      together with up-regulation of the anti-inflammatory cytokine IL-10 and Th2
      cells. Interestingly, the expansion of Treg cells and the reduction of Th17 cells
      were only observed in bisexually infected mice. In addition, prior schistosome
      infection notably reduced the expression of pro-inflammatory cytokines and
      receptor activator of NF-kappaB ligand (RANKL) in the inflamed joint. However,
      the disease was exacerbated at one week after infection when established CIA mice
      were challenged with bisexual cercariae. CONCLUSION/SIGNIFICANCE: Our data
      provide direct evidence that the Th2 response evoked by prior S. japonicum
      infection can suppress the Th1 response and pro-inflammatory mediator and that
      bisexual infection with egg-laying up-regulates the Treg response and down
      regulates the Th17 response, resulting in an amelioration of autoimmune
      arthritis. The beneficial effects might depend on the establishment of a Th2
      dominant response rather than the presence of the eggs. Our results suggest that
      anti-inflammatory molecules from the parasite could treat autoimmune diseases.

PMID- 21858124
TI  - Phylodynamics and molecular evolution of influenza A virus nucleoprotein genes in
      Taiwan between 1979 and 2009.
AB  - BACKGROUND: Many studies concentrate on variation in the hemagglutinin
      glycoprotein (HA) because of its significance in host immune response, the
      evolution of this virus is even more complex when other genome segments are
      considered. Recently, it was found that cytotoxic T lymphocytes (CTL) play an
      important role in immunity against influenza and most CTL epitopes of human
      influenza viruses were remarkably conserved. The NP gene has evolved
      independently in human and avian hosts after 1918 flu pandemic and it has been
      assigned a putative role as a determinant of host range. METHODS AND FINDINGS:
      Phylodynamic patterns of the genes encoding nucleoprotein (NP) of influenza A
      viruses isolated from 1979-2009 were analyzed by applying the Bayesian Markov
      Chain Monte Carlo framework to better understand the evolutionary mechanisms of
      these Taiwanese isolates. Phylogenetic analysis of the NP gene showed that all
      available H3 worldwide isolates collected so far were genetically similar and
      divided into two major clades after the year 2004. We compared the deduced amino
      acid sequences of the NP sequences from human, avian and swine hosts to
      investigate the emergence of potential adaptive mutations. Overall, selective
      pressure on the NP gene of human influenza A viruses appeared to be dominated by
      purifying selection with a mean d(N)/d(S) ratio of 0.105. Site-selection analysis
      of 488 codons, however, also revealed 3 positively selected sites in addition to
      139 negatively selected ones. CONCLUSIONS: The demographic history inferred by
      Bayesian skyline plot showed that the effective number of infections underwent a
      period of smooth and steady growth from 1998 to 2001, followed by a more recent
      rise in the rate of spread. Further understanding the correlates of interspecies
      transmission of influenza A virus genes from other host reservoirs to the human
      population may help to elucidate the mechanisms of variability among influenza A
      virus.

PMID- 21858125
TI  - LOCAS--a low coverage assembly tool for resequencing projects.
AB  - MOTIVATION: Next Generation Sequencing (NGS) is a frequently applied approach to
      detect sequence variations between highly related genomes. Recent large-scale re
      sequencing studies as the Human 1000 Genomes Project utilize NGS data of low
      coverage to afford sequencing of hundreds of individuals. Here, SNPs and micro
      indels can be detected by applying an alignment-consensus approach. However,
      computational methods capable of discovering other variations such as novel
      insertions or highly diverged sequence from low coverage NGS data are still
      lacking. RESULTS: We present LOCAS, a new NGS assembler particularly designed for
      low coverage assembly of eukaryotic genomes using a mismatch sensitive overlap
      layout-consensus approach. LOCAS assembles homologous regions in a homology
      guided manner while it performs de novo assemblies of insertions and highly
      polymorphic target regions subsequently to an alignment-consensus approach. LOCAS
      has been evaluated in homology-guided assembly scenarios with low sequence
      coverage of Arabidopsis thaliana strains sequenced as part of the Arabidopsis
      1001 Genomes Project. While assembling the same amount of long insertions as
      state-of-the-art NGS assemblers, LOCAS showed best results regarding contig size,
      error rate and runtime. CONCLUSION: LOCAS produces excellent results for homology
      guided assembly of eukaryotic genomes with short reads and low sequencing depth,
      and therefore appears to be the assembly tool of choice for the detection of
      novel sequence variations in this scenario.

PMID- 21858126
TI  - A one-step miniprep for the isolation of plasmid DNA and lambda phage particles.
AB  - Plasmid DNA minipreps are fundamental techniques in molecular biology. Current
      plasmid DNA minipreps use alkali and the anionic detergent SDS in a three
      solution format. In addition, alkali minipreps usually require additional column
      based purification steps and cannot isolate other extra-chromosomal elements,
      such as bacteriophages. Non-ionic detergents (NIDs) have been used occasionally
      as components of multiple-solution plasmid DNA minipreps, but a one-step approach
      has not been developed. Here, we have established a one-tube, one-solution NID
      plasmid DNA miniprep, and we show that this approach also isolates bacteriophage
      lambda particles. NID minipreps are more time-efficient than alkali minipreps,
      and NID plasmid DNA performs better than alkali DNA in many downstream
      applications. In fact, NID crude lysate DNA is sufficiently pure to be used in
      digestion and sequencing reactions. Microscopic analysis showed that the NID
      procedure fragments E. coli cells into small protoplast-like components, which
      may, at least in part, explain the effectiveness of this approach. This work
      demonstrates that one-step NID minipreps are a robust method to generate high
      quality plasmid DNA, and NID approaches can also isolate bacteriophage lambda
      particles, outperforming current standard alkali-based minipreps.

PMID- 21858127
TI  - No evidence of association between HIV-1 and malaria in populations with low HIV
      1 prevalence.
AB  - BACKGROUND: The geographic overlap between HIV-1 and malaria has generated much
      interest in their potential interactions. A variety of studies have evidenced a
      complex HIV-malaria interaction within individuals and populations that may have
      dramatic effects, but the causes and implications of this co-infection at the
      population level are still unclear. In a previous publication, we showed that the
      prevalence of malaria caused by the parasite Plasmodium falciparum is associated
      with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of
      the HIV-malaria co-infection, the objective of this work was to assess the
      relationship between malaria and HIV prevalence in the western region of sub
      Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: Population-based cross-sectional
      data were obtained from the HIV/AIDS Demographic and Health Surveys conducted in
      Burkina Faso, Ghana, Guinea, Mali, Liberia and Cameroon, and the malaria atlas
      project. Using generalized linear mixed models, we assessed the relationship
      between HIV-1 and Plasmodium falciparum parasite rate (PfPR) adjusting for
      important socio-economic and biological cofactors. We found no evidence that
      individuals living in areas with stable malaria transmission (PfPR>0.46) have
      higher odds of being HIV-positive than individuals who live in areas with
      PfPR<=0.46 in western sub-Saharan Africa (estimated odds ratio 1.14, 95%
      confidence interval 0.86-1.50). In contrast, the results suggested that PfPR was
      associated with being infected with HIV in Cameroon (estimated odds ratio 1.56,
      95% confidence interval 1.23-2.00). CONCLUSION/SIGNIFICANCE: Contrary to our
      previous research on eastern sub-Saharan Africa, this study did not identify an
      association between PfPR and infection with HIV in western sub-Saharan Africa,
      which suggests that malaria might not play an important role in the spread of HIV
      in populations where the HIV prevalence is low. Our work highlights the
      importance of understanding the epidemiologic effect of co-infection and the
      relevant factors involved in this relationship for the implementation of
      effective control strategies.

PMID- 21858128
TI  - Changing bee and hoverfly pollinator assemblages along an urban-rural gradient.
AB  - BACKGROUND: The potential for reduced pollination ecosystem service due to global
      declines of bees and other pollinators is cause for considerable concern. Habitat
      degradation, destruction and fragmentation due to agricultural intensification
      have historically been the main causes of this pollinator decline. However,
      despite increasing and accelerating levels of global urbanization, very little
      research has investigated the effects of urbanization on pollinator assemblages.
      We assessed changes in the diversity, abundance and species composition of bee
      and hoverfly pollinator assemblages in urban, suburban, and rural sites across a
      UK city. METHODOLOGY/PRINCIPAL FINDINGS: Bees and hoverflies were trapped and
      netted at 24 sites of similar habitat character (churchyards and cemeteries) that
      varied in position along a gradient of urbanization. Local habitat quality
      (altitude, shelter from wind, diversity and abundance of flowers), and the
      broader-scale degree of urbanization (e.g. percentage of built landscape and
      gardens within 100 m, 250 m, 500 m, 1 km, and 2.5 km of the site) were assessed
      for each study site. The diversity and abundance of pollinators were both
      significantly negatively associated with higher levels of urbanization.
      Assemblage composition changed along the urbanization gradient with some species
      positively associated with urban and suburban land-use, but more species
      negatively so. Pollinator assemblages were positively affected by good site
      habitat quality, in particular the availability of flowering plants.
      CONCLUSIONS/SIGNIFICANCE: Our results show that urban areas can support diverse
      pollinator assemblages, but that this capacity is strongly affected by local
      habitat quality. Nonetheless, in both urban and suburban areas of the city the
      assemblages had fewer individuals and lower diversity than similar rural
      habitats. The unique development histories of different urban areas, and the
      difficulty of assessing mobile pollinator assemblages in just part of their
      range, mean that complementary studies in different cities and urban habitats are
      required to discover if these findings are more widely applicable.

PMID- 21858130
TI  - Widowhood and mortality: a meta-analysis.
AB  - BACKGROUND: While the "widowhood effect" is well known, there is substantial
      heterogeneity in the magnitude of effects reported in different studies. We
      conducted a meta-analysis of widowhood and mortality, focusing on longitudinal
      studies with follow-up from the time of bereavement. METHODS AND FINDINGS: A
      random-effects meta-analysis was conducted to calculate the overall relative risk
      (RR) for subsequent mortality among 2,263,888 subjects from 15 prospective cohort
      studies. We found a statistically significant positive association between
      widowhood and mortality, but the widowhood effect was stronger in the period
      earlier than six months since bereavement (overall RR = 1.41, 95% CI: 1.26, 1.57)
      compared to the effect after six months (overall RR = 1.14, 95% CI: 1.10, 1.18).
      Meta-regression showed that the widowhood effect was not different for those aged
      younger than 65 years compared to those older than 65 (P = 0.25). There was,
      however, a difference in the magnitude of the widowhood effect by gender; for
      women the RR was not statistically significantly different from the null (overall
      RR = 1.04, 95% CI: 1.00, 1.08), while it was for men (overall RR = 1.23, 95% CI:
      1.18, 1.28). CONCLUSIONS: The results suggest that further studies should focus
      more on the mechanisms that generate this association especially among men.

PMID- 21858129
TI  - Driving and driven architectures of directed small-world human brain functional
      networks.
AB  - Recently, increasing attention has been focused on the investigation of the human
      brain connectome that describes the patterns of structural and functional
      connectivity networks of the human brain. Many studies of the human connectome
      have demonstrated that the brain network follows a small-world topology with an
      intrinsically cohesive modular structure and includes several network hubs in the
      medial parietal regions. However, most of these studies have only focused on
      undirected connections between regions in which the directions of information
      flow are not taken into account. How the brain regions causally influence each
      other and how the directed network of human brain is topologically organized
      remain largely unknown. Here, we applied linear multivariate Granger causality
      analysis (GCA) and graph theoretical approaches to a resting-state functional MRI
      dataset with a large cohort of young healthy participants (n = 86) to explore
      connectivity patterns of the population-based whole-brain functional directed
      network. This directed brain network exhibited prominent small-world properties,
      which obviously improved previous results of functional MRI studies showing weak
      small-world properties in the directed brain networks in terms of a kernel-based
      GCA and individual analysis. This brain network also showed significant modular
      structures associated with 5 well known subsystems: fronto-parietal, visual,
      paralimbic/limbic, subcortical and primary systems. Importantly, we identified
      several driving hubs predominantly located in the components of the attentional
      network (e.g., the inferior frontal gyrus, supplementary motor area, insula and
      fusiform gyrus) and several driven hubs predominantly located in the components
      of the default mode network (e.g., the precuneus, posterior cingulate gyrus,
      medial prefrontal cortex and inferior parietal lobule). Further split-half
      analyses indicated that our results were highly reproducible between two
      independent subgroups. The current study demonstrated the directions of
      spontaneous information flow and causal influences in the directed brain
      networks, thus providing new insights into our understanding of human brain
      functional connectome.

PMID- 21858131
TI  - Transcriptome analysis of potato leaves expressing the trehalose-6-phosphate
      synthase 1 gene of yeast.
AB  - Transgenic lines of the potato cultivar White Lady expressing the trehalose-6
      phosphate synthase (TPS1) gene of yeast exhibit improved drought tolerance, but
      grow slower and have a lower carbon fixation rate and stomatal density than the
      wild-type. To understand the molecular basis of this phenomenon, we have compared
      the transcriptomes of wild-type and TPS1-transgenic plants using the POCI
      microarray containing 42,034 potato unigene probes. We show that 74 and 25 genes
      were up-, and down-regulated, respectively, in the mature source leaves of TPS1
      transgenic plants when compared with the wild-type. The differentially regulated
      genes were assigned into 16 functional groups. All of the seven genes, which were
      assigned into carbon fixation and metabolism group, were up-regulated, while
      about 42% of the assigned genes are involved in transcriptional and post
      transcriptional regulation. Expression of genes encoding a 14-3-3 regulatory
      protein, and four transcription factors were down-regulated in the TPS1
      transgenic leaves. To verify the microarray results, we used RNA gel blot
      analysis to examine the expression of eight genes and found that the RNA gel blot
      and microarray data correlated in each case. Using the putative Arabidopsis
      orthologs of the assigned potato sequences we have identified putative
      transcription binding sites in the promoter region of the differentially
      regulated genes, and putative protein-protein interactions involving some of the
      up- and down-regulated genes. We have also demonstrated that starch content is
      lower, while malate, inositol and maltose contents are higher in the TPS1
      transgenic than in the wild-type leaves. Our results suggest that a complex
      regulatory network, involving transcription factors and other regulatory
      proteins, underpins the phenotypic alterations we have observed previously in
      potato when expressing the TPS1 gene of yeast.

PMID- 21858132
TI  - Human pathogen shown to cause disease in the threatened eklhorn coral Acropora
      palmata.
AB  - Coral reefs are in severe decline. Infections by the human pathogen Serratia
      marcescens have contributed to precipitous losses in the common Caribbean elkhorn
      coral, Acropora palmata, culminating in its listing under the United States
      Endangered Species Act. During a 2003 outbreak of this coral disease, called
      acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens
      strain PDR60, was identified from diseased A. palmata, human wastewater, the non
      host coral Siderastrea siderea and the corallivorous snail Coralliophila
      abbreviata. In order to examine humans as a source and other marine invertebrates
      as vectors and/or reservoirs of the APS pathogen, challenge experiments were
      conducted with A. palmata maintained in closed aquaria to determine infectivity
      of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater
      and diseased A. palmata caused disease signs in elkhorn coral in as little as
      four and five days, respectively, demonstrating that wastewater is a definitive
      source of APS and identifying human strain PDR60 as a coral pathogen through
      fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C.
      abbreviata showed limited virulence, with one of three inoculated fragments
      developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea
      showed a delayed pathogenic effect, with disease signs developing within an
      average of 20 days. These results suggest that C. abbreviata and non-host corals
      may function as reservoirs or vectors of the APS pathogen. Our results provide
      the first example of a marine "reverse zoonosis" involving the transmission of a
      human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These
      findings underscore the interaction between public health practices and
      environmental health indices such as coral reef survival.

PMID- 21858133
TI  - Disparate associations of HLA class I markers with HIV-1 acquisition and control
      of viremia in an African population.
AB  - BACKGROUND: Acquisition of human immunodeficiency virus type 1 (HIV-1) infection
      is mediated by a combination of characteristics of the infectious and the
      susceptible member of a transmission pair, including human behavioral and genetic
      factors, as well as viral fitness and tropism. Here we report on the impact of
      established and potential new HLA class I determinants of heterosexual HIV-1
      acquisition in the HIV-1-exposed seronegative (HESN) partners of serodiscordant
      Zambian couples. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the relationships of
      behavioral and clinically documented risk factors, index partner viral load, and
      host genetic markers to HIV-1 transmission among 568 cohabiting couples followed
      for at least nine months. We genotyped subjects for three classical HLA class I
      genes known to influence immune control of HIV-1 infection. From 1995 to December
      2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional
      hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were
      significantly and independently associated with faster HIV-1 acquisition
      (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively) after
      controlling for other previously established contributing factors in the index
      partner (viral load and specific class I alleles), in the HESN partner (age,
      gender), or in the couple (behavioral and clinical risk score). Few if any
      previously implicated class I markers were associated here with the rate of
      acquiring infection. CONCLUSIONS/SIGNIFICANCE: A few HLA class I markers showed
      modest effects on acquisition of HIV-1 subtype C infection in HESN partners of
      discordant Zambian couples. However, the striking disparity between those few
      markers and the more numerous, different markers found to determine HIV-1 disease
      course makes it highly unlikely that, whatever the influence of class I variation
      on the rate of infection, the mechanism mediating that phenomenon is identical to
      that involved in disease control.

PMID- 21858135
TI  - Efficient replication of over 180 genetic associations with self-reported medical
      data.
AB  - While the cost and speed of generating genomic data have come down dramatically
      in recent years, the slow pace of collecting medical data for large cohorts
      continues to hamper genetic research. Here we evaluate a novel online framework
      for obtaining large amounts of medical information from a recontactable cohort by
      assessing our ability to replicate genetic associations using these data. Using
      web-based questionnaires, we gathered self-reported data on 50 medical phenotypes
      from a generally unselected cohort of over 20,000 genotyped individuals. Of a
      list of genetic associations curated by NHGRI, we successfully replicated about
      75% of the associations that we expected to (based on the number of cases in our
      cohort and reported odds ratios, and excluding a set of associations with
      contradictory published evidence). Altogether we replicated over 180 previously
      reported associations, including many for type 2 diabetes, prostate cancer,
      cholesterol levels, and multiple sclerosis. We found significant variation across
      categories of conditions in the percentage of expected associations that we were
      able to replicate, which may reflect systematic inflation of the effects in some
      initial reports, or differences across diseases in the likelihood of misdiagnosis
      or misreport. We also demonstrated that we could improve replication success by
      taking advantage of our recontactable cohort, offering more in-depth questions to
      refine self-reported diagnoses. Our data suggest that online collection of self
      reported data from a recontactable cohort may be a viable method for both broad
      and deep phenotyping in large populations.

PMID- 21858134
TI  - The role of RamA on the development of ciprofloxacin resistance in Salmonella
      enterica serovar Typhimurium.
AB  - Active efflux pump is a primary fluoroquinolone resistant mechanism of clinical
      isolates of Salmonella enterica serovar Typhimurium. RamA is an essential element
      in producing multidrug resistant (MDR) S. enterica serovar Typhimurium. The aim
      of the present study was to elucidate the roles of RamA on the development of
      ciprofloxacin, the first choice for the treatment of salmonellosis, resistance in
      S. enterica serovar Typhimurium. Spontaneous mutants were selected via several
      passages of S. enterica serovar Typhimurium CVCC541 susceptible strain (ST) on M
      H agar with increasing concentrations of ciprofloxacin (CIP). Accumulation of
      ciprofloxacin was tested by the modified fluorometric method. The expression
      levels of MDR efflux pumps were determined by real time RT-PCR. In ST and its
      spontaneous mutants, the ramA gene was inactivated by insertion of the kan gene
      and compensated on a recombinant plasmid pGEXPhi(gst-ramA). The mutant prevention
      concentration (MPC) and mutant frequencies of ciprofloxacin against ST and a
      spontaneous mutant in the presence, absence and overexpression of RamA were
      tested. Four spontaneous mutants (SI1-SI4) were obtained. The SI1 (CIP MICs, 0.1
      mg/L) without any target site mutation in its quinolone resistant determining
      regions (QRDRs) and SI3 (CIP MICs, 16 mg/L) harboring the Ser83->Phe mutation in
      its QRDR of GyrA strains exhibited reduced susceptibility and resistance to
      multidrugs, respectively. In SI1, RamA was the main factor that controlled the
      susceptibility to ciprofloxacin by activating MdtK as well as increasing the
      expression level of acrAB. In SI3, RamA played predominant role in ciprofloxacin
      resistance via increasing the expression level of acrAB. Likewise, the deficiency
      of RamA decreased the MPCs and mutant frequencies of ST and SI2 to ciprofloxacin.
      In conclusion, the expression of RamA promoted the development of ciprofloxacin
      resistant mutants of S. enterica serovar Typhimurium. The inhibition of RamA
      could decrease the appearance of the ciprofloxacin resistant mutants.

PMID- 21858136
TI  - Expression of PROKR1 and PROKR2 in human enteric neural precursor cells and
      identification of sequence variants suggest a role in HSCR.
AB  - BACKGROUND: The enteric nervous system (ENS) is entirely derived from neural
      crest and its normal development is regulated by specific molecular pathways.
      Failure in complete ENS formation results in aganglionic gut conditions such as
      Hirschsprung's disease (HSCR). Recently, PROKR1 expression has been demonstrated
      in mouse enteric neural crest derived cells and Prok-1 was shown to work
      coordinately with GDNF in the development of the ENS. PRINCIPAL FINDINGS: In the
      present report, ENS progenitors were isolated and characterized from the
      ganglionic gut from children diagnosed with and without HSCR, and the expression
      of prokineticin receptors was examined. Immunocytochemical analysis of
      neurosphere-forming cells demonstrated that both PROKR1 and PROKR2 were present
      in human enteric neural crest cells. In addition, we also performed a mutational
      analysis of PROKR1, PROKR2, PROK1 and PROK2 genes in a cohort of HSCR patients,
      evaluating them for the first time as susceptibility genes for the disease.
      Several missense variants were detected, most of them affecting highly conserved
      amino acid residues of the protein and located in functional domains of both
      receptors, which suggests a possible deleterious effect in their biological
      function. CONCLUSIONS: Our results suggest that not only PROKR1, but also PROKR2
      might mediate a complementary signalling to the RET/GFRalpha1/GDNF pathway
      supporting proliferation/survival and differentiation of precursor cells during
      ENS development. These findings, together with the detection of sequence variants
      in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in
      combination with RET or GDNF mutations, provide the first evidence to consider
      them as susceptibility genes for HSCR.

PMID- 21858137
TI  - Uniform selection as a primary force reducing population genetic differentiation
      of cavitation resistance across a species range.
AB  - BACKGROUND: Cavitation resistance to water stress-induced embolism determines
      plant survival during drought. This adaptive trait has been described as highly
      variable in a wide range of tree species, but little is known about the extent of
      genetic and phenotypic variability within species. This information is essential
      to our understanding of the evolutionary forces that have shaped this trait, and
      for evaluation of its inclusion in breeding programs. METHODOLOGY: We assessed
      cavitation resistance (P(50)), growth and carbon isotope composition in six Pinus
      pinaster populations in a provenance and progeny trial. We estimated the
      heritability of cavitation resistance and compared the distribution of neutral
      markers (F(ST)) and quantitative genetic differentiation (Q(ST)), for
      retrospective identification of the evolutionary forces acting on these traits.
      RESULTS/DISCUSSION: In contrast to growth and carbon isotope composition, no
      population differentiation was found for cavitation resistance. Heritability was
      higher than for the other traits, with a low additive genetic variance (h(2) (ns)
      = 0.43+/-0.18, CV(A) = 4.4%). Q(ST) was significantly lower than F(ST),
      indicating uniform selection for P(50), rather than genetic drift. Putative
      mechanisms underlying Q(ST)<F(ST) are discussed.

PMID- 21858138
TI  - Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a
      myth?
AB  - BACKGROUND: Brazil became the first developing country to guarantee free and
      universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being
      delivered to nearly 190,000 patients. The analysis of ARV price evolution and
      market dynamics in Brazil can help anticipate issues soon to afflict other
      developing countries, as the 2010 revision of the World Health Organization
      guidelines shifts demand towards more expensive treatments, and, at the same
      time, current evolution of international legislation and trade agreements on
      intellectual property rights may reduce availability of generic drugs for HIV
      care. METHODS AND FINDINGS: Our analyses are based on effective prices paid for
      ARV procurement in Brazil between 1996 and 2009. Data panel structure was
      exploited to gather ex-ante and ex-post information and address various sources
      of statistical bias. In-difference estimation offered in-depth information on ARV
      market characteristics which significantly influence prices. Although overall ARV
      prices follow a declining trend, changing characteristics in the generic segment
      help explain recent increase in generic ARV prices. Our results show that generic
      suppliers are more likely to respond to factors influencing demand size and
      market competition, while originator suppliers tend to set prices strategically
      to offset compulsory licensing threats and generic competition. SIGNIFICANCE: In
      order to guarantee the long term sustainability of access to antiretroviral
      treatment, our findings highlight the importance of preserving and stimulating
      generic market dynamics to sustain developing countries' bargaining power in
      price negotiations undertaken with originator companies.

PMID- 21858140
TI  - A novel multiplex real-time PCR for the identification of mycobacteria associated
      with zoonotic tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) is the leading cause of death worldwide from a
      single infectious agent. An ability to detect the Mycobacterium tuberculosis
      complex (MTC) in clinical material while simultaneously differentiating its
      members is considered important. This allows for the gathering of epidemiological
      information pertaining to the prevalence, transmission and geographical
      distribution of the MTC, including those MTC members associated with zoonotic TB
      infection in humans. Also differentiating between members of the MTC provides the
      clinician with inherent MTC specific drug susceptibility profiles to guide
      appropriate chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study
      was to develop a multiplex real-time PCR assay using novel molecular targets to
      identify and differentiate between the phylogenetically closely related M. bovis,
      M. bovis BCG and M. caprae. The lpqT gene was explored for the collective
      identification of M. bovis, M. bovis BCG and M. caprae, the lepA gene was
      targeted for the specific identification of M. caprae and a Region of Difference
      1 (RD1) assay was incorporated in the test to differentiate M. bovis BCG. The
      multiplex real-time PCR assay was evaluated on 133 bacterial strains and was
      determined to be 100% specific for the members of the MTC targeted.
      CONCLUSIONS/SIGNIFICANCE: The multiplex real-time PCR assay developed in this
      study is the first assay described for the identification and simultaneous
      differentiation of M. bovis, M. bovis BCG and M. caprae in one internally
      controlled reaction. Future validation of this multiplex assay should demonstrate
      its potential in the rapid and accurate diagnosis of TB caused by these three
      mycobacteria. Furthermore, the developed assay may be used in conjunction with a
      recently described multiplex real-time PCR assay for identification of the MTC
      and simultaneous differentiation of M. tuberculosis, M. canettii resulting in an
      ability to differentiate five of the eight members of the MTC.

PMID- 21858139
TI  - The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of
      ppGpp synthetases and hydrolases across the tree of life.
AB  - RelA/SpoT Homologue (RSH) proteins, named for their sequence similarity to the
      RelA and SpoT enzymes of Escherichia coli, comprise a superfamily of enzymes that
      synthesize and/or hydrolyze the alarmone ppGpp, activator of the "stringent"
      response and regulator of cellular metabolism. The classical "long" RSHs Rel,
      RelA and SpoT with the ppGpp hydrolase, synthetase, TGS and ACT domain
      architecture have been found across diverse bacteria and plant chloroplasts,
      while dedicated single domain ppGpp-synthesizing and -hydrolyzing RSHs have also
      been discovered in disparate bacteria and animals respectively. However, there is
      considerable confusion in terms of nomenclature and no comprehensive phylogenetic
      and sequence analyses have previously been carried out to classify RSHs on a
      genomic scale. We have performed high-throughput sensitive sequence searching of
      over 1000 genomes from across the tree of life, in combination with phylogenetic
      analyses to consolidate previous ad hoc identification of diverse RSHs in
      different organisms and provide a much-needed unifying terminology for the field.
      We classify RSHs into 30 subgroups comprising three groups: long RSHs, small
      alarmone synthetases (SASs), and small alarmone hydrolases (SAHs). Members of
      nineteen previously unidentified RSH subgroups can now be studied experimentally,
      including previously unknown RSHs in archaea, expanding the "stringent response"
      to this domain of life. We have analyzed possible combinations of RSH proteins
      and their domains in bacterial genomes and compared RSH content with available
      RSH knock-out data for various organisms to determine the rules of combining
      RSHs. Through comparative sequence analysis of long and small RSHs, we find
      exposed sites limited in conservation to the long RSHs that we propose are
      involved in transmitting regulatory signals. Such signals may be transmitted via
      NTD to CTD intra-molecular interactions, or inter-molecular interactions either
      among individual RSH molecules or among long RSHs and other binding partners such
      as the ribosome.

PMID- 21858141
TI  - AP-2delta is a crucial transcriptional regulator of the posterior midbrain.
AB  - Ap-2 transcription factors comprise a family of 5 closely related sequence
      specific DNA binding proteins that play pivotal and non-redundant roles in
      embryonic organogenesis. To investigate the function of Ap-2delta, wdeltae
      analyzed its expression during embryogenesis and generated Ap-2delta-deficient
      mice. In line with the specific expression pattern of Ap-2delta in the
      mesencephalic tectum and the dorsal midbrain, Ap-2delta-deficient mice failed to
      maintain the colliculus inferior, a derivative of the dorsal midbrain, as a
      consequence of increased apoptotic cell death. To identify specific Ap-2delta
      target genes in cells of the developing dorsal midbrain, we performed whole
      genome analysis of cDNA expression levels. This approach identified a set of 12
      putative target genes being expressed in the developing midbrain, including the
      transcription factors Pitx2, Mef2c, Bhlhb4 and Pou4f3. Using chromatin
      immunoprecipitation (CHIP) we showed that some of these genes are direct targets
      of Ap-2delta. Consistently, we demonstrate that Ap-2delta occupies and activates
      the Pou4f3 and Bhlhb4 promoters. In addition, known Pou4f3 target genes were
      downregulated in the posterior midbrain of Ap-2delta-deficient mice. Despite the
      absence of a central part of the auditory pathway, the presence of neuronal
      responses to sounds in the neocortex of Ap-2delta-deficient mice indicates that
      auditory information from the brainstem still reaches the neocortex. In summary,
      our data define Ap-2delta as an important transcription factor, specifying gene
      expression patterns required for the development of the posterior midbrain.

PMID- 21858142
TI  - To compare PubMed Clinical Queries and UpToDate in teaching information mastery
      to clinical residents: a crossover randomized controlled trial.
AB  - PURPOSE: To compare PubMed Clinical Queries and UpToDate regarding the amount and
      speed of information retrieval and users' satisfaction. METHOD: A cross-over
      randomized trial was conducted in February 2009 in Tehran University of Medical
      Sciences that included 44 year-one or two residents who participated in an
      information mastery workshop. A one-hour lecture on the principles of information
      mastery was organized followed by self learning slide shows before using each
      database. Subsequently, participants were randomly assigned to answer 2 clinical
      scenarios using either UpToDate or PubMed Clinical Queries then crossed to use
      the other database to answer 2 different clinical scenarios. The proportion of
      relevantly answered clinical scenarios, time to answer retrieval, and users'
      satisfaction were measured in each database. RESULTS: Based on intention-to-treat
      analysis, participants retrieved the answer of 67 (76%) questions using UpToDate
      and 38 (43%) questions using PubMed Clinical Queries (P<0.001). The median time
      to answer retrieval was 17 min (95% CI: 16 to 18) using UpToDate compared to 29
      min (95% CI: 26 to 32) using PubMed Clinical Queries (P<0.001). The satisfaction
      with the accuracy of retrieved answers, interaction with UpToDate and also
      overall satisfaction were higher among UpToDate users compared to PubMed Clinical
      Queries users (P<0.001). CONCLUSIONS: For first time users, using UpToDate
      compared to Pubmed Clinical Queries can lead to not only a higher proportion of
      relevant answer retrieval within a shorter time, but also a higher users'
      satisfaction. So, addition of tutoring pre-appraised sources such as UpToDate to
      the information mastery curricula seems to be highly efficient.

PMID- 21858143
TI  - ERK/MAPK is essential for endogenous neuroprotection in SCN2.2 cells.
AB  - BACKGROUND: Glutamate (Glu) is essential to central nervous system function;
      however excessive Glu release leads to neurodegenerative disease. Strategies to
      protect neurons are underdeveloped, in part due to a limited understanding of
      natural neuroprotective mechanisms, such as those present in the suprachiasmatic
      nucleus (SCN). This study tests the hypothesis that activation of ERK/MAPK
      provides essential protection to the SCN after exposure to excessive Glu using
      the SCN2.2 cells as a model. METHODOLOGY: Immortalized SCN2.2 cells (derived from
      SCN) and GT1-7 cells (neurons from the neighboring hypothalamus) were treated
      with 10 mM Glu in the presence or absence of the ERK/MAPK inhibitor PD98059. Cell
      death was assessed by Live/Dead assay, MTS assay and TUNEL. Caspase 3 activity
      was also measured. Activation of MAPK family members was determined by
      immunoblot. Bcl2, neuritin and Bid mRNA (by quantitative-PCR) and protein levels
      (by immunoblot) were also measured. PRINCIPAL FINDINGS: As expected Glu treatment
      increased caspase 3 activity and cell death in the GT1-7 cells, but Glu alone did
      not induce cell death or affect caspase 3 activity in the SCN2.2 cells. However,
      pretreatment with PD98059 increased caspase 3 activity and resulted in cell death
      after Glu treatment in SCN2.2 cells. This effect was dependent on NMDA receptor
      activation. Glu treatment in the SCN2.2 cells resulted in sustained activation of
      the anti-apoptotic pERK/MAPK, without affecting the pro-apoptotic p-p38/MAPK. In
      contrast, Glu exposure in GT1-7 cells caused an increase in p-p38/MAPK and a
      decrease in pERK/MAPK. Bcl2-protein increased in SCN2.2 cells following Glu
      treatment, but not in GT1-7 cells; bid mRNA and cleaved-Bid protein increased in
      GT1-7, but not SCN2.2 cells. CONCLUSIONS: Facilitation of ERK activation and
      inhibition of caspase activation promotes resistance to Glu excitotoxicity in
      SCN2.2 cells. SIGNIFICANCE: Further research will explore ERK/MAPK as a key
      molecule in the prevention of neurodegenerative processes.

PMID- 21858144
TI  - Isolation of genes involved in biofilm formation of a Klebsiella pneumoniae
      strain causing pyogenic liver abscess.
AB  - BACKGROUND: Community-acquired pyogenic liver abscess (PLA) complicated with
      meningitis and endophthalmitis caused by Klebsiella pneumoniae is an emerging
      infectious disease. To investigate the mechanisms and effects of biofilm
      formation of K. pneumoniae causing PLA, microtiter plate assays were used to
      determine the levels of biofilm formed by K. pneumoniae clinical isolates and to
      screen for biofilm-altered mutants from a transposon mutant library of a K.
      pneumoniae PLA-associated strain. METHODOLOGY/PRINCIPAL FINDINGS: The biofilm
      formation of K. pneumoniae was examined by microtiter plate assay. Higher levels
      of biofilm formation were demonstrated by K. pneumoniae strains associated with
      PLA. A total of 23 biofilm-decreased mutants and 4 biofilm-increased mutants were
      identified. Among these mutants, a biofilm-decreased treC mutant displayed less
      mucoviscosity and produced less capsular polysaccharide (CPS), whereas a biofilm
      increased sugE mutant displayed higher mucoviscosity and produced more CPS. The
      biofilm phenotypes of treC and sugE mutants also were confirmed by glass slide
      culture. Deletion of treC, which encodes trehalose-6-phosphate hydrolase,
      impaired bacterial trehalose utilization. Addition of glucose to the culture
      medium restored the capsule production and biofilm formation in the treC mutant.
      Transcriptional profile analysis suggested that the increase of CPS production in
      DeltasugE may reflect elevated cps gene expression (upregulated through rmpA) in
      combination with increased treC expression. In vivo competition assays
      demonstrated that the treC mutant strain was attenuated in competitiveness during
      intragastric infection in mice. CONCLUSIONS/SIGNIFICANCE: Genes important for
      biofilm formation by K. pneumoniae PLA strain were identified using an in vitro
      assay. Among the identified genes, treC and sugE affect biofilm formation by
      modulating CPS production. The importance of treC in gastrointestinal tract
      colonization suggests that biofilm formation contributes to the establishment and
      persistence of K. pneumoniae infection.

PMID- 21858145
TI  - Probing the role of protein surface charge in the activation of PrfA, the central
      regulator of Listeria monocytogenes pathogenesis.
AB  - Listeria monocytogenes is a food-borne intracellular bacterial pathogen capable
      of causing serious human disease. L. monocytogenes survival within mammalian
      cells depends upon the synthesis of a number of secreted virulence factors whose
      expression is regulated by the transcriptional activator PrfA. PrfA becomes
      activated following bacterial entry into host cells where it induces the
      expression of gene products required for bacterial spread to adjacent cells.
      Activation of PrfA appears to occur via the binding of a small molecule cofactor
      whose identity remains unknown. Electrostatic modeling of the predicted PrfA
      cofactor binding pocket revealed a highly positively charged region with two
      lysine residues, K64 and K122, located at the edge of the pocket and another
      (K130) located deep within the interior. Mutational analysis of these residues
      indicated that K64 and K122 contribute to intracellular activation of PrfA,
      whereas a K130 substitution abolished protein activity. The requirement of K64
      and K122 for intracellular PrfA activation could be bypassed via the introduction
      of the prfA G145S mutation that constitutively activates PrfA in the absence of
      cofactor binding. Our data indicate that the positive charge of the PrfA binding
      pocket contributes to intracellular activation of PrfA, presumably by
      facilitating binding of an anionic cofactor.

PMID- 21858146
TI  - NR-2L: a two-level predictor for identifying nuclear receptor subfamilies based
      on sequence-derived features.
AB  - Nuclear receptors (NRs) are one of the most abundant classes of transcriptional
      regulators in animals. They regulate diverse functions, such as homeostasis,
      reproduction, development and metabolism. Therefore, NRs are a very important
      target for drug development. Nuclear receptors form a superfamily of
      phylogenetically related proteins and have been subdivided into different
      subfamilies due to their domain diversity. In this study, a two-level predictor,
      called NR-2L, was developed that can be used to identify a query protein as a
      nuclear receptor or not based on its sequence information alone; if it is, the
      prediction will be automatically continued to further identify it among the
      following seven subfamilies: (1) thyroid hormone like (NR1), (2) HNF4-like (NR2),
      (3) estrogen like, (4) nerve growth factor IB-like (NR4), (5) fushi tarazu-F1
      like (NR5), (6) germ cell nuclear factor like (NR6), and (7) knirps like (NR0).
      The identification was made by the Fuzzy K nearest neighbor (FK-NN) classifier
      based on the pseudo amino acid composition formed by incorporating various
      physicochemical and statistical features derived from the protein sequences, such
      as amino acid composition, dipeptide composition, complexity factor, and low
      frequency Fourier spectrum components. As a demonstration, it was shown through
      some benchmark datasets derived from the NucleaRDB and UniProt with low
      redundancy that the overall success rates achieved by the jackknife test were
      about 93% and 89% in the first and second level, respectively. The high success
      rates indicate that the novel two-level predictor can be a useful vehicle for
      identifying NRs and their subfamilies. As a user-friendly web server, NR-2L is
      freely accessible at either http://icpr.jci.edu.cn/bioinfo/NR2L or http://www.jci
      bioinfo.cn/NR2L. Each job submitted to NR-2L can contain up to 500 query protein
      sequences and be finished in less than 2 minutes. The less the number of query
      proteins is, the shorter the time will usually be. All the program codes for NR
      2L are available for non-commercial purpose upon request.

PMID- 21858147
TI  - Transcriptional profiling of human liver identifies sex-biased genes associated
      with polygenic dyslipidemia and coronary artery disease.
AB  - Sex-differences in human liver gene expression were characterized on a genome
      wide scale using a large liver sample collection, allowing for detection of small
      expression differences with high statistical power. 1,249 sex-biased genes were
      identified, 70% showing higher expression in females. Chromosomal bias was
      apparent, with female-biased genes enriched on chrX and male-biased genes
      enriched on chrY and chr19, where 11 male-biased zinc-finger KRAB-repressor
      domain genes are distributed in six clusters. Top biological functions and
      diseases significantly enriched in sex-biased genes include transcription,
      chromatin organization and modification, sexual reproduction, lipid metabolism
      and cardiovascular disease. Notably, sex-biased genes are enriched at loci
      associated with polygenic dyslipidemia and coronary artery disease in genome-wide
      association studies. Moreover, of the 8 sex-biased genes at these loci, 4 have
      been directly linked to monogenic disorders of lipid metabolism and show an
      expression profile in females (elevated expression of ABCA1, APOA5 and LDLR;
      reduced expression of LIPC) that is consistent with the lower female risk of
      coronary artery disease. Female-biased expression was also observed for CYP7A1,
      which is activated by drugs used to treat hypercholesterolemia. Several sex
      biased drug-metabolizing enzyme genes were identified, including members of the
      CYP, UGT, GPX and ALDH families. Half of 879 mouse orthologs, including many
      genes of lipid metabolism and homeostasis, show growth hormone-regulated sex
      biased expression in mouse liver, suggesting growth hormone might play a similar
      regulatory role in human liver. Finally, the evolutionary rate of protein coding
      regions for human-mouse orthologs, revealed by dN/dS ratio, is significantly
      higher for genes showing the same sex-bias in both species than for non-sex
      biased genes. These findings establish that human hepatic sex differences are
      widespread and affect diverse cell metabolic processes, and may help explain sex
      differences in lipid profiles associated with sex differential risk of coronary
      artery disease.

PMID- 21858148
TI  - Molecular basis for the recognition of adenomatous polyposis coli by the Discs
      Large 1 protein.
AB  - The human Discs Large 1 (DLG1) protein uses two of its three PDZ domains to
      interact with the C-terminal peptide of the Adenomatous Polyposis Coli (APC)
      tumor suppressor protein. The DLG1/APC complex inhibits the cell cycle
      progression from the G0/G1 to the S phase, regulates epithelial cell migration
      and morphogenesis, and is required for polarization of the microtubule
      cytoskeleton. However, the molecular details of how DLG1 recognizes APC is not
      clear. In this study, we performed biochemical and biophysical assays to
      investigate the interactions between PDZ domains of DLG1 and the C-terminal
      peptide of APC. In addition, we determined the crystal structures of the PDZ1 and
      PDZ2 domains of DLG1 each in complex with the C-terminal 11-residue peptide of
      APC. Our biochemical, biophysical, and structural results revealed structural
      elements and residues on PDZ1 and PDZ2 domains of DLG1 and on APC crucial for
      their mutual interaction. In particular, our results show that the beta2/beta3
      loops of PDZ1 and PDZ2 play important roles in contributing to the binding
      affinities between PDZ domains and APC, through interacting with the residues
      upstream of the canonical PDZ-binding S/T-X-V motif. The results provide new
      insights into the binding mode of a defined C-terminal segment of APC by the PDZ
      domains of DLG1.

PMID- 21858149
TI  - Empirical evidence for son-killing X chromosomes and the operation of SA-zygotic
      drive.
AB  - BACKGROUND: Diploid organisms have two copies of all genes, but only one is
      carried by each haploid gamete and diploid offspring. This causes a fundamental
      genetic conflict over transmission rate between alternative alleles. Single
      genes, or gene clusters, only rarely code for the complex phenotypes needed to
      give them a transmission advantage (drive phenotype). However, all genes on a
      male's X and Y chromosomes co-segregate, allowing different sex-linked genes to
      code for different parts of the drive phenotype. Correspondingly, the well
      characterized phenomenon of male gametic drive, occurring during haploid
      gametogenesis, is especially common on sex chromosomes. The new theory of
      sexually antagonistic zygotic drive of the sex chromosomes (SA-zygotic drive)
      extends the logic of gametic drive into the diploid phase of the lifecycle,
      whenever there is competition among siblings or harmful sib-sib mating. The X and
      Y are predicted to gain a transmission advantage by harming offspring of the sex
      that does not carry them. RESULTS: Here we analyzed a mutant X-chromosome in
      Drosophila simulans that produced an excess of daughters when transmitted from
      males. We developed a series of tests to differentiate between gametic and SA
      zygotic drive, and provide multiple lines of evidence that SA-zygotic drive is
      responsible for the sex ratio bias. Driving sires produce about 50% more
      surviving daughters than sons. CONCLUSION: Sex-ratio distortion due to genetic
      conflict has evolved via gametic drive and maternally transmitted endosymbionts.
      Our data indicate that sex chromosomes can also drive by harming the non-carrier
      sex of offspring.

PMID- 21858150
TI  - High burden of non-influenza viruses in influenza-like illness in the early weeks
      of H1N1v epidemic in France.
AB  - BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens.
      Clinical observations are of little help to recognise myxovirus infection and
      implement appropriate prevention measures. The limited use of molecular tools
      underestimates the role of other common pathogens. OBJECTIVES: During the early
      weeks of the 2009-2010 flu pandemic, a clinical and virological survey was
      conducted in adult and paediatric patients with ILI referred to two French
      University hospitals in Paris and Tours. Aims were to investigate the different
      pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v
      pandemic influenza diagnosis was performed with real time RT-PCR assay. Other
      viral aetiologies were investigated by the molecular multiplex assay
      RespiFinder19(r). Clinical data were collected prospectively by physicians using
      a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were
      collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v.
      In 13 of them, other respiratory pathogens were also detected. Among H1N1v
      negative samples, 213 (61.9%) were positive for various respiratory agents, 190
      in single infections and 23 in mixed infections. The most prevalent viruses in
      H1N1v negative single infections were rhinovirus (62.6%), followed by
      parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were
      identified in patients under 40 years and none after 65 years. There was no
      difference between clinical symptoms observed in patients infected with H1N1v or
      with other pathogens. CONCLUSION: Our results highlight the high frequency of non
      influenza viruses involved in ILI during the pre-epidemic period of a flu alert
      and the lack of specific clinical signs associated with influenza infections.
      Rapid diagnostic screening of a large panel of respiratory pathogens may be
      critical to define and survey the epidemic situation and to provide critical
      information for patient management.

PMID- 21858151
TI  - Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by
      Chk1 inactivation.
AB  - The DNA-damage checkpoint kinase Chk1 is essential in higher eukaryotes due to
      its role in maintaining genome stability in proliferating cells. CHK1 gene
      deletion is embryonically lethal, and Chk1 inhibition in replicating cells causes
      cell-cycle defects that eventually lead to perturbed replication and replication
      fork collapse, thus generating endogenous DNA damage. What is the cause of
      replication-fork collapse when Chk1 is inactivated, however, remains poorly
      understood. Here, we show that generation of DNA double-strand breaks at
      replication forks when Chk1 activity is compromised relies on the DNA
      endonuclease complex Mus81/Eme1. Importantly, we show that Mus81/Eme1-dependent
      DNA damage--rather than a global increase in replication-fork stalling--is the
      cause of incomplete replication in Chk1-deficient cells. Consequently, Mus81/Eme1
      depletion alleviates the S-phase progression defects associated with Chk1
      deficiency, thereby increasing cell survival. Chk1-mediated protection of
      replication forks from Mus81/Eme1 even under otherwise unchallenged conditions is
      therefore vital to prevent uncontrolled fork collapse and ensure proper S-phase
      progression in human cells.

PMID- 21858152
TI  - The glycan shield of HIV is predominantly oligomannose independently of
      production system or viral clade.
AB  - The N-linked oligomannose glycans of HIV gp120 are a target for both microbicide
      and vaccine design. The extent of cross-clade conservation of HIV oligomannose
      glycans is therefore a critical consideration for the development of HIV
      prophylaxes. We measured the oligomannose content of virion-associated gp120 from
      primary virus from PBMCs for a range of viral isolates and showed cross-clade
      elevation (62-79%) of these glycans relative to recombinant, monomeric gp120
      (~30%). We also confirmed that pseudoviral production systems can give rise to
      notably elevated gp120 oligomannose levels (~98%), compared to gp120 derived from
      a single-plasmid viral system using the HIV(LAI) backbone (56%). This study
      highlights differences in glycosylation between virion-associated and recombinant
      gp120.

PMID- 21858153
TI  - Activation of aryl hydrocarbon receptor (AhR) leads to reciprocal epigenetic
      regulation of FoxP3 and IL-17 expression and amelioration of experimental
      colitis.
AB  - BACKGROUND: Aryl hydrocarbon receptor (AhR), a transcription factor of the
      bHLH/PAS family, is well characterized to regulate the biochemical and toxic
      effects of environmental chemicals. More recently, AhR activation has been shown
      to regulate the differentiation of Foxp3(+) Tregs as well as Th17 cells. However,
      the precise mechanisms are unclear. In the current study, we investigated the
      effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on
      epigenetic regulation leading to altered Treg/Th17 differentiation, and
      consequent suppression of colitis. METHODOLOGY/PRINCIPAL FINDINGS: Dextran sodium
      sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by
      significant weight loss, shortening of colon, mucosal ulceration, and increased
      presence of CXCR3(+) T cells as well as inflammatory cytokines. Interestingly, a
      single dose of TCDD (25 ug/kg body weight) was able to attenuate all of the
      clinical and inflammatory markers of colitis. Analysis of T cells in the lamina
      propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased
      presence of Tregs and increased induction of Th17 cells, which was reversed
      following TCDD treatment. Activation of T cells from AhR(+/+) but not AhR (-/-)
      mice, in the presence of TCDD, promoted increased differentiation of Tregs while
      inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed
      increased methylation of CpG islands of Foxp3 and demethylation of IL-17
      promoters, which was reversed following TCDD treatment. CONCLUSIONS/SIGNIFICANCE:
      These studies demonstrate for the first time that AhR activation promotes
      epigenetic regulation thereby influencing reciprocal differentiation of Tregs and
      Th17 cells, and amelioration of inflammation.

PMID- 21858154
TI  - Vitamin D receptor deficiency enhances Wnt/beta-catenin signaling and tumor
      burden in colon cancer.
AB  - Aberrant activation of the Wnt/beta-catenin pathway is critical for the
      initiation and progression of most colon cancers. This activation provokes the
      accumulation of nuclear beta-catenin and the induction of its target genes.
      Apc(min/+) mice are the most commonly used model for colon cancer. They harbor a
      mutated Apc allele and develop intestinal adenomas and carcinomas during the
      first months of life. This phenotype is caused by the mutation of the second Apc
      allele and the consequent accumulation of nuclear beta-catenin in the affected
      cells. Here we describe that vitamin D receptor (VDR) is a crucial modulator of
      nuclear beta-catenin levels in colon cancer in vivo. By appropriate breeding of
      Apc(min/+) mice and Vdr(+/-) mice we have generated animals expressing a mutated
      Apc allele and two, one, or none Vdr wild type alleles. Lack of Vdr increased the
      number of colonic Aberrant Crypt Foci (ACF) but not that of adenomas or
      carcinomas in either small intestine or colon. Importantly, colon ACF and tumors
      of Apc(min/+)Vdr(-/-) mice had increased nuclear beta-catenin and the tumors
      reached a larger size than those of Apc(min/+)Vdr(+/+). Both ACF and carcinomas
      in Apc(min/+)Vdr(-/-) mice showed higher expression of beta-catenin/TCF target
      genes. In line with this, VDR knock-down in cultured human colon cancer cells
      enhanced beta-catenin nuclear content and target gene expression. Consistently,
      VDR depletion abrogated the capacity of 1,25(OH)(2)D(3) to promote the relocation
      of beta-catenin from the nucleus to the plasma membrane and to inhibit beta
      catenin/TCF target genes. In conclusion, VDR controls the level of nuclear beta
      catenin in colon cancer cells and can therefore attenuate the impact of oncogenic
      mutations that activate the Wnt/beta-catenin pathway.

PMID- 21858155
TI  - OASIS: online application for the survival analysis of lifespan assays performed
      in aging research.
AB  - BACKGROUND: Aging is a fundamental biological process. Characterization of
      genetic and environmental factors that influence lifespan is a crucial step
      toward understanding the mechanisms of aging at the organism level. To capture
      the different effects of genetic and environmental factors on lifespan,
      appropriate statistical analyses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We
      developed an online application for survival analysis (OASIS) that helps conduct
      various novel statistical tasks involved in analyzing survival data in a user
      friendly manner. OASIS provides standard survival analysis results including
      Kaplan-Meier estimates and mean/median survival time by taking censored survival
      data. OASIS also provides various statistical tests including comparison of mean
      survival time, overall survival curve, and survival rate at specific time point.
      To visualize survival data, OASIS generates survival and log cumulative hazard
      plots that enable researchers to easily interpret their experimental results.
      Furthermore, we provide statistical methods that can analyze variances among
      survival datasets. In addition, users can analyze proportional effects of risk
      factors on survival. CONCLUSIONS/SIGNIFICANCE: OASIS provides a platform that is
      essential to facilitate efficient statistical analyses of survival data in the
      field of aging research. Web application and a detailed description of algorithms
      are accessible from http://sbi.postech.ac.kr/oasis.

PMID- 21858156
TI  - Lifespan-extending effects of royal jelly and its related substances on the
      nematode Caenorhabditis elegans.
AB  - BACKGROUND: One of the most important challenges in the study of aging is to
      discover compounds with longevity-promoting activities and to unravel their
      underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse
      beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional
      pharmacological activities. Exactly how RJ and pRJ exert these effects and which
      of their components are responsible for these effects are largely unknown. The
      evolutionarily conserved mechanisms that control longevity have been indicated.
      The purpose of the present study was to determine whether RJ and its related
      substances exert a lifespan-extending function in the nematode Caenorhabditis
      elegans and to gain insights into the active agents in RJ and their mechanism of
      action. PRINCIPAL FINDINGS: We found that both RJ and pRJ extended the lifespan
      of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl
      silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals'
      lifespan in part by acting through the FOXO transcription factor DAF-16, the
      activation of which is known to promote longevity in C. elegans by reducing
      insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of
      the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some
      common features in terms of their effects on gene expression, such as the up
      regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10
      Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ
      Fr.5, increased lifespan independently of DAF-16 activity.
      CONCLUSIONS/SIGNIFICANCE: These results demonstrate that RJ and its related
      substances extend lifespan in C. elegans, suggesting that RJ may contain
      longevity-promoting factors. Further analysis and characterization of the
      lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene
      network involved in longevity regulation in diverse species and may lead to the
      development of nutraceutical interventions in the aging process.

PMID- 21858157
TI  - A reassessment of carbon content in tropical trees.
AB  - Accurate knowledge of carbon (C) content in live wood is essential for
      quantifying tropical forest C stocks, yet generic assumptions (such as biomass
      consisting of 50% carbon on a weight/weight basis) remain widely used despite
      being supported by little chemical analysis. Empirical data from stem cores of 59
      Panamanian rainforest tree species demonstrate that wood C content is highly
      variable among co-occurring species, with an average (47.4+/-2.51% S.D.)
      significantly lower than widely assumed values. Prior published values have
      neglected to account for volatile C content of tropical woods. By comparing
      freeze- and oven-dried wood samples, we show that volatile C is non-negligible,
      and excluding the volatile fraction underestimates wood C content by 2.48+/-1.28%
      (S.D.) on average. Wood C content varied substantially among species (from 41.9
      51.6%), but was neither strongly phylogenetically conserved, nor correlated to
      ecological (i.e. wood density, maximum tree height) or demographic traits (i.e.
      relative growth rate, mortality rate). Overall, assuming generic C fractions in
      tropical wood overestimates forest C stocks by ~3.3-5.3%, a non-trivial margin of
      error leading to overestimates of 4.1-6.8 Mg C ha(-1) in a 50-ha forest dynamics
      plot on Barro Colorado Island, Panama. In addition to addressing other sources of
      error in tropical forest C accounting, such as uncertainties in allometric models
      and belowground biomass, compilation and use of species-specific C fractions for
      tropical tree species would substantially improve both local and global estimates
      of terrestrial C stocks and fluxes.

PMID- 21858158
TI  - A gain-of-function germline mutation in Drosophila ras1 affects apoptosis and
      cell fate during development.
AB  - The RAS/MAPK signal transduction pathway is an intracellular signaling cascade
      that transmits environmental signals from activated receptor tyrosine kinases
      (RTKs) on the cell surface and other endomembranes to transcription factors in
      the nucleus, thereby linking extracellular stimuli to changes in gene expression.
      Largely as a consequence of its role in oncogenesis, RAS signaling has been the
      subject of intense research efforts for many years. More recently, it has been
      shown that milder perturbations in Ras signaling during embryogenesis also
      contribute to the etiology of a group of human diseases. Here we report the
      identification and characterization of the first gain-of-function germline
      mutation in Drosophila ras1 (ras85D), the Drosophila homolog of human K-ras, N
      ras and H-ras. A single amino acid substitution (R68Q) in the highly conserved
      switch II region of Ras causes a defective protein with reduced intrinsic GTPase
      activity, but with normal sensitivity to GAP stimulation. The ras1(R68Q) mutant
      is homozygous viable but causes various developmental defects associated with
      elevated Ras signaling, including cell fate changes and ectopic survival of cells
      in the nervous system. These biochemical and functional properties are
      reminiscent of germline Ras mutants found in patients afflicted with Noonan,
      Costello or cardio-facio-cutaneous syndromes. Finally, we used ras1(R68Q) to
      identify novel genes that interact with Ras and suppress cell death.

PMID- 21858159
TI  - Role of reuniens nucleus projections to the medial prefrontal cortex and to the
      hippocampal pyramidal CA1 area in associative learning.
AB  - We studied the interactions between short- and long-term plastic changes taking
      place during the acquisition of a classical eyeblink conditioning and following
      high-frequency stimulation (HFS) of the reuniens nucleus in behaving mice.
      Synaptic changes in strength were studied at the reuniens-medial prefrontal
      cortex (mPFC) and the reuniens-CA1 synapses. Input/output curves and a paired
      pulse study enabled determining the functional capabilities of the two synapses
      and the optimal intensities to be applied at the reuniens nucleus during
      classical eyeblink conditioning and for HFS applied to the reuniens nucleus.
      Animals were conditioned using a trace paradigm, with a tone as conditioned
      stimulus (CS) and an electric shock to the trigeminal nerve as unconditioned
      stimulus (US). A single pulse was presented to the reuniens nucleus to evoke
      field EPSPs (fEPSPs) in mPFC and CA1 areas during the CS-US interval. No
      significant changes in synaptic strength were observed at the reuniens-mPFC and
      reuniens-CA1 synapses during the acquisition of eyelid conditioned responses
      (CRs). Two successive HFS sessions carried out during the first two conditioning
      days decreased the percentage of CRs, without evoking any long-term potentiation
      (LTP) at the recording sites. HFS of the reuniens nucleus also prevented the
      proper acquisition of an object discrimination task. A subsequent study revealed
      that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse
      facilitation. In conclusion, reuniens nucleus projections to prefrontal and
      hippocampal circuits seem to participate in the acquisition of associative
      learning through a mechanism that does not required the development of LTP.

PMID- 21858160
TI  - Toll-like receptor 4 is involved in inflammatory and joint destructive pathways
      in collagen-induced arthritis in DBA1J mice.
AB  - In rheumatoid arthritis, a significant proportion of cytokine and chemokine
      synthesis is attributed to innate immune mechanisms. TLR4 is a prominent innate
      receptor since several endogenous ligands known to activate the innate immune
      system bind to it and may thereby promote joint inflammation. We generated TLR4
      deficient DBA1J mice by backcrossing the TLR4 mutation present in C3H/HeJ strain
      onto the DBA1J strain and investigated the course of collagen-induced arthritis
      in TLR4 deficient mice in comparison to wild type littermates. The incidence of
      collagen- induced arthritis was significantly lower in TLR4 deficient compared to
      wild type mice (59 percent vs. 100 percent). The severity of arthritis was
      reduced in the TLR4 deficient mice compared to wild type littermates (mean
      maximum score 2,54 vs. 6,25). Mice deficient for TLR4 were virtually protected
      from cartilage destruction, and infiltration of inflammatory cells was reduced
      compared to wt mice. In parallel to the decreased clinical severity, lower anti
      CCP antibody concentrations and lower IL-17 concentrations were found in the TLR4
      deficient mice. The study further supports the role of TLR4 in the propagation of
      joint inflammation and destruction. Moreover, since deficiency in TLR4 led to
      decreased IL-17 and anti-CCP antibody production, the results indicate a link
      between TLR4 stimulation and the adaptive autoimmune response. This mechanism
      might be relevant in human rheumatoid arthritis, possibly in response to
      activating endogenous ligands in the affected joints.

PMID- 21858161
TI  - Toll-like receptor 2 induced angiogenesis and invasion is mediated through the
      Tie2 signalling pathway in rheumatoid arthritis.
AB  - BACKGROUND: Angiogenesis is a critical early event in inflammatory arthritis,
      facilitating leukocyte migration into the synovium resulting in invasion and
      destruction of articular cartilage and bone. This study investigates the effect
      of TLR2 on angiogenesis, EC adhesion and invasion using microvascular endothelial
      cells and RA whole tissue synovial explants ex-vivo. METHODS: Microvascular
      endothelial cells (HMVEC) and RA synovial explants ex vivo were cultured with the
      TLR2 ligand, Pam3CSK4 (1 ug/ml). Angiopoietin 2 (Ang2), Tie2 and TLR2 expression
      in RA synovial tissue was assessed by immunohistology. HMVEC tube formation was
      assessed using Matrigel matrix assays. Ang2 was measured by ELISA. ICAM-1 cell
      surface expression was assessed by flow cytometry. Cell migration was assessed by
      wound repair scratch assays. ECM invasion, MMP-2 and -9 expression were assessed
      using transwell invasion chambers and zymography. To examine if the
      angiopoietin/Tie2 signalling pathway mediates TLR2 induced EC tube formation,
      invasion and migration assays were performed in the presence of a specific
      neutralising anti-Tie2mAb (10 ug/ml) and matched IgG isotype control Ab (10
      ug/ml). RESULTS: Ang2 and Tie2 were localised to RA synovial blood vessels, and
      TLR2 was localised to RA synovial blood vessels, sub-lining infiltrates and the
      lining layer. Pam3CSK4 significantly increased angiogenic tube formation
      (p<0.05), and upregulated Ang2 production in HMVEC (p<0.05) and RA synovial
      explants (p<0.05). Pam3CSK4 induced cell surface expression of ICAM-1, from basal
      level of 149+/-54 (MFI) to 617+/-103 (p<0.01). TLR-2 activation induced an 8.8+/
      2.8 fold increase in cell invasion compared to control (p<0.05). Pam3CSK4 also
      induced HMVEC cell migration and induced MMP-2 and -9 from RA synovial explants.
      Neutralisation of the Ang2 receptor, Tie2 significantly inhibited Pam3CSK4
      induced EC tube formation and invasion (p<0.05). CONCLUSION: TLR2 activation
      promotes angiogenesis, cell adhesion and invasion, effects that are in part
      mediated through the Tie2 signalling pathway, key mechanisms involved in the
      pathogenesis of RA.

PMID- 21858162
TI  - Selective genomic copy number imbalances and probability of recurrence in early
      stage breast cancer.
AB  - A number of studies of copy number imbalances (CNIs) in breast tumors support
      associations between individual CNIs and patient outcomes. However, no pattern or
      signature of CNIs has emerged for clinical use. We determined copy number (CN)
      gains and losses using high-density molecular inversion probe (MIP) arrays for
      971 stage I/II breast tumors and applied a boosting strategy to fit hazards
      models for CN and recurrence, treating chromosomal segments in a dose-specific
      fashion (-1 [loss], 0 [no change] and +1 [gain]). The concordance index (C-Index)
      was used to compare prognostic accuracy between a training (n = 728) and test (n
      = 243) set and across models. Twelve novel prognostic CNIs were identified:
      losses at 1p12, 12q13.13, 13q12.3, 22q11, and Xp21, and gains at 2p11.1, 3q13.12,
      10p11.21, 10q23.1, 11p15, 14q13.2-q13.3, and 17q21.33. In addition, seven CNIs
      previously implicated as prognostic markers were selected: losses at 8p22 and
      16p11.2 and gains at 10p13, 11q13.5, 12p13, 20q13, and Xq28. For all breast
      cancers combined, the final full model including 19 CNIs, clinical covariates,
      and tumor marker-approximated subtypes (estrogen receptor [ER], progesterone
      receptor, ERBB2 amplification, and Ki67) significantly outperformed a model
      containing only clinical covariates and tumor subtypes (C-Index(full model),
      train[test]  =  0.72[0.71] +/- 0.02 vs. C-Index(clinical + subtype model),
      train[test]  =  0.62[0.62] +/- 0.02; p<10(-6)). In addition, the full model
      containing 19 CNIs significantly improved prognostication separately for ER-,
      HER2+, luminal B, and triple negative tumors over clinical variables alone. In
      summary, we show that a set of 19 CNIs discriminates risk of recurrence among
      early-stage breast tumors, independent of ER status. Further, our data suggest
      the presence of specific CNIs that promote and, in some cases, limit tumor
      spread.

PMID- 21858163
TI  - Non-detection of human herpesvirus 8 (HHV-8) DNA in HHV-8-seropositive blood
      donors from three Brazilian regions.
AB  - Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated
      herpesvirus (KSHV), is the etiologic agent of all forms of Kaposi's sarcoma,
      primary effusion lymphoma and the plasmablastic cell variant of multicentric
      Castleman disease. In endemic areas of sub-Saharan Africa, blood transfusions
      have been associated with a substantial risk of HHV-8 transmission. By contrast,
      several studies among healthy blood donors from North America have failed to
      detect HHV-8 DNA in samples of seropositive individuals. In this study, using a
      real-time PCR assay, we investigated the presence of HHV-8 DNA in whole-blood
      samples of 803 HHV-8 blood donors from three Brazilian states (Sao Paulo, Amazon,
      Bahia) who tested positive for HHV-8 antibodies, in a previous multicenter study.
      HHV-8 DNA was not detected in any sample. Our findings do not support the
      introduction of routine HHV-8 screening among healthy blood donors in Brazil. (WC
      = 140).

PMID- 21858164
TI  - Condensin I recruitment to base damage-enriched DNA lesions is modulated by
      PARP1.
AB  - Condensin I is important for chromosome organization and segregation in mitosis.
      We previously showed that condensin I also interacts with PARP1 in response to
      DNA damage and plays a role in single-strand break repair. However, whether
      condensin I physically associates with DNA damage sites and how PARP1 may
      contribute to this process were unclear. We found that condensin I is
      preferentially recruited to DNA damage sites enriched for base damage. This
      process is dictated by PARP1 through its interaction with the chromosome
      targeting domain of the hCAP-D2 subunit of condensin I.

PMID- 21858165
TI  - Characterization and comparative profiling of MiRNA transcriptomes in bighead
      carp and silver carp.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that are processed from
      large 'hairpin' precursors and function as post-transcriptional regulators of
      target genes. Although many individual miRNAs have recently been extensively
      studied, there has been very little research on miRNA transcriptomes in teleost
      fishes. By using high throughput sequencing technology, we have identified 167
      and 166 conserved miRNAs (belonging to 108 families) in bighead carp
      (Hypophthalmichthys nobilis) and silver carp (Hypophthalmichthys molitrix),
      respectively. We compared the expression patterns of conserved miRNAs by means of
      hierarchical clustering analysis and log2 ratio. Results indicated that there is
      not a strong correlation between sequence conservation and expression
      conservation, most of these miRNAs have similar expression patterns. However,
      high expression differences were also identified for several individual miRNAs.
      Several miRNA* sequences were also found in our dataset and some of them may have
      regulatory functions. Two computational strategies were used to identify novel
      miRNAs from un-annotated data in the two carps. A first strategy based on
      zebrafish genome, identified 8 and 22 novel miRNAs in bighead carp and silver
      carp, respectively. We postulate that these miRNAs should also exist in the
      zebrafish, but the methodologies used have not allowed for their detection. In
      the second strategy we obtained several carp-specific miRNAs, 31 in bighead carp
      and 32 in silver carp, which showed low expression. Gain and loss of family
      members were observed in several miRNA families, which suggests that duplication
      of animal miRNA genes may occur through evolutionary processes which are similar
      to the protein-coding genes.

PMID- 21858166
TI  - A higher correlation of HCV core antigen with CD4+ T cell counts compared with
      HCV RNA in HCV/HIV-1 coinfected patients.
AB  - Development of HCV infection is typically followed by chronic hepatitis C (CHC)
      in most patients, while spontaneous HCV viral clearance (SVC) occurs in only a
      minority of subjects. Compared with the widespread application of HCV RNA testing
      by quantitative RT-PCR technique, HCV core antigen detection may be an
      alternative indicator in the diagnosis of hepatitis C virus infections and in
      monitoring the status of infectious individuals. However, the correlation and
      differences between these two indicators in HCV infection need more
      investigation, especially in patients coinfected by HIV-1. In this study, a total
      of 354 anti-HCV and/or anti-HIV serum positive residents from a village of
      central China were enrolled. Besides HCV-related hepatopathic variables including
      clinical status, ALT, AST, anti-HCV Abs, as well as the altered CD4+/CD8+ T cell
      counts, HCV core antigen and HCV viral load were also measured. The concentration
      of serum HCV core antigen was highly correlated with level of HCV RNA in CHC
      patients with or without HIV-1 coinfection. Of note, HCV core antigen
      concentration was negatively correlated with CD4+ T cell count, while no
      correlation was found between HCV RNA level and CD4+ T cell count. Our findings
      suggested that quantitative detection of plasma HCV core antigen may be an
      alternative indicator of HCV RNA qPCR assay when evaluating the association
      between HCV replication and host immune status in HCV/HIV-1 coinfected patients.

PMID- 21858168
TI  - Boldness predicts social status in zebrafish (Danio rerio).
AB  - This study explored if boldness could be used to predict social status. First,
      boldness was assessed by monitoring individual zebrafish behaviour in (1) an
      unfamiliar barren environment with no shelter (open field), (2) the same
      environment when a roof was introduced as a shelter, and (3) when the roof was
      removed and an unfamiliar object (Lego(r) brick) was introduced. Next, after a
      resting period of minimum one week, social status of the fish was determined in a
      dyadic contest and dominant/subordinate individuals were determined as the
      winner/loser of two consecutive contests. Multivariate data analyses showed that
      males were bolder than females and that the behaviours expressed by the fish
      during the boldness tests could be used to predict which fish would later become
      dominant and subordinate in the ensuing dyadic contest. We conclude that bold
      behaviour is positively correlated to dominance in zebrafish and that boldness is
      not solely a consequence of social dominance.

PMID- 21858167
TI  - Rapid probing of biological surfaces with a sparse-matrix peptide library.
AB  - Finding unique peptides to target specific biological surfaces is crucial to
      basic research and technology development, though methods based on biological
      arrays or large libraries limit the speed and ease with which these necessary
      compounds can be found. We reasoned that because biological surfaces, such as
      cell surfaces, mineralized tissues, and various extracellular matrices have
      unique molecular compositions, they present unique physicochemical signatures to
      the surrounding medium which could be probed by peptides with appropriately
      corresponding physicochemical properties. To test this hypothesis, a naive pilot
      library of 36 peptides, varying in their hydrophobicity and charge, was arranged
      in a two-dimensional matrix and screened against various biological surfaces.
      While the number of peptides in the matrix library was very small, we obtained
      "hits" against all biological surfaces probed. Sequence refinement of the "hits"
      led to peptides with markedly higher specificity and binding activity against
      screened biological surfaces. Genetic studies revealed that peptide binding to
      bacteria was mediated, at least in some cases, by specific cell-surface
      molecules, while examination of human tooth sections showed that this method can
      be used to derive peptides with highly specific binding to human tissue.

PMID- 21858169
TI  - Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes
      in diabetes mellitus.
AB  - The number of kidney podocytes is reduced in diabetic nephropathy. Advanced
      glycation end products (AGEs) accumulate in patients with diabetes and promote
      the apoptosis of podocyte by activating the forkhead box O4 (Foxo4) transcription
      factor to increase the expression of a pro-apoptosis gene, Bcl2l11. Using
      chromatin immunoprecipitation we demonstrate that AGE-modified bovine serum
      albumin (AGE-BSA) enhances Foxo4 binding to a forkhead binding element in the
      promoter of Bcl2lll. AGE-BSA also increases the acetylation of Foxo4. Lysine
      acetylation of Foxo4 is required for Foxo4 binding and transcription of Bcl2l11
      in podocytes treated with AGE-BSA. The expression of a protein deacetylase that
      targets Foxo4 for deacetylation, sirtuin (Sirt1), is down regulated in cultured
      podocytes by AGE-BSA treatment and in glomeruli of diabetic patients. SIRT1 over
      expression in cultured murine podocytes prevents AGE-induced apoptosis. Glomeruli
      isolated from diabetic db/db mice have increased acetylation of Foxo4, suppressed
      expression of Sirt1, and increased expression of Bcl2l11 compared to non-diabetic
      littermates. Together, our data provide evidence that alteration of Foxo4
      acetylation and down regulation of Sirt1 expression in diabetes promote podocyte
      apoptosis. Strategies to preserve Sirt1 expression or reduce Foxo4 acetylation
      could be used to prevent podocyte loss in diabetes.

PMID- 21858170
TI  - The distribution of phosphatidylinositol 4,5-bisphosphate in acinar cells of rat
      pancreas revealed with the freeze-fracture replica labeling method.
AB  - Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] is a phospholipid that has
      been implicated in multiple cellular activities. The distribution of PI(4,5)P(2)
      has been analyzed extensively using live imaging of the GFP-coupled phospholipase
      C-delta1 pleckstrin homology domain in cultured cell lines. However, technical
      difficulties have prevented the study of PI(4,5)P(2) in cells of in vivo tissues.
      We recently developed a method to analyze the nanoscale distribution of
      PI(4,5)P(2) in cultured cells by using the quick-freezing and freeze-fracture
      replica labeling method. In principle, this method can be applied to any cell
      because it does not require the expression of artificial probes. In the present
      study, we modified the method to study cells of in vivo tissues and applied it to
      pancreatic exocrine acinar cells of the rat. We found that PI(4,5)P(2) in the
      plasma membrane is distributed in an equivalent density in the apical and
      basolateral domains, but exists in a significantly higher concentration in the
      gap junction. The intracellular organelles did not show labeling for PI(4,5)P(2).
      The results are novel or different from the reported distribution patterns in
      cell lines and highlight the importance of studying cells differentiated in vivo.

PMID- 21858171
TI  - Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by
      p21 in mesothelioma.
AB  - BACKGROUND: Malignant mesothelioma (MM) is a rare, highly aggressive tumor,
      associated to asbestos exposure. To date no chemotherapy regimen for MM has
      proven to be definitively curative, and new therapies for MM treatment need to be
      developed. We have previously shown in vivo that piroxicam/cisplatin combined
      treatment in MM, specifically acts on cell cycle regulation triggering apoptosis,
      with survival increase. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed, at molecular
      level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell
      lines. By means of genome wide analyses, we analyzed transcriptional gene
      deregulation both after the single piroxicam or cisplatin and the combined
      treatment. Here we show that apoptotic increase following combined treatment is
      mediated by p21, since apoptotic increase in piroxicam/cisplatin combined
      treatment is abolished upon p21 silencing. CONCLUSIONS/SIGNIFICANCE:
      Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM
      cells, which is dependent on the p21 expression. The results provided suggest
      that piroxicam/cisplatin combination might be tested in clinical settings in
      tumor specimens that express p21.

PMID- 21858172
TI  - Probing the interaction of the diarylquinoline TMC207 with its target
      mycobacterial ATP synthase.
AB  - Infections with Mycobacterium tuberculosis are substantially increasing on a
      worldwide scale and new antibiotics are urgently needed to combat concomitantly
      emerging drug-resistant mycobacterial strains. The diarylquinoline TMC207 is a
      highly promising drug candidate for treatment of tuberculosis. This compound
      kills M. tuberculosis by binding to a new target, mycobacterial ATP synthase. In
      this study we used biochemical assays and binding studies to characterize the
      interaction between TMC207 and ATP synthase. We show that TMC207 acts independent
      of the proton motive force and does not compete with protons for a common binding
      site. The drug is active on mycobacterial ATP synthesis at neutral and acidic pH
      with no significant change in affinity between pH 5.25 and pH 7.5, indicating
      that the protonated form of TMC207 is the active drug entity. The interaction of
      TMC207 with ATP synthase can be explained by a one-site binding mechanism, the
      drug molecule thus binds to a defined binding site on ATP synthase. TMC207
      affinity for its target decreases with increasing ionic strength, suggesting that
      electrostatic forces play a significant role in drug binding. Our results are
      consistent with previous docking studies and provide experimental support for a
      predicted function of TMC207 in mimicking key residues in the proton transfer
      chain and blocking rotary movement of subunit c during catalysis. Furthermore,
      the high affinity of TMC207 at low proton motive force and low pH values may in
      part explain the exceptional ability of this compound to efficiently kill
      mycobacteria in different microenvironments.

PMID- 21858173
TI  - Characteristics of suicide attempts in anorexia and bulimia nervosa: a case
      control study.
AB  - OBJECTIVE: Compared to other eating disorders, anorexia nervosa (AN) has the
      highest rates of completed suicide whereas suicide attempt rates are similar or
      lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of
      suicide, thus this mismatch is intriguing. We sought to explore whether the
      clinical characteristics of suicidal acts differ between suicide attempters with
      AN, BN or without an eating disorders (ED). METHOD: Case-control study in a
      cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with
      BN were compared with 235 non-ED attempters matched for sex, age and education,
      using interview measures of suicidal intent and severity. RESULTS: AN patients
      were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4-7.9), with
      a higher expectation of dying (OR = 3.7,95% CI 1.1-13.5), and an increased risk
      of severity (OR = 3.4,95% CI 1.2-9.6). BN patients did not differ from the
      control group. Clinical markers of the severity of ED were associated with the
      seriousness of the attempt. CONCLUSION: There are distinct features of suicide
      attempts in AN. This may explain the higher suicide rates in AN. Higher completed
      suicide rates in AN may be partially explained by AN patients' higher desire to
      die and their more severe and lethal attempts.

PMID- 21858174
TI  - Eukaryotic cells producing ribosomes deficient in Rpl1 are hypersensitive to
      defects in the ubiquitin-proteasome system.
AB  - It has recently become clear that the misassembly of ribosomes in eukaryotic
      cells can have deleterious effects that go far beyond a simple shortage of
      ribosomes. In this work we find that cells deficient in ribosomal protein L1
      (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the
      cytoplasm and that can be incorporated into polyribosomes. The presence of such
      defective ribosomes leads to slow growth and appears to render the cells
      hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that
      were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to
      do so, suggesting that key players in the surveillance of ribosomal subunits
      remain to be found. Interestingly, in spite of rendering the cells hypersensitive
      to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the
      stress-invoked temporary repression of ribosome synthesis caused by MG132.

PMID- 21858175
TI  - Real-time PCR-based analysis of the human bile microRNAome identifies miR-9 as a
      potential diagnostic biomarker for biliary tract cancer.
AB  - Biliary tract cancer (BTC) is often difficult to diagnose definitively, even
      through histological examination. MicroRNAs (miRNAs) regulate a variety of
      physiological processes. In recent years, it has been suggested that profiles for
      circulating miRNAs, as well as those for tissue miRNAs, have the potential to be
      used as diagnostic biomarkers for cancer. The aim of this study was to confirm
      the existence of miRNAs in human bile and to assess their potential as clinical
      biomarkers for BTC. We sampled bile from patients who underwent biliary drainage
      for biliary diseases such as BTC and choledocholithiasis. PCR-based miRNA
      detection and miRNA cloning were performed to identify bile miRNAs. Using high
      throughput real-time PCR-based miRNA microarrays, the expression profiles of 667
      miRNAs were compared in patients with malignant disease (n = 9) and age-matched
      patients with the benign disease choledocholithiasis (n = 9). We subsequently
      characterized bile miRNAs in terms of stability and localization. Through cloning
      and using PCR methods, we confirmed that miRNAs exist in bile. Differential
      analysis of bile miRNAs demonstrated that 10 of the 667 miRNAs were significantly
      more highly expressed in the malignant group than in the benign group at
      P<0.0005. Setting the specificity threshold to 100% showed that some miRNAs (miR
      9, miR-302c*, miR-199a-3p and miR-222*) had a sensitivity level of 88.9%, and
      receiver-operating characteristic analysis demonstrated that miR-9 and miR-145*
      could be useful diagnostic markers for BTC. Moreover, we verified the long-term
      stability of miRNAs in bile, a characteristic that makes them suitable for
      diagnostic use in clinical settings. We also confirmed that bile miRNAs are
      localized to the malignant/benign biliary epithelia. These findings suggest that
      bile miRNAs could be informative biomarkers for hepatobiliary disease and that
      some miRNAs, particularly miR-9, may be helpful in the diagnosis and clinical
      management of BTC.

PMID- 21858176
TI  - In vivo safety and persistence of endoribonuclease gene-transduced CD4+ T cells
      in cynomolgus macaques for HIV-1 gene therapy model.
AB  - BACKGROUND: MazF is an endoribonuclease encoded by Escherichia coli that
      specifically cleaves the ACA sequence of mRNA. In our previous report,
      conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes
      resistant to HIV-1 replication. In this study, we examined the in vivo safety and
      persistence of MazF-transduced cynomolgus macaque CD4+ T cells infused into
      autologous monkeys. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo persistence of
      the gene-modified CD4+ T cells in the peripheral blood was monitored for more
      than half a year using quantitative real-time PCR and flow cytometry, followed by
      experimental autopsy in order to examine the safety and distribution pattern of
      the infused cells in several organs. Although the levels of the MazF-transduced
      CD4+ T cells gradually decreased in the peripheral blood, they were clearly
      detected throughout the experimental period. Moreover, the infused cells were
      detected in the distal lymphoid tissues, such as several lymph nodes and the
      spleen. Histopathological analyses of tissues revealed that there were no lesions
      related to the infused gene modified cells. Antibodies against MazF were not
      detected. These data suggest the safety and the low immunogenicity of MazF
      transduced CD4+ T cells. Finally, gene modified cells harvested from the monkey
      more than half a year post-infusion suppressed the replication of SHIV 89.6P.
      CONCLUSIONS/SIGNIFICANCE: The long-term persistence, safety and continuous HIV
      replication resistance of the mazF gene-modified CD4+ T cells in the non-human
      primate model suggests that autologous transplantation of mazF gene-modified
      cells is an attractive strategy for HIV gene therapy.

PMID- 21858177
TI  - Interactions with M cells and macrophages as key steps in the pathogenesis of
      enterohemorrhagic Escherichia coli infections.
AB  - Enterohemorrhagic Escherichia coli (EHEC) are food-borne pathogens that can cause
      serious infections ranging from diarrhea to hemorrhagic colitis (HC) and
      hemolytic-uremic syndrome (HUS). Translocation of Shiga-toxins (Stx) from the gut
      lumen to underlying tissues is a decisive step in the development of the
      infection, but the mechanisms involved remain unclear. Many bacterial pathogens
      target the follicle-associated epithelium, which overlies Peyer's patches (PPs),
      cross the intestinal barrier through M cells and are captured by mucosal
      macrophages. Here, translocation across M cells, as well as survival and
      proliferation of EHEC strains within THP-1 macrophages were investigated using
      EHEC O157:H7 reference strains, isogenic mutants, and 15 EHEC strains isolated
      from HC/HUS patients. We showed for the first time that E. coli O157:H7 strains
      are able to interact in vivo with murine PPs, to translocate ex vivo through
      murine ileal mucosa with PPs and across an in vitro human M cell model. EHEC
      strains are also able to survive and to produce Stx in macrophages, which induce
      cell apoptosis and Stx release. In conclusion, our results suggest that the
      uptake of EHEC by M cells and underlying macrophages in the PP may be a critical
      step in Stx translocation and release in vivo. A new model for EHEC infection in
      humans is proposed that could help in a fuller understanding of EHEC-associated
      diseases.

PMID- 21858178
TI  - Ectopic pregnancy as a model to identify endometrial genes and signaling pathways
      important in decidualization and regulated by local trophoblast.
AB  - The endometrium in early pregnancy undergoes decidualization and functional
      changes induced by local trophoblast, which are not fully understood. We
      hypothesized that endometrium from tubal ectopic pregnancy (EP) could be
      interrogated to identify novel genes and pathways involved in these processes.
      Gestation-matched endometrium was collected from women with EP (n = 11) and
      intrauterine pregnancies (IUP) (n = 13). RNA was extracted from the tissue. In
      addition, tissues were prepared for histological analysis for degree of
      decidualization. We compared a) the samples from EP that were decidualized (n =
      6) with non-decidualized samples (n = 5), and b) the decidualized EP (n = 6) with
      decidualization-matched IUP (n = 6) samples using an Affymetrix gene array
      platform, with Ingenuity Pathway Analysis, combined with quantitative RT-PCR.
      Expression of PRL and IGFBP1 was used to confirm the degree of decidualization in
      each group. There were no differences in PRL or IGFBP1 expression in the
      decidualization-matched samples but a marked reduction (P<0.001) in the non
      decidualized samples. Decidualization was associated with increased expression of
      428 genes including SCARA5 (181-fold), DKK1 (71-fold) and PROK1 (32-fold), and
      decreased expression of 230 genes including MMP-7 (35-fold) and SFRP4 (21-fold).
      The top canonical pathways associated with these differentially expressed genes
      were Natural Killer Cell and Wnt/b-Catenin signaling. Local trophoblast was
      associated with much less alteration of endometrial gene expression with an
      increase in 56 genes, including CSH1 (8-fold), and a reduction in 29 genes
      including CRISP3 (8-fold). The top associated canonical pathway was Antigen
      Presentation. The study of endometrium from tubal EP may promote novel insights
      into genes involved in decidualization and those influenced by factors from
      neighboring trophoblast. This has afforded unique information not highlighted by
      previous studies and adds to our understanding of the endometrium in early
      pregnancy.

PMID- 21858179
TI  - Fluorescence dequenching makes haem-free soluble guanylate cyclase detectable in
      living cells.
AB  - In cardiovascular disease, the protective NO/sGC/cGMP signalling-pathway is
      impaired due to a decreased pool of NO-sensitive haem-containing sGC accompanied
      by a reciprocal increase in NO-insensitive haem-free sGC. However, no direct
      method to detect cellular haem-free sGC other than its activation by the new
      therapeutic class of haem mimetics, such as BAY 58-2667, is available. Here we
      show that fluorescence dequenching, based on the interaction of the optical
      active prosthetic haem group and the attached biarsenical fluorophor FlAsH can be
      used to detect changes in cellular sGC haem status. The partly overlap of the
      emission spectrum of haem and FlAsH allows energy transfer from the fluorophore
      to the haem which reduces the intensity of FlAsH fluorescence. Loss of the
      prosthetic group, e.g. by oxidative stress or by replacement with the haem
      mimetic BAY 58-2667, prevented the energy transfer resulting in increased
      fluorescence. Haem loss was corroborated by an observed decrease in NO-induced
      sGC activity, reduced sGC protein levels, and an increased effect of BAY 58-2667.
      The use of a haem-free sGC mutant and a biarsenical dye that was not quenched by
      haem as controls further validated that the increase in fluorescence was due to
      the loss of the prosthetic haem group. The present approach is based on the
      cellular expression of an engineered sGC variant limiting is applicability to
      recombinant expression systems. Nevertheless, it allows to monitor sGC's redox
      regulation in living cells and future enhancements might be able to extend this
      approach to in vivo conditions.

PMID- 21858180
TI  - Functional and spatial analysis of C. elegans SYG-1 and SYG-2, orthologs of the
      Neph/nephrin cell adhesion module directing selective synaptogenesis.
AB  - The assembly of specific synaptic connections represents a prime example of
      cellular recognition. Members of the Ig superfamily are among the most ancient
      proteins represented in the genomes of both mammalian and invertebrate organisms,
      where they constitute a trans-synaptic adhesion system. The correct connectivity
      patterns of the highly conserved immunoglobulin superfamily proteins nephrin and
      Neph1 are crucial for the assembly of functional neuronal circuits and the
      formation of the kidney slit diaphragm, a synapse-like structure forming the
      filtration barrier. Here, we utilize the nematode C. elegans model for studying
      the requirements of synaptic specificity mediated by nephrin-Neph proteins. In C.
      elegans, the nephrin/Neph1 orthologs SYG-2 and SYG-1 form intercellular contacts
      strictly in trans between epithelial guidepost cells and neurons specifying the
      localization of synapses. We demonstrate a functional conservation between
      mammalian nephrin and SYG-2. Expression of nephrin effectively compensated loss
      of syg-2 function in C. elegans and restored defective synaptic connectivity
      further establishing the C. elegans system as a valuable model for slit diaphragm
      proteins. Next, we investigated the effect of SYG-1 and SYG-2 trans
      homodimerization respectively. Strikingly, synapse assembly could be induced by
      homophilic SYG-1 but not SYG-2 binding indicating a critical role of SYG-1
      intracellular signalling for morphogenetic events and pointing toward the dynamic
      and stochastic nature of extra- and intracellular nephrin-Neph interactions to
      generate reproducible patterns of synaptic connectivity.

PMID- 21858181
TI  - Yes, I am ready now: differential effects of paced versus unpaced mating on
      anxiety and central oxytocin release in female rats.
AB  - Sexual activity and partner intimacy results in several positive consequences in
      the context of stress-coping, both in males and females, such as reduced state
      anxiety in male rats after successful mating. However, in female rats, mating is
      a rewarding experience only when the estrous female is able to control sexual
      interactions, i.e., under paced-mating conditions. Here, we demonstrate that sex
      steroid priming required for female mating is anxiolytic; subsequent sexual
      activity under paced mating conditions did not disrupt this anxiolytic priming
      effect, whereas mating under unpaced conditions increased anxiety-related
      behavior. In primed females, the release of the neuropeptide oxytocin (OT) within
      the hypothalamic paraventricular nucleus was found to be elevated and to further
      increase during paced, but not unpaced mating. Central administration of an OT
      receptor antagonist partly prevented priming/mating-induced anxiolysis indicating
      the involvement of brain OT in the anxiolysis triggered by priming and/or sexual
      activity.These findings reveal that the positive consequences of mating in
      females are dependent on her ability to control sexual interactions, and that
      brain OT release is at least in part the underlying neurobiological correlate.

PMID- 21858182
TI  - Soluble beta-amyloid precursor protein is related to disease progression in
      amyotrophic lateral sclerosis.
AB  - BACKGROUND: Biomarkers of disease progression in amyotrophic lateral sclerosis
      (ALS) could support the identification of beneficial drugs in clinical trials. We
      aimed to test whether soluble fragments of beta-amyloid precursor protein
      (sAPPalpha and sAPPbeta) correlated with clinical subtypes of ALS and were of
      prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study
      including patients with ALS (N = 68) with clinical follow-up data over 6 months,
      Parkinson's disease (PD, N = 20), and age-matched controls (N = 40),
      cerebrospinal fluid (CSF) levels of sAPPalpha a, sAPPbeta and neurofilaments
      (NfH(SMI35)) were measured by multiplex assay, Progranulin by ELISA. CSF
      sAPPalpha and sAPPbeta levels were lower in ALS with a rapidly-progressive
      disease course (p = 0.03, and p = 0.02) and with longer disease duration (p =
      0.01 and p = 0.01, respectively). CSF NfH(SMI35) was elevated in ALS compared to
      PD and controls, with highest concentrations found in patients with rapid disease
      progression (p<0.01). High CSF NfH(SMI3) was linked to low CSF sAPPalpha and
      sAPPbeta (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH(SMI35)/CSF
      sAPPalpha,-beta were elevated in patients with fast progression of disease (p =
      0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04).
      CONCLUSIONS: This study provides new CSF candidate markers associated with
      progression of disease in ALS. The data suggest that a deficiency of cellular
      neuroprotective mechanisms (decrease of sAPP) is linked to progressive neuro
      axonal damage (increase of NfH(SMI35)) and to progression of disease.

PMID- 21858183
TI  - Large recovery of fish biomass in a no-take marine reserve.
AB  - No-take marine reserves are effective management tools used to restore fish
      biomass and community structure in areas depleted by overfishing. Cabo Pulmo
      National Park (CPNP) was created in 1995 and is the only well enforced no-take
      area in the Gulf of California, Mexico, mostly because of widespread support from
      the local community. In 1999, four years after the establishment of the reserve,
      there were no significant differences in fish biomass between CPNP (0.75 t ha(-1)
      on average) and other marine protected areas or open access areas in the Gulf of
      California. By 2009, total fish biomass at CPNP had increased to 4.24 t ha(-1)
      (absolute biomass increase of 3.49 t ha(-1), or 463%), and the biomass of top
      predators and carnivores increased by 11 and 4 times, respectively. However, fish
      biomass did not change significantly in other marine protected areas or open
      access areas over the same time period. The absolute increase in fish biomass at
      CPNP within a decade is the largest measured in a marine reserve worldwide, and
      it is likely due to a combination of social (strong community leadership, social
      cohesion, effective enforcement) and ecological factors. The recovery of fish
      biomass inside CPNP has resulted in significant economic benefits, indicating
      that community-managed marine reserves are a viable solution to unsustainable
      coastal development and fisheries collapse in the Gulf of California and
      elsewhere.

PMID- 21858184
TI  - Quality of reporting of bioequivalence trials comparing generic to brand name
      drugs: a methodological systematic review.
AB  - BACKGROUND: Generic drugs are used by millions of patients for economic reasons,
      so their evaluation must be highly transparent. OBJECTIVE: To assess the quality
      of reporting of bioequivalence trials comparing generic to brand-name drugs.
      METHODOLOGY/PRINCIPAL FINDINGS: PubMed was searched for reports of bioequivalence
      trials comparing generic to brand-name drugs between January 2005 and December
      2008. Articles were included if the aim of the study was to assess the
      bioequivalency of generic and brand-name drugs. We excluded case studies,
      pharmaco-economic evaluations, and validation dosage assays of drugs. We
      evaluated whether important information about funding, methodology, location of
      trials, and participants were reported. We also assessed whether the criteria
      required by the Food and Drug Administration (FDA) and the European Medicine
      Agency (EMA) to conclude bioequivalence were reported and that the conclusions
      were in agreement with the results. We identified 134 potentially relevant
      articles but eliminated 55 because the brand-name or generic drug status of the
      reference drug was unknown. Thus, we evaluated 79 articles. The funding source
      and location of the trial were reported in 41% and 56% of articles, respectively.
      The type of statistical analysis was reported in 94% of articles, but the methods
      to generate the randomization sequence and to conceal allocation were reported in
      only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%)
      concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within
      the limits required by the FDA and 11 (17%) did not report the 2 criteria within
      the limits required by the EMA. CONCLUSIONS/SIGNIFICANCE: Important information
      to judge the validity and relevance of results are frequently missing in
      published reports of trials assessing generic drugs. The quality of reporting of
      such trials is in need of improvement.

PMID- 21858185
TI  - Testing multiple coordination constraints with a novel bimanual visuomotor task.
AB  - The acquisition of a new bimanual skill depends on several motor coordination
      constraints. To date, coordination constraints have often been tested relatively
      independently of one another, particularly with respect to isofrequency and
      multifrequency rhythms. Here, we used a new paradigm to test the interaction of
      multiple coordination constraints. Coordination constraints that were tested
      included temporal complexity, directionality, muscle grouping, and hand
      dominance. Twenty-two healthy young adults performed a bimanual dial rotation
      task that required left and right hand coordination to track a moving target on a
      computer monitor. Two groups were compared, either with or without four days of
      practice with augmented visual feedback. Four directional patterns were tested
      such that both hands moved either rightward (clockwise), leftward
      (counterclockwise), inward or outward relative to each other. Seven frequency
      ratios (3?1, 2?1, 3?2, 1?1, 2?3. 1?2, 1?3) between the left and right hand were
      introduced. As expected, isofrequency patterns (1?1) were performed more
      successfully than multifrequency patterns (non 1?1). In addition, performance was
      more accurate when participants were required to move faster with the dominant
      right hand (1?3, 1?2 and 2?3) than with the non-dominant left hand (3?1, 2?1,
      3?2). Interestingly, performance deteriorated as the relative angular velocity
      between the two hands increased, regardless of whether the required frequency
      ratio was an integer or non-integer. This contrasted with previous finger tapping
      research where the integer ratios generally led to less error than the non
      integer ratios. We suggest that this is due to the different movement topologies
      that are required of each paradigm. Overall, we found that this visuomotor task
      was useful for testing the interaction of multiple coordination constraints as
      well as the release from these constraints with practice in the presence of
      augmented visual feedback.

PMID- 21858186
TI  - Real time enzyme inhibition assays provide insights into differences in binding
      of neuraminidase inhibitors to wild type and mutant influenza viruses.
AB  - The influenza neuraminidase (NA) inhibitors zanamivir, oseltamivir and peramivir
      were all designed based on the knowledge that the transition state analogue of
      the cleaved sialic acid, 2-deoxy,2,3-dehydro N-acetyl neuraminic acid (DANA) was
      a weak inhibitor of NA. While DANA bound rapidly to the NA, modifications leading
      to the improved potency of these new inhibitors also conferred a time dependent
      or slow binding phenotype. Many mutations in the NA leading to decreased
      susceptibility result in loss of slow binding, hence this is a phenotypic marker
      of many but not all resistant NAs. We present here a simplified approach to
      determine whether an inhibitor is fast or slow binding by extending the endpoint
      fluorescent enzyme inhibition assay to a real time assay and monitoring the
      changes in IC(50)s with time. We carried out two reactions, one with a 30 min
      preincubation with inhibitor and the second without. The enzymatic reaction was
      started via addition of substrate and IC(50)s were calculated after each 10 min
      interval up to 60 min. Results showed that without preincubation IC(50)s for the
      wild type viruses started high and although they decreased continuously over the
      60 min reaction time the final IC(50)s remained higher than for pre-incubated
      samples. These results indicate a slow equilibrium of association and
      dissociation and are consistent with slow binding of the inhibitors. In contrast,
      for viruses with decreased susceptibility, preincubation had minimal effect on
      the IC(50)s, consistent with fast binding. Therefore this modified assay provides
      additional phenotypic information about the rate of inhibitor binding in addition
      to the IC(50), and critically demonstrates the differential effect of incubation
      times on the IC(50) and K(i) values of wild type and mutant viruses for each of
      the inhibitors.

PMID- 21858187
TI  - Rhythmic diel pattern of gene expression in juvenile maize leaf.
AB  - BACKGROUND: Numerous biochemical and physiological parameters of living organisms
      follow a circadian rhythm. Although such rhythmic behavior is particularly
      pronounced in plants, which are strictly dependent on the daily photoperiod, data
      on the molecular aspects of the diurnal cycle in plants is scarce and mostly
      concerns the model species Arabidopsis thaliana. Here we studied the leaf
      transcriptome in seedlings of maize, an important C4 crop only distantly related
      to A. thaliana, throughout a cycle of 10 h darkness and 14 h light to look for
      rhythmic patterns of gene expression. RESULTS: Using DNA microarrays comprising
      ca. 43,000 maize-specific probes we found that ca. 12% of all genes showed clear
      cut diel rhythms of expression. Cluster analysis identified 35 groups containing
      from four to ca. 1,000 genes, each comprising genes of similar expression
      patterns. Perhaps unexpectedly, the most pronounced and most common (concerning
      the highest number of genes) expression maxima were observed towards and during
      the dark phase. Using Gene Ontology classification several meaningful functional
      associations were found among genes showing similar diel expression patterns,
      including massive induction of expression of genes related to gene expression,
      translation, protein modification and folding at dusk and night. Additionally, we
      found a clear-cut tendency among genes belonging to individual clusters to share
      defined transcription factor-binding sequences. CONCLUSIONS: Co-expressed genes
      belonging to individual clusters are likely to be regulated by common mechanisms.
      The nocturnal phase of the diurnal cycle involves gross induction of fundamental
      biochemical processes and should be studied more thoroughly than was appreciated
      in most earlier physiological studies. Although some general mechanisms
      responsible for the diel regulation of gene expression might be shared among
      plants, details of the diurnal regulation of gene expression seem to differ
      between taxa.

PMID- 21858188
TI  - Trabecular reorganization in consecutive iliac crest biopsies when switching from
      bisphosphonate to strontium ranelate treatment.
AB  - BACKGROUND: Several agents are available to treat osteoporosis while addressing
      patient-specific medical needs. Individuals' residual risk to severe fracture may
      require changes in treatment strategy. Data at osseous cellular and
      microstructural levels due to a therapy switch between agents with different
      modes of action are rare. Our study on a series of five consecutively taken bone
      biopsies from an osteoporotic individual over a six-year period analyzes changes
      in cellular characteristics, bone microstructure and mineralization caused by a
      therapy switch from an antiresorptive (bisphosphonate) to a dual action bone
      agent (strontium ranelate). METHODOLOGY/PRINCIPAL FINDINGS: Biopsies were
      progressively taken from the iliac crest of a female patient. Four biopsies were
      taken during bisphosphonate therapy and one biopsy was taken after one year of
      strontium ranelate (SR) treatment. Furthermore, serum bone markers and dual x-ray
      absorptiometry measurements were acquired. Undecalcified histology was used to
      assess osteoid parameters and bone turnover. Structural indices and degree of
      mineralization were determined using microcomputed tomography, quantitative
      backscattered electron imaging, and combined energy dispersive x-ray/u-x-ray
      fluorescence microanalysis. CONCLUSIONS/SIGNIFICANCE: Microstructural data
      revealed a notable increase in bone volume fraction after one year of SR
      treatment compared to the bisphosphonate treatment period. Indices of
      connectivity density, structure model index and trabecular bone pattern factor
      were predominantly enhanced indicating that the architectural transformation from
      trabecular rods to plates was responsible for the bone volume increase and less
      due to changes in trabecular thickness and number. Administration of SR following
      bisphosphonates led to a maintained mineralization profile with an uptake of
      strontium on the bone surface level. Reactivated osteoclasts designed tunneling,
      hook-like intratrabecular resorption sites. The appearance of tunneling
      resorption lacunae and the formation of both mini-modeling units and osteon-like
      structures within increased plate-like cancellous bone mass provides additional
      information on the mechanisms of strontium ranelate following bisphosphonate
      treatment, which may deserve special attention when monitoring a treatment
      switch.

PMID- 21858189
TI  - Variation in the male pheromones and mating success of wild caught Drosophila
      melanogaster.
AB  - Drosophila melanogaster males express two primary cuticular hydrocarbons (male
      predominant hydrocarbons). These act as sex pheromones by influencing female
      receptivity to mating. The relative quantities of these hydrocarbons vary widely
      among natural populations and can contribute to variation in mating success. We
      tested four isofemale lines collected from a wild population to assess the effect
      of intrapopulation variation in male-predominant hydrocarbons on mating success.
      The receptivity of laboratory females to males of the four wild-caught lines
      varied significantly, but not consistently in the direction predicted by
      variation in male-predominant hydrocarbons. Receptivity of the wild-caught
      females to laboratory males also varied significantly, but females from lines
      with male-predominant hydrocarbon profiles closer to a more cosmopolitan one did
      not show a correspondingly strong mating bias toward a cosmopolitan male. Among
      wild-caught lines, the male-specific ejaculatory bulb lipid, cis-vaccenyl
      acetate, varied more than two-fold, but was not associated with variation in male
      mating success. We observed a strong inverse relationship between the receptivity
      of wild-caught females and the mating success of males from their own lines, when
      tested with laboratory flies of the opposite sex.

PMID- 21858190
TI  - N-termini of fungal CSL transcription factors are disordered, enriched in
      regulatory motifs and inhibit DNA binding in fission yeast.
AB  - BACKGROUND: CSL (CBF1/RBP-Jkappa/Suppressor of Hairless/LAG-1) transcription
      factors are the effector components of the Notch receptor signalling pathway,
      which is critical for metazoan development. The metazoan CSL proteins (class M)
      can also function in a Notch-independent manner. Recently, two novel classes of
      CSL proteins, designated F1 and F2, have been identified in fungi. The role of
      the fungal CSL proteins is unclear, because the Notch pathway is not present in
      fungi. In fission yeast, the Cbf11 and Cbf12 CSL paralogs play antagonistic roles
      in cell adhesion and the coordination of cell and nuclear division. Unusually
      long N-terminal extensions are typical for fungal and invertebrate CSL family
      members. In this study, we investigate the functional significance of these
      extended N-termini of CSL proteins. METHODOLOGY/PRINCIPAL FINDINGS: We identify
      15 novel CSL family members from 7 fungal species and conduct bioinformatic
      analyses of a combined dataset containing 34 fungal and 11 metazoan CSL protein
      sequences. We show that the long, non-conserved N-terminal tails of fungal CSL
      proteins are likely disordered and enriched in phosphorylation sites and PEST
      motifs. In a case study of Cbf12 (class F2), we provide experimental evidence
      that the protein is proteolytically processed and that the N-terminus inhibits
      the Cbf12-dependent DNA binding activity in an electrophoretic mobility shift
      assay. CONCLUSIONS/SIGNIFICANCE: This study provides insight into the
      characteristics of the long N-terminal tails of fungal CSL proteins that may be
      crucial for controlling DNA-binding and CSL function. We propose that the
      regulation of DNA binding by Cbf12 via its N-terminal region represents an
      important means by which fission yeast strikes a balance between the class F1 and
      class F2 paralog activities. This mode of regulation might be shared with other
      CSL-positive fungi, some of which are relevant to human disease and
      biotechnology.

PMID- 21858191
TI  - Split T cell tolerance against a self/tumor antigen: spontaneous CD4+ but not
      CD8+ T cell responses against p53 in cancer patients and healthy donors.
AB  - Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients
      revealed that antibody and both CD4(+) and CD8(+) T cell responses were induced
      together in cancer patients. To explore whether such integrated immune responses
      are also spontaneously induced for other tumor antigens, we have evaluated
      antibody and T cell responses against self/tumor antigen p53 in ovarian cancer
      patients and healthy individuals. We found that 21% (64/298) of ovarian cancer
      patients but no healthy donors showed specific IgG responses against wild-type
      p53 protein. While none of 12 patients with high titer p53 antibody showed
      spontaneous p53-specific CD8(+) T cell responses following a single in vitro
      sensitization, significant p53-specific IFN-gamma producing CD4(+) T cells were
      detected in 6 patients. Surprisingly, similar levels of p53-specific CD4(+) T
      cells but not CD8(+) T cells were also detected in 5/10 seronegative cancer
      patients and 9/12 healthy donors. Importantly, p53-specific CD4(+) T cells in
      healthy donors originated from a CD45RA(-) antigen-experienced T cell population
      and recognized naturally processed wild-type p53 protein. These results raise the
      possibility that p53-specific CD4(+) T cells reflect abnormalities in p53
      occurring in normal individuals and that they may play a role in processes of
      immunosurveillance or immunoregulation of p53-related neoplastic events.

PMID- 21858192
TI  - Longevity in mice is promoted by probiotic-induced suppression of colonic
      senescence dependent on upregulation of gut bacterial polyamine production.
AB  - BACKGROUND: Chronic low-grade inflammation is recognized as an important factor
      contributing to senescence and age-related diseases. In mammals, levels of
      polyamines (PAs) decrease during the ageing process; PAs are known to decrease
      systemic inflammation by inhibiting inflammatory cytokine synthesis in
      macrophages. Reductions in intestinal luminal PAs levels have been associated
      with intestinal barrier dysfunction. The probiotic strain Bifidobacterium
      animalis subsp. lactis LKM512 is known to increase intestinal luminal PA
      concentrations. METHODOLOGY/PRINCIPAL FINDINGS: We supplemented the diet of 10
      month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls
      received no supplementation. Survival rates were compared using Kaplan-Meier
      survival curves. LKM512-treated mice survived significantly longer than controls
      (P<0.001); moreover, skin ulcers and tumors were more common in the control mice.
      We then analyzed inflammatory and intestinal conditions by measuring several
      markers using HPLC, ELISA, reverse transcription-quantitative PCR, and
      histological slices. LKM512 mice showed altered 16S rRNA gene expression of
      several predominant intestinal bacterial groups. The fecal concentrations of PAs,
      but not of short-chain fatty acids, were significantly higher in LKM512-treated
      mice (P<0.05). Colonic mucosal function was also better in LKM512 mice, with
      increased mucus secretion and better maintenance of tight junctions. Changes in
      gene expression levels were evaluated using the NimbleGen mouse DNA microarray.
      LKM512 administration also downregulated the expression of ageing-associated and
      inflammation-associated genes and gene expression levels in 21-month-old LKM512
      treated mice resembled those in 10-month-old untreated (younger) mice.
      CONCLUSION/SIGNIFICANCE: Our study demonstrated increased longevity in mice
      following probiotic treatment with LKM512, possibly due to the suppression of
      chronic low-grade inflammation in the colon induced by higher PA levels. This
      indicates that ingestion of specific probiotics may be an easy approach for
      improving intestinal health and increasing lifespan. Further studies are required
      to clarify its effectiveness in humans.

PMID- 21858193
TI  - Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via
      nuclear factor-kappa B.
AB  - Inflammation and oxidative stress have been implicated in the pathophysiology of
      Parkinson's disease (PD) and inhibition of microglial activation attenuates
      degeneration of dopaminergic (DA) neurons in animal models of PD. Loss-of
      function mutations in the parkin gene, which encodes an E3 ubiquitin ligase,
      cause autosomal recessive parkinsonism. While most studies on Parkin have focused
      on its function in neurons, here we demonstrate that Parkin mRNA and protein is
      detectable in brain-resident microglia and peripheral macrophages. Using
      pharmacologic and genetic approaches, we found that Parkin levels are regulated
      by inflammatory signaling. Specifically, exposure to LPS or Tumor Necrosis Factor
      (TNF) induced a transient and dose-dependent decrease in Parkin mRNA and protein
      in microglia, macrophages and neuronal cells blockable by inhibitors of Nuclear
      Factor-Kappa B (NF-kappaB) signaling and not observed in MyD88-null cells.
      Moreover, using luciferase reporter assays, we identified an NF-kappaB response
      element in the mouse parkin promoter responsible for mediating the
      transcriptional repression, which was abrogated when the consensus sequence was
      mutated. Functionally, activated macrophages from Parkin-null mice displayed
      increased levels of TNF, IL-1beta, and iNOS mRNA compared to wild type
      macrophages but no difference in levels of Nrf2, HO-1, or NQO1. One implication
      of our findings is that chronic inflammatory conditions may reduce Parkin levels
      and phenocopy parkin loss-of-function mutations, thereby increasing the
      vulnerability for degeneration of the nigrostriatal pathway and development of
      PD.

PMID- 21858194
TI  - Regulation of apoptotic effects by erythrocarpine E, a cytotoxic limonoid from
      Chisocheton erythrocarpus in HSC-4 human oral cancer cells.
AB  - The aim of this study was to determine the cytotoxic and apoptotic effects of
      erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on
      human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5
      diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells
      demonstrated a cytotoxic effect and inhibited cell proliferation in a time and
      dose dependent manner with an IC(50) value of 4.0+/-1.9 uM within 24 h of
      treatment. CEB4 was also found to have minimal cytotoxic effects on the normal
      cell line, NHBE with cell viability levels maintained above 80% upon treatment.
      Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP)
      cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis
      mediated cell death. Western blotting results demonstrated that the induction of
      apoptosis by CEB4 appeared to be mediated through regulation of the p53
      signalling pathway as there was an increase in p53 phosphorylation levels. CEB4
      was also found to up-regulate the pro-apoptotic protein, Bax, while down
      regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the
      intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and
      executioner caspase-3 zymogen were also observed following CEB4 exposure, hence
      indicating the involvement of cytochrome c mediated apoptosis. These results
      demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest
      its potential development as a cancer chemopreventive agent.

PMID- 21858195
TI  - Sodium-calcium exchange in intracellular calcium handling of human airway smooth
      muscle.
AB  - Enhanced airway contractility following inflammation by cytokines such as tumor
      necrosis factor alpha (TNFalpha) or interleukin-13 (IL-13) involves increased
      intracellular Ca(2+) ([Ca(2+)](i)) levels in airway smooth muscle (ASM). In ASM,
      plasma membrane Ca(2+) fluxes form a key component of [Ca(2+)](i) regulation.
      There is now growing evidence that the bidirectional plasma membrane Na(+)/Ca(2+)
      exchanger (NCX) contributes to ASM [Ca(2+)](i) regulation. In the present study,
      we examined NCX expression and function in human ASM cells under normal
      conditions, and following exposure to TNFalpha or IL-13. Western blot analysis
      showed significant expression of the NCX1 isoform, with increased NCX1 levels by
      both cytokines, effects blunted by inhibitors of nuclear factor NF-kappaB or
      mitogen-activated protein kinase. Cytokine-mediated increase in NCX1 involved
      enhanced transcription followed by protein synthesis. NCX2 and NCX3 remained
      undetectable even in cytokine-stimulated ASM. In fura-2 loaded human ASM cells,
      NCX-mediated inward Ca(2+) exchange as well as outward exchange (measured as
      rates of change in [Ca(2+)](i)) was elicited by altering extracellular Na(+) and
      Ca(2+) levels. Contribution of NCX was verified by measuring [Na(+)](i) using the
      fluorescent Na(+) indicator SBFI. NCX-mediated inward exchange was verified by
      demonstrating prevention of rising [Ca(2+)](i) or falling [Na(+)](i) in the
      presence of the NCX inhibitor KBR7943. Inward exchange-mode NCX was increased by
      both TNFalpha and IL-13 to a greater extent than outward exchange. NCX siRNA
      transfection substantially blunted outward exchange and inward exchange modes.
      Finally, inhibition of NCX expression or function blunted peak [Ca(2+)](i) and
      rate of fall of [Ca(2+)](i) following histamine stimulation. These data suggest
      that NCX-mediated Ca(2+) fluxes normally exist in human ASM (potentially
      contributing to rapid Ca(2+) fluxes), and contribute to enhanced [Ca(2+)](i)
      regulation in airway inflammation.

PMID- 21858196
TI  - Dynamic changes in EPCAM expression during spermatogonial stem cell
      differentiation in the mouse testis.
AB  - BACKGROUND: Spermatogonial stem cells (SSCs) have the unique ability to undergo
      self-renewal division. However, these cells are morphologically indistinguishable
      from committed spermatogonia, which have limited mitotic activity. To establish a
      system for SSC purification, we analyzed the expression of SSC markers CD9 and
      epithelial cell adhesion molecule (EPCAM), both of which are also expressed on
      embryonic stem (ES) cells. We examined the correlation between their expression
      patterns and SSC activities. METHODOLOGY AND PRINCIPAL FINDINGS: By magnetic cell
      sorting, we found that EPCAM-selected mouse germ cells have limited clonogenic
      potential in vitro. Moreover, these cells showed stronger expression of
      progenitor markers than CD9-selected cells, which are significantly more enriched
      in SSCs. Fluorescence-activated cell sorting of CD9-selected cells indicated a
      significantly higher frequency of SSCs among the CD9(+)EPCAM(low/-) population
      than among the CD9(+)EPCAM(+) population. Overexpression of the active form of
      EPCAM in germline stem (GS) cell cultures did not significantly influence SSC
      activity, whereas EPCAM suppression by short hairpin RNA compromised GS cell
      proliferation and increased the concentration of SSCs, as revealed by germ cell
      transplantation. CONCLUSIONS/SIGNIFICANCE: These results show that SSCs are the
      most concentrated in CD9(+)EPCAM(low/-) population and also suggest that EPCAM
      plays an important role in progenitor cell amplification in the mouse
      spermatogenic system. The establishment of a method to distinguish progenitor
      spermatogonia from SSCs will be useful for developing an improved purification
      strategy for SSCs from testis cells.

PMID- 21858197
TI  - There is no safe dose of prions.
AB  - Understanding the circumstances under which exposure to transmissible spongiform
      encephalopathies (TSEs) leads to infection is important for managing risks to
      public health. Based upon ideas in toxicology and radiology, it is plausible that
      exposure to harmful agents, including TSEs, is completely safe if the dose is low
      enough. However, the existence of a threshold, below which infection probability
      is zero has never been demonstrated experimentally. Here we explore this question
      by combining data and mathematical models that describe scrapie infections in
      mice following experimental challenge over a broad range of doses. We analyse
      data from 4338 mice inoculated at doses ranging over ten orders of magnitude.
      These data are compared to results from a within-host model in which prions
      accumulate according to a stochastic birth-death process. Crucially, this model
      assumes no threshold on the dose required for infection. Our data reveal that
      infection is possible at the very low dose of a 1000 fold dilution of the dose
      that infects half the challenged animals (ID50). Furthermore, the dose response
      curve closely matches that predicted by the model. These findings imply that
      there is no safe dose of prions and that assessments of the risk from low dose
      exposure are right to assume a linear relationship between dose and probability
      of infection. We also refine two common perceptions about TSE incubation periods:
      that their mean values decrease linearly with logarithmic decreases in dose and
      that they are highly reproducible between hosts. The model and data both show
      that the linear decrease in incubation period holds only for doses above the
      ID50. Furthermore, variability in incubation periods is greater than predicted by
      the model, not smaller. This result poses new questions about the sources of
      variability in prion incubation periods. It also provides insight into the
      limitations of the incubation period assay.

PMID- 21858198
TI  - A conserved tissue-specific homeodomain-less isoform of MEIS1 is downregulated in
      colorectal cancer.
AB  - Colorectal cancer is one of the most common cancers in developed nations and is
      the result of both environmental and genetic factors. Many of the genetic lesions
      observed in colorectal cancer alter expression of homeobox genes, which encode
      homeodomain transcription factors. The MEIS1 homeobox gene is known to be
      involved in several hematological malignancies and solid tumors and recent
      evidence suggests that expression of the MEIS1 transcript is altered in
      colorectal cancer. Despite this potential connection, little is known about the
      role of the gene in the intestines. We probed murine gastrointestinal tissue
      samples with an N-terminal Meis1 antibody, revealing expression of two previously
      described isoforms, as well as two novel Meis1 products. A 32 kD Meis1 product
      was expressed in the nuclei of non-epithelial cells in the stomach and colon,
      while a 27 kD product was expressed in the cytoplasm of epithelial cells in the
      proximal colon. Our data suggest that the 27 kD and 32 kD Meis1 proteins are both
      forms of the Meis1d protein, a homeodomain-less isoform whose transcript was
      previously identified in cDNA screens. Both the MEIS1D transcript and protein
      were expressed in human colon mucosa. Expression of the MEIS1D protein was
      downregulated in 83% (10/12) of primary colorectal cancer samples compared to
      matched normal mucosa, indicating that MEIS1D is a biomarker of colorectal
      tumorigenesis. The decreased expression of MEIS1D in colon tumors also suggests
      that this conserved homeodomain-less isoform may act as a tumor suppressor in
      human colorectal cancer.

PMID- 21858199
TI  - Biochemical characterization of a structure-specific resolving enzyme from
      Sulfolobus islandicus rod-shaped virus 2.
AB  - Sulfolobus islandicus rod shaped virus 2 (SIRV2) infects the archaeon Sulfolobus
      islandicus at extreme temperature (70 degrees C-80 degrees C) and acidity (pH 3).
      SIRV2 encodes a Holliday junction resolving enzyme (SIRV2 Hjr) that has been
      proposed as a key enzyme in SIRV2 genome replication. The molecular mechanism for
      SIRV2 Hjr four-way junction cleavage bias, minimal requirements for four-way
      junction cleavage, and substrate specificity were determined. SIRV2 Hjr cleaves
      four-way DNA junctions with a preference for cleavage of exchange strand pairs,
      in contrast to host-derived resolving enzymes, suggesting fundamental differences
      in substrate recognition and cleavage among closely related Sulfolobus resolving
      enzymes. Unlike other viral resolving enzymes, such as T4 endonuclease VII or T7
      endonuclease I, that cleave branched DNA replication intermediates, SIRV2 Hjr
      cleavage is specific to four-way DNA junctions and inactive on other branched DNA
      molecules. In addition, a specific interaction was detected between SIRV2 Hjr and
      the SIRV2 virion body coat protein (SIRV2gp26). Based on this observation, a
      model is proposed linking SIRV2 Hjr genome resolution to viral particle assembly.

PMID- 21858200
TI  - Mast cells are critical for protection against peptic ulcers induced by the NSAID
      piroxicam.
AB  - Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause
      gastrointestinal toxicity, including the development of life-threatening peptic
      ulcers. We report that mast cell-deficient mice have an extremely high incidence
      of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced
      ulcer susceptibility can be reversed by reconstitution with mast cells.
      Furthermore, wild type mice treated with diphenhydramine hydrochloride, a
      commonly used antihistamine that blocks histamine H1 receptors, develop a
      similarly high incidence of peptic ulcers following piroxicam exposure. The
      protective effect of mast cells is independent of TNF, blockade of H2 receptors,
      or acid secretion. These data indicate a critical role for mast cells and the
      histamine that they produce in prevention and/or repair of piroxicam-induced
      gastric mucosal injury. Additional studies will be required to determine whether
      this represents a NSAID class effect that can be exploited to develop novel
      therapeutic strategies to limit the incidence of NSAID-induced side effects in
      humans.

PMID- 21858201
TI  - Species accumulation curves and incidence-based species richness estimators to
      appraise the diversity of cultivable yeasts from beech forest soils.
AB  - BACKGROUND: Yeast-like fungi inhabit soils throughout all climatic zones in a
      great abundance. While recent estimations predicted a plethora of prokaryotic
      taxa in one gram of soil, similar data are lacking for fungi, especially yeasts.
      METHODOLOGY/PRINCIPAL FINDINGS: We assessed the diversity of soil yeasts in
      different forests of central Germany using cultivation-based techniques with
      subsequent identification based on rDNA sequence data. Based on experiments using
      various pre-cultivation sample treatment and different cultivation media we
      obtained the highest number of yeasts by analysing mixed soil samples with a
      single nutrient-rich medium. Additionally, several species richness estimators
      were applied to incidence-based data of 165 samples. All of them predicted a
      similar range of yeast diversity, namely 14 to 16 species. Randomized species
      richness curves reached saturation in all applied estimators, thus indicating
      that the majority of species is detected after approximately 30 to 50 samples
      analysed. CONCLUSIONS/SIGNIFICANCE: In this study we demonstrate that robust
      species identification as well as mathematical approaches are essential to
      reliably estimate the sampling effort needed to describe soil yeast communities.
      This approach has great potential for optimisation of cultivation techniques and
      allows high throughput analysis in the future.

PMID- 21858202
TI  - Unfertilized Xenopus eggs die by Bad-dependent apoptosis under the control of
      Cdk1 and JNK.
AB  - Ovulated eggs possess maternal apoptotic execution machinery that is inhibited
      for a limited time. The fertilized eggs switch off this time bomb whereas aged
      unfertilized eggs and parthenogenetically activated eggs fail to stop the timer
      and die. To investigate the nature of the molecular clock that triggers the egg
      decision of committing suicide, we introduce here Xenopus eggs as an in vivo
      system for studying the death of unfertilized eggs. We report that after
      ovulation, a number of eggs remains in the female body where they die by
      apoptosis. Similarly, ovulated unfertilized eggs recovered in the external medium
      die within 72 h. We showed that the death process depends on both cytochrome c
      release and caspase activation. The apoptotic machinery is turned on during
      meiotic maturation, before fertilization. The death pathway is independent of ERK
      but relies on activating Bad phosphorylation through the control of both kinases
      Cdk1 and JNK. In conclusion, the default fate of an unfertilized Xenopus egg is
      to die by a mitochondrial dependent apoptosis activated during meiotic
      maturation.

PMID- 21858203
TI  - Urokinase plasminogen activator inhibits HIV virion release from macrophage
      differentiated chronically infected cells via activation of RhoA and PKCepsilon.
AB  - BACKGROUND: HIV replication in mononuclear phagocytes is a multi-step process
      regulated by viral and cellular proteins with the peculiar feature of virion
      budding and accumulation in intra-cytoplasmic vesicles. Interaction of urokinase
      type plasminogen activator (uPA) with its cell surface receptor (uPAR) has been
      shown to favor virion accumulation in such sub-cellular compartment in primary
      monocyte-derived macrophages and chronically infected promonocytic U1 cells
      differentiated into macrophage-like cells by stimulation with phorbol myristate
      acetate (PMA). By adopting this latter model system, we have here investigated
      which intracellular signaling pathways were triggered by uPA/uPAR interaction
      leading the redirection of virion accumulation in intra-cytoplasmic vesicles.
      RESULTS: uPA induced activation of RhoA, PKCdelta and PKCepsilon in PMA
      differentiated U1 cells. In the same conditions, RhoA, PKCdelta and PKCepsilon
      modulated uPA-induced cell adhesion and polarization, whereas only RhoA and
      PKCepsilon were also responsible for the redirection of virions in intracellular
      vesicles. Distribution of G and F actin revealed that uPA reorganized the
      cytoskeleton in both adherent and polarized cells. The role of G and F actin
      isoforms was unveiled by the use of cytochalasin D, a cell-permeable fungal toxin
      that prevents F actin polymerization. Receptor-independent cytoskeleton
      remodeling by Cytochalasin D resulted in cell adhesion, polarization and
      intracellular accumulation of HIV virions similar to the effects gained with uPA.
      CONCLUSIONS: These findings illustrate the potential contribution of the uPA/uPAR
      system in the generation and/or maintenance of intra-cytoplasmic vesicles that
      actively accumulate virions, thus sustaining the presence of HIV reservoirs of
      macrophage origin. In addition, our observations also provide evidences that
      pathways controlling cytoskeleton remodeling and activation of PKCepsilon bear
      relevance for the design of new antiviral strategies aimed at interfering with
      the partitioning of virion budding between intra-cytoplasmic vesicles and plasma
      membrane in infected human macrophages.

PMID- 21858204
TI  - Nuttalliella namaqua: a living fossil and closest relative to the ancestral tick
      lineage: implications for the evolution of blood-feeding in ticks.
AB  - Ticks are monophyletic and composed of the hard (Ixodidae) and soft (Argasidae)
      tick families, as well as the Nuttalliellidae, a family with a single species,
      Nuttalliella namaqua. Significant biological differences in lifestyle strategies
      for hard and soft ticks suggest that various blood-feeding adaptations occurred
      after their divergence. The phylogenetic relationships between the tick families
      have not yet been resolved due to the lack of molecular data for N. namaqua. This
      tick possesses a pseudo-scutum and apical gnathostoma as observed for ixodids,
      has a leathery cuticle similar to argasids and has been considered the
      evolutionary missing link between the two families. Little knowledge exists with
      regard to its feeding biology or host preferences. Data on its biology and
      systematic relationship to the other tick families could therefore be crucial in
      understanding the evolution of blood-feeding behaviour in ticks. Live specimens
      were collected and blood meal analysis showed the presence of DNA for girdled
      lizards from the Cordylid family. Feeding of ticks on lizards showed that
      engorgement occurred rapidly, similar to argasids, but that blood meal
      concentration occurs via malpighian excretion of water. Phylogenetic analysis of
      the 18S nuclear and 16S mitochondrial genes indicate that N. namaqua grouped
      basal to the main tick families. The data supports the monophyly of all tick
      families and suggests the evolution of argasid-like blood-feeding behaviour in
      the ancestral tick lineage. Based on the data and considerations from literature
      we propose an origin for ticks in the Karoo basin of Gondwanaland during the late
      Permian. The nuttalliellid family almost became extinct during the End Permian
      event, leaving N. namaqua as the closest living relative to the ancestral tick
      lineage and the evolutionary missing link between the tick families.

PMID- 21858205
TI  - The pathologic effect of a novel neomorphic Fgf9(Y162C) allele is restricted to
      decreased vision and retarded lens growth.
AB  - Fibroblast growth factor (Fgf) signalling plays a crucial role in many
      developmental processes. Among the Fgf pathway ligands, Fgf9 (UniProt: P54130)
      has been demonstrated to participate in maturation of various organs and tissues
      including skeleton, testes, lung, heart, and eye. Here we establish a novel Fgf9
      allele, discovered in a dominant N-ethyl-N-nitrosourea (ENU) screen for eye-size
      abnormalities using the optical low coherence interferometry technique. The
      underlying mouse mutant line Aca12 was originally identified because of its
      significantly reduced lens thickness. Linkage studies located Aca12 to chromosome
      14 within a 3.6 Mb spanning interval containing the positional candidate genes
      Fgf9 (MGI: 104723), Gja3 (MGI: 95714), and Ift88 (MGI: 98715). While no sequence
      differences were found in Gja3 and Ift88, we identified an A->G missense mutation
      at cDNA position 770 of the Fgf9 gene leading to an Y162C amino acid exchange. In
      contrast to previously described Fgf9 mutants, Fgf9(Y162C) carriers were fully
      viable and did not reveal reduced body-size, male-to-female sexual reversal or
      skeletal malformations. The histological analysis of the retina as well as its
      basic functional characterization by electroretinography (ERG) did not show any
      abnormality. However, the analysis of head-tracking response of the Fgf9(Y162C)
      mutants in a virtual drum indicated a gene-dosage dependent vision loss of almost
      50%. The smaller lenses in Fgf9(Y162C) suggested a role of Fgf9 during lens
      development. Histological investigations showed that lens growth retardation
      starts during embryogenesis and continues after birth. Young Fgf9(Y162C) lenses
      remained transparent but developed age-related cataracts. Taken together,
      Fgf9(Y162C) is a novel neomorphic allele that initiates microphakia and reduced
      vision without effects on organs and tissues outside the eye. Our data point to a
      role of Fgf9 signalling in primary and secondary lens fiber cell growth. The
      results underline the importance of allelic series to fully understand multiple
      functions of a gene.

PMID- 21858207
TI  - A bioinformatics approach for determining sample identity from different lanes of
      high-throughput sequencing data.
AB  - The ability to generate whole genome data is rapidly becoming commoditized. For
      example, a mammalian sized genome (~3Gb) can now be sequenced using approximately
      ten lanes on an Illumina HiSeq 2000. Since lanes from different runs are often
      combined, verifying that each lane in a genome's build is from the same sample is
      an important quality control. We sought to address this issue in a post hoc
      bioinformatic manner, instead of using upstream sample or "barcode"
      modifications. We rely on the inherent small differences between any two
      individuals to show that genotype concordance rates can be effectively used to
      test if any two lanes of HiSeq 2000 data are from the same sample. As proof of
      principle, we use recent data from three different human samples generated on
      this platform. We show that the distributions of concordance rates are non
      overlapping when comparing lanes from the same sample versus lanes from different
      samples. Our method proves to be robust even when different numbers of reads are
      analyzed. Finally, we provide a straightforward method for determining the gender
      of any given sample. Our results suggest that examining the concordance of
      detected genotypes from lanes purported to be from the same sample is a
      relatively simple approach for confirming that combined lanes of data are of the
      same identity and quality.

PMID- 21858206
TI  - Bothrops jararaca peptide with anti-hypertensive action normalizes endothelium
      dysfunction involved in physiopathology of preeclampsia.
AB  - Preeclampsia, a pregnancy-specific syndrome characterized by hypertension,
      proteinuria and edema, is a major cause of fetal and maternal morbidity and
      mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide
      isolated from Bothrops jararaca venom, has been attributed with potent anti
      hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti
      hypertensive actions involved NO production in spontaneous hypertensive rats.
      Using in vitro studies we now show that Bj-PRO-10c was able to increase NO
      production in human umbilical vein endothelial cells from hypertensive pregnant
      women (HUVEC-PE) to levels observed in HUVEC of normotensive women. Moreover, in
      the presence of the peptide, eNOS expression as well as argininosuccinate
      synthase activity, the key rate-limiting enzyme of the citrulline-NO cycle, were
      enhanced. In addition, excessive superoxide production due to NO deficiency, one
      of the major deleterious effects of the disease, was inhibited by Bj-PRO-10c. Bj
      PRO-10c induced intracellular calcium fluxes in both, HUVEC-PE and HUVEC, which,
      however, led to activation of eNOS expression only in HUVEC-PE. Since Bj-PRO-10c
      promoted biological effects in HUVEC from patients suffering from the disorder
      and not in normotensive pregnant women, we hypothesize that Bj-PRO-10c induces
      its anti-hypertensive effect in mothers with preeclampsia. Such properties may
      initiate the development of novel therapeutics for treating preeclampsia.

PMID- 21858208
TI  - Newly developed Mg2+-selective fluorescent probe enables visualization of Mg2+
      dynamics in mitochondria.
AB  - Mg(2+) plays important roles in numerous cellular functions. Mitochondria take
      part in intracellular Mg(2+) regulation and the Mg(2+) concentration in
      mitochondria affects the synthesis of ATP. However, there are few methods to
      observe Mg(2+) in mitochondria in intact cells. Here, we have developed a novel
      Mg(2+)-selective fluorescent probe, KMG-301, that is functional in mitochondria.
      This probe changes its fluorescence properties solely depending on the Mg(2+)
      concentration in mitochondria under physiologically normal conditions.
      Simultaneous measurements using this probe together with a probe for cytosolic
      Mg(2+), KMG-104, enabled us to compare the dynamics of Mg(2+) in the cytosol and
      in mitochondria. With this method, carbonyl cyanide p-(trifluoromethoxy)
      phenylhydrazone (FCCP)-induced Mg(2+) mobilization from mitochondria to the
      cytosol was visualized. Although a FCCP-induced decrease in the Mg(2+)
      concentration in mitochondria and an increase in the cytosol were observed both
      in differentiated PC12 cells and in hippocampal neurons, the time-courses of
      concentration changes varied with cell type. Moreover, the relationship between
      mitochondrial Mg(2+) and Parkinson's disease was analyzed in a cellular model of
      Parkinson's disease by using the 1-methyl-4-phenylpyridinium ion (MPP(+)). A
      gradual decrease in the Mg(2+) concentration in mitochondria was observed in
      response to MPP(+) in differentiated PC12 cells. These results indicate that KMG
      301 is useful for investigating Mg(2+) dynamics in mitochondria. All animal
      procedures to obtain neurons from Wistar rats were approved by the ethical
      committee of Keio University (permit number is 09106-(1)).

PMID- 21858210
TI  - Plant identity influences decomposition through more than one mechanism.
AB  - Plant litter decomposition is a critical ecosystem process representing a major
      pathway for carbon flux, but little is known about how it is affected by changes
      in plant composition and diversity. Single plant functional groups (graminoids,
      legumes, non-leguminous forbs) were removed from a grassland in northern Canada
      to examine the impacts of functional group identity on decomposition. Removals
      were conducted within two different environmental contexts (fertilization and
      fungicide application) to examine the context-dependency of these identity
      effects. We examined two different mechanisms by which the loss of plant
      functional groups may impact decomposition: effects of the living plant community
      on the decomposition microenvironment, and changes in the species composition of
      the decomposing litter, as well as the interaction between these mechanisms. We
      show that the identity of the plant functional group removed affects
      decomposition through both mechanisms. Removal of both graminoids and forbs
      slowed decomposition through changes in the decomposition microenvironment. We
      found non-additive effects of litter mixing, with both the direction and identity
      of the functional group responsible depending on year; in 2004 graminoids
      positively influenced decomposition whereas in 2006 forbs negatively influenced
      decomposition rate. Although these two mechanisms act independently, their
      effects may be additive if both mechanisms are considered simultaneously. It is
      essential to understand the variety of mechanisms through which even a single
      ecosystem property is affected if we are to predict the future consequences of
      biodiversity loss.

PMID- 21858209
TI  - Genomic analysis of parent-of-origin allelic expression in Arabidopsis thaliana
      seeds.
AB  - Differential expression of maternally and paternally inherited alleles of a gene
      is referred to as gene imprinting, a form of epigenetic gene regulation common to
      flowering plants and mammals. In plants, imprinting primarily occurs in the
      endosperm, a seed tissue that supports the embryo during its growth and
      development. Previously, we demonstrated that widespread DNA demethylation at
      remnants of transposable elements accompanies endosperm development and that a
      subset of these methylation changes are associated with gene imprinting. Here we
      assay imprinted gene expression genome-wide by performing high-throughput
      sequencing of RNA derived from seeds of reciprocal intraspecific crosses. We
      identify more than 200 loci that exhibit parent-of-origin effects on gene
      expression in the endosperm, including a large number of transcription factors,
      hormone biosynthesis and response genes, and genes that encode regulators of
      epigenetic information, such as methylcytosine binding proteins, histone
      methyltransferases, and chromatin remodelers. The majority of these genes are
      partially, rather than completely, imprinted, suggesting that gene dosage
      regulation is an important aspect of imprinted gene expression.

PMID- 21858211
TI  - c-Myc regulates self-renewal in bronchoalveolar stem cells.
AB  - BACKGROUND: Bronchoalveolar stem cells (BASCs) located in the bronchoalveolar
      duct junction are thought to regenerate both bronchiolar and alveolar epithelium
      during homeostatic turnover and in response to injury. The mechanisms directing
      self-renewal in BASCs are poorly understood. METHODS: BASCs (Sca-1(+), CD34(+),
      CD31(-) and, CD45(-)) were isolated from adult mouse lung using FACS, and their
      capacity for self-renewal and differentiation were demonstrated by
      immunostaining. A transcription factor network of 53 genes required for
      pluripotency in embryonic stem cells was assessed in BASCs, Kras-initiated lung
      tumor tissue, and lung organogenesis by real-time PCR. c-Myc was knocked down in
      BASCs by infection with c-Myc shRNA lentivirus. Comprehensive miRNA and mRNA
      profiling for BASCs was performed, and significant miRNAs and mRNAs potentially
      regulated by c-Myc were identified. We explored a c-Myc regulatory network in
      BASCs using a number of statistical and computational approaches through two
      different strategies; 1) c-Myc/Max binding sites within individual gene
      promoters, and 2) miRNA-regulated target genes. RESULTS: c-Myc expression was
      upregulated in BASCs and downregulated over the time course of lung organogenesis
      in vivo. The depletion of c-Myc in BASCs resulted in decreased proliferation and
      cell death. Multiple mRNAs and miRNAs were dynamically regulated in c-Myc
      depleted BASCs. Among a total of 250 dynamically regulated genes in c-Myc
      depleted BASCs, 57 genes were identified as potential targets of miRNAs through
      miRBase and TargetScan-based computational mapping. A further 88 genes were
      identified as potential downstream targets through their c-Myc binding motif.
      CONCLUSION: c-Myc plays a critical role in maintaining the self-renewal capacity
      of lung bronchoalveolar stem cells through a combination of miRNA and
      transcription factor regulatory networks.

PMID- 21858213
TI  - Complex, dynamic combination of physical, chemical and nutritional variables
      controls spatio-temporal variation of sandy beach community structure.
AB  - Sandy beach ecological theory states that physical features of the beach control
      macrobenthic community structure on all but the most dissipative beaches.
      However, few studies have simultaneously evaluated the relative importance of
      physical, chemical and biological factors as potential explanatory variables for
      meso-scale spatio-temporal patterns of intertidal community structure in these
      systems. Here, we investigate macroinfaunal community structure of a micro-tidal
      sandy beach that is located on an oligotrophic subtropical coast and is
      influenced by seasonal estuarine input. We repeatedly sampled biological and
      environmental variables at a series of beach transects arranged at increasing
      distances from the estuary mouth. Sampling took place over a period of five
      months, corresponding with the transition between the dry and wet season. This
      allowed assessment of biological-physical relationships across chemical and
      nutritional gradients associated with a range of estuarine inputs. Physical,
      chemical, and biological response variables, as well as measures of community
      structure, showed significant spatio-temporal patterns. In general, bivariate
      relationships between biological and environmental variables were rare and weak.
      However, multivariate correlation approaches identified a variety of
      environmental variables (i.e., sampling session, the C?N ratio of particulate
      organic matter, dissolved inorganic nutrient concentrations, various size
      fractions of photopigment concentrations, salinity and, to a lesser extent, beach
      width and sediment kurtosis) that either alone or combined provided significant
      explanatory power for spatio-temporal patterns of macroinfaunal community
      structure. Overall, these results showed that the macrobenthic community on
      Mtunzini Beach was not structured primarily by physical factors, but instead by a
      complex and dynamic blend of nutritional, chemical and physical drivers. This
      emphasises the need to recognise ocean-exposed sandy beaches as functional
      ecosystems in their own right.

PMID- 21858212
TI  - Properties and crystal structure of methylenetetrahydrofolate reductase from
      Thermus thermophilus HB8.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes
      involved in homocysteine metabolism. Despite considerable genetic and clinical
      attention, the reaction mechanism and regulation of this enzyme are not fully
      understood because of difficult production and poor stability. While recombinant
      enzymes from thermophilic organisms are often stable and easy to prepare,
      properties of thermostable MTHFRs have not yet been reported.
      METHODOLOGY/PRINCIPAL FINDINGS: MTHFR from Thermus thermophilus HB8, a homologue
      of Escherichia coli MetF, has been expressed in E. coli and purified. The
      purified MTHFR was chiefly obtained as a heterodimer of apo- and holo-subunits,
      that is, one flavin adenine dinucleotide (FAD) prosthetic group bound per dimer.
      The crystal structure of the holo-subunit was quite similar to the
      beta(8)alpha(8) barrel of E. coli MTHFR, while that of the apo-subunit was a
      previously unobserved closed form. In addition, the intersubunit interface of the
      dimer in the crystals was different from any of the subunit interfaces of the
      tetramer of E. coli MTHFR. Free FAD could be incorporated into the apo-subunit of
      the purified Thermus enzyme after purification, forming a homodimer of holo
      subunits. Comparison of the crystal structures of the heterodimer and the
      homodimer revealed different intersubunit interfaces, indicating a large
      conformational change upon FAD binding. Most of the biochemical properties of the
      heterodimer and the homodimer were the same, except that the homodimer showed
      ~50% activity per FAD-bound subunit in folate-dependent reactions.
      CONCLUSIONS/SIGNIFICANCE: The different intersubunit interfaces and rearrangement
      of subunits of Thermus MTHFR may be related to human enzyme properties, such as
      the allosteric regulation by S-adenosylmethionine and the enhanced instability of
      the Ala222Val mutant upon loss of FAD. Whereas E. coli MTHFR was the only
      structural model for human MTHFR to date, our findings suggest that Thermus MTHFR
      will be another useful model for this important enzyme.

PMID- 21858214
TI  - GPR50 interacts with TIP60 to modulate glucocorticoid receptor signalling.
AB  - GPR50 is an orphan G-protein coupled receptor most closely related to the
      melatonin receptors. The physiological function of GPR50 remains unclear,
      although our previous studies implicate the receptor in energy homeostasis. Here,
      we reveal a role for GPR50 as a signalling partner and modulator of the
      transcriptional co-activator TIP60. This interaction was identified in a yeast
      two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of
      TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear
      localisation of full length GPR50, and resulted in nuclear translocation of the
      cytoplasmic tail of the receptor, suggesting a functional interaction of the two
      proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of
      glucocorticoid receptor (GR) signalling. In line with in vitro results,
      repression of pituitary Pomc expression, and induction of gluconeogenic genes in
      liver in response to the GR agonist, dexamethasone was attenuated in Gpr50(-/-)
      mice. These results identify a novel role for GPR50 in glucocorticoid receptor
      signalling through interaction with TIP60.

PMID- 21858215
TI  - Systematic spatial bias in DNA microarray hybridization is caused by probe spot
      position-dependent variability in lateral diffusion.
AB  - BACKGROUND: The hybridization of nucleic acid targets with surface-immobilized
      probes is a widely used assay for the parallel detection of multiple targets in
      medical and biological research. Despite its widespread application, DNA
      microarray technology still suffers from several biases and lack of
      reproducibility, stemming in part from an incomplete understanding of the
      processes governing surface hybridization. In particular, non-random spatial
      variations within individual microarray hybridizations are often observed, but
      the mechanisms underpinning this positional bias remain incompletely explained.
      METHODOLOGY/PRINCIPAL FINDINGS: This study identifies and rationalizes a
      systematic spatial bias in the intensity of surface hybridization, characterized
      by markedly increased signal intensity of spots located at the boundaries of the
      spotted areas of the microarray slide. Combining observations from a simplified
      single-probe block array format with predictions from a mathematical model, the
      mechanism responsible for this bias is found to be a position-dependent variation
      in lateral diffusion of target molecules. Numerical simulations reveal a strong
      influence of microarray well geometry on the spatial bias. CONCLUSIONS:
      Reciprocal adjustment of the size of the microarray hybridization chamber to the
      area of surface-bound probes is a simple and effective measure to minimize or
      eliminate the diffusion-based bias, resulting in increased uniformity and
      accuracy of quantitative DNA microarray hybridization.

PMID- 21858216
TI  - Acquisition of glial cells missing 2 enhancers contributes to a diversity of
      ionocytes in zebrafish.
AB  - Glial cells missing 2 (gcm2) encoding a GCM-motif transcription factor is
      expressed in the parathyroid in amniotes. In contrast, gcm2 is expressed in
      pharyngeal pouches (a homologous site of the parathyroid), gills, and H(+)-ATPase
      rich cells (HRCs), a subset of ionocytes on the skin surface of the teleost fish
      zebrafish. Ionocytes are specialized cells that are involved in osmotic
      homeostasis in aquatic vertebrates. Here, we showed that gcm2 is essential for
      the development of HRCs and Na(+)-Cl(-) co-transporter-rich cells (NCCCs),
      another subset of ionocytes in zebrafish. We also identified gcm2 enhancer
      regions that control gcm2 expression in ionocytes of zebrafish. Comparisons of
      the gcm2 locus with its neighboring regions revealed no conserved elements
      between zebrafish and tetrapods. Furthermore, We observed gcm2 expression
      patterns in embryos of the teleost fishes Medaka (Oryzias latipes) and fugu (Fugu
      niphobles), the extant primitive ray-finned fishes Polypterus (Polypterus
      senegalus) and sturgeon (a hybrid of Huso huso * Acipenser ruhenus), and the
      amphibian Xenopus (Xenopus laevis). Although gcm2-expressing cells were observed
      on the skin surface of Medaka and fugu, they were not found in Polypterus,
      sturgeon, or Xenopus. Our results suggest that an acquisition of enhancers for
      the expression of gcm2 contributes to a diversity of ionocytes in zebrafish
      during evolution.

PMID- 21858217
TI  - Dopaminergic and serotonergic drug use: a nationwide register-based study of over
      1,300,000 older people.
AB  - OBJECTIVE: To investigate the use of dopaminergic and serotonergic drugs in
      elderly people. METHODS: We analyzed data on age, sex and dispensed drugs for
      individuals aged >=65 years registered in the Swedish Prescribed Drug Register
      from July to September 2008 (n = 1,347,564; 81% of the total population aged >=65
      years in Sweden). Main outcome measures were dopaminergic (enhancing and/or
      lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of
      these. RESULTS: Dopaminergic and serotonergic drugs were used by 5.6% and 13.2%
      the participants, respectively. Female gender was related to use of both
      dopaminergic and, particularly, serotonergic drugs. Higher age was associated
      with use of dopamine lowering drugs and serotonergic drugs, whereas the
      association with use of dopamine enhancing drugs declined in the oldest old. The
      occurrence of combinations of dopaminergic and serotonergic drugs was generally
      low, with dopamine lowering + serotonin lowering drug the most common combination
      (1.6%). Female gender was associated with all of the combinations of dopaminergic
      and serotonergic drugs, whereas age showed a mixed pattern. CONCLUSION:
      Approximately one out of ten older patients uses serotonergic drugs and one out
      of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic
      drugs in the elderly patients is a potential problem due to the fact that aging
      is associated with a down-regulation of both these monoaminergic systems. Future
      studies are needed for evaluation of the impact of these drugs on different
      cognitive and emotional functions in old age.

PMID- 21858218
TI  - PTTG1 attenuates drug-induced cellular senescence.
AB  - As PTTG1 (pituitary tumor transforming gene) abundance correlates with adverse
      outcomes in cancer treatment, we determined mechanisms underlying this
      observation by assessing the role of PTTG1 in regulating cell response to anti
      neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1(-/-)) exhibited enhanced
      drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis,
      mitosis catastrophe or DNA damage were not detected, but features of senescence
      were observed using low doses of doxorubicin and TSA. The number of drug-induced
      PTTG1(-/-) senescent cells increased ~4 fold as compared to WT PTTG1-replete
      cells (p<0.001). p21, an important regulator of cell senescence, was induced ~3
      fold in HCT116 PTTG1(-/-) cells upon doxorubicin or Trichostatin A treatment.
      Binding of Sp1, p53 and p300 to the p21 promoter was enhanced in PTTG1(-/-) cells
      after treatment, suggesting transcriptional regulation of p21. p21 knock down
      abrogated the observed senescent effects of these drugs, indicating that PTTG1
      likely suppresses p21 to regulate drug-induced senescence. PTTG1 also regulated
      SW620 colon cancer cells response to doxorubicin and TSA mediated by p21.
      Subcutaneously xenografted PTTG1(-/-) HCT116 cells developed smaller tumors and
      exhibited enhanced responses to doxorubicin. PTTG1(-/-) tumor tissue derived from
      excised tumors exhibited increased doxorubicin-induced senescence. As senescence
      is a determinant of cell responses to anti-neoplastic treatments, these findings
      suggest PTTG1 as a tumor cell marker to predict anti-neoplastic treatment
      outcomes.

PMID- 21858219
TI  - Identification of a novel ZIC3 isoform and mutation screening in patients with
      heterotaxy and congenital heart disease.
AB  - Patients with heterotaxy have characteristic cardiovascular malformations,
      abnormal arrangement of their visceral organs, and midline patterning defects
      that result from abnormal left-right patterning during embryogenesis. Loss of
      function of the transcription factor ZIC3 causes X-linked heterotaxy and isolated
      congenital heart malformations and represents one of the few known monogenic
      causes of congenital heart disease. The birth incidence of heterotaxy-spectrum
      malformations is significantly higher in males, but our previous work indicated
      that mutations within ZIC3 did not account for the male over-representation.
      Therefore, cross species comparative sequence alignment was used to identify a
      putative novel fourth exon, and the existence of a novel alternatively spliced
      transcript was confirmed by amplification from murine embryonic RNA and
      subsequent sequencing. This transcript, termed Zic3-B, encompasses exons 1, 2,
      and 4 whereas Zic3-A encompasses exons 1, 2, and 3. The resulting protein
      isoforms are 466 and 456 amino acid residues respectively, sharing the first 407
      residues. Importantly, the last two amino acids in the fifth zinc finger DNA
      binding domain are altered in the Zic3-B isoform, indicating a potential
      functional difference that was further evaluated by expression, subcellular
      localization, and transactivation analyses. The temporo-spatial expression
      pattern of Zic3-B overlaps with Zic3-A in vivo, and both isoforms are localized
      to the nucleus in vitro. Both isoforms can transcriptionally activate a Gli
      binding site reporter, but only ZIC3-A synergistically activates upon co
      transfection with Gli3, suggesting that the isoforms are functionally distinct.
      Screening 109 familial and sporadic male heterotaxy cases did not identify
      pathogenic mutations in the newly identified fourth exon and larger studies are
      necessary to establish the importance of the novel isoform in human disease.

PMID- 21858220
TI  - Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38
      activation in intestine: the versatile adjuvant for gefitinib therapy.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) patients with L858R or exon 19
      deletion mutations in epidermal growth factor receptor (EGFR) have good responses
      to the tyrosine kinase inhibitor (TKI), gefitinib. However, patients with wild
      type EGFR and acquired mutation in EGFR T790M are resistant to gefitinib
      treatment. Here, we showed that curcumin can improve the efficiency of gefitinib
      in the resistant NSCLC cells both in vitro and in vivo models. METHODS/PRINCIPAL
      FINDINGS: After screening 598 herbal and natural compounds, we found curcumin
      could inhibit cell proliferation in different gefitinib-resistant NSCLC cell
      lines; concentration-dependently down-regulate EGFR phosphorylation through
      promoting EGFR degradation in NSCLC cell lines with wild-type EGFR or T790M EGFR.
      In addition, the anti-tumor activity of gefitinib was potentiated via curcumin
      through blocking EGFR activation and inducing apoptosis in gefitinib-resistant
      NSCLC cell lines; also the combined treatment with curcumin and gefitinib
      exhibited significant inhibition in the CL1-5, A549 and H1975 xenografts tumor
      growth in SCID mice through reducing EGFR, c-MET, cyclin D1 expression, and
      inducing apoptosis activation through caspases-8, 9 and PARP. Interestingly, we
      observed that the combined treatment group represented better survival rate and
      less intestinal mucosal damage compare to gefitinib-alone therapy. We showed that
      curcumin attenuated the gefitinib-induced cell proliferation inhibition and
      apoptosis through altering p38 mitogen-activated protein kinase (MAPK) activation
      in intestinal epithelia cell. CONCLUSIONS/SIGNIFICANCE: Curcumin potentiates
      antitumor activity of gefitinib in cell lines and xenograft mice model of NSCLC
      through inhibition of proliferation, EGFR phosphorylation, and induction EGFR
      ubiquitination and apoptosis. In addition, curcumin attenuates gefitinib-induced
      gastrointestinal adverse effects via altering p38 activation. These findings
      provide a novel treatment strategy that curcumin as an adjuvant to increase the
      spectrum of the usage of gefitinib and overcome the gefitinib inefficiency in
      NSCLC patients.

PMID- 21858221
TI  - One-step preservation of phosphoproteins and tissue morphology at room
      temperature for diagnostic and research specimens.
AB  - BACKGROUND: There is an urgent need to measure phosphorylated cell signaling
      proteins in cancer tissue for the individualization of molecular targeted kinase
      inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue
      procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most
      clinics and compromises diagnostic morphology. Formalin fixation preserves tissue
      histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing
      phosphoproteins. We originated and evaluated a novel one-step biomarker and
      histology preservative (BHP) chemistry that stabilizes signaling protein
      phosphorylation and retains formalin-like tissue histomorphology with equivalent
      immunohistochemistry in a single paraffin block. RESULTS: Total protein yield
      extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared
      to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to
      be stable over extended fixation times in BHP fixed paraffin embedded human colon
      mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally
      preserved in mouse liver, while AMPKbeta1 Ser108 was slightly elevated after BHP
      fixation. More than 25 tissues from mouse, cat and human specimens were evaluated
      for preservation of histomorphology. Selected tissues were evaluated in a multi
      site, independent pathology review. Tissue fixed with BHP showed equivalent
      preservation of cytoplasmic and membrane cytomorphology, with significantly
      better nuclear chromatin preservation by BHP compared to formalin.
      Immunohistochemical staining of 13 non-phosphorylated proteins, including
      estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or
      stronger in BHP compared to formalin. BHP demonstrated significantly improved
      immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3
      alpha/beta Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA
      Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the
      phosphorylation state of several signaling proteins at a level comparable to snap
      freezing, while maintaining the full diagnostic immunohistochemical and
      histomorphologic detail of formalin fixation. This new tissue fixative has the
      potential to greatly facilitate personalized medicine, biobanking, and phospho
      proteomic research.

PMID- 21858222
TI  - Diffuse and specific tectopulvinar terminals in the tree shrew: synapses,
      synapsins, and synaptic potentials.
AB  - The pulvinar nucleus of the tree shrew receives both topographic (specific) and
      nontopographic (diffuse) projections from superior colliculus (SC), which form
      distinct synaptic arrangements. We characterized the physiological properties of
      these synapses and describe two distinct types of excitatory postsynaptic
      potentials (EPSPs) that correlate with structural properties of the specific and
      diffuse terminals. Synapses formed by specific terminals were found to be
      significantly longer than those formed by diffuse terminals. Stimulation of these
      two terminal types elicited two types of EPSPs that differed in their latency and
      threshold amplitudes. In addition, in response to repetitive stimulation (0.5-20
      Hz) one type of EPSP displayed frequency-dependent depression whereas the
      amplitudes of the second type of EPSP were not changed by repetitive stimulation
      of up to 20 Hz. To relate these features to vesicle release, we compared the
      synapsin content of terminals in the pulvinar nucleus and the dorsal lateral
      geniculate (dLGN) by combining immunohistochemical staining for synapsin I or II
      with staining for the type 1 or type 2 vesicular glutamate transporters (markers
      for corticothalamic and tectothalamic/retinogeniculate terminals, respectively).
      We found that retinogeniculate terminals do not contain either synapsin I or
      synapsin II, corticothalamic terminals in the dLGN and pulvinar contain synapsin
      I, but not synapsin II, whereas tectopulvinar terminals contain both synapsin I
      and synapsin II. Finally, both types of EPSPs showed a graded increase in
      amplitude with increasing stimulation intensity, suggesting convergence; this was
      confirmed using a combination of anterograde tract tracing and
      immunocytochemistry. We suggest that the convergent synaptic arrangements, as
      well as the unique synapsin content of tectopulvinar terminals, allow them to
      relay a dynamic range of visual signals from the SC.

PMID- 21858223
TI  - Aberrant activation of ERK/FOXM1 signaling cascade triggers the cell
      migration/invasion in ovarian cancer cells.
AB  - Forkhead box M1 (FOXM1) is a proliferation-associated transcription factor
      essential for cell cycle progression. Numerous studies have documented that FOXM1
      has multiple functions in tumorigenesis and its elevated levels are frequently
      associated with cancer progression. Here, we characterized the role of ERK/FOXM1
      signaling in mediating the metastatic potential of ovarian cancer cells.
      Immunohistochemical (IHC), immunoblotting and semi-quantitative RT-PCR analyses
      found that both phospho-ERK and FOXM1 were frequently upregulated in ovarian
      cancers. Intriguingly, the overexpressed phospho-ERK (p<0.001) and FOXM1
      (p<0.001) were significantly correlated to high-grade ovarian tumors with
      aggressive behavior such as metastasized lymph node (5 out of 6). Moreover, the
      expressions of phospho-ERK and FOXM1 had significantly positive correlation
      (p<0.001). Functionally, ectopic expression of FOXM1B remarkably enhanced cell
      migration/invasion, while FOXM1C not only increased cell proliferation but also
      promoted cell migration/invasion. Conversely, inhibition of FOXM1 expression by
      either thiostrepton or U0126 could significantly impair FOXM1 mediated oncogenic
      capacities. However, the down-regulation of FOXM1 by either thiostrepton or U0126
      required the presence of p53 in ovarian cancer cells. Collectively, our data
      suggest that over-expression of FOXM1 might stem from the constitutively active
      ERK which confers the metastatic capabilities to ovarian cancer cells. The
      impairment of metastatic potential of cancer cells by FOXM1 inhibitors
      underscores its therapeutic value in advanced ovarian tumors.

PMID- 21858224
TI  - Importance of suitable reference gene selection for quantitative real-time PCR:
      special reference to mouse myocardial infarction studies.
AB  - BACKGROUND: Quantitative real-time PCR (qPCR) is a widely used technique for gene
      expression analysis. Its reliability is highly dependent upon selection of the
      appropriate reference genes for accurate gene expression normalization. In this
      study, we investigated the expression stability of 10 commonly used reference
      genes in a mouse myocardial infarction model. METHODS & RESULTS: The expression
      stability of the 10 reference genes (Actb, B2m, Eef1a1, Gapdh, Hprt, Polr2a,
      Ppia, Rpl13a, Tbp, Tpt1) was analyzed using the geNorm software. Overall, the
      combination of Hprt, Rpl13a and Tpt1 was the most stable reference gene set in
      our experiments. Gapdh, Polr2a and Actb consistently showed the highest gene
      expression variability and the expression levels of Gapdh, Polr2a, Actb, B2m and
      Eef1a1 were found to be selectively up- or downregulated after myocardial
      infarction. We normalized the expression of Nppb and Vcam1, using different
      reference gene strategies and demonstrated that their induction after myocardial
      infarction was most clearly revealed with the optimal reference gene combination.
      However, the use of suboptimal reference gene combinations resulted in
      detrimental effects on gene expression levels and variability with a gradual loss
      of the expression differences and a significant reduction in statistical power.
      CONCLUSIONS: Hprt, Rpl13a and Tpt1 are a set of stably expressed reference genes
      for accurate gene expression normalization in myocardial infarction studies in
      mice. We found that Gapdh, Polr2a and Actb display high expression variability in
      mouse myocardial infarction tissues and that loss of statistical power and
      increase in sample size are the evident consequences of choosing suboptimal
      combinations of reference genes. We furthermore caution against the use of Gapdh,
      Polr2a, Actb, B2m and Eef1a1 for gene expression normalization in myocardial
      infarction studies because of selective up- or downregulation after myocardial
      infarction, which could potentially lead to biased study outcomes.

PMID- 21858225
TI  - Same/different concept learning by capuchin monkeys in matching-to-sample tasks.
AB  - The ability to understand similarities and analogies is a fundamental aspect of
      human advanced cognition. Although subject of considerable research in
      comparative cognition, the extent to which nonhuman species are capable of
      analogical reasoning is still debated. This study examined the conditions under
      which tufted capuchin monkeys (Cebus apella) acquire a same/different concept in
      a matching-to-sample task on the basis of relational similarity among multi-item
      stimuli. We evaluated (i) the ability of five capuchin monkeys to learn the
      same/different concept on the basis of the number of items composing the stimuli
      and (ii) the ability to match novel stimuli after training with both several
      small stimulus sets and a large stimulus set. We found the first evidence of
      same/different relational matching-to-sample abilities in a New World monkey and
      demonstrated that the ability to match novel stimuli is within the capacity of
      this species. Therefore, analogical reasoning can emerge in monkeys under
      specific training conditions.

PMID- 21858226
TI  - Regulation of anthrax toxin-specific antibody titers by natural killer T cell
      derived IL-4 and IFNgamma.
AB  - Activation of Natural Killer-like T cells (NKT) with the CD1d ligand alpha-GC
      leads to enhanced production of anthrax toxin protective Ag (PA)-neutralizing
      Abs, yet the underlying mechanism for this adjuvant effect is not known. In the
      current study we examined the role of Th1 and Th2 type responses in NKT-mediated
      enhancement of antibody responses to PA. First, the contribution of IL-4 and
      IFNgamma to the production of PA-specific toxin-neutralizing Abs was examined. By
      immunizing C57Bl/6 controls IL-4(-/-) mice and IFNgamma(-/-) mice and performing
      passive serum transfer experiments, it was observed that sera containing PA
      specific IgG1, IgG2b and IgG2c neutralized toxin in vitro and conferred
      protection in vivo. Sera containing IgG2b and IgG2c neutralized toxin in vitro
      but were not sufficient for protection in vivo. Sera containing IgG1 and IgG2b
      neutralized toxin in vitro and conferred protection in vivo. IgG1 therefore
      emerged as a good correlate of protection. Next, C57Bl/6 mice were immunized with
      PA alone or PA plus a Th2-skewing alpha-GC derivative known as OCH. Neutralizing
      PA-specific IgG1 responses were modestly enhanced by OCH in C57Bl/6 mice.
      Conversely, IgG2b and IgG2c were considerably enhanced in PA/OCH-immunized IL-4(
      /-) mice but did not confer protection. Finally, bone marrow chimeras were
      generated such that NKT cells were unable to express IL-4 or IFNgamma. NKT
      derived IL-4 was required for OCH-enhanced primary IgG1 responses but not recall
      responses. NKT-derived IL-4 and IFNgamma also influenced primary and recall IgG2b
      and IgG2c titers. These data suggest targeted skewing of the Th2 response by
      alpha-GC derivatives can be exploited to optimize anthrax vaccination.

PMID- 21858227
TI  - The thyroid hormone receptors modulate the skin response to retinoids.
AB  - BACKGROUND: Retinoids play an important role in skin homeostasis and when
      administered topically cause skin hyperplasia, abnormal epidermal differentiation
      and inflammation. Thyroidal status in humans also influences skin morphology and
      function and we have recently shown that the thyroid hormone receptors (TRs) are
      required for a normal proliferative response to 12-O-tetradecanolyphorbol-13
      acetate (TPA) in mice. METHODOLOGY/PRINCIPAL FINDINGS: We have compared the
      epidermal response of mice lacking the thyroid hormone receptor binding isoforms
      TRalpha1 and TRbeta to retinoids and TPA. Reduced hyperplasia and a decreased
      number of proliferating cells in the basal layer in response to 9-cis-RA and TPA
      were found in the epidermis of TR-deficient mice. Nuclear levels of proteins
      important for cell proliferation were altered, and expression of keratins 5 and 6
      was also reduced, concomitantly with the decreased number of epidermal cell
      layers. In control mice the retinoid (but not TPA) induced parakeratosis and
      diminished expression of keratin 10 and loricrin, markers of early and terminal
      epidermal differentiation, respectively. This reduction was more accentuated in
      the TR deficient animals, whereas they did not present parakeratosis. Therefore,
      TRs modulate both the proliferative response to retinoids and their inhibitory
      effects on skin differentiation. Reduced proliferation, which was reversed upon
      thyroxine treatment, was also found in hypothyroid mice, demonstrating that
      thyroid hormone binding to TRs is required for the normal response to retinoids.
      In addition, the mRNA levels of the pro-inflammatory cytokines TNFalpha and IL-6
      and the chemotactic proteins S1008A and S1008B were significantly elevated in the
      skin of TR knock-out mice after TPA or 9-cis-RA treatment and immune cell
      infiltration was also enhanced. CONCLUSIONS/SIGNIFICANCE: Since retinoids are
      commonly used for the treatment of skin disorders, these results demonstrating
      that TRs regulate skin proliferation, differentiation and inflammation in
      response to these compounds could have not only physiological but also
      therapeutic implications.

PMID- 21858228
TI  - Murine polyomavirus virus-like particles carrying full-length human PSA protect
      BALB/c mice from outgrowth of a PSA expressing tumor.
AB  - Virus-like particles (VLPs) consist of capsid proteins from viruses and have been
      shown to be usable as carriers of protein and peptide antigens for immune
      therapy. In this study, we have produced and assayed murine polyomavirus (MPyV)
      VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for
      their potential use for immune therapy in a mouse model system. BALB/c mice
      immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a
      PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with
      adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs).
      Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to
      efficiently protect mice from tumor outgrowth. In addition, cellular and humoral
      immune responses after immunization were examined. PSA-specific CD4(+) and CD8(+)
      cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs
      loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies
      than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c
      mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an
      efficient PSA-specific tumor protective immune response, including both CD4(+)
      and CD8(+) cells with a low induction of anti-VLP antibodies.

PMID- 21858229
TI  - The hepatitis C virus E1 glycoprotein undergoes productive folding but
      accelerated degradation when expressed as an individual subunit in CHO cells.
AB  - Hepatitis C Virus E1E2 heterodimers are components of the viral spike. Although
      there is a general agreement on the necessity of the co-expression of both E1 and
      E2 on a single coding unit for their productive folding and assembly, in a
      previous study using an in vitro system we obtained strong indications that E1
      can achieve folding in absence of E2. Here, we have studied the folding pathway
      of unescorted E1 from stably expressing CHO cells, compared to the folding
      observed in presence of the E2 protein. A DTT-resistant conformation is achieved
      by E1 in both situations, consistent with the presence of an E2-independent
      oxidative pathway. However, while the E1E2 heterodimer is stable inside cells, E1
      expressed alone is degraded within a few hours. On the other hand, the oxidation
      and stability of individually expressed E2 subunits is dependent on E1 co
      expression. These data are consistent with E1 and E2 assisting each other for
      correct folding via different mechanisms: E2 assists E1 by stabilizing a semi
      native conformation meanwhile E1 drives E2 towards a productive folding pathway.

PMID- 21858230
TI  - Implicating calpain in tau-mediated toxicity in vivo.
AB  - Alzheimer's disease and other related neurodegenerative disorders known as
      tauopathies are characterized by the accumulation of abnormally phosphorylated
      and aggregated forms of the microtubule-associated protein tau. Several
      laboratories have identified a 17 kD proteolytic fragment of tau in degenerating
      neurons and in numerous cell culture models that is generated by calpain cleavage
      and speculated to contribute to tau toxicity. In the current study, we employed a
      Drosophila tauopathy model to investigate the importance of calpain-mediated tau
      proteolysis in contributing to tau neurotoxicity in an animal model of human
      neurodegenerative disease. We found that mutations that disrupted endogenous
      calpainA or calpainB activity in transgenic flies suppressed tau toxicity.
      Expression of a calpain-resistant form of tau in Drosophila revealed that
      mutating the putative calpain cleavage sites that produce the 17 kD fragment was
      sufficient to abrogate tau toxicity in vivo. Furthermore, we found significant
      toxicity in the fly retina associated with expression of only the 17 kD tau
      fragment. Collectively, our data implicate calpain-mediated proteolysis of tau as
      an important pathway mediating tau neurotoxicity in vivo.

PMID- 21858231
TI  - Plasmodium falciparum metacaspase PfMCA-1 triggers a z-VAD-fmk inhibitable
      protease to promote cell death.
AB  - Activation of proteolytic cell death pathways may circumvent drug resistance in
      deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this
      end, it is important to define the cell death pathway(s) in parasites and thus
      characterize proteases such as metacaspases (MCA), which have been reported to
      induce cell death in plants and Leishmania parasites. We, therefore, investigated
      whether the cell death function of MCA is conserved in different protozoan
      parasite species such as Plasmodium falciparum and Leishmania major, focusing on
      the substrate specificity and functional role in cell survival as compared to
      Saccharomyces cerevisae. Our results show that, similarly to Leishmania,
      Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity
      and its expression in yeast induced growth inhibition as well as an 82% increase
      in cell death under oxidative stress, a situation encountered by parasites during
      the host or when exposed to drugs such as artemisins. Furthermore, we show that
      MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk
      inhibitable protease. Our data provide evidence that MCA from both Leishmania and
      Plasmodium falciparum is able to induce cell death in stress conditions, where it
      specifically activates a downstream enzyme as part of a cell death pathway. This
      enzymatic activity is also induced by the antimalarial drug chloroquine in
      erythrocytic stages of Plasmodium falciparum. Interestingly, we found that
      blocking parasite cell death influences their drug sensitivity, a result which
      could be used to create therapeutic strategies that by-pass drug resistance
      mechanisms by acting directly on the innate pathways of protozoan cell death.

PMID- 21858232
TI  - Matrin 3 binds and stabilizes mRNA.
AB  - Matrin 3 (MATR3) is a highly conserved, inner nuclear matrix protein with two
      zinc finger domains and two RNA recognition motifs (RRM), whose function is
      largely unknown. Recently we found MATR3 to be phosphorylated by the protein
      kinase ATM, which activates the cellular response to double strand breaks in the
      DNA. Here, we show that MATR3 interacts in an RNA-dependent manner with several
      proteins with established roles in RNA processing, and maintains its interaction
      with RNA via its RRM2 domain. Deep sequencing of the bound RNA (RIP-seq)
      identified several small noncoding RNA species. Using microarray analysis to
      explore MATR3's role in transcription, we identified 77 transcripts whose amounts
      depended on the presence of MATR3. We validated this finding with nine
      transcripts which were also bound to the MATR3 complex. Finally, we demonstrated
      the importance of MATR3 for maintaining the stability of several of these mRNA
      species and conclude that it has a role in mRNA stabilization. The data suggest
      that the cellular level of MATR3, known to be highly regulated, modulates the
      stability of a group of gene transcripts.

PMID- 21858236
TI  - Postepidemic analysis of Rift Valley fever virus transmission in northeastern
      kenya: a village cohort study.
AB  - BACKGROUND: In endemic areas, Rift Valley fever virus (RVFV) is a significant
      threat to both human and animal health. Goals of this study were to measure human
      anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift
      Valley Fever (RVF) epidemic, to identify risk factors for interval
      seroconversion, and to monitor individuals previously exposed to RVFV in order to
      document the persistence of their anti-RVFV antibodies. METHODOLOGY/FINDINGS: We
      conducted a village cohort study in Ijara District, Northeastern Province, Kenya.
      One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF
      outbreak were restudied to determine interval anti-RVFV seroconversion and
      persistence of humoral immunity since 2006. Ninety-two additional subjects were
      enrolled from randomly selected households to help identify risk factors for
      current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local
      residents were RVFV seropositive. 1/85 at-risk individuals restudied in the
      follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%
      39%) of newly tested individuals were seropositive. All 13 individuals with
      positive titers (by plaque reduction neutralization testing (PRNT80) in 2006
      remained positive in 2009. After adjustment in multivariable logistic models,
      age, village, and drinking raw milk were significantly associated with RVFV
      seropositivity. Visual impairment (defined as <= 20/80) was much more likely in
      the RVFV-seropositive group (P<0.0001). CONCLUSIONS: Our results highlight
      significant variability in RVFV exposure in two neighboring villages having very
      similar climate, terrain, and insect density. Among those with previous exposure,
      RVFV titers remained at > 1?40 for more than 3 years. In concordance with
      previous studies, residents of the more rural village were more likely to be
      seropositive and RVFV seropositivity was associated with poor visual acuity. Raw
      milk consumption was strongly associated with RVFV exposure, which may represent
      an important new focus for public health education during future RVF outbreaks.

PMID- 21858237
TI  - Cryptic diversity within the major trypanosomiasis vector Glossina fuscipes
      revealed by molecular markers.
AB  - BACKGROUND: The tsetse fly Glossina fuscipes s.l. is responsible for the
      transmission of approximately 90% of cases of human African trypanosomiasis (HAT)
      or sleeping sickness. Three G. fuscipes subspecies have been described, primarily
      based upon subtle differences in the morphology of their genitalia. Here we
      describe a study conducted across the range of this important vector to determine
      whether molecular evidence generated from nuclear DNA (microsatellites and gene
      sequence information), mitochondrial DNA and symbiont DNA support the existence
      of these taxa as discrete taxonomic units. PRINCIPAL FINDINGS: The nuclear
      ribosomal Internal transcribed spacer 1 (ITS1) provided support for the three
      subspecies. However nuclear and mitochondrial sequence data did not support the
      monophyly of the morphological subspecies G. f. fuscipes or G. f. quanzensis.
      Instead, the most strongly supported monophyletic group was comprised of flies
      sampled from Ethiopia. Maternally inherited loci (mtDNA and symbiont) also
      suggested monophyly of a group from Lake Victoria basin and Tanzania, but this
      group was not supported by nuclear loci, suggesting different histories of these
      markers. Microsatellite data confirmed strong structuring across the range of G.
      fuscipes s.l., and was useful for deriving the interrelationship of closely
      related populations. CONCLUSION/SIGNIFICANCE: We propose that the morphological
      classification alone is not used to classify populations of G. fuscipes for
      control purposes. The Ethiopian population, which is scheduled to be the target
      of a sterile insect release (SIT) programme, was notably discrete. From a
      programmatic perspective this may be both positive, given that it may reflect
      limited migration into the area or negative if the high levels of differentiation
      are also reflected in reproductive isolation between this population and the
      flies to be used in the release programme.

PMID- 21858238
TI  - Chagasic thymic atrophy does not affect negative selection but results in the
      export of activated CD4+CD8+ T cells in severe forms of human disease.
AB  - Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some
      pathophysiological conditions, including infectious diseases. In the murine model
      of Chagas disease, it has been shown that the protozoan parasite Trypanosoma
      cruzi is able to target the thymus and induce alterations of the thymic
      microenvironment and the lymphoid compartment. In the acute phase, this results
      in a severe atrophy of the organ and early release of DP cells into the
      periphery. To date, the effect of the changes promoted by the parasite infection
      on thymic central tolerance has remained elusive. Herein we show that the
      intrathymic key elements that are necessary to promote the negative selection of
      thymocytes undergoing maturation during the thymopoiesis remains functional
      during the acute chagasic thymic atrophy. Intrathymic expression of the
      autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is
      normal. In addition, the expression of the proapoptotic Bim protein in thymocytes
      was not changed, revealing that the parasite infection-induced thymus atrophy has
      no effect on these marker genes necessary to promote clonal deletion of T cells.
      In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic
      system, the administration of OVA peptide into infected mice with thymic atrophy
      promoted OVA-specific thymocyte apoptosis, further indicating normal negative
      selection process during the infection. Yet, although the intrathymic checkpoints
      necessary for thymic negative selection are present in the acute phase of Chagas
      disease, we found that the DP cells released into the periphery acquire an
      activated phenotype similar to what is described for activated effector or memory
      single-positive T cells. Most interestingly, we also demonstrate that increased
      percentages of peripheral blood subset of DP cells exhibiting an activated HLA
      DR+ phenotype are associated with severe cardiac forms of human chronic Chagas
      disease. These cells may contribute to the immunopathological events seen in the
      Chagas disease.

PMID- 21858239
TI  - CD4+CD25+ regulatory cells contribute to the regulation of colonic Th2
      granulomatous pathology caused by schistosome infection.
AB  - Eggs of the helminth Schistosoma mansoni accumulate in the colon following
      infection and generate Th2-biassed inflammatory granulomas which become down-
      modulated in size as the infection proceeds to chronicity. However, although
      CD4+CD25+FoxP3+ regulatory T cells (T(regs)) are known to suppress Th1-mediated
      colitis, it is not clear whether they control Th2-associated pathologies of the
      large intestine which characterise several helminth infections. Here we used a
      novel 3D-multiphoton confocal microscopy approach to visualise and quantify
      changes in the size and composition of colonic granulomas at the acute and
      chronic phases of S. mansoni infection. We observed decreased granuloma size, as
      well as reductions in the abundance of DsRed+ T cells and collagen deposition at
      14 weeks (chronic) compared to 8 weeks (acute) post-infection. Th2 cytokine
      production (i.e. IL-4, IL-5) in the colonic tissue and draining mesenteric lymph
      node (mLN) decreased during the chronic phase of infection, whilst levels of TGF
      beta1 increased, co-incident with reduced mLN proliferative responses, granuloma
      size and fibrosis. The proportion of CD4+CD25+FoxP3+T(regs): CD4+ cells in the
      mLN increased during chronic disease, while within colonic granulomas there was
      an approximate 4-fold increase. The proportion of CD4+CD25+FoxP3+T(regs) in the
      mLN that were CD103+ and CCR5+ also increased indicating an enhanced potential to
      home to intestinal sites. CD4+CD25+ cells suppressed antigen-specific Th2 mLN
      cell proliferation in vitro, while their removal during chronic disease resulted
      in significantly larger granulomas, partial reversal of Th2 hypo-responsiveness
      and an increase in the number of eosinophils in colonic granulomas. Finally,
      transfer of schistosome infection-expanded CD4+CD25+T(regs) down-modulated the
      development of colonic granulomas, including collagen deposition. Therefore,
      CD4+CD25+FoxP3+T(regs) appear to control Th2 colonic granulomas during chronic
      infection, and are likely to play a role in containing pathology during
      intestinal schistosomiasis.

PMID- 21858241
TI  - Restricted application of insecticides: a promising tsetse control technique, but
      what do the farmers think of it?
AB  - BACKGROUND: Restricted application of insecticides to cattle is a cheap and safe
      farmer-based method to control tsetse. In Western Africa, it is applied using a
      footbath, mainly to control nagana and the tick Amblyomma variegatum. In Eastern
      and Southern Africa, it might help controlling the human disease, i.e., Rhodesian
      sleeping sickness as well. The efficiency of this new control method against
      ticks, tsetse and trypanosomoses has been demonstrated earlier. The invention, co
      built by researchers and farmers ten years ago, became an innovation in Burkina
      Faso through its diffusion by two development projects. METHODOLOGY/PRINCIPAL
      FINDINGS: In this research, we studied the process and level of adoption in 72
      farmers inhabiting the peri-urban areas of Ouagadougou and Bobo-Dioulasso.
      Variables describing the livestock farming system, the implementation and
      perception of the method and the knowledge of the epidemiological system were
      used to discriminate three clusters of cattle farmers that were then compared
      using indicators of adoption. The first cluster corresponded to modern farmers
      who adopted the technique very well. The more traditional farmers were
      discriminated into two clusters, one of which showed a good adoption rate,
      whereas the second failed to adopt the method. The economic benefit and the
      farmers' knowledge of the epidemiological system appeared to have a low impact on
      the early adoption process whereas some modern practices, as well as social
      factors appeared critical. The quality of technical support provided to the
      farmers had also a great influence. Cattle farmers' innovation-risk appraisal was
      analyzed using Rogers' adoption criteria which highlighted individual variations
      in risk perceptions and benefits, as well as the prominent role of the socio
      technical network of cattle farmers. CONCLUSIONS/SIGNIFICANCE: Results are
      discussed to highlight the factors that should be taken into consideration, to
      move discoveries from bench to field for an improved control of trypanosomoses
      vectors.

PMID- 21858240
TI  - A replicating cytomegalovirus-based vaccine encoding a single Ebola virus
      nucleoprotein CTL epitope confers protection against Ebola virus.
AB  - BACKGROUND: Human outbreaks of Ebola virus (EBOV) are a serious human health
      concern in Central Africa. Great apes (gorillas/chimpanzees) are an important
      source of EBOV transmission to humans due to increased hunting of wildlife
      including the 'bush-meat' trade. Cytomegalovirus (CMV) is an highly immunogenic
      virus that has shown recent utility as a vaccine platform. CMV-based vaccines
      also have the unique potential to re-infect and disseminate through target
      populations regardless of prior CMV immunity, which may be ideal for achieving
      high vaccine coverage in inaccessible populations such as great apes.
      METHODOLOGY/PRINCIPAL FINDINGS: We hypothesize that a vaccine strategy using CMV
      based vectors expressing EBOV antigens may be ideally suited for use in
      inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV
      based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing
      a CD8+ T cell epitope from the nucleoprotein (NP) of Zaire ebolavirus (ZEBOV)
      (MCMV/ZEBOV-NP(CTL)). MCMV/ZEBOV-NP(CTL) induced high levels of long-lasting (>8
      months) CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated
      animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV
      antibodies were only sporadically detected in vaccinated animals prior to ZEBOV
      challenge suggesting a role, at least in part, for T cells in protection.
      CONCLUSIONS/SIGNIFICANCE: This study demonstrates the ability of a CMV-based
      vaccine approach to protect against an highly virulent human pathogen, and
      supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent
      EBOV transmission in wildlife populations.

PMID- 21858242
TI  - Inflammatory cytokine expression is associated with chikungunya virus resolution
      and symptom severity.
AB  - The Chikungunya virus infection zones have now quickly spread from Africa to
      parts of Asia, North America and Europe. Originally thought to trigger a disease
      of only mild symptoms, recently Chikungunya virus caused large-scale fatalities
      and widespread economic loss that was linked to recent virus genetic mutation and
      evolution. Due to the paucity of information on Chikungunya immunological
      progression, we investigated the serum levels of 13 cytokines/chemokines during
      the acute phase of Chikungunya disease and 6- and 12-month post-infection follow
      up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL
      6 and CXCL10/IP-10 were significantly raised in the acute phase compared to
      follow-up samples. Furthermore, IL-1beta, TNF-alpha, Il-12, IL-10, IFN-gamma and
      IL-5 had low initial acute phase levels that significantly increased at later
      time points. Analysis of symptom severity showed association with CXCL9/MIG,
      CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease
      establishment and subsequent convalescence, which is imperative to the treatment
      and containment of this quickly evolving and frequently re-emerging disease.

PMID- 21858243
TI  - Prevalence and factors associated with Leishmania infantum infection of dogs from
      an urban area of Brazil as identified by molecular methods.
AB  - BACKGROUND: Various factors contribute to the urbanization of the visceral
      leishmaniasis (VL), including the difficulties of implementing control measures
      relating to the domestic reservoir. The aim of this study was to determine the
      prevalence of canine visceral leishmaniasis in an urban endemic area in Brazil
      and the factors associated with Leishmania infantum infection among seronegative
      and PCR-positive dogs. METHODOLOGY: A cross-sectional study was conducted in Belo
      Horizonte, Minas Gerais, Brazil. Blood samples were collected from 1,443 dogs.
      Serology was carried out by using two enzyme-linked immunosorbent assays
      (Biomanguinhos/FIOCRUZ/RJ and "in house"), and molecular methods were developed,
      including PCR-RFLP. To identify the factors associated with early stages of
      infection, only seronegative (n = 1,213) animals were evaluated. These animals
      were divided into two groups: PCR-positive (n = 296) and PCR-negative (n = 917)
      for L. infantum DNA. A comparison of these two groups of dogs taking into
      consideration the characteristics of the animals and their owners was performed.
      A mixed logistic regression model was used to identify factors associated with L.
      infantum infection. PRINCIPAL FINDINGS: Of the 1,443 dogs examined, 230 (15.9%)
      were seropositive in at least one ELISA, whereas PCR-RFLP revealed that 356
      animals (24.7%) were positive for L. infantum DNA. Results indicated that the
      associated factors with infection were family income<twice the Brazilian minimum
      salary (OR 2.3; 95%CI 1.4-3.8), knowledge of the owner regarding the vector (OR
      1.9; 95%CI 1.1-3.4), the dog staying predominantly in the backyard (OR 2.2; 95%CI
      1.1-4.1), and a lack of previous serological examination for VL (OR 1.5; 95%CI
      1.1-2.3). CONCLUSIONS: PCR detected a high prevalence of L. infantum infection in
      dogs in an area under the Control Program of VL intervention. Socioeconomic
      variables, dog behavior and the knowledge of the owner regarding the vector were
      factors associated with canine visceral leishmaniasis (CVL). The absence of
      previous serological examination conducted by the control program was also
      associated with L. infantum infection. It is necessary to identify the risk
      factors associated with CVL to understand the expansion and urbanization of VL.

PMID- 21858244
TI  - Truncated (N)-Methanocarba Nucleosides as A(1) Adenosine Receptor Agonists and
      Partial Agonists: Overcoming Lack of a Recognition Element.
AB  - A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and
      anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR
      were truncated to eliminate 5'-CH(2)OH. This modification previously converted
      A(3)AR agonists into antagonists, but the comparable effect at A(1)AR is unknown.
      In comparison to ribosides, affinity at the A(1)AR was less well preserved than
      at the A(3)AR, although a few derivatives were moderately A(1)AR selective,
      notably full agonist 21 (N(6)-dicyclopropylmethyl, K(i) 47.9 nM). Thus, at the
      A(1)AR recognition elements for nucleoside binding depend more on 5'region
      interactions, and in their absence A(3)AR selectivity predominates. Based on the
      recently reported agonist-bound AR structure, this difference between subtypes
      likely correlates with an essential His residue in transmembrane domain 6 of A(1)
      but not A(3)AR. The derivatives ranged from partial to full agonists in A(1)AR
      mediated adenylate cyclase inhibition. Truncated derivatives have more drug-like
      physical properties than other A(1)AR agonists; this approach is appealing for
      preclinical development.

PMID- 21858247
TI  - Emerging Risk Stratification in Syncope.

PMID- 21858245
TI  - Therapeutic potential of c-Myc inhibition in the treatment of hypertrophic
      cardiomyopathy.
AB  - Investigating the pathophysiological importance of the molecular and mechanical
      development of cardiomyopathy is critical to find new and broader means of
      protection against this disease that is increasing in prevalence and impact. The
      current available treatment options for cardiomyopathy mainly focus on treating
      symptoms and strive to make the patient more comfortable while preventing
      progression of disease and sudden death. The proto-oncogene c-Myc (Myc) has been
      shown to be increased in many different types of heart disease, including
      hypertrophic cardiomyopathy, before any signs of the disease are present. As the
      mechanisms of action and multiple pathways of dependent actions of Myc are being
      dissected by many research groups, inhibition of Myc is becoming an attractive
      paradigm for prevention and treatment of cardiomyopathy and heart failure.
      Elucidating the role Myc plays in the development, propagation and perpetuation
      of cardiomyopathy and heart failure will one day translate into potential
      therapeutics for cardiomyopathy.

PMID- 21858248
TI  - Malign Asystole During Head-up Tilt Test: A Case Report and Overview.

PMID- 21858246
TI  - Polymeric vectors for ocular gene delivery.
AB  - Gene therapy holds promise for the treatment of many inherited and acquired
      diseases of the eye. Successful ocular gene therapy interventions depend on
      efficient gene transfer to targeted cells with minimal toxicity. A major
      challenge is to overcome both intracellular and extracellular barriers associated
      with ocular gene delivery. Numerous viral and nonviral vectors were explored to
      improve transfection efficiency. Among nonviral delivery systems, polymeric
      vectors have gained significant attention in recent years owing to their nontoxic
      and non-immunogenic nature. Polyplexes or nanoparticles can be prepared by
      interaction of cationic polymers with DNA, which facilitate cellular uptake,
      endolysosomal escape and nuclear entry through active mechanisms. Chemical
      modification of these polymers allows for the generation of flexible delivery
      vectors with desirable properties. In this article several synthetic and natural
      polymeric systems utilized for ocular gene delivery are discussed.

PMID- 21858249
TI  - The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization
      by commercial and specific coral snake antivenoms.
AB  - The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick
      biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The
      venom (0.5-50MUg/ml) caused irreversible, time- and concentration-dependent
      blockade, with BC being more sensitive than PND (50% blockade with 10MUg/ml in
      22+/-;3min and 62+/-4min, respectively; mean+/-SEM, n=6; p<0.05). In BC
      preparations, venom (0.5MUg/ml) progressively abolished ACh-induced contractures,
      whereas contractures to exogenous KCl and muscle twitches in curarized
      preparations were unaffected. The venom neither altered creatine kinase release
      (venom: 25.8+/-1.75IU/l vs control: 24.3+/-2.2IU/l, n=6, after 120min), nor it
      caused significant muscle damage (50MUg of venom/ml vs control: 3.5+/-0.8% vs
      1.1+/-0.7% for PND; 4.3+/-1.5% vs 1.2+/-0.5% for BC, n=5). The venom had low
      PLA(2) activity. Neurotoxicity was effectively neutralized by commercial Micrurus
      antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus
      venom acts postsynaptically on nicotinic receptors, with no significant
      myotoxicity.

PMID- 21858250
TI  - Hidden Danger: Spatial neglect can complicate recovery after stroke.

PMID- 21858251
TI  - Statistical validation of a global model for the distribution of the ultimate
      number of citations accrued by papers published in a scientific journal.
AB  - A central issue in evaluative bibliometrics is the characterization of the
      citation distribution of papers in the scientific literature. Here, we perform a
      large-scale empirical analysis of journals from every field in Thomson Reuters'
      Web of Science database. We find that only 30 of the 2,184 journals have citation
      distributions that are inconsistent with a discrete lognormal distribution at the
      rejection threshold that controls the False Discovery Rate at 0.05. We find that
      large, multidisciplinary journals are over-represented in this set of 30
      journals, leading us to conclude that, within a discipline, citation
      distributions are lognormal. Our results strongly suggest that the discrete
      lognormal distribution is a globally accurate model for the distribution of
      "eventual impact" of scientific papers published in single-discipline journal in
      a single year that is removed sufficiently from the present date.

PMID- 21858252
TI  - A 20 gene model for predicting nodal involvement in bladder cancer patients with
      muscle invasive tumors.
AB  - Bladder cancer is the fourth most common cancer in males worldwide and also the
      most expensive cancer to treat. Approximately 25% of patients with muscle
      invasive disease are found to harbor occult lymph node involvement at the time of
      cystectomy and this finding is associated with a 5-year survival rate of <30%. If
      these patients could be identified pre-operatively, use of neoadjuvant
      chemotherapy may be advantageous because this approach has been shown to confer a
      small survival advantage in patients with muscle invasive disease. However,
      because only a few patients benefit from this approach it has not been used
      extensively in the United States with fewer than 2% of patients undergoing this
      treatment. This is largely due to concerns that since neoadjuvant therapy is
      beneficial for only a few patients, it has the potential to delay surgery in the
      majority who do not benefit. However, since neoadjuvant therapy is most likely to
      benefit those patients at highest risk for progression of disease, it follows
      that patients with lymph node metastases would constitute an ideal group for such
      treatment. Hence, if patients with occult node involvement prior to cystectomy
      could be identified, they would constitute an ideal group for application of
      neoadjuvant therapy as they are most likely to benefit. In this summary, we
      describe the first multi-analyte gene expression model developed for predicting
      occult nodal involvement at cystectomy in bladder cancer patients, for the
      purpose of making better informed decisions regarding neoadjuvant therapy. The 20
      gene model, which was developed on Affymetrix Human Genome U133A and U133 Plus
      2.0 arrays, identified individuals with high relative risk (RR) of nodal
      involvement (RR = 1.74, 95% CI, 1.03 - 2.93) intermediate risk (RR = 1.05, 95%
      CI, .45 - 2.41), and low risk (RR = 0.74, 95% CI, 0.51 - 0.96), when evaluated in
      an independent test dataset. The 20 gene model can be applied to formalin-fixed
      paraffin embedded tissue with sufficient tumor content, making implementation in
      routine diagnostic tissue highly feasible. Although a clinical assay for the gene
      panel has not undergone analytic validation in a clinical laboratory setting,
      multiple platforms are available which could be utilized for routine testing,
      including real-time reverse transcriptase PCR directed against individual
      analytes as well as microarray approaches.

PMID- 21858253
TI  - Identification of Influenza Cases During the H1N1 Pandemic in Massachusetts Using
      Population-Based Hospital Discharge Data.
AB  - Objectives(1) To characterize the epidemiology of H1N1-related hospitalizations
      in Massachusetts; and (2) to compare characteristics of those hospitalized during
      periods of seasonal influenza activity and during the H1N1 pandemic.
      MethodsAuthors applied maximum and minimum criteria to the Massachusetts Hospital
      Discharge Database to identify H1N1-related hospitalizations. They constructed
      annual line graphs describing mean frequencies of influenza-like illness(ILI)
      related discharges between 2005-2008, and compared these rates to early waves of
      H1N1 in 2009. ResultsDuring spring and summer 2009, there were significantly
      higher rates of ILI-related hospital discharges in Massachusetts compared to 2005
      2008. Out of 359,344 total discharges between April 26-September 30,2009, H1N1
      related hospitalizations ranged from 601 to 10,967 cases. Minimum criteria
      confirmed that H1N1 affected a younger population (50% were <18 years), with
      higher rates among African-Americans (18%) and Hispanics (23%) and higher rates
      of ICU admission (21%) compared to seasonal influenza (39%, 10%, 14%, and 17%
      respectively). ConclusionsThis is the first population-based assessment of
      epidemiological characteristics of hospitalized H1N1 cases in Massachusetts, and
      it is the first to include all possible hospitalized cases in the analysis. The
      authors confirm that large administrative data sets can detect hospitalizations
      for influenza during a pandemic, but estimated case counts vary widely depending
      on selection criteria used. Maximum criteria overestimated H1N1 activity, and
      those meeting minimum criteria resemble published accounts of H1N1-related
      hospitalizations closely.

PMID- 21858254
TI  - The nose, snoring and obstructive sleep apnoea.
AB  - Snoring and obstructive sleep apnoea are both due to multilevel anatomical
      obstruction, and the nose and nasal pathology both contribute in many cases. This
      paper addresses some of the issues surrounding the problem and briefly discusses
      the role of medication and nasal dilators and in more detail the implication of
      nasal surgery in various aspects of sleep related breathing disorders (SRBD).
      Nasal obstruction leads to mouth breathing, which destabilises the upper airway
      and aggravates SRBD.

PMID- 21858255
TI  - Therapeutic Index (TIX) for intranasal corticosteroids in the treatment of
      allergic rhinitis.
AB  - BACKGROUND: Intranasal corticosteroids (INS) are the first line treatment for
      allergic rhinitis (AR). To guide clinical decision-making, we created a
      therapeutic index (TIX) for INS reflecting efficacy and safety. METHODS: A
      Medline search (1966 to June 2009) was carried out to identify all placebo
      controlled randomized trials, and observational reports for safety issues, with
      Dexamethasone, Budesonide (BUD), Fluticasone propionate (FP), Fluticasone furoate
      (FF), Flunisolide, Mometasone furoate (MF), Triamcinolone (TRIAM), and
      Beclomethasone dipropionate (BDP) as treatment for AR. Data on three efficacy
      (nasal symptoms, ocular symptoms, global assessment) and three safety outcomes
      (epistaxis, growth, systemic ocular effects) were extracted. Meta analyses were
      performed for each INS and outcome and results were categorised into scores by
      quartiles. Scores of the three efficacy and safety outcomes were summed up to
      create summation scores for efficacy (ES) and side effects (AES), respectively
      with a maximum of 9 points. The TIX was then defined as the ratio of ES and AES.
      RESULTS: Data of 84 studies were extracted. Based on availability of data, a TIX
      was calculated for 6 substances. BUD showed the highest efficacy score followed
      by MF and TRIAM. The lowest scores for side effects were achieved by MF and TRIAM
      followed by FP. These findings resulted in TIX scores of 7 and 5 for MF and
      TRIAM, respectively, indicating a high efficacy and low potential of adverse
      events. Medium scores were reached by BUD and FP and lower scores by BDP and FF.
      CONCLUSION: Although safety and efficacy is proven for all available INS by
      multiple studies, the systematic aggregation and analysis of data allows for a
      differentiated summary on clinically important features.

PMID- 21858256
TI  - Study of microbial spread when using multiple-use nasal anaesthetic spray.
AB  - BACKGROUND: Current economic constraints have led to the emergence of reusable
      anaesthetic sprays with replacement nozzles (Xylocaine) as an alternative to
      disposable anaesthetic solutions (Co-phenylcaine) for rhinological procedures.
      The former costs 213.84 per year vers12,047.69 for the latter, at equivocal
      doses. However, research regarding the sterility of such instruments is limited.
      The aim of this in vitro study was to determine whether bottles of Xylocaine
      could pose a risk of cross-infection to patients. METHODS: Two techniques were
      used. The first was to introduce nozzles into methylene blue and fluorescein
      dyes, and then analysing the anaesthetic solutions using spectrophotometry for
      assessment of colour change indicating retrograde contamination. The second
      method involved spraying Xylocaine into cultures of Staphylococcus aureus with
      concurrent nozzle changes. This was repeated over a 36-day-period. Sterility
      checks were performed on the Xylocaine before and after inoculation into the
      culture. RESULTS: None of the anaesthetic solutions showed the presence of dyed
      saline following spectrophotometric analysis. No S. aureus was isolated from any
      of the 30 spray bottles cultures over the 36-day trial period. CONCLUSION: It was
      demonstrated that using the Xylocaine spray with disposable nozzles for each
      patient should not pose a cross infection risk to patients.

PMID- 21858257
TI  - Nasally inhaled pulsating aerosols: lung, sinus and nose deposition.
AB  - OBJECTIVES: Topical delivery of drugs to the sinuses is challenging and requires
      also particular administration manoeuvres from the patient. This study was
      conducted to investigate 1) the delivery efficiency of a pulsating aerosol
      (Vibrent prototype device) to the sinuses and the nose, 2) the aerosol fraction
      that will deposit in the lungs and 3) potential differences regarding sinus and
      nasal deposition ratio when comparing aerosol administration during two different
      administration routes. METHODS: An open label deposition study in healthy
      volunteers was conducted using 99mTc-DTPA radiolabeled pulsating aerosols in
      comparison to nasal pump sprays. Deposition and retention of pulsating aerosols
      was assessed by gamma camera imaging during spontaneous nasal breathing and
      during closed soft palate administration. RESULTS: Aerosol administration during
      nasal breathing vs. application with closed soft plate results in significant
      lung, nasal and sinus deposition. No significant differences were observed for
      nasal clearance. In comparison, drug delivery using nasal pump sprays resulted in
      non-significant sinus, 100 % nasal and non-significant lung deposition. The
      clearance kinetics after nasal pump spray delivery was significantly accelerated.
      DISCUSSION: The standard application mode of pulsation aerosols with closed soft
      palate results in negligible lung deposition and therefore limits drug delivery
      to the nasal cavity only, minimizing unwanted side effects. Administration during
      spontaneous nasal breathing shows only 10% lung deposition, which is tolerable
      during drug administration. Relevant paranasal sinus deposition is noted during
      both application modes and clearance kinetics remains essentially unchanged. In
      contrast, nasal pump sprays do not show sinus drug delivery and nasal drug
      residence time is shortened. CONCLUSION: Pulsating aerosols offer advantageous
      topical nasal and sinus drug delivery options.

PMID- 21858258
TI  - Visual analogue scale assessment of nasal obstruction might define patients
      candidates to spirometry.
AB  - BACKGROUND: Asthma may be frequently associated with allergic rhinitis. Bronchial
      obstruction is a characteristic of asthma and spirometry is a cardinal step in
      asthma diagnosis. However, spirometry is rarely suitable in medical office.
      Visual Analogue Scales (VAS) is frequently used in common practice. OBJECTIVE:
      This study aimed at evaluating the suitability of the use of VAS assessment of
      nasal obstruction to define patients with allergic rhinitis candidates for
      spirometry. METHODS: 1728 patients with allergic rhinitis were consecutively
      evaluated. Clinical examination, skin prick test, VAS assessment, and spirometry
      were performed in all patients. RESULTS: 7.9% of patients had impaired FEV1
      values and 24.5% had impaired FEF25-75 values. A VAS value < 3.3 might identify
      with good reliability patients with impaired FEF25-75 values, such as having
      initial bronchial airflow limitation. CONCLUSIONS: This study, performed in a
      large cohort of subjects, highlights the close link between upper and lower
      airways and shows the possible suitability of the use of nasal obstruction VAS
      assessment to define patients with allergic rhinitis candidates for spirometry.

PMID- 21858259
TI  - The value of bilateral simultaneous nasal spirometry in the assessment of
      patients undergoing septoplasty.
AB  - PROBLEM: There is no consensus regarding the best approach to select patients for
      septoplasty. Patient dissatisfaction after septoplasty implies that clinical
      examination alone is inadequate to detect a clinically relevant nasal septal
      deviation (NSD). Objective testing provides an in-depth analysis of nasal
      obstruction and its underlying anatomic causes but it is effort consuming,
      requires training and it is not widely available. AIM: We studied the role of
      bilateral simultaneous nasal spirometry (BSNS) in the preoperative selection of
      patients for septoplasty. PATIENTS, SUBJECTS AND METHODS: Thirty patients with
      nasal obstruction and NSD were assessed by subjective measures and BSNS before
      and after septoplasty. The decongested nasal partitioning ratio (NPR) was used as
      a measure of the degree of NSD. Thirty healthy controls were recruited for
      providing a normal range of NPR values. RESULTS: All patients were subjectively
      improved after septoplasty but only those with NPR out of the normal limits had a
      significant reduction of NPR. Patients with unilateral symptoms and NPR beyond
      normal limits were also able to identify the more obstructed side preoperatively.
      For this group of patients, physicians were able to identify the convex side of
      NSD preoperatively. No correlation between subjective measures of nasal
      obstruction or airflow asymmetry and NPR was observed. CONCLUSION: BSNS is a
      rapid, easily interpretable, noninvasive technique, which identifies patients
      with large NSDs who, irrespective of concomitant mucosal factors of nasal
      obstruction, warrant septoplasty. BSNS is not applicable in cases with a septal
      perforation or an S type septal deviation, it cannot detect an insufficient nasal
      valve and it does not substitute rhinomanometry or acoustic rhinometry.

PMID- 21858260
TI  - Reference values for peak nasal inspiratory flow in children and adolescents in
      Brazil.
AB  - STATEMENT OF THE PROBLEM: Allergic rhinitis is a global public health issue. Peak
      nasal inspiratory flow (PNIF) can help in the assessment of patients with
      allergic rhinitis. However, reference values in the literature for PNIF in school
      children and adolescents are limited. THE AIM OF THIS STUDY was to identify
      reference values of PNIF among children and adolescents. METHODS: We conducted a
      cross-sectional study to identify reference values of PNIF among healthy school
      children and adolescents aged from eight to fifteen years old, selected from 14
      randomly selected public schools. Participants performed measurements of PNIF
      using the In-check-inspiratory flow meter (Clement Clarke, Harlow, England). PNIF
      values were correlated to gender, age, height, weight and body mass index.
      RESULTS: A total of 526 subjects participated in the study. The final linear
      regression model for PNIF allowed obtaining the following equation for subjects
      aged from eight to 15 years old: PNIF (l/m) = height (centimeters) x 0.7 + 11.2,
      for boys and PNIF (l/m) = height (centimeters) x 0.7, for girls. CONCLUSION: the
      equations of the final regression model resulted in a simple formula to obtain
      reference values of PNIF for subjects aged from 8 to 15 years old.

PMID- 21858261
TI  - Characteristics and risk factors of mucosal cysts in the paranasal sinuses.
AB  - BACKGROUND: Though mucosal cysts in the paranasal sinuses (PSMCs) are common
      findings on radiographic images, the nature of PSMCs and risk factors for the
      development of PSMCs have not yet been determined. The aim of this study was to
      evaluate the characteristics of PSMCs using brain magnetic resonance (MR)
      imaging. METHODOLOGY/PRINCIPAL: A total of 6831 subjects who underwent health
      checkup including brain MR imaging were included in this study. The
      characteristics of PSMCs, including their location, number and size, as well as
      the presence of obstruction of the sinus ostium and sinusitis, were analysed
      using brain MR images. Structured questionnaires and medical records were
      reviewed to evaluate the smoking status and comorbid medical conditions. RESULTS:
      The overall prevalence of PSMCs was 7.4% and was significantly higher in females
      than in males. PSMCs were most commonly found in the maxillary sinus, most of
      which were located unilaterally as a solitary cyst. Large cysts were associated
      with obstruction of the sinus ostium and subsequent sinusitis. Smoking was a
      single important risk factor for developing PSMCs. No significant associations
      were found between symptoms (nasal/respiratory) and the presence of PSMCs.
      CONCLUSIONS: The prevalence of PSMCs was 7.4% and decreased with age. Large cysts
      may lead to obstruction of the sinus and subsequent sinusitis. Smoking was an
      important risk factor for PSMCs, and the total amount of smoking correlated with
      cyst size. Most subjects were asymptomatic, and specific treatment was not
      performed.

PMID- 21858262
TI  - Spontaneous silent sinus syndrome (imploding antrum syndrome): case series of 16
      patients.
AB  - INTRODUCTION: Silent sinus syndrome (SSS) is a rare idiopathic collapse of the
      maxillary sinus and orbital floor. We present the second largest series of
      sixteen patients with SSS and describe their management. METHODS: A cohort of 16
      patients with spontaneous SSS between 1999 and 2009 were reviewed at the Royal
      National Throat Nose and Ear Hospital. All patients were initially referred from
      a postgraduate ophthalmic hospital, Moorfields Hospital. RESULTS: Fourteen
      patients required endoscopic sinus surgery to re-establish maxillary sinus
      drainage and the remaining two settled with intranasal medical therapy consisting
      of steroids and decongestions. Follow- up ranged from 6 months to 4 years with a
      mean of 2.6 years. An improvement in enophthalmos and was seen in all surgically
      treated patients with a mean improvement of 2.2mm and range 0.5-4mm. DISCUSSION:
      SSS arises from congestion of the ostiomeatal complex resulting in negative
      pressure within the maxillary sinus and a gradual implosion of the antral cavity.
      Endoscopic sinus surgery successfully re-establishes maxillary aeration in our
      series and leads to clinical and aesthetic improvement in the degree of
      enophthalmos and has avoided the need for orbital floor repair in all but two
      cases.

PMID- 21858263
TI  - Allergic fungal rhinosinusitis - a new staging system.
AB  - BACKGROUND: The existing Kupferberg post-operative endoscopic staging system for
      allergic fungal rhinosinusitis (AFRS) has 4 stages (0-3) based on the 'global'
      appearance of one side of the nose. Patients may however show visual improvement
      and yet remain at the same stage due to persistence in one sinus cavity, thus
      making the staging system ineffective. The aim of this study was to validate a
      new system that allows greater sensitivity in characterising the inflammation
      seen endoscopically. METHODOLOGY: A series of endoscopy videos of 50 patients
      with AFRS were retrospectively staged using a new ten-grade system, scoring each
      sinus cavity (maxillary, ethmoid, frontal and sphenoid) from 0-9 for increasing
      mucosal oedema and 1 point for the presence of fungal mucin giving a maximum
      score of 40 for each side of the nose. To assess reliability, 4 independent
      rhinologists were also asked to score the videos using the new system. RESULTS: A
      greater variety in the spectrum of mucosal disease was demonstrated with the new
      system allowing for a more descriptive analysis of its severity and its response,
      or lack of, to treatment. The inter-class correlation between the 6 total
      observers was 0.86 (95% CI: 0.83, 0.92). CONCLUSION: Use of the new staging
      system provides a more sensitive tool for following patients' progress post
      operatively in allergic fungal rhinosinusitis and in determining their response
      to treatment.

PMID- 21858265
TI  - Correlation analyses of detection thresholds of four different odorants.
AB  - The detection threshold task of the Sniffin' Sticks can be conducted using two
      different odorants - n-butanol or phenylethyl alcohol (PEA). Previous studies
      show contradictory results regarding the correlation analysis of the two
      odorants. The current study investigated the relationship between PEA and n
      butanol with respect to previous findings and subject population. We compared
      four different odorants (PEA, n-butanol, isoamyl butyrate, isobutanol) in an
      olfactory detection threshold task depending on subject population. Test odorants
      were applied to 73 healthy subjects. The experiment was divided into two sessions
      performed on two different days. The correlation coefficient between individual
      thresholds of PEA and n-butanol was not significant when exclusively normosmic
      subjects were included, but significant when additionally hyposmic, older
      subjects were studied. Comparable results were found for the analysis of the
      odorants n-butanol and isoamyl butyrate. Correlation between n-butanol and
      isobutanol was significant, both for exclusively normosmic, and additionally
      older, hyposmic subjects. The analyses of all other odorants revealed no
      significant correlations. Results give explanations for previous contradictory
      findings regarding investigations of PEA and n-butanol in a detection threshold
      task, and indicate that a formal validation of the Sniffin' Sticks with PEA as
      odorant is required.

PMID- 21858264
TI  - Gustatory and olfactory dysfunction in older adults: a national probability
      study.
AB  - BACKGROUND: Olfactory and gustatory functions have not been well characterized in
      older adults in the US. Consequently, their relationships to sociodemographic
      characteristics, as well as physical and mental health, were studied in a large
      national probability sample using brief validated tests of chemosensory function.
      METHODS: A five-odour identification test and taste-impregnated strips of filter
      paper (sweet, sour, bitter, and salty) assessed the ability to identify
      chemosensory stimuli. RESULTS: Severe gustatory dysfunction was more prevalent
      than severe olfactory dysfunction. Age, education and sex were independently
      associated with performance on both the olfactory and gustatory identification
      tasks. Higher scores were associated with female sex, higher level of education,
      and lower age. Odour identification scores exhibited a positive, albeit weak,
      correlation with BMI, and food-related odours were better identified than non
      food odours. In addition, odour identification performance was also negatively
      associated with depressive symptoms. CONCLUSIONS: These data demonstrate a high
      prevalence of severe gustatory and, to a somewhat lesser extent, olfactory
      dysfunction in a population-based sample and demonstrate that even brief tests
      are capable of detecting correlations between both chemical senses and relevant
      health measures outside a clinical setting.

PMID- 21858266
TI  - Factors affecting the impact of olfactory loss on the quality of life and
      emotional coping ability.
AB  - BACKGROUND: Olfactory impaired patients have decreased quality of life and may
      need to develop a coping ability for the olfactory loss. This study investigated
      how factors like olfactory function, disease duration, etiology, age, and gender
      affect patients' quality of life and emotional ability to cope. METHODS: Four
      hundred and thirteen consecutive patients with the chief complaint of olfactory
      dysfunction were evaluated. The Questionnaire of Olfactory Disorders (QOD)
      included negative statements (QOD-NS) that indicated the impact on the quality of
      life, and positive statements (QOD-PS) reflecting the emotional coping ability.
      Relations between studied factors and QOD-NS or QOD-PS were analyzed. RESULTS:
      Poorer olfaction and younger age correlated with increased QOD-NS scores, whereas
      longer disease duration and older age correlated with increased QOD-PS scores.
      Females had poorer coping than males. QOD-PS scores were inversely related to QOD
      NS scores. CONCLUSIONS: The impact of olfactory loss is more significantly felt
      by younger patients with poorer olfaction. Older patients or those with longer
      disease duration develop better emotional coping abilities so as to reduce the
      impact on quality of life. It may be helpful for the patients with olfactory loss
      to develop emotional coping as early as possible to decrease the olfactory
      impact.

PMID- 21858267
TI  - The effect of a herbal combination of primrose, gentian root, vervain, elder
      flowers, and sorrel on olfactory function in patients with a sinonasal olfactory
      dysfunction.
AB  - Olfactory dysfunction is a common symptom in patients with inflammation of the
      nasal mucosa. Among numerous drugs, so far only the use of steroids has been
      shown to have a positive effect on olfactory function. Therefore the aim of the
      present study was to investigate whether patients with sinonasal disease would
      benefit in terms of olfactory function from oral treatment with a herbal drug
      (combination of primrose, gentian root, vervain, elder flowers, and sorrel:
      Sinupret(r)) which is commonly used in sinusitis. Olfactory function was tested
      using a standardised olfactory test kit ('sniffin' sticks'). The drug was applied
      in a double-blind fashion: after an initial therapy of 7 days of oral
      prednisolone for all participants with a sinonasal olfactory disease,
      participants were divided into a placebo- and a verum-group; tests were performed
      before and after treatment over a 2 months period. Statistical analysis did not
      reveal any major differences in olfactory function in relation to treatment.
      Considering that its benefit for the inflammatory component of sinusitis has been
      shown, the herbal drug may exhibit positive effects on olfactory function in a
      different setting, e.g., when applied without preceding administration of
      prednisolone, or when used in patients with certain degrees of rhinosinusitis.

PMID- 21858268
TI  - Nasal polyposis and cystic fibrosis(CF): review of the literature.
AB  - The aim of this study was to address whether NP might be a predictive factor for
      severity of CF. The authors collected data from the literature on NP as a unique
      or associated sign in CF and reviewed the clinical and molecular aspects of CF
      associated with NP. CF genotypes and clinical severity in NP(+) vs. NP(-)
      patients were reviewed, taking into account pulmonary function, frequency of P.
      aeruginosa lung infection, frequency of allergy, nutritional status, and exocrine
      pancreatic function. The CFTR gene was also analyzed in a patient with isolated
      severe NP as the unique feature of CF. This review of the literature showed a
      'milder' phenotype in 'NP+' vs. 'NP-' CF patients, contrasting with a marked
      association between NP and 'severe' CF mutations. In addition, a complex genotype
      was identified, associating four heterozygous variants, namely p.Q493X (a severe
      mutation) on the paternal allele, and p.V562I, p.A1006E, and (TG)11(T)5 (IVS8-5T)
      on the maternal allele, in a case of CF presenting as isolated NP. The authors
      speculate that genetic/environmental factors associated with NP might attenuate
      the functional impact of 'severe' CF mutations. The overrepresentation of CF
      carriers among patients with isolated NP also advocates the need for CFTR
      molecular screening in such populations for genetic counselling purposes.

PMID- 21858269
TI  - Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis
      with nasal polyps and antrochoanal polyps.
AB  - Chronic rhinosinusitis without and with nasal polyps (CRSwNP and CRSsNP), and
      antrochoanal polyps are different phenotypes with different pathomechanisms.
      Indoleamine 2,3-dioxygenase (IDO) is an enzyme expressed in many cells involved
      in the catabolism of the essential amino acid tryptophan to kynurenine. IDO might
      have a role in allergic airway inflammation. The aim was to evaluate if IDO
      expression is associated with CRSsNP, CRSwNP, or ACP. One hundred fifty specimens
      from the nasal cavity and sinus mucosa were immunohistochemically stained with
      mAb anti-IDO. The expression of epithelial and leukocyte IDO was associated with
      CRSwNP and ACP. The presence of ASA intolerance, asthma, atopy, smoking and use
      of medication did not significantly change the results. The different expression
      of IDO could putatively indicate the differences in the pathomechanisms of
      CRSsNP, CRSwNP and ACP. Further studies on the role of IDO in upper airways
      pathologies are required.

PMID- 21858270
TI  - Optical and electromagnetic tracking for navigated surgery of the sinuses and
      frontal skull base.
AB  - BACKGROUND: New hardware and software algorithms in electromagnetic tracking for
      computer assisted surgery (CAS) have been developed. We aimed to compare
      electromagnetic tracking for navigated procedures in frontal skull base surgery
      to optical tracking. METHODS: Target registration error (TRE) was determined in 6
      anatomic specimens in an experimental wet-lab. As targets, 6 titanium screws were
      evenly distributed over the surgical areas of interest from the frontal sinus to
      the clivus. Optical tracking and electromagnetic tracking was evaluated in
      identical software environment using a last generation commercially available
      navigation system. RESULTS: Submillimetric application accuracy could be achieved
      with both tracking modalities. Optical was more accurate than electromagnetic
      tracking and its reliability was better. Target position did not influence TRE,
      however TRE varied significantly from skull to skull. CONCLUSIONS: Although less
      accurate than optical tracking, electromagnetic tracking still offers excellent
      accuracy and reliability for anterior skull base surgery. Electromagnetic
      tracking is not dependent on direct line of sight between its hardware components
      and therefore easily integrated even in cluttered operating theatres.

PMID- 21858271
TI  - Endoscopic treatment of maxillary inverted papilloma.
AB  - OBJECTIVES: Evaluate the efficacy of endoscopic treatment in maxillary inverted
      papilloma (IP). METHODOLOGY: Between July 2002 - April 2008, 20 patients affected
      by maxillary localization of IP were treated in our Clinic. All patients
      underwent endoscopic treatment consisting of an endoscopic medial maxillectomy
      (simple or extended), or attachment-site endoscopic tumour surgery. RESULTS: The
      cohort was composed of 20 patients (male: 15, female: 5), mean age 58 years, and
      included 21 endoscopic resections of maxillary IP. Minimum follow-up: 24 months,
      mean follow-up: 50 months. We registered only 1 case of tumour
      persistence/recurrence after 15 months, which underwent a second endoscopic
      treatment. No association with malignant lesions was noted. The efficacy of the
      endoscopic treatment was 95% (19/20 cases) after primary surgery, and 100% after
      endoscopic revision. CONCLUSIONS: Our experience demonstrates the efficacy of
      endoscopic treatment in maxillary IP. Based On its reduced morbidity in
      comparison to external approaches and its good control of the disease, we
      consider it our standard treatment for maxillary-originated inverted papilloma.

PMID- 21858272
TI  - Revison endonasal dacryocystorhinostomies: analysis of 44 procedures.
AB  - PURPOSE: To determine the success rate of revision endoscopic
      dacryocystorhinostomies (DCR) and to analyse 44 revision DCRs. METHODS: The
      operative and postoperative data were collected in 44 revision DCRs. The
      corrections of associated structural anatomic alterations were performed during
      the surgery (resection of the scarr, the bone window creating, resection of the
      head of the middle turbinate, septoplasty, ethmoidectomy etc.) and the intubation
      was performed in all cases. RESULTS: The follow-up interval ranged from 12 to 36
      months. The 44 ReEDCRs were performed in adults and there were only 5 children
      under the age of 15. The surgery was performed under local or general
      anaesthesia. The most frequent secondary procedures were scar resections,
      creating a wider bone window, and partial middle turbinate resection. Four
      patients were excluded for their follow-up periods had not been completed. An
      average time of the tubes removal was 5.6 months. The total success rate was
      84.0%; the success rate was 85.7% in the group with closed rhinostomy and 1/2 in
      the group of canalicular and rhinostomy obstructions. CONCLUSIONS: The endonasal
      revision DCR is a safe and very effective surgical procedure following the failed
      DCRs. The correction of associated structural anatomic alterations that may be
      involved in the failure of previous surgeries can be easily performed.

PMID- 21858273
TI  - Click maltose as an alternative to reverse phase material for desalting
      glycopeptides.
AB  - Desalting peptides before mass spectrometry analysis is important because salts
      lead to adduct formation, increased chemical noise and ion suppression effect. A
      high concentration of salt can clog nanoelectrospray ionization (ESI) emitters.
      The reverse phase C18 material is commonly used to desalt peptides because of its
      high binding capacity. However, peptides with high hydrophilicity, such as
      glycopeptides, are not retained well on this material, resulting in the loss of
      peptide information. To improve the efficiency of glycopeptide desalting, we
      introduced a hydrophilic interaction chromatography (HILIC)-based material named
      click maltose. Four glycoproteins, horseradish peroxidase (HRP), human serum
      immunoglobulin G (IgG), bovine ribonuclease B (RNase B), and alpha-1 acid
      glycoprotein (AGP) were chosen as models and their glycopeptides were desalted
      with click maltose, AQ C18, Empore C18 and ZipTip C18. Click maltose as a HILIC
      material exhibited better performance than the other three C18 materials for both
      number of targeted glycopeptides and their corresponding intensities. In
      addition, accurate glycopeptide profiling was achieved with click maltose
      desalting regardless of peptide lengths and glycan types.

PMID- 21858274
TI  - A new way to detect the interaction of DNA and anticancer drugs based on the
      decreased resonance light scattering signal and its potential application.
AB  - A novel assay has been developed to detect the interaction of DNA and anticancer
      drugs based on the decreased resonance light scattering (RLS) technique. The
      proposed method can be used to study those drugs which do not produce a RLS
      signal after binding to DNA. RLS was used to monitor the interaction of five
      anticancer drugs with DNA. The reaction between anticancer drugs and DNA took
      place in BR buffer solution. From the RLS assay, the sequence of five anticancer
      drugs activities was as follows: CTX < MTX < Pt < MMC < 5-Fu. Mammary cancer cell
      DNA (mcDNA) was involved to validate the RLS assay. The results showed that the
      sensitivities of the five anticancer drugs targeting both mcDNA and ctDNA
      increased in the same order. However the sensitivity of each drug to mcDNA was
      higher than that to ctDNA It is a significant innovation of the RLS method to
      detect the interaction of DNA and anticancer drugs and to obtain drug
      sensitivity, which provides new strategies to screen DNA targeted anticancer
      drugs.

PMID- 21858275
TI  - Homogeneous Bose gas of dipolar molecules in the mean field approximation.
AB  - We present a mean field analysis of the effects of molecular rotation on the
      excitation spectrum and stability of ultracold dipolar gases. For an unpolarized
      homogeneous gas interacting with a pure dipole-dipole interaction, we find that
      for the rotational state L = 1 the dipole-dipole interaction causes a splitting
      of the translation-rotation energy levels into a single M = 0 and a doubly
      degenerate M = +/-1 excitation. For all other rotational states, the dipole
      dipole interaction does not lead to coupling of translations and rotations and
      therefore has no effect on the rotational degeneracy of the excitations. The
      addition of arbitrarily small electric fields is found to introduce instabilities
      similar to those known to arise in the fully polarized dipolar gas. As in the
      case of a fully polarized gas, addition of a large enough short range repulsive
      potential is seen to stabilize the system, with the critical value of the
      repulsive interaction required for stabilization being larger when rotations are
      included.

PMID- 21858276
TI  - The vapour of imidazolium-based ionic liquids: a mass spectrometry study.
AB  - Eight common dialkylimidazolium-based ionic liquids have been successfully
      evaporated in ultra-high vacuum and their vapours analysed by line of sight mass
      spectrometry using electron ionisation. The ionic liquids investigated were 1
      alkyl-3-methylimidazolium bis[(trifluoromethane)sulfonyl]imide,
      [C(n)C(1)Im][Tf(2)N] (where n = 2, 4, 6, 8), 1-alkyl-3-methylimidazolium
      tetrafluoroborate, [C(n)C(1)Im][BF(4)] (where n = 4, 8), 1-butyl-3
      methylimidazolium octylsulfate, [C(4)C(1)Im][C(8)OSO(3)] and 1-butyl-3
      methylimidazolium tetrachloroferrate, [C(4)C(1)Im][FeCl(4)]. All ionic liquids
      studied here evaporated as neutral ion pairs; no evidence of decomposition
      products in the vapour phase were observed. Key fragment cations of the ionised
      vapour of the ionic liquids are identified. The appearance energies, E(app), of
      the parent cation were measured and used to estimate the ionisation energies,
      E(i), for the vapour phase neutral ion pairs. Measured ionisation energies ranged
      from 10.5 eV to 13.0 eV. Using both the identity and E(app) values, the
      fragmentation pathways for a number of fragment cations are postulated. It will
      be shown that the enthalpy of vaporisation, Delta(vap)H, can successfully be
      measured using more than one fragment cation, although caution is required as
      many fragment cations can also be formed by ionisation of decomposition products.

PMID- 21858278
TI  - Laser inactivation protein patterning of cell culture microenvironments.
AB  - Protein micropatterned substrates have emerged as important tools for studying
      how cells interact with their environment, as well as allowing useful
      experimental control over, for example, cell shape and cell position on a
      surface. Here we present a new approach for protein micropatterning in which a
      focused laser is used to locally inactivate proteins on a protein-coated
      substrate. By translating the laser relative to the substrate, protein patterns
      of essentially arbitrary shape can be produced. This approach has a number of
      useful features. To begin, it is a maskless writing approach. Thus new patterns
      can be designed and implemented quickly. Laser inactivation can also be performed
      on a number of different substrate materials, ranging from glass to
      polydimethylsiloxane. Further, the inactivation is dose dependent, thus complex
      gradients and other non-uniform distributions of proteins can be produced.
      Because the focus of the laser can be changed quickly, laser-based patterning can
      also be applied to substrates with complex topographies or enclosed surfaces--as
      long as an optical path is available. To demonstrate this capability, protein
      patterns were made on the inside of small quartz capillary tubes. Patterned
      substrates produced using laser inactivation constrain cell shape in predictable
      ways, and we show that these substrates are compatible with a number of different
      eukaryotic cell lines.

PMID- 21858279
TI  - A pi-stacked phenylacetylene dimer.
AB  - The structure of the phenylacetylene-dimer has been elucidated using IR-UV double
      resonance spectroscopy in combination with high level ab initio calculations at
      the CCSD(T)/CBS level. The IR spectra in the acetylenic and the aromatic C-H
      stretching regions indicate that the two phenylacetylene moieties are in
      identical environments and very similar to the phenylacetylene monomer.
      Calculated stabilization energies and the free energies at the CCSD(T)/CBS level
      favor the formation of an anti-parallel pi-stacked structure. The DFT-SAPT energy
      decomposition analysis points out that the anti-parallel pi-stacked structure
      maximizes electrostatic as well as the dispersion components of energy. The
      observed IR spectra are consistent with the anti-parallel pi-stacked structure.

PMID- 21858280
TI  - A novel synthesis method to produce silver-doped CeO2 nanotubes based on Ag
      nanowire templates.
AB  - Silver nanowires were used as templates to synthesize silver-doped CeO(2) (Ag
      CeO(2)) nanotubes by the precipitation method. The precipitated solid was dried
      at 100  degrees C for 24 h and calcined at 500  degrees C for 5 h. A TEM, HRTEM,
      LV-SEM and XRD study was carried out to determine the micro and nanostructural
      characteristics of the samples. LV-SEM analysis allowed us to observe
      microtubular empty structures constituted by Ce, O and Ag as indicated by EDS.
      These tubular structures, with an external diameter from 120 to 280 nm and an
      internal diameter from 40 to 80 nm, were mainly composed of 11 nm ceria
      nanoparticles. This kind of structures was obtained when CeO(2) nanoparticles
      covered the Ag nanowires during the synthesis. Due to the presence of ammonium
      hydroxide used during the synthesis, a fraction of the silver nanowire reacts and
      Ag atoms begin to migrate outside the ceria microtube. When the sintering process
      is applied, the Kirkendall effect can occur. So, out-diffusion of the remnant Ag
      through the interface is faster than the in-diffusion of the shell material
      (CeO(2)), which eventually results in a coaxial nanotube on completion of the non
      equilibrium interdiffusion, leaving the central core completely empty, driving
      the formation of hollow tubular Ag-CeO(2) structures as a result.

PMID- 21858281
TI  - Radical cation (C(+)-pi) and radical anion (A(-)-pi) interactions with aromatic
      rings: energetic, orbitalic and spin density considerations.
AB  - Cation and anion-pi interactions are important binding forces where aromatic
      rings are involved. In this manuscript we define and compare two related
      interactions that have not been reported so far, namely radical cation and
      radical anion-pi interactions (C(+)-pi and A(-)-pi, respectively). Moreover, we
      compare the energetic features of these complexes with the related closed-shell
      interactions. Interestingly the C(+)-pi interaction is more favourable than the
      standard cation-pi interaction and the contrary is observed for the A(-)-pi
      interaction. Changes in the aromatic character of the ring upon complexation of
      the ion have been studied using the nucleus-independent chemical shift (NICS)
      criterion. Orbitalic and spin density calculations of the complexes have been
      computed in order to investigate if spin transfer effects between the radical
      ions and the aromatic ring exist. We have analyzed the physical nature of the
      interactions by means of Bader's theory of "atoms-in-molecules" and partitioning
      the total interaction energy into individual components using the Molecular
      Interaction Potential with a polarization partition scheme. Finally, we describe
      an interesting biological example, which involves the tetrahydrobiopterin
      cofactor, where the presence of a radical ion-pi interaction is important.

PMID- 21858282
TI  - Poisson-Boltzmann continuum-solvation models: applications to pH-dependent
      properties of biomolecules.
AB  - All molecules can be viewed as either discrete or continuous assemblies of
      electric charges, and electrostatics plays a major role in intermolecular and
      intramolecular interactions. Moreover, charge distribution within molecules may
      fluctuate due to the presence of ionizable groups capable of exchanging protons
      with the environment, leading to pH-dependence of phenomena involving such
      molecules. Electrostatic aspects of complex shapes and environments of biological
      molecules, in vitro and in vivo, are relatively well amenable to treatment by
      Poisson-Boltzmann models, which are attractive in that they possess a clear
      physical meaning, and can be readily solved by several mathematically sound
      methods. Here we describe applications of these models to obtain valuable
      insights into some biologically important pH-dependent properties of
      biomolecules, such as stability, binding of ligands (including potential drugs),
      enzymatic activity, conformational transitions, membrane transport and viral
      entry.

PMID- 21858283
TI  - Decreasing the sialidase activity of multifunctional Pasteurella multocida alpha2
      3-sialyltransferase 1 (PmST1) by site-directed mutagenesis.
AB  - Pasteurella multocida alpha2-3-sialyltransferase 1 (PmST1) is a multifunctional
      enzyme which has alpha2-6-sialyltransferase, alpha2-3-sialidase, and alpha2-3
      trans-sialidase activities in addition to its major alpha2-3-sialyltransferase
      activity. The presence of the alpha2-3-sialidase activity of PmST1 complicates
      its application in enzymatic synthesis of alpha2-3-linked sialosides as the
      product formed can be hydrolyzed by the enzyme. Herein we show that the alpha2-3
      sialidase activity of PmST1 can be significantly decreased by protein crystal
      structure-based site-directed mutagenesis. A PmST1 double mutant E271F/R313Y
      showed a significantly (6333-fold) decreased sialidase activity without affecting
      its alpha2-3-sialyltransferase activity. The double mutant E271F/R313Y,
      therefore, is a superior enzyme for enzymatic synthesis of alpha2-3-linked
      sialosides.

PMID- 21858289
TI  - Yb(OTf)3 catalyzed new cascade reaction: a facile assembly of fused
      quinazolinones.
AB  - A one-pot Yb(III)-mediated cascade reaction has been developed leading to small
      molecules based on a novel structural motif, i.e. quinazolin-4-one moiety fused
      with an isoquinoline ring, for potential inhibition of TNF-alpha.

PMID- 21858290
TI  - Crystal-like microporous hybrid solid nanocast from Cr-MIL-101.
AB  - A crystal-like ordered microporous inorganic hybrid solid was prepared using
      silane functionalized Cr-MIL-101 (Si-MIL-101) as the precursor, via a surface
      coating reinforced framework strategy.

PMID- 21858291
TI  - Fluorescent and pH-responsive diblock copolymer-coated core-shell CdSe/ZnS
      particles for a color-displaying, ratiometric pH sensor.
AB  - A color distinctive, ratiometric pH sensor was demonstrated using pH responsive
      and fluorescent (PyMMP-b-P2VP) diblock copolymer coated CdSe/ZnS QDs. Due to the
      change in the P2VP conformations in response to pH change, the color of QDs in
      solution changes distinctly from blue to red.

PMID- 21858292
TI  - Absorption and emission spectra of fluorescent silica nanoparticles from TD
      DFT/MM/PCM calculations.
AB  - A multi-scale computational protocol, which combines Quantum Mechanics and
      Molecular Mechanics (QM/MM) calculations with the polarisable continuum model
      (PCM), has been used to study the tetramethylrhodamine isothiocyanate (TRITC)
      fluorophore, embedded in three different environments, namely in water, on an
      amorphous silica surface and covalently encapsulated in a silica nanoparticle (C
      dot). Absorption and emission spectra have been simulated by using TD-B3LYP/PCM
      calculations, performed on the TRITC ground and excited state geometries,
      optimized at the QM/MM level. The results are in good agreement with experimental
      data confirming the caging effect played by the silica shell on the mobility of
      the TRITC molecule when covalently encapsulated in silica nanoparticles. This
      could result in a decrease of the nonradiative decay rate and thus an increase of
      the quantum yield of the molecule.

PMID- 21858293
TI  - Engineering DNA-based functional materials.
AB  - While DNA is a genetic material, it is also an inherently polymeric material made
      from repeating units called nucleotides. Although DNA's biological functions have
      been studied for decades, the polymeric features of DNA have not been extensively
      exploited until recently. In this tutorial review, we focus on two aspects of
      using DNA as a polymeric material: (1) the engineering methods, and (2) the
      potential real-world applications. More specifically, various strategies for
      constructing DNA-based building blocks and materials are introduced based on DNA
      topologies, which include linear, branched/dendritic, and networked. Different
      applications in nanotechnology, medicine, and biotechnology are further reviewed.

PMID- 21858294
TI  - Design, synthesis, characterization, luminescence and non-linear optical (NLO)
      properties of multinuclear platinum(II) alkynyl complexes.
AB  - A series of luminescent multinuclear platinum(II) alkynyl complexes containing
      triethynylbenzene or 1,4-bis(3,5-diethynylphenyl)buta-1,3-diyne as cores has been
      successfully synthesized and characterized. The electronic absorption, emission,
      nanosecond transient absorption and electrochemical properties of these complexes
      have been reported. These complexes show long-lived emissions in degassed benzene
      solution and in alcoholic glass at 77 K. Moreover, they are found to exhibit two
      photon absorption (2PA) and two-photon induced luminescence (TPIL) properties,
      and their two-photon absorption cross-sections have been determined to be 6-191
      GM upon excitation at 720 nm. Through a systematic comparison, it has been found
      that tetra- and hexanuclear platinum(II) complexes show better 2PA and TPIL
      properties than their di- and trinuclear counterparts.

PMID- 21858295
TI  - Modeling the cellular impact of nanoshell-based biosensors using mouse alveolar
      macrophage cultures.
AB  - In this study, the relative toxicity of native gold-silica nanoshells (NS) has
      been compared to nanoshells modified with poly(ethylene glycol)-thiol (PEG-SH)
      and a Raman-active PEG, p-mercaptoaniline-poly(ethylene glycol) (pMA-PEG), in
      mouse alveolar macrophage cell cultures (RAW 264.7). The results from toxicity
      profiling using an MTT assay demonstrate that cell viability post-particle
      exposure is a function of three factors: nanoshell concentration, surface
      functionalization, and incubation time. By minimizing particle concentrations and
      incubation times, cell cultures are able to recover within 24 h of nanoshell
      removal, indicative of nanoshells having more of a cytostatic versus cytotoxic
      effect on macrophage cells. The mechanism of the cytostatic effect has been
      investigated by imaging the presence of reactive oxygen species (ROS) using a
      fluorescence assay kit (Image-iTTM LIVE) after the introduction of NS to the cell
      cultures. Elevated ROS signals are seen in the cells containing higher
      concentration of NS, and indicate that the major reason of toxicity may due to
      the oxidative stress caused by excess NS particles. Raman imaging experiments
      with pMA-PEG coated nanoshells showed that cells exposed for even short exposure
      times (~2 h) retained those particles up to 24 h after exposure, while migration
      experiments suggest that surviving cells retain their nanoshells and may
      reallocate them to progeny cells upon cell division.

PMID- 21858296
TI  - Determination of ranitidine, nizatidine, and cimetidine by a sensitive
      fluorescent probe.
AB  - A validated, simple, and sensitive fluorescence quenching method for the
      determination of ranitidine, nizatidine, and cimetidine in tablets and biological
      fluids is presented. This is the first single fluorescence method reported for
      the analysis of all three H(2) antagonists. The competitive reaction between the
      investigated drug and the palmatine probe for the occupancy of the
      cucurbit[7]uril (CB[7]) cavity was studied using spectrofluorometry. CB[7] was
      found to react with the probe to form a stable complex. The fluorescence
      intensity of the complex was also enhanced greatly. However, the addition of the
      drug dramatically quenched the fluorescence intensity of the complex.
      Accordingly, a new fluorescence quenching method for the determination of the
      studied drugs was established. The different experimental parameters affecting
      the fluorescence quenching intensity were studied carefully. At optimum reaction
      conditions, the rectilinear calibration graphs between the fluorescence quenching
      values (DeltaF) and the medicament concentration were obtained in the
      concentration range of 0.04-1.9 MUg mL(-1) for the investigated drugs. The limits
      of detection ranged from 0.013 to 0.030 MUg mL(-1) at 495 nm using an excitation
      wavelength of 343 nm. The proposed method can be used for the determination of
      the three H(2) antagonists in raw materials, dosage forms and biological fluids.

PMID- 21858297
TI  - Microbiosensors based on DNA modified single-walled carbon nanotube and Pt black
      nanocomposites.
AB  - Glucose and ATP biosensors have important applications in diagnostics and
      research. Biosensors based on conventional materials suffer from low sensitivity
      and low spatial resolution. Our previous work has shown that combining single
      walled carbon nanotubes (SWCNTs) with Pt nanoparticles can significantly enhance
      the performance of electrochemical biosensors. The immobilization of SWCNTs on
      biosensors remains challenging due to the aqueous insolubility originating from
      van der Waals forces. In this study, we used single-stranded DNA (ssDNA) to
      modify SWCNTs to increase solubility in water. This allowed us to explore new
      schemes of combining ssDNA-SWCNT and Pt black in aqueous media systems. The
      result is a nanocomposite with enhanced biosensor performance. The surface
      morphology, electroactive surface area, and electrocatalytic performance of
      different fabrication protocols were studied and compared. The ssDNA-SWCNT/Pt
      black nanocomposite constructed by a layered scheme proved most effective in
      terms of biosensor activity. The key feature of this protocol is the exploitation
      of ssDNA-SWCNTs as molecular templates for Pt black electrodeposition. The
      glucose and ATP microbiosensors fabricated on this platform exhibited high
      sensitivity (817.3 nA/mM and 45.6 nA/mM, respectively), wide linear range (up to
      7 mM and 510 MUM), low limit of detection (1 MUM and 2 MUM) and desirable
      selectivity. This work is significant to biosensor development because this is
      the first demonstration of ssDNA-SWCNT/Pt black nanocomposite as a platform for
      constructing both single-enzyme and multi-enzyme biosensors for physiological
      applications.

PMID- 21858298
TI  - A colorimetric and ratiometric fluorescent probe for quantification of bovine
      serum albumin.
AB  - A 4-aminonaphthalimide-based ratiometric fluorescent probe 1 employing the
      internal charge transfer (ICT) mechanism was designed and synthesized to detect
      bovine serum albumin (BSA). The interaction of 1 and BSA was investigated by
      fluorescence and UV-vis absorption spectroscopy. Upon treatment with BSA, the
      probe successfully exhibited a ratiometric fluorescent response at 540 nm and 480
      nm. The fluorescent intensity ratio at 540 nm and 480 nm (F(540)/F(480))
      increases linearly with BSA concentration in the range of 0-75.0 MUg mL(-1) and
      the detection limit was about 2.4 ng mL(-1). Our strategy is expected to provide
      a methodology to quantify BSA either by a normal or by a ratiometric and
      colorimetric way with high sensitivity.

PMID- 21858299
TI  - The effect of dipole moment and electron deficiency of analytes on the
      chemiresistive response of TiO2(B) nanowires.
AB  - Nanostructured TiO(2)(B) thin films were found to have strong and fast
      chemiresistive response to nitro-aromatic and nitro-amino explosives recently. In
      this study, the effects of dipole moment and electron deficiency of the analyte
      molecules on the chemiresistive response are explored to understand the details
      of molecular interactions of analytes with the sensor surface which lead to
      charge depletion and the chemiresistive effect. It was found that the speed of
      the response is dominated by the polarity of the analytes and molecules with
      larger dipole moments produce faster responses. The degree of the response was
      found to be dominated by the electron deficiency of the analytes and molecules
      with greater electron deficiency produce stronger chemiresistive responses.

PMID- 21858300
TI  - Analysis of degradation products of chemical warfare agents using capillary
      electrophoresis.
AB  - Analysis of chemical warfare agents (CWAs), their precursors and degradation
      products (DPs) is an important verification component in support of the Chemical
      Weapons Convention and urgently demanding rapid and reliable analytical methods.
      Considering a growing number of papers presented in the last years in the field
      of capillary electrophoresis (CE) of DPs, this review article gives an overview
      on CE techniques which are feasible for the determination of DPs with the
      advantages of using relatively simple and inexpensive research instrumentation,
      reduced consumption of potentially toxic samples, shorter sample preparation
      times, etc. A brief introduction is provided into the chemical background of CWAs
      followed by a documented appraisal that the CE method is well suited to deal with
      polar, acidic DPs mostly occurring in aqueous samples or extracts. Applications
      of CE to the separation of DPs are described, complemented by a critical
      discussion of the detection techniques, including mostly conductivity, laser
      induced fluorescence, UV absorption and mass spectrometry. This review also
      includes actual development regarding the challenges of CE in analyses of
      different DPs from real samples, often avoided by in- and off-line pre
      concentration techniques or the coupling of CE to selective detection methods.
      Special emphasis is placed on the miniaturised CE systems that have the potential
      of being before long developed into a field deployable and potentially disposable
      platform for routine DP monitoring in environmental samples.

PMID- 21858301
TI  - Dynamic light scattering as an efficient tool to study glyconanoparticle-lectin
      interactions.
AB  - Glyconanomaterials, an emerging class of bio-functional nanomaterials, have shown
      promise in detecting, imaging and targeting proteins, bacteria, and cells. In
      this article, we report that dynamic light scattering (DLS) can be used as an
      efficient tool to study glyconanoparticle (GNP)--lectin interactions. Silica and
      Au nanoparticles (NPs) conjugated with D-mannose (Man) and D-galactose (Gal) were
      treated with the lectins Concanavalin A (Con A) and Ricinus communis agglutinin
      (RCA(120)), and the hydrodynamic volumes of the resulting aggregates were
      measured by DLS. The results showed that the particle size grew with increasing
      lectin concentration. The limit of detection (LOD) was determined to be 2.9 nM
      for Con A with Man-conjugated and 6.6 nM for RCA(120) with Gal-conjugated silica
      NPs (35 nm), respectively. The binding affinity was also determined by DLS and
      the results showed 3-4 orders of magnitude higher affinity of GNPs than the free
      ligands with lectins. The assay sensitivity and affinity were particle size
      dependent and decreased with increasing particle diameter. Because the method
      relies on the particle size growth, it is therefore general and can be applied to
      nanomaterials of different compositions.

PMID- 21858302
TI  - Self-assembly of a peptide amphiphile based on hydrolysed Bombyx mori silk
      fibroin.
AB  - An octapeptide, GAGAGAGY, was obtained by a novel method, i.e. hydrolysing Bombyx
      mori silk fibroin. Afterward, a dodecanoic acid-peptide conjugation was
      synthesized. This amphiphile assembled into cylindrical nanofibers of planar beta
      sheets at pH 9 and twisted beta-sheets at pH 4.

PMID- 21858303
TI  - A facile one-pot sonochemical synthesis of surface-coated mannosyl protein
      microspheres for detection and killing of bacteria.
AB  - We report a remarkably facile one-pot sonochemical approach to prepare protein
      microspheres whose shells are covalently decorated with a mannosyl derivative to
      target Escherichia coli (E. coli), while their cores are encapsulated with
      tetracycline. Conjugated microspheres induced the agglutination of E. coli and
      increased the anti-bacterial activity of the encapsulated tetracycline by five
      fold.

PMID- 21858304
TI  - Superquencher formation via nucleic acid induced noncovalent perylene probe self
      assembly.
AB  - A fluorophore labeled oligonucleotide could induce aggregation of a positively
      charged perylene probe. The perylene aggregate could very efficiently quench the
      fluorescence of the labeled fluorophore. Based on this observation, a new method
      for the highly sensitive and selective detection of a protein has been developed.

PMID- 21858305
TI  - A melanin-inspired pro-oxidant system for dopa(mine) polymerization: mimicking
      the natural casing process.
AB  - An oxygen-dependent biomimetic system for DOPA, dopamine and norepinephrine
      polymerization exploiting the redox properties of a 5-S-cysteinylDOPA (CD)
      melanin polymer is disclosed. Kinetic, chemical and scanning electron microscopy
      (SEM) evidence indicates conversion of DOPA into a black insoluble polymer
      encapsulating the active CD-melanin core.

PMID- 21858306
TI  - One-step-impregnation hard templating synthesis of high-surface-area
      nanostructured mixed metal oxides (NiFe2O4, CuFe2O4 and Cu/CeO2).
AB  - We report here on an efficient one-step-impregnation method to synthesize
      crystalline mesoporous bimetal oxides (e.g. NiFe(2)O(4), CuFe(2)O(4), Cu/CeO(2))
      using mesoporous silicas as hard templates under optimized mixing conditions.
      This new procedure enables a true replication of the mesostructure with high
      yield and phase purity, while retaining particle morphology of the template.

PMID- 21858307
TI  - Kinetically grafting G-quadruplexes onto DNA nanostructures for structure and
      function encoding via a DNA machine.
AB  - Kinetically grafting G-quadruplexes onto one-dimensional DNA nanostructures with
      precise positioning was realized in this study. The programs hold great promise
      for label-free and enzyme-free detection of various targets as a result of signal
      amplification from G-quadruplexes, and building DNA nanostructures as scaffolds
      due to the molecular recognition capacity of G-quadruplex aptamers.

PMID- 21858309
TI  - Sharp separation of C2/C3 hydrocarbon mixtures by zeolitic imidazolate framework
      8 (ZIF-8) membranes synthesized in aqueous solutions.
AB  - Exceptional high quality ZIF-8 membranes prepared through a novel seeded growth
      method in aqueous solutions at near room temperature exhibit excellent separation
      performance for C2/C3 hydrocarbon mixtures. The separation factors for mixtures
      of ethane/propane, ethylene/propylene and ethylene/propane are ~80, ~10 and ~167,
      respectively.

PMID- 21858308
TI  - Electron transfer reduction of unactivated esters using SmI2-H2O.
AB  - The reduction of unactivated esters using samarium diiodide is reported for the
      first time. The optimised protocol allows for the reduction of primary, secondary
      and tertiary alkyl esters in excellent yields and is competitive with reductions
      mediated by metal hydrides and alkali metals.

PMID- 21858311
TI  - Palladium-catalyzed cross-coupling reactions of aryl mesylates.
AB  - Palladium-catalyzed cross-coupling reactions are state-of-the art methods for
      synthesis of many important compounds. The development of the use of the phenol
      derived sulfonated hydroxyl group in the coupling reactions is highly attractive
      as the hydroxyl group is commonly present in organic compounds and they are
      versatile alternatives to aryl halides in cross-coupling reactions. In this
      tutorial review, we summarize the current development of palladium-catalyzed
      cross-coupling reactions of aryl mesylates.

PMID- 21858310
TI  - Probing molecular kinetics with Markov models: metastable states, transition
      pathways and spectroscopic observables.
AB  - Markov (state) models (MSMs) have attracted a lot of interest recently as they
      (1) can probe long-term molecular kinetics based on short-time simulations, (2)
      offer a way to analyze great amounts of simulation data with relatively little
      subjectivity of the analyst, (3) provide insight into microscopic quantities such
      as the ensemble of transition pathways, and (4) allow simulation data to be
      reconciled with measurement data in a rigorous and explicit way. Here we sketch
      our current perspective of Markov models and explain in short their theoretical
      basis and assumptions. We describe transition path theory which allows the entire
      ensemble of protein folding pathways to be investigated and that combines
      naturally with Markov models. Experimental observations can be naturally linked
      to Markov models with the dynamical fingerprint theory, by which experimentally
      observable timescales can be equipped with an understanding of the structural
      rearrangement processes that take place at these timescales. The concepts of this
      paper are illustrated by a simple kinetic model of protein folding.

PMID- 21858312
TI  - Design and synthesis of luminescence chemosensors based on alkynyl phosphine
      gold(I)-copper(I) aggregates.
AB  - Receptor-containing polynuclear mixed-metal complexes of gold(I)-copper(I) 1-3
      based on a [{Au(3)Cu(2)(C=CPh)(6)}Au(3){PPh(2)-C(6)H(4)-PPh(2)}(3)](2+)
      (Au(6)Cu(2)) core with benzo-15-crown-5, oligoether and urea binding sites were
      designed and synthesized, respectively. These complexes exhibited remarkably
      strong red emission at ca. 619-630 nm in dichloromethane solution at room
      temperature upon photoexcitation at lambda > 400 nm, with the emission quantum
      yield in the range 0.59-0.85. The cation-binding properties of 1 and 2 and the
      anion-binding properties of 3 were studied using UV-vis, emission and (1)H NMR
      techniques. Complex 1, with six benzo-15-crown-5 pendants, was found to show a
      higher binding preference for K(+), with a selectivity trend of K(+)? Cs(+) >
      Na(+) > Li(+). The addition of metal ions (Li(+), Na(+), K(+) and Cs(+)) to
      complex 1 led to a modest emission enhancement with a concomitant slight blue
      shift in energy and well-defined isoemissive points, which is attributed to the
      rigidity of the structure and the inhibited PET (photo-induced electron transfer)
      process from the oxygen to the aggregate as a result of the binding of the metal
      ion. The six urea receptor groups on complex 3 were found to form multiple
      hydrogen bonding interactions with anions, with the positive charge providing
      additional electrostatic interaction for anion-binding. The anion selectivity of
      3 follows the trend F(-) > Cl(-)~ H(2)PO(4)(-) > Br(-) and the highest affinity
      towards F(-) is attributed to the stronger basicity of F(-), as well as its good
      size match with the cavity of the urea pocket.

PMID- 21858313
TI  - A versatile water soluble fluorescent probe for ratiometric sensing of Hg2+ and
      bovine serum albumin.
AB  - A novel tetraazamacrocycle fluorescent sensor (6-(1-(dimethylamino)-5-naphthalene
      sulfonyl)-3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene, 1) has
      been designed and prepared, which can be utilized for selective and ratiometric
      sensing of Hg(2+) and bovine serum albumin (BSA) with two different responsive
      modes in aqueous solution at physiological pH (50 mM Tris-HCl, pH 7.6). Above 0.5
      ppb Hg(2+) can be discerned by coordination with 1 and the emission color changes
      enable 1 to be applied to a fast Hg(2+) test paper assay. Sensor 1 has also been
      demonstrated to be easily cell-penetrable and applicable for Hg(2+) imaging in
      living cells. Imaging of BSA in the gel using SDS-PAGE (sodium dodecyl sulfate
      polyacrylamide gel electrophoresis) stained in the medium containing 1 verified
      that the binding of 1 and BSA was successful in the presence of nonprotein
      substances. The linear range of 1 towards BSA utilizing ratiometric fluorescent
      calibration via noncovalent interaction in solution is 0-100 MUg mL(-1) with a
      detection limit of 1 MUg mL(-1), and has been successfully employed to determine
      the albumin concentration in blood serum by means of ratiometric fluorescent
      measurements for the first time. Finally, sensor 1 behaves as a fluorescent
      molecular switch composed of triple logic gates upon chemical inputs of Hg(2+)
      and BSA, which potentially provides intelligent diagnostics for Hg(2+)
      contaminated serum on the nanoscale.

PMID- 21858315
TI  - Spin crossover in polymeric and heterometallic FeII species containing polytopic
      dipyridylamino-substituted-triazine ligands.
AB  - We report the synthesis and characterisation of the new polytopic ligands, ddta
      (N,N-di(pyridin-2-yl)-4,6-di(1,4,7,10-tetraoxa-13-azacyclopentadecan-13-yl)-1,3,5
      triazin-2-amine) and tptd (N(2),N(2),N(4),N(4)-tetra(pyridin-2-yl)-6-(1,4,7,10
      tetraoxa-13-azacyclopentadecan-13-yl)-1,3,5-triazine-2,4-diamine). Each contains
      N-donor dipyridylamino binding sites as well as separate and distinct mono-aza-15
      crown-5 binding sites. The ligand ddta has been used to synthesise the polymeric
      heterometallic SCO compound trans
      [Fe(II)(NCS)(2)(ddta)(2)Na(2)](ClO(4))(2).4CH(3)CH(2)CH(2)OH, 1, and tptd has
      been used to synthesise the polymeric SCO compound trans
      [Fe(II)(NCS)(2)(tptd)].CH(3)OH, 2, and the dinuclear compound cis
      [(Fe(II))(2)(NCS)(4)(tptd)(2)], 3. Magnetic susceptibility measurements show that
      1 and a desolvated sample of 2 each undergo a gradual, one-step spin transition
      with T(1/2) values of ~240 K and ~110 K, respectively. The paucity of inter-chain
      intermolecular interactions, as well as the flexible, covalent bridges between
      Fe(II) spin crossover sites, are likely to contribute to the gradual nature of
      the spin transition observed in each case. Variable temperature powder X-ray
      diffraction studies on 1 show the anisotropic behaviour of the unit cell
      parameters, where c and the b-c plane are most affected by structural changes
      occurring as the temperature is lowered.

PMID- 21858314
TI  - Effect of substitution and planarity of the ligand on DNA/BSA interaction, free
      radical scavenging and cytotoxicity of diamagnetic Ni(II) complexes: a systematic
      investigation.
AB  - Four new bivalent nickel hydrazone complexes have been synthesised from the
      reactions of [NiCl(2)(PPh(3))(2)] with H(2)L {L = dianion of the hydrazones
      derived from the condensation of salicylaldehyde or o-hydroxy acetophenone with p
      toluic acid hydrazide (H(2)L(1)) (1), (H(2)L(2)) (2) and o-hydroxy acetophenone
      or o-hydroxy naphthaldehyde with benzhydrazide (H(2)L(3)) (3) and (H(2)L(4)) (4)}
      and formulated as [Ni(L(1))(PPh(3))] (5), [Ni(L(2))(PPh(3))] (6),
      [Ni(L(3))(PPh(3))] (7) and [Ni(L(4))(PPh(3))] (8). Structural characterization of
      complexes 5-8 were accomplished by using various physico-chemical techniques. In
      order to study the influence of substitution in the ligand and its planarity on
      the biological activity of complexes 5-8 containing them, suitable hydrazone
      ligands 1-4 have been selected in this study. Single crystal diffraction data of
      complexes 5, 7 and 8 proved the geometry of the complexes to be distorted square
      planar with a 1 : 1 ratio between the metal ion and the coordinated hydrazones.
      To provide more insight on the mode of action of complexes 5-8 under biological
      conditions, additional experiments involving their interaction with calf thymus
      DNA (CT DNA) and bovine serum albumin (BSA) were monitored by UV-visible and
      fluorescence titrations respectively. Further, the ligands 1-4 and corresponding
      nickel(ii) chelates 5-8 have been tested for their scavenging effect towards OH
      and O(2)(-) radicals. The effect of complexes 5-8 to arrest the growth of HeLa
      and Hep-2 tumour cell lines has been studied along with the cell viability
      against the non-cancerous NIH 3T3 cells under in vitro conditions.

PMID- 21858316
TI  - Mercury fate in ageing and melting snow: development and testing of a controlled
      laboratory system.
AB  - A snow cover can modify when, to what extent, and in what form atmospherically
      deposited mercury is released to the underlying surface media and/or back to the
      atmosphere. Investigations of mercury transport and transformation processes in
      snow packs are hampered by the difficulty in controlling experimental and melt
      conditions and due to the huge variability in the composition and physical
      structure of environmental snow packs. A method was developed that allows the
      detailed mechanistic investigation of mercury fate in snow that is made, aged and
      melted under controlled laboratory conditions. A number of control samples
      established that mercury in indoor air, scavenged during the snow making process,
      constitutes the dominant source of mercury in the artificial snow. No addition of
      mercury is required. The amount of mercury in fresh snow was quantitatively (102
      and 106% in two experiments) recovered in the dissolved and particulate fractions
      of the melt water and the vessel head space, confirming a mass balance for
      mercury and the absence of unquantifiable mercury sources and sinks in the
      experimental system. In snow made from unmodified tap water, more than half of
      the mercury present in the snowpack was recovered from the bottom of the snow
      vessel after all of the snow had melted. Such late elution is indicative of
      mercury being mostly associated with particles that are filtered by, and retained
      in, the shrinking snowpack. Addition of salt to the snow-making water at an
      environmentally realistic pH notably shifted the distribution of mercury in the
      snowpack from the particulate to the dissolved phase, resulting in more than 60%
      of the mercury eluting in the dissolved phase of early melt water fractions.

PMID- 21858318
TI  - New apocarotenoids and beta-carotene cleavage in Blakeslea trispora.
AB  - Mixed cultures of strains of opposite sex ("mated" cultures) of Blakeslea
      trispora contain trisporic acids and other apocarotenoids, some of which mediate
      the sexual responses of this fungus and other Mucorales. In mated cultures of the
      wild-type strains F986 and F921 we identified eleven apocarotenoids: two C(18)
      trisporoids, three C(15) compounds with a monocyclofarnesane skeleton, a C(13)
      compound, and five C(7) compounds with a 2-methylhexane skeleton. Six of them are
      new natural products and two others are new for Blakeslea. Their structures were
      established by NMR and mass spectra and those of the C(7) and C(13) compounds
      were confirmed by chemical synthesis. The finding of these compounds and the
      presence of approximately equimolecular amounts of the C(18), C(15), and C(7)
      families led to the conclusion that beta-carotene is initially split in three
      fragments by cleavage of its 13,14 and 11',12' double bonds.

PMID- 21858317
TI  - Spirocyclic systems derived from pyroglutamic acid.
AB  - The synthesis and likely conformational structure of rigid spirocyclic bislactams
      and lactam-lactones derived from pyroglutamic acid, and their suitability as lead
      structures for applications in drug development programmes using cheminformatic
      analysis, has been investgated.

PMID- 21858319
TI  - Asymmetric synthesis of alpha,beta-diamino acid derivates via Mannich-type
      reactions of a chiral Ni(II) complex of glycine with N-tosyl imines.
AB  - A practical procedure composed of an asymmetric Mannich-type reaction between N
      tosyl imine and a Ni(II) complex of glycine with (R)-o-[N-(N
      benzylprolyl)amino]bezaophenone (BPB) as a chiral auxiliary catalyzed by Et(3)N
      in DMF to (R,2R,3S)-complexes, and decomposition of products with HCl to offer
      syn-(2R,3S)-alpha,beta-diamino acids, was developed. Stereochemical mechanism of
      the Mannich reaction was proposed and supported by determining the absolute
      configuration of the product of the Mannich reaction relying on X-ray analysis.
      This two-step approach to amino acids was a general method and adapted to large
      scale preparation.

PMID- 21858320
TI  - Intramolecular Povarov reactions involving 3-aminocoumarins.
AB  - A series of pentacyclic heterocyclic systems (15 examples, 69-89%) have been
      synthesized using intramolecular Povarov reactions involving 3-aminocoumarins and
      O-cinnamylsalicylaldehydes. The Povarov adducts are formed with high selectivity
      for the trans,trans relative stereochemistry in the newly-formed [6,6] fused ring
      system. One example of a Povarov adduct featuring a new [6,5] fused ring system
      is reported. In this case, cis,trans relative stereochemistry was preferred.

PMID- 21858321
TI  - Enantioselective Morita-Baylis-Hillman reaction promoted by L-threonine-derived
      phosphine-thiourea catalysts.
AB  - A series of bifunctional phosphine-thiourea organic catalysts based on natural
      amino acid scaffolds were designed and prepared. L-threonine-derived bifunctional
      phosphine catalysts were found to be very efficient in promoting asymmetric
      Morita-Baylis-Hillman (MBH) reaction of acrylates with aromatic aldehydes,
      affording the desired MBH adducts with up to 90% ee. To gain mechanistic insights
      into the reaction, the effects of adding various additives on the MBH reaction
      were investigated. We propose that the hydrogen bonding interactions between the
      thiourea moiety of the catalyst and the enolate intermediate are crucial for the
      stereochemical outcome of the reaction. The method described in this report may
      provide a practical solution to the enantioselective MBH reaction of simple
      acrylates.

PMID- 21858322
TI  - Facile synthesis of pegylated zinc(II) phthalocyanines via transesterification
      and their in vitro photodynamic activities.
AB  - Treatment of 4,5-bis[4-(methoxycarbonyl)phenoxy]phthalonitrile and 4,5-bis[3,5
      bis(methoxycarbonyl)phenoxy]phthalonitrile with an excess of 1,3
      diiminoisoindoline in the presence of Zn(OAc)(2).2H(2)O and 1,8
      diazabicyclo[5.4.0]undec-7-ene in triethylene glycol monomethyl ether or
      polyethylene glycol monomethyl ether (with an average molecular weight of 550)
      led to "3 + 1" mixed cyclisation and transesterification in one pot, affording
      the corresponding di-beta-substituted zinc(II) phthalocyanines in 7-23% yield. As
      shown by absorption spectroscopy, these compounds were essentially non-aggregated
      in N,N-dimethylformamide and could generate singlet oxygen effectively. The
      singlet oxygen quantum yields (Phi(Delta) = 0.53-0.57) were comparable with that
      of the unsubstituted zinc(II) phthalocyanine (Phi(Delta) = 0.56). These compounds
      in Cremophor EL emulsions also exhibited photocytotoxicity against HT29 human
      colorectal adenocarcinoma and HepG2 human hepatocarcinoma cells with IC(50)
      values in the range of 0.25-3.72 MUM. The analogue with four triethylene glycol
      chains was the most potent photosensitiser and localised preferentially in the
      mitochondria of HT29 cells. The bis(polyethylene glycol)-counterpart could form
      surfactant-free nanoparticles both in water and in the culture medium. The
      hydrodynamic radii, as determined by dynamic laser light scattering, ranged from
      6.3 to 79.8 nm depending on the preparation methods and conditions. The
      photocytotoxicity of these nanoparticles (IC(50) = 0.43-0.56 MUM) was comparable
      with that of the Cremophor EL-formulated system (IC(50) = 0.34 MUM).

PMID- 21858323
TI  - Signaling of hypochlorous acid by selective deprotection of dithiane.
      [corrected].
AB  - The selective signaling of hypochlorous acid by dithiane-protected [corrected]
      pyrene-aldehyde was investigated. Dithiolane derivative of pyrene-aldehyde was
      efficiently deprotected by hypochlorous acid to its corresponding aldehyde, which
      resulted in a prominent UV-vis and turn-on type fluorescence signaling. The
      signaling was not affected by the presence of other common alkali, alkaline earth
      metal ions, and anions. Interference from Hg(2+) ions could be successfully
      circumvented by using Chelex-100 resin. Dithiane [corrected] also provided
      selectivity toward hypochlorous acid over other commonly used oxidant of hydrogen
      peroxide.

PMID- 21858324
TI  - Well-defined [Rh(NHC)(OH)] complexes enabling the conjugate addition of
      arylboronic acids to alpha,beta-unsaturated ketones.
AB  - The synthesis and catalytic activity of three well-defined monomeric rhodium(I)
      hydroxide complexes bearing N-heterocyclic carbene (NHC) ligands are reported.
      [Rh(cod)(ICy)(OH)] promoted the 1,4-addition of arylboronic acids to cyclic
      enones, with TONs and TOFs of 100,000 and 6,600 h(-1), respectively, at 0.001
      mol% catalyst loadings. Mechanistic studies permitted the isolation of a
      phenylrhodium intermediate.

PMID- 21858325
TI  - Extremely efficient and long lifetime fluorescence of cis-stilbene contained in a
      rigid dendrimer.
AB  - The fluorescence quantum yield of cis-stilbene-cored rigid polyphenylene
      dendrimer (cis-G2) is 20% even at room temperature. Moreover, the fluorescence
      lifetime of cis-G2 is twice as long as that of the corresponding trans-isomer.

PMID- 21858327
TI  - One-step synthesis of silver/dopamine nanoparticles and visual detection of
      melamine in raw milk.
AB  - In this work, we propose a simple, sensitive and reliable assay for melamine in
      raw milk with dopamine-stabilized silver nanoparticles (AgNPs) as a colorimetric
      reader. Dopamine can reduce Ag(+) and functionalize the produced AgNPs to form
      monodispersed AgNPs. The coexisting melamine in reaction solution could bind
      dopamine through Michael addition and Schiff base reactions, which leads to the
      aggregation of AgNPs and induces a colorimetric response. The one-step assay is
      simple, rapid and highly sensitive. The color-change is quantitatively correlated
      with the concentration of melamine in the range of 10 ppb to 1.26 ppm, which is
      below the safety limit in China (1.0 ppm) and EU (2.0 ppm). The coexisting
      substances including phenylalanine, dl-leucine, l-glutamate, sulfanilic acid,
      Mg(2+), galactose, lysine, urea and glucose do not affect the determination of
      melamine. The colorimetric sensor can be used for rapid monitoring of raw milk
      quality.

PMID- 21858328
TI  - Electrochemical behaviour and voltammetric sensitivity at arrays of nanoscale
      interfaces between immiscible liquids.
AB  - Arrays of nanoscale interfaces between immiscible electrolyte solutions were
      formed using silicon nitride nanopore array membranes. Nanopores in the range
      from 75 nm radius down to 17 nm radius were used to form the nano-interfaces. It
      was found that the liquid organic phase electrolyte solution filled the pores so
      that inlaid nano-interfaces were formed with the aqueous phase. Cyclic
      voltammetry at these nano-interface arrays demonstrated steady-state behaviour at
      the larger interfaces but the voltammetric wave-shape became progressively worse
      as the interface size decreased. It was found that the ion transfer currents were
      ca. 50% of those expected based on theoretical calculations, which is attributed
      to overlap of diffusion zones at adjacent nano-interfaces. Here, the separation
      between adjacent nano-interfaces was 20-times the interface radius. The
      analytical sensitivity for ion transfer from the aqueous to the 1,6
      dichlorohexane organic phase was estimated from calibration plots of current
      density versus concentration of aqueous tetraethylammonium cation. The
      sensitivity was in the range of 65 MUA cm(-2) MUM(-1) (at 75 nm radius
      interfaces) to 265 MUA cm(-2) MUM(-1) (at 17 nm radius interfaces). The
      sensitivity depended directly on the inverse of the nano-interface radius,
      implying that smaller interfaces will provide better sensitivity, due to the
      enhanced flux of analyte arising from convergent diffusion to smaller
      electrochemical interfaces.

PMID- 21858326
TI  - Activation of p38 MAP kinase and JNK pathways by UVA irradiation.
AB  - There are more than two million new cases of non-melanoma skin cancers (NMSCs)
      diagnosed each year in the United States of America. The clear etiological factor
      is chronic exposure to solar radiation from the sun. The wavelengths of solar
      light that reach the earth's surface include UVB (280-320 nm), which accounts for
      1-10%, and UVA (320-400 nm), which accounts for 90-99% of the radiation. While
      most published research has focused on the effects of UVB, little is known
      concerning UVA-mediated signal transduction pathways, and their role in skin
      tumor promotion and progression, giving rise to squamous cell carcinomas (SCCs).
      Here, we focus on UVA-mediated activation of p38 MAP kinase and c-Jun N-terminal
      kinase (JNK), and their roles in activator protein-1 (AP-1) mediated
      transcription, cyclooxygenase-2 (COX-2) and Bcl-XL expression. Since p38 MAP
      kinase and JNK play major roles in the expression of UVA-induced AP-1, COX-2 and
      Bcl-XL, pharmacological inhibitors of these kinases may be useful in the
      chemoprevention of SCC skin cancer.

PMID- 21858329
TI  - Synthesis and reactivity of a uranyl-imidazolyl complex.
AB  - Treatment of [UO(2)(Ar(2)nacnac)Cl](2) with 4 equiv. of Li(C(4)H(5)N(2)) results
      in the formation of a rare uranyl organometallic complex [Li(MeIm)][UO(MU
      O)(Ar(2)nacnac)(MU-C,N-C(4)H(5)N(2))(2)] (2), in moderate yield. Reaction of 2
      with 1 equiv. of MCl(2) (M = Fe, Co) yields the bimetallic complexes
      [MCl(MeIm)][UO(2)(Ar(2)nacnac)(MU-N,C-C(4)H(5)N(2))(2)] (M = Fe, 3; M = Co, 4).

PMID- 21858330
TI  - Charge transfer interactions between conjugated block copolymers and reduced
      graphene oxides.
AB  - The charge transfer interactions between reduced graphene oxides and conjugated
      block copolymers were confirmed by various spectroscopic methods, giving rise to
      manipulation of the electrical properties of the former.

PMID- 21858331
TI  - Anisotropic ionic liquids built from nonmesogenic cation surfactants and Keggin
      type polyoxoanions.
AB  - Non-mesogenic unit bearing Keggin-type polyoxoanions with tetra-n-octylammonium
      counterions exhibit an ionic liquid crystalline structure via ionic self-assembly
      in a certain temperature range.

PMID- 21858332
TI  - Direct spectroscopic evidence for binding of anastrozole to the iron heme of
      human aromatase. Peering into the mechanism of aromatase inhibition.
AB  - Aromatase (CYP19A1), is a microsomal cytochrome P450 catalysing the conversion of
      androgens to estrogens. Non-steroidal inhibitors, such as anastrozole, are
      important drugs in breast cancer therapy. Using hyperfine sublevel correlation
      (HYSCORE) spectroscopy we provide the first experimental evidence of the binding
      of anastrozole to the iron heme of human aromatase.

PMID- 21858333
TI  - Hole transport in sensitized CdS-NiO nanoparticle photocathodes.
AB  - A general chemical approach was used to synthesise NiO-CdS core-shell
      nanoparticle films as photocathodes for p-type semiconductor-sensitized solar
      cells. Compared to dye-sensitized NiO photocathodes, the CdS-sensitized NiO
      cathodes exhibited two orders of magnitude faster hole transport (attributable to
      the passivation of surface traps by the CdS) and almost 100% charge-collection
      efficiencies.

PMID- 21858334
TI  - MoO3 nanowires as electrochemical pseudocapacitor materials.
AB  - MoO(3) nanowires synthesized using a biomolecule-assisted hydrothermal approach
      showed excellent adsorption ability for the removal of RhB and were also shown to
      be excellent pseudocapacitor materials.

PMID- 21858335
TI  - Selective complexation of n-alkanes with pillar[5]arene dimers in organic media.
AB  - A pillar[5]arene dimer was synthesized by linking a mono-hydroxylated
      pillar[5]arene with 1,4-bis(bromomethyl)benzene. The pillar[5]arene dimer formed
      stronger complexes with n-alkanes than did a monomeric pillar[5]arene.

PMID- 21858336
TI  - Reliable structural, thermodynamic, and spectroscopic properties of organic
      molecules adsorbed on silicon surfaces from computational modeling: the case of
      glycine@Si(100).
AB  - Chemisorption of glycine on Si(100) has been studied by an integrated
      computational strategy based on perturbative anharmonic computations employing
      geometries and harmonic force fields evaluated by hybrid density functionals
      coupled to purposely tailored basis sets. It is shown that such a strategy allows
      the prediction of spectroscopic properties of isolated and chemisorbed molecules
      with comparable accuracy, paving the route toward a detailed analysis of surface
      induced changes of glycine vibrational spectra.

PMID- 21858337
TI  - Surface models and reaction barrier in Eley-Rideal formation of H2 on graphitic
      surfaces.
AB  - The exothermic, collinearly-dominated Eley-Rideal hydrogen formation on graphite
      is studied with electronic structure and quantum dynamical means. In particular,
      the focus is on the importance of the model used to describe the graphitic
      substrate, in light of the marked discrepancies present in available literature
      results. To this end, the collinear reaction is considered and the potential
      energy surface is computed for a number of different graphitic surface models
      using Density Functional Theory (DFT) for different dynamical regimes. Quantum
      dynamics is performed with wavepacket techniques down to the cold collision
      energies relevant for the chemistry of the interstellar medium. Results show that
      the reactivity at moderate-to-high collision energies sensitively depends on the
      shape of the PES in the entrance channel, which in turn is related to the adopted
      surface model. At low energies we rule out the presence of any barrier to
      reaction, thereby highlighting the importance of quantum reflection in limiting
      the reaction efficiency.

PMID- 21858339
TI  - Cobalt catalysts for the coupling of CO2 and epoxides to provide polycarbonates
      and cyclic carbonates.
AB  - This comprehensive tutorial review focuses on well-defined cobalt complexes that
      serve as homogeneous catalysts for the production of polycarbonates and cyclic
      carbonates from the coupling of carbon dioxide and epoxides. Special
      considerations are given to the mechanistic pathways involved in these processes.

PMID- 21858338
TI  - Nucleic acid amphiphiles: synthesis and self-assembled nanostructures.
AB  - This review provides an overview of a relatively new class of bio-conjugates, DNA
      amphiphiles, which consist of oligonucleotides covalently bonded to synthetic
      hydrophobic units. The reader will find the basic principles for the structural
      design and preparation methods of the materials. Moreover, the self-assembly into
      superstructures of higher order will be highlighted. Finally, some potential
      applications will be described.

PMID- 21858340
TI  - Mesoporous silicabis(ethylsulfanyl)propane palladium catalysts for hydrogenation
      and one-pot two-step Suzuki cross-coupling followed by hydrogenation.
AB  - The solid phase catalytic activity of mesoporous silicabis(ethylsulfanyl)propane
      palladium catalysts for hydrogenation and novel one-pot two-step Suzuki cross
      coupling followed by hydrogenation is described. The efficiency of catalytic
      hydrogenation was measured for substrate nitrobenzene with 5, 7 and 14 nm average
      pore diameter materials. The 5 nm pore material performed best and was also very
      effective in the catalytic hydrogenation of alkene, nitrile and imine substrates.
      Novel one-pot two-step Suzuki cross-coupling and hydrogenation was demonstrated
      using bromonitro- and bromodinitrobenzene and phenylboronic acid as substrates
      with conversion to the corresponding coupled amino compounds. As a consequence of
      the high affinity of the sulfur ligands for palladium, none was detected in
      leaching tests and the catalyst is easily separated and recycled.

PMID- 21858341
TI  - Variable coordination of amine functionalised N-heterocyclic carbene ligands to
      Ru, Rh and Ir: C-H and N-H activation and catalytic transfer hydrogenation.
AB  - Chelating amine and amido complexes of late transition metals are highly valuable
      bifunctional catalysts in organic synthesis, but complexes of bidentate amine-NHC
      and amido-NHC ligands are scarce. Hence, we report the reactions of a secondary
      amine functionalised imidazolium salt 2a and a primary-amine functionalised
      imidazolium salt 2b with [(p-cymene)RuCl(2)](2) and [Cp*MCl(2)](2) (M = Rh, Ir).
      Treating 2a with [Cp*MCl(2)](2) and NaOAc gave the cyclometallated compounds
      Cp*M(C,C)I (M = Rh, 3; M = Ir, 4), resulting from aromatic C-H activation. In
      contrast, treating 2b with [(p-cymene)RuCl(2)](2), Ag(2)O and KI gave the amine
      NHC complex [(p-cymene)Ru(C,NH(2))I]I (5). The reaction of 2b with [Cp*MCl(2)](2)
      (M = Rh, Ir), NaO(t)Bu and KI gave the amine-NHC complex [Cp*Rh(NH(2))I]I (6) or
      the amido-NHC complex Cp*Ir(C,NH)I (7); both protonation states of the Ir complex
      could be accessed: treating 7 with trifluoroacetic acid gave the amine-NHC
      complex [Cp*Ir(C,NH(2))I][CF(3)CO(2)] (8). These are the first primary amine- or
      amido-NHC complexes of Rh and Ir. Solid-state structures of the complexes 3-8
      have been determined by single crystal X-ray diffraction. Complexes 5, 6 and 7
      are pre-catalysts for the catalytic transfer hydrogenation of acetophenone to 1
      phenylethanol, with ruthenium complex 5 demonstrating especially high reactivity.

PMID- 21858343
TI  - Control of the transition temperatures of metallomesogens by specific interface
      design: application to Mn12 single molecule magnets.
AB  - Reaction of the Single Molecule Magnet [Mn(12)O(12)(CH(3)CO(2))(16)(H(2)O)(4)]
      (Mn(12)) with mesogenic dendritic ligands Li (i = 4, 5) quantitatively yields
      functional clusters [Mn(12)O(12)(Li-H)(16)(H(2)O)(4)] (i = 4, 5) that self
      organize into a thermotropic SmA-type liquid crystalline phase. The perturbation
      of the molecular interface by methylation of the terminal mesogenic cyanobiphenyl
      groups induces a significant decrease of the clearing temperature without
      affecting the magnetic properties and the supramolecular organization of the
      Mn(12)-based clusters.

PMID- 21858342
TI  - Copper(II) complexes of rat amylin fragments.
AB  - The fragments of rat amylin rIAPP(17-29) (Ac-VRSSNNLGPVLPP-NH(2)), rIAPP(17-22)
      (Ac-VRSSNN-NH(2)), rIAPP(19-22) (Ac-SSNN-NH(2)) and rIAPP(17-20) (Ac-VRSS-NH(2))
      together with the related mutant peptides (Ac-VASS-NH(2) and Ac-VRAA-NH(2)) have
      been synthesized and their copper(II) complexes studied by potentiometric, UV
      Vis, CD and EPR spectroscopic methods. Despite the lack of any common strongly
      coordinating donor functions some of these fragments are able to bind copper(II)
      ions in the physiological pH range. The longest fragment rat amylin(17-29) keeps
      one equivalent copper(II) ion in solution in the whole pH range, while two other
      peptides Ac-VRSSNN-NH(2) and Ac-SSNN-NH(2) are also able to interact with
      copper(II) ions in the slightly alkaline pH range. According to the spectral
      parameters of the complexes, the peptides can be classified into two different
      categories: (i) the tetrapeptides Ac-VRSS-NH(2), Ac-VASS-NH(2) and Ac-VRAA-NH(2)
      can interact with copper(II) only under strongly alkaline conditions (pH > 10.0)
      and the formation of only one species with four amide nitrogen coordination can
      be detected; (ii) the peptides Ac-VRSSNNLGPVLPP-NH(2), Ac-VRSSNN-NH(2) and Ac
      SSNN-NH(2) can form complexes above pH 6.0 with the major stoichiometries [CuH(
      2)L], [CuH(-3)L](-) and [CuH(-4)L](2-). These data support that rIAPP(17-29) can
      interact with copper(II) ions under physiological conditions and the SSNN
      tetrapeptide fragment can be considered as the shortest sequence responsible for
      metal binding. Density functional theory (DFT) calculations provide some
      information on the possible coordination modes of Ac-SSNN-NH(2) towards the
      copper(II) ion and suggest that for [CuH(-2)L], [CuH(-3)L](-) and [CuH(-4)L](2-),
      the binding of two, three and four deprotonated amide nitrogens, with NH(-) of
      the side chain of asparagine as anchoring group, is probable. Moreover, these
      data reveal that peptides can be effective metal binding ligands even in the
      absence of anchoring groups, if more polar side chains are present in a specific
      sequence.

PMID- 21858344
TI  - Targeted and multifunctional arene ruthenium chemotherapeutics.
AB  - The introduction of multifunctionalities for tumour targeting is becoming a
      popular strategy toward the development of new therapeutic agents. In particular,
      the multifaceted potential of ruthenium(II)-arene complexes show great promise as
      chemotherapeutics. An ever-increasing number of papers dealing with the
      integration of ruthenium complexes with biologically active molecules to derive
      bioorganometallic molecules of chemotherapeutic significance have been published
      in recent years. This perspective review presents a short overview of
      multifunctional ruthenium-based drugs, especially those containing arene
      ruthenium complexes, with the emphasis on the combination of photosensitizers
      with ruthenium complexes for the preparation of novel multifunctional
      photodynamic therapy agents.

PMID- 21858345
TI  - Accidentally on purpose: construction of a ferromagnetic, oxime-based [Mn(III)2]
      dimer.
AB  - The serendipitous self-assembly of the complex [Mn(III)(2)Zn(II)(2)(Ph-sao)(2)(Ph
      saoH)(4)(hmp)(2)] (1),whose magnetic core consists solely of two symmetry
      equivalent Mn(iii) ions linked by two symmetry equivalent -N-O- moieties,
      provides a relatively simple model complex with which to study the magneto
      structural relationship in oxime-bridged Mn(III) cluster compounds. Dc magnetic
      susceptibility measurements reveal ferromagnetic (J = +2.2 cm(-1)) exchange
      resulting in an S = 4 ground state. Magnetisation measurements performed at low
      temperatures and high fields reveal the presence of significant anisotropy, with
      ac measurements confirming slow relaxation of the magnetisation and Single
      Molecule Magnetism behaviour. Simulations of high field, high frequency EPR data
      reveal a single ion anisotropy, D((Mn(III))) = -3.83 cm(-1). DFT studies on a
      simplified model complex of 1 reveal a pronounced dependence of the exchange
      coupling on the relative twisting of the oxime moiety with respect to the metal
      ion positions, as suggested previously in more complicated [Mn(III)(3)] and
      [Mn(III)(6)] clusters.

PMID- 21858346
TI  - Enhanced charge storage by the electrocatalytic effect of anodic TiO2 nanotubes.
AB  - Ordered titania nanotube (TNT) arrays were fabricated by anodization of titanium
      with a very fast voltage ramp speed. Co(OH)(2)/TNT nanocomposite was synthesized
      by cathodic deposition using the as-anodized TNT as the substrate. Scanning
      electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy and X-ray
      photoelectron spectroscopy (XPS) were used to characterize the morphology,
      crystalline structure and chemical state. The capacitive characteristics were
      investigated by cyclic voltammetry (CV), charge-discharge tests, and
      electrochemical impedance spectroscopy (EIS). Thanks to the electrocatalytic
      effect of the as-anodized TNTs on the reduction of Co(OH)(2), the Co(OH)(2)/TNT
      composite electrode exhibits a significantly enhanced charge storage capacity (an
      increase of 73%) when compared with Co(OH)(2)/Ti (titanium as the deposition
      substrate). The occurrence of such an electrocatalytic effect is suggested to be
      related to the nano-sized TiO(2) crystals (rutile) embedded in organized
      amorphous TNTs. Co(OH)(2)/TNT demonstrates enhanced specific energy, high rate
      capability and good cyclability, and can be a potential electrode of choice for
      supercapacitors.

PMID- 21858347
TI  - Synthesis of well-dispersed layered double hydroxide core@ordered mesoporous
      silica shell nanostructure (LDH@mSiO2) and its application in drug delivery.
AB  - We demonstrate an efficient synthesis of novel layered double hydroxide
      mesoporous silica core-shell nanostructures (LDH@mSiO(2)) that have a hexagonal
      MgAl-LDH nanoplate core and an ordered mesoporous silica shell with
      perpendicularly oriented channels via a surfactant-templating method.
      Transmission electron microscopy, X-ray diffraction and N(2) sorption analyses
      confirmed that the obtained nanostructures have uniform accessible mesopores
      (~2.2 nm), high surface area (~430 m(2) g(-1)), and large pore volume (~0.22
      cm(3) g(-1)). Investigations of drug release and bio-imaging showed that this
      material has a slow release effect of ibuprofen and good biocompatibility. This
      work provides an economical approach to fabricate LDH@mSiO(2) core-shell
      nanostructures, which may have great potential in broad drug delivery and
      hyperthermia therapy applications.

PMID- 21858348
TI  - Practical and stereoselective synthesis of beta-amino sulfones from alkyl phenyl
      sulfones and N-(tert-butylsulfinyl) aldimines.
AB  - A practical and straightforward approach for the highly stereoselective synthesis
      of beta-amino sulfones was developed. With lithium bis(trimethylsilyl)amide as
      the base, the corresponding sulfone-stabilized carbanion derived from alkylphenyl
      sulfone can be transferred to N-(tert-butylsulfinyl) aldimines in excellent
      yields and with high diastereoselectivity.

PMID- 21858349
TI  - Photo-oxidation of proteins.
AB  - Photo-induced damage to proteins occurs via multiple pathways. Direct damage
      induced by UVB (lambda 280-320 nm) and UVA radiation (lambda 320-400 nm) is
      limited to a small number of amino acid residues, principally tryptophan (Trp),
      tyrosine (Tyr), histidine (His) and disulfide (cystine) residues, with this
      occurring via both excited state species and radicals. Indirect protein damage
      can occur via singlet oxygen ((1)O(2)(1)Delta(g)), with this resulting in damage
      to Trp, Tyr, His, cystine, cysteine (Cys) and methionine (Met) residues. Although
      initial damage is limited to these residues multiple secondary processes, that
      occur both during and after radiation exposure, can result in damage to other
      intra- and inter-molecular sites. Secondary damage can arise via radicals (e.g.
      Trp, Tyr and Cys radicals), from reactive intermediates generated by (1)O(2)
      (e.g. Trp, Tyr and His peroxides) and via molecular reactions of photo-products
      (e.g. reactive carbonyls). These processes can result in protein fragmentation,
      aggregation, altered physical and chemical properties (e.g. hydrophobicity and
      charge) and modulated biological turnover. Accumulating evidence implicates these
      events in cellular and tissue dysfunction (e.g. apoptosis, necrosis and altered
      cell signaling), and multiple human pathologies.

PMID- 21858350
TI  - Photodynamic inactivation of Penicillium chrysogenum conidia by cationic
      porphyrins.
AB  - This work reports the photophysical and biological evaluation of five cationic
      porphyrins as photosensitizers (PS) for the photodynamic inactivation (PDI) of
      Penicillium chrysogenum conidia. Two different cationic porphyrin groups were
      synthesized from 5,10,15,20-tetrakis(4-pyridyl)porphyrin and 5,10,15,20
      tetrakis(pentafluorophenyl)porphyrin. The photostability and singlet oxygen
      generation studies showed that these molecules are photostable and efficient
      singlet oxygen generators. PDI experiments of P. chrysogenum conidia conducted
      with 50 MUmol L(-1) of photosensitiser under white light at a fluence rate of 200
      mW cm(-2) over 20 min showed that the most effective PS caused a 4.1 log
      reduction in the concentration of viable conidia. The present results show that
      porphyrins 1a and 1b are more efficient PSs than porphyrin 2a while porphyrins 1c
      and 2b show no inactivation of P. chrysogenum. It is also clear that the
      effectiveness of the molecule as PS for antifungal PDI is strongly related with
      the porphyrin substituent groups, and consequently their solubility in
      physiological media. The average amount of PS adsorbed per viable conidium was a
      determining factor in the photoinactivation efficiency and varied between the
      different studied PSs. Cationic PSs 1a and 1b might be promising anti-fungal PDI
      agents with potential applications in phytosanitation, biofilm control,
      bioremediation, and wastewater treatment.

PMID- 21858351
TI  - Unusually efficient trans-to-cis photoisomerization of diphenylbutadiene
      dendrimers in water.
AB  - A diphenylbutadiene-cored dendrimer exhibited a remarkably high quantum yield for
      trans-to-cis photoisomerization in aqueous solution. Analysis of the fluorescence
      lifetimes and the wavelength-dependent excitation spectra suggested that the core
      butadiene adopts multiple conformations, one or several of which is sufficiently
      distorted to undergo preferential photoisomerization.

PMID- 21858352
TI  - A highly sensitive redox-active monolayer for "signal-on" optical detection of
      iron(II).
AB  - "Signal-on" optical detection of parts-per-billion (ppb) levels of Fe(II) in
      CH(2)Cl(2) and H(2)O was demonstrated using a redox-active and optically rich
      metal complex-based monolayer.

PMID- 21858353
TI  - Palladium-catalyzed hydroacyloxylation of ynamides.
AB  - In the presence of substoichiometric Pd(OAc)(2), carboxylic acids undergo highly
      regio- and stereoselective additions to ynamides to provide alpha
      acyloxyenamides.

PMID- 21858354
TI  - Weak Ag...Ag and Ag...pi interactions in templating regioselective single and
      double [2+2] reactions of N,N'-bis(3-(4-pyridyl)acryloyl)-hydrazine: synthesis of
      an unprecedented tricyclohexadecane ring system.
AB  - Synthesis of a stereospecific four-twelve-four fused tricyclic compound
      containing a tetraamide macrocycle has been achieved by the solid state [2+2]
      reaction through utilization of Ag...Ag interaction. The influence of anions on
      crystal packing has been utilized for the synthesis of a regioselective mono
      cyclobutane compound via the Ag...pi interactions.

PMID- 21858355
TI  - Simple and efficient nickel-catalyzed cross-coupling reaction of alkynylalanes
      with benzylic and aryl bromides.
AB  - Highly efficient and simple coupling reactions of benzylic and aryl bromides with
      aluminium acetylide catalyzed by NiCl(2)(PPh(3))(2) are reported. The coupling
      reactions proceed at room temperature employing 4 mol% catalyst, affording
      coupling products in excellent yields of up to 95% in short reaction times. The
      system worked efficiently with aryl and heterocyclic bromides as well.

PMID- 21858356
TI  - Dendron-mediated self-assembly of highly PEGylated block copolymers: a modular
      nanocarrier platform.
AB  - PEGylated dendron coils (PDCs) were investigated as a novel potential nanocarrier
      platform. PDCs self-assembled into micelles at lower CMCs than linear copolymer
      counterparts by 1-2 orders of magnitude, due to the unique architecture of
      dendrons. MD simulations also supported thermodynamically favourable self
      assembly mediated by dendrons.

PMID- 21858357
TI  - Studies on the interaction of achiral cationic pseudoisocyanine with chiral metal
      complexes.
AB  - The effect of chiral metal complexes ([Co(en)(3)]I(3).H(2)O, cis
      [CoBr(NH(3))(en)(2)]Br(2), K[Co(edta)].2H(2)O and [Ru(phen)(3)](PF(6))(2)) on the
      polymer-bound J-aggregates in aqueous mixtures of pesudoisocyanine (PIC) iodine
      and poly(acrylic acid, sodium)(PAAS) have been studied by UV-vis absorption,
      circular dichroism (CD) and fluorescence spectra. At low concentration, the PIC
      monomers could self-assemble to form supermolecules by binding to each of the
      COO(-) groups on the polymer chains through electrostatic interactions. After the
      addition of chiral metal complexes to the formed PIC-PAAS J-aggregates, we found
      that only the chiral multiple pi-conjugated phenanthroline metal complexes could
      transfer their metal-centered chiral information to the formed J-aggregates. The
      chiral J-aggregates showed a characteristic induced circular dichroism (ICD) in
      the visible region of J-band chromophore, and the ICD signals depend on the
      absolute configuration, concentration of the chiral multiple pi-conjugated metal
      complexes, as well as temperature. More interestingly, the supramolecular
      chirality of the polymer supported PIC J-aggregates could be memorized even after
      the addition of an excess opposite chiral complex enantiomers. This is in sharp
      contrast to the behavior in the high concentrated NaCl induced PIC-J aggregates,
      in which the optical rotation of a mixture of two enantiomers varies linearly
      with their ratio.

PMID- 21858358
TI  - Photophysical behavior of acridine with amines within the micellar
      microenvironment of SDS: a time-resolved fluorescence and laser flash photolysis
      study.
AB  - The photophysical behavior of acridine (Acr) shows a facilitated water assisted
      protonation equilibrium between its deprotonated (Acr* ~ 3.4 ns) and protonated
      forms (AcrH(+)* ~ 33 ns) within a confined environment of sodium dodecyl sulphate
      (SDS) micelles above the critical micellar concentration of 8 mM. The acidic
      interface of the micelles is capable of protonating Acr whereas deprotonated Acr
      is partitioned into the hydrophobic core. The time-resolved-area-normalized
      emission spectra confirm the presence of both Acr* and AcrH(+)*, while time
      resolved-emission spectra depict time evolution between them. Quenching of
      AcrH(+)* with triethylamine (TEA) results in a linear Stern-Volmer (S-V) plot,
      whereas non-linearity arises with N,N-dimethylaniline (DMA). Both steady-state
      and time-resolved quenching results with TEA are explained on the basis of
      excited state proton transfer (ESPT), however the reasons behind the quenching of
      excited Acr with DMA are proposed as ESPT followed by a photoinduced electron
      transfer. Partitioning of DMA at the interface makes it accessible for both Acr*
      and AcrH(+)* in hydrophobic and hydrophilic regions of micelles respectively. The
      rate of electron transfer at the interface is found to be slower compared to that
      in the hydrophobic core. Characterization of transient intermediates formed
      during ESPT and PET between Acr and amines by laser-flash photolysis also
      supports the observation obtained during fluorescence studies. The mode of
      interactions between Acr and amines inside micelles is controlled by the
      localization of the proton/electron donors and acceptors in different hydrophobic
      or hydrophilic regions of such nano-confined environments.

PMID- 21858359
TI  - Understanding the polarity of ionic liquids.
AB  - The polarities of a wide range of ionic liquids have been determined using the
      Kamlet-Taft empirical polarity scales alpha, beta and pi*, with the dye set
      Reichardt's Dye, N,N-diethyl-4-nitroaniline and 4-nitroaniline. These have been
      compared to measurements of these parameters with different dye sets and to
      different polarity scales. The results emphasise the importance of recognising
      the role that the nature of the solute plays in determining these scales. It is
      particularly noted that polarity scales based upon charged solutes can give very
      different values for the polarity of ionic liquids compared to those based upon
      neutral probes. Finally, the effects of commonplace impurities in ionic liquids
      are reported.

PMID- 21858360
TI  - UV-induced growth of cyanopolyyne chains in cryogenic solids.
AB  - UV laser excitation of cryogenic solids doped with cyanoethyne, HC(3)N, led to an
      in situ creation of longer carbon-nitrogen chains, namely HC(5)N, C(4)N(2), and
      C(6)N(2), heralded by their strong visible luminescence. HC(5)N and C(4)N(2)
      molecules can form, most probably, within HC(3)N aggregates linked by hydrogen
      bonds, while the reaction occurring between two isolated, photochemically created
      C(3)N radicals yields C(6)N(2). This latter species, dicyanobutadiyne, is easily
      detected in Ar, Kr, N(2), as well as in parahydrogen solids. The C(6)N(2)
      phosphorescence is identified here for the first time. The reported carbon chain
      coupling reactions in rigid environments are of interest for astrochemistry of
      interstellar ices.

PMID- 21858361
TI  - Remarkable nanoconfinement effects on chemical equilibrium manifested in
      nucleotide dimerization and H-D exchange reactions.
AB  - Nanoconfinement entropic effects on chemical equilibrium involving a small number
      of molecules, which we term NCECE, are revealed by two widely diverse types of
      reactions. Employing statistical-mechanical principles, we show how the NCECE
      effect stabilizes nucleotide dimerization observed within self-assembled
      molecular cages. Furthermore, the effect provides the basis for dimerization even
      under an aqueous environment inside the nanocage. Likewise, the NCECE effect is
      pertinent to a longstanding issue in astrochemistry, namely the extra deuteration
      commonly observed for molecules reacting on interstellar dust grain surfaces. The
      origin of the NCECE effect is elucidated by means of the probability
      distributions of the reaction extent and related variations in the reactant
      product mixing entropy. Theoretical modelling beyond our previous preliminary
      work highlights the role of the nanospace size in addition to that of the
      nanosystem size, namely the limited amount of molecules in the reaction mixture.
      Furthermore, the NCECE effect can depend also on the reaction mechanism, and on
      deviations from stoichiometry. The NCECE effect, leading to enhanced, greatly
      variable equilibrium "constants", constitutes a unique physical-chemical
      phenomenon, distinguished from the usual thermodynamical properties of
      macroscopically large systems. Being significant particularly for weakly
      exothermic reactions, the effects should stabilize products in other closed
      nanoscale structures, and thus can have notable implications for the growing
      nanotechnological utilization of chemical syntheses conducted within confined
      nanoreactors.

PMID- 21858363
TI  - Analytical theory of the catalytic mechanism in square wave voltammetry at disc
      electrodes.
AB  - A simple analytical expression is presented for the study of the first-order
      catalytic mechanism using Square Wave Voltammetry (SWV) at disc electrodes. These
      electrodes are extensively used in electrochemical studies but modelling the
      electrochemical response at this geometry is complex and usually requires the use
      of sophisticated numerical methods. By contrast, the analytical solution
      presented in this work is easy to compute and it is applicable to any size of the
      disc and for arbitrary kinetics of the catalytic reaction. The effects of the
      electrode size, the homogeneous rate constants, the frequency and the square wave
      amplitude on the SWV response are analyzed. Criteria are given for the detection
      of the steady-state response as well as procedures for the extraction of the
      catalytic rate constant from the value of the peak current. The theory is applied
      to obtain the kinetics of the reduction of the anion nitrite by an
      electrogenerated heteropolyanion [P(W(3)O(10))(4)](4-) at gold microdiscs.

PMID- 21858362
TI  - pH sensing using boron doped diamond electrodes.
AB  - The boron doped diamond (BDD) electrode is presented as an appropriate candidate
      for next generation glass-free, highly stable and accurate pH sensors. The method
      used in this study is based on the potential change related to the hydrogen
      evolution reaction following a current step, which is pH dependent. Alkali
      cations in the solution have no influence on the accuracy of the pH calibration
      curve, which provides an advantage with respect to the conventional pH glass
      electrode. The unwanted influence of electrochemically active compounds in
      solution can be avoided by adjusting the current density applied during
      chronopotentiometric measurements. The accuracy of the pH measurements is due to
      the excellent stability as well as the wide potential window and low background
      current of BDD electrodes. This faculty was not observed when using conventional
      electrode materials. The efficacy of this new type of pH sensor has been tested
      using tap water as a typical real sample.

PMID- 21858364
TI  - A colorimetric selective sensing probe for calcium ions with tunable dynamic
      ranges using cytidine triphosphate stabilized gold nanoparticles.
AB  - Cytidine triphosphate (CTP) stabilized-Au nanoparticles (CTP-AuNPs) allow a
      quantitative assay of Ca(2+) down to a concentration of 10(-4) M with high
      selectivity towards Ca(2+) ions over various metal ions including Mg(2+) and the
      detection range of this probe also can be easily tuned by changing the
      concentration of CTP.

PMID- 21858365
TI  - Ti/Pd-promoted intramolecular Michael-type addition of allylic carboxylates to
      activated alkenes.
AB  - An interesting protocol for the synthesis of different vinyl substituted carbo-
      and heterocycles based on a new intramolecular Michael-type reaction using
      allylic carboxylates as pronucleophiles is reported. The success of the catalytic
      process is based on the excellent cooperation between the late transition metal
      (palladium) and the radical reagent (titanium).

PMID- 21858366
TI  - Adsorption energetics of CO on supported Pd nanoparticles as a function of
      particle size by single crystal microcalorimetry.
AB  - The heat of adsorption and sticking probability of CO on well-defined Pd
      nanoparticles were measured as a function of particle size using single crystal
      adsorption microcalorimetry. Pd particles of different average sizes ranging from
      120 to 4900 atoms per particle (or from 1.8 to 8 nm) and Pd(111) were used that
      were supported on a model in situ grown Fe(3)O(4)/Pt(111) oxide film. To
      precisely quantify the adsorption energies, the reflectivities of the
      investigated model surfaces were measured as a function of the thickness of the
      Fe(3)O(4) oxide layer and the amount of deposited Pd. A substantial decrease of
      the binding energy of CO was found with decreasing particle size. Initial heat of
      adsorption obtained on the virtually adsorbate-free surface was observed to be
      reduced by about 20-40 kJ mol(-1) on the smallest 1.8 nm sized Pd particles as
      compared to the larger Pd clusters and the extended Pd(111) single crystal
      surface. This effect is discussed in terms of the size-dependent properties of
      the Pd nanoparticles. The CO adsorption kinetics indicates a strong enhancement
      of the adsorbate flux onto the metal particles due to a capture zone effect,
      which involves trapping of adsorbates on the support and diffusion to metal
      clusters. The CO adsorption rate was found to be enhanced by a factor of ~8 for
      the smallest 1.8 nm sized particles and by ~1.4 for the particles of 7-8 nm size.

PMID- 21858367
TI  - Fast oxygen exchange kinetics of pore-free Bi(1-x)Sr(x)FeO(3-delta) thin films.
AB  - The oxygen incorporation/extraction kinetics of the potential solid oxide fuel
      cell (SOFC) cathode material Bi(1-x)Sr(x)FeO(3-delta) with x = 0.5 and 0.8 was
      studied by electrochemical impedance spectroscopy on geometrically well-defined
      pore-free thin film electrodes. The oxygen exchange rate was found to be higher
      than that of La(1-x)Sr(x)FeO(3-delta) and-among cobalt-free perovskites-only
      surpassed by Ba(1-x)Sr(x)FeO(3-delta) which is however known to be unstable in a
      SOFC environment.

PMID- 21858368
TI  - Base-free two-step synthesis of 1,3-diketones and beta-ketoesters from alpha
      diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes.
AB  - We describe a convergent, base-free two-step synthesis of 1,3-diketones and beta
      ketoesters from alpha-diazocarbonyl compounds, trialkylboranes, and aromatic
      aldehydes in a three-component process. The synthetic potential of this protocol
      was underscored by the synthesis of several symmetrical 1,3,5-triaryl-4-alkyl and
      1,3,4,5-tetraryl substituted pyrazoles in a three-step sequence.

PMID- 21858369
TI  - A one-dimensional coordination polymer exhibiting simultaneous spin-crossover and
      semiconductor behaviour.
AB  - A rare organosulfur one-dimensional coordination polymer, [Co(C(9)H(6)NS)(2)],
      was synthesized by the reaction between the 8-mercaptoquinoline and cobalt
      acetate salts in EtOH, which shows strong magnetic coupling and the presence of
      spin-glassy and spin-crossover phenomena with simultaneous semiconductor
      behaviour.

PMID- 21858370
TI  - Retention of palladium and phosphine ligands using nanoporous
      polydicyclopentadiene thimbles.
AB  - Thimbles composed of polydicyclopentadiene retained Pd and phosphines used in
      Buchwald-Hartwig and Sonogashira coupling reactions but allowed the products to
      permeate. The products were isolated in high yields on the exteriors of the
      thimbles with no detectable contamination from phosphine and with Pd loadings as
      low as < 5.5 ppm.

PMID- 21858371
TI  - Ammonia plasma modification towards a rapid and low temperature approach for
      tuning electrical conductivity of ZnO nanowires on flexible substrates.
AB  - Though the fabrication of ZnO nanostructures is economical and low temperature,
      the lack of a facile, reliable and low temperature methodology to tune its
      electrical conductivity has prevented it from competing with other
      semiconductors. Here, we carried out surface modification of ZnO nanowires using
      ammonia plasma with no heat treatment, and studied their electrical properties
      over an extended time frame of more than a year. The fabrication of flexible
      devices was demonstrated via various methods of transferring and aligning as
      synthesized ZnO nanowires onto plastic substrates. Hall measurements of the
      plasma modified ZnO nanowires revealed p-type conductivity. The N1s peak was
      present in the X-ray photoelectron spectrum of the surface modified ZnO, showing
      the presence of ammonia complexes. Low temperature photoluminescence showed
      evidence of acceptor-bound exciton emission. The resulting electrical devices, a
      chemical sensor and p-n homojunction, show the tunable electrical response of the
      surface modified ZnO nanowires.

PMID- 21858372
TI  - Self-templated synthesis and thermal conductivity investigation for ultrathin
      perovskite oxide nanowires.
AB  - The large thermal conductivity of bulk complex metal oxides such as SrTiO(3),
      NaCo(2)O(4), and Ca(3)Co(4)O(9) has set a barrier for the improvement of
      thermoelectric figure of merit and the applications of these materials in high
      temperature (>=1000 K) thermoelectric energy harvesting and solid-state cooling.
      Here, we present a self-templated synthesis approach to grow ultrathin SrTiO(3)
      nanowires with an average diameter of 6 nm in large quantity. The thermal
      conductivity of the bulk pellet made by compressing nanowire powder using spark
      plasma sintering shows a 64% reduction in thermal conductivity at 1000 K, which
      agrees well with theoretical modeling.

PMID- 21858373
TI  - The interaction of lipid modified pseudopeptides with lipid membranes.
AB  - We have studied the structure of two lipopeptides based on the simple dipeptide
      building block L-Phe-D-Oxd. These peptides have been reported previously to form
      fiber-like materials. The lipopeptides synthesized here had the structures
      C(n)(2)H((2n+1))CO-L-Phe-D-Oxd-OBn or C(n)(2)H((2n+1))CO-D-Phe-L-Oxd-OBn with n =
      5 or 11. Addition of the N-terminal lipid modification did not cause a major
      disturbance of the structures these molecules form. The lipid modifications
      themselves showed highly rigid structures as inferred from solid-state (2)H NMR.
      The peptide backbone showed (13)C NMR chemical shifts in agreement with beta
      sheet secondary structure. Addition of a lipid modification to the N-terminus is
      a common motif in biology to attach proteins to the membrane. Therefore, we also
      investigated the lipopeptides in the presence of synthetic POPC bilayers. Two
      different molecular species were detected under these circumstances: (i)
      lipopeptide monomers that showed chain order parameters similar to those of the
      host membrane, (ii) lipopeptide aggregates that exhibited very similar structures
      and dynamics as the crystalline aggregates. Overall, the lipopeptides showed a
      well defined and rigid secondary structure that is in agreement with fibrillar
      aggregates previously detected for those peptides without the lipid modification.

PMID- 21858374
TI  - Nanoparticle labelling-based magnetic immunoassay on chip combined with
      electrothermal vaporization-inductively coupled plasma mass spectrometry for the
      determination of carcinoembryonic antigen in human serum.
AB  - A sensitive and selective on chip magnetic immunoassay method, based on a
      sandwich-type immunoreaction with PbS nanoparticle (NPs) labels in combination
      with electrothermal vaporization-inductively coupled plasma mass spectrometry
      (ETV-ICP-MS), was proposed for the determination of carcinoembryonic antigen
      (CEA). We designed and fabricated a microfluidic chip for magnetic immunoassay,
      and the prepared iminodiacetic acid modified silica coated magnetic nanoparticles
      (IDA-SCMNPs) were packed into the central microchannel to form a solid phase
      column by self-assembly under the magnetic field. After completion of the
      immunoreaction involving a primary antibody, CEA and a secondary antibody labeled
      with PbS NPs on a magnetic solid phase packed-column, ETV-ICP-MS was used to
      determine the concentration of Pb that was released from the captured PbS NPs
      using an acid-dissolution step. The concentrations of CEA can be correlated with
      that of Pb. The established method demonstrated a limit of detection of 0.058 MUg
      L(-1) for CEA, with a relative standard deviation (RSD) of 6.7% (c = 10 MUg L(
      1), n = 7). A linearity ranging from 0.2 MUg L(-1) to 50 MUg L(-1) and a 2-fold
      enrichment factor (from 60 MUL sample solution to 30 MUL eluent) were achieved.
      The proposed method was further validated by analyzing CEA in human serum. The
      results were in good agreement with those obtained by chemiluminescent
      immunoassay, which is currently used as a clinical method. Overall, this method
      offers the advantages of high speed, high sensitivity, high selectivity, low
      sample/reagents consumption, high integrity and versatility. Moreover, it can be
      easily applied to other biological and medical assays.

PMID- 21858375
TI  - cis-Glyco-fused benzopyran compounds as new amyloid-beta peptide ligands.
AB  - A small library of glyco-fused benzopyran compounds has been synthesised. Their
      interaction features with Abeta peptides have been characterised by using STD-NMR
      and trNOESY experiments. The conformational analysis of the compounds has also
      been carried out through molecular mechanics (MM) and molecular dynamics (MD)
      simulations.

PMID- 21858376
TI  - Development of a coarse-grained model for simulations of tridecanoin liquid-solid
      phase transitions.
AB  - Novel coarse-grained models for molecular dynamics of tridecanoin melts are here
      proposed as results of a coarse-graining step procedure. The procedure is
      implemented to develop three coarse-grained models of increasing number of
      particle types from two to four. Force fields are computed by minimization of the
      deviations of appropriate distribution functions of the coarse-grained models
      from those of a reference atomistic one. Density, diffusivity and shear viscosity
      are computed by numerical simulation and compared with experimental values. The
      ability of each model to describe liquid-solid transitions is also analyzed. In
      particular, the model with four types of coarse-grained beads shows a transition
      from a liquid to a crystal phase.

PMID- 21858377
TI  - Oxide nanocrystal based nanocomposites for fabricating photoplastic AFM probes.
AB  - We report on the synthesis, characterization and application of a novel
      nanocomposite made of a negative tone epoxy based photoresist modified with
      organic-capped Fe(2)O(3) nanocrystals (NCs). The mechanical properties of the
      nanocomposite drastically improve upon incorporation of a suitable concentration
      of NCs in the polymer, without deteriorating its photolithography performance.
      High aspect ratio 3D microstructures made of the nanocomposite have been
      fabricated with a uniform surface morphology and with a resolution down to few
      micrometres. The embedded organic-capped Fe(2)O(3) NCs drastically increase the
      stiffness and hardness of the epoxy based photoresist matrix, making the final
      material extremely interesting for manufacturing miniaturized polymer based
      mechanical devices and systems. In particular, the nanocomposite has been used as
      structural material for fabricating photoplastic Atomic Force Microscopy (AFM)
      probes with integrated tips showing outstanding mechanical response and high
      resolution imaging performance. The fabricated probes consist of straight
      cantilevers with low stress-gradient and high quality factors, incorporating
      sharp polymeric tips. They present considerably improved performance compared to
      pure epoxy based photoresist AFM probes, and to commercial silicon AFM probes.

PMID- 21858378
TI  - Total synthesis of the proposed structures of the DNA methyl transferase
      inhibitors peyssonenynes, and structural revision of peyssonenyne B.
AB  - The purported structures of the peyssonenynes A and B isolated from Peyssonnelia
      caulifera, and considered to be geometric isomers at the acetoxyenediyne moiety,
      have been synthesized. The E and Z geometries of the synthetic compounds were
      secured by the magnitude of the (3)J(H9-C7) values measured using the EXSIDE band
      variant of the gradient HSQC pulse sequence and by the chemical shifts of C(6).
      Comparison of the NMR data of the synthetic and natural products revealed that
      only those of the Z isomers matched, which correspond to peyssonenyne A. Using
      HPLC analysis it was found that peyssonenyne B must correspond to the sn-2
      positional isomer of the Z sn-1/3 counterpart. The four synthetic sn-1/3
      diastereomers are roughly equipotent as DNMT1 inhibitors when evaluated on a
      radioactive methyl transfer enzymatic assay after immunoprecipitation from K562
      human leukemia cells with anti-DNMT1 antibody.

PMID- 21858379
TI  - Amphiphilic allylation of arylidene-1,3-oxazol-5(4H)-one using bis-pi
      allylpalladium complexes: an approach to synthesis of cyclohexyl and cyclohexenyl
      alpha-amino acids.
AB  - An efficient method for synthesis of cyclohexyl and cyclohexenyl alpha-amino
      acids via palladium-catalyzed three-component assemblies followed by ring-closing
      metathesis (RCM) is described. The present catalytic reaction is successfully
      extended to substituted benzylidene azlactones 2a-j RCH=(1,3-oxazole): R = alkyl
      or aryl. The amphiphilic bis-allylation of these substrates has been achieved by
      replacing toxic allylstannanes with allyltrifluoroborate and the reaction
      proceeded smoothly to afford the corresponding 1,7-diene derivatives 3a-j in
      acceptable to good yields. RCM of the resulting octadienes using the first
      generation Grubbs catalyst gave easy access to stereodefined substituted
      cyclohexene derivatives 7-11 in high yields. Acid hydrolysis of the oxazolone
      ring of 7-10 gave protected amino acids 12-16. Debenzoylation of 13 and 15
      afforded 1-amino-6-aryl-cyclohex-3-enecarboxylic acids 17 and 18 in excellent
      yields, respectively. Moreover, catalytic reduction of 13 gave the corresponding
      cyclohexane derivative 19 which could be debenzoylated to give 1-amino-2
      phenylcyclohexene-1-carboxylic acid (20). The structures of compounds 9, 12 and
      13 were confirmed by X-ray structural analysis. It is an excellent method for
      creating a wide range of cyclic alpha,alpha-disubstituted alpha-amino acids.

PMID- 21858380
TI  - Rapid and ultrasensitive E. coli O157:H7 quantitation by combination of
      ligandmagnetic nanoparticles enrichment with fluorescent nanoparticles based two
      color flow cytometry.
AB  - A novel, fast and sensitive determination strategy for E. coli O157:H7 has been
      developed by combination of ligandmagnetic nanoparticles (LMNPs) enrichment with
      a fluorescent silica nanoparticles (FSiNPs) based two-color flow cytometry assay
      (LMNPs@FSiNPs-FCM). E. coli O157:H7 was first captured and enriched through the
      lectin concanavalin A (Con A) favored strong adhesion of E. coli O157:H7 to the
      mannose-conjugated magnetic nanoparticles. The enriched E. coli O157:H7 was
      further specially labeled with goat anti-E. coli O157:H7 antibody modified RuBpy
      doped FSiNPs, and then stained with a nucleic acid dye SYBR Green I (SYBR-I).
      After dual-labeling with FSiNPs and SYBR-I, the enriched E. coli O157:H7 was
      determined using multiparameter FCM analysis. With this method, the detection
      sensitivity was greatly improved due to the LMNPs enrichment and the signal
      amplification of the FSiNPs labelling method. Furthermore, the false positives
      caused by aggregates of FSiNPs conjugates and nonspecific binding of FSiNPs to
      background debris could be significantly decreased. This assay allowed the
      detection of E. coli O157:H7 in PB buffer at levels as low as 7 cells mL(-1). The
      total assay time including E. coli O157:H7 sample enrichment and detection was
      less than 4 h. An artificially contaminated bottled mineral water sample with a
      concentration of 6 cells mL(-1) can be detected by this method. It is believed
      that the proposed method will find wide applications in biomedical fields
      demanding higher sensitive bacterial identification.

PMID- 21858381
TI  - SERS from two-tier sphere segment void substrates.
AB  - Sphere segment void, or inverse opal, films prepared from a variety of coinage
      metals have shown promise as reliable and reproducible substrates for surface
      enhanced Raman spectroscopy (SERS). Sphere segment void substrates are prepared
      from colloidal templates consisting of one or more layers of polystyrene spheres.
      In this paper, we investigate the reflection spectra and SERS for a gold film
      consisting of two-tiers of spherical cavities, and show that the best SERS
      enhancements are obtained from substrates consisting of just a single layer of
      sphere segment voids.

PMID- 21858382
TI  - Speciation of oxaliplatin adducts with DNA nucleotides.
AB  - This paper describes a set of fast and selective high performance liquid
      chromatography (HPLC) methods coupled to electro-spray ionisation linear ion trap
      mass spectrometry (ESI-MS), sector-field inductively coupled plasma mass
      spectrometry (SF-ICP-MS) and UV detection for in vitro studies of the
      bifunctional adducts of oxaliplatin with mono-nucleotides, di-nucleotides and
      cellular DNA. The stationary phases and the optimised conditions used for each
      separation are discussed. Interaction of oxaliplatin with A and G mono
      nucleotides resulted in the formation of five bifunctional platinum
      diaminocyclohexane (DACHPt) adducts. These were two isomers of the A-DACHPt-A and
      A-DACHPt-G adducts, and one G-DACHPt-G adduct, as confirmed by MS/MS spectra
      obtained by collision induced dissociation. These adducts were also characterised
      by UV absorption data and SF-ICP-MS elemental (195)Pt and (31)P signals. Further,
      interaction of oxaliplatin with AG and GG di-nucleotides resulted in the
      formation of three adducts: DACHPt-GG and two isomers of the DACHPt-AG adduct, as
      confirmed by ESI-MS and the complementary data obtained by UV and SF-ICP-MS.
      Finally, a very sensitive LC-ICP-MS method for the quantification of oxaliplatin
      GG intra-strand adducts (DACHPt-GG) was developed and used for monitoring the in
      vitro formation and repair of these adducts in human colorectal cancer cells. The
      method detection limit was 0.14 ppb Pt which was equivalent to 0.22 Pt adduct per
      10(6) nucleotides based on a 10 MUg DNA sample. This detection limit makes this
      method suitable for in vivo assessment of DACHPt-GG adducts in patients
      undergoing oxaliplatin chemotherapy.

PMID- 21858383
TI  - Treatment of subaortic stenosis in hearts with single-ventricle physiology.
AB  - BACKGROUND: We evaluated the patients who had had a Damus-Kaye-Stansel (DKS)
      operation for single-ventricular physiology with the aorta originating from a
      hypoplastic ventricle and the pulmonary artery from the systemic ventricle.
      METHODS: Seven patients who were operated on between May 2007 and November 2010
      were evaluated retrospectively. The patients had been diagnosed with a transposed
      double-inlet left ventricle and triscuspid atresia, and  had  been  waiting for a
      Fontan operation. Systemic outflow stenosis was defined echocardiographically as
      those with a gradient greater than 20 mmHg, and angiographically those with
      greater than 5 mmHg in the subaortic region. RESULTS: The mean age and weight of
      the patients was 15 +/- 9.7 months and 8 +/- 3.3 kg, respectively. The mean
      gradient between the systemic ventricle and the aorta was 35 +/- 25 mmHg. This
      gradient decreased to 14.3 +/- 4 mmHg postoperatively. The early hospital
      mortality was 14% (one patient). The mean extubation time and mean time in the
      intensive care unit (ICU) were 13 +/- 7.3 hours and 2.2 +/- 0.5 days,
      respectively. The mean follow-up time was 11 +/- 2 months. No mortality and semi
      lunar valve insufficiency were observed after discharge. CONCLUSIONS: One of the
      major problems that occur while waiting for a Fontan operation is systemic
      ventricular hypertrophy and deterioration in the compliance of the ventricle due
      to systemic ventricular outflow stenosis. When the disadvantages of outflow
      resection are encountered, a DKS proves to be a good alternative.

PMID- 21858384
TI  - Pigment epithelium-derived factor inhibits high glucose induced oxidative stress
      and fibrosis of cultured human glomerular mesangial cells.
AB  - OBJECTIVE: To evaluate whether pigment epithelium-derived factor (PEDF) could
      prevent human mesangial cells (HMCs) from elevated glucose-induced oxidative
      stress and fibrosis. METHODS: The study took place in the Endocrinology
      Laboratory of Renmin Hospital of Wuhan University, Wuhan, China from December
      2009 to June 2010. The HMCs were treated with different concentrations of
      dextroglucose (5.6, 15, and 30 mmol/l), and 5.6 mmol/l D-glucose+24.4 mmol/l D
      mannitol (osmotic control) for 24 and 48 hours. To examine the beneficial effect
      of PEDF, HMCs were also incubated with high glucose (30 mmol/L) in the presence
      of different concentrations of PEDF (5, 10, 40, 100, and 160 nmol/l) for 48
      hours. RESULTS: The PEDF significantly inhibited the overexpression of
      transforming growth factor-beta 1, and extracellular matrix proteins (fibronectin
      and collagen IV) induced by the elevated glucose in HMCs. The PEDF also impeded
      high glucose-induced reactive oxygen species generation in HMCs. CONCLUSION:
      These results suggest that PEDF by virtue of its anti-oxidative and anti
      fibrogenic properties may have a therapeutic potential in diabetic nephropathy.

PMID- 21858385
TI  - Lung functions in poorly controlled type 1 Saudi diabetic children and
      adolescents.
AB  - OBJECTIVE: To determine the lung function among Saudi type 1 diabetes mellitus
      (T1DM) children and adolescents. METHODS: This study was conducted in the
      Department of Pediatrics, Division of Pediatric Pulmonology and University
      Diabetes Centre, College of Medicine, King Saud University, Riyadh, Kingdom of
      Saudi Arabia from December 2008 to July 2010. A group of 52 (26 male and 26
      female) volunteer T1DM children were recruited with an age range from 8-14 years
      (mean 12.05 +/- 1.42 years), mean duration of disease of 5.25 +/- 0.47 years, and
      mean glycosylated hemoglobin of 11.27 +/- 0.31%. Spirometry was performed on an
      Electronic Spirometer (Compact Vitalograph, Stockwell, London, UK). RESULTS:
      Pulmonary function in children with diabetes showed significant lower mean values
      of actual lung function parameters forced vital capacity (FVC), peak expiratory
      flow (PEF), and maximum mid expiratory flow rate (MMEF) compared to their
      predicted values. However, there was no significant reduction in the actual
      forced expiratory volume in the first second (FEV1), and FEV1/FVC% compared to
      their predicted values. CONCLUSION: The actual lung function data among Saudi
      T1DM children and adolescents showed significantly lower values of FVC, PEF, and
      MMEF compared to the predicted lung function data.

PMID- 21858386
TI  - The predictive value of serum mannan-binding lectin levels for diabetic control
      and renal complications in type 2 diabetic patients.
AB  - OBJECTIVE: To evaluate the predictability of estimation of serum mannan-binding
      lectin (MBL) for the presence of infectious complications in type 2 diabetes
      mellitus (T2DM) and its relation to the extent of diabetes control. METHODS: A
      comparative cross-sectional study was conducted at the Departments of Clinical
      Pathology and Internal Medicine, Faculty of Medicine, Benha University, Benha,
      Egypt from October 2009 to December 2010. Sixty adult patients with T2DM were
      divided into 2 groups: Group B and Group C and Group A as the control group. All
      subjects evaluation of insulin sensitivity (Homeostasis Model Assessment of
      Insulin Resistance [HOMA-IR]), and blood samples for estimation of fasting blood
      glucose (FBG), glycosylated hemoglobin A1c (HbA1c) and serum insulin, urea,
      creatinine, C-reactive protein (CRP), and MBL. RESULTS: All patients had
      significantly increased FBG, serum insulin, HOMA-IR index, serum CRP and MBL
      levels compared with the control group, with significantly higher levels in Group
      C. Levels of HbA1c, serum urea, and creatinine were significantly higher in
      patients than controls. There was a positive significant correlation between
      serum MBL and FBG, HOMAIR index, serum urea, creatinine, and CRP levels. The
      receiver operating characteristics curve analysis in infectious cases revealed
      high FBG, HOMA-index and serum levels of HbA1c, CRP, and MBL, while regression
      analysis defined elevated serum MBL levels as a significant independent predictor
      for the presence of infection. CONCLUSION: Elevated serum MBL in T2DM patients
      indicated a possible poor diabetic control and bad progression of the disease
      with possibility of the presence, or development of diabetic nephropathy
      especially in combination with elevated serum CRP.

PMID- 21858387
TI  - An extract from date seeds having a hypoglycemic effect. Is it safe to use?
AB  - OBJECTIVE: To investigate the safety of date seed extract administration, and to
      compare between toxic effects of diabetes on rats treated with insulin versus
      rats treated with insulin-seed extract. METHODS: This study was performed in the
      Anatomy Department, College of Medicine, King Saud University, Riyadh, Kingdom of
      Saudi Arabia from August to December 2010. One hundred rats were divided into 5
      groups. Group 1 served as control. Group 2 was given daily ingestions of 10 ml of
      date seed extract. Animals of groups 3 and 4 were made diabetic by streptozotocin
      injection, and were given daily subcutaneous injections of 3 IU/day of insulin
      for 8 weeks. Group 4 received, in addition, daily ingestions of 10 ml of seed
      extract. Group 5 were made diabetic with streptozotocin and then given the seed
      extract only. At the end of experiment, rats were decapitated, and the sera were
      separated for estimation of alanine aminotransferase (ALT), aspartate
      aminotransferase, gamma glutamyl transferase, blood urea nitrogen, and serum
      creatinine levels. Livers and kidneys were processed for light microscopic study.
      RESULTS: The mean values of all tested serum levels were significantly higher in
      Group 3 compared to Groups 1, 2 and 4 (with the exception of ALT in the case of
      Group 4). There was no significant change when comparing the mean values of
      Groups 1, 2, and 4. Livers and kidneys of rats in Groups 1, 2, and 4 showed
      normal histology, while those of Group 3 showed histopathological changes.
      CONCLUSION: Date seed extract administration is safe on the liver and kidney. In
      addition, insulin-date seed extract combination minimizes the toxic effects of
      diabetes on these organs.

PMID- 21858388
TI  - Effects of Origanum majorana L. on cadmium induced hepatotoxicity and
      nephrotoxicity in albino rats.
AB  - OBJECTIVE: To evaluate the effect of Origanum majorana L. (OM) against cadmium
      (Cd)-induced hepatotoxicity and nephrotoxicity. METHODS: This study was performed
      at King Khalid University, Abha, Kingdom of Saudi Arabia from September to
      December 2010. Thirty-six male albino rats were divided into 6 groups: control,
      Cd, OM, OM+Cd, OM pre-treated (received OM extract for 14 days followed by Cd for
      14 days), OM post-treated (received Cd for 14 days followed by OM extract for 14
      days). All treatments were orally administered once a day (Cd: 5 mg/kg by weight
      [b.w] and OM: 1 g/kg b.w) for 28 days. Changes in liver biochemical markers
      namely, alanine transaminase, aspartate aminotransferase, alkaline phosphatase
      (ALP) and gamma-glutamyltransferase (GGT), and levels of total protein, urea, and
      creatinine in the serum were determined. Levels of liver and kidney antioxidants
      namely, glutathione, superoxide dismutase and catalase, and lipid peroxidation
      (LPO) were estimated. Differential display using 3 primers: chi 25, 5.8S and NS3
      was performed for liver homogenates. RESULTS: Exposure to Cd increased the levels
      of liver biochemical markers, urea, and creatinine, and lowered total protein
      levels. Exposure to Cd lowered activities of liver and kidney antioxidants, while
      it increased LPO levels. Levels of all disrupted parameters were alleviated by co
      administration and post-administration of OM extract. The NS3 primer was able to
      show genetic variability in livers of all experimental groups. CONCLUSION: The OM
      showed apparent protective and curative effect on Cd-induced hepatotoxicity and
      nephrotoxicity.

PMID- 21858389
TI  - In-hospital adverse clinical outcomes of ST elevation myocardial infarction
      patients with renal dysfunction. Insights from the Saudi Project for Assessment
      of Coronary Events.
AB  - OBJECTIVE: To explore the prognostic value of baseline estimated glomerular
      filtration rate (eGFR) in Saudi patients presenting with ST elevation myocardial
      infarction (STEMI), and its impact on hospital therapies. METHODS: The STEMI
      patients with a baseline serum Creatinine enrolled in the SPACE (Saudi Project
      for Assessment of Coronary Events) registry were analyzed. This study was
      performed in several regions in Saudi Arabia between December 2005 to December
      2007. Based on eGFR levels, patients were classified into: more than 90.1 ml/min
      (normal renal function), 90-60.1 (borderline/mildly impaired renal function), 60
      30 (moderate renal dysfunction), and less than 30 ml/min/1.73 m2 (severe renal
      dysfunction). RESULTS: Two thousand and fifty-eight patients qualified for this
      study. Of these, 1058 patients had renal dysfunction. Patients with renal
      dysfunction were older, and had a higher prevalence of risk factors for
      atherosclerosis. Patients with moderate or severe renal dysfunction were less
      likely to be treated with beta blockers, angiotensin converting enzymes
      inhibitors, statins, or reperfusion therapies. Significantly worse outcomes were
      seen with lower eGFR in a stepwise fashion. The adjusted odds ratio of in
      hospital death in patients with eGFR less than 30 ml/min was 5.3 (95% CI, 1.15
      25.51, p=0.0383). CONCLUSION: A low baseline eGFR in STEMI patients is an
      independent predictor of all major adverse cardiovascular outcomes, and a marker
      for less aggressive in-hospital therapy.

PMID- 21858390
TI  - Effects of intra-abdominal pressure increase on intestinal ischemia and bacterial
      translocation in experimental sepsis model.
AB  - OBJECTIVE: To investigate the safety of laparoscopic intervention for diagnosis
      and treatment at 8 mm Hg pressure in one-hour period on acute peritonitis related
      intra-abdominal sepsis model. METHODS: In this study, we included 32 female
      Wistar-Albino rats, weighing 250 +/- 20 g, and divided them into 4 groups. This
      study was conducted in Istanbul University Experimental Medical Research
      Institution (DETAE) laboratory from April to May 2009. Intra-abdominal sepsis was
      created with intraperitoneal (i.p.) one mL (109 CFU/mL) Escherichia coli (E.
      coli) injection, and pneumoperitoneum was formed with CO2 insufflation at 8 mm Hg
      pressure for one hour i.p. The rats were administered with: Group 1 - one mL i.p.
      isotonic saline; Group 2 - one mL i.p. isotonic saline + pneumoperitoneum; Group
      3 - i.p E. coli; and Group 4 - i.p. E.coli + pneumoperitoneum. Data were analyzed
      using the Statistical Package for Social Sciences version 15 for Windows (SPSS
      Inc, Chicago, IL, USA). RESULTS: Fever and leukocyte values were considered high
      in Groups 3 and 4 compared with Groups 1 and 2 (p=0.001). The administered
      reproduction ratio of the E. coli strain was determined as 0% in Groups 1 and 2,
      and 100% in Groups 3 and 4. CONCLUSION: In this study, as pneumoperitoneum was
      formed for one hour at 8 mm Hg pressure, in case of intra-abdominal derived
      sepsis where emergency intervention is needed, we consider that laparoscopic
      approaches with low pressure may be used safely for diagnosis and treatment.

PMID- 21858391
TI  - Changes in auditory memory performance following the use of frequency-modulated
      system in children with suspected auditory processing disorders.
AB  - OBJECTIVE: To examine the changes in the short-term auditory memory following the
      use of frequency-modulated (FM) system in children with suspected auditory
      processing disorders (APDs), and also to compare the advantages of bilateral over
      unilateral FM fitting. METHODS: This longitudinal study involved 53 children from
      Sekolah Kebangsaan Jalan Kuantan 2, Kuala Lumpur, Malaysia who fulfilled the
      inclusion criteria. The study was conducted from September 2007 to October 2008
      in the Department of Audiology and Speech Sciences, Faculty of Health Sciences,
      Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. The children's age was
      between 7-10 years old, and they were assigned into 3 groups: 15 in the control
      group (not fitted with FM); 19 in the unilateral; and 19 in the bilateral FM
      fitting group. Subjects wore the FM system during school time for 12 weeks. Their
      working memory (WM), best learning (BL), and retention of information (ROI) were
      measured using the Rey Auditory Verbal Learning Test at pre-fitting, post (after
      12 weeks of FM usage), and at long term (one year after the usage of FM system
      ended). RESULTS: There were significant differences in the mean WM (p=0.001), BL
      (p=0.019), and ROI (p=0.005) scores at the different measurement times, in which
      the mean scores at long-term were consistently higher than at pre-fitting,
      despite similar performances at the baseline (p>0.05). There was no significant
      difference in performance between unilateral- and bilateral-fitting groups.
      CONCLUSION: The use of FM might give a long-term effect on improving selected
      short-term auditory memories of some children with suspected APDs. One may not
      need to use 2 FM receivers to receive advantages on auditory memory performance.

PMID- 21858392
TI  - Skin color. Could it be a new fingerprint?
AB  - OBJECTIVE: To prove that the difference in human skin color can be used as a new
      fingerprint. METHODS: A cross-sectional descriptive study was conducted in the
      Faculty of Medicine, The National Ribat University, Khartoum, Sudan between
      January and June 2010. The study consists of 139 subjects, which includes 41
      Sudanese identical twins (82 subjects), 50 subjects from the general population,
      and 7 Chinese. All subjects were free of skin lesions. Based on reflectance
      spectrophotometry, the skin color has been read for all subjects from the inner
      upper arm using the Medisun skin check. Visual judgment on color differences was
      carried out directly with 3 normal observers, and through digital photos.
      RESULTS: Skin color was found to be different in all subjects under the study
      depending on visual judgment, digital photos, and skin color readings.
      Differences in skin color were also found between different parts of the body
      (color map). Color intensity reading in the first twin was 4.010 +/- 0.5, and in
      the second twin was 3.89 +/- 0.44 with a significant difference (p=0.001). The
      general population sample showed significant differences in skin color from each
      other, and from the Chinese group (p=0.002). CONCLUSION: In this study, we found
      that skin color between identical twins is different, as well as in the whole
      population, and could be a new personal identification method, which needs
      further international studies.

PMID- 21858393
TI  - Physicians' awareness of bisphosphonates-related osteonecrosis of the jaw.
AB  - OBJECTIVE: To assess the awareness and knowledge of physicians and dentists
      regarding bisphosphonates related osteonecrosis of the jaw (BRONJ). METHODS: A
      cross-sectional descriptive study was carried out in the Department of Dentistry,
      Riyadh Military Hospital, Kingdom of Saudi Arabia from June to September 2010.
      Data were collected through a self-administered questionnaire distributed among a
      sample of physicians and dentists at the hospital. RESULTS: A total of 222 valid
      completed responses were obtained (response rate: 82.2%). Less than one-third of
      the participants (31.5%) were aware of osteonecrosis of the jaw, while slightly
      more than half of them were treating patients with bisphosphonates (BP). None of
      the physicians had a correct response in all 4 knowledge questions. There were
      statistically significant associations between knowledge and qualification
      (p=0.019), years of experience (p=0.002), and specialty (p=0.034). CONCLUSION: We
      found that physicians and dentists have low awareness and deficient knowledge
      regarding BRONJ, although most of them do prescribe BP to their patients.
      Therefore, intervention to raise awareness and knowledge among healthcare
      providers is needed.

PMID- 21858394
TI  - Soft tissue facial profile of adult Saudis. Lateral cephalometric analysis.
AB  - OBJECTIVE: To develop cephalometric measurements of soft tissue facial profile
      for a sample of adult Saudi males and females and compare it with European
      Americans' norms for any significant differences. METHODS: Sixty-one lateral
      cephalometric radiographs (31 males and 30 females; mean age 23 years) were
      selected from the archives of cephalometric radiograph files at College of
      Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia between June
      2009 and June 2010. Thirteen cephalometric parameters were analyzed
      electronically using the Dolphin version 10 software according to Legan and
      Burstone analysis. Descriptive statistics and p-values were calculated for the
      group comparisons using SPSS program. The statistical significance was determined
      at the 0.05 level of confidence. RESULTS: Adult Saudis generally had increased
      facial convexity associated with retruded mandible, more obtuse lower face-throat
      angle, increased bimaxillary lip protrusion, greater mentolabial sulcus,
      decreased vertical lip-chin ratio, and increased maxillary incisor exposure than
      European-Americans. Saudi females had more obtuse nasolabial angle and decreased
      lower vertical height-depth ratio than European-American females. Comparisons
      between the males and females indicated that Saudi females had a reduced lower
      vertical height-depth ratio, smaller lower lip distance more obtuse nasolabial
      angle and decreased interlabial gap than males. CONCLUSION: The significant
      differences in facial structures of Saudis, European-Americans and between the
      genders should be of a great help for diagnosis of orthodontic and orthognathic
      surgical cases in Saudi adults.

PMID- 21858395
TI  - Smoking habits among medical students in Western Saudi Arabia.
AB  - OBJECTIVE: To estimate the prevalence of tobacco smoking, and understand the
      attitude, practice, and knowledge among medical students. METHODS: A cross
      sectional study was conducted from September 2009 to May 2010. An anonymous, self
      administered, Global Adult Tobacco Survey based questionnaire was completed by
      the students attending the main Medical College of King Abdulaziz University,
      Jeddah, Kingdom of Saudi Arabia. RESULTS: Of the 643 students in the study, 90
      students (14%) indicated that they smoked tobacco at the time of the study. The
      prevalence of smoking was 24.8% among males, and 9.1% among females. Smoking was
      more common in males (p=0.003), but there were more ex-smokers among females
      (p=0.042). The friends and parents were considered the primary influence for
      initiating smoking habit, followed by the media. Ninety percent thought that
      doctors should set a good example by not smoking. Most of the study population
      indicated that smoking is related to serious illnesses; however, non-smokers were
      better aware of such illnesses than smokers. Although most thought that smoking
      tobacco is harmful, approximately 9.5% believe that smoking a water pipe is not.
      CONCLUSION: Despite the good knowledge on the hazards of tobacco consumption,
      24.8% male, and 9.1% female medical students in Jeddah continue to smoke. The
      policymakers should address the factors contributing to the initiation,
      continuation, and spread of this devastating habit.

PMID- 21858396
TI  - Unusual scalp metastasis from follicular thyroid carcinoma.
AB  - Metastatic tumors presenting as soft tissue lesions are relatively rare, and can
      be the source of diagnostic confusion both clinically and histopathologically. We
      present a case of an 82-year-old woman with complaints of painless swelling in
      the right temporo-occipital junction for 3 months, and with unusual scalp
      metastasis of thyroid follicular carcinoma. Use of histopathological examinations
      are significant for determining the tumor type, and arriving at the exact and
      correct diagnosis.

PMID- 21858397
TI  - Combined amino acid and glucose dialysate in children on automated peritoneal
      dialysis.

PMID- 21858398
TI  - The optimal dose of intrathecal sufentanil to be added to low-dose intrathecal
      ropivacaine during anesthesia for cesarean delivery.

PMID- 21858399
TI  - Vaccination against pandemic influenza A H1N1 among health care workers. Lessons
      for the next pandemic.

PMID- 21858400
TI  - Nonbilious vomiting in a small child.

PMID- 21858401
TI  - Pain management of children and adolescents with sickle cell disease presenting
      to the emergency department.

PMID- 21858402
TI  - Potential adverse reactions to herbal medicines in patients attending a
      nephrology clinic in Abu Dhabi, United Arab Emirates.

PMID- 21858403
TI  - Pregnancy outcomes of mothers aged 17 years or less.

PMID- 21858404
TI  - [Management and microsurgical treatment of infundibular dilatations of the
      posterior communicating artery. Series of nine cases and review of the
      literature].
AB  - INTRODUCTION: The infundibular dilatation (ID) of the posterior communicating
      (PCom) artery is defined as the conic, triangular or infundibular shaped, less
      than 3mm wide, origin of the PCom artery from the internal carotid artery. The
      purpose of this paper is to present the personal experience in the microsurgical
      management of the ID, to review the literature and to propose some algorithms to
      improve its clinical and microsurgical management. MATERIAL AND METHODS: Nine
      cases of ID have been operated on through a pterional approach. In four patients
      with subarachnoid hemorrhage (SAH) the ID was considered as the potential source
      of the bleeding; in four cases the ID was treated after a SAH due to the rupture
      of an aneurysm; finally, an ID was treated in patient with diagnosis of
      pseudoxantoma elasticum. RESULTS: In eight cases the ID was clipped and the Pcom
      artery subsequently occluded and in the remaining case the ID was associated with
      a fetal PComA and the ID was reinforced. There were no complications excepting a
      transitory third cranial nerve paresis. The Glasgow Outcome Scale was 5 in all
      cases at discharge and one year later. CONCLUSIONS: The true significance of the
      ID remains unknown, but in some instances it is necessary to consider its
      management: 1. In patients with ruptured aneurysms submitted to microsurgical
      clipping and with an ipsilateral ID, the lesion must be explored and treated; 2.
      In patients with ruptured aneurysms treated with endovascular procedures or
      harbouring an ID contralateral to a microsurgically treated aneurysm, the
      microsurgical indication will be done after considering all risk factors; 3. In
      patients with SAH and an ID as the only potential source of the bleeding there
      would be an indication for microsurgical exploration; 4. The incidental finding
      of an ID should be indication for observation in absence of major risk factors.

PMID- 21858405
TI  - [Usefulness of IPC continuous monitoring in shunt dysfunction].
AB  - Shunt dysfunction is a common situation in neurosurgery. Often symptoms, physical
      examination and radiology are not enough to set a diagnosis. ICP continuous
      monitoring is a safe and reliable tool that provides valuable information about
      CSF dynamics in these patients. Not only quantitative analysis is needed but also
      a qualitative one that enables pathological waves identification, because high
      amplitude B waves are strongly related to shunt dysfunction. In this paper
      experience about ICP continuous monitoring in patients with shunt dysfunction
      suspect is presented. Quantitative and qualitative data analysis led to a correct
      diagnosis, improving all the patients treated according to this criterion. An
      intraparenchymatous Camino(r) sensor and neuroPICture software (developed by
      first author) for data collection and graphic representation were used.
      Complications related to monitoring were absent and graphics obtained useful for
      qualitative analysis.

PMID- 21858406
TI  - [Intraneural cysts of the peroneal nerve in childhood: report of 2 cases and
      literature review].
AB  - Intraneural cysts are benign lesions filled with mucinous content and located
      inside the epineurum of the peripheral nerves. Peroneal nerve is the most
      affected nerve. The entity is rare and its ethiopathology still remains to be
      definitely elucidated. In 2003 Spinner et al published their articular theory,
      implicated in the formation and frequent recurrence of these lesions after
      surgical treatment. The practical application of this theory, nowadays almost
      universally accepted, generated an important diminution in the recurrence rate
      after surgical evacuation of this lesions, previously very elevated. Most of the
      cases of this entity are described in adults. In the present paper we describe
      two pediatric cases and analyze the clinical aspects of these cysts in pediatric
      and adults patients. Peroneal intraneural cysts are one of the differential
      diagnoses in foot drop, and an adequate treatment concludes in a complete
      remission of the symptoms.

PMID- 21858407
TI  - [Iatrogenic cervical epidural hematoma: case report and review of the
      literature].
AB  - BACKGROUND: Around 600 spinal epidural hematoma cases have been previously
      reported. Incidence of paraplegia after epidural anesthesia varies between 0,0005
      and 0,02%. Several possible etiologies have been described in the literature,
      including surgery, trauma, anticoagulant therapy, arteriovenous malformations,
      pregnancy and lumbar puncture. Spinal and epidural anesthesic procedures
      represent the tenth most common cause. But in combination with anticoagulant
      therapy, the forementioned procedures increase its incidence until reaching the
      fifth most common etiological group. We report the case of an 80 year-old-man
      with a cervical epidural hematoma who had a good outcome with conservative
      management. CASE REPORT: 80 year-old-man that developed intense cervicalgia with
      lower limbs weakness showing complete paraplegia and arreflexia 2 hours after
      analgesic treatment with epidural cervical infiltration for cervicoartrosis.
      Cervical MRI showed epidural cervical hematoma between C4 and T1 levels. The
      patient is transferred to our facilities in order to perform surgery. But after
      showing fast recovery, medical conservative management was elected. After one
      month, the patient's condition has improved showing no neurological deficits and
      complete resorption is seen in MRI. CONCLUSIONS: Nowadays, trend is to perform
      surgery in patients with spinal hematoma and significant neurological
      deterioration during the first hours. However, good neurological outcomes can be
      achieved with conservative management, in well selected patients with non
      progressive, incomplete and partial deficits. Presently, we can not predict which
      is the best treatment for each case.

PMID- 21858408
TI  - [Abducens nerve palsy due to postraumatic retroclival and spinal subdural
      hematoma: case report and literature review].
AB  - INTRODUCTION: Retroclival posttraumatic hematomas are extremely rare and almost
      exclusive to childhood. Only one case of retroclival subdural hematoma has been
      reported in the literature to date. CASE REPORT: An 8-year-old boy suffered a
      severe head injury with cervical hyperextension as the result of a bicycle
      accident. On admission his initial Glasgow Coma Score was 13 and he had diplopia
      due to right palsy of the VI nerve. A retroclival subdural hematoma was observed
      by CT and MRI of the craneovertebral junction. Management was conservative and a
      rigid collar was placed. Palsy of VI nerve recovered spontaneously at 6 days and
      at discharge the patient had only cervical pain. Follow up at 3 months after the
      accident showed clinical and radiological resolution. CONCLUSION: Traumatic
      retroclival hematomas are mainly a pediatric entity due to immaturity of the
      cranio-cervical junction. Treatment consists of placement of a rigid collar
      although clinical progression may require surgical evacuation.

PMID- 21858409
TI  - [Occult anterior sacral meningocele].
AB  - BACKGROUND: The anterior sacral meningocele is a rare form of spinal dysraphism
      located in the presacral extraperitoneal space. It is generally asymptomatic and
      appears as a small pelvic mass. CASE DESCRIPTION: We present a case of a 10 year
      old male that develops a bacteria meningitis because of a pararectal abscess that
      is connected with an anterior sacral meningocele. We successfully treated it
      using a posterior approach. CONCLUSION: The aim of the surgery is to repair the
      dural defect and to obliterate the communication between the thecal sac and the
      herniation defect. The posterior approach is the simplest and most effective
      surgical technique because the lower risk of neurological injury than the
      anterior approach.

PMID- 21858410
TI  - Amberlite IR-120 modified with 8-hydroxyquinoline as efficient adsorbent for
      solid-phase extraction and flame atomic absorption determination of trace amounts
      of some metal ions.
AB  - In this study, a solid-phase extraction method combined with atomic absorption
      spectrometry for extraction, preconcentration, and determination of iron
      (Fe(3+)), copper (Cu(2+)), and lead (Pb(2+)) ions at trace levels in water
      samples has been reported. The influences of effective parameters such as flow
      rate, pH, eluent conditions (type, volume, and concentration), sample volumes,
      and interference of matrix ions on metal ions recoveries were studied. Under
      optimized conditions, the limits of detection were found in the range of 0.7-2.2
      MUg L(-1), while preconcentration factors for Fe(3+), Cu(2+), and Pb(2+) ions
      were found to be 166, 200, and 250, respectively, and loading half time (t (1/2))
      values were less than 2 min for all analyte ions. The proposed procedure was
      applied for the determination of metal ions in different water samples with
      recovery of >94.4% and relative standard deviation less than 4.4% for N = 5.

PMID- 21858412
TI  - In vivo imaging of hematopoietic stem cell development in the zebrafish.
AB  - In vivo imaging is crucial for developmental biology and can further help to
      follow cell development/ differentiation in normal and pathological conditions.
      Recent advances in optical imaging techniques has facilitated tracing of the
      developmental dynamics of a specific organ, tissue, or even a single cell. The
      zebrafish is an excellent model for imaging of hematopoiesis due to its
      transparent embryo at early stage; moreover, different zebrafish hematopoietic
      stem cells (HSCs) transgenic lines have been demonstrated as very useful tools
      for illustrating the details of the HSC developmental process. In this review, we
      summarize recent studies related to the non-invasive in vivo imaging of HSC
      transgenics, to show that zebrafish transgenic lines are powerful tools for
      developmental biology and disease. At the end of the review, the perspective and
      some open questions in this field will be discussed.

PMID- 21858414
TI  - Substance use: impact on adherence and HIV medical treatment.
AB  - Substance use is highly prevalent among people living with HIV/AIDS, is often
      comorbid with other mental health problems, related to poor HIV medical outcomes,
      and, is associated with poor medication and treatment adherence. The current
      review reports on the recent state of the literature in terms of substance use
      and its relation to HIV medication and treatment adherence, and offers
      recommendations for advancing treatment and secondary HIV prevention efforts.
      Identifying substance users within HIV primary care and developing, evaluating,
      and refining integrative substance use-mental health-adherence interventions may
      be clinically important targets for effective disease management and may
      contribute to secondary HIV prevention efforts.

PMID- 21858415
TI  - Comparison of radiochemotherapy alone to surgery plus radio(chemo)therapy for non
      metastatic stage III/IV squamous cell carcinoma of the head and neck: A matched
      pair analysis.
AB  - BACKGROUND AND PURPOSE: The standard treatment for non-metastatic stage III/IV
      squamous cell carcinoma of the head and neck varies worldwide. This study
      compared the outcomes of radiochemotherapy alone to surgery followed by
      radio(chemo)therapy (radiotherapy plus/minus concurrent chemotherapy). PATIENTS
      AND METHODS: Data from 148 patients treated with radiochemotherapy alone were
      matched to 148 patients treated with surgery plus radio(chemo)therapy. Groups
      were matched 1:1 for nine potential prognostic factors including age, gender,
      performance status, tumor site, histologic grade, T category, N category, AJCC
      stage, and hemoglobin level before radiotherapy, and compared for locoregional
      control, metastases-free survival, and overall survival. RESULTS: Locoregional
      control rates at 1, 2, and 3 years were 81%, 73%, and 67% after surgery plus
      radio(chemo)therapy and 81%, 74%, and 65% after radiochemotherapy alone (p =
      0.89). Metastases-free survival rates were 86%, 80%, and 75% after surgery plus
      radio(chemotherapy) versus 87%, 80%, and 72% after radiochemotherapy alone (p =
      0.57). Overall survival rates were 80%, 64%, and 63% after surgery plus
      radio(chemo)therapy versus 83%, 68%, and 60% after radiochemotherapy alone (p =
      0.96). On multivariate analyses, T category (p < 0.001), N category (p = 0.004),
      and hemoglobin level prior to radiotherapy (p < 0.001) were associated with
      locoregional control. Histologic grade (p = 0.045), T category (p < 0.001), N
      category (p = 0.003), and hemoglobin level prior to radiotherapy (p < 0.001) were
      associated with metastases-free survival. Histologic grade (p = 0.030), ECOG
      performance status (p = 0.033), T category (p = 0.007), N category (p = 0.024)
      and hemoglobin level before radiotherapy (p < 0.001) were associated with overall
      survival. CONCLUSION: Outcomes of radiochemotherapy alone appeared similar to
      those of surgery plus radio(chemo)therapy. Randomized trials comparing both
      treatments for different tumor sites are warranted.

PMID- 21858416
TI  - [Hemangiosarcoma after breast-conserving therapy of breast cancer: report of four
      cases with molecular genetic diagnosis and literature review].
AB  - BACKGROUND: Hemangiosarcomas of the breast represent a rare disease of the breast
      mainly occurring as secondary neoplasias with a latency of 5-10 years after
      primary treatment of breast cancer and are associated with an unfavourable
      prognosis. Radiation therapy, which is integrated within the concept of breast
      conserving therapy ranks as the main risk factor. PATIENTS AND METHODS: In this
      report we describe the clinical course of 4 patients including their molecular
      genetic pattern and give a summary of the actual literature. RESULTS:
      Hemangiosarcomas occur as a secondary neoplasm with a latency of 5-10 years after
      primary treatment of breast cancer and have an unfavorable prognosis. A genetic
      predisposition is assumed, but we could not find a significant role of tumor
      suppressor genes BRCA1, BRCA2 or p53 in our patients. CONCLUSION: Due to limited
      data available for these tumors, recommendations for therapy include radical
      tumor resection achieving wide free margins and inconsistent regimens of chemo-
      and/or immunetherapy modalities. In the majority these are based on systemic
      therapy regimens for other cutaneous sarcomas, such as Kaposi's sarcoma. Efforts
      should be taken for a nation-wide systematic registration of all cases of post
      irradiation hemangiosarcomas.

PMID- 21858417
TI  - Prolonged survival when temozolomide is added to accelerated radiotherapy for
      glioblastoma multiforme.
AB  - BACKGROUND: The goal of this study was to evaluate accelerated radiotherapy with
      and without temozolomide (TMZ) for glioblastoma multiforme (GBM). METHODS: This
      retrospective analysis evaluated 86 patients with histologically proven GBM who
      were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose
      of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was
      90. A total of 41 patients received radiotherapy only from 2002-2005 and 45
      patients were treated with TMZ concomitantly and after radiotherapy from 2005
      2007. RESULTS: Median overall survival (OS) was 12.5 months and 2-year OS was
      15.4%. Patient characteristics were well balanced between the two groups except
      for better performance status (p = 0.05) and higher frequency of retreatment for
      the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and
      treatment with TMZ (HR 0.60) were correlated with OS in the multivariate
      analysis: treatment with and without TMZ resulted in median OS of 16 months and
      11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45
      patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant
      TMZ. CONCLUSION: TMZ added to accelerated radiotherapy for GBM resulted in
      prolonged overall survival with low rates of severe hematological toxicity.

PMID- 21858418
TI  - Radiosensitization of head and neck cancer cells by the phytochemical agent
      sulforaphane.
AB  - BACKGROUND AND PURPOSE: Sulforaphane is a naturally occurring compound found in
      broccoli and other cruciferous vegetables. Recently it gained attention because
      of its antiproliferative properties in many cancer cell lines. The aim of this
      study was to investigate whether sulforaphane could act as a radiosensitizer in
      head and neck squamous cell carcinoma cell lines. MATERIALS AND METHODS: Four
      head and neck squamous cell carcinoma cell lines (i.e., (HNSCC) SCC9, SCC25,
      CAL27, and FADU) were treated with sulforaphane and subsequently irradiated. Then
      proliferation and clonogenic assays were performed. Apoptosis was detected by
      flow cytometry. Possible regulation of Akt and Mcl-1 was investigated by western
      blotting. RESULTS: Sulforaphane and radiation in combination leads to stronger
      inhibition of cell proliferation and of clonogenic survival than each treatment
      method alone. Western blot analysis of Akt and Mcl-1 showed no changed
      expression. CONCLUSION: Sulforaphane is a promising agent in the treatment of
      head and neck cancer due to its antiproliferative and radio-sensitizing
      properties. A combination of sulforaphane and radiation decreases clonogenic
      survival. Apoptosis is not regulated through Akt or the Mcl-1 protein.

PMID- 21858419
TI  - Assessing health-related quality-of-life changes in informal caregivers: an
      evaluation in parents of children with major congenital anomalies.
AB  - PURPOSE: Relatively few attempts to measure the effects on the health-related
      quality of life (HRQoL) of informal caregivers within the context of economic
      evaluations have been reported. This paper is an exploratory attempt to find
      suitable methods to assess caregivers' HRQoL, using a population of parents of
      children with major congenital anomalies. METHODS: A total of 306 parents of
      children born with either congenital anorectal malformations (ARM) or congenital
      diaphragmatic hernia were surveyed. They rated their current HRQoL on the EQ-VAS.
      After that, they rated their HRQoL again on the assumption that someone would
      take over their caregiving activities completely and free of charge. Finally, the
      parents classified their HRQoL on the EQ-5D. The caregivers' scores on the EQ-VAS
      and the EQ-5D were compared with scores elicited in the general population.
      RESULTS: Most parents indicated that their HRQoL would not change if someone else
      took on their caregiving activities. Some methodological issues may have
      influenced this outcome, such as difficulties in self-assessing HRQoL changes due
      to caregiving, process utility, protest answers, and difficulties in
      understanding the hypothetical question. The HRQoL of the parents was relatively
      low compared with population statistics, especially in the parents of children
      with ARM and in mothers. This can be illustrated by the difference between the
      mean EQ-5D score of the mothers aged 25-34 years of the children with ARM and
      that of the general population (0.83 vs. 0.93; P = 0.002). CONCLUSIONS:
      Significant HRQoL differences exist between parents caring for children with
      congenital anomalies and the general population. It would be useful to further
      improve our understanding of the HRQoL impact of informal caregiving, separating
      'caregiving effects' from 'family effects', and distinguishing parent-child
      relationships from other caregiving situations. This study underlines the
      importance of considering caregivers, also in the context of economic
      evaluations. It indicates that general HRQoL measures, as used in patients, may
      be able to detect HRQoL effects in caregivers, which facilitates the
      incorporation in common economic evaluations of HRQoL effects in carers. Analysts
      and policy makers should be aware that if HRQoL improvement is an important aim,
      they should register HRQoL changes not only in patients but also in their
      caregivers.

PMID- 21858420
TI  - Comparison between cardiopulmonary exercise testing parameters and computed
      tomography findings in patients with thoracic sarcoidosis.
AB  - BACKGROUND: Cardiopulmonary exercise testing (CPET) is a safe and clinically
      useful method to assess functional capacity and to follow disease progression and
      the response to treatment in several clinical conditions. AIM: We set out to
      determine the relationship between outcome measures of CPET and high-resolution
      computed tomography (HRCT) findings in thoracic sarcoidosis. METHODS: A cross
      sectional study was carried out in which 42 nonsmoking outpatients (22 females;
      median age = 46.5 years) were evaluated. All the patients underwent pulmonary
      function tests (PFTs) and CPET. By using CPET, the most probable causes of
      exercise limitation were separated into respiratory mechanics (n = 25) and
      cardiovascular (n = 17). By using HRCT, the following patterns were recorded:
      predominant nodules (n = 18), predominant ground-glass opacity (n = 10), and
      predominant traction bronchiectasis and honeycombing (n = 14). RESULTS: Although
      significant differences have been shown for both PFT parameters and CPET results,
      only the latter were able to distinguish between patients with ground-glass
      opacity and patients with traction bronchiectasis and honeycombing on HRCT. A
      statistically significant difference was found for peak VO(2), breathing reserve,
      and P(A-a)O(2) when patients with predominant traction bronchiectasis and
      honeycombing were compared to patients with other HRCT patterns (p < 0.0001).
      There was no statistical difference among the patterns with abnormal CPET and the
      patterns of abnormalities on HRCT (p > 0.05). CONCLUSION: The functional capacity
      assessed by CPET was strongly influenced by HRCT patterns in sarcoidosis.
      Patients with traction bronchiectasis and honeycombing have lower exercise
      capacity measured by CPET.

PMID- 21858422
TI  - The mind as skills and dispositions: on normativity and mediation.
AB  - On the occasion of the critique of Alfredo Gaete and Carlos Cornejo, this article
      explains and extends the hybrid theory of the mind that I recently presented in
      this journal. Taking inspiration from Rom Harre's program for a hybrid
      psychology, the theory is supposed to be integrative and aims to broaden Harre's
      hybrid psychology by including not just the brain, but also the body, social
      practices, and technological artifacts as mediators of the mind. The mind is
      understood not as a substance of any kind, but as a set of skills and
      dispositions to act, think, and feel. This implies a normative view of the mind,
      according to which psychological phenomena do not simply happen, but are done,
      and can consequently be done more or less well. I provide arguments in favor of
      grounding psychology in normativity rather than conscious experience, and I
      explain why the emphasis on mediators does not represent a threat to the
      ontological primacy of the person in psychology.

PMID- 21858421
TI  - Autologous pluripotent stem cells generated from adult mouse testicular biopsy.

PMID- 21858423
TI  - Purification and characterization of albumin from frog skin of Duttaphrynus
      melanostictus.
AB  - Following determination of trypsin inhibitory activity, a serine protease
      inhibitor was purified and characterized from frog Duttaphrynus melanostictus
      serum. It was identified as serum albumin, with molecular weight of 67 kDa (DmA
      serum). Different from bovine serum albumin, DmA-serum potently inhibited trypsin
      with similar K(i) values around 1.6 * 10-7 M. No inhibitory effect on thrombin,
      chymotrypsin, elastase and subtilisin was observed under the assay conditions.
      The N-terminal amino acid is EAEPHSRI. Subsequently, a protein with same N
      terminal amino acid was purified from skin, termed as DmA-skin. However, DmA-skin
      is distinct from DmA-serum by binding of a haem b (0.5 mol/mol protein), and with
      low trypsin inhibitory activity. Frog albumin is distributed in frog skin and
      exhibited trypsin inhibitory activity, suggesting that it plays important roles
      in skin physiological functions, like water economy, metabolite exchange and
      osmoregulation, etc.

PMID- 21858424
TI  - Functional outcome after surgical treatment of orbital floor fractures.
AB  - In the present article, the authors want to present the results of a
      retrospectively evaluated consecutive series of patients with surgically treated
      isolated orbital floor fractures (OFF; "blow-out fractures") concerning the
      functional outcome after OFF and give detailed recommendations based on the
      clinical and radiological findings. A series of 60 patients with isolated OFF
      over a 5-year period needing surgically repair at the same institution were
      evaluated. Patient data were analysed in terms of preoperative and postoperative
      clinical parameters and radiological findings. The analysed parameters were type
      of fracture, diplopia, gaze restriction, enophthalmos, materials used for repair,
      surgical approach and timing of the surgical intervention. Burst type fractures
      were more often found than punched-out fractures. The most frequently used
      surgical approach was a preseptal transconjunctival approach. An overall decrease
      of gaze restriction (93%), diplopia (89%) and enophthalmos (86%) was observed.
      According to the fracture size, we used Ethisorb patches in smaller fractures and
      resorbable or titanium meshes or autologous bone in larger fractures in most
      cases. Patients who underwent surgery more than 7 days after the trauma showed
      better results with regard to an improvement of diplopia and motility
      disturbances than patients who were treated immediately. In indicated cases, the
      surgical repair of OFF leads to very good results if the anatomical and
      functional properties of the orbit and its contents are respected. The applied
      strategy and means presented in our study proved of value and can therefore be
      recommended.

PMID- 21858425
TI  - Residual hearing preservation using the suprameatal approach for cochlear
      implantation.
AB  - OBJECTIVE: Cochlear implantation of patients with high-frequency hearing loss and
      residual low-frequency hearing has become a new treatment standard within the
      last years. The objective of this study was to evaluate the rate of hearing
      preservation in cochlear implantation for electric-acoustic stimulation using the
      suprameatal approach. METHODS: Five patients (mean age 48.2 years) who were
      supplied with Med El (Combi 40+, Pulsar) cochlear implants and various different
      electrodes (Custom made, Flex soft, Flex EAS) were evaluated for residual hearing
      preservation after a mean follow-up time of 35.6 months (range 24 to 77 months).
      RESULTS: Three patients showed partial hearing preservation, whereas 2 patients
      experienced a complete loss of residual hearing. CONCLUSION: Although hearing
      preservation rates in this series of patients operated on using the suprameatal
      approach were inferior as compared with a series using the standard mastoidectomy
      approach, this study shows that it is in fact possible to preserve residual
      hearing using a non-mastoidectomy surgical technique for cochlear implantation.
      Nevertheless, more experience is necessary to answer the question whether this
      technique can be thoroughly recommended in cochlear implantation for electric
      acoustic stimulation.

PMID- 21858426
TI  - [Prophylaxis and therapy of the glucocorticoid-induced osteoporosis - a review of
      recent guidelines].
AB  - Several international guidelines for treatment and prophylaxis of glucocorticoid
      induced osteoporosis (GIO) have been published. Consistent with the development
      of new therapeutic agents, a different approach to treatment can be recognized
      depending on the year of publication. Also, new insights for the postmenopausal
      osteoporosis leave their marks on recent guidelines. The working committee on
      Osteology of the Austrian Society for Rheumatology and Rehabilitation (OGR)
      sifted through actual guidelines and recent literature on the topic to develop
      recommendations for the prophylaxis and treatment of the GIO.

PMID- 21858427
TI  - Effect of diet orange soda on urinary lithogenicity.
AB  - Studies have shown that certain beverages decrease urinary lithogenicity by
      increasing urine citrate excretion. Diet Sunkist Orange soda had the highest
      concentration of citrate and total alkali content among 12 diet sodas previously
      assayed. We studied the effect of Diet Sunkist Orange soda consumption on urinary
      chemistry. Nine healthy men and women ages 26-54 years completed the study.
      During the control period, subjects drank 36 oz of water for 3 days in addition
      to their own, self-selected diet and recorded a food diary. During the study
      period, the subjects drank three 12-oz cans of Diet Sunkist Orange soda a day
      instead of water, and replicated their diets from the control period. In each
      period, the subjects performed 24-h urine collections on days 2 and 3. Urine
      chemical analysis was performed, including urinary citrate levels and pH. Diet
      Sunkist Orange soda increased urinary citrate excretion by 60 mg/day, which was
      not statistically significant (95% CI -75 to 195, P value 0.34). There was no
      significant change in pH from the control period to the study period (pH: 6.29
      6.21; 95% CI: -0.09 to 0.25, P = 0.30). Urine volumes and creatinine excretions
      were not significantly different between the control and study periods. Despite
      the relatively high citrate and total alkali content of Diet Sunkist Orange soda,
      the volume consumed in this study (36 oz per day) did not provide sufficient
      potential base to significantly alter urine composition in healthy subjects with
      normocitraturia. The effect of Diet Sunkist Orange soda on urinary chemistry in
      patients with hypocitraturia and nephrolithiasis is not likely to have a
      clinically significant effect to prevent calcium or uric acid stones.

PMID- 21858428
TI  - The impact of metaphylaxis of kidney stone disease in the renal function at long
      term in active kidney stone formers patients.
AB  - A total of 150 patients were included in the analysis. Through chart review, we
      estimated glomerular filtration rate in the first visit and, at least, 5 years
      later. All patients were divided into two groups: (1) metaphylaxis adherents (n =
      74) and (2) metaphylaxis non-adherents (n = 76). We followed all patients for at
      least 5 years. The Scr percentage of patients and GFR <60 mL/min was compared
      between groups. Variables were compared between groups using t test, chi(2)
      tests, odds ratios with 95% confidence intervals. There were no differences at
      baseline between groups. After 5 years of follow-up, GFR was 77.9 mL/min in non
      adherent-metaphylaxis group and in the adherent-metaphylaxis group was 87.3
      mL/min, with p value of 0.02. After 5 years of follow-up, we had a GFR <60 mL/min
      in the adherent-metaphylaxis group (4.89 vs. 21.95%) with p value of 0.001 and OR
      = 5.36; IC-95% = 1.95-14.8. Metaphylaxis of kidney stone disease could prevent
      chronic kidney disease.

PMID- 21858429
TI  - Antimicrobial factor from Bacillus amyloliquefaciens inhibits Paenibacillus
      larvae, the causative agent of American foulbrood.
AB  - Bacillus amyloliquefaciens LBM 5006 produces an antimicrobial factor active
      against Paenibacillus larvae, a major honeybee pathogen. The antagonistic effect
      and the mode of action of the antimicrobial factor were investigated. The
      antibacterial activity was produced starting at mid-logarithmic growth phase,
      reaching its maximum during the stationary phase. Exposure of cell suspensions of
      P. larvae to this antimicrobial resulted in loss of cell viability and reduction
      in optical density associated with cell lysis. Scanning electron microscopy
      showed damaged cell envelope and loss of protoplasmic material. The antimicrobial
      factor was stable for up to 80 degrees C, but it was sensitive to proteinase K
      and trypsin. Mass spectrometry analysis indicates that the antimicrobial activity
      is associated with iturin-like peptides. The antimicrobial factor from B.
      amyloliquefaciens LBM 5006 showed a bactericidal effect against P. larvae cells
      and spores. This is the first report on iturin activity against P. larvae. This
      antimicrobial presents potential for use in the control of American foulbrood
      disease.

PMID- 21858430
TI  - Kynurenines in Parkinson's disease: therapeutic perspectives.
AB  - Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder the
      pathomechanism of which is not yet fully known. With regard to the molecular
      mechanism of development of the disease, oxidative stress/mitochondrial
      impairment, glutamate excitotoxicity and neuroinflammation are certainly
      involved. Alterations in the kynurenine pathway, the main pathway of the
      tryptophan metabolism, can contribute to the complex pathomechanism. There are
      several possibilities for therapeutic intervention involving targeting of this
      altered metabolic route. The development of synthetic molecules that would shift
      the altered balance towards the achievement of neuroprotective effects would be
      of great promise for future clinical studies on PD.

PMID- 21858431
TI  - Differences between dextroamphetamine and methamphetamine: behavioral changes and
      oxidative damage in brain of Wistar rats.
AB  - In this study methamphetamine (m-AMPH) and dextroamphetamine (d-AMPH) were
      compared to determine the potency of the two drugs on behavior and oxidative
      damage in brain of rats. Male adult Wistar rats were given single (acute
      administration) or repeated (chronic administration, 14 days) intraperitoneal
      injections of saline (0.9% NaCl), d-AMPH (2 mg/kg) or m-AMPH (0.25, 0.5, 1 or 2
      mg/kg). Locomotor activity was evaluated in open-field apparatus 2 h after the
      last drug injection. Additionally, thiobarbituric acid reactive substances
      (TBARS) and protein carbonyl formation were measured in the prefrontal cortex,
      amygdala, hippocampus and striatum. In both experiments, d-AMPH and m-AMPH (all
      doses administered) increased the locomotor activity of animals, meantime, no
      significant difference between d-AMPH and m-AMPH was observed. d-AMPH and m-AMPH
      increased lipid and protein damage, but m-AMPH was more potent than d-AMPH,
      however, this effect varies depending on the brain region and the experimental
      protocol. The results of this study show that d-AMPH and m-AMPH have similar
      behavioral effects, which previous studies had already reported. On the other
      hand, this study demonstrated that the m-AMPH induces oxidative damage greater
      than d-AMPH, showing neurochemical differences previously unknown.

PMID- 21858432
TI  - Systematic review of safety in paediatric drug trials published in 2007.
AB  - BACKGROUND: There is now greater involvement of children in drug trials to ensure
      that paediatric medicines are supported by sound scientific evidence. The safety
      of the participating children is of paramount importance. Previous research shows
      that these children can suffer moderate and severe adverse drug reactions (ADRs)
      in clinical trials, yet very few of the trials designated a data safety
      monitoring board (DSMB) to oversee the trial. METHODS: Safety data from a
      systematic review of paediatric drug randomised controlled trials (RCTs)
      published in 2007 were analysed. All reported adverse events (AEs) were
      classified and assessed to determine whether an ADR had been experienced. ADRs
      were then categorised according to severity. Each trial report was examined as to
      whether an independent DSMB was in place. RESULTS: Of the 582 paediatric drug
      RCTs analysed, 210 (36%) reported that a serious AE had occurred, and in 15%
      mortality was reported. ADRs were detected in more than half of the RCTs (305);
      66 (11%) were severe, and 79 (14%) were moderate. Severe ADRs involved a wide
      range of organ systems and were frequently associated with cytotoxic drugs,
      antiparasitics, anticonvulsants and psychotropic drugs. Two RCTs reported
      significantly higher mortality rates in the treatment group. Only 69 (12%) of the
      RCTs stated there was a DSMB. DSMBs terminated five RCTs and changed the protocol
      in one. CONCLUSIONS: Children participating in drug RCTs experience a significant
      amount and a wide range of ADRs. DSMBs are needed to ensure the safety of
      paediatric participants in clinical drug trials.

PMID- 21858433
TI  - Aliphatic hydrocarbons, polycyclic aromatic hydrocarbons, polychlorinated
      biphenyls, organochlorine, and organophosphorous pesticides in surface sediments
      from the Arc river and the Berre lagoon, France.
AB  - INTRODUCTION: The Arc River and Berre lagoon are one of important river basin
      hydrosystem in the South of France that receives industrial and municipal
      wastewaters from the adjacent area. MATERIALS AND METHODS: Due to its social and
      economic impact as well as ecological function of basin, an assessment of
      environmental risk due to mobilization of contaminants is necessary. Thus, the
      study aims to determine the spatial distribution of n-alkanes, polycyclic
      aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine
      and organophosphorous pesticides in surface sediments and their potential origins
      by using gas chromatography coupled to mass spectrometry. RESULTS AND DISCUSSION:
      Total alkanes concentrations ranged from 563 to 5,068 MUg kg(-1) sediment dry
      weight (dw), the sum of 17 PAHs ranged from 153 to 1,311 MUg kg(-1) dw, the sum
      of seven PCBs concentrations ranged from 0.3 to 466.8 MUg kg(-1) dw, and the
      total pesticides concentrations ranged from 0.02 to 7.15 MUg kg(-1) dw. Ratios of
      specific n-alcanes (carbon preference index, natural n-alkanes ratio, and
      terrigenous/aquatic ratio) and ratios of selected PAH (anthracene (Ant)/(Ant +
      Phe), fluoranthene (Fl)/(Fl + pyrene (Pyr)), BaA/(BaA + chrysene (Chry)),
      indeno[1,2,3,c,d]pyrene (IPyr)/(IPyr + BghiP)) were calculated to evaluate the
      possible sources of hydrocarbons. CONCLUSIONS: The evaluations suggest the
      sources of hydrocarbons in the sediments were generally biogenic and markedly
      more pyrolytic rather than petrogenic. In the perspectives of environmental risk
      assessment, all contaminants levels were also compared with sediments quality
      guidelines (SQG) resulting that the contamination levels in all stations were
      most of the time lower than their respective SQG. While, for PCBs concentrations,
      three stations (A8, B1, and B2) were higher than their effect range median values
      which may indicate high potential toxicity of the sediment with probable adverse
      effects to the living biota.

PMID- 21858434
TI  - Modelling of spatial contaminant probabilities of occurrence of chlorinated
      hydrocarbons in an urban aquifer.
AB  - In this study, a 3D urban groundwater model is presented which serves for
      calculation of multispecies contaminant transport in the subsurface on the
      regional scale. The total model consists of two submodels, the groundwater flow
      and reactive transport model, and is validated against field data. The model
      equations are solved applying finite element method. A sensitivity analysis is
      carried out to perform parameter identification of flow, transport and reaction
      processes. Coming from the latter, stochastic variation of flow, transport, and
      reaction input parameters and Monte Carlo simulation are used in calculating
      probabilities of pollutant occurrence in the domain. These probabilities could be
      part of determining future spots of contamination and their measure of damages.
      Application and validation is exemplarily shown for a contaminated site in
      Braunschweig (Germany), where a vast plume of chlorinated ethenes pollutes the
      groundwater. With respect to field application, the methods used for modelling
      reveal feasible and helpful tools to assess natural attenuation (MNA) and the
      risk that might be reduced by remediation actions.

PMID- 21858435
TI  - Recurrence of inguinal herniae following removal of infected prosthetic meshes: a
      review of the literature.
AB  - PURPOSE: Late-onset mesh infection, occurring months to years following hernia
      repair, is a rare complication of hernia surgery. Its management usually requires
      removal of the mesh. The aim of this paper was to assess the rate of recurrence
      of inguinal herniae following removal of the mesh for late onset deep mesh
      infection. METHODS: We performed a literature review to assess the rate of
      recurrence of herniae following the removal of a delayed onset infected mesh.
      Relevant studies from January 1966 to June 2010 were identified from a Medline,
      Pub Med, Embase, Scopus and Cochrane database search. Studies that reported
      recurrence of the hernia following removal of delayed onset infected meshes were
      included. Results were tabulated and analysed to derive conclusions. RESULTS:
      Some 153 abstracts were reviewed and 12 potential studies initially identified;
      of these, only 7 were finally included in this review. The included studies were
      six case series and one case report and comprised a total of 40 patients in whom
      delayed-onset infected mesh was removed. The median follow-up period after the
      removal of the infected mesh was 26 months. Of these 40 patients, only 2 (<5%)
      developed a recurrent hernia. Removal of the mesh resulted in resolution of
      symptoms in the majority of the patients. CONCLUSION: Based on this review,
      removal of a late-onset infected mesh results in resolution of symptoms in the
      majority of cases, whereas recurrence of hernia is not common. However, further
      research is required as the number of patients in our review is relatively small.

PMID- 21858436
TI  - Femoral hernia containing incarcerated fallopian tube.

PMID- 21858437
TI  - New directions in clinical outcomes assessment : VIth International Symposium on
      Interventional Electrophysiology in the Management of Cardiac Arrhythmias.
AB  - In recent years, electrophysiology clinical research has made tremendous
      progress. Not only have the standards for conducting research and assessing
      clinical outcomes improved substantially, but the power of well-conducted and
      designed randomized clinical trials has been realized. This has led to the
      emergence of a plethora of randomized clinical trials in electrophysiology.
      Despite these improvements, there is an immense need to explore and develop
      better approaches for assessing clinical outcomes. In this article, I review the
      strengths, challenges, and limitations of randomized clinical trials, especially
      as they relate to the field of electrophysiology. To address some of these
      challenges, I propose potential solutions that involve enhancing clinical trials
      and complementing them with large registries and databases of electronic medical
      records. If prudently developed and executed, these new directions in assessing
      clinical outcomes have great potential to inform, and thereby improve the care of
      patients receiving electrophysiologic interventions.

PMID- 21858438
TI  - Zygospore formation between homothallic and heterothallic strains of Closterium.
AB  - Zygospore formation in different strains of the Closterium peracerosum-strigosum
      littorale complex was examined in this unicellular isogamous charophycean alga to
      shed light on gametic mating strains in this taxon, which is believed to share a
      close phylogenetic relationship with land plants. Zygospores typically form as a
      result of conjugation between mating-type plus (mt(+)) and mating-type minus (mt(
      )) cells during sexual reproduction in the heterothallic strain, similar to
      Chlamydomonas. However, within clonal cells, zygospores are formed within
      homothallic strains, and the majority of these zygospores originate as a result
      of conjugation of two recently divided sister gametangial cells derived from one
      vegetative cell. In this study, we analyzed conjugation of homothallic cells in
      the presence of phylogenetically closely related heterothallic cells to
      characterize the reproductive function of homothallic sister gametangial cells.
      The relative ratio of non-sister zygospores to sister zygospores increased in the
      presence of heterothallic mt(+) cells, compared with that in the homothallic
      strain alone and in a coculture with mt(-) cells. Heterothallic cells were
      surface labeled with calcofluor white, permitting fusions with homothallic cells
      to be identified and confirming the formation of hybrid zygospores between the
      homothallic cells and heterothallic mt(+) cells. These results show that at least
      some of the homothallic gametangial cells possess heterothallic mt(-)-like
      characters. This finding supports speculation that division of one vegetative
      cell into two sister gametangial cells is a segregative process capable of
      producing complementary mating types.

PMID- 21858439
TI  - Prediction of benignity of solid adnexal masses.
AB  - OBJECTIVE: The aim of this study was to identify the sonographic features of
      solid ovarian masses and to determine whether they may be managed conservatively.
      STUDY DESIGN: Sixty-three patients from September 1999 to September 2008 with
      solid adnexal masses demonstrating acoustic attenuation, absent Doppler
      vascularity and minimal or no cystic component were retrospectively reviewed. 20
      patients without pathologic results or follow-up studies were excluded. The
      remaining 43 patients had follow-up imaging studies and/or surgical treatment.
      The median age of the study group was 52 years (range 16-80 years). RESULTS:
      Twenty-nine patients with solid adnexal masses were managed non-surgically. Their
      age range was 26-80 years (median 56). The size of the masses ranged from 0.7 to
      8.3 cm (median 2.2). The follow-up time ranged from 3 to 76 months (median 30).
      19 masses (65.5%) showed no change on the follow-up exam. Two masses showed an
      increase in size (6.9%), and eight masses (27.6%) showed a decrease in size or
      complete resolution. All these masses had well-circumscribed margins, were
      homogeneous, with increased attenuation, and had minimal or no vascular flow or
      cystic component. Normal ovarian tissue was detected in the margins of 24 of the
      masses (85.7%). These patients exhibited no subsequent evidence of malignancy,
      such as development of metastases, local invasion, or ascites. 14 patients with
      solid adnexal masses underwent surgical treatment. Their age range was 16-72
      years (median 40). The size of the excised masses ranged from 1.8 to 12.3 cm
      (median 3.2 cm). Normal ovarian tissue was sonographically demonstrated in ten of
      these masses (71.4%). All 14 patients (100%) had benign results at pathology.
      Four patients showed no ovarian neoplasm. Ten patients had benign ovarian
      neoplasms, including four fibromas, three fibrothecomas, one Brenner tumor, one
      granulosa cell tumor, and one mature teratoma. CONCLUSION: We present a
      retrospective study of both surgical and nonsurgical management of solid ovarian
      masses. None of the sonographically diagnosed benign-appearing solid adnexal
      masses were subsequently proved to be malignant either at pathology or by
      clinical course, suggesting that ultrasound can accurately predict benignity in
      these masses and that conservative management is an option in these patients.

PMID- 21858440
TI  - Cancer in pregnancy. Part II: treatment options of breast and other non
      gynecological malignancies.
AB  - PURPOSE: In case of non-gynecological solid tumors and hematological malignancies
      diagnosed during pregnancy, individual diagnostic and treatment options must be
      established by an interdisciplinary team. METHODS: In part II of the present
      review we report on diagnostic and therapeutic principles in distinct entities of
      solid and hematological malignancies. RESULTS: On the basis of a review of the
      current literature, clinical guidelines and algorithms have been established for
      diagnosis and therapy of maternal cancer during pregnancy. CONCLUSIONS: The
      prognosis of the malignancy and the patient's informed consent must be taken into
      consideration when the well-being of the expectant mother is weighed against the
      well-being of the unborn child in case of maternal cancer during pregnancy.

PMID- 21858441
TI  - Cancer in pregnancy. Part I: basic diagnostic and therapeutic principles and
      treatment of gynecological malignancies.
AB  - PURPOSE: Cancer in pregnancy is a rare circumstance. However, the coincidence of
      pregnancy and malignancy is supposed to increase due to a general tendency of
      postponing childbearing to older age. To date, clinical guidelines are scarce and
      experience regarding therapeutic management is limited to case reports. METHODS:
      This review focuses on general diagnostic and therapeutic principles including
      systemic therapy for malignancies in pregnancy. RESULTS: In part I, we report on
      diagnosis and therapy of gynecological tumors. CONCLUSION: The diagnosis of
      gestational cancer faces both oncologist and obstetrician to the dilemma of
      applying appropriate diagnostic techniques and adequate local and systemic
      therapy to an expectant mother without harming the fetus.

PMID- 21858442
TI  - Pulmonary alveolar hemorrhage possibly associated with lenalidomide use.

PMID- 21858443
TI  - Acral ischemia as a presenting manifestation of essential thrombocythemia.

PMID- 21858444
TI  - Urachal remnant infection leading to Pseudomonas aeruginosa bacteremia in
      induction therapy for adult B-cell acute lymphoblastic leukemia.

PMID- 21858445
TI  - Skewed T-cell subsets and enhanced macrophages phagocytosis in the spleen of
      patients with immune thrombocytopenia failing glucocorticoids.
AB  - T-cell abnormalities are considered important in the pathogenesis of immune
      thrombocytopenia (ITP). Th1 polarization of the immune response in peripheral
      blood mononuclear cells (PBMC) has been observed in ITP patients. However,
      whether the polarization of T-cell subsets exists in splenocytes remains unclear.
      In the present study, we detected T-cell subsets and macrophage phagocytosis
      capacity in the spleens of ten ITP patients failing first-line treatment.
      Compared with traumatic patients, ITP patients had similar percentages of Th1,
      Tc1, and T1 (Th1 + Tc1) cells, but lower percentages of Th2 and Tc2 cells, which
      did not, however, reach significant difference. ITP patients had significantly
      lower percentages of T2 (Th2 + Tc2) cells than the control group (P = 0.035). The
      ratios of Th1/Th2 and T1/T2 were significantly higher in ITP patients than the
      control group (P = 0.025 and 0.027, respectively). Splenic macrophages from ITP
      patients presented significant increase in phagocytic capacity (P < 0.001). The
      phagocytosis rate in splenic macrophages positively correlated with the ratio of
      Th1/Th2 (r = 0.767, P = 0.010), but negatively correlated with percentage of Th2
      cells (r = -0.804, P = 0.005). The skewed T-cell subsets and enhanced macrophage
      phagocytosis in the spleen may be closely related to the disease onset and status
      of ITP.

PMID- 21858447
TI  - Disappearance of malignant cells by effusion drainage alone in two patients with
      HHV-8-unrelated HIV-negative primary effusion lymphoma-like lymphoma.
AB  - Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma usually
      confined to the body cavities of predominantly immunosuppressed patients infected
      with human herpes virus-8 (HHV-8). In PEL, malignant cells are usually negative
      for B-cell markers, such as CD19, CD20, and CD79a, but are positive for
      activation and plasma cell-related markers, such as CD30, CD38, and CD138. It has
      been reported that HHV-8-unrelated PEL shows high expression of B-cell markers,
      which is referred to as PEL-like lymphoma. Here, we report two cases of HHV-8
      unrelated HIV-negative PEL-like lymphoma in which malignant cells regressed
      spontaneously after effusion drainage alone. These cells expressed B-cell
      markers, such as CD20. No chemotherapy was given to either patient, as they were
      of an advanced age, and both achieved a complete response by effusion drainage
      alone. One showed a complete response for 16 months after effusion drainage, and
      the other has survived for 11 months with a complete response. This suggests that
      sufficient drainage of serous effusion may induce and maintain a complete
      response in some patients with HHV-8-unrelated HIV-negative PEL-like lymphoma,
      which represents an excellent treatment option for elderly patients with this
      disease.

PMID- 21858446
TI  - Age-associated alteration of gammadelta T-cell repertoire and different profiles
      of activation-induced death of Vdelta1 and Vdelta2 T cells.
AB  - It has been suggested that gammadelta T cells are involved in certain autoimmune
      disorders. To establish reference data for clinical studies to explore the role
      of gammadelta T cells in autoimmune bone marrow failure syndrome, we examined the
      gammadelta T-cell repertoire in 120 healthy Japanese individuals by flow
      cytometry. The average numbers of T lymphocytes in blood were as follows: 1,084
      +/- 369 (SD) alphabeta T cells, 68 +/- 44 gammadelta T cells, 16 +/- 12 Vdelta1 T
      cells, and 43 +/- 36 Vdelta2 T cells (/MUl). Absolute numbers of gammadelta T
      cells decreased with aging (R = -0.378, P < 0.001). The decrease of gammadelta T
      cells was the result of reduction of Vdelta2, but not of Vdelta1, T cells.
      Numbers of Vdelta2 T cells were significantly higher in male than in female
      donors (P = 0.007). The Vdelta2 T cells but not Vdelta1 T cells showed a rapid
      reduction in cell numbers on mitogen stimulation, which was accompanied by modest
      down-regulation of Bcl-2 protein expression. These results indicate that age and
      gender have a major impact on gammadelta T-cell repertoire in Japanese donors, as
      well as European and American donors. The age-related decrease of Vdelta2 T cells
      may be explained by their susceptibility to activation-induced cell death.

PMID- 21858448
TI  - Dose- and tissue-specific interaction of monoterpenes with the gibberellin
      mediated release of potato tuber bud dormancy, sprout growth and induction of
      alpha-amylases and beta-amylases.
AB  - Gibberellins (GA) are involved in bud dormancy release in several species. We
      show here that GA-treatment released bud dormancy, initiated bud sprouting and
      promoted sprout growth of excised potato tuber bud discs ('eyes'). Monoterpenes
      from peppermint oil (PMO) and S-(+)-carvone (CAR) interact with the GA-mediated
      bud dormancy release in a hormesis-type response: low monoterpene concentrations
      enhance dormancy release and the initiation of bud sprouting, whereas high
      concentrations inhibit it. PMO and CAR did, however, not affect sprout growth
      rate after its onset. We further show that GA-induced dormancy release is
      associated with tissue-specific regulation of alpha- and beta-amylases. Molecular
      phylogenetic analysis shows that potato alpha-amylases cluster into two distinct
      groups: alpha-AMY1 and alpha-AMY2. GA-treatment induced transcript accumulation
      of members of both alpha-amylase groups, as well as alpha- and beta-amylase
      enzyme activity in sprout and 'sub-eye' tissues. In sprouts, CAR interacts with
      the GA-mediated accumulation of alpha-amylase transcripts in an alpha-AMY2
      specific and dose-dependent manner. Low CAR concentrations enhance the
      accumulation of alpha-AMY2-type alpha-amylase transcripts, but do not affect the
      alpha-AMY1-type transcripts. Low CAR concentrations also enhance the accumulation
      of alpha- and beta-amylase enzyme activity in sprouts, but not in 'sub-eye'
      tissues. In contrast, high CAR concentrations have no appreciable effect in
      sprouts on the enzyme activities and the alpha-amylase transcript abundances of
      either group. The dose-dependent effects on the enzyme activities and the alpha
      AMY2-type alpha-amylase transcripts in sprouts are specific for CAR but not for
      PMO. Different monoterpenes therefore may have specific targets for their
      interaction with hormone signalling pathways.

PMID- 21858449
TI  - Involvement of opioid system in cognitive deficits induced by ?9
      tetrahydrocannabinol in rats.
AB  - RATIONALE: Cannabis is a widely used illicit substance. ?(9)-Tetrahydrocannabinol
      (THC), the major psychoactive component of cannabis, is known to induce cognitive
      deficits that closely resemble the impairment observed in schizophrenic patients.
      We previously reported that THC (6 mg/kg) impairs spatial memory in the eight-arm
      radial maze, and that this memory disturbance was reversed by the cannabinoid
      CB(1) receptor antagonist rimonabant (0.1 mg/kg), suggesting that the effect of
      THC is mediated through cannabinoid CB(1) receptors. OBJECTIVES: The present
      study was designed to examine the possible involvement of opioid receptors in the
      THC-induced impairment of spatial memory. METHODS: The effects of treatment with
      the nonselective opioid receptor antagonist naloxone (0.3 and 1 mg/kg), the MU
      opioid receptor antagonist beta-funaltrexamine (0.3 and 1 mg/kg), the delta
      opioid receptor antagonist naltrindole (1 and 3 mg/kg), and the kappa-opioid
      receptor antagonist nor-binaltorphimine (0.03 and 0.1 mg/kg) on the impairment of
      spatial memory induced by THC were evaluated using the eight-arm radial maze.
      RESULTS: The nonselective opioid receptor antagonist naloxone, the MU-opioid
      receptor antagonist beta-funaltrexamine, and the kappa-opioid receptor antagonist
      nor-binaltorphimine, but not the delta-opioid receptor antagonist naltrindole,
      attenuated THC-induced cognitive deficits, suggesting an involvement of MU- and
      kappa-opioid receptors in this behavioral response. CONCLUSIONS: These results
      demonstrate that the endogenous opioid system is involved in the regulation of
      the acute short-term and working memory deficits induced by cannabis.

PMID- 21858450
TI  - Roles for CCN2 in normal physiological processes.
AB  - CCN2, also known as connective tissue growth factor, is a member of the CCN (CCN1
      6) family of modular matricellular proteins. Analysis of CCN2 function in vivo
      has focused primarily on its key role as a mediator of excess ECM synthesis in
      multiple fibrotic diseases. However, CCN2 and related family members are widely
      expressed during development. Recent studies using new genetic models are
      revealing that CCN2 has essential roles in the development of many tissues. This
      review focuses on current and emerging data on CCN2 and its functions in
      chondrogenesis and angiogenesis, and on new studies showing that CCN2 has
      essential functions during embryonic and postnatal development in a number of
      epithelial tissues.

PMID- 21858452
TI  - Obturator hernia--a condition seldom thought of and hence seldom sought.
AB  - PURPOSE: Obturator hernia is an extremely rare type of hernia with an incidence
      of less than 1% of all abdominal wall hernias occurring predominantly in elderly
      females characterized by protrusion of the intra-abdominal viscera into the
      obturator foramen. It presents with pain along the medial aspect of the thigh
      referred to the knee due to compressed obturator nerve and sometimes as an
      uncommon cause of intestinal obstruction. It remains a clinical diagnostic
      dilemma and often perplexing the decision for surgery. This explanatory review
      emphasizes and illuminates its various facets under the rationale of its
      diagnosis and management to familiarize surgeons with the condition. METHODS: The
      data for the present review was obtained by searching in PubMed and other
      databases using key terms "obturator hernia", "abdominal hernia", "intestinal
      obstruction", and "Howship-Romberg sign". Many original articles, reviews, and
      case reports were selected. RESULTS: Since it is very rare that a mass can be
      found on inspection of the medial aspect of the thigh and the clinical signs are
      not always present, hence obturator hernia is a condition which leads to both
      difficult and delayed clinical diagnosis and consequently having a significant
      morbidity and mortality rates, especially in the elderly. CONCLUSION: Obturator
      hernia should always be in the differential diagnosis in septuagenarian to
      nonagenarian patients with nonspecific signs and symptoms of intestinal
      obstruction. Computed tomography of abdomen and pelvis has been found to be the
      gold standard for preoperative diagnosis and this condition necessitates
      immediate surgical reduction and repair of the defect either by open or
      laparoscopic approach.

PMID- 21858453
TI  - Ex-situ field application of electrokinetics for remediation of shooting-range
      soil.
AB  - Electrokinetic process for remediation of a shooting-range site was evaluated in
      this study. By field operation for 100 days, the newly designed electrokinetic
      system was evaluated for process stability, performance, and efficiency. The
      field site of this study was an abandoned military shooting range located in the
      Civilian Control Line of South Korea. The target area, only, was heavily
      contaminated by Pb and Cu to a depth of 0.5 m. After dry-sieving of the field
      soil to separate particulate Pb, two cells in a hexagonal (two-dimensional)
      arrangement, including ten anodes outside the cell and two cathodes in the
      middle, were prepared. The pH of each electrolyte was adjusted by use of
      concentrated HNO(3), resulting in acid-enhanced electrokinetics. The monitoring
      results indicated that overall removal of heavy metals (Pb, Cu) was achieved, and
      that both heavy metals were removed from outside the cell. The average final
      efficiency of removal of Pb and Cu was 39.5 +/- 35 and 63.8 +/- 12%,
      respectively. Although the feasibility of this system was confirmed, for
      commercialization of the process confirmed drawbacks must be improved by further
      study.

PMID- 21858454
TI  - Assessing geochemical influence of traffic and other vehicle-related activities
      on heavy metal contamination in urban soils of Kerman city, using a GIS-based
      approach.
AB  - Heavy metal pollution caused by traffic activities is increasingly becoming a
      great threat to urban environmental quality and human health. In this paper,
      soils of Kerman urban and suburban areas were collected to assess the potential
      effects of traffic and other vehicle-related pollution by heavy metal
      accumulation in soils. Eighty-six samples were collected along streets and from
      residential and rural sectors, as well as vehicle-related workshops from depth of
      0-5 and 15-20 cm and analyzed by flame atomic absorption spectrometry (FAAS) for
      heavy metals (Cd, Cr, Cu, Pb, Sn and Zn), as well as major elements (Al, Ca, Fe
      and Mn). Several hot-spot areas were identified in the composite geochemical maps
      produced based on Geographical Information System (GIS) technology. The majority
      of the hot-spot areas were identified to be vehicle-related workshops, fuel
      stations and road junctions. The most polluted hot-spot in the study area was
      located in soils close to a car battery processing workshop in the southwestern
      part of Kerman city, with concentrations of Cd (0.32 mg/kg), Cr (169 mg/kg), Cu
      (250 mg/kg), Pb (5,780 mg/kg), Sn (27.2 mg/kg) and Zn (178 mg/kg) of 1, 8.5, 8.3,
      230, 13.5 and 3 times more than the relevant mean concentrations in natural
      soils, respectively. Traffic pollution has resulted in significant accumulation
      of heavy metals in soils and sediments, and that level of accumulation varied
      remarkably among elements. Based on X-ray diffraction analysis, most parts of
      soils and sediments of the Kerman basement consist of calcite and clay minerals.
      Abundance of clay minerals and medium to alkaline pH causes low mobility of heavy
      metals in soils of Kerman.

PMID- 21858451
TI  - Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin
      1: a novel mechanism influencing microfibril assembly and function.
AB  - Tissue microfibrils contain fibrillin-1 as a major constituent. Microfibrils
      regulate bioavailability of TGFbeta superfamily growth factors and are
      structurally crucial in the ocular zonule. FBN1 mutations typically cause the
      Marfan syndrome, an autosomal dominant disorder manifesting with skeletal
      overgrowth, aortic aneurysm, and lens dislocation (ectopia lentis). Infrequently,
      FBN1 mutations cause dominantly inherited Weill-Marchesani syndrome (WMS),
      isolated ectopia lentis (IEL), or the fibrotic condition, geleophysic dysplasia
      (GD). Intriguingly, mutations in ADAMTS [a disintegrin-like and metalloprotease
      (reprolysin-type) with thrombospondin type 1 motif] family members phenocopy
      these disorders, leading to recessive WMS (ADAMTS10), WMS-like syndrome
      (ADAMTS17), IEL (ADAMTSL4 and ADAMTS17) and GD (ADAMTSL2). An ADAMTSL2 founder
      mutation causes Musladin-Lueke syndrome, a fibrotic disorder in beagle dogs. The
      overlapping disease spectra resulting from fibrillin-1 and ADAMTS mutations,
      interaction of ADAMTS10 and ADAMTSL2 with fibrillin-1, and evidence that these
      ADAMTS proteins accelerate microfibril biogenesis, constitutes a consilience
      suggesting that some ADAMTS proteins evolved to provide a novel mechanism
      regulating microfibril formation and consequently cell behavior.

PMID- 21858455
TI  - Symptoms of attention-deficit/hyperactivity disorder and social and school
      adjustment: the moderating roles of age and parenting.
AB  - This study examined the associations between symptoms of attention
      deficit/hyperactivity disorder (ADHD) and social and school adjustment (academic
      performance, peer relationships, school social problems) and the moderating roles
      of children's age and maternal parenting (affection and overprotection) in these
      associations. The sample consisted of 2,463 students who were in the first to
      ninth grade in northern Taiwan. Results from the linear mixed models demonstrated
      that ADHD symptoms were inversely associated with academic performance and
      positively associated with social adjustment problems. Further, children's age
      and maternal parenting moderated the associations between ADHD symptoms and
      school and social adjustment. For example, maternal overprotection moderated the
      relation between hyperactivity and negative peer relationships (i.e., difficulty
      forming and maintaining friendships), such that this relation was stronger for
      children who experienced higher levels of overprotection than children who did
      not. Moreover, children's age moderated the association between attention
      problems and decreased academic performance, such that this association was
      stronger for older children and adolescents than for younger children.
      Furthermore, children's age and maternal affection interacted to influence the
      association between attention problems and school social problems (i.e.,
      bullying, aggression, and peer rejection) with maternal affection acting as a
      buffer for older children (grades 4-6) only. These findings are discussed from a
      developmental psychopathology perspective.

PMID- 21858456
TI  - Prader-Willi syndrome and autism spectrum disorders: an evolving story.
AB  - Prader-Willi syndrome (PWS) is well-known for its genetic and phenotypic
      complexities. Caused by a lack of paternally derived imprinted material on
      chromosome 15q11-q13, individuals with PWS have mild to moderate intellectual
      disabilities, repetitive and compulsive behaviors, skin picking, tantrums,
      irritability, hyperphagia, and increased risks of obesity. Many individuals also
      have co-occurring autism spectrum disorders (ASDs), psychosis, and mood
      disorders. Although the PWS 15q11-q13 region confers risks for autism, relatively
      few studies have assessed autism symptoms in PWS or directly compared social,
      behavioral, and cognitive functioning across groups with autism or PWS. This
      article identifies areas of phenotypic overlap and difference between PWS and ASD
      in core autism symptoms and in such comorbidities as psychiatric disorders, and
      dysregulated sleep and eating. Though future studies are needed, PWS provides a
      promising alternative lens into specific symptoms and comorbidities of autism.

PMID- 21858457
TI  - Fluvastatin modulates renal water reabsorption in vivo through increased AQP2
      availability at the apical plasma membrane of collecting duct cells.
AB  - X-linked nephrogenic diabetes insipidus (XNDI), a severe pathological condition
      characterized by greatly impaired urine-concentrating ability of the kidney, is
      caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene. The
      lack of functional V2Rs prevents vasopressin-induced shuttling of aquaporin-2
      (AQP2) water channels to the apical plasma membrane of kidney collecting duct
      principal cells, thus promoting water reabsorption from urine to the
      interstitium. At present, no specific pharmacological therapy exists for the
      treatment of XNDI. We have previously reported that the cholesterol-lowering drug
      lovastatin increases AQP2 membrane expression in renal cells in vitro. Here we
      report the novel finding that fluvastatin, another member of the statins family,
      greatly increases kidney water reabsorption in vivo in mice in a vasopressin
      independent fashion. Consistent with this observation, fluvastatin is able to
      increase AQP2 membrane expression in the collecting duct of treated mice.
      Additional in vivo and in vitro experiments indicate that these effects of
      fluvastatin are most likely caused by fluvastatin-dependent changes in the
      prenylation status of key proteins regulating AQP2 trafficking in collecting duct
      cells. We identified members of the Rho and Rab families of proteins as possible
      candidates whose reduced prenylation might result in the accumulation of AQP2 at
      the plasma membrane. In conclusion, these results strongly suggest that
      fluvastatin, or other drugs of the statin family, may prove useful in the therapy
      of XNDI.

PMID- 21858458
TI  - Morphine induces splenocyte trafficking into the CNS.
AB  - Opioids significantly alter functional responses of lymphocytes following
      activation. The opiate Morphine, alters the Th1 to Th2 response and modulates
      functional responses such as cytolytic activity and T-cell proliferation.
      Although there has been extensive research involving morphine's effects on
      lymphocytes, little is known about the effects morphine has on lymphocyte
      trafficking. The objective of the study was to use in vivo bioluminescent imaging
      to determine morphine's effect on the trafficking pattern of splenocytes
      systemically and into the CNS either in a naive state or following a
      neuroinflammatory stimulus. A neuroinflammatory response was induced by
      intracerebrally administering a DNA IFN-gamma DNA plasmid into morphine-dependent
      or placebo wildtype mice. Mice with or without a neurostimulus received
      adoptively transferred firefly luciferase transgenic splenocytes and imaged.
      Morphine dependence significantly altered the inherent ability of splenocytes to
      traffic into the spleen, and lead to non-directed chaotic trafficking throughout
      the animal, including into the CNS. The morphine-mediated effects on trafficking
      were blocked by the antagonist naltrexone. Morphine dependence intensified
      splenocyte infiltration into the CNS following neuroinflammation induced by IFN
      gamma gene transfer. The study precented determined that morphine severely
      altered the ability of non-activated splenocytes to home to the spleen, inducing
      extrasplenic trafficking thoughout the animal. In addition to altering the
      ability of naive splenocyte to traffic to the spleen, this study demonstrated
      that morphine profoundly exacerbated lymphocyte infiltration into the CNS
      following a neurostimulus.

PMID- 21858459
TI  - The relationship between body mass index and socioeconomic and demographic
      indicators: evidence from Australia.
AB  - OBJECTIVES: This paper explores the association of body mass index (BMI) with
      socioeconomic and demographic factors using data from the 6th wave of the
      Household, Income and Labour Dynamics in Australia (HILDA) Survey. METHODS: This
      study applies a stereotype logit model (SLM) to assess 10,875 individuals on the
      relationship between BMI and socioeconomic and demographic indicators. RESULTS:
      Aggregate results from the SLM show a positive (and concave) association between
      age and higher BMI. Further, males are more likely than females to have higher
      BMI. Higher BMI is positively associated with long-term health problems, reduced
      prosperity, being married, and being born in Australia and negatively associated
      with possessing a diploma or above. CONCLUSIONS: Results show that there is a
      positive and concave relationship between age and higher BMI. Further, males tend
      to have higher BMI as compared to females. Higher BMI is also positively related
      to long-term health problems, reduced prosperity, being married and being born in
      Australia. Negative association with BMI is observed on those possessing a
      diploma and above.

PMID- 21858460
TI  - Improving health and energy efficiency through community-based housing
      interventions.
AB  - OBJECTIVES: Houses designed for one climate and cultural group may not be
      appropriate for other places and people. Our aim is to find cost-effective ways
      to improve the characteristics of older homes, ill-fitted for New Zealand's
      climate, in order to improve the occupants' health. METHOD: We have carried out
      two community randomised trials, in partnership with local communities, which
      have focused on retrofitted insulation and more effective heating and have two
      other studies under way, one which focuses on electricity vouchers and the other
      on housing hazard remediation. RESULTS: The Housing, Insulation and Health Study
      showed that insulating 1,350 houses, built before insulation was required,
      improved the occupants' health and well being as well as household energy
      efficiency. In the Housing, Heating and Health Study we investigated the impact
      of installing more effective heating in insulated houses for 409 households,
      where there was a child with doctor-diagnosed asthma. Again, the study showed
      significant results in the intervention group; indoor temperatures increased and
      levels of NO(2) were halved. Children reported less poor health, lower levels of
      asthma symptoms and sleep disturbances by wheeze and dry cough. Children also had
      fewer days off school. CONCLUSION: Improving the energy efficiency of older
      housing leads to health improvements and energy efficiency improvements.
      Multidisciplinary studies of housing interventions can create compelling evidence
      to support policies for sustainable housing developments which improve health.

PMID- 21858461
TI  - The health and housing in transition study: a longitudinal study of the health of
      homeless and vulnerably housed adults in three Canadian cities.
AB  - OBJECTIVES: While substantial research has demonstrated the poor health status of
      homeless populations, the health status of vulnerably housed individuals is
      largely unknown. Furthermore, few longitudinal studies have assessed the impact
      of housing transitions on health. The health and housing in transition (HHiT)
      study is a prospective cohort study that aims to track the health and housing
      status of a representative sample of homeless and vulnerably housed single adults
      in three Canadian cities (Toronto, Ottawa, and Vancouver). This paper discusses
      the HHiT study methodological recruitment strategies and follow-up procedures,
      including a discussion of the limitations and challenges experienced to date.
      METHODS: Participants (n = 1,192) were randomly selected at shelters, meal
      programmes, community health centres, drop-in centres, rooming houses, and single
      room occupancy hotels from January to December 2009 and are being re-interviewed
      every 12 months for a 2-year period. RESULTS: At baseline, over 85% of
      participants reported having at least one chronic health condition, and over 50%
      reported being diagnosed with a mental health problem. CONCLUSIONS: Our findings
      suggest that, regardless of housing status, participants had extremely poor
      overall health.

PMID- 21858462
TI  - Telocytes and putative stem cells in the lungs: electron microscopy, electron
      tomography and laser scanning microscopy.
AB  - This study describes a novel type of interstitial (stromal) cell - telocytes
      (TCs) - in the human and mouse respiratory tree (terminal and respiratory
      bronchioles, as well as alveolar ducts). TCs have recently been described in
      pleura, epicardium, myocardium, endocardium, intestine, uterus, pancreas, mammary
      gland, etc. (see www.telocytes.com ). TCs are cells with specific prolongations
      called telopodes (Tp), frequently two to three per cell. Tp are very long
      prolongations (tens up to hundreds of MUm) built of alternating thin segments
      known as podomers (<= 200 nm, below the resolving power of light microscope) and
      dilated segments called podoms, which accommodate mitochondria, rough endoplasmic
      reticulum and caveolae. Tp ramify dichotomously, making a 3-dimensional network
      with complex homo- and heterocellular junctions. Confocal microscopy reveals that
      TCs are c-kit- and CD34-positive. Tp release shed vesicles or exosomes, sending
      macromolecular signals to neighboring cells and eventually modifying their
      transcriptional activity. At bronchoalveolar junctions, TCs have been observed in
      close association with putative stem cells (SCs) in the subepithelial stroma. SCs
      are recognized by their ultrastructure and Sca-1 positivity. Tp surround SCs,
      forming complex TC-SC niches (TC-SCNs). Electron tomography allows the
      identification of bridging nanostructures, which connect Tp with SCs. In
      conclusion, this study shows the presence of TCs in lungs and identifies a TC-SC
      tandem in subepithelial niches of the bronchiolar tree. In TC-SCNs, the synergy
      of TCs and SCs may be based on nanocontacts and shed vesicles.

PMID- 21858463
TI  - Study of canine parvovirus evolution: comparative analysis of full-length VP2
      gene sequences from Argentina and international field strains.
AB  - The continuous emergence of new strains of canine parvovirus (CPV), poorly
      protected by current vaccination, is a concern among breeders, veterinarians, and
      dog owners around the world. Therefore, the understanding of the genetic
      variation in emerging CPV strains is crucial for the design of disease control
      strategies, including vaccines. In this paper, we obtained the sequences of the
      full-length gene encoding for the main capsid protein (VP2) of 11 canine
      parvovirus type 2 (CPV-2) Argentine representative field strains, selected from a
      total of 75 positive samples studied in our laboratory in the last 9 years. A
      comparative sequence analysis was performed on 9 CPV-2c, one CPV-2a, and one CPV
      2b Argentine strains with respect to international strains reported in the
      GenBank database. In agreement with previous reports, a high degree of identity
      was found among CPV-2c Argentine strains (99.6-100% and 99.7-100% at nucleotide
      and amino acid levels, respectively). However, the appearance of a new
      substitution in the 440 position (T440A) in four CPV-2c Argentine strains
      obtained after the year 2009 gives support to the variability observed for this
      position located within the VP2, three-fold spike. This is the first report on
      the genetic characterization of the full-length VP2 gene of emerging CPV strains
      in South America and shows that all the Argentine CPV-2c isolates cluster
      together with European and North American CPV-2c strains.

PMID- 21858464
TI  - Phylogenetic analysis of small ruminant lentivirus (SRLV) in Italian flocks
      reveals the existence of novel genetic subtypes.
AB  - In order to investigate the genetic heterogeneity of small ruminant lentivirus
      (SRLV) isolates in Italy, 55 clinical samples collected between 1998 and 2010
      were analysed. The phylogenetic study was based on analysis of gag-pol sequences.
      Our findings revealed that the SRLVs belonged to the subtype A9 (n = 3, sheep),
      B1 (n = 5, goat), B2 (n = 3, sheep) and E2 (n = 5, goat). Interestingly, 39
      isolates from both sheep and goat, significantly differed from all the other
      SRLVs previously described and formed two separate clusters within genotypes A
      and B tentatively named A11 (n = 27, goat and sheep) and B3 (n = 12, goat and
      sheep), which have never been shown before. These results revealed a marked
      diversity among Italian field SRLV strains which might reflect the absence of any
      systematic control measures.

PMID- 21858465
TI  - Anatomical and functional changes of retina following subretinal injection of
      high-speed fluid.

PMID- 21858466
TI  - Evaluation of the relationship between quality of vision and the visual function
      index in Japanese glaucoma patients.
AB  - BACKGROUND: We compared two types of visual field index including mean deviation
      (MD) and the visual field index (VFI) for assessing the relationship between
      quality of life (QOL) and the loss of visual field in open-angle glaucoma
      patients. METHODS: We examined 336 eyes of 168 consecutive glaucoma patients. All
      participants completed the Japanese version of the 25-item National Eye Institute
      Visual Function Questionnaire (NEI VFQ-25). Visual field testing using the
      Humphrey Field Analyzer (HFA) was performed to obtain both MD and VFI in the
      bilateral eyes of each patient. We defined eyes of better MD or VFI as the better
      eye and the fellow eyes as the worse eye. Visual field data and scores of NEI VFQ
      25 were compared between patients with normal tension glaucoma (NTG) and patients
      with primary open-angle glaucoma (POAG). A single linear regression analysis was
      applied to assess the significance of the relationship between QOL and visual
      field, and to compare the strength of correlations between MD and the VFI. An
      unpaired t test was used for the comparison the data between NTG and POAG.
      RESULTS: A significant relationship was observed between QOL and visual field in
      nine subscales and the composite in both the better eye and the worse eye. The
      relationship was stronger in the better eye than in the worse eye. The
      correlation coefficients of the VFI were slightly higher than those of MD
      overall. The highest correlation coefficients were demonstrated in ten subscales
      and the composite in the better eye of the VFI. Only the score for general vision
      was significantly higher in NTG patients than POAG patients. CONCLUSIONS: A
      significant relationship was found between QOL and both the VFI and MD, but the
      VFI had a marginally better correlation than that of MD. While QOL was better
      related with visual field loss in the better eye than in the worse eye, the
      difference was not large. Not much of a difference was found in the status of QOL
      between NTG patients and POAG patients.

PMID- 21858467
TI  - The PI3K/Akt pathway mediates the expression of type I collagen induced by TGF
      beta2 in human retinal pigment epithelial cells.
AB  - PURPOSE: Transforming growth factor (TGF)-beta is a key mediator of proliferative
      vitreoretinopathy, but the cellular mechanisms by which TGF-beta induces
      extracellular matrix protein (ECM) synthesis are not fully understood. This study
      examined whether the PI3K/Akt pathway is involved in TGF-beta2-induced collagen
      expression in human retinal pigment epithelial cells. METHODS: Human retinal
      pigment epithelial cells ARPE-19 were cultured and stimulated with TGF-beta2. The
      role of the PI3K/Akt pathway was evaluated using the biochemical inhibitor,
      wortmannin. The effect of wortmannin on the expression of type I collagen mRNA
      (COL1A1, COL1A2) induced by TGF-beta2 was evaluated by real-time RT-PCR. The
      effect of wortmannin on the synthesis of type I collagen induced by TGF-beta2 was
      assessed by an immunocytochemical analysis with anti-type I collagen antibody.
      Luciferase reporter assays were performed to examine the effect of wortmannin on
      the transcriptional activities of COL1A2. A luciferase assay using a mutation
      construct of the Smad binding site in COL1A2 promoter (Smad-mut/Luc) was also
      performed to examine the crosstalk between the Smad pathway and the PI3K/Akt
      pathway. The effects of wortmannin on the transcriptional activity of Smad3 were
      also examined using CAGA12-Luc. Moreover, the effect of wortmannin on TGF-beta2
      induced Smad7 mRNA expression was evaluated. RESULTS: The biochemical blockade of
      PI3K/Akt activation inhibited TGF-beta2-induced type I collagen mRNA expression
      and type I collagen synthesis. The blockade of PI3K/Akt pathway inhibited the
      increase in COL1A2 promoter activities when induced by TGF-beta2 and reduced TGF
      beta2 induction of Smad-mut/Luc promoter activity and CAGA12-Luc activity.
      Moreover, wortmannin increased the TGF-beta2-induced Smad7 mRNA expression
      levels. CONCLUSIONS: The PI3K/Akt pathway plays a role in relaying the TGF-beta2
      signal to induce type I collagen synthesis in the retinal pigment epithelium
      through Smad-dependent and Smad-independent pathways.

PMID- 21858468
TI  - Outcomes of different management options for malignant glaucoma: a retrospective
      study.
AB  - BACKGROUND: To assess the outcomes of the various medical and surgical treatment
      options for malignant glaucoma. METHODS: Design Retrospective, comparative case
      series. Participants Twenty-four eyes of 21 patients with malignant glaucoma.
      Intervention Nine eyes were treated medically. Twenty-one eyes underwent surgery,
      15 of which had the full vitrectomy-(phaco)-iridectomy-zonulectomy procedure.
      Main outcome measures Intraocular pressure (IOP), best-corrected visual acuity
      (BCVA) and number of glaucoma medications were measured. RESULTS: The relapse
      rate was 100% after medical therapy, 75% after a Yag laser capsulotomy and a
      hyaloidotomy, 75% after a conventional vitrectomy and 66% after an anterior
      vitrectomy in combination with an iridectomy-zonulectomy. All patients who
      underwent a full vitrectomy combined with an iridectomy and a zonulectomy (and
      phacoemulsification if phakic) had postoperative relief of malignant glaucoma
      without relapse within the follow-up period. After this vitrectomy-tunnel
      technique, the IOP ranged from 10 to 22 mmHg (mean 16 mmHg) after a mean follow
      up of 61 days. Mean BCVA improved by 5 Early Treatment Diabetic Retinopathy Study
      (ETDRS) lines, and mean number of glaucoma medications decreased from two to one.
      CONCLUSION: Complete vitrectomy combined with iridectomy and zonulectomy (and
      phacoemulsification, if applicable) most successfully managed aqueous
      misdirection syndrome in our retrospective case series.

PMID- 21858469
TI  - [Registration procedure for incidents with implants].
AB  - Incidents involving implants, whether there is a break in the osteosynthesis
      plate or a synthetic inlay of an endoprosthesis, are incidents with mostly severe
      repercussions for the patient with immediate and delayed effects for the clinic
      involved and the manufacturer.

PMID- 21858470
TI  - QTL underlying the resistance to soybean aphid (Aphis glycines Matsumura) through
      isoflavone-mediated antibiosis in soybean cultivar 'Zhongdou 27'.
AB  - Soybean aphid (Aphis glycines Matsumura) results in severe yield loss of soybean
      in many soybean-growing countries of the world. A few loci have been previously
      identified to be associated with the aphid resistance in soybean. However, none
      of them was via isoflavone-mediated antibiosis process. The aim of the present
      study was to conduct genetic analysis of aphid resistance and to identify
      quantitative trait loci (QTL) underlying aphid resistance in a Chinese soybean
      cultivar with high isoflavone content. One hundred and thirty F(5:6) derived
      recombinant inbred lines from the 'Zhongdou 27' * 'Jiunong 20' cross were used.
      Two QTL were directly associated with resistance to aphid as measured by aphid
      damage index. qRa_1, close to Satt470 on soybean linkage group (LG) A2
      (chromosome 8), was consistently detected for 3- and 4-week ratings and explained
      a large portion of phenotypic variations ranging from 25 to 35%. qRa_2, close to
      Satt144 of LG F (chromosome 13), was detected for 3- and 4-week ratings and could
      explain 7 and 11% of the phenotypic variation, respectively. These two QTL were
      highly associated with high isoflavone content and both positive alleles were
      derived from 'Zhongdou 27', a cultivar with higher isoflavone content. The
      results revealed that higher individual or total isoflavones contents in soybean
      lines could protect soybean against aphid attack. These two QTL detected jointly
      provide potential for marker-assisted selection to improve the resistance of
      soybean cultivars to aphid along with the increase of isoflavone content.

PMID- 21858471
TI  - Synthetic polyamines as potential amine oxidase inhibitors: a preliminary study.
AB  - In the last few decades, medicinal chemists have carried out extensive research
      on synthetic polyamines for use as anticancer drugs and multitarget-directed
      ligands in neurodegenerative diseases. The aim of this study was to evaluate the
      effect of some synthetic polyamines as inhibitors of two new potential targets,
      human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP
      1) and monoamine oxidases B (MAO B), enzymes involved in various multi-factorial
      diseases such as Alzheimer's disease. N,N'-Dibenzyl-dodecane-1,12-diamine (Bis
      Bza-Diado), a newly synthesised compound, and ELP 12, a muscarinic cholinergic
      M(2) receptor antagonist, were found to behave as reversible and mixed non
      competitive inhibitors of both amine oxidases (dissociation constants of about
      100 MUM). ELP 12 was found to be more selective for SSAO/VAP-1. Combining kinetic
      and structural approaches, the binding mode of ELP 12 to SSAO/VAP-1 was
      investigated. ELP 12 may bind at the entrance of the active site channel by ionic
      interactions with ASP446 and/or ASP180; one end of the polyamine may be
      accommodated inside the channel, reaching the TPQ cofactor area. The binding of
      ELP 12 induces rearrangement of the secondary structure of the enzyme and impedes
      substrate entry and/or product release and catalysis. These structural data
      reveal that the entrance and the first part of the SSAO/VAP-1 channel may be
      considered as a new target area, or a "secondary binding site", for modulators of
      human SSAO/VAP-1 activity. These results indicate ELP 12 and Bis-Bza-Diado as new
      "skeletons" for the development of novel SSAO/VAP-1 and MAO B inhibitors.

PMID- 21858472
TI  - Melanoma: a new landmark in targeted oncology.

PMID- 21858473
TI  - Multiple traumatic insemination events reduce the ability of bed bug females to
      maintain water balance.
AB  - To examine how traumatic insemination, a wounding process to females inflicted by
      males during copulation, reduces the longevity of females of the bedbug, Cimex
      lectularius, we assessed if multiple bouts of mating impact water relations of
      females by measuring net transpiration water loss rates. Our studies show that
      net transpiration rate of females correlates with frequency of mating (small
      increase after exposure to low numbers of males; large increase after exposure to
      large numbers of males), and this is reflected by reduced female survivorship for
      as much as 22 days at 75% RH, 25 degrees C. Water loss occurs up to 28% more
      rapidly in females after being held with large groups of males. Females that were
      exposed to males having their paramere removed, females exposed only to other
      females, and females kept in isolation (unmated) exhibited no reduction in
      ability to retain water, indicating that traumatic insemination was responsible
      for the net transpiration rate increase. Mechanical piercing of the female's
      abdominal wall leads to increased net transpiration rates for longer periods than
      puncturing the ectospermalege (regular mating site), implying that inaccurate
      copulation by males is extremely detrimental to the water balance of females and
      that the ectospermalege is uniquely modified to seal off more quickly to prevent
      excess water loss. Mating frequency and the associated increased water loss is
      considerably reduced by the addition of bed bug alarm pheromone components. Thus,
      females experience elevated water stress due to traumatic insemination,
      especially at high levels and when males fail to pierce the ectospermalege, and
      water loss prevention, likely by more rapid sealing of the wound, is a novel
      function of the ectopsermalege.

PMID- 21858474
TI  - An epidemiological study of alendronate-related osteonecrosis of the jaws. A case
      series from the south-east of Scotland with attention given to case definition
      and prevalence.
AB  - A close case study series of alendronate-associated osteonecrosis of the jaws
      (AONJ) is presented. A consistency of case definition with a minimal reporting
      requirement was attempted as recommended by the task force of the American
      Society for Bone and Mineral Research. A hierarchy of evidence focussing on 7
      categories of interest was included for each case. A further 7 categories were
      added by the authors and completed where possible. The patients were drawn from a
      discrete population of 900,000 from the south-east of Scotland. The prescribing
      of drugs to this population was monitored by a government agency, the Information
      Services Office of the National Health Service of Scotland. The daily or weekly
      standard doses of alendronate prescribed to this population were recorded, thus
      allowing a calculation of the drug patient years (DPYs). The number of cases of
      AONJ, when computed against the cumulative year-on-year DPYs for alendronate,
      suggests an incidence of AONJ per DPYs of <0.004% for age-related or hormone
      related osteoporosis. This increased to >0.1% when alendronate was prescribed as
      a prophylaxis against glucocorticosteroid-induced osteoporosis.

PMID- 21858475
TI  - Variations in local elastic modulus along the length of the aorta as observed by
      use of a scanning haptic microscope (SHM).
AB  - Variations in microscopic elastic structures along the entire length of canine
      aorta were evaluated by use of a scanning haptic microscope (SHM). The total
      aorta from the aortic arch to the abdominal aorta was divided into 6
      approximately equal segments. After embedding the aorta in agar, it was cut into
      horizontal circumferential segments to obtain disk-like agar portions containing
      ring-like samples of aorta with flat surfaces (thickness, approximately 1 mm).
      The elastic modulus and topography of the samples under no-load conditions were
      simultaneously measured along the entire thickness of the wall by SHM by using a
      probe with a diameter of 5 MUm and a spatial resolution of 2 MUm at a rate of 0.3
      s/point. The elastic modulus of the wall was the highest on the side of the
      luminal surface and decreased gradually toward the adventitial side. This
      tendency was similar to that of the change in the elastin fiber content. During
      the evaluation of the mid-portion of each tunica media segment, the highest
      elastic modulus (40.8 +/- 3.5 kPa) was identified at the thoracic section of the
      aorta that had the highest density of elastic fibers. Under no-load conditions,
      portions of the aorta with high elastin density have a high elastic modulus.

PMID- 21858476
TI  - Comradery, community, and care in military medical ethics.
AB  - Medical ethics prohibits caregivers from discriminating and providing
      preferential care to their compatriots and comrades. In military medicine,
      particularly during war and when resources may be scarce, ethical principles may
      dictate priority care for compatriot soldiers. The principle of nondiscrimination
      is central to utilitarian and deontological theories of justice, but
      communitarianism and the ethics of care and friendship stipulate a different set
      of duties for community members, friends, and family. Similar duties exist among
      the small cohesive groups that typify many military units. When members of these
      groups require medical care, there are sometimes moral grounds to treat
      compatriot soldiers ahead of enemy or allied soldiers regardless of the severity
      of their respective wounds.

PMID- 21858477
TI  - In vitro studies on the sexual maturation of the bovine lungworm Dictyocaulus
      viviparus during the development of preadult larvae to adult worms.
AB  - The bovine lungworm Dictyocaulus viviparus is one of the most important parasites
      in grazing cattle. However, not much is known about morphology and molecular
      aspects of sexual maturation occurring during development of preadult larvae (L5)
      to adults. Since studies in the pulmonary compartments are infeasible, an in
      vitro cultivation method was established. The study was conducted with L5 during
      in vitro cultivation, assessing longitudinal growth and sexual maturation. Best
      results were achieved with RPMI-1640 medium with L-glutamine, 50% fetal bovine
      serum, amphotericin B (0.25 mg/ml), penicillin (10,000 U/ml), and streptomycin
      (10 mg/ml) at 39 degrees C and 5% atmospheric CO2. During cultivation,
      individuals grew from an average length of 4.64 to 9.88 mm independent of their
      density per setup. Regarding sexual maturation, female individuals started to lay
      eggs, whereas the testes of male individuals were filled with spermatozoa.
      Consequently, adult female and adult male worms developed. However, no copulation
      was observable and eggs did not embryonate. Development was further investigated
      by quantitative real-time PCR transcriptional analysis of major sperm protein
      (msp) and vitellogenin (vit) representing male and female sexual development,
      respectively. Male msp transcription peaked after 5 days of cultivation
      [corresponding to 20 days post infection (dpi)] and decreased gradually
      afterwards. Female vit transcription showed the highest rate after 15 days of
      cultivation (30 dpi), however it never reached the transcription rate in female
      adults isolated from the host. All in all, the present study gives not only
      insights into morphological differentiation but provides data lightening
      molecular aspects of sexual maturation in D. viviparus.

PMID- 21858478
TI  - Morphological and molecular biological characterization of Pleistophora
      aegyptiaca sp. nov. infecting the Red Sea fish Saurida tumbil.
AB  - One hundred three out of 225 (45.8%) of the Red Sea fish Saurida tumbil were
      infected with microsporidian parasites. The infection was recorded as tumor-like
      masses (whitish macroscopic cysts) or xenomas often up to 2 cm in diameter and
      embedded in the peritoneal cavity. Generally, the infection was increased during
      winter 63.8% (86 out of 135) and fall to 18.9% (17 out of 90) in summer. Light
      microscopic study revealed that xenomas were encapsulated by a fibrous layer
      encircling numerous sporophorous vesicles filled with mature spores measuring 1.7
      +/- 0.6 (1.5-2.7 MUm) * 1.5 +/- 0.3 MUm (1.2-1.8 MUm) in size. Ultrastructural
      microscopic study showed the presence of smooth membranes of the sarcoplasmic
      reticulum forming a thick, amorphous coat surrounding various developmental
      stages of the parasite. The various recognizable stages of the parasite were
      uninuclear, binucleated, and multinucleated meronts followed by detachment of the
      plasmalemma of the sporont from the sporophorous vesicle producing sporoblasts.
      Mature spores consist of a spore coat and spore contents. The spore contents
      consist of the uninucleated sporoplasm and a posterior vacuole located at the
      posterior end. The polar tube consists of a straight shaft and a coiled region
      (26-32 coils) arranged in many rows along the inside periphery of the spore. The
      polaroplast consisted of an anterior region of closely and loosely packed
      membranes. Molecular analysis based on the small subunit rDNA gene was performed
      to determine the phylogenetic position of the present species. The percentage
      identity between this species and a range of other microsporidia predominantly
      from aquatic hosts demonstrated a high degree of similarity (>92%) with eight
      Pleistophora species. Comparison of the nucleotide sequences and divergence
      showed that the sequence of the present microsporidium was most similar to that
      of Pleistophora anguillarum (99.8% identity) differing in 13 nucleotide
      positions. So, the present species was recorded and phylogenetically positioned
      as a new species of Pleistophora.

PMID- 21858479
TI  - Larvicidal activity of lignans from Phryma leptostachya L. against Culex pipiens
      pallens.
AB  - The larvicidal activity of crude petroleum ether, ethyl acetate, and methanol
      extracts of the whole plants of Phryma leptostachya L. was assayed for its
      toxicity against the early fourth instar larvae of Culex pipiens pallens. The
      larval mortality was observed after 24 h of exposure. Among three solvent
      extracts from Phyrma leptostachya L., the petroleum ether extract exhibited the
      best larvicidal activity. The corresponding LC50 values of petroleum ether, ethyl
      acetate, and methanol extracts were 3.23, 5.23, and 61.86 ppm against the early
      fourth instar larvae of Culex pipiens pallens. The petroleum ether extract was
      successively subjected to column chromatography and preparative high performance
      liquid chromatography, and yielded the three lignans, phrymarolin-I, haedoxane A,
      and haedoxane E, which were isolated and identified as new mosquito larvicidal
      compounds. Phrymarolin-I, haedoxane A, and haedoxane E showed high larvicidal
      activity, for which the lethal doses LC50 were estimated at 1.21, 0.025, and 0.15
      ppm against the early fourth instar larvae of Culex pipiens pallens,
      respectively. The structures were elucidated by analyses of IR, UV, MS, and NMR
      spectral data. This is the first report on the mosquito larvicidal activity of
      the three compounds, phrymarolin-I, haedoxane A, and haedoxane E from Phyrma
      leptostachya L.

PMID- 21858481
TI  - Caudate body (CB) sign: new early CT sign of hyperacute anterior cerebral
      circulation infarction.
AB  - This case series describes the caudate body (CB) sign noted in computed
      tomography (CT) scans of patients who presented to the Emergency Department (ED)
      clinically manifesting symptoms suggestive of anterior cerebral circulation
      infarction. This sign has the advantage of early appearance, side-to-side
      comparison, and high conspicuity. Two of the presented cases demonstrate the CB
      sign in the absence of other established signs typically seen with early cerebral
      infarction. Five additional cases demonstrate this sign in conjunction with
      previously described criteria. The CB sign may allow earlier detection of
      hyperacute infarction leading to more rapid initiation of thrombolytics to
      minimize ischemic injury.

PMID- 21858480
TI  - Erratum to: inhibition of triclabendazole metabolism in vitro by ketoconazole
      increases disruption to the tegument of a triclabendazole-resistant isolate of
      Fasciola hepatica.
AB  - A study has been carried out to investigate whether the action of triclabendazole
      (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The
      cytochrome P450 (CYP 450) enzyme pathway was inhibited using ketoconazole (KTZ)
      to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ
      action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were
      used for these experiments. The CYP 450 system was inhibited by a 2-h pre
      incubation in ketoconazole (40 MUM), then incubated for a further 22 h in NCTC
      medium containing either KTZ, KTZ + nicotinamide adenine dinucleotide phosphate
      (NADPH) (1 nM), KTZ + NADPH + TCBZ (15 MUg/ml), or KTZ + NADPH + triclabendazole
      sulphoxide (TCBZ.SO; 15 MUg/ml). Changes to fluke ultrastructure following drug
      treatment and metabolic inhibition were assessed using transmission electron
      microscopy. After treatment with either TCBZ or TCBZ.SO on their own, there was
      greater disruption to the TCBZ-susceptible than TCBZ-resistant isolate. However,
      co-incubation with KTZ + TCBZ, but more particularly KTZ + TCBZ.SO, led to more
      severe changes to the TCBZ-resistant isolate than with each drug on its own: for
      example, there was severe swelling of the basal infolds and their associated
      mucopolysaccharide masses, accompanied by an accumulation of secretory bodies
      just below the apex. Golgi complexes were greatly reduced or absent in the
      tegumental cells and the synthesis, production, and transport of secretory bodies
      were badly disrupted. With the TCBZ-susceptible Cullompton isolate, there was
      limited potentiation of drug action. The results support the concept of altered
      drug metabolism in TCBZ-resistant flukes and this process may play a role in the
      development of drug resistance.

PMID- 21858482
TI  - Asthma and pregnancy.
AB  - Asthma is probably the most common serious medical disorder that may complicate
      pregnancy. A third of pregnant women with asthma will experience worsening of
      their symptoms, a third will see improvement of their symptoms and a third will
      see no change. The primary goal is to maintain optimal control of asthma for
      maternal health and well-being as well as fetal maturation. Vital patient
      education should cover the use of controller medication, avoidance of asthma
      triggers and early treatment of asthma exacerbations. Proper asthma management
      should ideally be started in the preconception period. Since smoking is probably
      the most modifiable risk factor of asthma, pregnant woman should avoid active and
      passive smoking. Acute asthma exacerbation during the first trimester is
      associated with an increased risk of congenital malformations. Poorly controlled
      asthma is associated with low birth weight, preeclampsia, and preterm birth.
      Medications used for asthma control in the non-pregnant population are generally
      the same in pregnancy with a few exceptions. Inhaled corticosteroids (ICS) are
      the preferred controller therapy. Budesonide is the preferred ICS. Long-acting B
      agonists (LABA) are the preferred add-on therapy to medium to high dose ICS.
      Major triggers for asthma exacerbations during pregnancy are viral infections and
      ICS nonadherence.

PMID- 21858483
TI  - Distribution of TRPC6 in the cerebrospinal fluid-contacting nucleus of rat brain
      parenchyma and its expression in morphine dependence and withdrawal.
AB  - To investigate the role of cerebrospinal fluid contacting nucleus (CSF-CN) and
      the changes of TRPC6 expression in morphine dependence and withdrawal. Male
      Sprague-Dawley rats (250 +/- 50 g) were randomly divided into four groups: the
      normal group (N); the saline group (S); the morphine dependence group (D); the
      morphine withdrawal group (W). All animals in each group were tested the morphine
      withdrawal-like behavioral signs by total withdrawal scores. Double-labeled
      immunofluorescent technique and laser scanning confocal microscopy were used to
      identify the expression of TRPC6 in CSF-CN. TRPC6 labeled neurons were found in
      CSF-CN and the number of CB-HRP/TRPC6 double labeled neurons in CSF-CN
      significantly increased. TRPC6 existed in CSF-CN of the normal rats and its
      expression in morphine dependence and withdrawal increased. CSF-CN might
      participate in the development of morphine dependence and withdrawal by the up
      regulated expression of TRPC6.

PMID- 21858484
TI  - [T-cell costimulation. Basic mechanisms and new aspects].
AB  - Recent publications regarding the function of the T-cell costimulators CD226 and
      TIGIT as well as the identification of the new costimulatory ligand VISTA are of
      great interest for an understanding of autoimmune diseases. Both systems display
      striking similarities to the well-established costimulators CD28/CTLA-4 and PD-1.

PMID- 21858485
TI  - [Maurice Raynaud (1834-1881) and the syndrome named after him].
AB  - Approximately 150 years ago Maurice Raynaud described in his doctoral thesis a
      set of symptoms characterized by intermittent pallor and cyanosis of the
      extremities which in severe cases could lead to the development of gangrene.
      Because the symptoms could be triggered by spasms in small blood vessels the
      exclusion of an organic vascular disease is a prerequisite of the diagnosis.
      Raynaud had not yet recognized that this often observed syndrome could sometimes
      be advance or initial symptoms of a severe general disease. This is the reason
      why nowadays these are referred to as primary and secondary Raynaud syndromes.
      Simultaneously to his doctoral thesis Raynaud had submitted his PhD thesis with
      two noteworthy publications on the history of medicine. His postdoctoral thesis
      encompassed a comprehensive study of the"efferent process". Raynaud worked in
      various Paris clinics, occupied himself with many problems and was considered to
      be a good academic teacher. For political reasons he was neither promoted to
      professor nor did he receive a chair in the history of medicine.

PMID- 21858486
TI  - [Amendment of the structural quality for inpatient rheumatology. A forward
      looking concept].
AB  - In 2010 a total of 9 guidelines on structural quality were endorsed by the
      Association of Rheumatology Clinics in Germany (VRA). These 9 structural criteria
      replace the regulations published in 2002 and were elaborated with the support of
      the German Rheumatology League. With guideline number 9 even the structural
      requirements for university hospitals are defined for the first time.Along with
      taking part in the quality project "Kobra" (continuous outcome benchmarking in
      rheumatology inpatient treatment) compliance with the new structural criteria
      constitutes a prerequisite for acquiring a quality certificate, which is awarded
      by an external institution.By this means the VRA sets the stage for its members
      to be prepared for future challenges and quality competition among hospitals.
      Furthermore, the provision of a high quality treatment for chronically diseased
      patients in rheumatology clinics will be effectively supported.

PMID- 21858487
TI  - [Hemato-oncological diseases. Associated rheumatic symptoms].
AB  - Paraneoplastic syndromes are observed in up to 8% of tumor patients. These
      disorders arise from tumor secretion of hormones, peptides, growth factors or
      cytokines or from immune cross-reactivity between malignant and normal tissues.
      Among many others paraneoplastic syndromes may also affect the rheumatologic
      system resulting in various musculoskeletal symptoms and/or syndromes. On the
      other hand, mainly hematological or lymphoproliferative diseases may also cause
      rheumatic symptoms by cell invasion or when affecting cellular elements of blood
      or the coagulation system. The aim of this article is to provide an overview of
      the various associations between rheumatic symptoms and hemato-oncological
      diseases which might be of importance in clinical practice.

PMID- 21858488
TI  - [Gastrointestinal tumors. Clinical manifestations of paraneoplastic rheumatic
      symptoms].
AB  - Paraneoplastic syndromes, as syndromes associated with malignancy, can present
      unrelated to tumor invasion or metastases. They can occur with varying clinical
      appearance and are often indistinguishable from idiopathic rheumatic symptoms.
      Some musculoskeletal disorders are more associated with malignancies. The therapy
      of rheumatic syndromes can itself have an effect on the tumorigenic process. The
      clinical severity of paraneoplastic rheumatic symptoms can in many cases aid in
      the assessment of tumor activity and the response to therapy. While generally an
      extensive search for occult malignancies in every older rheumatoid patient in
      cases with no indications of malignancy is not advisable, knowledge of rheumatic
      symptoms associated with malignancies aids in the important early detection of
      tumors, while avoiding unnecessary examinations.

PMID- 21858489
TI  - After out-of-home mental health treatment: atypical antipsychotic medication use
      and the probability of returning to treatment.
AB  - Florida Medicaid claims data were used to assess antipsychotic medication use
      among children after therapeutic out-of-home mental health treatment. Fifty
      percent of youth received antipsychotics after the treatment episode, but
      differences exist across age, gender, and racial groups. Utilization was higher
      among males and youth ages 6-12, while blacks were less likely to be prescribed
      antipsychotics than whites. Youth receiving antipsychotics were less likely to
      return to out-of-home treatment within 6 months. However, among youth receiving
      antipsychotic medications, a higher medication possession ratio was not
      associated with the likelihood of returning to treatment. Such patterns require
      further investigation to determine whether they indicate inadequate treatment for
      some youth.

PMID- 21858491
TI  - Tafluprost: a novel prostaglandin analog for treatment of glaucoma.
AB  - OBJECTIVE: The objective of this review is to evaluate the safety and efficacy of
      tafluprost, a fluoroprostaglandin receptor analog, for reduction of intraocular
      pressure in open angle glaucoma and ocular hypertension. METHODS: A search of
      published literature was performed on the PubMed database using the search term
      "tafluprost." The literature search identified 48 publications, including
      clinical and preclinical studies, from 2003 to 2011. From these ressults,
      articles available in the English language and in full text were selected and
      systematically reviewed by the authors. RESULTS: Recent studies have shown that
      tafluprost is an effective IOP-lowering medication. Evidence based medicine also
      reveals that tafluprost is safe and well-tolerated. Preservative-free tafluprost
      is as potent as the preserved formulation, but with fewer and milder ocular
      surface side effects. CONCLUSION: Since its introduction in 2008, initial studies
      have demonstrated that preserved and preservative-free tafluprost formulations
      have proven efficacy and safety in the treatment of glaucoma and ocular
      hypertension. Larger studies with longer follow-up are needed to assess long-term
      safety, efficacy, and tolerability compared with other prostaglandin analogs used
      for treating glaucoma.

PMID- 21858490
TI  - How do health insurance loading fees vary by group size?: implications for
      Healthcare reform.
AB  - The health insurance loading fee represents the portion of the premium above the
      expected amount of medical care expenditures paid by the insurance company. The
      size of the loading fees and how they vary by employer group size have important
      implications for health policy given the recent passage of the Patient Protection
      and Affordable Care Act. Despite their policy relevance, there is surprisingly
      little empirical evidence on the magnitude and the determinants of health
      insurance loading fees. This paper provides estimates of the loading fees by firm
      size using data from the confidential Medical Expenditure Panel Survey Household
      Component-Insurance Component Linked File. Overall, we find an inverse
      relationship between employer group size and loading fees. Firms of up to 100
      employees face similar loading fees of approximately 34%. Loads decline with firm
      size and are estimated to be on average 15% for firms with more than 100
      employees, but less than 10,000 employees, and 4% for firms with more than 10,000
      workers.

PMID- 21858492
TI  - Biological souring and mitigation in oil reservoirs.
AB  - Souring in oil field systems is most commonly due to the action of sulfate
      reducing prokaryotes, a diverse group of anaerobic microorganisms that respire
      sulfate and produce sulfide (the key souring agent) while oxidizing diverse
      electron donors. Such biological sulfide production is a detrimental, widespread
      phenomenon in the petroleum industry, occurring within oil reservoirs or in
      topside processing facilities, under low- and high-temperature conditions, and in
      onshore or offshore operations. Sulfate reducers can exist either indigenously in
      deep subsurface reservoirs or can be "inoculated" into a reservoir system during
      oil field development (e.g., via drilling operations) or during the oil
      production phase. In the latter, souring most commonly occurs during water
      flooding, a secondary recovery strategy wherein water is injected to re
      pressurize the reservoir and sweep the oil towards production wells to extend the
      production life of an oil field. The water source and type of production
      operation can provide multiple components such as sulfate, labile carbon sources,
      and sulfate-reducing communities that influence whether oil field souring occurs.
      Souring can be controlled by biocides, which can non-specifically suppress
      microbial populations, and by the addition of nitrate (and/or nitrite) that
      directly impacts the sulfate-reducing population by numerous competitive or
      inhibitory mechanisms. In this review, we report on the diversity of sulfate
      reducers associated with oil reservoirs, approaches for determining their
      presence and effects, the factors that control souring, and the approaches (along
      with the current understanding of their underlying mechanisms) that may be used
      to successfully mitigate souring in low-temperature and high-temperature oil
      field operations.

PMID- 21858493
TI  - Gene cloning, expression, and characterization of a novel acetaldehyde
      dehydrogenase from Issatchenkia terricola strain XJ-2.
AB  - Acetaldehyde is a known mutagen and carcinogen. Active aldehyde dehydrogenase
      (ALDH) represents an important mechanism for acetaldehyde detoxification. A yeast
      strain XJ-2 isolated from grape samples was found to produce acetaldehyde
      dehydrogenase with a high activity of 2.28 U/mg and identified as Issatchenkia
      terricola. The enzyme activity was validated by oxidizing acetaldehyde to acetate
      with NAD(+) as coenzyme based on the headspace gas chromatography analysis. A
      novel acetaldehyde dehydrogenase gene (ist-ALD) was cloned by combining
      SiteFinding-PCR and self-formed adaptor PCR. The ist-ALD gene comprised an open
      reading frame of 1,578 bp and encoded a protein of 525 amino acids. The predicted
      protein of ist-ALD showed the highest identity (73%) to ALDH from Pichia angusta.
      The ist-ALD gene was expressed in Escherichia coli, and the gene product (ist
      ALDH) presented a productivity of 442.3 U/mL cells. The purified ist-ALDH was a
      homotetramer of 232 kDa consisting of 57 kDa-subunit according to the SDS-PAGE
      and native PAGE analysis. Ist-ALDH exhibited the optimal activity at pH 9.0 and
      40 degrees C, respectively. The activity of ist-ALDH was enhanced by K(+),
      NH4(+), dithiothreitol, and 2-mercaptoethanol but strongly inhibited by Ag(+),
      Hg(2+), Cu(2+), and phenylmethyl sulfonylfluoride. In the presence of NAD(+), ist
      ALDH could oxidize many aliphatic, aromatic, and heterocyclic aldehydes,
      preferably acetaldehyde. Kinetic study revealed that ist-ALDH had a k (cat) value
      of 27.71/s and a k (cat)/K (m) value of 26.80 * 10(3)/(mol s) on acetaldehyde,
      demonstrating ist-ALDH, a catalytically active enzyme by comparing with other
      ALDHs. These studies indicated that ist-ALDH was a potential enzymatic product
      for acetaldehyde detoxification.

PMID- 21858494
TI  - Antibacterial property and mechanism of a novel Pu-erh tea nanofibrous membrane.
AB  - Pu-erh tea is made via a natural fermentation process. In this study, Pu-erh tea
      was used as a raw material for nanomaterials preparation and as an antibacterial
      agent. Antibacterial activities on Escherichia coli of Pu-erh tea, Pu-erh tea
      powder (PTP) of different sizes, and Pu-erh tea residual powder were firstly
      determined, respectively. With polyvinyl alcohol as the carrier, through an
      electrospinning technique, different kinds of nanofibrous membranes were obtained
      from the extract of Pu-erh tea and nano-PTP (NPTP), and their antibacterial
      properties and mechanism against E. coli were evaluated. The results showed
      better antibacterial activity with smaller PTP particles, the nano-sized
      particles had the best effects, and the MIC of NPTP was 13.5 mg/mL. When NPTP was
      in nanofibrous membranes, the antibacterial activity decreased slightly, but
      increased with modification by ZnO. Pu-erh tea in nanofibrous membranes damaged
      the E. coli cell membranes and caused leakage of K(+) and enzymes. What is more
      is that damage of the cell walls led to the leakage of fluorescent proteins from
      enhanced green fluorescence protein-expressing E. coli. These results indicate
      that the Pu-erh tea nanofibrous membranes had good antibacterial activities
      against E. coli, which may provide a promising application of novel antibacterial
      materials.

PMID- 21858495
TI  - Label-free quantification of cystatin C as an improved marker for renal failure.
AB  - A label-free biosensor has been developed, allowing quantification of cystatin C
      in human serum. This was achieved by using reflectometric interference
      spectroscopy as detection method. Cystatin C is a small serum protein that allows
      detection of renal failure more reliably than established parameters as
      creatinine. The protein was immobilized on the surface of a glass transducer,
      forming the sensitive layer of the sensor chip. Based on a binding-inhibition
      assay, two different types of monoclonal cystatin C antibodies were compared, by
      their behavior and their obtained working range in buffer and serum as matrix.
      Both antibodies allowed quantification of the protein in serum as matrix within
      the required clinical ranges of 0.53-1.02 mg/L. Detected recovery rates are in a
      range between 84.8% and 116.1%. The developed sensor shows high inner chip
      reproducibility and low cross-sensitivity.

PMID- 21858496
TI  - Analysis of doxorubicin uptake in single human leukemia K562 cells using
      capillary electrophoresis coupled with laser-induced fluorescence detection.
AB  - The doxorubicin (DOX) uptake in single human leukemia K562 cells with changes in
      both drug dosage and exposure period was studied using capillary electrophoresis
      (CE) coupled with laser-induced fluorescence (LIF) detection. The cells were
      treated with DOX at different concentrations (1, 3, 10, 20, 30, and 50 MUM) and
      for different exposure times (1, 3, 5, 24, and 48 h). At least 20 cells were
      analyzed for each DOX-treated cell population. A marked heterogeneity in DOX
      uptake among single cells was observed, because the relative standard deviation
      of the uptake of DOX by single cells ranged from 24.0% to 61.1% within each cell
      population. The cell-to-cell heterogeneity in DOX uptake first decreased and then
      became constant with increasing drug concentration, but it did not exhibit
      regular variation with increasing exposure time. The mean DOX uptake was a linear
      function of drug concentration (r>=0.9667). In terms of the correlation with
      exposure time, the mean DOX uptake reached its maximum at 3 h for the cell
      populations treated with 1-10 MUM DOX, while it kept increasing during 48 h
      exposure of cell populations to 20-50 MUM DOX. Because it eliminates DOX
      fluorescence quenching and sample loss, the CE-LIF method directly detects the
      true DOX uptake by single cells, and thus presents accurate information on both
      the cell-to-cell heterogeneity in DOX uptake and the patterns of DOX uptake in
      K562 cells as functions of drug concentration and exposure time.

PMID- 21858497
TI  - Cadmium determination in natural waters at the limit imposed by European
      legislation by isotope dilution and TiO2 solid-phase extraction.
AB  - The cadmium content in surface water is regulated by the last European Water
      Framework Directive to a maximum between 0.08 and 0.25 MUg L(-1) depending on the
      water type and hardness. Direct measurement of cadmium at this low level is not
      straightforward in real samples, and we hereby propose a validated method capable
      of addressing cadmium content below MUg L(-1) level in natural water. It is based
      on solid-phase extraction using TiO(2) nanoparticles as solid sorbent (0.05 g
      packed in mini-columns) to allow the separation and preconcentration of cadmium
      from the sample, combined to direct isotope dilution and detection by inductively
      coupled plasma mass spectrometry (ID-ICP-MS). The extraction setup is
      miniaturised and semi-automated to reduce risks of sample contamination and
      improve reproducibility. Procedural blanks for the whole measurement process were
      5.3 +/- 2.8 ng kg(-1) (1 s) for 50 g of ultrapure water preconcentrated ten
      times. Experimental conditions influencing the separation (including loading pH,
      sample flow rates, and acid concentration in the eluent) were evaluated. With
      isotope dilution the Cd recovery rate does not have to be evaluated carefully.
      Moreover, the mathematical model associated to IDMS is known, and provides
      transparency for the uncertainty propagation. Our validation protocol was in
      agreement with guidelines of the ISO/IEC 17025 standard (chapter 5.4.5). Firstly,
      we assessed the experimental factors influencing the final result. Secondly, we
      compared the isotope ratios measured after our separation procedure to the
      reference values obtained with a different protocol for the digested test
      material IMEP-111 (mineral feed). Thirdly, we analysed the certified reference
      material BCR-609 (groundwater). Finally, combined uncertainties associated to our
      results were estimated according to ISO-GUM guidelines (typically, 3-4% k = 2 for
      a cadmium content of around 100 ng kg(-1)). We applied the developed method to
      the groundwater and wastewater samples ERM-CA615 and BCR-713, respectively, and
      results agreed with certificate values within uncertainty statements.

PMID- 21858498
TI  - Identification of TLR inducing Th1-responsive Leishmania donovani amastigote
      specific antigens.
AB  - Leishmania is known to elicit Th2 response that causes leishmaniasis progression;
      on the other hand, Th1 cytokines restricts amastigote growth and disease
      progression. In this study, we report the potential of two leishmanial antigens
      (65 and 98 kDa, in combination) which enhance strong macrophage effector
      functions, viz., production of respiratory burst enzymes, nitric oxide, and Th1
      cytokines. The identification of antigens were done by resolving the crude
      soluble antigens on SDS-PAGE and eluted by reverse staining method. Further,
      RAW264.7 macrophages were challenged with eluted antigens, and the innate immune
      response was observed by detecting respiratory burst enzymes, nitric oxide (NOx),
      TNF-alpha, IFN-gamma, IL-12, toll-like receptors (TLRs) gene expression, and TLR
      signaling proteins. These antigens increased the production of nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, NOx, TNF
      alpha, IFN-gamma, IL-12, TLR2, and p38 mitogen-activated protein kinase. These
      antigens also induced human peripheral blood mononuclear cells proliferation and
      Th1 cytokine production. This study concludes that these antigens induce innate
      immune response as well as have prophylactic efficacy.

PMID- 21858499
TI  - In vitro cytokine stimulation assay for glycolipid biosurfactant from Rhodococcus
      ruber: role of monocyte adhesion.
AB  - Glycolipid biosurfactant (GLB) from Rhodococcus ruber IEGM 231 was found to
      stimulate tumor necrosis factor-alpha (TNF-alpha), interleukin (IL) -1beta and IL
      6 production when applied as an ultrasonic emulsion to the adherent human
      peripheral blood monocyte culture. However, a lack of cytokine-stimulating
      activity was registered with the GLB applied as a hydrophobic film coating in 24
      well culture plates, indicating that it may have been due to its inhibitory
      effect on monocyte adhesion. The mode of GLB application may therefore play an
      important role in in vitro assay of immunostimulatory activity of this compound
      as well as other bacterial glycolipids. Additionally, GLB from R. ruber displayed
      no cytotoxicity against human lymphocytes and therefore could be proposed as a
      potential immunomodulating and antitumor agent.

PMID- 21858500
TI  - Importance of the temporal structure of movement sequences on the ability of
      monkeys to use serial order information.
AB  - The capacity to acquire motor skills through repeated practice of a sequence of
      movements underlies many everyday activities. Extensive research in humans has
      dealt with the importance of spatial and temporal factors on motor sequence
      learning, standing in contrast to the few studies available in animals,
      particularly in nonhuman primates. In the present experiments, we studied the
      effect of the serial order of stimuli and associated movements in macaque monkeys
      overtrained to make arm-reaching movements in response to spatially distinct
      visual targets. Under different conditions, the temporal structure of the motor
      sequence was varied by changing the duration of the interval between successive
      target stimuli or by adding a cue that reliably signaled the onset time of the
      forthcoming target stimulus. In each condition, the extent to which the monkeys
      are sensitive to the spatial regularities was assessed by comparing performance
      when stimulus locations follow a repeating sequence, as opposed to a random
      sequence. We observed no improvement in task performance on repeated sequence
      blocks, compared to random sequence blocks, when target stimuli are relatively
      distant from each other in time. On the other hand, the shortening of the time
      interval between successive target stimuli or, more efficiently, the addition of
      a temporal cue before the target stimulus yielded a performance advantage under
      repeated sequence, reflected in a decrease in the latency of arm and saccadic eye
      movements accompanied by an increased tendency for eye movements to occur in an
      anticipatory manner. Contrary to the effects on movement initiation, the serial
      order of stimuli and movements did not markedly affect the execution of movement.
      Moreover, the location of a given target in the random sequence influenced task
      performance based on the location of the preceding target, monkeys being faster
      in responding as a result of familiarity caused by extensive practice with some
      target transitions also used in the repeated sequence. This performance advantage
      was most prominently detectable when temporal prediction of forthcoming target
      stimuli was optimized. Taken together, the present findings demonstrate that the
      monkey's capacity to make use of serial order information to speed task
      performance was dependent on the temporal structure of the motor sequence.

PMID- 21858501
TI  - Timing movements to interval durations specified by discrete or continuous
      sounds.
AB  - Understanding how the timing of motor output is coupled to sensory temporal
      information is largely based on synchronisation of movements through small motion
      gaps (finger taps) to mostly empty sensory intervals (discrete beats). This study
      investigated synchronisation of movements between target barriers over larger
      motion gaps when closing time gaps of intervals were presented as either
      continuous, dynamic sounds, or discrete beats. Results showed that although
      synchronisation errors were smaller for discrete sounds, the variability of
      errors was lower for continuous sounds. Furthermore, finger movement between
      targets was found to be more sinusoidal when continuous sensory information was
      presented during intervals compared to discrete. When movements were made over
      larger amplitudes, synchronisation errors tended to be more positive and
      movements between barriers more sinusoidal, than for movements over shorter
      amplitudes. These results show that the temporal control of movement is not
      independent from the form of the sensory information that specifies time gaps or
      the magnitude of the movement required for synchronisation.

PMID- 21858502
TI  - Food's visually perceived fat content affects discrimination speed in an
      orthogonal spatial task.
AB  - Choosing what to eat is a complex activity for humans. Determining a food's
      pleasantness requires us to combine information about what is available at a
      given time with knowledge of the food's palatability, texture, fat content, and
      other nutritional information. It has been suggested that humans may have an
      implicit knowledge of a food's fat content based on its appearance; Toepel et al.
      (Neuroimage 44:967-974, 2009) reported visual-evoked potential modulations after
      participants viewed images of high-energy, high-fat food (HF), as compared to
      viewing low-fat food (LF). In the present study, we investigated whether there
      are any immediate behavioural consequences of these modulations for human
      performance. HF, LF, or non-food (NF) images were used to exogenously direct
      participants' attention to either the left or the right. Next, participants made
      speeded elevation discrimination responses (up vs. down) to visual targets
      presented either above or below the midline (and at one of three stimulus onset
      asynchronies: 150, 300, or 450 ms). Participants responded significantly more
      rapidly following the presentation of a HF image than following the presentation
      of either LF or NF images, despite the fact that the identity of the images was
      entirely task-irrelevant. Similar results were found when comparing response
      speeds following images of high-carbohydrate (HC) food items to low-carbohydrate
      (LC) food items. These results support the view that people rapidly process (i.e.
      within a few hundred milliseconds) the fat/carbohydrate/energy value or, perhaps
      more generally, the pleasantness of food. Potentially as a result of HF/HC food
      items being more pleasant and thus having a higher incentive value, it seems as
      though seeing these foods results in a response readiness, or an overall alerting
      effect, in the human brain.

PMID- 21858503
TI  - Arthroplasty versus arthrodesis for end-stage ankle arthritis: decision analysis
      using Markov model.
AB  - BACKGROUND: Total ankle arthroplasty and arthrodesis are the two mainstreams of
      treatment for end-stage ankle arthritis. This study was performed to determine
      which is a better choice for ankle arthritis, using a decision analysis and
      Markov model to reflect the repetitive nature of revision arthroplasty. METHODS:
      Based on current published evidence, a decision tree was constructed to compare
      the clinical outcomes of total ankle arthroplasty and arthrodesis, which
      contained the possible clinical events and the probabilities. Total ankle
      arthroplasty was subject to revision arthroplasty, and a Markov model was adopted
      for this branch to reflect this repetitive trait of the procedure. Arthrodesis
      could cause adjacent arthritis, and a conventional decision analysis model was
      adopted for this branch. Quality well-being index score was used for clinical
      outcome assessment, which was the utility in the decision tree. Sensitivity
      analysis was performed to test the stability of the decision tree and the
      threshold values. RESULTS: The model favoured total ankle arthroplasty over
      arthrodesis in terms of quality well-being index score. Sensitivity analysis
      showed that the model was considerably stable, unaffected by the changes in
      probabilities of failure after total ankle arthroplasty and adjacent arthritis
      after arthrodesis. CONCLUSIONS: Based on current evidence, total ankle
      arthroplasty was found to be a better treatment than arthrodesis for ankle
      arthritis. Future development in the implant materials, improved understanding of
      ankle biomechanics, and surgical techniques will further enhance the clinical
      outcome of total ankle arthroplasty.

PMID- 21858505
TI  - The ornament-condition relationship varies with parasite abundance at population
      level in a female bird.
AB  - Environmental heterogeneity is expected to create variation in the ornament
      condition relationship. This topic has been studied in males with less attention
      being given to females. Here, we explore inter-population variation in the
      relationship between the size of a male-like trait, supra-orbital combs, and body
      mass in female red grouse Lagopus lagopus scoticus. We used the abundance of the
      nematode Trichostrongylus tenuis, a parasite with strong negative effects on this
      species, as a proxy of environmental conditions. We studied six populations over
      5 years and showed that the comb size-body mass relationship varied with mean
      parasite abundance, with stronger ornament-condition relationships in populations
      with higher parasite infection levels. Our study supports the idea that
      environmental conditions, and in particular parasite infection levels, may affect
      the reliability of female ornaments as condition indicators.

PMID- 21858504
TI  - No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood
      with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity
      Study in the Young (DAISY).
AB  - AIMS/HYPOTHESIS: The aim of the study was to investigate the association between
      vitamin D intake and status and the risk of islet autoimmunity (IA) and
      subsequent type 1 diabetes in children at increased risk of type 1 diabetes.
      METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) in Denver, CO, USA,
      has been following children at increased risk of diabetes since 1993. As of
      February 2011, 198 children developed IA during follow-up of 2,644 DAISY
      children. Vitamin D intake and plasma 25-hydroxyvitamin D [25(OH)D] were measured
      longitudinally. Proportional hazards regression analyses of time to IA, or type 1
      diabetes in IA-positive children, were conducted, with vitamin D intake and
      25(OH)D as time-varying covariates. HRs were calculated for a standard deviation
      difference in exposure, with adjustment for confounders. RESULTS: Intake of
      vitamin D was not associated with the risk of IA (adjusted HR 1.13; 95% CI 0.95,
      1.35; p = 0.18) nor progression to diabetes in IA-positive children (adjusted HR
      1.30; 95% CI 0.91, 1.86; p = 0.15). Moreover, 25(OH)D level was not associated
      with the risk of IA (adjusted HR 1.12; 95% CI 0.88, 1.43; p = 0.36), nor
      progression to diabetes in IA-positive children (adjusted HR 0.91; 95% CI 0.68,
      1.22; p = 0.54). In the 128 children in whom we measured 25(OH)D at 9 months of
      age, 25(OH)D was not associated with risk of IA (n = 30 IA-positive children)
      (adjusted HR 1.02; 95% CI 0.96, 1.07; p = 0.58). CONCLUSIONS/INTERPRETATION:
      Neither vitamin D intake nor 25(OH)D levels throughout childhood were associated
      with the risk of IA or progression to type 1 diabetes in our population.

PMID- 21858506
TI  - Merkel cell carcinoma: a population-based study on mortality and the association
      with other cancers.
AB  - BACKGROUND: Few population-based epidemiological data are available on Merkel
      cell carcinoma (MCC), a rare lethal non-melanoma skin cancer. We analysed
      multiple-cause-of-death records to describe MCC mortality and trends and the
      association with other primary cancers. METHODS: We reviewed all 6,713,059 death
      certificates in Italy (1995-2006) to identify those mentioning MCC. We evaluated
      the association with other primary cancers by calculating the ratio of observed
      to expected deaths, using a standardized mortality ratio (SMR)-like analysis. We
      also evaluated the geographic distribution of deaths. RESULTS: We identified 351
      death certificates with the mention of MCC. The age-adjusted mortality was
      0.031/100,000, with a significant trend of increase and a slight north-south
      gradient. There was a significant deficit for solid cancers (SMR = 0.15) and a
      non-significant excess for lymphohematopoietic malignancies (SMR = 1.62). There
      were significant excesses for chronic lymphocytic leukemia (SMR = 4.07) and
      Waldenstrom's macroglobulinemia (SMR = 27.2) and a non-significant excess for
      chronic myeloid leukemia (SMR = 5.12). CONCLUSIONS: The increase in MCC mortality
      reflects the incidence trend in the literature. The association with chronic
      lymphocytic leukemia confirms the importance of immunologic factors in MCC.
      Regarding Waldenstrom's macroglobulinemia, an association with MCC has never been
      reported.

PMID- 21858508
TI  - The benefit of ultrasound biomicroscopy (UBM) in management of total Descemet's
      membrane detachment after deep sclerectomy surgery.
AB  - The purpose of this study is to report the importance of ultrasound biomicroscopy
      (UBM) in the diagnosis of Descemet's membrane detachment (DMD) and the efficacy
      of sulfur hexafluoride (SF6) gas in its management. DMD was identified by UBM in
      a 22-year-old woman with juvenile glaucoma who underwent deep sclerectomy surgery
      and developed severe corneal oedema postoperatively. SF6 gas 15% was injected
      into the anterior chamber. The procedure resulted in reattachment of Descemet's
      membrane and a completely clear cornea. DMD can be easily overlooked or
      misdiagnosed after non-penetrating glaucoma surgery. UBM is helpful in diagnosis
      and management of DMD and descemetopexy with SF6 gas can give good results.

PMID- 21858507
TI  - Mechanical loading: bone remodeling and cartilage maintenance.
AB  - Bone remodeling and cartilage maintenance are strongly influenced by
      biomechanical signals generated by mechanical loading. Although moderate loading
      is required to maintain bone mass and cartilage homeostasis, loading can cause
      deleterious effects such as bone fracture and cartilage degradation. Because a
      tight coupling exists between cartilage and bone, alterations in one tissue can
      affect the other. Bone marrow lesions are often associated with an increased risk
      of developing cartilage defects, and changes in the articular cartilage integrity
      are linked to remodeling responses in the underlying bone. Although mechanisms
      regulating the maintenance of these two tissues are different, compelling
      evidence indicates that the signal pathways crosstalk, particularly with the Wnt
      pathway. A better understanding of the complex tempero-spatial interplay between
      bone remodeling and cartilage degeneration will help develop a therapeutic
      loading strategy that prevents bone loss and cartilage degeneration.

PMID- 21858509
TI  - The role of temporal properties on the detection of temporal violations: insights
      from pupillometry.
AB  - Scripts store the temporal order of component events of everyday activities as
      well as the temporal position of the events within the activity (early or late).
      When confronted with an activity, predictions are generated about how the
      component events will unfold. Thereby, an error-detection mechanism continuously
      monitors whether they unfold as anticipated or not in order to reveal errors in
      the unfolding activity. We investigated whether the temporal position "early" or
      "late" influenced the detection of errors using the pupillary response as an
      index of cognitive resource consumption. An event triplet consisting of three
      events was presented in a chronological or non-chronological temporal order.
      Crucially, the triplet focused either on the beginning (temporal position
      "early") or the end (temporal position "late") of an activity. We assumed that
      these position codes would be used to facilitate error detection when a non
      chronological event was presented. Results showed that errors in the temporal
      order were detected more successfully in early than in late triplets. Results
      further suggest that strong predictions are formed about how an activity begins.
      Violations of this prediction must be overcome by zooming into the representation
      and allocating attention to the temporal position that consumes cognitive
      resources. Only after zooming in has taken place successfully may the position
      codes be used to anticipate temporal violations in unfolding event sequences.

PMID- 21858510
TI  - Usefulness of a dual-input single-compartment model for quantitative evaluation
      of thioacetamide-induced acute liver injury in rats using dynamic contrast
      enhanced computed tomography.
AB  - We undertook this study to investigate the usefulness of a dual-input single
      compartment model for evaluating thioacetamide (TAA)-induced acute liver injury
      in rats by use of dynamic contrast-enhanced computed tomography (DCE-CT). The
      rats in the TAA-treated group were injected intravenously with 140 mg/kg (n = 10)
      or 280 mg/kg (n = 10) of TAA, whereas those in the control group (n = 10) were
      injected with saline. The rate constants for the transfer of the contrast agent
      from the hepatic artery to the liver (K(1a)), from the portal vein to the liver
      (K(1p)), and from the liver to the blood (k2), as well as liver perfusion (LP),
      the arterial fraction of LP (AFLP), distribution volume (DV), and mean transmit
      time (MTT) were estimated with use of the dual-input single-compartment model.
      Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were
      also measured. K(1p), k2, and LP decreased significantly in the TAA-treated group
      compared to those in the control group, whereas K(1a), AFLP, DV, and MTT
      increased significantly. The above parameters except for K (1a) were
      significantly correlated with both AST and ALT. We concluded that DCE-CT using
      the dual-input single-compartment model is useful for quantitative evaluation of
      TAA-induced acute liver injury.

PMID- 21858511
TI  - Effects of lead on the growth, lead accumulation and physiological responses of
      Pluchea sagittalis.
AB  - This work aimed to study the process of stress adaptation in root and leaves of
      different developmental stages (apex, middle and basal regions) of Pluchea
      sagittalis (Lam.) Cabrera plants grown under exposure to five Pb levels (0, 200,
      400, 600 and 1000 MUM) for 30 days. Pb concentration and content in roots, stems,
      and leaves of different developmental stages increased with external Pb level.
      Consumption of nutrient solution, transpiration ratio, leaf fresh weight, leaf
      area, and shoot length decreased upon addition of Pb treatments. However, dry
      weight of shoot parts and roots did not decrease upon addition of Pb treatments.
      Based on index of tolerance, the roots were much more tolerant to Pb than shoots.
      delta-aminolevulinic acid dehydratase activity was decreased by Pb treatments,
      whereas carotenoid and chlorophyll concentrations were not affected. Lipid
      peroxidation and hydrogen peroxide concentration both in roots and leaves
      increased with increasing Pb levels. Pb treatments increased ascorbate peroxidase
      activity in all plant parts, while superoxide dismutase activity increased in
      leaves and did not change in roots. Catalase activity in leaves from the apex
      shoot was not affected by Pb, but in other plant parts it was increased. Pb
      toxicity caused increase in non-protein thiol groups concentration in shoot
      parts, whereas no significant difference was observed in roots. Both root and
      shoot ascorbic acid concentration increased with increasing Pb level. Therefore,
      it seems that Pb stress triggered an efficient defense mechanism against
      oxidative stress in P. sagittalis but its magnitude was depending on the plant
      organ and of their physiological status. In addition, these results suggest that
      P. sagittalis is Pb-tolerant. In conclusion, P. sagittalis is able to accumulate
      on average 6730 and 550 MUg Pb g(-1) dry weight, respectively, in the roots and
      shoot, a physiological trait which may be exploited for the phytoremediation of
      contaminated soils and waters.

PMID- 21858512
TI  - Uptake pathways and subcellular fractionation of Cd in the polychaete Nereis
      diversicolor.
AB  - Polychaetes have often been utilized as indicator species to investigate the
      impacts of pollutants, such as heavy metals. The uptake of Cd by the polychaete
      Nereis diversicolor was determined at varying Ca concentrations and with pre
      exposure to Ca ion channel blockers and metabolic inhibitors in simulated sea
      water over 1 week period. The supply of Ca in simulated sea water inhibited Cd
      uptake and increased Ca concentration in N. diversicolor after 10 MUM Cd
      exposure. Pre-exposure to a Ca-channel blocker (Lanthanum) significantly
      inhibited Cd uptake, suggesting that the uptake of Cd was exerted at a Ca
      channel. N-ethylmaleimide, which specifically binds to sulfhydryl groups,
      inhibited Cd uptake at 10 MUM, implying that the transport of Cd is carrier
      mediated by proteins or other SH-containing compounds. Subcellular Cd
      distribution analysis showed that more than 60% of the total Cd associated with
      the cytosolic fraction. The presence of higher concentration of Ca in simulated
      sea water did not impact the proportional subcellular distribution of Cd in N.
      diversicolor. Nevertheless, the supply of Ca could significantly lower Cd
      concentration in cytosol and cellular debris. The present study provides evidence
      that Cd transport by N. diversicolor was mediated mainly through lanthanum-
      sensitive Ca ion channels and accumulated by SH-containing compounds. These
      results help to understand the uptake mechanism and subcellular distribution of
      Cd in polychaetes.

PMID- 21858513
TI  - Spatial gradients of methylmercury for breeding common loons in the Laurentian
      Great Lakes region.
AB  - Much of the Laurentian Great Lakes region is a mercury-sensitive landscape, in
      which atmospheric deposition and waterborne sources of mercury (Hg) have led to
      high concentrations of bioavailable methylmercury (MeHg) in predatory fish and
      piscivorous wildlife. Efforts since the early 1990s have established the common
      loon (Gavia immer) as the primary avian indicator for evaluating the exposure and
      effects of MeHg in North America. A regional Hg dataset was compiled from
      multiple loon tissue types and yellow perch (Perca flavescens), a preferred prey
      fish species for loons. Hg exposure in loons and perch was modeled to develop
      male and female loon units (MLU and FLU, respectively), standardized metrics that
      represent the estimated blood Hg exposure of a male or female loon for a given
      loon territory or water body. Using this common endpoint approach to assess loon
      Hg exposure, the authors demonstrate spatial trends in biotic Hg concentrations,
      examine MeHg availability in aquatic ecosystems of the Great Lakes region in
      relation to landscape-level characteristics, and identify areas with potentially
      significant adverse reproductive impacts to loons and other avian piscivores.
      Based on 8,101 MLUs, seven biological Hg hotspots were identified in the Great
      Lakes region. Policy-relevant applications are presented.

PMID- 21858514
TI  - Evaluating chromosomal damage in workers exposed to hexavalent chromium and the
      modulating role of polymorphisms of DNA repair genes.
AB  - PURPOSE: Welders have been chronically exposed to hexavalent chromium with
      potential consequences on chromosomal integrity. Our study is focused on the
      extent of any such chromosomal aberrations with respect to chromium levels in the
      blood of welders as well as on the tentative modulating role of polymorphisms in
      DNA repair genes XPD Lys751Gln, XPG Asn114His, XPC Lys939Gln, hOGG1 Ser326Cys and
      XRCC1 Arg399Gln on chromosomal damage. METHODS: The study was conducted on 144
      individuals consisting of 73 welders exposed to chromium for 10.2 +/- 1.67 years
      and 71 control individuals without known exposures. Chromosomal aberrations,
      their chromatid-type and chromosome-type aberrations were detected by
      conventional cytogenetic analysis. XPD, XPG, XPC, hOGG1 and XRCC1 gene
      polymorphisms were assayed for by Taqman SNP genotyping assay ("Assay-by-Demand")
      using Real-Time allelic discrimination on AB 7500 equipment. Chromium
      concentration in the blood was determined by atomic absorption spectrophotometry.
      RESULTS: The level of chromium in the blood of welders ranged between 0.032 and
      0.182 MUmol l(-1) and was significantly higher than that in controls (0.07 +/-
      0.04 MUmol l(-1) vs. 0.03 +/- 0.007 MUmol l(-1)). Parameters of chromosomal
      damage were similar in both the exposed and the control individuals (1.89% vs.
      1.70% for total chromosomal aberrations, 0.97% vs. 0.88% for chromosome-type and
      0.92% vs. 0.80% for chromatid-type, respectively). Chromatid-type of aberrations
      positively correlated with the level of chromium in the blood (r = 0.28; P =
      0.02). Significantly higher total chromosomal aberrations were detected in
      individuals with homozygous variant polymorphism in XRCC1 Arg399Gln gene as
      compared to those with heterozygous and homozygous wild-type genotypes (2.20,
      1.89 and 1.48%, respectively; P = 0.01). A similar tendency was found for
      chromatid-type aberrations (1.30% for homozygous variant genotype bearers, 0.94%
      for those with heterozygous genotype and 0.75% for carriers of homozygous wild
      type genotype, respectively; P = 0.04). CONCLUSIONS: Although no apparent
      increase in chromosomal damage was recorded in chromium-exposed welders in
      comparison with controls, genetic make-up in DNA repair genes may increase
      susceptibility toward adverse effect of chromium.

PMID- 21858515
TI  - The complexity of personality: advantages of a genetically sensitive multi-group
      design.
AB  - Findings from many behavioral genetic studies utilizing the classical twin design
      suggest that genetic and non-shared environmental effects play a significant role
      in human personality traits. This study focuses on the methodological advantages
      of extending the sampling frame to include multiple dyads of relatives. We
      investigated the sensitivity of heritability estimates to the inclusion of
      sibling pairs, mother-child pairs and grandparent-grandchild pairs from the
      German Socio-Economic Panel Study in addition to a classical German twin sample
      consisting of monozygotic- and dizygotic twins. The resulting dataset contained
      1.308 pairs, including 202 monozygotic and 147 dizygotic twin pairs, along with
      419 sibling pairs, 438 mother-child dyads, and 102 grandparent-child dyads. This
      genetically sensitive multi-group design allowed the simultaneous testing of
      additive and non-additive genetic, common and specific environmental effects,
      including cultural transmission and twin-specific environmental influences. Using
      manifest and latent modeling of phenotypes (i.e., controlling for measurement
      error), we compare results from the extended sample with those from the twin
      sample alone and discuss implications for future research.

PMID- 21858516
TI  - Thyroid cancer after Chernobyl: mechanisms of overestimation.

PMID- 21858517
TI  - [Temporal bone surgery. Surgical sequelae and complications].
AB  - The saying "no surgery, no surgical complications" is certainly true for all
      specialties. Three categories of undesired events may occur following surgery:
      surgical sequelae, failure to cure and complications. A critical self-analysis of
      surgical complications often reveals that these arise in vexing fashion according
      to Murphy's law, i.e. "what can go wrong, will go wrong". Incomplete preoperative
      evaluation, insufficient exposure of the surgical field, failure to identify
      surgical landmarks and misjudgment of the patient's preoperative complaints may
      culminate in an undesired surgical outcome. Modern preoperative radiology, the
      possibilities of actual or even virtual temporal bone drilling in the laboratory
      and the surgeon's level of experience all ensure the relative rarity of relevant
      surgical complications in otology.

PMID- 21858518
TI  - Is adrenal ovarian thecal metaplasia a misnomer? Report of three cases of radial
      scar-like spindle cell myofibroblastic nodule of the adrenal gland.
AB  - Ovarian thecal metaplasia is a rare tumor-like mesenchymal lesion of the adrenal
      gland that has been reported mainly in postmenopausal women and rarely in men. It
      was originally described as a wedge-shaped lesion composed of ovarian-like stroma
      resembling theca that shows continuity with the capsule of the adrenal gland. We
      report three cases and identify that these lesions can resemble a radial scar.
      While a single case has been reported to contain true ovarian stromal elements,
      there was no evidence of steroidogenic differentiation in our cases. These
      findings justify the need for a better terminology since the entity falls within
      the spectrum of fibroblastic-myofibroblastic proliferations. We propose the
      terminology of "radial scar-like spindle cell myofibroblastic nodule of the
      adrenal gland" as a more accurate nomenclature to designate these lesions.
      Although rare, calcifying fibrous tumor of the adrenal gland, hypertrophic nerve
      bundles, and peripheral nerve sheath tumors may mimic these lesions.

PMID- 21858519
TI  - Disseminated cutaneous mucormycosis in a patient on high-dose steroid therapy for
      severe ARDS.

PMID- 21858520
TI  - Increasing consumption of MRSA-active drugs without increasing MRSA in German
      ICUs.
AB  - PURPOSE: The aim of our study was to analyze changes in the consumption of MRSA
      active antibiotics and in the burden of methicillin-resistant S. aureus (MRSA)
      over a period of 9 years in a network of German intensive care units (ICU).
      METHODS: Data from 55 ICUs in Germany were analyzed from 2001 through 2009. The
      term "old MRSA-active antibiotics" included vancomycin, teicoplanin and
      fosfomycin, whereas the term "new MRSA-active antibiotics" included
      quinupristin/dalfopristin, linezolid and daptomycin. The burden of MRSA was
      defined as MRSA per 1,000 patient-days. RESULTS: A total of 1,584,995 patient
      days and 32,450 S. aureus isolates were analyzed. The burden of MRSA was 4.4, and
      the pooled mean MRSA resistance proportion was 21.8%. Both parameters did not
      change significantly over time. In contrast, MRSA-active antibiotics more than
      doubled from 44 defined daily doses per 1,000 patient-days in 2001 to 92 in 2009.
      This was due to the significant increase of new MRSA-active antibiotics (from 1
      to 40), whereas old MRSA antibiotics stayed stable (43 in 2001 and 52 in 2009).
      CONCLUSION: New MRSA-active antibiotics did not replace old ones, but were added
      on top. The use of new MRSA-active antibiotics-mainly linezolid-steadily
      increased over a period of 9 years, although the burden of MRSA stayed stable, as
      did the proportion of MRSA (%).

PMID- 21858521
TI  - Recruitment by sustained inflation: time for a change.

PMID- 21858522
TI  - Optimal duration of a sustained inflation recruitment maneuver in ARDS patients.
AB  - PURPOSE: To measure the dynamics of recruitment and the hemodynamic status during
      a sustained inflation recruitment maneuver (RM) in order to determine the optimal
      duration of RM in acute respiratory distress syndrome (ARDS) patients. METHODS:
      This prospective study was conducted in a 12-bed intensive care unit (ICU) in a
      general hospital. A 40 cmH(2)O sustained inflation RM maintained for 30 s was
      performed in 50 sedated ventilated patients within the first 24 h of meeting ARDS
      criteria. Invasive arterial pressures, heart rate, and SpO(2) were measured at 10
      s intervals during the RM. The volume increase during the RM was measured by
      integration of the flow required to maintain the pressure at 40 cmH(2)O, which
      provides an estimation of the volume recruited during the RM. Raw data were
      corrected for gas consumption and fitted with an exponential curve in order to
      determine an individual time constant for the volume increase. RESULTS: The
      average volume increase and time constant were 210 +/- 198 mL and 2.3 +/- 1.3 s,
      respectively. Heart rate, diastolic arterial pressure, and SpO(2) did not change
      during or after the RM. Systolic and mean arterial pressures were maintained at
      10 s, decreased significantly at 20 and 30 s during the RM, and recovered to the
      pre-RM value 30 s after the end of the RM (ANOVA, p < 0.01). CONCLUSIONS: In
      early-onset ARDS patients, most of the recruitment occurs during the first 10 s
      of a sustained inflation RM. However, hemodynamic impairment is significant after
      the tenth second of RM.

PMID- 21858524
TI  - [Perspectives of corneal transplantation. New surgical and transplantation
      techniques].

PMID- 21858523
TI  - [Corneal cross-linking with hypo-osmolar riboflavin solution for keratoconus with
      thin corneas].
AB  - BACKGROUND: The aim of this study was to evaluate the 1-year results of 32
      keratoconic eyes with thin corneas which were treated by hypo-osmolar riboflavin
      solution and ultraviolet A (UVA) collagen cross-linking (CXL). PATIENTS AND
      METHODS: Patients with progressive keratoconus and a corneal thickness (CT) less
      than 400 um (without epithelium) were included in this study. The CT was measured
      with an ultrasound device (Tomey SP-3000, Nishi-ku, Nagoya, Japan). An increase
      in the maximum topographic K-value at the apex of keratoconus and a reduction in
      corneal thickness with or without changes in visual acuity (VA) within the last
      year were considered to be progression. A total of 32 eyes with an additional
      follow-up within 1 year were evaluated before and after the procedure.
      Examinations consisted of an evaluation of VA, corneal topography, slit-lamp
      microscopy and corneal thickness measurements. RESULTS: Preoperatively the mean
      corneal thickness (with epithelium) was 382.3+/-41.9 MUm and after removal of the
      epithelium the thickness of the cornea was reduced to 337.0+/-51.9 MUm. After the
      application of hypo-osmolar riboflavin solution the mean value increased to
      451.8+/-46.7 MUm. Preoperatively the mean K-value of the apex of the keratoconus
      was 65.6+/-11.2 dopters, and 1 year after treatment this value remained
      relatively unchanged at 64.9+/-11.0 diopters (P=0.839). Mean VA at the time of
      the treatment was 0.63+/-0.37 logMAR and 1 year after the treatment this value
      was not statistically different (0.59+/-0.42 logMAR; P=0.662). In the last follow
      up examination 1 year after the procedure all corneas were transparent without
      any scarring lesions in the stroma. CONCLUSIONS: The results of this study using
      hypo-osmolar riboflavin solution in a cross-linking procedure for thin corneas
      showed a stability of keratoconus 1 year after CXL. Application of the hypo
      osmolar riboflavin solution prevented cross-linked corneas from developing
      stromal scars.

PMID- 21858525
TI  - Specificity of carboxypeptidases from Actinomucor elegans and their debittering
      effect on soybean protein hydrolysates.
AB  - The specificities of carboxypeptidases from Actinomucor elegans were investigated
      by determining enzymatic activities at pH 7.0 and pH 4.0 with 16 Z-dipeptides and
      three Z-tripeptides as substrates. The debittering effect was evaluated and the
      free amino acid compositions of the soybean protein hydrolysates were analyzed
      before and after treatment with A. elegans extract at pH 7.0 and pH 4.0, with
      carboxypeptidases from Aspergillus oryzae as control. The results of the enzyme
      activity determinations indicated that carboxypeptidases from A. elegans prefer
      hydrophobic substrates, such as Z-Phe-Leu, Z-Phe-Tyr-Leu, and Z-Phe-Tyr. The
      sensory evaluation and free amino acid composition analysis showed that these
      carboxypeptidases are efficient tools for decreasing the bitterness of peptides
      because they liberated the fewest free amino acids, which consisted of 73%
      hydrophobic amino acids, under acidic conditions. Carboxypeptidases from A.
      elegans display promising prospects for future applications in the protein
      hydrolysate industry.

PMID- 21858526
TI  - Lessons learned from a HDR brachytherapy well ionisation chamber calibration
      error.
AB  - The outcomes of a recent brachytherapy well-type ionization chamber calibration
      error are given in the hope that other brachytherapy treatment centres may better
      understand the importance of each entry stated in a well chamber calibration
      certificate. A Nucletron Source Dosimetry System (SDS) PTW well-type ionization
      chamber was sent for a biennial calibration in September 2010. Upon calibration
      of the chamber, it was discovered that the previous calibration (in July 2008)
      contained a +2.6% error in the chamber calibration coefficient. Investigation of
      the information on the 2008 well chamber calibration certificate indicated the
      source of the error, which could or should have been detected by both the
      calibration laboratory and/or the radiation therapy department upon return of the
      chamber. Consideration must be given to all values and conditions given on the
      calibration certificate when accepting a ionization chamber back from a
      calibration laboratory. The issue of whether the source strength from the source
      calibration certificate or the measured source strength from the calibrated
      ionization chamber should be entered into the treatment unit is also raised.

PMID- 21858527
TI  - Pretargeted radioimmunotherapy of colorectal cancer metastases: models and
      pharmacokinetics predict influence of the physical and radiochemical properties
      of the radionuclide.
AB  - PURPOSE: We investigated influences of pretargeting variables, tumor location,
      and radionuclides in pretargeted radioimmunotherapy (PRIT) as well as estimated
      tumor absorbed doses. METHODS: LS-174T human colonic carcinoma cells expressing
      carcinoembryonic antigen (CEA) were inoculated in nude mice. Biodistribution of a
      bispecific anti-CEA x anti-hapten antibody, TF2, and of a TF2-pretargeted peptide
      was assessed and a multi-compartment pharmacokinetic model was devised. Tissue
      absorbed doses were calculated for (131)I, (177)Lu, (90)Y, (211)At, and (213)Bi
      using realistic specific activities. RESULTS: Under conditions optimized for
      tumor imaging (10:1 TF2 to peptide molar ratio, interval time 15-24 h), tumor
      uptake reached ~9 ID/g in subcutaneous tumors at 2 h with very low accretion in
      normal tissues (tumor to blood ratio >20:1 after 2 h). For a low dose of peptide
      (0.04 nmol), (211)At is predicted to deliver a high absorbed dose to tumors [41.5
      Gy considering a relative biologic effect (RBE) of 5], kidneys being dose
      limiting. (90)Y and (213)Bi would also deliver high absorbed doses to tumor (18.6
      for (90)Y and 26.5 Gy for (213)Bi, taking RBE into account, for 0.1 nmol) and
      acceptable absorbed doses to kidneys. With hepatic metastases, a twofold higher
      tumor absorbed dose is expected. Owing to the low activities measured in blood,
      the bone marrow absorbed dose is expected to be without significant toxicity.
      CONCLUSION: Pretargeting achieves high tumor uptake and higher tumor to
      background ratios compared to direct RIT. Short-lived radionuclides are predicted
      to deliver high tumor absorbed doses especially (211)At, with kidneys being the
      dose-limiting organ. (177)Lu and (131)I should be considered for repeated
      injections.

PMID- 21858529
TI  - Congratulations, Rudiger von Kummer!

PMID- 21858528
TI  - Impact of [18F]FDG PET imaging parameters on automatic tumour delineation: need
      for improved tumour delineation methodology.
AB  - PURPOSE: Delineation of tumour boundaries is important for quantification of
      [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies
      and for definition of biological target volumes in radiotherapy. Several (semi
      )automatic tumour delineation methods have been proposed, but these methods
      differ substantially in estimating tumour volume and their performance may be
      affected by imaging parameters. The main purpose of this study was to explore the
      performance dependence of various (semi-)automatic tumour delineation methods on
      different imaging parameters, i.e. reconstruction parameters, noise levels and
      tumour characteristics, and thereby the need for standardization or inter
      institute calibration. METHODS: Six different types of delineation methods were
      evaluated by assessing accuracy and precision in estimating tumour volume from
      simulations and phantom experiments. The evaluated conditions were various tumour
      sizes, iterative reconstruction algorithm settings and image filtering, tumour to
      background ratios (TBR), noise levels and region growing initializations.
      RESULTS: The accuracy of all automatic delineation methods was influenced when
      imaging parameters were varied. The performance of all tumour delineation methods
      depends on variation of TBR, image resolution and image noise level, and to a
      lesser extent on number of iterations during image reconstruction or the
      initialization method of the region generation. For sphere sizes larger than 20
      mm diameter a contrast-oriented method provided the most accurate results, on
      average, over all simulated conditions. For threshold-based methods the accuracy
      of tumour delineation improved after image denoising/filtering. CONCLUSION: The
      accuracy and precision of all studied tumour delineation methods was affected by
      physiological and imaging parameters. The latter illustrates the need for
      optimizing imaging parameters and/or for careful calibration and optimization of
      delineation methods.

PMID- 21858531
TI  - Labs in the field? Rocky mountain biological stations in the early twentieth
      century.
AB  - Biological field stations proliferated in the Rocky Mountains region of the
      western United States during the early decades of the twentieth century. This
      essay examines these Rocky Mountain field stations as hybrid lab-field sites from
      the perspective of the field side of the dichotomy: as field sites with raised
      walls rather than as laboratories whose walls with the natural world have been
      lowered. Not only were these field stations transformed to be more like
      laboratories, but they were also embedded within the particular regional
      environmental and institutional context of the Rocky Mountains. Using the
      University of Colorado's Mountain Laboratory at Tolland and other contemporaneous
      sites as examples, this essay analyzes key features of these sites, including
      their location within transportation networks, buildings, equipment, personnel,
      scheduling, recreational and social activities, and other material and social
      practices on the ground. Considering both the distinctive and shared
      characteristics of the Rocky Mountain field stations in comparison to other types
      of field stations provides a more complete picture of the diversity and range of
      lab-field hybrid sites in the biological sciences in the early twentieth-century
      United States.

PMID- 21858532
TI  - Docetaxel plus gemcitabine in combination with capecitabine as treatment for
      inoperable pancreatic cancer: a phase II study.
AB  - PURPOSE: To evaluate the activity and tolerance of gemcitabine in combination
      with docetaxel and capecitabine in previously untreated patients with advanced
      pancreatic cancer. PATIENTS AND METHODS: Chemotherapy-naive patients with locally
      advanced or metastatic pancreatic cancer were treated with gemcitabine (1,500
      mg/m(2) on days 1 and 15), docetaxel (50 mg/m(2) on days 1 and 15) and
      capecitabine (2,250 mg/m(2), orally in two daily divided doses, on days 1-7 and
      15-21). All three drugs were administered in 4-week cycles, in an initial
      prospective plan of six cycles. The primary end-point was response rate. RESULTS:
      Forty patients were enrolled in the study. At the time of enrollment, 40% of
      patients had locally advanced and 60% metastatic disease. All patients were
      evaluable for response and toxicity. On an intent-to-treat analysis, the overall
      response and disease control rates were 40 and 80%, respectively. The median
      progression-free survival was 6.0 months, and the median overall survival was 9.0
      months. Major grade 3/4 toxicities were neutropenia (17.5%), diarrhea (10%) and
      hand-foot syndrome (7.5%). There was no treatment-related death. CONCLUSION: The
      combination of gemcitabine with docetaxel and capecitabine is feasible and
      exhibits satisfactory degree of activity in patients with advanced pancreatic
      cancer, deserving further exploration.

PMID- 21858533
TI  - Immunological responses in cancer patients after vaccination with the therapeutic
      telomerase-specific vaccine Vx-001.
AB  - Vx-001, an HLA-A*0201 restricted telomerase (TERT)-specific anti-tumor vaccine,
      is composed of the 9-mer cryptic TERT(572) peptide and its optimized variant
      TERT(572Y). We have previously shown that Vx-001 is non-toxic, highly immunogenic
      and in vaccinated NSCLC patients early specific immune response is associated
      with prolonged survival. The aim of the present study was to investigate the
      specific T-cell immune response against Vx-001. Fifty-five patients with chemo
      resistant advanced solid tumors were vaccinated with TERT(572Y) (2 subcutaneous
      injections) followed by TERT(572) peptide (4 subcutaneous injections) every 3
      weeks. Specific immune response was evaluated by IFN-gamma and perforin ELISpot
      and intracellular cytokine staining assays. TERT-reactive T cells were detected
      in 27 (51%) out of 53 evaluable patients after the 2nd vaccination and in 22
      (69%) out of 32 evaluable patients after the completion of 6 vaccinations. Immune
      responses developed irrespective of the stage of disease and disease status
      before vaccination. Patients with disease progression at study entry who
      developed a post-vaccination-induced immunological response had a significant
      overall survival benefit compared to the post-vaccination non-responders. The Vx
      001 vaccine is a promising candidate for cancer immunotherapy since it can induce
      a TERT-specific T-cell immune response that is associated with prolonged
      survival.

PMID- 21858534
TI  - Loss of labour productivity caused by disease and health problems: what is the
      magnitude of its effect on Spain's economy?
AB  - The aim of this study is to estimate the economic impact of the non-medical costs
      of diseases and accidents in Spain. Its main premise sustains the idea that in
      addition to the number of deaths, the loss of quality of life and the pain
      suffered by patients and their family members as a result of diseases and
      accidents, there are other indicators that provide us with a better understanding
      of their socioeconomic impact. Our analysis provides estimates of the loss of
      labour productivity in Spain as a result of health problems in 2005. Our main
      finding suggests an estimated loss amounting to over 37,969 millions euros, of
      which 9,136 millions euros are due to premature deaths, 18,577 millions to
      permanent disability and 10,255 millions to temporary disability. The loss in
      labour productivity due to accidents and health problems was estimated to a
      figure equivalent to nearly 4.2% of the Gross Domestic Product of Spain in 2005.
      This study underscores the strong economic impact of non-medical costs of
      diseases. In addition, it stresses the need for better information systems for
      collecting data that is relevant to the topic at hand.

PMID- 21858535
TI  - [Hallux rigidus].
AB  - Osteoarthritis of the first metatarsophalangeal joint is termed hallux rigidus.
      Clinical symptoms are expressed by a painful limitation of range of motion,
      finally leading to an eponymous total stiffness of the joint. Conservative
      treatment includes drug therapy, physical therapy and orthotic devices like
      insoles and footwear modification. After making use of the whole range of
      conservative treatment options, several surgical techniques are available, which
      should be considered depending on stage, patient's activity level and possible
      comorbid diseases. Open and arthroscopic techniques addressing the cartilage and
      cheilectomy can be chosen in early stages of hallux rigidus. Osteoarthritis at a
      higher stage requires further reaching techniques, e.g. Bonney-Kessel procedure
      or Watermann-Green procedure. When the complete clinical picture of hallux
      rigidus is present, arthrodesis is the gold standard. Nevertheless, alternative
      surgical treatments like arthroplasty and resection arthroplasty are being
      discussed.

PMID- 21858536
TI  - The expression and clinical significance of CLIC1 and HSP27 in lung
      adenocarcinoma.
AB  - The purpose of this research was to study the roles of chloride intracellular
      channel protein 1 (CLIC1) and heat shock protein 27 (HSP27) in the clinical
      pathology of lung adenocarcinoma and to explore whether the expression of CLIC1
      and HSP27 can be used as independent factors for the prediction of recurrence and
      prognosis after radical resection of lung adenocarcinoma. One hundred and three
      paraffin sections of lung adenocarcinoma tissues were collected, and the
      expression of CLIC1 and HSP27 was detected in these tumors using
      immunohistochemistry. The correlation of the expression of these two proteins
      with clinicopathological parameters and prognosis was statistically analyzed. In
      the 103 samples, the expression of HSP27 and CLIC1 was strongly positive in 61
      (59.2%) and 49 cases (47.6%), respectively. Statistical analysis showed that the
      expression level of HSP27 did not significantly correlate with the patient's age,
      sex, degree of tumor differentiation, T staging of tumors, and TNM staging of
      tumors (p > 0.05), whereas the expression of CLIC1 did significantly correlate
      with T staging of tumors (p = 0.029). Univariate analysis indicated that the
      patient's ECOG score, T staging, N staging, TNM staging, and CLIC1 expression
      correlated with prognosis (p = 0.031, 0.001, 0.011, 0.013, and <0.001,
      respectively). Multivariate statistical analysis showed that age, T staging, and
      CLIC1 expression were independent associated factors for predicting the 5-year
      survival rate of patients (p = 0.026, 0.004, and <0.001, respectively). Age, T
      staging, and CLIC1 expression significantly correlated with the overall survival
      of post-operative lung adenocarcinoma patients. CLIC1 may be closely associated
      with the occurrence and development of lung adenocarcinoma and may be used as an
      effective marker for predicting the prognosis of this disease.

PMID- 21858537
TI  - Evaluation of multiple serum markers in advanced melanoma.
AB  - The aim of this retrospective study was to analyse in advanced melanoma the
      potential tumor markers S-100B, melanoma inhibiting activity protein (MIA) and
      YKL-40 compared to LDH. Serum levels of S-100B, MIA, LDH and YKL-40 were measured
      in 110 patients with advanced melanoma (36 in stage IIIB/C and 74 in stage IV),
      in 66 disease-free patients and in 65 healthy controls. Results show that S-100B,
      MIA and LDH levels were significantly higher in patients with advanced melanoma
      than in disease-free patients or healthy controls. The combination of S-100B plus
      MIA had the best diagnostic sensitivity, and the addition of LDH did not further
      increase this sensitivity. MIA was an independent prognostic factor of overall
      survival. Patients with both S-100B and MIA elevated had a significant shorter
      survival than those with both S-100B and MIA under the cut-off. YKL-40 levels did
      not differentiate patients with advanced melanoma from controls. We concluded
      that the combination of MIA plus S-100B showed a better prognostic value in
      advanced melanoma compared to LDH.

PMID- 21858538
TI  - Polyphasic characterization of "Aspergillus nidulans var. roseus" ATCC 58397.
AB  - Polyphasic characterization of the echinocandin B producer Aspergillus nidulans
      var. roseus ATCC 58397 strain was carried out to elucidate its taxonomical
      status. According to its carbon source utilization and secondary metabolite
      spectrum as well as the partial beta-tubulin, calmodulin, and gamma-actin gene
      sequences, A. nidulans var. roseus belongs to the Emericella rugulosa species.
      Auxotroph mutants of A. nidulans var. roseus ATCC 58397 and E. rugulosa CBS
      171.71 and CBS 133.60 formed stable heterokaryons on minimal medium with several
      A. nidulans strains, and in the case of A. nidulans var. roseus, even
      cleistothecia were developed.

PMID- 21858539
TI  - Mortality and complication rates of percutaneous ablative techniques for the
      treatment of liver tumors: a systematic review.
AB  - OBJECTIVES: Reported rates of major complications and mortality of radiofrequency
      ablation (RFA), microwave ablation (MWA) and percutaneous ethanol injection (PEI)
      for the treatment of liver tumours were substantially heterogeneous among
      studies. The aim was to analyse the mortality and major complication rates of
      percutaneous RFA, PEI and MWA. METHODS: MEDLINE and EMBASE search from January
      1982 to August 2010. Randomised clinical trials and observational studies, age
      >18, more than 50 patients for each technique analysed, studies reporting
      mortality and major complications were included. Random effects model was
      performed, with assessment for heterogeneity and publication bias. RESULTS:
      Thirty-four studies including 9531, 1185, and 1442 patients for RFA, MWA, and
      PEI, respectively were included. For all ablative techniques pooled proportion
      mortality rate was 0.16% (95% confidence interval [CI], 0.10-0.24). Pooled
      mortality rate associated with RFA, PEI and MWA was 0.15% (0.08-0.23), 0.59%
      (0.14-1.3) and 0.23% (0.0-0.58) respectively. Pooled proportion of major
      complications was 3.29% (2.43-4.28). Major complication rates associated with
      RFA, MWA, and PEI was 4.1% (3.3-5.1), 4.6% (0.7-11.8) and 2.7% (0.28-7.4)
      respectively. CONCLUSIONS: Percutaneous RFA, PEI and MWA can be considered safe
      techniques for the treatment of liver tumours.

PMID- 21858540
TI  - Prospective comparison of short-term functional outcomes obtained after pure
      laparoscopic and robot-assisted laparoscopic sacrocolpopexy.
AB  - OBJECTIVE: To prospectively compare short-term functional outcomes achieved by
      laparoscopic or robot-assisted sacrocolpopexy for pelvic organ prolapse.
      MATERIALS AND METHODS: We prospectively collected clinical and operative data
      over 24 months for female patients who underwent either pure laparoscopic
      sacrocolpopexy (LSCP) or robot-assisted laparoscopic sacrocolpopexy (RALSCP).
      Clinical data included age, BMI and assessment of PFDI-20 score. Perioperative
      data included operative time and complications. Post-operative outcomes included
      hospital stay, length of catheterisation, pain and functional outcomes as
      assessed by clinical examination and PFDI-20 score assessment. RESULTS: Overall,
      67 women with a median age of 65 were included: 47 in the LSCP arm and 20 in the
      RALSCP arm. RALSCP was superior in terms of blood loss (median 55mls vs. 280; P =
      0.03) and strict operative time (median 125 min vs. 220; P < 0.0001), but this
      time advantage was nullified when comparing overall operating room time (215 min
      vs. 220). With a median follow-up of 16 months, the overall anatomic repair rate
      was 98.5%, and there was an improvement in overall PFDI-20 score before and after
      surgery (P = 0.001) but with no difference between the two surgical approaches.
      CONCLUSIONS: RALSCP allows for a safe and effective repair of pelvic organ
      prolapse in female patients. Whilst being equivalent to LSCP in terms of
      functional outcome, it is superior in terms of blood loss and strict operative
      time. These results are based on short-term assessment, and further studies of
      larger populations with longer follow-up and objective assessments of outcome are
      needed to make any definitive statement.

PMID- 21858541
TI  - Relationship of bone mineral density with disease activity and functional ability
      in patients with ankylosing spondylitis: a cross-sectional study.
AB  - In ankylosing spondylitis, inflammatory activity probably plays a key role in the
      pathophysiology of bone loss. The aim of the study was to investigate the
      relationship of bone mineral density (BMD) at the lumbar spine and hip region
      with some measures of disease activity and functional ability in patients with
      ankylosing spondylitis. In 80 patients with established ankylosing spondylitis,
      disease activity and functional ability were determined by C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI).
      Spinal pain and patient global health were assessed using horizontal visual
      analog scale. BMD was measured by dual-energy X-ray absorptiometry. There was a
      significant negative correlation of bone density T scores with acute-phase
      reactants (i.e., patients with lower T scores had higher level of CRP and ESR).
      That relationship was reflected more reliably at proximal femur sites than at the
      lumbar spine. There were also significant differences in ESR, BASDAI, BASFI,
      spinal pain and global health between three groups of patients according to WHO
      classification of osteoporosis (normal, osteopenic and osteoporotic).
      Significantly, more patients with osteopenia at the lumbar spine had lower BASDAI
      index than those with normal BMD (P = 0.030). Our results indicate an association
      of low BMD with high disease activity in patients with AS. Femoral BMD seems to
      be more associated with disease activity and functional ability than lumbar spine
      BMD.

PMID- 21858542
TI  - Sex differences in disease risk from reported genome-wide association study
      findings.
AB  - Men and women differ in susceptibility to many diseases and in responses to
      treatment. Recent advances in genome-wide association studies (GWAS) provide a
      wealth of data for associating genetic profiles with disease risk; however, in
      general, these data have not been systematically probed for sex differences in
      gene-disease associations. Incorporating sex into the analysis of GWAS results
      can elucidate new relationships between single nucleotide polymorphisms (SNPs)
      and human disease. In this study, we performed a sex-differentiated analysis on
      significant SNPs from GWAS data of the seven common diseases studied by the
      Wellcome Trust Case Control Consortium. We employed and compared three methods:
      logistic regression, Woolf's test of heterogeneity, and a novel statistical
      metric that we developed called permutation method to assess sex effects (PMASE).
      After correction for false discovery, PMASE finds SNPs that are significantly
      associated with disease in only one sex. These sexually dimorphic SNP-disease
      associations occur in Coronary Artery Disease and Crohn's Disease. GWAS analyses
      that fail to consider sex-specific effects may miss discovering sexual dimorphism
      in SNP-disease associations that give new insights into differences in disease
      mechanism between men and women.

PMID- 21858543
TI  - Casting of MOD inlay using rings with holes on both sides: 12~18 wt%Au-20~26Pd
      14.48~26.48Cu-40Ag-1.5Zn-0.02Ir alloys.
AB  - Using a casting ring with openings on both sides and a water-absorbent polymer,
      heterogeneity is maintained in a single casting and a precise MOD inlay can be
      produced. We produced 9 different kinds of gold-silver-palladium (Au-Ag-Pd)
      alloys by changing the ratio of palladium, gold, and copper and investing them,
      and changing parameters such as the angulation of the casting ring openings and
      the water:powder ratios to produce MOD inlay castings. We measured the expansion
      and shrinkage percentage of the castings in both the buccolingual and mesiodistal
      directions. From this experiment, we learned that precise MOD inlay castings can
      be produced using rings with 240 degrees  openings when invested in a thick mix
      having a standard water:powder ratio or using rings with 200 degrees  openings
      when invested in a thick mix having a water:powder ratio for a 12 wt%Au-20~26Pd
      20.48~26.48Cu-40Ag-1.5Zn-0.02Ir alloyes.

PMID- 21858544
TI  - Interactions between parents/carers of pre-school children and pharmacy staff
      when buying non-prescription medicines.
AB  - OBJECTIVE: Little is known about the interactions between pharmacy staff and
      parents/carers who buy nonprescription medicines for children. Responsibility for
      choice and administration of children's medicines falls to the parent/carer.
      Pharmacy advice should support safe and effective use of medicines for children.
      This paper explores the interactions between pharmacy staff and purchasers of
      children's medicines, in terms of questioning and advice giving. SETTING: Thirty
      nine community pharmacies across four Primary Care Trusts (PCTs) in England.
      METHODS: A self-completion survey and a subset of semi-structured telephone
      interviews were undertaken with parents/carers buying oral medicines for children
      aged 0-4 years. MAIN OUTCOME MEASURE: Frequency and type of questioning and
      advice given by pharmacy staff to parents purchasing nonprescription medicines.
      RESULTS: One hundred and thirty-four surveys and thirty-four interviews were
      completed: most participants were 25-44 year-old women. The majority (85%)
      reported being questioned, most often by medicines counter assistants, to
      establish the safety and suitability of the medicine. Three key questions
      (whether the medicine had been used before, the age of the child, and concurrent
      medicines), however, were not always asked. Interviews revealed self-perceptions
      of 'expert' and 'novice' users, depending on experience with the medicine
      purchased. This seemed to affect their perception of their need for questioning
      and advice from pharmacy staff. CONCLUSION: Interactions in the pharmacy
      involving the purchase of medicines for young children are varied with regard to
      questioning and advice given. This study has found that key questions are not
      always asked before a medicine is sold, and advice about using the medicine was
      given in just over one-third of encounters. Parents/carers also identified a
      range of additional information they would like to have received with their
      medicine: there was, however, no clear pattern to the type of information they
      would like. Parents reflected on the questioning and advice in terms of their
      self-perception of expertise with the medicine. Both pharmacists and their
      assistants should adopt a flexible questioning approach based on parents/carers'
      advice and information needs that respects expertise, but does not assume it.

PMID- 21858545
TI  - [Diagnostic pathways and pitfalls in acute thoracic aortic dissection: practical
      recommendations and an awareness campaign].
AB  - Despite significant improvements in the surgical therapy of acute aortic
      dissection (AAD), mortality rates in the initial phase remain unacceptably high.
      Early diagnosis and therapy are essential to improving prognosis in these
      patients. A prerequisite of prompt and correct diagnosis is"thinking of it".
      Delayed or incorrect diagnosis can often have catastrophic results.The reported
      acute chest and back pain of a tearing, stabbing nature combined with the
      physiognomy of Marfan syndrome often arouse the clinical suspicion of AAD,
      prompting immediate imaging of the thoracic aorta and therapy. For less clear
      cases, additional hints drawn from the patient history and special findings from
      the medical examination are presented schematically in a diagnostic pathway. As
      an innovative form of diagnosis, preventive echocardiographic screening in high
      risk groups is discussed.To heighten awareness of AAD and the importance of its
      correct diagnosis, the poster campaign "Thinking of it can save lives" has been
      initiated. The poster depicts AAD schematically, indicates Marfan syndrome as a
      risk factor for AAD in young people and illustrates a CT scan as the most
      frequently performed imaging technique with high sensitivity and specificity.

PMID- 21858546
TI  - [Malperfusion in aortic dissection: diagnostic problems and therapeutic
      procedures].
AB  - Malperfusion of the thoracoabdominal aorta and its side branches is a common
      complication of aortic dissection, often proving fatal. Vital organ malperfusion
      accompanying acute aortic dissection is a major cause of mortality and morbidity
      and requires timely reperfusion of the ischemic organs as well as adequate
      management of the aortic dissection. Ischemic damage to vital organs supplied by
      the thoracoabdominal aorta greatly increases the overall risk of aortic
      dissection. As initial symptoms may be subtle, malperfusion tends to be
      recognized late, and therefore accounts for a considerable percentage of
      fatalities.Effective reperfusion is not readily achieved by central aortic
      surgery alone in a certain number of patients. Various strategies have been used,
      including entry closure by central aortic surgery or stent grafting, surgical or
      catheter fenestration, bypass grafting and percutaneous stenting.Endovascular
      bare-metal stent placement is an attractive and promising treatment option since
      it is readily available, is less invasive and presents fewer risks to the
      patient.

PMID- 21858547
TI  - A model to evaluate the cytotoxicity of the fungal volatile organic compound 1
      octen-3-ol in human embryonic stem cells.
AB  - Microbial growth in damp indoor environments has been correlated with risks to
      human health. This study was aimed to determine the cytotoxicity of 1-octen-3-ol
      ("mushroom alcohol"), a major fungal volatile organic compound (VOC) associated
      with mushroom and mold odors. Using an airborne exposure technique, human
      embryonic stem cells were exposed for 1 h to different concentrations (0-1,000
      ppm) of racemic 1-octen-3-ol and its enantiomers, (R)-(-)-1-octen-3-ol and (S)
      (+)-1-octen-3-ol. Cytotoxicity was assayed using both the MTS (3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium) assay and the fluorescently tagged Calcein AM-mediated "live and
      dead" assay. Racemic 1-octen-3-ol and (S)-(+)-1-octen-3-ol exhibited greater
      cytotoxicity to the undifferentiated human cell line H1 than did (R)-(-)-1-octen
      3-ol. The inhibition concentration 50 (IC(50)) values assessed by the MTS assay
      for racemic 1-octen-3-ol, (S)-(+)-1-octen-3-ol and (R)-(-)-1-octen-3-ol were,
      respectively, 109, 98, and 258 ppm. These IC(50) values were 40-80-fold lower
      than that of vapor phase toluene, an industrial chemical used as a positive
      control in this study. Our report pioneers the modeling of human embryonic stem
      cells as an in vitro approach to screen the potential toxicity of fungal VOCs.
      Human embryonic stem cells exposed to 1-octen-3-ol, and its enantiomers in the
      vapor phase showed more cytotoxicity than those exposed to toluene.

PMID- 21858548
TI  - Effect of zinc supplementation on growth of low birth weight infants aged 1-6 mo
      in Ardabil, Iran.
AB  - OBJECTIVE: To assess the effect of zinc supplementation on growth of low birth
      weight (LBW) infants aged 1-6 mo. METHODS: LBW infants were enrolled at birth and
      randomly assigned to receive 5 mg elemental Zn per day (n = 45) or placebo (n =
      45) until 6 mo of age. They were followed monthly for information on compliance;
      anthropometric measurements were performed monthly. RESULTS: After randomization,
      5 infants from zinc group and 9 from placebo group were excluded. At 6 mo of age,
      significantly greater weight gains were observed in the zinc than in the placebo
      group (4995 +/- 74 g in zinc group vs. 3896 +/- 865 g in placebo group, p=0.036).
      Length gain during the study period improved in zinc group (16.9 +/- 8.2 cm vs.
      15.1 +/- 4.1 cm, p=0.039); after zinc supplementation head circumference were
      increased (8.7 +/- 1.4 cm vs. 7.4 +/- 1.5 cm p < 0.001). In male infants, total
      weight gain and height and head circumference gain were higher in the zinc than
      in the placebo group. However, only head circumference change was statistically
      significant. A similar trend was observed among female infants, but these
      differences were not statistically significant. There was no significant relation
      between breast-feeding status and the main outcome variables. CONCLUSIONS:
      Infants in the present study showed improvements in growth rate, but more studies
      are required in this field to confirm this fact.

PMID- 21858549
TI  - Subcutaneous fat necrosis as a complication of therapeutic hypothermia in a term
      neonate.
AB  - Subcutaneous fat necrosis of the newborn (SCFN) is a benign self-limited disorder
      commonly associated with hypothermia and perinatal asphyxia. SCFN secondary to
      therapeutic whole body hypothermia has rarely been reported. With increasing use
      of cooling for moderate to severe hypoxic ischemic encephalopathy (HIE),
      clinicians should recognize this potential complication.

PMID- 21858550
TI  - The association of polymorphisms on TGFBR1 and colorectal cancer risk: a meta
      analysis.
AB  - Epidemiological studies found inconsistent results on the association of two
      variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk.
      The present study was aimed to evaluate the association of these two variants
      with CRC susceptibility via the meta-analysis methods. For variant TGFBR1*6A,
      nine reports including 6,765 CRC patients and 8,496 unrelated controls were
      identified. The heterozygotes *6A/*9A showed a significant increased risk of CRC
      with the pooled OR was 1.12 (95% CI = 1.02-1.23), and the pooled OR for the
      homozygotes *6A/*6A was 1.13 (95% CI = 0.80-1.58) compared to the homozygotes
      *9A/*9A. However, under the dominant effect model, the TGFBR1*6A carriers showed
      a significantly increased CRC risk (pooled OR = 1.12, 95% CI = 1.03-1.23, *6A/*6A
      and *6A/*9A vs. *9A/*9A). For variant Int7G24A, three case-control studies with
      1,074 cases and 1,945 controls were found. Although no significant association
      was found for heterozygosity Int7G24A carriers with CRC risk (pooled OR = 0.97,
      95% CI = 0.67-1.42), the homozygosity A/A carriers showed a significant elevated
      risk of CRC (pooled OR = 1.68, 95% CI = 1.14-2.47) compared to G/G homozygotes.
      Under the recessive effect model, homozygotes A/A showed a 71% increase of CRC
      risk compared to the A/G and G/G genotype carriers (pooled OR = 1.71, 95% CI =
      1.17-2.51). These data strongly suggested that the two polymorphisms of TGFBR1
      may confer low-penetrance susceptibility of CRC risk.

PMID- 21858551
TI  - A developmental framework of brain and cognition from infancy to old age.

PMID- 21858552
TI  - Sequential use of sorafenib and sunitinib in advanced renal cell carcinoma: does
      the order of sequencing matter?
AB  - To investigate the sequential use of two tyrosine-kinase inhibitors (TKI),
      sorafenib (SOR) and sunitinib (SUN), in advanced renal carcinoma. We
      retrospectively analyzed the clinical outcome of 33 patients who had experienced
      progression or unacceptable toxicity after receiving either sorafenib or
      sunitinib and then switched to the other reciprocal agent. Progression-free
      survival (PFS) during the first TKI was similar regardless of drug with a median
      of 6 months in the SOR-SUN group (n = 15) and 7.5 months in the SUN-SOR group (n
      = 18). Interestingly, PFS during the second TKI was significantly longer in the
      SOR-SUN group as compared to the SUN-SOR group with median values of 11 and 3
      months, respectively (P = 0.0377; HR 0.46; 95% CI: 0.16-0.95). As a consequence,
      total PFS (sum of PFS on first and second TKI) was significantly longer in the
      SOR-SUN group than in the SUN-SOR group with medians of 20 versus 10 months,
      respectively (P = 0.0393; HR 0.47; 95% CI: 0.18-0.96). Median wash-out period
      between the two TKI was 3 weeks in both groups. Differences in baseline
      characteristics, including histology and line of treatment, were not significant,
      and toxicity was not increased during the second part of the sequence. Here, we
      show that responses can be achieved when a second TKI is given soon after a TKI
      failure in renal cancer with apparent more durable disease control when SOR is
      followed by SUN.

PMID- 21858553
TI  - Cytokine and endocrine signaling in prostate cancer.
AB  - Prostate epithelial and stromal cells develop paracrine interactions, which may
      be responsible for the occurrence and progression of prostate pathologies.
      Strikingly, stromal cells exhibit pleiotropic effects on epithelial cell growth,
      ranging from stimulation to inhibition. Steroid hormone receptors are considered
      ligand-activated transcriptional factors. Moreover, it has been suggested that
      the human androgen receptor can also be activated in the absence of surrounding
      ligands such as growth factors and cytokines. Strong evidence suggests that
      cytokines may play an important role in ligand-independent activation of androgen
      receptor in prostate cancer cells. In our view, one of the most striking finding
      in the prostate cancer development process is the relationship between
      carcinogenesis and secretion of cytokines.

PMID- 21858554
TI  - Defining nutrient and biochemical oxygen demand baselines for tropical rivers and
      streams in Sao Paulo State (Brazil): a comparison between reference and impacted
      sites.
AB  - Determining reference concentrations in rivers and streams is an important tool
      for environmental management. Reference conditions for eutrophication-related
      water variables are unavailable for Brazilian freshwaters. We aimed to establish
      reference baselines for Sao Paulo State tropical rivers and streams for total
      phosphorus (TP) and nitrogen (TN), nitrogen-ammonia (NH(4) (+)) and Biochemical
      Oxygen Demand (BOD) through the best professional judgment and the trisection
      methods. Data from 319 sites monitored by the Sao Paulo State Environmental
      Company (2005 to 2009) and from the 22 Water Resources Management Units in Sao
      Paulo State were assessed (N = 27,131). We verified that data from different
      management units dominated by similar land cover could be analyzed together
      (Analysis of Variance, P = 0.504). Cumulative frequency diagrams showed that
      industrialized management units were characterized by the worst water quality
      (e.g. average TP of 0.51 mg/L), followed by agricultural watersheds. TN and NH(4)
      (+) were associated with urban percentages and population density (Spearman Rank
      Correlation Test, P < 0.05). Best professional judgment and trisection (median of
      lower third of all sites) methods for determining reference concentrations showed
      agreement: 0.03 & 0.04 mg/L (TP), 0.31 & 0.34 mg/L (TN), 0.06 & 0.10 mg-N/L
      (NH(4) (+)) and 2 & 2 mg/L (BOD), respectively. Our reference concentrations were
      similar to TP and TN reference values proposed for temperate water bodies. These
      baselines can help with water management in Sao Paulo State, as well as providing
      some of the first such information for tropical ecosystems.

PMID- 21858555
TI  - Spatial variations in the relationships between land use and water quality across
      an urbanization gradient in the watersheds of Northern Georgia, USA.
AB  - A spatial statistical technique, Geographically Weighted Regression (GWR) is
      applied to study the spatial variations in the relationships between four land
      use indicators, including percentages of urban land, forest, agricultural land,
      and wetland, and eight water quality indicators including specific conductance
      (SC), dissolved oxygen, dissolved nutrients, and dissolved organic carbon, in the
      watersheds of northern Georgia, USA. The results show that GWR has better model
      performance than ordinary least squares regression (OLS) to analyze the
      relationships between land use and water quality. There are great spatial
      variations in the relationships affected by the urbanization level of watersheds.
      The relationships between urban land and SC are stronger in less-urbanized
      watersheds, while those between urban land and dissolved nutrients are stronger
      in highly-urbanized watersheds. Percentage of forest is an indicator of good
      water quality. Agricultural land is usually associated with good water quality in
      highly-urbanized watersheds, but might be related to water pollution in less
      urbanized watersheds. This study confirms the results obtained from a similar
      study in eastern Massachusetts, and so suggest that GWR technique is a very
      useful tool in water environmental research and also has the potential to be
      applied to other fields of environmental studies and management in other regions.

PMID- 21858556
TI  - Graves' ophthalmopathy as an indication increased the risk of hypoparathyroidism
      after bilateral thyroidectomy.
AB  - BACKGROUND: Studies have evaluated the effect of thyroidectomy on the course of
      Graves' ophthalmopathy (GO) but it is unclear how GO as an indication might
      affect surgical outcomes. We aimed to evaluate the impact of this indication on
      surgical outcomes in Graves' disease (GD). METHODS: From 1995 to 2008, 329
      patients with GD underwent thyroidectomy. Patients were stratified into two
      groups, namely, those with GO as indication (GO) and those with non-GO indication
      (non-GO). Outcomes were compared between the groups and outcomes with
      significance were further analyzed by multivariate analyses to determine
      independent factors. RESULTS: The GO group was significantly older (P < 0.001),
      had more males (P < 0.001), and fewer relapses (P < 0.001) than the non-GO group.
      It also had a higher proportion of total/near-total thyroidectomy (P < 0.001),
      despite a shorter operating time (P = 0.024) and less blood loss (P = 0.010).
      When only total/near-total thyroidectomy was considered, the GO group had
      significantly more permanent hypoparathyroidism than the non-GO group (9.2 vs.
      1.6%, P = 0.038), but the rate of permanent hypoparathyroidism was similar in the
      two groups when only those with parathyroid autotransplantation were considered.
      Other complications were similar between the two groups. By multivariate
      analysis, GO as indication was an independent risk factor for temporary (OR 1.97,
      P = 0.033) and permanent hypoparathyroidism (OR 4.76, P = 0.007). CONCLUSION: GO
      as a surgical indication (i.e., unstable or active GO requiring ophthalmic
      treatment or follow-up) was associated with increased risk of temporary and
      permanent hypoparathyroidism after bilateral thyroidectomy. Routine parathyroid
      autotransplantation may reduce the risk of permanent hypoparathyroidism in this
      select patient group.

PMID- 21858557
TI  - Transabdominal preperitoneal repair for obturator hernia.
AB  - BACKGROUND: A laparoscopic surgical approach for obturator hernia (OH) repair is
      uncommon. The aim of the present study was to assess the effectiveness of
      laparoscopic transabdominal preperitoneal (TAPP) repair for OH. METHODS: From
      2001 to May 2010, 659 patients with inguinal hernia underwent TAPP repair at in
      our institutes. Among these, the eight patients with OH were the subjects of this
      study. RESULTS: Three of the eight patients were diagnosed as having occult OH,
      and the other five were diagnosed preoperatively, by ultrasonography and/or
      computed tomography, as having strangulated OH. Bilateral OH was found in five
      patients (63%), and combined groin hernias, either unilaterally or bilaterally,
      were observed in seven patients (88%), all of whom had femoral hernia. Of the
      five patients with bowel obstruction at presentation, four were determined not to
      require resection after assessment of the intestinal viability by laparoscopy.
      There was one case of conversion to a two-stage hernia repair performed to avoid
      mesh contamination: addition of mini-laparotomy, followed by extraction of the
      gangrenous intestine for resection and anastomosis with simple peritoneal closure
      of the hernia defect in the first stage, and a Kugel hernia repair in the second
      stage. There was no incidence of postoperative morbidity, mortality, or
      recurrence. CONCLUSIONS: Because TAPP allows assessment of not only the entire
      groin area bilaterally but also simultaneous assessment of the viability of the
      incarcerated intestine with a minimum abdominal wall defect, we believe that it
      is an adequate approach to the treatment of both occult and acutely incarcerated
      OH. Two-stage hernia repair is technically feasible in patients requiring
      resection of the incarcerated intestine.

PMID- 21858558
TI  - The extended indication of parotidectomy using the modified facelift incision in
      benign lesions: retrospective analysis of a single institution.
AB  - BACKGROUND: Recently, the modified facelift incision (FLI) has gained increasing
      popularity for its cosmetic benefits in parotidectomy. However, many surgeons
      remain concerned with the adequacy of the exposure and are unwilling to use the
      FLI for anterior or superior tumors of the parotid gland because these tumors are
      closer to the superficially positioned facial nerve branch. To evaluate the
      changing trends in parotidectomy incisions for benign lesions at a single
      institute, and to compare the surgical outcomes between the modified Blair
      incision (BI) and FLI, and determine the adequacy and possible indications or
      limitations of the FLI, especially for tumors located in the anterior or superior
      parotid gland. MATERIALS AND METHODS: Retrospective study analyzed 357 patients
      who had various benign parotid diseases and underwent parotidectomy at Severance
      Hospital between January 2005 and December 2009. Revisions or recurrences and
      histologically confirmed malignancies were excluded. Tumor location was divided
      into superficial and deep lobes. The superficial lobe was subdivided into
      anterior, superior, inferior, and middle portions. Patients' profiles, surgical
      outcomes, and cosmetic satisfaction score on a scale of 0 (extremely
      dissatisfied) to 10 (extremely satisfied) were compared. RESULTS: In all, 344
      patients underwent BI or FLI. The FLI was performed increasingly each year. For
      anterior (n = 58) or superior tumors (n = 32), there was no significant
      difference between the type of incision and tumor size or complications. No
      facial nerve palsy occurred in either group. For deep-lobe tumors (n = 67), the
      mean tumor size was significantly larger in the BI group (p = 0.025). There was a
      significant difference between facial nerve palsy and tumor size (p < 0.001) but
      no significant difference between facial nerve palsy and tumor location (p =
      0.145) or the type of incision (p = 0.530). The mean scar satisfaction score was
      significantly higher in the FLI group (p <0.001). There was a positive
      correlation between the scar and deep hollow satisfaction score (Pearson
      coefficient of correlation = 0.547; p < 0.001) CONCLUSIONS: The modified facelift
      incision is feasible for most benign parotid lesions regardless of tumor
      location, even for anterior or superior tumors. Using the modified facelift
      incision may be extended with a surgeon's accumulated experience, but for a large
      deep-lobe tumor, the modified Blair incision is still considered useful.

PMID- 21858560
TI  - The procoagulant and proinflammatory plasma contact system.
AB  - The contact system is a plasma protease cascade that is initiated by coagulation
      factor XII activation on cardiovascular cells. The system starts procoagulant and
      proinflammatory reactions, via the intrinsic pathway of coagulation or the
      kallikrein-kinin system, respectively. The biochemistry of the contact system in
      vitro is well understood, however, its in vivo functions are just beginning to
      emerge. Data obtained in genetically engineered mice have revealed an essential
      function of the contact system for thrombus formation. Severe deficiency in
      contact system proteases impairs thrombus formation but does not reduce the
      hemostatic capacity of affected individuals. The system is activated by an
      inorganic polymer, polyphosphate that is released from activated platelets.
      Excessive inherited activation of the contact system causes a life-threatening
      swelling disorder, hereditary angioedema. Activation of the contact system by
      pathogens contributes to leakage in bacterial infections. Mast-cell-derived
      heparin triggers contact-system-mediated edema formation with implications for
      allergic disease states. Here we present an overview about the plasma contact
      system in occlusive and inflammatory disease and its contribution to health and
      pathology.

PMID- 21858561
TI  - [Muir-Torre syndrome. An interdisciplinary challenge].
AB  - Muir-Torre syndrome (MTS) is a rare autosomal dominant tumor syndrome
      characterized by the occurrence of tumors of the sebaceous glands and/or multiple
      keratoacanthomas in addition to internal neoplasia. Skin tumors include not only
      sebaceous adenomas and sebaceomas but also sebaceous carcinomas which are
      associated with colorectal carcinomas in over 50%, less commonly with carcinomas
      of the remaining gastrointestinal, urinary or genital tract. The underlying
      pathogenesis is a defect of the DNA mismatch repair system introducing
      microsatellite instability in tumor tissue.

PMID- 21858562
TI  - [Indications and evidence base for specific immunotherapy in childhood].
AB  - Allergic rhinitis (AR) is a common disease affecting 7-17% of children and
      adolescents who may suffer from a significantly impaired quality of life. For 100
      years subcutaneous immunotherapy (SCIT) has been used to treat AR. If patients
      are chosen carefully, a clinically relevant reduction of seasonal symptoms and
      medication use can be achieved by SCIT. Serious adverse events are rarely
      encountered during adequately performed and monitored SCIT. Sublingual
      immunotherapy (SLIT) may be used as a less painful therapeutic alternative in
      children if the administration of SCIT is impossible. Recent controlled trials
      have shown that SLIT performed over one pollen season also ameliorates seasonal
      symptoms and reduces the need for concomitant medication. Local reactions are
      frequently encountered during SLIT whereas systemic and life-threatening adverse
      events under correctly performed SLIT have not been reported so far.

PMID- 21858563
TI  - [Allergen-specific immunotherapy in pet allergy - an update].
AB  - Animal dander is a common cause of allergic rhinitis and allergic asthma in
      patients. In this regard, cats and dogs represent major causes of allergy to
      animal dander. In first line, the therapeutic options include the elimination of
      the pet from the patient's home as a (secondary) preventive step. However,
      avoidance of temporary contacts or indirect exposure to cat dander is often
      difficult, since cat-allergens are widely distributed even in non-cat-keeping
      households. In general, conventional pharmacologic therapy does not thoroughly
      prevent allergic symptoms. Therefore, allergen-specific immunotherapy (SIT)
      represents an important therapeutic option. This article highlights the current
      standards and further developments of SIT for cat-allergic patients.

PMID- 21858564
TI  - [Specific immunotherapy and atopic dermatitis. What is new?].
AB  - Although allergen-specific immunotherapy, which celebrates its 100-year
      anniversary this year, represents the only potentially corrective or curative
      therapy available in the field of allergy, this therapeutic option is rarely
      employed in patients with atopic dermatitis (AD), one of the most common chronic
      inflammatory skin diseases. The reason is the relatively low number of controlled
      studies and a high number of uncontrolled studies or case reports with quite
      heterogenous study designs focusing on the value of SIT in AD in the literature.
      However, since allergens clearly impact on the initiation and impairment of AD as
      well as flare-up of eczematous skin lesions in a subgroup of patients, selected
      patients might benefit from SIT as an additional therapeutic option. In this
      overview, we summarize the current data and provide a state-of-the-art view on
      the value of SIT in AD.

PMID- 21858565
TI  - [Pharmacoprophylaxis and co-medications in allergen-specific immunotherapy].
AB  - Drugs that are used in relation to allergen-specific immunotherapy (SIT) can be
      separated into pharmacoprophylaxis to avoid or decrease local and systemic
      adverse effects of SIT and in co-medications to treat other diseases. Regarding
      pharmacoprophylaxis, H1-antihistamines are able to reduce local and mild
      systemic, but not severe systemic side effects of SIT. H1-antihistamines do not
      attenuate the efficacy of SIT. Severe systemic side effects have been blocked in
      some cases with omalizumab; currently this agent can be used off-label during
      venom SIT. With regard to co-medication, the concomitant use of immunomodulating
      drugs during SIT must be individualized, if the effective profile and side
      effects of the immunomodulating drug are well-known and a negative effect on SIT
      is not likely. Recently approved immunosuppressive drugs and biologics are
      perceived critically due to their unpredictable immunologic effects. For forensic
      reasons cardioselective beta blockers should be discontinued although no data are
      available demonstrating adverse effects. If discontinuation is not justified and
      venom SIT is indicated, SIT can be performed while taking beta blockers. In
      contrast, ACE-inhibitors should always be stopped in patients with insect venom
      allergy.

PMID- 21858566
TI  - Changes in the cross-sectional area of deep posterior extensor muscles of the
      cervical spine after anterior decompression and fusion: 10-year follow-up study
      using MRI.
AB  - PURPOSE: To evaluate changes in the transverse area of deep posterior muscles of
      the cervical spine 10 years after anterior cervical decompression and fusion
      (ACDF), in comparison with healthy volunteers. METHODS: Thirty-one patients (22
      males, 9 females, mean age at follow-up 59.3 years, mean follow-up 12.1 years)
      who had undergone preoperative MRI and non-instrumented ACDF within levels C3-4
      to C5-6 were enrolled. 32 asymptomatic volunteers (17 males, 15 females; mean
      age, 54.7 years; mean follow-up, 11.7 years) who underwent MRI between 1993 and
      1996 served as controls. Follow-up MRI was performed on both patients and control
      subjects, and the cross-sectional areas of deep posterior muscles were measured
      digitally at levels C3-4, 4-5, and 5-6. RESULTS: The mean total cross-sectional
      area in the ACDF and control groups was 4,693.6 +/- 1,140.9 and 4,825.8 +/-
      1,048.2 mm(2) in the first MR study (P = 0.63), and 4,616.7 +/- 1,086.0 and
      5,036.7 +/- 1,105.6 mm(2) at follow-up (P = 0.13). The total cross-sectional area
      in the ACDF group slightly decreased, while that in the control group increased (
      77.1 +/- 889.7 vs. 210.9 +/- 622.0 mm(2), P = 0.14). The mean change in the cross
      sectional area had no significant correlation with clinical symptoms, including
      neck pain or JOA score. CONCLUSIONS: ACDF patients did not show a marked decrease
      in the cross-sectional area of the deep posterior cervical muscles, but as
      compared with control subjects there was a slight decrease. A decrease in the
      cross-sectional area of these muscles after ACDF may not result in the axial
      symptoms as seen in patients treated by posterior surgery.

PMID- 21858567
TI  - Validity and responsiveness of the Core Outcome Measures Index (COMI) for the
      neck.
AB  - PURPOSE: Patient-orientated outcome questionnaires are essential to evaluate
      treatment success. To compare different treatments, hospitals, and surgeons,
      standardised questionnaires are required. The present study examined the validity
      and responsiveness of the Core Outcome Measurement Index for neck pain (COMI
      neck), a short, multidimensional outcome instrument. METHODS: Questionnaires were
      completed by patients with degenerative problems of the cervical spine undergoing
      cervical disc arthroplasty before (N = 89) and 3 months after (N = 75) surgery.
      The questionnaires comprised the EuroQol-Five Dimension (EQ-5D), the North
      American Spine Society Cervical Spine Outcome Assessment Instrument (NASS
      cervical) and the COMI-neck. RESULTS: The COMI and NASS-cervical scores displayed
      no notable floor or ceiling effects at any time point whereas for the EQ-5D, the
      highest values [corrected] were reached in around 32.5% of patients at follow-up.
      With one exception (symptom-specific well-being), the individual COMI items and
      the COMI summary score correlated to the expected extent (R = 0.4-0.8) with the
      scores of the chosen reference questionnaires. The area under the curve (AUC)
      generated by ROC analysis was significantly higher for the COMI (0.96) than for
      any other instrument/subscale when self reported treatment outcome was used as
      the external criterion, dichotomised as "good" (operation helped a lot/helped)
      versus "poor" (operation helped only a little/didn't help/made things worse). The
      COMI had a high effect size (standardised response mean; SRM) (2.34) for the good
      global outcome group and a low SRM for the poor outcome group (0.34). The EQ-5D
      and the NASS-cervical lacked this ability to differentiate between the two
      groups, showing less distinct SRMs for good and poor outcome groups. CONCLUSIONS:
      This study provides evidence that the COMI-neck is a valid and responsive
      questionnaire in the population of patients examined. Further investigations
      should examine its applicability in other patient groups with less severe neck
      pain or undergoing other treatment modalities.

PMID- 21858569
TI  - Laparoscopic slit mesh repair of parastomal hernia using a designated mesh: long
      term results.
AB  - BACKGROUND: Parastomal hernia (PH) is a frequent complication of colorectal
      surgery, which incidence reaches 55% of all stoma formation. Currently, there is
      no definitive strategy for its repair. This study was designed to assess the
      outcome in patients who underwent laparoscopic PH repair using a slit
      mesh/keyhole technique. METHODS: We undertook a retrospective case review of all
      patients who underwent laparoscopic PH repair with a designed slit mesh/keyhole
      between 2005 and 2010. Three ports were placed opposite the stoma site, and
      careful adhesiolysis and hernia content reduction were performed. The parastomal
      fascial defect was measured and covered with a designated mesh. Fixation of the
      mesh was achieved with concentric tacks and transcutaneous Prolene suture.
      Recurrence was diagnosed after examination of patients by two surgeons or by
      imaging demonstrating an indolent hernia. RESULTS: Twenty-nine laparoscopic PH
      mesh repairs were performed with an average age of 63.5 (range 42-81, median 64)
      years to treat paracolostomy hernia in 18 of 29 cases (62.1%), para-ileostomy
      hernia in 10 of 29 cases (34.5%), and for an ileal conduit site hernia in 1 of 29
      cases (3.4%). The average operative time was 179 (range, 80-300; median, 180)
      min. Two operations (6.9%) were converted to an open approach. Early
      postoperative complications were documented in four patients (13.8%), including
      one elderly patient with severe comorbidities who died from postoperative sepsis
      (mortality rate, 3.4%). Only one late complication was recorded (3.4%). The
      average hospital stay was 4.7 (range, 1-19; median, 3) days. Average follow-up
      time was 28 (range, 12-53; median, 30) months. Recurrence of the hernia was found
      in 13 of 28 patients (46.4%). CONCLUSIONS: Laparoscopic slit mesh/keyhole repair
      is feasible, although it is a complex surgery reflected by extended operative
      time. The high recurrence rate suggests that technical improvement of the method
      is essential.

PMID- 21858568
TI  - Robot-assisted laparoscopic surgery of the colon and rectum.
AB  - INTRODUCTION: Laparoscopic techniques have induced a tremendous revolution in the
      field of general surgery. Recent multicenter trials have demonstrated similar
      patient-oriented and oncologic outcomes for laparoscopic colon and rectal
      resections compared with their open counterparts. Meanwhile, robotic technology
      has gradually entered the field of general surgery, allowing increased dexterity,
      improved operative view, and optimal ergonomics. The objective of this study was
      to review the current status of clinical robotic applications in colorectal
      surgery. METHODS: A systematic review of the literature using the PubMed search
      engine was undertaken to identify relevant articles. The keywords used in all
      possible combinations were: surgical robotics, robotic surgery, computer-assisted
      surgery, colectomy, sigmoid resection, sigmoidectomy, and rectal resection.
      RESULTS: Thirty-nine case series or comparative nonrandomized studies were
      identified. A specific interest for robot-assisted rectal surgery during the past
      few years was recorded in the literature. The retrieved articles included 13
      ileocecal resections, 220 right colectomies, 190 left colectomies/sigmoid
      resections, 440 anterior resections, 149 abdominoperineal/intersphincteric
      resections, and 11 total/subtotal colectomies. The clinical application of the da
      Vinci robotic system in right and left/sigmoid colectomies yielded satisfactory
      results in terms of open conversion (1.1 and 3.8%, respectively) and operative
      morbidity (13.4 and 15.1%, respectively). Robot-assisted anterior resection was
      accompanied by a considerably low conversion rate (0.4%), morbidity (9.7%), and
      adequate number of harvested lymph nodes (14.3, mean). CONCLUSIONS: Robotic
      applications in colorectal surgery are feasible with low conversion rates and
      favorable morbidity. Further studies are required to evaluate its oncologic and
      patient-oriented outcomes.

PMID- 21858570
TI  - Reply to: doi:10.1007/s00464-010-1525-9: Use of a peripheral venous catheter in
      single-incision laparoscopic surgery.

PMID- 21858571
TI  - Ki-67 and Bax expression in esophageal mucosa might have implications in ablative
      therapies for Barrett's esophagus, dysplasia, and adenocarcinoma.

PMID- 21858572
TI  - A retrospective wound review of standard four-port laparoscopic cholecystectomy:
      is there need for single-port laparoscopic surgery?
AB  - BACKGROUND: This study was designed to assess the satisfaction or otherwise of a
      proportion of the U.K. population who have undergone standard four-port
      laparoscopic cholecystectomy within the past 18 months. The results should
      indicate whether there is potential demand for a new, improved approach to
      surgery. METHODS: Patients who underwent laparoscopic cholecystectomy between
      October 2008 and October 2009 in two geographically separated general hospitals
      were identified from hospital databases. Notes were reviewed to confirm the
      technique and lack of conversion to an open procedure. Those who had immediate
      complications were excluded. A telephone questionnaire was conducted to answer
      questions related to long-term cosmetic and general satisfaction of the current
      procedure. RESULTS: Of the patients surveyed, 93% were happy or extremely happy
      with the current procedure, 48% experienced some wound-related issues (pain,
      infection), and 65% of those were at the umbilicus (a possible reflection of
      location and retrieval site for gallbladder). Cosmesis was rated less important
      than hospital cleanliness and experience of the surgeon. CONCLUSIONS: Overall
      satisfaction was high with the existing technique. The high rate of umbilical
      wound problems is an issue that will not be eradicated by introduction of single
      port laparoscopic surgery.

PMID- 21858573
TI  - Visual force feedback in laparoscopic training.
AB  - BACKGROUND: To improve endoscopic surgical skills, an increasing number of
      surgical residents practice on box or virtual reality (VR) trainers. Current
      training is focused mainly on hand-eye coordination. Training methods that focus
      on applying the right amount of force are not yet available. METHODS: The aim of
      this project is to develop a low-cost training system that measures the
      interaction force between tissue and instruments and displays a visual
      representation of the applied forces inside the camera image. This visual
      representation continuously informs the subject about the magnitude and the
      direction of applied forces. To show the potential of the developed training
      system, a pilot study was conducted in which six novices performed a needle
      driving task in a box trainer with visual feedback of the force, and six novices
      performed the same task without visual feedback of the force. All subjects
      performed the training task five times and were subsequently tested in a post
      test without visual feedback. RESULTS: The subjects who received visual feedback
      during training exerted on average 1.3 N (STD 0.6 N) to drive the needle through
      the tissue during the post-test. This value was considerably higher for the group
      that received no feedback (2.6 N, STD 0.9 N). The maximum interaction force
      during the post-test was noticeably lower for the feedback group (4.1 N, STD 1.1
      N) compared with that of the control group (8.0 N, STD 3.3 N). CONCLUSIONS: The
      force-sensing training system provides us with the unique possibility to
      objectively assess tissue-handling skills in a laboratory setting. The real-time
      visualization of applied forces during training may facilitate acquisition of
      tissue-handling skills in complex laparoscopic tasks and could stimulate
      proficiency gain curves of trainees. However, larger randomized trials that also
      include other tasks are necessary to determine whether training with visual
      feedback about forces reduces the interaction force during laparoscopic surgery.

PMID- 21858574
TI  - Partially covered self-expanding metal stent for unresectable malignant
      extrahepatic biliary obstruction: results of a large prospective series.
AB  - BACKGROUND: Endoscopic biliary stenting is a well-established palliative
      treatment in patients with unresectable malignant biliary strictures. Obstruction
      of uncovered self-expanding metal stent (SEMS) due to tumor ingrowth is the most
      frequent complication. Partially covered SEMS might increase stent patency but
      could favor complications related to stent covering, such as pancreatitis,
      cholecystitis, and migration. The aim of this study was to evaluate the efficacy
      and safety of partially covered SEMS in patients with an unresectable malignant
      biliary stricture. METHODS: Patients with malignant extrahepatic biliary
      obstruction treated endoscopically with partially covered SEMS were included in
      this multicenter, prospective, nonrandomized study. RESULTS: One hundred ninety
      nine patients were endoscopically treated with partially covered SEMS in 32
      Spanish hospitals. Clinical success after deep cannulation was 96%. Early
      complications occurred in 4% (3 pancreatitis, 2 cholangitis, 1 hemorrhage, 1
      perforation, and 1 cholecystitis). Late complications occurred in 19.5% (18
      obstructions, 10 migrations, 6 cholangitis without obstruction, 3 acute
      cholecystitis, and 2 pancreatitis), with no tumor ingrowth in any case. Median
      stent patency was 138.9 +/- 112.6 days. One-year actuarial probability of stent
      patency was 70% and that of nonmigration was 86%. Multivariate analysis showed
      adjuvant radio- or chemotherapy as the only independent predictive factor of
      stent patency and previous insertion of a biliary stent was the only predictive
      factor of migration. CONCLUSIONS: The partially covered SEMS was easily inserted,
      had a high clinical success rate, and prevented tumor ingrowth. The incidence of
      possible complications related to stent coverage, namely, migration,
      pancreatitis, and cholecystitis, was lower than in previously published series.

PMID- 21858575
TI  - Caustic injuries of the upper digestive tract: a population observational study.
AB  - BACKGROUND: Both observational and aggressive surgical strategies have been
      advocated for the treatment of corrosive injuries of the upper gastrointestinal
      tract (UGT) but the optimal management is still a dilemma. The aim of this study
      was to report our experience with caustic UGT injuries in adult patients treated
      with a surgically aggressive, endoscopy-based therapeutic protocol over a 6-year
      period. PATIENTS AND METHODS: Between January 2002 and December 2007, 315
      patients (138 men, mean age = 40 +/- 15.5 years) were referred for corrosive UGT
      injuries. Emergency endoscopy was performed in all patients at admission.
      Patients with mild injuries (grades I-IIIa) were offered nonoperative management,
      whereas emergency surgery was performed for severe injuries (grades IIIb and IV).
      Esophageal reconstruction was offered to psychologically stable patients after
      emergency esophageal resection and for esophageal strictures that failed
      endoscopic dilation. Functional failure was defined as the impossibility to
      remove the jejunostomy or/and the tracheotomy tube. RESULTS: At endoscopy 73
      (23%) patients did not have UGT injuries, 158 (50%) patients had mild injuries
      eligible for nonoperative management and 84 (27%) patients had severe injuries.
      Nonoperative management was successful in 93% of patients with mild injuries.
      Surgical exploration was eventually performed in 88 (28%) patients and resection
      was undertaken in 76 of them. Emergency mortality was 7% and all fatalities were
      patients with initial severe injuries. After a median follow-up of 6 days (range
      = 1 day-8.5 years), functional failure was recorded in 9 (3%) patients, all of
      whom had initial severe injuries. CONCLUSION: Emergency endoscopic grading of
      caustic injuries is the main factor that conditions outcome after caustic
      ingestion.

PMID- 21858576
TI  - Synchronous pyogenic liver abscess and acute cholecystitis: how to recognize it
      and what to do (emergency cholecystostomy followed by delayed laparoscopic
      cholecystectomy).
AB  - BACKGROUND: The treatment of synchronous pyogenic liver abscess (PLA) and acute
      cholecystitis (AC) may be challenging. Moreover, because of the similarity of
      symptoms and the suboptimal accuracy of ultrasound (US), PLA(s) may be
      undetected, unless a computer tomography (CT) scan is performed. The aims of this
      study were (1) to evaluate the results of emergency cholecystostomy (CS) and late
      laparoscopic cholecystectomy (LC) in such a population and (2) to identify the
      criteria for selecting patients with AC and a high risk of having synchronous
      PLA(s) for referral for a CT scan. METHODS: A retrospective analysis of the
      outcome of 12 patients with AC and PLA(s) treated by emergency CS followed by
      delayed LC from January 1996 through May 2010 at a tertiary-care university
      hospital was performed. Clinical, laboratory, and radiological data of patients
      with synchronous AC and PLA(s) are compared with those of 66 patients with
      "simple" AC. RESULTS: The association of age >55 years, temperature >38 degrees
      C, WBC count >12,000/ml, and ASAT >50 UI/l and/or ALAT >75 UI/l allows for the
      selection of patients at high risk of PLA to undergo a CT scan (sensitivity:
      100%; specificity: 86%). All treated patients had a sudden improvement within 24
      h following CS. PLA was treated in 10/12 patients (83%). Hospital stay lasted
      21.5 +/- 3.5 days. Ten patients underwent elective LC 12 +/- 4 weeks after CS
      with no conversion and 30% perioperative morbidity. Operating time was 91 min.
      Hospital stay was 1.7 days [7 patients (70%) underwent surgery as an outpatient].
      CONCLUSIONS: A simple algorithm is presented for the selection of patients with
      AC to undergo a CT scan to identify synchronous PLA. Emergency CS followed by
      delayed LC is a viable, first-line treatment option for synchronous PLA and AC.

PMID- 21858577
TI  - Video. Surgical optimisation of the gastric conduit for minimally invasive
      oesophagectomy.
AB  - BACKGROUND: Total minimally invasive oesophagectomy (MIO) is a valid alternative
      to open surgery for the management of oesophagogastric cancer and may lead to a
      more rapid restoration of health-related quality of life post surgery. However, a
      high incidence of gastric conduit failure (GCF) has also been observed which
      could be detrimental to any potential benefits of this approach. Technical
      modifications have been introduced in an attempt to reduce conduit morbidity, and
      the aim of this study was to evaluate their efficacy. METHODS: Minimally invasive
      oesophagectomy has been the procedure of choice in our unit since April 2004.
      Data on patient and surgical variables are entered onto a prospective database.
      Laparoscopic ischaemic conditioning (LIC) by ligation of the left gastric vessels
      2 weeks prior to MIO was introduced in April 2006. Extracorporeal formation of
      the gastric conduit through a minilaparotomy was offered to patients since
      January 2008. Where present, GCF was characterised as one of three types: I,
      simple anastomotic leak; II, conduit tip necrosis; and III, whole conduit
      necrosis. RESULTS: As of January 2010, 131 patients had undergone an MIO and GCF
      was observed in 21 patients (16.0%). Sixty-seven patients had LIC and 9 of them
      (13.4%) developed GCF (I, 10.4%; II, 0%; III, 3.0%) compared to 12 (18.8%) of 64
      patients who did not have LIC (I, 6.3%; II, 7.8%; III, 4.7%). A total of 43
      patients had an extracorporeally fashioned conduit and 6 (14.0%) developed GCF
      (I, 11.6%; II, 0%; III, 2.3%), whilst 88 had an intracorporeal conduit with 15
      (17.0%) developing GCF (I, 6.8%; II, 5.7%; III, 4.5%). GCF can be reduced with
      the incorporation of LIC and an extracorporeally fashioned conduit, with possible
      elimination of type II conduit tip necrosis. CONCLUSIONS: Surgical modification
      of a three-stage minimally invasive oesophagectomy technique, with the further
      incorporation of laparoscopic ischaemic conditioning and extracorporeal conduit
      formation, reduces gastric conduit morbidity, allowing the potential benefits of
      this approach to be realised.

PMID- 21858578
TI  - The impact of previous fundoplication on laparoscopic gastric bypass outcomes: a
      case-control evaluation.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a common comorbid condition
      in morbidly obese gastric bypass candidates. Unfortunately, some patients who
      ultimately present for bariatric surgery have previously undergone Nissen
      fundoplication for GERD. Many surgeons consider previous fundoplication to be a
      relative contraindication to subsequent laparoscopic Roux-en-Y gastric bypass
      (LRYGB) due to increased technical complexity and risk. We sought to compare the
      perioperative and long-term outcomes of a cohort of patients who had first
      undergone fundoplication and ultimately chose to later pursue LRYGB for morbid
      obesity (revision) to matched control patients. METHODS: Data were obtained from
      our prospectively maintained bariatric surgery database. Patients who underwent
      laparoscopic takedown of a previous fundoplication and conversion to LRYGB were
      compared to control patients who underwent primary LRYGB. For every revision
      patient, two control subjects were randomly selected from the database after
      matching for preoperative body mass index and year of surgery. RESULTS: From July
      2002 to April 2011, 14 patients underwent laparoscopic takedown of a previous
      Nissen fundoplication and then underwent LRYGB. During the same interval, 673
      patients underwent LRYGB as a primary procedure for obesity from which 28 were
      selected as controls. There were no conversions to open laparotomy in any
      patient. Subjects were similar demographically. Operating time and duration of
      hospital stay were significantly longer in revision patients. Complications were
      more frequent in revisions (36% revisions vs. 7% controls, P = 0.03). Excess
      weight loss 1-year after surgery was excellent in both groups and did not differ
      (69% revision vs. 69.6% controls, P = 0.93). CONCLUSIONS: Although associated
      with longer operating times, longer duration of hospital stay, and complications,
      LRYGB after fundoplication is feasible and safe. Long-term weight loss outcomes
      are similar to those seen following primary LRYGB. Previous fundoplication is not
      a contraindication to LRYGB.

PMID- 21858579
TI  - Surgery in space: the future of robotic telesurgery (Haidegger T, Szandor J,
      Benyo Z. Surg Endosc 2011; 25(3):681-690).

PMID- 21858580
TI  - Reply to letter to the editor: Re: Robot-assisted gastrojejunal anastomosis does
      not improve the results of the laparoscopic Roux-en-Y gastric bypass Surg Endosc
      25:597-603.

PMID- 21858581
TI  - The impact of training under different visual-spatial conditions on reverse
      alignment laparoscopic skills development.
AB  - BACKGROUND: Circumstances may arise during laparoscopic procedures in which
      alignment of the laparoscope and the instruments is off by 180 degrees , creating
      a mirror image of the operative field. It has been shown that task performance is
      degraded under these reverse-alignment conditions, and that the magnitude of
      performance impairment is directly related to laparoscopic experience and skill.
      The aim of this study was to determine if reverse-alignment surgical skills could
      be developed through training. METHODS: Twenty-two medical students were
      randomized to train in either reverse- or forward-alignment conditions on a
      standardized laparoscopic task in a video trainer (peg transfer). Baseline scores
      were attained for each group under both orientations. Subjects participated in
      three 1-h training sessions during an 8-week period. Post-training scores were
      then obtained under both alignment conditions. Pre and post-training scores were
      compared for users in each study group under both conditions. RESULTS: Post
      training assessments in the forward orientation demonstrated that subjects in the
      forward-training group improved significantly compared to pre-testing, while the
      performance of subjects in the reverse-training group did not improve. Under
      reverse-alignment conditions, both groups improved on post-test assessment, with
      dramatic improvements observed for those in the reverse-training group.
      CONCLUSIONS: Laparoscopic novices can learn to adapt to a sensorimotor
      discordance in a simulated training environment. While it is possible that skills
      developed by training under standard forward-alignment conditions can be utilized
      in situations of extreme visual-spatial discordance, the intentional development
      of reverse-alignment skills by training under these conditions may prove
      beneficial to novice surgeons.

PMID- 21858582
TI  - Length of Barrett's segment predicts success of extensive endomucosal resection
      for eradication of Barrett's esophagus with early neoplasia.
AB  - BACKGROUND: Although the efficacy and safety of extensive endomucosal resection
      (EMR) in eradicating Barrett's esophagus (BE) harbouring early neoplasia have
      been established, factors predicting efficacy remains unclear. AIM: To determine
      the complete eradication rate of Barrett's esophagus with high-grade
      intraepithelial neoplasia (HGIN) or intramucosal carcinoma (IMC), safety, and
      factors predicting complete eradication by EMR. METHODS: Patients with
      histological confirmation of Barrett's HGIN/IMC were prospectively identified.
      EMR was performed using Duette multiband ligator or cap technique by a single
      operator (NEM). RESULTS: 99 patients (81 males) with median age 67 years
      [interquartile range (IQR) 60-77 years] and median Barrett's length 4 cm (IQR 2-6
      cm) were included. Of 628 index EMRs [mean 6.3, median 5 (IQR 3-8)], 23% showed
      IMC, 58.5% showed HGIN, and 16% showed low-grade dysplasia only. A median of 8
      EMR resections per patient (IQR 6-16, 1,064 resections in 89 patients) resulted
      in complete eradication of BE harboring neoplasia in 49.4% and eradication of
      HGIN/IMC in 81% (BE <5 cm subgroup: 65% complete eradication and 91% HGIN
      eradication) at median follow-up of 18 months (range 6-27 months). On univariate
      analysis, focal dysplasia (P = 0.003) and Barrett's length <5 cm (P = 0.001) were
      predictors of complete BE eradication. Barrett's length <5 cm was the only
      significant predictor [odds ratio (OR) 3.4, standard error (SE) 0.11, P = 0.0006]
      on multiple logistic regression analysis. Strictures developed in 27% and major
      bleeding in 2% with no procedure-related perforations or mortality. CONCLUSIONS:
      Extensive EMR for removal of BE with early neoplasia is safe. Outcomes for
      complete BE eradication are modest at 49.4% and eradication of high-grade
      dysplasia at 81%. Barrett's length <5 cm is the only significant predictor of
      complete response.

PMID- 21858583
TI  - Clinical and radiological results of GSB III total elbow arthroplasty in patients
      with rheumatoid arthritis.
AB  - Total elbow arthroplasty (TEA) with the GSB III prosthesis was performed in 32
      patients (36 elbows) with rheumatoid arthritis between 2001 and 2009. At final
      follow-up, 31 patients (35 TEAs) were available for clinical and radiological
      evaluation. The mean follow-up period was 6.3 (2.0-10.3) years, with a minimum
      follow-up of 2 years. The mean Mayo elbow performance score was significantly
      improved from 48 points preoperatively to 83 points at final follow-up. The
      radiographic loosening rate was 14.3% for humeral components and 5.7% for ulnar
      components. There were 4 cases of intraoperative fracture and 1 case of humeral
      shaft fracture at 4 months after surgery. The rates for loosening and fracture
      were relatively low when compared with those in other studies of linked TEA.
      There were 2 cases of ulnar nerve palsy, but there was no deep infection or
      triceps disruption. The clinical results of TEA using the GSB III prosthesis in
      patients with rheumatoid arthritis were found to be satisfactory.

PMID- 21858584
TI  - Multiseptate gallbladder.

PMID- 21858585
TI  - To what extent do joint attention, imitation, and object play behaviors in
      infancy predict later communication and intellectual functioning in ASD?
AB  - The extent to which early social communication behaviors predict later
      communication and intellectual outcomes was investigated via retrospective video
      analysis. Joint attention, imitation, and complex object play behaviors were
      coded from edited home videos featuring scenes of 29 children with ASD at 9-12
      and/or 15-18 months. A quantitative interval recording of behavior and a
      qualitative rating of the developmental level were applied. Social communication
      behaviors increased between 9-12 and 15-18 months. Their mean level during
      infancy, but not the rate of change, predicted both Vineland Communication scores
      and intellectual functioning at 3-7 years. The two methods of measurement yielded
      similar results. Thus, early social communicative behaviors may play pivotal
      roles in the development of subsequent communication and intellectual
      functioning.

PMID- 21858586
TI  - The structure of autism symptoms as measured by the autism diagnostic observation
      schedule.
AB  - The current study tested several competing models of the autism phenotype using
      data from modules 1 and 3 of the ADOS. Participants included individuals with
      ASDs aged 3-18 years (N = 1,409) from the AGRE database. Confirmatory factor
      analyses were performed on total samples and subsamples based on age and level of
      functioning. Three primary models were tested, including a one-factor model, the
      DSM-IV model, and the anticipated DSM-V model. Results indicated all models fit
      similarly. Module 1 ratings yielded better indices of fit across all models and
      higher inter-factor correlations than Model 3. Model fits were impacted by age
      and level of functioning. The lack of differentiation between models suggests
      that the structure of ASD symptoms is complex to measure statistically.

PMID- 21858587
TI  - Cognitive impairment and abnormal behaviour related to ring chromosome 20
      aberration.

PMID- 21858588
TI  - Evidence-based social skills training for adolescents with autism spectrum
      disorders: the UCLA PEERS program.
AB  - The present study examines the efficacy and durability of the PEERS Program, a
      parent-assisted social skills group intervention for high-functioning adolescents
      with ASD. Results indicate that teens receiving PEERS significantly improved
      their social skills knowledge, social responsiveness, and overall social skills
      in the areas of social communication, social cognition, social awareness, social
      motivation, assertion, cooperation, and responsibility, while decreasing autistic
      mannerisms and increasing the frequency of peer interactions. Independent teacher
      ratings revealed significant improvement in social skills and assertion from pre
      test to follow-up assessment. Examination of durability of improvement revealed
      maintenance of gains in nearly all domains with additional treatment gains at a
      14-week follow-up assessment.

PMID- 21858589
TI  - A randomized controlled trial of conventional fraction and late course
      accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal
      cancer.
AB  - We compared the curative and side-effects in esophageal carcinoma treated by
      conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three
      dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned
      to two different radiotherapy model groups. Fifty patients were treated using CF
      three-dimensional conformal radiotherapy at a total dose of 60-68 Gy; 2 Gy/F; 5
      fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF
      treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21-27
      Gy; a total dose of 61-67 Gy; median 64 Gy). The data showed that the 1-, 2- and
      3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74,
      54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in
      LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P =
      0.454). In CF group, the incidence of radiation-induced esophagitis was lower
      than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant
      difference between rates of radiation-induced pneumonitis in CF and LCAF groups
      (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local
      control and survival rates of esophageal carcinoma patients treated with LCAF
      were slightly better than CF radiotherapy; however, the radiation side-effects in
      LCAF group were greater than those in CF group.

PMID- 21858590
TI  - A causal analysis of intra-abdominal hemorrhage after reduced-size liver
      transplantation in rat.
AB  - In this study, we analyzed causes of abdominal hemorrhage after reduced-size
      liver transplantation in rat. Healthy SD rats (weight range of 260-280 g)
      underwent liver transplantation, the donors were female and the recipients were
      male rats. The recipients were, on average, by <10 g heavier than the donors. All
      operations on donor rats were performed by the same person using unaided
      eyesight. Operations on recipient rats were performed by two persons using
      unaided eyesight. About 270 rats received reduced-size liver transplantation of
      which 44 died because of intra-abdominal hemorrhages. The distribution of
      abdominal hemorrhage sites was as follows: 28 cases with anastomotic hemorrhages
      of the inferior vena cava of the superior liver, 9 cases with subcapsular
      hemorrhage, 9 cases with tied hemorrhages from the left lateral lobe, 7 cases
      with hemorrhages from the papillary lobe, 7 hemorrhages from the triangular lobe,
      5 hemorrhages of the right suprarenal vein and lumbar veins, 4 hemorrhages caused
      by mechanical injury, 4 cuff hemorrhages of the portal vein and the inferior vein
      cava of the inferior liver, 8 anastomotic hemorrhages of the inferior vena cava
      of the superior liver and the tied hemorrhage of the left outboard lobe, and 5
      hemorrhages of the two tied points of the reduced-size liver. Ten hemorrhages
      were stopped by suture or/and ligature, and 6 were stopped by washing with or
      soaking in hot water. Results of this study will be helpful to raise success
      rates of reduced-size liver transplantation.

PMID- 21858592
TI  - DICOM for implantations--overview and application.
AB  - Surgeons have to deal with many devices from different vendors within the
      operating room during surgery. Independent communication standards are necessary
      for the system integration of these devices. For implantations, three new
      extensions of the Digital Imaging and Communications in Medicine (DICOM) standard
      make use of a common communication standard that may optimise one of the
      surgeon's presently very time-consuming daily tasks. The paper provides a brief
      description of these DICOM Supplements and gives recommendations to their
      application in practice based on workflows that are proposed to be covered by the
      new standard extension. Two of the workflows are described in detail and
      separated into phases that are supported by the new data structures. Examples for
      the application of the standard within these phases give an impression of the
      potential usage. Even if the presented workflows are from different domains, we
      identified a generic core that may benefit from the surgical DICOM Supplements.
      In some steps of the workflows, the surgical DICOM Supplements are able to
      replace or optimise conventional methods. Standardisation can only be a means for
      integration and interoperability. Thus, it can be used as the basis for new
      applications and system architectures. The influence on current applications and
      communication processes is limited. Additionally, the supplements provide the
      basis for further applications, such as the support of surgical navigation
      systems. Given the support of all involved stakeholders, it is possible to
      provide a benefit for surgeons and patients.

PMID- 21858591
TI  - An analysis of response rate and economic costs between mail and web-based
      surveys among practicing dentists: a randomized trial.
AB  - This study explored the economic costs and response rate of mail and web-based
      surveys with practicing dentists. A random sample of 6,000 practicing dentists
      was randomly assigned into three groups of 2,000: choice (mail or web-based),
      postal mail, or web-based. The Florida Tobacco Control Survey 2009, which is
      composed of 28 questions (including subject demographic questions), served as the
      survey instrument. A total of 1,232 surveys were returned by the three different
      groups (21% overall response rate). Response rates were best for the mail (26%)
      with the worst response rate coming from the Web group (11%). However, a cost
      effectiveness analysis revealed that web surveys were 2.68 times more cost
      effective.

PMID- 21858593
TI  - Suction drains, quilting sutures, and fibrin sealant in the prevention of seroma
      formation in abdominoplasty: which is the best strategy?
AB  - BACKGROUND: Seroma is the most common complication in abdominoplasty and
      abdominal ultrasound is one of the best noninvasive methods for diagnosing seroma
      formation. The aim of this study was to compare the use of suction drains,
      quilting sutures, and fibrin sealant in abdominoplasty to determine the best
      strategy to prevent seroma formation. METHODS: Forty-three female patients, aged
      20-66 years, nonsmokers, with Nahas' type III deformities, and body mass index
      (BMI) ranging from 18.0 to 24.9 kg/m(2), underwent abdominoplasty between March
      and October 2008 in a public hospital setting. The patients were randomly
      allocated to one of three treatment groups: DN group (n = 15), abdominoplasty
      with suction drains alone; QS group (n = 13), abdominoplasty with quilting suture
      between the subcutaneous tissue of the flap and musculoaponeurotic layer of the
      anterior abdominal wall; and FS group (n = 15), abdominoplasty with fibrin
      sealant. All patients underwent ultrasound examination on postoperative days 15
      and 30 for detection of abdominal fluid collections. RESULTS: The groups were
      homogeneous for age and BMI. There was a significant reduction in seroma
      formation between postoperative days 15 and 30 in the three groups (DN group, P =
      0.0003; QS group, P = 0.0011; and FS group, P = 0.0003). Seroma formation was
      significantly higher in the FS group (H = 6.04, P < 0.05) compared with the DN
      and QS groups on postoperative day 15. CONCLUSION: Seroma formation was
      significantly lower in the DN and QS groups compared with the FS group on
      postoperative day 15.

PMID- 21858594
TI  - Lazy S-curve epicanthoplasty in Asian blepharoplasty.
AB  - BACKGROUND: Ethnic characteristics of the Asian upper eyelid include the lack of
      a superior palpebral fold, excessive fat, laxity of pretarsal skin, and a medial
      epicanthal fold. We present the lazy S-curve epicanthoplasty for correction of
      the medial epicanthal fold. METHODS: The lazy S-curve incision was made as an
      entrance step. Then the connective and orbicularis oculi muscle dense fibers
      underlying the epicanthal folds were released and shifted. To reduce the tension
      of the new medial canthus, we anchored the canthus by suture fixation of both the
      subdermal and medial orbital periosteum. Rotation of the S-curve flap was settled
      as the last step. RESULTS: From December 2005 to December 2009, the authors
      corrected the epicanthal folds on the eyelids of 156 Asian patients using the
      lazy S-curve epicanthoplasty. Results were satisfactory in most of the follow-up
      cases. CONCLUSION: Lazy S-curve epicanthoplasty is a reliable and effective
      method to eliminate not only the epicanthal fold but also the undesirable
      orbicularis oculi muscle.

PMID- 21858595
TI  - Influence of age on rhinoplasty outcomes evaluation: a preliminary study.
AB  - BACKGROUND: The aim of this study was to evaluate the satisfaction of patients
      who underwent rhinoplasty by using the Rhinoplasty outcomes evaluation (ROE)
      questionnaire and determine the influence of patient age on the outcomes.
      METHODS: We conducted a longitudinal study to assess patients' pre- and
      postoperative degrees of satisfaction with their results. The study was done at a
      tertiary-care medical center. The ROE questionnaire was applied twice in the same
      visit and aimed at measuring the patient's satisfaction in both pre- and
      postoperative moments. RESULTS: The initial sample of this study was composed of
      112 patients, 61 of whom have answered the ROE questionnaire. A mean difference
      of 50.5 (P < 0.0001) was observed between the pre- and postoperative satisfaction
      scores. No statistically significant difference was observed on the mean
      difference between pre- and postoperative satisfaction scores (CHANGE) according
      to sex (P = 0.673), the follow-up time period (P = 0.629), or the kind of
      surgical procedure (P = 0.904). The mean postoperative score of the <30-year-old
      group was lower than the mean of 30 to <50-year-old (P < 0.003) and >=50-year-old
      groups (P < 0.009). CONCLUSION: The ROE questionnaire is a tool for evaluating
      the outcomes of different surgical indications for correcting nasal deformities.
      The kind of surgical procedure had no influence on the mean difference between
      pre- and postoperative satisfaction scores. By using this tool we found that the
      younger age group reported lower postoperative satisfaction scores than older
      patients.

PMID- 21858596
TI  - DIEP flap donor site versus elective abdominoplasty short-term complication
      rates: a meta-analysis.
AB  - BACKGROUND: Although over the past decade the DIEP flap has emerged as one of the
      preferred choices for autologous breast reconstruction and the donor-site closure
      has much in common with the standard abdominoplasty technique, reports on
      comparisons of the complication rates between DIEP and elective abdominoplasty
      patients are not currently available. The purpose of this study was to compare
      DIEP donor-site and elective abdominoplasty short-term complications rates, in
      support of surgical choices. METHODS: Searches of MEDLINE and CENTRAL for English
      language articles on DIEP and elective abdominoplasty (EA) published from January
      1999 through December 2009 identified 33 studies that met the inclusion criteria
      and included 3,937 patients. A random-effects model was used to calculate the
      average complication rate in the literature. RESULTS: The rate of seroma/hematoma
      in EA (16.1%, 95% confidence interval [CI] = 12.2-20.9%) was approximately four
      times the rate in DIEP flap patients (3.7%, 95% CI = 1.5-8.8%) was found from
      analyzing the data under a random-effects model. No substantial differences in
      the rates of infection, abdominal/umbilical necrosis, or wound dehiscence/delayed
      healing between the two series of patients were detected. CONCLUSIONS: This meta
      analysis reveals that DIEP donor-site complication rates were comparable to those
      in elective abdominoplasty, and, the rate of seroma in DIEP is an even lower than
      that of one of the most performed procedures in plastic surgery. We argue that
      patients presenting for a DIEP flap should be informed about this interesting
      comparison.

PMID- 21858597
TI  - Malignancies within rhinophyma: report of three new cases and review of the
      literature.
AB  - BACKGROUND: Rhinophyma, which represents the end stage of rosacea, is
      characterized by sebaceous hyperplasia, fibrosis follicular plugging, and
      telangiectasia. Although it is commonly labeled as an aesthetic problem, it may
      also determine airway obstruction and because of its nature to hide the growth of
      tumors. Due to the increasing number of reports of nonmelanoma skin types of
      cancer within rhinophyma, further concern about a higher incidence of
      malignancies in rhinophyma than in the skin of normal noses is reasonable.
      METHODS: We describe three male patients who developed malignancies (2 basal and
      1 squamous cell carcinoma) associated with rhinophyma disease. The tumors
      developed over a mean of 23.3 years after primary diagnosis of rhinophyma. One
      case had a previous history of facial skin tumor. Surgical excision with clear
      margins allowed resolution in all three patients with a mean follow-up of 34.8
      months. CONCLUSIONS: These three new cases and the review of 43 cases reported in
      the literature call attention to the clinical features of carcinomas arising in
      the context of rhinophyma, raising further concerns about the possible
      association between these two entities. The need for histologic examination of
      all surgically removed tissue in patients with rhinophyma is highlighted. Several
      macroscopic changes, including ulceration, drainage, and a rapid growth pattern,
      should alarm the physician and should be considered as suspicious of a malignant
      degeneration. Unexpected clinical modifications of a preexisting long-lasting
      silent rhinophyma could indicate the possibility of hidden malignancy rather than
      a rhinophyma itself. Although evidence of an association between the two entities
      remains inconclusive, half of the malignancies reported in our review were
      incidental findings associated with rhinophyma. Thus, since rhinophyma should not
      be considered solely a cosmetic problem, we recommend that all specimens be
      reviewed by a pathologist and if malignancy is diagnosed, re-excision with clear
      margins should be achieved when necessary with periodic follow-up.

PMID- 21858599
TI  - The blue-eyes stereotype: do eye color, pupil diameter, and scleral color affect
      attractiveness?
AB  - BACKGROUND: Blue eyes have been the embodiment of attractiveness not only for
      decades but even for centuries. The primary aim of this study was to determine
      whether iridal color, particularly color blue, can increase the attractiveness of
      a person's eye area. As a secondary aim, the study examined the impact of pupil
      diameter and scleral color on the attractiveness of the eye area. METHODS: The
      stimulus material comprised images of the eye areas of 60 women ages 15-65 years.
      A total of 80 participants rated the attractiveness of each eye area on a 7-point
      Likert scale and estimated the age of the person. The color values of the iris
      and sclera were measured. As an additional subsample, 50% of the participants
      were asked what features of each eye area they found particularly appealing.
      RESULTS: Most surprisingly, no correlation was found between iridal color and
      rated attractiveness. However, the participants mentioned the color blue more
      often as a positive aspect than other iridal colors. A high inverse correlation
      was observed between attractiveness of the eye area and age. The larger the pupil
      diameter and the whiter the scleral color, the lower was the real and perceived
      age and the higher was the attractiveness. CONCLUSION: The data showed that the
      "blue-eyes stereotype" does exist. People consider blue eyes attractive, but in
      reality, blue is rated as attractive as other iridal colors. Bright scleral color
      and large pupils positively affect attractiveness because both features are
      significantly correlated with youthfulness.

PMID- 21858600
TI  - Cardiac tissue injury resistance during myocardial infarction at adulthood by
      developmental exposure to cadmium.
AB  - It has been suggested that prenatal exposure to cadmium may alter the
      cardiovascular function during adulthood. Using the left coronary artery ligation
      model of acute myocardial infarction, we studied the cardiac function of female
      adult offspring rats exposed to cadmium (30 ppm) during gestation. The cardiac
      ischemic zone in the control and cadmium-exposed groups was measured 72 h post
      ligation using the TPT staining technique. Offspring from cadmium-treated dams
      showed a significantly smaller infarcted area compared with the control group
      (7.1 +/- 1.5 vs. 19.6 +/- 2.8%, P <= 0.05). We also performed echocardiographic
      and biochemical studies, which positively correlated with the differences
      observed previously. To evaluate whether the effects were associated to pre
      infarct tissue damage and/or angiogenic molecules, we performed histological
      studies and measured the expression of vascular endothelial growth factor (VEGF),
      and platelet endothelial cellular adhesion molecule-1 (PECAM-1). Results revealed
      a higher heart vascularization in the exposed offspring that was associated with
      an increase in PECAM and a decrease in VEGF expression. We conclude that prenatal
      exposure to cadmium induces fetal adaptive responses involving changes in the
      expression of some cardiac angiogenic molecules resulting in long-term resistance
      to infarction.

PMID- 21858601
TI  - Toward a research and action agenda on urban planning/design and health equity in
      cities in low and middle-income countries.
AB  - The importance of reestablishing the link between urban planning and public
      health has been recognized in recent decades; this paper focuses on the
      relationship between urban planning/design and health equity, especially in
      cities in low and middle-income countries (LMICs). The physical urban environment
      can be shaped through various planning and design processes including urban
      planning, urban design, landscape architecture, infrastructure design,
      architecture, and transport planning. The resultant urban environment has
      important impacts on the health of the people who live and work there. Urban
      planning and design processes can also affect health equity through shaping the
      extent to which the physical urban environments of different parts of cities
      facilitate the availability of adequate housing and basic infrastructure,
      equitable access to the other benefits of urban life, a safe living environment,
      a healthy natural environment, food security and healthy nutrition, and an urban
      environment conducive to outdoor physical activity. A new research and action
      agenda for the urban environment and health equity in LMICs should consist of
      four main components. We need to better understand intra-urban health inequities
      in LMICs; we need to better understand how changes in the built environment in
      LMICs affect health equity; we need to explore ways of successfully planning,
      designing, and implementing improved health/health equity; and we need to develop
      evidence-based recommendations for healthy urban planning/design in LMICs.

PMID- 21858603
TI  - Showing that the race model inequality is not violated.
AB  - When participants are asked to respond in the same way to stimuli from different
      sources (e.g., auditory and visual), responses are often observed to be
      substantially faster when both stimuli are presented simultaneously (redundancy
      gain). Different models account for this effect, the two most important being
      race models and coactivation models. Redundancy gains consistent with the race
      model have an upper limit, however, which is given by the well-known race model
      inequality (Miller, 1982). A number of statistical tests have been proposed for
      testing the race model inequality in single participants and groups of
      participants. All of these tests use the race model as the null hypothesis, and
      rejection of the null hypothesis is considered evidence in favor of coactivation.
      We introduce a statistical test in which the race model prediction is the
      alternative hypothesis. This test controls the Type I error if a theory predicts
      that the race model prediction holds in a given experimental condition.

PMID- 21858604
TI  - A stochastic lie detector.
AB  - Surveys on sensitive issues provide distorted prevalence estimates when
      participants fail to respond truthfully. The randomized-response technique (RRT)
      encourages more honest responding by adding random noise to responses, thereby
      removing any direct link between a participant's response and his or her true
      status with regard to a sensitive attribute. However, in spite of the increased
      confidentiality, some respondents still refuse to disclose sensitive attitudes or
      behaviors. To remedy this problem, we propose an extension of Mangat's (Journal
      of the Royal Statistical Society: Series B, 56, 93-95, 1994) variant of the RRT
      that allows for determining whether participants respond truthfully. This method
      offers the genuine advantage of providing undistorted prevalence estimates for
      sensitive attributes even if respondents fail to respond truthfully. We show how
      to implement the method using both closed-form equations and easily accessible
      free software for multinomial processing tree models. Moreover, we report the
      results of two survey experiments that provide evidence for the validity of our
      extension of Mangat's RRT approach.

PMID- 21858602
TI  - A systematic review of adherence to cardiovascular medications in resource
      limited settings.
AB  - BACKGROUND: Medications are a cornerstone of the prevention and management of
      cardiovascular disease. Long-term medication adherence has been the subject of
      increasing attention in the developed world but has received little attention in
      resource-limited settings, where the burden of disease is particularly high and
      growing rapidly. To evaluate prevalence and predictors of non-adherence to
      cardiovascular medications in this context, we systematically reviewed the peer
      reviewed literature. METHODS: We performed an electronic search of Ovid Medline,
      Embase and International Pharmaceutical Abstracts from 1966 to August 2010 for
      studies that measured adherence to cardiovascular medications in the developing
      world. A DerSimonian-Laird random effects method was used to pool the adherence
      estimates across studies. Between-study heterogeneity was estimated with an I(2)
      statistic and studies were stratified by disease group and the method by which
      adherence was assessed. Predictors of non-adherence were also examined. FINDINGS:
      Our search identified 2,353 abstracts, of which 76 studies met our inclusion
      criteria. Overall adherence was 57.5% (95% confidence interval [CI] 52.3% to
      62.7%; I(2) 0.98) and was consistent across study subgroups. Studies that
      assessed adherence with pill counts reported higher levels of adherence (62.1%,
      95% CI 49.7% to 73.8%; I(2) 0.83) than those using self-report (54.6%, 95% CI
      47.7% to 61.5%; I(2) 0.93). Adherence did not vary by geographic region, urban
      vs. rural settings, or the complexity of a patient's medication regimen. The most
      common predictors of poor adherence included poor knowledge, negative perceptions
      about medication, side effects and high medication costs. INTERPRETATION: Our
      study indicates that adherence to cardiovascular medication in resource-limited
      countries is sub-optimal and appears very similar to that observed in resource
      rich countries. Efforts to improve adherence in resource-limited settings should
      be a priority given the burden of heart disease in this context, the central role
      of medications in their management, and the clinical and economic consequences of
      non-adherence.

PMID- 21858605
TI  - Calculating and graphing within-subject confidence intervals for ANOVA.
AB  - The psychological and statistical literature contains several proposals for
      calculating and plotting confidence intervals (CIs) for within-subjects (repeated
      measures) ANOVA designs. A key distinction is between intervals supporting
      inference about patterns of means (and differences between pairs of means, in
      particular) and those supporting inferences about individual means. In this
      report, it is argued that CIs for the former are best accomplished by adapting
      intervals proposed by Cousineau (Tutorials in Quantitative Methods for
      Psychology, 1, 42-45, 2005) and Morey (Tutorials in Quantitative Methods for
      Psychology, 4, 61-64, 2008) so that nonoverlapping CIs for individual means
      correspond to a confidence for their difference that does not include zero. CIs
      for the latter can be accomplished by fitting a multilevel model. In situations
      in which both types of inference are of interest, the use of a two-tiered CI is
      recommended. Free, open-source, cross-platform software for such interval
      estimates and plots (and for some common alternatives) is provided in the form of
      R functions for one-way within-subjects and two-way mixed ANOVA designs. These
      functions provide an easy-to-use solution to the difficult problem of calculating
      and displaying within-subjects CIs.

PMID- 21858607
TI  - Radiotherapy with concurrent and adjuvant temozolomide in children with newly
      diagnosed diffuse intrinsic pontine glioma.
AB  - The purpose of this study is to evaluate the efficacy and toxicity of radiation
      therapy (RT) with concurrent temozolomide (TMZ) chemotherapy followed by adjuvant
      TMZ in children with diffuse intrinsic pontine glioma (DIPG). Newly diagnosed
      patients younger than 18 years with histologically proven DIPG were treated with
      focal radiotherapy to a dose of 54 Gy in 30 fractions along with concurrent daily
      TMZ (75 mg/m(2)/day). Four weeks after completing the initial RT-TMZ schedule,
      adjuvant TMZ (200 mg/m(2)/day, days 1-5) was given every 28 days up to six
      cycles. Responses/progressions were assessed by clinical and 2-monthly MRI follow
      up studies. Between September 2005 and September 2009, 21 patients with newly
      diagnosed histologically confirmed DIPG were eligible for this study. Median age
      at diagnosis was 6.4 years (range 4-16 years). At last update in August 2010, 17
      children have died, 1 child was alive with progressive disease and 3 with stable
      disease. Metastatic relapse was documented in the cerebral site in two patients
      and in spinal cord in two cases. The median time to progression was 7.5 months
      (range 28 days-14.5 months) and the median survival was 11.7 months (range 26
      days-17.5 months). The 1-year PFS and the 1-year OS were 33 and 50%,
      respectively. Five patients presented radiological findings compatible with
      pseudoprogression during the treatment. Haematological toxicity (Grade III/IV
      thrombocytopenia and leucopenia) was the most commonly found and led to dose
      reductions of TMZ in 58% of the patients. TMZ with radiation therapy has not
      yielded any significant improvement in outcome of children with DIPG and is
      associated with higher toxicity compared with radiotherapy alone. Novel treatment
      modalities are needed to improve the outcome of these patients.

PMID- 21858606
TI  - Neurotrophic effects of growth/differentiation factor 5 in a neuronal cell line.
AB  - The neurotrophin growth/differentiation factor 5 (GDF5) is studied as a potential
      therapeutic agent for Parkinson's disease as it is believed to play a role in the
      development and maintenance of the nigrostriatal system. Progress in
      understanding the effects of GDF5 on dopaminergic neurones has been hindered by
      the use of mixed cell populations derived from primary cultures or in vivo
      experiments, making it difficult to differentiate between direct and indirect
      effects of GDF5 treatment on neurones. In an attempt to establish an useful model
      to study the direct neuronal influence of GDF5, we have characterised the effects
      of GDF5 on a human neuronal cell line, SH-SY5Y. Our results show that GDF5 has
      the capability to promote neuronal but not dopaminergic differentiation. We also
      show that it promotes neuronal survival in vitro following a 6-hydroxydopamine
      insult. Our results show that application of GDF5 to SH-SY5Y cultures induces the
      SMAD pathway which could potentially be implicated in the intracellular
      transmission of GDF5's neurotrophic effects. Overall, our study shows that the SH
      SY5Y neuroblastoma cell line provides an excellent neuronal model to study the
      neurotrophic effects of GDF5.

PMID- 21858608
TI  - Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer
      Center experience.
AB  - Recurrent diffuse intrinsic pontine gliomas (DIPG) are traditionally treated with
      palliative care since no effective treatments have been described for these
      tumors. Recently, clinical studies have been emerging, and individualized
      treatment is attempted more frequently. However, an informative way to compare
      the treatment outcomes has not been established, and historical control data are
      missing for recurrent disease. We conducted a retrospective chart review of
      patients with recurrent DIPG treated between 1998 and 2010. Response progression
      free survival and possible influencing factors were evaluated. Thirty-one
      patients were identified who were treated in 61 treatment attempts using 26
      treatment elements in 31 different regimens. The most frequently used drugs were
      etoposide (14), bevacizumab (13), irinotecan (13), nimotuzumab (13), and valproic
      acid (13). Seven patients had repeat radiation therapy to the primary tumor.
      Response was recorded after 58 treatment attempts and was comprised of 0
      treatment attempts with complete responses, 7 with partial responses, 20 with
      stable diseases, and 31 with progressive diseases The median progression-free
      survival after treatment start was 0.16 years (2 months) and was found to be
      correlated to the prior time to progression but not to the number of previous
      treatment attempts. Repeat radiation resulted in the highest response rates
      (4/7), and the longest progression-free survival. These data provide a basis to
      plan future clinical trials for recurrent DIPG. Repeat radiation therapy should
      be tested in a prospective clinical study.

PMID- 21858609
TI  - Effects of selegiline, a monoamine oxidase B inhibitor, on differentiation of P19
      embryonal carcinoma stem cells, into neuron-like cells.
AB  - Selegiline, the irreversible inhibitor of monoamine oxidase B (MAO-B), is
      currently used to treat Parkinson's disease. However, the mechanism of action of
      selegiline is complex and cannot be explained solely by its MAO-B inhibitory
      action. It stimulates gene expression, as well as expression of a number of mRNAs
      or proteins in nerve and glial cells. Direct neuroprotective and anti-apoptotic
      actions of selegiline have previously been observed in vitro. Previous studies
      showed that selegiline can induce neuronal phenotype in cultured bone marrow stem
      cells and embryonic stem cells. Embryonal carcinoma (EC) cells are
      developmentally pluripotene cells which can be differentiated into all cell types
      under the appropriate conditions. The present study was carried out to examine
      the effects of selegiline on undifferentiated P19 EC cells. The results showed
      that selegiline treatment had a dramatic effect on neuronal morphology. It
      induced the differentiation of EC cells into neuron-like cells in a concentration
      dependent manner. The peak response was in a dose of selegiline significantly
      lower than required for MAO-B inhibition. The differentiated cells were
      immunoreactive for neuron-specific proteins, synaptophysin, and beta-III tubulin.
      Stem cell therapy has been considered as an ideal option for the treatment of
      neurodegenerative diseases. Generation of neurons from stem cells could serve as
      a source for potential cell therapy. This study suggests the potential use of
      combined selegiline and stem cell therapy to improve deficits in
      neurodegenerative diseases.

PMID- 21858610
TI  - The effects of amyloid-beta42 oligomer on the proliferation and activation of
      astrocytes in vitro.
AB  - Previous studies reported that astrocyte response to amyloid-beta (Abeta) before
      obvious neuronal damage could be detected in Alzheimer's disease (AD). It is
      suggested that astrocytes play a key role in AD pathologies. In this study, we
      investigated the effects of Abeta(42) oligomer on the proliferation and
      activation of astrocytes by in vitro experiments. The results showed that
      Abeta(42) oligomers could convert astrocytes to responsive astrocytes. It was
      revealed by MTT and ELISA assays that the viability of astrocytes gradually
      decreased, and the release of brain-derived neurotrophic factor increased with
      elevated Abeta(42) concentration and prolonged duration. Reverse-transcription
      polymerase chain reaction (RT-PCR) assay indicated that Abeta(42) oligomers
      increased the expression of glial fibers acid protein and interleukin-1beta in a
      dose-dependent but not time-dependent manner. It was showed that A8, a mouse
      monoclonal antibody, was able to protect the cultured astrocytes against the
      toxicity of Abeta(42) oligomers. The result demonstrated that A8 could inhibit
      Abeta(42) oligomers toxic effects on astrocytes and that, alone, A8 could promote
      the proliferation of astrocytes in certain time. The present study laid a
      theoretical foundation for further understanding the effects of Abeta(42) on
      astrocytes and, hence, is conducive to the theoretical understanding and clinical
      therapies of AD progression.

PMID- 21858611
TI  - Allozyme variation and population genetic structure in the carpet shell clam
      Ruditapes decussatus across the Siculo-Tunisian Strait.
AB  - This study reports on the polymorphism of 15 allozyme loci in Ruditapes
      decussatus clams collected from 11 locations along the Tunisian coasts. We
      concentrated our sampling effort around the Siculo-Tunisian region to verify if
      any population structuring exists in this region and to identify the factors that
      have shaped this structure. Measurements of genetic diversity were quantified
      both within and between populations, and the geographic variability of gene
      frequencies was analyzed. Our study shows that the Siculo-Tunisian Strait is an
      important genetic boundary between eastern and western regions, which agrees with
      findings for a variety of other species. We suggest that vicariance is a
      predominant factor shaping the current distribution of genetic diversity of R.
      decussatus, and the mixing of divergent gene pools from the eastern and western
      regions still seems to be limited by some physical and/or biological factors.

PMID- 21858612
TI  - Small wins matter in advocacy movements: giving voice to patients.
AB  - In this article, the various players are delineated in a story of a contested
      illness and patient advocacy, played out within the corridors of federal power.
      It is suggested that the mistreatment and negative attitudes that health care
      providers and others have towards those with chronic fatigue syndrome (CFS) is
      possibly due to the social construction of this illness as being a "Yuppie flu"
      disease. Institutional factors are identified that created these norms and
      attributions, as well as the multiple stakeholders and constituent groups
      invested in exerting pressure on policy makers to effect systemic change. This
      article also provides examples of how the field of Community Psychology, which is
      fundamentally committed to/based on listening to and giving voice to patients, is
      broadly relevant to patient activism communities. This approach focused, over
      time, on epidemiological studies, the name, the case definition, and ultimately
      the change in CFS leadership at the Centers for Disease Control and Prevention.
      Keys to this "small wins" approach were coalition building, use of "oppositional
      experts" (professionals in the scientific community who support patient advocacy
      goals) to challenge federal research, and taking advantage of developing
      events/shifts in power. Ultimately, this approach can result in significant
      scientific and policy gains, and changes in medical and public perception of an
      illness.

PMID- 21858613
TI  - The epigenetic turn. Some notes about the epistemological change of perspective
      in biosciences.
AB  - This article compares two different bodies of theories concerning the role of the
      genome in life processes. The first group of theories can be indicated as
      referring to the gene-centric paradigm. Dominated by an informational myth and a
      mechanistic Cartesian body/mind and form/substance dualism, this considers the
      genome as an ensemble of discrete units of information governing human body and
      behavior, and remains hegemonic in life sciences and in the public imagination.
      The second body of theories employs the principle of the extraordinary plasticity
      of the (body-)organism and emphasizes the value of the (body-)organism
      environment mutual interchange, known as 'the epigenetic approach'. This approach
      is outlined, showing a gradual, paradigmatic shift from the genecentric towards
      an epigenetic approach can be observed in the 'scientific landscape' over the
      last 20 years. The article concludes by formulating the argument that this
      'epigenetic turn' in life sciences has some important implication for renewing
      epistemological basis of social sciences.

PMID- 21858614
TI  - Ropivacaine for ultrasound-guided interscalene block: 5 mL provides similar
      analgesia but less phrenic nerve paralysis than 10 mL.
AB  - PURPOSE: Interscalene brachial plexus block (interscalene block) complications
      usually depend on the dose administered. The objective of this study was to
      determine whether ultrasound-guided interscalene block with a 5-mL dose of 0.75%
      ropivacaine would have sufficient analgesic efficacy after shoulder arthroscopic
      surgery when compared with a 10-mL dose. METHODS: Patients undergoing
      arthroscopic rotator cuff repair surgery (n = 60) were assigned randomly to one
      of two groups receiving 5 mL (Group 5) or 10 mL (Group 10) of 0.75% ropivacaine.
      Ultrasound-guided interscalene block was performed using the in-plane technique,
      and general anesthesia was administered. Time to first analgesic request was
      recorded, and the following issues were assessed in the postanesthesia care unit
      at six, 12, 24, and 48 hr postoperatively: postoperative pain as determined by a
      visual analogue scale (VAS), patient satisfaction, hemidiaphragmatic paralysis,
      other block-related complications, and postoperative nausea and vomiting (PONV).
      RESULTS: There was no significant difference between groups in time to first
      analgesic requirement (median [interquartile range] for Group 5: 16 [12-48] hr,
      Group 10: 18 [12-48] hr; P = 0.907). The postoperative pain VAS score was similar
      in both groups. The incidence of hemidiaphragmatic paralysis on postoperative
      chest x-ray was 33% in Group 5 and 60% in Group 10 (P = 0.035). However, the
      incidences of other block-related complications, PONV, and patient satisfaction
      were not significantly different between groups. CONCLUSION: Interscalene block
      performed under ultrasound guidance with 0.75% ropivacaine 5 mL showed analgesic
      efficacy similar to that with 0.75% ropivacaine 10 mL, but with a lower incidence
      of hemidiaphragmatic paralysis.

PMID- 21858615
TI  - Antibacterial activity of Capsicum annuum extract and synthetic capsaicinoid
      derivatives against Streptococcus mutans.
AB  - The inhibitory effects of the ethyl acetate extract and capsaicin (1) and
      dihydrocapsaicin (2) isolated from fruits of Capsicum annuum chili pepper type,
      and synthetic capsaicinoid derivatives (N-(4-hydroxyphenylethyl)decamide (3), (E)
      N-(4-hydroxy-3-methoxybenzyl)-3,7-dimethylocta- 2,6-dienamide (4), 4-hydroxy-3
      methoxy-N-((E)-3, 7-dimethylocta-2,6-dienyl)benzamide (5) andN-(4-hydroxy- 3
      methoxybenzyl)decamide (6) at different concentrations were evaluated against
      Streptococcus mutans. The minimum inhibitory concentration at which the ethyl
      acetate extract prevented the growth of S. mutans was 2.5 mg/mL; those of the
      isolated compounds 1 and 2 were 1.25 MUg/mL, while 3 was 5.0 MUg/mL, and 4, 5 and
      6 were 2.5 MUg/mL, respectively.

PMID- 21858616
TI  - Lack of associations of neuregulin 1 variations with schizophrenia and smooth
      pursuit eye movement abnormality in a Korean population.
AB  - Schizophrenia is a serious and disabling mental disorder with a high heritability
      rate. The human neuregulin 1 (NRG1) on 8p12 has been implicated as a candidate
      gene for schizophrenia. However, controversial results of the associations of
      NRG1 polymorphisms with schizophrenia and related phenotypes have been reported.
      In this study, four NRG1 single nucleotide polymorphisms, three in the promoter
      region, and one nonsynonymous in coding region, were genotyped in a total of 825
      subject including 435 schizophrenia cases and 390 normal controls of Korean
      ethnicity. Although logistic association analysis of NRG1 polymorphisms and
      haplotypes with schizophrenia showed a nominal association in rs4623364G > C (P =
      0.04), the significance disappeared after corrections for multiple testing
      (corrected P > 0.05). Additional case/control and multiple regression analyses in
      schizophrenia patients using a method that measures the smooth pursuit eye
      movement (SPEM) function globally based on natural logarithmic values of the
      signal/noise ratio also showed no association between NRG1 variants and SPEM
      abnormality among patients with schizophrenia (P > 0.05). Despite the need for
      further replications in other cohorts, our findings provide additional supporting
      information that four variants in NRG1 investigated in this study may not be
      associated with schizophrenia and its related SPEM function in a Korean
      population.

PMID- 21858618
TI  - Hypotensive effects of positive airway pressure ventilation in heart failure
      patients with sleep-disordered breathing.
AB  - INTRODUCTION: Obstructive sleep apnoea (OSA) as well as central sleep apnoea
      (CSA) are highly prevalent in heart failure (HF) patients. Positive airway
      pressure (PAP) therapy is usually intended to treat OSA and CSA. The aim of the
      present study was to investigate immediate hemodynamic effects of PAP therapy in
      these patients. MATERIALS AND METHODS: In 61 consecutive HF patients (NYHA >= II,
      EF <= 45%) with moderate to severe OSA or CSA (AHI >= 15/h) blood pressure (BP)
      and heart rate (HR) response to PAP therapy initiation was investigated during
      mask fitting with patients being awake and in supine position. While applying an
      endexspiratory pressure of 5.8 +/- 0.9 cm H(2)O, there was a significant decrease
      in systolic (-8.9 +/- 12.1 mmHg, p < 0.001) and diastolic BP (-5.1 +/- 9.2 mmHg,
      p < 0.001) without a change in HR (p = n.s.). RESULTS: At least a transient drop
      in mean arterial pressure <=70 mmHg was seen in 10% of these patients. Logistic
      regression analysis revealed a significant impact of baseline BP on potential BP
      drops: lower baseline BP was associated with BP drops. CONCLUSION: PAP therapy
      may cause unexpected hypotension especially in patients with low baseline BP as
      seen in HF patients treated according to current guidelines. Whether these
      hypotensive effects sustain, cause any harm to the patients and/or is responsible
      for non-acceptance or non-adherence of PAP therapy needs to be determined.

PMID- 21858620
TI  - [The ethics of ethnography revisited: learning from documentaries].
AB  - This article offers a comparison of the legal suits filed by the interviewees
      against the director of the documentary Etre et avoir (to have and to be) with
      the rights of interviewees in ethnographic investigations, focusing particularly
      on image copyrights and labor law. To say that interviewees contribute to such
      investigations in anonymity does not solve the main problem - they are crucial to
      the investigation, marginal to the analysis, and then are assigned no publication
      credits. While information about the interviewees should remain confidential,
      this article argues, that contribution and role in the making of a publication
      should not be ignored.

PMID- 21858617
TI  - A benzamide-linked small molecule HS-Cf inhibits TNF-alpha-induced interferon
      regulatory factor-1 in porcine chondrocytes: a potential disease-modifying drug
      for osteoarthritis therapeutics.
AB  - BACKGROUND: Using tumor necrosis factor-alpha (TNF-alpha)-activated porcine
      chondrocytes as a screening tool, we aim to synthesize and identify small
      molecule inhibitors preserving immunomodulatory effects as therapeutics for
      osteoarthritis (OA). METHODS: Chondrocytes were isolated from pig joints. A
      minilibrary of 300 benzamide-linked small molecules was established. The levels
      of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were measured by
      Western blot and Griess reaction, respectively. Proteoglycan degradation in
      cartilage explants was determined by histochemistry analysis. The activation of
      transcription factors and protein kinases was determined by electrophoretic
      mobility shift assays or Western blots. Zymography and real-time reverse
      transcriptase-polymerase chain reaction were used to determine enzyme activity
      and expression of matrix metalloproteinases (MMPs) and aggrecanases,
      respectively. RESULTS: Bioassay screening of benzamide-linked small molecules
      revealed that 2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide (HS-Cf) was a
      potent inhibitor of NO production and iNOS expression in TNF-alpha-stimulated
      porcine chondrocytes. HS-Cf suppressed TNF-alpha-induced activity of MMP-13 and
      expressions of several aggrecanases and prevented TNF-alpha-mediated reduction of
      collagen II. Histochemistry analysis confirmed that HS-Cf could prevent TNF-alpha
      induced degradation and release of proteoglycan/aggrecan in cartilage explants.
      Such effects by HS-Cf were likely through suppressing TNF-alpha-induced
      interferon regulatory factor-1 (IRF-1) but not nuclear factor-kappaB signaling.
      The significance of IRF-1 was further confirmed by short hairpin knockdown
      studies. CONCLUSIONS: In a minilibrary containing 300 small molecules, we
      identified a benzamide-linked small molecule, HS-Cf, that through down-regulating
      TNF-alpha-induced IRF-1 activity suppressed chondrocyte activation and prevented
      cartilage destruction. HS-Cf might be a potential disease-modifying drug for OA
      therapeutics.

PMID- 21858628
TI  - Comment on "On the threshold characteristics of the flexoelectric domains arising
      in a homogeneous electric field: the case of anisotropic elasticity" by Y.G.
      Marinov and H.P. Hinov.
AB  - It is demonstrated that the key findings of the paper by Y.G. Marinov and H.P.
      Hinov, Eur. Phys. J. E 31, 179-189 (2010), are in direct conflict with the
      general physical background of flexoelectric domains. This is caused by a
      methodological error in the theoretical analysis of the paper.

PMID- 21858629
TI  - On the coalescence of sessile drops with miscible liquids.
AB  - Sessile drops sitting on highly wettable solid substrates fuse in qualitatively
      different ways after contact, depending on the surface tension gradients between
      the mixing droplets. In early time evolution the drop coalescence can be fast or
      delayed (intermittent). In long time evolution a secondary drop formation can
      occur. We study numerically droplet dynamics during coalescence in two and three
      spatial dimensions, within a phase field approach. We discuss criteria to
      distinguish different coalescence regimes. A comparison with recent experiments
      will be done.

PMID- 21858630
TI  - [The modern technique of electronic data transmission].

PMID- 21858631
TI  - [Actual state and perspectives of e-health in Austria and international--an
      overview].
AB  - eHealth will influence the development of the Austrian health and social care
      significantly. The main part will be the implementation of an electronic health
      record. There are many hospital and outpatient information systems already
      implemented and the challenge is to enable a patient-centered communication of
      all health care providers by defining technical standards and the organizational
      and legal framework. Within this framework privacy and security have to be
      guaranteed at the highest possible level. Also, companies offering information
      systems have to improve the usability of their systems. One very important
      application is the filtering of relevant information according to a user profile
      and the optimal presentation in tables and graphs. The stepwise modular
      implementation and the use of international standards can be considered as a very
      positive approach to eHealth in Austria.

PMID- 21858632
TI  - [ELGA--the electronic health record in the light of data protection and data
      security].
AB  - The introduction of an electronic health record (ELGA) is a subject discussed for
      a long time in Austria. Another big step toward ELGA is made at the end of 2010
      on the pilot project e-medication in three model regions; other projects should
      follow. In addition, projects of the ELGA structure are sped up on the part of
      the ELGA GmbH to install the base of a functioning electronic health record.
      Unfortunately, many of these initiatives take place, so to speak, secretly, so
      that in the consciousness of the general public - and that includes not only
      patients but also physicians and other healthcare providers - always concerns
      about protection and security of such a storage of health data arouse. In this
      article the bases of the planned act are discussed taking into account the data
      protection and data security.

PMID- 21858633
TI  - [Remote telemedical management in chronic heart failure--hitches and
      opportunities].
AB  - Prognosis of chronic heart failure has improved but remains severe. Modern
      disease management for ambulatory patients includes telemedical approaches, which
      have shown positive effects on morbidity and mortality both for device-assisted
      monitoring and for nurse telephone support. Current technology is feasible for
      comfortable and extensive real-time transmission of patient data. Daily
      monitoring of symptoms, vital signs, and information from cardiac implants should
      enable the health care specialist to detect early worsening of the disease and
      initiate treatment. Appropriate clinical application of telemedicine to the
      individual patient and local health care structure is a challenge.

PMID- 21858634
TI  - [Hypertension short message service].
AB  - Hypertension Short Message Service is a new tool for disease management aimed at
      improving the success of the doctor's daily routine in hypertension treatment
      both in terms of the quality of hypertension assessment and concerning the
      efficacy of treatment. At present there is a wide and disappointing difference
      between the results of treatment in routine work [1] and in clinical trials [2,
      3] even when the same cohort of patients is treated by the same therapists. The
      efficacy rate in daily routine is about 20-35% as compared to 70-85% during
      trials. Assuming this gap is due to differences in disease management we
      integrated short message service and Internet applications into a new
      hypertension management tool (Blutdrucksms). According to our registry data
      "Blutdrucksms" is very successful: More than 80% of our hypertensive patients
      were treated to target. In June 2008, we implemented the SMS-Blood Pressure
      Protocol, and in October 2010, we analyzed the data of all "Blutdrucksms" users
      available in our registry. By then a total of 568 patients - 44% female and 56%
      male - had sent their self-recorded blood pressure readings as short messages to
      the SMS-Center; 75% of these patients had had at least one organ damage (left
      ventricular hypertrophy, increase in intima media thickening or carotid plaque).
      Mean casual blood pressure, recorded before enrolment into the SMS-program, was
      152/83. It had improved to 136/80 mmHg by October 2010. The mean of the self
      recorded blood pressures of the last month of participation was 128/76 mmHg and a
      heart rate of 69 beats per minute; 85% of all hypertensive patients had their
      pressures at treatment goal. Thus, we assume that "Blutdrucksms" is an excellent
      tool to improve the efficacy of antihypertensive disease management in routine
      work. We assume that the success is due to the enhanced communication between
      patient and doctor via SMS. As we are aware of the weakness of registry analysis
      we try to set up a controlled prospective study to compare "Blutdrucksms" users
      to non-users.

PMID- 21858635
TI  - [Perspectives of mobile communication in the management of diabetics].
AB  - Sufficient control of blood glucose levels has been demonstrated to be associated
      with improved long-term outcome in patients with diabetes. Recent advances in
      interface technology allow transfer of measurement data to mobile devices, which
      enables control, multiple access, and storage of these data and virtually links
      patients and care-giving physicians. The possibility of alerting predefined
      addressee in case of measurements below or above certain limits offers some sort
      of security that cannot be obtained by simply penning a single value to a
      scratchpad. Therefore, treating physicians are able to follow the therapeutic
      course in an easy and finally time-independent manner. Furthermore, physical
      contact is not necessary, which may be favorable especially for elderly,
      sometimes immobile patients.

PMID- 21858636
TI  - Tick-borne encephalitis: new paradigms in a changing vaccination environment.
AB  - The International Scientific Working Group on Tick-Borne Encephalitis (ISW TBE)
      held its 13th Annual Meeting in February 2011 to discuss epidemiological
      developments, news in TBE research, initiatives of the European Union,
      vaccination-immune response, clinical cases and TBE consequences, awareness of
      TBE prevention and the role of the ISW TBE to break vaccination fatigue. TBE may
      be considered a complex system, characterized by an intricate interplay between
      tick biology and socioeconomic conditions. The same may be said about vaccination
      behaviour. Thus, although the facts are simple--vaccination is the best
      prevention--the socioeconomic conditions keep changing, and with them the ability
      or willingness of people to get vaccinated. The ISW TBE is part of this complex
      system, and because the world keeps changing--so should the strategies.

PMID- 21858637
TI  - Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis
      C patients with normal ALT levels: a matched case-control study.
AB  - BACKGROUND: The antiviral effect of pegylated interferon (Peg-IFN) plus ribavirin
      combination therapy in chronic hepatitis C (CHC) patients with normal alanine
      aminotransferase (ALT) levels (N-ALT) has been reported to be equivalent to that
      for patients with elevated ALT levels (E-ALT). However, the actual antiviral
      effect in N-ALT patients remains obscure because efficacy can be overestimated in
      patients with an advantageous background. METHODS: In this study, 386 patients
      were extracted, for a matched case-control study, from 1320 CHC patients treated
      with Peg-IFN alpha-2b plus ribavirin combination therapy; 193 N-ALT patients [116
      with hepatitis C virus genotype 1 (HCV-1), 77 with HCV genotype 2 (HCV-2)] were
      matched with 193 E-ALT patients by a propensity score method using the variables
      of age, sex, IFN treatment history, body mass index, and platelet counts.
      RESULTS: On multivariate analysis for sustained virological response (SVR) in N
      ALT patients, younger age, low HCV RNA level at baseline, and HCV-2 were
      significant factors. The matched case-control study showed that the SVR rates of
      N-ALT patients were equivalent to those of E-ALT patients; at 49 and 40% in the
      HCV-1 group (P = 0.146), and 78 and 81% in the HCV-2 group (P = 0.691). However,
      in N-ALT patients with non-SVR, approximately 40% showed ALT elevation at 24
      weeks post-treatment. CONCLUSION: Our findings indicate that the antiviral effect
      of Peg-IFN plus ribavirin therapy in N-ALT patients is comparable to that for E
      ALT patients irrespective of their advantageous background; however, the
      application of this therapy for N-ALT patients, especially for those with HCV-1,
      should be considered carefully.

PMID- 21858638
TI  - Cancer stem cell theory in gastrointestinal malignancies: recent progress and
      upcoming challenges.
AB  - A growing body of evidence supports the notion that malignant tumors are
      heterogeneous and contain diverse subpopulations of cells with unique
      characteristics including the ability to initiate a tumor and metastasize. This
      phenomenon might be explained by the so-called cancer stem cell (CSC) theory.
      Recent technological developments have allowed a deeper understanding and
      characterization of CSCs. Even though the application of this theory to
      hematopoietic malignancies and solid tumors holds promise for new ways to treat
      cancer, it also brings some skepticism. Efficacious therapeutic approaches
      targeting the CSC population should be explored to overcome therapeutic failure
      and improve patient outcomes. This review will focus on the intrinsic and
      extrinsic regulation of CSCs, as well as the development of therapeutic
      approaches against CSCs, predominantly focusing on gastrointestinal malignancies.

PMID- 21858639
TI  - Plant induced defenses depend more on plant age than previous history of damage:
      implications for plant-herbivore interactions.
AB  - Herbivore-induced plant responses can significantly change as a function of plant
      developmental stage and previous history of damage. Yet, empirical tests that
      assess the combined role of multiple damage events and age-dependent constraints
      on the ability of plants to induce defenses within and among tissues are scarce.
      This question is of particular interest for annual and/or short-lived perennial
      plant species, whose responses to single or multiple damage events over a growing
      season are likely to interact with ontogenetic constraints in affecting a plant's
      ability to respond to herbivory. Using Plantago lanceolata and one of its
      specialist herbivores, Junonia coenia, we examined the effect of plant ontogeny
      (juvenile vs. mature developmental stages) and history of damage (single and
      multiple damage events early and/or late in the season) on plant responses to
      leaf damage. Plant responses to herbivory were assessed as induced chemical
      defenses (iridoid glycosides) and compensatory regrowth, in both above- and below
      ground tissues. We found that constitutive concentration of iridoid glycosides
      markedly increased as plants matured, but plant ability to induce chemical
      defenses was limited to juvenile, but not mature, plant stages. In addition,
      induced defenses observed 7 d following herbivory in juvenile plants disappeared
      5 wk after the first herbivory event, and mature plants that varied considerably
      in the frequency and intensity of damage received over 5 wk, did not differ
      significantly in their levels of chemical defenses. Also, only small changes in
      compensatory regrowth were detected. Finally, we did not observe changes in below
      ground tissues' defenses or biomass a week following 50% removal of leaf tissues
      at either age class or history of damage. Together, these results suggest that in
      P. lanceolata and perhaps other systems, ontogenetic trajectories in plant growth
      and defenses leading to strong age-dependent induced responses may prevail over
      herbivore-induced indirect interactions.

PMID- 21858640
TI  - Biomolecular structure refinement using the GROMOS simulation software.
AB  - For the understanding of cellular processes the molecular structure of
      biomolecules has to be accurately determined. Initial models can be significantly
      improved by structure refinement techniques. Here, we present the refinement
      methods and analysis techniques implemented in the GROMOS software for
      biomolecular simulation. The methodology and some implementation details of the
      computation of NMR NOE data, (3)J-couplings and residual dipolar couplings, X-ray
      scattering intensities from crystals and solutions and neutron scattering
      intensities used in GROMOS is described and refinement strategies and concepts
      are discussed using example applications. The GROMOS software allows structure
      refinement combining different types of experimental data with different types of
      restraining functions, while using a variety of methods to enhance conformational
      searching and sampling and the thermodynamically calibrated GROMOS force field
      for biomolecular simulation.

PMID- 21858641
TI  - Revision surgery for patellofemoral problems: should we always resurface?
AB  - BACKGROUND: Routine patellar resurfacing performed at the time of knee
      arthroplasty is controversial, with some evidence of utility in both TKA
      (tricompartmental) and bicompartmental knee arthroplasty. However, whether one
      approach results in better implant survival remains unclear. QUESTIONS/PURPOSES:
      We asked whether (1) routine patellar resurfacing in TKAs resulted in lower
      cumulative revision rates compared to bicompartmental knee arthroplasties, (2)
      patella-friendly implants resulted in lower cumulative revision rates than
      earlier designs, and (3) bicompartmental knee arthroplasties revised to TKAs had
      higher cumulative revision rates than primary TKAs. PATIENTS AND METHODS: From a
      community-based joint registry, we identified 8135 patients treated with 9530
      cemented, all-polyethylene patella TKAs and 627 bicompartmental knee
      arthroplasties without patellar resurfacing. We compared age, gender, year of
      index procedure, diagnosis, cruciate status, revision, and revision reason.
      RESULTS: TKAs had a lower cumulative revision rate for patella-only revision than
      bicompartmental knee arthroplasties (0.8% versus 4.8%). Adjusting for age,
      bicompartmental knee arthroplasties were 6.9 times more likely to undergo
      patellar revision than TKAs. There was no difference in the cumulative revision
      rate for patella-only revisions between patella-friendly and earlier designs. The
      cumulative revision rate for any second revision after a patella-only revision
      was 12.7% for bicompartmental knee arthroplasties while that for primary TKAs was
      6.3%. CONCLUSIONS: Bicompartmental knee arthroplasties had higher revision rates
      than TKAs. Femoral component design did not influence the cumulative revision
      rate. Secondary patella resurfacing in a bicompartmental knee arthroplasty
      carried an increased revision risk compared to resurfacing at the time of index
      TKA. To reduce the probability of reoperation for patellofemoral problems, our
      data suggest the patella should be resurfaced at the time of index surgery.

PMID- 21858642
TI  - Surface replacement of the hip can result in decreased acetabular bone stock.
AB  - BACKGROUND: The recent interest in hip resurfacing arthroplasty is motivated by
      its potential advantages over THA. One advantage of hip resurfacing arthroplasty
      is that it conserves bone on the femoral side; however, it is unclear whether it
      does so on the acetabular side. QUESTIONS/PURPOSES: We determined whether the
      amount of acetabular reaming and acetabular bone removal required for hip
      resurfacing arthroplasty is equal to, less than, or greater than that for THA.
      PATIENTS AND METHODS: We prospectively evaluated the femoral neck size of 180
      hips at the time of primary THA in an identical manner to when carrying out a hip
      resurfacing arthroplasty. Based on the femoral neck measurement, we determined
      the minimum cup size that would be used and reamer size required if the hip was
      undergoing a resurfacing. We compared this to the reamer size actually required
      to prepare the acetabulum for the THA cup. We calculated the difference between
      the predicted reaming size for resurfacing and the actual reaming size to
      determine the effect of resurfacing on acetabular bone stock. RESULTS: Overall,
      71%, 57%, and 41% of THAs would have had extra acetabular bone removed to implant
      a hip resurfacing arthroplasty cup with a line-to-line (0-mm), 1-mm, or 2-mm
      press fit, respectively. CONCLUSIONS: When compared to THA, hip resurfacing
      arthroplasty commonly results in additional acetabular bone resection.

PMID- 21858643
TI  - Effect of the insect growth regulator diflubenzuron on the predator Podisus
      nigrispinus (Heteroptera: Pentatomidae).
AB  - Podisus nigrispinus (Dallas) (Heteroptera: Pentatomidae) is a common natural
      predator of defoliating caterpillars in agricultural and forest systems.
      Insecticides acting as growth regulators of insect pests can indirectly affect
      their predators through consumption of contaminated prey. We examined the
      reproductive performance of P. nigrispinus fed on caterpillars of Anticarsia
      gemmatalis Hubner (Lepidoptera: Noctuidae) reared on soybean leaves exposed to
      the chitin synthesis inhibitor, diflubenzuron. Caterpillars of A. gemmatalis were
      fed for 12 h with treated soybean leaves and offered to adults of the predator P.
      nigrispinus over five consecutive days. The fertility of P. nigrispinus was
      reduced when feeding on diflubenzuron treated caterpillars, especially at the
      beginning of the reproductive period, but recovered 3 weeks later. The effects of
      diflubenzuron ingestion on the life table parameters of P. nigrispinus included
      an increase in the period taken to double the population size, and reductions in
      the intrinsic rate of population increase, generation duration, and net
      reproductive rate. Diflubenzuron therefore had an indirect negative effect on the
      reproduction and the population dynamics of the non-target predator P.
      nigrispinus. Clearly, its use in integrated pest management requires further
      evaluation.

PMID- 21858644
TI  - Effects on survival and reproduction of Porcellio dilatatus exposed to different
      Cd species.
AB  - The woodlouse Porcellio dilatatus (Crustacea) is a suitable model organism as a
      biological indicator for the toxic effects evaluation induced by pollutants
      exposure in the environment. In this study, the influence of cadmium (Cd) species
      on survival and reproduction of isopods was investigated. Survival, growth and
      reproductive parameters (time to pregnancy, pregnancy duration, pregnancy and
      abortion occurrence, number of juveniles per female and juvenile weight) were
      recorded after isopods were exposed to two species of Cd deployed in food:
      Cd(Cys)(2) and Cd(NO(3))(2). There was a difference between survival rates of
      exposed males and females to both Cd species but in the case of Cd(NO(3))(2)
      these differences were more accentuated, with females having higher survival
      rates. In the presence of both metal species a reduction in the number of
      pregnancies and pregnancy duration was observed, while in the case of Cd(Cys)(2)
      all pregnancies were inconclusive. The number of juveniles delivered per female
      fed with Cd(NO(3))(2) contaminated food was lower than in the control, whereas
      the juvenile weights were higher. To the best of our knowledge, the present study
      is the first toxicity test demonstrating that metal speciation affects
      reproduction in isopods. Cd(Cys)(2) showed to be the most toxic of the
      contaminants tested in this long term exposure and capable of jeopardizing the
      reproduction efforts of isopods.

PMID- 21858645
TI  - Reliability of the method of levels for determining cutaneous temperature
      sensitivity.
AB  - Determination of the thermal thresholds is used clinically for evaluation of
      peripheral nervous system function. The aim of this study was to evaluate
      reliability of the method of levels performed with a new, low cost device for
      determining cutaneous temperature sensitivity. Nineteen male subjects were
      included in the study. Thermal thresholds were tested on the right side at the
      volar surface of mid-forearm, lateral surface of mid-upper arm and front area of
      mid-thigh. Thermal testing was carried out by the method of levels with an
      initial temperature step of 2 degrees C. Variability of thermal thresholds was
      expressed by means of the ratio between the second and the first testing,
      coefficient of variation (CV), coefficient of repeatability (CR), intraclass
      correlation coefficient (ICC), mean difference between sessions (S1-S2diff),
      standard error of measurement (SEM) and minimally detectable change (MDC). There
      were no statistically significant changes between sessions for warm or cold
      thresholds, or between warm and cold thresholds. Within-subject CVs were
      acceptable. The CR estimates for warm thresholds ranged from 0.74 degrees C to
      1.06 degrees C and from 0.67 degrees C to 1.07 degrees C for cold thresholds. The
      ICC values for intra-rater reliability ranged from 0.41 to 0.72 for warm
      thresholds and from 0.67 to 0.84 for cold thresholds. S1-S2diff ranged from -0.15
      degrees C to 0.07 degrees C for warm thresholds, and from -0.08 degrees C to 0.07
      degrees C for cold thresholds. SEM ranged from 0.26 degrees C to 0.38 degrees C
      for warm thresholds, and from 0.23 degrees C to 0.38 degrees C for cold
      thresholds. Estimated MDC values were between 0.60 degrees C and 0.88 degrees C
      for warm thresholds, and 0.53 degrees C and 0.88 degrees C for cold thresholds.
      The method of levels for determining cutaneous temperature sensitivity has
      acceptable reliability.

PMID- 21858646
TI  - Novel surface molecularly imprinted sol-gel polymer applied to the online solid
      phase extraction of methyl-3-quinoxaline-2-carboxylic acid and quinoxaline-2
      carboxylic acid from pork muscle.
AB  - A new molecularly imprinted polymer (MIP), selective for major metabolites of
      quinoxaline-1,4-dioxides was firstly prepared by combining surface molecular
      imprinting technique with the sol-gel process. Methyl-3-quinoxaline-2-carboxylic
      acid (MQCA) was used as template, 3-aminopropyltriethoxysilane as functional
      monomer, and tetraethoxysilicane as cross-linker. The MIP was characterized by
      Fourier transform infrared and evaluated through static adsorption experiments.
      The results indicated that MIP had high adsorption capacity, fast binding
      kinetics for MQCA, and the polymer showed a high degree of cross-reactivity for
      quinoxaline-2-carboxylic acid (QCA). The MIP was then applied as a selective
      sorbent in an online solid phase extraction (SPE) coupled with high-performance
      liquid chromatography (HPLC). For a 50-mL sample solution, enrichment factors of
      1,349 and 1,046 for QCA and MQCA, respectively, and limits of detection (S/N=3)
      of 0.8 and 2 ng L(-1) for QCA and MQCA, respectively, were obtained
      (corresponding to 0.02 and 0.04 ng g(-1) in solid samples for final 100 mL of
      sample solutions of 5 g of pork). The sample preparation protocol was simplified
      and only included one step extraction with acetonitrile (MeCN) after the release
      of target analytes through acidic hydrolysis without further sample cleanup. The
      new MIP-SPE-HPLC method was successfully applied to the quantification of trace
      QCA and MQCA in pork muscle with good recoveries ranging from 67% to 80% and RSD
      below 8%.

PMID- 21858647
TI  - DNA-templated fluorescent silver nanoclusters.
AB  - In this review, we discuss the synthesis and applications of DNA-templated
      fluorescent silver nanoclusters in aqueous solution. Various oligonucleotide
      sequences or conformations have been utilized to synthesize silver nanoclusters
      with excellent fluorescence properties. The range of applications has expanded
      greatly, from live cell staining and the detection of metal ions and small
      biomolecules to the detection of DNA or proteins.

PMID- 21858648
TI  - Phylogenetic assessment of culture collection strains of Thiobacillus thioparus,
      and definitive 16S rRNA gene sequences for T. thioparus, T. denitrificans, and
      Halothiobacillus neapolitanus.
AB  - The 16S rRNA gene sequences of 12 strains of Thiobacillus thioparus held by
      different culture collections have been compared. A definitive sequence for the
      reference type strain (Starkey; ATCC 8158(T)) was obtained. The sequences for
      four examples of the Starkey type strain were essentially identical, confirming
      their sustained identity after passage through different laboratories. One strain
      (NCIMB 8454) was reassigned as a strain of Halothiobacillus neapolitanus, and a
      second (NCIMB 8349) was a species of Thermithiobacillus. These two strains have
      been renamed in their catalog by the National Collection of Industrial and Marine
      Bacteria. The 16S rRNA gene sequence of the type strain of Halothiobacillus
      neapolitanus (NCIMB 8539(T)) was determined and used to confirm the identity of
      other culture collection strains of this species. The reference sequences for the
      type strains of Thiobacillus thioparus and Halothiobacillus neapolitanus have
      been added to the online List of Prokaryotic Names with Standing in Nomenclature.
      Comparison of the 16S rRNA gene sequences available for strains of Thiobacillus
      denitrificans indicated that the sequence for the type strain (NCIMB 9548(T))
      should always be used as the reference sequence for new and existing isolates.

PMID- 21858649
TI  - Variations in exopolysaccharide production by Rhizobium tropici.
AB  - Rhizobium tropici, a legume-symbiont soil bacterium, is known for its copious
      production of exopolysaccharide (EPS). Many aspects of this organism's growth and
      EPS production, however, remain uncharacterized, including the influence of
      environment and culturing conditions upon EPS. Here, we demonstrate that R.
      tropici EPS chemical composition and yield differ when grown with different
      substrates in a defined minimal medium in batch culture. Exopolysaccharide was
      quantified from R. tropici grown using arabinose, glucose, sucrose, mannitol,
      fructose, or glutamate as a sole carbon source. All tested substrates produced
      plenteous amounts of exopolysaccharide material. Variations in pH and carbon-to
      nitrogen (C/N) ratio also resulted in assorted cell growth and exopolysaccharide
      production differences. We found that optimizing the C/N ratio has a greater
      impact upon R. tropici EPS production than upon R. tropici growth. A maximum EPS
      yield of 4.08 g/L was realized under optimized conditions, which is large even in
      comparison with other known rhizobia. We provide evidence that the chemical
      composition of R. tropici EPS can vary with changes to the growth environment.
      The composition of glucose-grown EPS contained rhamnose-linked residues that were
      not present in arabinose-grown EPS.

PMID- 21858650
TI  - The use of nicardipine prolonged release implants (NPRI) in microsurgical
      clipping after aneurysmal subarachnoid haemorrhage: comparison with endovascular
      treatment.
AB  - BACKGROUND: Nicardipine prolonged release implants (NPRI) have been shown to
      decrease the incidence of cerebral vasospasm and infarcts significantly in
      patients after aneurysmal subarachnoid haemorrhage (SAH) following microsurgical
      clipping. Yet, the comparison with results after endovascular coiling is lacking.
      This study was conducted to determine the differences in the incidence of
      cerebral vasospasm and infarctions between those two treatment modalities
      METHODS: The design of this investigation reflects a case-control study; 27
      patients suffering from acute SAH were treated by microsurgical clipping and
      received an intracisternal implantation of NPRI. Twenty-seven matching
      consecutive patients after microsurgical treatment without implantation of NPRI
      or endovascular treatment, respectively, served as controls. The incidence of
      angiographic vasospasm and cerebral infarctions were documented. RESULTS: All
      groups were comparable concerning demographics and severity of SAH. Twenty-four
      of 81 patients developed angiographic vasospasm (>33% constriction). The
      incidence of vasospasm was 48%, 44% and 11% for patients after endovascular
      treatment, microsurgical clipping without NPRI and microsurgical clipping with
      NPRI, respectively. New cerebral infarctions occurred in 28%, 22% and 7% of the
      treated patients, respectively. A good clinical recovery 1 year after the initial
      bleeding (modified Rankin scale 0-2) was seen in 48%, 50% and 77% of the treated
      patients, respectively. CONCLUSION: The use of NPRI during microsurgical clipping
      was confirmed to be safe and effective. Patients who received intracisternally
      implanted NPRI during clipping after aneurysmal SAH yielded significantly lower
      vasospasm and infarction rates, and showed a better clinical outcome when
      compared with clipping without NPRI and also when compared with endovascular
      coiling.

PMID- 21858651
TI  - Bevacizumab in the treatment of high-grade gliomas: an overview.
AB  - Angiogenesis is a process that is integral to the pathogenesis of high-grade
      gliomas. Bevacizumab, a humanized monoclonal antibody against vascular
      endothelial growth factor has emerged as an important therapeutic agent. Data
      from clinical trials in both recurrent and newly-diagnosed gliomas have shown
      improved radiological responses and quality of life with acceptable morbidity.
      However, an improvement in overall survival has not yet been seen and there are
      concerns on possible change in the pattern of relapse following therapy. Several
      unanswered questions remain including the dose, timing and sequencing that
      warrant further research.

PMID- 21858652
TI  - Roost type influences torpor use by Australian owlet-nightjars.
AB  - Australian owlet-nightjars (Aegotheles cristatus; ~50 g) are one of only a few
      avian species that roost in cavities year-round and regularly enter torpor.
      Cavity roosts act as thermal buffers, and roost type likely affects energy
      expenditure of small birds. We used radiotelemetry to locate diurnal winter roost
      sites of owlet-nightjars in central Australia and to measure body (T (b)) and
      skin (T (skin)) temperature. We also recorded ambient temperature inside (T (IN))
      and outside roosts. Individual owlet-nightjars used one to seven different roosts
      (tracking time 3-10 weeks), selecting either rock crevices (four birds) or tree
      hollows (four birds), or switching between the two roost types (seven birds).
      Rock crevices (T (IN) +9 degrees C to +33 degrees C) were warmer and thermally
      more stable than tree hollows (T (IN) -4.0 degrees C to +37 degrees C). Torpor,
      often expressed by a reduction of T (skin)/T (b) by >10 degrees C for 3-4 h at
      dawn, was influenced by roost selection; torpor use in tree hollows was almost
      twice that in rock crevices. Despite the potential energy savings accrued from
      roosting in well-insulated cavities, owlet-nightjars roosted in tree hollows more
      often (65% bird days, n = 398) than in rock crevices (35% bird days, n = 211).
      Lower costs of arousal from torpor via passive rewarming and basking and
      decreased risk of predation are two possible explanations for the preference to
      roost in tree hollows. We provide the first evidence for the influence of cavity
      roost selection on torpor use in a free-ranging bird and show that roost
      selection and thermal biology are strongly interrelated in determining energy
      expenditure.

PMID- 21858653
TI  - Magnetic resonance diffusion tensor imaging (MRDTI) of the optic nerve and optic
      radiations at 3T in children with neurofibromatosis type I (NF-1).
AB  - BACKGROUND: Optic pathway glioma (OPG) is a characteristic hallmark of
      neurofibromatosis type I (NF-I). OBJECTIVE: To evaluate the feasibility of
      magnetic resonance diffusion tensor imaging (MRDTI) at 3T to detect abnormalities
      of the optic nerves and optic radiations in children with NF-I. MATERIALS AND
      METHODS: 3-T MRDTI was prospectively performed in 9 children with NF-I (7 boys, 2
      girls, average age 7.8 years, range 3-17 years) and 44 controls (25 boys, 19
      girls, average age 8.1 years, range 3-17 years). Fractional anisotropy (FA) and
      mean diffusivity were determined by region-of-interest analysis for the optic
      nerves and radiations. Statistical analysis compared controls to NF-I patients.
      RESULTS: Two NF-I patients had bilateral optic nerve gliomas, three had
      chiasmatic gliomas and four had unidentified neurofibromatosis objects (UNOs)
      along the optic nerve pathways. All NF-I patients had statistically significant
      decreases in FA and elevations in mean diffusivity in the optic nerves and
      radiations compared to age-matched controls. CONCLUSION: MRDTI can evaluate the
      optic pathways in children with NF-I. Statistically significant abnormalities
      were detected in the diffusion tensor metrics of the optic nerves and radiations
      in children with NF-I compared to age-matched controls.

PMID- 21858654
TI  - New targeted therapies in pituitary carcinoma resistant to temozolomide.
AB  - To evaluate the antitumoral efficacy of everolimus in pituitary carcinoma
      resistant to temozolomide, the correlation with mammalian target of rapamycin
      (mTOR) signaling in the tumor and to present recent advances and future
      treatments of pituitary carcinomas. Pituitary carcinomas are rare and largely
      unresponsive to current treatment options. Recent reports on the antitumoral
      efficacy of temozolomide in some such patients are encouraging, yet most patients
      appear to show resistance to its actions. As a potential alternative, the mTOR
      inhibitor, everolimus, has been shown to potently inhibit pituitary cell
      proliferation highlighting mTOR inhibition as a promising therapeutic approach
      for pituitary carcinomas. We described the tumoral effects of a combination
      therapy with everolimus (5 mg/day) and octreotide (30 mg/month) and the mTOR
      signalling expression in a patient with pituitary ACTH carcinoma, compared to 17
      other ACTH adenomas. Clinical and biochemical evaluation were performed every
      month, and imaging after 3 month of treatment. mTOR signaling was assessed by
      microarray expression analysis of each of the 18 adenoma tissues. Combined
      therapy failed to control pituitary tumor growth and ACTH secretion. Slight
      activation of mTOR signaling was found in all ACTH tumors alongside important
      variations between tumors. Low antitumor efficacy shown by everolimus might be
      explained by the weak activation of mTOR pathway in ACTH tumors. Everolimus
      treatment was inefficient at controlling secretion and tumor growth of one ACTH
      pituitary carcinoma. More clinical cases, with mTOR signalling expression
      analysis of the tumor, must be published before any conclusions can be drawn.

PMID- 21858655
TI  - Optical coherence tomographic comparison of neointimal coverage between sirolimus
      and resolute zotarolimus-eluting stents at 9 months after stent implantation.
AB  - The Resolute zotarolimus-eluting stent (ZES-R) has a thinner stent strut with
      biocompatible polymer than first generation drug-eluting stents. However, minimal
      optical coherence tomography (OCT) data exists about vascular responses after ZES
      R implantation. This study investigated OCT findings in ZES-R implantation and
      compared them to those in sirolimus-eluting stent (SES) implantation. A total of
      123 lesions (43 ZES-R and 80 SES) in 111 patients were evaluated with OCT at 9
      months after stent implantation. Strut apposition, neointimal hyperplasia (NIH)
      thickness, and stent coverage on each stent strut were evaluated. Mean NIH
      thickness was significantly greater in ZES-R-treated lesions than in SES-treated
      lesions (166 +/- 73 MUm vs. 96 +/- 63 MUm, respectively, P < 0.001). The
      percentage of uncovered strut was significantly lower in ZES-R-treated lesions
      than in SES-treated lesions (4.4 +/- 4.8% vs. 10.3 +/- 13.2%, respectively, P =
      0.05). The percentage of malapposed struts was also significantly lower in ZES-R
      treated than in SES-treated lesions (0.1 +/- 0.4% vs. 1.5 +/- 4.2%, respectively,
      P = 0.002). Intracoronary thrombus was less frequently detected in ZES-R-treated
      lesions (4.7% vs. 30.0%, respectively, P = 0.001). ZES-R showed a lower incidence
      of uncovered or malapposed stent struts and intracoronary thrombus than SES at 9
      month follow-up OCT examination. Compared with SES, ZES-R may elicit more
      favorable vascular responses at the expense of an increased neointimal
      proliferation.

PMID- 21858656
TI  - Carotid stenosis evaluation by 64-slice CTA: comparison of NASCET, ECST and CC
      grading methods.
AB  - Purpose is to evaluate the intraobserver and interobserver variability of the
      North American Symptomatic Carotid Endarterectomy Trial (NASCET), European
      Carotid Surgery Trial (ECST) and Common Carotid (CC) methods, which are used to
      measure the degree of ICA stenosis, using 64-slice CT angiography and to compare
      the measurements made by these three methods. 88 cases (111 carotid arteries)
      were included in the study. Carotid CTA was performed by a 64 slice scanner
      (Toshiba, Aqullion 64).Two radiologists measured the degree of carotid stenosis
      by using NASCET, ECST and CC methods. Intraobserver and interobserver variability
      of each method was determined by intraclass correlation coefficient (ICC), Bland
      Altman plots and kappa and linear weighted kappa statistics. The relation between
      the measurements was assessed by correlation coefficient (with linear and
      quadratic methods). Correlation coefficients showed that there is linear
      correlation between the measurements made by the three methods. The degree of
      stenosis measured with the NASCET method had the lowest value, while the
      corresponding values measured with the ECST and CC methods were close to each
      other. ICC and Bland-Altman plots showed high intra and inter observer agreement
      for NASCET, ECST and CC methods whereas kappa statistics showed moderate to
      substantial agreement. CC method had slightly higher agreement when compared with
      the other two methods. Intra and interobserver agreement is high for NASCET, ECST
      and CC methods however CC method has a slightly higher reproducibility. There is
      linear correlation between the measurements made by the three methods.

PMID- 21858657
TI  - Long-term swimming in an inescapable stressful environment attenuates the
      stimulatory effect of endurance swimming on duodenal calcium absorption in rats.
AB  - Endurance swimming is known to increase duodenal calcium absorption in normal
      rats and bone strength in estrogen-deficient rats. Because the stress resulting
      from forced training often attenuates the stimulatory effect of exercise,
      swimming in an inescapable chamber should reveal both the positive effect of the
      exercise and the negative effect of stress. In the work reported herein, swimming
      rats showed no signs of stress during 2 weeks of training. However, stress
      response gradually developed thereafter and peaked at weeks 6 and 7. In rats
      swimming for 2 weeks, transcellular duodenal calcium transport was enhanced ~2
      fold. In contrast, calcium absorption was reduced in rats swimming for 8 weeks,
      consistent with the absence of swimming-induced upregulation of calcium
      transporter genes in the 8-week group. In conclusion, prolonged stress hindered
      the stimulatory effect of swimming on duodenal calcium absorption, and thus
      endurance exercise should be performed without forced training or stress to
      retain its beneficial effect on calcium metabolism.

PMID- 21858658
TI  - Properties of secreted protease from vegetative Trichoderma atroviride mycelia
      cultivated with protein inducer reveal a complex protein-recognition mechanism.
AB  - In this study, the submerged cultivation of Trichoderma atroviride with protein
      substrate (bovine serum albumin, casein, ovalbumin, etc.) led to the secretion of
      protease activity (PA) into the medium. The secretion started within 30 h and
      rose to the maximum after 72-h cultivation. It continued upon the prolonged
      cultivation (up to 8 days) with lower secreted PA. Zymography of the secreted
      protease (SDS-PAGE with 0.2% gelatine), revealing high molecular weight (m.w.)
      protease(s) (~200 kDa) with high autolytic activity as the only secretory
      product. Enzymological characteristics of high m.w. proteases elicited by
      different inducer proteins were surprisingly different, suggesting that mycelia
      can recognize not only the presence of inducer proteins but also some qualitative
      characteristics. Low m.w. protease(s), as found from  other studies was(were)
      seen after prolonged cultivation only, as a band with m.w. about 36 kDa.
      Expression of known Trichoderma spp. genes encoding secreted proteases, prb1 and
      proA, showed that only prb1 was expressed after 3-4 days of cultivation, i.e.,
      after the early-secretion phase. The secretory activity of the earlier phase was
      impaired by tunicamycin and brefeldin A and was significantly stimulated by
      uncoupler. The existence of a biphasic fungal secretory response and the protein
      quality recognition represent previously unrecognized processes.

PMID- 21858659
TI  - Lymph node ratio and pN staging in patients with node-positive breast cancer: a
      report from the Korean breast cancer society.
AB  - Patients with node-positive breast cancer are currently classified according to
      pN stage. Lymph node ratio (LNR), the ratio of positive to total removed lymph
      nodes, maybe a more useful prognostic factor in these patients. We therefore
      compared LNR and pN staging as prognostic factors in patients with node-positive
      breast cancer. Using two large prospective databases of the Korean Breast Cancer
      Registry (KBCR) and the Asan Medical Center (AMC) Breast Cancer Center of
      patients with LN-positive breast cancer from 1988 to 2005, we compared the
      ability of LNR and pN stage to predict patient survival by Cox regression
      analysis in the overall patient cohort and in subgroups categorized by age and
      intrinsic subtype. Patients were categorized into low- (<= 0.20), intermediate-
      (>0.20 and <= 0.65), and high-risk (>0.65) LNR groups. The difference in
      mortality risk was greater among LNR groups than among patients staged pN1, pN2,
      and pN3, as assessed by disease-free survival (DFS), cancer-specific survival
      (CSS), and overall survival (OS) rates. In contrast to LNR risk categories, the
      survival curves for pN1 and pN2 stage patients overlapped in those aged <35 years
      and those with her2/neu-enriched or triple-negative tumors. These findings were
      validated by analyzing a nationwide registry of 15,488 node-positive patients,
      which showed that patients with pN1 and intermediate LNR risk had poorer DFS (HR
      1.7, 95% CI 1.4-2.2) and CSS (HR 1.6, 95% CI 1.1-2.2) than patients with pN2 and
      low LNR risk. LNR is a better predictor of prognosis than pN stage in women with
      breast cancer, especially in high-risk patients, including younger women and
      women with her2/neu-enriched or triple-negative tumors. Treatment decisions
      should be based on LNR rather than on pN stage.

PMID- 21858660
TI  - Molecular detection of breast cancer metastasis in sentinel lymph nodes by
      reverse transcriptase polymerase chain reaction (RT-PCR): identifying, evaluating
      and establishing multi-marker panels.
AB  - The potential advantage of using quantitative reverse transcriptase polymerase
      chain reaction (qRT-PCR) methodology to detect metastasis in sentinel lymph nodes
      (SLNs) of breast cancer (BC) patients was evaluated in this prospective study. We
      measured the expression of relevant gene transcripts in SLNs using an innovative
      algorithm and compared the results of single-marker assays versus multi-marker
      assays with conventional histological detection methods. SLNs from women aged >=
      18 years diagnosed with unilateral BC were examined by haematoxylin-eosin
      staining and immunohistochemistry and analysed for transcripts of several
      relevant genes using qRT-PCR (learning group). Four candidate panels of expressed
      transcript combinations with high sensitivity and specificity were selected for
      further investigation. The candidate panels were then validated using SLNs from a
      second group of BC patients (validation group). In the learning group, 74/314 SLN
      sections from 150 patients were positive for metastasis by histology. The
      transcripts analysed showed the following individual sensitivities/specificities:
      cytokeratin 19 (CK19) 94.6%/97.9%; mammaglobin 1 (MGB1) 82.4%/91.7%; mammaglobin
      2 (MGB2) 82.4%/96.7%; carcinoembryonic antigen (CEA) 71.6%/97.5%; EPCAM
      (epithelial cell adhesion molecule) 91.9%/97.1%; and NY-BR-1 82.4%/93.8%. The
      optimal panel based on the predefined criteria comprised four markers: CK19,
      MGB1, EPCAM, and NY-BR-1, of which >= 2 had to be positive (95.9% sensitivity,
      95.0% specificity, 85.5% positive predictive value (PPV), and 98.7% negative
      predictive value (NPV)). Overall concordance with histology was 95.2%. In the
      validation group, 84/315 SLN sections from 235 patients were histologically
      positive, and panel sensitivity, specificity and overall accuracy were 88.1, 95.2
      and 93.3%, respectively, at the SLN section level. In conclusion, molecular
      staging using expression patterns of relevant transcripts in SLNs could serve as
      a useful complement to standard diagnostic work-up in BC patients. The proposed
      flexible multi-parametric approach does not improve the overall accuracy compared
      with the single-marker approach. However, it overcomes several limitations of the
      previously reported molecular assays for SLN diagnosis.

PMID- 21858661
TI  - FAN1 variants identified in multiple-case early-onset breast cancer families via
      exome sequencing: no evidence for association with risk for breast cancer.
AB  - We are interested in the characterisation of previously undescribed contributions
      to the heritable component of human cancers. To this end, we applied whole-exome
      capture, followed by massively parallel sequence analysis to the germline DNA of
      two greater than third-degree affected relatives from four multiple-case, early
      onset breast cancer families. Prior testing for variants in known breast cancer
      susceptibility, genes in these families did not identify causal mutations. We
      detected and confirmed two different variants in the DNA damage repair gene FAN1
      (R377W, chr15:31197995 C>T and R507H, chr15:31202961 G>A [hg19]) which were not
      present in dbSNP131. In one family, FAN1 R377W, predicted to be damaging by SIFT
      and PolyPhen2, was present in all six tested members with cancer (five with
      breast cancer, one with malignant melanoma). In another family, FAN1 R507H,
      predicted to be damaging by SIFT but benign by PolyPhen2, was observed in one of
      two tested members with breast cancer. We genotyped FAN1 R377W and R507H variants
      across 1417 population-based cases and 1490 unaffected population-based controls
      (frequency-matched for age). These variants were rare in the Australian
      population (minor allele frequencies of 0.0064 and 0.010, respectively) and were
      not associated with breast cancer risk (OR = 0.80, 95% CI[0.39-1.61], P = 0.50
      and OR = 0.74, 95% CI[0.41-1.29], P = 0.26, respectively). Analysis of breast
      cancer risks for relatives of case and control carriers did not find evidence of
      an increased risk. Despite the biological role of FAN1, the plausibility of its
      role as a breast cancer predisposition gene, and the possible deleterious nature
      of the identified variants, these two variants do not appear to be causal for
      breast cancer. Future studies to extend the genetic analysis of FAN1 will further
      explore its possible role as a breast cancer susceptibility gene.

PMID- 21858662
TI  - Free vascularized metacarpal bone graft combined with extended dorsal metacarpal
      artery flap for phalangeal bone and soft tissue loss: case report.
AB  - A 45-year-old man suffered from a complex bone and soft tissue defect of the
      middle phalanx of his left middle finger after an electric saw injury. Here, we
      present the patient's clinical and radiological outcomes after reconstruction
      with a free vascularized metacarpal II bone graft and an extended distally based
      second dorsal metacarpal artery skin flap (DMCA). To our knowledge, this is the
      first description of a free vascularized metacarpal bone graft combined with DMCA
      for distal finger reconstruction.

PMID- 21858663
TI  - Role of combined use of potassium citrate and tamsulosin in the management of
      uric acid distal ureteral calculi.
AB  - In this article, we investigated the effect of the combined use of tamsulosin and
      potassium citrate (Uralyt-U((r))) for the treatment of uric acid stones in the
      distal ureter. The study was designed as a prospective, double blind randomized
      controlled trial. A total of 191 adult patients with radiolucent distal ureteral
      calculi were recruited. We included patients with solitary stones >=5 mm with
      mild or moderate hydronephrosis and a normal contralateral tract. The patients
      were randomized into four equal groups (the placebo, tamsulosin, Uralyt-U((r)),
      and the combined treatment groups). The patients were treated for a maximum
      duration of 4 weeks or until stone expulsion. The stone size in all groups ranged
      from 5 to 11 mm (7.69 +/- 1.7 mm). The total expulsion rate of the stones was
      significantly lower in the control group (26.1%) compared with that of any of the
      other three groups (68.8, 58.7, and 84.8% respectively) (P < 0.05). Meanwhile,
      the difference between the Uralyt-U((r)) group and the combined treatment group
      was also statistically significant (P < 0.05). When we studied the patients with
      stones >8 mm as a separate subgroup to find the effect of the used drugs on the
      relatively large stones, we detected that the expulsion rate of these stones was
      significantly higher in the patients who received the combined treatment in
      comparison with any of the other three groups (P < 0.05). In conclusion, the use
      of urinary alkalization with tamsulosin can increase the frequency of spontaneous
      passage of distal ureteral uric acid stones especially those of 8-11 mm.

PMID- 21858664
TI  - The role of input-output modality compatibility in task switching.
AB  - Input-output (I-O) modality compatibility refers to the similarity of stimulus
      modality and modality of response-related sensory consequences. A previous study
      found higher switch costs in task switching in I-O modality incompatible tasks
      (auditory-manual and visual-vocal) than in I-O modality compatible tasks
      (auditory-vocal and visual-manual). However, these tasks had spatially compatible
      S-R mappings, which implied dimensional overlap (DO). DO may have led to
      automatic activation of the corresponding compatible responses in the incorrect
      response modality, thus increasing interference effects. The present study was
      aimed to examine the influence of DO on I-O modality compatibility effects. In
      two experiments, we found that I-O modality compatibility affects task switching
      even in tasks without DO, which even tended to result in further increased
      modality influences. This finding suggests that I-O modality mappings affect
      response selection by affecting between-task cross-talk not on the level of
      specific response codes but on the level of modality-specific processing
      pathways.

PMID- 21858665
TI  - Ankle proprioception is not targeted by exercises on an unstable surface.
AB  - Laboratory study using a repeated measures design. The aim of this study was to
      determine if ankle proprioception is targeted in exercises on unstable surfaces.
      Lateral ankle sprain (LAS) has recurrence rates over 70%, which are believed to
      be due to a reduced accuracy of proprioceptive signals from the ankle.
      Proprioceptive exercises in rehabilitation of LAS mostly consist of balancing
      activities on an unstable surface. The methods include 100 healthy adults stood
      barefoot on a solid surface and a foam pad over a force plate, with occluded
      vision. Mechanical vibration was used to stimulate proprioceptive output of
      muscle spindles of triceps surae and lumbar paraspinal musculature. Each trial
      lasted for 60 s; vibration was applied from the 15th till the 30th second.
      Changes in mean velocity and mean position of the center of pressure (CoP) as a
      result of muscle vibration were calculated. Results show that on foam, the effect
      of triceps surae vibration on mean CoP velocity was significantly smaller than on
      a solid surface, while for paraspinal musculature vibration the effect was bigger
      on foam than on solid surface. Similar effects were seen for mean CoP
      displacement as outcome. Exercises on unstable surfaces appear not to target
      peripheral ankle proprioception. Exercises on an unstable surface may challenge
      the capacity of the central nervous system to shift the weighting of sources of
      proprioceptive signals on balance.

PMID- 21858666
TI  - Association between regional differences in muscle activation in one session of
      resistance exercise and in muscle hypertrophy after resistance training.
AB  - The purpose of this study was to examine if the regional difference in muscle
      hypertrophy after chronic resistance training is associated with muscle
      activation after one session of resistance exercise. Twelve men performed one
      session of resistance exercise of elbow extensors. Before and immediately after
      the exercise, transverse relaxation time (T2)-weighted magnetic resonance (MR)
      images of upper arm were recorded to evaluate the muscle activation along its
      length. In the MR images, T2 for the pixels within the triceps brachii muscle was
      quantified. The number of pixels with T2 greater than the threshold (mean + 1SD
      of T2 before the exercise) was expressed as the ratio to the number of pixels
      occupied by the muscle (%activated area). Another 12 subjects completed 12 weeks
      of training intervention (3 days per week), which consisted of the same program
      variables as used in the experiment for the T2 measurement. The cross-sectional
      areas of the triceps brachii before and after the training intervention were
      measured from MR images of upper arm. The %activated area of the triceps brachii
      induced by one session of the exercise was found to be significantly lower in the
      distal region than the middle and proximal regions. Similarly, the relative
      increase in muscle cross-sectional area after the 12 weeks of training
      intervention was significantly less in the distal region than the middle and
      proximal regions. The results suggest that the regional difference in muscle
      hypertrophy after chronic resistance training is attributable to the regional
      difference in muscle activation during the exercise.

PMID- 21858667
TI  - Streptomyces ghanaensis pleiotropic regulatory gene wblA(gh) influences
      morphogenesis and moenomycin production.
AB  - The wblA(gh) gene, encoding a homologue of the WhiB-family of proteins, was
      identified in the sequenced genome of moenomycin producer Streptomyces
      ghanaensis. Deletion of the gene blocked aerial mycelium sporulation and caused a
      230% increase in moenomycins production. S. ghanaensis overexpressing SSFG-01620:
      a homologue of extracellular protease inhibitor SCO0762, whose expression in
      Streptomyces coelicolor is down-regulated by wblA: showed deficiencies in
      sporulation similar to that of wblA(gh) knockout strain. The wblA(gh) gene of S.
      ghanaensis appears to play a negative role in the control of moenomycin
      biosynthesis and is essential for sporulation.

PMID- 21858668
TI  - A novel method for human hematopoietic stem/progenitor cell isolation from
      umbilical cord blood based on immunoaffinity aqueous two-phase partitioning.
AB  - A novel cell separation process based on immunoaffinity aqueous two phase systems
      is presented to isolate and purify CD34(+) stem/progenitor cells directly from
      the whole umbilical cord blood (UCB). A system, composed of polyethylene glycol
      and dextran, was evaluated for the selective recovery of CD34(+) cells from UCB.
      A monoclonal antibody against the CD34 surface antigen was used for the direct
      partitioning of CD34(+) cells in UCB to the PEG-rich phase. The initial
      population of CD34(+) cells (0.2% of the initial sample) was enriched to values
      up to 42% in a single partitioning step, while the majority of contaminant cells
      were partitioned to the dextran-rich phase (1.37 * 10(-2) < K(P) < 2.76 * 10(
      2)). This novel selection method allowed a recovery yield of 95% of CD34(+) cells
      with a purification factor of 245 and is expected to pave a new way to purify
      hematopoietic stem/progenitor cells for use in a variety of clinical settings.

PMID- 21858669
TI  - 2,4,6-Trinitrophenol degradation by Bacillus cereus isolated from a firing range.
AB  - Bacillus cereus strain PU, isolated from soil contaminated with explosive waste,
      tolerated up to 1.3 mM 2,4,6 trinitrophenol (TNP) and utilize it aerobically as
      sole nitrogen and carbon source. Degradation of TNP was accompanied by
      stoichiometric release of 2.1 +/- 0.15 mol nitrite/mol TNP at 539 MUmol/h g dry
      cell wt. Metabolism of TNP was accompanied by transient accumulation of an orange
      red metabolite, hydride meisenheimer complex (H-TNP), indicating a metabolic
      pathway involving complete reductive removal of the nitro group as nitrite.

PMID- 21858670
TI  - The Confucian bioethics of surrogate decision making: its communitarian roots.
AB  - The family is the exemplar community of Chinese society. This essay explores how
      Chinese communitarian norms, expressed in thick commitments to the authority and
      autonomy of the family, are central to contemporary Chinese bioethics. In
      particular, it focuses on the issue of surrogate decision making to illustrate
      the Confucian family-grounded communitarian bioethics. The essay first describes
      the way in which the family, in Chinese bioethics, functions as a whole to
      provide consent for significant medical and surgical interventions when a patient
      has lost decision-making capacity. It is argued that the practice of not having
      an established order for surrogate decision makers (e.g., spouse, children, and
      then parents), as it is done in the United States, reflects the acknowledgment
      that the family as a social reality cannot be reduced to a stereotype of the
      appropriate order of default decision makers. This description of the family as
      being in authority to make surrogate decisions for an incompetent family member
      is enriched by an elaboration of the differences among the concepts of patient
      autonomy, family autonomy, and moral autonomy. The Chinese model, as well as the
      Confucian communitarian life of families, engages a family autonomy that is
      supported by a Confucian understanding of moral autonomy, rather than individual
      autonomy. Finally, the issue of possible conflicts between patient and family
      interests in relation to a patient's past wishes in the Chinese model is
      addressed in light of the role of the physician.

PMID- 21858672
TI  - Re: Nicoll A, Sprenger M. learning lessons from the 2009 pandemic: putting
      infections in their proper place. Eur J Epidemiol 2011; 26:191-194.

PMID- 21858671
TI  - Deep, subsurface microflora after excavation respiration and biomass and its
      potential role in degradation of fossil organic matter.
AB  - Three types of Miocene claystones (amorphous, lamellar, and transitional) were
      aseptically sampled from depths of 30 m and 150 m below the soil surface.
      Respiration of these sediments was measured under conditions that prevented
      inoculation by other microorganisms not indigenous to the claystones in situ.
      Microbial respiration was higher in lamellar than amorphous claystones and was
      not affected by sampling depth. During cultivation, microbial biomass (as
      indicated by PLFA) significantly increased. Microbial biomass after cultivation
      was significantly higher in sediments from 30 m than from 150 m depth. Both
      microbial respiration and biomass increased after glucose addition.

PMID- 21858673
TI  - The relationship between positive psychological attributes and psychological well
      being in persons with HIV/AIDS.
AB  - The relationship between personal psychological attributes and psychological well
      being was assessed among adults with HIV/AIDS. The predictive power of sense of
      coherence, dispositional optimism and perceived competence (PC) on positive
      affect (PA), negative affect (NA) and relative mood (PA-NA) were assessed using
      hierarchical linear regression analysis of two data collections, 2 months apart,
      from 124 HIV-infected participants. In cross-sectional models all of the baseline
      psychological attributes accounted for a significant amount of variance in the
      well-being measures. In longitudinal analyses, changes in PA were predicted by PC
      and dispositional optimism but not by sense of coherence. The positive
      psychological attributes did not predict changes in NA. Sense of coherence,
      dispositional optimism and PC, individually and in composite form, significantly
      correlate with psychological well-being among HIV infected persons. However,
      change in psychological well-being might be best predicted by PC.

PMID- 21858674
TI  - Molecular fractionation and characterization of a Candida albicans fraction that
      increases tumor cell adhesion to hepatic endothelium.
AB  - Systemic candidiasis remains a major complication among patients suffering from
      hematological malignancies and favors the development of hepatic metastasis. To
      contribute to the understanding of the underlying mechanisms, the aim of this
      study was to identify molecules that may increase tumor cell adhesion to hepatic
      endothelial cells. To this end, a well-established in vitro model was used to
      determine the enhancement of tumor cell adhesion induced by Candida albicans and
      its fractions. Different fractions were obtained according to their molecular
      weight (M(r)) (five) or to their isoelectric point (pI) (four), using preparative
      electrophoresis and preparative isoelectric focusing, respectively, followed by
      affinity chromatography. The fraction that most enhanced melanoma cell adhesion
      to endothelium had an M(r) range from 45 to 66 kDa. It was characterized using
      two-dimensional electrophoresis, and 14 proteins were identified by peptide mass
      fingerprinting: Dor14p, Fba1p, Pdi1p, Pgk1p, Idh2p, Mpg1p, Sfa1p, Ape3p, Ilv5p,
      Tuf1p, Act1p, Eno1p, Qcr2p, and Adh1p. Of these, several are related to the
      immunogenic response, and the latter seven belonged to the most reactive fraction
      according to their pI range, from 5 to 5.6. These findings could represent a step
      forward in the search for new targets, to suppress the pro-metastatic effect of
      C. albicans.

PMID- 21858675
TI  - S-methyl thioesters are produced from fatty acids and branched-chain amino acids
      by brevibacteria: focus on L-leucine catabolic pathway and identification of acyl
      CoA intermediates.
AB  - Despite their importance as potent odors that contribute to the aroma of numerous
      cheeses, S-methyl thioesters formation pathways have not been fully established
      yet. In a first part of our work, we demonstrated that Brevibacterium antiquum
      and Brevibacterium aurantiacum could produce S-methyl thioesters using short
      chain fatty acids or branched-chain amino acids as precursors. Then, we focused
      our work on L-leucine catabolism using liquid chromatography tandem mass
      spectrometry and gas chromatography-mass spectrometry analyses coupled with
      tracing experiments. For the first time, several acyl-CoAs intermediates of the L
      leucine to thioesters conversion pathway were identified. S-methyl
      thioisovalerate was produced from L-leucine, indicating that this amino acid was
      initially transaminated. Quite interestingly, data also showed that other S
      methyl thioesters, e.g., S-methyl thioacetate or S-methyl thioisobutyrate, were
      produced from L-leucine. Enzymatic and tracing experiments allowed for
      postulating catabolic pathways leading to S-methyl thioesters biosynthesis.

PMID- 21858676
TI  - Type I IFNs signaling and apoptosis resistance in glioblastoma cells.
AB  - Deletion of type I IFN genes and resistance to apoptosis induced by type I IFNs
      are common in glioblastoma. Here we have investigated the importance of the
      constitutive weak IFN-signaling in the apoptotic response to IFN-alpha in
      glioblastoma cells. U87MG cells hold a deletion of type I IFN genes, whereas in
      T98G cells the spontaneous IFN signaling is intact. In response to IFN-alpha
      U87MG cells produce much less TRAIL, while other IFN-inducible genes were
      efficiently up-regulated. Alterations in TRAIL promoter sequence and activity
      were not observed. DNA methylation can influence TRAIL transcription but without
      overt differences between the two cell lines. We also discovered that TRAIL mRNA
      stability is influenced by IFN-alpha, but again no differences can be appreciated
      between the two cell lines. By silencing IFNAR1 we provide evidences that the
      spontaneous IFN signaling loop is required to sustain elevated levels of TRAIL
      expression, possibly through the regulation of IRF-1. Despite the
      presence/absence of the constitutive IFN signaling, both cell lines were
      resistant to IFN-alpha induced apoptosis. Targeting the deisgylase USP18 can
      overcome resistance to IFN-induced apoptosis only in T98G cells. Alterations in
      elements of the extrinsic apoptotic pathway, such as Bid and c-FLIP contribute to
      apoptotic resistance of U87MG cells. Down-regulation of USP18 expression together
      with the induction of ER-stress efficiently restored apoptosis in U87MG cells.
      Finally, we demonstrated that the BH3-only protein Noxa provides an important
      contribution in the apoptotic response to ER-stress in USP18 silenced cells.

PMID- 21858677
TI  - Nicotine reduces VEGF-secretion and phagocytotic activity in porcine RPE.
AB  - BACKGROUND/PURPOSE: Smoking is a strong environmental factor for the development
      of age-related macula degeneration. In this study, we investigated the effects of
      nicotine on RPE cell function in porcine in vitro models, focussing on cell
      death, VEGF secretion and phagocytotic ability. METHODS: For these experiments,
      perfusion organ culture and primary RPE cell culture were used and exposed to
      nicotine up to 7 days. Survival was investigated in primary porcine RPE cells in
      an MTT and trypan blue exclusion assay. VEGF secretion was investigated in a
      porcine perfusion organ culture model using ELISA. A phagocytosis assay using
      FITC-labelled latex beads in primary RPE cells was used to assess the
      phagocytotic ability of the cells. RESULTS: Nicotine does not induce cell death
      in the RPE at any time point up to 7 days of stimulation at any tested
      concentration. VEGF secretion, however, is diminished compared to untreated
      control already after 1 day of nicotine treatment and even more profoundly up to
      7 days. Furthermore, phagocytotic ability of the RPE is diminished by nicotine in
      the highest concentrations tested (100 MUM). CONCLUSION: Nicotine impedes RPE
      function (VEGF secretion, phagocytosis), which could be directly involved in the
      development of dry AMD and geographic atrophy.

PMID- 21858678
TI  - Randomized crossover study of latanoprost and travoprost in eyes with open-angle
      glaucoma.
AB  - INTRODUCTION: To compare the intraocular pressure (IOP)-lowering effects of
      0.005% latanoprost to that of 0.004% travoprost in eyes with open-angle glaucoma
      (OAG). METHODS: Forty-two patients with OAG who received either latanoprost or
      travoprost every evening for 12 weeks, and then switched to the other medication
      for another 12 weeks. The IOP measurements were made with a Goldmann applanation
      tonometer (GAT) at the baseline, and at 1, 3, 4, and 6 months after the
      treatment. The IOP at the untreated baseline and at the end of each treatment
      period was measured at 10:00, 12:00, and 16:00 hours. The central corneal
      thickness (CCT) was measured at each visit using an ultrasonic pachymeter.
      RESULTS: The mean baseline IOP was 13.9 +/- 2.5 mmHg, and the CCT was 536.7 +/-
      30.5 MUm. Latanoprost reduced the IOP by 2.5 +/- 1.7 mmHg and travoprost by 2.6
      +/- 1.5 mmHg from the baseline (p = 0.6807). The CCT decreased significantly to
      531.9 +/- 30.3 at 3 months (p = 0.0160) and to 529.4 +/- 30.5 MUm at 6 months (p
      = 0.0002) after the therapy. The decrease was significantly greater in eyes after
      travoprost (p = 0.0049). CONCLUSIONS: Travoprost has similar effect as
      latanoprost in reducing the IOP in glaucoma patients with relatively low IOPs.
      The use of prostaglandin analogs can decrease the CCT, and this change should be
      considered when the IOPs obtained by GAT are analyzed.

PMID- 21858679
TI  - Visual signals bias auditory targets in azimuth and depth.
AB  - In the psychophysical phenomenon visual bias, an accurately localized irrelevant
      signal, such as a light, impairs localization of a spatially discrepant target,
      such as a sound, when the two stimuli are perceived as unified. Many studies have
      demonstrated visual bias in azimuth, but none have tested directly or found this
      effect in depth. The current study was able to produce over 90% bias in azimuth
      and somewhat less (83%) bias in depth. A maximum likelihood estimate can predict
      bias by the variance in the localization of each unimodal signal in each
      dimension in space.

PMID- 21858682
TI  - Involvement of ecto-5'-nucleotidase/CD73 in U138MG glioma cell adhesion.
AB  - Glioblastoma multiform is the most common and aggressive type of brain tumor. The
      overexpression of ecto-5'-nucleotidase/CD73 (ecto-5'-NT/CD73), an adhesion
      molecule and the main enzymatic source of extracellular adenosine, has been
      reported in tumor cells, and it is emerging as a component of glioma progression.
      Here, we evaluated the involvement of ecto-5'-NT/CD73 in cell adhesion through
      its interaction with different components of the extracellular matrix in the
      human U138MG glioma cell line. The results indicated that adenosine induced an
      increase in glioma cell adhesion. The treatment of glioma cells with adenosine
      receptor antagonists, APCP (alpha,beta-methylene ADP) and dipyridamole prevented
      the adenosine effect, indicating the participation of extracellular and
      intracellular signaling pathways in cell adhesion mediated by adenosine. The ECM
      protein laminin (lam) and chondroitin sulfate (ChS) modulated the ecto-5'-NT/CD73
      activity and glioma adhesion in a parallel manner, suggesting the involvement of
      purinergic signaling in the effects mediated by the extracellular matrix. Taken
      together, these results suggest that ecto-5'-NT/CD73, an important producer of
      extracellular adenosine, may modulate glioma cell adhesion and tumor cell
      extracellular matrix interactions.

PMID- 21858680
TI  - Initiation of segmental locomotor-like activities by stimulation of ventrolateral
      funiculus in the neonatal rat.
AB  - Descending control is critically important for the generation of locomotor
      activities. Yet, our understanding of the descending control system of locomotion
      is limited. We hypothesized that stimulation of the ventrolateral funiculus (VLF)
      induces rhythmic activity in lumbar neurons that is correlated with locomotor
      like activity in the neonatal rat. Intracellular recordings were conducted in the
      L2-L3 lumbar segments, while locomotor-like output was monitored in the L2 and L5
      ventral roots. Stimulation of the VLF at thoracic segments induced locomotor-like
      activity in the L2 and L5 ventral roots in majority of the preparations (26/33).
      In a few midline split cord preparations (4/13), VLF stimulation induced rhythmic
      locomotor-like bursts in either L2 or L5 ventral root without alternating pattern
      between the ventral roots. The response latencies suggest that VLF stimulation
      induced antidromic activation (<1 ms, 8 cells), monosynaptic activation (1-3 ms,
      18 cells), and oligosynaptic activation (3.5-5 ms, 14 cells) of segmental neurons
      in the lumbar region. VLF stimulation induced rhythmic membrane potential
      oscillations with or without bursting of action potentials in 9 of 40 putative
      interneurons. The membrane potential oscillations were in phase with the
      locomotor-like output of the L2 ventral root in 7 of the 9 cells while the other
      2 cells oscillated in phase with the L5 ventral root activity. We have thus
      demonstrated that descending axons exist in the VLF which make synaptic
      connections with segmental neurons in the lumbar region that may be a critical
      element of the locomotor neural network for the initiation of locomotion.

PMID- 21858683
TI  - Continuous spinal drain following endoscopic third ventriculostomy: a proposal to
      change the definition of failure.
AB  - PURPOSE: This study evaluates the safety, efficacy, and indications for
      continuous lumbar drainage (CLD) in patients following endoscopic third
      ventriculostomy (ETV). METHODS AND RESULTS: We retrospectively reviewed the
      clinical data of 22 consecutive patients treated between 1996 and 2010 with CLD
      after ETV. The decision to insert a CLD was made in selected patients only. CLD
      was inserted in cases of high measured intracranial pressure (12 patients),
      clinical symptoms indicative of continuing hydrocephalus (2 patients), and
      "prophylactically" in 8 patients, based either on the clinical condition of
      patients before ETV or on technical difficulties during the ETV procedure, which
      seemed to increase the risk of ETV failure. CLD insertion took place either in
      the operating room immediately following the ETV procedure or under very specific
      conditions and with close patient monitoring in an ICU setting. Only four
      patients eventually required shunting, all within 1 month after ETV. Therefore,
      the overall ETV success rate was 81.8% (18/22 patients). Of the 14 patients
      suffering from measured or clinically observed continuing hydrocephalus, 12 (85%)
      ultimately recovered without the need for a permanent shunt. Without the CLD,
      some of these patients would probably have been declared "failures" and referred
      for a standard shunt. CLD provided a time window following ETV for the absorption
      system to recover and return to full functionality. CONCLUSIONS: Selective usage
      of CLD is a reasonable and safe method to gain time and possibly facilitates the
      recovery of absorption capacity following ETV. CLD should be considered before
      conceding a post-ETV patient as a failure.

PMID- 21858684
TI  - Three dimensional-CT evaluation of femoral neck anteversion, acetabular
      anteversion and combined anteversion in unilateral DDH in an early walking age
      group.
AB  - PURPOSE: At present, the indications for femoral derotational osteotomy remain
      controversial due to the inconsistent findings in femoral neck anteversion in
      developmental dysplasia of the hip (DDH). Moreover, combined anteversion is not
      assessed in unilateral DDH using three dimensional-CT. Therefore, the purposes of
      our study were to observe whether the femoral neck anteversion (FA), acetabular
      anteversion (AA) and combined anteversion (CA) on the dislocated hips were
      universally presented in unilateral DDH according to the classification system of
      Tonnis. METHODS: Sixty-two patients with unilateral dislocation of hip were
      involved in the study, including 54 females and eight males with a mean age of
      21.63 months (range, 18-48 months). The FA, AA and CA were measured and compared
      between the dislocated hips and the unaffected hips. RESULTS: Although no
      significant difference was observed in FA between the dislocated hips and the
      unaffected hips (P = 0.067, 0.132, respectively) in Tonnis II and III type, FA
      was obviously increased on the dislocated hips compared with the unaffected hips
      in Tonnis IV type. Increased AA on the dislocated hips was a universal finding in
      Tonnis II, III and IV types. Meanwhile, a wide safe range of CA from 24 degrees 
      to 62 degrees  was demonstrated on the unaffected hips. CONCLUSION: Femoral
      derotational osteotomy seems not to be necessary in Tonnis II and III types in
      unilateral DDH. Femoral derotational osteotomy should be considered in DDH,
      especially in Tonnis IV type, if the CA is still above 62 degrees  and the hip
      joints present instability in operation after abnormal acetabular anteversion,
      acetabular index and acetabular coverage of the femoral head are recovered to
      normal range through pelvic osteotomy.

PMID- 21858686
TI  - The interaction graph structure of mass-action reaction networks.
AB  - Behaviour of chemical networks that are described by systems of ordinary
      differential equations can be analysed via the associated graph structures. This
      paper deals with observations based on the interaction graph which is defined by
      the signs of the Jacobian matrix entries. Some of the important graph structures
      linked to network dynamics are signed circuits and the nucleus (or Hamiltonian
      hooping). We use mass-action chemical reaction networks as an example to showcase
      interesting observations about the aforementioned interaction graph structures.
      We show that positive circuits and specific nucleus structures (associated to
      multistationarity) are always present in a great generic class of mass-action
      chemical and biological networks. The theory of negative circuits remains poorly
      understood, but there is some evidence that they are indicators of stable
      periodicity. Here we introduce the concept of non-isolated circuits which
      indicate the presence of a negative circuit.

PMID- 21858685
TI  - Chiral ruthenium(II) anthraquinone complexes as dual inhibitors of topoisomerases
      I and II.
AB  - DNA topoisomerases (I and II) have been one of the excellent targets in
      anticancer drug development. Here two chiral ruthenium(II) anthraquinone
      complexes, Delta- and Lambda-[Ru(bpy)(2)(ipad)](2+), where bpy is 2,2'-bipyridine
      and ipad is 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline,
      were synthesized and characterized. As expected, both of the Ru(II) complexes
      intercalate into DNA base pairs and possess an obviously greater affinity with
      DNA. Topoisomerase inhibition and DNA strand passage assay confirmed that the two
      complexes are efficient dual inhibitors of topoisomerases I and II by
      interference with the DNA religation. In MTT cytotoxicity studies, two Ru(II)
      complexes exhibited antitumor activity against HeLa, MCF-7, HepG2 and BEL-7402
      tumor cell lines. Flow cytometry analysis shows an increase in the percentage of
      cells with apoptotic morphological features in the sub-G1 phase for Ru(II)
      complexes. Nuclear chromatin cleavage has also been observed from AO/EB staining
      assay and alkaline single-cell gel electrophoresis (comet assay). The results
      demonstrated that Delta- and Lambda-[Ru(bpy)(2)(ipad)](2+) act as dual inhibitors
      of topoisomerases I and II, and cause DNA damage that can lead to cell cycle
      arrest and/or cell death by apoptosis.

PMID- 21858687
TI  - Reaction-diffusion model of atherosclerosis development.
AB  - Atherosclerosis begins as an inflammation in blood vessel walls (intima). The
      inflammatory response of the organism leads to the recruitment of monocytes.
      Trapped in the intima, they differentiate into macrophages and foam cells leading
      to the production of inflammatory cytokines and further recruitment of white
      blood cells. This self-accelerating process, strongly influenced by low-density
      lipoproteins (cholesterol), results in a dramatic increase of the width of blood
      vessel walls, formation of an atherosclerotic plaque and, possibly, of its
      rupture. We suggest a 2D mathematical model of the initiation and development of
      atherosclerosis which takes into account the concentration of blood cells inside
      the intima and of pro- and anti-inflammatory cytokines. The model represents a
      reaction-diffusion system in a strip with nonlinear boundary conditions which
      describe the recruitment of monocytes as a function of the concentration of
      inflammatory cytokines. We prove the existence of travelling waves described by
      this system and confirm our previous results which suggest that atherosclerosis
      develops as a reaction-diffusion wave. The theoretical results are confirmed by
      the results of numerical simulations.

PMID- 21858688
TI  - Optimal cut-off values of anthropometric markers to predict hypertension in North
      Indian population.
AB  - The aim of the study was to determine the cut-offs of anthropometric markers for
      detecting hypertension in an endogamous North Indian population. A cross
      sectional study was carried out to collect data from 578 adult Aggarwal Baniya
      subjects (271 men and 307 women, mean age: 43.4 +/- 5.3 and 38.7 +/- 4.9
      respectively) using multistage, stratified sampling method. Individual body
      weight, height, waist circumference (WC), hip circumference, blood pressure were
      assessed. Receiver operating characteristic (ROC) analysis was used to find out
      the optimal cut-off values of various anthropometric markers to predict
      hypertension. The likelihood ratios for having hypertension in subjects with
      various cut-off values were calculated. Logistic regression analysis was used to
      examine the independent relationship between the anthropometric markers and odds
      of having hypertension. The BMI cut-off to predict hypertension was 22.8 kg/m(2)
      in men and 28.8 kg/m(2) in women. The optimal WC cut-offs varied from 91-92 cm in
      both men and women. The WHR cut-off was about 0.90 in men and 0.78 in women
      respectively, and the optimal WHtR cut-off was 0.56 in men and 0.43 in women. The
      cut-off levels for BMI, WC and WHtR corresponded to the inflexion points in the
      likelihood ratio graphs. The area under curve (AUC) and odds ratios showed that
      the risk of having hypertension was highest with respect to increased BMI and
      that BMI is the best predictor of having hypertension. The cut-off points for
      detecting cardiovascular risk factors among our population are lower than the
      criteria by the World Health Organization. Although these results may not be
      readily applied to the rest of the Indian populations due to the multiethnic
      composition, they point to the necessity of similar studies with large randomized
      samples to find the cut-off levels for chronic conditions in different
      populations.

PMID- 21858690
TI  - Changing urbanization patterns in US lung cancer mortality, 1950-2007.
AB  - This study examined disparities in lung cancer mortality rates among US men and
      women in metropolitan and non-metropolitan areas from 1950 through 2007. Annual
      age-adjusted mortality rates were calculated for men and women in metropolitan
      and non-metropolitan areas, and differences in mortality rates were tested for
      statistical significance. Log-linear regression was used to model annual rates of
      change in mortality over time, while Poisson regression was used to estimate
      relative risk after adjusting for age, sex, deprivation, and urbanization levels.
      Urbanization patterns in lung cancer mortality changed dramatically between 1950
      and 2007. Compared to men in metropolitan areas, men aged 25-64 years in non
      metropolitan areas had significantly lower lung cancer mortality rates from 1950
      to 1977 and men aged >=65 years in non-metropolitan areas had lower mortality
      rates from 1950 to 1985. Differentials began to reverse and widen by the mid
      1980s for men and by the mid-1990s for younger women. In 2007, compared to their
      metropolitan counterparts, men aged 25-64 and >=65 years in non-metropolitan
      areas had 49 and 19% higher lung cancer mortality and women aged 25-64 and >=65
      years in non-metropolitan areas had 32 and 4% higher lung cancer mortality,
      respectively. Although adjustment for deprivation levels reduced excess lung
      cancer mortality risk among those in non-metropolitan areas, significant rural
      urban differences remained. Rural-urban patterns reversed because of faster and
      earlier reductions in lung cancer mortality among men and women in metropolitan
      areas. Temporal trends in rural-urban disparities in lung cancer mortality appear
      to be consistent with those in smoking.

PMID- 21858689
TI  - Physical activity among Amish and non-Amish adults living in Ohio Appalachia.
AB  - To understand the behavioral lifestyle factors that may contribute to lower
      cancer incidence rates among the Amish population, this study evaluated
      differences in physical activity (PA) levels between Amish and non-Amish adults
      living in Ohio Appalachia. Amish (n = 134) and non-Amish (n = 154) adults
      completed face-to-face interviews as part of a cancer-related lifestyle study.
      Self-report of PA level was measured by the International Physical Activity
      Questionnaire (IPAQ) and by a diary of steps/day (pedometer: Digi-Walker SW-200).
      Total metabolic equivalent tasks (MET) minutes was calculated from the IPAQ and
      average number of steps/day from a pedometer diary. Amish males walked more
      steps/day (mean +/- standard error (SE): 11,447 +/- 611 vs. 7,605 +/- 643; P <
      0.001) and had a higher IPAQ score (MET min/week) (mean +/- SE: 8,354 +/- 701 vs.
      5,547 +/- 690; P < 0.01) than non-Amish males. In addition, Amish farmers walked
      significantly more steps/day than Amish non-farmers (mean +/- SE: 15,278 +/-
      1,297 vs. 10,742 +/- 671; P < 0.01). There was a trend for Amish females to walk
      more steps/day (mean +/- SE: 7,750 +/- 477 vs. 6,547 +/- 437; P = 0.06) and to
      have higher IPAQ scores (mean +/- SE: 4,966 +/- 503 vs. 3,702 +/- 450; P = 0.06)
      compared to non-Amish females. Two measures of PA demonstrated a higher PA level
      among Amish males, especially farmers, and a trend for higher PA level among
      Amish females. Higher levels of PA warrants further investigation as one factor
      potentially contributing to lower cancer incidence rates documented among the
      Amish.

PMID- 21858691
TI  - Mechanical behavior of human embryonic stem cell pellet under unconfined
      compression.
AB  - As a prelude to the understanding of mechanotransduction in human embryonic stem
      cell (hESC) differentiation, the mechanical behavior of hESCs in the form of cell
      pellet is studied. The pellets were tested after 3 or 5 weeks of cell culture in
      order to demonstrate the effect of the duration of cell culture on the mechanical
      properties of the pellets. A micromechanical tester was used to conduct
      unconfined compression on hESC pellet, and experimental, numerical, and
      analytical methods were combined to determine the mechanical properties of hESC
      pellet. It is assumed that the mechanical behavior of hESC pellets can be
      described by an isotropic, linear viscoelastic model consisting of a spring and
      two Maxwell units in parallel, and the Poisson's ratio of the hESC pellet is
      constant based on pellet deformation in the direction perpendicular to the
      compression direction. Finite element method (FEM) simulation was adopted to
      determine the values of Poisson's ratio and the five parameters contained in the
      viscoelastic model. The variations of Poisson's ratio and the initial elastic
      modulus are found to be larger compared with those of the four other parameters.
      Results show that longer duration of cell culture leads to higher modulus of hESC
      pellet. The effect of pellet size error on the values of mechanical parameters
      determined is studied using FEM simulation, and it is found that the effect of
      size error on Poisson's ratio and initial elastic modulus is much larger than
      that on the other parameters.

PMID- 21858692
TI  - Optimal time for passaging neurospheres based on primary neural stem cell
      cultures.
AB  - Cultured neural stem cells (NSCs) provide a powerful means for investigating
      central nervous system disease, neuron development, differentiation, and
      regeneration. To obtain sufficient neurospheres, subculturing is essential
      following establishment of the primary NSC culture. Passaging the primary
      neurospheres is a key issue that is often ignored. We evaluated the influence of
      different passaging schedules on primary cultured NSCs. Passaging was performed
      on day 5, 7 or 9. We observed more neurospheres with diameters of 200-250 MUm on
      day 7 than on day 5 or 9. Prolonging the time of primary culture reduced the cell
      metabolic activity by the MTT assay and cell proliferation by colony-forming
      assay and the differentiation to neurons from cells at P2 and later decreased.
      Additionally, more cells were in G0/G1 phase, and higher expression of p16 (
      INK4a ) and lower expression of cyclin D1 was found when the time of primary
      culture was prolonged to 9 days compared to 7-days cultures. Thus, in this study,
      we established that the optimal time for subculturing aggregated NSCs was on day
      7 based on the primary culture.

PMID- 21858693
TI  - Interface of data transmission for a transcutaneous communication system using
      the human body as transmission medium.
AB  - We have been developing a new transcutaneous communication system (TCS) that uses
      the human body as an electrical conductive medium. We studied an interface
      circuit of the TCS in order to optimize the  leading data current into the human
      body effectively. Two types of LC circuits were examined for the interface
      circuit, one was an LC series-parallel circuit, and the other was a parallel
      connected LC circuit. The LC series-parallel circuit connected to the body could
      be tuned to a resonant frequency, and the frequency was determined by the values
      of an external inductor and an external capacitor. Permittivity of the body did
      not influence the electrical resonance. Connection of the LC series-parallel
      circuit to the body degraded the quality factor Q because of the conductivity of
      the body. However, the LC parallel-connected circuit when connected to the body
      did not indicate electrical resonance. The LC series-parallel circuit restricts a
      direct current and a low-frequency current to flow into the body; thus, it can
      prevent a patient from getting a shock. According to the above results, an LC
      series-parallel circuit is an optimum interface circuit between the TCS and the
      body for leading data current into the body effectively and safely.

PMID- 21858694
TI  - Molecular cloning, sequence characterization, and tissue expression analysis of
      Hi-Line Brown chicken Akirin2.
AB  - Akirins are novel important nuclear proteins able to modulate transcriptional
      activities in a gene-specific manner. Akirin2 is an important gene related to
      immune responses, it is necessary to isolate the akirin2 gene from chicken
      because it may be associated with vaccine and enhancement of immune response. In
      this study, a Hi-Line Brown chicken homolog of the vertebrate akirin2 gene was
      cloned, sequenced, and characterized. The akirin2 full-length coding sequence
      (CDS) consisted of 576nt and encoded 191 amino acids with a molecular weight of
      21.58 kD. The COOH-terminal alpha-helix region was well conserved between chicken
      and other animals. RT-PCR analysis showed that the akirin2 transcripts were
      constitutively expressed in 16 tissues tested. Several microRNA target sites were
      predicted in the CDS of chicken akirin2 gene. We presume that Akirin2 protein may
      be used as a new-type immunopotentiator in poultry immune system in the future.

PMID- 21858695
TI  - Rapid identification and detection of intracellular survival testing of
      mycobacterium smegmatis mc2155 that contains eis gene from mycobacterium
      tuberculosis by flow cytometry.
AB  - Mycobacterium tuberculosis is a facultative intracellular pathogen that has
      evolved the ability to survive and multiply within human macrophages. The
      enhanced intracellular survival (eis) gene (Rv2416c) from M. tuberculosis has
      been identified as a potential factor that can enhance the intracellular survival
      of Mycobacterium smegmatis in the macrophage cell line. However, the time
      requirements for intracellular survival testing of Mycobacterium using classical
      methodologies are still too long. In this study, we used M. smegmatis mc2155 that
      contains eis to develop and study a rapid method to test intracellular survival
      using flow cytometry. We demonstrated the success of this technique, which
      required only a few hours. This assay is rapid, accurate, and reproducible, and
      it would be valuable for the rapid detection of intracellular survival of
      mycobacteria.

PMID- 21858696
TI  - Cloning, characterization and diversity of insecticidal crystal protein genes of
      bacillus thuringiensis native isolates from soils of Andaman and Nicobar Islands.
AB  - Bt strains were isolated from soils of Andaman and Nicobar Islands and
      characterized by microscopic and molecular methods. Diversity was observed both
      in protein and cry gene profiles, where majority of the isolates showed presence
      of 65 kDa protein band on SDS-PAGE while rest of them showed 130, 72, 44, and 29
      kDa bands. PCR analysis revealed predominance of cry1I and cry7, 8 genes in these
      isolates. The PCR screening strategy presented here led us to identify putative
      novel cry genes which could be active against Coleoptera insects. Variation in
      the nucleotide sequences of cry genes from the isolates suggests that the genetic
      diversity of Bt isolates results from the influence of different ecological
      factors and spatial separation between strains generated by the conquest of
      different habitats in the soils of Andaman and Nicobar islands. The implications
      of our studies are important from the point of view of identifying novel cry
      genes that could be toxic to insects other than lepidoptera.

PMID- 21858697
TI  - Davallialactone protects against adriamycin-induced cardiotoxicity in vitro and
      in vivo.
AB  - Adriamycin (ADR) is a potent anticancer drug. Its clinical applications are
      limited due to its cardiotoxicity. Oxidative stress is responsible for
      cardiomyopathy induced by ADR. Previous studies have demonstrated that
      davallialactone (DAVA), extracted from mushroom Inonotus xeranticus, has
      potential antiplatelet aggregation activity and free radical scavenging
      properties. In this study, we investigated whether DAVA has protective effects
      against ADR-induced free radical accumulation and apoptosis in cardiac muscle
      cells and compared the effects of DAVA with N-acetylcysteine, a potent
      antioxidant. We evaluated the effect of DAVA on ADR-induced cytotoxicity by MTT
      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and crystal
      violet staining, the reactive oxygen species (ROS) production by flow cytometry,
      and the expression of stress-related proteins like Cu/Zn superoxide dismutase
      (SOD), Mn-SOD, and the involvement of mitogen-activated protein kinase pathway by
      Western blot analysis. Apoptosis was assessed by nuclear condensation and the
      expression levels of pro-apoptotic proteins, such as caspase-3 and polyadenosine
      diphosphate-ribose polymerase (PARP). The cardio-protective effects of DAVA were
      also evaluated in an in vivo study in an animal model of ADR-induced acute
      cardiomyopathy. Our results showed that DAVA significantly increased the
      viability of doxorubicin-injured H9c2 cells and inhibited ADR-induced ROS
      production, apoptosis, and the expression of Cu/Zn SOD and Mn-SOD. DAVA also
      inhibited the expression of extracellular signal-regulated kinase (ERK) and c-Jun
      N-terminal kinase (JNK), which was activated by ADR. In the in vivo animal model,
      treatment involving DAVA significantly reduced cardiomyocyte lesions. These
      results suggest that DAVA is a potentially protective agent for ADR-induced
      cardiotoxicity in cardiomyocytes and can be a potential candidate to protect
      against cardiotoxicity in ADR-treated cancer patients.

PMID- 21858698
TI  - Effect of phenolic compounds against Abeta aggregation and Abeta-induced toxicity
      in transgenic C. elegans.
AB  - Substantial evidence suggests that the aggregation of amyloid-beta (Abeta)
      peptide into fibrillar structures that is rich in beta-sheets is implicated as
      the cause of Alzheimer's disease. Therefore, an attractive therapeutic strategy
      is to prevent or alter Abeta aggregation. Phenolic compounds are natural
      substances that are composed of one or more aromatic phenolic rings and present
      in wine, tea, fruits, vegetables and a wide variety of plants. In this work, we
      investigated the effects of ferulic acid, morin, quercetin and gossypol against
      Abeta aggregation. From the ThT and turbidity assays, it is observed that in
      addition to the fibril aggregate, another type of aggregate is formed in the
      presence of morin, quercetin, and gossypol. On the other hand, ferulic acid did
      not prevent fibril formation, but it did appear to reduce the average length of
      fibrils compared to Abeta alone. To study the protective effects of phenolic
      compounds on Abeta-induced toxicity, we utilized the nematode Caenorhabditis
      elegans (C. elegans) as an in vivo model organism, human Abeta is expressed
      intracellularly in the body wall muscle. We found that exposure of Caenorhabditis
      elegans to ferulic acid give more protection against Abeta toxicity than morin,
      quercetin and gossypol.

PMID- 21858699
TI  - Hydrolysis of substance P in the presence of the osteosarcoma cell line SaOS-2:
      release of free amino acids.
AB  - The possible hydrolysis of substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu
      Met) in presence of the osteoblastic cell line SaOS-2 was measured by capillary
      electrophoresis coupled to mass detection. The results obtained indicate that a
      very rapid disappearance of the intact undecapeptide was associated to a slower
      appearance of seven of its eight component amino acids. These results can be
      interpreted as indicating that an extremely fast hydrolysis of substance P by
      endopeptidases, which released peptidic by-products, was followed by a noticeably
      slower secondary degradation which released free amino acids. In decreasing
      quantitative importance, these phenomena appear to originate by the hydrolysis of
      the Pro(4)-Gln(5) bond, followed by C-terminal sequential degradation of the
      Arg(1)-Pro(4) tetrapeptide; by the hydrolysis of or Phe(7)-Phe(8) bond (or,
      possibly, of Gln(6)-Phe(7)) leading to release of free Phe and Gln; by hydrolysis
      of the Gly(9)-Leu(10) bond with subsequent release of Met and Leu. Results
      obtained appear to be compatible with the expression by SaOS-2 cells of enzymes
      already known to catalyze substance P hydrolysis, together with an apparent low
      efficiency of aminopeptidases. Because of the activity of C-terminal fragments on
      NK1 receptors, the delay between primary hydrolysis of substance P and secondary
      hydrolysis of its peptidic fragments indicated by the data shown implies a
      possible persistence of substance P physiological effects even after degradation
      of the intact peptide.

PMID- 21858700
TI  - Attentional modulation of early ERP components in response to faces: evidence
      from the attentional blink paradigm.
AB  - The attentional blink (AB) is a transient attentional deficit that occurs when
      two stimuli that must both be detected are presented within an interval of less
      than 500 ms. Event-related potential (ERP) investigations have suggested that the
      AB affects a specific component, the P3, which is suppressed when targets are
      blinked. In view of the link between the P3 and working memory, it has been
      suggested that the AB might be due to the inability of the blinked target to
      access working memory. Interestingly, it seems that faces, due to their saliency,
      might escape the AB effect when cross-category detection is required (i.e., when
      the targets are composed of faces versus other categories of stimuli). In the
      present study we investigated this phenomenon in an event-related potential (ERP)
      study using upright and inverted faces as targets. In a first task, the
      participants were asked to identify two successive targets, the first composed of
      geometric shapes and the second of upright or inverted faces. A second control
      task, identical to the first was also performed, in which only the second targets
      had to be identified in order to compare ERPs. ERPs and scalp topographies of
      physically identical sequences of events, differing only by the attentional
      involvement, were thus compared. Behavioural results showed that faces indeed
      escape the AB while inverted faces do not. However, the electrophysiological
      findings showed that when attention was engaged in a previous stimulus (at the
      shortest lag times), both upright and inverted faces showed a decreased amplitude
      in the 150-260 ms time period, in addition to a lower P3. At longer lags, when
      the AB was no longer observed, no ERP differences were found. Our data
      demonstrate that, although faces escape the attentional blink, previous
      attentional involvement occurs much earlier than described for other categories
      of stimuli. This suggests that faces are subjected to an early selection which
      might allow rapid re-allocation of attention to the stimulus if it is deemed
      meaningful.

PMID- 21858701
TI  - Uncommon co-occurrence of ileal atresia and total colonic aganglionosis in two
      unrelated newborns.
AB  - We report two recent cases of distal ileal atresia associated with total colonic
      aganglionosis (TCA). It is well known that ileal atresia and Hirschsprung's
      disease (HD) are individually frequent causes of intestinal obstruction. However,
      the association of both these diseases is an extremely rare event. To our
      knowledge, only 19 cases of ileal atresia associated with HD have been described
      so far. When a child is diagnosed having ileal atresia, the possibility of
      associated TCA should be considered. Therefore, intra-operative staged biopsies
      should be sent for histological examination in order to rule out or confirm this
      very rare co-occurrence.

PMID- 21858702
TI  - The effect of cyclic anaerobic-aerobic conditions on biodegradation of azo dyes.
AB  - The effect of cyclic anaerobic-aerobic conditions on the biodegradative
      capability of the mixed microbial culture for the azo dye Remazol Brilliant
      Violet 5R (RBV-5R) was investigated in the sequencing batch reactor (SBR) fed
      with a synthetic textile wastewater. The SBR had a 12-h cycle time with anaerobic
      aerobic periods of 3/9, 6/6 and 9/3 h. General SBR performance was assessed by
      measurement of catabolic enzymes (catechol 2,3-dioxygenase, azo reductase),
      chemical oxygen demand (COD), color and amount of aromatic amines. In this study,
      under steady-state conditions, the anaerobic period of the cyclic SBR was found
      to allow the reductive decolorization of azo dye. Longer anaerobic periods
      resulted in higher color removal efficiencies, approximately 71% for the 3-h, 87%
      for 6-h and 92% for the 9-h duration. Total COD removal efficiencies were over
      84% under each of the cyclic conditions and increased as the length of the
      anaerobic period was increased; however, the highest color removal rate was
      attained for the cycle with the shortest anaerobic period of 3 h. During the
      decolorization of RBV-5R, two sulfonated aromatic amines (benzene based and
      naphthalene based) were formed. Additionally, anaerobic azo reductase enzyme was
      found to be positively affected with the increasing duration of the anaerobic
      period; however; it was vice versa for the aerobic catechol 2,3-dioxygenase
      (C23DO) enzyme.

PMID- 21858703
TI  - Simultaneous determination of flubendiamide its metabolite desiodo flubendiamide
      residues in cabbage, tomato and pigeon pea by HPLC.
AB  - A sensitive and simple method for simultaneous analysis of flubendiamide and its
      metabolite desiodo flubendiamide in cabbage, tomato and pigeon pea has been
      developed. The residues were extracted with QuEChERS method followed by
      dispersive solid-phase extraction with primary secondary amine sorbent to remove
      co extractives, prior to analysis by HPLC coupled with UV-Vis detector. The
      recoveries of flubendiamide and desiodo flubendiamide were ranged from 85.1 to
      98.5% and 85.9 to 97.1% respectively with relative standard deviations (RSD) less
      than 5% and sensitivity of 0.01 MUg g(-1). The method offers a less expensive and
      safer alternative to the existing residue analysis methods for vegetables.

PMID- 21858704
TI  - Lead, zinc, and cadmium in vegetable/crops in a zinc smelting region and its
      potential human toxicity.
AB  - Lead, Zn, and Cd in vegetables/crops were investigated in a zinc smelting region
      in China, and their daily dietary intake by local residents was estimated. It is
      observed that Pb, Zn, and Cd were in 34.7-91.1, 242-575, and 0.199-2.23 MUg g(-1)
      dry weight in vegetables/crops with their greatest concentrations in leafy
      vegetable. The daily dietary intake of Pb, Zn, and Cd by adult residents reached
      3, 646, 59,295, and 186 MUg day, respectively, and lettuce and cabbage together
      contributed 75% of the Pb, 50% of the Zn, and 70% of the Cd.

PMID- 21858705
TI  - Organochlorine pesticides in muscle of wild seabass and Chinese prawn from the
      Bohai Sea and Yellow Sea, China.
AB  - Muscle samples from wild seabass and Chinese prawn collected from the Bohai Sea
      and the Yellow Sea, China were analyzed for 22 organochlorine pesticides. DDTs
      were the predominant contaminants in all samples. The concentration of DDTs in
      seabass was 247 MUg kg(-1) wet wt (from 4.30 to 2,089 MUg kg(-1) wet wt).
      Significantly, concentration of DDTs in seabass was much higher than that in
      prawn (6.51 MUg kg(-1) wet wt). Very high concentrations of DDTs and high
      DDT/DDTs ratio were found in seabass samples from some locations, which imply
      there might be new inputs of DDT into the marine environment.

PMID- 21858706
TI  - Assessment of polychlorinated biphenyls contamination in sediment and organism
      from Xiamen offshore area, China.
AB  - In Xiamen offshore area, sediment polychlorinated biphenyls (PCBs) concentrations
      ranged from 2.33 to 30.94 ng/g, with an average value of 8.94 ng/g. The in situ
      organic carbon normalized partition coefficients (log K'(oc)) of the 12 co-polar
      congeners PCBs between sediments and porewater were from 1.50 to 2.64, and the
      log K'(oc) decreased with increasing chlorine number. PCB congeners pattern of
      marine organism were characterized by 5-6 CB chlorinated compounds, and the world
      health organization total dioxin equivalents of PCBs in organism ranged from 1.45
      to 88.26 pg/g lipid.

PMID- 21858707
TI  - Ecotoxicological assessment of cobalt used as supplement in the diet of common
      carp Cyprinus carpio.
AB  - Experiments were performed in the laboratory to determine if excess levels of Co
      used as dietary supplement (0.0, 0.05, 0.10 and 1.0%) to enhance growth of the
      fish Cyprinus carpio was safe for aquatic organisms. Lethal concentrations of Co
      for tadpole of toad Bufo melanostictus (96 h LC(50), 17.2 mg/L), oligochaet worm
      Branchiura sowerbyi (96 h LC(50), 179 mg/L) and crustacean zooplankton Diaptomus
      forbesi (96 h LC(50), 1.5 mg/L) were compared with the concentration of Co in the
      medium leached from the unused diets and faeces. The results indicated that the
      Co leached from diet containing 1.0% Co was ecotoxicologically unsafe for
      crustacean zooplankton.

PMID- 21858708
TI  - Bioaccumulation of heavy metals in freshwater fish species, Anzali, Iran.
AB  - The main objectives of study were to monitor the metals concentrations, in
      freshwater fish species, Carassius gibelio and Esox lucius; and to identify any
      relationships between species and bioaccumulation of metals. The highest
      concentration of metals (cadmium, 1.96; copper, 24.2; zinc, 49.6; lead, 5.4;
      chromium, 4.4) between the fish species and tissues was in the liver of Esox
      lucius, while the lowest (cadmium,0.21; copper,7.2; zinc,19.4; lead,0.9;
      chromium,0.6 MUg/g) found in the muscle of Carassius gibelio. Results showed that
      the metal concentrations were in fishes in descending order of zinc > copper >
      lead > chromium > cadmium, similarly in the tissue liver > kidney > gill ~
      intestine > muscle.

PMID- 21858709
TI  - Influence of the vascular damaging agents DMXAA and ZD6126 on hypericin
      distribution and accumulation in RIF-1 tumors.
AB  - PURPOSE: We investigated the influence of two types of vascular damaging agents
      (VDAs) (DMXAA vs. ZD6126) and sequence of administration (VDA 24 h before HYP vs.
      HYP 1 h before VDA) to evaluate the effect on hypericin (HYP) accumulation and
      distribution in necrotic tumors. METHODS: Frozen sections of dorsally inoculated
      RIF-1 tumors were analyzed by fluorescence microscopy and H&E stained for
      histological evaluation. The localization of HYP was assessed both qualitatively
      and semi-quantitatively in necrotic tumor, viable tumor, or nontarget host
      tissue. RESULTS: Whereas the type of VDA did not influence HYP accumulation and
      distribution, a clear advantage could be seen when administering VDA 24 h before
      HYP compared to HYP 1 h before VDA, pointing toward the absence of a "trapping"
      mechanism. In DMXAA-treated and not in ZD6126-treated tumors, spotty fluorescence
      was observed which is likely to be a consequence of neutrophil phagocytosis.
      Dexamethasone treatment neither did influence this phenomenon nor did change HYP
      uptake in necrotic tumor. CONCLUSIONS: We conclude that HYP accumulation is
      optimal when it is administered after VDA injection. We also found that HYP
      accumulation in necrosis is not changed when using VDAs with different working
      mechanisms. This insight provides a rationale for tumor necrosis therapy (TNT)
      using iodine-131-labeled hypericin ([(131)I]-HYP) in combination with VDAs.

PMID- 21858710
TI  - Echocardiographic detection of coronary air embolism as the cause of cardiac
      arrest in a neonate with transposition of the great arteries.
AB  - A hemodynamically stable neonate with transposition of the great arteries
      suddenly went into cardiac arrest during preparation for transport to the
      operating room. Emergency echocardiography during cardiac massage detected
      coronary air embolism as the presumed cause of arrest. After about 15 minutes of
      resuscitation, it was possible to establish return of spontaneous circulation.
      Since the most likely source of air was the neonate's peripheral venous line, we
      have introduced inline microfilters for all neonates and all patients with right
      to-left shunt lesions and did not encounter proven air embolism thereafter.

PMID- 21858711
TI  - Comparing hydrogeomorphic approaches to lake classification.
AB  - A classification system is often used to reduce the number of different ecosystem
      types that governmental agencies are charged with monitoring and managing. We
      compare the ability of several different hydrogeomorphic (HGM)-based
      classifications to group lakes for water chemistry/clarity. We ask: (1) Which
      approach to lake classification is most successful at classifying lakes for
      similar water chemistry/clarity? (2) Which HGM features are most strongly related
      to the lake classes? and, (3) Can a single classification successfully classify
      lakes for all of the water chemistry/clarity variables examined? We use
      univariate and multivariate classification and regression tree (CART and MvCART)
      analysis of HGM features to classify alkalinity, water color, Secchi, total
      nitrogen, total phosphorus, and chlorophyll a from 151 minimally disturbed lakes
      in Michigan USA. We developed two MvCART models overall and two CART models for
      each water chemistry/clarity variable, in each case comparing: local HGM
      characteristics alone and local HGM characteristics combined with
      regionalizations and landscape position. The combined CART models had the highest
      strength of evidence (omega(i) range 0.92-1.00) and maximized within class
      homogeneity (ICC range 36-66%) for all water chemistry/clarity variables except
      water color and chlorophyll a. Because the most successful single classification
      was on average 20% less successful in classifying other water chemistry/clarity
      variables, we found that no single classification captures variability for all
      lake responses tested. Therefore, we suggest that the most successful
      classification (1) is specific to individual response variables, and (2)
      incorporates information from multiple spatial scales (regionalization and local
      HGM variables).

PMID- 21858712
TI  - Assessing integrated pest management adoption: measurement problems and policy
      implications.
AB  - For more than a decade, the U.S. government has promoted integrated pest
      management (IPM) to advance sustainable agriculture. However, the usefulness of
      this practice has been questioned because of lagging implementation. There are at
      least two plausible rationales for the slow implementation: (1) growers are not
      adopting IPM-for whatever reason-and (2) current assessment methods are
      inadequate at assessing IPM implementation. Our research addresses the second
      plausibility. We suggest that the traditional approach to measuring IPM
      implementation on its own fails to assess the distinct, biologically hierarchical
      components of IPM, and instead aggregates growers' management practices into an
      overall adoption score. Knowledge of these distinct components and the extent to
      which they are implemented can inform government officials as to how they should
      develop targeted assistance programs to encourage broader IPM use. We address
      these concerns by assessing the components of IPM adoption and comparing our
      method to the traditional approach alone. Our results indicate that there are
      four distinct components of adoption-weed, insect, general, and ecosystem
      management-and that growers implement the first two components significantly more
      often than the latter two. These findings suggest that using a more nuanced
      measure to assess IPM adoption that expands on the traditional approach, allows
      for a better understanding of the degree of IPM implementation.

PMID- 21858713
TI  - Skier and snowboarder motivations and knowledge related to voluntary
      environmental programs at an alpine ski area.
AB  - Many alpine ski areas have recently adopted voluntary environmental programs
      (VEPs) such as using recycling, renewable energy, and biofuels to help reduce
      their environmental impacts. Studies have addressed the performance of these VEPs
      in mitigating environmental impacts of this industry, but little is known about
      visitor awareness and perceptions of these programs. This article addresses this
      knowledge gap by exploring skier and snowboarder knowledge of VEPs at a ski area
      and the influence of these programs on their motivations to visit this area
      currently and behavioral intentions to visit again in the future. Data were
      obtained from an onsite survey at the Mt. Bachelor ski area in Oregon, USA (n =
      429, 89.7% response rate). Few skiers and snowboarders were knowledgeable of VEPs
      at this area and fewer than 20% were motivated to visit on their current trip
      because of these programs. Other attributes such as scenery, snow conditions, and
      access were more important for influencing visitation. Up to 38% of skiers and
      snowboarders, however, intend to visit this ski area more often if it adopts and
      promotes more VEPs. Managers can use these results to inform communication and
      marketing of their environmental programs and performance to visitors. Additional
      implications for management and future research are discussed.

PMID- 21858714
TI  - Influence of novel nano-mesoporous bioactive glass on the regulation of IGF-II
      gene expression in osteoblasts.
AB  - To investigate whether the mesoporous bioactive glass (MBG) exerts any in vitro
      bioactivity on rat osteoblasts and the potential regulatory mechanism of this
      bioactivity. Rat osteoblasts were incubated in the presence and absence (control)
      of ionic dissolution product of MBG in minimal essential medium. The osteoblast
      proliferation and differentiation were measured using MTT and alkaline
      phosphatase methods. The IGF-II mRNA expression in osteoblasts was measured by RT
      PCR. IGF-II protein and IGFBP were measured by ELISA. The level of alkaline
      phosphatase activity was increased to 125% of control. Expression of IGF-II mRNA
      was increased to 125% of control. There was a 175 and 237% increase in the
      concentration of unbound IGF-II protein and IGFBP, respectively, in the
      conditioned media of treated osteoblasts. The osteoblast proliferation was 92% of
      control. The ionic dissolution product of MBG was able to promote the
      differentiation of osteoblasts, probably by inducing IGF-II expression at both
      mRNA and protein level.

PMID- 21858715
TI  - Vocal fold immobility and aspiration status: a direct replication study.
AB  - The purpose of this direct replication study was to confirm the incidence of
      vocal fold immobility (VFI) and its relationship to pharyngeal dysphagia and
      aspiration. Using a single-group consecutively referred case series, a total of
      2,650 participants underwent fiberoptic endoscopic evaluation of swallowing
      between August 2003 and December 2007. Main outcome measures included overall
      incidence of VFI and aspiration status, with specific emphasis on age, gender,
      etiology and pharyngeal phase bolus flow characteristics, and side of VFI (right,
      left, or bilateral). These data were compared to and then combined with the
      original study (n = 1,452) for a total of 4,102 participants. Results indicated
      that the incidence of VFI was 4.3% (112/2,650), i.e., 27% (31/112) unilateral
      right, 58% (65/112) unilateral left, and 14% (16/112) bilateral. Incidence of
      aspiration was 22% (580/2,650). Of those with VFI, 40% (45/112) aspirated, i.e.,
      42% (13/31) unilateral right, 37% (24/65) unilateral left, and 50% (8/16)
      bilateral. An individual with VFI had 2.50 times the odds of aspirating as
      someone without VFI (95% CI = 1.86-3.37). For liquid aspiration, the odds ratio
      (OR) = 2.41 (95% CI = 1.77-3.28), and for puree aspiration, OR = 2.08 (95% CI =
      1.47-2.93). Left VFI occurred most frequently due to surgical trauma. Liquid was
      aspirated more often than a puree. Males exhibited VFI more often than females.
      Side of VFI and age were not factors that increased the incidence of aspiration
      significantly. It was confirmed that VFI is not an uncommon finding during
      dysphagia testing and, when present, increased the odds of aspiration compared to
      a population already being evaluated for dysphagia.

PMID- 21858717
TI  - International standards in cases of mass Disaster Victim Identification (DVI).

PMID- 21858716
TI  - DVI missions in the Carribean-the practical aspects of disaster victim
      identification.
AB  - Human trafficking of young men from Africa to Europe is a crime with often
      devastating consequences. The African continent loses members of the younger
      generation and many die during the attempt to reach their destinations. The
      identification of these victims is often difficult, however the structured and by
      now well-established procedures utilizing standard disaster victim identification
      protocols provide a reliable and functional approach. The logistics involved are
      straightforward, and one of the many functions of the team leader is to monitor
      and control the flow of cases through the system. The importance of ante mortem
      data for the purposes of identification is clear-no ante mortem data means no
      identification. Two different missions conducted in the Caribbean are described
      to illustrate particular difficulties that may occur.

PMID- 21858718
TI  - Informational and decisional empowerment in online health support communities:
      initial psychometric validation of the Cyber Info-Decisional Empowerment Scale
      (CIDES) and preliminary data from administration of the scale.
AB  - PURPOSE: This article presents initial psychometric validation of an instrument
      developed to measure cyber informational and decisional empowerment. The article
      provides preliminary insights into the extent to which cyber patients view the
      digital environment of peer-based information and support as a resource for
      informed and empowered participation in self health care management. METHODS:
      Data come from cancer patients (N = 350) who participated in the Study of Virtual
      Health Networks for Cancer Patients of the 21st Century. Data were first analyzed
      using exploratory factor analysis with principle component extraction and Varimax
      rotation. Age-based split-sample analysis (>= 51 and <= 50) was performed on a
      subsample, which consisted of only women (N = 255), in order to cross-validate
      psychometric data obtained from the full sample. A confirmatory factor analysis
      was conducted using AMOS 19.0. to further validate the scale. RESULTS: The
      composite scale is unidimensional with excellent internal consistency
      reliability. The highest average scores were obtained for informational
      empowerment items. The lowest average was for the item that measured empowerment
      to seek second opinion from additional health care professionals. CONCLUSIONS:
      The ability of this composite measure to provide information about the extent to
      which computer-connected patients view digital peer support as an empowerment
      tool makes it a valuable addition to the literature in health informatics,
      supportive cancer care, and health quality of life research.

PMID- 21858719
TI  - A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in
      the lens opacity 13 (lop13) mouse.
AB  - Lens opacity 13 (lop13) is a spontaneous, autosomal recessive mouse mutant that
      exhibits nuclear cataracts. Histological analysis revealed swollen lens fiber
      cells and the presence of bladder cells within the lens cortex, as well as
      morgagnian globules and liquefied material at the lens posterior. At 3 months of
      age, in addition to cataracts, lop13 mice also develop persistent skin wounds.
      Linkage analysis assigned the lop13 locus to a 1.1-Mb region on mouse Chr 15,
      encompassing 19 candidate genes. Sequence analysis identified a C3112T mutation
      in exon 18 of Sterol Regulatory Element Binding-Transcription Factor 2 (Srebf2)
      resulting in the R1038C substitution of a highly conserved arginine within the
      Srebf2 regulatory domain. Srebf2 belongs to a family of membrane-bound basic
      helix-loop-helix leucine zipper transcription factors that control the expression
      of genes involved in the biosynthesis and uptake of cholesterol and fatty acids.
      The lack of complementation observed in Srebf2 ( lop13/GT ) compound
      heterozygotes carrying the Srebf2 gene trapped allele (Srebf2 ( GT )) provides
      genetic evidence that the identified C3112T substitution in Srebf2 is responsible
      for the lop13 phenotype. Gas chromatography analysis identified lower levels of
      cholesterol in the lop13 brain, liver, and lens when compared to wild-type mice.
      These findings suggest that lop13 is a hypomorphic mutation in Srebf2. As such,
      the lop13 mouse presents an invaluable in vivo model for studying the
      contribution of Srebf2 and cholesterol to maintaining the homeostasis of the lens
      and skin.

PMID- 21858720
TI  - Genetic dissection of testis weight in mice: quantitative trait locus analysis
      using F(2) intercrosses between strains with extreme testis weight, and
      association study using Y-consomic strains.
AB  - In the present study, dissection of genetic bases of testis weight in mice was
      performed. Autosomes and the X chromosome were searched using traditional
      quantitative trait locus (QTL) scans, and the Y chromosome was searched by
      association studies of Y-consomic strains. QTL analysis was performed in ?DDD *
      ?CBA F(2) mice; the inbred mouse DDD has the heaviest testes, whereas the inbred
      mouse CBA has the lightest testes. Two significant testis weight QTLs were
      identified on chromosomes 1 and X. A DDD allele was associated with increased and
      decreased testis weight at the locus on chromosomes 1 and X, respectively. In the
      reciprocal cross ?CBA * ?DDD F(2) mice, QTL on chromosome 1, and not on
      chromosome X, had a significant effect on testis weight. The DDD allele at the X
      linked locus could not sustain testis weight in combination with the Y chromosome
      of the CBA strain. The Y chromosome per se had a significant effect on testis
      weight, i.e., DH-Chr Y(DDD) had significantly heavier testes than DH-Chr Y(CBA).
      On the basis of the results of Y-chromosome-wide association studies using 17 Y
      consomic strains, variations in Uty, Usp9y, and Sry were significantly associated
      with testis weight. Thus, testis weight is a complex quantitative phenotype
      controlled by multiple genes on autosomes and sex chromosomes and their
      interactions.

PMID- 21858721
TI  - Crystallinity assessment and in vitro cytotoxicity of polylactide scaffolds for
      biomedical applications.
AB  - Bioresorbable polylactides are one of the most important materials for tissue
      engineering applications. In this work we have prepared scaffolds based on the
      two optically pure stereoisomers: poly(L: -lactide) (PLLA) and poly(D: -lactide)
      (PDLA). The crystalline structure and morphology were evaluated by DSC, AFM and X
      ray diffraction. PLLA and PDLA crystallized in the alpha form and the equimolar
      PLLA/PDLA blend, crystallized in the stereocomplex form, were analyzed by a
      proliferation assay in contact with mouse L-929 and human fibroblasts and
      neonatal keratinocytes for in vitro cytotoxicity evaluation. SEM analysis was
      conducted to determine the cell morphology, spreading and adhesion when in
      contact with the different polymer surfaces. The preserved proliferation rate
      showed in MTT tests and the high colonization on the surface of polylactides
      observed by SEM denote that PLLA, PDLA and the equimolar PLLA/PDLA are useful
      biodegradable materials in which the crystalline characteristics can be tuned for
      specific biomedical applications.

PMID- 21858722
TI  - The effect of bone ingrowth depth on the tensile and shear strength of the
      implant-bone e-beam produced interface.
AB  - New technologies, such as selective electron beam melting, allow to create
      complex interface structures to enhance bone ingrowth in cementless implants. The
      efficacy of such structures can be tested in animal experiments. Although animal
      studies provide insight into the biological response of new structures, it
      remains unclear how ingrowth depth is related to interface strength.
      Theoretically, there could be a threshold of ingrowth, above which the interface
      strength does not further increase. To test the relationship between depth and
      strength we performed a finite element study on micro models with simulated
      uncoated and hydroxyapatite (HA) coated surfaces. We examined whether complete
      ingrowth is necessary to obtain a maximal interface strength. An increase in bone
      ingrowth depth did not always enhance the bone-implant interface strength. For
      the uncoated specimens a plateau was reached at 1,500 MUm of ingrowth depth. For
      the specimens with a simulated HA coating, a bone ingrowth depth of 500 MUm
      already yielded a substantial interface strength, and deeper ingrowth did not
      enhance the interface strength considerably. These findings may assist in
      optimizing interface morphology (its depth) and in judging the effect of bone
      ingrowth depth on interface strength.

PMID- 21858723
TI  - Electrophoretic deposition of porous CaO-MgO-SiO2 glass-ceramic coatings with
      B2O3 as additive on Ti-6Al-4V alloy.
AB  - The sub-micron glass-ceramic powders in CaO-MgO-SiO(2) system with 10 wt%
      B(2)O(3) additive were synthesized by sol-gel process. Then bioactive porous CaO
      MgO-SiO(2) glass-ceramic coatings on Ti-6Al-4V alloy substrates were fabricated
      using electrophoretic deposition (EPD) technique. After being calcined at 850
      degrees C, the above coatings with thickness of 10-150 MUm were uniform and crack
      free, possessing porous structure with sub-micron and micron size connected
      pores. Ethanol was employed as the most suitable solvent to prepare the
      suspension for EPD. The coating porous appearance and porosity distribution could
      be controlled by adjusting the suspension concentration, applied voltage and
      deposition time. The heat-treated coatings possessed high crystalline and was
      mainly composed of diopside, akermanite, merwinite, calcium silicate and calcium
      borate silicate. Bonelike apatite was formed on the coatings after 7 days of
      soaking in simulated body fluid (SBF). The bonding strength of the coatings was
      needed to be further improved.

PMID- 21858724
TI  - Modelling of the outcome of non-inferiority trials by integration of historical
      data.
AB  - The approval and differentiation of new compounds in clinical development often
      demands non-inferiority trials, in which the test drug is compared against a
      reference treatment. However, non-inferiority trials impose major operational
      burden with serious ethical and scientific implications for the development of
      new medicines. Traditional approaches make limited use of historical information
      on placebo and neglect inter-trial variability, relying on the constancy
      assumption that the control-to-placebo effect size is maintained across trials.
      We propose a model-based approach that overcomes such limitations and may be used
      as a tool to explore differentiation during clinical development. Parameter
      distributions are introduced which reflect the heterogeneity of trials. The
      method is illustrated using data from impetigo trials. Based on simulation
      scenarios, this Bayesian technique yields a definitive, consistent increase in
      the statistical power over two accepted statistical methods, allowing lower
      sample size requirements for the assessment of non-inferiority.

PMID- 21858725
TI  - Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen
      and hemin in adjuvant-induced arthritis in the Wistar rat.
AB  - AIM: Although, pharmacological activation of heme oxygenase (HO)-1 has shown to
      produce ameliorative effects in various experimental models of inflammation, but
      such beneficial effects have not been observed in adjuvant-induced arthritis.
      Further, the upregulated activity of HO-1 has been implicated in the pathogenesis
      of adjuvant arthritis. The present study was designed to investigate the anti
      inflammatory and antihyperalgesic effects of the prophylactic use of hemin alone
      and/or in combination with ibuprofen using adjuvant-induced arthritis in Wistar
      rat. METHODS: Arthritis was induced by an intradermal injection of complete
      Freund's adjuvant (CFA) into left hind paw. Paw volume, thermal hyperalgesia,
      mechanical allodynia, joint stiffness and mobility behaviors (score) were
      measured. RESULTS: Administration of ibuprofen (8.75, 17.5, 35 mg/kg/day, p.o.)
      and hemin (1, 5, 10 mg/kg/day, i.p.) were significantly effective in suppressing
      CFA-induced paw oedema, thermal and mechanical hyperalgesia, joint stiffness and
      mobility. The combination of low doses of ibuprofen (8.75 mg/kg, p.o.) and hemin
      (1 mg/kg, i.p.) significantly reduced paw volume, thermal and mechanical
      hyperalgesia, as compared to the individual dose of the ibuprofen and hemin
      alone. CONCLUSIONS: Hence, it may be concluded that the prophylactic
      administration of either hemin produced significantly enhanced anti-inflammatory
      and analgesic effects. Further, concurrent low dose administration of hemin and
      ibuprofen produced significantly enhanced anti-inflammatory and analgesic
      effects, as compared to the either treatment alone, in CFA-induced arthritis in
      Wistar rats.

PMID- 21858726
TI  - Spinal growth modulation using a novel intravertebral epiphyseal device in an
      immature porcine model.
AB  - PURPOSE: Fusionless growth modulation is an attractive alternative to
      conventional treatments of idiopathic scoliosis. To date, fusionless devices
      achieve unilateral growth modulation by compressing the intervertebral disc. This
      study explores a device to control spinal alignment and vertebral morphology via
      growth modulation while excluding the disc in a porcine model. METHODS: A device
      that locally encloses the vertebral growth plate exclusive of the disc was
      introduced anteriorly over T5-T8 in four immature pigs (experimental) while three
      underwent surgery without instrumentation (sham) and two were selected as
      controls. Bi-weekly coronal and lateral radiographs were taken over the 12-week
      follow-up to document vertebral morphology and spinal alignment modifications via
      an inverse approach (creation of deformity). RESULTS: All animals completed the
      experiment with no postoperative complications. Control and sham groups showed no
      significant changes in spinal alignment. Experimental group achieved a final
      coronal Cobb angle of 6.5 degrees  +/- 3.5 degrees  (constrained to the four
      instrumented levels) and no alteration to the sagittal profile was observed.
      Solely the experimental group ended with consistent vertebral wedging of 4.1
      degrees  +/- 3.6 degrees  amounting to a cumulative wedging of up to 25 degrees 
      and a concurring difference in left/right vertebral height of 1.24 +/- 1.86 mm in
      the coronal plane. CONCLUSIONS: The proposed intravertebral epiphyseal device,
      for the early treatment of progressive idiopathic scoliosis, demonstrated its
      feasibility by manipulating spinal alignment through the realization of local
      growth modulation exclusive of the intervertebral disc.

PMID- 21858727
TI  - Parental attitudes toward medicine use in children in Finland.
AB  - OBJECTIVE: The aim was to describe parental attitudes towards medicine use in
      children, and the factors associated with them. SETTING: A cross-sectional
      population survey of a random sample of children under 12 years of age (n =
      6,000) was carried out in Finland in the spring of 2007, with a response rate of
      67%. METHOD: A questionnaire was sent to their parents. A Principal Component
      Analysis was conducted for the attitudinal scale to determine parental attitudes.
      MAIN OUTCOME MEASURE: An attitudinal scale including 21 items on five-point
      Likert scale was used to determine parental attitudes towards medicines. RESULTS:
      Five principal components with 18 statements explained parental attitudes:
      General attitude towards medicines, Attitude towards prescription medicines,
      Attitude towards OTC medicines, Attitude towards the risks of medicines, and
      Attitude towards long-term use of pain-killers. These components were internally
      consistent and explained 54.7% of the total variance. Of the respondents, 15%
      were cautious towards medicine use, 84% agreed that prescription medicines are
      safe and effective, whereas 49% thought so about OTC medicines. Of the
      respondents, 69% were worried about the risks of medicines, especially parents
      older than 46 years, with a low level of education, who used medicinal herbs
      themselves, and had a child with a long-term illness. Moreover, 46% of the
      respondents were worried about the long-term use of pain-killers. CONCLUSION:
      This population based study showed that the parental attitudes toward
      prescription medicines and toward OTC medicines are different: many parents
      consider prescription medicines as safe and effective, less think so of OTC
      medicines. A considerable proportion of parents had worries about side effects
      and interactions. This stresses the need to address these topics in encounters
      with parents.

PMID- 21858728
TI  - Relationships of ESR1 and XBP1 expression in human breast carcinoma and stromal
      cells isolated by laser capture microdissection compared to intact breast cancer
      tissue.
AB  - Results from investigations of human genomics which utilize intact tissue biopsy
      specimens maybe compromised due to a host of uncontrolled variables including
      cellular heterogeneity of a sample collected under diverse conditions, then
      processed and stored using different protocols. To determine the cellular origin
      and assess relationships of mRNA expression of two genes reported to be co
      expressed in human breast carcinoma (estrogen receptor-alpha, ESR1 and X-box
      binding protein 1, XBP1), gene expression analyses were performed with intact
      tissue sections and compared with those of laser capture microdissection (LCM)
      procured carcinoma and stromal cells from serial sections of the same tissue.
      Frozen sections of human breast carcinomas were first evaluated for structural
      integrity and pathology after hematoxylin and eosin (H&E) staining. Total RNA
      preparations from intact tissue sections and LCM-procured carcinoma and stromal
      cells were reverse transcribed for measurements of ESR1 and XBP1 expression by
      quantitative PCR (qPCR). These results were compared with those obtained from
      microarray analyses of LCM-procured carcinoma cells. Levels of ESR1 and XBP1 were
      detected in the intact breast cancer tissue sections suggesting coordinate gene
      expression. Although coordinate expression of these genes was observed in the LCM
      procured carcinoma cells, it was not discerned in LCM-procured stromal cells. The
      origin of coordinate expression of ESR1 and XBP1 observed in whole tissue
      sections of human breast cancer biopsies is due principally to their co
      expression in carcinoma cells and not in the surrounding stromal cells as
      substantiated using LCM-procured cells. Collectively, a microgenomic process was
      established from human tissue preparation to RNA characterization and analysis to
      identify molecular signatures of specific cell types predicting clinical
      behavior.

PMID- 21858729
TI  - Matrix metalloproteinase-1 expression enhances tumorigenicity as well as tumor
      related angiogenesis and is inversely associated with TIMP-4 expression in a
      model of glioblastoma.
AB  - Herein we continue the study of matrix metalloproteinase-1 (MMP-1) with respect
      to glioblastoma multiforme (GBM) cell tumorigenicity and angiogenesis. A model of
      tumorigenicity with cells stably altered to over-express or knock-down MMP-1
      revealed that it significantly increases tumor incidence and size. Organized
      endothelial growth in human umbilical vein endothelial cell (HUVEC)-GBM co
      cultures was significantly increased in the presence of MMP-1. CD31 analysis of
      model tumors elucidated a substantial recruitment of endothelium in MMP-1
      enhanced samples. Antibody arrays indicated an inverse expression of certain anti
      angiogenic factors with respect to MMP-1, the most notable of which was a
      significant increase in tissue inhibitor of metalloproteinases-4 (TIMP-4) in the
      absence of MMP-1, as validated by immunoblot.

PMID- 21858730
TI  - Viral nucleoprotein localization and lesions of Newcastle disease in tissues of
      indigenous ducks.
AB  - Localization of Newcastle disease viral nucleoprotein and pathological lesions
      was evaluated in tissues of 55 indigenous ducks (45 experimentally infected and
      10 sentinel ones). In addition, ten Newcastle disease infected chickens were used
      to ensure that the virus inoculum administered to the ducks produced the disease
      in chickens, the susceptible hosts. Ducks were killed on day 1, 4, 8 and 14 post
      infection. Post-mortem examination was done with six tissues (liver, spleen,
      lung, caecal tonsils, kidneys and brain) being collected from each bird. The
      tissues were preserved in 10% neutral formalin for 24 h. They were then
      transferred to 70% ethanol for histology and immunohistochemical staining.
      Airsacculitis, necrotic splenic foci, congested intestines, lymphoid depleted
      caecal tonsils and focal infiltrations by mononuclear cells were the main
      pathological lesions in infected ducks. Over 28.9% of the infected ducks had
      Newcastle disease viral nucleoprotein in macrophage-like large mononuclear cells
      in the caecal tonsils and kidney tubular epithelium. The viral antigens were
      located in the cytoplasm and nucleolus of the cells. The other organs had no
      detectable viral antigens. This study shows that the kidneys and caecal tonsils
      are the likely predilection sites for the virus in ducks. They thus need to be
      considered as diagnostic indicators for the viral carriage in ducks.

PMID- 21858731
TI  - Improved obesity reduction and co-morbidity resolution in patients treated with
      40-French bougie versus 50-French bougie four years after laparoscopic sleeve
      gastrectomy. Analysis of 294 patients.
AB  - BACKGROUND: We compared percent excess body mass index loss (%EBMIL) and
      resolution of dyslipidaemia, hypertension, and type 2 diabetes mellitus in the 4
      years following laparoscopic sleeve gastrectomy (LSG) between patients calibrated
      with a 40-French (40F) or a 50-French (50F) bougie. METHODS: We conducted a
      longitudinal retrospective descriptive study of routinely collected pre- and post
      surgical data from 294 patients who underwent LSG at a single surgical centre
      (50F--n = 106, 40F--n = 185). Obesity measurements were taken prior to surgery
      and at regular intervals until 48 months post-surgery. Co-morbidity resolution
      was also assessed across the 48-month observation period. Multivariate regression
      modelling was used to control analyses for baseline obesity and sociodemographic
      variables. RESULTS: At 48 months post-surgery mean (+/-SD) %EBMIL was 60.2 +/-
      27.6% and 45.4 +/- 38.4% for those treated with the 40F and 50F bougie,
      respectively. After controlling for sociodemographic variables and baseline
      excess weight, mean %EBMIL was 15.5% greater with a 40F bougie compared with a
      50F bougie at the end of follow-up. The likelihood of dyslipidaemia resolution
      within 48 months post-LSG was 19.0 times greater (p = 0.006), hypertension
      resolution 3.6 times greater (p = 0.005) and type 2 diabetes mellitus resolution
      5.2 times greater (p = 0.034) by 4 years post-surgery in patients treated with
      the 40F bougie compared with a 50F bougie. CONCLUSION: Improved obesity reduction
      and resolution of dyslipidaemia, hypertension and type 2 diabetes mellitus is
      experienced during the 4 years following surgery by patients treated with a 40F
      bougie compared with the 50F. These findings remain when controlling for
      potential confounding clinical and sociodemographic factors.

PMID- 21858733
TI  - Twice random, once mixed: applying mixed models to simultaneously analyze random
      effects of language and participants.
AB  - Psychologists, psycholinguists, and other researchers using language stimuli have
      been struggling for more than 30 years with the problem of how to analyze
      experimental data that contain two crossed random effects (items and
      participants). The classical analysis of variance does not apply; alternatives
      have been proposed but have failed to catch on, and a statistically
      unsatisfactory procedure of using two approximations (known as F(1) and F(2)) has
      become the standard. A simple and elegant solution using mixed model analysis has
      been available for 15 years, and recent improvements in statistical software have
      made mixed models analysis widely available. The aim of this article is to
      increase the use of mixed models by giving a concise practical introduction and
      by giving clear directions for undertaking the analysis in the most popular
      statistical packages. The article also introduces the DJMIXED: add-on package for
      SPSS, which makes entering the models and reporting their results as
      straightforward as possible.

PMID- 21858732
TI  - Ambulatory blood pressure status in children: comparing alternate limit sources.
AB  - The American Heart Association has included alternate ambulatory blood pressure
      (ABP) limits for children published by Wuhl in 2002. These updated limits employ
      the same pediatric cohort data as the previous ABP limits published by Soergel in
      1997 but differ in analysis technique. The implications of changing ABP limit
      source on the diagnosis of hypertension has yet to be examined in a large
      pediatric cohort. We reviewed 741 ABP monitorings performed in children referred
      to our hypertension clinic between 1991-2007. Hypertension was defined as 24-h
      mean blood pressure >= 95 th percentile or 24-h blood pressure load >= 25%, by
      Soergel and Wuhl limits separately. Six hundred seventy-three (91%) children were
      classified the same by both limit sources. Wuhl limits were more likely than
      Soergel to classify a child as hypertensive (443 vs. 409, respectively). There
      was an increased classification of prehypertension and decreased white-coat
      hypertension by the Wuhl method, whereas ambulatory and severe hypertension
      counts remained relatively the same by both limits sources. The use of either
      limit source will not significantly affect most clinical outcomes but should
      remain consistent over long-term research projects. Collection of new normative
      data from a larger, multiethnic population is needed for better measurement of
      ABP in children.

PMID- 21858734
TI  - Alleviation of cisplatin-induced acute kidney injury using phytochemical
      polyphenols is accompanied by reduced accumulation of indoxyl sulfate in rats.
AB  - BACKGROUND: Polyphenols such as quercetin have been reported to prevent cisplatin
      induced acute kidney injury (AKI). Indoxyl sulfate (IS), a uremic toxin generated
      in the liver, is increased in cisplatin AKI. The present study examined the
      effect of phytochemical polyphenols on serum and renal accumulations of IS in
      association with cisplatin AKI. METHODS: Sprague-Dawley rats were treated with
      cisplatin (10 mg/kg body weight) by intraperitoneal injection. Polyphenols were
      orally administered at -24, -1, 24 and 48 h before or after cisplatin injection.
      Serum levels of IS, cisplatin, serum creatinine (SCr), blood urea nitrogen (BUN)
      and electrolytes were measured. By using an in vitro assay system with rat liver
      S9 fraction, the inhibitory potencies of several compounds on IS production were
      determined. RESULTS: Injection of cisplatin in rats markedly elevated the SCr and
      BUN levels, which were accompanied by tubular injuries and the expression of
      kidney injury molecule-1 (Kim-1). By contrast, quercetin significantly suppressed
      the SCr and BUN levels in the cisplatin-treated rats and protected them against
      renal injury with the decreased expression of Kim-1. Quercetin had no effect on
      serum and renal levels of cisplatin. In addition, quercetin had no effect on
      cisplatin-induced renal accumulation of malondialdehyde. IS concentrations in
      serum, kidney, liver, intestine and lung were markedly elevated by cisplatin
      treatment, whereas quercetin suppressed the serum and tissue IS levels. An in
      vitro kinetic assay revealed that quercetin displayed a potent inhibitory effect
      on hepatic production of IS. CONCLUSION: Inhibition of IS accumulation by oral
      administration of quercetin alleviates cisplatin-induced AKI.

PMID- 21858736
TI  - Assessment of landfill leachate toxicity reduction after biological treatment.
AB  - In the present article, the efficiency of biological treatment of landfill
      leachates was evaluated by implementation of physicochemical characterisation and
      a complex toxicity assessment. An array of toxicity tests using bacterium Vibrio
      fischeri, alga Desmodesmus subspicatus, crustacean Daphnia magna, and embryo of
      fish Danio rerio, as well as unconventional methods using biochemical biomarkers
      (protein content, enzymes cholinesterase, and glutathione-S-transferase), were
      employed. Toxicity of leachates varied depending on the season of collection in
      relation to their different physicochemical characteristics. Uncommon effects of
      leachates on organisms, such as hormetic-like increases of algal growth and
      reproduction of daphnids, were identified. New approaches using the activities of
      enzymes were found unsuitable for routine hazard assessment of leachates.
      Although physicochemical parameters and toxicity decreased significantly after
      biological treatment, the effluents did not meet the demands of the current
      Slovenian legislation; thus, the existing biological treatment was found
      inappropriate. The development of advanced treatment techniques for landfill
      leachates is thus encouraged.

PMID- 21858735
TI  - Effects of nicorandil on the reduction of BNP levels in patients with chronic
      kidney disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) still frequently
      experience cardiovascular events despite recent progress in treatment. We
      examined whether nicorandil, a hybrid nitrate and adenosine triphosphate
      sensitive potassium channel opener, could improve a biomarker and physiological
      markers of cardiovascular events. METHODS: Patients with advanced stage CKD
      (stage III-V with or without peritoneal dialysis) were included in this trial if
      they were considered at high risk for cardiovascular events [past history of
      cardiovascular diseases, past history of coronary angiography, presence of
      endothelial dysfunction measured by reactive hyperemia peripheral arterial
      tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients
      were randomly assigned to be treated with or without oral nicorandil, 15 mg/day.
      BNP values and endothelial function (augmentation index, pulse wave velocity, and
      reactive hyperemia peripheral arterial tonometry) before and 1 month after the
      initiation of the trial were assessed. RESULTS: Nineteen patients (15 men, 4
      women) with a mean age of 61 +/- 10 (SD) years were included. The median baseline
      BNP value was 75.3 (interquartile range, 32.1-138.8) pg/ml, and the BNP level was
      significantly reduced in the nicorandil group (P < 0.05). Regression analysis
      demonstrated that only the use of nicorandil is related to a decrease of BNP
      levels [standardized beta coefficient, -75.1 (95% CI, -19.7 to -130.6), P =
      0.01]. There were no significant changes in the rest of the parameters in the
      nicorandil group in comparison to the control group. The change in BNP levels was
      correlated with changes in the augmentation index (P < 0.01) and central pulse
      pressure (P = 0.03). CONCLUSIONS: Nicorandil treatment may reduce the level of
      BNP by reducing the central blood pressure in CKD patients.

PMID- 21858737
TI  - Mercury and nitrogen isotope in a marine species from a tropical coastal food
      web.
AB  - The present study raised the hypothesis that the trophic status in a tropical
      coastal food web from southeastern Brazil can be measured by the relation between
      total mercury (THg) and nitrogen isotope (delta(15)N) in their components. The
      analysed species were grouped into six trophic positions: primary producer
      (phytoplankton), primary consumer (zooplankton), consumer 1 (omnivore shrimp),
      consumer 2 (pelagic carnivores represented by squid and fish species), consumer 3
      (demersal carnivores represented by fish species) and consumer 4 (pelagic
      demersal top carnivore represented by the fish Trichiurus lepturus). The values
      of THg, delta(15)N, and trophic level (TLv) increased significantly from primary
      producer toward top carnivore. Our data regarding trophic magnification (6.84)
      and biomagnification powers (0.25 for delta(15)N and 0.83 for TLv) indicated that
      Hg biomagnification throughout trophic positions is high in this tropical food
      web, which could be primarily related to the quality of the local water.

PMID- 21858739
TI  - Work disability prevention research: current and future prospects.
AB  - Work disability prevention has evolved from being a component of disease outcomes
      studies, to a separate and growing research discipline. In part, this is due to
      recognition that work outcomes often do not correlate with other health outcomes;
      the causes of work disability are multiple, complex, and often distinct from
      associated health conditions or treatments; and that work disability creates an
      important personal, economic and social burden that is often preventable.
      Conceptual frameworks, measures, research methods and interventions specific to
      this area have been developed, many have been validated across different
      contexts, and an international community of researchers and trainees in work
      disability prevention has formed. The articles included in this special section
      exemplify the breadth of current research in this field, and future opportunities
      for greater cross- disciplinary collaboration and translation of research to
      practical implementation and policy interventions.

PMID- 21858740
TI  - Micelle-enhanced spectrofluorimetric method for determination of cholesterol
      reducing drug ezetimibe in dosage forms.
AB  - A simple and sensitive spectrofluorimetric method was developed for the
      determination of ezetimibe in its pharmaceutical formulations. The proposed
      method is based on investigation of the fluorescence spectral behavior of
      ezetimibe in sodium dodecyl sulfate (SDS) micellar system. In aqueous solution of
      acetate buffer pH 5.0, the fluorescence intensity of ezetimibe was greatly
      enhanced, 200% enhancement, in the presence of SDS. The fluorescence intensity of
      ezetimibe was measured at 380 nm after excitation at 268 nm. The fluorescence
      concentration plot was rectilinear over the range of 0.03-3.0 MUg/mL with lower
      detection limit of 3.08 * 10(-3) MUg/mL. The method was successfully applied to
      the analysis of ezetimibe in its commercial tablets; the results were in good
      agreement with those obtained with the reported method. The application of the
      proposed method was extended to the stability studies of ezetimibe after exposure
      to different forced degradation conditions, such as acidic, alkaline, photo and
      oxidative conditions, according to ICH guidelines.

PMID- 21858738
TI  - Thrombin and vascular inflammation.
AB  - Vascular endothelium is a key regulator of homeostasis. In physiological
      conditions it mediates vascular dilatation, prevents platelet adhesion, and
      inhibits thrombin generation. However, endothelial dysfunction caused by physical
      injury of the vascular wall, for example during balloon angioplasty, acute or
      chronic inflammation, such as in atherothrombosis, creates a proinflammatory
      environment which supports leukocyte transmigration toward inflammatory sites. At
      the same time, the dysfunction promotes thrombin generation, fibrin deposition,
      and coagulation. The serine protease thrombin plays a pivotal role in the
      coagulation cascade. However, thrombin is not only the key effector of
      coagulation cascade; it also plays a significant role in inflammatory diseases.
      It shows an array of effects on endothelial cells, vascular smooth muscle cells,
      monocytes, and platelets, all of which participate in the vascular
      pathophysiology such as atherothrombosis. Therefore, thrombin can be considered
      as an important modulatory molecule of vascular homeostasis. This review
      summarizes the existing evidence on the role of thrombin in vascular
      inflammation.

PMID- 21858741
TI  - Effects of serum protein on ionic exchange between culture medium and microporous
      hydroxyapatite and silicate-substituted hydroxyapatite.
AB  - It has been proposed that one of the underlying mechanisms contributing to the
      bioactivity of osteoinductive or osteoconductive calcium phosphates involves the
      rapid dissolution and net release of calcium and phosphate ions from the matrix
      as alternatively a precursor to subsequent re-precipitation of a bone-like
      apatite at the surface and/or to facilitate ion exchange in biochemical
      processes. In order to confirm and evaluate ion release from sintered
      hydroxyapatite (HA) and to examine the effect of silicate substitution into the
      HA lattice on ion exchange under physiological conditions we monitored Ca(2+),
      PO(4)(3-) and SiO(4)(4-) levels in Earl's minimum essential medium (E-MEM) in the
      absence (serum-free medium, SFM) or presence (complete medium, C-MEM) of foetal
      calf serum (FCM), with both microporous HA or 2.6 wt% silicate-substituted HA
      (SA) sintered discs under both static and semi-dynamic (SD) conditions for up to
      28 days. In SFM, variation in Ca(2+) ion concentration was not observed with
      either disc chemistry or culture conditions. In C-MEM, Ca(2+) ions were released
      from SA under static and SD conditions whereas with HA Ca(2+) was depleted under
      SD conditions. PO(4)(3-) depletion occurred in all cases, although it was greater
      in C-MEM, particularly under SD conditions. SiO(4)(4-) release occurred from SA
      irrespective of medium or culture conditions but a sustained release only
      occurred in C-MEM under SD conditions. In conclusion we showed that under
      physiological conditions the reservoir of exchangeable ions in both HA and SA in
      the absence of serum proteins is limited, but that the presence of serum proteins
      facilitated greater ionic exchange, particularly with SA. These observations
      support the hypothesis that silicate substitution into the HA lattice facilitates
      a number of ionic interactions between the material and the surrounding
      physiological environment, including but not limited to silicate ion release,
      which may play a key role in determining the overall bioactivity and
      osteoconductivity of the material. However, significant net release of Ca(2+) and
      PO(4)(3-) was not observed, thus rapid or significant net dissolution of the
      material is not necessarily a prerequisite for bioactivity in these materials.

PMID- 21858742
TI  - Respiratory viral infections. Preface.

PMID- 21858743
TI  - Influenza: epidemiology, clinical features, therapy, and prevention.
AB  - Influenza A and B are important causes of respiratory illness in all age groups.
      Influenza causes seasonal outbreaks globally and, less commonly, pandemics. In
      the United States, seasonal influenza epidemics account for >200,000
      hospitalizations and >30,000 deaths annually. More than 90% of deaths occur in
      the elderly population. Interestingly, in the novel 2009 H1N1 influenza pandemic,
      attack rates were highest among children and young adults. Fewer than 10% of
      cases occurred in adults >60 years old, likely because preexisting antibodies
      against other H1N1 viruses afforded protection. Despite concerns about a high
      lethality rate with the novel 2009 H1N1 strain, most illnesses caused by the 2009
      H1N1 viruses were mild (overall case fatality rate <0.5%). Clinical features of
      influenza infection overlap with other respiratory pathogens (particularly
      viruses). The diagnosis is often delayed due to low suspicion and the limited use
      of specific diagnostic tests. Rapid diagnostic tests are widely available and
      allow detection of influenza antigen in respiratory secretions within 1 hour;
      however, sensitivity ranges from 50 to 90%. Neuraminidase inhibitors (NAIs) (eg,
      oseltamivir and zanamivir) are effective for treating influenza A or B and for
      prophylaxis in selected adults and children. Resistance to NAIs is rare, but
      influenza strains resistant to oseltamivir have been detected. Vaccines are the
      cornerstone of influenza control. Currently, trivalent inactivated vaccine (TIV)
      and live attenuated influenza vaccine (LAIV) are available. These agents reduce
      mortality and morbidity in high-risk patients (i.e., the elderly or patients with
      comorbidities), and expanding the use of vaccines to healthy children and adults
      reduces the incidence of influenza, pneumonia, and hospitalizations due to
      respiratory illnesses in the community.

PMID- 21858744
TI  - Pandemic novel 2009 H1N1 influenza: what have we learned?
AB  - In March 2009, cases of influenza-like illness in Mexico caused by a novel H1N1
      virus containing genes from swine, avian, and human influenza strains were
      reported. Within several weeks, 2009 H1N1 disseminated rapidly and was the
      predominant influenza strain globally. On June 11, 2009, the World Health
      Organization declared that criteria for an influenza pandemic had been met.
      Concern that this pandemic would rival the 1918 pandemic was high. Fortunately,
      that was not the case. Influenza-related disease activity peaked in late October
      to November 2009. By August 2010, the H1N1 influenza virus had moved into the
      postpandemic period. During the 2010-2011 season, influenza A H3N2 has been the
      predominant serotype, but the 2009 H1N1 continues to co-circulate with H3N2 and B
      strains. In contrast to previous seasonal influenza strains, the novel 2009 H1N1
      strain preferentially affected young adults, with a clustering of severe and
      fatal cases in adults between the ages of 30 and 50 years. Additionally, H1N1
      displayed a heightened potential for severe lung injury as well as
      gastrointestinal symptoms. Risk factors for severe disease included obesity,
      morbid obesity, pregnancy, immunosuppression, asthma (in children), chronic
      obstructive pulmonary disease, neurological disorders, other comorbidities, HIV
      infection, poverty, and lack of access to care. However, >25% of deaths were in
      previously healthy individuals. Molecular tools for identifying 2009 H1N1 were
      rapidly developed, but the volume of samples quickly overwhelmed available
      laboratory services. Further, in the early phases of the pandemic, the volume of
      patients presenting to emergency rooms, acute care clinics, and physician's
      offices overwhelmed health care resources. Fortunately, most cases were mild; in
      the United States, only one in 400 required intensive care unit care, and one in
      2000 died. Because most infected individuals have mild, self-limited disease, the
      risk/benefit assessment for early access to antiviral agents must balance the
      potential benefit for reducing transmission, disease severity, and burden on
      health care providers against the potential for dissemination of viral resistance
      and drug-related adverse events. Monovalent vaccines against 2009 H1N1 were
      developed and ready for distribution by September 2009, but initial supplies were
      inadequate to impact the bulk of cases that occurred in the Northern Hemisphere
      between April and September 2009. Continued efforts to develop universal vaccines
      and improve access to effective vaccines are critical.

PMID- 21858745
TI  - H1N1 influenza: critical care aspects.
AB  - During the Northern Hemisphere spring of 2009, a novel H1N1 influenza A virus
      emerged in Mexico, causing widespread human infection and acute critical
      respiratory illness. The 2009 H1N1 virus spread initially to the United States
      and Canada, with subsequent rapid global dissemination, leading the World Health
      Organization (WHO) to declare "a public health emergency of international
      concern" in April 2009, and upgrading the viral threat to pandemic status in June
      2009. Despite initial fears, the severity of the 2009 H1N1 pandemic overall did
      not differ significantly from that of seasonal influenza. However, the
      demographics of those at risk of severe illness did differ (affecting children
      and young adults, rather than the very young and the very old). The 2009 H1N1
      pandemic led to rapid implementation of health care initiatives, including the
      provision of critical care services, to limit the effect of the influenza
      outbreak on the community. This review focuses on the critical care response to
      the H1N1 pandemic and examines whether the implementation of critical care
      services as planned a priori matched the reality of the clinical workload and the
      patient burden that transpired during the 2009 H1N1 influenza pandemic.

PMID- 21858746
TI  - Influenza drug resistance.
AB  - Influenza viruses are major human pathogens with a global distribution,
      accounting for more than 500,000 annual deaths worldwide and with considerable
      impact on the quality of life and productivity of the society. Due to the limited
      efficacy of vaccination, antiviral drugs constitute a complementary approach in
      the control and prevention of influenza infections and thus play an important
      role in the management of influenza outbreaks and pandemics. Currently,
      adamantanes and neuraminidase inhibitors (NAIs) are the only two classes of anti
      influenza agents approved for clinical use. However, the worldwide emergence and
      high prevalence of adamantane-resistant virus variants has discouraged the use of
      the former drugs. NAIs have proved to be very effective against influenza A and B
      viruses. Nevertheless, oseltamivir-resistant strains have also been reported
      quite frequently, as in the case of seasonal H1N1 viruses that circulated between
      2007 and 2009. Indeed, the emergence of drug-resistant virus variants is always a
      matter of concern because it could significantly compromise the usefulness of
      such intervention. This highlights the need for continuous monitoring of
      resistance markers, as well as the development of new anti-influenza drugs and
      combination therapies.

PMID- 21858747
TI  - Respiratory syncytial virus infection in adults.
AB  - Respiratory syncytial virus (RSV), an enveloped RNA virus in the Paramyxovirus
      family, is the most important cause of lower respiratory tract infection in
      infants and young children, accounting for ~100,000 pediatric hospitalizations
      and 250 deaths annually in the United States. Despite primarily being recognized
      as a pediatric pathogen, RSV reinfection causes substantial disease in all adult
      populations, including healthy young persons, old and frail individuals, those
      with chronic obstructive pulmonary disease and immunocompromised patients. Most
      illnesses are mild in adults, but significant morbidity and mortality can
      develop. In contrast to infants, diagnosis of RSV infections is difficult due to
      low virus shedding, and optimal diagnosis requires molecular tests.
      Unfortunately, antiviral therapy is of limited benefit. Ribavirin and palivizumab
      are the only approved pharmacological agents for RSV treatment and prophylaxis,
      respectively, and are primarily used in infants; data regarding their usefulness
      in adults are limited. Currently, specific antiviral therapy is generally
      reserved for severely immunocompromised patients or severe respiratory failure.
      The greatest promise for reducing the impact of RSV in adults may be through
      immunization. However, an effective vaccine for RSV is not currently available.

PMID- 21858748
TI  - Update on rhinovirus and coronavirus infections.
AB  - Rhinoviruses and coronaviruses cause significant morbidity in immunocompetent
      people of all ages and in patients with underlying chronic medical or
      immunosuppressed conditions. Newer diagnostic tests, such as polymerase chain
      reaction (PCR), have expanded our understanding of these respiratory viruses in
      clinical infections. These sensitive diagnostic tests have been used to describe
      new members of these virus families, such as human rhinovirus C (HRVC) and human
      coronavirus NL-63 (HCoV-NL63). The epidemiology of these newly described viruses
      will help us develop better intervention strategies.

PMID- 21858749
TI  - Human metapneumovirus.
AB  - Human metapneumovirus (hMPV) is a common pathogen that can cause both upper and
      lower respiratory tract infections, particularly in children, elderly adults, and
      immunocompromised hosts. Since its initial identification in 2001, hMPV has been
      isolated from individuals with acute respiratory tract infections (ARTIs) in
      virtually every continent. Serological studies indicate that it has caused human
      infection since 1958 or earlier. The epidemiology and clinical manifestations of
      hMPV are similar to those of the human respiratory syncytial virus (hRSV). HMPV
      has a seasonal variation: it circulates in late winter to early spring in
      temperate climates; late spring and summer in tropical regions. In young
      children, symptoms range from mild upper respiratory tract infections to severe
      lower respiratory tract infections (eg, bronchiolitis, croup, and pneumonia). In
      adults, hMPV reinfection typically presents with colds and flulike clinical
      manifestations. The disease is more severe (sometimes lethal) in
      immunocompromised hosts. Reverse transcription polymerase chain reaction (RT-PCR)
      is the most sensitive test with which to detect hMPV infection. Direct detection
      of hMPV antigens with an immunofluorescent antibody test is available but is less
      sensitive than PCR. Antibody testing is used mainly for retrospective diagnosis
      (>= fourfold increase in titer or seroconversion) and for epidemiological
      studies. The mainstay of treatment of hMPV infections is supportive. Ribavirin
      has similar activity in vitro and in animal models against hRSV and hMPV, but its
      efficacy in vivo is unproven. Monoclonal antibodies have activity in murine
      models but are not available in humans. Several vaccines are promising in animal
      models, but their safety and efficacy have not yet been evaluated in humans.

PMID- 21858750
TI  - DNA viruses (CMV, EBV, and the herpesviruses).
AB  - The human Herpesviridae family consists of eight members: cytomegalovirus (CMV),
      Epstein-Barr virus (EBV), herpes simplex virus 1 and 2 (HSV-1, -2), varicella
      zoster virus (VZV), and human herpesvirus 6, 7, and 8 (HHV-6, -7, -8). Lifelong
      latency may develop in the host with reactivation during periods of relative
      immunosuppression that occurs in transplant recipients. These are pleiotropic
      viruses: in addition to their direct effects of tissue injury and clinical
      illness, they exhibit several indirect effects, including immunomodulation and
      effects on angiogenesis and tumorigenesis, which may result in long-term adverse
      sequelae in the lung allograft. CMV and HHV-6 and -7 are increasingly recognized
      as major causes of morbidity and mortality in lung transplant recipients. EBV and
      HHV-8 have proven oncogenic potential. HSV-1 and -2 and VZV are neurotropic,
      causing perioral fever blisters, genital ulcerations, and, rarely, encephalitis.
      This article discusses the individual pathogens, preventive strategies in the era
      of potent treatment regimens for established viral infection or disease and their
      potential impact on the indirect effects of these viruses on long-term allograft
      function, and the incidence, risk factors for, and impact of antiviral
      resistance.

PMID- 21858752
TI  - Adenovirus.
AB  - Adenoviruses (AdV) are DNA viruses that typically cause mild infections involving
      the upper or lower respiratory tract, gastrointestinal (GI) tract, or
      conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis,
      hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or encephalitis.
      Adenovirus infections are more common in young children, owing to lack of humoral
      immunity. Epidemics of AdV infections may occur in healthy children or adults in
      closed or crowded settings (particularly military recruits). The disease is more
      severe, and dissemination is more likely in patients with impaired immunity (eg,
      organ transplant recipients, human immunodeficiency virus infection, congenital
      immunodeficiency syndromes). Fatality rates for untreated severe AdV pneumonia or
      disseminated disease may exceed 50%. More than 50 serotypes of AdV have been
      identified. Different serotypes display different tissue trophisms and correlate
      with clinical manifestations of infection. The predominant serotypes differ among
      countries or regions and change over time. Transmission of novel strains between
      countries or across continents and replacement of dominant serotypes by new
      strains may occur. Treatment of AdV infections is controversial because
      prospective, randomized therapeutic trials have not been done. Cidofovir is
      considered the drug of choice for severe AdV infections, but not all patients
      require treatment. Vaccines have been shown to be highly efficacious in reducing
      the risk of respiratory AdV infection but are currently not available.

PMID- 21858753
TI  - Molecular assays for the detection and characterization of respiratory viruses.
AB  - Patient care providers face an enormous challenge in diagnosing vial respiratory
      diseases because of similar clinical manifestations, as well as insensitivity
      and/or slow conventional laboratory detection methods. Nucleic acid-targeted
      molecular assays are playing critical roles in rapid detection, screening, and
      identification of respiratory viral pathogens due to their high sensitivity and
      specificity, short test turnaround time, as well as automatic and high-throughput
      processing. User-developed and commercial molecular methods have gradually been
      developed and become available for detection and identification of common viral
      pathogens causing respiratory tract infections. Incorporated with cutting edge
      techniques, these methods can be used to detect one or more pathogens in a single
      reaction tube qualitatively and quantitatively. Although the molecular assays
      have been increasingly used in the clinical setting, laboratorians and clinicians
      should well know the limitations of these molecular assays to wisely choose the
      right tests and correctly interpret test results.

PMID- 21858751
TI  - Respiratory viral infections in hematopoietic stem cell and solid organ
      transplant recipients.
AB  - Respiratory viral infections (RVIs) are common causes of mild illness in
      immunocompetent children and adults with rare occurrences of significant
      morbidity or mortality. Complications are more common in the very young, very
      old, and those with underlying lung diseases. However, RVIs are increasingly
      recognized as a cause of morbidity and mortality in recipients of hematopoietic
      stem cell transplants (HSCT) and solid organ transplants (SOTs). Diagnostic
      techniques for respiratory syncytial virus (RSV), parainfluenza, influenza, and
      adenovirus have been clinically available for decades, and these infections are
      known to cause serious disease in transplant recipients. Modern molecular
      technology has now made it possible to detect other RVIs including human
      metapneumovirus, coronavirus, and bocavirus, and the role of these viruses in
      causing serious disease in transplant recipients is still being worked out. This
      article reviews the current information regarding epidemiology, pathogenesis,
      clinical presentation, diagnosis, and treatment of these infections, as well as
      the aspects of clinical significance of RVIs unique to HSCT or SOT.

PMID- 21858755
TI  - Metabolomic differentiation of maca (Lepidium meyenii) accessions cultivated
      under different conditions using NMR and chemometric analysis.
AB  - To gain insights on the effects of color type, cultivation history, and growing
      site on the composition alterations of maca (Lepidium meyenii Walpers)
      hypocotyls, NMR profiling combined with chemometric analysis was applied to
      investigate the metabolite variability in different maca accessions. Maca
      hypocotyls with different colors (yellow, pink, violet, and lead-colored)
      cultivated at different geographic sites and different areas were examined for
      differences in metabolite expression. Differentiations of the maca accessions
      grown under the different cultivation conditions were determined by principle
      component analyses (PCAs) which were performed on the datasets derived from their
      1H NMR spectra. A total of 16 metabolites were identified by NMR analysis, and
      the changes in metabolite levels in relation to the color types and growing
      conditions of maca hypocotyls were evaluated using univariate statistical
      analysis. In addition, the changes of the correlation pattern among the
      metabolites identified in the maca accessions planted at the two different sites
      were examined. The results from both multivariate and univariate analysis
      indicated that the planting site was the major determining factor with regards to
      metabolite variations in maca hypocotyls, while the color of maca accession seems
      to be of minor importance in this respect.

PMID- 21858754
TI  - Progress in respiratory virus vaccine development.
AB  - Viral respiratory infections cause significant morbidity and mortality in infants
      and young children as well as in at-risk adults and the elderly. Although many
      viral pathogens are capable of causing respiratory disease, vaccine development
      has to focus on a limited number of pathogens, such as those that commonly cause
      serious lower respiratory illness (LRI). Whereas influenza virus vaccines have
      been available for some time (see the review by Clark and Lynch in this issue),
      vaccines against other medically important viruses such as respiratory syncytial
      virus (RSV), the parainfluenza viruses (PIVs), and metapneumovirus (MPVs) are not
      available. This review aims to provide a brief update on investigational vaccines
      against RSV, the PIVs, and MPV that have been evaluated in clinical trials or are
      currently in clinical development.

PMID- 21858756
TI  - Uncaria rhynchophylla ameliorates cognitive deficits induced by D-galactose in
      mice.
AB  - The stem with hooks of Uncaria rhynchophylla is a component herb of many
      traditional formulae for the treatment of neurodegenerative diseases. However,
      scientific evidence of the efficacy of Uncaria rhynchophylla in the treatment of
      Alzheimer's disease (AD) in animal models is lacking. Thus, in the present study,
      we investigated whether the 70 % aqueous ethanol extract of Uncaria rhynchophylla
      (EUR) could protect against D-galactose (D-gal)-induced cognitive deficits in
      mice. Mice were given a subcutaneous injection of D-gal (50 mg/kg) and orally
      administered EUR (100, 200, or 400 mg/kg) daily for 8 weeks. The effect of EUR on
      D-gal-induced cognitive deficits was evaluated by measuring behavioral and
      neurochemical parameters of AD and the antioxidant status of brain tissue. The
      results showed that EUR (200 or 400 mg/kg) significantly increased exploratory
      behavior (assessed by an open-field test) and improved spatial learning and
      memory function (assessed by the Morris water maze test) in D-gal-treated mice.
      In addition, EUR (200 or 400 mg/kg) significantly increased the levels of
      acetylcholine and glutathione and decreased the activity of acetylcholinesterase
      and the level of malondialdehyde in the brains of D-gal-treated mice. These
      results indicate that EUR ameliorates cognitive deficits induced by D-gal in
      mice, and that this action may be mediated, at least in part, by the inhibition
      of acetylcholinesterase activity and the enhancement of the antioxidant status of
      brain tissue.

PMID- 21858757
TI  - Bioactive isoquinoline alkaloids from Corydalis saxicola.
AB  - Twelve isoquinoline alkaloids including two new nitro-containing
      tetrahydroprotoberberines, (-)-2,9-dihydroxyl-3,11-dimethoxy-1,10
      dinitrotetrahydroprotoberberine (1) and (+)-4-nitroisoapocavidine (2), were
      isolated from the whole plant of Corydalis saxicola Bunting. The structures of
      the new compounds were established by spectroscopic analysis and chemical
      evidence. The inhibitory activity of these isolates against cholinesterase and
      canine parvovirus were evaluated. Compounds 1 and 1A, (+)-1-nitroapocavidine (5),
      berberine (8), palmatine (9), dehydrocavidine (10), and sanguinarine (11) showed
      potent inhibitory activity against acetylcholinesterase with IC(50) values of
      less than 10 uM, while only compound 1 possessed weak activity against canine
      parvovirus. Structure-activity studies demonstrated that the nitro substituents
      at ring A in the tetrahydroprotoberberines led to an increase in the anti
      acetylcholinesterase activity.

PMID- 21858758
TI  - Effects of insulin and St. John's Wort treatments on anxiety, locomotory
      activity, depression, and active learning parameters of streptozotocin-diabetic
      rats.
AB  - The aim of this work was to investigate the effects of St. John's Wort (SJW)
      extract treatment on behavioral changes arising in streptozotocin (STZ)-diabetic
      rats. Plus-maze, activity cage, modified forced swimming, and active avoidance
      tests were performed for evaluating exploratory behaviors, spontaneous locomotor
      activities, depression levels, and learning parameters of animals, respectively.
      Obtained data exhibited a diabetes mellitus (DM)-induced increase in anxiety and
      depression levels, decrease in spontaneous locomotor activities, and impairment
      of learning parameters in rats even in the early stages of the disease. Daily
      insulin replacement (2 IU/kg/day) could not restore these impaired parameters
      completely, indicating the need of novel therapeutic approaches. SJW extract (125
      and 250 mg/kg) treatments for seven days provided significant improvement in all
      of the impaired parameters observed in this study, probably due to its
      antidiabetic and central nervous system (CNS)-related effects. Based on the
      findings of the present study, it may be suggested that SJW extracts may be of
      help to diabetic patients suffering from depressive moods, sleeping disturbances,
      and cognitive deficits and may provide a new potential alternative for the
      treatment of psychiatric complications of diabetes.

PMID- 21858759
TI  - Discovery and identification of 2-phenylethyl 2,6-dihydroxybenzoate as a natural
      lipid-lowering lead.
AB  - Guided by lipid-lowering assays, a new compound (1, 2-phenylethyl 2,6
      dihydroxybenzoate) was isolated from the ethanolic extract of Geophila herbacea.
      The structure of 1 was determined unambiguously by spectral data interpretation
      and confirmed by X-ray crystallographic analysis. Preliminary dose-dependency of
      1 verified its lipid-lowering bioactivity in vitro. A facile chemical synthesis
      for 1 was performed to provide a practical approach for further studies on
      structure-activity relationship.

PMID- 21858760
TI  - [Image findings in Von Meyenburg Complexes].

PMID- 21858761
TI  - The role of angiogenic growth factors in organogenesis.
AB  - Angiogenic growth factors are a class of molecules which exert a fundamental role
      in the process of blood vessel formation. Besides vasculogenic and angiogenic
      properties, these compounds mediate a complex series of patterning activities
      during organogenesis. Angiogenic factors cooperate in the growth and development
      of embryo tissues in a cross-talk between endothelial cells and tissue cells. It
      is well established that many tissue-derived factors are involved in blood vessel
      formation, but there is now emerging evidence that angiogenic factors and
      endothelial cells themselves represent a crucial source of instructive signals to
      non-vascular tissue cells during organ development. Thus, angiogenic factors and
      endothelial cell signalling are currently believed to provide fundamental cues
      for cell fate specification, embryo patterning, organ differentiation and
      postnatal tissue remodelling. This review article will summarize some of the
      recent advances in our understanding of the role of angiogenic factors and
      endothelial cells as effectors in organ formation.

PMID- 21858762
TI  - A brief history of angiogenesis assays.
AB  - The major problem with angiogenesis research is the choice of an appropriate
      assay. Currently, many in vitro and in vivo techniques are available for research
      into the functions of endothelial cells during angiogenesis. In this historical
      review article, we describe and evaluate the methodology and specific features of
      some of the most frequently used of these assays.

PMID- 21858763
TI  - From the discovery of vascular endothelial growth factor to the introduction of
      avastin in clinical trials - an interview with Napoleone Ferrara by Domenico
      Ribatti.
AB  - Napoleone Ferrara and his colleagues at Genentech were the first to isolate and
      clone vascular endothelial growth factor (VEGF) in 1989. His laboratory has
      investigated many aspects of VEGF biochemistry and molecular biology. In 1993,
      Ferrara reported that inhibition of VEGF-induced angiogenesis by specific
      monoclonal antibodies resulted in dramatic suppression of the growth of a variety
      of tumors in vivo. These findings provided an important evidence that inhibition
      of angiogenesis may suppress tumor growth and blocking VEGF action could have
      therapeutic value for a variety of malignancies. A further development was the
      design in a rational fashion in 1997 of a humanized anti-VEGF monoclonal antibody
      (Avastin), now in clinical trials as a treatment for several solid tumors and
      also outside of cancer, in the treatment of age-related macular degeneration
      (AMD). Ferrara's work is revolutionizing quality of life for many of the
      estimated 1.2 million individuals in the US who have wet AMD. Upwards of a
      million AMD patients worldwide have already received anti-VEGF antibody therapy.

PMID- 21858764
TI  - Fifteen years of molecular lymphangiogenesis - an interview with Kari Alitalo by
      Tatiana Petrova.
AB  - Kari Alitalo is one of the leaders in the field of lymphangiogenesis. Research
      from his laboratory has contributed to the transformation of a largely
      descriptive field into a dynamic discipline, which now holds promise for the
      treatment of cancer, inflammation and vascular dysfunction. The interview intends
      to provide historical insights into these changes and hopefully inspiration to
      the young generation of vascular biologists.

PMID- 21858765
TI  - Anti-angiogenesis in cancer; met and unmet goals - an interview with Robert
      Kerbel by Francesco Bertolini.
AB  - Robert Kerbel is one of the most influential scientists in the field of cancer
      related angiogenesis and anti-angiogenic therapies. Along with the late Judah
      Folkman, Dr. Kerbel has also pioneered the use of continuous low dose
      chemotherapy for cancer treatment, an approach which is now widely used for many
      types of cancer and is a promising backbone to be associated with novel targeted
      therapies. In this interview, Dr. Kerbel describes the steps that moved his
      career towards the angiogenesis field, the already achieved biological and
      clinical results and the unmet goals.

PMID- 21858767
TI  - The role of blood flow and microRNAs in blood vessel development.
AB  - The circulatory system is the first organ system that develops during
      embryogenesis, and is essential for embryo viability and survival. Crucial for
      developing a functional vasculature are the specification of arterial-venous
      identity in vessels and the formation of a hierarchical branched vascular
      network. Sprouting angiogenesis, intussusception, and flow driven remodeling
      events collectively contribute to establishing the vascular architecture. At the
      molecular level, arterial-venous identity and branching are regulated by
      genetically hardwired mechanisms involving Notch, vascular endothelial growth
      factor and neural guidance molecule signaling pathways, modulated by hemodynamic
      factors. MicroRNAs are small, non-coding RNAs that act as silencers to fine-tune
      the gene expression profile. MicroRNAs are known to influence cell fate
      decisions, and microRNA expression can be controlled by blood flow, thus placing
      microRNAs potentially at the center of the genetic cascades regulating vascular
      differentiation. In the present review, we summarize current progress regarding
      microRNA functions in blood vessel development with an emphasis on studies
      performed in zebrafish and mouse models.

PMID- 21858766
TI  - Modeling of angioadaptation: insights for vascular development.
AB  - Vascular beds are generated by vasculogenesis and sprouting angiogenesis, and
      these processes have strong stochastic components. As a result, vascular patterns
      exhibit significant heterogeneity with respect to the topological arrangement of
      the individual vessel segments and the characteristics (length, number of
      segments) of different arterio-venous pathways. This structural heterogeneity
      tends to cause heterogeneous distributions of flow and oxygen availability in
      tissue. However, these quantities must be maintained within tolerable ranges to
      allow normal tissue function. This is achieved largely through adjustment of
      vascular flow resistance by control of vessel diameters. While short-term
      diameter control by changes in vascular tone in arterioles and small arteries
      plays an important role, in the long term an even more important role is played
      by structural adaptation (angioadaptation), occurring in response to metabolic
      and hemodynamic signals. The effectiveness, stability and robustness of this
      angioadaptation depend sensitively on the nature and strength of the vascular
      responses involved and their interactions with the network structure.
      Mathematical models are helpful in understanding these complex interactions, and
      can be used to simulate the consequences of failures in sensing or signal
      transmission mechanisms. For the tumor microcirculation, this strategy of
      combining experimental observations with theoretical models, has led to the
      hypothesis that dysfunctional information transport via vascular connexins is a
      major cause of the observed vascular pathology and increased heterogeneity in
      oxygen distribution.

PMID- 21858768
TI  - Hemangiomas - current therapeutic strategies.
AB  - Hemangiomas are benign neoplasms of the vasculature frequently encountered in
      children. Several studies have shown that these tumors are characterized by
      excessive angiogenesis. Although benign, the lesions can present with
      complications, and may thus require treatment. There are multiple therapeutic
      options available for patients with problematic or life threatening hemangiomas,
      some of which have serious side effects. Randomized clinical trials and evidence
      based studies on the efficacy of these treatments is still lacking. The
      recognition that excessive angiogenesis underlies hemangiogenesis offers an
      opportunity for the development of safer therapeutic strategies that are based on
      the inhibition of angiogenesis. We review medical therapies currently employed in
      the management of hemangiomas and the role of angiogenesis inhibition in
      hemangioma therapy.

PMID- 21858769
TI  - Nervous vascular parallels: axon guidance and beyond.
AB  - The vascular and nervous systems are organized with well defined and accurate
      networks, which represent the anatomical structure enabling their functions. In
      recent years, it has been clearly demonstrated that these two systems share in
      common several mechanisms and specificities. For instance, the networking
      properties of the nervous and vascular systems are governed by common cues that
      in the brain regulate axon connections and in the vasculature remodel the
      primitive plexus towards the vascular tree. Here, we summarize the role of
      semaphorins as a paradigmatic example of the role of axon guidance molecules in
      physiological and pathological angiogenesis. Finally, we discuss the presence in
      blood vessels of neurexin and neuroligin, two proteins that finely modulate
      synaptic activity in the brain. This observation is suggestive of an intriguing
      new class of molecular and functional parallels between neurons and vascular
      cells.

PMID- 21858770
TI  - Paracrine regulation of angiogenesis by different cell types in the aorta ring
      model.
AB  - The development of blood vessels during angiogenesis is the result of paracrine
      interactions between tube-forming endothelial cells and angiogenic factor
      producing nonendothelial cells. This process can be reproduced and studied under
      chemically defined culture conditions by culturing vascular explants in three
      dimensional gels of extracellular matrix. Rings of rat or mouse aorta cultured in
      collagen, fibrin or basement membrane gels produce angiogenic outgrowths composed
      of a mixed population of endothelial cells and nonendothelial cells. Aortic
      angiogenesis is regulated by endogenous angiogenic factors, inflammatory
      cytokines, chemokines, extracellular matrix molecules, and proteolytic enzymes
      produced by cells of the vessel wall in response to the injury of the dissection
      procedure. In this paper, we review how macrophages, mural cells and fibroblasts
      regulate different stages of the angiogenic process, from the formation of
      immature endothelial sprouts to the reabsorption of the neovessels. We also
      describe how aortic cultures can be used to study interactions between angiogenic
      outgrowths and nonvascular cell types such as bone marrow macrophages, platelets
      or cancer cells. Morphologic, genetic and functional studies of this model have
      provided invaluable information on how vessels form, mature, interact with
      nonvascular cell types, and are eventually reabsorbed. Further analysis of the
      paracrine cross-talk between aortic endothelial and nonendothelial cells is
      likely to provide new insights into the angiogenic process and its key
      mechanisms.

PMID- 21858771
TI  - Role of laminins in physiological and pathological angiogenesis.
AB  - The interaction of endothelial cells and pericytes with their microenvironment,
      in particular with the basement membrane, plays a crucial role during
      vasculogenesis and angiogenesis. In this review, we focus on laminins, a major
      family of extracellular matrix molecules present in basement membranes. Laminins
      interact with cell surface receptors to trigger intracellular signalling that
      shapes cell behaviour. Each laminin exerts a distinct effect on endothelial cells
      and pericytes which largely depends on the adhesion receptor profile expressed on
      the cell surface. Moreover, proteolytic cleavage of laminins may affect their
      role in angiogenesis. We report in vitro and in vivo data on laminin-111, -411, 
      511 and -332 and their associated signalling that regulates cell behaviour and
      angiogenesis under normal and pathological conditions. We also discuss how tissue
      specific deletion of laminin genes affects the behaviour of endothelial cells and
      pericytes and thus angiogenesis. Finally, we examine how coculture systems with
      defined laminin expression contribute to our understanding of the roles of
      laminins in normal and pathological vasculogenesis and angiogenesis.

PMID- 21858772
TI  - Molecular mechanisms of lymphangiogenesis in development and cancer.
AB  - The lymphatic system, also named the second vascular system, plays a critical
      role in tissue homeostasis and immunosurveillance. The past two decades of
      intensive research have led to the identification and detailed understanding of
      many molecular players and mechanisms regulating the formation of the lymphatic
      vasculature during embryonic development. Furthermore, clinical and experimental
      data clearly demonstrate that the formation of new lymphatic vessels by sprouting
      lymphangiogenesis from pre-existing lymphatic vessels, or by the de novo
      formation of lymphatic capillaries also occurs in various pathological
      conditions, such as cancer and organ transplant rejection, while
      lymphangiogenesis is non-functional in primary edema. In cancer, lymphatic
      vessels are one major gateway for invasive tumor cells to leave the primary tumor
      site and to establish distant organ metastasis. Therefore, the specific targeting
      of the lymphatic vasculature at the tumor site could be a promising approach to
      prevent metastasis formation.

PMID- 21858773
TI  - Zebrafish embryo, a tool to study tumor angiogenesis.
AB  - Zebrafish (Danio rerio) represents a powerful model system in cancer research.
      Recent observations have shown the possibility to exploit zebrafish to
      investigate tumor angiogenesis, a pivotal step in cancer progression and target
      for anti-tumor therapies. Experimental models have been established in zebrafish
      adults, juveniles, and embryos, each one with its own advantages and
      disadvantages. Novel genetic tools and high resolution in vivo imaging techniques
      are also becoming available in zebrafish. It is anticipated that zebrafish will
      represent an important tool for chemical discovery and gene targeting in tumor
      angiogenesis. This review focuses on the recently developed tumor angiogenesis
      models in zebrafish, with particular emphasis to tumor engrafting in zebrafish
      embryos.

PMID- 21858774
TI  - Tumor blood vessel visualization.
AB  - Significant advances have been made in understanding the role of tumor
      angiogenesis and its influence on tumor progression in cancer. Based on this
      knowledge, a series of inhibitors of angiogenesis have been developed and
      evaluated in preclinical and clinical trials. Since detailed information of tumor
      progression in response to therapy is important to assess the efficacy of anti
      tumor treatment in vivo, noninvasive imaging techniques emerge more and more as
      important tools to monitor alterations in tumor growth and vessel recruitment, as
      well as metastatic spread over time. So far, remarkable efforts have been made to
      improve the technical capability of these imaging modalities based on better
      resolution, as well as to implement multimodal approaches combining molecular
      with anatomical information. Advanced imaging techniques not only allow the
      detection and monitoring of tumor development, but also facilitate a broad
      understanding of the cellular and molecular events that propagate tumor
      angiogenesis, as well as those occurring in response to therapy. This review
      provides an overview of different imaging techniques in preclinical settings of
      oncological research and discusses their potential impact on clinical
      translation. Imaging modalities will be presented that have been implemented to
      address key biological issues by exploring tumor angiogenic processes and
      evaluating antiangiogenic therapy.

PMID- 21858775
TI  - The use of the orthotopic model to validate antivascular therapies for cancer.
AB  - The orthotopic model reproduces aspects of the tumour microenvironment and
      emulates a number of important biological features of cancer progression,
      angiogenesis, metastasis and resistance. Due to its parallels with human cancer,
      the model can be used to evaluate therapeutic responses to various therapies.
      This review outlines the importance of using the orthotopic implantation of
      tumour cells in mice models for evaluating the effectiveness of antivascular
      therapies.

PMID- 21858776
TI  - Antiangiogenic cancer therapy: why do mouse and human patients respond in a
      different way to the same drug?
AB  - The tumor vasculature is an increasingly attractive target for development of
      anticancer drugs. The fundamental principle for antiangiogenic cancer therapy is
      based on the inhibitory effect of chemical compounds, proteins or nucleotides on
      tumor angiogenesis. Indeed, in almost all preclinical tumor models,
      antiangiogenic monotherapy with different agents shows potent effects on
      suppression of tumor growth. However, antiangiogenic monotherapy has barely
      produced any clinical benefits in cancer patients. Although in combination with
      chemotherapy some antiangiogenic drugs demonstrate survival improvement in
      patients with certain types of cancers, the overall benefits by addition of
      antiangiogenic drugs (ADs) to chemotherapy remain modest. The disparity of AD
      responses between preclinical models and clinical cancer patients has raised
      important issues, which include: 1) Are current animal tumor models appropriate
      for assessing the therapeutic efficacy of ADs for clinical development? 2) What
      are the key differences between mouse tumor models and human cancer patients? 3)
      Are anti-VEGF drugs off target in cancer patients? 4) What are alternative
      options for improvement of the clinical benefits of ADs? In this short review, I
      discuss these critical issues in relation to the clinical practice of ADs.

PMID- 21858777
TI  - Escape mechanisms after antiangiogenic treatment, or why are the tumors growing
      again?
AB  - Inhibitors of angiogenesis and radiation induce compensatory changes in the tumor
      vasculature both during and after cessation of treatment. In numerous preclinical
      studies, angiogenesis inhibitors were shown to be efficient in the treatment of
      many pathological conditions, including solid cancers. In most clinical trials,
      however, this approach turned out to have no significant effect, especially if
      applied as monotherapy. Recovery of tumors after therapy is a major problem in
      the management of cancer patients. The mechanisms underlying tumor recovery (or
      therapy resistance) have not yet been explicitly elucidated. This review deals
      with the transient switch from sprouting to intussusceptive angiogenesis, which
      may be an adaptive response of tumor vasculature to cancer therapy that allows
      the vasculature to maintain its functional properties. Potential candidates for
      molecular targeting of this angioadaptive mechanism are yet to be elucidated in
      order to improve the currently poor efficacy of contemporary antiangiogenic
      therapies.

PMID- 21858778
TI  - Predicting the open conformations of protein kinases using molecular dynamics
      simulations.
AB  - Protein kinases (PK) control phosphorylation in eukaryotic cells, and thereby
      regulate metabolic pathways, cell cycle progression, apoptosis, and
      transcription. Consequently, there is significant interest in manipulating PK
      activity and treat diseases by using small-molecule drugs. All PK catalytic
      domains undergo large conformational changes as a result of substrate binding and
      phosphorylation. The "closed" state of a PK catalytic domain is the only state
      able to phosphorylate the target substrate, which makes the two other observed
      states (the "open" and the "intermediate" states) interesting drug targets. We
      investigate whether molecular dynamics (MD) simulations starting from the closed
      state of the catalytic domain of protein kinase A (C-PKA) can be used to produce
      realistic structures representing the intermediate and/or open conformation of C
      PKA, because this would allow for drug docking calculations and drug design using
      MD snapshots. We perform 36 ten-nanosecond MD simulations starting from the
      closed conformation [PDB ID: ATP] of C-PKA in various liganded and phosphorylated
      states. The results show that MD simulations are capable of reproducing the open
      conformation of C-PKA with good accuracy within 1 ns of simulation as measured by
      Calpha root mean square deviations (RMSDs) and RMSDs of atoms defining the ATP
      binding pocket. Importantly, we are able to show that even without knowledge of
      the structure of the open form of C-PKA, we can identify the MD snapshots
      resembling the open conformation most using the open structure of a different PK
      displaying only 23% sequence identity to C-PKA.

PMID- 21858780
TI  - Intramolecular C---H...O hydrogen-bond mediated stabilization of a cis-DPro imide
      bond in a stereocontrolled heterochiral model peptide.
AB  - The X-ray diffraction analysis of a stereocontrolled heterochiral designed model
      peptide Boc-(D) Pro-Thr-OMe (1) revealed the existence of an unusual folded
      molecular structure, stabilized via an effective unconventional C---H...O type
      intramolecular hydrogen-bond, encompassing a noncovalent 12-membered ring-motif.
      Together with an uncommon type a disposition of the urethane moiety, the tightly
      folded topology is compounded with a cis-(D) Pro imide-bond. The overall
      conformation is suggested to be the reminiscent of specific type VI beta-turn
      structures, hitherto, characterized across the Aaa-cis-Pro peptide-bonds in
      globular proteins and polypeptides. The (13) C NMR spectrum of 1 in an apolar
      CDCl(3) environment revealed the presence of approximately an equal population of
      cis and trans isomers unexpectedly, analogous to Pro side-chain, the (13) C NMR
      chemical-shifts of Thr C(beta) -resonance is observed to be sensitive toward cis
      trans isomerization. In conjunction with solid-state FT-IR spectral data, we
      established that a network of complex intermolecular hydrogen-bonds stabilize a
      self-complementary noncovalent helical hexagonal self-assembly and
      crystallographic supramolecular aggregate. The results incline us to highlight
      that the stabilization of cis-(D) Pro peptide-bond in crystalline state may be
      driven by the favorable energy of formation of an unconventional weak C---H...O
      intramolecular hydrogen-bond.

PMID- 21858779
TI  - Comparison of solution conformations and stabilities of modified helix 69 rRNA
      analogs from bacteria and human.
AB  - The helix 69 (H69) region of the large subunit (28S) ribosomal RNA (rRNA) of Homo
      sapiens contains five pseudouridine (Psi) residues out of 19 total nucleotides,
      three of which are highly conserved. In this study, the effects of this abundant
      modified nucleotide on the structure and stability of H69 were compared with
      those of uridine in double-stranded (stem) regions. These results were compared
      with previous hairpin (stem plus single-stranded loop) studies to understand the
      contributions of the loop sequences to H69 structure and stability. The role of a
      loop nucleotide substitution from an A in bacteria (position 1918 in Escherichia
      coli 23S rRNA) to a G in eukaryotes (position 3734 in H. sapiens 28S rRNA) was
      examined. Thermodynamic parameters for the duplex RNAs were obtained through UV
      melting studies, and differences in the modified and unmodified RNA structures
      were examined by circular dichroism spectroscopy. The overall folded structure of
      human H69 appears to be similar to the bacterial RNA, consistent with the idea
      that ribosome structure and function are highly conserved; however, our results
      reveal subtle differences in structure and stability between the bacterial and
      human H69 RNAs in both the stem and loop regions. These findings may be
      significant with respect to H69 as a potential drug target site.

PMID- 21858781
TI  - Effects of copolypeptides on amyloid fibrillation of hen egg-white lysozyme.
AB  - The fibrillation of hen egg-white lysozyme (HEWL) in the absence and presence of
      simple, unstructured D,L-lysine-co-glycine (D,L-Lys-co-gly) and D,L-lysine-co-L
      phenylalanine (D,L-Lys-co-Phe) copolypeptides was studied by using a variety of
      analytical techniques. The attenuating and decelerating effects on fibrillation
      are significantly dependent on the polypeptide concentration and the composition
      ratios in the polypeptide chain. Interestingly, D,L-Lys-co-gly and D,L-Lys-co-Phe
      copolypeptides with the same composition ratio have comparable attenuating
      effects on fibrillation. The copolypeptide with highest molar fraction of glycine
      residue exhibits the strongest suppression of HEWL fibrillation. The
      copolypeptide has the highest hydrophobic interacting capacity due to the more
      molar ratio of apolar monomer in the polymer backbone. The major driving forces
      for the association of HEWL and copolypeptides are likely to be hydrogen bonding
      and hydrophobic interactions, and these interactions reduce the concentration of
      free protein in solution available to proceed to fibrillation, leading to the
      increase of lag time and attenuation of fibrillation. The results of this work
      may contribute to the understanding of the molecular factors affecting amyloid
      fibrillation and the molecular mechanism(s) of the interactions between the
      unstructured polypeptides and the amyloid proteins.

PMID- 21858782
TI  - Polyethylene glycol behaves like weak organic solvent.
AB  - Effect of polyethylene glycol (PEG) on protein solubility has been primarily
      ascribed to its large hydrodynamic size and thereby molecular crowding effect.
      However, PEG also shows characteristics of organic solvents. Here, we have
      examined the solubility of glycine and aliphatic and aromatic amino acids in PEG
      solutions. PEG400, PEG4000, and PEG20000 decreased the solubility of glycine,
      though to a much smaller magnitude than the level achieved by typical organic
      solvents, including ethanol and dimethyl sulfoxide. PEG4000 showed varying degree
      of interactions with amino acid side chains. The free energy of aliphatic side
      chains marginally increased by the addition of PEG4000, indicating their weak
      unfavorable interactions. However, it significantly decreased the free energy of
      the aromatic side chains and hence stabilized them. Thus, it was concluded that
      PEG behaves like weak organic solvents; namely PEG destabilized (interacted
      unfavorably with) polar and charged groups and stabilized (interacted favorably
      with) aromatic groups. Interestingly, the interaction of PEG20000, but neither
      PEG400 nor PEG4000, with glycine resulted in phase separation under the saturated
      concentration of glycine.

PMID- 21858783
TI  - Controlling the dimensions of amyloid fibrils: toward homogenous components for
      bionanotechnology.
AB  - Amyloid fibrils have been recognized as having potential in a variety of
      bionanotechnological applications. However, realization of these applications is
      constrained by a lack of control over morphology and alignment, both crucial for
      potential end uses. This article focuses on the use of growth and storage
      conditions to control the length of amyloid fibrils formed from bovine insulin,
      with length distributions constructed from transmission electron microscopy (TEM)
      images. Growth temperature, pH, protein concentration, and storage conditions
      were examined and were seen to offer a range of conditions that favor different
      length distribution. The use of amyloid fibrils as nanowires is one area where
      control of fibril dimensions is desirable, for experimental setup and endpoint
      applications. The conductive properties of fibrils formed from bovine insulin are
      presented, with these insulin fibrils being shown to have high resistivity in
      their unmodified state, with current values in the nanoamp range. These low
      current values can be increased via modification, or the fibrils used in their
      native state in applications where low current values are desirable. These
      findings, coupled with the ability to predict and select for various insulin
      amyloid fibril dimensions, enhances their utility as nanomaterials.

PMID- 21858784
TI  - Transient hydrogen bonding in uniformly 13C,15N-labeled carbohydrates in water.
AB  - We report NMR studies of transient hydrogen bonding in a polysaccharide (PS)
      dissolved in water without cosolvent at ambient temperature. The PS portion of
      the Escherichia coli O142 lipopolysaccharide is comprised of repeating
      pentasaccharide units of GalNAc (N-acetyl galactosamine), GlcNAc (N-acetyl
      glucosamine), and rhamnose in a 3:1:1 ratio, respectively. A 105-ns molecular
      dynamics (MD) simulation on one pentasaccharide repeat unit predicts transient
      inter-residue hydrogen bonds from the GalNAc NH groups in the PS. To investigate
      these predictions experimentally, the PS was uniformly 13C,15N enriched and the
      NH, carbonyl, C2, C4, and methyl resonances of the GalNAc and GlcNAc residues
      assigned using through-bond triple-resonance NMR experiments. Temperature
      dependence of amide NH chemical shifts and one-bond NH J couplings support that
      NH groups on two of the GalNAc residues are donors in transient hydrogen bonds.
      The remaining GalNAc and GlcNAc NHs do not appear to be donors from either
      temperature-dependent chemical shifts or one-bond NH J couplings. These results
      substantiate the presence of weak or partial hydrogen bonds in carbohydrates, and
      that MD simulations of repeating units in PSs provide insight into overall PS
      structure and dynamics.

PMID- 21858785
TI  - Quantitative analysis of the fermentative metabolism of glycerol in Escherichia
      coli.
AB  - Availability, low price, and high degree of reduction have made glycerol a highly
      attractive and exploited carbon source for the production of fuels and reduced
      chemicals. Here we report the quantitative analysis of the fermentative
      metabolism of glycerol in Escherichia coli through the use of kinetic modeling
      and metabolic control analysis (MCA) to gain a better understanding of glycerol
      fermentation and identify key targets for genetic manipulation that could enhance
      product synthesis. The kinetics of glycerol fermentation in a batch culture was
      simulated using a dynamic model consisting of mass balances for glycerol,
      ethanol, biomass, and 11 intracellular metabolites, along with the corresponding
      kinetic expressions for the metabolism of each species. The model was then used
      to calculate metabolic control coefficients and elucidate the control structure
      of the pathways involved in glycerol utilization and ethanol synthesis. The
      calculated flux control coefficients indicate that the glycolytic flux during
      glycerol fermentation is almost exclusively controlled by the enzymes glycerol
      dehydrogenase (encoded by gldA) and dihydroxyacetone kinase (DHAK) (encoded by
      dhaKLM). In agreement with the MCA findings, overexpression of gldA and dhaKLM
      led to significant increase in glycerol utilization and ethanol synthesis fluxes.
      Moreover, overexpression of other enzymes involved in the pathways that mediate
      glycerol utilization and its conversion to ethanol had no significant impact on
      glycerol utilization and ethanol synthesis, further validating the MCA
      predictions. These findings were then applied as a means of increasing the
      production of ethanol: overexpression of glycerol dehyrdogenase and DHAK enabled
      the production of 20 g/L ethanol from crude glycerol, a by-product of biodiesel
      production, indicating the potential for industrial scale conversion of waste
      glycerol to ethanol under anaerobic conditions.

PMID- 21858786
TI  - Validation of long-term primary neuronal cultures and network activity through
      the integration of reversibly bonded microbioreactors and MEA substrates.
AB  - In vitro recording of neuronal electrical activity is a widely used technique to
      understand brain functions and to study the effect of drugs on the central
      nervous system. The integration of microfluidic devices with microelectrode
      arrays (MEAs) enables the recording of networks activity in a controlled
      microenvironment. In this work, an integrated microfluidic system for neuronal
      cultures was developed, reversibly coupling a PDMS microfluidic device with a
      commercial flat MEA through magnetic forces. Neurons from mouse embryos were
      cultured in a 100 um channel and their activity was followed up to 18 days in
      vitro. The maturation of the networks and their morphological and functional
      characteristics were comparable with those of networks cultured in macro
      environments and described in literature. In this work, we successfully
      demonstrated the ability of long-term culturing of primary neuronal cells in a
      reversible bonded microfluidic device (based on magnetism) that will be
      fundamental for neuropharmacological studies.

PMID- 21858787
TI  - Synthesis of FAEEs from glycerol in engineered Saccharomyces cerevisiae using
      endogenously produced ethanol by heterologous expression of an unspecific
      bacterial acyltransferase.
AB  - The high price of petroleum-based diesel fuel has led to the development of
      alternative fuels, such as ethanol. Saccharomyces cerevisiae was metabolically
      engineered to utilize glycerol as a substrate for ethanol production. For the
      synthesis of fatty acid ethyl esters (FAEEs) by engineered S. cerevisiae that
      utilize glycerol as substrate, heterologous expression of an unspecific
      acyltransferase from Acinetobacter baylyi with glycerol utilizing genes was
      established. As a result, the engineered YPH499 (pGcyaDak, pGupWs-DgaTCas) strain
      produced 0.24 g/L FAEEs using endogenous ethanol produced from glycerol. And this
      study also demonstrated the possibility of increasing FAEE production by
      enhancing ethanol production by minimizing the synthesis of glycerol. The overall
      FAEE production in strain YPH499 fps1Delta gpd2Delta (pGcyaDak, pGupWs-DgaTCas)
      was 2.1-fold more than in YPH499 (pGcyaDak, pGupWs-DgaTCas), with approximately
      0.52 g/L FAEEs produced, while nearly 17 g/L of glycerol was consumed. These
      results clearly indicated that FAEEs were synthesized in engineered S. cerevisiae
      by esterifying exogenous fatty acids with endogenously produced ethanol from
      glycerol. This microbial system acts as a platform in applying metabolic
      engineering that allows the production of FAEEs from cheap and abundant
      substrates specifically glycerol through the use of endogenous bioethanol.

PMID- 21858788
TI  - Putting cells under pressure: a simple and efficient way to enhance the
      productivity of medium-chain-length polyhydroxyalkanoate in processes with
      Pseudomonas putida KT2440.
AB  - The success of bioprocess implementation relies on the ability to achieve high
      volumetric productivities and requires working with high-cell-density
      cultivations. Elevated atmospheric pressure might constitute a promising tool for
      enhancing the oxygen transfer rate (OTR), the major growth-limiting factor for
      such cultivations. However, elevated pressure and its effects on the cellular
      environment also represent a potential source of stress for bacteria and may have
      negative effects on product formation. In order to determine whether elevated
      pressure can be applied for enhancing productivity in the case of medium-chain
      length polyhydroxyalkanoate (mcl-PHA) production by Pseudomonas putida KT2440,
      the impact of a pressure of 7 bar on the cell physiology was assessed. It was
      established that cell growth was not inhibited by this pressure if dissolved
      oxygen tension (DOT) and dissolved carbon dioxide tension (DCT) were kept below
      ~30 and ~90 mg L(-1), respectively. Remarkably, a little increase of mcl-PHA
      volumetric productivity was observed under elevated pressure. Furthermore, the
      effect of DCT, which can reach substantial levels during high-cell-density
      processes run under elevated pressure, was investigated on cell physiology. A
      negative effect on product formation could be dismissed since no significant
      reduction of mcl-PHA content occurred up to a DCT of ~540 mg L(-1). However,
      specific growth rate exhibited a significant decrease, indicating that successful
      high-cell-density processes under elevated pressure would be restricted to
      chemostats with low dilution rates and fed-batches with a small growth rate
      imposed during the final part. This study revealed that elevated pressure is an
      adequate and efficient way to enhance OTR and mcl-PHA productivity. We estimate
      that the oxygen provided to the culture broth under elevated pressure would be
      sufficient to triple mcl-PHA productivity in our chemostat system from 3.4 (at 1
      bar) to 11 g L(-1)h(-1) (at 3.2 bar).

PMID- 21858789
TI  - Self-expanding metallic stents for large bowel obstruction.
AB  - BACKGROUND: Self-expanding metallic stents (SEMS) may relieve colonic obstruction
      as definitive therapy or as a bridge to elective surgery. METHODS: This was a
      retrospective longitudinal cohort study of patients undergoing insertion of SEMS
      for large bowel obstruction at one institution. Scrutiny of the radiology
      department's coding system allowed identification of all patients undergoing
      colonic stent insertion between 2002 and 2008. Data were extracted from patient
      case notes and investigation reports. RESULTS: Eighty-two patients with a median
      age of 75 (interquartile range (i.q.r.) 43-94) years underwent stent insertion,
      71 for palliation and 11 as a bridge to surgery. Obstruction was due to malignant
      disease in 67 patients and had a benign cause in 15. Median survival in the
      palliative setting was 103 (i.q.r. 44-317) days. Complications occurred in 43
      patients, of whom 22 underwent unplanned surgery. High-grade obstruction
      (relative risk (RR) 2.05; P = 0.055) and benign disease (RR 3.45; P < 0.001) were
      associated with risk of adverse events. CONCLUSION: SEMS should not be used for
      large bowel obstruction with benign pathology.

PMID- 21858790
TI  - Survival and prognostic factors in patients with small bowel carcinoid tumour.
AB  - BACKGROUND: Previous studies of small bowel carcinoid tumours usually presented
      overall or relative survival. This study, in addition, evaluated disease-specific
      survival in a cohort of patients in a geographically defined population. METHODS:
      Patients diagnosed with carcinoid of the jejunum or ileum in Jonkoping County
      between 1960 and 2005 were eligible for inclusion. Available tumour specimens
      were re-examined to confirm the diagnosis. Medical records and pathology reports
      were reviewed in detail. RESULTS: A total of 145 patients were included in the
      study. One hundred and thirty-five patients underwent surgery in connection with
      the diagnosis. Resection was considered complete (R0) in 74 patients (54.8 per
      cent). Only two localized tumours recurred, whereas no patient with distant
      metastases was cured. Patients with regional metastases who underwent R0
      resection had a better survival than patients with incomplete resection (P =
      0.005), and a majority of patients remained recurrence-free. Median overall
      survival was 7.2 years and median disease-specific survival 12.3 years. In
      multivariable analysis, age 61-74 years (hazard ratio (HR) 3.78, 95 per cent
      confidence interval 1.86 to 7.68), age 75 years or more (HR 3.96, 1.79 to 8.74),
      distant metastases (HR 14.44, 1.59 to 131.36) and incomplete tumour resection (HR
      2.71, 1.11 to 6.61) were associated with worse disease-specific survival. Later
      time period of diagnosis (HR 0.45, 0.24 to 0.84) was associated with better
      disease-specific survival. CONCLUSION: Age, disease stage and complete resection
      were identified as independent prognostic factors for survival in patients with
      small bowel carcinoid tumours. The importance of achieving R0 resection is
      therefore emphasized.

PMID- 21858791
TI  - Impact of breast surgery on survival in women presenting with metastatic breast
      cancer.
AB  - BACKGROUND: Advanced breast cancer is common in less affluent parts of Asia. The
      impact of breast surgery on survival of women presenting with metastatic breast
      cancer in this setting was investigated. METHODS: Women presenting with
      metastatic breast cancer at the initial diagnosis at the University Malaya
      Medical Centre (Malaysia) between 1993 and 2008 were included in the study.
      Mortality of patients who had primary breast surgery was compared with that of
      those without surgery, and adjusted for possible confounders by means of a
      propensity score. RESULTS: Of 3689 patients, 375 (10.2 per cent) presented with
      metastatic disease. One hundred and thirty-nine patients (37.1 per cent)
      underwent surgery. A total of 330 deaths occurred during 6814 person-months of
      follow-up. The 2-year survival rate was 21.2 (95 per cent confidence interval
      (c.i.) 15.9 to 26.5) per cent in women who did not have surgery and 46.3 (37.7 to
      54.9) per cent in those who had breast surgery. Breast surgery was associated
      with a 28 per cent lower risk of death (hazard ratio 0.72, 95 per cent c.i. 0.56
      to 0.94), after adjustment for patient and tumour characteristics, metastatic
      profile and treatment. CONCLUSION: Surgical resection of the primary breast
      tumour was independently associated with a survival advantage in patients
      presenting with metastatic breast cancer.

PMID- 21858792
TI  - Amputations in patients with diabetes.

PMID- 21858793
TI  - Oncologic emergencies: Pathophysiology, presentation, diagnosis, and treatment.
AB  - Oncologic emergencies can occur at any time during the course of a malignancy,
      from the presenting symptom to end-stage disease. Although some of these
      conditions are related to cancer therapy, they are by no means confined to the
      period of initial diagnosis and active treatment. In the setting of recurrent
      malignancy, these events can occur years after the surveillance of a cancer
      patient has been appropriately transferred from a medical oncologist to a primary
      care provider. As such, awareness of a patient's cancer history and its possible
      complications forms an important part of any clinician's knowledge base. Prompt
      identification of and intervention in these emergencies can prolong survival and
      improve quality of life, even in the setting of terminal illness. This article
      reviews hypercalcemia, hyponatremia, hypoglycemia, tumor lysis syndrome, cardiac
      tamponade, superior vena cava syndrome, neutropenic fever, spinal cord
      compression, increased intracranial pressure, seizures, hyperviscosity syndrome,
      leukostasis, and airway obstruction in patients with malignancies.
      Chemotherapeutic emergencies are also addressed.

PMID- 21858795
TI  - Organizations join forces to confront global cancer crisis: UN meeting this month
      will focus on strategies to combat cancer in developing countries.

PMID- 21858797
TI  - New technology shows genetic differences in cancer patients.

PMID- 21858798
TI  - Following cancer prevention guidelines may lower risk of death from all causes.

PMID- 21858794
TI  - Genetics, genomics, and cancer risk assessment: State of the Art and Future
      Directions in the Era of Personalized Medicine.
AB  - Scientific and technologic advances are revolutionizing our approach to genetic
      cancer risk assessment, cancer screening and prevention, and targeted therapy,
      fulfilling the promise of personalized medicine. In this monograph, we review the
      evolution of scientific discovery in cancer genetics and genomics, and describe
      current approaches, benefits, and barriers to the translation of this information
      to the practice of preventive medicine. Summaries of known hereditary cancer
      syndromes and highly penetrant genes are provided and contrasted with recently
      discovered genomic variants associated with modest increases in cancer risk. We
      describe the scope of knowledge, tools, and expertise required for the
      translation of complex genetic and genomic test information into clinical
      practice. The challenges of genomic counseling include the need for genetics and
      genomics professional education and multidisciplinary team training, the need for
      evidence-based information regarding the clinical utility of testing for genomic
      variants, the potential dangers posed by premature marketing of first-generation
      genomic profiles, and the need for new clinical models to improve access to and
      responsible communication of complex disease risk information. We conclude that
      given the experiences and lessons learned in the genetics era, the
      multidisciplinary model of genetic cancer risk assessment and management will
      serve as a solid foundation to support the integration of personalized genomic
      information into the practice of cancer medicine.

PMID- 21858799
TI  - Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall
      cell lung cancer.
AB  - Currently, nonsmall-cell lung cancer (NSCLC) is the leading cause of cancer
      related death in the United States. Angiogenesis, the formation of new
      vasculature, is a complex and tightly regulated process that promotes metastasis
      and disease progression in lung cancer and other malignancies. Developmental
      antiangiogenic agents have shown activity in NSCLC, and bevacizumab, an
      antiangiogenic monoclonal antibody, is approved for the treatment of patients
      with advanced disease. However, predictive biomarkers are needed to guide the
      administration of antiangiogenic agents. It is possible that angiogenic molecules
      could accurately predict patient response to targeted antiangiogenic therapies,
      which would allow individualized and perhaps more effective treatment. Angiogenic
      signaling molecules may also have value as prognostic indicators, which may be
      useful for the management of NSCLC. Here the author provides an overview of
      angiogenic molecules currently being investigated as prognostic biomarkers in
      NSCLC and discusses their potential to guide treatment choices.

PMID- 21858800
TI  - Is the N1c category of the new American Joint Committee on cancer staging system
      applicable to patients with rectal cancer who receive preoperative
      chemoradiotherapy?
AB  - BACKGROUND: Pericolorectal tumor deposits (TDs) are associated with adverse
      outcomes in patients with colorectal cancer, and the seventh edition of the
      American Joint Committee on Cancer (AJCC) staging system recently classified TDs
      without regional lymph node metastasis as category N1c. However, the definition
      of TDs has varied. Moreover, with the recent, widespread application of
      preoperative chemoradiotherapy (CRT) in rectal cancers, residual primary tumor
      confined to the mesorectum is not infrequent, and it is unclear whether the N1c
      category is appropriate for these tumors. METHODS: To evaluate the prognostic
      significance of the N1c classification in patients with rectal cancers after
      preoperative CRT, the authors reviewed the histologic features of 136 rectal
      cancers that were classified previously with a tumor classification of 3 [T3],
      negative lymph nodes [N0], and no metastasis [M0] based on the pathologic extent
      of disease (ypT3N0M0). These tumors were reclassified according to the new AJCC
      staging system, and patient outcomes were analyzed. RESULTS: Perirectal TDs were
      detected in 16 of 136 patients (11.8%). Patterns of TD included a separate nodule
      pattern in 6 patients (38%), a perivascular pattern in 4 patients (25%), a
      perineural pattern in 4 patients (25%), and a lymphatic pattern in 2 patients
      (12%). By using the new N1c category, 120 patients (88.2%) were classified with
      yp-stage IIA disease, 6 patients (4.4%) were classified with yp-stage IIIA
      disease, and 10 patients (7.4%) were classified with yp-stage IIIB disease.
      Kaplan-Meier survival analysis indicated that there were no significant
      differences between the TD-positive and TD-negative groups in disease-free
      survival (DFS) or overall survival (OS) (P = .48 for both; log-rank test). In
      addition, the reclassified TMN stage was not related to DFS (P = .17) or OS (P =
      .072). CONCLUSIONS: The category N1c may not be appropriate for patients with
      rectal cancer after preoperative CRT, because the definition of ypN1c was
      confusing and did not have prognostic significance.

PMID- 21858801
TI  - Assessing the impact of comorbid illnesses on death within 10 years in prostate
      cancer treatment candidates.
AB  - BACKGROUND: Treatment choice in prostate cancer is influenced by pre-existing
      comorbid illnesses, but information about their individual prognostic impact is
      sparse, and only 1 comorbidity index has been developed for this setting. The
      authors assessed the impact of individual comorbid illnesses on the risk of
      early, other-cause death in prostate cancer treatment candidates and propose a
      modification of an existing comorbidity scale. METHODS: A population-based case
      cohort study included patients diagnosed from 1990 through 1998 in Ontario,
      Canada who had planned curative radiotherapy or prostatectomy. The subcohort
      numbered 1643, and the case sample (those dying of other causes within 10 years)
      numbered 630. Ontario Cancer Registry data were linked to data from medical
      charts, including: age, comorbidity using the Cumulative Illness Rating Scale for
      Geriatrics (CIRS-G), stage, prostate-specific antigen, Gleason score, and
      treatment. Cox proportional hazards regression assessed the age-adjusted
      association between CIRS-G and other-cause death. RESULTS: Respiratory and
      cardiac diseases were the most common comorbidities and most strongly associated
      with an increased risk of death. Other important comorbidities included vascular
      disease, renal disease, and diabetes. The modified CIRS-G(pros) score yielded a
      relative risk (RR) of 1.64 (95% confidence interval [CI], 1.52-1.76) for those
      scoring 1 compared with 0 and RR 1.18 (95% CI, 1.15-1.21) for each increment
      above 1. Except for those aged >80 years, results were consistent across
      treatment type and age group. CONCLUSIONS: This study provides estimates of the
      role of individual comorbid illnesses in prostate cancer. The modified CIRS
      G(pros) could be useful in the clinic and in future research on this patient
      population.

PMID- 21858802
TI  - Treatment with lenalidomide modulates T-cell immunophenotype and cytokine
      production in patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: Lenalidomide, an immunomodulatory agent, has activity in
      lymphoproliferative disorders. The authors, therefore, evaluated its effects on T
      cell immunophenotype and cytokine production in patients with chronic lymphocytic
      leukemia (CLL). METHODS: To study the immunomodulatory effects of lenalidomide in
      CLL, the authors recruited 24 patients with untreated CLL enrolled in a phase 2
      clinical trial of lenalidomide and obtained peripheral blood specimens for
      immunologic studies consisting of enumeration of T cells and assessing their
      ability to synthesize cytokines after activation through T-cell receptor (TCR).
      RESULTS: After 3 cycles of therapy, patients had a significant reduction in
      percentage (%) and absolute lymphocyte count (ALC) and an increase in percentage
      of T cells, percentage of activated CD8(+) T cells producing IFN-gamma, and
      percentage of regulatory T (T(R) ) cells when compared with their respective
      levels before treatment. After 15 cycles of treatment, responder patients had
      significant reduction in percentage of lymphocytes and ALC, percentage of
      activated CD4(+) T cells producing IL-2, IFN-gamma, or TNF-alpha, and percentage
      of T(R) cells when compared with their perspective levels after 3 cycles of
      treatment. Furthermore, the numbers of activated CD4(+) T cells producing IL-2,
      IFN-gamma, or TNF-alpha, activated CD8(+) T cells producing IFN-gamma, and T(R)
      cells normalized to the range of healthy subjects. CONCLUSIONS: Treatment with
      lenalidomide resulted in the normalization of functional T-cell subsets in
      responders, suggesting that lenalidomide may modulate cell-mediated immunity in
      patients with CLL.

PMID- 21858804
TI  - A functional single nucleotide polymorphism at the promoter region of cyclin A2
      is associated with increased risk of colon, liver, and lung cancers.
AB  - BACKGROUND: The objective of this was to identify functional single nucleotide
      polymorphisms (SNPs) in cyclin-dependent kinases (CDKs) and cyclins that are
      associated with risk of human cancer. METHODS: First, 45 SNPs in CDKs and cyclins
      were analyzed in 106 lung cancers and 108 controls for a pilot study. One SNP
      (reference SNP [rs] 769236, +1 guanine to adenine [G->A]) at the promoter region
      of cyclin A2 (CCNA2) also was analyzed in 1989 cancers (300 breast cancers, 450
      colorectal cancers, 450 gastric cancers, 367 hepatocellular carcinomas, and 422
      lung cancers) and in 1096 controls. Genotyping was performed using matrix
      assisted laser desorption-ionization/time-of-flight mass spectrometry.
      Transcriptional activity of the SNP according to the cell cycle was analyzed by
      using a luciferase reporter assay and fluorescence-activated cell sorting
      analysis in NIH3T3 cells. RESULTS: In the pilot study, the SNP (rs769236) was
      associated significantly with the risk of lung cancer. In the expanded study,
      multivariate logistic regression indicated that the AA homozygous variant of the
      SNP was associated significantly with the development of lung cancer (P < .0001;
      codominant model), colorectal cancer (P < .0001), and hepatocellular carcinoma (P
      = .02) but not with breast cancer or gastric cancer. The luciferase activity of a
      300-base pair construct that contained the A allele was 1.5-fold greater than the
      activity of a construct with the G allele in NIH3T3 cells. The high luciferase
      activity of constructs that contained the A allele did not change with cell cycle
      progression. CONCLUSIONS: The current results suggested that an SNP (rs769236) at
      the promoter of CCNA2 may be associated significantly with increased risk of
      colon, liver, and lung cancers.

PMID- 21858803
TI  - Circulating endothelial progenitors and CXCR4-positive circulating endothelial
      cells are predictive markers for bevacizumab.
AB  - BACKGROUND: Bevacizumab plus chemotherapy is a standard option in the treatment
      of metastatic colorectal cancer (mCRC). The aim of this study was to investigate
      the potential of circulating endothelial cell progenitors (CEPs) and phenotypical
      circulating endothelial cells (CECs) as surrogate markers of clinical outcome in
      mCRC patients to identify responders to bevacizumab in combination with
      chemotherapy. METHODS: A total of 69 patients with measurable mCRC were enrolled
      in this prospective study. Whole blood samples were analyzed before initiation of
      treatment and on days 4 and 14. Phenotypical CECs and CEPs were then isolated and
      enumerated by using flow cytometry. RESULTS: CEP levels of less than 0.04% on day
      4 were significantly associated with longer progression-free survival (PFS) and
      overall survival (OS) (P < .001, P = .002, respectively) as compared with levels
      of 0.04% or more. In addition, CXCR4-positive CEC levels of less than 20% at
      baseline were significantly associated with longer PFS and OS as compared other
      indicators investigated (P < .001, P = .002, respectively). CONCLUSIONS: Levels
      of CEPs on day 4 and proportion of CXCR4-positive CECs at baseline were
      correlated with the prognosis of bevacizumab combination chemotherapy, suggesting
      that these surrogate markers may play a core role in the selection of candidates
      for bevacizumab treatment.

PMID- 21858805
TI  - Detection of circulating Bmi-1 mRNA in plasma and its potential diagnostic and
      prognostic value for uterine cervical cancer.
AB  - Bmi-1 is overexpressed in uterine cervical cancer (UCC) and is found to be
      associated with adverse clinical characteristics and poor prognosis. However,
      little information is available on the status of circulating Bmi-1 mRNA in UCC.
      Because circulating cell-free nucleic acids have emerged as a novel class of
      markers for cancer detection, our research aims to address this question by
      detecting the circulating Bmi-1 mRNA and to assess its diagnostic and prognostic
      potential in UCC. Reverse transcription quantitative real-time PCR method was
      established to detect the circulating Bmi-1 mRNA in plasma of 109 patients with
      UCC, 138 patients with cervical intraepithelial neoplasia (CIN) and 80 healthy
      volunteers, and found that it was significantly increased in UCC compared with
      CINs and healthy controls (all at p < 0.001). Moreover, its high level was
      significantly correlated with advanced clinical stage (p < 0.001) and positive
      lymph nodes metastasis (p = 0.002). The area under the receiver operating
      characteristic curve (AUC) was 0.881, and the optimal cut-off value was 0.057,
      providing a sensitivity of 69.7% and a specificity of 95.9%. The AUC for
      circulating Bmi-1 mRNA showed higher diagnosis capability than that for SCC-Ag (p
      = 0.035) or CA125 (p < 0.001) currently utilized. Kaplan-Meier analysis
      demonstrated a correlation between increased circulating Bmi-1 mRNA level and
      reduced disease-free survival (DFS) (p = 0.001) and overall survival (OS) (p =
      0.015). And, Cox analysis indicated that it was an independent prognostic factor
      for DFS and OS. We conclude that circulating Bmi-1 mRNA may be a potential
      noninvasive molecular marker for diagnosis and prognosis of UCC.

PMID- 21858806
TI  - The intrinsic fusogenicity of glioma cells as a factor of transformation and
      progression in the tumor microenvironment.
AB  - We have previously reported in vitro heterotypic fusion of glioma cells with
      neural progenitor cells, producing tetraploid cells expressing genetic
      complements of each partner. Herein, we investigated the fusogenicity of glioma
      cells. In 1:1 cocultures of single-labeled cells, U87MG cells presented high
      frequency of homotypic fusogenic events, producing cells that coexpressed both
      fluorescent proteins. Six percent of the total cells had 8n DNA content,
      consistent with the finding that the double-labeled cells were actively
      proliferating. In coculture with fibroblasts, glioma cell fusogenicity resulted
      in viable reprogrammed cells, thus emerging as a plausible source of tumor cell
      heterogeneity. As for heterotypic fusion to happen, glioma cells have to
      establish direct contact with other cells, the effect of stroma on glioma cells
      was analyzed. Proliferation assays and array analysis of cancer-related pathways
      established a promalignant effect of stroma. This effect was mediated by
      fibronectin and was nearly completely abolished by inhibitors of the epidermal
      growth-factor receptor. That stroma elicited transduction signaling through the
      mitogen-activated-protein kinase/extracellular-signal-regulated kinase pathway,
      which is linked to increased tumor cell migration through extracellular matrix,
      suggested that glioma cells may actively approach nontumor cells in stromal
      niches. According to these results, the fusogenicity of glioma cells emerged as
      an inherent factor for phenotypic changes leading to glioma progression.

PMID- 21858808
TI  - Biomarkers of oxidant load and type-specific clearance of prevalent oncogenic
      human papillomavirus infection: markers of immune response?
AB  - Human papillomavirus (HPV) infection is the cause of cervical cancer. Increased
      production of reactive oxygen species (ROS) maybe the common mechanism through
      which HPV-cofactors (i.e., smoking and inflammation) influence duration of
      infections. Biomarkers of total oxidant load may serve as cumulative measures of
      ROS exposure due to these cofactors. Therefore, we conducted a study evaluating
      the association between biomarkers of oxidant load and duration of HPV
      infections, early HPV natural history events. Serum samples were obtained from
      444 HPV-positive women in the Ludwig-McGill Cohort Study. Anti-5-hydroxymethyl-2'
      deoxyuridine autoantibody (anti-HMdU aAb) and malondialdehyde (MDA) were measured
      at baseline. Cox-proportional hazard models were used to estimate the probability
      of clearing any HPV, oncogenic HPV, non-oncogenic HPV and HPV-16 infections.
      Women with elevated MDA were significantly more likely to clear prevalent
      oncogenic HPV infections compared to those with lower MDA levels (Adjusted Hazard
      Ratio (AHR) = 2.7; 95%CI = 1.4-5.1). There did not appear to be an association
      between elevated MDA and clearance of incident oncogenic HPV infections.
      Similarly, women with elevated anti-HMdU aAb levels had higher rates of prevalent
      oncogenic HPV infection clearance (Quartile 3:AHR = 2.2; 95%CI = 1.2-4.4;
      Quartile 4:AHR = 2.4; 95%CI = 1.2-4.9). Higher levels of oxidant load biomarkers
      were associated with increased clearance of prevalent HPV infections. However,
      oxidant load biomarkers measured before incident infections were not associated,
      suggesting that the elevation of MDA and anti-HMdU aAb may reflect an ongoing
      effective immune response, such as increased innate immunity. More research
      focused on the immune responses to HPV and elevated markers of oxidant load is
      needed.

PMID- 21858809
TI  - Meta-analysis of gene expression profiles associated with histological
      classification and survival in 829 ovarian cancer samples.
AB  - Transcriptomic analysis of global gene expression in ovarian carcinoma can
      identify dysregulated genes capable to serve as molecular markers for histology
      subtypes and survival. The aim of our study was to validate previous candidate
      signatures in an independent setting and to identify single genes capable to
      serve as biomarkers for ovarian cancer progression. As several datasets are
      available in the GEO today, we were able to perform a true meta-analysis. First,
      829 samples (11 datasets) were downloaded, and the predictive power of 16
      previously published gene sets was assessed. Of these, eight were capable to
      discriminate histology subtypes, and none was capable to predict survival. To
      overcome the differences in previous studies, we used the 829 samples to identify
      new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free
      survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction
      (RT-PCR) analysis for the best 40 genes associated with histology subtypes and
      survival. Over 90% of subtype-associated genes were confirmed. Overall survival
      was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8.
      Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully
      validated several gene sets in a meta-analysis in large datasets of ovarian
      samples. Additionally, several individual genes identified were validated in a
      clinical cohort.

PMID- 21858807
TI  - Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women
      aged 15-25 years with and without serological evidence of previous exposure to
      HPV-16/18.
AB  - In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)
      16/18 AS04-adjuvanted vaccine (Cervarix((r)), GlaxoSmithKline Biologicals) was
      highly efficacious against HPV-16/18 infections and precancerous lesions in women
      HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline.
      We present further data on vaccine efficacy (VE) against HPV-16/18 in the total
      vaccinated cohort including women who may have been exposed to HPV-16/18
      infection before vaccination. In women with no evidence of current or previous
      HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1%
      confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9%
      (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3
      98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment
      algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence
      of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against
      6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+
      [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV
      16/18 infection (DNA negative), regardless of their baseline HPV-16/18
      serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6
      94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when
      using TAA]. In women who were DNA positive for one vaccine type, the vaccine was
      efficacious against the other vaccine type. The vaccine did not impact the
      outcome of HPV-16/18 infections present at the time of vaccination. Vaccination
      was generally well tolerated regardless of the woman's HPV-16/18 DNA or
      serological status at entry.

PMID- 21858810
TI  - Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority
      of vaccinated cancer patients.
AB  - CD4(+)  T cells have been shown to be crucial for the induction and maintenance
      of cytotoxic T cell responses and to be also capable of mediating direct tumor
      rejection. Therefore, the anticancer therapeutic efficacy of peptide-based
      vaccines may be improved by addition of HLA class II epitopes to stimulate T
      helper cells. Survivin is an apoptosis inhibiting protein frequently
      overexpressed in tumors. Here we describe the first immunological evaluation of a
      survivin-derived CD4(+)  T cell epitope in a multipeptide immunotherapy trial for
      prostate carcinoma patients. The survivin peptide is promiscuously presented by
      several human HLA-DRB1 molecules and, most importantly, is naturally processed by
      dendritic cells. In vaccinated patients, it was able to induce frequent, robust
      and multifunctional CD4(+)  T cell responses, as monitored by IFN-gamma ELISPOT
      and intracellular cytokine staining. Thus, this HLA-DR restricted epitope is
      broadly immunogenic and should be valuable for stimulating T helper cells in
      patients suffering from a wide range of tumors.

PMID- 21858811
TI  - IL-13 regulates cancer invasion and metastasis through IL-13Ralpha2 via ERK/AP-1
      pathway in mouse model of human ovarian cancer.
AB  - Previously, we have demonstrated that a variety of human cancers including the
      ovarian cancer express IL-13Ralpha2, a high affinity receptor for IL-13. Herein,
      we have examined if IL-13 regulates invasion and metastasis of ovarian cancer
      through IL-13Ralpha2 in vitro and in vivo in animal models of human ovarian
      cancer. We tested cell invasion and protease activity in IL-13Ralpha2
      overexpressing and IL-13Ralpha2-negative ovarian tumor cell lines. IL-13
      treatment significantly augmented both cell invasion and enzyme activities in
      only IL-13Ralpha2-positive cells but not in IL-13Ralpha2-negative cells in vitro.
      Mechanistically, IL-13 enhanced ERK1/2, AP-1 and MMP activities only in IL
      13Ralpha2-positive cells but not in IL-13Ralpha2-negative cells. In contrast,
      other signaling pathways such as IRS1/2, PI3K and AKT do not seem to be involved
      in IL-13 induced signaling in ovarian cancer cell lines. Highly specific
      inhibitors for MMP and AP-1 efficiently inhibited both invasion and protease
      activities without impacting the basal level invasion and protease activities in
      vitro. In orthotopic animal model of human ovarian cancer, IL-13Ralpha2-positive
      tumors metastasized to lymph nodes and peritoneum earlier than IL-13Ralpha2
      negative tumors. Interestingly, the IL-13Ralpha2-positive tumor bearing mice died
      earlier than mice with IL-13Ralpha2-negative tumor. Intraperitoneal injection of
      IL-13 further shortened survival of IL-13Ralpha2-positive tumor bearing mice
      compared to IL-13Ralpha2-negative tumor mice. IL-13Ralpha2-positive tumors and
      lymph node metastasis expressed higher levels of MMPs and higher ERK1/2
      activation compared to IL-13Ralpha2-negative tumors. Taken together, IL-13Ralpha2
      is involved in cancer metastasis through activation of ERK/AP-1 and that
      targeting IL-13Ralpha2 might not only directly kill primary tumors but also
      prevent cancer metastasis.

PMID- 21858812
TI  - Inhibition of autophagy potentiates the antitumor effect of the multikinase
      inhibitor sorafenib in hepatocellular carcinoma.
AB  - Multikinase inhibitor sorafenib inhibits proliferation and angiogenesis of tumors
      by suppressing the Raf/MEK/ERK signaling pathway and VEGF receptor tyrosine
      kinase. It significantly prolongs median survival of patients with advanced
      hepatocellular carcinoma (HCC) but the response is disease-stabilizing and
      cytostatic rather than one of tumor regression. To examine the mechanisms
      underlying the relative resistance in HCC, we investigated the role of autophagy,
      an evolutionarily conserved self-digestion pathway, in hepatoma cells in vitro
      and in vivo. Sorafenib treatment led to accumulation of autophagosomes as
      evidenced by conversion from LC3-I to LC3-II observed by immunoblot in Huh7, HLF
      and PLC/PRF/5 cells. This induction was due to activation of autophagic flux, as
      there was further increase in LC3-II expression upon treatment with lysosomal
      inhibitors, clear decline of the autophagy substrate p62, and an mRFP-GFP-LC3
      fluorescence change in sorafenib-treated hepatoma cells. Sorafenib inhibited the
      mammalian target of rapamycin complex 1 and its inhibition led to accumulation of
      LC3-II. Pharmacological inhibition of autophagic flux by chloroquine increased
      apoptosis and decreased cell viability in hepatoma cells. siRNA-mediated
      knockdown of the ATG7 gene also sensitized hepatoma cells to sorafenib. Finally,
      sorafenib induced autophagy in Huh7 xenograft tumors in nude mice and
      coadministration with chloroquine significantly suppressed tumor growth compared
      with sorafenib alone. In conclusion, sorafenib administration induced
      autophagosome formation and enhanced autophagic activity, which conferred a
      survival advantage to hepatoma cells. Concomitant inhibition of autophagy may be
      an attractive strategy for unlocking the antitumor potential of sorafenib in HCC.

PMID- 21858813
TI  - HLA-G expression is associated with metastasis and poor survival in the Balb/c
      nu/nu murine tumor model with ovarian cancer.
AB  - Aberrant HLA-G expression is associated with tumor invasiveness and poor clinical
      prognosis; however, there is a lack of preclinical animal model to address
      whether HLA-G plays a causal role in the unfavorable prognosis of malignancies.
      In the current study, ovarian carcinoma cell lines (HO-8910 and Ovcar-3) were
      transfected with HLA-G gene. HLA-G expression was analyzed with western blot and
      flow cytometry. Transwell experiment was performed to analyze the cell migration
      and invasion capability and/or multicellular spheroid formation was investigated
      with the 3D culture assay in vitro. The effects of HLA-G expression for tumor
      cell organ metastasis and for mouse survival was analyzed with the Balb/c nu/nu
      mouse model. Our data showed that HO-8910-G and Ovcar-3-G cells are of higher
      invasion potential compared with the parental HO-8910 and Ovcar-3 cells.
      Multicellular spheroid formation exists only in HO-8910-G cells in a 3D culture
      assay. In Balb/c nu/nu mouse model, widespread metastasis was observed in mice
      xenografted with HO-8910-G cells, but not in the group with parental cells. Mouse
      survival was dramatically decreased in HO-8910-G and Ovcar-3-G xenografted mice
      than that with HO-8910 and Ovcar-3 cells, respectively. In summary, our study
      provided the first evidence that HLA-G expression is associated with tumor
      metastasis and with poor survival in an animal model with ovarian cancer.

PMID- 21858814
TI  - ABO blood group, hepatitis B viral infection and risk of pancreatic cancer.
AB  - Little is known about the role of association between ABO blood type and risk of
      pancreatic cancer develops through effects on hepatitis B viral (HBV) infection.
      Our study aimed to determine whether joint ABO blood type and HBV infection could
      increase the risk for pancreatic cancer. A total of 645 patients with pancreatic
      adenocarcinoma and 711 age- and sex-matched individuals who had nonmalignant
      diseases treated at the Sun Yat-sen University Cancer Center in China were
      retrospectively analyzed. Blood samples were tested for ABO blood type and
      hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs),
      hepatitis B e antigen (HBeAg), hepatitis B e antibody (anti-HBe) and hepatitis B
      core antibody (anti-HBc). Multivariable unconditional logistic regression
      analysis was used to estimate adjusted odds ratios [AORs] and 95% confidence
      interval [CI]. Multivariable analysis with adjustment for risk factors showed
      that A blood type, HBsAg-positive/anti-HBc-positive, anti-HBs-positive/anti-HBc
      positive were significantly associated with pancreatic cancer. The estimated AORs
      (95% CI) were as follows: A blood type, 1.425 (1.071-1.894), HBsAg-positive/anti
      HBc-positive, 1.610 (1.125-2.304), anti-HBs-positive/anti-HBc-positive, 1.526
      (1.159-2.011). The effect of A blood type significantly modified the risk of
      pancreatic cancer among subjects with anti-HBc-positive (AORs = 1.882, 95% CI,
      1.284-2.760). In our study, we reported an association between A blood type,
      infection with HBV and pancreatic cancer risk. Moreover, we found a synergism
      between A blood type and HBV infection in the development of pancreatic cancer.

PMID- 21858815
TI  - ALCAM (CD166) expression and serum levels are markers for poor survival of
      esophageal cancer patients.
AB  - The expression of the activated leukocyte cell adhesion molecule (ALCAM and
      CD166) is increased in various types of cancer. We aimed to evaluate its role as
      a prognostic marker for esophageal cancer (EC). We retrospectively analyzed ALCAM
      expression in 299 primary lesions, 147 lymph node and 46 distant metastases from
      EC patients, on a tissue microarray using immunohistochemistry. Bone marrow
      samples from representative cancer patients (n = 16), taken before primary
      surgery, were stained by double-immunofluorescence for ALCAM and cytokeratins
      (CK). Blood serum samples from 236 cancer patients and 127 controls were analyzed
      for serum ALCAM (s-ALCAM) by ELISA. The immunohistochemical analysis showed
      increased ALCAM expression in the majority of lesions (primary tumor 71%, lymph
      node 76% and distant metastases 80%). ALCAM expression was not associated with
      histopathological parameters except for tumor grading (p = 0.015). ALCAM-positive
      patients had significantly worse recurrence-free and overall survival (OS; p =
      0.002). Disseminated tumor cells (DTC) in bone marrow showed two phenotypes,
      ALCAM+/CK+ (36%) and ALCAM-/CK+ (64%). Multivariate analysis revealed that ALCAM
      expression and elevated s-ALCAM serum values are powerful prognostic variables
      for OS in patients with EC (hazard ratio [HR] 3.987, 95% confidence interval
      [95%CI] 1.906-8.340, p < 0.001 and HR 1.915, 95%CI 1.021-3.592, p = 0.043). The
      results of our study provide preliminary evidence for the potential clinical
      utility of ALCAM as a prognostic biomarker for EC, which might be a basis for
      future clinical application. In addition, ALCAM expression in a subset of DTC of
      the bone marrow indicates a potential function in the metastatic cascade of EC.

PMID- 21858816
TI  - Goodbye to Edward G. (Ted) Jones, MD, DPhil, 1939-2011.

PMID- 21858817
TI  - Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization
      and colocalization with the metabotropic glutamate receptor 5 in the striatum.
AB  - The adenosine A(2A) receptor (A(2A) R) is a potential drug target for the
      treatment of Parkinson's disease and other neurological disorders. In rodents,
      the therapeutic efficacy of A(2A) R modulation is improved by concomitant
      modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the
      anatomical substrate(s) through which these therapeutic benefits could be
      mediated, pre-embedding electron microscopy immunohistochemistry was used to
      conduct a detailed, quantitative ultrastructural analysis of A(2A) R localization
      in the primate basal ganglia and to assess the degree of A(2A) R/mGluR5
      colocalization in the striatum. A(2A) R immunoreactivity was found at the highest
      levels in the striatum and external globus pallidus (GPe). However, the monkey,
      but not the rat, substantia nigra pars reticulata (SNr) also harbored a
      significant level of neuropil A(2A) R immunoreactivity. At the electron
      microscopic level, striatal A(2A) R labeling was most commonly localized in
      postsynaptic elements (58% +/- 3% of labeled elements), whereas, in the GPe and
      SNr, the labeling was mainly presynaptic (71% +/- 5%) or glial (27% +/- 6%). In
      both striatal and pallidal structures, putative inhibitory and excitatory
      terminals displayed A(2A) R immunoreactivity. Striatal A(2A) R/mGluR5
      colocalization was commonly found; 60-70% of A(2A) R-immunoreactive dendrites or
      spines in the monkey striatum coexpress mGluR5. These findings provide the first
      detailed account of the ultrastructural localization of A(2A) R in the primate
      basal ganglia and demonstrate that A(2A) R and mGluR5 are located to interact
      functionally in dendrites and spines of striatal neurons. Together, these data
      foster a deeper understanding of the substrates through which A(2A) R could
      regulate primate basal ganglia function and potentially mediate its therapeutic
      effects in parkinsonism.

PMID- 21858818
TI  - Trigeminal and telencephalic projections to jaw and other upper vocal tract
      premotor neurons in songbirds: sensorimotor circuitry for beak movements during
      singing.
AB  - During singing in songbirds, the extent of beak opening, like the extent of mouth
      opening in human singers, is partially correlated with the fundamental frequency
      of the sounds emitted. Since song in songbirds is under the control of "the song
      system" (a collection of interconnected forebrain nuclei dedicated to the
      learning and production of song), it might be expected that beak movements during
      singing would also be controlled by this system. However, direct neural
      connections between the telencephalic output of the song system and beak muscle
      motor neurons in the brainstem are conspicuous by their absence, leaving
      unresolved the question of how beak movements are affected during singing. By
      using standard tract tracing methods, we sought to answer this question by
      defining beak premotor neurons and examining their afferent projections. In the
      caudal medulla, jaw premotor cell bodies were located adjacent to the terminal
      field of the output of the song system, into which many premotor neurons extended
      their dendrites. The premotor neurons also received a novel input from the
      trigeminal ganglion and an overlapping input from a lateral arcopallial component
      of a trigeminal sensorimotor circuit that traverses the forebrain. The ganglionic
      input in songbirds, which is not present in doves and pigeons that vocalize with
      a closed beak, may modulate the activity of beak premotor neurons in concert with
      the output of the song system. These inputs to jaw premotor neurons could,
      together, affect beak movements as a means of modulating filter properties of the
      upper vocal tract during singing.

PMID- 21858820
TI  - Heterogeneity in dendritic morphology of moth antennal lobe projection neurons.
AB  - A population of projection neurons (PNs) in the antennal lobe (AL) integrates
      sensory information from the antenna and is essential for processing odor
      information in the insect brain. We examined the anatomy of this neuronal
      population in the brain of the silkmoth Bombyx mori. Using intracellular dye
      injection, we labeled a total of 246 PNs and systematically analyzed their
      morphological features, including the soma position, antennocerebral tract, and
      number of innervating glomeruli. For example, we analyzed PNs that had somata in
      the different cell clusters, innervated overlapping but different groups of
      glomeruli, and ran through different pathways. We also identified glomeruli
      innervated by PNs using a previously established procedure that first classifies
      glomeruli into regional groups and then identifies individual glomeruli. We
      analyzed uniglomerular PNs (75.6% of the total) and found heterogeneity in the
      dendritic morphology of the PNs that was dependent on the regions and/or the
      innervating glomeruli. For example, most PNs innervating the macroglomerular
      complex did not have extraglomerular processes, whereas most PNs innervating
      ordinary glomeruli did. Moreover, PNs innervating the toroid glomerulus showed
      heterogeneity in their dendritic morphology. These PNs had dendritic arborization
      in different areas within the glomerulus. We found that, in some cases, the
      innervation pattern of the PN dendrite correlated with individual variation in
      the glomerular organization. These results indicate that PNs are not homogeneous
      populations, and in some cases morphological heterogeneity in PNs correlated with
      change in glomerular organization in the silkmoth AL.

PMID- 21858819
TI  - Reelin demarcates a subset of pre-Botzinger complex neurons in adult rat.
AB  - Identification of two markers of neurons in the pre-Botzinger complex (pre-BotC),
      the neurokinin 1 receptor (NK1R) and somatostatin (Sst) peptide, has been of
      great utility in understanding the essential role of the pre-BotC in breathing.
      Recently, the transcription factor dbx1 was identified as a critical, but
      transient, determinant of glutamatergic pre-BotC neurons. Here, to identify
      additional markers, we constructed and screened a single-cell subtractive cDNA
      library from pre-BotC inspiratory neurons. We identified the glycoprotein reelin
      as a potentially useful marker, because it is expressed in distinct populations
      of pre-BotC and inspiratory bulbospinal ventral respiratory group (ibsVRG)
      neurons. Reelin ibsVRG neurons were larger (27.1 +/- 3.8 MUm in diameter) and
      located more caudally (>12.8 mm caudal to Bregma) than reelin pre-BotC neurons
      (15.5 +/- 2.4 MUm in diameter, <12.8 mm rostral to Bregma). Pre-BotC reelin
      neurons coexpress NK1R and Sst. Reelin neurons were also found in the
      parahypoglossal and dorsal parafacial regions, pontine respiratory group, and
      ventromedial medulla. Reelin-deficient (Reeler) mice exhibited impaired respones
      to hypoxia compared with littermate controls. We suggest that reelin is a useful
      molecular marker for pre-BotC neurons in adult rodents and may play a functional
      role in pre-BotC microcircuits.

PMID- 21858821
TI  - Sacral neural crest-derived cells enter the aganglionic colon of Ednrb-/- mice
      along extrinsic nerve fibers.
AB  - Both vagal and sacral neural crest cells contribute to the enteric nervous system
      in the hindgut. Because it is difficult to visualize sacral crest cells
      independently of vagal crest, the nature and extent of the sacral crest
      contribution to the enteric nervous system are not well established in rodents.
      To overcome this problem we generated mice in which only the fluorescent protein
      labeled sacral crest are present in the terminal colon. We found that sacral
      crest cells were associated with extrinsic nerve fibers. We investigated the
      source, time of appearance, and characteristics of the extrinsic nerve fibers
      found in the aganglionic colon. We observed that the pelvic ganglion neurons
      contributed a number of extrinsic fibers that travel within the hindgut between
      circular and longitudinal muscles and within the submucosa and serosa. Sacral
      crest-derived cells along these fibers diminished in number from fetal to
      postnatal stages. A small number of sacral crest-derived cells were found between
      the muscle layers and expressed the neuronal marker Hu. We conclude that sacral
      crest cells enter the hindgut by advancing on extrinsic fibers and, in
      aganglionic preparations, they form a small number of neurons at sites normally
      occupied by myenteric ganglia. We also examined the colons of ganglionated
      preparations and found sacral crest-derived cells associated with both extrinsic
      nerve fibers and nascent ganglia. Extrinsic nerve fibers serve as a route of
      entry for both rodent and avian sacral crest into the hindgut.

PMID- 21858822
TI  - Biophysical characterization and conformational stability of Ebola and Marburg
      virus-like particles.
AB  - The filoviruses, Ebola virus and Marburg virus, cause severe hemorrhagic fever
      with up to 90% human mortality. Virus-like particles of EBOV (eVLPs) and MARV
      (mVLPs) are attractive vaccine candidates. For the development of stable
      vaccines, the conformational stability of these two enveloped VLPs produced in
      insect cells was characterized by various spectroscopic techniques over a wide pH
      and temperature range. Temperature-induced aggregation of the VLPs at various pH
      values was monitored by light scattering. Temperature/pH empirical phase diagrams
      (EPDs) of the two VLPs were constructed to summarize the large volume of data
      generated. The EPDs show that both VLPs lose their conformational integrity above
      about 50 degrees C-60 degrees C, depending on solution pH. The VLPs were
      maximally thermal stable in solution at pH 7-8, with a significant reduction in
      stability at pH 5 and 6. They were much less stable in solution at pH 3-4 due to
      increased susceptibility of the VLPs to aggregation. The characterization data
      and conformational stability profiles from these studies provide a basis for
      selection of optimized solution conditions for further vaccine formulation and
      long-term stability studies of eVLPs and mVLPs.

PMID- 21858823
TI  - Subdivisions of the adult zebrafish subpallium by molecular marker analysis.
AB  - The morphology of the telencephalon displays great diversity among different
      vertebrate lineages. Particularly the everted telencephalon of ray-finned fishes
      shows a noticeably different morphology from the evaginated telencephalon of
      nonray-finned fishes and other vertebrates. This makes the comparison between the
      different parts of the telencephalon of ray-finned fishes and other vertebrates
      difficult. Based on neuroanatomical, neurochemical, and connectional data no
      consensus on the subdivisions of the adult telencephalon of ray-finned fishes and
      their relation to nuclei in the telencephalon of other vertebrates has been
      reached yet. For tetrapods, comparative expression pattern analysis of homologous
      developmental genes has been a successful approach to clarify homologies between
      different parts of the telencephalon. In the larval zebrafish, subdivisions of
      the subpallium have been proposed using conserved developmental gene expression.
      In this study, we investigate the subdivisions of the adult zebrafish
      telencephalon by analyzing the expression pattern of conserved molecular marker
      genes. We identify the boundary between the pallium and subpallium based on the
      complementary expression of dlx2a, dlx5a in the subpallium and tbr1, neurod in
      the pallium. Furthermore, combinatorial expression of Isl, nkx2.1b, lhx1b, tbr1,
      eomesa, emx1, emx2, and emx3 identifies striatal-like, pallidal-like, and septal
      like subdivisions within the subpallium. In contrast to previous models, we
      propose that the striatum and pallidum are stretched along the rostrocaudal axis
      of the telencephalon. Further, the septal nuclei derive from both the pallium and
      subpallium. On this basis, we present a new model for the subdivisions of the
      subpallium in teleost fish.

PMID- 21858824
TI  - Reliability evaluation of nonlinear design space in pharmaceutical product
      development.
AB  - Formulation design space of indomethacin tablets was investigated using a
      nonlinear response surface method incorporating multivariate spline interpolation
      (RSM-S). In this study, a resampling method with replacement was applied to
      evaluate the reliability of border on the design space estimated by RSM-S. The
      quantities of lactose, cornstarch, and microcrystalline cellulose were chosen as
      the formulation factors. Response surfaces were estimated using RSM-S, and the
      nonlinear design space was defined under the restriction of more than 3 kgf
      hardness and more than 70% dissolution 30 min before and after an accelerated
      test. The accuracy of the resampling method was elucidated and high correlation
      coefficients were produced. However, the distribution of the border on the design
      space generated by the resampling method was far from normal, and the confidence
      interval of the border was estimated using a nonparametric percentile technique.
      Consequently, the reliability of the design space was decreased by approaching
      the edge of the experimental design. RSM-S and this resampling method might be
      useful for estimating the reliability of nonlinear design space.

PMID- 21858825
TI  - Toxicological and toxicokinetic analysis of angiotensin (1-7) in two species.
AB  - The objectives of this study were to determine the potential systemic and local
      toxicity, as well as evaluate the toxicokinetic (TK) profile of angiotensin (1-7)
      [A(1-7)] when administered daily via subcutaneous injection for 28 days to
      Sprague-Dawley rats and Beagle dogs. A(1-7) is a member of the renin-angiotensin
      system and has undergone clinical evaluation for the treatment of chemotherapy
      induced myelosuppression. In this present study, A(1-7) was given at 10 mg/(kg
      day) for 28 days to rats and canines. At day 27, blood was harvested to evaluate
      the TK parameters. On day 28, systemic toxicology was evaluated. Following A(1-7)
      administration for 27 days, no plasma A(1-7) accumulation was detected in
      canines; however, increased A(1-7) plasma concentrations were detected in rats.
      Despite the accumulation observed in rats, no detectable toxicity was found
      following A(1-7) administration for 28 days. The TK analysis of A(1-7) revealed a
      plasma half-life of 20-30 min in both rats and canines. The time to maximum
      plasma concentration was found to be 15 and 26.25 min in rats and canines,
      respectively. This study shows that subcutaneous administration of A(1-7) at 10
      mg/(kg day) for 28 days did not lead to any detectable toxicities in either rats
      or canines.

PMID- 21858827
TI  - Donald L. Morton, MD ... a living legend in surgical oncology.

PMID- 21858828
TI  - Evidence-based treatment of early-stage melanoma.
AB  - The vast majority of patients with newly diagnosed melanoma are "early-stage" -
      ie, clinically localized to the primary cutaneous site. For such patients,
      surgery represents the mainstay of treatment; current standards of surgical
      management have evolved based on evidence obtained from randomized trials, large
      multi-center and single institutional databases, and consensus panels. Treatment
      strategies include wide excision of the primary site with margins dictated by
      important biological features such as Breslow tumor thickness, and sentinel node
      biopsy to surgically evaluate the regional nodal basins at risk. Sentinel node
      biopsy has become an important component of the initial management of many of
      these patients for accurate staging of regional lymph nodes, as well as enhanced
      regional disease control and improved survival in the patients with
      microscopically involved nodes. Evidence is presented that supports the rational
      use of these surgical strategies and reconciles some of the controversies that
      have emerged. The degree to which established national treatment guidelines are
      followed and the consequences of non-compliance with these guidelines have become
      the focus of recent clinical investigations; results of these efforts are also
      discussed.

PMID- 21858829
TI  - Ultrasound assessment of lymph nodes in the management of early-stage melanoma.
AB  - It has been suggested that ultrasound examination of regional lymph nodes
      provides staging and prognostic information that is as accurate as sentinel node
      biopsy in patients who present with cutaneous melanoma. However, in most studies
      the sensitivity of ultrasound in detecting nodal metastasis has been low (23% in
      a recent large series). For the present, sentinel node biopsy remains the most
      accurate method of regional node staging in patients with newly diagnosed
      melanoma.

PMID- 21858830
TI  - Role of selective sentinel lymph node dissection in head and neck melanoma.
AB  - Selective sentinel lymph node dissection (SLND) plays an important role in the
      staging of the regional nodal basins for head and neck (H&N) melanoma.
      Preoperative lymphoscintigraphy is mandatory to identify the regional nodal
      basin(s) accurately for a newly diagnosed H&N primary melanoma of at least 1mm or
      greater. A wide local excision should be delayed if SLN mapping is indicated, to
      minimize watershed effect and maximize accuracy in identifying the "true" SLN
      because of the complex lymphatic network in the H&N region. An experienced
      multidisciplinary team is required for optimal identification of H&N SLNs. In
      general, selective SLND can replace ELND to minimize the complications of a neck
      dissection. Completion lymph node dissection is only indicated when the SLN is
      positive. A nerve stimulator should be used during selective SLND in the parotid
      and posterior triangle to minimize the injury to the facial and spinal accessory
      nerve.

PMID- 21858832
TI  - Update on the melanoma staging system: the importance of sentinel node staging
      and primary tumor mitotic rate.
AB  - The 7(th) Edition of the AJCC Staging Manual includes a detailed summary of
      melanoma staging and prognosis. The revisions are summarized in this article,
      along with details on two key aspects of melanoma staging: the incorporation of
      mitotic rate of the primary melanoma and the key role of the sentinel lymph node
      biopsy (SLNB) in determining accurate staging for clinically occult nodal
      metastases. Primary tumor mitotic rate was introduced as a major criterion for
      melanoma staging and prognosis that replaces the Clark's level of invasion, and
      is now proven to be an important independent adverse predictor of survival.
      Analysis of the AJCC melanoma staging database demonstrated a significant inverse
      correlation between primary tumor mitotic rate (histologically defined as
      mitoses/mm(2) ) and survival. The use of SLNB reliably identifies melanoma
      patients with nodal micrometastases, enabling clinicians to identify patients
      with occult nodal metastases that would otherwise take months or years to become
      clinically palpable The number of nodal metastases was the most significant
      independent predictor of survival among all patients with stage III disease,
      including among patients with nodal micrometastases, and continues to be a
      primary criterion for defining Stage III melanoma. A clinical scoring system
      model and multivariate predictive tool under the auspices of the AJCC has led to
      a first-generation web-based predictive tool (www.melanomaprognosis.org).

PMID- 21858831
TI  - Clinically relevant information from sentinel lymph node biopsies of melanoma
      patients.
AB  - Careful laboratory evaluation of sentinel nodes (SNs) is critical to determine
      the presence of tumor. This requires evaluation of multiple full-face sections
      from the SN, using H&E staining and immunohistochemistry. In the future,
      molecular and genetic approaches may be adjunctive to microscopy. Number of tumor
      positive SNs and the amount and location of tumor in SNs correlate with tumor
      spread to non-sentinel nodes, subsequent recurrences and melanoma death,
      permitting patient assignment to a risk category.

PMID- 21858833
TI  - Neoadjuvant therapy for high-risk bulky regional melanoma.
AB  - Clinically detectable regional lymph node melanoma metastasis (AJCC stage IIIB-C)
      carries a risk of relapse and death that approaches 70% at 5 years. Surgical
      management is the cornerstone of therapy, with postoperative adjuvant therapy
      utilizing high-dose interferon alfa-2b (HDI). Neoadjuvant chemotherapy or
      immunotherapy in addition to surgery has been demonstrated to improve outcome in
      the management of patients with a variety of solid tumors. In patients with
      melanoma, the characteristics of the host immune response differ between patients
      with earlier stage and those with more advanced stages of disease (and
      particularly between those with measurable active disease and those without
      measurable gross disease) providing rationale for neoadjuvant approaches with
      immunotherapy. Host immune tolerance is now understood to impede the results of
      therapy for advanced disease, but appears to be less an issue for patients with
      microscopic high-risk operable disease, where the host may be more susceptible to
      immunologic interventions. Phase II studies have shown that neoadjuvant
      biochemotherapy has limited activity in melanoma patients with local-regional
      metastases, where chemotherapy may potentially alter the effects of
      immunotherapeutic agents. Studies of neoadjuvant HDI therapy for high-risk
      melanoma patients with bulky regional stage IIIB-C lymphadenopathy have shown
      unexpectedly high clinical and pathologic response rates, without increased
      morbidity. Through the design of neoadjuvant trials utilizing promising emerging
      melanoma therapeutics in which it is possible to obtain biopsy samples before and
      after therapy, a greater understanding of the dynamic interaction between tumors
      and the immune system is possible. This should lead to the identification of new
      targets for the treatment of melanoma and aid the development of new
      immunotherapy that may have greater specificity and less toxicity. This will
      simplify the evaluation of promising new combinations of agents with HDI to build
      on the clinical, immunologic, and molecular effect of this therapy for patients
      with melanoma.

PMID- 21858834
TI  - Local and intralesional therapy of in-transit melanoma metastases.
AB  - Regional relapse of melanoma may occur as satellite or in-transit metastases
      proximal to the primary tumor in the direction of the lymph flow. The management
      of in-transit metastases is challenging because the efficacy of treatment is
      largely dictated by the biological behavior of the patient's melanoma. This
      review examines local treatment modalities.

PMID- 21858835
TI  - Treatment of melanoma metastases in a limb by isolated limb perfusion and
      isolated limb infusion.
AB  - In-transit melanoma metastases are often confined to a limb. In this
      circumstance, treatment by isolated limb perfusion or isolated limb infusion can
      be a remarkably effective regional treatment option.

PMID- 21858836
TI  - Guidelines for lymphoscintigraphy and F18 FDG PET scans in melanoma.
AB  - Melanoma has a high potential to develop metastases. Accurate staging is
      essential for appropriate management. Sentinel node (SN) status is a powerful
      prognostic factor in early stage melanoma. Staging is assisted by SN biopsy after
      lymphoscintigraphy to locate all true SNs prior to biopsy. PET using F18-FDG can
      detect metastases and is used to restage patients with AJCC Stages III and IV
      disease before planning surgery with curative intent.

PMID- 21858837
TI  - Rationale for complete metastasectomy in patients with stage IV metastatic
      melanoma.
AB  - Patients with stage IV melanoma have usually been treated with systemic
      therapies; however, the overall survival for patients with this approach is
      disappointing. A complete surgical resection of metastatic disease to stage IV
      sites offers the best chance to maximize survival. This review article will
      present data supporting the position that if a complete metastasectomy is
      technically feasible, then surgery should be strongly considered the first option
      for properly selected patients with stage IV melanoma.

PMID- 21858838
TI  - Systemic treatment of metastatic melanoma: new approaches.
AB  - The field of melanoma therapeutics has experienced a dramatic paradigm shift over
      the last 12 months through recent discoveries of novel therapeutics targeting
      known oncogenes and immunotherapeutic antibodies. In this article, we review
      these findings and provide a framework to understand these discoveries, their
      significance in melanoma therapy, and role in clinical care. As this
      understanding grows, enduring therapeutic success may be achieved through
      tailored use of molecular markers and immunotherapies in sequential or
      combinatorial methods.

PMID- 21858839
TI  - Current and planned multicenter trials for patients with primary or metastatic
      melanoma.
AB  - Multicenter clinical trials have established new standards of care in the
      surgical and medical management of malignant melanoma. They have led to the
      testing of new therapies and improved outcomes for patients with loco-regional
      and distant disease. Many pressing questions remain, however, and additional
      multicenter trials are currently underway to address them. The purpose of this
      review is to summarize relevant ongoing and planned multicenter trials that have
      and continue to define current melanoma management.

PMID- 21858840
TI  - Community melanoma research: from start up to follow up.
AB  - Most surgical oncologists receive exposure to clinical studies in their
      fellowships; however they receive little if any practical knowledge as to how to
      become a clinical researcher. This article will provide a broad introduction to
      setting up a community based surgical oncology research program with emphasis on
      the practical issues necessary to be successful. Topics to be discussed include
      choosing appropriate studies, setting up the team, IRB issues, financial
      concerns, helpful hints for enrolling patients, and much more. Getting a program
      going can seem daunting but ultimately will be very rewarding for both the
      surgeon and their patients.

PMID- 21858841
TI  - Soil organic carbon and total nitrogen as affected by land use types in karst and
      non-karst areas of northwest Guangxi, China.
AB  - BACKGROUND: Human migration from the karst area to the non-karst area is an
      important approach for the restoration of degraded karst ecosystems. However, the
      effects of human-induced land-use change on soil properties are still unclear.
      The objective of this study was to investigate the effects of land use and parent
      material on soil organic carbon (SOC) and total nitrogen (TN) at a depth of 0-15
      cm in karst and non-karst areas in southwest China. RESULTS: In the karst area,
      SOC and TN under different land uses decreased significantly in the order of
      secondary forestland > scrubland and abandoned farmland > farmland, commercial
      forestland and forage grassland. In the non-karst area, SOC and TN were the
      highest in scrubland and grassland, and were significantly higher than those in
      farmland and commercial forestland. Because of differences in parent material,
      SOC and TN were significantly higher in the karst area than those in the non
      karst area. CONCLUSION: Abandoned farmland had the potential to increase SOC and
      TN significantly but land reclamation and cultivation had the opposite effect.
      SOC and TN were higher but cultivation-induced losses occurred more rapidly in
      calcareous soils than in red soils, indicating that more attention is needed for
      soil productivity and land use management in the karst area.

PMID- 21858842
TI  - Magnesium deficiency up-regulates Myod expression in rat skeletal muscle and
      C2C12 myogenic cells.
AB  - Magnesium (Mg) deficiency induces the production of free radicals, increases
      cytosolic ionized calcium concentration, and modulates the function of skeletal
      muscle in rats. The present study examined the effects of Mg deficiency on the
      gene expression of molecules related to myogenesis in the gastrocnemius muscle as
      well as in C2C12 myogenic cells. Ingestion of an Mg-deficient diet resulted in a
      lower weight of the gastrocnemius muscle and higher concentration of muscular
      TBARSs, an index of oxidative stress. Mg deficiency also enhanced the expression
      of Myod and myogenin. In vivo effects of Mg deficiency on myogenic gene
      expression were partially reproduced in in vitro C2C12 cells; expression of Myod
      was up-regulated by a mixed culture of myoblasts and myotubes with Mg-deficient
      medium, which related to the simultaneous up-regulation of Myhc IIb, a myotube
      specific protein. The culture with Mg-deficient medium did not increase the gene
      transcript level of HO-1, another marker of oxidative stress, suggesting that Mg
      deficiency-induced Myod expression does not result from oxidative stress.
      Furthermore, oxidative stress induced by hydrogen peroxide did not increase Myod
      expression, whereas the expression of Myod, myogenin and Myhc IIb was decreased
      by oxidative stress from the initial phase of differentiation. The effects of Mg
      deficiency depended on the stages of myogenesis; myoblast culture in Mg-deficient
      differentiation medium did not affect the expression of Myod and Myhc IIb. The
      present study revealed stage-dependent effects of Mg deficiency on myogenesis.

PMID- 21858843
TI  - Epinephrine-induced MMP expression is different between skeletal fibroblasts and
      myoblasts.
AB  - Skeletal fibroblasts and myoblasts are among the cell types currently being
      considered in cell therapy for ischaemic heart disease. To investigate whether
      the expression of the tissue-remodelling proteolytic enzymes matrix
      metalloproteinases (MMPs) and the cellular energy regulator AMP-activated protein
      kinase (AMPK) is comparable between the two cell lines in response to epinephrine
      treatment, mouse skeletal fibroblasts (NOR-10) and myoblasts (C2C12) were treated
      with or without a low (11 nmol.l(-1) ) or high (55 nmol.l(-1) ) dose of
      epinephrine for 2 or 6 h. Cellular MMP-3 expression was increased by the high
      dose epinephrine at both treatment periods in both cell lines. Cellular MMP-2 and
      MMP-13 expressions were amplified by the 2- or 6-h epinephrine incubation in
      fibroblasts. However, in myoblasts, such an increase was only seen at the longer
      treatment time. An elevated AMPKalpha expression was observed after a 2-h
      presence of epinephrine in both cell lines, which matches temporally with the
      early increased cellular MMP-2 and MMP-13 expression in fibroblasts. Activity of
      secreted MMP-2 increased only after 6-h epinephrine treatment in both cell types.
      Our data suggest that skeletal fibroblasts respond earlier to epinephrine
      application in terms of endogenous synthesis of the proteolytic and the energy
      homeostasis enzymes, whereas such response occurs later and to a milder dose of
      the beta adrenergic agonist in myoblasts.

PMID- 21858845
TI  - To go, or not to go, that is the question - six personal reflections on how
      geographic mobility may affect your career and life.

PMID- 21858844
TI  - Planctomycetes and eukaryotes: a case of analogy not homology.
AB  - Planctomycetes, Verrucomicrobia and Chlamydia are prokaryotic phyla, sometimes
      grouped together as the PVC superphylum of eubacteria. Some PVC species possess
      interesting attributes, in particular, internal membranes that superficially
      resemble eukaryotic endomembranes. Some biologists now claim that PVC bacteria
      are nucleus-bearing prokaryotes and are considered evolutionary intermediates in
      the transition from prokaryote to eukaryote. PVC prokaryotes do not possess a
      nucleus and are not intermediates in the prokaryote-to-eukaryote transition. Here
      we summarise the evidence that shows why all of the PVC traits that are currently
      cited as evidence for aspiring eukaryoticity are either analogous (the result of
      convergent evolution), not homologous, to eukaryotic traits; or else they are the
      result of horizontal gene transfers.

PMID- 21858846
TI  - Determinants of spontaneous surface antigen loss in hepatitis B e antigen
      negative patients with a low viral load.
AB  - Loss of hepatitis B surface antigen (HBsAg) usually indicates the cure of
      hepatitis B virus (HBV) infection. In spontaneous hepatitis B e antigen (HBeAg)
      seroconverters, lower serum HBsAg and HBV DNA levels have been shown to be
      associated with HBsAg loss over time. However, little is known about their
      impacts on HBsAg loss in HBeAg-negative patients with limited viral replication.
      A total of 688 HBeAg-negative patients with baseline serum HBV DNA levels <2000
      IU/mL were enrolled in Taiwan. The relationships of HBsAg and HBV DNA levels with
      subsequent HBsAg loss were investigated. In a mean follow-up of 11.6 years, the
      average annual rate of HBsAg loss was 1.6%. Baseline HBsAg and HBV DNA levels
      were inversely associated with subsequent HBsAg loss. When compared to patients
      who had HBsAg levels >1000 IU/mL, the rates of HBsAg loss were significantly
      higher in patients with HBsAg levels of 100-999, 10-99, and <10 IU/mL, with
      hazard ratios of 2.5 (95% confidence interval [CI], 1.6-4.0), 2.8 (95% CI, 1.6
      5.0), and 13.2 (95% CI, 8.1-21.5), respectively. Multivariate analysis showed
      that HBsAg level, but not HBV DNA, remained as an independent factor. The
      adjusted hazard ratio of HBsAg loss was 13.2 (95% CI, 7.8-22.1) for HBsAg level
      <10 versus >= 1000 IU/mL. When compared to HBV DNA level by receiver operating
      characteristic curve analysis, HBsAg level served as a better predictor of both 5
      year and 10-year HBsAg loss. CONCLUSION: In HBeAg-negative patients with HBV
      genotype B or C infection who have HBV DNA level <2000 IU/mL, HBsAg level <10
      IU/mL is the strongest predictor of HBsAg loss.

PMID- 21858847
TI  - Burden of cirrhosis on older Americans and their families: analysis of the health
      and retirement study.
AB  - Prevalence of cirrhosis among older adults is expected to increase; therefore, we
      studied the health status, functional disability, and need for supportive care in
      a large national sample of individuals with cirrhosis. A prospective cohort of
      individuals with cirrhosis was identified within the longitudinal, nationally
      representative Health and Retirement Study. Cirrhosis cases were identified in
      linked Medicare data via ICD-9-CM (International Classification of Diseases,
      Ninth Revision, Clinical Modification) codes and compared to an age-matched
      cohort without cirrhosis. Two primary outcome domains were assessed: (1)
      patients' health status (perceived health status, comorbidities, health care
      utilization, and functional disability as determined by activities of daily
      living and instrumental activities of daily living), and (2) informal caregiving
      (hours of caregiving provided by a primary informal caregiver and associated
      cost). Adjusted negative binomial regression was used to assess the association
      between cirrhosis and functional disability. A total of 317 individuals with
      cirrhosis and 951 age-matched comparators were identified. Relative to the
      comparison group, individuals with cirrhosis had worse self-reported health
      status, more comorbidities, and used significantly more health care services
      (hospitalizations, nursing home stays, physician visits; P < 0.001 for all
      bivariable comparisons). They also had greater functional disability (P < 0.001
      for activities of daily living and instrumental activities of daily living),
      despite adjustment for covariates such as comorbidities and health care
      utilization. Individuals with cirrhosis received more than twice the number of
      informal caregiving hours per week (P < 0.001), at an annual cost of US $4700 per
      person. CONCLUSION: Older Americans with cirrhosis have high rates of disability,
      health care utilization, and need for informal caregiving. Improved care
      coordination and caregiver support is necessary to optimize management of this
      frail population.

PMID- 21858848
TI  - Unusual extrahepatic metastasis to the soft tissue of the left cervical neck area
      from hepatic epithelioid hemangioendothelioma.

PMID- 21858849
TI  - Higher serum testosterone is associated with increased risk of advanced hepatitis
      C-related liver disease in males.
AB  - Males have strikingly increased risk of advanced liver disease. However, the
      association between testosterone and risk of hepatitis C virus (HCV)-related
      advanced liver disease is unknown. We performed a cross-sectional study in male
      veterans with chronic HCV. Blood samples were obtained to measure total serum
      testosterone and perform the FibroSURE-ActiTest. Other risk-factor data were
      obtained through systematic questionnaires (e.g., alcohol), physical measurements
      (e.g., body mass index), and serological tests (e.g., viral load). The
      association between total testosterone and risk of advanced hepatic fibrosis (F3
      and F3/F4) and inflammatory activity (A3 and A2/3) measured by the FibroSURE
      ActiTest was evaluated with logistic regression. A total of 308 eligible study
      participants were prospectively recruited (mean age: 57; 52% African-American).
      There were 105 cases with advanced fibrosis and 203 mild fibrosis controls as
      well as 88 cases with advanced inflammatory activity and 220 mild activity
      controls. Mean total serum testosterone was significantly higher in advanced
      fibrosis cases as well as advanced inflammatory activity cases, compared to mild
      disease controls (6.0 versus 5.3 ng/mL and 5.9 versus 5.4 ng/mL, respectively).
      We observed a significant 25% increase in advanced fibrosis risk and 15% increase
      in advanced inflammatory activity risk for each 1-ng/mL increase in total serum
      testosterone. Total testosterone in the upper tertile was associated with an even
      greater excess risk of advanced fibrosis than advanced inflammatory activity
      (odds ratio [OR](adjusted advanced fibrosis) = 3.74; 95% CI: 1.86-6.54 versus
      OR(adjusted advanced inflammatory activity) = 2.23; 95% CI: 1.07-4.93,
      respectively). CONCLUSIONS: Total serum testosterone is associated with an
      increased risk of both advanced hepatic fibrosis and advanced hepatic
      inflammatory activity in HCV-infected men. Testosterone may be important in the
      pathogenesis of HCV-related advanced liver disease in males.

PMID- 21858851
TI  - Multi-level modeling of aspects associated with poor mental health in a sample of
      prehospital emergency professionals.
AB  - BACKGROUND: The goal of this paper is to investigate the respective influence of
      work characteristics, the effort-reward ratio, and overcommitment on the poor
      mental health of out-of-hospital care providers. METHODS: 333 out-of-hospital
      care providers answered a questionnaire that included queries on mental health
      (GHQ-12), demographics, health-related information and work characteristics,
      questions from the Effort-Reward Imbalance Questionnaire, and items about
      overcommitment. A two-level multiple regression was performed between mental
      health (the dependent variable) and the effort-reward ratio, the overcommitment
      score, weekly number of interventions, percentage of non-prehospital transport of
      patients out of total missions, gender, and age. Participants were first-level
      units, and ambulance services were second-level units. We also shadowed ambulance
      personnel for a total of 416 hr. RESULTS: With cutoff points of 2/3 and 3/4
      positive answers on the GHQ-12, the percentages of potential cases with poor
      mental health were 20% and 15%, respectively. The effort-reward ratio was
      associated with poor mental health (P < 0.001), irrespective of age or gender.
      Overcommitment was associated with poor mental health; this association was
      stronger in women (beta = 0.054) than in men (beta = 0.020). The percentage of
      prehospital missions out of total missions was only associated with poor mental
      health at the individual level. CONCLUSIONS: Emergency medical services should
      pay attention to the way employees perceive their efforts and the rewarding
      aspects of their work: an imbalance of those aspects is associated with poor
      mental health. Low perceived esteem appeared particularly associated with poor
      mental health. This suggests that supervisors of emergency medical services
      should enhance the value of their employees' work. Employees with overcommitment
      should also receive appropriate consideration. Preventive measures should target
      individual perceptions of effort and reward in order to improve mental health in
      prehospital care providers.

PMID- 21858850
TI  - Effects of hypolipidemic agent nordihydroguaiaretic acid on lipid droplets and
      hepatitis C virus.
AB  - Hepatitis C virus (HCV) relies on host lipid metabolic pathways for its
      replication, assembly, secretion, and entry. HCV induces de novo lipogenesis,
      inhibits beta-oxidation, and lipoprotein export resulting in a lipid-enriched
      cellular environment critical for its proliferation. We investigated the effects
      of a hypolipidemic agent, nordihydroguaiaretic acid (NDGA), on host lipid/fatty
      acid synthesis and HCV life cycle. NDGA negated the HCV-induced alteration of
      host lipid homeostasis. NDGA decreased sterol regulatory element binding protein
      (SREBP) activation and enhanced expression of genes involved in beta-oxidation.
      NDGA inhibited very low-density lipoprotein (VLDL) secretion by affecting
      mediators of VLDL biosynthesis. Lipid droplets (LDs), the neutral lipid storage
      organelles, play a key role in HCV morphogenesis. HCV induces accumulation and
      perinuclear distribution of LDs, whereas NDGA most notably reduced the overall
      number and increased the average size of LDs. The antiviral effects of NDGA
      resulted in reduced HCV replication and secretion. CONCLUSION: NDGA-mediated
      alterations of host lipid metabolism, LD morphology, and VLDL transport appear to
      negatively influence HCV proliferation.

PMID- 21858852
TI  - Comparing the risk factors associated with serious versus and less serious work
      related injuries in Ontario between 1991 and 2006.
AB  - BACKGROUND: The objective of this study was to examine and compare the
      demographic and labor market risks for more serious and less serious work-related
      injuries and illnesses. METHODS: Secondary analysis of accepted workers'
      compensation claims in Ontario, combined with labor force estimates for the
      period 1991 to 2006. Serious injuries and illnesses were claims resulting in wage
      replacement. Less serious injuries and illnesses were claims only requiring
      health care. Regression models examined the relationship between demographic and
      labor market characteristics (age, gender, industry, job tenure, and
      unemployment) and claim type. RESULTS: Relative risk estimates for serious and
      less serious claims were not concordant across age, gender and industry
      employment groups. For example, while the mining and utilities and the
      construction industry had an increased probability of reporting NLTCs, they had a
      decreased probability of reporting LTCs. CONCLUSIONS: The risk for serious and
      less serious work-related injury and illness claims differ by demographic and
      labor market groups. The use of composite measures that combine wage-replacement
      and health care only claims should be considered when using compensation data for
      surveillance and primary prevention targeting strategies.

PMID- 21858853
TI  - Re: Joint modeling of missing data due to non-participation and death in
      longitudinal aging studies by K. B. Rajan and S. E. Leurgans, Statistics in
      Medicine 2010; 29:2260-2268.

PMID- 21858855
TI  - Toxicity and uptake of TRI- and dibutyltin in Daphnia magna in the absence and
      presence of nano-charcoal.
AB  - Butyltins (BTs), such as tributyltin (TBT) and dibutyltin (DBT), are toxic to
      aquatic organisms, but the presence of the strong adsorbent, black carbon (BC),
      can markedly influence BT toxicity and uptake in organisms. In the present study,
      the acute toxicity and uptake of TBT and DBT in the crustacean, Daphnia magna,
      were investigated with and without addition of nano-charcoal at different pHs and
      water hardnesses. The results showed that the toxicity of TBT and DBT increased
      by lowering the pH from 8 to 6. This reflects a relatively higher toxicity of
      cationic BT species than of the neutral species. At pH 6, by enhancing the water
      hardness of the media from 0.6 to 2.5 mM, the toxicity of TBT and DBT
      consistently decreased due to competitive binding of bivalent cations (Mg2+,
      Ca2+) to biotic ligands of D. magna. Furthermore, the toxicity of TBT to D. magna
      significantly decreased in the presence of nano-charcoal compared with
      experiments without nano-charcoal at pH 6 and 8, while no significant decrease in
      toxicity of DBT was observed in the presence of nano-charcoal. This can be
      attributed to the insignificant decrease of free DBT concentration in the
      presence of nano-charcoal compared with that for TBT. Conversely, it was observed
      that more TBT and DBT were taken up in D. magna in the presence of nano-charcoal
      due to the uptake of TBT or DBT associated with nano-charcoal by Daphnia in gut
      systems, as seen by light microscopy. This indicated that only free nonadsorbed
      BTs were toxic to D. magna, at least during short periods of exposure.

PMID- 21858857
TI  - Suture anchor versus screw fixation for greater tuberosity fractures of the
      humerus--a biomechanical study.
AB  - Suture anchors and screws are commonly used for fixation of humeral greater
      tuberosity (GT) fractures in either arthroscopic or open surgeries, but no
      biomechanical studies have been performed to compare the strength of fixation
      constructs using these two implants. This cadaveric study aimed to compare the
      biomechanical strength of three different fixation constructs in the management
      of GT fractures: Double-Row Suture Anchor Fixation (DR); Suture-Bridge Technique
      using suture anchors and knotless suture anchors (SB); and Two-Screw Fixation
      (TS). The experimental procedure was designed to assess fracture displacement
      after cyclic loading, failure load, and failure mode of the fixation construct.
      Significant differences were found among the SB (321 N), DR (263 N), and TS (187
      N) groups (SB > DR > TS, p < 0.05) in the mean force of cyclic loading to create
      3 mm displacement. Regarding the mean force of cyclic loading to create 5 mm
      displacement and ultimate failure load, no significant difference was found
      between the DR (370 N, 480 N) and SB (399 N, 493 N) groups, but both groups
      achieved superior results compared with the TS group (249 N, 340 N) (p < 0.05).
      The results suggested that the suture anchor constructs would be stronger than
      the fixation construct using screws for the humeral GT fracture.

PMID- 21858856
TI  - Effect of implantation site and injury condition on host response to human
      derived fascia lata ECM in a rat model.
AB  - The host response and remodeling of ECM scaffolds are believed to be critical
      determinants of success or failure in repair or reconstructive procedures. Host
      response has been investigated in subcutaneous or abdominal wall implantation
      models. The extent to which evaluation of the host response to ECM intended for
      tendon or ligament repair should be performed in an orthotopic site is not known.
      This study compared the host response to human-derived fascia lata ECM among
      various implantation sites in the rat model. Results showed that a xenograft in
      the rat shoulder does not exhibit a different host response at 7 days from
      xenograft in the body wall, suggesting that either site may be appropriate to
      study the early host response to biologic grafts as well as the effect of various
      treatments aimed to modify the early host response. By 28 days, a xenograft in
      the rat shoulder does elicit a unique host response from that seen in the body
      wall. Therefore, it may be more appropriate to use an orthotopic shoulder model
      for investigating the long-term host response and remodeling of biologic grafts
      to be used for rotator cuff repair.

PMID- 21858858
TI  - Compensation of slice profile mismatch in combined spin- and gradient-echo echo
      planar imaging pulse sequences.
AB  - Combined acquisition of gradient-echo and spin-echo signals in MRI time series
      reveals additional information for perfusion-weighted imaging and functional MRI
      because of differences in the sensitivity of gradient-echo and spin-echo
      measurements to the properties of the underlying vascular architecture. The
      acquisition of multiple echo trains within one time frame facilitates the
      simultaneous estimation of the transversal relaxation parameters R2 and R2*.
      However, the simultaneous estimation of these parameters tends to be incorrect in
      the presence of slice profile mismatches between signal excitation and subsequent
      refocusing pulses. It is shown here that improvements in pulse design reduced R2
      and R2* estimation errors. Further improvements were achieved by augmented
      parameter estimation through the introduction of an additional parameter delta to
      correct for discordances in slice profiles to facilitate more quantitative
      measurements. Moreover, the analysis of time-resolved acquisitions revealed that
      the temporal stability of R2 estimates could be increased with improved pulse
      design, counteracting low contrast-to-noise ratios in spin-echo-based perfusion
      and functional MRI.

PMID- 21858859
TI  - Accuracy of the cylinder approximation for susceptometric measurement of
      intravascular oxygen saturation.
AB  - Susceptometry-based MR oximetry has previously been shown suitable for
      quantifying hemoglobin oxygen saturation in large vessels for studying vascular
      reactivity and quantification of global cerebral metabolic rate of oxygen
      utilization. A key assumption underlying this method is that large vessels can be
      modeled as long paramagnetic cylinders. However, bifurcations, tapering,
      noncircular cross-section, and curvature of these vessels produce substantial
      deviations from cylindrical geometry, which may lead to errors in hemoglobin
      oxygen saturation quantification. Here, the accuracy of the "long cylinder"
      approximation is evaluated via numerical computation of the induced magnetic
      field from 3D segmented renditions of three veins of interest (superior sagittal
      sinus, femoral and jugular vein). At a typical venous oxygen saturation of 65%,
      the absolute error in hemoglobin oxygen saturation estimated via a closed-form
      cylinder approximation was 2.6% hemoglobin oxygen saturation averaged over three
      locations in the three veins studied and did not exceed 5% for vessel tilt angles
      <30 degrees  at any one location. In conclusion, the simulation results provide a
      significant level of confidence for the validity of the cylinder approximation
      underlying MR susceptometry-based oximetry of large vessels.

PMID- 21858860
TI  - Three-dimensional MRI with independent slab excitation and encoding.
AB  - Three-dimensional MRI is typically performed with the same orientation for
      radiofrequency slab excitation and slab select phase encoding. We introduce
      independent slab excitation and encoding to create a new degree of freedom in
      three-dimensional MRI, which is the angular relationship between the prescribed
      excitation volume and the voxel encoding grid. By separating the directions of
      slab excitation and slab phase encoding, the independent slab excitation and
      encoding method allows choice of optimal voxel orientation, while maintaining
      volume excitation based on anatomic landmarks. The method requires simple pulse
      sequence modifications and uses standard image reconstruction followed by removal
      of aliasing and image reformatting. The independent slab excitation and encoding
      method enables arbitrary oblique angle imaging using fixed voxel encoding
      gradients to maintain similar eddy current, concomitant field, or magnetic dipole
      effects independent of the oblique angle of excitation. We apply independent slab
      excitation and encoding to phase and susceptibility-weighted imaging using fixed
      voxel encoding aligned with the main magnetic field to demonstrate its value in
      both standardizing and improving image contrast, when using arbitrary oblique
      imaging volumes.

PMID- 21858861
TI  - Fast diffusion-weighted steady state free precession imaging of in vivo knee
      cartilage.
AB  - Quantification of molecular diffusion with steady state free precession (SSFP) is
      complicated by the fact that diffusion effects accumulate over several repetition
      times (TR) leading to complex signal dependencies on transverse and longitudinal
      magnetization paths. This issue is commonly addressed by setting TR > T(2),
      yielding strong attenuation of all higher modes, except of the shortest ones. As
      a result, signal attenuation from diffusion becomes T(2) independent but signal
      to-noise ratio (SNR) and sequence efficiency are remarkably poor. In this work,
      we present a new approach for fast in vivo steady state free precession diffusion
      weighted imaging of cartilage with TR << T(2) offering a considerable increase in
      signal-to-noise ratio and sequence efficiency. At a first glance, prominent
      coupling between magnetization paths seems to complicate quantification issues in
      this limit, however, it is observed that diffusion effects become rather T(2)
      (DeltaD ~ 1/10 DeltaT(2)) but not T(1) independent (DeltaD ~ 1/2 DeltaT(1)) for
      low flip angles alpha ~ 10 - 15 degrees . As a result, fast high-resolution (0.35
      * 0.35 - 0.50 * 0.50 mm(2) in-plane resolution) quantitative diffusion-weighted
      imaging of human articular cartilage is demonstrated at 3.0 T in a clinical setup
      using estimated T(1) and T(2) or a combination of measured T(1) and estimated
      T(2) values.

PMID- 21858862
TI  - A quantitative pressure and microbubble-size dependence study of focused
      ultrasound-induced blood-brain barrier opening reversibility in vivo using MRI.
AB  - Focused ultrasound in conjunction with the systemic administration of
      microbubbles has been shown to open the blood-brain barrier (BBB) selectively,
      noninvasively and reversibly. In this study, we investigate the dependence of the
      BBB opening's reversibility on the peak-rarefactional pressure (0.30-0.60 MPa) as
      well as the microbubble size (diameters of 1-2, 4-5, or 6-8 MUm) in mice using
      contrast-enhanced T(1)-weighted (CE-T(1)) MR images (9.4 T). Volumetric
      measurements of the diffusion of Gd-DTPA-BMA into the brain parenchyma were used
      for the quantification of the BBB-opened region on the day of sonication and up
      to 5 days thereafter. The volume of opening was found to increase with both
      pressure and microbubble diameter. The duration required for closing was found to
      be proportional to the volume of opening on the day of opening, and ranged from
      24 h, for the smaller microbubbles, to 5 days at high peak-rarefactional
      pressures. Overall, larger bubbles did not show significant differences. Also,
      the extent of BBB opening decreased radially towards the focal region until the
      BBB's integrity was restored. In the cases where histological damage was
      detected, it was found to be highly correlated with hyperintensity on the
      precontrast T(1) images.

PMID- 21858864
TI  - Understanding quantitative pulsed CEST in the presence of MT.
AB  - Phantom experiments in agar and ammonium chloride were performed to evaluate a
      three-pool model of magnetization transfer and chemical exchange saturation
      transfer (CEST) in a pulsed saturation transfer experiment. The utility of the
      pulsed CEST method was demonstrated by varying the pH of the phantoms and
      observing the effect upon the CEST spectra both with and without the solid agar
      (the magnetization transfer pool), while fitting the spectra to the Bloch
      equation model with exchange. Pulsed CEST could be used to robustly quantify
      parameters related to CEST, including the exchange rate constant describing
      proton exchange with free water and the concentration of exchanging protons.
      Furthermore, the exchange rate constant and the CEST pool offset frequency of the
      ammonium chloride remained unchanged in the presence of a magnetization transfer
      pool. The logarithm of the fitted exchange rate constant was linearly related to
      pH: this relationship was maintained in the presence of magnetization transfer.

PMID- 21858863
TI  - Parallel traveling-wave MRI: a feasibility study.
AB  - Traveling-wave magnetic resonance imaging utilizes far fields of a single-piece
      patch antenna in the magnet bore to generate radio frequency fields for imaging
      large-size samples, such as the human body. In this work, the feasibility of
      applying the "traveling-wave" technique to parallel imaging is studied using
      microstrip patch antenna arrays with both the numerical analysis and experimental
      tests. A specific patch array model is built and each array element is a
      microstrip patch antenna. Bench tests show that decoupling between two adjacent
      elements is better than -26-dB while matching of each element reaches -36-dB,
      demonstrating excellent isolation performance and impedance match capability. The
      sensitivity patterns are simulated and g-factors are calculated for both unloaded
      and loaded cases. The results on B 1- sensitivity patterns and g-factors
      demonstrate the feasibility of the traveling-wave parallel imaging. Simulations
      also suggest that different array configuration such as patch shape, position and
      orientation leads to different sensitivity patterns and g-factor maps, which
      provides a way to manipulate B(1) fields and improve the parallel imaging
      performance. The proposed method is also validated by using 7T MR imaging
      experiments.

PMID- 21858865
TI  - Virtual dye angiography: flow visualization for MRI-guided interventions.
AB  - In magnetic resonance imaging-guided cardiovascular interventional procedures, it
      is valuable to be able to visualize blood flow immediately and interactively in
      selected regions. In particular, it is useful to assess normal or pathological
      communications between specific heart chambers and vessels. Phase-contrast
      velocity mapping is not suitable for this purpose as it requires too much data
      and is not capable of determining directly if blood originating in one location
      travels to a nearby location. This article presents a novel flow visualization
      method called virtual dye angiography that enables visualization of blood flow
      analogous to selective catheter angiography. The method uses two-dimensional
      radio frequency pulses to achieve interactive, intermittent, targeted saturation
      of a localized region of the blood pool. The flow of the saturated spins is
      observed directly on real-time images or, in an enhanced manner, using ECG
      synchronized background subtraction. The modular nature of the technique allows
      for easy and seamless integration into a real-time, interactive imaging system
      with minimal overhead. We present initial results in animals and in a healthy
      human volunteer.

PMID- 21858866
TI  - Parallel magnetic resonance imaging using localized receive arrays with sinc
      interpolation (PILARS).
AB  - Large arrays with localized coil sensitivity make it possible to use parallel
      imaging to significantly accelerate MR imaging speed. However, the need for auto
      calibration signals limits the actual acceleration factors achievable with large
      arrays. This paper presents a novel method for parallel imaging with large
      arrays. The method uses Sinc kernels for k-space data interpolation that only
      requires one phase parameter to be estimated using a small size of calibration
      signals. Simulations based on synthetic array data and phantom experiments show
      that the new method can achieve higher actual acceleration factors with
      comparable reconstruction quality.

PMID- 21858867
TI  - Time-interleaved acquisition of modes: an analysis of SAR and image contrast
      implications.
AB  - As the magnetic field strength and therefore the operational frequency in MRI are
      increased, the radiofrequency wavelength approaches the size of the human
      head/body, resulting in wave effects which cause signal decreases and dropouts.
      Especially, whole-body imaging at 7 T and higher is therefore challenging.
      Recently, an acquisition scheme called time-interleaved acquisition of modes has
      been proposed to tackle the inhomogeneity problems in high-field MRI. The basic
      premise is to excite two (or more) different B 1+ modes using static
      radiofrequency shimming in an interleaved acquisition, where the complementary
      radiofrequency patterns of the two modes can be exploited to improve overall
      signal homogeneity. In this work, the impact of time-interleaved acquisition of
      mode on image contrast as well as on time-averaged specific absorption rate is
      addressed in detail. Time-interleaved acquisition of mode is superior in B 1+
      homogeneity compared with conventional radiofrequency shimming while being highly
      specific absorption rate efficient. Time-interleaved acquisition of modes can
      enable almost homogeneous high-field imaging throughout the entire field of view
      in PD, T(2) , and T(2) *-weighted imaging and, if a specified homogeneity
      criterion is met, in T(1) -weighted imaging as well.

PMID- 21858868
TI  - Blipped-controlled aliasing in parallel imaging for simultaneous multislice echo
      planar imaging with reduced g-factor penalty.
AB  - Simultaneous multislice Echo Planar Imaging (EPI) acquisition using parallel
      imaging can decrease the acquisition time for diffusion imaging and allow full
      brain, high-resolution functional MRI (fMRI) acquisitions at a reduced repetition
      time (TR). However, the unaliasing of simultaneously acquired, closely spaced
      slices can be difficult, leading to a high g-factor penalty. We introduce a
      method to create interslice image shifts in the phase encoding direction to
      increase the distance between aliasing pixels. The shift between the slices is
      induced using sign- and amplitude-modulated slice-select gradient blips
      simultaneous with the EPI phase encoding blips. This achieves the desired shifts
      but avoids an undesired "tilted voxel" blurring artifact associated with previous
      methods. We validate the method in 3* slice-accelerated spin-echo and gradient
      echo EPI at 3 T and 7 T using 32-channel radio frequency (RF) coil brain arrays.
      The Monte-Carlo simulated average g-factor penalty of the 3-fold slice
      accelerated acquisition with interslice shifts is <1% at 3 T (compared with 32%
      without slice shift). Combining 3* slice acceleration with 2* inplane
      acceleration, the g-factor penalty becomes 19% at 3 T and 10% at 7 T (compared
      with 41% and 23% without slice shift). We demonstrate the potential of the method
      for accelerating diffusion imaging by comparing the fiber orientation
      uncertainty, where the 3-fold faster acquisition showed no noticeable
      degradation.

PMID- 21858869
TI  - Improved initial value estimation for short echo time magnetic resonance
      spectroscopy spectral analysis using short T2 signal attenuation.
AB  - Robust spectral analysis of magnetic resonance spectroscopy data frequently uses
      a spectral model with prior metabolite signal information within a nonlinear
      least squares optimization algorithm. Starting values for the spectral model
      greatly influence the final results. Short echo time magnetic resonance
      spectroscopy contains broad signals that overlap with metabolite signals,
      complicating the estimation of starting values. We describe a method for more
      robust initial value estimation using a filter to attenuate short T(2) signal
      contributions (e.g., macromolecules or residual lipids). The method attenuates
      signals by truncating early points in the data set. Metabolite peak estimation is
      simplified by the removal of broad, short T(2) signals, and corrections for
      metabolite signal truncation are described. Short echo time simulated Monte Carlo
      data and in vivo data were used to validate the method. Areas for metabolite
      signals in the Monte Carlo data with singlet (N-acetylaspartate, creatine,
      choline) and singlet-like (myo-inositol) resonances were estimated within 10% of
      actual value for various metabolite line widths, signal-to-noise ratios, and
      underlying broad signal contributions. Initial value estimates of in vivo
      magnetic resonance spectroscopy data were within 14% of metabolite area ratios
      relative to the creatine peak fitted using established magnetic resonance
      spectroscopy spectral analysis software.

PMID- 21858871
TI  - Care at the end of life for people with dementia living in a care home: a
      qualitative study of staff experience and attitudes.
AB  - OBJECTIVE: The aim of this study is to examine barriers and facilitators to care
      home staff delivering improved end-of-life care for people with dementia. METHOD:
      Individual qualitative interviews of 58 staff in a 120-bed nursing home where the
      staff and the residents' religion differed were carried out. Interviews continued
      until a maximum variation sample was achieved and theoretical saturation was
      reached. RESULTS: The staff felt warmly towards the residents and felt they could
      recognise when they were near death. Care staff, nurses and doctors did not see
      themselves as a team and communicated poorly with relatives about approaching
      death. The staff used opaque euphemisms and worried about being blamed. They were
      often unaware of or had concerns about the validity of advance care plans. They
      knew of the religious rituals around death but frequently misunderstood religious
      tradition. CONCLUSION: The staff require education and support about discussing
      and implementing plans around care at the end of life in dementia and about
      cultural issues around death to improve practice. This would enable the staff to
      implement advance care plans, knowing that they will be supported. Education
      would encompass communicating the complicated, unpredictable path of dementia
      near the time of death explicitly but sensitively, including recognising that
      people often do not hear difficult messages and are unable to take on large
      quantities of information at once. The staff need to know about the resident's
      religious and cultural ideas as well as ritual practice.

PMID- 21858870
TI  - A two-stage approach for measuring vascular water exchange and arterial transit
      time by diffusion-weighted perfusion MRI.
AB  - Changes in the exchange rate of water across the blood-brain barrier, denoted
      k(w), may indicate blood-brain barrier dysfunction before the leakage of large
      molecule contrast agents is observable. A previously proposed approach for
      measuring k(w) is to use diffusion-weighted arterial spin labeling to measure the
      vascular and tissue fractions of labeled water, because the vascular-to-tissue
      ratio is related to k(w). However, the accuracy of diffusion-weighted arterial
      spin labeling is affected by arterial blood contributions and the arterial
      transit time (tau(a)). To address these issues, a two-stage method is proposed
      that uses combinations of diffusion-weighted gradient strengths and post-labeling
      delays to measure both tau(a) and k(w). The feasibility of this method was
      assessed by acquiring diffusion-weighted arterial spin labeling data from seven
      healthy volunteers. Repeat measurements and Monte Carlo simulations were
      conducted to determine the precision and accuracy of the k(w) estimates. Average
      grey and white matter k(w) values were 110 +/- 18 and 126 +/- 18 min(-1),
      respectively, which compare favorably to blood-brain barrier permeability
      measurements obtained with positron emission tomography. The intrasubject
      coefficient of variation was 26% +/- 23% in grey matter and 21% +/- 17% in white
      matter, indicating that reproducible k(w) measurements can be obtained.

PMID- 21858873
TI  - Effects of perinatal asphyxia on rat striatal cytoskeleton.
AB  - Perinatal asphyxia (PA) is a medical condition associated with a high short-term
      morbimortality and different long-term neurological diseases. In previous works,
      we have shown that neuronal and synaptic changes in rat striatum lead to ubi
      protein accumulation in post-synaptic density (PSD) after six months of sub
      severe PA. However, very little is known about the synaptic and related
      structural modifications induced by PA in young rats. In the present work, we
      studied neuronal cytoskeleton modifications in striatum induced by subsevere PA
      in 30-day-old rats. We observed a significant decrease in the number of neurons,
      in particular calbindin immunoreactive neurons after PA. In addition, it was also
      observed that actin cytoskeleton was highly modified in the PSD as well as an
      increment of F-actin staining by Phalloidin-alexa(488) in the striatum of PA
      rats. Using correlative fluorescence-electron microscopy photooxidation, we
      confirmed and extended confocal observations. F-actin staining augmentation was
      mostly related with an increment in the number of mushroom-shaped spines.
      Consistent with microscopic data, Western blot analysis revealed a beta-actin
      increment in PSD in PA rats. On the other hand, MAP-2 immunostaining was
      decreased after PA, being NF-200 expression unmodified. Although neuronal death
      was observed, signs of generalized neurodegeneration were absent. Taken together
      these results showed early post-synaptic F-actin cytoskeleton changes induced by
      PA with slightly modifications in the other components of the neuronal
      cytoskeleton, suggesting that F-actin accumulation in the dendritic spines could
      be involved in the neuronal loss induced by PA.

PMID- 21858874
TI  - Proteomic identification of novel targets regulated by the mammalian target of
      rapamycin pathway during oligodendrocyte differentiation.
AB  - Previous work from our laboratory demonstrated that the mammalian target of
      rapamycin (mTOR) is active during and required for oligodendrocyte progenitor
      cell (OPC) differentiation. Here, we applied an iTRAQ mass spectrometry-based
      proteomic approach to identify novel targets of the mTOR pathway during OPC
      differentiation. Among the 978 proteins identified in this study, 328 (34%)
      exhibited a greater than 20% change (P < 0.05) in control versus rapamycin
      treated cultures following 4 days of differentiation in vitro. Interestingly, 197
      (20%) proteins were elevated in rapamycin-treated cultures, while 131 (13%)
      proteins were downregulated by rapamycin. In support of our previous data,
      inhibiting mTOR caused a dramatic reduction in the expression of myelin proteins.
      mTOR also was required for the induction of proteins involved in cholesterol and
      fatty acid synthesis, as well as the expression of many cytoskeletal proteins,
      cell signaling components, and nuclear/transcriptional regulators. Of particular
      interest was the identification of several critical mediators of oligodendrocyte
      differentiation. Specifically, mTOR activity controls the developmentally
      programmed upregulation of the prodifferentiation factors Fyn and Quaking,
      whereas the expression of the differentiation repressor Gpr17 was elevated by
      mTOR inhibition. These data reveal a distinct signature of mTOR-regulated protein
      expression during OPC differentiation.

PMID- 21858875
TI  - A Boyden chamber-based method for characterization of astrocyte protrusion
      localized RNA and protein.
AB  - The Boyden chamber assay has been developed for various cell migration and
      invasion protocols. One variant of the Boyden chamber assay is the pseudopodium
      isolation assay, which has been developed to identify RNA and proteins localized
      in pseudopodia cell protrusions. Astrocytes are the most abundant cell type in
      the CNS and typically extend long cellular protrusions. Increasing interest
      emerges concerning for example the growth mechanisms and functions of astrocytes
      in respect to brain development, re-uptake of neurotransmitters in the synaptic
      cleft and glial scar formation. Protein and RNA localization mechanisms have been
      extensively examined in neurons and shown to play pivotal roles for the
      functional presence of specific protein components in neuronal protrusions. Here
      we present a simple Boyden chamber based method to isolate astrocyte cell
      protrusions for biochemical analysis. We have succeeded in isolating protrusion
      localized RNA and protein from the mouse astrocyte cell line, C8-S, and mouse
      primary astrocytes. This is exemplified in biochemical analyses showing specific
      localization of the mRNA for Ras-related protein (Rab13), Plakophilin-4 (Pkp4),
      Ankyrin Repeat Domain 25 (Ankrd25), and inositol polyphosphate-1-phosphatase
      (Inpp1) in the protrusions of both C8-S cells and primary astrocytes. Concordant,
      the Pkp4 protein was also predominantly localized in the protrusions of C8-S and
      primary astrocytes. The described methodology can be the basis for both genome
      wide and specific descriptive and functional studies of RNA and protein
      localization in the protrusions of astrocytes which could contribute considerably
      to the existing knowledge of astrocyte functions in the CNS.

PMID- 21858872
TI  - Acetylcholine alpha7 nicotinic and dopamine D2 receptors are targeted to many of
      the same postsynaptic dendrites and astrocytes in the rodent prefrontal cortex.
AB  - The alpha-7 nicotinic acetylcholine receptor (alpha7nAChR) and the dopamine D(2)
      receptor (D(2) R) are both implicated in attentional processes and cognition,
      mediated in part through the prefrontal cortex (PFC). We examined the dual
      electron microscopic immunolabeling of alpha7nAChR and either D(2) R or the
      vesicular acetylcholine transporter (VAChT) in rodent PFC to assess convergent
      functional activation sites. Immunoreactivity (ir) for alpha7nAChR and/or D(2) R
      was seen in the same as well as separate neuronal and glial profiles. At least
      half of the dually labeled profiles were somata and dendrites, while most labeled
      axon terminals expressed only D(2) R-ir. The D(2) R-labeled terminals were
      without synaptic specializations or formed inhibitory or excitatory-type synapses
      with somatodendritic profiles, some of which expressed the alpha7nAChR and/or
      D(2) R. Astrocytic glial processes comprised the majority of nonsomatodendritic
      alpha7nAChR or alpha7nAChR and D(2) R-labeled profiles. Glial processes
      containing alpha7nAChR-ir were frequently located near VAChT-labeled terminals
      and also showed perisynaptic and perivascular associations. We conclude that in
      rodent PFC alpha7nACh and D(2) R activation can dually modulate (1) postsynaptic
      dendritic responses within the same or separate but synaptically linked neurons
      in which the D(2) R has the predominately presynaptic distribution, and (2)
      astrocytic signaling that may be crucial for synaptic transmission and functional
      hyperemia.

PMID- 21858876
TI  - In vitro modeling of central nervous system myelination and remyelination.
AB  - This review aims to summarize the current techniques to study myelination and
      remyelination in culture systems. We attempt to put these into historical
      context, and to identify the strengths and weaknesses of each approach, which
      vary depending on the experimental question to be tested. We discuss the
      difficulty and importance of quantification of myelination and in particular
      remyelination. Finally, we provide our predictions of how these techniques will
      and should develop in the future.

PMID- 21858877
TI  - Synthesis of indolizidines from optically pure alpha-amino acids via
      stereocontrolled rhodium-catalyzed hydroformylation of N-allylpyrroles.
AB  - Indolizidine alkaloids have attracted considerable attention because of their
      vast array of structural diversity and varied biological activity. This article
      relates the results that we obtained in the field of the total synthesis of
      indolizidines from alpha-amino acids, based on the rhodium-catalyzed
      hydroformylation of N-allylpyrroles intermediates. The formed pyrrolylbutanals
      undergo an intramolecular cyclodehydration to 5,6-dihydroindolizines, which are
      fully hydrogenated to indolizidines. All reaction sequences are stereocontrolled:
      indeed, the chiral center in the starting amino acid is transferred into 5,6
      dihydroindolizine moiety with complete stereochemical integrity and the new
      stereogenic center at C9 carbon atom in the final indolizidines is generated in
      only one configuration.

PMID- 21858878
TI  - Fabrication of metal-organic framework-containing silica-colloidal crystals for
      vapor sensing.

PMID- 21858879
TI  - Associations of age, gender and body mass with 1H MR-observed brain metabolites
      and tissue distributions.
AB  - Recent reports have indicated that a measure of adiposity, the body mass index
      (BMI), is associated with MR-observed brain metabolite concentrations and tissue
      volume measures. In addition to indicating possible associations between brain
      metabolism, BMI and cognitive function, the inclusion of BMI as an additional
      subject selection criterion could potentially improve the detection of metabolic
      and structural differences between subjects and study groups. In this study, a
      retrospective analysis of 140 volumetric MRSI datasets was carried out to
      investigate the value of including BMI in the subject selection relative to age
      and gender. The findings replicate earlier reports of strong associations of N
      acetylaspartate, creatine, choline and gray matter with age and gender, with
      additional observations of slightly increased spectral linewidth with age and in
      female relative to male subjects. Associations of metabolite levels, linewidth
      and gray matter volume with BMI were also observed, although only in some
      regions. Using voxel-based analyses, it was also observed that the patterns of
      the relative changes of metabolites with BMI matched those of linewidth with BMI
      or weight, and that residual magnetic field inhomogeneity and measures of
      spectral quality were influenced by body weight. It is concluded that, although
      associations of metabolite levels and tissue distributions with BMI occur, these
      may be attributable to issues associated with data acquisition and analysis;
      however, an organic origin for these findings cannot be specifically excluded.
      There is, however, sufficient evidence to warrant the inclusion of body weight as
      a subject selection parameter, secondary to age, and as a factor in data analysis
      for MRS studies of some brain regions.

PMID- 21858881
TI  - Aroma evaluation of gamazumi (Viburnum dilatatum) by aroma extract dilution
      analysis and odour activity value.
AB  - INTRODUCTION: Viburnum dilatatum (gamazumi) is widely distributed in Japan and
      China. Recently, juice from V. dilatatum fruits has been manufactured in Japan.
      Concerning the aroma of V. dilatatum, phenethyl alcohol, 3Z-hexenol and l
      linalool have been identified in the essential oil from the flowers of V.
      dilatatum, however, there are no detailed reports on the aroma of V. dilatatum
      elucidated using sensory evaluation. OBJECTIVE: To clarify odourants contributing
      to the characteristic aroma, the aroma extract dilution analysis (AEDA) method
      was performed through gas chromatography olfactometry (GC-O) analysis.
      METHODOLOGY: The aroma-active compounds were identified by GC-O and AEDA, and in
      order to determine the relative contribution of each compound to the aroma of V.
      dilatatum, odour activity value (OAV) has been used. RESULTS: The
      hydrodistillation of the leaf and branch of V. dilatatum afforded pale yellowish
      oils, with yields of 0.008 and 0.015% (w/w). The main components of the leaf oil
      were 3Z-hexenal (12.7%) and linalool (10.8%). In branch oil, palmitic acid
      (18.3%) and linoleic acid (8.2%) were identified. With regard to aroma
      components, 24 and 14 compounds were identified in the leaf and branch oils
      respectively, by GC-O analysis. CONCLUSION: On the basis of AEDA, OAVs and
      sensory evaluations, nonanal is estimated as the main aroma compound of leaf and
      branch oil, as the other aroma compounds, C6 compounds and 2-pentyl furan make
      green odour; linalool, eugenol and beta-ionone play important role in the sweet
      odour of leaf oil. In branch oil, cis-furanlinalool oxide and eugenol make sweet
      odour, and beta-eudesmol contributes to woody odour.

PMID- 21858880
TI  - A thin-layer chromatography method for the identification of three different
      olibanum resins (Boswellia serrata, Boswellia papyrifera and Boswellia carterii,
      respectively, Boswellia sacra).
AB  - INTRODUCTION: Resins of the genus Boswellia are currently an interesting topic
      for pharmaceutical research since several pharmacological activities (e.g. anti
      inflammatory, anti-microbial, anti-tumour) are reported for extracts and
      compounds isolated from them. Unambiguous identification of these resins, by
      simple and convenient analytical methods, has so far not clearly been verified.
      OBJECTIVE: For differentiation and identification of three important Boswellia
      species (Boswellia serrata Roxb., Boswellia papyrifera Hochst. and Boswellia
      carterii Birdw., respectively Boswellia sacra Flueck.), possible even for
      minimally equipped laboratories, a thin-layer chromatography (TLC) method was
      developed, allowing unambiguous identification of the three species. METHODOLOGY:
      Crude resin samples (commercial samples and a voucher specimen) were extracted
      with methanol or diethyl ether and subjected to TLC analysis (normal phase). A
      pentane and diethyl ether (2:1) with 1% acetic acid eluent was used.
      Chromatograms were analysed by UV detection (254 nm) and dyeing with anisaldehyde
      dyeing reagent. Significant spots were isolated and structures were assigned
      (mass spectrometry; nuclear magnetic resonance spectroscopy). RESULTS: Incensole
      and incensole acetate are specific biomarkers for Boswellia papyrifera. Boswellia
      carterii/Boswellia sacra reveal beta-caryophyllene oxide as a significant marker
      compound. Boswellia serrata shows neither incensole acetate nor beta
      caryophyllene oxide spots, but can be identified by a strong serratol and a sharp
      3-oxo-8,24-dien-tirucallic acid spot. CONCLUSION: The TLC method developed allows
      unambiguous identification of three different olibanum samples (Boswellia
      papyrifera, Boswellia serrata, Boswellia carterii/Boswellia sacra). Evidence on
      the specific biosynthesis routes of these Boswellia species is reported.

PMID- 21858882
TI  - Analysis of C-glycosyl flavonoids from South American Passiflora species by HPLC
      DAD and HPLC-MS.
AB  - INTRODUCTION: Leaves and fruits of Passiflora species are widely used around the
      world in popular medicine, mainly as sedatives and tranquilisers. C-glycosyl
      flavonoids are the main components of these species. OBJECTIVE: To investigate
      the constituent patterns and to develop a chromatographic method for the
      characterisation of the C-glycosyl flavonoids profile of the extracts of the
      leaves and the pericarp of South American Passiflora species. METHODOLOGY: The
      chemical composition of extracts from the leaves and the fruits' pericarp of
      Passiflora edulis var. flavicarpa, P. edulis var. edulis, Passiflora alata,
      Passiflora tripartita var. mollissima, Passiflora quadrangularis, Passiflora
      manicata and Passiflora ligularis was evaluated for the presence of C-glycosyl
      flavonoids. Two separate HPLC methods were developed suitable for a diode array
      detector (DAD) and a MS detector. Separation by HPLC-DAD was achieved on a Luna C
      18 column, using solvent A (tetrahydrofuran-isopropanol-acetonitrile) and solvent
      B (H3PO4 0.5%) in an isocratic elution mode. In the HPLC-MS, the components were
      separated on a Luna RP-18A column by a gradient elution (water-acetonitrile
      formic acid). RESULTS: The presence of C-glycosyl flavonoids was identified in
      leaves and pericarp of P. edulis var. flavicarpa, P. alata, P. edulis var. edulis
      and P. tripartita var. molissima, but only in leaf extracts of P. quadrangularis
      and P. manicata and not at all in P. ligularis. The different species and
      varieties showed different major constituents. The C-glycosyl flavonoids
      identified more frequently were orientin, isoorientin, vitexin and isovitexin.
      CONCLUSION: The methods established are simple and can be used as a tool for the
      characterisation and quality control of pharmaceutical preparations containing
      these Passiflora extracts.

PMID- 21858883
TI  - Gestational sac and embryonic growth are not useful as criteria to define
      miscarriage: a multicenter observational study.
AB  - OBJECTIVES: We studied changes in mean gestational sac diameter (MSD) and
      embryonic crown-rump length (CRL) in intrauterine pregnancies of uncertain
      viability (IPUVs). We aimed to establish cut-off values for MSD and CRL growth
      that could be definitively associated with either viability or miscarriage, and
      to establish the relationship between growth in MSD and appearance of embryonic
      structures in the gestational sac. METHODS: One thousand and sixty consecutive
      IPUVs were recruited prospectively from four London University hospitals: 462
      with no yolk sac or embryo, 419 with a yolk sac but no embryo, and 179 with an
      embryo but no heartbeat visible. IPUV was defined as an empty gestational sac
      with or without a yolk sac but no embryo seen with MSD < 20 or < 30 mm (depending
      on center) or an embryo with no heartbeat and CRL < 6 mm or < 8 mm (depending on
      center). Scans were repeated 7-14 days later. The endpoint was viability at first
      trimester screening ultrasonography between 11 and 14 weeks. Change in MSD and
      CRL between the first and second scans of each pregnancy was compared with
      respect to viability and appearance of embryonic structures using the two-sample
      t-test. RESULTS: The study included 359 pregnancies in which a gestational sac
      with or without embryo was identified at the follow-up scan 7-14 days later. Of
      these, 192 were viable and 167 non-viable at the 11-14-week scan. MSD growth was
      significantly higher in viable than non-viable pregnancies (mean 1.003 vs. 0.503
      mm/day; P < 0.001, 95% CI of difference 0.403-0.596). A difference in CRL growth
      was found between the two groups (mean 0.673 vs. 0.148 mm/day; P < 0.001, 95% CI
      of difference 0.345-0.703). MSD growth of 0.6 mm/day was associated with a
      specificity for diagnosing miscarriage of 90.1%, a sensitivity of 61.7% and 19
      false-positive test results. A cut-off of CRL growth rate of 0.2 mm/day gave a
      sensitivity of 76.3% and there were no false-positive test results for
      miscarriage. On repeat scan the failure of either a yolk sac or embryo to be
      visualized was always associated with miscarriage. CONCLUSION: There is an
      overlap in MSD growth rates between viable and non-viable IPUV. No cut-off exists
      for MSD growth below which a viable pregnancy could be safely excluded. A cut-off
      value for CRL growth of 0.2 mm/day was always associated with miscarriage. These
      data suggest that criteria to diagnose miscarriage based on growth in MSD and CRL
      are potentially unsafe. However, finding an empty gestational sac on two scans
      more than 7 days apart is highly likely to indicate miscarriage, irrespective of
      growth.

PMID- 21858884
TI  - Right aortic arch with patent right ductus arteriosus and normal heart.

PMID- 21858885
TI  - Standardized approach for imaging and measuring Cesarean section scars using
      ultrasonography.
AB  - Incomplete healing of the scar is a recognized sequel of Cesarean section (CS)
      and may be associated with complications in later pregnancies. These
      complications can include scar pregnancy, a morbidly adherent placenta, scar
      dehiscence or rupture. To date there is uncertainty relating to the factors that
      lead to poor scar healing and how to recognize it. In recent years, there has
      been an increase in studies using ultrasound that describe scars as deficient, or
      poorly, incompletely or inadequately healed with few data to associate the
      morphology of the scar with the functional integrity of the lower segment of the
      uterus. There have been multiple attempts to describe CS scars using
      ultrasonography. Different terminology, methods and results have been reported,
      yet there is still no consensus regarding the prevalence, clinical significance
      or most appropriate method to describe the appearances of these scars. Developing
      a test that can predict the likelihood of women having problems associated with a
      CS scar is becoming increasingly important. On the other hand, understanding
      whether the ultrasound appearances of the scar can tell us anything about its
      integrity is not well supported by the research evidence. In this article we
      present an overview of ultrasound-based definitions and methods used to describe
      CS scars. We also present information relating to the performance of alternative
      techniques used to evaluate CS scars. Having examined the current evidence we
      suggest a standardized approach to describe CS scars using ultrasound so that
      future studies can be meaningfully compared.

PMID- 21858886
TI  - Performance of third-trimester ultrasound for prediction of small-for-gestational
      age neonates and evaluation of contingency screening policies.
AB  - OBJECTIVES: To assess the performance of third-trimester fetal biometry and fetal
      Doppler studies for the prediction of small-for-gestational-age (SGA) neonates,
      and to explore contingency strategies using a first-trimester prediction model
      based on maternal and fetal parameters and third-trimester ultrasound. METHODS:
      This was an observational cross-sectional study of uncomplicated singleton
      pregnancies. Risk assessment for chromosomal abnormality was carried out in 4702
      pregnancies using a combination of ultrasound markers (fetal nuchal translucency
      thickness (NT) and nasal bone assessment) and biochemistry (free beta-human
      chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP
      A)) at 11 to 13 + 6 weeks. Maternal demographic characteristics and method of
      conception were recorded. Third-trimester (30-34 weeks) fetal biometry
      (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC)
      and femur length (FL)) and umbilical artery (UA) and middle cerebral artery
      Doppler studies were performed routinely in a subgroup (n = 2310). Reference
      ranges for birth weight were constructed using the cohort of 4702 women, and
      neonates were classified as small (SGA, <= 5th centile) or appropriate (AGA) for
      gestational age. First-trimester, third-trimester and integrated first- and third
      trimester prediction models for SGA were constructed using regression analysis
      and three different contingency strategies of rescanning in the third trimester
      were investigated. RESULTS: According to the areas under the receiver-operating
      characteristics curves (AUCs), AC (AUC = 0.85) and ultrasound-estimated fetal
      weight (EFW, AUC = 0.87) were equally good predictors of SGA. The model was
      marginally improved by the addition of UA Doppler, smoking status and first
      trimester indices (free beta-hCG and PAPP-A multiples of the median) (combined
      model, AUC = 0.88), but the difference was not statistically significant. A
      contingency strategy of rescanning 50% of the population in the third trimester
      according to the risk estimated by a first-trimester prediction model yielded a
      detection rate of 79% for a 25% screen-positive rate. CONCLUSION: Third-trimester
      ultrasound is effective in screening for SGA in uncomplicated pregnancies. The
      use of a contingency screening policy can reduce the need for unnecessary
      examinations.

PMID- 21858887
TI  - Computational analysis of residue contributions to coiled-coil topology.
AB  - A variety of features are thought to contribute to the oligomeric and topological
      specificity of coiled coils. In previous work, we examined the determinants of
      oligomeric state. Here, we examine the energetic basis for the tendency of six
      coiled-coil peptides to align their alpha-helices in antiparallel orientation
      using molecular dynamics simulations with implicit solvation (EEF1.1). We also
      examine the effect of mutations known to disrupt the topology of these peptides.
      In agreement with experiment, ARG or LYS at a or d positions were found to
      stabilize the antiparallel configuration. The modeling suggests that this is not
      due to a-a' or d-d' repulsions but due to interactions with e' and g' residues.
      TRP at core positions also favors the antiparallel configuration. Residues that
      disfavor parallel dimers, such as ILE at d, are better tolerated in, and thus
      favor the antiparallel configuration. Salt bridge networks were found to be more
      stabilizing in the antiparallel configuration for geometric reasons: antiparallel
      helices point amino acid side chains in opposite directions. However, the
      structure with the largest number of salt bridges was not always the most stable,
      due to desolvation and configurational entropy contributions. In tetramers, the
      extent of stabilization of the antiparallel topology by core residues is
      influenced by the e' residue on a neighboring helix. Residues at b and c
      positions in some cases also contribute to stabilization of antiparallel
      tetramers. This work provides useful rules toward the goal of designing coiled
      coils with a well-defined and predictable three-dimensional structure.

PMID- 21858889
TI  - Service dogs and people with physical disabilities partnerships: a systematic
      review.
AB  - Occupational therapists have recognized the benefits that service dogs can
      provide people with disabilities. There are many anecdotal publications extolling
      the benefits of working with service dogs, but few rigorous studies exist to
      provide the evidence of the usefulness of this type of assistive technology
      option. This systematic review evaluates the published research that supports the
      use of service dogs for people with mobility-related physical disabilities.
      Articles were identified by computerized search of PubMed, CINAHL, PsycINFO, OT
      Seeker, the Cochrane Database of Systematic Reviews, SportDiscus, Education
      Research Complete, Public Administration Abstracts, Web of Knowledge and Academic
      Search Premier databases with no date range specified. The keywords used in the
      search included disabled persons, assistance dogs or service dogs and mobility
      impairments. The reference lists of the research papers were checked as was the
      personal citation database of the lead author. Twelve studies met the inclusion
      criteria and whereas the findings are promising, they are inconclusive and
      limited because of the level of evidence, which included one Level I, six Level
      III, four Level IV and one Level V. All of the studies reviewed had research
      design quality concerns including small participant sizes, poor descriptions of
      the interventions, outcome measures with minimal psychometrics and lack of power
      calculations. Findings indicated three major themes including
      social/participation, functional and psychological outcomes; all of which are
      areas in the occupational therapy scope of practice. Occupational therapists may
      play a critical role in referral, assessment, assisting clients and consulting
      with training organizations before, during and after the service dog placement
      process. In order for health care professionals to have confidence in
      recommending this type of assistive technology, the evidence to support such
      decisions must be strengthened.

PMID- 21858888
TI  - Direct evidence that the carboxyl-terminal sequence of a bacterial chemoreceptor
      is an unstructured linker and enzyme tether.
AB  - Sensory adaptation in bacterial chemotaxis involves reversible methylation of
      specific glutamyl residues on chemoreceptors. The reactions are catalyzed by a
      dedicated methyltransferase and dedicated methylesterase. In Escherichia coli and
      related organisms, control of these enzymes includes an evolutionarily recent
      addition of interaction with a pentapeptide activator located at the carboxyl
      terminus of the receptor polypeptide chain. Effective enzyme activation requires
      not only the pentapeptide but also a segment of the receptor polypeptide chain
      between that sequence and the coiled-coil body of the chemoreceptor. This segment
      has features consistent with a role as a flexible and presumably unstructured
      linker and enzyme tether, but there has been no direct information about its
      structure. We used site-directed spin labeling and electron paramagnetic
      resonance spectroscopy to characterize structural features of the carboxyl
      terminal 40 residues of E. coli chemoreceptor Tar. Beginning ~ 35 residues from
      the carboxyl terminus and continuing to the end of the protein, spectra of spin
      labeled Tar embedded in native membranes or in reconstituted proteoliposomes,
      exhibited mobilities characteristic of unstructured, disordered segments. Binding
      of methyltransferase substantially reduced mobility for positions in or near the
      pentapeptide but mobility for the linker sequence remained high, being only
      modestly reduced in a gradient of decreasing effects for 10-15 residues, a
      pattern consistent with the linker providing a flexible arm that would allow
      enzyme diffusion within defined limits. Thus, our data identify that the carboxyl
      terminal linker between the receptor body and the pentapeptide is an
      unstructured, disordered segment that can serve as a flexible arm and enzyme
      tether.

PMID- 21858890
TI  - Thiol-alkyne chemistry for the preparation of micelles with glycopolymer corona:
      dendritic surfaces versus linear glycopolymer in their ability to bind to
      lectins.
AB  - A poly(tert-butyl acrylate) (P(tBA)) with a glycodendric endfunctionality with
      eight glucose moieties was synthesised in four steps via a combination of
      esterification, thiol-alkyne conjugation and hetero-Diels-Alder (HDA)
      cycloaddition. A linear glycopolymer of similar size and composition was also
      synthesised in order to compare the protein binding characteristics of the
      polymer with glycodendritic endfunctionality to the linear glycol blockcopolymer.
      The two amphiphilic polymers were self-assembled in water into micelles. These
      particles were then tested for their ability to bind to Concanavalin A (Con A).
      In a turbidity assay, the polymer glycodendron exhibited a significantly faster
      clustering rate to the lectin as compared to the linear glycopolymer. In a
      precipitation assay, it is found that significantly less glucose residue is
      required for binding per Con A for the polymer with the glycodendritic
      endfunctionality.

PMID- 21858891
TI  - One-step electro-spinning/netting technique for controllably preparing
      polyurethane nano-fiber/net.
AB  - Electro-spinning/netting (ESN) as a cutting-edge technique evokes much interest
      because of its ability in the one-step preparation of versatile nano-fiber/net
      (NFN) membranes. Here, a controllable fabrication of polyurethane (PU) NFN
      membranes with attractive structures, consisting of common electrospun nanofibers
      and two-dimensional (2D) soap bubble-like structured nano-nets via an ESN process
      is reported. The unique nanoscaled NFN architecture can be finely controlled by
      regulating the solution properties and several ESN process parameters. The
      versatile PU nano-nets comprising interlinked nanowires with ultrathin diameters
      (5-40 nm) mean that the NFN structured membranes possess several excellent
      characteristics, such as an extremely large specific surface area, high porosity
      and large stacking density, which would be particularly useful for applications
      in ultrafiltration, special protective clothing, ultrasensitive sensors, catalyst
      support and so on.

PMID- 21858893
TI  - New thiol-responsive mono-cleavable block copolymer micelles labeled with single
      disulfides.
AB  - Thiol-responsive symmetric triblock copolymers having single disulfide linkages
      in the middle blocks (called mono-cleavable block copolymers, ss-ABP(2)) were
      synthesized by atom transfer radical polymerization in the presence of a
      disulfide-labeled difunctional Br-initiator. These brush-like triblock copolymers
      consist of a hydrophobic polyacrylate block having pendent oligo(propylene oxide)
      and a hydrophilic polymethacrylate block having pendent oligo(ethylene oxide).
      Gel permeation chromatography and (1)H NMR results confirmed the synthesis of
      well-defined mono-cleavable block copolymers and revealed that polymerizations
      were well controlled. Because of amphiphilic nature, these copolymers self
      assembled to form colloidally stable micelles above critical micellar
      concentration of 0.032 mg . mL(-1). In response to reductive reactions,
      disulfides in thiol-responsive micelles were cleaved. Atomic force microscopy and
      dynamic light scattering analysis suggested that the cleavage of disulfides
      caused dissociation of micelles to smaller-sized assembled structures in water.
      Moreover, in a biomedical perspective, the mono-cleavable block copolymer
      micelles are not cytotoxic and thus biocompatible.

PMID- 21858892
TI  - Surface initiated polymerization on pulsed plasma deposited polyallylamine: a
      polymer substrate-independent strategy to soft surfaces with polymer brushes.
AB  - The deposition of polyallylamine (PAA) adlayers by pulsed plasma polymerization
      on various types of polymeric substrates has been explored as a general route to
      amino functionalized polymeric surfaces. These amino groups are highly suitable
      for anchoring an atom transfer radical polymerization (ATRP) initiator via a
      robust amide linkage. Subsequent surface initiated ATRP (SI-ATRP) of monomethoxy
      oligo(ethylene glycol) methacrylate (MeOEGMA) resulted in polyMeOEGMA brush
      grafted polymer surfaces. This combined strategy of pulsed plasma polymerization
      with SI-ATRP was demonstrated for five different polymeric substrates namely
      polyether ether ketone (PEEK), polyethylene terephthalate (PET), polyimide (PI),
      polypropylene (PP), and polytetrafluoroethylene (PTFE). Analysis of brush layers
      by attenuated total reflection infrared (ATR-IR) spectroscopy as well as X-ray
      photoelectron spectroscopy (XPS) fully corroborated the success of the proposed
      strategy for all substrate types.

PMID- 21858894
TI  - Facile and controlled fabrication of functional gold nanoparticle-coated
      polystyrene composite particle.
AB  - Gold nanoparticles-coated polystyrene (AuNPs-coated PS) composite particles with
      raspberry-like morphology are successfully prepared with the aid of a unique
      thermodynamically driving effect. It is of considerable interest that the AuNPs
      generate and self-assemble with raw, ordinary PS microspheres that preexist in
      the oxidation-reduction systems. The synthesized AuNPs-coated PS composite
      particles have been extensively characterized using scanning electron microscope,
      transmission electron microscope, and UV-Vis-NIR spectroscopy. The results
      indicate that the morphology of the resultant composite particles is governed by
      simply changing the amount and type of reductants and the concentration of PS
      microspheres. The AuNPs-coated PS composite particles also exhibit the good
      surface-enhanced Raman scattering and catalytic performances.

PMID- 21858895
TI  - Synthesis of eight-shaped poly(ethylene oxide) by the combination of Glaser
      coupling with ring-opening polymerization.
AB  - The eight-shaped poly(ethylene oxide) (PEO) is synthesized by a combination of
      Glaser coupling with ring-opening polymerization (ROP). Firstly, the star-shaped
      (PEO-OH)(4) is synthesized by ROP of ethylene oxide (EO) using pentaerythritol as
      an initiator and diphenylmethyl potassium (DPMK) as a deprotonated agent, and
      then the alkyne group is introduced onto the PEO arm-end to give (PEO-Alkyne)(4)
      in a NaH/tetrahydrofuran (THF) system. The intramolecular cyclization is carried
      out by a Glaser coupling reaction in a pyridine/CuBr/N,N,N',N",N"
      pentamethyldiethylenetriamine (PMDETA) system at room temperature in an air
      atmosphere, and eight-shaped PEO was formed with high efficiency (almost 100%).
      The target polymers and intermediates were well characterized by SEC, MALDI-TOF
      MS, (1)H NMR and FT-IR in detail.

PMID- 21858896
TI  - Hair lead levels to evaluate the subclinical impact of lead on growth in
      Sardinian children (Italy).
AB  - OBJECTIVES: The aim of this study was to determine if there are significant
      relationships between lead concentrations in children's hair and height, sitting
      height, and estimated leg length. METHODS: We analyzed three samples collected at
      different times: 1998, 2002, 2007. The total sample consisted of 825 children
      between 11 and 14 years of age living in different municipalities of Sardinia
      (Italy). Inductively coupled plasma atomic emission spectrometry (1998),
      inductively coupled plasma atomic absorption spectrometry (2002), and inductively
      coupled mass spectrometry (2007) were used to measure the lead concentration in
      hair (PbH). Some AAS measurements were also performed on the 1998 and 2007
      samples to check the reliability of the data. RESULTS: The mean PbH is much
      higher in 1998 (5.84 MUg/g) than in 2002 (1.49 MUg/g) and 2007 (0.78 MUg/g).
      Multivariate regression analysis of the three samples, controlling for age and
      sex, indicates a subclinical impact of lead on growth that differs according to
      the mean lead concentration in the hair. In fact, for 1998, the relationships
      between all three anthropometric variables and logPbH are significantly negative.
      For 2002, there are significant negative associations between height and
      estimated leg length and logPbH but not between sitting height and logPbH. For
      2007, there are not significant associations between logPbH and anthropometric
      variables. CONCLUSIONS: Our results support the use of hair lead levels as a
      biomarker to assess the impact of subclinical lead on the physical growth of
      children, especially when the study area presents medium and/or high levels of
      lead pollution.

PMID- 21858897
TI  - Pitfalls in meta-analyses on adverse events reported from clinical trials.
AB  - In recent years, comparative effectiveness research has been more aggressively
      pursued as a means to improve health care, including systematic reviews and meta
      analyses to inform health policy decision making. Because most clinical trials
      have pre-specified approaches to collecting data on efficacy, the value of
      systematic reviews and meta-analyses in assessing efficacy outcomes is generally
      accepted. In contrast, collection of data on adverse events is seldom well
      structured. Hence, the methodological considerations for comparing adverse events
      from such non-aligned sources differ substantially from those for comparing
      efficacy endpoints. We address several important pitfalls in performing
      systematic reviews and meta-analyses on adverse events in clinical trials, and we
      offer recommendations for remedies. Some pitfalls arise from the fact that
      adverse events often are not the primary endpoints in clinical trials, hence
      incomplete reporting, inconsistent event definitions, various level of effort in
      reporting unexpected adverse events, and inappropriate use of statistical
      testing. Others are posed by certain important characteristics of adverse events
      data. The very concept of "adverse events" may skew the ascertainment,
      attribution, and reporting of the events. In addition, problems for meta-analysis
      methods arise in situations involving zero or rare events and withdrawal or loss
      to follow-up because of adverse events. We highlight recent initiatives that may
      improve the assessment and cross-study summary of adverse events. We anticipate
      that future guidance for conducting systematic reviews and meta-analyses will
      evolve to address the important methodological pitfalls we highlight here, and
      the practice of assessing the totality of evidence on drug safety will be
      improved.

PMID- 21858898
TI  - National changes in oral antipsychotic treatment for people with schizophrenia in
      primary care between 1998 and 2007 in the United Kingdom.
AB  - PURPOSE: There is little information regarding antipsychotic prescription in
      primary care, despite general practitioners issuing most ongoing prescriptions.
      We sought to investigate changes in oral antipsychotic prescriptions in primary
      care from January 1998 to December 2007. METHODS: We conducted a cohort analysis
      of patients diagnosed with schizophrenia in primary care in the United Kingdom,
      using The Health Improvement Network database, to determine the proportions of
      prescribed antipsychotics. We investigated the yearly estimates of the overall
      time patients spent in treatment with any antipsychotic as well as the class of
      antipsychotic and individual antipsychotic agent. RESULTS: We found that in any
      one calendar year, approximately 24% of patients previously prescribed
      antipsychotics do not receive treatment in primary care. Over the last decade,
      people with schizophrenia have been prescribed antipsychotic treatment for
      greater proportions of time. The greatest increase was observed in older women.
      The overall increase in treatment time can be attributed to the increased
      prescription of second-generation antipsychotics (SGAs). The annual proportion of
      time in SGA treatment increased from 16.6% to 51.2% within the study period,
      whereas time in first-generation antipsychotic treatment reduced from 37.1% to
      15.0%. Overall, olanzapine, risperidone and sulpiride were prescribed for the
      longest periods of time. CONCLUSIONS: Over the last decade, the general practice
      of prescribing SGAs has increased whereas first-generation antipsychotic
      prescriptions have declined. By 2007, patients with schizophrenia were prescribed
      antipsychotics for greater proportions of time, perhaps reflecting the greater
      acceptability of SGAs or a shift from secondary to primary care prescription.

PMID- 21858899
TI  - Discrepancies between the electronic medical record, the prescriptions in the
      Swedish national prescription repository and the current medication reported by
      patients.
AB  - PURPOSE: To study discrepancies between (i) the prescribed current treatment
      stated by patients with congestive heart failure (CHF) compared with patients
      with other chronic diseases, (ii) the data in the medication list (ML) in the
      electronic medical record and (iii) the data in the prescription list (PL) on the
      prescriptions stored in the national prescription repository in Sweden, to
      determine current, noncurrent, duplicate and missing prescriptions. METHODS: At
      one healthcare centre, a random sample of patients 18 years and older with a
      diagnosis of CHF, diabetes mellitus (DM) or osteoarthritis (OA) provided written
      informed consent to participate. Participants were interviewed by telephone on
      the prescribed current treatment. RESULTS: Of 161 invited patients (61 CHF, 50 DM
      and 50 OA), 66 patients were included. More than 80% of the patients had at least
      one discrepancy, a noncurrent, a duplicate or a missing prescription, in the ML
      and PL. The overall congruence for unique prescriptions on current treatment
      between the ML and the PL was only 55%. Patients with CHF had overall more
      discrepancies and patients with DM fewer discrepancies in the ML. CONCLUSIONS:
      Prescriptions for noncurrent treatment, duplicates and missing prescriptions are
      common in both the ML in the electronic medical record and the list on
      prescriptions stored in the Swedish National Prescription Repository. Patients
      with CHF had more discrepancies in the ML. The risk for medication errors in
      primary care due to incorrect information on prescribed treatment may be
      substantial.

PMID- 21858900
TI  - Biosensor Forster resonance energy transfer detection by the phasor approach to
      fluorescence lifetime imaging microscopy.
AB  - We present here the phasor approach to biosensor Forster resonance energy
      transfer (FRET) detection by fluorescence lifetime imaging microscopy (FLIM) and
      show that this method of data representation is robust towards biosensor design
      as well as the fluorescence artifacts inherent to the cellular environment. We
      demonstrate this property on a series of dual and single chain biosensors, which
      report the localization of Rac1 and RhoA activity, whilst performing concomitant
      ratiometric FRET analysis on the acquired FLIM data by the generalized
      polarization (GP) approach. We then evaluate and compare the ability of these two
      methods to quantitatively image biosensor FRET signal as a function of time and
      space. We find that with lifetime analysis in the phasor plot each molecular
      species is transformed into a two-dimensional coordinate system where independent
      mixtures of fluorophores can be distinguished from changes in lifetime due to
      FRET. This enables the fractional contribution of the free and bound state of a
      dual chain biosensor or the low and high FRET species of a single chain biosensor
      to be quantified in each pixel of an image. The physical properties intrinsic to
      each biosensor design are also accurately characterized by the phasor analysis;
      thus, this method could be used to inform biosensor optimization at the
      developmental stage. We believe that as biosensors become more sophisticated and
      are multiplexed with other fluorescent molecular tools, biosensor FRET detection
      by the phasor approach to FLIM will not only become imperative to their use but
      also their advancement.

PMID- 21858901
TI  - The photoreceptive cells of the pineal gland in adult zebrafish (Danio rerio).
AB  - The zebrafish pineal gland plays a fundamental role in the regulation of the
      circadian rhythm through the melatonin secretion. The pinealocytes, also called
      photoreceptive cells, are considered the morphofunctional unit of pineal gland.
      In literature, the anatomical features, the cellular characteristics, and the
      pinealocytes morphology of zebrafish pineal gland have not been previously
      described in detail. Therefore, this study was undertaken to analyze the
      structure and ultrastructure, as well as the immunohistochemical profile of the
      zebrafish pineal gland with particular reference to the pinealocytes. Here, we
      demonstrated, using RT-PCR, immunohistochemistry and transmission electron
      microscopy, the expression of the mRNA for rhodopsin in the pineal gland of
      zebrafish, as well as its cellular localization exclusively in the pinealocytes
      of adult zebrafish. Moreover, the ultrastructural observations demonstrated that
      the pinealocytes were constituted by an outer segment with numerous lamellar
      membranes, an inner segment with many mitochondria, and a basal pole with the
      synapses. Our results taken together demonstrated a central role of zebrafish
      pinealocytes in the control of pineal gland functions.

PMID- 21858902
TI  - [P(MU-NTer)]2: a biradicaloid that is stable at high temperature.

PMID- 21858904
TI  - Nickel-catalyzed cycloaddition of alpha,beta,gamma,delta-unsaturated ketones with
      alkynes.

PMID- 21858903
TI  - Depolymerization of cellulose assisted by a nonthermal atmospheric plasma.

PMID- 21858905
TI  - Ruthenium-catalyzed coupling of oxabenzonorbornadienes with alkynes bearing a
      propargylic oxygen atom: access to stereodefined benzonorcaradienes.

PMID- 21858906
TI  - A highly enantioselective one-pot synthesis of spirolactones by an
      organocatalyzed Michael addition/cyclization sequence.

PMID- 21858907
TI  - Sponge biosilica formation involves syneresis following polycondensation in vivo.
AB  - Syneresis is a process observed during the maturation/aging of silica gels
      obtained by sol-gel synthesis that results in shrinkage and expulsion of water
      due to a rearrangement and increase in the number of bridging siloxane bonds.
      Here we describe how the process of biosilica deposition during spicule
      ("biosilica" skeleton of the siliceous sponges) formation involves a phase of
      syneresis that occurs after the enzyme-mediated polycondensation reaction.
      Primmorphs from the demosponge Suberites domuncula were used to study syneresis
      and the inhibition of this mechanism. We showed by scanning electron microscopy
      that spicules added to primmorphs that have been incubated with manganese sulfate
      fuse together through the deposition of silica spheres and bridges. Energy
      dispersive X-ray mapping of the newly formed deposits showed high silicon and
      oxygen content. These biosilica deposits contain a comparably higher percentage
      of water than mature/aged spicules. Quantitative real-time polymerase chain
      reaction analyses revealed that the addition of silicate to primmorph cultures
      resulted in a marked upregulation of the expression of the aquaporin gene and of
      the genes encoding the silica anabolic enzyme silicatein-alpha and the silica
      catabolic enzyme silicase. On the other hand, addition of manganese sulfate,
      either alone or together with silicate, caused a strong reduction in the level of
      aquaporin transcripts, although this metal ion did not essentially affect the
      silicate-induced increase in silicatein-alpha and silicase gene expression. We
      conclude that the secondary silica deposits formed on spicules under
      physiological conditions in the presence of silicate fuse together and
      subsequently undergo syneresis, which is facilitated by the removal of water
      through aquaporin channels. In growing spicules, these processes of biosilica
      formation and syneresis in the lamellar monolithic structures precede the final
      step of "biosintering" during which the massive biosilica rods of the spicules
      are formed.

PMID- 21858908
TI  - Two-photon STED spectral determination for a new V-shaped organic fluorescent
      probe with efficient two-photon absorption.
AB  - Two-photon stimulated emission depletion (STED) cross sections were determined
      over a broad spectral range for a novel two-photon absorbing organic molecule,
      representing the first such report. The synthesis, comprehensive linear
      photophysical, two-photon absorption (2PA), and stimulated emission properties of
      a new fluorene-based compound, (E)-2-{3-[2-(7-(diphenylamino)-9,9-diethyl-9H
      fluoren-2-yl)vinyl]-5-methyl-4-oxocyclohexa-2,5-dienylidene} malononitrile (1),
      are presented. Linear spectral parameters, including excitation anisotropy and
      fluorescence lifetimes, were obtained over a broad range of organic solvents at
      room temperature. The degenerate two-photon absorption (2PA) spectrum of 1 was
      determined with a combination of the direct open-aperture Z-scan and relative two
      photon-induced fluorescence methods using 1 kHz femtosecond excitation. The
      maximum value of the 2PA cross section ~1700 GM was observed in the main, long
      wavelength, one-photon absorption band. One- and two-photon stimulated emission
      spectra of 1 were obtained over a broad spectral range using a femtosecond pump
      probe technique, resulting in relatively high two-photon stimulated emission
      depletion cross sections (~1200 GM). A potential application of 1 in bioimaging
      was demonstrated through one- and two-photon fluorescence microscopy images of
      HCT 116 cells incubated with micelle-encapsulated dye.

PMID- 21858909
TI  - Insecticide selectivity to two species of Trichogramma in three different hosts,
      as determined by IOBC/WPRS methodology.
AB  - BACKGROUND: The use of Trichogramma species is a potential key strategy in
      integrated pest management. However, its effectiveness depends on the use of
      chemicals that do not interfere with parasitism and parasite population growth.
      Here, a study was made of the effects of synthetic insecticides on Trichogramma
      pretiosum and Trichogramma exiguum in different hosts (Ephestia kuehniella,
      Plutella xylostella and Spodoptera frugiperda) and the influence of International
      Organisation for Biological Control (IOBC/WPRS) methodology in selectivity
      studies using different Trichogramma species. The insecticides used were
      commercial formulations (triflumuron at a concentration of 0.2 mL L(-1) water,
      etofenprox at a concentration of 0.47 mL L(-1) water and endosulfan at a
      concentration of 7.5 mL L(-1) water); the control treatment consisted of
      distilled water. Eggs attached to cardboard cards were offered to parasitoids
      inside glass cages. Parasitised eggs, parasitism and adult emergence rates and
      parasitism reduction were evaluated. RESULTS: Endosulfan and etofenprox,
      classified as class-4 toxic products, were extremely toxic to the parasitoids.
      Triflumuron, classified as a non-toxic product, was selective to the parasitoids
      in eggs of all hosts. CONCLUSIONS: The methodology recommended by IOBC/WPRS
      influenced results regarding the use of different species of parasitoids, and the
      use of a single parasitoid species in their experiment is questionable.

PMID- 21858910
TI  - Cross-resistance patterns and fitness in fufenozide-resistant diamondback moth,
      Plutella xylostella (Lepidoptera: Plutellidae).
AB  - BACKGROUND: Fufenozide is a novel non-steroidal ecdysone agonist with good
      efficacy against diamondback moth (DBM), Plutella xylostella (Lepidoptera:
      Plutellidae). At present, it is widely applied for the control of a range of
      lepidopterous pests in China. This study compared the activities of fufenozide
      and 12 other insecticides against unselected and fufenozide-selected strains of
      DBM to examine potential patterns of cross-resistance. The relative fitness of
      the fufenozide-selected strain was assessed to provide information pertinent to
      insecticide resistance management. RESULTS: Compared with the susceptible strain
      (JSS), the fufenozide-resistant strain (JSR) showed high cross-resistance to
      dibenzoylhydrazines and benzoylphenylureas, low cross-resistance to abamectin and
      no cross-resistance to organophosphates, carbamates and pyrethroids. JSR had a
      lower reproductive ability and a relative fitness of 0.5 compared with JSS.
      CONCLUSION: P. xylostella has the potential to develop resistance to fufenozide,
      albeit at the expense of fitness. Cross-resistance between the same and other
      classes of insecticides is of concern, and should be a key consideration when
      implementing fufenozide-based control strategies for this species.

PMID- 21858911
TI  - Acromyrmex octospinosus (Hymenoptera: Formicidae) management. Part 1: Effects of
      TRAMIL's insecticidal plant extracts.
AB  - BACKGROUND: Leaf-cutting ants are considered to be one of the most important pest
      species of the New World. Until now, control strategies against these leaf
      cutting ants have mainly been synthetic chemicals. The aim of the present study
      was to test the action of several plant extracts quoted as an example by TRAMIL
      participative surveys for their insecticidal properties on adult major workers of
      Acromyrmex octospinosus. Three tests were used to that end: contact toxicity,
      repellent test and ingestion bioassay. Six traditional plant uses recommended by
      interviewed people in surveys were tested: (1) maceration of Mammea americana
      fresh crushed seeds; (2) decoction of Nerium oleander fresh leaves; (3) Nerium
      oleander dried leaf water juice; (4) decoction of Nicotiana tabacum dried leaves;
      (5) Trichillia pallida dried leaf water juice; (6) decoction of Rollinia mucosa
      dried seeds. RESULTS: Two plant extracts with contact toxicity (Mammea americana
      and Nicotiana tabacum), six plant extracts with repellent activity and four plant
      extracts with ingestion toxicity (Mammea americana, Nicotiana tabacum and both
      extracts of Nerium oleander) were found. CONCLUSION: The data presented in this
      study showed that plant extracts cited by TRAMIL ethnopharmacological surveys
      have the potential to control the leaf-cutting ant, Acromyrmex octospinosus. In
      particular, the Mammea americana extract, with its natural low repellent effect
      and its high toxicity by ingestion, and Nerium oleander extracts, with their
      natural delay action, are possibly the best extracts for the control of these
      ants.

PMID- 21858912
TI  - Toward optimizing the indications for orthotopic liver transplantation in
      hepatocellular carcinoma.
AB  - KEY POINTS: 1. Liver transplantation is currently an effective therapy for
      patients with HCC who meet the Milan criteria. 2. The proportion of patients on
      waiting lists for liver transplantation who have HCC has increased substantially
      in recent years. HCC is currently one of the major indications for liver
      transplantation; it is the indication for approximately one-third of liver
      transplants. 3. If the Milan criteria are not met, the survival rates after liver
      transplantation for HCC tend to decrease, mainly because of the catastrophic
      consequences of HCC recurrence. 4. A few studies have supported liver
      transplantation when the Milan criteria are exceeded, but extensions beyond the
      Milan criteria remain controversial. Even if an individual patient with HCC who
      does not meet the Milan criteria might benefit from liver transplantation, the
      limited number of currently available donor organs limits the indications for
      liver transplantation to those patients with HCC who have the greatest likelihood
      of survival after the procedure. 5. To patients with early-stage HCC, surgical
      resection can be offered if the hepatocellular function is well maintained and
      severe portal hypertension is not present. 6. To enable patients with HCC to have
      access to liver transplantation that is similar to the access for other patients
      without HCC in the MELD allocation system, additional points based on the number
      and size of HCC lesions are assigned to patients on the waiting list. However,
      this system requires further refinement to ensure that it is as fair as possible.
      7. Liver transplantation for HCC should be restricted to those patients who are
      expected to have the same posttransplant survival as that of patients with
      nonneoplastic end-stage chronic liver disease. 8. On the basis of these
      considerations, a 5-year survival rate of 50% after liver transplantation for HCC
      seems too low.

PMID- 21858913
TI  - Hepatic blood flow plays an important role in ischemia-reperfusion injury.
AB  - Severe ischemia/reperfusion (IR) injury is associated with poor hepatic
      microperfusion. The aim of this study was to investigate the role of hepatic
      artery flow (HAF) and portal vein flow (PVF) in IR injury. From January 2004 to
      June 2008, 566 patients underwent orthotopic liver transplantation (OLT). The
      data were retrospectively reviewed via the transplant database. Patients with
      hepatic artery (HA) or portal vein (PV) thrombosis and retransplant patients were
      excluded. Intraoperative PVF and HAF values and graft weights were measured
      routinely, and the central venous pressure, mean arterial pressure, cardiac
      output, and cardiac index were recorded with hepatic blood flow measurements.
      Complete data were available for 312 primary OLT recipients (215 males and 97
      females; mean age = 54 +/- 10 years). The patients' follow-up ranged from 215 to
      1746 days (705 +/- 408 days). IR injury was defined by the aspartate
      aminotransferase (AST) level on postoperative day (POD) 2, and the patients were
      divided into 3 groups: (1) mild IR injury [AST < 500 U/L; n = 160 (51%)], (2)
      moderate IR injury [AST = 500-1000 U/L; n = 85 (27%)], and (3) severe IR injury
      [AST > 1000 U/L; n = 67 (21%)]. The demographics and pre-OLT variables (the Model
      for End-Stage Liver Disease score (MELD), platelet counts, PV thrombosis,
      transjugular intrahepatic portosystemic shunts, and shunts on computed tomography
      scans) were similar in all groups. The graft survival rate was 99% in group 1,
      95.2% in group 2 (P = 0.02), and 92.3% in group 3 (P = 0.016). The patient
      survival rates were similar in the 3 groups. The cold ischemia time (CIT) was
      significantly higher in group 3 versus group 1 (P < 0.007). In the statistical
      analysis, low HAF, PVF, total liver blood flow (TLBF), and augmented HAF values
      were associated with a greater likelihood of elevated AST levels on POD 2. The
      strongest univariate predictors of AST were reduced augmented HAF (mL/minute/100
      g) values (P < 0.001) and reduced TLBF (mL/minute/100 g) values (P < 0.001). In a
      covariate analysis with adjustments for CIT and donor variables, the blood flow
      parameters remained important predictors of graft function. In conclusion, this
      report demonstrates for the first time that reduced hepatic blood flow is a
      significant finding in patients with severe hepatic IR injury.

PMID- 21858914
TI  - A revision of the intensity of treatment rating scale: classifying the intensity
      of pediatric cancer treatment.
AB  - BACKGROUND: We previously developed a reliable and valid method for classifying
      the intensity of pediatric cancer treatment. The Intensity of Treatment Rating
      Scale (ITR-2.0) 1 classifies treatments into four operationally defined levels of
      intensity and is completed by pediatric oncology specialists based on diagnosis,
      stage, and treatment data from the medical record. Experience with the ITR-2.0
      and recent changes in treatment protocols indicated the need for a minor revision
      and revalidation. METHODS: Five criterion raters reviewed the prior items,
      independently proposing additions and/or changes in the classification of
      diseases/treatments. Subsequent to a group discussion of the proposed changes, a
      revised 43-item ITR was evaluated. Pediatric oncologists (n = 47) completed a two
      part online questionnaire. Validity of the classifications was determined by the
      oncologists classifying each disease/treatment into one of the four levels of
      intensity. Inter-rater reliability was calculated by having each oncologist
      classify the treatments of 12 sample patients using the new version which we call
      the ITR-3. RESULTS: Agreement between median ratings of the 43 items for the
      pediatric oncologists and the criterion raters was high (r = 0.88). The median of
      the raters was either identical (81%) with the criterion ratings or discrepant by
      one level. Inter-rater reliability was very high when using the ITR-3 to classify
      12 sample patients, with a median agreement of 0.90 and an intraclass correlation
      coefficient (r(ICC) = 0.86). CONCLUSIONS: With these minor modifications and
      updates, the ITR-3 remains a reliable and valid method for classifying pediatric
      oncology treatment protocols.

PMID- 21858915
TI  - Response of murine bone marrow-derived mesenchymal stromal cells to dry-etched
      porous silicon scaffolds.
AB  - Porous silicon shows great promise as a bio-interface material due to its large
      surface to volume ratio, its stability in aqueous solutions and to the ability to
      precisely regulate its pore characteristics. In the current study, porous silicon
      scaffolds were fabricated from single crystalline silicon wafers by a novel xenon
      difluoride dry etching technique. This simplified dry etch fabrication process
      allows selective formation of porous silicon using a standard photoresist as mask
      material and eliminates the post-formation drying step typically required for the
      wet etching techniques, thereby reducing the risk of damaging the newly formed
      porous silicon. The porous silicon scaffolds supported the growth of primary
      cultures of bone marrow derived mesenchymal stromal cells (MSC) plated at high
      density for up to 21 days in culture with no significant loss of viability,
      assessed using Alamar Blue. Scanning electron micrographs confirmed a dense lawn
      of cells at 9 days of culture and the presence of MSC within the pores of the
      porous silicon scaffolds.

PMID- 21858916
TI  - Chondrogenic differentiation of adult mesenchymal stem cells and embryonic cells
      in collagen scaffolds.
AB  - Many cell types and cellular microenvironments have been explored for articular
      cartilage tissue engineering. We compared the potential of bone marrow-derived
      mesenchymal stem cells (MSCs) and P19 embryonic carcinoma cells (ECCs), a
      pluripotent derivative of embryonic stem cells (ESCs), for cartilage histogenesis
      in porous collagen scaffolds in vitro. We found that while both MSCs and ECCs
      express alpha-smooth muscle actin (alpha-SMA), only MSCs exhibit condensation and
      contraction necessary for cartilage histogenesis. Furthermore, histology
      confirmed that only MSCs exhibited sulfated glycosaminoglycans and collagen type
      II formation after 14 days in culture. We conclude that MSCs appear to be
      superior over ECCs for cartilage regeneration under particular culture
      conditions. The alpha-SMA-expressing ECCs may not have contracted due to the
      absence of actin unit polymerization or the absence of myosin molecules. Our
      observations may explain the absence of a contractile scar in fetal wound
      healing.

PMID- 21858917
TI  - Development and characterization of an acellular porcine cartilage bone matrix
      for use in tissue engineering.
AB  - The aim of this study was to develop a technique to decellularize a porcine
      cartilage bone construct with view to using this as a biological scaffold for
      cartilage substitution. The decellularization protocol applied freeze/thaw
      cycles; this was followed by cyclic incubation in hypotonic tris buffer and 0.1%
      (w/v) sodium dodecyl sulfate in hypotonic buffer plus protease inhibitors.
      Nucleases (RNase and DNase) were used to digest nucleic acids followed by
      disinfection using 0.1% (v/v) peracetic acid. Histological analysis confirmed the
      absence of visible cells within the decellularized tissue. DNA analysis revealed
      the near-complete removal of genomic DNA from the decellularized tissues. The
      decellularization process had minimal effect on the collagen content of the
      cartilage. However, there was a significant reduction in the glycosaminoglycan
      content in the decellularized tissues. There was no evidence of the expression of
      the major xenogeneic epitope, galactose-alpha-1,3-galactose. Biomechanical
      indentation testing of decellularized tissues showed a significant change in
      comparison to the fresh cartilage. This was presumed to be caused by the
      reduction in the glycosaminoglycan content. Biocompatibility of the acellular
      scaffold was determined using contact cytotoxicity assays and a
      galactosyltransferase knockout mouse model. Decellularized porcine cartilage
      tissue was found to exhibit favorable compatibility in both in vitro and in vivo
      tests. In conclusion, this study has generated data on the production of an
      acellular cartilage bone matrix scaffold for use in osteochondral defect repair.
      To our knowledge, this is the first study that has successfully removed whole
      cells and alpha-gal from xenogeneic cartilage and bone tissue.

PMID- 21858918
TI  - Effects of TiO2-containing phosphate glasses on solubility and in vitro
      biocompatibility.
AB  - Phosphate-based glasses with different amounts of titanium dioxide (TiO(2)),
      having the following molar composition 50P(2)O(5)-30CaO-9Na(2)O-3SiO(2)-3MgO-(5
      x)K(2)O-xTiO(2), (where x = 0, 2.5, 5 mol %), were synthesised and characterized
      in terms of solubility (according to ISO 10993-14), and in vitro biocompatibility
      using human MG-63 osteoblast cells. Dissolution tests were carried out in Tris
      HCl (pH 7.4) to simulate the physiological pH and in citric acid (pH 3.0) to
      simulate an acidic environment. The weight loss decreased with increasing TiO(2)
      content, a process further enhanced in acidic medium. TiO(2) reduced the pH
      changes usually caused by the dissolution products released. Cellular tests
      showed that all the glasses studied (0-5 mol % TiO(2)) and TiCl(4), used to
      investigate the biocompatibility of titanium ions, did not produce cytotoxic
      effects on human MG-63 osteoblasts for up to 5 days in culture. On the basis of
      these results, we suggest that TiO(2)-containing phosphate glasses could be
      promising substrates for bone tissue engineering applications.

PMID- 21858919
TI  - Optimized conditions for mesenchymal stem cells to differentiate into osteoblasts
      on a collagen/hydroxyapatite matrix.
AB  - Collagen/hydroxyapatite (HA) composite scaffolds are known to be suitable
      scaffolds for seeding with mesenchymal stem cells (MSCs) differentiated into
      osteoblasts and for the in vitro production of artificial bones. However, the
      optimal collagen/HA ratio remains unclear. Our study confirmed that a higher
      collagen content increased scaffold stiffness but that a greater stiffness was
      not sufficient for bone tissue formation, a complex process evidently also
      dependent on scaffold porosity. We found that the scaffold pore diameter was
      dependent on the concentration of collagen and HA and that it could play a key
      role in cell seeding. In conclusion, the optimal scaffold for new bone formation
      and cell proliferation was found to be a composite scaffold formed from 50 wt %
      HA in 0.5 wt % collagen I solution.

PMID- 21858924
TI  - Cytometry for improving and tailoring cancer therapy.

PMID- 21858920
TI  - SLC9A9 mutations, gene expression, and protein-protein interactions in rat models
      of attention-deficit/hyperactivity disorder.
AB  - SLC9A9 (solute carrier family 9, member 9, also known as Na+/H+ exchanger member
      (NHE9)) is a membrane protein that regulates the luminal pH of the recycling
      endosome, an essential organelle for synaptic transmission and plasticity. SLC9A9
      has been implicated in human attention deficit hyperactivity disorder (ADHD) and
      in rat studies of hyperactivity. We examined the SLC9A9 gene sequence and
      expression profile in prefrontal cortex, dorsal striatum and hippocampus in two
      genetic rat models of ADHD. We report two mutations in a rat model of inattentive
      ADHD, the WKY/NCrl rat, which affect the interaction of SLC9A9 with calcineurin
      homologous protein (CHP). We observed an age-dependent abnormal expression of
      SLC9A9 in brains of this inattentive model and in the Spontaneous Hypertensive
      Rat (SHR) model of ADHD. Our data suggest a novel mechanism whereby SLC9A9
      sequence variants and abnormalities in gene expression could contribute to the
      ADHD-like symptoms of rat models and possibly the pathophysiology of ADHD in
      humans.

PMID- 21858925
TI  - Nanoscience and nanotechnology: evolving definitions and growing footprint on the
      scientific landscape.

PMID- 21858921
TI  - Indexing disease progression at study entry with individuals at-risk for
      Huntington disease.
AB  - The identification of clinical and biological markers of disease in persons at
      risk for Huntington disease (HD) has increased in efforts to better quantify and
      characterize the epoch of prodrome prior to clinical diagnosis. Such efforts are
      critical in the design and implementation of clinical trials for HD so that
      interventions can occur at a time most likely to increase neuronal survival and
      maximize daily functioning. A prime consideration in the examination of prodromal
      individuals is their proximity to diagnosis. It is necessary to quantify
      proximity so that individual differences in key marker variables can be properly
      interpreted. We take a data-driven approach to develop an index that can be
      viewed as a proxy for time to HD diagnosis known as the CAG-Age Product Scaled or
      CAP(S) . CAP(S) is an observed utility variable computed for all genetically at
      risk individuals based on age at study entry and CAG repeat length. Results of a
      longitudinal receiver operating characteristic (ROC) analysis showed that CAP(S)
      had a relatively strong ability to predict individuals who became diagnosed,
      especially in the first 2 years. Bootstrap validation provided evidence that
      CAP(S) computed on a new sample from the same population could have similar
      discriminatory power. Cutoffs for the empirical CAP(S) distribution can be used
      to create a classification for mutation-positive individuals (Low-Med-High),
      which is, useful for comparison with the naturally occurring mutation-negative
      Control group. The classification is an improvement over the one currently in use
      as it is based on observed data rather than model-based estimated values. (c)
      2011 Wiley-Liss, Inc.

PMID- 21858926
TI  - Sol-gel substrates with engineered multiple photonic bandgaps for full-color
      photonic devices.

PMID- 21858927
TI  - Food-grade gene expression in lactic acid bacteria.
AB  - In the 1990s, significant efforts were invested in the research and development
      of food-grade expression systems in lactic acid bacteria (LAB). At this time,
      Lactococcus lactis in particular was demonstrated to be an ideal cell factory for
      the food-grade production of recombinant proteins. Steady progress has since been
      made in research on LAB, including Lactococcus, Lactobacillus and Streptococcus,
      in the areas of recombinant enzyme production, industrial food fermentation, and
      gene and metabolic pathway regulation. Over the past decade, this work has also
      led to new approaches on chromosomal integration vectors and host/vector systems.
      These newly constructed food-grade gene expression systems were designed with
      specific attention to self-cloning strategies, food-grade selection markers,
      plasmid replication and chromosomal gene replacements. In this review, we discuss
      some well-characterized chromosomal integration and food-grade host/vector
      systems used in LAB, with a special focus on sustainability, stability and
      overall safety, and give some attractive examples of protein expression that are
      based on these systems.

PMID- 21858929
TI  - Non-governmental organizations, democracy, and HIV prevalence: a cross-national
      analysis.
AB  - Despite the scale, reach, and global impact of the human immunodeficiency virus
      (HIV), its study has remained largely at the purview of various micro-level
      analyses (e.g., Gutmann 2007; Levi and Vitoria 2002). However, differences in
      prevalence rates at the national level suggest that other forces might be at
      work. Following the work of McIntosh and Thomas (2004), the only cross-national
      study of HIV/AIDS published to our knowledge, we conduct a cross-national
      analysis that examines world polity ideas that higher levels of health and
      women's non-governmental organizations (NGOs) should be associated with lower
      levels of HIV prevalence. Initially, we find no support for these hypotheses.
      However, we respecify our models to test a political opportunity structure
      hypothesis that democracy enhances the ability of health and women's NGOs to deal
      with HIV. We test this line of reasoning by including an interaction term between
      democracy and the health and women's NGO variables. In doing so, we find that
      health and women's NGOs are associated with lower levels of HIV prevalence in
      democratic rather than repressive nations.

PMID- 21858928
TI  - Dynamic responses of Xenopus retinal ganglion cell axon growth cones to netrin-1
      as they innervate their in vivo target.
AB  - Netrin-1 influences retinal ganglion cell (RGC) axon pathfinding and also
      participates in the branching and synaptic differentiation of mature RGC axons at
      their target. To investigate whether netrin also serves as an early target
      recognition signal in the brain, we examined the dynamic behavior of Xenopus RGC
      axons soon after they innervate the optic tectum. Time-lapse confocal microscopy
      imaging of RGC axons expressing enhanced yellow fluorescent protein demonstrated
      that netrin-1 is involved in early axon branching, as recombinant netrin-1 halted
      further advancement of growth cones into the tectum and induced back branching.
      RGC growth cones exhibited differential responses to netrin-1 that depended on
      the degree of differentiation of the axon and the developmental stage of the
      tadpole. Netrin-1 decreased the total number of branches on newly arrived RGC
      growth cones at the target, but increased the dynamic branching of more mature
      arbors at the later developmental stage. To further explore the response of
      axonal growth cones to netrin, Xenopus RGC axons were followed in culture by time
      lapse imaging. Exposure to netrin-1 rapidly increased the forward advancement of
      the axon and decreased the size and expanse of the growth cone, while also
      inducing back branching. Taken together, the differential in vivo and in vitro
      responses to netrin-1 suggest that netrin alone is not sufficient to induce the
      cessation of growth cone advancement in the absence of a target but can
      independently modulate axon branching. Collectively, our findings reveal a novel
      role for netrin on RGC axon branch initiation as growth cones innervate their
      target.

PMID- 21858930
TI  - Direct and vicarious violent victimization and juvenile delinquency: an
      application of general strain theory.
AB  - Using a national probability sample of adolescents (12-17), this study applies
      general strain theory to how violent victimization, vicarious violent
      victimization, and dual violent victimization affect juvenile violent/property
      crime and drug use. In addition, the mediating effect and moderating effect of
      depression, low social control, and delinquent peer association on the
      victimization-delinquency relationship is also examined. Based on SEM analyses
      and contingency tables, the results indicate that all three types of violent
      victimization have significant and positive direct effects on violent/property
      crime and drug use. In addition, the expected mediating effects and moderating
      effects are also found. Limitations and future directions are discussed.

PMID- 21858933
TI  - SAMHSA outlines strategic initiatives for 2011-2014.

PMID- 21858932
TI  - Joint physical custody and neighborhood friendships in middle childhood.
AB  - Almost half of first marriages end in divorce, which in turn may produce joint
      physical custody arrangements. Seen by many states to be in the best interest of
      the child, joint physical custody is increasingly common. Yet much is unknown
      about its consequences for children. This article considers how joint physical
      custody arrangements affect children's neighborhood friendships, an important
      component of child well-being because of their contributions to social and
      cognitive development. Thirteen parents and 17 children (aged 5-11) in 10
      families, selected via convenience and snowball sampling, participated in
      semistructured interviews. The findings suggest that joint physical custody
      arrangements do not imperil children's neighborhood friendships; indeed, most
      children and parents interviewed voiced contentment in this area.

PMID- 21858934
TI  - Outbreak news. West Nile virus infection in Europe.

PMID- 21858935
TI  - Narrow band imaging cystoscopy.

PMID- 21858936
TI  - The field of radiation in imaging.

PMID- 21858937
TI  - Chest X-ray quiz.

PMID- 21858938
TI  - Correction: Comparative effectiveness and safety of medications for type 2
      diabetes.

PMID- 21858939
TI  - Heading west: from nurse to truck driver.

PMID- 21858940
TI  - No jobs on graduation.

PMID- 21858941
TI  - Precarious employment in nursing.

PMID- 21858942
TI  - Article gives no clinical context.

PMID- 21858943
TI  - Viewing pulse oximetry with caution.

PMID- 21858944
TI  - Yew tree poisoning: a near-fatal lesson from history.

PMID- 21858945
TI  - How do I manage a patient with suspected acute pulmonary embolism?

PMID- 21858946
TI  - Outcome of referrals to a community palliative care service: where do patients
      die?

PMID- 21858947
TI  - Evidence-based policy in the new organizational paradigm part 1.

PMID- 21858948
TI  - Evaluation of fast-ELISA versus standard-ELISA to diagnose human fasciolosis.

PMID- 21858949
TI  - Stroke--for poorer not richer.

PMID- 21858950
TI  - [The research in health is profitable].

PMID- 21858951
TI  - The pain summit: moving the agenda forward.

PMID- 21858952
TI  - Dealing with Mr. COPD.

PMID- 21858953
TI  - Did you file a false report?

PMID- 21858954
TI  - Correlates of trading sex for methamphetamine in a sample of HIV-negative
      heterosexual methamphetamine users.
AB  - While many studies have examined correlates of trading sex for money, few have
      examined factors associated with exclusive trading of sex for drugs. We
      identified sociodemographic, behavioral, and psychological correlates of trading
      sex for methamphetamine in a sample of HIV-negative heterosexual men and women
      who were enrolled in a sexual risk reduction intervention in San Diego,
      California. Of 342 participants, 26% overall (21% of males and 31% of females)
      reported trading sex for methamphetamine in the past two months. Multiple
      logistic regression analysis revealed that recently trading sex for
      methamphetamine was independently associated with being female, homeless, binging
      on methamphetamine, sexual victimization in the past two months, engaging in anal
      sex 24 or more times in the past two months, and higher sexual compulsivity
      scores. Effective interventions for this high-risk population should consider
      gender-focused counseling for sexual abuse, motivational enhancement therapy,
      social-cognitive skills training, as well as enhanced access and utilization of
      social services, including drug treatment.

PMID- 21858955
TI  - Substance use and abuse among men using the Internet specifically to find
      partners for unprotected sex.
AB  - This study was based on a national random sample of 332 MSM who use the Internet
      to seek men with whom they can engage in unprotected sex. Data collection was
      conducted via telephone interviews between January 2008 and May 2009. Illegal
      drug use was highly prevalent in this population, particularly when compared to
      men in the general population: 85.2% of the men in the study versus 59.5% of men
      in the adult population reported lifetime use of an illegal drug, and 60.1% of
      the men in the study versus 9.9% of men in the adult population reported use of
      an illegal drug during the preceding 30 days. Substance abuse problems and drug
      dependence were also highly prevalent, with a sizable proportion of the men
      having unmet treatment needs. Most study participants (56.4%) reported a
      preference for having sex while under the influence of alcohol and/or other
      drugs, with the large majority of these persons (85.9%) expressing a preference
      for illegal drug use in that context. The author concludes that men who use the
      Internet to find partners for unprotected sex tend to have extensive drug use
      histories, and their experimentation with illegal drugs continues well into their
      40s, 50s, and beyond. A sizable proportion of these men need substance abuse
      education, prevention services, intervention services, and/or drug treatment.

PMID- 21858956
TI  - Redefining retention: recovery from the patient's perspective.
AB  - This study examines the process of discharge and treatment reentry for six
      participants who entered treatment voluntarily but were administratively
      discharged from methadone treatment programs. The participants completed
      semistructured interviews at treatment entry and at four, eight and 12 months
      post-treatment entry. Grounded theory methodology was used to examine the
      phenomenon of treatment reentry from the perspective of the patients, who often
      viewed their recovery as an accumulation of positive changes. Differences in
      terms of the patients' goals and motivations for seeking treatment from those of
      the treatment programs, combined with difficulties encountered during the
      treatment process eventually led to discharge. However, these patients were then
      able to navigate their way through the treatment system in different ways in
      order to remain in treatment. The authors conclude that failure to abide by
      treatment clinic rules do not necessary constitute "treatment failure" from the
      perspective of patients, who often wish to remain in treatment even if it is not
      progressing optimally from the program's perspective. As a result, the recovery
      process can be more fragmented and is often characterized by a series of cyclical
      treatment episodes rather than continuous time in treatment, thereby impeding
      their progress towards recovery.

PMID- 21858957
TI  - Neurogenetics and clinical evidence for the putative activation of the brain
      reward circuitry by a neuroadaptagen: proposing an addiction candidate gene panel
      map.
AB  - This document presents evidence supporting the role of the KB220/KB220Z
      neuroadaptagens consisting of amino-acid neurotransmitter precursors and
      enkephalinase-catecholamine-methyl-transferase (COMT) inhibition therapy called
      Neuroadaptagen Amino Acid Therapy (NAAT) in brain reward function. It is becoming
      increasingly clear that this novel formulation is the first neuroadaptagen known
      to activate the brain reward circuitry. Ongoing research repeatedly confirms the
      numerous clinical effects that ultimately result in significant benefits for
      victims having genetic antecedents for all addictive, compulsive and impulsive
      behaviors. These behaviors are correctly classified under the rubric of"Reward
      Deficiency Syndrome" (RDS). We are proposing a novel addiction candidate gene
      map. We present preliminary findings in the United States using qEGG and in China
      using Functional Magnetic Resonance Imaging (fMRI) regarding the effects of oral
      NAAT on the activation of brain reward circuitry in victims of SUD. In
      unpublished data utilizing an fMRI 2X2 design at resting state, NAAT in
      comparison to placebo shows activation of the caudate brain region and
      potentially a smoothing out of heroin-induced putamen (a site for emotionality)
      abnormal connectivity. Although awaiting final analysis, if confirmed by ongoing
      studies in China coupled with published qEEG results in America, showing an
      increase in alpha and low beta, NAAT may be shown to impact treatment outcomes.

PMID- 21858958
TI  - Who are medical marijuana patients? Population characteristics from nine
      California assessment clinics.
AB  - Marijuana is a currently illegal psychoactive drug that many physicians believe
      has substantial therapeutic uses. The medical literature contains a growing
      number of studies on cannabinoids as well as case studies and anecdotal reports
      suggesting therapeutic potential. Fifteen states have passed medical marijuana
      laws, but little is known about the growing population of patients who use
      marijuana medicinally. This article reports on a sample of 1,746 patients from a
      network of nine medical marijuana evaluation clinics in California. Patients
      completed a standardized medical history form; evaluating physicians completed
      standardized evaluation forms. From this data we describe patient
      characteristics, self-reported presenting symptoms, physician evaluations, other
      treatments tried, other drug use, and medical marijuana use practices. Pain,
      insomnia, and anxiety were the most common conditions for which evaluating
      physicians recommended medical marijuana. Shifts in the medical marijuana patient
      population over time, the need for further research, and the issue of diversion
      are discussed.

PMID- 21858959
TI  - Integrating buprenorphine treatment into a public healthcare system: the San
      Francisco Department of Public Health's office-based Buprenorphine Pilot Program.
AB  - Despite well-documented efficacy, US physicians have been relatively slow to
      embrace the use of buprenorphine for the treatment of opioid dependence. In order
      to introduce and support the use of buprenorphine across the San Francisco
      Department of Public Health system of care, the Buprenorphine Pilot Program was
      initiated in 2003. Program treatment sites included a centralized buprenorphine
      induction clinic and program pharmacy, and three community-based treatment sites;
      two primary care clinics and a private dual diagnosis group practice. The target
      patient population consisted of opioid-dependent patients typically seen in an
      urban, public health setting, including individuals experiencing extreme poverty,
      homelessness/unstable housing, unemployment, polysubstance abuse/dependence,
      coexisting mental health disorders, and/or little psychosocial support. This
      program evaluation reviews patient characteristics, treatment retention,
      substance use over time, patient impressions, and provider practices for the 57
      patients admitted between 9/1/03 and 8/31/05. At baseline, over 80% of patients
      were injecting heroin, over 40% were homeless, and over one-third were using
      cocaine. Outcomes included an overall one-year retention rate of 61%, a rapid and
      dramatic decline in opioid use, very positive patient impressions of the program
      and of buprenorphine, and significant shifts in provider practices over time.

PMID- 21858961
TI  - Psychedelic drugs, hippie counterculture, speed and phenobarbital treatment of
      sedative-hypnotic dependence: a journey to the Haight Ashbury in the Sixties.
AB  - The 1960s were a time of social upheaval, wars, vibrant creativity and missed
      opportunity. Mainstream culture and a psychedelic drug-using counterculture
      shared a belief in "better living through chemistry'," but they disagreed about
      the particular chemistry. The Vietnam war and the cold war with the Soviet Union,
      racial discrimination, and gender roles fueled political activism. "Yes we can"
      was not a slogan of the time but political activists clearly believed they could
      change the beliefs, attitudes and behavior of mainstream culture; and they did.
      Hippie counterculture on the other hand was largely alienated and strove
      primarily to develop a separate culture with its own mores, beliefs and
      lifestyles. Although there was some overlap between hippies and activists,
      hippies didn't generally have the same sense of political empowerment. Hippie
      enclaves developed in New York; Boston; Seattle; Austin, Texas and elsewhere; but
      the epicenter was arguably the Haight-Asbury District of San Francisco.
      Psychedelic drugs, marijuana and the Vietnam war were among many wedge issues.
      This paper conjures up a personal history related to the evolution of the hippie
      counterculture, changing drug use patterns in the Haight-Ashbury, and the origins
      of a technique of withdrawing patients from barbiturates and other sedative
      hypnotics using phenobarbital variously known as the "Phenobarbital Withdrawal
      Protocol, or the "Smith and Wesson Protocol."

PMID- 21858960
TI  - Attitudes and practices of hookah smokers in the San Francisco Bay Area.
AB  - As many as 10 million people will die annually by the year 2030 due to tobacco
      related causes. While much research has focused on cigarettes, the increasing
      popularity of smoking hookah (water pipe) has received much less attention.
      Epidemiological studies have been carried out in India, Pakistan, Syria, Kuwait,
      and Lebanon, but there are few in the United States. Hookah smoking is typically
      a social activity and there are many myths and rumors about the relative safety
      of smoking hookah compared to cigarettes. The aim of this study was to identify
      the knowledge, attitudes, and practices of hookah smokers in the San Francisco
      Bay Area. We sampled 50 participants (25 male and 25 female) who were mostly
      college students at the University of California, Berkeley. Hookah smoking was
      occasional among those sampled, with only six participants (12%) reporting weekly
      hookah smoking. The majority of respondents considered hookah smoking to be
      harmful to their health (88%), yet 52% had no intention of quitting. More
      definitive studies conveying the possible harm of hookah smoking are necessary to
      serve as a basis for health education programs and policy changes towards this
      potentially harmful activity.

PMID- 21858962
TI  - The world of the Haight-Ashbury speed freak.

PMID- 21858963
TI  - [Epidemic keratoconjunctivitis].
AB  - INTRODUCTION: Keratocnjunctivitis is corneal and conjunctival inflammation.
      Clinical signs involve the irritating trio: mixed hyperemia of conjunctival
      membranes, corneal subepthelial infiltrates and regional lymphadenopathy. The
      most common causes of epidemic are adenovirus, herpes virus, and rarely
      cytomegalovirus, which are now occurring with higher frequency as secondary
      infections. OBJECTIVE: The aim of the study was to present and analyze
      keratoconjunctival epidemics in the region of Kragujevac from September 2008 to
      February 2009, as well as to analyze clinical features related to virusological
      findings and etiology. METHODS: In 329 patients we performed clinical examination
      (biomicroscopy, fluorescent test, corneal sensitivity test), collecting standard
      specimen of the conjuctiva and cornea, made serological examination, and sent the
      specimens to the Virusology Institute "Torlak" in Belgrade for the confirmation
      of epidemic etiology. The patients were treated with local and symptomatological
      therapy. The epidemic was eradicated in cooperation with a regional referent
      institution. All outpatients activities were ceased, while hospital hygienic,
      sanitary, intra-, extra-hospital and therapeutic procedures were undertaken.
      RESULTS: The distribution of 329 patients by gender was equivalent. Most patients
      were aged from 27 to 34 years (25%) of working population. The distribution of
      patients by clinical features showed the predominance of follicular hyperplasy
      (93.62%). The distribution according to the time of the first symptoms onset
      showed the frequency of 50% of corneal infiltrate in the second week. The period
      elapsed from the diagnosis to cure was three weeks in 50% of patients.
      Serological tests confirmed the mixed distribution of the cause. CONCLUSION:
      Based on the authors' experience, in order to eradicate epidemics as fast as
      possible and achieve efficient treatment, it is recommended that the epidemic
      should be reported, guidelines of referent institutions be obeyed, all of which
      diminishes the recognizable professional risk and decreases mistakes.

PMID- 21858964
TI  - [The impact of hearing loss on the quality of life in adults].
AB  - INTRODUCTION: The hearing apparatus is one of the most important factors related
      to the development of oral communication. Thus, hearing disorders and deafness
      lead to severe handicap. Hearing impairment in adults cause verbal communication
      disorders that influence psychical, emotional and social functioning. Nowadays,
      there is a noticeable world tendency towards improving hard of hearing person's
      quality of life. OBJECTIVE: Objective was to assess the association between
      hearing impairment and health-related quality of life. METHODS: A hundred adults
      with billateral hearing impairment underwent hearing examination and answered the
      Hering Handicap Inventory for the Elderly-Screening (HHIE-S, Ventry and
      Weinstein), specific for hearing impairment. RESULTS: Almost half of all
      participants (44%) had a moderate hearing loss, and 36% had a mild loss.
      Infrequently, participants had a severe degree of hearing loss (13%) and deafness
      (7%). Self reported hearing handicap revealed significant emotional, social and
      situational dysfunctions (chi2 = 40.960; df = 1; p < 0.01). Severity of hearing
      loss was significantly correlated with hearing handicap (r = 0.212; p < 0.05).
      More often, participants revealed social and situational than emotional hearing
      handicap (Chi2 = 131.89; df = 100; p < 0.05). Only 12% of all participants
      habitually used hearing aids, and they observed a significantly better quality of
      life scores (chi2 = 6.23; df = 1; p < 0.05). CONCLUSION: Health-related quality
      of life must be estimated as a factor of great importance. Investigations should
      involve a more extansive population with hearing loss and a national programme
      should be started.

PMID- 21858965
TI  - Keratocystic odontogenic tumour: an experience in the Northeast of Brazil.
AB  - INTRODUCTION: Keratocystic odontogenic tumours raise particular interest, because
      of their high recurrence rate and association with nevoid basal cell carcinoma
      syndrome. OBJECTIVE: To analyze the clinical and histopathological features of
      all cases diagnosed as keratocystic odontogenic tumour in a Brazilian population.
      METHODS: A total of 64 keratocystic odontogenic tumours, arising in forty-six
      patients, were evaluated using the following parameters: association with nevoid
      basal cell carcinoma syndrome, gender, age at first diagnosis, race, anatomical
      location, symptoms, radiographic features, history of recurrence, association
      with teeth, and treatment. RESULTS: Keratocystic odontogenic tumours were more
      frequent among women than men (1:0.84). The mean patient age was 31.5 years (SD:
      +/- 16.6). Ten tumours (16.4%) involved the maxilla and 51 (83.6%) the mandible.
      Swelling (n = 12; 46.1%), followed by pain and swelling (n = 4; 15.3%), were most
      common clinical manifestations. A unilocular radiotransparency with well-defined
      margins was the main radiographic finding (n = 29; 87.8%). A significant
      association was observed between the multilocular radiographic pattern and
      recurrence (p < 0.05, Fisher's Test). Sixty-one (95.3%) tumours were treated by
      surgical enucleation followed by bone curettage, and the recurrence rate was 13%
      (n = 6). This study showed that the keratocystic odontogenic tumours relapsed
      within a mean period of 25-36 months. CONCLUSION: Despite the results of this
      study being similar to previous reports found in the literature, it provides an
      important insight about keratocystic odontogenic tumours in a Brazilian
      population.

PMID- 21858966
TI  - [Incidence of lip and palate clefts in children in Nis from 1990 to 2007].
AB  - INTRODUCTION: Cleft lip and palate is a complex congenital anomaly of the
      orofacial system in children. OBJECTIVE: The aim of this study was to determine
      the incidence of live-born children with cleft lip and/or palate compared to the
      total number of children born in the period from January 1, 1990 to December 31,
      2007. METHODS: Epidemiological investigation was based on the records of live
      born children at the Hospital of Gynaecology and Obstetrics of the Clinical
      Centre Nis. The study included 61,116 live-born children, i.e. 56,905 full-term
      babies. RESULTS: The total number of registered clefts during the investigation
      period was 43 (22 boys and 21 girls). The most frequent were the secondary palate
      clefts (44.2%); combined cleft were present in 34.9%, while primary palate clefts
      were reported in 20.9%. In respect to the season and order of birth, there was no
      statistically significant difference in the frequency of the primary, secondary
      and complete palate clefts. The age of mothers was not identified as a risk
      factor for the occurrence of cleft lip and palate. CONCLUSION: In the studied
      period, 43 children were born with the cleft lip and/or palate, equally in boys
      as in girls. The secondary palate clefts were most frequent. The season and order
      of birth had no statistical influence on the occurrence of this anomaly.

PMID- 21858967
TI  - [Integrated approach to prevention and control of cardiovascular diseases].
AB  - INTRODUCTION: From 1984 to 2004, the city of Novi Sad participated in the
      international MONICA (Multinational MONItoring of trends and determinants in
      CArdiovascular disease) project, as one of the 38 research centres form 21
      countries around the world and in CINDI (Countrywide Integrated Noncommunicable
      Disease Intervention Programme) programme. OBJECTIVE: Objective was to indicate
      the advantages of the integrated approach to prevention and control of the
      cardiovascular disease (CVD) over mono-programmes and still present curative
      approach. Additional objective was the assessment of the vulnerability from the
      leading risk factors of the population of Novi Sad, based on the results and
      experience gained in realization of international projects. METHODS: We analysed
      the results obtained in the countries where MONICA project and CINDI programme
      have been applied. The results of their application in Novi Sad are analysed (the
      trend of the prevalence of risk factors, the incidence of coronary and
      cerebrovascular events). RESULTS: The prevalence of risk factors (except
      smoking), the incidence of coronary and cerebrovascular events are significantly
      increasing and are in positive correlation with the values of the linear
      trend.The decrease was only recorded in 1987 (the implementation of the
      intervention programme). CONCLUSION: The review of results and experiences in
      international projects and programs, clearly indicate the advantage of an
      integrated approach to prevention and control of CVD in relation to monoprograme.
      The great vulnerability of the population of Novi Sad of the risk factors of CVD
      points out the necessity of their reductions by the principles of integrated
      programmes of prevention and control.

PMID- 21858968
TI  - [Abdominal aortic surgery and renal anomalies].
AB  - INTRODUCTION: Kidney anomalies present a challenge even for the most experienced
      vascular surgeon in the reconstruction of the aortoilliac segment. The most
      significant anomalies described in the surgery of the aortoilliac segment are a
      horse-shoe and ectopic kidney. OBJECTIVE: The aim of this retrospective study was
      to analyze experience on 40 patients with renal anomalies, who underwent surgery
      of the aortoilliac segment and to determine attitudes on conventional surgical
      treatment. METHODS: In the period from 1992 to 2009, at the Clinic for Vascular
      Surgery of the Clinical Centre of Belgrade we operated on 40 patients with renal
      anomalies and aortic disease (aneurysmatic and obstructive). The retrospective
      analysis involved standard epidemiological data of each patient (gender, age,
      risk factors for atherosclerosis, type of anomaly, type of aortic disease,
      presurgical parameter values of renal function), type of surgical approach
      (laparatomy or retroperitoneal approach), classification of the renal isthmus,
      reimplantation of renal arteries and perioperative morbidity and mortality.
      RESULTS: Twenty patients were males In 30 (70%) patients we diagnosed a horse
      shoe kidney and in 10(30%) ectopic kidney. In the cases of ruptured aneurysm of
      the abdominal aorta the diagnosis was made by ultrasound findings. Pre
      surgically, renal anomalies were confirmed in all patients, except in those with
      a ruptured aneurysm who underwent urgent surgery. In all patients we applied
      medial laparatomy, except in those with a thoracoabdominal aneurysm type IV, when
      the retroperitonal approach was necessary. On average the patients were under
      follow-up for 6.2 years (from 6 months to 17 years). CONCLUSION: Under our
      conditions, the so-called double clamp technique with the preservation of the
      kidney gave best results in the patients with renal anomalies and aortic disease.

PMID- 21858969
TI  - Change of bronchial hyperresponsiveness in asthmatic children.
AB  - INTRODUCTION: Bronchial hyperresponsiveness (BHR) is a factor in predicting
      bronchial asthma independently of inflammation markers. OBJECTIVE: The aims were
      to determine the frequency and important predictive facts of BHR and the effect
      of prophylaxis by Global Initiative for Asthma (GINA) and National Asthma
      Education and Prevention Program (NAEPP) on BHR in asthmatic children. METHODS:
      BHR in 106 children was evaluated by the bronchoprovocation test with
      methacholine. RESULTS: The prevalence rate of symptomatic BHR is 18% for crucial
      point of PC20 = 4.1 +/- 3.03 mg/ml and PD20 = 3.22 +/- 2.59 micromol
      methacholine. On average asthmatic children express moderate BHR, which persists
      even two years after administering prophylaxis. After two years bronchial
      reactivity is significantly smaller, the change of FEV1 is significantly smaller,
      the velocity of change of slope dose response curve (sDRC) is faster and the
      provocative concentration of methacholine that causes wheezing is 2-3 times
      lower. A mild sDRC shows milder bronchoconstriction after two years. The fast
      change of bronchial reactivity in 41% of asthmatic children is contributed to
      aero-pollution with sulfur dioxide and/or, possible insufficient and/or
      inadequate treatment during two years of administering prophylaxis. A
      simultaneous effect of allergens from home environment and grass and tree pollens
      and of excessive aero-pollution on children's airways is important in the onset
      of symptomatic BHR. After two years of treatment by GINA and NAEPP children do
      not show asthma symptoms or show mild asthma symptoms, however bronchial
      sensitivity remains unchanged. CONCLUSION: Optimal duration of anti-inflammatory
      treatment in asthmatic children who show moderate bronchial hyperresponsiveness
      should be longer than two years.

PMID- 21858970
TI  - [Obesity and chronic obstructive pulmonary disease].
AB  - INTRODUCTION: Nutritional abnormalities have one of the most important systematic
      effects on chronic obstructive pulmonary disease (COPD). A relationship between
      COPD and obesity has been observed and recognised. In COPD patients, beside
      changes in the total body weight, changes in body composition are also possible
      with the loss of fat-free mass (FFM). OBJECTIVE: This study was undertaken to
      evaluate the impact of obesity and the change of body composition on the
      pulmonary function, dyspnoea level and the quality of life in COPD patients.
      METHODS: Seventy-nine patients in the stable state of COPD were evaluated.
      Pulmonary function and arterial blood gas analysis were assessed. Nutritional
      status was analyzed according to Body Mass Index (BMI). Body composition was
      evaluated by using anthropometric measurement by fat free mass index (FFMI).
      Quality of life was assessed using the St. George Respiratory Questionnaire
      (SGRQ). The Visual Analogue Scale (VAS) was used to evaluate dyspnoea. RESULTS:
      The highest prevalence of obesity (50.0%) was found in patients with mild COPD,
      while the lowest prevalence was detected in very severe COPD patients (10.0%).
      The loss of FFM occurred in 22.2% patients with normal body weight and in 9.0% of
      overweight COPD patients.The quality of life was lower in obese patients compared
      to other COPD patients. A higher dyspnoea level was also present in obese
      patients. The lowest airflow obstruction was in obese patients (p = 0.023). We
      found a significant positive correlation between forced expiratory volume in the
      first second (FEV1%) and BMI (r = 0.326, p = 0.003), FEV1% and FFMI (r = 0.321, p
      = 0.004). CONCLUSION: The highest prevalence of obesity was in patients with mild
      COPD. Obese patients with COPD had the lowest level of airflow obstruction,
      higher dyspnoea level and lower quality of life in comparison to other COPD
      patients.

PMID- 21858971
TI  - Does sclerotherapy of remnant little oesophageal varices after endoscopic
      ligation have impact on the reduction of recurrent varices? Prospective study.
AB  - INTRODUCTION: Endoscopic band ligation (EBL) is superior to endoscopic injection
      sclerotherapy (EIS) of oesophageal varices, however, EBL is associated with a
      higher rate of variceal recurrences. OBJECTIVE: To examine whether the reduction
      of recurrent varices can be achieved by additional sclerotherapy of remnant
      little varices after ligation. METHODS: Forty-eight patients with liver cirrhosis
      who had previously bled from oesophageal varices were examined. Endoscopic
      therapy was performed in order to prevent recurrent variceal bleeding. I group:
      in 23 patients ligation of oesophageal varices with multi band ligation device
      was applied (EBL group). II group: in 25 patients sclerotherapy using polydocanol
      or absolute alcohol was applied after reducing the size of varices using ligation
      (EBL and EIS group). RESULTS: There was no statistically significant difference
      between the examined groups of patients in relation to the number of sessions for
      variceal eradication, recurrence of variceal bleeding, deterioration of portal
      gastropathy and mortality in the observed period from 18.8 +/- 18.6 months (EBL
      group) and 22.2 +/- 26.2 months (EBL and EIS group). Variceal recurrence was
      verified in 21.7% of patients of the EBL group and 16% of the EBL and EIS group,
      but the difference was not statistically important. Several complications, such
      as dysphagia and chest pain, were statistically more frequent in the EBL and EIS
      group of patients. CONCLUSION: The combined method of ligation and extra
      sclerosing of remnant small oesophageal varices after ligation does not have
      advantage in relation to the ligation alone.

PMID- 21858972
TI  - Intraoperative air testing of colorectal anastomoses.
AB  - INTRODUCTION: Intraoperative anastomotic air testing of stapled colorectal
      anastomosis is performed by filling the pelvis with saline solution and
      insufflating the rectum with air through a sigmoidoscope. The presence of air
      bubbles indicates anastomotic leaks which are resolved during surgery. OBJECTIVE:
      The aim of this prospective, randomized study was to perform a comparative
      analysis regarding the number of anastomotic dehiscences in patients checked by
      air leak testing and in the control group without air testing. METHODS: After
      stapled colorectal anastomosis was performed, patients were randomized into two
      groups of 30 patients. The first group patients underwent intraoperative
      anastomotic air testing, whereas in the control group this procedure was not
      performed. The two groups were matched for age, sex, diagnosis and surgical
      procedure. RESULTS: Intraoperative air tests were positive in seven cases and
      anastomotic defects were repaired. After surgery, there were three clinical leaks
      in this group of patients. In the control group, there were six leaks (Unilateral
      Fischer's exact test, p = 0.24). The incidence of colorectal anastomotic
      dehiscences in the study group was lower than in the control group by 50%.
      However, this finding was not statistically significant in our sample.
      CONCLUSION: In our opinion, intraoperative air testing of colorectal anastomosis
      is a good method for prevention of anastomotic dehiscence.

PMID- 21858973
TI  - [The role of hormonal ovarian ablation in adjuvant treatment of premenopausal
      breast cancer].
AB  - INTRODUCTION: Breast cancer is the most frequent malignant disease in women with
      about 25% compared to all malignant tumours. Chemotherapy, antiestrogen and
      ovarian ablation/ supression present effective adjuvant approach for
      premenopausal women diagnosed with hormonal depended, operable breast cancer.
      OBJECTIVE: To evaluate benefits of combined chemo/hormonal therapy that is
      undutiful, but optimal application has not yet been clearly determined. METHODS:
      Thirty-six women were divided into three therapy groups. The first group (13
      women) was treated with six cycles of adjuvant FAC chemotherapy followed by
      regular check-ups; the second group (13 women) after six cycles of adjuvant FAC
      chemotherapy continued treatment with a two-year application of goserelin given
      by subcutaneous injections (FAC-Z); the third group (10 women), after six cycles
      of adjuvant FAC chemotherapy continued with once per month application of
      gorselin for two years and a daily application of 20 mg tamoxifen for five years
      (FAC-Z-T). The length of overall disease free period and survival were analyzed
      in all three groups. RESULTS: The benefit of LH-RH analogues in premenopausal
      women with hormone-dependent breast cancer was found to be low, and probably
      limited to smaller subgroups of patients, possibly such as those with either both
      steroid receptors positive (ER and PR) or those with an extremely high level of
      steroid receptors. In our paper, analyses of such subgroups could not been
      performed due to a small sample of patients. The effect of therapy is better in
      patients, who developed amenorrhoea, regardless of the type of later hormonal
      therapy. CONCLUSION: Ovarial ablation, whatever the method, should be probably
      applied as early as possible within the treatment of early breast cancer,
      especially in patients in whom chemotherapy induced amenorrhoea is not expected,
      i.e. in very young female patients.

PMID- 21858974
TI  - Favourable prognostic factors in therapy related acute myeloid leukaemia.
AB  - INTRODUCTION: Therapy related acute myeloid leukaemia (t-AML) is a distinct
      clinical entity recognized by the World Health Organization classification
      occurring after chemotherapy and/or radiation treatment administered for a
      previous disease. T-AML is characterised by pancytopenia, three-lineage
      myelodysplasia, high frequency of unfavourable cytogenetics and short survival.
      OBJECTIVE: The aim of this study was to analyse clinical, cytogenetic, and
      cytological characteristics of t-AML and their impact on survival. METHODS:
      Seventeen patients with t-AML (8 male and 9 female; median age 59 years) were
      identified among 730 consecutive patients with acute myeloid leukaemia. The
      degree of three-lineage dysplasia as well as haematological, cytological and
      cytogenetic analyses, were assessed by standard methods. RESULTS: The patients
      survived a median of 62.5 days with the 10% probability of survival during two
      years. Prognostically favourable factors were a higher percentage of dysplastic
      granulocytic cells, age less than 60 years, and presence of prognostically
      favourable karyotype inv(16), t(15;17), t(8;21). CONCLUSION: The stated
      prognostic factors that include age, cytogenetics findings and granulocytic
      dysplasia analysis could contribute to adequate risk stratification of t-AML,
      though fuller results would require additional analyses.

PMID- 21858975
TI  - Pornography use and closeness with others in women.
AB  - INTRODUCTION: Closeness/intimacy and pornography are sometimes linked and
      frequently presented as competing with each other. They have been the subject of
      some research but many issues in the area remain controversial and indeterminate.
      OBJECTIVE: The aim of this pilot study was to establish whether female
      pornography users and non-users' ratings in terms of socio-emotional closeness
      differed, i.e. to examine the association between pornography use and aspects of
      socio-emotional closeness in a non-clinical sample of females. METHODS: Sixty-six
      females participated in the study. Their actual and ideal socioemotional
      closeness was measured by the Perceived Interpersonal Closeness Scale/PICS, while
      their pornography use was examined by the Background and Pornography Use
      Information Questionnaire. Potential links between the two variables and
      comparisons with the relevant results obtained by males are presented. RESULTS:
      The results showed that there were no significant differences between self
      reported female pornography users and non-users in terms of total closeness
      numbers and scores and also in specific socioemotional closeness with the most
      significant adults in their lives (i.e., partners, closest friends, mothers and
      fathers). CONCLUSION: The results confirmed that there were differences between
      females and males' approaches to pornography and closeness; females had lower
      interest in pornography and their use of it had not been associated with higher
      total closeness numbers and scores. Due to the participant group's size (N)
      limitations, this sample was rather used for preliminary investigations that
      would enable some elementary insight into females' relevant behaviours. Further
      investigations of pornography's complex links with socio-emotional and sexual
      closeness on larger samples may allow more reliable comparisons between gender
      and pornography users groups.

PMID- 21858976
TI  - [Influence of demographic and socioeconomic characteristics on the quality of
      life].
AB  - INTRODUCTION: The quality of life is a multidimensional concept, which is best
      expressed by the subjective well-being. Evaluation of the quality of life is the
      basis for measuring the well-being, and the determination of factors that
      determine the quality of life quality is the basis for its improvement.
      OBJECTIVE: To evaluate and assess the determinants of the perceived quality of
      life of group distinguishing features which characterize demographic and
      socioeconomic factors. METHODS: This was a cross-sectional study of a
      representative sample of the population in Serbia aged over 20 years (9479
      examinees). The quality of life was expressed by the perception of well-being
      (pleasure of life). Data on the examinees (demographic and socioeconomic
      characteristics) were collected by using a questionnaire for adults of each
      household. To process, analyze and present the data, we used the methods of
      parametric descriptive statistics (mean value, standard deviation, coefficient of
      variation), variance analysis and factor analysis. RESULTS: Although men
      evaluated the quality of life with a slightly higher grading, there was no
      statistically significant difference in the evaluation of the quality of life in
      relation to the examinee's gender (p > 0.005). Among the examinees there was a
      high statistically significant difference in grading the quality of life
      depending on age, level of education, marital status and type of job (p < 0.001).
      In relation to the number of children, there was no statistically significant
      difference in he grading of the quality of life (p > 0.005). CONCLUSION: The
      quality of life is influenced by numerous factors that characterize each person
      (demographic and socioeconomic characteristics of individual). Determining
      factors of the quality of life are numerous and diverse, and the manner and the
      strength of their influence are variable.

PMID- 21858977
TI  - [Macroglossia and Beckwith-Wiedemann syndrome].
AB  - INTRODUCTION: In 1963 Beckwith presented a report on the first patient with
      extreme cytomegaly of adrenal cortex, hyperplasia of kidneys and pancreas and
      Leydig cell hyperplasia. Wiedemann completed description of the new syndrome by
      adding umbilical hernia and macroglossia. The diagnosis is made based on the
      clinical signs of omphalocele or some other umbilical deformity, macroglossia,
      congenital asymmetry, visceromegaly (liver, pancreas, and kidneys). CASE OUTLINE:
      A 16-month-old male child was admitted for examination because of macroglossia.
      He underwent examination on several occasions by an endocrinologist due to
      recurrent hypoglycaemic crisis. The patient was observed by a paediatric
      neurophysicatrist for disorders of mental development. Hypoglycaemia, muscular
      hypotonia of the anterior abdominal wall with umbilical hernia and macroglossia
      were observed by clinical examination. Inratraoral examination revealed
      macroglossia with microstomia, suckling and swallowing difficulties, hypotonia of
      the perioral muscles with increased salivation. It was therefore decided to
      perform surgical reduction of the prominent tongue and develop good condition for
      nutrition, speech function and the development of orofacial system. CONCLUSION:
      The diagnosis of macroglossia is based on subjective clinical criteria such as
      the morphology and amount of protrusion of the tongue, difficulty in articulating
      sounds, breathing, and hypersalivation. Some authors have suggested that the
      tongue size may be analyzed radiographically with a cephalogram. Treatment of
      macroglossia is controversial because of the absence of objective clinical
      criteria.

PMID- 21858978
TI  - [External fixation in the treatment of shooting proximal humeral fracture with
      bone defect: a case report].
AB  - INTRODUCTION: Shooting injuries of shoulder with destruction of proximal humerus
      are rare and severe orthopaedic injuries. CASE OUTLINE: A 74-year-old patient was
      wounded at close range by a shotgun. He was wounded in the left shoulder and
      suffered a massive defect of the proximal humerus and soft tissue. The
      neurocirculatory finding of the injury extremity was normal. After a short
      resuscitation, x-ray of the thorax and the left shoulder registered a complete
      destruction of humeral head. After the primary treatment of the wound under
      general endotracheal anesthesia, the shoulder was stabilized with an external
      fixator type Mitkovic, with convergent orientation of the pins, where two pins
      were placed in the neck of scapula and two in the humeral shaft, because the left
      scapular acromion was fractured by shotgun projectiles. CONCLUSION: After radical
      wound debridement, external fixation is the method of choice for shoulder
      stabilisation in shooting injury of shoulder with bone defect. If this is not
      possible, pins of the left external skeletal fixator should be placed into the
      coracoid process and acromion. The pins can be also placed into the humeral
      shaft, as done in the presented case, and by which a good stability of the
      injured proximal humerus, easy approach to the wound for bandaging and
      reconstructive surgery can be achieved.

PMID- 21858979
TI  - [The importance of echocardiography in diagnostics of idiopathic pulmonary
      arterial hypertension: a case report].
AB  - INTRODUCTION: Idiopathic pulmonary arterial hypertension (IPAH) is rare and
      difficult progressive disease with prevalence of approximately 15 cases per
      million residents, with predominant female cases. CASE OUTLINE: A 47-year-old
      female presented with symptoms and signs of the right heart chambers failure.
      Over prior seven years the patient had the feeling of suffocation and fatigue
      when walking, and received treatment for bronchial asthma. Physical examination
      revealed a marked loud second heart sound over the pulmonary artery.
      Electrocardiogram: right ventricular hypertrophy. Spirometric (pulmonary
      capacity) test, cardiac perfusion scan and spiral CT scanning excluded secondary
      pulmonary arterial hypertension. Blood testing for connective tissue diseases and
      HIV were within normal reference limits. Transthoracic colour Doppler
      echocardiography demonstrated a mild tricuspid regurgitation with high values of
      estimated maximal and middle systolic pressure of the right ventricle (135/110 mm
      Hg), and excluded previous heart disease. Cardiac catheterization confirmed IPAH
      diagnosis, with systolic right ventricular pressure of 101/47/66 mm Hg and
      pulmonary capillary pressure of 30/13/10 mm Hg. Basic therapy with sildenafil,
      nevertheless, considerable limitations of strain tolerance was still present.
      CONCLUSION: IPAH is a severe heart disease with non-specific signs and symptoms.
      Screening for IPAH is transthoracic colour Doppler echocardiography shows high
      correlation with cardiac catheterization.

PMID- 21858980
TI  - [Intramural haematoma and penetrating aortic ulcer--outcome and treatment
      modalities: report of four cases].
AB  - INTRODUCTION: Intramural haematoma (IMH) and penetrating aortic ulcers (PAU) are
      the frequent cause of acute aortic syndrome that is disclosed with a rising
      frequency due to the development of new diagnostic methods. Different symptoms
      contribute to clinical misdiagnosis, while changeable locations and unpersuasive
      diameter can lead the radiologists to underestimate such changes. The outcome of
      PAU and IMH differs, and for the time being there are no data on prognostic
      factors. The diversity of symptoms and disease course is presented in four cases
      with different manifestations, treatment and outcome. OUTLINE OF CASES: Two
      patients with IMH were treated conservatively due to the process extensiveness
      and its morphology. One patient had a complete restitution, while the other had
      progression of the disease. Other two patients with PAU were treated by surgery
      (stent graft implantation) according to the morphology and diameter of the aorta.
      CONCLUSION: IMH and PAU should be suspected in patients with unclear clinical
      presentation (back and abdominal pains). Although outcome and complications of
      these diseases are well known, their incidence has not been fully studied.
      Endovascular treatment is less invasive and followed by a potentially lower rate
      of complications. However, usage of this method is justifiable only in patients
      with associated complications.

PMID- 21858981
TI  - Association of hereditary elliptocytosis and Gilbert's syndrome as the cause of
      biliary calculosis: case report.
AB  - INTRODUCTION: Biliary calculosis is rare in children. It occurs associated with
      different haemolytic and non-haemolytic disorders, which are sometimes also
      combined. CASE OUTLINE: A 15-year-old male was hospitalized due to biliary
      calculosis and non-conjugated hyperbilirubinemia. A mild non-conjugated
      hyperbilirubinemia, without anaemia and other symptoms of liver dysfunction, was
      registered at age 8 years, and 7 years later cholelithiasis with transitory
      choledocholithiasis. The finding of ellyptocytes in blood smear, which was also
      verified in mother, normal haemoglobin count and the absence of diseases followed
      by secondary dysmorphic erythrocytes of this type, indicated a clinically milder
      (compensated) hereditary ellyptocytosis, while more than a double increase of non
      conjugated serum bilirubin fracture after a three-day hypocaloric diet (400 kcal
      per day) showed the concurrent presence of Gilbert's syndrome. In the
      laparascopically removed gallbladder a larger number of small pigmented calculi
      were disclosed. CONCLUSION: Gilbert's syndrome is an essential precipitating
      factor of biliary calculosis in patients with chronic haemolytic condition. Thus,
      in all cases of biliary calculosis and non-conjugated hyperbilirubinemia with
      absent clinical and laboratory parameters of liver disorders and anaemia, except
      in compensated haemolytic disease and Gilbert's syndrome as isolated disorders, a
      possibility of their association should be taken into consideration.

PMID- 21858982
TI  - [Giant haemorrhagic (pseudo)cyst of the pancreas of unknown aetiology].
AB  - INTRODUCTION: Cystic lesions of the pancreas are frequent. Most frequently their
      aetiology can be easily established. It is very rare that the nature and
      aetiology of these lesions cannot be reliably established. CASE OUTLINE: A 40
      year-old male without trauma, alcohol abuse, acute or chronic pancreatitis in
      illness history was successfully operated on for a haemorrhagic (pseudo)cyst of
      the back wall of the pancreas tail containing 4.5 litres of haemorrhagic content.
      The cyst did not contain either epithelium or tumour stroma, and the pancreas did
      not show any changes of acute or chronic pancreatitis. Hystology did not show
      signs of angiectatic pseudocyst. CONCLUSION: In spite of all efforts, the authors
      could not establish the real nature of the (pseudo)cyst of the pancreas or find a
      similar case described in the literature. Nevertheless, the authors believe that
      it was probably an angiectatic cyst.

PMID- 21858983
TI  - [Sudden cardiac death in young athletes].
AB  - Cardiovascular diseases are the cause of death in up to 90% of athletes. The most
      frequent cause of death in young athletes is a sudden cardiac death (SCD). Causes
      of SCD among athletes are strongly correlated with age. In young athletes (< 35
      years), the leading causes are congenital cardiac diseases, particularly
      hypertrophic cardiomyopathy and congenital coronary artery anomalies. By
      contrast, most of deaths in older athletes (< 35 years) are due to coronary
      artery disease. Although there is no possibility to decrease the risk of SCD to
      "zero", especially in sport competitions, clear recommendations, if available,
      for cardiovascular evaluation before athletic participation and side effects of
      sports activities, would minimize the frequency of SCD. If a specific condition
      of the cardiovascular system is diagnosed, it is necessary to establish the risk
      of SCD associated with a continual involvement in physical activities and
      competitive sports, and to define clearly disqualification criteria for each
      individual athlete.

PMID- 21858984
TI  - [Current knowledge of bacterial vaginosis].
AB  - Bacterial vaginosis, earlier termed nonspecific vaginitis (anaerobic vaginosis)
      because of the absence of recognized pathogens, is most common vaginal syndrome
      of women of childbearing age affecting 15-30%. This syndrome, whose aetiology and
      pathogenesis remains unknown, is characterized by significant changes in the
      vaginal ecosystem. These changes consist of a decrease in the number of
      lactobacilli and a large increase in the number of anaerobic organisms. The
      bacteria adhere to desquamated epithelial cells with a distinctive appearance of
      clue cells The main complaints of women with symptomatic bacterial vaginosis
      include vaginal discharge and odour. However, a significant number of all women
      who have bacterial vaginosis deny symptoms. Bacterial vaginosis is associated
      with a number of gynaecologic and obstetric complications including cervicitis,
      cervical neoplasia, pelvic inflammatory disease, postoperative infections, and
      preterm labour.The diagnosis is most frequently made based on vaginal smear
      stained according to Gram (Nugent scoring method). Metronidazole and clindamycin
      are the drugs of choice for treatment of women with bacterial vaginosis. Which
      women should undergo treatment? According to the prevailing attitude, it should
      include women with symptoms. Symptomatic women with frequent relapses of
      bacterial vaginosisas, as a rule, have poor response to the applied therapy. To
      achieve better efficiency in the treatment of such women, it is necessary to have
      more extensive understanding of all factors in the pathogenesis of the syndrome.

PMID- 21858985
TI  - [Creative work of Greene Vardiman Black].
AB  - Over hundred years has elapsed since the publication of "Operative Dentistry"
      (1908), a book by the famous odontologist and scientist Greene Vardiman Black.
      Throughout all his life Black worked hard on education, research, lecturing,
      publishing and teaching others. The innovator in many fields of dental medicine,
      particularly conservative therapy, he patented numerous inventions, implemented
      the standardization of instruments and procedures, constructed stomatological
      drills, gnathodynamometer, material hardness testing moulds, micrometer and
      microtome. Black is the author of more than 500 articles and innovations, as well
      as several exceptional books that are considered as classic within the domain of
      the dental literature, and which many generations were educated on. One can
      certainly say that Black occupies the honorary position among the eminent
      personalities of dental scientist as one of the founders of contemporary
      stomatology. If we take into consideration Black as to his merits in operative
      dentistry and wider, it could be confirmed that the epoch of contemporary
      dentistry could be divided into the era before Black, when many dental procedures
      were performed without scientific foundation, the time during Black when many
      dilemmas were resolved in operative dentistry branches backed up by laboratory
      investigations, and finally the homage period of the 20th century when the
      application of his postulates, instruments and conclusions were gradually being
      abandoned giving way to modern doctrines and materials due to the rapid
      advancement of industry of dental materials and operative techniques in modern
      stomatology all of which should be credited to the development of basic sciences.

PMID- 21858986
TI  - Point/counterpoint. High intensity focused ultrasound may be superior to
      radiation therapy for the treatment of early stage prostate cancer.

PMID- 21858987
TI  - Technical note: Extension of Van Herk's treatment margin model for anisotropic
      systematic positioning errors in cartesian coordinate systema.
AB  - PURPOSE: A coefficient of a treatment margin model for anisotropic systematic
      positioning errors has been calculated in Cartesian coordinate system based on
      van Herk's analytical formulation. METHODS: Three-dimensional (3D) patient
      population distribution was formulated in Cartesian coordinate system to model
      anisotropic systematic positioning errors. Analytical 3D integration with
      anisotropic standard deviations Sigma's and the following Newton's method yielded
      the coefficient of van Herk's systematic positioning error model in Cartesian
      coordinate system. RESULTS: The treatment margins for the anisotropic systematic
      errors in Cartesian coordinate system were 2.1 Sigma for 90% patient population
      coverage and 2.4 Sigma for 95% patient population coverage. CONCLUSIONS: It was
      found that the treatment margins for anisotropic systematic positioning errors in
      Cartesian coordinate system were smaller than those for the isotropic model in
      spherical coordinate system for a given patient population coverage probability.

PMID- 21858988
TI  - Image filtering as an alternative to the application of a different
      reconstruction kernel in CT imaging: feasibility study in lung cancer screening.
AB  - PURPOSE: While the acquisition of projection data in a computed tomography (CT)
      scanner is generally cqrried out once, the projection data is often removed from
      the system, making further reconstruction with a different reconstruction filter
      impossible. The reconstruction kernel is one of the most important parameters. To
      have access to all the reconstructions, either prior reconstructions with
      multiple kernels must be performed or the projection data must be stored. Each of
      these requirements would increase the burden on data archiving. This study aimed
      to design an effective method to achieve similar image quality using an image
      filtering technique in the image space, instead of a reconstruction filter in the
      projection space for CT imaging. The authors evaluated the clinical feasibility
      of the proposed method in lung cancer screening. METHODS: The proposed technique
      is essentially the same as common image filtering, which performs processing in
      the spatial-frequency domain with a filter function. However, the filter function
      was determined based on the quantitative analysis of the point spread functions
      (PSFs) measured in the system. The modulation transfer functions (MTFs) were
      derived from the PSFs, and the ratio of the MTFs was used as the filter function.
      Therefore, using an image reconstructed with a kernel, an image reconstructed
      with a different kernel was obtained by filtering, which used the ratio of the
      MTFs obtained for the two kernels. The performance of the method was evaluated by
      using routine clinical images obtained from CT screening for lung cancer in five
      subjects. RESULTS: Filtered images for all combinations of three types of
      reconstruction kernels ("smooth," "standard," and "sharp" kernels) showed good
      agreement with original reconstructed images regarded as the gold standard. On
      the filtered images, abnormal shadows suspected as being lung cancers were
      identical to those on the reconstructed images. The standard deviations (SDs) for
      the difference between filtered images and reconstructed images ranged from 1.9
      to 23.5 Hounsfield units for all kernel combinations; these SDs were much smaller
      than the noise SDs in the reconstructed images. CONCLUSIONS: The proposed method
      has good performance and is clinically feasible in lung cancer screening. This
      method can be applied to images reconstructed on any scanner by measuring the
      PSFs in each system.

PMID- 21858989
TI  - Experimental investigation of a moving averaging algorithm for motion
      perpendicular to the leaf travel direction in dynamic MLC target tracking.
AB  - PURPOSE: In dynamic multileaf collimator (MLC) motion tracking with complex
      intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular
      to the MLC leaf travel direction can cause beam holds, which increase beam
      delivery time by up to a factor of 4. As a means to balance delivery efficiency
      and accuracy, a moving average algorithm was incorporated into a dynamic MLC
      motion tracking system (i.e., moving average tracking) to account for target
      motion perpendicular to the MLC leaf travel direction. The experimental
      investigation of the moving average algorithm compared with real-time tracking
      and no compensation beam delivery is described. METHODS: The properties of the
      moving average algorithm were measured and compared with those of real-time
      tracking (dynamic MLC motion tracking accounting for both target motion parallel
      and perpendicular to the leaf travel direction) and no compensation beam
      delivery. The algorithm was investigated using a synthetic motion trace with a
      baseline drift and four patient-measured 3D tumor motion traces representing
      regular and irregular motions with varying baseline drifts. Each motion trace was
      reproduced by a moving platform. The delivery efficiency, geometric accuracy, and
      dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and
      dynamic sliding window IMRT treatment plans using the synthetic and patient
      motion traces. The dosimetric accuracy was quantified via a tgamma-test with a
      3%/3 mm criterion. RESULTS: The delivery efficiency ranged from 89 to 100% for
      moving average tracking, 26%-100% for real-time tracking, and 100% (by
      definition) for no compensation. The root-mean-square geometric error ranged from
      3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and
      3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the
      gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time
      tracking, and 10%-47% for no compensation. CONCLUSIONS: The delivery efficiency
      of moving average tracking was up to four times higher than that of real-time
      tracking and approached the efficiency of no compensation for all cases. The
      geometric accuracy and dosimetric accuracy of the moving average algorithm was
      between real-time tracking and no compensation, approximately half the percentage
      of dosimetric points failing the gamma-test compared with no compensation.

PMID- 21858990
TI  - Magnetic cell delivery for peripheral arterial disease: A theoretical framework.
AB  - PURPOSE: Our aim was to compare different magnet arrangements for magnetic cell
      delivery to human lower leg arteries and investigate the theoretical targeting
      efficiency under realistic flow conditions as a possible treatment after
      angioplasty. Additionally the potential of scaling down or translating the
      magnetic actuation device for preclinical studies was explored. METHODS: Using
      finite element methods, the magnetic field distribution was calculated in 3D for
      the optimization of magnet arrangements. Computational fluid dynamics simulations
      were performed for the human posterior tibial artery with the geometry and
      boundary condition data derived from magnetic resonance imaging (MRI) studies.
      These simulations were used to trace the trajectories of cells for an optimized
      magnet arrangement. Additionally the behavior of cells close to the vessel wall
      was investigated using a fluid-structure interaction model. RESULTS: The optimal
      magnet for the lower leg arteries was a Halbach cylinder k3 variety (12 elements
      with 900 rotation steps for the magnetization orientation). With this magnet,
      numerical simulations predict a targeting efficiency of 6.25% could be achieved
      in the posterior tibial artery for cells containing 150 pg iron. Similar
      simulations, which were scaled down to rabbit dimensions while keeping the forces
      acting on a cell constant, lead to similar predicted targeting efficiencies.
      Fluid dynamic and fluid-structure interaction simulations predict that
      magnetically labeled cells within a 0.5% radii distance to the vessel wall would
      be attracted and remain at the wall under physiological flow conditions.
      CONCLUSIONS: First pass capture of magnetically labeled cells under pulsatile
      flow conditions in human lower leg arteries leads to low targeting efficiencies.
      However, this can be increased to almost 100% by stopping the blood flow for 5
      min. A magnetic actuation device can be designed for animal models that generate
      magnetic forces achievable for cells in human leg arteries.

PMID- 21858991
TI  - Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo
      code for dosimetry in nuclear medicine therapy.
AB  - PURPOSE: The calculation of patient-specific dose distribution can be achieved by
      Monte Carlo simulations or by analytical methods. In this study, FLUKA Monte
      Carlo code has been considered for use in nuclear medicine dosimetry. Up to now,
      FLUKA has mainly been dedicated to other fields, namely high energy physics,
      radiation protection, and hadrontherapy. When first employing a Monte Carlo code
      for nuclear medicine dosimetry, its results concerning electron transport at
      energies typical of nuclear medicine applications need to be verified. This is
      commonly achieved by means of calculation of a representative parameter and
      comparison with reference data. Dose point kernel (DPK), quantifying the energy
      deposition all around a point isotropic source, is often the one. METHODS: FLUKA
      DPKS have been calculated in both water and compact bone for monoenergetic
      electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy
      (89Sr, 90Y, 131I 153Sm, 177Lu, 186Re, and 188Re). Point isotropic sources have
      been simulated at the center of a water (bone) sphere, and deposed energy has
      been tallied in concentric shells. FLUKA outcomes have been compared to PENELOPE
      v.2008 results, calculated in this study as well. Moreover, in case of
      monoenergetic electrons in water, comparison with the data from the literature
      (ETRAN, GEANT4, MCNPX) has been done. Maximum percentage differences within
      0.8.RCSDA and 0.9.RCSDA for monoenergetic electrons (RCSDA being the continuous
      slowing down approximation range) and within 0.8.X90 and 0.9.X90 for isotopes
      (X90 being the radius of the sphere in which 90% of the emitted energy is
      absorbed) have been computed, together with the average percentage difference
      within 0.9.RCSDA and 0.9.X90 for electrons and isotopes, respectively. RESULTS:
      Concerning monoenergetic electrons, within 0.8.RCSDA (where 90%-97% of the
      particle energy is deposed), FLUKA and PENELOPE agree mostly within 7%, except
      for 10 and 20 keV electrons (12% in water, 8.3% in bone). The discrepancies
      between FLUKA and the other codes are of the same order of magnitude than those
      observed when comparing the other codes among them, which can be referred to the
      different simulation algorithms. When considering the beta spectra, discrepancies
      notably reduce: within 0.9.X90, FLUKA and PENELOPE differ for less than 1% in
      water and less than 2% in bone with any of the isotopes here considered. Complete
      data of FLUKA DPKS are given as Supplementary Material as a tool to perform
      dosimetry by analytical point kernel convolution. CONCLUSIONS: FLUKA provides
      reliable results when transporting electrons in the low energy range, proving to
      be an adequate tool for nuclear medicine dosimetry.

PMID- 21858992
TI  - Angular dependence of the nanoDot OSL dosimeter.
AB  - PURPOSE: Optically stimulated luminescent detectors (OSLDs) are quickly gaining
      popularity as passive dosimeters, with applications in medicine for linac output
      calibration verification, brachytherapy source verification, treatment plan
      quality assurance, and clinical dose measurements. With such wide applications,
      these dosimeters must be characterized for numerous factors affecting their
      response. The most abundant commercial OSLD is the InLight/OSL system from
      Landauer, Inc. The purpose of this study was to examine the angular dependence of
      the nanoDot dosimeter, which is part of the InLight system. METHODS: Relative
      dosimeter response data were taken at several angles in 6 and 18 MV photon beams,
      as well as a clinical proton beam. These measurements were done within a phantom
      at a depth beyond the build-up region. To verify the observed angular dependence,
      additional measurements were conducted as well as Monte Carlo simulations in
      MCNPX. RESULTS: When irradiated with the incident photon beams parallel to the
      plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at
      18 MV than the response when irradiated with the incident beam normal to the
      plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to
      the experimental values. Examination of the results in Monte Carlo suggests the
      cause as partial volume irradiation. In a clinical proton beam, no angular
      dependence was found. CONCLUSIONS: A nontrivial angular response of this OSLD was
      observed in photon beams. This factor may need to be accounted for when
      evaluating doses from photon beams incident from a variety of directions.

PMID- 21858993
TI  - Verification of the linac isocenter for stereotactic radiosurgery using cine-EPID
      imaging and arc delivery.
AB  - PURPOSE: Verification of the mechanical isocenter position is required as part of
      comprehensive quality assurance programs for stereotactic
      radiosurgery/radiotherapy (SRS/SRT) treatments. Several techniques have been
      proposed for this purpose but each of them has certain drawbacks. In this paper,
      a new efficient and more comprehensive method using cine-EPID images has been
      introduced for automatic verification of the isocenter with sufficient accuracy
      for stereotactic applications. METHODS: Using a circular collimator fixed to the
      gantry head to define the field, EPID images of a Winston-Lutz phantom were
      acquired in cine-imaging mode during 3600 gantry rotations. A robust MATLAB code
      was developed to analyze the data by finding the center of the field and the
      center of the ball bearing shadow in each image with sub-pixel accuracy. The
      distance between these two centers was determined for every image. The method was
      evaluated by comparison to results of a mechanical pointer and also by detection
      of a manual shift applied to the phantom position. The repeatability and
      reproducibility of the method were tested and it was also applied to detect couch
      and collimator wobble during rotation. RESULTS: The accuracy of the algorithm was
      0.03 +/- 0.02 mm. The repeatability was less than 3 pm and the reproducibility
      was less than 86 microm. The time elapsed for the analysis of more than 100 cine
      images of Varian aS1000 and aS500 EPIDs were approximately 65 and 20 s,
      respectively. Processing of images taken in integrated mode took 0.1 s. The
      output of the analysis software is printable and shows the isocenter shifts as a
      function of angle in both in-plane and cross-plane directions. It gives warning
      messages where the shifts exceed the criteria for SRS/SRT and provides useful
      data for the necessary adjustments in the system including bearing system and/or
      room lasers. CONCLUSIONS: The comprehensive method introduced in this study uses
      cine-images, is highly accurate, fast, and independent of the observer. It tests
      all gantry angles and is suitable for pretreatment QA of the isocenter for
      stereotactic treatments.

PMID- 21858994
TI  - Management of the baseline shift using a new and simple method for respiratory
      gated radiation therapy: detectability and effectiveness of a flexible monitoring
      system.
AB  - PURPOSE: In respiratory-gated radiation therapy, a baseline shift decreases the
      accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness
      of audio-feedback and audio-visual feedback in correcting the baseline shift in
      the breathing pattern of the patient has been demonstrated previously. However,
      the baseline shift derived from the intrafraction motion of the patient's body
      cannot be corrected by these methods. In the present study, the authors designed
      and developed a simple and flexible system. METHODS: The system consisted of a
      web camera and a computer running our in-house software. The in-house software
      was adapted to template matching and also to no preimage processing. The system
      was capable of monitoring the baseline shift in the intrafraction motion of the
      patient's body. Another marker box was used to monitor the baseline shift due to
      the flexible setups required of a marker box for gated signals. The system
      accuracy was evaluated by employing a respiratory motion phantom and was found to
      be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal
      accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the
      effectiveness of this flexible and independent system in gated treatment was
      investigated in healthy volunteers, in terms of the results from the differences
      in the baseline shift detectable between the marker positions, which the authors
      evaluated statistically. RESULTS: The movement of the marker on the sternum
      [1.599 +/- 0.622 mm (1 SD)] was substantially decreased as compared with the
      abdomen [6.547 +/- 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the
      baseline shifts for the sternum [-0.136 +/- 0.868 (2 SD)] were in better
      agreement with the nominal baseline shifts than was the case for the abdomen [
      0.722 +/- 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and
      detected using the monitoring system, which could acquire the movement of the
      marker on the sternum. The baseline shift-monitoring system with the displacement
      based methods for highly accurate respiratory-gated treatments should be used to
      make most of the displacement-based gating methods. CONCLUSIONS: The advent of
      intensity modulated radiation therapy and volumetric modulated radiation therapy
      facilitates margin reduction for the planning target volumes and the OARs, but
      highly accurate irradiation is needed to achieve target coverage and OAR sparing
      with a small margin. The baseline shifts can affect treatment not only with the
      respiratory gating system but also without the system. Our system can manage the
      baseline shift and also enables treatment irradiation to be undertaken with high
      accuracy.

PMID- 21858995
TI  - Motion monitoring for cranial frameless stereotactic radiosurgery using video
      based three-dimensional optical surface imaging.
AB  - PURPOSE: To establish a new clinical procedure in frameless stereotactic
      radiosurgery (SRS) for patient setup verification at treatment couch angles as
      well as for head-motion monitoring during treatment using video-based optical
      surface imaging (OSI). METHODS: A video-based three-dimensional (3D) OSI system
      with three ceiling-mounted camera pods was employed to verify setup at treatment
      couch angles as well as to monitor head motion during treatment. A noninvasive
      head immobilization device was utilized, which includes an alpha head mold and a
      dental mouthpiece with vacuum suction; both were locked to the treatment couch.
      Cone beam computed tomography (CBCT) was used as the standard for image-guided
      setup. Orthogonal 2D-kV imaging was applied for setup verification before
      treatment, between couch rotations, and after treatment at zero couch angle. At
      various treatment couch angles, OSI setup verification was performed, relative to
      initial OSI setup verification at zero couch angle after CBCT setup through a
      coordinate transformation. For motion monitoring, the setup uncertainty was
      decoupled by taking an on-site surface image as new reference to detect motion
      induced misalignment in near real-time (1-2 frames per second). Initial thermal
      instability baseline of the real-time monitoring was corrected. An
      anthropomorphous head phantom and a 1D positioning platform were used to assess
      the OSI accuracy in motion detection in longitudinal and lateral directions. Two
      hypofractionated (9 Gy x 3 and 6 Gy x 5) frameless stereotactic radiotherapy
      (SRT) patients as well as two single-fraction (21 and 18 Gy) frameless SRS
      patients were treated using this frameless procedure. For comparison, 11
      conventional frame-based SRS patients were monitored using the OSI to serve as
      clinical standards. Multiple noncoplanar conformal beams were used for planning
      both frameless and frame-based SRS with a micromultileaf collimator. RESULTS: The
      accuracy of the OSI in 1D motion detection was found to be 0.1 mm with
      uncertainty of +/- 0.1 mm using the head phantom. The OSI registration against
      simulation computed tomography (CT) external contour was found to be dependent on
      the CT skin definition with -0.4 mm variation. For frame-based SRS patients, head
      motion magnitude was detected to be <1.0 mm (0.3 +/- 0.2 mm) and <1.0 degree (0.2
      degrees +/- 0.2 degrees) for 98% of treatment time, with exception of one patient
      with head rotation <1.5 degrees for 98% of the time. For frameless SRT/SRS
      patients, similar motion magnitudes were observed with an average of 0.3 +/- 0.2
      mm and 0.2 degrees +/- 0.1 degree in ten treatments. For 98% of the time, the
      motion magnitude was <1.1 mm and 1.0 degree. Complex head-motion patterns within
      1.0 mm were observed for frameless SRT/SRS patients. The OSI setup verification
      at treatment couch angles was found to be within 1.0 mm. CONCLUSIONS: The OSI
      system is capable of detecting 0.1 +/- 0.1 mm 1D spatial displacement of a
      phantom in near real time and useful in head-motion monitoring. This new
      frameless SRS procedure using the mask-less head-fixation system provides
      immobilization similar to that of conventional frame-based SRS. Head-motion
      monitoring using near-real-time surface imaging provides adequate accuracy and is
      necessary for frameless SRS in case of unexpected head motion that exceeds a set
      tolerance.

PMID- 21858996
TI  - Optimized RF shielding techniques for simultaneous PET/MR.
AB  - PURPOSE: Integration of positron emission tomography (PET) and magnetic resonance
      (MR) in a merged device requires shielding of the PET detector electronics. The
      authors demonstrate that a multiple shell setup exhibits advantages over a single
      shell shielding enclosure. METHODS: A spherical shell model is used to derive
      analytical results. Numerical computations of the electromagnetic fields with a
      commercial software package (FEKO) and experiments are used to confirm our
      findings. RESULTS: Replacing a single shell enclosure by a multilayer approach
      barely changes its behavior toward low frequency magnetic fields (MR gradient
      fields), while improving shielding at high frequencies (proton resonant
      frequency) by orders of magnitude. CONCLUSIONS: For a given required shielding
      factor at the proton resonant frequency, the eddy currents induced by the MR
      gradient fields may be reduced by employing a multiple shell setup.

PMID- 21858997
TI  - Determination of action thresholds for electromagnetic tracking system-guided
      hypofractionated prostate radiotherapy using volumetric modulated arc therapy.
AB  - PURPOSE: Hypofractionated prostate radiotherapy may benefit from both volumetric
      modulated are therapy (VMAT) due to shortened treatment time and intrafraction
      real-time monitoring provided by implanted radiofrequency(RF) transponders. The
      authors investigate dosimetrically driven action thresholds (whether treatment
      needs to be interrupted and patient repositioned) in VMAT treatment with
      electromagnetic (EM) tracking. METHODS: VMAT plans for five patients are
      generated for prescription doses of 32.5 and 42.5 Gy in five fractions. Planning
      target volume (PTV) encloses the clinical target volume (CTV) with a 3 mm margin
      at the prostate-rectal interface and 5 mm elsewhere. The VMAT delivery is modeled
      using 180 equi-spaced static beams. Intrafraction prostate motion is simulated in
      the plan by displacing the beam isocenter at each beam assuming rigid organ
      motion according to a previously recorded trajectory of the transponder centroid.
      The cumulative dose delivered in each fraction is summed over all beams. Two sets
      of 57 prostate motion trajectories were randomly selected to form a learning and
      a testing dataset. Dosimetric end points including CTV D95%, rectum wall D1cc,
      bladder wall D1cc, and urethra Dmax, are analyzed against motion characteristics
      including the maximum amplitude of the anterior-posterior (AP), superior-inferior
      (SI), and left-right components. Action thresholds are triggered when
      intrafraction motion causes any violations of dose constraints to target and
      organs at risk (OAR), so that treatment is interrupted and patient is
      repositioned. RESULTS: Intrafraction motion has a little effect on CTV D95%,
      indicating PTV margins are adequate. Tight posterior and inferior action
      thresholds around 1 mm need to be set in a patient specific manner to spare
      organs at risk, especially when the prescription dose is 42.5 Gy. Advantages of
      setting patient specific action thresholds are to reduce false positive alarms by
      25% when prescription dose is low, and increase the sensitivity of detecting dose
      limits violations by 30% when prescription dose is high, compared to a generic 2
      mm action box. The sensitivity and specificity calculated from the testing
      dataset are consistent to the learning set, which indicates that the patient
      specific approach is reliable and reproducible within the scope of the prostate
      database. CONCLUSIONS: This work introduces a formalism for ensuring a VMAT
      delivery meets the most clinically important dose requirements by using patient
      specific and dosimetric-driven action thresholds to hold the beam and reposition
      the patient when necessary. Such methods can provide improved sensitivity and
      specificity compared to conventional methods, which assume directionally
      symmetric action thresholds.

PMID- 21858998
TI  - First assessment of three-dimensional quantitative photoacoustic tomography for
      in vivo detection of osteoarthritis in the finger joints.
AB  - PURPOSE: The purpose of this pilot clinical study is to assess three-dimensional
      (3-D) quantitative photoacoustic tomography (qPAT) for in vivo detection of
      osteoarthritis (OA) in the finger joints. METHODS: All subject data were handled
      in compliance with the rules and regulations concerning the privacy and security
      of protected health information under HIPAA. Seven female subjects (two OA
      patients and five healthy controls) entered the study and their distal
      interphalangeal (DIP) joints were examined by a 3-D photoacoustic scanner. 3-D
      optical absorption coefficient images of all the photoacoustically examined
      joints were recovered using a 3-D qPAT reconstruction algorithm. RESULTS: The
      recovered quantitative photoacoustic images revealed obvious difference in the
      optical absorption coefficient of the joint cavity (cartilage and synovial fluid)
      between the OA and healthy joints. Quantitative analysis of the joints also
      indicated an apparent difference in the recovered joint spacing between the OA
      and healthy subjects. CONCLUSION: This initial clinical evaluation suggests that
      it is feasible to detect osteoarthritis in the finger joints with our 3-D qPAT
      approach, which has paved the way to further statistically evaluate the
      diagnostic performance of the 3-D qPAT approach in comparison with radiography or
      magnetic resonance imaging (MRI) on a sample of hand osteoarthritis.

PMID- 21858999
TI  - Modeling the truebeam linac using a CAD to Geant4 geometry implementation: dose
      and IAEA-compliant phase space calculations.
AB  - PURPOSE: To create an accurate 6 MV Monte Carlo simulation phase space for the
      Varian TrueBeam treatment head geometry imported from CAD (computer aided design)
      without adjusting the input electron phase space parameters. METHODS: GEANT4
      v4.9.2.p01 was employed to simulate the 6 MV beam treatment head geometry of the
      Varian TrueBeam linac. The electron tracks in the linear accelerator were
      simulated with Parmela, and the obtained electron phase space was used as an
      input to the Monte Carlo beam transport and dose calculations. The geometry
      components are tessellated solids included in GEANT4 as GDML (generalized dynamic
      markup language) files obtained via STEP (standard for the exchange of product)
      export from Pro/Engineering, followed by STEP import in Fastrad, a STEP-GDML
      converter. The linac has a compact treatment head and the small space between the
      shielding collimator and the divergent are of the upper jaws forbids the
      implementation of a plane for storing the phase space. Instead, an IAEA
      (International Atomic Energy Agency) compliant phase space writer was implemented
      on a cylindrical surface. The simulation was run in parallel on a 1200 node Linux
      cluster. The 6 MV dose calculations were performed for field sizes varying from 4
      x 4 to 40 x 40 cm2. The voxel size for the 60 x 60 x 40 cm3 water phantom was 4 x
      4 x 4 mm3. For the 10 x 10 cm2 field, surface buildup calculations were performed
      using 4 x 4 x 2 mm3 voxels within 20 mm of the surface. RESULTS: For the depth
      dose curves, 98% of the calculated data points agree within 2% with the
      experimental measurements for depths between 2 and 40 cm. For depths between 5
      and 30 cm, agreement within 1% is obtained for 99% (4 x 4), 95% (10 x 10), 94%
      (20 x 20 and 30 x 30), and 89% (40 x 40) of the data points, respectively. In the
      buildup region, the agreement is within 2%, except at 1 mm depth where the
      deviation is 5% for the 10 x 10 cm2 open field. For the lateral dose profiles,
      within the field size for fields up to 30 x 30 cm2, the agreement is within 2%
      for depths up to 10 cm. At 20 cm depth, the in-field maximum dose difference for
      the 30 x 30 cm2 open field is within 4%, while the smaller field sizes agree
      within 2%. Outside the field size, agreement within 1% of the maximum dose
      difference is obtained for all fields. The calculated output factors varied from
      0.938 +/- 0.015 for the 4 x 4 cm2 field to 1.088 +/- 0.024 for the 40 x 40 cm2
      field. Their agreement with the experimental output factors is within 1%.
      CONCLUSIONS: The authors have validated a GEANT4 simulated IAEA-compliant phase
      space of the TrueBeam linac for the 6 MV beam obtained using a high accuracy
      geometry implementation from CAD. These files are publicly available and can be
      used for further research.

PMID- 21859000
TI  - Planning strategies in volumetric modulated are therapy for breast.
AB  - PURPOSE: In breast radiotherapy with intensity modulation, it is a well
      established practice to extend the dose fluence outside the limit of the body
      contour to account for small changes in size and position of the target and the
      rest of the tissues due to respiration or to possible oedema. A simple approach
      is not applicable with RapidArc volumetric modulated are therapy not being based
      on a fixed field fluence delivery. In this study, a viable technical strategy to
      account for this need is presented. METHODS: RapidArc (RA) plans for six breast
      cancer patients (three right and three left cases), were optimized (PRO version
      III) on the original CT data set (0) and on an alternative CT (E) generated with
      an artificial expansion (and assignment of soft-tissue equivalent HU) of 10 mm of
      the body in the breast region and of the PTV contours toward the external
      direction. Final dose calculations for the two set of plans were performed on the
      same original CT data set O, normalizing the dose prescription (50 Gy) to the
      target mean. In this way, two treatment plans on the same CT set O for each
      patient were obtained: the no action plan (OO) and the alternative plan based on
      an expanded optimization (EO). Fixing MU, these two plans were then recomputed on
      the expanded CT data set and on an intermediate one (with expansion = 5 mm), to
      mimic, possible changes in size due to edema during treatment or residual
      displacements due to breathing not properly controlled. Aim of the study was to
      quantify the robustness of this planning strategy on dose distributions when
      either the OO or the EO strategies were adopted. For all the combinations, a DVH
      analysis of all involved structures is reported. RESULTS: I. The two optimization
      approaches gave comparable dose distributions on the original CT data set. II.
      When plans were evaluated on the expanded CTs (mimicking the presence of edema),
      the EO approach showed improved target coverage if compared to OO: on CT_10 mm,
      Dv = 98% [%]= 92.5 +/- 0.9 and 68.5 +/- 3.1, respectively, for EO and OO. Minor
      changes were registered in organs at risk sparing for both EO and OO. III. From
      dose distributions and DVHs, EO approach allowed to irradiate at near to
      prescription levels also the expanded fraction of the target: this would account
      also for residual intrafraction movements. CONCLUSIONS: The proposed plan
      strategy could represent a robust approach to account for moderate changes in
      target or body volume during the course of breast radiotherapy and to account for
      residual intrafractional respiratory motion in volumetric modulated are therapy.
      The strategy, logistically simple to implement requiring only modifications to
      the standard planning workflow was routinely implemented at author's institute
      for treatment of breast patients with RapidArc.

PMID- 21859001
TI  - A fast three-dimensional gamma evaluation using a GPU utilizing texture memory
      for on-the-fly interpolations.
AB  - PURPOSE: A widely accepted method to quantify differences in dose distributions
      is the gamma (gamma) evaluation. Currently, almost all gamma implementations
      utilize the central processing unit (CPU). Recently, the graphics processing unit
      (GPU) has become a powerful platform for specific computing tasks. In this study,
      we describe the implementation of a 3D gamma evaluation using a GPU to improve
      calculation time. METHODS: The gamma evaluation algorithm was implemented on an
      NVIDIA Tesla C2050 GPU using the compute unified device architecture (CUDA).
      First, several cubic virtual phantoms were simulated. These phantoms were tested
      with varying dose cube sizes and set-ups, introducing artificial dose
      differences. Second, to show applicability in clinical practice, five patient
      cases have been evaluated using the 3D dose distribution from a treatment
      planning system as the reference and the delivered dose determined during
      treatment as the comparison. A calculation time comparison between the CPU and
      GPU was made with varying thread-block sizes including the option of using
      texture or global memory. RESULTS: A GPU over CPU speed-up of 66 +/- 12 was
      achieved for the virtual phantoms. For the patient cases, a speed-up of 57 +/- 15
      using the GPU was obtained. A thread-block size of 16 x 16 performed best in all
      cases. The use of texture memory improved the total calculation time, especially
      when interpolation was applied. Differences between the CPU and GPU gammas were
      negligible. CONCLUSIONS: The GPU and its features, such as texture memory,
      decreased the calculation time for gamma evaluations considerably without loss of
      accuracy.

PMID- 21859002
TI  - Correlation and prediction uncertainties in the cyberknife synchrony respiratory
      tracking system.
AB  - PURPOSE: The CyberKnife uses an online prediction model to improve radiation
      delivery when treating lung tumors. This study evaluates the prediction model
      used by the CyberKnife radiation therapy system in terms of treatment margins
      about the gross tumor volume (GTV). METHODS: From the data log files produced by
      the CyberKnife synchrony model, the uncertainty in radiation delivery can be
      calculated. Modeler points indicate the tracked position of the tumor and
      Predictor points predict the position about 115 ms in the future. The discrepancy
      between Predictor points and their corresponding Modeler points was analyzed for
      100 treatment model data sets from 23 de-identified lung patients. The treatment
      margins were determined in each anatomic direction to cover an arbitrary volume
      of the GTV, derived from the Modeler points, when the radiation is targeted at
      the Predictor points. Each treatment model had about 30 min of motion data, of
      which about 10 min constituted treatment time; only these 10 min were used in the
      analysis. The frequencies of margin sizes were analyzed and truncated Gaussian
      normal functions were fit to each direction's distribution. The standard
      deviation of each Gaussian distribution was then used to describe the necessary
      margin expansions in each signed dimension in order to achieve the desired
      coverage. In this study, 95% modeler point coverage was compared to 99% modeler
      coverage. Two other error sources were investigated: the correlation error and
      the targeting error. These were added to the prediction error to give an
      aggregate error for the CyberKnife during treatment of lung tumors. RESULTS:
      Considering the magnitude of 2sigma from the mean of the Gaussian in each signed
      dimension, the margin expansions needed for 95% modeler point coverage were 1.2
      mm in the lateral (LAT) direction and 1.7 mm in the anterior-posterior (AP)
      direction. For the superior-inferior (SI) direction, the fit was poor; but
      empirically, the expansions were 3.5 mm. For 99% modeler point coverage, the AP
      margin was 3.6 mm and the lateral margin was 2.9 mm. The SI margins for 99%
      modeler point coverage were highly variable. The aggregate error at 95% was 6.9
      mm in the SI direction, 4.6 mm in the AP direction, and 3.5 in the lateral
      direction. CONCLUSIONS: The Predictor points follow the Modeler points closely.
      Margins were found in each clinical direction that would provide 95% modeler
      point coverage for 95% of the models reviewed in this study. Similar margins were
      found in two clinical directions for 99% modeler point coverage in 95% of models.
      These results can offer guidance in the selection of CTV margins for treatment
      with the CyberKnife.

PMID- 21859003
TI  - IPIP: A new approach to inverse planning for HDR brachytherapy by directly
      optimizing dosimetric indices.
AB  - PURPOSE: Many planning methods for high dose rate (HDR) brachytherapy require an
      iterative approach. A set of computational parameters are hypothesized that will
      give a dose plan that meets dosimetric criteria. A dose plan is computed using
      these parameters, and if any dosimetric criteria are not met, the process is
      iterated until a suitable dose plan is found. In this way, the dose distribution
      is controlled by abstract parameters. The purpose of this study is to develop a
      new approach for HDR brachytherapy by directly optimizing the dose distribution
      based on dosimetric criteria. METHODS: The authors developed inverse planning by
      integer program (IPIP), an optimization model for computing HDR brachytherapy
      dose plans and a fast heuristic for it. They used their heuristic to compute dose
      plans for 20 anonymized prostate cancer image data sets from patients previously
      treated at their clinic database. Dosimetry was evaluated and compared to
      dosimetric criteria. RESULTS: Dose plans computed from IPIP satisfied all given
      dosimetric criteria for the target and healthy tissue after a single iteration.
      The average target coverage was 95%. The average computation time for IPIP was
      30.1 s on an Intel(R) Core 2 Duo CPU 1.67 GHz processor with 3 Gib RAM.
      CONCLUSIONS: IPIP is an HDR brachytherapy planning system that directly
      incorporates dosimetric criteria. The authors have demonstrated that IPIP has
      clinically acceptable performance for the prostate cases and dosimetric criteria
      used in this study, in both dosimetry and runtime. Further study is required to
      determine if IPIP performs well for a more general group of patients and
      dosimetric criteria, including other cancer sites such as GYN.

PMID- 21859004
TI  - A fast forward projection using multithreads for multirays on GPUs in medical
      image reconstruction.
AB  - PURPOSE: Iterative reconstruction techniques hold great potential to mitigate the
      effects of data noise and/or incompleteness, and hence can facilitate the patient
      dose reduction. However, they are not suitable for routine clinical practice due
      to their long reconstruction times. In this work, the authors accelerated the
      computations by fully taking advantage of the highly parallel computational power
      on single and multiple graphics processing units (GPUs). In particular, the
      forward projection algorithm, which is not included in the close-form formulas,
      will be accelerated and optimized by using GPU here. METHODS: The main
      contribution is a novel forward projection algorithm that uses multithreads to
      handle the computations associated with a bunch of adjacent rays simultaneously.
      The proposed algorithm is free of divergence and bank conflict on GPU, and
      benefits from data locality and data reuse. It achieves the efficiency
      particularly by (i) employing a tiled algorithm with three-level parallelization,
      (ii) optimizing thread block size, (iii) maximizing data reuse on constant memory
      and shared memory, and (iv) exploiting built-in texture memory interpolation
      capability to increase efficiency. In addition, to accelerate the iterative
      algorithms and the Feldkamp-Davis-Kress (FDK) algorithm on GPU, the authors apply
      batched fast Fourier transform (FFT) to expedite filtering process in FDK and
      utilize projection bundling parallelism during backprojection to shorten the
      execution times in FDK and the expectation-maximization (EM). RESULTS: Numerical
      experiments conducted on an NVIDIA Tesla C1060 GPU demonstrated the superiority
      of the proposed algorithms in computational time saving. The forward projection,
      filtering, and backprojection times for generating a volume image of 512 x 512 x
      512 with 360 projection data of 512 x 512 using one GPU are about 4.13, 0.65, and
      2.47 s (including distance weighting), respectively. In particular, the proposed
      forward projection algorithm is ray-driven and its paralleli-zation strategy
      evolves from single-thread-for-single-ray (38.56 s), multithreads-for-single-ray
      (26.05 s), to multithreads-for-multirays (4.13 s). For the voxel-driven
      backprojection, the use of texture memory reduces the reconstruction time from
      4.95 to 3.35 s. By applying the projection bundle technique, the computation time
      is further reduced to 2.47 s. When employing multiple GPUs, near-perfect speedups
      were observed as the number of GPUs increases. For example, by using four GPUs,
      the time for the forward projection, filtering, and backprojection are further
      reduced to 1.11, 0.18, and 0.66 s. The results obtained by GPU-based algorithms
      are virtually indistinguishable with those by CPU. CONCLUSIONS: The authors have
      proposed a highly optimized GPU-based forward projection algorithm, as well as
      the GPU-based FDK and expectation-maximization reconstruction algorithms. Our
      compute unified device architecture (CUDA) codes provide the exceedingly fast
      forward projection and backprojection that outperform those using the shading
      languages, cell broadband engine architecture and previous CUDA implementations.
      The reconstruction times in the FDK and the EM algorithms were considerably
      shortened, and thus can facilitate their routine usage in a variety of
      applications such as image quality improvement and dose reduction.

PMID- 21859005
TI  - Inverse determination of the penalty parameter in penalized weighted least
      squares algorithm for noise reduction of low-dose CBCT.
AB  - PURPOSE: A statistical projection restoration algorithm based on the penalized
      weighted least-squares (PWLS) criterion can substantially improve the image
      quality of low-dose CBCT images. The performance of PWLS is largely dependent on
      the choice of the penalty parameter. Previously, the penalty parameter was chosen
      empirically by trial and error. In this work, the authors developed an inverse
      technique to calculate the penalty parameter in PWLS for noise suppression of low
      dose CBCT in image guided radiotherapy (IGRT). METHODS: In IGRT, a daily CBCT is
      acquired for the same patient during a treatment course. In this work, the
      authors acquired the CBCT with a high-mAs protocol for the first session and then
      a lower mAs protocol for the subsequent sessions. The high-mAs projections served
      as the goal (ideal) toward, which the low-mAs projections were to be smoothed by
      minimizing the PWLS objective function. The penalty parameter was determined
      through an inverse calculation of the derivative of the objective function
      incorporating both the high and low-mAs projections. Then the parameter obtained
      can be used for PWLS to smooth the noise in low-dose projections. CBCT
      projections for a CatPhan 600 and an anthropomorphic head phantom, as well as for
      a brain patient, were used to evaluate the performance of the proposed technique.
      RESULTS: The penalty parameter in PWLS was obtained for each CBCT projection
      using the proposed strategy. The noise in the low-dose CBCT images reconstructed
      from the smoothed projections was greatly suppressed. Image quality in PWLS
      processed low-dose CBCT was comparable to its corresponding high-dose CBCT.
      CONCLUSIONS: A technique was proposed to estimate the penalty parameter for PWLS
      algorithm. It provides an objective and efficient way to obtain the penalty
      parameter for image restoration algorithms that require predefined smoothing
      parameters.

PMID- 21859006
TI  - Usefulness of specific calibration coefficients for gamma-emitting sources
      measured by radionuclide calibrators in nuclear medicine.
AB  - PURPOSE: In nuclear medicine, the activity of a radionuclide is measured with a
      radionuclide calibrator that often has a calibration coefficient independent of
      the container type and filling. METHODS: To determine the effect of the container
      on the accuracy of measuring the activity injected into a patient, The authors
      simulated a commercial radionuclide calibrator and 18 container types most
      typically used in clinical practice. The instrument sensitivity was computed for
      various container thicknesses and filling levels. Monoenergetic photons and
      electrons as well as seven common radionuclides were considered. RESULTS: The
      quality of the simulation with gamma-emitting sources was validated by an
      agreement with measurements better than 4% in five selected radionuclides. The
      results show that the measured activity can vary by more than a factor of 2
      depending on the type of container. The filling level and the thickness of the
      container wall only have a marginal effect for radionuclides of high energy but
      could induce differences up to 4%. CONCLUSIONS: The authors conclude that
      radionuclide calibrators should be tailored to the uncertainty required by
      clinical applications. For most clinical cases, and at least for the low-energy
      gamma and x-ray emitters, measurements should be performed with calibration
      coefficients specific to the container type.

PMID- 21859007
TI  - High dose per fraction dosimetry of small fields with gafchromic EBT2 film.
AB  - PURPOSE: Small field dosimetry is prone to uncertainties due to the lack of
      electronic equilibrium and the use of the correct detector size relative to the
      field size measured. It also exhibits higher sensitivity to setup errors as well
      as large variation in output with field size and shape. Radiochromic film is an
      attractive method for reference dosimetry in small fields due to its ability to
      provide 2D dose measurements while having minimal impact on the dose
      distribution. Gafchromic EBT2 has a dose range of up to 40 Gy; therefore, it
      could potentially be useful for high dose reference dosimetry with high spatial
      resolution. This is a requirement in stereotactic radiosurgery deliveries, which
      deliver high doses per fraction to small targets. METHODS: Targets of 4 mm and 12
      mm diameters were treated to a minimum peripheral dose of 21 Gy prescribed to 80%
      of the maximum dose in one fraction. Target doses were measured with EBT2 film
      (both targets) and an ion chamber (12 mm target only). Measured doses were
      compared with planned dose distributions using profiles through the target and
      minimum peripheral dose coverage. RESULTS: The measured target doses and isodose
      coverage agreed with the planned dose within +/-1 standard deviation of three
      measurements, which were 2.13% and 2.5% for the 4 mm and 12 mm targets,
      respectively. CONCLUSIONS: EBT2 film is a feasible dosimeter for high dose per
      fraction reference 2D dosimetry.

PMID- 21859008
TI  - ICE decoupling technique for RF coil array designs.
AB  - PURPOSE: Parallel magnetic resonance imaging (MRI) requires an array of RF coil
      elements with different sensitivity distributions and with minimal
      electromagnetic coupling. The goal of this project was to develop a new method
      based on induced current compensation or elimination (ICE) for improved coil
      element decoupling and to investigate its performance in phantom MR images.
      METHODS: An electromagnetic decoupling method based on induced current
      compensation or elimination for nonoverlapping RF coil arrays was developed with
      the design criteria of high efficiency, easy implementation, and no physical
      connection to RF array elements. An eigenvalue/eigenvector approach was employed
      to analyze the decoupling mechanism and condition. A two-channel microstrip array
      and an eight-channel coil array were built to test the performance of the method.
      Following workbench tests, MR imaging experiments were performed on a 7T MR
      scanner. RESULTS: The bench tests showed that both arrays achieved sufficient
      decoupling with a S21 less than -25 dB among the coil elements at 298 MHz. The MR
      phantom images demonstrated well-defined sensitivity distributions from each coil
      element and the unique decoupling capability of the proposed ICE decoupling
      technique. B1 distributions of the individual elements were also measured and
      calculated. CONCLUSIONS: The theoretical analysis and experiments demonstrated
      the feasibility of the decoupling method for high field RF coil array designs
      without overlapping or direct physical connections between coil elements, which
      provide more flexibility for coil array design and optimization. The method
      offers a new approach to address the RF array decoupling issue, which is a major
      challenge in implementing parallel imaging.

PMID- 21859009
TI  - Determination of equivalent breast phantoms for different age groups of Taiwanese
      women: an experimental approach.
AB  - PURPOSE: Polymethylmethacrylate (PMMA) slab is one of the mostly used phantoms
      for studying breast dosimetry in mammography. The purpose of this study was to
      evaluate the equivalence between exposure factors acquired from PMMA slabs and
      patient cases of different age groups of Taiwanese women in mammography. METHODS:
      This study included 3910 craniocaudal screen/film mammograms on Taiwanese women
      acquired on one mammographic unit. The tube loading, compressed breast thickness
      (CBT), compression force, tube voltage, and target/filter combination for each
      mammogram were collected for all patients. The glandularity and the equivalent
      thickness of PMMA were determined for each breast using the exposure factors of
      the breast in combination with experimental measurements from breast-tissue
      equivalent attenuation slabs. Equivalent thicknesses of PMMA to the breasts of
      Taiwanese women were then estimated. RESULTS: The average +/- standard deviation
      CBT and breast glandularity in this study were 4.2 +/- 1.0 cm and 54% +/- 23%,
      respectively. The average equivalent PMMA thickness was 4.0 +/- 0.7 cm. PMMA
      slabs producing equivalent exposure factors as in the breasts of Taiwanese women
      were determined for the age groups 30-49 yr and 50-69 yr. For the 4-cm PMMA slab,
      the CBT and glandularity values of the equivalent breast were 4.1 cm and 65%,
      respectively, for the age group 30-49 yr and 4.4 cm and 44%, respectively, for
      the age group 50-69 yr. CONCLUSIONS: The average thickness of PMMA slabs
      producing the same exposure factors as observed in a large group of Taiwanese
      women is less than that reported for American women. The results from this study
      can provide useful information for determining a suitable thickness of PMMA for
      mammographic dose survey in Taiwan. The equivalence of PMMA slabs and the breasts
      of Taiwanese women is provided to allow average glandular dose assessment in
      clinical practice.

PMID- 21859010
TI  - Validation of GPUMCD for low-energy brachytherapy seed dosimetry.
AB  - PURPOSE: To validate GPUMCD, a new package for fast Monte Carlo dose calculations
      based on the GPU (graphics processing unit), as a tool for low-energy single seed
      brachytherapy dosimetry for specific seed models. As the currently accepted
      method of dose calculation in low-energy brachytherapy computations relies on
      severe approximations, a Monte Carlo based approach would result in more accurate
      dose calculations, taking in to consideration the patient anatomy as well as
      interseed attenuation. The first step is to evaluate the capability of GPUMCD to
      reproduce low-energy, single source, brachytherapy calculations which could
      ultimately result in fast and accurate, Monte Carlo based, brachytherapy dose
      calculations for routine planning. METHODS: A mixed geometry engine was
      integrated to GPUMCD capable of handling parametric as well as voxelized
      geometries. In order to evaluate GPUMCD for brachytherapy calculations, several
      dosimetry parameters were computed and compared to values found in the
      literature. These parameters, defined by the AAPM Task-Group No. 43, are the
      radial dose function, the 2D anisotropy function, and the dose rate constant.
      These three parameters were computed for two different brachytherapy sources: the
      Amersham OncoSeed 6711 and the Imagyn IsoStar IS-12501. RESULTS: GPUMCD was shown
      to yield dosimetric parameters similar to those found in the literature. It
      reproduces radial dose functions to within 1.25% for both sources in the 0.5< r
      <10 cm range. The 2D anisotropy function was found to be within 3% at r =5 cm and
      within 4% at r = 1 cm. The dose rate constants obtained were within the range of
      other values reported in the literature. CONCLUSION: GPUMCD was shown to be able
      to reproduce various TG-43 parameters for two different low-energy brachytherapy
      sources found in the literature. The next step is to test GPUMCD as a fast
      clinical Monte Carlo brachytherapy dose calculations with multiple seeds and
      patient geometry, potentially providing more accurate results than the TG-43
      formalism while being much faster than calculations using general purpose Monte
      Carlo codes.

PMID- 21859011
TI  - Case report of a near medical event in stereotactic radiotherapy due to improper
      units of measure from a treatment planning system.
AB  - PURPOSE: The authors hereby notify the Radiation Oncology community of a
      potentially lethal error due to improper implementation of linear units of
      measure in a treatment planning system. The authors report an incident in which a
      patient was nearly mistreated during a stereotactic radiotherapy procedure due to
      inappropriate reporting of stereotactic coordinates by the radiation therapy
      treatment planning system in units of centimeter rather than in millimeter. The
      authors suggest a method to detect such errors during treatment planning so they
      are caught and corrected prior to the patient positioning for treatment on the
      treatment machine. METHODS: Using pretreatment imaging, the authors found that
      stereotactic coordinates are reported with improper linear units by a treatment
      planning system. The authors have implemented a redundant, independent method of
      stereotactic coordinate calculation. RESULTS: Implementation of a double check of
      stereotactic coordinates via redundant, independent calculation is simple and
      accurate. Use of this technique will avoid any future error in stereotactic
      treatment coordinates due to improper linear units, transcription, or other
      similar errors. CONCLUSIONS: The authors recommend an independent double check of
      stereotactic treatment coordinates during the treatment planning process in order
      to avoid potential mistreatment of patients.

PMID- 21859012
TI  - A theoretical and experimental evaluation of the microangiographic fluoroscope: A
      high-resolution region-of-interest x-ray imager.
AB  - PURPOSE: The increasing need for better image quality and high spatial resolution
      for successful endovascular image-guided interventions (EIGIs) and the inherent
      limitations of the state-of-the-art detectors provide motivation to develop a
      detector system tailored to the specific, demanding requirements of
      neurointerventional applications. METHOD: A microangiographic fluoroscope (MAF)
      was developed to serve as a high-resolution, region-of-interest (ROI) x-ray
      imaging detector in conjunction with large lower-resolution full field-of-view
      (FOV) state-of-the-art x-ray detectors. The newly developed MAF is an indirect x
      ray imaging detector capable of providing real-time images (30 frames per second)
      with high-resolution, high sensitivity, no lag and low instrumentation noise. It
      consists of a CCD camera coupled to a Gen 2 dual-stage microchannel plate light
      image intensifier (LII) through a fiber-optic taper. A 300 microm thick CsI(T1)
      phosphor serving as the front end is coupled to the LII. The LII is the key
      component of the MAF and the large variable gain provided by it enables the MAF
      to operate as a quantum-noise-limited detector for both fluoroscopy and
      angiography. RESULTS: The linear cascade model was used to predict the
      theoretical performance of the MAF, and the theoretical prediction showed close
      agreement with experimental findings. Linear system metrics such as MTF and DQE
      were used to gauge the detector performance up to 10 cycles/mm. The measured zero
      frequency DQE(0) was 0.55 for an RQA5 spectrum. A total of 21 stages were
      identified for the whole imaging chain and each stage was characterized
      individually. CONCLUSIONS: The linear cascade model analysis provides insight
      into the imaging chain and may be useful for further development of the MAF
      detector. The preclinical testing of the prototype detector in animal procedures
      is showing encouraging results and points to the potential for significant impact
      on EIGIs when used in conjunction with a state-of-art flat panel detector (FPD).

PMID- 21859013
TI  - Cerenkov emission induced by external beam radiation stimulates molecular
      fluorescence.
AB  - PURPOSE: Cerenkov emission is induced when a charged particle moves faster than
      the speed of light in a given medium. Both x-ray photons and electrons produce
      optical Cerenkov photons in everyday radiation therapy of tissue; yet, this
      phenomenon has never been fully documented. This study quantifies the emissions
      and also demonstrates that the Cerenkov emission can excite a fluorophore,
      protoporphyrin IX (PpIX), embedded in biological phantoms. METHODS: In this
      study, Cerenkov emission induced by radiation from a clinical linear accelerator
      is investigated. Biological mimicking phantoms were irradiated with x-ray
      photons, with energies of 6 or 18 MV, or electrons at energies 6, 9, 12, 15, or
      18 MeV. The Cerenkov emission and the induced molecular fluorescence were
      detected by a camera or a spectrometer equipped with a fiber optic cable.
      RESULTS: It is shown that both x-ray photons and electrons, at MeV energies,
      produce optical Cerenkov photons in tissue mimicking media. Furthermore, we
      demonstrate that the Cerenkov emission can excite a fluorophore, protoporphyrin
      IX (PpIX), embedded in biological phantoms. CONCLUSIONS: The results here
      indicate that molecular fluorescence monitoring during external beam radiotherapy
      is possible.

PMID- 21859014
TI  - Noise in x-ray grating-based phase-contrast imaging.
AB  - PURPOSE: Grating-based x-ray phase-contrast imaging is a fast developing new
      modality not only for medical imaging, but as well for other fields such as
      material sciences. While these many possible applications arise, the knowledge of
      the noise behavior is essential. METHODS: In this work, the authors used a least
      squares fitting algorithm to calculate the noise behavior of the three quantities
      absorption, differential phase, and dark-field image. Further, the calculated
      error formula of the differential phase image was verified by measurements.
      Therefore, a Talbot interferometer was setup, using a microfocus x-ray tube as
      source and a Timepix detector for photon counting. Additionally, simulations
      regarding this topic were performed. RESULTS: It turned out that the variance of
      the reconstructed phase is only dependent of the total number of photons used to
      generate the phase image and the visibility of the experimental setup. These
      results could be evaluated in measurements as well as in simulations.
      Furthermore, the correlation between absorption and dark-field image was
      calculated. CONCLUSIONS: These results provide the understanding of the noise
      characteristics of grating-based phase-contrast imaging and will help to improve
      image quality.

PMID- 21859015
TI  - The management of tumor motions in the stereotactic irradiation to lung cancer
      under the use of Abches to control active breathing.
AB  - PURPOSE: Breathing control is crucial to ensuring the accuracy of stereotactic
      irradiation for lung cancer. This study monitored respiration in patients with
      inoperable nonsmall-cell lung cancer using a respiration-monitoring apparatus,
      Abches, and investigated the reproducibility of tumor position in these patients.
      METHODS: Subjects comprised 32 patients with nonsmall-cell lung cancer who were
      administered stereotactic radiotherapy under breath-holding conditions monitored
      by Abches. Computed tomography (CT) was performed under breath-holding conditions
      using Abches (Abches scan) for treatment planning. A free-breathing scan was
      performed to determine the range of tumor motions in a given position. After the
      free-breathing scan, Abches scan was repeated and the tumor position thus defined
      was taken as the intrafraction tumor position. Abches scan was also performed
      just before treatment, and the tumor position thus defined was taken as the
      interfraction tumor position. To calculate the errors, tumor positions were
      compared based on Abches scan for the initial treatment plan. The error in tumor
      position was measured using the BrainSCAN treatment-planning device, then
      compared for each lung lobe. RESULTS: Displacements in tumor position were
      calculated in three dimensions (i.e., superior-inferior (S-I), left-right (L-R),
      and anterior-posterior (A-P) dimensions) and recorded as absolute values. For the
      whole lung, average intrafraction tumor displacement was 1.1 mm (L-R), 1.9 mm (A
      P), and 2.0 mm (S-I); the average interfraction tumor displacement was 1.1 mm (L
      R), 2.1 mm (A-P), and 2.0 mm (S-I); and the average free-breathing tumor
      displacement was 2.3 mm (L-R), 3.5 mm (A-P), and 7.9 mm (S-I). The difference
      between using Abches and free breathing could be reduced from approximately 20 mm
      at the maximum to approximately 3 mm in the S-I direction for both intrafraction
      and interfraction positions in the lower lobe. In addition, maximum intrafraction
      tumor displacement with the use of Abches was 4.5 mm (S-I) in the lingular
      segment. These results suggest that use of the Abches system can reduce
      deviations in tumor position to levels below those achieved under free breathing,
      irrespective of the tumor location. CONCLUSIONS: Respiratory control with high
      accuracy and reproducibility is required for high-precision radiotherapy of
      inoperable nonsmall-cell lung cancer and was achieved using Abches in this study.

PMID- 21859016
TI  - The invariance of the total direct DNA strand break yield.
AB  - PURPOSE: The invariance of the total direct strand break yield when DNA is
      irradiated by different types of particles and energies has been reported by
      previous works. This study is intended to explain the physical causes of this
      behavior. METHODS: The GEANT4-DNA extension of the GEANT4 general purpose Monte
      Carlo simulation toolkit has been used to determine direct strand break yields
      induced by protons and alpha particles impacting on a B-DNA geometrical model,
      including five organization levels of the human genetic material. The linear
      energy transfer (LET) of such particles ranges from 4.8 keV/microm (10 MeV
      protons) to about 235 keV/microm (2 MeV alpha particles), at 5.225 pm depth (near
      the center of the region of interest). Direct total, single and double strand
      break probabilities have been determined in a liquid water homogeneous medium
      with a 1.06 g/cm3 density. The energetic spectra of single strand breaks (SSB),
      the number of energy deposition events, and the SSB/event ratio were determined.
      RESULTS: The target-hit probability was found to be independent of both the type
      and the energy of the incident particle, even if this latter is a secondary
      electron. This probability is determined by the geometrical properties of the
      system. The total strand break yield and the number of energy deposition events
      required to reach a certain absorbed dose were found nearly independent of the
      type and energy of the incident ion (proton or alpha). In contrast, the double
      strand break (DSB) yield was found strongly dependent on the LET of the incident
      radiation. CONCLUSIONS: The SSB generation process is homogeneous and independent
      of the LET of the particles involved, at least within the proton and alpha
      particle energy range here studied. The target-hit probability is only determined
      by the ratio between the total volume occupied by targets and that of the ROI
      where the radiation deposits its energy. The maximum separation distance between
      two adjacent SSBs to produce a DSB is the parameter that breaks the homogeneity
      of the target-hit process, making the DSB production process strongly
      heterogeneous.

PMID- 21859017
TI  - Assessment of scatter for the micro-CT subsystem of the trimodality FLEX Triumph
      preclinical scanner.
AB  - PURPOSE: This work aims at assessing, through experimental measurements and Monte
      Carlo calculations, the scatter to primary ratio (SPR) for the micro-CT subsystem
      of the FLEX Triumph preclinical PET-CT scanner to improve its quantitative
      capabilities. METHODS: Experimental measurements were carried out using the
      single blocker method, where five cylindrical blockers with diameters ranging
      between 3 and 11.65 mm were used to assess the SPR without the blocker through
      interpolation. Because of the vertical layout of the imaging device, the blocker
      was placed over rat-sized and mouse-sized phantoms and central and peripheral SPR
      values were obtained by rotating the source and detector. The influence of beam
      energy (30, 50, and 80 kVp), geometrical magnification (1.3 and 2.0) and phantom
      diameter (25 and 50 mm) and density (polyethylene and water) were investigated.
      Monte Carlo (MC) simulations using the MCNP4C code were also performed and
      compared to experimental results to validate their accuracy. RESULTS: The highest
      difference was found in the extreme peripheral region of the small phantom, while
      the maximum difference at the center of the phantom is about 6%, indicating that
      MC simulations can reproduce well the experimental results, at least in the
      region inside the phantom. The maximal SPR (0.562) was obtained for the large
      phantom at 30 kVp and a magnification of 1.3. The full SPR profile was calculated
      using MC simulations and used to express its dependency on beam energy
      (quadratic), air gap (asymptotic), and phantom diameter (quadratic). CONCLUSIONS:
      The obtained results are in good agreement with theoretical predictions. MC
      simulations were valuable for the evaluation of the influence of various
      acquisition parameters on the SPR estimates.

PMID- 21859018
TI  - Experimental comparison of seven commercial dosimetry diodes for measurement of
      stereotactic radiosurgery cone factors.
AB  - PURPOSE: The purpose of this work is to assess the variation in performance of
      various commercially available dosimetry diodes for quantitative small field
      dosimetry, specifically by intercomparing measurements of SRS cone factors.
      METHODS: Measurements were made in 6 MV photon beams with fixed SRS cones for two
      accelerator-based SRS systems: a Varian Clinac iX (Varian/Zmed cones) at 600
      MU/min and a CyberKnife model G4 at 800 MU/min. Measurements were made at 1.5 cm
      depth in water using the IBA Dosimetry "blue phantom" 3D scanning system,
      controlled by OMNIPRO-ACCEPT software. Source-to-detector distance was 100 cm for
      the Clinac, 80 cm for the CyberKnife. Two normalization methods were used for the
      Clinac, one directly referenced to diode measurements in a 10 cm x 10 cm square
      field and the other indirectly by "daisy-chaining" diode measurements to ion
      chamber measurement in the 10 cm x 10 cm reference field through an intermediate
      4 cm x 4 cm square field. CyberKnife factors were referenced directly to
      measurements in the 60 mm reference field. Seven commercial diodes were
      evaluated: PTW TN60008, TN60012, TN60016, TN60017; IBA Dosimetry SFD; Sun Nuclear
      EDGE; Exradin SD1 (first generation prototype). RESULTS: With the exception of
      the SFD, all the evaluated devices yielded surprisingly consistent results.
      Standard deviations of Clinac factors for four diodes (SD1, EDGE, TN60008, and
      TN60012) ranged from approximately 0.50% at 30 mm to 2.0% at 5 mm cones size when
      referenced directly to the 10 cm x 10 cm measurement. The daisy-chaining strategy
      reduced the standard deviation to approximately 0.30% at 30 mm and 1.9% at 5 mm.
      Standard deviations for the same four diodes in the CyberKnife beam ranged up to
      approximately 1.0% at 5 mm. CONCLUSIONS: The inter-detector variation is small
      and appears to be systematic with detector packaging, more inherent filtration
      producing flatter curves for both the relatively hard Clinac beam and the softer
      CyberKnife beam. The daisy-chain strategy appears to be of limited value for most
      of the diodes, but does bring the SFD results into significantly better agreement
      with the others.

PMID- 21859019
TI  - A study of the effect of in-line and perpendicular magnetic fields on beam
      characteristics of electron guns in medical linear accelerators.
AB  - PURPOSE: Using magnetic resonance imaging (MRI) for real-time guidance during
      radiotherapy is an active area of research and development. One aspect of the
      problem is the influence of the MRI scanner, modeled here as an external magnetic
      field, on the medical linear accelerator (linac) components. The present work
      characterizes the behavior of two medical linac electron guns with external
      magnetic fields for in-line and perpendicular orientations of the linac with
      respect to the MRI scanner. METHODS: Two electron guns, Litton L-2087 and Varian
      VTC6364, are considered as representative models for this study. Emphasis was
      placed on the in-line design approach in which case the MRI scanner and the linac
      axes of symmetry coincide and assumes no magnetic shielding of the linac. For the
      in-line case, the magnetic field from a 0.5 T open MRI (GE Signa SP) magnet with
      a 60 cm gap between its poles was computed and used in full three dimensional
      (3D) space charge simulations, whereas for the perpendicular case the magnetic
      field was constant. RESULTS: For the in-line configuration, it is shown that the
      electron beam is not deflected from the axis of symmetry of the gun and the
      primary beam current does not vanish even at very high values of the magnetic
      field, e.g., 0.16 T. As the field strength increases, the primary beam current
      has an initial plateau of constant value after which its value decreases to a
      minimum corresponding to a field strength of approximately 0.06 T. After the
      minimum is reached, the current starts to increase slowly. For the case when the
      beam current computation is performed at the beam waist position the initial
      plateau ends at 0.016 T for Litton L-2087 and at 0.012 T for Varian VTC6364. The
      minimum value of the primary beam current is 27.5% of the initial value for
      Litton L-2087 and 22.9% of the initial value for Varian VTC6364. The minimum
      current is reached at 0.06 and 0.062 T for Litton L-2087 and Varian VTC6364,
      respectively. At 0.16 T the beam current increases to 40.2 and 31.4% from the
      original value of the current for Litton L-2087 and Varian VTC6364, respectively.
      In contrast, for the case when the electron gun is perpendicular to the magnetic
      field, the electron beam is deflected from the axis of symmetry even at small
      values of the magnetic field. As the strength of the magnetic field increases, so
      does the beam deflection, leading to a sharp decrease of the primary beam current
      which vanishes at about 0.007 T for Litton L-2087 and at 0.006 T for Varian
      VTC6364, respectively. At zero external field, the beam rms emittance computed at
      beam waist is 1.54 and 1.29n-mm-mrad for Litton L-2087 and Varian VTC6364,
      respectively. For the inline configuration, there are two particular values of
      the external field where the beam rms emittance reaches a minimum. Litton L-2087
      rms emittance reaches a minimum of 0.72n and 2.01 n-mm-mrad at 0.026 and 0.132 T,
      respectively. Varian VTC6364 rms emittance reaches a minimum of 0.34n and 0.35n
      mm-mrad at 0.028 and 0.14 T, respectively. Beam radius dependence on the external
      field is shown for the in-line configuration for both electron guns. CONCLUSIONS:
      3D space charge simulation of two electron guns, Litton L-2087 and Varian
      VTC6364, were performed for in-line and perpendicular external magnetic fields. A
      consistent behavior of Pierce guns in external magnetic fields was proven. For
      the in-line configuration, the primary beam current does not vanish but a large
      reduction of beam current (up to 77.1%) is observed at higher field strengths;
      the beam directionality remains unchanged. It was shown that for a perpendicular
      configuration the current vanishes due to beam bending under the action of the
      Lorentz force. For in-line configuration it was determined that the rms beam
      emittance reaches two minima for relatively high values of the external magnetic
      field.

PMID- 21859020
TI  - A template-based approach to semi-quantitative SPECT myocardial perfusion
      imaging: Independent of normal databases.
AB  - PURPOSE: Normal patient databases (NPDs) are used to distinguish between normal
      and abnormal perfusion in SPECT myocardial perfusion imaging (MPI) and have
      gained wide acceptance in the clinical environment, yet there are limitations to
      this approach. This study introduces a template-based method for semi
      quantitative MPI, which attempts to overcome some of the NPD limitations.
      METHODS: Our approach involves the construction of a 3D digital healthy heart
      template from the delineation of the patient's left ventricle in the SPECT image.
      This patient-specific template of the heart, filled with uniform activity, is
      then analytically projected and reconstructed using the same algorithm as the
      original image. Subsequent to generating bulls-eye maps for the patient image
      (PB) and the template image (TB), a ratio (PB/TB) is calculated, which produces a
      reconstruction-artifact corrected image (CB). Finally, a threshold is used to
      define defects within CB enabling measurements of the perfusion defect extent
      (EXT). The SPECT-based template (Ts) measurements were compared to those of a CT
      based "ideal" template (TI). Twenty digital phantoms were simulated: male and
      female, each with one healthy heart and nine hearts with various defects. Four
      physical phantom studies were performed modeling a healthy heart and three hearts
      with different defects. The phantom represented a thorax with spine, lung, and
      left ventricle inserts. Images were acquired on General Electric's (GE) Infinia
      Hawkeye SPECT/CT camera using standard clinical MPI protocol. Finally, our method
      was applied to 14 patient MPI rest/stress studies acquired on the GE Infinia
      Hawkeye SPECT/CT camera and compared to the results obtained from Cedars-Sinai's
      QPS software. RESULT: In the simulation studies, the true EXT correlated well
      with the TI (slope= 1.08; offset = -0.40%; r = 0.99) and Ts (slope = 0.90; offset
      = 0.27%; r = 0.99) methods with no significant differences between them.
      Similarly, strong correlations were measured for EXT obtained from QPS and the
      template method for patient studies (slope =0.91; offset = 0.45%; r = 0.98). Mean
      errors in extent for the Ts method using simulation, physical phantom, and
      patient data were 2.7% +/- 2.4%, 0.9% +/- 0.5%, 2.0% +/- 2.7%, respectively.
      CONCLUSIONS: The authors introduced a method for semi-quantitative SPECT MPI,
      which offers a patient-specific approach to define the perfusion defect regions
      within the heart, as opposed to the patient-averaged NPD methodology.

PMID- 21859021
TI  - Reference air kerma and kerma-area product as estimators of peak skin dose for
      fluoroscopically guided interventions.
AB  - PURPOSE: To determine more accurate regression formulas for estimating peak skin
      dose (PSD) from reference air kerma (RAK) or kerma-area product (KAP). METHODS:
      After grouping of the data from 21 procedures into 13 clinically similar groups,
      assessments were made of optimal clustering using the Bayesian information
      criterion to obtain the optimal linear regressions of (log-transformed) PSD vs
      RAK, PSD vs KAP, and PSD vs RAK and KAP. RESULTS: Three clusters of clinical
      groups were optimal in regression of PSD vs RAK, seven clusters of clinical
      groups were optimal in regression of PSD vs KAP, and six clusters of clinical
      groups were optimal in regression of PSD vs RAK and K AP. Prediction of PSD using
      both RAK andKAP is significantly better than prediction of PSD with either RAK or
      KAP alone. The regression of PSD vs RAK provided better predictions of PSD than
      the regression of PSD vs KAP. The partial-pooling (clustered) method yields
      smaller mean squared errors compared with the complete-pooling method.
      CONCLUSION: PSD distributions for interventional radiology procedures are log
      normal. Estimates of PSD derived from RAK and KAP jointly are mos t accurate,
      followed closely byestimates derived from RAK alone. Estimates of PSD derived
      from KAP alone are the least accurate. Using a stochastic search approach, it is
      possible to cluster together certain dissimilar types of procedures to minimize
      the total error sum of squares.

PMID- 21859022
TI  - A Bayesian approach to real-time 3D tumor localization via monoscopic x-ray
      imaging during treatment delivery.
AB  - PURPOSE: Monoscopic x-ray imaging with on-board kV devices is an attractive
      approach for real-time image guidance in modern radiation therapy such as VMAT or
      IMRT, but it falls short in providing reliable information along the direction of
      imaging x-ray. By effectively taking consideration of projection data at prior
      times and/or angles through a Bayesian formalism, the authors develop an
      algorithm for real-time and full 3D tumor localization with a single x-ray imager
      during treatment delivery. METHODS: First, a prior probability density function
      is constructed using the 2D tumor locations on the projection images acquired
      during patient setup. Whenever an x-ray image is acquired during the treatment
      delivery, the corresponding 2D tumor location on the imager is used to update the
      likelihood function. The unresolved third dimension is obtained by maximizing the
      posterior probability distribution. The algorithm can also be used in a
      retrospective fashion when all the projection images during the treatment
      delivery are used for 3D localization purposes. The algorithm does not involve
      complex optimization of any model parameter and therefore can be used in a "plug
      and-play" fashion. The authors validated the algorithm using (1) simulated 3D
      linear and elliptic motion and (2) 3D tumor motion trajectories of a lung and a
      pancreas patient reproduced by a physical phantom. Continuous kV images were
      acquired over a full gantry rotation with the Varian TrueBeam on-board imaging
      system. Three scenarios were considered: fluoroscopic setup, cone beam CT setup,
      and retrospective analysis. RESULTS: For the simulation study, the RMS 3D
      localization error is 1.2 and 2.4 mm for the linear and elliptic motions,
      respectively. For the phantom experiments, the 3D localization error is < 1 mm on
      average and < 1.5 mm at 95th percentile in the lung and pancreas cases for all
      three scenarios. The difference in 3D localization error for different scenarios
      is small and is not statistically significant. CONCLUSIONS: The proposed
      algorithm eliminates the need for any population based model parameters in
      monoscopic image guided radiotherapy and allows accurate and real-time 3D tumor
      localization on current standard LINACs with a single x-ray imager.

PMID- 21859023
TI  - Control of intravascular catheters using an array of active steering coils.
AB  - PURPOSE: To extend the concept of deflecting the tip of a catheter with the
      magnetic force created in an MRI system through the use of an array of
      independently controllable steering coils located in the catheter tip, and to
      present methods for visualization of the catheter and/or surrounding areas while
      the catheter is deflected. METHODS: An array of steering coils made of 42-gauge
      wire was built over a 2.5 Fr (0.83 mm) fiber braided microcatheter. Two of the
      coils were 70 turn axial coils separated by 1 cm, and the third was a 15-turn
      square side coil that was 2 x 4 mm2. Each coil was driven independently by a
      pulse width modulation (PWM) current source controlled by a microprocessor that
      received commands from a MATLAB routine that dynamically set current amplitude
      and direction for each coil. The catheter was immersed in a water phantom
      containing 1% Gd-DTPA that was placed at the isocenter of a 1.5 T MRI scanner.
      Deflections of the catheter tip were measured from image-based data obtained with
      a real-time radio frequency (RF) spoiled gradient echo sequence (GRE). The small
      local magnetic fields generated by the steering coils were exploited to generate
      a hyperintense signal at the catheter tip by using a modified GRE sequence that
      did not include slice-select rewinding gradients. Imaging and excitation modes
      were implemented by synchronizing the excitation of the steering coil array with
      the scanner by ensuring that no current was driven through the coils during the
      data acquisition window; this allowed visualization of the surrounding tissue
      while not affecting the desired catheter position. RESULTS: Deflections as large
      as 2.5 cm were measured when exciting the steering coils sequentially with a 100
      mA maximum current per coil. When exciting a single axial coil, the deflection
      was half this value with 30% higher current. A hyperintense catheter tip useful
      for catheter tracking was obtained by imaging with the modified GRE sequence.
      Clear visualization of the areas surrounding the catheter was obtained by using
      the excitation and imaging mode even with a repetition time (TR) as small as 10
      ms. CONCLUSIONS: A new system for catheter steering is presented that allows
      large deflections through the use of an integrated array of steering coils.
      Additionally, two imaging techniques for tracking the catheter tip and
      visualization of surrounding areas, without interference from the active
      catheter, were shown. Together the demonstrated steerable catheter, control
      system and the imaging techniques will ultimately contribute to the development
      of a steerable system for interventional MRI procedures.

PMID- 21859024
TI  - Dosimetric and mechanical characteristics of a commercial dynamic microMLC used
      in SRS.
AB  - PURPOSE: The aim of this work is to carry out mechanical and dosimetric
      assessments on a commercial dynamic micromulti leaf collimator system to be used
      for stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT).
      Mechanical parameters such as leaf position accuracy with different gantry angles
      and leaf position reproducibility were measured. Also dosimetric measurements of
      the interleaf leakage, intraleaf transmission, penumbra width, and light field
      alignment were carried out. Furthermore, measurements of output factors (Sep) and
      in-air factors (Se) for the microMLC system will be reported. METHODS: EBT2 films
      were used to assess the leaf position error with gantry angle and after stress
      test, penumbra width and light field alignment. Leaf leakage was quantified using
      both EBT2 film and a pinpoint ion chamber. With regard to output factors, the
      pinpoint chamber was placed in a water phantom at 10 cm depth and 100 cm SSD. For
      in-air output factor measurements, 0.2 cm of brass was placed above the photon
      diode as build-up. RESULTS: Measurements of mechanical parameters gave values of
      0.05 cm (SD 0.035) for the average leaf position accuracy for different gantry
      angles and after stress test. Dosimetric measurements, yielded values of 0.22 +/-
      0.01 and 0.24 +/- 0.01 cm, respectively, for side and head leaf penumbras. Also,
      average leaf abutting, leakage and transmission were found to be 0.65, 0.91, and
      0.20%, respectively. CONCLUSIONS: (a) The add-on microMLC system in combination
      with our LINAC has been commissioned to be used for clinical purposes and showed
      good agreement with published results for different ,MLC types. (b) This work has
      lead to the recommendation that leaves should be recalibrated after ten static
      beams or after each dynamic arc.

PMID- 21859025
TI  - Dual-slot antennas for microwave tissue heating: parametric design analysis and
      experimental validation.
AB  - PURPOSE: Design and validate an efficient dual-slot coaxial microwave ablation
      antenna that produces an approximately spherical heating pattern to match the
      shape of most abdominal and pulmonary tumor targets. METHODS: A dual-slot antenna
      geometry was utilized for this study. Permutations of the antenna geometry using
      proximal and distal slot widths from 1 to 10 mm separated by 1-20 mm were
      analyzed using finite-element electromagnetic simulations. From this series, the
      most optimal antenna geometry was selected using a two-term sigmoidal objective
      function to minimize antenna reflection coefficient and maximize the diameter-to
      length aspect ratio of heat generation. Sensitivities to variations in tissue
      properties and insertion depth were also evaluated in numerical models. The most
      optimal dual-slot geometry of the parametric analysis was then fabricated from
      semirigid coaxial cable. Antenna reflection coefficients at various insertion
      depths were recorded in ex vivo bovine livers and compared to numerical results.
      Ablation zones were then created by applying 50 W for 2-10 min in simulations and
      ex vivo livers. Mean zone diameter, length, aspect ratio, and reflection
      coefficients before and after heating were then compared to a conventional
      monopole antenna using ANOVA with post-hoc t-tests. Statistical significance was
      indicated for P <0.05. RESULTS: Antenna performance was highly sensitive to dual
      slot geometry. The best-performing designs utilized a proximal slot width of 1
      mm, distal slot width of 4 mm +/- 1 mm and separation of 8 mm +/- 1 mm. These
      designs were characterized by an active choking mechanism that focused heating to
      the distal tip of the antenna. A dual-band resonance was observed in the most
      optimal design, with a minimum reflection coefficient of -20.9 dB at 2.45 and
      1.25 GHz. Total operating bandwidth was greater than 1 GHz, but the desired
      heating pattern was achieved only near 2.45 GHz. As a result, antenna performance
      was robust to changes in insertion depth and variations in relative permittivity
      of the surrounding tissue medium. In both simulations and ex vivo liver, the dual
      slot antenna created ablations greater in diameter than a coaxial monopole (35 mm
      +/- 2 mm versus 31 mm +/- 2 mm; P<0.05), while also shorter in length (49 mm +/-
      2 mm versus 60 mm +/- 6 mm; P < 0.001) after 10 min. Similar results were
      obtained after 2 and 5 min as well. CONCLUSIONS: Dual-slot antennas can produce
      more spherical ablation zones while retaining low reflection coefficients. These
      benefits are obtained without adding to the antenna diameter. Further evaluation
      for clinical microwave ablation appears warranted.

PMID- 21859026
TI  - Zone-based analysis for automated detection of abnormalities in chest
      radiographs.
AB  - PURPOSE: The aim of this study was to develop an automated method for detection
      of local texture-based and density-based abnormalities in chest radiographs.
      METHODS: The method was based on profile analysis to detect abnormalities in
      chest radiographs. In the method, one density-based feature, Density Symmetry
      Index, and two texture-based features, Roughness Maximum Index and Roughness
      Symmetry Index, were used to detect abnormalities in the lung fields. In each
      chest radiograph, the lung fields were divided into four zones initially and then
      the method was applied to each zone separately. For each zone, Density Symmetry
      Index was obtained from the projection profile of each zone, and Roughness
      Maximum Index and Roughness Symmetry Index were obtained by measuring the
      roughness of the horizontal profiles via moving average technique. Linear
      discriminant analysis was used to classify normal and abnormal cases based on the
      three indices. The discriminant performance of the method was evaluated using ROC
      analysis. RESULTS: The method was evaluated on a database of 250 normal and 250
      abnormal chest images. In the optimized conditions, the zone-based performance Az
      of the method for zones 1, 2, 3, and 4 were 0.917, 0.897, 0.892, and 0.814,
      respectively, and the case-based performance Az of the method was 0.842. Our
      previous method for detection of gross abnormalities was also evaluated on the
      same database. The case-based performance of our previous method was 0.689.
      CONCLUSIONS: In comparing the previous method and the new method proposed in this
      study, there was a great improvement by the new method for detection of local
      texture-based and density-based abnormalities. The new method combined with the
      previous one has potential for screening abnormalities in chest radiographs.

PMID- 21859027
TI  - Analytical equations for CT dose profiles derived using a scatter kernel of Monte
      Carlo parentage with broad applicability to CT dosimetry problems.
AB  - PURPOSE: Knowledge of the complete axial dose profile f(z), including its long
      scatter tails, provides the most complete (and flexible) description of the
      accumulated dose in CT scanning. The CTDI paradigm (including CTDIvol) requires
      shift-invariance along z (identical dose profiles spaced Sat equal intervals),
      and is therefore inapplicable to many of the new and complex shift-variant scan
      protocols, e.g., high dose perfusion studies using variable (or zero) pitch. In
      this work, a convolustion-based beam model developed by Dixon et al. [Med. Phys.
      32, 3712-3728, (2005)] updated with a scatter LSF kernel (or DSF) derived from a
      Monte Carlo simulation by Boone [Med. Phys. 36, 4547-4554 (2009)] is used to
      create an analytical equation for the axial dose profile f(z) in a cylindrical
      phantom. Using f(z), equations are derived which provide the analytical
      description of Sconventional (axial and helical) dose, demonstrating its physical
      underpinnings; and likewise for the peak axial dose f(0) appropriate to
      stationary phantom cone beam CT, (SCBCT). The methodology can also be applied to
      dose calculations in shift-variant scan protocols. This paper is an extension of
      our recent work Dixon and Boone [Med. Phys. 37, 2703-2718 (2010)], which dealt
      only with the properties of the peak dose f(0), its relationship to CTDI, and its
      appropriateness to SCBCT. METHODS: The experimental beam profile data f(z) of
      Mori et al. [Med. Phys. 32, 1061-1069 (2005)] from a 256 channel prototype cone
      beam scanner for beam widths (apertures) ranging from a = 28 to 138 mm are used
      to corroborate the theoretical axial profiles in a 32 cm PMMA body phantom.
      RESULTS: The theoretical functions f(z) closely-matched the central axis
      experimental profile data for all apertures (a = 28 -138 mm). Integration of f(z)
      likewise yields analytical equations for all the (CTDI-based) dosimetric
      quantities of conventional CT (including CTDIL itself) in addition to the peak
      dose f(0) relevant to SCBCT (allowing direct cross-comparison between CT scan
      modes and mathematical proofs of several hypotheses of practical utility in CT
      dosimetry). A fast, analytical dose simulator6 is also demonstrated-successfully
      matching complex dose distributions measured using OSL and film dosimetry.
      CONCLUSIONS: The model described allows one to obtain analytical functions
      describing both the primary and scatter components of the axial dose profile.
      This model (using no empirical functions or adjustable fit parameters) provides a
      good match to the experimental data, as well as a complete analytical description
      of dose for both conventional (axial and helical) CT and cone beam CT. An
      efficient method whereby the complete data set for both modalities can be
      obtained from a single measurement of either CTDI100 or f(0) is illustrated. This
      method is also flexible--allowing calculation of heretofore unattainable doses
      for recently-introduced shift-variant protocols [e.g., variable pitch (irregular
      scan spacing), variable aperture, shuttle mode acquisition, and mA modulation
      schemes].

PMID- 21859028
TI  - Pulse pileup statistics for energy discriminating photon counting x-ray
      detectors.
AB  - PURPOSE: Energy discriminating photon counting x-ray detectors can be subject to
      a wide range of flux rates if applied in clinical settings. Even when the
      incident rate is a small fraction of the detector's maximum periodic rate No,
      pulse pileup leads to count rate losses and spectral distortion. Although the
      deterministic effects can be corrected, the detrimental effect of pileup on image
      noise is not well understood and may limit the performance of photon counting
      systems. Therefore, the authors devise a method to determine the detector count
      statistics and imaging performance. METHODS: The detector count statistics are
      derived analytically for an idealized pileup model with delta pulses of a
      nonparalyzable detector. These statistics are then used to compute the
      performance (e.g., contrast-to-noise ratio) for both single material and material
      decomposition contrast detection tasks via the Cramdr-Rao lower bound (CRLB) as a
      function of the detector input count rate. With more realistic unipolar and
      bipolar pulse pileup models of a nonparalyzable detector, the imaging task
      performance is determined by Monte Carlo simulations and also approximated by a
      multinomial method based solely on the mean detected output spectrum. Photon
      counting performance at different count rates is compared with ideal energy
      integration, which is unaffected by count rate. RESULTS: The authors found that
      an ideal photon counting detector with perfect energy resolution outperforms
      energy integration for our contrast detection tasks, but when the input count
      rate exceeds 20% N0, many of these benefits disappear. The benefit with iodine
      contrast falls rapidly with increased count rate while water contrast is not as
      sensitive to count rates. The performance with a delta pulse model is
      overoptimistic when compared to the more realistic bipolar pulse model. The
      multinomial approximation predicts imaging performance very close to the
      prediction from Monte Carlo simulations. The monoenergetic image with maximum
      contrast-to-noise ratio from dual energy imaging with ideal photon counting is
      only slightly better than with dual kVp energy integration, and with a bipolar
      pulse model, energy integration outperforms photon counting for this particular
      metric because of the count rate losses. However, the material resolving
      capability of photon counting can be superior to energy integration with dual kVp
      even in the presence of pileup because of the energy information available to
      photon counting. CONCLUSIONS: A computationally efficient multinomial
      approximation of the count statistics that is based on the mean output spectrum
      can accurately predict imaging performance. This enables photon counting system
      designers to directly relate the effect of pileup to its impact on imaging
      statistics and how to best take advantage of the benefits of energy
      discriminating photon counting detectors, such as material separation with
      spectral imaging.

PMID- 21859029
TI  - Improved computer-aided detection of small polyps in CT colonography using
      interpolation for curvature estimation.
AB  - PURPOSE: Surface curvatures are important geometric features for the computer
      aided analysis and detection of polyps in CT colonography (CTC). However, the
      general kernel approach for curvature computation can yield erroneous results for
      small polyps and for polyps that lie on haustral folds. Those erroneous
      curvatures will reduce the performance of polyp detection. This paper presents an
      analysis of interpolation's effect on curvature estimation for thin structures
      and its application on computer-aided detection of small polyps in CTC. METHODS:
      The authors demonstrated that a simple technique, image interpolation, can
      improve the accuracy of curvature estimation for thin structures and thus
      significantly improve the sensitivity of small polyp detection in CTC. RESULTS:
      Our experiments showed that the merits of interpolating included more accurate
      curvature values for simulated data, and isolation of polyps near folds for
      clinical data. After testing on a large clinical data set, it was observed that
      sensitivities with linear, quadratic B-spline and cubic B-spline interpolations
      significantly improved the sensitivity for small polyp detection. CONCLUSIONS:
      The image interpolation can improve the accuracy of curvature estimation for thin
      structures and thus improve the computer-aided detection of small polyps in CTC.

PMID- 21859030
TI  - Model-based optoacoustic inversion with arbitrary-shape detectors.
AB  - PURPOSE: Optoacoustic imaging enables mapping the optical absorption of
      biological tissue using optical excitation and acoustic detection. Although most
      image-reconstruction algorithms are based on the assumption of a detector with an
      isotropic sensitivity, the geometry of the detector often leads to a response
      with spatially dependent magnitude and bandwidth. This effect may lead to
      attenuation or distortion in the recorded signal and, consequently, in the
      reconstructed image. METHODS: Herein, an accurate numerical method for simulating
      the spatially dependent response of an arbitrary-shape acoustic transducer is
      presented. The method is based on an analytical solution obtained for a two
      dimensional line detector. The calculated response is incorporated in the forward
      model matrix of an optoacoustic imaging setup using temporal convolution, and
      image reconstruction is performed by inverting the matrix relation. RESULTS: The
      method was numerically and experimentally demonstrated in two dimensions for both
      flat and focused transducers and compared to the spatial-convolution method. In
      forward simulations, the developed method did not suffer from the numerical
      errors exhibited by the spatial-convolution method. In reconstruction simulations
      and experiments, the use of both temporal-convolution and spatial-convolution
      methods lead to an enhancement in resolution compared to a reconstruction with a
      point detector model. However, because of its higher modeling accuracy, the
      temporal-convolution method achieved a noise figure approximated three times
      lower than the spatial-convolution method. CONCLUSIONS: The demonstrated
      performance of the spatial-convolution method shows it is a powerful tool for
      reducing reconstruction artifacts originating from the detector finite size and
      improving the quality of optoacoustic reconstructions. Furthermore, the method
      may be used for assessing new system designs. Specifically, detectors with
      nonstandard shapes may be investigated.

PMID- 21859031
TI  - A general framework and review of scatter correction methods in x-ray cone-beam
      computerized tomography. Part 1: Scatter compensation approaches.
AB  - Since scattered radiation in cone-beam volume CT implies severe degradation of CT
      images by quantification errors, artifacts, and noise increase, scatter
      suppression is one of the main issues related to image quality in CBCT imaging.
      The aim of this review is to structurize the variety of scatter suppression
      methods, to analyze the common structure, and to develop a general framework for
      scatter correction procedures. In general, scatter suppression combines hardware
      techniques of scatter rejection and software methods of scatter correction. The
      authors emphasize that scatter correction procedures consist of the main
      components scatter estimation (by measurement or mathematical modeling) and
      scatter compensation (deterministic or statistical methods). The framework
      comprises most scatter correction approaches and its validity also goes beyond
      transmission CT. Before the advent of cone-beam CT, a lot of papers on scatter
      correction approaches in x-ray radiography, mammography, emission tomography, and
      in Megavolt CT had been published. The opportunity to avail from research in
      those other fields of medical imaging has not yet been sufficiently exploited.
      Therefore additional references are included when ever it seems pertinent.
      Scatter estimation and scatter compensation are typically intertwined in
      iterative procedures. It makes sense to recognize iterative approaches in the
      light of the concept of self-consistency. The importance of incorporating scatter
      compensation approaches into a statistical framework for noise minimization has
      to be underscored. Signal and noise propagation analysis is presented. A main
      result is the preservation of differential-signal-to-noise-ratio (dSNR) in CT
      projection data by ideal scatter correction. The objective of scatter
      compensation methods is the restoration of quantitative accuracy and a balance
      between low-contrast restoration and noise reduction. In a synopsis section, the
      different deterministic and statistical methods are discussed with respect to
      their properties and applications. The current paper is focused on scatter
      compensation algorithms. The multitude of scatter estimation models will be dealt
      with in a separate paper.

PMID- 21859032
TI  - Reflection modeling in ultraviolet phototherapy.
AB  - PURPOSE: Ultraviolet phototherapy is a widely used treatment which has
      exceptional success with a variety of skin conditions. Over-exposure to
      ultraviolet radiation (UVR) can however be detrimental and cause side effects
      such as erythema, photokeratisis, and even skin cancer. Quantifying patient dose
      is therefore imperative to ensure biologically effective treatment while
      minimizing negative repercussions. A dose model for treatment would be valuable
      in achieving these ends. METHODS: Prior work by the authors concentrated on
      modeling the output of the lamps used in treatment and it was found a line source
      model described the output from the sources to a high degree. In practice, these
      lamps are surrounded by reflective anodized aluminum in patient treatment cabins
      and this work extends the model to quantify specular reflections from these
      planes on patient dose. RESULTS: The extension of the model to allow for
      reflected images in addition to tube output shows a remarkably good fit to the
      actual data measured. CONCLUSIONS: The reflection model yields impressive
      accuracy and is a good basis for full UVR cabin modeling.

PMID- 21859033
TI  - Reference-free ground truth metric for metal artifact evaluation in CT images.
AB  - PURPOSE: In computed tomography (CT), metal objects in the region of interest
      introduce data inconsistencies during acquisition. Reconstructing these data
      results in an image with star shaped artifacts induced by the metal
      inconsistencies. To enhance image quality, the influence of the metal objects can
      be reduced by different metal artifact reduction (MAR) strategies. For an
      adequate evaluation of new MAR approaches a ground truth reference data set is
      needed. In technical evaluations, where phantoms can be measured with and without
      metal inserts, ground truth data can easily be obtained by a second reference
      data acquisition. Obviously, this is not possible for clinical data. Here, an
      alternative evaluation method is presented without the need of an additionally
      acquired reference data set. METHODS: The proposed metric is based on an inherent
      ground truth for metal artifacts as well as MAR methods comparison, where no
      reference information in terms of a second acquisition is needed. The method is
      based on the forward projection of a reconstructed image, which is compared to
      the actually measured projection data. RESULTS: The new evaluation technique is
      performed on phantom and on clinical CT data with and without MAR. The metric
      results are then compared with methods using a reference data set as well as an
      expert-based classification. It is shown that the new approach is an adequate
      quantification technique for artifact strength in reconstructed metal or MAR CT
      images. CONCLUSIONS: The presented method works solely on the original projection
      data itself, which yields some advantages compared to distance measures in image
      domain using two data sets. Beside this, no parameters have to be manually
      chosen. The new metric is a useful evaluation alternative when no reference data
      are available.

PMID- 21859034
TI  - Quantitative analysis of beam delivery parameters and treatment process time for
      proton beam therapy.
AB  - PURPOSE: To evaluate patient census, equipment clinical availability, maximum
      daily treatment capacity, use factor for major beam delivery parameters, and
      treatment process time for actual treatments delivered by proton therapy systems.
      METHODS: The authors have been recording all beam delivery parameters, including
      delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and
      couch angles for every treatment field in an electronic medical record system. We
      analyzed delivery system downtimes that had been recorded for every equipment
      failure and associated incidents. These data were used to evaluate the use factor
      of beam delivery parameters, the size of the patient census, and the equipment
      clinical availability of the facility. The duration of each treatment session
      from patient walk-in and to patient walk-out of the treatment room was measured
      for 82 patients with cancers at various sites. RESULTS: The yearly average
      equipment clinical availability in the last 3 yrs (June 2007-August 2010) was
      97%, which exceeded the target of 95%. Approximately 2200 patients had been
      treated as of August 2010. The major disease sites were genitourinary (49%),
      thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams
      have been delivered in approximately 8300 treatment fields. The use factor for
      six beam delivery parameters was also evaluated. Analysis of the treatment
      process times indicated that approximately 80% of this time was spent for patient
      and equipment setup. The other 20% was spent waiting for beam delivery and beam
      on. The total treatment process time can be expressed by a quadratic polynomial
      of the number of fields per session. The maximum daily treatment capacity of our
      facility using the current treatment processes was estimated to be 133 +/- 35
      patients. CONCLUSIONS: This analysis shows that the facility has operated at a
      high performance level and has treated a large number of patients with a variety
      of diseases. The use factor of beam delivery parameters varies by disease site.
      Further improvements in efficiency may be realized in the equipment- and patient
      related processes of treatment.

PMID- 21859035
TI  - 2D/3D fetal cardiac dataset segmentation using a deformable model.
AB  - PURPOSE: To segment the fetal heart in order to facilitate the 3D assessment of
      the cardiac function and structure. METHODS: Ultrasound acquisition typically
      results in drop-out artifacts of the chamber walls. The authors outline a level
      set deformable model to automatically delineate the small fetal cardiac chambers.
      The level set is penalized from growing into an adjacent cardiac compartment
      using a novel collision detection term. The region based model allows
      simultaneous segmentation of all four cardiac chambers from a user defined seed
      point placed in each chamber. RESULTS: The segmented boundaries are automatically
      penalized from intersecting at walls with signal dropout. Root mean square errors
      of the perpendicular distances between the algorithm's delineation and manual
      tracings are within 2 mm which is less than 10% of the length of a typical fetal
      heart. The ejection fractions were determined from the 3D datasets. We validate
      the algorithm using a physical phantom and obtain volumes that are comparable to
      those from physically determined means. The algorithm segments volumes with an
      error of within 13% as determined using a physical phantom. CONCLUSIONS: Our
      original work in fetal cardiac segmentation compares automatic and manual
      tracings to a physical phantom and also measures inter observer variation.

PMID- 21859036
TI  - Modeling diffusion-weighted MRI as a spatially variant gaussian mixture:
      application to image denoising.
AB  - PURPOSE: This work describes a spatially variant mixture model constrained by a
      Markov random field to model high angular resolution diffusion imaging (HARDI)
      data. Mixture models suit HARDI well because the attenuation by diffusion is
      inherently a mixture. The goal is to create a general model that can be used in
      different applications. This study focuses on image denoising and segmentation
      (primarily the former). METHODS: HARDI signal attenuation data are used to train
      a Gaussian mixture model in which the mean vectors and covariance matrices are
      assumed to be independent of spatial locations, whereas the mixture weights are
      allowed to vary at different lattice positions. Spatial smoothness of the data is
      ensured by imposing a Markov random field prior on the mixture weights. The model
      is trained in an unsupervised fashion using the expectation maximization
      algorithm. The number of mixture components is determined using the minimum
      message length criterion from information theory. Once the model has been
      trained, it can be fitted to a noisy diffusion MRI volume by maximizing the
      posterior probability of the underlying noiseless data in a Bayesian framework,
      recovering a denoised version of the image. Moreover, the fitted probability maps
      of the mixture components can be used as features for posterior image
      segmentation. RESULTS: The model-based denoising algorithm proposed here was
      compared on real data with three other approaches that are commonly used in the
      literature: Gaussian filtering, anisotropic diffusion, and Rician-adapted
      nonlocal means. The comparison shows that, at low signal-to-noise ratio, when
      these methods falter, our algorithm considerably outperforms them. When
      tractography is performed on the model-fitted data rather than on the noisy
      measurements, the quality of the output improves substantially. Finally,
      ventricle and caudate nucleus segmentation experiments also show the potential
      usefulness of the mixture probability maps for classification tasks. CONCLUSIONS:
      The presented spatially variant mixture model for diffusion MRI provides
      excellent denoising results at low signal-to-noise ratios. This makes it possible
      to restore data acquired with a fast (i.e., noisy) pulse sequence to acceptable
      noise levels. This is the case in diffusion MRI, where a large number of
      diffusion-weighted volumes have to be acquired under clinical time constraints.

PMID- 21859037
TI  - Parallel fuzzy connected image segmentation on GPU.
AB  - PURPOSE: Image segmentation techniques using fuzzy connectedness (FC) principles
      have shown their effectiveness in segmenting a variety of objects in several
      large applications. However, one challenge in these algorithms has been their
      excessive computational requirements when processing large image datasets.
      Nowadays, commodity graphics hardware provides a highly parallel computing
      environment. In this paper, the authors present a parallel fuzzy connected image
      segmentation algorithm implementation on NVIDIA's compute unified device
      Architecture (CUDA) platform for segmenting medical image data sets. METHODS: In
      the FC algorithm, there are two major computational tasks: (i) computing the
      fuzzy affinity relations and (ii) computing the fuzzy connectedness relations.
      These two tasks are implemented as CUDA kernels and executed on GPU. A dramatic
      improvement in speed for both tasks is achieved as a result. RESULTS: Our
      experiments based on three data sets of small, medium, and large data size
      demonstrate the efficiency of the parallel algorithm, which achieves a speed-up
      factor of 24.4x, 18.1x, and 10.3x, correspondingly, for the three data sets on
      the NVIDIA Tesla C1060 over the implementation of the algorithm on CPU, and takes
      0.25, 0.72, and 15.04 s, correspondingly, for the three data sets. CONCLUSIONS:
      The authors developed a parallel algorithm of the widely used fuzzy connected
      image segmentation method on the NVIDIA GPUs, which are far more cost- and speed
      effective than both cluster of workstations and multiprocessing systems. A near
      interactive speed of segmentation has been achieved, even for the large data set.

PMID- 21859038
TI  - SonoKnife: feasibility of a line-focused ultrasound device for thermal ablation
      therapy.
AB  - PURPOSE: To evaluate the feasibility of line-focused ultrasound for thermal
      ablation of superficially located tumors. METHODS: A SonoKnife is a cylindrical
      section ultrasound transducer designed to radiate from its concave surface. This
      geometry generates a line-focus or acoustic edge. The motivation for this
      approach was the noninvasive thermal ablation of advanced head and neck tumors
      and positive neck nodes in reasonable treatment times. Line-focusing may offer
      advantages over the common point-focusing of spherically curved radiators such as
      faster coverage of a target volume by scanning of the acoustic edge. In this
      paper, The authors report studies using numerical models and phantom and ex vivo
      experiments using a SonoKnife prototype. RESULTS: Acoustic edges were generated
      by cylindrical-section single-element ultrasound transducers numerically, and by
      the prototype experimentally. Numerically, simulations were performed to
      characterize the acoustic edge for basic design parameters: transducer
      dimensions, line-focus depth, frequency, and coupling thickness. The dimensions
      of the acoustic edge as a function of these parameters were determined. In
      addition, a step-scanning simulation produced a large thermal lesion in a
      reasonable treatment time. Experimentally, pressure distributions measured in
      degassed water agreed well with acoustic simulations, and sonication experiments
      in gel phantoms and ex vivo porcine liver samples produced lesions similar to
      those predicted with acoustic and thermal models. CONCLUSIONS: Results support
      the feasibility of noninvasive thermal ablation with a SonoKnife.

PMID- 21859039
TI  - Characterization of imaging performance in differential phase contrast CT
      compared with the conventional CT--noise power spectrum NPS(k).
AB  - PURPOSE: The differential phase contrast CT is emerging as a new technology to
      improve the contrast sensitivity of the conventional CT. Via system analysis,
      modeling, and computer simulation, the authors study the noise power spectrum
      (NPS)--an imaging performance indicator-of the differential phase contrast CT and
      compare it with that of the conventional CT. METHODS: The differential phase
      contrast CT is implemented with x-ray tube and gratings. The x-ray propagation
      and data acquisition are modeled and simulated with Fourier analysis and Fresnel
      analysis. To avoid any interference caused by scatter and beam hardening, a
      monochromatic x-ray source (30 keV) is assumed, which irradiates the object to be
      imaged by 360 degrees so that no weighting scheme is needed. A 20-fold up
      sampling is assumed to simulate x-ray beam's propagation through the gratings Gl
      and G2 with periods 8 and 4 microm, respectively, while the intergrating distance
      is 193.6 mm (1/16 of the Tabolt distance). The dimension of the detector cell for
      data acquisition ranges from 32 x 32 to 128 x 128 microm2, while the field of
      view in data acquisition is 40.96 x 40.96 mm2. A uniform water phantom with a
      diameter 37.68 mm is employed to study the NPS, with its complex refraction
      coefficient n = 1 - delta + ibeta = 1 - 2.5604 x 10(-7) + i1.2353 x 10(-10). The
      x-ray flux ranges from 10(6) to 10(8) photon/cm2.projection and observes the
      Poisson distribution, which is consistent with that of micro-CT in preclinical
      applications. The image matrix of reconstructed water phantom is 1280 x 1280, and
      a total of 180 regions at 128 x 128 matrix are used for NPS calculation via 2D
      Fourier Transform in which adequate zero padding is applied to avoid aliasing.
      RESULTS: The preliminary data show that the differential phase contrast CT
      manifests its NPS with a l/|k| trait, while the distribution of the conventional
      CTs NPS observes |k|. This accounts for the significant difference in their noise
      granularity and the differential phase contrast CTs substantial advantage in
      noise over the conventional CT, particularly, in the situations where the
      detector cell size for data acquisition is smaller than 100 microm. CONCLUSIONS:
      The differential phase contrast CT detects the projection of refractive
      coefficient's derivative and uses the Hilbert filter for image reconstruction,
      which leads to the radical difference in its NPS and the advantage in noise in
      comparison to that of the conventional CT.

PMID- 21859040
TI  - Characteristics of an OSLD in the diagnostic energy range.
AB  - PURPOSE: Optically stimulated luminescence (OSL) dosimetry has been recently
      introduced in radiation therapy as a potential alternative to the
      thermoluminescent dosimeter (TLD) system. The aim of this study was to
      investigate the feasibility of using OSL point dosimeters in the energy range
      used in diagnostic imaging. METHODS: NanoDot OSL dosimeters (OSLDs) were used in
      this study, which started with testing the homogeneity of a new packet of
      nanoDots. Reproducibility and the effect of optical treatment (bleaching) were
      then examined, followed by an investigation of the effect of accumulated dose on
      the OSLD indicated doses. OSLD linearity, angular dependence, and energy
      dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips
      using standard CT dose phantoms at 80 and 120 kVp settings was performed.
      RESULTS: Batch homogeneity showed a coefficient of variation of <5%. Single
      irradiation measurements with bleaching after each OSL readout was found to be
      associated with a 3.3% reproducibility (one standard deviation measured with a 8
      mGy test dose), and no systematic change in OSLDs sensitivity could be noted from
      measurement to measurement. In contrast, the multiple-irradiation readout without
      bleaching in between measurements was found to be associated with an uncertainty
      (using a 6 mGy test dose) that systematically increased with accumulated dose,
      reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray,
      CT, and mammography units with an R2 > 0.99. The angular dependence test showed a
      drop of approximately 70% in the OSLD response at 90 degrees in mammography (25
      kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and
      20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy
      dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and
      1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the
      OSLDs and TLDs showed no significant variation (p > 0.1). CONCLUSIONS: OSLDs
      exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a
      linear response. In addition, they showed no statistically significant difference
      with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the
      dose estimate was found as a result of relatively high accumulated dose.
      Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp
      techniques. Energy dependence of about 60% was found, and correction factors were
      suggested for the range of energies investigated. Therefore, if angular and
      energy dependences are taken into consideration and the uncertainty associated
      with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as
      point dosimeters in diagnostic settings.

PMID- 21859041
TI  - Pulmonary nodule registration: rigid or nonrigid?
AB  - PURPOSE: The primary aim of this study is to investigate the performance
      difference of rigid and nonrigid registration schemes in matching corresponding
      pulmonary nodules depicted on sequential chest computed tomography (CT)
      examinations. METHODS: A gradient descent based rigid registration algorithm with
      scaling was developed and it handled the involved geometric transformations
      (i.e., translation, rescaling, shearing, and rotation) separately instead of
      optimizing them in a single pass. Given two lung CT examinations, the scaling and
      translation parameters were simply estimated from the lung volume dimensions
      (e.g., size and mass center), while the rotation parameters were optimized
      progressively using gradient descent. To investigate the performance difference
      of rigid and nonrigid schemes in pulmonary nodule registration, the well-known
      nonrigid Demons algorithm was implemented and tested along with the developed
      schemes against 60 diverse low-dose clinical lung CT examinations with average 2
      yr follow-up scans. A verified cancer and its correspondence in the follow-up
      scan as well as their spatial locations (mass center) were identified in each
      examination. In addition to the computational efficiency, the accuracy of these
      registration procedures was assessed by computing the Euclidean distances between
      the corresponding nodules after the registration. To demonstrate the advantage of
      the developed algorithm, the authors also implemented a fast iterative closest
      point (ICP) based rigid algorithm and compared their performance. RESULTS: Our
      experiments on the collected chest CT examinations showed that the nodule
      registration errors in 3D Euclidean distance for the developed rigid affine
      approach, the traditional ICP algorithm, and the refining nonrigid Demons
      algorithm were 9.6, 9.8, and 10.0 mm, respectively, and the corresponding
      computational costs in time were 5, 300, and 55 s, respectively. CONCLUSIONS: A
      rigid solution may be preferred in practice for the pulmonary nodule registration
      in longitudinal studies because of its relatively high efficiency and sufficient
      accuracy for the clinical need.

PMID- 21859042
TI  - A quality assurance protocol for diffusion tensor imaging using the head phantom
      from American College of Radiology.
AB  - PURPOSE: To propose a quality assurance procedure for routine clinical diffusion
      tensor imaging (DTI) using the widely available American College of Radiology
      (ACR) head phantom. METHODS: Analysis was performed on the data acquired at 1.5
      and 3.0 T on whole body clinical MRI scanners using the ACR phantom and included
      the following: (1) the signal-to-noise ratio (SNR) at the center and periphery of
      the phantom, (2) image distortion by EPI readout relative to spin echo imaging,
      (3) distortion of high-b images relative to the b= 0 image caused by diffusion
      encoding, and (4) determination of fractional anisotropy (FA) and mean
      diffusivity (MD) measured with region-of-interest (ROI) and pixel-based
      approaches. Reproducibility of the measurements was assessed by five repetitions
      of data acquisition on each scanner. RESULTS: The SNR at the phantom center was
      approximately half of that near the periphery at both 1.5 and 3 T. The image
      distortion by the EPI readout was up to 7 mm at 1.5 T and 10 mm at 3 T. The
      typical distortion caused by eddy currents from diffusion encoding was on the
      order of 0.5 mm. The difference between ROI-based and pixel-based MD
      quantification was 1.4% at 1.5 T and 0.3% at 3 T. The ROI-based MD values were in
      close agreement (within 2%) with the reference values. The ROI-based FA values
      were approximately a factor of 10 smaller than pixel-based values and less than
      0.01. The measurement reproducibility was sufficient for quality assurance (QA)
      purposes. CONCLUSIONS: This QA approach is simple to perform and evaluates key
      aspects of the scanner performance for DTI data acquisition using a widely
      available phantom.

PMID- 21859043
TI  - Gain and offset calibration reduces variation in exposure-dependent SNR among
      systems with identical digital flat-panel detectors.
AB  - PURPOSE: The conditions under which vendor performance criteria for digital
      radiography systems are obtained do not adequately simulate the conditions of
      actual clinical imaging with respect to radiographic technique factors, scatter
      production, and scatter control. Therefore, the relationship between performance
      under ideal conditions and performance in clinical practice remains unclear.
      Using data from a large complement of systems in clinical use, the authors sought
      to develop a method to establish expected performance criteria for digital flat
      panel radiography systems with respect to signal-to-noise ratio (SNR) versus
      detector exposure under clinical conditions for thoracic imaging. METHODS: The
      authors made radiographic exposures of a patient-equivalent chest phantom at 125
      kVp and 180 cm source-to-image distance. The mAs value was modified to produce
      exposures above and below the mAs delivered by automatic exposure control.
      Exposures measured free-in-air were corrected to the imaging plane by the inverse
      square law, by the attenuation factor of the phantom, and by the Bucky factor of
      the grid for the phantom, geometry, and kilovolt peak. SNR was evaluated as the
      ratio of the mean to the standard deviation (SD) of a region of interest
      automatically selected in the center of each unprocessed image. Data were
      acquired from 18 systems, 14 of which were tested both before and after gain and
      offset calibration. SNR as a function of detector exposure was interpolated using
      a double logarithmic function to stratify the data into groups of 0.2, 0.5, 1.0,
      2.0, and 5.0 mR exposure (1.8, 4.5, 9.0, 18, and 45 microGy air KERMA) to the
      detector. RESULTS: The mean SNR at each exposure interval after calibration
      exhibited linear dependence on the mean SNR before calibration (r2=0.9999). The
      dependence was greater than unity (m = 1.101 +/- 0.006), and the difference from
      unity was statistically significant (p <0.005). The SD of mean SNR after
      calibration also exhibited linear dependence on the SD of the mean SNR before
      calibration (r2 = 0.9997). This dependence was less than unity (m = 0.822 +/-
      0.008), and the difference from unity was also statistically significant (p <
      0.005). Systems were separated into two groups: systems with a precalibration SNR
      higher than the median SNR (N = 7), and those with a precalibration SNR lower
      than the median SNR (N= 7). Posthoc analysis was performed to correct for
      expanded false positive results. After calibration, the authors noted differences
      in mean SNR within both high and low groups, but these differences were not
      statistically significant at the 0.05 level. SNR data from four additional
      systems and one system from those previously tested after replacement of its
      detector were compared to the 95% confidence intervals (CI) calculated from the
      postcalibration SNR data. The comparison indicated that four of these five
      systems were consistent with the CI derived from the previously tested 14 systems
      after calibration. Two systems from the paired group that remained outside the CI
      were studied further. One system was remedied with a grid replacement. The
      nonconformant behavior of the other system was corrected by replacing the image
      receptor. CONCLUSIONS: Exposure-dependent SNR measurements under conditions
      simulating thoracic imaging allowed us to develop criteria for digital flat-panel
      imaging systems from a single manufacturer. These measurements were useful in
      identifying systems with discrepant performance, including one with a defective
      grid, one with a defective detector, and one that had not been calibrated for
      gain and offset. The authors also found that the gain and offset calibration
      reduces variation in exposure-dependent SNR performance among the systems.

PMID- 21859044
TI  - Monte Carlo dose enhancement studies in microbeam radiation therapy.
AB  - PURPOSE: A radical radiation therapy treatment for gliomas requires extremely
      high absorbed doses resulting in subsequent deleterious side effects in healthy
      tissue. Microbeam radiation therapy (MRT) is an innovative technique based on the
      fact that normal tissue can withstand high radiation doses in small volumes
      without any significant damage. The synchrotron-generated x-ray beam is
      collimated and delivered to an array of narrow micrometer-sized planar
      rectangular fields. Several preclinical experiments performed at the Brookhaven
      National Laboratory (BNL) and at the European Synchrotron Radiation Facility
      (ESRF) confirmed that MRT yields a higher therapeutic index than nonsegmented
      beams of the same characteristics. This index can be greatly improved by loading
      the tumor with high atomic number (Z) contrast agents. The aim of this work is to
      find the high-Z element that provides optimum dose enhancement. METHODS: Monte
      Carlo simulations (PENELOPE/penEasy) were performed to assess the peak and valley
      doses as well as their ratio (PVDR) in healthy tissue and in the tumor, loaded
      with different contrast agents. The optimization criteria used were maximization
      of the ratio between the PVDR values in healthy tissue respect to the PVDR in the
      tumor and minimization of bone and brain valley doses. RESULTS: Dose enhancement
      factors, PVDR, and valley doses were calculated for different high-Z elements. A
      significant decrease of PVDR values in the tumor, accompanied by a gain in the
      valley doses, was found in the presence of high-Z elements. This enables the
      deposited dose in the healthy tissue to be reduced. The optimum high-Z element
      depends on the irradiation configuration. As a general trend, the best outcome is
      provided by the highest Z contrast agents considered, i.e., gold and thallium.
      However, lanthanides (especially Lu) and hafnium also offer a satisfactory
      performance. CONCLUSIONS: The remarkable therapeutic index in microbeam radiation
      therapy can be further improved by loading the tumor with a high-Z element. This
      study reports quantitative data on several dosimetric magnitudes in order to find
      the optimum contrast agent. Although the final choice of the element will also
      depend on possible cytotoxicity, three elements were found to be worthy of
      mention: gold, thallium, and lutetium.

PMID- 21859045
TI  - Overestimations in zero frequency DQE of x-ray imaging converters assessed by
      Monte Carlo techniques based on the study of energy impartation events.
AB  - PURPOSE: The performance of various x-ray converters, employed in medical imaging
      systems, has been widely examined by several methodologies (experimental,
      analytical, and Monte Carlo techniques). The x-ray converters most frequently
      employed in energy integrating digital radiology detectors are the Gd2O2S:Tb
      granular phosphor, the CsI:TI structured phosphor, and the a-Se photoconductor.
      The imaging characteristics of an x-ray converter are affected by its x-ray
      detection properties. However, various definitions of x-ray detection have been
      used in the literature, leading to different results for the quantum detection
      efficiency (QDE) for the same type of x-ray converter. For this reason, there is
      a need for accurate determination of the x-ray detection and, in particular, its
      relation to detector response. METHODS: The present article reports on the
      performance of the three aforementioned x-ray converters in terms of the QDE and
      the x-ray statistical factor Ix, and examines the effect of the x-ray detection,
      directly related to converter output signal, on the zero-frequency DQE. For the
      purposes of this study, Monte Carlo simulation was used to model the x-ray
      interactions within the x-ray converter. Simulations were carried out in the
      energy range from 10 keV up to 80 keV and considering two layers of different
      coating weights (50 and 100 mg/cm2). The prediction and comparison of zero
      frequency DQE were based on two different approaches for x-ray detection, i.e.,
      (a) fraction of interacting photons and (b) fraction of photons leading to energy
      deposition. In addition, the effect of energy deposition through Compton
      scattering events on the DQE values was estimated. RESULTS: Our results showed
      discrepancies between Monte Carlo techniques (based on energy deposition events)
      and analytical calculations (based on x-ray attenuation) on QDE. Discrepancies
      were found to range up to 10% for Gd2O2S:Tb (100 mg/cm2), 7.7% for CsI:T1 (50
      mg/cm2), and 8.2% for a-Se (50 mg/cm2). Discrepancies were analyzed by examining
      the scattering effects (elastic and inelastic) within the converters and led to
      further analysis of scattering events on Ix, as well. Significant overestimations
      were found for both factors (QDE and I,) on the zero-frequency DQE. CONCLUSIONS:
      Considering that the highest overestimation was found in the thin layer (50
      mg/cm2), Monte Carlo evaluation showed that the overestimation (%) between DQE
      values (based on either x-ray interacting events or energy impartation events)
      was more significant at 20 keV for CsI:T1 (approximately 2.1%), at 40 keV for
      Gd2O2S:Tb (approximately 8.1%), and finally at 60 and 80 keV for a-Se converter
      (approximately 4.8 and 8.2%, respectively). Finally, the overestimation due to
      the effect of Compton scattering on DQE was found more significant for the a-Se
      converter and especially above 40 keV reaching approximately the value of 8.9% at
      80 keV.

PMID- 21859046
TI  - Dosimetric impact of image artifact from a wide-bore CT scanner in radiotherapy
      treatment planning.
AB  - PURPOSE: Traditional computed tomography (CT) units provide a maximum scan field
      of-view (sFOV) diameter of 50 cm and a limited bore size, which cannot
      accommodate a large patient habitus or an extended simulation setup in radiation
      therapy (RT). Wide-bore CT scanners with increased bore size were developed to
      address these needs. Some scanners have the capacity to reconstruct the CT images
      at an extended FOV (eFOV), through data interpolation or extrapolation, using
      projection data acquired with a conventional sFOV. Objects that extend past the
      sFOV for eFOV reconstruction may generate image artifacts resulting from
      truncated projection data; this may distort CT numbers and structure contours in
      the region beyond the sFOV. The purpose of this study was to evaluate the
      dosimetric impact of image artifacts from eFOV reconstruction with a wide-bore CT
      scanner in radiotherapy (RT) treatment planning. METHODS: Testing phantoms (i.e.,
      a mini CT phantom with equivalent tissue inserts, a set of CT normal phantoms and
      anthropomorphic phantoms of the thorax and the pelvis) were used to evaluate eFOV
      artifacts. Reference baseline images of these phantoms were acquired with the
      phantom centrally positioned within the sFOV. For comparison, the phantoms were
      then shifted laterally and scanned partially outside the sFOV, but still within
      the eFOV. Treatment plans were generated for the thoracic and pelvic
      anthropomorphic phantoms utilizing the Eclipse treatment planning system (TPS) to
      study the potential effects of eFOV artifacts on dose calculations. All dose
      calculations of baseline and test treatment plans were carried out using the same
      MU. RESULTS: Results show that both body contour and CT numbers are altered by
      image artifacts in eFOV reconstruction. CT number distortions of up to -356 HU
      for bone tissue and up to 323 HU for lung tissue were observed in the mini CT
      phantom. Results from the large body normal phantom, which is close to a clinical
      patient size, show average CT number changes of up to -49 HU. Wider distribution
      (i.e., standard deviation) of the HU values was seen when the phantom was placed
      at more than 2.8 cm beyond the 50 cm sFOV. Anthropomorphic phantom studies with
      several standard beam configurations show that body contour distortion causes
      tumor dose calculation reduction of 3.0 and 1.9% for 6 and 23 MV x-rays,
      respectively, when not accounting for tissue heterogeneities during dose
      computation. When heterogeneity correction is used in planning, the competing
      effects of the body contour distortion and the CT number distortion cause a
      smaller error in tumor dose calculation. Less than 0.9% error in calculated dose
      was observed in volumetric modulated are therapy (VMAT) treatment plans.
      CONCLUSIONS: The image artifacts from eFOV reconstruction alter the CT numbers
      and body contours of the imaged objects, which has the potential to produce
      inaccuracies in dose calculations during radiotherapy treatment planning. The
      radiation therapy team should be aware of these image artifacts and their effects
      on target dose calculations during CT simulation as well as treatment planning.

PMID- 21859047
TI  - Comment on "IMRT commissioning: some causes for concern".

PMID- 21859048
TI  - "A perfection of means, and confusion of aims": finding the essence of autonomy
      in assisted death laws.

PMID- 21859049
TI  - Incremental health care utilization and expenditures for chronic rhinosinusitis
      in the United States.
AB  - OBJECTIVES: I determined incremental increases in health care expenditures and
      utilization associated with chronic rhinosinusitis (CRS). METHODS: Patients with
      a reported diagnosis of CRS were extracted from the 2007 Medical Expenditure
      Panel Survey medical conditions file and linked to the consolidated expenditures
      file. The patients with CRS were then compared to patients without CRS to
      determine differences in health care utilization (office visits,emergency
      facility visits, and prescriptions filled), as well as differences in health care
      expenditures (total health care costs, office visit costs, prescription
      medication costs, and self-expenditures) by use of demographically adjusted and
      comorbidity-adjusted multivariate models. RESULTS: An estimated 11.1+/-0.48
      million adult patients reported having CRS in 2007 (4.9%+/-0.2% of the US
      population). The additional incremental health care utilizations associated with
      CRS relative to patients without CRS for office visits, emergency facility
      visits, and number of prescriptions filled were 3.45+/-0.42, 0.09+/-0.03, and
      5.5+/-0.8, respectively (all p<or=0.001). Similarly, additional health care
      expenditures associated with CRS for total health care expenses, office-based
      expenditures, prescription expenditures, and self-expenditures were $772+/-$300,
      $346+/-$130, $397+/-$88, and $90+/-$24, respectively (all p<or=0.01).
      CONCLUSIONS: Chronic rhinosinusitis is associated with a substantial incremental
      increase in health care utilization and expenditures due to increases in office
      based and prescription expenditures. The national health care costs of CRS remain
      very high, at an estimated $8.6 billion per year.

PMID- 21859050
TI  - Complications of cochlear implantation in adults.
AB  - OBJECTIVES: We describe our experience of intraoperative and postoperative
      complications of cochlear implantation in an adult population. METHODS: Between
      April 1986 and June 2010, the senior author (A.S.) performed 449 cochlear
      implantations in two different institutions. Of these, 212 implantations were in
      adults. The operative techniques were similar in all cases. RESULTS:
      Complications were observed in 12 of the 212 adult cases (5.7%), of which 10 were
      major (4.7%) and 2 minor (1%). In 7 cases, reimplantation was necessitated by
      device failure (6 cases; 2.8%) or device extrusion (1 case; 0.5%). In 2 elderly
      patients (1%), a minor dural injury with a cerebrospinal fluid leak was
      controlled during the operation with temporalis fascia grafting. In 1 patient
      (0.5%), a subdural hematoma was observed after bipolar cauterization of a
      prominent diploic vein. In 2 subjects (1%), a wound infection was noted soon
      after implantation and was treated successfully on an outpatient basis.
      CONCLUSIONS: Cochlear implantation is generally a safe procedure. The most common
      complication was device failure. Although complications in this adult population
      were rather uncommon, some of them were serious, and an immediate intervention
      was necessary for a successful outcome.

PMID- 21859051
TI  - Melatonin: can it stop the ringing?
AB  - OBJECTIVES: We sought to report the efficacy of oral melatonin as treatment for
      chronic tinnitus and to determine whether particular subsets of tinnitus patients
      have greater benefit from melatonin therapy than others. METHODS: This was a
      prospective, randomized, double-blind, crossover clinical trial in an ambulatory
      tertiary referral otology and neurotology practice. Adults with chronic tinnitus
      were randomized to 3 mg melatonin or placebo nightly for 30 days followed by a 1
      month washout period. Each group then crossed into the opposite treatment arm for
      30 days. The tests audiometric tinnitus matching (TM), Tinnitus Severity Index
      (TSI), Self Rated Tinnitus (SRT), Pittsburgh Sleep Quality Index (PSQI), and Beck
      Depression Inventory (BDI) were administered at the outset and every 30 days
      thereafter to assess the effects of each intervention. RESULTS: A total of 61
      subjects completed the study. A significantly greater decrease in TM and SRT
      scores (p < 0.05) from baseline was observed after treatment with melatonin
      relative to the effect observed with placebo. Male gender, bilateral tinnitus,
      noise exposure, no prior tinnitus treatment, absence of depression and/or anxiety
      at baseline, and greater pretreatment TSI scores were associated with a positive
      response to melatonin. Absence of depression and/or anxiety at baseline, greater
      pretreatment TSI scores, and greater pretreatment SRT scores were found to be
      positively associated with greater likelihood of improvement in both tinnitus and
      sleep with use of melatonin (p<0.05). CONCLUSIONS: Melatonin is associated with a
      statistically significant decrease in tinnitus intensity and improved sleep
      quality in patients with chronic tinnitus. Melatonin is most effective in men,
      those without a history of depression, those who have not undergone prior
      tinnitus treatments, those with more severe and bilateral tinnitus, and those
      with a history of noise exposure.

PMID- 21859052
TI  - Audiology telepractice in a clinical environment: a communication perspective.
AB  - Access to adequate hearing health care is an obstacle that many individuals face
      worldwide. The prospect of providing audiology services via the Internet is an
      attractive and viable alternative to traditional face-to-face interaction between
      patients and audiologists, thus affording improved access to hearing health care
      for traditionally underserved populations. This article details our experience of
      using a web-based system with wireless audiometers and videoconferencing software
      to administer remote audiological assessments in an active medical practice. It
      discusses the technological infrastructure used and the pragmatic issues that
      arise when the Internet, Bluetooth wireless audiometers, and videoconferencing
      devices are converged into a clinical setting. Patients at a local office of
      otolaryngologists were recruited to participate in a study in which remote
      assessment results were compared to those collected from a traditional face-to
      face assessment. Preliminary data demonstrated that the assessment results from
      the two sources were comparable. We conclude that remote hearing assessment over
      the Internet can be achieved through a distributed system synthesized with
      Internet, wireless communication, and videoconferencing technologies, supported
      by appropriate staff.

PMID- 21859053
TI  - Outcomes of conventional amplification for pediatric unilateral hearing loss.
AB  - OBJECTIVES: Although children with unilateral hearing loss (UHL) are at risk for
      educational difficulties and behavioral problems, the research on treatment
      outcomes is limited. Previous studies suggested that children with UHL would
      benefit from frequency-modulated assistive devices only. The objective of this
      study was to examine whether children with UHL would benefit from using a
      conventional hearing aid in the poorer-hearing ear. METHODS: Eight children, 7 to
      12 years of age, with mild to moderately severe UHL and their parents and
      teachers participated in this study. The participants were fitted with digital
      hearing aids by use of pediatric prescriptive targets. The primary outcome
      measures were speech perception tests in quiet and noise and subjective
      assessments from participants, parents, and teachers, administered before hearing
      aid fitting and after 3 months of hearing aid use. RESULTS: The group average
      speech perception scores showed no significant aided benefit or detriment in any
      of the conditions tested. However, subjective assessments showed large
      significant aided benefits at home and school according to the children and their
      parents, and in quality of life as reported by the children with UHL.
      CONCLUSIONS: Overall, the results suggest that a hearing aid trial should be
      considered for children with mild to moderately severe UHL, with individual
      monitoring for benefit.

PMID- 21859054
TI  - Nasal nitric oxide and lifestyle exposure to tobacco smoke.
AB  - OBJECTIVES: Nitric oxide (NO) is a reactive gas generated by inflammatory cells
      and mucosal epithelial cells of the nose and paranasal sinuses and is an
      important mediator in nonspecific host defense against infectious agents.
      However, NO also mediates physiologic events such as vasodilation, mucus
      hypersecretion, and mucosal disruption that are associated with inflammatory
      conditions, and it is a regulator of ciliary beat frequency. In the present
      study, we hypothesized that lifestyle exposure to tobacco smoke, whether through
      active smoking or by inadvertent exposure to secondhand tobacco smoke, would
      result in higher detectable levels of nasal NO (nNO) than are found in well
      documented nonsmokers. METHODS: Nasal NO measurements were obtained concomitant
      with assays of urine cotinine from well-documented nonsmokers, active smokers,
      and individuals exposed by lifestyle to secondhand smoke. These parameters were
      statistically analyzed to determine whether increasing levels of tobacco smoke
      exposure yield higher concentrations of nNO. RESULTS: Our results and subsequent
      statistical analyses imply that active smokers who exhibit high urine cotinine
      levels exhibit significant increases in nNO levels in comparison to both
      nonsmokers and nonsmokers exposed to secondhand smoke. CONCLUSIONS: There is an
      increased level of nNO associated with tobacco smoke exposure that may contribute
      to the inflammatory processes characteristic of disease pathogenesis in smokers.

PMID- 21859055
TI  - Are postural restrictions necessary for management of posterior canal benign
      paroxysmal positional vertigo?
AB  - OBJECTIVES: An important component of management of benign paroxysmal positional
      vertigo (BPPV) has been the application of postural restrictions after use of a
      canalith repositioning maneuver (CRM) to prevent the return of otolithic debris
      into the posterior semicircular canal (PSC). This study was designed to explore
      the effectiveness of postural restrictions in patients with BPPV caused by
      otolithic debris in the PSC. METHODS: Seventy-four adult patients with unilateral
      PSC BPPV were enrolled into this study. All patients were managed with a CRM-
      either the modified Epley maneuver or the Semont maneuver. The patients were
      divided randomly into 2 groups: group A, with postural restrictions, and group B,
      without postural restrictions. The statistical analysis was performed with X2
      tests and t-tests. RESULTS: No patients in either group showed positional
      nystagmus in the posttreatment evaluation under infrared videonystagmoscopy. No
      patients had symptoms of vertigo after the therapy. The results of follow-up
      vestibular tests were normal in both groups. CONCLUSIONS: In our experience,
      postural restrictions do not enhance the beneficial effect of the CRMs. They do
      not seem to have any protective role and therefore should not be recommended as
      an adjunct to the treatment of PSC BPPV.

PMID- 21859056
TI  - Spasmodic dysphonia: onset, course, socioemotional effects, and treatment
      response.
AB  - OBJECTIVES: This investigation explored the onset, progression, socioemotional
      effects, and treatment outcomes of spasmodic dysphonia (SD). METHODS: A cross
      sectional epidemiological approach was used to examine questionnaire responses
      from 150 individuals with SD. RESULTS: Symptoms of SD (mean age at onset, 46
      years) began gradually in 76% of cases and were progressive (ie, failed to
      plateau) in 34% of cases. Botulinum toxin A (Botox) helped to attenuate voice
      symptoms in 91% of cases; however, the scores on the Voice-Related Quality of
      Life questionnaire (V-RQOL) were not associated with this effect. The V-RQOL
      scores improved with time since symptom onset, independent of age and treatment.
      The patients with only SD experienced onset, course, and progression of symptoms
      similar to those of the patients with SD and coexisting vocal tremor.
      CONCLUSIONS: The symptoms of SD begin gradually and worsen over time. New
      evidence indicates that SD symptoms may continue to progress without plateau in
      at least a subset of patients. Individuals with SD and coexisting vocal tremor
      experience symptom trajectories similar to those of patients with SD only.
      Although Botox may attenuate voice symptoms, these effects do not appear to be
      strongly related to the V-RQOL scores. These results provide new and valuable
      insights regarding the onset, course, progression, and treatment of SD.

PMID- 21859057
TI  - Obstructing encephaloceles presenting as chronic rhinosinusitis: lessons learned
      from a case series.
AB  - We present a unique anatomic cause of encephalocele, and describe appropriate
      diagnosis. Two patients underwent stereotactic image-guided sinus surgery for
      presumed chronic rhinosinusitis with intraoperative findings of a sinus
      encephalocele. The first patient underwent a conservative 2-stage management that
      included an initial cerebrospinal fluid (CSF) leak repair followed by
      encephalocele resection. The second patient underwent a 1-stage encephalocele
      resection and CSF leak repair with a septal graft. The sinus surgeon needs to
      consider the possibility of encephalocele when the ethmoid, sphenoid, or, rarely,
      frontal sinuses present with an isolated opacification that does not improve with
      conservative medical therapy.

PMID- 21859058
TI  - Epiglottic repositioning procedure for supraglottic stenosis/collapse.
AB  - OBJECTIVES: Supraglottic stenosis/collapse is an uncommon condition. It can be
      difficult to detect and may be a cause of failed decannulation following
      tracheostomy. We present a novel technique to correct supraglottic
      stenosis/collapse. METHODS: We performed a retrospective analysis of the records
      of patients in whom attempts at decannulation had failed at our center between
      2003 and 2007. A subgroup with supraglottic stenosis/collapse with posterior
      displacement of the base of the epiglottis was identified. Our epiglottic
      repositioning procedure was performed in these patients. Through an external
      incision, the epiglottis was divided above the anterior commissure and attached
      to the superior border of the thyroid cartilage. RESULTS: Eight decannulation
      failures out of 36 attempted decannulations were identified. Three of these 8
      cases involved supraglottic stenosis/collapse due to posterior displacement of
      the base of the epiglottis. Correction of the supraglottic stenosis/collapse led
      to successful decannulation in all cases. CONCLUSIONS: Diagnosis-directed
      laryngoscopy is required to identify this condition. We describe precisely a
      technique of repositioning the epiglottis to correct supraglottic
      stenosis/collapse.

PMID- 21859059
TI  - Removal of tracheobronchial foreign bodies via suspension laryngoscope and
      Hopkins telescope in infants.
AB  - OBJECTIVES: Tracheobronchial foreign body aspiration is a life-threatening
      accident in infants, and is still a formidable clinical emergency to both
      otorhinolaryngologists and anesthesiologists. In this study, we attempted to
      assess the safety and ease of tracheobronchial foreign body removal in infants
      via suspension laryngoscopy and Hopkins telescopy under general anesthesia with
      endotracheal intubation. METHODS: The retrospective clinical study from 2006 to
      2010 included 50 infants with foreign body aspiration, of whom 35 underwent
      suspension laryngoscopy and Hopkins telescopy and the other 15 underwent rigid
      bronchoscopy. All of the procedures were under general anesthesia with
      endotracheal intubation. RESULTS: All of the patients underwent temporary
      extubation. The foreign body was successfully removed in 46 cases and was not
      found in the other 4 cases. The mean operation time in the rigid bronchoscopy
      group was 13.20+/-9.01 minutes, and that in the Hopkins telescopy group was
      5.79+/-3.54 minutes. The oxygen saturation level was below 90% in 17 cases, of
      which 7 were in the rigid bronchoscopy group and 10 were in the Hopkins telescopy
      group. The vital signs, including the partial pressure of carbon dioxide in
      expiratory gas and the heart rate, were stable in all cases. CONCLUSIONS: Foreign
      body removal in infants via suspension laryngoscopy and Hopkins telescopy under
      general anesthesia with endotracheal intubation should be promoted, since it is
      relatively safe and easy for both anesthesiologists and otorhinolaryngologists to
      perform and has a remarkable success rate.

PMID- 21859060
TI  - Effects of levobupivacaine versus bupivacaine infiltration on postoperative
      analgesia in pediatric tonsillectomy patients: a randomized, double-blind,
      placebo-controlled study.
AB  - OBJECTIVES: We compared the effects of levobupivacaine hydrochloride, bupivacaine
      hydrochloride, and saline injections in alleviating posttonsillectomy pain.
      METHODS: Between November 2009 and April 2010, we recruited 60 patients (36 male
      and 24 female) between 2 and 12 years of age into the study. After informed
      consent was obtained from the parents, patients admitted for tonsillectomy were
      randomized into 3 groups by means of sealed envelopes. Group 1 (20 patients; mean
      age, 6.45+/-2.78 years) received 0.9% sodium chloride (saline solution), group 2
      (20 patients; mean age, 5.60+/-2.70 years) received 0.25% levobupivacaine
      hydrochloride, and group 3 (20 patients; mean age, 5.85+/-2.43 years) received
      0.5% bupivacaine hydrochloride infiltrated around each tonsil. Pain was evaluated
      with McGrath's face scale. RESULTS: The postoperative pain scores at 1 and 5
      hours were similar among the groups (p>0.05). The pain scores in the
      levobupivacaine group were lower than those in the saline group at 13 hours
      (p<0.017). The pain scores in the bupivacaine and levobupivacaine groups were
      significantly lower than those in the saline group from 17 to 21 hours until day
      6 (p>0.017). There was no difference between the levobupivacaine and bupivacaine
      groups (p>0.017). CONCLUSIONS: Local infiltration of levobupivacaine is a
      relatively safe and effective method and is equivalent to use of bupivacaine for
      posttonsillectomy pain.

PMID- 21859061
TI  - Covering the kids: the Patient Protection and Affordable Care Act's adult child
      coverage mandate.

PMID- 21859062
TI  - IFHE president gives personal perspective.
AB  - During a recent whistle-stop trip to England, International Federation of
      Hospital Engineering (IFHE) President, Professor Yasushi Nagasawa, and a
      delegation of Japanese student architects and engineers, managed not only to tour
      of a number of London's leading healthcare facilities, and a renewable energy
      facility at London's South Bank University--where the Professor had earlier
      trained, but also visited IHEEM's Portsmouth offices, and viewed medical
      facilities at the city's acute hospital. The Professor also gave a fascinating
      insight into the Japanese healthcare system and Japanese hospital design at an
      evening meeting of IHEEM's London branch.

PMID- 21859063
TI  - Peacetime car park to wartime hospital.
AB  - At last November's 21st IFHE Congress in Tokyo, Israeli architect Arad Sharon
      described how he and his partner at Tel Aviv-based Sharon Architects, Sharon Gur
      Ze'ev, had designed a new children's hospital on Haifa's Rambam Health Care
      campus, one of Israel's best-known healthcare sites, and already home both to the
      region's largest medical centre, and a Level 1 Trauma Centre that treats both
      civilian and military patients. The architects have also designed a 2,000-bed
      subterranean emergency hospital, which will occupy three storeys below, that will
      serve as patient, visitor, and staff car parking during peacetime, but be rapidly
      convertible for medical use in times of conflict.

PMID- 21859064
TI  - Numerous ways to answer the call.
AB  - Like other communications technology, nurse call systems have evolved
      considerably over the past 10-15 years, and now offer far more than just their
      primary function. HEJ editor Jonathan Baillie discussed, with several leading UK
      based suppliers, some of the available technologies, considered their pros and
      cons, and asked senior personnel how they see nurse call systems developing in
      the short to medium term as demand for an ever wider range of features, and
      convergence with other equipment, continue to grow.

PMID- 21859065
TI  - Faster Legionella testing on horizon.
AB  - While the "traditional" way to measure Legionella quantitatively in water is
      based on a complex culture method where results can take up to 14 days, the last
      few years have seen the availability of very rapid real-time monitoring of the
      bacterium in water systems, with the development of quantitative polymerase chain
      reaction (qPCR), a process which gives results "within hours". To date, however,
      a lack of consensus on how to interpret such results in relation to those from
      culture has been a stumbling block, although, as Susan Pearson, a freelance
      journalist and public relations consultant specialising in medicine and the
      environment, reports, the positive results of a recent multi-centre European
      study mean this could soon all change.

PMID- 21859066
TI  - BEMS systems give developer sixth sense.
AB  - Duty-bound under contracts with partner NHS PCTs, independent primary care
      contractors, and other community stakeholders who lease healthcare premises from
      it, to ensure that the buildings' energy systems and plant run efficiently and
      cost-effectively, Community Solutions, a leading investor in, and developer of,
      UK community-based health, social, and local authority services, is now
      standardising on Trend Controls' building energy management systems to ensure
      that such vital equipment runs within defined parameters, and that facilities
      without FM personnel on site day-to-day are kept both comfortable to work in, and
      fit-for-purpose.

PMID- 21859067
TI  - Responsive service at West Kent sites.
AB  - Operations manager, Ashley Heming, and area sales manager, Andy Cassie, of
      specialist cleaning and cleaning services company, CK Group, explain how a close
      15-year relationship with Kent's Maidstone and Tunbridge Wells NHS Trust is
      continuing, with the firm having recently undertaken a thorough preoccupation
      clean at the new 513-bed PFI-funded Pembury Hospital, one of the UK's first acute
      hospitals to offer 100% single-bed en suite accommodation, before its first
      patients moved in. As HEJ editor Jonathan Baillie explains, the company will
      undertake similar work for further phases, and has also provided a specialist
      decontamination service on Victorian buildings set for demolition at the site.

PMID- 21859068
TI  - 'A virtuous circle' of climate control.
AB  - As one of the UK's largest public sector carbon emitters, the NHS is under
      particularly strong pressure to deliver action to reduce its CO2 emissions and
      meet Government targets, while joining other public sector organisations in
      leading the vanguard against climate change. Simon Keel, product executive at air
      conditioning specialist, Daikin UK, points out that this pressure has manifested
      itself in "a constant stream of legislation, standards, and regulations",
      resulting in many health estate managers feeling "bogged down and even a little
      confused". Here he examines some of the key requirements and "contradictions" of
      carbon reduction legislation for air conditioning, and how managers can best
      address them.

PMID- 21859069
TI  - Experience invaluable at 'live site' upgrade.
AB  - Global provider of professional technical and management support services to the
      transportation, facilities, environmental, energy, water, and government sectors,
      AECOM, describes how it is providing a package of advanced civil and structural
      engineering design solutions to the Leeds Teaching Hospitals NHS Trust as the
      Trust undertakes a major infrastructure upgrade at its St James's University
      Hospital and Leeds General Infirmary (LGI) sites.

PMID- 21859070
TI  - Homopolar dihydrogen bonding in alkali-metal amidoboranes and its implications
      for hydrogen storage.
AB  - The solid-state structures of LiNH(2)BH(3) and NaNH(2)BH(3) have been shown
      recently to exhibit intricate M(delta+)...(delta-)H-B and N-H(delta+)...(delta-)H
      B interactions. However, closer inspection of these structures reveals additional
      homopolar H...H interactions, viz., B-H(delta-)...(delta-)H-B and N
      H(delta+)...(delta+)H-N, which contribute to the relative stability of the
      extended structures of these crystalline materials. In addition, an NMR study of
      the isotopomer LiND(2)BH(3) shows that a significant quantity of H(2) is desorbed
      thermally along with HD, which can only arise from hydride-hydride interactions,
      either directly from B-H(delta-)...(delta-)H-B moieties or indirectly through the
      participation of Li-H intermediates.

PMID- 21859071
TI  - The curious case of the hydrated proton.
AB  - Understanding the hydrated proton is a critically important problem that
      continues to engage the research efforts of chemists, physicists, and biologists
      because of its involvement in a wide array of phenomena. Only recently have
      several unique properties of the hydrated proton been unraveled through computer
      simulations. One such process is the detailed molecular mechanism by which
      protons hop between neighboring water molecules, thus giving rise to the
      anomalously high diffusion of protons relative to other simple cations. Termed
      Grotthuss shuttling, this process occurs over multiple time and length scales,
      presenting unique challenges for computer modeling and simulation. Because the
      hydrated proton is in reality a dynamical electronic charge defect that spans
      multiple water molecules, the simulation methodology must be able to dynamically
      readjust the chemical bonding topology. This reactive nature of the chemical
      process is automatically captured with ab initio molecular dynamics (AIMD)
      simulation methods, where the electronic degrees of freedom are treated
      explicitly. Unfortunately, these calculations can be prohibitively expensive for
      more complex proton solvation and transport phenomena in the condensed phase.
      These AIMD simulations remain extremely valuable, however, in validating
      empirical models, verifying results, and providing insight into molecular
      mechanisms.  In this Account, we discuss recent progress in understanding the
      solvation and transport properties of the hydrated excess proton. The advances
      are based on results obtained from reactive molecular dynamics simulations using
      the multistate empirical valence bond (MS-EVB) methodology. This approach relies
      on a dynamic linear combination of chemical bond topologies to model charge
      delocalization and dynamic bonding environments. When parametrized via a
      variational force-matching algorithm from AIMD trajectories, the MS-EVB method
      can be viewed as a multiscale bridging of ab initio simulation results to a
      simpler and more efficient representation. The process allows sampling of longer
      time and length scales, which would normally be too computationally expensive
      with AIMD alone.  With the MS-EVB methodology, the statistically important
      components of the excess proton solvation and hopping mechanisms in liquid water
      have been identified. The most likely solvation structure for the hydrated proton
      is a distorted Eigen-type complex (H(9)O(4)(+)). In this state, the excess proton
      charge defect rapidly resonates between three possible distorted Eigen-type
      structures until a successful proton hop occurs. This process, termed the
      "special-pair dance", serves as a kind of preparatory phase for the proton
      hopping while the neighboring water hydrogen-bonding network fluctuates and
      ultimately rearranges to facilitate a proton hop.  The modifications of the
      solvation structure and transport properties of the excess proton in concentrated
      acid solutions were further investigated. The Eigen-type solvation structure also
      possesses both "hydrophilic" and "hydrophobic" sides, which accounts for the
      affinity of the hydrated proton for the air-water interface. This unusual
      "amphiphilic" character of the hydrated proton further leads to the metastable
      formation of contact ion pairs between two hydrated protons. It also engenders a
      surprisingly constant degree of solubility of hydrophobic species as a function
      of acid concentration, which contrasts with a markedly variable solubility as a
      function of salt (such as NaCl or KCl) concentration.

PMID- 21859072
TI  - Spectroscopic and computational studies of glutathionylcobalamin: nature of Co-S
      bonding and comparison to Co-C bonding in coenzyme B12.
AB  - Glutathionylcobalamin (GSCbl) is a unique, biologically relevant cobalamin
      featuring an axial Co-S bond that distinguishes it from the enzymatically active
      forms of vitamin B(12), which possess axial Co-C bonds. GSCbl has been proposed
      to serve as an intermediate in cobalamin processing and, more recently, as a
      therapeutic for neurological disorders associated with oxidative stress. In this
      study, GSCbl and its close relative cysteinylcobalamin (CysCbl) were investigated
      using electronic absorption, circular dichroism, magnetic circular dichroism, and
      resonance Raman spectroscopies. The spectroscopic data were analyzed in the
      framework of density functional theory (DFT) and time-dependent DFT computations
      to generate experimentally validated electronic structure descriptions. Although
      the change in the upper axial ligand from an alkyl to a thiol group represents a
      major perturbation in terms of the size, basicity, and polarizability of the
      coordinating atom, our spectroscopic and computational results reveal striking
      similarities in electronic structure between methylcobalamin (MeCbl) and GSCbl,
      especially with regard to the sigma donation from the alkyl/thiol ligand and the
      extent of mixing between the cobalt 3d and the ligand frontier orbitals. A
      detailed comparison of Co-C and Co-S bonding in MeCbl and GSCbl, respectively, is
      presented, and the implications of our results with respect to the proposed
      biological roles of GSCbl are discussed.

PMID- 21859073
TI  - Disproportionation of O-methylhydroxylamine catalyzed by
      aquapentacyanoferrate(II).
AB  - The aquapentacyanoferrate(II) ion, [Fe(II)(CN)(5)H(2)O](3-), catalyzes the
      disproportionation reaction of O-methylhydroxylamine, NH(2)OCH(3), with
      stoichiometry 3NH(2)OCH(3) -> NH(3) + N(2) + 3CH(3)OH. Kinetic and spectroscopic
      evidence support an initial N coordination of NH(2)OCH(3) to
      [Fe(II)(CN)(5)H(2)O](3-) followed by a homolytic scission leading to radicals
      [Fe(II)(CN)(5)(*)NH(2)](3-) (a precursor of Fe(III) centers and bound NH(3)) and
      free methoxyl, CH(3)O(*), thus establishing a radical path leading to N
      methoxyamino ((*)NHOCH(3)) and 1,2-dimethoxyhydrazine, (NHOCH(3))(2). The latter
      species is moderately stable and proposed to be the precursor of N(2) and most of
      the generated CH(3)OH. Intermediate [Fe(III)(CN)(5)L](2-) complexes (L = NH(3),
      H(2)O) form dinuclear cyano-bridged mixed-valent species, affording a catalytic
      substitution of the L ligands promoted by [Fe(II)(CN)(5)L](3-). Free or bound
      NH(2)OCH(3) may act as reductants of [Fe(III)(CN)(5)L](2-), thus regenerating
      active sites. At increasing concentrations of NH(2)OCH(3) a coordinated diazene
      species emerges, [Fe(II)(CN)(5)N(2)H(2)](3-), which is consumed by the oxidizing
      CH(3)O(*), giving N(2) and CH(3)OH. Another side reaction forms
      [Fe(II)(CN)(5)N(O)CH(3)](3-), an intermediate containing the nitrosomethane
      ligand, which is further oxidized to the nitroprusside ion, [Fe(II)(CN)(5)NO](2
      ). The latter is a final oxidation product with a significant conversion of the
      initial [Fe(II)(CN)(5)H(2)O](3-) complex. The side reaction partially blocks the
      Fe(II)-aqua active site, though complete inhibition is not achieved because the
      radical path evolves faster than the formation rates of the Fe(II)-NO(+) bonds.

PMID- 21859074
TI  - Gadolinium DOTA chelates featuring alkyne groups directly grafted on the tetraaza
      macrocyclic ring: synthesis, relaxation properties, "click" reaction, and high
      relaxivity micelles.
AB  - This paper reports on the synthesis and relaxivity properties of tetraacetic DOTA
      type chelating agents featuring one or two alkyne groups directly grafted on the
      tetraaza macrocyclic ring and available for "click" reactions with azide-bearing
      substrates. The racemic DOTAma ligand bearing one alkyne group was obtained by a
      bisaminal template route. The same approach was used to prepare ligand DOTAda
      substituted by two alkyne groups located on two adjacent carbon atoms. The S,S
      enantiomer of DOTAda was also prepared by a "crab-like" condensation. This ligand
      is the first example of a DOTA derivative featuring two reactive functions
      adjacent to each other on the macrocyclic ring. A triacetic monoalkyne ligand
      (DO3ma) was also synthesized for comparison purposes. NMR studies indicate that
      the Yb(III) chelates of DOTAma and DOTAda adopt two conformations in solutions in
      which the tetraaza ring is rigidified. The hydration state of the Eu(III)
      chelates was determined by luminescence spectroscopy, and the water exchange time
      of the Gd(III) complexes was measured by (17)O NMR. Ring substitution accelerates
      the water exchange. These data were used to interpret nuclear magnetic relaxation
      dispersion curves of the Gd(III) chelates. Two long aliphatic chains have been
      added to DOTAda by a "click" procedure to form the (C18)(2)DOTAda ligand. The
      corresponding Gd(III) complex forms micelles of unusually high relaxivity
      presumably because of the close proximity of the aliphatic chains on the
      macrocyclic ring that ensures a rigid double anchoring into the micelles.

PMID- 21859075
TI  - Carboxylate-free Mn(III)2Ln(III)2 (Ln = lanthanide) and Mn(III)2Y(III)2 complexes
      from the use of (2-hydroxymethyl)pyridine: analysis of spin frustration effects.
AB  - The initial employment of 2-(hydroxymethyl)pyridine for the synthesis of Mn/Ln
      (Ln = lanthanide) and Mn/Y clusters, in the absence of an ancillary organic
      ligand, has afforded a family of tetranuclear
      [Mn(III)(2)M(III)(2)(OH)(2)(NO(3))(4)(hmp)(4)(H(2)O)(4)](NO(3))(2) (M = Dy, 1;
      Tb, 2; Gd, 3; Y; 4) anionic compounds. 1-4 possess a planar butterfly (or
      rhombus) core and are rare examples of carboxylate-free Mn/Ln and Mn/Y clusters.
      Variable-temperature dc and ac studies established that 1 and 2, which contain
      highly anisotropic Ln(III) atoms, exhibit slow relaxation of their magnetization
      vector. Fitting of the obtained magnetization (M) versus field (H) and
      temperature (T) data for 3 by matrix diagonalization and including only axial
      anisotropy (zero-field splitting, ZFS) showed the ground state to be S = 3.
      Complex 4 has an S = 0 ground state. Fitting of the magnetic susceptibility data
      collected in the 5-300 K range for 3 and 4 to the appropriate van Vleck equations
      revealed, as expected, extremely weak antiferromagnetic interactions between the
      paramagnetic ions; for 3, J(1) = -0.16(2) cm(-1) and J(2) = -0.12(1) cm(-1) for
      the Mn(III)...Mn(III) and Mn(III)...Gd(III) interactions, respectively. The S = 3
      ground state of 3 has been rationalized on the basis of the spin frustration
      pattern in the molecule. For 4, J = -0.75(3) cm(-1) for the Mn(III)...Mn(III)
      interaction. Spin frustration effects in 3 have been quantitatively analyzed for
      all possible combinations of sign of J(1) and J(2).

PMID- 21859076
TI  - General approach for monitoring peptide-protein interactions based on graphene
      peptide complex.
AB  - Peptide-protein interactions have critical roles in biology. Monitoring peptide
      protein interactions plays an important role in investigating molecular
      recognition, screening drugs, and designing biosensors. In this paper, we develop
      a novel fluorescent approach to monitor peptide-protein interactions based on the
      assembly of pyrene-labeled peptide and graphene oxide (GO). The pyrene-labeled
      peptide is strongly adsorbed on the surface of GO via pi-pi interactions and
      hydrophobic interactions. As a result, the proximity of the GO to the pyrene
      moiety effectively quenches the fluorescence of pyrene. In the presence of target
      protein, the competitive binding of the target protein with GO for peptide
      results in the restoration of fluorescence signal. This signaling mechanism makes
      it possible to monitor the peptide-protein interactions in a homogeneous real
      time format.

PMID- 21859077
TI  - Large-scale identification of calcium oxalate monohydrate crystal-binding
      proteins on apical membrane of distal renal tubular epithelial cells.
AB  - Adhesion of calcium oxalate monohydrate (COM) crystals onto apical surface of
      renal tubular epithelial cells is a crucial mechanism for crystal retention,
      leading to kidney stone formation. Various proteins on apical membrane may bind
      to COM crystals; however, these crystal-binding proteins remained unidentified.
      The present study therefore aimed to identify COM crystal-binding proteins on
      apical membrane of distal renal tubular epithelial cells. Madin-Darby Canine
      Kidney (MDCK) cells were cultivated to be polarized epithelial cells and apical
      membrane was isolated from these cells using a peeling method established
      recently. Enrichment and purity of isolated apical membrane were confirmed by
      Western blot analysis for specific markers of apical (gp135) and basolateral
      (Na(+)/K(+)-ATPase) membranes. Proteins derived from the isolated apical membrane
      were then resuspended in artificial urine and incubated with COM crystals. The
      bound proteins were eluted, resolved by SDS-PAGE, and analyzed by Q-TOF MS and
      MS/MS, which identified 96 proteins. Among these, expression and localization of
      annexin II on apical surface of MDCK cells were confirmed by Western blot
      analysis, immunofluorescence staining, and laser-scanning confocal microscopic
      examination. Finally, the function of annexin II as the COM crystal-binding
      protein was successfully validated by COM crystal-binding assay. This large data
      set offers many opportunities for further investigations of kidney stone disease
      and may lead to the development of new therapeutic targets.

PMID- 21859078
TI  - Combination of two pharmacophoric systems: synthesis and pharmacological
      evaluation of spirocyclic pyranopyrazoles with high sigma1 receptor affinity.
AB  - The novel class of spirocyclic sigma(1) ligands 3 (6',7'-dihydro-1'H
      spiro[piperidine-4,4'-pyrano[4,3-c]pyrazoles]) was designed by the combination of
      the potent sigma(1) ligands 1 and 2 in one molecule. Thorough structure affinity
      relationships were derived by the variation of the substituents in position 1',
      1, and 6'. Whereas the small electron rich methylpyrazole heterocycle was less
      tolerated by the sigma(1) receptor protein, the introduction of a phenyl
      substituent instead of the methyl group led to ligands with a high sigma(1)
      affinity. It is postulated that the additional phenyl substituent occupies a
      previously unrecognized hydrophobic region of the sigma(1) receptor resulting in
      additional lipophilic interactions. The spirocyclic pyranopyrazoles are very
      selective against the sigma(2) subtype, the PCP binding site of the NMDA
      receptor, and further targets. Despite high sigma(1) affinity, the
      cyclohexylmethyl derivative 17i (K(i) (sigma(1)) = 0.55 nM) and the isopentenyl
      derivative 17p (K(i) (sigma(1)) = 1.6 nM) showed only low antiallodynic activity
      in the capsaicin assay.

PMID- 21859079
TI  - Diameter scaling of the optical band gap in individual CdSe nanowires.
AB  - The diameter dependence of the optical band gap of single CdSe nanowires (NWs) is
      investigated by a combination of atomic force microscopy, scanning fluorescence
      microscopy, and transmission electron microscopy. We find a good congruence of
      the experimental data to calculations within the effective mass approximation
      taking into account quantization, exciton Coulomb interaction, and dielectric
      mismatch. The experimental data are furthermore compared to different theoretical
      approaches. We discuss the influence of alternating wurtzite and zinc blende
      segments along the NWs on their optical properties.

PMID- 21859081
TI  - High quantum efficiency of band-edge emission from ZnO nanowires.
AB  - External quantum efficiency (EQE) of photoluminescence as high as 20% from
      isolated ZnO nanowires were measured at room temperature. The EQE was found to be
      highly dependent on photoexcitation density, which underscores the importance of
      uniform optical excitation during the EQE measurement. An integrating sphere
      coupled to a microscopic imaging system was used in this work, which enabled the
      EQE measurement on isolated ZnO nanowires. The EQE values obtained here are
      significantly higher than those reported for ZnO materials in forms of bulk, thin
      films or powders. Additional insight on the radiative extraction factor of one
      dimensional nanostructures was gained by measuring the internal quantum
      efficiency of individual nanowires. Such quantitative EQE measurements provide a
      sensitive, noninvasive method to characterize the optical properties of low
      dimensional nanostructures and allow tuning of synthesis parameters for
      optimization of nanoscale materials.

PMID- 21859080
TI  - Reduction of the [2Fe-2S] cluster accompanies formation of the intermediate 9
      mercaptodethiobiotin in Escherichia coli biotin synthase.
AB  - Biotin synthase catalyzes the conversion of dethiobiotin (DTB) to biotin through
      the oxidative addition of sulfur between two saturated carbon atoms, generating a
      thiophane ring fused to the existing ureido ring. Biotin synthase is a member of
      the radical SAM superfamily, composed of enzymes that reductively cleave S
      adenosyl-l-methionine (SAM or AdoMet) to generate a 5'-deoxyadenosyl radical that
      can abstract unactivated hydrogen atoms from a variety of organic substrates. In
      biotin synthase, abstraction of a hydrogen atom from the C9 methyl group of DTB
      would result in formation of a dethiobiotinyl methylene carbon radical, which is
      then quenched by a sulfur atom to form a new carbon-sulfur bond in the
      intermediate 9-mercaptodethiobiotin (MDTB). We have proposed that this sulfur
      atom is the MU-sulfide of a [2Fe-2S](2+) cluster found near DTB in the enzyme
      active site. In the present work, we show that formation of MDTB is accompanied
      by stoichiometric generation of a paramagnetic FeS cluster. The electron
      paramagnetic resonance (EPR) spectrum is modeled as a 2:1 mixture of components
      attributable to different forms of a [2Fe-2S](+) cluster, possibly distinguished
      by slightly different coordination environments. Mutation of Arg260, one of the
      ligands to the [2Fe-2S] cluster, causes a distinctive change in the EPR spectrum.
      Furthermore, magnetic coupling of the unpaired electron with (14)N from Arg260,
      detectable by electron spin envelope modulation (ESEEM) spectroscopy, is observed
      in WT enzyme but not in the Arg260Met mutant enzyme. Both results indicate that
      the paramagnetic FeS cluster formed during catalytic turnover is a [2Fe-2S](+)
      cluster, consistent with a mechanism in which the [2Fe-2S](2+) cluster
      simultaneously provides and oxidizes sulfide during carbon-sulfur bond formation.

PMID- 21859082
TI  - Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from
      Leucophyllum frutescens.
AB  - Bioactivity-guided fractionation of the methanolic root bark extract of
      Leucophyllum frutescens led to the identification of leubethanol (1), a new
      serrulatane-type diterpene with activity against both multi-drug-resistant and
      drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1)
      was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane
      (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the
      range 6.25-12.50 MUg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D
      NOE experiments, from 1H NMR full spin analysis, and by comparison of the
      experimental vibrational circular dichroism (VCD) spectrum to density functional
      theory calculated VCD spectra of two diastereomers.

PMID- 21859083
TI  - Palladium(II)-catalyzed direct alkoxylation of arenes: evidence for solvent
      assisted concerted metalation deprotonation.
AB  - Density functional theory investigations on the mechanism of palladium acetate
      catalyzed direct alkoxylation of N-methoxybenzamide in methanol reveal that the
      key steps involve solvent-assisted N-H as well as C-H bond activations. The
      transition state for the critical palladium-carbon bond formation through a
      concerted metalation deprotonation (CMD) process leading to a palladacycle
      intermediate has been found to be more stable in the methanol-assisted pathway as
      compared to an unassisted route.

PMID- 21859084
TI  - Insertion of arynes into thioureas: a new amidine synthesis.
AB  - Arynes, generated from trimethylsilyl phenyltriflate precursors, have been found
      to react with thioureas via a formal pi-insertion into the C?S bond. The reaction
      contrasts with that of ureas, which proceeds via benzyne sigma-insertion into the
      C-N bond, and represents a new, operationally simple route to functionalized
      amidines.

PMID- 21859085
TI  - Microfabricated gas chromatograph for the selective determination of
      trichloroethylene vapor at sub-parts-per-billion concentrations in complex
      mixtures.
AB  - A complete field-deployable microfabricated gas chromatograph (MUGC) is
      described, and its adaptation to the analysis of low- and subparts-per-billion
      (ppb) concentrations of trichloroethylene (TCE) vapors in complex mixtures is
      demonstrated through laboratory testing. The specific application being addressed
      concerns the problem of indoor air contamination by TCE vapor intrusion. The MUGC
      prototype employs a microfabricated focuser, dual microfabricated separation
      columns, and a microsensor array. These are interfaced to a nonmicrofabricated
      front-end pretrap and high-volume sampler module to reduce analysis time and
      limits of detection (LOD). Selective preconcentration and focusing are coupled
      with rapid chromatographic separation and multisensor detection for the
      determination of TCE in the presence of up to 45 interferences. Autonomous
      operation is possible via a laptop computer. Preconcentration factors as high as
      500 000 are achieved. Sensitivities are constant over the range of captured TCE
      masses tested (i.e., 9-390 ng), and TCE is measured in a test atmosphere at 120
      parts-per-trillion (ppt), with a projected LOD of 40 ppt (4.2 ng captured, 20 L
      sample) and a maximum sampling + analytical cycle time of 36 min. Short- and
      medium-term (1 month) variations in retention time, absolute responses, and
      response patterns are within acceptable limits.

PMID- 21859086
TI  - Catalytic asymmetric thiofunctionalization of unactivated alkenes.
AB  - Catalytic asymmetric sulfenylation of double bonds has been achieved using a
      BINAM-based phosphoramide catalyst and an electrophilic sulfur source. Simple
      alkenes as well as styrenes afforded sulfenylated tetrahydrofurans and
      tetrahydropyrans by closure with pendant hydroxyl or carboxyl groups.
      Intermolecular thiofunctionalizations were also achieved with simple alcohols or
      carboxylic acids as the nucleophiles.

PMID- 21859087
TI  - Synthesis, characterization, and catalase activity of a water-soluble diMn(III)
      complex of a sulphonato-substituted Schiff base ligand: an efficient catalyst for
      H2O2 disproportionation.
AB  - A new diMn(III) complex, Na[Mn(2)(3-Me-5-SO(3)-salpentO)(MU-MeO)(MU
      AcO)(H(2)O)].4H(2)O (1), where salpentOH = 1,5-bis(salicylidenamino) pentan-3-ol,
      was synthesized and structurally characterized. The complex possesses a bis(MU
      alkoxo)(MU-acetato) triply bridged diMn(III) core, the structure of which is
      retained upon dissolution. Complex 1 is highly efficient to disproportionate
      H(2)O(2) in an aqueous solution of pH >= 8.5 or in DMF, with only a slight
      decrease of activity. Electrospray ionization mass spectrometry, EPR, and UV-vis
      spectroscopy used to monitor the H(2)O(2) disproportionation in buffered basic
      medium, suggest that the major active form of the catalyst during cycling occurs
      in the Mn(III)(2) oxidation state and that the starting complex retains the
      dinuclearity and composition during catalysis, with the acetate that moves from
      bridging to terminal ligand. UV-vis and Raman spectroscopy of H(2)O(2) + 1 +
      Bu(4)NOH mixtures in DMF suggest that the catalytic cycle involves
      Mn(III)(2)/Mn(IV)(2) oxidation levels. At pH 10.6 in an Et(3)N/Et(3)NH(+) buffer,
      complex 1 catalyzes dismutation of H(2)O(2) with saturation kinetics on the
      substrate, first order dependence on the catalyst, and k(cat)/K(M) = 16(1) *
      10(2) s(-1) M(-1). During catalysis, the exogenous base contributes to retain the
      integrity of the bis(MU-alkoxo) doubly bridged diMn core and favors the formation
      of the catalyst-peroxide adduct (low value of K(M)), rendering 1 a highly
      efficient catalyst for H(2)O(2) disproportionation.

PMID- 21859088
TI  - Organic dye bearing asymmetric double donor-pi-acceptor chains for dye-sensitized
      solar cells.
AB  - A novel efficient metal free sensitizer containing asymmetric double donor-pi
      acceptor chains (DC) was synthesized for dye-sensitized solar cells (DSSCs).
      Comparing to 3.80%, 4.40% and 4.64% for the DSSCs based on the dyes with single
      chain (SC1, SC2) and cosensitizers (SC1 + SC2), the overall conversion efficiency
      reaches 6.06% for DC-sensitized solar cells as a result of its longer electron
      lifetime and higher incident monochromatic photon-to-current conversion
      efficiency.

PMID- 21859089
TI  - Nuclear inclusion of nontargeted and chromatin-targeted polystyrene beads and
      plasmid DNA containing nanoparticles.
AB  - The nuclear membrane is one of the major cellular barriers in the delivery of
      plasmid DNA (pDNA). Cell division has a positive influence on the expression
      efficiency since, at the end of mitosis, pDNA or pDNA containing complexes near
      the chromatin are probably included by a random process in the nuclei of the
      daughter cells. However, very little is known about the nuclear inclusion of
      nanoparticles during cell division. Using the Xenopus nuclear envelope reassembly
      (XNER) assay, we found that the nuclear enclosure of nanoparticles was dependent
      on size (with 100 and 200 nm particles being better included than the 500 nm
      ones) and charge (with positively charged particles being better included than
      negatively charged or polyethyleneglycolated (PEGylated) ones) of the beads.
      Also, coupling chromatin-targeting peptides to the polystyrene beads or pDNA
      complexes improved their inclusion by 2- to 3-fold. Upon microinjection in living
      HeLa cells, however, nanoparticles were never observed in the nuclei of cells
      postdivision but accumulated in a specific perinuclear region, which was
      identified as the lysosomal compartment. This indicates that nanoparticles can
      end up in the lysosomes even when they were not delivered through endocytosis. To
      elucidate if the chromatin binding peptides also have potential in living cells,
      this additional barrier first has to be tackled, since it prevents free particles
      from being present near the chromatin at the moment of cell division.

PMID- 21859090
TI  - Generation of autonomous activity of Ca(2+)/calmodulin-dependent protein kinase
      kinase beta by autophosphorylation.
AB  - Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) phosphorylate and
      activate specific downstream protein kinases, including CaMKI, CaMKIV, and 5'-AMP
      activated protein kinase, which mediates a variety of Ca(2+) signaling cascades.
      CaMKKs have been shown to undergo autophosphorylation, although their role in
      enzymatic regulation remains unclear. Here, we found that CaMKKalpha and beta
      isoforms expressed in nonstimulated transfected COS-7 cells, as well as
      recombinant CaMKKs expressed in and purified from Escherichia coli, were
      phosphorylated at Thr residues. Introduction of a kinase-dead mutation completely
      impaired the Thr phosphorylation of these recombinant CaMKK isoforms. In
      addition, wild-type recombinant CaMKKs were unable to transphosphorylate the
      kinase-dead mutants, suggesting that CaMKK isoforms undergo Ca(2+)/CaM
      independent autophosphorylation in an intramolecular manner. Liquid
      chromatography-tandem mass spectrometry analysis identified Thr(482) in the
      autoinhibitory domain as one of the autophosphorylation sites in CaMKKbeta, but
      phosphorylation of the equivalent Thr residue (Thr(446)) in the alpha isoform was
      not observed. Unlike CaMKKalpha that has high Ca(2+)/CaM-dependent activity, wild
      type CaMKKbeta displays enhanced autonomous activity (Ca(2+)/CaM-independent
      activity, 71% of total activity). This activity was significantly reduced (to
      37%) by substitution of Thr(482) with a nonphosphorylatable Ala, without
      significant changes in Ca(2+)/CaM binding. In addition, a CaMKKalpha mutant
      containing the CaMKKbeta regulatory domain was shown to be partially
      phosphorylated at Thr(446), resulting in a modest elevation of its autonomous
      activity. The combined results indicate that, in contrast to the alpha isoform,
      CaMKKbeta exhibited increased autonomous activity, which was caused, at least in
      part, by autophosphorylation at Thr(482), resulting in partial disruption of the
      autoinhibitory mechanism.

PMID- 21859091
TI  - Influence of simulated deep frying on the antioxidant fraction of vegetable oils
      after enrichment with extracts from olive oil pomace.
AB  - The stability of the antioxidant fraction in edible vegetable oils has been
      evaluated during a simulated deep frying process at 180  degrees C. Four edible
      oils (i.e., extra-virgin olive oil with a 400 MUg/mL overall content in naturally
      existing phenols; high-oleic sunflower oil without natural content of these
      compounds but enriched either with hydrophilic antioxidants isolated from olive
      pomace or with an oxidation inhibitor, dimethylsiloxane; and sunflower oil
      without enrichment) were subjected to deep heating consisting of 20 cycles at 180
      degrees C for 5 min each. An oil aliquot was sampled after each heating cycle to
      study the influence of heating on the antioxidant fraction composed of
      hydrophilic and lipophilic antioxidants such as phenols and tocopherols,
      respectively. The decomposition curves for each group of compounds caused by the
      influence of deep heating were studied to compare their resistance to oxidation.
      Thus, the suitability of olive pomace as raw material to obtain these compounds
      offers an excellent alternative to the use of olive-tree materials different from
      leaves. The enrichment of refined edible oils with natural antioxidants from
      olive pomace is a sustainable strategy to take benefits from this residue.

PMID- 21859092
TI  - Growth of CuInSe2 and In2Se3/CuInSe2 nano-heterostructures through solid state
      reactions.
AB  - In(2)Se(3) is an essential phase change material and CuInSe(2) is the fundamental
      basis of the copper-indium-gallium-diselenide (CIGS) solar energy material. In
      this paper, we demonstrate the feasibility to transform the phase change material
      to the solar energy material via the solid state reaction. The In(2)Se(3)
      nanobelts (NBs) were synthesized via the vapor-liquid-solid mechanism. The
      chemical composition and the optical properties were investigated by energy
      dispersive spectroscopy, X-ray photoelectron spectroscopy, and reflectance and
      photoluminescence spectra. In the in situ observation of the solid state reaction
      with Cu to form the CuInSe(2) NBs with ultrahigh vacuum transmission electron
      microscopy, we observed the In(2)Se(3)/CuInSe(2) transformation at atomic scale
      in real time. The progression of the atomic layer at the interface provided the
      pertinent information on the kinetic mechanism. In(2)Se(3)/CuInSe(2) nano
      heterostructures were also obtained in the present investigation. The approach to
      the CIGS nanosolar cell was also proposed. This study shall be beneficial in the
      development of high-performance nanowire solar cells and nanodevices with
      In(2)Se(3)/CuInSe(2) nano-heterostructures.

PMID- 21859093
TI  - Dynamically modulating the surface plasmon resonance of doped semiconductor
      nanocrystals.
AB  - Localized surface plasmon absorption features arise at high doping levels in
      semiconductor nanocrystals, appearing in the near-infrared range. Here we show
      that the surface plasmons of tin-doped indium oxide nanocrystal films can be
      dynamically and reversibly tuned by postsynthetic electrochemical modulation of
      the electron concentration. Without ion intercalation and the associated material
      degradation, we induce a > 1200 nm shift in the plasmon wavelength and a factor
      of nearly three change in the carrier density.

PMID- 21859094
TI  - 2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazines: new variant of an old template
      and application to the discovery of anaplastic lymphoma kinase (ALK) inhibitors
      with in vivo antitumor activity.
AB  - A novel 2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazine scaffold has been
      designed as a new kinase inhibitor platform mimicking the bioactive conformation
      of the well-known diaminopyrimidine motif. The design, synthesis, and validation
      of this new pyrrolo[2,1-f][1,2,4]triazine scaffold will be described for
      inhibitors of anaplastic lymphoma kinase (ALK). Importantly, incorporation of
      appropriate potency and selectivity determinants has led to the discovery of
      several advanced leads that were orally efficacious in animal models of
      anaplastic large cell lymphoma (ALCL). A lead inhibitor (30) displaying superior
      efficacy was identified and in depth in vitro/in vivo characterization will be
      presented.

PMID- 21859095
TI  - Reversible nanopore formation in Ge nanowires during lithiation-delithiation
      cycling: an in situ transmission electron microscopy study.
AB  - Retaining the high energy density of rechargeable lithium ion batteries depends
      critically on the cycle stability of microstructures in electrode materials. We
      report the reversible formation of nanoporosity in individual germanium nanowires
      during lithiation-delithiation cycling by in situ transmission electron
      microscopy. Upon lithium insertion, the initial crystalline Ge underwent a two
      step phase transformation process: forming the intermediate amorphous Li(x)Ge and
      final crystalline Li(15)Ge(4) phases. Nanopores developed only during
      delithiation, involving the aggregation of vacancies produced by lithium
      extraction, similar to the formation of porous metals in dealloying. A
      delithiation front was observed to separate a dense nanowire segment of
      crystalline Li(15)Ge(4) with a porous spongelike segment composed of
      interconnected ligaments of amorphous Ge. This front sweeps along the wire with a
      logarithmic time law. Intriguingly, the porous nanowires exhibited fast
      lithiation/delithiation rates and excellent mechanical robustness, attributed to
      the high rate of lithium diffusion and the porous network structure for facile
      stress relaxation, respectively. These results suggest that Ge, which can develop
      a reversible nanoporous network structure, is a promising anode material for
      lithium ion batteries with superior energy capacity, rate performance, and cycle
      stability.

PMID- 21859096
TI  - Morphology and temperature dependence of the thermal conductivity of nanoporous
      SiGe.
AB  - Using molecular dynamics simulations, we show that the thermal conductivity
      (kappa) of Si(0.5)Ge(0.5) can be reduced by more than one order of magnitude by
      etching nanometer-sized holes in the material, and it becomes almost constant as
      a function of temperature between 300 and 1100 K for samples with 1 nm wide
      pores. In nanoporous SiGe, thermal conduction is largely determined by mass
      disorder and boundary scattering, and thus the dependence of kappa on pore
      distance and on structural, atomistic disorder is much weaker than in the case of
      nanoporous Si. This indicates that one may minimize kappa of the alloy with less
      stringent morphological constraints than for pure Si.

PMID- 21859097
TI  - Inorganic-organic hybrid solar cell: bridging quantum dots to conjugated polymer
      nanowires.
AB  - Quantum dots show great promise for fabrication of hybrid bulk heterojunction
      solar cells with enhanced power conversion efficiency, yet controlling the
      morphology and interface structure on the nanometer length scale is challenging.
      Here, we demonstrate quantum dot-based hybrid solar cells with improved
      electronic interaction between donor and acceptor components, resulting in
      significant improvement in short-circuit current and open-circuit voltage. CdS
      quantum dots were bound onto crystalline P3HT nanowires through solvent-assisted
      grafting and ligand exchange, leading to controlled organic-inorganic phase
      separation and an improved maximum power conversion efficiency of 4.1% under AM
      1.5 solar illumination. Our approach can be applied to a wide range of quantum
      dots and polymer hybrids and is compatible with solution processing, thereby
      offering a general scheme for improving the efficiency of nanocrystal hybrid
      solar cells.

PMID- 21859098
TI  - Hydroxycinnamoylmalic acids and their methyl esters from pear (Pyrus pyrifolia
      Nakai) fruit peel.
AB  - Two novel caffeoylmalic acid methyl esters, 2-O-(trans-caffeoyl)malic acid 1
      methyl ester (6) and 2-O-(trans-caffeoyl)malic acid 4-methyl ester (7), were
      isolated from pear (Pyrus pyrifolia Nakai cv. Chuhwangbae) fruit peels. In
      addition, 5 known hydroxycinnamoylmalic acids and their methyl esters were
      identified: 2-O-(trans-coumaroyl)malic acid (1), 2-O-(cis-coumaroyl)malic acid
      (2), 2-O-(cis-coumaroyl)malic acid 1-methyl ester (3), 2-O-(trans-coumaroyl)malic
      acid 1-methyl ester (4), and 2-O-(trans-caffeoyl)malic acid (phaselic acid, 5).
      The chemical structures of these compounds were determined by spectroscopic data
      from ESI MS and NMR. Of all the isolated compounds, five hydroxycinnamoylmalic
      acids and their methyl esters (2-4, 6, 7) were identified in the pear for the
      first time.

PMID- 21859099
TI  - Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT7
      receptor antagonist activity.
AB  - A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT(7) receptor
      antagonists has been studied for their selectivity toward the 5-HT(1A) receptor
      and alpha(1)-adrenoceptor. Several derivatives exhibited high 5-HT(7)/5-HT(1A)
      selectivity, and the key structural factors for reducing undesired alpha(1)
      adrenergic receptor binding have also been identified. Rapid metabolism, a common
      problem within this family of compounds, could be circumvented with appropriate
      substitution patterns on the oxindole carbocycle. Contrary to expectations, none
      of the compounds produced an antidepressant-like action in the forced swimming
      test in mice despite sufficiently high brain concentrations. On the other hand,
      certain analogues showed significant anxiolytic activity in two different animal
      models: the Vogel conflict drinking test in rats and the light-dark test in mice.

PMID- 21859101
TI  - FeTRAM. An organic ferroelectric material based novel random access memory cell.
AB  - Science and technology in the electronics area have always been driven by the
      development of materials with unique properties and their integration into novel
      device concepts with the ultimate goal to enable new functionalities in
      innovative circuit architectures. In particular, a shift in paradigm requires a
      synergistic approach that combines materials, devices and circuit aspects
      simultaneously. Here we report the experimental implementation of a novel
      nonvolatile memory cell that combines silicon nanowires with an organic
      ferroelectric polymer-PVDF-TrFE-into a new ferroelectric transistor architecture.
      Our new cell, the ferroelectric transistor random access memory (FeTRAM) exhibits
      similarities with state-of-the-art ferroelectric random access memories (FeRAMs)
      in that it utilizes a ferroelectric material to store information in a
      nonvolatile (NV) fashion but with the added advantage of allowing for
      nondestructive readout. This nondestructive readout is a result of information
      being stored in our cell using a ferroelectric transistor instead of a capacitor
      the scheme commonly employed in conventional FeRAMs.

PMID- 21859100
TI  - Comparative hydrogen-deuterium exchange for a mesophilic vs thermophilic
      dihydrofolate reductase at 25  degrees C: identification of a single active site
      region with enhanced flexibility in the mesophilic protein.
AB  - The technique of hydrogen-deuterium exchange coupled to mass spectrometry (HDX
      MS) has been applied to a mesophilic (E. coli) dihydrofolate reductase under
      conditions that allow direct comparison to a thermophilic (B. stearothermophilus)
      ortholog, Ec-DHFR and Bs-DHFR, respectively. The analysis of hydrogen-deuterium
      exchange patterns within proteolytically derived peptides allows spatial
      resolution, while requiring a series of controls to compare orthologous proteins
      with only ca. 40% sequence identity. These controls include the determination of
      primary structure effects on intrinsic rate constants for HDX as well as the use
      of existing 3-dimensional structures to evaluate the distance of each backbone
      amide hydrogen to the protein surface. Only a single peptide from the Ec-DHFR is
      found to be substantially more flexible than the Bs-DHFR at 25  degrees C in a
      region located within the protein interior at the intersection of the cofactor
      and substrate-binding sites. The surrounding regions of the enzyme are either
      unchanged or more flexible in the thermophilic DHFR from B. stearothermophilus.
      The region with increased flexibility in Ec-DHFR corresponds to one of two
      regions previously proposed to control the enthalpic barrier for hydride transfer
      in Bs-DHFR [Oyeyemi et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 10074].

PMID- 21859104
TI  - Influence of clay concentration on the gas barrier of clay-polymer nanobrick wall
      thin film assemblies.
AB  - The influence of the clay deposition suspension concentration on gas barrier thin
      films of sodium montmorillonite (MMT) clay and branched polyethylenimine (PEI),
      created via layer-by-layer assembly, was investigated. Films grown with MMT
      suspension concentrations ranging from 0.05 to 2.0 wt % were analyzed for their
      growth as a function of deposited polymer-clay bilayers (BL) and their thickness,
      clay concentration, transparency, nanostructure, and oxygen barrier as a function
      of the suspension concentration. The film thickness doubles and the visible light
      transmission decreases less than 5% as a function of MMT concentration for 20-BL
      films. Atomic force and transmission electron microscope images reveal a highly
      aligned nanobrick wall structure, with quartz crystal microbalance measurements
      revealing a slight increase in the film clay concentration as the MMT suspension
      concentration increases. The oxygen transmission rate (OTR) through these 20-BL
      composites, deposited on a 179 MUm poly(ethylene terephthalate) film, decreases
      exponentially as a function of the MMT clay concentration. A 24-BL film created
      with 2.0 wt % MMT has an OTR below the detection limit of commercial
      instrumentation (<0.005 cc/m(2).day.atm). This study demonstrates an optimal clay
      suspension concentration to use when creating LbL barrier films, which minimizes
      deposition steps and the overall processing time.

PMID- 21859103
TI  - Novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2): crystal structures,
      biochemical activity, and intracellular effects of imidazoacridin-6-ones.
AB  - Imidazoacridin-6-ones are shown to be potent nanomolar inhibitors of the enzyme
      NQO2. By use of computational molecular modeling, a reliable QSAR was
      established, relating inhibitory potency with calculated binding affinity.
      Further, crystal structures of NQO2 containing two of the imidazoacridin-6-ones
      have been solved. To generate compounds with reduced off-target (DNA binding)
      effects, an N-oxide moiety was introduced into the tertiary aminoalkyl side chain
      of the imidazoacridin-6-ones. This resulted in substantially less toxicity in a
      panel of eight cancer cell lines, decreased protein binding, and reduced DNA
      binding and nuclear accumulation. Finally, one of the N-oxides showed potent
      ability to inhibit the enzymatic function of NQO2 in cells, and therefore, it may
      be useful as a pharmacological probe to study the properties of the enzyme in
      vitro and in vivo.

PMID- 21859105
TI  - Electrostatic fields near the active site of human aldose reductase: 2. New
      inhibitors and complications caused by hydrogen bonds.
AB  - Vibrational Stark effect spectroscopy was used to measure electrostatic fields in
      the hydrophobic region of the active site of human aldose reductase (hALR2). A
      new nitrile-containing inhibitor was designed and synthesized, and the X-ray
      structure of its complex, along with cofactor NADP(+), with wild-type hALR2 was
      determined at 1.3 A resolution. The nitrile is found to be in the proximity of
      T113, consistent with a hydrogen bond interaction. Two vibrational absorption
      peaks were observed at room temperature in the nitrile region when the inhibitor
      binds to wild-type hALR2, indicating that the nitrile probe experiences two
      different microenvironments, and these could be empirically separated into a
      hydrogen-bonded and non-hydrogen-bonded population by comparison with the T113A
      mutant, in which a hydrogen bond to the nitrile is not present. Classical
      molecular dynamics simulations based on the structure predict a double-peak
      distribution in protein electric fields projected along the nitrile probe. The
      interpretation of these two peaks as a hydrogen bond formation-dissociation
      process between the probe nitrile group and a nearby amino acid side chain is
      used to explain the observation of two IR bands, and the simulations were used to
      investigate the molecular details of this conformational change. Hydrogen bonding
      complicates the simplest analysis of vibrational frequency shifts as being due
      solely to electrostatic interactions through the vibrational Stark effect, and
      the consequences of this complication are discussed.

PMID- 21859106
TI  - Fucosyltransferases as synthetic tools: glycan array based substrate selection
      and core fucosylation of synthetic N-glycans.
AB  - Two recombinant fucosyltransferases were employed as synthetic tools in the
      chemoenzymatic synthesis of core fucosylated N-glycan structures. Enzyme
      substrates were rapidly identified by incubating a microarray of synthetic N
      glycans with the transferases and detecting the presence of core fucose with four
      lectins and one antibody. Selected substrates were then enzymatically fucosylated
      in solution on a preparative scale and characterized by NMR and MS. With this
      approach the chemoenzymatic synthesis of a series of alpha1,3-, alpha1,6-, and
      difucosylated structures was accomplished in very short time and with high
      yields, which otherwise would have required extensive additional synthetic effort
      and a complete redesign of existing synthetic routes. In addition, valuable
      information was gathered regarding the specificities of the lectins employed in
      this study.

PMID- 21859107
TI  - Mutable Lewis and Bronsted acidity of aluminated SBA-15 as revealed by NMR of
      adsorbed pyridine-15N.
AB  - (1)H and variable-temperature (15)N NMR techniques have been used to study the
      effect of the gradual alumination of SBA-15 on the structure and adsorption
      properties of this mesoporous material. The interpretation of experimental
      spectra suggests that aluminum chlorhydrol most effectively reacts with silica
      surfaces in the confinement of the cavities of rough mesopore walls, instead of
      forming a homogeneous aluminum film. This first leads to a gradual filling of the
      cavities and finally results in aluminum islands on the inner surfaces of
      mesopores. In the sample with a Si/Al atomic ratio of 4.1, up to half of the
      inner surface area of the mesopores is covered with aluminum. The alumination
      produces Bronsted acid sites attributed to silanol groups interacting with
      aluminum but does not affect the proton-donating ability of isolated silanol
      groups. At high Si/Al ratios, the surface contains only one type of Lewis site
      attributed to tetracoordinated aluminum. At lower Si/Al ratios, Lewis acid sites
      with a lower electron-accepting ability appear, as attributed to pentacoordinated
      aluminum. The numerical values of the surface densities of all chemically active
      sites have been estimated after annealing at 420 and 700 K. We were surprised to
      observe that gaseous nitrogen can occupy Lewis acid sites and hinder the
      interaction of the aluminum with any other electron donor. As a result,
      aluminated surfaces saturated with nitrogen do not exhibit any Bronsted or Lewis
      acidity. At room temperature, it takes days before pyridine replaces nitrogen at
      the Lewis acid sites.

PMID- 21859108
TI  - Solvent tuning of a conical intersection: direct experimental verification of a
      theoretical prediction.
AB  - We report an ultrafast study of a merocyanine molecule, whose fluorescence
      lifetime was tuned by changing the solvent's polarity. A recent theoretical
      prediction that the fluorescence lifetime is considerably shortened upon lowering
      the polarity of the solvent, due to tuning of the conical intersection
      properties, is fully confirmed (Xu et al. J. Phys. Chem. A 2009, 113, 9779-9791).
      This constitutes a direct measurement of a previously predicted tunable property
      of a conical intersection.

PMID- 21859109
TI  - Pore-spanning lipid membrane under indentation by a probe tip: a molecular
      dynamics simulation study.
AB  - We study the indentation of a free-standing lipid membrane suspended over a
      nanopore on a hydrophobic substrate by means of molecular dynamics simulations.
      We find that in the course of indentation the membrane bends at the point of
      contact and the fringes of the membrane glide downward intermittently along the
      pore edges and stop gliding when the fringes reach the edge bottoms. The bending
      continues afterward, and the large strain eventually induces a phase transition
      in the membrane, transformed from a bilayered structure to an interdigitated
      structure. The membrane is finally ruptured when the indentation goes deep
      enough. Several local physical quantities in the pore regions are calculated,
      which include the tilt angle of lipid molecules, the nematic order, the included
      angle, and the distance between neighboring lipids. The variations of these
      quantities reveal many detailed, not-yet-specified local structural transitions
      of lipid molecules under indentation. The force-indentation curve is also studied
      and discussed. The results make a connection between the microscopic structure
      and the macroscopic properties and provide deep insight into the understanding of
      the stability of a lipid membrane spanning over nanopore.

PMID- 21859110
TI  - Complete debromination of tetra- and penta-brominated diphenyl ethers by a
      coculture consisting of dehalococcoides and desulfovibrio species.
AB  - Polybrominated diphenyl ethers (PBDEs) are widespread global contaminants due to
      their extensive usage as flame retardants. Among the 209 PBDE congeners, tetra
      brominated diphenyl ether (tetra-BDE) (congener 47) and penta-BDEs (congeners 99
      and 100) are the most abundant, toxic, and bioaccumulative congeners in the
      environment. However, little is known about microorganisms that carry out
      debromination of these congeners under anaerobic conditions. In this study, we
      describe a coculture GY2 consisting of Dehalococcoides and Desulfovibrio spp.,
      which is capable of debrominating ~1180 nM of congeners 47, 99, and 100 (88-100%
      removal) to the nonbrominated diphenyl ether at an average rate of 36.9, 19.8,
      and 21.9 nM day(-1), respectively. Ortho bromines are preferentially removed
      during the debromination process. The growth of Dehalococcoides links tightly
      with PBDE debromination, with an estimated growth yield of 1.99 * 10(14) cells
      per mole of bromide released, while the growth of Desulfovibrio could be
      independent of PBDEs. The growth-coupled debromination suggests that
      Dehalococcoides cells in the coculture GY2 are able to respire on PBDEs. Given
      the ubiquity and recalcitrance of the tetra- and penta-BDEs, complete
      debromination of these congeners to less toxic end products (e.g. diphenyl ether)
      is important for the restoration of PBDE-contaminated environments.

PMID- 21859111
TI  - Confinement of photopolymerization and solidification with radiation pressure.
AB  - Controlling chemical reactions within a small space is a significant issue in
      chemistry, and methods to induce reactions within a desired position have various
      potential applications. Here we demonstrate localized, efficient
      photopolymerization by radiation pressure. We induced a one-photon UV
      polymerization of liquid acrylate solutions in the optical-trapping potential of
      a focused near-IR (NIR) laser beam, leading to the confinement of solidification
      to a minute space with dimensions smaller or equal to one-fifth of the wavelength
      of the NIR laser. Our approach can produce solidification volumes smaller than
      those achievable with conventional one-photon polymerization, thus enabling the
      production of tiny polymeric structures that are smaller than the diffraction
      limit of the trapping light. This is the first demonstration of a radiation
      pressure effect on a photochemical reaction.

PMID- 21859112
TI  - Reversibility of the adsorption of lysozyme on silica.
AB  - A central paradigm that underpins our understanding of the interaction of
      proteins with solid surfaces is that protein adsorption leads to changes in
      secondary structure. The bound proteins tend to denature, and these non-native,
      adsorbed structures are likely stabilized through the loss of alpha-helices with
      the concomitant formation of intermolecular beta-sheets. The goal of this work is
      to critically assess the impact this behavior has on protein desorption, where
      irreversible conformational changes might lead to protein aggregation or result
      in other forms of instability. The adsorption, desorption, and structural
      transitions of lysozyme are examined on fumed silica nanoparticles as a function
      of the amount of protein adsorbed. Surprisingly, the data indicate not only that
      adsorption is reversible but also that protein desorption is predictable in a
      coverage-dependent manner. Additionally, there is evidence of a two-state model
      which involves exchange between a native-like dissolved state and a highly
      perturbed adsorbed state. Since the in situ circular dichroism (CD) derived
      secondary structures of the adsorbed proteins are essentially unaffected by
      changes in surface coverage, these results are not consistent with previous
      claims that surface-induced denaturation is coverage dependent. Inspired by
      results from homopolymer adsorption experiments, we speculate that more local
      descriptors, such as the number of amino acids per chain that are physically
      adsorbed on the surface, likely control the desorption process.

PMID- 21859113
TI  - Smart heterostructures for tailoring the optical properties of photochromic
      hybrid organic-inorganic polyoxometalates.
AB  - A new concept of photoresponsive composites has been elaborated by intimately
      connecting a Photochromic Phase (PP),
      (H(2)DABCO)(2)(HDMA)(0.5)Na(0.75)(H(3)O)(0.75)[Mo(8)O(27)].3H(2)O (1), with a
      second hybrid organic-inorganic molybdate material,
      (H(2)DABCO)(HDABCO)[Fe(OH)(6)Mo(6)O(18)].4H(2)O (2) acting as an Oxidation
      Catalytic Phase (OCP) toward the former once photoexcited. The association of
      both the PP and the OCP in the composite drastically improves the bleaching
      process of the PP alone because of efficient electronic transfers through the OCP
      PP interface without affecting significantly its photoinduced color change
      characteristic. Two OCP-PP composites with different PP weight percents have been
      obtained by associating 1 with 2. The optical properties of these composites
      before and after UV irradiation have been investigated by Diffuse Reflectance
      Spectroscopy, and the strong impact of the OCP on the fading kinetics of the PP
      has been clearly highlighted.

PMID- 21859114
TI  - Homochiral frameworks formed by reactions of lanthanide ions with a chiral
      antimony tartrate secondary building unit.
AB  - A chiral cluster compound, dipotassium bis(MU-tartrato)diantimony(III),
      K(2)Sb(2)L(2) (H(4)L = L-tartaric acid), was used as a secondary building unit to
      react with lanthanide ions. Three series of homochiral coordination compounds
      were obtained: 0D [La(H(2)L)(H(2)O)(4)](2)[Sb(2)L(2)].7H(2)O (0D-La), 1D
      Ln(Sb(2)L(2))(H(2)O)(5)(NO(3)).H(2)O (1D-Ln) (Ln = La-Lu or Y, expect Pm), 2D(I)
      [(Ln(H(2)O)(5))(2)(Sb(2)L(2))(3)].5H(2)O (2D(I)-Ln) (Ln = La, Ce, Pr), and 2D(II)
      [(La(H(2)O)(5))(2)(Sb(2)L(2))(3)].6H(2)O (2D(II)-La). Single-crystal X-ray
      diffraction studies indicated that 0D-La crystallizes in space group P1, and the
      structure contains isolated Sb(2)L(2)(2-) units located between chains of
      composition La(H(2)L)(H(2)O)(4). The series of 1D-Ln compounds is isostructural
      and crystallizes in space group P2(1)2(1)2(1). In the structure, Sb(2)L(2)(2-)
      units are coordinated to two Ln ions by two out of the four free tartrate oxygen
      atoms to form a linear chain. To the best of our knowledge, this is the first
      example of a homochiral structure that can be formed for the whole lanthanide
      series. In the 2D(I)-Ln structure series, which crystallizes in space group
      P2(1), the Sb(2)L(2)(2-) units have two distinct coordination modes: one is the
      same as that found in the 1D structure, while in the other all four free tartrate
      oxygen atoms are coordinated to four Ln ions in a very distorted tetrahedral
      arrangement. The connectivity between Sb(2)L(2)(2-) secondary units and LnO(9)
      polyhedra gives rise to infinite layers. 2D(II)
      [(La(H(2)O)(5))(2)(Sb(2)L(2))(3)].6H(2)O, which crystallizes in space group C2,
      has a similar network to the 2D(I)-Ln compounds. The trends in lattice
      parameters, bond lengths, and ionic radii in the 1D-Ln series were analyzed to
      show the effect of the lanthanide contraction.

PMID- 21859115
TI  - Kinetic resolution of beta-lactams via enantioselective N-acylation.
AB  - Enantioselective N-acylation of 4-aryl-beta-lactams in the presence of acyl
      transfer catalyst Cl-PIQ provides an effective method for their non-enzymatic
      kinetic resolution.

PMID- 21859116
TI  - Arylamine-based dyes for p-type dye-sensitized solar cells.
AB  - New arylamine-based sensitizers for p-type dye-sensitized solar cells (DSSCs)
      have been synthesized and used for p-type DSSCs. The best conversion efficiency
      reaches ~0.1%. Sensitizers with two anchoring carboxylic acids lead to higher
      open-circuit voltages, short-circuit currents, and energy conversion
      efficiencies.

PMID- 21859117
TI  - Performance evaluation of gas chromatography-atmospheric pressure chemical
      ionization-time-of-flight mass spectrometry for metabolic fingerprinting and
      profiling.
AB  - Gas chromatography-atmospheric-pressure chemical ionization-time-of-flight mass
      spectrometry (GC-APCI-TOFMS) was compared to GC * GC-electron ionization (EI)
      TOFMS, GC-EI-TOFMS, GC-chemical ionization (CI)-quadrupole mass spectrometry
      (qMS), and GC-EI-qMS in terms of reproducibility, dynamic range, limit of
      detection, and quantification using a mix of 43 metabolites and 12 stable isotope
      labeled standards. Lower limits of quantification for GC-APCI-TOFMS ranged
      between 0.06 and 7.81 MUM, and relative standard deviations for calibration
      replicates were between 0.4% and 8.7%. For all compounds and techniques, except
      in four cases, R(2) values were above 0.99. Regarding limits of quantification,
      GC-APCI-TOFMS was inferior to only GC * GC-EI-TOFMS, but outperformed all other
      techniques tested. GC-APCI-TOFMS was further applied to the metabolic
      fingerprinting of two Escherichia coli strains. Of 45 features that differed
      significantly (false discovery rate < 0.05) between the strains, 25 metabolites
      were identified through highly accurate and reproducible (Deltam +/- SD below 5
      mDa over m/z 190-722) mass measurements. Starting from the quasimolecular ion,
      six additional metabolites were identified that had not been found in a previous
      study using GC * GC-EI-TOFMS and an EI mass spectral library for identification
      purposes. Silylation adducts formed in the APCI source assisted the
      identification of unknown compounds, as their formation is structure-dependent
      and is not observed for compounds lacking a carboxylic group.

PMID- 21859118
TI  - Electrochemical impedance study of GaAs surface charge modulation through the
      deprotonation of carboxylic acid monolayers.
AB  - Modifications to the space charge region of p+ and p-GaAs due to surface charge
      modulation by the pH-induced deprotonation of bound carboxylic acid terminal
      monolayers were studied by electrochemical impedance spectroscopy and correlated
      to flat-band potential measurements from Mott-Schottky plots. We infer that the
      negative surface dipole formed on GaAs due to monolayer deprotonation causes an
      enhancement of the downward interfacial band bending. The space charge layer
      modifications were correlated to intermolecular electrostatic interactions and
      semiconductor depletion characteristics.

PMID- 21859119
TI  - Enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes.
AB  - An enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes via
      a Knoevenagel/Pinner/Friedel-Crafts reaction of salicylaldehyde, malononitrile,
      and indole is presented. Moderate to good yields (up to 89%) and high
      enantioselectivities (up to 90% ee) were obtained with an N,N'-dioxide-Zn(II)
      complex as the catalyst. This strategy provides an efficient and convenient
      method to access enantiomerically enriched 2-amino-4H-chromene derivatives.

PMID- 21859120
TI  - Probing the lithium ion storage properties of positively and negatively carved
      silicon.
AB  - Here, we report Si pillar and well arrays as tailored electrode materials for
      advanced Li ion storage devices. The well-ordered and periodic morphologies were
      formed on a Si electrode thin film via laser interference lithography followed by
      a dry etch process. Two different patterns of negatively or positively carved Si
      electrodes exhibited highly improved cycle performance as a consequence of the
      enlarged surface area and the nanoscale pattern effects. The Si well arrays
      showed the highest energy density, rate capability, and cycling retention among
      the prepared Si electrodes. This tailored electrode platform demonstrates that
      these design principles could be applied to future developments in Si electrodes.

PMID- 21859121
TI  - Patterning functional materials using channel diffused plasma-etched self
      assembled monolayer templates.
AB  - A simple and cost-effective methodology for large-area micrometer-scale
      patterning of a wide range of metallic and oxidic functional materials is
      presented. Self-assembled monolayers (SAM) of alkyl thiols on Au were
      micropatterned by channel-diffused oxygen plasma etching, a method in which
      selected areas of SAM were protected from plasma oxidation via a soft
      lithographic stamp. The patterned SAMs were used as templates for site-selective
      electrodeposition, electroless deposition and solution-phase deposition of
      functional materials such as ZnO, Ni, Ag thin films, and ZnO nanowires. The
      patterned SAMs and functional materials were characterized by scanning electron
      microscopy (SEM), X-ray diffraction (XRD), atomic force microscopy (AFM), and
      tunneling AFM (TUNA).

PMID- 21859122
TI  - PAH molecular diagnostic ratios applied to atmospheric sources: a critical
      evaluation using two decades of source inventory and air concentration data from
      the UK.
AB  - Molecular diagnostic ratios (MDRs)-the ratios of defined pairs of individual
      compounds-have been widely used as markers of different source categories of
      polycyclic aromatic hydrocarbons (PAHs). However, it is well-known that
      variations in combustion conditions and environmental degradation processes can
      cause substantial variability in the emission and degradation of individual
      compounds, potentially undermining the application of MDRs as reliable source
      apportionment tools. The United Kingdom produces a national inventory of
      atmospheric emissions of PAHs, and has an ambient air monitoring program at a
      range of rural, semirural, urban, and industrial sites. The inventory and the
      monitoring data are available over the past 20 years (1990-2010), a time frame
      that has seen known changes in combustion type and source. Here we assess 5 MDRs
      that have been used in the literature as source markers. We examine the spatial
      and temporal variability in the ratios and consider whether they are responsive
      to known differences in source strength and types between sites (on rural-urban
      gradients) and to underlying changes in national emissions since 1990. We
      conclude that the use of these 5 MDRs produces contradictory results and that
      they do not respond to known differences (in time and space) in atmospheric
      emission sources. For example, at a site near a motorway and far from other
      evident emission sources, the use of MDRs suggests "non-traffic" emissions. The
      ANT/(ANT + PHE) ratio is strongly seasonal at some sites; it is the most
      susceptible MDR to atmospheric processes, so these results illustrate how
      weathering in the environment will undermine the effectiveness of MDRs as markers
      of source(s). We conclude that PAH MDRs can exhibit spatial and temporal
      differences, but they are not valid markers of known differences in source
      categories and type. Atmospheric sources of PAHs in the UK are probably not
      dominated by any single clear and strong source type, so the mixture of PAHs in
      air is quickly "blended" away from the influence of the few major point sources
      which exist and further weathered in the environment by atmospheric reactions and
      selective loss processes.

PMID- 21859123
TI  - Chemistry of trans-resveratrol with singlet oxygen: [2+2] addition, [4+2]
      addition, and formation of the phytoalexin moracin M.
AB  - Resveratrol (1) reacts with singlet oxygen by two major pathways: A [2+2]
      cycloaddition forming a transient dioxetane that cleaves into the corresponding
      aldehydes and a [4+2] cycloaddition forming an endoperoxide that, upon heating,
      undergoes a rearrangement to moracin M. The rate constant by which singlet oxygen
      is removed by 1 (k(T)) was determined by time-resolved infrared luminescence
      spectroscopy to be 1.5 * 10(6) M(-1) sec(-1) in CD(3)OD, smaller than previously
      reported values. Chemical reaction accounts for ca. 25% of k(T).

PMID- 21859124
TI  - Measurements of heavy-atom isotope effects using 1H NMR spectroscopy.
AB  - A novel method for measuring heavy-atom KIEs for magnetically active isotopes
      using (1)H NMR is presented. It takes advantage of the resonance split of the
      protons coupled with the heavy atom in the (1)H spectrum. The method is validated
      by the example of the (13)C-KIE on the hydroamination of styrene with aniline,
      catalyzed by phosphine-ligated palladium triflates.

PMID- 21859125
TI  - Effect of dexamethasone on gliosis, ischemia, and dopamine extraction during
      microdialysis sampling in brain tissue.
AB  - Microdialysis sampling of the brain is an analytical technique with numerous
      applications in neuroscience and the neurointensive care of brain-injured human
      patients. Even so, implanting microdialysis probes into brain tissue causes a
      penetration injury that triggers gliosis (the activation and proliferation of
      glial cells) and ischemia (the interruption of blood flow). Thus, the probe
      samples injured tissue. Mitigating the effects of the penetration injury might
      refine the technique. The synthetic glucocorticoid dexamethasone is a potent anti
      inflammatory and immunosuppressant substance. We performed microdialysis in the
      rat brain for 5 days, with and without dexamethasone in the perfusion fluid (10
      MUM for the first 24 h and 2 MUM thereafter). On the first and fourth day of the
      perfusion, we performed dopamine no-net-flux measurements. On the fifth day, we
      sectioned and stained the brain tissue and examined it by fluorescence
      microscopy. Although dexamethasone profoundly inhibited gliosis and ischemia
      around the probe tracks it had only modest effects on dopamine no-net-flux
      results. These findings show that dexamethasone is highly effective at
      suppressing gliosis and ischemia but is limited in its neuroprotective activity.

PMID- 21859127
TI  - Binding of hydrophobic fluorinated bisphenol A to large unilamellar vesicles of
      egg phosphatidylcholine.
AB  - The kinetics of membrane binding and dissociation of fluorinated bisphenol A
      (FBPA, (CF(3))(2)C(C(6)H(4)OH)(2)) is quantified by 1D (19)F NMR spectra in situ.
      Although the bound and free components are in fast exchange, the rate constants
      and bound fraction is nonetheless determined from an analysis of the spectra. The
      analysis relies on the expression of 1D NMR signal intensity by a set of Bloch
      equations with exchange terms. The time span of the binding and dissociation of
      hydrophobic FBPA to large unilamellar vesicles of egg phosphatidylcholine (EPC)
      is 10(-3) to 10(-2) s. The rates of FBPA binding and dissociation are kept
      constant per EPC molecule even at different concentrations of the vesicle. The
      free energy of FBPA transfer is -20 +/- 2 kJ/mol at 303 K. The process is entropy
      driven. The efficiency of FBPA transfer is enhanced by a factor of 7 * 10(4), as
      compared with the hydrophilic 5-fluorouracil.

PMID- 21859128
TI  - Inorganic/organic (SiO2)/PEO hybrid electrospun nanofibers produced from a
      modified sol and their surface modification possibilities.
AB  - Ceramic silica (SiO(2)) hybrid nanofibers were prepared by electrospinning of
      solutions containing biocompatible polymer and modified silica precursors. The
      new hybrid nanofibers are based on polyethylene oxide (PEO) and a new solution of
      modified sol-gel particles of mixture containing tetraethoxysilane (TEOS) and 3
      glycidyloxypropyltriethoxysilane (GPTEOS) in a weight ratio of 3:1. Adding high
      molecular-weight PEO into the silica sol is found to enhance the formation of the
      silica nanofibers and leads to reduce the water-soluble carrying polymer down to
      1.2%wt. Transmission electron microscopy (TEM) and attenuated total reflection
      fourier transformation infrared ATR-FTIR measurements are suggested that PEO is
      encapsulated by the silica component. This excellent formulation renders
      electrospinning of SiO(2) a robust process for an easy production of controllable
      silicate nanofibrous matrices. For instance, nanofibers with average diameter
      down to 400 nm are accessible by varying the weight ratio between the polymer and
      the inorganic precursor. These are reduced to 120 nm after the pyrolysis process.
      Moreover, the surface of the nanofibers could be easily modified, either by
      Al(3+) leading to aluminium silicate coatings, or by incorporation of Ca(2+) ions
      and subsequent bioactive hydroxyl carbonate apatite (HAP) formation. These hybrid
      silica nanofibers are possess a unique collective properties can have a great
      impact either in high-temperature reinforced materials and filtration or in
      biomedical applications such as in dentistry and bone tissue engineering.

PMID- 21859129
TI  - Two- and three-dimensional silver(I)-organic networks generated from mono- and
      dicarboxylphenylethynes.
AB  - Three phenylethynes bearing methyl carboxylate (HL1), monocarboxylate (H(2)L2),
      and dicarboxylate (H(2)L3) groups were utilized as ligands to synthesize a new
      class of organometallic silver(I)-ethynide complexes as bifunctional building
      units to assemble silver(I)-organic networks. X-ray crystallographic studies
      revealed that in [Ag(2)(L1)(2).AgNO(3)](infinity) (1) (L1= 4
      C(2)C(6)H(4)CO(2)CH(3)), one ethynide group interacts with three silver ions to
      form a complex unit. These units aggregate by sharing silver ions with the other
      three units to afford a silver column, which are further linked through
      argentophilic interaction to generate a two-demensional (2D) silver(I) network.
      In [Ag(2)(L2).3AgNO(3).H(2)O](infinity) (2) (L2 = 4-CO(2)C(6)H(4)C(2)), the
      ethynide group coordinates to four silver ions to form a building unit
      (Ag(4)C(2)C(6)H(4)CO(2)), which interacts through silver(I)-carboxylate
      coordination bonds to generate a wave-like 2D network and is subsequently
      connected by nitrate anions as bridging ligands to afford a three-demensional
      (3D) network. In [Ag(3)(L3).AgNO(3)](infinity) (3) (L3 = 3,5
      (CO(2))(2)C(6)H(3)C(2)), the building unit (Ag(4)C(2)C(6)H(3)(CO(2))(2))
      aggregates to form a dimer [Ag(8)(L3)(2)] through argentophilic interaction. The
      dimeric units interact through silver(I)-carboxylate coordination bonds to
      directly generate a 3D network. The obtained results showed that as a building
      unit, silver(I)-ethynide complexes bearing carboxylate groups exhibit diverse
      binding modes, and an increase in the number of carboxylate groups in the
      silver(I)-ethynide complex unit leads to higher level architectures. In the solid
      state, all of the complexes (1, 2, and 3) are photoluminescent at room
      temperature.

PMID- 21859126
TI  - N-O chemistry for antibiotics: discovery of N-alkyl-N-(pyridin-2-yl)hydroxylamine
      scaffolds as selective antibacterial agents using nitroso Diels-Alder and ene
      chemistry.
AB  - The discovery, syntheses, and structure-activity relationships (SAR) of a new
      family of heterocyclic antibacterial compounds based on N-alkyl-N-(pyridin-2
      yl)hydroxylamine scaffolds are described. A structurally diverse library of ~100
      heterocyclic molecules generated from Lewis acid-mediated nucleophilic ring
      opening reactions with nitroso Diels-Alder cycloadducts and nitroso ene reactions
      with substituted alkenes was evaluated in whole cell antibacterial assays.
      Compounds containing the N-alkyl-N-(pyridin-2-yl)hydroxylamine structure
      demonstrated selective and potent antibacterial activity against the Gram
      positive bacterium  Micrococcus luteus  ATCC 10240 (MIC(90) = 2.0 MUM or 0.41
      MUg/mL) and moderate activity against other Gram-positive strains including
      antibiotic resistant strains of  Staphylococcus aureus  (MRSA) and  Enterococcus
      faecalis  (VRE). A new synthetic route to the active core was developed using
      palladium-catalyzed Buchwald-Hartwig amination reactions of N-alkyl-O-(4
      methoxybenzyl)hydroxylamines with 2-halo-pyridines that facilitated SAR studies
      and revealed the simplest active structural fragment. This work shows the value
      of using a combination of diversity-oriented synthesis (DOS) and parallel
      synthesis for identifying new antibacterial scaffolds.

PMID- 21859130
TI  - Effect of cellulose acetate butyrate microencapsulated ammonium polyphosphate on
      the flame retardancy, mechanical, electrical, and thermal properties of
      intumescent flame-retardant ethylene-vinyl acetate copolymer/microencapsulated
      ammonium polyphosphate/polyamide-6 blends.
AB  - Ammonium polyphosphate (APP), a widely used intumescent flame retardant, has been
      microencapsulated by cellulose acetate butyrate with the aim of enhancing the
      water resistance of APP and the compatibility between the ethylene-vinyl acetate
      copolymer (EVA) matrix and APP. The structure of microencapsulated ammonium
      polyphosphate (MCAPP) was characterized by Fourier transform infrared
      spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron
      microscopy (SEM), and water contact angle (WCA). The flame retadancy and thermal
      stability were investigated by a limiting oxygen index (LOI) test, UL-94 test,
      cone calorimeter, and thermogravimetric analysis (TGA). The WCA results indicated
      that MCAPP has excellent water resistance and hydrophobicity. The results
      demonstrated that MCAPP enhanced interfacial adhesion, mechanical, electrical,
      and thermal stability of the EVA/MCAPP/polyamide-6 (PA-6) system. The
      microencapsulation not only imparted EVA/MCAPP/PA-6 with a higher LOI value and
      UL-94 rating but also could significantly improve the fire safety. Furthermore,
      the microencapsulated EVA/MCAPP/PA-6 composites can still pass the UL-94 V-0
      rating after treatment with water for 3 days at 70  degrees C, indicating
      excellent water resistance. This investigation provides a promising formulation
      for the intumescent flame retardant EVA with excellent properties.

PMID- 21859131
TI  - Using the meniscus in a capillary for small volume contact angle measurement in
      biochemical applications.
AB  - The contact angle is a sensitive parameter often used to define wettability. With
      the increasing movement toward smaller liquid volumes in many biochemical
      applications, a key challenge lies in how to perform measurements in the retainer
      holding the reagent for rapid evaluation and limited material loss. Here, we
      report a simple and robust method to determine the contact angle of small volumes
      using the microscopic imaging of a capillary meniscus that requires only the
      radius and meniscus height information. An error analysis of the measurement
      finds the method to be highly accurate. We also uncovered that illumination
      delivered from the liquid end of the capillary lights up the interface, thereby
      facilitating the measurement.

PMID- 21859132
TI  - Micellization of monomeric and poly-omega-methacryloyloxyundecyltrimethylammonium
      surfactants.
AB  - We have used small-angle neutron scattering to study how micelle morphology of
      the tail-polymerizable surfactants MUTAB and MUTAC (omega
      methacryloyloxyundecyltrimethylammonium bromide and chloride) is affected by
      classic self-assembly modifiers such as temperature changes, salt addition, and
      counterion exchange, as a function of their conversion from monomer into polymer
      amphiphile in aqueous solution. Contrary to common assumptions about polymerized
      surfactants, these systems remain in dynamic equilibrium under all conditions
      examined and at all conversions (except for a small amount of high-molecular
      weight precipitation by MUTAC). Counterintuitively, the polymerized methacrylate
      backbone has little influence on aggregate morphology, except for the formation
      of rod-like mixed micelles of polymerized and unpolymerized surfactant at
      intermediate conversions. The addition of salt produces a transition to rod-like
      micelles at all conversions except in the unpolymerized surfactant, which has
      some characteristics of an asymmetric bolaform surfactant and retains its
      spheroidal geometry under almost all conditions.

PMID- 21859133
TI  - Dielectric analysis of micelles and microemulsions formed in a hydrophilic ionic
      liquid. I. Interaction and percolation.
AB  - Dielectric measurements were carried out on binary mixtures of Triton X-100 (TX
      100, a nonionic surfactant with a polyoxyethylene chain) and 1-butyl-3
      methylimidazolium tetrafluoroborate ([bmim][BF(4)], a hydrophilic ionic liquid),
      and [bmim][BF(4)]/TX-100/cyclohexane microemulsions in a wide frequency range to
      study the molecular interaction and percolation in these systems. Striking
      dielectric relaxations were observed, and the dc conductivity data were obtained
      from the measured total dielectric loss spectra. The interaction between TX-100
      and [bmim][BF(4)] is estimated by analyzing the dc conductivity of TX
      100/[bmim][BF(4)] solutions in light of the Bruggeman's effective medium
      approximation, which indicates that spherical micelles are formed when the TX-100
      volume fraction is below 48% and the number of cations associated with every TX
      100 molecule is eight. For IL-oil microemulsions, both the dependence of dc
      conductivity and the permittivity (for fixed frequency) on cyclohexane
      concentration were used to identify the oil-in-IL, bicontinuous, and IL-in-oil
      microregions. Both the conduction and dielectric relaxation behavior suggest that
      a static percolation occurs in this hydrophilic IL microemulsion.

PMID- 21859135
TI  - Zipping up: cooperativity drives the synthesis of graphene nanoribbons.
AB  - We investigate the cooperative effects controlling the synthesis of a graphene
      nanoribbon on the Au(111) surface starting from an anthracene polymer using
      density functional calculations including van der Waals interactions. We focus on
      the high-temperature cyclodehydrogenation step of the reaction and find that the
      reaction proceeds by simultaneously transferring two H-atoms from the anthracene
      units to the Au surface, leaving behind a C-C bond in the process. This step is
      significantly more favorable than the three other potential reaction paths.
      Moreover, we find that successive dehydrogenations proceed from one end of the
      polyanthracene and propagate step-by-step through the polymer in a domino-like
      fashion.

PMID- 21859134
TI  - A new two-state polymer folding model and its application to alpha-helical
      polyalanine.
AB  - A new two-state polymer folding model is proposed, in which the folding of a
      stiff helical polymer is enabled by allowing for short sequences of coils
      connecting shorter and separated helices. The folding is driven by short-range
      attraction energy among stacked helices and is opposed by the free-energy cost of
      forming coils from helical monomers. Principal outcomes of the model are
      equilibrium distribution of the number of helices and their length in helical
      polymers. The proposed model is applied to alpha-helical polyalanine. The
      distribution of the number of alpha-helices as a function of number of alanine
      residues is fitted to the corresponding result from molecular dynamics simulation
      employing an all-atom potential model with very good agreement. The influence and
      significance of the fitting parameters and possible use of the two-state folding
      model are discussed.

PMID- 21859136
TI  - Validating affinities for ion-lipid association from simulation against
      experiment.
AB  - Understanding biological membranes at physiological conditions requires
      comprehension of the interaction of lipid bilayers with sodium and potassium
      ions. These cations are adsorbed at palmitoyl-oleoyl-phosphatidylcholine (POPC)
      bilayers as indicated from previous studies. Here we compare the affinity of
      Na(+) and K(+) for POPC in molecular dynamics (MD) simulations with recent data
      from electrophoresis experiments and isothermal calorimetry (ITC) at neutral pH.
      NaCl and KCl were described using GROMOS or parameters matching solution
      activities on the basis of Kirkwood-Buff theory (KBFF), and K(+) was also
      described using parameters by Dang et al., all in conjunction with the Berger
      parameters for the lipids and the SPC water model. Apparent binding constants of
      GROMOS-Na(+) and KBFF-K(+) are the same within error and in good agreement with
      values from ITC. Although these force fields yield the same number of bound ions
      per number of lipids for Na(+) and K(+), they give a larger number of Na(+) ions
      per surface area compared to K(+), in agreement with the electrophoresis
      experiments, because Na(+) causes a stronger reduction in the area per lipid than
      K(+). The intrinsic binding constants, on the other hand, are reproduced by Dang
      K(+) but overestimated by GROMOS-Na(+) and KBFF-K(+). That no ion force field
      reproduces the intrinsic and the apparent binding constant simultaneously arises
      from the fact that in MD simulations, implicitly meant to mimic neutral pH, pure
      PC is usually modeled with zero surface charge. In contrast, POPC at neutral
      conditions in experiment carries a low but significant negative surface charge
      and is uncharged only at acidic pH as indicated from electrophoretic mobilities.
      Implications for future simulation and experimental studies are discussed.

PMID- 21859138
TI  - Evidence for self-association of a miniaturized version of agrin from
      hydrodynamic and small-angle X-ray scattering measurements.
AB  - Hydrodynamic studies of miniagrin indicate a molar mass that is 20% larger than
      the value calculated from the sequence of this genetically engineered protein.
      Consistent with this finding is the negative sign and also the magnitude of the
      second virial coefficient obtained from small-angle X-ray scattering
      measurements. The inference that miniagrin reversibly self-associates is
      confirmed by a sedimentation equilibrium study that yields an equilibrium
      constant of 0.24 L/g for a putative monomer-dimer interaction. Finally, Guinier
      analysis of the small-angle X-ray scattering (SAXS) results yields concentration
      dependent values for the radius of gyration that may be described by the monomer
      dimer model and respective R(g) values of 40 and 105 A for the monomeric and
      dimeric miniagrin species. Although intermolecular protein interactions are
      endemic in the events leading to acetylcholine receptor aggregation by agrin, the
      matrix proteoglycan of which miniagrin is a miniaturized model, this
      investigation raises the possibility that agrin may itself self-associate.

PMID- 21859139
TI  - Simulated glass transition of poly(ethylene oxide) bulk and film: a comparative
      study.
AB  - Stepwise cooling molecular dynamics (MD) simulations have been carried out on the
      bulk and film models for poly(ethylene oxide) (PEO) to understand glass
      transition of amorphous polymer films. Three types of properties--density,
      energy, and dynamics--are computed and plotted against the temperature for the
      two systems. It has been confirmed that all these properties can reveal glass
      transition in both PEO bulk and film systems. All the determined glass transition
      temperatures (T(g)'s) drop in the same order of magnitude to the experimental
      data available. Among various methods, the T(g)'s obtained from the density and
      energy data are close to each other if the same space regions are defined, which
      can suggest the same free volume theory, and dynamic T(g)'s obtained from mean
      squared displacements (MSDs) are highest, which can suggest the kinetic theory
      for structural relaxation. Consistently, all these T(g)'s obtained using
      different methods show that the T(g)'s of PEO film are lower than those of PEO
      bulk. The free surface layers of polymer films dictate this offset.

PMID- 21859137
TI  - Evaluation of the synthesis of sialic acid-PAMAM glycodendrimers without the use
      of sugar protecting groups, and the anti-HIV-1 properties of these compounds.
AB  - A study was undertaken to evaluate the feasibility of synthesizing six sialic
      acid-PAMAM glycodendrimers using unprotected sialic acid in as few as 1-4 steps
      using two different reaction pathways, and to assess the sulfated derivatives for
      anti-HIV activity. The syntheses were accomplished through either the direct
      attachment of the sialic acid carboxyl group to amine-terminated PAMAM (a
      divergent-like approach) using BOP coupling, or by first reacting sialic acid
      with a polar bifunctional spacer molecule, attaching the sugar-linker to carboxy
      terminated PAMAM (a convergent-like approach), and again using BOP-mediated
      coupling reactions. It was hypothesized that the latter approach would be the
      most successful method, as any steric congestion between the sialic acid and the
      PAMAM would be minimized using an intervening polar linker. However, the
      divergent-like synthesis proved to be the superior method, resulting in 11.4%,
      14%, and 28% of the fully substituted generations 0, 1, and 2 sialic acid-PAMAM
      conjugates, respectively, as compared to 6.4% of only the generation -0.5 sialic
      acid-linker-PAMAM conjugate for the convergent-like method. Upon sulfation of the
      four glycodendrimers, binding capabilities to the recombinant HIV protein, gp120,
      were assessed using an ELISA assay. Compounds that showed promising binding
      characteristics were then further assessed for inhibition of HIV-1 infection
      using a well-characterized luciferase reporter gene neutralization assay. The
      generation 2 sulfated sialic acid-PAMAM glycodendrimer, sulfo-6, bearing 16
      sialic acids with 11 sulfate groups incorporated at 4.03% sulfur content by
      weight, was found to inhibit all four HIV-1 strains tested in the low micromolar
      range.

PMID- 21859140
TI  - Quantitation of 7-ethylguanine in leukocyte DNA from smokers and nonsmokers by
      liquid chromatography-nanoelectrospray-high resolution tandem mass spectrometry.
AB  - There is considerable evidence for the exposure of humans to an unknown
      ethylating agent, and some studies indicate that cigarette smoking may be one
      source of this exposure. Therefore, we have developed a liquid chromatography
      nanoelectrospray-high resolution tandem mass spectrometry-selected reaction
      monitoring (LC-NSI-HRMS/MS-SRM) method for the analysis of 7-ethyl-Gua in human
      leukocyte DNA, a readily available source of DNA. [(15)N(5)]7-Ethyl-Gua was used
      as the internal standard. Leukocyte DNA was isolated and treated by thermal
      neutral hydrolysis. The hydrolysate was partially purified by solid-phase
      extraction. The fraction containing 7-ethyl-Gua was analyzed by LC-NSI-HRMS/MS
      SRM using the transition m/z 180 [M + H](+)-> m/z 152.05669 [Gua + H](+) for 7
      ethyl-Gua and m/z 185 -> m/z 157.04187 for the internal standard. The detection
      limit was approximately 10 amol on column, while the limit of quantitation was
      about 8 fmol/MUmol Gua starting with 180 MUg DNA (corresponding to 36 MUg DNA on
      column). Leukocyte DNA samples from 30 smokers and 30 nonsmokers were analyzed.
      Clear peaks for 7-ethyl-Gua and the internal standard were observed in most of
      the samples. The mean (+/-SD) level of 7-ethyl-Gua measured in leukocyte DNA from
      smokers was 49.6 +/- 43.3 (range 14.6-181) fmol/MUmol Gua, while that from
      nonsmokers was 41.3 +/- 34.9 (range 9.64-157) fmol/MUmol Gua. Although a
      significant difference between smokers and nonsmokers was not observed, the
      method described here is unique in the use of high resolution mass spectrometry
      and establishes for the first time the presence of 7-ethyl-Gua in human leukocyte
      DNA.

PMID- 21859141
TI  - Cooperativity in long alpha- and 3(10)-helical polyalanines: both electrostatic
      and van der Waals interactions are essential.
AB  - We have employed the generalized energy-based fragmentation (GEBF) approach to
      investigate the structures, energies, and enthalpies of alpha-helices, 3(10)
      helices, and beta-strands for capped polyalanines, acetyl(ala)(N)NH(2), with N
      values from 8 to 40 at several theoretical levels. The M06-2X functional is
      demonstrated to be much more accurate than the B3LYP functional for peptides
      under study. On the basis of the GEBF-M06-2X results, we find that alpha-helices
      are more stable than the corresponding 3(10)-helices for all peptides with N >=
      10. The cooperative interaction in both helices have not reached their asymptotic
      limits even for N = 40. By comparing the performance of the M06-2X, B3LYP, and
      the van der Waals corrected B3LYP, we show that both electrostatic and van der
      Waals interactions are essential for describing the cooperative interaction in
      long helices. In addition, the greater cooperativity of alpha-helices over 3(10)
      helices in long helices is found to originate mainly from the much stronger van
      der Waals interaction in alpha-helices.

PMID- 21859142
TI  - Strontium and cesium release mechanisms during unsaturated flow through waste
      weathered Hanford sediments.
AB  - Leaching behavior of Sr and Cs in the vadose zone of Hanford site (Washington)
      was studied with laboratory-weathered sediments mimicking realistic conditions
      beneath the leaking radioactive waste storage tanks. Unsaturated column leaching
      experiments were conducted using background Hanford pore water focused on first
      200 pore volumes. The weathered sediments were prepared by 6 months reaction with
      a synthetic Hanford tank waste leachate containing Sr and Cs (10(-5) and 10(-3)
      molal representative of LO- and HI-sediment, respectively) as surrogates for
      (90)Sr and (137)Cs. The mineral composition of the weathered sediments showed
      that zeolite (chabazite-type) and feldspathoid (sodalite-type) were the major
      byproducts but different contents depending on the weathering conditions.
      Reactive transport modeling indicated that Cs leaching was controlled by ion
      exchange, while Sr release was affected primarily by dissolution of the secondary
      minerals. The later release of K, Al, and Si from the HI-column indicated the
      additional dissolution of a more crystalline mineral (cancrinite-type). A two
      site ion-exchange model successfully simulated the Cs release from the LO-column.
      However, a three-site ion-exchange model was needed for the HI-column. The study
      implied that the weathering conditions greatly impact the speciation of the
      secondary minerals and leaching behavior of sequestrated Sr and Cs.

PMID- 21859143
TI  - Photo-cross-linking-assisted thermal stability of DNA origami structures and its
      application for higher-temperature self-assembly.
AB  - Heat tolerance of DNA origami structures has been improved about 30  degrees C by
      photo-cross-linking of 8-methoxypsoralen. To demonstrate one of its applications,
      the cross-linked origami were used for higher-temperature self-assembly, which
      markedly increased the yield of the assembled product when compared to the self
      assembly of non-cross-linked origami at lower-temperature. By contrast, at higher
      temperature annealing, native non-cross-linked tiles did not self-assemble to
      yield the desired product; however, they formed a nonspecific broken structure.

PMID- 21859144
TI  - Structure dependent energy transport: relaxation-assisted 2DIR measurements and
      theoretical studies.
AB  - Vibrational energy relaxation and transport in a molecule that is far from
      thermal equilibrium can affect its chemical reactivity. Understanding the energy
      transport dynamics in such molecules is also important for measuring molecular
      structural constraints via relaxation-assisted two-dimensional infrared (RA 2DIR)
      spectroscopy. In this paper we investigated vibrational relaxation and energy
      transport in the ortho, meta, and para isomers of acetylbenzonitrile (AcPhCN)
      originated from excitation of the CN stretching mode. The amplitude of the cross
      peak among the CN and CO stretching modes served as an indicator for the energy
      transport from the CN group toward the CO group. A surprisingly large difference
      is observed in both the lifetimes of the CN mode and in the energy transport
      rates for the three isomers. The anharmonic DFT calculations and energy transport
      modeling performed to understand the origin of the differences and to identify
      the main cross-peak contributors in these isomers described well the majority of
      the experimental results including mode excited-state lifetimes and the energy
      transport dynamics. The strong dependence of the energy transport on molecular
      structure found in this work could be useful for recognizing different isomers of
      various compounds via RA 2DIR spectroscopy.

PMID- 21859145
TI  - Ligand redox activity and mixed valency in first-row transition-metal complexes
      containing tetrachlorocatecholate and radical tetrachlorosemiquinonate ligands.
AB  - Ligand noninnocence occurs for complexes composed of redox-active ligands and
      metals, with frontier orbitals of similar energy. Usually methods of analysis can
      be used to define the charge distribution, and cases where the metal oxidation
      state and ligand charge are unclear are unusual. Ligands derived from o
      benzoquinones can bond with metals as radical semiquinonates (SQ(*-)) or as
      catecholates (Cat(2-)). Spectroscopic, magnetic, and structural properties can be
      used to assess the metal and ligand charges. With the redox activity at both the
      metal and ligands, reversible multicomponent redox series can be observed using
      electrochemical methods. Steps in the series may occur at either the ligand or
      metal, and ligand substituent effects can be used to tune the range of ligand
      based redox steps. Complexes that appear as intermediates in a ligand-based redox
      series may contain both SQ and Cat ligands "bridged" by the metal as mixed
      valence complexes. Properties reflect the strength of metal-mediated interligand
      electronic coupling in the same way that ligand-bridged bimetallics conform to
      the Robin and Day classification scheme. In this review, we will focus
      specifically on complexes of first-row transition-metal ions coordinated with
      three ligands derived from tetrachloro-1,2-benzoquinone (Cl(4)BQ). The redox
      activity of this ligand overlaps with the potentials of common metal oxidation
      states, providing examples of metal- and ligand-based redox activity, in some
      cases, within a single redox series. The strength of the interligand electronic
      coupling is important in defining the separation between ligand-based couples of
      a redox series. The complex of ferric iron will be described as an example where
      coupling is weak, and the steps associated with the
      Fe(III)(Cl(4)SQ)(3)/[Fe(III)(Cl(4)Cat)(3)](3-) redox series are observed over a
      narrow range in electrochemical potential.

PMID- 21859146
TI  - Identification of a conserved glycan signature for microvesicles.
AB  - Microvesicles (exosomes) are important mediators of intercellular communication,
      playing a role in immune regulation, cancer progression, and the spread of
      infectious agents. The biological functions of these small vesicles are dependent
      on their composition, which is regulated by mechanisms that are not well
      understood. Although numerous proteomic studies of these particles exist, little
      is known about their glycosylation. Carbohydrates are involved in protein
      trafficking and cellular recognition. Glycomic analysis may thus provide valuable
      insights into microvesicle biology. In this study, we analyzed glycosylation
      patterns of microvesicles derived from a variety of biological sources using
      lectin microarray technology. Comparison of the microvesicle glycomes with their
      parent cell membranes revealed both enrichment and depletion of specific glycan
      epitopes in these particles. These include enrichment in high mannose,
      polylactosamine, alpha-2,6 sialic acid, and complex N-linked glycans and
      exclusion of terminal blood group A and B antigens. The polylactosamine signature
      derives from distinct glycoprotein cohorts in microvesicles of different origins.
      Taken together, our data point to the emergence of microvesicles from a specific
      membrane microdomain, implying a role for glycosylation in microvesicle protein
      sorting.

PMID- 21859147
TI  - Chain-branching control of the atomic structure of alkanethiol-based gold-sulfur
      interfaces.
AB  - Density functional theory structure calculations at 0 K and simulations at 300 K
      of observed high-resolution in situ scanning tunneling microscopy (STM) images
      reveal three different atomic-interface structures for the self-assembled
      monolayers (SAMs) of three isomeric butanethiols on Au(111): direct binding to
      the Au(111) surface without pitting, binding to adatoms above a regular surface
      with extensive pitting, and binding to adatoms with local surface vacancies and
      some pitting. Thermal motions are shown to produce some observed STM features,
      with a very tight energy balance controlling the observed structures. Variation
      of the degree of substitution on the alpha carbon is found to significantly
      change the relative energies for interaction of the different types of adatom
      structures with the surface, while the nature of the surface cell, controlled
      primarily by inter-adsorbate steric interactions, controls substrate
      reorganization energies and adsorbate distortion energies. Most significantly, by
      manipulating these features, chemical control of the adsorbate can produce stable
      interfaces with surface pitting eliminated, providing new perspectives for
      technological applications of SAMs.

PMID- 21859149
TI  - Connecting.

PMID- 21859148
TI  - Dynamics of intramolecular electron transfer in dinitrodibenzodioxin radical
      anions.
AB  - The activation energy for intramolecular electron transfer in radical anions of
      2,7-dinitrodibenzodioxin and 2,8-dinitrodibenzodioxin, obtained by simulation of
      their temperature-dependent EPR spectra, are well predicted by the values
      calculated by the two-state Marcus-Hush model from the optical charge-transfer
      bands using quartic-adjusted energy surfaces. The electronic coupling is higher
      in the 2,8-dinitrodibenzodioxin (H(ab) = 485 cm(-1)) than in the 2,7
      dinitrodibenzodioxin radical anion (H(ab) = 250 cm(-1)), but for each solvent the
      reorganization energy, taken as the maximum of the optical band, is only slightly
      higher in the latter. These values are consistent with the fact that the reaction
      is faster in the 2,8-dinitrodibenzodioxin radical anion isomer, as determined by
      EPR spectroscopy. The pre-exponential factors obtained combining the EPR-derived
      rate constants and the activation energies calculated from the optical bands fit
      well the theoretical (modified) nonadiabatic values in the less viscous solvents.
      However, for the more viscous solvents, the trend of the pre-exponential values
      with solvent can only be explained if dynamical solvent effects increasingly
      influence their value. The influence of solvent dynamics in the 2,8
      dinitrodibenzodioxin radical anion starts in the less viscous solvents DMF and
      DMSO, but in the 2,7-dinitrodibenzodioxin isomer this is only fully evident for
      the more viscous PhCN and HMPA. The influence of solvent dynamics is higher in
      the radical with the lowest activation barrier.

PMID- 21859151
TI  - A conversation with Alan Alda: communicating science. Interview by Paul S Weiss.

PMID- 21859152
TI  - Identification of PRDX4 and P4HA2 as metastasis-associated proteins in oral
      cavity squamous cell carcinoma by comparative tissue proteomics of microdissected
      specimens using iTRAQ technology.
AB  - Cervical lymph node metastasis represents the major prognosticator for oral
      cavity squamous cell carcinoma (OSCC). Here, we used an iTRAQ-based quantitative
      proteomic approach to identify proteins that are differentially expressed between
      microdissected primary and metastatic OSCC tumors. The selected candidates were
      examined in tissue sections via immunohistochemistry, and their roles in OSCC
      cell function investigated using RNA interference. Seventy-four differentially
      expressed proteins in nodal metastases, including PRDX4 and P4HA2, were
      identified. Immunohistochemical analysis revealed significantly higher levels of
      PRDX4 and P4HA2 in tumor cells than adjacent non-tumor epithelia (P < 0.0001 and
      P < 0.0001, respectively), and even higher expression in the 31 metastatic tumors
      of lymph nodes, compared to the corresponding primary tumors (P = 0.060 and P =
      0.002, respectively). Overexpression of PRDX4 and P4HA2 was significantly
      associated with positive pN status (P = 0.048 and P = 0.021, respectively). PRDX4
      overexpression was a significant prognostic factor for disease-specific survival
      in both univariate and multivariate analyses (P = 0.034 and P = 0.032,
      respectively). Additionally, cell migration and invasiveness were attenuated in
      OEC-M1 cells upon in vitro knockdown of PRDX4 and P4HA2 with specific interfering
      RNA. Novel metastasis-related prognostic markers for OSCC could be identified by
      our approach.

PMID- 21859153
TI  - Dual signal-responsive liposomes for temperature-controlled cytoplasmic delivery.
AB  - For production of a new type of functional liposome whose destabilization can be
      triggered by a combination of a temperature signal and acidic pH signal, we
      prepared liposomes modified with hyperbranched poly(glycidol) derivatives having
      N-isopropylamide and carboxyl groups. HeLa cells incubated with the dual signal
      responsive liposomes encapsulating a water-soluble fluorescent dye pyranine at 28
      degrees C displayed punctate fluorescence of pyranine, indicating that the
      liposomes were trapped in endosome. However, after heating at 45  degrees C for
      15 min, the same cells exhibited diffuse fluorescence of pyranine, indicating
      that destabilization of the liposomes in endosome with an acidic environment in
      combination with the brief heating caused efficient transfer of the contents into
      cytosol. The dual signal-responsive liposomes might have usefulness for site
      specific delivery of membrane-impermeable molecules, which exhibit bioactivities
      in the intracellular spaces, such as siRNA and proteins.

PMID- 21859154
TI  - Interaction of microbial beta-glucuronidase with vegetable pectins.
AB  - The purpose of this study was to investigate the in vitro effects of vegetable
      carbohydrates on the activity of microbial beta-glucuronidase (betaG) and the
      adsorption of the enzyme on carbohydrates. This study used pectin-protein
      complexes (PPCs) with molecular weights of 300 kDa isolated under conditions
      simulating a gastric environment from cabbage (HCl-PPCC and HCl+pepsin-PPCCP) and
      sweet pepper (PPCP and PPCPP). As a sample for comparison, microcrystalline
      cellulose was used. The activity of betaG from Escherichia coli was determined
      spectrophotometrically by the formation of the colored product from the breakdown
      of phenolphthalein-beta-D-glucuronide. Adsorption of betaG on biopolymers was
      studied by the retention of the enzyme on the membrane of a concentrator with a
      pore diameter of 300 kDa and by native PAGE. PPCCP and PPCC were established to
      increase the activity of betaG by 50 and 100%, respectively. Cellulose had a weak
      effect, whereas pepper PPC had no effect. All studied carbohydrates adsorb on
      betaG. The maximum betaG adsorption (15%) was observed with PPCC, whereas PPCCP
      absorbed 5% of the enzyme. Pepper PPCs and cellulose adsorbed up to 10% of the
      enzyme. There was a positive correlation between the increase of betaG activity
      in the presence of carbohydrates and enzyme adsorption on the polymers (r=0.80;
      P<0.01). The activity of the enzyme in the gel after electrophoresis of the
      PPCC+betaG mixture was inversely proportional to the concentration of PPCC in the
      mixture. A model explaining the effects of cabbage PPCs on the excretion of
      estrogens is proposed.

PMID- 21859155
TI  - Layer-by-layer fabrication of chemical-bonded graphene coating for solid-phase
      microextraction.
AB  - A new fabrication strategy of the graphene-coated solid-phase microextraction
      (SPME) fiber is developed. Graphite oxide was first used as starting coating
      material that covalently bonded to the fused-silica substrate using 3
      aminopropyltriethoxysilane (APTES) as cross-linking agent and subsequently
      deoxidized by hydrazine to give the graphene coating in situ. The chemical
      bonding between graphene and the silica fiber improve its chemical stability, and
      the obtained fiber was stable enough for more than 150 replicate extraction
      cycles. The graphene coating was wrinkled and folded, like the morphology of the
      rough tree bark. Its performance is tested by headspace (HS) SPME of polycyclic
      aromatic hydrocarbons (PAHs) followed by GC/MS analysis. The results showed that
      the graphene-coated fiber exhibited higher enrichment factors (EFs) from 2-fold
      for naphthalene to 17-fold for B(b)FL as compared to the commercial
      polydimethylsioxane (PDMS) fiber, and the EFs increased with the number of
      condensed rings of PAHs. The strong adsorption affinity was believed to be mostly
      due to the dominant role of pi-pi stacking interaction and hydrophobic effect,
      according to the results of selectivity study for a variety of organic compounds
      including PAHs, the aromatic compounds with different substituent groups, and
      some aliphatic hydrocarbons. For PAHs analysis, the graphene-coated fiber showed
      good precision (<11%), low detection limits (1.52-2.72 ng/L), and wide linearity
      (5-500 ng/L) under the optimized conditions. The repeatability of fiber-to-fiber
      was 4.0-10.8%. The method was applied to simultaneous analysis of eight PAHs with
      satisfactory recoveries, which were 84-102% for water samples and 72-95% for soil
      samples, respectively.

PMID- 21859156
TI  - Wet-spinning of amyloid protein nanofibers into multifunctional high-performance
      biofibers.
AB  - Amyloid nanofibers derived from hen egg white lysozyme were processed into
      macroscopic fibers in a wet-spinning process based on interfacial polyion
      complexation using a polyanionic polysaccharide as cross-linker. As a result of
      their amyloid nanostructure, the hierarchically self-assembled protein fibers
      have a stiffness of up to 14 GPa and a tensile strength of up to 326 MPa. Fine
      tuning of the polyelectrolytic interactions via pH allows to trigger the release
      of small molecules, as demonstrated with riboflavin-5'-phophate. The amyloid
      fibrils, highly oriented within the gellan gum matrix, were mineralized with
      calcium phosphate, mimicking the fibrolamellar structure of bone. The formed
      mineral crystals are highly oriented along the nanofibers, thus resulting in a 9
      fold increase in fiber stiffness.

PMID- 21859157
TI  - Structure-guided engineering of a Pacific Blue fluorophore ligase for specific
      protein imaging in living cells.
AB  - Mutation of a gatekeeper residue, tryptophan 37, in E. coli lipoic acid ligase
      (LplA), expands substrate specificity such that unnatural probes much larger than
      lipoic acid can be recognized. This approach, however, has not been successful
      for anionic substrates. An example is the blue fluorophore Pacific Blue, which is
      isosteric to 7-hydroxycoumarin and yet not recognized by the latter's ligase
      ((W37V)LplA) or any tryptophan 37 point mutant. Here we report the results of a
      structure-guided, two-residue screening matrix to discover an LplA double mutant,
      (E20G/W37T)LplA, that ligates Pacific Blue as efficiently as (W37V)LplA ligates 7
      hydroxycoumarin. The utility of this Pacific Blue ligase for specific labeling of
      recombinant proteins inside living cells, on the cell surface, and inside acidic
      endosomes is demonstrated.

PMID- 21859158
TI  - Site-selective imination of an anthracenone sensor: selective fluorescence
      detection of barium(II).
AB  - Site-selective imination of anthraquinone-based macrocyclic crown ethers using
      titanium tetrachloride as the catalyst yields imines where only the external
      carbonyl group of the anthraquinone forms Schiff-bases. The following aromatic
      amines yield monomeric compounds (aniline, 4-nitroaniline, 4-pyrrolaniline, and
      1,3-phenylenediamine). Reaction of 2 equiv of the macrocyclic anthraquinone host
      with 1,2- and 1,4-phenylenediamine yields dimeric imine compounds. The 1,2
      diimino host acts as a luminescence sensor, exhibiting enhanced selectivity for
      Ba(II) ion. Spectroscopic data indicate that two barium ions coordinate to the
      sensor. Due to E/Z isomerization of the imine, the monomeric complexes are
      nonluminescent. Restricted rotation about the 1,2 oriented C?N groups or other
      noncovalent/coordinate-covalent interactions acting between neighboring crown
      ether rings may inhibit E/Z isomerization in this example, which is different
      from current examples that employ coordination of a metal cation with a chelating
      imine nitrogen atom to suppress E/Z isomerization and activate luminescence. The
      1,4-diimino adduct, where the crown rings remain widely separated, remains
      nonluminescent.

PMID- 21859159
TI  - Silica-coated gold nanostars for combined surface-enhanced Raman scattering
      (SERS) detection and singlet-oxygen generation: a potential nanoplatform for
      theranostics.
AB  - This paper reports the synthesis and characterization of surface-enhanced Raman
      scattering (SERS) label-tagged gold nanostars, coated with a silica shell
      containing methylene blue photosensitizing drug for singlet-oxygen generation. To
      our knowledge, this is the first report of nanocomposites possessing a combined
      capability for SERS detection and singlet-oxygen generation for photodynamic
      therapy. The gold nanostars were tuned for maximal absorption in the near
      infrared (NIR) spectral region and tagged with a NIR dye for surface-enhanced
      resonance Raman scattering (SERRS). Silica coating was used to encapsulate the
      photosensitizer methylene blue in a shell around the nanoparticles. Upon 785 nm
      excitation, SERS from the Raman dye is observed, while excitation at 633 nm shows
      fluorescence from methylene blue. Methylene-blue-encapsulated nanoparticles show
      a significant increase in singlet-oxygen generation as compared to nanoparticles
      synthesized without methylene blue. This increased singlet-oxygen generation
      shows a cytotoxic effect on BT549 breast cancer cells upon laser irradiation. The
      combination of SERS detection (diagnostic) and singlet-oxygen generation
      (therapeutic) into a single platform provides a potential theranostic agent.

PMID- 21859160
TI  - Enhanced nucleation rate of polylactide in composites assisted by surface acid
      oxidized carbon nanotubes of different aspect ratios.
AB  - Biodegradable polylactide (PLA) composites added with acid oxidized multiwalled
      carbon nanotubes (A-MWCNTs) of two different aspect ratios (length to diameter)
      were prepared by coagulation. The aspect ratios and surface structures of A
      MWCNTs were characterized by TGA, Raman, and SEM measurements. The percolation
      thresholds for gelation in the PLA composites with A-MWCNTs of large and small
      aspect ratios are 2.5 and 4.0 wt %, respectively, which were determined by a
      rheological method, and in turn, the rheological result confirms the aspect ratio
      differences for the added two types of A-MWCNTs in the composites. Isothermal
      crystallization kinetics of neat PLA and its composites were further investigated
      by using polarized optical microscope (POM) and differential scanning calorimetry
      (DSC) to clarify the effects of A-MWCNTs of different aspect ratios and
      concentrations. The different aspect ratio A-MWCNTs with the same carboxyl group
      mass percent show substantial effects on PLA crystallization kinetics. Those with
      smaller aspect ratios enhance nucleation rate for PLA spherulites much more than
      those with larger aspect ratios. This phenomenon can be attributed to fewer
      sidewall carboxyl groups on the surfaces of A-MWCNTs with smaller aspect ratios,
      which provides more nucleation sites for PLA crystallization than those with
      larger aspect ratios at the same concentration, resulting in faster PLA
      nucleation rates for the former one.

PMID- 21859161
TI  - Rapid detection of microRNA by a silver nanocluster DNA probe.
AB  - MicroRNAs (miRNAs) are regulatory small RNAs that have important roles in
      numerous developmental, metabolic, and disease processes of plants and animals.
      The individual levels of miRNAs can be useful biomarkers for cellular events or
      disease diagnosis. Thus, innovative new tools for rapid, specific, and sensitive
      detection of miRNAs are an important field of research. Using the fluorescence
      properties of DNA-nanosilver clusters (DNA/AgNC), we have designed a DNA/AgNC
      probe that can detect the presence of target miRNA. Here, we show that the red
      fluorescence of the DNA/AgNC probe is diminished upon the presence of target
      miRNA without pre- or postmodification, addition of extra enhancer molecules, and
      labeling. The DNA/AgNC probe emission was lowest when the complementary miRNA
      target was present and was significantly higher for four other control miRNA
      sequences. Also, when adding whole plant endogenous RNA to the DNA/AgNC probe,
      the emission was significantly higher for the mutant where miRNA was deficient.
      On the basis of these findings, we suggest that these DNA/AgNC probes could be
      developed into a new, simple, inexpensive, and instant technique for miRNAs
      detection.

PMID- 21859162
TI  - Viscosity of aqueous solutions and local microscopic structure.
AB  - The effect of solutes on the structure of water has been debated intensively over
      the past years. Typical scenarios label different ions as water structure
      "makers" or "breakers": this is a quite elusive definition, which has been first
      introduced in the description of the effect of solutes on the viscosity of water
      and, although criticized, is still used in the current literature. Here, using a
      combination of neutron diffraction and computer modeling, we present a possible
      relation between the viscosity B coefficient and a local structural property of
      the solution. In particular, B appears in the Jones-Dole relation and its sign is
      traditionally used to characterize a solute as "structure maker" or "breaker". We
      find that B is linearly correlated to the difference between the average solute
      water distance and the water-water distance in the pure liquid, in the case of
      monovalent electrolyte solutions.

PMID- 21859163
TI  - The neural circuitry of conversion disorder and its recovery.
AB  - Little is understood about neural networks associated with conversion disorders.
      This case study reports the first investigation of the neural circuitry
      associated with the recovery of chronic conversion disorder. A patient with a
      four year history of hysterical mutism was assessed with functional MRI (fMRI)
      during a vocalization task, and then provided psychotherapy that attempted to
      reduce motivational factors that maintained mutism. The patient resumed full
      speech, and was readministered the fMRI vocalization task. Vocalization during
      mutism and following recovery of speech resulted in increases in speech-related
      networks, including the inferior frontal gyrus (IFG), middle frontal, and
      supplementary motor area of the frontal cortex, temporal and parietal cortices,
      and also in the primary and sensory motor regions. Following speech recovery but
      not during mutism, the IFG was correlated positively with the anterior cingulate
      cortex and negatively with the amygdala. This pattern suggests that during the
      conversion disorder there was impaired connectivity between speech networks and
      networks that regulate anxiety.

PMID- 21859164
TI  - Negative urgency: a personality predictor of externalizing behavior characterized
      by neuroticism, low conscientiousness, and disagreeableness.
AB  - Negative urgency, the tendency to act rashly when distressed, is characterized by
      high Neuroticism, low Conscientiousness, and low Agreeableness. Because of this
      set of characteristics, the authors hypothesized that (1) negative urgency (NU)
      is a particularly important predictor of externalizing dysfunction; (2) traits
      that reflect primarily high Neuroticism predict internalizing dysfunction; and
      (3) traits that reflect primarily low Conscientiousness predict those types of
      externalizing dysfunction that include intense affect less strongly than does NU.
      In three studies, the authors showed that negative urgency concurrently predicted
      alcohol dependence symptoms in disordered women, drinking problems and smoker
      status in preadolescents, and aggression, risky sex, illegal drug use, drinking
      problems, and conduct disordered behavior in college students. High Neuroticism
      traits predicted internalizing dysfunction but predicted none of these
      externalizing criteria beyond negative urgency. Low Conscientiousness did not add
      to prediction from negative urgency, except in a few cases. The tendency toward
      affect-driven rash action may underlie many externalizing behaviors.

PMID- 21859165
TI  - Quitting-unmotivated and quitting-motivated cigarette smokers exhibit different
      patterns of cue-elicited brain activation when anticipating an opportunity to
      smoke.
AB  - The authors examined the effects of smoking expectancy on cue-reactivity among
      those motivated and those unmotivated to quit smoking using functional MRI. Cue
      elicited activation was observed in the rostral prefrontal cortex (PFC) in
      smokers who expected to smoke within seconds, but not in those who expected to
      have to wait hours before having the chance to smoke, regardless of quitting
      motivation. For quitting-unmotivated smokers expecting to smoke, rostral PFC
      activation was strongly positively correlated with the activation of several
      areas previously linked to cue-reactivity, including the medial orbitofrontal
      cortex (OFC) and rostral anterior cingulate cortex (ACC). In contrast, there was
      a nonsignificant negative relationship between activation of the rostral PFC and
      activation of the medial OFC/rostral ACC in quitting-motivated smokers expecting
      to smoke. Results extend previous work examining the effects of smoking
      expectancy and highlight the utility of examining interregional covariation
      during cue exposure. Findings also suggest that investigators may need to pay
      close attention to the motivational contexts associated with their experiments
      when studying cue-reactivity, as these contexts can modulate not only responses
      to drug cues, but perhaps also the functional implications of observed activity.

PMID- 21859166
TI  - Stress reactivity in social anxiety disorder with and without comorbid
      depression.
AB  - Previous research on neuroendocrine responding to a psychological stressor in
      individuals with Social Anxiety Disorder (SAD) has provided inconsistent results.
      A recent meta-analysis concluded that Major Depressive Disorder (MDD), which is
      frequently comorbid with SAD, is associated with blunted stress reactivity. It
      is, thus, possible that comorbidity status contributes to the inconsistent
      findings in the SAD literature. In this study, salivary cortisol responses to a
      psychological stressor were examined in three groups: healthy controls (CTL),
      SAD, and SAD with comorbid MDD (COM). The SAD group differed from the other two
      groups in their cortisol stress reactivity. It is important to note that analyses
      combining participants with SAD with and without comorbid MDD obscured findings
      of cortisol reactivity. In addition, the differences in cortisol reactivity
      cannot be accounted for by participants' affective responses to the stressor. The
      current findings indicate that individuals with SAD exhibit distinct stress
      related cortisol responses depending on their comorbidity statuses.

PMID- 21859167
TI  - Disentangling the adult attention-deficit hyperactivity disorder endophenotype:
      parametric measurement of attention.
AB  - Attention deficit hyperactivity disorder (ADHD) persists frequently into
      adulthood. The decomposition of endophenotypes by means of experimental neuro
      cognitive assessment has the potential to improve diagnostic assessment,
      evaluation of treatment response, and disentanglement of genetic and
      environmental influences. We assessed four parameters of attentional capacity and
      selectivity derived from simple psychophysical tasks (verbal report of briefly
      presented letter displays) and based on a "theory of visual attention." These
      parameters are mathematically independent, quantitative measures, and previous
      studies have shown that they are highly sensitive for subtle attention deficits.
      Potential reductions of attentional capacity, that is, of perceptual processing
      speed and working memory storage capacity, were assessed with a whole report
      paradigm. Furthermore, possible pathologies of attentional selectivity, that is,
      selection of task-relevant information and bias in the spatial distribution of
      attention, were measured with a partial report paradigm. A group of 30
      unmedicated adult ADHD patients and a group of 30 demographically matched healthy
      controls were tested. ADHD patients showed significant reductions of working
      memory storage capacity of a moderate to large effect size. Perceptual processing
      speed, task-based, and spatial selection were unaffected. The results imply a
      working memory deficit as an important source of behavioral impairments. The
      theory of visual attention parameter working memory storage capacity might
      constitute a quantifiable and testable endophenotype of ADHD.

PMID- 21859169
TI  - Predictors of the severity of depressive symptoms among intravenous heroin users
      receiving methadone maintenance treatment in Taiwan: an 18-month follow-up study.
AB  - This 18-month follow-up study examined the predictors of the severity of
      depressive symptoms among intravenous heroin users receiving methadone
      maintenance treatment (MMT) in Taiwan. The severity of depressive symptoms in 368
      intravenous heroin users receiving MMT in southern Taiwan was assessed using the
      Center for Epidemiological Studies Depression scale at baseline and at 3, 6, 9,
      12, 15, and 18 months of treatment. Demographic and substance-using
      characteristics, severity of heroin use, HIV serostatus, criminal record, and
      family function were collected during baseline interviews. Data on methadone
      dosage at each follow-up interview and the duration of retention in the MMT
      program were also collected. A generalized estimating equation was used to
      determine independent predictors of depressive symptoms during the 18-month
      period of MMT. Female gender, lack of fixed employment, severe heroin use,
      concurrent methamphetamine use, low family function at baseline, heroin use
      during the MMT, low methadone dosage, and short duration of participation in MMT
      predicted more severe depressive symptoms during the 18-month MMT. This study
      found that sociodemographic and substance-using characteristics at baseline
      predicted the severity of depressive symptoms among heroin users receiving MMT.
      Methadone dosage and MMT duration were also predictive of depression severity.
      The predictors found in this study can be used to identify heroin users who are
      at risk for depressive symptoms in the MMT program.

PMID- 21859170
TI  - Guidelines for the practice of parenting coordination.

PMID- 21859168
TI  - Hangover sensitivity after controlled alcohol administration as predictor of post
      college drinking.
AB  - Predicting continued problematic levels of drinking after the early 20's could
      help with early identification of persons at risk. This study investigated
      whether hangover insensitivity could predict postcollege drinking and problems
      beyond the variance due to drinking patterns. In a preliminary study, 134 college
      seniors from a laboratory study of hangover (Time 1) were contacted and assessed
      1-4 years (M = 2.3) later (Time 2). Hangover severity was studied after
      controlled alcohol administration to a specific dose while controlling sleep and
      environmental influences. Hangover severity at Time 1 was used to predict Time 2
      drinking volume and problems while controlling for relevant demographics and Time
      1 drinking volume. Hangover insensitivity at Time 1 tended to predict a clinical
      level of alcohol problems with a large statistical effect size. Hangover
      sensitivity also correlated positively with sensitivity to alcohol intoxication.
      Hangover severity did not predict future drinking volume. Hangover insensitivity
      correlates with insensitivity to intoxication and might predict more serious
      alcohol problems in the future, suggesting that a future larger study is
      warranted. Hangover insensitivity could result from physiological factors
      underlying low sensitivity to alcohol or risk for alcoholism.

PMID- 21859171
TI  - Glutamate and the aggression neural circuit in adolescent anabolic steroid
      treated Syrian hamsters (Mesocricetus auratus).
AB  - Adolescent exposure to anabolic androgenic steroids (AAS) alters the development
      and activity of the glutamate neural system in the latero-anterior hypothalamus
      (LAH) in hamsters (Mesocricetus auratus); that is, an important neural component
      of the adolescent AAS-induced aggressive response. In this article, we used
      retrograde tracing to investigate glutamate-specific alterations in the
      connections between the LAH and several other nuclei implicated in adolescent AAS
      induced aggression. Briefly, hamsters were treated with AAS or sesame-oil control
      during adolescence and then microinjected with retrograde tracer into the medial
      amygdala (MeA), lateral septum (LS), or bed nucleus of the stria terminalis
      (BNST). Brains were then processed for vesicular glutamate transporter 2 (VGLUT2)
      and examined for AAS-induced changes in the number VGLUT2 cells containing
      retrograde tracer (VGLUT2/tracer) within the LAH. It is interesting to note that
      while aggressive AAS-treated hamsters injected retrograde tracer into the MeA
      showed a significant reduction in the number of VGLUT2/tracer cells in the LAH,
      aggressive AAS-treated hamsters injected tracer into the BNST showed a
      significant increase in the number of VGLUT2/tracer cells in the LAH when
      compared with controls. Last, AAS hamsters injected with tracer into the LS had a
      comparable number of LAH-VGLUT2/tracer cells to controls. The current results
      indicate that glutamate likely functions as the major aggression output system
      from the LAH and that adolescent AAS treatment significantly alters the neural
      circuitry modulating aggression. Moreover, increases in the number of glutamate
      projections from the LAH to the BNST in AAS hamsters identify the BNST as an area
      particularly important for the regulation of AAS-induced aggression.

PMID- 21859172
TI  - Pseudoneglect and embryonic light stimulation in the avian brain.
AB  - A bias to allocate attention to the left hemispace, similar to the well-known
      pseudoneglect phenomenon shown by humans, has been recently reported in domestic
      chicks and other species of birds. Asymmetrical light exposure of the embryo of
      the domestic chick in a critical period before hatching is known to be
      responsible for a structural asymmetry in the visual ascending projections of the
      thalamofugal pathway and for lateralization of some visual behaviors. Thus the
      animal model provided by the chick makes possible investigation of the prenatal
      factors that may influence asymmetry in spatial attention. Here chicks coming
      from eggs exposed to light (light incubated, Li-chicks) and chicks incubated in
      darkness (dark incubated, Di-chicks) were tested in a task in which they were
      required to explore an area in front of them and to sample grains of food. The
      results showed that Li-chicks attended more to target stimuli located in the left
      hemispace, whereas no asymmetry was shown by Di-chicks. When grains of food were
      presented with small novel pebbles as distractors, both Li- and Di-chicks tended
      to allocate attention toward the left hemispace. When, however, chicks were
      tested after familiarization with pebbles, no bias was shown by either Li- and Di
      chicks. Hence it seems that cerebral lateralization associated with right
      hemispheric involvement in response to novelty, interacts with the modulatory
      effect of asymmetric embryonic light stimulation on preferential allocation of
      spatial attention in the left hemispace (right hemisphere) and right eye (left
      hemisphere) control of visual discrimination during feeding.

PMID- 21859173
TI  - Blockade of NMDA receptors 2A subunit in the dorsal striatum impairs the learning
      of a complex motor skill.
AB  - Accumulating evidence proposes that the striatum, known to control voluntary
      movement, may also play a role in learning and memory. Striatum learning is
      thought to require long-lasting reorganization of striatal circuits and changes
      in the strength of synaptic connections during the memorization of a complex
      motor task. Whether the ionotropic glutamate receptor N-methyl-D-aspartate
      (NMDAR) contributes to the molecular mechanisms of these memory processes is
      still unclear. The aim of the present study was to investigate the role of
      striatal NMDAR and its subunit composition during the learning of the
      accelerating rotarod task in mice. To this end, we injected directly into the
      dorsal striatum of mice, via chronically implanted cannula, the NMDAR channel
      blocker MK-801 as well as the NR2A and NR2B subunit-selective antagonists NVP
      AAM077 and Ro 25-6981, respectively, before rotarod training. There was no effect
      in the motor performances of mice treated with 1.0 MUg/side of MK-801, 0.1
      MUg/side of NVP-AAM077, or 5 and 10 MUg/side of Ro 25-6981. In contrast,
      injections of 2.5 and 5 MUg/side of MK-801 or 0.5 and 1 MUg/side of NVP-AAM077
      impaired motor learning at Day 3 and 8. Interestingly, treatments with MK-801 and
      NVP-AAM077 did not alter the general motor capacities of mice as revealed by the
      stepping, wire suspension, and pole tests. Our study demonstrates that the NMDAR
      of the dorsal striatum contributes to motor learning, especially during the slow
      acquisition phase, and that NR2A subunits play a critical role in this process.

PMID- 21859175
TI  - Contrast of medical and nonmedical use of stimulant drugs, basis for the
      distinction, and risk of addiction: comment on Smith and Farah (2011).
AB  - Smith and Farah (2011) presented a scholarly review of critical areas related to
      their intriguing title "Are Prescription Stimulants 'Smart Pills'?" We contend
      that they accomplished the main goal of the article, to get the facts straight
      about possible cognitive enhancement via the nonmedical use of stimulant drugs by
      individuals without a diagnosis of attention-deficit/hyperactivity disorder
      (ADHD). At the same time, they justified their main conclusions that (a)
      individuals are seeking and engaging in nonmedical use of stimulant drugs with
      the expectations of cognitive enhancement despite uncertainty whether such
      expectations are valid and (b) on some tasks, there are small average benefits of
      nonmedical use, but the overall pattern is not clear (e.g., small beneficial
      effects across most individuals or large beneficial effects only in a few
      individuals, both of which result in small average effects). We offer comments in
      3 areas to amplify key topics mentioned but not emphasized by Smith and Farah:
      (a) characterization of the cognitive effects of medical use of stimulants to
      contrast with the cognitive effects of nonmedical use; (b) justification of
      medical use of stimulants by placement on a normally distributed dimension of
      behavior rather than categorical diagnosis of ADHD, which varies widely across
      countries; and (c) evaluation of the potential risks of nonmedical use to
      individuals and to society (e.g., the likelihood of addiction to stimulant drugs
      in a small minority of the population) rather than just the potential benefits of
      cognitive enhancement.

PMID- 21859176
TI  - Pharmacological cognitive enhancers: comment on Smith and Farah (2011).
AB  - Smith and Farah (2011) provided a thought-provoking and perhaps deliberately
      provocative literature review of the use of stimulants to improve cognitive
      functioning in humans. They addressed the apparently increasing willingness of
      individuals mostly in the United States to use stimulants for this purpose and
      then summarized published literature that explores whether stimulants actually
      improve specific aspects of neurocognitive function. Although calling for more
      research, they tentatively concluded that stimulants indeed may be "smart pills"
      for some people under certain circumstances. This comment emphasizes that they
      never actually defined the desired qualities of a smart pill, seemed to accept
      the unproven axiom that slight improvements in specific tests constitute
      meaningful enhancement of intelligence, and failed to consider the possible costs
      to individuals and to society of promoting the use of this class of medications
      for such a purpose.

PMID- 21859174
TI  - Are prescription stimulants "smart pills"? The epidemiology and cognitive
      neuroscience of prescription stimulant use by normal healthy individuals.
AB  - Use of prescription stimulants by normal healthy individuals to enhance cognition
      is said to be on the rise. Who is using these medications for cognitive
      enhancement, and how prevalent is this practice? Do prescription stimulants in
      fact enhance cognition for normal healthy people? We review the epidemiological
      and cognitive neuroscience literatures in search of answers to these questions.
      Epidemiological issues addressed include the prevalence of nonmedical stimulant
      use, user demographics, methods by which users obtain prescription stimulants,
      and motivations for use. Cognitive neuroscience issues addressed include the
      effects of prescription stimulants on learning and executive function, as well as
      the task and individual variables associated with these effects. Little is known
      about the prevalence of prescription stimulant use for cognitive enhancement
      outside of student populations. Among college students, estimates of use vary
      widely but, taken together, suggest that the practice is commonplace. The
      cognitive effects of stimulants on normal healthy people cannot yet be
      characterized definitively, despite the volume of research that has been carried
      out on these issues. Published evidence suggests that declarative memory can be
      improved by stimulants, with some evidence consistent with enhanced consolidation
      of memories. Effects on the executive functions of working memory and cognitive
      control are less reliable but have been found for at least some individuals on
      some tasks. In closing, we enumerate the many outstanding questions that remain
      to be addressed by future research and also identify obstacles facing this
      research.

PMID- 21859177
TI  - Discussing smart pills versus endorsing smart pills: reply to Swanson, Wigal, and
      Volkow (2011) and Elliott and Elliott (2011).
AB  - We find much of interest, and little to disagree with, in the commentaries on our
      article. We take issue only with the suggestion that our article was provocative
      and submit that the attempt to understand the use of stimulants as smart pills
      does not imply an endorsement of the practice.

PMID- 21859178
TI  - Between-individual variability and interpretation of associations between
      neurophysiological and behavioral measures in aging populations: comment on
      Salthouse (2011).
AB  - Salthouse (2011) argued that (a) variance between individuals on cognitive test
      scores remains constant between 20 and 90 years of age and (b) widely recognized
      problems of deducing functional relationships from patterns of correlations
      between measurements become especially severe for neuropsychological indices,
      especially for gross indices of age-related brain changes (e.g., losses of brain
      volume or increases in white matter lesions). I argue that between-individual
      variability on cognitive tests does increase with age and provides useful
      information on causes of age-related cognitive decline. I suggest that problems
      of inference from correlations are just as difficult for behavioral as for
      neurophysiological indices and that inclusion, in analyses, of even gross
      measures of brain status such as loss of volume and white matter lesions can
      correct misinterpretations that occur when only behavioral data are examined.

PMID- 21859179
TI  - Only time will tell: cross-sectional studies offer no solution to the age-brain
      cognition triangle: comment on Salthouse (2011).
AB  - Salthouse (2011) critically reviewed cross-sectional and longitudinal relations
      among adult age, brain structure, and cognition (ABC) and identified problems in
      interpretation of the extant literature. His review, however, missed several
      important points. First, there is enough disparity among the measures of brain
      structure and cognitive performance to question the uniformity of B and C
      vertices of the ABC triangle. Second, age differences and age changes in brain
      and cognition are often nonlinear. Third, variances and correlations among
      measures of brain and cognition frequently vary with age. Fourth, cross-sectional
      comparisons among competing models of ABC associations cannot disambiguate
      competing hypotheses about the structure and the range of directed and reciprocal
      relations between changes in brain and behavior. We offer the following
      conclusions, based on these observations. First, individual differences among
      younger adults are not useful for understanding the aging of brain and behavior.
      Second, only multivariate longitudinal studies, age-comparative experimental
      interventions, and a combination of the two will deliver us from the predicaments
      of the ABC triangle described by Salthouse. Mediation models of cross-sectional
      data represent age-related differences in target variables but fail to
      approximate time-dependent relations; thus, they do not elucidate the dimensions
      and dynamics of cognitive aging.

PMID- 21859180
TI  - All data collection and analysis methods have limitations: reply to Rabbitt
      (2011) and Raz and Lindenberger (2011).
AB  - The commentaries on my article contain a number of points with which I disagree
      but also several with which I agree. For example, I continue to believe that the
      existence of many cases in which between-person variability does not increase
      with age indicates that greater variance with increased age is not inevitable
      among healthy individuals up to about 80 years of age. I also do not believe that
      problems of causal inferences from correlational information are more severe in
      the cognitive neuroscience of aging than in other research areas; I contend
      instead that neglect of these problems has led to confusion about neurobiological
      underpinnings of cognitive aging. I agree that researchers need to be cautious in
      extrapolating from cross-sectional to longitudinal relations, but I also note
      that even longitudinal data are limited with respect to their ability to support
      causal inferences.

PMID- 21859181
TI  - Genetic essentialism, neuroessentialism, and stigma: commentary on Dar-Nimrod and
      Heine (2011).
AB  - Dar-Nimrod and Heine (2011) presented a masterfully broad review of the
      implications of genetic essentialism for understandings of human diversity. This
      commentary clarifies the reasons that essentialist thinking has problematic
      social consequences and links genetic forms of essentialism to those invoking
      neural essences. The mounting evidence that these forms of essentialist thinking
      contribute to the stigma of mental disorder is reviewed. Genetic and
      neuroessentialisms influence media portrayals of scientific research and distort
      how they are interpreted by laypeople. The common thread of these essentialisms
      is their tendency to deepen social divisions and promote forms of social
      segregation.

PMID- 21859182
TI  - Genetics and human agency: comment on Dar-Nimrod and Heine (2011).
AB  - Dar-Nimrod and Heine (2011) decried genetic essentialism without denying the
      importance of genetics in the genesis of human behavior, and although I agree on
      both counts, a deeper issue remains unaddressed: how should we adjust our
      cognitions about our own behavior in light of genetic influence, or is it perhaps
      not necessary to take genetics into account at all? I suggest that the genetics
      of behavior does have important implications for how we understand ourselves, the
      differences among us, and the ethical implications of our actions, but that the
      usual metric for these considerations, the heritability coefficient, is not the
      correct one. I propose an alternative.

PMID- 21859183
TI  - Some thoughts on essence placeholders, interactionism, and heritability: reply to
      Haslam (2011) and Turkheimer (2011).
AB  - In the target article (Dar-Nimrod & Heine, 2011), we provided a social-cognitive
      framework which identified genetic essentialist biases and their implications. In
      their commentaries, Haslam (2011) and Turkheimer (2011) indicated their general
      agreement with this framework but highlighted some important points for
      consideration. Haslam suggested that neuroessentialism is a comparable kind of
      essentialist bias and identified similarities with the genetic essentialism
      framework. In response, we acknowledge similarities but also identify qualitative
      and quantitative differences between genetic essentialism and other kinds of
      essentialist biases. Turkheimer challenged us to extend our discussion to address
      the question of how should people respond to genetic etiological information,
      critiqued the use of heritability coefficients, and identified a new construct (1
      - rMZ), which may be termed a free-will coefficient. In response, we emphasize
      the need to transform interactionist explanations from being empty platitudes to
      becoming the default conceptual framework; we wholeheartedly accept his critical
      view of heritability coefficient estimates (but acknowledge a more limited
      utility for them); and we are intrigued by his conceptual interest in identifying
      free-will coefficients yet warn against falling into pitfalls similar to those
      that were stumbled into in the past.

PMID- 21859184
TI  - Effects of transference work in the context of therapeutic alliance and quality
      of object relations.
AB  - OBJECTIVE: Transference interpretation is considered as a core active ingredient
      in dynamic psychotherapy. In common clinical theory, it is maintained that more
      mature relationships, as well as a strong therapeutic alliance, may be
      prerequisites for successful transference work. In this study, the interaction
      between quality of object relations, transference interpretation, and alliance is
      estimated. METHOD: One hundred outpatients seeking psychotherapy for depression,
      anxiety, and personality disorders were randomly assigned to 1 year of weekly
      sessions of dynamic psychotherapy with transference interpretation or to the same
      type and duration of treatment, but without the use of transference
      interpretation. Quality of Object Relations (QOR)-lifelong pattern was evaluated
      before treatment (P. Hoglend, 1994). The Working Alliance Inventory (A. O.
      Horvath & L. S. Greenberg, 1989; T. J. Tracey & A. M. Kokotovic, 1989) was rated
      in Session 7. The primary outcome variable was the Psychodynamic Functioning
      Scales (P. Hoglend et al., 2000), measured at pretreatment, posttreatment, and 1
      year after treatment termination. RESULTS: A significant Treatment Group *
      Quality of Object Relations * Alliance interaction was present, indicating that
      alliance had a significantly different impact on effects of transference
      interpretation, depending on the level of QOR. The impact of transference
      interpretation on psychodynamic functioning was more positive within the context
      of a weak therapeutic alliance for patients with low quality of object relations.
      For patients with more mature object relations and high alliance, the authors
      observed a negative effect of transference work. CONCLUSION: The specific effects
      of transference work was influenced by the interaction of object relations and
      alliance, but in the direct opposite direction of what is generally maintained in
      mainstream clinical theory.

PMID- 21859185
TI  - Cognitive-behavioral therapy, behavioral weight loss, and sequential treatment
      for obese patients with binge-eating disorder: a randomized controlled trial.
AB  - OBJECTIVE: Cognitive-behavioral therapy (CBT) is the best established treatment
      for binge-eating disorder (BED) but does not produce weight loss. The efficacy of
      behavioral weight loss (BWL) in obese patients with BED is uncertain. This study
      compared CBT, BWL, and a sequential approach in which CBT is delivered first,
      followed by BWL (CBT + BWL). METHOD: 125 obese patients with BED were randomly
      assigned to 1 of the 3 manualized treatments delivered in groups. Independent
      assessments were performed posttreatment and at 6- and 12-month follow-ups.
      RESULTS: At 12-month follow-up, intent-to-treat binge-eating remission rates were
      51% (CBT), 36% (BWL), and 40% (CBT + BWL), and mean percent BMI losses were -0.9,
      -2.1, and 1.5, respectively. Mixed-models analyses revealed that CBT produced
      significantly greater reductions in binge eating than BWL through 12-month follow
      up and that BWL produced significantly greater percent BMI loss during treatment.
      The overall significant percent BMI loss in CBT + BWL was attributable to the
      significant effects during the BWL component. Binge-eating remission at major
      assessment points was associated significantly with greater percent BMI loss
      cross-sectionally and prospectively (i.e., at subsequent follow-ups).
      CONCLUSIONS: CBT was superior to BWL for producing reductions in binge eating
      through 12-month follow-up, while BWL produced statistically greater, albeit
      modest, weight losses during treatment. Results do not support the utility of the
      sequential approach of providing BWL following CBT. Remission from binge eating
      was associated with significantly greater percent BMI loss. Findings support BWL
      as an alternative treatment option to CBT for BED.

PMID- 21859186
TI  - Imitation, pretend play, and childhood: essential elements in the evolution of
      human culture?
AB  - There is much controversy over what is needed for culture to flourish and what
      has led human culture to be different from "cultural" characteristics of other
      animals. Here I argue that the emergence of childhood as a step in the life cycle
      was critical to the evolution of the human cultural mind. My line of reasoning is
      built around two complementary features of childhood: imitation and play. When
      children imitate adults they routinely copy unnecessary and arbitrary actions.
      They will persistently replicate how an object is used, even when doing so
      interferes with their ability to produce the very outcome those actions are
      intended to bring about. Though seemingly maladaptive, this behavior provides for
      the faithful transmission of cultural ideas across generations. When children
      play together they commonly construct rules and meanings that exist purely
      because the players agree they "exist." Play thus provides the building blocks
      with which children rehearse the kinds of institutional realities that typify
      cultural practices. I argue that these forms of imitation and play represent a
      foundation upon which human culture flourished and that neither are prevalent in
      nonhuman animals. In light of these arguments evidence will be assessed
      suggesting that childhood emerged relatively late in human evolution.

PMID- 21859187
TI  - The effects of general and homophobic victimization on adolescents' psychosocial
      and educational concerns: the importance of intersecting identities and parent
      support.
AB  - Many adolescents experience peer victimization, which often can be homophobic.
      Applying the minority stress model with attention to intersecting social
      identities, this study tested the effects of general and homophobic victimization
      on several educational outcomes through suicidality and school belonging among
      15,923 adolescents in Grades 7 through 12 on account of their sexual orientation
      and race/ethnicity. Parent support also was tested as a moderator of these
      effects. Homophobic victimization had different effects on suicidality across
      groups, indicating the importance of considering individuals' multiple social
      identities. However, homophobic victimization had universal negative effects on
      school belonging for all groups. Nearly all indirect effects of general and
      homophobic victimization on reported grades, truancy, and importance of
      graduating were significant through suicidality and school belonging across
      groups. Parent support was most consistent in moderating the effects of general
      and homophobic victimization on suicidality for heterosexual White and
      racial/ethnic minority youth. In nearly all cases, it did not moderate the
      effects of general or homophobic victimization for lesbian, gay, bisexual,
      transgender, and questioning youth. Furthermore, in most cases, parent support
      did not moderate the effects of general or homophobic victimization on school
      belonging. Findings underscore the need for counseling psychologists to work with
      parents of all youth on ways to provide support to those who experience
      homophobic victimization. Furthermore, they highlight the need for counseling
      psychologists to be involved as social justice advocates in the passage and
      implementation of school policies that address homophobic bullying and other
      forms of bias-based bullying and harassment.

PMID- 21859188
TI  - Longitudinal examination of the psychosocial costs of racism to Whites across the
      college experience.
AB  - This longitudinal investigation adds to the growing body of scholarship on the
      psychosocial costs of racism to Whites, which refer to the consequences of being
      in the dominant position in an unjust, hierarchical system of societal racism. We
      examined how White students' affective costs of racism (i.e., White empathy,
      guilt, and fear) changed across the college experience and how gender, colorblind
      racial ideology, and diversity experiences were associated with those costs.
      Findings indicated that White empathy, guilt, and fear each had a distinct
      trajectory of change across the college experience. Moreover, patterns of change
      for each cost were moderated by colorblind racial attitude scores at college
      entrance. We also found that participation in college diversity experiences
      (e.g., diversity courses) was associated with the costs; moreover, different
      types of diversity experiences were linked to particular costs. These findings
      provide insight into the affective experiences of White students across college
      and thus may be useful to counseling psychologists and educators who design and
      implement programs and policies to enhance diversity education.

PMID- 21859189
TI  - The role of emotions for moral judgments depends on the type of emotion and moral
      scenario.
AB  - Emotions seem to play a critical role in moral judgment. However, the way in
      which emotions exert their influence on moral judgments is still poorly
      understood. This study proposes a novel theoretical approach suggesting that
      emotions influence moral judgments based on their motivational dimension. We
      tested the effects of two types of induced emotions with equal valence but with
      different motivational implications (anger and disgust), and four types of moral
      scenarios (disgust-related, impersonal, personal, and beliefs) on moral
      judgments. We hypothesized and found that approach motivation associated with
      anger would make moral judgments more permissible, while disgust, associated with
      withdrawal motivation, would make them less permissible. Moreover, these effects
      varied as a function of the type of scenario: the induced emotions only affected
      moral judgments concerning impersonal and personal scenarios, while we observed
      no effects for the other scenarios. These findings suggest that emotions can play
      an important role in moral judgment, but that their specific effects depend upon
      the type of emotion induced. Furthermore, induced emotion effects were more
      prevalent for moral decisions in personal and impersonal scenarios, possibly
      because these require the performance of an action rather than making an abstract
      judgment. We conclude that the effects of induced emotions on moral judgments can
      be predicted by taking their motivational dimension into account. This finding
      has important implications for moral psychology, as it points toward a previously
      overlooked mechanism linking emotions to moral judgments.

PMID- 21859191
TI  - Crossmodal transfer of arousal, but not pleasantness, from the musical to the
      visual domain.
AB  - Arousal and valence (pleasantness) are considered primary dimensions of emotion.
      However, the degree to which these dimensions interact in emotional processing
      across sensory modalities is poorly understood. We addressed this issue by
      applying a crossmodal priming paradigm in which auditory primes (Romantic piano
      solo music) varying in arousal and/or pleasantness were sequentially paired with
      visual targets (IAPS pictures). In Experiment 1, the emotion spaces of 120 primes
      and 120 targets were explored separately in addition to the effects of musical
      training and gender. Thirty-two participants rated their felt pleasantness and
      arousal in response to primes and targets on equivalent rating scales as well as
      their familiarity with the stimuli. Musical training was associated with elevated
      familiarity ratings for high-arousing music and a trend for elevated arousal
      ratings, especially in response to unpleasant musical stimuli. Males reported
      higher arousal than females for pleasant visual stimuli. In Experiment 2, 40
      nonmusicians rated their felt arousal and pleasantness in response to 20 visual
      targets after listening to 80 musical primes. Arousal associated with the musical
      primes modulated felt arousal in response to visual targets, yet no such transfer
      of pleasantness was observed between the two modalities. Experiment 3 sought to
      rule out the possibility of any order effect of the subjective ratings, and
      responses of 14 nonmusicians replicated results of Experiment 2. This study
      demonstrates the effectiveness of the crossmodal priming paradigm in basic
      research on musical emotions.

PMID- 21859190
TI  - The importance of mutual positive expressivity in social adjustment:
      understanding the role of peers and gender.
AB  - The relations between young children's mutual (reciprocated) and overall positive
      emotion (PE) with same- and other-gender peers and their social adjustment were
      explored. Children's PE and peers' PE were observed across the preschool year
      during peer interactions (N = 166; 46% girls; M age = 52 months). Results
      revealed that girls and boys had similar frequencies of overall PE and mutual PE
      when interacting with same-gender peers, but girls were marginally higher
      compared with boys in overall and mutual PE when interacting with other-gender
      peers. Girls and boys did not have greater rates of either type of PE after
      controlling for gender segregation during same- or other-gender interactions.
      Using structural equation modeling, children's mutual PE, regardless of their
      gender, positively predicted indicators of positive adjustment (e.g., prosocial
      behavior, cooperation) and negatively predicted indicators of negative adjustment
      (e.g., hyperactivity, disruption, exclusion by peers). Children's overall PE did
      not predict either type of adjustment. Findings support the importance of mutual
      PE for children's development.

PMID- 21859192
TI  - Odyssey's end: lay conceptions of nostalgia reflect its original Homeric meaning.
AB  - Nostalgia fulfills pivotal functions for individuals, but lacks an empirically
      derived and comprehensive definition. We examined lay conceptions of nostalgia
      using a prototype approach. In Study 1, participants generated open-ended
      features of nostalgia, which were coded into categories. In Study 2, participants
      rated the centrality of these categories, which were subsequently classified as
      central (e.g., memories, relationships, happiness) or peripheral (e.g.,
      daydreaming, regret, loneliness). Central (as compared with peripheral) features
      were more often recalled and falsely recognized (Study 3), were classified more
      quickly (Study 4), were judged to reflect more nostalgia in a vignette (Study 5),
      better characterized participants' own nostalgic (vs. ordinary) experiences
      (Study 6), and prompted higher levels of actual nostalgia and its intrapersonal
      benefits when used to trigger a personal memory, regardless of age (Study 7).
      These findings highlight that lay people view nostalgia as a self-relevant and
      social blended emotional and cognitive state, featuring a mixture of happiness
      and loss. The findings also aid understanding of nostalgia's functions and
      identify new methods for future research.

PMID- 21859194
TI  - Positive and negative affect produce opposing task-irrelevant stimulus
      preexposure effects.
AB  - In three experiments, groups were exposed to either positive or negative affect
      video clips, after which they were presented with a series of task-irrelevant
      stimuli. In the subsequent test task, subjects were required to learn an
      association between the previously irrelevant stimulus and a consequence, and
      between a new stimulus and a consequence. Induced positive affect produced a
      latent inhibition effect (poorer evidence of learning with the previously
      irrelevant stimulus than with the novel stimulus). In opposition to this, induced
      negative affect resulted in better evidence of learning with a previously
      irrelevant stimulus than with a novel stimulus. In general, the opposing effects
      also were present in participants scoring high on self-report questionnaires of
      depression (Experiments 2 and 3). These unique findings were predicted and
      accounted for on the basis of two principles: (a) positive affect broadens the
      attentional field and negative affect contracts it; and (b) task-irrelevant
      stimuli are processed in two successive stages, the first encodes stimulus
      properties, and the second encodes stimulus relationships. The opposing
      influences of negative and positive mood on the processing of irrelevant stimuli
      have implications for the role of emotion in general theories of cognition, and
      possibly for resolving some of the inconsistent findings in research with
      schizophrenia patients.

PMID- 21859193
TI  - Ameliorating intrusive memories of distressing experiences using computerized
      reappraisal training.
AB  - The types of appraisals that follow traumatic experiences have been linked to the
      emergence of posttraumatic stress disorder (PTSD). Could changing reappraisals
      following a stressful event reduce the emergence of PTSD symptoms? The present
      proof-of-principle study examined whether a nonexplicit, systematic computerized
      training in reappraisal style following a stressful event (a highly distressing
      film) could reduce intrusive memories of the film, and symptoms associated with
      posttraumatic distress over the subsequent week. Participants were trained to
      adopt a generally positive or negative poststressor appraisal style using a
      series of scripted vignettes after having been exposed to highly distressing film
      clips. The training targeted self-efficacy beliefs and reappraisals of secondary
      emotions (emotions in response to the emotional reactions elicited by the film).
      Successful appraisal induction was verified using novel vignettes and via change
      scores on the post traumatic cognitions inventory. Compared with those trained
      negatively, those trained positively reported in a diary fewer intrusive memories
      of the film during the subsequent week, and lower scores on the Impact of Event
      Scale (a widely used measure of posttraumatic stress symptoms). Results support
      the use of computerized, nonexplicit, reappraisal training after a stressful
      event has occurred and provide a platform for future translational studies with
      clinical populations that have experienced significant real-world stress or
      trauma.

PMID- 21859195
TI  - Anxiety attenuates awareness of emotional faces during rapid serial visual
      presentation.
AB  - Anxiety limits normative perception and impacts the interaction between key
      neurophysiological systems, possibly by decreasing recruitment of goal-oriented
      processes and increasing recruitment of stimulus-driven processes. Previous
      studies examining the impact of anxiety on emotion processing commonly lack a
      sample with levels of anxiety comparable to a clinical population. Many also fail
      to control for co-occurring symptoms like depression. The current study used
      rapid serial visual presentation (RSVP) with two emotional targets, comparing
      healthy controls to a group of individuals with symptom levels comparable to
      anxiety disorder patients. The results showed a modulatory effect of anxiety; the
      high anxiety (HA) group showed an enhanced impairment in detecting the second of
      two emotional targets relative to the low anxiety (LA) control group. Though
      there were no group-specific effects on the attentional blink or repetition
      blindness, there was a significant interaction of group with first and second
      target valence. Notably, HA individuals showed deficits (where LA individuals
      showed benefits) when the same emotion was presented twice. Further, when the
      first target was neutral, second target detection was especially impaired in HA
      individuals. Correlational analyses confirmed perceptual limitations were related
      to anxiety, but not depression, positive affect, or negative affect. The current
      results, along with past findings, suggest that clinical anxiety leads to
      deficits in overall cognitive control, increased difficulty inhibiting attention
      to distractors, and impairments in rapid, intuitive emotion processing.

PMID- 21859196
TI  - The structure of temperament in preschoolers: a two-stage factor analytic
      approach.
AB  - The structure of temperament traits in young children has been the subject of
      extensive debate, with separate models proposing different trait dimensions. This
      research has relied almost exclusively on parent-report measures. The present
      study used an alternative approach, a laboratory observational measure, to
      explore the structure of temperament in preschoolers. A 2-stage factor analytic
      approach, exploratory factor analyses (n = 274) followed by confirmatory factor
      analyses (n = 276), was used. We retrieved an adequately fitting model that
      consisted of 5 dimensions: Sociability, Positive Affect/Interest, Dysphoria,
      Fear/Inhibition, and Constraint versus Impulsivity. This solution overlaps with,
      but is also distinct from, the major models derived from parent-report measures.

PMID- 21859197
TI  - Would introverts be better off if they acted more like extraverts? Exploring
      emotional and cognitive consequences of counterdispositional behavior.
AB  - People enjoy acting extraverted, and this seems to apply equally across the
      dispositional introversion-extraversion dimension (Fleeson, Malanos, & Achille,
      2002). It follows that dispositional introverts might improve their happiness by
      acting more extraverted, yet little research has examined potential costs of this
      strategy. In two studies, we assessed dispositions, randomly assigned
      participants to act introverted or extraverted, and examined costs-both emotional
      (concurrent negative affect) and cognitive (Stroop performance). Results
      replicated and extended past findings suggesting that acting extraverted produces
      hedonic benefits regardless of disposition. Positive affect increased and
      negative affect did not, even for participants acting out of character. In
      contrast, we found evidence that acting counterdispositionally could produce poor
      Stroop performance, but this effect was limited to dispositional extraverts who
      were assigned to act introverted. We suggest that the positive affect produced by
      introverts' extraverted behavior may buffer the potentially depleting effects of
      counterdispositional behavior, and we consider alternative explanations. We
      conclude that dispositional introverts may indeed benefit from acting extraverted
      more often and caution that dispositional extraverts may want to adopt
      introverted behavior strategically, as it could induce cognitive costs or self
      regulatory depletion more generally.

PMID- 21859198
TI  - Greater emotional empathy and prosocial behavior in late life.
AB  - Emotional empathy and prosocial behavior were assessed in older, middle-aged, and
      young adults. Participants watched two films depicting individuals in need, one
      uplifting and the other distressing. Physiological responses were monitored
      during the films, and participants rated their levels of emotional empathy
      following each film. As a measure of prosocial behavior, participants were given
      an additional payment they could contribute to charities supporting the
      individuals in the films. Age-related linear increases were found for both
      emotional empathy (self-reported empathic concern and cardiac and electrodermal
      responding) and prosocial behavior (size of contribution) across both films and
      in self-reported personal distress to the distressing film. Empathic concern and
      cardiac reactivity to both films, along with personal distress to the distressing
      film only, were associated with greater prosocial behavior. Empathic concern
      partially mediated the age-related differences in prosocial behavior. Results are
      discussed in terms of our understanding both of adult development and of the
      nature of these vital aspects of human emotion.

PMID- 21859199
TI  - Can't suppress this feeling: automatic negative evaluations of somatosensory
      stimuli are related to the experience of somatic symptom distress.
AB  - Cognitive theories of medically unexplained ("somatoform") symptoms stress the
      importance of alterations in attention and memory processes. Accordingly,
      specific schemata are hypothesized to (mis-)guide the processing of somatosensory
      stimuli leading to the formation of symptom-like perceptions. The current study
      tested a possible association between altered automatic somatosensory evaluation
      processes and the tendency to experience somatoform symptoms in a nonclinical
      sample. In a first pilot study, a modified version of the affect misattribution
      procedure (AMP) by Payne, Cheng, Govorun, and Stewart (2005) with aversive and
      nonaversive tactile stimuli (nonpainful electric vs. vibration stimulus) was
      successfully tested in 40 college students. In a second study (n = 50), automatic
      evaluations following aversive tactile stimuli were found to be positively
      associated (r = .35) with somatic symptom distress (PHQ). Moreover, negative
      affectivity significantly moderated this association (i.e., people high on
      negative affectivity revealed the strongest associations between somatic symptom
      distress and negative automatic evaluations in the tactile AMP). The findings
      support cognitive theories of somatoform symptom formation. The tactile AMP is
      suggested as a promising paradigm to study automatic evaluations of body
      sensations in people with somatoform disorders and related clinical conditions.

PMID- 21859200
TI  - Facing good and evil: early brain signatures of affective biographical knowledge
      in face recognition.
AB  - Extracting meaning from faces to understand other people's mental states and
      intentions, and to quickly adjust our actions accordingly, is a vital aspect of
      our social interactions. However, not all emotionally relevant attributes of a
      person are directly observable from facial features or expressions. In this study
      event-related brain potentials were used to investigate the effects of affective
      information about a person's biography that cannot be derived from the visual
      appearance of the face. Faces of well-known and initially unfamiliar persons with
      neutral expressions were associated with negative, positive or neutral
      biographical information. For well-known faces, early event-related brain
      potential (ERP) modulations induced by emotional knowledge, their scalp
      topographies and time course strongly resemble the effects frequently reported
      for emotional facial expressions even though here, access to stored semantic
      knowledge is required. These results demonstrate that visually opaque affective
      knowledge is extracted at high speed and modulates sensory processing in the
      visual cortex.

PMID- 21859204
TI  - Happy mouth and sad eyes: scanning emotional facial expressions.
AB  - There is evidence that specific regions of the face such as the eyes are
      particularly relevant for the decoding of emotional expressions, but it has not
      been examined whether scan paths of observers vary for facial expressions with
      different emotional content. In this study, eye-tracking was used to monitor
      scanning behavior of healthy participants while looking at different facial
      expressions. Locations of fixations and their durations were recorded, and a
      dominance ratio (i.e., eyes and mouth relative to the rest of the face) was
      calculated. Across all emotional expressions, initial fixations were most
      frequently directed to either the eyes or the mouth. Especially in sad facial
      expressions, participants more frequently issued the initial fixation to the eyes
      compared with all other expressions. In happy facial expressions, participants
      fixated the mouth region for a longer time across all trials. For fearful and
      neutral facial expressions, the dominance ratio indicated that both the eyes and
      mouth are equally important. However, in sad and angry facial expressions, the
      eyes received more attention than the mouth. These results confirm the relevance
      of the eyes and mouth in emotional decoding, but they also demonstrate that not
      all facial expressions with different emotional content are decoded equally. Our
      data suggest that people look at regions that are most characteristic for each
      emotion.

PMID- 21859205
TI  - Metacognition of emotional face recognition.
AB  - While humans are adept at recognizing emotional states conveyed by facial
      expressions, the current literature suggests that they lack accurate
      metacognitions about their performance in this domain. This finding comes from
      global trait-based questionnaires that assess the extent to which an individual
      perceives him or herself as empathic, as compared to other people. Those who rate
      themselves as empathically accurate are no better than others at recognizing
      emotions. Metacognition of emotion recognition can also be assessed using
      relative measures that evaluate how well a person thinks s/he has understood the
      emotion in a particular facial display as compared to other displays. While this
      is the most common method of metacognitive assessment of people's judgments of
      learning or their feelings of knowing, this kind of metacognition--"relative meta
      accuracy"--has not been studied within the domain of emotion. As well as asking
      for global metacognitive judgments, we asked people to provide relative, trial-by
      trial prospective and retrospective judgments concerning whether they would be
      right or wrong in recognizing the expressions conveyed in particular facial
      displays. Our question was: Do people know when they will be correct in knowing
      what expression is conveyed, and do they know when they do not know? Although we,
      like others, found that global meta-accuracy was unpredictive of performance,
      relative meta-accuracy, given by the correlation between participants' trial-by
      trial metacognitive judgments and performance on each item, were highly accurate
      both on the Mind in the Eyes task (Experiment 1) and on the Ekman Emotional
      Expression Multimorph task (in Experiment 2).

PMID- 21859206
TI  - Moving faces, looking places: validation of the Amsterdam Dynamic Facial
      Expression Set (ADFES).
AB  - We report two studies validating a new standardized set of filmed emotion
      expressions, the Amsterdam Dynamic Facial Expression Set (ADFES). The ADFES is
      distinct from existing datasets in that it includes a face-forward version and
      two different head-turning versions (faces turning toward and away from viewers),
      North-European as well as Mediterranean models (male and female), and nine
      discrete emotions (joy, anger, fear, sadness, surprise, disgust, contempt, pride,
      and embarrassment). Study 1 showed that the ADFES received excellent recognition
      scores. Recognition was affected by social categorization of the model: displays
      of North-European models were better recognized by Dutch participants, suggesting
      an ingroup advantage. Head-turning did not affect recognition accuracy. Study 2
      showed that participants more strongly perceived themselves to be the cause of
      the other's emotion when the model's face turned toward the respondents. The
      ADFES provides new avenues for research on emotion expression and is available
      for researchers upon request.

PMID- 21859207
TI  - Musical emotions: predicting second-by-second subjective feelings of emotion from
      low-level psychoacoustic features and physiological measurements.
AB  - We sustain that the structure of affect elicited by music is largely dependent on
      dynamic temporal patterns in low-level music structural parameters. In support of
      this claim, we have previously provided evidence that spatiotemporal dynamics in
      psychoacoustic features resonate with two psychological dimensions of affect
      underlying judgments of subjective feelings: arousal and valence. In this article
      we extend our previous investigations in two aspects. First, we focus on the
      emotions experienced rather than perceived while listening to music. Second, we
      evaluate the extent to which peripheral feedback in music can account for the
      predicted emotional responses, that is, the role of physiological arousal in
      determining the intensity and valence of musical emotions. Akin to our previous
      findings, we will show that a significant part of the listeners' reported
      emotions can be predicted from a set of six psychoacoustic features--loudness,
      pitch level, pitch contour, tempo, texture, and sharpness. Furthermore, the
      accuracy of those predictions is improved with the inclusion of physiological
      cues--skin conductance and heart rate. The interdisciplinary work presented here
      provides a new methodology to the field of music and emotion research based on
      the combination of computational and experimental work, which aid the analysis of
      the emotional responses to music, while offering a platform for the abstract
      representation of those complex relationships. Future developments may aid
      specific areas, such as, psychology and music therapy, by providing coherent
      descriptions of the emotional effects of specific music stimuli.

PMID- 21859208
TI  - A Tuesday in the life of a flourisher: the role of positive emotional reactivity
      in optimal mental health.
AB  - Flourishing--a state of optimal mental health--has been linked to a host of
      benefits for the individual and society, including fewer workdays lost and the
      lowest incidence of chronic physical conditions. The aim of this paper was to
      investigate whether and how routine activities promote flourishing. The authors
      proposed that flourishers thrive because they capitalize on the processes
      featured in the broaden-and-build theory of positive emotions, specifically by
      experiencing greater positive emotional reactivity to pleasant events and
      building more resources over time. To test these hypotheses, the Day
      Reconstruction Method (DRM) was administered to a prescreened community sample of
      adults (n = 208), and they were recontacted two to three months later. Results
      showed that relative to those who did not flourish or were depressed, people who
      flourish generally responded with bigger "boosts" in positive emotions in
      response to everyday, pleasant events (helping, interacting, playing, learning,
      spiritual activity), and this greater positive emotional reactivity, over time,
      predicted higher levels of two facets of the cognitive resource of mindfulness.
      In turn, these higher levels of mindfulness were positively associated with
      higher levels of flourishing at the end of study, controlling for initial levels
      of flourishing. These results suggest that the promotion of well-being may be
      fueled by small, yet consequential differences in individuals' emotional
      experience of pleasant everyday events. Additionally, these results underscore
      the utility of the broaden-and-build theory in understanding the processes by
      which flourishing is promoted and provide support for a positive potentiation
      perspective.

PMID- 21859209
TI  - Positive mood + action = negative mood + inaction: effects of general action and
      inaction concepts on decisions and performance as a function of affect.
AB  - General action and inaction concepts have been shown to produce broad, goal
      mediated effects on cognitive and motor activity irrespective of the type of
      activity. The current research tested a model in which action and inaction goals
      interact with the valence of incidental moods to guide behavior. Over four
      experiments, participants' moods were manipulated to be positive (happy),
      neutral, or negative (angry or sad), and then general action, inaction, and
      neutral concepts were primed. In Experiment 1, action primes increased
      intellectual performance when participants experienced a positive (happy) or
      neutral mood, whereas inaction primes increased performance when participants
      experienced a negative (angry) mood. Including a control-prime condition,
      Experiments 2 and 3 replicated these results measuring the number of general
      interest articles participants were willing to read and participants' memory for
      pictures of celebrities. Experiment 4 replicated the results comparing happiness
      with sadness and suggested that the effect of the prime's adoption was automatic.
      Overall, the findings supported an interactive model by which action concepts and
      positive affect produce the same increases in active behavior as inaction
      concepts and negative affect.

PMID- 21859210
TI  - Always look on the broad side of life: happiness increases the breadth of sensory
      memory.
AB  - Research has shown that positive affect increases the breadth of information
      processing at several higher stages of information processing, such as
      attentional selection or knowledge activation. In the present study, we examined
      whether these affective influences are already present at the level of
      transiently storing incoming information in sensory memory, before attentional
      selection takes place. After inducing neutral, happy, or sad affect, participants
      performed an iconic memory task which measures visual sensory memory. In all
      conditions, iconic memory performance rapidly decreased with increasing delay
      between stimulus presentation and test, indicating that affect did not influence
      the decay of iconic memory. However, positive affect increased the amount of
      incoming information stored in iconic memory. In particular, our results showed
      that this occurs due to an elimination of the spatial bias typically observed in
      iconic memory. Whereas performance did not differ at positions where observers in
      the neutral and negative conditions showed the highest performance, positive
      affect enhanced performance at all positions where observers in the neutral and
      negative conditions were relatively "blind." These findings demonstrate that
      affect influences the breadth of information processing already at earliest
      processing stages, suggesting that affect may produce an even more fundamental
      shift in information processing than previously believed.

PMID- 21859211
TI  - A little bit louder now: negative affect increases perceived loudness.
AB  - Traditionally, perception was considered to be an encapsulated process that was
      unaffected by top-down processes like affect. Recent work in vision draws this
      framework into question by showing that changes in the affective state of the
      perceiver can impact many different aspects of visual perception. Here, we extend
      the relationship between affect and perception into another perceptual modality:
      audition. Participants were induced into a negative or neutral mood by writing
      about a frightening or neutral experience in their past. They then listened to a
      series of short, neutral tones (320 and 640 ms) and rated the loudness and
      duration of the tones. Participants in a negative mood rated the tones as
      significantly louder, but not longer, than participants in a neutral mood,
      suggesting that the difference between the groups was perceptual rather than just
      a response bias. This research shows for the first time that the role of affect
      in perceptual processes may be more pervasive than previously considered.

PMID- 21859212
TI  - Effects of acculturation on a culturally adapted diabetes intervention for
      Latinas.
AB  - OBJECTIVE: To inform the refinement of a culturally adapted diabetes
      intervention, we evaluated acculturation's association with variables at several
      sequential steps: baseline measures of diet and physical activity, intervention
      engagement, putative mediators (problem solving and social resources), and
      outcomes (fat consumption and physical activity). METHOD: Latina women (N = 280)
      recruited from health organizations were randomly assigned to a culturally
      adapted lifestyle intervention (!Viva Bien!) or usual care. A brief version of
      the Acculturation Rating Scale for Mexican Americans-II (ARSMA-II) acculturation
      scales (Anglo and Latina orientations) was administered at baseline. Assessments
      at baseline, 6 months, and 12 months included social supportive resources for
      diet and exercise, problem solving, saturated fat consumption, and physical
      activity. RESULTS: Latina orientation was negatively related to saturated fat
      intake and physical activity at baseline. Latina orientation also was positively
      related to session attendance during Months 6-12 of the intervention. Independent
      of 6-month intervention effects, Anglo orientation was significantly positively
      related to improvements in problem solving and dietary supportive resources.
      Anglo orientation related negatively to improved physical activity at 6 and 12
      months. There were no Acculturation * Intervention interactions on putative
      mediators or outcomes. CONCLUSION: The cultural adaptation process was successful
      in creating an engaging and effective intervention for Latinas at all levels of
      acculturation. However, independent of intervention effects, acculturation was
      related to putative mediating variables (problem solving and social resources)
      and an outcome variable (physical activity), an indication of acculturation's
      general influence on lifestyle and coping factors.

PMID- 21859213
TI  - Marriage and long-term survival after coronary artery bypass grafting.
AB  - OBJECTIVE: To examine the effects of marital status and marital satisfaction on
      survival after coronary artery bypass grafting (CABG). METHODS: Participants were
      225 people who had CABG between 1987 and 1990. Marital status at the time of
      surgery and marital satisfaction 1 year after surgery were used to predict
      survival 15 years after surgery. RESULTS: Married people were 2.5 times (p <
      .001) more likely to be alive 15 years after CABG than those who were not
      married. This finding was true for men and women, although the result for women
      was marginally significant adjusting for age. Those in high-satisfaction
      marriages were 3.2 times (p < .003) more likely to be alive 15 years after CABG
      compared with those reporting low marital satisfaction. Highly satisfied men were
      2.7 times (p < .03) and highly satisfied women were 3.9 times (p < .15) more
      likely to be alive adjusting for age. Although the result was not significant for
      women, the effect size for marital satisfaction was actually larger for women
      than for men. CONCLUSIONS: Being married, especially being in a highly satisfying
      marriage, offered a significant benefit to long-term survival after CABG. Why
      marital status and marital satisfaction have this effect on survival is surely
      mulitfactorial, most likely a combination of spousal support and survivor
      motivation to adopt a healthy lifestyle, along with the provision of emotional
      support to the survivor, which all could have the effect of modulating the
      physiologic mechanisms responsible for slowing the advancement of CVD.

PMID- 21859214
TI  - Attachment predicts daily catastrophizing and social coping in women with pain.
AB  - OBJECTIVE: To examine how anxious and avoidant adult attachment styles moderate
      within-day associations between pain intensity, pain catastrophizing, and social
      coping. METHOD: Two-hundred and ten women with osteoarthritis and/or fibromyalgia
      from the community completed an initial questionnaire assessing attachment
      dimensions and a 30 day electronic diary. Outcomes were measured with daily
      ratings of pain intensity, catastrophizing, and social coping. RESULTS:
      Attachment anxiety showed a context-specific relation with catastrophizing: days
      of increased pain predicted greater increases in pain catastrophizing for women
      who were anxious compared to nonanxious women. Attachment avoidance scores were
      related to higher mean levels of pain intensity and pain catastrophizing, and
      lower mean levels of social coping, across the diary period. In addition,
      compared to nonavoidant women, avoidant women showed smaller increases in use of
      social coping strategies on days of high catastrophizing. CONCLUSIONS: Dimensions
      of adult attachment, anxiety and avoidance, predict different aspects of daily
      pain and pain coping in women with chronic pain. Findings suggest that a social
      development perspective can inform our understanding of adjustment to chronic
      pain and the creation and use of more effective prevention and treatment
      strategies.

PMID- 21859215
TI  - The role of prepartum motivation in the maintenance of postpartum smoking
      abstinence.
AB  - OBJECTIVE: Motivation plays an important role in a variety of behaviors,
      including smoking cessation, and is integral to theory and treatment of smoking.
      For many women, pregnancy offers a motivational shift that helps them stop
      smoking and maintain abstinence during pregnancy. However, women's motivation to
      maintain smoking abstinence postpartum is not well-understood and may play a role
      in high postpartum relapse rates. The current study utilized multiple measures of
      prepartum motivation to maintain smoking abstinence to predict postpartum smoking
      abstinence. METHODS: As part of a randomized clinical trial on postpartum smoking
      relapse prevention, pregnant women who quit smoking during pregnancy reported
      their motivation to continue smoking abstinence at a prepartum baseline session.
      Biochemically verified continued smoking abstinence was assessed at 8 and 26
      weeks postpartum. RESULTS: Direct relationships among multiple measures of
      motivation were significant, and ranged in strength from weak to moderate. All
      motivation measures individually predicted continuous smoking abstinence, after
      controlling for treatment group, demographics, and prequit tobacco use. When
      tested simultaneously, a global motivation measure and parenthood motives for
      quitting remained significant predictors of abstinence. Backward selection
      modeling procedures resulted in a reduced model of prepartum predictors of
      postpartum abstinence including global motivation, parenthood motives, and stage
      of change. CONCLUSIONS: Global motivation for smoking abstinence and parenthood
      motives for quitting are particularly important motivational constructs for
      pregnant women's continued smoking abstinence.

PMID- 21859216
TI  - Trial-and-error learning improves source memory among young and older adults.
AB  - Trial-and-error learning, relative to errorless learning, has been shown to
      impair memory among older adults, despite evidence from young adults that errors
      may afford memorial benefits through richer encoding. However, previous studies
      on the effects of errorless versus trial-and-error learning in older adults has
      required production of errors based on perceptual cues. We hypothesized that
      producing errors conceptually associated with targets would boost memory for the
      encoding context in which information was studied, especially for older adults
      who do not spontaneously elaborate on targets at encoding. We report two studies
      examining the impact of generating errors during learning on source memory among
      young and older adults, with a process dissociation procedure employed in Study
      1, and source memory assessed directly in Study 2. In both studies, participants
      were shown semantic category cues and generated an exemplar either with or
      without errors. In Study 1, for both age groups trial-and-error learning was
      associated with lower familiarity-based memory and higher recollection-based
      memory relative to errorless learning, and the latter effect was more marked for
      older than younger adults. Similarly, in Study 2, trial-and-error learning was
      associated with better source memory relative to errorless learning, particularly
      for the older adults. We argue that trial-and-error learning can enhance source
      memory and confer memorial benefits when making such errors facilitates semantic
      elaboration, especially for older adults who do not spontaneously engage in
      strategic encoding.

PMID- 21859217
TI  - Children's Depression Inventory: invariance across children and adolescents with
      and without depressive disorders.
AB  - In the study, the authors examined the measurement (configural, factor loadings,
      thresholds, and error variances) and structural (factor variances, covariances,
      and mean scores) invariance of the Children's Depression Inventory (CDI; Kovacs,
      1992) across ratings provided by clinic-referred children and adolescents with (N
      = 383) and without (N = 412) depressive disorders. Multiple-group confirmatory
      factor analysis of the Craighead, Smucker, Craighead, and Ilardi (1998) CDI model
      supported full measurement invariance and invariance for structural variances and
      covariances. Invariance for thresholds was also supported by multiple indicators
      multiple causes (MIMIC) procedures that controlled for the effects of age; sex;
      and the presence or absence of anxiety disorders, attention-deficit/hyperactivity
      disorder, and oppositional defiant/conduct disorders. The MIMIC analyses showed
      that for latent mean scores, the group with depressive disorders had higher
      scores, with at least medium effect sizes, for Self-Deprecation and Biological
      Dysregulation. The theoretical, psychometric, and clinical implications of the
      findings are discussed.

PMID- 21859218
TI  - Assessing planning ability with the Tower of London task: psychometric properties
      of a structurally balanced problem set.
AB  - In clinical and experimental settings, planning ability is typically assessed
      using the Tower of London (ToL) or one of its variants. For enhancing the
      comparability across studies, a common ToL problem set was recently suggested
      comprising a collection of 4- to 7-move problems. Based on previous theoretical
      and empirical analyses of problem space and task structure, development of the
      problem set accounted particularly for the influence of structural problem
      parameters on the detection of individual differences in planning ability. To
      assess its adequacy as a clinical and research instrument, the present study
      evaluated the psychometric properties of the suggested problem set. Results
      showed a clear and nearly perfect linear increase of task difficulty across
      minimum moves. Given a broad range of item difficulty, high- and low-achieving
      subjects could be well discriminated. The test scores' split-half reliability (r
      = .72) and internal consistency (alpha = .69) were satisfactory. Taken together,
      the ToL problem set evaluated here proved to have good psychometric qualities and
      constitutes a conceptually sound basis for diagnostic and research purposes.

PMID- 21859219
TI  - Adolescents with suicidal and nonsuicidal self-harm: clinical characteristics and
      response to therapeutic assessment.
AB  - Self-harm is one of the best predictors of death by suicide, but few studies
      directly compare adolescents with suicidal versus nonsuicidal self-harm. Seventy
      adolescents presenting with self-harm (71% young women, ages 12-18 years) who
      participated in a randomized controlled trial were divided into suicidal and
      nonsuicidal self-harm categories using the Columbia Classification Algorithm of
      Suicide Assessment. Adolescents with suicidal self-harm were more likely than
      those with nonsuicidal self-harm to be young women, 22/23 (96%) versus 34/47
      (72%), odds ratio (OR) = 8.33, 95% confidence interval (CI) [1.03, 50.0]; had a
      later age of onset of self-harm, 15.4 years vs. 13.8 years, mean difference =
      1.6, 95% CI [.8, 2.43]; and used self-poisoning more often, 18/23 (78%) versus
      11/47 (23%), OR = 3.43, 95% CI [2.00, 5.89]. Only those with nonsuicidal self
      harm had an improvement on Children's Global Assessment Scale score following a
      brief therapeutic intervention, mean difference = 8.20, 95% CI [.97, 15.42].
      However, there was no interaction between treatment and suicidality. There are
      important differences between adolescents presenting with suicidal and
      nonsuicidal self-harm. Suicidal self-harm in adolescence may be associated with a
      less favorable response to therapeutic assessment.

PMID- 21859220
TI  - A transportable assessment protocol for prescribing youth psychosocial treatments
      in real-world settings: reducing assessment burden via self-report scales.
AB  - Current evidence-based assessment methods, such as structured interviews and
      lengthy assessment batteries, often require hours to administer, score, and
      interpret and thus are infrequently used in real-world practice. As evidence
      based assessment tools are developed for implementation in real-world youth
      mental health settings, the transportability properties of assessment procedures
      (including administration and interpretation burden) need to be considered and
      improved. In the present study, we thus conducted an initial feasibility study
      using a clinical sample of community-based youths (N = 306) to develop an
      assessment protocol based on 2 child and 2 parent self-report questionnaires
      (thus low on administration burden). Using decision-tree analysis, we identified
      a series of cutoff scores across these scales that may be used to inform
      treatment need related to anxiety, depression, attention-deficit/hyperactivity
      disorder (ADHD), and disruptive behavior problems. This algorithm-based approach
      to interpreting assessment information provided clear and simple guidelines (thus
      low on interpretation burden) that matched the best estimate treatment
      determinations derived by trained assessors, supervisors, and expert consultants
      who integrated information provided by child and parent structured interviews and
      self-report scales. The present study demonstrated the feasibility of developing
      an assessment protocol to inform various treatment allocation decisions in a way
      that imposes little assessment administration and interpretation burden yet
      maintains adequate classification accuracy. These characteristics make the
      proposed protocol promising with regard to its transportability and suitability
      for adoption and implementation in real-world mental health settings.

PMID- 21859221
TI  - Comparative validity of brief to medium-length Big Five and Big Six Personality
      Questionnaires.
AB  - A general consensus on the Big Five model of personality attributes has been
      highly generative for the field of personality psychology. Many important
      psychological and life outcome correlates with Big Five trait dimensions have
      been established. But researchers must choose between multiple Big Five
      inventories when conducting a study and are faced with a variety of options as to
      inventory length. Furthermore, a 6-factor model has been proposed to extend and
      update the Big Five model, in part by adding a dimension of Honesty/Humility or
      Honesty/Propriety. In this study, 3 popular brief to medium-length Big Five
      measures (NEO Five Factor Inventory, Big Five Inventory [BFI], and International
      Personality Item Pool), and 3 six-factor measures (HEXACO Personality Inventory,
      Questionnaire Big Six Scales, and a 6-factor version of the BFI) were placed in
      competition to best predict important student life outcomes. The effect of test
      length was investigated by comparing brief versions of most measures (subsets of
      items) with original versions. Personality questionnaires were administered to
      undergraduate students (N = 227). Participants' college transcripts and student
      conduct records were obtained 6-9 months after data was collected. Six-factor
      inventories demonstrated better predictive ability for life outcomes than did
      some Big Five inventories. Additional behavioral observations made on
      participants, including their Facebook profiles and cell-phone text usage, were
      predicted similarly by Big Five and 6-factor measures. A brief version of the BFI
      performed surprisingly well; across inventory platforms, increasing test length
      had little effect on predictive validity. Comparative validity of the models and
      measures in terms of outcome prediction and parsimony is discussed.

PMID- 21859222
TI  - A novel clinical test of recognition reaction time in healthy adults.
AB  - We evaluated a clinical "go/no-go" reaction time test (recognition RTclin) that
      is portable and does not require a computer, and used it to quantify the effect
      of age on recognition RTclin test scores. Fifty-two healthy adults 19-83 years
      old completed simple and recognition RTclin testing. Simple RTclin was measured
      as the elapsed time from initial release of a suspended vertical shaft by the
      examiner until its arrest by participant pinch grip. Recognition RTclin was
      similar except that a light on the apparatus randomly illuminated in 50% of the
      trials to signal the participant to arrest the device. To help interpret the
      RTclin results, we partitioned them into premovement time (PMT) and movement time
      (MT) using an optoelectronic camera system that is not ordinarily part of the
      RTclin test. Recognition RTclin scores were significantly slower than simple
      RTclin scores, with 71% of the prolongation attributable to PMT. While simple
      RTclin test scores correlated with age, recognition RTclin scores did not. A
      strong negative association between recognition RTclin accuracy and age was
      found. Recognition RTclin is feasible to measure in healthy adults and appears to
      represent a portable, computer-independent measure of cognitive processing speed
      and inhibitory capacity. Potential applications include assessment of brain
      injury, dementing illness, medication side effects, fall risk, and safe driving.

PMID- 21859224
TI  - Malleability in communal goals and beliefs influences attraction to stem careers:
      evidence for a goal congruity perspective.
AB  - The goal congruity perspective posits that 2 distinct social cognitions predict
      attraction to science, technology, engineering, or mathematics (STEM) fields.
      First, individuals may particularly value communal goals (e.g., working with or
      helping others), due to either chronic individual differences or the salience of
      these goals in particular contexts. Second, individuals hold beliefs about the
      activities that facilitate or impede these goals, or goal affordance stereotypes.
      Women's tendency to endorse communal goals more highly than do men, along with
      consensual stereotypes that STEM careers impede communal goals, intersect to
      produce disinterest in STEM careers. We provide evidence for the foundational
      predictions that gender differences emerge primarily on communal rather than
      agentic goals (Studies 1a and 3) and that goal affordance stereotypes reflect
      beliefs that STEM careers are relatively dissociated from communal goals (Studies
      1b and 1c). Most critically, we provide causal evidence that activated communal
      goals decrease interest in STEM fields (Study 2) and that the potential for a
      STEM career to afford communal goals elicits greater positivity (Study 3). These
      studies thus provide a novel demonstration that understanding communal goals and
      goal affordance stereotypes can lend insight into attitudes toward STEM pursuits.

PMID- 21859223
TI  - The effects of acute alcohol intoxication, partner risk level, and general
      intention to have unprotected sex on women's sexual decision making with a new
      partner.
AB  - Women account for a quarter of all new HIV/AIDS cases, with approximately 65%
      having contracted the infection via heterosexual contact. Few experimental
      studies have examined interactions among background, partner, and situational
      characteristics in predicting women's sexual decisions. The Cognitive Mediation
      Model provides a useful theoretical framework for assessing likelihood of
      unprotected sex. Female social drinkers (n = 230) who had answered questions
      related to their general intention to have unprotected sex were randomly assigned
      to an experimental condition based on partner risk level (unknown, low, high) and
      beverage (control, placebo, low dose, high dose). Participants projected
      themselves into a story depicting a sexual situation with a man and answered
      questions about their cognitive appraisals, assertive condom request, and
      likelihood of unprotected sex. Alcohol effects on appraisal of sexual potential
      differed by partner risk condition. In the unknown and low risk conditions,
      placebo and alcohol participants appraised the situation as having greater sexual
      potential than controls whereas in the high risk condition, only those who
      consumed alcohol did so. Sexual potential appraisals in turn predicted impelling
      cognitions about having sex, which in turn predicted assertive condom request and
      unprotected sex intentions. General intention for unprotected sex independently
      predicted cognitive appraisals and outcomes. These findings highlight the need
      for prevention programs that focus on teaching women how to pay attention and
      consider sexual risk cues presented by potential partners, particularly when
      under the influence of alcohol.

PMID- 21859225
TI  - The "CEO" of women's work lives: how Big Five Conscientiousness, Extraversion,
      and Openness predict 50 years of work experiences in a changing sociocultural
      context.
AB  - Few long-term longitudinal studies have examined how dimensions of personality
      are related to work lives, especially in women. We propose a life-course
      framework for studying work over time, from preparatory activities (in the 20s)
      to descending work involvement (after age 60), using 50 years of life data from
      the women in the Mills Longitudinal Study. We hypothesized differential work
      effects for Extraversion (work as pursuit of rewards), Openness (work as self
      actualization), and Conscientiousness (work as duty) and measured these 3 traits
      as predictor variables when the women were still in college. In a prospective
      longitudinal design, we then studied how these traits predicted the women's
      subsequent work lives from young adulthood to age 70 and how these effects
      depended on the changing sociocultural context. Specifically, the young adulthood
      of the Mills women in the mid-1960s was rigidly gender typed and family oriented;
      neither work nor education variables at that time were predicted from earlier
      personality traits. However, as women's roles changed, later work variables
      became related to all 3 traits, as expected from current Big Five theory and
      research. For example, early personality traits predicted the timing of
      involvement in work, the kinds of jobs chosen, and the status and satisfaction
      achieved, as well as continued work participation and financial security in late
      adulthood. Early traits were also linked to specific cultural influences, such as
      the traditional feminine role, the women's movement, and graduate education for
      careers.

PMID- 21859226
TI  - Stability and change of personality across the life course: the impact of age and
      major life events on mean-level and rank-order stability of the Big Five.
AB  - Does personality change across the entire life course, and are those changes due
      to intrinsic maturation or major life experiences? This longitudinal study
      investigated changes in the mean levels and rank order of the Big Five
      personality traits in a heterogeneous sample of 14,718 Germans across all of
      adulthood. Latent change and latent moderated regression models provided 4 main
      findings: First, age had a complex curvilinear influence on mean levels of
      personality. Second, the rank-order stability of Emotional Stability,
      Extraversion, Openness, and Agreeableness all followed an inverted U-shaped
      function, reaching a peak between the ages of 40 and 60 and decreasing afterward,
      whereas Conscientiousness showed a continuously increasing rank-order stability
      across adulthood. Third, personality predicted the occurrence of several
      objective major life events (selection effects) and changed in reaction to
      experiencing these events (socialization effects), suggesting that personality
      can change due to factors other than intrinsic maturation. Fourth, when events
      were clustered according to their valence, as is commonly done, effects of the
      environment on changes in personality were either overlooked or overgeneralized.
      In sum, our analyses show that personality changes throughout the life span, but
      with more pronounced changes in young and old ages, and that this change is
      partly attributable to social demands and experiences.

PMID- 21859227
TI  - Does familiarity breed contempt or liking? Comment on Reis, Maniaci, Caprariello,
      Eastwick, and Finkel (2011).
AB  - Reis, Maniaci, Caprariello, Eastwick, and Finkel (see record 2011-04644-001)
      conducted 2 studies that demonstrate that in certain cases, familiarity can lead
      to liking--in seeming contrast to the results of our earlier article (see record
      2006-23056-008). We believe that Reis et al. (a) utilized paradigms far removed
      from spontaneous, everyday social interactions that were particularly likely to
      demonstrate a positive link between familiarity and liking and (b) failed to
      include and incorporate other sources of data-both academic and real-world
      showing that familiarity breeds contempt. We call for further research exploring
      when and why familiarity is likely to lead to contempt or liking, and we suggest
      several factors that are likely to inform this debate.

PMID- 21859228
TI  - In live interaction, does familiarity promote attraction or contempt? Reply to
      Norton, Frost, and Ariely (2011).
AB  - In this reply, we address and refute each of Norton, Frost, and Ariely's (see
      record 2011-18560-001) specific objections to the conclusion that, ceteris
      paribus, familiarity breeds liking in live interaction. In particular, we
      reiterate the importance of studying live interaction rather than
      decontextualized processes. These rebuttals notwithstanding, we concur with
      Norton et al.'s call for an integrative model that encompasses both Norton,
      Frost, and Ariely's (see record 2006-23056-008) results and ours (see record 2011
      04644-001), and we point readers toward a description of a possible model
      presented in our original article.

PMID- 21859229
TI  - The dark side of testing memory: repeated retrieval can enhance eyewitness
      suggestibility.
AB  - Eyewitnesses typically recount their experiences many times before trial. Such
      repeated retrieval can enhance memory retention of the witnessed event. However,
      recent studies (e.g., Chan, Thomas, & Bulevich, 2009) have found that initial
      retrieval can exacerbate eyewitness suggestibility to later misleading
      information--a finding termed retrieval-enhanced suggestibility (RES). Here we
      examined the influence of multiple retrieval attempts on eyewitness
      suggestibility to subsequent misinformation. In four experiments, we
      systematically varied the number of initial tests taken (between zero and six),
      the delay between initial testing and misinformation exposure (~30 min or 1
      week), and whether initial testing was manipulated between- or within-subjects.
      University undergraduate students were used as participants. Overall, we found
      that eyewitness suggestibility increased as the number of initial tests
      increased, but this RES effect was qualified by the delay and by whether initial
      testing occurred in a within- or between-subjects manner. Specifically, the
      within-subjects RES effect was smaller than the between-subjects RES effect,
      possibly because of the influence of retrieval-induced forgetting/facilitation
      (Chan, 2009) when initial testing was manipulated within subjects. Moreover,
      consistent with the testing effect literature (Roediger & Karpicke, 2006), the
      benefits of repeated testing on later memory were stronger after a 1-week delay
      than after a 30-min delay, thus reducing the negative impact of RES in long-term
      situations. These findings suggest that conditions that are likely to occur in
      criminal investigations can either increase (repeated testing) or reduce (delay)
      the influence of RES, thus further demonstrating the complex relationship between
      eyewitness memory and repeated retrieval.

PMID- 21859230
TI  - Changes in team cognition after a retention interval: the benefits of mixing it
      up.
AB  - This paper examines the retention of team cognition with changes in team
      membership. Hypotheses are developed from shared cognition and interactive team
      cognition theories. We report a study of the effects of Short (3-6 weeks) versus
      Long (10-13 weeks) retention intervals and change (Mixed) versus no change
      (Intact) in team membership during the interval on shared knowledge, team
      process, and team performance. The study context was a three-person Unmanned
      Aerial Vehicle (UAV) simulator. The long retention interval resulted in
      significantly lower team process scores and, except for the Short-Intact
      condition, all teams suffered a drop in performance after the break. However,
      those teams recovered prebreak levels of performance after one UAV mission. The
      counterintuitive result was that team mixing resulted in significant knowledge
      and process gains. An exploratory communication analysis indicated that Mixed
      team communication is longer in duration than Intact team communication, and Long
      interval teams communicated more frequently than Short-interval teams. Unlike the
      Long-interval communication frequency effect, the Mixed team communication
      duration effect lasted throughout the experiment, suggesting greater interaction
      experience for Mixed teams. An exploratory mediation analysis indicated that the
      shared cognition Input-Process-Output framework was a good fit for the Intact
      team data, but not for the Mixed team data. We conclude that there are team
      learning benefits of team mixing and that the interactive team cognition theory
      accounts better for those benefits than shared cognition theory.

PMID- 21859231
TI  - What limits working memory capacity? Evidence for modality-specific sources to
      the simultaneous storage of visual and auditory arrays.
AB  - There is considerable debate on whether working memory (WM) storage is mediated
      by distinct subsystems for auditory and visual stimuli (Baddeley, 1986) or
      whether it is constrained by a single, central capacity-limited system (Cowan,
      2006). Recent studies have addressed this issue by measuring the dual-task cost
      during the concurrent storage of auditory and visual arrays (e.g., Cocchini,
      Logie, Della Sala, MacPherson, & Baddeley, 2002; Fougnie & Marois, 2006; Saults &
      Cowan, 2007). However, studies have yielded widely different dual-task costs,
      which have been taken to support both modality-specific and central capacity
      limit accounts of WM storage. Here, we demonstrate that the controversies
      regarding such costs mostly stem from how these costs are measured. Measures that
      compare combined dual-task capacity with the higher single-task capacity support
      a single, central WM store when there is a large disparity between the single
      task capacities (Experiment 1) but not when the single-task capacities are well
      equated (Experiment 2). In contrast, measures of the dual-task cost that
      normalize for differences in single-task capacity reveal evidence for modality
      specific stores, regardless of single-task performance. Moreover, these
      normalized measures indicate that dual-task cost is much smaller if the tasks do
      not involve maintaining bound feature representations in WM (Experiment 3). Taken
      together, these experiments not only resolve a discrepancy in the field and
      clarify how to assess the dual-task cost but also indicate that WM capacity can
      be constrained both by modality-specific and modality-independent sources of
      information processing.

PMID- 21859233
TI  - Dividing attention lowers children's but increases adults' false memories.
AB  - The present study examined the impact of divided attention on children's and
      adults' neutral and negative true and false memories in a standard Deese/Roediger
      McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52)
      received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of
      each group also received a divided attention task. The results showed that
      divided attention affected children's and adults' false memory levels differently
      but did not alter true memory differently. Our results revealed a developmental
      shift in that divided attention lowered children's false memory rates but
      increased adults' false memory rates, regardless of the nature of the material
      (i.e., neutral or negative). Our study indicates that manipulations that target
      conscious processing (e.g., divided attention) result in marked qualitative and
      quantitative differences between children's and adults' false memories but not
      true memories.

PMID- 21859232
TI  - Familiarity and personal experience as mediators of recall when planning for
      future contingencies.
AB  - In this article, we demonstrate that planning tasks enhance recall when the
      context of planning (a) is self-referential and (b) draws on familiar scenarios
      represented in episodic memory. Specifically, we show that when planning tasks
      are sorted according to the degree to which they evoke memories of personally
      familiar scenarios (e.g., planning a picnic), recall is reliably superior to
      tasks that fail to do so (e.g., planning an Arctic trek). We discuss the
      implications of these findings for planning tasks and their relation to episodic
      memory.

PMID- 21859234
TI  - Source-constrained recall: front-end and back-end control of retrieval quality.
AB  - Research on the strategic regulation of memory accuracy has focused primarily on
      monitoring and control processes used to edit out incorrect information after it
      is retrieved (back-end control). Recent studies, however, suggest that
      rememberers also enhance accuracy by preventing the retrieval of incorrect
      information in the first place (front-end control). The present study put forward
      and examined a mechanism called source-constrained recall (cf. Jacoby, Shimizu,
      Velanova, & Rhodes, 2005) by which rememberers process and use recall cues in
      qualitatively different ways, depending on the manner of original encoding.
      Results of 2 experiments in which information about source encoding depth was
      made available at test showed that when possible, participants constrained recall
      to the solicited targets by reinstating the original encoding operations on the
      recall cues. This reinstatement improved the quality of the information that came
      to mind, which, together with improved postretrieval monitoring, enhanced actual
      recall performance.

PMID- 21859235
TI  - Dynamic search and working memory in social recall.
AB  - What are the mechanisms underlying search in social memory (e.g., remembering the
      people one knows)? Do the search mechanisms involve dynamic local-to-global
      transitions similar to semantic search, and are these transitions governed by the
      general control of attention, associated with working memory span? To find out,
      we asked participants to recall individuals from their personal social networks
      and measured each participant's working memory capacity. Additionally,
      participants provided social-category and contact-frequency information about the
      recalled individuals as well as information about the social proximity among the
      recalled individuals. On the basis of these data, we tested various computational
      models of memory search regarding their ability to account for the patterns in
      which participants recalled from social memory. Although recall patterns showed
      clustering based on social categories, models assuming dynamic transitions
      between representations cued by social proximity and frequency information
      predicted participants' recall patterns best-no additional explanatory power was
      gained from social-category information. Moreover, individual differences in the
      time between transitions were positively correlated with differences in working
      memory capacity. These results highlight the role of social proximity in
      structuring social memory and elucidate the role of working memory for
      maintaining search criteria during search within that structure.

PMID- 21859236
TI  - Binary ROCs in perception and recognition memory are curved.
AB  - In recognition memory, a classic finding is that receiver operating
      characteristics (ROCs) are curvilinear. This has been taken to support the
      fundamental assumptions of signal detection theory (SDT) over discrete-state
      models such as the double high-threshold model (2HTM), which predicts linear
      ROCs. Recently, however, Broder and Schutz (2009) challenged this argument by
      noting that most of the data on which support for SDT is based have involved
      confidence ratings. The authors argued that certain types of rating scale usage
      may result in curved ROCs even if the generating process is thresholded in
      nature. From this point of view, only ROCs constructed via experimental bias
      manipulations are useful for discriminating between the models. Broder and Schutz
      conducted a meta-analysis and new experiments that compared SDT and the 2HTM
      using binary (yes-no) ROCs and found that many of these functions were linear,
      supporting 2HTM over SDT. We examine all the data reported by Broder and Schutz,
      noting important limitations in their methodology, analyses, and conclusions. We
      report a new meta-analysis and 2 new experiments to examine the issue more
      closely while avoiding the limitations of Broder and Schutz's study. These new
      data indicate that binary ROCs are curved in recognition, consistent with
      previous findings in perception and reasoning. Our results support classic
      arguments in favor of SDT and indicate that curvature in ratings ROCs is not task
      specific. We recommend the ratings procedure and suggest that analyses based on
      threshold models be treated with caution.

PMID- 21859237
TI  - Rural placement programs.

PMID- 21859239
TI  - Wonca: World Organization of National Colleges, Academies and Academic
      Associations of General Practitioners/Family Physicians.

PMID- 21859240
TI  - EGPRN: European General Practice Research Network.

PMID- 21859242
TI  - IPCRG: International Primary Care Respiratory Group.

PMID- 21859243
TI  - From the promising Canadian community health centres to the non-communicable
      diseases alliance global agenda: horizontal versus vertical developments!

PMID- 21859247
TI  - Gemcitabine, fludarabine and melphalan as a reduced-intensity conditioning
      regimen for allogeneic stem cell transplant in relapsed and refractory Hodgkin
      lymphoma: preliminary results.

PMID- 21859248
TI  - Cell cycle regulatory molecular profiles of pediatric T-cell lymphoblastic
      leukemia and lymphoma.
AB  - Proper regulation of the cell cycle plays a fundamental role in any organism, as
      it impacts cellular division, differentiation and death. In this intricate
      process, progression through the phases of the cell cycle relies on various
      cyclin-cyclin-dependent kinase protein complexes that are regulated by multiple
      cyclin-dependent kinase inhibitors. Ultimately, the transcription factor E2F is
      influenced by this cascade and regulates the mRNA levels of proteins needed for
      cell cycle progression. Thus, disturbance of cell cycle regulation has been shown
      to be responsible for various types of cancer including adult and pediatric T
      cell acute lymphoblastic leukemia and lymphoma (T-ALL and T-LBL, respectively),
      which are suggested to arise due to developmental arrest of precursor T
      lymphoblasts at certain early time points in T-cell maturation. Therapy
      optimization in recent years has resulted in good prognoses for patients of both
      malignancies. Here, we provide an overview of current knowledge of the cell cycle
      and its regulators with respect to pediatric T-ALL and T-LBL, both on molecular
      events underlying the disturbance of cell cycle regulation and on clinical
      parameters of affected children.

PMID- 21859249
TI  - Cryoglobulinemia in chronic hemodialysis patients.
AB  - BACKGROUND: Renal failure patients submitted to chronic hemodialysis can present
      with cryoglobulinemia. There are few studies on cryoglobulins in chronic
      hemodialysis patients. The aim of the present study was to determine the
      prevalence and to identify the components of cryoglobulins in chronic
      hemodialysis patients. METHODS: Fifty-four patients on chronic hemodialysis were
      evaluated for the presence of cryoglobulins, after inclusion and exclusion
      criteria. The components of the cryoprecipitate were analyzed. RESULTS:
      Cryoglobulins were detected in 83% (45/54) of the patients on chronic
      hemodialysis. The cryoprecipitate was constituted by IgG, IgM, IgA, and
      complement fractions C3 and C4. CONCLUSION: We concluded that there was a high
      prevalence of cryoglobulins in chronic hemodialysis patients, and the
      cryoprecipitate was constituted by IgG, IgM, IgA, and complement fractions C3 and
      C4.

PMID- 21859250
TI  - Esophageal perforation and mediastinitis after suicidal ingestion of 4.5% sodium
      hypochlorite [correction of hydrochlorite] bleach.
AB  - A 16-year-old woman deliberately drank 4.5% sodium hypochlorite bleach. She was
      transferred to the emergency department after gastric lavage was performed at a
      local clinic. She experienced chest pain and fever after several vomiting
      episodes and esophagoscopy. Chest computerized tomography (CT) revealed air
      bubbles and abnormal soft tissue density at the right lateral aspect of the mid
      esophagus, a small amount of complicated pleural effusion, and pneumothorax.
      Barium esophagography revealed abnormal leakage of contrast media at the right
      wall of the mid esophagus, which indicated acute mediastinitis. The patient
      received intensive care and underwent delayed esophageal repair and colonic
      transplant. She was discharged 12 weeks after admission.   Sodium hypochlorite is
      found in household bleaching agents used to disinfect dishes and bleach laundry.
      Poisoning due to ingestion of sodium hypochlorite bleach usually follows a benign
      clinical course. Few studies report severe complications such as esophageal
      stenosis or perforation.

PMID- 21859252
TI  - Getting to the heart of things in the field of cardiovascular gene therapy.

PMID- 21859253
TI  - Adeno-associated viral vector manufacturing: keeping pace with accelerating
      clinical development.

PMID- 21859254
TI  - What is a good journal?

PMID- 21859255
TI  - A unique case of neural amyloidoma diagnosed by mass spectrometry of formalin
      fixed tissue using a novel preparative technique.
AB  - We report here a unique amyloidoma of the radial nerve which could not be
      subtyped by available techniques, including immunohistochemistry and standard
      clinical and laboratory evaluation. In order to identify the amyloid monomer, we
      developed a novel preparative procedure designed to optimize conditions for
      liquid chromatography tandem mass spectrometry analysis of formalin
      fixed/paraffin-embedded (FFPE) tissue. Subsequent mass spectrometric analysis
      clearly identified kappa light chain as the monomer, with no evidence of lambda
      light chain. Manual interpretation of the matched spectra revealed no evidence of
      polyclonality. This study also enabled detailed characterisation of twelve likely
      amyloid matrix components. Finally, our analysis revealed extensive hydroxylation
      of collagen type I but, unexpectedly, an almost complete lack of hydroxylated
      residues in the normally heavily-hydroxylated collagen type VI chains, pointing
      to structural/functional alterations of collagen VI in this matrix that could
      have contributed to the pathogenesis of this very unusual tumour. Given the high
      quality of the data here acquired using a standard quadrupole-time of flight
      tandem mass spectrometer of modest performance, the robust and straightforward
      preparative method described constitutes a competitive alternative to more
      involved approaches using state-of-the-art equipment.

PMID- 21859257
TI  - Fatty acid composition and chemotaxonomic evaluation of species of Stachys.
AB  - The fatty acid composition of the seed oil of 23 Stachys taxa was analysed by
      GC/MS. The main compounds were found to be linoleic (27.1-64.3%), oleic (20.25
      48.1%), palmitic (4.3-9.1%), stearic (trace to 5.2%) and 6-octadecynoic (2.2
      34.1%) acids. The latter compound could be used as a chemotaxonomic marker of the
      genus Stachys. A cluster analysis was performed for comparison and
      characterisation of the seed oil from Stachys species.

PMID- 21859256
TI  - Virulence traits in Cronobacter species isolated from different sources.
AB  - Cronobacter spp. ( Enterobacter sakazakii ) includes gram-negative opportunistic
      foodborne pathogens known as rare but important causes of life-threatening
      neonatal infections. However, the pathogenic mechanism is not yet clear. In this
      study, 43 isolates of Cronobacter, from human and nonhuman sources, were
      analyzed. A total of four clusters were identified and 32 DNA pulsotypes were
      observed by pulsed-field gel electrophoresis. In addition, 86% of the Cronobacter
      isolates were able to adhere to HEp-2 cells and 35% were invasive, Cronobacter
      sakazakii isolates being the most efficient. Twenty-six percent of Cronobacter
      isolates were able to form biofilms, mainly those from nonhuman sources, such as
      Cronobacter dublinensis and Cronobacter malonaticus . Three putative virulence
      genes (siderophore-interacting protein (sip), type III hemolysin (hly), and
      plasminogen activator (cpa)) were identified by bioinformatic analysis and then
      detected by PCR. The sip gene was the most frequently detected (60%; 26/43),
      followed by the hly gene (37%; 16/43) and the cpa gene (28%; 12/43). The three
      genes were identified primarily in C. sakazakii. Our data show that Cronobacter
      species harbor different virulence traits.

PMID- 21859258
TI  - Essential oil composition of the fruits of Periploca laevigata Aiton subsp.
      angustifolia (Labill.) Markgraf (Apocynaceae - Periplocoideae).
AB  - The essential oil of the fruits of Periploca laevigata Aiton subsp. angustifolia
      (Labill.) Markgraf (Apocynaceae) from Lampedusa Island was obtained by
      hydrodistillation and its composition was analysed. The analyses allowed the
      identification and quantification of 64 volatile compounds belonging to different
      classes. The most abundant compounds were nonacosane, heptacosane, hentriacontane
      and delta-cadinene. Among the volatile compounds identified in the fruits of P.
      laevigata subsp. angustifolia, 31 are present in other taxa of Apocynaceae, 19
      have antimicrobial activity and four are pheromones for the butterfly Danaus
      chrysippus. The possible ecological role of the volatile compounds found is
      briefly discussed.

PMID- 21859259
TI  - California Lomatiums, Part X. Comparison of composition of the hydrodistilled
      oils from two subspecies of Lomatium mohavense.
AB  - The hydrodistilled oils from the fruits as well as the stems/leaves of Lomatium
      mohavense ssp. longilobum and Lomatium mohavense ssp. mohavense were analysed by
      GC and GC/MS. The respective oils from L. mohavense ssp. longilobum show (Z)-3
      hexenol at 9.3% and 7.5%, beta-sinensal at 18.8% and 6.8% and iso-alpha-sinensal
      at 18.9% and 19.3% as the major compounds. The corresponding oils from L.
      mohavense ssp. mohavense show beta-phellandrene/limonene at 12.2% and 6.0%, beta
      elemene at 1.8% and 17.8%, beta-caryophyllene at 8.9% and 7.8% and germacrene D
      at 18.8% and 10.8% as the predominant compounds.

PMID- 21859260
TI  - LC-ESI-MS characterisation of phytoalexins induced in chickpea and pea tissues in
      response to a biotic elicitor of Hypnea musciformis (red algae).
AB  - A simple extraction procedure and HPLC method was developed to analyse the major
      and minor components of induced phytoalexins of elicited tissues (seeds) of
      chickpeas (Cicer arietinum L.) and peas (Pisum sativum L.) treated with a biotic
      elicitor (k-carrageenan) of Hypnea musciformis (red algae) from the Karachi
      coast. The level and timing of the induced phytoalexin production were estimated
      on the basis of various elicitor dilutions and as a function of time; the results
      are presented and discussed. A LC-ESI-MS/MS technique has been employed for the
      detection and characterisation of the induced phytochemical components
      (flavonoids and their glyco-conjugates). Nine flavonoids were identified from
      chickpeas: naringin, naringin malonate, liquiritigenin, naringenin, biochanin A,
      daidzein, formononetin, maackiain and medicarpin, while five flavonoids were
      identified from peas: afrormosin, anhydropisatin, pisatin, pseudobaptigenin and
      maackiain. These compounds play a vital role as phytoalexins because of their
      antimicrobial activity.

PMID- 21859261
TI  - A new hydrochalcone from Miliusa sinensis.
AB  - A new dihydrochalcone 4',6'-dihydroxy-2',3',4-trimethoxydihydrochalcone (1) along
      with nine known compounds, pashanone (2), dihydropashanone (3), pinostrobin (4),
      5-hydroxy-7,4'-dimethoxyflavanone (5), 5-hydroxy-6,7-dimethoxyflavanone (6), 5
      hydroxy-7,8-dimethoxyflavanone (7), 24-methylencycloartane-3beta,21-diol (8),
      liriodenine (9) and 3,5-dihydroxy-7,3',4'-trimethoxyflavone (10), were isolated
      from the extracts, exhibiting cytotoxic activity (n-hexane and ethyl acetate
      extracts) of Miliusa sinensis. The structure of (1) was elucidated by the
      analysis of spectral data (IR, HR-MS, EI-MS, 1D and 2D NMR).

PMID- 21859262
TI  - In vitro accelerated mass propagation and ex vitro evaluation of Aloe vera L.
      with aloin content and superoxide dismutase activity.
AB  - An innovative protocol on accelerated in vitro propagation and acclimatisation
      was developed in Aloe vera L. Culture was initiated with rhizomatous stem where
      Murashige and Skoog (MS) medium fortified with 0.5 mg L(-1) alpha-naphthalene
      acetic acid and 1.5 mg L(-1) N(6)-benzylaminopurine (BAP) promoted earliest shoot
      induction. Maximum shoot multiplication was achieved in MS medium supplemented
      with 2.5 mg L(-1)BAP. The best in vitro rooting was observed in the MS medium
      with 0.5 mg L(-1) indole-3-acetic acid plus 2 g L(-1) activated charcoal. The
      simple acclimatisation process, primarily with a combination of sand and soil (1
      : 1 v/v) and finally with a blend of sand, soil and farm yard manure (2 : 1 : 1
      v/v), ensured a 98% survival rate. Overall, 192 true-to-type plantlets were
      achieved from a single explant within 85 days. Morphologically, in vitro
      generated plants performed better than conventionally propagated plants;
      nevertheless the similarity in aloin content, gel content and superoxide
      dismutase activity was corroborated.

PMID- 21859263
TI  - Acute lower respiratory infection in the developing world.

PMID- 21859264
TI  - The impact of an urban environment on a child's lungs.

PMID- 21859266
TI  - Pirfenidone in idiopathic pulmonary fibrosis: the CAPACITY program.
AB  - Idiopathic pulmonary fibrosis is the most lethal form of diffuse lung fibrosis,
      killing approximately half of those affected within 2-3 years of diagnosis. Until
      recently, no therapies had been shown to have an impact on disease progression.
      The Clinical Studies Assessing Pirfenidone (Esbriet((r))) in IPF: Research of
      Efficacy and Safety Outcomes (CAPACITY) program comprised two almost identical
      double-blind placebo-controlled studies assessing the effects of pirfenidone on
      change in forced vital capacity, the primary end point, over a 72-week period.
      One of these studies was positive, matching in magnitude the benefit seen in two
      previous positive Japanese studies. The other study did not meet its primary end
      point but positive trends were consistent in this and a number of secondary end
      point indices. Safety was acceptable, comprising mainly problems of tolerability
      rather than toxicity. It is likely that pirfenidone will be utilised in many
      countries as first-line therapy and will also be included in studies of
      combination therapy for this attritional disease.

PMID- 21859267
TI  - Screening of immigrants in the UK for latent tuberculosis.
AB  - Evaluation of: Pareek M, Watson JP, Ormerod LP et al. Screening of immigrants in
      the UK for imported latent tuberculosis: a multicentre cohort study and cost
      effectiveness analysis. Lancet Infect. Dis. 11(6), 435-444 (2011).Tuberculosis
      (TB) is a serious public health problem in the UK, and detection and prophylactic
      treatment of latent infection offers improved control. A recent study advocates
      the use of IFN-gamma release assays to detect latent TB infection in immigrants
      to the UK under 35 years of age and suggests that such a program would be most
      cost effective if targeted at new entrants from high burden countries. We discuss
      these findings in the light of recently updated UK and European guidelines. We
      conclude that while action to contain TB in the UK is urgently needed, further
      evidence is required to assess the impact and cost-effectiveness of screening
      algorithms for latent infection.

PMID- 21859268
TI  - Current status of regenerative replacement of the airway.
AB  - Tracheal replacement has been attempted since the beginning of the last century,
      but always failed because of the difficulties in harvesting and revascularizing
      its microvascular network and the necessity for heavy immunosuppression.
      Regenerative medicine is an emerging interdisciplinary field of research and
      clinical applications focused on the repair, replacement or regeneration of
      cells, tissues or organs to restore impaired function. Among the different
      regenerative medicine approaches, the application of scaffolds or matrices to
      grow new tissues or organs from isolated cells, tissue or synthetic compounds is
      the basic principle in tissue engineering. By doing so, immunosuppression is
      avoided. In this article, we describe the strategies that could have relevant
      clinical applications and the translational research approaches used to
      clinically replace irreversible diseases of the trachea, and discuss how to make
      this stem cell-based technology available to everyone.

PMID- 21859269
TI  - Optimizing knowledge of antiviral medications for prophylaxis and treatment of
      influenza during pregnancy.
AB  - Pregnant women are particularly susceptible to influenza-related morbidity and
      mortality and have historically been over-represented among patients with
      influenza, requiring hospitalization and intensive care unit admission. This has
      been observed during both nonpandemic and pandemic influenza seasons. During the
      H1N1 influenza pandemic of 2009-2010, pregnant women again had an increased
      likelihood of hospital or intensive care unit admission, and many deaths were
      documented. One identified risk factor for more severe disease was a delay in the
      initiation of antiviral medications. Vaccination is currently the most effective
      method for preventing severe influenza and its sequelae, and antiviral
      medications are used as an important adjunct to vaccination. Knowledge among
      pregnant women regarding influenza vaccine recommendations is poor, but by
      improving knowledge and understanding, vaccine rates can be increased. Although
      there are no published data examining knowledge regarding antiviral medications,
      one can hypothesize that knowledge is similarly low. In the current era, the
      appropriate use of vaccination and antiviral medications is the best defense
      against complications of influenza among pregnant women, and optimizing knowledge
      about these strategies among providers and patients alike is of paramount
      importance.

PMID- 21859270
TI  - Therapy for cough: where does it fall short?
AB  - Studies on cough have come a long way but many shortfalls still exist. These
      shortfalls can be attributed to: the lack of randomized controlled studies with a
      focus on cough; studies not using robust cough outcome measures, poor definition
      of target groups in studies and guidelines, the lack of safe and efficacious
      treatments; difficulty in defining etiological factors, and the lack of data on
      the predictors of response to therapies for cough dominant etiologies. Addressing
      shortfalls in cough therapy that focuses on improving the lives of people with
      cough requires a systematic approach that includes better medications, high
      quality studies, improved multidisciplinary guidelines and education (of both
      health professionals and patients). To achieve new cough therapeutics requires an
      improved understanding of cough in humans (i.e., not just in animals).
      Development of new medications without substantial adverse events is long awaited
      for cough.

PMID- 21859272
TI  - Lipids in cystic fibrosis.
AB  - Cystic fibrosis is characterized by severe intestinal and pulmonary symptoms, but
      also changes in the liver, pancreas and reproductive tract. Since
      gastrointestinal symptoms can be controlled, the quality of live and longevity of
      cystic fibrosis patients is mainly determined by pulmonary inflammation and
      chronic pulmonary infections with Pseudomonas aeruginosa, Staphylococcus aureus,
      Burkholderia cepacia and Haemophilus influenzae. Recent studies developed novel
      and exciting concepts regarding the pathogenesis and treatment of cystic
      fibrosis. In particular, several studies indicated a critical role of death
      receptors, caveolae proteins, membrane rafts, alterations of the ceramide
      metabolism with an accumulation of ceramide and a reduction of 15-keto
      prostaglandin 2 in cystic fibrosis lungs. These alterations have been found to be
      critically involved in the pulmonary inflammation and infection susceptibility of
      cystic fibrosis patients. However, albeit these studies provided novel insights
      into molecular mechanisms causing inflammation and vulnerability to infection,
      the details of these processes are still unknown.

PMID- 21859273
TI  - Effects of smoking cannabis on lung function.
AB  - Although cannabis (or marijuana) is the world's most widely-used illicit drug,
      there has been surprisingly little research into its effects on respiratory
      health. Part of the problem is the inherent difficulty of studying the long-term
      effects of an illegal habit. It has often been assumed that smoking cannabis will
      have similar long-term effects to smoking tobacco. Several recent observational
      studies suggest that this is not the case and that cannabis has quite different
      effects on the lung function. There are consistent findings that smoking cannabis
      is associated with large airway inflammation, symptoms of bronchitis, increased
      airway resistance and lung hyperinflation. The evidence that smoking cannabis
      leads to features of chronic obstructive pulmonary disease, such as airflow
      obstruction and emphysema is not convincing. However, there are numerous case
      reports of bullous emphysema among cannabis smokers. These findings have not been
      confirmed in systematic analytical studies and probably represent uncommon
      adverse effects in very heavy cannabis smokers. There is now additional
      controversial evidence that cannabis is at least an occasional cause of
      respiratory malignancies, but again the evidence is inconclusive.

PMID- 21859271
TI  - Progress in the development of human parainfluenza virus vaccines.
AB  - In children under 5 years of age, human parainfluenza viruses (HPIVs) as a group
      are the second most common etiology of acute respiratory illness leading to
      hospitalization, surpassed only by respiratory syncytial virus but ahead of
      influenza viruses. Using reverse genetics systems for HPIV serotypes 1, 2 and 3
      (HPIV1, 2 and 3), several live-attenuated HPIVs have been generated and evaluated
      as intranasal vaccines in adults and in children. Two vaccines against HPIV3 were
      found to be well tolerated, infectious and immunogenic in Phase I trials in HPIV3
      seronegative infants and children and should progress to proof-of-concept trials.
      Vaccines against HPIV1 and HPIV2 are less advanced and have just entered
      pediatric trials.

PMID- 21859274
TI  - Assessment and management of chronic obstructive pulmonary disease in the
      emergency department and beyond.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are
      common, can result in emergency department presentation and often result in
      hospitalization. After confirming the diagnosis and treating comorbidities,
      management of severe AECOPD includes bronchodilators, systemic corticosteroids,
      antibiotics, noninvasive ventilation and, occasionally, endotracheal intubation.
      Once discharged, delayed follow-up and suboptimal management often occurs.
      Antibiotics, systemic corticosteroids and optimization of nonpharmacological
      interventions (e.g., smoking cessation, immunization and pulmonary
      rehabilitation) are important discharge considerations. Improving linkages to
      primary providers who adhere to management involving a pharmacological and
      nonpharmacological evidence-based treatment plan is critical to preventing future
      AECOPDs, reducing healthcare utilization and maintaining the quality of life of
      patients following an AECOPD.

PMID- 21859275
TI  - Guidelines for aerosol devices in infants, children and adults: which to choose,
      why and how to achieve effective aerosol therapy.
AB  - Multiple types of aerosol devices are commonly used for the administration of
      medical aerosol therapy to patients with pulmonary diseases. All of these devices
      have been shown to be effective in trials where they are used correctly. However,
      failure to operate any of these devices properly has been associated with poor
      clinical response and limited patient adherence to therapy. Therefore, the
      selection of the best aerosol device for the individual patient is very important
      for optimizing the results of medical aerosol therapy. This article presents the
      rationale for selecting the most appropriate aerosol device to administer inhaled
      drugs in specific patient populations, with emphasis on patient-, drug-, device-
      and environment-related factors and with a comparison between the available
      devices. The following recommendations for the selection of the 'best' aerosol
      device for each patient population are intended to help clinicians gain a clear
      understanding of the specific issues and challenges so that they can optimize
      aerosol drug delivery and its therapeutic outcomes in patients.

PMID- 21859276
TI  - Diagnostic approach to sleep-disordered breathing.
AB  - Respiratory disorders in sleep are highly prevalent and increasingly recognized.
      Among these, obstructive sleep apnea, resulting in daytime fatigue and
      somnolence, increased risk of workplace and traffic accidents but also
      psychosocial dysfunction, is most often diagnosed. As an independent risk factor
      for cardiovascular and metabolic disease, obstructive sleep apnea has recently
      attracted even more attention. Apart from continuous positive airway pressure,
      only a few alternative treatment options are available. Individual history is
      still most important for selecting patients for sleep studies. Fatigue and a high
      subjective propensity to fall asleep during the daytime, a history of snoring and
      breathing pauses during sleep combined with anthropometric risk factors make a
      diagnosis very likely. Other night-time respiratory disorders include central
      sleep apnea, Cheyne-Stokes respiration, obesity hypoventilation syndrome and
      mixed sleep apnea syndromes. The diagnosis of sleep-disordered breathing can be
      made by comprehensive sleep studies in a sleep laboratory, but also using
      portable equipment for cardiorespiratory monitoring and measurement of oxygen
      desaturation at home, according to pretest probabilities, individual experience
      and local preferences.

PMID- 21859278
TI  - Hypoxia impedes vasculogenesis of in vitro engineered bone.
AB  - To ensure the survival of engineered bone after implantation, we combined human
      endothelial colony forming cells (ECFCs) and multipotent stromal cells (MSCs) as
      a proof of concept in a co-culture model to create in vitro prevascularized bone
      constructs. We hypothesized that a hypoxic stimulus will contribute to
      prevascularization of engineered bone. Bone marrow-derived MSCs and ECFCs from
      human adult peripheral blood were allowed to form co-culture pellets containing
      ECFCs and MSCs (1:4) or MSCs only in controls. After culture under normoxia or
      hypoxia (5%), pellets were harvested and processed for immunohistochemistry of
      CD31, alpha-smooth muscle actin, and osteocalcin. Expression of vascular
      endothelial growth factor and SDF-1alpha was analyzed by PCR to elucidate their
      involvement in hypoxic stimulation of prevascularization. The normoxic condition
      in co-cultures of MSCs and ECFCs supported the formation and maintenance of
      prevascular structures, including organized CD31-positive cells embraced by
      differentiated mural cells. These structures failed to form in hypoxic
      conditions, thereby rejecting the hypothesis that hypoxia stimulates
      prevasculogenesis in three-dimensional engineered bone constructs. Further, the
      formation of prevascular structures was paralleled by increased SDF-1alpha
      expression. It is suggested that actual oxygen levels were below 5% in the
      hypoxic co-cultures, which prevented prevascular structure formation. In
      conclusion, our normoxic co-culture model containing cells from clinically
      relevant sources sustained simultaneous endothelial, smooth muscle, and
      osteogenic differentiation.

PMID- 21859279
TI  - Trauma-related dreams of Australian veterans with PTSD: content, affect and
      phenomenology.
AB  - OBJECTIVE: Consensus on the parameters of trauma-related dreams required to meet
      criteria for post-traumatic stress disorder (PTSD) is critical when: (i) the
      diagnosis requires a single re-experiencing symptom; and (ii) trauma dreams are
      prevalent in survivors without PTSD. METHOD: This study investigated the
      phenomenology of PTSD dreams in 40 veterans, using structured interview and self
      report measures. RESULTS: Dream content varied between replay, non-replay, and
      mixed, but affect was largely the same as that experienced at the time of trauma
      across all dream types. ANOVA indicated no difference between dream types on PTSD
      severity or nightmare distress. CONCLUSIONS: The findings provide preliminary
      support for non-replay dreams to satisfy the DSM B2 diagnostic criterion when the
      affect associated with those dreams is the same as that experienced at the time
      of the traumatic event.

PMID- 21859280
TI  - The Adult Attachment Projective Picture System: integrating attachment into
      clinical assessment.
AB  - This article summarizes the development and validation of the Adult Attachment
      Projective System (AAP), a measure we developed from the Bowlby-Ainsworth
      developmental tradition to assess adult attachment status. The AAP has
      demonstrated excellent concurrent validity with the Adult Attachment Interview
      (George, Kaplan, & Main, 1984/1985/1996; Main & Goldwyn, 1985-1994; Main,
      Goldwyn, & Hesse, 2003), interjudge reliability, and test-retest reliability,
      with no effects of verbal intelligence or social desirability. The AAP coding and
      classification system and application in clinical and community samples are
      summarized. Finally, we introduce the 3 other articles that are part of this
      Special Section and discuss the use of the AAP in therapeutic assessment and
      treatment.

PMID- 21859281
TI  - Use of the Adult Attachment Projective Picture System in an assessment of an
      adolescent in foster care.
AB  - Child maltreatment has been associated with a host of negative outcomes including
      impaired social relationships (Rogosch, Cicchetti, & Aber, 1995), depression
      (Toth, Manly, & Cicchetti, 1992), poor self-concept and motivation (Vondra,
      Barnett, & Cicchetti, 1990), and delinquency and conduct problems (Cook et al.,
      2005; Grotevant et al., 2006; McCabe, Lucchini, Hough, Yeh, & Hazen, 2005; Ryan &
      Testa, 2005). An assessment of the mental representation of attachment
      relationships could offer additional relevant and useful information to the
      evaluation of youth in foster care, and could inform treatment and placement
      considerations. The Adult Attachment Projective Picture System (AAP) is a
      relatively new measure of internal representations of attachment based on the
      analysis of a set of stimuli designed to systematically activate the attachment
      system (George, West, & Pettem, 1997). This article considers the use of the AAP
      with a maltreated adolescent in a clinical setting and uses a case study to
      illustrate the components of the AAP that are particularly relevant to case
      conceptualization and interventions.

PMID- 21859282
TI  - Use of the Adult Attachment Projective Picture System (AAP) in the middle of a
      long-term psychotherapy.
AB  - This article relates how the Adult Attachment Projective Picture System (AAP) was
      used as a midtherapy intervention with a middle-aged man being treated for
      relationship difficulties. The man, who was identified via the AAP as having a
      dismissing attachment status, had difficulties committing to psychotherapy,
      presumably because he was terrified of experiencing the underlying depression and
      grief revealed on his Rorschach and AAP. Reading an AAP-based description of his
      attachment status helped the man become aware of his characteristic defenses
      against painful affect, and gave him the motivation to stay in therapy while
      experiencing and getting support for his unresolved mourning. This work led to
      the man's experiencing less ambivalence about intimate relationships. There are
      several important ways that the AAP augments a traditional personality assessment
      battery and is useful in conducting a long-term psychotherapy.

PMID- 21859283
TI  - Attachment, assessment, and psychological intervention: a case study of anorexia.
AB  - Attachment patterns and personality dimensions have always been considered
      important to the development and adaptation of the individual. The first aim of
      this article was to address some basic questions about the place of attachment in
      a multimethod assessment when compiling a complete picture of the patient's
      personality functioning. The second aim was to present the Adult Attachment
      Projective Picture System (AAP; George & West, 2001) as a valid and productive
      assessment measure. Based on a single case study of an anorexic young woman, the
      article demonstrates how the AAP is integrated with the Rorschach Comprehensive
      System (Exner, 1991, 1993) and other assessment tools in both the assessment and
      in developing a treatment plan.

PMID- 21859284
TI  - The relationship between unstandardized and standardized alpha, true reliability,
      and the underlying measurement model.
AB  - Popular computer programs print 2 versions of Cronbach's alpha: unstandardized
      alpha, alpha(Sigma), based on the covariance matrix, and standardized alpha,
      alpha(R), based on the correlation matrix. Sources that accurately describe the
      theoretical distinction between the 2 coefficients are lacking, which can lead to
      the misconception that the differences between alpha(R) and alpha(Sigma) are
      unimportant and to the temptation to report the larger coefficient. We explore
      the relationship between alpha(R) and alpha(Sigma) and the reliability of the
      standardized and unstandardized composite under 3 popular measurement models; we
      clarify the theoretical meaning of each coefficient and conclude that researchers
      should choose an appropriate reliability coefficient based on theoretical
      considerations. We also illustrate that alpha(R) and alpha(Sigma) estimate the
      reliability of different composite scores, and in most cases cannot be
      substituted for one another.

PMID- 21859285
TI  - Disentangling prototypicality and social desirability: the case of the KNOWI
      task.
AB  - The prototype of indicators of a relationship partner who can be trusted to be
      responsive at times of stress is one kind of social knowledge structure. The
      Knowledge of Indicators (KNOWI) Task assesses individual differences in knowledge
      about these prototypic indicators. In constructing the KNOWI, an iterative
      procedure was used in an attempt to identify those indicators for which ratings
      of prototypicality are not influenced by social desirability. Study 1
      demonstrated that the correlation between ratings of prototypicality and social
      desirability is indeed eliminated for the final set of indicators retained in the
      KNOWI. Study 2 tested the prototype matching hypothesis: Comparing an actual
      partner to the prototype might shape global judgments about that partner's
      responsiveness. Because in Study 2 only those indicators that are uncorrelated
      with social desirability were used, this result cannot be explained by social
      desirability. These results support the construct validity of the indicators used
      in the KNOWI Task, which seems to be a precise assessment tool not influenced by
      social desirability.

PMID- 21859286
TI  - The construction and validation of a measure of Ethno-cultural Identity Conflict.
AB  - The research describes the construction and validation of the Ethno-cultural
      Identity Conflict Scale (EICS) based on 3 independent samples totaling 975
      immigrants, international students, and members of ethnic minority groups. The
      convergent validity of the 20-item scale was supported by its correlations with
      Self-Concept Clarity (r = -.65), Sense of Coherence (r = -.58), Identity Distress
      (r = .48), and the Cultural Conflict (r = .62) and Cultural Distance (r = .21)
      components of the Bicultural Identity Integration Scale. EICS was also linked to
      contemporary acculturation research with integrated migrants experiencing less
      conflict than those who were separated, assimilated, or marginalized.

PMID- 21859287
TI  - Psychometric properties and clinical cut-off scores of the Spanish version of the
      Social Anxiety Scale for Adolescents.
AB  - This study examined the reliability and validity evidence drawn from the scores
      of the Spanish version of the Slovenian-developed Social Anxiety Scale for
      Adolescents (SASA; Puklek, 1997; Puklek & Vidmar, 2000) using a community sample
      (Study 1) and a clinical sample (Study 2). Confirmatory factor analysis in Study
      1 replicated the 2-factor structure found by the original authors in a sample of
      Slovenian adolescents. Test-retest reliability was adequate. Furthermore, the
      SASA correlated significantly with other social anxiety scales, supporting
      concurrent validity evidence in Spanish adolescents. The results of Study 2
      confirmed the correlations between the SASA and other social anxiety measures in
      a clinical sample. In addition, findings revealed that the SASA can effectively
      discriminate between adolescents with a clinical diagnosis of social anxiety
      disorder (SAD) and those without this disorder. Finally, cut-off scores for the
      SASA are provided for Spanish adolescents.

PMID- 21859288
TI  - The development of the 2-Way Social Support Scale: a measure of giving and
      receiving emotional and instrumental support.
AB  - A number of studies support the refinement of various types of social support
      into 2 primary dimensions: emotional support and instrumental support. There is
      increasing recognition of benefits aligned with giving as well as receiving
      social support, yet there has been no single measure published that incorporates
      all of these elements. This study presents the development of the 2-Way Social
      Support Scale (2-Way SSS) using community samples (n = 372; n = 417) and provides
      evidence for the scales' factor structure, reliability, and validity. The 2-Way
      SSS concurrently appraises 4 principal dimensions: (a) giving emotional support,
      (b) giving instrumental support, (c) receiving emotional support, and (d)
      receiving instrumental support. The completeness of the scale, combined with the
      generic quality of the items, enhances its utility across a diversity of
      contexts. Importantly, this scale provides a measurement tool that will enable
      the comparison of social support research outcomes across studies and
      populations.

PMID- 21859289
TI  - Reliability of self-reported attachment style in patients with severe
      psychopathology.
AB  - Little is known about whether severe psychopathology influences the assessment of
      self-reported attachment style. Fifty-eight randomly selected adult psychiatric
      inpatients completed the Experiences in Close Relationship questionnaire (ECR;
      Brennan, Clark, & Shaver, 1998) and were administered the 24-item Brief
      Psychiatric Rating Scale (BPRS; Ventura et al., 1993) and the Hamilton Depression
      Rating Scale (HDRS; Hamilton, 1960) at both admission and discharge. The
      Structured Clinical Interview for DSM-IV (SCID-I; First, Spitzer, Gibbon, &
      Williams, 1996) was used to establish Axis I diagnoses. The ECR scales showed
      good internal consistency and absolute stability both in patients with (n = 24)
      and without (n = 34) a psychotic disorder. Relative stability was only fair among
      patients with psychotic disorders but good among patients without psychotic
      disorders. Neither higher BPRS or HDRS scores, nor the presence of a psychotic
      disorder, significantly reduced the retest reliability of the ECR scales. These
      findings suggest that self-report measures might provide a reliable assessment of
      attachment style in patients with severe psychopathology, except for the most
      severely impaired patients.

PMID- 21859290
TI  - Psychometric characteristics of Carver and White's BIS/BAS scales in Dutch
      adolescents and their mothers.
AB  - The psychometric characteristics of Carver and White's (1994) BIS/BAS scales were
      examined in 2 groups of Dutch adolescents (497 early adolescents and 237 middle
      adolescents, M (Age) = 13.0 years and 16.4 years, respectively) and their middle
      aged mothers (M (Age) = 45.2 years; N = 734). Confirmatory factor analyses
      revealed an acceptably fitting 2-factor model for adapted BIS /BAS scales in all
      3 groups, reflecting separate BIS and BAS factors. Reliabilities of the 2 scales
      were satisfactory. The results supported the convergent validity of BIS and BAS
      scales. BIS was positively correlated with internalizing problem behaviors and
      neuroticism. BAS was positively correlated with externalizing problem behaviors
      and extraversion. The discriminant validity of the BIS/BAS scales received mixed
      support in our data. BIS was negatively correlated with extraversion, and BAS was
      not correlated with depression. However, BIS was also found to be correlated with
      externalizing problem behaviors, and BAS was positively correlated with
      neuroticism. In sum, the scales are suitable for use in research settings, but
      caution is advocated in application for clinical practice.

PMID- 21859291
TI  - Associations between Symptom Validity Test failure and scores on the MMPI-2-RF
      validity and substantive scales.
AB  - This study examined the association between Symptom Validity Test (SVT) failure
      and the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2
      RF; Ben-Porath & Tellegen, 2008), in the Forensic Disability Claimant samples
      described in the MMPI-2-RF Technical Manual (Tellegen & Ben-Porath, 2008 a,
      2008b). SVTs used included the Word Memory Test (Green, 2003), the Computerized
      Assessment of Response Bias (Allen, Conder, Green, & Cox, 1997), the Medical
      Symptom Validity Test (Green, 2004), and the Test of Memory Malingering
      (Tombaugh, 1996). SVT failure was associated with significant elevations
      throughout the MMPI-2-RF overreporting validity scales and substantive scales.
      Pairwise contrasts between groups failing 0 and 3 SVTs revealed predominantly
      large effect sizes for the overreporting validity scales (d = 0.78-1.11), and
      many of the substantive scales, including the Cognitive Complaints (COG) scale.
      Results of this study demonstrate an association between SVT performance and
      elevated scores on the MMPI-2-RF. These results suggest that exaggeration of
      cognitive symptoms as demonstrated by SVT failure is also associated with
      overreported emotional, somatic, and neurocognitive complaints on the MMPI-2-RF.

PMID- 21859293
TI  - Parent-child discrepancies in report of psychopathology: the contributions of
      response bias and parenting stress.
AB  - This study explored the associations between response-bias features, parenting
      stress, and parent-child discrepancies in self-report and parent ratings of
      psychopathology in a sample of 153 preadolescents from an inpatient psychiatric
      setting. Correlational and multiple regression analyses utilized combinations of
      dissimulation (FB) and defensiveness (DEF) validity scales from the Personality
      Inventory for Youth (PIY; Lachar & Gruber, 1995) and Personality Inventory for
      Children (PIC-2; Lachar & Gruber, 2001) and components from Abidin's (1995)
      Parenting Stress Index (PSI) to predict normalized parent-child discrepancies
      between the PIY/PIC-2 clinical scales. Response-bias features were significantly
      associated with hypothesized patterns of under- and overreporting and accounted
      for most of the variance in parent-child discrepancies. Although child stress
      components of the PSI demonstrated a generalized pattern of moderate
      relationships with parent-child discrepancies, parent stress components
      demonstrated a weaker and more specific pattern of relationships.

PMID- 21859292
TI  - Appraisal of suicidal risk among adolescents and young adults through the
      Rorschach test.
AB  - The aims of this study are to investigate suicidal behaviors among adolescents
      and young adults and to test an index composed using Rorschach test responses
      related to an increased risk of suicide. Using a cross-sectional design, 4 groups
      were studied (according to criteria of the Columbia Classification Algorithm of
      Suicide Assessment [Posner, Oquendo, Gould, Stanley, & Davies, 2007]): A group
      with suicidal ideation (n = 30), a group with parasuicidal behavior (n = 30), a
      group with near-lethal suicide attempts (n = 26), and a control group (n = 30).
      Responses to the Rorschach test yielded 6 potential indicators of suicidal
      behavior (scored according to Exner's Comprehensive System and the Suicidal Index
      for Adolescents; Silberg & Armstrong, 1992 ). Rorschach scores including at least
      4 of these 6 indicators selected 69% of the people who had committed serious
      suicide attempts. The Rorschach Suicidal Index reached an acceptable reliability
      and was related to other criteria of suicide risk, such as the Beck Depression
      Inventory (BDI; Beck, Ward, Mendelsohn, Mock, & Erbaugh, 1961) and Linehan
      Reasons for Living Inventory (RFL-I; Linehan, Goodstein, Nielsen, & Chiles,
      1983). Moreover, the Rorschach Suicidal Index showed incremental validity over
      the BDI and the RFL-I to predict suicidal behavior. A path analysis additionally
      showed that low social support was an important mediator between the Rorschach
      Suicidal Index and the number of suicide attempts committed by participants.

PMID- 21859295
TI  - Antibacterial properties of a glycolipid-rich extract and active principle from
      Nunavik collections of the macroalgae Fucus evanescens C. Agardh (Fucaceae).
AB  - This study investigated the antibacterial activity of glycolipid-rich extracts of
      the brown macroalga Fucus evanescens in cell culture. Accessions were collected
      on the Arctic coast of Ungava Bay, Nunavik, Quebec. The crude ethyl acetate
      extract of these accessions showed strong antibacterial activity (>=4 log(10)
      cfu) against Hemophilus influenzae , Legionella pneumophila , Propionibacterium
      acnes (ATCC and clinical isolate), and Streptococcus pyogenes at 100 ug/mL. This
      algal extract inhibited by 3 log(10) Clostridium difficile and methicillin
      resistant Staphylococcus aureus , whereas Bacillus cereus , Escherichia coli ,
      Klebsiella pneumoniae , and Pseudomonas aeruginosa were not significantly
      affected. Further investigations of the activity of a glycolipid-rich fraction,
      extracted with dichloromethane, against Propionibacterium acnes showed an
      MIC(100) of 50 ug/mL, with an inhibition of more than 99% at only 7.8 ug/mL. The
      main active compound, a beta-d-galactosyl O-linked glycolipid, was synthesized
      for the bioassay and showed an MIC(100) of 50 ug/mL but lost its activity more
      quickly with only 50% of inhibition at 12.5 ug/mL. Therefore, the semipurified F.
      evanescens extract could be a good choice for future research into the
      development of alternative treatments for acne therapy.

PMID- 21859296
TI  - Drugs for neglected diseases: part I.

PMID- 21859298
TI  - Interview with James McKerrow.
AB  - James McKerrow's research interests focus on the biology of the host-parasite
      relationship, from primitive single-cell protozoa to complex multicellular
      bloodflukes. His group employs techniques from a variety of disciplines to
      develop new drugs for parasitic diseases. He speaks to Future Medicinal Chemistry
      about what inspired him to enter research and offers his take on the state of the
      neglected diseases R&D landscape.

PMID- 21859299
TI  - The TB Alliance: overcoming challenges to chart the future course of TB drug
      development.
AB  - The Global Alliance for TB Drug Development (TB Alliance) is a not-for-profit
      organization dedicated to the discovery and development of faster-acting and
      affordable drugs to fight TB. TB kills nearly 2 million people each year, partly
      due to the inadequacy of the current treatment. There have been no new drugs
      registered for TB in more than 40 years, but new partnership models over the past
      decade have enabled tremendous progress in the pipeline. With 10 clinical
      compounds now in development globally, the TB Alliance is embarking on a new
      paradigm of clinical development, one that leverages both new and existing
      compounds to discover and develop markedly shorter, simpler, faster-acting and
      less toxic multidrug regimens that can treat both drug-sensitive and multidrug
      resistant TB concurrently, dramatically simplifying treatment and facilitating
      the scale-up of global treatment efforts.

PMID- 21859300
TI  - From bench to clinic: bridging the translational gap in neglected disease drug
      development.

PMID- 21859301
TI  - Benzoxaboroles: a new class of potential drugs for human African trypanosomiasis.
AB  - Human African trypanosomiasis, caused by the kinetoplastid parasite Trypanosoma
      brucei, affects thousands of people across sub-Saharan Africa, and is fatal if
      left untreated. Treatment options for this disease, particularly stage 2 disease,
      which occurs after parasites have infected brain tissue, are limited due to
      inadequate efficacy, toxicity and the complexity of treatment regimens. We have
      discovered and optimized a series of benzoxaborole-6-carboxamides to provide
      trypanocidal compounds that are orally active in murine models of human African
      trypanosomiasis. A key feature of this series is the presence of a boron atom in
      the heterocyclic core structure, which is essential to the observed trypanocidal
      activity. We also report the in vivo pharmacokinetic properties of lead compounds
      from the series and selection of SCYX-7158 as a preclinical candidate.

PMID- 21859302
TI  - Drug discovery for neglected tropical diseases at the Sandler Center.
AB  - The Sandler Center's approach to target-based drug discovery for neglected
      tropical diseases is to focus on parasite targets that are homologous to human
      targets being actively investigated in the pharmaceutical industry. In this way
      we attempt to use both the know-how and actual chemical matter from other drug
      development efforts to jump start the discovery process for neglected tropical
      diseases. Our approach is akin to drug repurposing, except that we seek to
      repurpose leads rather than drugs. Medicinal chemistry can then be applied to
      optimize the leads specifically for the desired antiparasitic indication.

PMID- 21859304
TI  - Target repurposing for neglected diseases.
AB  - Infectious diseases are an enormous burden to global health and ,since drug
      discovery is costly, those infectious diseases that affect the developing world
      are often not pursued by commercial drug-discovery efforts. Therefore, pragmatic
      means by which new therapeutics can be discovered are needed. One such approach
      is target repurposing, where pathogen targets are matched with homologous human
      targets that have been pursued for drug discovery for other indications. In many
      cases, the medicinal chemistry, structural biology and biochemistry knowledge
      around these human targets can be directly repurposed to launch and accelerate
      new drug-discovery efforts against the pathogen targets. This article describes
      the overarching strategy of target repurposing as a tool for initiating and
      prosecuting neglected disease drug-discovery programs, highlighting this approach
      with three case studies.

PMID- 21859305
TI  - Developing novel antisecretory drugs to treat infectious diarrhea.
AB  - Diarrhea, a disease of poverty and poor sanitation, kills an estimated two
      million children each year. Oral rehydration therapy is a very simple and
      inexpensive treatment that has significantly reduced mortality from secretory
      diarrhea caused by rotavirus, cholera and enterotoxigenic Escherichia coli. The
      efficacy and adoption of oral rehydration therapy would be enhanced by a drug
      that reduces fluid loss associated with these diseases and alleviates disease
      symptoms. Secretion and absorption by the intestine offer a number of potential
      drug targets to reduce fluid loss. Among these, the cystic fibrosis transmembrane
      conductance regulator (CFTR) chloride channel is the most attractive because it
      is the primary driver of secretion in cases of diarrhea caused by enterotoxigenic
      bacteria. CFTR can be inhibited by both natural products and synthetic small
      molecules. iOWH032 is a synthetic CFTR inhibitor that has recently entered
      clinical trials for this indication.

PMID- 21859303
TI  - Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs:
      exploiting the benefit of enzymes that are highly conserved between host and
      parasite.
AB  - Protozoan infections remain a major unsolved medical problem in many parts of our
      world. A major obstacle to their treatment is the blatant lack of medication that
      is affordable, effective, safe and easy to administer. For some of these
      diseases, including human sleeping sickness, very few compounds are available,
      many of them old and all of them fraught with toxic side effects. We explore a
      new concept for developing new-generation antiprotozoan drugs that are based on
      phosphodiesterase (PDE) inhibitors. Such inhibitors are already used extensively
      in human pharmacology. Given the high degree of structural similarity between the
      human and the protozoan PDEs, the vast expertise available in the human field can
      now be applied to developing disease-specific PDE inhibitors as new antiprotozoan
      drugs.

PMID- 21859307
TI  - Acute hepatitis C virus in an HIV clinic: a screening strategy, risk factors, and
      perception of risk.
AB  - Acute hepatitis C virus (HCV) infection is being acquired undetected among HIV
      infected individuals. A practical way to regularly screen HIV-infected patients
      for acute HCV irrespective of perceived risk or symptoms is needed. We piloted
      implementation of an acute HCV screening strategy using routine HIV clinical care
      schedules and the least costly blood tests, in a Rhode Island HIV care center.
      Study participants had ongoing HCV risk, completed questionnaires encompassing
      risk behaviors and perception of risk, and were screened with quarterly alanine
      aminotransferase (ALT). ALT rise triggered HCV RNA testing, with pooled rather
      than individual specimen HCV RNA testing for underinsured participants.
      Participants were primarily older, college-educated men who have sex with men
      (MSM) with history of sexually transmitted infection other than HIV. One of 58
      participants developed acute HCV in 50 person-years of observation for an annual
      incidence of 2.0% per year (95% confidence interval [CI] 0.05-11.1%). The
      majority (54%) of MSM did not perceive that traumatic sexual and drug practices
      they were engaging in put them at risk for HCV. Unprotected sex often occurred
      under the influence of drugs or alcohol. Self-reported HCV risk and participation
      in several risk behaviors declined during the study. It was possible to collect
      frequent ALTs in a busy HIV clinic with 71% of total projected ALTs obtained and
      88% of participants having at least one ALT during the 9-month follow-up period.
      All instances of ALT rise led to reflexive HCV RNA testing. Tracking quarterly
      ALT for elevation to systematically prompt HCV RNA testing before seroconversion
      is a promising approach to screen for acute HCV in a real-world HIV clinical
      setting.

PMID- 21859308
TI  - Is laparoscopic extirpation of the cervical stump after laparoscopic
      supracervical hysterectomy justified in women with incidentally found atypical
      endometrial hyperplasia?
AB  - OBJECTIVE: An incidental finding of atypical endometrial hyperplasia (AEH) in
      women who have undergone laparoscopic supracervical hysterectomy (LASH) is a rare
      phenomenon, and it is unclear whether laparoscopic extirpation of the cervical
      stump (LECS) is justified in these patients. METHODS: LECS due to AEH found
      incidentally in the morcellated uterus after LASH. RESULTS: A total of 332 women
      underwent LASH between January 2002 and September 2010. Five of the women (1.5%)
      underwent secondary LECS procedures due to histological evidence of AEH or focal
      atypical endometrial cells found incidentally in the morcellated uterus. No
      atypical endometrial cells were histologically diagnosed in the cervical stump in
      any of the cases, nor were any endometrial cells found in the cervical stumps in
      any of the 5 patients. There was no abdominal evidence at all of any disseminated
      endometrial cells. In all 5 cases, cytological examination of peritoneal fluid
      confirmed the absence of adenocarcinoma cells. CONCLUSIONS: No signs of AEH were
      found in the removed cervical stumps. However, women should receive counseling
      regarding the need for secondary LECS to minimize any risks in such cases.

PMID- 21859309
TI  - Emergency laparoscopic-assisted right hemicolectomy: can we achieve outcomes
      similar to elective operation?
AB  - The aim of this study was to compare short-term clinical outcomes of elective and
      emergency laparoscopic-assisted right hemicolectomy. Between January 2005 and
      December 2009, 181 patients had laparoscopic-assisted right hemicolectomy
      performed at our institute (148 elective and 33 emergency cases). The demographic
      data, operative details, and short-term outcomes were collected. There were 104
      men and 77 women. The median age was 69 years (range, 22-88 years). The
      demographic data of the 2 groups were similar except the patients were younger in
      the emergency surgery group (60 vs. 69 years; P=.02). The operating time of the
      emergency group was significantly longer then the elective group (165 vs. 150
      minutes; P<.001) but the intraoperative blood loss was similar. The postoperative
      complication and recovery were similar between the 2 groups. In selected clinical
      settings, emergency laparoscopic-assisted right hemicolectomy can be safely
      performed without worsening the clinical outcomes.

PMID- 21859310
TI  - Laparoscopic Nissen versus Toupet fundoplication: assessment of operative
      outcomes.
AB  - BACKGROUND: This study was designed to analyze the outcomes of Nissen
      fundoplication (NF) versus Toupet fundoplication (TF) in patients undergoing
      laparoscopic antireflux surgery (LARS). METHODS: All perioperative data,
      operative/postoperative complications, and follow-up data were prospectively
      recorded. All patients were seen on the 2nd month postoperatively and by yearly
      intervals thereafter. All patients have at least 12-month follow-up. Using SPSS
      software, groups were compared by t-test and chi-square tests as appropriate.
      RESULTS: One thousand consecutive patients underwent primary LARS from May 2004
      to August 2009. Six hundred eighty-four patients had NF and 316 had TF
      fundoplication. The mean follow-up of the NF (51.26 months) group was slightly
      longer than the TF group (43.53 months) (P=.018). There was no mortality and
      conversion. Esophageal perforation, jejunal perforation, and pulmonary emboli
      were the sole three major complications in separate patients. Dysphagia occurred
      in 15.4% and 9.9% in NF and TF, respectively (P=.001). Corresponding numbers for
      bloating were 19.6% and 10.8% in NF and TF, respectively (P=.001). Seventeen
      patients underwent reinterventions such as dilatation and re-do surgery and all
      17 were in the NF group (P<.05). All other minor complications were similar
      except hiccups, which were seen in 30 patients and all were in the NF group
      (P<.05). Recurrence of reflux was observed in 1.8% and 2.2% of the NF and TF,
      respectively (P=.620). CONCLUSION: Both NF and TF are effective procedures in
      controlling the acid-reflux symptoms. The functional side effects appear more
      often in the NF group. These side effects can be minimized and reinterventions
      for severe/prolonged dysphagia can be avoided with TF.

PMID- 21859312
TI  - Effects of pH values of hydrogen peroxide bleaching agents on enamel surface
      properties.
AB  - This study investigated the influence of pH values of bleaching agents on the
      properties of the enamel surface. Sixty freshly extracted premolars were embedded
      in epoxy resin and mesiodistally sectioned through the buccal aspect into two
      parts. The sectioned slabs were distributed among six groups (n=10) and treated
      using different solutions. Group HCl was treated with HCl solution (pH=3.0) and
      served as a positive control. Group DW, stored in distilled water (pH=7.0),
      served as a negative control. Four treatment groups were treated using 30%
      hydrogen peroxide solutions with different pH values: group HP3 (pH=3.0), group
      HP5 (pH=5.0), group HP7 (pH=7.0), and group HP8 (pH=8.0). The buccal slabs were
      subjected to spectrophotometric evaluations. Scanning electron microscopy
      investigation and Micro-Raman spectroscopy were used to evaluate enamel surface
      morphological and chemical composition alterations. pH value has a significant
      influence on the color changes after bleaching (p<0.001). Tukey's multiple
      comparisons revealed that the order of color changes was HP8, HP7>HP5,
      HP3>HCl>DW. No obvious morphological alterations were detected on the enamel
      surface in groups DW, HP7, and HP8. The enamel surface of groups HCl and HP3
      showed significant alterations with an erosion appearance. No obvious chemical
      composition changes were detected with respect to Micro-Raman analysis. Within
      the limitations of this study, it was concluded that no obvious morphological or
      chemical composition alterations of enamel surface were detected in the neutral
      or alkaline bleaching solutions. Bleaching solutions with lower pH values could
      result in more significant erosion of enamel, which represented a slight
      whitening effect.

PMID- 21859313
TI  - An in vitro assessment of the effects of three surface treatments on repair bond
      strength of aged composites.
AB  - OBJECTIVE: This study evaluated the effectiveness of three surface treatments on
      repair shear bond strength (SBS) of aged composites. METHODS: A total of 120
      cylindrical samples made of a micro-hybrid composite (Clearfil AP-X) were
      randomly assigned to one control and three experimental groups (n=30) after water
      storage (3 weeks). All experimental groups included surface roughening with
      diamond burs. Subsequent treatments were provided as follows: group 1 - only
      (self-etching) bonding; group 2 - silane and bonding; and group 3 - phosphoric
      acid etching, silane, and bonding. The composites were repaired with the same
      brand and were aged (water storage [48 hours] and thermocycling [2000 cycles]).
      Each group was divided into two subgroups (each, n=15): new - water storage at 37
      degrees C for one week; old - water storage for six months. The SBS was tested.
      The fracture mode was assessed under 40* magnification. RESULTS: Mean SBS values
      (MPa) for the study subgroups were as follows: control (new: 3.38 +/- 1.6; old: 1
      +/- 0.76), group 1 (new: 27.3 +/- 1.8; old: 25.7 +/- 1.9), group 2 (new: 59.1 +/-
      7.9; old: 50.8 +/- 4.6), and group 3 (new: 48.5 +/- 8.6; old: 39 +/- 3.5).
      Significant influence of the conditioning method and the duration of water
      storage was observed (p<0.01 [two-way analysis of variance {ANOVA}]). The SBS of
      all groups were significantly different (all p values <0.01 [Tukey]). Longer
      water storage time significantly reduced repair bond strength in all experimental
      groups (p<0.01). Although the control group and group 1 showed approximately 100%
      and 75% adhesive failures, respectively, groups 2 and 3, respectively,
      demonstrated about 75% mixed and cohesive failures. Weibull analysis showed that
      groups 2 and 1 had the lowest and highest probabilities of failure among the
      experimental groups, respectively. CONCLUSION: All experimental groups produced
      acceptable SBS levels; however, use of silane and bonding systems showed the most
      superior results. Acid etching reduced the SBS.

PMID- 21859314
TI  - Effect of ozone application on the resin-dentin microtensile bond strength.
AB  - When ozone is used during caries treatment, bond strength can be compromised by
      the release of oxygen. The use of antioxidant agents neutralizes the free oxygen.
      The aim of this study was to evaluate the effects of ozone and sodium ascorbate
      on resin-dentin microtensile bond strength (MUTBS). Forty human third molars were
      divided into four groups: Group 1, not treated with ozone; Group 2, ozone
      application followed by acid etching; Group 3, acid etching followed by ozone
      application; and Group 4, ozone and application of sodium ascorbate. Bonded beams
      (1.0 mm(2)) were tested under tension (0.5 mm min(-1)). The MUTBS values were
      analyzed using one-way analysis of variance (ANOVA) and the Tukey test (p=0.05).
      All beams that fractured were analyzed under stereomicroscopy (40*). Group 1 had
      significantly higher MUTBS values than Group 2 or 3. The MUTBS values of Groups 1
      and 4 were similar and higher than those of Group 2. The use of ozone in Group 2
      resulted in lower values of MUTBS in all conditions evaluated. The predominant
      failure mode was adhesive. The application of ozone decreased the MUTBS of the
      dentin-composite resin interface. These values were reversed when compared with
      Groups 1 and 2 when sodium ascorbate was used.

PMID- 21859315
TI  - Adhesion of resin composite to hydrofluoric acid-exposed enamel and dentin in
      repair protocols.
AB  - Intraoral repairs of ceramic fixed-dental-prostheses (FDP) often include cervical
      recessions that require pretreatment of the exposed tooth surfaces either before
      or after the ceramic is conditioned with hydrofluoric (HF) acid gel. The sequence
      of repair protocol may cross-contaminate the exposed etched enamel or dentin
      surfaces during the application or rinsing process and thereby affect the
      adhesion. This study evaluated the influence of HF acid gel with two
      concentrations on bond strengths of composite to enamel and dentin. Human third
      molars (N=100, n=10 per group) with similar sizes were selected and randomly
      divided into 10 groups. Flat surfaces of enamel and dentin were created by wet
      ground finishing. Before or after the enamel (E) or dentin (D) was conditioned
      with phosphoric acid (P), substrate surfaces were conditioned with either 9.5% HF
      (HF(9.5)) or 5% HF (HF(5)). Subsequently, a bonding agent (B) was applied. The
      experimental groups by conditioning sequence were as follows where the first
      letter of the group abbreviation represents the substrate (E or D) followed by
      the acid type and concentration: group 1 (EPHF(9.5)), group 2 (EPHF(5)), group 3
      (EHF(9.5)P), group 4 (EHF(5)P), group 5 (DPHF(9.5)), group 6 (DPHF(5)), group 7
      (DHF(9.5)P), and group 8 (DHF(5)P). Group 9 (EPB) and group 10 (DPB) acted as the
      control groups. Repair resin was adhered incrementally onto the conditioned
      enamel and dentin in polyethylene molds. Each layer was photo-polymerized for 40
      seconds. All specimens were thermocycled (*1000, 5 degrees -55 degrees C) and
      subjected to shear test (universal testing machine, 1 mm/min). Specimens that
      debonded during thermocycling were considered as 0 MPa. The bond strength data
      were analyzed using Kruskal-Wallis test and failure types using the chi-square
      test (alpha=0.05). Overall, the bond results (MPa) were lower on dentin than on
      enamel (p<0.01). EPB (25.6 +/- 6.6) and DPB (20.2 +/- 4.9) control groups showed
      significantly higher results than those of other groups (p<0.05). While higher
      mean bond strengths were obtained in group 1 (EPHF(9.5)) (11.5 +/- 2.1) and group
      2 (EPHF(5)) (7.3 +/- 0.6), lower results were obtained when HF acid gels were
      applied prior to phosphoric acid (EHF(9.5)P: 5.0 +/- 1.1, EHF(5)P: 3.6 +/- 0.1)
      (p<0.05). On dentin, the results were the lowest in group 8 (DHF(5)P: 1.5 +/-
      1.6), being significantly lower than those of group 5 (DPHF(9.5)) (p<0.05).
      Scanning electron microscope (SEM) images revealed predominantly mixed failures
      with less than half of the composite left on both enamel and dentin surfaces (64
      out of 80) (p<0.05), indicating that in general, adhesion was not ideal.
      Contamination of the enamel or dentin surfaces with HF acid gel impairs the bond
      strength of composites. Considering both the bond strength results and failure
      types, when dental tissues are to be repaired next to ceramic, application of
      phosphoric acid before HF acid gel application can be recommended. HF acid gel
      concentration did not influence the results except on enamel.

PMID- 21859316
TI  - Depth and distance perception of dentists and dental students.
AB  - The quality of work carried out by dentists is dependent, among other things, on
      experience, training, and manual dexterity. Historical focus on the latter as a
      predictor of dental performance has failed to recognize that dental competence
      also requires good perceptual and visual skills, not only for gathering
      information but also for judging positions, distances, and the size of objects
      and shapes. Most predictive tests ignore visual and interpretative deficiencies
      that could make individual acquisition of skills and interpretation of
      instructions difficult. Ability to estimate depth and distance, the manner in
      which students learn this ability, whether and how it can be taught, or whether
      there is an association among ability, stereopsis, and dental performance has not
      been thoroughly examined; nor has the perception that dental students fully
      understand verbal and written instruction relating to depth and distance. This
      study investigated the ability of dentists and dental students to estimate and
      reproduce small depths and distances and the relationship of this ability to
      stereopsis, dental experience, and student performance. A total of 163
      undergraduate dental students from three year groups and 20 experienced dentists
      and specialists performed three tasks. A depth-perception task involved
      estimation of the depth of two sets (2-mm or 4-mm wide) of nine computer milled
      slots ranging in depth from 0.5 to 4.0 mm. A distance task involved estimation of
      the width of specially prepared printed square blocks. In a writing task,
      participants recorded distances across a printed line on separate sheets of
      paper. All tasks were conducted at set positions in custom-made transportable
      light boxes. Stereopsis and visual acuity were also measured. Ability to perform
      perceptual tasks varied enormously, with the level of accuracy dependent on the
      type of task and dental experience. Many students had considerable difficulty in
      estimating depth. Inexperienced students performed poorly. Most participants
      overestimated depth and distance estimation tasks, but underestimated when
      required to draw distances. Smaller depths and distances were easier to estimate
      than larger ones. All groups overestimated depth more in 4-mm-wide blocks than in
      2-mm-wide blocks. There was no correlation found between depth and distance
      estimation and stereopsis scores or with the overall grades tested. This study
      highlights that some dentists and many dental students, particularly early in
      their course, have great difficulty in accurately gauging depths and distances.
      It is proposed that that this could impact significantly on a student's ability
      to interpret verbal and written preclinical instruction and could make the
      acquisition of manual skills and interpretation of clinical instruction
      difficult. Routine testing of all undergraduate dental students for perceptual
      and visual difficulties is recommended, so that those with difficulties can be
      identified and problems remedied, if possible, early in their course.

PMID- 21859317
TI  - Factors affecting the detection and treatment of occlusal caries using the
      International Caries Detection and Assessment System.
AB  - OBJECTIVE: To assess the variability in diagnosis and treatment of occlusal
      caries among dental practitioners in Kuwait using the International Caries
      Detection and Assessment System (ICDAS) criteria. METHODS: A representative
      random sample of 156 dentists were interviewed. After completing a survey that
      included information about their gender, age, years in practice, place of
      practice, place of dental education, and specialty, practitioners examined four
      separately mounted molars (I-IV) for probable occlusal caries according to the
      ICDAS-II visual criteria. They were then asked to answer a set of questions
      related to their diagnosis and treatment of each tooth. The teeth were then
      histologically sectioned, and two independent investigators evaluated the depth
      of the caries according to Hintze and Wenzel's histologic criteria. RESULTS:
      According to the histologic examination, tooth I and III had caries into enamel,
      while tooth II and IV had caries into dentin. About 50% of the participants
      diagnosed teeth with enamel caries as sound. About 60% of the participants
      correctly diagnosed teeth with caries extending into dentin. A restorative
      treatment modality was recommended for enamel caries by approximately 50% of the
      participants and for dentin caries by more than 80% of the participants. Dentists
      with a specialty in restorative dentistry had a tendency to underdiagnose enamel
      caries, while general practitioners and other specialists tended to overtreat
      enamel caries. CONCLUSIONS: There was an evident variability in the diagnosis and
      treatment choices of occlusal caries among dentists working in Kuwait. Among the
      factors studied, the specialty of the participants was the only factor that had
      an effect on the participants' diagnosis and treatment of occlusal caries.

PMID- 21859319
TI  - Destructive membranous periodontal disease (ligneous gingivitis): a literature
      review.
AB  - BACKGROUND: Destructive membranous periodontal disease, or ligneous gingivitis,
      is a rare condition involving nodular gingival enlargement with ulceration and
      periodontal tissue destruction. This review gives a brief account of the cases
      reported in the literature. An effort is also made to define the periodontal
      disease caused by plasminogen deficiency with a view to its potential inclusion
      in the classification of periodontal diseases. METHODS: A MEDLINE/PubMed and
      manual search was conducted to find papers describing >=1 case of ligneous
      disease involving the oral mucosa. RESULTS: We identified 23 articles reporting
      35 cases. For each patient, we analyzed various characteristics, including age,
      sex, age of onset, oral symptoms, histologic features, plasminogen levels
      (functional activity, plasma antigen), genetic features, treatment, and results
      of treatment during the reported follow-up. CONCLUSIONS: Ligneous gingivitis is a
      rare periodontal disorder closely associated with ligneous conjunctivitis and
      plasminogen deficiency. Its diagnosis may be supported by the finding of genetic
      mutations responsible for the condition. Research is focusing on the future
      development of an effective therapy capable of arresting the destructive
      evolution of the disease. Additional studies, investigating features such as
      probing depth and attachment loss, are needed for the appropriate classification
      of this periodontal disease.

PMID- 21859318
TI  - A clinical study comparing the efficacy and sensitivity of home vs combined
      whitening.
AB  - This randomized clinical study assessed efficacy in terms of color change and
      production of sensitivity after home whitening alone and home whitening
      supplemented with in-office bleaching. Thirty-six subjects (aged 19 to 58 years)
      were randomly assigned to one of three different treatment groups: (A) home
      whitening for two weeks, with 16% carbamide peroxide in custom-made trays; (B)
      home whitening for two weeks, with 16% carbamide peroxide in custom-made trays
      supplemented with in-office bleaching with 9% hydrogen peroxide (in the same
      trays); or (C) home whitening for two weeks, with 16% carbamide peroxide in
      custom-made trays supplemented with in-office bleaching with 27% hydrogen
      peroxide (in the same trays). The efficacy of tooth whitening was assessed by
      determining the color change associated with the six upper anterior teeth using a
      value-ordered shade guide. Sensitivity was self-assessed with the use of a visual
      analog scale (VAS). Tooth shade and sensitivity were assessed at the following
      points: pretreatment; immediately after the home whitening phase; immediately
      after the in-office phase (groups B and C); and one week post active treatment.
      At the one week follow-up visit, subjects in group A had a mean (SD) color change
      of 5.9 (1.83) (teeth were lighter) immediately after cessation of treatment
      (p<0.01). Subjects in groups B and C experienced a greater change in mean (SD)
      shade immediately following their respective in-office treatments of 5.1 (1.53)
      and 5.4 (1.55). However, within one week, the shade of these teeth regressed to a
      similar degree to that achieved by subjects treated in group A. Overall, no
      significant difference in shade change or sensitivity was produced between the
      three groups. Investigators concluded that the in-office element of combined
      whitening produced no significant difference in tooth color or sensitivity when
      compared with home whitening alone.

PMID- 21859320
TI  - Validity of partial protocols to assess the prevalence of periodontal outcomes
      and associated sociodemographic and behavior factors in adolescents and young
      adults.
AB  - BACKGROUND: Most studies comparing prevalence of periodontal disease and risk
      factors by using partial protocols were performed in adult populations, with
      several studies being conducted in clinical settings. The aim of this study is to
      assess the accuracy of partial protocols in estimating the prevalence of
      periodontal outcomes in adolescents and young adults from two population-based
      birth cohorts from Pelotas, Brazil, and to assess differences in the estimation
      and strength of the effect measures when partial protocols are adopted compared
      to full-mouth examination. METHODS: Gingival bleeding at probing among
      adolescents (n = 339) and young adults (n = 720) and dental calculus and
      periodontal probing depth among young adults were assessed using full-mouth
      examinations and four partial protocols: Ramfjord teeth (RT), community
      periodontal index (CPI), and two random diagonal quadrants (1 and 3, 2 and 4).
      Socioeconomic, demographic, and periodontal health-related variables were also
      collected. Sensitivity, absolute and relative bias, and inflation factors were
      calculated. Prevalence ratio for each periodontal outcome for the risk factors
      was estimated. RESULTS: Two diagonal quadrants showed better accuracy; RT had the
      worst, whereas CPI presented an intermediate pattern when compared to full-mouth
      examination. For bleeding assessment in adolescence, RT and CPI underestimated by
      18.4% and 16.2%, respectively, the true outcome prevalence, whereas among young
      adults, all partial protocols underestimated the prevalence. All partial
      protocols presented similar magnitude of association measures for all
      investigated periodontal potential risk factors. CONCLUSION: Two diagonal
      quadrants protocol may be effective in identifying the risk factors for the most
      relevant periodontal outcomes in adolescence and in young adulthood.

PMID- 21859321
TI  - Interleukin-33 levels in gingival crevicular fluid, saliva, or plasma do not
      differentiate chronic periodontitis.
AB  - BACKGROUND: This study investigates whether gingival crevicular fluid (GCF),
      saliva, and plasma levels of interleukin-33 (IL-33) can differentiate individuals
      with chronic periodontitis from individuals with healthy periodontium. METHODS:
      GCF, whole saliva, and plasma samples together with full-mouth clinical
      periodontal recordings were obtained from 32 otherwise healthy, non-smoker
      chronic periodontitis individuals and 25 systemically and periodontally healthy,
      non-smoker individuals. IL-33 levels in the biofluid samples were determined by
      enzyme-linked immunosorbent assay. Data were tested statistically by Mann-Whitney
      U test. RESULTS: The GCF concentrations of IL-33 were significantly lower in
      chronic periodontitis individuals than in healthy individuals (P <0.0001),
      whereas the total amounts in GCF samples were similar (P >0.05). The salivary and
      plasma contrations of IL-33 were indifferent in the two study groups (P >0.05).
      CONCLUSIONS: According to the present findings, the GCF, saliva or plasma levels
      of IL-33 could not differentiate chronic periodontitis individuals and
      periodontally healthy individuals. Larger-scale intervention studies may better
      clarify this issue.

PMID- 21859322
TI  - Expression of immune-inflammatory markers in sites of chronic periodontitis in
      patients with type 2 diabetes.
AB  - BACKGROUND: The aim of this study is to evaluate the gene expression of immune
      inflammatory markers in gingival biopsies of patients with type 2 diabetes with
      chronic periodontitis (CP). METHODS: Gingival biopsies were harvested from
      systemically and periodontally healthy patients (SPH), systemically healthy
      patients with CP (SHCP), and patients with better-controlled and poorly
      controlled diabetes and CP. The levels of mRNA of interleukin (IL)-17, IL-6, IL
      23, IL-10, IL-4, interferon-gamma, toll-like receptor (TLR)-2, TLR-4,
      osteoprotegerin, receptor activator of nuclear factor-kappa B ligand (RANKL),
      tumor necrosis factor-alpha, transforming growth factor-beta, transcription
      factor forkhead box p3, transcription factor orphan nuclear receptor C2 (RORC2),
      and receptor of advanced glycation end products (RAGE) were evaluated by
      quantitative real-time polymerase chain reaction. RESULTS: All CP groups
      presented higher levels of mRNA of TLR-2, TLR-4, IL-17, RANKL, and RAGE and a
      higher frequency of IL-17 and TLR-2 mRNA-positive biopsies when compared to SPH
      (P <0.05). There was a higher frequency of detection of RORC2 in the biopsies
      from both groups with diabetes compared to the other groups (P <0.05). The
      frequency of IL-4 mRNA-positive tissues was lower in patients with diabetes
      compared to SHCP (P <0.05). CONCLUSION: CP, but not type 2 diabetes mellitus,
      significantly affected the expressions of the evaluated genes related to the
      innate and adaptive immune responses.

PMID- 21859323
TI  - Effects of non-surgical periodontal treatment on clinical response, serum
      inflammatory parameters, and metabolic control in patients with type 2 diabetes:
      a randomized study.
AB  - BACKGROUND: Scientific evidence on the effects of chronic periodontitis on
      diabetes mellitus remains inadequate and inconclusive. This intervention study is
      designed to evaluate the effects of periodontal treatment on clinical response,
      systemic inflammatory parameters, and metabolic control in patients with Type 2
      diabetes. METHODS: A total of 134 patients were randomly allocated into two
      treatment groups and one control group. Treatment group 1 underwent non-surgical
      periodontal treatment at baseline and additional subgingival debridement at the 3
      month follow-up. Patients in treatment group 2 received non-surgical periodontal
      treatment and supragingival prophylaxis at the 3-month follow-up, and those in
      the control group received no intervention throughout the study. All participants
      were reexamined at 1.5, 3, and 6 months after initial treatment. At each visit,
      clinical periodontal examinations were conducted and blood samples were taken to
      evaluate high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha
      (TNF-alpha), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and lipid
      profiles. RESULTS: Both treatment groups had a significantly lower hsCRP level
      after periodontal therapy (P <0.05). Although HbA1c declined significantly in
      treatment group 2 (P <0.05), the intergroup difference for HbA1c, FPG, TNF-alpha,
      and lipid profiles was not statistically significant after therapy (P >0.05).
      CONCLUSIONS: Non-surgical periodontal treatment can effectively improve
      periodontal and circulating inflammatory status. Despite a lack of strong
      evidence, trends in some results support improved glycemic control after
      periodontal treatment in patients with diabetes.

PMID- 21859325
TI  - Variation in lunar neutron dose estimates.
AB  - The radiation environment on the Moon includes albedo neutrons produced by
      primary particles interacting with the lunar surface. In this work, HZETRN2010 is
      used to calculate the albedo neutron contribution to effective dose as a function
      of shielding thickness for four different space radiation environments and to
      determine to what extent various factors affect such estimates. First, albedo
      neutron spectra computed with HZETRN2010 are compared to Monte Carlo results in
      various radiation environments. Next, the impact of lunar regolith composition on
      the albedo neutron spectrum is examined, and the variation on effective dose
      caused by neutron fluence-to-effective dose conversion coefficients is studied. A
      methodology for computing effective dose in detailed human phantoms using
      HZETRN2010 is also discussed and compared. Finally, the combined variation caused
      by environmental models, shielding materials, shielding thickness, regolith
      composition and conversion coefficients on the albedo neutron contribution to
      effective dose is determined. It is shown that a single percentage number for
      characterizing the albedo neutron contribution to effective dose can be
      misleading. In general, the albedo neutron contribution to effective dose is
      found to vary between 1-32%, with the environmental model, shielding material and
      shielding thickness being the driving factors that determine the exact
      contribution. It is also shown that polyethylene or other hydrogen-rich materials
      may be used to mitigate the albedo neutron exposure.

PMID- 21859324
TI  - Evidence-based periodontal plastic surgery. II. An individual data meta-analysis
      for evaluating factors in achieving complete root coverage.
AB  - BACKGROUND: The aim of this review is to conduct an individual patient data meta
      analysis of randomized controlled clinical trials (RCTs) to evaluate whether
      baseline recession-, patient-, and procedure-related factors can influence the
      achievement of complete root coverage (CRC). METHODS: A literature search with no
      restrictions regarding status or the language of publication was performed for
      MEDLINE (for Medical Literature Analysis and Retrieval System Online), EMBASE
      (for Excerpta Medica Database), CENTRAL (for Cochrane Central Register of
      Controlled Trials), and the Cochrane Oral Health Group's Specialized Register
      databases up to and including March 2011. Only RCTs, with a duration of >=6
      months evaluating recession areas (Miller Class I or II) that were treated by
      means of root coverage procedures were included. Mixed-effects logistic
      regression analyses were conducted to evaluate associations between five baseline
      variables and CRC. RESULTS: Of the 70 potentially eligible trials, 22 were
      included in the meta-analyses. In total, the data from 320 patients and 16
      procedures were evaluated. None of the RCTs were classified as low risk of bias.
      Of the 602 recessions treated, 310 (51.5%) achieved CRC. Subepithelial connective
      tissue grafts (SCTGs), matrix grafts, and enamel matrix derivative protein (EMD)
      procedures were superior in achieving CRC when compared to coronally advanced
      flap (CAF) alone. For the adjusted covariates, the greater the baseline recession
      depth, the smaller the chance of achieving CRC (individual procedure analysis
      [odds ratio (OR) = 0.55; 95% confidence interval (CI) = 0.44, 0.70] and grouped
      procedure analysis [OR = 0.56; 95% CI = 0.45, 0.71]), as well as studies with
      conflict of interest were more likely to achieve CRC than those without conflict
      of interest (individual procedure analysis [OR = 6.78; 95% CI = 1.78, 25.86]).
      CONCLUSIONS: SCTGs, matrix grafts, and EMD were superior to CAF in achieving CRC,
      but SCTGs showed the best predictability. The impossibility of inclusion of all
      identified RCTs should be taken into consideration when interpreting the present
      findings.

PMID- 21859326
TI  - Acute biological effects of simulating the whole-body radiation dose distribution
      from a solar particle event using a porcine model.
AB  - In a solar particle event (SPE), an unshielded astronaut would receive proton
      radiation with an energy profile that produces a highly inhomogeneous dose
      distribution (skin receiving a greater dose than internal organs). The novel
      concept of using megavoltage electron-beam radiation to more accurately reproduce
      both the total dose and the dose distribution of SPE protons and make meaningful
      RBE comparisons between protons and conventional radiation has been described
      previously. Here, Yucatan minipigs were used to determine the effects of a
      superficial, SPE-like proton dose distribution using megavoltage electrons. In
      these experiments, dose-dependent increases in skin pigmentation, ulceration,
      keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals
      (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy
      radiation) developed symptomatic, radiation-associated pneumonopathy
      approximately 90 days postirradiation. The three animals from the highest dose
      group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis.
      Moreover, delayed-type hypersensitivity was found to be altered, suggesting that
      superficial irradiation of the skin with ionizing radiation might cause immune
      dysfunction or dysregulation. In conclusion, using total doses, patterns of dose
      distribution, and dose rates that are compatible with potential astronaut
      exposure to SPE radiation, animals experienced significant toxicities that were
      qualitatively different from toxicities previously reported in pigs for
      homogeneously delivered radiation at similar doses.

PMID- 21859328
TI  - Acyclovir is a substrate for the human breast cancer resistance protein
      (BCRP/ABCG2): implications for renal tubular transport and acyclovir-induced
      nephrotoxicity.
AB  - The human breast cancer resistance protein (BCRP/ABCG2) is widely expressed in
      human tissues, including the kidney. In mice, Bcrp1 (murine BCRP ortholog)
      mediates the transport of acyclovir into breast milk. It is plausible that
      acyclovir is also a substrate for the human BCRP. The objective of the study was
      to determine whether acyclovir is a substrate for human BCRP. Transfected human
      embryonic kidney (HEK293) cells (containing the wild-type ABCG2 gene) were
      exposed to [8-(14)C]acyclovir (1 umol/L) in the presence or absence of the BCRP
      inhibitor fumitremorgin C (FTC). Intracellular acyclovir accumulation was
      assessed using a liquid scintillation counter. Coexposure to FTC resulted in a
      significant (5-fold) increase in the intracellular accumulation of acyclovir. The
      results suggest that acyclovir is a substrate for human BCRP. The study is the
      first to provide direct evidence for the role of human BCRP in acyclovir
      transport and its potential significance with respect to renal tubular transport
      of acyclovir and the direct renal tubular insult induced by the drug.

PMID- 21859327
TI  - Rapid loss of bone mass and strength in mice after abdominal irradiation.
AB  - Localized irradiation is a common treatment modality for malignancies in the
      pelvic-abdominal cavity. We report here on the changes in bone mass and strength
      in mice 7-14 days after abdominal irradiation. Male C57BL/6 mice of 10-12 weeks
      of age were given a single-dose (0, 5, 10, 15 or 20 Gy) or fractionated (3 Gy * 2
      per day * 7.5 days) X rays to the abdomen and monitored daily for up to 14 days.
      A decrease in the serum bone formation marker and ex vivo osteoblast
      differentiation was detected 7 days after a single dose of radiation, with little
      change in the serum bone resorption marker and ex vivo osteoclast formation. A
      single dose of radiation elicited a loss of bone mineral density (BMD) within 14
      days of irradiation. The BMD loss was up to 4.1% in the whole skeleton, 7.3% in
      tibia, and 7.7% in the femur. Fractionated abdominal irradiation induced similar
      extents of BMD loss 10 days after the last fraction: 6.2% in the whole skeleton,
      5.1% in tibia, and 13.8% in the femur. The loss of BMD was dependent on radiation
      dose and was more profound in the trabecula-rich regions of the long bones.
      Moreover, BMD loss in the total skeleton and the femurs progressed with time.
      Peak load and stiffness in the mid-shaft tibia from irradiated mice were 11.2
      14.2% and 11.5-25.0% lower, respectively, than sham controls tested 7 days after
      a single-dose abdominal irradiation. Our data demonstrate that abdominal
      irradiation induces a rapid loss of BMD in the mouse skeleton. These effects are
      bone type- and region-specific but are independent of radiation fractionation.
      The radiation-induced abscopal damage to the skeleton is manifested by the
      deterioration of biomechanical properties of the affected bone.

PMID- 21859329
TI  - Impairment of endothelial protection by ischemic postconditioning in patients
      with major depressive disorder.
AB  - This study used a model of ischemia-reperfusion injury to the brachial artery
      endothelium to investigate whether the protective role of ischemic
      postconditioning (IPostC) is impaired in patients with major depressive episode.
      Flow-mediated dilation (FMD) was measured before and after ischemia-reperfusion
      in the absence or presence of IPostC in 24 patients with major depressive
      disorder and 20 healthy controls. In addition, the severity of the depression, as
      assessed by the Hamilton Depression Rating Scale (HDRS) and Beck Depression
      Inventory (BDI) scores, and plasma nitrogen dioxide (NO(x)) levels were also
      determined. Ischemia-reperfusion resulted in a significant decrease in FMD in
      both patients with a major depressive episode and healthy controls. IPostC
      effectively prevented this decrease in FMD in healthy controls, but not in
      patients with a major depressive episode. HDRS and BDI scores were markedly
      increased, but plasma NO(x) levels decreased, in patients with a major depressive
      episode compared with those in healthy controls. Correlation analysis showed that
      HDRS and BDI scores and plasma NO(x) levels were significantly associated with
      post-ischemia-reperfusion FMD. These results suggest that endothelial protection
      by IPostC is impaired in patients with major depressive disorder, which may be
      related to the decrease in endothelial nitric oxide production and the severity
      of the depression.

PMID- 21859331
TI  - Grouping patients for masseter muscle genotype-phenotype studies.
AB  - OBJECTIVES: To use various facial classifications, including either/both vertical
      and horizontal facial criteria, to assess their effects on the interpretation of
      masseter muscle (MM) gene expression. MATERIALS AND METHODS: Fresh MM biopsies
      were obtained from 29 patients (age, 16-36 years) with various facial phenotypes.
      Based on clinical and cephalometric analysis, patients were grouped using three
      different classifications: (1) basic vertical, (2) basic horizontal, and (3)
      combined vertical and horizontal. Gene expression levels of the myosin heavy
      chain genes MYH1, MYH2, MYH3, MYH6, MYH7, and MYH8 were recorded using
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and were
      related to the various classifications. The significance level for statistical
      analysis was set at P <= .05. RESULTS: Using classification 1, none of the MYH
      genes were found to be significantly different between long face (LF) patients
      and the average vertical group. Using classification 2, MYH3, MYH6, and MYH7
      genes were found to be significantly upregulated in retrognathic patients
      compared with prognathic and average horizontal groups. Using classification 3,
      only the MYH7 gene was found to be significantly upregulated in retrognathic LF
      compared with prognathic LF, prognathic average vertical faces, and average
      vertical and horizontal groups. CONCLUSION: The use of basic vertical or basic
      horizontal facial classifications may not be sufficient for genetics-based
      studies of facial phenotypes. Prognathic and retrognathic facial phenotypes have
      different MM gene expressions; therefore, it is not recommended to combine them
      into one single group, even though they may have a similar vertical facial
      phenotype.

PMID- 21859330
TI  - Seroprevalence of Toxoplasma gondii in dogs in Shandong, Henan, and Heilongjiang
      Provinces, and in the Xinjiang Uygur Autonomous Region, People's Republic of
      China.
AB  - Seroprevalence of Toxoplasma gondii infection was determined in sera of 632 dogs
      (551 pets, 81 strays) from Shandong, Henan, and Heilongjiang Provinces, and in
      the Xinjiang Uygur Autonomous Region, People's Republic of China (PRC), using the
      indirect hemagglutination assay (cutoff titer 1:64 or higher); 11.1% were
      seropositive. The seroprevalence in stray dogs and in >=3-yr-old dogs was
      significantly higher (P < 0.05) than that in household dogs and in <3-yr-old
      dogs. There were no significant differences in terms of gender, breed, or
      locality (P >= 0.05). The results indicate that T. gondii infections are common
      in dogs in PRC.

PMID- 21859332
TI  - Multiple miliary osteoma cutis: treatment with CO(2) laser and hook.
AB  - Miliary osteoma cutis refers to the variant of morphologically normal bone
      formation disorder in the dermis or subcutaneous tissue. The etiology of miliary
      osteoma cutis is still uncertain. But it may be due to osteoblastic metaplasia of
      mesenchymal elements. In our case, a healthy 55-year-old woman presented with
      multiple, skin-colored, non-tender, firm papules measuring 1 to 3 mm in diameter
      disseminated over the both cheeks for 3 years. We treated her with carbon dioxide
      (CO(2)) laser extraction with the hook through a small hole and patient had
      dramatic response to quick and simple treatment modality.

PMID- 21859333
TI  - Relation between antibiotic susceptibility and ultrastructure of Staphylococcus
      aureus biofilms on surgical suture.
AB  - BACKGROUND: Infectious biofilms are recalcitrant to antimicrobial therapy, but
      the mechanism(s) responsible for the greater resistance are unclear. Experiments
      were designed to clarify the association between antibiotic resistance and
      biofilm ultrastructure. METHODS: Staphylococcus aureus was cultivated for 24 h on
      silk suture, where robust biofilms formed. Initial experiments compared the
      susceptibilities of planktonic (free-living) cells and mechanically dispersed
      biofilm cells to ampicillin, oxacillin, and vancomycin. Antibiotics in
      bactericidal concentrations were then incubated overnight with 24-h biofilms, and
      subsequent assays determined the viability of cells in mechanically dispersed
      biofilms, biofilm metabolic capacity and biomass, and biofilm ultrastructure
      (scanning electron microscopy). RESULTS: Planktonic and biofilm cells had similar
      intrinsic antibiotic susceptibility. Nonetheless, a stable population of bacteria
      remained viable after biofilms were incubated with inhibitory drug
      concentrations, although biofilm metabolic capacity often was not detected, and
      biomass generally was reduced. Electron microscopy revealed that control (no
      drug) biofilms consisted primarily of bacterial clusters amid fibrillar elements.
      Antibiotic-treated biofilms had some staphylococci with smooth cells walls
      similar to planktonic cells, but other cocci were encased in extracellular
      material. This material was more abundant in antibiotic-treated than in control
      biofilms. CONCLUSIONS: In the presence of high antibiotic concentrations, dense
      extracellular material may inhibit interaction of antibiotics with their
      bacterial targets.

PMID- 21859335
TI  - Surgical outcome of community-acquired Clostridium difficile colitis presenting
      as toxic megacolon: case report.
AB  - BACKGROUND: Over the past decade, there has been an increase in both community
      acquired and health-care-associated Clostridium difficile colitis secondary to
      broad-spectrum antibiotic exposure. Toxic megacolon is a rare complication of
      pseudomembranous colitis that often necessitates emergency colectomy. METHODS:
      Review of the pertinent English-language literature. RESULTS: We present a case
      of community-acquired C. difficile colitis that made its initial presentation as
      fulminant toxic megacolon. Six months after a total colectomy, the patient has no
      complaints. CONCLUSION: Prompt total colectomy may improve survival in patients
      with toxic megacolon. The incidence of C. difficile-related toxic megacolon and
      post-operative outcomes of total colectomy should be investigated in a larger
      observational study.

PMID- 21859334
TI  - Patient outcomes associated with 2-octyl cyanoacrylate topical skin adhesive in
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Surgical site infection (SSI) is an important cause of morbidity and
      occasionally death after coronary artery bypass graft (CABG) surgery. These
      infections also are associated with higher costs and poorer surgical outcomes. We
      used a retrospective observational database to examine and quantify the effects
      of the topical skin adhesive 2-octyl cyanoacrylate, used as the final layer of
      site closure in patients undergoing CABG surgery, on the incidence of post
      operative SSI. METHODS: All patients in the Premier PerspectiveTM Comparative
      Database of inpatient hospitalizations who underwent CABG surgery in 2005 and
      2006 were identified. Qualifying patients were classified into four groups
      according to the method of surgical site closure on the basis of detailed
      hospital billing charges: Sutures only; sutures and 2-octyl cyanoacrylate;
      sutures and staples; and sutures, 2-octyl cyanoacrylate, and staples. Site
      infections were identified by a combination of International Classification of
      Diseases (ICD-9-CM) diagnosis codes, patterns of post-operative use of
      antibiotics, and All Patient Refined Diagnostic Related Group (APR-DRG) and
      Diagnostic Related Group (DRG) codes indicating post-operative infections at
      hospital re-admission. RESULTS: A total of 59,006 patients qualified for the
      study: 38,799 who had sutures only; 10,262 having sutures and 2-octyl
      cyanoacrylate; 8,180 having sutures and staples; and 1,765 having sutures, 2
      octyl cyanoacrylate, and staples. The lowest unadjusted rate of post-CABG SSI was
      found in the sutures and 2-octyl cyanoacrylate group (4.3%; 95% confidence
      interval [CI] 3.9-4.7), followed by sutures only (5.3%; 95% CI 5.1-5.5); sutures
      and staples (6.2%; 95% CI 5.7-6.8); and sutures, staples, and 2-octyl
      cyanoacrylate (7.1%; 95% CI 6.0%-8.4%). A logistic regression model that
      controlled for selected baseline patient, hospital, and surgical characteristics
      showed significantly lower rates of post-CABG SSI (odds ratio 0.76; 95% CI 0.68
      0.85) in patients closed with sutures and 2-octyl cyanoacrylate relative to
      patients who had only sutures. CONCLUSIONS: The observed rates of post-CABG SSI
      were consistent with the rates observed in the literature. The SSI rate for
      patients who had sutures and 2-octyl cyanoacrylate used as the final layer of
      site closure was significantly lower than the rates for patients having other
      types of closure.

PMID- 21859336
TI  - Periappendiceal submucosal abscess presenting as a cecal mass.
AB  - BACKGROUND: Submucosal abscesses are rare in the gastrointestinal tract. Although
      they have been reported throughout the tract, occurrence within the appendix has
      not been described. METHODS: Case report and review of the current literature.
      RESULTS: We present the case of a patient with a periappendiceal mass found
      incidentally on workup for anemia. An ileocecectomy was performed for presumed
      cecal neoplasm. Histologic examination showed a submucosal periappendiceal
      abscess with no evidence of malignancy. CONCLUSION: This case is unique because
      although appendiceal abscesses often occur as a result of acute appendicitis, our
      patient presented with an incidental periappendiceal submucosal abscess, not
      preceded by any gastrointestinal infection or surgery. Periappendiceal submucosal
      abscess should be included in the differential diagnosis of masses found on
      colonoscopy.

PMID- 21859337
TI  - Use of meropenem by continuous infusion to treat a patient with a Bla(kpc-2)
      positive Klebsiella pneumoniae blood stream infection.
AB  - BACKGROUND: Gram-negative bacterial resistance to antibiotics is of increasing
      concern. Carbapenem resistance among strains of Klebsiella pneumoniae is a
      relatively new phenomenon. Resistance attributable to production of
      carbapenemases is notoriously difficult to combat. METHODS: Case report and
      review of the pertinent English-language literature. RESULTS: A patient,
      hospitalized for aortic dissection complicated by intra-abdominal catastrophe and
      acute kidney injury, developed bacteremia exhibiting meropenem non-susceptibility
      secondary to expression of bla(KPC-2). High-dose, continuous-infusion meropenem
      achieved serum drug concentrations above the minimum inhibitory concentration and
      eradicated the infection. CONCLUSION: This is the first report of a meropenem-non
      susceptible carbapenamase-positive Klebsiella pneumoniae blood stream infection
      treated successfully with high-dose, continuous-infusion meropenem. Application
      of this regimen in certain patients, such as those with mild-to-moderate renal
      insufficiency, may be a reasonable option for multi-drug-resistant nosocomial
      infections.

PMID- 21859338
TI  - Combined Serratia liquefaciens and Mycobacterium tuberculosis in temporal
      osteitis with brain extension.

PMID- 21859339
TI  - Chronic spinal cord abscess in an elderly patient.
AB  - BACKGROUND: Spinal cord abscesses are rare. Acute lesions may present as spinal
      cord syndrome with back pain and fever, whereas chronic abscesses tend to have a
      less specific symptomatology, especially in elderly patients. METHODS: Case
      report and review of the pertinent literature. CASE REPORT: An 82-year old male
      with diabetes mellitus presented with a four-month history of backache and some
      difficulty walking without sphincter disturbance or fever. Spinal magnetic
      resonance imaging revealed a midthoracic intramedullary ring-like lesion that
      proved to be an abscess. Corticosteroids, gentamicin, and ciprofloxacin were
      given. The abscess resolved after three months. CONCLUSIONS: Classically,
      treatment of intramedullary abscesses involves surgical drainage of the abscess
      cavity and administration of appropriate antibiotics, although medical therapy
      alone may be appropriate in some cases. If the diagnosis is unclear or patients
      do not respond to medical management, surgical decompression should be performed.

PMID- 21859340
TI  - Robotic-assisted ureteral reimplantation with Boari flap and psoas hitch: a
      single-institution experience.
AB  - Robotic-assisted ureteral reimplantations were performed on 3 patients at a
      single institution, 2 with Boari flap and psoas hitch and 1 with psoas hitch
      alone. These were for urothelial carcinoma of the distal ureter, ureteral
      obstruction caused by distal ureteral endometriosis, and ureteral transaction
      during gynecologic surgery. We used intraoperative ureteroscopy to confirm tumor
      margins as well as a simple technique for retrograde placement of transvesicle
      wire prior to ureteral anastomosis. Surgery and recovery were uneventful. This
      illustrates that robotic-assisted ureteral reimplantation with Boari flap and
      psoas hitch is a safe and viable approach for ureterovesicle reconstruction.

PMID- 21859341
TI  - A pilot study of laparoscopic gastric pull-up by using the natural orifice
      translumenal endoscopic surgery technique: a novel procedure for treating long
      gap esophageal atresia (type a).
AB  - AIM: This study aimed to develop a novel procedure for treating long-gap pure
      esophageal atresia. This procedure, which entails the combined use of laparoscopy
      and natural orifice translumenal endoscopic surgery (NOTES), would enable primary
      repair without cervical and thoracic incisions and prevent postoperative
      gastroesophageal reflux disease (GERD). METHODS: Nonsurvival experiments were
      conducted in 9 pigs to study the technical feasibility. The procedure comprised
      the following: (1) creation of the disease model by laparoscopic resection of the
      lower esophagus; (2) laparoscopic fundoplication, complete mobilization of the
      stomach, and enlargement of the esophageal hiatus; (3) formation of a peroral
      transesophageal entry site into either the postmediastinum or the right thoracic
      cavity followed by fashioning a tunnel to the peritoneal cavity; (4) gastric pull
      up by using both laparoscopy and NOTES; (5) esophagoesophageal anastomosis using
      BraceBarTM, a prototype of the double T-bar suturing device (Olympus Medical
      Systems Co., Tokyo, Japan). RESULTS: Laparoscopic procedures were performed
      without complications. The postmediastinal tunnel was successfully created three
      times with a complication of pleural injury. However, gastric pull-up via this
      route could not be completed due to porcine anatomical reasons. Gastric pull-up
      through the right thoracic route was achieved five times in six attempts. Two
      disorientations and a hemorrhagic death occurred during the procedures.
      CONCLUSIONS: This study showed that combined use of laparoscopy and NOTES enabled
      gastric pull-up without cervical and thoracic incisions. Our method has the
      potential of lowering the incidence of GERD and enabling primary repair of this
      disease.

PMID- 21859342
TI  - The use of high-frequency oscillating ventilation to facilitate stability during
      neonatal thoracoscopic operations.
AB  - BACKGROUND: Thoracoscopy has become a surgical option for the repair of
      esophageal atresia (EA) and congenital diaphragmatic hernia (CDH). Insufflation
      of carbon dioxide combined with one lung ventilation creates an anesthetic
      challenge to control acidosis and maintain oxygenation while allowing optimal
      operative exposure. We have overcome these issues by utilizing the high-frequency
      oscillating ventilator (HFOV) and report our early experience. METHODS: A
      retrospective review from 2007 to 2010 on neonates who underwent thoracoscopic
      operation utilizing HFOV. Patient demographics and intraoperative course were
      reviewed. RESULTS: Seventeen neonates were identified, 12 with EA and 5 with
      posterolateral CDH. The median age at operation was 4 days (range 1-166 days),
      with a median weight of 2.9 +/- 1.0 kg. Median gestational age was 38 +/- 3
      weeks. Before surgery, 6 patients (35%) were on conventional mechanical
      ventilation, and no patient was on high-frequency oscillating ventilation. Median
      American Society of Anesthesiologist's score was 3 (range 3-4). There were no
      intraoperative complications and median operative time was 208 +/- 72 minutes.
      Review of the operative reports identified no significant difficulties with
      exposure of the operative field in all patients. Median ventilator manipulations
      needed were 3 per case. Mean intraoperative pulse oximetry was 97% +/- 2%.
      Sixteen patients had intraoperative arterial blood gases; 1 had venous sampling.
      Patients with arterial blood gases had a mean pH of 7.36 (range 7.18-7.47), mean
      pCO2 was 41 mmHg (range 25-63 mmHg), and mean pO2 was 156 mm Hg (range 41-426
      mmHg). CONCLUSION: Usage of HFOV allows for good intraoperative exposure with
      excellent oxygenation and elimination of carbon dioxide to prevent acidosis.

PMID- 21859343
TI  - Single-incision laparoscopic approach to management of splenic pathology in
      children: an early experience.
AB  - PURPOSE: Certain splenic conditions in children require surgical interventions,
      the majority of which are approached via standard laparoscopy with multiple
      incisions. The single-incision laparoscopic (SIL) technique is gaining
      popularity. The aim of this study is to review our institutional experience using
      the SIL technique to surgically manage different splenic pathology in the
      pediatric population. METHODS: A retrospective review was performed of the
      patients who underwent SIL splenic procedures at Miller Children's Hospital (Long
      Beach, CA) from January 2009 to December 2010. RESULTS: Seven patients underwent
      a SIL technique for different splenic diseases. Five patients underwent
      splenectomy, 1 patient underwent a splenic cystectomy and omental patching, and 1
      patient underwent reduction of splenic torsion and splenopexy. There were no
      conversions to open. Six procedures were successfully performed without the need
      for an additional trocar. However, 1 patient required an additional grasper
      through a separate stab incision. There were no intraoperative complications. One
      patient had a superficial wound infection at 2-week postoperative follow-up,
      which resolved with local wound care. CONCLUSIONS: Our preliminary experience
      shows the SIL technique for the management of splenic pathology in children is
      safe and feasible.

PMID- 21859345
TI  - Inhibition of adjuvant arthritis in rats by electroporation with interleukin-1
      receptor antagonist.
AB  - To assess the protective effects of the cytokine inhibitor interleukin-1 receptor
      antagonist (IL-1ra) on gene induction, an electroporation technique to treat
      adjuvant-induced arthritis (AIA) in rats was established, and its advantage was
      estimated in the present study. Electroporation with human IL-1ra was performed
      in Lewis rats before and after induction of AIA. Local inflammation was evaluated
      by monitoring hind paw swelling, whereas histological evaluations were performed
      using paraffin embedded sections of hind paw specimens stained with hematoxylin
      and eosin. In addition, serum IL-1? levels were analyzed using an enzyme-linked
      immunosorbent assay. Induction of IL-1ra by our electroporation method inhibited
      systematic body weight loss and enhancement of local inflammation after
      intradermal injection of heat-killed Mycobacterium tuberculosis. Notably, IL-1ra
      electroporation reduced paw swelling, inflammation, and bone erosion scores in
      embedded sections and serum IL-1? levels induced in AIA rats. The IL-1ra gene
      induction using the present electroporation technique inhibited local and
      systematic inflammation in AIA rats. These results indicate that this method may
      represent a novel pharmacotherapy strategy for arthritis.

PMID- 21859344
TI  - Type I interferon and systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease
      associated with multiple immunologic abnormalities. Prominent among these is
      upregulation of type I interferon (IFN)?a powerful immune adjuvant. IFN is, in
      part, produced in SLE in response to autoantigens in the form of self-nucleic
      acids and their associated nuclear proteins. Sources of these autoantigens
      include apoptotic and necrotic cells as well as neutrophils undergoing a specific
      form of cell death called NETosis. Although plasmacytoid dendritic cells are the
      main producers of IFN-a, other cells are important regulators of this process.
      Both genetic and environmental risk factors play a role in the development and
      pathogenesis of SLE. Further highlighting the importance of IFN, candidate gene
      and genome-wide association studies have identified a number of genes involved in
      type I IFN pathways associated with SLE. In this review, 3 monogenic deficiencies
      that result in lupus-like phenotypes and several polygenic variants that have
      been consistently associated with SLE are highlighted, and the relationship of
      these genes to IFN-a production is discussed. Clinical associations of the type I
      IFN pathway and the use of IFN-blocking agents as therapeutic agents in SLE are
      also reviewed.

PMID- 21859346
TI  - Career flexibility and family-friendly policies: an NIH-funded study to enhance
      women's careers in biomedical sciences.
AB  - BACKGROUND: Although women receive nearly half of all doctoral degrees and show a
      high interest in academic careers, the pipeline is leaky. The challenge of
      balancing life course events with career trajectory is an important determinant
      leading to premature dropout or slower career advancement. This report describes
      the findings of the first phase of a National Institute of Health Office of
      Research on Women's Health (NIH ORWH)-funded study using survey and academic data
      for exploring satisfaction and awareness of/intent to use specific career
      flexibility options at the University of California, Davis (UCD). METHODS: All
      men and women faculty in the UCD's Schools of Medicine (SOM) and Veterinary
      Medicine (SVM) and College of Biological Science (CBS) were surveyed. Data also
      were obtained from deans' offices on use of family-friendly benefits by faculty.
      RESULTS: Three hundred twenty-five total survey responses were received from the
      SOM, 83 from SVM, and 64 from CBS, representing 42%, 46%, and 52% of their total
      faculty, respectively. In each school, large percentages of men (32%-60%) and
      women (46%-53%) faculty have children under 18 and a moderately high level of
      demand of family care responsibilities. Women were significantly more likely to
      be childless, particularly in the SOM (35% vs. 14%, p<0.001). For all schools,
      documented use of any family-friendly policy was low (0%-11.5%), as was awareness
      of policies, although both were significantly higher for women than for men.
      Significantly more women than men wanted to use policies or chose not to,
      particularly in the SOM (51% vs. 28%, p<0.001, and 37% vs. 23%, p=0.016,
      respectively), because of multiple barriers. Faculty in all schools agreed/highly
      agreed that policies were important to recruitment, retention, and career
      advancement. CONCLUSIONS: Family-friendly policies are pertinent to men and
      women, as both demonstrate interest and need, linked to increased career
      satisfaction. A family-friendly policy is important, particularly for women in
      the biomedical sciences.

PMID- 21859348
TI  - Sleep telemedicine: patient satisfaction and treatment adherence.
AB  - OBJECTIVE: Obstructive sleep apnea is common, but access to diagnosis remains
      limited. Telemedicine may allow greater access to care; however, its effect on
      patient satisfaction and treatment adherence is unknown. This study compares
      patient satisfaction and continuous positive airway pressure (CPAP) adherence of
      patients seen by videoconference with those seen in person. MATERIALS AND
      METHODS: New patients seen via video or in person at a sleep center completed a
      survey, with three questions pertaining to satisfaction with the provider.
      Questions were scored 1-5; the sum was the patient satisfaction score. CPAP
      adherence was retrospectively analyzed in patients who met the physician via
      video or in person. Percentage of nights CPAP was used for >=4 h and average
      minutes of CPAP use per night over 2 consecutive weeks were compared. RESULTS: A
      Mann-Whitney test compared patient satisfaction of the 90 subjects (of whom, 56
      met physician in person and 34 via video). Mean scores (in person, 14.82; video,
      14.91; p=0.851) did not differ between groups. Mann-Whitney tests compared CPAP
      adherence in the 172 subjects (of whom, 111 met physician in person and 61 via
      video). Mean percentage of nights CPAP was used >=4 h (in person, 71%; video,
      65%; p=0.198) and the average minutes per night of CPAP use (in person, 340.55;
      video, 305.31; p=0.153) did not differ between groups. CONCLUSIONS: The findings
      indicate that patients were equally satisfied with their provider and adherent to
      CPAP treatment whether they were seen in person or via video. Videoconferencing
      may improve access to patient care without reducing patient satisfaction or
      treatment adherence.

PMID- 21859347
TI  - Using telehealth to provide diabetes care to patients in rural Montana: findings
      from the promoting realistic individual self-management program.
AB  - OBJECTIVE: The objectives of this study were to demonstrate the feasibility of
      telehealth technology to provide a team approach to diabetes care for rural
      patients and determine its effect on patient outcomes when compared with face-to
      face diabetes visits. MATERIALS AND METHODS: An evaluation of a patient-centered
      interdisciplinary team approach to diabetes management compared telehealth with
      face-to-face visits on receipt of recommended preventive guidelines, vascular
      risk factor control, patient satisfaction, and diabetes self-management at
      baseline and 1, 2, and 3 years postintervention. RESULTS: One-year
      postintervention the receipt of recommended dilated eye exams increased 31% and
      43% among telehealth and face-to-face patients, respectively (p=0.28). Control of
      two or more risk factors increased 37% and 69% (p=0.21). Patient diabetes care
      satisfaction rates increased 191% and 131% among telehealth and face-to-face
      patients, respectively (p=0.51). A comparison of telehealth with face-to-face
      patients resulted in increased self-reported blood glucose monitoring as
      instructed (97% vs. 89%; p=0.63) and increased dietary adherence (244% vs. 159%;
      p=0.86), respectively. Receipt of a monofilament foot test showed a significantly
      greater improvement among face-to-face patients (17% vs. 35%; p=0.01) at 1 year
      postintervention, but this difference disappeared in years 2 and 3. CONCLUSIONS:
      Telehealth proved to be an effective mode for the provision of diabetes care to
      rural patients. Few differences were detected in the delivery of a team approach
      to diabetes management via telehealth compared with face-to-face visits on
      receipt of preventive care services, vascular risk factor control, patient
      satisfaction, and patient self-management. A team approach using telehealth may
      be a viable strategy for addressing the unique challenges faced by patients
      living in rural communities.

PMID- 21859349
TI  - Antioxidant and anti-inflammatory activities of quercetin 7-O-beta-D
      glucopyranoside from the leaves of Brasenia schreberi.
AB  - Brasenia schreberi Gmel. (Cabombaceae) is an aquatic plant that grows in eastern
      Asia, Australia, Africa, and North and Central America. B. schreberi leaf
      extracts were obtained by sequential solvent extraction with dichloromethane,
      methanol, and water. The antioxidant potential of each extract was assessed by
      using the oxygen radical absorbance capacity (ORAC) assay. With this method,
      methanol and water extracts were found to be active with mean +/- standard
      deviation values of 7 +/- 2 and 5.1 +/- 0.5 MUmol Trolox(r) equivalents (TE)/mg,
      respectively. Two major phenolic compounds, quercetin-7-O-beta-D-glucopyranoside
      and gallic acid, were respectively isolated from the methanolic and water
      extracts. Both compounds exhibited antioxidant activities, in particular
      quercetin-7-O-beta-D-glucopyranoside (ORAC value, 18 +/- 4  MUmol TE/MUmol). In
      contrast to its well-known antioxidant homologue quercetin, quercetin-7-O-beta-D
      glucopyranoside does not inhibit growth of human fibroblasts (WS-1) or murine
      macrophages (RAW 264.7). Some flavonoids have been reported to possess beneficial
      effects in cardiovascular and chronic inflammatory diseases associated with
      overproduction of nitric oxide. Quercetin-7-O-beta-D-glucopyranoside possesses
      anti-inflammatory activity, inhibiting expression of inducible nitric oxide
      synthase and release of nitric oxide by lipopolysaccharide-stimulated RAW 264.7
      macrophages in a dose-dependent manner. Quercetin-7-O-beta-D-glucopyranoside also
      inhibited overexpression of cyclooxygenase-2 and granulocyte macrophage-colony
      stimulating factor.

PMID- 21859350
TI  - Honey and microbial infections: a review supporting the use of honey for
      microbial control.
AB  - Honey has been used as a medicine throughout the ages and has recently been
      reintroduced to modern medical practice. Much of the research to date has
      addressed honey's antibacterial properties and its effects on wound healing.
      Laboratory studies and clinical trials have shown that honey is an effective
      broad-spectrum antibacterial agent. Honey antimicrobial action explains the
      external and internal uses of honey. Honey has been used to treat adult and
      neonatal postoperative infection, burns, necrotizing fasciitis, infected and
      nonhealing wounds and ulcers, boils, pilonidal sinus, venous ulcers, and diabetic
      foot ulcers. These effects are ascribed to honey's antibacterial action, which is
      due to acidity, hydrogen peroxide content, osmotic effect, nutritional and
      antioxidants content, stimulation of immunity, and to unidentified compounds.
      When ingested, honey also promotes healing and shows antibacterial action by
      decreasing prostaglandin levels, elevating nitric oxide levels, and exerting
      prebiotic effects. These factors play a major role in controlling inflammation
      and promoting microbial control and healing processes. This article reviews data
      supporting the effectiveness of natural honey in eradicating human pathogens and
      discusses the mechanism of actions.

PMID- 21859352
TI  - Anti-hyperglycemia properties of Tea (Camellia sinensis) bioactives using in
      vitro assay models and influence of extraction time.
AB  - Tea (Camellia sinensis) has well-known health benefits, which are attributed to
      its polyphenolic metabolites. This research explored the potential of regular tea
      consumption and influence of extraction time typically used in daily consumption
      of tea, as a therapeutic dietary support for potential management of early stage
      type 2 diabetes using in vitro assay models. Extraction times of 2 and 5 minutes
      were compared. The 5-minute extraction time had significantly higher total
      phenolic content compared with the 2-minute extraction time. Choice Darjeeling 5
      minute extraction yielded the highest amount of total phenolics (299.6 +/- 5.9
      mg/g), followed by Tazo Black 5-minute extraction (240 +/- 9.7 mg/g), whereas
      Bigelow Green 2-minute extraction had the lowest total phenolic content (53 +/-
      8.2 mg/g). 1,1-Diphenyl-2-picrylhydrazyl scavenging-linked antioxidant activity
      was high (81-91%) for all types evaluated, and for most samples it was influenced
      by the extraction time. Similarly, high in vitro alpha-glucosidase inhibition was
      observed in almost all the samples assayed, and for most samples the 5-minute
      extraction had significantly higher inhibition compared with the 2-minute
      extraction time. The most fermented teas showed highest alpha-amylase inhibition:
      Choice Darjeeling 5-minute extraction had the highest inhibition (84.1%),
      followed by Tazo Black 5-minute extraction (71.6%). Angiotensin converting enzyme
      inhibition was not observed in any sample. Overall, the 5-minute extraction time
      was found to have more relevance for potential benefits for managing
      hyperglycemia than the 2-minute procedure. This research suggests that tea offers
      an attractive potential strategy to regulate postprandial hyperglycemia toward an
      overall dietary support for type 2 diabetes management.

PMID- 21859351
TI  - Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in
      Swiss albino mice.
AB  - The aim of the present study was to investigate the protective role of Ginkgo
      biloba L. leaf extract against the active agent of Roundup(r) herbicide
      (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided
      into six groups, with each group consisting of six animals: Group I (control)
      received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only),
      Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III
      received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G.
      biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50
      mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI
      received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body
      weight). The single dose of glyphosate was given intraperitoneally. Animals from
      all the groups were sacrificed at the end of 72 hours, and their blood, bone
      marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine,
      malondialdehyde (MDA), and glutathione (GSH) levels and the presence of
      micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The
      results indicated that serum AST, ALT, BUN, and creatinine levels significantly
      increased in mice treated with glyphosate alone compared with the other groups
      (P<.05). Besides, glyphosate-induced oxidative damage caused a significant
      decrease in GSH levels and a significant increase in MDA levels of the liver and
      kidney tissues. Moreover, glyphosate alone-treated mice presented higher
      frequencies of CAs, MNs, and abnormal metaphases compared with the controls
      (P<.05). These mice also displayed a lower mean mitotic index than the controls
      (P<.05). Treatment with G. biloba produced amelioration in indices of
      hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to
      Group II. Each dose of G. biloba provided significant protection against
      glyphosate-induced toxicity, and the strongest effect was observed at a dose of
      150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is
      a potent protector against glyphosate-induced toxicity, and its protective role
      is dose-dependent.

PMID- 21859353
TI  - Multifocal intracranial germinoma with raised tumour markers in serum but not in
      CSF and with carcinoma in situ of the testis.

PMID- 21859354
TI  - Severe systemic vasoconstriction starting with acute limb ischemia leading to
      death in a patient with well-differentiated pulmonary neuroendocrine carcinoma: a
      new paraneoplastic syndrome?

PMID- 21859355
TI  - Therapy-related myeloid neoplasms in epithelial ovarian cancer patients carrying
      BRCA1 mutation: report of two cases.

PMID- 21859356
TI  - Targeted therapy in cancer care - a critical snapshot.

PMID- 21859357
TI  - Mean platelet volume in predicting short- and long-term morbidity and mortality
      in patients with or without ST-segment elevation myocardial infarction.
AB  - Mean platelet volume (MPV) is a marker of platelet activation. An increased MPV
      is associated with acute myocardial infarction (AMI) and long-term mortality. The
      aim of this study was to compare MPV in patients with ST-segment elevation
      myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction
      (NSTEMI). Also, we investigated the value of MPV on in-hospital mortality and
      long-term prognosis of patients with STEMI and NSTEMI. We studied 429 patients
      with AMI (70.4% male, 61.9 +/- 12.4 years; 279 patients with STEMI, 150 patients
      with NSTEMI). MPV and platelet count were similar in both groups. Elevated MPV
      increased the risk of death by 3.1-fold (p < 0.001) in STEMI group during the
      hospitalization. However, increased MPV was not associated with in-hospital
      mortality in NSTEMI group. The area under the receiver operating characteristic
      curve of MPV was 0.868 (95% CI, 0.830-0.907) for predicting two-year mortality. A
      cut-off point of 11.1 fL showed a sensitivity of 81% and a specifity of 77% for
      prediction of two-year mortality. Kaplan-Meier survival curve showed two-year
      mortality rate of 12.5% in patients with MPV >11.1 fL versus 9.9% in patients
      with MPV <11.1 fL (p < 0.001). Cox regression analysis showed MPV to be an
      independent predictor of two-year mortality (Hazard ratio 1.7; 95% CI 1.5-1.9; p
      < 0.001). An increased MPV is an independent predictor of in-hospital mortality
      in patients with STEMI. However, elevated levels of MPV did not predict in
      hospital mortality in NSTEMI group. The increase in MPV values was independently
      correlated with two-year mortality in all study patients.

PMID- 21859358
TI  - Serum osteocalcin levels in patients with nonalcoholic fatty liver disease:
      association with ballooning degeneration.
AB  - Our aim was to examine the relation of serum osteocalcin (OCN) levels with the
      clinical, biochemical, and histological characteristics of patients with biopsy
      proven nonalcoholic fatty liver disease (NAFLD). We carried out a case-control
      study including 99 patients with biopsy-proven NAFLD and 75 age- and sex-matched
      controls. Concentrations of OCN were measured in aprotinin-treated serum samples
      using a solid-phase enzyme amplified sensitivity immunoassay. Serum OCN levels
      were significantly lower in patients with NAFLD than in healthy controls. In
      patients with NAFLD, serum OCN levels were inversely associated with ALT (r = 
      0.36, p < 0.001), AST (r =-0.39, p < 0.001), HOMA-IR (r = -0.30, p < 0.01) and
      the degree of hepatocyte ballooning (r =-0.20, p < 0.05). Serum OCN was the only
      independent predictor of the degree of hepatocyte ballooning in NAFLD patients
      (beta = -0.24; t = -2.146, p < 0.05). Compared with controls, NAFLD patients have
      a decrease in serum OCN concentrations, which is significantly associated with
      serum transaminases and the extent of hepatocyte ballooning.

PMID- 21859359
TI  - Genotoxic effects of profenofos on the marine fish, Therapon jarbua.
AB  - Profenofos (EC(50)) is a persistent and toxic organophosphorus insecticide.
      Animals get exposed to profenofos via food and water. The present study was
      designed to explore the genotoxic effect of profenofos in the marine fish. The
      ubiquitously occurring marine fish, Therapon jarbua, was exposed to profenofos
      and its effect on DNA was measured using comet (single-cell gel electrophoresis)
      assay. DNA damage were scored using mean percentage of tail length and compared
      with the comet classes' viz., 0, 1, 2, 3, and 4. In the first three doses, the
      (21.5, 43.0 and 86.0 ug L(-1)) comets were observed, of which the mean tail
      length differed significantly (p < 0.01) from those of unexposed, but not from
      each other. The mean tail length values were significantly (p < 0.05) higher in
      gill than in matured erythrocytes. The result indicates that DNA strand breaks in
      T. jarbua were due to the genotoxic potential of profenofos. From the study, we
      suggest that T. jarbua may be used as an indicator organism to assess the
      genotoxic risks of profenofos contamination in marine environments using Comet
      assay as an identification tool. We infer that organophosphorus insecticides may
      be dangerous to the marine lives.

PMID- 21859360
TI  - An improved brine shrimp larvae lethality microwell test method.
AB  - This article described an improved brine shrimp larvae lethality microwell test
      method. A simply designed connecting vessel with alternative photoperiod was used
      to culture and collect high yield of active Artemia parthenogenetica nauplii for
      brine shrimp larvae lethality microwell test. Using this method, pure A.
      parthenogenetica nauplii suspension was easily cultured and harvested with high
      density about 100-150 larvae per milliliter and the natural mortality was reduced
      to near zero by elimination of unnecessary artificial disturbance. And its
      sensitivity was validated by determination of LC(50)-24 h of different reference
      toxicants including five antitumor agents, two pesticides, three organic
      pollutants, and four heavy metals salts, most of which exhibited LC(50)-24 h
      between 0.07 and 58.43 mg/L except for bleomycin and mitomycin C with LC(50)-24 h
      over 300 mg/L.

PMID- 21859361
TI  - Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced
      redox imbalance in mice lungs.
AB  - The objective of the present study was to evaluate the effects of curcumin alone
      and with adjuvant piperine against benzo(a)pyrene (BaP) induced oxidative stress
      in lungs of male Swiss albino mice. Mice were pretreated either with curcumin
      (100 mg/kg body weight), or piperine (20 mg/kg body weight), and in combination
      of both for one week, followed by single dose of benzo(a)pyrene (125 mg/kg body
      weight) treatment. Treatment with benzo(a)pyrene resulted in increased levels of
      lipid peroxides (LPO), protein carbonyl content (PCC) and with consequent
      decrease in the levels of tissue antioxidants like superoxide dismutase (SOD),
      catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and
      reduced glutathione (GSH), which however, were increased significantly following
      curcumin treatment, but the increase was more pronounced when piperine was used
      as an adjuvant. BaP treatment alone did not alter significantly the GST activity.
      Pretreatment with curcumin increased the GST activity in BaP treated group, which
      was enhanced further upon synergistic treatment with piperine and curcumin.
      Therefore, combined administration of curcumin and piperine shall prove to be
      more effective in attenuating BaP induced toxicity.

PMID- 21859362
TI  - Ziram activates mitogen-activated protein kinases and decreases cytolytic protein
      levels in human natural killer cells.
AB  - Human natural killer (NK) cells are central in immune defense with their ability
      to lyse tumor cells and virally infected cells. Tumor formation and viral
      infection may increase if NK cytotoxic function is disrupted. Ziram (zinc
      dithiocarbamate) is used as an accelerating agent in the production of latex and
      to protect various fruits and vegetables from fungal infection. Previously, we
      have shown that exposure to ziram inhibits NK lytic function. Butyltin
      environmental contaminants, which also inhibit NK lytic function, cause rapid
      activations of mitogen-activated protein kinases (MAPKs) and decreases in
      expression of the cytolytic proteins granzyme B and perforin (after 24 h) in
      exposed NK cells. MAPKs are important regulators of the lytic response of NK
      cells, and spurious activation of these enzymes by contaminants would leave the
      NK cells unable to respond to appropriate targets. This study examined the
      effects of ziram exposures on MAPKs (p44/42, p38, and c-jun-N-terminal kinase)
      and on levels of cytolytic proteins. Ten-minute to 6-h exposures of NK cells to
      ziram caused activation of MAPKs, p44/42, and p38. Exposure to ziram for 24 h
      caused a decrease in granzyme B and perforin levels. MAPK inhibitors were able to
      prevent these ziram-induced decreases in granzyme B and perforin. These results
      suggest that ziram-induced MAPK activation is at least in part responsible for
      decreased cytolytic function in ziram-exposed NK cells. Furthermore, the results
      indicate that these changes are in common with other environmental contaminants
      that have been shown to decrease NK lytic function.

PMID- 21859364
TI  - Elevated adenosine deaminase activity in overweight and obese Indian subjects.
AB  - OBJECTIVE: To determine adenosine deaminase activity in overweight and obese
      Indian subjects. METHODS: This study comprised of 100 subjects. The body mass
      index (BMI) of subjects was calculated and adenosine deaminase activity was
      determined in their fasting blood sample. The study was divided into three groups
      depending upon BMI: Control (n = 40, BMI < 25 kg/m(2)), Overweight (n = 30, BMI
      25-29.9 kg/m(2)) and Obese (n = 30, BMI >= 30 kg/m(2)). RESULTS: The serum
      adenosine deaminase activity was significantly increased in overweight and obese
      subjects and as well as in combined overweight and obese group as compared to
      control (P < 0.0001). CONCLUSION: Adenosine, an endogenous anti-inflammatory
      metabolite, is increased in response to inflammation produced by adipose tissue
      in obesity. However, adenosine deaminase acts on adenosine to convert it into
      inosine, thereby increasing adenosine deaminase activity in overweight and obese
      Indian subjects.

PMID- 21859363
TI  - The effects of different sperm preparation methods and incubation time on the
      sperm DNA fragmentation.
AB  - PURPOSE: To study the effect of different sperm preparation methods and
      incubation times post preparation on sperm DNA fragmentation. METHODS: Sperm DNA
      fragmentation was assessed by sperm chromatin dispersion (SCD) method on motile
      sperm prepared by gradient centrifugation or swim-up and incubated in IVF medium
      for up to 24 hours. Data were analyzed to discover the effect of preparation
      methods and incubation times on sperm DNA Fragmentation Index (DFI). RESULTS:
      There were no differences in DFI in sperm samples prepared by gradient
      centrifugation method or swim-up (3.87 +/- 2.14 vs. 3.45 +/- 1.83, p = 0.544).
      However, an increase was observed in DFI in samples prepared by swim-up after 6-8
      hours compared with by gradient centrifugation (34 degrees  vs. 13 degrees , p =
      0.04). In the swim-up group, the DFI level at 4 hours was already significantly
      higher than it was initially. However, following gradient centrifugation, the DFI
      at 8 hours was significantly higher than the initial DFI level. CONCLUSION: Sperm
      samples prepared by gradient centrifugation may be more stable, in terms of DNA
      fragmentation, than samples prepared by swim-up.

PMID- 21859365
TI  - United States Voluntary Children's Chemical Evaluation Program (VCCEP) risk
      assessment for children exposed to benzene.
AB  - As part of the Voluntary Children's Chemical Evaluation Program (VCCEP) program,
      a risk assessment was performed to evaluate the risks to children from
      environmental benzene exposures. This paper summarizes this risk assessment. Risk
      was characterized using two distinct methods: USEPA's default type of risk
      assessment, which used the Reference Dose (RfD) and Cancer Slope Factor (CSF) to
      characterize non-cancer and cancer risks, as well as a Margin of Safety (MOS)
      approach that utilized a point of departure (POD). The exposures for most
      scenarios evaluated in this VCCEP risk assessment are lower than both the cancer
      and non-cancer PODs by several orders of magnitude, indicating a large MOS and
      corresponding low potential for toxicity at these exposures. The highest benzene
      exposures likely experienced by children, associated with the lowest MOS, are
      from cigarette smoke. In addition, the potential for age-related differences in
      the sensitivity towards benzene-induced toxicity was investigated. In general,
      this risk assessment does not indicate that children are likely to be at a
      elevated risk of AML or hematopoietic toxicity associated with environmental
      exposures to benzene.

PMID- 21859366
TI  - Efficacy and safety of oral iron(III) polymaltose complex versus ferrous sulfate
      in pregnant women with iron-deficiency anemia: a multicenter, randomized,
      controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of iron(III) polymaltose complex
      (Maltofer((r))) versus ferrous sulfate in iron-deficient pregnant women using
      recommended doses. METHODS: An exploratory, open-label, randomized, controlled,
      multicenter study was undertaken in 80 pregnant women with iron-deficiency anemia
      (hemoglobin <= 10.5 g/dL, serum ferritin <= 15 ng/mL and mean corpuscular volume
      < 80 fL). Patients were randomized 1:1 to oral iron(III) polymaltose complex or
      ferrous sulfate (each 100 mg iron twice daily) for 90 days. RESULTS: The primary
      endpoint, change in hemoglobin from baseline to days 60 and 90, did not differ
      significantly between treatment groups. The mean (SD) change to day 90 was 2.16
      (0.67) g/dL in the iron(III) polymaltose complex group and 1.93 (0.97) g/dL in
      the ferrous sulfate group (n.s). Mean serum ferritin at day 90 was 179 (38) ng/mL
      and 157 (34) ng/mL with iron(III) polymaltose complex and ferrous sulfate,
      respectively (p = 0.014). Adverse events were significantly less frequent in the
      iron(III) polymaltose group, occurring in 12/41 (29.3%) patients, than in the
      ferrous sulfate group (22/39 [56.4%]) (p = 0.015). CONCLUSIONS: Oral iron(III)
      polymaltose complex offers at least equivalent efficacy and a superior safety
      profile compared to ferrous sulfate for the treatment of iron-deficiency anemia
      during pregnancy.

PMID- 21859368
TI  - Development of attention functions in 5- to 11-year-old Arab children as measured
      by the German Test Battery of Attention Performance (KITAP): a pilot study from
      Syria.
AB  - We administered the German Test-battery of Attention Performance (KITAP) to Arab
      children living in Syria (N=143, 5-11 years) in order to assess the influence of
      age and gender on different dimensions of attention. The results demonstrate the
      validity of cross-cultural application of KITAP with Syrian school-aged children.
      The influence of age was more evident on speed of performance than on quality of
      performance, with rapid, general improvement until the age of 9 years. Some
      attention functions like alertness and inhibitory control seemed to be developed
      earlier than other functions like, flexibility, distractibility, and divided
      attention. Gender-related differences were observed in some subtests: Boys had
      faster reaction times but made more errors than girls. Interestingly, Arab-Syrian
      children showed better performance on some attention tests compared with German
      norms. The present study provides support for the use of cross-cultural studies
      for better understanding of the development of attention in school-aged children.

PMID- 21859367
TI  - Enhancement of antioxidant defense mechanism by pitavastatin and rosuvastatin on
      obesity-induced oxidative stress in Wistar rats.
AB  - CONTEXT: There has been a steady increase in the epidemiology of obesity over the
      last 30 years with developed countries leading the way. Oxidative stress was
      believed to be the principle contributor to the development of cardiovascular
      disorders that linked with obesity. OBJECTIVE: To evaluate the enhancement of
      antioxidant defense mechanism by Pitavastatin (PTV) and Rosuvastatin (RSV) on
      obesity-induced oxidative stress in Wistar rats. METHODS: Fifty Wistar albino
      rats were divided into five groups. High fat diet (HFD, 20 g/day/rat) pellets
      were given for 28 days to produce obesity-induced oxidative stress in Wistar
      rats. Oral administration of HFD along with PTV, RSV and Orlistat [(HFD for 28
      days + from 8th day PTV (1 mg/kg), RSV (5 mg/kg) and Orlistat (10 mg/kg) to 28th
      day] were given respectively. RESULTS: Both PTV and RSV produced significant (p <
      0.01) reduction in serum apolipoprotein-B (Apo-B), total cholesterol (TC),
      triglycerides (TGs), cardiac-lipid peroxides (TBARS) levels and elevation in
      serum high density lipoprotein (HDL-C), cardiac antioxidant enzymes [glutathione
      (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S
      transferase (GST), superoxide dismutase (SOD) and catase (CAT)] levels.
      DISCUSSION AND CONCLUSION: Results were comparable with Orlistat, a standard
      antiobesity drug and present initial evidence that Pitavastatin and Rosuvastatin
      are useful for the treatment of obesity by enhancing the antioxidant defense
      mechanism. However, the effects of PTV were more prominent than RSV. The present
      findings of Pitavastatin and Rosuvastatin raise the possibility of a new
      application as an antiobesity therapeutic modality.

PMID- 21859369
TI  - Volatile components of ethanolic extract from broccolini leaves.
AB  - Broccolini (Brassica oleracea Italica * Alboglabra) is a hybrid of broccoli and
      kai-lan, Chinese broccoli. To date, no study has been reported on the chemical
      composition of the volatile fractions of this raw material. In this study, the
      volatile constituents from the ethanolic extract of broccolini leaves were
      analysed by gas chromatography-mass spectrometry (GC-MS). Sixteen compounds were
      identified. The major components include 5-phenyl-undecane (11%), n-hexadecanoic
      acid (9.34%), octadecanoic acid (6.39%), 1,1,3-trimethyl-3-phenyl-indan (4.0%), 3
      (2-phenylethyl)benzonitrile (3.48%) and phytol (3.37%).

PMID- 21859370
TI  - Quantitative analysis of sulphated glycosaminoglycans content of Malaysian sea
      cucumber Stichopus hermanni and Stichopus vastus.
AB  - Stichopus hermanni and Stichopus vastus are sea cucumber species from the
      Stichopodidae family within the coastal waters of Malaysia. The integument of
      these invertebrates is hypothesised to contain abundant glycosaminoglycans
      (GAGs). GAGs are divided into non-sulphated and sulphated GAGs. Sulphated GAGs
      have various chemico-biological functions that are beneficial to humans. This
      study quantitatively analysed N-, O-sulphated and total sulphated GAG content
      from three different anatomical regions (integument, internal organs and coelomic
      fluid) of S. hermanni and S. vastus. The integument revealed the highest content
      of total, O- and N-sulphated GAGs, followed by the internal organs and the
      coelomic fluid for both species of sea cucumbers. The percentage division of O-
      and N-sulphated GAGs suggested that anatomical parts of both species showed
      higher levels of O-sulphated GAGs compared to N-sulphated GAGs. In conclusion,
      these findings indicate that the integument body wall of S. hermanni and S.
      vastus is a rich source of sulphated GAGs.

PMID- 21859371
TI  - Antioxidant activity of organic and aqueous leaf extracts of Cassia occidentalis
      L. in relation to their phenolic content.
AB  - In this study, the antioxidant potency of sequential organic and aqueous leaf
      extracts of Cassia occidentalis was investigated, employing various established
      in vitro systems such as nitric oxide scavenging (NOS) activity, beta-carotene
      linoleic acid model system, hydroxyl radical scavenging (HRS) activity, reducing
      power, metal chelating activity (MCA) and superoxide radical scavenging (SRS)
      activity. The aqueous extract of the leaves of C. occidentalis was found to be
      most effective against free radicals, followed by the methanolic, chloroform,
      petroleum ether and benzene extracts, respectively. A preliminary study of
      qualitative and quantitative estimations of phenolics was performed, and the
      results were correlated with different antioxidant tests. A positive and
      significant (p < 0.05) correlation was observed (R2 = 0.42 to 0.96) between
      various test systems, and the results on total phenolics showed that the phenolic
      compounds were responsible for the antioxidant capacity of the extracts. This
      study also showed that phenolics may contribute maximally to HRS (R2 = 0.9236)
      and MCA (R2 = 0.9396) and to a lesser extent to NOS activity (R2 = 0.5819) and
      the beta-carotene-linoleic acid assay (R2 = 0.8213). The data obtained in the in
      vitro models clearly establish the antioxidant potency of leaf extracts of C.
      occidentalis.

PMID- 21859372
TI  - Phytochemical and in vitro screening of some Ficus and Morus spp. for
      hypolipidaemic and antioxidant activities and in vivo assessment of Ficus
      mysorensis (Roth).
AB  - Phytochemical screening of air-dried leaves and fruit juice of certain Ficus and
      Morus spp. have been studied. In an in vitro study, the ethanol and hexane
      extracts of the investigated plants were evaluated against hyperlipidaemia by
      estimating the rate limiting enzyme of cholesterol biothenysis; beta-hydroxy-beta
      methylglutaryl coenzyme A reductase (HMG-CoA reductase). The antioxidant activity
      was evaluated by reduction of DPPH(-) free radical. Extra phytochemical screening
      of Ficus extracts was undertaken, which recorded potent hypolipidaemic and
      antioxidant activities. The more pronounced extract, Ficus mysorensis (hexane
      extract), was evaluated in vivo by estimation of the lipid profile and certain
      antioxidant parameters in hypercholesterolemic rats. The hexane fraction was
      chromatographed and six isolated compounds were identified. Furthermore, its
      saponifiable fraction was identified by a MS/MS technique. In conclusion, F.
      mysorensis recorded hypolipidaemic and antioxidant effects. Detailed studies of
      the isolated compounds must be undertaken for an evaluation against
      hypercholesterolemia and free radical elevation.

PMID- 21859373
TI  - Rapid access to ketones related to oleanolic and ursolic acids.
AB  - We describe in this article a process with which to obtain different ketones
      related to oleanolic and ursolic acids from a natural source, Salvia canariensis
      L., with minimal use of chromatography columns. Amongst the isolated compounds
      was 12alpha-bromo-3-oxo-olean-13, 28-olide (3), which was fully characterised,
      including a characterisation of its molecular configuration by X-ray
      crystallographic analysis by 1 and 2-dimensional NMR techniques.

PMID- 21859374
TI  - Determination of tocopherol contents of some olive varieties harvested at
      different ripening periods.
AB  - The tocopherol contents of oils obtained from Ayvalik, Domat and Gemlik olive
      varieties harvested at different ripening periods were evaluated by high
      performance liquid chromatography. alpha-Tocopherol was the major tocol detected
      in all the studied olive oil samples. The oils extracted from olive fruits
      composed of 130.54-180.43 mg kg-1 alpha-tocopherol, 0.73-1.61 mg kg-1 beta
      tocopherol and 0.53-2.28 mg kg-1 gamma-tocopherol for Ayvalik oil. The alpha-,
      beta- and gamma-tocopherol contents of Domat oil are in the ranges 95.60-125.56,
      0.71-2.70 and 0.49-1.25 mg kg-1 at different harvesting periods. The alpha-, beta
      and gamma-tocopherol contents of Gemlik olive oil are in the ranges 112.59
      168.19, 0.94-1.21 and 0.85-2.40 mg kg-1, respectively. There were significant
      differences between the oils from cultivars grown in different environments.

PMID- 21859375
TI  - Differentiation of Schisandra chinensis and Schisandra sphenanthera using
      metabolite profiles based on UPLC-MS and GC-MS.
AB  - Historically, Schisandra chinensis and S. sphenanthera have been widely used in
      traditional Chinese medicine. Although both species are in the genus Schisandra,
      they have dissimilar therapeutic effects that may be attributed to compositional
      differences in secondary metabolites. We developed a method to compare these
      metabolites obtained from the above plant species using ultra-performance liquid
      chromatography-mass spectrometry and gas chromatography-mass spectrometry coupled
      with multivariate statistical analyses. The critical markers we used to
      discriminate between both plant species resulted in the identification and
      quantification of six lignans and seven essential oils. We believe that our
      approach provided a sensitive, reliable and robust method to conveniently
      classify medicinal plants that can be used to explore subtle variations among
      different species or plants from different geographical locations.

PMID- 21859377
TI  - In vitro and in vivo small intestinal metabolism of CYP3A and UGT substrates in
      preclinical animals species and humans: species differences.
AB  - Intestinal first-pass metabolism has a great impact on the bioavailability of
      cytochrome P450 3A4 (CYP3A) and/or uridine 5'-diphosphate (UDP)
      glucoronosyltranferase (UGT) substrates in humans. In vitro and in vivo
      intestinal metabolism studies are essential for clarifying pharmacokinetics in
      animal species and for predicting the effects of human intestinal metabolism. We
      review species differences in intestinal metabolism both in vitro and in vivo.
      Based on mRNA expression levels, the major intestinal CYP3A isoform is CYP3A4 for
      humans, CYP3A4 (3A8) for monkeys, CYP3A9 for rats, cyp3a13 for mice, and CYP3A12
      for dogs. Additionally, the intestinal-specific UGT would be UGT1A10 for humans,
      UGT1A8 for monkeys, and UGT1A7 for rats. In vitro and in vivo intestinal
      metabolism of CYP3A substrates were larger in monkeys than in humans, although a
      correlation in intestinal availability between monkeys and humans has been
      reported. Little information is available regarding species differences in in
      vitro and in vivo UGT activities; however, UGT-mediated in vivo intestinal
      metabolism has been demonstrated for raloxifene in humans and for baicalein in
      rats. Further assessment of intestinal metabolism, particularly for UGT
      substrates, is required to clarify the entire picture of species differences.

PMID- 21859376
TI  - Cytotoxic effects of Mn(III) N-alkylpyridylporphyrins in the presence of cellular
      reductant, ascorbate.
AB  - Due to the ability to easily accept and donate electrons Mn(III)N
      alkylpyridylporphyrins (MnPs) can dismute O(2)(.-), reduce peroxynitrite, but
      also generate reactive species and behave as pro-oxidants if conditions favour
      such action. Herein two ortho isomers, MnTE-2-PyP(5+), MnTnHex-2-PyP(5+), and a
      meta isomer MnTnHex-3-PyP(5+), which differ greatly with regard to their metal
      centered reduction potential, E(1/2) (Mn(III)P/Mn(II)P) and lipophilicity, were
      explored. Employing Mn(III)P/Mn(II)P redox system for coupling with ascorbate,
      these MnPs catalyze ascorbate oxidation and thus peroxide production.
      Consequently, cancer oxidative burden may be enhanced, which in turn would
      suppress its growth. Cytotoxic effects on Caco-2, Hela, 4T1, HCT116 and SUM149
      were studied. When combined with ascorbate, MnPs killed cancer cells via peroxide
      produced outside of the cell. MnTE-2-PyP(5+) was the most efficacious catalyst
      for peroxide production, while MnTnHex-3-PyP(5+) is most prone to oxidative
      degradation with H(2) , and thus the least efficacious. A 4T1 breast cancer mouse
      study of limited scope and success was conducted. The tumour oxidative stress was
      enhanced and its microvessel density reduced when mice were treated either with
      ascorbate or MnP/ascorbate; the trend towards tumour growth suppression was
      detected.

PMID- 21859378
TI  - Clinical and epidemiological features of Turkish children with 2009 pandemic
      influenza A (H1N1) infection: experience from multiple tertiary paediatric
      centres in Turkey.
AB  - BACKGROUND: In April 2009 a novel strain of human influenza A, identified as H1N1
      virus, rapidly spread worldwide, and in early June 2009 the World Health
      Organization raised the pandemic alert level to phase 6. Herein we present the
      largest series of children who were hospitalized due to pandemic H1N1 infection
      in Turkey. METHODS: We conducted a retrospective multicentre analysis of case
      records involving children hospitalized with influenza-like illness, in whom 2009
      H1N1 influenza was diagnosed by reverse-transcriptase polymerase chain reaction
      assay, at 17 different tertiary hospitals. RESULTS: A total of 821 children with
      2009 pandemic H1N1 were hospitalized. The majority of admitted children (56.9%)
      were younger than 5 y of age. Three hundred and seventy-six children (45.8%) had
      1 or more pre-existing conditions. Respiratory complications including wheezing,
      pneumonia, pneumothorax, pneumomediastinum, and hypoxemia were seen in 272
      (33.2%) children. Ninety of the patients (11.0%) were admitted or transferred to
      the paediatric intensive care units (PICU) and 52 (6.3%) received mechanical
      ventilation. Thirty-five children (4.3%) died. The mortality rate did not differ
      between age groups. Of the patients who died, 25.7% were healthy before the H1N1
      virus infection. However, the death rate was significantly higher in patients
      with malignancy, chronic neurological disease, immunosuppressive therapy, at
      least 1 pre-existing condition, and respiratory complications. The most common
      causes of mortality were pneumonia and sepsis. CONCLUSIONS: In Turkey, 2009 H1N1
      infection caused high mortality and PICU admission due to severe respiratory
      illness and complications, especially in children with an underlying condition.

PMID- 21859382
TI  - Honey as a substitute for formalin?
AB  - Formalin has long been the standard fixative for clinical routines worldwide.
      After the Formaldehyde Standard became law in the US in 1987, as a result of
      increasing concerns about the potential carcinogenicity of formaldehyde, attempts
      have been made to find safer alternatives. Alcoholic formalin is a useful
      fixative, because in addition to fixation, dehydration also is begun. For
      centuries, honey has been known to be an antibacterial agent with the potential
      to preserve compounds without harmful effects on its users. We compared the
      effects of honey fixation with other routine fixatives using conventional
      histochemical and immunohistochemical staining methods. Our results demonstrated
      that tissues fixed in either honey or alcoholic formalin and 10% neutral buffered
      formalin (NBF) have similar histomorphology. Honey fixation showed minor
      histomorphological differences among the various tissues; however, it did not
      influence affect correct diagnostic conclusions. Our results suggested that honey
      can be used as a safe alternative to formalin in histopathology.

PMID- 21859383
TI  - Expression of smoothened in mouse embryonic maxillofacial development.
AB  - Hedgehog (Hh) signaling plays many key roles in the development of Drosophila and
      vertebrate embryos including regulation of craniofacial development. The seven
      transmembrane protein, smoothened (Smo) transduces the Hh signal across the
      plasma membrane as an essential receptor of PTCHED1/2. There are few studies that
      evaluate the detailed expression of Smo in mouse embryonic craniofacial
      development. We investigated the expression patterns of Smo during murine
      embryonic craniofacial development using in situ hybridization (ISH), studies of
      whole-mounts and sections, immunohistochemistry, quantitative real time PCR, and
      Western blot analysis. We found that Smo mRNA was expressed in the face of mouse
      embryos at 11 and 12.5 days post coitum (dpc). After 13.5 dpc, the expression
      decreased to a low level and was faintly detected after birth. Smo protein could
      be detected also in embryos at 11, 12.5, and 14.5 dpc. After 15.5 dpc, the
      expression was very faint and paralleled the gene expression studies. No
      expression was detected in whisker follicle during facial development and faint
      signal was detected in Meckel's cartilage. These findings concerning Smo
      expression should guide further investigation of sonic Hh signaling pathway gene
      function during maxillofacial development.

PMID- 21859385
TI  - Sporotrichosis in HIV-infected patients: report of 21 cases of endemic
      sporotrichosis in Rio de Janeiro, Brazil.
AB  - Sporotrichosis is endemic in Rio de Janeiro, Brazil, and cases have been reported
      to be associated with HIV. This article describes the clinical manifestations and
      evolution of sporotrichosis in HIV-positive patients and constitutes the largest
      case series reported to date. There were 21 HIV-positive patients with
      sporotrichosis diagnosed by the recovery of the etiologic agent from 1999-2009.
      Sixteen patients (76.2%) were men and five (23.8%) were women, with a mean age of
      41.2 years. Seven of these individuals were previously unaware of their HIV
      infection. Mean CD4 count was 346.4 cells/MUl. The most frequent clinical
      presentations of sporotrichosis in these patients were the lymphocutaneous and
      disseminated form (seven patients each, 33.3%), followed by the widespread
      cutaneous form in five (23.8%), and fixed form in the remaining two (9.5%). In
      patients with the disseminated forms, clinical manifestations involved the skin
      in six, mucosa (nasal, oral, or conjunctival) in four, bone in two, and meninges
      in two. Eleven (52.4%) patients received itraconazole and eight (38.1%)
      amphotericin B contributing to an overall cure rate of 81%. Spontaneous cure was
      observed in one patient. The clinical forms of sporotrichosis varied according to
      the patients' immune status. The results demonstrate the importance of
      sporotrichosis as an opportunistic infection associated with AIDS in countries
      where the mycosis occurs.

PMID- 21859386
TI  - Comparison of the FXGTM: RESP (Asp+) real-time PCR assay with direct
      immunofluorescence and calcofluor white staining for the detection of
      Pneumocystis jirovecii in respiratory specimens.
AB  - We compared the FXGTM: RESP (Asp +) real-time PCR assay (Myconostica Ltd) with
      two microscopic staining methods (direct immunofluorescence [IFA] and calcofluor
      white) for the detection of Pneumocystis jirovecii in 411 respiratory specimens
      submitted for P. jirovecii examination. We considered the specimen to be
      microscopically positive if the organism could be visualized through the use of
      either IFA or calcofluor white. A second, published real-time PCR assay targeting
      the cdc2 gene of P. jirovecii was used to adjudicate those specimens that were
      microscopically negative but Myconostica PCR positive. The Myconostica PCR
      positive samples were deemed to be true positives if they were concordant with
      microscopically positive results or if they were positive by the second PCR
      assay. As a result, the Myconostica PCR assay was found to be more sensitive than
      the two microscopy methods in detecting P. jirovecii (10.5% true positivity rate
      by PCR, 8.0% by immunofluorescence, and 7.1% by calcofluor white). The
      Myconostica PCR assay showed 93.5% sensitivity, 95.1% specificity, 70.5% positive
      predictive value, and 99.1% negative predictive value. Its high negative
      predictive value suggests a role of the Myconostica PCR assay in ruling out
      Pneumocystis pneumonia.

PMID- 21859387
TI  - Evaluation of repetitive sequence PCR and PCR-mass spectrometry for the
      identification of clinically relevant Candida species.
AB  - The application of molecular diagnostic methods may improve the timeliness and
      accuracy with which fungi are identified. A total of 76 well-characterized
      reference strains of clinically relevant Candida species and 61 clinical Candida
      isolates were tested by repetitive sequence PCR (rep-PCR) and PCR followed by
      electrospray ionization mass spectrometry (PCR/ESI-MS) and results compared
      against internal transcribed spacer (ITS) ribosomal RNA gene sequencing as a
      reference standard. Both rep-PCR and PCR/ESI-MS correctly identified 51 isolates
      to the species level. When method performance was evaluated based only on
      genospecies included in the reference libraries, both methods yielded an accuracy
      of 98.1%. It may be concluded that rep-PCR and PCR/ESI-MS are highly effective at
      identifying clinical isolates of Candida to the species level. These methods hold
      promise for improving the speed and accuracy of identification of Candida spp. in
      clinical mycology laboratories.

PMID- 21859388
TI  - Correlation of antifungal susceptibility and molecular type within the
      Cryptococcus neoformans/C. gattii species complex.
AB  - Members of the Cryptococcus neoformans/C. gattii species complex are grouped into
      eight molecular types, differing in their epidemiology, disease severity and
      geographic range. Recent in vitro antifungal susceptibility studies of isolates
      of the complex revealed contradictory results. The objective of the present study
      was to assess if this variation is random or correlates with different molecular
      types by testing the in vitro antifungal susceptibility of 18 C. neoformans
      (VNI), 11 C. gattii (VGI) and 38 C. gattii (VGII) strains from Brazil to eight
      antifungal drugs using the CLSI microdilution method. We herein report that the
      molecular type VGII is the least susceptible genotype, followed by VGI and VNI.
      This indicates a clear correlation between antifungal susceptibilities and
      genotypes of the causative cryptococcosis agents, emphasizing the importance of
      determining the molecular type as part of the clinical diagnostic process to
      enable an informed decision as to the most appropriate antifungal treatment.

PMID- 21859389
TI  - N-acetylglucosamine increases symptoms and fungal burden in a murine model of
      oral candidiasis.
AB  - The amino sugar N-acetylglucosamine (GlcNAc) is an in vitro inducer of the hyphal
      mode of growth of the opportunistic pathogen Candida albicans. The development of
      hyphae by C. albicans is considered to contribute to the pathogenesis of mucosal
      oral candidiasis. GlcNAc is also a commonly used nutritional supplement for the
      self-treatment of conditions such as arthritis. To date, no study has
      investigated whether ingestion of GlcNAc has an effect on the in vivo growth of
      C. albicans or the pathogenesis of a C. albicans infection. Using a murine model
      of oral candidiasis, we have found that administration of GlcNAc, but not
      glucose, increased oral symptoms of candidiasis and fungal burden. Groups of mice
      were given GlcNAc in either water or in a viscous carrier, i.e., 1%
      methylcellulose. There was a dose-dependent relationship between GlcNAc
      concentration and the severity of oral symptoms. Mice given the highest dose of
      GlcNAc, 45.2 mM, also showed a significant increase in fungal burden, and
      increased histological evidence of infection compared to controls given water
      alone. We propose that ingestion of GlcNAc, as a nutritional supplement, may have
      an impact on oral health in people susceptible to oral candidiasis.

PMID- 21859390
TI  - Allergic fungal sinusitis: innocence under suspicion.
AB  - The objective of this investigation was to explore the possibility of treating
      patients harboring invasive intracranial aspergillosis (InIA) at an early stage.
      Nineteen patients (age range 18-42 years) from a total of 114 cases of InIA seen
      from January 1999- December 2009 were included in this investigation. These
      individuals, all of whom had a past history of treated allergic fungal sinusitis
      (AFS) were evaluated as to their immune status, clinical presentations, time
      intervals and radiological findings. Past records of seven patients indicated
      skull base erosion and extension of the paranasal (PNS) masses into intracranial
      cavity, but none had neurological deficits or symptoms suggestive of raised
      intracranial pressure. All 19 patients had undergone endoscopic clearance of PNS
      during their first presentations. Both AFS and InIA were found simultaneously in
      seven patients, while the time-interval between the two forms was as long as 10
      years for two patients. Overall mortality was (8/19; 42%) with all deaths
      attributable to fungal meningo-encephalitis. As InIA carries a high mortality
      rate, it seems prudent to evaluate and treat these patients early in the course
      of their illness. The appearance of the invasive form of the disease in patients
      with a past history of AFS is not uncommon. The allergic form of disease may not
      be considered as a separate entity from InIA as both the pathologies may exist in
      same patient.

PMID- 21859391
TI  - Long-term surveillance and treatment of subclinical cryptococcosis and nasal
      colonization by Cryptococcus neoformans and C. gattii species complex in captive
      koalas (Phascolarctes cinereus).
AB  - Cryptococcosis is an important systemic mycosis caused by members of the
      Cryptococcus neoformans species complex. This disease is potentially fatal in
      various animals, including koalas. We describe the long-term surveillance and
      treatment of subclinical cryptococcosis and nasal colonization of koalas by
      Cryptococcus neoformans and C. gattii. Of the 15 animals investigated through the
      use of samples obtained by nasal swabs, antigen titer measurements, and
      pathologic examination, C. neoformans was found associated with nine koalas and
      C. gattii with one animal. Nine koalas showed subclinical disease and one
      clinical infections and antigenemia. Treatment with fluconazole, itraconazole and
      amphotericin B upon detection of C. neoformans or C. gattii was not effective.
      The results of the present study showed that C. neoformans was the predominant
      species isolated from the nasal swab samples and the fungus might have naturally
      become associated with the koalas' nasal cavities at Kanazawa Zoological Gardens.
      The unclear treatment effectiveness might have been caused by a shorter treatment
      period that is routinely used and unstable itraconazole absorption. This
      investigation also underscores the need for identifying effective treatment
      regimens for subclinical cryptococcosis and efficient measures for eradicating C.
      neoformans and C. gattii in koalas.

PMID- 21859392
TI  - Flavin monooxygenases, FMO1 and FMO3, not cytochrome P450 isoenzymes, contribute
      to metabolism of anti-tumour triazoloacridinone, C-1305, in liver microsomes and
      HepG2 cells.
AB  - 5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, being the close
      structural analogue of the clinically tested imidazoacridinone anti-tumour agent,
      C-1311, expressed high activity against experimental tumours and is expected to
      have more advantageous pharmacological properties than C-1311. The aim of this
      study was to elucidate the role of selected liver enzymes in the metabolism of C
      1305. We demonstrated that the studied triazoloacridinone was transformed with
      rat and human liver microsomes, HepG2 hepatoma cells and with human recombinant
      flavin-containing monooxygenases FMO1, FMO3 but not with CYPs. Furthermore, this
      compound was an effective inhibitor of CYP1A2 and CYP3A4. The product of FMO
      catalysed metabolism was shown to be identical to the main metabolite from liver
      microsomes and HepG2 cells. It was identified as an N-oxide derivative and, under
      hypoxia, it underwent retroreduction back to C-1305, what was extremely effective
      with participation of CYP3A4. In summary, this work revealed that the involvement
      of the P450 enzymatic system in microsomal and cellular metabolism of C-1305 was
      negligible, whereas this agent was an inhibitor of CYP1A2 and CYP3A4. In
      contrast, FMO1 and FMO3 were crucial for metabolism of C-1305 by liver microsomes
      and in HepG2 cells, which makes C-1305 an attractive potent anti-tumour agent.

PMID- 21859393
TI  - Disposition, metabolism and mass balance of [(14)C]apremilast following oral
      administration.
AB  - Apremilast is a novel, orally available small molecule that specifically inhibits
      PDE4 and thus modulates multiple pro- and anti-inflammatory mediators, and is
      currently under clinical development for the treatment of psoriasis and psoriatic
      arthritis. The pharmacokinetics and disposition of [(14)C]apremilast was
      investigated following a single oral dose (20 mg, 100 MUCi) to healthy male
      subjects. Approximately 58% of the radioactive dose was excreted in urine, while
      faeces contained 39%. Mean C(max), AUC(0-infinity) and t(max) values for
      apremilast in plasma were 333 ng/mL, 1970 ng*h/mL and 1.5 h. Apremilast was
      extensively metabolized via multiple pathways, with unchanged drug representing
      45% of the circulating radioactivity and <7% of the excreted radioactivity. The
      predominant metabolite was O-desmethyl apremilast glucuronide, representing 39%
      of plasma radioactivity and 34% of excreted radioactivity. The only other
      radioactive components that represented >4% of the excreted radioactivity were O
      demethylated apremilast and its hydrolysis product. Additional minor circulating
      and excreted compounds were formed via O-demethylation, O-deethylation, N
      deacetylation, hydroxylation, glucuronidation and/or hydrolysis. The major
      metabolites were at least 50-fold less pharmacologically active than apremilast.
      Metabolic clearance of apremilast was the major route of elimination, while non
      enzymatic hydrolysis and excretion of unchanged drug were involved to a lesser
      extent.

PMID- 21859394
TI  - One new and several minor diarylheptanoids from Amomum muricarpum.
AB  - A new natural diarylheptanoid, designated muricarpin, together with four
      diarylheptanoids were isolated from the rhizomes of Amomum muricarpum Elmer
      (Zingiberaceae) growing in Vietnam. Three known compounds, 1,7-bis(3,4
      dihydroxyphenyl)heptan-3-yl acetate, 1-(4'-hydroxyphenyl)-7- (3",4"
      dihydroxyphenyl)heptan-3-yl acetate and 1-(3',4'-dihydroxyphenyl)-7-(4"
      hydroxyphenyl)-heptan-3-one were isolated for the first time from the genus
      Amomum, meanwhile (5R)-5-hydroxy-1,7-bis(4-hydroxyphenyl)-heptan-3-one was found
      for the first time in plants. Their structures were determined using
      spectroscopic analyses.

PMID- 21859395
TI  - Validity of the fine motor area of the 12-month ages and stages questionnaire in
      infants following major surgery.
AB  - The Ages and Stages Questionnaires (ASQ) are parent-report screening tools to
      identify infants at risk of developmental difficulties. The purpose of this study
      was to examine validity and internal reliability of the fine motor developmental
      area of the ASQ, 2nd edition (ASQ2-FM) for screening 12-month-old infants
      following major surgery. The ASQ2-FM was completed by caregivers of 74 infants
      who had cardiac surgery in the first 90 days of life, 104 infants who had
      noncardiac surgery in the first 90 days of life, and a control group of 154
      infants. The Rasch item response analysis revealed that the ASQ2-FM had poor
      ability to discriminate among levels of fine motor ability. Sensitivity was poor
      (20%) and specificity was good (98%) when compared with the scores for the fine
      motor subscale of the Bayley Scales of Infant and Toddler Development. The ASQ2
      FM under-identified infants at risk for fine motor delay; internal reliability
      and construct validity do not support use as a screening tool of fine motor
      development of infants aged 12 months who have undergone major surgery.

PMID- 21859396
TI  - Internet addiction disorder: prevalence in an Italian student population.
AB  - BACKGROUND: Internet addiction is one of the latest forms of addiction that has
      attracted the attention of popular media and researchers in these last few years.
      Several authors think Internet addiction is a separate disorder that merits
      inclusion in DSM-V. There is considerable controversy about this opinion. AIMS:
      The aim of this study was to assess the prevalence of Internet addiction in a
      representative sample of high school students attending secondary institutions in
      the district of Cremona and to assess any difference concerning variables such as
      gender, age, place of residence and kind of school attended. METHODS: The Italian
      version of the Internet Addiction Test (IAT) has been administered to a sample of
      2533 students from different kinds of school. The survey also required social and
      demographic data. RESULTS: The majority of respondents were classified as normal
      users of the Internet (n = 2386, 94.19%), with 127 (5.01%) moderately addicted
      and 20 (0.79%) seriously addicted. Significant differences in gender and in kinds
      of school were found. No statistical differences were revealed in age and urban
      or rural conditions. CONCLUSIONS: Our study has confirmed the general use of the
      Internet among youngest people, the emergence of Internet addiction and the male
      preponderance of this phenomenon.

PMID- 21859397
TI  - Changes in mortality after first psychiatric admission: a 20-year prospective
      longitudinal clinical study.
AB  - OBJECTIVE: To examine changes in the mortality of patients admitted to a
      Norwegian psychiatric hospital from 1985 to 2003: this period saw profound
      changes in structure and organization of the mental healthcare system. METHOD: A
      20-year prospective longitudinal, record linkage study of all patients admitted
      to a psychiatric hospital with sector responsibility from 1985 to 2003. RESULTS:
      Excess mortality was found for the patient group. Overall standardized mortality
      ratio (SMR) (95% confidence interval, CI) was 2.85 (2.53-3.07)/2.15 (1.94-2.41)
      for male/female patients. One third of the patients who died in the study period
      died within 2 years after first admission, and 45% of the deaths happened within
      2 years after last discharge. The median age at death decreased in the study
      period for patients who were younger than 65 years at their first admission. The
      median difference of lost years of life for the patients younger than 65 years at
      first admittance was 26.95/23.96 years for male/female patients. SMR increased
      for the youngest cohorts during the study period over time. From 1985 to 2003,
      SMR increased dramatically for both genders. CONCLUSION: Patients admitted to a
      Norwegian psychiatric hospital for their first stay during 1985-2003 suffered
      increased excess mortality, whereas mortality in the general population
      decreased. The mortality was highest in the first 2 years after admission.
      Despite profound changes in the mental healthcare system, the mortality gap
      increased in the study period and was highest in the youngest birth cohorts.

PMID- 21859398
TI  - Potential action of betel alkaloids on positive and negative symptoms of
      schizophrenia: a review.
AB  - BACKGROUND: The Areca catechu Linn. is the fourth most used drug in the world
      after nicotine, ethanol and caffeine. This plant contains nine alkaloids with
      muscarinic and nicotinic action, which could have an antipsychotic effect. AIM:
      The aim of this work is reviewing literature data about the potential action of
      betel alkaloids on positive, negative and cognitive symptoms of schizophrenia.
      METHOD: We reviewed the clinical literature data since 1980 via a PubMed search
      for the terms: arecoline, arecaidine, guvacine, guvacoline, betel, Areca catechu,
      positive and negative symptoms, cognitive symptoms, psychosis and schizophrenia
      in combination. CONCLUSION: Male high consumption of betel had significantly
      lower positive symptoms than low consumers or non-betel users.

PMID- 21859399
TI  - Perhaps it is time to rethink IBS-D.

PMID- 21859400
TI  - Assessment of matrix Gla protein, Klotho gene polymorphisms, and oxidative stress
      in chronic kidney disease.
AB  - Increased vascular calcification and oxidative stress are considered as extra
      renal risk factors at the pathogenesis cardiovascular events in chronic kidney
      disease (CKD). We investigated matrix Gla protein (MGP) (T-138C, Glu60X,
      Thr83Ala) and Klotho (Cys370Ser) gene polymorphisms, serum MGP levels, and
      oxidative stress status of 84 CKD patients and 37 healthy controls. The MGP gene
      Glu60X and Thr83Ala polymorphisms were significantly associated with CKD. The
      correlation between T-138C genotype of MGP gene, Cys370Ser genotype of Klotho
      gene, and CKD was not significant (p > 0.05). At the haplotype analysis, the
      combination of the X allele of Glu60X and the Thr allele of Thr83Ala showed a
      significantly increased risk of CKD (p < 0.05). X allele, Thr allele, and C
      allele of T-138C were associated with diabetes mellitus and CKD phenotypes
      occurring concurrently (p < 0.01). Serum zinc levels were significantly low in
      end-stage renal disease (ESRD) patients (p = 0.0001). The total comet score
      frequency of ESRD patients was higher than that of control group (p < 0.05). The
      urinary 8-hydroxy-2'-deoxyguanosine levels were significantly high in CKD
      patients (p < 0.05). According to this study, analyzing the distribution of MGP
      gene and oxidative stress status would be very informative in order to detect
      their role at CKD.

PMID- 21859401
TI  - Effects of omega-3 fatty acids on serum lipids, lipoprotein (a), and hematologic
      factors in hemodialysis patients.
AB  - BACKGROUND: Lipid abnormalities, especially high serum lipoprotein (a) [Lp (a)]
      concentration, and anemia are two major causes of cardiovascular diseases (CVDs)
      in hemodialysis patients. Therefore, this study was designed to investigate the
      effects of marine omega-3 fatty acids on serum lipids, Lp (a), and hematologic
      factors in hemodialysis patients. METHODS: Thirty-four hemodialysis patients were
      randomly assigned to either omega-3 fatty acid supplement or placebo group.
      Patients in the omega-3 fatty acids group received 2080 mg marine omega-3 fatty
      acids, daily for 10 weeks, whereas the placebo group received a corresponding
      placebo. At baseline and the end of week 10, 7 mL blood was collected after a 12-
      to 14-h fast and serum triglyceride, total cholesterol, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lp (a), blood
      hemoglobin, hematocrit, red blood cells (RBCs), mean corpuscular volume (MCV),
      mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration
      (MCHC) were measured. RESULTS: Serum triglyceride decreased significantly in the
      omega-3 fatty acids group at the end of week 10 compared with baseline (p < 0.05)
      and this reduction was significant in comparison with the placebo group (p <
      0.01). No significant differences were observed between the two groups in mean
      changes of serum total cholesterol, LDL-C, HDL-C, Lp (a), blood hemoglobin,
      hematocrit, RBC, MCV, MCH, and MCHC. CONCLUSION: The results of our study
      indicate that marine omega-3 fatty acids can reduce serum triglyceride, as a risk
      factor for CVD, but it does not affect other serum lipids, Lp (a), and
      hematologic factors in hemodialysis patients.

PMID- 21859402
TI  - Recognition of chronic kidney disease in a general medicine outpatient clinic.
AB  - Chronic kidney disease (CKD) is a major health problem. Recent emphasis has been
      to prevent the progression of CKD. We used chart audits to see if CKD was an
      under-recognized condition in a general medicine resident clinic. Data focused on
      recognition of CKD, 3 or 4, evaluation of metabolic bone disease, and anemia. A
      multifaceted educational initiative was developed and occurred between 2005 and
      2010. Three retrospective chart audits were performed, in 2005 prior to the
      education and again in 2007 and 2010. In 2005, less than one-fifth of patients
      were identified as CKD, 3 or 4. Evaluation of bone disease and anemia is similar.
      Initial results were reviewed with the residents and handouts for metabolic bone
      monitoring were developed. Wall charts of the handouts were also posted. In 2007,
      CKD recognition increased slightly, but more patients had bone disease and anemia
      evaluations. After 2007, the only educational intervention was a CKD lecture
      given yearly. In 2010, the audit saw decreased recognition of CKD and a decline
      in metabolic bone monitoring. Although complete blood count (CBC) monitoring
      decreased, iron studies increased to 50% of patients. We conclude that despite
      educational initiatives and re-enforcement efforts with the internal medicine
      residents and attending staff, major issues related to CKD are not being
      recognized or addressed. With an increasing CKD population, attempts must be made
      to improve recognition and management. Novel strategies need to be developed.

PMID- 21859405
TI  - An evolving integrative treatment program for military sexual trauma (MST) and
      one veteran's experience.
AB  - Military sexual trauma (MST) increases the risk for Posttraumatic Stress Disorder
      (PTSD) and multiple other comorbidities, presenting substantial challenges for
      nurses and psychiatric and medical clinicians. A specialized VA Medical Center
      outpatient program is patterned after Herman's three-phased, empirically
      supported, recovery treatments. We use a case example of a female veteran MST
      survivor to illustrate our treatment model. She presented to our program meeting
      diagnostic criteria for PTSD, Major Depressive Disorder, and a history of
      substance abuse. Post-treatment she demonstrated improved scores on measures of
      PTSD, quality of life, and socialization. This model shows promise for treatment
      of MST survivors with PTSD.

PMID- 21859403
TI  - Balancing between sensitization and repression: the role of opium in the life and
      art of Edgar Allan Poe and Samuel Taylor Coleridge.
AB  - The creative process contains both conscious and unconscious work. Therefore,
      artists have to face their unconscious processes and work with emotional material
      that is difficult to keep under control in the course of artistic creation.
      Bringing these contents of consciousness to the surface needs special sensitivity
      and special control functions while working with them. Considering these
      mechanisms, psychoactive substance can serve a double function in the case of
      artists. On the one hand, chemical substances may enhance the artists'
      sensitivity. On the other hand, they can help moderate the hypersensitivity and
      repress extreme emotions and burdensome contents of consciousness. The authors
      posit how the use of opiates could have influenced the life and creative work of
      Edgar Allan Poe and Samuel Taylor Coleridge.

PMID- 21859406
TI  - Children's view of a major depression affecting a parent in the family.
AB  - This study aims to elucidate, from the children's perspective, the meaning for
      family life of a parent suffering a major depression disorder. Eight children and
      young adults were interviewed. Phenomenological-hermeneutic analysis generated
      two themes: (1) "Being a rescuing observer" with the subthemes, "Being attentive"
      and "Being considerate," and (2) "Being a frustrated observer" with the
      subthemes, "feeling discomfort" and "being out of it." Children's lives alternate
      between responsibility and loneliness as they wait for reciprocity in family life
      to return to normal. Children need support in order to manage their sense of
      responsibility and loneliness adequately.

PMID- 21859407
TI  - Elders' experiences of the death of an adult child.
AB  - The death of a child can result in complicated grief. Thirty-one adults, 60 years
      of age or older, who lost an adult child, participated in a qualitative study
      using a focus group format that allowed them to discuss their experience. A
      hermeneutical approach was used to develop an overall thematic description of
      what it meant to an older person to lose an adult child. Four major themes
      emerged: losses, limited influence/decision making power, regrets, and decreased
      quality of life. Suggested interventions to prevent complicated grief in elders
      who experienced the death of an adult child include attentive listening,
      storytelling, and the use of metaphors.

PMID- 21859408
TI  - A systematic literature review: self-mutilation among adolescents as a phenomenon
      and help for it-what kind of knowledge is lacking?
AB  - The aim of this review article is to present current knowledge of self-mutilation
      among adolescents as a phenomenon and to define what kind of knowledge is lacking
      based on existing literature. The literature searches were executed in the CINAHL
      and Medline databases in 2010. The analysed data consisted of 126 articles and
      inductive content analysis was carried out. Existing knowledge of self-mutilation
      was categorized into the following two classes: (1) self-mutilation as a
      phenomenon and (2) caring for persons who self-mutilate or self-harm.

PMID- 21859409
TI  - Structured reflection on the clinical supervision of supervisees with and without
      a core mental health professional background.
AB  - This paper reflects on particular aspects of the author's supervisory
      relationships. A reflective framework was used to aid the process. The issue
      explored the factors involved when supervising supervisees without a core mental
      health professional background are explored; in particular, the factors of
      accountability and responsibility. To aid reflection, relevant literature was
      explored. Foundational/generic competencies that are typically acquired during
      professional training can be gained in other ways. Supervisors should spend time
      with all supervisees, not just those without a core mental health professional
      background, to learn more about their background, assumptions, and prior
      experiences. Through the reflective process the author learnt how, as a
      supervisor, there needs to be a constant process of learning and adaptation.

PMID- 21859410
TI  - The high prevalence of poor physical health and unhealthy lifestyle behaviours in
      individuals with severe mental illness.
AB  - Recent mental health care policy has addressed the need for health care
      professionals to consider the physical health of consumers. Mental health nurses
      are particularly well-placed for this role. To provide mental health nurses with
      practical information, this narrative review summarises evidence from recent
      research on the physical health of individuals with Serious Mental Illness (SMI).
      In those with SMI, the international prevalence of obesity, the metabolic
      syndrome, diabetes mellitus, symptoms of cardiovascular disease, and respiratory
      disease all exceed that of the general population by at least two times, and HIV
      prevalence may be increased by as much as eight times. This increased prevalence
      of chronic disease may be largely responsible for an increased risk of death of
      up to five times, resulting in as much as 30 years of potential life lost. Of
      particular concern, the recent evidence suggests that for physical health and
      increased mortality, the gap between individuals with SMI and the general
      population is worsening. Unhealthy lifestyle behaviours undoubtedly play a role
      in the development of poor physical health and chronic disease, and the present
      review indicates that low physical activity, poor diet, smoking, alcohol and
      substance abuse, and risky sexual behaviour are common in individuals with SMI.
      This narrative review demonstrates that the prevalence of poor physical health
      and health behaviours in people with SMI far exceed that observed in the general
      population, and reinforces the urgent need for mental health nurses to address
      physical health concerns in patients.

PMID- 21859411
TI  - Benefits of a poetry writing intervention for family caregivers of elders with
      dementia.
AB  - This pilot clinical trial tested effectiveness of a poetry writing intervention
      for family caregivers of elders with dementia. This paper presents findings from
      a larger study using mixed methods to examine outcome variables of self
      transcendence, resilience, depressive symptoms, and subjective caregiver burden.
      Findings reported here focus on qualitative analysis of in-depth interviews
      conducted with participants following their poetry writing experience. A grounded
      theory approach was used. Themes that arose from the data support a mid-range
      theory of self-affirmation in caregivers with subthemes of achievement,
      catharsis, greater acceptance, empathy, self-awareness, reflection, creative and
      fun, positive challenge, and helping others.

PMID- 21859412
TI  - Promoting a culture of tolerance.

PMID- 21859413
TI  - A common language is so basic!

PMID- 21859416
TI  - COPD: moving beyond physiological reductionism.

PMID- 21859417
TI  - Prediction of survival by neutropenia according to delivery schedule of
      oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a
      randomized international trial (EORTC 05963).
AB  - Circadian clocks control cellular proliferation and drug metabolism over the 24
      h. However, circadian chronomodulated chemotherapy with 5-fluorouracil,
      leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared
      with the non-time-stipulated FOLFOX2, in an international randomized trial
      involving patients with previously untreated metastatic colorectal cancer (EORTC
      05963). The authors hypothesized that treatment near maximum tolerated dose could
      disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of
      FOLFOX2. Patients with available data (N = 556) were categorized into three
      subgroups according to the worst grade (G) of neutropenia experienced during
      treatment. Distinct multivariate models with time-dependent covariates were
      constructed for each treatment schedule. Neutropenia incidence (all grades) was
      33% on chronoFLO4 and 61% on FOLFOX2 (p < .0001), and G3-4 were 7% and 25%,
      respectively (p < .0001). Neutropenia was significantly more frequent in women
      than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median
      survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in
      neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7
      and 19.4 mo, respectively, on chronoFLO4 (p = .36). Multivariate analysis
      confirmed occurrence of severe neutropenia independently predicted for better
      overall survival on FOLFOX2 (HR = 0.56; p = .015), and worse survival on
      chronoFLO4 (HR = 1.77, p = .06), with a significant interaction test (p < .0001).
      Prediction of better survival in neutropenic patients on FOLFOX2 supports the
      administration of conventional chemotherapy near maximum tolerated dose. The
      opposite trend shown here for chronoFLO4 supports the novel concept of jointly
      optimized hematologic tolerability and efficacy through personalized circadian
      timed therapy.

PMID- 21859418
TI  - Salivary melatonin rhythm as a marker of the circadian system in healthy children
      and those with attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder of childhood. Problems with sleep structure, efficiency,
      and timing have been reported in some, but not all, studies on ADHD children. As
      the sleep-wake cycle belongs to circadian rhythms, the timekeeping circadian
      system might be involved in ADHD. To assess whether the circadian system of ADHD
      children differs from that of controls, the rhythm of the pineal hormone
      melatonin was used as a reliable marker of the system. Saliva from 34 ADHD and 43
      control 6- to 12-yr-old children was sampled at 2-h intervals throughout the
      entire 24-h cycle, and the melatonin profiles of the ADHD and control children
      were compared. The nocturnal melatonin peaks of the ADHD and control group did
      not differ significantly. The high nocturnal interindividual variability of the
      peaks seen in adulthood was present already in the studied children. The 24-h
      melatonin profiles of all the ADHD subjects did not differ significantly from
      those of the control subjects. Categorization of subjects according to age, into
      groups of 6- to 7-yr-old (9 ADHD, 5 control), 8- to 9-yr-old (16 ADHD, 26
      control), and 10- to 12-yr-old (9 ADHD, 12 control) children, revealed
      significant differences between the ADHD and control group in the melatonin
      rhythm waveform, but not in nocturnal melatonin peaks; the peaks were about the
      same in both groups and did not change significantly with increasing age. In the
      oldest, but not in the younger, children, the melatonin signal duration in the
      ADHD group was shorter than in the control group. The difference might be due to
      the fact that whereas in the control group both the evening melatonin onset and
      the morning offset phase delayed in the oldest children relative to those in the
      youngest children, in the ADHD group only the onset, but not the offset, phase
      delayed with increasing age. The data may indicate subtle differences between the
      circadian system of ADHD and control children during development.

PMID- 21859419
TI  - Evaluating the population with intellectual disability unable to comply with
      routine dental treatment using the International Classification of Functioning,
      Disability and Health.
AB  - PURPOSE:  The aim of this study was to investigate the use of general anaesthesia
      (GA) among patients with intellectual disability (ID) in relation to the
      International Classification of Functioning (ICF). METHOD:  Twenty-seven ICF
      codes related to the tolerance of the dental treatment were chosen. The sample
      consisted of 100 children with ID divided into two groups (50 patients in whom
      routine dental treatment had been accomplished and 50 patients who had been
      treated under GA). Differences between the groups were analysed using the chi
      square test, bivariate correlation and multiple logistic regression analysis.
      RESULTS: The GA group showed higher levels with regard to the following codes:
      b117--intellectual function, b2801--pain in head and neck, d310--communication,
      d530--toileting, d540--dressing, e310--immediate family, e5400--transportation
      services and e5850--education and training services. The severity of ID
      significantly correlated with the 'Activities and Participation' codes. Three
      predictors of GA treatment were identified: 'Pain in head and neck' (p < 0.001),
      'Transportation services, systems and policies' (p < 0.05) and 'Education and
      training services, systems and policies' (p < 0.05). CONCLUSIONS: The use of GA
      increases with the severity of ID. Acute and painful conditions result in more
      frequent use of GA. Unfavourable environmental factors present barrier to routine
      dental management.

PMID- 21859420
TI  - Involvement in volunteering: an exploration of the personal experience of people
      with aphasia.
AB  - This article reports results from a qualitative study in the U.K. of people with
      aphasia who have been involved in volunteering. The study describes their
      experiences; explores, from their perspective, the effects of involvement; and
      identifies key facilitators and barriers to the successful participation of
      people with aphasia in community activity. Data were collected by means of 10
      individual semi-structured interviews using supported conversation techniques and
      through a focus group involving five more people. All participants had aphasia
      following a stroke. Average length of time since stroke for participants in the
      individual interviews was 5.6 years (range 3-12 years) and for participants in
      the focus group was 4.6 (range 1-10 years). Results are discussed according to
      four themes: (i) the effects of the activity on self; (ii) the effects on others;
      (iii) the effects on organisations hosting the activity and (iv) perceived
      barriers and facilitators impacting on volunteering. Implications are drawn for
      the promotion of participatory community activity within the matrix of
      therapeutic approaches and considered in light of previous studies that have
      reported the conceptualisations of people with aphasia about their lives and
      aspirations.

PMID- 21859421
TI  - Patients' perceptions of the treatment and management of hand osteoarthritis: a
      focus group enquiry.
AB  - PURPOSE:  Osteoarthritis (OA) is the commonest reason for a musculoskeletal
      consultation in primary care in older adults. There is evidence that appropriate
      advice and management is sub-optimal. The aim of this study was to explore
      perceptions and experiences of the treatment and management of hand OA in older
      adults. METHODS:  Four focus groups were conducted with primary (n = 15) and
      secondary (n = 14) care participants aged 50-84 years (mean age 64.9 years; 3
      males, 14 females) with a clinical diagnosis of hand OA. Data were tape-recorded,
      transcribed and analysed using thematic analysis and constant comparison method.
      RESULTS:  Participants described a lack of help and information with regards to
      management of their hand OA and also a perceived lack of understanding of the
      impact of hand OA on the individual. Some received contradictory advice about its
      management. Beliefs about treatment efficacy were balanced against perceived and
      actual side-effects and tolerance, and such perceptions appeared to influence the
      use of alternative therapies. CONCLUSIONS:  The study identified a perceived
      unmet need in people with hand OA presenting in primary and secondary care. This
      may be due to the clinical uncertainty of treatment, lack of high-quality
      randomised controlled trials evaluating therapeutic options, and the limited
      written information available incorporating the patient experience. The study
      emphasised the need to understand patient illness and treatment beliefs. A better
      understanding of illness and treatment beliefs will facilitate the use of
      evidence-based approaches in the management of hand OA.

PMID- 21859423
TI  - Salivary markers of oxidative stress and Salivette collection systems.
AB  - BACKGROUND: Biomarkers of oxidative stress can be measured in saliva and
      represent a promising tool for the research of oral diseases. Saliva sampling and
      further processing has been improved by Salivette collection systems. The aim of
      this study was to analyze the effects of two different Salivette collection
      systems on salivary biomarkers of oxidative stress in comparison to whole
      unstimulated saliva. METHODS: Whole unstimulated saliva and saliva samples
      collected using cotton and polypropylene Salivette collection systems were
      obtained from 20 young healthy volunteers (aged 20-30 years). Advanced glycation
      end products (AGEs), advanced oxidation protein products (AOPP), thiobarbituric
      acid reacting substances (TBARS), ferric reducing ability of saliva and total
      antioxidant capacity were measured. RESULTS: In samples collected using the
      cotton Salivette, higher AGEs and TBARS concentrations (by 97% and 2036%) were
      determined. In samples collected using the polypropylene Salivette cortisol,
      cortisol AOPP concentrations were lower (by 60%) in comparison to measurements in
      whole unstimulated saliva. Markers of antioxidant status were comparable in all
      types of samples. CONCLUSIONS: Salivette and Salivette cortisol collection
      systems significantly altered the determined concentrations of several markers of
      oxidative stress in comparison to measurements in whole unstimulated saliva
      samples.

PMID- 21859424
TI  - Phenotype of Gc-globulin influences the macrophage activating factor (MAF) levels
      in serum.
AB  - BACKGROUND: Gc-globulin is a polymorphic protein with three phenotypes: Gc 1-1,
      Gc 2-1 and Gc 2-2. Deglycosylation of Gc-globulin results in a Gc-macrophage
      activating factor (Gc-MAF). This study investigated the potential of MAF as a
      tumour marker and the influence of Gc-phenotypes on serum MAF-concentrations.
      METHODS: Gc-phenotype of 98 healthy individuals and 60 cancer patients was
      determined. MAF-levels of healthy individuals and cancer patients were analysed
      according to their Gc-phenotype using a Helix pomatia agglutinin-based ELISA. ROC
      curves analysed the efficiency of MAF as a tumour marker. RESULTS: MAF-levels
      between controls and patients were significantly different (p<0.001). No
      phenotypic differences were found in the patients. In comparison with the
      controls, MAF-values were significantly lower in cancer patients carrying Gc 1-1
      (p<0.01) and Gc 2-1 (p<0.001). No difference was observed in Gc 2-2 phenotype.
      Diagnostic accuracy of MAF as a tumour marker also demonstrated pronounced
      differences between Gc-phenotypes. CONCLUSIONS: Gc-phenotype is a confounding
      factor when interpreting MAF-data. The value of MAF as a tumour marker varies
      according to phenotype. Future studies on MAF will have to consider the effect of
      Gc-phenotype.

PMID- 21859425
TI  - Novel anti-diabetic effect of SCM-198 via inhibiting the hepatic NF-kappaB
      pathway in db/db mice.
AB  - There are reports of early evidence that suggest the involvement of chronic low
      grade inflammation in the pathogenesis of Type 2 diabetes. Thus, substances that
      have effects in reducing inflammation could be potential drugs for Type 2
      diabetes. Leonurine (4-guanidino-n-butyl syringate; SCM-198) is an alkaloid in HL
      (Herba leonuri), which was reported to possess anti-inflammatory properties. We
      hypothesize that SCM-198 may have beneficial effects on Type 2 diabetes. In the
      present study, we attempted to test this hypothesis by evaluating the anti
      diabetic effect of SCM-198 and the possible underlying mechanisms of its effects
      in db/db mice. SCM-198 (50, 100 and 200 mg/kg of body weight), pioglitazone (50
      mg/kg of body weight, as a positive control) or 1% CMC-Na (sodium
      carboxymethylcellulose) were administered to the db/db or db/m mice once daily
      for 3 weeks. After 3 weeks, SCM-198 (200 mg/kg of body weight) treatment
      significantly reduced the fasting blood glucose level and increased the plasma
      insulin concentration in the db/db mice, meanwhile it significantly lowered the
      plasma TAG (triacylglycerol) concentration and increased the HDL (high-density
      lipoprotein)-cholesterol concentration. Moreover, the dysregulated transcription
      of the hepatic glucose metabolic enzymes, including GK (glucokinase), G6Pase
      (glucose-6-phosphatase) and PEPCK (phosphoenolpyruvate carboxykinase), was
      recovered by an Akt-dependent pathway. The pro-inflammatory mediators {such as
      TNFalpha (tumour necrosis factor alpha), IL (interleukin)-6, IL-1beta,
      degradation of IkappaB [inhibitor of NF-kappaB (nuclear factor-kappaB)] alpha and
      thereafter activation of NF-kappaB} were reversed by SCM-198 treatment in the
      db/db mice. The present study provides first evidence that SCM-198 exhibits anti
      inflammatory activity and has an ameliorating effect on diabetic symptoms via
      inhibiting of NF-kappaB/IKK (IkappaB kinase) pathway. Consequently, we suggest
      that SCM-198 may be a prospective agent for prevention and/or moderation of the
      progress of Type 2 diabetes.

PMID- 21859426
TI  - Two novel HLA-A alleles, A*29:02:01:02 and A*68:01:01:02, were identified by
      genomic full-length cloning and sequencing.
AB  - Two novel HLA-A alleles differing from their closest related alleles by
      nucleotide exchanges in introns, A*29:02:01:02 and A*68:01:01:02, were
      identified.

PMID- 21859427
TI  - A novel HLA-B*40 allele, HLA-B*40:74, detected in a Chinese individual.
AB  - The HLA-B*40:74 allele has two nucleotide changes at positions 103 and 106 of
      exon 2 from the closest matching allele HLA-B*40:01:01.

PMID- 21859428
TI  - Full-length sequence of a novel HLA-A*02:230 allele.
AB  - The full-length sequences of exons 1-8 of this novel HLA-A*02:230 allele are
      identical to those of HLA-A*02:03:01, except for one nucleotide change at nt 858
      in exon 3 from G to A.

PMID- 21859429
TI  - Full-length sequence of a novel HLA-B*15:220 allele identified in an individual
      from Guadeloupe.
AB  - The new HLA-B*15:220 allele shows a single-nucleotide substitution in exon 1 at
      position 47 (C>T) when compared to its closest allele HLA-B*15:03:01, resulting
      in an amino acid substitution from Ala to Val in the signal peptide at codon -9.

PMID- 21859430
TI  - Clonal and lineage analysis of somatic DNMT3A and JAK2 mutations in a chronic
      phase polycythemia vera patient.

PMID- 21859431
TI  - New topics in bradykinin research.
AB  - Bradykinin has been implicated to contribute to allergic inflammation and the
      pathogenesis of allergic conditions. It binds to endothelial B(1) and B(2)
      receptors and exerts potent pharmacological and physiological effects, notably,
      decreased blood pressure, increased vascular permeability and the promotion of
      classical symptoms of inflammation such as vasodilation, hyperthermia, oedema and
      pain. Towards potential clinical benefit, bradykinin has also been shown to exert
      potent antithrombogenic, antiproliferative and antifibrogenic effects. The
      development of pharmacologically active substances, such as bradykinin receptor
      blockers, opens up new therapeutic options that require further research into
      bradykinin. This review presents current understanding surrounding the role of
      bradykinin in nonallergic angioedema and other conditions seen by allergists and
      emergency physicians, and its potential role as a therapeutic target.

PMID- 21859432
TI  - Effects of muscarinic receptor antagonists on acetylcholine-induced contractions
      of jejunal smooth muscle in horses.
AB  - This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and
      3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on
      acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of
      horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2)
      and 5% CO(2), and the developed tension in response to Ach was recorded before
      and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M),
      pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When
      competitive antagonism was characterized, the affinity constant (pA(2)) was
      calculated by Schild plots. A parallel rightward shift in the concentration
      response curves was observed after 4-DAMP and pirenzepine. Methoctramine
      presented a dual effect on the concentration-response curves: lower
      concentrations induced a parallel rightward shift without altering the maximum
      intensity of contraction (E(max)), while the highest concentration increased
      slope of the concentration-response curve and increased E(max). The pA(2) for 4
      DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced
      contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3)
      receptors. The complex role of M(2) receptors in jejunal smooth muscle
      contractions was evident because methoctramine potentiated the contractile
      response to higher doses of Ach.

PMID- 21859433
TI  - The effects of hyperosmosis or high pH on a dual-species biofilm of Enterococcus
      faecalis and Pseudomonas aeruginosa: an in vitro study.
AB  - AIM: To investigate the effect of hyperosmotic hyperosmosis or alkaline stress on
      a dual-species biofilm of Enterococcus faecalis and Pseudomonas aeruginosa.
      METHODOLOGY: Biofilms were grown on glass cover slips suspended in bacterial
      inoculate for 96 h, after which the cover slips with attached biofilms were
      immersed in brain heart infusion broth (BHI-broth) with 6 mol L(-1) sodium
      chloride (NaCl) representing the hyperosmotic group or Ca(OH)(2), pH 12.1,
      representing the alkaline group. Two per cent sodium hypochlorite and BHI- broth
      served as positive and negative controls, respectively. After treatment, the
      biofilms were washed, harvested and plated on blood-agar plates after serial
      dilution. The bactericidal effect was assessed by determining the colony-forming
      units (CFU). The effect on the biofilm mass was imaged with confocal laser
      scanning microscopy (CLSM). RESULTS: Hyperosmosis reduced the CFU of both species
      significantly after 72 h (P < 0.0001). After 168 h, P. aeruginosa was eradicated
      and the E. faecalis reduction was more than 99%. High pH could not induce a
      significant bacterial reduction. CLSM revealed dense flocculation of the biofilms
      incubated in alkaline broth. CONCLUSION: Hyperosmosis effectively reduced a dual
      species biofilm of E. faecalis and P. aeruginosa, whilst high pH had limited
      bactericidal effect in this model.

PMID- 21859434
TI  - Impact of caregiving on Finnish family caregivers.
AB  - BACKGROUND: Numerous studies have examined the caregiver burden that family
      caregivers often experience. However, caregiving situations may also include
      positive elements that have recently received greater research attention. AIM:
      The aim was to examine the positive value and negative impact of caregiving for
      the family caregiver. METHOD: Caregiving experience was measured with the
      modified 15-item Carers of Older People in Europe Index. Surveys were completed
      by family caregivers at the baseline and after 6 months. RESULTS: At the
      baseline, most family caregivers thought that caregiving was worthwhile, had a
      good relationship with the person they cared for and coped well as a caregiver.
      Fifty-five per cent of the respondents did not feel trapped in their caregiver
      role, though a third did, and a majority found caregiving to be too demanding.
      Most perceived themselves to be supported by their family, while 40% did not feel
      supported by health and social services. During the 6-month study period, the
      negative impact score declined, and the scores for positive value and quality of
      support improved. The care recipient's management at home (p < 0.001) was the
      single best predictor of the negative impact on the family caregiver; the family
      caregiver's older age (p < 0.01) best predicted the quality of support; and the
      family caregiver's good relationship with the care recipient (p < 0.01) best
      predicted the positive value of caregiving. CONCLUSIONS: The study indicated that
      even if the health status of the care recipient dramatically worsened, the family
      caregiver's experiences of caregiving became more positive. This is because
      family caregiving was perceived to be worthwhile, most family caregivers had a
      close relationship with the person they cared for and they received support from
      their family. Interventions that focus on family caregivers' positive experiences
      of caregiving would be important in protecting them from the negative
      consequences of caregiving.

PMID- 21859435
TI  - Detrimental effects of divalproex on warfarin therapy following mechanical valve
      replacement.
AB  - Drug interaction between Warfarin and psychiatric agents may have important
      therapeutic effects for patients undergoing cardiac surgery. We present a case of
      a patient in whom concurrent treatment with Warfarin and valproic acid resulted
      in supratherapeutic international normalized ratio values. A discussion of the
      possible mechanisms for this interaction as well as a review of interactions
      between Warfarin and other psychiatric medications is the subject of this case
      report.

PMID- 21859436
TI  - A close relationship between type 1 diabetes and vitamin A-deficiency and matrix
      metalloproteinase and hyaluronidase activities in skin tissues.
AB  - Numerous wrinkles are observed in the skin of streptozotocin (STZ)-induced type 1
      diabetic rats, which are similar to those seen in vitamin A-deficient (VAD) rats.
      Retinoic acid (RA), the active form of vitamin A, promotes the production of
      collagen in dermis and induces cell growth and inhibition of epidermal
      differentiation in skin tissues. Normal skin function is maintained by the
      extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinase (MMP) and
      hyaluronidase (HAase). This study is the first comparison of MMP and HAase
      activities in skin tissues of type 1 diabetic, VAD and RA-treated animal models.
      In skin tissues of type 1 diabetic and VAD rats or VAD mice, both MMP-2 and HAase
      activities increased as compared with controls. In contrast, MMP and HAase
      activities were reduced in the skin tissues of RA-treated mice. Blood retinol
      levels in type 1 diabetic rats were lower than controls. These results indicate a
      close relationship between type 1 diabetes and vitamin A-deficiency on MMP and
      HAase in skin tissues, suggesting that type 1 diabetic rats could be vitamin A
      deficient. Vitamin A-derived RA might be a significant regulator of ECM-degrading
      enzyme expression and diabetic symptoms.

PMID- 21859437
TI  - Identification of the sites of action of SrmB, a DEAD-box RNA helicase involved
      in Escherichia coli ribosome assembly.
AB  - DEAD-box RNA-dependent ATPases are ubiquitous enzymes that participate in nearly
      all processes involving RNA, but their detailed molecular functions remain
      generally unknown. SrmB, one of the five Escherichia coli DEAD-box proteins,
      participates in the assembly of the large ribosomal subunit notably by
      facilitating the incorporation of L13, one of the ribosomal proteins that bind
      23S rRNA earliest. Previously, we showed that SrmB is tethered to nascent
      ribosome through interactions with L4, L24 and the region from domain I of 23S
      rRNA that binds them. To identify the sites of action of SrmB, we have
      characterized rRNA mutations that bypass SrmB requirement. Five of them affect
      the same position from two repeated heptanucleotides in domain II of 23S rRNA,
      whereas two others affect a complementary hexanucleotide in 5S rRNA. Thus the
      sites of action of SrmB differ from its tethering site. In the mature ribosome,
      one of the heptanucleotides participates in a highly compact structure that
      contacts L13, the '1024 G-ribo wrench'. In addition, we have observed that the
      assembly defect of DeltasrmB cells worsens as rRNA synthesis increases. Based on
      these results, we propose two non-exclusive scenarios for the role of SrmB in
      ribosome assembly.

PMID- 21859438
TI  - Validation of an automated wireless system to monitor sleep in healthy adults.
AB  - The availability of a reliable system to record sleep stage measures easily and
      automatically in ambulatory settings could be of utility for research and
      clinical work. The aim of this study was to evaluate a novel wireless system (WS)
      that does not require skilled preparation for the automatic collection and
      scoring of human sleep. Twenty-nine healthy adults underwent concurrent sleep
      measurement via the WS, polysomnography (PSG) and an actigraph (ACT) in a sleep
      laboratory for one assessment night preceded by an acclimation night. The PSG
      recordings were scored by two experienced trained technicians from separate
      laboratories. Each recording was scored by both technicians to Rechtschaffen and
      Kales (R&K) criteria. The WS and ACT were compared with each of the PSG scores
      and a consensus PSG score, and the PSG scores were compared with each other.
      Inter-rater agreement was assessed for each pair over all pooled epochs by
      percentage agreement, Cohen's kappa and intraclass correlation coefficient. The
      WS agreement with each of the two PSG scores for sleep stages was 75.8 and 74.7%,
      respectively. WS agreement with each of the two PSG scores for sleep/wakefulness
      was 92.6 and 91.1%, ACT agreement with PSG was 86.3 and 85.7%. The PSG scorers'
      agreement with each other for sleep stages was 83.2%, and for sleep/wakefulness
      was 95.8%. The findings from the current study indicate that the WS may provide
      an easy to use and accurate complement to other established technologies for
      measuring sleep in healthy adults.

PMID- 21859439
TI  - Costs of interventions for AIDS orphans and vulnerable children.
AB  - OBJECTIVE: To review the published and grey literature for information regarding
      the costs and cost-effectiveness of interventions aimed at improving the welfare
      of orphans and vulnerable children owing to HIV/AIDS in low- and middle-income
      countries. METHOD: We carried out a search of the peer-reviewed literature
      through PubMed, EconLit, and Web of Science for the period January 2000 to
      December 2010. We also extensively reviewed the grey literature through
      generalized web searches and consultations with experts and searches of the web
      pages of the main organizations active in providing services to orphans and
      vulnerable children (OVC). The search yielded 216 articles; cross-sectional or
      longitudinal studies and articles that did not address specific interventions
      were not considered. The remaining 21 articles were categorized by domain and by
      type of intervention strategy. RESULTS: All studies reviewed were carried out in
      sub-Saharan Africa. All outcomes are expressed as cost per child per year (in
      2010 USD). Foster care estimates range from $614 to $1921. Educational support
      for primary school ranged from $30 to $75. Health interventions that would ensure
      child survival can be delivered for about $55. CONCLUSION: More research is
      needed to improve planning and delivery of interventions for OVC. The paucity of
      cost and cost-effectiveness data reflects the limited number of effectiveness
      studies. Nevertheless, this systematic literature review shows evidence that
      suggests that in the area of housing, foster care appears to be more cost
      effective than institutional care (orphanages).

PMID- 21859440
TI  - Access to, use of and satisfaction with health services among adults enrolled in
      Brazil's Family Health Strategy: evidence from the 2008 National Household
      Survey.
AB  - OBJECTIVE: To assess the effects of participation in Brazil's primary healthcare
      programme (the Family Health Strategy or FHS) on access, use and satisfaction
      with health services among adults. METHODS: Data are from the 2008 National
      Household Survey (PNAD) on 264 754 adults. This cross-sectional analysis compares
      FHS enrollees to both non-enrollees and those with private health plans. We
      calculated predicted probabilities of each outcome stratified by household wealth
      quintile, rural/urban location and sex using robust Poisson regression. We
      performed propensity score analysis to assess the differences in access among FHS
      enrollees and the rest of the population, once relevant socio-demographic
      characteristics and other determinants of access were balanced. RESULTS: Compared
      to families with neither FHS enrolment nor private health plans, adult FHS
      enrollees were generally more likely to have a usual source of care, to have
      visited a doctor or dentist in the past 12 months, to have access to needed
      medications and to be satisfied with the care they received. The FHS effect was
      largest among urban dwellers and the poorest. CONCLUSIONS: The FHS appears to be
      associated with enhanced access to and utilization of health services in Brazil.
      However, it has not yet been able to match levels of access experienced by those
      with private health plans, perhaps because the population served by the FHS is
      among the poorest, most rural and least healthy in the country.

PMID- 21859441
TI  - Burial surveillance detected significant reduction in HIV--related deaths in
      Addis Ababa, Ethiopia.
AB  - OBJECTIVE: To determine the level of HIV-related mortality reduction after the
      introduction of large-scale antiretroviral therapy (ART) using a burial
      surveillance system coupled with verbal autopsy (VA) in Addis Ababa, Ethiopia.
      METHODS: Prospective burial surveillance was established in 2001 at cemeteries in
      Addis Ababa. VA interviews were periodically conducted on a random sample of
      adult burials registered between 2001 and 2009. Independent physicians reviewed
      the completed VA questionnaires and assigned underlying causes of death. The
      period before 2005 was defined as pre-ART and that since 2005 as the ART era. HIV
      specific mortality fractions were calculated by age, sex and year of burial to
      examine the mortality trends before and during the ART era. RESULTS: Of the 4239
      VA physician diagnoses, 1087 (25.6%) were ascribed to HIV-related deaths. HIV
      related deaths in 2009 were 33% fewer than in 2001. The proportion of HIV-related
      deaths was reduced from 44.0% in the pre-ART period to 20.0% in the ART era.
      Mortality in women (36.7%) declined more than in men (30%). A marked reduction in
      HIV-specific mortality was observed in the age group 30-39 years (from 69.1% pre
      ART to 46.8% during ART era) compared to 20-29 (from 60.5% pre-ART to 41.0%
      during ART) and 40-49 year olds (49.7%) pre-ART to 34.4% during ART provision).
      CONCLUSION: Burial surveillance combined with VA demonstrated a significant
      reduction in HIV-related deaths during the provision of free ART. Replication of
      burial surveillance is recommended in similar settings, where a vital
      registration system is non-existent, to track large-scale population-level
      interventions.

PMID- 21859442
TI  - A pilot study: are dental hygienists in Texas ready for the elderly population
      explosion?
AB  - PURPOSE: At the beginning of the 20th century, people 65 and older comprised 4.1%
      of the population. By the year 2030, it is estimated that people 65 and older,
      the 'Baby Boomer' generation, will comprise more than 20% of the population. This
      will have a profound effect on the practice of dentistry and on society as a
      whole. The purpose of this study was to determine whether dental hygienists in
      Texas felt prepared and willing to treat the elderly in alternative practice
      settings such as nursing homes. METHODS: After institutional review board
      approval, a questionnaire was mailed to 500 hygienists. A 5% systematic sample of
      dental hygiene graduates was taken from four dental hygiene schools in Texas,
      United States of America (USA). Of these, 175 were returned for a 35% response
      rate. Questions asked were degree held, how prepared the participants felt to
      treat the special needs of the elderly, if participants were willing to work in
      alternative practice settings such as a nursing home and if they felt additional
      education was needed. Frequency distributions, correlations and chi square were
      used to analyse the data. RESULTS: Results revealed 86.5% of the respondents felt
      prepared to somewhat prepared to treat the special needs of the elderly based on
      education; equally, 86.5% felt more education was needed to better prepare them
      to treat the elderly. Over half of the respondents would not be willing to work
      in alternative practice settings such as nursing homes. CONCLUSION: The average
      respondents do not feel fully prepared to treat the elderly with special needs,
      and they think more education is needed to better prepare them to treat this
      important target population.

PMID- 21859443
TI  - Genome sequencing reveals diversification of virulence factor content and
      possible host adaptation in distinct subpopulations of Salmonella enterica.
AB  - BACKGROUND: Divergence of bacterial populations into distinct subpopulations is
      often the result of ecological isolation. While some studies have suggested the
      existence of Salmonella enterica subsp. enterica subclades, evidence for these
      subdivisions has been ambiguous. Here we used a comparative genomics approach to
      define the population structure of Salmonella enterica subsp. enterica, and
      identify clade-specific genes that may be the result of ecological
      specialization. RESULTS: Multi-locus sequence analysis (MLSA) and single
      nucleotide polymorphisms (SNPs) data for 16 newly sequenced and 30 publicly
      available genomes showed an unambiguous subdivision of S. enterica subsp.
      enterica into at least two subpopulations, which we refer to as clade A and clade
      B. Clade B strains contain several clade-specific genes or operons, including a
      beta-glucuronidase operon, a S-fimbrial operon, and cell surface related genes,
      which strongly suggests niche specialization of this subpopulation. An additional
      set of 123 isolates was assigned to clades A and B by using qPCR assays targeting
      subpopulation-specific SNPs and genes of interest. Among 98 serovars examined,
      approximately 20% belonged to clade B. All clade B isolates contained two
      pathogenicity related genomic islands, SPI-18 and a cytolethal distending toxin
      islet; a combination of these two islands was previously thought to be exclusive
      to serovars Typhi and Paratyphi A. Presence of beta-glucuronidase in clade B
      isolates specifically suggests an adaptation of this clade to the vertebrate
      gastrointestinal environment. CONCLUSIONS: S. enterica subsp. enterica consists
      of at least two subpopulations that differ specifically in genes involved in host
      and tissue tropism, utilization of host specific carbon and nitrogen sources and
      are therefore likely to differ in ecology and transmission characteristics.

PMID- 21859444
TI  - The appearance of renal cells cytoplasmic degeneration and nuclear destruction
      might be an indication of GNPs toxicity.
AB  - BACKGROUND: Advances in nanotechnology have identified promising candidates for
      many biological and biomedical applications. Since the properties of
      nanoparticles (NPs) differ from that of their bulk materials, they are being
      increasingly exploited for medical uses and other industrial applications. The
      histological and the histochemical alterations in the renal tissues due to gold
      nanoparticles (GNPs) have not well documented and have not yet been identified.
      The aim of the present study was to investigate the particle-size effect of GNPs
      on the renal tissue in an attempt to address their potential toxicity. METHODS: A
      total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or
      100 MUl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days) to
      investigate particle-size effect of GNPs on the renal tissue. Animals were
      randomly divided into groups, 6 GNPs-treated rats groups and one control group.
      Groups 1, 2 and 3 received infusion of 50 MUl GNPs of size 10 nm (3 or 7 days),
      size 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively; while groups 4, 5
      and 6 received infusion of 100 MUl GNPs of size 10 nm, size 20 nm and 50 nm,
      respectively. RESULTS: The histological alterations were mainly seen in the
      cortex and the proximal renal convoluted tubules were more affected than the
      distal ones. In comparison with respective control rats, exposure to GNPs doses
      has produced the following renal tubular alterations: cloudy swelling and renal
      tubular necrosis. Interstitial alterations included: intertubular blood
      capillaries dilatation, intertubular hemorrhage and inflammatory cell
      infiltrations. The glomeruli showed moderate congestion with no hypercelluraity
      and mesangial proliferation or basement membrane thickening. CONCLUSIONS: The
      induced histological alterations might be an indication of injured renal tubules
      due to GNPs toxicity that become unable to deal with the accumulated residues
      resulting from metabolic and structural disturbances caused by these NPs. These
      alterations were size-dependent with smaller ones induced more effects and
      related with time exposure of GNPs. The produced histological alterations may
      suggest that GNPs interact with proteins and enzymes of the renal tissue
      interfering with the antioxidant defense mechanism and leading to reactive oxygen
      species (ROS) generation which in turn may induce stress in the renal cells to
      undergo atrophy and necrosis. More histomorphologcal investigations are needed to
      address the potential threat of GNPs as a therapeutic and diagnostic tool.

PMID- 21859445
TI  - A systematic review and meta-analysis of neurological soft signs in relatives of
      people with schizophrenia.
AB  - BACKGROUND: Neurological soft signs are subtle but observable impairments in
      motor and sensory functions that are not localized to a specific area of the
      brain. Neurological soft signs are common in schizophrenia. It has been
      established that soft signs meet two of five criteria for an endophenotype,
      namely: association with the illness, and state independence. This review
      investigated whether soft signs met a further criterion for an endophenotype,
      namely familial association. It was hypothesized that if familial association
      were present then neurological soft signs would be: (a) more common in first
      degree relatives of people with schizophrenia than in controls; and (b) more
      common in people with schizophrenia than in their first-degree relatives. METHOD:
      A systematic search identified potentially eligible studies in the EMBASE (1980
      2011), OVID - MEDLINE (1950-2011) and PsycINFO (1806-2011) databases. Studies
      were included if they carried out a three-way comparison of levels of soft signs
      between people with schizophrenia, their first-degree relatives, and normal
      controls. Data were extracted independently by two reviewers and cross-checked by
      double entry. RESULTS: After screening 8678 abstracts, seven studies with 1553
      participants were identified. Neurological soft signs were significantly more
      common in first-degree relatives of people with schizophrenia than in controls
      (pooled standardised mean difference (SMD) 1.24, 95% confidence interval (c.i)
      0.59-1.89). Neurological soft signs were also significantly more common in people
      with schizophrenia than in their first-degree relatives (SMD 0.92, 95% c.i 0.64
      1.20). Sensitivity analyses examining the effects of age and group blinding did
      not significantly alter the main findings. CONCLUSIONS: Both hypotheses were
      confirmed, suggesting that the distribution of neurological soft signs in people
      with schizophrenia and their first-degree relatives is consistent with the
      endophenotype criterion of familial association.

PMID- 21859446
TI  - Subunit-specific mutational analysis of residue N348 in HIV-1 reverse
      transcriptase.
AB  - BACKGROUND: N348I in HIV-1 reverse transcriptase (RT) confers resistance to
      zidovudine (AZT) and nevirapine. Biochemical studies demonstrated that N348I
      indirectly increases AZT resistance by decreasing the frequency of secondary
      ribonuclease H (RNase H) cleavages that reduce the RNA/DNA duplex length of the
      template/primer (T/P) and diminish the efficiency of AZT-monophosphate (MP)
      excision. By contrast, there is some discrepancy in the literature in regard to
      the mechanisms associated with nevirapine resistance: one study suggested that it
      is due to decreased inhibitor binding while others suggest that it may be related
      to the decreased RNase H cleavage phenotype. From a structural perspective, N348
      in both subunits of RT resides distal to the enzyme's active sites, to the T/P
      binding tract and to the nevirapine-binding pocket. As such, the structural
      mechanisms associated with the resistance phenotypes are not known. RESULTS:
      Using a novel modelled structure of RT in complex with an RNA/DNA T/P, we
      identified a putative interaction between the beta14-beta15 loop in the p51
      subunit of RT and the RNA template. Substitution of the asparagine at codon 348
      in the p51 subunit with either isoleucine or leucine abrogated the observed
      protein-RNA interaction, thus, providing a possible explanation for the decreased
      RNase H phenotype. By contrast, alanine or glutamine substitutions exerted no
      effect. To validate this model, we introduced the N348I, N348L, N348A and N348Q
      mutations into RT and purified enzymes that contained subunit-specific mutations.
      N348I and N348L significantly decreased the frequency of secondary RNase H
      cleavages and increased the enzyme's ability to excise AZT-MP. As predicted by
      the modelling, this phenotype was due to the mutation in the p51 subunit of RT.
      By contrast, the N348A and N348Q RTs exhibited RNase H cleavage profiles and AZT
      MP excision activities similar to the wild-type enzyme. All N348 mutant RTs
      exhibited decreased nevirapine susceptibility, although the N348I and N348L
      mutations conferred higher fold resistance values compared to N348A and N348Q.
      Nevirapine resistance was also largely due to the mutation present in the p51
      subunit of RT. CONCLUSIONS: This study demonstrates that N348I-mediated AZT and
      nevirapine resistance is due to the mutation in the p51 subunit of RT.

PMID- 21859447
TI  - Asymmetric reproductive isolation between terminal forms of the salamander ring
      species Ensatina eschscholtzii revealed by fine-scale genetic analysis of a
      hybrid zone.
AB  - BACKGROUND: Ring species, exemplified by salamanders of the Ensatina
      eschscholtzii complex, represent a special window into the speciation process
      because they allow the history of species formation to be traced back in time
      through the geographically differentiated forms connecting the two terminal forms
      of the ring. Of particular interest is the nature and extent of reproductive
      isolation between the geographically terminal forms, in this case E. e.
      eschscholtzii and E. e. klauberi. Previous studies have documented infrequent
      hybridization at the end of the ring. Here, we report the first fine-scale
      genetic analysis of a hybrid zone between the terminal forms in southern
      California using individual-based Bayesian analyses of multilocus genetic data to
      estimate levels and direction of hybridization and maximum-likelihood analysis of
      linkage disequilibrium and cline shape to make inferences about migration and
      selection in the hybrid zone. RESULTS: The center of the hybrid zone has a high
      proportion of hybrids, about half of which were classified as F1s. Clines are
      narrow with respect to dispersal, and there are significant deviations from Hardy
      Weinberg equilibrium as well as nonrandom associations (linkage disequilibria)
      between alleles characteristic of each parental type. There is cytonuclear
      discordance, both in terms of introgression and the geographic position of
      mitochondrial versus nuclear clines. Genetic disequilibrium is concentrated on
      the eschscholtzii side of the zone. Nearly all hybrids possess klauberi mtDNA,
      indicating that most hybrids are formed from female klauberi mating with male
      eschscholtzii or male hybrids (but not vice versa). CONCLUSIONS: Our results are
      consistent with a tension zone trapped at an ecotone, with gene combinations
      characteristic of klauberi showing up on the eschscholtzii side of the zone due
      to asymmetric hybridization. We suggest that the observed asymmetry is best
      explained by increased discriminatory power of eschscholtzii females, or
      asymmetric postzygotic isolation. The relatively high frequency of hybrids,
      particularly F1s, contrasts with other contacts between the terminal forms, and
      with other contacts between other divergent Ensatina lineages, highlighting the
      diverse outcomes of secondary contact within a single species complex.

PMID- 21859448
TI  - The comparative burden of mild, moderate and severe fibromyalgia: results from a
      cross-sectional survey in the United States.
AB  - BACKGROUND: Fibromyalgia (FM) is characterized by chronic, widespread pain,
      fatigue, and other symptoms; yet few studies have comprehensively assessed its
      humanistic burden. This observational study evaluates the impact of FM severity
      on patients' symptoms, health-related quality of life (HRQoL), and productivity
      in the United States. METHODS: 203 FM subjects were recruited from 20 physician
      offices. Subjects completed a questionnaire including the EuroQol 5D (EQ-5D),
      Fibromyalgia Impact Questionnaire (FIQ), Multidimensional Assessment of Fatigue
      (MAF), Medical Outcomes Study Sleep Scale (MOS-SS), and Hospital Anxiety and
      Depression Scale (HADS) and questions about demographics, pain and other
      symptoms, HRQoL and productivity. FIQ total scores were used to define FM
      severity, with 0- < 39, 39- < 59, and 59-100, representing mild, moderate, and
      severe FM, respectively. Sites recorded subjects' clinical characteristics and FM
      treatment on case report forms using medical records. Summary statistics were
      calculated for continuous variables and frequency distributions for categorical
      variables. Differences across FM severity groups were evaluated using the Kruskal
      Wallis or Chi-square tests. Statistical significance was evaluated at the 0.05
      level. RESULTS: Mean (SD) age was 47.9 (10.9); 95% were female. Most (92%) were
      prescribed medication for FM; 24% and 66% reported moderate and severe FM,
      respectively. Mean (SD) scores were: 6.3 (2.1) for pain intensity; 0.35 (0.35)
      for EQ-5D; 30.7 (14.2) for MAF; 57.5 (18.4) for MOS-SS Sleep Problems Index; 10.2
      (4.8) for HADS anxiety and 9.4 (4.4) for HADS depression. Subjects with worse FM
      severity reported significantly increased pain severity, HRQoL, fatigue, sleep
      disturbance, anxiety and depression (p < 0.001). Overall, 50% of subjects
      reported some disruption in their employment due to FM; this differed across
      severity levels (p < 0.001). Employed subjects missed a mean (SD) of 1.8 (3.9)
      workdays during the past 4 weeks; this also differed across severity levels (p =
      0.03). CONCLUSIONS: FM imposes a substantial humanistic burden on patients in the
      United States, and leads to substantial productivity loss, despite treatment.
      This burden is higher among subjects with worse FM severity.

PMID- 21859449
TI  - Knowledge engineering tools for reasoning with scientific observations and
      interpretations: a neural connectivity use case.
AB  - BACKGROUND: We address the goal of curating observations from published
      experiments in a generalizable form; reasoning over these observations to
      generate interpretations and then querying this interpreted knowledge to supply
      the supporting evidence. We present web-application software as part of the
      'BioScholar' project (R01-GM083871) that fully instantiates this process for a
      well-defined domain: using tract-tracing experiments to study the neural
      connectivity of the rat brain. RESULTS: The main contribution of this work is to
      provide the first instantiation of a knowledge representation for experimental
      observations called 'Knowledge Engineering from Experimental Design' (KEfED)
      based on experimental variables and their interdependencies. The software has
      three parts: (a) the KEfED model editor - a design editor for creating KEfED
      models by drawing a flow diagram of an experimental protocol; (b) the KEfED data
      interface - a spreadsheet-like tool that permits users to enter experimental data
      pertaining to a specific model; (c) a 'neural connection matrix' interface that
      presents neural connectivity as a table of ordinal connection strengths
      representing the interpretations of tract-tracing data. This tool also allows the
      user to view experimental evidence pertaining to a specific connection.
      BioScholar is built in Flex 3.5. It uses Persevere (a noSQL database) as a
      flexible data store and PowerLoom(r) (a mature First Order Logic reasoning
      system) to execute queries using spatial reasoning over the BAMS neuroanatomical
      ontology. CONCLUSIONS: We first introduce the KEfED approach as a general
      approach and describe its possible role as a way of introducing structured
      reasoning into models of argumentation within new models of scientific
      publication. We then describe the design and implementation of our example
      application: the BioScholar software. This is presented as a possible biocuration
      interface and supplementary reasoning toolkit for a larger, more specialized
      bioinformatics system: the Brain Architecture Management System (BAMS).

PMID- 21859451
TI  - Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer
      cell line proliferation in vitro.
AB  - BACKGROUND: The synergic action of KHCO3 and D-ribose is tested on A72 and HTB
      126 cell lines proliferation using K:D-Rib solution. Altered Na+/K+ ATPase
      expression and activity were shown in patients with cancer. Studies in human
      epithelial-derived malignancies indicate that K+ depletion also occurs,
      contributing to the increased intracellular Na+/K+ ratio 1. D-ribose transformed
      to piruvate, enters into the Krebs's cycle and has a key role on energetic
      metabolism. The up-regulation of glycolysis in tumor cells is already well known
      and it is the rationale of F18-FDG PET diagnostic technique. D-ribose is
      synthesized by the non-oxidative transketolase PPP reaction. RESULTS: Results
      with different K:D-Rib concentrations show that MTT salt interferes with K:D-Rib
      solution and therefore this method is not reliable. The UV/VIS measurements show
      that K:D-Rib solutions reduce MTT salt to formazan in absence of cells. Cell
      proliferation has then been evaluated analysing the digital photos of the Giemsa
      stained cells with MCIDTM software. At 5 mM K:D-Rib concentration, the cell
      growth arrests between 48 h and 72 h; in fact the cell number after 48 h is
      around the same with respect to the control after 72 h. In case of HTB-126 human
      cancer cells, the growth rate was valuated counting the splitting times during 48
      days: control cells were split sixteen times while 5 mM treated cells eleven
      times. Most relevant, the clonogenic assay shows that nine colonies are formed in
      the control cells while only one is formed in the 5 mM and none in 10 mM treated
      cells. CONCLUSIONS: The K:D-Rib solution has an antioxidant behaviour also at low
      concentrations. Incubation with 5 mM K:D-Rib solution on A72 cells shows a
      cytostatic effect at 5 mM, but it needs more than 24 h of incubation time to
      evidence this effect on cell proliferation. At the same concentration on human
      HTB-126 cells, K:D-Rib solution shows a clear replication slowing but the
      cytostatic effect at 10 mM K:D-Rib solution only. Results on A72 cells indicate
      the K+ uptake could be determinant either to arrest or to slow down cell growth.

PMID- 21859450
TI  - Combination immunotherapy and active-specific tumor cell vaccination augments
      anti-cancer immunity in a mouse model of gastric cancer.
AB  - BACKGROUND: Active-specific immunotherapy used as an adjuvant therapeutic
      strategy is rather unexplored for cancers with poorly characterized tumor
      antigens like gastric cancer. The aim of this study was to augment a therapeutic
      immune response to a low immunogenic tumor cell line derived from a spontaneous
      gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg) transgenic
      mouse. METHODS: Mice were treated with a lymphodepleting dose of cyclophosphamide
      prior to reconstitution with syngeneic spleen cells and vaccination with a whole
      tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as
      LRAST). Anti-tumor activity to subcutaneous tumor challenge was examined in a
      prophylactic as well as a therapeutic setting and compared to corresponding
      controls. RESULTS: LRAST enhances tumor-specific T cell responses and efficiently
      inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended
      to slow down growth of established tumors. The improved anti-tumor immune
      response was accompanied by a transient decrease in the frequency and absolute
      number of CD4+CD25+FoxP3+ T cells (Tregs). CONCLUSIONS: Our data support the
      concept that whole tumor cell vaccination in a lymphodepleted and reconstituted
      host in combination with GM-CSF induces therapeutic tumor-specific T cells.
      However, the long-term efficacy of the treatment may be dampened by the
      recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are
      required to further evaluate this therapeutic vaccination protocol.

PMID- 21859452
TI  - Orbital metastases as first sign of metastatic spread in breast cancer: case
      report and review of the literature.
AB  - BACKGROUND: Intraorbital metastases of breast cancer is rare with only 3-10% of
      all ocular metastases. We report a case of orbital metastases as first sign of
      systemic metastatic spread in a female patient with breast cancer. METHODS: The
      patient had been diagnosed with breast cancer 3 years before. Her present
      complain was local pain, diplopia and periorbital swelling. A CT scan revealed
      extensive bony destruction of the orbital roof/anterior skull base. Bone
      scintigraphy demonstrated additional uptake at the level of the skull base,
      cervical spine, ilium and ribs suggesting metastatic spread to the skeleton. A
      navigation-assisted intraorbital biopsy from the orbital roof revealed a
      metastasis of breast cancer. With the confirmed diagnosis of metastatic breast
      cancer the patient was refered to the oncologist for further tumor staging. As
      further treatment she received systemic palliative chemotherapy in addition to
      intravenous treatment with bisphosphonates. CONCLUSION: In patients with a
      previous history of breast cancer who complain even of mild ophthalmologic
      symptoms such as local pain, periorbital edema, it is important to consider
      ocular or orbital metastatic disease. Adequate 3D-Imaging followed by a biopsy
      will usually confirm the diagnosis.

PMID- 21859453
TI  - Dietary total antioxidant capacity is inversely related to central adiposity as
      well as to metabolic and oxidative stress markers in healthy young adults.
AB  - BACKGROUND: Dietary total antioxidant capacity (TAC) has been assumed as a useful
      tool to assess the relationship between the cumulative antioxidant food capacity
      and several chronic disorders. The aim of this cross-sectional study was to
      investigate the potential relationships of dietary TAC with adiposity, metabolic
      and oxidative stress markers in healthy young adults. METHODS: This study
      enrolled 266 healthy subjects (105 men/ 161 women; 22 +/- 3 years-old; 22.0 +/-
      2.7 kg/m2). Dietary intake, anthropometry, blood pressure, lifestyle features,
      and biochemical data were assessed with validated procedures. RESULTS: In linear
      regression analyses, dietary TAC values were inversely associated with glycemia,
      total cholesterol:HDL-c ratio, triglycerides and oxidized-LDL concentrations, and
      positively associated with HDL-c concentrations, independently of gender, age,
      smoking status, physical activity, vitamin use supplement, waist circumference,
      energy intake, fatty acid intake. In addition, plasma TAC was negatively
      correlated with ox-LDL concentrations (r= -0.20, P = 0.003), independently of the
      assessed confounding variables. Finally, dietary TAC values were inversely
      related to waist circumference values (r= -0.17, P = 0.005) as well as to lower
      mild central obesity occurrence (waist circumference >= 80/ 94 cm for women/ men,
      respectively). CONCLUSION: Dietary TAC values are inversely associated with
      glucose and lipid biomarkers as well as with central adiposity measurements in
      healthy young adults, indicating dietary TAC as a useful tool to assess the
      health benefits of cumulative antioxidant capacity from food intake. In addition,
      the independent and inverse relationships of ox-LDL concentrations with dietary
      and plasma TAC respectively suggest a putative role of antioxidant rich-diet in
      the link between redox state and atherogenesis at early stage.

PMID- 21859455
TI  - Patterns of treatment seeking behavior for mental illnesses in Southwest
      Ethiopia: a hospital based study.
AB  - BACKGROUND: Early recognition of the signs and symptoms of mental health
      disorders is important because early intervention is critical to restoring the
      mental as well as the physical and the social health of an individual. This study
      sought to investigate patterns of treatment seeking behavior and associated
      factors for mental illness. METHODS: A quantitative, institution-based cross
      sectional study was conducted among 384 psychiatric patients at Jimma University
      Specialized Hospital (JUSH) located in Jimma, Ethiopia from March to April 2010.
      Data was collected using a pretested WHO encounter format by trained psychiatric
      nurses. Data was analyzed using SPSS V.16. RESULT: Major depression disorder 186
      (48.4%), schizophrenia 55 (14.3%) and other psychotic disorders 47 (12.2%) were
      the most common diagnoses given to the respondents. The median duration of
      symptoms of mental illness before contact to modern mental health service was
      52.1 weeks. The main sources of information for the help sought by the patients
      were found to be family 126 (32.8%) and other patients 75 (19.5%). Over a third
      of the patients 135 (35.2%), came directly to JUSH. Half of the patients sought
      traditional treatment from either a religious healer 116 (30.2%) or an herbalist
      77 (20.1%) before they came to the hospital. The most common explanations given
      for the cause of the mental illness were spiritual possession 198 (51.6%) and
      evil eye 61 (15.9%), whereas 73 (19.0%) of the respondents said they did not know
      the cause of mental illnesses. Nearly all of the respondents 379 (98.7%) believed
      that mental illness can be cured with modern treatment. Individuals who presented
      with abdominal pain and headache were more likely to seek care earlier. Being in
      the age group 31-40 years had significant statistical association with delayed
      treatment seeking behavior. CONCLUSIONS: There is significant delay in modern
      psychiatric treatment seeking in the majority of the cases. Traditional healers
      were the first place where help was sought for mental illness in this population.
      Most of the respondents claimed that mental illnesses were caused by supernatural
      factors. In contrast to their thoughts about the causes of mental illnesses
      however, most of the respondents believed that mental illnesses could be cured
      with biomedical treatment. Interventions targeted at improving public awareness
      about the causes and treatment of mental illness could reduce the delay in
      treatment seeking and improve treatment outcomes.

PMID- 21859454
TI  - Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse
      model of mammary cancer.
AB  - BACKGROUND: Several studies have demonstrated that sites of chronic inflammation
      are often associated with the establishment and growth of various malignancies. A
      common inflammatory condition in humans is autoimmune arthritis (AA). Although AA
      and cancer are different diseases, many of the underlying processes that
      contribute to the disorders of the joints and connective tissue that characterize
      AA also affect cancer progression and metastasis. Systemically, AA can lead to
      cellular infiltration and inflammation of the lungs. Several studies have
      reported statistically significant risk ratios between AA and breast cancer.
      Despite this knowledge being available, there has been minimal research linking
      breast cancer, arthritis, and metastasis associated with breast cancer. Notably
      both diseases are extremely prevalent in older post-menopausal women. METHODS: To
      establish the novel link between arthritis induced inflammation and secondary
      metastasis associated with breast cancer, PyV MT mice that spontaneously develop
      mammary gland carcinoma were injected with Type II collagen (CII) to induce
      arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition.
      The sites of secondary metastasis and the associated inflammatory
      microenvironment were evaluated. RESULTS: A significant increase in breast cancer
      associated secondary metastasis to the lungs and bones was observed in the
      arthritic versus the non-arthritic PyV MT mice along with an increase in primary
      tumor burden. We report significant increases in the levels of interstitial
      cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL
      17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin
      like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in
      the arthritic lung and bone milieu as well as in the circulation. These pro
      inflammatory cytokines along with the inflammatory microenvironment may be the
      underlying factors facilitating tumor progression and metastasis in arthritic PyV
      MT mice. This was further substantiated by treatment with celecoxib, an anti
      inflammatory drug + alphaIL-17 antibody that significantly reduced the secondary
      metastasis to lung and bone. CONCLUSIONS: The data generated not only reveal the
      underlying mechanism of high susceptibility to bone and lung metastasis in an
      arthritic condition but our combination therapies may lead to treatment
      modalities that will be capable of reducing tumor burden, and preventing relapse
      and metastasis in arthritic patients with breast cancer.

PMID- 21859456
TI  - Enhanced UV photosensitivity from rapid thermal annealed vertically aligned ZnO
      nanowires.
AB  - We report on the major improvement in UV photosensitivity and faster
      photoresponse from vertically aligned ZnO nanowires (NWs) by means of rapid
      thermal annealing (RTA). The ZnO NWs were grown by vapor-liquid-solid method and
      subsequently RTA treated at 700 degrees C and 800 degrees C for 120 s. The UV
      photosensitivity (photo-to-dark current ratio) is 4.5 * 103 for the as-grown NWs
      and after RTA treatment it is enhanced by a factor of five. The photocurrent (PC)
      spectra of the as-grown and RTA-treated NWs show a strong peak in the UV region
      and two other relatively weak peaks in the visible region. The photoresponse
      measurement shows a bi-exponential growth and bi-exponential decay of the PC from
      as-grown as well as RTA-treated ZnO NWs. The growth and decay time constants are
      reduced after the RTA treatment indicating a faster photoresponse. The dark
      current-voltage characteristics clearly show the presence of surface defects
      related trap centers on the as-grown ZnO NWs and after RTA treatment it is
      significantly reduced. The RTA processing diminishes the surface defect-related
      trap centers and modifies the surface of the ZnO NWs, resulting in enhanced PC
      and faster photoresponse. These results demonstrated the effectiveness of RTA
      processing for achieving improved photosensitivity of ZnO NWs.

PMID- 21859457
TI  - Genetic structure and seed-mediated dispersal rates of an endangered shrub in a
      fragmented landscape: a case study for Juniperus communis in northwestern Europe.
AB  - BACKGROUND: Population extinction risk in a fragmented landscape is related to
      the differential ability of the species to spread its genes across the landscape.
      The impact of landscape fragmentation on plant population dynamics will therefore
      vary across different spatial scales. We quantified successful seed-mediated
      dispersal of the dioecious shrub Juniperus communis in a fragmented landscape
      across northwestern Europe by using amplified fragment length polymorphism (AFLP)
      markers. Furthermore we investigated the genetic diversity and structure on two
      spatial scales: across northwestern Europe and across Flanders (northern
      Belgium). We also studied whether seed viability and populations size were
      correlated with genetic diversity. RESULTS: Unexpectedly, estimated seed-mediated
      dispersal rates were quite high and ranged between 3% and 14%. No population
      differentiation and no spatial genetic structure were detected on the local,
      Flemish scale. A significant low to moderate genetic differentiation between
      populations was detected at the regional, northwest European scale (PhiPT =
      0.10). In general, geographically nearby populations were also genetically
      related. High levels of within-population genetic diversity were detected but no
      correlation was found between any genetic diversity parameter and population size
      or seed viability. CONCLUSIONS: In northwestern Europe, landscape fragmentation
      has lead to a weak isolation-by-distance pattern but not to genetic
      impoverishment of common juniper. Substantial rates of successful migration by
      seed-mediated gene flow indicate a high dispersal ability which could enable
      Juniperus communis to naturally colonize suitable habitats. However, it is not
      clear whether the observed levels of migration will suffice to counterbalance the
      effects of genetic drift in small populations on the long run.

PMID- 21859458
TI  - Potential risk factors associated with human encephalitis: application of
      canonical correlation analysis.
AB  - BACKGROUND: Infection of the CNS is considered to be the major cause of
      encephalitis and more than 100 different pathogens have been recognized as
      causative agents. Despite being identified worldwide as an important public
      health concern, studies on encephalitis are very few and often focus on
      particular types (with respect to causative agents) of encephalitis (e.g. West
      Nile, Japanese, etc.). Moreover, a number of other infectious and non-infectious
      conditions present with similar symptoms, and distinguishing encephalitis from
      other disguising conditions continues to a challenging task. METHODS: We used
      canonical correlation analysis (CCA) to assess associations between set of
      exposure variable and set of symptom and diagnostic variables in human
      encephalitis. Data consists of 208 confirmed cases of encephalitis from a
      prospective multicenter study conducted in the United Kingdom. We used a
      covariance matrix based on Gini's measure of similarity and used permutation
      based approaches to test significance of canonical variates. RESULTS: Results
      show that weak pair-wise correlation exists between the risk factor (exposure and
      demographic) and symptom/laboratory variables. However, the first canonical
      variate from CCA revealed strong multivariate correlation (rho = 0.71, se = 0.03,
      p = 0.013) between the two sets. We found a moderate correlation (rho = 0.54, se
      = 0.02) between the variables in the second canonical variate, however, the value
      is not statistically significant (p = 0.68). Our results also show that a very
      small amount of the variation in the symptom sets is explained by the exposure
      variables. This indicates that host factors, rather than environmental factors
      might be important towards understanding the etiology of encephalitis and
      facilitate early diagnosis and treatment of encephalitis patients. CONCLUSIONS:
      There is no standard laboratory diagnostic strategy for investigation of
      encephalitis and even experienced physicians are often uncertain about the cause,
      appropriate therapy and prognosis of encephalitis. Exploration of human
      encephalitis data using advanced multivariate statistical modelling approaches
      that can capture the inherent complexity in the data is, therefore, crucial in
      understanding the causes of human encephalitis. Moreover, application of
      multivariate exploratory techniques will generate clinically important hypotheses
      and offer useful insight into the number and nature of variables worthy of
      further consideration in a confirmatory statistical analysis.

PMID- 21859459
TI  - Response by sex to statin plus ezetimibe or statin monotherapy: a pooled analysis
      of 22,231 hyperlipidemic patients.
AB  - BACKGROUND: Despite documented benefits of lipid-lowering treatment in women, a
      considerable number are undertreated, and fewer achieve treatment targets vs.
      men. METHODS: Data were combined from 27 double-blind, active or placebo
      controlled studies that randomized adult hypercholesterolemic patients to statin
      or statin+ezetimibe. Consistency of treatment effect among men (n = 11,295) and
      women (n = 10,499) was assessed and percent of men and women was calculated to
      evaluate the between-treatment ability to achieve specified treatment levels
      between sexes. RESULTS: Baseline lipids and hs-CRP were generally higher in women
      vs. men. Between-treatment differences were significant for both sexes (all p <
      0.001 except apolipoprotein A-I in men = 0.0389). Men treated with
      ezetimibe+statin experienced significantly greater changes in LDL-C (p = 0.0066),
      non-HDL-C, total cholesterol, triglycerides, HDL-C, apolipoprotein A-I (all p <
      0.0001) and apolipoprotein B (p = 0.0055) compared with women treated with
      ezetimibe+statin. The odds of achieving LDL-C < 100 mg/dL, apolipoprotein B < 90
      mg/dL and the dual target [LDL-C < 100 mg/dL & apoliprotein B < 90 mg/dL] was
      significantly greater for women vs. men and the odds of achieving hs-CRP < 1 and
      < 2 mg/L and dual specified levels of [LDL-C < 100 mg/dL and hs-CRP < 2 mg/L]
      were significantly greater for men vs. women. Women reported significantly more
      gall-bladder-related, gastrointestinal-related, and allergic reaction or rash
      related adverse events (AEs) vs. men (no differences between treatments). Men
      reported significantly more CK elevations (no differences between treatments) and
      hepatitis-related AEs vs. women (significantly more with ezetimibe+simvastatin
      vs. statin). CONCLUSIONS: These results suggest that small sex-related
      differences may exist in response to lipid-lowering treatment and achievement of
      specified lipid and hs-CRP levels, which may have implications when managing
      hypercholesterolemia in women.

PMID- 21859461
TI  - Glucagonoma syndrome: a case report.
AB  - INTRODUCTION: Glucagonoma syndrome is a rare paraneoplastic phenomenon, with an
      estimated incidence of one in 20 million, characterized by necrolytic migratory
      erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis,
      cheilitis, steatorrhea, diarrhea, venous thrombosis and neuropsychiatric
      disturbances in the setting of a glucagon-producing alpha-cell tumor of the
      pancreas. Necrolytic migratory erythema is the presenting manifestation in the
      majority of cases, so its early suspicion and correct diagnosis is a key factor
      in the management of the patient. CASE PRESENTATION: We present the case of a 70
      year-old Caucasian woman with glucagonoma syndrome due to an alpha-cell tumor
      located in the tail of the pancreas, successfully treated with surgical
      resection. CONCLUSION: Clinicians should be aware of the unusual initial
      manifestations of glucagonoma. Early diagnosis allows complete surgical resection
      of the neoplasm and provides the only chance of a cure.

PMID- 21859460
TI  - Distinct configurations of protein complexes and biochemical pathways revealed by
      epistatic interaction network motifs.
AB  - BACKGROUND: Gene and protein interactions are commonly represented as networks,
      with the genes or proteins comprising the nodes and the relationship between them
      as edges. Motifs, or small local configurations of edges and nodes that arise
      repeatedly, can be used to simplify the interpretation of networks. RESULTS: We
      examined triplet motifs in a network of quantitative epistatic genetic
      relationships, and found a non-random distribution of particular motif classes.
      Individual motif classes were found to be associated with different functional
      properties, suggestive of an underlying biological significance. These
      associations were apparent not only for motif classes, but for individual
      positions within the motifs. As expected, NNN (all negative) motifs were strongly
      associated with previously reported genetic (i.e. synthetic lethal) interactions,
      while PPP (all positive) motifs were associated with protein complexes. The two
      other motif classes (NNP: a positive interaction spanned by two negative
      interactions, and NPP: a negative spanned by two positives) showed very distinct
      functional associations, with physical interactions dominating for the former but
      alternative enrichments, typical of biochemical pathways, dominating for the
      latter. CONCLUSION: We present a model showing how NNP motifs can be used to
      recognize supportive relationships between protein complexes, while NPP motifs
      often identify opposing or regulatory behaviour between a gene and an associated
      pathway. The ability to use motifs to point toward underlying biological
      organizational themes is likely to be increasingly important as more extensive
      epistasis mapping projects in higher organisms begin.

PMID- 21859462
TI  - Identification of one critical amino acid that determines a conformational
      neutralizing epitope in the capsid protein of porcine circovirus type 2.
AB  - BACKGROUND: Porcine circovirus type 2 (PCV2) is associated with post-weaning
      multisystemic wasting syndrome (PMWS) in pigs. Currently, there is considerable
      interest in the immunology of PCV2; in particular, the immunological properties
      of the capsid protein. This protein is involved in PCV2 immunogenicity and is a
      potential target for vaccine development. In this study, we identified one
      critical amino acid that determines a conformational neutralizing epitope in the
      capsid protein of PCV2. RESULTS: One monoclonal antibody (mAb; 8E4), against the
      capsid protein of PCV2, was generated and characterized in this study. 8E4
      reacted with the genotype PCV2a (CL, LG and JF2) strains but not PCV2b (YJ, SH
      and JF) strains by an immunoperoxidase monolayer assay (IPMA) and a capture
      ELISA. Furthermore, the mAb had the capacity to neutralize PCV2a (CL, LG and JF2)
      strains but not PCV2b (YJ, SH and JF) strains. One critical amino acid that
      determined a conformational neutralizing epitope was identified using mAb 8E4 and
      PCV2 infectious clone technique. Amino acid residues 47-72 in the capsid protein
      of PCV2a/CL were replaced with the corresponding region of PCV2b/YJ, and the
      reactivity of mAb 8E4 was lost. Further experiments demonstrated that one amino
      acid substitution, the alanine for arginine at position 59 (A59R) in the capsid
      protein of PCV2a (CL, LG and JF2) strains, inhibited completely the
      immunoreactivity of three PCV2a strains with mAb 8E4. CONCLUSIONS: It is
      concluded that the alanine at position 59 in the capsid protein of PCV2a (CL, LG
      and JF2) strains is a critical amino acid, which determines one neutralizing
      epitope of PCV2a (CL, LG and JF2) strains. This study provides valuable
      information for further in-depth mapping of the conformational neutralizing
      epitope, understanding antigenic difference among PCV2 strains, and development
      of a useful vaccine for control of PCV2-associated disease.

PMID- 21859463
TI  - Giardia lamblia: a major parasitic cause of childhood diarrhoea in patients
      attending a district hospital in Ghana.
AB  - BACKGROUND: Acute childhood diarrhoea remains one of the leading causes of
      childhood morbidity and mortality in developing countries. The WHO has
      accordingly underlined the need for epidemiological surveys of infantile
      diarrhoea in all geographical areas. This study was conducted to determine the
      incidence of intestinal parasites among stool samples from children examined at a
      secondary health care facility in a rural area of Ghana. METHOD: A retrospective
      study was conducted to investigate the incidence of intestinal parasites among
      children who had their stools examined at the Agogo Hospital laboratory. Stool
      microscopy results from January 2006 through May 2009 were obtained from archived
      records of the laboratory. Results for children less than 18 years were
      transcribed unto a standardized datasheet, entered into an electronic database
      designed using Microsoft(r) access 2007 and analyzed using Stata/SE11.1
      statistical software. The incidences of the parasites were determined and
      presented with their Poisson exact 95% confidence intervals for the various ages.
      RESULTS: The median age of the 1080 children included in the study was 5 years
      (IQR: 2-12 years) with 51.9% being females. The overall incidence of all
      parasites was 114 per 1000 with Giardia lamblia being the most common (89.5%).
      Children aged less than a year had the lowest parasite incidence of 13 per 1000
      with all being Giardia lamblia, while those aged 15-17 years had the highest of
      169 per 1000. The incidence for Giardia lamblia only was lowest at 13 per 1000
      for those under a year old, highest at 152 per 1000 for the 15-17 year group and
      97 per 1000 for all ages combined. There was a significant rise in incidence of
      Giardia lamblia with age (Trend x2 = 18.6, p < 0.001). Five (4.3%) of the 118
      positive stool samples had mixed parasites infection. Enterobius vermicularis,
      Taenia spp and Trichuris trichiura were not seen in any of the stool samples.
      CONCLUSION: Giardia lamblia is the most prevalent intestinal parasite in examined
      stool samples of children within the Ashanti Akim North Municipality and its
      prevalence significantly increases with age. Measures must be put in place to
      educate the community on proper personal hygiene to reduce giardiasis.

PMID- 21859465
TI  - The influence of the cage system and colonisation of Salmonella Enteritidis on
      the microbial gut flora of laying hens studied by T-RFLP and 454 pyrosequencing.
AB  - BACKGROUND: In the EU conventional cages for laying hens are forbidden beginning
      in January 2012, however concerns about a higher transmission rate of Salmonella
      in alternative cages systems have been raised. The extent to which cage systems
      may affect the intestinal microbiota of laying hens is not known, and different
      microbiota may demonstrate different resistance towards colonization with
      Salmonella. To investigate this, ileal and caecal samples from two experimental
      studies where laying hens were inoculated with Salmonella Enteritidis and housed
      in different systems (conventional cage, furnished cage or aviary), were compared
      using Terminal Restriction Fragment Length Polymorphism (T-RFLP). The
      distribution of genera in the microbiota in caecum was furthermore described by
      next generation sequencing of 16S rDNA libraries. RESULTS: Hens in the same cage
      type developed similar T-RFLP fingerprints of the ileal and caecal microbiota,
      and these could be separated from layers in the other cages types. No significant
      difference in the fingerprint profiles could be observed between Salmonella
      positive and negative samples from same cage. By deep sequencing of 16S rDNA
      libraries from caecum, 197 different Operational Taxonomic Units (OTU) were
      identified, and 195 and 196 OTU respectively, were found in hens in aviary and
      furnished cages, but only 178 OTU of these were recovered from conventional
      cages. The ratio between the dominating phyla or families and genera in the
      microbiota remained fairly constant throughout the study. Faecalibacterium and
      Butyricimonas were the most prevalent genera found in the caecal microbiota of
      layers irrespective of the cage type. CONCLUSIONS: Hens confined in the same cage
      group tend to develop similar microbiota in their ileum and caecum possibly due
      to isolation, while differences in the microbiota between cages may be caused by
      environmental or individual bird factors. Although the cages type had influence
      on composition of the microbiota in the layers by promoting higher diversity in
      furnished and aviary systems, we did not observe differences in colonization and
      excretion pattern of Salmonella from these groups. We suggest, that differences
      in group size and exposure to a more faecally contaminated environment in the
      alternative systems may explain the observed differences in diversity of the
      caecal microbiota.

PMID- 21859464
TI  - Messing up disorder: how do missense mutations in the tumor suppressor protein
      APC lead to cancer?
AB  - Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene strongly
      predispose to development of gastro-intestinal tumors. Central to the tumorigenic
      events in APC mutant cells is the uncontrolled stabilization and transcriptional
      activation of the protein beta-catenin. Many questions remain as to how APC
      controls beta-catenin degradation. Remarkably, the large C-terminal region of
      APC, which spans over 2000 amino acids and includes critical regions in
      downregulating beta-catenin, is predicted to be natively unfolded. Here we
      discuss how this uncommonly large disordered region may help to coordinate the
      multiple cellular functions of APC. Recently, a significant number of germline
      and somatic missense mutations in the central region of APC were linked to
      tumorigenesis in the colon as well as extra-intestinal tissues. We classify and
      localize all currently known missense mutations in the APC structure. The
      molecular basis by which these mutations interfere with the function of APC
      remains unresolved. We propose several mechanisms by which cancer-related
      missense mutations in the large disordered domain of APC may interfere with tumor
      suppressor activity. Insight in the underlying molecular events will be
      invaluable in the development of novel strategies to counter dysregulated Wnt
      signaling by APC mutations in cancer.

PMID- 21859466
TI  - Magnetic resonance imaging detects significant sex differences in human
      myocardial strain.
AB  - BACKGROUND: The pathophysiology responsible for the significant outcome
      disparities between men and women with cardiac disease is largely unknown.
      Further investigation into basic cardiac physiological differences between the
      sexes is needed. This study utilized magnetic resonance imaging (MRI)-based
      multiparametric strain analysis to search for sex-based differences in regional
      myocardial contractile function. METHODS: End-systolic strain (circumferential,
      longitudinal, and radial) was interpolated from MRI-based radiofrequency tissue
      tagging grid point displacements in each of 60 normal adult volunteers (32
      females). RESULTS: The average global left ventricular (LV) strain among normal
      female volunteers (n = 32) was significantly larger in absolute value
      (functionally better) than in normal male volunteers (n = 28) in both the
      circumferential direction (Male/Female = -0.19 +/- 0.02 vs. -0.21 +/- 0.02; p =
      0.025) and longitudinal direction (Male/Female = -0.14 +/- 0.03 vs. -0.16 +/-
      0.02; p = 0.007). CONCLUSIONS: The finding of significantly larger
      circumferential and longitudinal LV strain among normal female volunteers
      suggests that baseline contractile differences between the sexes may contribute
      to the well-recognized divergence in cardiovascular disease outcomes. Further
      work is needed in order to determine the pathologic changes that occur in LV
      strain between women and men with the onset of cardiovascular disease.

PMID- 21859467
TI  - Metabolomic phenotyping of a cloned pig model.
AB  - BACKGROUND: Pigs are widely used as models for human physiological changes in
      intervention studies, because of the close resemblance between human and porcine
      physiology and the high degree of experimental control when using an animal
      model. Cloned animals have, in principle, identical genotypes and possibly also
      phenotypes and this offer an extra level of experimental control which could
      possibly make them a desirable tool for intervention studies. Therefore, in the
      present study, we address how phenotype and phenotypic variation is affected by
      cloning, through comparison of cloned pigs and normal outbred pigs. RESULTS: The
      metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by
      nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio
      fluids including plasma, bile and urine. The metabolic phenotype of the cloned
      pigs was compared with normal outbred pigs (n = 6) by multivariate data analysis,
      which revealed differences in the metabolic phenotypes. Plasma lactate was higher
      for cloned vs control pigs, while multiple metabolites were altered in the bile.
      However a lower inter-individual variability for cloned pigs compared with
      control pigs could not be established. CONCLUSIONS: From the present study we
      conclude that cloned and normal outbred pigs are phenotypically different.
      However, it cannot be concluded that the use of cloned animals will reduce the
      inter-individual variation in intervention studies, though this is based on a
      limited number of animals.

PMID- 21859468
TI  - Subcoronary versus supracoronary aortic stenosis. An experimental evaluation.
AB  - BACKGROUND: Valvular aortic stenosis is the most common cause of left ventricular
      hypertrophy due to gradually increasing pressure work. As the stenosis develop
      the left ventricular hypertrophy may lead to congestive heart failure, increased
      risk of perioperative complications and also increased risk of sudden death. A
      functional porcine model imitating the pathophysiological nature of valvular
      aortic stenosis is very much sought after in order to study the geometrical and
      pathophysiological changes of the left ventricle, timing of surgery and also
      pharmacological therapy in this patient group. Earlier we developed a porcine
      model for aortic stenosis based on supracoronary aortic banding, this model may
      not completely imitate the pathophysiological changes that occurs when valvular
      aortic stenosis is present including the coronary blood flow. It would therefore
      be desirable to optimize this model according to the localization of the
      stenosis. METHODS: In 20 kg pigs subcoronary (n = 8), supracoronary aortic
      banding (n = 8) or sham operation (n = 4) was preformed via a left lateral
      thoracotomy. The primary endpoint was left ventricular wall thickness; secondary
      endpoints were heart/body weight ratio and the systolic/diastolic blood flow
      ratio in the left anterior descending coronary. Statistical evaluation by oneway
      anova and unpaired t-test. RESULTS: Sub- and supracoronary banding induce an
      equal degree of left ventricular hypertrophy compared with the control group. The
      coronary blood flow ratio was slightly but not significantly higher in the
      supracoronary group (ratio = 0.45) compared with the two other groups
      (subcoronary ratio = 0.36, control ratio = 0.34). CONCLUSIONS: A human
      pathophysiologically compatible porcine model for valvular aortic stenosis was
      developed by performing subcoronary aortic banding. Sub- and supracoronary aortic
      banding induce an equal degree of left ventricular hypertrophy. This model may be
      valid for experimental investigations of aortic valve stenosis but studies of
      left ventricular hypertrophy can be studied equally well by graduated
      constriction of the ascending aorta.

PMID- 21859469
TI  - Hybrid management of a spontaneous ilio-iliac arteriovenous fistula: a case
      report.
AB  - INTRODUCTION: Spontaneous iliac arteriovenous fistulae are a rare clinical
      entity. Such localized fistulation is usually a result of penetrating traumatic
      or iatrogenic injury. Clinical presentation can vary greatly but commonly
      includes back pain, high-output congestive cardiac failure and the presence of an
      abdominal bruit. Diagnosis, therefore, is often incidental or delayed. CASE
      PRESENTATION: We report a case of a spontaneous ilio-iliac arteriovenous fistula
      in a 68-year-old Caucasian man detected following presentation with unilateral
      claudication and congestive cardiac failure. Following computed tomography
      evaluation, the fistula was successfully treated with a combined endovascular
      (aorto-uni-iliac device) and open (femoro-femoral crossover) approach.
      CONCLUSION: Endovascular surgery has revolutionized the management of such
      fistulae and we report an interesting case of a high-output iliac arteriovenous
      fistulae successfully treated with a hybrid vascular approach.

PMID- 21859470
TI  - An evaluation of the completeness of safety reporting in reports of complementary
      and alternative medicine trials.
AB  - BACKGROUND: Adequate reporting of safety in publications of randomized controlled
      trials (RCTs) is a pre-requisite for accurate and comprehensive profile
      evaluation of conventional as well as complementary and alternative medicine
      (CAM) treatments. Clear and concise information on the definition, frequency, and
      severity of adverse events (AEs) is necessary for assessing the benefit-harm
      ratio of any intervention. The objectives of this study are to assess the quality
      of safety reporting in CAM RCTs; to explore the influence of different trial
      characteristics on the quality of safety reporting. METHODS: Survey of safety
      reporting in RCTs published in 2009 across 15 widely used CAM interventions
      identified from the Cochrane Collaboration's CAM Field specialized register of
      trials. Primary outcome measures, the adequacy of reporting of AEs; was defined
      and categorized according to the CONSORT for harms extension; the percentage of
      words devoted to the reporting of safety in the entire report and in the results
      section. RESULTS: Two-hundred and five trials were included in the review. Of
      these, 15% (31/205) reported that no harms were observed during the trial period.
      Of the remaining 174 trials reporting any safety information, only 21% (36/174)
      had adequate safety reporting.For all trials, the median percentage of words
      devoted to the reporting of safety in the results section was 2.6. Moreover, 69%
      (n = 141) of all trials devoted a lesser or equal percentage of words to safety
      compared to author affiliations. Of the predictor variables used in regression
      analysis, multicenter trials had more words devoted to safety in the results
      section than single centre trials (P = 0.045). CONCLUSIONS: An evaluation of
      safety reporting in the reports of CAM RCTs across 15 different CAM interventions
      demonstrated that the reporting of harms was largely inadequate. The quality of
      reporting safety information in primary reports of CAM randomized trials requires
      improvement.

PMID- 21859471
TI  - Structural aspects of leg-to-gonopod metamorphosis in male helminthomorph
      millipedes (Diplopoda).
AB  - BACKGROUND: In the adult males of helminthomorph millipedes, one or two pairs of
      legs in the anterior part of the trunk are strongly modified into sexual
      appendages (gonopods) used for sperm transfer during the copula. Gonopods
      differentiate in an advanced phase of post-embryonic development, in most cases
      as replacement for the walking legs of the seventh trunk ring, as these first
      regress to tiny primordia, to eventually develop into gonopods at a subsequent
      stadium. These extremely localized but dramatic changes have been described as a
      non-systemic metamorphosis. In the present study we describe morphological and
      anatomical changes of trunk ring VII associated with non-systemic metamorphosis
      in four helminthomorph species. RESULTS: As documented here for the first time by
      means of traditional histology methods and new techniques based on confocal laser
      scanning microscopy, the external modifications caused by non-systemic
      metamorphosis are associated to a huge rearrangement of internal anatomy, mostly
      due to the development of gonopod apodemes and extrinsic muscles. CONCLUSIONS:
      Internal changes in the seventh trunk ring, locally leading to the dorsal
      displacement of the ventral nerve cord and the digestive tract, are modulated in
      a taxon-specific manner, and are very conspicuous in the blaniulids Nopoiulus
      kochii and Blaniulus guttulatus, with likely major functional consequences.

PMID- 21859472
TI  - Multivisceral resection of pancreatic neuroendocrine tumours: a report of two
      cases.
AB  - Pancreatic neuroendocrine tumours (pNETs) are rare and surgical resection offers
      the only possibility of cure for localised disease. The role of surgery in the
      setting of locally advanced and metastatic disease is more controversial.
      Emerging data suggests that synchronous surgical resection of pancreas and liver
      may be associated with increased survival. We report two cases of synchronous,
      one stage multivisceral resections for pNET and associated reconstruction. We
      highlight the technical issues involved in such extensive resections and
      demonstrate that one stage multivisceral operations can be achieved safely.

PMID- 21859473
TI  - Submicroscopic interstitial deletion of chromosome 11q22.3 in a girl with mild
      mental retardation and facial dysmorphism: Case report.
AB  - BACKGROUND: Except for terminal deletions that lead to Jacobsen syndrome,
      interstitial deletions involving the long arm of chromosome 11 are not frequently
      reported. A clinically distinct phenotype is usually observed in these cases, and
      no clear genotype-phenotype correlation is proposed. RESULTS: Here we present a
      case study of a 5-year-old girl with de novo submicroscopic deletion of
      chromosome 11q22.3 with mild mental retardation and facial dysmorphism. A
      standard cytogenetic analysis did not reveal any structural aberrations. In
      contrary, array-CGH analysis indicated a small deletion of 11q22.3. DISCUSSION:
      To our knowledge, this is the smallest 11q22.3 deletion reported in literature,
      containing nine RefSeq genes. Although none of the deleted genes are obvious
      candidates for the features observed in our patient, genes CUL5 and SLN could
      play a key role in the features described.

PMID- 21859474
TI  - Malignant catarrhal fever induced by Alcelaphine herpesvirus 1 is characterized
      by an expansion of activated CD3+CD8+CD4- T cells expressing a cytotoxic
      phenotype in both lymphoid and non-lymphoid tissues.
AB  - Alcelaphine herpesvirus 1 (AlHV-1) is carried by wildebeest asymptomatically. It
      causes a fatal lymphoproliferative disease named wildebeest-derived malignant
      catarrhal fever (WD-MCF) when cross-species transmitted to a variety of
      susceptible species of the Artiodactyla order. WD-MCF can be reproduced
      experimentally in rabbits. In a previous report, we demonstrated that WD-MCF
      induced by AlHV-1 is associated with a severe proliferation of CD8(+) T cells in
      the lymphoid tissues. Here, we further studied the mononuclear leukocytic
      populations in both the lymphoid (throughout the infection and at time of
      euthanasia) and non-lymphoid (at time of euthanasia) organs during WD-MCF induced
      experimentally in rabbits. To reach that goal, we performed multi-colour flow
      cytometry stainings. The results obtained demonstrate that the development of WD
      MCF correlates in peripheral blood with a severe increase of CD8(+) cell
      percentages; and that CD3(+)CD8(+)CD4(-) T cells were the predominant cell type
      in both lymphoid and non-lymphoid organs at time of euthanasia. Further
      characterization of the mononuclear leukocytes isolated from both lymphoid and
      non-lymphoid tissues revealed that the CD8(+) T cells express high levels of the
      activation markers CD25 and CD44, produce high amount of gamma-interferon (IFN
      gamma) and perforin, and showed a reduction of interleukin-2 (IL-2) gene
      expression. These data demonstrate that the development of WD-MCF is associated
      with the expansion and infiltration of activated and cytotoxic CD3(+)CD8(+)CD4(-)
      T cells secreting high amount of IFN-gamma but low IL-2.

PMID- 21859475
TI  - Differential patterns of intronic and exonic DNA regions with respect to RNA
      polymerase II occupancy, nucleosome density and H3K36me3 marking in fission
      yeast.
AB  - BACKGROUND: The generation of mature mRNAs involves interconnected processes,
      including transcription by RNA polymerase II (Pol II), modification of histones,
      and processing of pre-mRNAs through capping, intron splicing, and
      polyadenylation. These processes are thought to be integrated, both spatially and
      temporally, but it is unclear how these connections manifest at a global level
      with respect to chromatin patterns and transcription kinetics. We sought to
      clarify the relationships between chromatin, transcription and splicing using
      multiple genome-wide approaches in fission yeast. RESULTS: To investigate these
      functional interdependencies, we determined Pol II occupancy across all genes
      using high-density tiling arrays. We also performed ChIP-chip on the same array
      platform to globally map histone H3 and its H3K36me3 modification, complemented
      by formaldehyde-assisted isolation of regulatory elements (FAIRE). Surprisingly,
      Pol II occupancy was higher in introns than in exons, and this difference was
      inversely correlated with gene expression levels at a global level. Moreover,
      introns showed distinct distributions of histone H3, H3K36me3 and FAIRE signals,
      similar to those at promoters and terminators. These distinct transcription and
      chromatin patterns of intronic regions were most pronounced in poorly expressed
      genes. CONCLUSIONS: Our findings suggest that Pol II accumulates at the 3' ends
      of introns, leading to substantial transcriptional delays in weakly transcribed
      genes. We propose that the global relationship between transcription, chromatin
      remodeling, and splicing may reflect differences in local nuclear environments,
      with highly expressed genes being associated with abundant processing factors
      that promote effective intron splicing and transcriptional elongation.

PMID- 21859477
TI  - Hybridization in East African swarm-raiding army ants.
AB  - BACKGROUND: Hybridization can have complex effects on evolutionary dynamics in
      ants because of the combination of haplodiploid sex-determination and
      eusociality. While hybrid non-reproductive workers have been found in a range of
      species, examples of gene-flow via hybrid queens and males are rare. We studied
      hybridization in East African army ants (Dorylus subgenus Anomma) using
      morphology, mitochondrial DNA sequences, and nuclear microsatellites. RESULTS:
      While the mitochondrial phylogeny had a strong geographic signal, different
      species were not recovered as monophyletic. At our main study site at Kakamega
      Forest, a mitochondrial haplotype was shared between a "Dorylus molestus-like"
      and a "Dorylus wilverthi-like" form. This pattern is best explained by
      introgression following hybridization between D. molestus and D. wilverthi.
      Microsatellite data from workers showed that the two morphological forms
      correspond to two distinct genetic clusters, with a significant proportion of
      individuals being classified as hybrids. CONCLUSIONS: We conclude that
      hybridization and gene-flow between the two army ant species D. molestus and D.
      wilverthi has occurred, and that mating between the two forms continues to
      regularly produce hybrid workers. Hybridization is particularly surprising in
      army ants because workers have control over which males are allowed to mate with
      a young virgin queen inside the colony.

PMID- 21859476
TI  - Cistrome: an integrative platform for transcriptional regulation studies.
AB  - The increasing volume of ChIP-chip and ChIP-seq data being generated creates a
      challenge for standard, integrative and reproducible bioinformatics data analysis
      platforms. We developed a web-based application called Cistrome, based on the
      Galaxy open source framework. In addition to the standard Galaxy functions,
      Cistrome has 29 ChIP-chip- and ChIP-seq-specific tools in three major categories,
      from preliminary peak calling and correlation analyses to downstream genome
      feature association, gene expression analyses, and motif discovery. Cistrome is
      available at http://cistrome.org/ap/.

PMID- 21859478
TI  - Decreased expression of axon-guidance receptors in the anterior cingulate cortex
      in autism.
AB  - BACKGROUND: Axon-guidance proteins play a crucial role in brain development. As
      the dysfunction of axon-guidance signaling is thought to underlie the
      microstructural abnormalities of the brain in people with autism, we examined the
      postmortem brains of people with autism to identify any changes in the expression
      of axon-guidance proteins. RESULTS: The mRNA and protein expression of axon
      guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout
      2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary
      motor cortex of autistic brains (n = 8 and n = 7, respectively) and control
      brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR
      (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative
      expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the
      autistic group than in the control group. The protein levels of these three genes
      were further analyzed by western blotting, which showed that the immunoreactive
      values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the
      ACC of the autistic brains compared with control brains. CONCLUSIONS: In this
      study, we found decreased expression of axon-guidance proteins such as PLXNA4 and
      ROBO2 in the brains of people with autism, and suggest that dysfunctional axon
      guidance protein expression may play an important role in the pathophysiology of
      autism.

PMID- 21859479
TI  - JNK suppression is essential for 17beta-Estradiol inhibits prostaglandin E2
      Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer
      cells.
AB  - BACKGROUND: Epidemiological studies demonstrate that the incidence and mortality
      rates of colorectal cancer in women are lower than in men. However, it is unknown
      if 17beta-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)
      induced cellular motility in human colon cancer cells. METHODS: We analyzed the
      protein expression of urokinase plasminogen activator (uPA), tissue plasminogen
      activator (tPA), matrix metallopeptidases (MMPs), plasminogen activator inhibitor
      1 (PAI-1) and tissue inhibitor of metalloproteinases (TIMPs), and the cellular
      motility in PGE2-stimulated human LoVo cells. 17beta-Estradiol and the inhibitors
      including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580
      (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), QNZ (NFkappaB inhibitor) and
      ICI 182 780 were further used to explore the inhibitory effects of 17beta
      estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to
      analyze the difference between the two groups. RESULTS: Upregulation of urokinase
      plasminogen activator (uPA), tissue plasminogen activator (tPA) and matrix
      metallopeptidases (MMPs) is reported to associate with the development of cancer
      cell mobility, metastasis, and subsequent malignant tumor. After administration
      of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that
      PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling
      pathway, thus promoting cellular motility in human LoVo cancer cells. However,
      PGE2 treatment showed no effects on regulating expression of tPA, MMP-2,
      plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase
      1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that 17beta
      estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by
      suppressing activation of JNK1/2 in human LoVo cancer cells. CONCLUSIONS:
      Collectively, these results suggest that 17beta-estradiol treatment significantly
      inhibits PGE2-induced motility of human LoVo colon cancer cells.

PMID- 21859480
TI  - A nation-wide multicenter 10-year (1999-2008) retrospective clinical
      epidemiological study of female breast cancer in China.
AB  - BACKGROUND: According to the very limited cancer registry, incidence and
      mortality rates for female breast cancer in China are regarded to be increasing
      especially in the metropolitan areas. Representative data on the breast cancer
      profile of Chinese women and its time trend over years are relatively rare. The
      aims of the current study are to illustrate the breast cancer profile of Chinese
      women in time span and to explore the current treatment approaches to female
      breast cancer. METHODS: This was a hospital-based nation-wide and multi-center
      retrospective study of female primary breast cancer cases. China was divided into
      7 regions according to the geographic distribution; from each region, one
      tertiary hospital was selected. With the exception of January and February, one
      month was randomly selected to represent each year from year 1999 to 2008 at
      every hospital. All inpatient cases within the selected month were reviewed and
      related information was collected based on the designed case report form (CRF).
      The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was
      the leading hospital in this study. RESULTS: Four-thousand two-hundred and eleven
      cases were randomly selected from the total pool of 45,200 patients and were
      included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5
      yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common
      subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II
      accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty
      four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among
      them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine
      cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them
      were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211))
      was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less
      patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0%
      (1,599/4,211)). CONCLUSIONS: The younger age of breast cancer onset among Chinese
      women and more advanced tumor stages pose a great challenge. Adjuvant therapy,
      especially radiotherapy and endocrine therapy are of great unmet needs.

PMID- 21859481
TI  - Eccrine porocarcinoma of the lower extremity: a case report and review of
      literature.
AB  - Eccrine porocarcinoma is a rare malignancy of the eccrine sweat gland. It is
      usually found frequently on the lower extremities, and it affects both sexes
      equally usually in the sixth to seventh decade. In our case, we present a 42-year
      old male patient with a recurring exophytic tumor on the right lower extremity
      without local extension. The initial tumor was biopsied, excised and diagnosed as
      an eccrine poroma. The tumor then recurred 6 years later, was re-excised,
      reconstructed with a soleus muscle flap and diagnosed as an eccrine
      porocarcinoma.

PMID- 21859482
TI  - Integrated nanophotonic hubs based on ZnO-Tb(OH)3/SiO2 nanocomposites.
AB  - Optical integration is essential for practical application, but it remains
      unexplored for nanoscale devices. A newly designed nanocomposite based on ZnO
      semiconductor nanowires and Tb(OH)3/SiO2 core/shell nanospheres has been
      synthesized and studied. The unique sea urchin-type morphology, bright and
      sharply visible emission bands of lanthanide, and large aspect ratio of ZnO
      crystalline nanotips make this novel composite an excellent signal receiver,
      waveguide, and emitter. The multifunctional composite of ZnO nanotips and
      Tb(OH)3/SiO2 nanoparticles therefore can serve as an integrated nanophotonics
      hub. Moreover, the composite of ZnO nanotips deposited on a Tb(OH)3/SiO2 photonic
      crystal can act as a directional light fountain, in which the confined radiation
      from Tb ions inside the photonic crystal can be well guided and escape through
      the ZnO nanotips. Therefore, the output emission arising from Tb ions is truly
      directional, and its intensity can be greatly enhanced. With highly enhanced
      lasing emissions in ZnO-Tb(OH)3/SiO2 as well as SnO2-Tb(OH)3/SiO2 nanocomposites,
      we demonstrate that our approach is extremely beneficial for the creation of low
      threshold and high-power nanolaser.

PMID- 21859483
TI  - Substance use and its predictors among undergraduate medical students of Addis
      Ababa University in Ethiopia.
AB  - BACKGROUND: Substance use remains high among Ethiopian youth and young
      adolescents particularly in high schools and colleges. The use of alcohol, khat
      and tobacco by college and university students can be harmful; leading to
      decreased academic performance, increased risk of contracting HIV and other
      sexually transmitted diseases. However, the magnitude of substance use and the
      factors associated with it has not been investigated among medical students in
      the country. This study was conducted to determine the prevalence of substance
      use and identify factors that influenced the behavior among undergraduate medical
      students of Addis Ababa University in Ethiopia. METHODS: A cross-sectional study
      using a pre-tested structured self-administered quantitative questionnaire was
      conducted in June 2009 among 622 medical students (Year I to Internship program)
      at the School of Medicine. The data were entered into Epi Info version 6.04d and
      analyzed using SPSS version 15 software program. Descriptive statistics were used
      for data summarization and presentation. Differences in proportions were compared
      for significance using Chi Square test, with significance level set at p < 0.05.
      Multivariate logistic regression analyses were used to assess the magnitude of
      associations between substance use and socio-demographic and behavioral
      correlates. RESULTS: In the last 12 months, alcohol was consumed by 22% (25%
      males vs. 14% females, p = 0.002) and khat use was reported by 7% (9% males vs.
      1.5% females, p < 0.001) of the students. About 9% of the respondents (10.6%
      males vs. 4.6% females, p = 0.014) reported ever use of cigarette smoking, and
      1.8% were found to be current smokers. Using multiple logistic regression models,
      being male was strongly associated with alcohol use in the last 12 months
      (adjusted OR = 2.14, 95% CI = 1.22-3.76). Students whose friends currently
      consume alcohol were more likely to consume alcohol (adjusted OR = 2.47, 95% CI =
      1.50-4.08) and whose friends' use tobacco more likely to smoke (adjusted OR =
      3.89, 95% CI = 1.83-8.30). Khat use within the past 12 months was strongly and
      positively associated with alcohol consumption (adjusted OR = 15.11, 95% CI =
      4.24-53.91). Similarly, ever use of cigarette was also significantly associated
      with alcohol consumption (adjusted OR = 8.65, 95% CI = 3.48-21.50). CONCLUSIONS:
      Concordant use of alcohol, khat and tobacco is observed and exposure to friends'
      use of substances is often implicated. Alcohol consumption or khat use has been
      significantly associated with tobacco use. While the findings of this study
      suggest that substance use among the medical students was not alarming, but its
      trend increased among students from Year I to Internship program. The university
      must be vigilant in monitoring and educating the students about the consequences
      of substance use.

PMID- 21859484
TI  - Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing
      episodes in pre-school children.
AB  - BACKGROUND: Few data are available on the usefulness of short term treatment with
      low-medium dose of inhaled corticosteroids (ICS) in pre-school children with
      wheezing exacerbations. METHODS: To compare the efficacy of one week treatment
      with 400 MUg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized
      2500 MUg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus
      nebulized prn 2500 MUg salbutamol (placebo group), a post-hoc analysis was
      performed on data obtained in 166 pre-school children with multiple-trigger
      wheezing, recruited during an acute wheezing episode. RESULTS: The percentage of
      symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than
      in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by
      day analysis showed that the percentage of SFDs was already higher in the BDP
      group after 2 days (7.4%), the difference reaching statistical significance at
      day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as
      compared with the placebo group (0.39; p = 0.048), the difference reaching
      statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p
      = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in
      the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but
      the difference was not significant (p = 0.366). There were no differences in
      positive effects of BDP treatment between children with and without risk factors
      for asthma. CONCLUSIONS: A 1-week treatment with nebulized BDP and prn salbutamol
      is effective in increasing SFDs and improving cough in children with wheezing,
      providing a clinical rationale for the short term use of ICS in episodic wheeze
      exacerbations in pre-school children.

PMID- 21859485
TI  - Responsiveness of EORTC QLQ-C30, QLQ-CR38 and FACT-C quality of life
      questionnaires in patients with colorectal cancer.
AB  - BACKGROUND: The aim of this study was to compare the responsiveness of the
      European Organization for Research and Treatment (EORTC) quality of life
      questionnaires (QLQ-C30, QLQ-CR38) and the Functional Assessment of Cancer
      Therapy-colorectal version 4 questionnaire (FACT-C). METHOD: This prospective
      study included 127 patients with colorectal cancer: 71 undergoing chemotherapy
      and 56 radiation therapy. Responsiveness statistics included the Standardized
      Response Mean (SRM) and the Effect Size (ES). The patient's overall assessment of
      his/her change in state of health status was the reference criterion to evaluate
      the responsiveness of the QoL questionnaires. RESULTS: 34 patients perceived
      their health as stable and 17 as improved between the first and the fourth
      courses of chemotherapy. 21 patients perceived their health as stable and 22 as
      improved between before and the last week of radiotherapy.The responsiveness of
      the 3 questionnaires differed according to treatments. The EORTC QLQ-C30
      questionnaire was more responsive in patients receiving chemotherapy, particulary
      functional scales (SRM > 0.55). The QLQ-CR38 and the FACT-C questionnaires
      provided little clinically relevant information during chemotherapy or
      radiotherapy. CONCLUSION: The EORTC QLQ-C30 questionnaire appears to be more
      responsive in patients receiving chemotherapy.

PMID- 21859486
TI  - Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in
      sustentacular cells of mouse olfactory epithelium.
AB  - BACKGROUND: Extracellular nucleotides have long been known to play
      neuromodulatory roles and to be involved in intercellular signalling. In the
      olfactory system, ATP is released by olfactory neurons, and exogenous ATP can
      evoke an increase in intracellular calcium concentration in sustentacular cells,
      the nonneuronal supporting cells of the olfactory epithelium. Here we investigate
      the hypothesis that olfactory neurons communicate with sustentacular cells via
      extracellular ATP and purinergic receptor activation. RESULTS: Here we show that
      exposure of mice to a mixture of odorants induced a significant increase in the
      levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei
      of both olfactory sensory neurons and sustentacular cells. This activation was
      dependent on adenylyl cyclase III-mediated olfactory signaling and on activation
      of P2Y purinergic receptors on sustentacular cells. Purinergic receptor
      antagonists inhibited odorant-dependent CREB phosphorylation specifically in the
      nuclei of the sustentacular cells. CONCLUSION: Our results point to a possible
      role for extracellular nucleotides in mediating intercellular communication
      between the neurons and sustentacular cells of the olfactory epithelium in
      response to odorant exposure. Maintenance of extracellular ionic gradients and
      metabolism of noxious chemicals by sustentacular cells may therefore be regulated
      in an odorant-dependent manner by olfactory sensory neurons.

PMID- 21859487
TI  - The baseline pressure of intracranial pressure (ICP) sensors can be altered by
      electrostatic discharges.
AB  - BACKGROUND: The monitoring of intracranial pressure (ICP) has a crucial role in
      the surveillance of patients with brain injury. During long-term monitoring of
      ICP, we have seen spontaneous shifts in baseline pressure (ICP sensor zero
      point), which are of technical and not physiological origin. The aim of the
      present study was to explore whether or not baseline pressures of ICP sensors can
      be affected by electrostatics discharges (ESD's), when ESD's are delivered at
      clinically relevant magnitudes. METHODS: We performed bench-testing of a set of
      commercial ICP sensors. In our experimental setup, the ICP sensor was placed in a
      container with 0.9% NaCl solution. A test person was charged 0.5-10 kV, and then
      delivered ESD's to the sensor by touching a metal rod that was located in the
      container. The continuous pressure signals were recorded continuously
      before/after the ESD's, and the pressure readings were stored digitally using a
      computerized system RESULTS: A total of 57 sensors were tested, including 25
      Codman ICP sensors and 32 Raumedic sensors. When charging the test person in the
      range 0.5-10 kV, typically ESD's in the range 0.5-5 kV peak pulse were delivered
      to the ICP sensor. Alterations in baseline pressure >= 2 mmHg was seen in 24 of
      25 (96%) Codman sensors and in 17 of 32 (53%) Raumedic sensors. Lasting changes
      in baseline pressure > 10 mmHg that in the clinical setting would affect patient
      management, were seen frequently for both sensor types. The changes in baseline
      pressure were either characterized by sudden shifts or gradual drifts in baseline
      pressure. CONCLUSIONS: The baseline pressures of commercial solid ICP sensors can
      be altered by ESD's at discharge magnitudes that are clinically relevant. Shifts
      in baseline pressure change the ICP levels visualised to the physician on the
      monitor screen, and thereby reveal wrong ICP values, which likely represent a
      severe risk to the patient.

PMID- 21859488
TI  - The filter of choice: filtration method preference among injecting drug users.
AB  - BACKGROUND: Injection drug use syringe filters (IDUSF) are designed to prevent
      several complications related to the injection of drugs. Due to their small pore
      size, their use can reduce the solution's insoluble particle content and thus
      diminish the prevalence of phlebitis, talcosis.... Their low drug retention
      discourages from filter reuse and sharing and can thus prevent viral and
      microbial infections. In France, drug users have access to sterile cotton filters
      for 15 years and to an IDUSF (the Sterifilt(r)) for 5 years. This study was set
      up to explore the factors influencing filter preference amongst injecting drug
      users. METHODS: Quantitative and qualitative data were gathered through 241
      questionnaires and the participation of 23 people in focus groups. RESULTS:
      Factors found to significantly influence filter preference were duration and
      frequency of injecting drug use, the type of drugs injected and subculture.
      Furthermore, IDU's rationale for the preference of one type of filter over others
      was explored. It was found that filter preference depends on perceived health
      benefits (reduced harms, prevention of vein damage, protection of injection
      sites), drug retention (low retention: better high, protective mechanism against
      the reuse of filters; high retention: filter reuse as a protective mechanism
      against withdrawal), technical and practical issues (filter clogging, ease of
      use, time needed to prepare an injection) and believes (the conviction that a
      clear solution contains less active compound). CONCLUSION: It was concluded that
      the factors influencing filter preference are in favour of change; a shift
      towards the use of more efficient filters can be made through increased
      availability, information and demonstrations.

PMID- 21859490
TI  - Effect of growth hormone replacement therapy in a boy with Dent's disease: a case
      report.
AB  - INTRODUCTION: Dent's disease is an X-linked recessive proximal tubulopathy
      characterized by low molecular weight proteinuria, hypercalciuria,
      nephrocalcinosis, nephrolithiasis and progressive renal failure. To the best of
      our knowledge, this is only the third report on the use of growth hormone therapy
      in a child with poor growth associated with Dent's disease. CASE PRESENTATION: We
      report on a 7-year-old Montenegrin boy with proteinuria, hypercalciuria,
      nephrocalcinosis, rickets and short stature with unimpaired growth hormone
      secretion. A molecular genetic analysis showed S244L substitution on the CLCN5
      gene. After two years of conventional treatment with hydrochlorothiazide,
      laboratory tests revealed more prominent proteinuria, mild hypophosphatemia,
      increased values of alkaline phosphatase and features of rickets. Phosphate
      salts, calcitriol, potassium citrate and growth hormone were included in the
      therapy. After three years of therapy, his adjusted parental stature was 1.53
      standard deviations higher than at the initiation of growth hormone therapy. His
      global kidney functions and levels of proteinuria and calciuria remained
      relatively stable. In spite of the growth hormone therapy, his tubular
      reabsorption of phosphate deteriorated. CONCLUSION: Treatment with recombinant
      human growth hormone may have a positive effect on final height in poorly growing
      children with Dent's disease and hypophosphatemic rickets. However, it is not
      possible to reach definite conclusions due to the small sample within the
      literature and the brief duration of the therapy.

PMID- 21859489
TI  - Study protocol of cost-effectiveness and cost-utility of a biopsychosocial
      multidisciplinary intervention in the evolution of non-specific sub-acute low
      back pain in the working population: cluster randomised trial.
AB  - BACKGROUND: Low back pain (LBP), with high incidence and prevalence rate, is one
      of the most common reasons to consult the health system and is responsible for a
      significant amount of sick leave, leading to high health and social costs. The
      objective of the study is to assess the cost-effectiveness and cost-utility
      analysis of a multidisciplinary biopsychosocial educational group intervention
      (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the
      working population recruited in primary healthcare centres. METHODS/DESIGN: The
      study design is a cost-effectiveness and cost-utility analysis of a MBEGI in
      comparison with the usual care of non-specific sub-acute LBP.Measures on
      effectiveness and costs of both interventions will be obtained from a cluster
      randomised controlled clinical trial carried out in 38 Catalan primary health
      care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis
      of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical
      treatments, work sick leave (% and duration in days), Roland Morris disability,
      McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires.
      Utility measures will be calculated from the SF-12. The analysis will be
      performed from a social perspective. The temporal horizon is at 3 months (change
      to chronic LBP) and 12 months (evaluate the outcomes at long term).Assessment of
      outcomes will be blinded and will follow the intention-to-treat principle.
      DISCUSSION: We hope to demonstrate the cost-effectiveness and cost-utility of
      MBEGI, see an improvement in the patients' quality of life, achieve a reduction
      in the duration of episodes and the chronicity of non-specific low back pain, and
      be able to report a decrease in the social costs. If the intervention is cost
      effectiveness and cost-utility, it could be applied to Primary Health Care
      Centres. TRIAL REGISTRATION: ISRCTN: ISRCTN58719694.

PMID- 21859491
TI  - Retrosternal abscess after trigger point injections in a pregnant woman: a case
      report.
AB  - INTRODUCTION: Although retrosternal abscess is a well known complication of
      sternotomy and intravenous drug abuse, to date it has not been described as a
      consequence of trigger point injections. There are reported cases of serious
      complications as a result of this procedure including epidural abscess,
      necrotizing fasciitis, osteomyelitis and gas gangrene. CASE PRESENTATION: A 37
      year-old African-American woman, who was 20 weeks pregnant, presented to our
      emergency room with complaints of progressively worsening chest pain and
      shortness of breath over the course of the last two months. She was undergoing
      trigger point injections at multiple different sites including the
      sternoclavicular joint for chest pain and dystonia. Two years previously she had
      developed a left-sided pneumothorax as a result of this procedure, requiring
      chest tube placement and subsequent pleurodesis. Her vital signs in our emergency
      room were normal except for resting tachycardia, with a pulse of 100 beats per
      minute. A physical examination revealed swelling and tenderness of the sternal
      notch with tenderness to palpation over the left sternoclavicular joint.
      Laboratory data was significant for a white blood count of 13.3 * 109/L with 82%
      granulocytes. A chest radiograph revealed left basilar scarring with blunting of
      the left costophrenic angle. A computed tomography angiogram showed a 4.7 cm
      abscess in the retrosternal region behind the manubrium with associated sclerosis
      and cortical irregularity of the manubrium and left clavicle. CONCLUSION: Trigger
      point injection is generally considered very safe. However, there are reported
      cases of serious complications as a result of this procedure. A computed
      tomography scan of the chest should strongly be considered in the evaluation of
      chest pain and shortness of breath of unclear etiology in patients with even a
      remote history of trigger point injections.

PMID- 21859493
TI  - The stigma of obesity in the general public and its implications for public
      health - a systematic review.
AB  - BACKGROUND: Up to this date, prevalence rates of obesity are still rising. Aside
      from co-morbid diseases, perceived discrimination and stigmatization leads to
      worsen outcomes in obese individuals. Higher stigmatizing attitudes towards obese
      individuals may also result in less support of preventive and interventive
      measures. In light of the immense burden of obesity on health care systems and
      also on the individuals' quality of life, accepted and subsidized preventive
      measures are needed. Policy support might be determined by views of the lay
      public on causes of obesity and resulting weight stigma. This study seeks to
      answer how representative samples of the lay public perceive people with obesity
      or overweight status (stigmatizing attitudes); what these samples attribute
      obesity to (causal attribution) and what types of interventions are supported by
      the lay public and which factors determine that support (prevention support).
      METHODS: A systematic literature search was conducted. All studies of
      representative samples reporting results on (a) stigmatizing attitudes towards
      overweight and obese individuals, (b) causal beliefs and (c) prevention support
      were included. RESULTS: Only 7 articles were found. One study reported prevalence
      rates of stigmatizing attitudes. About a quarter of the population in Germany
      displayed definite stigmatizing attitudes. Other studies reported causal
      attributions. While external influences on weight are considered as well, it
      seems that internal factors are rated to be of higher importance. Across the
      studies found, regulative prevention is supported by about half of the
      population, while childhood prevention has highest approval rates. Results on
      sociodemographic determinants differ substantially. CONCLUSIONS: Further research
      on public attitudes toward and perception of overweight and obesity is urgently
      needed to depict the prevailing degree of stigmatization. Introducing a
      multidimensional concept of the etiology of obesity to the lay public might be a
      starting point in stigma reduction.

PMID- 21859494
TI  - Effect of iron oxide and gold nanoparticles on bacterial growth leading towards
      biological application.
AB  - BACKGROUND: Nanoparticle-metal oxide and gold represents a new class of important
      materials that are increasingly being developed for use in research and health
      related activities. The biological system being extremely critical requires the
      fundamental understanding on the influence of inorganic nanoparticles on cellular
      growth and functions. Our study was aimed to find out the effect of iron oxide
      (Fe3O4), gold (Au) nanoparticles on cellular growth of Escherichia coli (E. coli)
      and also try to channelize the obtained result by functionalizing the Au
      nanoparticle for further biological applications. RESULT: Fe3O4 and Au
      nanoparticles were prepared and characterized using Transmission electron
      microscopy (TEM) and Dynamic Light Scattering (DLS). Preliminary growth analysis
      data suggest that the nanoparticles of iron oxide have an inhibitory effect on E.
      coli in a concentration dependant manner, whereas the gold nanoparticle directly
      showed no such activity. However the phase contrast microscopic study clearly
      demonstrated that the effect of both Fe3O4 and Au nanoparticle extended up to the
      level of cell division which was evident as the abrupt increase in bacterial cell
      length. The incorporation of gold nanoparticle by bacterial cell was also
      observed during microscopic analysis based on which glutathione functionalized
      gold nanoparticle was prepared and used as a vector for plasmid DNA transport
      within bacterial cell. CONCLUSION: Altogether the study suggests that there is
      metal nanoparticle-bacteria interaction at the cellular level that can be
      utilized for beneficial biological application but significantly it also posses
      potential to produce ecotoxicity, challenging the ecofriendly nature of
      nanoparticles.

PMID- 21859492
TI  - Androgens as therapy for androgen receptor-positive castration-resistant prostate
      cancer.
AB  - Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in
      Western countries. While surgery is often successful for organ-confined prostate
      cancer, androgen ablation therapy is the primary treatment for metastatic
      prostate cancer. However, this therapy is associated with several undesired side
      effects, including increased risk of cardiovascular diseases. Shortening the
      period of androgen ablation therapy may benefit prostate cancer patients.
      Intermittent Androgen Deprivation therapy improves quality of life, reduces
      toxicity and medical costs, and delays disease progression in some patients. Cell
      culture and xenograft studies using androgen receptor (AR)-positive castration
      resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over
      expressing AR) suggest that androgens may suppress the growth of AR-rich prostate
      cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these
      cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of
      testosterone cause greater growth inhibition of relapsed tumors. Manipulating
      androgen/AR signaling may therefore be a potential therapy for AR-positive
      advanced prostate cancer.

PMID- 21859495
TI  - Adult Drosophila melanogaster evolved for antibacterial defense invest in
      infection-induced expression of both humoral and cellular immunity genes.
AB  - BACKGROUND: While the transcription of innate immunity genes in response to
      bacterial infection has been well-characterised in the Drosophila model, we
      recently demonstrated the capacity for such transcription to evolve in flies
      selected for improved antibacterial defense. Here we use this experimental system
      to examine how insects invest in constitutive versus infection-induced
      transcription of immunity genes. These two strategies carry with them different
      consequences with respect to energetic and pleiotropic costs and may be more or
      less effective in improving defense depending on whether the genes contribute to
      humoral or cellular aspects of immunity. FINDINGS: Contrary to expectation we
      show that selection preferentially increased the infection-induced expression of
      both cellular and humoral immunity genes. Given their functional roles, infection
      induced increases in expression were expected for the humoral genes, while
      increases in constitutive expression were expected for the cellular genes. We
      also report a restricted ability to improve transcription of immunity genes that
      is on the order of 2-3 fold regardless of total transcription level of the gene.
      CONCLUSIONS: The evolved increases in infection-induced expression of the
      cellular genes may result from specific cross talk with humoral pathways or from
      generalised strategies for enhancing immunity gene transcription. A failure to
      see improvements in constitutive expression of the cellular genes suggests either
      that increases might come at too great a cost or that patterns of expression in
      adults are decoupled from the larval phase where increases would be most
      effective. The similarity in fold change increase across all immunity genes may
      suggest a shared mechanism for the evolution of increased transcription in small,
      discrete units such as duplication of cis-regulatory elements.

PMID- 21859496
TI  - Genetic polymorphism of ACE and the angiotensin II type1 receptor genes in
      children with chronic kidney disease.
AB  - AIM AND METHODS: We investigated the association between polymorphisms of the
      angiotensin converting enzyme-1 (ACE-1) and angiotensin II type one receptor
      (AT1RA1166C) genes and the causation of renal disease in 76 advanced chronic
      kidney disease (CKD) pediatric patients undergoing maintenance hemodialysis (MHD)
      or conservative treatment (CT). Serum ACE activity and creatine kinase-MB
      fraction (CK-MB) were measured in all groups. Left ventricular mass index (LVMI)
      was calculated according to echocardiographic measurements. Seventy healthy
      controls were also genotyped. RESULTS: The differences of D allele and DI
      genotype of ACE were found significant between MHD group and the controls (p =
      0.0001). ACE-activity and LVMI were higher in MHD, while CK-MB was higher in CT
      patients than in all other groups. The combined genotype DD v/s ID+II comparison
      validated that DD genotype was a high risk genotype for hypertension .~89% of the
      DD CKD patients were found hypertensive in comparison to ~ 61% of patients of non
      DD genotype(p = 0.02). The MHD group showed an increased frequency of the C
      allele and CC genotype of the AT1RA1166C polymorphism (P = 0.0001). On multiple
      linear regression analysis, C-allele was independently associated with
      hypertension (P = 0.04). CONCLUSION: ACE DD and AT1R A/C genotypes implicated
      possible roles in the hypertensive state and in renal damage among children with
      ESRD. This result might be useful in planning therapeutic strategies for
      individual patients.

PMID- 21859498
TI  - BMP-2 gene-fibronectin-apatite composite layer enhances bone formation.
AB  - BACKGROUND: Safe and efficient gene transfer systems are needed for tissue
      engineering. We have developed an apatite composite layer including the bone
      morphogenetic protein-2 (BMP-2) gene and fibronectin (FB), and we evaluated its
      ability to induce bone formation. METHODS: An apatite composite layer was
      evaluated to determine the efficiency of gene transfer to cells cultured on it.
      Cells were cultured on a composite layer including the BMP-2 gene and FB, and BMP
      2 gene expression, BMP-2 protein concentrations, alkaline phosphatase (ALP)
      activity, and osteocalcin (OC) concentrations were measured. A bone defect on the
      cranium of rats was treated with hydroxyapatite (HAP)-coated ceramic buttons with
      the apatite composite layer including the BMP-2 gene and FB (HAP-BMP-FB). The
      tissue concentration of BMP-2, bone formation, and the expression levels of the
      BMP-2, ALP, and OC genes were all quantified. RESULTS: The apatite composite
      layer provided more efficient gene transfer for the cultured cells than an
      apatite composite layer without FB. The BMP-2 concentration was approximately 100
      600 pg/mL in the cell-culture medium. Culturing the cells on the apatite
      composite layer for 27 days increased ALP activity and OC concentrations. In
      animal experiments, the tissue concentrations of BMP-2 were over 100 pg/mg in the
      HAP-BMP-FB group and approximately 50 pg/mg in the control groups. Eight weeks
      later, bone formation was more enhanced in the HAP-BMP-FB group than in the
      control groups. In the tissues surrounding the HAP button, the gene expression
      levels of ALP and OC increased. CONCLUSION: The BMP-2 gene-FB-apatite composite
      layer might be useful for bone engineering.

PMID- 21859499
TI  - Trends in beliefs about the harmfulness and use of stop-smoking medications and
      smokeless tobacco products among cigarettes smokers: Findings from the ITC four
      country survey.
AB  - BACKGROUND: Evidence shows that smokers are generally misinformed about the
      relative harmfulness of nicotine, and smokeless forms of nicotine delivery in
      relation to smoked tobacco. This study explores changing trends in the beliefs
      about the harmfulness and use of stop smoking medications and smokeless tobacco
      in adult smokers in four countries where public education and access to
      alternative forms of nicotine is varied (Canada, the US, the UK and Australia).
      METHODS: Data are from seven waves of the ITC-4 country study conducted between
      2002 and 2009 with adult smokers from Canada, the US, the UK and Australia. For
      the purposes of this study, data were collected from 21,207 current smokers.
      Using generalised estimating equations to control for multiple response sets,
      multivariate models were tested to look for main effects of country, and trends
      across time, controlling for demographic variables. RESULTS: Knowledge remained
      low in all countries, although UK smokers tended to be better informed. There was
      a small but significant improvement across time in the UK, but mixed effects in
      the other three countries. At the final wave, between 37.5% (US) and 61.4% (UK)
      reported that NRT is a lot less harmful than cigarettes. In Canada and the US,
      where smokeless tobacco is marketed, only around one in six believed some
      smokeless tobacco products could be less harmful than cigarettes. CONCLUSIONS:
      Many smokers continue to be misinformed about the relative safety of nicotine and
      alternatives to smoked tobacco, especially in the US and Canada. Concerted
      efforts to educate UK smokers have probably improved their knowledge. Further
      research is required to assess whether misinformation deters smokers from
      appropriate use of alternative forms of nicotine.

PMID- 21859497
TI  - Potential applications of curcumin and its novel synthetic analogs and
      nanotechnology-based formulations in cancer prevention and therapy.
AB  - Curcumin has attracted great attention in the therapeutic arsenal in clinical
      oncology due to its chemopreventive, antitumoral, radiosensibilizing and
      chemosensibilizing activities against various types of aggressive and recurrent
      cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain
      cancer, melanoma and skin, lung, prostate, breast, ovarian, liver,
      gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates
      its anti-proliferative, anti-invasive and apoptotic effects on cancer cells,
      including cancer stem/progenitor cells and their progenies, through multiple
      molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the
      members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog
      (SHH)/GLIs and Wnt/beta-catenin and downstream signaling elements such as Akt,
      nuclear factor-kappa B (NF-kappaB) and signal transducers and activators of
      transcription (STATs). In counterbalance, the high metabolic instability and poor
      systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of
      great therapeutic interest, the selective delivery of synthetic analogs or
      nanotechnology-based formulations of curcumin to tumors, alone or in combination
      with other anticancer drugs, may improve their chemopreventive and
      chemotherapeutic efficacies against cancer progression and relapse. Novel
      curcumin formulations may also be used to reverse drug resistance, eradicate the
      total cancer cell mass and improve the anticarcinogenic efficacy of the current
      anti-hormonal and chemotherapeutic treatments for patients with various
      aggressive and lethal cancers.

PMID- 21859500
TI  - Assessing awareness of colorectal cancer symptoms: measure development and
      results from a population survey in the UK.
AB  - BACKGROUND: This paper describes the development of a Cancer Awareness Measure
      for colorectal (CRC) cancer (Bowel/Colorectal CAMa) (study 1) and presents key
      results from a population-representative survey using the measure (study 2).
      METHODS: STUDY 1: Items were taken from the literature and reviewed by expert
      groups. A series of three validation studies assessed reliability and validity of
      the measure. To establish test-retest reliability, 49 people over 50 years of age
      completed the Bowel/Colorectal CAM on two occasions (range 9-14 days, mean 13.5
      days). Construct validity was assessed by comparing responses from bowel cancer
      experts (n = 16) and the lay public (n = 35). Lastly, a brief intervention study
      tested sensitivity to change with participants (n = 70) randomly allocated to be
      given a control leaflet or an intervention leaflet and their responses were
      compared. STUDY 2: 1520 respondents completed the Bowel/Colorectal CAM in a
      population survey carried out by TNS-British Market Research Bureau International
      (TNS-BMRB) in March 2010. RESULTS: STUDY 1: Internal reliability (Cronbach's
      alpha = 0.84) was high. Test-retest reliability was over r = 0.7 for warning
      signs, risk factors and age people are first invited for screening, but lower
      (between 0.6 and 0.7) for other items (lifetime risk, awareness of bowel cancer
      screening, age at risk). Bowel cancer experts achieved higher scores than equally
      educated controls (54.7 [4.3] vs. 42.9 [5.7]; P < 0.001) demonstrating the
      measure has construct validity and intervention participants showed higher
      knowledge than controls (51.4 [5.9] vs. 42.9 [5.7]; P < 0.001) suggesting the
      measure is sensitive to change. STUDY 2: Respondents recalled on average, one CRC
      sign and one risk factor. There was particularly low prompted awareness of the
      signs 'lump in the abdomen' (64%) and 'tiredness' (50%) and several lifestyle
      risk factors for CRC, e.g. exercise (37%).Respondents from more affluent groups
      had consistently higher knowledge of signs and risk factors compared to those
      from more deprived groups. CONCLUSIONS: The Bowel/Colorectal CAM meets accepted
      psychometric criteria for reliability and construct validity and should therefore
      provide a useful tool for assessment of CRC awareness. The population survey
      revealed low awareness of several CRC signs and risk factors and emphasises the
      importance of continuing public education, particularly about the link between
      lifestyle behaviours and CRC.

PMID- 21859501
TI  - Does selection or genetic drift explain geographic differentiation of
      morphological characters in house sparrows Passer domesticus?
AB  - Understanding the relative influence of genetic drift and selection is
      fundamental in evolutionary biology. The theory of neutrality predicts that the
      genetic differentiation of a quantitative trait (QST) equals the genetic
      differentiation at neutral molecular markers (FST) if the quantitative trait has
      not been under selection. Thus, the relative magnitude of observed QST and
      expected QST under neutral expectations suggests the importance of selection and
      genetic drift for any observed phenotypic divergence. Because QST is based on
      additive genetic variance, estimating QST based on phenotypic measurements is
      problematic due to unknown environmental effects. To account for this, we used a
      model where the environmental component was allowed to vary when estimating QST.
      The model was used on data from 14 house sparrow (Passer domesticus) populations
      in Norway. In accordance with the significant phenotypic inter-population
      differences our analyses suggested that directional selection may have favoured
      different optimal phenotypes for some morphological traits across populations. In
      particular, different body mass and male ornamental phenotypes seemed to have
      been favoured. The conclusions are, however, dependent on assumptions regarding
      the proportion of the observed inter-population variation that is due to additive
      genetic differences, showing the importance of collecting such information in
      natural populations. By estimating QST, allowing the additive genetic proportion
      of phenotypic inter-population variation to vary, and by making use of recent
      statistical methods to compare observed QST with neutral expectations, we can use
      data that are relatively easy to collect to identify adaptive variation in
      natural populations.

PMID- 21859502
TI  - Transmission and control in an institutional pandemic influenza A(H1N1) 2009
      outbreak.
AB  - A pandemic influenza A(H1N1) 2009 outbreak in a summer school affected 117/276
      (42%) students. Residential social contact was associated with risk of infection,
      and there was no evidence for transmission associated with the classroom setting.
      Although the summer school had new admissions each week, which provided
      susceptible students the outbreak was controlled using routine infection control
      measures (isolation of cases, basic hygiene measures and avoidance of
      particularly high-risk social events) and prompt treatment of cases. This was in
      the absence of chemoprophylaxis or vaccination and without altering the basic
      educational activities of the school. Modelling of the outbreak allowed
      estimation of the impact of interventions on transmission. These models and
      follow-up surveillance supported the effectiveness of routine infection control
      measures to stop the spread of influenza even in this high-risk setting for
      transmission.

PMID- 21859503
TI  - Intestinal parasitic infections in an industrialized country; a new focus on
      children with better DNA-based diagnostics.
AB  - In recent years, the isolation of parasitic DNA from faecal samples and PCR
      techniques, have been improved and simplified. Moreover, the introduction of real
      time PCR has made it possible to multiplex different targets into one reaction.
      These new technical possibilities make it feasible to introduce PCR with its
      unsurpassed sensitivity and specificity in a routine laboratory setting for the
      diagnosis of intestinal parasites. Detection rates of the parasitic infections
      included in the PCR are increased significantly compared with microscopy.
      Molecular diagnostics, especially in children, reveal a possible cause of the
      gastrointestinal complaints in many more cases compared with conventional
      methods. Usually in GP patients no other pathogenic parasites are detected using
      microscopy and in the returning travellers additional parasites are found with
      microscopy in a minority of cases only. Multiplex real-time PCR offers a highly
      sensitive and specific diagnostic alternative for labour intensive microscopy in
      clinical laboratory practice. Additional diagnostic methods for the detection of
      parasitic infections that are not included as PCR target can be limited to a
      selected group of patients.

PMID- 21859504
TI  - Improving food provision in child care in England: a stakeholder analysis.
AB  - OBJECTIVE: To review national policy governing nutrition in child-care settings
      and explore policy translation at a regional and local level in the South East of
      England. DESIGN: Semi-structured interviews with regional experts. SETTING: Child
      care settings in Southampton, England, registered by OFSTED (Office for Standards
      in Education Children's Services and Skills). SUBJECTS: Thirteen subjects
      including child-care professionals in Southampton and policy advisors from the
      Government Office of the South East. RESULTS: Policy regarding early years food
      provision varies across the country. Although there appears to be consensus
      between local stakeholders on the importance of improving early years nutrition
      in Southampton, intentions have yet to be translated into cohesive action, with
      differences in food and nutrition practice in child-care settings across the
      city. There are also areas of incoherence, inequalities in access to training and
      development, and duplication in local and regional support mechanisms.
      CONCLUSIONS: The importance of proper early nutrition to provide the building
      blocks for life-long health and well-being is grounded in a substantial evidence
      base. Outside the home, early years child-care settings are an ideal place for
      providing a strong foundation in nutritional health and dietary habits for young
      children. The long-term benefits of achieving optimum nutrition in the early
      years should be secured through the coherent efforts of national, regional and
      local policy makers, child-care practitioners and parents. Existing commitment
      and capacity to achieve this objective at a local and regional level must be
      supported and matched at a national level with the acceleration of policy
      development, including quality control and support mechanisms.

PMID- 21859505
TI  - A cost-effectiveness study of the community-based intervention '10 000 Steps
      Ghent'.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of the European community-based
      project '10 000 Steps Ghent', an intervention that resulted in a significant
      decrease in sedentary time and a significant increase in step counts (896
      steps/d) and self-reported walking (66 min/week). DESIGN: An age- and gender
      dependent Markov model, with a time horizon of 20 years and a cycle length of 1
      year, estimating the development of diabetes, cardiovascular events and
      colorectal cancer. SETTING: All individuals started in a health state free of
      events. The effect of the intervention was based on published risk reductions
      related to increased walking time. Costs and utility decrements related to events
      were obtained from published literature. The impact of the uncertainty of the
      parameters on incremental costs and quality-adjusted life years (QALY) were
      assessed with one-way sensitivity analyses and a Monte Carlo analysis. SUBJECTS:
      Cohort representing the population reached by the intervention (266 adults aged
      25-75 years with a mean age of 48.2 (sd 13.1) years, 45.6 % men, 64.6 % highly
      educated, 70.0 % employed). RESULTS: Implementing the community-based programme
      increased average QALY by 0.16 and 0.11 for men and women, respectively. The
      total costs decreased by approximately 576? and 427?, respectively. Hence, for
      both genders the intervention programme was dominant. The sensitivity analyses
      did not change the conclusion of dominance. CONCLUSION: The community-based '10
      000 Steps Ghent' campaign is a dominant intervention. Sensitivity analyses have
      proved the robustness of the results; hence implementing this intervention on a
      population-based level could lead to improved health outcomes and reduced costs.

PMID- 21859506
TI  - Nutrition signposting: the 'eat more' message is getting through; what about the
      'eat less' message?

PMID- 21859507
TI  - Socio-economic inequalities in overweight among adults in Turkey: a regional
      evaluation.
AB  - OBJECTIVE: Patterns of socio-economic inequalities in obesity and overweight have
      not been documented for Turkey. The present study aimed to describe educational
      and wealth-related inequalities for overweight in Turkey, taking a regional
      perspective. DESIGN: Cross-sectional self-reported data of the World Health
      Survey 2002 for Turkey were used. BMI >= 25.00 kg/m2 was considered as
      overweight. Respondents were classified according to education years and a wealth
      score derived from the availability of household assets. Logistic regression
      analysis was applied to assess the relationship between overweight and socio
      economic factors. Analyses were stratified by sex and region (West,
      Mediterranean, Middle, Black Sea and East). SETTING: Turkey. SUBJECTS: Among the
      respondents 20 years and older, 3790 women and 4057 men had data on self-reported
      height and weight. RESULTS: Age-adjusted overweight prevalence was 48.4 % for
      women and 46.1 % for men. For men, education was not systematically related to
      overweight while overweight was significantly increased among the highest wealth
      groups. For women, the prevalence of overweight was highest for low-educated and
      middle-wealth groups. The size of the inequalities in overweight showed only
      small regional variations. In the East, however, overweight prevalence was more
      related to higher socio-economic position than in the other regions. CONCLUSIONS:
      Socio-economic inequalities for overweight in Turkey are at a similar level as in
      most European countries, and especially comparable to Southern Europe. The
      smaller inequalities in the East correspond to the low level of socio-economic
      development in this part of the country. Prevention of overweight should focus on
      lower educational groups throughout the entire country and especially on low
      educated women.

PMID- 21859508
TI  - Prolonged breast-feeding protects mothers from later-life obesity and related
      cardio-metabolic disorders.
AB  - OBJECTIVE: To investigate the long-term effects of duration of postpartum
      lactation on maternal body composition and risk for cardio-metabolic disorders in
      later life. DESIGN: Retrospective study. Body composition was measured using dual
      energy X-ray absorptiometry and serum glucose, insulin and lipids were analysed
      using enzymatic photometric methods 16-20 years after the last pregnancy. Medical
      history and lifestyle factors were collected via a self-administered
      questionnaire. Detailed information regarding weight change patterns during each
      pregnancy was obtained from personal maternity tracking records. SETTING: City of
      Jyvaskyla and surroundings in Central Finland. SUBJECTS: Two hundred and twelve
      women (mean age 48, range 36-60 years). RESULTS: At 16-20 years after their last
      pregnancy, women who had breast-fed for less than 6 months had higher total body
      fat mass and fat mass percentage, particularly in the android region (46.5 (sd
      8.2) %) than mothers who had breast-fed for longer than 6 months (39.0 (sd 10.2)
      %) or for longer than 10 months (38.4 (sd 10.9) %, P < 0.01). These differences
      were independent of pre-pregnancy weight and BMI, menopausal status, smoking
      status, level of education, participation in past and present leisure-time
      physical activity, and current dietary energy intake. Higher body fat mass was
      also associated with higher fasting serum glucose concentration and insulin
      resistance, TAG, LDL cholesterol and total cholesterol concentrations, as well as
      higher systolic and diastolic blood pressure (P < 0.05 for all). CONCLUSIONS:
      Short duration of breast-feeding may induce weight retention and fat mass
      accumulation, resulting in increased risk of cardio-metabolic disorders in later
      life.

PMID- 21859509
TI  - Serum retinol in 1-6-year-old children from a low socio-economic South African
      community with a high intake of liver: implications for blanket vitamin A
      supplementation.
AB  - OBJECTIVE: To assess serum retinol, liver intake patterns, breast-feeding history
      and anthropometric status in pre-school children of a low socio-economic
      community where liver is regularly consumed. DESIGN: Cross-sectional study.
      SETTING: Northern Cape Province, South Africa. SUBJECTS: Children aged 1-6 years
      (n 243) who attended the local primary health-care facility and had not received
      a vitamin A supplement in the 6 months preceding the study. Non-pregnant female
      caregivers (n 225), below 50 years of age, were also assessed. RESULTS: Despite
      stunting, underweight and wasting being prevalent in 40.5%, 23.1% and 8.4% of the
      children, only 5.8% had serum retinol concentrations < 20 MUg/dl, which is in
      sharp contrast to the national prevalence of 63.6%. None of the caregivers were
      vitamin A deficient. Liver was eaten by 89.2% of children, with 87% of households
      eating liver at least once monthly and 30% eating it at least once weekly; liver
      was introduced into the diet of the children at a median age of 18 months. Ninety
      three per cent of the children were being breast-fed or had been breast-fed in
      the past; children were breast-fed to a median age of 18 months. A significant
      negative correlation was found between educational level of the caregiver and
      frequency of liver intake (r = -0.143, P=0.032). There was no correlation between
      serum retinol and indicators of anthropometric or socio-economic status.
      CONCLUSIONS: The blanket approach in applying the national vitamin A
      supplementation programme may not be appropriate for all areas in the country,
      even though the community may be poor and undernourished.

PMID- 21859510
TI  - Urban v. suburban perceptions of the neighbourhood food environment as correlates
      of adolescent food purchasing.
AB  - OBJECTIVE: To assess the relationship between adolescent perception of time to
      walk to neighbourhood food retail outlets and purchasing of sugar-sweetened
      beverages (SSB), fast and convenience food items, and to test for differences by
      urban v. suburban environment. DESIGN: Cross-sectional observational study.
      SETTING: Twin Cities Metropolitan Area, Minnesota, USA. SUBJECTS: Adolescents
      from two studies completed survey-based measures on perceptions of time to walk
      to food retail outlets from home, purchasing patterns of SSB and fast and
      convenience store items, perceptions of personal safety and pedestrian
      infrastructure, and demographic characteristics. Descriptive analysis, Spearman
      correlations and multivariate linear regression, accounting for clustering, were
      conducted. RESULTS: There were 634 adolescents, approximately half male,
      predominantly white, with a middle-class background. Greater perceived time to
      food outlets was associated with less frequent purchasing of SSB, convenience
      store foods and fast-food items. Multivariate models showed that a perceived
      shorter walking time (i.e. 1-5 v. 31+ min) was significantly associated with more
      SSB purchasing. SSB purchases were also significantly associated with the number
      of food outlets within a 10 min walk (B = 0.05, P = 0.02). CONCLUSIONS: A
      reduction in consumption of SSB and other energy-dense snacks is an important
      obesity prevention approach. An approach offering alternatives or reducing
      exposure in addition to education to alter purchasing habits may contribute to
      improving dietary habits and reducing the obesity epidemic.

PMID- 21859511
TI  - The public health nutrition intervention management bi-cycle: a model for
      training and practice improvement.
AB  - OBJECTIVE: The present paper describes a model for public health nutrition
      practice designed to facilitate practice improvement and provide a step-wise
      approach to assist with workforce development. DESIGN: The bi-cycle model for
      public health nutrition practice has been developed based on existing cyclical
      models for intervention management but modified to integrate discrete capacity
      building practices. SETTING: Education and practice settings. SUBJECTS: This
      model will have applications for educators and practitioners. RESULTS:
      Modifications to existing models have been informed by the authors' observations
      and experiences as practitioners and educators, and reflect a conceptual
      framework with applications in workforce development and practice improvement.
      From a workforce development and educational perspective, the model is designed
      to reflect adult learning principles, exposing students to experiential, problem
      solving and practical learning experiences that reflect the realities of work as
      a public health nutritionist. In doing so, it assists the development of
      competency beyond knowing to knowing how, showing how and doing. This progression
      of learning from knowledge to performance is critical to effective competency
      development for effective practice. CONCLUSIONS: Public health nutrition practice
      is dynamic and varied, and models need to be adaptable and applicable to practice
      context to have utility. The paper serves to stimulate debate in the public
      health nutrition community, to encourage critical feedback about the validity,
      applicability and utility of this model in different practice contexts.

PMID- 21859512
TI  - Exploring school and home food environments: perceptions of 8-10-year-olds and
      their parents in Newcastle upon Tyne, UK.
AB  - OBJECTIVE: To use an innovative mixed-method approach to analyse and describe 8
      10-year-olds' home and school food environments. DESIGN: A mixed-method approach
      to collect qualitative and quantitative data was used, in which pupils took
      photographs over four days to record their food intake and food environment. The
      photographs were discussed in focus groups. A combination of lunchtime
      observations and questionnaires completed by parents were used to build up a
      picture of the children's home and school food environments. SETTING: A primary
      school in a suburb of Newcastle upon Tyne, UK. SUBJECTS: Twenty-seven children
      aged 8-10 years consented to take part in the study. Twenty-four returned
      cameras, and eighteen parents completed questionnaires. RESULTS: Photographs
      illustrated a range of locations throughout the home where children consumed
      food. Children's photographs revealed they ate less often with family and more
      often in front of the television than reported in parental questionnaires.
      Emergent themes during focus group discussions revealed a strong preference for
      packed lunches and dissatisfaction with school dinners. In this small sample,
      children's eating habits and preferences showed few associations with either
      gender or the deprivation level of the area in which they lived. CONCLUSIONS: The
      children's home food environments showed a great deal of variation, with parents
      being key moderators of food availability and consumption. While the school's
      food provisions met national nutritional standards, the social aspects of having
      a packed lunch appeared to be a positive aspect of eating at school.

PMID- 21859513
TI  - Impact of awareness of the Japanese Food Guide Spinning Top on eating behaviour.
AB  - OBJECTIVE: To investigate whether awareness of the Japanese Food Guide (JFG) can
      promote changes in eating behaviour. DESIGN: A longitudinal study was conducted
      in 2007 and 2009 by means of an Internet-based survey. Awareness status of the
      JFG and a sixteen-item scale for calculating eating behaviour scores were
      obtained. SETTING: Japan. SUBJECTS: In total, 787 Japanese adults (20-59 years)
      who registered with an Internet research service organization were included in
      the study. The respondents were divided into three groups. The respondents who
      were aware of the JFG in 2007 were categorized into Group 1. Those who were not
      aware of the JFG in 2007 were categorized into either Group 2 or Group 3. Group 2
      became aware of the JFG by 2009, and Group 3 was not aware of the JFG in 2009.
      RESULTS: In Group 2, the eating behaviour score increased significantly by 0.8
      points from 4.7 in 2007 to 5.5 in 2009 (P = 0.004). The eating behaviour score of
      Group 1 (6.5 points in 2007; 6.3 points in 2009) and Group 3 (3.8 points in 2007;
      4.1 points in 2009) did not change significantly from 2007 to 2009. CONCLUSIONS:
      Awareness of the JFG promoted eating behaviour change in the Japanese population.
      The results indicate that awareness of nutrition information from sources such as
      the JFG would promote healthy eating.

PMID- 21859514
TI  - Efficacy of agomelatine in major depressive disorder: meta-analysis and
      appraisal.
AB  - Agomelatine is the first approved antidepressant that mediates its activity
      through the melatoninergic pathway rather than the monoaminergic system. This
      meta-analysis aims to summarize an up-to-date report on the efficacy of
      agomelatine in major depressive disorder. Archives of published results in
      PubMed, CINAHL, Cochrane Library, EMBASE and PsycINFO databases were searched for
      randomized double-blind trials comparing agomelatine against placebo or
      antidepressant in major depressive disorder. Change in severity of depression as
      a result of intervention was the main outcome measure. Data necessary to compute
      the standardized mean difference (SMD) of this outcome and additional sample
      parameters that were likely to influence the main outcome were extracted for each
      selected studies. Summary effect sizes of various groups and subgroups were
      computed from SMDs between agomelatine and control (placebo or antidepressants)
      arms. There were nine trials involving 3943 severe cases of depression on
      agomelatine (n=2390) and either placebo (n=689) or antidepressants (n=864).
      Agomelatine (n=1274) stood superior to placebo (n=689) by a small margin (SMD 
      0.26, p=3.48*10-11) and the superiority of agomelatine (n=834, dose >= 25 mg/d)
      over antidepressants (paroxetine, fluoxetine, sertraline, venlafaxine; n=864) was
      even smaller (SMD -0.11, p=0.02). Although there is evidence of the superiority
      of agomelatine over placebo and selected antidepressants, it is questionable
      whether the magnitude of effect size is clinically significant and sample
      characteristics are relevant to the general patient population with major
      depressive disorder.

PMID- 21859515
TI  - Electroacupuncture reverses ethanol-induced locomotor sensitization and
      subsequent pERK expression in mice.
AB  - Extracellular signal-regulated kinase (ERK) plays a role in neuronal changes
      induced by repeated drug exposure. Given that electroacupuncture reverses
      locomotor sensitization induced by ethanol, we investigated whether this effect
      is parallel to ERK signalling. Mice received daily ethanol (2 g/kg i.p), for 21
      d. Electroacupuncture was performed daily, during four (subsequent) days of
      ethanol withdrawal. The stimulus of 2 Hz or 100 Hz was provided in combinations
      of two acupoints: Ea1 (ST-36/Zusanli and PC-6/Neiguan) or Ea2 (Du-14/Dazhui and
      Du-20/Baihui). The specificity of acupoint effects were assessed by the inclusion
      of additional groups: Ea3 (ST-25/Tianshu--acupoint used for other non-related
      disorders), Sham1 or Sham2 (transdermic stimulation near the respective
      acupoints). The control group was only handled during withdrawal and the saline
      group was chronically treated with saline and handled similarly to controls. At
      day 5 of withdrawal, each group was divided in two subgroups, according to the
      presence or absence of ethanol challenge. The animals were perfused and their
      brains processed for pERK immunohistochemistry. Only Ea1 at 100 Hz (Ea1_100) and
      Ea2 at 2 Hz (Ea2_2) reversed locomotor sensitization induced by ethanol. Ethanol
      withdrawal decreases pERK in the dorsomedial striatum. This decrease is not
      abolished by electroacupuncture. Conversely, ethanol challenge increases pERK in
      the dorsomedial striatum, infralimbic cortex and central nucleus of amygdala. The
      specificity of acupoint stimulation to reverse these increases was seen only for
      Ea2_2, in the infralimbic cortex and dorsomedial striatum. Therefore, behavioural
      effects of Ea2_2 (but not Ea1_100) depend, at least in part, on ERK signalling.

PMID- 21859516
TI  - Positive impact of a pre-school-based nutritional intervention on children's
      fruit and vegetable intake: results of a cluster-randomized trial.
AB  - OBJECTIVE: To assess the short-term impact of a nutritional intervention aimed at
      reducing childhood overweight in German pre-school children. DESIGN: Using a
      cluster-randomized study design with waiting-list controls, we tested a 6-month
      intervention administered once weekly by a nutrition expert consisting of joint
      meal preparation and activities for children and parents such as tasting and
      preparing nutritious, fresh foods. At baseline, 6 and 12 months, a parent
      completed questionnaire assessed fruit and vegetable intakes (primary outcomes)
      and water and sugared drinks consumption (secondary outcomes). Direct measurement
      assessed BMI, skinfold thickness and waist-to-height-ratio. An intention-to-treat
      analysis used random-effects panel regression models to assess the intervention
      effect, adjusted for each child's age, gender, immigrant background and maternal
      education. SETTING: Eighteen pre-schools from three south German regions.
      SUBJECTS: Healthy children aged 3-6 years. RESULTS: Three hundred and seventy
      seven (80 %) eligible pre-school children participated in the study. Of these,
      348 provided sufficient data for analysis. The sample mean age was 4.26 (sd 0.78)
      years; the majority (53.2 %) were boys. Children's fruit and vegetable intakes
      increased significantly (P < 0.001 and P < 0.05, respectively); no significant
      changes in the consumption of water, sugared drinks or anthropometric
      measurements were noted. CONCLUSIONS: Nutritional interventions in pre-schools
      have the potential to change eating behaviours in young children, which in the
      long term might reduce risk for developing overweight.

PMID- 21859517
TI  - Validity of two short screeners for diet quality in time-limited settings.
AB  - OBJECTIVE: An urgent need in dietary assessment is the development of short tools
      that provide valid assessments of dietary quality for use in time-limited
      settings. The present study assessed concurrent and construct validity of the
      short Diet Quality Screener (sDQS) and brief Mediterranean Diet Screener (bMDSC)
      questionnaires. DESIGN: Relative validity was measured by comparing three dietary
      quality indices--the Diet Quality Index (DQI), the modified Mediterranean Diet
      Score (mMDS) and the Antioxidant Score (ANTOX-S)--derived from the two
      questionnaires with those from multiple 24 h recalls over 12 months. Construct
      validity was demonstrated by correlations between average nutrient intake
      recorded on multiple 24 h recalls and the DQI, mMDS and ANTOX-S derived by the
      short screeners. SETTING: Both short questionnaires were administered to 102
      participants recruited from a population-based survey in Spain. RESULTS: DQI,
      mMDS and ANTOX-S correlated (P < 0.001) with the corresponding 24 h recall
      indices (r = 0.61, 0.40 and 0.45, respectively). Limits of agreement lay between
      96 and 126%, 59 and 144% and 61 and 118% for the DQI, ANTOX-S and mMDS,
      respectively. Dietary intakes of fibre, vitamin C, vitamin E, Mg and K reported
      on the 24 h recalls were positively associated (P < 0.04) with the DQI, mMDS and
      ANTOX-S indices. CONCLUSIONS: The sDQS and bMDSC provide reasonable
      approximations to food-based dietary indices and accurately situate subjects
      within the indices constructed for the present validation study.

PMID- 21859518
TI  - Synthesis and in vitro characterization of poly(ethylene glycol)-albumin hydrogel
      microparticles.
AB  - High water content hydrogel microparticles based on the cross-linking of albumin
      with activated poly(ethylene glycol) were synthesized. The influence of different
      synthesis parameters on the physicochemical characteristics of the
      microparticles, such as the type of oil and of albumin, and the molecular weight
      of PEG, was evaluated. The water content of the microparticles ranged from 95 to
      98%, increasing with an increase of the molecular weight of PEG. At optimal
      conditions, microparticles with sizes ranging from 3 to 50 MUm were prepared.
      These microparticles showed a negatively charged surface. They were freely
      dispersed in PBS buffer and they were stable at 4 degrees C for times varying
      from 0.5 to 10 months. Initial stirring speed and molecular weight of PEG were
      the 2 main factors that significantly affected microparticle size. High
      hydrophilicity, good stability and modulable size make this hydrogel an
      attractive matrix for protein or cell immobilization for biomedical applications.

PMID- 21859519
TI  - Cytocompatible performance of thermosensitive poly(N-isopropylacrylamide)
      nanoparticles.
AB  - The development of biomedical materials with biocompatibility, especially
      cytocompatibility, is the frontal research field for material science, biology,
      medicine, pharmacology and related interdisciplines. We have successfully
      synthesized a new biomedical material, PNIPAM-g-P(NIPAMco-St) (PNNS) core-shell
      nanoparticles, and investigated its thermosensitive and fluorescent properties.
      In order to evaluate the cytocompatibility of the PNNS nanoparticles, the effect
      of the PNNS nanoparticles on the human ether-ago-go-related gene (hERG) K(+)
      channel in HEK-293 cells was investigated for the first time with the inverted
      fluorescence microscope and the whole-cell patch-clamp technique. The PNNS
      nanoparticles can be adsorbed on the surface of the cell membrane of HEK-293
      cells, and cannot change the structure of HEK-293 cells. The low concentration of
      the PNNS nanoparticles can slightly inhibit the stable and tail current of the
      hERG K(+) channel, left-shift the activation curve of the hERG K(+) channel and
      decrease the deactivation time constant (tau)of the hERG K(+) channel. However,
      in the presence of the high concentration of the PNNS nanoparticles, the changes
      mentioned above gradually return to the level in the absence of the PNNS
      nanoparticles. These results indicated that the PNNS nanoparticles can not damage
      the cells. Thus, the PNNS nanoparticles have a good cytocompatibility and might
      be applied as a biomedical material. 

PMID- 21859521
TI  - Letter - Response to 'How to protect general practice from child protection'
AB  - The bad news is that the BJGP published under such a negative and provocative
      title without balanced debate, in contrast to the recent BMJ head-to-head debate
      'Has child protection become a form of madness'.1,2 One interesting comparison
      made in that debate is that Sweden and Finland spend 50% more of their gross
      domestic product on children and families than we do in the UK, we spend 200%
      more than they do on social problems. In my view these figures help us understand
      societal attitudes that have knock-on effects through all services for children
      and families including general practice. The current UK GP contract is certainly
      not child and family friendly and it is unlikely that current NHS changes will
      improve matters.Mike Fitzpatrick's latest letter over-emphasises the personal
      while flagging up the real difficulties for general practice.3 My work as a
      frontline GP and my statutory role as a named doctor for safeguarding children
      allows me to understand these difficulties, and indeed the importance of making
      vulnerable adults safe that he highlights in the same Journal.4The good news is
      that the great majority of children grow up well and happy in their families and
      GP practices support them in this. I emphasise this when delivering safeguarding
      training to GPs. In doing this work GPs can develop a sense of why something is
      going wrong. With appropriate use of their knowledge, skills, and information,
      GPs can address the needs of children and their families across the spectrum of
      vulnerability and need through to abuse and neglect. There is no question that
      this is challenging, but in the UK all professionals are obliged by statute to
      fulfil our professional roles and responsibilities. Those specific to general
      practice are on pages 60-63 of Working Together to Safeguard Children 2012.5GP
      colleagues in Cornwall show appreciation of the importance of safeguarding, but
      many feel there is too much guidance and insufficient resources. The majority of
      the practices value the RCGP/NSPCC Toolkit for Safeguarding Adults and Young
      People, that being written for GPs by GPs helps practices establish policies and
      procedures on safeguarding which work.6 I commend the RCGP for grasping the
      safeguarding nettle, collaborating with the NSPCC to produce this toolkit, and
      including safeguarding as one of the ten priorities of the RCGP Child Health
      Strategy for 2012-15.7 Can the BJGP help the College bring this strategy forward?
      Up to 25% of our patients are children. They are the future of the UK.

PMID- 21859520
TI  - Synergistic effect of biochemical factors and strain on the smooth muscle cell
      differentiation of adipose-derived stem cells on an elastic nanofibrous scaffold.
AB  - Adipose-derived stem cells (ASCs) have been the subject of many tissue
      engineering studies, mainly because of their multipotential properties. We have
      focused on the potential of human ASCs (hASCs) for smooth muscle cell (SMC)
      differentiation in cardiovascular tissue engineering. In this study, we
      investigated the combined effect of differentiation factors along with strain
      utilizing a customized device on hASCs proliferation and consequent
      differentiation into SMCs on an elastic nanofibrous scaffold. The cell
      proliferation increased in strain-stimulated culture and was more affected by
      media composition as compared to in static culture. Differentiation factors did
      not have an influence on SM alpha-actin (alpha-SMA) and myosin heavy chain (MHC)
      expression in static culture. However, alpha-SMA and MHC expression were affected
      by differentiation factors in strain culture, in particular, showing that
      treatment with retinoic acid significantly increased the expression of alpha-SMA
      (3.6-fold) and MHC (2-fold) as compared to strain alone. This study demonstrated
      the synergic effect of strain and biochemical factor on the SMC differentiation
      of hASCs and provided a useful method for the application of stem cells in
      mechano-active tissue engineering. 

PMID- 21859522
TI  - Let us take blood.

PMID- 21859523
TI  - Letter - Response to 'Is patient-centred care a tautology?'
AB  - There are often many interpretations of patient-centred care. The plethora of
      information at a patients disposal coupled with current financial strictures,
      highlights the importance of the concept of patient-centred care and its place in
      providing evidence based medicine that is cost-effective.Many PCTs and hospitals
      have and continue to place increasing restrictions in various aspects of health
      care; screening tests, for example, cervical smear, pathological and radiological
      investigations, not to mention the proliferation of referral management schemes.
      All these are directed, it seems, towards improving care, containing costs, and
      hopefully enriching the patient experience. Whether these various attributes are
      ever reconcilable is a matter of dispute and interest. However, it would seem
      prudent to consider patient-centred care as a consideration of a patient's
      likes/dislikes and views in the light of the available facilities. This places
      upon the doctors the need to describe and discuss the restrictions in place, and
      the options available within those restrictions, with as full a disclosure of
      relevant information as possible. This would then enable the patient to make an
      informed choice. The doctor serves as the source of information and the director
      in encouraging, without coercion, the patient towards the most appropriate
      choice.Too often patient-centred care is also confused with the exercise of
      autonomy by the patient. Respect for autonomy is often taken to mean acceding to
      the request of a patient. On the contrary, autonomy is best viewed as an
      expression of choice by an informed patient. Choice in this case would be one
      from the available options at the time, currently this would entail a discussion
      of cost and clinical effectiveness within the parameters of availability.Now, one
      could argue that this is whatdoctors should always have been doing. One benefit
      of the current restrictions is to return doctors to their professional roots and
      to encourage evaluation of the scope of care with patients.In both these
      scenarios doctors would be required to address the perennial issue of needs
      versus wants and their own professionalism.

PMID- 21859524
TI  - Medical professionalism and pay-for-performance.

PMID- 21859525
TI  - Letter - Response to 'Future-proofing primary health care: GP recruitment and
      retention in the new NHS'
AB  - I am increasingly bemused by the narrowing and blinkered view of training to
      becoming a GP. Rosenthal and Chana1 comment 'many trainees still spend part of
      this time in posts that offer traditional hospital-based experience that may not
      reflect the context of new community based service models'. Cautiously I would
      like to add the comment 'so what?' We do want 'well rounded' GPs, people open to
      new ideas, and who are open to 'lifelong learning.' Many who qualified at a
      similar time to me will have done hospital jobs as 'part of the team.' Six months
      at the end of which we were hopefully competent but also confident. Confident.
      Now that's a word we haven't been using too much recently but, as long as not
      false, important.Doing 6 months and making a good job of a delivery or episiotomy
      repair, doing pleural taps or biopsies, covering the paediatric clinic when the
      consultant had to rush off. Not perhaps relevant to my job now but it did instill
      a confidence and satisfaction to my work. There is now much less 'hands
      on'.Interestingly a local gastroenterologist recently told me he used to teach
      his GP trainees to do endoscopies, no longer, as 4 months is 'not enough.' We now
      have tasters that might encourage some degree of competence ('please sign me up'
      ) but are we creating doctors with no confidence in their own abilities?I like
      the idea of First5, encouraging doctors as they start their careers as GPs,
      dealing with issues, and educating around the GP mantle. It is a long career and
      may become longer so we need to generically give new GPs the tools to handle the
      future. Are we narrowing so much and trying too hard with training that we're
      taking the enjoyment out of the process, when perhaps some of this could be done
      later? It is now rare to have colleagues, who had done several years as
      gynaecologists/surgeons, join our ranks and I think we have lost something
      here.In my GP career I have been very grateful for sabbaticals to try working in
      different places/environments. This also seems to becoming more difficult and not
      encouraged generally while trying to achieve CCT. That great idea of learner-led
      education, particularly for trainees, seems to have gone out of the window.I
      suppose I am saying, can we be a bit more generic in our training years, widen
      our horizons again, and use First5 to help settle doctors into the rewarding job
      we do?

PMID- 21859528
TI  - United States environmental protection agency perchlorate method 332.0.
      Statistically sound recovery studies in simulated drinking water.
AB  - This research is a continuation of an earlier work, which evaluated the United
      States Environmental Protection Agency's Perchlorate Method 332.0, in which
      standards were prepared in deionized water over an extended concentration range
      (i.e., to a maximum of 200 MUg/L). This current paper investigates the
      performance of the same method in which standards were made in simulated drinking
      water. A microbore format with a 15-MUL injection volume was employed to conduct
      a recovery study and generate recovery curves (which hold the key to a
      statistically sound assessment of method performance in more complex matrices).
      The maximum analyte concentration range was 1 to 200 MUg/L. For various subset
      concentration ranges, recovery evaluations were made using both raw peak-area
      data and analyte responses scaled by the internal standard (ISTD). The results
      indicate that in complicated matrices such as drinking water, ISTDs may not
      provide simultaneously high precision and recovery.

PMID- 21859529
TI  - Elucidating the redox cycle of environmental phosphorus using ion chromatography.
AB  - Historically, it was assumed that reactive, inorganic phosphorus present in
      pristine environments was solely in the form of orthophosphate. However, this
      assumption contradicts theories of biogenesis and the observed metabolic behavior
      of select microorganisms. This paper discusses the role of ion chromatography
      (IC) in elucidating the oxidation-reduction cycle of environmental phosphorus.
      These methods employ suppressed-IC, coupled with tandem conductivity and
      electrospray mass spectrometry detectors to identify and quantify phosphorus
      oxyanions in natural water, synthetic cosmochemical, and biological samples.
      These techniques have been used to detect phosphite and orthophosphate in
      geothermal hot springs. Hypophosphite, phosphite, and orthophosphate have been
      detected in synthetic schreibersite corrosion samples, and termite extract
      supernatant. Synthetic schreibersite corrosion samples were also analyzed for two
      poly-phosphorus compounds, hypophosphate and pyrophosphate, and results show
      these samples did not contain concentrations above the 1.3 and 2.0 MUM respective
      3sigma limit of detection. These methods are readily adaptable to a variety of
      matrices, and contribute to the elucidation of the oxidation-reduction cycle of
      phosphorus oxyanions in the environment. In contrast to most studies, these
      techniques have been used to show that phosphorus actively participates in redox
      processes in both the biological and geological world.

PMID- 21859530
TI  - Ion chromatography detection of fluoride in calcium carbonate.
AB  - Fluoride in aquatic systems is increasing due to anthropogenic pollution, but
      little is known about how this fluoride affects organisms that live in and around
      aquatic habitats. Fluoride can bioaccumulate in structures comprised of calcium
      carbonate, such as shells and skeletons of both freshwater and saltwater species
      as diverse as snails, corals, and coccolithophorid algae. In this article, ion
      chromatography (IC) techniques are developed to detect and quantify fluoride in a
      matrix of calcium carbonate. Solid samples are dissolved in hydrochloric acid,
      pretreated to remove the majority of the chloride ions, and then analyzed using
      IC. With these methods, the 3sigma limit of detection is 0.2 mg of fluoride/kg of
      calcium carbonate.

PMID- 21859531
TI  - Separation of -amino acids using a series of zwitterionic sulfobetaine
      exchangers.
AB  - A set of five new covalently bond sulfobetaine exchangers with inner quaternary
      amines and outer sulfonic acids have been prepared by attachment of a series of
      zwitterionic precursors to hyperporous divinylbenzene polymers using a grafting
      reaction. The series of zwitterionic exchangers have the same backbone and
      identical spacers to the polymeric backbone, as well as comparable capacities.
      The only difference is the chain length for one to five methylene groups between
      the charged functional groups. Chromatographic properties are examined by
      separation of alpha-amino acids using sodium acetate and nitric acid eluents. The
      separation mechanism is explored by varying eluent ionic strength and eluent pH,
      resulting in the conclusion that amino acids are separated due to cation exchange
      interactions. This is a behavior never before observed using zwitterionic
      exchangers. It contradicts the fact that sulfobetaine-type materials used in
      zwitterionic ion chromatography (ZIC) usually are well suited for anion
      separation and only poorly for cation separation. Contrary to anion separations
      using the identical set of exchangers, the materials with three and four
      methylene groups between the charges give the highest retention factors.
      Materials showing the high potential in ZIC separations of inorganic anions give
      low retention factors for amino acids and vice versa.

PMID- 21859532
TI  - Analysis of inorganic nitrogen and related anions in high salinity water using
      ion chromatography with tandem UV and conductivity detectors.
AB  - Over 97% of the Earth's water is high salinity water in the form of gulfs,
      oceans, and salt lakes. There is an increasing concern for the quality of water
      in bays, gulfs, oceans, and other natural waters. These waters are affected by
      many different sources of contamination. The sources are, but not limited to,
      groundwater run-off of nitrogen containing fertilizer, pesticides, cleaning
      agents, solid wastes, industrial waters, and many more. The final destinations of
      these contaminants are rivers, lakes, and bayous that eventually will lead to
      bays, gulfs, and oceans. Many industries depend on the quality of these waters,
      such as the fishing industry. In addition to wild marine life, there are large
      aquariums and fish and shrimp farms that are required to know the quality of the
      water. However, the ability of these industries to monitor their processes is
      limited. Most analytical methods do not apply to the analysis of high salinity
      waters. They are dependent on wet chemistry techniques, spectrophotometers, and
      flow analyzers. These methods do not have the accuracy, precision, and
      sensitivity when compared to ion chromatography (IC). Since the inception of IC,
      it has become a standard practice for determining the content of many different
      water samples. Many IC methods are limited in the range of analytes that can be
      detected, as well as the numerous sample sources of which the methods are
      applicable. The main focus of current IC methods does not include high salinity
      waters. This research demonstrates an ion chromatographic method that has the
      ability to determine low level concentrations of inorganic nitrogen and related
      anions (nitrite-N, nitrate-N, phosphorous-P, sulfate, bromide, chloride, sulfide,
      fluoride, ammonia, calcium, and magnesium) in a single run using a combination of
      UV and conductivity detectors. This method is applicable to various waters, and
      uses both freshwater and high salinity water samples.

PMID- 21859533
TI  - Determination of perfluorooctanoate and perfluorooctanesulfonate in water
      matrices by inline matrix elimination liquid chromatography with reversed phase
      separation and suppressed conductivity detection.
AB  - This work describes a new method for the determination of perfluorooctanoate
      (PFOA) and perfluorooctane sulfonate (PFOS) in water matrices by suppressed
      conductivity detection. Separation was achieved by isocratic elution on a
      reversed-phase column thermostated at 45 degrees C using an aqueous mobile phase
      containing boric acid and acetonitrile. The PFOA and PFOS content in the water
      matrix were quantified by a pre-concentration technique. For the concentration
      range of 1 to 15 ng/mL and 2 to 30 ng/mL, the linear calibration curve for PFOA
      and PFOS yielded coefficients of determination (R(2)) of 0.9995 and 0.9985,
      respectively. The relative standard deviations were smaller than 1.5% for PFOA
      and PFOS. The retention-time precision of four consecutive 12 h injections was
      smaller than 0.641% and 0.818%, respectively. The presence of common divalent
      cations, such as calcium, magnesium, and iron in water matrices impairs PFOS
      recovery. This drawback was overcome by applying inline matrix elimination
      method. The optimized method was successfully applied for drinking water, ground
      water, and seawater samples.

PMID- 21859534
TI  - Statistically sound calibration curves for chromatographic methods involving
      negative response data.
AB  - A statistical procedure is presented for calibrating chromatographic methods that
      generate negative chromatographic peaks. The technique is illustrated via data
      collected during the ion-chromatographic analysis of the ammonium ion in
      methansulfonic-acid solutions. A peak-integration protocol is explained and
      subsequent regression data are presented. For the concentration range of 1 to 5
      ppb, a quadratic model could be fitted to the calibration data, using ordinary
      least squares as the fitting technique. The precision was approximately +/- 0.5
      ppb, at 95% confidence.

PMID- 21859535
TI  - Preparation of polyaniline modified electrode in novel ionic liquid and its
      application in ion chromatography.
AB  - In this work, a promising electrochemical detector has been fabricated by
      immersing a glass carbon electrode (GCE) in aniline containing novel ionic liquid
      and scanning between -1.0 and 1.0 V for 40 cycles, and was used in ion
      chromatography (IC) system. The morphology of the modified electrode surface was
      characterized by scanning electron microscope (SEM). The polyaniline (PANI) film
      showed excellent electrocatalytic activity than bare GCE and provided enhanced
      selectivity and stability for the detection of ascorbic acid (AA). Separated by
      IC with phosphate buffer solution (pH = 5.2) as eluent, AA could be determined by
      the PANI/GCE successfully at the working potential of 0.3 V. The retention time
      of AA was approximately 5.75 min, and the peak shape of AA was satisfactory. The
      calibration curve of AA was linear (r > 0.99), in the range between 0.05 mg/L and
      1000 mg/L and the detection limit was 23.41 MUg/L (S/N = 3). The proposed method
      was successfully applied in the detection of AA in four beverage samples. The
      recoveries of AA in these samples were from 92.32% to 110.57%.

PMID- 21859536
TI  - Determination of inorganic anions in ethyl acetate by ion chromatography with an
      electromembrane extraction method.
AB  - In this work, the determination of inorganic anions in slightly water-soluble
      organic solvents (ethyl acetate) was realized by ion chromatography (IC) with a
      novel-efficient electromembrane extraction method. From an 8 mL ethyl acetate
      sample, three inorganic anions migrated through the pores of a polypropylene
      hollow fiber membrane, and into deionized water inside the lumen of the hollow
      fiber by the application of 600 V. The transport was forced by an electrical
      potential difference sustained over the liquid membrane, resulting in
      electrokinetic migration of inorganic anions from the donor compartment to the
      acceptor solution. After the electromembrane extraction, the acceptor solution
      was analyzed by IC with a sodium carbonate-sodium bicarbonate eluent. The applied
      voltage, stirring speed, and extraction time for controlling the extraction
      efficiency were optimized. Within 10 min of operation at 600 V, chloride,
      bromide, and sulfate were extracted with recoveries in the range 76-110%, which
      corresponded to a linear range of 0.01-1 mg/L. The procedure was applied to the
      analysis of inorganic anions in a real ethyl acetate sample and expands onto
      other slightly water-soluble organic solvents.

PMID- 21859537
TI  - Simultaneous determination of organic and cationic species in explosives residues
      with column-switching liquid chromatography-ion chromatography system.
AB  - A new column-switching method has been proposed for the determination of 14
      organic explosives (1,3,5,7-tetranitro-N-methylaniline, 1,3,5-trinitro-1,3,5
      triazacyclohexane, 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, nitrobenzene, 2,4,6
      N-tetranitro-N-methylaniline, Trinitrotoluene, 4-amino-2,6-dinitrotoluene, 2
      amino-4,6-dinitrotoluene, 2,6-dinitrotoluene, 2,4-dinitrotoluene, 2-nitrotoluene,
      4-nitrotoluene, and 3-nitrotoluene) and/or five inorganic cations (Na(+),
      NH(4)(+), K(+), Mg(2+), and Ca(2+)) using liquid chromatography linked to ion
      chromatography by a switching valve. The mobile phase was methanol-water (40/60,
      v/v) for a C18 reversed-phase column and 3 mM of methanesulfonic acid (pH 2.5)
      for a cation-exchange column, respectively. Under the optimal conditions, the 14
      organic explosives and the five inorganic cations were separated and detected
      simultaneously within 45 min. The limits of detection (S/N = 3) of the 14 organic
      explosives and the five inorganic cations were in the range of 0.0048-0.0333 mg/L
      and 0.0116-0.1851 mg/L, respectively. The linear correlation coefficients were
      0.9971-0.9999, and the relative standard deviation of the retention time and the
      peak area were 0.02-0.31% and 0.51-3.64%, respectively. The method was
      successfully applied to the determination of organic explosives and inorganic
      cations in dust samples.

PMID- 21859538
TI  - Simultaneous determination of arsenite and arsenate in arsenic trioxide injection
      by dual detection ion chromatography.
AB  - This paper describes a rapid method to determine arsenite assay and arsenate
      impurity in Arsenic Trioxide Injection using a single conductivity detector. The
      arsenite assay was determined in a non-suppressed conductivity detection mode and
      arsenate impurity was quantified in a suppressed conductivity detection mode.
      Dual-conductivity detections were enabled by valve switching and time
      programming. The method was validated with respect to specificity, linearity,
      precision, accuracy, stability, and limit of quantification. The limit of
      detection and quantification for arsenite were 0.855 mg/L and 2.593 mg/L, and
      0.044 mg/L and 0.133 mg/L for arsenate, respectively.

PMID- 21859539
TI  - Development and validation of stability indicating method for the determination
      of exemestane by reverse phase high performance liquid chromatography.
AB  - Exemestane is an aromatase inhibitor used in the treatment of breast cancer. A
      selective stability-indicating reversed-phase high performance liquid
      chromatography (RP-HPLC) method has been developed which can separate and
      accurately quantitate low levels of exemestane. The stability-indicating
      capability of the method was demonstrated by adequate separation of exemestane
      and all the degradation product peaks from exemestane peak and also from each
      other in stability samples of exemestane. Chromatographic separation of
      exemestane and its degraded products were achieved by using isocratic elution at
      a flow rate of 1.0 mL/min on a C18 reverse phase column (Phenomenex, size: 250 *
      4.60 mm, particle size 5 MUm) at ambient temperature. The mobile phase used for
      the analysis was acetonitrile-water (60:40, %v/v) with UV visible detection at
      242 nm. The proposed method was used to study the degradation behavior of drug
      under various stress conditions as per ICH recommended guidelines.

PMID- 21859540
TI  - Simultaneous determination of 16 sulfonamides in animal feeds by UHPLC-MS-MS.
AB  - A fast and sensitive method was developed for the simutaneous quantitative
      determination of 16 sulfonamides in animal feeds using ultra-high performance
      liquid chromatography tandem mass spectrometry (UHPLC-MS-MS). With the developed
      method, a feed sample can be analyzed in less than 2 h. A solid phase extraction
      method using acetonitrile and basic alumina column was developed to extract and
      purify sulfonamides from animal feeds. The analysis time can be greatly reduced
      with this method compared with previous reports. A linear range of 0.2
      approximately 40 ng/mL (R(2) > 0.996) were obtianed for most of the compounds.
      The limits of quantification for all sulfonamides were in the range of 0.5
      approximately 20 MUg/kg. The high precision and accuracy of this method were
      represented by average recoveries ranging from 80% to 120% and coefficients of
      variation of less than 10% for spiked animal feed samples. The method is suitable
      for fast determination of sulfonamides in concentrates, premixes, and complete
      feeds.

PMID- 21859541
TI  - Determination of some phenolic compounds in red wine by RP-HPLC: method
      development and validation.
AB  - A methodology employing reversed-phase high-performance liquid chromatography (RP
      HPLC) was developed and validated for simultaneous determination of five phenolic
      compounds in red wine. The chromatographic separation was carried out in a C(18)
      column with water acidify with acetic acid (pH 2.6) (solvent A) and 20% solvent A
      and 80% acetonitrile (solvent B) as the mobile phase. The validation parameters
      included: selectivity, linearity, range, limits of detection and quantitation,
      precision and accuracy, using an internal standard. All calibration curves were
      linear (R(2) > 0.999) within the range, and good precision (RSD < 2.6%) and
      recovery (80-120%) was obtained for all compounds. This method was applied to
      quantify phenolics in red wine samples from Santa Catarina State, Brazil, and
      good separation peaks for phenolic compounds in these wines were observed.

PMID- 21859542
TI  - Identification and interaction of amino acids with leucine-anthracene reagent by
      TLC and spectrophotometry: experimental and theoretical studies.
AB  - A new reagent has been synthesized by coupling anthracene moiety to L-leucine.
      The reagent is characterized by different analytical techniques. It is capable
      for easy identification of various amino acids on thin-layer chromatography
      plates by developing distinguishable colors (detection limit between 0.1-0.5 MUg
      at cold condition and 0.1-0.4 MUg after heating). This reagent also binds with
      different amino acids very strongly in solution (methanol). Estimation of
      equilibrium binding constants of this new reagent with different amino acids has
      also been carried out. The values of the binding constants are lowest for L
      Tyrosine (6.86 * 103 dm3 mol(-1)) and highest for L-Arginine monohydrochloride
      (8.86 * 105 dm3 mol(-1)) at 25 degrees C. A theoretical study (Hartree-Fock) has
      been performed to investigate the interaction of the reagent with a
      representative amino acid, glycine.

PMID- 21859543
TI  - [Modified Restriction Enzyme-based Detection of EGFR Mutations in Lung Cancer].
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation in lung cancer
      is a reliable predictor of the efficacy of tyrosine kinase inhibitors, so
      detection of gene mutation has very important clinical significance. The aim of
      this study is to optimize conditions for restriction enzyme-based mutant enriched
      detection of EGFR mutation in lung cancer specimens. METHODS: EGFR somatic
      mutations identified in DNA specimens from 251 lung adenocarcinomas with modified
      mutant enriched method and direct sequencing were compared. The sensitivity of
      the modified method was determined by serial dilution of mutant-carrying lung
      cancer cells in wild-type cells. RESULTS: 46 deletion mutations in exon 19 and 26
      point mutations in exon 21 were found by sequencing, while modified method
      identified another 78 deletions in exon 19 and 57 substitutions in exon 21 with a
      mutation rate of 53.8%. Sensitivity of this modified method was 0.5% (mutant/wild
      type) in serial diluted cells. CONCLUSIONS: The modified restriction enzyme-based
      method is convenient for clinical EGFR mutation screening in non-small cell lung
      cancer for its simpleness, cost-saving and high sensitivity.

PMID- 21859544
TI  - [Effect of rs2293347 Polymorphism in EGFR on the Clinical Efficacy of Gefitinib
      ?in Patients with Non-small Cell Lung Cancer].
AB  - BACKGROUND: Genetic variations of the epidermal growth factor receptor (EGFR) may
      alter the protein function and therapeutic efficacy of EGFR inhibitors. The aim
      of this study is to investigate the association between single nucleotide
      polymorphism rs2293347 in EGFR and the clinical outcome in patients with advanced
      non-small cell lung cancer (NSCLC) treated with gefitinib. METHODS: A total of 88
      advanced NSCLC patients treated with gefitinib were analyzed in the present
      study. Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method was conducted to analyze the genotype. The association study was
      performed between genotypes and clinical efficacy among 88 patients. RESULTS:
      rs2293347 was associated with the efficacy of gefitinib. The response rate for
      the rs2293347 GG was significantly higher than that for the GA or AA (71.4% vs
      36.0%, P=0.002). rs2293347 GG genotype was also associated with longer
      progression-free survival compared with GA or AA genotype (10 months vs 3 months,
      P=0.005). No significant difference was shown on the overall survival (OS)
      (P=0.409). CONCLUSIONS: rs2293347 polymorphism in exon 25 is associated with the
      clinical efficacy of gefitinib and may be a potential biomarker to predict the
      clinical outcome in advanced NSCLC patients treated with gefitinib.

PMID- 21859545
TI  - [Neuroendocrine differentiation is not a malignant index of non-small cell lung
      cancer].
AB  - BACKGROUND: A debate has been ongoing whether non-small cell lung cancer(NSCLC)
      with neuroendocrine(NE) differentiation likely indicates malignant behavior, poor
      prognosis, and sensitivity to chemotherapy. In response to this issue, we
      retrospectively investigated NE differentiation in NSCLC patients who underwent
      anatomical pulmonary surgery. METHODS: A total of 274 patients who met the
      inclusion criteria through January 2000 to December 2008 were enrolled in this
      study because they had the detailed material and enough paraffin tumor samples
      for tissue microarray. The recommended antibody panel consisted of CgA, Syn,
      NCAM, Leu-7, PGP9.5, and MAP-2. We also counted Ki-67 in the tissues to present
      the nuclear proliferation index. The Kaplan-Meier estimator and the Cox
      proportional hazard model multivariate analysis were applied to observe the
      relationship between NE differentiation and postoperative survival of the
      patients. RESULTS: The Cox analysis of different NE score combinations on the
      prognosis of NSCLC after surgical treatment did not reach statistical
      significance (score 1, score 2, and score>=3 vs score 0, P=0.527; score 0 vs
      score >=1, P=0.791; score<2 vs score>=2, P=0.163; score<3 vs score>=3, P=0.293).
      The Kaplan-Meier estimator did not give significant difference in the survival of
      NE score combinations in each pTNM layer. In the perioperative chemotherapy
      group, we also did not find a positive correlation for the survival analysis of
      NE score combinations (score 1, score 2, and score>=3 vs score 0, P=0.692; score
      0 vs score>=1, P=0.922; score<2 vs score >=2, P=0.264; score<3 vs score>=3,
      P=0.484). CONCLUSIONS: The NE differentiation of NSCLC reflects some structure
      and functional characteristics of NELT, although it cannot be used as an
      independent factor of biological behavior and survival for NSCLC patients who
      underwent surgery in our group.

PMID- 21859546
TI  - [Clinical analysis of interventional bronchoscopy for the treatment of malignant
      obstructive atelectasis].
AB  - BACKGROUND: Obstructive atelectasis is frequently accompanied by pulmonary
      infection and hypoxia. The key to treating this condition is by directly
      reopening the obstructive airway. The aim of the present study is to explore the
      safety and efficacy of interventional bronchoscopy for the treatment of malignant
      obstructive atelectasis. METHODS: A total of 120 cases with pathology-proved
      malignant obstructive atelectasis were retrospectively analyzed for the treatment
      of argon plasma coagulation and cryosurgery under bronchoscopy. Patients' age is
      between 5 and 90 years old. RESULTS: A total of 120 cases had 187 atelectasis
      originating from 98 lesions with primary airway tumors and 89 with metastases.
      The most common location of atelectasis was in the upper lobe in the primary
      group and in the single lung in the metastasis group. Although there was no
      significant difference in tumor debulging between the two groups, the reopening
      rate of atelectasis was lower in the primary group than that in the metastasis
      group. The Karnofsky physical score significantly increased, and shortbreath
      scale decreased after interventional bronchoscopy. Among the patients, 3/4 had
      hypoxemia and 3.4% had severe bleeding, which caused the death of 1 patient
      during a procedure. The mean survival time was 6 months, and the survival rate of
      1 year was 27.1%. CONCLUSIONS: Bronchoscopy can rapidly and effectively debulge
      the airway tumor and reopen the atelectasis.

PMID- 21859547
TI  - [CYP1A1 gene and GSTM1 gene polymorphism and the combined effects and risk of
      lung cancer: a meta-analysis].
AB  - BACKGROUND: Cytochrome P450A1 (CYP1A1) gene and glutathione S-transferase M1
      (GSTM1) gene both have single nucleotide polymorphisms and effects on lung
      cancer. Currently, however, the risk of lung cancer due to the CYP1A1 and GSTM1
      genes has no clear evidence. In this present study, we propose to research the
      combined effects of CYP1A1 gene and GSTM1 gene polymorphism and their risks to
      lung cancer. METHODS: We conducted the study at different research areas and
      using various database, including PubMed, Embase, China Biology Medicine (CBM)
      and China National Knowledge Infrastructure (CNKI) last March 31, 2011. We
      calculated the adjusted odds ratio (OR) and 95% confidence interval (CI) for lung
      cancer in each study. Using STATA 10, a statistical program, we summarized the
      calculated estimates for the adjusted ORs and performed a meta-analysis. RESULTS:
      The meta-analysis includes 15 research studies. The CYP1A1 IIe/Val genotype which
      carries a homozygous mutant type has a higher chance of risk to lung cancer than
      that which carries a homozygous mutant type and a heterozygous type when the
      GSTM1 carries a null genotype. As a result, OR was 3.18 (95%CI: 1.27-7.98), 1.45
      (95%CI: 1.08-1.94), respectively. Meanwhile, the same conclusion was obtained for
      the CYP1A1 MspI genotype. The overall OR was 1.90 (95%CI: 1.00-3.58), 1.57
      (95%CI: 1.23-2.00), respectively. CONCLUSIONS: We discovered through our meta
      analysis that the combined effects of CYP1A1 gene and GSTM1 gene polymorphism are
      significantly associated with an increased risk to lung cancer. We also found
      that homozygous mutant genotype of CYP1A1 has a higher chance of risk to lung
      cancer than the homozygous or heterozygous genotype.

PMID- 21859548
TI  - [Circulating lymphocyte subsets in patients with lung cancer and their prognostic
      value].
AB  - BACKGROUND: Lung cancer is one of the most common malignancies. The aim of this
      study is to investigate the relationship between the change of lymphocyte subsets
      in the peripheral blood of lung cancer patients and the survival rate. METHODS:
      Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+,
      CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells) in peripheral blood
      obtained from 221 patients with primary lung cancer without any treatment and
      from 96 healthy blood donors as the control group. The result was combined with
      clinical and follow-up data and statistical analysis was conducted. RESULTS: The
      levels of CD3+ and CD8+ in the patient group are significantly lower compared
      with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and
      NK cells are significantly higher (P<0.05). CD8+ is significantly higher in the
      small cell lung cancer (SCLC) group compared with the non-small cell lung cancer
      (NSCLC) group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05). There were
      no significant differences in different stages and differentiation (P>0.05) in
      the NSCLC group. The level of CD3+ was significantly higher compared with the pre
      chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the
      post-chemotherapy group (P<0.05). More survival opportunities will be obtained
      for patients with no increase in CD44+ after chemotherapy (P=0.021), but the
      other three indices have no obvious influence on survival. CONCLUSIONS:
      Widespread changes of lymphocyte occur in the peripheral blood of patients with
      lung cancer. There is a significant correlation between the change of CD44+ and
      the prognosis after chemotherapy.

PMID- 21859549
TI  - [Diagnosis and treatment for pulmonary sclerosing hemangioma].
AB  - BACKGROUND: The concept of pulmonary sclerosing hemangioma (PSH) was proposed
      only 50 years ago. PSH features several characteristics that should be
      differently diagnosed with lung cancer. The aim of this study is to
      retrospectively review the diagnosis and treatment of 48 cases of PSH, review
      recent publications about this topic, and address reasonable diagnosis and
      treatment methods. METHODS: Forty-eight patients with PSH were enrolled and
      consecutively treated from January 2001 to April 2011. Clinical presentations,
      image characteristics, pathologic morphologies, and prognostic data were
      analyzed. RESULTS: Twenty-seven PSH cases (56.3%) were asymptomatic. Tumor
      diameters ranged from 0.2 to 7.0 cm, with an average diameter of 2.1 cm, and
      involved both lobes of the lungs. Enlarged lymph nodes in the mediastinum were
      detected via computed tomography (CT) scans in 15 cases (31.3%). Only 47 patients
      underwent surgery. Pulmonary wedge resection was performed in 29 cases (61.7%)
      while lobectomy was performed in 14 (29.8%). The tumor was removed in 3 cases
      (6.4%) and anterior mediastinal tumor resection was performed in 1 case (2.1%).
      Forty-seven patients reported no recurrence during follow-up while one patient
      refused surgery after a CT-guided biopsy with no progression during the 28-month
      follow up period. CONCLUSIONS: The exact diagnosis of PSH is difficult prior to
      surgery. Surgery is an effective method of treatment that allows both definite
      diagnosis and accurate therapy. The prognosis of PSH is favorable.

PMID- 21859550
TI  - [Sealing of airway fistulas for metallic covered z-type stents].
AB  - BACKGROUND: Treating airway fistulas, including esophagorespiratory fistulas
      (ERFs), bronchopleural fistulas (BPFs), and tracheomediastinal fistulas (TMFs),
      is difficult. The aim of this study is to evaluate the safety and clinical
      efficacy of metallic covered Z-type stents (CZTS) for the treatment of airway
      fistulas through bronchoscopy or fluroscopy. METHODS: Thirty-eight patients with
      fistulas between the esophagus, mediastina, and airways (32 ERFs, 5 BPFs, and 1
      TMF) were retrospectively reviewed after treatment with covered metallic
      esophageal and airway stents. The fistulas were caused by esophageal (n=26),
      bronchogenic (n=11), and thyroid (n=1) carcinomas. RESULTS: Forty-six fistulas
      were found in 38 patients. The fistula size ranged from 0.5 cm to 7.0 cm. Forty
      airway covered metal stents (24 Y-type, 8 L-type, and 8 I-type) and 24 esophageal
      metal stents were placed. Complete responses to the sealing effects of fistulas
      were noted in 4.3% of all the fistulas, 60.9% showed complete clinical responses,
      23.9% showed partial responses, and 10.9% showed no response. An effectivity rate
      of 89.1% was observed, and the median survival duration of all patients was 5
      months. CONCLUSIONS: The use of CZTS appears to be safe and feasible for the
      palliative treatment of ERFs, BPFs, and TMFs. Airway stent placement is
      recommended for patients with ERF. In the event that airway stents fail,
      esophageal stents should be given. Airway bifurcation stents were observed to be
      especially suitable for the sealing of fistulas near the trachea carina.

PMID- 21859551
TI  - [Advances of LKB1-AMPK-mTOR Signaling Pathway in Tumor].

PMID- 21859552
TI  - [The study of PI3K/AKT pathway in lung cancer metastasis and drug resistance].
AB  - PI3K/AKT signal pathway is an important intracellular signal transduction
      pathway. It plays important roles in cell apoptosis and survival by affecting the
      activity of downstream effector molecules, and it is closely associated with the
      development and progression of human tumors. Recent researches of PI3K/AKT
      indicate that this pathway plays important roles in tumor cells proliferation,
      blood vessel neogenesis, tumor metastasis and resistance to chemotherapy and
      radiotherapy. The profound research of PI3K/AKT is beneficial to the prevention
      of tumor and to the finding of potential targets for new drugs. This article
      reviewed the composition, function and regulation of PI3K/AKT signal pathway, and
      its effect in metastasis and drug resistance of lung cancer.

PMID- 21859553
TI  - [The research progress about Wnt pathway of lung cancer stem cells].
AB  - Being the most critical signaling molecule in the Wnt pathway, the Wnt/beta
      catenin signaling pathway plays an important role in the maintenance of the cell
      proliferation and clone formation of lung cancer stem cells. Since it is closely
      related to the WNT pathway, the proliferation of lung cancer stem cells can be
      restrained by blocking the WNT pathway or influencing its key protein. Such
      method provides a new method for the treatment of lung cancer. By summarizing the
      state of-the-art research of lung cancer stem cells and the Wnt pathway from 2005
      to 2010, their relationship is investigated.

PMID- 21859554
TI  - Combination of lenalidomide and rituximab in elderly patients with relapsed or
      refractory diffuse large B-cell lymphoma: a phase 2 trial.
AB  - BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of
      aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up
      to half of all patients relapse. Here we report the results from a phase 2,
      single-arm, single-center trial evaluating the safety and efficacy of
      lenalidomide plus rituximab in elderly patients with relapsed or refractory
      DLBCL. PATIENTS AND METHODS: Between March and June 2009, elderly patients (65
      years of age or older) with relapsed/refractory DLBCL who had been heavily
      pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day
      cycle) was initiated for four cycles and rituximab (375 mg/m(2)) was administered
      on day 1 and day 21 of each 28-day cycle for four cycles. After this induction
      phase, patients achieving a complete response (CR), partial response (PR), or
      stable disease (SD) were given lenalidomide maintenance therapy at the same
      schedule for another 8 months. RESULTS: A total of 23 patients with a median of
      three prior treatments (range, 2 to 8) were included. The overall response rate
      (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR,
      1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of
      these patients achieved a CR. Adverse events were manageable and the most common
      included neutropenia and thrombocytopenia. CONCLUSION: Oral lenalidomide in
      combination with rituximab is active in elderly patients with relapsed/refractory
      DLBCL with a high percentage of patients achieving a continuous CR after
      lenalidomide maintenance.

PMID- 21859555
TI  - Essential thrombocythemia and multiple myeloma: two rare diseases in one patient.

PMID- 21859556
TI  - Association study of selected genetic polymorphisms and occurrence of venous
      thromboembolism in patients with multiple myeloma who were treated with
      thalidomide.
AB  - INTRODUCTION/BACKGROUND: Venous thromboembolism (VTE), with the subsequent risk
      of pulmonary embolism, is a common adverse effect of thalidomide treatment in
      patients with multiple myeloma (MM). In our retrospective study, we analyzed
      candidate single-nucleotide polymorphisms (SNP), CINP (rs7011), CETP (rs289747),
      ALDH1A1 (rs610529), CDKN1A (rs3829963), GAN (rs2608555), vascular endothelial
      growth factor (rs699947), and ALDH1A1 (rs168351), previously identified in a
      large association study based on the hypothesis-driven candidate gene approach
      nominated by the International Myeloma Foundation "Bank On A Cure" (3404 SNPs).
      In that study, the researchers built a classification tree that enables
      prediction of individual risk of VTE in patients with MM. PATIENTS AND METHODS:
      Genotypes of these SNPs were determined in an independent cohort of 111 patients
      with MM through TaqMan real-time polymerase chain reaction (PCR) allelic
      discrimination and were used for prediction of individual VTE risk. RESULTS: The
      results of this study did not confirm the ability of this classification tree to
      predict VTE risk in patients with MM from the Czech Republic; of these patients,
      21 (19%) developed high-grade VTE. However, in patients with VTE, we found higher
      frequency of the AC genotype in the CDKN1A gene (42.9% vs. 16.7%; odds ratio
      3.64) in comparison with the CC genotype (P = .015). SNPs of other genes as well
      as age and sex of the patients had no statistically significant influence on the
      risk of VTE. CONCLUSION: Further studies are needed to confirm the initial
      analysis that provided predictive information of genetic variations in patients
      with myeloma that may influence risk of VTE.

PMID- 21859558
TI  - The follow-up after radical surgery of colorectal cancer: is it time for a
      "tailored" strategy?
AB  - The problem of the surveillance for colorectal cancer after radical surgery is a
      widely debated argument. Like for other solid tumors, the issue is divided in 2
      main routes: the early diagnosis of recurrence and the early diagnosis of a
      second primary cancer. Genetic and molecular features have been recognized as
      useful tools to measure these risks, however, the instruments are still
      insufficient to design a personalized strategy for the patient. In an era of
      "tailored therapies" in oncology, even the follow-up of the surgically treated
      patient for colorectal cancer should enter "a tailor's shop in which several
      competent tailors" should be available to manage a complex problem.

PMID- 21859557
TI  - Prognostic and predictive markers in stage II colon cancer: is there a role for
      gene expression profiling?
AB  - Conventional clinical and pathologic risk factors in stage II colon cancer
      provide limited prognostic information and do not predict response to adjuvant 5
      fluorouracil-based chemotherapy. New prognostic and predictive biomarkers are
      needed to identify patients with highest recurrence risk who will receive the
      greatest absolute risk reduction from adjuvant chemotherapy. We review below the
      evidence for conventional risk factors in patients with node-negative colon
      cancer, followed by a discussion of promising new molecular and genetic markers
      in this malignancy. Gene expression profiling is an emerging tool with both
      prognostic and predictive potential in oncology. For patients with stage II colon
      cancer, the Oncotype DX Colon Cancer test is now commercially available as a
      prognostic marker, and the ColoPrint assay is expected to be released later this
      year. Current evidence for both of these assays is described below, concluding
      with a discussion of potential future directions for gene expression profiling in
      colon cancer risk stratification and treatment decision making.

PMID- 21859559
TI  - A phase I study of the chinese herbal medicine PHY906 as a modulator of
      irinotecan-based chemotherapy in patients with advanced colorectal cancer.
AB  - PHY906 is a novel Chinese herbal preparation that has been used in the Orient for
      over 1800 years to treat a wide range of gastrointestinal side effects including
      diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and
      clinical studies were conducted to further investigate the biologic and clinical
      activities of this herbal medicine. To ensure standardization and maintain
      interbatch reliability of PHY906, high performance liquid chromatography (HPLC)
      was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical
      studies using the murine Colon 39 tumor model showed that PHY906 protected
      against the weight loss associated with irinotecan treatment. In the presence of
      PHY906, mice were able to tolerate otherwise lethal doses of irinotecan.
      Significantly improved antitumor activity and overall survival were observed in
      animals treated with the combination of irinotecan and PHY906 versus irinotecan
      alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and
      leucovorin (LV) also resulted in at least additive antitumor activity with no
      increased host toxicity. Based on these in vivo studies, a phase I multicenter,
      double-blind, randomized, placebo-controlled, dose escalation, cross-over study
      of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV
      (IFL) in the first-line treatment of patients with advanced colorectal cancer
      (CRC) was conducted. The specific objectives of this clinical trial were to
      determine the safety and tolerability of PHY906 when administered concomitantly
      with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the
      pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38.

PMID- 21859560
TI  - Survival for metastatic colorectal cancer in the bevacizumab era: a population
      based analysis.
AB  - BACKGROUND: As of 2006, bevacizumab was available for the treatment of metastatic
      colorectal cancer (mCRC) in British Columbia (BC). This study compares survival
      between referred patients diagnosed with mCRC in 2003/2004 (pre-bevacizumab era)
      and 2006 (bevacizumab era). PATIENTS AND METHODS: The BC cancer agency (BCCA) is
      a cancer network treating approximately 60% of patients with mCRC in BC. For this
      study, all patients in the BCCA diagnosed with mCRC in 2003/2004 and 2006 were
      included. The primary objective was to compare overall survival (OS) between the
      2 cohorts. RESULTS: One thousand four hundred seventeen patients were included:
      969 from 2003/2004, and 448 from 2006. Between 2003/2004 and 2006, the proportion
      of patients treated with systemic therapy for mCRC increased (61.1% to 67.6%; P =
      .02). The only significant difference in treatment between the cohorts was in the
      proportion of patients who received bevacizumab (5.9% to 30.6%; P < .001). Median
      OS significantly differed between the 2 cohorts (13.8 to 17.3 months; P < .001).
      Median OS for patients who received systemic therapy increased (18.6-23.6 months;
      P = .001). Median OS for patients who did not receive systemic therapy was
      unchanged (6.1-5.9 months; P = .65). CONCLUSION: In this population-based study,
      median OS for mCRC significantly increased between 2003/2004 and 2006. An
      increase in the proportion of patients treated with systemic therapy, and the
      addition of bevacizumab to chemotherapy, seem to have contributed to this
      improvement in survival.

PMID- 21859561
TI  - Chemotherapy in rectal cancer: variation in utilization and development of an
      evidence-based benchmark rate of optimal chemotherapy utilization.
AB  - BACKGROUND: Published chemotherapy utilization rates for rectal cancer show
      considerable variation. Optimal chemotherapy utilization rates can serve as
      benchmarks to assess the quality of cancer care. The purpose of this study was to
      determine the optimal proportion of patients with rectal cancer who should
      receive chemotherapy at least once. PATIENTS AND METHODS: An optimal chemotherapy
      utilization tree was constructed using indications for chemotherapy identified
      from evidence-based treatment guidelines. Epidemiologic data were merged with
      treatment indications to calculate an optimal chemotherapy utilization rate; this
      rate was compared with reported actual rates of chemotherapy utilization.
      RESULTS: Chemotherapy is indicated at least once in 64% of patients with rectal
      cancer. Although the actual (Australian and United States data) and optimal
      utilization rates are comparable for patients presenting in stages II or III
      rectal cancer, actual utilization rates are higher than the optimal for stage I
      and lower than optimal for patients presenting in stage IV rectal cancer.
      CONCLUSION: Chemotherapy may be under-utilized in the initial management of
      patients presenting with metastatic rectal cancer.

PMID- 21859562
TI  - Appendiceal adenocarcinoids with peritoneal carcinomatosis treated with
      cytoreductive surgery and intraperitoneal chemotherapy: a retrospective study of
      in vitro drug sensitivity and survival.
AB  - PURPOSE: The purpose of this study was to present results on cytoreductive
      surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of
      appendiceal adenocarcinoid (AAC) with peritoneal carcinomatosis (PC), to assess
      drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report
      any discordant histopathology. METHODS: Ten patients were treated with CRS and
      HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data
      were recorded and matched with potential prognostic indicators. Drug sensitivity
      was assessed with short-term fluorometric microculture cytotoxicity assay and
      compared with peritoneal metastases from CRC. RESULTS: Patients with completeness
      of cytoreduction score (CC) <= 1 had better median survival (36.6 months) than
      those with CC > 1 (16.4 months). In the CC <= 1 group, 8 months elapsed between
      initial diagnosis and CRS with HIPEC compared with 22 months in the CC > 1 group.
      For standard drugs, tumor cells from AAC and CRC were equally sensitive; except
      for docetaxel, to which AAC was more sensitive than CRC. CONCLUSION: The CC-score
      correlated with overall survival. Candidates for this type of treatment should be
      referred early for evaluation in order to reach a better CC score. Drugs used for
      CRC also seem adequate for treatment of AAC, although other drugs, eg, docetaxel,
      might be more active.

PMID- 21859563
TI  - Assessing compliance with national comprehensive cancer network guidelines for
      elderly patients with stage III colon cancer: the Fox Chase Cancer Center
      Partners' initiative.
AB  - BACKGROUND: Fox Chase Cancer Center Partners (FCCCP) performs an annual quality
      review of affiliate practices based on National Comprehensive Cancer Network
      (NCCN) guidelines. Given recent treatment advances, we initiated this medical
      record review in elderly patients with stage III colon cancer to measure
      compliance with these guidelines. METHODS: Medical records of 124 patients age >=
      65 diagnosed with stage III colon cancer between 2003 and 2006 were reviewed.
      Metrics were developed and based on NCCN guidelines for workup and staging,
      treatment, and gerontology. Documentation was reviewed via paper (13 sites) and
      electronic record (2 sites). RESULTS: High compliance with staging and workup
      guidelines was noted with chest imaging (100%), stage (98%), computed tomography
      (CT) of the abdomen/pelvis (93%), pathology (91%), and carcinoembryonic antigen
      (CEA; 91%). Activities of daily living were documented commonly (83%) but
      colonoscopy less (75%). Age and life expectancy were discussed with the patient
      in only 49%. Nearly all patients (123 of 124 patients) received adjuvant
      chemotherapy, with 76 patients (61%) receiving oxaliplatin. Common regimens were
      FOLFOX (oxaliplatin plus infusional/bolus 5-fluorouracil and folinic acid) 54%, 5
      fluorouracil/leucovorin (5-FU/LV; 19%), and capecitabine (12%). Reasons for
      excluding oxaliplatin were comorbidity (68%), age (19%), and not specified (13%).
      Three-quarters of the patients had >= 12 lymph nodes sampled and 56% identified
      the radial margin. Nearly all patients (115 = 93%) received surveillance with
      history and physical and CEA. Surveillance CT was performed in 78% of the
      patients. CONCLUSIONS: A quality review of community oncology practices can
      assess implementation of treatment advances. Guideline compliance for elderly
      patients with stage III colon cancer is generally high. Forty percent did not
      receive oxaliplatin and documentation of life expectancy was infrequent. Further
      study of oncologist decision making for elderly colon cancer patients is
      warranted.

PMID- 21859564
TI  - A phase I/II study of capecitabine given on a week on/week off schedule combined
      with bevacizumab and oxaliplatin for patients with untreated advanced colorectal
      cancer.
AB  - BACKGROUND: A week on/week off capecitabine schedule with oxaliplatin/bevacizumab
      was evaluated in patients with metastatic colorectal cancer (mCRC). PATIENTS AND
      METHODS: Forty patients were required. The projected median progression-free
      survival (PFS) was 12 months (81% power, 1-sided level 0.1 log-rank test).
      Capecitabine dose was 2500 mg/m(2)/day on days 1-7 (n = 11) and was increased to
      3000 mg/m(2)/day (n = 29) in combination with oxaliplatin (85 mg/m(2)) and
      bevacizumab (5 mg/kg). Cycles were repeated every 2 weeks. RESULTS: Patient
      characteristics included Eastern Cooperative Oncology Group (ECOG) performance
      status 0 (n = 24) or 1 (n = 15); median age of 62 years (range, 38-81 years).
      Median cycles administered were 7 (range, 125), corresponding to 3.5 months'
      treatment duration. Pertinent grade 3/4 toxicities seen were diarrhea (18%), hand
      foot syndrome (10%), and peripheral neuropathy (10%). Bowel perforation in 1
      patient (3%) and 1 death due to a cerebral hemorrhage (3%) were noted. Response
      rate (RR) was 38% (1 complete and 14 partial responses). Median PFS was 8.6
      months (95% confidence interval [CI], 4.7-10.2 months). Median overall survival
      was 17.2 months (95% CI, 10.4-24.2 months). CONCLUSION: The first US experience
      of capecitabine to our knowledge (3000 mg/m(2) on days 1-7) in combination with
      oxaliplatin/bevacizumab in mCRC does not appear to have advantages compared with
      current standard first-line mCRC treatment regimens.

PMID- 21859565
TI  - Multidisciplinary treatment of brain metastases derived from colorectal cancer
      incorporating stereotactic radiosurgery: analysis of 78 patients.
AB  - BACKGROUND: We investigated the role of radiotherapy, including whole brain
      radiotherapy and stereotactic radiosurgery (SRS), and prognostic factors in
      patients with colorectal cancer (CRC) who developed brain metastases. PATIENTS
      AND METHODS: The data of 78 patients who received multidisciplinary treatment
      from 1996 to 2007 were reviewed. Overall survival (OS), intracerebral control
      (ICC), and local control (LC) were retrospectively analyzed. Six potential
      prognostic factors were evaluated: age, gender, number of brain metastases,
      extracerebral metastases, recursive partitioning analysis (RPA) class, and
      interval from tumor diagnosis to radiotherapy. RESULTS: The median OS and ICC for
      the entire cohort were 8 and 6 months, respectively. Surgical resection
      incorporating treatment resulted in significant improvement in OS (P = .036). On
      multivariate analysis, OS and ICC were significantly correlated with lack of
      extracerebral metastases (P = .024 and P = .041, respectively), lower number of
      lesions (P < .001 and P = .007, respectively) and interval from primary CRC
      diagnosis (P < .001 and .005, respectively) whereas RPA class I-II demonstrated
      significance only for OS (P = .045). SRS-incorporating therapy revealed a 1-year
      LC probability of 85%. No association between LC and any of the potential
      prognostic factors was observed. CONCLUSION: Our data indicate that surgery can
      prolong survival in CRC patients with brain metastases. SRS-incorporating
      treatment provides excellent LC rates and should be considered for patients with
      1-3 lesions. The strong association between survival and the prognostic factors
      identified in this study highlights a patient subset that may potentially benefit
      from new, more aggressive therapies.

PMID- 21859567
TI  - Predicting ulcerative colitis-associated colorectal cancer using reverse
      transcription polymerase chain reaction analysis.
AB  - BACKGROUND: Widespread genetic alterations are present not only in ulcerative
      colitis (UC)-associated neoplastic lesions but also in the adjacent normal
      colonic mucosa. This suggests that genetic changes in nonneoplastic mucosa might
      be effective markers for predicting the development of UC-associated cancer (UC
      Ca). This study aimed to build a predictive model for the development of UC-Ca
      based on gene expression levels measured by reverse-transcription polymerase
      chain reaction (RT-PCR) analysis in nonneoplastic rectal mucosa. PATIENTS AND
      METHODS: Fifty-three UC patients were examined, of which 10 had UC-Ca and 43 did
      not (UC-NonCa). In addition to the 40 genes and transcripts previously shown to
      be predictive for developing UC-Ca in our microarray studies, 149 new genes,
      reported to be important in carcinogenesis, were selected for low density array
      (LDA) analysis. The expression of a total of 189 genes was examined by RT-PCR in
      nonneoplastic rectal mucosa. RESULTS: We identified 20 genes showing differential
      expression in UC-Ca and UC-NonCa patients, including cancer-related genes such as
      CYP27B1, RUNX3, SAMSN1, EDIL3, NOL3, CXCL9, ITGB2, and LYN. Using these 20 genes,
      we were able to build a predictive model that distinguished patients with and
      without UC-Ca with a high accuracy rate of 83% and a negative predictive value of
      100%. CONCLUSION: This predictive model suggests that it is possible to identify
      UC patients at a high risk of developing cancer. These results have important
      implications for improving the efficacy of surveillance by colonoscopy and
      suggest directions for future research into the molecular mechanisms of UC
      associated cancer.

PMID- 21859568
TI  - Mitomycin--C-induced thrombotic thrombocytopenic purpura/hemolytic uremic
      syndrome: cumulative toxicity of an old drug in a new era.
AB  - Mitomycin-C (MMC) is a first-line therapy for anal squamous cell carcinoma
      (ASCC), and it continues to be used for several other indications. Thrombotic
      thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are serious
      complications of MMC therapy. Herein, we describe a 73-year-old woman with
      recurrent ASCC treated with MMC who developed chronic microangiopathic hemolytic
      anemia (MAHA) and thrombocytopenia after receiving a cumulative dose of 50
      mg/m(2). These hematologic adverse events persisted for 9 months and resolved
      after discontinuation of chemotherapy followed by multiple courses of oral
      corticosteroids. This report describes an atypically chronic and mild form of
      secondary TTP/HUS and discusses the possible role of corticosteroids in its
      management.

PMID- 21859566
TI  - Prolonged oxaliplatin exposure alters intracellular calcium signaling: a new
      mechanism to explain oxaliplatin-associated peripheral neuropathy.
AB  - BACKGROUND: Oxaliplatin is a platinum-based cytotoxic agent commonly used to
      treat colorectal cancers. Despite its effectiveness, oxaliplatin administration
      is associated with the development of cold-induced peripheral neuropathy. This
      potentially permanent side effect is provoked by cold exposure and can range from
      mild and self limited to severe and debilitating. Even with tumor shrinkage,
      these painful side effects can force dose reduction or discontinuation of
      treatment. Neither the mechanism of action of oxaliplatin nor that of cold
      induced neuropathy is understood. Paclitaxel, an entirely different
      chemotherapeutic agent used to treat a variety of malignancies, also is
      associated with the development of peripheral neuropathy. Unlike oxaliplatin,
      neurotoxicity arising from paclitaxel treatment was previously found to have
      profound effects on intracellular calcium signaling. METHODS AND RESULTS: In this
      study we examined the effects of oxaliplatin on calcium signaling pathways and
      found that acute exposure of either a neuroblastoma cell line or primary neurons
      with therapeutic concentrations of oxaliplatin had no effect on intracellular
      calcium signaling. We also found that cellular temperature sensors (transient
      receptor potential [TRP] channels) were also not activated by oxaliplatin.
      Interestingly, prolonged exposure of oxaliplatin sensitized cells to subsequent
      stimuli and enhanced the magnitude of intracellular calcium responses.
      CONCLUSIONS: Taken together, our results suggest that acute oxaliplatin exposure
      will not induce abnormal calcium signaling but oxaliplatin-primed cells do
      exhibit enhanced sensitivity. These findings provide new insight to the mechanism
      behind oxaliplatin-induced neuropathy.

PMID- 21859569
TI  - Synchronous epithelial and neuroendocrine cancers of the pancreas: case series of
      a rare occurrence.
AB  - The presence of neuroendocrine cells in adenocarcinomas is not an unusual finding
      and is well described in gastrointestinal tract cancers, eg, colorectal cancer
      and gastric cancer. Genetic analysis of such tumors has suggested a common
      multipotent progenitor stem cell origin. The prognostic significance of
      neuroendocrine cells in adenocarcinoma cells is unclear. There is a scant
      literature on synchronous pancreas ductal adenocarcinoma and pancreas
      neuroendocrine tumors. We report 2 cases with a purpose of discussing management
      strategies, prognosis, and potential etiologies of this rare presentation.

PMID- 21859570
TI  - Comparison between 2-D cross correlation with 2-D sub-sampling and 2-D tracking
      using beam steering.
AB  - We have previously presented multi-dimensional sub-sample motion estimation
      techniques that use multi-dimensional polynomial fitting to the discrete cross
      correlation function to jointly estimate the sub-sample motion in all three
      spatial directions. Previous simulation and experimental results showed that
      these estimators significantly improve the performance of the motion estimation
      in 2-D and 3-D. In this short communication, we present additional simulation
      results and compare these techniques to 2-D tracking using beam steering. The
      results show that beam steering technique performs better in estimating the
      motion vector especially the lateral component.

PMID- 21859571
TI  - High-temperature langasite SAW oxygen sensor.
AB  - High-temperature langasite SAW oxygen sensors using sputtered ZnO as a resistive
      gas-sensing layer were fabricated and tested. Sensitivity to oxygen gas was
      observed between 500 degrees C to 700 degrees C, with a sensitivity peak at about
      625 degrees C, consistent with the theoretical predictions of the acoustoelectric
      effect.

PMID- 21859572
TI  - Differential-mode vibrational noise cancellation structure for
      Metglas/Pb(Zr,Ti)O3 fiber magnetoelectric laminates.
AB  - A differential structure which has the ability to reject external vibrational
      noise for Metglas/Pb(Zr,Ti)O(3) (PZT) fiber-based magnetoelectric (ME)
      heterostructures has been studied. This type of ME structure functions better
      than conventional sensors as a magnetic sensor when used in an environment in
      which vibrational isolation is impractical. Sensors fabricated with this
      differential mode structure can attenuate external vibrational noise by about 10
      to 20 dB at different frequencies, while simultaneously having a doubled ME
      voltage coefficient. Interestingly, in addition to offering a means of mitigating
      vibrational noise, this ME structure offers the potential to be a hybrid sensor,
      separating magnetic and acoustical signals.

PMID- 21859573
TI  - Magnetoelectric bending-mode structure based on Metglas/Pb(Zr,Ti)O3 fiber
      laminates.
AB  - A magnetoelectric (ME) bending-mode structure based on Metglas/Pb(Zr,Ti)O(3)
      fiber laminates has been studied. This bending mode had a fundamental resonance
      (FBR) of about 210 Hz, which was much lower than that of the longitudinal mode.
      Near the FBR, the ME voltage coefficient was about 400 V/cm.Oe. Magnetic sensors
      based on this bending mode had an equivalent magnetic noise floor of <= 0.3
      pT/?Hz at f = 210 Hz.

PMID- 21859574
TI  - The dynamic Allan variance III: confidence and detection surfaces.
AB  - The dynamic Allan variance (DAVAR) is a surface which describes the stability of
      a high-precision clock with respect to time. When the DAVAR is evaluated from
      experimental data, its surface shows random fluctuations caused by the estimation
      process. It is fundamental to assign a statistical significance to these
      fluctuations, so that they can be differentiated from the variations of the
      surface caused by clock anomalies. First, we develop confidence surfaces to
      assign a statistical significance to the random fluctuations of the DAVAR
      estimator. Then, we introduce detection surfaces to reveal the variations of the
      surface caused by clock anomalies. We validate the obtained results through
      numerical simulations.

PMID- 21859575
TI  - Transmit beamforming for optimal second-harmonic generation.
AB  - A simulation study of transmit ultrasound beams from several transducer
      configurations is conducted to compare second-harmonic imaging at 3.5 MHz and 11
      MHz. Second- harmonic generation and the ability to suppress near field echoes
      are compared. Each transducer configuration is defined by a chosen f-number and
      focal depth, and the transmit pressure is estimated to not exceed a mechanical
      index of 1.2. The medium resembles homogeneous muscle tissue with nonlinear
      elasticity and power-law attenuation. To improve computational efficiency, the
      KZK equation is utilized, and all transducers are circular-symmetric. Previous
      literature shows that second-harmonic generation is proportional to the square of
      the transmit pressure, and that transducer configurations with different transmit
      frequencies, but equal aperture and focal depth in terms of wavelengths, generate
      identical second-harmonic fields in terms of shape. Results verify this for a
      medium with attenuation f1. For attenuation f1.1, deviations are found, and the
      high frequency subsequently performs worse than the low frequency. The results
      suggest that high frequencies are less able to suppress near-field echoes in the
      presence of a heterogeneous body wall than low frequencies.

PMID- 21859576
TI  - Lithium niobate transducers for MRI-guided ultrasonic microsurgery.
AB  - Focused ultrasound surgery (FUS) is usually based on frequencies below 5 MHz
      typically around 1 MHz. Although this allows good penetration into tissue, it
      limits the minimum lesion dimensions that can be achieved. In this study, we
      investigate devices to allow FUS at much higher frequencies, in principle,
      reducing the minimum lesion dimensions. Furthermore, FUS can produce deep-sub
      millimeter demarcation between viable and necrosed tissue; high-frequency devices
      may allow this to be exploited in superficial applications which may include
      dermatology, ophthalmology, treatment of the vascular system, and treatment of
      early dysplasia in epithelial tissue. In this paper, we explain the methodology
      we have used to build high-frequency high-intensity transducers using Y-36
      degrees -cut lithium niobate. This material was chosen because its low losses
      give it the potential to allow very-high-frequency operation at harmonics of the
      fundamental operating frequency. A range of single-element transducers with
      center frequencies between 6.6 and 20.0 MHz were built and the transducers'
      efficiency and acoustic power output were measured. A focused 6.6-MHz transducer
      was built with multiple elements operating together and tested using an
      ultrasound phantom and MRI scans. It was shown to increase phantom temperature by
      32 degrees C in a localized area of 2.5 x 3.4 mm in the plane of the MRI scan. Ex
      vivo tests on poultry tissue were also performed and shown to create lesions of
      similar dimensions. This study, therefore, demonstrates that it is feasible to
      produce high-frequency transducers capable of high-resolution FUS using lithium
      niobate.

PMID- 21859577
TI  - A regularization technique for closed contour segmentation in ultrasound images.
AB  - Segmentation of a target object in the form of a closed curve has many potential
      applications in medical imaging because it provides quantitative information
      related to the target objext's size and shape. However, ultrasound image
      segmentation for boundary delineation of the target object is a very difficult
      task because of its inherent drawbacks, including uncertainty of the segmentation
      boundary caused by speckle noise, relatively low SNR, and low contrast. Indeed,
      in automatic ultrasound image segmentation, conventional techniques with standard
      regularization often fail to reach the desired segmentation in the form of a
      simple closed curve because of the weakness of edge detector functions in finding
      the likely target boundary. In this paper, we propose a new regularization model
      which has the property of encouraging a closed curve by deliberately controlling
      the curve smoothness. The new model may be combined with various fitting terms to
      enhance segmentation results. The key features of the proposed model are
      demonstrated in detail. Numerical simulations and experiments show that the
      proposed model enhances the segmentation ability for extracting the target
      boundary as a closed contour.

PMID- 21859578
TI  - Design aspects of focal beams from high-intensity arrays.
AB  - As the applications of ultrasonic thermal therapies expand, the design of the
      high-intensity array must address both the energy delivery of the main beam and
      the character and relevance of off-target beam energy. We simulate the acoustic
      field performance of a selected set of circular arrays organized by array format,
      including flat versus curved arrays, periodic versus random arrays, and center
      void diameter variations. Performance metrics are based on the -3-dB focal main
      lobe (FML) positioning range, axial grating lobe (AGL) temperatures, and side
      lobe levels. Using finite-element analysis, we evaluate the relative heating of
      the FML and the AGLs. All arrays have a maximum diameter of 100lambda, with
      element count ranging from 64 to 1024 and continuous wave frequency of 1.5 MHz.
      First, we show that a 50% spherical annulus produces focus beam side lobes which
      decay as a function of lateral distance at nearly 87% of the exponential rate of
      a full aperture. Second, for the arrays studied, the efficiency of power delivery
      over the -3-dB focus positioning range for spherical arrays is at least 2-fold
      greater than for flat arrays; the 256-element case shows a 5-fold advantage for
      the spherical array. Third, AGL heating can be significant as the focal target is
      moved to its distal half-intensity depth from the natural focus. Increasing the
      element count of a randomized array to 256 elements decreases the AGL-to-FML
      heating ratio to 0.12 at the distal half-intensity depth. Further increases in
      element count yield modest improvements. A 49% improvement in the AGL-to-peak
      heating ratio is predicted by using the Sumanaweera spiral element pattern with
      randomization.

PMID- 21859579
TI  - Monitoring of thermal therapy based on shear modulus changes: II. Shear wave
      imaging of thermal lesions.
AB  - The clinical applicability of high-intensity focused ultrasound (HIFU) for
      noninvasive therapy is currently hampered by the lack of robust and real-time
      monitoring of tissue damage during treatment. The goal of this study is to show
      that the estimation of local tissue elasticity from shear wave imaging (SWI) can
      lead to a precise mapping of the lesion. HIFU treatment and monitoring were
      respectively performed using a confocal setup consisting of a 2.5-MHz single
      element transducer focused at 34 mm on ex vivo samples and an 8-MHz ultrasound
      diagnostic probe. Ultrasound-based strain imaging was combined with shear wave
      imaging on the same device. The SWI sequences consisted of 2 successive shear
      waves induced at different lateral positions. Each wave was created with pushing
      beams of 100 MUs at 3 depths. The shear wave propagation was acquired at 17,000
      frames/s, from which the elasticity map was recovered. HIFU sonications were
      interleaved with fast imaging acquisitions, allowing a duty cycle of more than
      90%. Thus, elasticity and strain mapping was achieved every 3 s, leading to real
      time monitoring of the treatment. When thermal damage occurs, tissue stiffness
      was found to increase up to 4-fold and strain imaging showed strong shrinkages
      that blur the temperature information. We show that strain imaging elastograms
      are not easy to interpret for accurate lesion characterization, but SWI provides
      a quantitative mapping of the thermal lesion. Moreover, the concept of shear wave
      thermometry (SWT) developed in the companion paper allows mapping temperature
      with the same method. Combined SWT and shear wave imaging can map the lesion
      stiffening and temperature outside the lesion, which could be used to predict the
      eventual lesion growth by thermal dose calculation. Finally, SWI is shown to be
      robust to motion and reliable in vivo on sheep muscle.

PMID- 21859580
TI  - Guided waves propagating in a bi-layer system consisting of a piezoelectric plate
      and a dielectric fluid layer.
AB  - This study employs a theoretical modeling and an experimental measurement for
      investigating the dispersion behavior of guided waves propagating in a bi-layer
      system consisting of a piezoelectric plate and a dielectric fluid layer. The
      theoretical model is based on a recursive asymptotic stiffness matrix method
      (RASM) with the fluid layer modeled as an equivalent elastic body. A laser
      ultrasound technique is used to measure the dispersion relations of the bi-layer
      system. Behaviors of mode couplings between guided modes propagating in the
      piezoelectric plate and those in fluid layer are characterized in the modeling
      and measurements. Dispersion behaviors of guided modes propagating in the bi
      layer system are discussed for varying fluid thicknesses. For all of the
      investigated cases, the theoretical modeled dispersion spectra agree well with
      the measurements.

PMID- 21859581
TI  - Scattering of focused ultrasonic beams by two spherical cavities in close
      proximity.
AB  - Ultrasonic fields generated by one and two spherical cavities placed in front of
      a point-focused acoustic lens are modeled by the semi-analytical distributed
      point source method (DPSM). Results are generated by properly considering the
      interaction effect between two cavities placed in the focused ultrasonic field.
      The interaction effect between the two cavities prohibits the linear
      superposition of single cavity solutions to obtain the solution for two cavities
      placed in close proximity. Therefore, although some analytical and semi
      analytical solutions are available for the single cavity in a focused ultrasonic
      field, those solutions cannot be simply superimposed for solving the two-cavity
      problem even for a linear elastic material. Solution of this problem is necessary
      to evaluate when two cavities placed in close proximity can be distinguished by
      an acoustic lens and when it is not possible. The comparison between the
      reflections of ultrasonic energy from two small cavities versus a single big
      cavity is also investigated.

PMID- 21859582
TI  - The torsional waveguide viscosity probe: design and anomalous behavior.
AB  - This paper is concerned with the design of viscosity sensors based on a torsional
      waveguide. The advantages of using guided wave attenuation instead of speed for
      viscosity estimation are established. The effects of probe material, dimensions,
      and operating frequency on viscosity measurement are discussed in the context of
      a requirement to match the measured attenuation to the range of viscosity values
      that are to be measured, given the constraints on measurability imposed by the
      overall signal and noise conditions. A prototype probe is shown to work well with
      Newtonian liquids but to appreciably underestimate the viscosities of polymeric
      oils; these anomalies are explained quantitatively on the basis of a model of
      intramolecular relaxation. The probe was unsuccessful when applied to slurries,
      and a basic explanation is given.

PMID- 21859583
TI  - Performance evaluation of dual-frequency driving plate ultrasonic motor based on
      an analytical model.
AB  - An analytical model is presented to explain the effects of dual-frequency drive
      on the plate ultrasonic motor in this paper. The experimental prototype is a
      plate ultrasonic motor using single-phase asymmetric excitation, which can work
      under a single vibration or multiple vibration modes. Based on the linear
      superposition of vibrations with two different excitation frequencies, an
      analytical model is established using the classic Coulomb friction model, and the
      non-load rotation speed and maximum stall torque are deduced. Moreover, some
      crucial parameters such as preload and dead-zone in dual-frequency superposition
      model are identified or modified automatically by searching for the maximum
      correlation coefficient between simulation and experimental data using single
      frequency drive. It is found that simulation and experiment results agree well
      when no excitation frequency component is at resonance.

PMID- 21859584
TI  - Airborne ultrasonic vortex generation using flexible ferroelectrets.
AB  - Cellular ferroelectrets exhibit interesting electromechanical- acoustical
      characteristics. Their recent appearance and remarkable properties open up new
      possibilities for the design and development of ultrasonic transducers. In
      particular, the feasibility of fabricating ultrasonic vortex generators using
      ferroelectret films is demonstrated in this work. To this end, a transducer
      prototype was built by gluing the material onto a tangential-helical surface
      (outer diameter: 40 mm, pitch: 3.45 mm). Experimental results agree well with the
      theoretical estimation of the pressure and phase of the acoustic field in the
      near field and far field, which corroborates the potential of ferroelectrets to
      customize special acoustic fields. Furthermore, the proposed fabrication
      procedure is inexpensive and represents a new alternative for exploring and
      analyzing the special characteristics of acoustical helical wavefronts.

PMID- 21859585
TI  - Front-end receiver electronics for high-frequency monolithic CMUT-on-CMOS imaging
      arrays.
AB  - This paper describes the design of CMOS receiver electronics for monolithic
      integration with capacitive micromachined ultrasonic transducer (CMUT) arrays for
      highfrequency intravascular ultrasound imaging. A custom 8-inch (20-cm) wafer is
      fabricated in a 0.35-MUm two-poly, four-metal CMOS process and then CMUT arrays
      are built on top of the application specific integrated circuits (ASICs) on the
      wafer. We discuss advantages of the single-chip CMUT-on-CMOS approach in terms of
      receive sensitivity and SNR. Low-noise and high-gain design of a transimpedance
      amplifier (TIA) optimized for a forward-looking volumetric-imaging CMUT array
      element is discussed as a challenging design example. Amplifier gain, bandwidth,
      dynamic range, and power consumption trade-offs are discussed in detail. With
      minimized parasitics provided by the CMUT-on-CMOS approach, the optimized TIA
      design achieves a 90 fA/?Hz input-referred current noise, which is less than the
      thermal-mechanical noise of the CMUT element. We show successful system operation
      with a pulseecho measurement. Transducer-noise-dominated detection in immersion
      is also demonstrated through output noise spectrum measurement of the integrated
      system at different CMUT bias voltages. A noise figure of 1.8 dB is obtained in
      the designed CMUT bandwidth of 10 to 20 MHz.

PMID- 21859586
TI  - Frequency dispersion of longitudinal ultrasonic velocity and attenuation in
      [001]c-poled 0.24Pb(In1/2Nb1/2O3- 0.45Pb(Mg1/3Nb2/3)O3-0.31PbTiO3 single crystal.
AB  - The frequency dispersion of ultrasonic velocity and attenuation in [001](c)-poled
      0.24Pb(in(1/2)Nb(1/2))O(3)-0.45Pb(Mg(1/3)Nb(2/3))o(3)-0.31PbTio(3) (PIN-0.45PMN
      0.31PT) ternary single crystal were measured by ultrasonic spectroscopy from 25
      to 100 MHz for the longitudinal wave. It was found that the velocity has a linear
      relationship with the frequency f, but the attenuation has a quadratic relation
      with f. The attenuation and frequency dispersion of the ternary system are lower
      than that of the (1-x)Pb(Mg(1/3)Nb(2/3))O(3)-xPbTiO(3) (PMN-PT) binary system and
      the coercive field also increased by a factor of 2.5, hence, the ternary single
      system is superior to the corresponding binary single-crystal system for high
      frequency and high-power transducer applications.

PMID- 21859587
TI  - Matrix method for acoustic levitation simulation.
AB  - A matrix method is presented for simulating acoustic levitators. A typical
      acoustic levitator consists of an ultrasonic transducer and a reflector. The
      matrix method is used to determine the potential for acoustic radiation force
      that acts on a small sphere in the standing wave field produced by the levitator.
      The method is based on the Rayleigh integral and it takes into account the
      multiple reflections that occur between the transducer and the reflector. The
      potential for acoustic radiation force obtained by the matrix method is validated
      by comparing the matrix method results with those obtained by the finite element
      method when using an axisymmetric model of a single-axis acoustic levitator.
      After validation, the method is applied in the simulation of a noncontact
      manipulation system consisting of two 37.9-kHz Langevin-type transducers and a
      plane reflector. The manipulation system allows control of the horizontal
      position of a small levitated sphere from -6 mm to 6 mm, which is done by
      changing the phase difference between the two transducers. The horizontal
      position of the sphere predicted by the matrix method agrees with the horizontal
      positions measured experimentally with a charge-coupled device camera. The main
      advantage of the matrix method is that it allows simulation of non-symmetric
      acoustic levitators without requiring much computational effort.

PMID- 21859588
TI  - Correlation between temperature coefficient of elasticity and fourier transform
      infrared spectra of silicon dioxide films for surface acoustic wave devices.
AB  - We investigated the correlation between the temperature coefficient of elasticity
      (TCE) and Fourier transform infrared (FT-IR) absorption spectra of SiO(2) for SAW
      devices. The measurement indicated that the TCE is strongly correlated with peak
      frequencies; that is, with the fractional change of the Si-O-Si bond angle with
      temperature.

PMID- 21859589
TI  - Deep-UV sensors based on SAW oscillators using low-temperature-grown AlN films on
      sapphires.
AB  - High-quality epitaxial AlN films were deposited on sapphire substrates at low
      growth temperature using a helicon sputtering system. SAW filters fabricated on
      the AlN films exhibited excellent characteristics, with center frequency of 354.2
      MHz, which corresponds to a phase velocity of 5667 m/s. An oscillator fabricated
      using AlN-based SAW devices is presented and applied to deep-UV light detection.
      A frequency downshift of about 43 KHz was observed when the surface of SAW device
      was illuminated by a UV source with dominant wavelength of around 200 nm. The
      results indicate the feasibility of developing remote sensors for deep-UV
      measurement using AlN-based SAW oscillators.

PMID- 21859590
TI  - Unprecedented long-term frequency stability with a microwave resonator
      oscillator.
AB  - This article reports on the long-term frequency stability characterization of a
      new type of cryogenic sapphire oscillator using an autonomous pulse-tube
      cryocooler as its cold source. This new design enables a relative frequency
      stability of better than 4.5 x 10(-15) over one day of integration. To the best
      of our knowledge, this represents the best long-term frequency stability ever
      obtained with a signal source based on a macroscopic resonator.

PMID- 21859591
TI  - GPU-based beamformer: fast realization of plane wave compounding and synthetic
      aperture imaging.
AB  - Although they show potential to improve ultrasound image quality, plane wave (PW)
      compounding and synthetic aperture (SA) imaging are computationally demanding and
      are known to be challenging to implement in real-time. In this work, we have
      developed a novel beamformer architecture with the real-time parallel processing
      capacity needed to enable fast realization of PW compounding and SA imaging. The
      beamformer hardware comprises an array of graphics processing units (GPUs) that
      are hosted within the same computer workstation. Their parallel computational
      resources are controlled by a pixel-based software processor that includes the
      operations of analytic signal conversion, delay-and-sum beamforming, and
      recursive compounding as required to generate images from the channel-domain data
      samples acquired using PW compounding and SA imaging principles. When using two
      GTX-480 GPUs for beamforming and one GTX-470 GPU for recursive compounding, the
      beamformer can compute compounded 512 x 255 pixel PW and SA images at throughputs
      of over 4700 fps and 3000 fps, respectively, for imaging depths of 5 cm and 15 cm
      (32 receive channels, 40 MHz sampling rate). Its processing capacity can be
      further increased if additional GPUs or more advanced models of GPU are used.

PMID- 21859593
TI  - In vitro identification of four-element windkessel models based on iterated
      unscented Kalman filter.
AB  - Mock circulatory loops (MCLs) have been widely used to test left ventricular
      assist devices. The hydraulic properties of the mock systemic arterial system are
      usually described by two alternative four-element windkessel (W4) models.
      Compared with three-element windkessel model, their parameters, especially the
      inertial term, are much more difficult to estimate. In this paper, an estimator
      based on the iterated unscented Kalman filter (IUKF) algorithm is proposed to
      identify model parameters. Identifiability of these parameters for different
      measurements is described. Performance of the estimator for different model
      structures is first evaluated using numerical simulation data contaminated with
      artificial noise. An MCL is developed to test the proposed algorithm. Parameter
      estimates for different models are compared with the calculated values derived
      from the mechanical and hydraulic properties of the MCL to validate model
      structures. In conclusion, the W4 model with an inertance and an aortic
      characteristic resistance arranged in series is proposed to represent the mock
      systemic arterial system. Once model structure is appropriately selected, IUKF
      can provide reasonable estimation accuracy in a limited time and may be helpful
      for future clinical applications.

PMID- 21859594
TI  - Enhancing impedance imaging through multimodal tomography.
AB  - Several noninvasive modalities including electrical impedance tomography (EIT),
      magnetic induction tomography (MIT), and induced-current EIT (ICEIT) have been
      developed for imaging the electrical conductivity distribution within a human
      body. Although these modalities differ in how the excitation and detection
      circuitry (electrodes or coils) are implemented, they share a number of common
      principles not only within the image reconstruction approaches but also with
      respect to the basic principle of generating a current density distribution
      inside a body and recording the resultant electric fields. In this paper, we are
      interested in comparing differences between these modalities and in theoretically
      understanding the compromises involved, despite the increased hardware cost and
      complexity that such a multimodal system brings along. To systematically assess
      the merits of combining data, we performed 3-D simulations for each modality and
      for the multimodal system by combining all available data. The normalized
      sensitivity matrices were computed for each modality based on the finite element
      method, and singular value decomposition was performed on the resultant matrices.
      We used both global and regional quality measures to evaluate and compare
      different modalities. This study has shown that the condition number of the
      sensitivity matrix obtained from the multimodal tomography with 16-electrode and
      16-coil is much lower than the condition number produced in the conventional 16
      channel EIT and MIT systems, and thus, produced promising results in terms of
      image stability. An improvement of about 20% in image resolution can be achieved
      considering feasible signal-to-noise ratio levels.

PMID- 21859595
TI  - A hermetic wireless subretinal neurostimulator for vision prostheses.
AB  - A miniaturized, hermetically encased, wirelessly operated retinal prosthesis has
      been developed for preclinical studies in the Yucatan minipig, and includes
      several design improvements over our previously reported device. The prosthesis
      attaches conformally to the outside of the eye and electrically drives a
      microfabricated thin-film polyimide array of sputtered iridium oxide film
      electrodes. This array is implanted into the subretinal space using a customized
      ab externo surgical technique. The implanted device includes a hermetic titanium
      case containing a 15-channel stimulator chip and discrete circuit components.
      Feedthroughs in the case connect the stimulator chip to secondary power and data
      receiving coils on the eye and to the electrode array under the retina. Long-term
      in vitro pulse testing of the electrodes projected a lifetime consistent with
      typical devices in industry. The final assembly was tested in vitro to verify
      wireless operation of the system in physiological saline using a custom RF
      transmitter and primary coils. Stimulation pulse strength, duration, and
      frequency were programmed wirelessly from a Peripheral Component Interconnect
      eXtensions for Instrumentation (PXI) computer. Operation of the retinal implant
      has been verified in two pigs for up to five and a half months by detecting
      stimulus artifacts generated by the implanted device.

PMID- 21859596
TI  - Analysis of FMRI data using an integrated principal component analysis and
      supervised affinity propagation clustering approach.
AB  - Clustering analysis is a promising data-driven method for analyzing functional
      magnetic resonance imaging (fMRI) time series data. The huge computational load,
      however, creates practical difficulties for this technique. We present a novel
      approach, integrating principal component analysis (PCA) and supervised affinity
      propagation clustering (SAPC). In this method, fMRI data are initially processed
      by PCA to obtain a preliminary image of brain activation. SAPC is then used to
      detect different brain functional activation patterns. We used a supervised
      Silhouette index to optimize clustering quality and automatically search for the
      optimal parameter  p in SAPC, so that the basic affinity propagation clustering
      is improved by applying SAPC. Four simulation studies and tests with three in
      vivo fMRI datasets containing data from both block-design and event-related
      experiments revealed that functional brain activation was effectively detected
      and different response patterns were distinguished using our integrated method.
      In addition, the improved SAPC method was superior to the  k -centers clustering
      and hierarchical clustering methods in both block-design and event-related fMRI
      data, as measured by the average squared error. These results suggest that our
      proposed novel integrated approach will be useful for detecting brain functional
      activation in both block-design and event-related experimental fMRI data.

PMID- 21859597
TI  - Design and control of a demand flow system assuring spontaneous breathing of a
      patient connected to an HFO ventilator.
AB  - Lung protective ventilation is intended to minimize the risk of ventilator
      induced lung injury and currently aimed at preservation of spontaneous breathing
      during mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is a
      lung protective ventilation strategy. Commonly used high-frequency oscillatory
      (HFO) ventilators, SensorMedics 3100, were not designed to tolerate spontaneous
      breathing. Respiratory efforts in large pediatric and adult patients impose a
      high workload to the patient and may cause pressure swings that impede ventilator
      function. A Demand Flow System (DFS) was designed to facilitate spontaneous
      breathing during HFOV. Using a linear quadratic Gaussian state feedback
      controller, the DFS alters the inflow of gas into the ventilator circuit, so that
      it instantaneously compensates for the changes in mean airway pressure (MAP) in
      the ventilator circuit caused by spontaneous breathing. The undesired swings in
      MAP are thus eliminated. The DFS significantly reduces the imposed work of
      breathing and improves ventilator function. In a bench test the performance of
      the DFS was evaluated using a simulator ASL 5000. With the gas inflow controlled,
      MAP was returned to its preset value within 115 ms after the beginning of
      inspiration. The DFS might help to spread the use of HFOV in clinical practice.

PMID- 21859598
TI  - Inter-individual differences in fMRI entropy measurements in old age.
AB  - We investigated the association between individual differences in cognitive
      performance in old age and the approximate entropy (ApEn) measured from
      functional magnetic resonance imaging (fMRI) data acquired from 40 participants
      of the Aberdeen Birth Cohort 1936 (ABC1936), while undergoing a visual
      information processing task: inspection time (IT). Participants took a version of
      the Moray House Test (MHT) No. 12 at age 11, a valid measure of childhood
      intelligence. The same individuals completed a test of non-verbal reasoning
      (Raven's Standard Progressive Matrices [RPM]) aged about 68 years. The IT, MHT
      and RPM scores were used as indicators of cognitive performance. Our results show
      that higher regional signal entropy is associated with better cognitive
      performance. This finding was independent of ability in childhood but not
      independent of current cognitive ability. ApEn is used for the first time to
      identify a potential source of individual differences in cognitive ability using
      fMRI data.

PMID- 21859599
TI  - Object tracking with particle filtering in fluorescence microscopy images:
      application to the motion of neurofilaments in axons.
AB  - Neurofilaments are long flexible cytoplasmic protein polymers that are
      transported rapidly but intermittently along the axonal processes of nerve cells.
      Current methods for studying this movement involve manual tracking of
      fluorescently tagged neurofilament polymers in videos acquired by time-lapse
      fluorescence microscopy. Here, we describe an automated tracking method that uses
      particle filtering to implement a recursive Bayesian estimation of the filament
      location in successive frames of video sequences. To increase the efficiency of
      this approach, we take advantage of the fact that neurofilament movement is
      confined within the boundaries of the axon. We use piecewise cubic spline
      interpolation to model the path of the axon and then we use this model to limit
      both the orientation and location of the neurofilament in the particle tracking
      algorithm. Based on these two spatial constraints, we develop a prior dynamic
      state model that generates significantly fewer particles than generic particle
      filtering, and we select an adequate observation model to produce a robust
      tracking method. We demonstrate the efficacy and efficiency of our method by
      performing tracking experiments on real time-lapse image sequences of
      neurofilament movement, and we show that the method performs well compared to
      manual tracking by an experienced user. This spatially constrained particle
      filtering approach should also be applicable to the movement of other axonally
      transported cargoes.

PMID- 21859600
TI  - A new formulation for feedforward neural networks.
AB  - Feedforward neural network is one of the most commonly used function
      approximation techniques and has been applied to a wide variety of problems
      arising from various disciplines. However, neural networks are black-box models
      having multiple challenges/difficulties associated with training and
      generalization. This paper initially looks into the internal behavior of neural
      networks and develops a detailed interpretation of the neural network functional
      geometry. Based on this geometrical interpretation, a new set of variables
      describing neural networks is proposed as a more effective and geometrically
      interpretable alternative to the traditional set of network weights and biases.
      Then, this paper develops a new formulation for neural networks with respect to
      the newly defined variables; this reformulated neural network (ReNN) is
      equivalent to the common feedforward neural network but has a less complex error
      response surface. To demonstrate the learning ability of ReNN, in this paper, two
      training methods involving a derivative-based (a variation of backpropagation)
      and a derivative-free optimization algorithms are employed. Moreover, a new
      measure of regularization on the basis of the developed geometrical
      interpretation is proposed to evaluate and improve the generalization ability of
      neural networks. The value of the proposed geometrical interpretation, the ReNN
      approach, and the new regularization measure are demonstrated across multiple
      test problems. Results show that ReNN can be trained more effectively and
      efficiently compared to the common neural networks and the proposed
      regularization measure is an effective indicator of how a network would perform
      in terms of generalization.

PMID- 21859601
TI  - A fast majorize-minimize algorithm for the recovery of sparse and low-rank
      matrices.
AB  - We introduce a novel algorithm to recover sparse and low-rank matrices from noisy
      and undersampled measurements. We pose the reconstruction as an optimization
      problem, where we minimize a linear combination of data consistency error,
      nonconvex spectral penalty, and nonconvex sparsity penalty. We majorize the
      nondifferentiable spectral and sparsity penalties in the criterion by quadratic
      expressions to realize an iterative three-step alternating minimization scheme.
      Since each of these steps can be evaluated either analytically or using fast
      schemes, we obtain a computationally efficient algorithm. We demonstrate the
      utility of the algorithm in the context of dynamic magnetic resonance imaging
      (MRI) reconstruction from sub-Nyquist sampled measurements. The results show a
      significant improvement in signal-to-noise ratio and image quality compared with
      classical dynamic imaging algorithms. We expect the proposed scheme to be useful
      in a range of applications including video restoration and multidimensional MRI.

PMID- 21859602
TI  - Rate-distortion analysis of directional wavelets.
AB  - The inefficiency of separable wavelets in representing smooth edges has led to a
      great interest in the study of new 2-D transformations. The most popular
      criterion for analyzing these transformations is the approximation power.
      Transformations with near-optimal approximation power are useful in many
      applications such as denoising and enhancement. However, they are not necessarily
      good for compression. Therefore, most of the nearly optimal transformations such
      as curvelets and contourlets have not found any application in image compression
      yet. One of the most promising schemes for image compression is the elegant idea
      of directional wavelets (DIWs). While these algorithms outperform the state-of
      the-art image coders in practice, our theoretical understanding of them is very
      limited. In this paper, we adopt the notion of rate-distortion and calculate the
      performance of the DIW on a class of edge-like images. Our theoretical analysis
      shows that if the edges are not "sharp," the DIW will compress them more
      efficiently than the separable wavelets. It also demonstrates the inefficiency of
      the quadtree partitioning that is often used with the DIW. To solve this issue,
      we propose a new partitioning scheme called megaquad partitioning. Our simulation
      results on real-world images confirm the benefits of the proposed partitioning
      algorithm, promised by our theoretical analysis.

PMID- 21859603
TI  - Feature-specific difference imaging.
AB  - Difference images quantify changes in the object scene over time. In this paper,
      we use the feature-specific imaging paradigm to present methods for estimating a
      sequence of difference images from a sequence of compressive measurements of the
      object scene. Our goal is twofold. First is to design, where possible, the
      optimal sensing matrix for taking compressive measurements. In scenarios where
      such sensing matrices are not tractable, we consider plausible candidate sensing
      matrices that either use the available a priori information or are nonadaptive.
      Second, we develop closed-form and iterative techniques for estimating the
      difference images. We specifically look at l(2)- and l(1)-based methods. We show
      that l(2)-based techniques can directly estimate the difference image from the
      measurements without first reconstructing the object scene. This direct
      estimation exploits the spatial and temporal correlations between the object
      scene at two consecutive time instants. We further develop a method to estimate a
      generalized difference image from multiple measurements and use it to estimate
      the sequence of difference images. For l(1)-based estimation, we consider
      modified forms of the total-variation method and basis pursuit denoising. We also
      look at a third method that directly exploits the sparsity of the difference
      image. We present results to show the efficacy of these techniques and discuss
      the advantages of each.

PMID- 21859604
TI  - Data mining to generate adverse drug events detection rules.
AB  - Adverse drug events (ADEs) are a public health issue. Their detection usually
      relies on voluntary reporting or medical chart reviews. The objective of this
      paper is to automatically detect cases of ADEs by data mining. 115,447 complete
      past hospital stays are extracted from six French, Danish, and Bulgarian
      hospitals using a common data model including diagnoses, drug administrations,
      laboratory results, and free-text records. Different kinds of outcomes are
      traced, and supervised rule induction methods (decision trees and association
      rules) are used to discover ADE detection rules, with respect to time
      constraints. The rules are then filtered, validated, and reorganized by a
      committee of experts. The rules are described in a rule repository, and several
      statistics are automatically computed in every medical department, such as the
      confidence, relative risk, and median delay of outcome appearance. 236 validated
      ADE-detection rules are discovered; they enable to detect 27 different kinds of
      outcomes. The rules use a various number of conditions related to laboratory
      results, diseases, drug administration, and demographics. Some rules involve
      innovative conditions, such as drug discontinuations.

PMID- 21859605
TI  - Carbon nanotube yarns for deep brain stimulation electrode.
AB  - A new form of deep brain stimulation (DBS) electrode was proposed that was made
      of carbon nanotube yarns (CNTYs). Electrode interface properties were examined
      using cyclic voltammetry (CV) and electrochemical impedance spectrum (EIS). The
      CNTY electrode interface exhibited large charge storage capacity (CSC) of 12.3
      mC/cm(2) which increased to 98.6 mC/cm(2) after acid treatment, compared with 5.0
      mC/cm(2) of Pt-Ir. Impedance spectrum of both untreated and treated CNTY
      electrodes showed that finite diffusion process occurred at the interface due to
      their porous structure and charge was delivered through capacitive mechanism. To
      evaluate stability electrical stimulus was exerted for up to 72 h and CV and EIS
      results of CNTY electrodes revealed little alteration. Therefore CNTY could make
      a good electrode material for DBS.

PMID- 21859606
TI  - A bilateral ankle manipulator to investigate human balance control.
AB  - The ankles play an important role in human balance. In most studies investigating
      balance control the contribution of the left and right leg is not separated.
      However, in certain pathologies such as stroke and Parkinson's disease, balance
      control can be asymmetric. Here, a bilateral ankle perturbator (BAP) is
      presented, which applies support surface rotations to both ankles independently.
      The device consists of two small foot-size support surfaces, which are
      independently actuated. The BAP device can operate in either angle or torque
      control mode. The device is able to apply support surface rotations up to 8.6
      degrees  with a bandwidth of 42 Hz. Additionally the platforms can be replaced by
      6-DoF force plates to measure the center of pressure underneath each foot. With
      the optional force plates the bandwidth decreases to 16 Hz as a result of the
      additional weight. Two possible applications of the device to investigate human
      balance control are demonstrated: ankle stiffness by applying minimum jerk
      profiles and sensory reweighting of the proprioceptive information. In
      conclusion, we developed a bilateral ankle perturbator which is able to apply
      support surface rotations to both ankles independently. The major application of
      the device will be to investigate the contribution of both ankles to human
      balance control, and the interactions in balance control between both legs.

PMID- 21859607
TI  - Object discrimination with an artificial hand using electrical stimulation of
      peripheral tactile and proprioceptive pathways with intrafascicular electrodes.
AB  - Trans-radial amputee subjects were implanted with intrafascicular electrodes in
      the stumps of the median and ulnar nerves. Electrical stimulation through these
      electrodes was used to provide sensations of touch and finger position referred
      to the amputated hand. Two subjects were asked to identify different objects as
      to size and stiffness by manipulating them with a myo-electric hand without
      visual or auditory cues. Both subjects were provided with information about
      contact force with the objects via tactile sensations referred to their phantom
      hands. One subject, who was provided with information about finger position in
      the prosthetic hand via a different tactile sensation referred to his phantom
      hand, was unable to correctly identify the objects. The other subject, who
      received information about finger position via a proprioceptive sensation
      referred to his phantom hand, correctly identified the objects at a level
      statistically significantly above chance performance.

PMID- 21859608
TI  - An analysis of the accuracy of wearable sensors for classifying the causes of
      falls in humans.
AB  - Falls are the number one cause of injury in older adults. Wearable sensors,
      typically consisting of accelerometers and/or gyroscopes, represent a promising
      technology for preventing and mitigating the effects of falls. At present, the
      goal of such "ambulatory fall monitors" is to detect the occurrence of a fall and
      alert care providers to this event. Future systems may also provide information
      on the causes and circumstances of falls, to aid clinical diagnosis and targeting
      of interventions. As a first step towards this goal, the objective of the current
      study was to develop and evaluate the accuracy of a wearable sensor system for
      determining the causes of falls. Sixteen young adults participated in
      experimental trials involving falls due to slips, trips, and "other" causes of
      imbalance. Three-dimensional acceleration data acquired during the falling trials
      were input to a linear discriminant analysis technique. This routine achieved 96%
      sensitivity and 98% specificity in distinguishing the causes of a falls using
      acceleration data from three markers (left ankle, right ankle, and sternum). In
      contrast, a single marker provided 54% sensitivity and two markers provided 89%
      sensitivity. These results indicate the utility of a three-node accelerometer
      array for distinguishing the cause of falls.

PMID- 21859609
TI  - Interaction of specialized cardiac conduction system with antiarrhythmic drugs: a
      simulation study.
AB  - The use of antiarrhythmic drugs is common to treat heart rhythm disorders.
      Computational modeling and simulation are promising tools that could be used to
      investigate the effects of specific drugs on cardiac electrophysiology. In this
      paper, we study the multiscale effects of dofetilide, a drug that blocks IKr,
      from cellular to organ level paying special attention to its effect on heart
      structures, in particular the specialized cardiac conduction system (CCS). We
      include a model of the CCS in a patient-specific anatomical ventricular model and
      study the drug effects in simulations with and without a CCS. Results confirmed
      the expected effects of dofetilide at cellular level, increasing the action
      potential duration, and at organ level, prolonging the QT segment. Notable
      differences are shown between models with and without the CCS on action potential
      duration distributions. These techniques show the importance of heart
      heterogeneity and the global effects of the interaction of drugs with cardiac
      structures.

PMID- 21859610
TI  - A multiscale model of atherosclerotic plaque formation at its early stage.
AB  - A multiscale model of atherosclerotic plaque formation at its early stage has
      been developed in order to integrate the various phenomena leading to fatty
      streak formation. The different scales considered in this model are in both the
      spatial domain (from cellular to organism level) and the time domain (from
      seconds to months). The cellular level was considered by modeling the transport
      and chemical interactions of low-density lipoproteins (LDL) and other agents in a
      stenosed artery. This was linked to arterial thickening (organ level). Mean blood
      LDL level (organism level) was selected as one of the critical factors for
      atherosclerotic formation along with wall shear stress (WSS) exerted on the
      endothelium (the inner portion of the artery). It was observed that plaque
      location was dependent on WSS and that plaque size, number, and growth was
      dependent on mean blood LDL levels as well.

PMID- 21859611
TI  - The maximal downstroke of epicardial potentials as an index of electrical
      activity in mouse hearts.
AB  - The maximal upstroke of transmembrane voltage (dV(m)/dt(max)) has been used as an
      indirect measure of sodium current I(Na) upon activation in cardiac myocytes.
      However, sodium influx generates not only the upstroke of V(m), but also the
      downstroke of the extracellular potentials V(e) including epicardial surface
      potentials V(es). The purpose of this study was to evaluate the magnitude of the
      maximal downstroke of V(es) (|dV(es)/dt (min)|) as a global index of electrical
      activation, based on the relationship of dV(m)/dt(max) to I(Na). To fulfill this
      purpose, we examined |dV(es)/dt(min)| experimentally using isolated perfused
      mouse hearts and computationally using a 3-D cardiac tissue bidomain model. In
      experimental studies, a custom-made cylindrical "cage" array with 64 electrodes
      was slipped over mouse hearts to measure V(es) during hyperkalemia, ischemia, and
      hypoxia, which are conditions that decrease I(Na). Values of |dV(es)/dt(min)|
      from each electrode were normalized (|dV(es)/dt (min)|(n)) and averaged
      (|dV(es)/dt(min)|(na)). Results showed that |dV(es)/dt(min)|(na) decreased during
      hyperkalemia by 28, 59, and 79% at 8, 10, and 12 mM [K(+)](o), respectively.
      |dV(es)/dt(min)| also decreased by 54 and 84% 20 min after the onset of ischemia
      and hypoxia, respectively. In computational studies, |dV(es)/dt(min)| was
      compared to dV(m)/dt(max) at different levels of the maximum sodium conductance
      G(Na), extracellular potassium ion concentration [K(+)](o), and intracellular
      sodium ion concentration [Na(+)](i), which all influence levels of I(Na). Changes
      in |dV(es)/dt(min)|(n) were similar to dV(m)/dt (max) during alterations of
      G(Na), [K(+)](o), and [Na(+)](i). Our results demonstrate that
      |dV(es)/dt(min)|(na) is a robust global index of electrical activation for use in
      mouse hearts and, similar to dV(m)/dt(max), can be used to probe
      electrophysiological alterations reliably. The index can be readily measured and
      evaluated, which makes it attractive for characterization of, for instance,
      genetically modified mouse hearts and drug effects on cardiac tissue.

PMID- 21859612
TI  - Robust Student's-t mixture model with spatial constraints and its application in
      medical image segmentation.
AB  - Finite mixture model based on the Student's-t distribution, which is heavily
      tailed and more robust than Gaussian, has recently received great attention for
      image segmentation. A new finite Student's-t mixture model (SMM) is proposed in
      this paper. Existing models do not explicitly incorporate the spatial
      relationships between pixels. First, our model exploits Dirichlet distribution
      and Dirichlet law to incorporate the local spatial constrains in an image.
      Secondly, we directly deal with the Student's-t distribution in order to estimate
      the model parameters, whereas, the Student's-t distributions in previous models
      are represented as an infinite mixture of scaled Gaussians that lead to an
      increase in complexity. Finally, instead of using expectation maximization (EM)
      algorithm, the proposed method adopts the gradient method to minimize the higher
      bound on the data negative log-likelihood and to optimize the parameters. The
      proposed model is successfully compared to the state-of-the-art finite mixture
      models. Numerical experiments are presented where the proposed model is tested on
      various simulated and real medical images.

PMID- 21859614
TI  - Motion tracking for medical imaging: a nonvisible structured light tracking
      approach.
AB  - We present a system for head motion tracking in 3D brain imaging. The system is
      based on facial surface reconstruction and tracking using a structured light (SL)
      scanning principle. The system is designed to fit into narrow 3D medical scanner
      geometries limiting the field of view. It is tested in a clinical setting on the
      high resolution research tomograph (HRRT), Siemens PET scanner with a head
      phantom and volunteers. The SL system is compared to a commercial optical
      tracking system, the Polaris Vicra system, from NDI based on translatory and
      rotary ground truth motions of the head phantom. The accuracy of the systems was
      similar, with root mean square (rms) errors of 0.09 degrees for +/-20 degrees
      axial rotations, and rms errors of 0.24 mm for +/- 25 mm translations. Tests were
      made using (1) a light emitting diode (LED) based miniaturized video projector,
      the Pico projector from Texas Instruments, and (2) a customized version of this
      projector replacing a visible light LED with a 850 nm near infrared LED. The
      latter system does not provide additional discomfort by visible light projection
      into the patient's eyes. The main advantage over existing head motion tracking
      devices, including the Polaris Vicra system, is that it is not necessary to place
      markers on the patient. This provides a simpler workflow and eliminates
      uncertainties related to marker attachment and stability. We show proof of
      concept of a marker less tracking system especially designed for clinical use
      with promising results.

PMID- 21859615
TI  - Texture-based analysis of COPD: a data-driven approach.
AB  - This study presents a fully automatic, data-driven approach for texture-based
      quantitative analysis of chronic obstructive pulmonary disease (COPD) in
      pulmonary computed tomography (CT) images. The approach uses supervised learning
      where the class labels are, in contrast to previous work, based on measured lung
      function instead of on manually annotated regions of interest (ROIs). A
      quantitative measure of COPD is obtained by fusing COPD probabilities computed in
      ROIs within the lung fields where the individual ROI probabilities are computed
      using a k nearest neighbor (kNN ) classifier. The distance between two ROIs in
      the kNN classifier is computed as the textural dissimilarity between the ROIs,
      where the ROI texture is described by histograms of filter responses from a multi
      scale, rotation invariant Gaussian filter bank. The method was trained on 400
      images from a lung cancer screening trial and subsequently applied to classify
      200 independent images from the same screening trial. The texture-based measure
      was significantly better at discriminating between subjects with and without COPD
      than were the two most common quantitative measures of COPD in the literature,
      which are based on density. The proposed measure achieved an area under the
      receiver operating characteristic curve (AUC) of 0.713 whereas the best
      performing density measure achieved an AUC of 0.598. Further, the proposed
      measure is as reproducible as the density measures, and there were indications
      that it correlates better with lung function and is less influenced by
      inspiration level.

PMID- 21859613
TI  - Estimation of mouse organ locations through registration of a statistical mouse
      atlas with micro-CT images.
AB  - Micro-CT is widely used in preclinical studies of small animals. Due to the low
      soft-tissue contrast in typical studies, segmentation of soft tissue organs from
      noncontrast enhanced micro-CT images is a challenging problem. Here, we propose
      an atlas-based approach for estimating the major organs in mouse micro-CT images.
      A statistical atlas of major trunk organs was constructed based on 45 training
      subjects. The statistical shape model technique was used to include inter-subject
      anatomical variations. The shape correlations between different organs were
      described using a conditional Gaussian model. For registration, first the high
      contrast organs in micro-CT images were registered by fitting the statistical
      shape model, while the low-contrast organs were subsequently estimated from the
      high-contrast organs using the conditional Gaussian model. The registration
      accuracy was validated based on 23 noncontrast-enhanced and 45 contrast-enhanced
      micro-CT images. Three different accuracy metrics (Dice coefficient, organ volume
      recovery coefficient, and surface distance) were used for evaluation. The Dice
      coefficients vary from 0.45 +/- 0.18 for the spleen to 0.90 +/- 0.02 for the
      lungs, the volume recovery coefficients vary from 0.96 +/- 0.10 for the liver to
      1.30 +/- 0.75 for the spleen, the surface distances vary from 0.18 +/- 0.01 mm
      for the lungs to 0.72 +/- 0.42 mm for the spleen. The registration accuracy of
      the statistical atlas was compared with two publicly available single-subject
      mouse atlases, i.e., the MOBY phantom and the DIGIMOUSE atlas, and the results
      proved that the statistical atlas is more accurate than the single atlases. To
      evaluate the influence of the training subject size, different numbers of
      training subjects were used for atlas construction and registration. The results
      showed an improvement of the registration accuracy when more training subjects
      were used for the atlas construction. The statistical atlas-based registration
      was also compared with the thin-plate spline based deformable registration,
      commonly used in mouse atlas registration. The results revealed that the
      statistical atlas has the advantage of improving the estimation of low-contrast
      organs.

PMID- 21859616
TI  - Bag-of-features based medical image retrieval via multiple assignment and visual
      words weighting.
AB  - Bag-of-features based approaches have become prominent for image retrieval and
      image classification tasks in the past decade. Such methods represent an image as
      a collection of local features, such as image patches and key points with scale
      invariant feature transform (SIFT) descriptors. To improve the bag-of-features
      methods, we first model the assignments of local descriptors as contribution
      functions, and then propose a novel multiple assignment strategy. Assuming the
      local features can be reconstructed by their neighboring visual words in a
      vocabulary, reconstruction weights can be solved by quadratic programming. The
      weights are then used to build contribution functions, resulting in a novel
      assignment method, called quadratic programming (QP) assignment. We further
      propose a novel visual word weighting method. The discriminative power of each
      visual word is analyzed by the sub-similarity function in the bin that
      corresponds to the visual word. Each sub-similarity function is then treated as a
      weak classifier. A strong classifier is learned by boosting methods that combine
      those weak classifiers. The weighting factors of the visual words are learned
      accordingly. We evaluate the proposed methods on medical image retrieval tasks.
      The methods are tested on three well-known data sets, i.e., the ImageCLEFmed data
      set, the 304 CT Set, and the basal-cell carcinoma image set. Experimental results
      demonstrate that the proposed QP assignment outperforms the traditional nearest
      neighbor assignment, the multiple assignment, and the soft assignment, whereas
      the proposed boosting based weighting strategy outperforms the state-of-the-art
      weighting methods, such as the term frequency weights and the term frequency
      inverse document frequency weights.

PMID- 21859617
TI  - Analysis of fixed-point and coordinate descent algorithms for regularized kernel
      methods.
AB  - In this paper, we analyze the convergence of two general classes of optimization
      algorithms for regularized kernel methods with convex loss function and quadratic
      norm regularization. The first methodology is a new class of algorithms based on
      fixed-point iterations that are well-suited for a parallel implementation and can
      be used with any convex loss function. The second methodology is based on
      coordinate descent, and generalizes some techniques previously proposed for
      linear support vector machines. It exploits the structure of additively separable
      loss functions to compute solutions of line searches in closed form. The two
      methodologies are both very easy to implement. In this paper, we also show how to
      remove non-differentiability of the objective functional by exactly reformulating
      a convex regularization problem as an unconstrained differentiable stabilization
      problem.

PMID- 21859618
TI  - Two-dimensional approach to full-reference image quality assessment based on
      positional structural information.
AB  - A method for full-reference visual quality assessment based on the 2-D
      combination of two diverse metrics is described. The first metric is a measure of
      structural information loss based on the Fisher information about the position of
      the structures in the observed images. The second metric acts as a categorical
      indicator of the type of distortion that images underwent. These two metrics
      constitute the inner state of a virtual cognitive model, viewed as a system whose
      output is the automatic visual quality estimate. The use of a 2-D metric fills
      the intrinsic incompleteness of methods based on a single metric while providing
      consistent response across different image impairment factors and blind
      distortion classification capability with a modest computational overhead. The
      high accuracy and robustness of the method are demonstrated through cross
      validation experiments.

PMID- 21859619
TI  - Eye-tracking database for a set of standard video sequences.
AB  - This correspondence describes a publicly available database of eye-tracking data,
      collected on a set of standard video sequences that are frequently used in video
      compression, processing, and transmission simulations. A unique feature of this
      database is that it contains eye-tracking data for both the first and second
      viewings of the sequence. We have made available the uncompressed video sequences
      and the raw eye-tracking data for each sequence, along with different
      visualizations of the data and a preliminary analysis based on two well-known
      visual attention models.

PMID- 21859620
TI  - Tensor learning for regression.
AB  - In this paper, we exploit the advantages of tensorial representations and propose
      several tensor learning models for regression. The model is based on the
      canonical/parallel-factor decomposition of tensors of multiple modes and allows
      the simultaneous projections of an input tensor to more than one direction along
      each mode. Two empirical risk functions are studied, namely, the square loss and
      epsilon -insensitive loss functions. The former leads to higher rank tensor ridge
      regression (TRR), and the latter leads to higher rank support tensor regression
      (STR), both formulated using the Frobenius norm for regularization. We also use
      the group-sparsity norm for regularization, favoring in that way the low rank
      decomposition of the tensorial weight. In that way, we achieve the automatic
      selection of the rank during the learning process and obtain the optimal-rank TRR
      and STR. Experiments conducted for the problems of head-pose, human-age, and 3-D
      body-pose estimations using real data from publicly available databases, verified
      not only the superiority of tensors over their vector counterparts but also the
      efficiency of the proposed algorithms.

PMID- 21859622
TI  - Kronecker compressive sensing.
AB  - Compressive sensing (CS) is an emerging approach for the acquisition of signals
      having a sparse or compressible representation in some basis. While the CS
      literature has mostly focused on problems involving 1-D signals and 2-D images,
      many important applications involve multidimensional signals; the construction of
      sparsifying bases and measurement systems for such signals is complicated by
      their higher dimensionality. In this paper, we propose the use of Kronecker
      product matrices in CS for two purposes. First, such matrices can act as
      sparsifying bases that jointly model the structure present in all of the signal
      dimensions. Second, such matrices can represent the measurement protocols used in
      distributed settings. Our formulation enables the derivation of analytical bounds
      for the sparse approximation of multidimensional signals and CS recovery
      performance, as well as a means of evaluating novel distributed measurement
      schemes.

PMID- 21859621
TI  - Multiscale semilocal interpolation with antialiasing.
AB  - Aliasing is a common artifact in low-resolution (LR) images generated by a
      downsampling process. Recovering the original high-resolution image from its LR
      counterpart while at the same time removing the aliasing artifacts is a
      challenging image interpolation problem. Since a natural image normally contains
      redundant similar patches, the values of missing pixels can be available at
      texture-relevant LR pixels. Based on this, we propose an iterative multiscale
      semilocal interpolation method that can effectively address the aliasing problem.
      The proposed method estimates each missing pixel from a set of texture-relevant
      semilocal LR pixels with the texture similarity iteratively measured from a
      sequence of patches of varying sizes. Specifically, in each iteration, top
      texture-relevant LR pixels are used to construct a data fidelity term in a
      maximum a posteriori estimation, and a bilateral total variation is used as the
      regularization term. Experimental results compared with existing interpolation
      methods demonstrate that our method can not only substantially alleviate the
      aliasing problem but also produce better results across a wide range of scenes
      both in terms of quantitative evaluation and subjective visual quality.

PMID- 21859623
TI  - A semitransparency-based optical-flow method with a point trajectory model for
      particle-like video.
AB  - This paper proposes a new semitransparency-based optical-flow model with a point
      trajectory (PT) model for particle-like video. Previous optical-flow models have
      used ranging from image brightness constancy to image brightness change models as
      constraints. However, two important issues remain unsolved. The first is how to
      track/match a semitransparent object with a very large displacement between
      frames. Such moving objects with different shapes and sizes in an outdoor scene
      move against a complicated background. Second, due to semitransparency, the image
      intensity between frames can also violate a previous image brightness-based
      optical-flow model. Thus, we propose a two-step optimization for the optical-flow
      estimation model for a moving semitransparent object, i.e., particle. In the
      first step, a rough optical flow between particles is estimated by a new alpha
      constancy constraint that is based on an image generation model of
      semitransparency. In the second step, the optical flow of a particle with a
      continuous trajectory in a definite temporal interval based on a PT model can be
      refined. Many experiments using various falling-snow and foggy scenes with
      multiple moving vehicles show the significant improvement of the optical flow
      compared with a previous optical-flow model.

PMID- 21859624
TI  - Color constancy for multiple light sources.
AB  - Color constancy algorithms are generally based on the simplifying assumption that
      the spectral distribution of a light source is uniform across scenes. However, in
      reality, this assumption is often violated due to the presence of multiple light
      sources. In this paper, we will address more realistic scenarios where the
      uniform light-source assumption is too restrictive. First, a methodology is
      proposed to extend existing algorithms by applying color constancy locally to
      image patches, rather than globally to the entire image. After local (patch
      based) illuminant estimation, these estimates are combined into more robust
      estimations, and a local correction is applied based on a modified diagonal
      model. Quantitative and qualitative experiments on spectral and real images show
      that the proposed methodology reduces the influence of two light sources
      simultaneously present in one scene. If the chromatic difference between these
      two illuminants is more than 1 degrees , the proposed framework outperforms
      algorithms based on the uniform light-source assumption (with error-reduction up
      to approximately 30%). Otherwise, when the chromatic difference is less than 1
      degrees  and the scene can be considered to contain one (approximately) uniform
      light source, the performance of the proposed method framework is similar to
      global color constancy methods.

PMID- 21859625
TI  - Spatially optimized data-level fusion of texture and shape for face recognition.
AB  - Data-level fusion is believed to have the potential for enhancing human face
      recognition. However, due to a number of challenges, current techniques have
      failed to achieve its full potential. We propose spatially optimized data/pixel
      level fusion of 3-D shape and texture for face recognition. Fusion functions are
      objectively optimized to model expression and illumination variations in linear
      subspaces for invariant face recognition. Parameters of adjacent functions are
      constrained to smoothly vary for effective numerical regularization. In addition
      to spatial optimization, multiple nonlinear fusion models are combined to enhance
      their learning capabilities. Experiments on the FRGC v2 data set show that
      spatial optimization, higher order fusion functions, and the combination of
      multiple such functions systematically improve performance, which is, for the
      first time, higher than score-level fusion in a similar experimental setup.

PMID- 21859626
TI  - Wavelet variance analysis for random fields on a regular lattice.
AB  - There has been considerable recent interest in using wavelets to analyze time
      series and images that can be regarded as realizations of certain 1-D and 2-D
      stochastic processes on a regular lattice. Wavelets give rise to the concept of
      the wavelet variance (or wavelet power spectrum), which decomposes the variance
      of a stochastic process on a scale-by-scale basis. The wavelet variance has been
      applied to a variety of time series, and a statistical theory for estimators of
      this variance has been developed. While there have been applications of the
      wavelet variance in the 2-D context (in particular, in works by Unser in 1995 on
      wavelet-based texture analysis for images and by Lark and Webster in 2004 on
      analysis of soil properties), a formal statistical theory for such analysis has
      been lacking. In this paper, we develop the statistical theory by generalizing
      and extending some of the approaches developed for time series, thus leading to a
      large-sample theory for estimators of 2-D wavelet variances. We apply our theory
      to simulated data from Gaussian random fields with exponential covariances and
      from fractional Brownian surfaces. We demonstrate that the wavelet variance is
      potentially useful for texture discrimination. We also use our methodology to
      analyze images of four types of clouds observed over the southeast Pacific Ocean.

PMID- 21859627
TI  - Radial basis function networks with linear interval regression weights for
      symbolic interval data.
AB  - This paper introduces a new structure of radial basis function networks (RBFNs)
      that can successfully model symbolic interval-valued data. In the proposed
      structure, to handle symbolic interval data, the Gaussian functions required in
      the RBFNs are modified to consider interval distance measure, and the synaptic
      weights of the RBFNs are replaced by linear interval regression weights. In the
      linear interval regression weights, the lower and upper bounds of the interval
      valued data as well as the center and range of the interval-valued data are
      considered. In addition, in the proposed approach, two stages of learning
      mechanisms are proposed. In stage 1, an initial structure (i.e., the number of
      hidden nodes and the adjustable parameters of radial basis functions) of the
      proposed structure is obtained by the interval competitive agglomeration
      clustering algorithm. In stage 2, a gradient-descent kind of learning algorithm
      is applied to fine-tune the parameters of the radial basis function and the
      coefficients of the linear interval regression weights. Various experiments are
      conducted, and the average behavior of the root mean square error and the square
      of the correlation coefficient in the framework of a Monte Carlo experiment are
      considered as the performance index. The results clearly show the effectiveness
      of the proposed structure.

PMID- 21859628
TI  - Evolutionary and principled search strategies for sensornet protocol
      optimization.
AB  - Interactions between multiple tunable protocol parameters and multiple
      performance metrics are generally complex and unknown; finding optimal solutions
      is generally difficult. However, protocol tuning can yield significant gains in
      energy efficiency and resource requirements, which is of particular importance
      for sensornet systems in which resource availability is severely restricted. We
      address this multi-objective optimization problem for two dissimilar routing
      protocols and by two distinct approaches. First, we apply factorial design and
      statistical model fitting methods to reject insignificant factors and locate
      regions of the problem space containing near-optimal solutions by principled
      search. Second, we apply the Strength Pareto Evolutionary Algorithm 2 and Two
      Archive evolutionary algorithms to explore the problem space, with each iteration
      potentially yielding solutions of higher quality and diversity than the preceding
      iteration. Whereas a principled search methodology yields a generally applicable
      survey of the problem space and enables performance prediction, the evolutionary
      approach yields viable solutions of higher quality and at lower experimental
      cost. This is the first study in which sensornet protocol optimization has been
      explicitly formulated as a multi-objective problem and solved with state-of-the
      art multi-objective evolutionary algorithms.

PMID- 21859629
TI  - Detection and analysis of transitional activity in manifold space.
AB  - Activity monitoring is important for assessing daily living conditions for
      elderly patients and those with chronic diseases. Transitions between activities
      can present characteristic patterns that may be indicative of quality of
      movement. To detect and analyze transitional activities, a manifold-based
      approach is proposed in this paper. The proposed method uses a recursive spectral
      graph-partitioning algorithm to segment transitions in activity. These segments
      are subsequently mapped to a reference manifold space. Categorization of
      transitions is performed with the corresponding features in the manifold space.
      The practical value of the work is demonstrated through data collected under
      laboratory conditions, as well as patients recovering from total knee replacement
      operations, demonstrating specific transitions and motion impairment compared to
      normal subjects.

PMID- 21859630
TI  - Multiparametric decision support system for the prediction of oral cancer
      reoccurrence.
AB  - Oral squamous cell carcinoma (OSCC) constitutes the predominant neoplasm of the
      head and neck region, featuring particularly aggressive nature, associated with
      quite unfavorable prognosis. In this work we formulate a Decision Support System
      (DSS) which integrates a multitude of heterogeneous data (clinical, imaging and
      genomic), thus, framing all manifestations of the disease. Our primary aim is to
      identify the factors that dictate OSCC progression and subsequently predict
      potential relapses (local or metastatic) of the disease. The discrimination
      potential of each source of data is initially explored separately, and afterwards
      the individual predictions are combined to yield a consensus decision achieving
      complete discrimination between patients with and without a disease relapse. 

PMID- 21859631
TI  - Design and performance of a multichannel vestibular prosthesis that restores
      semicircular canal sensation in rhesus monkey.
AB  - In normal individuals, the vestibular labyrinths sense head movement and mediate
      reflexes that maintain stable gaze and posture. Bilateral loss of vestibular
      sensation causes chronic disequilibrium, oscillopsia, and postural instability.
      We describe a new multichannel vestibular prosthesis (MVP) intended to restore
      modulation of vestibular nerve activity with head rotation. The device comprises
      motion sensors to measure rotation and gravitoinertial acceleration, a
      microcontroller to calculate pulse timing, and stimulator units that deliver
      constant-current pulses to microelectrodes implanted in the labyrinth. This new
      MVP incorporates many improvements over previous prototypes, including a 50%
      decrease in implant size, a 50% decrease in power consumption, a new
      microelectrode array design meant to simplify implantation and reliably achieve
      selective nerve-electrode coupling, multiple current sources conferring ability
      to simultaneously stimulate on multiple electrodes, and circuitry for in vivo
      measurement of electrode impedances. We demonstrate the performance of this
      device through in vitro bench-top characterization and in vivo physiological
      experiments with a rhesus macaque monkey.

PMID- 21859632
TI  - High-frequency stimulation selectively blocks different types of fibers in frog
      sciatic nerve.
AB  - Conduction block using high-frequency alternating current (HFAC) stimulation has
      been shown to reversibly block conduction through various nerves. However, unlike
      simulations and experiments on myelinated fibers, prior experimental work in our
      lab on the sea-slug, Aplysia, found a nonmonotonic relationship between frequency
      and blocking thresholds in the unmyelinated fibers. To resolve this discrepancy,
      we investigated the effect of HFAC waveforms on the compound action potential of
      the sciatic nerve of frogs. Maximal stimulation of the nerve produces a compound
      action potential consisting of the A-fiber and C-fiber components corresponding
      to the myelinated and unmyelinated fibers' response. In our study, HFAC waveforms
      were found to induce reversible block in the A-fibers and C-fibers for
      frequencies in the range of 5-50 kHz and for amplitudes from 0.1-1 mA. Although
      the A-fibers demonstrated the monotonically increasing threshold behavior
      observed in published literature, the C-fibers displayed a nonmonotonic
      relationship, analogous to that observed in the unmyelinated fibers of Aplysia.
      This differential blocking behavior observed in myelinated and unmyelinated
      fibers during application of HFAC waveforms has diverse implications for the
      fields of selective stimulation and pain management.

PMID- 21859633
TI  - Mammalian muscle model for predicting force and energetics during physiological
      behaviors.
AB  - Muscles convert metabolic energy into mechanical work. A computational model of
      muscle would ideally compute both effects efficiently for the entire range of
      muscle activation and kinematic conditions (force and length). We have extended
      the original Virtual Muscle algorithm (Cheng , 2000) to predict energy
      consumption for both slow- and fast-twitch muscle fiber types, partitioned
      according to the activation process   (E(a)), cross-bridge cycling  (E(xb)) and
      ATP/PCr recovery  (E(recovery)). Because the terms of these functions correspond
      to identifiable physiological processes, their coefficients can be estimated
      directly from the types of experiments that are usually performed and
      extrapolated to dynamic conditions of natural motor behaviors. We also
      implemented a new approach to lumped modeling of the gradually recruited and
      frequency modulated motor units comprising each fiber type, which greatly reduced
      computational time. The emergent behavior of the model has significant
      implications for studies of optimal motor control and development of
      rehabilitation strategies because its trends were quite different from
      traditional estimates of energy (e.g., activation, force, stress, work, etc.).
      The model system was scaled to represent three different human experimental
      paradigms in which muscle heat was measured during voluntary exercise; predicted
      and observed energy rate agreed well both qualitatively and quantitatively.

PMID- 21859634
TI  - Neural feedback for instantaneous spatiotemporal modulation of afferent pathways
      in bi-directional brain-machine interfaces.
AB  - In bi-directional brain-machine interfaces (BMIs), precisely controlling the
      delivery of microstimulation, both in space and in time, is critical to
      continuously modulate the neural activity patterns that carry information about
      the state of the brain-actuated device to sensory areas in the brain. In this
      paper, we investigate the use of neural feedback to control the spatiotemporal
      firing patterns of neural ensembles in a model of the thalamocortical pathway.
      Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is
      achieved based on microstimulation of thalamic relay cells through multiple-input
      multiple-output (MIMO) feedback controllers. This closed loop feedback control
      mechanism is achieved by simultaneously varying the stimulation parameters across
      multiple stimulation electrodes in the thalamic circuit based on continuous
      monitoring of the difference between reference patterns and the evoked responses
      of the cortical PY cells. We demonstrate that it is feasible to achieve a desired
      level of performance by controlling the firing activity pattern of a few "key"
      neural elements in the network. Our results suggest that neural feedback could be
      an effective method to facilitate the delivery of information to the cortex to
      substitute lost sensory inputs in cortically controlled BMIs.

PMID- 21859635
TI  - Towards design of a stumble detection system for artificial legs.
AB  - Recent advances in design of powered artificial legs have led to increased
      potential to allow lower limb amputees to actively recover from stumbles. To
      achieve this goal, promptly and accurately identifying stumbles is essential.
      This study aimed to 1) select potential stumble detection data sources that react
      reliably and quickly to stumbles and can be measured from a prosthesis, and 2)
      investigate two different approaches based on selected data sources to detect
      stumbles and classify stumble types in patients with transfemoral (TF)
      amputations during ambulation. In the experiments, the normal gait of TF amputees
      was perturbed by a controllable treadmill or when they walked on an obstacle
      course. The results showed that the acceleration of prosthetic foot can
      accurately detect the tested stumbling events 140-240 ms before the critical
      timing of falling and precisely classify the stumble type. However, the detector
      based on foot acceleration produced high false alarm rates, which challenged its
      real application. Combining electromyographic (EMG) signals recorded from the
      residual limb with the foot acceleration significantly reduced the false alarm
      rate but sacrificed the detection response time. The results of this study may
      lead to design of a stumble detection system for instrumented, powered artificial
      legs; however, continued engineering efforts are required to improve the
      detection performance and resolve the challenges that remain for implementing the
      stumble detector on prosthetic legs.

PMID- 21859637
TI  - Letter to the editor: concomitant off-pump coronary artery bypass grafting and
      thymectomy.

PMID- 21859636
TI  - Benzene metabolite 1,2,4-benzenetriol induces halogenated DNA and tyrosines
      representing halogenative stress in the HL-60 human myeloid cell line.
AB  - BACKGROUND: Although benzene is known to be myelotoxic and to cause myeloid
      leukemia in humans, the mechanism has not been elucidated. OBJECTIVES: We focused
      on 1,2,4-benzenetriol (BT), a benzene metabolite that generates reactive oxygen
      species (ROS) by autoxidation, to investigate the toxicity of benzene leading to
      leukemogenesis. METHODS: After exposing HL-60 human myeloid cells to BT, we
      investigated the cellular effects, including apoptosis, ROS generation, DNA
      damage, and protein damage. We also investigated how the cellular effects of BT
      were modified by hydrogen peroxide (H2O2) scavenger catalase, hypochlorous acid
      (HOCl) scavenger methionine, and 4-aminobenzoic acid hydrazide (ABAH), a
      myeloperoxidase (MPO)-specific inhibitor. RESULTS: BT increased the levels of
      apoptosis and ROS, including superoxide (O2*-), H2O2, HOCl, and the hydroxyl
      radical (*OH). Catalase, ABAH, and methionine each inhibited the increased
      apoptosis caused by BT, and catalase and ABAH inhibited increases in HOCl and
      *OH. Although BT exposure increased halogenated DNA, this increase was inhibited
      by catalase, methionine, and ABAH. BT exposure also increased the amount of
      halogenated tyrosines; however, it did not increase 8-oxo-deoxyguanosine.
      CONCLUSIONS: We suggest that BT increases H2O2 intracellularly; this H2O2 is
      metabolized to HOCl by MPO, and this HOCl results in possibly cytotoxic binding
      of chlorine to DNA. Because myeloid cells copiously express MPO and because
      halogenated DNA may induce both genetic and epigenetic changes that contribute to
      carcinogenesis, halogenative stress may account for benzene-induced bone marrow
      disorders and myeloid leukemia.

PMID- 21859638
TI  - The impact of non-dialysis-dependent renal dysfunction on outcome following
      cardiac surgery.
AB  - BACKGROUND: We evaluated the results of different types of cardiovascular surgery
      in patients with chronic renal failure (CRF) (serum creatinine >=2 mg/dL) who
      were not dialysis-dependent. METHODS: Eighty-two patients who presented with non
      dialysis-dependent CRF were retrospectively evaluated. Patients in Group 1 (n =
      12) underwent valvular surgery, those in Group 2 (n = 58) underwent coronary
      artery bypass grafting (CABG), and those in Group 3 (n = 12) underwent combined
      CABG and valvular surgery. RESULTS: The demographics were similar among the
      groups. Cardiopulmonary bypass and aortic cross-clamping times were shorter (P <
      .01), the use of blood and blood products was less, and the mechanical
      ventilation time and hospital stay were shorter in Group 2 in comparison to the
      other groups (P < .01). There were 4 (6.9%) early mortalities in Group 2. Late
      mortalities occurred in 4 (33.3%), 16 (27.6%), and 6 (50%) patients from Groups
      1, 2, and 3, respectively. Cox regression analysis revealed that age, the
      presence of a preoperative cerebrovascular accident, the presence of a left main
      coronary lesion, preoperative blood urea nitrogen level, and the use of blood and
      blood products were independent risk factors for early mortality. High Euroscore,
      cerebrovascular accident, the use of platelet suspension, longer ventilation
      support times, and combined CABG and valvular surgery were independent risk
      factors for late mortality. CONCLUSIONS: Morbidity and survival seemed to be more
      dependent on preoperative patient characteristics than the type of surgery in
      this group of patients. Combined CABG and valvular surgery was a risk factor for
      late mortality.

PMID- 21859639
TI  - Impact of race on mitral procedure selection and short-term outcomes of patients
      undergoing mitral valve surgery.
AB  - BACKGROUND: Racial disparity with respect to mitral valve (MV) surgery has been
      documented; however, previous reports have been limited by small numbers, focus
      on patients undergoing MV replacement only, or comparison of African-American
      patients to white patients. Using more recent data from the largest all-payer
      database in the United States, we examined whether type of mitral procedure
      performed was influenced by race and whether racial differences exist in baseline
      characteristics and short-term outcomes of patients undergoing mitral repair or
      replacement for MV disease. METHODS: Using the 2005-2007 National Inpatient
      Sample (NIS) Database, we identified patients >= 30 years of age who underwent MV
      repair or replacement, excluding ischemic and congenital MV disease. Patients
      were stratified into 4 racial groups: whites, African-Americans, Hispanics, and
      others. The 4 groups were compared with respect to baseline characteristics, type
      of MV procedure (repair versus replacement), and short-term outcomes. RESULTS:
      Non-whites comprised 22.3% (7818 out of 35,074) of the patients and were
      generally younger, more often on Medicaid and from urban locations, and more
      often presented on an urgent/emergent basis. African-Americans and Hispanics
      tended to be less affluent and have a higher Charlson comorbidity index. MV
      repair was performed in 45.8% of the patients overall. The racial groups differed
      significantly with respect to the proportion of patients receiving repair.
      Hispanics were 2 times more likely to have MV replacement compared to whites
      (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.52-2.80, P = .0001),
      and African-Americans were more than 1.5 times more likely to have replacement
      compared to whites (OR = 1.69, 95% CI = 1.35-2.11). Following adjustment for
      baseline characteristics, there was no difference with respect to race for in
      hospital mortality or likelihood of repair, but differences between groups
      persisted for length of stay and discharge location. African-Americans and
      Hispanics were more likely than whites to have a prolonged hospitalization.
      CONCLUSIONS: African-Americans and Hispanics present for MV surgery with worse
      preoperative profiles and undergo mitral repair less often compared to whites.
      Although in-hospital mortality was not influenced by race, African-Americans and
      Hispanics had a more protracted hospital course even following adjustment. The
      disparity in mitral procedure selection among racial groups was present only
      prior to adjustment for important baseline characteristics. Nevertheless, this
      racial difference reflects current reality in surgical practice and identifies an
      important area for future improvement in the care of patients with valvular heart
      disease.

PMID- 21859640
TI  - Effects of high-dose mucosolvin on lung functions in infant patients with
      cardiopulmonary bypass.
AB  - BACKGROUND: Cardiopulmonary bypass may cause serious impairment of lung function.
      It has been reported that administration of mucosolvin can prevent acute
      respiratory insufficiency through the improvement of pulmonary surfactant.
      OBJECTIVES: This study aimed to explore the effects of high-dose mucosolvin on
      infant lungs following cardiopulmonary bypass. METHODS: One hundred infants were
      randomly divided into 2 groups. In Group 1, patients did not receive any
      respiratory drug perioperatively and underwent conventional mechanical
      ventilation postoperatively. In Group 2, patients were administered mucosolvin
      (15 mg/kg per day) perioperatively, and doxofylline (15 mg/kg per day) and
      ipratropium bromide solution (200 MUg) were administrated postoperatively.
      Mechanical ventilation parameters, pulmonary surfactant-related protein (SP-B),
      and cytokines were evaluated after induction of anesthesia and 30 minutes, 24
      hours, and 48 hours after CPB. RESULTS: At the end of CPB, all PaO2/FiO2 values
      in Group 2 were higher than those in Group 1. Postoperative SP-B levels in Group
      1 decreased significantly compared to the baseline value (P < .05). There was no
      significant difference in hospitalization time between both groups, but both
      mechanical ventilation time and intensive care unit time of infants in Group 2
      were significantly shorter than those in group 1 (P < .05). CONCLUSIONS: These
      findings indicate that high-dose mucosolvin has certain protective effects on
      respiratory functions in infants undergoing heart operations with CPB and that it
      that has no adverse effects.

PMID- 21859641
TI  - Minimally invasive transaortic repair of the mitral valve.
AB  - OBJECTIVE: We retrospectively evaluated the results of an edge-to-edge repair
      (Alfieri stitch) of the mitral valve performed via a transaortic approach in
      patients who were undergoing minimally invasive aortic valve replacement.
      METHODS: From January 2010 to September 2010, 6 patients underwent minimally
      invasive edge-to-edge repair of the mitral valve via a transaortic approach with
      concomitant aortic valve replacement. The patients were considered to be
      candidates for this procedure if they were deemed by the surgeon to be high-risk
      for a double valve procedure and if on preoperative transesophageal
      echocardiogram the mitral regurgitation jet originated from the middle portion
      (A2/P2 segments) of the mitral valve. RESULTS: There was no operative mortality.
      Mean cardiopulmonary bypass time was 137 minutes, and mean cross-clamp time was
      111 minutes. There was a significant improvement in the mean mitral regurgitation
      grade, with a mean of 3.8 preoperatively and 0.8 postoperatively. The ejection
      fraction remained stable, with mean preoperative and postoperative ejection
      fractions of 43.3% and 47.5%, respectively. Follow-up transthoracic
      echocardiograms obtained at a mean of 33 days postoperatively (range, 8-108 days)
      showed no significant worsening of mitral regurgitation. CONCLUSION: Transaortic
      repair of the mitral valve is feasible in patients undergoing minimally invasive
      aortic valve replacement.

PMID- 21859642
TI  - Pulmonary homografts for aortic valve replacement: long-term comparison with
      aortic grafts.
AB  - OBJECTIVE: The use of homografts for aortic valve replacement (AVR) is an
      alternative to mechanical or biological valve prostheses, especially in younger
      patients. This retrospective comparative study evaluated our single-center long
      term results, with a focus on the different origins of the homografts. METHODS:
      Since 1992, 366 adult patients have undergone AVR with homografts at our center.
      We compared 320 homografts of aortic origin and 46 homografts of pulmonary
      origin. The grafts were implanted via either a subcoronary technique or the root
      replacement technique. We performed a multivariate analysis to identify
      independent factors that influence survival. Freedom from reintervention and
      survival rates were calculated as cumulative events according to the Kaplan-Meier
      method, and differences were tested with the log-rank test. RESULTS: Overall
      mortality within 1 year was 6.5% (21/320) in the aortic graft group and 17.4%
      (8/46) in the pulmonary graft group. In the pulmonary graft group, 4 patients
      died from valve-related complications, 1 patient died after additional
      heterotopic heart transplantation, and 1 patient who entered with a primary
      higher risk died from a prosthesis infection. Two patients died from non-valve
      related causes. During the long-term follow-up, the 15-year survival rate was
      79.9% for patients in the aortic graft group and 68.7% for patients in the
      pulmonary graft group (P = .049). The rate of freedom from reoperation was 77.7%
      in the aortic graft group and 57.4% in the pulmonary graft group (P < .001). The
      reasons for homograft explantation were graft infections (aortic graft group,
      5.0%; pulmonary graft group, 6.5%) and degeneration (aortic graft group, 7.5%;
      pulmonary graft group, 32.6%). CONCLUSION: Our study demonstrated superior rates
      of survival and freedom from reintervention after AVR with aortic homografts.
      Implantation with a pulmonary graft was associated with a higher risk of redo
      surgery, owing to earlier degenerative alterations.

PMID- 21859643
TI  - Radical and harmless shave resection of atypical papillary fibroelastomas of the
      cardiac valves.
AB  - BACKGROUND: Papillary fibroelastomas (PFEs) are rare cardiac tumors usually
      treated by shave resection. Up to 20% of the patients are actually denied such a
      conservative surgical approach because atypical morphology is thought to preclude
      radical and effective outcomes. METHODS/RESULTS: Surgical tricks and tips of
      shave resection are elucidated, and a case series presentation of the morphology
      of atypical PFEs treated by shave resection is described. CONCLUSION: In
      experienced hands surgical shave resection is the gold standard for the treatment
      of PFE even in atypical presentations.

PMID- 21859644
TI  - Unique case of primary malignant fibrous histiocytoma of the right ventricle with
      moderator band involvement.
AB  - Malignant primary tumors of the heart are very rare and in most cases are located
      in the left side of the heart, but involvement of the moderator band of the right
      heart has not yet been described in the literature. We report the case of a 22
      year-old woman who presented after an episode of transient sudden loss of
      consciousness. The transthoracic echocardiography (TTE) and transesophageal
      echocardiography evaluations showed an echogenic mass that originated in the
      right ventricle and protruded into the tricuspid valve during systole. While
      operating on the patient, we found a sessile tumor that originated exclusively
      from the moderator band of the right ventricle. The tumor was completely resected
      through the tricuspid valve. An immunohistochemistry examination of the tumor
      confirmed the diagnosis of a malignant fibrous histiocytoma (MFH)
      (undifferentiated pleomorphic sarcoma). To our knowledge, this case is the first
      of moderator band involvement among the 50 cases of primary MFH of the heart that
      have been reported in the literature. After a year and a half, TTE, computed
      tomography (CT), and positron emission tomography CT (PET-CT) showed the absence
      of cardiac tumor, a normal tricuspid function, and no metastasis. The
      completeness of the surgical resection and the absence of local recurrence >1
      year after surgery are encouraging signs for the patient's outcome.

PMID- 21859645
TI  - Aortoesophageal fistula secondary to thoracic endovascular aortic repair of a
      descending aortic aneurysm rupture.
AB  - PURPOSE: We present the case of a patient who developed an aortoesophageal
      fistula (AEF) 4 years after thoracic endovascular aortic repair (TEVAR) of a
      descending thoracic aortic aneurysm rupture. CASE REPORT: A 60-year-old female
      patient underwent emergency stent graft placement in December 2006 because of
      rupture of a distal descending aortic aneurysm. The patient was discharged
      uneventfully. Four years later, the patient was readmitted because of recurrent
      hematemesis, weight loss, and malaise. A computed tomography scan and an upper
      gastrointestinal system (GIS) endoscopy examination revealed an AEF located at
      the midportion of the esophagus and at the caudal end of the stent graft. An
      emergency stent graft was re-replaced into the previous graft. The patient died
      from hemorrhagic shock due to massive GIS bleeding while she was being prepared
      for secondary major esophageal surgery. CONCLUSION: AEF is a catastrophic
      complication of TEVAR. Conservative treatment is often associated with fatal
      results. If possible, these patients should be treated with secondary major
      surgical procedures.

PMID- 21859646
TI  - Coincidence of free-floating thrombus in the aortic arch, severe mitral stenosis,
      and left atrial appendage clot.
AB  - We describe the surgical management of a free-floating thrombus in the aortic
      arch in a patient with severe mitral stenosis, a left atrial appendage (LAA)
      clot, and an iliac artery thrombus. A 60-year-old woman complaining of dyspnea
      and pain in her right leg was referred to our multidisciplinary clinic. After a
      brief history was taken, an electrocardiography evaluation showed atrial
      fibrillation. Color Doppler sonography of the lower limb arteries showed
      decreased blood flow in distal branches of the internal iliac artery of the right
      leg. Transthoracic and transesophageal echocardiography evaluations revealed
      severe mitral stenosis, a large LAA clot, and a large mobile mass (2 * 1.5 * 1.5
      cm) in the distal aortic arch. Additional investigations with computed
      tomographic angiography revealed that the thrombus extended from the aortic arch
      to the subclavian artery. Another bulky thrombus in the right iliac artery was
      also found. Given this complicated medical situation, emergency cardiac surgery
      was performed, and the clot was removed. The stenotic mitral valve was replaced
      with a prosthetic valve, The LAA was closed after clot removal, and the bulky
      thrombus was extracted from the right iliac artery. Transesophageal
      echocardiographic data were obtained postoperatively, and the patient's course in
      the intensive care unit was favorable. She was discharged from the hospital in
      good condition on warfarin, digoxin, aspirin, and metoprolol.

PMID- 21859647
TI  - Congenital left main coronary artery to coronary sinus fistula.
AB  - Congenital coronary artery fistula is an extremely rare anomaly that may involve
      any of the coronary arteries and any of the cardiac chambers. We report the case
      of a 14-year-old female patient with a symptomatic congenital coronary fistula
      starting from the left main coronary artery and draining to the coronary sinus.
      The patient underwent surgical ligation of the fistula and had an excellent
      outcome.

PMID- 21859648
TI  - Surgical strategy for biventricular assist device implantation after previous
      coronary artery bypass grafting.
AB  - In an aging population, numerous patients who underwent previous coronary artery
      bypass grafting (CABG) are presenting with end-stage ischemic cardiomyopathy.
      Although redo CABG and cardiological interventions are possible treatment
      options, orthotopic heart transplantation remains an ultimate option for these
      patients. However, there is high morbidity and mortality on the waiting list, and
      mechanical circulatory support is a life-saving concept [Hetzer 2006; Taylor
      2009].We developed a simplified and safe technique for implantation of a
      biventricular assist device as a redo in complex patients after previous CABG and
      end-stage heart failure.

PMID- 21859649
TI  - The first case report of a metastatic myxoid liposarcoma invading the left atrial
      cavity and pulmonary vein.
AB  - Myxoid liposarcoma (MLS) is the most commonly encountered liposarcoma subgroup,
      accounting for about 50% of all cases. Metastatic MLS of the heart is extremely
      rare. Herein we describe for the first time metastasis of MLS to the left atrium
      and left upper pulmonary vein in a 54-year-old woman who was admitted with
      shortness of breath and cough persisting for 2 weeks. The patient reported that a
      total surgical excision of MLS of the left thigh followed by radiotherapy was
      performed 4 years ago. An emergency operation was performed due to rapidly
      progressive worsening of clinical condition and echocardiographic determination
      of left atrial mass protruding into the left ventricle and obstructing the mitral
      inflow throughout the diastole. The mass could not be totally excised because it
      was tightly adhered to the surrounding tissue. Postoperative magnetic resonance
      imaging (MRI) showed a 5 * 3 cm residual tumor deforming the posterior wall of
      the left atrium entirely and extending into the left upper pulmonary vein.
      Histopathological examination was consistent with MLS. In conclusion, considering
      probable cardiac metastasis in patients presenting with respiratory symptoms with
      medical history of soft tissue sarcomas would be life saving. The case is
      discussed, and a review of the literature in relation to the metastatic
      involvement of the heart by MLS is presented.

PMID- 21859650
TI  - Aortopulmonary window with subaortic fibrous stenosis and septal defect: surgery
      through a minimal right vertical infra-axillary thoracotomy.
AB  - Aortopulmonary window with subaortic stenosis and ventricular septal defect is an
      uncommon congenital cardiac malformation that is repaired using cardiopulmonary
      bypass. The authors describe a 3-year-old patient on whom we performed surgery
      through a minimal right vertical infra-axillary thoracotomy. This minimally
      invasive surgery is likely to be applicable in a few cases.

PMID- 21859651
TI  - Surgical repair of a giant atrial septal aneurysm with patent foramen ovale.
AB  - Atrial septal aneurysm (ASA) is a rare occurrence. Many studies have established
      a correlation between ASA and both ischemic stroke of unidentified cause and
      cardiac embolism. We describe the case of a 59-year-old woman who had a giant ASA
      with patent foramen ovale. The aneurysm was successfully removed. Although the
      detailed mechanism involved in the degeneration of the atrial septum is unclear,
      we recommend that such damage be surgically repaired to reduce the risk of
      cerebral embolism or heart failure in symptomatic patients. Surgery is
      recommended for larger ASA.

PMID- 21859652
TI  - Environmental pollution as a cause of papillary fibroelastoma: hints for a new
      etiological hypothesis?
AB  - BACKGROUND: Environmental pollution has adverse human health effects, mostly on
      the respiratory tract but also on the cardiovascular system. Papillary
      fibroelastomas are exceedingly rare primary cardiac tumors; their pathologic
      origin remains still elusive. CASE REPORT: This is a brief report on 3 patients
      referred for surgical treatment of papillary fibroelastomas in the last 6 months.
      All patients were born, lived, and worked in a narrow region in Campania that is
      under active monitoring because of high rates of environmental pollution.
      CONCLUSIONS: Known mechanisms of cardiovascular damage generated by environmental
      pollution are cross linked with described papillary fibroelastomas' etiological
      cascade. Evidence is suggested for a common origin. These results provide
      intriguing but inconclusive insights into pathophysiological pathways that may
      link exposure to environmental pollution and development of papillary
      fibroelastomas.

PMID- 21859653
TI  - Soyfoods, hyperuricemia and gout: a review of the epidemiologic and clinical
      data.
AB  - Soyfoods have long been a part of traditional Asian diets; they provide plentiful
      amounts of high-quality protein and have a favourable fatty acid profile. In
      addition, provocative research suggests soyfoods offer health benefits
      independent of the nutrients they provide. However, there is a widely-held belief
      among Asian health professionals and the public that soyfoods increase risk of
      gout and potentially precipitate acute attacks in patients with this disease. To
      examine the veracity of this belief, this review critically evaluated the
      relevant clinical and epidemiologic data. In addition, background information on
      the etiology and prevalence of hyperuricemia and gout in Asia is provided along
      with the results of a small survey of Asian healthcare professionals about their
      attitudes toward soyfoods. Among the healthcare professionals who responded to
      the survey, 95% considered soyfoods to be somewhat or very healthy and
      nutritious. In contrast, 48% expressed the view that soyfoods are likely to cause
      gout. However, none of the six epidemiologic studies identified provided any
      evidence that soy intake was associated with circulating uric acid levels,
      hyperuricemia or gout. Data from the five human intervention studies evaluated
      indicate soy protein does elevate serum uric levels, but in response to amounts
      comparable to Asian intake, the expected rise would almost certainly be
      clinically irrelevant. Although there is a need for long-term research, on the
      basis of the existing data there is no reason for individuals with gout or at
      risk of developing gout to avoid soyfoods.

PMID- 21859654
TI  - A situational review of infant and young child feeding practices and
      interventions in Viet Nam.
AB  - Sub-optimal infant and young child feeding (IYCF) practices are likely a
      significant contributor to high undernutrition rates in Viet Nam. To date,
      however, there has been no comprehensive review of IYCF practices in Viet Nam.
      The objectives of this paper were to review: 1) patterns/trends in IYCF in Viet
      Nam; 2) the barriers and facilitators to IYCF practices; and 3) interventions and
      policies and their effectiveness. Methods used include reviewing and analyzing
      existing data, summarizing and organizing the evidence into broad themes based on
      a pre-defined conceptual framework. Findings show that the proportion of children
      ever breastfed is almost universal and the median duration of breastfeeding is 13
      18 months. However, exclusive breastfeeding for the first six months is low (8
      17%) and appears to be declining over time. Information on complementary feeding
      is limited, but two key challenges are: early introduction, and low nutrient
      quality of complementary foods. Facilitators of optimal IYCF were support from 1)
      government progressive policies, 2) non-profit organizations and 3) family
      members. Barriers to optimal IYCF included 1) the lack of enforcement of, and
      compliance with the code of marketing breast milk substitutes, 2) inadequate
      knowledge among health care providers; and 3) maternal poor knowledge. These
      findings indicate that the evidence base on complementary feeding is weak in Viet
      Nam and needs to be strengthened. The review also reinforces that program and
      policy actions to improve IYCF in Viet Nam must target multiple stakeholders at
      different levels: the family, the health system and the private sector.

PMID- 21859655
TI  - Micronutrients decrease incidence of common infections in type 2 diabetic
      outpatients.
AB  - A randomized, double-blind, placebo-controlled trial was carried out to
      investigate the effects of micronutrients supplementation on immunity and the
      incidence of common infections in type 2 diabetic outpatients. A total of 196
      type 2 diabetic outpatients were randomized to receive tablets of micronutrients
      (n=97) or placebo (n=99) for 6 months. Individualized dietary energy intake and
      daily physical activity were recommended. Anthropometric measurements, blood
      biochemical variables and the incidence of common infections were measured at
      baseline and at 6 months. Data on diet, exercise and infection (upper respiratory
      tract infection, skin infection, urinary and genital tract infections, other
      infections) were recorded 1 month before the study and every month during the
      study. Blood concentrations of total protein, iron (Fe), folic acid and
      hemoglobin increased and unsaturated iron-binding capacity(UIBC) levels were
      decreased in the micronutrients supplementation group compared to the placebo
      group at 6 months. Moreover, at 6 months, compared to the placebo group, the
      blood concentrations of IgE, CD4+, CD4+/CD8+, WBC, lymphocyte counts, basophilic
      leukocyte increased and CD8+ count decreased in the supplementation group, and
      the levels of IgA, IgM, IgG and complements C3 and C4 did not differ. The
      incidence of upper respiratory infection, whitlow, dermapostasis, vaginitis,
      urinary tract infection, gingivitis and dental ulcer were lower and body
      temperature and duration of fever greatly improved in the supplementation than
      the placebo group. These data indicated that supplementation of micronutrients
      might increase immune function and reduce the incidence of common infections in
      type 2 diabetic outpatients.

PMID- 21859656
TI  - Effect of soy drink replacement in a weight reducing diet on anthropometric
      values and blood pressure among overweight and obese female youths.
AB  - BACKGROUND: Soy drink replacement in the diet might have beneficial effects on
      anthropometric and blood pressure values for overweight and obese subjects.
      Therefore, we are going to determine the effects of soy drink replacements on the
      weight, waist circumference and blood pressure among overweight and obese female
      youths. PATIENTS AND METHODS: This was a cross-over randomized clinical trial on
      23 overweight and obese female subjects. All patients were on a weight reducing
      diet. There were two trial periods for six weeks (soy drink period and cow's milk
      period) and a washout period for 3 weeks. In the soy drink period only one glass
      of soy drink (240 cc) was consumed instead of one glass of cow's milk. RESULTS:
      The mean age of the patients was 22+/-2 years. Mean of BMI was 28.1+/-0.5. Weight
      and waist circumference did not changed significantly after the soy drink period
      compared to the cow's milk period. Systolic blood pressure reduced significantly
      following the soy drink period (mean percent change in soy drink period: -4.0+/
      0.9 vs -1.7+/-0.5 in the cow's milk period; p<0.05). Diastolic blood pressure
      also reduced in the soy drink period (-0.4+/-0.1 vs 0.4+/-0.1; p<0.05).
      CONCLUSION: Soy drink replacement could reduce both systolic and diastolic blood
      pressure among overweight and obese female youths. However, this replacement had
      no significant results on weight and waist circumference.

PMID- 21859657
TI  - Examination of Chinese habitual dietary protein requirements of Chinese young
      female adults by indicator amino acid method.
AB  - OBJECTIVE: To determine protein requirement of Chinese young female adults on
      habitual Chinese diet through indicator amino acid oxidation (IAAO) technique.
      DESIGN: Twenty women with a mean (SD) age of 21.6 (0.9) years were healthy based
      on questionnaire, physical examinations and screening tests. There were three
      consecutive periods of 7 days each with six different intakes of protein (0.70,
      0.78, 0.86, 0.94, 1.02 and 1.10 g/kg.d) within Chinese habitual diets
      (proportions of good-quality protein were 40 to 45%). Subjects were randomly
      allocated equally into two groups (1.10, 0.86, 0.78 g/kg.d for group 1 and 1.02,
      0.94, 0.70 g/kg.d for group 2 from period 1 to period 3 in turn). Adaptation days
      were from day 1 to day 6 and the isotope study day was day 7 in each period.
      Amino acid kinetics was measured in non-menstrual periods, based on the IAAO
      technique. Two indicators (rate of release of 13CO2 and rate of leucine
      oxidation) were used to estimate protein requirement by breakpoint analysis with
      a two-phase linear regression crossover model. RESULTS: Mean and population safe
      protein requirements of Chinese habitual diets in non-menstrual periods from the
      rate of release of 13CO2 were 0.91 and 1.09 g/kg.d, respectively. And from the
      rate of leucine oxidation were 0.92 and 1.10 g/kg.d, respectively. CONCLUSIONS:
      The protein requirement of young women on Chinese habitual diets in non-menstrual
      period was lower than the current protein reference intake for Chinese females.
      Further studies are necessary to explore female protein requirements during the
      whole menstrual cycle.

PMID- 21859658
TI  - Prevalence of vitamin D insufficiency and risk factors for type 2 diabetes and
      cardiovascular disease among African migrant and refugee adults in Melbourne: a
      pilot study.
AB  - Migration to industrialised countries poses a "double whammy" for type 2 diabetes
      among sub-Saharan African migrant and refugee adults. This population group has
      been found to be at an increased risk of obesity and type 2 diabetes, which may
      be further aggravated by inadequate vitamin D status. Thus, this study aimed to
      describe the demographics of vitamin D insufficiency, obesity, and risk factors
      for type 2 diabetes among sub-Saharan African migrants and refugees aged 20 years
      or older living in Melbourne, Australia (n=49). Data were obtained by a
      questionnaire, medical assessment, and fasting blood samples. The mean serum 25
      hydroxyvitamin D level was 27.3 nmol/L (95% CI: 22.2, 32.4 nmol/L); with 25
      hydroxyvitamin D levels <50 nmol/L occurring in 88% of participants. Participants
      displayed a cluster of risk factors for type 2 diabetes and cardiovascular
      disease: 62% were overweight or obese, 47% had insulin resistance (HOMA-IR >=2),
      25% had low density lipoprotein cholesterol levels >=3.5 mmol/L, 24.5% had high
      density lipoprotein cholesterol levels <=1.03 mmol/L, 34.6% had borderline or
      high levels of total cholesterol (>=5.2 mmol/L), 18.2% had borderline or high
      levels of triglyceride (>=1.7 mmol/L), and 16% had hypertension (systolic blood
      pressure >=140 mmHg or diastolic blood pressure >=90 mmHg). These findings
      suggest that sub-Saharan African migrants and refugees may be at risk of type 2
      diabetes and atherosclerosis-related diseases such as ischemic heart disease,
      stroke, and peripheral vascular disease. Well-designed vitamin D interventions
      that incorporate lifestyle changes are urgently needed in this sub-population.

PMID- 21859659
TI  - Veganism does not reduce the risk of the metabolic syndrome in a Taiwanese
      cohort.
AB  - The purpose of the present study was to assess the risk of the metabolic syndrome
      (MS) with vegan, pescovegetarian, lactovegetarian and nonvegetarian diets in
      Taiwan. The design was a retrospective cohort study using secondary data analysis
      from a Taiwan longitudinal health check-up database provided by MJ Health
      Screening Center during 1996-2006. A total of 93209 participants were classified
      as vegans (n=1116), pescovegetarians (n=2461), lactovegetarians (n=4313) and
      nonvegetarians (n=85319) by food frequency list of self-administered
      questionnaire at baseline. The association between MS or MS components and
      different dietary groups was evaluated using Cox proportional-hazards regression
      models with adjustment for confounders. During the mean 3.75 years of follow up,
      a total 8006 MS incident cases occurred and the incidence of MS was 229 (95% CI,
      224, 234) per 10000 person year. Compared with vegans, hazard ratios of MS for
      nonvegetarians, pescovegetarians, lactovegetarians were 0.75 (95% CI, 0.64,
      0.88), 0.68 (95% CI, 0.55, 0.83) and 0.81 (95% CI, 0.67, 0.97) after adjusting
      for sex, age, education status, smoking status, drinking status, physical
      activity at work and leisure, respectively. As for MS components, nonvegetarians
      and pescovegetarians had 0.72 (95% CI, 0.62, 0.84), 0.70 (95% CI, 0.57, 0.84)
      times risk of developing low high density lipoprotein cholesterol (HDL-C), while
      nonvegetarians had 1.16 (95% CI, 1.02, 1.32) times risk of developing high
      fasting plasma glucose. Our data suggest that the vegan diets did not decrease
      the risk of metabolic syndrome compared with pescovegetarian, lactovegetarian and
      nonvegetarian diets in a Taiwanese cohort.

PMID- 21859660
TI  - The relationship between habitual dietary phosphorus and calcium intake, and bone
      mineral density in young Japanese women: a cross-sectional study.
AB  - Phosphorus and calcium are essential for bone health. There is a concern that a
      low calcium/phosphorus intake ratio resulting from low calcium intake coupled
      with high phosphorus intake may have a negative effect on bone mineral status,
      especially in Western countries. The objective of this study was to examine cross
      sectionally the influence of habitual phosphorus and calcium intake and the
      calcium/phosphorus intake ratio on the bone mineral density (BMD) in 441 young
      Japanese women (aged 18-22) whose calcium/phosphorus intake ratio was assumed to
      be lower than young Western women. We also ascertained the relationship between
      dietary intake and serum or urinary measurements of phosphorus and calcium.
      Parathyroid hormone (PTH) and 25-hydroxy vitamin D (25(OH)D) were also examined
      for 214 of the 441 subjects. Phosphorus and calcium intake and the
      calcium/phosphorus intake ratio had significant positive correlations with
      urinary phosphorus. Calcium intake and the calcium/phosphorus intake ratio
      independently had positive and significant associations with BMD in the distal
      radius adjusted for postmenarcheal age, body mass index, and physical activity.
      There were no significant associations with BMD in the lumbar spine and femoral
      neck. These results indicate that in young Japanese women, phosphorus intake did
      not have a significantly negative effect on bone mineral density, and calcium
      intake and calcium/phosphorus intake ratio had a small but significant
      association only in a site-specific manner with BMD.

PMID- 21859661
TI  - Comparison of frequently used, unexplored and newly designed indices for the
      assessment of segmental and whole body constituents.
AB  - Many constitutional indices, used as screening parameters in public health, have
      been explored (in-vivo) and applied for many years, but as yet there is no
      consensus on a universal index. This reflects confusion, or at least lack of
      agreement, about what a constitutional index should represent. The aim of this
      study was to explore the direct relationship of frequently used, unexplored and
      newly designed indices with adipose tissue masses and trunk adipose tissue
      distribution, on an anatomical 5-component model. Whole body and trunk
      composition, of 28 white Caucasian cadavers (aged 78.4+/-6.9 years), were
      determined at the anatomical tissue-system level by direct dissection. In the
      male group, the body mass index, the height/3body volume index and the
      weight/height-waist circumference-depth index showed good to excellent
      significant correlations with all adipose tissue masses (r-values between 0.75
      and 0.92) and with the internal adipose tissue/adipose tissue ratio (r-values
      between 0.59 and 0.78). In the female group, the body mass index, the
      height/3body volume index and the weight/height-waist circumference index showed
      moderate to excellent significant correlations with all adipose tissue masses (r
      values between 0.58 and 0.87) and with the internal adipose tissue/adipose tissue
      ratio (r-values between 0.52 and 0.80) and the internal adipose
      tissue/subcutaneous adipose tissue ratio (r-values between 0.48 and 0.78). The
      findings suggest that the newly designed indices (e.g. weight to height-waist
      circumference-depth index in males and weight to height-waist circumference index
      in females) are better correlates of whole body adipose tissue masses and trunk
      adipose tissue distribution than the frequently used indices.

PMID- 21859662
TI  - Predicting total fat mass from skinfold thicknesses in Japanese prepubertal
      children: a cross-sectional and longitudinal validation.
AB  - The present study was performed to develop regression based prediction equations
      for fat mass from skinfold thickness in Japanese children, and to investigate the
      cross-sectional and longitudinal validity of these equations. A total of 127
      healthy Japanese prepubertal children aged 6-12 years were randomly separated
      into two groups: the model development group (54 boys and 44 girls) and the cross
      sectional validation group (18 boys and 11 girls). Fat mass was initially
      determined by using DXA (Hologic Delphi A-QDR whole-body scanner) to provide
      reference data. Then, fat thickness was measured at triceps and subscapular using
      an Eiken-type skinfold calipers. Multiple anthropometric and DXA measures were
      obtained one year later for 28 of the original 127 subjects (longitudinal
      validation group: 14 boys and 14 girls). Strong significant correlations were
      observed between total fat mass by DXA measurement and the skinfold thickness *
      height measures by caliper in the model development group of boys and girls
      (R2=0.91-0.92, p<0.01). When these fat mass prediction equations were applied to
      the cross-sectional and longitudinal validation groups, the measured total fat
      mass was also very similar to the predicted fat mass. In addition, there were
      significant correlations between the measured and predicted total fat mass for
      boys and girls, respectively, although Bland-Altman analysis indicated a bias in
      cross-sectional validation group. Skinfold-derived prediction equations
      underestimate for obese children but are generally useful for estimating total
      fat mass in field research.

PMID- 21859663
TI  - Retrospective individual tracking of body mass index in obese and thin
      adolescents back to childhood.
AB  - The objective of this study is to track body mass index (BMI) in obese or thin
      adolescents from adolescence to childhood on an individual basis. This was
      performed at a single school with a 12-year combination education system in an
      urban city in Japan. A total of 617 students in the 3rd grade of senior high
      school (17 years old) during 2005-2009 were enrolled. Based on the Japanese BMI
      reference in childhood adjusted for age and gender, obesity and thinness were
      defined as >=90th percentile and <=5th percentile, respectively. Sixty-three
      (10.2%) and 84 (13.6%) students were found to be obese and thin, respectively.
      Complete annual tracking of BMI back to the 1st grade of elementary school (6
      years old) (1994-1998) was possible in 47 obese (74.6%) and 67 thin students
      (80.0%). The most common ages when obesity was first detected were 6-8 years for
      males, and 12-14 years for females, and the most common ages when thinness was
      first detected were 12-14 years for males, and 15-17 years for females. Once
      obesity or thinness started, these conditions remained until 17 years old in most
      students. Obese students whose obesity started earlier tended to have higher BMIs
      at 17 years old in both genders. This will be the first tracking study of BMI in
      obese and thin adolescents on an individual basis. A longitudinal study of BMI
      during childhood is useful for establishing intervention programs to prevent
      obesity or thinness in adolescence.

PMID- 21859664
TI  - The transition of Chinese dietary guidelines and food guide pagoda.
AB  - China promulgated her first food based dietary guidelines (FBDGs) in 1989. It was
      proposed by the standing board of Chinese Nutrition Society. The guidelines
      consisted of 8 items, each followed by a paragraph of explanation words. The
      second FBDGs came out in 1997, was expanded to include 3 parts i.e. guide lines
      for general population, for 7 particular population groups (infants, toddlers and
      preschool children, school-age children, adolescents, pregnant women, lactating
      mothers and the aged) and a newly formed food guide pagoda (FGP). The last
      version of the Chinese FBDGs was compelled by Chinese Nutrition Society in 2007,
      and proclaimed by the Ministry of Health in early 2008. The new guidelines kept
      the skeleton of three parts, but expanded remarkably in volume and coverage. The
      guidelines for the general population consisted of 10 items, each containing:
      core information, a discussion and reference materials. The guidelines for
      particular groups contained more subgroups, and more detailed recommendations.
      The revised pagoda kept the previous food grouping and placement but altered the
      amount of some food groups. An image of a walker and a cup of water were added to
      the side of the pagoda. Guidelines-2007 called for more coarse grains and less
      cooking oil consumption. Physical activity is also strongly recommended.

PMID- 21859665
TI  - Taking the Indonesian nutrition history to leap into betterment of the future
      generation: development of the Indonesian Nutrition Guidelines.
AB  - Nutrition history in Indonesia began in 1887, when Christiann Eijkman discovered
      the relationship between vitamin B-1 deficiency and beri-beri. In the 1950's, the
      socialization of nutrition messages started with the introduction of "Healthy
      Four Perfect Five" (Empat Sehat Lima Sempurna-ESLS). For the next 25 years after
      that, ESLS became a favorite in nutrition education and was nationally known.
      Although the ESLS was never evaluated, food consumption pattern of Indonesians
      are never balanced. Undernutrition is rampant and overnutrition emerged. In 1995
      the Indonesian food-based dietary guidelines was launched by the Ministry of
      Health, and formally incorporated into the nutrition policy. The Guide has 13
      messages. Again, the guidelines were never evaluated; in 2010 undernutrition
      persists and the prevalence of degenerative diseases increased. Thus, it is
      urgent for Indonesia to have concrete Nutrition Guidelines (Gizi Seimbang)
      covering messages like: (1) consume a variety of foods; (2) keep clean; (3) be
      active, exercise regularly; and (4) monitor body weight. The guidelines shall be
      developed for all age groups. The guidelines were tested to over 300 audiences
      and the responses were promising. Dissemination of the messages widely within the
      formal channels is compulsory. The new Nutrition Guideline messages are an open
      concept ready to be revised accordingly. It is evident that nutrition sciences
      and its application had undergone rapid changes over time and Indonesia need to
      adopt accordingly and timely. Although, outcomes may not be seen in a short time,
      longer term output will benefit future generations.

PMID- 21859666
TI  - Nutritional policies and dietary guidelines in Japan.
AB  - The national government settled on "Healthy Japan 21" as the premier preventive
      policy of lifestyle related diseases in 2000. In 2005, the effectiveness of the
      campaign was conducted, but the results did not turn out as expected. The
      Ministry of Health, Labor and Welfare made the "Japanese Food Guide Spinning Top
      (JFG-ST)" as a practical and easy way to improve eating habits for all of the
      people. The JFG-ST falls down when the balance of the diets worsens and expresses
      a stable thing in what a turn (exercise) does. Eyes down quantity to take out of
      each group per day is shown in the basic form by the 5 distinction from grain
      dishes, vegetable dishes, fish and meat dishes, milk, and fruits. In 2005, the
      Basic Law on Dietary Education was enacted to promote the dietary education about
      the importance of eating proper meals in order to solve problems such as
      inappropriate eating habits and nutrition intake, disturbances in diets,
      increases in lifestyle-related diseases, a fall in the rate of food self
      sufficiency and so forth. The Ministry of Education and Science started a program
      to train people to become "diet and nutrition teacher" in primary school. JFG- ST
      is developed in a dietary education campaign as a standard method of the dietary
      education. In May, 2011, the government has announced the second dietary
      education promotional basic plan to assume five years.

PMID- 21859667
TI  - Development and promotion of Malaysian Dietary Guidelines.
AB  - Development and promotion of dietary guidelines is one of the key activities
      outlined in the National Plan of Action for Nutrition of Malaysia for the
      prevention of nutrition-related disorders. The first official Malaysian Dietary
      Guidelines (MDG) was published in 1999 and was thoroughly reviewed and launched
      on 25 March 2010. The new MDG 2010 is a compilation of science-based nutrition
      and physical activity recommendations. These guidelines form the basis of
      consistent and scientifically sound nutrition messages for the public. There are
      14 key messages and 55 recommendations, covering the whole range of food and
      nutrition issues, from importance of consuming a variety of foods to guidance on
      specific food groups, messages to encourage physical activities, consuming safe
      food and beverages and making effective use of nutrition information on food
      labels. The MDG also has an updated food pyramid. Various efforts have been made
      to ensure that the revised MDG is disseminated to all stakeholders. The Ministry
      of Health has organised a series of workshops for nutritionists and other health
      care professionals, and the food industry. In collaboration with other
      professional bodies and the private sector, the Nutrition Society of Malaysia has
      been promoting the dissemination and usage of the MDG to the public through a
      variety of formats and channels. These include the publication of a series of
      leaflets, educational press articles, educational booklets, as well as through
      educational activities for children. It is imperative to monitor the usage and
      evaluation of these dietary messages.

PMID- 21859668
TI  - Food- based dietary guidelines for Filipinos: retrospects and prospects.
AB  - This paper reviews the formulation of positive, practical and culturally
      sensitive food-based dietary guidelines (FBDGs) to help Filipinos choose an
      adequate diet and foster wholesome food and nutrition practices to promote good
      health; and provide those concerned with a framework and reference for their task
      of educating the public on proper nutrition practices. An evidence-based approach
      to evaluate the scientific report used to develop the Nutritional Guidelines for
      Filipinos (NGF) was published summarizing the scientific bases for its
      formulation. It highlights the findings of controlled and epidemiological studies
      and review in scientific journals. The results of the nutrition surveys which
      depict the food and nutrition situation, data on dietary patterns and practices
      related to food, food availability and statistics on nutrition-related health
      problems serve as background for the guidelines. While the 2000 NGF may have
      created awareness of the link between nutrients and foods to health, the
      contribution of these guidelines to outcomes and impact on health and nutrition
      has been limited. The policy makers and stakeholders involved with FBDGs
      development should recognize that the process does not end when the messages are
      formulated. A comprehensive plan that includes implementation, assessment,
      monitoring and reformulation must be developed. Formulation of a strategy on how
      the guidelines should be implemented to improve the dietary patterns of
      Filipinos, combined with the development of a protocol for evaluation of
      implementation and impact of the guidelines will now be adopted for its revision.

PMID- 21859669
TI  - Dietary guidelines in singapore.
AB  - The 2011 Dietary Guidelines were developed with the aim of providing guidance on
      what dietary strategies can best address increasing rates of obesity and non
      communicable chronic disease in Singapore. This set of dietary guidelines was
      developed with a local expert committee based on a review of scientific
      literature and data on current dietary patterns from the 2010 National Nutrition
      Survey. Projected nutrient intakes from a diet adhering to the 2011 Dietary
      Guidelines were calculated using a local food composition database (FOCOS) and
      validated against nutrient recommendations. Acknowledging that dietary
      requirements differ between age groups, different sets of dietary guidelines have
      been developed and customised for different segments of the population. To date,
      Singapore has produced dietary guidelines for children and adolescents (focusing
      on establishing healthy lifelong eating patterns), adults (focusing on preventing
      obesity and reinforcing healthy eating patterns), and most recently, guidelines
      for older adults (>50 years of age) that address the issue of potential dietary
      insufficiency caused by age-related increases in nutrient requirements combined
      with a reduction in energy requirements. In Singapore, dietary guidelines have
      been used to inform and direct public policy and promote dietary patterns that
      meet nutrient requirements while reducing the risk of non-communicable chronic
      diseases. Examples of public policy include: national guidelines on food
      advertising and standards for food served in nursing homes; examples of public
      health promotion programmes include: the Healthier Choice Symbol Programme for
      packaged food products and programmes encouraging provision of healthier meals in
      hawker centres, restaurants, and school or workplace canteens.

PMID- 21859670
TI  - Food based dietary guidelines (FBDGs) development and promotion in Thailand.
AB  - Dietary guidelines based on 5 food groups was used as a main nutrition education
      tool until 1996 when food based dietary guidelines (FBDGs) were promoted after 2
      years of formulation and development. These FBDGs for the general population were
      designed to promote desirable and culturally acceptable eating behavior. The nine
      qualitative guidelines of Thai FBDGs include: 1. eat a variety of foods from each
      of the five food groups and maintain proper weight, 2. eat adequate rice, or
      alternate carbohydrate, 3. eat plenty of vegetables and fruits regularly, 4. eat
      fish, lean meats, eggs, legumes and pulses regularly, 5. drink sufficient amount
      of milk every day, 6. take moderate amounts of fat, 7. avoid excessive intake of
      sweet and salty foods, 8. eat clean and uncontaminated foods, and 9. avoid or
      reduce consumption of alcoholic beverages. In 1998, the quantitative part of Thai
      FBDGs or food guide model was established as "Nutrition Flag" after rigorous test
      for understanding and acceptability among consumers. Promotion and dissemination
      of the Thai FBDGs have been carried out at national and community levels through
      basic health, agricultural and educational services and training activities, as
      well as periodic campaigning via multiple communication channels and media.
      Recently in 2009, the FBDGs for infant and preschool children were introduced to
      replace the previous infant and young child feeding guidelines. There has been no
      formal evaluation on the impact of promotion of the Thai FBDGs but some periodic
      testing of knowledge and practices have shown positive results.

PMID- 21859671
TI  - Do Indonesians follow its Dietary Guidelines?: evidence related to food
      consumption, healthy lifestyle, and nutritional status within the period 2000
      2010.
AB  - Dietary Guidelines are sets of advisory statements that give dietary advice for
      population to promote nutritional well-being. They contain information on foods
      or behaviors that are encouraged and cautionary messages derived from scientific
      evidence-based reviews and specific local conditions. The Indonesian Dietary
      Guidelines consisting of 13 messages that were publicized by the Ministry of
      Health in 1995 and have not been reviewed afterward in relation to nutritional
      status and health outcome of the population. By reviewing studies on different
      age groups in the past 10 years and comparing the results with the recommended
      guidelines, this paper aims to identify if messages have been successfully
      applied and if there are relevant issues not yet covered in the guidelines. The
      reviews covered 29 out of 33 provinces, representing studies from sub-district or
      higher levels (district, provincial, national). Results showed that some messages
      have been better implemented than others; also that information for some messages
      was not available for which to conclude of its implementation. In addition, some
      practices were identified which are prevalent in several age groups and have
      important public health consequence, but not yet included in the 13-guidelines.
      These include: smoking, increased intakes of fruit and vegetables, limited
      intakes of salt and sugar, increased intakes of foods rich in zinc and calcium
      (besides iron), hand-washing before food preparation and eating, and weight
      monitoring. For infants and young children, nutrient density, feeding
      responsiveness and stimulation should be specifically highlighted. Based on the
      results, several recommendations in revising the guidelines were given.

PMID- 21859672
TI  - Food based dietary guidelines in Vietnam: progress and lessons learned.
AB  - The food based dietary guidelines (FBDGs) is a crucial tool for nutrition
      education and communication in Vietnam. Together with the changes of socio
      economic situation, Vietnam needs to deal with different nutritional problems
      including malnutrition, overweight and undiversified diets at the same time. From
      1995 to the present, three versions of FBDGs have been developed and revised in a
      period of every 5 years. The FBDGs, Food Guide Pyramid and Food Square made a
      good set of nutritional education tool which were disseminated through a wide
      range of activities and communication channels. The evaluation of FBDGs will be
      carried out before its revisions to reflect eating patterns and lifestyles of
      consumers whom the nutritional education programs wish to reach. In developing
      countries like Vietnam, the socio-economic situation is changing over short
      period of time. Therefore, the assessment of appropriateness and implementation
      progress of the FBDGs is necessary and should be done after a period of every 5
      or 10 years. The implementation of the FBDGs should be closely connected with the
      activities of the National Plan for Nutrition and should have involvement from
      multi-sectoral organizations. Training, monitoring and evaluation for
      implementation of the FBDGs are essential for the success of guiding consumers to
      convert advices into action. The lessons learned from previous FBDGs'
      implementation can be used to develop a new version of FBDGs that is more
      appropriate.

PMID- 21859673
TI  - Regulation of male fertility by bone.
AB  - A broadly held view of bone is that it is a tissue defined by its mechanical and
      scaffolding properties, whose interaction with other organs of the body is
      similar to that exerted by an armor protecting them. In the last 10 years, using
      mouse genetics, this view of bone as an assembly of inert calcified tubes has
      considerably evolved to a much more dynamic picture. It is now clear that the
      skeleton is not a simple target tissue for the hormones secreted by other organs,
      but it is an endocrine organ itself. Genetics and biochemical evidence have
      established that osteocalcin, an osteoblast-derived hormone, is an endocrine
      regulator of energy metabolism and male fertility. These novel hormonal
      connections between bone, energy metabolism, and reproduction underscore the
      concept of functional dependence in physiology and the importance of genetic
      approaches to identify novel endocrine regulations.

PMID- 21859674
TI  - Transcriptional and posttranscriptional control of cholesterol homeostasis by
      liver X receptors.
AB  - The liver X receptors (LXRs) are nuclear receptors that play central roles in the
      transcriptional control of lipid metabolism. LXRs are activated in response to
      elevated cellular cholesterol levels, allowing them to function as "cholesterol
      sensors." Once activated, LXRs induce the expression of an array of genes
      involved in cholesterol absorption, efflux, transport, and excretion. They also
      inhibit cholesterol uptake by inducing the expression of Idol, an E3 ubiquitin
      ligase that catalyzes the ubiquitination and degradation of the low-density
      lipoprotein (LDL) receptor. Synthetic LXR agonists promote cholesterol efflux in
      vivo and inhibit the development of atherosclerosis in animal models. Conversely,
      loss of LXR expression in mice leads to pathologic lipid accumulation and
      accelerated atherosclerosis. The ability of LXRs to coordinate cellular and
      systemic sterol homeostasis makes them potentially attractive targets for
      intervention in human metabolic disease.

PMID- 21859675
TI  - The social in medicine: social techniques in patient education.
AB  - The article investigates the role of the social in medicine through an empirical
      study of social technologies in Diabetes 2 and COPD patient education in Denmark.
      It demonstrates how the social at the same time is the cause of disease but also
      functions as a solution to the problem. Furthermore it suggests that the patient
      groups have an ambiguous role in medicine; they appear to be organized as
      communities of empowerment, critical of the individualizing effects of medicine,
      but at the same time these groups are embedded in medical practices, transferring
      responsibility for illness and health to the level of the citizens. The article
      provides an empirical analysis of how the social in patient education works. The
      empirical analysis challenges an existing understanding that patient groups
      automatically support healthy lifestyle changes. We point out the multiple ways
      in which the social works.

PMID- 21859676
TI  - What is human in humans? Responses from biology, anthropology, and philosophy.
AB  - Genomics has brought biology, medicine, agriculture, psychology, anthropology,
      and even philosophy to a new threshold. In this new context, the question about
      "what is human in humans" may end up being answered by geneticists, specialists
      of technoscience, and owners of biotech companies. The author defends, in this
      article, the idea that humanity is at risk in our age of genetic engineering,
      biotechnologies, and market-geared genetic research; he also argues that the
      values at the very core of our postgenomic era bring to its peak the science
      based ideology that has developed since the time of Galileo, Newton, Descartes,
      and Harvey; finally, it shows that the bioindustry has invented a new
      genomythology that goes against the scientific evidence produced by the research
      in human sciences in which life is interpreted as a language.

PMID- 21859677
TI  - African Americans' perception of risk for diabetes complications.
AB  - PURPOSE: The purpose of this exploratory, descriptive, correlational study was to
      describe the perceived risk for diabetes complications among urban African
      American adults (18-75 years old) with type 2 diabetes and to explore the
      interrelationships among illness perception, well-being, perceptions of risk for
      diabetes complications, and selected physiologic measures of diabetes risk:
      hemoglobin A1C, blood pressure, and microalbuminuria. METHODS: Urban African
      American adults with type 2 diabetes (N = 143) were recruited from 3 Chicago city
      public health clinics. They completed a demographic survey and 3 instruments: the
      Risk Perception Survey-Diabetes Mellitus, the 12-item Well-being Questionnaire,
      and the Revised Illness Perception Questionnaire. Physiologic measures included
      blood pressure, urine for microalbuminuria, and capillary blood for A1C. RESULTS:
      There was low perception of risk for diabetes complications, which was
      incongruent with the physiologic measures of risk. Less than 33% of participants
      saw themselves as being at high risk for developing any complications of
      diabetes, with the exception of vision problems (39%), despite the fact that
      physiologic measures of risk for diabetes complications were high in this sample.
      CONCLUSIONS: Risk perception was associated with well-being, perception of
      negative consequences, number of symptoms, and negative emotions related to
      diabetes. Risk perception was not in line with risk, as indicated by physiologic
      measures; thus, it is necessary to heighten this population's perception of risk
      for diabetes complications.

PMID- 21859678
TI  - Efficacy of phototherapy for newborns with hyperbilirubinemia: a cautionary
      example of an instrumental variable analysis.
AB  - BACKGROUND: Use of instrumental variables is gaining popularity as a method of
      controlling for confounding by indication in observational studies of treatments.
      OBJECTIVES: To illustrate how unmeasured instrument-level treatment substitution
      can distort effect size estimates using as an example an instrumental variable
      analysis of phototherapy for neonatal jaundice. DESIGN: Retrospective cohort
      study. SETTING: Northern California Kaiser Permanente Hospitals. PATIENTS: The
      authors studied 20,731 newborns >= 2000 g and >= 35 weeks' gestation born 1995
      2004 with a "qualifying" total serum bilirubin (TSB) level within 3 mg/dL of the
      2004 American Academy of Pediatrics (AAP) phototherapy threshold who did not have
      a positive direct antiglobulin test. MEASUREMENTS: The intervention was inpatient
      phototherapy within 8 hours of the qualifying TSB. The outcome was a TSB level
      exceeding the AAP exchange transfusion threshold <48 hours from the qualifying
      TSB. The instrumental variable was a measure of the frequency of phototherapy use
      at the newborn's birth hospital. The unmeasured substituted treatment was
      supplementation with infant formula, assessed by chart review in a sample from
      the same cohort. RESULTS: In total, 128 infants (0.62%) exceeded the exchange
      transfusion threshold. Logistic and propensity analyses yielded crude odds ratios
      of ~0.5 for phototherapy efficacy, decreasing to ~0.2 with control for
      confounding by indication. Instrumental variable analyses suggested much greater
      phototherapy efficacy (e.g., odds ratios of 0.02-0.05). However, chart reviews
      revealed greater use of infant formula (which also lowers bilirubin levels) in
      hospitals that used more phototherapy (r = 0.56; P = 0.02), an association not
      present at the individual level (r = 0.13). CONCLUSIONS: Instrumental variable
      analyses may provide biased estimates of treatment efficacy if there are
      cointerventions or confounders associated with treatment at the level of the
      instrument, although even when these associations may not exist in individuals.

PMID- 21859679
TI  - Hepatorenal syndrome in the intensive care unit.
AB  - Hepatorenal syndrome (HRS) is a functional form of acute kidney injury (AKI)
      associated with advanced liver cirrhosis or fulminant hepatic failure. Various
      new concepts have emerged since the initial diagnostic criteria and definition of
      HRS was initially published. These include better understanding of the
      pathophysiological mechanisms involved in HRS, identification of bacterial
      infection (especially spontaneous bacterial peritonitis) as the most important
      HRS-precipitating event, recognition that insufficient cardiac output plays a
      role in the occurrence of HRS, and evidence that renal failure reverses with
      pharmacotherapy. Patients with HRS are often critically ill and, by definition,
      have multiorgan failure. The purpose of this review is to provide an update on
      novel advances in HRS, with emphasis on the different aspects of management of
      these patients in the intensive care unit.

PMID- 21859681
TI  - Enabling lead discovery for histone lysine demethylases by high-throughput
      RapidFire mass spectrometry.
AB  - A high-throughput RapidFire mass spectrometry assay is described for the JMJD2
      family of Fe(2+), O(2), and alpha-ketoglutarate-dependent histone lysine
      demethylases. The assay employs a short amino acid peptide substrate,
      corresponding to the first 15 amino acid residues of histone H3, but mutated at
      two positions to increase assay sensitivity. The assay monitors the direct
      formation of the dimethylated-Lys9 product from the trimethylated-Lys9 peptide
      substrate. Monitoring the formation of the monomethylated and des-methylated
      peptide products is also possible. The assay was validated using known inhibitors
      of the histone lysine demethylases, including 2,4-pyridinedicarboxylic acid and
      an alpha-ketoglutarate analogue. With a sampling rate of 7 s per well, the
      RapidFire technology permitted the single-concentration screening of 101 226
      compounds against JMJD2C in 10 days using two instruments, typically giving Z'
      values of 0.75 to 0.85. Several compounds were identified of the 8
      hydroxyquinoline chemotype, a known series of inhibitors of the Lys9-specific
      histone demethylases. The peptide also functions as a substrate for JMJD2A,
      JMJD2D, and JMJD2E, thus enabling the development of assays for all 3 enzymes to
      monitor progress in compound selectivity. The assay represents the first report
      of a RapidFire mass spectrometry assay for an epigenetics target.

PMID- 21859680
TI  - A biochemical screen for identification of small-molecule regulators of the Wnt
      pathway using Xenopus egg extracts.
AB  - Misregulation of the Wnt pathway has been shown to be responsible for a variety
      of human diseases, most notably cancers. Screens for inhibitors of this pathway
      have been performed almost exclusively using cultured mammalian cells or with
      purified proteins. We have previously developed a biochemical assay using Xenopus
      egg extracts to recapitulate key cytoplasmic events in the Wnt pathway. Using
      this biochemical system, we show that a recombinant form of the Wnt coreceptor,
      LRP6, regulates the stability of two key components of the Wnt pathway (beta
      catenin and Axin) in opposing fashion. We have now fused beta-catenin and Axin to
      firefly and Renilla luciferase, respectively, and demonstrate that the fusion
      proteins behave similarly as their wild-type counterparts. Using this dual
      luciferase readout, we adapted the Xenopus extracts system for high-throughput
      screening. Results from these screens demonstrate signal distribution curves that
      reflect the complexity of the library screened. Of several compounds identified
      as cytoplasmic modulators of the Wnt pathway, one was further validated as a bona
      fide inhibitor of the Wnt pathway in cultured mammalian cells and Xenopus
      embryos. We show that other embryonic pathways may be amendable to screening for
      inhibitors/modulators in Xenopus egg extracts.

PMID- 21859682
TI  - High-throughput TR-FRET assays for identifying inhibitors of LSD1 and JMJD2C
      histone lysine demethylases.
AB  - Lysine demethylase 1 (LSD1) and Jumonji C domain-containing oxygenase D2C
      (JMJD2C) participate in regulating the methylation status of histone H3 lysine
      residues. In some contexts, LSD1 and JMJD2C activity causes enhanced cellular
      proliferation, which may lead to tumorigenesis. The authors explored the utility
      of time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassays,
      which employed peptides consisting of the first 21 amino acids of histone H3 in
      which lysine 4 (H3K4) or lysine 9 (H3K9) was methylated (me) to quantify LSD1 and
      JMJD2C activity. The LSD1 assay monitored demethylation of the H3K4me1 peptide
      using an antibody that recognizes H3K4me1 but not the unmethylated peptide
      product. The JMJD2C assay measured demethylation of H3K9me3 with an antibody that
      selectively recognizes H3K9me2. The optimized conditions resulted in robust
      assays (Z' > 0.7) that required only 3 to 6 nM of enzyme in a reaction volume of
      6 to 10 uL. These assays were used to compare the activity of different LSD1
      constructs and to determine the apparent K(m) of each JMJD2C substrate. Finally,
      both assays were used in a high-throughput setting for identifying demethylase
      inhibitors. Compounds discovered by these TR-FRET methods may lead to powerful
      tools for ascertaining the roles of demethylases in a cellular context and
      ultimately for potential cancer treatments.

PMID- 21859683
TI  - Prediction of off-target effects on angiotensin-converting enzyme 2.
AB  - The authors describe a structure-based strategy to identify therapeutically
      beneficial off-target effects by screening a chemical library of Food and Drug
      Administration (FDA)-approved small-molecule drugs matching pharmacophores
      defined for specific target proteins. They applied this strategy to angiotensin
      converting enzyme 2 (ACE2), an enzyme that generates vasodilatory peptides and
      promotes protection from hypertension-associated cardiovascular disease. The
      conformation-based structural selection method by molecular docking using DOCK
      allowed them to identify a series of FDA-approved drugs that enhance catalytic
      efficiency of ACE2 in vitro. These data demonstrate that libraries of approved
      drugs can be rapidly screened to identify potential side effects due to
      interactions with specific proteins other than the intended targets.

PMID- 21859684
TI  - National EQ-5D tariffs and quality-adjusted life-year estimation: comparison of
      UK, US and Danish utilities in south Swedish rheumatoid arthritis patients.
AB  - OBJECTIVE: To study how the choice of national EQ-5D tariff may affect utility
      and incremental quality-adjusted life-year (QALY) estimates. METHODS: South
      Swedish rheumatoid arthritis patients in an observational study, starting and
      continuing anti-tumour necrosis factor (TNF) monotherapy (n=54) or anti-TNF plus
      methotrexate (n=215) for 1 year during May 2002 to April 2009, were included. EQ
      5D questionnaires were completed at baseline, 3, 6 and 12 months. Utilities and
      accumulated QALY were compared using the UK, US and Danish EQ-5D tariffs.
      Utilities for all 243 possible EQ-5D health states were also compared. RESULTS:
      US utilities were generally higher than UK, with Danish falling in between. A
      substantial 1-year mean utility improvement was seen in both study groups using
      all tariffs (UK 0.28 vs 0.29; US 0.18 vs 0.19; Danish 0.20 vs 0.22). Adjusting
      for baseline differences between groups, the incremental QALY gain of combined
      treatment was 0.09 using the UK tariff, while 0.06 according to both US and
      Danish tariffs. Inter-tariff disagreement in utility and accumulated QALY varied
      irregularly across the range of utilities. CONCLUSIONS: Applying different
      national EQ-5D tariffs to the same data may result in substantially different
      incremental QALY estimates, crucial knowledge when interpreting cost-utility
      analyses. Studies using different tariffs cannot be directly compared.

PMID- 21859685
TI  - Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive,
      rheumatoid arthritis patients with an inadequate response to methotrexate: a
      randomised, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVES: To evaluate the efficacy and safety of intravenous ofatumumab, a
      fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid
      arthritis (RA) patients despite methotrexate treatment. METHODS: In this double
      blind, placebo-controlled, phase III study, active RA patients on stable
      methotrexate were randomly assigned to one course of two infusions of ofatumumab
      700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the
      ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response,
      disease activity score based on 28 joints using C-reactive protein, adverse
      events (AE) and immunogenicity. RESULTS: At week 24, a greater proportion of
      patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs
      27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All
      other key secondary efficacy endpoints were significantly improved on ofatumumab.
      Efficacy observed by 8 weeks was sustained throughout the study. The most common
      AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs
      <1%), mostly occurring on the first infusion day. Overall, first-dose infusion
      reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate;
      second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were
      reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were
      32% and 26% (serious infections <1% and 2%), respectively. One death
      (interstitial lung disease), unrelated to study drug, was reported on ofatumumab.
      No antidrug antibodies were detected in ofatumumab patients. CONCLUSIONS:
      Ofatumumab significantly improved all clinical outcomes in biological-naive,
      active RA patients with no detectable immunogenicity at week 24. No unexpected
      safety findings were identified. Trial Registry clinical trials.gov registration
      number NCT00611455.

PMID- 21859686
TI  - Simultaneous activation of the liver X receptors (LXRalpha and LXRbeta) drives
      murine collagen-induced arthritis disease pathology.
AB  - BACKGROUND: It has previously been shown that dual activation of the Liver X
      Receptors (LXRalpha and LXRbeta) by the agonist, GW3965, enhances pathology in a
      murine model of collagen-induced arthritis. OBJECTIVE: To determine whether
      LXRalpha or LXRbeta have discrete roles in driving articular inflammation.
      METHODS: Arthritis was induced in male C57BL/6 wild-type (WT), LXRalpha-/-,
      LXRbeta-/- and LXRalpha/beta double KO mice by injection with type II collagen
      and treated with 30 mg/kg of the LXR agonist GW3965 or vehicle control. The mice
      were monitored for articular inflammation and cartilage degradation by scoring
      for clinical signs of arthritis and by histological examination of the joints.
      RESULTS: Administration of 30 mg/kg GW3965 significantly increases the severity
      of arthritis in WT but not LXRalpha-/-, LXRbeta-/- or LXRalpha/beta KO mice as
      assessed by an increase in the clinical score, paw thickness and articular
      histological analysis. CONCLUSION: The proinflammatory effects associated with
      the administration of GW3965 are mediated specifically through LXRs. The absence
      of increased disease severity in the LXRalpha-/- and LXRbeta-/- GW3965-treated
      groups shows for the first time that agonism of both LXRalpha and LXRbeta is
      required to drive proinflammatory pathways in vivo.

PMID- 21859687
TI  - Vaccination leads to an aberrant FOXP3 T-cell response in non-remitting juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To investigate how meningococcal C vaccination in patients with
      remitting (oligoarticular) or progressive (polyarticular) juvenile idiopathic
      arthritis (JIA) influences the specific T-cell response to both the vaccine and
      heat shock protein 60, a regulatory auto-antigen in JIA. METHODS: Twenty six
      oligoarticular, 28 polyarticular JIA patients and 20 healthy adults were studied
      before and after MenC vaccination in a prospective follow-up study. T-cell
      proliferation assay, flow cytometry, carboxyfluorescein diacetate succinimidyl
      ester staining and multiplex immunoassay were performed to quantify and qualify
      the antigen-specific immune responses. RESULTS: Peripheral blood mononuclear
      cells (PBMC) from polyarticular JIA exemplified higher antigen-specific CD4 T
      cell proliferation, interleukin 2 (IL-2) and tumour necrosis factor alpha
      (TNFalpha) production when compared with oligoarticular JIA or healthy
      individuals after vaccination. Furthermore, in polyarticular JIA antigen-induced
      CD4+CD25(bright) or CD4+FOXP3+ T cells did not increase upon vaccination.
      CONCLUSION: Polyarticular JIA CD4+FOXP3+ T cells did not respond to vaccination
      and demonstrated a higher percentage of cells irrespective of vaccination when
      compared with oligoarticular JIA. These cells are either activated T cells and/or
      regulatory cells unable to regulate the antigen-specific immune response after
      vaccination. When compared with oligoarticular JIA, the increased IL-2 and
      TNFalpha production underline the immune hyperresponsiveness of polyarticular JIA
      PBMC to an antigenic trigger. As this may hold a risk for derailment, these
      findings could provide a cellular basis for the presumed relationship between
      environmental triggers and disease in human autoimmune diseases.

PMID- 21859688
TI  - Detection of periarticular urate deposits with dual energy CT in patients with
      acute gouty arthritis.

PMID- 21859689
TI  - On-demand anakinra treatment is effective in mevalonate kinase deficiency.
AB  - BACKGROUND: Mevalonate kinase deficiency (MKD) is a hereditary autoinflammatory
      syndrome marked by recurrent attacks of fever and inflammation. Severe enzyme
      deficiency results in mevalonic aciduria (MA) and milder deficiency in
      hyperimmunoglobulin D syndrome (HIDS). Treatment remains a challenge. OBJECTIVE:
      To observe the effect of the recombinant interleukin-1 receptor antagonist
      anakinra in patients with MKD. METHODS: A prospective observational study was
      undertaken. Two patients with MA started continuous treatment with anakinra (1-2
      mg/kg/day) and nine patients with HIDS chose between continuous treatment and on
      demand treatment (starting at first symptoms of attack, 100 mg/day or 1 mg/kg/day
      for 5-7 days). RESULTS: Anakinra induced partial remission in one patient with MA
      but there was no response in the other patient with MA. In one patient with HIDS
      continuous treatment induced complete remission for 7 months but was stopped
      because of side effects. Eight patients with HIDS preferred on-demand treatment
      from the start. This induced a clinical response (>=50% reduction in duration) in
      8 of 12 treated attacks without a change in attack frequency. Anakinra prevented
      fever attacks due to vaccination without inhibiting antibody induction. No major
      side effects were seen. CONCLUSIONS: On-demand treatment with anakinra in HIDS
      decreases the duration and severity of fever attacks. Because of the burden of
      daily injections and relatively long asymptomatic intervals of HIDS, all patients
      with HIDS preferred on-demand treatment.

PMID- 21859690
TI  - Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against
      cellular substrates: novel insights into autoantigen selection in rheumatoid
      arthritis.
AB  - OBJECTIVE: To define the relationship between autoantigen citrullination and
      different peptidylarginine deiminase (PAD) enzymes in rheumatoid arthritis (RA).
      METHODS: Citrullinated autoantigens were identified by immunoblotting control and
      ionomycin-activated human primary neutrophil lysate with RA sera. Autoantigen
      identity and citrullination sites were defined by mass spectrometry. PAD
      isoenzyme expression in human neutrophils was determined by immunoblotting. PAD
      substrate specificity was addressed in HL-60 cell lysates co-incubated with human
      recombinant PAD2, PAD3 and PAD4. RESULTS: Although prominent protein
      citrullination is observed in ionomycin-activated neutrophils, RA sera only
      recognised a limited number of these citrullinated molecules. Among these, the
      authors identified that beta and gamma-actins are citrullinated on at least 10
      arginine residues, generating a novel 47 kDa species that is frequently
      recognised by RA autoantibodies. Interestingly, the authors showed that the PAD
      enzymes expressed in human neutrophils (ie, PAD2, PAD3 and PAD4) have unique
      substrate specificities, independent of their subcellular distribution. Thus,
      only PAD2 was able to citrullinate native beta/gamma-actin, while histone H3 was
      only citrullinated by PAD4. CONCLUSION: These studies identified beta and gamma
      actins as novel citrullinated autoantigens in RA, allowing enzyme specificity
      against intracellular substrates to be addressed. The studies provide evidence
      that PAD enzymes have the intrinsic capacity to select unique protein targets.
      The authors propose that unique PAD specificity may play a role in autoantigen
      selection in RA.

PMID- 21859691
TI  - ANCA-stimulated neutrophils release BLyS and promote B cell survival: a
      clinically relevant cellular process.
AB  - OBJECTIVES: To determine a role for antineutrophil cytoplasmic antibody (ANCA)
      activated neutrophils in promoting B cell survival through the release of B
      lymphocyte stimulator (BLyS). METHODS: Neutrophil BLyS expression was measured by
      flow cytometry. Concentrations of BLyS in cell supernatants and donor serum
      samples were measured by ELISA. Cell survival assays were carried out using an
      L3055 cell line and viability measured by flow cytometry. RESULTS: Tumour
      necrosis factor alpha and formyl-Met-Leu-Phe (fMLP) treatment of non-primed
      neutrophils and treatment of primed neutrophils with anti-PR3 ANCA IgG resulted
      in a significant increase in surface expression of BLyS within 30 min which
      returned to basal levels by 2 h. Supernatants from ANCA-stimulated neutrophils
      were shown to contain increased levels of BLyS and to promote the survival of the
      centroblast cell line L3055. Serum BLyS concentrations are increased in patients
      with active ANCA-associated systemic vasculitis and these levels are increased
      further following 1-3 months of treatment with rituximab. CONCLUSIONS: ANCA
      specifically causes the release of BLyS from activated neutrophils which can
      support B cell survival in vitro. The presence of serum BLyS in active disease
      and its increase following B cell depletion suggest it is an important factor in
      disease pathogenesis and may facilitate disease relapse.

PMID- 21859692
TI  - Two-year results from an open-label, multicentre, phase III study evaluating the
      safety and efficacy of canakinumab in patients with cryopyrin-associated periodic
      syndrome across different severity phenotypes.
AB  - OBJECTIVE: Longer-term effects of prolonged selective interleukin-1beta blockade
      with canakinumab were evaluated in the largest cohort of cryopyrin-associated
      periodic syndrome (CAPS) patients studied to date. METHODS: Adult and paediatric
      CAPS patients (n=166, including canakinumab-naive and pretreated patients from
      previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (<=40 kg)
      every 8 weeks for up to 2 years. Response and relapse was assessed using scores
      for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid
      A (SAA) levels. RESULTS: Complete response was achieved in 85 of 109 canakinumab
      naive patients (78%; 79/85 patients within 8 days, and five patients between days
      10 and 21). Of 141 patients with an available relapse assessment, 90% did not
      relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the
      normal range thereafter. Median treatment duration was 414 days (29-687 days).
      Upward adjustments of dose or frequency were needed in 24.1% patients; mostly
      children and those with severe CAPS. Predominant adverse events (AE) were
      infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18
      patients (10.8%) were mainly infections and were responsive to standard
      treatment. The majority of patients (92%) reported having no injection-site
      reactions and only 8% patients reported mild-to-moderate reactions. Patients
      receiving vaccination (15%) showed normal immune response. CONCLUSIONS:
      Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided
      substantial disease control in children and adults across all CAPS phenotypes.
      Higher canakinumab doses in younger patients and more severe CAPS disease were
      efficacious in achieving complete responses without evidence of increased AE.
      TRIAL REGISTRATION NUMBER: NCT00685373 (clinicaltrials.gov).

PMID- 21859693
TI  - Bone marrow oedema predicts structural progression in a 1-year follow-up of 85
      patients with RA in remission or with low disease activity with low-field MRI.
AB  - OBJECTIVES: To identify the predictive factors of MRI-determined structural
      progression in patients with rheumatoid arthritis (RA) in remission or with low
      disease activity (LDA). METHODS: In this 1-year longitudinal study, patients with
      RA in clinical remission (disease activity score (DAS) 44<=1.6) or with LDA
      (1.6<DAS 44<=2.4) underwent low-field MRI of the dominant hand at baseline and at
      6 and 12 months. MRI images were scored by the rheumatoid arthritis MRI system
      (RAMRIS) by rheumatologists blind to clinical and biological data. Structural
      progression was defined as a change in the RAMRIS(erosion) score between baseline
      and 1 year greater than the smallest detectable difference. Predictive factors of
      structural disease progression were analysed by logistic and linear regression.
      RESULTS: 85 patients with RA in remission (n=47) or with LDA (n=38) were
      included. Their mean age was 50 +/- 13 years, 81% were female, mean disease
      duration was 35 +/- 20 months, rheumatoid factor (RF)/anti-CCP positivity was
      63%/64% and 77% had radiographic erosion. At baseline most patients showed
      inflammatory activity on MRI: 87% had at least one synovitis and 23% at least one
      location of bone marrow oedema (BME). BME at baseline was predictive of change in
      RAMRIS(erosion) (OR 1.25, 95% CI 1.09 to 1.43, p=0.0013, area under the
      curve=0.78). CONCLUSION: BME is a predictive factor of MRI-determined structural
      progression in patients with RA in clinical remission or with LDA.

PMID- 21859695
TI  - Cyclophosphamide is a highly effective and safe induction therapy in chronic
      periaortitis: a long-term follow-up of 35 patients with chronic periaortitis.

PMID- 21859694
TI  - HLA-B27 and gender independently determine the likelihood of a positive MRI of
      the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI
      follow-up study.
AB  - OBJECTIVES: To describe how inflammation on MRI of the sacroiliac joints in
      patients with recent-onset inflammatory back pain (IBP) evolves over time, and to
      study determinants of activity on MRI of the sacroiliac joint. METHODS: A 2-year
      follow-up study with annual MRI of the sacroiliac joints was conducted in
      patients with IBP of less than 2 years' duration. Images were scored for bone
      marrow oedema on short tau inversion recovery and enhancement after
      administration of gadolinium on T1. RESULTS: Of the 68 patients (38% male; mean
      age 34.9 +/- 10.3 years) enrolled, 44 had a negative baseline MRI. Of these 44
      patients, 39 patients had at least one follow-up MRI of whom six patients (15%)
      developed activity on MRI during follow-up. 24 patients (35%) had an abnormal MRI
      at baseline. In 23 of these 24 patients follow-up MRI was available. The MRI
      became negative in seven of these 23 patients (30%) during follow-up. Human
      leucocyte antigen B27 (HLA-B27) positivity and male gender determined
      independently the likelihood of a positive MRI at any time point. In an HLA-B27
      positive patient the likelihood of a positive MRI during follow-up is 88% if the
      baseline MRI is positive and 27% if the baseline MRI is negative. In an HLA-B27
      negative patient with a negative MRI at baseline the likelihood of a positive MRI
      during follow-up is less than 5%. CONCLUSIONS: A positive MRI at baseline
      predicts a positive MRI during follow-up in HLA-B27-positive patients. A negative
      MRI at baseline in HLA-B27-negative patients strongly predicts a negative MRI
      during follow-up.

PMID- 21859696
TI  - Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in
      patients with rheumatoid arthritis: implications for clinical practice.
AB  - BACKGROUND: Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients
      with rheumatoid arthritis (RA) was recently reported. OBJECTIVES: To evaluate the
      contribution of age, disease activity, medication and previous antibody levels to
      this reduced response. METHODS: 340 adult RA patients and 234 healthy controls
      were assessed before and 21 days after adjuvant-free influenza
      A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment
      and pH1N1 antibody titres were collected. Seroprotection, seroconversion and
      factor increase in geometric mean titre (GMT) were calculated and adverse events
      registered. RESULTS: RA and controls showed similar (p>0.05) prevaccination GMT
      (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant
      reduction (p<0.001) was observed in all endpoints: GMT and factor increase in
      GMT, seroprotection and seroconversion rates. Disease activity did not preclude
      seroconversion or seroprotection and remained unchanged in 97.4% of patients.
      Methotrexate was the only disease-modifying antirheumatic drug associated with
      reduced responses (p=0.001). Vaccination was well tolerated. CONCLUSIONS: The
      data confirmed both short-term anti-pH1N1 vaccine safety and, different from most
      studies with seasonal influenza, reduced seroprotection in RA patients, unrelated
      to disease activity and to most medications (except methotrexate). Extrapolation
      of immune responses from one vaccine to another may therefore not be possible and
      specific immunisation strategies (possibly booster) may be needed.
      Clinicaltrials.gov no NCT01151644.

PMID- 21859698
TI  - Pulmonary dysfunction, smoking, socioeconomic status and the risk of developing
      rheumatoid arthritis.
AB  - OBJECTIVES: Environmental risk factors are of potential interest for both
      prevention and treatment of RA. The purpose of this study was to examine the
      effect of pulmonary function, smoking and socio-economic status on the future
      risk of RA. METHODS: Between 1974 and 1992, 22 444 men and 10 902 women were
      included in the Malmo Preventive Medicine Program (MPMP). Pulmonary function was
      assessed by a standard screening spirometry. Chronic obstructive pulmonary
      disease (COPD) and restrictive pulmonary dysfunction were defined based on
      pulmonary function tests. Individuals who developed RA were identified by linking
      the MPMP database to national and local RA registers. The patients were
      classified according to the 1987 ACR criteria for RA. Four matched controls for
      every case were selected. RESULTS: We identified 290 cases of incident RA (151
      men/139 women; mean age at diagnosis 60 years). The median time from inclusion to
      diagnosis was 12 years. Forced vital capacity and forced expiratory volume within
      1 s values were similar in cases and controls, overall and also in separate
      analysis of those screened <=8 years before diagnosis. There was no association
      between COPD or restrictive pulmonary dysfunction and subsequent development of
      RA. Current smoking was a strong predictor for RA [odds ratio (OR) 1.79; 95% CI
      1.32, 2.42]. Blue-collar workers had an increased risk of RA (OR 1.54; 95% CI
      1.12, 2.10), independent of smoking. CONCLUSION: Pulmonary dysfunction did not
      predict RA, but smoking and low socio-economic status were independent risk
      factors for RA. Other effects of smoking may be important for RA susceptibility.

PMID- 21859697
TI  - Ischaemic manifestations in giant cell arteritis are associated with area level
      socio-economic deprivation, but not cardiovascular risk factors.
AB  - OBJECTIVES: To determine whether ischaemic manifestations of GCA are associated
      with pre-existing hypertension, atherosclerosis or area-level socio-economic
      deprivation. METHODS: We conducted an observational study of
      rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main
      outcome measure was ischaemic manifestations observed during active GCA: visual
      loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial
      ischaemia or scalp necrosis. RESULTS: Out of 271 patients, 222 had ischaemic
      manifestations. Adjusted odds ratios (ORs) for the influence of hypertension and
      atherosclerosis were 1.6 (95% CI 0.8, 3.1) and 1.5 (0.6, 3.5). The most striking
      finding was an association of ischaemic manifestations with increasing Index of
      Deprivation 2007 score: OR 4.2 (95% CI 1.3, 13.6) for the most-deprived quartile
      compared with the least-deprived quartile. Similar effect sizes were seen within
      each recruitment centre. Deprivation was associated with smoking and negatively
      associated with previous polymyalgia. However, neither of these variables, nor
      hypertension or atherosclerosis, appeared responsible for mediating the effect of
      deprivation on ischaemic complications. Smoking was not associated with ischaemic
      manifestations. Median symptom duration before treatment was 30 days; after
      adjusting for symptom duration, the OR for ischaemic complications was 3.2 (95%
      CI 1.0, 10.8) for the most-deprived quartile compared with the least-deprived
      quartile. CONCLUSIONS: In GCA, area-level socio-economic deprivation was
      associated with ischaemic manifestations: this was not mediated by traditional
      cardiovascular risk factors. These findings are novel and require replication.
      Delay between first symptoms and treatment may play a role. Public awareness
      campaigns about GCA should aim especially to engage individuals living in more
      deprived areas to encourage early presentation and prompt treatment.

PMID- 21859699
TI  - Effectiveness of biologics in rheumatology: improving the evidence base.

PMID- 21859700
TI  - An overview of models used in economic analyses of biologic therapies for
      arthritis--from current diversity to future consensus.
AB  - A number of cost-effectiveness models have been developed with the aim of
      providing guidance for decision making on biologic therapies for the management
      of inflammatory joint disease. The findings of these analyses can differ
      markedly, and these differences can undermine the credibility of such models if
      unexplained. To allow differences between models to be identified more easily, we
      define six components common to all models-initial response, longer term disease
      progression, mortality, quality-adjusted life year estimation, resource use and
      the selection and interpretation of data. We give examples of divergent
      approaches taken by model structures to the same issue, and explore the impact of
      divergence on model results, with particular focus on two models that have
      reported substantially different estimates for the cost-effectiveness of third
      line etanercept vs conventional DMARD. The sensitivity of results to a particular
      assumption made in a model will depend on the decision problem and assumptions
      made elsewhere in the model, highlighting the importance of guidance throughout
      model development. To some extent, guidance from bodies such as the National
      Institute of Health and Clinical Excellence can be used to determine which
      approach should be preferred where models differ. However, there is a pressing
      need for clinical input and guidance before consensus can be reached on the most
      credible model(s) to use for decision support.

PMID- 21859701
TI  - Are head-to-head trials of biologics needed? The role of value of information
      methods in arthritis research.
AB  - Reimbursement decisions are typically based on cost-effectiveness analyses. While
      a cost-effectiveness analysis can identify the optimum strategy, there is usually
      some degree of uncertainty around this decision. Sources of uncertainty include
      statistical sampling error in treatment efficacy measures, underlying baseline
      risk, utility measures and costs, as well as uncertainty in the structure of the
      model. The optimal strategy is therefore only optimal on average, and a decision
      to adopt this strategy might still be the wrong decision if all uncertainty could
      be eliminated. This means that there is a quantifiable expected (average) loss
      attaching to decisions made under uncertainty, and hence a value in collecting
      information to reduce that uncertainty. Value of information (VOI) analyses can
      be used to provide guidance on whether more research would be cost-effective,
      which particular model inputs (parameters) have the most bearing on decision
      uncertainty, and can also help with the design and sample size of further
      research. Here, we introduce the key concepts in VOI analyses, and highlight the
      inputs required to calculate it. The adoption of the new biologic treatments for
      RA and PsA tends to be based on placebo-controlled trials. We discuss the
      possible role of VOI analyses in deciding whether head-to-head comparisons of the
      biologic therapies should be carried out, illustrating with examples from other
      fields. We emphasize the need for a model of the natural history of RA and PsA,
      which reflects a consensus view.

PMID- 21859703
TI  - Use of biologic agents in rheumatoid arthritis: introduction.

PMID- 21859702
TI  - The Sheffield rheumatoid arthritis health economic model.
AB  - The Sheffield RA health economic model has been used in several published cost
      effectiveness analyses in both the UK and internationally to evaluate different
      treatments for patients with RA. This article presents the key methods and
      assumptions that underpin the model, including justifications for using an
      individual patient sampling methodology, and why the model has used the HAQ to
      track disease activity. The article also details how trial and observational data
      are used in the model to address specific questions. The model has been used to
      support health policy in both the UK and internationally, although the limited
      evidence still provides a challenge when using an economic model to determine the
      cost-effectiveness of RA treatments. The results of analyses using the Sheffield
      RA model are presented. The limitations of the model are discussed, and
      improvements are continually required to provide a model that is appropriate to
      address health economic questions in the future. The Sheffield RA model continues
      to be used and refined, and allows health economic questions to be answered using
      a transparent and flexible modelling methodology.

PMID- 21859704
TI  - Development of the Birmingham Rheumatoid Arthritis Model: past, present and
      future plans.
AB  - The Birmingham Rheumatoid Arthritis Model (BRAM) has been developed over a number
      of years to inform several appraisals of biologic drugs by the Technology
      Appraisals Committee of the UK National Institute for Health and Clinical
      Excellence. This article describes the processes used in the construction of the
      different versions of the BRAM.

PMID- 21859705
TI  - Modelling the cost-effectiveness of biologic treatments for psoriatic arthritis.
AB  - OBJECTIVES: A probabilistic model was developed to determine the cost
      effectiveness of three biologics, etanercept, infliximab and adalimumab, compared
      with palliative care for the treatment of active and progressive PsA in patients
      who have an inadequate response to standard treatment (including DMARDs).
      METHODS: A previous model was revised to evaluate the impact of biologics on both
      skin and joint disease and to include new evidence from the clinical review and
      evidence synthesis. Initial response to biologics was determined using the PsA
      response criteria. The impact of biologics on the arthritis component of the
      disease is then modelled via a change in the HAQ and the impact of the psoriasis
      component measured using the Psoriasis Area and Severity Index. RESULTS: For PsA
      patients with mild to moderate skin disease, the incremental cost-effectiveness
      ratio (ICER) for etanercept vs palliative care is around L18 000, and the ICER
      for infliximab vs etanercept is around L44 000 per quality-adjusted life year
      (QALY). Adalimumab is extendedly dominated. The probability that etanercept is
      cost effective is 0.436 at a threshold of L20 000 per QALY. Etanercept is also
      likely to be cost effective for patients with moderate to severe psoriasis or
      negligible skin involvement. CONCLUSIONS: Further investigation is required to
      reduce uncertainties around a number of model parameters, in particular the
      length of time over which biologics are assumed to be effective and the
      progression of HAQ on and off treatment.

PMID- 21859706
TI  - A clinician's critique of rheumatoid arthritis health economic models.
AB  - Modelling cost-effectiveness of new drugs for RA has become increasingly
      prevalent and sophisticated. This situation has arisen largely because regulatory
      agencies, such as the National Institute for Health and Clinical Excellence, have
      demanded models from industry and have commissioned independent models. Many
      technical aspects of health economic models have converged-yet the results of
      models differ greatly. These differences can be accounted for in large part by
      differences in assumptions about the nature of patients likely to be treated;
      likely treatment sequences; likely responses to treatment; likely continuation on
      drug and likely disease progression, in particular. Such parameters cannot be
      fixed and evolve with changing practice and are ideally captured by contemporary
      data. Importantly, data from the local setting to which a health economic problem
      is applied are necessary, but in the absence of ideal sources, for the many
      contributions needed, considerable differences in opinion and biases are
      commonplace. In the final analysis, all models are just that, models, and as such
      an approximation of real life. Thus, although considerable heat is generated
      during debates about model parameters, model outputs may just yield sufficient
      light for regulatory agencies allocating resources.

PMID- 21859707
TI  - Indirect and mixed treatment comparisons in arthritis research.
AB  - Evidence for the efficacy of biologic therapies in inflammatory arthritis comes
      overwhelmingly from placebo-controlled trials. Increasingly, however, authorities
      responsible for purchasing and reimbursement have tried to determine whether
      there are differences between these powerful new therapies, which would lead them
      to recommend some in preference to others, either on grounds of efficacy or cost
      effectiveness. In the absence of head-to-head trial comparisons, indirect
      comparisons may be used. Furthermore, network meta-analysis, also known as mixed
      treatment comparisons can combine information from trials in a connected network.
      These methods allow inferences about head-to-head comparisons even when there is
      little or no head-to-head evidence, which has caused some concern. In this
      article we briefly review these methodologies and describe results from recent
      applications to inflammatory arthritis in the clinical literature. We then focus
      on how the methodologies are used in decision making, taking as an illustration
      some recent technology appraisals conducted by the National Institute for Health
      and Clinical Excellence in the UK. We conclude that, in practice, the key
      decisions have been based on results from placebo-controlled trials.

PMID- 21859708
TI  - Fatty acids suppress autophagic turnover in beta-cells.
AB  - Recent studies have shown that autophagy is essential for proper beta-cell
      function and survival. However, it is yet unclear under what pathogenic
      conditions autophagy is inhibited in beta-cells. Here, we report that long term
      exposure to fatty acids and glucose block autophagic flux in beta-cells,
      contributing to their toxic effect. INS1 cells expressing GFP-LC3 (an
      autophagosome marker) were treated with 0.4 mm palmitate, 0.4 mm oleate, and
      various concentrations of glucose for 22 h. Kinetics of the effect of fatty acids
      on autophagy showed a biphasic response. During the second phase of autophagy,
      the size of autophagosomes and the content of autophagosome substrates (GFP-LC3,
      p62) and endogenous LC3 was increased. During the same phase, fatty acids
      suppressed autophagic degradation of long lived protein in both INS1 cells and
      islets. In INS1 cells, palmitate induced a 3-fold decrease in the number and the
      acidity of Acidic Vesicular Organelles. This decrease was associated with a
      suppression of hydrolase activity, suppression of endocytosis, and suppression of
      oxidative phosphorylation. The combination of fatty acids with glucose
      synergistically suppressed autophagic turnover, concomitantly suppressing insulin
      secretion. Rapamycin treatment resulted in partial reversal of the inhibition of
      autophagic flux, the inhibition of insulin secretion, and the increase in cell
      death. Our results indicate that excess nutrient could impair autophagy in the
      long term, hence contributing to nutrient-induced beta-cell dysfunction. This may
      provide a novel mechanism that connects diet-induced obesity and diabetes.

PMID- 21859709
TI  - Src regulates Tyr(20) phosphorylation of transferrin receptor-1 and potentiates
      breast cancer cell survival.
AB  - Transferrin receptor 1 (TfR1) is a ubiquitous type II membrane receptor with 61
      amino acids in the N-terminal cytoplasmic region. TfR1 is highly expressed in
      cancer cells, particularly under iron deficient conditions. Overexpression of
      TfR1 is thought to meet the increased requirement of iron uptake necessary for
      cell growth. In the present study, we used transferrin (Tf), a known ligand of
      TfR1, and gambogic acid (GA), an apoptosis-inducing agent and newly identified
      TfR1 ligand to investigate the signaling role of TfR1 in breast cancer cells. We
      found that GA but not Tf induced apoptosis in a TfR1-dependent manner in breast
      cancer MDA-MB-231 cells. Estrogen receptor-positive MCF-7 cells lack caspase-3
      and were not responsive to GA treatment. GA activated the three major signaling
      pathways of the MAPK family, as well as caspase-3, -8, and Poly(ADP
      ribose)polymerase apoptotic pathway. Interestingly, only Src inhibitor PP2
      greatly sensitized the cells to GA-mediated apoptosis. Further investigations by
      confocal fluorescence microscopy and immunoprecipitation revealed that Src and
      TfR1 are constitutively bound. Using TfR1-deficient CHO TRVB cells, point
      mutation studies showed that Tyr(20) within the (20)YTRF(23) motif of the
      cytoplasmic region of TfR1 is the phosphorylation site by Src. TfR1 Tyr(20)
      phosphomutants were more sensitive to GA-mediated apoptosis. Our results indicate
      that, albeit its iron uptake function, TfR1 is a signaling molecule and tyrosine
      phosphorylation at position 20 by Src enhances anti-apoptosis and potentiates
      breast cancer cell survival.

PMID- 21859710
TI  - Modulation of prothrombinase assembly and activity by phosphatidylethanolamine.
AB  - Constituents of platelet membranes regulate the activity of the prothrombinase
      complex. We demonstrate that membranes containing phosphatidylcholine and
      phosphatidylethanolamine (PE) bind factor Va with high affinity (K(d) = ~10 nm)
      in the absence of phosphatidylserine (PS). These membranes support formation of a
      60-70% functional prothrombinase complex at saturating factor Va concentrations.
      Although reduced interfacial packing does contribute to factor Va binding in the
      absence of PS, it does not correlate with the enhanced activity of the Xa-Va
      complex assembled on PE-containing membranes. Instead, specific protein-PE
      interactions appear to contribute to the effects of PE. In support of this,
      soluble C6PE binds to recombinant factor Va(2) (K(d) = ~6.5 MUm) and to factor Xa
      (K(d) = ~91 MUm). C6PE and C6PS binding sites of factor Xa are specific,
      distinct, and linked, because binding of one lipid enhances the binding and
      activity effects of the other. C6PE triggers assembly (K(d)(app) = ~40 nm) of a
      partially active prothrombinase complex between factor Xa and factor Va(2),
      compared with K(d)(app) for C6PS ~2 nm. These findings provide new insights into
      the possible synergistic roles of platelet PE and PS in regulating thrombin
      formation, particularly when exposed membrane PS may be limiting.

PMID- 21859711
TI  - Isolation of a TRAIL antagonist from the serum of HIV-infected patients.
AB  - Virus-host interactions are characterized by the selection of adaptive mechanisms
      by which to evade pathogenic and defense mechanisms, respectively. In primary T
      cells infected with HIV, HIV infection up-regulates TNF-related apoptosis
      inducing ligand (TRAIL) and death-inducing TRAIL receptors, but blockade of
      TRAIL:TRAIL receptor interaction does not alter HIV-induced cell death. Instead,
      HIV infection results in a novel splice variant that we call TRAIL-short (TRAIL
      s), which antagonizes TRAIL-R2. In HIV patients, plasma TRAIL-s concentration
      increases with increasing viral load and renders cells resistant to TRAIL-induced
      death. Knockdown of TRAIL-s abrogates this resistance. We propose that TRAIL-s is
      a novel adaptive mechanism of apoptosis resistance acquired by HIV-infected cells
      to avoid their elimination by TRAIL-dependent effector mechanism.

PMID- 21859712
TI  - HIV ENV glycoprotein-mediated bystander apoptosis depends on expression of the
      CCR5 co-receptor at the cell surface and ENV fusogenic activity.
AB  - HIV-1 infections lead to a progressive depletion of CD4 cells culminating in
      AIDS. The coreceptor usage by HIV varies from CCR5 (R5) tropic early in infection
      to CXCR4 (X4) tropic in later infections. Although the coreceptor switch from R5
      to X4 tropic HIV is well associated with progression to AIDS, the role of CCR5 in
      disease progression especially in patients infected exclusively with R5 isolates
      throughout the disease remains enigmatic. To better understand the role of CCR5
      and R5 tropic HIV envelope in AIDS pathogenesis, we asked whether the levels of
      CCR5 and/or HIV Env-mediated fusion determine apoptosis of bystander cells. We
      generated CD4(+) T cell lines expressing varying levels of CCR5 on the cell
      surface to show that CCR5 expression levels correlate with bystander apoptosis
      induction. The mechanism of apoptosis involved caspase-3 activation and
      mitochondrial depolarization and was dependent on gp41 fusion activity as
      confirmed by fusion-restricted gp41 point mutants and use of the fusion inhibitor
      T20. Interestingly, lower levels of CCR5 were able to support virus replication
      in the absence of bystander apoptosis. Our findings suggest that R5 HIV-1
      mediated bystander apoptosis is dependent on both CCR5 expression levels as well
      as fusogenic activity of the Env glycoprotein.

PMID- 21859713
TI  - The antidepressant desipramine is an arrestin-biased ligand at the alpha(2A)
      adrenergic receptor driving receptor down-regulation in vitro and in vivo.
AB  - The neurobiological mechanisms of action underlying antidepressant drugs remain
      poorly understood. Desipramine (DMI) is an antidepressant classically
      characterized as an inhibitor of norepinephrine reuptake. Available evidence,
      however, suggests a mechanism more complex than simple reuptake inhibition. In
      the present study, we have characterized the direct interaction between DMI and
      the alpha(2A)-adrenergic receptor (alpha(2A)AR), a key regulator of noradrenergic
      neurotransmission with altered expression and function in depression. DMI alone
      was found to be sufficient to drive receptor internalization acutely and a robust
      down-regulation of alpha(2A)AR expression and signaling following prolonged
      stimulation in vitro. These effects are achieved through arrestin-biased
      regulation of the receptor, as DMI selectively induces recruitment of arrestin
      but not activation of heterotrimeric G proteins. Meanwhile, a physiologically
      relevant concentration of endogenous agonist (norepinephrine) was unable to
      sustain a down-regulation response. Prolonged in vivo administration of DMI
      resulted in significant down-regulation of synaptic alpha(2A)AR expression, a
      response that was lost in arrestin3-null animals. We contend that direct DMI
      driven arrestin-mediated alpha(2A)AR down-regulation accounts for the
      therapeutically desirable but mechanistically unexplained adaptive alterations in
      receptor expression associated with this antidepressant. Our results provide
      novel insight into both the pharmacology of this antidepressant drug and the
      targeting of the alpha(2A)AR in depression.

PMID- 21859714
TI  - Interferon-induced antiviral protein MxA interacts with the cellular RNA
      helicases UAP56 and URH49.
AB  - Mx proteins are a family of large GTPases that are induced exclusively by
      interferon-alpha/beta and have a broad antiviral activity against several
      viruses, including influenza A virus (IAV). Although the antiviral activities of
      mouse Mx1 and human MxA have been studied extensively, the molecular mechanism of
      action remains largely unsolved. Because no direct interaction between Mx
      proteins and IAV proteins or RNA had been demonstrated so far, we addressed the
      question of whether Mx protein would interact with cellular proteins required for
      efficient replication of IAV. Immunoprecipitation of MxA revealed its association
      with two closely related RNA helicases, UAP56 and URH49. UAP56 and its paralog
      URH49 play an important role in IAV replication and are involved in nuclear
      export of IAV mRNAs and prevention of dsRNA accumulation in infected cells. In
      vitro binding assays with purified recombinant proteins revealed that MxA formed
      a direct complex with the RNA helicases. In addition, recombinant mouse Mx1 was
      also able to bind to UAP56 or URH49. Furthermore, the complex formation between
      cytoplasmic MxA and UAP56 or URH49 occurred in the perinuclear region, whereas
      nuclear Mx1 interacted with UAP56 or URH49 in distinct dots in the nucleus. Taken
      together, our data reveal that Mx proteins exerting antiviral activity can
      directly bind to the two cellular DExD/H box RNA helicases UAP56 and URH49.
      Moreover, the observed subcellular localization of the Mx-RNA helicase complexes
      coincides with the subcellular localization, where human MxA and mouse Mx1
      proteins act antivirally. On the basis of these data, we propose that Mx proteins
      exert their antiviral activity against IAV by interfering with the function of
      the RNA helicases UAP56 and URH49.

PMID- 21859715
TI  - Genetic analysis of phage Mu Mor protein amino acids involved in DNA minor groove
      binding and conformational changes.
AB  - Gene expression during lytic development of bacteriophage Mu occurs in three
      phases: early, middle, and late. Transcription from the middle promoter, P(m),
      requires the phage-encoded activator protein Mor and the bacterial RNA
      polymerase. The middle promoter has a -10 hexamer, but no -35 hexamer. Instead
      P(m) has a hyphenated inverted repeat that serves as the Mor binding site
      overlapping the position of the missing -35 element. Mor binds to this site as a
      dimer and activates transcription by recruiting RNA polymerase. The crystal
      structure of the His-Mor dimer revealed three structural elements: an N-terminal
      dimerization domain, a C-terminal helix-turn-helix DNA-binding domain, and a beta
      strand linker between the two domains. We predicted that the highly conserved
      residues in and flanking the beta-strand would be essential for the
      conformational flexibility and DNA minor groove binding by Mor. To test this
      hypothesis, we carried out single codon-specific mutagenesis with degenerate
      oligonucleotides. The amino acid substitutions were identified by DNA sequencing.
      The mutant proteins were characterized for their overexpression, solubility, DNA
      binding, and transcription activation. This analysis revealed that the Gly-Gly
      motif formed by Gly-65 and Gly-66 and the beta-strand side chain of Tyr-70 are
      crucial for DNA binding by His-tagged Mor. Mutant proteins with substitutions at
      Gly-74 retained partial activity. Treatment with the minor groove- and GC
      specific chemical chromomycin A(3) demonstrated that chromomycin prevented His
      Mor binding but could not disrupt a pre-formed His-Mor.DNA complex, consistent
      with the prediction that Mor interacts with the minor groove of the GC-rich
      spacer in the Mor binding site.

PMID- 21859716
TI  - Comparative structural and molecular characterization of Streptococcus pneumoniae
      capsular polysaccharide serogroup 10.
AB  - Streptococcus pneumoniae serogroup 10 includes four cross-reactive capsular
      polysaccharide (CPS) serotypes (10F, 10A, 10B, and 10C). In the present study,
      the structures of CPS10B and CPS10C were determined by chemical and high
      resolution NMR methods to define the features of each serotype. Both CPS10C and
      CPS10F had beta1-6-linked Galf branches formed from the termini of linear
      repeating units by wzy-dependent polymerization through the 4-OH of subterminal
      GalNAc. The only difference between these polysaccharides was the wcrC-dependent
      alpha1-2 or wcrF-dependent alpha1-4 linkages between Gal and ribitol-5-phosphate.
      The presence of one linkage or the other also distinguished the repeating units
      of CPS10B and CPS10A. However, whereas these polysaccharides both had beta1-3
      linked Galf branches linked to GalNAc, only CPS10A had additional beta1-6-linked
      Galp branches. These Galp branches and the reaction of a CPS10A-specific
      monoclonal antibody were eliminated by deletion of wcrG from the cps10A locus. In
      contrast, deletion of this gene from the cps10B locus had no effect on the
      structure of CPS10B, thereby identifying wcrG as a pseudogene in this serotype.
      The beta1-3-linked Galf branches of CPS10A and CPS10B were eliminated by deletion
      of wcrD from each corresponding cps locus. Deletion of this gene also eliminated
      wcrG-dependent beta1-6-linked Galp branches from CPS10A, thereby identifying WcrG
      as a branching enzyme that acts on the product of WcrD. These findings provide a
      complete view of the molecular, structural, and antigenic features of CPS
      serogroup 10, as well as insight into the possible emergence of new serotypes.

PMID- 21859717
TI  - Protective role of transient pore openings in calcium handling by cardiac
      mitochondria.
AB  - Long-lasting mitochondrial permeability transition pore (mPTP) openings damage
      mitochondria, but transient mPTP openings protect against chronic cardiac stress.
      To probe the mechanism, we subjected isolated cardiac mitochondria to gradual
      Ca(2+) loading, which, in the absence of BSA, induced long-lasting mPTP opening,
      causing matrix depolarization. However, with BSA present to mimic cytoplasmic
      fatty acid-binding proteins, the mitochondrial population remained polarized and
      functional, even after matrix Ca(2+) release caused an extramitochondrial free
      [Ca(2+)] increase to >10 MUM, unless mPTP openings were inhibited. These findings
      could be explained by asynchronous transient mPTP openings allowing individual
      mitochondria to depolarize long enough to flush accumulated matrix Ca(2+) and
      then to repolarize rapidly after pore closure. Because subsequent matrix Ca(2+)
      reuptake via the Ca(2+) uniporter is estimated to be >100-fold slower than matrix
      Ca(2+) release via mPTP, only a tiny fraction of mitochondria (<1%) are
      depolarized at any given time. Our results show that transient mPTP openings
      allow cardiac mitochondria to defend themselves collectively against elevated
      cytoplasmic Ca(2+) levels as long as respiratory chain activity is able to
      balance proton influx with proton pumping. We found that transient mPTP openings
      also stimulated reactive oxygen species production, which may engage reactive
      oxygen species-dependent cardioprotective signaling.

PMID- 21859718
TI  - Structural differences in lipomannans from pathogenic and nonpathogenic
      mycobacteria that impact CD1b-restricted T cell responses.
AB  - Mannosylated molecules on the Mycobacterium tuberculosis surface are important
      determinants in the immunopathogenesis of tuberculosis. To date, much attention
      has been paid to mannose-capped lipoarabinomannan, which mediates phagocytosis
      and intracellular trafficking of M. tuberculosis by engaging the macrophage
      mannose receptor and subsequently binds to intracellular CD1b molecules for
      presentation to T cells. Another important mannosylated lipoglycan on the M.
      tuberculosis surface is lipomannan (LM). Comparative structural detail of the LMs
      from virulent and avirulent strains is limited as is knowledge regarding their
      differential capacity to be recognized by the adaptive immune response. Here, we
      purified LM from the avirulent M. smegmatis and the virulent M. tuberculosis
      H(37)R(v), performed a comparative structural biochemical analysis, and addressed
      their ability to stimulate CD1b-restricted T cell clones. We found that M.
      tuberculosis H(37)R(v) produces a large neutral LM (TB-LM); in contrast, M.
      smegmatis produces a smaller linear acidic LM (SmegLM) with a high succinate
      content. Correspondingly, TB-LM was not as efficiently presented to CD1b
      restricted T cells as SmegLM. Thus, here we correlate the structure-function
      relationships for LMs with CD1b-restricted T cell responses and provide evidence
      that the structural features of TB-LM contribute to its diminished T cell
      responsiveness.

PMID- 21859721
TI  - Introduction to spin-polarized ballistic hot electron injection and detection in
      silicon.
AB  - Ballistic hot electron transport overcomes the well-known problems of
      conductivity and spin lifetime mismatch that plague spin injection attempts in
      semiconductors using ferromagnetic ohmic contacts. Through the spin dependence of
      the mean free path in ferromagnetic thin films, it also provides a means for spin
      detection after transport. Experimental results using these techniques
      (consisting of spin precession and spin-valve measurements) with silicon-based
      devices reveals the exceptionally long spin lifetime and high spin coherence
      induced by drift-dominated transport in the semiconductor. An appropriate
      quantitative model that accurately simulates the device characteristics for both
      undoped and doped spin transport channels is described; it can be used to recover
      the transit-time distribution from precession measurements and determine the spin
      current velocity, diffusion constant and spin lifetime, constituting a spin
      'Haynes-Shockley' experiment without time-of-flight techniques. A perspective on
      the future of these methods is offered as a summary.

PMID- 21859719
TI  - Calpain-cleaved type 1 inositol 1,4,5-trisphosphate receptor (InsP(3)R1) has
      InsP(3)-independent gating and disrupts intracellular Ca(2+) homeostasis.
AB  - The type 1 inositol 1,4,5-trisphosphate receptor (InsP(3)R1) is a ubiquitous
      intracellular Ca(2+) release channel that is vital to intracellular Ca(2+)
      signaling. InsP(3)R1 is a proteolytic target of calpain, which cleaves the
      channel to form a 95-kDa carboxyl-terminal fragment that includes the
      transmembrane domains, which contain the ion pore. However, the functional
      consequences of calpain proteolysis on channel behavior and Ca(2+) homeostasis
      are unknown. In the present study we have identified a unique calpain cleavage
      site in InsP(3)R1 and utilized a recombinant truncated form of the channel (capn
      InsP(3)R1) corresponding to the stable, carboxyl-terminal fragment to examine the
      functional consequences of channel proteolysis. Single-channel recordings of capn
      InsP(3)R1 revealed InsP(3)-independent gating and high open probability (P(o))
      under optimal cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) conditions. However,
      some [Ca(2+)](i) regulation of the cleaved channel remained, with a lower P(o) in
      suboptimal and inhibitory [Ca(2+)](i). Expression of capn-InsP(3)R1 in N2a cells
      reduced the Ca(2+) content of ionomycin-releasable intracellular stores and
      decreased endoplasmic reticulum Ca(2+) loading compared with control cells
      expressing full-length InsP(3)R1. Using a cleavage-specific antibody, we
      identified calpain-cleaved InsP(3)R1 in selectively vulnerable cerebellar
      Purkinje neurons after in vivo cardiac arrest. These findings indicate that
      calpain proteolysis of InsP(3)R1 generates a dysregulated channel that disrupts
      cellular Ca(2+) homeostasis. Furthermore, our results demonstrate that calpain
      cleaves InsP(3)R1 in a clinically relevant injury model, suggesting that Ca(2+)
      leak through the proteolyzed channel may act as a feed-forward mechanism to
      enhance cell death.

PMID- 21859722
TI  - Bose-Einstein condensation of spin wave quanta at room temperature.
AB  - Spin waves are delocalized excitations of magnetic media that mainly determine
      their magnetic dynamics and thermodynamics at temperatures far below the critical
      one. The quantum-mechanical counterparts of spin waves are magnons, which can be
      considered as a gas of weakly interacting bosonic quasi-particles. Here, we
      discuss the room-temperature kinetics and thermodynamics of the magnon gas in
      yttrium iron garnet films driven by parametric microwave pumping. We show that
      for high enough pumping powers, the thermalization of the driven gas results in a
      quasi-equilibrium state described by Bose-Einstein statistics with a non-zero
      chemical potential. Further increases of the pumping power cause a Bose-Einstein
      condensation documented by an observation of the magnon accumulation at the
      lowest energy level. Using the sensitivity of the Brillouin light scattering
      spectroscopy to the degree of coherence of the scattering magnons, we confirm the
      spontaneous emergence of coherence of the magnons accumulated at the bottom of
      the spectrum, occurring if their density exceeds a critical value.

PMID- 21859723
TI  - Anomalous transport properties of the half-metallic ferromagnets Co2TiSi, Co2TiGe
      and Co2TiSn.
AB  - In this work, the theoretical and experimental investigations of Co2TiZ (Z=Si, Ge
      or Sn) compounds are reported. Half-metallic ferromagnetism is predicted for all
      three compounds with only two bands crossing the Fermi energy in the majority
      channel. The magnetic moments fulfil the Slater-Pauling rule and the Curie
      temperatures are well above room temperature. All compounds show a metallic-like
      resistivity for low temperatures up to their Curie temperature, above the
      resistivity changes to semiconducting-like behaviour. A large negative
      magnetoresistance (MR) of 55 per cent is observed for Co2TiSn at room temperature
      in an applied magnetic field of MU(0)H=4T, which is comparable to the large
      negative MRs of the manganites. The Seebeck coefficients are negative for all
      three compounds and reach their maximum values at their respective Curie
      temperatures and stay almost constant up to 950 K. The highest value achieved is 
      52 MUVK(-1) for Co2TiSn, which is large for a metal. The combination of half
      metallicity and the constant large Seebeck coefficient over a wide temperature
      range makes these compounds interesting materials for thermoelectric applications
      and further spincaloric investigations.

PMID- 21859724
TI  - Spin in organics: a new route to spintronics.
AB  - New developments in the nascent field of organic spintronics are discussed. Two
      classes of phenomena can be discerned. In hybrid organic spin valves (OSVs), an
      organic semiconducting film is sandwiched between two ferromagnetic (FM) thin
      films, aiming at magnetoresistive effects as a function of the relative alignment
      of the respective magnetization directions. Alternatively, organic
      magnetoresistance (OMAR) is achieved without any FM components, and is an
      intrinsic property of the organic semiconductor material. Some of the exciting
      characteristics of OMAR, in both electrical conductance and photoconductance, are
      presented. A systematic, combined experimental-theoretical study of sign changes
      between positive and negative magnetoresistance is shown to provide important
      insight about the underlying mechanisms of OMAR. A simple explanation of
      experimental observations is obtained by combining a 'spin-blocking' mechanism,
      an essential ingredient in the recently proposed bipolaron model, with specific
      features of the device physics of space charge limited current devices in the
      bipolar regime. Finally, we discuss possible links between the physics relevant
      for OMAR and that for OSVs. More specifically, weak hyperfine fields from the
      hydrogen atoms in organic materials are thought to be crucial for a proper
      understanding of both types of phenomena.

PMID- 21859725
TI  - Spin-transfer torque in nanoscale magnetic devices.
AB  - We discuss recent highlights from research at Cornell University, Ithaca, New
      York, regarding the use of spin-transfer torques to control magnetic moments in
      nanoscale ferromagnetic devices. We highlight progress on reducing the critical
      currents necessary to produce spin-torque-driven magnetic switching, quantitative
      measurements of the magnitude and direction of the spin torque in magnetic tunnel
      junctions, and single-shot measurements of the magnetic dynamics generated during
      thermally assisted spin-torque switching.

PMID- 21859726
TI  - Controlling spins with light.
AB  - The interaction of sub-picosecond laser pulses with magnetically ordered
      materials has developed into an extremely exciting research topic in modern
      magnetism. From the discovery of sub-picosecond demagnetization over a decade ago
      to the recent demonstration of magnetization reversal by a single 40 fs laser
      pulse, the manipulation of spins by ultrashort laser pulses has become a
      fundamentally challenging topic with a potentially high impact for future
      spintronics, data storage and manipulation, and quantum computation. We have
      recently demonstrated that one can generate ultrashort and very strong (teslas)
      magnetic field pulses via the so-called inverse Faraday effect. Such optically
      induced magnetic field pulses provide unprecedented means for the generation,
      manipulation and coherent control of spins on very short time scales. The basic
      ideas behind these so-called opto-magnetic effects will be discussed and
      illustrated with recent results, demonstrating the various possibilities of this
      new field of femto-magnetism.

PMID- 21859727
TI  - Spintronics in antiferromagnets.
AB  - Magnetic domains and the walls between are the subject of great interest because
      of the role they play in determining the electrical properties of ferromagnetic
      materials and as a means of manipulating electron spin in spintronic devices.
      However, much less attention has been paid to these effects in antiferromagnets,
      primarily because there is less awareness of their existence in antiferromagnets,
      and in addition they are hard to probe since they exhibit no net magnetic moment.
      In this paper, we discuss the electrical properties of chromium, which is the
      only elemental antiferromagnet and how they depend on the subtle arrangement of
      the antiferromagnetically ordered spins. X-ray measurement of the modulation
      wavevector Q of the incommensurate antiferromagnetic spin-density wave shows
      thermal hysteresis, with the corresponding wavelength being larger during cooling
      than during warming. The thermal hysteresis in the Q vector is accompanied with a
      thermal hysteresis in both the longitudinal and Hall resistivity. During cooling,
      we measure a larger longitudinal and Hall resistivity compared with when warming,
      which indicates that a larger wavelength at a given temperature corresponds to a
      smaller carrier density or equivalently a larger antiferromagnetic ordering
      parameter compared to a smaller wavelength. This shows that the arrangement of
      the antiferromagnetic spins directly influences the transport properties. In thin
      films, the sign of the thermal hysteresis for Q is the same as in thick films,
      but a distinct aspect is that Q is quantized.

PMID- 21859728
TI  - Spin control by application of electric current and voltage in FeCo-MgO
      junctions.
AB  - Efficient control and detection of spins are the most important tasks in
      spintronics. The current and voltage applied to a magnetic tunnel junction may
      exert a torque on the magnetic thin layer in the junction and cause its reversal
      or continuous precession. The discovery of the giant tunnelling magnetoresistance
      effect in ferromagnetic tunnelling junctions using an MgO barrier enabled us to
      obtain a large signal output from the magnetization reversal and precession.
      Also, the interplay of large spin configuration-electric conduction coupling
      provides highly nonlinear effects like the spin-torque diode effect. The negative
      resistance effect and amplification using it are predicted. A new discovery about
      a voltage-induced magnetic anisotropy change in Fe ultrathin films is also
      discussed.

PMID- 21859729
TI  - Dynamical magnetoelectric effects in multiferroic oxides.
AB  - Multiferroics with coexistent ferroelectric and magnetic orders can provide an
      interesting laboratory to test unprecedented magnetoelectric (ME) responses and
      their possible applications. One such example is the dynamical and/or resonant
      coupling between magnetic and electric dipoles in a solid. As examples of such
      dynamical ME effects, (i) the multiferroic domain wall dynamics and (ii) the
      electric dipole active magnetic responses are discussed with an overview of
      recent experimental observations.

PMID- 21859730
TI  - Alterations of red blood cell metabolome in overhydrated hereditary
      stomatocytosis.
AB  - Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic
      anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent
      cations, associated with mutations in the Rh-associated glycoprotein gene. We
      assessed the red blood cell metabolome of 4 patients with this disorder and
      showed recurrent metabolic abnormalities associated with this disease but not due
      to the diminished half-life of their erythrocytes. Glycolysis is exhausted with
      accumulation of ADP, pyruvate, lactate, and malate. Ascorbate metabolic pathway
      is altered probably due to a limited entry of dehydroascorbate. Although no major
      oxydative stress has been reported in patients with overhydrated hereditary
      stomatocytosis, we found decreased amounts of oxydized glutathione, creatine and
      ergothioneine, suggesting transporter abnormalities and/or uncharacterized
      oxydative stress. These results pinpoint major metabolic defects of overhydrated
      hereditary stomatocytosis erythrocytes and emphasize the relevance of red blood
      cell metabolomics for a better understanding of the pathophysiological bases of
      hemolytic anemia associated with erythrocyte abnormalities.

PMID- 21859731
TI  - Pathways for the regulation of hepcidin expression in anemia of chronic disease
      and iron deficiency anemia in vivo.
AB  - BACKGROUND: Increased levels of hepcidin, the master regulator of iron
      homeostasis, contribute to the diversion of iron underlying the anemia of chronic
      disease. Yet hepcidin levels are low in anemia of chronic disease with
      concomitant true iron deficiency. Here we clarify the different underlying
      pathways regulating hepcidin expression under these conditions in vivo. DESIGN
      AND METHODS: We used rat models of iron deficiency anemia, anemia of chronic
      disease and anemia of chronic disease with concomitant true iron deficiency and
      investigated upstream signaling pathways controlling hepcidin transcription in
      the liver. Protein and mRNA levels of iron metabolism genes and genes involved in
      SMAD1/5/8 and STAT3 signaling were determined by RT-PCR, Western blotting and
      immunohistochemistry. RESULTS: SMAD1/5/8 phosphorylation and in parallel hepcidin
      mRNA expression were increased in anemia of chronic disease but significantly
      down-regulated in anemia of chronic disease with concomitant iron deficiency,
      either on the basis of phlebotomy or dietary iron restriction. Iron deficiency
      resulted in reduced bone morphogenetic protein-6 expression and impaired
      SMAD1/5/8 phosphorylation and trafficking, two key events for hepcidin
      transcription. Reduced SMAD1/5/8 activity in association with phlebotomy was
      paralleled by increased expression of the inhibitory factor, SMAD7, dietary iron
      restriction appeared to impair hepcidin transactivating SMAD pathways via
      reduction of membrane bound hemojuvelin expression. CONCLUSIONS: This study
      evaluated hepcidin signaling pathways in anemia of chronic disease with/without
      concomitant iron deficiency in vivo. While iron deficiency in general decreased
      bone morphogenetic protein-6 expression, phlebotomy or dietary iron restriction
      inhibited inflammation driven SMAD1/5/8 mediated hepcidin formation by different
      pathways, indicating alternate hierarchic signaling networks as a function of the
      mode and kinetics of iron deficiency. Nonetheless, iron deficiency inducible
      regulatory pathways can reverse inflammation mediated stimulation of hepcidin
      expression.

PMID- 21859732
TI  - Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with
      t(15;17)/PML-RARA.
AB  - BACKGROUND: Combined treatment with all-trans-retinoic acid and chemotherapy is
      extremely efficient in patients with acute promyelocytic leukemia with
      t(15;17)/PML-RARA, but up to 15% of patients relapse. DESIGN AND METHODS: To
      further clarify the prognostic impact of parameters such as FLT3 mutations, we
      comprehensively characterized the relation between genetic features and outcome
      in 147 patients (aged 19.7-86.3 years) with acute promyelocytic leukemia.
      RESULTS: Internal tandem duplications of the FLT3 gene (FLT3-ITD) were detected
      in 47/147 (32.0%) and tyrosine kinase domain mutations (FLT3-TKD) in 19/147
      (12.9%) patients. FLT3-ITD or FLT3-TKD mutation status did not have a significant
      prognostic impact, whereas FLT3-ITD mutation load, as defined by a mutation/wild
      type ratio of less than 0.5 was associated with trends to a better 2-year overall
      survival rate (86.7% versus 72.7%; P=0.075) and 2-year event-free survival rate
      (84.5% versus 62.1%, P=0.023) compared to the survival rates of patients with a
      ratio of 0.5 or more. Besides the t(15;17), an additional chromosomal abnormality
      was detected in 57 of 147 cases and did not show a significant impact on
      survival. White blood cell counts of 10*10(9)/L or less versus more than
      10*10(9)/L were associated with a better 2-year overall survival rate (88.3%
      versus 69.4%, respectively; P=0.015), as was male sex (P=0.040). In multivariate
      analysis, only higher age had a significant adverse impact. CONCLUSIONS:
      Prospective trials should further investigate the clinical impact of the FLT3
      ITD/wild-type mutation load aiming to evaluate whether this parameter might be
      included in risk stratification in patients with acute promyelocytic leukemia.

PMID- 21859733
TI  - Second-generation tyrosine kinase inhibitors improve the survival of patients
      with chronic myeloid leukemia in whom imatinib therapy has failed.
AB  - BACKGROUND: It has not been clearly established whether second-generation
      tyrosine kinase inhibitors actually improve the survival of patients with chronic
      myeloid leukemia in chronic phase who are given nilotinib or dasatinib therapy
      after treatment failure with imatinib. DESIGN AND METHODS: To address this issue
      we compared the survival of 104 patients in whom first-line therapy with imatinib
      failed and who were then treated with second-generation tyrosine kinase
      inhibitors with the outcome of 246 patients in whom interferon-alpha therapy
      failed and who did not receive tyrosine kinase inhibitor therapy. RESULTS:
      Patients treated with second-generation tyrosine kinase inhibitors had longer
      overall survival than the interferon controls (adjusted relative risk= 0.28,
      P=0.0001). However this survival advantage was limited to the 64.4% of patients
      in whom imatinib failed but who achieved complete cytogenetic response with the
      subsequent tyrosine kinase inhibitor (adjusted relative risk =0.05, P=0.003),
      whereas the 35.6% of patients who failed to achieve complete cytogenetic response
      on the second or third inhibitor had similar overall survival to that of the
      controls (adjusted relative risk=0.76, P=0.65). CONCLUSIONS: Patients in whom
      imatinib treatment fails who receive sequential therapy with second-generation
      tyrosine kinase inhibitors have an enormous advantage in survival over controls
      (palliative therapy); this advantage is, however, limited to the majority of the
      patients who achieve a complete cytogenetic response.

PMID- 21859734
TI  - Bortezomib and high-dose melphalan conditioning for stem cell transplantation for
      AL amyloidosis: a pilot study.

PMID- 21859735
TI  - The proportion of activated B-cell like subtype among de novo diffuse large B
      cell lymphoma increases with age.

PMID- 21859736
TI  - Clinically defined chemotherapy-associated bowel syndrome predicts severe
      complications and death in cancer patients.
AB  - BACKGROUND: Neutropenic patients are at risk of abdominal complications and yet
      the incidence and impact of these complications on patients' morbidity and
      mortality have not been sufficiently evaluated. We aimed to assess a clinical
      rule for early detection of abdominal complications leading to death or transfer
      to intensive care in patients with chemotherapy-associated neutropenia. DESIGN
      AND METHODS: This observational multicenter study was carried out in seven German
      hematology-oncology departments. For inclusion, neutropenia of at least 5
      consecutive days was required. Risk factors for "transfer to intensive care" and
      "death" were assessed by backward-stepwise binary logistic regression analyses.
      Chemotherapy-associated bowel syndrome was defined as a combination of fever (T
      >=37.8  degrees C) and abdominal pain and/or lack of bowel movement for 72 hours
      or more. Five hundred and twenty-one neutropenic episodes were documented in 359
      patients. RESULTS: The incidence of chemotherapy-associated bowel syndrome was
      126/359 (35%) in first episodes of neutropenia. Transfer to intensive care
      occurred in 41/359 (11%) and death occurred in 17/359 (5%) first episodes.
      Chemotherapy-associated bowel syndrome and duration of neutropenia were
      identified as risk factors for transfer to intensive care (P<0.001; OR 4.753; 95%
      CI 2.297-9.833, and P=0.003; OR 1.061/d; 95% CI 1.021-1.103). Chemotherapy
      associated bowel syndrome and mitoxantrone administration were identified as risk
      factors for death (P=0.005; OR 4.611; 95% CI 1.573-13.515 and P=0.026; OR 3.628;
      95% CI 1.169-11.256). CONCLUSIONS: The occurrence of chemotherapy-associated
      bowel syndrome has a significant impact on patients' outcome. In future
      interventional clinical trials, this definition might be used as a selection
      criterion for early treatment of patients at risk of severe complications.

PMID- 21859737
TI  - Insufficient recovery of thymopoiesis predicts for opportunistic infections in
      allogeneic hematopoietic stem cell transplant recipients.
AB  - BACKGROUND: Recovery of thymopoiesis after allogeneic hematopoietic stem cell
      transplantation is considered pivotal for full immune competence. However, it is
      still unclear to what extent insufficient recovery of thymopoiesis predicts for
      subsequent opportunistic infections and non-relapse mortality. DESIGN AND
      METHODS: A detailed survey of all post-engraftment infectious complications, non
      relapse mortality and overall survival during long-term follow-up was performed
      in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning.
      Recovery of thymopoiesis was assessed using analysis of signal joint T-cell
      receptor rearrangement excision circles. The impact of recovery of thymopoiesis
      at 2, 6, 9 and 12 months post-transplantation on clinical outcome beyond those
      time points was evaluated by univariate and multivariate Cox regression analyses.
      RESULTS: The cumulative incidence of severe infections at 12 months after
      transplantation was 66% with a median number of 1.64 severe infectious episodes
      per patient. Patients in whom thymopoiesis did not recover were at significantly
      higher risk of severe infections according to multivariable analysis. Hazard
      ratios indicated 3- and 9-fold increases in severe infections at 6 and 12 months,
      respectively. Impaired recovery of thymopoiesis also translated into a higher
      risk of non-relapse mortality and outweighed pre-transplant risk factors
      including age, donor type, and disease risk-status. CONCLUSIONS: These results
      indicate that patients who fail to recover thymopoiesis after allogeneic
      hematopoietic stem cell transplantation are at very high risk of severe
      infections and adverse clinical outcome.

PMID- 21859739
TI  - Extracorporeal membrane oxygenation for severe acute respiratory failure in
      adults: NICE guidance.
AB  - Extracorporeal membrane oxygenation (ECMO) is a modified form of cardiopulmonary
      bypass that allows short-term support for potentially reversible severe acute
      respiratory and/or cardiac failure in critically ill adults and children. There
      is increasing interest in veno-venous (VV) ECMO for severe acute respiratory
      failure in adults. The National Institute for Health and Clinical Excellence has
      recently updated its interventional procedure guidance, which summarises
      available data on efficacy and safety of this procedure and provides guidance for
      clinicians wishing to undertake VV ECMO. The authors summarise and reflect on the
      guidelines and discuss some recent developments in technology and clinical
      practice of VV ECMO.

PMID- 21859738
TI  - Cytotoxic molecule-positive classical Hodgkin's lymphoma: a clinicopathological
      comparison with cytotoxic molecule-positive peripheral T-cell lymphoma of not
      otherwise specified type.
AB  - BACKGROUND: Classical Hodgkin's lymphoma is characterized by Hodgkin and Reed
      Sternberg cells, which are of B-cell origin in many cases. We recently
      highlighted the adverse prognostic significance of cytotoxic molecule expression
      in patients with classical Hodgkin's lymphoma. However, the clinical
      characteristics of cytotoxic molecule-positive classical Hodgkin's lymphoma
      remain controversial. DESIGN AND METHODS: We investigated the clinicopathological
      profiles of 32 patients with cytotoxic molecule-positive Hodgkin's lymphoma,
      comprising 23 with nodular sclerosis and 9 with mixed cellularity, and compared
      these profiles with those of 55 patients with cytotoxic molecule-positive nodal
      peripheral T-cell lymphoma, not otherwise specified and 439 patients with
      cytotoxic molecule-negative Hodgkin's lymphoma. RESULTS: The patients with
      cytotoxic molecule-positive Hodgkin's lymphoma consisted of 20 men and 12 women
      with a median age of 50 years (range, 19 to 81). All these patients had
      lymphadenopathy at presentation, and 14 showed mediastinal involvement. Physical
      findings included hepatomegaly and splenomegaly in six patients each. Four
      patients had a bulky mass, and nine showed stage IV disease. The tumor cells of
      patients with cytotoxic molecule-positive Hodgkin's lymphoma had a prototypic
      immunophenotype of CD15(+) CD30(+) CD45RO(-) fascin(+), with positivity for
      Epstein-Barr virus in 39% of cases. All patients were negative for Pax5. In
      comparison with patients with cytotoxic molecule-positive nodal peripheral T-cell
      lymphomas, not otherwise specified, patients with cytotoxic-positive Hodgkin's
      lymphoma had relatively mild clinical symptoms, similar to those of patients with
      cytotoxic molecule-negative Hodgkin's lymphoma. Regarding prognosis, the survival
      of patients with cytotoxic molecule-positive Hodgkin's lymphoma was worse than
      that of patients with cytotoxic molecule-negative Hodgkin's lymphoma (P = 0.0003)
      but better than that of patients with cytotoxic molecule-positive peripheral T
      cell lymphomas, not otherwise specified (P = 0.002). CONCLUSIONS: Cytotoxic
      molecule-positive Hodgkin's lymphoma is characterized by an unfavorable
      prognosis, even if its clinicopathological features are within the boundaries of
      classical Hodgkin's lymphoma. More effective chemotherapy for cytotoxic molecule
      positive Hodgkin's lymphoma is clearly required.

PMID- 21859740
TI  - Desmosomal protein gene mutations in patients with idiopathic dilated
      cardiomyopathy undergoing cardiac transplantation: a clinicopathological study.
AB  - BACKGROUND: Idiopathic dilated cardiomyopathy (DCM) is the most frequent
      indication for orthotopic heart transplantation. It has been suggested that
      mutations in genes encoding desmosomal proteins, more typically associated with
      arrhythmogenic right ventricular cardiomyopathy, are a cause of DCM. OBJECTIVES:
      To determine the frequency of desmosomal protein gene mutations in heart
      transplant recipients and their families and to examine histopathological
      characteristics of explanted organs from mutation carriers. METHODS: 89 unrelated
      patients aged 47.9+/-13.5 years (80% male) transplanted for end-stage DCM
      underwent genetic screening of five desmosomal genes (PKP2, DSP, DSC2, DSG2 and
      JUP). The findings were correlated with clinical features and histological
      characteristics in explanted hearts. RESULTS: Pathogenic mutations were
      identified in 12 patients (13%). Five additional patients (6%) had genetic
      variants of unknown significance. The clinical phenotype of patients with
      pathogenic mutations was indistinguishable from that observed in patients without
      mutations. Evaluation of 76 relatives from 14 families with sequence variants (11
      with pathogenic mutations and three with variants of unknown effect) identified
      38 mutation carriers, four of whom had an overt DCM phenotype. Evidence of co
      segregation of mutations with DCM phenotype was found in five families.
      Histological evaluation of explanted hearts did not show any specific features in
      patients with pathogenic mutations. CONCLUSIONS: Mutations in desmosomal genes
      are frequent in patients with advanced DCM undergoing cardiac transplantation.
      These findings emphasise the importance of familial evaluation and genetic
      counselling in patients with end-stage DCM and pose important challenges for
      current histopathological criteria for arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 21859741
TI  - Syncope following 'pill-in-the-pocket' treatment of atrial fibrillation with
      propafenone plus quinidine.

PMID- 21859742
TI  - Unusual pneumopericardium during permanent pacemaker implantation.

PMID- 21859743
TI  - Feasibility, acceptability and potential effectiveness of Dignity Therapy for
      older people in care homes: a phase II randomized controlled trial of a brief
      palliative care psychotherapy.
AB  - BACKGROUND: A pilot study of Dignity Therapy conducted with hospice patients
      reported high levels of self-reported benefits of the psychotherapy. AIM: To
      assess the feasibility, acceptability and potential effectiveness of Dignity
      Therapy to reduce distress in older people in care homes. DESIGN: A randomized
      controlled open-label trial (ISRCTN37589515). SETTING AND PARTICIPANTS: 60
      residents aged 65+ with no major cognitive impairment living in care homes in
      London, UK. INTERVENTION: Dignity Therapy, a brief palliative care psychotherapy.
      OUTCOMES: Potential effectiveness (dignity-related distress, depression,
      hopefulness, quality of life at baseline and 1 and 8-week follow-up);
      acceptability (residents' views on self-reported benefits of Dignity Therapy/the
      Dignity Therapy study); and feasibility (time taken to deliver the intervention).
      RESULTS: We randomized 60/755 (8%) residents: 29 - control, 31 - intervention. We
      found no significant differences between groups on measures of potential
      effectiveness at any time. There was a reduction in dignity-related distress
      across both groups (p = 0.026). The intervention group outperformed the control
      group on all the acceptability items at both follow-ups. Effect sizes (Cohen's d)
      ranged from small (0.25) to large (0.85). These were significant for feeling that
      Dignity Therapy/the Dignity Therapy study had made their life more meaningful at
      2-week follow-up (p = 0.04), and that it would help their families at both follow
      ups (p = 0.02 and p = 0.01, respectively). Although it was feasible to deliver
      the intervention in this setting, it took longer to complete than anticipated.
      CONCLUSIONS: Although Dignity Therapy took longer to deliver than expected, this
      intervention may be a way of enhancing the end-of-life experiences of residents.

PMID- 21859744
TI  - Immune alterations in untreated and treated multiple myeloma.
AB  - The incidence of second malignancies was shown to be increased in patients with
      multiple myeloma. Although a shared genetic predisposition or common
      environmental carcinogens may account for the occurrence of both myeloma and
      additional cancers, multiple immune defects encountered in myeloma might play an
      important role in this regard. This review explores the impairments in both
      cellular and humoral mediated immunity in multiple myeloma, linking them with
      increased susceptibility to infections and additional cancers. In addition, the
      recent therapeutic advances transformed myeloma into a chronic entity, with
      multiple relapses and salvage therapies, which may result in cumulative
      immunosuppression. Although recent reports have suggested an increased rate of
      second cancers in myeloma patients treated with lenalidomide, the true impact of
      this agent and other novel anti-myeloma therapies on the incidence of additional
      malignancies remains to be clarified.

PMID- 21859745
TI  - Possible anaphylaxis to palonoestron.
AB  - Anaphylaxis related to drug therapy with 5-HT3 antagonists, in particular,
      palonosetron has not been reported frequently in the literature. Here a case is
      presented where the patient possibly had an anaphylactic reaction to
      palonosetron. In this case report, a 40-year-old female with ovarian cancer
      developed shortness of breath and hypotension after receiving her palonosetron as
      part of her premedication for chemotherapy. The patient recovered successfully
      with fluids and supportive care. This case demonstrates that even after
      successful treatment in the past with palonosetron a patient may later develop a
      hypersensitivity to the agent.

PMID- 21859746
TI  - Genetic and BMI risks for predicting blood pressure in three generations of West
      African Dogon women.
AB  - The study of genetic polymorphisms and body mass index (BMI) among African women
      in Africa and in the United States contributes to our understanding of the
      genetic and environmental risk factors for hypertension. African American women
      have the highest prevalence of hypertension and obesity compared to other ethnic
      groups in the United States. Using a cross-sectional research design, we examined
      the effects of genetic and environmental risks of single nucleotide polymorphisms
      (SNPs) and BMI on blood pressure (BP) among three generations of West African
      Dogon women (N = 199). We genotyped six SNPs located in the candidate genes known
      to be related to hypertension. We tested the associations between these SNPs and
      systolic BP (SBP) and diastolic BP (DBP) with Fisher's exact tests, chi-square
      tests for independence, and multivariable linear mixed models. The SNP rs8179526
      (SLC4A5) was significantly associated with SBP adjusted for age, age(2), and BMI
      (p = .02). The "C" allele variant of rs8179526 (allele frequency of 0.445) was
      associated with higher SBP. This SNP did not deviate from the Hardy-Weinberg
      equilibrium (HWE) with p value of .772. The SNP * BMI interaction effects
      associated with SBP and DBP were not significant. rs8179526 is located on the
      SLC4A5 gene on chromosome 2. SLC4A5 encodes a protein that transports sodium and
      bicarbonate across cell membranes while regulating cellular pH and contains
      several SNPs linked to elevated BP. Knowledge of the SNP's effect on hypertension
      among West African women can help health practitioners educate their patients
      about genetic risks of developing hypertension.

PMID- 21859747
TI  - Effects of delayed laboratory processing on platelet serotonin levels.
AB  - BACKGROUND: Despite the availability of established guidelines for measuring
      platelet serotonin, these guidelines may be difficult to follow in a hospital
      setting where time to processing may vary from sample to sample. PURPOSE: The
      purpose of this study was to evaluate the effect of the time to processing of
      human blood samples on the stability of the enzyme-linked immunosorbent assay
      (ELISA) for the determination of platelet serotonin levels in human plasma.
      METHOD: Human blood samples collected from a convenience sample of eight healthy
      volunteers were analyzed to determine platelet serotonin levels from plasma
      collected in ethylene diamine tetra acetic acid (EDTA) tubes and stored at 4
      degrees C for 3 hr, 5 hr, 8 hr, and 12 hr. RESULTS: Refrigeration storage at 4
      degrees C for 3 hr, 5 hr, 8 hr, and 12 hr altered the platelet serotonin
      measurement when compared to immediate processing. The bias for the samples
      stored at 4 degrees C for 3 hr was 102.3 (+/-217.39 ng/10(9) platelets), for 5 hr
      was 200.1 (+/-132.76 ng/10(9) platelets), for 8 hr was 146.9 (+/-221.41 ng/10(9)
      platelets), and for 12 hr was -67.6 (+/-349.60 ng/10(9) platelets). DISCUSSION:
      Results from this study show that accurate measurement of platelet serotonin
      levels is dependent on time to processing. Researchers should therefore follow a
      standardized laboratory guideline for obtaining immediate platelet serotonin
      levels after blood sample collection.

PMID- 21859748
TI  - Therapeutic lifestyle modification program reduces plasma levels of the
      chemokines CRP and MCP-1 in subjects with metabolic syndrome.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of a 6-month
      therapeutic lifestyle modification (TLM) program on chemokines related to
      oxidative stress, inflammation, endothelial dysfunction, and arterial stiffness
      in subjects with metabolic syndrome (MetS). METHODS: The authors performed a
      randomized controlled trial, assigning 52 women (mean age 62.7 +/- 9.0 years)
      with MetS to a TLM intervention group (n = 31) or a control group (n = 21). The
      authors provided the TLM intervention group with health screening, exercise, low
      calorie diet, and health education and counseling for 6 months and instructed the
      control group to maintain their usual lifestyle behaviors. Outcome variables
      included levels of myeloperoxidase (MPO), oxidized low-density lipoprotein (LDL),
      adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hs-CRP),
      interleukin-1beta, interleukin-6, tumor necrosis factor-alpha (TNF-alpha), CD40L,
      monocyte chemotactic protein-1 (MCP-1), retinol-binding protein 4 (RBP-4),
      endothelin-1, and brachial-ankle pulse wave velocity. The authors used
      generalized estimating equation (GEE) analyses to estimate the effects of the TLM
      program. RESULTS: After the 6-month TLM program, hs-CRP levels decreased
      significantly, and MCP-1 levels increased at a significantly slower rate in the
      TLM group than they did in the control group (all p < .05). CONCLUSION: These
      results indicate that a TLM program could be effective for improving patient
      inflammatory states and may also be effective in preventing cardiovascular
      complications in subjects with MetS.

PMID- 21859749
TI  - Risk assessment and risk communication in environmental health in Poland.
AB  - Efficient prevention activities can reduce disease, caused by environmental
      factors as well as costs to the health-care system, but it is impossible without
      understanding by the society of when, where, how and why exposures occur.
      Physicians and other health-care professionals may have an important role to play
      in communication of these potential dangers as the public requires information
      from knowledgeable and trusted sources about environmental risks and methods to
      avoid them. Epidemiological study in Poland shows that the health risk awareness
      in the society is not satisfactory and improvement of communication processes is
      essential to reduce individual risk factors.

PMID- 21859750
TI  - Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus
      rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart
      disease risk factors. This post-hoc analysis compared the effects of switching to
      ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk
      hypercholesterolaemic patients with (n=368) and without (n=217) MetS who had
      previously been on statin monotherapy. Patients were randomised 1:1 to double
      blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least
      squares mean percent change from baseline and 95% confidence intervals in lipid
      efficacy parameters were calculated for the population and within subgroups.
      Treatment with ezetimibe/simvastatin was significantly more effective than
      rosuvastatin at lowering low-density lipoprotein cholesterol, total cholesterol,
      non- high-density lipoprotein cholesterol, and apolipoprotein B (all p<0.001). No
      significant differences in treatment effects were seen between the presence and
      absence of MetS. In this post-hoc analysis of high-risk hypercholesterolaemic
      patients the lipid-reducing effects of ezetimibe/simvastatin or rosuvastatin were
      not altered significantly by the presence of MetS.

PMID- 21859752
TI  - An examination of dependence power, father involvement, and judgments about
      violence in an at-risk community sample of mothers.
AB  - Individuals sometimes remain in dysfunctional, and even violent, relationships
      due to a perceived dependence on a partner. We examined the influence of
      dependence power judgments (defined by a combined assessment of mother
      commitment, perceived father commitment, and perceived father alternatives) in a
      community sample of mothers potentially bound to a relationship with the father
      of her child. We also considered the influence of perceived father involvement in
      the child's life on judgments related to dependence power. Using a survey design
      with a sample of 100 mothers (age: 16-43, M = 29.16, SD = 7.17 years old)
      enrolled in a local Early Head Start/Head Start program, we observed that a
      mother's perceived father involvement was positively associated with judgments of
      her dependence power. Furthermore, we observed that her assessment of dependence
      power was negatively associated with her tolerance for both physical and
      psychological violence as well as the use of destructive child discipline
      tactics.

PMID- 21859751
TI  - Polynucleotide phosphorylase exonuclease and polymerase activities on single
      stranded DNA ends are modulated by RecN, SsbA and RecA proteins.
AB  - Bacillus subtilis pnpA gene product, polynucleotide phosphorylase (PNPase), is
      involved in double-strand break (DSB) repair via homologous recombination (HR) or
      non-homologous end-joining (NHEJ). RecN is among the first responders to localize
      at the DNA DSBs, with PNPase facilitating the formation of a discrete RecN focus
      per nucleoid. PNPase, which co-purifies with RecA and RecN, was able to degrade
      single-stranded (ss) DNA with a 3' -> 5' polarity in the presence of Mn(2+) and
      low inorganic phosphate (Pi) concentration, or to extend a 3'-OH end in the
      presence dNDP . Mn(2+). Both PNPase activities were observed in evolutionarily
      distant bacteria (B. subtilis and Escherichia coli), suggesting conserved
      functions. The activity of PNPase was directed toward ssDNA degradation or
      polymerization by manipulating the Pi/dNDPs concentrations or the availability of
      RecA or RecN. In its dATP-bound form, RecN stimulates PNPase-mediated
      polymerization. ssDNA phosphorolysis catalyzed by PNPase is stimulated by RecA,
      but inhibited by SsbA. Our findings suggest that (i) the PNPase degradative and
      polymerizing activities might play a critical role in the transition from DSB
      sensing to end resection via HR and (ii) by blunting a 3'-tailed duplex DNA, in
      the absence of HR, B. subtilis PNPase might also contribute to repair via NHEJ.

PMID- 21859753
TI  - Help-seeking in a national sample of victimized Latino women: the influence of
      victimization types.
AB  - The current study aimed to examine formal and informal help-seeking responses to
      interpersonal victimization among a national sample of Latino women. In addition,
      an examination of help-seeking by victimization type was undertaken. Data came
      from the Sexual Assault Among Latinas (SALAS) study that obtained help-seeking
      rates among a victimized subsample of Latino women (n = 714; 35.7% of a national
      sample). Results show a majority (76.6%) of the victimized participants engaged
      in some form of help-seeking with informal resources (68.9%) more often used than
      formal (32.5%). Medical attention was the type of formal help-seeking sought most
      often among victimized women who were injured (34.7%), and parents were the most
      common source of informal help-seeking (26.6%). However, logistic regression
      analyses show that help-seeking responses were significantly affected by type of
      victimization. Latino women who experienced childhood victimization were
      significantly less likely to engage in formal and informal help-seeking. Latino
      women who experienced stalking were significantly less likely to engage in formal
      help-seeking. Victimization with a weapon was significantly related to increased
      odds of formal help-seeking. Thus, women respond to violence in a way that is
      shaped by the dynamics of the victimization experience. Practice implications
      include the need to increase knowledge and availability of formal help-seeking
      venues.

PMID- 21859755
TI  - Mediating effects of stalking victimization on gender differences in mental
      health.
AB  - Studies suggest that stalking victimization may have a serious mental health
      impact. The present article investigates gender differences in mental health and
      possible mediating effects of stalking victimization in a community sample. The
      study includes a postal survey of 665 German community residents on the
      experience of stalking and various mental health indicators. In a majority of
      mental health scales, women score poorer than men, and a higher percentage of
      women fulfill criteria for a current mental disorder and used psychotropic
      medication. However, effects of gender decrease to a nonsignificant level when
      stalking victimization is entered into the respective models. Furthermore,
      associations of stalking victimization with poor mental health, psychosocial
      functioning, and use of medication are largely comparable across gender.

PMID- 21859756
TI  - Beyond static and dynamic risk factors: the incremental validity of release
      planning for predicting sex offender recidivism.
AB  - Both desistance research and strengths-based approaches to offender
      rehabilitation suggest that attempts to reduce sex offender recidivism should
      attend to an offender's release environment. Recent research has demonstrated
      that better quality release planning is associated with reduced recidivism;
      however, whether release planning contributes significant incremental validity in
      predicting recidivism over and above static and dynamic risk factors is unclear.
      In the present study, release planning was retrospectively assessed for a sample
      of child molesters (n = 196) who had been released into the community following
      completion of a prison-based treatment program and its relative contribution to
      recidivism risk prediction was investigated. The average follow-up period was
      11.08 years, during which 13.3% of the sample were convicted of a new sexual
      offence. Hierarchical Cox regression analyses showed that release planning
      contributed additional predictive validity for sexual recidivism after
      controlling for static and dynamic risk factors. Findings suggest that assessment
      of release planning might improve accuracy of sex offender risk assessments and
      that improved release planning should contribute to reductions in recidivism.

PMID- 21859757
TI  - Being a positive bystander: male antiviolence allies' experiences of "stepping
      up".
AB  - As bystander approaches become increasingly prevalent elements of sexual and
      domestic violence prevention efforts, it is necessary to better understand the
      factors that support or impede individuals in taking positive action in the face
      of aggressive or disrespectful behavior from others. This study presents
      descriptive findings about the bystander experiences of 27 men who recently
      became involved in antiviolence against women work. More specifically, we
      describe the consistency with which respondents actively intervene in the speech
      or behavior of others, the strategies they use, and the factors they weigh as
      they deliberate taking action. Respondents report a complex and interrelated set
      of individual and contextual influences on their choices within bystander
      opportunities, which hold implications for both violence-specific models of
      bystander behavior and for prevention intervention development.

PMID- 21859758
TI  - Rape and child sexual abuse: what beliefs persist about motives, perpetrators,
      and survivors?
AB  - Rape myths are prejudicial and stereotyped beliefs about rape which persist in
      society. They may have a significant impact on those affected by rape as well as
      the performance of legal and public participants in the justice system. Rape
      myths may differ over time and within different societies and cultural settings.
      Awareness of contemporary and local rape myths is necessary if they are to be
      successfully challenged through public campaigns and other means. This study
      sought to assess the prevalence of myths concerning rape and sexual abuse in a
      national population survey.

PMID- 21859759
TI  - Exposure to intimate partner violence, peer relations, and risk for internalizing
      behaviors: a prospective longitudinal study.
AB  - The present study examines the quality of peer relations as a mediator between
      exposure to IPV (intimate partner violence) and internalizing behaviors in a
      sample of 129 preadolescents and adolescents (ages 10-18), who were interviewed
      via telephone as part of a multigenerational, prospective, longitudinal study.
      Relational victimization is also examined as a moderator of IPV exposure on
      internalizing behaviors. Results demonstrate a significant association of
      exposure to severe IPV and internalizing behaviors. Relational victimization is
      found to moderate the effects of exposure to severe IPV on internalizing
      behaviors. The present findings suggest that the effects of exposure to IPV had a
      particularly important effect on the risk for internalizing problems if the
      adolescent also experienced relational victimization. Conversely, the receipt of
      prosocial behaviors buffer against the effects of IPV exposure on internalizing
      symptoms in teen girls.

PMID- 21859761
TI  - Racial differences in the prevalence of intimate partner violence against women
      and associated factors.
AB  - Intimate partner violence against women (IPV) affects all populations, but
      significant variations among these groups have been suggested. However, research
      results on racial differences in IPV are not only inconclusive, they are also
      limited-particularly with regard to racial minorities. As a result, it has been
      challenging for practitioners and service providers in many communities to serve
      an increasing number of racial minority clients. This study used the
      Collaborative Psychiatric Epidemiology Surveys (CPES) to examine differences in
      the prevalence of IPV, and associated factors, among major race groups in the
      U.S. Included variables were age, race, financial security, employment,
      education, social network, IPV perpetration and victimization, and severity of
      IPV. The results showed that Blacks were victimized the most, followed by Whites
      and Latinos, and Asians were victimized the least. Asians were the least likely
      to be victimized by IPV, even when controlling for sociodemographic variables.
      The odds of victimization for Blacks and Latinos were not significantly different
      from Whites. Financial security and age affected IPV victimization. Those who
      perceived themselves as financially secure were less likely to be victimized than
      those who did not. The older were less likely to be victimized than the younger.
      Employment, education, and social networks did not affect victimization. Race was
      not a significant predictor of perpetration, when controlling for other
      variables. Age was the only predictor of perpetration: the older were less likely
      to perpetrate IPV than the younger.

PMID- 21859760
TI  - Prospective associations among borderline personality disorder symptoms,
      interpersonal problems, and aggressive behaviors.
AB  - This study examined the prospective relationships among borderline personality
      disorder (BPD) symptoms, interpersonal problems, and types of aggressive
      behaviors (i.e., experiencing psychological and physical victimization and
      perpetrating psychological and physical aggression) in a psychiatric sample (N =
      139) over the course of 2 years. We controlled for other PD symptoms and
      demographic variables. BPD symptoms at baseline were associated with
      interpersonal sensitivity, interpersonal ambivalence, interpersonal aggression,
      need for social approval, and lack of sociability 6 months later. In turn,
      interpersonal sensitivity predicted not experiencing physical aggression,
      interpersonal aggression predicted experiencing physical aggression and
      perpetrating both psychological and physical aggression, need for social approval
      predicted experiencing both psychological and physical aggression, and lack of
      sociability predicted perpetrating physical aggression 2 years later. Results
      demonstrated that interpersonal problems mediated the relationship between BPD
      and later violent behaviors. Our findings suggest the importance of
      distinguishing between these groups of aggressive behaviors in terms of
      etiological pathways, maintenance processes, and treatment interventions.

PMID- 21859762
TI  - Barriers to successful treatment completion in child sexual abuse survivors.
AB  - Child sexual abuse (CSA) often requires psychological treatment to address the
      symptoms of victim trauma. Barriers to entry and completion of counseling
      services can compromise long-term well-being. An integrated medical and mental
      health evaluation and treatment model of a child advocacy center (CAC) has the
      potential to reduce barriers to mental health treatment. OBJECTIVE: (a) to
      describe characteristics between CSA patients who engage versus those who do not
      engage in mental health treatment and (b) to identify factors associated with
      successful completion of mental health treatment goals. For design/setting, a
      retrospective cohort study was conducted of CSA patients (ages 3-16 years)
      referred to mental health services following a CAC assessment. Outcome variables
      included linkage with treatment and completion of treatment. Independent
      variables included demographics, abuse characteristics, and therapist
      characteristics. Data were abstracted from the CAC and billing databases.
      RESULTS: Four hundred ninety subjects were evaluated. Subjects were as follows:
      predominately female (74%), White (60%), and more than half received Medicaid
      (56%). Mean age was 8.4 years. About 52% linked with mental health services and
      39% of patients that successfully linked with mental health services completed
      therapy. Successful linkage was independently associated with referrals to other
      counseling services (AOR 8.4 [2.5, 27.7]). Successful completion of therapy was
      independently associated with caregiver participation in therapy (AOR 3.2 [1.8,
      6.0]) and if the patient was referred to other counseling services (AOR 4.1 [1.9,
      8.5]). There were no differences between subjects that linked and/or completed
      therapy and those that did not with regard to demographic characteristics or
      abuse severity. CONCLUSION: In contrast to previous reports, efforts at our CAC
      seem to overcome linkage barriers in this population. However, there remain
      challenges in achieving successful completion of treatment goals in this
      population. Engaging caregivers' involvement in therapy services had a positive
      effect with successfully achieving treatment goals.

PMID- 21859763
TI  - Specifying the role of exposure to violence and violent behavior on initiation of
      gun carrying: a longitudinal test of three models of youth gun carrying.
AB  - Two waves of longitudinal data from 1,049 African American youth living in
      extreme poverty are used to examine the impact of exposure to violence (Time 1)
      and violent behavior (Time 1) on first time gun carrying (Time 2). Multivariate
      logistic regression results indicate that (a) violent behavior (Time 1) increased
      the likelihood of initiation of gun carrying (Time 2) by 76% after controlling
      for exposure to violence at Time 1, which is consistent with the stepping stone
      model of youth gun carrying, and (b) youth who were both exposed to violence at
      Time 1 and engaged in violent behavior at Time 1 were more than 2.5 times more
      likely to initiate gun carrying at Time 2 compared to youth who had neither of
      these characteristics, which supports the cumulative risk model of youth gun
      carrying. The authors discuss the implications of these findings in clarifying
      the role of violence in the community on youth gun carrying and the primary
      prevention of youth gun violence.

PMID- 21859764
TI  - Sense and sensitivity of novel criteria for frontotemporal dementia.

PMID- 21859765
TI  - The effects of oxytocin on social cognition and behaviour in frontotemporal
      dementia.
AB  - Patients with behavioural variant frontotemporal dementia demonstrate
      abnormalities in behaviour and social cognition, including deficits in emotion
      recognition. Recent studies suggest that the neuropeptide oxytocin is an
      important mediator of social behaviour, enhancing prosocial behaviours and some
      aspects of emotion recognition across species. The objective of this study was to
      assess the effects of a single dose of intranasal oxytocin on neuropsychiatric
      behaviours and emotion processing in patients with behavioural variant
      frontotemporal dementia. In a double-blind, placebo-controlled, randomized cross
      over design, 20 patients with behavioural variant frontotemporal dementia
      received one dose of 24 IU of intranasal oxytocin or placebo and then completed
      emotion recognition tasks known to be affected by frontotemporal dementia and by
      oxytocin. Caregivers completed validated behavioural ratings at 8 h and 1 week
      following drug administrations. A significant improvement in scores on the
      Neuropsychiatric Inventory was observed on the evening of oxytocin administration
      compared with placebo and compared with baseline ratings. Oxytocin was also
      associated with reduced recognition of angry facial expressions by patients with
      behavioural variant frontotemporal dementia. Together these findings suggest that
      oxytocin is a potentially promising, novel symptomatic treatment candidate for
      patients with behavioural variant frontotemporal dementia and that further study
      of this neuropeptide in frontotemporal dementia is warranted.

PMID- 21859768
TI  - Unpicking frontotemporal lobar degeneration.

PMID- 21859767
TI  - Treatment of Leber hereditary optic neuropathy.

PMID- 21859769
TI  - Social deprivation and use of mental health legislation in New Zealand.
AB  - BACKGROUND: Low socioeconomic status has consistently been associated with poorer
      health outcomes. Few studies have used ecological analysis to explore
      relationships between area measures of deprivation and use of mental health
      legislation. METHODS: We used an ecological design to explore associations
      between two area measures of relative deprivation and the two most commonly used
      sections of New Zealand mental health legislation. RESULTS: High levels of
      relative deprivation were positively correlated with use of both acute and long
      term community care provisions of mental health legislation with the correlation
      with long-term care achieving significance (r = .518, p = .016). Low levels of
      relative deprivation showed negative correlations with use of both provisions.
      The correlation of -.493 between low levels of relative deprivation and acute
      care provisions was significant at p = .023. In stepwise regression, the
      proportion of the population aged 15-64 contributed to the model for section 11,
      but ethnicity contributed to neither model. CONCLUSION: Mental health legislation
      is used disproportionately in areas with high levels of relative deprivation. The
      results have implications for regional allocation of funding for mental health
      and social services to support community-based care. Further research is needed
      to explore other factors that may account for the regional variation.

PMID- 21859771
TI  - Antioxidant and antiapoptotic effects of capsaicin against carbon tetrachloride
      induced hepatotoxicity in rats.
AB  - The aim of the study was to evaluate the potential hepatoprotective utility of
      capsaicin against carbon tetrachloride (CCl4)-induced liver injury and to explore
      the possible mechanisms whereby this agent mediated its beneficial effects. We
      randomized 40 rats into four groups for treatment with corn oil, CCl4, capsaicin
      and both CCl4 and capsaicin, respectively, for 8 weeks. At the end of the
      experiment, blood samples were collected and used for determination of
      aspartylaminotransferase (AST), alanine aminotransferase (ALT), and total
      bilirubin, while the liver tissues were subjected to hematoxylin and eosin
      examination; evaluation of malondialdehyde (MDA), reduced glutathione (GSH) and
      active caspase-3 contents; and evaluation of superoxide dismutase (SOD), catalase
      (CAT) and glutathione-S-transferase (GST) activities. Animals treated with CCl4
      exhibited significant elevation in AST, ALT, total bilirubin and caspase-3 and
      exhibited significant decrease in activities of SOD, CAT, GST and GSH contents.
      The combination (both capsaicin and CCl4) group has preserved the liver
      histology, liver enzymes and bilirubin close to normal, exhibited significant
      induction in the activities of CAT, SOD and GST, increased the liver content of
      GSH and active caspase-3 and conversely showed significant decrease in liver MDA
      content compared to CCl4 challenged rats. Capsaicin confers an appealing
      hepatoprotective effect which might be explained partially via diminishing the
      generation of MDA, induction of antioxidant systems and inhibition of active
      caspase-3.

PMID- 21859770
TI  - Addition-subtraction osteotomy with ligamentoplasty for symptomatic trapezial
      dysplasia with metacarpal instability.
AB  - Trapeziometacarpal instability with trapezial dysplasia is a disabling condition
      long before the radiological changes of osteoarthritis appear. In dysplastic
      joints surgical soft tissue correction fails to prevent the instability,
      requiring a correction of the bony anatomy. We combined two techniques described
      in the past, an abduction osteotomy of the first metacarpal and an opening wedge
      osteotomy of the trapezium, to which we added a ligament reconstruction. The
      combination of both osteotomy techniques restores the anatomy and centres the
      forces acting across the joint. We have done this procedure 21 times since 2003
      in 18 patients. Seventeen thumbs were reviewed prospectively with a mean follow
      up of 39 (range 16-65) months. Mean QuickDASH improved by 33.9 points, the key
      pinch improved by 1.8 kg and the grip strength improved by 8.7 kg. The visual
      analogue scale for pain improved from 7.9 preoperatively to 2 postoperatively.
      This technique preserves the trapeziometacarpal joint, allowing other techniques
      to be used if painful arthritis should develop in the middle to long term.

PMID- 21859772
TI  - Acute effects of fenthion on certain oxidative stress biomarkers in various
      tissues of frogs (Rana ridibunda).
AB  - This study was aimed mainly to assess the effects of fenthion on certain
      oxidative stress biomarkers in various tissues of frogs (Rana ridibunda).
      Biomarkers selected for stress monitoring were malondialdehyde (MDA) and
      antioxidant defense system (ADS) such as reduced glutathione (GSH) level,
      glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and superoxide
      dismutase (SOD) activities in the liver, kidney, heart, and brain of frogs
      exposed to 10 and 20 ppm dosages of fenthion for 24, 48, 72, and 96 h. The
      results demonstrate an increase in MDA levels in selected tissues following
      exposure to both concentrations of fenthion. The ADS, GSH-Px, GST, SOD activities
      and GSH levels also fluctuated after 24, 48, 72, and 96 h in all the treatment
      groups compared with controls. From the evidence obtained here, it is concluded
      that the exposure of frogs to fenthion induced an increase in MDA combined with
      fluctuated ADS. This may reflect the potential role of these parameters as useful
      biomarkers for oxidative stress in amphibian species.

PMID- 21859773
TI  - Protective effect of quercetin on liver damage induced by chronic toluene
      exposure in rats.
AB  - The aim of this study was to evaluate the possible protective effects of
      quercetin (QE) on liver injury caused by chronic toluene exposure in rats. The
      rats were randomly allotted into one of three experimental groups: control,
      toluene treated and toluene treated with QE; each group contained 10 animals. The
      control group received 1 ml physiologic serum, and toluene treatment was
      performed by inhalation of 3000 ppm toluene, for 8 h/day and 6 days/week for 12
      weeks. The rats in the QE-treated groups were given QE (15 mg/kg,
      intraperitoneal) once a day for 12 weeks starting just after toluene exposure.
      Tissue samples were obtained for histopathological investigation. To date, no
      histopathological changes in the liver of rats after chronic toluene exposure by
      QE treatment have been reported. Light microscopic evaluation of liver tissue
      samples of toluene-exposed rats revealed enlarged sinusoids filled with blood. In
      addition, some of the hepatocytes showed loss of cytoplasm, and some had a
      hyperchromatic nucleus. QE treatment attenuated alterations in liver histology.
      The alpha smooth muscle actin, transforming growth factor beta-positive cells and
      the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in
      the toluene-treated group were observed to be reduced with QE treatment. The data
      indicate that QE attenuates toluene-induced liver injury, but further
      investigation is still absolutely necessary.

PMID- 21859774
TI  - Short and long-term outcome of patients with severe acute kidney injury requiring
      renal replacement therapy.
AB  - BACKGROUND: Severe acute kidney injury (AKI) occurs in 2-7% of all hospital
      admissions and is an independent poor prognostic marker. Nevertheless,
      information on the long-term outcome of AKI and the factors influencing this is
      limited. AIM: To describe the short- and long-term outcome of patients requiring
      renal replacement therapy (RRT) for severe AKI and to examine factors affecting
      patient survival and renal recovery. DESIGN AND METHODS: Single centre
      retrospective analysis of 481 consecutive patients over a period of 39 months.
      FOLLOW-UP: 12 months. PRIMARY AND SECONDARY OUTCOMES: overall mortality and RRT
      dependency at 30 days, 90 days and 1 year. RESULTS: Survival at 30 days, 90 days
      and 1 year was 54.4, 47.2 and 37.6%, respectively. RRT independency at 30 days,
      90 days and 1 year was 35.2, 27.2 and 25.8%, respectively. Of those RRT
      independent at 90 days, 55% had ongoing chronic kidney disease. There were two
      distinct groups of patients: Group A (haemofiltration in ITU) and Group B
      (intermittent haemodialysis in the renal unit). Patient survival was worse in
      Group A while RRT independence was higher. Independent predictors of survival
      included renal cause of AKI and lower CI score in Group A and renal or post-renal
      cause of AKI, younger age and the absence of malignancy in Group B. Independent
      predictors of renal recovery included the presence of sepsis in Group A and pre-
      or post-renal cause of AKI in Group B. CONCLUSIONS: The short- and long-term
      survival outcome of severe AKI requiring RRT remains poor. Among those who
      survive, a significant number either continue to require RRT or have residual
      renal impairment necessitating ongoing follow-up.

PMID- 21859775
TI  - Avian and pandemic human influenza policy in South-East Asia: the interface
      between economic and public health imperatives.
AB  - The aim of this study was to analyse the contemporary policies regarding avian
      and human pandemic influenza control in three South-East Asia countries:
      Thailand, Indonesia and Vietnam. An analysis of poultry vaccination policy was
      used to explore the broader policy of influenza A H5N1 control in the region. The
      policy of antiviral stockpiling with oseltamivir, a scarce regional resource, was
      used to explore human pandemic influenza preparedness policy. Several policy
      analysis theories were applied to analyse the debate on the use of vaccination
      for poultry and stockpiling of antiviral drugs in each country case study. We
      conducted a comparative analysis across emergent themes. The study found that
      whilst Indonesia and Vietnam introduced poultry vaccination programmes, Thailand
      rejected this policy approach. By contrast, all three countries adopted similar
      strategic policies for antiviral stockpiling in preparation. In relation to
      highly pathogenic avian influenza, economic imperatives are of critical
      importance. Whilst Thailand's poultry industry is large and principally an export
      economy, Vietnam's and Indonesia's are for domestic consumption. The introduction
      of a poultry vaccination policy in Thailand would have threatened its potential
      to trade and had a major impact on its economy. Powerful domestic stakeholders in
      Vietnam and Indonesia, by contrast, were concerned less about international trade
      and more about maintaining a healthy domestic poultry population. Evidence on
      vaccination was drawn upon differently depending upon strategic economic
      positioning either to support or oppose the policy. With influenza A H5N1 endemic
      in some countries of the region, these policy differences raise questions around
      regional coherence of policies and the pursuit of an agreed overarching goal, be
      that eradication or mitigation. Moreover, whilst economic imperatives have been
      critically important in guiding policy formulation in the agriculture sector,
      questions arise regarding whether agriculture sectoral policy is coherent with
      public health sectoral policy across the region.

PMID- 21859776
TI  - Knowledge of secondary prevention guidelines for coronary heart disease: results
      from a physicians' survey in China.
AB  - BACKGROUND: There is gap between guideline requirements and clinical practice in
      coronary disease secondary prevention. A physician's awareness and familiarity
      are essential to put these guidelines in practice. DESIGN: In 2007 a cross
      sectional questionnaire survey was conducted among physicians from cardiology
      departments in 35 tertiary hospitals in China. METHODS: The survey instrument
      contained questions to determine physicians' knowledge of guideline
      recommendations for coronary heart disease secondary prevention. These included
      treatment goals for blood pressure, dyslipidaemia and diabetes, lifestyle
      modifications and medication needs for secondary prevention. The criteria were
      based mainly on the AHA/ACC Guidelines for Secondary Prevention for Patients with
      Coronary and Atherosclerotic Vascular Disease (2006). RESULTS: Responses from 837
      physicians were deemed effective and were analysed. Knowledge of treatment goals
      for blood pressure, LDL and HbA1c were 80.8%, 84.2% and 36.2%, respectively;
      however, only 27.5% of the physicians chose all three goals correctly. Knowledge
      of lifestyle modification was poor among the physicians as only 2.3% of the
      physicians correctly answered all five questions about dietary therapy and
      aerobic exercise goals and requirements. In regard to the six basic questions
      related to medication, 87% answered correctly. Several specific questions had a
      much lower rate of being correct, showing that physicians' knowledge was not
      precise and current. CONCLUSION: Knowledge of secondary prevention, especially
      lifestyle modification, for coronary disease was poor among this group of
      physicians from tertiary hospitals. Efforts must be made to educate physicians to
      improve their knowledge and improve patient care.

PMID- 21859777
TI  - Cardiovascular risk factors in women 10 years post early preeclampsia: the
      Preeclampsia Risk EValuation in FEMales study (PREVFEM).
AB  - INTRODUCTION: Preeclampsia is a complication of pregnancy and a known risk factor
      for cardiovascular disease (CVD) later in a women's life. The best approach for
      prevention of CVD in affected young women is yet unclear. We sought to
      investigate the prevalence of cardiovascular risk factors in women at 10 years
      post preeclampsia in comparison with a reference group. METHODS: Women with a
      history of early preeclampsia (exposed), DBP >= 90 mmHg with proteinuria >= 0.3
      gram/24 h before 32 weeks of gestation, and an equal number of women after
      uncomplicated pregnancy (non-exposed) from the obstetric database of 1991-2007,
      were sent a questionnaire and invited for a cardiovascular screening programme.
      RESULTS: The current study included 339 exposed women and 332 non-exposed women,
      10 years post index-pregnancy. Systolic and diastolic blood pressures (SBP/DBP)
      were 127/86 mmHg versus 119/79 mmHg in the exposed and reference group
      respectively (p < 0.001). Exposure to early preeclampsia was associated with a
      threefold increased prevalence of hypertension (adjusted odds ratio (OR) 3.59,
      95%CI 2.48-5.20). BMI and waist circumference were 26.9 kg/m(2) and 86.5 cm in
      the exposed group and 26.2 kg/m(2) (p = 0.07) and 83 cm (p = 0.001) in the non
      exposed group. We found no differences in levels of glucose, lipids and CRP.
      Adjusted OR for the metabolic syndrome in women post preeclampsia was 2.18 (95%
      CI 1.34-3.52) compared with women in the reference group. CONCLUSION: We found a
      high prevalence of hypertension in young women at 10 years post early
      preeclampsia. More research on the timing of cardiovascular screening in these
      high-risk women is needed.

PMID- 21859779
TI  - Sedentary leisure time behavior, snacking habits and cardiovascular biomarkers:
      the Inter99 Study.
AB  - AIM: To explore the association between sedentary leisure time behavior (SLTB)
      and cardiovascular biomarkers, taking into account snacking habits, alcohol
      intake and physical activity level. DESIGN: Cross-sectional. METHODS: Study
      participants were recruited from the 5-year follow-up of a population-based
      intervention study, The Inter99 Study (1999-2006, Copenhagen, Denmark). A group
      of 6536 men and women, aged 35-65, was invited to attend a health examination and
      fill in a self-report questionnaire. Multiple linear regression analysis was
      applied. RESULTS: Response rate was 69% (N = 4511), with equal gender
      distribution and mean age of 52. SLTB (hours per day) was significantly
      positively associated with triglyceride in men (beta = 1.030, [1.013; 1.047]) and
      women (beta = 1.036, [1.022; 1.050]), non-HDL cholesterol in men (beta = 0.044,
      [0.012; 0.076]) and women (beta = 0.064, [0.035; 0.094]), waist circumference in
      men (beta = 0.835, [0.517; 1.153]) and women (beta = 1.234, [0.087; 1.598]), and
      with waist/hip ratio (WHR) in men (beta = 0.0054, [0.0036; 0.0073]) and women
      (beta = 0.0040, [0.0019; 0.0060]). The associations persisted after adjustment
      for relevant confounders, except in HDL, where the association became non
      significant in men (beta = 0.9924, [0.9839; 1.0011]) and women (beta = 0.9932,
      [0.8605; 1.0014]). CONCLUSION: SLTB appears to be an independent CVD risk factor,
      regardless of snacking habits and physical activity.

PMID- 21859780
TI  - Age and gender differences in incidence and case fatality trends for myocardial
      infarction: a 30-year follow-up. The Tromso Study.
AB  - BACKGROUND: Although the mortality of coronary heart disease (CHD) has declined
      in Western countries during the last decades, studies have suggested that the
      prevention and treatment of CHD may not have been as effective in women as in
      men. We examined gender- and age-specific trends in incidence, case fatality and
      the severity of first myocardial infarction (MI) in a large Norwegian population
      based study. DESIGN: Prospective population-based cohort study. METHODS: A total
      of 31,323 participants enrolled between 1974 and 2001 were followed throughout
      2004 for a total of 400,572 person-years. Suspected coronary events were
      adjudicated by a review of hospital records and death certificates. A total of
      1669 events fulfilled standardized criteria of first-ever fatal or non-fatal MI.
      RESULTS: In the age group 35-79 years, the age-adjusted incidence of MI declined
      significantly in men, whereas an increase was observed in women. For men and
      women >= 80 years the incidence rates remained unchanged. The severity of MI and
      the 28-day and 1-year case fatality rates declined significantly and similarly in
      men and women. CONCLUSION: Trends in MI incidence differed by sex and age; in the
      age group 35-79 years a marked decrease was observed among men but an increase
      was observed among women, while no change was observed among older patients. MI
      severity and case fatality were clearly reduced for both sexes. These data
      suggest that the burden of CHD is shifting from middle-aged men toward middle
      aged women and elderly patients.

PMID- 21859782
TI  - Diet selectivity of juvenile blue crabs (Callinectes sapidus) in Chesapeake Bay.
AB  - Shallow coves in Chesapeake Bay have abundant food and serve as nursery grounds
      for juvenile blue crabs. In this study, we examined the relationships between the
      diet of very small (4-40 mm CW) juvenile blue crabs and the benthic infauna in
      shallow, unvegetated nursery coves. We compared infauna in benthic samples with
      gut contents of juvenile blue crabs from six shallow coves in each of two sub
      estuaries (Rappahannock and York Rivers) in Chesapeake Bay, Virginia, USA.
      Benthic communities differed depending on river and location, with abundant clams
      in upriver regions and abundant polychaetes in downriver regions. Juvenile crabs,
      like adults, appeared to be opportunistic feeders, with gut contents including
      clams, amphipods, polychaetes, small crustaceans, plant matter, and detritus.
      There was a positive relationship between polychaetes in the benthic samples and
      in crab guts, suggesting that juvenile crabs are opportunistic feeders on
      polychaetes in the benthos. Moreover, Ivlev's electivity index and foraging ratio
      showed that clams and polychaetes were selectively eaten at all locations.
      Alternatively, crabs selectively rejected amphipods. Crab densities corresponded
      positively with polychaete densities, which suggests that there may be bottom-up
      control of crab distributions and that food resources are important in nursery
      habitats.

PMID- 21859781
TI  - Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells
      through mitochondrial depolarization and endoplasmic reticulum stress.
AB  - Capsaicin, a pungent compound found in hot chili peppers, has been reported to
      have antitumor activities in many human cancer cell lines, but the induction of
      precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells
      is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced
      apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved
      endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial
      depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1
      phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent
      manner. Capsaicin treatment triggered ER stress by promoting the production of
      reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme
      (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose
      regulated protein 78 (GRP78). Other effects included an increase in cytosolic
      Ca(2+), loss of the mitochondrial transmembrane potential (DeltaPsi(m)), releases
      of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9
      and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and
      abundance of apoptosis-related protein levels. These results suggest that ER
      stress- and mitochondria-mediated cell death is involved in capsaicin-induced
      apoptosis in NPC-TW 039 cells.

PMID- 21859783
TI  - A proposal and prototype for a Research Risk Repository to improve the protection
      of research participants.
AB  - BACKGROUND: Accurate and consistent risk assessment is vital for the protection
      of research participants. Yet, current evaluation of the risks of research
      interventions often does not take into account the relevant empirical data. This
      approach raises concern that current practice may not be protecting research
      participants adequately, or that it may be thwarting acceptable research.
      PURPOSE: To propose and evaluate the possibility of creating and maintaining a
      Research Risk Repository which would make empirical data on the risks of research
      interventions available to institutional review boards, investigators, funders,
      and others. METHODS: Analysis of the usefulness of a Research Risk Repository and
      evaluation of whether currently available empirical data are sufficient to
      establish such a repository. RESULTS: Creation of a Research Risk Repository
      would provide a vital resource for systematically and accurately evaluating the
      risks of biomedical research. Realizing this goal requires data that have at
      least 4 characteristics: (1) trustworthy: to ensure credibility to all
      stakeholders; (2) robust: to support confident risk determinations; (3)
      inclusive: to cover all potential harms of the interventions under review; and
      (4) comprehensive: to determine which factors influence the risks of the
      interventions under review. Evaluation of existing data reveals that they satisfy
      these requirements for only a few research interventions and, even in those
      cases, only to a limited extent. Gaps in the currently available evidence
      highlight the need for systematic collection and maintenance of data on the risks
      posed by research interventions. LIMITATIONS: Creation and maintenance of a
      Research Risk Repository would be costly and require regular updating as new data
      are collected, and new practices and interventions emerge. CONCLUSIONS: A
      Research Risk Repository has the potential to significantly improve the
      consistency and accuracy of the evaluation of research risks. However, currently
      available data are generally insufficient for this purpose. Future collection and
      maintenance of data on the risks posed by research interventions will help to
      ensure that research participants receive appropriate protection and promote
      important research consistent with adequate subject protection.

PMID- 21859784
TI  - Agreement between medical expert assessments in social medicine.
AB  - BACKGROUND AND AIMS: Medical specialists in social medicine play an important
      role in description of work-related health problems of the individual citizen in
      the Municipalities, yet knowledge of the consistency in their medical assessment
      remains poor. However, we expect good agreement between medical specialists'
      descriptions of health and work ability. The present paper aims to evaluate inter
      rater differences between assessments issued by medical specialists in social
      medicine on health-related work ability in patients with musculoskeletal diseases
      and some lighter psychiatric diseases. METHODS: A total of 11 medical specialists
      in social medicine from four departments across Denmark each described eight
      subjects' health and health-related disability upon request from the municipal
      authorities. The resultant 88 written medical expert assessments were evaluated
      and scored independently by two medical specialists in social medicine with
      respect to functional impairment/ health-related work ability as intact, slightly
      reduced, much reduced, or extremely reduced. Kappa analysis described the inter
      rater agreements. RESULTS: The combined Kappa value for work ability was 0.33
      (slight agreement). In the category ''extremely reduced'' work ability the Kappa
      value was 0.61 (good agreement), but mostly this result was due to one subject.
      One department had better intra-departmental agreement than the other
      departments. Agreement on the level of work ability was poorer in subjects with
      psychiatric diseases. CONCLUSIONS: The assessments from medical specialists in
      social medicine on work ability and thereby occupational possibilities show much
      variation. The results of the present study demonstrate that there is much room
      for improving agreement on these assessments.

PMID- 21859785
TI  - Laser fluorescence angiography reveals perfusion defects in retrograde
      cardioplegia.
AB  - BACKGROUND: Adequate perfusion of the right ventricle with retrograde
      cardioplegia has always been questioned. However, clinical studies suggested
      sufficient protection and, up to now, intraoperative assessment of cardioplegia
      distribution has been difficult. METHODS: As a pilot study in 14 patients, we
      used indocyanine green laser fluorescence angiography (ICGLA) to assess vascular
      and myocardial perfusion of different areas of the right anterior ventricular
      wall. Regions of interest were analyzed quantitatively using a new software
      package. RESULTS: ICGLA allowed rapid and reliable visualization of cardioplegic
      flow and distribution. Retrograde cardioplegia revealed perfusion defects in the
      territory of the right anterior cardiac veins when compared to antegrade delivery
      and to areas close to the left anterior descending vein(s), confirmed by
      quantitative analyses of maximal fluorescence intensity. Five patients were
      excluded from quantitative analyses. The learning curve, pitfalls, limitations
      and special image details are described. CONCLUSION: A larger study is necessary
      to examine the relevance of perfusion defects to metabolic changes in affected
      myocytes and to global right ventricular function.

PMID- 21859786
TI  - Successful use of a percutaneous miniaturized extracorporeal life support system
      as a bridge and assistance to left ventricular assist device implantation in a
      patient with severe refractory cardiogenic shock.
AB  - We present a 51-year-old man with cardiogenic shock in whom a percutaneous
      extracorporeal life support system (ECLS) was inserted to restore cardiopulmonary
      stability. After successful stabilization, a left ventricular assist device was
      implanted, using the ECLS without switching to a conventional cardiopulmonary
      bypass system to reduce its side effects.

PMID- 21859787
TI  - Direct oxymetric peripheral tissue perfusion monitoring during open heart surgery
      with the use of cardiopulmonary bypass: preliminary experience.
AB  - BACKGROUND: Regional hypoperfusion has been associated with the development of
      postoperative organ dysfunction in cardiac surgery involving cardiopulmonary
      bypass (CPB). Direct tissue oxymetry is a potentially new method for monitoring
      the quality of the peripheral tissue perfusion during CPB. The aim of this study
      was to assess the effects of CPB in skeletal muscle oxygenation when measured in
      the deltoid muscle by direct oxymetry during perioperative period. METHOD: Seven
      patients underwent on-pump coronary artery bypass grafting. Direct oxymetry was
      performed by an optical cathether introduced into the deltoid muscle. Continuous
      measurement was made during the surgical procedure and the postoperative period.
      Mean arterial blood pressure, blood flow during CPB, laboratory markers of tissue
      hypoperfusion, blood gases and body temperature were also recorded. RESULTS:
      Interstitial muscle tissue oxygen tension (pO(2)) decreased after the
      introduction to anaesthesia and, more significantly, during CPB. After the
      disconnection from CPB at the end of the operation, the pO(2) returned to pre
      anaesthetic values. During the first hours after admission of the patients to the
      intensive care unit, the pO(2) progressively decreased, reached a minimum value
      after four hours, and increased slowly thereafter. There was a significant
      correlation of pO(2) with mean arterial blood pressure and blood flow during that
      time. CONCLUSION: The result of this first measurement seems to demonstrate that
      the standard technique of conducting cardiopulmonary bypass produces low muscle
      oxygen tension and, thus, little perfusion of skeletal muscle. The data also
      indicate that both high mean arterial blood pressure and high flow are necessary
      during CPB to ensure skeletal muscle perfusion. The investigation is continuing.

PMID- 21859788
TI  - Coagulopathy associated with massive cell salvage transfusion following aortic
      surgery.
AB  - Cell saver blood is used within the peri-operative setting of cardiothoracic
      surgery to reduce the need for transfusion of allogenic blood products. Several
      meta-analyses have proven a significant decrease in allogenic transfusion with
      the use of cell salvage techniques. Washing of red cells by the cell saver and
      subsequent transfusion of suspended red cells can occasionally cause
      coagulopathy, particularly when using high concentration heparin saline to wash
      the spilled blood. We present the case of a 74-year-old female who underwent
      complicated aortic surgery and was transfused large volumes of cell-saved blood
      due to post-operative bleeding, which subsequently led to coagulopathy.

PMID- 21859789
TI  - Are minimized perfusion circuits the better heart lung machines? Final results of
      a prospective randomized multicentre study.
AB  - INTRODUCTION: Minimized perfusion circuits (MPCs), although aiming at minimizing
      the adverse effects of cardiopulmonary bypass, have not yet gained popularity.
      This can be attributed to concerns regarding their safety, as well as lack of
      sufficient evidence of their benefit. METHODS: Described is a randomized,
      multicentre study comparing the MPC - ROCsafeRX to standard cardiopulmonary
      bypass in patients undergoing elective coronary artery bypass grafting and/ or
      aortic valve replacement. RESULTS: Five hundred patients were included in the
      study (252 randomized to the ROCsafeRX group and 248 to standard cardiopulmonary
      bypass). Both groups were well matched for demographic characteristics and type
      of surgery. No operative mortality and no device-related complications were
      encountered. Transfusion requirement (333 +/- 603 vs. 587 +/- 1010 ml; p=0.001),
      incidence of atrial fibrillation (16.3% vs. 24.2%; p=0.03) and the incidence of
      major adverse events (9.1% vs. 16.5%; p=0.02) were all in favour of the MPC
      group. CONCLUSION: These results confirm both the safety and efficacy of the
      ROCsafeRX MPC for a large variety of cardiac patients. Minimized perfusion
      circuits should, therefore, play a greater role in daily practice so that as many
      patients as possible can benefit from their advantages.

PMID- 21859791
TI  - Clarification in law is sought after man is jailed for infecting partner with
      genital herpes.

PMID- 21859790
TI  - Zero balance ultrafiltration for the correction of acute acidosis after a period
      of prolonged deep hypothermic circulatory arrest.
AB  - A 36-year-old woman with normal renal function underwent a total arch replacement
      requiring 110 minutes of deep hypothermic circulatory arrest. Prior to rewarming,
      a pH of 7.063 with a base deficit of 10.8 was obtained. Zero-balance
      ultrafiltration (Z-BUF) was initiated during rewarming 7 minutes after resumption
      of cardiopulmonary bypass. After one hour (10L) of Z-BUF, all electrolyte and
      acid-base disturbances were fully corrected. Our case illustrates that Z-BUF
      offers a valuable option for the correction of severe electrolyte and acid-base
      disturbances in adults undergoing cardiac surgery. Its use should be considered
      in addition to the more standard pharmacologic approaches to such derangements as
      it offers rapid and predictable electrolyte and acid-base correction and
      potential anti-inflammatory benefits.

PMID- 21859792
TI  - Functional assessment in older people.

PMID- 21859793
TI  - The future of the primary medical workforce.

PMID- 21859794
TI  - Take dietary truths with a pinch of salt.

PMID- 21859795
TI  - Interaction of a goose-type lysozyme with chitin oligosaccharides as determined
      by NMR spectroscopy.
AB  - The interaction between a goose-type lysozyme from ostrich egg white (OEL) and
      chitin oligosaccharides [(GlcNAc)(n) (n = 2, 4 and 6)] was studied by nuclear
      magnetic resonance (NMR) spectroscopy. A stable isotope-labelled OEL was produced
      in Pichia pastoris, and backbone resonance assignments for the wild-type and an
      inactive mutant (E73A OEL) were achieved using modern multi-dimensional NMR
      techniques. NMR titration was performed with (GlcNAc)(n) for mapping the
      interaction sites of the individual oligosaccharides based on the shifts in the
      two-dimensional heteronuclear single quantum correlation (HSQC) resonances. In
      wild-type OEL, the interaction sites for (GlcNAc)(n) were basically similar to
      those determined by X-ray crystallography. In E73A OEL, however, the interaction
      sites were spread more widely over the substrate-binding cleft than expected, due
      to the multiple modes of binding. The association constant for E73A OEL and
      (GlcNAc)(6) calculated from the shifts in the Asp97 resonance (7.2 * 10(3) M(-1))
      was comparable with that obtained by isothermal titration calorimetry (5.3 *
      10(3) M(-1)). The interaction was enthalpy-driven as judged from the
      thermodynamic parameters (DeltaH = -6.1 kcal/mol and TDeltaS = -1.0 kcal/mol).
      This study provided novel insights into the oligosaccharide binding mechanism and
      the catalytic residues of the enzymes belonging to family GH-23.

PMID- 21859797
TI  - Sex and diabetes: a thematic analysis of gay and bisexual men's accounts.
AB  - Around 50 per cent of men with diabetes experience erectile dysfunction. Much of
      the literature focuses on quality of life measures with heterosexual men in
      monogamous relationships. This study explores gay and bisexual men's experiences
      of sex and diabetes. Thirteen interviews were analysed and three themes
      identified: erectile problems; other 'physical' problems; and disclosing diabetes
      to sexual partners. Findings highlight a range of sexual problems experienced by
      non-heterosexual men and the significance of the cultural and relational context
      in which they are situated. The personalized care promised by the UK government
      should acknowledge the diversity of sexual practices which might be affected by
      diabetes.

PMID- 21859796
TI  - The Class D beta-lactamase family: residues governing the maintenance and
      diversity of function.
AB  - Class D beta-lactamases, a major source of bacterial resistance to beta-lactam
      antibiotic therapies, represent a distinct subset of the beta-lactamase
      superfamily. They share a serine hydrolase mechanism with Classes A/C vs. Class
      B. Further understanding of their sequence-structure-function relationships would
      benefit efforts to design a new generation of antibiotics as well as to predict
      evolutionary mechanisms in response to such therapies. Here we describe analyses
      based on our high-resolution multiple sequence alignment and phylogenetic tree of
      ~80 Class D beta-lactamases that leverage several 3D structures of these enzymes.
      We observe several sequence clusters on the phylogenetic tree, some that are
      species specific while others include several species from alpha-, beta- and
      gamma-proteobacteria. Residues characteristic of a specific cluster were
      identified and shown to be located just outside the active site, possibly
      modulating the function of the catalytic residues to facilitate reactions with
      specific types of beta-lactams. Most significant was the discovery of a likely
      disulfide bond in a large group composed of alpha-, beta- and gamma
      proteobacteria that would contribute to enzyme stability and hence bacterial
      viability under antibiotic assault. A network of co-evolving residues was
      identified which suggested the importance of maintaining a surface for binding a
      highly conserved Phe69.

PMID- 21859798
TI  - Development of a scale to measure African American attitudes toward organ
      donation.
AB  - African American attitudes toward organ donation differ from other racial and
      ethnic groups. However, existing measures of organ donation attitudes do not
      adequately address ethnic identity and cultural factors. We examined the
      psychometric properties of a new 18-item organ donation scale among 1225 members
      of 21 African American churches in Southeast Michigan. We identified three
      factors: (1) Barriers; (2) Family/Race Benefits; and (3) Altruism. More positive
      donation attitudes on each subscale were observed for individuals who reported
      being enrolled as a donor. Among individuals not enrolled, higher scores were
      observed on scales two and three for those with stronger intentions to enroll.

PMID- 21859799
TI  - Illness perception in bulimia nervosa.
AB  - The study was designed to extend our understanding of illness perceptions in
      patients with bulimia nervosa (BN). Seventy-eight participants with BN or BN-type
      Eating Disorder Not Otherwise Specified (EDNOS-BN) completed the Revised Illness
      Perception Questionnaire (IPQ-R) (Moss-Morris et al., 2002). Clinical variables
      were also assessed. Participants experienced their ED as chronic, with serious
      consequences and high associated levels of anxiety and depression. The disorder
      was attributed primarily to psychological causes. The results indicate the
      perceived severity of BN, and high level of associated distress. These findings
      highlight the potential for targeting illness perceptions in treatment.

PMID- 21859800
TI  - Are nature lovers happy? On various indicators of well-being and connectedness
      with nature.
AB  - Connectedness with nature (CN) is seen as a personal disposition relevant for
      environmental as well as human health. In five questionnaire studies (N = 547) we
      systematically investigated the relationship between various operationalizations
      of well-being and CN. CN was assessed with two different tools in parallel. All
      significant correlations were controlled for the effects of age and gender.
      Psychological well-being, meaningfulness and vitality were found to be robustly
      correlated with CN. We highlight the relevance of CN with respect to human health
      and further discuss conceptual differences unraveled by the concurrent
      application of two CN-tools.

PMID- 21859802
TI  - Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers.
AB  - Estrogens and androgens are instrumental in the maturation of many hormone
      dependent cancers. Consequently, the enzymes involved in their synthesis are
      cancer therapy targets. One such enzyme, steroid sulfatase (STS), hydrolyses
      estrone sulfate, and dehydroepiandrosterone sulfate to estrone and
      dehydroepiandrosterone respectively. These are the precursors to the formation of
      biologically active estradiol and androstenediol. This review focuses on three
      aspects of STS inhibitors: 1) chemical development, 2) biological activity, and
      3) clinical trials. The aim is to discuss the importance of estrogens and
      androgens in many cancers, the developmental history of STS inhibitor synthesis,
      the potency of these compounds in vitro and in vivo and where we currently stand
      in regards to clinical trials for these drugs. STS inhibitors are likely to play
      an important future role in the treatment of hormone-dependent cancers. Novel in
      vivo models have been developed that allow pre-clinical testing of inhibitors and
      the identification of lead clinical candidates. Phase I/II clinical trials in
      postmenopausal women with breast cancer have been completed and other trials in
      patients with hormone-dependent prostate and endometrial cancer are currently
      active. Potent STS inhibitors should become therapeutically valuable in hormone
      dependent cancers and other non-oncological conditions.

PMID- 21859803
TI  - Genetic architecture of growth traits revealed by global epistatic interactions.
AB  - Epistasis has long been recognized as fundamentally important in understanding
      the structure, function, and evolutionary dynamics of biological systems. Yet,
      little is known about how it is distributed underlying specific traits. Based on
      a global map of epistatic interactions in baker's yeast, Saccharomyces
      cerevisiae, we show that epistasis is prevalent (~13% increase from random
      expectation) and displays modular architecture among genes that underlie the same
      growth traits. More interestingly, our results indicate that hub genes
      responsible for the same growth traits tend to link epistatically with each other
      more frequently than random expectation. Our results provide a genome-wide
      perspective on the genetic architecture of growth traits in a eukaryotic
      organism.

PMID- 21859801
TI  - Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic
      links to arrhythmogenic right ventricular cardiomyopathy.
AB  - BACKGROUND: Immunoreactive signal for the desmosomal protein plakoglobin (gamma
      catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic
      right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused
      by mutations in genes encoding desmosomal proteins. Previously, we observed a
      false-positive case in which plakoglobin signal was reduced in a patient
      initially believed to have ARVC but who actually had cardiac sarcoidosis.
      Sarcoidosis can masquerade clinically as ARVC but has not been previously
      associated with altered desmosomal proteins. METHODS AND RESULTS: We observed
      marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte
      junctions in patients with sarcoidosis and giant cell myocarditis, both highly
      arrhythmogenic forms of myocarditis associated with granulomatous inflammation.
      In contrast, plakoglobin signal was not depressed in lymphocytic
      (nongranulomatous) myocarditis. To determine whether cytokines might promote
      dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat
      ventricular myocytes with selected inflammatory mediators. Brief exposure to low
      concentrations of interleukin (IL)-17, tumor necrosis factor-alpha (TNF-alpha),
      and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation
      of plakoglobin from cell-cell junctions to intracellular sites, whereas other
      potent cytokines implicated in nongranulomatous myocarditis had no effect, even
      at much higher concentrations. We also observed myocardial expression of IL-17
      and TNF-alpha and elevated levels of serum inflammatory mediators, including IL
      6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein
      1beta, in patients with ARVC (all P<0.0001 compared with controls). CONCLUSIONS:
      The results suggest novel disease mechanisms involving desmosomal proteins in
      granulomatous myocarditis and implicate cytokines, perhaps derived in part from
      the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in
      ARVC.

PMID- 21859804
TI  - Detecting past positive selection through ongoing negative selection.
AB  - Detecting positive selection is a challenging task. We propose a method for
      detecting past positive selection through ongoing negative selection, based on
      comparison of the parameters of intraspecies polymorphism at functionally
      important and selectively neutral sites where a nucleotide substitution of the
      same kind occurred recently. Reduced occurrence of recently replaced ancestral
      alleles at functionally important sites indicates that negative selection
      currently acts against these alleles and, therefore, that their replacements were
      driven by positive selection. Application of this method to the Drosophila
      melanogaster lineage shows that the fraction of adaptive amino acid replacements
      remained approximately 0.5 for a long time. In the Homo sapiens lineage, however,
      this fraction drops from approximately 0.5 before the Ponginae-Homininae
      divergence to approximately 0 after it. The proposed method is based on
      essentially the same data as the McDonald-Kreitman test but is free from some of
      its limitations, which may open new opportunities, especially when many genotypes
      within a species are known.

PMID- 21859805
TI  - Comparative analysis of chromosome counts infers three paleopolyploidies in the
      mollusca.
AB  - The study of paleopolyploidies requires the comparison of multiple whole genome
      sequences. If the branches of a phylogeny on which a whole-genome duplication
      (WGD) occurred could be identified before genome sequencing, taxa could be
      selected that provided a better assessment of that genome duplication. Here, we
      describe a likelihood model in which the number of chromosomes in a genome
      evolves according to a Markov process with one rate of chromosome duplication and
      loss that is proportional to the number of chromosomes in the genome and another
      stochastic rate at which every chromosome in the genome could duplicate in a
      single event. We compare the maximum likelihoods of a model in which the genome
      duplication rate varies to one in which it is fixed at zero using the Akaike
      information criterion, to determine if a model with WGDs is a good fit for the
      data. Once it has been determined that the data does fit the WGD model, we infer
      the phylogenetic position of paleopolyploidies by calculating the posterior
      probability that a WGD occurred on each branch of the taxon tree. Here, we apply
      this model to a molluscan tree represented by 124 taxa and infer three putative
      WGD events. In the Gastropoda, we identify a single branch within the
      Hypsogastropoda and one of two branches at the base of the Stylommatophora. We
      also identify one or two branches near the base of the Cephalopoda.

PMID- 21859806
TI  - Evolution of the Max and Mlx networks in animals.
AB  - Transcription factors (TFs) are essential for the regulation of gene expression
      and often form emergent complexes to perform vital roles in cellular processes.
      In this paper, we focus on the parallel Max and Mlx networks of TFs because of
      their critical involvement in cell cycle regulation, proliferation, growth,
      metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain
      mediates the competitive protein dimerization and DNA binding among Max and Mlx
      network members to form a complex system of cell regulation. To understand the
      importance of these network interactions, we identified the bHLHZ domain of Max
      and Mlx network proteins across the animal kingdom and carried out several
      multivariate statistical analyses. The presence and conservation of Max and Mlx
      network proteins in animal lineages stemming from the divergence of Metazoa
      indicate that these networks have ancient and essential functions. Phylogenetic
      analysis of the bHLHZ domain identified clear relationships among protein
      families with distinct points of radiation and divergence. Multivariate
      discriminant analysis further isolated specific amino acid changes within the
      bHLHZ domain that classify proteins, families, and network configurations. These
      analyses on Max and Mlx network members provide a model for characterizing the
      evolution of TFs involved in essential networks.

PMID- 21859808
TI  - The evolving role of preoperative testing in vascular surgery patients: can a
      little knowledge be dangerous?
AB  - It has been traditionally recommended that candidates for vascular surgery
      receive noninvasive stress perfusion testing risk stratification to help decide
      which patients may benefit from coronary artery revascularization. Recent
      clinical trials have contested the efficacy of revascularization in this
      population as well as the information yield of noninvasive testing. This article
      reviews a number of these studies that are likely to change our beliefs regarding
      testing and subsequent interventions as well as evolving role of medical therapy
      in patients undergoing vascular surgery.

PMID- 21859807
TI  - Evolutionary patterns of recently emerged animal duplogs.
AB  - Duplogs, or intraspecies paralogs, constitute the important portion of eukaryote
      genomes and serve as a major source of functional innovation. We conducted
      detailed analyses of recently emerged animal duplogs. Genome data of three
      vertebrate species (Homo sapiens, Mus musculus, and Danio rerio), Caenorhabditis
      elegans, and two Drosophila species (Drosophila melanogaster and D.
      pseudoobscura) were used. Duplication events were divided into six age-groups
      according to the synonymous distance (dS) up to 0.6. Duplogs were classified into
      four equal-sized classes on physical distances and into three classes on relative
      orientations. We observed the following shared characteristics among
      intrachromosomal multiexon duplogs: 1) inverted duplogs account for 20-50%, and
      about a half of the physically most distant 25%; 2) except for C. elegans, the
      composition of physical distances, that of relative orientations, and the
      proportion of inverted duplogs in each physical distance category are more or
      less uniform; 3) except for C. elegans, the characteristics of the youngest (dS <
      0.01) duplogs are similar to the overall characteristics of the entire set. These
      results suggest that intrachromosomal duplogs with fairly long physical distances
      were generated at once, rather than resulting from tandem duplications and
      subsequent genomic rearrangements. This is different from the three well-known
      modes of gene duplication: tandem duplication, retrotransposition, and genome
      duplication. We termed this new mode as "drift" duplication. The drift
      duplication has been producing duplicate copies at paces comparable with tandem
      duplications since the common ancestor of vertebrates, and it may have already
      operated in the common ancestor of bilateral animals.

PMID- 21859809
TI  - Monocyte chemoattractant protein-1 induces endothelial cell apoptosis in vitro
      through a p53-dependent mitochondrial pathway.
AB  - The cystine-cystine (CC) chemokine monocyte chemoattractant protein-1 (MCP-1) has
      been established playing a pathogenic role in the development of atherosclerosis
      due to its chemotactic ability of leading monocytes to locate to subendothelia.
      Recent studies have revealed more MCP-1 functions other than chemotaxis. Here we
      reported that various concentrations (0.1-100 ng/ml) of MCP-1 induced human
      umbilical vein endothelial cell (HUVEC) strain CRL-1730 apoptosis, caspase-9
      activation, and a couple of mitochondrial alterations. Moreover, MCP-1
      upregulated p53 expression of HUVECs and the p53-specific inhibitor pifithrin
      alpha (PFTalpha) rescued the MCP-1-induced apoptosis of HUVECs. Furthermore, PKC
      (protein kinase C) activation or inhibition might also affect HUVECs apoptosis
      induced by MCP-1. These findings together demonstrate that MCP-1 exerts direct
      proapoptotic effects on HUVECs in vitro via a p53-dependent mitochondrial
      pathway.

PMID- 21859810
TI  - Primary care providers advising smokers to quit: comparing effectiveness between
      those with and without alcohol, drug, or mental disorders.
AB  - INTRODUCTION: Individuals with alcohol, drug, or mental (ADM) disorders combined
      make up over 40% of all smokers in the U.S. Primary care providers (PCPs) play an
      important role in smoking cessation counseling, but their effectiveness with this
      population is unclear. This study evaluated the effectiveness of PCP smoking
      cessation counseling for smokers with ADM disorders. METHODS: Probit regressions
      conducted in 2009-2010 examined the relationship between past year PCP smoking
      cessation counseling and successful quitting among 1,356 adults who reported
      smoking in the 1998-1999 Community Tracking Study survey and who reported seeing
      a PCP in the past year in the follow-up 2000-2001 Healthcare for Communities
      Survey. Past year PCP exercise counseling was used as an instrumental variable
      for past year PCP smoking cessation counseling to account for potential hidden
      bias between smoking status and receipt of smoking cessation counseling. RESULTS:
      Smokers with and without ADM disorders were equally likely to receive smoking
      cessation counseling (72.9% vs. 69.9%). Using the instrumental variable approach,
      smoking cessation counseling by PCPs was significantly associated (p < .01) with
      quitting among both groups. Predicted probabilities of quitting without smoking
      cessation counseling were 6.0% for smokers with ADM disorders and 10.5% for
      smokers without ADM disorders. Predicted probabilities of quitting with smoking
      cessation counseling were 31.3% for smokers with ADM disorders and 34.9% for
      smokers without ADM disorders. CONCLUSIONS: This study shows that PCPs can help
      smokers with ADM disorders successfully quit. These smokers should be targeted
      for smoking cessation counseling to reduce the health burden of tobacco.

PMID- 21859811
TI  - Assessment of PET tracer uptake in hormone-independent and hormone-dependent
      xenograft prostate cancer mouse models.
AB  - The pharmacokinetics of (18)F-fluorodeoxythymidine (FLT), (18)F-FDG, (11)C
      choline, and (18)F-fluoroethylcholine (FEC) in 2 hormone-independent (PC-3,
      DU145) and 2 hormone-dependent (CWR22, PAC120) prostate cancer xenograft mouse
      models were evaluated by PET and compared by immunohistochemistry. Further
      investigation was performed to determine whether PET can detect early changes in
      tumor metabolism after androgen ablation therapy through surgical castration.
      METHODS: PET was performed on 4 consecutive days. In addition, the CWR22 and
      PAC120 tumor models were surgically castrated after the baseline measurement and
      imaged again after castration. The tracer uptake was analyzed using time-activity
      curves, percentage injected dose per volume (%ID/cm(3)), and tumor-to-muscle
      ratio (T/M). RESULTS: Regarding the hormone-independent prostate tumor models,
      (18)F-FLT showed the best T/M and highest %ID/cm(3) in PC-3 (2.97 +/- 0.63
      %ID/cm(3)) and DU145 (2.06 +/- 0.75 %ID/cm(3)) tumors. (18)F-FDG seemed to be the
      tracer of choice for delineation of the PC-3 tumors but not for the DU145 tumors.
      Using (11)C-choline (PC-3: 1.33 +/- 0.29 %ID/cm(3), DU145: 1.60 +/- 0.27
      %ID/cm(3)) and (18)F-FEC, we did not find any significant uptake in the tumors,
      compared with muscle tissue. Regarding the hormone-dependent prostate tumor
      models, the CWR22 model showed a highly significant (P < 0.01) decrease in tumor
      (18)F-FDG uptake from 4.11 +/- 1.29 %ID/cm(3) to 2.19 +/- 1.45 %ID/cm(3) after
      androgen ablation therapy. However, the (18)F-FLT, (11)C-choline, or (18)F-FEC
      tracers did not provide sufficient uptake or reliable information about therapy
      response in CWR22 tumors. The PAC120 model showed a significant increase in (18)F
      FLT tumor uptake (P = 0.015) after androgen ablation therapy. The accumulation of
      (18)F-FEC (before: 2.32 +/- 1.01 %ID/cm(3), after: 1.36 +/- 0.39 %ID/cm(3)) was
      found to be the next highest after (18)F-FDG (before: 2.45 +/- 0.93 %ID/cm(3),
      after: 2.18 +/- 0.65 %ID/cm(3)) in PAC120 tumors before castration and is better
      suited for monitoring therapy response. CONCLUSION: This comprehensive study in 2
      hormone-dependent and 2 hormone-independent prostate tumor mouse models shows
      that (18)F-FLT and (18)F-FDG are the most appropriate tracers for delineation of
      PC-3, DU145 (except (18)F-FDG), and CWR22 tumors, but not for PAC120 tumors.
      (18)F-FEC and (11)C-choline, in particular, revealed insufficient T/M ratio in
      the prostate tumor models. The results may indicate that radiolabeled choline and
      choline derivatives compete with a high concentration of the precursor
      dimethylaminoethanol, resulting in reduced uptake in small-rodent tumor models, a
      hypothesis that is currently under investigation in our laboratory.

PMID- 21859812
TI  - Genetic and molecular analysis of a new unbalanced X;18 rearrangement:
      localization of the diminished ovarian reserve disease locus in the distal Xq
      POF1 region.
AB  - BACKGROUND: Diminished ovarian reserve (DOR) is a heterogeneous disorder causing
      infertility, characterized by a decreased number of oocytes, the genetic cause of
      which is still unknown. METHODS AND RESULTS: We describe a family with a new
      unbalanced X;18 translocation der(X) associated with either fully attenuated or
      DOR phenotype in the same family. Cytogenetics and array comparative genomic
      hybridization (aCGH) studies have revealed the same partial Xq monosomy and
      partial 18q trisomy in both the 32-year-old female with DOR and the unaffected
      mother. The genetic analysis has defined a subtelomeric deletion spanning 13.3 Mb
      from Xq27.3 to -Xqter, which covers the premature ovarian failure locus 1 (POF1);
      and a duplication spanning 13.4 Mb, from 18q22.1 to 18qter. From a parental
      origin study, we have inferred that the rearranged X chromosome is maternally
      derived. The Xq27 and 18q22 breakpoint regions fall in a region extremely rich in
      long interspersed nuclear element, a class of retrotransposons able to trigger
      mispairing and unusual crossovers. X-inactivation studies reveal a skewing of
      der(X) both in the mother and the proband. Therefore, the phenotypic expression
      of der(X) is fully attenuated in the fertile mother and partially attenuated in
      the DOR daughter. CONCLUSIONS: We report on an unbalanced maternally derived
      translocation (X;18)(q27;q22) with different intra-familial reproductive
      performances, ranging from fertility to DOR. Skewed X-inactivation seems to
      restore the unbalanced genetic make-up, fully silencing the 18q22 trisomy and at
      least in part the Xq27 monosomy. The chromosomal abnormality observed in this
      family supports the presence of a DOR susceptibility locus in the distal Xq
      region and targets the POF1 region for further investigation.

PMID- 21859813
TI  - Medical injury, patients' claims and the effects of government responses in Anglo
      American legal systems.

PMID- 21859814
TI  - Remedies sought and obtained in healthcare complaints.
AB  - In the wake of adverse events, injured patients and their families have a complex
      range of needs and wants. The tort system, even when operating at its best, will
      inevitably fall far short of addressing them. In Australia and New Zealand,
      government-run health complaints commissions take a more flexible and expansive
      approach to providing remedies for patients injured by or disgruntled with care.
      Unfortunately, survey research has shown that many patients in these systems are
      dissatisfied with their experience. We hypothesised that an important explanation
      for this dissatisfaction is an 'expectations gap'; discordance between what
      complainants want and what they eventually get out of the process. Analysing a
      sample of complaints relating to informed consent from the Commission in Victoria
      (Australia's second largest state, with 5.2 million residents), we found evidence
      of such a gap. One-third (59/189) of complainants who sought restoration received
      it; 1 in 5 complainants (17/101) who sought correction received assurances that
      changes had been or would be made to reduce the risk of others suffering a
      similar harm; and fewer than 1 in 10 (3/37) who sought sanctions saw steps taken
      to achieve this outcome initiated. We argue that bridging the expectations gap
      would go far toward improving patient satisfaction with complaints systems, and
      suggest several ways this might be done.

PMID- 21859815
TI  - Wide dissemination of multidrug-resistant Shigella isolates in China.
AB  - OBJECTIVES: To evaluate the prevalence of antimicrobial resistance and selected
      antimicrobial resistance mechanisms in Shigella isolates recovered in outpatients
      from 1997 to 2009 in China. METHODS: The isolates were subjected to serotyping
      and antimicrobial susceptibility testing. Shigella isolates producing extended
      spectrum beta-lactamases (ESBLs) or resistance to ciprofloxacin were further
      characterized by PFGE to determine the genetic relatedness. These isolates were
      also screened for beta-lactamase genes and mutations in the quinolone resistance
      determining regions (QRDRs) by PCR. DNA sequence analysis was also performed.
      RESULTS: After serotyping, 301 Shigella isolates were grouped into three
      subgroups and 13 distinct serotypes. The antimicrobial resistance profiles
      differed among subgroups and serotypes. Ciprofloxacin-resistant isolates were
      mainly Shigella flexneri serotypes f2a and f4a, which were resistant to at least
      four additional non-quinolone antimicrobials. Three point mutations in the QRDRs
      of gyrA and parC were identified in all 30 ciprofloxacin-resistant S. flexneri
      isolates. Plasmid-mediated bla(CMY-2), bla(CTX-M-14), bla(CTX-M-15) and bla(CTX-M
      55)-like genes were found in 29 ESBL-producing isolates and three clavulanic-acid
      resistant isolates, and six isolates also exhibited resistance to ciprofloxacin.
      Distinct genetic differences in both serotypes and PFGE profiles were observed
      for these ciprofloxacin- or extended-spectrum-cephalosporin-resistant isolates.
      CONCLUSIONS: ESBL-producing or fluoroquinolone-resistant Shigella is no longer an
      unusual phenomenon in the local community. The monitoring programme in China
      should stay vigilant to the dissemination of these isolates and the health
      agencies must take appropriate measures to restrict the abuse of antimicrobials,
      especially in the community.

PMID- 21859816
TI  - NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of
      glucose metabolism but requires SGLT1.
AB  - AIMS: Exposure to high glucose (HG) stimulates reactive oxygen species (ROS)
      production by NADPH oxidase in cardiomyocytes, but the underlying mechanism
      remains elusive. In this study, we have dissected the link between glucose
      transport and metabolism and NADPH oxidase activation under hyperglycaemic
      conditions. METHODS AND RESULTS: Primary cultures of adult rat cardiomyocytes
      were exposed to HG concentration (HG, 21 mM) and compared with the normal glucose
      level (LG, 5 mM). HG exposure activated Rac1GTP and induced p47phox translocation
      to the plasma membrane, resulting in NADPH oxidase (NOX2) activation, increased
      ROS production, insulin resistance, and eventually cell death. Comparison of the
      level of O-linked N-acetylglucosamine (O-GlcNAc) residues in LG- and HG-treated
      cells did not reveal any significant difference. Inhibition of the pentose
      phosphate pathway (PPP) by 6-aminonicotinamide counteracted ROS production in
      response to HG but did not prevent Rac-1 upregulation and p47phox translocation
      leading to NOX2 activation. Modulation of glucose uptake barely affected
      oxidative stress and toxicity induced by HG. More interestingly, non
      metabolizable glucose analogues (i.e. 3-O-methyl-D-glucopyranoside and alpha
      methyl-D-glucopyranoside) reproduced the toxic effect of HG. Inhibition of the
      sodium/glucose cotransporter SGLT1 by phlorizin counteracted HG-induced NOX2
      activation and ROS production. CONCLUSION: Increased glucose metabolism by itself
      does not trigger NADPH oxidase activation, although PPP is required to provide
      NOX2 with NADPH and to produce ROS. NOX2 activation results from glucose
      transport through SGLT1, suggesting that an extracellular metabolic signal
      transduces into an intracellular ionic signal.

PMID- 21859817
TI  - Monomeric C-reactive protein is prothrombotic and dissociates from circulating
      pentameric C-reactive protein on adhered activated platelets under flow.
AB  - AIMS: We previously reported that C-reactive protein bioactivity on
      thrombogenesis was based on loss of its pentameric symmetry, resulting in
      formation of monomeric C-reactive protein. Our purpose was to provide mechanistic
      information on the direct effects of C-reactive protein isoforms on platelet
      activation and provide a C-reactive protein dissociation mechanism in circulating
      blood. METHODS AND RESULTS: C-reactive protein-induced platelet activation was
      evaluated by flow cytometry. Platelet aggregation, clot properties, and
      coagulation were also measured. Washed platelets were incubated with C-reactive
      protein isoforms and vasodilator-stimulated phosphoprotein (VASP) phosphorylation
      was analysed by western blot and immunofluorescence. C-reactive protein
      dissociation under flow was evaluated by confocal microscopy on the surface of
      adhered platelets after perfusing human blood containing pentameric C-reactive
      protein at different shear rates. Dissociated monomeric C-reactive protein
      thrombogenicity was measured in flow experiments. Platelet aggregation and flow
      cytometry analysis revealed that monomeric C-reactive protein significantly
      induced platelet aggregation, surface P-selectin and CD63 exposure, and
      glycoprotein IIb-IIIa activation, whereas pentameric C-reactive protein was
      unable to produce any effect. p38 mitogen-activated protein kinase (MAPK) and Jun
      N-terminal kinase (JNK) inhibitors, as well as CD36 blocking antibody partially
      inhibited monomeric C-reactive protein-induced platelet activation and
      aggregation. Additionally, monomeric C-reactive protein significantly induced
      VASP dephosphorylation at serine 239. We found that pentameric C-reactive protein
      dissociated into monomeric C-reactive protein on the surface of activated adhered
      platelets under flow conditions and that this generated monomeric C-reactive
      protein promoted further platelet recruitment. CONCLUSIONS: These data indicate
      that whereas serum pentameric C-reactive protein may not affect platelet
      activation, monomeric C-reactive protein, which dissociates from pentameric C
      reactive protein on the surface of activated platelets, could contribute to
      atherothrombotic complications by promoting thrombosis.

PMID- 21859818
TI  - Ultrasound molecular imaging of angiogenesis induced by mutant forms of hypoxia
      inducible factor-1alpha.
AB  - AIMS: Targeted point mutants of hypoxia-inducible factor-1alpha (HIF-1alpha) are
      potential optimal agents for angiogenesis therapy. Data are limited regarding the
      angiogenic response of HIF-1alpha mutants. We aimed to compare the angiogenic
      effect of wild-type and mutant HIF-1alpha by contrast ultrasound molecular
      imaging (UMI) of alpha(v)-integrin expression. METHODS AND RESULTS: The wild-type
      gene of human HIF-1alpha, a gene with double mutations (HIF-1alpha(564/803)), a
      gene with triple mutations (HIF-1alpha(564/803/402)), or the LacZ gene (control)
      was transfected into the ischaemic hind limbs of C57BL/6 mice using an adenovirus
      vector. The video intensity of microbubbles targeted to alpha(v)-integrins in the
      ischaemic limbs increased along with the number of point mutations of HIF-1alpha.
      Immunohistochemical expression of endothelial alpha(v)-integrins was higher in
      the mutant HIF-1alpha(564/803/402) group than the other groups as was the density
      of both capillaries and arterioles in ischaemic muscle. Expression of both the
      mRNA and protein for HIF-1alpha and VEGF was significantly higher in the mutant
      HIF-1alpha(564/803/402) group than in the other groups. The half-life of HIF
      1alpha and VEGF mRNA was longer in HIF-1alpha mutant-transfected cells than in
      wild-type HIF-1alpha or LacZ-transfected cells. CONCLUSION: HIF-1alpha mutants
      were more effective for enhancing angiogenesis in ischaemic muscle tissue than
      wild-type HIF-1alpha, and the response could be qualitatively evaluated by UMI of
      alpha(v)-integrins expression.

PMID- 21859819
TI  - Pulmonary hypertension in adult Alk1 heterozygous mice due to oxidative stress.
AB  - AIMS: Mutations in the ALK1 gene, coding for an endothelial-specific receptor of
      the transforming growth factor-beta superfamily, are the underlying cause of
      hereditary haemorrhagic telangiectasia type 2, but are also associated with
      familial pulmonary hypertension (PH). We assessed the lung vasculature of mice
      with a heterozygous deletion of Alk1 (Alk1(+/-)) for disease manifestations and
      levels of reactive O(2) species (ROS) implicated in both disorders. METHODS AND
      RESULTS: Several signs of PH, including elevated right ventricular (RV) systolic
      pressure leading to RV hypertrophy, reduced vascular density, and increased
      thickness and outward remodelling of pulmonary arterioles, were observed in 8- to
      18-week-old Alk1(+/-) mice relative to wild-type littermate controls. Higher ROS
      lung levels were also documented. At 3 weeks, Alk1(+/-) mice were
      indistinguishable from controls and were prevented from subsequently developing
      PH when treated with the anti-oxidant Tempol for 6 weeks, confirming a role for
      ROS in pathogenesis. Levels of NADPH oxidases and superoxide dismutases were
      higher in adults than newborns, but unchanged in Alk1(+/-) mice vs. controls.
      Prostaglandin metabolites were also normal in adult Alk1(+/-) lungs. In contrast,
      NO production was reduced, while endothelial NO synthase (eNOS)-dependent ROS
      production was increased in adult Alk1(+/-) mice. Pulmonary near resistance
      arteries from adult Alk1(+/-) mice showed less agonist-induced force and greater
      acetylcholine-induced relaxation; the later was normalized by catalase or Tempol
      treatment. CONCLUSION: The increased pulmonary vascular remodelling in Alk1(+/-)
      mice leads to signs of PH and is associated with eNOS-dependent ROS production,
      which is preventable by anti-oxidant treatment.

PMID- 21859820
TI  - Simplified prognostic model in patients with oxaliplatin-based or irinotecan
      based first-line chemotherapy for metastatic colorectal cancer: a GERCOR study.
AB  - BACKGROUND: The present study was done to establish a prognostic model for
      patients and trials using an oxaliplatin-based or irinotecan-based first-line
      chemotherapy in metastatic colorectal cancer. PATIENTS AND METHODS: Eight hundred
      three patients treated with FOLFOX or FOLFIRI in three prospective trials were
      randomly separated into learning (n = 535) and validation (n = 268) samples.
      Eleven baseline variables were evaluated in univariate and multivariate analysis
      as prognostic factors for overall survival, and a prognostic score was developed.
      RESULTS: Independent prognostic factors identified in multivariate analysis for
      overall survival were performance status (PS) (p < .001), serum lactate
      dehydrogenase (LDH) (p < .001), and number of metastatic sites (p = .005). A
      prognostic score based on these three variables was found efficient (Harrell's C
      index 0.61). This new model was improved by selecting only PS and LDH (Harrell's
      C index 0.64). Three risk groups for death could be identified: a low-risk group
      (n = 184; median overall survival [OS] 29.8 months), an intermediate-risk group
      (n = 223; median OS 19.5 months), and a high-risk group (n = 128; median OS 13.9
      months). Median survival for the low-, intermediate-, and high-risk groups were
      26.8, 21.1, and 16.5 months, respectively, in the validation sample (Harrell's C
      index 0.63). CONCLUSIONS: Serum LDH level was the main prognostic factor in
      predicting survival, followed by WHO PS. We identified three risk groups for
      death depending on these two baseline parameters. This simple prognostic model
      can be useful for clinician's use and patient stratification in future clinical
      trials.

PMID- 21859821
TI  - Outcomes of research biopsies in phase I clinical trials: the MD anderson cancer
      center experience.
AB  - BACKGROUND: Research biopsies are crucial for exploring the impact of novel
      agents on putative targets. The current study assesses the safety and success
      rate associated with performing such biopsies. METHODS: We reviewed the medical
      records of 155 consecutive patients who had one or more research biopsies as part
      of a phase I trial from September 2004 to October 2009. RESULTS: Of 281 research
      biopsies performed, 118 were paired before and after treatment biopsies (total =
      236 biopsies). The most common sites of biopsy were superficial lymph node
      (19.9%), followed by liver (16.4%), and then soft tissue (15.7%). Ultrasound
      guided biopsies were the most frequent type (53.7%). Among 142 patients who
      consented for mandatory biopsy, 86.6% had the biopsy performed, compared with
      4.4% of 911 patients offered a biopsy on an optional basis (p < .0001). Biopsy
      was obtained most frequently on industry-sponsored trials; lack of funding on
      nonindustry trials was the most common reason that biopsies were not obtained. Of
      281 single biopsies, only 4 (1.4%) had complications: pneumothorax requiring
      chest tube placement (n = 2), infection requiring admission (n = 1), and
      arrhythmia with hypotension (n = 1). All but one biopsy was successful in
      obtaining tissue. No deaths were attributable to biopsy. CONCLUSIONS: Our
      experience demonstrates that research biopsies in early phase clinical trials are
      safe (1.4% risk of serious complications), and a higher percentage of patients
      underwent mandatory biopsies (86.6%) compared with that of the patients with
      optional biopsies (4.4%).

PMID- 21859822
TI  - Judging an unfamiliar object's distance from its retinal image size.
AB  - How do we know how far an object is? If an object's size is known, its retinal
      image size can be used to judge its distance. To some extent, the retinal image
      size of an unfamiliar object can also be used to judge its distance, because some
      object sizes are more likely than others. To examine whether assumptions about
      object size are used to judge distance, we had subjects indicate the distance of
      virtual cubes in complete darkness. In separate sessions, the simulated cube size
      either varied slightly or considerably across presentations. Most subjects
      indicated a further distance when the simulated cube was smaller, showing that
      they used retinal image size to judge distance. The cube size that was considered
      to be most likely depended on the simulated cubes on previous trials. Moreover,
      subjects relied twice as strongly on retinal image size when the range of
      simulated cube sizes was small. We conclude that the variability in the perceived
      cube sizes on previous trials influences the range of sizes that are considered
      to be likely.

PMID- 21859823
TI  - Cannabinoids attenuate hippocampal gamma oscillations by suppressing excitatory
      synaptic input onto CA3 pyramidal neurons and fast spiking basket cells.
AB  - CB(1) cannabinoid receptor (CB(1)R) activation by exogenous ligands can impair
      memory processes, which critically depend on synchronous neuronal activities that
      are temporarily structured by oscillations. In this study, we aimed to reveal the
      mechanisms underlying the cannabinoid-induced decrease in gamma oscillations. We
      first verified that cannabinoids (CP55,940 and WIN55,212-2) readily suppressed
      carbachol-induced gamma oscillations in the CA3 region of hippocampal slices via
      activation of CB(1)Rs. The cannabinoid-induced decrease in the peak power of
      oscillations was accompanied by reduced and less precise firing activity in CA3
      pyramidal cells and fast spiking basket cells. By examining the cannabinoid
      sensitivity of synaptic inputs we found that the amplitude of evoked excitatory
      postsynaptic currents was significantly suppressed upon CB(1)R activation in both
      CA3 pyramidal cells and fast spiking basket cells. In contrast, evoked inhibitory
      postsynaptic currents in CA3 pyramidal cells were unaltered. Furthermore, we
      observed that a CB(1)R agonist-induced decrease in the oscillation power at the
      beginning of the drug application was accompanied primarily by the reduced
      discharge of fast spiking basket cells, while pyramidal cell firing was
      unaltered. This result implies that the dampening of cholinergically induced
      gamma oscillations in the hippocampus by cannabinoids can be explained by a
      reduced excitatory input predominantly onto fast spiking basket cells, which
      leads to a reduction in neuronal firing frequency and precision, and thus to
      smaller field potentials. In addition, we uncovered that the spontaneously
      occurring sharp wave-ripple activities in hippocampal slices could also be
      suppressed by CB(1)R activation suggesting that cannabinoids profoundly reduce
      the intrinsically generated oscillatory activities at distinct frequencies in CA3
      networks by reducing synaptic neurotransmission.

PMID- 21859824
TI  - Sex and ageing differences in resting arterial pressure regulation: the role of
      the beta-adrenergic receptors.
AB  - In men, muscle sympathetic nerve activity (MSNA) is positively related to total
      peripheral resistance (TPR) and inversely related to cardiac output (CO).
      However, this relationship was not observed in young women. We aimed to
      investigate whether simultaneous beta-adrenergic stimulation offsets this balance
      in young women. Furthermore, we aimed to examine whether the ability of the beta
      adrenergic receptors to offset the transduction of MSNA into vasoconstrictor tone
      was lost in postmenopausal women. We measured MSNA (peroneal microneurography),
      arterial pressure (brachial line), CO (Modelflow), TPR and changes in forearm
      vascular conductance (FVC) to increasing doses of noradrenaline (NA; 2, 4 and 8
      ng (100 ml)(-1) min(-1)) before and after systemic beta-blockade with propranolol
      in 17 young men, 17 young women and 15 postmenopausal (PM) women. The percentage
      and absolute change in FVC to the last two doses of NA were greater during beta
      blockade in young women (P < 0.05), whereas the change in FVC was similar before
      and during beta-blockade in young men and PM women (P > 0.05). Before beta
      blockade there was no relationship of MSNA to TPR or mean arterial pressure (MAP)
      in young women. Following beta-blockade, MSNA became positively related to TPR (r
      = 0.59, P < 0.05) and MAP (r = 0.58, P < 0.05). In the PM women and young men,
      MSNA was positively associated with TPR. beta-Blockade had no effect on this
      relationship. Our data suggest that the beta-adrenergic receptors offset alpha
      adrenergic vasoconstriction in young women but not young men or PM women. These
      findings may explain in part the tendency for blood pressure to rise after
      menopause in women.

PMID- 21859825
TI  - Purinergic signalling mobilizes mitochondrial Ca2+ in mouse Sertoli cells.
AB  - Intimate bidirectional communication between Sertoli cells and developing germ
      cells ensures the integrity and efficiency of spermatogenesis. Yet, a conceptual
      mechanistic understanding of the physiological principles that underlie Sertoli
      cell autocrine and paracrine signalling is lacking. Here, we characterize a
      purinergic Ca(2+) signalling network in immature mouse Sertoli cells that
      consists of both P2X2 and P2Y2 purinoceptor subtypes, the endoplasmic reticulum
      and, notably, mitochondria. By combining a transgenic mouse model with a
      dedicated bioluminescence imaging device, we describe a novel method to monitor
      mitochondrial Ca(2+) mobilization in Sertoli cells at subcellular spatial and
      millisecond temporal resolution. Our data identify mitochondria as essential
      components of the Sertoli cell signalling 'toolkit' that control the shape of
      purinergic Ca(2+) responses, and probably several other paracrine Ca(2+)
      dependent signals.

PMID- 21859826
TI  - Excessive erythrocytosis compromises the blood-endothelium interface in
      erythropoietin-overexpressing mice.
AB  - Elevated systemic haematocrit (Hct) increases risk of cardiovascular disorders,
      such as stroke and myocardial infarction. One possible pathophysiological
      mechanism could be a disturbance of the blood-endothelium interface. It has been
      shown that blood interacts with the endothelial surface via a thick hydrated
      macromolecular layer (the 'glycocalyx', or 'endothelial surface layer'--ESL),
      modulating various biological processes, including inflammation, permeability and
      atherosclerosis. However, the consequences of elevated Hct on the functional
      properties of this interface are incompletely understood. Thus, we combined
      intravital microscopy of an erythropoietin overexpressing transgenic mouse line
      (tg6) with excessive erythrocytosis (Hct 0.85), microviscometric analysis of
      haemodynamics, and a flow simulation model to assess the effects of elevated Hct
      on glycocalyx/ESL thickness and flow resistance. We show that the glycocalyx/ESL
      is nearly abolished in tg6 mice (thickness: wild-type control: 0.52 MUm; tg6:
      0.13 MUm; P < 0.001). However, the corresponding reduction in network flow
      resistance contributes <20% to the maintenance of total peripheral resistance
      observed in tg6 mice. This suggests that the pathological effects of elevated Hct
      in these mice, and possibly also in polycythaemic humans, may relate to
      biological corollaries of a reduced ESL thickness and the consequent alteration
      in the blood-endothelium interface, rather than to an increase of flow
      resistance.

PMID- 21859827
TI  - Regulator of G protein signaling 6 mediates doxorubicin-induced ATM and p53
      activation by a reactive oxygen species-dependent mechanism.
AB  - Doxorubicin (DXR), among the most widely used cancer chemotherapy agents,
      promotes cancer cell death via activation of ataxia telangiectasia mutated (ATM)
      and the resultant upregulation of tumor suppressor p53. The exact mechanism by
      which DXR activates ATM is not fully understood. Here, we discovered a novel role
      for regulator of G protein signaling 6 (RGS6) in mediating activation of ATM and
      p53 by DXR. RGS6 was robustly induced by DXR, and genetic loss of RGS6
      dramatically impaired DXR-induced activation of ATM and p53, as well as its in
      vivo apoptotic actions in heart. The ability of RGS6 to promote p53 activation in
      response to DXR was independent of RGS6 interaction with G proteins but required
      ATM. RGS6 mediated activation of ATM and p53 by DXR via a reactive oxygen species
      (ROS)-dependent and DNA damage-independent mechanism. This mechanism represents
      the primary means by which DXR promotes activation of the ATM-p53 apoptosis
      pathway that underlies its cytotoxic activity. Our findings contradict the
      canonical theories that DXR activates ATM primarily by promoting DNA damage
      either directly or indirectly (via ROS) and that RGS6 function is mediated by its
      interactions with G proteins. These findings reveal a new mechanism for the
      chemotherapeutic actions of DXR and identify RGS6 as a novel target for cancer
      chemotherapy.

PMID- 21859828
TI  - Evolution of tumor invasiveness: the adaptive tumor microenvironment landscape
      model.
AB  - Interactions between cancer cells and their microenvironment are crucial for
      promoting tumor growth and invasiveness. In the tumor adaptive landscape model,
      hypoxic and acidic microenvironmental conditions reduce the fitness of cancer
      cells and significantly restrict their proliferation. This selects for enhanced
      motility as cancer cells may evolve an invasive phenotype if the consequent cell
      movement is rewarded by proliferation. Here, we used an integrative approach
      combining a mathematical tumor adaptive landscape model with experimental studies
      to examine the evolutionary dynamics that promote an invasive cancer phenotype.
      Computer simulation results hypothesized an explicit coupling of motility and
      proliferation in cancer cells. The mathematical modeling results were also
      experimentally examined by selecting Panc-1 cells with enhanced motility on a
      fibroblast-derived 3-dimensional matrix for cells that move away from the
      unfavorable metabolic constraints. After multiple rounds of selection, the cells
      that adapted through increased motility were characterized for their phenotypic
      properties compared with stationary cells. Microarray and gene depletion studies
      showed the role of Rho-GDI2 in regulating both cell movement and proliferation.
      Together, this work illustrates the partnership between evolutionary mathematical
      modeling and experimental validation as a potentially useful approach to study
      the complex dynamics of the tumor microenvironment.

PMID- 21859830
TI  - Eribulin mesylate.
AB  - Eribulin mesylate, a nontaxane, completely synthetic microtubule inhibitor, has
      recently been approved by the U.S. Food and Drug Administration as third-line
      treatment of metastatic breast cancer refractory to anthracyclines and taxanes.
      Eribulin is a synthetic analogue of halichondrin B, which inhibits microtubule
      polymerization by a mechanism distinct from other available antitubulin agents.
      Eribulin significantly increased overall survival (OS; median OS for the eribulin
      treated group was 13.1 months versus 10.6 months for the group treated by
      investigator's choice) in a heavily pretreated metastatic breast cancer
      population. Eribulin has a manageable side-effect profile, notably neutropenia
      and fatigue, and a relatively low incidence of peripheral neuropathy. The
      mechanism of action, pharmacokinetics, preclinical antitumor activity, and
      clinical trials of eribulin in the metastatic breast cancer setting are reviewed
      here.

PMID- 21859829
TI  - Glioblastoma angiogenesis and tumor cell invasiveness are differentially
      regulated by beta8 integrin.
AB  - Glioblastoma multiforme (GBM) is a highly invasive brain tumor that develops
      florid microvascular proliferation and hemorrhage. However, mechanisms that favor
      invasion versus angiogenesis in this setting remain largely uncharacterized.
      Here, we show that integrin beta8 is an essential regulator of both GBM-induced
      angiogenesis and tumor cell invasiveness. Highly angiogenic and poorly invasive
      tumors expressed low levels of beta8 integrin, whereas highly invasive tumors
      with limited neovascularization expressed high levels of beta8 integrin.
      Manipulating beta8 integrin protein levels altered the angiogenic and invasive
      growth properties of GBMs, in part, reflected by a diminished activation of
      latent TGFbetas, which are extracellular matrix protein ligands for beta8
      integrin. Taken together, these results establish a role for beta8 integrin in
      differential control of angiogenesis versus tumor cell invasion in GBM. Our
      findings suggest that inhibiting beta8 integrin or TGFbeta signaling may diminish
      tumor cell invasiveness during malignant progression and following antivascular
      therapies.

PMID- 21859831
TI  - Protein kinase C zeta is a positive modulator of canonical Wnt signaling pathway
      in tumoral colon cell lines.
AB  - The colonic epithelium is a continuously renewing tissue with a dynamic turnover
      of cells. Wnt pathway is a key regulator of its homeostasis and is altered in a
      large proportion of colon cancers. Protein kinase C (PKC) family of
      serine/threonine kinases are also involved in colon tumor formation and
      progression; however, the molecular role played by them in the Wnt pathway, is
      poorly understood. Reciprocal coimmunoprecipitation and immunofluorescence
      studies revealed that PKCzeta interacts with beta-catenin mainly in tumoral colon
      cells, which overexpressed this PKC isoform. The pharmacological inhibition, the
      small interference RNA-mediated knockdown of PKCzeta or the expression of a
      dominant-negative form of it in tumoral SW480 cells, blocked in a dose-dependent
      manner the constitutive transcriptional activity mediated by beta-catenin, the
      cell proliferation and the expression of the Wnt target gene c-myc. Remarkably,
      the PKCzeta stably depleted cells exhibited diminished tumorigenic activity in
      grafted mice. We show that PKCzeta functions in a mechanism that does not involve
      beta-catenin degradation since the effects produced by PKCzeta inhibition were
      also obtained in the presence of proteosome inhibitor and in cells expressing a
      beta-catenin degradation-resistant mutant. It was found that PKCzeta activity
      regulates the nuclear localization of beta-catenin since PKCzeta inhibition
      induces a rapid export of beta-catenin from the nucleus to the cytoplasm in a
      Leptomycin B sensitive manner. Taken together, our results indicate that the
      atypical PKCzeta plays an important role in the positive regulation of canonical
      Wnt pathway.

PMID- 21859832
TI  - Interferon-signaling pathway: associations with colon and rectal cancer risk and
      subsequent survival.
AB  - Interferons (IFNs) are proteins involved in many functions including antiviral
      and antimicrobial response, apoptosis, cell cycle control and mediating other
      cytokines. IFN gamma (IFNG) is a proinflammatory cytokine that modulates many
      immune-related genes. In this study we examine genetic variation in IFNG, IFNGR1,
      IFNGR2 and interferon regulatory factors (IRFs) to determine associations with
      colon and rectal cancer and survival after diagnosis. We include data from two
      population-based incident studies of colon cancer (1555 cases and 1956 controls)
      and rectal cancer (754 cases and 959 controls). Five tagSNPs in IFNG, IRF2 and
      IRF3 were associated with colon cancer and eight tagSNPs in IFNGR1, IFNGR2, IRF2,
      IRF4, IRF6 and IRF8 were associated with rectal cancer. IRF3 rs2304204 was
      associated with the strongest direct association and IRF2 3775554 with the
      strongest inverse association for colon cancer [odds ratios (ORs) 1.43, 95%
      confidence interval (CI) 1.12-1.82 for recessive model and 0.52, 95% CI 0.28-0.97
      for unrestricted model]. For rectal cancer, IFNGR1 rs3799488 was directly
      associated with risk (OR 2.30, 95% CI 1.04-5.09 for recessive model), whereas
      IRF6 rs861020 was inversely associated with risk (OR 0.57, 95% CI 0.34-0.95).
      Several single-nucleotide polymorphisms interacted significant with both NF
      kappaB1 and IL6 and with aspirin/non-steroidal anti-inflammatory drugs and
      cigarette smoking. Using a summary score to estimate mutational load, we observed
      a hazard rate ratio (HRR) close to 5.00 (95% CI 2.73-8.99) for both colon and
      rectal (HRR 4.83, 95% CI 2.34-10.05) cancer for those in the category having the
      most at-risk genotypes. These data suggest the importance of IFN-signaling
      pathway on colon and rectal cancer risk and survival after diagnosis.

PMID- 21859834
TI  - Modelling genetic and clinical heterogeneity in epithelial ovarian cancers.
AB  - The biology underlying early-stage epithelial ovarian cancer (EOC) development is
      poorly understood. Identifying biomarkers associated with early-stage disease
      could have a significant impact on reducing mortality. Here, we describe
      establishment of a three-dimensional (3D) in vitro genetic model of EOC
      initiation and early-stage neoplastic progression. Normal primary ovarian
      epithelial (POE) cells, immortalized using hTERT (immortalised ovarian epithelial
      [IOE] cells), were partially transformed by overexpressing the CMYC oncogene
      (IOE(CMYC) cells). Subsequent expression of mutant alleles of KRAS (KRAS(G12V))
      or BRAF (BRAF(V600E)) created double-mutant lines (IOE(CMYC.KRAS) and
      IOE(CMYC.BRAF)). The transformed phenotype of IOE(CMYC) cells was further
      enhanced in concert with KRAS(G12V)/BRAF(V600E) expression, as in vitro analyses
      indicated that IOE(CMYC) cells had undergone morphological and phenotypic changes
      characteristic of neoplastic progression. When cultured as 3D spheroids, IOE
      cells underwent growth arrest, reminiscent of nonproliferative, unstimulated POE
      in vivo. In contrast, IOSE(CMYC+BRAF/KRAS) cells formed highly proliferative,
      poly-aggregate spheroid structures, showing increased expression of the Wilms
      tumour 1 tumourigenic marker and MIB1 proliferation marker. Transcriptomic
      analyses identified different gene expression profiles between the different cell
      lines and novel candidate genes (e.g. RGS4, CTGF and THBS1) that are somatically
      altered in EOCs. Gene expression signatures were compared with signatures from
      primary EOCs; tumours with IOE(CMYC) 'like' signatures were more likely to be
      high grade (P = 0.018); tumours with BRAF signatures were associated with
      improved relapse-free survival (P = 0.003). In conclusion, we have established in
      vitro 3D models of early-stage EOCs, which reflect genetic and phenotypic
      heterogeneity of the disease. Molecular genetic characteristics of these models
      correlated with molecular and clinical features of primary EOCs.

PMID- 21859833
TI  - Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia
      (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice.
AB  - Capsaicin is a major biologically active ingredient of chili peppers. Extensive
      studies indicate that capsaicin is a cancer-suppressing agent via blocking the
      activities of several signal transduction pathways including nuclear factor
      kappaB, activator protein-1 and signal transducer and activator of transcription
      3. However, there is little study on the effect of capsaicin on pancreatic
      carcinogenesis. In the present study, the effect of capsaicin on pancreatitis and
      pancreatic intraepithelial neoplasia (PanIN) was determined in a mutant Kras
      driven and caerulein-induced pancreatitis-associated carcinogenesis in LSL
      Kras(G12D)/Pdx1-Cre mice. Forty-five LSL-Kras(G12D)/Pdx1-Cre mice and 10 wild
      type mice were subjected to one dose of caerulein (250 MUg/kg body wt,
      intraperitoneally) at age 4 weeks to induce and synchronize the development of
      chronic pancreatitis and PanIN lesions. One week after caerulein induction,
      animals were randomly distributed into three groups and fed with either AIN-76A
      diet, AIN-76A diet containing 10 p.p.m. capsaicin or 20 p.p.m. capsaicin for a
      total of 8 weeks. The results showed that capsaicin significantly reduced the
      severity of chronic pancreatitis, as determined by evaluating the loss of acini,
      inflammatory cell infiltration and stromal fibrosis. PanIN formation was
      frequently observed in the LSL-Kras(G12D)/Pdx1-Cre mice. The progression of PanIN
      1 to high-grade PanIN-2 and -3 were significantly inhibited by capsaicin. Further
      immunochemical studies revealed that treatment with 10 and 20 p.p.m. capsaicin
      significantly reduced proliferating cell nuclear antigen-labeled cell
      proliferation and suppressed phosphorylation of extracellular signal-regulated
      kinase (ERK) and c-Jun as well blocked Hedgehog/GLI pathway activation. These
      results indicate that capsaicin could be a promising agent for the
      chemoprevention of pancreatic carcinogenesis, possibly via inhibiting
      pancreatitis and mutant Kras-led ERK activation.

PMID- 21859835
TI  - Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and
      upregulation of tumor suppressor proteins in human cervical cancer cells.
AB  - Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7
      oncoproteins, which are known to inactivate tumor suppressor proteins p53 and
      pRb, respectively. Repression of HPV oncoproteins would therefore result in
      reactivation of tumor suppressor pathways and cause apoptosis in cancer cells.
      Withaferin A (WA), the active component of the medicinal plant Withania
      Somnifera, has exhibited inhibitory effects against several different cancers. We
      examined the activity of WA on human cervical cancer cells in vitro and in vivo.
      WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50)
      0.45 +/- 0.05 MUM). Mechanistically, WA was found to (i) downregulate expression
      of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase
      levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear
      antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation
      of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its
      phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53
      mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA
      resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with
      essentially similar trend in the modulation of molecular markers as in vitro.
      This is the first demonstration indicating that WA significantly downregulates
      expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in
      apoptosis of cervical cancer cells. Together, our data suggest that WA can be
      exploited as a potent therapeutic agent for the treatment and prevention of
      cervical cancer without deleterious effects.

PMID- 21859836
TI  - Blood pressure in different gestational trimesters, fetal growth, and the risk of
      adverse birth outcomes: the generation R study.
AB  - Researchers have suggested that maternal hypertensive disorders during pregnancy
      affect fetal growth. The authors examined the associations between systolic and
      diastolic blood pressures in different trimesters of pregnancy and both
      repeatedly measured fetal growth characteristics and the risks of adverse birth
      outcomes. The present study (2001-2005) was performed in 8,623 women who were
      participating in a population-based prospective cohort study from fetal life
      onwards. Blood pressure and fetal growth characteristics were assessed in each
      trimester of pregnancy. Information on hypertensive complications and adverse
      birth outcomes was obtained from medical records. The results suggested that
      higher blood pressure was associated with smaller fetal head circumference and
      femur length, as well as lower fetal weight from the third trimester onward. An
      increase in blood pressure from the second trimester to the third trimester was
      associated with an increased risk of adverse birth outcomes. Compared with women
      who did not experience hypertension during pregnancy, women with preeclampsia had
      increased risks of having children who were preterm (odds ratio = 5.89, 95%
      confidence interval: 2.63, 13.14), had a low birth weight (odds ratio = 8.94, 95%
      confidence interval: 6.19, 12.90), or were small for their gestational age (odds
      ratio = 5.03, 95% confidence interval: 3.31, 7.62). The present results suggest
      that higher maternal blood pressure is associated with impaired fetal growth
      during the third trimester of pregnancy and increased risks of adverse birth
      outcomes.

PMID- 21859837
TI  - Does recognition of depression in primary care affect outcome? The PREDICT-NL
      study.
AB  - BACKGROUND: Detection rates of depression in primary care are <50%. Studies
      showed similar outcome after 12 months for recognized and unrecognized
      depression. Outcome beyond 12 months is less well studied. OBJECTIVE: We
      investigated recognition of depression in primary care and its relation to
      outcome after 6, 12 and 39 months. METHODS: Data were used from a prospective
      cohort study of 1293 consecutive general practice attendees (PREDICT-NL), who
      were followed up after 6 (n = 1236), 12 (n = 1179) and 39 (n = 752) months. We
      measured the presence and severity of major depressive disorder (MDD) according
      to DSM-IV criteria and Patient Health Questionnaire 9 (PHQ-9) and mental function
      with Short Form 12 (SF-12). Recognition of depression was assessed using
      international classification of primary care codes (P03 and P76) and Anatomical
      Therapeutic Chemical (N06A) codes from the GP records (6 months before/after
      baseline). RESULTS: At baseline, 170 (13%) of the participants had MDD, of whom
      36% were recognized by their GP. The relative risk of being depressed after 39
      months was 1.35 [95% confidence interval (CI) 0.7-2.7] for participants with
      recognized depression compared to unrecognized depression. At baseline,
      participants with recognized depression had more depressive symptoms (mean
      difference PHQ-9 2.7, 95% CI 1.6-3.9) and worse mental function (mean difference
      mental component summary -3.8, 95% CI -7.8 to 0.2) than unrecognized depressed
      participants. After 12 and 39 months, mean scores for both groups did not differ
      but were worse than those without depression. CONCLUSIONS: A minority of patients
      with MDD is recognized in primary care. Those who were unrecognized had
      comparable outcome after 12 and 39 months as participants with recognized
      depression.

PMID- 21859838
TI  - Digitoxin-induced cytotoxicity in cancer cells is mediated through distinct
      kinase and interferon signaling networks.
AB  - Cardiac glycosides (e.g., digoxin, digitoxin) constitute a diverse family of
      plant-derived sodium pump inhibitors that have been in clinical use for the
      treatment of heart-related diseases (congestive heart failure, atrial arrhythmia)
      for many years. Recently though, accumulating in vitro and in vivo evidence
      highlight potential anticancer properties of these compounds. Despite the fact
      that members of this family have advanced to clinical trial testing in cancer
      therapeutics, their cytotoxic mechanism is not yet elucidated. In this study, we
      investigated the cytotoxic properties of cardiac glycosides against a panel of
      pancreatic cancer cell lines, explored their apoptotic mechanism, and
      characterized the kinetics of cell death induced by these drugs. Furthermore, we
      deployed a high-throughput kinome screening approach and identified several
      kinases of the Na-K-ATPase-mediated signal transduction circuitry (epidermal
      growth factor receptor, Src, pkC, and mitogen-activated protein kinases) as
      important mediators downstream of cardiac glycoside cytotoxic action. To further
      extend our knowledge on their mode of action, we used mass-spectrometry-based
      quantitative proteomics (stable isotope labeling of amino acids in cell culture)
      coupled with bioinformatics to capture large-scale protein perturbations induced
      by a physiological dose of digitoxin in BxPC-3 pancreatic cancer cells and
      identified members of the interferon family as key regulators of the main
      protein/protein interactions downstream of digitoxin action. Hence, our findings
      provide more in-depth information regarding the molecular mechanisms underlying
      cardiac glycoside-induced cytotoxicity.

PMID- 21859841
TI  - NF-kappaB is required for Smac mimetic-mediated sensitization of glioblastoma
      cells for gamma-irradiation-induced apoptosis.
AB  - Evasion of apoptosis contributes to radioresistance of glioblastoma, calling for
      novel strategies to overcome apoptosis resistance. In this study, we investigated
      the potential of the small molecule Smac mimetic BV6 to modulate radiosensitivity
      of glioblastoma cells. Here, we identify a novel proapoptotic function of NF
      kappaB in gamma-irradiation-induced apoptosis of glioblastoma cells by showing,
      for the first time, that NF-kappaB is critically required for Smac mimetic
      mediated radiosensitization. BV6 significantly increases gamma-irradiation
      triggered apoptosis in several glioblastoma cell lines in a dose- and time
      dependent manner. Calculation of combination index (CI) reveals that the
      interaction of BV6 and gamma-irradiation is highly synergistic (CI < 0.3).
      Molecular studies show that BV6 stimulates NF-kappaB activation, which is
      critical for radiosensitization, because genetic inhibition of NF-kappaB by
      overexpression of the dominant-negative superrepressor IkappaBalpha-SR
      significantly decreases BV6- and gamma-irradiation-induced apoptosis. Also, the
      BV6-mediated enhancement of gamma-irradiation-triggered caspase activation, drop
      of mitochondrial membrane potential, and cytochrome c release is abolished in
      cells overexpressing IkappaBalpha-SR. Similarly, NF-kappaB inhibition by ectopic
      expression of a kinase dead mutant of IKKbeta prevents the BV6-mediated
      sensitization for gamma-irradiation. The clinical relevance is underscored by
      experiments with primary tumor samples showing that BV6 sensitizes primary
      cultured glioma cells as well as glioblastoma-initiating cancer stem cells
      derived from surgical specimens for gamma-irradiation. In conclusion, we identify
      NF-kappaB as a critical mediator of Smac mimetic-conferred radiosensitization of
      glioblastoma cells. These results have important implications for the development
      of Smac mimetic-based combination protocols for radiosensitization of
      glioblastoma.

PMID- 21859839
TI  - A molecular screening approach to identify and characterize inhibitors of
      glioblastoma stem cells.
AB  - Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a
      heterogeneous population of tumor cells among which a tumor-initiating and
      treatment-resistant subpopulation, here termed GBM stem cells, have been
      identified as primary therapeutic targets. Here, we describe a high-throughput
      small molecule screening approach that enables the identification and
      characterization of chemical compounds that are effective against GBM stem cells.
      The paradigm uses a tissue culture model to enrich for GBM stem cells derived
      from human GBM resections and combines a phenotype-based screen with gene target
      specific screens for compound identification. We used 31,624 small molecules from
      7 chemical libraries that we characterized and ranked based on their effect on a
      panel of GBM stem cell-enriched cultures and their effect on the expression of a
      module of genes whose expression negatively correlates with clinical outcome:
      MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting
      differential effects across cell types used, 4 compounds showed selectivity by
      inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched
      cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n
      palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the
      expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509
      and #5256360 were chosen for more detailed study and inhibited GBM stem cells in
      self-renewal assays in vitro and in a xenograft model in vivo. These studies show
      that our screening strategy provides potential candidates and a blueprint for
      lead compound identification in larger scale screens or screens involving other
      cancer types.

PMID- 21859840
TI  - A novel kinase inhibitor of FADD phosphorylation chemosensitizes through the
      inhibition of NF-kappaB.
AB  - Fas-associated protein with death domain (FADD) is a cytosolic adapter protein
      essential for mediating death receptor-induced apoptosis. It has also been
      implicated in a number of nonapoptotic activities including embryogenesis, cell
      cycle progression, cell proliferation, and tumorigenesis. Our recent studies have
      shown that high levels of phosphorylated FADD (p-FADD) in tumor cells correlate
      with increased activation of the antiapoptotic transcription factor NF-kappaB and
      is a biomarker for aggressive disease and poor clinical outcome. These findings
      suggest that inhibition of FADD phosphorylation is a viable target for cancer
      therapy. A high-throughput screen using a cell-based assay for monitoring FADD
      kinase activity identified NSC 47147 as a small molecule inhibitor of FADD
      phosphorylation. The compound was evaluated in live cells and mouse tumors for
      its efficacy as an inhibitor of FADD-kinase activity through the inhibition of
      casein kinase 1alpha. NSC 47147 was shown to decrease levels of p-FADD and NF
      kappaB activity such that combination therapy leads to greater induction of
      apoptosis and enhanced tumor control than either agent alone. The studies
      described here show the utility of bioluminescent cell-based assays for the
      identification of active compounds and the validation of drug-target interaction
      in a living subject. In addition, the presented results provide proof-of
      principle studies as to the validity of targeting FADD-kinase activity as a novel
      cancer therapy strategy.

PMID- 21859842
TI  - Targeting HSP 90 induces apoptosis and inhibits critical survival and
      proliferation pathways in multiple myeloma.
AB  - The second most commonly diagnosed hematologic malignancy, multiple myeloma,
      affects predominantly older patients (>60s) and is characterized by paraprotein
      in the serum or urine. Clinical manifestations include anemia, hypercalcaemia,
      progressive renal impairment, and osteolytic bone destruction. Despite promising
      new therapies, multiple myeloma eventually relapses in almost all patients. HSP
      are ubiquitous and highly conserved in prokaryotes and eukaryote organisms.
      Exposure to a broad range of stimuli results in increased HSP protein expression.
      These chaperone proteins are involved in protein transportation, prevent protein
      aggregation, and ensure correct folding of nascent and stress-accumulated
      misfolded proteins. In cancer, HSP expression is dysregulated, resulting in
      elevated expression, which promotes cancer by preventing programmed cell death
      and supporting autonomous cells growth, ultimately leading to resistance to heat,
      chemotherapy, and other stresses. Client proteins of HSP90 such as AKT, p53, MEK,
      STAT3, and Bcr-Abl are vital in tumor progression, including multiple myeloma,
      and their maturation and stability is dependent on HSP90. Therefore, inhibition
      of HSP90 via a HSP90 inhibitor (such as NVP-HSP990) should interrupt multiple
      signaling pathways essential for oncogenesis and growth in multiple myeloma. Our
      study showed that NVP-HSP990 triggered apoptosis in a panel of human multiple
      myeloma cells, induced cell-cycle arrest, PARP cleavage, downregulation of client
      proteins, the inability to reactivate phospho-STAT3 following exogenous IL-6
      stimulation, and it synergized with azacytidine and bortezomib in cell lines and
      primary multiple myeloma samples. The mechanism of HSP90 inhibition in multiple
      myeloma warrants further evaluation.

PMID- 21859843
TI  - Developmental timing of CCM2 loss influences cerebral cavernous malformations in
      mice.
AB  - Cerebral cavernous malformations (CCM) are vascular malformations of the central
      nervous system (CNS) that lead to cerebral hemorrhages. Familial CCM occurs as an
      autosomal dominant condition caused by loss-of-function mutations in one of the
      three CCM genes. Constitutive or tissue-specific ablation of any of the Ccm genes
      in mice previously established the crucial role of Ccm gene expression in
      endothelial cells for proper angiogenesis. However, embryonic lethality precluded
      the development of relevant CCM mouse models. Here, we show that endothelial
      specific Ccm2 deletion at postnatal day 1 (P1) in mice results in vascular
      lesions mimicking human CCM lesions. Consistent with CCM1/3 involvement in the
      same human disease, deletion of Ccm1/3 at P1 in mice results in similar CCM
      lesions. The lesions are located in the cerebellum and the retina, two organs
      undergoing intense postnatal angiogenesis. Despite a pan-endothelial Ccm2
      deletion, CCM lesions are restricted to the venous bed. Notably, the consequences
      of Ccm2 loss depend on the developmental timing of Ccm2 ablation. This work
      provides a highly penetrant and relevant CCM mouse model.

PMID- 21859844
TI  - Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1
      infection.
AB  - Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of
      the plasma membrane and modulate multiple cellular functions. We report that ATP
      is released from HIV-1 target cells through pannexin-1 channels upon interaction
      between the HIV-1 envelope protein and specific target cell receptors.
      Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate
      proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane
      depolarization, which in turn stimulate fusion between Env-expressing membranes
      and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition
      of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2)
      impairs the replication of HIV-1 mutant viruses that are resistant to
      conventional antiretroviral agents. Altogether, our results reveal a novel
      signaling pathway involved in the early steps of HIV-1 infection that may be
      targeted with new therapeutic approaches.

PMID- 21859845
TI  - CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic
      cell-associated antigen.
AB  - Cells undergoing programmed cell death (apoptosis) are removed in situ by
      macrophages and dendritic cells (DCs) through a specialized form of phagocytosis
      (efferocytosis). In the lung, there are two primary DC subsets with the potential
      to migrate to the local lymph nodes (LNs) and initiate adaptive immune responses.
      In this study, we show that only CD103(+) DCs were able to acquire and transport
      apoptotic cells to the draining LNs and cross present apoptotic cell-associated
      antigen to CD8 T cells. In contrast, both the CD11b(hi) and the CD103(+) DCs were
      able to ingest and traffic latex beads or soluble antigen. CD103(+) DCs
      selectively exhibited high expression of TLR3, and ligation of this receptor led
      to enhanced in vivo cytotoxic T cell responses to apoptotic cell-associated
      antigen. The selective role for CD103(+) DCs was confirmed in Batf3(-/-) mice,
      which lack this DC subtype. Our findings suggest that CD103(+) DCs are the DC
      subset in the lung that captures and presents apoptotic cell-associated antigen
      under homeostatic and inflammatory conditions and raise the possibility for more
      focused immunological targeting to CD8 T cell responses.

PMID- 21859846
TI  - Targeting cap-dependent translation blocks converging survival signals by AKT and
      PIM kinases in lymphoma.
AB  - New anticancer drugs that target oncogenic signaling molecules have greatly
      improved the treatment of certain cancers. However, resistance to targeted
      therapeutics is a major clinical problem and the redundancy of oncogenic
      signaling pathways provides back-up mechanisms that allow cancer cells to escape.
      For example, the AKT and PIM kinases produce parallel oncogenic signals and share
      many molecular targets, including activators of cap-dependent translation. Here,
      we show that PIM kinase expression can affect the clinical outcome of lymphoma
      chemotherapy. We observe the same in animal lymphoma models. Whereas
      chemoresistance caused by AKT is readily reversed with rapamycin, PIM-mediated
      resistance is refractory to mTORC1 inhibition. However, both PIM- and AKT
      expressing lymphomas depend on cap-dependent translation, and genetic or
      pharmacological blockade of the translation initiation complex is highly
      effective against these tumors. The therapeutic effect of blocking cap-dependent
      translation is mediated, at least in part, by decreased production of short-lived
      oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves.
      Hence, targeting the convergence of oncogenic survival signals on translation
      initiation is an effective alternative to combinations of kinase inhibitors.

PMID- 21859847
TI  - A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated
      immunity.
AB  - It is known that vitamin A and its metabolite, retinoic acid (RA), are essential
      for host defense. However, the mechanisms for how RA controls inflammation are
      incompletely understood. The findings presented in this study show that RA
      signaling occurs concurrent with the development of inflammation. In models of
      vaccination and allogeneic graft rejection, whole body imaging reveals that RA
      signaling is temporally and spatially restricted to the site of inflammation.
      Conditional ablation of RA signaling in T cells significantly interferes with
      CD4(+) T cell effector function, migration, and polarity. These findings provide
      a new perspective of the role of RA as a mediator directly controlling CD4(+) T
      cell differentiation and immunity.

PMID- 21859848
TI  - Design and application of group-specific oligonucleotide probes for detecting and
      monitoring mouse clostridia.
AB  - Clostridia dominate the rodent intestinal bacterial community and play an
      important role in physiological functions of the host. However, their ecology and
      diversity are still unclear. In our previous report, we showed that
      phylogenetically novel groups of clostridia inhabit the mouse intestine and
      contribute to the normalization of germfree mice. In this study, five new
      oligonucleotide probes were designed and applied to detect these clostridial
      groups that are essential for the normalization of germfree mice. Faecal
      microbiota of conventional mouse strains and specific pathogen-free mice from
      different breeding colonies were analysed by fluorescence in situ hybridization
      using these five probes. Our results showed that the composition of clostridia
      differed among mouse strains and also among mouse groups of the same inbred
      strain from different breeding colonies. These five new probes for mouse
      clostridia were able to detect the difference in clostridial diversity in each
      mouse group. In addition to Clostridium, we also analysed Bacteroides and
      Lactobacillus using previously described probes and the number or the frequency
      of occurrence of Bacteroides was shown to be different among mouse groups
      analysed. The oligonucleotide probe set including our newly developed and
      previously described probes used in this study can be applied to monitoring of
      significant groups of mouse intestinal microbiota.

PMID- 21859849
TI  - Identification of inflammatory biomarkers for pediatric malarial anemia severity
      using novel statistical methods.
AB  - Areas where Plasmodium falciparum transmission is holoendemic are characterized
      by high rates of pediatric severe malarial anemia (SMA) and associated mortality.
      Although the etiology of SMA is complex and multifactorial, perturbations in
      inflammatory mediator production play an important role in the pathogenic
      process. As such, the current study focused on identification of inflammatory
      biomarkers in children with malarial anemia. Febrile children (3 to 30 months of
      age) presenting at Siaya District Hospital in western Kenya underwent a complete
      clinical and hematological evaluation. Children with falciparum malaria and no
      additional identifiable anemia-promoting coinfections were stratified into three
      groups: uncomplicated malaria (hemoglobin [Hb] levels of >=11.0 g/dl; n = 31),
      non-SMA (Hb levels of 6.0 to 10.9 g/dl; n = 37), and SMA (Hb levels of <6.0 g/dl;
      n = 80). A Luminex hu25-plex array was used to determine potential biomarkers
      (i.e., interleukin 1beta [IL-1beta], IL-1 receptor antagonist [IL-1Ra], IL-2, IL
      2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, tumor
      necrosis factor alpha [TNF-alpha], alpha interferon [IFN-alpha], IFN-gamma,
      granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage
      inflammatory protein 1 alpha [MIP-1alpha], MIP-1beta, IFN-inducible protein of 10
      kDa [IP-10], monokine induced by IFN-gamma [MIG], eotaxin, RANTES, and monocyte
      chemoattractant protein 1 [MCP-1]) in samples obtained prior to any treatment
      interventions. To determine the strongest biomarkers of anemia, a parsimonious
      set of predictor variables for Hb was generated by least-angle regression (LAR)
      analysis, controlling for the confounding effects of age, gender, glucose-6
      phosphate dehydrogenase (G6PD) deficiency, and sickle cell trait, followed by
      multiple linear regression analyses. IL-12p70 and IFN-gamma emerged as positive
      predictors of Hb, while IL-2R, IL-13, and eotaxin were negatively associated with
      Hb. The results presented here demonstrate that the IL-12p70/IFN-gamma pathway
      represents a set of biomarkers that predicts elevated Hb levels in children with
      falciparum malaria, while activation of the IL-13/eotaxin pathway favors more
      profound anemia.

PMID- 21859850
TI  - Resistance to Yersinia pestis infection decreases with age in B10.T(6R) mice.
AB  - We demonstrate that 2-month-old female B10.T(6R) mice are highly resistant to
      systemic infection with the KIM5 strain of Yersinia pestis and that B10.T(6R)
      mice become susceptible to Y. pestis infection by the age of 5 months. In this
      study, young (2-month-old) and middle-aged (5- to 12-month-old) B10.T(6R) mice
      were infected with equal CFU counts of Y. pestis. The 50% lethal dose (LD(50))
      for young B10.T(6R) mice was ~1.4 * 10(4) CFU, while middle-aged B10.T(6R) mice
      exhibited an LD(50) of ~60 CFU. Elevated bacterial burdens were found in the
      spleens of middle-aged mice at 24 and 60 h and in the livers at 60 h
      postinfection. Immune cell infiltration was greater in the livers of resistant
      young mice than in those of middle-aged mice and mice of the susceptible C57BL/6N
      strain. Unlike susceptible mice, young B10.T(6R) mice did not develop necrotic
      lesions throughout the liver. Instead, livers from young B10.T(6R) mice contained
      granuloma-like structures. Immunohistochemical staining of liver sections from
      these mice at 60 h postinfection revealed that the majority of immune cells
      present in these structures were neutrophils. These findings suggest that
      resistance to plague in B10.T(6R) mice correlates with early formation of
      neutrophilic lesions in the liver.

PMID- 21859851
TI  - Vaccine immunity to coccidioidomycosis occurs by early activation of three signal
      pathways of T helper cell response (Th1, Th2, and Th17).
AB  - We have previously reported that C57BL/6 mice vaccinated with a live, attenuated
      mutant of Coccidioides posadasii, referred to as the DeltaT vaccine, are fully
      protected against pulmonary coccidioidomycosis. This model was used here to
      explore the nature of vaccine immunity during the initial 2-week period after
      intranasal challenge. Elevated neutrophil and eosinophil infiltration into the
      lungs of nonvaccinated mice contrasted with markedly reduced recruitment of these
      cells in vaccinated animals. The numbers of lung-infiltrated macrophages and
      dendritic cells showed a progressive increase in vaccinated mice and corresponded
      with reduction of the lung infection. Concentrations of selected inflammatory
      cytokines and chemokines were initially higher in lung homogenates of vaccinated
      mice but then generally decreased at 14 days postchallenge in correlation with
      containment of the organism and apparent dampening of the inflammation of host
      tissue. Profiles of cytokines detected in lung homogenates of DeltaT-vaccinated
      mice were indicative of a mixed T helper 1 (Th1)-, Th2-, and Th17-type immune
      response, a conclusion which was supported by detection of lung infiltration of
      activated T cells with the respective CD4(+) gamma interferon (IFN-gamma)(+),
      CD4(+) interleukin-5 (IL-5)(+), and CD4(+) IL-17A(+) phenotypes. While Th1 and
      Th2 immunity was separately dispensed of by genetic manipulation without loss of
      DeltaT vaccine-mediated protection, loss of functional Th17 cells resulted in
      increased susceptibility to infection in immunized mice. Characterization of the
      early events of protective immunity to Coccidioides infection in vaccinated mice
      contributes to the identification of surrogates of immune defense and provides
      potential insights into the design of immunotherapeutic protocols for treatment
      of coccidioidomycosis.

PMID- 21859852
TI  - The iron-responsive Fur/RyhB regulatory cascade modulates the Shigella outer
      membrane protease IcsP.
AB  - Actin-based motility is central to the pathogenicity of the intracellular
      bacterial pathogen Shigella. Two Shigella outer membrane proteins, IcsA and IcsP,
      are required for efficient actin-based motility in the host cell cytoplasm, and
      the genes encoding both proteins are carried on the large virulence plasmid. IcsA
      triggers actin polymerization on the surface of the bacterium, leading to the
      formation of an actin tail that allows both intra- and intercellular spread.
      IcsP, an outer membrane protease, modulates the amount and distribution of the
      IcsA protein on the bacterial surface through proteolytic cleavage of IcsA.
      Transcription of icsP is increased in the presence of VirB, a DNA-binding protein
      that positively regulates many genes carried on the large virulence plasmid. In
      Shigella dysenteriae, the small regulatory RNA RyhB, which is a member of the
      iron-responsive Fur regulon, suppresses several virulence-associated phenotypes
      by downregulating levels of virB in response to iron limitation. Here we show
      that the Fur/RyhB regulatory pathway downregulates IcsP levels in response to low
      iron concentrations in Shigella flexneri and that this occurs at the level of
      transcription through the RyhB-dependent regulation of VirB. These observations
      demonstrate that in Shigella species the Fur/RyhB regulatory pathway provides a
      mechanism to finely tune the expression of icsP in response to the low
      concentrations of free iron predicted to be encountered within colonic epithelial
      cells.

PMID- 21859853
TI  - A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has
      rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects
      on virulence.
AB  - Macrophage infectivity potentiators (Mips) are a group of virulence factors
      encoded by pathogenic bacteria such as Legionella, Chlamydia, and Neisseria
      species. Mips are part of the FK506-binding protein (FKBP) family, whose members
      typically exhibit peptidylprolyl cis-trans isomerase (PPIase) activity which is
      inhibitable by the immunosuppressants FK506 and rapamycin. Here we describe the
      identification and characterization of BPSS1823, a Mip-like protein in the
      intracellular pathogen Burkholderia pseudomallei. Recombinant BPSS1823 protein
      has rapamycin-inhibitable PPIase activity, indicating that it is a functional
      FKBP. A mutant strain generated by deletion of BPSS1823 in B. pseudomallei
      exhibited a reduced ability to survive within cells and significant attenuation
      in vivo, suggesting that BPSS1823 is important for B. pseudomallei virulence. In
      addition, pleiotropic effects were observed with a reduction in virulence
      mechanisms, including resistance to host killing mechanisms, swarming motility,
      and protease production.

PMID- 21859855
TI  - Tobacco smoking affects bacterial acquisition and colonization in oral biofilms.
AB  - Recent evidence suggests that smoking affects the composition of the disease
      associated subgingival biofilm, yet little is known about its effects during the
      formation of this biofilm. The present investigation was undertaken to examine
      the contributions of smoking to the composition and proinflammatory
      characteristics of the biofilm during de novo plaque formation. Marginal and
      subgingival plaque and gingival crevicular fluid samples were collected from 15
      current smokers and from 15 individuals who had never smoked (nonsmokers)
      following 1, 2, 4, and 7 days of undisturbed plaque formation. 16S rRNA gene
      cloning and sequencing were used for bacterial identification, and multiplex bead
      based flow cytometry was used to quantify the levels of 27 immune mediators.
      Smokers demonstrated a highly diverse, relatively unstable initial colonization
      of both marginal and subgingival biofilms, with lower niche saturation than that
      seen in nonsmokers. Periodontal pathogens belonging to the genera Fusobacterium,
      Cardiobacterium, Synergistes, and Selenomonas, as well as respiratory pathogens
      belonging to the genera Haemophilus and Pseudomonas, colonized the early biofilms
      of smokers and continued to persist over the observation period, suggesting that
      smoking favors early acquisition and colonization of pathogens in oral biofilms.
      Smokers also demonstrated an early proinflammatory response to this colonization,
      which persisted over 7 days. Further, a positive correlation between
      proinflammatory cytokine levels and commensal bacteria was observed in smokers
      but not in nonsmokers. Taken together, the data suggest that smoking influences
      both the composition of the nascent biofilm and the host response to this
      colonization.

PMID- 21859854
TI  - Ehrlichia chaffeensis TRP120 binds a G+C-rich motif in host cell DNA and exhibits
      eukaryotic transcriptional activator function.
AB  - Ehrlichia chaffeensis is an obligately intracellular bacterium that modulates
      host cell gene transcription in the mononuclear phagocyte, but the host gene
      targets and mechanisms involved in transcriptional modulation are not well
      defined. In this study, we identified a novel tandem repeat DNA-binding domain in
      the E. chaffeensis 120-kDa tandem repeat protein (TRP120) that directly binds
      host cell DNA. TRP120 was observed by immunofluorescent microscopy in the nucleus
      of E. chaffeensis-infected host cells and was detected in nuclear extracts by
      Western immunoblotting with TRP120-specific antibody. The TRP120 binding sites
      and associated host cell target genes were identified using high-throughput deep
      sequencing (Illumina) of immunoprecipitated DNA (chromatin immunoprecipitation
      and high-throughput DNA sequencing). Multiple em motif elicitation (MEME)
      analysis of the most highly enriched TRP120-bound sequences revealed a G+C-rich
      DNA motif, and recombinant TRP120 specifically bound synthetic oligonucleotides
      containing the motif. TRP120 target gene binding sites were mapped most
      frequently to intersecting regions (intron/exon; 49%) but were also identified in
      upstream regulatory regions (25%) and downstream locations (26%). Genes targeted
      by TRP120 were most frequently associated with transcriptional regulation, signal
      transduction, and apoptosis. TRP120 targeted inflammatory chemokine genes, CCL2,
      CCL20, and CXCL11, which were strongly upregulated during E. chaffeensis
      infection and were also upregulated by direct transfection with recombinant
      TRP120. This study reveals that TRP120 is a novel DNA-binding protein that is
      involved in a host gene transcriptional regulation strategy.

PMID- 21859856
TI  - SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium,
      can promote biofilm formation and provides limited protection against infection.
AB  - Salmonella enterica is a major cause of morbidity worldwide and mortality in
      children and immunocompromised individuals in sub-Saharan Africa. Outer membrane
      proteins of Salmonella are of significance because they are at the interface
      between the pathogen and the host, they can contribute to adherence,
      colonization, and virulence, and they are frequently targets of antibody-mediated
      immunity. In this study, the properties of SadA, a purported trimeric
      autotransporter adhesin of Salmonella enterica serovar Typhimurium, were
      examined. We demonstrated that SadA is exposed on the Salmonella cell surface in
      vitro and in vivo during infection of mice. Expression of SadA resulted in cell
      aggregation, biofilm formation, and increased adhesion to human intestinal Caco-2
      epithelial cells. Immunization of mice with folded, full-length, purified SadA
      elicited an IgG response which provided limited protection against bacterial
      challenge. When anti-SadA IgG titers were enhanced by administering alum
      precipitated protein, a modest additional protection was afforded. Therefore,
      despite SadA having pleiotropic functions, it is not a dominant, protective
      antigen for antibody-mediated protection against Salmonella.

PMID- 21859857
TI  - Ehrlichia chaffeensis TRP120 interacts with a diverse array of eukaryotic
      proteins involved in transcription, signaling, and cytoskeleton organization.
AB  - Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits
      tropism for mononuclear phagocytes and survives by evading host cell defense
      mechanisms. Recently, molecular interactions between E. chaffeensis 47-kDa tandem
      repeat (TR) protein (TRP47) and the eukaryotic host cell have been described. In
      this investigation, yeast (Saccharomyces cerevisiae) two-hybrid analysis
      demonstrated that E. chaffeensis-secreted tandem repeat protein 120 (TRP120)
      interacts with a diverse group of host cell proteins associated with major
      biological processes, including transcription and regulation, cell signaling,
      protein trafficking, and actin cytoskeleton organization. Twelve target proteins
      with the highest frequency of interaction with TRP120 were confirmed by
      cotransformation in yeast. Host targets, including human immunoglobulin lambda
      locus (IGL), cytochrome c oxidase subunit II (COX2), Golgi-associated gamma
      adaptin ear-containing ARF binding protein 1 (GGA1), polycomb group ring finger 5
      (PCGF5), actin gamma 1 (ACTG1), and unc-13 homolog D (UNC13D; Caenorhabditis
      elegans), colocalized strongly with TRP120 in HeLa cells and with E. chaffeensis
      dense-cored morulae and areas adjacent to morulae in the host cytoplasm. The TR
      domain of TRP120 interacted only with PCGF5, indicating that distinct TRP120
      domains contribute to specific host target interactions and that multiple domains
      are required to reconstitute TRP120 interactions with other host targets. Three
      previously defined molecular interactions between TRP47 and host proteins, PCGF5,
      IGLL1, and CAP1, were also associated with TRP120, demonstrating that molecular
      cross talk occurs between Ehrlichia TRPs and host targets. These findings further
      support the role of TRPs as effectors that reprogram the host cell.

PMID- 21859858
TI  - Alejandro Sanchez Alvarado: bootstrapping flatworms into the molecular age.

PMID- 21859860
TI  - The histone methyltransferase Set7/9 promotes myoblast differentiation and
      myofibril assembly.
AB  - The molecular events that modulate chromatin structure during skeletal muscle
      differentiation are still poorly understood. We report in this paper that
      expression of the H3-K4 histone methyltransferase Set7 is increased when
      myoblasts differentiate into myotubes and is required for skeletal muscle
      development, expression of muscle contractile proteins, and myofibril assembly.
      Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs
      skeletal muscle differentiation, accompanied by a decrease in levels of histone
      monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance
      expression of muscle differentiation genes. Expression of myocyte enhancer factor
      2 and genes encoding contractile proteins is decreased in Set7 knockdown
      myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene
      expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of
      myogenic differentiation genes. Together, our experiments define a biological
      function for Set7 in muscle differentiation and provide a molecular mechanism by
      which Set7 modulates myogenic transcription factors during muscle
      differentiation.

PMID- 21859861
TI  - Wee1 controls genomic stability during replication by regulating the Mus81-Eme1
      endonuclease.
AB  - Correct replication of the genome and protection of its integrity are essential
      for cell survival. In a high-throughput screen studying H2AX phosphorylation, we
      identified Wee1 as a regulator of genomic stability. Wee1 down-regulation not
      only induced H2AX phosphorylation but also triggered a general deoxyribonucleic
      acid (DNA) damage response (DDR) and caused a block in DNA replication, resulting
      in accumulation of cells in S phase. Wee1-deficient cells showed a decrease in
      replication fork speed, demonstrating the involvement of Wee1 in DNA replication.
      Inhibiting Wee1 in cells treated with short treatment of hydroxyurea enhanced the
      DDR, which suggests that Wee1 specifically protects the stability of stalled
      replication forks. Notably, the DDR induced by depletion of Wee1 critically
      depends on the Mus81-Eme1 endonuclease, and we found that codepletion of Mus81
      and Wee1 abrogated the S phase delay. Importantly, Wee1 and Mus81 interact in
      vivo, suggesting direct regulation. Altogether, these results demonstrate a novel
      role of Wee1 in controlling Mus81 and DNA replication in human cells.

PMID- 21859859
TI  - The evolution of the cytoskeleton.
AB  - The cytoskeleton is a system of intracellular filaments crucial for cell shape,
      division, and function in all three domains of life. The simple cytoskeletons of
      prokaryotes show surprising plasticity in composition, with none of the core
      filament-forming proteins conserved in all lineages. In contrast, eukaryotic
      cytoskeletal function has been hugely elaborated by the addition of accessory
      proteins and extensive gene duplication and specialization. Much of this
      complexity evolved before the last common ancestor of eukaryotes. The
      distribution of cytoskeletal filaments puts constraints on the likely prokaryotic
      line that made this leap of eukaryogenesis.

PMID- 21859862
TI  - c-Jun N-terminal kinase phosphorylates DCP1a to control formation of P bodies.
AB  - Cytokines and stress-inducing stimuli signal through c-Jun N-terminal kinase
      (JNK) using a diverse and only partially defined set of downstream effectors. In
      this paper, the decapping complex subunit DCP1a was identified as a novel JNK
      target. JNK phosphorylated DCP1a at residue S315 in vivo and in vitro and
      coimmunoprecipitated and colocalized with DCP1a in processing bodies (P bodies).
      Sustained JNK activation by several different inducers led to DCP1a dispersion
      from P bodies, whereas IL-1 treatment transiently increased P body number.
      Inhibition of TAK1-JNK signaling also affected the number and size of P bodies
      and the localization of DCP1a, Xrn1, and Edc4. Transcriptome analysis further
      identified a central role for DCP1a in IL-1-induced messenger ribonucleic acid
      (mRNA) expression. Phosphomimetic mutation of S315 stabilized IL-8 but not
      IkappaBalpha mRNA, whereas overexpressed DCP1a blocked IL-8 transcription and
      suppressed p65 NF-kappaB nuclear activity. Collectively, these data reveal DCP1a
      as a multifunctional regulator of mRNA expression and suggest a novel mechanism
      controlling the subcellular localization of DCP1a in response to stress or
      inflammatory stimuli.

PMID- 21859864
TI  - Health care funding model flawed, blue-ribbon CMA panel argues.

PMID- 21859865
TI  - Health care system needs new revenue streams, expert argues.

PMID- 21859867
TI  - Middle-of-the-night medicine is rarely patient-centred.

PMID- 21859863
TI  - Ran-dependent docking of importin-beta to RanBP2/Nup358 filaments is essential
      for protein import and cell viability.
AB  - RanBP2/Nup358, the major component of the cytoplasmic filaments of the nuclear
      pore complex (NPC), is essential for mouse embryogenesis and is implicated in
      both macromolecular transport and mitosis, but its specific molecular functions
      are unknown. Using RanBP2 conditional knockout mouse embryonic fibroblasts and a
      series of mutant constructs, we show that transport, rather than mitotic,
      functions of RanBP2 are required for cell viability. Cre-mediated RanBP2
      inactivation caused cell death with defects in M9- and classical nuclear
      localization signal (cNLS)-mediated protein import, nuclear export signal
      mediated protein export, and messenger ribonucleic acid export but no apparent
      mitotic failure. A short N-terminal RanBP2 fragment harboring the NPC-binding
      domain, three phenylalanine-glycine motifs, and one Ran-binding domain (RBD)
      corrected all transport defects and restored viability. Mutation of the RBD
      within this fragment caused lethality and perturbed binding to Ran guanosine
      triphosphate (GTP)-importin-beta, accumulation of importin-beta at nuclear pores,
      and cNLS-mediated protein import. These data suggest that a critical function of
      RanBP2 is to capture recycling RanGTP-importin-beta complexes at cytoplasmic
      fibrils to allow for adequate cNLS-mediated cargo import.

PMID- 21859868
TI  - Pyoderma gangrenosum associated with chronic polyarthritis.

PMID- 21859869
TI  - Alternative financing for health care: a path to sustainability?

PMID- 21859870
TI  - Incidence of potentially avoidable urgent readmissions and their relation to all
      cause urgent readmissions.
AB  - BACKGROUND: Urgent, unplanned hospital readmissions are increasingly being used
      to gauge the quality of care. We reviewed urgent readmissions to determine which
      were potentially avoidable and compared rates of all-cause and avoidable
      readmissions. METHODS: In a multicentre, prospective cohort study, we reviewed
      all urgent readmissions that occurred within six months among patients discharged
      to the community from 11 teaching and community hospitals between October 2002
      and July 2006. Summaries of the readmissions were reviewed by at least four
      practising physicians using standardized methods to judge whether the readmission
      was an adverse event (poor clinical outcome due to medical care) and whether the
      adverse event could have been avoided. We used a latent class model to determine
      whether the probability that each readmission was truly avoidable exceeded 50%.
      RESULTS: Of the 4812 patients included in the study, 649 (13.5%, 95% confidence
      interval [CI] 12.5%-14.5%) had an urgent readmission within six months after
      discharge. We considered 104 of them (16.0% of those readmitted, 95% CI 13.3%
      19.1%; 2.2% of those discharged, 95% CI 1.8%-2.6%) to have had a potentially
      avoidable readmission. The proportion of patients who had an urgent readmission
      varied significantly by hospital (range 7.5%-22.5%; chi(2) = 92.9, p < 0.001);
      the proportion of readmissions deemed avoidable did not show significant
      variation by hospital (range 1.2%-3.7%; chi(2) = 12.5, p < 0.25). We found no
      association between the proportion of patients who had an urgent readmission and
      the proportion of patients who had an avoidable readmission (Pearson correlation
      0.294; p = 0.38). In addition, we found no association between hospital rankings
      by proportion of patients readmitted and rankings by proportion of patients with
      an avoidable readmission (Spearman correlation coefficient 0.28, p = 0.41).
      INTERPRETATION: Urgent readmissions deemed potentially avoidable were relatively
      uncommon, comprising less than 20% of all urgent readmissions following hospital
      discharge. Hospital-specific proportions of patients who were readmitted were not
      related to proportions with a potentially avoidable readmission.

PMID- 21859872
TI  - National assessment of cancer drugs commences.

PMID- 21859873
TI  - Five things to know about...Imaging in urolithiasis.

PMID- 21859874
TI  - The deadly effects of violence against medical workers in war zones.

PMID- 21859875
TI  - The doctor is in--your workplace.

PMID- 21859876
TI  - 'Modern life is rubbish'.

PMID- 21859877
TI  - Learning our way into the future public health: a proposition.
AB  - This article attempts to bridge the gap between the values and skills that
      currently inform public health and those that we need to confront the future. We
      draw on a set of radical arguments. Firstly, the ability of modern people to
      understand, predict and control the natural world has brought many benefits but
      evidence is accumulating that the methods and mindsets of modernity are subject
      to diminishing returns and adverse effects. This is manifest in the rise of new
      epidemics: obesity, addiction-related harm, loss of well-being, rising rates of
      depression and anxiety and widening inequalities. Secondly, there is little
      evidence that people are embracing new forms of thinking or practice, despite
      other threats which have the potential for massive effects on many lives, such as
      climate change and peak oil. Thirdly, if the problems we face may indicate that
      'modernity' is in decline because unsustainable, then profound change is
      necessary if we are to avoid collapse. This analysis suggests that public health
      needs a new approach. We set out propositions and models that could help us learn
      our way into the future.

PMID- 21859878
TI  - Learning our way in the future public health: extending the proposition.

PMID- 21859879
TI  - The future of public health: the lessons of modernism.

PMID- 21859880
TI  - Essential components of public health evidence reviews: capturing intervention
      complexity, implementation, economics and equity.

PMID- 21859881
TI  - NICE public health guidance update.

PMID- 21859882
TI  - Toxicologic pathology in a multicultural world--India.
AB  - The global practice of drug development is expanding into many different
      continents and countries. India, in particular, is rapidly emerging as an
      economic force in this arena by offering ever-expanding opportunities for
      pharmaceutical market expansion as well as productive drug development
      partnerships. The key to the country's current socioeconomic success appears to
      be education, particularly the development of higher and professional education.
      Also, recent modifications to India's patent laws offer greater protections and
      incentives for international investment. Increasing numbers of competent contract
      research organizations create attractive opportunities for large Western
      pharmaceutical companies with a desire to gain access to burgeoning markets as
      well as mitigate the rising cost of drug development with less costly services.
      Well-trained veterinary pathologists are available, appropriate facilities are
      being constructed, and laboratory capabilities are expanding. Developing a
      productive partnership with a credible laboratory service in India, as with any
      new provider, requires due diligence and knowledgeable scrutiny of key elements
      of the work stream, such as facilities, education and training of laboratory
      personnel, Good Laboratory Practices, animal care, timelines, and data
      management. Ultimately and with appropriate management, mutually beneficial drug
      development partnerships are available in India.

PMID- 21859883
TI  - Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in
      rats and mice.
AB  - Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the
      potential for widespread exposure, the lack of chronic toxicity and
      carcinogenicity data, and the known carcinogenicity of structurally related
      compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by
      inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6
      hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP
      resulted in significantly increased incidences of adenomas of the large intestine
      and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the
      epididymis was statistically significantly increased at 500 ppm, but the
      biological significance of this common lesion is unclear. Incidences of
      pancreatic islet adenoma in male rats were significantly increased at all
      concentrations relative to concurrent controls but were within the historical
      control range for inhalation studies. There was no evidence of carcinogenic
      activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences
      of alveolar/bronchiolar neoplasms of the lung were present in female mice.
      Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions
      in the nose of rats and mice, the larynx of rats and male mice, the trachea of
      female rats and male and female mice, and the lungs of mice. Inflammatory lesions
      with Splendore Hoeppli (S-H) material were present primarily in the nose and skin
      of exposed male and female rats, indicating that 1-BP caused immunosuppression.

PMID- 21859884
TI  - Induction of heart valve lesions by small-molecule ALK5 inhibitors.
AB  - Aberrant signaling by transforming growth factor-beta (TGF-beta) and its type I
      (ALK5) receptor has been implicated in a number of human diseases and this
      pathway is considered a potential target for therapeutic intervention.
      Transforming growth factor-beta signaling via ALK5 plays a critical role during
      heart development, but the role of ALK5 in the adult heart is poorly understood.
      In the current study, the preclinical toxicology of ALK5 inhibitors from two
      different chemistry scaffolds was explored. Ten-week-old female Han Wistar rats
      received test compounds by the oral route for three to seven days. Both compounds
      induced histopathologic heart valve lesions characterized by hemorrhage,
      inflammation, degeneration, and proliferation of valvular interstitial cells. The
      pathology was observed in all animals, at all doses tested, and occurred in all
      four heart valves. Immunohistochemical analysis of ALK5 in rat hearts revealed
      expression in the valves, but not in the myocardium. Compared to control animals,
      protein levels of ALK5 were unchanged in the heart valves of treated animals. We
      also observed a physeal dysplasia in the femoro-tibial joint of rats treated with
      ALK5 inhibitors, a finding consistent with a pharmacological effect described
      previously with ALK5 inhibitors. Overall, these findings suggest that TGF-beta
      signaling via ALK5 plays a critical role in maintaining heart valve integrity.

PMID- 21859885
TI  - Neuropathology standards: what constitutes an optimal histomorphologic evaluation
      of the nervous system in general toxicity studies.
AB  - The identification of neurotoxicity is a critical issue in drug development, and
      toxicologic pathologists play an important role in this effort. Neuropathology is
      a specialized area of toxicologic pathology in which a substantial number of
      nonroutine techniques and methods have been developed, and there are undoubtedly
      many instances in which these specialized procedures have helped characterize a
      neuropathologic lesion. Routine histopathologic methods employed in general
      toxicologic pathology studies are needed to identify the complete range of
      possible neuropathologic changes; once identified, many of these changes can be
      better defined by specialized techniques, such as immunohistochemistry, to
      confirm cell types involved. Sometimes, when neurotoxicity is expected, dedicated
      studies can be designed a priori and optimized for detection of the anticipated
      effects. However, when neurotoxicity arises unexpectedly or there is uncertainty
      around the potential for neurotoxicity, the decision of what to do can become
      more difficult. Recommendations to go ahead and perform the "optimal" study
      design that would accommodate all the potentially useful specialized techniques
      for characterizing a neuropathologic change are sometimes not practical and can
      be unnecessary and potentially detrimental to other end points in the study. In
      addition, there is not always agreement on when specialized techniques would be
      required and which ones should be used when necessary. Two techniques in
      particular that are commonly recommended to help facilitate the detection of
      neuropathologic lesions are perfusion fixation and the Fluoro-Jade stain.

PMID- 21859886
TI  - Asymptomatic macrothrombocytopenia in a young pure-bred beagle dog: a case
      report.
AB  - During baseline evaluation prior to a preclinical safety study, a 10-month-old
      male pure-bred Beagle dog was found to have marked thrombocytopenia (6 * 10(3)
      platelets [PLT]/uL) associated with a mean platelet volume (MPV) of 17.9 fL.
      Tests for Rickettsia rickettsii, Ehrlichia canis, and Borrelia burgdorferi were
      negative. Buccal bleeding time was normal. Over 3 months, PLT were 4 to 141 *
      10(3) PLT/uL, and MPV was 11.4 to 25.1 fL; however, PLT were <50 * 10(3) PLT/uL
      and MPV was >16 fL during most of this period. Antinuclear antibody (ANA) and
      anti-PLT antibody tests were negative. Genotyping for the presence of a beta 1
      tubulin mutation demonstrated the normal wild-type gene. Treatment with
      prednisone resulted in normal values after only 3 days. Ultrastructure of
      enlarged PLT was consistent with that of immature PLT, characterized by reduced
      numbers of peripheral microtubules and the presence of rough endoplasmic
      reticulum, free ribosomes, Golgi apparatus, and a prominent canalicular system.
      PLT ultrastructure and glucocorticoid responsiveness supported a diagnosis of
      immune-mediated thrombocytopenia that was masked by the cyclic nature of PLT
      decreases and lack of clinical signs. Inclusion of such a dog in a preclinical
      safety study could result in misinterpretation of clinical pathology findings.

PMID- 21859887
TI  - ICH S9: Developing anticancer drugs, one year later.
AB  - International Conference on Harmonisation of Technical Requirements for
      Registration of Pharmaceuticals for Human Use (ICH) S9 is the first international
      regulatory guidance document devoted to a specific therapeutic area, highlighting
      its importance in harmonizing regulatory expectations for the nonclinical
      development of therapeutics designed to treat advanced cancer. ICH S9
      successfully outlines the core requirements for the nonclinical development of
      novel oncology therapeutics, and the unique risk-benefit considerations for
      expediting drug development to treat these most grievous diseases. However,
      development companies and regulatory agencies have had limited opportunity to
      apply this guidance, so our collective experience in developing therapeutics
      under the guidance is limited. Discussed here are several key areas of ambiguity
      in the guidance, including identification of the patient population, selection of
      the initial safe dose for first-in-human trials, and requirements for nonclinical
      recovery data.

PMID- 21859888
TI  - Negative elongation factor accelerates the rate at which heat shock genes are
      shut off by facilitating dissociation of heat shock factor.
AB  - Promoter-proximal pausing of RNA polymerase II (Pol II) occurs on thousands of
      genes in animal cells. This pausing often correlates with the rapid induction of
      genes, but direct tests of the relationship between pausing and induction rates
      are lacking. hsp70 and hsp26 in Drosophila are rapidly induced by heat shock.
      Contrary to current expectations, depletion of negative elongation factor (NELF),
      a key factor in setting up paused Pol II, reduced pausing but did not interfere
      with rapid induction. Instead, depletion of NELF delayed the time taken for these
      genes to shut off during recovery from heat shock. NELF depletion also delayed
      the dissociation of HSF from hsp70 and hsp26, and a similar delay was observed
      when cells were depleted of the histone acetyltransferase CBP. CBP has been
      reported to associate with Pol II, and acetylation of HSF by CBP has been
      implicated in inhibiting the DNA-binding activity of HSF. We propose that NELF
      mediated pausing allows Pol II to direct CBP-mediated acetylation of HSF, thus
      causing HSF to dissociate from the gene. Activators are typically viewed as
      controlling Pol II. Our results reveal a possible reciprocal relationship in
      which paused Pol II influences the activator.

PMID- 21859889
TI  - SWI/SNF- and RSC-catalyzed nucleosome mobilization requires internal DNA loop
      translocation within nucleosomes.
AB  - The multisubunit SWI/SNF and RSC complexes utilize energy derived from ATP
      hydrolysis to mobilize nucleosomes and render the DNA accessible for various
      nuclear processes. Here we test the idea that remodeling involves intermediates
      with mobile DNA bulges or loops within the nucleosome by cross-linking the H2A N-
      or C-terminal tails together to generate protein "loops" that constrict
      separation of the DNA from the histone surface. Analyses indicate that this
      intranucleosomal cross-linking causes little or no change in remodeling-dependent
      exposure of DNA sequences within the nucleosome to restriction enzymes. However,
      cross-linking inhibits nucleosome mobilization and blocks complete movement of
      nucleosomes to extreme end positions on the DNA fragments. These results are
      consistent with evidence that nucleosome remodeling involves intermediates with
      DNA loops on the nucleosome surface but indicate that such loops do not freely
      diffuse about the surface of the histone octamer. We propose a threading model
      for movement of DNA loops around the perimeter of the nucleosome core.

PMID- 21859890
TI  - Competitive regulation of nucleolin expression by HuR and miR-494.
AB  - The RNA-binding protein (RBP) nucleolin promotes the expression of several
      proliferative proteins. Nucleolin levels are high in cancer cells, but the
      mechanisms that control nucleolin expression are unknown. Here, we show that
      nucleolin abundance is controlled posttranscriptionally via factors that
      associate with its 3' untranslated region (3'UTR). The RBP HuR was found to
      interact with the nucleolin (NCL) 3'UTR and specifically promoted nucleolin
      translation without affecting nucleolin mRNA levels. In human cervical carcinoma
      HeLa cells, analysis of a traceable NCL 3'UTR bearing MS2 RNA hairpins revealed
      that NCL RNA was mobilized to processing bodies (PBs) after silencing HuR,
      suggesting that the repression of nucleolin translation may occur in PBs.
      Immunoprecipitation of MS2-tagged NCL 3'UTR was used to screen for endogenous
      repressors of nucleolin synthesis. This search identified miR-494 as a microRNA
      that potently inhibited nucleolin expression, enhanced NCL mRNA association with
      argonaute-containing complexes, and induced NCL RNA transport to PBs.
      Importantly, miR-494 and HuR functionally competed for modulation of nucleolin
      expression. Moreover, the promotion of cell growth previously attributed to HuR
      was due in part to the HuR-elicited increase in nucleolin expression. Our
      collective findings indicate that nucleolin expression is positively regulated by
      HuR and negatively regulated via competition with miR-494.

PMID- 21859892
TI  - Combinatorial antibody library from multiple sclerosis patients reveals
      antibodies that cross-react with myelin basic protein and EBV antigen.
AB  - Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with
      unknown etiology. It is increasingly evident that, together with pathogenic T
      cells, autoreactive B cells are among the major players in MS development. The
      analysis of myelin neuroantigen-specific antibody repertoires and their possible
      cross-reactivity against environmental antigens, including viral proteins, could
      shed light on the mechanism of MS induction and progression. A phage display
      library of single-chain variable fragments (scFvs) was constructed from blood
      lymphocytes of patients with MS as a potential source of representative MS
      autoantibodies. Structural alignment of 13 clones selected toward myelin basic
      protein (MBP), one of the major myelin antigens, showed high homology within
      variable regions with cerebrospinal fluid MS-associated antibodies as well as
      with antibodies toward Epstein-Barr latent membrane protein 1 (LMP1). Three scFv
      clones showed pronounced specificity to MBP fragments 65-92 and 130-156, similar
      to the serum MS antibodies. One of these clones, designated E2, in both scFv and
      full-size human antibody constructs, was shown to react with both MBP and LMP1
      proteins in vitro, suggesting natural cross-reactivity. Thus, antibodies induced
      against LMP1 during Epstein-Barr virus infection might act as inflammatory
      trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS
      pathogenesis.

PMID- 21859891
TI  - BID binds to replication protein A and stimulates ATR function following
      replicative stress.
AB  - Proapoptotic BH3-interacting death domain agonist (BID) regulates apoptosis and
      the DNA damage response. Following replicative stress, BID associates with
      proteins of the DNA damage sensor complex, including replication protein A (RPA),
      ataxia telangiectasia and Rad3 related (ATR), and ATR-interacting protein
      (ATRIP), and facilitates an efficient DNA damage response. We have found that BID
      stimulates the association of RPA with components of the DNA damage sensor
      complex through interaction with the basic cleft of the N-terminal domain of the
      RPA70 subunit. Disruption of the BID-RPA interaction impairs the association of
      ATR-ATRIP with chromatin as well as ATR function, as measured by CHK1 activation
      and recovery of DNA replication following hydroxyurea (HU). We further
      demonstrate that the association of BID with RPA stimulates the association of
      ATR-ATRIP to the DNA damage sensor complex. We propose a model in which BID
      associates with RPA and stimulates the recruitment and/or stabilization of ATR
      ATRIP to the DNA damage sensor complex.

PMID- 21859893
TI  - An essential role for Stat3 in regulating IgG immune complex-induced pulmonary
      inflammation.
AB  - Growing evidence suggests that transcription factor signal transducer and
      activator of transcription (Stat) 3 may play an important regulatory role during
      inflammation. However, the function of Stat3 in acute lung injury (ALI) is
      largely unknown. In the current study, by using an adenoviral vector expressing a
      dominant-negative Stat3 isoform (Ad-Stat3-EVA), we determined the role of Stat3
      in IgG immune complex (IC)-induced inflammatory responses and injury in the lung
      from C57BL/6J mice. We show that IgG IC-induced DNA binding activity of Stat3 in
      the lung was significantly inhibited by Stat3-EVA. We demonstrate that both lung
      vascular permeability (albumin leak) and lung myeloperoxidase accumulation in the
      Ad-Stat-EVA treated mice were substantially reduced when compared with values in
      mice receiving control virus (Ad-GFP) during the injury. Furthermore,
      intratracheal administration of Ad-Stat3-EVA caused significant decreases in the
      contents of neutrophils, inflammatory cytokines (TNF-alpha and IL-6), chemokines
      [keratinocyte cell-derived chemokine, macrophage inflammatory protein (MIP)
      1alpha, and MIP-1beta], and complement component C5a in bronchoalveolar lavage
      fluids. Using Stat3-specific small interfering RNA, we show that knocking down
      Stat3 expression in alveolar macrophages (MH-S cells) significantly reduced the
      production of proinflammatory mediators on IgG IC stimulation. These data suggest
      that Stat3 plays an essential role in the pathogenesis of IgG IC-induced ALI by
      mediating the acute inflammatory responses in the lung and alveolar macrophages.

PMID- 21859894
TI  - KCNE2 forms potassium channels with KCNA3 and KCNQ1 in the choroid plexus
      epithelium.
AB  - Cerebrospinal fluid (CSF) is crucial for normal function and mechanical
      protection of the CNS. The choroid plexus epithelium (CPe) is primarily
      responsible for secreting CSF and regulating its composition by mechanisms
      currently not fully understood. Previously, the heteromeric KCNQ1-KCNE2 K(+)
      channel was functionally linked to epithelial processes including gastric acid
      secretion and thyroid hormone biosynthesis. Here, using Kcne2(-/-) tissue as a
      negative control, we found cerebral expression of KCNE2 to be markedly enriched
      in the CPe apical membrane, where we also discovered expression of KCNQ1.
      Targeted Kcne2 gene deletion in C57B6 mice increased CPe outward K(+) current 2
      fold. The Kcne2 deletion-enhanced portion of the current was inhibited by XE991
      (10 MUM) and margatoxin (10 MUM) but not by dendrotoxin (100 nM), indicating that
      it arose from augmentation of KCNQ subfamily and KCNA3 but not KCNA1 K(+) channel
      activity. Kcne2 deletion in C57B6 mice also altered the polarity of CPe KCNQ1 and
      KCNA3 trafficking, hyperpolarized the CPe membrane by 9 +/- 2 mV, and increased
      CSF [Cl(-)] by 14% compared with wild-type mice. These findings constitute the
      first report of CPe dysfunction caused by cation channel gene disruption and
      suggest that KCNE2 influences blood-CSF anion flux by regulating KCNQ1 and KCNA3
      in the CPe.

PMID- 21859895
TI  - Disc1 regulates both beta-catenin-mediated and noncanonical Wnt signaling during
      vertebrate embryogenesis.
AB  - Disc1 is a schizophrenia risk gene that engages multiple signaling pathways
      during neurogenesis and brain development. Using the zebrafish as a tool, we
      analyze the function of zebrafish Disc1 (zDisc1) at the earliest stages of brain
      and body development. We define a "tool" as a biological system that gives
      insight into mechanisms underlying a human disorder, although the system does not
      phenocopy the disorder. A zDisc1 peptide binds to GSK3beta, and zDisc1 directs
      early brain development and neurogenesis, by promoting beta-catenin-mediated Wnt
      signaling and inhibiting GSK3beta activity. zDisc1 loss-of-function embryos
      additionally display a convergence and extension phenotype, demonstrated by
      abnormal movement of dorsolateral cells during gastrulation, through changes in
      gene expression, and later through formation of abnormal, U-shaped muscle
      segments, and a truncated tail. These phenotypes are caused by alterations in the
      noncanonical Wnt pathway, via Daam and Rho signaling. The convergence and
      extension phenotype can be rescued by a dominant negative GSK3beta construct,
      suggesting that zDisc1 inhibits GSK3beta activity during noncanonical Wnt
      signaling. This is the first demonstration that Disc1 modulates the noncanonical
      Wnt pathway and suggests a previously unconsidered mechanism by which Disc1 may
      contribute to the etiology of neuropsychiatric disorders.

PMID- 21859896
TI  - MyD88-dependent production of IL-17F is modulated by the anaphylatoxin C5a via
      the Akt signaling pathway.
AB  - The interleukin-17 (IL-17) family of cytokines plays important roles in innate
      immune defenses against bacterial and fungal pathogens. While much is known about
      IL-17A, much less information is available about the IL-17F isoform. Here, we
      investigated gene expression and release of IL-17F and its regulation by the
      complement system. IL-17F was produced in mouse peritoneal elicited macrophages
      after TLR4 activation by LPS, peaking after 12 h. This effect was completely
      dependent on the presence of the adaptor protein MyD88. The copresence of the
      complement activation product, C5a (EC(50)=10 nM), amplified IL-17F production
      via the receptor C5aR. In vitro signaling studies indicated that LPS or C5a, or
      the combination, caused phosphorylation of Akt occurring at threonine 308 but not
      at serine 473. Treatment of macrophages with pharmacologic inhibitors of PI3K-Akt
      greatly reduced production of IL-17F as well as mRNA for IL-17F. In endotoxemia,
      C5a levels peaked at 6 h, while IL-17F levels peaked between 6-12 h. Full in vivo
      production of IL-17F during endotoxemia required C5a. A similar result was found
      in the cecal ligation and puncture sepsis model. These data suggest that maximal
      production of IL-17F requires complement activation and presence of C5a.

PMID- 21859897
TI  - Treatment of thyroid cancer with the new oral agents.

PMID- 21859898
TI  - A phase II study of YM155, a novel small-molecule suppressor of survivin, in
      castration-resistant taxane-pretreated prostate cancer.
AB  - BACKGROUND: YM155, a small-molecule survivin suppressor, showed modest single
      agent activity in a phase I study of heavily pretreated patients. This study was
      conducted to determine the activity of YM155 in patients with castration
      resistant prostate cancer (CRPC) who received prior taxane therapy. PATIENTS AND
      METHODS: Patients received 4.8 mg/m(2)/day of YM155 over 168-h continuous i.v.
      infusion every 3 weeks. Study end points included prostate-specific antigen (PSA)
      response, objective tumor response, safety, progression-free survival (PFS) and
      overall survival (OS). RESULTS: Thirty-five patients were enrolled. Two of 32
      (6.2%) assessable patients had a PSA response and 2 additional patients had PSA
      decrements >50% but not confirmed. One of 16 (6.2%) patients also had a partial
      response per RECIST V1. Median PFS and OS were 3.1 and 11.2 months, respectively.
      The most common adverse events were fatigue (63%), nausea (40%), anorexia (31%),
      constipation (31%), fever (26%) and vomiting (26%). CONCLUSIONS: YM155 has modest
      activity in taxane-pretreated CRPC with 25% of patients having prolonged stable
      disease (>=18 weeks). The regimen appears to be well tolerated. Based on the
      mechanism of action and preclinical evidence of synergy with docetaxel
      (Taxotere), YM155 combined with docetaxel is being evaluated in patients with
      CRPC.

PMID- 21859899
TI  - Update on desmoid tumors.
AB  - Desmoid tumors (DTs) are histologically benign proliferations of stromal cells
      but may grow locally aggressive. Overall, DTs are rare (0.03% of all neoplasms).
      A minority of DTs is associated with Gardner syndrome and mutations of the
      familial adenomatous polyposis (FAP) gene. Most spontaneous DTs are associated
      with mutations of the beta-catenin gene. This mutation results in the activation
      of Wnt/catenin signaling. Due to their variable clinical presentation and
      behavior, no standard approach for DTs can be recommended. In most cases of DTs
      of the extremities surgical extirpation is indicated, whereas in many other
      cases, a multimodal and multidisciplinary concept should be followed. In this
      review article, we discuss the diagnosis, pathogenesis, and treatment options for
      DTs, including targeted therapy with tyrosine kinase inhibitors.

PMID- 21859901
TI  - Developmental evaluation: building innovations in complex environments.
AB  - Developmental evaluation is an emerging approach to program evaluation that
      emphasizes innovation and learning. It is particularly well suited to evaluating
      innovative programs in their earliest stages of development and adapting existing
      programs to complex or changing environments. Key features of the developmental
      evaluation approach include a tight integration between evaluators and program
      staff and the use of data for continuous program improvement. This article
      presents developmental evaluation as a complementary approach to the traditional
      formative-summative evaluation cycle, especially when used for preformative
      evaluation. To illustrate this emerging approach, the article features a case
      example from the Illinois Caucus for Adolescent Health's evaluation of its school
      board sexuality education policy change project. The article concludes by
      suggesting ways that developmental evaluation can be useful in health promotion
      practice.

PMID- 21859902
TI  - The pull of the past: when do habits persist despite conflict with motives?
AB  - To identify the factors that disrupt and maintain habit performance, two field
      experiments tested the conditions under which people eat out of habit, leading
      them to resist motivational influences. Habitual popcorn eaters at a cinema were
      minimally influenced by their hunger or how much they liked the food, and they
      ate equal amounts of stale and fresh popcorn. Yet, mechanisms of automaticity
      influenced habit performance: Participants ate out of habit, regardless of
      freshness, only when currently in the context associated with past performance
      (i.e., a cinema; Study 1) and only when eating in a way that allowed them to
      automatically execute the response cued by that context (i.e., eating with their
      dominant hand; Study 2). Across all conditions, participants with weaker cinema
      popcorn-eating habits ate because of motivations such as liking for the popcorn.
      The findings reveal how habits resist conflicting motives and provide insight
      into promising mechanisms of habit change.

PMID- 21859900
TI  - Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at
      relapse in patients with muscle-invasive bladder cancer submitted to radical
      cystectomy: an Italian, multicenter, randomized phase III trial.
AB  - BACKGROUND: The purpose of the study was to evaluate the benefit of adjuvant
      chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder
      cancer (MIBC). PATIENTS AND METHODS: One hundred and ninety-four patients with
      pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to
      control (92 patients) or to four courses of AC (102 patients). These latter
      patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days
      1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin
      70 mg/m(2) day 15, every 28 days. RESULTS: At a median follow-up of 35 months,
      the 5-year overall survival (OS) was 48.5%, with no difference between the two
      arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99].
      Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage.
      The control and AC arms had comparable disease-free survival (42.3% and 37.2%,
      respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received
      the planned cycles. A significant higher incidence of thrombocytopenia was
      observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global
      quality of life was observed in the two arms. CONCLUSION: The study was
      underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS
      and disease-free survival in patients with MIBC.

PMID- 21859903
TI  - The measurement of platelet-poor plasma serotonin: a systematic review of prior
      reports and recommendations for improved analysis.
AB  - BACKGROUND: Recent reports of new and important roles for serotonin (5
      hydroxytryptamine, 5-HT) in the periphery have substantially increased interest
      in measuring peripheral serotonin. Nearly all circulating serotonin is found
      within platelets and this pool has been assessed by measuring serotonin in whole
      blood or in platelet-rich plasma. Measurement of the much smaller but potentially
      critically important pool of human free plasma serotonin in platelet-poor plasma
      (PPP) has proven much more difficult, with a wide range of reference values
      reported. CONTENT: To characterize the available data we carried out a systematic
      literature search of previous reports of PPP serotonin and attempted to determine
      the best estimate of true PPP serotonin concentration in humans. A total of 101
      published reports that included PPP serotonin values in healthy controls were
      found and included in the summary statistical analyses. The distribution of PPP
      serotonin values demonstrated high skewness (+1.98), and the reported values
      ranged from 0.6 to 179 nmol/L, with a mean of 31.6 nmol/L, an SD of 38.9 nmol/L,
      and a median of 14.8 nmol/L. SUMMARY: Reported concentrations for human PPP or
      free plasma serotonin were highly discrepant, with most reports giving
      erroneously high values that should be disregarded. Inherent difficulties in
      selectively measuring the extremely low concentrations of serotonin present in
      PPP and in preparing PPP without contamination from platelet-derived serotonin
      contributed to the problem, as did the failure of researchers to compare their
      results with those from prior studies. There is a clear and pressing need for
      reference materials for the measurement of plasma (PPP) serotonin.

PMID- 21859904
TI  - Digital microfluidic platform for multiplexing enzyme assays: implications for
      lysosomal storage disease screening in newborns.
AB  - BACKGROUND: Newborn screening for lysosomal storage diseases (LSDs) has been
      gaining considerable interest owing to the availability of enzyme replacement
      therapies. We present a digital microfluidic platform to perform rapid,
      multiplexed enzymatic analysis of acid alpha-glucosidase (GAA) and acid alpha
      galactosidase to screen for Pompe and Fabry disorders. The results were compared
      with those obtained using standard fluorometric methods. METHODS: We performed
      bench-based, fluorometric enzymatic analysis on 60 deidentified newborn dried
      blood spots (DBSs), plus 10 Pompe-affected and 11 Fabry-affected samples, at Duke
      Biochemical Genetics Laboratory using a 3-mm punch for each assay and an
      incubation time of 20 h. We used a digital microfluidic platform to automate
      fluorometric enzymatic assays at Advanced Liquid Logic Inc. using extract from a
      single punch for both assays, with an incubation time of 6 h. Assays were also
      performed with an incubation time of 1 h. RESULTS: Assay results were generally
      comparable, although mean enzymatic activity for GAA using microfluidics was
      approximately 3 times higher than that obtained using bench-based methods, which
      could be attributed to higher substrate concentration. Clear separation was
      observed between the normal and affected samples at both 6- and 1-h incubation
      times using digital microfluidics. CONCLUSIONS: A digital microfluidic platform
      compared favorably with a clinical reference laboratory to perform enzymatic
      analysis in DBSs for Pompe and Fabry disorders. This platform presents a new
      technology for a newborn screening laboratory to screen LSDs by fully automating
      all the liquid-handling operations in an inexpensive system, providing rapid
      results.

PMID- 21859907
TI  - A syndemic analysis of alcohol use and sexual risk behavior among tourism
      employees in Sosua, Dominican Republic.
AB  - The Dominican Republic has high rates of HIV infection and alcohol consumption.
      Unfortunately, little research has been focused on the broader sources of the
      synergy between these two health outcomes. We draw on syndemic theory to argue
      that alcohol consumption and sexual risk behavior are best analyzed within the
      context of culture and economy in Caribbean tourism spaces, which produce a
      synergy between apparently independent outcomes. We sampled 32 men and women
      working in the tourism industry at alcohol-serving establishments in Sosua,
      Dominican Republic. Interviewees described alcohol consumption as an implicit
      requirement of tourism work, tourism industry business practices that foster
      alcohol consumption, and an intertwining relationship between alcohol and sexual
      commerce. The need to establish relationships with tourists, combined with the
      overconsumption of alcohol, contributed to a perceived loss of sexual control,
      which participants felt could impede condom use. Interventions should incorporate
      knowledge of the social context of tourism areas to mitigate the contextual
      factors that contribute to HIV infection and alcohol consumption among locals.

PMID- 21859908
TI  - Assessing content validity of the patient generated index using cognitive
      interviews.
AB  - The effects of cancer and its treatment on quality of life contribute to patient
      and clinician decisions. Health-related quality of life (HRQL) is a subjective
      concept, leading to variation in its definition. This presents challenges when
      measuring HRQL and evaluating interventions. The designers of the Patient
      Generated Index (PGI) addressed these challenges by having individuals identify
      areas of their lives affected by illness and treatment, then report on these self
      defined areas. We used cognitive interviews to collect information about patient
      understanding of the PGI, the response processes used to complete the PGI, and
      how well the PGI reflected participant HRQL. Interview data support the content
      validity of the PGI in comprehensively defining and adequately sampling
      participant HRQL as an individualized construct. Findings also support our
      recommendation to revise PGI formatting to reduce response errors. We make
      recommendations to reduce the cognitive demands the PGI places on respondents.

PMID- 21859909
TI  - Pediatric injuries attributable to falls from windows in the United States in
      1990-2008.
AB  - OBJECTIVE: To examine the epidemiological features of pediatric injuries related
      to falls from windows. METHODS: By using the National Electronic Injury
      Surveillance System, emergency department (ED) data for pediatric injury cases
      associated with window falls in 1990-2008 were reviewed. RESULTS: An estimated 98
      415 children (95% confidence interval [CI]: 82 416-114 419) were treated in US
      hospital EDs for window fall-related injuries during the 19-year study period
      (average: 5180 patients per year [95% CI: 4828-5531]). The mean age of children
      was 5.1 years, and boys accounted for 58.1% of cases. One-fourth (25.4%) of the
      patients required admission to the hospital. The annual injury rate decreased
      significantly during the study period because of a decrease in the annual injury
      rate among 0- to 4-year-old children. Children 0 to 4 years of age were more
      likely to sustain head injuries (injury proportion ratio [IPR]: 3.22 [95% CI:
      2.65-3.91]) and to be hospitalized or to die (IPR: 1.65 [95% CI: 1.38-1.97])
      compared with children 5 to 17 years of age. Children who landed on hard surfaces
      were more likely to sustain head injuries (IPR: 2.05 [95% CI: 1.53-2.74]) and to
      be hospitalized or to die (IPR: 2.23 [95% CI: 1.57-3.17]) compared with children
      who landed on cushioning surfaces. CONCLUSIONS: To our knowledge, this is the
      first study to investigate window fall-related injuries treated in US hospital
      EDs by using a nationally representative sample. These injuries are an important
      pediatric public health problem, and increased prevention efforts are needed,
      including development and evaluation of innovative prevention programs.

PMID- 21859910
TI  - Parental sedentary restriction, maternal parenting style, and television viewing
      among 10- to 11-year-olds.
AB  - OBJECTIVE: To examine whether parenting styles or practices were associated with
      children's television (TV) viewing. METHODS: A total of 431 parent-child dyads
      (10- to 11-year-old children) from Bristol, United Kingdom, were included. Child
      and parent TV viewing were self-reported and categorized as <2, 2 to 4, or >4
      hours/day. Children reported maternal parenting style (authoritarian,
      authoritative, or permissive). Child-reported maternal and paternal sedentary
      restriction scores were combined to create a family-level restriction score.
      Multinomial logistic regression was used to examine whether child TV viewing was
      predicted by parenting style or family restriction. RESULTS: A greater proportion
      of children with permissive mothers watched >4 hours of TV per day, compared with
      children with authoritarian or authoritative mothers (P = .033). A greater
      proportion of children for whom both parents demonstrated high restriction
      watched <2 hours of TV per day (P < .001). The risk of watching 2 to 4 hours (vs
      <2 hours) of TV per day was 2.2 times higher for children from low-restriction
      families (P = .010). The risk of watching >4 hours (vs <2 hours) of TV per day
      was 3.3 times higher for children from low-restriction families (P = .013). The
      risk of watching >4 hours of TV per day was 5.2 times higher for children with
      permissive (versus authoritative) mothers (P = .010). CONCLUSIONS: Clinicians
      need to talk directly with parents about the need to place limitations on
      children's screen time and to encourage both parents to reinforce restriction
      messages.

PMID- 21859911
TI  - Universal hepatitis B vaccination reduces childhood hepatitis B virus-associated
      membranous nephropathy.
AB  - OBJECTIVE: To compare the incidence of hepatitis B virus (HBV)-associated
      membranous nephropathy (HBVMN) before and after universal HBV vaccination and to
      identify factors underlying the change. METHODS: This study included 471
      hospitalized children with nephrotic syndrome (NS) and 488 long-term follow-up
      hepatitis B surface antigen (HBsAg)-carrier children. Horizontal transmission
      (negative maternal HBsAg status) of HBVMN and HBV was assessed, and the incidence
      of HBVMN was compared before and after initiation of the universal HBV
      vaccination program started in 1984. RESULTS: The frequency of HBVMN in children
      with NS was 11.6% between 1974 and 1984, 4.5% between 1984 and 1994, 2.1% between
      1994 and 2004, and 0% between 2004 and 2009. Similarly, the number of HBsAg
      seropositive children with NS (mainly via horizontal infection) decreased after
      universal vaccination. The prevaccination frequency of HBV horizontal
      transmission in chronic HBsAg carriers from the general population was 36.5%
      compared with 5% in the postvaccination period. The incidence of HBVMN in these
      carriers revealed a parallel decline. CONCLUSIONS: Our results revealed a
      significant decrease in the frequency of HBVMN in children with NS and in long
      term follow-up HBsAg carriers. Children with HBVMN are primarily infected with
      HBV via horizontal transmission; thus, the significant reduction in horizontal
      transmission in HBsAg-carrier children in the general population after universal
      HBV vaccination may explain the reduction of HBVMN in the vaccinated population.
      These findings confirm the effectiveness of HBV vaccination on reducing the
      incidence of HBVMN, possibly through a significant decline in horizontal HBV
      infection.

PMID- 21859912
TI  - Clinical prediction rules for children: a systematic review.
AB  - CONTEXT: The degree to which clinical prediction rules (CPRs) for children meet
      published standards is unclear. OBJECTIVE: To systematically review the quality,
      performance, and validation of published CPRs for children, compare them with
      adult CPRs, and suggest pediatric-specific changes to CPR methodology. METHODS:
      Medline was searched from 1950 to 2011. Studies were selected if they included
      the development of a CPR involving children younger than 18 years. Two
      investigators assessed study quality, rule performance, and rule validation as
      methodologic standards. RESULTS: Of 7298 titles and abstracts assessed, 137
      eligible studies were identified. They describe the development of 101 CPRs
      addressing 36 pediatric conditions. Quality standards met in fewer than half of
      the studies were blind assessment of predictors (47%), reproducibility of
      predictors (18%), blind assessment of outcomes (42%), adequate follow-up of
      outcomes (36%), adequate power (43%), adequate reporting of results (49%), and
      95% confidence intervals reported (36%). For rule performance, 48% had a
      sensitivity greater than 0.95, and 43% had a negative likelihood ratio less than
      0.1. For rule validation, 76% had no validation, 17% had narrow validation, 8%
      had broad validation, and none had impact analysis performed. Compared with CPRs
      for adult health conditions, quality and rule validation seem to be lower.
      CONCLUSIONS: Many CPRs have been derived for children, but few have been
      validated. Relative to adult CPRs, several quality indicators demonstrated
      weaknesses. Existing performance standards may prove elusive for CPRs that
      involve children. CPRs for children that are more assistive and less directive
      and include patients' values and preferences in decision-making may be helpful.

PMID- 21859913
TI  - Specific celiac disease antibodies in children on a gluten-free diet.
AB  - OBJECTIVE: Celiac disease (CD) is characterized by histologic alterations in
      small bowel biopsies. Circulating specific CD antibodies at the time of diagnosis
      and their disappearance after a gluten-free diet support the diagnosis of CD. We
      aimed to determine the behavior of the CD antibodies immunoglobulin A anti-tissue
      transglutaminase (anti-TG2) and immunoglobulin A endomysium (EMA) in children
      with CD after starting a gluten-free diet. METHODS: This was a retrospective
      multicenter study in the Netherlands between 2001 and 2009. Inclusion criteria
      were all newly diagnosed patients with CD younger than 19 years who had at least
      1 anti-TG2 and/or EMA measurement before and after starting a gluten-free diet.
      Eight different anti-TG2 kits were used with substrates of guinea pig TG2 in 1
      (Sigma) and 7 human-recombinant TG2: Varelisa and EliA Celikey Phadia-GmbH;
      Orgentec Diagnostica-GmbH; Diarect AG; Roboscreen GmbH; Aeskulisa Diagnostics;
      Binding Site Ltd. EMA was analyzed with indirect immunofluorescence tests.
      Statistical analyses were performed by using mixed-model repeated measurements
      and survival analysis. RESULTS: There were 129 children with CD included (mean
      age: 5.6 years; SD +/- 4.2). The mean concentration of anti-TG2 decreased
      significantly within 3 months after starting a gluten-free diet (P < .0001). The
      cumulative percentage of children who became negative for EMA after 1/2, 1, 11/2,
      and 2 years was 31%, 60%, 74%, and 87%, respectively. For anti-TG2, a comparable
      trend was shown: 35%, 55%, 64%, and 78%, respectively. CONCLUSIONS: Doctors
      taking care of children with CD should be aware that the mean concentration of
      anti-TG2 will show a 74% decrease (95% confidence interval: 69%-79%) after 3
      months of gluten-free diet, and ~80% of the children will be sero-negative for
      EMA and anti-TG2 after 2 years of the diet.

PMID- 21859915
TI  - Written-language disorder among children with and without ADHD in a population
      based birth cohort.
AB  - OBJECTIVE: We determined the incidence of written-language disorder (WLD) among
      children with and without attention-deficit/hyperactivity disorder (ADHD) in a
      population-based birth cohort. METHODS: Subjects included a birth cohort of all
      children born in 1976-1982 who remained in Rochester, Minnesota, after 5 years of
      age (N = 5718). Information from medical, school, and private tutorial records
      was abstracted. Cumulative incidences of WLD with or without reading disability
      (RD), identified with any of 3 formulas, among children with and without ADHD and
      hazard ratios (HRs) were calculated. RESULTS: For both genders, the cumulative
      incidence of WLD by 19 years of age was significantly higher for children with
      ADHD than for children without ADHD (boys: 64.5% vs 16.5%; girls: 57.0% vs 9.4%).
      The magnitude of association between ADHD and WLD with RD was significantly
      higher for girls than for boys (adjusted HR: girls: 9.8; boys: 4.2; P < .001).
      However, this was not true for WLD without RD (adjusted HR: girls: 7.4; boys:
      6.6; P = .64). CONCLUSIONS: ADHD is strongly associated with an increased risk of
      WLD (with or without RD) for both boys and girls. Girls with ADHD are at higher
      risk of having WLD with RD compared with boys with ADHD, whereas boys and girls
      are at the same risk of having WLD without RD.

PMID- 21859916
TI  - Quality of reporting of neonatal and infant trials in high-impact journals.
AB  - OBJECTIVES: To perform a systematic review of the quality of reporting for
      randomized controlled trials (RCTs) with infants and neonates that were published
      in high-impact journals and to identify RCT characteristics associated with
      quality of reporting. METHODS: RCTs that enrolled infants younger than 12 months
      and were published in 2005-2009 in 6 pediatric or general medical journals were
      reviewed. Eligible RCTs were evaluated for the presence of 11 quality criteria
      selected from the Consolidated Standards of Reporting Trials guidelines. The
      relationships between quality of reporting and key study characteristics were
      tested with nonparametric statistics. RESULTS: Two reviewers had very good
      agreement regarding the eligibility of studies (kappa = 0.85) and the presence of
      quality criteria (kappa = 0.82). Among 179 eligible RCTs, reporting of the
      individual quality criteria varied widely. Only 50% included a flow diagram, but
      99% reported the number of study participants. Higher quality of reporting was
      associated with greater numbers of study participants, publication in a general
      medical journal, and greater numbers of centers (P < .0001 for each comparison).
      Geographic region and positive study outcomes were not associated with reporting
      quality. CONCLUSIONS: The quality of reporting of infant and neonatal RCTs is
      inconsistent, particularly in pediatric journals. Therefore, readers cannot
      assess accurately the validity of many RCT results. Strict adherence to the
      Consolidated Standards of Reporting Trials guidelines should lead to improved
      reporting.

PMID- 21859917
TI  - Potential for liver and kidney donation after circulatory death in infants and
      children.
AB  - OBJECTIVE: To determine the potential effect of organ donation after circulatory
      death (DCD) on the number of kidney and liver donors in a PICU. PATIENTS AND
      METHODS: All deaths in the PICU of an academic, tertiary care children's hospital
      from May 1996 to April 2007 were retrospectively reviewed. Patient demographics,
      premortem physiology, and end-of-life circumstances were recorded and compared
      with basic criteria for potential organ donation. A sensitivity analysis was
      performed to examine the effect of more strict physiologic and time criteria as
      well as 3 different rates of consent for donation. RESULTS: There were 1389
      deaths during 11 years; 634 children (46%) underwent withdrawal of life support,
      of whom 518 had complete data and were analyzed. There were 131 children (25% of
      those withdrawn, 9% of all deaths) who met basic physiologic and time criteria
      for organ donation (80 kidney; 107 liver). Consideration of consent rates in
      sensitivity analysis resulted in an estimated 24 to 85 organ donors, an increase
      of 28% to 99% over the 86 actual brain-dead donors during the same time period.
      Assuming historical rates of organ recovery, these DCD donors might have produced
      30 to 88 additional kidneys and 8 to 56 additional livers, an increase of 21% to
      60% in kidney donation and 13% to 80% in livers above the number of organs
      recovered from brain-dead donors. CONCLUSIONS: Although relatively few children
      may have been eligible for DCD, they might have increased the number of organ
      donors from our institution, depending greatly on consent rates. DCD merits
      additional discussion and exploration.

PMID- 21859914
TI  - Adherence to guidelines for youths with diabetes mellitus.
AB  - OBJECTIVE: To describe demographic and clinical characteristics associated with
      self-reported receipt of tests and measurements recommended by the American
      Diabetes Association (ADA) for children and youths with diabetes. METHODS: The
      study included 1514 SEARCH for Diabetes in Youth study participants who completed
      a survey about diabetes care received. Quality-of-care measures were based on ADA
      guidelines for eye examinations and glycohemoglobin (hemoglobin A1c [HbA1c]),
      lipid level, microalbuminuria, and blood pressure measurements, and a composite
      variable of these 5 indicators was created. Multivariate logistic regression
      models were used to assess the association of selected demographic and clinical
      characteristics with the reported receipt of all recommended tests and
      measurements according to age and diabetes type subgroups. RESULTS: Overall, 95%
      of the participants reported having their blood pressure checked at all or most
      visits, 88% had lipid levels measured, 83% had kidney function tested, 68%
      underwent HbA1c testing, and 66% underwent an eye examination, in accordance with
      ADA recommendations. Participants aged 18 years or older, particularly those with
      type 2 diabetes, tended to have fewer tests of all kinds performed. Age and
      family income emerged as important correlates of overall quality of care in
      multivariate models; older age and lower income were associated with not meeting
      guidelines. CONCLUSIONS: Although there was relatively good adherence to ADA
      recommended guidelines for most indicators, efforts are needed to improve rates
      of HbA1c testing and eye examinations, particularly among older youths.

PMID- 21859918
TI  - Ethnic variability in persistent asthma after in utero tobacco exposure.
AB  - BACKGROUND: The effects of in utero tobacco smoke exposure on childhood
      respiratory health have been investigated, and outcomes have been inconsistent.
      OBJECTIVE: To determine if in utero tobacco smoke exposure is associated with
      childhood persistent asthma in Mexican, Puerto Rican, and black children.
      PATIENTS AND METHODS: There were 295 Mexican, Puerto Rican, and black asthmatic
      children, aged 8 to 16 years, who underwent spirometry, and clinical data were
      collected from the parents during a standardized interview. The effect of in
      utero tobacco smoke exposure on the development of persistent asthma and related
      clinical outcomes was evaluated by logistic regression. RESULTS: Children with
      persistent asthma had a higher odds of exposure to in utero tobacco smoke, but
      not current tobacco smoke, than did children with intermittent asthma (odds ratio
      [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years
      of life did not alter this association. Furthermore, there were higher odds of in
      utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR:
      2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency
      department visits (OR: 3.85; P = .015) within the year. CONCLUSIONS: Exposure to
      tobacco smoke in utero was significantly associated with persistent asthma among
      Mexican, Puerto Rican, and black children compared with those with intermittent
      asthma. These results suggest that smoking cessation during pregnancy may lead to
      a decrease in the incidence of persistent asthma in these populations.

PMID- 21859919
TI  - Parent involvement in pain management for NICU infants: a randomized controlled
      trial.
AB  - OBJECTIVES: To demonstrate feasibility and estimate the effect of an intervention
      to increase parental involvement in infant pain management in the NICU on
      parents' stress and postdischarge parenting competence and confidence. METHODS:
      The study involved a randomized controlled trial. Parents recruited from 4 NICUs
      were randomly assigned by site to receive (1) a pain information booklet and
      instruction on infant comforting techniques (n = 84 intervention) in addition to
      a generic NICU care booklet or (2) the generic NICU care booklet alone (n = 85
      control). The primary outcome was postintervention Parent Stressor Scale: NICU
      (PSS:NICU) scores. Secondary outcomes included parent attitudes about infant
      pain, nursing pain assessment, and parenting competence and role attainment after
      discharge. RESULTS: No differences were found between groups in PSS:NICU scores.
      Significant differences favoring the intervention group were found for
      satisfaction with pain information, parents shown infant pain cues and comforting
      techniques, nursing pain assessment, and parent preference for involvement during
      painful procedures. Role attainment after discharge was higher for the
      intervention group than for the control group. Both the intervention and control
      groups highly valued attention to infant pain and wanted information and
      involvement. CONCLUSIONS: These results provide no evidence of a reduction in
      NICU-related stress for parents who receive an intervention to increase their
      understanding and involvement in infant pain management. However, parents in the
      intervention group were better prepared to take an active role in infant pain
      care and had more positive views about their role attainment in the postdischarge
      period.

PMID- 21859920
TI  - The walking school bus and children's physical activity: a pilot cluster
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the impact of a "walking school bus" program on children's
      rates of active commuting to school and physical activity. METHODS: We conducted
      a pilot cluster randomized controlled trial among 4th-graders from 8 schools in
      Houston, Texas (N = 149). Random allocation to treatment or control conditions
      was at the school level. Study staff walked with children to and from school up
      to 5 days/week. Outcomes were measured the week before (time 1) and during weeks
      4 and 5 of the intervention (time 2). The main outcome was the weekly rate of
      active commuting, and a secondary outcome was moderate-to-vigorous physical
      activity. Covariates included sociodemographics, distance from home to school,
      neighborhood safety, child BMI z score, parent self-efficacy/outcome
      expectations, and child self-efficacy for active commuting. A mixed-model
      repeated measures regression accounted for clustering by school, and stepwise
      procedures with backward elimination of nonsignificant covariates were used to
      identify significant predictors. RESULTS: Intervention children increased active
      commuting (mean +/- SD) from 23.8% +/- 9.2% (time 1) to 54% +/- 9.2% (time 2),
      whereas control subjects decreased from 40.2% +/- 8.9% (time 1) to 32.6% +/- 8.9%
      (time 2) (P < .0001). Intervention children increased their minutes of daily
      moderate-to-vigorous physical activity from 46.6 +/- 4.5 (time 1) to 48.8 +/- 4.5
      (time 2), whereas control children decreased from 46.1 +/- 4.3 (time 1) to 41.3
      +/- 4.3 (time 2) (P = .029). CONCLUSIONS: The program improved children's active
      commuting to school and daily moderate-to-vigorous physical activity.

PMID- 21859922
TI  - Transcultural nursing scholars' corner: advancing our practice, changing our
      world.

PMID- 21859921
TI  - Decisions of black parents about infant bedding and sleep surfaces: a qualitative
      study.
AB  - OBJECTIVE: The goal of this qualitative study was to examine factors influencing
      decisions by black parents regarding use of soft bedding and sleep surfaces for
      their infants. METHODS: We conducted focus groups and individual interviews with
      black mothers of lower and higher socioeconomic status (SES). Mothers were asked
      about many infant care practices, including sleep surface and bedding. RESULTS:
      Eighty-three mothers were interviewed, 73 (47 lower and 26 higher SES) in focus
      groups and 10 (7 lower and 3 higher SES) in individual interviews. The primary
      reason for using soft surfaces was infant comfort. Parents perceived that infants
      were uncomfortable if the surface was not soft. Many parents also interpreted
      "firm sleep surface" to mean taut; they were comfortable with and believed that
      they were following recommendations for a firm sleep surface when they placed
      pillows/blankets on the mattress as long as a sheet was pulled tautly over the
      pillows/blankets. The primary reasons for using soft bedding (including bumper
      pads) were comfort, safety, and aesthetics. In addition to using bedding to
      soften sleep surfaces, bedding was used to prevent infant rollover and falls,
      particularly for infants sleeping on a bed or sofa. Some parents used soft
      bedding to create an attractive space for the infant. CONCLUSIONS: Many black
      parents believe that soft bedding will keep their infant safe and comfortable.
      There is much misunderstanding about the meaning of a "firm" sleep surface.
      Additional educational messages apparently are needed to change parental
      perceptions and practices.

PMID- 21859923
TI  - African American women and weight loss: disregarding environmental challenges.
AB  - In the United States, almost 80% of African American women are either overweight
      or obese. In this study, 46 low-income African American women struggling with
      weight issues participated in structured interviews using a social cognitive
      theory framework. Participants shared their social cognitive theory related
      weight loss thoughts and their perceived weight loss obstacles. Results suggest
      that although participants' primary weight-related obstacles were environment
      based, for example, unsafe environments in which to engage in regular exercise,
      they more often offered individual-based solutions. The study concludes with a
      discussion of media advocacy as a tool that can be used to promote environmental
      solutions.

PMID- 21859924
TI  - President's message: peer pressure . . . the best kind!

PMID- 21859925
TI  - Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta
      carotene cancer prevention study.
AB  - Diabetes, obesity, and cigarette smoke, consistent risk factors for pancreatic
      cancer, are sources of oxidative stress in humans that could cause mitochondrial
      DNA (mtDNA) damage and increase mtDNA copy number. To test whether higher mtDNA
      copy number is associated with increased incident pancreatic cancer, we conducted
      a nested case-control study in the Alpha-Tocopherol Beta Carotene Cancer
      Prevention (ATBC) Study cohort of male smokers, aged 50 to 69 years at baseline.
      Between 1992 and 2004, 203 incident cases of pancreatic adenocarcinoma occurred
      (follow-up: 12 years) among participants, with whole blood samples used for mtDNA
      extraction. For these cases and 656 controls, we calculated ORs and 95% CIs using
      unconditional logistic regression, adjusting for age, smoking, and diabetes
      history. All statistical tests were two sided. Higher mtDNA copy number was
      significantly associated with increased pancreatic cancer risk (highest vs.
      lowest mtDNA copy number quintile, OR = 1.64, 95% CI = 1.01-2.67, continuous OR =
      1.14, 95% CI 1.06-1.23), particularly for cases diagnosed during the first 7
      years of follow-up (OR = 2.14, 95% CI = 1.16-3.96, P(trend) = 0.01, continuous OR
      = 1.21, 95% CI = 1.10-1.33), but not for cases occurring during follow-up of 7
      years or greater (OR = 1.14, 95% CI = 0.53-2.45, continuous OR = 1.05, 95% CI =
      0.93-1.18). Our results support the hypothesis that mtDNA copy number is
      associated with pancreatic cancer and could possibly serve as a biomarker for
      pancreatic cancer development.

PMID- 21859926
TI  - Knockdown of survivin (BIRC5) causes apoptosis in neuroblastoma via mitotic
      catastrophe.
AB  - BIRC5 (survivin) is one of the genes located on chromosome arm 17q in the region
      that is often gained in neuroblastoma. BIRC5 is a protein in the intrinsic
      apoptotic pathway that interacts with XIAP and DIABLO leading to caspase-3 and
      caspase-9 inactivation. BIRC5 is also involved in stabilizing the microtubule
      kinetochore dynamics. Based on the Affymetrix mRNA expression data, we here show
      that BIRC5 expression is strongly upregulated in neuroblastoma compared with
      normal tissues, adult malignancies, and non-malignant fetal adrenal neuroblasts.
      The over-expression of BIRC5 correlates with an unfavorable prognosis independent
      of the presence of 17q gain. Silencing of BIRC5 in neuroblastoma cell lines by
      various antisense molecules resulted in massive apoptosis as measured by PARP
      cleavage and FACS analysis. As both the intrinsic apoptotic pathway and the
      chromosomal passenger complex can be therapeutically targeted, we investigated in
      which of them BIRC5 exerted its essential anti-apoptotic role. Immunofluorescence
      analysis of neuroblastoma cells after BIRC5 silencing showed formation of
      multinucleated cells indicating mitotic catastrophe, which leads to apoptosis via
      P53 and CASP2. We show that BIRC5 silencing indeed resulted in activation of P53
      and we could rescue apoptosis by CASP2 inhibition. We conclude that BIRC5
      stabilizes the microtubules in the chromosomal passenger complex in neuroblastoma
      and that the apoptotic response results from mitotic catastrophe, which makes
      BIRC5 an interesting target for therapy.

PMID- 21859927
TI  - The role of microRNA deregulation in the pathogenesis of adrenocortical
      carcinoma.
AB  - Adrenocortical carcinoma (ACC) is an aggressive tumor showing frequent metastatic
      spread and poor survival. Although recent genome-wide studies of ACC have
      contributed to our understanding of the disease, major challenges remain for both
      diagnostic and prognostic assessments. The aim of this study was to identify
      specific microRNAs (miRNAs) associated with malignancy and survival of ACC
      patients. miRNA expression profiles were determined in a series of ACC, adenoma,
      and normal cortices using microarray. A subset of miRNAs showed distinct
      expression patterns in the ACC compared with adrenal cortices and adenomas. Among
      others, miR-483-3p, miR-483-5p, miR-210, and miR-21 were found overexpressed,
      while miR-195, miR-497, and miR-1974 were underexpressed in ACC. Inhibition of
      miR-483-3p or miR-483-5p and overexpression of miR-195 or miR-497 reduced cell
      proliferation in human NCI-H295R ACC cells. In addition, downregulation of miR
      483-3p, but not miR-483-5p, and increased expression of miR-195 or miR-497 led to
      significant induction of cell death. Protein expression of p53 upregulated
      modulator of apoptosis (PUMA), a potential target of miR-483-3p, was
      significantly decreased in ACC, and inversely correlated with miR-483-3p
      expression. In addition, high expression of miR-503, miR-1202, and miR-1275 were
      found significantly associated with shorter overall survival among patients with
      ACC (P values: 0.006, 0.005, and 0.042 respectively). In summary, we identified
      additional miRNAs associated with ACC, elucidated the functional role of four
      miRNAs in the pathogenesis of ACC cells, demonstrated the potential involvement
      of the pro-apoptotic factor PUMA (a miR-483-3p target) in adrenocortical tumors,
      and found novel miRNAs associated with survival in ACC.

PMID- 21859928
TI  - Negative transfer in human associative learning.
AB  - Models of attentional allocation in associative learning are typically structured
      according to one of two guiding principles: the predictiveness principle, which
      posits that attention is paid to cues that have reliably predicted an outcome in
      the past, or the uncertainty principle, which states that attention is paid to
      cues about which little is known. Both principles are well supported by studies
      of animals. However, in studies of human learning, there is very little direct
      empirical support for the uncertainty principle. In the study reported here, we
      addressed this gap by investigating negative transfer, a phenomenon that may
      provide unique support for the uncertainty principle. In two human learning
      experiments using an allergist task, we replicated the primary findings of
      previous research on animal learning. We believe that these data provide the
      first direct evidence for the uncertainty principle in human associative
      learning.

PMID- 21859930
TI  - Mimics of the dimerization domain of hepatocyte growth factor exhibit anti-Met
      and anticancer activity.
AB  - The angiotensin IV analog norleual [Nle-Tyr-Leu-psi-(CH(2)-NH(2))-Leu-His-Pro
      Phe] has been shown recently to act as a hepatocyte growth factor (HGF)/Met
      antagonist capable of blocking the binding of HGF to the Met receptor, inhibiting
      HGF-dependent activation of Met, and attenuating HGF-dependent cellular
      activities. In addition, norleual exhibited marked anticancer activity. Homology
      between norleual and the dimerization domain (hinge region) of HGF led to the
      hypothesis that norleual acts by interfering with HGF
      dimerization/multimerization and functions as a dominant-negative hinge region
      mimic. To test this hypothesis we investigated the ability of norleual to bind to
      and inhibit the dimerization of HGF. To further evaluate the idea that norleual
      was acting as a hinge region mimic, we synthesized a hexapeptide representing the
      HGF hinge sequence and established its capacity to similarly block HGF-dependent
      activation of Met and HGF-dependent cellular functions. The hinge peptide not
      only bound with high affinity directly to HGF and blocked its dimerization but it
      also inhibited HGF-dependent Met activation, suppressed HGF-dependent cellular
      functions, and exhibited anticancer activity. The major implication of this study
      is that molecules targeting the dimerization domain of HGF may represent novel
      and viable anticancer therapeutic agents; the development of such molecules
      should be feasible using norleual and the hinge peptide as synthetic templates.

PMID- 21859929
TI  - Decreases in cocaine self-administration with dual inhibition of the dopamine
      transporter and sigma receptors.
AB  - Sigma receptor (sigmaR) antagonists attenuate many behavioral effects of cocaine
      but typically not its reinforcing effects in self-administration procedures.
      However, the sigmaR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis
      3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride
      (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)
      propyl]carbazole hydrobromide (SH 3-28), dose-dependently decreased the maximal
      rates of cocaine self-administration without affecting comparable responding
      maintained by food reinforcement. In contrast, a variety of sigmaR antagonists [N
      phenethylpiperidine oxalate (AC927), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2
      (1-pyrrolidinyl)ethylamine dihydrobromide (BD 1008), N-[2-(3,4
      dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD
      1047), N-[2-(3,4-dichlorophenyl) ethyl]-4-methylpiperazine dihydrochloride (BD
      1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine
      monohydrochloride (NE-100)] had no effect on cocaine self-administration across
      the range of doses that decreased rates of food-maintained responding. Rimcazole
      analogs differed from selective sigmaR antagonists in their dual affinities for
      sigmaRs and the dopamine transporter (DAT) assessed with radioligand binding.
      Selective DAT inhibitors and sigmaR antagonists were studied alone and in
      combination on cocaine self-administration to determine whether actions at both
      sigmaRs and the DAT were sufficient to reproduce the effects of rimcazole
      analogs. Typical DAT inhibitors [2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane
      (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the
      cocaine dose-effect curve leftward. Combinations of DAT inhibitor and sigmaR
      antagonist doses that were behaviorally inactive alone decreased cocaine self
      administration without effects on food-maintained responding. In addition,
      whereas the DAT inhibitors were self-administered at rates similar to those of
      cocaine, neither rimcazole analogs nor typical sigmaR antagonists (NE-100 and
      AC927) maintained responding above control levels across a wide range of doses.
      These findings suggest that the unique effects of rimcazole analogs are due to
      dual actions at the DAT and sigmaRs and that a combined target approach may have
      utility in development of medical treatments for cocaine abuse.

PMID- 21859931
TI  - Differential effects of nociceptin/orphanin FQ (NOP) receptor agonists in acute
      versus chronic pain: studies with bifunctional NOP/MU receptor agonists in the
      sciatic nerve ligation chronic pain model in mice.
AB  - 1-(1-Cyclooctylpiperidin-4-yl)-indolin-2-one (SR14150) and 1-(1-(2,3,3a,4,5,6
      hexahydro-1H-phenalen-1-yl)piperidinl-4-yl)-indolin-2-one (SR16835) are
      moderately selective nociceptin/orphanin FQ (NOP) receptor agonists. In the
      [(35)S]guanosine 5'-O-(3-thiotriphosphate) assay in vitro, SR14150 is a partial
      agonist at both the NOP and MU-opioid receptors, whereas SR16835 is a full
      agonist at the NOP receptor and has low efficacy at MU receptors. These compounds
      were tested for antinociceptive and antiallodynic activity, using mice in chronic
      pain, subsequent to spinal nerve ligation (SNL) surgery. When administered
      subcutaneously to mice after SNL surgery, SR14150 but not SR16835 increased tail
      flick latency, which was blocked by the opioid antagonist naloxone, but not by
      the NOP receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin
      1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). In
      contrast, both SR14150 and SR16835 had antiallodynic activity when mechanical
      allodynia was measured with von Frey monofilaments. This effect was completely
      blocked by SB-612111 but not by naloxone. On the other hand, morphine
      antinociception and antiallodynia were both blocked by naloxone and potentiated
      by SB-612111. These results indicate that, in mice, circuitry mediating
      antinociceptive activity in acute and chronic pain states is different. It is
      possible that during a chronic pain state, an up-regulated NOP system in the
      spinal cord leads to NOP receptor-mediated antiallodynia, which is blocked by NOP
      antagonists. However, supraspinal up-regulation could lead to an attenuation of
      morphine antinociception and antiallodynia, which can be alleviated by an NOP
      receptor antagonist. Thus, although neither NOP agonists nor antagonists are
      effective as analgesics in acute pain, they may have efficacy as analgesics,
      either alone or in combination with morphine, for treatment of chronic pain.

PMID- 21859932
TI  - Comparison of azithromycin pharmacokinetics following single oral doses of
      extended-release and immediate-release formulations in children with acute otitis
      media.
AB  - An azithromycin extended-release (ER) oral suspension was developed to improve
      the gastrointestinal tolerability profile without substantially compromising
      systemic exposure. A single dose of 30 mg/kg azithromycin immediate-release (IR)
      oral suspension has been used in children to treat acute otitis media (AOM). This
      study was conducted to compare the pharmacokinetics of a 60-mg/kg azithromycin ER
      single dose with a 30-mg/kg azithromycin IR single dose in children with AOM aged
      6 months to 6 years (n = 19 per treatment). Serum samples were collected at 1, 2,
      3, 4, 8, 24, 48, and 72 h after dosing. The area under the curve from time zero
      to 72 h postdosing (AUC(0-72)) was calculated based on a noncompartmental method.
      One-way analysis of variance (ANOVA) was used to compare exposure parameters
      (e.g., AUC(0-72) and peak concentration) as well as concentrations at each time
      point. The adjusted geometric mean ratio of the ER/IR AUC(0-72) was 157.98% (90%
      confidence interval [CI], 98.87%, 252.44%), which met the predefined criterion of
      the lower boundary of the 90% CI of >= 80%. As expected, due to the slower
      release profile of the ER formulation, the concentrations of the ER formulation
      during the first 3 h were lower than those of the IR formulation. After 3 h
      postdosing, the lower boundaries of the 90% CI for the ER/IR concentration ratios
      were greater than 100%. These results indicated that a 60-mg/kg single dose of ER
      azithromycin provides similar or greater systemic exposure in children than the
      30-mg/kg single dose of IR azithromycin.

PMID- 21859933
TI  - Genetic features of blaNDM-1-positive Enterobacteriaceae.
AB  - Genetic features associated with the bla(NDM-1) gene were investigated in 6
      Escherichia coli, 7 Klebsiella pneumoniae, 1 Citrobacter freundii, 1 Proteus
      mirabilis, and 1 Providencia stuartii isolate of worldwide origin. Clonal
      diversity was observed for both E. coli and K. pneumoniae. The bla(NDM-1) gene
      was carried by different plasmid types (IncA/C, IncF, IncL/M, or untypeable) and
      was likely chromosome borne in two isolates. The bla(NDM-1) plasmids coharbored a
      variety of resistance determinants, including beta-lactamase genes, quinolone
      resistance genes, and 16S RNA methylase genes.

PMID- 21859934
TI  - Environmental microbiota represents a natural reservoir for dissemination of
      clinically relevant metallo-beta-lactamases.
AB  - A total of 10 metallo-beta-lactamase-producing isolates of six different species,
      including Brevundimonas diminuta (n = 3), Rhizobium radiobacter (n = 2),
      Pseudomonas monteilii (n = 1), Pseudomonas aeruginosa (n = 2), Ochrobactrum
      anthropi (n = 1), and Enterobacter ludwigii (n = 1), were detected in the sewage
      water of a hospital. The presence of bla(VIM-13) associated with a Tn1721-class 1
      integron structure was detected in all but one of the isolates (E. ludwigii,
      which produced VIM-2), and in two of them (R. radiobacter), this structure was
      located on a plasmid, suggesting that environmental bacteria represent a
      reservoir for the dissemination of clinically relevant metallo-beta-lactamase
      genes.

PMID- 21859935
TI  - Recombination in IS26 and Tn2 in the evolution of multiresistance regions
      carrying blaCTX-M-15 on conjugative IncF plasmids from Escherichia coli.
AB  - CTX-M-15 now appears to be the dominant extended-spectrum beta-lactamase
      worldwide, and a number of different factors may contribute to this success.
      These include associations between bla(CTX-M-15) and particular plasmids (IncF)
      and/or strains, such as Escherichia coli ST131, as well as the genetic contexts
      in which this gene is found. We previously identified bla(CTX-M-15) as the
      dominant ESBL gene in the western Sydney area, Australia, and found that it was
      carried mainly on IncF or IncI1 plasmids. Here, we have mapped the
      multiresistance regions of the 11 conjugative plasmids with one or more IncF
      replicons obtained from that survey and conducted a limited comparison of plasmid
      backbones. Two plasmids with only an IncFII replicon appear to be very similar to
      the published plasmids pC15-1a and pEK516. The remaining nine plasmids, with
      multiple IncF replicons, have multiresistance regions related to those of pC15-1a
      and pEK516, but eight contain additional modules previously found in resistance
      plasmids from different geographic locations that carry a variety of different
      resistance genes. Differences between the multiresistance regions are largely due
      to IS26-mediated deletions, insertions, and/or rearrangements, which can explain
      the observed variable associations between bla(CTX-M-15) and certain other
      resistance genes. We found no evidence of independent movement of bla(CTX-M-15)
      or of a large multiresistance region between different plasmid backbones.
      Instead, homologous recombination between common components, such as IS26 and
      Tn2, appeared to be more important in creating new multiresistance regions, and
      this may be coupled with recombination in plasmid backbones to reassort multiple
      IncF replicons as well as components of multiresistance regions.

PMID- 21859936
TI  - Meningeal inflammation increases artemether concentrations in cerebrospinal fluid
      in Papua New Guinean children treated with intramuscular artemether.
AB  - Although the artemisinin-associated neurotoxicity identified in vitro and in
      animal studies has not been confirmed clinically, only one adult study has
      measured cerebrospinal fluid (CSF) concentrations after administration of
      conventional doses. Potential artemisinin neurotoxicity could be serious in
      children, especially those with meningitis and, consequently, a compromised blood
      brain barrier. We measured CSF/plasma artemether and dihydroartemisinin (DHA)
      concentrations in 32 Papua New Guinean children with a mean age of 39 months with
      suspected or proven severe falciparum malaria who underwent a single lumbar
      puncture after intramuscular artemether administration. CSF artemether
      concentrations were 0 to 43.5 MUg/liter and CSF concentration/plasma
      concentration ratios were 0 to 38.1%. DHA was measurable in CSF in only two
      children. The seven children with meningeal inflammation (CSF white cell count >
      20/mm(3)) had higher CSF artemether concentration/plasma artemether concentration
      ratios than those without (median, 6.7% [interquartile ratio, 2.5 to 27.8%]%
      versus 0.0% [interquartile ratio, 0.0 to 2.5%]; P = 0.002). Meningeal
      inflammation was associated with a 4.6-fold increase in the CSF artemether
      concentration/plasma artemether concentration ratio in a population
      pharmacokinetic model. These data suggest that pharmacovigilance should be
      heightened when intramuscular artemether is given to severely ill children with
      evidence of meningeal inflammation.

PMID- 21859937
TI  - ArmA methyltransferase in a monophasic Salmonella enterica isolate from food.
AB  - The 16S rRNA methyltransferase ArmA is a worldwide emerging determinant that
      confers high-level resistance to most clinically relevant aminoglycosides. We
      report here the identification and characterization of a multidrug-resistant
      Salmonella enterica subspecies I.4,12:i:- isolate recovered from chicken meat
      sampled in a supermarket on February 2009 in La Reunion, a French island in the
      Indian Ocean. Susceptibility testing showed an unusually high-level resistance to
      gentamicin, as well as to ampicillin, expanded-spectrum cephalosporins and
      amoxicillin-clavulanate. Molecular analysis of the 16S rRNA methyltransferases
      revealed presence of the armA gene, together with bla(TEM-1), bla(CMY-2), and
      bla(CTX-M-3). All of these genes could be transferred en bloc through conjugation
      into Escherichia coli at a frequency of 10(-5) CFU/donor. Replicon typing and S1
      pulsed-field gel electrophoresis revealed that the armA gene was borne on an ~150
      kb broad-host-range IncP plasmid, pB1010. To elucidate how armA had integrated in
      pB1010, a PCR mapping strategy was developed for Tn1548, the genetic platform for
      armA. The gene was embedded in a Tn1548-like structure, albeit with a deletion of
      the macrolide resistance genes, and an IS26 was inserted within the mel gene. To
      our knowledge, this is the first report of ArmA methyltransferase in food,
      showing a novel route of transmission for this resistance determinant. Further
      surveillance in food-borne bacteria will be crucial to determine the role of food
      in the spread of 16S rRNA methyltransferase genes worldwide.

PMID- 21859939
TI  - Plasma and tissue pharmacokinetics of cefazolin in patients undergoing elective
      and semielective abdominal aortic aneurysm open repair surgery.
AB  - Surgical site infections are common, so effective antibiotic concentrations at
      the sites of infection, i.e., in the interstitial fluid (ISF), are required. The
      aim of this study was to evaluate contemporary perioperative prophylactic dosing
      of cefazolin by determining plasma and subcutaneous ISF concentrations in
      patients undergoing elective/semielective abdominal aortic aneurysm (AAA) open
      repair surgery. This was a prospective pharmacokinetic study in a tertiary
      referral hospital. Cefazolin (2 g) was administered as a 3-min slow bolus 30 min
      prior to incision in 12 enrolled patients undergoing elective/semielective AAA
      open repair surgery. Serial blood, urine, and ISF (via microdialysis) samples
      were collected and analyzed using a validated liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method. Cardiac output was determined using pulse
      waveform contours with Vigileo. The recruited patients had a median
      (interquartile range) age of 70 (66 to 76) years and weight of 88 (81 to 95) kg.
      The median (interquartile range) terminal volume of distribution was 0.14 (0.11
      to 0.15) liter/kg, total clearance was 0.05 (0.03 to 0.06) liter/h, and minimum
      observed unbound concentration was 5.7 (5.4 to 8.1) mg/liter. The penetration of
      unbound drug from plasma to ISF was 85% (78% to 106%). We found correlations
      present, albeit weak, between cefazolin clearance and cardiac output (r(2) =
      0.11) and urinary creatinine clearance (r(2) = 0.12). In conclusion, we found
      that a single 2-g dose of cefazolin administered 30 min before incision provides
      plasma and ISF concentrations in excess of the likely MICs for susceptible
      pathogens in patients undergoing AAA open repair surgery.

PMID- 21859940
TI  - Efficacy of NZ2114, a novel plectasin-derived cationic antimicrobial peptide
      antibiotic, in experimental endocarditis due to methicillin-resistant
      Staphylococcus aureus.
AB  - Cationic antimicrobial peptides (CAPs) play important roles in host immune
      defenses. Plectasin is a defensin-like CAP isolated from the saprophytic fungus
      Pseudoplectania nigrella. NZ2114 is a novel variant of plectasin with potent
      activity against Gram-positive bacteria. In this study, we investigated (i) the
      in vivo pharmacokinetic and pharmacodynamic (PK/PD) characteristics of NZ2114 and
      (ii) the in vivo efficacy of NZ2114 in comparison with those of two conventional
      antibiotics, vancomycin or daptomycin, in an experimental rabbit infective
      endocarditis (IE) model due to a methicillin-resistant Staphylococcus aureus
      (MRSA) strain (ATCC 33591). All NZ2114 regimens (5, 10, and 20 mg/kg of body
      weight, intravenously [i.v.], twice daily for 3 days) significantly decreased
      MRSA densities in cardiac vegetations, kidneys, and spleen versus those in
      untreated controls, except in one scenario (5 mg/kg, splenic MRSA counts). The
      efficacy of NZ2114 was clearly dose dependent in all target tissues. At 20 mg/kg,
      NZ2114 showed a significantly greater efficacy than vancomycin (P < 0.001) and an
      efficacy similar to that of daptomycin. Of importance, only NZ2114 (in 10- and 20
      mg/kg regimens) prevented posttherapy relapse in cardiac vegetations, kidneys,
      and spleen, while bacterial counts in these target tissues continued to increase
      in vancomycin- and daptomycin-treated animals. These in vivo efficacies were
      equivalent and significantly correlated with three PK indices investigated:
      fC(max)/MIC (the maximum concentration of the free, unbound fraction of a drug in
      serum divided by the MIC), fAUC/MIC (where AUC is the area under the
      concentration-time curve), and f%T(>MIC) (%T(>MIC) is the cumulative percentage
      of a 24-h period that the drug concentration exceeds the MIC under steady-state
      pharmacokinetic conditions), as analyzed by a sigmoid maximum-effect (E(max))
      model (R(2) > 0.69). The superior efficacy of NZ2114 in this MRSA IE model
      suggests the potential for further development of this compound for treating
      serious MRSA infections.

PMID- 21859941
TI  - Dynamics of mutator and antibiotic-resistant populations in a
      pharmacokinetic/pharmacodynamic model of Pseudomonas aeruginosa biofilm
      treatment.
AB  - Biofilm growth, antibiotic resistance, and mutator phenotypes are key components
      of chronic respiratory infections by Pseudomonas aeruginosa in cystic fibrosis
      patients. We examined the dynamics of mutator and antibiotic-resistant
      populations in P. aeruginosa flow-cell biofilms, using fluorescently tagged PAO1
      and PAOMS (mutator [mutS] derivative) strains. Two-day-old biofilms were treated
      with ciprofloxacin (CIP) for 4 days (t4) at 2 MUg/ml, which correlated with the
      mutant prevention concentration (MPC) and provided an AUC/MIC ratio of 384 that
      should predict therapeutic success. Biofilms were monitored by confocal laser
      scanning microscopy (CLSM), and the numbers of viable cells and resistant mutants
      (4- and 16-fold MICs) were determined. Despite optimized
      pharmacokinetic/pharmacodynamic (PK/PD) parameters, CIP treatment did not
      suppress resistance development in P. aeruginosa biofilms. One-step resistant
      mutants (MexCD-OprJ or MexEF-OprN overexpression) were selected for both strains,
      while two-step resistant mutants (additional GyrA or GyrB mutation) were readily
      selected only from the mutator strain. CLSM analysis of competition experiments
      revealed that PAOMS, even when inoculated at a 0.01 proportion, took over the
      whole biofilm after only 2 days of CIP treatment outnumbering PAO1 by 3 log at
      t4. Our results show that mutational mechanisms play a major role in biofilm
      antibiotic resistance and that theoretically optimized PK/PD parameters fail to
      suppress resistance development, suggesting that the increased antibiotic
      tolerance driven by the special biofilm physiology and architecture may raise the
      effective MPC, favoring gradual mutational resistance development, especially in
      mutator strains. Moreover, the amplification of mutator populations under
      antibiotic treatment by coselection with resistance mutations is for the first
      time demonstrated in situ for P. aeruginosa biofilms.

PMID- 21859938
TI  - Carbapenems: past, present, and future.
AB  - In this review, we summarize the current "state of the art" of carbapenem
      antibiotics and their role in our antimicrobial armamentarium. Among the beta
      lactams currently available, carbapenems are unique because they are relatively
      resistant to hydrolysis by most beta-lactamases, in some cases act as "slow
      substrates" or inhibitors of beta-lactamases, and still target penicillin binding
      proteins. This "value-added feature" of inhibiting beta-lactamases serves as a
      major rationale for expansion of this class of beta-lactams. We describe the
      initial discovery and development of the carbapenem family of beta-lactams. Of
      the early carbapenems evaluated, thienamycin demonstrated the greatest
      antimicrobial activity and became the parent compound for all subsequent
      carbapenems. To date, more than 80 compounds with mostly improved antimicrobial
      properties, compared to those of thienamycin, are described in the literature. We
      also highlight important features of the carbapenems that are presently in
      clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem
      betamipron, and biapenem. In closing, we emphasize some major challenges and urge
      the medicinal chemist to continue development of these versatile and potent
      compounds, as they have served us well for more than 3 decades.

PMID- 21859942
TI  - Daptomycin, fosfomycin, or both for treatment of methicillin-resistant
      Staphylococcus aureus osteomyelitis in an experimental rat model.
AB  - The in vivo activities of daptomycin, fosfomycin, and a combination of both
      antibiotics against a clinical isolate of methicillin-resistant Staphylococcus
      aureus (daptomycin MIC, 0.25 MUg/ml; fosfomycin MIC, 0.5 MUg/ml) were evaluated
      in a rat model of osteomyelitis. A total of 37 rats with experimental
      osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of
      daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once
      daily, a combination of both drugs, or a saline placebo. After the completion of
      treatment, animals were euthanized, and the infected tibiae were processed for
      quantitative bacterial culture. Bone cultures were found to be positive for
      methicillin-resistant S. aureus in 9 of 9 (100%) animals of the placebo group, in
      9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin
      treated rats, and in 1 of 9 (22.2%) rats comprising the combination group.
      Results of bacterial counts in the bone samples were expressed as log(10) CFU/g
      of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's
      multiple-comparison test. Based on bacterial counts, treatment with daptomycin
      was significantly superior to placebo, although it remained inferior to treatment
      with fosfomycin. No synergistic or antagonistic effect was observed for the
      combination therapy. No development of resistance against daptomycin or
      fosfomycin was observed after the 4-week treatment period.

PMID- 21859943
TI  - Transmission of dapsone-resistant leprosy detected by molecular epidemiological
      approaches.
AB  - Drug resistance surveillance identified six untreated leprosy patients in the
      Philippines with Mycobacterium leprae folP1 mutations which confer dapsone
      resistance. Five patients share a village of residence; four who carried the
      mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat
      (VNTR) strain types. In India, folP1 mutations were detected in two relapse
      patients with a history of dapsone treatment. Mutations were not found in the
      rifampin target gene rpoB. These findings indicate that dapsone resistance is
      being transmitted.

PMID- 21859944
TI  - Prior caspofungin exposure in patients with hematological malignancies is a risk
      factor for subsequent fungemia due to decreased susceptibility in Candida spp.: a
      case-control study in Paris, France.
AB  - Infections due to caspofungin-resistant Candida isolates in patients exposed to
      caspofungin therapy are increasing. We report here a nested case-control study
      which aimed at identifying factors associated with bloodstream infections caused
      by Candida spp. having reduced susceptibility to caspofungin (CRSC) in adults
      suffering from hematological malignancies. In univariate and multivariate
      analyses, infections with CRSC were associated with caspofungin exposure in the
      previous 30 days (odds ratio [OR] = 5.25; 95% confidence interval [95% CI], 1.68
      16.35) and with an age of <= 65 years (OR = 3.27; 95% CI, 1.26-8.50).

PMID- 21859945
TI  - Functional synergy between antimicrobial peptoids and peptides against Gram
      negative bacteria.
AB  - Antimicrobial peptides (AMPs) are integral components of innate immunity and are
      typically found in combinations in which they can synergize for broader-spectrum
      or more potent activity. Previously, we reported peptoid mimics of AMPs with
      potent and selective antimicrobial activity. Using checkerboard assays, we
      demonstrate that peptoids and AMPs can interact synergistically, with fractional
      inhibitory concentration indices as low as 0.16. These results strongly suggest
      that antimicrobial peptoids and peptides are functionally and mechanistically
      analogous.

PMID- 21859946
TI  - Cethromycin-mediated protection against the plague pathogen Yersinia pestis in a
      rat model of infection and comparison with levofloxacin.
AB  - The Gram-negative plague bacterium, Yersinia pestis, has historically been
      regarded as one of the deadliest pathogens known to mankind, having caused three
      major pandemics. After being transmitted by the bite of an infected flea
      arthropod vector, Y. pestis can cause three forms of human plague: bubonic,
      septicemic, and pneumonic, with the latter two having very high mortality rates.
      With increased threats of bioterrorism, it is likely that a multidrug-resistant
      Y. pestis strain would be employed, and, as such, conventional antibiotics
      typically used to treat Y. pestis (e.g., streptomycin, tetracycline, and
      gentamicin) would be ineffective. In this study, cethromycin (a ketolide
      antibiotic which inhibits bacterial protein synthesis and is currently in
      clinical trials for respiratory tract infections) was evaluated for antiplague
      activity in a rat model of pneumonic infection and compared with levofloxacin,
      which operates via inhibition of bacterial topoisomerase and DNA gyrase.
      Following a respiratory challenge of 24 to 30 times the 50% lethal dose of the
      highly virulent Y. pestis CO92 strain, 70 mg of cethromycin per kg of body weight
      (orally administered twice daily 24 h postinfection for a period of 7 days)
      provided complete protection to animals against mortality without any toxic
      effects. Further, no detectable plague bacilli were cultured from infected
      animals' blood and spleens following cethromycin treatment. The antibiotic was
      most effective when administered to rats 24 h postinfection, as the animals
      succumbed to infection if treatment was further delayed. All cethromycin-treated
      survivors tolerated 2 subsequent exposures to even higher lethal Y. pestis doses
      without further antibiotic treatment, which was related, in part, to the
      development of specific antibodies to the capsular and low-calcium-response V
      antigens of Y. pestis. These data demonstrate that cethromycin is a potent
      antiplague drug that can be used to treat pneumonic plague.

PMID- 21859947
TI  - Preliminary testing of an asthma distance education program (ADEP) for school
      nurses in Appalachia.
AB  - Asthma remains one of the most challenging chronic illnesses faced by school
      nurses both nationally and in the State of West Virginia. There is a clear need
      to provide ongoing continuing asthma education to school nurses. However, nurses
      face many barriers to receiving this education. The purpose of this pilot project
      was to develop and evaluate distance learning technology as a method to deliver
      continuing asthma education to school nurses in West Virginia. A sample of 20
      school nurses from 2 counties in West Virginia participated in the study using
      the Wimba live classroom distance learning program. Significant modest
      improvements were found in both the intervention groups compared to a control
      group postintervention. The results of this pilot study are promising and show
      that distance learning technology could be a viable solution for school nurses to
      receive asthma continuing education.

PMID- 21859948
TI  - Uncovering the proteome response of the master circadian clock to light using an
      AutoProteome system.
AB  - In mammals, the suprachiasmatic nucleus (SCN) is the central circadian pacemaker
      that governs rhythmic fluctuations in behavior and physiology in a 24-hr cycle
      and synchronizes them to the external environment by daily resetting in response
      to light. The bilateral SCN is comprised of a mere ~20,000 neurons serving as
      cellular oscillators, a fact that has, until now, hindered the systematic study
      of the SCN on a global proteome level. Here we developed a fully automated and
      integrated proteomics platform, termed AutoProteome system, for an in-depth
      analysis of the light-responsive proteome of the murine SCN. All requisite steps
      for a large-scale proteomic study, including preconcentration, buffer exchanging,
      reduction, alkylation, digestion and online two-dimensional liquid chromatography
      tandem MS analysis, are performed automatically on a standard liquid
      chromatography-MS system. As low as 2 ng of model protein bovine serum albumin
      and up to 20 MUg and 200 MUg of SCN proteins can be readily processed and
      analyzed by this system. From the SCN tissue of a single mouse, we were able to
      confidently identify 2131 proteins, of which 387 were light-regulated based on a
      spectral counts quantification approach. Bioinformatics analysis of the light
      inducible proteins reveals their diverse distribution in different canonical
      pathways and their heavy connection in 19 protein interaction networks. The
      AutoProteome system identified vasopressin-neurophysin 2-copeptin and casein
      kinase 1 delta, both of which had been previously implicated in clock timing
      processes, as light-inducible proteins in the SCN. Ras-specific guanine
      nucleotide-releasing factor 1, ubiquitin protein ligase E3A, and X-linked
      ubiquitin specific protease 9, none of which had previously been implicated in
      SCN clock timing processes, were also identified in this study as light-inducible
      proteins. The AutoProteome system opens a new avenue to systematically explore
      the proteome-wide events that occur in the SCN, either in response to light or
      other stimuli, or as a consequence of its intrinsic pacemaker capacity.

PMID- 21859950
TI  - Effectiveness of three decontamination treatments against influenza virus applied
      to filtering facepiece respirators.
AB  - Filtering facepiece respirators (FFRs) are recommended for use as precautions
      against airborne pathogenic microorganisms; however, during pandemics demand for
      FFRs may far exceed availability. Reuse of FFRs following decontamination has
      been proposed but few reported studies have addressed the feasibility. Concerns
      regarding biocidal efficacy, respirator performance post decontamination,
      decontamination cost, and user safety have impeded adoption of reuse measures.
      This study examined the effectiveness of three energetic decontamination methods
      [ultraviolet germicidal irradiation (UVGI), microwave-generated steam, and moist
      heat] on two National Institute for Occupational Safety and Health-certified N95
      FFRs (3M models 1860s and 1870) contaminated with H5N1. An aerosol settling
      chamber was used to apply virus-laden droplets to FFRs in a method designed to
      simulate respiratory deposition of droplets onto surfaces. When FFRs were
      examined post decontamination by viral culture, all three decontamination methods
      were effective, reducing virus load by > 4 log median tissue culture infective
      dose. Analysis of treated FFRs using a quantitative molecular amplification assay
      (quantitative real-time polymerase chain reaction) indicated that UVGI
      decontamination resulted in lower levels of detectable viral RNA than the other
      two methods. Filter performance was evaluated before and after decontamination
      using a 1% NaCl aerosol. As all FFRs displayed <5% penetration by 300-nm
      particles, no profound reduction in filtration performance was caused in the FFRs
      tested by exposure to virus and subsequent decontamination by the methods used.
      These findings indicate that, when properly implemented, these methods
      effectively decontaminate H5N1 on the two FFR models tested and do not
      drastically affect their filtering function; however, other considerations may
      influence decisions to reuse FFRs.

PMID- 21859949
TI  - Identification of glycan structure alterations on cell membrane proteins in
      desoxyepothilone B resistant leukemia cells.
AB  - Resistance to tubulin-binding agents used in cancer is often multifactorial and
      can include changes in drug accumulation and modified expression of tubulin
      isotypes. Glycans on cell membrane proteins play important roles in many cellular
      processes such as recognition and apoptosis, and this study investigated whether
      changes to the glycan structures on cell membrane proteins occur when cells
      become resistant to drugs. Specifically, we investigated the alteration of glycan
      structures on the cell membrane proteins of human T-cell acute lymphoblastic
      leukemia (CEM) cells that were selected for resistance to desoxyepothilone B
      (CEM/dEpoB). The glycan profile of the cell membrane glycoproteins was obtained
      by sequential release of N- and O-glycans from cell membrane fraction dotted onto
      polyvinylidene difluoride membrane with PNGase F and beta-elimination
      respectively. The released glycan alditols were analyzed by liquid chromatography
      (graphitized carbon)-electrospray ionization tandem MS. The major N-glycan on CEM
      cell was the core fucosylated alpha2-6 monosialo-biantennary structure. Resistant
      CEM/dEpoB cells had a significant decrease of alpha2-6 linked sialic acid on N
      glycans. The lower alpha2-6 sialylation was caused by a decrease in activity of
      beta-galactoside alpha2-6 sialyltransferase (ST6Gal), and decreased expression of
      the mRNA. It is clear that the membrane glycosylation of leukemia cells changes
      during acquired resistance to dEpoB drugs and that this change occurs globally on
      all cell membrane glycoproteins. This is the first identification of a specific
      glycan modification on the surface of drug resistant cells and the mechanism of
      this downstream effect on microtubule targeting drugs may offer a route to new
      interventions to overcome drug resistance.

PMID- 21859951
TI  - Tracking a defined route for O2 migration in a dioxygen-activating diiron enzyme.
AB  - For numerous enzymes reactive toward small gaseous compounds, growing evidence
      indicates that these substrates diffuse into active site pockets through defined
      pathways in the protein matrix. Toluene/o-xylene monooxygenase hydroxylase is a
      dioxygen-activating enzyme. Structural analysis suggests two possible pathways
      for dioxygen access through the alpha-subunit to the diiron center: a channel or
      a series of hydrophobic cavities. To distinguish which is utilized as the O(2)
      migration pathway, the dimensions of the cavities and the channel were
      independently varied by site-directed mutagenesis and confirmed by X-ray
      crystallography. The rate constants for dioxygen access to the diiron center were
      derived from the formation rates of a peroxodiiron(III) intermediate, generated
      upon treatment of the diiron(II) enzyme with O(2). This reaction depends on the
      concentration of dioxygen to the first order. Altering the dimensions of the
      cavities, but not the channel, changed the rate of dioxygen reactivity with the
      enzyme. These results strongly suggest that voids comprising the cavities in
      toluene/o-xylene monooxygenase hydroxylase are not artifacts of protein
      packing/folding, but rather programmed routes for dioxygen migration through the
      protein matrix. Because the cavities are not fully connected into the diiron
      active center in the enzyme resting state, conformational changes will be
      required to facilitate dioxygen access to the diiron center. We propose that such
      temporary opening and closing of the cavities may occur in all bacterial
      multicomponent monooxygenases to control O(2) consumption for efficient
      catalysis. Our findings suggest that other gas-utilizing enzymes may employ
      similar structural features to effect substrate passage through a protein matrix.

PMID- 21859952
TI  - Protons migrate along interfacial water without significant contributions from
      jumps between ionizable groups on the membrane surface.
AB  - Proton diffusion along membrane surfaces is thought to be essential for many
      cellular processes such as energy transduction. Commonly, it is treated as a
      succession of jumps between membrane-anchored proton-binding sites. Our
      experiments provide evidence for an alternative model. We released membrane-bound
      caged protons by UV flashes and monitored their arrival at distant sites by
      fluorescence measurements. The kinetics of the arrival is probed as a function of
      distance for different membranes and for different water isotopes. We found that
      proton diffusion along the membrane is fast even in the absence of ionizable
      groups in the membrane, and it decreases strongly in D(2)O as compared to H(2)O.
      We conclude that the fast proton transport along the membrane is dominated by
      diffusion via interfacial water, and not via ionizable lipid moieties.

PMID- 21859953
TI  - The retrovirus XMRV is not directly involved in the pathogenesis of common types
      of lymphoid malignancy.
AB  - BACKGROUND: A novel retrovirus, xenotropic murine leukemia virus-related virus
      (XMRV), has been detected in prostate cancer samples and in peripheral blood
      mononuclear cells (PBMC) from patients with chronic fatigue syndrome. In
      addition, the virus has been identified in PBMCs from healthy controls. These
      data suggest that XMRV is circulating in the human population. XMRV is closely
      related to murine leukemia viruses, which cause lymphoid malignancies in mice.
      The aim of this study was to determine whether XMRV is directly associated with
      common forms of human lymphoma or leukemia. METHODS: DNA samples from 368
      patients with lymphoid malignancies and 139 patients with benign lymphadenopathy
      or other malignant disease were screened for XMRV, using three specific and
      sensitive quantitative PCR assays. RESULTS: XMRV was not detected in any sample
      using any of the three assays. CONCLUSIONS: The data suggest that this virus is
      not directly involved in the pathogenesis of common types of lymphoid malignancy
      and that XMRV is not a prevalent blood borne infection, at least in the United
      Kingdom. IMPACT: There is no evidence that XMRV is associated with lymphoid
      malignancies, and further studies should resolve inconsistencies in results of
      studies examining XMRV prevalence.

PMID- 21859955
TI  - TLR9 in peritoneal B-1b cells is essential for production of protective self
      reactive IgM to control Th17 cells and severe autoimmunity.
AB  - The role of TLR9 in the development of the autoimmune disease systemic lupus
      erythematosus is controversial. In different mouse models of the disease, loss of
      TLR9 abolishes the generation of anti-nucleosome IgG autoantibodies but at the
      same time exacerbates lupus disease. However, the TLR9-dependent tolerance
      mechanism is unknown. In this study, we show that loss of TLR9 is associated with
      low peritoneal B-1b cell numbers and low levels of protective self-reactive IgM
      serum autoantibodies in lupus-prone FcgammaRIIB-deficient mice leading to the
      uncontrolled accumulation of proinflammatory CD4(+) cells and exacerbated
      autoimmunity. TLR7 signaling was not able to compensate for the loss of TLR9
      signaling in peritoneal B-1b cells to induce IgM Abs. Transfer of TLR9-expressing
      peritoneal B-1b cells from FcgammaRIIB-deficient mice or of recombinant
      monoclonal self-reactive IgM Abs was sufficient to reduce the frequency of
      proinflammatory Th17 cells and lupus disease in FcgammaRIIB/TLR9 double-deficient
      mice. Taken together, these data provide evidence for a TLR9-dependent tolerance
      mechanism of peritoneal B-1b cells generating protective self-reactive IgM in
      lupus-prone mice to control Th17 cell development and severe autoimmunity.

PMID- 21859954
TI  - Analysis of cagA in Helicobacter pylori strains from Colombian populations with
      contrasting gastric cancer risk reveals a biomarker for disease severity.
AB  - BACKGROUND: Helicobacter pylori infection is a risk factor for the development of
      gastric cancer, and the bacterial oncoprotein CagA contributes to gastric
      carcinogenesis. METHODS: We analyzed H. pylori isolates from persons in Colombia
      and observed that there was marked variation among strains in levels of CagA
      expression. To elucidate the basis for this variation, we analyzed sequences
      upstream from the CagA translational initiation site in each strain. RESULTS: A
      DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was
      associated with high levels of CagA expression. Experimental studies showed that
      this motif was necessary but not sufficient for high-level CagA expression. H.
      pylori strains from a region of Colombia with high gastric cancer rates expressed
      higher levels of CagA than did strains from a region with lower gastric cancer
      rates, and Colombian strains of European phylogeographic origin expressed higher
      levels of CagA than did strains of African origin. Histopathologic analysis of
      gastric biopsy specimens revealed that strains expressing high levels of CagA or
      containing the AATAAGATA motif were associated with more advanced precancerous
      lesions than those found in persons infected with strains expressing low levels
      of CagA or lacking the AATAAGATA motif. CONCLUSIONS: CagA expression varies
      greatly among H. pylori strains. The DNA motif identified in this study is
      associated with high levels of CagA expression, and may be a useful biomarker to
      predict gastric cancer risk. IMPACT: These findings help to explain why some
      persons infected with cagA-positive H. pylori develop gastric cancer and others
      do not.

PMID- 21859956
TI  - Stem cell factor consistently improves thymopoiesis after experimental
      transplantation of murine or human hematopoietic stem cells in immunodeficient
      mice.
AB  - Deficient thymopoiesis is a pivotal determinant of impaired immune competence
      following hematopoietic stem cell transplantation (HSCT). Stem cell factor (SCF)
      is essentially involved in early thymopoiesis. We evaluated whether SCF
      administration would improve recovery of thymopoiesis following HSCT in
      immunodeficient mice receiving: 1) bone marrow (BM) transplantation of congenic
      mice; or 2) human fetal liver HSCT in the human immune system mouse model.
      Following murine BM transplantation, SCF significantly enhanced thymopoiesis and
      peripheral T cell recovery in lymph nodes and spleen. SCF did not affect BM
      lymphoid progenitor recovery and/or expansion. Median thymic cellularity
      increased from 0.9 in PBS- to 266 * 10(4)/thymus in SCF-treated mice (p = 0.05).
      Following human HSCT in human immune system mice, higher thymic cellularity was
      observed in SCF-treated mice. Double-negative and early double-positive thymocyte
      subsets increased, but especially late double-positive, CD4 single-positive, and
      CD8 single-positive thymocyte subsets were significantly enhanced (p < 0.05).
      These results show that exogenous supply of SCF may significantly improve murine
      and human posttransplant thymopoiesis, for which the effect is probably exerted
      by directly promoting T cell development intrathymically rather than by enhanced
      entry of prethymically expanded lymphoid progenitors.

PMID- 21859957
TI  - Dual TCR expression biases lung inflammation in DO11.10 transgenic mice and
      promotes neutrophilia via microbiota-induced Th17 differentiation.
AB  - A commonly used mouse model of asthma is based on i.p. sensitization to OVA
      together with aluminum hydroxide (alum). In wild-type BALB/c mice, subsequent
      aerosol challenge using this protein generates an eosinophilic inflammation
      associated with Th2 cytokine expression. By constrast, in DO11.10 mice, which are
      transgenic for an OVA-specific TCR, the same treatment fails to induce
      eosinophilia, but instead promotes lung neutrophilia. In this study, we show that
      this neutrophilic infiltration results from increased IL-17A and IL-17F
      production, whereas the eosinophilic response could be restored upon blockade of
      IFN-gamma, independently of the Th17 response. In addition, we identified a
      CD4(+) cell population specifically present in DO11.10 mice that mediates the
      same inflammatory response upon transfer into RAG2(-/-) mice. This population
      contained a significant proportion of cells expressing an additional endogenous
      TCR alpha-chain and was not present in RAG2(-/-) DO11.10 mice, suggesting dual
      antigenic specificities. This particular cell population expressed markers of
      memory cells, secreted high levels of IL-17A, and other cytokines after short
      term restimulation in vitro, and triggered a neutrophilic response in vivo upon
      OVA aerosol challenge. The relative numbers of these dual TCR lymphocytes
      increased with the age of the animals, and IL-17 production was abolished if mice
      were treated with large-spectrum antibiotics, suggesting that their
      differentiation depends on foreign Ags provided by gut microflora. Taken
      together, our data indicate that dual TCR expression biases the OVA-specific
      response in DO11.10 mice by inhibiting eosinophilic responses via IFN-gamma and
      promoting a neutrophilic inflammation via microbiota-induced Th17
      differentiation.

PMID- 21859959
TI  - Defense-related calcium signaling mutants uncovered via a quantitative high
      throughput screen in Arabidopsis thaliana.
AB  - Calcium acts as a second messenger for signaling to a variety of stimuli
      including MAMPs (Microbe-Associated Molecular Patterns), such as flg22 and elf18
      that are derived from bacterial flagellin and elongation factor Tu, respectively.
      Here, Arabidopsis thaliana mutants with changed calcium elevation (cce) in
      response to flg22 treatment were isolated and characterized. Besides novel mutant
      alleles of the flg22 receptor, FLS2 (Flagellin-Sensitive 2), and the receptor
      associated kinase, BAK1 (Brassinosteroid receptor 1-Associated Kinase 1), the new
      cce mutants can be categorized into two main groups-those with a reduced or an
      enhanced calcium elevation. Moreover, cce mutants from both groups show
      differential phenotypes to different sets of MAMPs. Thus, these mutants will
      facilitate the discovery of novel components in early MAMP signaling and bridge
      the gaps in current knowledge of calcium signaling during plant-microbe
      interactions. Last but not least, the screening method is optimized for speed
      (covering 384 plants in 3 or 10 h) and can be adapted to genetically dissect any
      other stimuli that induce a change in calcium levels.

PMID- 21859958
TI  - Expression of the leptin receptor outside of bone marrow-derived cells regulates
      tuberculosis control and lung macrophage MHC expression.
AB  - Leptin is a pleiotropic hormone proposed to link nutritional status to the
      development of strong Th1 immunity. Because Mycobacterium tuberculosis control is
      affected by starvation and diabetes, we studied the role of the leptin receptor
      in regulating distinct immune cells during chronic infection. Infected db/db
      mice, bearing a natural mutation in the leptin receptor, have a markedly
      increased bacterial load in their lungs when compared with that of their wild
      type counterparts. In response to M. tuberculosis infection, db/db mice exhibited
      disorganized granulomas, neutrophilia, and reduced B cell migration to the lungs,
      correlating with dysfunctional lung chemokine responses that include XCL1, CCL2,
      CXCL1, CXCL2, and CXCL13. In a db/db lung, myeloid cells were delayed in their
      production of inducible NO synthase and had reduced expression of MHC I and II.
      Although the Th1 cell response developed normally in the absence of leptin
      signaling, production of pulmonary IFN-gamma was delayed and ineffective.
      Surprisingly, a proper immune response took place in bone marrow (BM) chimeras
      lacking leptin receptor exclusively in BM-derived cells, indicating that leptin
      acts indirectly on immune cells to modulate the antituberculosis response and
      bacterial control. Together, these findings suggest that the pulmonary response
      to M. tuberculosis is affected by the host's nutritional status via the
      regulation of non-BM-derived cells, not through direct action of leptin on Th1
      immunity.

PMID- 21859960
TI  - A novel rice gene, NRR responds to macronutrient deficiency and regulates root
      growth.
AB  - To better understand the response of rice to nutrient stress, we have taken a
      systematic approach to identify rice genes that respond to deficiency of
      macronutrients and affect rice growth. We report here the expression and
      biological functions of a previously uncharacterized rice gene that we have named
      NRR (nutrition response and root growth). NRR is alternatively spliced, producing
      two 5'-coterminal transcripts, NRRa and NRRb, encoding two proteins of 308 and
      223 aa, respectively. Compared to NRRb, NRRa possesses an additional CCT domain
      at the C-terminus. Expression of NRR in rice seedling roots was significantly
      influenced by deficiency of macronutrients. Knock-down of expression of NRRa or
      NRRb by RNA interference resulted in enhanced rice root growth. By contrast,
      overexpression of NRRa in rice exhibited significantly retarded root growth.
      These results revealed that both NRRa and NRRb played negative regulatory roles
      in rice root growth. Our findings suggest that NRRa and NRRb, acting as the key
      components, modulate the rice root architecture with the availability of
      macronutrients.

PMID- 21859961
TI  - Attenuation of brain damage and cognitive impairment by direct renin inhibition
      in mice with chronic cerebral hypoperfusion.
AB  - The role of the renin-angiotensin system in cognitive impairment is unclear. This
      work was undertaken to test our hypothesis that renin-angiotensin system may
      contribute to cognitive decline and brain damage caused by chronic cerebral
      ischemia. C57BL/6J mice were subjected to bilateral common carotid artery
      stenosis with microcoil to prepare mice with chronic cerebral hypoperfusion, a
      model of subcortical vascular dementia. The effects of aliskiren, a direct renin
      inhibitor, or Tempol, a superoxide scavenger, on brain damage and working memory
      in these mice were examined. Chronic cerebral hypoperfusion significantly
      increased brain renin activity and angiotensinogen expression in C57BL/6J mice,
      which was attributed to the increased renin in activated astrocytes and
      microvessels and the increased angiotensinogen in activated astrocytes in white
      matter. Aliskiren pretreatment significantly inhibited brain renin activity and
      ameliorated brain p67(phox)-related NADPH oxidase activity, oxidative stress,
      glial activation, white matter lesion, and spatial working memory deficits in
      C57BL/6J mice with bilateral common carotid artery stenosis. To elucidate the
      role of oxidative stress in brain protective effects of aliskiren, we also
      examined the effect of Tempol in the same mice with bilateral common carotid
      artery stenosis. Tempol pretreatment mimicked the brain protective effects of
      aliskiren in this mouse model. Posttreatment of mice with aliskiren or Tempol
      after bilateral common carotid artery stenosis also prevented cognitive decline.
      In conclusion, chronic cerebral hypoperfusion induced the activation of the brain
      renin-angiotensin system. Aliskiren ameliorated brain damage and working memory
      deficits in the model of chronic cerebral ischemia through the attenuation of
      oxidative stress. Thus, direct renin inhibition seems to be a promising
      therapeutic strategy for subcortical vascular dementia.

PMID- 21859962
TI  - Superoxide modulates myogenic contractions of mouse afferent arterioles.
AB  - Reactive oxygen species enhance or impair autoregulation. Because superoxide is a
      vasoconstrictor, we tested the hypothesis that stretch generates superoxide that
      mediates myogenic responses. Increasing perfusion pressure of mouse isolated
      perfused renal afferent arterioles from 40 to 80 mm Hg reduced their diameter by
      13.3+/-1.8% (P<0.001) and increased reactive oxygen species (ethidium:
      dihydroethidium fluorescence) by 9.8+/-2.3% (P<0.05). Stretch-induced
      fluorescence was reduced significantly (P<0.05) by incubation with Tempol (3.7+/
      0.8%), pegylated superoxide dismutase (3.2+/-1.0%), or apocynin (3.5+/-0.9%) but
      not by pegylated catalase, L-nitroarginine methylester, or Ca(2+)-free medium,
      relating it to Ca(2+)-independent vascular superoxide. Compared with vehicle,
      basal tone and myogenic contractions were reduced significantly (P<0.05) by
      pegylated superoxide dismutase (5.4+/-0.8), Tempol (4.1+/-1.0%), apocynin (1.0+/
      1.3%), and diphenyleneiodinium (3.9+/-0.9%) but not by pegylated catalase (10.1+/
      1.6%). L-Nitroarginine methylester enhanced basal tone, but neither it (15.8+/
      3.3%) nor endothelial NO synthase knockout (10.2+/-1.8%) significantly changed
      myogenic contractions. Tempol had no further effect after superoxide dismutase
      but remained effective after catalase. H(2)O(2) >50 MUmol/L caused contractions
      but at 25 MUmol/L inhibited myogenic responses (7.4+/-0.8%; P<0.01). In
      conclusion, increasing the pressure within afferent arterioles led to Ca(2+)
      independent increased vascular superoxide production from nicotinamide adenine
      dinucleotide phosphate oxidase, which enhanced myogenic contractions largely
      independent of NO, whereas H(2)O(2) impaired pressure-induced contractions but
      was not implicated in the normal myogenic response.

PMID- 21859963
TI  - Proteinase-activated receptors 1 and 2 exert opposite effects on renal renin
      release.
AB  - Proteinase-activated receptors (PARs) 1 to 4 are highly expressed in the kidney
      and are involved in the regulation of renal hemodynamics and tubular function.
      Since intravascular infusion of the proteinase thrombin, which activates PARs,
      has been shown to decrease plasma renin activity in rats, we investigated the
      effects of the respective PAR subtypes on renin release using the isolated
      perfused mouse kidney model. Thrombin dose-dependently reduced perfusate flow and
      inhibited renin secretion rates (RSRs) that had been prestimulated by the beta
      adrenoreceptor agonist isoproterenol. The suppression of RSRs was prevented by
      the selective PAR1 inhibitor SCH79797, and direct activation of PAR1 by TFLLR
      mimicked the effects of thrombin on RSRs and vascular tone. Moreover, TFLLR
      suppressed the stimulations of RSRs in response to the loop diuretic bumetanide,
      to prostaglandin E(2), or to a decrease in renal perfusion pressure but not in
      response to a reduction in extracellular calcium. The PAR2-activating peptide
      SLIGRL concentration dependently increased RSR and perfusate flow. The
      stimulation of RSRs by SLIGRL was markedly attenuated by N(G)-nitro-L-arginine
      methyl ester, suggesting an NO-dependent mechanism. Activation of PAR4 by AYPGKF
      did not modulate RSRs or perfusate flow. PAR1 and PAR2 immunoreactivity were
      detected in the juxtaglomerular region and were colocalized with renin
      immunoreactivity. Our data provide evidence that PAR1 activation inhibits renal
      renin secretion and induces renal vasoconstriction, whereas PAR2 activation
      stimulates renin release and induces vasodilation mainly via the release of NO.

PMID- 21859964
TI  - Endothelial dysfunction and low-grade inflammation are associated with greater
      arterial stiffness over a 6-year period.
AB  - Endothelial dysfunction and low-grade inflammation are associated with
      cardiovascular disease. Arterial stiffening plays an important role in
      cardiovascular disease and, thus, may be a mechanism through which endothelial
      dysfunction and/or low-grade inflammation lead to cardiovascular disease. We
      investigated the associations between, on the one hand, biomarkers of endothelial
      dysfunction (soluble endothelial selectin, thrombomodulin, and both vascular and
      intercellular adhesion molecules 1 and von Willebrand factor) and of low-grade
      inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8,
      tumor necrosis factor-alpha and, soluble intercellular adhesion molecule 1) and,
      on the other hand, arterial stiffness over a 6-year period, in 293 healthy adults
      (155 women). Biomarkers were combined into mean z scores. Carotid, femoral, and
      brachial arterial stiffness and carotid-femoral pulse wave velocity were
      determined by ultrasonography. Measurements were obtained when individuals were
      36 and 42 years of age. Associations were analyzed with generalized estimating
      equation and adjusted for sex, height, and mean arterial pressure. The
      endothelial dysfunction z score was inversely associated with femoral
      distensibility (beta: -0.51 [95% CI: -0.95 to -0.06]) and compliance coefficients
      (beta: -0.041 [95% CI: -0.076 to -0.006]) but not with carotid or brachial
      stiffness or carotid-femoral pulse wave velocity. The low-grade inflammation z
      score was inversely associated with femoral distensibility (beta: -0.51 [95% CI: 
      0.95 to -0.07]) and compliance coefficients (beta: -0.050 [95% CI: -0.084 to 
      0.016]) and with carotid distensibility coefficient (beta: -0.910 [95% CI: -1.810
      to -0.008]) but not with brachial stiffness or carotid-femoral pulse wave
      velocity. Biomarkers of endothelial dysfunction and low-grade inflammation are
      associated with greater arterial stiffness. This provides evidence that arterial
      stiffening may be a mechanism through which endothelial dysfunction and low-grade
      inflammation lead to cardiovascular disease.

PMID- 21859965
TI  - Key role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in pulmonary vascular
      remodeling and vascular angiogenesis associated with hypoxic pulmonary
      hypertension.
AB  - We have found that 15-hydroxyeicosatetraenoic acid (15-HETE) induced by hypoxia
      was an important mediator in the regulation of hypoxic pulmonary hypertension,
      including the pulmonary vasoconstriction and remodeling. However, the underlying
      mechanisms of the remodeling induced by 15-HETE are poorly understood. In this
      study, we performed immunohistochemistry, pulmonary artery endothelial cells
      migration and tube formation, pulmonary artery smooth muscle cells
      bromodeoxyuridine incorporation, and cell cycle analysis to determine the role of
      15-HETE in hypoxia-induced pulmonary vascular remodeling. We found that hypoxia
      induced pulmonary vascular medial hypertrophy and intimal endothelial cells
      migration and angiogenesis, which were mediated by 15-HETE. Moreover, 15-HETE
      regulated the cell cycle progression and made more smooth muscle cells from the
      G(0)/G(1) phase to the G(2)/M+S phase and enhanced the microtubule formation in
      cell nucleus. In addition, we found that the Rho-kinase pathway was involved in
      15-HETE-induced endothelial cells tube formation and migration and smooth muscle
      cell proliferation. Together, these results show that 15-HETE mediates hypoxia
      induced pulmonary vascular remodeling and stimulates angiogenesis via the Rho
      kinase pathway.

PMID- 21859966
TI  - Renal sympathetic denervation: renal function concerns.

PMID- 21859967
TI  - Historical trends and milestones in hypertension research: a model of the process
      of translational research.

PMID- 21859968
TI  - Role of complement component C1q in the onset of preeclampsia in mice.
AB  - Preeclampsia (PE) is a life-threatening, pregnancy-induced disease and a leading
      cause of maternal and fetal morbidity and mortality. Despite considerable
      research, the causes of PE remain unclear, and there is no effective treatment.
      Studies in animal models that resemble this complex pregnancy-related disorder
      may help to identify possible therapies for PE. Complement component C1q has an
      important role in trophoblast migration, spiral arteries remodeling, and normal
      placentation. Here we show that pregnant C1q-deficient (C1q(-/-)) mice
      recapitulate the key features of human PE: hypertension, albuminuria,
      endotheliosis, decreased placental vascular endothelial growth factor (VEGF) and
      elevated levels of soluble VEGF receptor 1 (sFlt-1) that correlate with increased
      fetal death. In addition, decreased blood flow and increased oxidative stress are
      observed in placentas from C1q(-/-) mice. Treatment of C1q(-/-) mice with
      pravastatin restored trophoblast invasiveness, placental blood flow, and
      angiogenic balance and, thus, prevented the onset of PE. Serum-soluble receptors
      for VEGF-1 levels were reduced and placental VEGF levels were significantly
      increased in C1q(-/-) mice treated with pravastatin compared with untreated C1q(
      /-) mice (VEGF: 1067+/-171 versus 419+/-194 pg/mL; P<0.01). Pravastatin treatment
      reduced hypertension (change in mean arterial pressure: 1+/-1 versus 18+/-3 mm Hg
      in C1q(-/-) untreated mice), and albuminuria (of creatinine) was reduced from
      820+/-175 to 117+/-45 MUg/mg (both P<0.01). Renal damage and endothelial
      dysfunction were significantly attenuated with pravastatin. This model that
      highlights the causative role of impaired trophoblast invasion in the
      pathogenesis of PE allowed us to identify pravastatin as a good therapeutic
      option to prevent PE.

PMID- 21859969
TI  - Pharmacologic suppression of hepatic ATP-binding cassette transporter 1 activity
      in mice reduces high-density lipoprotein cholesterol levels but promotes reverse
      cholesterol transport.
AB  - BACKGROUND: The role of hepatic ATP-binding cassette transporter 1 (ABCA1) in
      maintaining plasma high density lipoprotein cholesterol (HDL-C) levels is well
      established, but its role in reverse cholesterol transport (RCT) is unclear.
      Probucol is a compound that reduces HDL-C levels but also reduces atherosclerosis
      in animal models and xanthomas in humans. The aim of the present study was to
      test the hypothesis that probucol inhibits hepatic ABCA1 activity, thereby
      reducing HDL-C levels but promoting RCT from macrophages. METHODS AND RESULTS:
      Wild-type (WT) C57BL/6 mice and scavenger receptor class B type I (SR-BI)
      knockout mice were fed a chow diet containing 0.5% probucol or normal chow for 2
      weeks. In WT mice, probucol, despite decreasing HDL-C by >80%, effectively
      maintained macrophage RCT. In SR-BI knockout mice, probucol also substantially
      reduced HDL-C but significantly increased macrophage RCT. Furthermore, probucol
      significantly enhanced the excretion of HDL-derived cholesterol into feces in
      both WT and SR-BI knockout mice. Probucol inhibited ABCA1-dependent cholesterol
      efflux from mouse primary hepatocytes, and this effect was shown to be
      responsible for the effect of probucol on increasing the fecal excretion of HDL
      derived cholesterol in vivo. CONCLUSIONS: We demonstrate that pharmacological
      inhibition of hepatic ABCA1 activity with probucol reduced HDL-C levels but
      promoted RCT through diversion of HDL-derived cholesterol from efflux back into
      plasma instead to excretion in the bile. These results explain the beneficial
      effects of probucol on atherosclerosis and xanthomas despite its HDL-lowering
      effects and suggest that inactivation of hepatic ABCA1 leads to increased RCT
      despite reducing plasma HDL-C levels.

PMID- 21859970
TI  - Marine n-3 polyunsaturated fatty acids in adipose tissue and the risk of acute
      coronary syndrome.
AB  - BACKGROUND: Marine n-3 polyunsaturated fatty acids may reduce coronary mortality.
      Previous data in relation to nonfatal coronary disease, however, have been
      inconsistent, which may be explained by the use of heterogeneous methods to
      assess the intake of marine n-3 polyunsaturated fatty acids. We investigated the
      hypothesis that the content of total and individual marine n-3 polyunsaturated
      fatty acids in adipose tissue is negatively associated with the incidence of
      acute coronary syndrome (ACS), including both fatal and nonfatal coronary
      disease. METHODS AND RESULTS: In the Diet, Cancer and Health, a Danish cohort
      study, 57 053 subjects were enrolled and had an adipose tissue biopsy taken at
      inclusion. During a mean follow-up period of 7.6 years, we identified and
      verified all cases (n=1012) with an incident acute coronary syndrome diagnosis,
      and a random sample of the cohort (n=1630) had their fatty acid composition in
      adipose tissue determined by gas chromatography. We found negative dose-response
      associations between the content of total marine n-3 polyunsaturated fatty acids
      and individual n-3 polyunsaturated fatty acids in adipose tissue and the risk of
      acute coronary syndrome. Comparing men in the highest and lowest quintiles gave a
      hazard ratio of 0.65 (95% confidence interval, 0.45 to 0.95) for total n-3
      polyunsaturated fatty acids and 0.51 (95% confidence interval, 0.36 to 0.73) for
      docosahexaenoic acid. Nonfatal cases constituted >86% of cases, and the
      association was driven primarily by a reduction in the risk of nonfatal acute
      coronary syndrome. No consistent associations were found among women. CONCLUSION:
      Intake of marine n-3 polyunsaturated fatty acids may protect against acute
      coronary syndrome in men.

PMID- 21859971
TI  - Improvements in door-to-balloon time in the United States, 2005 to 2010.
AB  - BACKGROUND: Registry studies have suggested improvements in door-to-balloon
      times, but a national assessment of the trends in door-to-balloon times is
      lacking. Moreover, we do not know whether improvements in door-to-balloon times
      were shared equally among patient and hospital groups. METHODS AND RESULTS: This
      analysis includes all patients reported by hospitals to the Centers for Medicare
      & Medicaid Services for inclusion in the time to percutaneous coronary
      intervention (acute myocardial infarction-8) inpatient measure from January 1,
      2005, through September 30, 2010. For each calendar year, we summarized the
      characteristics of patients reported for the measure, including the number and
      percentage in each group, the median time to primary percutaneous coronary
      intervention, and the percentage with time to primary percutaneous coronary
      intervention within 75 minutes and within 90 minutes. Door-to-balloon time
      declined from a median of 96 minutes in the year ending December 31, 2005, to a
      median of 64 minutes in the 3 quarters ending September 30, 2010. There were
      corresponding increases in the percentage of patients who had times <90 minutes
      (44.2% to 91.4%) and <75 minutes (27.3% to 70.4%). The declines in median times
      were greatest among groups that had the highest median times during the first
      period: patients >75 years of age (median decline, 38 minutes), women (35
      minutes), and blacks (42 minutes). CONCLUSION: National progress has been
      achieved in the timeliness of treatment of patients with ST-segment-elevation
      myocardial infarction who undergo primary percutaneous coronary intervention.

PMID- 21859973
TI  - Role of RBM25/LUC7L3 in abnormal cardiac sodium channel splicing regulation in
      human heart failure.
AB  - BACKGROUND: Human heart failure is associated with decreased cardiac voltage
      gated Na+ channel current (encoded by SCN5A), and the changes have been
      implicated in the increased risk of sudden death in heart failure. Nevertheless,
      the mechanism of SCN5A downregulation is unclear. A number of human diseases are
      associated with alternative mRNA splicing, which has received comparatively
      little attention in the study of cardiac disease. Splicing factor expression
      profiles during human heart failure and a specific splicing pathway for SCN5A
      regulation were explored in this study. METHODS AND RESULTS: Gene array
      comparisons between normal human and heart failure tissues demonstrated that 17
      splicing factors, associated with all major spliceosome components, were
      upregulated. Two of these splicing factors, RBM25 and LUC7L3, were elevated in
      human heart failure tissue and mediated truncation of SCN5A mRNA in both Jurkat
      cells and human embryonic stem cell-derived cardiomyocytes. RBM25/LUC7L3-mediated
      abnormal SCN5A mRNA splicing reduced Na+ channel current 91.1+/-9.3% to a range
      known to cause sudden death. Overexpression of either splicing factor resulted in
      an increase in truncated mRNA and a concomitant decrease in the full-length SCN5A
      transcript. CONCLUSIONS: Of the 17 mRNA splicing factors upregulated in heart
      failure, RBM25 and LUC7L3 were sufficient to explain the increase in truncated
      forms and the reduction in full-length Na+ channel transcript. Because the
      reduction in channels was in the range known to be associated with sudden death,
      interruption of this abnormal mRNA processing may reduce arrhythmic risk in heart
      failure.

PMID- 21859974
TI  - Defects in ankyrin-based membrane protein targeting pathways underlie atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia,
      affecting >2 million patients in the United States alone. Despite decades of
      research, surprisingly little is known regarding the molecular pathways
      underlying the pathogenesis of AF. ANK2 encodes ankyrin-B, a multifunctional
      adapter molecule implicated in membrane targeting of ion channels, transporters,
      and signaling molecules in excitable cells. METHODS AND RESULTS: In the present
      study, we report early-onset AF in patients harboring loss-of-function mutations
      in ANK2. In mice, we show that ankyrin-B deficiency results in atrial
      electrophysiological dysfunction and increased susceptibility to AF. Moreover,
      ankyrin-B(+/-) atrial myocytes display shortened action potentials, consistent
      with human AF. Ankyrin-B is expressed in atrial myocytes, and we demonstrate its
      requirement for the membrane targeting and function of a subgroup of voltage
      gated Ca(2+) channels (Ca(v)1.3) responsible for low voltage-activated L-type
      Ca(2+) current. Ankyrin-B is associated directly with Ca(v)1.3, and this
      interaction is regulated by a short, highly conserved motif specific to Ca(v)1.3.
      Moreover, loss of ankyrin-B in atrial myocytes results in decreased Ca(v)1.3
      expression, membrane localization, and function sufficient to produce shortened
      atrial action potentials and arrhythmias. Finally, we demonstrate reduced ankyrin
      B expression in atrial samples of patients with documented AF, further supporting
      an association between ankyrin-B and AF. CONCLUSIONS: These findings support that
      reduced ankyrin-B expression or mutations in ANK2 are associated with AF.
      Additionally, our data demonstrate a novel pathway for ankyrin-B-dependent
      regulation of Ca(v)1.3 channel membrane targeting and regulation in atrial
      myocytes.

PMID- 21859976
TI  - A Patient's Guide to Taking Dabigatran Etexilate.

PMID- 21859972
TI  - Acetylcysteine for prevention of renal outcomes in patients undergoing coronary
      and peripheral vascular angiography: main results from the randomized
      Acetylcysteine for Contrast-induced nephropathy Trial (ACT).
AB  - BACKGROUND: It remains uncertain whether acetylcysteine prevents contrast-induced
      acute kidney injury. METHODS AND RESULTS: We randomly assigned 2308 patients
      undergoing an intravascular angiographic procedure with at least 1 risk factor
      for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes
      mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo.
      The study drugs were administered orally twice daily for 2 doses before and 2
      doses after the procedure. The allocation was concealed (central Web-based
      randomization). All analysis followed the intention-to-treat principle. The
      incidence of contrast-induced acute kidney injury (primary end point) was 12.7%
      in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00;
      95% confidence interval, 0.81 to 1.25; P=0.97). A combined end point of mortality
      or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%,
      respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P=0.92).
      Consistent effects were observed in all subgroups analyzed, including those with
      renal impairment. CONCLUSIONS: In this large randomized trial, we found that
      acetylcysteine does not reduce the risk of contrast-induced acute kidney injury
      or other clinically relevant outcomes in at-risk patients undergoing coronary and
      peripheral vascular angiography. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov. Unique identifier: NCT00736866.

PMID- 21859977
TI  - Images in cardiovascular medicine. Left ventricular outflow tract obstruction
      caused by tamponade.

PMID- 21859979
TI  - Letter by Niccoli et al regarding article, "intracoronary versus intravenous
      administration of abciximab in patients with st-segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention with thrombus
      aspiration: the comparison of intracoronary versus intravenous abciximab
      administration during emergency reperfusion of st-segment elevation myocardial
      infarction (CICERO) trial".

PMID- 21859975
TI  - Association of incident cardiovascular disease with periodic limb movements
      during sleep in older men: outcomes of sleep disorders in older men (MrOS) study.
AB  - BACKGROUND: Periodic limb movements during sleep (PLMS) cause repetitive
      sympathetic activation and may be associated with increased cardiovascular risk.
      We hypothesized that PLMS frequency (periodic limb movement index [PLMI]) and
      PLMS arousal frequency (periodic limb movement arousal index [PLMAI]) are
      predictive of incident cardiovascular disease, including coronary heart disease,
      peripheral arterial disease, and cerebrovascular disease, in an elderly male
      cohort. METHODS AND RESULTS: A total of 2911 men in the observational Outcomes of
      Sleep Disorders in Older Men (MrOS) Sleep Study cohort underwent in-home
      polysomnography with PLMS measurement and were followed up for 4 years for the
      outcomes coronary heart disease, cerebrovascular disease, peripheral arterial
      disease, and all-cause cardiovascular disease, which included coronary heart
      disease, cerebrovascular disease, and peripheral arterial disease. Cox
      proportional hazards regression assessed the association between PLMI, PLMAI, and
      these outcomes. Models were minimally adjusted for age, clinic, and body mass
      index and then fully adjusted for conventional cardiovascular risk factors.
      During follow-up, 500 men experienced all-cause cardiovascular disease: 345
      coronary heart disease, 117 cerebrovascular disease, and 98 peripheral arterial
      disease events. In fully adjusted models, men with PLMAI >=5 compared with the
      referent PLMA <1 group had a 1.26-fold increased relative hazard for all-cause
      cardiovascular disease. Similar findings were observed for PLMI and all-cause
      cardiovascular disease. For peripheral arterial disease, men with PLMI >=30
      compared with the referent PLMI <5 group had a 2-fold increased relative hazard
      (95% confidence interval, 1.14 to 3.49; P=0.025). Compared with the referent
      group, men with PLMI >=30 had an increased risk of coronary heart disease
      (relative hazard, 1.31; 95% confidence interval, 1.01 to 1.70; P=0.045) after
      minimal adjustment, but this association was attenuated after further
      adjustments. After stratification, risk of incident all-cause cardiovascular
      disease among high-PLMI and high-PLMAI groups was significantly elevated only for
      men without prevalent hypertension (P for interactions <0.10). CONCLUSION: These
      findings provide evidence that PLMS frequency is associated with incident
      cardiovascular disease in community-dwelling elderly men.

PMID- 21859980
TI  - Is diabetes the achilles' heel of limus-eluting stents?

PMID- 21859981
TI  - Connexin 37 counteracts clotting.

PMID- 21859982
TI  - Paradigm shift to functional angioplasty: new insights for fractional flow
      reserve- and intravascular ultrasound-guided percutaneous coronary intervention.

PMID- 21859983
TI  - Knowledge, perception, and behaviors of relatives of people with premature heart
      disease: a systematic literature review.

PMID- 21859984
TI  - Images in cardiovascular medicine. Use of embolic protection to prevent stroke
      during catheter ablation of atrial fibrillation.

PMID- 21859985
TI  - Structural resolution of the complex between a fungal polygalacturonase and a
      plant polygalacturonase-inhibiting protein by small-angle X-ray scattering.
AB  - We report here the low-resolution structure of the complex formed by the endo
      polygalacturonase from Fusarium phyllophilum and one of the polygalacturonase
      inhibiting protein from Phaseolus vulgaris after chemical cross-linking as
      determined by small-angle x-ray scattering analysis. The inhibitor engages its
      concave surface of the leucine-rich repeat domain with the enzyme. Both sides of
      the enzyme active site cleft interact with the inhibitor, accounting for the
      competitive mechanism of inhibition observed. The structure is in agreement with
      previous site-directed mutagenesis data and has been further validated with
      structure-guided mutations and subsequent assay of the inhibitory activity. The
      structure of the complex may help the design of inhibitors with improved or new
      recognition capabilities to be used for crop protection.

PMID- 21859986
TI  - Re: Human papillomavirus testing in the prevention of cervical cancer.

PMID- 21859987
TI  - Adjuvant endocrine therapy for breast cancer: don't ditch the switch!

PMID- 21859989
TI  - Androgen receptor rediscovered: the new biology and targeting the androgen
      receptor therapeutically.
AB  - Discoveries over the past decade suggest that castration-resistant prostate
      cancer (CRPC) is sensitive, but not resistant to, further manipulation of the
      androgen-androgen receptor (AR) axis. Several new therapies that target this axis
      have demonstrated clinical activity. In this article, preclinical and clinical
      findings occurring in the field of AR-targeted therapies are reviewed. Reviews of
      scientific and clinical development are divided into those occurring prereceptor
      (androgen production and conversion) and at the level of the receptor (AR
      aberrations and therapies targeting AR directly). Intracrine androgen production
      and AR amplification, among others, are among the principal aberrancies driving
      CRPC growth. Phase III data with abiraterone acetate and phase II data with MDV
      3100, along with other similar therapies, confirm for the clinician that the
      scientific findings related to persistent AR signaling in a castrate milieu can
      be harnessed to produce significant clinical benefit for patients with the
      disease. Studies aimed at optimizing the timing of their use and exploring the
      mechanisms of resistance to these therapies are under way. The clinical success
      of therapies that directly target androgen synthesis as well as the most common
      aberrancies of the AR confirm that prostate cancer retains dependence on AR
      signaling, even in the castrate state.

PMID- 21859988
TI  - End points and outcomes in castration-resistant prostate cancer: from clinical
      trials to clinical practice.
AB  - New therapeutic approaches for castration-resistant prostate cancer (CRPC)
      introduce new treatment dilemmas: how best to sequence these options to maximally
      benefit patients, what tests to perform before and after treatment to assess
      disease status, and how to interpret the test results and use them to guide
      treatment. New and specific end points for different classes of drugs are needed
      to provide the information to guide these treatment decisions. In 2008, the
      Prostate Cancer Working Group 2 consensus criteria for early-phase clinical
      trials redefined clinical trial end points as first, to control, relieve, or
      eliminate disease manifestations present when treatment is started and second, to
      prevent or delay future disease manifestations. Disease manifestations include
      prostate-specific antigen (PSA), soft-tissue disease (nodes and/or viscera), bone
      disease (most common site of spread), and symptoms. Recent US Food and Drug
      Administration (FDA) approvals for CRPC therapies have been based on the
      prevent/delay end points that reflect unequivocal benefit to a patient:
      prolongation of life or reduction in skeletal-related events (SREs). For the
      practicing oncologist, the control/relieve/eliminate outcomes should serve
      primarily to inform the decision of whether to continue therapy. In this review,
      we consider individual end points such as PSA, imaging, and patient-reported
      outcomes in the context of the control/relieve/eliminate and prevent/delay
      framework. We address the time-to-event end points of metastasis prevention, SRE,
      time to progression, and overall survival in the context of regulatory approvals.
      We also discuss circulating tumor cells measured with the CellSearch assay,
      recently cleared by the FDA for monitoring CRPC.

PMID- 21859990
TI  - The black dress.

PMID- 21859991
TI  - Randomized phase II placebo-controlled trial of maintenance therapy using the
      oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed
      ovarian cancer.
AB  - PURPOSE: Inhibiting angiogenesis is one of the most promising avenues for new
      therapies for ovarian cancer. We investigated the efficacy and safety of a novel
      agent, BIBF 1120, a triple angiokinase inhibitor, after chemotherapy for relapsed
      disease. PATIENTS AND METHODS: We conducted a randomized, double-blind,
      controlled phase II trial in 83 patients who had just completed chemotherapy for
      relapsed ovarian cancer, with evidence of response, but at high risk of further
      early recurrence. The patients were randomly assigned to receive maintenance
      therapy using BIBF 1120 250 mg or placebo, twice per day, continuously for 36
      weeks. End points were progression-free survival (PFS), toxicity, and overall
      survival. RESULTS: Thirty-six-week PFS rates were 16.3% and 5.0% in the BIBF 1120
      and placebo groups, respectively (hazard ratio, 0.65; 95% CI, 0.42 to 1.02; P =
      .06). Four patients continued on BIBF 1120, including two patients for another
      year or more. The proportion of patients with any grade 3 or 4 adverse events was
      similar between the groups (34.9% for BIBF 1120 v 27.5% for placebo; P = .49;
      mostly grade 3). However, more patients on BIBF 1120 experienced diarrhea,
      nausea, or vomiting (mainly grade 1 or 2 and no grade 4). There was a higher rate
      of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 (51.2%) compared with
      patients on placebo (7.5%; P < .001), but this was rarely of clinical
      significance, and patients continued with the trial treatment. A single-level
      dose reduction to 150 mg was made in 15 patients, all on active drug. CONCLUSION:
      BIBF 1120 is well tolerated and associated with a potential improvement in PFS.
      The observed treatment effect is sufficient to justify further study within a
      large phase III trial.

PMID- 21859992
TI  - Elevated bone turnover predicts for bone metastasis in postmenopausal breast
      cancer: results of NCIC CTG MA.14.
AB  - PURPOSE: We investigated the association of bone-only relapse with a pretreatment
      marker of bone resorption: serum beta C-terminal telopeptide (B-CTx) of type I
      collagen. METHODS: Pretreatment serum B-CTx concentrations were determined from
      621 of 667 patients with primary breast cancer enrolled onto the NCIC CTG MA.14
      phase III adjuvant trial of tamoxifen with or without octreotide. Recurrence-free
      survival (RFS) was a secondary end point; the focus here was bone-only relapse.
      We analyzed continuous or categorical (.71 ng/mL cut point) serum B-CTx in
      stepwise forward multivariate Cox regression, adjusted for trial stratification
      factors. We also examined B-CTx and bone relapse by pretrial chemotherapy status.
      RESULTS: At median 7.9 years follow-up, 123 of 621 patients experienced
      recurrence; 19 (3.1%) of 621 had bone-only recurrence, and 47 (7.5%) of 621 had
      bone plus other sites of recurrence. Larger pathologic tumor size (P = .001) and
      elevated continuous and categorical serum B-CTx were associated with shorter bone
      only RFS (both P = .02) when added to a model with factors significant in the
      main trial analyses (hazard ratio [HR], 3.43 and 3.50, respectively; 95% CI, 1.20
      to 9.77 and 1.26 to 9.75, respectively). The univariate HR for B-CTx was 2.80
      (95% CI, 1.05 to 7.48; P = .03). Elevated serum B-CTx was also associated with
      shorter bone-only RFS (P = .02) when added to a model with factors significant in
      the main trial analyses. Serum B-CTx level was not associated with any other type
      of recurrence. Serum B-CTx was not significantly different for patients who
      underwent pretrial chemotherapy, compared with those who did not (P = .27), nor
      did pretrial chemotherapy affect bone relapse (P = .48 for bone only; P = .76 for
      bone with other relapse). CONCLUSION: Higher pretreatment serum B-CTx was a
      significant predictor of shorter RFS for bone-only metastasis. Increased bone
      resorption creates an environment that promotes growth of breast cancer cells.

PMID- 21859994
TI  - Can we predict who's at risk for developing bone metastases in breast cancer?

PMID- 21859993
TI  - Common gene rearrangements in prostate cancer.
AB  - Prostate cancer is a common heterogeneous disease, and most patients diagnosed in
      the post prostate-specific antigen (PSA) era present with clinically localized
      disease, the majority of which do well regardless of treatment regimen
      undertaken. Overall, those with advanced prostate cancer at time of diagnosis do
      poorly after androgen withdrawal therapy. Understanding the biologic underpinning
      of prostate cancer is necessary to best determine the risk of disease progression
      and would be advantageous for the development of novel therapeutic approaches to
      impede or prevent disease. This review focuses on the recently identified common
      ETS and non-ETS gene rearrangements in prostate cancer. Although multiple
      molecular alterations have been detected in prostate cancer, a detailed
      understanding of gene fusion prostate cancer should help explain the clinical and
      biologic diversity, providing a rationale for a molecular subclassification of
      the disease.

PMID- 21859995
TI  - Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07
      trial, including survival and subset analyses.
AB  - PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07
      trial demonstrated that the addition of oxaliplatin to fluorouracil plus
      leucovorin (FULV) improved disease-free survival (DFS) in patients with stage II
      or III colon cancer. This analysis is the first publication of overall survival
      (OS) for the NSABP C-07 study. We updated DFS and examined both end points in
      clinically relevant patient subsets. PATIENTS AND METHODS: Other studies have
      identified patients age 70 or older and those with stage II disease as patient
      subsets in which oxaliplatin may not be effective. We investigated toxicity as a
      driver of divergent outcomes in these subsets. RESULTS: In all, 2,409 eligible
      patients with follow-up were randomly assigned to either FULV (FU 500 mg/m(2) by
      intravenous [IV] bolus weekly for 6 weeks; leucovorin 500 mg/m(2) IV weekly for 6
      weeks of each 8-week cycle for three cycles) or FLOX (FULV plus oxaliplatin 85
      mg/m(2) IV on days 1, 15, and 29 of each cycle). With 8 years median follow-up,
      OS was similar between treatment groups (hazard ratio [HR], 0.88; 95% CI, 0.75 to
      1.02; P = .08). FLOX remained superior for DFS (HR, 0.82; 95% CI, 0.72 to 0.93; P
      = .002). The effect of oxaliplatin on OS did not differ by stage of disease
      (interaction P = .38 for OS; interaction P = 0.37 for DFS) but did vary by age
      for OS (younger than age 70 v 70+ interaction P = .039). There was a similar
      trend for DFS (interaction P = .073). Oxaliplatin significantly improved OS in
      patients younger than age 70 (HR, 0.80; 95% CI, 0.68 to 0.95; P = .013), but no
      positive effect was evident in older patients. CONCLUSION: Overall, the addition
      of oxaliplatin to FULV has not been proven to extend OS in this trial, but the
      DFS effect remained strong. Unplanned subset analyses suggest a significant OS
      effect of oxaliplatin in patients younger than age 70.

PMID- 21859996
TI  - Prostate cancer: evolution or revolution?

PMID- 21859997
TI  - Lifetime risk and sex difference of hepatocellular carcinoma among patients with
      chronic hepatitis B and C.
AB  - PURPOSE: Both hepatitis B (HBV) and C viruses (HCV) are causes of hepatocellular
      carcinoma (HCC), but lifetime risk and sex difference remain unclear. This study
      aimed to assess the lifetime risk and sex difference of HCC among patients with
      chronic HBV and/or HCV. METHODS: A prospective cohort of 23,820 residents of
      Taiwan age 30 to 65 years were enrolled from 1991 to 1992, with 477 instances of
      HCC occurring subsequently. Serum samples collected at enrollment were tested for
      seromarkers and viral load of HBV and HCV. Newly developed HCC was ascertained
      through computerized data linkage with national cancer registry and death
      certification systems. RESULTS: The cumulative lifetime (age 30 to 75 years)
      incidences of HCC for men and women positive for both HBV surface antigen (HBsAg)
      and antibodies against HCV (anti-HCV) were 38.35% and 27.40%; for those positive
      for HBsAg only, 27.38% and 7.99%; for those positive for anti-HCV only, 23.73%
      and 16.71%; and for those positive for neither, 1.55% and 1.03%, respectively.
      There was a significant male predominance in incidence of HCC for chronic HBV
      carriers but not for chronic carriers of HCV or both. Multivariate adjusted
      hazard ratio of developing HCC decreased with age in HBsAg-seropositive men but
      increased with age in anti-HCV-seropositive women. Among dual-infected
      participants, there was an inverse association between HBV and HCV viral load.
      Risk of HCC increased significantly with increasing viral load of HBV and HCV.
      CONCLUSION: There exists a suppressive effect of HCV on HBV viral load.
      Individual and combined effects of the two viruses on HCC vary with sex and age.

PMID- 21859998
TI  - Analysis of prognostic factors of comprehensive geriatric assessment and
      development of a clinical scoring system in elderly Asian patients with cancer.
AB  - PURPOSE: To determine the impact of each comprehensive geriatric assessment (CGA)
      domain on overall survival (OS) and develop a prognostic scoring system for
      elderly patients with cancer. PATIENTS AND METHODS: A retrospective analysis of
      CGA data collected from 249 consecutive patients with cancer who attended the
      outpatient geriatric oncology clinic at the National Cancer Center Singapore age
      70 years or older was performed. Univariate and multivariate analyses were
      performed using Cox proportional hazards method to identify significant
      prognostic factors within the CGA. A simple nomogram to predict OS was developed
      using regression coefficients from the multivariate model. Concordance between
      predicted and observed response of the individual patient score was evaluated by
      means of Harrell's c-index. Calibration was performed using simulated data via
      bootstrap. RESULTS: Median age of the patients was 77 years (range, 70 to 94
      years). In our model, age (hazard ratio [HR], 1.04; 95% CI, 1.01 to 1.07),
      abnormal albumin level (HR, 1.97; 95% CI, 1.23 to 3.15), poor Eastern Cooperative
      Oncology Group performance status (>= 2 v < 2: HR, 1.77; 95% CI, 1.15 to 2.72),
      abnormal geriatric depression scale status (HR, 1.81; 95% CI, 1.29 to 2.56), high
      malnutrition risk (high v low risk: HR, 1.84; 95% CI, 1.17 to 2.87), and advanced
      disease stage (late v early: HR, 1.71; 95% CI, 0.98 to 2.95) were independent
      predictors of survival. CONCLUSION: Results confirm the importance of the CGA in
      assessment of elderly patients with cancer. The development of this nomogram
      incorporating these prognostic factors helps predict OS of patients, for further
      intervention.

PMID- 21859999
TI  - The study of collaborative practice arrangements: where do we go from here?

PMID- 21860000
TI  - Randomized phase III trial of sequential adjuvant chemoradiotherapy with or
      without erythropoietin Alfa in patients with high-risk cervical cancer: results
      of the NOGGO-AGO intergroup study.
AB  - PURPOSE: This open-label, randomized phase III study was designed to investigate
      the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and
      pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had
      undergone radical hysterectomy. PATIENTS AND METHODS: Two hundred fifty-seven
      patients were randomly assigned to four cycles of carboplatin/ifosfamide
      chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four
      cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic
      radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free
      survival (RFS). Secondary end points included overall survival (OS), change in
      hemoglobin levels, and safety, including thromboembolic events. RESULTS: The
      estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for
      patients receiving CRT. There was no statistically significant difference in RFS,
      although a trend favoring patients treated with CRT + EPO was observed (hazard
      ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses
      suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR,
      0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR,
      0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88;
      95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained
      higher hemoglobin levels throughout CRT. No significant differences in safety
      profiles were observed between the two groups. Incidence of thrombovascular
      events was low (2%) and comparable between both groups. CONCLUSION: This study
      confirms that EPO can be added safely to CRT in patients with cervical cancer,
      but it failed to demonstrate a significant benefit in RFS and OS.

PMID- 21860002
TI  - Prediction of response to targeted therapies in lung cancer using dynamic
      imaging: still far from clinical implementation.

PMID- 21860003
TI  - Education research: evaluating the use of podcasting for residents during EEG
      instruction: a pilot study.
AB  - OBJECTIVE: Educational methods for residents are shifting toward greater learner
      independence aided by technological advances. A Web-based program using a podcast
      was created for resident EEG instruction, replacing conventional didactics. The
      EEG curriculum also consisted of EEG interpretations under the tutelage of a
      neurophysiologist. This pilot study aimed to objectively evaluate the
      effectiveness of the podcast as a new teaching tool. METHODS: A podcast for
      resident EEG instruction was implemented on the Web, replacing the traditional
      lecture. After Institutional Review Board approval, consent was obtained from the
      participating residents. Using 25-question evaluation tools, participants were
      assessed at baseline before any EEG instruction, and reassessed after podcasting
      and after 10 clinical EEG exposures. Each 25-item evaluation tool contained
      tracings used for clinical EEG interpretations. Scores after podcast training
      were also compared to scores after traditional didactic training from a previous
      study among anesthesiology trainees. RESULTS: Ten anesthesiology residents
      completed the study. The mean scores with standard deviations are 9.50 +/- 2.92
      at baseline, 13.40 +/- 3.31 (p = 0.034) after the podcast, and 16.20 +/- 1.87 (p
      = 0.019) after interpreting 10 EEGs. No differences were noted between the mean
      educational tool scores for those who underwent podcasting training compared to
      those who had undergone traditional didactic training. CONCLUSION: In this pilot
      study, podcast training was as effective as the prior conventional lecture in
      meeting the curricular goals of increasing EEG knowledge after 10 EEG
      interpretations as measured by assessment tools.

PMID- 21860001
TI  - Emerging therapies to prevent skeletal morbidity in men with prostate cancer.
AB  - Skeletal morbidity is a prominent burden to men with advanced prostate cancer
      throughout the natural history of the disease. Bone metastases can cause pain and
      greatly elevate the risk for fractures and other structural complications.
      Distinct from the problem of metastases, treatment-related osteoporosis and
      associated fragility fractures are potential complications of androgen
      deprivation therapy. Bone-targeted therapies for prostate cancer have therefore
      been the focus of considerable research and drug development efforts. The
      osteoclast is a validated therapeutic target in the management of prostate
      cancer. Osteoclast inhibition with zoledronic acid (a bisphosphonate) or with
      denosumab (a monoclonal antibody to RANK ligand) reduces risk for skeletal events
      in men with castration-resistant prostate cancer metastatic to bone. Osteoclast
      inhibition with any of several bisphosphonates improves bone mineral density, a
      surrogate for osteoporotic fracture risk. Denosumab and toremifene (a selective
      estrogen receptor modulator) have each been shown to reduce osteoporotic fracture
      risk among men receiving androgen-deprivation therapy. Beta-emitting
      radiopharmaceuticals reduce pain due to metastatic disease. Investigations
      involving alpha-emitting radium-223, endothelin-A receptor antagonists atrasentan
      and zibotentan, proto-oncogene tyrosine-protein kinase (SRC) inhibitor dasatinib,
      and tyrosine kinase inhibitor cabozantinib (XL184) are ongoing in clinical trials
      and are also discussed.

PMID- 21860004
TI  - Teaching neuroimages: onion-skin pattern facial sensory loss.

PMID- 21860005
TI  - Teaching neuroimages: brain MRI and FDG-PET in malformations of cortical
      development and hippocampal hypoplasia.

PMID- 21860006
TI  - Teaching video neuroimages: Horner syndrome with Dejerine-Klumpke plexopathy.

PMID- 21860009
TI  - Headache attributed to autonomic dysreflexia: an underrecognized clinical entity.
AB  - OBJECTIVE: The recognition and the management of headache attributed to autonomic
      dysreflexia after spinal cord injury (SCI) are challenging issues. Given this, I
      systematically reviewed the literature to establish the features of the headache
      attributed to autonomic dysreflexia after SCI. METHODS: This review included all
      articles that addressed any feature of headache attributed to autonomic
      dysreflexia after SCI. The literature search addressed publications from 1950
      until April 2010. The literature search was conducted using MEDLINE, CINAHL,
      EMBASE, and PsycINFO(r) databases. The literature search was limited to only
      articles written in English. RESULTS: Of the 273 publications captured in all 4
      databases, 45 articles fulfilled our inclusion and exclusion criteria. Typically,
      the headache attributed to autonomic dysreflexia is a sudden-onset, severe
      headache accompanied by several signs and symptoms including increased blood
      pressure, altered heart rate, and diaphoresis cranial to the level of SCI, which
      is triggered by different noxious and nonnoxious stimuli. However, clinicians
      need to be aware of other headache features and the variety of potential triggers
      associated with the headache attributed to autonomic dysreflexia. CONCLUSIONS:
      The greater awareness of this clinical entity among clinicians, in particular
      neurologists, is crucial for early recognition and proper management of episodes
      of autonomic dysreflexia to prevent its complications.

PMID- 21860010
TI  - Necrotizing granulomatous meningoencephalitis due to Balamuthia in an
      immunocompetent child.

PMID- 21860011
TI  - The paradoxical effect of bevacizumab in the therapy of malignant gliomas.

PMID- 21860012
TI  - Progression of carotid intima-media thickness in a contemporary human
      immunodeficiency virus cohort.
AB  - BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at risk
      for premature cardiovascular disease (CVD). Predictors of atherosclerotic disease
      progression in contemporary patients have not been well described. METHODS: Using
      data from a prospective observational cohort of adults infected with HIV (Study
      to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy),
      we assessed common carotid artery intima-media thickness (CIMT) at baseline and
      year 2 by ultrasound. We examined HIV-associated predictors of CIMT progression
      after adjusting for age, sex, race/ethnicity, body mass index, smoking,
      hypertension, diabetes, low-density lipoprotein cholesterol level, and baseline
      CIMT using linear regression. RESULTS: Among 389 participants (median age at
      baseline, 42 years; male sex, 77%; median CD4+ cell count at baseline, 485
      cells/mm3; 78% receiving antiretroviral therapy), the median 2-year CIMT change
      was 0.016 mm (interquartile range, -0.003 to 0.033 mm; P < .001). Lesser CIMT
      progression was associated with a suppressed viral load at baseline (-0.009 mm
      change; P = .015) and remaining virologically suppressed throughout follow-up (
      0.011 mm change; P < .001). After adjusting for additional risk factors and a
      suppressed viral load during follow-up, nonnucleoside reverse transcriptase
      inhibitor versus protease inhibitor exposure was associated with lesser CIMT
      progression (-0.011 mm change; P = .02). CONCLUSIONS: Suppressing HIV replication
      below clinical thresholds was associated with less progression of
      atherosclerosis. The proatherogenic mechanisms of HIV replication and the net CVD
      benefit of different antiretroviral drugs should be a focus of future research.

PMID- 21860013
TI  - Genotypic distribution of hepatitis B virus (HBV) among acute cases of HBV
      infection, selected United States counties, 1999-2005.
AB  - BACKGROUND: Knowledge of the genotypic distribution of hepatitis B virus (HBV)
      facilitates epidemiologic tracking and surveillance of HBV infection as well as
      prediction of its disease burden. In the United States, HBV genotyping studies
      have been conducted for chronic but not acute hepatitis B. METHODS: Serum samples
      were collected from patients with acute hepatitis B cases reported from the 6
      counties that participated in the Sentinel Counties Study of Acute Viral
      Hepatitis from 1999 through 2005. Polymerase chain reaction followed by
      nucleotide sequencing of a 435-base pair segment of the HBV S gene was performed,
      and the sequences were phylogenetically analyzed. RESULTS: Of 614 patients
      identified with available serum samples, 75% were infected with genotype A HBV
      and 18% were infected with genotype D HBV. Thirty-two percent of genotype A
      sequences constituted a single subgenotype A2 cluster. The odds of infection with
      genotype A (vs with genotype D) were 5 times greater among black individuals than
      among Hispanic individuals (odds ratio [OR], 5; 95% confidence interval [CI], 2.3
      10.7). The odds of infection with genotype A were 49, 8, and 4 times greater
      among patients from Jefferson County (Alabama), Pinellas County (Florida), and
      San Francisco (California), respectively, than among those living in Denver
      County (Colorado). Genotype A was less common among recent injection drug users
      than it was among non-injection drug users (OR, 0.2; 95% CI, 0.1-0.4).
      CONCLUSIONS: HBV genotype distribution was significantly associated with
      ethnicity, place of residence, and risk behavior.

PMID- 21860014
TI  - Telomere dynamics in rhesus monkeys: no apparent effect of caloric restriction.
AB  - The role of telomere attrition in limiting the replicative capacity of cells in
      culture is well established. In humans, epidemiologic evidence suggests telomere
      length (TL) in leukocytes is highly variable at birth and inversely related to
      age. Although calorie restriction (CR) significantly increases life span in most
      rodent models, its association with TL is unknown. Using linear regression
      analysis, TLs (as measured by Southern blot analysis) of skeletal muscle (a
      postmitotic tissue that largely represents early development TL), fat,
      leukocytes, and skin were tested for effects of age, sex, and diet in 48 control
      and 23 calorie restriction rhesus monkeys. After controlling for the individual's
      muscle mean TL, differences between leukocytes muscle and skin muscle were
      significantly associated with age (p = .002; p = .002) and sex (p = .003; p =
      .042), but not calorie restriction (p = .884; p = .766). Despite an age-dependent
      shortening of TL in leukocytes and skin, calorie restriction did not
      significantly affect TL dynamics in these samples.

PMID- 21860015
TI  - Long-term cognitive impairment in older adult twins discordant for gynecologic
      cancer treatment.
AB  - BACKGROUND: Research has found that patients treated for cancer generally have an
      increased risk for cognitive problems. However, many studies have focused on
      cognitive performance of cancer patients under the age of 65 who received
      chemotherapy treatment. Less studied is the extent to which cancer diagnosis may
      be associated with cognitive impairment as a late effect for older adults.
      METHODS: In this retrospective, co-twin design study, twin pairs 65 years of age
      and older discordant for cancer were identified from the Swedish Twin Registry. A
      pair was included if both twins participated in cognitive screening, and the twin
      with the cancer history was screened at least 3 years after cancer diagnosis and
      treatment. RESULTS: Female, but not male, survivors of cancer were significantly
      (odds ratio = 2.42, 95% confidence interval = 1.23-4.74) more likely to exhibit
      cognitive impairment 3 or more years after cancer diagnosis and treatment as
      their co-twin without a history of cancer. In particular, risk was higher among
      survivors of gynecologic cancers (odds ratio = 10.00, 95% confidence interval =
      1.28-78.11) and those who had treatments directly or potentially affecting
      ovarian functioning (odds ratio = 13.00, 95% confidence interval = 1.70-99.36)
      compared with their respective co-twins. CONCLUSIONS: These findings suggest that
      localized treatments and other cancer-related factors should be explored as
      determinants that underlie the association between cancer diagnosis and long-term
      cognitive impairment.

PMID- 21860016
TI  - Body mass index, waist circumference, and waist-to-hip ratio as predictors of
      mortality in nonagenarians: the Vitality 90+ Study.
AB  - BACKGROUND: The associations of body mass index (BMI) and abdominal obesity with
      mortality among very old people are poorly known. The purpose of this study was
      to investigate the association of BMI, waist circumference (WC), and waist-to-hip
      ratio with mortality in nonagenarians. METHODS: This study is part of a
      prospective population-based study, Vitality 90+, including both community
      dwelling and institutionalized persons from Tampere, Finland. Altogether 192
      women and 65 men aged 90 years were subjected to anthropometric measurements, a
      baseline interview, and a 4-year mortality follow-up. Cox proportional hazards
      models were used in the statistical analyses. RESULTS: In men, normal weight
      indicated a three times higher mortality risk (hazard ratio [HR] 3.09, 95%
      confidence interval [CI] 1.35-7.06) compared with overweight, and WC was
      inversely associated with mortality (HR 0.96, 95% CI 0.93-1.00) after adjustment
      for covariates. In women, the univariate waist-to-hip ratio (HR 1.43, 95% CI 1.06
      1.92) and BMI-adjusted waist-to-hip ratio (HR 1.45, 95% CI 1.07-1.97) were
      positively associated with mortality. Also, overweight women whose WC was <86 cm
      had lower mortality than normal weight women with similar WC (HR 0.34, 95% CI
      0.12-0.97). CONCLUSIONS: In nonagenarian men, low BMI and low WC predict
      increased mortality. In nonagenarian women, waist-to-hip ratio alone and adjusted
      for BMI is positively associated with mortality. The potential positive effects
      of overweight combined with WC warrant more detailed analyses in larger data. In
      all, future studies are needed to better understand the health and functional
      consequences of body composition among the oldest old.

PMID- 21860018
TI  - Gender and life course occupational social class differences in trajectories of
      functional limitations in midlife: findings from the 1946 British birth cohort.
AB  - BACKGROUND: Older women and those of lower socioeconomic position (SEP)
      consistently constitute a larger portion of the disabled population than older
      men or those of higher SEP, yet no studies have examined when in the life course
      these differences emerge. METHODS: Prevalence of self-reported limitations in the
      upper body (gripping or reaching) and lower body (walking or stair climbing) at
      43 and 53 years were utilized from 1,530 men and 1,518 women from the British
      1946 birth cohort. Generalized linear models with a binomial distribution were
      used to examine the effects of gender, childhood and adult SEP, and the
      differences in the SEP effects by gender on the prevalence of limitations at age
      43 years and changes in prevalence from 43 to 53 years. RESULTS: For both
      genders, the prevalence of upper and lower body limitations were reported at 3%
      5% at age 43 years. However, by age 53 years, women's upper body limitations had
      increased to 28% and lower body limitations to 21%, whereas men's limitations had
      only increased to 12% and 11%, respectively. Men and women whose father's
      occupation was manual or whose adult head of household occupation was manual had
      higher prevalence of both limitations compared with those with non-manual
      backgrounds. These differences widened with age, especially in women. The effect
      of adult SEP on the prevalence of limitations was stronger than that of childhood
      SEP and was partly mediated by educational attainment. CONCLUSION: Our findings
      provide the first evidence that prevention of disability in old age should begin
      early in midlife, especially for women from manual occupation households.

PMID- 21860017
TI  - Age-associated alteration in innate immune response in captive baboons.
AB  - Baboons are an ideal model for studies of human inflammatory response due to
      their physiological and immunological similarities to people; however; little is
      known about how age affects immune function in the baboon. We sought to determine
      if baboons show age-related innate immune changes similar to that described in
      people. Age was correlated with increased serum C-reactive protein and
      interleukin-6 or, however, no change in interleukin-10 concentration was observed
      (n = 120 baboons). Cytokine release from unstimulated peripheral blood
      mononuclear cells as well as following immune (lipopolysaccharide) stimulation
      increased with age. When whole blood was assayed, both lipopolysaccharide
      stimulated and unstimulated samples showed an age-related increase in interleukin
      6 response, although the unstimulated cytokine response was reduced compared with
      that observed in peripheral blood mononuclear cells. Tumor necrosis factor-alpha
      response was not related to age. Cytokine response in lipopolysaccharide
      stimulated whole blood was negatively correlated with serum DHEA-S concentration
      and positively correlated with TGF-beta concentration.

PMID- 21860019
TI  - Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a
      murine model of Trousseau syndrome.
AB  - Trousseau syndrome is classically defined as migratory, heparin-sensitive but
      warfarin-resistant microthrombi in patients with occult, mucinous
      adenocarcinomas. Injecting carcinoma mucins into mice generates platelet-rich
      microthrombi dependent on P- and L-selectin but not thrombin. Heparin prevents
      mucin binding to P- and L-selectin and mucin-induced microthrombi. This model of
      Trousseau syndrome explains resistance to warfarin, which inhibits fluid-phase
      coagulation but not selectins. Here we found that carcinoma mucins do not
      generate microthrombi in mice lacking P-selectin glycoprotein ligand-1 (PSGL-1),
      the leukocyte ligand for P- and L-selectin. Furthermore, mucins did not activate
      platelets in blood from PSGL-1-deficient mice. Mucins induced microthrombi in
      radiation chimeras lacking endothelial P-selectin but not in chimeras lacking
      platelet P-selectin. Mucins caused leukocytes to release cathepsin G, but only if
      platelets were present. Mucins failed to generate microthrombi in cathepsin G
      deficient mice. Mucins did not activate platelets in blood from mice lacking
      cathepsin G or protease-activated receptor-4 (PAR4), indicating that cathepsin G
      activates platelets through PAR4. Using knockout mice and blocking antibodies, we
      found that mucin-triggered cathepsin G release requires L-selectin and PSGL-1 on
      neutrophils, P-selectin on platelets, and Src family kinases in both cell types.
      Thus, carcinoma mucins promote thrombosis through adhesion-dependent,
      bidirectional signaling in neutrophils and platelets.

PMID- 21860020
TI  - TNFalpha facilitates clonal expansion of JAK2V617F positive cells in
      myeloproliferative neoplasms.
AB  - Proinflammatory cytokines such as TNFalpha are elevated in patients with
      myeloproliferative neoplasms (MPN), but their contribution to disease
      pathogenesis is unknown. Here we reveal a central role for TNFalpha in promoting
      clonal dominance of JAK2(V617F) expressing cells in MPN. We show that JAK2(V617F)
      kinase regulates TNFalpha expression in cell lines and primary MPN cells and
      TNFalpha expression is correlated with JAK2(V617F) allele burden. In clonogenic
      assays, normal controls show reduced colony formation in the presence of TNFalpha
      while colony formation by JAK2(V617F)-positive progenitor cells is resistant or
      stimulated by exposure to TNFalpha. Ectopic JAK2(V617F) expression confers
      TNFalpha resistance to normal murine progenitor cells and overcomes inherent
      TNFalpha hypersensitivity of Fanconi anemia complementation group C deficient
      progenitors. Lastly, absence of TNFalpha limits clonal expansion and attenuates
      disease in a murine model of JAK2(V617F)-positive MPN. Altogether our data are
      consistent with a model where JAK2(V617F) promotes clonal selection by conferring
      TNFalpha resistance to a preneoplastic TNFalpha sensitive cell, while
      simultaneously generating a TNFalpha-rich environment. Mutations that confer
      resistance to environmental stem cell stressors are a recognized mechanism of
      clonal selection and leukemogenesis in bone marrow failure syndromes and our data
      suggest that this mechanism is also critical to clonal selection in MPN.

PMID- 21860021
TI  - Autoreactive CD1b-restricted T cells: a new innate-like T-cell population that
      contributes to immunity against infection.
AB  - Group 1 CD1 (CD1a, -b, and -c) presents self and foreign lipid antigens to
      multiple T-cell subsets in humans. However, in the absence of a suitable animal
      model, the specific functions and developmental requirements of these T cells
      remain unknown. To study group 1 CD1-restricted T cells in vivo, we generated
      double transgenic mice (HJ1Tg/hCD1Tg) that express group 1 CD1 molecules in a
      similar pattern to that observed in humans (hCD1Tg) as well as a TCR derived from
      a CD1b-autoreactive T-cell line (HJ1Tg). Using this model, we found that similar
      to CD1d-restricted NKT cells, HJ1 T cells exhibit an activated phenotype
      (CD44(hi)CD69(+)CD122(+)) and a subset of HJ1 T cells expresses NK1.1 and is
      selected by CD1b-expressing hematopoietic cells. HJ1 T cells secrete
      proinflammatory cytokines in response to stimulation with CD1b-expressing
      dendritic cells derived from humans as well as hCD1Tg mice, suggesting that they
      recognize species conserved self-lipid antigen(s). Importantly, this basal
      autoreactivity is enhanced by TLR-mediated signaling and HJ1 T cells can be
      activated and confer protection against Listeria infection. Taken together, our
      data indicate that CD1b-autoreactive T cells, unlike mycobacterial lipid antigen
      specific T cells, are innate-like T cells that may contribute to early anti
      microbial host defense.

PMID- 21860022
TI  - IL-36R ligands are potent regulators of dendritic and T cells.
AB  - IL-36alpha (IL-1F6), IL-36beta (IL-1F8), and IL-36gamma (IL-1F9) are members of
      the IL-1 family of cytokines. These cytokines bind to IL-36R (IL-1Rrp2) and IL
      1RAcP, activating similar intracellular signals as IL-1, whereas IL-36Ra (IL-1F5)
      acts as an IL-36R antagonist (IL-36Ra). In this study, we show that both murine
      bone marrow-derived dendritic cells (BMDCs) and CD4(+) T lymphocytes
      constitutively express IL-36R and respond to IL-36alpha, IL-36beta, and IL
      36gamma. IL-36 induced the production of proinflammatory cytokines, including IL
      12, IL-1beta, IL-6, TNF-alpha, and IL-23 by BMDCs with a more potent stimulatory
      effect than that of other IL-1 cytokines. In addition, IL-36beta enhanced the
      expression of CD80, CD86, and MHC class II by BMDCs. IL-36 also induced the
      production of IFN-gamma, IL-4, and IL-17 by CD4(+) T cells and cultured
      splenocytes. These stimulatory effects were antagonized by IL-36Ra when used in
      100- to 1000-fold molar excess. The immunization of mice with IL-36beta
      significantly and specifically promoted Th1 responses. Our data thus indicate a
      critical role of IL-36R ligands in the interface between innate and adaptive
      immunity, leading to the stimulation of T helper responses.

PMID- 21860023
TI  - Serological identification of HSP105 as a novel non-Hodgkin lymphoma therapeutic
      target.
AB  - We reported that the clinical efficacy of dendritic cell-based vaccination is
      strongly associated with immunologic responses in relapsed B-cell non-Hodgkin
      lymphoma (B-NHL) patients. We have now investigated whether postvaccination
      antibodies from responders recognize novel shared NHL-restricted antigens.
      Immunohistochemistry and flow cytometry showed that they cross-react with
      allogeneic B-NHLs at significantly higher levels than their matched
      prevaccination samples or nonresponders' antibodies. Western blot analysis of
      DOHH-2 lymphoma proteome revealed a sharp band migrating at approximately 100 to
      110 kDa only with postvaccine repertoires from responders. Mass spectrometry
      identified heat shock protein-105 (HSP105) in that molecular weight interval.
      Flow cytometry and immunohistochemistry disclosed HSP105 on the cell membrane and
      in the cytoplasm of B-NHL cell lines and 97 diagnostic specimens. A direct
      correlation between HSP105 expression and lymphoma aggressiveness was also
      apparent. Treatment of aggressive human B-NHL cell lines with an anti-HSP105
      antibody had no direct effects on cell cycle or apoptosis but significantly
      reduced the tumor burden in xenotransplanted immunodeficient mice. In vivo
      antilymphoma activity of HSP105 engagement was associated with a significant
      local increase of Granzyme B(+) killer cells that very likely contributed to the
      tumor-restricted necrosis. Our study adds HSP105 to the list of nononcogenes that
      can be exploited as antilymphoma targets.

PMID- 21860024
TI  - Gene induction and repression during terminal erythropoiesis are mediated by
      distinct epigenetic changes.
AB  - It is unclear how epigenetic changes regulate the induction of erythroid-specific
      genes during terminal erythropoiesis. Here we use global mRNA sequencing (mRNA
      seq) and chromatin immunoprecipitation coupled to high-throughput sequencing
      (CHIP-seq) to investigate the changes that occur in mRNA levels, RNA polymerase
      II (Pol II) occupancy, and multiple posttranslational histone modifications when
      erythroid progenitors differentiate into late erythroblasts. Among genes induced
      during this developmental transition, there was an increase in the occupancy of
      Pol II, the activation marks H3K4me2, H3K4me3, H3K9Ac, and H4K16Ac, and the
      elongation methylation mark H3K79me2. In contrast, genes that were repressed
      during differentiation showed relative decreases in H3K79me2 levels yet had
      levels of Pol II binding and active histone marks similar to those in erythroid
      progenitors. We also found that relative changes in histone modification levels,
      in particular, H3K79me2 and H4K16ac, were most predictive of gene expression
      patterns. Our results suggest that in terminal erythropoiesis both promoter and
      elongation-associated marks contribute to the induction of erythroid genes,
      whereas gene repression is marked by changes in histone modifications mediating
      Pol II elongation. Our data map the epigenetic landscape of terminal
      erythropoiesis and suggest that control of transcription elongation regulates
      gene expression during terminal erythroid differentiation.

PMID- 21860025
TI  - Impact of gene expression profiling-based risk stratification in patients with
      myeloma receiving initial therapy with lenalidomide and dexamethasone.
AB  - Detection of specific chromosomal abnormalities by FISH and metaphase
      cytogenetics allows risk stratification in multiple myeloma; however, gene
      expression profiling (GEP) based signatures may enable more specific risk
      categorization. We examined the utility of 2 GEP-based risk stratification
      systems among patients undergoing initial therapy with lenalidomide in the
      context of a phase 3 trial. Among 45 patients studied at baseline, 7 (16%) and 10
      (22%), respectively, were high-risk using the GEP70 and GEP15 signatures. The
      median overall survival for the GEP70 high-risk group was 19 months versus not
      reached for the rest (hazard ratio = 14.1). Although the medians were not
      reached, the GEP15 also predicted a poor outcome among the high-risk patients.
      The C-statistic for the GEP70, GEP15, and FISH based risk stratification systems
      was 0.74, 0.7, and 0.7, respectively. Here we demonstrate the prognostic value
      for GEP risk stratification in a group of patients primarily treated with novel
      agents. This trial was registered at www.clinicaltrials.gov as #NCT00098475.

PMID- 21860026
TI  - Cereblon expression is required for the antimyeloma activity of lenalidomide and
      pomalidomide.
AB  - The precise molecular mechanism of action and targets through which thalidomide
      and related immunomodulatory drugs (IMiDs) exert their antitumor effects remains
      unclear. We investigated the role of cereblon (CRBN), a primary teratogenic
      target of thalidomide, in the antimyeloma activity of IMiDs. CRBN depletion is
      initially cytotoxic to human myeloma cells, but surviving cells with stable CRBN
      depletion become highly resistant to both lenalidomide and pomalidomide, but not
      to the unrelated drugs bortezomib, dexamethasone, and melphalan. Acquired
      deletion of CRBN was found to be the primary genetic event differentiating
      isogenic MM1.S cell lines cultured to be sensitive or resistant to lenalidomide
      and pomalidomide. Gene expression changes induced by lenalidomide were
      dramatically suppressed in the presence of CRBN depletion, further demonstrating
      that CRBN is required for lenalidomide activity. Downstream targets of CRBN
      include interferon regulatory factor 4 (IRF4) previously reported to also be a
      target of lenalidomide. Patients exposed to, and putatively resistant to,
      lenalidomide had lower CRBN levels in paired samples before and after therapy. In
      summary, CRBN is an essential requirement for IMiD activity and a possible
      biomarker for the clinical assessment of antimyeloma efficacy.

PMID- 21860027
TI  - Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor
      for treatment of human complement alternative pathway-mediated diseases.
AB  - To selectively modulate human complement alternative pathway (CAP) activity
      implicated in a wide range of acute and chronic inflammatory conditions and to
      provide local cell surface and tissue-based inhibition of complement-induced
      damage, we developed TT30, a novel therapeutic fusion protein linking the human
      complement receptor type 2 (CR2/CD21) C3 fragment (C3frag = iC3b, C3dg, C3d)
      binding domain with the CAP inhibitory domain of human factor H (fH). TT30
      efficiently blocks ex vivo CAP-dependent C3frag accumulation on activated
      surfaces, membrane attack complex (MAC) formation and hemolysis of RBCs in a CR2
      dependent manner, and with a ~ 150-fold potency gain over fH, without
      interference of C3 activation or MAC formation through the classic and lectin
      pathways. TT30 protects RBCs from hemolysis and remains bound and detectable for
      at least 24 hours. TT30 selectively inhibits CAP in cynomolgus monkeys and is
      bioavailable after subcutaneous injection. Using a unique combination of
      targeting and effector domains, TT30 controls cell surface CAP activation and has
      substantial potential utility for the treatment of human CAP-mediated diseases.

PMID- 21860028
TI  - Targeting DC-SIGN via its neck region leads to prolonged antigen residence in
      early endosomes, delayed lysosomal degradation, and cross-presentation.
AB  - Targeting antigens to dendritic cell (DC)-specific receptors, such as DC-SIGN,
      induces potent T cell-mediated immune responses. DC-SIGN is a transmembrane C
      type lectin receptor with a long extracellular neck region and a carbohydrate
      recognition domain (CRD). Thus far, only antibodies binding the CRD have been
      used to target antigens to DC-SIGN. We evaluated the endocytic pathway triggered
      by antineck antibodies as well as their intracellular routing and ability to
      induce CD8(+) T-cell activation. In contrast to anti-CRD antibodies, antineck
      antibodies induced a clathrin-independent mode of DC-SIGN internalization, as
      demonstrated by the lack of colocalization with clathrin and the observation that
      silencing clathrin did not affect antibody internalization in human DCs.
      Interestingly, we observed that anti-neck and anti-CRD antibodies were
      differentially routed within DCs. Whereas anti-CRD antibodies were mainly routed
      to late endosomal compartments, anti-neck antibodies remained associated with
      early endosomal compartments positive for EEA-1 and MHC class I for up to 2 hours
      after internalization. Finally, cross-presentation of protein antigen conjugated
      to antineck antibodies was approximately 1000-fold more effective than
      nonconjugated antigen. Our studies demonstrate that anti-neck antibodies trigger
      a distinct mode of DC-SIGN internalization that shows potential for targeted
      vaccination strategies.

PMID- 21860029
TI  - HIV positive but not in care: a follow-up study from Thailand.
AB  - Twenty-two persons in Northern Thailand who knew of their HIV positivity but were
      not in care were identified. They had significant medical, economic, behavioral,
      and family problems. A nurse researcher carried out a 6-month intervention with
      them to (1) assess whether they would remain in contact with the researcher for 6
      months and (2) assess whether they would make positive changes in their lives.
      All 22 participants remained in contact for 6 months. A 5-step intervention
      process resulted in substantial improvements in their lives. Eleven patients
      entered care. Five needed immediate antiretroviral therapy (ART) and improved
      their CD4 counts. Six others established primary care relationships for non-HIV
      care. Twelve obtained legal, full-, or part-time employment. Eight disclosed to
      family members. Nine participants and/or family members entered counseling.
      Twelve persons publicly disclosed themselves. Twelve reported reducing or
      stopping substance abuse. Of 4 sex workers, 2 ceased engaging in that work.

PMID- 21860030
TI  - A Case of Kaposi's Sarcoma during Primary HIV-1 Infection.
AB  - The majority of cases of Kaposi's sarcoma (KS) occur at low CD4 counts during
      chronic HIV-1 infection. We present a case of KS which was diagnosed during
      primary HIV-1 infection. This report aims to draw attention that KS may occur
      early in the course of HIV-1 infection and that primary HIV-1 infection may
      rapidly progress to AIDS.

PMID- 21860032
TI  - Violence and schizophrenia.

PMID- 21860033
TI  - Molecular mechanisms in 22q11 deletion syndrome.
AB  - It is now well recognized that as well as having a characteristic facial
      dysmorphology and a range of congenital abnormalities, individuals with
      chromosome 22q11 deletion syndrome (22q11DS) have a greatly increased risk of
      developing psychosis, in particular schizophrenia. The majority of deletions span
      a large 3Mb region at 22q11. However, the presence of affected individuals
      carrying smaller deletions have not been sufficient to satisfactorily reduce the
      critical region for the behavioral phenotype beyond a ~1.5Mb region that contains
      at least 28 genes. By having a shared genetic variant that greatly increases risk
      to psychosis, individuals with 22q11DS are a relatively homogeneous population to
      study psychiatric disease. Despite this, the large volume of research performed
      over the last 15 years suggest that the mechanism by which haploinsufficiency at
      22q11 increases risk to psychiatric illness is likely to be complex and it
      remains uncertain why individuals carrying identical 22q11 deletions can present
      with such a wide range of neuropsychiatric phenotypes. This review will therefore
      consider the ways in which deletions at 22q11 are expected to increase risk to
      develop psychiatric disease by summarizing the work that has been done to
      investigate three of the most likely disease causing mechanisms: (a) gene dosage
      sensitivity; (b) unmasking of recessive alleles or functional polymorphism; and
      (c) position effect.

PMID- 21860034
TI  - Chlorpromazine for psychosis-induced aggression or agitation.

PMID- 21860035
TI  - Aggression in schizophrenia.

PMID- 21860036
TI  - Structured assessment of violence risk in schizophrenia and other psychiatric
      disorders: a systematic review of the validity, reliability, and item content of
      10 available instruments.
AB  - OBJECTIVES: To undertake a systematic review on structured violence risk
      assessment tools in individuals with schizophrenia. METHODS: A systematic search
      was conducted from 1990 to 2011 to identify violence risk assessment tools and
      studies examining their predictive validity. Item content of the identified
      instruments was analyzed, and areas under the curve (AUC) from the studies were
      extracted. In addition, an 11-item checklist was developed to assess the utility
      and psychometric properties of these tools. RESULTS: Ten risk assessment tools
      designed to predict community violence in psychiatric patients were identified,
      but only 2 studies reporting predictive validity estimates in patients with
      schizophrenia were found (median AUC = 0.69; interquartile range = 0.60-0.77).
      When inclusion criteria was broadened to include studies measuring accuracy for
      any diagnostic group, mixed evidence of predictive validity was found, with
      median AUCs ranging from 0.62 to 0.85 depending on the population. Item content
      included mostly clinical, sociodemographic, and criminal history factors. As only
      1 tool included a neurobiological item, a structured review of brain-based and
      cognitive risk factors for violence was included, and 3 clusters (neurocognitive
      ability, neurocognitive awareness, and attitudinal cognition) were identified.
      CONCLUSIONS: While a number of violence risk assessment tools exist that can be
      used to predict the likelihood of community violence in psychiatric patients,
      there is currently little direct evidence for their utility in individuals with
      schizophrenia. In addition, there is large variation in item content between
      instruments, and further research is necessary to determine whether the inclusion
      of alternative factors could improve risk assessment.

PMID- 21860037
TI  - Neurobiology of aggression and violence in schizophrenia.
AB  - There is much evidence that schizophrenia patients have an increased risk for
      aggression and violent behavior, including homicide. The neurobiological basis
      and correlates of this risk have not been much studied. While genome-wide
      association studies are lacking, a number of candidate genes have been
      investigated. By far, the most intensively studied is the catechol-O
      methyltransferase (COMT) gene on chromosome 22. COMT is involved in the
      metabolism of dopamine, a key neurotransmitter in schizophrenia pathophysiology.
      Several studies suggest that the Val158Met polymorphism of this gene affects COMT
      activity. Methionine (Met)/Met homozygote schizophrenia patients show 4- to 5
      fold lower COMT activity than valine (Val)/Val homozygotes, and some but not all
      studies have found an association with aggression and violence. Recently, a new
      functional single-nucleotide polymorphism in the COMT gene, Ala72Ser, was found
      to be associated with homicidal behavior in schizophrenia, but this finding
      warrants further replication. Studies published so far indicate that an
      association with the monoamine oxidase A, B, or tryptophan hydroxylase 1 genes is
      unlikely. Data for the brain-derived neurotrophic factor gene are conflicting and
      limited. Data from the limited number of neuroimaging studies performed to date
      are interesting. Frontal and temporal lobe abnormalities are found consistently
      in aggressive schizophrenia patients. Positron emission tomography and single
      photon-emission computed tomography (SPECT) data indicate deficits also in the
      orbitofrontal and temporal cortex. Some functional magnetic resonance imaging
      studies found a negative association of violent behavior with frontal and right
      sided inferior parietal activity. Neuroimaging studies may well help further
      elucidate the interrelationship between neurocognitive functioning, personality
      traits, and antisocial and violent behavior.

PMID- 21860038
TI  - Psychopharmacology of aggression in schizophrenia.
AB  - The management of aggression in patients with schizophrenia is a complex and
      challenging clinical dilemma. It also is greatly influenced by prevailing
      societal and medicolegal considerations regarding the perceived associations
      between violence and mental illness. This article provides a succinct account of
      a complex area and offers evidence for available treatments to reduce the
      occurrence of violent behavior among patients with schizophrenia.

PMID- 21860039
TI  - The importance of cognitive processes for the integrative treatment of persons
      with schizophrenia.

PMID- 21860041
TI  - The role of motivation for treatment success.
AB  - Learning during skills-based psychosocial treatments for schizophrenia is
      influenced by the motivating properties of the treatment context and the
      motivational orientation of the client. Given that motivational impairment is a
      core feature of schizophrenia with significant functional implications,
      intervention strategies emphasizing extrinsic and/or intrinsic goals may be
      prescribed to enhance skill learning and treatment outcomes. The purpose of this
      article is to consider the role that motivation plays in treatment success by
      evaluating the relationship between motivation and learning during cognitive
      remediation for schizophrenia. As intrinsic motivation (IM) is most often
      associated with learning, we will integrate research findings which address 3
      main questions: (1) is IM in schizophrenia static or dynamic, (2) is it possible
      to manipulate the state of being intrinsically motivated and if so do
      manipulations of IM affect learning? and (3) can motivation theory be translated
      into clinical practice? This knowledge can facilitate treatment strategies to
      address the low base rate of IM that is characteristic of schizophrenia and can
      be applied to cognitive remediation as well as other psychosocial interventions
      which require learning for treatment success.

PMID- 21860042
TI  - A pathway to personalization of integrated treatment: informatics and decision
      science in psychiatric rehabilitation.
AB  - Personalization of treatment is a current strategic goal for improving health
      care. Integrated treatment approaches such as psychiatric rehabilitation benefit
      from personalization because they involve matching diverse arrays of treatment
      options to individually unique profiles of need. The need for personalization is
      evident in the heterogeneity of people with severe mental illness and in the
      findings of experimental psychopathology. One pathway to personalization lies in
      analysis of the judgments and decision making of human experts and other
      participants as they respond to complex circumstances in pursuit of treatment and
      rehabilitation goals. Such analysis is aided by computer simulation of human
      decision making, which in turn informs development of computerized clinical
      decision support systems. This inspires a research program involving concurrent
      development of databases, domain ontology, and problem-solving algorithms, toward
      the goal of personalizing psychiatric rehabilitation through human collaboration
      with intelligent cyber systems. The immediate hurdle is to demonstrate that
      clinical decisions beyond diagnosis really do affect outcome. This can be done by
      supporting the hypothesis that a human treatment team with access to a reasonably
      comprehensive clinical database that tracks patient status and treatment response
      over time achieves better outcome than a treatment team without such access, in a
      controlled experimental trial. Provided the hypothesis can be supported, the near
      future will see prototype systems that can construct an integrated assessment,
      formulation, and rehabilitation plan from clinical assessment data and contextual
      information. This will lead to advanced systems that collaborate with human
      decision makers to personalize psychiatric rehabilitation and optimize outcome.

PMID- 21860040
TI  - Rationale and baseline characteristics of PREVENT: a second-generation
      intervention trial in subjects at-risk (prodromal) of developing first-episode
      psychosis evaluating cognitive behavior therapy, aripiprazole, and placebo for
      the prevention of psychosis.
AB  - Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have
      been found superior to control conditions as regards prevention of psychosis in
      people at-risk of first-episode psychosis. However, no large-scale trial
      evaluating the differential efficacy of CBT and antipsychotics has been performed
      yet. In PREVENT, we evaluate CBT, aripiprazole, and clinical management (CM) as
      well as placebo and CM for the prevention of psychosis in a randomized, double
      blind, placebo-controlled trial with regard to the antipsychotic intervention and
      a randomized controlled trial with regard to the CBT intervention with blinded
      ratings. The hypotheses are first that CBT and aripiprazole and CM are superior
      to placebo and CM and second that CBT is not inferior to aripiprazole and CM
      combined. The primary outcome is transition to psychosis. By November 2010, 156
      patients were recruited into the trial. The subjects were substantially
      functionally compromised (Social and Occupational Functioning Assessment Scale
      mean score 52.5) and 78.3% presented with a Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition axis I comorbid diagnosis. Prior to
      randomization, 51.5% of the participants preferred to be randomized into the CBT
      arm, whereas only 12.9% preferred pharmacological treatment. First, assessments
      of audiotaped treatment sessions confirmed the application of CBT-specific skills
      in the CBT condition and the absence of those in CM. The overall quality rating
      of the CBT techniques applied in the CBT condition was good. When the final
      results of the trial are available, PREVENT will substantially expand the current
      limited evidence base for best clinical practice in people at-risk (prodromal) of
      first-episode psychosis.

PMID- 21860043
TI  - Cognitive binding in schizophrenia: weakened integration of temporal intersensory
      information.
AB  - Cognitive functioning is based on binding processes, by which different features
      and elements of neurocognition are integrated and coordinated. Binding is an
      essential ingredient of, for instance, Gestalt perception. We have implemented a
      paradigm of causality perception based on the work of Albert Michotte, in which 2
      identical discs move from opposite sides of a monitor, steadily toward, and then
      past one another. Their coincidence generates an ambiguous percept of either
      "streaming" or "bouncing," which the subjects (34 schizophrenia spectrum patients
      and 34 controls with mean age 27.9 y) were instructed to report. The latter
      perception is a marker of the binding processes underlying perceived causality
      (type I binding). In addition to this visual task, acoustic stimuli were
      presented at different times during the task (150 ms before and after visual
      coincidence), which can modulate perceived causality. This modulation by
      intersensory and temporally delayed stimuli is viewed as a different type of
      binding (type II). We show here, using a mixed-effects hierarchical analysis,
      that type II binding distinguishes schizophrenia spectrum patients from healthy
      controls, whereas type I binding does not. Type I binding may even be excessive
      in some patients, especially those with positive symptoms; Type II binding,
      however, was generally attenuated in patients. The present findings point to ways
      in which the disconnection (or Gestalt) hypothesis of schizophrenia can be
      refined, suggesting more specific markers of neurocognitive functioning and
      potential targets of treatment.

PMID- 21860044
TI  - Negative symptoms and social cognition: identifying targets for psychological
      interventions.
AB  - BACKGROUND: How to improve treatment for negative symptoms is a continuing topic
      of debate. Suggestions have been made to advance psychological understanding of
      negative symptoms by focusing on the social cognitive processes involved in
      symptom formation and maintenance. METHODS: Following the recommendations by the
      National Institute of Mental Health workshop on social cognition in
      schizophrenia, this study investigated associations between negative symptoms and
      various aspects of social cognition including Theory of Mind (ToM), attribution,
      empathy, self-esteem, and interpersonal self-concepts in 75 patients with
      schizophrenia spectrum disorders and 75 healthy controls. RESULTS: Negative
      symptoms were significantly associated with difficulties in ToM, less readiness
      to be empathic, lower self-esteem, less self-serving bias, negative self-concepts
      related to interpersonal abilities, and dysfunctional acceptance beliefs.
      Different aspects of social cognition were mildly to moderately correlated and
      interacted in their impact on negative symptoms: Difficulties in ToM were
      associated with negative symptoms in persons with low but not in persons with
      medium or high levels of self-esteem. Taken together, the social cognition
      variables and their hypothesized interaction explained 39% of the variance in
      negative symptoms after controlling for neurocognition and depression.
      CONCLUSIONS: The results highlight the relevance of self-concepts related to
      social abilities, dysfunctional beliefs, and global self-worth alone and in
      interaction with ToM deficits for negative symptoms and thereby provide a helpful
      basis for advancing psychosocial interventions.

PMID- 21860045
TI  - Neurocognitive predictors of work outcome in recent-onset schizophrenia.
AB  - While the role of neurocognitive impairment in predicting functional outcome in
      chronic schizophrenia is now widely accepted, the results that have examined this
      relationship in the early phase of psychosis are surprisingly rather mixed. The
      predictive role of cognitive impairment early in the illness is of particular
      interest because interventions during this initial period may help to prevent the
      development of chronic disability. In a University of California, Los Angeles
      (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first
      episode of psychosis using a neurocognitive battery at an initial clinically
      stabilized outpatient point and then followed them during continuous treatment
      over the next 9 months. Three orthogonal cognitive factors were derived through
      principal components analysis: working memory, attention and early perceptual
      processing, and verbal memory and processing speed. All patients were provided a
      combination of maintenance antipsychotic medication, case management, group
      skills training, and family education in a UCLA research clinic. A modified
      version of the Social Adjustment Scale was used to assess work outcome. Multiple
      regression analyses indicate that the combination of the 3 neurocognitive factors
      predicts 52% of the variance in return to work or school by 9 months after
      outpatient clinical stabilization. These data strongly support the critical role
      of neurocognitive factors in recovery of work functioning after an onset of
      schizophrenia. Cognitive remediation and other interventions targeting these
      early cognitive deficits are of major importance to attempts to prevent chronic
      disability.

PMID- 21860046
TI  - Social cognition as a mediator variable between neurocognition and functional
      outcome in schizophrenia: empirical review and new results by structural equation
      modeling.
AB  - Cognitive impairments are currently regarded as important determinants of
      functional domains and are promising treatment goals in schizophrenia.
      Nevertheless, the exact nature of the interdependent relationship between
      neurocognition and social cognition as well as the relative contribution of each
      of these factors to adequate functioning remains unclear. The purpose of this
      article is to systematically review the findings and methodology of studies that
      have investigated social cognition as a mediator variable between neurocognitive
      performance and functional outcome in schizophrenia. Moreover, we carried out a
      study to evaluate this mediation hypothesis by the means of structural equation
      modeling in a large sample of 148 schizophrenia patients. The review comprised 15
      studies. All but one study provided evidence for the mediating role of social
      cognition both in cross-sectional and in longitudinal designs. Other variables
      like motivation and social competence additionally mediated the relationship
      between social cognition and functional outcome. The mean effect size of the
      indirect effect was 0.20. However, social cognitive domains were differentially
      effective mediators. On average, 25% of the variance in functional outcome could
      be explained in the mediation model. The results of our own statistical analysis
      are in line with these conclusions: Social cognition mediated a significant
      indirect relationship between neurocognition and functional outcome. These
      results suggest that research should focus on differential mediation pathways.
      Future studies should also consider the interaction with other prognostic
      factors, additional mediators, and moderators in order to increase the predictive
      power and to target those factors relevant for optimizing therapy effects.

PMID- 21860047
TI  - Integrative etiopathogenetic models of psychotic disorders: methods, evidence and
      concepts.
AB  - Integrative models of the etiopathogesnesis of psychotic disorders are needed
      since a wealth of information from such diverse fields as neurobiology,
      psychology, and the social sciences is currently changing the concepts of mental
      disorders. Several approaches to integrate these streams of information into
      coherent concepts of psychosis are feasible and will need to be assessed in
      future experimental studies. Common to these concepts are the notion of psychotic
      disorders as brain disorders and a polythetic approach in that it is increasingly
      realized that a multitude of interindividually partially different pathogenetic
      factors interact in individual persons in a complex fashion resulting in the
      clinical symptoms of psychosis.

PMID- 21860048
TI  - Compensatory cognitive training for psychosis: who benefits? Who stays in
      treatment?
AB  - Enhancing cognitive performance to improve functioning in schizophrenia is a
      fundamental research priority. Previous investigations have demonstrated that
      various types of cognitive training (CT) can improve neuropsychological
      performance, psychosocial functioning, and psychiatric symptom severity. However,
      there is limited information about individual differences that may predict CT
      response and adherence to treatment. The purpose of this study was to identify
      who is likely to drop out of this type of study as well as this type of
      intervention and to explore individual factors predicting treatment outcome.
      Participants included 89 outpatients diagnosed with a primary psychotic disorder
      who enrolled in a randomized controlled trial of compensatory CT and were
      assessed at baseline, 3 months (posttest), and 6 months (follow-up). Study
      completers had more formal education and lower daily doses of antipsychotic
      medications than did dropouts with no CT exposure, but the groups did not
      otherwise differ. There were no significant differences between participants who
      completed CT and those who began CT but later dropped out. CT-associated
      improvement was correlated with worse baseline scores on measures of cognitive
      performance, symptom severity, functional capacity, and self-rated quality of
      life, cognitive problems, and strategy use. These results suggest that those with
      lower baseline functioning may have more room to improve following CT. The
      pattern of correlations in this sample indicated that many types of individuals
      can improve with CT treatment, including older patients.

PMID- 21860049
TI  - Social-cognitive remediation in schizophrenia: generalization of effects of the
      Training of Affect Recognition (TAR).
AB  - In the last decade, several social cognitive remediation programs have been
      developed for use in schizophrenia. Though existing evidence indicates that such
      programs can improve social cognition, which is essential for successful social
      functioning, it remains unclear whether the improvements generalize to social
      cognitive domains not primarily addressed by the intervention and whether the
      improved test performance transfers into everyday social functioning. The present
      study investigated whether, beyond its known effects on facial affect
      recognition, the Training of Affect Recognition (TAR) has effects on prosodic
      affect recognition, theory of mind (ToM) performance, social competence in a role
      play task, and more general social and occupational functioning. Thirty-eight
      inpatients with a diagnosis of schizophrenia or schizoaffective disorder were
      randomly assigned to 6 weeks of treatment with the TAR--primarily targeted at
      facial affect recognition-or Cognitive Remediation Training (CRT)--primarily
      targeted at neurocognition. Intention-to-treat analyses found significantly
      larger pre-post improvements with TAR than with CRT in prosodic affect
      recognition, ToM, and social competence and a trend effect in global social
      functioning. However, the effects on ToM and social competence were no longer
      significant in the smaller group of patients who completed treatment according to
      protocol. Results suggest that TAR effects generalize to other social cognitive
      domains not primarily addressed. TAR may also enhance social skills and social
      functioning, although this has to be confirmed. Results are discussed with regard
      to the need to improve functional outcome in schizophrenia against the background
      of current evidence from other social cognitive remediation approaches.

PMID- 21860050
TI  - Effectiveness of integrated psychological therapy (IPT) for schizophrenia
      patients: a research update.
AB  - Standardized recovery criteria go beyond symptom remission and put special
      emphasis on personal and social functioning in residence, work, and leisure.
      Against this background, evidence-based integrated approaches combining cognitive
      remediation with social skills therapy show promise for improving functional
      recovery of schizophrenia patients. Over the past 30 years, research groups in 12
      countries have evaluated integrated psychological therapy (IPT) in 36 independent
      studies. IPT is a group therapy program for schizophrenia patients. It combines
      neurocognitive and social cognitive interventions with social skills and problem
      solving approaches. The aim of the present study was to update and integrate the
      growing amount of research data on the effectiveness of IPT. We quantitatively
      reviewed the results of these 36 studies, including 1601 schizophrenia patients,
      by means of a meta-analytic procedure. Patients undergoing IPT showed
      significantly greater improvement in all outcome variables (neurocognition,
      social cognition, psychosocial functioning, and negative symptoms) than those in
      the control groups (placebo-attention conditions and standard care). IPT patients
      maintained their mean positive effects during an average follow-up period of 8.1
      months. They showed better effects on distal outcome measures when all 5
      subprograms were integrated. This analysis summarizes the broad empirical
      evidence indicating that IPT is an effective rehabilitation approach for
      schizophrenia patients and is robust across a wide range of sample
      characteristics as well as treatment conditions. Moreover, the cognitive and
      social subprograms of IPT may work in a synergistic manner, thereby enhancing the
      transfer of therapy effects over time and improving functional recovery.

PMID- 21860051
TI  - Thinking about the future cognitive remediation therapy--what works and could we
      do better?
AB  - This article reviews progress in the development of effective cognitive
      remediation therapy (CRT) and its translational process. There is now enough
      evidence that cognitive difficulties experienced by people with schizophrenia can
      change and that the agenda for the next generation of studies is to increase
      these effects systematically through cognitive remediation. We examine the
      necessary steps and challenges of moving CRT to treatment dissemination. Theories
      which have been designed to explain the effects of cognitive remediation, are
      important but we conclude that they are not essential for dissemination which
      could progress in an empirical fashion. One apparent barrier is that cognitive
      remediation therapies look different on the surface. However, they still tend to
      use many of the same training procedures. The only important marker for outcome
      identified in the current studies seems to be the training emphasis. Some
      therapies concentrate on massed practice of cognitive functions, whereas others
      also use direct training of strategies. These may produce differing effects as
      noted in the most recent meta-analyses. We recommend attention to several
      critical issues in the next generation of empirical studies. These include
      developing more complex models of the therapy effects that take into account
      participant characteristics, specific and broad cognitive outcomes, the study
      design, as well as the specific and nonspecific effects of treatment, which have
      rarely been investigated in this empirical programme.

PMID- 21860052
TI  - Simulated job interview skill training for people with psychiatric disability:
      feasibility and tolerability of virtual reality training.
AB  - The job interview is an important step toward successful employment and often a
      significant challenge for people with psychiatric disability. Vocational
      rehabilitation specialists can benefit from a systematic approach to training job
      interview skills. The investigators teamed up with a company that specializes in
      creating simulated job interview training to create software that provides a
      virtual reality experience with which learners can systematically improve their
      job interview skills, reduce their fears, and increase their confidence about
      going on job interviews. The development of this software is described and
      results are presented from a feasibility and tolerability trial with 10
      participants with psychiatric disability referred from their vocational service
      programs. Results indicate that this representative sample had a strongly
      positive response to the prototype job interview simulation. They found it easy
      to use, enjoyed the experience, and thought it realistic and helpful. Almost all
      described the interview as anxiety provoking but that the anxiety lessened as
      they became more skilled. They saw the benefit of its special features such as
      ongoing feedback from a "coach in the corner" and from being able to review a
      transcript of the interview. They believed that they could learn the skills being
      taught through these methods. Participants were enthusiastic about wanting to use
      the final product when it becomes available. The advantages of virtual reality
      technology for training important skills for rehabilitation are discussed.

PMID- 21860053
TI  - Negative symptoms of schizophrenia as primary target of cognitive behavioral
      therapy: results of the randomized clinical TONES study.
AB  - Clinical studies on cognitive behavioral therapy (CBT) that include schizophrenia
      patients primarily on the basis of negative symptoms are uncommon. However, those
      studies are necessary to assess the efficacy of CBT on negative symptoms. This
      article first gives an overview of CBT on negative symptoms and discusses the
      methodological problems of selecting an adequate control group. Furthermore, the
      article describes a clinical study (the TONES-Study, ISRCTN 25455020), which aims
      to investigate whether CBT is specifically efficacious for the reduction of
      negative symptoms. This multicenter randomized clinical trial comparing CBT with
      cognitive remediation (CR) for control of nonspecific effects is depicted in
      detail. In our trial, schizophrenia patients (n = 198) participated in manualized
      individual outpatient treatments. Primary outcome is the negative syndrome
      assessed with the positive and negative syndrome scale, analyzed with multilevel
      linear mixed models. Patients in both groups moderately improved regarding the
      primary endpoint. However, against expectation, there was no difference between
      the groups after treatment in the intention to treat as well as in the per
      protocol analysis. In conclusion, psychotherapeutic intervention may be useful
      for the reduction of negative symptoms. However, there is no indication for
      specific effects of CBT compared with CR.

PMID- 21860054
TI  - Genomic and EST microsatellites for Rhododendron aureum (Ericaceae) and cross
      amplification in other congeneric species.
AB  - PREMISE OF THE STUDY: Our objective of this study was to develop genomic and
      expressed sequence tag (EST)-derived microsatellites for the endangered species
      Rhododendron aureum and access their transferability in R. dauricum and R.
      brachycarpum. * METHODS AND RESULTS: Twelve genomic microsatellites were isolated
      in R. aureum using the Fast Isolation by AFLP of Sequences Containing repeats
      (FIASCO) protocol and seven EST-derived microsatellites were characterized by
      screening the Rhododendron dbEST database of GenBank. The number of alleles per
      locus ranged from one to eight. The observed and expected heterozygosity varied
      from 0.00 to 1.00 and from 0.00 to 0.73, respectively. * CONCLUSIONS: A total of
      19 microsatellite loci were developed for R. aureum. Sixteen and 10 of these loci
      were successfully amplified in R. brachycarpum and R. dauricum, respectively.
      These microsatellite markers will have potential applications in genetic
      diversity and conservation genetics studies.

PMID- 21860055
TI  - Characterization of microsatellite loci in Himatanthus drasticus (Apocynaceae), a
      medicinal plant from the Brazilian savanna.
AB  - PREMISE OF THE STUDY: We developed a new set of microsatellite markers for
      studying the genome of the janaguba tree, Himatanthus drasticus (Mart.) Plumel,
      which is used in folk medicine in northeastern Brazil. These novel markers are
      being used to evaluate the effect of harvesting on the genetic structure and
      diversity of natural populations of this species. * METHODS AND RESULTS:
      Microsatellite loci were isolated from an enriched H. drasticus genomic library.
      Nine primer pairs successfully amplified polymorphic microsatellite regions, with
      an average of 8.5 alleles per locus. The average values of observed and expected
      heterozygosity were 0.456 and 0.601, respectively. * CONCLUSIONS: The
      microsatellite markers described here are valuable tools for population genetics
      studies of H. drasticus. The majority of the primers also amplified sequences in
      the genome of another species of the same genus. This new set of markers may be
      useful in designing a genetic conservation strategy and a sustainable management
      plan for the species.

PMID- 21860056
TI  - Molecular phylogenetic analysis of the Persea group (Lauraceae) and its
      biogeographic implications on the evolution of tropical and subtropical Amphi
      Pacific disjunctions.
AB  - PREMISE OF THE STUDY: The Persea group (Lauraceae) has a tropical and
      subtropical amphi-pacific disjunct distribution with most of its members, and it
      includes two Macaronesian species. The relationships within the group are still
      controversial, and its intercontinental disjunction has not been investigated
      with extensive sampling and precise time dating. * METHODS: ITS and LEAFY intron
      II sequences of 78 Persea group species and nine other Lauraceae species were
      analyzed with maximum parsimony and Bayesian inference. Divergence time
      estimation employed Bayesian Markov chain Monte Carlo method under a relaxed
      clock. * KEY RESULTS: Several traditional genera or subgenera within the Persea
      group form well-supported monophyletic groups except Alseodaphne and Dehaasia.
      The divergence time of the Persea group is estimated as ~55.3 (95% higher
      posterior densities [HPD] 41.4-69.9) million years ago (mya). Two major
      divergences within the Persea group are estimated as ~51.9 (95% HPD 38.9-63.9)
      mya and ~48.5 (95% HPD 35.9-59.9) mya. * CONCLUSIONS: Persea can be retained as a
      genus by the inclusion of Apollonias barbujana and exclusion a few species that
      do not fit into the established subgenera. A major revision is recommended for
      the delimitation between Alseodaphne, Dehaasia, and Nothaphoebe. We suggest that
      the Persea group originated from the Perseeae-Laureae radiation in early Eocene
      Laurasia. Its amphi-pacific disjunction results from the disruption of
      boreotropical flora by climatic cooling during the mid- to late Eocene. The
      American-Macaronesian disjunction may be explained by the long-distance
      dispersal.

PMID- 21860057
TI  - Evidence-based medicine in health care reform.
AB  - The Patient Protection and Affordable Care Act of 2010 mandates a national
      comparative outcomes research project agenda. Comparative effectiveness research
      includes both clinical trials and observational studies and is facilitated by
      electronic health records. A national network of electronic health records will
      create a vast electronic data "warehouse" with exponential growth of
      observational data. High-quality associations will identify research topics for
      pragmatic clinical trials, and systematic reviews of clinical trials will provide
      optimal evidence-based medicine. Evidence-based medicine is the conscientious,
      explicit, and judicious use of current best evidence in making decisions about
      the care of individual patients. Thus, health care reform will provide a robust
      environment for comparative effectiveness research, systematic reviews, and
      evidence-based medicine, and implementation of evidence-based medicine should
      lead to improved quality of care.

PMID- 21860058
TI  - Profile of patients with completion thyroidectomy and assessment of their
      suitability for outpatient surgery.
AB  - OBJECTIVE: Outpatient thyroid surgery for thyroid lobectomy has been shown to be
      safe and feasible. The safety of outpatient completion thyroidectomy in patients
      who have previously undergone thyroid lobectomy has not been extensively
      evaluated in the medical literature to date. The authors sought to evaluate
      postoperative complications associated with completion thyroidectomy in their
      institution to determine if it would be safe and feasible to perform as an
      outpatient procedure. STUDY DESIGN: Case series with chart review. SETTING:
      Tertiary care teaching hospital. SUBJECTS AND METHODS: Two hundred four
      consecutive patients, who underwent completion thyroidectomy after previous
      thyroid lobectomy from January 2000 to June 2010, comprised the study population.
      Medical records were reviewed for preoperative and postoperative serum calcium
      levels, preoperative and postoperative fiber-optic laryngoscopic examination of
      vocal fold mobility, associated comorbidities, length of hospital stay, drain
      use, seroma or hematoma formation, final thyroid pathology, and postoperative
      follow-up. RESULTS: Overall, 9 patients (4.4%) developed postoperative
      complications, including transient symptomatic hypocalcemia in 4 patients (2.0%),
      transient laboratory hypocalcemia in 3 patients (1.5%), seroma formation in 1
      patient (0.5%), and hematoma development in 1 patient (0.5%). There were no cases
      with permanent or temporary vocal fold paralysis. No significant difference was
      found in the overall complication rate before and after 4 hours of observation (P
      = .50). CONCLUSION: Selected patients who undergo completion thyroidectomy after
      previous thyroid lobectomy can be safely discharged after 4 hours of
      postoperative observation with appropriate instructions.

PMID- 21860060
TI  - What can regenerative medicine offer for infants with laryngotracheal agenesis?
AB  - BACKGROUND: Laryngotracheal agenesis is a rare congenital disorder but has
      devastating consequences. Recent achievements in regenerative medicine have
      opened up new vistas in therapeutic strategies for these infants. OBJECTIVE: To
      provide a state-of-the-art review concerning recent achievements in tissue
      engineering as applied to fetal airway reconstruction and to discuss the use of
      autologous human amniotic stem cells to prepare organs in advance for babies with
      laryngotracheal agenesis. DATA SOURCES AND REVIEW METHODS: A structured search of
      the current literature (up to and including June 2011). The authors searched
      PubMed, EMBASE, CINAHL, Web of Science, BIOSIS Previews, Cambridge Scientific
      Abstracts, ICTRP, and additional sources for published and unpublished trials.
      RESULTS: Over the past 15 years, progress has been made in advancing the
      boundaries of regenerative medicine from the laboratory to the clinical setting
      through translational research. Most experience has been gained with adult stem
      cells and synthetic materials or decellularized scaffolds. The optimal cell
      source for fetal tissue engineering remains to be determined, but a combination
      of decellularized scaffolds and amniotic fluid stem cells holds great promise for
      fetal tissue engineering. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Current
      treatment strategies for laryngotracheal agenesis are suboptimal, and fetal
      tissue engineering offers an alternative to conventional treatments. Use of human
      amniotic fluid stem cells for preparing autologous tissue-engineered organ
      constructs prenatally is an attractive concept. Although this approach is still
      in its experimental stages, further preclinical and clinical studies are
      encouraged to define its exact role in the pediatric laryngological setting.

PMID- 21860059
TI  - Is ototopical nystatin ototoxic? A chinchilla model.
AB  - In this prospective controlled animal study, the authors investigated the
      potential ototoxic effects of ototopical application of nystatin through a
      tympanostomy tube, using their established chinchilla animal model. Each of the
      10 animals used had ventilation tubes inserted in both ears; 1 ear was randomly
      assigned to receive nystatin suspension, whereas the other ear did not receive
      any medication, serving as control. Distortion product otoacoustic emissions
      (DPOAEs) were measured in each animal before application of nystatin and at 45
      and 60 days after application. Each cochlea was also processed for scanning
      electron microscopy (SEM) at the end of the experiment. There was no significant
      difference in the DPOAEs and SEM appearances of the experimental and control ears
      over the 60-day period of the experiment. The authors conclude that transtympanic
      nystatin did not produce any long-term ototoxic effects detectable by DPOAEs or
      SEM.

PMID- 21860061
TI  - Parotidectomy by periauricular incision.
AB  - OBJECTIVE: According to the literature, periauricular combined with submandibular
      or cervical incision is used in nearly every parotidectomy. The aim of this study
      was to present the results of the use of only periauricular incision in parotid
      surgical procedures. DESIGN: A case series with planned data collection. SETTING:
      Patients of the author were operated on at the Hospital Santa Casa de
      Misericordia de Belo Horizonte, Brazil. SUBJECTS AND METHODS: Forty-one
      consecutive partial or total parotidectomies (27 cases of pleomorphic adenoma, 9
      of other benign tumors, 3 of parotid cysts, and 2 of chronic parotiditis) were
      performed using only periauricular incision. RESULTS: The parotid tumors were
      removed in all cases with no need for any further skin procedures, as the
      incisions produced a good aesthetic result. All patients presented temporary
      hypoesthesia in the area that had been operated on for no more than 6 months. Ear
      discomfort was reported by 18 patients for a short period of time. Local
      infection occurred in 1 case successfully treated with systemic antibiotics.
      CONCLUSION: The results of the present study indicate that periauricular incision
      is a high-quality and highly aesthetic option for surgical procedures concerning
      benign conditions of the parotid gland.

PMID- 21860062
TI  - A deformable surface model for real-time water drop animation.
AB  - A water drop behaves differently from a large water body because of its strong
      viscosity and surface tension under the small scale. Surface tension causes the
      motion of a water drop to be largely determined by its boundary surface.
      Meanwhile, viscosity makes the interior of a water drop less relevant to its
      motion, as the smooth velocity field can be well approximated by an interpolation
      of the velocity on the boundary. Consequently, we propose a fast deformable
      surface model to realistically animate water drops and their flowing behaviors on
      solid surfaces. Our system efficiently simulates water drop motions in a
      Lagrangian fashion, by reducing 3D fluid dynamics over the whole liquid volume to
      a deformable surface model. In each time step, the model uses an implicit mean
      curvature flow operator to produce surface tension effects, a contact angle
      operator to change droplet shapes on solid surfaces, and a set of mesh
      connectivity updates to handle topological changes and improve mesh quality over
      time. Our numerical experiments demonstrate a variety of physically plausible
      water drop phenomena at a real-time rate, including capillary waves when water
      drops collide, pinch-off of water jets, and droplets flowing over solid
      materials. The whole system performs orders-of-magnitude faster than existing
      simulation approaches that generate comparable water drop effects.

PMID- 21860063
TI  - Using aging to visually uncover evolutionary processes on networks.
AB  - Networks are widely used to describe many natural and technological systems.
      Understanding how these evolve over time poses a challenge for existing
      visualization techniques originally developed for fixed network structures. We
      describe a method of incorporating the concept of aging into evolving networks,
      where nodes and edges store information related to the amount of local
      evolutionary change they have experienced. This property is used to generate
      visualizations that ensure stable substructures maintain relatively fixed spatial
      positions, allowing them to act as visual markers and providing context for
      evolutionary change elsewhere. By further supplementing these visualizations with
      color cues, the resultant animations enable a clearer portrayal of the underlying
      evolutionary process.

PMID- 21860064
TI  - Identifying bacterial virulent proteins by fusing a set of classifiers based on
      variants of Chou's pseudo amino acid composition and on evolutionary information.
AB  - The availability of a reliable prediction method for prediction of bacterial
      virulent proteins has several important applications in research efforts targeted
      aimed at finding novel drug targets, vaccine candidates, and understanding
      virulence mechanisms in pathogens. In this work, we have studied several feature
      extraction approaches for representing proteins and propose a novel bacterial
      virulent protein prediction method, based on an ensemble of classifiers where the
      features are extracted directly from the amino acid sequence and from the
      evolutionary information of a given protein. We have evaluated and compared
      several ensembles obtained by combining six feature extraction methods and
      several classification approaches based on two general purpose classifiers (i.e.,
      Support Vector Machine and a variant of input decimated ensemble) and their
      random subspace version. An extensive evaluation was performed according to a
      blind testing protocol, where the parameters of the system are optimized using
      the training set and the system is validated in three different independent data
      sets, allowing selection of the most performing system and demonstrating the
      validity of the proposed method. Based on the results obtained using the blind
      test protocol, it is interesting to note that even if in each independent data
      set the most performing stand-alone method is not always the same, the fusion of
      different methods enhances prediction efficiency in all the tested independent
      data sets.

PMID- 21860065
TI  - SimBioNeT: a simulator of biological network topology.
AB  - Studying biological networks at topological level is a major issue in
      computational biology studies and simulation is often used in this context,
      either to assess reverse engineering algorithms or to investigate how topological
      properties depend on network parameters. In both contexts, it is desirable for a
      topology simulator to reproduce the current knowledge on biological networks, to
      be able to generate a number of networks with the same properties and to be
      flexible with respect to the possibility to mimic networks of different
      organisms. We propose a biological network topology simulator, SimBioNeT, in
      which module structures of different type and size are replicated at different
      level of network organization and interconnected, so to obtain the desired degree
      distribution, e.g., scale free, and a clustering coefficient constant with the
      number of nodes in the network, a typical characteristic of biological networks.
      Empirical assessment of the ability of the simulator to reproduce characteristic
      properties of biological network and comparison with E. coli and S. cerevisiae
      transcriptional networks demonstrates the effectiveness of our proposal.

PMID- 21860066
TI  - Inhibition of Wnt signaling and cancer stem cells.

PMID- 21860067
TI  - The GLI genes as the molecular switch in disrupting Hedgehog signaling in colon
      cancer.
AB  - The Hedgehog (HH) signaling pathway leads to activation of GLI, which
      transcriptionally regulate target genes. Regulated HH signaling activity is
      critical during embryogenesis while aberrantly activated HH signaling is evident
      in a variety of human cancers. Canonical HH signaling engages the transmembrane
      receptor Patched (PTCH) and the signaling intermediate Smoothened (SMO) to
      activate GLI1 and GLI2. In addition GLI1 and GLI2 are activated by non-canonical
      oncogenic signaling pathways to further drive HH-dependent survival. We have
      demonstrated in human colon carcinoma cells that inhibition of the RAS/RAF
      pathway by U0126 decreases p-ERK protein expression and also inhibits GLI
      luciferase activity and GLI1 mRNA and protein levels. Of importance is the
      demonstration that targeting of SMO (using cyclopamine) has minimal effect on
      cell survival in comparison to the inhibition of GLI (using GANT61), which
      induced extensive cell death in 7/7 human colon carcinoma cell lines. Genetic
      inhibition of the function of GLI1 and GLI2 by transient transfection of the C
      terminus deleted repressor GLI3R, reduced proliferation and induced cleavage of
      caspase-3 and cell death in HT29 cells, similar to the effects of GANT61.
      Mechanistically, downstream of GLI1 and GLI2 inhibition, gammaH2AX (a marker of
      DNA double strand breaks) expression was upregulated, and gammaH2AX nuclear foci
      were demonstrated in cells that expressed GLI3R. Activation of the ATM/Chk2 axis
      with co-localization of gammaH2AX and p-Chk2 nuclear foci were demonstrated
      following GLI1/GLI2 inhibition. GANT61 induced cellular accumulation at G1/S and
      early S with no further progression before cells became subG1, while cDNA
      microarray gene profiling demonstrated downregulation of genes involved in DNA
      replication, the DNA damage response, and DNA repair, mechanisms that are
      currently being pursued. These studies highlight the importance of targeting the
      GLI genes downstream of SMO for terminating HH-dependent survival, suggesting
      that GLI may constitute a molecular switch that determines the balance between
      cell survival and cell death in human colon carcinoma.

PMID- 21860068
TI  - Anti-influenza virus activity of tricin, 4',5,7-trihydroxy-3',5'
      dimethoxyflavone.
AB  - BACKGROUND: We examined the anti-influenza virus activity of tricin, 4',5,7
      trihydroxy-3',5'-dimethoxyflavone, against five viruses: A/Solomon islands/3/2006
      (H1N1), A/Hiroshima/52/2005 (H3N2), A/California/07/2009 (H1N1pdm),
      A/Narita/1/2009 (H1N1pdm) and B/Malaysia/2506/2004 strains in vitro and against
      A/PR/8/34 virus in vivo. METHODS: The effect of tricin was studied by an
      infectious virus yield reduction assay. The anti-influenza virus mechanism of the
      tricin was examined by western blot analysis, real-time reverse transcriptase PCR
      analysis, haemagglutination inhibition (HI) assay and neuraminidase (NA)
      inhibition assay. The anti-influenza virus efficacy of tricin was further
      examined in a murine influenza virus infection model. RESULTS: Tricin of 3.3 to
      30 MUM significantly reduced seasonal A (H1N1), (H3N2) viruses, novel A (H1N1pdm)
      virus, as well as B virus in a dose-dependent manner. The 50% effective
      concentrations of tricin were 3.4 MUM for seasonal A (H3N2) virus, 4.9 MUM for B
      virus and 8.2 MUM for A/Narita (H1N1pdm) virus. Tricin decreased the expression
      of haemagglutinin (HA) protein and matrix (M) protein, and messenger RNA
      expression of HA and M of influenza virus in the infected cells. Tricin exhibited
      little or no effects on influenza virus HI and NA activities. In the mouse
      infection model, tricin was significantly effective in reducing body weight loss,
      and also effective in prolonging survival times of infected mice. CONCLUSIONS:
      Tricin was indicated to possess anti-influenza virus activity and to ameliorate
      body weight loss and survival rate of influenza-A-virus-infected mice. Tricin is
      a novel compound with potential anti-influenza virus activity in vitro and in
      vivo.

PMID- 21860069
TI  - The YMDD and rtA194T mutations result in decreased replication capacity in wild
      type HBV as well as in HBV with precore and basal core promoter mutations.
AB  - BACKGROUND: A recent study indicated that addition of the hepatitis B e antigen
      (HBeAg) precore (PC) or basal core promoter (BCP) mutations to wild-type HBV
      offset the reduced replication of the HBV polymerase rtA194T+/-rtL180M+rtM204V
      mutations. rtA194T was reportedly associated with tenofovir resistance. We
      investigated these findings in genotype D HBV, where both PC and BCP naturally
      occur in vivo. METHODS: A plasmid containing a wild-type 1.3 genome length
      genotype D HBV laboratory strain was used as a parent for PC, BCP, rtA194T+/
      rtL180M+rtM204V, rtL180M+rtM204V and rtM204I mutants. Viral replication was
      evaluated by Southern blot analysis of intracellular HBV core DNA following
      transient transfection of HepG2 cells. Drug susceptibility was evaluated by
      quantitative PCR of intracellular HBV DNA. RESULTS: PC and BCP mutations each
      increased HBV DNA replication by approximately 200% over wild-type. rtA194T
      reduced replication by <40%, whereas rtL180M+rtM204V, rtL180M+rtA194T+rtM204V or
      rtM204I each reduced by >75% from their respective wild-type, PC or BCP genome
      backbone (P<0.05). The enhanced replication by PC or BCP offset the reduction by
      rtA194T; however, the other reverse transcriptase (RT) mutations in PC or BCP
      backbones remained significantly lower than wild-type (P<0.05). Regardless of the
      backbone, rtA194T+/-rtL180M+rtM204V remained susceptible to tenofovir in vitro.
      rtA194T alone remained susceptible to lamivudine, while rtL180M+rtM204V and
      rtL180M+rtA194T+rtM204V were resistant. CONCLUSIONS: PC or BCP mutations
      increased HBV DNA replication, offset the decreased replication by rtA194T alone,
      but they did not fully rescue the impaired replication conferred by other RT
      mutations as compared with wild-type. rtA194T+/-rtL180M+rtM204V did not confer
      tenofovir resistance.

PMID- 21860070
TI  - Nucleotide prodrugs for HCV therapy.
AB  - HCV infection is a significant worldwide health problem and is a major cause of
      hepatocellular carcinoma. The current standard of care, interferon and ribavirin,
      is only effective against a proportion of the patient population infected with
      HCV. To address the shortcomings of existing therapy, the development of direct
      acting antiviral agents is under investigation. The HCV RNA dependent RNA
      polymerase is an essential enzyme for viral replication and is therefore a
      logical target against which to develop novel anti-HCV agents. Nucleosides have
      been shown to be effective as antiviral agents for other viral diseases and
      therefore, have been investigated as inhibitors of HCV replication. The
      development of prodrugs of nucleoside 5'-monophosphates has been pursued to
      address limitations associated with poor nucleoside phosphorylation. This is
      required to produce the nucleoside 5'-triphosphate which is the anabolite that is
      the actual inhibitor of the polymerase enzyme. Prodrugs of nucleoside 5'
      monophosphates have been developed that enable their delivery into cells and in
      vivo into the liver. The implementation of these prodrug strategies has
      ultimately led to the identification of several prodrugs of nucleoside 5'
      monophosphates that are potent inhibitors of HCV replication in vitro. They have
      progressed into the clinic and the early data demonstrate greatly reduced viral
      load levels in HCV-infected patients. This review will survey the state of
      nucleotide prodrugs for the treatment of HCV.

PMID- 21860072
TI  - Tracking the energies of one-dimensional sub-band edges in quantum point contacts
      using dc conductance measurements.
AB  - The semiconductor quantum point contact has long been a focal point for studies
      of one-dimensional (1D) electron transport. Their electrical properties are
      typically studied using ac conductance methods, but recent work has shown that
      the dc conductance can be used to obtain additional information, with a density
      dependent Lande effective g-factor recently reported (Chen et al 2009 Phys. Rev.
      B 79 081301). We discuss previous dc conductance measurements of quantum point
      contacts, demonstrating how valuable additional information can be extracted from
      the data. We provide a comprehensive and general framework for dc conductance
      measurements that provides a path to improving the accuracy of existing data and
      obtaining useful additional data. A key aspect is that dc conductance
      measurements can be used to map the energy of the 1D sub-band edges directly,
      giving new insight into the physics that takes place as the spin-split 1D sub
      bands populate. Through a re-analysis of the data obtained by Chen et al, we
      obtain two findings. The first is that the 2? sub-band edge closely tracks the
      source chemical potential when it first begins populating before dropping more
      rapidly in energy. The second is that the 2? sub-band populates more rapidly as
      the sub-band edge approaches the drain potential. This second finding suggests
      that the spin-gap may stop opening, or even begin to close again, as the 2? sub
      band continues populating, consistent with recent theoretical calculations and
      experimental studies.

PMID- 21860071
TI  - Potent anti-HIV-1 activity of N-HR-derived peptides including a deep pocket
      forming region without antagonistic effects on T-20.
AB  - BACKGROUND: Enfuvirtide (T-20), a C-terminal heptad repeat (C-HR)-derived peptide
      of HIV-1 glycoprotein, gp41, effectively suppresses HIV-1 replication through a
      putative mechanism that involves it acting as a decoy and binding to the N
      terminal heptad repeat (N-HR) of the virus. In this study, we address whether the
      anti-HIV-1 activity of T-20 is antagonized by a variety of N-HR-derived peptides.
      METHODS: Multinuclear activation of galactosidase indicator assays were used to
      evaluate T-20 activity in the presence of N-HR-derived peptides. The gp41-derived
      peptides were chemically synthesized. RESULTS: We demonstrate additive anti-HIV
      activity when T-20 is used in combination with N-HR-derived peptides that do not
      have a putative binding region for the tryptophan-rich domain in T-20. The
      presence of a deep pocket-forming region in the N-HR-derived peptides enhanced
      their anti-HIV-1 activity, but had little effect on the activity of T-20.
      CONCLUSIONS: These results indicate that T-20-based antiviral therapies can be
      combined with N-HR-derived peptides.

PMID- 21860073
TI  - Plasmon cross transmission.
AB  - Plasmon cross transmission avoids the frontal collision between two plasmons
      traveling in opposite directions along a guide. The guide is made out of
      equidistant identical metal dots. Thanks to two resonator dots, the plasmon
      frontal impact is avoided by transmission of the two plasmons from the input
      guide to an output one. The resonator and guide dots are identical in size and
      metal composition. The dipole-dipole interactions are restricted to first nearest
      neighbors. A convenient metal doping is assumed to compensate exactly all
      attenuations. The parameters are the nearest neighbor distances between the dots.
      These distances are rescaled to the chain nearest neighbor distance d. The system
      has two symmetry mirror planes. This simple model enables us to obtain two
      analytic tuning relations for the plasmon cross transmission. The intensities of
      the transmitted signals versus kd, where k is the plasmon propagation vector, are
      also given.

PMID- 21860074
TI  - High pressure investigations of Na0.025WO3: x-ray diffraction and Raman
      spectroscopy studies.
AB  - High pressure x-ray diffraction and Raman spectroscopy studies have been carried
      out on non-stoichiometric sodium tungsten bronze, Na(0.025)WO(3). The high
      pressure investigations reveal a phase transition at about 2 GPa by a change of
      space group symmetry from P2(1)/n to P2(1)/c in the monoclinic cell followed by a
      second structural transformation to a triclinic lattice around 18 GPa. There are
      volume changes with these structural transformations, which are driven by
      rotation and significant distortion of WO(6) octahedra due to the displacement of
      tungsten and oxygen atoms from their mean positions in the unit cell.

PMID- 21860075
TI  - Thermal expansion and transformation behavior of cerium and plutonium alloys: an
      application of the Aptekar-Ponyatovsky regular solution model.
AB  - In this paper we apply the Aptekar-Ponyatovsky (AP) regular solution
      thermodynamic model to the analysis of experimental data for the coefficient of
      thermal expansion (CTE) and determine the AP model parameters for unalloyed
      cerium metal, Ce-Th-La alloys, and Pu-Ga alloys. We find that the high
      temperature CTE of cerium metal follows the predictions of the AP model based on
      low temperature, high pressure data. For Ce-Th-La alloys we use the AP parameters
      to track the suppression of the first-order gamma-alpha cerium transition. We
      show the AP model accounts for the negative CTE observed for Pu-Ga alloys and is
      equivalent to an earlier invar model. Finally, we apply the AP parameters
      obtained for Pu-Ga alloys to rationalize the observed delta-alpha transformation
      pressures of these alloys. We show that the anomalous values of the Gruneisen and
      Gruneisen-Anderson parameters are important features of the thermal properties of
      plutonium. A strong analogy between the properties of plutonium and cerium is
      confirmed.

PMID- 21860076
TI  - Low-dose CT reconstruction via edge-preserving total variation regularization.
AB  - High radiation dose in computed tomography (CT) scans increases the lifetime risk
      of cancer and has become a major clinical concern. Recently, iterative
      reconstruction algorithms with total variation (TV) regularization have been
      developed to reconstruct CT images from highly undersampled data acquired at low
      mAs levels in order to reduce the imaging dose. Nonetheless, the low-contrast
      structures tend to be smoothed out by the TV regularization, posing a great
      challenge for the TV method. To solve this problem, in this work we develop an
      iterative CT reconstruction algorithm with edge-preserving TV (EPTV)
      regularization to reconstruct CT images from highly undersampled data obtained at
      low mAs levels. The CT image is reconstructed by minimizing energy consisting of
      an EPTV norm and a data fidelity term posed by the x-ray projections. The EPTV
      term is proposed to preferentially perform smoothing only on the non-edge part of
      the image in order to better preserve the edges, which is realized by introducing
      a penalty weight to the original TV norm. During the reconstruction process, the
      pixels at the edges would be gradually identified and given low penalty weight.
      Our iterative algorithm is implemented on graphics processing unit to improve its
      speed. We test our reconstruction algorithm on a digital NURBS-based cardiac
      troso phantom, a physical chest phantom and a Catphan phantom. Reconstruction
      results from a conventional filtered backprojection (FBP) algorithm and a TV
      regularization method without edge-preserving penalty are also presented for
      comparison purposes. The experimental results illustrate that both the TV-based
      algorithm and our EPTV algorithm outperform the conventional FBP algorithm in
      suppressing the streaking artifacts and image noise under a low-dose context. Our
      edge-preserving algorithm is superior to the TV-based algorithm in that it can
      preserve more information of low-contrast structures and therefore maintain
      acceptable spatial resolution.

PMID- 21860077
TI  - Image registration and analysis for quantitative myocardial perfusion:
      application to dynamic circular cardiac CT.
AB  - Large area detector computed tomography systems with fast rotating gantries
      enable volumetric dynamic cardiac perfusion studies. Prospectively, ECG-triggered
      acquisitions limit the data acquisition to a predefined cardiac phase and thereby
      reduce x-ray dose and limit motion artefacts. Even in the case of highly accurate
      prospective triggering and stable heart rate, spatial misalignment of the cardiac
      volumes acquired and reconstructed per cardiac cycle may occur due to small
      motion pattern variations from cycle to cycle. These misalignments reduce the
      accuracy of the quantitative analysis of myocardial perfusion parameters on a per
      voxel basis. An image-based solution to this problem is elastic 3D image
      registration of dynamic volume sequences with variable contrast, as it is
      introduced in this contribution. After circular cone-beam CT reconstruction of
      cardiac volumes covering large areas of the myocardial tissue, the complete
      series is aligned with respect to a chosen reference volume. The results of the
      registration process and the perfusion analysis with and without registration are
      evaluated quantitatively in this paper. The spatial alignment leads to improved
      quantification of myocardial perfusion for three different pig data sets.

PMID- 21860078
TI  - Difference-frequency generation in vibro-acoustography.
AB  - Vibro-acoustography (VA) is a medical imaging method based on the nonlinear
      interaction of two or more distinct ultrasound beams whose frequencies differ by
      several kHz. In turn, the interacting waves produce a difference-frequency signal
      which carries the information of the imaged tissue region. Two mechanisms are
      responsible for the difference-frequency generation (DFG) in VA, namely the
      dynamic (oscillatory) radiation force and the scattering of sound-by-sound. The
      role and importance of each phenomenon in VA is assessed here. A theoretical
      model based on Westervelt's equation for the DFG in the nonlinear scattering of
      two incident ultrasound waves by a small rigid sphere (compared to the incident
      wavelengths) is presented. Furthermore, a scattering experiment using VA is
      devised and the data show very good agreement with the proposed theory. The
      results reveal that the effect of scattering of sound-by-sound is the dominant
      component in the DFG in VA rather than the dynamic radiation force.

PMID- 21860079
TI  - Computerized three-class classification of MRI-based prognostic markers for
      breast cancer.
AB  - The purpose of this study is to investigate whether computerized analysis using
      three-class Bayesian artificial neural network (BANN) feature selection and
      classification can characterize tumor grades (grade 1, grade 2 and grade 3) of
      breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC
      grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected.
      The computer automatically segmented the lesions, and kinetic and morphological
      lesion features were automatically extracted. The discrimination tasks-grade 1
      versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions-were
      investigated. Step-wise feature selection was conducted by three-class BANNs.
      Classification was performed with three-class BANNs using leave-one-lesion-out
      cross-validation to yield computer-estimated probabilities of being grade 3
      lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to
      evaluate the performances. We achieved AUC values of 0.80 +/- 0.05, 0.78 +/- 0.05
      and 0.62 +/- 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2
      versus grade 3, respectively. This study shows the potential for (1) applying
      three-class BANN feature selection and classification to CADx and (2) expanding
      the role of DCE-MRI CADx from diagnostic to prognostic classification in
      distinguishing tumor grades.

PMID- 21860080
TI  - Optimal material discrimination using spectral x-ray imaging.
AB  - Spectral x-ray imaging using novel photon counting x-ray detectors (PCDs) with
      energy resolving abilities is capable of providing energy-selective images. PCDs
      have energy thresholds, enabling the classification of photons into multiple
      energy bins. The extra energy information provided may allow materials such as
      iodine and calcium, or water and fat to be distinguishable. The information
      content of spectral x-ray images, however, depends on how the photons are grouped
      together. In this work, we present a model to optimize energy windows for maximum
      material discrimination. Multivariate statistics allows the confidence region of
      the correlated uncertainties to be mapped in the thickness space. Minimization of
      the uncertainties enables optimization of energy windows. Applications related to
      small animal imaging and breast imaging are considered.

PMID- 21860081
TI  - Fabrication of a Au/Si nanocomposite structure by nanosecond pulsed laser
      irradiation.
AB  - A gold/silicon nanocomposite structure (NCS) was formed on a Si(100) surface by
      nanosecond pulsed laser irradiation. The Au/Si NCS contained both Au
      nanoparticles (NPs) and Au-Si alloy layers. We report that the use of laser
      irradiation to form Au NPs comprises two competing processes: a top-down effect
      involving decomposition into smaller NPs and a bottom-up effect involving self
      assembly or self-organization into larger NPs. The formation of the periodic
      structure involved self-organization, i.e., the bottom-up effect, and was
      observed in situ using a pulsed-laser-equipped high-voltage electron microscope.
      The NCS formed by laser irradiation can be controlled by adjusting the laser
      energy density and the number of laser pulses.

PMID- 21860082
TI  - Cu@C composite nanotube array and its application as an enzyme-free glucose
      sensor.
AB  - We report a novel hydrothermal method for the synthesis of a Cu@C nanotube array
      on a centimeter-scale substrate for the first time. In this hydrothermal reaction
      process, employing the carbon coated ZnO nanorod array as an inexpensive and
      partially sacrificial template, along with the ZnO dissolving in the alkaline
      atmosphere, the formed Cu particles deposit and grow on the carbon surface
      gradually. Importantly, the carbon shell of the template is not only essential to
      the preservation of the array configuration, but also makes a significant
      contribution to the final nanostructure. Such a method provides a morphology
      reservation transformation when various shaped carbon-containing templates are
      adopted. Moreover, this designed Cu@C array has been demonstrated as an excellent
      electrode material for an enzyme-free glucose sensor in terms of sensitivity
      (1200 uA mM( - 1) cm( - 2)) and significantly lower applied potential (-0.2 V).
      Our results present the first preparation of the Cu@C composite nanotube array
      and may open up an opportunity for rational design of advanced electrode
      materials for enzyme-free glucose sensors.

PMID- 21860083
TI  - High performance multilayered nano-crystalline silicon/silicon-oxide light
      emitting diodes on glass substrates.
AB  - A low-temperature hydrogenation-assisted sequential deposition and
      crystallization technique is reported for the preparation of nano-scale silicon
      quantum dots suitable for light-emitting applications. Radio-frequency plasma
      enhanced deposition was used to realize multiple layers of nano-crystalline
      silicon while reactive ion etching was employed to create nano-scale features.
      The physical characteristics of the films prepared using different plasma
      conditions were investigated using scanning electron microscopy, transmission
      electron microscopy, room temperature photoluminescence and infrared
      spectroscopy. The formation of multilayered structures improved the photon
      emission properties as observed by photoluminescence and a thin layer of silicon
      oxy-nitride was then used for electrical isolation between adjacent silicon
      layers. The preparation of light-emitting diodes directly on glass substrates has
      been demonstrated and the electroluminescence spectrum has been measured.

PMID- 21860085
TI  - Regional comparison of the neurogenic effects of CNTF-derived peptides and
      cerebrolysin in AbetaPP transgenic mice.
AB  - Adult neurogenesis, the production of new neurons in certain brain regions, is
      known to decrease with age and the loss of neurogenic potential has been
      implicated in Alzheimer's disease (AD), a leading cause of dementia in the
      elderly. Cerebrolysin (CBL) has been shown to increase neurogenesis in models of
      stroke and AD. CBL is composed of small peptides with activity similar to
      neurotrophic factors including ciliary neurotrophic factor (CNTF), which may
      mediate its neurogenic effects. This study compares the effects of CBL and two
      peptides with corresponding to an active region of CNTF (Peptide 6 and 6A) across
      neurogenic brain regions in amyloid-beta protein precursor (AbetaPP) transgenic
      (tg) mice. Both CBL and Peptides 6 and 6A were able to increase the numbers of
      neuroblasts (DCX+ cells) and BrdU+ cells in a regionally specific manner across
      the subventricular zone, olfactory bulb, and hippocampus. The increased
      generation of new cells and cell survival in animals treated with Peptides 6 and
      6A was accompanied by an increase in PCNA+ cells. In contrast, AbetaPP tg mice
      treated with CBL displayed reduced levels of TUNEL staining, while levels of PCNA
      were unaltered. Collectively these results demonstrate that while CBL and
      Peptides 6 and 6A all potentiate neurogenesis in the AbetaPP tg mice, their
      relative modes of action may differ with CBL associated with reduced apoptosis
      and Peptides 6 and 6A working by augmenting cell proliferation. These results are
      consistent with a potential therapeutic relevance for Peptides 6 and 6A in AD and
      other disorders characterized by neurogenic deficits.

PMID- 21860086
TI  - Biochemical and morphological characterization of the AbetaPP/PS/tau triple
      transgenic mouse model and its relevance to sporadic Alzheimer's disease.
AB  - Transgenic (Tg) mouse models of Alzheimer's disease (AD) have been genetically
      altered with human familial AD genes driven by powerful promoters. However, a Tg
      model must accurately mirror the pathogenesis of the human disease, not merely
      the signature amyloid and/or tau pathology, as such hallmarks can arise via
      multiple convergent or even by pathogenic mechanisms unrelated to human sporadic
      AD. The 3 * Tg-AD mouse simultaneously expresses 3 rare familial mutant genes
      that in humans independently produce devastating amyloid-beta protein precursor
      (AbetaPP), presenilin-1, and frontotemporal dementias; hence, technically
      speaking, these mice are not a model of sporadic AD, but are informative in
      assessing co-evolving amyloid and tau pathologies. While end-stage amyloid and
      tau pathologies in 3 * Tg-AD mice are similar to those observed in sporadic AD,
      the pathophysiological mechanisms leading to these lesions are quite different.
      Comprehensive biochemical and morphological characterizations are important to
      gauge the predictive value of Tg mice. Investigation of AbetaPP, amyloid-beta
      (Abeta), and tau in the 3 * Tg-AD model demonstrates AD-like pathology with some
      key differences compared to human sporadic AD. The biochemical dissection of
      AbetaPP reveals different cleavage patterns of the C-terminus of AbetaPP when
      compared to human AD, suggesting divergent pathogenic mechanisms. Human tau is
      concomitantly expressed with AbetaPP/Abeta from an early age while abundant
      extracellular amyloid plaques and paired helical filaments are manifested from 18
      months on. Understanding the strengths and limitations of Tg mouse AD models
      through rigorous biochemical, pathological, and functional analyses will
      facilitate the derivation of models that better approximate human sporadic AD.

PMID- 21860087
TI  - Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of
      metalloproteinases in combination with subcortical and cortical biomarkers in
      vascular dementia and Alzheimer's disease.
AB  - Alzheimer's disease (AD) and vascular dementia (VaD) are intertwined by mixed
      dementia (MD) harboring varying degrees of AD pathology in combination with
      cerebrovascular disease. The aim was to assess whether there is a difference in
      the cerebrospinal fluid (CSF) profile, of selected proteins, between patients
      with VaD and MD with subcortical vascular disease (SVD), AD, and healthy controls
      that could contribute in the separation of the groups. The study included 30
      controls, 26 SVD patients (9 VaD and 17 MD) and 30 AD patients. The protein panel
      included total tau (T-tau), hyperphosphorylated tau 181 (P-tau(181)), amyloid
      beta 1-42 (Abeta(1-42)), neurofilament light (NF-L), myelin basic protein (MBP),
      heart fatty acid binding protein (H-FABP), matrix metalloproteinases (MMP-1, -2, 
      3, -9, and -10), and tissue inhibitors of metalloproteinases (TIMP-1 and -2).
      Immunochemical methods were utilized for quantification of the proteins in CSF
      and data analysis was performed with a multivariate discriminant algorithm. The
      concentrations of MBP, TIMP-1, P-tau(181), NF-L, T-tau, MMP-9, Abeta(1-42), and
      MMP-2 contributed the most to the separation between SVD and AD, with a
      sensitivity of 89% and a specificity of 90% (AUC = 0.92). MBP and NF-L performed
      the best in discriminating SVD from controls, while T-tau and Abeta(1-42)
      contributed the most in segregating AD from controls. The CSF biomarkers
      reflecting AD pathology (T-tau, P-tau(181), and Abeta(1-42)), white matter
      lesions (NF-L and MBP) and matrix remodeling (MMP-9 and TIMP-1) perform well in
      differentiating between SVD and AD patients.

PMID- 21860088
TI  - Folate/vitamin-B12 prevents chronic hyperhomocysteinemia-induced tau
      hyperphosphorylation and memory deficits in aged rats.
AB  - Hyperhomocysteinemia is associated with an increased risk of Alzheimer's disease
      (AD). Our previous work has demonstrated that combined folate and vitamin B12
      (vit-B12) supplementation prevents tau hyperphosphorylation and memory deficits
      induced by acute administration of homocysteine in young rats. Here, we further
      investigated whether folate/vit-B12 supplementation is also effective in aged
      rats with a chronically high level of homocysteine. 18-month-old rats were
      injected with homocysteine via the vena caudalis with or without a concurrent
      folate/vit-B12 supplementation for 28 weeks. We found that hyperhomocysteinemia
      induced tau hyperphosphorylation and accumulation in hippocampus and cortex.
      Concurrent signaling changes included the activation of glycogen synthase kinases
      3beta, cyclin-dependent kinase-5, c-Jun N-terminal kinase, extracellular signal
      regulated kinase, and p38MAPK, and inhibition of protein phosphatase 2A. Although
      the ability to learn was not affected, the aged rats exhibited significant memory
      deficits. Folate/vit-B12 supplementation attenuated these biochemical and
      behavioral correlates. These data demonstrate that folate/vit-B12 supplementation
      is also effective in a chronic hyperhomocysteinemia model in reversing the AD
      like tau pathologies and memory deficits.

PMID- 21860089
TI  - Wild type and Tangier disease ABCA1 mutants modulate cellular amyloid-beta
      production independent of cholesterol efflux activity.
AB  - Cerebral amyloid-beta (Abeta) deposition is a critical feature of Alzheimer's
      disease. Abeta is derived from the amyloid-beta protein precursor (AbetaPP) via
      two sequential cleavages that are mediated by beta-secretase and the gamma
      secretase complex. Such amyloidogenic AbetaPP processing occurs in lipid raft
      microdomains of cell membranes and it is thought that modulating the distribution
      of lipids in rafts may regulate AbetaPP processing and Abeta production. Certain
      ATP-binding cassette (ABC) transporters regulate lipid transport across cell
      membranes and, as recent studies reveal, within membrane microdomains. ABCA1 also
      regulates Abeta metabolism in the brain although its direct impact on AbetaPP
      remains an open question. Here we assessed the capacity of three ABCA1 mutants
      (that do not promote lipid efflux) to modulate AbetaPP processing. Unexpectedly,
      these non-functional mutants also reduced Abeta production similar to wild type
      ABCA1. ABCA1 expression did not alter AbetaPP localization in lipid rafts, and co
      immunoprecipitation experiments indicated ABCA1 and AbetaPP physically interact.
      These data suggest that ABCA1 may regulate AbetaPP processing independent of its
      impact on membrane lipid homeostasis.

PMID- 21860090
TI  - CRMP2 hyperphosphorylation is characteristic of Alzheimer's disease and not a
      feature common to other neurodegenerative diseases.
AB  - Collapsin response mediator protein 2 (CRMP2) is an abundant brain-enriched
      protein that regulates neurite outgrowth. It is phosphorylated by Cdk5 and GSK3,
      and these modifications are abnormally high in the brains of Alzheimer's disease
      (AD) patients. Increased phosphorylation of CRMP2 is also apparent in mouse
      models of AD that express mutated AbetaPP and PSEN1, but not AbetaPP or tau
      alone, where it is detectable before the appearance of amyloid plaques and
      neurofibrillary tangles, suggesting it is an early event in AD pathogenesis.
      Here, we have extended these observations by showing that CRMP2 is not
      hyperphosphorylated in mice overexpressing mutated PSEN1 alone, or in cultured
      neurons treated with soluble, oligomeric Abeta42 peptide. Similarly, CRMP2
      phosphorylation was not increased in a mouse model of severe neurodegeneration
      (PMSC-1 knockout) or in cultured neurons subjected to neurotoxic concentrations
      of NMDA or staurosporine. Most interestingly, CRMP2 phosphorylation was not
      increased in frontal cortex from patients with frontotemporal lobar degeneration
      associated with mutations in MAPT or with Pick bodies. Together, these
      observations are consistent with the hypothesis that abnormal phosphorylation of
      CRMP2 is specific to AD and occurs downstream of excessive processing of AbetaPP,
      but that neither excessive Abeta42 peptide nor neurotoxicity alone are sufficient
      to promote hyperphosphorylation.

PMID- 21860092
TI  - Memantine affects cognitive flexibility in the Morris water maze.
AB  - Alzheimer's disease (AD) is multi-factorial mental disorder characterized by a
      copious array of congruent features cumulating in disrupted memory and dysthymia.
      Though the mechanism remains elusive, the highly unspecific pharmaceutical,
      memantine, provides modest benefits for patients with moderate-to-severe AD. A
      greater understanding of how memantine affects cognitive function promises to
      facilitate the search for better therapeutics. We therefore examined cognitive
      flexibility of mice following 5 and 10 mg/kg memantine administration using a
      platform re-location water maze. Strikingly, subjects receiving memantine
      demonstrated memory impairment relative to controls when re-trained off drug,
      revealing a novel and unusual disruption of cognitive flexibility.

PMID- 21860091
TI  - Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone
      for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a major cause of dementia in the elderly with no
      effective treatment. Accumulation of amyloid-beta peptide (Abeta) in the brain,
      one of the pathological features of AD, is considered to be a central disease
      causing and disease-promoting event in AD. In this study, we showed that feeding
      male AbetaPP/PS1 transgenic mice, a well established mouse model of AD, with a
      diet containing phenolic antioxidant tert-butylhydroquinone (TBHQ) dramatically
      reduced brain Abeta load with no significant effect on the amounts of alpha- and
      beta-C-terminal fragments or full-length AbetaPP. Further studies showed that
      TBHQ diet inhibited the expression of plasminogen activator inhibitor-1 (PAI-1),
      a protease inhibitor which plays a critical role in brain Abeta accumulation in
      AD, accompanied by increases in the activities of tissue type and urokinase type
      plasminogen activators (tPA and uPA) as well as plasmin. Moreover, we showed that
      TBHQ diet increased the expression of low density lipoprotein related protein-1,
      a multi ligand endocytotic receptor involved in transporting Abeta out of the
      brain, and plasma Abeta(40) and Abeta(42) levels. We also showed that TBHQ diet
      increased the concentration of glutathione, an important antioxidant, and
      suppressed the expression of NADPH oxidase 2 as well as lipid peroxidation.
      Collectively, our data suggest that TBHQ may have therapeutic potential for AD by
      increasing brain antioxidant capacity/reducing oxidative stress level and by
      stimulating Abeta degradation/clearance pathways.

PMID- 21860093
TI  - Abeta1-16 can aggregate and induce the production of reactive oxygen species,
      nitric oxide, and inflammatory cytokines.
AB  - Amyloid-beta (Abeta40/42) aggregates containing the cross-beta-sheet structure
      are associated with the pathogenesis of Alzheimer's disease (AD). It is generally
      accepted that the N-terminal peptide of Abeta40/42, Abeta1-16, does not
      aggregate, and is not cytotoxic. However, we here show that Abeta1-16 can
      aggregate, and form cytotoxic aggregates containing beta-turns and regular non
      amyloid beta-sheet structures. Factors such as pH, ionic strength, and agitation
      were found to influence Abeta1-16 aggregation, and the amino acid residues Asp1,
      His6, Ser8, and Val12 in Abeta1-16 may play a role in this aggregation. Our MTT
      results showed that Abeta1-16 monomers or oligomers were toxic to SH-SY5Y cells,
      but Abeta1-16 fibrils exhibited less cytotoxicity. Our studies also indicate that
      Abeta1-16 aggregates can increase the formation of reactive oxygen species and
      nitric oxide, induce the loss of calcium homeostasis, and incur the microglial
      production of TNF-alpha and IL-4. Thus, our findings suggest that Abeta1-16 may
      contribute to AD pathogenesis.

PMID- 21860095
TI  - Cost of dementia in the pre-enlargement countries of the European Union.
AB  - Dementia has a significant impact on the health and social care systems of the
      European Union (EU), on patients, on family and friends who provide unpaid care,
      and on the wider economy and society. Information about its economic burden will
      be helpful when deciding the allocation of future research funds. We included the
      15 countries who were members of the EU (EU-15) before the Eastern enlargement in
      2004. The economic burden of dementia was estimated using patient-level studies
      and aggregate data on morbidity, mortality, and health and social care use. The
      same methodological approach was used across all countries. Healthcare and social
      care costs were estimated from expenditure on nursing and residential home care;
      and primary, outpatient, emergency and inpatient care, as well as drug treatment.
      Costs of unpaid care and lost earnings due to morbidity and premature death were
      also included in the study. Dementia was estimated to cost the EU-15 ${?rm
      ?euro}$189 billion in 2007. 68% of total costs were due to informal care, 26% to
      social care, 5% to health care and 1% to productivity losses. In conclusion,
      dementia poses a significant economic burden to European health and social care
      systems, and society overall. Our results will be helpful for policy makers in
      evaluating policy impact and prioritising research expenditures. This study also
      highlights the need for more accurate and comparable dementia-related data across
      the European countries.

PMID- 21860094
TI  - Task deactivation reductions and atrophy within parietal default mode regions are
      overlapping but only weakly correlated in mild cognitive impairment.
AB  - Reduced task deactivation within regions of the default mode network (DMN) has
      been frequently reported in Alzheimer's disease (AD) and amnestic mild cognitive
      impairment (aMCI). As task deactivation reductions become increasingly used in
      the study of early AD states, it is important to understand their relationship to
      atrophy. To address this issue, the present study compared task deactivation
      reductions during a lexical decision task and atrophy in aMCI, using a series of
      parallel voxel-wise and region-wise analyses of fMRI and structural data. Our
      results identified multiple regions within parietal cortex as convergence areas
      of task deactivation and atrophy in aMCI. Relationships between parietal regions
      showing overlapping task deactivation reductions and atrophy in aMCI were then
      explored. Regression analyses demonstrated minimal correlation between task
      deactivation reductions and either local or global atrophy in aMCI. In addition,
      a logistic regression model which combined task deactivation reductions and
      atrophy in parietal DMN regions showed higher classificatory accuracy of aMCI
      than separate task deactivation or atrophy models. Results suggest that task
      deactivation reductions and atrophy in parietal regions provide complementary
      rather than redundant information in aMCI. Future longitudinal studies will be
      required to assess the utility of combining task deactivation reductions and
      atrophy in the detection of early AD.

PMID- 21860096
TI  - Antimicrobial resistance: action by laboratories today for a cure tomorrow.

PMID- 21860097
TI  - Antimicrobial resistance and extinction.

PMID- 21860098
TI  - Towards a rational antimicrobial testing policy in the laboratory.
AB  - Antimicrobial policy for prophylactic and therapeutic use of antimicrobials in a
      tertiary care setting has gained importance. A hospital's antimicrobial policy as
      laid down by its hospital infection control team needs to include inputs from the
      microbiology laboratory, besides the pharmacy and therapeutic committee.
      Therefore, it is of utmost importance that clinical microbiologists across India
      follow international guidelines and also take into account local settings,
      especially detection and presence of resistance enzymes. This article draws a
      framework for rational antimicrobial testing in our laboratories in tertiary care
      centers, from the Clinical and Laboratory Standards Institute guidelines. It does
      not address testing methodologies but suggests ways and means by which
      antimicrobial susceptibility reporting can be rendered meaningful not only to the
      treating physician but also to the resistance monitoring epidemiologist. It hopes
      to initiate some standardization in rational choice of antimicrobial testing in
      laboratories in the country pertaining to nonfastidious bacteria.

PMID- 21860099
TI  - Is screening patients for antibiotic-resistant bacteria justified in the Indian
      context?
AB  - Infection with multi-antibiotic-resistant bacteria is a common clinical problem
      in India. In some countries and centres, screening patients to detect
      colonisation by these organisms is used to determine specific interventions such
      as decolonisation treatment, prophylactic antibiotics prior to surgical
      interventions or for selection of empirical antibiotic therapy, and to isolate
      patients so that transmission of these difficult to treat organisms to other
      patients could be prevented. In India, there is no national guideline or
      recommendation for screening patients for multi-drug-resistant (MDR) bacteria
      such as MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin
      resistant enterococcus), ESBL (extended spectrum beta-lactamase) or MBL (metallo
      beta-lactamase) producers. The present article discusses the relevance of
      screening patients for multi-antibiotic-resistant bacteria in the Indian context.
      Literature has been reviewed about antibiotic resistance in India, screening
      methodology, economic debate about screening. The percentages of strains from
      various hospitals in India which were reported to be MRSA was between 8 and 71%,
      those for ESBL between 19 and 60% and carbapenem-resistant Gram-negative bacilli
      between 5.3 and 59%. There exists culture-based technology for the detection of
      these resistant organisms from patient samples. For some pathogens, such as MRSA
      and VRE Polymerase chain reaction-based tests are also becoming available.
      Screening for MDR bacteria is an option which may be used after appraisal of the
      resources available, and after exploring possibility of implementing the
      interventions that may be required after a positive screening test result.

PMID- 21860100
TI  - Antibiotic resistance in ocular bacterial pathogens.
AB  - Bacterial infections of the eye are common and ophthalmologists are spoilt for
      choice with a variety of antibiotics available in the market. Antibiotics can be
      administered in the eye by a number of routes; topical, subconjunctival, subtenon
      and intraocular. Apart from a gamut of eye drops available, ophthalmologists also
      have the option of preparing fortified eye drops from parenteral formulations,
      thereby, achieving high concentrations; often much above the minimum inhibitory
      concentration (MIC), of antibiotics in ocular tissues during therapy. Antibiotic
      resistance among ocular pathogens is increasing in parallel with the increase
      seen over the years in bacteria associated with systemic infections. Although it
      is believed that the rise in resistant ocular bacterial isolates is linked to the
      rise in resistant systemic pathogens, recent evidence has correlated the
      emergence of resistant bacteria in the eye to prior topical antibiotic therapy.
      One would like to believe that either of these contributes to the emergence of
      resistance to antibiotics among ocular pathogens. Until recently, ocular
      pathogens resistant to fluoroquinolones have been minimal but the pattern is
      currently alarming. The new 8-fluoroquinolone on the scene-besifloxacin, is
      developed exclusively for ophthalmic use and it is hoped that it will escape the
      selective pressure for resistance because of lack of systemic use. In addition to
      development of new antibacterial agents, the strategies to halt or control
      further development of resistant ocular pathogens should always include judicious
      use of antibiotics in the treatment of human, animal or plant diseases.

PMID- 21860101
TI  - Antimicrobial resistance in typhoidal salmonellae.
AB  - Infections with Salmonella are an important public health problem worldwide. On a
      global scale, it has been appraised that Salmonella is responsible for an
      estimated 3 billion human infections each year. The World Health Organization
      (WHO) has estimated that annually typhoid fever accounts for 21.7 million
      illnesses (217,000 deaths) and paratyphoid fever accounts for 5.4 million of
      these cases. Infants, children, and adolescents in south-central and South
      eastern Asia experience the greatest burden of illness. In cases of enteric
      fever, including infections with S. Typhi and S. Paratyphi A and B, it is often
      necessary to commence treatment before the results of laboratory sensitivity
      tests are available. Hence, it is important to be aware of options and possible
      problems before beginning treatment. Ciprofloxacin has become the first-line drug
      of choice since the widespread emergence and spread of strains resistant to
      chloramphenicol, ampicillin, and trimethoprim. There is increase in the
      occurrence of strains resistant to ciprofloxacin. Reports of typhoidal
      salmonellae with increasing minimum inhibitory concentration (MIC) and resistance
      to newer quinolones raise the fear of potential treatment failures and
      necessitate the need for new, alternative antimicrobials. Extended-spectrum
      cephalosporins and azithromycin are the options available for the treatment of
      enteric fever. The emergence of broad spectrum beta-lactamases in typhoidal
      salmonellae constitutes a new challenge. Already there are rare reports of
      azithromycin resistance in typhoidal salmonellae leading to treatment failure.
      This review is based on published research from our centre and literature from
      elsewhere in the world. This brief review tries to summarize the history and
      recent trends in antimicrobial resistance in typhoidal salmonellae.

PMID- 21860102
TI  - Polymyxins: Antimicrobial susceptibility concerns and therapeutic options.
AB  - The increasing prevalence of multidrug-resistant nosocomial pathogens such as
      Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae poses a
      great challenge to the treating physicians. The paucity of newer effective
      antimicrobials has led to renewed interest in the polymyxin group of drugs, as a
      last resort for treatment of gram-negative bacterial infections. There is a
      dearth of information on the pharmacological properties of colistin, leading to
      difficulties in selecting the right dose, dosing interval, and route of
      administration for treatment, especially in critically-ill patients. The
      increasing use of colistin over the last few years necessitates the need for
      accurate and reliable in vitro susceptibility testing methods. Development of
      heteroresistant strains as a result of colistin monotherapy is also a growing
      concern. There is a compelling need from the clinicians to provide options for
      probable and possible colistin combination therapy for multidrug-resistant
      bacterial infections in the ICU setting. Newer combination drug synergy
      determination tests are being developed and reported. There are no standardized
      recommendations from antimicrobial susceptibility testing reference agencies for
      the testing and interpretation of these drug combinations. Comparison and
      analysis of these reported methodologies may help to understand and assist the
      microbiologist to choose the best method that produces accurate results at the
      earliest. This will help clinicians to select the appropriate combination
      therapy. In this era of multidrug resistance it is important for the microbiology
      laboratory to be prepared, by default, to provide timely synergistic
      susceptibility results in addition to routine susceptibility, if warranted. Not
      as a favour or at request, but as a responsibility.

PMID- 21860103
TI  - Drug resistance in malaria.
AB  - Antimalarial chemotherapy is an important component of all malaria control
      programmes throughout the world. This is especially so in light of the fact that
      there are no antimalarial vaccines which are available for clinical use at
      present. Emergence and spread of malaria parasites which are resistant to many of
      the available antimalarials today is, therefore, a major cause for concern. Till
      date, resistance to all groups of antimalarials excluding artemisinin has been
      reported. In recent years, in vitro resistance to even artemisinin has been
      described. While resistance to antibacterial agents has come to prominence as a
      clinical problem in recent years, antiparasitic resistance in general and
      antimalarial resistance in particular has not received much attention, especially
      in the Indian scenario. The present review deals with commonly used antimalarial
      drugs and the mechanisms of resistance to them. Various methods of detecting
      antimalarial resistance and avoiding the same have also been dealt with. Newer
      parasite targets which can be used in developing newer antimalarial agents and
      antimalarials obtained from plants have also been mentioned.

PMID- 21860104
TI  - Development of TaqMan real-time polymerase chain reaction for the detection of
      the newly emerging form of carbapenem resistance gene in clinical isolates of
      Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii.
AB  - PURPOSE: The newly emerging form of the so-called New Delhi Metallo-beta
      lactamases (NDM-1) has been reported recently from patients worldwide and broadly
      thought as a potential source for the major global health problem. Thus, it is
      important to study the epidemiology of the so-called NDM-1 harbouring bacteria to
      prevent its further spread and to place effective control measures. The present
      study describes the use of the real-time polymerase chain reaction (PCR) assay
      for the detection of the bla NDM-1 gene using TaqMan probes among clinical
      isolates. MATERIALS AND METHODS: Clinical isolates of Escherichia coli (11
      strains), Klebsiella pneumoniae (17 strains) and Acinetobacter baumannii (six
      strains) that were resistant to either of the carbapenems (meropenem or imipenem)
      were included in the study. The presence of carbapenemases in such strains was
      confirmed using the modified Hodge test. A real-time PCR assay was optimized for
      the detection of NDM-1 using a cloned synthetic gene fragment followed by testing
      of the clinical isolates. The findings were further confirmed using PCR and gene
      sequencing. RESULTS: TaqMan probe assay displayed a good detection limit with
      analytical sensitivity of the assay up to 10 copies of bla NDM-1 gene per
      reaction. The isolates of E. coli and K. pneumoniae revealed narrow range
      crossing point values (Cp values) between (12-17) cycles (mean Cp value 14),
      indicating number of bla NDM-1 gene copies of 106-108. The wider range of Cp
      values (15-34) cycles with a higher mean Cp value (23.6) was observed in A.
      baumannii with number of bla NDM-1 gene copies of 103-108. CONCLUSIONS: The study
      demonstrates that real-time PCR assay based on TaqMan chemistry is a useful
      technique for the detection of bla NDM-1 harbouring clinical isolates of E. coli,
      K. pneumoniae and A. baumannii. The assay has great precision in measuring the
      number of bla NDM-1 gene copies per specimen of DNA.

PMID- 21860105
TI  - Molecular characterization of CTX-Mbeta-lactamases among Klebsiella pneumoniae
      isolated from patients at Tehran hospitals.
AB  - PURPOSE: Plasmid-encoded CTX-M-group of extended-spectrum beta-lactamases (ESBLs)
      represent a significant and rapidly emerging problem in most part of the world.
      The aim of the present study was to describe the prevalence of CTX-M producing
      Klebsiella pneumoniae at Tehran hospitals. MATERIALS AND METHODS: Clinical
      isolates of K. pneumoniae (n=250) were collected from 10 hospitals of Tehran.
      Susceptibility to antimicrobial agents, MIC of cefotaxime and ESBLs production of
      collected isolates were detected. All ESBL-producing isolates were screened for
      bla CTX-M genes using PCR and DNA sequencing. Molecular typing of bla(CTX-M)
      harboring isolates was performed by Pulsed-field gel electrophoresis assay.
      RESULTS: Of 250 K. pneumoniae clinical isolates, 102 isolates revealed ESBLs -
      phenotype. PCR assay and sequencing detected bla(CTX-M) genes in 71.5% (n= 73) of
      ESBL-producing isolates. The prevalence of CTX-M -I and CTX-M-III clusters among
      these isolates was 35.61% (n=26) and 21.9 % (n=16) respectively. Coexistence of
      CTX-M -I and CTX-M-III clusters was found among 42.5% (n= 31) of isolates. Of 102
      isolates that were positive in the phenotypic confirmatory test (PCT), 29
      isolates (28.4%) did not produce any amplicons in PCR for bla(CTX-M) gene. The
      results of PCR for CTX-M -II and CTX-M-IV clusters were also negative. Analysis
      of the 31 CTX-M producing K. pneumoniae isolates by PFGE typing showed 26
      distinct patterns. CONCLUSIONS: The bla CTX-M genes are widespread among Iranian
      isolates of K. pneumoniae. PFGE demonstrated the high diversity of K. pneumoniae
      harboring bla(CTX-M) in our study.

PMID- 21860106
TI  - First detection of TEM-116 extended-spectrum beta-lactamase in a Providencia
      stuartii isolate from a Tunisian hospital.
AB  - PURPOSE: To study the resistance to third-generation cephalosporins in
      Providencia stuartii strain isolated from hospitalized patient in Tunisia and to
      identify the responsible genes MATERIALS AND METHODS: This strain was analysed by
      PCR and sequencing to identify the genes responsible for the beta-lactamase
      resistance phenotypes. The transferability of the phenotypes was tested by
      conjugation to Escherichia coli J53. The isoelectric point was determinate by
      isoelectrofocalisation. RESULTS: This resistance was carried by a 60 kb plasmid
      that encoded a beta-lactamase with a pI of 5.4. This beta-lactamase revealed
      identity with the blaTEM-1 gene encoding the TEM-1 beta-lactamase, except for a
      replacement of the Val residue at position 84 by Ile, and the Ala residue at
      position 184 by Val. These two mutations were encountered in TEM-116 beta
      lactamase. CONCLUSION: This study demonstrates the first description of TEM-116
      in the P. stuartii species in the world and the first one in a Tunisian hospital.

PMID- 21860107
TI  - Identification of plasmid-mediated quinolone resistance genes qnrA1, qnrB1 and
      aac(6')-1b-cr in a multiple drug-resistant isolate of Klebsiella pneumoniae from
      Chennai.
AB  - PURPOSE: Resistance to fluoroquinolones, a commonly prescribed antimicrobial for
      Gram-negative and Gram-positive microorganisms, is of importance in therapy. The
      purpose of this study was to screen for the presence of Plasmid-Mediated
      Quinolone Resistance (PMQR) determinants in clinical isolates of Klebsiella
      pneumoniae. MATERIALS AND METHODS: Extended-Spectrum Beta-Lactamase (ESBL)
      isolates of K. pneumoniae collected during October 2009 were screened by the
      antimicrobial susceptibility test. The plasmids from these isolates were analysed
      by specific Polymerase chain Reaction (PCR) for qnrA, qnrB and aac(6')-1b. The
      amplified products were sequenced to confirm the allele. RESULTS: Our analysis
      showed that 61% out of the 23 ESBL K. pneumoniae isolates were resistant to
      ciprofloxacin and 56% to levofloxacin. The PMQR was demonstrated by transforming
      the plasmids from two isolates P12 and P13 into E. coli JM109. The PMQR gene qnrA
      was found in 16 isolates and qnrB in 11 isolates. The plasmid pKNMGR13 which
      conferred an minimum inhibitory concentration (MIC) of more than 240 MUg/ml in
      sensitive E. coli was found to harbour the qnrA1 and qnrB1 allele. Furthermore,
      the gene aac(6')-1b-cr encoding a variant aminoglycoside 6'-N Acetyl transferase
      which confers resistance to fluoroquinolones was found in the same plasmid.
      CONCLUSIONS: Our report shows the prevalence of PMQR mediated by qnrA and qnrB in
      multidrug-resistant K. pneumoniae isolates from Chennai. A multidrug-resistant
      plasmid conferring high resistance to ciprofloxacin was found to harbour another
      PMQR gene, aac(6')-1b-cr mutant gene. This is the first report screening for PMQR
      in K. pneumoniae isolates from India.

PMID- 21860108
TI  - OXA beta-lactamase-mediated carbapenem resistance in Acinetobacter baumannii.
AB  - OBJECTIVES: Acinetobacter baumannii is a significant pathogen in health care
      settings. In recent years, an increase in carbapenem resistance among A.
      baumannii due to Ambler class B metallo-beta-lactamases or class D OXA
      carbapenamases has been reported. In this study we detected the presence of OXA
      carbapenamases and coproduction of metallo-beta-lactamases (blaVIM and blaIMP )
      by phenotypic and genotypic methods in carbapenem resistant clinical isolates of
      Acinetobacter baumannii. MATERIALS AND METHODS: A total of 116 consecutive, non
      duplicate carbapenem resistant A. baumannii isolated from various clinical
      specimens were included in the study. The modified Hodge test and inhibitor
      potentiated disk diffusion tests were done for the screening of carbapenamase and
      metallo-beta-lactamase production, respectively. Polymerase chain reaction (PCR)
      was performed for the detection of OXA (blaOXA 23 like, blaOXA 24 like, blaOXA-51
      like and blaOXA-58 like genes) and metallo-beta-lactamases (blaVIM and blaIMP )
      genes. Gene sequencing was performed for representative isolates. RESULTS: Among
      116 A. baumannii, OXA genes were detected in 106 isolates. BlaOXA 51 like (n =
      99) and blaOXA -23 like (n = 95) were the most common and they coexisted in 89
      isolates. blaOXA-24 like gene was detected in two isolates of which one also
      carried blaOXA-51 like and blaOXA-58 like genes. The modified Hodge test was
      positive in 113 isolates. The metallo-beta-lactamase screening test was positive
      in 92 isolates. blavim was detected in 54 isolates of which 1 also carried the
      blaIMP gene. CONCLUSIONS: blaOXA-23 like and bla OXA 51 like genes are the most
      common types of OXA carbapenamases while the blaVIM type is the most common type
      of metallo-beta-lactamase contributing to carbapenem resistance in clinical
      isolates of A. baumannii. The coproduction of OXA and metallo-beta-lactamases is
      not an uncommon phenomenon in A. baumannii.

PMID- 21860109
TI  - Zinc-dependent carbapenemases in clinical isolates of family Enterobacteriaceae.
AB  - PURPOSE: The emergence and spread of zinc-dependent carbapenem resistance has
      become a diagnostic challenge for clinical microbiologists. The objective of the
      present study was to screen zinc-dependent carbapenemase activity in clinical
      isolates of family Enterobacteriaceae. MATERIALS AND METHODS: A total of 102
      multidrug-resistant organisms (MDROs), non-repeat clinical isolates of family
      Enterobacteriaceae from two tertiary care centres in Delhi, were screened for
      carbapenemase production by a modified Hodge test (MHT) and additionally by a re
      modified Hodge test, EDTA double disc synergy test, and combined disc test (or
      disc enhancement test) to determine zinc dependence of carbapenemases harbouring
      bacteria. RESULTS: Of the total 102 clinical isolates (June through November
      2010), 91 were from urine and 11 were from blood specimens. The isolates were
      obtained from patients visiting the outpatient department (18 isolates), admitted
      in non-ICU inpatient care units (74 isolates) and patients admitted in ICUs (4
      isolates). MHT identified 92 (90.2%) isolates as carbapenemases producers. Among
      those found negative for MHT (n=10), metallo-beta-lactamases (MBLs) activity was
      demonstrated through the EDTA disc diffusion synergy test and the combined disc
      test in 8 and 9 isolates respectively. A total of 63 (61.7%) isolates
      demonstrated MBL activity despite in vitro sensitivity to Imipenem. CONCLUSIONS:
      The study demonstrated that supplementing the MHT with at least one of the
      screening methods increases the likelihood of picking up such isolates that may
      be missed by the MHT. The study also demonstrates the wide-spread presence of
      MBLs in Enterobacteriaceae members from patients visiting hospitals in east
      Delhi.

PMID- 21860110
TI  - Assessment of trends of ofloxacin resistance in Mycobacterium tuberculosis.
AB  - PURPOSE: Ofloxacin (OFX) is one of the potent fluoroquinolone (FQ) recommended to
      treat MDR-TB. Over a decade, the preexposure of this drug for the treatment of
      other bacterial infections has resulted in acquisition of FQ resistance among
      Mycobacterium tuberculosis strains. Considering this possibility, a study was
      undertaken in a tertiary care center in the capital city (India) to assess the
      drug resistance trends of OFX among susceptible and multidrug resistant (MDR)
      strains of M. tuberculosis. MATERIALS AND METHODS: A total of 102 M. tuberculosis
      isolates (47 susceptible to first-line drugs and 55 MDR isolates) were screened
      for susceptibility testing of OFX with a critical concentration of 2 MUg/ml by
      Lowenstein Jensen (LJ) proportion method. RESULTS: The results showed 40 (85.1%)
      isolates among 47 susceptible isolates and 34 (61.8%) isolates among 55 MDR
      isolates, were found to be susceptible to OFX. Fisher's exact test showed
      significant P-value (0.0136) demonstrating 1.377 fold (95% confidence interval)
      increased risk to become resistant to OFX than susceptible isolates. These
      finding shows decreased OFX susceptibility is not only limited to MDR isolates
      but also increasingly seen in susceptible strains as a result of drug abuse.
      CONCLUSIONS: Our finding were not alarming, but highlights the general risk of
      acquiring resistance to OFX, jeopardizing the potential for these drugs to be
      used as second-line anti-TB agents in the management of drug-resistant TB and
      creating incurable TB strains .

PMID- 21860111
TI  - Direct inoculation on Phoenix panels for identification and antimicrobial
      susceptibility from positive BACTEC cultures: first study from India.
AB  - PURPOSE: This was a prospective study planned in a super-specialty hospital in
      Delhi to reduce turnaround times of identification-susceptibility results of
      positive blood cultures. MATERIALS AND METHODS: One hundred consecutive single
      morphology non-duplicate cultures were inoculated on Becton Dickinson PhoenixTM
      panels by growth recovered directly from liquid BACTECTM media and after pure
      growth on solid media. RESULTS: Complete concordance was observed in 72.4% of
      gram-negative and 45.8% of gram-positive isolates. For gram-negative isolates,
      categorical agreement (CA) was >83% and essential agreement (EA) was >96% among
      all antibiotics tested, very major errors (VME) were 0.13%, major errors (ME)
      0.54%, and minor errors (MiE) were 3.01%. For gram-positive isolates, VME was
      0.73%, 1.10% MiE and no ME. It was observed that average time from receipt of
      specimen to release of reports was 30:34 h and 32 h for gram-negative and gram
      positive isolates if reports of "Direct" panels were to be released. CONCLUSIONS:
      By direct panel inoculation, a decrease of at least 18-20 h in turnaround time
      was observed compared with the standard method. This helps early change to
      effective antibiotic therapy and also reduces the expenditure incurred for a
      patient's hospital stay by average Rs 20,000 ($443) per day.

PMID- 21860112
TI  - Investigation of Ureaplasma urealyticum biovars and their relationship with
      antimicrobial resistance.
AB  - PURPOSE: To develop Taqman fluorescence quantitative polymerase chain reaction
      (PCR) method for investigating the characteristics of the distributions of
      Ureaplasma urealyticum (UU) biovars and to explore the relationship between UU
      biovars and antimicrobial resistance. MATERIALS AND METHODS: By the method of
      culture, Ureaplasma species were detected. Taqman fluorescence quantitative PCR
      for detecting UU biovars were developed and UU clinical isolates were detected to
      distinguish biovars. The broth micro-dilution susceptibility testing methods were
      used to determine UU susceptibility. RESULTS: By Taqman PCR method, UU biovars
      was successfully detected. Of 126 samples, biovar 1 was found in 73 (57.94%).
      There was a statistical difference between genital-urinary tract infection group
      and asymptomatic group (P<0.05). In the region, UU biovar 1 to 9 kinds of agents
      kept higher susceptibility rates, but biovar 2 maintained higher susceptibility
      rates only to tetracyclines. Compared with biovar 1, UU biovar 2 resistance rates
      to 7 kinds of agents were higher (P<0.05). CONCLUSIONS: (1) Our new established
      Taqman PCR method is a useful tool for screening UU biovars. (2) UU biovar 1
      predominated in asymptomatic population; whereas in genital-urinary tract
      infection population UU biovar 2 had a higher proportion. (3) The characteristics
      of drug resistance were different between UU biovars. Overall, both two biovars
      remained higher susceptibility rates to tetracyclines. A majority of biovor 1
      strains were sensitive to macrolides and quinolones; while only a small number of
      biovar 2 strains kept sensitive to roxithromycin and quinolones, a large
      proportion of biovar 2 strains were found in intermediate ranges.

PMID- 21860113
TI  - Comparison between the two-step and the three-step algorithms for the detection
      of toxigenic Clostridium difficile.
AB  - PURPOSE: To evaluate usefulness of applying either the two-step algorithm (Ag
      EIAs and CCNA) or the three-step algorithm (all three assays) for better
      confirmation of toxigenic Clostridium difficile. The antigen enzyme immunoassays
      (Ag-EIAs) can accurately identify the glutamate dehydrogenase antigen of
      toxigenic and nontoxigenic Clostridium difficile. Therefore, it is used in
      combination with a toxin-detecting assay [cell line culture neutralization assay
      (CCNA), or the enzyme immunoassays for toxins A and B (TOX-A/BII EIA)] to provide
      specific evidence of Clostridium difficile-associated diarrhoea. MATERIALS AND
      METHODS: A total of 151 nonformed stool specimens were tested by Ag-EIAs, TOX
      A/BII EIA, and CCNA. All tests were performed according to the manufacturer's
      instructions and the results of Ag-EIAs and TOX-A/BII EIA were read using a
      spectrophotometer at a wavelength of 450 nm. RESULTS: A total of 61 (40.7%), 38
      (25.3%), and 52 (34.7%) specimens tested positive with Ag-EIA, TOX-A/BII EIA, and
      CCNA, respectively. Overall, the sensitivity, specificity, negative predictive
      value, and positive predictive value for Ag-EIA were 94%, 87%, 96.6%, and 80.3%,
      respectively. Whereas for TOX-A/BII EIA, the sensitivity, specificity, negative
      predictive value, and positive predictive value were 73.1%, 100%, 87.5%, and
      100%, respectively. With the two-step algorithm, all 61 Ag-EIAs-positive cases
      required 2 days for confirmation. With the three-step algorithm, 37 (60.7%) cases
      were reported immediately, and the remaining 24 (39.3%) required further testing
      by CCNA. By applying the two-step algorithm, the workload and cost could be
      reduced by 28.2% compared with the three-step algorithm. CONCLUSIONS: The two
      step algorithm is the most practical for accurately detecting toxigenic
      Clostridium difficile, but it is time-consuming.

PMID- 21860115
TI  - Metallo beta lactamase producing Pseudomonas aeruginosa and Acinetobacter
      baumannii.
AB  - This study aims in identifying MBLs particularly Zn requiring Molecular Class B
      enzymes produced by Pseudomonas aeruginosa and Acinetobacter baumannii .The
      resistance by these organisms are in a rise against all antibiotics including
      carbapenems and no prescribed CLSI guidelines is available for detecting them.
      Clinical isolates antibiotic susceptibility was determined by number of
      phenotypic tests by addition of 50mM of 10 MUl zinc as cofactor for metallo beta
      lactamase production along with 0.5M ETDA of 5 MUl (930 MUg per disk) plain
      disks. Increase in zone size of the meropenem -EDTA disk compared to the
      meropenem disk without EDTA was recorded positive. For Zn requiring MBLs zone
      towards both disks of EDTA and Zn along with meropenem is detected by DDST.

PMID- 21860114
TI  - Comparison of the boronic acid disk potentiation test and cefepime-clavulanic
      acid method for the detection of ESBL among AmpC-producing Enterobacteriaceae.
AB  - PURPOSE: Extended spectrum beta-lactamase (ESBL) and AmpC beta-lactamase are
      important mechanisms of betalactam resistance among Enterobacteriaceae . The ESBL
      confirmation test described by Clinical Laboratory Standards Institute (CLSI) is
      in routine use. This method fails to detect ESBL in the presence of AmpC.
      Therefore, we compared two different ESBL detection methods against the CLSI
      confirmatory test. MATERIALS AND METHODS: A total 200 consecutive clinical
      isolates of Enterobacteriaceae from various clinical samples were tested for ESBL
      production using (i) CLSI described phenotypic confirmatory test (PCT), (ii)
      boronic acid disk potentiation test and (iii) cefepime-CA disk potentiation
      method. AmpC confirmation was done by a modified three-dimensional test. RESULTS:
      Among total 200 Enterobacteriaceae isolates, 82 were only ESBL producers, 12 were
      only AmpC producers, 55 were combined ESBL and AmpC producers, 14 were inducible
      AmpC producers and 37 isolates did not harboured any enzymes. The CLSI described
      PCT detected ESBL-producing organisms correctly but failed to detect 36.3% of
      ESBLs among combined enzyme producers. The boronic acid disk potentiation test
      reliably detected all ESBL, AmpC, and combined enzyme producers correctly. The
      cefepime-CA method detected all ESBLs correctly but another method of AmpC
      detection has to be adopted. CONCLUSION: The use of boronic acid in disk
      diffusion testing along with the CLSI described PCT enhances ESBL detection in
      the presence of AmpC betalactamases.

PMID- 21860116
TI  - CTX-M-9 group extended-spectrum beta-lactamases in neonatal stool isolates:
      emergence in India.
AB  - The study reports for the first time the identification of CTX-M-14-like and CTX
      M-27-like extended-spectrum beta-lactamases (ESBLs) belonging to the CTX-M-9
      group in Klebsiella pneumoniae and Escherichia coli isolated from the neonatal
      stool in India. The plasmid carrying the blaCTX-M-9 group in both the isolates
      was transferable. Till date, no other CTX-M group, except the CTX-M-1 group, has
      been reported from India. A total of 77% of the neonates had ESBL-producing K.
      pneumoniae or E. coli in their stool, and blaCTX-M-15 was the predominant ESBL
      gene. Although the CTX-M-9 group was found in the stool and did not cause
      infection, the detection of the CTX-M-9 group might be a prelude to future
      infections.

PMID- 21860117
TI  - Species distribution and anti-fungal susceptibility of Candidaemia at a multi
      super-specialty center in Southern India.
AB  - Candidaemia is one of the leading causes of nosocomial bloodstream infections.
      There is a rise in the incidence of non-albicans candidaemia and emergence of
      anti-fungal resistance. We performed a retrospective laboratory-based study over
      a period of 2 years (January 2009 to December 2010) at our quaternary care multi
      super-specialty hospital in Southern India. There had been 68 Candida isolates
      detected from the bloodstream of 55 patients during the study period. Overall,
      74% of cases were due to non-albicans Candida. C. tropicalis was most commonly
      isolated (39.7%), followed by C. albicans (26.4%). All Candida isolates remain
      susceptible to voriconazole, whereas highest degree of resistance was observed
      for fluconazole.

PMID- 21860118
TI  - High oxacillin, vancomycin and fluoroquinolone resistance amongst biofilm forming
      Staphylococcus aureus isolates from ulcerative keratitis infections.

PMID- 21860119
TI  - Glycopeptides--important treatment option for methicillin-resistant
      Staphylococcus aureus.

PMID- 21860121
TI  - Newer beta-lactam and beta-lactamase inhibitor combinations available in India:
      consensus and controversies.

PMID- 21860120
TI  - Linezolid-resistant Staphylococcus spp. at a tertiary care hospital of Andhra
      Pradesh.

PMID- 21860122
TI  - Penicillin resistant Streptococcus pneumoniae in India: effects of new clinical
      laboratory standards institute breakpoint and implications.

PMID- 21860123
TI  - Antibiotic resistance and molecular subtypes of clinical methicillin-resistant
      Staphylococcus aureus in a teaching hospital.

PMID- 21860124
TI  - Delivery rate in Benin City, Nigeria: are there seasonal variations?
AB  - OBJECTIVE: To determine if there are monthly variations in the rate of deliveries
      in Benin City, Nigeria. MATERIALS AND METHODS: A retrospective descriptive study
      carried out in the three major obstetric centers in Benin City, Nigeria. We
      extracted the total number of deliveries from the hospitals' records for over a
      five-year period and analyzed the figures for monthly variation in delivery
      rates. This was repeated for a standardized 30-day month and the findings noted.
      RESULTS: There were 28,686 deliveries during the study period with an average
      monthly delivery of 2,390. The monthly distribution showed a sinusoidal pattern
      with peak delivery rates in April-May and October and lowest rates in July-August
      and December. The months of April, May, and October had delivery rates that were
      significantly higher than the monthly average delivery rate, while the converse
      was true for July, August, and December at the 99% confidence interval.
      CONCLUSIONS: There exists a significant monthly variation in delivery rates in
      Benin City. This finding will prove valuable in health system planning and in the
      interpretation of seasonal variations in other reproductive parameters.

PMID- 21860125
TI  - Behavioral problems of siblings of epileptic children in Enugu.
AB  - BACKGROUND AND OBJECTIVE: The existence of a psychosocial dysfunction in the
      siblings of children with chronic illness has been documented. There are very few
      reports on siblings of children with epilepsy. The aim of this study is to
      investigate to what extent the children's epilepsy has affected their healthy
      siblings in our own center. MATERIALS AND METHODS: Epileptic patients who
      consecutively referred to the Pediatric Neurology Clinic of the University of
      Nigeria Teaching Hospital, Enugu, from October 1999 to September 2000 were
      recruited. Demographic data were obtained, with a questionnaire administered to
      the parents. Information on the behavior of the school-age siblings and control
      was obtained by the class teachers using Rutter's behavior scale (B2) for
      children (Teacher's Scale). RESULTS: One hundred and fifty-six children with
      epilepsy, of age four to fifteen years, 124 males and 32 females, with a Male:
      Female ratio of 4: 1, were recruited; and 156 school-age siblings of the
      epileptic children (index children) and 156 controls were studied. Prevalence of
      behavioral problems was 38.5 and 15.4%, respectively, among the index and control
      children ( P < 0.001). There was no significant sex difference in the two groups.
      There was a significant difference in the distribution of the types of behavior
      problems between the index and controls ( P < 0.05). The duration of epilepsy did
      not affect the prevalence of behavior problems ( P < 0.05), but seizure control
      had a significant effect on the prevalence of behavior problems ( P < 0.001).
      CONCLUSIONS: Siblings of children with epilepsy have more behavioral disturbances
      than controls. A strong association was found between poor seizure control and
      the prevalence of behavioral problems.

PMID- 21860126
TI  - Bilateral tubal ligation in a rural hospital in the Niger Delta, Nigeria.
AB  - BACKGROUND AND OBJECTIVE: To document bilateral tubal ligation (BTL) rates and
      highlight the need to improve on the rates. MATERIALS AND METHODS: A
      retrospective review of BTLs done in a five-year period from January 2000 to
      December 2004 constituted the study group. RESULTS: There were a total of 103
      BTLs, 58 were Caesarean BTLs, six were cases of BTL with repair of uterine
      rupture and 39 had BTL from mini-laparotomy. There were 937 Caesarean sections
      and 2,356 deliveries during the study period. BTL therefore constituted 0.044% of
      the total deliveries. The majority (51.7%) were above 35 years of age and
      grandmultiparity constituted 60.4% of BTL cases. The majority was in the low
      social Class 4 and 5 (41.3%). Grandmultiparity was the most common indication
      (60.4%). Previous Caesarean sections were more in the highest social class with a
      mean of 2.9 +/- 1.21 while ruptured uterus had the lowest. Unbooked cases of BTL
      constituted 62.1% of BTL. CONCLUSIONS: Bilateral tubal ligation rate was low in
      this study with grandmultiparity being the commonest indication, the majority of
      patients were elderly parturient and largely unbooked. Social class was highest
      among those with previous Caesarean section.

PMID- 21860127
TI  - Seroprevalence survey of rubella infection in pregnancy at the University of
      Benin Teaching Hospital, Benin City, Nigeria.
AB  - OBJECTIVE: To determine the serosusceptibility of rubella infection in pregnancy
      and the feasibility of establishing an organized prevention program in a tertiary
      hospital in Nigeria. MATERIALS AND METHODS: This prospective, cross-sectional,
      laboratory-based study involved 300 consecutive pregnant women who gave informed
      consent and were screened for rubella immunoglobulins G (IgG) and M (IgM), using
      the ELISA-based quantitative assay at the University of Benin Teaching Hospital,
      Nigeria. Of the cohort, 30 women later withdrew. IgG seropositive samples were
      screened for IgM antibodies. RESULTS: The mean age and parity of the women were
      30.0 +/- 4.8 years, 95% CI 29.727-30.873 and 2.0 +/- 1.4; 95% CI 1.317-1.661,
      respectively. IgG seroprevalence was 53%, while 10.0% of all IgG seropositive
      women were IgM seropositive. Most infections were acquired before the age of 35.
      None of the women ever had previous rubella vaccination. Rubella vaccine is
      scarce in Nigeria. CONCLUSIONS: Prevalence of rubella seromarkers for previous
      and current infection is high. Facilities for routine diagnosis and vaccination
      are lacking. Initiation of organized screening and vaccination programs is
      limited by lack of vaccine. We recommend immunization of children and women of
      child-bearing age as a cost-effective public health intervention strategy for
      managing the sequelae of the congenital rubella syndrome.

PMID- 21860128
TI  - Surgical consideration for benign bone tumors.
AB  - BACKGROUND: The surgical management of symptomatic benign bone tumor has been
      described in various manners in medical literature. However, there are few
      published reports on the presentation and surgical management of benign bone
      tumors in black African patients. OBJECTIVES: To determine the pattern of
      presentation of benign bone tumors and evaluate the common indications for
      surgery in a Nigerian Orthopedic Center. MATERIALS AND METHODS: This is a
      prospective study of 67 patients, surgically treated for benign bone tumors, over
      a three-year period, at the National Orthopedic Hospital, Lagos, Nigeria.
      RESULTS: The common histological types include, osteochondroma, giant cell tumor,
      and the simple bone cyst. These tumors have varying anatomic locations, but are
      more commonly located around the knee joint. In this series, most of the patients
      have presented with an active or aggressive stage of the disease. The most common
      indication for surgery is painful swelling; other indications include a
      pathological fracture, restricted range of movement, and peripheral nerve
      compression. The surgical procedures performed are simple excision, curettage,
      and stabilization; and 1-stage and 2-stage wide resection with reconstruction.
      Patients with significant bone defects have autologous bone grafting or
      methylmethacrylate cement application. Further stabilization is achieved with
      intramedullary or compression plate and screw fixation. Amputation has only been
      necessary in one patient with a huge aneurysmal bone cyst. At the average follow
      up period of 28.6 months, five patients showed recurrence. All were with a
      histological diagnosis of giant cell tumor. CONCLUSIONS: The mode of presentation
      of benign bone tumors in this group of black African patients is heterogenous,
      demanding various surgical options. Limb sparing is a largely feasible option,
      but the recurrence rate is particularly higher for giant cell tumors. Increase in
      the number of patients presenting with giant cell tumors raises the possibility
      of an increase in the incidence of this condition in the black African
      population. Larger multicenter studies in the black African population may shed
      more light on the actual incidence of giant cell tumors and other bone tumors in
      this group of patients.

PMID- 21860129
TI  - Survey of urologists on clients' demand for screening for prostate cancer in
      Nigeria.
AB  - OBJECTIVE: The aim of this article is to document the experience of urologists on
      clients' demand for prostate cancer screening among Nigerians. MATERIALS AND
      METHODS: The study is a cross-sectional evaluation of the urologists that
      attended the Fourteenth Annual Meeting and the Scientific Conference of the
      Nigerian Association of Urological Surgeons. A structured questionnaire was used
      to assess the estimated workload of the respondents, with reference to prostate
      cancer management, the stage proportion at the time of diagnosis, and the
      proportion of patients requesting for CaP screening. The data was analyzed using
      the SPSS version 15 statistical software. RESULTS: Twenty-two respondents
      completed and returned the questionnaire and formed the basis of further
      analysis. About 76.9% of the consultant urologists were also lecturers in their
      respective universities. They were all actively practicing and a majority of
      them, 76.9%, had up to 10 years experience as practicing urologists. The majority
      of the respondents managed between one and fifteen new patients with CaP every
      month, with 36.4% of them managing more than 15 new patients on an average every
      month. About 95.4% of all the patients seen by the respondents were diagnosed
      with advanced stages of the disease, while the remaining ones were incidental
      findings. About one half of the respondents attended to clients seeking for
      advice on CaP 'often' or 'very often,' while 40.9% attended to them
      'occasionally,' with a mean of 4.67 clients seeking advice per month. The
      majority of respondents, 20 (22); 90.9%, were 'not aware' of any national
      guideline on CaP screening. CONCLUSIONS: A majority of practitioners affirmed
      that patients with prostate cancer present late. The mean number of patients
      requesting for screening for prostate cancer per month, per respondent, for CaP,
      is still low. It is the authors' belief that the trend may not change until there
      is an appropriate effort at health education, to enlighten the populace.

PMID- 21860130
TI  - Effect of hemodialysis on total antioxidant status of chronic renal failure
      patients in government hospitals in Lagos Nigeria.
AB  - BACKGROUND: Renal failure is accompanied by oxidative stress, which is caused by
      enhanced production of reactive oxygen species and impaired antioxidant defense.
      AIM: To assess the effect of hemodialysis (by cellulose membrane dialyzer) on
      plasma total antioxidant status and lipid peroxidation of patients in chronic
      renal failure before and after dialysis. OBJECTIVE: The finding would serve as
      guide to administration or otherwise of supplementary therapeutic antioxidant
      before or after hemodialysis. Also, it will assist in the choice of antioxidant
      impregnated over the conventional non-impregnated dialyzer membrane. MATERIALS
      AND METHODS: Twenty-five patients (14 men and 11 women, aged 24-75 years; median
      61) with end-stage renal failure who were undergoing hemodialysis for the first
      time were recruited. Plasma level of potassium (K+), sodium (Na+), blood urea
      nitrogen (BUN), creatinine, total antioxidant status (TAS), and lipid
      peroxidation (MDA) were measured, before and after hemodialysis. RESULTS: The
      mean +/- SD of plasma level of TAS (1.10 +/- 0.3 mmol/L trolox Eq) for males and
      (1.09 +/- 0.2 mmol/L trolox Eq) for females postdialysis were significantly
      reduced ( P < 0.05) in comparison with (1.72 +/- 0.4 mmol/L trolox Eq) for males
      and (1.83 +/- 0.7 mmol/L trolox Eq) for females predialysis, respectively.
      However, the mean +/- SD plasma level of MDA (6.03 +/- 0.4 nmol/ml) for males and
      (6.71 +/- 0.7 nmol/ml) for females were significantly increased postdialysis ( P
      < 0.01) compared to predialysis (3.98 +/- 0.8 nmol/ml) for males and (4.05 +/-
      0.9 nmol/ml) for females, respectively. CONCLUSIONS: Based on the outcome of this
      study, it is suggested that antioxidant-impregnated dialysis membranes and/or
      exogenous supplementary antioxidant would be beneficial to patients with chronic
      renal failure. Removal of reactive oxygen species could improve the health and
      general quality of life of uremic patients.

PMID- 21860131
TI  - Childhood suppurative otitis media in Abakaliki: isolated microbes and in vitro
      antibiotic sensitivity pattern.
AB  - BACKGROUND: Suppurative otitis media (SOM) is the most common pediatric problem
      seen by otolaryngologists in Nigeria. Devising simple and effective ways of
      treating pediatric patients with suppurating ears, especially in situations
      without a specialist care, will help prevent chronicity. Our experience with som
      at the ebonyi state university teaching hospital (ebsuth), abakaliki, is reviewed
      in this study. it may serve as a guide in patient care. OBJECTIVE: Determine the
      bacteriology of SOM in children in Abakaliki and ascertain their sensitivity to
      common antibiotics. MATERIALS AND METHODS: A 2-year retrospective analysis of ear
      swabs culture results and case files of children aged 0-18 years with SOM managed
      in EBSUTH. RESULTS: Sixty-five patients with discharging ears were reviewed. Of
      these, 73% were <= 5 years, of which 41.5% were infants. About 83% had unilateral
      ear discharge. Acute suppuration was seen in 67%. Overall swab yield was 87.7%;
      Pseudomonas was (57.4%), Klebsiella (16.4%), and Proteus species (11.5%).
      Ciprofloxacin showed 60% sensitivity, Gentamicin (58%), and Ceftazidime (35%).
      Amoxicillin/Clavulanic acid, ceftriaxone, and cefuroxime showed sensitivity of
      4.3%-9.7%. CONCLUSIONS: Treatment protocols of SOM in children should emphasize
      the use of Ciprofloxacin or Gentamicin, especially in situations with limited
      access to laboratory services or specialist care.

PMID- 21860132
TI  - Prevalence and correlates of aggression among psychiatric in-patients at Jos
      University Teaching Hospital.
AB  - OBJECTIVE: The study was designed to determine the prevalence of aggression and
      clinical factors associated with aggression among psychiatric in-patients at Jos
      University Teaching Hospital. This will help create a good knowledge base about
      management of these patients. MATERIALS AND METHODS: All admitted psychiatric
      patients between December, 2005, and February, 2007, that met the ICD-10 criteria
      for a specific clinical diagnosis were included. The modified overt aggression
      scale was subsequently used to assess the type and severity of aggression.
      Additional information was obtained through a self-designed questionnaire
      containing sociodemographic and psychiatric illness variables. RESULTS: A total
      of 300 subjects satisfied the inclusion criteria, but only 298 were assessed
      because two patients absconded from the wards during the study period. The
      prevalence of aggression in this study was 19.5%. Of the 58 aggressive patients,
      35 (21.7%) and 23 (16.8%) were male and female, respectively. Schizophrenic
      patients (31%) exhibited aggression more than any other diagnostic category. Most
      of the aggressive behavior occurred without provocation (63.3%). Aggression among
      psychiatric patients was associated with a history of previous acts of aggression
      and delusion of persecution. CONCLUSIONS: Aggression is a significant clinical
      problem in psychiatric facilities. Consequences of aggression among psychiatric
      patients can be far reaching for the mental health worker. More longitudinal
      studies should be carried out among specific diagnostic categories of psychiatric
      patients to determine factors associated with aggression in each.

PMID- 21860133
TI  - Hysterosalpingographic findings in infertile women: a seven year review.
AB  - OBJECTIVES: To review the hysterosalpingographic (HSG) findings in women
      investigated for infertility in a tertiary center in north eastern Nigeria.
      MATERIALS AND METHODS: A retrospective review of HSG films of 272 women
      investigated for infertility between January 2000 and December 2006 were
      reviewed. RESULTS: One hundred and thirty (47.8%) were investigated for primary
      infertility, while 142 (52.2%) were investigated for secondary infertility. Most
      of the women investigated for infertility by HSG had abnormal findings
      192(70.6%). The most common pathology revealed among the infertile women was
      tuboperitoneal factor in 196 (72.1%) followed by uterine synechia in 35(12.9%).
      Seventeen (6.3%) had bilateral tubal block and 5 (1.8%) had bicornuate uterus.
      CONCLUSION: HSG is helpful in the investigation of infertile women.

PMID- 21860134
TI  - Prevalence of dyslipidemia among adult diabetic patients with overt diabetic
      nephropathy in Anambra state south-east Nigeria.
AB  - BACKGROUND: Dyslipidemia has been identified as a risk factor for the development
      and progression of diabetic renal disease. OBJECTIVE: This study was done to
      determine the prevalence of dyslipidemia among diabetic patients with overt
      nephropathy. MATERIALS AND METHODS: A total of 72 diabetic patients with overt
      diabetic nephropathy and 36 age- and sex-matched normoalbuminuric diabetic
      patients were studied. Their fasting lipid profile, fasting blood sugar, and
      renal function tests were evaluated. RESULTS: Total serum cholesterol and serum
      triglycerides were significantly higher in patients with overt diabetic
      nephropathy compared to the controls; 66.7% and 62.5% versus 36.1% and 30.6%,
      respectively ( P = 0.003 and 0.002, respectively). CONCLUSIONS: Diabetic patients
      with overt diabetic nephropathy have significant dyslipidemia and aggressive
      lipid lowering in these patients may retard their progression to end-stage renal
      disease.

PMID- 21860135
TI  - Seroprevalence of Chlamydia trachomatis in Enugu, Nigeria.
AB  - BACKGROUND: Chlamydia infections in women cause pelvic inflammatory disease,
      which often results in devastating consequences of infertility, ectopic
      pregnancy, or chronic pelvic pain. The infection is largely asymptomatic.
      OBJECTIVE: To determine the seroprevalence of Chlamydia trachomatis in Enugu,
      South Eastern Nigeria. MATERIALS AND METHODS: A population-based prospective
      study comprising female residents of Enugu, South Eastern Nigeria. Indirect solid
      phase enzyme immunoassay of Chlamydia antibodies was done using ImmunoComb C0.
      Trachomatis IgG Kit (Orgenics). RESULTS: The population comprised 136 female
      undergraduate students and 150 non-student women. The overall prevalence of C.
      trachomatis in the population studied was 29.4%. The percentage of subjects who
      admitted to be having multiple sexual partners was higher among the student
      population (71.2%) compared to those from the non-student population (28.8%). The
      highest percentage of seroprevalence was 28 (33.3%) in the age group of 20-24
      years for the student population and 18 (21.4%) in the age group of 25-29 years
      for the non-student population. The highest seroprevalence of C. trachomatis
      antibodies (69.0%) in both populations was observed in females without any
      history of infection. Females that had pelvic inflammatory disease, sexually
      transmitted infection, and secondary infertility assayed for C. trachomatis had
      seroprevalence levels of 19%, 9.5%, and 2.4%, respectively. There was a positive
      correlation between positive Chlamydia assay and the type of subject population
      (student or non-student) with r2 value of 1.55 at P < 0.01. CONCLUSIONS: C.
      trachomatis infection is largely underdiagnosed and remains a silent disease in
      the apparently healthy population of Enugu, South eastern Nigeria.

PMID- 21860136
TI  - Chronic liver disease and hepatic encephalopathy: clinical profile and outcomes.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is an important neuropsychiatry
      complication of liver disease causing significant morbidity and mortality
      worldwide. Efforts at improving the outcome have resulted in development of new
      strategies in the management given the background of new insights in the
      pathogenesis of this disease entity. Understanding the disease profile including
      precipitants as well as prognostic factors will contribute in this regard as new
      strategies are yet to be widely applied. The aim of this report is to document
      the profile of patients with HE, the precipitants, prognostic factors as well as
      the scope of the burden associated with it. MATERIALS AND METHODS: In this
      prospective study, all patients managed for HE from January to December 2008 were
      recruited. A questionnaire was used to extract their basic demographics, clinical
      features noting any possible precipitants, complications, management protocol as
      well as outcome. RESULTS: A total of 21 subjects (11 females and 10 males) within
      the age range of 16-83 years were seen during the period under review. (mean age
      57.9 +/- 13). There was no significant difference in the mean ages of males and
      females. Two patients had acute encephalopathy, while others had acute-on chronic
      encephalopathy. The risk factors for liver disease included significant alcohol
      ingestion, hepatitis B virus infection, and previous jaundice, while other
      complications of liver disease noted were deepening jaundice, ascites, bleeding
      tendencies, and renal failure. The identified precipitants for HE were sepsis 6
      (29%), electrolyte inbalance 3 (14%), gastrointestinal bleed 5 (24%), drugs (5%),
      and possible malignant transformation 6 (29%). Focus of sepsis was bacterial
      peritonitis in two cases. Majority of our patients (61%) came during advanced
      stage of liver disease (Child-Pugh class C). Length of hospital stay ranged from
      1 to 7 weeks and a mortality of 48% was observed. Predictors of mortality were a
      history of significant alcohol ingestion, previous blood transfusion, Hepatitis B
      and C infections, and severe liver dysfunction on presentation (Child-Pugh class
      C). CONCLUSIONS: HE is associated with a high mortality rate and this scenario is
      associated with a history of previous blood transfusion, Hepatitis B and C
      infections, and severe liver dysfunction on presentation. Measures to reduce the
      burden of viral Hepatitis B and C, safe blood transfusion, and responsible use of
      alcohol should be promoted. Screening of those at risk of encephalopathy (liver
      disease patients) with a psychometric test of good predictability should be part
      of their routine evaluation in daily practice so as to detect cases of latent
      encephalopathy. Intensive care facilities and necessary personnel should be
      provided.

PMID- 21860137
TI  - Motorcycle injuries in North-Central Nigeria.
AB  - BACKGROUND: The increasing use of commercial motorcycle as mode of transportation
      in urban cities in Nigeria has become important source of morbidity and
      mortality. This is coupled with poor helmet use, narrow roads, increasing
      traffic, and poor licensing of the motorcycle riders. The objectives of this
      study are to determine the pattern of injuries following accident involving
      motorcycles, the mortality rate, and the immediate causes of mortality. MATERIALS
      AND METHODS: This is a combined retrospective and prospective study spanning over
      2 years (1 year each). Patient's records were retrieved to collate data for the
      retrospective study while all the patients presenting to the casualty unit of Jos
      University Teaching Hospital following involvement in motorcycle accidents
      between April 2006 and March 2007 were selected for the study. RESULTS: Out of
      485 motorcycle injured patients, 295 and 190 were recruited from the
      retrospective and prospective study respectively. The male: female (M: F) ratio
      was 4.8:1. The ages ranged from 2.5 to 84 years with a peak at 21-30 years. The
      total number of injuries was 559 with 443 patients singly injured and 42 patients
      multiply traumatized. Head injury (40.1%) was the most frequently occurring
      injury followed closely by extremity injuries (38.1%). None of the patients wore
      protective helmet. Thirty-six (36) mortalities (7.4%) were recorded and all dead
      patients had head injuries. All deaths occurred within 24 h. CONCLUSIONS: Head
      injury represents a common cause of morbidity and mortality following motorcycle
      injuries in our environment. Therefore, strict enforcement of helmet laws from
      May 10, 2010 may reduce morbidity and mortality.

PMID- 21860138
TI  - Non-consensual sex in Benin.
AB  - OBJECTIVE: The objective of the study is to investigate the prevalence and risk
      factors of non-consensual sex/rape in Benin. MATERIALS AND METHODS: We surveyed
      580 females in the University Community of Benin, 414 questionnaires were
      sufficiently completed for analysis. RESULTS: Seventy-six (18.4%) respondents
      reported that they had been victims of non-consensual sex (NCS), 36 in their
      current relationship. The unmarried single respondents had the lowest mean age at
      NCS experience of 18 years, while the divorced victims had the highest mean age
      of 32.5 ( P = 0.000). There was a major exposure peak age at 19 years with a
      smaller peak at 25. The majority of sex offenders were their present partners and
      next the husbands (22.2%). The father was the perpetrator on one (2.78%)
      occasion, while armed robbers raped two of the victims. Eighteen of the seventy
      six respondents made a formal report. Cumulatively, 95.4% of the respondents felt
      it was futile reporting, four (5.3%) felt it was not all a bad experience. The
      risk of being infected with the HIV/AIDS virus was the worst fear. Ninety-five of
      four hundred and fourteen respondents want the public and parents to be educated,
      64 would like the penal code to be tougher and better implemented, while 64
      (14.0%) crave for a dress code for the University community. CONCLUSIONS: The
      self-reported incidence of NCS is high, majority were not formally reported as
      most of the sex offenders were the (ex)partners of the victims. There was a major
      exposure peak age at 19 with a smaller peak at 25 years. There was a condoned
      sense of futility and frustration in reporting.

PMID- 21860139
TI  - Diagnosis of malaria parasitemia in children using a rapid diagnostic test.
AB  - AIM: This cross-sectional study was conducted to evaluate the diagnostic
      performance of a new rapid immunochromatographic test named "Paracheck pf" in the
      diagnosis of malaria in Nigerian children. MATERIALS AND METHODS: A total of 380
      Nigerian children aged between 6 and 59 months who presented at the University of
      Nigeria Teaching Hospital (UNTH) Enugu with fever and no obvious focus of any
      other infection were consecutively recruited. Malaria parasitemia was determined
      using simple microscopy and "Paracheck pf". RESULTS: "Paracheck pf" has the
      following diagnostic performance characteristics: Sensitivity of 82%, specificity
      of 91.5%, negative predictive value of 91.5%, positive predictive value of 82%, a
      strong positive correlation between parasite density and test sensitivity, and a
      detection limit of 397 parasites/MUl. CONCLUSIONS: The test is, therefore,
      recommended for the use in Nigerian children aged between 6 and 59 months in
      Enugu for the diagnosis of malaria, but negative results should be cautiously
      interpreted in infants because symptomatic malaria may occur in these children at
      parasite densities as low as 100/MUl.

PMID- 21860140
TI  - Prevalence and characteristics of cigarette smokers among undergraduates of the
      University of Ilorin, Nigeria.
AB  - BACKGROUND: Smoking control is urgently needed to prevent the epidemic of tobacco
      related diseases and deaths in developing countries. This requires data on
      smoking, especially among vulnerable groups like students. We have surveyed
      cigarette smoking among undergraduates of the University of Ilorin, in the North
      Central region of Nigeria. MATERIALS AND METHODS: This was a questionnaire-based
      survey among undergraduates of the University of Ilorin. A total of 1800 students
      were selected by multistage random sampling. RESULTS: A total of 1754 students
      (234 medical and 1520 non-medical students) completed the questionnaires. They
      were 1148 (65.5%) males and 606 (34.5%) females with a mean age of 21.6 +/- 3.1
      years. The prevalence rate of current smoking was 5.7% (males 7.7%, females 2.0%)
      and of ever smoking was 17.1% (males 22.9%, females 6.2%). Smoking was more
      common in non-medical students. Eighty-three (83.8%) of the smokers had already
      started smoking by their eighteenth birthday. Fifty-one (51.5%) of them smoked <=
      5 sticks of cigarettes daily. Most of them were influenced into smoking by peer
      pressure and commercial advertisements. Sixty-seven (67.6%) of them believed that
      smoking could never have a negative impact on their health status and quality of
      life and just 39 (39.4%) smokers were willing to quit. CONCLUSIONS: Despite the
      low prevalence rate of smoking in the studied population, a majority of them were
      not willing to quit because of a low perception of the negative effects of
      smoking on their health and quality of life. Comprehensive antismoking campaigns
      were urgently needed to control cigarette smoking among University undergraduates
      in Nigeria.

PMID- 21860141
TI  - Clinical correlate of tuberculosis in HIV co-infected children at the University
      of Abuja Teaching Hospital, Gwagwalada, Nigeria.
AB  - BACKGROUND: Tuberculosis (TB) co-infection with HIV is becoming a global
      emergency especially in the sub-Saharan Africa. Its diagnosis is notoriously
      challenging in countries with poor resource settings with limited diagnostic
      facilities. OBJECTIVE: To determine the prevalence, pattern, outcome, and
      clinical risk factors of TB in HIV co-infected children in Abuja, Nigeria.
      MATERIALS AND METHODS: An 18 months retrospective review of HIV-infected children
      diagnosed as having co-infection with TB was carried out at the special treatment
      clinic of the University of Abuja Teaching Hospital (UATH), Gwagwalada, from
      February 2007 to August 2008 for the above objectives. RESULTS: Of a total 210
      HIV-infected children observed during the review period, 41 (19.5%) were
      diagnosed as having co-existing TB. Their mean age, weight, CD4 cell count and
      its percentage were 6.3 +/- 2.4 years, 14.3 +/- 3.4 kg, 262 +/- 28.0 cells/ml,
      and 9.9%, respectively. Pulmonary TB accounted for 59% of all TB cases seen,
      while disseminated form was seen in 26.8%. Bone involvement was the least common
      form seen in only (2.4%) of cases. Confirmation of TB was only possible by
      positive smear and histology in 22.0% of cases, while 78.0% of cases remained
      unconfirmed. Co-infection was significantly higher in older children (>5 years)
      than in younger children <5 years (32 vs 9, P < 0.05). Severe weight loss was the
      only clinical feature found to have a fairly good sensitivity (88.9%) and
      specificity (88.6%) for TB in co-infected children, with a positive predictive
      value of 23.0%. While immune reconstitution syndrome (IRS) occurred in 2 (4.9%)
      of the patients, only one death (2.4%) was recorded among the co-infected
      children. CONCLUSIONS: TB co-infection with HIV in children is common in this
      environment. Severe weight loss can be used as a clinical guide to identify HIV
      infected children at risk of co-infection with TB who will require further
      evaluation.

PMID- 21860142
TI  - Obesity in adult Nigerians: a study of its pattern and common primary co
      morbidities in a rural Mission General Hospital in Imo state,South-Eastern
      Nigeria.
AB  - OBJECTIVES: This study was generally aimed at determining the prevalence and
      pattern of obesity using body mass index (BMI) criterion and specifically
      screening for its common primary co-morbidities among adult Nigerians attending a
      rural Mission General Hospital in Imo state, South-Eastern Nigeria. MATERIALS AND
      METHODS: A descriptive study was carried out from June 2008 to May 2009. A total
      of 2156 consecutive new adult patients aged 18-90 years were screened for obesity
      using the BMI criterion, and 129 patients had BMI >= 30 kg/m2 and met the
      inclusion criteria. The data collected included age, sex, marital status,
      education, occupation, social class, weight, height and blood pressure, fasting
      blood sugar and lipid profile. RESULTS: The prevalence of obesity was 6.0%, with
      class I obesity (86.1%) being the most common pattern. Hypertension (16.3%) was
      the most common primary co-morbidity; others included low high-density
      lipoprotein-cholesterol (21.7%), high low-density lipoprotein-cholesterol (9.3%),
      high total cholesterol (7.8%), high triglyceridemia (4.7%) and diabetes mellitus
      (3.9%). CONCLUSIONS: This study has shown that obesity and its primary co
      morbidities are emerging as a serious health problem among the study population,
      with class I obesity being the most common pattern and hypertension being the
      most common primary co-morbidity. Anthropometric determination of obesity and
      screening for its common primary co-morbidities should be integrated as part of
      the clinic baseline assessment of adult Nigerians attending rural hospitals to
      facilitate their early detection and institutionalization of appropriate
      preventive and therapeutic measures.

PMID- 21860143
TI  - Facet joints infiltration: a viable alternative treatment to physiotherapy in
      patients with low back pain due to facet joint arthropathy.
AB  - BACKGROUND: There is a paucity of information on treatment options and outcome of
      treatment of patients that have MRI findings of FJA presenting with low back pain
      in the developing country. This prospective cohort study conducted mainly in the
      University of Abuja Teaching Hospital Gwagwalada, Abuja Nigeria is to compare the
      short-term clinical outcome between two groups, one having undergone facet joints
      infiltration (FJI) and the other physiotherapy for facet joint arthropathy (FJA).
      MATERIALS AND METHODS: All patients with clinical lower back pain (LBP) and MRI
      features of FJA were recruited into this prospective study randomly. All the FJI
      patients had depot methylprednisolone and the physiotherapy patients had McKenzie
      regimen. Outcome questionnaires comprising Oswentry disability index scores
      (ODI), visual analogue scores (VAS), and patient satisfaction scores (PSS) were
      completed at all clinic visits. Follow-up was for 6 months for both groups. The
      results were analyzed using SPSS 17.0. RESULT: There were 10 FJI patients and 8
      physiotherapy patients (1.25: 1). The outcome scores comprised the following ODI,
      VAS, and PSS. The FJI group had a better score compared to the physiotherapy
      group at short-term evaluation and this difference was statistically significant.
      The female patients in both groups fare better compared to the male counterparts.
      CONCLUSIONS: FJI offered added benefit over physiotherapy in LBPs diagnosed with
      FJA. Patients with FJI have a significant reduction in pain symptom than the
      patients in the physiotherapy group. Though majority of the patients reported
      satisfactory outcome, the FJI patients group had a better outcome.

PMID- 21860144
TI  - Clinical pattern of gynecological/early pregnancy complaints and the outcome of
      pelvic sonography in a private diagnostic center in Ilorin.
AB  - BACKGROUND: Gynecological and early pregnancy complaints (GEPC)/lower abdominal
      complaints (LAC) are common in female patients seeking medical advice or
      treatments. Clinical limitations of GEPC or LAC are better resolved through
      appropriate laboratory and imaging investigation, among which the ultrasound
      examination (USS) is one. AIM: To determine the distribution/clinical pattern of
      female patients with GEPC/LAC, and to evaluate the correlation between the
      clinical and sonographical diagnoses, as seen in a private diagnostic center in
      the Ilorin metropolis. MATERIALS AND METHODS: Records of 253 consecutive cases
      with GEPC/LAC, who had USS, were retrieved using 3.5 and 5 MHZ probes with
      SIEMENS Sonoline SL-1 machine, from January 2004 to December 2006, and
      retrospectively analyzed for the following variables: Age, occupation, complaints
      of vaginal bleeding, with or without pain, history of amenorrhea or infertility,
      clinical and ultrasound impression of early pregnancy complaints, including
      ectopic pregnancies and pelvic inflammatory diseases (PID), with exclusion of
      urogenital and gastrointestinal complaints/cases. Pregnancies greater than 12
      weeks were excluded, bringing the total number of cases examined to 242. RESULTS:
      Mean age was 30.44 years, median = 29.00; Mode = 25.00; with an STD of 7.69973.
      The youngest patient was 15-years-old while the oldest was 70 years. Cases of
      bleeding per vaginam Bleeding per vaginam (BPV), with or without pain, were the
      highest, 149 cases (61.6%), followed by threatened abortion, 45 cases (18.6%),
      and non-viable or incomplete abortions, 13 cases (5.4%). In contrast
      dysfunctional uterine bleedings (DUB) ranked the highest among the USS results,
      with 62 cases (25.6%), incomplete abortion cases were 44 (18.2%), while the non
      viable pregnancies (missed abortions, blighted ovum, and early intrauterine fetal
      deaths (IUFD) cases) contributed to 26 cases (10.7%). Viable pregnancies were
      nine; incomplete abortions, nine; DUB, seven; Non-viable pregnancies, six;
      Threatened abortions, four; PID, four; complete abortions, two; Query-infected or
      degenerating fibroids, two; and others two. Threatened abortion ranked the
      highest among the definite clinical diagnoses. CONCLUSIONS: Bleeding per vaginam
      ranked the highest among GEPC/LACS in this environment, while there was poor
      correlation between clinical impressions and USS findings.

PMID- 21860145
TI  - Hepatitis C virus infection in patients with oral lichen planus.
AB  - BACKGROUND: Lichen planus (LP) is a chronic mucocutaneous disease of uncertain
      etiology. Recent reports suggest that LP is an extrahepatic manifestation of
      Hepatitis C infection. OBJECTIVE: To determine the association of Hepatitis C
      virus (HCV) infection with oral LP and to study the tests of liver function in
      patients with oral LP. STUDY DESIGN: A cross-sectional case-control study was
      carried out on 25 patients with oral LP and an equal number of controls. The
      study was conducted in the outpatient department of a dental college for a period
      of six months between January and June 2008. The sera of the patients and
      controls were tested for HCV ribonucleic acid (RNA) using reverse transcription
      primed-polymerase chain reaction and liver function tests (bilirubin,
      transaminases, and alkaline phosphatase). RESULTS: Of the 25 patients with LP,
      three (12%) had HCV infection. None of the controls had HCV RNA positivity ( P =
      0.2347). Oral LP patients had higher serum bilirubin and transaminases when
      compared with controls ( P < 0.05). However, there was no significant difference
      in alkaline phosphatase. HCV-positive and -negative patients did not differ
      significantly in liver function tests. CONCLUSIONS: An increased prevalence of
      HCV infection was seen in oral LP patients. Our findings support a possible
      etiological association between these two diseases.

PMID- 21860146
TI  - Neck masses in children: etiopathology in a tertiary center.
AB  - BACKGROUND: Neck masses are common in children; they could present diagnostic
      challenges, and some may be malignant. This study determines the etiology,
      histopathology, and outcome of treatment in a Nigerian tertiary center. MATERIALS
      AND METHODS: This is a three-year retrospective study of children managed with
      neck masses at the University of Benin Teaching Hospital between January 2007 and
      December 2009. The biodata, side distribution of the masses, clinical conditions
      of the children at presentation, methods of biopsy, histopathology results,
      definitive treatment options, follow-up, and outcome were analyzed. RESULTS: A
      total of 35 children who were aged between one month and 16 years (mean, 8.1 +/-
      2.6 years) with a male : female ratio of 1.9 : 1 (23 males to 12 females) were
      managed with 26 (74.3%) acquired and nine (25.7%) congenital neck masses. The
      masses were located in the anterior triangle in 14 (40%) cases, right side of the
      neck in 12 (34.3%), and left side of the neck in seven (20%), with two (5.7%)
      bilateral/confluent. Twelve (34.3%) cases were enlarged lymph nodes; five (41.7%)
      of them due to malignant lesions. Except for the neck mass, 16 (45.7%) of the
      children enjoyed clinically stable health on presentation. Twenty (57.1%)
      acquired tumors were malignant compared with 15 (42.9%) mainly congenital tumors
      which were benign. Four malignant tumors (11.4%) were rare in anterior triangle.
      Hodgkin's lymphoma, 9 (25.7%), and thyroglossal duct cyst, 5 (14.3%), were most
      common malignant and nonmalignant masses, respectively. Surgical excision was
      curative in 12 (34.3%) cases, but others required additional chemo and/or
      radiotherapy, with two (5.7%) mortality recorded due to late referral of children
      with Hodgkin's lymphoma. CONCLUSIONS: Many neck masses in otherwise healthy
      children in our setting were malignant. We advocate early surgical consultation
      and thorough histopathologic analysis of neck masses in children in our
      subregion.

PMID- 21860147
TI  - Home management of childhood diarrhoea: need to intensify campaign.
AB  - A review of home management of childhood diarrhea in under-five children among
      203 Nigerian mothers was carried out over a period of 3 months in order to
      ascertain how effectively they manage their children with diarrhea outside a
      hospital setup (infrastructural health facility). Mothers whose children had
      diarrhea, with or without other symptoms, and presented at the Children's Out
      Patient unit (CHOP), of the UNTH over the study period were consecutively
      interviewed through a questionnaire designed for the study. The questionnaires
      were designed and administered by the authors. There were 30 mothers in social
      class 1; 59 in social class 2; 52 in social class 3; 13 in social class 4, and 7
      mothers in social class 5. Information was obtained on the method of detection,
      causes of diarrhea, and treatment including their knowledge and use of oral
      rehydration salts with or without anti diarrheal and antibacterial agents. Out of
      the 203 mothers interviewed, 140 (71%) correctly defined diarrhea. 112 (55.2%)
      could identify correct causes of childhood diarrhea. Only 80 (39.4%) could
      correctly manage diarrhea at home. About 76% (154 mothers) knew that they should
      use an oral rehydration salt; of this number, 56 (27.6%) could correctly prepare
      SSS, while 29 (14.3%) could do the same for the UNICEF ORS. In addition, anti
      bacterial, anti-diarrheal, and/or herbal preparations were used by 38 (18.7%) of
      the mothers. The level of knowledge of oral rehydration therapy has dropped in
      our locality since its inception in the early 1990s. There is need to intensify
      maternal education in this area since we now have a new generation of mothers who
      were not there during the inception of the program.

PMID- 21860148
TI  - Osteolipoma of the palate: report of a case and review of the literature.
AB  - Oral lipomas, though rare, predominantly affect the buccal mucosa, tongue, and
      lips. The occurrence of lipomas in the palate is extremely rare. Osteolipoma is a
      very rare histological variant of lipoma accounting for less than 1% of all
      cases. Although a few cases involving the soft palate have been reported, there
      is only one reported case of osteolipoma of the hard palate in the English
      language literature and it was a congenital osteolipoma associated with a cleft
      palate in a 6-year-old male child. This paper aims to describe an additional case
      uniquely located in the hard palate of an adult female.

PMID- 21860149
TI  - Congenital gangrene of the extremities in a newborn.
AB  - Gangrene of the extremities in the newborn is extremely rare at birth. Less than
      100 cases have been reported worldwide. Its etiology is obscure in many cases;
      however, some factors have been associated with it in the newborn, which include
      vascular injury and embolism. We report a case of a baby with congenital
      bilateral lower limb gangrene caused by thromboembolic phenomenon from
      retroplacental hematoma following abruptio placentae and highlight the challenges
      of managing such condition in resource-poor setting.

PMID- 21860150
TI  - Congenital aganglionic megacolon in Nigerian adults: two case reports and review
      of the literature.
AB  - Congenital aganglionic mega colon (Hirschsprung's disease) is a motor disorder in
      the gut, due to a defect in the craniocaudal migration of the neuroblast
      originating from the neural crest that occurs during the first twelve weeks of
      gestation, causing a functional intestinal obstruction, with its attendant
      complications, in infants. Despite modern pediatric practice, with emphasis on
      early diagnosis, Hirschsprung's disease is seen in adults in regions where
      perinatal care is limited. We report two cases of Nigerian adults with
      longstanding, recurrent constipation, getting relieved by laxatives and herbal
      enemata, and then presented to our Emergency Department with a history of
      progressive abdominal distention, colicky pain, occasional vomiting, and weight
      loss. Per rectal examination revealed a gripping sensation in the rectum, 10 cm
      from the anal verge, with rectal fecal load. Barium enema showed a grossly
      distended proximal large colon, with high fecal retention, with the transition
      zone at the middle one-third of the rectum. Due to difficulty in bowel
      preparation of these patients, emergency laparotomy was done. The first case had
      a diverting sigmoid colostomy and later had a low anterior resection. The second
      case had a one-stage procedure. Histology of both the cases showed aganglionosis
      of the stenotic segment and a normal distal rectum. Both patients had complete
      resolution of the symptoms, without complications, in a three-year follow-up. The
      related literatures were reviewed. Hirschsprung's disease should be considered in
      adults patient presenting with chronic constipation. Low anterior resection of
      the rectum would be a surgical option for the treatment of short and zonal
      segment of adult Hirschsprung's disease.

PMID- 21860151
TI  - Monitoring methotrexate hepatotoxicity in psoriasis.

PMID- 21860152
TI  - Is leprosy 'elimination' a conceptual illusion?

PMID- 21860153
TI  - Facial melanoses: Indian perspective.
AB  - Facial melanoses (FM) are a common presentation in Indian patients, causing
      cosmetic disfigurement with considerable psychological impact. Some of the well
      defined causes of FM include melasma, Riehl's melanosis, Lichen planus
      pigmentosus, erythema dyschromicum perstans (EDP), erythrosis, and poikiloderma
      of Civatte. But there is considerable overlap in features amongst the clinical
      entities. Etiology in most of the causes is unknown, but some factors such as UV
      radiation in melasma, exposure to chemicals in EDP, exposure to allergens in
      Riehl's melanosis are implicated. Diagnosis is generally based on clinical
      features. The treatment of FM includes removal of aggravating factors, vigorous
      photoprotection, and some form of active pigment reduction either with topical
      agents or physical modes of treatment. Topical agents include hydroquinone (HQ),
      which is the most commonly used agent, often in combination with retinoic acid,
      corticosteroids, azelaic acid, kojic acid, and glycolic acid. Chemical peels are
      important modalities of physical therapy, other forms include lasers and
      dermabrasion.

PMID- 21860155
TI  - Late onset vitiligo and audiological abnormalities: is there any association?
AB  - BACKGROUND: There is scarce published data on late onset vitiligo. All the
      studies showing association of audiological abnormalities have been done on
      younger age group of patients. AIM: To study the clinical characteristics of the
      patients with late onset vitiligo. Also, to investigate the audiological
      abnormalities seen in these patients and compare them with age and sex matched
      healthy volunteers. METHODS: One hundred and ninety-seven consecutive patients
      developing vitiligo after the age of 40 were studied. These patients were
      examined for the audiological abnormalities, and compared with those seen in age
      and sex matched healthy volunteers. RESULTS: Vitiligo started between 40 and 50
      years of age in 68.02% of our patients. Vitiligo vulgaris was the commonest
      clinical pattern, and most patients reported onset of their vitiligo on the upper
      extremities. Fifty four had diabetes mellitus, 19 patients had autoimmune thyroid
      diseases, and 32 showed hypoacusis on audiometric examination. Eighteen controls
      (age and sex matched healthy volunteers) also showed hypoacusis. The difference
      in frequency was not significant (22.37% vs 18%, chi2-test, P>0.05). The
      sensorineural type of audiologic impairment was more commonly seen both in
      patients as well as in controls. CONCLUSION: Late onset vitiligo was not found to
      have statistically significant association with audiological abnormalities in
      this study.

PMID- 21860154
TI  - 1064 nm Q switched Nd: YAG laser treatment of nevus of Ota: an Indian open label
      prospective study of 50 patients.
AB  - BACKGROUND: Nevus of Ota is very common in Asians. Estimated male to female ratio
      is 1:4.8. Patients seek treatment early in life due to psychological trauma and
      cosmetic disfigurement. The creation of high power, short pulse Q switched lasers
      has recently provided tools for considerable therapeutic advances in the
      treatment of dermal pigmented lesions. AIMS: To determine the efficacy and side
      effect profile of Q switched Nd:YAG Laser (QSNYL) in fifty Indian patients.
      METHODS: Fifty patients of nevus of Ota underwent multiple treatments (average 5
      sessions) at monthly intervals carried out over a period of 2 years with QSNYL
      (Med-lite C6). Of the 50 patients, 2 were males; and the rest were females. Skin
      types treated included phototype IV and V. The response after subsequent
      treatments was documented through serial photographs that were taken before and
      after every treatment session. Response to the treatment was graded based on
      quartile grading scale. RESULTS: Near total improvement was seen in 8%, marked
      improvement in 22%, moderate improvement in 38% and 32% patients reported less
      than 25% clearing of the lesion. All patients reported some improvement.
      Transient postinflammatory hyperpigmentation was observed in 4 (8%) patients,
      which cleared with use of sunscreens and bleaching agents within 2 months. No
      textural change or scarring was observed in any patient. CONCLUSIONS: QSNYL is an
      easy-to-perform and effective treatment in cases of nevus of Ota in Indian
      patients with few side effects.

PMID- 21860156
TI  - Skin tags, leptin, metabolic syndrome and change of the life style.
AB  - BACKGROUND: Skin tags (STs), are papillomas commonly found in the neck and in the
      axillae of middle-aged and elderly people. Metabolic syndrome (MS) is a complex
      of interrelated risk factors for cardiovascular disease and diabetes.
      Epidemiologic studies of different ethnic populations have indicated that
      hyperleptinaemia and leptin resistance are strongly associated with MS. AIM: To
      study the possible relation of skin tags and leptin levels to MS guided by the
      International Diabetes Federation (IDF) diagnostic criteria. METHODS: This study
      included 80 participants, 40 ST patients and 40 apparently healthy controls. Age,
      sex, waist circumference (WC), body mass index (BMI), smoking status, fasting
      glucose level, insulin level and insulin resistance were estimated as well as
      cholesterol, triglycerides, HDL, criteria of MS, and leptin levels. RESULTS: The
      univariate analysis showed that WC, BMI, fasting glucose, insulin levels, insulin
      resistance, cholesterol, triglycerides, HDL, and leptin levels were significantly
      higher in ST patients compared to controls (P<0.001). The multivariate analysis
      between MS components and ST showed that only high triglyceride levels (OR
      1.205/95% CI 1.044-1.391/P=0.011) and low HDL levels (OR 0.554/95% CI 0.384
      0.800/P=0.002) were significantly associated with ST. Multivariate linear
      regression analysis of the predictors of high plasma leptin levels, showed that
      high triglyceride levels (OR 0.287/95% CI 0.410-3.56/P=0.014), and low HDL levels
      (OR -0.404/95% CI -8.7 to -2.08/P=0.002) were significant predictors. CONCLUSION:
      The results of this study suggested that the presence of both ST and
      hyperleptinaemia in patients with STs may be associated with high levels of
      triglycerides and low levels of HDL and this could suggest that changing the life
      style of patients with ST may have a beneficial role.

PMID- 21860157
TI  - Topical permethrin and oral ivermectin in the management of scabies: a
      prospective, randomized, double blind, controlled study.
AB  - BACKGROUND: Scabies is a highly contagious and intensely pruritic parasitic
      infestation. It is a re-emerging infection in the new millennium especially with
      HIV pandemic and a significant health problem in developing countries. Various
      treatment modalities have been used since time immemorial but the search for an
      ideal scabicide is ongoing. AIMS: In this study, we compared the therapeutic
      efficacy of single application of topical 5% permethrin with oral ivermectin (200
      MUg/kg/dose) in a single-dose and a two-dose regimen in patients with scabies.
      METHODS: 120 clinically diagnosed cases of scabies (>5 years of age and/or >15
      kg) were randomized into three treatment groups A, B, C of 40 patients each;
      receiving either topical 5% permethrin (group A) or oral ivermectin (200
      MUg/kg/dose) in a single dose (group B) or double dose regimen (group C) repeated
      at 2 weeks interval. Patients were followed up at 1, 2, and 4 weeks interval. At
      each visit, cure rate (>50% improvement in lesion count and pruritus and negative
      microscopy) was assessed and compared. RESULTS: Cure rate in three treatment
      groups at the end of 4 weeks was 94.7% (A), 90% (B), 89.7% (C), and thus all
      three treatment modalities were equally efficacious. However, at 1 week follow
      up, group A patients reported better improvement in both lesion count and
      pruritus. CONCLUSIONS: Both permethrin and ivermectin in both single and two dose
      regimen are equally efficacious and well tolerated in scabies. However,
      permethrin has a rapid onset of action.

PMID- 21860158
TI  - Langerhans cell histiocytosis: an uncommon presentation, successfully treated by
      thalidomide.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease and generally affects
      children under 15 years of age. Adult onset form and cutaneous features at
      presentation are uncommon. There are some options for treatment of the skin
      lesions of LCH such as topical and intralesional corticosteroid, nitrogen
      mustard, etc., which are not completely curative. Herein, we report a case of
      perianal LCH in a 20-year-old man with one-year history of recalcitrant well
      demarcated, erythematous, and ulcerated plaque surrounding the anal orifice, with
      pain and difficulty in defecation that was successfully treated with thalidomide.

PMID- 21860159
TI  - White piedra of scalp hair by Trichosporon inkin.
AB  - White piedra is a rare fungal infection of hair and is reported to be all the
      more rare on scalp. Trichosporon inkin is usually associated with white piedra of
      pubic hair. We report a case of white piedra of scalp hair caused by T. inkin.
      This is the first case reported from India and the fifth case reported worldwide.
      A 50-year-old Muslim female presented with white knots over scalp hair. Diagnosis
      of Trichosporon was made by examining KOH mounts of epilated hair and Lactophenol
      Cotton Blue preparations of the growth in culture. Automated mini-API test (for
      biochemical profiles) and Electronmicroscopy studies (for cell wall structures)
      helped in identification of the species. Mini-API test was also positive for
      Cryptococcus curvatus which could be due to similarity in biochemical and
      physiological properties of the two species. Absence of C. curvatus on culture
      further supports this view. Topical antifungal therapy resulted in clinical
      clearance within 2 months. Higher incidence of scalp white piedra is observed in
      Muslim females; contributing factor being the custom of using a veil, leading to
      higher humidity and limited sunlight exposure.

PMID- 21860160
TI  - Multiple isolated cutaneous plexiform schwannomas.
AB  - Plexiform schwannoma is a rare neurogenic tumor, arising from skin and
      subcutaneous tissue. The presence of multiple schwannomas suggests a possible
      association with neurofibromatosis type 2 (NF2). A 50-year old male patient
      presented with multiple papulo-nodular cutaneous lesions on both arms and
      forearms. Histopathological examination revealed a dermal multinodular pattern of
      well-circumscribed masses of closely packed cells, with peripheral myxoid tissue,
      well-encapsulated in a thin collagenous capsule. S-100 immunohistochemical
      staining was diffusely and strongly positive. Neuron-specific enolase was
      positive, confirming a neural tissue tumor. An audiogram and Magnetic Resonance
      Imaging (MRI) of cerebro-pontine angle showed no detected abnormality, excluding
      acoustic neuroma. Thus, we present a case of multiple bilateral isolated
      cutaneous plexiform schwannomas, not associated with NF2. Multiple plexiform
      schwannomas is a very rare entity, distinct from neurofibromatosis (NF), and
      being confined to the dermis is even more rarely reported.

PMID- 21860161
TI  - Progressive symmetric erythrokeratoderma: report of a Chinese family.
AB  - A large pedigree of progressive symmetric erythrokeratoderma is reported. The
      proband was a 22-year-old male with generalized asymptomatic lesions
      characterized by symmetrical well-demarcated erythematous hyperkeratotic plaques
      mainly distributed on the extremities. The proband's parents were also affected,
      and they were first cousins. Thus, a case of familial progressive symmetric
      erythrokeratoderma is described.

PMID- 21860162
TI  - Giant porokeratosis.

PMID- 21860163
TI  - Pattern of skin diseases in Kumaun region of Uttarakhand.

PMID- 21860164
TI  - Study of the density and distribution of Mycobacterium leprae in the epidermis
      and skin appendages in lepromatous patients.

PMID- 21860165
TI  - Extensive, adulthood inflammatory linear verrucous epidermal nevus associated
      with mucinous nevus.

PMID- 21860166
TI  - Sister Mary Joseph's nodule derived from lung cancer.

PMID- 21860167
TI  - Sudden irreversible worsening of myopia with isotretinoin treatment.

PMID- 21860168
TI  - Contact depigmentation following irritant contact dermatitis to chloroxylenol
      (Dettol).

PMID- 21860170
TI  - Isolated unilateral palisaded neutrophilic and granulomatous dermatitis.

PMID- 21860169
TI  - Psoriasiform skin eruption associated with sorafenib therapy.

PMID- 21860171
TI  - Using a simple jeweler's loupe as a dermoscopic instrument.

PMID- 21860172
TI  - Hereditary angioedema: an update.

PMID- 21860173
TI  - Psychiatric morbidity in psoriasis patients: a pilot study.

PMID- 21860174
TI  - Palmoplantar involvement in psoriasis: a clinical study.

PMID- 21860175
TI  - Trichophyton rubrum onychomycosis in an 8-week-old infant.
AB  - An 8-week-old infant presented with 7 weeks history of nail involvement and
      discoloration. Lesions started over the middle fingernail of right hand at 1 week
      of age, spreading over to other nails within 2 weeks. Only two nails of the feet
      were spared. On KOH examination, fungal hyphae were seen and culture showed
      growth of Trichophyton rubrum. The purpose is to report the earliest case of
      onychomycosis having multiple nail involvement of fingers and toes (18 nails).

PMID- 21860176
TI  - Localized bullous pemphigoid at urostomy site.
AB  - Localized bullous pemphigoid occurs in less than one-third of the cases of
      bullous pemphigoid and it usually appears on the shins. Localized bullous
      pemphigoid around a stoma site is very uncommon, with few reports in the
      literature. We report a case of localized bullous pemphigoid at urostomy site and
      we review its main characteristics. We highlight the importance of considering
      bullous pemphigoid in chronic bullous lesions on peristomal skin.

PMID- 21860177
TI  - A myriad of paraneoplastic dermatoses.

PMID- 21860178
TI  - Cutaneous aspergilloma in an immunocompetent patient treated with itraconazole.

PMID- 21860179
TI  - Metastasizing squamous cell carcinoma arising from chronic discoid lupus
      erythematosus plaque of recent onset.

PMID- 21860180
TI  - Microsporum canis tinea capitis in a centenarian patient.

PMID- 21860181
TI  - Cutaneous changes associated with prolonged plaster of Paris immobilization.

PMID- 21860182
TI  - Papulovesicular eruption located on the face and extremities in a child.
      Diagnosis: hydroa vacciniforme.

PMID- 21860183
TI  - Dermatosis neglecta unmasking recurrence of carcinoma nasopharynx.

PMID- 21860184
TI  - Epidermoid cyst of penis.

PMID- 21860185
TI  - Multiple congenital vascular lesions in a child.

PMID- 21860186
TI  - Transesophageal echocardiography: rapid expansion in perioperative medicine in
      emerging economies--are we ready for a safe and effective practice?

PMID- 21860187
TI  - Heart transplantation in the era of continuous flow ventricular assist devices
      and the total artificial heart: will new technologies surpass the gold standard?

PMID- 21860188
TI  - Effect of prophylactic amiodarone in patients with rheumatic valve disease
      undergoing valve replacement surgery.
AB  - The study was carried out to evaluate the effect of prophylactic single-dose
      intravenous amiodarone in patients undergoing valve replacement surgery.
      Maintenance of sinus rhythm is better than maintenance of fixed ventricular rate
      in atrial fibrillation (AF) especially in the presence of irritable left or right
      atrium because of enlargement. Fifty-six patients with valvular heart disease
      with or without AF were randomly divided into two groups. Group I or the
      amiodarone group (n=28) received amiodarone (3 mg/kg in 100 ml normal saline) and
      group II or the control group received same volume of normal saline. The
      standardized protocol for cardiopulmonary bypass was maintained for all the
      patients. AF occurred in 7.14% patients in group I, and in group II, 28.57%
      (P=0.035); ventricular tachycardia/fibrillation was observed in 21.43% patients
      in group I and 46.43% patients in group II (P=0.089) after release of aortic
      clamp. Most of the patients in group I (92.86%) maintained sinus rhythm without
      cardioversion or defibrillation after release of aortic cross clamp (P=0.002).
      Defibrillation or cardio version was needed in 7.14% patients in group I and
      28.57% patients in group II (P=0.078). A single prophylactic intraoperative dose
      of intravenous amiodarone decreased post bypass arrhythmia in this study in
      comparison to the control group. Single dose of intraoperative amiodarone may be
      used to decrease postoperative arrhythmia in open heart surgery.

PMID- 21860190
TI  - Intra-aortic balloon pump use does not affect the renal function in patients
      undergoing off pump coronary artery bypass surgery.
AB  - Renal dysfunction is known to occur during cardiac surgery. A few factors such as
      perioperative hypotension, use of potential nephrotoxic therapeutic agents, radio
      opaque contrast media in the recent past, intra-aortic balloon pump (IABP) and
      cardiopulmonary bypass have been blamed as the contributing factors to the
      causation of postoperative renal dysfunction in cardiac surgical patients. At
      times, in patients with renal failure and low cardiac output status, one may face
      the dilemma if the use of IABP is safe. We undertook this prospective
      observational study to determine the degree of possible renal injury when IABP is
      used by measuring serial values of serum creatinine and Cystatin C. Elective
      patients scheduled for off-pump coronary artery bypass surgery requiring
      preoperative use of IABP were included in this study. Cystatin C and serum
      creatinine levels were checked at fixed intervals after institution of IABP.
      Twenty-two patients were eligible for enrolment to the study. There was no
      significant change in the values of serum creatinine; from the basal value of
      1.10 +/- 0.233 to 0.98 +/- 0.363 mg /dL (P value >0.05). Cystatin C levels
      significantly decreased from the basal level of 0.98 +/- 0.29 to 0.89 +/- 0.23 (P
      value <0.05). Contrary to the belief, Cystatin C, the early indicator of renal
      dysfunction decreases suggesting absence of renal injury after the use of IABP.
      Absence of elevation of cystatin C levels in our study suggests the lack of
      potential of the IABP to cause renal dysfunction in patients who received
      elective IABP therapy preoperatively.

PMID- 21860189
TI  - Positive end expiratory pressure during one-lung ventilation: selecting ideal
      patients and ventilator settings with the aim of improving arterial oxygenation.
AB  - The efficacy of positive end-expiratory pressure (PEEP) in treating
      intraoperative hypoxemia during one-lung ventilation (OLV) remains in question
      given conflicting results of prior studies. This study aims to (1) evaluate the
      efficacy of PEEP during OLV, (2) assess the utility of preoperative predictors of
      response to PEEP, and (3) explore optimal intraoperative settings that would
      maximize the effects of PEEP on oxygenation. Forty-one thoracic surgery patients
      from a single tertiary care university center were prospectively enrolled in this
      observational study. After induction of general anesthesia, a double-lumen
      endotracheal tube was fiberoptically positioned and OLV initiated.
      Intraoperatively, PEEP = 5 and 10 cm H(2)O were sequentially applied to the
      ventilated lung during OLV. Arterial oxygenation, cardiovascular performance
      parameters, and proposed perioperative variables that could predict or enhance
      response to PEEP were analysed. T-test and chi(2) tests were utilized for
      continuous and categorical variables, respectively. Multivariate analyses were
      carried out using a classification tree model of binary recursive partitioning.
      PEEP improved arterial oxygenation by >=20% in 29% of patients (n = 12) and
      failed to do so in 71% (n = 29); however, no cardiovascular impact was noted.
      Among the proposed clinical predictors, only intraoperative tidal volume per
      kilogram differed significantly between responders to PEEP and non-responders
      (mean 6.6 vs. 5.7 ml/kg, P = 0.013); no preoperative variable predicted response
      to PEEP. A multivariate analysis did not yield a clinically significant model for
      predicting PEEP responsiveness. PEEP improved oxygenation in a subset of
      patients; larger, although still protective tidal volumes favored a positive
      response to PEEP. No preoperative variables, however, could be identified as
      reliable predictors for PEEP responders.

PMID- 21860191
TI  - Effect of thoracic epidural anesthesia on oxygen delivery and utilization in
      cardiac surgical patients scheduled to undergo off-pump coronary artery bypass
      surgery: a prospective study.
AB  - To evaluate the effect of thoracic epidural anesthesia (TEA) on tissue oxygen
      delivery and utilization in patients undergoing cardiac surgery. This prospective
      observational study was conducted in a tertiary referral heart hospital. A total
      of 25 patients undergoing elective off-pump coronary artery bypass surgery were
      enrolled in this study. All patients received thoracic epidural catheter in the
      most prominent inter-vertebral space between C7 and T3 on the day before
      operation. On the day of surgery, an arterial catheter and Swan Ganz catheter
      (capable of measuring cardiac index) was inserted. After administering full dose
      of local anesthetic in the epidural space, serial hemodynamic and oxygen
      transport parameters were measured for 30 minute prior to administration of
      general anesthesia, with which the study was culminated. A significant decrease
      in oxygen delivery index with insignificant changes in oxygen extraction and
      consumption indices was observed. We conclude that TEA does not affect tissue
      oxygenation despite a decrease in arterial pressures and cardiac output.

PMID- 21860193
TI  - Entropy score, patent ductus arteriosus (PDA), and cardiopulmonary bypass (CPB):
      ligation of PDA on CPB can compromise cerebral blood flow.
AB  - A patent ductus arteriosus (PDA) is often present in patients undergoing
      correction of congenital heart disease. It is well appreciated that during
      cardiopulmonary bypass (CPB), a PDA steals arterial inflow into pulmonary
      circulation, and may lead to systemic hypoperfusion, excessive pulmonary blood
      flow (PBF) and distention of the left heart. Therefore, PDA is preferably ligated
      before initiation of CPB. We describe acute decreases of arterial blood pressure
      and entropy score with the initiation of CPB and immediate increase in entropy
      score following the PDA ligation in a child undergoing intracardiac repair of
      ventricular septal defect and right ventricular infundibular stenosis. The
      observation strongly indicates that a PDA steals arterial inflow into pulmonary
      circulation and if the PDA is dissected and ligated on CPB or its ligation on CPB
      is delayed the cerebral perfusion is potentially compromised.

PMID- 21860192
TI  - Comparison of S100beta levels, and their correlation with hemodynamic indices in
      patients undergoing coronary artery bypass grafting with three different
      anesthetic techniques.
AB  - Cardiac surgery with aid of cardiopulmonary bypass (CPB) is associated with
      neurological dysfunction. The presence of cerebrospecific protein S100beta in
      serum is an indicator of cerebral damage. This study was designed to evaluate the
      influence of three different anesthesia techniques, on S100beta levels, in
      patients undergoing coronary artery bypass grafting on CPB. A total of 180
      patients were divided into three groups - each of who received sevoflurane,
      isoflurane and total intravenous anesthesia as part of the anesthetic technique,
      respectively. S100 were evaluated from venous sample at following time intervals 
      prior to induction of anesthesia (T1), after coming off CPB (T2); 12 h after
      aortic cross clamping (T3) and 24 h after aortic cross clamping (T4). In all
      three groups, maximal rise in S100beta levels occurred after CPB which gradually
      declined over next 24 h, the levels at 24 h post-AOXC being significantly higher
      than baseline levels. Significantly low levels of S100beta were noted at all
      postdose hours in the sevoflurane group, as compared to the total intravenous
      anesthesia (TIVA) group, and at 12 and 24 h postaortic cross clamp, in comparison
      to the isoflurane group. Comparing the isoflurane group with the TIVA group, the
      S100 levels were lower in the isoflurane group only at 24 h postaortic cross
      clamp. It was concluded that maximum rise in S100beta levels occurs immediately
      after CPB with a gradual decline in next 24 h. The rise in S100beta levels is
      significantly less in patients administered sevoflurane in comparison to
      isoflurane or TIVA. Hemodynamic parameters had no influence on the S100beta
      levels during the first 24 h after surgery.

PMID- 21860194
TI  - Sudden decrease in end-tidal carbon-dioxide in a neonate undergoing surgery for
      type B interrupted aortic arch.
AB  - Interruption of the aortic arch is a rare anomaly affecting 1% of children with
      congenital heart disease. The systemic circulation is ductal dependent and is
      determined principally by the ratio of the resistances in the systemic and the
      pulmonary vascular bed. Any increase in the pulmonary vascular resistance may
      increase the dead space ventilation due to acute pulmonary hypoperfusion. We
      report a case where sudden decreases in the end-tidal carbon-dioxide due to
      pulmonary hypoperfusion mimicked accidental endotracheal tube extubation in an
      infant undergoing repair of interrupted aortic arch.

PMID- 21860195
TI  - Successful double lumen tube insertion in a patient with unanticipated laryngeal
      and tracheal web.
AB  - A 45-year-old female patient admitted for surgical management of carcinoma
      esophagus, presented with difficulty in insertion of left-sided 37 F and 35 F
      double lumen tube (Mallinckrodt(r) Broncho-Cath). Fiberoptic bronchoscopy
      revealed a subglottic web in the larynx just below the vocal cords and a tracheal
      web just above the carina. Differential lung ventilation could be achieved with a
      35 F internal diameter double lumen tube (Portex(r) Blueline(r) Endobronchial
      tube).

PMID- 21860196
TI  - Noonan syndrome: an anesthesiologist's perspective.
AB  - Noonan syndrome (NS) is one of the most common non chromosomal syndrome
      presenting to the cardiac anesthesiologist for the management of various cardiac
      lesions, predominantly pulmonary stenosis (PS) (80%) and hypertrophic obstructive
      cardiomyopathy (HOCM) (30%). The presence of HOCM in NS makes these children
      susceptible to acute congestive heart failure due to hemodynamic fluctuations,
      thus necessitating optimization of drug and fluid therapy, careful conduct of
      anesthesia and providing adequate analgesia in the perioperative period. We
      describe a case of four year old boy with NS who presented to us for the
      management of PS and HOCM. In our case, transesophageal echocardiography (TEE)
      played a major role in confirmation of the preoperative findings, detection of
      any new anomalies missed during the preoperative evaluation, intraoperative
      monitoring and assessment of the adequacy of repair in the immediate
      postoperative period. TEE provided invaluable help in taking critical surgical
      decisions, resulting in a favorable outcome.

PMID- 21860197
TI  - Extracorporeal membrane oxygenation, an anesthesiologist's perspective:
      physiology and principles. Part 1.
AB  - Extracorporeal membrane oxygenation (ECMO) is an adaptation of conventional
      cardiopulmonary bypass techniques to provide cardiopulmonary support. ECMO
      provides physiologic cardiopulmonary support to aid reversible aspects of the
      disease process and to allow recovery. ECMO does not provide treatment of the
      underlying disease. The indications for ECMO support have expanded from acute
      respiratory failure to acute cardiac failure refractory to conventional
      treatments from wide patient subsets involving neonates to adults. Vascular
      access for ECMO support is either percutaneous through a single-site, dual-lumen
      bicaval cannula or transthoracic via separate cannulas. The modes of support are
      either veno-venous or veno-arterial ECMO. In this article, the physiologic
      aspects of ECMO support are outlined.

PMID- 21860198
TI  - TEE images of aorto-pulmonary (central) shunt.

PMID- 21860199
TI  - Anesthetic management for successful removal of intratracheal tumor.

PMID- 21860200
TI  - Double valve replacement in a patient with antiphospholipid antibody syndrome.

PMID- 21860201
TI  - Complete recovery from paraplegia following apparently failed cerebrospinal fluid
      drainage in a case of thoracoabdominal aortic aneurysm repair.

PMID- 21860202
TI  - Anesthesia for simultaneous bilateral aorto-axillary and coronary artery bypass
      grafting in Takayasu's arteritis.

PMID- 21860203
TI  - Use of integrated extracorporeal membrane oxygenator in anomalous left coronary
      artery to pulmonary artery: better survival benefit.

PMID- 21860204
TI  - Remifentanil: much ado about something.

PMID- 21860205
TI  - Perioperative blood pressure management: walking a tightrope.

PMID- 21860206
TI  - Dengue fever in a patient recovering from coronary artery bypass grafting.

PMID- 21860207
TI  - Have we something to replace evidence based medicine?

PMID- 21860208
TI  - CHD5 Downregulation Associated with Poor Prognosis in Epithelial Ovarian Cancer.
AB  - BACKGROUND: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase
      DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene
      candidate. This study investigated the involvement of CHD5 in ovarian cancer and
      its clinicopathological significance. METHODS: CHD5 expression in ovarian cancer
      and its counterpart were determined by quantitative RT-PCR. The correlation of
      CHD5 expression to clinicopathological features of the tumor was analyzed.
      RESULTS: CHD5 expression was downregulated by at least twofold in 32 of 72 (41%)
      invasive epithelial ovarian carcinomas when compared to 12 controls in Hong Kong
      Chinese women. CHD5 downregulation was correlated to clinical status (p < 0.05),
      but not to patient age, tumor type and grade, recurrence and clinical stage (p >
      0.05). Survival analysis showed that patients with CHD5 downregulation in their
      tumors were associated with shorter disease-free and total survival times
      compared to those without CHD5 downregulation (p < 0.05). Cox proportional
      hazards regression analysis indicated that downregulation of CHD5 is an
      independent adverse prognostic factor in ovarian cancer. CONCLUSION: This study
      shows that CHD5 is downregulated in a certain number of ovarian cancers and
      appears to be an adverse predictor candidate of ovarian cancer disease-free and
      total survival.

PMID- 21860209
TI  - Robotic radical parametrectomy in cervical cancer.
AB  - Radical parametrectomy is indicated in cases of undiagnosed early-stage invasive
      cervical carcinoma discovered after simple hysterectomy performed for a presumed
      benign disease process. This radical surgical procedure is rarely performed for
      benign disease; however, there are some benign conditions such as endometriosis
      or ovarian remnant syndrome which may require wide excision, including
      parametria. Traditionally, radical parametrectomy has been performed via
      laparotomy; however, a minimally invasive approach via laparoscopy has been
      reported to be feasible and safe. Here we describe the robotic surgical approach
      to radical parametrectomy.

PMID- 21860210
TI  - Virtual bladder tumor transurethral resection: an objective evaluation tool to
      overcome learning curves with and without photodynamic diagnostics.
AB  - INTRODUCTION: Virtual reality (VR) simulation has been known to shorten learning
      curves. The aim of this research was to determine whether VR transurethral
      bladder tumor resection (TURBT) with and without photodynamic diagnostic (PDD)
      can improve endourological skills in novice and trained endoscopists. MATERIALS
      AND METHODS: Residents without experience (n = 15) completed five 5-min white
      light VR-TURBT scenarios. The trained endoscopists (>=25 TURBTs; n = 15)
      performed five 5-min VR resections using white light and PDD cystoscopy. The VR
      TURBT performance with the Uro-Trainer(r) (Karl Storz GmbH, Germany) was compared
      between the first and last 5 cases using computer-generated parameters [inspected
      area (%), resected tumor mass (%) and bleeding (ml)]. The trained endoscopists'
      parameters were compared with white light versus PDD-VR-TURBT. RESULTS: Among
      novices, the inspected area increased from 36.8 (+/-12.9) to 54.3% (+/-7.3), p <
      0.05. Significant improvements were noted for resection rates from 26.5 (+/-9.6)
      to 52.0% (+/-6.0), p < 0.05. Trained urologists showed superior inspection [52.2
      (+/-3.4) vs. 62.7% (+/-4.3), p = 0.003] and resection rates [43.8 (+/-3.3) vs.
      57.1% (+/-5.3), p = 0.002] with PDD. CONCLUSIONS: The opportunity to evaluate
      objective patient-independent measurements establishes the Uro-Trainer as a
      beneficial tool in enhancing TURBT quality. Results demonstrated that novices
      improved their ability to perform complete resection, and the TURBT rates of
      trained urologists were superior in PDD compared with a white light setting.

PMID- 21860211
TI  - Self-organization phenomena in embryonic stem cell-derived embryoid bodies: axis
      formation and breaking of symmetry during cardiomyogenesis.
AB  - Aggregation of embryonic stem cells gives rise to embryoid bodies (EBs) which
      undergo developmental processes reminiscent of early eutherian embryonic
      development. Development of the three germ layers suggests that gastrulation
      takes place. In vivo, gastrulation is a highly ordered process but in EBs only
      few data support the hypothesis that self-organization of differentiating cells
      leads to morphology, reminiscent of the early gastrula. Here we demonstrate that
      a timely implantation-like process is a prerequisite for the breaking of the
      radial symmetry of suspended EBs. Attached to a surface, EBs develop a bilateral
      symmetry and presumptive mesodermal cells emerge between the center of the EBs
      and a horseshoe-shaped ridge of cells. The development of an epithelial sheet of
      cells on one side of the EBs allows us to define an 'anterior' and a 'posterior'
      end of the EBs. In the mesodermal area, first cardiomyocytes (CMCs) develop
      mainly next to this epithelial sheet of cells. Development of twice as many CMCs
      at the 'left' side of the EBs breaks the bilateral symmetry and suggests that
      cardiomyogenesis reflects a local or temporal asymmetry in EBs. The asymmetric
      appearance of CMCs but not the development of mesoderm can be disturbed by
      ectopic expression of the muscle-specific protein Desmin. Later, the bilateral
      morphology becomes blurred by an apparently chaotic differentiation of many cell
      types. The absence of comparable structures in aggregates of cardiovascular
      progenitor cells isolated from the heart demonstrates that the self-organization
      of cells during a gastrulation-like process is a unique feature of embryonic stem
      cells.

PMID- 21860212
TI  - The effect of HMGB1, a damage-associated molecular pattern molecule, on
      polymorphonuclear neutrophil migration depends on its concentration.
AB  - Polymorphonuclear neutrophils (PMN) play a key role in host defenses against
      invading microorganisms but also potentiate inflammatory reactions in case of
      excessive or misdirected responses. Release of the alarmin high-mobility group
      box 1 (HMGB1) by cells that die at an inflammatory site may act as an alert
      signal for the immune system. We studied the effect of HMGB1 on human PMN
      migration, using whole-blood samples to avoid cell activation associated with
      isolation procedures. HMGB1 50-100 ng/ml reduced baseline PMN migration as well
      as formyl-methionyl-leucyl-phenylalanine- and IL-8-induced PMN chemotaxis. This
      inhibitory effect was mediated by the RAGE receptor. In contrast, a higher HMGB1
      concentration (5,000 ng/ml) had a chemoattractant effect on PMN through IL-8
      production. This effect required the engagement of Toll-like receptors 2 and 4 in
      addition to the RAGE receptor. The A box component of HMGB1, which antagonizes
      the endogenous protein, reduced chemotaxis and also strongly inhibited the
      enhancement of PMN migration observed with the highest HMGB1 concentration. In
      contrast, the B box, reported to be the active form of HMGB1, exerted a
      chemoattractant effect. These results strongly point to a key regulatory role of
      HMGB1 in PMN recruitment to inflammatory tissues. The A box component could
      potentially serve to inhibit inappropriate PMN recruitment during chronic
      inflammatory disorders associated with excessive HMGB1 release.

PMID- 21860213
TI  - Immunobiology of intestinal eosinophils - a dogma in the changing?
AB  - Infiltration of eosinophils into the intestinal mucosa is a typical hallmark of
      antiparasite immune responses and inflammatory disorders of the intestinal tract,
      and eosinophils are thought to contribute to these processes by release of their
      cytotoxic granule content. However, utilizing novel tools to study eosinophils,
      it has been recognized that eosinophils are constitutively present in the
      gastrointestinal tract. In addition, as the dogmatic antiparasite function of
      eosinophils has proven difficult to document experimentally, it has become
      increasingly clear that eosinophils are likely to have a more complex role than
      previously appreciated. Thus, the prevailing dogma of eosinophils merely as
      antiparasitic effector cells is changing. Instead, it has been suggested that
      eosinophils can contribute also to several other processes in the intestinal
      mucosa, e.g. local tissue homeostasis and adaptive immune responses. This review
      describes the current knowledge regarding the characteristics and functions of
      intestinal eosinophils, and the regulation of eosinophil trafficking to the
      intestinal mucosa during the steady state and inflammation. Finally, potential
      additional and new roles of intestinal eosinophils in the intestinal mucosal
      immune system are discussed.

PMID- 21860214
TI  - Maximal aerobic power versus performance in two aerobic endurance tests among
      young and old adults.
AB  - BACKGROUND: Aerobic fitness is of great value for reducing risk of mortality and
      cardiovascular diseases. OBJECTIVE: This study evaluated the performance in and
      correlations between a new test (five-minute pyramid test, 5MPT), the six-minute
      walk-test (6MWT) and maximal oxygen uptake (VO2max) among old and young adults.
      METHODS: Forty-four habitually active adults (females and males), 23 old (64-79
      years) and 21 young (20-32 years) participated. In the 5MPT, the participants
      moved back and forth along a short walkway (5.5 m) over boxes (height: 'old
      people' 0.42 m, 'young people' 0.62 m) arranged like an elongated step pyramid
      for 5 min. Power in the pyramid test (5MPT(power)) was calculated as the product
      of numbers of laps, body weight, gravity and highest box level divided by time. A
      6MWT and a maximal cycle ergometer test for direct measurements of VO2max were
      also performed. In all tests heart rate, with on-line electrocardiography, and
      perceived exertion were recorded. RESULTS: There was a strong correlation between
      the 5MPT(power) and VO2max for the entire group studied (r = 0.98), and each of
      the four subgroups old and young females and males separately (r = 0.78-0.98).
      Contrary to several earlier studies, especially involving people with various
      diseases, the present data showed that 6MWT cannot be used to predict VO2max
      among old females and young adults. The correlation with VO2max was weaker for
      the 6MWT than for the 5MPT(power). The relative performance values for the old
      compared to the young (ratio old/young * 100) were considerably lower in
      5MPT(power) and VO2max (47-55%) than in distance and 'work' in the 6MWT (82-86%).
      CONCLUSIONS: The results, with age and gender variations, can be valuable
      information in health-fitness contexts, since measuring physical aerobic capacity
      is very significant in connection with risk evaluations of mortality and various
      diseases. The 5MPT is a rapid, functional, easy and inexpensive tool for
      predicting assessed maximal aerobic power.

PMID- 21860215
TI  - Accumbal 14-3-3zeta protein downregulation is associated with cocaine-conditioned
      memory.
AB  - Cocaine-conditioned memory has been known to cause cocaine craving and relapse,
      while its underlying mechanisms remain unclear. We explored accumbal protein
      candidates responsible for a cocaine-conditioned memory, cocaine-induced
      conditioned place preference (CPP). Two-dimensional gel electrophoresis in
      conjunction with liquid chromatography mass spectrometry analysis was utilized to
      identify accumbal protein candidates involved in the retrieval of cocaine-induced
      CPP. Among the identified candidate proteins, a downregulated 14-3-3zeta protein
      was chosen and confirmed by Western immunoblotting. A polymer-mediated plasmid
      DNA delivery system was then used to overexpress 14-3-3 protein in mouse nucleus
      accumbens before the CPP retrieval tests. Overexpression of accumbal 14-3-3zeta
      protein was found to diminish conditioned cue/context-mediated cocaine-induced
      CPP. In contrast, another isoform of 14-3-3 protein, 14-3-3epsilon protein, did
      not affect conditioned cue/context-mediated cocaine-induced CPP. Overexpression
      of accumbal 14-3-3zeta protein did not produce motor activity-impairing effect or
      alter local dopamine metabolism. Moreover, overexpression of accumbal 14-3-3zeta
      protein did not affect food-induced CPP. These results, taken together, indicated
      that overexpressed accumbal 14-3-3zeta protein specifically decreased conditioned
      cue/context-mediated cocaine memory. Further understanding of the function of
      accumbal 14-3-3zeta protein may shed light on the treatment of cocaine craving
      and relapse.

PMID- 21860216
TI  - Positive experience of a mobile radiography service in nursing homes.
AB  - BACKGROUND: For elderly people living in nursing homes, a transport to hospital
      for a radiological examination can lead to increased anxiety, disorientation and
      other problems related to the new environment. OBJECTIVE: To investigate the
      usefulness of a mobile radiography service for radiological assessment of
      patients in nursing homes from the patient and staff perspectives. METHODS:
      Lightweight equipment with a digital flat-panel detector was used for mobile
      radiography on nursing home patients in their own rooms. Data on patient and
      staff experiences from the service were collected using a questionnaire with
      closed and open-ended questions. Image quality was evaluated by the radiographer
      and a radiologist. RESULTS: The majority of 241 radiography examinations were of
      the musculoskeletal system (94%). Twelve of 123 patients had pathology that
      required hospital treatment, while 22 patients with radiographic pathology could
      be treated locally. The main beneficial factors were security and comfort,
      acceptance from the patients, no need for transportation, no need for staff to be
      absent from the nursing homes. CONCLUSION: Mobile radiography in nursing homes is
      technically feasible, with good image quality. The most beneficial results were
      that patients avoided unnecessary transport back and forth to the hospital, and
      that the majority of patients could be treated locally.

PMID- 21860218
TI  - The protochordate Ciona intestinalis has a protein like full-length vertebrate
      fibrinogen.
AB  - In a recent review, a putative fibrinogen-like protein in the protochordate Ciona
      intestinalis was noted. Unfortunately, computer-directed splicing had omitted
      several exons, mistakenly generating a single long polypeptide chain. In fact, 3
      consecutive genes exist, the translated versions of which are homologous to
      individual vertebrate fibrinogen chains. The circulating form is likely a 6-chain
      covalent dimer, just as occurs in vertebrates.

PMID- 21860217
TI  - Importance of Toll-like receptor 9 in host defense against M1T1 group A
      Streptococcus infections.
AB  - Timely recognition and elimination of invasive group A Streptococcus (GAS) by
      innate immunity is crucial to control infection. The intracellular pattern
      recognition receptor Toll-like receptor 9 (TLR9) promotes macrophage hypoxia
      inducible factor-1alpha levels, oxidative burst and nitric oxide production in
      response to GAS. TLR9 contributes to GAS clearance in vivo in both localized
      cutaneous and systemic infection models.

PMID- 21860219
TI  - Integrated brain diversification along the early neuraxes.
AB  - Brains develop under the influence of signaling centers that link major
      dorsal/ventral (DV) and anterior/posterior (AP) axes. Over ontogeny, these
      'developmental neuraxes' progress from near global signaling gradients into more
      localized gene expression domains separated by molecular boundaries. Therefore,
      developmental changes along a neuraxis can have major consequences across the
      brain, or more precise effects on a specific structure, depending upon the time
      during ontogeny in which change occurs. It is well known from mammalian systems
      how evolution has acted later in development, via differential neurogenesis, to
      reshape the cortex. Recent studies in fishes show how early changes in DV and AP
      patterning result in divergence of integrated brain regions that ultimately
      define visual versus olfactory ecotypes. We explore the generality of this trend
      and suggest that such early developmental differences integrating brain
      diversification along the neuraxes may be a common theme in vertebrates. Early
      differences in brain patterning among species imply that adult variation in
      sensory function and behavior manifests in the embryo.

PMID- 21860220
TI  - Evo-devo and brain scaling: candidate developmental mechanisms for variation and
      constancy in vertebrate brain evolution.
AB  - Biologists have long been interested in both the regularities and the deviations
      in the relationship between brain, development, ecology, and behavior between
      taxa. We first examine some basic information about the observed ranges of
      fundamental changes in developmental parameters (i.e. neurogenesis timing, cell
      cycle rates, and gene expression patterns) between taxa. Next, we review what is
      known about the relative importance of different kinds of developmental
      mechanisms in producing brain change, focusing on mechanisms of segmentation,
      local and general features of neurogenesis, and cell cycle kinetics. We suggest
      that a limited set of developmental alterations of the vertebrate nervous system
      typically occur and that each kind of developmental change may entail unique
      anatomical, functional, and behavioral consequences for the organism. Thus,
      neuroecologists who posit a direct mapping of brain size to behavior should
      consider that not any change in brain anatomy is possible.

PMID- 21860221
TI  - Pulmonary haptoglobin and CD163 are functional immunoregulatory elements in the
      human lung.
AB  - BACKGROUND: The acute-phase protein haptoglobin (Hp) and its receptor CD163 serve
      as immunomodulators and possess anti-inflammatory besides antioxidant functions.
      OBJECTIVES: To further understand the role of the recently described pulmonary Hp
      (pHp) and its receptor CD163 in case of inflammation and infection, pHp and CD163
      were investigated on mRNA and protein level to gain insight into the cellular
      events taking place upon stimulation with the inflammatory mediators LPS, Pam3,
      cytokine IL-6 and dexamethasone, and upon infection with respiratory pathogens
      (Haemophilus influenzae, Streptococcuspneumoniae and Chlamydia pneumoniae) by use
      of a human ex vivo tissue culture model and cell cultures of A549 and alveolar
      epithelial cells type II. In addition, pHp and CD163 expression in COPD and
      sarcoidosis was assessed. METHODS: We conducted experiments using 942 ex vivo
      cultured lung samples applying immunohistochemistry, immunocytochemistry, in situ
      hybridization, immunofluorescence, real-time PCR, RT-PCR, slot and Western
      immunoblot analyses with tissue lysates and culture supernatants as well as ELISA
      and cytometric bead array analyses. RESULTS: This study describes for the first
      time the expression, regulation and secretion of pHp and its receptor CD163 in
      the human lung. The release of soluble mediators from A549 cell line and human
      monocyte-derived macrophages was observed indicating that Hp differentially
      activates the release of soluble mediators and major chemoattractants.
      CONCLUSIONS: The findings indicate a native function of pHp and CD163 as
      functional pulmonary defense elements due to local expression, regulation and
      secretion during lung infection and as part of the inflammatory immune response
      of the respiratory system.

PMID- 21860222
TI  - Acute exacerbation of idiopathic pulmonary fibrosis: outcome and prognostic
      factors.
AB  - BACKGROUND: Acute exacerbation is a substantial cause of death in patients with
      idiopathic pulmonary fibrosis with poorly described prognostic factors.
      OBJECTIVES: To review the features associated with acute exacerbation of
      idiopathic pulmonary fibrosis and assess its prognostic factors. METHODS: Thirty
      seven occurrences of acute exacerbation of idiopathic pulmonary fibrosis were
      retrospectively reviewed in the medical records of 27 patients. Clinical
      presentation, radiographic studies, pulmonary function tests, laboratory data,
      treatment, and outcome were analyzed. RESULTS: Acute exacerbation of idiopathic
      pulmonary fibrosis occurred more frequently between December and May (75.7%) than
      between June and November (24.3%) (p = 0.01). In-hospital mortality was 27% and
      median survival was 4.2 months (range 0.2-36.6). Significant differences between
      nonsurvivors and survivors included the time elapsed between their admission and
      the initiation of treatment for acute exacerbation (6 vs. 3.1 days, p = 0.04),
      lactate dehydrogenase levels at admission (801 vs. 544.6 IU/l, p = 0.002),
      impairment of the prior forced vital capacity (51.2 vs. 65%, p = 0.01) and
      diffusing capacity for carbon monoxide (21.7 vs. 34%, p = 0.01). Furthermore, the
      evolution of gas exchange in the first 10 days after the initiation of treatment
      was associated with in-hospital and long-term mortality. CONCLUSIONS: Acute
      exacerbations of idiopathic pulmonary fibrosis are more frequent during winter
      and spring. The time between admission and initiation of treatment is a new
      reported prognostic factor that should be investigated further. This finding
      highlights the need for a fast diagnostic approach that should probably be
      standardized. Early gas exchange modifications reflect the response to treatment
      and predict the prognosis.

PMID- 21860223
TI  - Constitutional advancement of growth is associated with early puberty in girls.
AB  - BACKGROUND: Constitutional advancement of growth (CAG) is the growth pattern of
      early growth acceleration that has been shown to be characteristic in girls with
      idiopathic precocious puberty (IPP). The aim of this study was to examine the
      growth pattern of girls with early puberty compared to girls with IPP. METHODS:
      We studied the growth pattern, from birth to presentation, of 61 girls with early
      puberty, of 40 girls with IPP and of 100 healthy girls with normal pubertal onset
      that served as controls. RESULTS: Height SDS (HSDS) at presentation was
      significantly different among the 3 groups (p < 0.001). Girls with early puberty
      were shorter than girls with IPP (HSDS 0.63 +/- 1.09 vs. 0.98 +/- 0.95,
      respectively, p < 0.001) and taller than control girls (HSDS 0.05 +/- 0.94, p <
      0.05). By comparing the linear growth pattern from birth to presentation,
      pairwise comparisons showed that it differed significantly between early puberty
      and control (p < 0.001) as well as between IPP and control girls (p < 0.001),
      whereas the difference between girls with IPP and early puberty was not
      significant (p = 0.09). CONCLUSION: Girls with early puberty present the pattern
      of CAG suggesting that IPP lies at the extreme of the distribution of the normal
      timing of puberty onset.

PMID- 21860224
TI  - Contribution of genoarchitecture to understanding forebrain evolution and
      development, with particular emphasis on the amygdala.
AB  - The amygdala is a forebrain center involved in functions and behaviors that are
      critical for survival (such as control of the neuroendocrine system and
      homeostasis, and reproduction and fear/escape responses) and in cognitive
      functions such as attention and emotional learning. In mammals, the amygdala is
      highly complex, with multiple subdivisions, neuronal subtypes, and connections,
      making it very difficult to understand its functional organization and
      evolutionary origin. Since evolution is the consequence of changes that occurred
      in development, herein we review developmental data based on genoarchitecture and
      fate mapping in mammals (in the mouse model) and other vertebrates in order to
      identify its basic components and embryonic origin in different species and
      understand how they changed in evolution. In all tetrapods studied, the amygdala
      includes at least 4 components: (1) a ventral pallial part, characterized by
      expression of Lhx2 and Lhx9, that includes part of the basal amygdalar complex in
      mammals and a caudal part of the dorsal ventricular ridge in sauropsids and also
      produces a cell subpopulation of the medial amygdala; (2) a striatal part,
      characterized by expression of Pax6 and/or Islet1, which includes the central
      amygdala in different species; (3) a pallidal part, characterized by expression
      of Nkx2.1 and, in amniotes, Lhx6, which includes part of the medial amygdala, and
      (4) a hypothalamic part (derived from the supraoptoparaventricular domain or
      SPV), characterized by Otp and/or Lhx5 expression, which produces an important
      subpopulation of cells of the medial extended amygdala (medial amygdala and/or
      medial bed nucleus of the stria terminalis). Importantly, the size of the SPV
      domain increases upon reduction or lack of Nkx2.1 function in the hypothalamus.
      It appears that Nkx2.1 expression was downregulated in the alar hypothalamus
      during evolution to mammals, which may have produced an enlargement of SPV and
      the amygdalar cell subpopulation derived from it.

PMID- 21860225
TI  - Repetitive DNA and meiotic behavior of sex chromosomes in Gymnotus pantanal
      (Gymnotiformes, Gymnotidae).
AB  - Neotropical fishes have a low rate of chromosome differentiation between sexes.
      The present study characterizes the first meiotic analysis of sex chromosomes in
      the order Gymnotiformes. Gymnotus pantanal - females had 40 chromosomes (14m/sm,
      26st/a) and males had 39 chromosomes (15m/sm, 24st/a), with a fundamental number
      of 54 - showed a multiple sexual determination chromosome system of the type
      X(1)X(1)X(2)X(2)/X(1)X(2)Y. The heterochromatin is restricted to centromeres of
      all chromosomes of the karyotype. The meiotic behavior of sex chromosomes
      involved in this system in males is from a trivalent totally pared in the
      pachytene stage, with a high degree of similarity. The cells of metaphase II
      exhibit 19 and 20 chromosomes, normal disjunction of sex chromosomes and the
      formation of balanced gametes with 18 + Y and 18 + X(1)X(2) chromosomes,
      respectively. The small amount of heterochromatin and repetitive DNA involved in
      this system and the high degree of chromosome similarity indicated a recent
      origin of the X(1)X(1)X(2)X(2)/X(1)X(2)Y system in G. pantanal and suggests the
      existence of a simple ancestral system with morphologically undifferentiated
      chromosomes.

PMID- 21860226
TI  - Comparison of the proliferation, viability, and differentiation capacity of
      adipose-derived stem cells from different anatomic sites in rabbits.
AB  - Tissue engineering is clinically promising for missing and damaged tissues.
      Adipose-derived stem cells (ASCs), a type of mesenchymal stem cells, represent a
      reliable source of seed cells for tissue engineering with multiple merits such as
      minimal invasion, abundant yield, little immunity, low morbidity, easy isolation,
      and rapid expansion. However, because the properties of adipose tissue-derived
      cells differ depending on the fat depot from which they are derived, we compared
      the ASCs from three anatomic sites of New Zealand white rabbits: subcutaneous
      inguinal (SI), subcutaneous dorsocervical (SD), and retroperitoneal perinephric
      (RP) regions. We investigated cellular behaviors including proliferation,
      viability, and differentiation. The ASCs of the subcutaneous regions (SI and SD)
      had higher performances in all assessments compared to those of the RP region.
      Moreover, the SI and SD ASCs had significant differences, with SI ASCs having
      better properties than SD ASCs. We conclude that the different anatomic
      distributions of fat contribute to the different behaviors of ASCs. The SI region
      offers the most applicable cell source reservoir for ASC tissue engineering.

PMID- 21860227
TI  - Candida albicans-induced chronic thrombocytopenic purpura.
AB  - We present 2 patients with chronic immune thrombocytopenic purpura (ITP)
      secondary to Candida albicans infection. Neither patient responded to standard
      ITP therapy including splenectomy. Appropriate antifungal treatment of the C.
      albicans infection was followed by sustained improvement in platelet count in
      both patients. To our knowledge, this is the first report of ITP in association
      with C. albicans infection.

PMID- 21860229
TI  - Intratympanic steroid therapy using the Silverstein MicrowickTM for refractory
      sudden sensorineural hearing loss increases speech intelligibility.
AB  - OBJECTIVE: To determine whether delivery of methylprednisolone to the round
      window (administered for 10 days after the onset of the hearing loss) can improve
      hearing and, in particular, speech intelligibility, after the failure of
      conventional treatment for idiopathic sudden sensorineural hearing loss. RESULTS:
      Of the 26 patients enrolled in this non-randomized retrospective study, 14
      patients (54%) showed an improvement in the pure tone average (PTA) and 12
      remained unchanged. The topical steroid therapy brought about an overall
      improvement in PTA of 13.5 +/- 7.3 dB for the 26 patients enrolled. The auditory
      capacity index, defined as the mean speech discrimination score obtained at 40,
      55 and 70 dB, improved by 24.2 +/- 8.7% in 26 patients. Among the 12 patients
      with a stable PTA, 9 showed an increase in speech intelligibility. CONCLUSION:
      Local administration of steroids to the inner ear through the round window route
      improves hearing and speech intelligibility in patients after failure of
      conventional therapy.

PMID- 21860228
TI  - Chronic kidney disease and risk of death from infection.
AB  - BACKGROUND: Infection, bacteremia and sepsis are major sources of morbidity and
      mortality in patients with end-stage renal disease. This study sought to
      determine the association between predialysis chronic kidney disease (CKD) and
      infection-related mortality. METHODS: We analyzed participants in the Third
      National Health and Nutrition Examination Survey (NHANES III). The study included
      adults >=45- years-old without end-stage renal disease. Estimated glomerular
      filtration rate (eGFR) was categorized as >=60, 45-59.9 and <45 ml/min per 1.73
      m(2), and urinary albumin-to-creatinine ratio (ACR) as <30, 30-299.9 and >=300
      mg/g. The study identified infection-related mortality, including septicemia,
      respiratory, abdominal and gastrointestinal, cardiac, kidney and genitourinary,
      neurologic, and other infections over a median of 13 years using the National
      Death Index. RESULTS: Of 7,400 participants included in the study, 206 died from
      infections. Compared to individuals with eGFR >=60 ml/min per 1.73 m(2),
      infection-related mortality was higher for those with lower eGFR [adjusted HR =
      1.36 (95% CI: 0.81, 2.30) and 2.36 (1.04, 5.38) for eGFR of 45-59.9 and <45
      ml/min per 1.73 m(2), respectively; p trend = 0.06]. Compared to individuals with
      ACR <30 mg/g, infection-related mortality was higher for ACR levels of 30-299 and
      >=300 mg/g [adjusted HR = 1.68 (95% CI: 0.97, 2.92) and 2.84 (0.92, 8.74), p
      trend = 0.02]. CONCLUSIONS: Reduced eGFR and albuminuria are associated with
      increased risk for infection-related mortality. Efforts are needed to reduce its
      incidence and mitigate the effects of infections among individuals with CKD.

PMID- 21860230
TI  - Localization of calbindin-d28k and calretinin in the brain of dermophis mexicanus
      (amphibia: gymnophiona) and its bearing on the interpretation of newly recognized
      neuroanatomical regions.
AB  - The analysis of the distribution of the calbindin-D28k and calretinin
      immunoreactive (CBir and CRir) systems recently described in the brain of anuran
      and urodele amphibians was very useful for the interpretation of many otherwise
      indistinct brain regions and cell masses. In the present study we have followed a
      similar approach to investigate the distribution of CBir and CRir cell bodies and
      fibers in the brain of Dermophis mexicanus, a member of the much neglected third
      amphibian order of gymnophionans. The pattern of distribution obtained showed
      particular characteristics in Dermophis, such as the existence of abundant CRir
      elements in the olfactory bulbs and CBir and CRir cell populations in pallial
      areas. The distinct distribution of the two proteins allowed the tentative
      identification of currently described subregions, mainly in the amygdaloid
      complex and hypothalamic areas. The analysis of the diencephalon and brainstem
      distribution framed in the neuromeric model highlighted common traits with other
      amphibians but also specific features. Therefore, the immunohistochemical
      detection of calcium-binding proteins has served to discern cell populations and
      has helped to demonstrate neuronal heterogeneity. However, it should be pointed
      out that a straightforward comparison based only on the presence of these
      proteins should not be made due to the great variability observed in well
      established homologous regions in the brain of different vertebrates, as
      evidenced within the class Amphibia.

PMID- 21860231
TI  - Septic acute kidney injury: the culprit is inflammatory apoptosis rather than
      ischemic necrosis.
AB  - For a long time, acute kidney injury (AKI) was considered to be a primarily
      hemodynamic condition characterized by a reduction of renal blood flow, induced
      by either cardiogenic or distributive (septic) shock. Consequently, all efforts
      to treat AKI were essentially concentrated on increasing renal flow by enhancing
      cardiac flow output and perfusion pressure. At the beginning of this decade,
      Bellomo and co-workers produced new and intriguing data in an animal model of
      septic AKI that undermined existing concepts. They observed that medullar and
      cortical renal blood flow were both maintained and even increased in septic
      shock, underscoring that septic AKI was a totally different physiological
      phenomenon than nonseptic AKI. Also, apoptosis was found to play a more important
      role in sepsis and septic shock than pure necrosis. Despite these findings, the
      role of apoptosis as a main mechanism of organ dysfunction remains topic of
      debate.

PMID- 21860232
TI  - Determination of dialysis dose: a clinical comparison of methods.
AB  - BACKGROUND: Guidelines recommend regular measurements of the delivered
      hemodialysis dose Kt/V. Nowadays, automatic non-invasive online measurements are
      available as alternatives to the conventional method with blood sampling,
      laboratory analysis, and calculation. METHODS: In a prospective clinical trial,
      three different methods determining dialysis dose were simultaneously applied:
      Kt/V(Dau) (conventional method with Daugirdas' formula), Kt/V(OCM) [online
      clearance measurement (OCM) with urea distribution volume V based on
      anthropometric estimate], and Kt/V(BCM) [OCM measurement with V measured by
      bioimpedance analysis (Body Composition Monitor)]. RESULTS: 1,076 hemodialysis
      patients were analyzed. The dialysis dose was measured as Kt/V(Dau) = 1.74 +/-
      0.45, Kt/V(OCM) = 1.47 +/- 0.34, and Kt/V(BCM) = 1.65 +/- 0.42. The difference
      between Kt/V(OCM) and Kt/V(BCM) was due to the difference between anthropometric
      estimated V(Watson) and measured V(BCM). Compared to Kt/V(Dau), Kt/V(OCM) was 15%
      lower and Kt/V(BCM) 5% lower. Kt/V(Dau) was incidentally prone to falsely high
      values due to operative errors, whereas in these cases OCM-based measurements
      Kt/V(OCM) and Kt/V(BCM) delivered realistic values. CONCLUSIONS: The automated
      OCM Kt/V(OCM) with anthropometric estimation of urea distribution volume was the
      easiest method to use, but Kt/V(BCM) with measured urea distribution volume was
      closer to the conventional method.

PMID- 21860233
TI  - Clinical outcome after mechanical recanalization as mono- or adjunctive therapy
      in acute stroke: importance of time to recanalization.
AB  - BACKGROUND: The clinical benefit of mechanical recanalization procedures for
      acute stroke is still a matter of debate. We report the clinical and imaging
      results of 34 consecutive patients, focusing on time aspects (i.e. vessel
      occlusion time and procedure duration). METHODS: During a 3-year period, 34
      stroke patients with large-vessel occlusion (anterior circulation, n = 19;
      posterior circulation, n = 15) were treated with several mechanical
      recanalization devices with (n = 17) or without prior intravenous thrombolysis.
      Clinical and imaging data before (NIHSS) and after treatment [(mRS) 3 and 6-30
      months] were analyzed. The angiographic outcome (TIMI score), complication rates,
      and procedural issues (i.e. procedure duration and vessel occlusion time) were
      assessed. RESULTS: The median NIHSS on admission was 17. Successful
      recanalization (TIMI 2 and 3) was achieved in 23 (68%) patients. The median time
      from symptom onset to recanalization was 330 min, and the median time from
      angiography to recanalization was 101 min. Six (18%) patients had a good clinical
      outcome (3-month mRS <=2), and 10 (29%) died. The vessel occlusion time was
      significantly shorter in patients with a good compared to poor clinical outcome
      (247 vs. 348 min, p = 0.024). In the subgroup of anterior circulation stroke,
      successful recanalization, and no symptomatic intracranial hemorrhage (n = 11),
      there was a strong correlation between vessel occlusion time and clinical outcome
      (r = 0.711, p = 0.014). CONCLUSIONS: The rate of vessel recanalization with
      endovascular therapy is promising. Nevertheless, the long-term clinical outcome
      is still disadvantageous in the majority of patients, presumably due to too long
      vessel occlusion times. Better strategies for patient selection and optimization
      of recanalization strategies (i.e. shorter time intervals to vessel patency) are
      warranted.

PMID- 21860235
TI  - Does perfusion computed tomography facilitate clinical decision making for
      thrombolysis in unselected acute patients with suspected ischaemic stroke?
AB  - BACKGROUND: Despite use in clinical practice and major positive trials of
      thrombolysis, non-contrast computed tomography (NCCT) is not sensitive for
      identifying penumbral tissue in acute stroke. This study evaluated how
      physiological imaging using CT perfusion (CTP) could add to the diagnostic
      utility of an NCCT and inform clinical decisions regarding thrombolysis. METHODS:
      Forty imaging datasets containing NCCT and CTP were retrospectively identified
      from a cohort of consecutive acute stroke patients. Two sets of observers (n = 6)
      and a neuroradiologist evaluated the images without knowledge of clinical
      symptoms. Inter-observer agreement was calculated using the kappa statistic for
      identifying acute ischaemic change on NCCT: perfusion abnormalities (namely
      cerebral blood volume, cerebral blood flow and time to peak), and penumbral
      tissue on perfusion maps obtained by two image processing algorithms. RESULTS:
      Inter-rater agreement was moderate (kappa = 0.54) for early ischaemic change on
      NCCT. Perfusion maps improved this to substantial for cerebral blood volume
      (kappa = 0.67) and to almost perfect for time to peak (kappa = 0.87) and cerebral
      blood flow (kappa = 0.87). The agreement for qualitative assessment of penumbral
      tissue was substantial to perfect for images obtained using the two different
      perfusion algorithms. Overall, there was a high rate of decision to thrombolyse
      based on NCCT (81.25%). CTP strengthened the decision to thrombolyse based on
      NCCT in 38.3% of cases. It negatively influenced the decision in 14.6% of cases,
      this being significantly more common in experienced observers (p = 0.02).
      CONCLUSIONS: We demonstrate that the qualitative evaluation of CTP produces near
      perfect inter-observer agreement, regardless of the post-processing method used.
      CTP is a reliable, accessible and practical imaging modality that improves
      confidence in reaching the appropriate diagnosis. It is particularly useful for
      less experienced clinicians, to arrive at a physiologically informed treatment
      decision.

PMID- 21860234
TI  - Retrospective nationwide survey of acute stroke due to large vessel occlusion in
      Japan: a review of 1,963 patients and the impact of endovascular treatment.
AB  - BACKGROUND: The purpose of this study was to clarify the clinical impact of
      endovascular treatment (EVT) on acute cerebral large vessel occlusion using a
      nationwide survey of Japan conducted in 2009. METHODS: Patients admitted within
      24 h after stroke onset were registered retrospectively. Treatment selection,
      methods, and clinical results were analyzed. RESULTS: A total of 1,963 patients
      (855 women, 1,108 men) treated in 2008 were registered from 68 medical centers in
      Japan. Mean age on admission was 74.1 +/- 12.2 years (range 7-100 years). The
      first treatment was conservative therapy in 68%, intravenous tissue plasminogen
      activator (IV-tPA) in 21%, EVT in 9%, and combined IV-tPA + EVT in 2%. EVT mainly
      comprised angioplasty, intra-arterial thrombolysis and/or the combination of
      both. Patients treated <=3 h after onset (1,286 cases) showed better clinical
      outcomes with combined IV-tPA + EVT than with conservative therapy, and
      significant differences in outcomes were seen for patients with occlusion of the
      basilar artery (p < 0.01) or middle cerebral artery (p < 0.01), but not the
      internal carotid artery. At >3 h after onset (677 patients), no IV-tPA was
      performed, and EVT was performed in 11%. Among the patients treated by EVT, there
      were significant differences in clinical outcome between complete recanalization
      (TIMI grade 3) and partial/no recanalization (TIMI grade 0-2) (p < 0.001; OR
      5.98; 95% CI 3.27-10.96) and between any recanalization (TIMI grade 1-3) and no
      recanalization (TIMI grade 0) (p < 0.001; OR 36.15; 95% CI 4.88-267.53).
      CONCLUSIONS: This nationwide survey showed the efficacy of EVT with IV-tPA in
      patients with occlusion of the basilar or middle cerebral artery, but not of the
      internal carotid artery. The effects of new endovascular devices should be
      clarified in the near future.

PMID- 21860236
TI  - Cholesterol levels and risk of hemorrhagic transformation after acute ischemic
      stroke.
AB  - BACKGROUND: The association between cholesterol levels and hemorrhagic
      transformation (HT) is still controversial. Studies investigating this issue are
      influenced by treatments as some are characterized by a higher risk of HT. The
      aim of our study was to evaluate, in a hospital-based series of patients not
      treated with thrombolysis, the relationship between cholesterol levels and HT.
      METHODS: We retrospectively collected information about total cholesterol (TC)
      and low-density lipoprotein cholesterol (LDLC) levels at admission in a
      consecutive series of 240 patients with anterior ischemic stroke (IS). The TC and
      LDLC levels were arranged in 3 groups according to their percentile distribution.
      RESULTS: TC levels were available for 215 patients (89.6%), while LDLC levels
      were available for 184 patients (76.7%). The risk of HT significantly increased
      with decreasing levels of TC (p for trend = 0.03) and LDLC (p for trend = 0.01).
      In multivariate analysis, the risk of HT was significantly higher in the groups
      of patients with the lowest TC (OR 2.8, 95% CI 1.0-8.9, p = 0.05) and LDLC (OR
      5.0, 95% CI 1.2-20.1, p = 0.002) values compared to those with the highest ones.
      CONCLUSION: We confirm that lower TC and lower LDLC levels are associated with an
      increased risk of HT. As none of our patients received thrombolytic therapy, the
      results of our study provide baseline information about the natural history of
      HT.

PMID- 21860237
TI  - Hyperdense middle cerebral and/or internal carotid arteries in acute ischemic
      stroke: rate, predictive factors and influence on clinical outcome.
AB  - BACKGROUND: In patients with acute stroke, the hyperdense middle cerebral artery
      (MCA) and internal carotid artery (ICA) signs on CT scans are markers of early
      ischemia, but their prognostic implications remain unclear.The aims of this
      prospective study were to assess: (1) the occurrence rate of hyperdense MCA
      and/or ICA in patients admitted for acute ischemic stroke; (2) the risk factors
      for hyperdense MCA and/or ICA; (3) the correlation between hyperdense MCA and/or
      ICA and functional outcome at 3 months. METHODS: Consecutive patients admitted
      with ischemic stroke between 1 January 2006 and 30 June 2010 were included in
      this prospective single-centre cohort study. RESULTS: 1,010 patients (mean age
      71.9 years; 56.7% males) were included in the study. Among these patients, 148
      (14.7%; mean age 71.2 years; 52% males) had hyperdense MCA and/or ICA. Overall,
      163 patients (16.1%) had a final infarct covering more than one third of the MCA
      territory. Seventy-eight of 148 patients (52.7%) with hyperdense MCA and/or ICA
      had an infarct involving more than one third of the MCA territory compared to 85
      of the 862 patients without artery hyperdensity (9.9%). At 3 months, 18 patients
      were lost to follow-up, 325 patients (32.8%) were disabled and 165 died (16.5%).
      Age (OR 1.06 for 1 added year; 95% CI 1.04-1.08), National Institute of Health
      Stroke Scale score for 1 added point on admission (OR 1.2; 95% CI 1.2-1.3),
      stroke due to atherosclerosis (OR 2.3; 95% CI 1.0-5.4), hemorrhagic
      transformation of the ischemic lesion (OR 2.2; 95% CI 1.0-4.9), and hyperdense
      MCA and/or ICA (OR 2.0; 95% CI 1.0-4.0) were associated with adverse outcome.
      CONCLUSIONS: In this prospective cohort of patients with acute ischemic stroke,
      we observed an incidence of hyperdense MCA and/or ICA arteries of about 15%;
      hyperdense MCA and/or ICA were associated with a final infarct involving more
      than one third of the MCA territory and poor functional outcome at 3 months.

PMID- 21860238
TI  - Temporal distribution and magnitude of the vulnerability period around stroke
      depend on stroke subtype.
AB  - BACKGROUND: We aimed to analyze the rate and time distribution of pre- and post
      morbid cerebrovascular events in a single ischemic stroke population, and whether
      these depend on the etiology of the index stroke. METHODS: In 2,203 consecutive
      patients admitted to a single stroke center registry (ASTRAL), the ischemic
      stroke that led to admission was considered the index event. Frequency
      distribution and cumulative relative distribution graphs of the most recent and
      first recurrent event (ischemic stroke, transient ischemic attack, intracranial
      or subarachnoid hemorrhage) were drawn in weekly and daily intervals for all
      strokes and for all stroke types. RESULTS: The frequency of events at identical
      time points before and after the index stroke was mostly reduced in the first
      week after (vs. before) stroke (1.0 vs. 4.2%, p < 0.001) and the first month (2.7
      vs. 7.4%, p < 0.001), and then ebbed over the first year (8.4 vs. 13.1%, p <
      0.001). On daily basis, the peak frequency was noticed at day -1 (1.6%) with a
      reduction to 0.7% on the index day and 0.17% 24 h after. The event rate in
      patients with atherosclerotic stroke was particularly high around the index
      event, but 1-year cumulative recurrence rate was similar in all stroke types.
      CONCLUSIONS: We confirm a short window of increased vulnerability in ischemic
      stroke and show a 4-, 3- and 2-fold reduction in post-stroke events at 1 week, 1
      month and 1 year, respectively, compared to identical pre-stroke periods. This
      break in the 'stroke wave' is particularly striking after atherosclerotic and
      lacunar strokes.

PMID- 21860240
TI  - Activity of matrix metalloproteinases in bovine versus human dentine.
AB  - Metalloproteinases (MMPs) have been implicated with metabolism of collagen in
      physiological and pathological processes in human dentine. As bovine teeth have
      been used as a substitute for human teeth in laboratory analysis, this study
      evaluated the activity of MMP-2 and -9 in bovine versus human dentine. Bovine and
      human dentine fragments, from crowns and roots, were powderized. Protein
      extraction was performed by two protocols: a neutral extraction with guanidine
      HCl/EDTA (pH 7.4) and an acidic extraction with citric acid (pH 2.3).
      Gelatinolytic activities of extracts were revealed by zymography. MMP-2 and -9
      were detected in crown and root dentine from bovine and human teeth. Total
      activities of MMP-2 were 11.4 +/- 2.2, 14.6 +/- 2.0, 9.7 +/- 1.2 and 12.4 +/- 0.9
      ng/ml for bovine root, human root, bovine crown and human crown dentine,
      respectively. Corresponding activities for MMP-9 were 14.9 +/- 2.0, 15.3 +/- 1.3,
      15.4 +/- 1.3 and 15.5 +/- 1.3 ng/ml, respectively. Bovine dentine was found to be
      a reliable substrate for studies involving the activity of MMP-2 and -9.

PMID- 21860239
TI  - Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse:
      targeted elimination of Streptococcus mutans and prevention of demineralization.
AB  - BACKGROUND/AIMS: Streptococcus mutans, the major etiological agent of dental
      caries, has a measurable impact on domestic and global health care costs. Though
      persistent in the oral cavity despite conventional oral hygiene, S. mutans can be
      excluded from intact oral biofilms through competitive exclusion by other
      microorganisms. This suggests that therapies capable of selectively eliminating
      S. mutans while limiting the damage to the normal oral flora might be effective
      long-term interventions to fight cariogenesis. To meet this challenge, we
      designed C16G2, a novel synthetic specifically targeted antimicrobial peptide
      with specificity for S. mutans. C16G2 consists of a S. mutans-selective
      'targeting region' comprised of a fragment from S. mutans competence stimulation
      peptide (CSP) conjoined to a 'killing region' consisting of a broad-spectrum
      antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust
      efficacy and selectivity for S. mutans, and not other oral bacteria, and affects
      targeted bacteria within seconds of contact. METHODS: In the present study, we
      evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study
      to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral
      remineralization/demineralization model. RESULTS AND CONCLUSIONS: C16G2 rinse
      usage was associated with reductions in plaque and salivary S. mutans, lactic
      acid production, and enamel demineralization. The impact on total plaque bacteria
      was minimal. These results suggest that C16G2 is effective against S. mutans in
      vivo and should be evaluated further in the clinic.

PMID- 21860241
TI  - Prevalence and severity of clinical consequences of untreated dentine carious
      lesions in children from a deprived area of Brazil.
AB  - Disadvantaged children suffer because tooth cavities are not being treated and
      their clinical consequences not being surveyed. The present study aimed to assess
      the prevalence and severity of clinical consequences of untreated dentine carious
      lesions in schoolchildren from a deprived area of Brazil and to investigate the
      determinants of the pufa index. A sample of 835 children aged 6-7 years, from six
      public schools, was examined by 3 calibrated examiners. Clinical consequences of
      untreated dentine carious lesions in primary teeth were diagnosed using the four
      codes of the pufa index: 'p' (pulpal involvement), 'u' (ulceration), 'f'
      (fistulae), 'a' (abscess). Effects of gender, age, school, history of extraction,
      and toothache on the prevalence of pufa codes were tested. The prevalence of pufa
      codes was 23.7%. The mean pufa score was 0.4 +/- 0.9. Code 'p' was the most
      prevalent (19.5%), whereas code 'u' was least prevalent (0.1%). Children with a
      history of extracted primary teeth due to caries had a 2.7 times higher chance to
      have a pufa code than children with no previous extraction. Children with
      toothache had a 5.6 times higher chance to have a pufa code than children without
      toothache. The prevalence of clinical consequences of untreated dentine carious
      lesions was moderate and the severity was low. The pufa index is an
      epidemiological tool complementary to existing caries indices aimed to assess
      dental caries. However, there appears to be no need to include code 'u' nor to
      score codes 'f' and 'a' separately.

PMID- 21860243
TI  - Effect of low-dose gemcitabine on unresectable pancreatic cancer in elderly
      patients.
AB  - BACKGROUND/AIMS: The efficacy of gemcitabine (GEM) on unresectable pancreatic
      cancer has been reported. However, in elderly patients, severe toxicities are
      frequently observed. In this study we aimed to assess the efficacy of low-dose
      GEM on unresectable pancreatic cancer in elderly patients. METHODS: We reviewed
      68 elderly patients (>=65 years) with unresectable pancreatic cancer. Thirty-six
      patients were treated with low-dose GEM (600-800 mg/m(2); GEM group), and the
      other 32 received best supportive care (BSC group). RESULTS: Median survival was
      7.6 and 2.3 months in the GEM and BSC groups, respectively. In the GEM group, the
      median survival period was longer in 24 patients showing partial response or
      stable disease than in 12 patients showing progressive disease (11.4 vs. 5.3
      months). Furthermore, the patients showing progressive disease had better 6-month
      survival than patients in the BSC group. Thirteen patients (36%) developed severe
      toxicities (grade 3 or 4). Low-dose GEM, stage of disease and performance status
      were associated with the prognosis. CONCLUSIONS: Low-dose GEM may improve the
      prognosis of elderly patients with unresectable pancreatic cancer. Furthermore,
      frequencies of severe toxicity seem lower in patients treated with low-dose GEM
      compared with previous reports.

PMID- 21860242
TI  - Biomimetic approach for root caries prevention using a proanthocyanidin-rich
      agent.
AB  - The aim of this study was to evaluate the effects of a proanthocyanidin-rich
      grape seed extract (GSE) on the in vitro demineralization of root dentine. Root
      fragments were obtained from sound human teeth. The fragments were randomly
      assigned to different treatments solutions: GSE, fluoride (F), GSE+F and
      distilled water (control). Samples were treated daily for 30 min and subjected to
      a pH cycling artificial caries protocol using demineralization cycles (2.2 mM
      CaCl(2)*H(2)O, 2.2 mM KH(2)PO(4), 50 mM acetic acid, pH 4.3) for 6 h and
      remineralization cycles (20 mM HEPES, 2.25 mM CaCl(2)*H(2)O, 1.35 mM KH(2)PO(4),
      130 mM KCl, pH 7.0) for 17.5 h. Mineral loss (DeltaZ) and lesion depth (LD) were
      determined after 18 days of treatment/pH cycling, by transverse microradiography.
      GSE was able to minimize DeltaZ and LD compared with the control group (p <
      0.0001). The GSE+F and F groups showed the lowest values of DeltaZ and LD (p <
      0.05), with no statistically significant differences between them (p = 0.554 and
      p = 0.726, respectively). A biomimetic approach to strengthen root dentine using
      GSE results in decreased rates of root demineralization and may be used in
      conjunction with F to prevent root caries.

PMID- 21860245
TI  - The discovery of pathogen recognition receptors (PRR).

PMID- 21860246
TI  - Introducing nutritional genomics teaching in undergraduate dietetic curricula.
AB  - Nutritional genomics offers great promise to personal health management based on
      the understanding of the relationship between diet, gene expression and health
      outcomes. Our readiness to deliver nutrigenetic-based nutrition education has
      been slow due to the complexity of gene-nutrient interaction and interplays
      between many disciplines such as genetics, nutrition, biostatistics, sociology,
      law and philosophy in the process. To make a public impact, we must prepare
      future allied health professionals with knowledge necessary to provide
      nutrigenetic and nutrigenomic education. We have described here a plan to
      introduce nutrigenetic and nutrigenomic education in dietetic curricula that may
      serve as an example for other allied health programs.

PMID- 21860244
TI  - Khat use and trait anger: effects on affect regulation during an acute stressful
      challenge.
AB  - Khat (Catha edulis) is a widely used stimulating drug often consumed in daily
      routine in Yemen and East African countries. Chewing khat acutely elicits states
      of euphoria and feelings of well-being which later shift into emotional
      instability and low mood. Little is known about emotional regulation in habitual
      khat chewers. In this study, we compared self-reports on trait anger as well as
      positive and negative affect responses to a mental arithmetic challenge.
      Participants included 135 men and women from Yemen who chew khat regularly,
      occasionally or not at all. Participants attended a laboratory session that
      involved resting periods and performing a math challenge. Analyses of variance
      and regression show that regular khat chewing is associated with higher trait
      anger, more pronounced negative responses during stress and less pronounced
      positive emotional states. These results suggest that regular khat chewing is
      associated with disturbances in emotion regulation processes.

PMID- 21860247
TI  - Pre- and postnatal methyl deficiency in the rat differentially alters glucose
      homeostasis.
AB  - BACKGROUND/AIMS: Early-life methyl-donor deficiency is implicated in growth
      restriction and later-life development of type 2 diabetes mellitus. We
      ascertained whether dietary methyl-donor deficiency in the mother during
      pregnancy or during postweaning growth in the rat would impair glucose
      homeostasis, insulin secretion and pancreatic endocrine development in young
      adults. METHODS: Effects of maternal methyl deficiency (90% deficiency in
      methionine, folate and choline) were compared with those of postweaning methyl
      deficiency and with control diets for effects on growth, impaired glucose
      tolerance, insulin secretion and pancreas development in offspring. Studies
      focussed on male offspring, which have been shown more susceptible to early-life
      influences on later disease development. RESULTS: Prenatal methyl deficiency
      delayed delivery, restricted birthweight by 22%, reduced litter size by 33% and
      increased offspring mortality to 23% shortly after birth. It reduced relative
      endocrine pancreatic mass in adult male offspring to 46% of endocrine mass in
      controls, but only mildly impaired their glucose tolerance and insulin secretion.
      In contrast, postweaning methyl deficiency restricted growth of male rats and
      reduced relative pancreatic endocrine mass (-40%), but improved their glucose
      tolerance, despite decreased insulin secretion. CONCLUSION: It is clear that the
      global undernutrition (UN) during pregnancy in rodents alters glucose metabolism
      in adult offspring. It has been hypothesised that alterations in epigenetic
      mechanisms may underlie this phenotype. However, removing all methyl donors
      during pregnancy, which are essential for epigenetic processes in development,
      did not cause any alteration in glucose metabolism in offspring as seen in the
      global UN model.

PMID- 21860248
TI  - Thrombospondin-1 short hairpin RNA suppresses tubulointerstitial fibrosis in the
      kidney of ureteral obstruction by ameliorating peritubular capillary injury.
AB  - BACKGROUND/AIMS: Thrombospondin-1 (TSP-1), a naturally occurring inhibitor of
      angiogenesis, is an important mediator of renal fibrosis in clinical and
      experimental kidney disease. Increasing evidence shows that the microvasculature
      plays a critical role in progressive renal disease. The present study was
      undertaken to investigate whether interstitial fibrosis could be prevented by
      abolishing TSP-1 function in unilateral ureteral obstruction (UUO)-induced renal
      fibrosis. METHODS AND RESULTS: A short hairpin RNA vector, designated Thbs-1,
      significantly suppressed TSP-1 in both transcriptional and translational levels
      in in vitro-cultured cells and in vivo fibrosis-induced mouse kidney.
      Furthermore, TSP-1 RNA interference increased the protein level of vascular
      endothelial growth factor (VEGF) and the density of peritubular capillaries
      (PTCs), reduced the expression of hypoxia-inducible factor-1alpha in
      tubulointerstitial cells, and collagen III and the connective tissue growth
      factor expression were markedly reduced from day 7 after UUO-induced fibrosis,
      but un- or vector-treated mice maintained their expression. TSP-1 shRNA
      suppressed the protein level of TSP-1, increased VEGF expression and PTC density
      and alleviated the development of renal interstitial fibrosis in UUO mice.
      CONCLUSION: These data suggest that inhibition of TSP-1 expression prevented
      tubulointerstitial fibrosis through ameliorating PTC injury.

PMID- 21860249
TI  - Purinergic P2X7 receptors participate in disturbed intracellular calcium
      homeostasis in peripheral blood mononuclear cells of patients with chronic kidney
      disease.
AB  - BACKGROUND: P2X(7) receptors intervene with lymphocyte activation and are
      responsible for multiple processes, including calcium influx. Here, we studied
      the participation of P2X(7) receptors in disturbed intracellular calcium
      homeostasis regulation in early-stage chronic kidney disease (CKD). METHODS: The
      study involved 20 healthy volunteers and 20 CKD stage 2-3 patients. The free
      cytosolic calcium concentration ([Ca(2+)](i)) was measured using fluorimetry. The
      P2X(7) pore function was evaluated by the fluorescent dye ethidium bromide.
      RESULTS: In peripheral blood mononuclear cells (PBMCs) of patients, [Ca(2+)](i),
      intracellular calcium stores and the capacitative calcium entry were increased
      when compared with healthy subjects. The agonist of P2X(7) receptor BzATP caused
      a sustained increase in [Ca(2+)](i) in both groups, but the effect was smaller in
      patients. The antagonist at the P2X(7) receptor KN-62 reduced [Ca(2+)](i) in
      patients, but had no effect in healthy subjects. In patients, the permeability of
      ethidium bromide through P2X(7) pores, as well as through BzATP-activated and KN
      62-inhibited pores, was distinct from permeability in healthy volunteers.
      CONCLUSIONS: These results demonstrate that the calcium signaling pathway in
      PBMCs of CKD patients is defective already in CKD stage 2-3, and the pore-forming
      P2X(7) receptors are involved in these pathophysiological processes.

PMID- 21860251
TI  - Incidence and clinical features of amyotrophic lateral sclerosis in More and
      Romsdal County, Norway.
AB  - BACKGROUND: To determine the annual incidence rate and clinical features of
      amyotrophic lateral sclerosis (ALS) in More and Romsdal County, Norway, in the 20
      year period from 1988 to 2007. METHODS: We recruited ALS patients retrospectively
      from the patient database of the two neurological departments in More and Romsdal
      County, Norway. The patients were identified by use of the international
      classification code for diseases. We recorded gender, age, municipality,
      symptoms, clinical signs, time from onset to diagnosis and death. RESULTS: 105
      patients met the inclusion criteria. The crude annual incidence was 2.17 per
      100,000 for the period 1988-2007. Gender-specific incidence for men was 2.32 per
      100,000, and for women 2.03 per 100,000. Mean age at symptom onset was 66.8 +/-
      10.5 years. Mean interval from onset of symptoms to diagnosis was 13.5 +/- 11.0
      months, and mean survival time from diagnosis was 18.0 +/- 22.0 months.
      Prevalence rate estimated on December 31, 2007 was 4.06 per 100,000. CONCLUSION:
      The present study shows an annual incidence of ALS of similar magnitude to the
      previous studies from the Nordic countries during the past years. The short
      survival time corroborates prior studies, and is stable throughout the two
      studied decades.

PMID- 21860250
TI  - Clinico-pathological conference on acute kidney injury in a patient with
      nephrotic syndrome.

PMID- 21860252
TI  - Estimated prevalence of acoustic cranial windows and intracranial stenosis in the
      US elderly population: ultrasound screening in adults for intracranial disease
      study.
AB  - BACKGROUND: Intracranial atherosclerosis is an important etiology of stroke in
      the USA, but its prevalence in the general population remains unknown. This study
      was performed to determine the feasibility of transcranial Doppler ultrasound
      (TCD) for general population screening and to estimate the prevalence of
      intracranial stenosis in the USA. METHODS: We used a public database to randomly
      select 99 subjects aged 65-84 years residing in a well-defined geographic area.
      For all subjects clinical history was reviewed, blood pressure was recorded and
      TCD examination was performed to identify intracranial stenosis. RESULTS: The
      mean age of subjects was 72 years, 42 were men, and 17 were African-Americans.
      All acoustic windows were present in 77 subjects. After multivariate adjustment,
      the odds of absence of a bone window were higher in African-Americans [odds ratio
      (OR) 6.0, 95% confidence interval (CI) 1.8-2.0], nonsmokers (OR 3.1, 95% CI 1.0
      9) and those with a high BMI (9% higher odds per index point). Among 77 subjects
      who had all acoustic windows present, intracranial stenosis of >50% was
      identified in 6.5%, and intracranial stenosis of any severity was identified in
      16% of the persons. Intracranial stenosis was most prevalent in the middle
      cerebral artery (6%). CONCLUSION: Presence of acoustic windows is associated with
      vascular risk factors. Based on the high prevalence of significant intracranial
      stenosis in the US elderly population, it is feasible and important to perform a
      large-scale population-based study for this disease entity.

PMID- 21860253
TI  - Spinal cord stimulation and cerebral hemodynamics: updated mechanism and
      therapeutic implications.
AB  - The effects of spinal cord stimulation (SCS) on cerebral blood flow (CBF) are
      well known based on experimental investigations, and its vasodilator effect on
      peripheral arteries is widely used in clinical settings in the treatment of
      peripheral vascular disease. Since Hosobuchi's [Appl Neurophysiol 1985;48:372
      376] first observations on the effects of SCS on CBF were published 22 years ago,
      many advances have been made in understanding SCS-mediated effects on CBF. This
      paper reviews the main laboratory observations and analyzes the most significant
      neurophysiological theories on the SCS-mediated effect on CBF. Most significant
      experimental data have been discussed, with specific reference to possible
      mechanisms such as 'functional reversible sympathectomy', cerebral infarction and
      related ischemic edema, hemodynamic deterioration in experimental combined
      ischemic-traumatic brain injury and cerebral vasospasm. The authors revised the
      published experiences in humans with hypoperfusion syndromes and 'adjuvant'
      locoregional CBF increase in chemotherapy of brain tumors. SCS represents a new
      perspective in challenging neurosurgical clinical fields such as cerebral
      ischemia and vasospasm, and seems promising as a new trend of functional
      neurosurgery in cerebrovascular diseases.

PMID- 21860254
TI  - Application of dermal microdialysis for the determination of bioavailability of
      clobetasol propionate applied to the skin of human subjects.
AB  - Dermal microdialysis was used to assess the bioavailability of a topical
      corticosteroid, clobetasol propionate, following application onto the skin of
      human subjects. The penetration of clobetasol propionate from a 4% m/v ethanolic
      solution applied onto 4 sites on one forearm of healthy human volunteers was
      studied. A lipid emulsion, Intralipid(r), was used as the perfusate and linear
      microdialysis probes with a 2-kDa cutoff were inserted intradermally at the
      designated sites. The results indicated that Intralipid could be used as a
      suitable perfusate for in vivo microdialysis of this lipophilic drug of interest.
      Furthermore, the study clearly demonstrated the application of dermal
      microdialysis as a valuable tool to assess the bioavailability/bioequivalence of
      clobetasol propionate penetration into the skin following topical application.

PMID- 21860255
TI  - Co-circulation of G1, G2 and G9 rotaviruses in hospitalized patients in
      Bangladesh during 2006-2009.
AB  - Rotavirus strain diversity in Bangladesh has been explored since 1985 and as seen
      in other parts of the world, rotaviruses have shown tremendous strain diversity
      overtime. Rotavirus antigen was detected in stool specimens using a solid-phase
      sandwich-type enzyme immunoassay. A multiplex reverse transcription polymerase
      chain reaction (RT-PCR) was performed for rotavirus G and P genotypes. This
      current study was carried out between 2006 and 2009 during which time 1,607 (23%)
      of 7,058 fecal specimens tested positive for group A rotaviruses with the highest
      incidence rate being observed in winter each year. Genotyping of rotaviruses
      showed a sharp decline in G2P[4] between 2008 and 2009 with a gradual increase in
      G1 and G9 strains. Since the Government of Bangladesh is planning to include
      rotavirus vaccine in the national immunization program, these data on rotavirus
      strain diversity should be taken into consideration for vaccine strain selection.

PMID- 21860256
TI  - Antibody persistence ten years after first and second doses of 23-valent
      pneumococcal polysaccharide vaccine, and immunogenicity and safety of second and
      third doses in older adults.
AB  - In a study of older adults, first and second doses of 23-valent pneumococcal
      polysaccharide vaccine (PN23) induced IgG increases for all 8 vaccine serotypes
      tested. Participants (N=143, mean age 76 years) were re-enrolled to study
      antibody levels after ten years, and safety and immunogenicity of another PN23
      dose. Ten years after first or second doses, mean IgG concentrations exceeded
      vaccine-naive levels for 7 of 8 serotypes tested. Second and third doses
      administered at this time were generally well tolerated and were immunogenic,
      inducing similar postvaccination levels. Immunogenicity is preserved after
      multiple PN23 doses without evidence of a lower than expected immune response
      (i.e., without hyporesponsiveness).

PMID- 21860257
TI  - Enterovirus infections in young infants: are children still protected by maternal
      antibodies?
AB  - Enterovirus infections are frequent in childhood and may be involved in
      development of several chronic diseases including type 1 diabetes. Maternal
      antibodies have a protective effect in young infants. It has been proposed that
      this protection is now vanishing due to decreasing circulation of enteroviruses
      in Western countries. We aimed to analyse the occurrence of enterovirus
      infections in 55 infants and to assess the protection provided by maternal
      antibodies to these children and the development of enterovirus antibodies in a
      prospective cohort study. In addition, the presence of enteroviruses was detected
      in faeces using RT-PCR and their serotype identified using VP1 region sequencing.
      Our results showed that before polio vaccination 12 of 194 faecal samples were
      positive for enterovirus RNA (coxsackieviruses A4, A5, A16 or echoviruses 13 and
      16). After vaccination Sabin 1, 2 and 3 poliovirus strains predominated in stool
      samples. From birth to 6 months of age polio IgG and IgA increased in most of
      children whereas the levels of other enterovirus antibodies started to increase
      from 6 months to 24 months age. The frequency of maternal neutralizing antibodies
      was generally quite high but still 3 out of 8 infants had no maternal antibodies
      against the enterovirus serotype which they had in stool sample. This study shows
      that enterovirus infections are relatively frequent already before the age of 3
      months. Considerable proportion of infants lack maternal antibodies against the
      virus causing their infection. The significance of this phenomenon needs to be
      evaluated in larger studies.

PMID- 21860258
TI  - Rubella seroprevalence among healthy individuals in Izmir, Turkey.
AB  - In order to assess immunity to rubella in Izmir, Turkey, a total of 600 persons
      of 1-70 years of age were selected with cluster sampling. Of the 597 subjects,
      120(20.1%) was susceptible to the rubella according to their serum antibody
      levels. Of children 1 to 6 years of age, 50.9% was found to be serologically
      susceptible to rubella. Rubella protection rates showed a age-related increase,
      reaching maximum in the 15-19 age group, in which 98.1% of these subjects had
      antibody titre above the full protective level. Of the 126 females in the
      reproductive age group, only 4(3.1%) were found to be serologically susceptible
      to rubella. Logistic regression analysis showed that among the several
      independent variables, only age (p< 0.001) was significantly associated with
      rubella protective antibody levels. Epidemiological studies should continue as
      the epidemiological characteristics of the disease may change depending on the
      uptake of MMR vaccination.

PMID- 21860260
TI  - Improving the delivery of flu vaccine for the older people in times of economic
      recession: what social epidemiology tells us, and what else we need to know.

PMID- 21860261
TI  - A decade of war, wounds, wisdom, and gallantry.

PMID- 21860262
TI  - How does a skilled nursing facility get reimbursed by Medicare? Interview by
      Kathleen D. Schaum.
AB  - Skilled nursing facility wound care nurses should do their part to thoroughly and
      accurately complete the MDS for each patient. They should remember to manage the
      wounds aggressively from day 1. They should also remember to consider the total
      cost of care rather than the cost of a dressing, drug, or piece of equipment.
      These wound care nurses should coordinate care with wound care physicians and
      HOPDs when patients require their services. Finally, SNF wound care nurses should
      take time to read and learn the surgical dressing and negative-pressure LCDs to
      ensure that they obtain the proper orders and that they follow the utilization
      and documentation guidelines required for Medicare Part B coverage of these
      products.

PMID- 21860259
TI  - Anti-angiogenesis immunotherapy.

PMID- 21860263
TI  - Outcome and assessment information set data that predict pressure ulcer
      development in older adult home health patients.
AB  - OBJECTIVES: To identify risk factors for pressure ulcer (PrU) development in
      older adult home health patients from admission Outcome and Assessment
      Information Set (OASIS) data. DESIGN: Retrospective cohort study. SETTING: A
      convenience sample of 5 home healthcare agencies from across the United States.
      PARTICIPANTS: The cohort sample included 5395 nonhospice patients 60 years or
      older who were admitted for intermittent skilled home healthcare between
      September 30, 2007, and January 30, 2009. MAIN MEASURES: OASIS data on age, sex,
      race/ethnicity, diagnoses, caregiving, mental health status, clinical status, and
      functional status relevant to PrU risk were extracted from the electronic medical
      record of eligible patients in participating agencies. Patient OASIS data were
      followed forward chronologically from admission to new PrU development or
      discharge. MAIN RESULTS: The 3323 females (61.6%) and 2072 males (38.4%) ranged
      from age 60 to 103 years (mean, 78.2 [SD, 8.6] years). The cumulative incidence
      of PrUs was 1.3% (n = 71 patients). Multiple logistic regression analyses
      revealed that bowel incontinence, needing assistance with grooming, dependence in
      ability to dress the upper body, dependence in ability to dress the lower body,
      dependence in toileting, inability to transfer, being chairfast or bedfast, and
      the presence of a PrU on admission were positively associated with new PrU
      development. Among patients who were PrU-free on admission, bowel incontinence
      and inability to transfer best predicted PrU development. CONCLUSION: Results
      suggest that OASIS data can be used to identify patients who are at risk for PrUs
      with potential for use nationwide.

PMID- 21860264
TI  - Special considerations in wound bed preparation 2011: an update(c).
AB  - This article builds and expands upon the concept of wound bed preparation
      introduced by Sibbald et al in 2000 as a holistic approach to wound diagnosis and
      treatment of the cause and patient-centered concerns such as pain management,
      optimizing the components of local wound care: Debridement, Infection and
      persistent Inflammation, along with Moisture balance before Edge effect for
      healable but stalled chronic wounds.

PMID- 21860266
TI  - Your meaningful use and international classification of diseases, 10th revision
      checklists.

PMID- 21860267
TI  - Automated reporting of estimated glomerular filtration rate alters referral
      patterns to a nephrology clinic.
AB  - An estimated 11% to 25% of adults in the United States have chronic kidney
      disease (CKD). In 2002, the National Kidney Foundation published a 5-stage
      classification of CKD based on estimated glomerular filtration rate (eGFR)
      intending to improve identification and management of prevalent cases (National
      Kidney Foundation, Am J Kidney Dis. 2002;39:S1-266). Nephrologists anticipated
      that the reporting of estimated GFR would improve early detection of CKD. The
      authors hypothesized that automatic eGFR reporting in our institution would
      subsequently result in increased new nephrology outpatient referrals at an
      earlier stage of CKD. The authors found that the proportion of referrals
      identifying earlier stages of CKD (eGFR greater than 45 mL/min) increased
      significantly for 2 years following the institution of eGFR reporting but was not
      sustained (P = 0.018); this trend was most obvious in African American women. No
      significant trend was seen with respect to age. The authors discuss potential
      reasons for automated eGFR reporting not leading to a sustained increase in
      nephrology referrals.

PMID- 21860268
TI  - The global burden of cancer treatment: reflecting clinical reality in cancer
      nursing research.

PMID- 21860269
TI  - Medication errors reported in a pediatric intensive care unit for oncologic
      patients.
AB  - BACKGROUND: Considering all sources of errors that may occur during healthcare,
      medication errors are the most common and also the most frequent cause of adverse
      events. OBJECTIVE: The objective of the study was to describe the medication
      errors reported in a pediatric intensive care unit for oncologic patients.
      METHODS: This is a descriptive and exploratory study. The errors were reported by
      the professionals involved in the medication system in a medication error report
      form developed for the study. RESULTS: The sample consisted of 110 medication
      errors reported on 71 forms. The omission error was the most common error type
      reported (22.7%), followed by administration error (18.2%). No harm to patients
      was reported in 83.1% of the notifications. CONCLUSION: The analysis of the110
      medication errors provides evidence of the context of their occurrence and the
      need to implement measures that can prevent or intercept these errors.
      IMPLICATIONS FOR PRACTICE: In an institution without adverse events report and a
      formal system to patient safety analysis, the implementation of a local
      nonpunitive approach to medication errors notification represented an important
      tool to patient safety promotion.

PMID- 21860271
TI  - The value of small beginnings.

PMID- 21860272
TI  - Legal risks posed by the electronic medical record. Letter from the editor.

PMID- 21860274
TI  - Conflicting voices: Withhold treatment or not for a patient with chronic self
      destructive behavior?
AB  - Patients with a history of chronic self-destructive and self-injurious behavior
      present many difficulties to healthcare providers. These patients often have
      related substance abuse and personality disorders that complicate their medical
      care. Treatment encounters initially may be related to medical treatment of
      episodic substance intoxicated states with or without self-inflicted injuries.
      Patients later can develop comorbid medical illnesses associated with
      nonadherence of treatment or iatrogenic conditions, both of which result in
      complex end-of-life-care decisions. Institutional familiarity of repeat patients
      often leaves healthcare providers feeling responsible for the patient despite
      having little influence over the patients' ultimate behavioral outcomes. This
      article describes a patient with chronic alcohol abuse, treatment noncompliance,
      severe personality disorder, recurrent suicidal ideation, self-injurious
      behavior, alcoholic cirrhosis, and suicide attempt resulting in multisystem
      injuries leading to an ethical conflict regarding end-of-life care.

PMID- 21860275
TI  - Use of digital health records raises ethics concerns.
AB  - There has been a proliferation in the use of digital health records. Although
      electronic records have many benefits, concerns have been raised about associated
      risks and barriers. This article focuses on risks associated with development,
      utilization, and maintenance of provider-owned electronic medical records and
      institution-owned electronic health records. Strategies to reduce risks and
      overcome barriers are also offered. Attention to these issues can minimize risks
      and improve healthcare services delivered to consumers.

PMID- 21860277
TI  - Practice bulletin guidelines.

PMID- 21860278
TI  - Collaborative practice between obstetricians and midwives.

PMID- 21860279
TI  - 17alpha-hydroxyprogesterone caproate for the prevention of adverse neonatal
      outcome in multiple pregnancies: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether administration of 17alpha-hydroxyprogesterone
      caproate can prevent neonatal morbidity in multiple pregnancies by reducing the
      preterm birth rate. METHODS: We conducted a multicenter, double-blind, placebo
      controlled randomized trial in 55 obstetric clinics in the Netherlands. Women
      with a multiple pregnancy were randomized to weekly injections of either 250 mg
      17alpha-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks
      of gestation and continuing until 36 weeks of gestation. The main outcome measure
      was adverse neonatal outcome. Secondary outcome measures were gestational age at
      delivery and delivery before 28, 32, and 37 weeks of gestation. RESULTS: We
      randomized 671 women. A composite measure of adverse neonatal outcome was present
      in 110 children (16%) born to mothers in the 17alpha-hydroxyprogesterone caproate
      group, and in 80 children (12%) of mothers in the placebo group (relative risk
      [RR] 1.34; 95% confidence interval [CI] 0.95-1.89). The mean gestational age at
      delivery was 35.4 weeks for the 17alpha-hydroxyprogesterone caproate group and
      35.7 weeks for the placebo group (P=.32). Treatment with 17alpha
      hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6%
      in the 17alpha-hydroxyprogesterone caproate group compared with 5% in the placebo
      group, RR 1.04; 95% CI 0.56-1.94), 32 weeks (14% compared with 10%, RR 1.37; 95%
      CI 0.91-2.05), or 37 weeks of gestation (55% compared with 50%, RR 1.11; 95% CI
      0.97-1.28). CONCLUSION: 17alpha-hydroxyprogesterone caproate does not prevent
      neonatal morbidity or preterm birth in multiple pregnancies. CLINICAL TRIAL
      REGISTRATION: ISRCTN Register, www.isrctn.org, ISRCTN40512715.

PMID- 21860280
TI  - Breast carcinoma in young women.
AB  - OBJECTIVE: To estimate the incidence of breast carcinoma and survival in patients
      younger than 25 years old, and to describe presenting clinical signs and symptoms
      of breast cancer in this age group. METHODS: A population-based descriptive study
      and case review in Olmsted County, Minnesota, was conducted using the resources
      of the Rochester Epidemiology Project. Participants were Olmsted County girls and
      women younger than 25 years old with histopathologically confirmed breast
      carcinoma diagnosed between 1935 and 2005. Nonresidents who presented to a
      medical facility within Olmsted County during this time period were included in
      some portions of the analysis. Main outcome measures were age-adjusted incidence,
      5-year survival, and clinical presentation of breast carcinoma in girls and women
      younger than 25 years of age. RESULTS: With four breast carcinomas observed in
      Olmsted County residents over 1,201,539 person-years, the annual age-adjusted
      incidence of breast cancer in this population was 3.2 per million (95% confidence
      interval, 0.1-6.2). All four cancers occurred in the 20- to 24-year age group
      (age-specific incidence, 16.2 per million). Eight additional cases of breast
      carcinoma were identified in nonresidents. Delay in diagnosis was common. All had
      at least one feature worrisome for an aggressive neoplasm identified in their
      clinical history, on physical examination or by imaging. CONCLUSION: Breast
      carcinoma in young women is very rare, associated with delayed diagnosis, and
      usually associated with concerning features requiring biopsy. LEVEL OF EVIDENCE:
      III.

PMID- 21860281
TI  - Thirty-day mortality after primary cytoreductive surgery for advanced ovarian
      cancer in the elderly.
AB  - OBJECTIVE: To identify factors associated with increased 30-day mortality after
      advanced ovarian cancer debulking among elderly women. METHODS: A database
      linking Medicare records with the Surveillance, Epidemiology, and End Results
      (SEER) data was used to identify a cohort of 5,475 women aged 65 and older who
      had primary debulking surgery for stage III or IV epithelial ovarian cancer
      (diagnosed 1995-2005). Women were stratified by acuity of hospital admission.
      Multivariable analysis was performed to identify patient-related and treatment
      related variables associated with 30-day mortality. RESULTS: Five thousand four
      hundred seventy-five women had surgery for advanced ovarian cancer, and the
      overall 30-day mortality was 8.2%. Women admitted electively had a 30-day
      mortality of 5.6% (251 of 4,517), and those admitted emergently had a 30-day
      mortality of 20.1% (168 of 835). Advancing age, increasing stage, and increasing
      comorbidity score were all associated with an increase in 30-day mortality (all
      P<.05) among elective admissions. A group of women at high risk admitted
      electively included those aged 75 or older with stage IV disease and women aged
      75 or older with stage III disease and a comorbidity score of 1 or more. This
      group had an observed 30-day mortality of 12.7% (95% confidence interval 10.7%
      14.9%). CONCLUSION: Age, cancer stage, and comorbidity scores may be helpful to
      stratify electively admitted patients based on predicted postoperative mortality.
      If validated in a prospective cohort, then these factors may help identify women
      who may benefit from alternative treatment strategies. LEVEL OF EVIDENCE: II.

PMID- 21860282
TI  - Cervicovaginal cytology in the detection of recurrence after cervical cancer
      treatment.
AB  - OBJECTIVE: To evaluate the utility of liquid-based cytology in detecting
      recurrent cervical cancer among treated cervical cancer patients. METHODS: A
      retrospective multi-institution study identified patients treated for cervical
      cancer from January 1, 2000, to November 1, 2009, through local cancer registries
      and patient databases. Patients were excluded if they lacked follow-up or
      treatment data. RESULTS: In all, 4,167 cytology results from 929 women were
      identified. Of these, 626 (15%) Pap test results from 312 (34%) women were
      abnormal, including 296 atypical squamous cells of undetermined significance (ASC
      US; 47%); 179 low-grade squamous intraepithelial lesions (LSIL; 29%), 59 atypical
      squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC
      H; 9%); 55 high-grade squamous intraepithelial lesions (HSIL; 9%); 14 atypical
      glandular cells (2%), and 23 favor neoplasia (4%). Abnormal Pap test results led
      to 201 colposcopies in 135 women. Only 45 women had cervical intraepithelial
      neoplasia (CIN) 2 or worse, 25 had CIN 3, and 12 had cancer. Only 5 of 475 (1%)
      women with ASC-US or LSIL had CIN 3. Cancer recurred in 147 women, with 12 (8.1%)
      detected by Pap test; all but one had Pap test results of ASC-H or worse. One
      patient with ASC-US and human papillomavirus had a visible lesion on return for
      assessment 2 months after Pap testing. Colposcopy for cytology less than HSIL
      without a visible lesion on examination did not detect any recurrence or CIN 3.
      When stratified by stage and institution, patients treated with radiation had a
      higher risk of abnormal Pap test results (P<.001). CONCLUSION: A third of
      cervical cancer survivors will have abnormal cytology during follow-up, but in
      the absence of a visible lesion, those with ASC-US or LSIL can be followed
      without colposcopy unless abnormalities persist. Women with ASC-H, HSIL, and
      similar abnormalities deserve colposcopy. LEVEL OF EVIDENCE: II.

PMID- 21860283
TI  - Loop electrosurgical excision procedure: safety and tolerability among human
      immunodeficiency virus-positive Kenyan women.
AB  - OBJECTIVES: To estimate the safety, tolerability, and acceptability of loop
      electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia
      (CIN 2 or 3) in human immunodeficiency virus (HIV)-positive women performed by
      nonphysician health care providers in an HIV care and treatment clinic. METHODS:
      We performed a prospective cohort study among women undergoing LEEP for biopsy
      confirmed CIN 2 or 3 at the Family Acquired Immunodeficiency Syndrome Care and
      Education Services Clinic in Kisumu, Kenya. Women were followed-up 4 weeks after
      the procedure and questioned for abstinence as well as presence and severity of
      side effects after the procedure. The results were analyzed using descriptive
      statistics and univariable and multivariable analysis. RESULTS: Among the 180
      (91%) women who returned for a 4-week follow up after LEEP, 52% reported at least
      one postprocedure symptom, including bleeding, discharge, or pain. Using a Likert
      scale for severity of symptoms, 179 (99%) reported very mild to mild symptoms,
      whereas one (1%) participant described the symptoms as moderate. No participants
      reported severe symptoms. Mean CD4 count was significantly higher among women who
      reported any symptoms compared with women who reported no symptoms after LEEP
      (419 cells/mm compared with 349 cells/mm, P<.05), an association that remained
      significant after adjustment for antiretroviral treatment. The presence or
      severity of postprocedure symptoms did not differ among women who reported sexual
      activity (16%) less than 4 weeks after the procedure. CONCLUSION: LEEP performed
      by clinical officers was well-accepted by HIV-positive women and appears safe,
      resulting in minimal side effects, even among women with early resumption of
      intercourse. LEVEL OF EVIDENCE: II.

PMID- 21860284
TI  - Maternal obesity and risk of postpartum hemorrhage.
AB  - OBJECTIVE: To estimate whether maternal obesity was associated with an increased
      risk for postpartum hemorrhage more than 1,000 mL and whether there was an
      association between maternal obesity and causes of postpartum hemorrhage and mode
      of delivery. METHODS: A population-based cohort study including 1,114,071 women
      with singleton pregnancies who gave birth in Sweden from January 1, 1997 through
      December 31, 2008, who were divided into six body mass index (BMI) classes. Obese
      women (class I-III) were compared with normal-weight women concerning the risk
      for postpartum hemorrhage after suitable adjustments. The use of heparin-like
      drugs over the BMI strata was analyzed in a subgroup. RESULTS: There was an
      increased prevalence of postpartum hemorrhage over the study period associated
      primarily with changes in maternal characteristics. The risk of atonic uterine
      hemorrhage increased rapidly with increasing BMI. There was a twofold increased
      risk in obesity class III (1.8%). No association was found between postpartum
      hemorrhage with retained placenta and maternal obesity. There was an increased
      risk for postpartum hemorrhage for women with a BMI of 40 or higher (5.2%) after
      normal delivery (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.04-1.45])
      compared with normal-weight women (4.4%) and even more pronounced (13.6%) after
      instrumental delivery (OR 1.69, 95% CI 1.22-2.34) compared with normal-weight
      women (8.8%). Maternal obesity was a risk factor for the use of heparin-like
      drugs (OR 2.86, 95% CI 2.22-3.68). CONCLUSION: The increased risk for atonic
      postpartum hemorrhage in the obese group has important clinical implications,
      such as considering administration of prophylactic postpartum uterotonic drugs to
      this group. LEVEL OF EVIDENCE: II.

PMID- 21860285
TI  - Effect of second-trimester and third-trimester rate of gestational weight gain on
      maternal and neonatal outcomes.
AB  - OBJECTIVE: To estimate the effect of second- and third-trimester rate of
      gestational weight gain on pregnancy outcomes using the revised Institute of
      Medicine guidelines. METHODS: This is a retrospective cohort study of singleton
      live births in upstate New York between January 2004 and December 2008. Women
      were grouped by prepregnancy body mass index (BMI) and rates of second- and third
      trimester gestational weight gain were calculated. Women were then classified as
      having less than, within, or greater than recommended rates of gain. Maternal and
      neonatal outcomes were assessed based on rate of weight gain within each BMI
      class. RESULTS: Of 73,977 women meeting inclusion criteria, 4% were underweight,
      48% normal weight, 24% overweight, and 24% obese: 13% class I, 6% class II, and
      5% class III, respectively. After controlling for potential confounding
      variables, less than recommended rates of second- and third-trimester weight gain
      were associated with increased odds of small-for-gestational-age neonates in all
      BMI groups except obese classes II and III. Greater than recommended rates of
      weight gain were associated with increased odds of large-for-gestational-age
      neonates in all BMI groups and increased odds of cesarean delivery in all BMI
      groups with the exception of underweight and obese class III women. CONCLUSION:
      Suboptimal second- and third-trimester rates of gestational weight gain in the
      most obese women, even with net weight loss, do not increase the odds of small
      for-gestational-age neonates. Excessive rates of gestational weight gain increase
      the odds of large-for-gestational-age neonates regardless of BMI. LEVEL OF
      EVIDENCE: II.

PMID- 21860286
TI  - Epidemiologic associations with cerebral palsy.
AB  - OBJECTIVE: To estimate epidemiologic risk factors for cerebral palsy. METHODS:
      Data were collected by linkage to state-based perinatal repositories and cerebral
      palsy registers and using a maternal questionnaire. The cohort included 587
      individuals with cerebral palsy and 1,154 non-cerebral palsy controls. RESULTS:
      The following factors were associated with cerebral palsy: recorded maternal
      infection during pregnancy (41.4% patients compared with 31.3% controls; odds
      ratio [OR] 1.55, 95% confidence interval 1.26-1.91), small for gestational age
      ([birth weight less than third customized centile] 43.9% patients compared with
      6.3% controls; OR 11.75, 6.25-22.08), gestational age less than 32 weeks (29.3%
      patients compared with 0.7% controls; OR 59.20, 28.87-121.38), multiple birth (OR
      6.62, 4.00-10.95), a relative with cerebral palsy (OR 1.61, 1.12-2.32), breech
      position (13.7% patients compared with 6.0% controls; OR 2.48, 1.76-3.49),
      bleeding at any time in pregnancy (29.3% patients compared with 16.9% controls;
      OR 2.04, 1.61-2.58), male sex (58.8% patients compared with 45.8% controls; OR
      1.68, 1.38-2.06), multiple miscarriage (7.7% patients compared with 3.5%
      controls; OR 2.30, 1.38-3.82), smoking (14.0% patients compared with 10.6%
      controls; OR 1.37, 1.02-1.85), and illicit drug use (3.3% patients compared with
      1.5% controls; OR 2.22, 1.14-4.30). Factors not associated with cerebral palsy
      were "disappearing twin," diabetes, maternal body mass index, hypertension,
      alcohol consumption, anemia, maternal hypothyroidism, forceps or vacuum delivery,
      and maternal age. CONCLUSION: Preterm birth, intrauterine growth restriction,
      perinatal infection, and multiple birth present the largest risks for a cerebral
      palsy outcome. Reassuringly, upper respiratory tract and gastrointestinal
      infections during pregnancy were not associated with cerebral palsy. LEVEL OF
      EVIDENCE: II.

PMID- 21860287
TI  - Epidemiology of peripartum cardiomyopathy: incidence, predictors, and outcomes.
AB  - OBJECTIVES: To estimate the incidence, describe the mortality, and identify
      independent predictors of peripartum cardiomyopathy, a very serious
      cardiovascular complication of pregnancy associated with maternal morbidity and
      mortality among otherwise healthy women without prior heart disease. METHODS: We
      identified all cases of diagnosed heart failure that occurred among women within
      1 month before to 5 months after delivery of a liveborn neonate in Kaiser
      Permanente Northern California delivery hospitals between 1995 and 2004. Incident
      peripartum cardiomyopathy was confirmed from medical records documenting dilated
      cardiomyopathy with reduced left ventricular systolic function after excluding
      women with prior heart failure or valvular disease. Data sources included medical
      records, electronic clinical databases, and state birth and death files. RESULTS:
      Among 227,224 eligible women, we confirmed 110 recognized peripartum
      cardiomyopathy cases (incidence: 4.84 per 10,000 live births, 95% confidence
      interval 3.98-5.83). Independent predictors included maternal age of 25 years or
      older, non-Hispanic African American and Filipino groups, parity of 4 or greater,
      multiple gestation, severe anemia, pre-existing and pregnancy-related
      hypertensive disorders, and hemolysis, elevated liver enzymes, low platelets
      syndrome. Maternal death rate (per 1,000 person-years) was higher among cases
      (6.12) than noncases (0.23; P<.001). Neonates whose mothers developed peripartum
      cardiomyopathy experienced poorer clinical outcomes. CONCLUSION: Within a large,
      diverse northern California population, 1 of every 2,066 women delivering a
      liveborn neonate had recognized, confirmed peripartum cardiomyopathy, which was
      associated with higher maternal and neonatal death rates and worse neonatal
      outcomes. Several readily available patient characteristics can be used to
      identify women at risk for this severe pregnancy complication. LEVEL OF EVIDENCE:
      II.

PMID- 21860289
TI  - Mifepristone and misoprostol compared with misoprostol alone for second-trimester
      abortion: a randomized controlled trial.
AB  - OBJECTIVE: To estimate the clinical benefit of pretreatment with mifepristone
      followed by misoprostol compared with misoprostol alone for second-trimester
      abortion. METHODS: Two hundred sixty women with live fetuses of gestational ages
      14-21 weeks were enrolled in a randomized, placebo-controlled, double-blind trial
      in Vietnam. Eligible consenting women received either mifepristone or placebo to
      take on their own at home and were scheduled to return to the hospital the next
      day. At the hospital, women were given 400 micrograms buccal misoprostol every 3
      hours, up to five doses, until both the fetus and placenta were expelled.
      Efficacy was evaluated 15 hours after misoprostol dosing began and the procedure
      was considered complete if uterine evacuation was achieved without recourse to
      surgical evacuation. RESULTS: Pretreatment with mifepristone resulted in more
      than twice the chance of complete uterine evacuation in 15 hours (79.8% compared
      with 36.9%, relative risk 2.16, 95% confidence interval 1.70-2.75). The mean
      induction-to-abortion interval for complete uterine evacuations was statistically
      significantly shorter among participants pretreated with mifepristone compared
      with those given misoprostol alone (8.1, standard deviation 2.8, range 2.5-14.8;
      and 10.6, standard deviation 2.5, range 6.5-15.5 hours, respectively; P<.001).
      The side-effect profiles for the two regimens did not differ significantly and
      acceptability of the treatments was high. CONCLUSION: Mifepristone-misoprostol is
      more efficacious and faster than misoprostol alone. Services offering home
      administration of mifepristone as pretreatment could optimize efficacy and
      acceptability of medical abortions for women with gestations 14-21 weeks since
      the last menstrual period. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT00784186. LEVEL OF EVIDENCE: I.

PMID- 21860288
TI  - Influenza-like illness in hospitalized pregnant and postpartum women during the
      2009-2010 H1N1 pandemic.
AB  - OBJECTIVE: To estimate characteristics and outcomes of pregnant and immediately
      postpartum women hospitalized with influenza-like illness during the 2009-2010
      influenza pandemic and the factors associated with more severe illness. METHODS:
      An observational cohort in 28 hospitals of pregnant and postpartum (within 2
      weeks of delivery) women hospitalized with influenza-like illness. Influenza-like
      illness was defined as clinical suspicion of influenza and either meeting the
      Centers for Disease Control and Prevention definition of influenza-like illness
      (fever 100.0 degrees F or higher, cough, sore throat) or a positive influenza
      test. RESULTS: Of 356 women meeting eligibility criteria, 35 (9.8%) were admitted
      to the intensive care unit (ICU) and four (1.1%) died. Two hundred eighteen women
      (61.2%) were in the third trimester and 10 (2.8%) were postpartum. More than half
      (55.3%) were admitted in October and 25.0% in November with rapidly decreasing
      numbers thereafter. Antiviral therapy was administered to 10.1% of the women
      before hospitalization and to 88.5% during hospitalization. Factors associated
      with an increased likelihood of ICU admission included cigarette smoking (29.4%
      compared with 13.4%; odds ratio [OR] 2.77, 95% confidence interval [CI] 1.19
      6.45) and chronic hypertension (17.1% compared with 3.1%; OR 6.86, 95% CI 2.19
      21.51). Antiviral treatment within 2 days of symptom onset decreased the
      likelihood of ICU admission (31.4% compared with 56.6%, OR 0.36, 95% CI 0.16
      0.77). CONCLUSION: Comorbidities, including chronic hypertension and smoking in
      pregnancy, increase the likelihood of ICU admission in influenza-like illness
      hospitalizations, whereas early antiviral treatment may reduce its frequency.
      LEVEL OF EVIDENCE: II.

PMID- 21860290
TI  - Abortion provision among practicing obstetrician-gynecologists.
AB  - OBJECTIVE: To estimate prevalence and correlates of abortion provision among
      practicing obstetrician-gynecologists (ob-gyns) in the United States. METHODS: We
      conducted a national probability sample mail survey of 1,800 practicing ob-gyns.
      Key variables included whether respondents ever encountered patients seeking
      abortions in their practice and whether they provided abortion services.
      Correlates of providing abortion included physician demographic characteristics,
      religious affiliation, religiosity, and the religious affiliation of the facility
      in which a physician primarily practices. RESULTS: Among practicing ob-gyns, 97%
      encountered patients seeking abortions, whereas 14% performed them. Female
      physicians were more likely to provide abortions than were male (18.6% compared
      with 10.6%, adjusted odds ratio 2.54, 95% confidence interval 1.57-4.08), as were
      those in the youngest age group, those in the Northeast or West, those in highly
      urban postal codes, and those who identify as being Jewish. Catholics,
      Evangelical Protestants, non-Evangelical Protestants, and physicians with high
      religious motivation were less likely to provide abortions. CONCLUSION: The
      proportion of U.S. ob-gyns who provide abortions may be lower than estimated in
      previous research. Access to abortion remains limited by the willingness of
      physicians to provide abortion services, particularly in rural communities and in
      the South and Midwest. LEVEL OF EVIDENCE: II.

PMID- 21860291
TI  - The effect of pack supply on oral contraceptive pill continuation: a randomized
      controlled trial.
AB  - OBJECTIVE: The often small number of oral contraceptive pill (OCP) cycles
      provided may contribute to high rates of discontinuation. We examined the effect
      of an increased OCP supply on 6-month continuation rates. METHODS: This was a
      randomized trial of women initiating OCP use at an urban family-planning clinic
      (n=700). All participants were randomized to receive three or seven cycles of
      OCPs. Participants younger than age 18 years or uninsured received their entire
      supply as packs; those older than age 18 years with insurance were additionally
      randomized to receive either packs or a prescription for refills. We contacted
      participants by telephone 6 months after enrollment to assess OCP continuation
      and adverse events. RESULTS: We obtained follow-up information from 76% of
      participants (260 of 342 in the three-pack group, 244 of 319 in the seven-pack
      group). Participants who received seven packs had higher 6-month continuation
      than participants who received three packs (51% compared with 35%, P<.001). The
      treatment effect was greater among participants younger than 18 years of age (49%
      compared with 12%, P<.001) than among those aged 18 years and older (52% compared
      with 40%, P=.018). Participants who received a prescription were less likely to
      continue OCP use than those who received packs (42% compared with 21%, P=.027).
      Adverse events in the study were rare and not associated with receiving more OCP
      packs. CONCLUSION: A greater OCP supply at the time of initiation can improve
      continuation rates, especially among women younger than 18 years of age. CLINICAL
      TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00677742.
      LEVEL OF EVIDENCE: I.

PMID- 21860292
TI  - Timing of copper intrauterine device insertion after medical abortion: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare intrauterine device (IUD) use at 6 months in women
      randomized to receive an intrauterine copper contraceptive 1 week compared with 1
      month after medical abortion. METHODS: We recruited women undergoing medical
      abortion with mifepristone and misoprostol and choosing the copper IUD for
      contraception. We randomly assigned participants to "immediate" insertion 1 week
      after mifepristone or "delayed" insertion 4-6 weeks later. We followed rates of
      IUD insertion, 6-month utilization, expulsion, removal, and pregnancy.
      Participants recorded bleeding in a diary for 4 weeks. RESULTS: We randomized 156
      participants. We inserted an IUD in 97% of participants in the immediate group
      and 76% in the delayed group (P<.001). At 6 months, 69% of participants in the
      immediate group used the IUD compared with 60% in the delayed group (P=.24).
      Expulsion rates were comparable; 12% (8 of 69) in the immediate group compared
      with 11% (7 of 65) in the delayed group. Removals occurred in 14% (10 of 69) of
      immediate and 8% (5 of 65) of delayed group participants (P=.21). Four
      pregnancies occurred in delayed group participants who did not return for IUD
      insertion (P=.09). The immediate and delayed groups reported a median of 20 and
      19 bleeding or spotting days, respectively (P=.15). We detected no cases of
      serious infection, uterine perforation, or hemorrhage. CONCLUSION: Immediate
      insertion increased uptake of the IUD without increasing expulsions or bleeding.
      CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinialtrials.gov, . LEVEL
      OF EVIDENCE: I.

PMID- 21860293
TI  - Risk factors for exposure, pain, and dyspareunia after tension-free vaginal mesh
      procedure.
AB  - OBJECTIVE: To identify possible risk factors for exposure, dyspareunia, and pain
      after insertion of tension-free vaginal mesh in pelvic organ prolapse surgery.
      METHODS: This was a prospective observational cohort study. Consecutive women who
      underwent surgery with a trocar-guided tension-free vaginal mesh kit were
      included and evaluated at 6 weeks and at 6 and 12 months after surgery with
      respect to anatomy and complications. Logistic regression analysis was performed
      to identify risk factors for exposure, dyspareunia, and pain. RESULTS: Two
      hundred ninety-four patients were included. Exposure was found in 34 patients
      (12%). Smoking and total mesh were risk factors for exposure (odds ratio [OR]
      3.1, 95% confidence interval [CI] 1.1-8.7 and OR 3.0, 95% CI 1.2-7.0,
      respectively). Clinical and surgical experience were inversely related to the
      risk of exposure (OR 0.5, 95% CI 0.3-0.8 per decade). Pain (OR 3.2, 95% CI 1.2
      8.4) and dyspareunia (OR 4.7, 95% CI 1.7-12.8) before surgery were predictive for
      pain and dyspareunia after surgery, respectively. Pain after surgery was found in
      35 out of 275 (13%) patients and dyspareunia was found in 77 out of 171 (45%)
      patients. LEVEL OF EVIDENCE: Smoking, total tension-free vaginal mesh, and
      experience were predictive factors for mesh exposure.

PMID- 21860294
TI  - Diagnostic accuracy of retrograde and spontaneous voiding trials for
      postoperative voiding dysfunction: a randomized controlled trial.
AB  - OBJECTIVE: To compare the diagnostic accuracy of two voiding trial methods to
      predict postoperative voiding dysfunction. METHODS: Women undergoing operations
      for urinary incontinence, prolapse, or both urinary incontinence and prolapse
      from November 2009 and March 2010 were randomized into one of two groups:
      retrograde or spontaneous. All patients underwent both techniques of voiding
      trials with randomization determining order. RESULTS: Fifty women were randomized
      to 25 per group. Failure rates were 62% for retrograde and 84% for spontaneous.
      Women who failed both had 12.6+/-14.4 days of retention compared with 2.5+/-2.1
      days for those who failed only one method (P=.004). The retrograde method had
      94.4% sensitivity and 58.1% specificity to detect postoperative voiding
      dysfunction lasting at least 7 days compared with the spontaneous method with
      100% sensitivity and 25.8% specificity. Positive and negative predictive values
      for the retrograde method were 56.7% and 94.7%, respectively, compared with the
      spontaneous method with 43.9% and 100%. Retrograde was preferred by patients
      (51.1% compared with 44.4%) regardless of randomization. CONCLUSION: The
      retrograde method is more accurate in evaluating postoperative voiding
      dysfunction, although both tests had a low positive predictive value. A longer
      period of retention was seen with failure of both methods. Retrograde was
      preferred by patients and provides an efficient alternative to the spontaneous
      method of voiding trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT01091844. LEVEL OF EVIDENCE: I.

PMID- 21860295
TI  - Smoking and bladder symptoms in women.
AB  - OBJECTIVE: To estimate the relation of smoking status and smoking intensity with
      bladder symptoms. METHODS: Questionnaires were mailed to 3,000 women (aged 18-79
      years) randomly identified from the Finnish Population Register. Case definitions
      for stress urinary incontinence (SUI), urgency, and urgency urinary incontinence
      (UUI) were "often" or "always" based on reported occurrence (never, rarely,
      often, always). Case definitions for urinary frequency were based on reporting of
      longest voiding interval as less than 2 hours and for nocturia reporting of at
      least two voids per night. Potential confounders included comorbidities,
      medications, sociodemographic, lifestyle, and reproductive factors. RESULTS:
      Responses totaled 2,002 (67.0%). Frequency was reported by 7.1%, nocturia 12.6%,
      SUI 11.2%, urgency 9.7%, and UUI 3.1%. In the multivariable analyses, smoking was
      associated with urgency (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.7
      4.2 for current and OR 1.8, CI 1.2-2.9 for former compared with never smokers)
      and frequency (OR 3.0, CI 1.8-5.0 for current and OR 1.7, CI 1.0-3.1 for former
      smokers) but not with nocturia and SUI. Adjusted prevalence differences between
      never and current smokers were 6.0% (3.0-9.1%) for urgency and 6.0% (3.3-8.7%)
      for frequency. Similarly, current heavy (compared with light) smoking was
      associated with additional risk of urgency (OR 2.1, CI 1.1-3.9) and frequency (OR
      2.2, CI 1.2-4.3). CONCLUSION: Urgency and frequency are approximately three times
      more common among current than never smokers. Parallel associations for urgency
      and frequency with smoking intensity suggest a dose-response relationship.
      Nocturia and SUI are not associated with smoking. These results suggest an
      additional rationale for smoking cessation in women seeking medical attention for
      bladder symptoms and highlight the diversity between such symptoms. LEVEL OF
      EVIDENCE: II.

PMID- 21860296
TI  - Simulation training in an obstetric clerkship: a randomized controlled trial.
AB  - OBJECTIVE: To estimate the effect of simulation training on the confidence of
      medical students to perform a vaginal delivery. METHODS: Medical students on 12
      consecutive rotations were recruited and randomly assigned to a traditional
      lecture on performing a vaginal delivery or a lecture plus hands-on vaginal
      delivery simulation. Participants completed confidence assessment questionnaires
      at baseline and 4 weeks after training. End-of-rotation examination scores were
      also compared. RESULTS: One-hundred thirteen students participated (94.9% of
      those eligible). Students receiving simulation training were significantly more
      confident in their ability to perform a vaginal delivery immediately after
      assessment than students who did not receive the simulation training (P<.01);
      however, these differences narrowed over time. Compared with lecture-only
      students, simulation students scored significantly higher on their oral (P=.004)
      and written examinations (P=.009) 4 weeks after the intervention. CONCLUSION: A
      single obstetric simulation is more effective than lecture only for increasing
      students' end-of-rotation oral and written examination scores. LEVEL OF EVIDENCE:
      I.

PMID- 21860297
TI  - Cost-effectiveness of maternal treatment to prevent perinatal hepatitis B virus
      transmission.
AB  - OBJECTIVE: To estimate the cost-effectiveness of maternal lamivudine or hepatitis
      B immune globulin (HBIG) treatment, in addition to standard neonatal
      immunoprophylaxis, for the prevention of perinatal hepatitis B virus
      transmission. METHODS: A decision-tree model was created to estimate the cost
      effectiveness of maternal administration of either lamivudine or HBIG in the
      third trimester to prevent perinatal hepatitis B transmission compared with no
      maternal treatment. The model was first estimated for each treatment using
      overall transmission rates, and then stratified by maternal hepatitis B virus DNA
      viral load. RESULTS: The model estimated that for each 100 hepatitis B surface
      antigen positive pregnant women treated with lamivudine, 9.7 cases of chronic
      hepatitis B virus infections are prevented, with a cost-savings of $5,184 and 1.3
      life-years gained per patient treated. For HBIG, 9.5 cases of chronic hepatitis B
      virus infections are prevented for each 100 pregnant women treated, with a cost
      savings of $5,887 and 1.2 life-years gained per patient treated. Under baseline
      assumptions, lamivudine remains cost-saving unless the reduction in perinatal
      transmission is less than 18.5%, and HBIG remains cost-saving unless the
      reduction in perinatal transmission is less than 9.6%. CONCLUSION: In this
      decision analysis, administration of lamivudine or HBIG to hepatitis B surface
      antigen positive pregnant women for the prevention of perinatal transmission of
      hepatitis B is cost-savings across a wide range of assumptions. LEVEL OF
      EVIDENCE: III.

PMID- 21860298
TI  - Obstetrician and nurse-midwife collaboration: successful public health and
      private practice partnership.
AB  - OBJECTIVE: To evaluate maternal and neonatal outcomes of collaborative maternity
      care for a socioeconomically diverse patient population in a California community
      hospital. METHODS: Collaborative practice structure and clinical guidelines were
      analyzed, as were de-identified electronic medical records for all primiparous
      women who delivered term singletons between 2000 and 2010 (N=4,426).
      Demographics, care processes, and perinatal outcomes were compared among women
      seen prenatally in a private collaborative practice compared with a Federally
      Qualified Health Center prenatal clinic run by nurse-midwives. RESULTS: Evidence
      based practices were used to achieve excellent perinatal outcomes. Three quarters
      of women received intrapartum nurse-midwifery care (74.4%). Few differences were
      seen in management or outcomes among women from different prenatal clinics
      despite significant variation in demographic and clinical characteristics.
      Private practice patients were older, less likely to be obese, and more likely to
      speak English compared with counterparts from public health clinics. They were
      also more likely to use hydrotherapy or epidural analgesia, or experience severe
      perineal laceration and repair. Overall, pharmacologic pain relief methods were
      limited: less than a quarter of primiparous women used narcotics (21.2%),
      epidural analgesia (23.7%), or warm water immersion (23.2%). Labor induction and
      augmentation, and cesarean delivery rates (12.5%), were similar among groups and
      low overall. CONCLUSION: A collaborative practice of low-tech, high-touch care
      results in high-quality maternity services. The care model holds promise for
      replication to address health disparities by limiting obstetric interventions and
      warrants further investigation with regard to associated costs and resultant
      outcomes. LEVEL OF EVIDENCE: III.

PMID- 21860299
TI  - A northwest collaborative practice model.
AB  - Collaborative practice between obstetrician-gynecologists and certified nurse
      midwives has been successful at the Family Beginnings obstetric unit at Group
      Health for at least three reasons. Each provider group is able to practice
      independently and thus give the kind of maternity and women's health care sought
      by the local community. The legal framework in Washington State supports a wide
      range of maternity care practices and includes a reasonable provider insurance
      scheme. The boundaries between different groups operating within distinct scopes
      of practice are well-defined and communicated. This allows providers to smoothly
      share or transfer clients from midwife to obstetrician and back as needed in each
      case. The success of the Family Beginnings model is demonstrated by a favorable
      comparison with national and Washington State metrics of delivery outcomes.
      Replicating the model elsewhere depends on building support for collaborative
      maternity care across the obstetric and midwifery professions in states where an
      appropriate legal framework exists, and in institutions where policies for
      credentialing nurse midwives are in place. Where these supports do not exist, all
      practitioners jointly advocating for more enlightened approaches is recommended.

PMID- 21860300
TI  - Great minds don't think alike: collaborative maternity care at San Francisco
      General Hospital.
AB  - For more than 30 years the collaboration between obstetrician-gynecologists and
      certified nurse-midwives at San Francisco General Hospital has led to the
      provision of high-quality care to women and families. This enduring partnership
      has been sustained by shared goals and values, most notably a commitment to
      excellence in both providing care to the underserved and training the next
      generation of physicians and nurse-midwives. Success has also depended on a
      mutual respect for differences that has enabled the collaborative to capitalize
      on the distinct expertise of each partner. The balance struck between
      independence and interdependence of the practice groups has led to innovation and
      successes that might otherwise not have come to being, while also enabling the
      collaborative to overcome the inevitable conflicts and challenges that arise
      within this type of long-standing partnership. This model holds promise for
      replication in other settings and informs broader considerations of health policy
      and regulation.

PMID- 21860301
TI  - Making it work: successful collaborative practice.
AB  - There are three major examples of collaborative programs between certified nurse
      midwives (CNMs) and obstetrician-gynecologists at Baystate Medical Center in
      Springfield, Massachusetts, within the Department of Obstetrics and Gynecology.
      One program is a midwifery practice that serves a diverse population in a
      hospital-based office, four neighborhood health centers, and a correctional
      facility. Another program provides a triage function for patients who present to
      the hospital with obstetric or gynecologic problems. The third program introduces
      a team approach to the education of residents with a CNM having primary
      responsibility for teaching normal obstetrics to first-year residents and medical
      students in collaboration with attending physicians. Keys to success include an
      understanding of the principles of collaborative practice, the use of a detailed
      practice agreement between midwives and attending physicians, keeping open lines
      of communication, understanding and accepting differing philosophies of practice,
      and, most importantly, maintaining trust across all levels of providers.

PMID- 21860302
TI  - The rising cesarean delivery rate in America: what are the consequences?
AB  - Cesarean delivery is now the most common operation in the United States, and it
      has increased dramatically from 5.8% in 1970 to 32.3% in 2008. This rise has not
      resulted in significant improvement in neonatal morbidity or maternal health.
      Three recent studies of elective repeat cesarean deliveries performed before 39
      completed weeks of gestation have demonstrated increased respiratory and other
      adverse neonatal outcomes. Maternal mortality in the United States has increased
      from 10 per 100,000 to 14 per 100,000 from 1998 to 2004. Contributing to this in
      an increasing incidence of placenta accreta associated with multiple uterine
      scars requiring the need for emergency cesarean hysterectomy, blood transfusion,
      and maternal mortality due to obstetric hemorrhage. To reverse the trend of the
      rising cesarean delivery rate, obstetricians must reduce the primary rate and
      avoid the performance of a uterine incision unless absolutely necessary for fetal
      or maternal indications. For women with one previous low transverse cesarean
      delivery, obstetricians should promote a trial of labor after previous cesarean
      delivery in those women who desire three or more children.

PMID- 21860303
TI  - Clinical management of endometriosis.
AB  - Endometriosis is a relatively common chronic gynecologic disorder that usually
      presents with chronic pelvic pain or infertility. The societal effect of this
      disorder is enormous both in monetary costs and in quality of life. The diagnosis
      of the disease can only be definitively made with surgical intervention.
      Fertility may be enhanced with surgical intervention, but medical suppressive
      therapy has no role apart from in vitro fertilization. Assisted reproductive
      technology is associated with excellent outcomes. Management of endometriomas is
      particularly complex because surgical intervention may reduce ovarian reserve.
      Both medical and surgical treatment of endometriosis-associated chronic pelvic
      pain are effective in the short-term. Recurrence is common with both modalities.
      Recurrence after surgical intervention can be decreased with the use of
      postoperative suppressive medical therapy such as hormonal contraceptives. This
      article presents the different types of peritoneal disease found in endometriosis
      patients. The technique used to safely and completely remove the disease is
      discussed. The specific areas of involvement include the pelvic side wall, the
      cul-de-sac, and bladder peritoneum.

PMID- 21860304
TI  - Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.
AB  - BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to
      prevent a luteinizing hormone (LH) surge during controlled ovarian
      hyperstimulation (COH) without the hypo-estrogenic side-effects, flare-up, or
      long down-regulation period associated with agonists. The antagonists directly
      and rapidly inhibit gonadotrophin release within several hours through
      competitive binding to pituitary GnRH receptors. This property allows their use
      at any time during the follicular phase. Several different regimes have been
      described including multiple-dose fixed (0.25 mg daily from day six to seven of
      stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14
      to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of
      stimulation) protocols, with or without the addition of an oral contraceptive
      pill. Further, women receiving antagonists have been shown to have a lower
      incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable
      clinical outcomes for the antagonist and agonist protocols, these benefits would
      justify a change from the standard long agonist protocol to antagonist regimens.
      This is an update of a Cochrane review first published in 2001, and previously
      updated in 2006. OBJECTIVES: To evaluate the effectiveness and safety of
      gonadotrophin-releasing hormone (GnRH) antagonists compared with the standard
      long protocol of GnRH agonists for controlled ovarian hyperstimulation in
      assisted conception cycle. SEARCH STRATEGY: We performed electronic searches of
      major databases, for example Cochrane Menstrual Disorders and Subfertility Group
      Specialized Register, CENTRAL, MEDLINE, EMBASE (from 1987 to April 2010); and
      handsearched bibliographies of relevant publications and reviews, and abstracts
      of major scientific meetings, for example the European Society of Human
      Reproduction and Embryology (ESHRE) and American Society for Reproductive
      Medicine (ASRM). SELECTION CRITERIA: : Two review authors independently screened
      the relevant citations for randomized controlled trials (RCTs) comparing
      different agonist versus antagonist protocols in women undergoing IVF or ICSI.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      risk of bias and extracted data. If relevant data were missing or unclear, the
      authors were contacted for clarification. MAIN RESULTS: Forty-five RCTs (n=7511)
      comparing the antagonist to the long agonist protocols fulfilled the inclusion
      criteria. There was no evidence of a statistically significant difference in
      rates of live-births (9 RCTs; odds ratio (OR) 0.86, 95% CI 0.69 to 1.08). There
      was a statistically significant lower incidence of OHSS in the GnRH antagonist
      group (29 RCTs; OR 0.43, 95% CI 0.33 to 0.57). AUTHORS' CONCLUSIONS: The use of
      antagonist compared with long GnRH agonist protocols was associated with a large
      reduction in OHSS and there was no evidence of a difference in live-birth rates.

PMID- 21860306
TI  - Diagnosis, pathophysiology, and management of mood disorders in pregnant and
      postpartum women.

PMID- 21860308
TI  - Society for women's health oversight: establishing equality in the profession of
      obstetrics and gynecology.

PMID- 21860310
TI  - Surgical removal of a gigantic abdominal mass: a multidisciplinary approach.

PMID- 21860313
TI  - Practice bulletin no. 123: thromboembolism in pregnancy.
AB  - Pregnant women have a fourfold to fivefold increased risk of thromboembolism
      compared with nonpregnant women (1, 2). Approximately 80% of thromboembolic
      events in pregnancy are venous (3), with a prevalence of 0.5-2.0 per 1,000
      pregnant women (4-9). Venous thromboembolism, including pulmonary embolism,
      accounts for 1.1 deaths per 100,000 deliveries (3), or 9 % of all maternal deaths
      in the United States (10). In the developing world, the leading cause of maternal
      death is hemorrhage (11); however, in developed nations, where hemorrhage is more
      often successfully treated and prevented, thromboembolic disease is one of the
      leading causes of death (12). The prevalence and severity of this condition
      during pregnancy and the peripartum period warrant special consideration of
      management and therapy. Such therapy includes the treatment of acute thrombotic
      events and prophylaxis for those at increased risk of thrombotic events. The
      purpose of this document is to provide information regarding the risk factors,
      diagnosis, management, and prevention of thromboembolism, particularly venous
      thromboembolism in pregnancy.

PMID- 21860314
TI  - Practice bulletin no. 124: inherited thrombophilias in pregnancy.
AB  - Inherited thrombophilias are associated with an increased risk of venous
      thromboembolism and also have been linked to adverse outcomes in pregnancy.
      However, there is limited evidence to guide screening for and management of these
      conditions in pregnancy. The purpose of this document is to review common
      thrombophilias and their association with maternal venous thromboembolism risk
      and adverse pregnancy outcomes, indications for screening to detect these
      conditions, and management options in pregnancy.

PMID- 21860315
TI  - Committee opinion no. 502: primary ovarian insufficiency in the adolescent.
AB  - Primary ovarian insufficiency has been diagnosed in adolescents as young as age
      14 years. It is estimated that approximately 1% of the female population in the
      United States is affected by primary ovarian insufficiency. Evaluation for all
      potential causes of amenorrhea, or a change from regular to irregular menses for
      3 or more consecutive months, including pregnancy, polycystic ovary syndrome,
      hypogonadal amenorrhea, thyroid abnormalities, hyperprolactinemia, or primary
      ovarian insufficiency is important for young females. Understanding the unique
      concerns and needs associated with the diagnosis and treatment of ovarian
      insufficiency in adolescents is essential for the provision of quality health
      care for this population.

PMID- 21860316
TI  - Committee opinion number 503: tobacco use and women's health.
AB  - Tobacco use negatively affects every organ system and is the most prevalent cause
      of premature death for adults within the United States. Compared with women who
      are nonsmokers, women who smoke cigarettes have greater risks of reproductive
      health problems, many forms of gynecologic cancer and other types of cancer,
      coronary and vascular disease, chronic obstructive lung disease, and
      osteoporosis. Brief behavioral counseling and the use of evidence-based smoking
      cessation aids are effective strategies for achieving smoking cessation even for
      very heavy smokers. The trained obstetrician-gynecologist is well positioned to
      screen and counsel all patients on tobacco use and to advocate for smoke-free
      environments. Smoking cessation counseling is often reimbursed by health
      insurers. Tobacco use has deleterious effects on women through all stages of
      life.Tools are available for obstetrician-gynecologists to screen for and treat
      tobacco abuse and give the appropriate coding for smoking cessation counseling.

PMID- 21860317
TI  - Committee opinion no. 504: Screening and diagnosis of gestational diabetes
      mellitus.
AB  - Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance that
      begins or is first recognized during pregnancy, is associated with increased
      maternal, fetal, and neonatal risks. The prevalence of GDM in the United States
      is increasing, probably because of increasing rates of overweight and obesity. A
      universal recommendation for the ideal approach for screening and diagnosis of
      GDM remains elusive. At this time, the Committee on Obstetric Practice continues
      to recommend a two-step approach to screening and diagnosis. All pregnant women
      should be screened for GDM, whether by patient history, clinical risk factors, or
      a 50-g, 1-hour glucose challenge test at 24-28 weeks of gestation. The diagnosis
      of GDM can be made based on the result of the 100-g, 3-hour oral glucose
      tolerance test, for which there is evidence that treatment improves outcome.

PMID- 21860318
TI  - Committee opinion no. 505: understanding and using the U.S. Medical Eligibility
      Criteria For Contraceptive Use, 2010.
AB  - The 2010 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC)
      issued by the Centers for Disease Control and Prevention gives comprehensive,
      evidence-based guidance to clinicians providing family planning services to
      women, especially women with medical conditions. The American College of
      Obstetricians and Gynecologists endorses the U.S. MEC and encourages its use by
      Fellows.

PMID- 21860319
TI  - Committee opinion no. 506: expedited partner therapy in the management of
      gonorrhea and chlamydia by obstetrician-gynecologists.
AB  - Expedited partner therapy is the clinical practice of treating the sex partners
      of patients, in whom sexually transmitted infections are diagnosed, by providing
      prescriptions or medications to the patient to take to his or her partner(s)
      without the health care provider first examining the partner(s). The American
      College of Obstetricians and Gynecologists supports expedited partner therapy in
      the management of gonorrhea and chlamydial infections when the partner is
      unlikely or unable to otherwise receive in-person evaluation and appropriate
      treatment. The legality of expedited partner therapy is ambiguous in some states
      and overt legal impediments exist in others; analysis suggests that the practice
      is permissible in 27 states. Clinicians practicing in states where expedited
      partner therapy is legal should use it for eligible patients. In states,
      territories, and other jurisdictions where expedited partner therapy is not legal
      or the legal status of expedited partner therapy is unclear or ambiguous,
      clinicians are encouraged to advocate for its legality and implementation and
      work with their health departments to develop protocols for the use of expedited
      partner therapy. All health care providers should advocate for greater
      availability of sexually transmitted infection services.

PMID- 21860320
TI  - Committee opinion no. 507: human trafficking.
AB  - Human trafficking is a widespread problem with estimates ranging from 14,000 to
      50,000 individuals trafficked into the United States annually. This hidden
      population involves the commercial sex industry, agriculture, factories, hotel
      and restaurant businesses, domestic workers, marriage brokers, and some adoption
      firms. Because 80% of trafficked individuals are women and girls, women's health
      care providers may better serve their diverse patient population by increasing
      their awareness of this problem. The exploitation of people of any race, gender,
      sexual orientation, or ethnicity is unacceptable at any time, in any place. The
      members of the American College of Obstetricians and Gynecologists should be
      aware of this problem and strive to recognize and assist their patients who are
      victims or who have been victims of human trafficking.

PMID- 21860321
TI  - Subarachnoid hemorrhage during sexual activity after sildenafil intake: an
      accidental association?
AB  - We report and describe an autopsy case of a man dead for rupture of cerebral
      artery aneurysm with subsequent subarachnoid hemorrhage after sexual intercourse.
      Toxicologic analysis demonstrated that he had consumed sildenafil (Viagra).
      Although subarachnoid hemorrhage has been reported to be associated with sexual
      intercourse, it is not among the known adverse effects of sildenafil. However,
      sildenafil has been found to interact with vascular physiology via multiple
      mechanisms and in most of the vascular districts of the human body. This case
      provides an example of a very rare association between this drug and a fatal
      pathologic event and deserves to be added to the existing clinical knowledge
      about sildenafil and the pathophysiology of the events involved. This knowledge
      may be helpful in orienting further investigation into the mechanisms of action
      of sildenafil and their clinical implications.

PMID- 21860322
TI  - Deaths related to chemical burns.
AB  - The authors present a series of 6 deaths due to the uncommon cause of chemical
      burns. Of the 6 deaths due to chemical burns, 4 deaths were due to ingestion of a
      chemical, 1 death was caused by chemical burns of the skin, and 1 death resulted
      from rectal insufflation of a chemical. Seven additional cases where chemical
      burns may have been a contributing factor to the death or an incidental finding
      are also presented. Four cases are related to an incident involving chemical
      exposure during an industrial explosion. Three cases involve motor fuel burns of
      the skin. Two cases concern a plane crash incident, and 1 case involved a
      vehicular collision. Cases are derived from the records of the Dallas County
      Medical Examiner's Office and those of the authors' consultation practices. Each
      of the cases is presented, followed by a discussion of the various mechanisms of
      chemical injury.

PMID- 21860323
TI  - One-in-a-million shot: a homicidal thoracic air rifle wound, a case report, and a
      review of the literature.
AB  - A homicidal shooting with an air gun is reported. The history, mechanisms of
      action, and crime scene implications of air guns are discussed. The wounds
      produced by air guns are compared to those produced by powder firearms.

PMID- 21860324
TI  - Nonpharmacological management of apathy in dementia:  a systematic review.
AB  - Apathy is one of the most challenging and prevalent behavioral symptoms of
      dementia. It is associated with increased disability and caregiver frustration as
      well as reduced quality of life, rehabilitation outcomes and survival after
      nursing home admission. A literature search to set criteria yielded 56
      nonpharmacological intervention studies with outcomes relevant to apathy in
      dementia. Studies were rated according to quality and categorized into 7 groups:
      exercise, music, multisensory, animals, special care programming, therapeutic
      activities and miscellaneous. Despite a lack of methodological rigor, it is
      apparent that nonpharmacological interventions have the potential to reduce
      apathy. This review indicates that therapeutic activities, particularly those
      provided individually, have the best available evidence for effectiveness in
      dementia. Recommendations are provided for quality research.

PMID- 21860325
TI  - Lung pathologic findings in a local residential and working community exposed to
      World Trade Center dust, gas, and fumes.
AB  - OBJECTIVE: To describe pathologic findings in symptomatic World Trade Center
      exposed local workers, residents, and cleanup workers enrolled in a treatment
      program. METHODS: Twelve patients underwent surgical lung biopsy for suspected
      interstitial lung disease (group 1, n = 6) or abnormal pulmonary function tests
      (group 2, n = 6). High-resolution computed axial tomography and pathologic
      findings were coded. Scanning electron microscopy with energy-dispersive x-ray
      spectroscopy was performed. RESULTS: High-resolution computed axial tomography
      showed reticular findings (group 1) or normal or airway-related findings (group
      2). Pulmonary function tests were predominantly restrictive. Interstitial
      fibrosis, emphysematous change, and small airway abnormalities were seen. All
      cases had opaque and birefringent particles within macrophages, and examined
      particles contained silica, aluminum silicates, titanium dioxide, talc, and
      metals. CONCLUSIONS: In symptomatic World Trade Center-exposed individuals,
      pathologic findings suggest a common exposure resulting in alveolar loss and a
      diverse response to injury.

PMID- 21860326
TI  - Sarcoidosis diagnosed after September 11, 2001, among adults exposed to the World
      Trade Center disaster.
AB  - OBJECTIVE: Explore relationships between World Trade Center (WTC) exposures and
      sarcoidosis. METHODS: Sarcoidosis has been reported after exposure to the WTC
      disaster. We ascertained biopsy-proven post-9/11 sarcoidosis among WTC Health
      Registry enrollees. Cases diagnosed after Registry enrollment were included in a
      nested case-control study. Controls were matched to cases on age, sex, race or
      ethnicity, and eligibility group (eg, rescue or recovery worker). RESULTS: We
      identified 43 cases of post-9/11 sarcoidosis. Twenty-eight incident cases and 109
      controls were included in the case-control analysis. Working on the WTC debris
      pile was associated with sarcoidosis (odds ratio 9.1, 95% confidence interval 1.1
      to 74.0), but WTC dust cloud exposure was not (odds ratio 1.0, 95% confidence
      interval 0.4 to 2.8). CONCLUSIONS: Working on the WTC debris pile was associated
      with an elevated risk of post-9/11 sarcoidosis. Occupationally exposed workers
      may be at increased risk.

PMID- 21860327
TI  - Association of general fatigue with cellular immune indicators among healthy
      white-collar employees.
AB  - OBJECTIVE: Although fatigue is a common complaint in the working population,
      underlying immunological mechanisms are not well understood. This study
      investigated the association of general fatigue with cellular immune indicators.
      METHODS: A total of 148 healthy white-collar employees (70% men) underwent a
      blood draw for the measurement of natural killer (NK), B, and T cell counts as
      well as NK cell cytotoxicity (NKCC) and completed two different fatigue scales,
      that is, Profile of Mood State (POMS) and Maastricht Questionnaire (MQ). RESULTS:
      Multiple linear regression analyses revealed that POMS fatigue score was
      significantly associated with decreases of NK cells (beta = -.407) and NKCC (beta
      = -.215), whereas MQ fatigue score was significantly associated with reduced NK
      cells (beta = -.290) but not with NKCC (beta = -.127). CONCLUSION: The results
      suggest that general fatigue may be related to impaired NK cell competency among
      healthy employees.

PMID- 21860328
TI  - Effectiveness of a worksite wellness program on health behaviors and personal
      health.
AB  - OBJECTIVE: To evaluate the effectiveness of a worksite wellness program at
      improving health behavior and personal health. METHODS: Analyses are based on 472
      (71% men and 29% women) workers employed in 2009 through 2010. RESULTS:
      Participants showed significant improvement in frequency of exercise, consumption
      of whole grains, vegetables and fruits, restful sleep, and seat belt use. Life
      satisfaction and perceived health also significantly increased, but job
      satisfaction significantly decreased and there was no change in smoking or body
      mass index. In addition, the percentage with borderline/high blood pressure
      significantly decreased. CONCLUSIONS: Participation in well-structured worksite
      wellness programs, such as the one evaluated in this study, may increase health
      and life satisfaction for employees. This type of wellness program appears to
      help employees develop and maintain healthy behaviors.

PMID- 21860329
TI  - Talking about health: correction employees' assessments of obstacles to healthy
      living.
AB  - OBJECTIVE: Describe health risks/obstacles to health among correctional
      employees. METHODS: Mixed-methods approach combined results from four focus
      groups, 10 interviews, 335 surveys, and 197 physical assessments. RESULTS:
      Obesity levels were higher than national averages (40.7% overweight and 43.3%
      obese), with higher levels associated with job tenure, male gender, and working
      off-shift. Despite widespread concern about the lack of fitness, leisure exercise
      was higher than national norms. Respondents had higher levels of hypertension
      than national norms, with 31% of men and 25.8% of women hypertensive compared
      with 17.1% and 15.1% for national norms. Stress levels were elevated. Officers
      related their stress to concerns about security, administrative requirements, and
      work/family imbalance. High stress levels are reflected in elevated levels of
      hypertension. CONCLUSIONS: Correctional employees are at high risk for chronic
      disease, and environmental changes are needed to reduce risk factors.

PMID- 21860330
TI  - Pressure ulcer prevention program: a journey.
AB  - The Centers for Medicare & Medicaid Services' regulations regarding nonpayment
      for hospital-acquired conditions such as pressure ulcers have prompted a marked
      increase in focus on preventive care. Our hospital also used this change in
      payment policy as an opportunity to strengthen our pressure ulcer prevention
      practices. We used an 8-spoke prevention wheel to develop and implement practice
      changes that reduced pressure ulcer incidence from 7.3% to 1.3% in 3 years.
      Because it is about the journey, we will describe the mechanisms we designed and
      implemented, and identify strategies that worked or did not work as we
      promulgated a quality improvement process for pressure ulcer prevention in our
      large urban hospital center.

PMID- 21860331
TI  - Effect of oxidized regenerated cellulose/collagen matrix on proteases in wound
      exudate of patients with diabetic foot ulcers.
AB  - PURPOSE: The aim of this study was to investigate the influence of oxidized
      regenerated cellulose/collagen matrix on the concentration and activity of
      gelatinases, elastase, and plasmin in wound exudate. SUBJECTS AND SETTING: The
      study included 32 patients with diabetic foot ulcers. Ten patients with a mean
      age of 66 +/- 9 years (mean +/- SD) were treated with hydrocolloid dressings; 22
      patients with a mean age of 57 +/- 12 years were treated with oxidized
      regenerated/collagen matrix and hydrocolloid dressings. METHODS: Wound exudate
      was collected on days 0, 5, 14, and every 14 days thereafter for 12 weeks. Total
      protein was determined according to Bradford's technique. The levels of elastase
      and plasmin were measured spectrofluorometrically. Besides, gelatinase activity
      and matrix metalloproteinase-2 concentration were analyzed. The surface area of
      all ulcers was measured by planimetry. RESULTS: Patients treated with oxidized
      regenerated cellulose/collagen matrix showed a significant decrease in elastase,
      plasmin, and gelatinase activities in wound exudates. The matrix
      metalloproteinase-2 concentration was significantly reduced on days 14, 28, 42,
      and 56 in comparison to day 0. Furthermore, wound size was significantly reduced
      at days 14 and 28 in oxidized regenerated cellulose/collagen matrix-treated
      patients (P < .05). CONCLUSION: Our results showed a significant and immediate
      reduction in the levels of all tested proteases in the wound exudate of diabetic
      foot ulcer patients treated with oxidized regenerated cellulose/collagen matrix.
      These patients also experienced a significantly greater reduction in wound size.

PMID- 21860332
TI  - pH in the bacteria-contaminated wound and its impact on clostridium histolyticum
      collagenase activity: implications for the use of collagenase wound debridement
      agents.
AB  - PURPOSE: We sought to understand the influence of pH on Clostridium collagenase
      activity, using both in vitro and in vivo, and to understand the influence of
      bacterial contamination on pH in vivo. DESIGN: Artificial wound eschar was used
      for the assessment of debridement efficacy in vitro and the wound fluid of a
      contaminated pig wound model was used for examining pH during healing using in
      vivo techniques. METHODS: We used a collagen-based artificial wound eschar to
      test collagenase activity in the collagenase product under various pH conditions.
      We evaluated bacterial contaminated wounds, using a pig wound model with a
      bacterial load including Pseudomonas aeruginosa, coagulase-negative
      staphylococci, and Fusobacterium sp to track the pH of wounds in relation to
      bacterial load. RESULTS: The pH levels in the wound fluid were all above neutral.
      They varied from 9.2 on day 1 to 8.3 on day 10. Collagenase achieved its highest
      activity around a pH of 8.5 when tested in Tris-buffered saline. Using artificial
      wound eschar, the optimal pH range for C collagenase was determined to be more
      than a pH of 6. The total initial microbial load (day 0) was higher than levels
      at any other time during the study. The levels of P aeruginosa began to decrease
      on day 1, but by day 4 the total pseudomonas population had rebounded to near day
      0 levels. This was followed by a distinct decrease and by day 21 levels were
      lower than those on day 0. The coagulase negative staphylococci (CNS) population
      behaved differently than the pseudomonas population, decreasing and remaining
      decreased relative to day 0 through day 14. However, by day 21 the CNS population
      had increased to near day 0 levels. This greatly influenced the increase in total
      bioburden by day 21, indicating that it was primarily due to the increase in CNS.
      CONCLUSION: The data demonstrate that wound pH in a model of contaminated pig
      wounds is alkaline during the first 10 days of healing. As healing progresses, pH
      decreases with no significant change in the level of bacterial bioburden. C
      collagenase exhibited robust activity in the pH range found in this contaminated
      pig wound model, suggesting it can effectively debride necrotic tissue in the
      environment found in most chronic wounds in humans.

PMID- 21860333
TI  - Skin blood flow response to 2-hour repositioning in long-term care residents: a
      pilot study.
AB  - PURPOSE: The purpose of this noninvasive pilot study was to examine the changes
      in transcutaneous oxygen (tcO2), skin temperature, and hyperemic response in the
      heels, sacrum, and trochanters in a 2-hour loading-unloading condition in nursing
      home residents who are positioned in supine and lateral positions. DESIGN: A 1
      group, prospective, repeated-measures design was used. SUBJECTS AND SETTING: Nine
      subjects (5 males, 4 females) with a mean age of 85.3 +/- 10.86 years (mean +/-
      SD) who required help in turning and positioning at a skilled nursing facility
      participated in the study. METHODS: Oxygen and temperature sensors were placed on
      the heels, trochanters, and sacrum. The subject was (1) positioned lateral for 30
      minutes (preload); (2) turned to the supine position with head of the bed at 30
      degrees  for 2 hours (both sacrum and heels were on the bed surface) (loading);
      and (3) positioned lateral for 2 hours (unloading). Subjects were turned to
      either the right or the left side. RESULTS: Friedman test showed no statistical
      differences in tcO2 or skin temperature on the sacrum, heels, or trochanters
      during preload, supine, and lateral positioning (P > .5). Individual data
      revealed that hyperemic response was seen in 6 of the 9 subjects when the
      position was changed from supine to lateral. Only one-third of the subjects
      attained a sacral tcO2 of 40 mm Hg or more at the end of the 2-hour lateral
      positioning. tcO2 on both heels decreased within the first 30 minutes of loading.
      CONCLUSION: Two hours of staying in the supine position lowered sacral
      oxygenation to less than 40 mm Hg, in some subjects, regardless of whether there
      was adequate tcO2 at preload. Repositioning to a lateral position after 2 hours
      of placement in a supine position did not cause the tcO2 to return to preload
      level. The efficacy of a 2-hour repositioning schedule requires further
      investigation. Since heel tcO2 was reduced after 30 minutes of loading, further
      work is needed to determine whether the heels should be offloaded with more
      frequent repositioning.

PMID- 21860334
TI  - Kit for preparation of multimeric receptor-specific 99mTc-radiopharmaceuticals
      based on gold nanoparticles.
AB  - BACKGROUND: Multivalency is a design principle by which organized arrays amplify
      the strength of a binding process, such as the binding of multimeric peptides to
      specific receptors located on cell surfaces. The conjugation of peptides to gold
      nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with
      target-specific molecular recognition. AIM: The aim of this research was to
      develop a kit for technetium-99m (99mTc) labelling of AuNPs that are conjugated
      to Lys3-bombesin, cyclo[Arg-Gly-Asp-D-Phe-Lys-(Cys)] or thiol-mannose to produce
      receptor-specific multimeric systems. METHODS: A freeze-dried kit formulation for
      the instant preparation of 99mTc-ethylenediamine-N,N'-diacetic acid
      (EDDA)/hydrazinonicotinyl (HYNIC)-Tyr3-octreotide (99mTc-EDDA/HYNIC-TOC) (vial 1)
      and a second vial containing 1.5 ml of AuNP solution (1 nM, 20 nm diameter,
      surface area=1260 nm2, 37,000 surface Au atoms, 1.05 * 10 particles) plus 10 ul
      of Lys3-bombesin, cyclo[Arg-Gly-Asp-D-Phe-Lys-(Cys)] or mannose (50 uM,
      approximately 285 molecules per AuNP) (vial 2) were prepared. Multimeric
      radiopharmaceuticals were prepared by adding 1 ml of 0.2 mol/l phosphate buffer,
      pH 7.0, and 1 ml of 99mTcO4- (4 GBq) to vial 1, and the mixture was incubated at
      92 degrees C for 20 min in a dry block heater. A total of 100 ul (200 MBq) of
      99mTc-EDDA/HYNIC-TOC solution (122 HYNIC-TOC molecules per AuNP) was added to
      vial 2. No further purification was carried out. Radiochemical purity was
      determined by instant thin-layer chromatography-silica gel/2-butanone (Rf values
      for the radiolabelled AuNP and 99mTcO4- were 0.0 and 1.0, respectively),
      ultrafiltration, size-exclusion high-pressure liquid chromatography and a PD-10
      column. The conjugates were characterized by ultraviolet-visible, far-infrared
      and X-ray photoelectron spectroscopy. In-vitro binding studies were carried out
      in alphanubeta3 receptor-positive C6 glioma cancer cells, gastrin-releasing
      peptide receptor-positive PC3 cancer cells or mannose receptor-positive rat liver
      cells. Biodistribution studies were carried out in athymic mice with induced
      tumours (PC-3 or C6 cancer cells) or in Wistar rats (99mTc-AuNP-mannose for
      sentinel lymph node detection). Images were obtained using a micro-single-photon
      emission computed tomography/computed tomography system. RESULTS: Radiochemical
      purity was 96 +/- 2% for all of the multimeric radiopharmaceuticals. Far-infrared
      showed a characteristic band at 279 +/- 1 cm-1, which was assigned to the Au-S
      bond. ultraviolet-visible and X-ray photoelectron spectroscopy also indicated
      that the AuNPs were functionalized with peptides or mannose. Radiopharmaceuticals
      showed specific recognition for receptors expressed in cancer cells or rat liver
      cells. Micro-single-photon emission computed tomography/computed tomography
      images showed clear tumour uptake and lymph node accumulation. The kit (i.e. vial
      1 and vial 2) demonstrated excellent stability during storage at 4 degrees C for
      6 months. CONCLUSION: Multimeric systems of 99mTc-AuNP-peptide/mannose prepared
      from kits exhibited properties suitable for use as target-specific agents for
      molecular imaging of tumours and sentinel lymph node detection.

PMID- 21860335
TI  - Use of leukocyte counts in evaluation of early-onset neonatal sepsis.
AB  - BACKGROUND: Early-onset sepsis is a common diagnosis in neonatal intensive care
      units. Because of the low incidence, overtreatment is also common. OBJECTIVE: To
      measure the sensitivity and negative predictive value of 2 serial white blood
      cell counts and a negative blood culture at 24 hours in predicting a noninfected
      neonate in the evaluation of early-onset sepsis. METHODS: We performed a
      historical cohort study of neonates in the University of Massachusetts Newborn
      Nursery and neonatal intensive care unit born between 1999 and 2008 who had
      sepsis evaluations within the first 24 hours of life. RESULTS: Three thousand two
      hundred thirteen patients were identified; 59 were excluded due to missing data.
      Of the 3154 included neonates, 1539 (49%) had 2 normal immature to total
      neutrophil (I:T) ratios and a negative blood culture at 24 hours. Two of these
      blood cultures showed growth of bacteria after 24 hours but were considered
      contaminants, and antibiotics were stopped at 48 hours. None of the 1539 neonates
      with normal I:T ratios was subsequently diagnosed with sepsis (negative
      predictive value 100%; [95% confidence interval: 99.905%-100%]). CONCLUSIONS: In
      this study, the combination of 2 serial normal I:T ratios and a negative blood
      culture at 24 hours in the evaluation of early-onset sepsis shortly after birth
      is indicative of a noninfected neonate. This suggests that antibiotics can safely
      be stopped at 24 hours in these neonates, which comprises approximately 50% of
      our study population.

PMID- 21860336
TI  - Hospital course and short-term outcomes of term and late preterm neonates
      following exposure to prolonged rupture of membranes and/or chorioamnionitis.
AB  - Our objective was to characterize the hospital course and short-term outcomes of
      neonates exposed to prolonged rupture of membranes (PROM), chorioamnionitis (CH),
      or both PROM and CH. Outcomes were positive blood culture and/or clinical signs
      of infection (+BC/CSI) prompting >4 days of antibiotics. Six neonates had a
      positive BC, 2 (0.6%) in the CH group and 4 (2.7%) in the PROM + CH group (P =
      0.05); none of the neonates exposed to PROM alone had a +BC. These results
      support our current approach of withholding routine antibiotic therapy in
      neonates exposed to PROM alone.

PMID- 21860337
TI  - beta-Lactam resistance, serotype distribution, and genotypes of meningitis
      causing Streptococcus pneumoniae, Rio de Janeiro, Brazil.
AB  - BACKGROUND: Here, we report a laboratory-based study of Streptococcus pneumoniae
      recovered from patients with meningitis in Rio de Janeiro State, Brazil. METHODS:
      The aim of this study was to determine the evolution of beta-lactam resistance,
      antimicrobial susceptibility pattern, serotypes, and genetic diversity of S.
      pneumoniae, isolated from meningitis patients between 2000 and 2008. RESULTS: A
      total of 264 S. pneumoniae recovered from patients between 2000 and 2008 were
      included. Susceptibility testing (E-test) of S. pneumoniae showed resistance to
      penicillin, ceftriaxone, oxacillin, cotrimoxazole, tetracycline, ofloxacin,
      erythromycin, chloramphenicol, and rifampicin. Penicillin resistance (PEN-R,
      minimal inhibitory concentration [MIC] >= 0.12 MUg/mL) increased from 8% of
      isolates in 2000-2002, to 12% in 2003-2005, and to 20% in 2006-2008. Ceftriaxone
      resistance (MIC >= 1.0 MUg/mL) was detected among some PEN-R isolates (13%) from
      2004 onward. Within the PEN-R isolates, serotypes that are included in 10-valent
      pneumococcal conjugate vaccine predominated (90%), and resistance was detected
      mostly in isolates of serotypes 14 (61%), 23F (16%), 6B (10%), and 19F (3%).
      Multilocus sequence typing showed that 52% of the PEN-R isolates, and 89% of
      those with MICs >= 0.5 MUg/mL, were sequence type (ST)-156 or single-locus
      variants of this ST (ST-557 or ST-4388); all of these isolates were serotype 14
      and were assigned to the Spain-3 clone. CONCLUSIONS: beta-lactam resistance
      increased recently among cerebrospinal fluid isolates and was mainly due to the
      surge of the ST-4388, a previously undescribed gki single-locus variants of ST
      156. Regional surveillance is shown to be essential to provide optimal
      antimicrobial therapy, monitor highly successful clones, and formulate adequate
      vaccination strategy.

PMID- 21860338
TI  - RNA viruses in young Nepalese children hospitalized with severe pneumonia.
AB  - BACKGROUND: Pneumonia is among the leading causes of illness and death in
      children <5 years of age worldwide. There is little information on the viral
      etiology of severe pneumonia in low-income countries, where the disease burden is
      particularly high. METHODS: We analyzed nasopharyngeal aspirates from 629
      children 2 to 35 months of age meeting World Health Organization criteria for
      severe pneumonia and presenting at Kanti Children's Hospital, Kathmandu, Nepal,
      from January 2006 through June 2008. We examined one specimen from each child for
      7 respiratory viruses using reverse transcription polymerase chain reaction.
      RESULTS: We detected one or more respiratory viruses in 188 (30%; confidence
      interval: 26.4%-33.7%) of the 627 specimens with a valid polymerase chain
      reaction result, of which 88 (14%) yielded respiratory syncytial virus (RSV), 28
      (4.5%) influenza A, 24 (5.8%) parainfluenza virus (PIV) type 3, 23 (3.7%) PIV
      type 1, 17 (2.7%) influenza B, 9 (1.4%) human metapneumovirus, and 5 (0.8%) PIV
      type 2. Episodes of severe pneumonia occurred in an epidemic pattern with 2 main
      annual peaks, the viral infections contributing importantly to these epidemics.
      The largest peaks of severe pneumonia coincided with peaks of RSV infection,
      which occurred during the last part of the monsoon season and in winter.
      CONCLUSIONS: RSV was the dominant respiratory viral pathogen detected in young
      Nepalese children hospitalized with severe pneumonia.

PMID- 21860339
TI  - Integration of absorption, distribution, metabolism, and elimination genotyping
      data into a population pharmacokinetic analysis of nevirapine.
AB  - OBJECTIVES: The aim of this analysis was to show the applicability of a newly
      developed algorithm to assess the influence of genetic variants and other
      covariates on nevirapine's drug disposition. The algorithm combines high
      throughput genotyping data and nonlinear mixed effects modeling methods. METHODS:
      Patients, who participated in the 2NN pharmacokinetic sub study, were reconsented
      and reenrolled into a clinical trial for genotyping analysis. Overall, 198 single
      nucleotide polymorphisms located in 45 absorption, distribution, metabolism, and
      elimination related genes were genotyped using the Illumina BeadArray technology.
      Data analysis was performed using NONMEM VI and SAS 9.1.3. RESULTS: Overall, 1260
      nevirapine plasma concentrations were obtained from 271 genotyped patients.
      Plasma concentration-time profiles of nevirapine were best described by a one
      compartment model with auto-induced first-order elimination process. Nevirapine
      clearance was 19.4% reduced in Asian/Black patients, compared with
      Caucasian/Hispanic patients. For single nucleotide polymorphism rs3745274 (CYP2B6
      516G>T) heterozygous patients (GT) showed a 15.3% reduced clearance; patients
      with homozygous CYP2B6 516TT alleles showed a 30.6% reduced clearance compared to
      patients with homozygous 516GG alleles. Patients carrying the homozygote genotype
      of rs12768009 (CYP2C19 8403AA), highly linked to rs4244285 (CYP2C19*2), showed a
      26.8% reduced clearance compared with patients with CYP2C19 8403 AG and GG
      alleles. CONCLUSION: By integration of high-throughput genotyping data into a
      pharmacometric analysis of nevirapine, the impact of the CYP2B6 516G>T
      polymorphism on nevirapine's exposure was confirmed and quantified. In addition,
      a new hypothesis with regard to CYP2C19 involvement in nevirapine metabolism has
      been generated. The analysis presented might help to optimize and individualize
      the therapy for patients treated with nevirapine to add to their therapeutic
      benefit.

PMID- 21860340
TI  - Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral
      fluid, and sweat during treatment of opioid-dependent pregnant women.
AB  - BACKGROUND: Buprenorphine is currently under investigation as a pharmacotherapy
      to treat pregnant women for opioid dependence. This research evaluates
      buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP
      Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high
      dose (14-20 mg) BUP sublingual tablet administration in three opioid-dependent
      pregnant women. METHODS: Oral fluid and sweat specimens were collected in
      addition to plasma specimens for 24 hours during gestation weeks 28 or 29 and 34,
      and 2 months after delivery. Time to maximum concentration was not affected by
      pregnancy; however, BUP and NBUP maximum concentration and area under the curve
      at 0 to 24 hours tended to be lower during pregnancy compared with postpartum
      levels. RESULTS: Statistically significant but weak positive correlations were
      found for BUP plasma and OF concentrations and BUP/NBUP ratios in plasma and oral
      fluid. Statistically significant negative correlations were observed for times of
      specimen collection and BUP and NBUP oral fluid/plasma ratios. BUP-Gluc and NBUP
      Gluc were detected in only 5% of oral fluid specimens. In sweat, BUP and NBUP
      were detected in only four of 25 (12 or 24 hours) specimens in low concentrations
      (less than 2.4 ng/patch). CONCLUSION: These preliminary data describe BUP and
      metabolite pharmacokinetics in pregnant women and suggest that, like methadone,
      upward dose adjustments may be needed with advancing gestation.

PMID- 21860341
TI  - Oral fluid nicotine markers to assess smoking status and recency of use.
AB  - INTRODUCTION: Oral fluid collection is noninvasive and easily observed making it
      an attractive matrix for objectively determining smoking status. Despite large
      intersubject variability, cotinine oral fluid concentrations correlate with
      cigarettes smoked per day (CPD). Few studies, however, assessed nicotine markers
      in oral fluid other than cotinine; other markers might improve smoking status
      assessment and/or time of last cigarette. MATERIALS AND METHODS: Smoking
      histories and oral fluid specimens were collected from nontreatment-seeking light
      (1-10 CPD) and heavy smokers (greater than 10 CPD) and from environmentally
      exposed and nonexposed nonsmokers who provided written informed consent for this
      Institutional Review Board-approved study. Nicotine, cotinine, hydroxycotinine
      (OH-cotinine), and norcotinine oral fluid concentrations were quantified by
      liquid chromatography tandem mass spectrometry. RESULTS: Comparison of 1, 3, and
      10 ng/mL oral fluid liquid chromatography tandem mass spectrometry cutoffs
      demonstrated that 10-ng/mL cutoffs performed optimally for cotinine, OH-cotinine,
      nicotine, and norcotinine identifying 98%, 97%, 88%, and 15% of self-reported
      smokers; 1% nonsmokers had greater than 10 ng/mL cotinine. No self-reported
      nonsmoker had greater than 10 ng/mL OH-cotinine, nicotine, or norcotinine.
      Norcotinine was only identified in smokers' oral fluid. Oral fluid nicotine,
      cotinine, and nicotine/cotinine ratios were correlated with time of last smoking
      (r = -0.53, -0.23, and -0.51; P < 0.05) and CPD (r = 0.35, 0.26, and 0.33; P <
      0.01), respectively. DISCUSSION AND CONCLUSION: OH-cotinine performed slightly
      better than cotinine for distinguishing smokers from nonsmokers and should be
      considered as an additional oral fluid smoking indicator. Further research is
      required to determine if oral fluid norcotinine is a marker for distinguishing
      light and heavy smokers. Moderate correlations suggest nicotine, cotinine, and
      nicotine/cotinine ratios may be useful for determining smoking recency in "spot
      samples" collected during nicotine cessation treatment.

PMID- 21860342
TI  - MDMA and metabolite disposition in expectorated oral fluid after controlled oral
      MDMA administration.
AB  - INTRODUCTION: The use of 3,4-methylenedioxymethamphetamine (MDMA) is increasing,
      enhancing the need for its detection in clinical, workplace, pain management, and
      driving under the influence of drugs testing programs. Oral fluid is an important
      alternative matrix for drug testing, but little is known about MDMA detection
      windows in oral fluid. AIMS: The aim was to characterize MDMA and metabolite
      disposition in expectorated oral fluid after controlled MDMA administration.
      METHODS: Placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral MDMA doses were
      given double-blind in random order in separate sessions to 29 healthy adults with
      histories of MDMA use. One thousand two hundred eighty-six expectorated oral
      fluid specimens collected up to 7 days after dosing were analyzed for MDMA, 3,4
      methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4
      hydroxy-3-methoxyamphetamine (HMA) by gas chromatography mass spectrometry. The
      limits of quantification were 5 ng/mL for MDMA and MDA and 10 ng/mL for HMA and
      HMMA. RESULTS: MDMA was the primary analyte detected, with concentrations up to
      12,000 ng/mL in 872 specimens (67.8%). MDA was quantified in 656 specimens
      (51.0%) at concentrations <403 ng/mL and was never present without concurrent
      MDMA. HMA and HMMA were not detected. Of the specimens, 59.8%, 58.6%, and 54.9%
      were found to be MDMA positive at the Talloires (20 ng/mL), Driving under the
      Influence of Drugs, Alcohol, and Medicines (25 ng/mL) and proposed US Substance
      Abuse and Mental Health Services Administration (50 ng/mL) confirmation cutoffs,
      respectively. MDMA was first observed in oral fluid 0.25-1.25 hours after dosing;
      MDA was initially detected at 0.5-1.75 hours. In general, the windows of
      detection for MDMA and MDA were 47 and 29 hours, respectively, although a few
      specimens were positive up to 71 and 47 hours. CONCLUSIONS: Oral fluid monitoring
      efficiently detects single, recreational 70-150 mg of MDMA use for 1-2 days.
      These controlled administration data provide a scientific basis for interpreting
      MDMA oral fluid test results.

PMID- 21860343
TI  - Nonsteroidal anti-inflammatory drugs may reduce enterohepatic recirculation of
      mycophenolic acid in patients with childhood-onset systemic lupus erythematosus.
AB  - BACKGROUND: The large interindividual differences observed in mycophenolic acid
      (MPA) pharmacokinetics (MPA-PK) are in part attributed to the large variability
      in enterohepatic recirculation (EHC) of the drug. The main metabolite of MPA, MPA
      glucuronide is actively secreted into the bile via the multidrug resistance
      associated protein 2 (MRP2) transporter. Nonsteroidal anti-inflammatory drugs
      (NSAIDs) have been shown to inhibit the MRP2 transporter, which can alter EHC and
      drug exposure. Here, we evaluated the effects of this potential drug-transporter
      interaction on MPA-PK in a cohort of patients with childhood-onset systemic lupus
      erythematosus on mycophenolate mofetil therapy. MATERIALS AND METHODS: Full MPA
      concentration-time profiles and demographics including comedications were
      available for 19 patients with childhood-onset systemic lupus erythematosus.
      Concentrations at predose (C(trough)), 9 hour (C9), and nadir (C(nadir); defined
      as the lowest concentration between C(max) and C9), and area under the curve
      (AUC0-12 and AUC6-12) were assessed using standard methods (WinNonlin5.1). AUC6
      12/AUC0-12 and C9/C(nadir) ratios were used to evaluate the effects of NSAID
      treatment on MPA-PK. RESULTS: Eleven out of 19 patients were on NSAID treatment
      and did not show visual evidence of EHC in their PK profile. In contrast,
      patients not on NSAID therapy showed evidence of EHC-related MPA concentration
      increase in the later part of their PK profiles, typically after 6 hours. This
      phenomenon could be well characterized by the C9/C(nadir) ratio, which was
      significantly lower in the NSAID-treated cohort (P < 0.01). CONCLUSIONS: These
      preliminary data suggest that the concomitant intake of NSAIDs may lower EHC of
      MPA possibly through the inhibition of MRP2 transport of MPA-G. Further mechanism
      based studies are needed to further elucidate this potential transporter
      interaction.

PMID- 21860344
TI  - Effect of Chinese medicines Chan Su, Asian ginseng, Siberian ginseng, and
      American ginseng on a new digoxin immunoassay based on luminescent oxygen
      channeling technology.
AB  - BACKGROUND: Chan Su, Asian ginseng, Siberian ginseng, and American ginseng are
      known to interfere with various digoxin immunoassays. Recently, a homogeneous
      sequential chemiluminescent assay for digoxin based on the luminescent oxygen
      channeling technology (LOCI digoxin) for application on the Dimension and Vista
      platform has been introduced into the market. The effects of interference by Chan
      Su and various ginsengs on this new immunoassay have not yet been reported.
      MATERIALS AND METHODS: Aliquots of a drug-free serum pool were supplemented with
      Chan Su, Asian ginseng, Siberian ginseng, and American ginseng representing the
      expected in vivo concentrations after normal usage and cases of overdose. Serum
      digoxin concentrations were measured using the LOCI digoxin assay on the Vista
      1500 analyzer. We also prepared 3 digoxin pools from patients receiving digoxin.
      Two digoxin pools were supplemented with these traditional medicines to
      investigate their effect on serum digoxin measurements. Mice were fed Chan Su
      extract to determine the potential of in vivo derived interfering factors. The
      possibility of eliminating interference of Chan Su on serum digoxin measurement
      was also investigated, by measuring free digoxin concentration after
      supplementing aliquots of the third digoxin pool with various amounts of Chan Su
      extract. RESULTS: A clinically significant interference by Chan Su with serum
      digoxin measurement was observed using the LOCI digoxin assay. The various
      ginsengs demonstrated negligible effects. In addition, apparent digoxin
      concentrations were observed in sera of mice after feeding them with Chan Su; the
      half-life of digoxin-like immunoreactive components was approximately 1 hour.
      Moreover, serum digoxin concentrations were significantly elevated in the
      presence of Chan Su, whereas the various ginsengs exhibited no effect. Monitoring
      free digoxin can only partly eliminate the interference of Chan Su in serum
      digoxin measurement. CONCLUSIONS: Chan Su interferes with serum digoxin
      measurement using the LOCI Digoxin, whereas the ginsengs demonstrated no
      measurable interference at clinically relevant concentrations.

PMID- 21860345
TI  - Rising HIV-1 viral load set point at a population level coincides with a fading
      impact of host genetic factors on HIV-1 control.
AB  - OBJECTIVE: Heterozygosity for a 32 base pair deletion in the CCR5 gene
      (CCR5wt/Delta32) and the minor alleles of a single-nucleotide polymorphism in the
      HCP5 gene (rs2395029) and in the HLA-C gene region (-35HLA-C; rs9264942) has been
      associated with a lower viral load set point. Recent studies have shown that over
      calendar time, viral load set point has significantly increased at a population
      level. Here we studied whether this increase coincides with a fading impact of
      above-mentioned host genetic markers on HIV-1 control. METHODS: We compared the
      association between viral load set point and HCP5 rs2395029, -35HLA-C rs9264942,
      and the CCR5wt/Delta32 genotype in HIV-1-infected individuals in the Netherlands
      who had seroconverted between 1982 and 2002 (pre-2003 seroconverters, n = 459) or
      between 2003 and 2009 (post-2003 seroconverters, n = 231). RESULTS: Viral load
      set point in post-2003 seroconverters was significantly higher than in pre-2003
      seroconverters (P = 4.5 * 10(-5)). The minor alleles for HCP5 rs2395029, -35HLA-C
      rs9264942 and CCR5wt/Delta32 had a similar prevalence in both groups and were all
      individually associated with a significantly lower viral load set point in pre
      2003 seroconverters. In post-2003 seroconverters, this association was no longer
      observed for HCP5 rs2395029 and CCR5wt/Delta32. The association between viral
      load set point and HCP5 rs2395029 had significantly changed over time, whereas
      the change in impact of the CCR5wt/Delta32 genotype over calendar time was not
      independent from the other markers under study. CONCLUSION: The increased viral
      load set point at a population level coincides with a lost impact of certain host
      genetic factors on HIV-1 control.

PMID- 21860346
TI  - Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by
      increasing HIV-1 drug resistance mutations in drug-naive patients.
AB  - OBJECTIVES: To evaluate the frequency and progression over time of the WHO
      defined transmitted HIV-1 drug resistance mutations (DRMs) among antiretroviral
      treatment (ART)-naive HIV-1-infected patients in Cameroon. DESIGN: We analyzed
      HIV-1 DRM data generated from 369 ART-naive individuals consecutively recruited
      between 1996 and 2007 in urban and rural areas in Cameroon. METHODS: HIV-1 drug
      resistance genotyping was performed in the pol gene using plasma samples and
      surveillance DRMs were identified using the 2009 WHO-DRM list. RESULTS: We
      observed in Yaounde, the capital city, an increasing prevalence of DRMs over
      time: 0.0% (none of 61 participants) in 1996-1999; 1.9% (one of 53 participants)
      in 2001; 4.1% (two of 49 participants) in 2002; and 12.3% (10 of 81 participants)
      in 2007. In the rural areas with more recently implemented ART programs, we found
      DRMs in six of 125 (4.8%) ART-naive individuals recruited in 2006-2007. DRMs
      identified in both areas included resistance mutations to protease inhibitors,
      nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) that
      might impair the efficacy of available first-line and second-line treatments.
      CONCLUSION: This report showed an increase in transmitted DRMs in areas where
      antiretroviral drugs were introduced earlier, although other factors such as
      natural viral polymorphisms and acquired DRMs through exposure to antiretroviral
      cannot be totally excluded. Further surveillances are needed to confirm this
      evolution and inform public health policies on adequate actions to help limit the
      selection and transmission of drug-resistant HIV, while scaling up access to ART
      in developing countries.

PMID- 21860348
TI  - Al Andalus Ultra Trail: an observation of medical interventions during a 219-km,
      5-day ultramarathon stage race.
AB  - OBJECTIVE: To record the injuries and health problems suffered by ultramarathon
      runners during a 219-km, 5-day stage race and to help race organizers plan
      medical provision for these events. DESIGN: Observational study. SETTING: Al
      Andalus Ultra Trail 2010, in southern Spain. PARTICIPANTS: All 69 ultramarathon
      runners. MAIN OUTCOME MEASURES: Total numbers and percentages of each clinical
      encounter with a health professional and their respective health problems.
      RESULTS: Sixty-nine competitors started the race, and 39 runners were seen with a
      medical problem (56.5%). There were a total of 99 clinical encounters. The most
      common reasons for consulting were foot blisters (33.3%), followed by chafing
      (9.1%). Lower limb musculoskeletal injuries accounted for 22.2%, predominantly
      affecting the knee. CONCLUSIONS: This is the first report of a multistage
      ultramarathon race where medical coverage was present throughout and has reported
      on musculoskeletal, dermatological, and other medical problems. When providing
      medical coverage for stage events, the medical team needs to promote practices
      that minimize injury and address both running-related injuries and non-running
      related injuries, taking account of environmental conditions.

PMID- 21860347
TI  - Impact of treatment with raltegravir during primary or chronic HIV infection on
      RNA decay characteristics and the HIV viral reservoir.
AB  - BACKGROUND: Eradication of HIV-1 is prevented by the formation of viral
      reservoirs in peripheral blood, lymphoid tissues and other sanctuary sites. In
      most patients, rebound upon treatment cessation is prompt. We assessed whether
      early treatment with raltegravir can impact on the formation of the viral
      reservoir. METHODS: We conducted an open-label, nonrandomized study, and assessed
      in detail the decay characteristics of HIV-1 RNA in plasma, HIV DNA in CD4 T
      cells and colon tissue biopies (CTBs) in 16 treatment-naive patients during
      either primary (PHI, n = 8) or chronic (CHI, n = 8) HIV-1 infection after
      treatment with raltegravir and Truvada for 52 weeks. RESULTS: HIV-1 RNA decreased
      rapidly with treatment in all patients; first and second phase levels were lower
      in PHI patients with no appreciable difference in residual viremia between the
      two groups at 52 weeks. Episomal HIV-1 DNA increased sharply in both groups with
      peak levels at 3-4 weeks. Total HIV-1 DNA levels were reduced in both groups with
      similar kinetics, but were markedly lower in PHI patients after 52 weeks.
      Integrated HIV-1 DNA levels were significantly lower at baseline in PHI patients
      and this difference widened on treatment. Finally, total HIV-1 DNA decayed
      substantially in both groups in CTB. CONCLUSION: Treatment with raltegravir
      resulted in a large number of abrogated integration events, reflected by the
      increase of episomal HIV-1 DNA after treatment initiation. Levels of total and
      integrated HIV-1 DNA were lower in PHI patients at the end of the study period.

PMID- 21860349
TI  - Presence of headache does not influence sideline neurostatus or balance in high
      school football athletes.
AB  - OBJECTIVE: Headache is the primary self-reported symptom used to indicate
      concussion. Thus, we examined the relationship between reports of nonconcussion
      induced headache after contact sport participation and scores on common
      concussion assessment measures. DESIGN: Two-group repeated measures. SETTIN::
      Secondary school. PARTICIPANTS: One hundred five athletes from 3 area football
      teams completed a baseline evaluation. Sixteen athletes reported headaches after
      a practice/game and were compared with 16 gender-matched, age-matched, height
      matched, weight-matched, and position-matched controls. INDEPENDENT VARIABLE:
      Self-report headache. MAIN OUTCOME MEASURES: Symptom severity and endorsement
      reported on the Graded Symptoms Checklist (GSC), neurostatus measured using the
      Standard Assessment of Concussion (SAC), and postural control evaluated with the
      Balance Error Scoring System (BESS). RESULTS: Total symptom severity
      significantly increased (P < 0.01; 8.06 +/- 2.22 to 16.06 +/- 3.82) in the
      headache group and significantly decreased in the nonheadache group (P = 0.01;
      6.81 +/- 1.85 to 3.00 +/- 1.08). Symptom endorsement increased in the headache
      group (P = 0.06; 3.25 +/- 0.80 to 5.25 +/- 1.08) and significantly decreased in
      the nonheadache group (P = 0.01; 3.19 +/- 0.78 to 1.69 +/- 0.58). Both groups
      showed nonsignificant (P > 0.05) changes in SAC scores (headache, 24.75 +/- 0.73
      to 24.81 +/- 0.75; nonheadache, 24.50 +/- 0.73 to 24.87 +/- 1.20). Errors of the
      BESS significantly increased in both the groups at postgame/postpractice
      evaluation (headache, P = 0.01; 14.94 +/- 1.86 to 20.31 +/- 2.23; nonheadache, P
      < 0.01; 13.31 +/- 1.68 to 18.13 +/- 1.69). The presence of headache was
      significantly correlated with symptom reports (P > 0.05) but not SAC or BESS
      performance. CONCLUSIONS: These findings indicate that the use of headache,
      exclusively or in combination with other concussion-related symptoms, does not
      indicate performance on common concussion tools. This supports previous works,
      suggesting that clinicians must adopt a multifaceted approach to concussion
      assessment.

PMID- 21860351
TI  - Can serum soluble CD23 or CD30 predict the occurrence of lymphoma in HIV-infected
      patients?

PMID- 21860350
TI  - A broad spectrum of functional HIV-specific memory B cells in the blood of
      infected individuals with high CD4+ T-cell counts.

PMID- 21860352
TI  - Comparison of HIV-infected patients' characteristics and clinical outcomes
      between cohort-dependent and independent patients: Korean HIV cohort study.

PMID- 21860353
TI  - Long-term persistence of humoral immunity after hepatitis A vaccination in HIV
      infected adults.

PMID- 21860354
TI  - Impact of cerebrovascular disease on cognitive function in HIV-infected patients.

PMID- 21860355
TI  - Meeting the challenges of disability and HIV in East Africa.

PMID- 21860358
TI  - "Male involvement" in women and children's HIV prevention: challenges in
      definition and interpretation.

PMID- 21860357
TI  - HIV increases mean platelet volume during asymptomatic HIV infection in treatment
      naive patients.

PMID- 21860356
TI  - Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an
      HIV vaccine trial (the Step study).
AB  - INTRODUCTION: Extensive observational data suggest that herpes simplex virus type
      2 (HSV-2) infection may facilitate HIV acquisition, increase HIV viral load, and
      accelerate HIV progression and onward transmission. To explore these
      relationships, we examined the impact of preexisting HSV-2 infection in an
      international HIV vaccine trial. METHODS: We analyzed the associations between
      prevalent HSV-2 infection and HIV-1 acquisition and progression among 1836 men
      who have sex with men. We used Cox proportional hazards regression models to
      estimate the association between HSV-2 infection and both HIV acquisition and
      antiretroviral therapy (ART) initiation, and linear regression to explore the
      effect of HSV-2 on pre-ART viral load. RESULTS: HSV-2 infection increased risk of
      HIV-1 acquisition among all volunteers [adjusted hazard ratio 2.2; 95% confidence
      interval (CI): 1.4 to 3.5]. Adjusting for demographic variables, circumcision,
      Ad5 titer, and significant risk behaviors, the risk of HIV acquisition among HSV
      2-infected placebo recipients was 3-fold higher than HSV-2 seronegatives
      (adjusted hazard ratio 3.3; 95% CI: 1.6 to 6.9). Past HSV-2 infection was
      associated with a 0.2 log10 copies per milliliter higher adjusted mean set point
      viral load (95% CI: 0.3 lower to 0.6 higher). HSV-2 infection was not associated
      with time to ART initiation. CONCLUSIONS: Among men who have sex with men in an
      HIV-1 vaccine trial, preexisting HSV-2 infection was a major risk factor for HIV
      acquisition. Past HSV-2 did not significantly increase HIV viral load or early
      disease progression. HSV-2-seropositive persons will likely prove more difficult
      than HSV-2-seronegative persons to protect against HIV infection using vaccines
      or other prevention strategies.

PMID- 21860360
TI  - Scale-up and continuation of antiretroviral therapy in South African treatment
      programs, 2005-2009.

PMID- 21860361
TI  - The effect of patient load on antiretroviral treatment programmatic outcomes at
      primary health care facilities in South Africa: a multicohort study.

PMID- 21860362
TI  - The broader context of implementation science.

PMID- 21860365
TI  - Rilpivirine (Edurant)--a new drug for HIV infection.

PMID- 21860364
TI  - Azaphenanthrene alkaloids with antitumoral activity from Anaxagorea dolichocarpa
      Sprague & Sandwith (Annonaceae).
AB  - Phytochemical investigation of Anaxagorea dolichocarpa Sprague & Sandwith led to
      isolation of three azaphenanthrene alkaloids: eupolauramine, sampangine and
      imbiline 1. Their chemical structures were established on the basis of
      spectroscopic data from IR, HR-ESI-MS, NMR (including 2D experiments) and
      comparison with the literature. Sampangine and imbiline 1 are being described in
      the Anaxagorea genus for the first time. Eupolauramine and sampangine show
      concentration-dependent antitumoral activity in leukemic cells K562 with IC(50)
      of 18.97 and 10.95 ug/mL, respectively.

PMID- 21860366
TI  - Rivaroxaban (Xarelto)--a new oral anticoagulant.

PMID- 21860367
TI  - In brief: Cardiovascular safety of varenicline (Chantix).

PMID- 21860368
TI  - Drugs for peptic ulcer disease and GERD.

PMID- 21860369
TI  - Mechanisms of increased vascular superoxide production in human varicose veins.
AB  - INTRODUCTION: Varicose vein disease is one of the most common morbidities in the
      developed countries. Recent studies have shown that oxidative stress is increased
      in varicose veins (VV) and venous insufficiency. However, the exact mechanisms of
      oxidative stress in VV remain unknown. OBJECTIVES: The aim of the study was to
      measure superoxide anion production and analyze its enzymatic sources in VV in
      comparison with control human saphenous veins (HSV). Superoxide production was
      also compared between the proximal and distal segments of the veins. PATIENTS AND
      METHODS: Proximal and distal segments of varicose veins (14 patients, aged 52 +/
      3.5 years) and control veins (15 patients, aged 56 +/-4 years) were obtained
      during VV removal or elective coronary artery bypass graft surgery, respectively.
      Subjects were matched for age, sex, and the major risk factors for
      atherosclerosis. Superoxide was measured by lucigenin-enhanced chemiluminescence
      (5 MUmol/l) in the presence and absence of oxidase inhibitors. RESULTS:
      Superoxide production was increased in VV compared with control HSV. This
      increase was particularly evident in the distal segments of VV. There was a
      significant correlation between superoxide production in the proximal and distal
      segments of HSV but not of VV. Nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidases and uncoupled nitric oxide synthase (NOS) were the major sources
      of superoxide in VV, because their inhibitors greatly attenuated superoxide
      production in VV. CONCLUSIONS: NADPH oxidases and NOS could represent valuable
      drug targets for pharmacological treatment and prevention of varicose vein
      disease. Oxidative stress may provide a link between endothelial dysfunction,
      inflammation, and immune activation and the development of chronic venous
      dysfunction.

PMID- 21860370
TI  - Do circulating antibodies against C1q reflect the activity of lupus nephritis?
AB  - INTRODUCTION: The results of recent studies suggest that there is a link between
      the presence of antibodies against C1q (anti-C1q Abs) and kidney involvement in
      systemic lupus erythematosus (SLE). However, it remains unclear whether the
      clinical symptoms of lupus nephritis (LN) may be associated with the presence of
      anti-C1q Abs in serum. OBJECTIVES: The aim of the study was to compare the
      prevalence and levels of anti-C1q Abs and antibodies against double-stranded DNA
      (anti-dsDNA Abs), circulating immune complexes binding C1q (CIC-C1q), as well as
      complement components C3 and C4 in the sera of patients with LN in relation to
      the clinical activity of SLE and symptoms of LN. PATIENTS AND METHODS: The study
      involved 48 patients with LN and 66 healthy controls. Anti-dsDNA Abs, anti-C1q
      Abs, and CIC-C1q levels were determined by immunoenzymatic methods, while C3 and
      C4 by immunoturbidimetry. SLE activity was assessed using the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI). RESULTS: Anti-dsDNA Abs, anti-C1q
      Abs, and CIC-C1q were detected in 77%, 60%, and 43.7% of the patients with LN,
      respectively. The prevalence and mean levels of anti-dsDNA and anti-C1q Abs were
      significantly higher in patients with active LN than in those with inactive LN or
      controls. The levels of C3 and C4 were significantly lower in active LN than in
      inactive LN or controls. In active LN, a positive correlation between anti-C1q
      and anti-dsDNA Abs was observed. In patients with detected anti-C1q Abs,
      microhematuria (59% vs. 16%, P = 0.003), urinary casts (28% vs. 8%, P = 0.02),
      and low levels of serum C3 (P = 0.03) and C4 (P = 0.01) were observed
      statistically significantly more often. CONCLUSIONS: Simultaneous presence of
      hematuria and anti-C1q Abs may indicate an ongoing inflammatory process in the
      glomeruli in patients with SLE.

PMID- 21860371
TI  - Structure of HIV-1 capsid assemblies by cryo-electron microscopy and iterative
      helical real-space reconstruction.
AB  - Cryo-electron microscopy (cryo-EM), combined with image processing, is an
      increasingly powerful tool for structure determination of macromolecular protein
      complexes and assemblies. In fact, single particle electron microscopy and two
      dimensional (2D) electron crystallography have become relatively routine
      methodologies and a large number of structures have been solved using these
      methods. At the same time, image processing and three-dimensional (3D)
      reconstruction of helical objects has rapidly developed, especially, the
      iterative helical real-space reconstruction (IHRSR) method, which uses single
      particle analysis tools in conjunction with helical symmetry. Many biological
      entities function in filamentous or helical forms, including actin filaments,
      microtubules, amyloid fibers, tobacco mosaic viruses, and bacteria flagella, and,
      because a 3D density map of a helical entity can be attained from a single
      projection image, compared to the many images required for 3D reconstruction of a
      non-helical object, with the IHRSR method, structural analysis of such flexible
      and disordered helical assemblies is now attainable. In this video article, we
      provide detailed protocols for obtaining a 3D density map of a helical protein
      assembly (HIV-1 capsid is our example), including protocols for cryo-EM specimen
      preparation, low dose data collection by cryo-EM, indexing of helical diffraction
      patterns, and image processing and 3D reconstruction using IHRSR. Compared to
      other techniques, cryo-EM offers optimal specimen preservation under near native
      conditions. Samples are embedded in a thin layer of vitreous ice, by rapid
      freezing, and imaged in electron microscopes at liquid nitrogen temperature,
      under low dose conditions to minimize the radiation damage. Sample images are
      obtained under near native conditions at the expense of low signal and low
      contrast in the recorded micrographs. Fortunately, the process of helical
      reconstruction has largely been automated, with the exception of indexing the
      helical diffraction pattern. Here, we describe an approach to index helical
      structure and determine helical symmetries (helical parameters) from digitized
      micrographs, an essential step for 3D helical reconstruction. Briefly, we obtain
      an initial 3D density map by applying the IHRSR method. This initial map is then
      iteratively refined by introducing constraints for the alignment parameters of
      each segment, thus controlling their degrees of freedom. Further improvement is
      achieved by correcting for the contrast transfer function (CTF) of the electron
      microscope (amplitude and phase correction) and by optimizing the helical
      symmetry of the assembly.

PMID- 21860372
TI  - Measuring bacterial load and immune responses in mice infected with Listeria
      monocytogenes.
AB  - Listeria monocytogenes (Listeria) is a Gram-positive facultative intracellular
      pathogen. Mouse studies typically employ intravenous injection of Listeria, which
      results in systemic infection. After injection, Listeria quickly disseminates to
      the spleen and liver due to uptake by CD8alpha+ dendritic cells and Kupffer
      cells. Once phagocytosed, various bacterial proteins enable Listeria to escape
      the phagosome, survive within the cytosol, and infect neighboring cells. During
      the first three days of infection, different innate immune cells (e.g. monocytes,
      neutrophils, NK cells, dendritic cells) mediate bactericidal mechanisms that
      minimize Listeria proliferation. CD8+ T cells are subsequently recruited and
      responsible for the eventual clearance of Listeria from the host, typically
      within 10 days of infection. Successful clearance of Listeria from infected mice
      depends on the appropriate onset of host immune responses. There is a broad range
      of sensitivities amongst inbred mouse strains. Generally, mice with increased
      susceptibility to Listeria infection are less able to control bacterial
      proliferation, demonstrating increased bacterial load and/or delayed clearance
      compared to resistant mice. Genetic studies, including linkage analyses and
      knockout mouse strains, have identified various genes for which sequence
      variation affects host responses to Listeria infection. Determination and
      comparison of infection kinetics between different mouse strains is therefore an
      important method for identifying host genetic factors that contribute to immune
      responses against Listeria. Comparison of host responses to different Listeria
      strains is also an effective way to identify bacterial virulence factors that may
      serve as potential targets for antibiotic therapy or vaccine design. We describe
      here a straightforward method for measuring bacterial load (colony forming units
      [CFU] per tissue) and preparing single-cell suspensions of the liver and spleen
      for FACS analysis of immune responses in Listeria-infected mice. This method is
      particularly useful for initial characterization of Listeria infection in novel
      mouse strains, as well as comparison of immune responses between different mouse
      strains infected with Listeria. We use the Listeria monocytogenes EGD strain
      that, when cultured on blood agar, exhibits a characteristic halo zone around
      each colony due to beta-hemolysis (Figure 1). Bacterial load and immune responses
      can be determined at any time-point after infection by culturing tissue
      homogenate on blood agar plates and preparing tissue cell suspensions for FACS
      analysis using the protocols described below. We would note that individuals who
      are immunocompromised or pregnant should not handle Listeria, and the relevant
      institutional biosafety committee and animal facility management should be
      consulted before work commences.

PMID- 21860373
TI  - Axon stretch growth: the mechanotransduction of neuronal growth.
AB  - During pre-synaptic embryonic development, neuronal processes traverse short
      distances to reach their targets via growth cone. Over time, neuronal somata are
      separated from their axon terminals due to skeletal growth of the enlarging
      organism (Weiss 1941; Gray, Hukkanen et al. 1992). This mechanotransduction
      induces a secondary mode of neuronal growth capable of accommodating continual
      elongation of the axon (Bray 1984; Heidemann and Buxbaum 1994; Heidemann,
      Lamoureux et al. 1995; Pfister, Iwata et al. 2004). Axon Stretch Growth (ASG) is
      conceivably a central factor in the maturation of short embryonic processes into
      the long nerves and white matter tracts characteristic of the adult nervous
      system. To study ASG in vitro, we engineered bioreactors to apply tension to the
      short axonal processes of neuronal cultures (Loverde, Ozoka et al. 2011). Here,
      we detail the methods we use to prepare bioreactors and conduct ASG. First,
      within each stretching lane of the bioreactor, neurons are plated upon a micro
      manipulated towing substrate. Next, neurons regenerate their axonal processes,
      via growth cone extension, onto a stationary substrate. Finally, stretch growth
      is performed by towing the plated cell bodies away from the axon terminals
      adhered to the stationary substrate; recapitulating skeletal growth after growth
      cone extension. Previous work has shown that ASG of embryonic rat dorsal root
      ganglia neurons are capable of unprecedented growth rates up to 10mm/day,
      reaching lengths of up to 10 cm; while concurrently resulting in increased axonal
      diameters (Smith, Wolf et al. 2001; Pfister, Iwata et al. 2004; Pfister,
      Bonislawski et al. 2006; Pfister, Iwata et al. 2006; Smith 2009). This is in
      dramatic contrast to regenerative growth cone extension (in absence of mechanical
      stimuli) where growth rates average 1mm/day with successful regeneration limited
      to lengths of less than 3 cm (Fu and Gordon 1997; Pfister, Gordon et al. 2011).
      Accordingly, further study of ASG may help to reveal dysregulated growth
      mechanisms that limit regeneration in the absence of mechanical stimuli.

PMID- 21860374
TI  - Bacterial immobilization for imaging by atomic force microscopy.
AB  - AFM is a high-resolution (nm scale) imaging tool that mechanically probes a
      surface. It has the ability to image cells and biomolecules, in a liquid
      environment, without the need to chemically treat the sample. In order to
      accomplish this goal, the sample must sufficiently adhere to the mounting surface
      to prevent removal by forces exerted by the scanning AFM cantilever tip. In many
      instances, successful imaging depends on immobilization of the sample to the
      mounting surface. Optimally, immobilization should be minimally invasive to the
      sample such that metabolic processes and functional attributes are not
      compromised. By coating freshly cleaved mica surfaces with porcine (pig) gelatin,
      negatively charged bacteria can be immobilized on the surface and imaged in
      liquid by AFM. Immobilization of bacterial cells on gelatin-coated mica is most
      likely due to electrostatic interaction between the negatively charged bacteria
      and the positively charged gelatin. Several factors can interfere with bacterial
      immobilization, including chemical constituents of the liquid in which the
      bacteria are suspended, the incubation time of the bacteria on the gelatin coated
      mica, surface characteristics of the bacterial strain and the medium in which the
      bacteria are imaged. Overall, the use of gelatin-coated mica is found to be
      generally applicable for imaging microbial cells.

PMID- 21860375
TI  - An in vitro system to study tumor dormancy and the switch to metastatic growth.
AB  - Recurrence of breast cancer often follows a long latent period in which there are
      no signs of cancer, and metastases may not become clinically apparent until many
      years after removal of the primary tumor and adjuvant therapy. A likely
      explanation of this phenomenon is that tumor cells have seeded metastatic sites,
      are resistant to conventional therapies, and remain dormant for long periods of
      time. The existence of dormant cancer cells at secondary sites has been described
      previously as quiescent solitary cells that neither proliferate nor undergo
      apoptosis. Moreover, these solitary cells has been shown to disseminate from the
      primary tumor at an early stage of disease progression and reside growth-arrested
      in the patients' bone marrow, blood and lymph nodes. Therefore, understanding
      mechanisms that regulate dormancy or the switch to a proliferative state is
      critical for discovering novel targets and interventions to prevent disease
      recurrence. However, unraveling the mechanisms regulating the switch from tumor
      dormancy to metastatic growth has been hampered by the lack of available model
      systems. In vivo and ex vivo model systems to study metastatic progression of
      tumor cells have been described previously. However these model systems have not
      provided in real time and in a high throughput manner mechanistic insights into
      what triggers the emergence of solitary dormant tumor cells to proliferate as
      metastatic disease. We have recently developed a 3D in vitro system to model the
      in vivo growth characteristics of cells that exhibit either dormant (D2.OR, MCF7,
      K7M2-AS.46) or proliferative (D2A1, MDA-MB-231, K7M2) metastatic behavior in
      vivo. We demonstrated that tumor cells that exhibit dormancy in vivo at a
      metastatic site remain quiescent when cultured in a 3-dimension (3D) basement
      membrane extract (BME), whereas cells highly metastatic in vivo readily
      proliferate in 3D culture after variable, but relatively short periods of
      quiescence. Importantly by utilizing the 3D in vitro model system we demonstrated
      for the first time that the ECM composition plays an important role in regulating
      whether dormant tumor cells will switch to a proliferative state and have
      confirmed this in in vivo studies. Hence, the model system described in this
      report provides an in vitro method to model tumor dormancy and study the
      transition to proliferative growth induced by the microenvironment.

PMID- 21860377
TI  - Mammary transplantation of stromal cells and carcinoma cells in C57BL/6J mice.
AB  - The influence of stromal cells, including fibroblasts on mammary tumor
      progression has been well documented through the use of mouse models, in
      particular through transplantation of stromal cells and epithelial cells in the
      mammary gland of mice. Current transplantation models often involve the use of
      immunocompromised mice due to the different genetic backgrounds of stromal cells
      and epithelial cells. Extracellular matrices are often used to embed the two
      different cell types for consistent cell-cell interactions, but involve the use
      of Matrigel or rat tail collagen, which are immunogenic substrates. The lack of
      functional T cells from immunocompromised mice prevents accurate assessment of
      stromal cells on mammary tumor progression in vivo, with important implications
      on drug development and efficacy. Moreover, immunocompromised mice are costly,
      hard to breed and require special care conditions. To overcome these obstacles,
      we have developed an approach to orthotopically transplant stromal cell and
      epithelial cells into mice from the same genetic background to induce consistent
      tumor formation. This system involves harvesting normal, carcinoma associated
      fibroblasts, PyVmT mammary carcinoma cells and collagen from donor C57BL/6J mice.
      The cells are then embedded in collagen and transplanted in the inguinal mammary
      glands of female C57BL/6J mice. Transplantation of PyVmT cells alone form
      palpable tumors 30-40 days post transplantation. Endpoint analysis at 60 days
      indicates that co-transplantation with fibroblasts enhances mammary tumor growth
      compared to PyVmT cells transplanted alone. While cells and matrix from C57BL/6J
      mice were used in these studies, the isolation of cells and matrix and
      transplantation approach may be applied towards mice from different genetic
      backgrounds demonstrating versatility. In summary, this system may be used to
      investigate molecular interactions between stromal cells and epithelial cells,
      and overcomes critical limitations in immunocompromised mouse models.

PMID- 21860376
TI  - Competitive genomic screens of barcoded yeast libraries.
AB  - By virtue of advances in next generation sequencing technologies, we have access
      to new genome sequences almost daily. The tempo of these advances is
      accelerating, promising greater depth and breadth. In light of these
      extraordinary advances, the need for fast, parallel methods to define gene
      function becomes ever more important. Collections of genome-wide deletion mutants
      in yeasts and E. coli have served as workhorses for functional characterization
      of gene function, but this approach is not scalable, current gene-deletion
      approaches require each of the thousands of genes that comprise a genome to be
      deleted and verified. Only after this work is complete can we pursue high
      throughput phenotyping. Over the past decade, our laboratory has refined a
      portfolio of competitive, miniaturized, high-throughput genome-wide assays that
      can be performed in parallel. This parallelization is possible because of the
      inclusion of DNA 'tags', or 'barcodes,' into each mutant, with the barcode
      serving as a proxy for the mutation and one can measure the barcode abundance to
      assess mutant fitness. In this study, we seek to fill the gap between DNA
      sequence and barcoded mutant collections. To accomplish this we introduce a
      combined transposon disruption-barcoding approach that opens up parallel barcode
      assays to newly sequenced, but poorly characterized microbes. To illustrate this
      approach we present a new Candida albicans barcoded disruption collection and
      describe how both microarray-based and next generation sequencing-based platforms
      can be used to collect 10,000-1,000,000 gene-gene and drug-gene interactions in a
      single experiment.

PMID- 21860378
TI  - Induction and testing of hypoxia in cell culture.
AB  - Hypoxia is defined as the reduction or lack of oxygen in organs, tissues, or
      cells. This decrease of oxygen tension can be due to a reduced supply in oxygen
      (causes include insufficient blood vessel network, defective blood vessel, and
      anemia) or to an increased consumption of oxygen relative to the supply (caused
      by a sudden higher cell proliferation rate). Hypoxia can be physiologic or
      pathologic such as in solid cancers, rheumatoid arthritis, atherosclerosis etc...
      Each tissues and cells have a different ability to adapt to this new condition.
      During hypoxia, hypoxia inducible factor alpha (HIF) is stabilized and regulates
      various genes such as those involved in angiogenesis or transport of oxygen. The
      stabilization of this protein is a hallmark of hypoxia, therefore detecting HIF
      is routinely used to screen for hypoxia. In this article, we propose two simple
      methods to induce hypoxia in mammalian cell cultures and simple tests to evaluate
      the hypoxic status of these cells.

PMID- 21860379
TI  - High throughput screening of fungal endoglucanase activity in Escherichia coli.
AB  - Cellulase enzymes (endoglucanases, cellobiohydrolases, and beta-glucosidases)
      hydrolyze cellulose into component sugars, which in turn can be converted into
      fuel alcohols. The potential for enzymatic hydrolysis of cellulosic biomass to
      provide renewable energy has intensified efforts to engineer cellulases for
      economical fuel production. Of particular interest are fungal cellulases, which
      are already being used industrially for foods and textiles processing.
      Identifying active variants among a library of mutant cellulases is critical to
      the engineering process; active mutants can be further tested for improved
      properties and/or subjected to additional mutagenesis. Efficient engineering of
      fungal cellulases has been hampered by a lack of genetic tools for native
      organisms and by difficulties in expressing the enzymes in heterologous hosts.
      Recently, Morikawa and coworkers developed a method for expressing in E. coli the
      catalytic domains of endoglucanases from H. jecorina, an important industrial
      fungus with the capacity to secrete cellulases in large quantities. Functional E.
      coli expression has also been reported for cellulases from other fungi, including
      Macrophomina phaseolina and Phanerochaete chrysosporium. We present a method for
      high throughput screening of fungal endoglucanase activity in E. coli. This
      method uses the common microbial dye Congo Red (CR) to visualize enzymatic
      degradation of carboxymethyl cellulose (CMC) by cells growing on solid medium.
      The activity assay requires inexpensive reagents, minimal manipulation, and gives
      unambiguous results as zones of degradation ("halos") at the colony site.
      Although a quantitative measure of enzymatic activity cannot be determined by
      this method, we have found that halo size correlates with total enzymatic
      activity in the cell. Further characterization of individual positive clones will
      determine , relative protein fitness. Traditional bacterial whole cell CMC/CR
      activity assays involve pouring agar containing CMC onto colonies, which is
      subject to cross-contamination, or incubating cultures in CMC agar wells, which
      is less amenable to large-scale experimentation. Here we report an improved
      protocol that modifies existing wash methods for cellulase activity: cells grown
      on CMC agar plates are removed prior to CR staining. Our protocol significantly
      reduces cross-contamination and is highly scalable, allowing the rapid screening
      of thousands of clones. In addition to H. jecorina enzymes, we have expressed and
      screened endoglucanase variants from the Thermoascus aurantiacus and Penicillium
      decumbens, suggesting that this protocol is applicable to enzymes from a range of
      organisms.

PMID- 21860380
TI  - Protein membrane overlay assay: a protocol to test interaction between soluble
      and insoluble proteins in vitro.
AB  - Validating interactions between different proteins is vital for investigation of
      their biological functions on the molecular level. There are several methods,
      both in vitro and in vivo, to evaluate protein binding, and at least two methods
      that complement the shortcomings of each other should be conducted to obtain
      reliable insights. For an in vivo assay, the bimolecular fluorescence
      complementation (BiFC) assay represents the most popular and least invasive
      approach that enables to detect protein-protein interaction within living cells,
      as well as identify the intracellular localization of the interacting proteins.
      In this assay, non-fluorescent N- and C-terminal halves of GFP or its variants
      are fused to tested proteins, and when the two fusion proteins are brought
      together due to the tested proteins' interactions, the fluorescent signal is
      reconstituted. Because its signal is readily detectable by epifluorescence or
      confocal microscopy, BiFC has emerged as a powerful tool of choice among cell
      biologists for studying about protein-protein interactions in living cells. This
      assay, however, can sometimes produce false positive results. For example, the
      fluorescent signal can be reconstituted by two GFP fragments arranged as far as 7
      nm from each other due to close packing in a small subcellular compartment,
      rather that due to specific interactions. Due to these limitations, the results
      obtained from live cell imaging technologies should be confirmed by an
      independent approach based on a different principle for detecting protein
      interactions. Co-immunoprecipitation (Co-IP) or glutathione transferase (GST)
      pull-down assays represent such alternative methods that are commonly used to
      analyze protein-protein interactions in vitro. However, iIn these assays,
      however, the tested proteins must be readily soluble in the buffer that
      supportsused for the binding reaction. Therefore, specific interactions involving
      an insoluble protein cannot be assessed by these techniques. Here, we illustrate
      the protocol for the protein membrane overlay binding assay, which circumvents
      this difficulty. In this technique, interaction between soluble and insoluble
      proteins can be reliably tested because one of the proteins is immobilized on a
      membrane matrix. This method, in combination with in vivo experiments, such as
      BiFC, provides a reliable approach to investigate and characterize interactions
      faithfully between soluble and insoluble proteins. In this article, binding
      between Tobacco mosaic virus (TMV) movement protein (MP), which exerts multiple
      functions during viral cell-to-cell transport, and a recently identified plant
      cellular interactor, tobacco ankyrin repeat-containing protein (ANK), is
      demonstrated using this technique.

PMID- 21860381
TI  - Targeting olfactory bulb neurons using combined in vivo electroporation and Gal4
      based enhancer trap zebrafish lines.
AB  - In vivo electroporation is a powerful method for delivering DNA expression
      plasmids, RNAi reagents, and morpholino anti-sense oligonucleotides to specific
      regions of developing embryos, including those of C. elegans, chick, Xenopus,
      zebrafish, and mouse. In zebrafish, in vivo electroporation has been shown to
      have excellent spatial and temporal resolution for the delivery of these
      reagents. The temporal resolution of this method is important because it allows
      for incorporation of these reagents at specific stages in development.
      Furthermore, because expression from electroporated vectors occurs within 6
      hours, this method is more timely than transgenic approaches. While the spatial
      resolution can be extremely precise when targeting a single cell, it is often
      preferable to incorporate reagents into a specific cell population within a
      tissue or structure. When targeting multiple cells, in vivo electroporation is
      efficient for delivery to a specific region of the embryo; however, particularly
      within the developing nervous system, it is difficult to target specific cell
      types solely through spatially discrete electroporation. Alternatively, enhancer
      trap transgenic lines offer excellent cell type-specific expression of
      transgenes. Here we describe an approach that combines transgenic Gal4-based
      enhancer trap lines with spatially discrete in vivo electroporation to
      specifically target developing neurons of the zebrafish olfactory bulb. The
      Et(zic4:Gal4TA4,UAS:mCherry)(hzm5) (formerly GA80_9) enhancer trap line
      previously described, displays targeted transgenic expression of mCherry mediated
      by a zebrafish optimized Gal4 (KalTA4) transcriptional activator in multiple
      regions of the developing brain including hindbrain, cerebellum, forebrain, and
      the olfactory bulb. To target GFP expression specifically to the olfactory bulb,
      a plasmid with the coding sequence of GFP under control of multiple Gal4 binding
      sites (UAS) was electroporated into the anterior end of the forebrain at 24-28
      hours post-fertilization (hpf). Although this method incorporates plasmid DNA
      into multiple regions of the forebrain, GFP expression is only induced in cells
      transgenically expressing the KalTA4 transcription factor. Thus, by using the
      GA080_9 transgenic line, this approach led to GFP expression exclusively in the
      developing olfactory bulb. GFP expressing cells targeted through this approach
      showed typical axonal projections, as previously described for mitral cells of
      the olfactory bulb. This method could also be used for targeted delivery of other
      reagents including short-hairpin RNA interference expression plasmids, which
      would provide a method for spatially and temporally discrete loss-of-function
      analysis.

PMID- 21860387
TI  - Metabolic regulation by ERK.

PMID- 21860382
TI  - Mouse in utero electroporation: controlled spatiotemporal gene transfection.
AB  - In order to understand the function of genes expressed in specific region of the
      developing brain, including signaling molecules and axon guidance molecules,
      local gene transfer or knock- out is required. Gene targeting knock-in or knock
      out into local regions is possible to perform with combination with a specific
      CRE line, which is laborious, costly, and time consuming. Therefore, a simple
      transfection method, an in utero electroporation technique, which can be
      performed with short time, will be handy to test the possible function of
      candidate genes prior to the generation of transgenic animals. In addition to
      this, in utero electroporation targets areas of the brain where no specific CRE
      line exists, and will limit embryonic lethality. Here, we present a method of in
      utero electroporation combining two different types of electrodes for simple and
      convenient gene transfer into target areas of the developing brain. First, a
      unique holding method of embryos using an optic fiber optic light cable will make
      small embryos (from E9.5) visible for targeted DNA solution injection into
      ventricles and needle type electrodes insertion to the targeted brain area. The
      patterning of the brain such as cortical area occur at early embryonic stage,
      therefore, these early electroporation from E9.5 make a big contribution to
      understand entire area patterning event. Second, the precise shape of a capillary
      prevents uterine damage by making holes by insertion of the capillary.
      Furthermore, the precise shape of the needle electrodes are created with tungsten
      and platinum wire and sharpened using sand paper and insulated with nail polish,
      a method which is described in great detail in this protocol. This unique
      technique allows transfection of plasmid DNA into restricted areas of the brain
      and will enable small embryos to be electroporated. This will help to, open a new
      window for many scientists who are working on cell differentiation, cell
      migration, axon guidance in very early embryonic stage. Moreover, this technique
      will allow scientists to transfect plasmid DNA into deep parts of the developing
      brain such as thalamus and hypothalamus, where not many region-specific CRE lines
      exist for gain of function (GOF) or loss of function (LOF) analyses.

PMID- 21860390
TI  - JH2 is active!

PMID- 21860391
TI  - Molecular control of endothelial cell behaviour during blood vessel
      morphogenesis.
AB  - The vertebrate vasculature forms an extensive branched network of blood vessels
      that supplies tissues with nutrients and oxygen. During vascular development,
      coordinated control of endothelial cell behaviour at the levels of cell
      migration, proliferation, polarity, differentiation and cell-cell communication
      is critical for functional blood vessel morphogenesis. Recent data uncover
      elaborate transcriptional, post-transcriptional and post-translational mechanisms
      that fine-tune key signalling pathways (such as the vascular endothelial growth
      factor and Notch pathways) to control endothelial cell behaviour during blood
      vessel sprouting (angiogenesis). These emerging frameworks controlling
      angiogenesis provide unique insights into fundamental biological processes common
      to other systems, such as tissue branching morphogenesis, mechanotransduction and
      tubulogenesis.

PMID- 21860394
TI  - Dissecting our impact factor.

PMID- 21860400
TI  - Spintronics: Taming spin currents.

PMID- 21860393
TI  - The predator becomes the prey: regulating the ubiquitin system by ubiquitylation
      and degradation.
AB  - Ubiquitylation (also known as ubiquitination) regulates essentially all of the
      intracellular processes in eukaryotes through highly specific modification of
      numerous cellular proteins, which is often tightly regulated in a spatial and
      temporal manner. Although most often associated with proteasomal degradation,
      ubiquitylation frequently serves non-proteolytic functions. In light of its
      central roles in cellular regulation, it has not been surprising to find that
      many of the components of the ubiquitin system itself are regulated by
      ubiquitylation. This observation has broad implications for pathophysiology.

PMID- 21860401
TI  - Solid electrolytes: Lithium ions on the fast track.

PMID- 21860392
TI  - Deconstructing the skin: cytoarchitectural determinants of epidermal
      morphogenesis.
AB  - To provide a stable environmental barrier, the epidermis requires an integrated
      network of cytoskeletal elements and cellular junctions. Nevertheless, the
      epidermis ranks among the body's most dynamic tissues, continually regenerating
      itself and responding to cutaneous insults. As keratinocytes journey from the
      basal compartment towards the cornified layers, they completely reorganize their
      adhesive junctions and cytoskeleton. These architectural components are more than
      just rivets and scaffolds - they are active participants in epidermal
      morphogenesis that regulate epidermal polarization, signalling and barrier
      formation.

PMID- 21860402
TI  - Material witness: Caged water.

PMID- 21860403
TI  - Graphene nanoribbons: Twisted within nanotubes.

PMID- 21860404
TI  - Metallic alloys: All particles are equal.

PMID- 21860405
TI  - Heterogeneity of aberrant immunoglobulin expression in cancer cells.
AB  - Accumulating evidence has shown that immunoglobulin (Ig) is 'unexpectedly'
      expressed by epithelial cancer cells and that it can promote tumor growth. The
      main purpose of this study was to explore the components of the cancerous Ig and
      its possible function. The presence of cancerous Ig in the Golgi apparatus was
      confirmed by immunofluorescence, indirectly suggesting that the cancerous Ig was
      processed and packaged in cancer cells. Western blot analysis and ELISA results
      indicated that cancer cells produced membrane Ig and secreted Ig into the
      supernatant fraction. The cancerous Ig consists of an alpha heavy chain and a
      kappa light chain. Finally, by analyzing the Ig components pulled down by protein
      A beads, the cancerous Ig was found to be structurally distinct from normal Ig.
      The cancerous Ig was truncated or aberrant. Although the underlying mechanism
      that causes the abnormalities has not been determined, our current discoveries
      strengthen our previous findings and promise fruitful future explorations.

PMID- 21860406
TI  - Novel insights into the molecular mechanisms of alpha-fetoprotein expression and
      malignant phenotypes of hepatocellular carcinoma.

PMID- 21860407
TI  - MicroRNA immunobiology: when microRNA chemists meet immunologists.

PMID- 21860408
TI  - SHP limits TLR signaling, an inducible transcriptional corepressor.

PMID- 21860409
TI  - Construct validity in a high-fidelity prostate exam simulator.
AB  - BACKGROUND: All health care practitioners should be facile in the digital rectal
      exam (DRE) as it provides prostate, rectal and neurological information. The
      purpose of this study was first to justify our hypothesis that tissue elasticity
      is indicative of carcinomatous changes. Second, we employed urological surgeons
      to evaluate our prostate simulator in three ways: (1) authenticate that the
      elasticity of the simulated prostates accurately represents the range of normal
      prostate stiffness, (2) determine the range of nodule size reasonably palpable by
      DRE and (3) discern what degree of elasticity difference within the same prostate
      suggests malignancy. METHODS: Institutional Review Board-approved materials
      characterization, human-subjects experiments, histopathology and chart
      abstraction of clinical history were performed. Material characterization of 21
      ex-vivo prostatectomy specimens was evaluated using a custom-built, portable
      spherical indentation device while a novel prostate simulator was employed to
      measure human-subject perception of prostatic state. RESULTS: From the materials
      characterization, the measurements of the 21 gross prostates and 40 cross
      sections yielded 306 data points. Within the same prostate, cancer was always
      stiffer. Of the seven cases with an abnormal DRE, the DRE accurately identified
      adenocarcinoma in 85%. From the human-subjects experiments, the simulated
      prostates evaluated by urologists ranged in stiffness from 8.9 to 91 kPa,
      mimicking the range found on ex vivo analysis of 4.6-236.7 kPa. The urological
      surgeons determined the upper limit of stiffness palpated as realistic for a
      healthy prostate was 59.63 kPa while the lower limit of stiffness was 27.1 kPa.
      Nodule size less than 7.5 mm was felt to be too small to reasonably palpate.
      CONCLUSIONS: We found it is not the absolute elasticity of the nodule, but rather
      the relationship of the nodule with the background prostate elasticity that
      constitutes the critical tactile feedback. Prostate simulator training may lead
      to greater familiarity with pertinent diagnostic cues and diagnosis of prostate
      cancer.

PMID- 21860410
TI  - HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular
      metastasis of hypoxic breast cancer cells to the lungs.
AB  - Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa
      cells must intravasate through endothelial cells (ECs) to enter a blood vessel in
      the primary tumor and then adhere to ECs and extravasate at the metastatic site.
      In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF)
      activity in BrCa cells by RNA interference or digoxin treatment inhibits primary
      tumor growth and also inhibits the metastasis of BrCa cells to the lungs by
      blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion
      molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction,
      whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with
      HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to
      the lungs.

PMID- 21860411
TI  - Molecular chaperone complexes with antagonizing activities regulate stability and
      activity of the tumor suppressor LKB1.
AB  - LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone
      condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a
      sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a
      serine/threonine kinase that associates with the pseudokinase STRAD (STE-20
      related pseudokinase) and the scaffolding protein MO25, the formation of this
      heterotrimeric complex promotes allosteric activation of LKB1. We have previously
      reported that the molecular chaperone heat shock protein 90 (Hsp90) binds to and
      stabilizes LKB1. Combining pharmacological studies and RNA interference
      approaches, we now provide evidence that the co-chaperone Cdc37 participates to
      the regulation of LKB1 stability. It is known that the Hsp90-Cdc37 complex
      recognizes a surface within the N-terminal catalytic lobe of client protein
      kinases. In agreement with this finding, we found that the chaperones Hsp90 and
      Cdc37 interact with an LKB1 isoform that differs in the C-terminal region, but
      not with a novel LKB1 variant that lacks a portion of the kinase N-terminal lobe
      domain. Reconstitution of the two complexes LKB1-STRAD and LKB1-Hsp90-Cdc37 with
      recombinant proteins revealed that the former is catalytically active whereas the
      latter is inactive. Furthermore, consistent with a documented repressor function
      of Hsp90, LKB1 kinase activity was transiently stimulated upon dissociation of
      Hsp90. Finally, disruption of the LKB1-Hsp90 complex favors the recruitment of
      both Hsp/Hsc70 and the U-box dependent E3 ubiquitin ligase CHIP (carboxyl
      terminus of Hsc70-interacting protein) that triggers LKB1 degradation. Taken
      together, our results establish that the Hsp90-Cdc37 complex controls both the
      stability and activity of the LKB1 kinase. This study further shows that two
      chaperone complexes with antagonizing activities, Hsp90-Cdc37 and Hsp/Hsc70-CHIP,
      finely control the cellular level of LKB1 protein.

PMID- 21860413
TI  - Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation.
AB  - The c-Jun transcription factor is a highly unstable oncoprotein. Several
      ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized
      once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or
      other protein kinases. This phosphorylation decreases c-Jun ubiquitination and
      degradation. The underlying mechanism for this phenomenon is still unknown. Here,
      we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and
      ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N
      terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7,
      which leads to increased stabilization and accumulation of c-Jun. These results
      reveal that Rack1 has a very important role in tumorigenesis by maintaining the
      stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or
      other kinases.

PMID- 21860414
TI  - Cilia, adenomatous polyposis coli and associated diseases.
AB  - Cilium is a conservative cell organelle, found in many types of cell surfaces.
      Cilia are tail-like prominence protruding out of the cell surface, capable of
      locomotion and acting as the cell's signal transduction sensory organs with their
      complex structures and ingenious function. Studies have shown that ciliary
      pathological changes and defects are related to the development of many diseases,
      including renal cysts, infertility, organ reversal, obesity and so on. The
      inactivation and mutation of cilia-related proteins can cause tumors, such as
      neoplasms, intestinal cancer, myeloma, rhabdomyosarcoma and adenocarcinoma.
      Adenomatous polyposis coli (APC) is a kind of multifunctional protein encoded by
      the APC gene that participates in many vital activities of organisms. The
      mutation of APC can lead to familial adenomatous polyposis, and also has a role
      in the development of human tumors, such as gastric cancer, esophageal cancer and
      breast carcinoma. Recent studies indicate that the abnormal mutation of APC may
      lead to some diseases caused by abnormal growth of cilia. Herein, the development
      of studies on cilia, APC and associated diseases are summarized in brief.

PMID- 21860412
TI  - DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer.
AB  - MicroRNAs (miRNAs) are recognized as being central players in many biological
      processes and cellular pathways. Their roles in disease have been highlighted
      first by observation of their aberrant expression profiles in human tumors, and
      then by in vitro and in vivo functional studies in transformed cells and model
      organisms. One of the most commonly observed features of miRNAs in malignancies
      is a defect in their production. Although several causes may be associated with
      this phenomenon, such as upstream oncogenic/tumor-suppressor defects and
      alterations in the miRNA-processing machinery, epigenetic inactivation is the
      prime suspect. The number of miRNAs with putative growth-inhibitory functions
      undergoing promoter CpG island hypermethylation in human cancer is growing fast
      and more detailed biological studies are necessary. The recognition of miR-124a
      and miR-34b/c as bona fide tumor-suppressor miRNAs undergoing DNA methylation
      associated silencing in a wide spectrum of human neoplasms is a good starting
      point to be followed by other candidate miRNAs. Most importantly, even at this
      early stage, the transcriptional repression of miRNAs by hypermethylation of
      their corresponding promoter loci seems to be a common feature of all human
      tumors. This will have translational consequences for the management of the
      disease.

PMID- 21860415
TI  - Macrophage-elicited loss of estrogen receptor-alpha in breast cancer cells via
      involvement of MAPK and c-Jun at the ESR1 genomic locus.
AB  - Estrogen receptor-alpha (ERalpha, ESR1) is a pivotal transcriptional regulator of
      breast cancer physiology and is targeted by endocrine therapies. Loss of ERalpha
      activity or expression is an indication of endocrine resistance and is associated
      with increased risk of tumor recurrence and worse prognosis. In this study, we
      sought to investigate whether elements of the tumor microenvironment, namely
      macrophages, would impact on ERalpha and we found that macrophage-derived factors
      caused loss of ERalpha expression in breast cancer cells. Conditioned media from
      macrophages caused activation of several intracellular pathways in breast cancer
      cells of which c-Src, protein kinase c and mitogen-activated protein kinase
      (MAPK) were essential for loss of ERalpha expression. Moreover, a prolonged
      hyperactivation of MAPK was observed. The activation of this kinase cascade
      resulted in recruitment of extracellular signal regulated kinase 2 (ERK2)
      directly to chromatin at the ESR1 gene locus in a process that was dependent upon
      activation and recruitment of the c-Jun transcription factor. Thus, we identify a
      novel mechanism for loss of ERalpha expression in breast cancer cells via
      macrophage activation of kinase cascades in the cancer cells causing
      transcriptional repression of the ESR1 gene by a direct chromatin action of a c
      Jun/ERK2 complex. The findings in this study support an alternative mechanism,
      not intrinsic to the tumor cell but derived from the cross-talk with the tumor
      microenvironment, that could lead to endocrine resistance and might be targeted
      therapeutically to prevent loss of ERalpha expression in breast tumors.

PMID- 21860416
TI  - A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte
      transformation and promoting melanoma growth.
AB  - Malignant melanoma is the most aggressive form of skin cancer and its incidence
      has doubled in the last two decades. It represents only 4% of skin cancer cases
      per year, but causes as many as 74% of skin cancer deaths. Early detection of
      malignant melanoma is associated with survival rates of up to 90%, but later
      detection (stage III to stage IV) is associated with survival rates of only 10%.
      Dysregulation of microRNA (miRNA) expression has been linked to tumor development
      and progression by functioning either as a tumor suppressor, an oncogene or a
      metastasis regulator in multiple cancer types. To understand the role of miRNA in
      the pathogenesis of malignant melanoma and identify biomarkers of metastasis,
      miRNA expression profiles in skin punches from 33 metastatic melanoma patients
      and 14 normal healthy donors were compared. We identified a cluster of 14 miRNAs
      on the X chromosome, termed the miR-506-514 cluster, which was consistently
      overexpressed in nearly all melanomas tested (30-60 fold, P<0.001), regardless of
      mutations in N-ras or B-raf. Inhibition of the expression of this cluster as a
      whole, or one of its sub-clusters (Sub-cluster A) consisting of six mature
      miRNAs, led to significant inhibition of cell growth, induction of apoptosis,
      decreased invasiveness and decreased colony formation in soft agar across
      multiple melanoma cell lines. Sub-cluster A of the miR-506-514 cluster was
      critical for maintaining the cancer phenotype, but the overexpression of the full
      cluster was necessary for melanocyte transformation. Our results provide new
      insights into the functional role of this miRNA cluster in melanoma, and suggest
      new approaches to treat or diagnose this disease.

PMID- 21860417
TI  - Loss of LIN9, a member of the DREAM complex, cooperates with SV40 large T antigen
      to induce genomic instability and anchorage-independent growth.
AB  - The DREAM complex is an important regulator of mitotic gene expression during the
      cell cycle. Here we report that inactivation of LIN9, a subunit of DREAM, results
      in premature senescence, which can be overcome by the SV40 large T (LT) antigen.
      Together with the observation that p16(INK4a) and p21(Waf1) are upregulated upon
      loss of LIN9, these results indicate that senescence is triggered by the pRB and
      p53 tumor suppressor pathways. We also find that LIN9-null cells that escape
      senescence are chromosomally instable because of compromised mitotic fidelity.
      SV40 LT-expressing cells that adapt to the loss of LIN9 can grow anchorage
      independently in soft agar, a hallmark of oncogenic transformation. Taken
      together, these results suggest an important role of mitotic gene regulation in
      the maintenance of genomic stability and tumor suppression.

PMID- 21860418
TI  - Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy
      response in acute myeloid leukemia.
AB  - The wild-type tumor-suppressor gene TP53 encodes several isoforms of the p53
      protein. However, while the role of p53 in controlling normal cell cycle
      progression and tumor suppression is well established, the clinical significance
      of p53 isoform expression is unknown. A novel bioinformatic analysis of p53
      isoform expression in 68 patients with acute myeloid leukemia revealed distinct
      p53 protein biosignatures correlating with clinical outcome. Furthermore, we show
      that mutated FLT3, a prognostic marker for short survival in AML, is associated
      with expression of full-length p53. In contrast, mutated NPM1, a prognostic
      marker for long-term survival, correlated with p53 isoforms beta and gamma
      expression. In conclusion, p53 biosignatures contain useful information for
      cancer evaluation and prognostication.

PMID- 21860419
TI  - FOXO3a represses VEGF expression through FOXM1-dependent and -independent
      mechanisms in breast cancer.
AB  - Vascular endothelial growth factor (VEGF) has a central role in breast cancer
      development and progression, but the mechanisms that control its expression are
      poorly understood. Breast cancer tissue microarrays revealed an inverse
      correlation between the Forkhead transcription factor Forkhead box class O
      (FOXO)3a and VEGF expression. Using the lapatinib-sensitive breast cancer cell
      lines BT474 and SKBR3 as model systems, we tested the possibility that VEGF
      expression is negatively regulated by FOXO3a. Lapatinib treatment of BT474 or
      SKBR3 cells resulted in nuclear translocation and activation of FOXO3a, followed
      by a reduction in VEGF expression. Transient transfection and inducible
      expression experiments showed that FOXO3a represses the proximal VEGF promoter,
      whereas another Forkhead member, FOXM1, induces VEGF expression. Chromatin
      immunoprecipitation and oligonucleotide pull-down assays showed that both FOXO3a
      and FOXM1 bind a consensus Forkhead response element (FHRE) in the VEGF promoter.
      Upon lapatinib stimulation, activated FOXO3a displaces FOXM1 bound to the FHRE
      before recruiting histone deacetylase 2 (HDAC2) to the promoter, leading to
      decreased histones H3 and H4 acetylation, and concomitant transcriptional
      inhibition of VEGF. These results show that FOXO3a-dependent repression of target
      genes in breast cancer cells, such as VEGF, involves competitive displacement of
      DNA-bound FOXM1 and active recruitment of transcriptional repressor complexes.

PMID- 21860420
TI  - Cellular features of senescence during the evolution of human and murine ductal
      pancreatic cancer.
AB  - During tumor initiation, oncogene-induced senescence (OIS) is proposed to limit
      the progression of preneoplasms to invasive carcinoma unless circumvented by the
      acquisition of certain tumor suppressor mutations. Using a variety of biomarkers,
      OIS has been previously reported in a wide range of human and murine precursor
      lesions, including the pancreas, lung, colon and skin. Here, we have
      characterized a panel of potential OIS biomarkers in human and murine pancreatic
      intraepithelial neoplasia (PanIN), and found that only senescence-associated beta
      galactosidase (SAbetagal) activity is specifically enriched in these precursors,
      compared with pancreatic ductal adenocarcinoma (PDA). Indeed, many of the other
      proposed OIS biomarkers are detected in actively proliferating PanIN epithelium
      and in cells within the microenvironment. Surprisingly, acinar to ductal
      metaplasia (ADM), a distinct preneoplasm that is potentially a precursor for
      PanIN, also exhibits SAbetagal activity and contains a higher content of p21 and
      p53 than PanIN. Therefore, SAbetagal activity is the only biomarker that
      accurately identifies a small and heterogeneous population of non-proliferating
      premalignant cells in the pancreas, and the concomitant expression of p53 and p21
      in ADM supports the possibility that PanIN and ADM each exhibit discrete
      senescence blocks.

PMID- 21860421
TI  - Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in
      neuroblastoma.
AB  - Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q
      with a shortest region of overlap in the 11q23 region. These deletions are
      thought to cause inactivation of tumor suppressor genes leading to
      haploinsufficiency. Alternatively, micro-deletions could lead to gene fusion
      products that are tumor driving. To identify such events we analyzed a series of
      neuroblastomas by comparative genomic hybridization and single-nucleotide
      polymorphism arrays and integrated these data with Affymetrix mRNA profiling data
      with the bioinformatic tool R2 (http://r2.amc.nl). We identified three
      neuroblastoma samples with small interstitial deletions at 11q23, upstream of the
      forkhead-box R1 transcription factor (FOXR1). Genes at the proximal side of the
      deletion were fused to FOXR1, resulting in fusion transcripts of MLL-FOXR1 and
      PAFAH1B2-FOXR1. FOXR1 expression has only been detected in early embryogenesis.
      Affymetrix microarray analysis showed high FOXR1 mRNA expression exclusively in
      the neuroblastomas with micro-deletions and rare cases of other tumor types,
      including osteosarcoma cell line HOS. RNAi silencing of FOXR1 strongly inhibited
      proliferation of HOS cells and triggered apoptosis. Expression profiling of these
      cells and reporter assays suggested that FOXR1 is a negative regulator of fork
      head box factor-mediated transcription. The neural crest stem cell line JoMa1
      proliferates in culture conditional to activity of a MYC-ER transgene. Over
      expression of the wild-type FOXR1 could functionally replace MYC and drive
      proliferation of JoMa1. We conclude that FOXR1 is recurrently activated in
      neuroblastoma by intrachromosomal deletion/fusion events, resulting in
      overexpression of fusion transcripts. Forkhead-box transcription factors have not
      been previously implicated in neuroblastoma pathogenesis. Furthermore, this is
      the first identification of intrachromosomal fusion genes in neuroblastoma.

PMID- 21860422
TI  - Genome-wide mapping of Myc binding and gene regulation in serum-stimulated
      fibroblasts.
AB  - The transition from quiescence to proliferation is a key regulatory step that can
      be induced by serum stimulation in cultured fibroblasts. The transcription factor
      Myc is directly induced by serum mitogens and drives a secondary gene expression
      program that remains largely unknown. Using mRNA profiling, we identify close to
      300 Myc-dependent serum response (MDSR) genes, which are induced by serum in a
      Myc-dependent manner in mouse fibroblasts. Mapping of genomic Myc-binding sites
      by ChIP-seq technology revealed that most MDSR genes were directly targeted by
      Myc, but represented a minor fraction (5.5%) of all Myc-bound promoters (which
      were 22.4% of all promoters). Other target loci were either induced by serum in a
      Myc-independent manner, were not significantly regulated or were negatively
      regulated. MDSR gene products were involved in a variety of processes, including
      nucleotide biosynthesis, ribosome biogenesis, DNA replication and RNA control. Of
      the 29 MDSR genes targeted by RNA interference, three showed a requirement for
      cell-cycle entry upon serum stimulation and 11 for long-term proliferation and/or
      survival. Hence, proper coordination of key regulatory and biosynthetic pathways
      following mitogenic stimulation relies upon the concerted regulation of multiple
      Myc-dependent genes.

PMID- 21860423
TI  - Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate
      cancer cells.
AB  - PIM1 kinase and MYC are commonly co-expressed in human prostate cancer and
      synergize to induce rapidly progressing prostate cancer in mouse models.
      Deficiency of the Pim kinase genes is well tolerated in vivo, suggesting that
      PIM1 inhibition might offer an attractive therapeutic modality for prostate
      cancer, particularly for MYC-expressing tumors. Here we examine the molecular
      consequences of Pim1 and MYC overexpression in the prostate as well as the
      effects of depleting Pim1 in prostate carcinoma cells with high levels of MYC.
      Overexpression of Pim1 in the mouse prostate induces several pro-tumorigenic
      genetic programs including cell cycle genes and Myc-regulated genes before the
      induction of any discernible pathology. Pim1 depletion by RNA interference in
      mouse and human prostate cancer cells decreased cellular proliferation, survival,
      Erk signaling and tumorigenicity even when MYC levels were not significantly
      altered. These results indicate that PIM1 may be necessary to maintain
      tumorigenicity, and further support efforts aimed at developing PIM1 inhibitors
      for prostate cancer therapy.

PMID- 21860424
TI  - Erythropoietin receptor contributes to melanoma cell survival in vivo.
AB  - Erythropoietin (Epo) is widely used clinically to treat anemia associated with
      various clinical conditions including cancer. Data from several clinical trials
      suggest significant adverse effect of Epo treatment on cancer patient survival.
      However, controversy exists whether Epo receptor (EpoR) is functional in cancer
      cells. In this study, we demonstrated that EpoR mRNA expression was detectable in
      90.1% of 65 melanoma cell lines, and increased copy number of the Epo and EpoR
      loci occurred in 30 and 24.6% of 130 primary melanomas, respectively. EpoR
      knockdown in melanoma cells resulted in diminished ERK phosphorylation in
      response to Epo stimulation, decreased cell proliferation and increased response
      to the inhibitory effect of hypoxia and cisplatin in vitro. EpoR knockdown
      significantly decreased melanoma xenograft size and tumor invasion in vivo. On
      the contrary, constitutive activation of EpoR activated cell proliferation
      pathways in melanoma cells and resulted in increased cell proliferation and
      resistance to hypoxia and cisplatin treatment in vitro. EpoR activation resulted
      in significantly larger xenografts with increased tumor invasion of surrounding
      tissue in vivo. Daily administration of recombinant Epo fails to stimulate
      melanoma growth in vivo, but the treatment increased vascular size in the
      xenografts. Increased local recurrence after excision of the primary tumors was
      observed after Epo treatment. Epo induced angiogenesis in Matrigel plug assays,
      and neutralization of Epo secreted by melanoma cells results in decreased
      angiogenesis. These data support that EpoR is functional in melanoma and EpoR
      activation may promote melanoma progression, and suggest that Epo may stimulate
      angiogenesis and increase survival of melanoma cells under hypoxic condition in
      vivo.

PMID- 21860426
TI  - MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced
      tumor progression.
AB  - The tyrosine kinase c-Src is upregulated in various human cancers; however, the
      molecular mechanisms underlying c-Src-mediated tumor progression remain unclear.
      Here we show that downregulation of microRNA (miR)-542-3p is tightly associated
      with tumor progression via c-Src-related oncogenic pathways. In c-Src-transformed
      fibroblasts and human cancer cells that overexpress c-Src, miR-542-3p is
      substantially downregulated, and the ectopic expression of miR-542-3p suppresses
      tumor growth. We identified the integrin-linked kinase (ILK) as a conserved
      target of miR-542-3p. ILK upregulation promotes cell adhesion and invasion by
      activating the integrin-focal adhesion kinase (FAK)/c-Src pathway, and can also
      contribute to tumor growth via the AKT and glycogen synthase kinase 3beta
      pathways. MiR-542-3p expression is downregulated by the activation of c-Src
      related signaling molecules, including epidermal growth factor receptor, K-Ras
      and Ras/Raf/mitogen-activated protein kinase/extracellular signal-regulated
      kinase. In human colon cancer tissues, downregulation of miR-542-3p is
      significantly correlated with the upregulation of c-Src and ILK. Our results
      suggest that the novel c-Src-miR-542-3p-ILK-FAK circuit plays a crucial role in
      controlling tumor progression.

PMID- 21860425
TI  - Either Kras activation or Pten loss similarly enhance the dominant-stable CTNNB1
      induced genetic program to promote granulosa cell tumor development in the ovary
      and testis.
AB  - WNT, RAS or phosphoinositide 3-kinase signaling pathways control specific stages
      of ovarian follicular development. To analyze the functional interactions of
      these pathways in granulosa cells during follicular development in vivo, we
      generated specific mutant mouse models. Stable activation of the WNT signaling
      effector beta-catenin (CTNNB1) in granulosa cells results in the formation of
      premalignant lesions that develop into granulosa cell tumors (GCTs) spontaneously
      later in life or following targeted deletion of the tumor suppressor gene Pten.
      Conversely, expression of oncogenic KRAS(G12D) dramatically arrests
      proliferation, differentiation and apoptosis in granulosa cells, and
      consequently, small abnormal follicle-like structures devoid of oocytes
      accumulate in the ovary. Because of the potent anti-proliferative effects of
      KRAS(G12D) in granulosa cells, we sought to determine whether KRAS(G12D) would
      block precancerous lesion and tumor formation in follicles of the CTNNB1-mutant
      mice. Unexpectedly, transgenic Ctnnb1;Kras-mutant mice exhibited increased GC
      proliferation, decreased apoptosis and impaired differentiation and developed
      early-onset GCTs leading to premature death in a manner similar to the
      Ctnnb1;Pten-mutant mice. Microarray and reverse transcription-PCR analyses
      revealed that gene regulatory processes induced by CTNNB1 were mostly enhanced by
      either KRAS activation or Pten loss in remarkably similar patterns and degree.
      The concomitant activation of CTNNB1 and KRAS in Sertoli cells also caused
      testicular granulosa cell tumors that showed gene expression patterns that
      partially overlapped those observed in GCTs of the ovary. Although the mutations
      analyzed herein have not yet been linked to adult GCTs in humans, they may be
      related to juvenile GCTs or to tumors in other tissues where CTNNB1 is mutated.
      Importantly, the results provide strong evidence that CTNNB1 is the driver in
      these contexts and that KRAS(G12D) and Pten loss promote the program set in
      motion by the CTNNB1.

PMID- 21860427
TI  - Incidence of extramedullary relapse after haploidentical SCT for advanced
      AML/myelodysplastic syndrome.
AB  - Extramedullary (EM) relapse of leukemia after allo-SCT in patients with
      AML/myelodysplastic syndrome has been increasingly reported. The reduced
      effectiveness of the GVL effect in EM sites, as compared with BM, has been
      suggested to underlie this problem. We retrospectively analyzed the pattern of
      relapse after haploidentical SCT (haplo-SCT), performed as the first or second
      SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative
      incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively.
      Among 19 patients who received haplo-SCT as their second SCT, the cumulative
      incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most
      of the patients who underwent repeat haplo-SCT for the treatment of EM relapse
      had further EM relapse at other sites. Post-relapse survival did not differ
      significantly with different patterns of relapse. The frequent occurrence of EM
      relapse after haplo-SCT, particularly when performed as a second SCT, suggests
      that the potent GVL effect elicited by an HLA disparity also occurs
      preferentially in BM. Our findings emphasize the need for a treatment strategy
      for EM relapse that recognizes the reduced susceptibility of EM relapse to the
      GVL effect.

PMID- 21860428
TI  - Access to allogeneic hematopoietic SCT for patients with MDS or relapsed AML
      treated according to protocols of the Dutch Childhood Oncology Group.
AB  - To investigate whether all patients in need of an allogeneic hematopoietic SCT
      (HSCT) are offered one, we retrospectively investigated the policy for all
      children diagnosed with myelodysplastic syndrome (n=90) or relapsed AML (n=75)
      between 1998 and 2008. These children are registered at diagnosis and treated
      according to protocols of the Dutch Childhood Oncology Group, which provides
      accurate disease incidence data and protocol-indicated appropriateness for HSCT.
      For 48 (30%) patients, a family donor was identified; for 90 (57%) patients, an
      unrelated donor (UD) search was performed; and for 21 (13%) patients, no UD
      search was initiated. Reasons for not initiating an UD search include:
      progressive disease (n=10), conserve quality of life (n=1), stable disease (n=3),
      immunosuppressive therapy (n=2), patient death (n=3), patient lives abroad (n=1)
      and second relapse (n=1). On the basis of the time interval between date of
      diagnosis and date of death/last follow-up, for eight (5%) patients, it may be
      questioned why an UD search was not performed. The fact that 95% of all children
      are given the option of an allogeneic HSCT is encouraging and reasons not to
      transplant seem fair in most cases.

PMID- 21860429
TI  - Reduced-intensity allografting in patients with therapy-related myeloid neoplasms
      and active primary malignancies.
AB  - Therapy-related myeloid neoplasms (t-MNs) are severe long-term consequences of
      cytotoxic treatments for a primary, often, malignant disorder. So far, the
      majority of patients eligible for transplantation have undergone myeloablative
      allo haematopoietic SCT (HSCT) as a potentially curative treatment, but it has
      been associated with high transplantation-related mortality (TRM) rates. In this
      retrospective study, we analysed the outcome of patients with t-MNs undergoing
      HSCT with reduced-intensity conditioning (RIC). Of 55 patients, seen at a single
      centre over a 10-year period, 17 underwent RIC HSCT with related or unrelated
      donors. The estimated overall survival was 53% at 1 year and 47% at 3 years, and
      disease-free survival was 47% at 1 year. At 1 year, the cumulative incidence of
      relapse and TRM were 24% and 30%, respectively. Of five patients with active
      primary neoplasms who underwent transplantation, two are alive beyond 1 year and
      show CR of both t-MNs and the primary malignancy. These data indicate that RIC
      HSCT is an encouraging approach for patients with t-MNs. The issue of primary
      malignancies not being in remission at the time of transplantation should be
      explored in further studies.

PMID- 21860430
TI  - Comparison of childhood leukemia initiating cell populations in NOD/SCID and NSG
      mice.

PMID- 21860431
TI  - Human allo-reactive CD4+ T cells as strong mediators of anti-tumor immunity in
      NOD/scid mice engrafted with human acute lymphoblastic leukemia.
AB  - Adoptive immunotherapy with donor lymphocyte infusion (DLI) after allogeneic stem
      cell transplantation (alloSCT) may not only mediate Graft-versus-Leukemia (GvL)
      reactivity, but also induce Graft-versus-Host Disease (GvHD). As HLA-class II
      molecules are predominantly expressed on hematopoietic cells, CD4+ T cells may
      selectively mediate GvL reactivity without GvHD. Here, we assessed the capacity
      of human CD4+ T cells to act as sole mediators of GvL reactivity in a NOD/scid
      mouse model for human acute lymphoblastic leukemia and chronic myeloid leukemia
      in lymphoid blast crisis. Highly purified CD4+ DLI eradicated the leukemic cells.
      The anti-tumor immunity was mediated by a polyclonal CD4+ T cell response
      comprising cytokine-producing T-helper and cytolytic T-effector cells directed
      against the mismatched HLA-class II molecules of the patients. Furthermore,
      primary leukemic cells acquired an antigen-presenting cell (APC) phenotype in
      vivo after DLI, as well as in vitro after co-culture with leukemia-specific CD4+
      T cells. In conclusion, our results show that CD4+ T cells can be strong
      mediators of anti-tumor immunity, and provide evidence that cross-talk between
      CD4+ T cells and leukemic cells is the basis for induction of leukemic cells with
      an APC phenotype. These data emphasize the clinical relevance of CD4+ T cell
      based immunotherapy as treatment modality for hematological malignancies after
      alloSCT.

PMID- 21860432
TI  - The JAK2V617F oncogene requires expression of inducible
      phosphofructokinase/fructose-bisphosphatase 3 for cell growth and increased
      metabolic activity.
AB  - Myeloproliferative neoplasms are characterized by overproduction of myeloid
      lineage cells with frequent acquisition of oncogenic JAK2V617F kinase mutations.
      The molecular mechanisms that regulate energy requirements in these diseases are
      poorly understood. Transformed cells tend to rely on fermentation instead of more
      efficient oxidative phosphorylation for energy production. Our data in JAK2V617F
      transformed cells show that growth and metabolic activity were strictly dependent
      on the presence of glucose. Uptake of glucose and cell surface expression of the
      glucose transporter Glut1 required the oncogenic tyrosine kinase. Importantly,
      JAK2V617F as well as active STAT5 increased the expression of the inducible rate
      limiting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3),
      which controls glycolytic flux through 6-phosphofructo-1-kinase. PFKFB3 was
      required for JAK2V617F-dependent lactate production, oxidative metabolic activity
      and glucose uptake. Targeted knockdown of PFKFB3 also limited cell growth under
      normoxic and hypoxic conditions and blocked in vivo tumor formation in mice.
      Overall, these data suggest that inducible PFKFB3 is required for increased
      growth, metabolic activity and is regulated through active JAK2 and STAT5. Novel
      therapies that specifically block PFKFB3 activity or expression would, therefore,
      be expected to inhibit JAK2/STAT5-dependent malignancies and related cancers.

PMID- 21860434
TI  - Keeping up with the journals.

PMID- 21860433
TI  - TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti
      leukemic properties.
AB  - TG02 is a novel pyrimidine-based multi-kinase inhibitor that inhibits CDKs 1, 2,
      7 and 9 together with JAK2 and FLT3. It dose-dependently inhibits signaling
      pathways downstream of CDKs, JAK2 and FLT3 in cancer cells with the main targets
      being CDKs. TG02 is anti-proliferative in a broad range of tumor cell lines,
      inducing G1 cell cycle arrest and apoptosis. Primary cultures of progenitor cells
      derived from acute myeloid leukemia (AML) and polycythemia vera patients are very
      sensitive to TG02. Comparison with reference inhibitors that block only one of
      the main targets of TG02 demonstrate the benefit of combined CDK and JAK2/FLT3
      inhibition in cell lines as well as primary cells. In vivo, TG02 exhibits
      favorable pharmacokinetics after oral dosing in xenograft models and accumulates
      in tumor tissues, inducing an effective blockade of both CDK and STAT signaling.
      TG02 induces tumor regression after oral dosing on both daily and intermittent
      schedules in a murine model of mutant-FLT3 leukemia (MV4-11) and prolongs
      survival in a disseminated AML model with wild-type FLT3 and JAK2 (HL-60). These
      data demonstrate that TG02 is active in various models of leukemia and provide a
      rationale for the ongoing clinical evaluation of TG02 in patients with advanced
      leukemias.

PMID- 21860435
TI  - Spellbound by books.

PMID- 21860443
TI  - Nanoscale electrochemistry: feeling the strain.
AB  - Characterizing electrochemical behaviour on the nanometre scale is fundamental to
      gaining complete insight into the working mechanisms of fuel cells. The
      application of a new scanning probe microscopy technique can now relate local
      surface structure to electrochemical activity at a resolution below 10 nm.

PMID- 21860444
TI  - Molecularly imprinted polymers: smart hydrogel crystal gardens.
AB  - Growing good-quality single crystals of proteins for high-resolution X-ray
      diffraction relies on the use of a diverse range of materials as nucleating
      agents. Smart hydrogels, in the form of molecularly imprinted polymers, may
      provide a general solution.

PMID- 21860445
TI  - Analytical chemistry: sweet solution to sensing.
AB  - Glucose meters allow rapid and quantitative measurement of blood sugar levels for
      diabetes sufferers worldwide. Now a new method allows this proven technology to
      be used to quantify a much wider range of analytes.

PMID- 21860446
TI  - Burgenstock 2011: a stereochemical sojourn.
AB  - Stereochemistry represents a common thread uniting chemists from a range of sub
      disciplines at the Burgenstock conference, an annual scientific meeting rich in
      tradition and characterized by intensive, interdisciplinary discussion.

PMID- 21860447
TI  - Ion-protein coordination: the many faces of a proton.
AB  - A joint X-ray/neutron diffraction study has enabled the direct observation of a
      hydronium ion coordinated by three amino-acid residues of an enzyme. This
      sighting will affect our views on how enzymes transport and use protons.

PMID- 21860448
TI  - Two-dimensional chirality: intelligent design.
AB  - Achiral molecules have now been assembled into a homochiral porous network at a
      solid-liquid interface. This has implications for practical processes such as
      separations, but also for understanding how homochirality - crucial in biological
      systems - arose from achiral or racemic species.

PMID- 21860450
TI  - Chemistry beyond the bench.

PMID- 21860451
TI  - Sex and the citadel of science.
AB  - One hundred years on from Marie Curie being awarded her second Nobel Prize there
      has been only a handful of female scientists who have received the call from
      Stockholm. Why are women still under-represented? A lack of ability or passion,
      or could it be that we create labs into which women don't quite fit?

PMID- 21860449
TI  - Protein dynamics: whispering within.
AB  - Dynamic communication between atoms within folded proteins is potentially
      important for function, but its measurement has been a challenge. Now, a combined
      NMR and modelling study provides insights on the presence and strengths of such
      correlations.

PMID- 21860452
TI  - Communicating chemistry for public engagement.
AB  - The communication of chemistry to wider society is difficult because of
      'chemophobia', its inherent complexity and its lack of unifying grand themes. To
      engage with citizens about the benefits and related dangers of the field,
      chemists must improve their dialogue with broader sections of the public - but
      how?

PMID- 21860453
TI  - The two faces of chemistry in the developing world.
AB  - Chemistry creates both agony and hope in less-developed countries - although it
      may provide solutions to many of the problems faced there, the lack of expertise
      and poor infrastructure renders research extremely difficult. What challenges
      must scientists overcome and what can be done to improve matters?

PMID- 21860454
TI  - From crazy chemists to engaged learners through education.
AB  - As well as teaching students what we know, it is becoming increasingly important
      to teach them how we think. We must take a scientific approach to science
      education and experiment with teaching methods, including context-led work and
      media-rich resources, to foster active and independent student engagement.

PMID- 21860455
TI  - The changing landscape of careers in the chemical industry.
AB  - Changes in the chemical industry over the past decade - ranging from
      globalization to an increased focus on speciality chemicals - threaten to leave
      the aspiring industrial chemist unprepared. This Commentary discusses those
      changes and outlines strategies to enter the job market as well equipped as
      possible.

PMID- 21860456
TI  - Minerals go critical.
AB  - The spectre of insecure supplies of some mineral raw materials could hinder the
      development and deployment of new technology. This Commentary discusses and
      analyses the reasons behind the potential insecurity, how markets are responding,
      and what roles government should play.

PMID- 21860457
TI  - Getting physical to fix pharma.
AB  - Powerful technologies allow the synthesis and testing of large numbers of new
      compounds, but the failure rate of pharmaceutical R&D remains very high. Greater
      understanding of the fundamental physical chemical behaviour of molecules could
      be the key to greatly enhancing the success rate of drug discovery.

PMID- 21860459
TI  - A route to enantiopure RNA precursors from nearly racemic starting materials.
AB  - The single-handedness of biological molecules is critical for molecular
      recognition and replication processes and would seem to be a prerequisite for the
      origin of life. A drawback of recently reported synthetic routes to RNA is the
      requirement for enantioenriched reactants, which fails to address the puzzle of
      how the single chirality of biological molecules arose. Here, we report the
      synthesis of highly enantioenriched RNA precursor molecules from racemic starting
      materials, with the molecular asymmetry derived solely from a small initial
      imbalance of the amino-acid enantiomers present in the reaction mixture. Acting
      as spectators to the main reaction chemistry, the amino acids orchestrate a
      sequence of physical and chemical amplification processes. The emergence of
      molecules of single chirality from complex, multi-component mixtures supports the
      robustness of this synthesis process under potential prebiotic conditions and
      provides a plausible explanation for the single-handedness of biological
      molecules before the emergence of self-replicating informational polymers.

PMID- 21860458
TI  - Using personal glucose meters and functional DNA sensors to quantify a variety of
      analytical targets.
AB  - Portable, low-cost and quantitative detection of a broad range of targets at home
      and in the field has the potential to revolutionize medical diagnostics and
      environmental monitoring. Despite many years of research, very few such devices
      are commercially available. Taking advantage of the wide availability and low
      cost of the pocket-sized personal glucose meter-used worldwide by diabetes
      sufferers-we demonstrate a method to use such meters to quantify non-glucose
      targets, ranging from a recreational drug (cocaine, 3.4 uM detection limit) to an
      important biological cofactor (adenosine, 18 uM detection limit), to a disease
      marker (interferon-gamma of tuberculosis, 2.6 nM detection limit) and a toxic
      metal ion (uranium, 9.1 nM detection limit). The method is based on the target
      induced release of invertase from a functional-DNA-invertase conjugate. The
      released invertase converts sucrose into glucose, which is detectable using the
      meter. The approach should be easily applicable to the detection of many other
      targets through the use of suitable functional-DNA partners (aptamers, DNAzymes
      or aptazymes).

PMID- 21860460
TI  - Measuring oxygen reduction/evolution reactions on the nanoscale.
AB  - The efficiency of fuel cells and metal-air batteries is significantly limited by
      the activation of oxygen reduction and evolution reactions. Despite the well
      recognized role of oxygen reaction kinetics on the viability of energy
      technologies, the governing mechanisms remain elusive and until now have been
      addressable only by macroscopic studies. This lack of nanoscale understanding
      precludes optimization of material architecture. Here, we report direct
      measurements of oxygen reduction/evolution reactions and oxygen vacancy diffusion
      on oxygen-ion conductive solid surfaces with sub-10 nm resolution. In
      electrochemical strain microscopy, the biased scanning probe microscopy tip acts
      as a moving, electrocatalytically active probe exploring local electrochemical
      activity. The probe concentrates an electric field in a nanometre-scale volume of
      material, and bias-induced, picometre-level surface displacements provide
      information on local electrochemical processes. Systematic mapping of oxygen
      activity on bare and platinum-functionalized yttria-stabilized zirconia surfaces
      is demonstrated. This approach allows direct visualization of the oxygen
      reduction/evolution reaction activation process at the triple-phase boundary, and
      can be extended to a broad spectrum of oxygen-conductive and electrocatalytic
      materials.

PMID- 21860461
TI  - Control and induction of surface-confined homochiral porous molecular networks.
AB  - Homochirality is essential to many biological systems, and plays a pivotal role
      in various technological applications. The generation of homochirality and an
      understanding of its mechanism from the single-molecule to supramolecular level
      have received much attention. Two-dimensional chirality is a subject of intense
      interest due to the unique possibilities and consequences of confining molecular
      self-assembly to surfaces or interfaces. Here, we report the perfect generation
      of two-dimensional homochirality of porous molecular networks at the liquid-solid
      interface in two different ways: (i) by self-assembly of homochiral building
      blocks and (ii) by self-assembly of achiral building blocks in the presence of a
      chiral modifier via a hierarchical structural recognition process, as revealed by
      scanning tunnelling microscopy. The present results provide important impetus for
      the development of two-dimensional crystal engineering and may afford
      opportunities for the utilization of chiral nanowells in chiral recognition
      processes, as nanoreactors and as data storage systems.

PMID- 21860462
TI  - Peptide-nucleotide microdroplets as a step towards a membrane-free protocell
      model.
AB  - Although phospholipid bilayers are ubiquitous in modern cells, their
      impermeability, lack of dynamic properties, and synthetic complexity are
      difficult to reconcile with plausible pathways of proto-metabolism, growth and
      division. Here, we present an alternative membrane-free model, which demonstrates
      that low-molecular-weight mononucleotides and simple cationic peptides
      spontaneously accumulate in water into microdroplets that are stable to changes
      in temperature and salt concentration, undergo pH-induced cycles of growth and
      decay, and promote alpha-helical peptide secondary structure. Moreover, the
      microdroplets selectively sequester porphyrins, inorganic nanoparticles and
      enzymes to generate supramolecular stacked arrays of light-harvesting molecules,
      nanoparticle-mediated oxidase activity, and enhanced rates of glucose
      phosphorylation, respectively. Taken together, our results suggest that peptide
      nucleotide microdroplets can be considered as a new type of protocell model that
      could be used to develop novel bioreactors, primitive artificial cells and
      plausible pathways to prebiotic organization before the emergence of lipid-based
      compartmentalization on the early Earth.

PMID- 21860463
TI  - The transcription factor FOXM1 is a cellular target of the natural product
      thiostrepton.
AB  - Transcription factors are proteins that bind specifically to defined DNA
      sequences to promote gene expression. Targeting transcription factors with small
      molecules to modulate the expression of certain genes has been notoriously
      difficult to achieve. The natural product thiostrepton is known to reduce the
      transcriptional activity of FOXM1, a transcription factor involved in
      tumorigenesis and cancer progression. Herein we demonstrate that thiostrepton
      interacts directly with FOXM1 protein in the human breast cancer cells MCF-7.
      Biophysical analyses of the thiostrepton-FOXM1 interaction provide additional
      insights on the molecular mode of action of thiostrepton. In cellular
      experiments, we show that thiostrepton can inhibit the binding of FOXM1 to
      genomic target sites. These findings illustrate the potential druggability of
      transcription factors and provide a molecular basis for targeting the FOXM1
      family with small molecules.

PMID- 21860464
TI  - Reactions of the inner surface of carbon nanotubes and nanoprotrusion processes
      imaged at the atomic scale.
AB  - Although the outer surface of single-walled carbon nanotubes (atomically thin
      cylinders of carbon) can be involved in a wide range of chemical reactions, it is
      generally thought that the interior surface of nanotubes is unreactive. In this
      study, we show that in the presence of catalytically active atoms of rhenium
      inserted into nanotubes, the nanotube sidewall can be engaged in chemical
      reactions from the inside. Aberration-corrected high-resolution transmission
      electron microscopy operated at 80 keV allows visualization of the formation of
      nanometre-sized hollow protrusions on the nanotube sidewall at the atomic level
      in real time at ambient temperature. Our direct observations and theoretical
      modelling demonstrate that the nanoprotrusions are formed in three stages: (i)
      metal-assisted deformation and rupture of the nanotube sidewall, (ii) the fast
      formation of a metastable asymmetric nanoprotrusion with an open edge and (iii) a
      slow symmetrization process that leads to a stable closed nanoprotrusion.

PMID- 21860466
TI  - All about arsenic.
AB  - If ever there was an element that epitomizes the notion that chemicals might be
      good or bad depending on their use, arsenic must be it. Katherine Haxton explains
      why.

PMID- 21860465
TI  - Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids
      controlled by laboratory evolution.
AB  - A current challenge in synthetic organic chemistry is the development of methods
      that allow the regio- and stereoselective oxidative C-H activation of natural or
      synthetic compounds with formation of the corresponding alcohols. Cytochrome P450
      enzymes enable C-H activation at non-activated positions, but the simultaneous
      control of both regio- and stereoselectivity is problematic. Here, we demonstrate
      that directed evolution using iterative saturation mutagenesis provides a means
      to solve synthetic problems of this kind. Using P450 BM3(F87A) as the starting
      enzyme and testosterone as the substrate, which results in a 1:1 mixture of the
      2beta- and 15beta-alcohols, mutants were obtained that are 96-97% selective for
      either of the two regioisomers, each with complete diastereoselectivity. The
      mutants can be used for selective oxidative hydroxylation of other steroids
      without performing additional mutagenesis experiments. Molecular dynamics
      simulations and docking experiments shed light on the origin of regio- and
      stereoselectivity.

PMID- 21860467
TI  - Evaluation of the Value of Combined Urine Cytology and Cystoscopy for Follow-up
      of Superficial Transitional Cell Carcinoma of the Urinary Bladder.
AB  - OBJECTIVE: Cystoscopic biopsy is the most accurate technique used to assess the
      efficacy of treatment and to detect recurrence of superficial TCC of urinary
      bladder. Implementation of voided urine cytology to detect tumor cells in urine
      samples may represent an additional tool. The aims of this study are: (1) To
      estimate the reliability of combined cystoscopy and urine cytology examination in
      the follow-up of cases of superficial urinary bladder carcinoma, which might help
      to restrict cystoscopic biopsies for these cases with its morbidity and cost, (2)
      To discuss the diagnostic pitfalls of cytologic examination in these cases.
      PATIENTS AND METHODS: This is a prospective study, on 93 patients with
      superficial TCC of urinary bladder who were initially treated by complete TUR
      with or without adjuvant intravesical therapy with Bacillus Calmette - Guerin
      (BCG) (120mg/instillation) every week for 6 weeks. Cystoscopic findings, urine
      cytology and histologic results of cystoscopic biopsies were assessed. RESULTS:
      By histologic examination, 41 (44%) cases were recurrent TCC and 52 (56%) were
      reported as negative for recurrence. By cystoscopic examination there were 36
      positive cases, 4 of them were false positive. Out of the 57 negative cases for
      recurrence cystoscopically, 9 were histologically positive and were considered as
      false negative results. By cytology, 28 cases were positive, 3 were false
      positive, and 65 were negative for recurrence, 16 of them were false negative.
      Most of false negative cases were low grade TCC. Sensitivity of cytology and
      cystoscopy in the detection of recurrence was 61% and 78% respectively. When the
      two examinations were combined, sensitivity was 100%, and specificity was 92.3%.
      CONCLUSION: For follow-up of superficial bladder carcinoma, the combination of
      negative cystoscopic findings and negative urine cytology may replace routine
      biopsies with their morbidity and cost. KEY WORDS: Superficial bladder carcinoma 
      Cytology and Cystoscopy - Follow-up.

PMID- 21860468
TI  - Outcome and prognostic factors of uterine sarcoma in 59 patients: single
      institutional results.
AB  - PURPOSE: Uterine corpus sarcomas are rare heterogeneous tumors characterized by
      rapid progression and poor response to treatment. This series investigated
      treatment options, relapse pattern, survival and prognostic factors. PATIENTS AND
      METHODS: A total of 59 patients were treated in the National Cancer Institute,
      Cairo University, (2000-2007). Leiomyosarcoma accounted for 42.2% followed by
      carcinosarcoma (35.5%) and endometrial stromal sarcoma (18.6%). 40.7% had FIGO
      stage I disease, 30.5% were II, 16.9% were III and 11.9% were IV. Surgery was the
      primary line of treatment for all cases with total abdominal hysterectomy and
      bilateral salpingoophorectomy in 88% of cases and 12% had less extensive surgery.
      Twenty-four (40.7%) patients had surgery alone, 24 (40.7%) had surgery and
      radiotherapy, 7 (11.9%) had surgery and chemo-irradiation and 4 (6.7%) had
      surgery and chemotherapy. RESULTS: After 27.4 months mean follow-up (range: 2
      69), relapses were detected in 32 patients (59.2%) including 19 (59%) systemic
      metastases. Stage, adjuvant irradiation, tumor size, myometrial invasion,
      vascular and cervix invasion were significant factors in univariate analysis;
      nevertheless, multivariate prognostic factors were only stage (p=0.04) and
      adjuvant irradiation (p=0.01). 5-year cumulative disease free survival for stage
      I was 63.6%, 41.2% for stage II, 10% for stage III and 0% in stage IV. Neither
      extent of surgery, chemotherapy, histologic type or grade had significant effect
      on survival. Adjuvant radiotherapy offered 62% 2-year cumulative overall survival
      versus 22% for surgery alone and surgery with chemotherapy. Salvage surgery for
      isolated relapses was performed for 9/32 recurrent patients (28%) including 5
      lung metastatectomies and 4 local pelvic resections. Mean survival after
      pulmonary resections was 7.4 months (6-14). CONCLUSION: Diagnosis of uterine
      sarcoma is in itself a poor prognostic factor. Complete cytoreductive surgery and
      adjuvant radiotherapy is essential for local control, provided tumor is limited
      to the uterus. Adjuvant irradiation showed survival benefit. KEY WORDS: Uterine
      cancer - Uterine sarcoma - Uterine sarcoma treatment - Sarcoma irradiation -
      Sarcoma prognosis.

PMID- 21860469
TI  - The Role of P63 Immunocytochemistry for Myoepithelial Cells in the Diagnosis of
      Atypical and Suspicious Cases in Breast Fine Needle Aspiration Cytology (FNAC).
AB  - PURPOSE: Evaluation of the usefulness of p63 immunocytochemical marker for
      myoepithelial cells in the diagnosis of atypical and suspicious lesions in breast
      cytology. PATIENTS AND METHODS: This is a retrospective study on 122 selected
      patients presented at Cytology Unit, Pathology Department, NCI, Cairo University,
      in three years interval from 2007 to 2009, with breast lumps who underwent
      preoperative FNAC and diagnosed cytologically as atypical or suspicious breast
      lesion for biopsy then they were followed by excisional biopsy for
      histopathologic assessment that was considered as the golden standard diagnosis
      against which FNAC diagnoses were compared. Paucicellular cytologic slides as
      well as cases with no corresponding final histopathological diagnosis were
      excluded. The destained cytologic slides were subjected to p63 immunocytochemical
      staining. Only the nuclear immunoreactivity for p63 was considered specific,
      cytoplasmic and membranous staining was considered nonspecific. The stained
      slides with p63 marker were quantified according to the percentages of positive
      epithelial cell clusters and positive single bare nuclei in the BACKGROUND. The
      immunocytochemical results were compared with histopathologic diagnoses. RESULTS:
      Of the 122 studied breast aspirates, 84 cases with atypical findings and 38 cases
      with suspicious findings were included. The two categories yielded malignant
      diagnoses in 53 cases (63.1%) and 31 cases (81.6%), respectively. Invasive duct
      carcinoma was the most common malignant diagnosis in both categories. The most
      common benign diagnosis in the atypical group was fibrocystic changes (48.4%),
      while atypical ductal hyperplasia was the most common non-malignant diagnosis in
      the suspicious group (42.8%). P63 consistently stained the nuclei of
      myoepithelial cells, either overlying clusters and/or single bare nuclei. Of the
      histologically confirmed malignant cases 69% and 91.7% showed no p63 nuclear
      staining in cell clusters or bare nuclei, respectively; while cases showed
      staining pattern similar to that of benign lesions. On the other hand, 84.2% and
      57.9% of the benign cases showed staining in more than 75% of the clusters and
      bare nuclei, respectively. The staining pattern of p63 was significantly
      different between malignant and benign lesions (p-value <0.005). The p63
      sensitivity, specificity, positive, and negative predictive value were 90.5%,
      84.2%, 92.7%, and 80%, respectively. Scattered p63 positive ductal cells ( <10%
      of duct cells) were detected in 6% of all malignant cases. CONCLUSION: The p63
      was a reliable nuclear marker of myoepithelial cells in breast cytology. Benign
      and malignant breast lesions showed significantly different staining pattern for
      p63 on inconclusive breast cytology. The diagnostic sensitivity, specificity,
      positive and negative predictive value of p63 marker were 90.5%, 84.2%, 92.7%,
      and 80% respectively. The p63 immunostaining may be used as a diagnostic adjunct
      to the routine fine needle aspiration cytology in cases of breast lesions with
      atypical and suspicious results. KEY WORDS: P63 immunocytochemistry - Breast FNAC
      - Inconclusive diagnoses.

PMID- 21860470
TI  - Role of Sonoelastography in the Differentiation between Benign and Malignant
      Breast Lesions.
AB  - PURPOSE: To prospectively evaluate the accuracy of real time elastography
      (ultrasound strain imaging) for distinguishing between benign and malignant solid
      breast lesions with the pathologic results as the reference standard. We also
      evaluated if the fat/lesion ratio could semiquantitatively evaluate the stiffness
      of breast lesions. PATIENTS AND METHODS: Conventional ultrasonography (US) and
      real time elastography were performed in 100 women with breast masses with the
      mean age is 50 years. Elasticity images were given an elasticity score according
      to the degree and distribution of the strain induced by light compression with 1
      3 is benign and 4-5 is malignant. We also calculated the ratio of the normal
      breast tissue to that of the lesion (fat/lesion ratio) of the different breast
      lesions with the fat as the reference. The cutoff point was 4.8 with ratio below
      this level is considered benign and above this level is considered malignant.
      RESULTS: For elasticity score, the mean standard deviation was 4.1 for malignant
      lesions and 2.1 for benign lesions (p<0.001). When a cutoff point between 3 and 4
      was used, elastography had 87.2% sensitivity, 90.6% specificity and 90% accuracy.
      The fat/lesion ratio (F/L ratio) of the benign lesions was different from that of
      the malignant ones. CONCLUSION: US strain imaging can facilitate improved
      classification of benign and malignant breast masses and has the potential to aid
      their diagnosis. By using the F/L ratio, the stiffness of breast lesions could be
      semiquantitated and this method may provide another diagnostic method in addition
      to the scoring system. KEY WORDS: Breast - Sonoelastography - Strain imaging -
      Fat-lesion ratio.

PMID- 21860471
TI  - Esthesioneuroblastoma: the role of post-operative irradiation after complete
      surgical resection.
AB  - BACKGROUND: Esthesioneuroblastoma is a rare tumor and this retrospective report
      was done to evaluate the role of post-operative radiotherapy after complete
      surgical resection of the tumor. PATIENTS AND METHODS: Twenty nine patients with
      Esthesioneuroblastoma of Kadish stages A (1), B (19), C (6) and unknown (3) were
      retrospectively identified through the hospital data-base, patients charts,
      imaging studies and computerized notes between 1995 to 2007 at Department of
      Radiation Oncology, University of Michigan, U.S.A. RESULTS: After complete
      surgical resection (mostly craniofacial resection) of the tumor, 13 (44.8%)
      patients received post-operative radiotherapy to the tumor bed and 16 (45.2%)
      patients did not receive. Only one patient received adjuvant nodal irradiation.
      At a median followup 80 months, local recurrence developed in 11 of 16 (68.7%)
      patients in the group which did not receive postoperative radiotherapy, compared
      with 2 of 13 (15.3%) patients in the group which received. Disease free
      cumulative survival rate at 5-years was 88% for the group which received post
      operative radiotherapy compared with 35% for the group which did not receive
      (p=0.02). Lymph node recurrence in retropharyngeal and level II nodes was
      observed in 7 (24%) patients of whole group. CONCLUSION: Adjuvant radiotherapy to
      the tumor bed after craniofacial resection improves significantly local control
      and disease free survival. Our results suggest that in addition to the tumor bed,
      prophylactic irradiation of the upper neck is necessary in patients with Kadish
      stages B and C. KEY WORDS: Esthesioneuroblastoma - Radiotherapy - Surgery.

PMID- 21860472
TI  - 1,1-Dimethylhydrazine.

PMID- 21860474
TI  - Dimethylvinyl chloride.

PMID- 21860473
TI  - Dimethyl sulfate.

PMID- 21860475
TI  - Melphalan.

PMID- 21860476
TI  - Methoxsalen with ultraviolet A therapy.

PMID- 21860477
TI  - 2-Methylaziridine.

PMID- 21860478
TI  - 4,4'-Methylenebis(2-chloroaniline).

PMID- 21860479
TI  - 4,4'-Methylenebis(N,N-dimethyl)benzenamine.

PMID- 21860480
TI  - 4,4'-Methylenedianiline and its dihydrochloride.

PMID- 21860481
TI  - Methyleugenol.

PMID- 21860482
TI  - Methyl methanesulfonate.

PMID- 21860483
TI  - Metronidazole.

PMID- 21860484
TI  - Michler's ketone.

PMID- 21860485
TI  - Mineral oils: untreated and mildly treated.

PMID- 21860486
TI  - Mirex.

PMID- 21860487
TI  - Mustard gas.

PMID- 21860488
TI  - Naphthalene.

PMID- 21860489
TI  - 2-Naphthylamine.

PMID- 21860490
TI  - Nickel compounds and metallic nickel.

PMID- 21860491
TI  - Nitrilotriacetic acid.

PMID- 21860492
TI  - o-Nitroanisole.

PMID- 21860493
TI  - Nitroarenes (selected): 1,6-Dinitropyrene.

PMID- 21860494
TI  - Nitroarenes (selected): 1,8-Dinitropyrene.

PMID- 21860495
TI  - Nitroarenes (selected): 6-Nitrochrysene.

PMID- 21860496
TI  - Nitroarenes (selected): 1-Nitropyrene.

PMID- 21860497
TI  - Nitroarenes (selected): 4-Nitropyrene.

PMID- 21860499
TI  - Nitrofen.

PMID- 21860498
TI  - Nitrobenzene.

PMID- 21860500
TI  - Nitrogen mustard hydrochloride.

PMID- 21860501
TI  - Nitromethane.

PMID- 21860502
TI  - 2-Nitropropane.

PMID- 21860503
TI  - N-Nitrosamines (15 listings): N-Methyl-N'-Nitro-N-Nitrosoguanidine.

PMID- 21860504
TI  - N-Nitrosamines (15 listings): N-Nitrosodi-n-butylamine.

PMID- 21860505
TI  - N-Nitrosamines (15 listings): N-Nitrosodiethanolamine.

PMID- 21860506
TI  - N-Nitrosamines (15 listings): N-Nitrosodiethylamine.

PMID- 21860507
TI  - N-Nitrosamines (15 listings): N-Nitrosodimethylamine.

PMID- 21860508
TI  - N-Nitrosamines (15 listings): N-Nitrosodi-n-propylamine.

PMID- 21860509
TI  - N-Nitrosamines (15 listings): N-Nitroso-N-ethylurea.

PMID- 21860510
TI  - N-Nitrosamines (15 listings): 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone.

PMID- 21860511
TI  - N-Nitrosamines (15 listings): N-Nitroso-N-methylurea.

PMID- 21860512
TI  - N-Nitrosamines (15 listings): N-Nitrosomethylvinylamine.

PMID- 21860513
TI  - N-Nitrosamines (15 listings): N-nitrosomorpholine.

PMID- 21860514
TI  - N-Nitrosamines (15 listings): N-Nitrosonornicotine.

PMID- 21860515
TI  - N-Nitrosamines (15 listings): N-Nitrosopiperidine.

PMID- 21860516
TI  - N-Nitrosamines (15 listings): N-Nitrosopyrrolidine.

PMID- 21860517
TI  - N-Nitrosamines (15 listings): N-Nitrososarcosine.

PMID- 21860518
TI  - Nitrosourea chemotherapeutic agents: Bis(chloroethyl) nitrosourea.

PMID- 21860519
TI  - Nitrosourea chemotherapeutic agents: 1-(2-Chloroethyl)-3-cyclohexyl-1
      nitrosourea.

PMID- 21860520
TI  - Nitrosourea chemotherapeutic agents: 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1
      nitrosourea.

PMID- 21860521
TI  - Nitrosourea chemotherapeutic agents: Chlorozotocin.

PMID- 21860522
TI  - Nitrosourea chemotherapeutic agents: Streptozotocin.

PMID- 21860523
TI  - Norethisterone.

PMID- 21860524
TI  - Ochratoxin A.

PMID- 21860525
TI  - 4,4'-Oxydianiline.

PMID- 21860526
TI  - Oxymetholone.

PMID- 21860527
TI  - Therapeutic approaches to vascular protection in ischemic stroke.
AB  - Reperfusion with recombinant tissue plasminogen activator (tPA) sometimes causes
      catastrophic hemorrhagic transformation (HT) in the ischemic brain. Consequently,
      the application of tPA has been strictly limited. Recent studies have indicated
      that matrix metalloproteinases (MMPs), especially MMP-9, play a critical role in
      blood brain barrier (BBB) disruption in the ischemic brain, leading to brain
      edema and HT. In the ischemic brain, free radicals and exogenous tPA itself can
      trigger MMP-9 activation through several signaling pathways containing LDL
      receptor-related protein (LRP) and proteinase-activated receptor 1 (PAR1).
      Therapeutic targeting of free radicals and MMP-9/t-PA related signaling pathways
      might be promising approaches to minimizing catastrophic HT in acute stroke
      patients. We provide an overview of the available scientific reports to improve
      our understanding of the mechanisms leading to HT, and highlight recent progress
      in the development of new therapeutic strategies for preventing HT in the post
      stroke brain.

PMID- 21860528
TI  - Postmortem changes in myoglobin content in organs.
AB  - Postmortem changes in myoglobin concentrations in blood and organs were
      investigated using an enzyme immunoassay by animal experiments in combination
      with immunohistochemical staining of human cases. Blood myoglobin concentrations
      were found to increase drastically within a very short time after death. Those in
      striated muscle, however, did not change by day 14 postmortem. Myoglobin content
      in the liver and kidney increased slightly by day 5 postmortem, and more
      obviously by day 7 or later. However, almost no change was observed by day 5 in
      the kidney when the renal artery and vein had been ligated just after death. In
      the thyroid gland and the lung, the myoglobin content markedly increased by day 7
      postmortem, with the logarithmical values rising nearly linearly as the time
      after death passed. In the thyroid gland, concentrations reached the level of the
      striated muscle. The mechanisms of postmortem myoglobin increase in organs are
      thought to be direct diffusion from the striated muscle and/or distribution
      through the blood. To estimate the postmortem interval, the determination of
      myoglobin content in the thyroid gland or the lung appears to be useful.

PMID- 21860529
TI  - Clinical efficacy of capecitabine and cyclophosphamide (XC) in patients with
      metastatic breast cancer.
AB  - Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC)
      has been demonstrated to be useful for long-term control of lesions in patients
      with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and
      prolongation of survival. Here, a retrospective review was conducted of MBC
      patients administered XC at the Okayama University Hospital (OUH), to evaluate
      responses to XC, adverse events and time to progression (TTP). Twenty patients
      with MBC received XC between 2006 and 2009. With the exception of 2 elderly
      patients who were over the age of 70 at the initial examination, all of the
      patients had received prior treatment with an anthracycline and/or a taxane. No
      complete response (CR) cases were observed, but partial response (PR) was
      achieved in 6 patients (30%) and SD in 9 (45%), of whom 5 (20%) sustained SD
      status for >12 months. The median TTP was 6 months (range:3-27 mo.). Three
      patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis), but
      no other patients developed adverse reactions causing interruption of the
      therapy. XC was safe even in previously treated and elderly MBC
      patients;moreover, it yielded remarkable clinical responses.

PMID- 21860530
TI  - Carotid endarterectomy for symptomatic complete occlusion of the internal carotid
      artery.
AB  - We described 9 consecutive patients who underwent operative carotid artery
      exploration with attempted carotid endarterectomy (CEA) for symptomatic internal
      carotid artery (ICA) occlusion. Indications for this surgery based on vascular
      imaging included segmental occlusion of the proximal ICA and also extensive
      occlusion of the distal ICA in selected patients in whom color-flow duplex
      ultrasound showed a poorly echogenic or anechoic thrombus with a flow void,
      suggestive of an acute thrombus. CEA was performed successfully to restore blood
      flow in all 9 patients:CEA in 5 and CEA with Fogarty thrombectomy in 4.
      Postoperative magnetic resonance (MR) angiography confirmed that
      revascularization had been successful in all 9 patients, and MR imaging displayed
      improved perfusion in 4 patients. Despite the lack of a generalized efficacy of
      surgical revascularization for symptomatic ICA occlusion, our study demonstrated
      that preoperative vascular imaging allows the selection of patients who may
      benefit from CEA.

PMID- 21860531
TI  - Involvement of MAPKs in ICAM-1 expression in glomerular endothelial cells in
      diabetic nephropathy.
AB  - Inflammatory processes are involved in the pathogenesis of diabetic nephropathy.
      The aim of this study was to clarify the role of mitogen-activated protein kinase
      (MAPK) pathways for induction of intercellular adhesion molecule-1 (ICAM-1)
      expression in glomerular endothelial cells under diabetic conditions. We examined
      the expression of ICAM-1 in the kidneys of experimental diabetic rats. Human
      glomerular endothelial cells (GE cells) were exposed to normal glucose
      concentration, high glucose concentration (HG), or high mannitol concentration
      (HM), and then the expression of the ICAM-1 protein and the phosphorylation of
      the 3 subfamilies of mitogen-activated protein kinase (MAPK) were determined
      using Western blot analysis. Next, to evaluate the involvement of MAPKs in HG- or
      HM-induced ICAM-1 expression, we preincubated GE cells with the inhibitors for
      ERK, p38 or JNK 1h prior to the application of glucose or mannitol. Expression of
      ICAM-1 was increased in the glomeruli of diabetic rats. Both HG and HM induced
      ICAM-1 expression and phosphorylation of ERK1/2, p38 and JNK in GE cells.
      Expression of ICAM-1 was significantly attenuated by inhibitors of ERK, p38 and
      JNK. We conclude that activation of ERK1/2, p38 and JNK cascades may be involved
      in ICAM-1 expression in glomerular endothelial cells under diabetic conditions.

PMID- 21860532
TI  - Is adenosine deaminase in pleural fluid a useful marker for differentiating
      tuberculosis from lung cancer or mesothelioma in Japan, a country with
      intermediate incidence of tuberculosis?
AB  - The objective of this study was to evaluate the utility of the determination of
      adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis
      between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE)
      in Japan, a country with intermediate incidence of tuberculosis (TB). We
      retrospectively reviewed the clinical records of 435 patients with pleural
      effusion and investigated their pleural ADA levels as determined by an auto
      analyzer. ROC analysis was also performed. The study included patients with MPE
      (n=188), TPE (n=124), benign nontuberculous pleural effusion (n=94), and pleural
      effusion of unknown etiology (n=29). The median ADA level in the TPE group was
      70.8U/L, which was significantly higher than that in any other groups (p<0.05).
      The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level
      for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and
      negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As
      many as 9% of patients with lung cancer and 15% of those with mesothelioma were
      false-positive with this ADA cutoff setting. Although the ADA activity in pleural
      fluid can help in the diagnosis of TPE, it should be noted that some cases of
      lung cancer or mesothelioma show high ADA activity in geographical regions with
      intermediate incidence of TB, in contrast to high prevalence areas.

PMID- 21860533
TI  - Preoperative graft volume assessment with 3D-CT volumetry in living-donor lobar
      lung transplantations.
AB  - To determine the effectiveness of living-donor lobar lung transplantation
      (LDLLT), it is necessary to predict the recipient's postoperative lung function.
      Traditionally, Date's formula, also called the segmental ratio, has used the
      number of lung segments to estimate the forced vital capacity (FVC) of grafts in
      LDLLT. To provide a more precise estimate of graft FVC, we calculated the volumes
      of the lower lobe and total lung using three-dimensional computed tomography (3D
      CT) and the volume ratio between them. We calculated the volume ratio in 52
      donors and tested the difference between the segmental volume ratios with a one
      tailed t-test. We also calculated the predicted graft FVC in 21 LDLLTs using the
      segmental ratio pFVC(c) and the volume ratio pFVC(v), and then found the
      Pearson's correlation coefficients for both pFVC(c) and pFVC(v) with the
      recipients' actual FVC (rFVC) measured spirometrically 6 months after surgery.
      Significant differences were found between the segmental ratio and the average
      volume ratio for both sides (right, p=0.03;left, p=0.0003). Both pFVC(c) and
      pFVC(v) correlated significantly with rFVC at 6 months after surgery (p=0.007 and
      0.006). Both the conventional and the volumetric methods provided FVC predictions
      that correlated significantly with measured postoperative FVC.

PMID- 21860534
TI  - Inhibitory effects of valproate on impairment of Y-maze alternation behavior
      induced by repeated electroconvulsive seizures and c-Fos protein levels in rat
      brains.
AB  - We previously showed that inhibition of repeated electroconvulsive shock (ECS)
      induced seizures through 7-day administration of anti-epileptic drugs suppressed
      the impairment of spontaneous alternation behavior in the Y-maze test in rats. To
      clarify the precise mechanism(s), we investigated the effect of valproate on such
      impairment and examined the levels of brain-derived neurotrophic factor (BDNF)
      and c-Fos protein in the prefrontal cortex and the hippocampus 24h after the last
      administration of ECS. Seven-day intraperitoneal (i.p.) administration of
      valproate (400mg/kg) suppressed the impairment of spontaneous alternation
      behavior. Repeated ECS increased the BDNF protein levels in the hippocampus and
      prefrontal cortex in the presence or absence of valproate, indicating that the
      increase in BDNF protein levels resulted from electrical stimulation. c-Fos
      protein levels were significantly decreased in the hippocampal dentate gyrus
      after repeated ECS, but valproate had no significant effect on decreased c-Fos
      protein levels. Valproate+ECS significantly increased the c-Fos protein levels of
      the prefrontal cortex compared with the ECS group. These findings suggest that
      the inhibitory effect of valproate on repeated ECS-induced impairment of
      spontaneous alternation behavior may be linked to the prefrontal cortex.

PMID- 21860535
TI  - Simulation of DNA Extension in Nanochannels.
AB  - We have used a realistic model for double stranded DNA and Monte Carlo
      simulations to compute the extension (mean span) of a DNA molecule confined in a
      nanochannel over the full range of confinement in a high ionic strength buffer.
      The simulation data for square nanochannels resolve the apparent contradiction
      between prior simulation studies and the predictions from Flory theory,
      demonstrating the existence of two transition regimes between weak confinement
      (the de Gennes regime) and strong confinement (the Odijk regime). The simulation
      data for rectangular nanochannels support the use of the geometric mean for
      mapping data obtained in rectangular channels onto models developed for
      cylinders. The comparison of our results with experimental data illuminates the
      challenges in applying models for confined, neutral polymers to polyelectrolytes.
      Using a Flory-type approach, we also provide an improved scaling result for the
      relaxation time in the transition regime close to that found in experiments.

PMID- 21860536
TI  - $100 Bills on the Sidewalk: Suboptimal Investment in 401(k) Plans.
AB  - We identify employees at seven companies whose 401(k) investment choices are
      dominated because they are contributing less than the employer matching
      contribution threshold despite being vested in their match and being able to make
      penalty-free 401(k) withdrawals for any reason because they are older than 591/2.
      At the average firm, 36% of match-eligible employees over 591/2 forego arbitrage
      profits that average 1.6% of their annual pay, or $507. A survey educating
      employees about the free lunch they are foregoing raised contribution rates by a
      statistically insignificant 0.67 percent of income among those completing the
      survey.

PMID- 21860537
TI  - Adolescent Girls' Assessment and Management of Sexual Risks: Insights from Focus
      Group Research.
AB  - We conducted focus groups with girls ages 14 to 17 (N = 43) in order to study how
      the dominant discourse of sexual risk shapes young women's understanding of the
      sexual domain and their management of these presumably pervasive threats. Through
      inductive analysis, we developed a coding scheme focused on three themes: (a)
      types of sexual risk; (b) factors that moderate sexual risk; and (c) strategies
      for managing sexual risk. Collectively, participants identified many risks but
      distanced themselves from these by claiming that girls' susceptibility is largely
      a function of personal factors and therefore avoidable given the right traits,
      values, and skills. We consider this reliance on other-blaming and self
      exemption, as well as instances in which individual participants diverged from
      this group discourse, in the context of neoliberalism.

PMID- 21860538
TI  - The Impact of NIH Postdoctoral Training Grants on Scientific Productivity.
AB  - In this paper, we estimate the impact of receiving an NIH postdoctoral training
      grant on subsequent publications and citations. Our sample consists of all
      applications for NIH postdoctoral training grants (unsuccessful as well as
      successful) from 1980 to 2000. Both ordinary least squares and regression
      discontinuity estimates show that receipt of an NIH postdoctoral fellowship leads
      to about one additional publication over the next five years, which reflects a 20
      percent increase in research productivity.

PMID- 21860539
TI  - Estimating age-specific incidence of dementia using prevalent cohort data.
AB  - In prospective cohort studies individuals are usually recruited according to a
      certain cross-sectional sampling criterion. The prevalent cohort is defined as a
      group of individuals who are alive but possibly with disease at the beginning of
      the study. It is appealing to incorporate the prevalent cases to estimate the
      incidence rate of disease before the enrollment. The method of back calculation
      of incidence rate has been used to estimate the incubation time from HIV
      infection to AIDS. The time origin is defined as the time of HIV infection. In
      aging cohort studies, the primary time scale is age of disease onset, subjects
      have to survive certain years to be enrolled into the study, thus creating left
      truncation (delay entry). The current methods usually assume that either the
      disease incidence is rare or the excess mortality due to disease is small
      compared to the healthy subjects. By far the validity of the results based on
      these assumptions has not been examined. In this paper, a simple alternative
      method is proposed to estimate dementia incidence rate before enrollment using
      prevalent cohort data with left truncation. Furthermore simulations are used to
      examine the performance of the estimation of disease incidence under different
      assumptions of disease incidence rates and excess mortality hazards due to
      disease. As application, the method is applied to the prevalent cases of dementia
      from the Honolulu Asia Aging Study to estimate dementia incidence rate and to
      assess the effect of hypertension, Apoe 4 and education on dementia onset.

PMID- 21860540
TI  - POLYELECTROLYTE MULTILAYER STAMPING IN AQUEOUS PHASE AND NON-CONTACT MODE.
AB  - Polyelectrolyte multilayer (PEM) transfer printing has been previously achieved
      by stamping under dry conditions. Here, we show for the first time, that PEM can
      be transferred from a stamp to the base substrate under aqueous conditions
      whereby the two surfaces are in a non-contact mode. Degradable multilayers of
      (PAA/PEG)(10.5) followed by non-degradable multilayers of (PDAC/SPS)(80.5) were
      fabricated under acidic pH conditions on either PDMS or glass (stamp), and
      subsequently transferred over top of another multilayer prepared on a different
      substrate (base substrate), with a spacing of ~ 200 MUm between the stamping
      surface and the base substrate. This multilayer transfer was performed under
      physiological pH conditions. This process is referred to herein as non-contact,
      aqueous-phase multilayer (NAM) transfer. NAM transfer can be useful for
      applications such as fabricating three-dimensional (3-D) cellular scaffolds. We
      attempted to create a 3-D cellular scaffold using NAM transfer, and characterized
      the scaffolds with conventional and fluorescence microscopy.

PMID- 21860541
TI  - A Case of Hemorrhagic Necrosis of Ectopic Liver Tissue within the Gallbladder
      Wall.
AB  - Ectopic liver tissue is a rare clinical entity that is mostly asymptomatic and
      found incidentally. In certain situations, however, patients may present with
      symptoms of abdominal pain secondary to torsion, compression, obstruction of
      adjacent organs, or rupture secondary to malignant transformation. Herein, we
      report a case of a 25-year-old female that presented with acute onset of
      epigastric pain found to have ectopic liver tissue near the gallbladder
      complicated by acute hemorrhage necessitating operative intervention in the way
      of laparoscopic excision and cholecystectomy. The patient's postoperative course
      was uneventful. Gross pathology demonstrated a 1.2 * 2.8 * 4.5 cm firm purple
      ovoid structure that histologically revealed extensive hemorrhagic necrosis of
      benign ectopic liver tissue.

PMID- 21860542
TI  - Capacitive micromachined ultrasonic transducers for medical imaging and therapy.
AB  - Capacitive micromachined ultrasonic transducers (CMUTs) have been subject to
      extensive research for the last two decades. Although they were initially
      developed for air-coupled applications, today their main application space is
      medical imaging and therapy. This paper first presents a brief description of
      CMUTs, their basic structure, and operating principles. Our progression of
      developing several generations of fabrication processes is discussed with an
      emphasis on the advantages and disadvantages of each process. Monolithic and
      hybrid approaches for integrating CMUTs with supporting integrated circuits are
      surveyed. Several prototype transducer arrays with integrated frontend electronic
      circuits we developed and their use for 2-D and 3-D, anatomical and functional
      imaging, and ablative therapies are described. The presented results prove the
      CMUT as a MEMS technology for many medical diagnostic and therapeutic
      applications.

PMID- 21860543
TI  - Deviations in circulating TNFalpha levels and TNFalpha production by mononuclear
      cells in healthy human populations.
AB  - OBJECTIVES: Tumor necrosis factor alpha (TNFalpha) plays a pivotal role in the
      inflammatory host response. The serum-level of TNFalpha and the production of
      TNFalpha by lympho/monocytes, however, seem to show high individual variations.
      The goal of the present study was to investigate the variations and inducibility
      of TNFalpha-activity in two age-groups of healthy volunteers. METHODS: Sixty
      elderly, healthy volunteers were studied. These persons were free of malignant
      diseases, and within three months, they did not have any trauma or inflammatory
      disease and were not taking any steroids or nonsteroid anti-inflammatory drugs.
      Thirty young volunteers were also included. Blood samples were taken;
      lympho/monocytes were separated and cultured with or without endotoxin (LPS)
      stimulation. Serum and culture supernatant TNFalpha levels were determined by
      bioassay using WEHI 164 cells. RESULTS: The results indicated significant
      individual variations in TNFalpha levels of healthy volunteers irrespective of
      age. Subgroups with low, middle, and high serum TNF-levels were distinguished. In
      about 50% of volunteers with low serum-TNFalpha activity, LPS stimulation failed
      to increase the TNFalpha production by isolated lympho/monocytes. CONCLUSION: Our
      data suggest a chance to select individuals with enhanced sensitivity for septic
      complications.

PMID- 21860544
TI  - Streptococcus pneumoniae type determination by multiplex polymerase chain
      reaction.
AB  - The purpose of this study was to develop pneumococcal typing by multiplex PCR and
      compare it with conventional serotyping by quellung reaction. Pneumococcal
      strains used in this study included 77 isolates from clinical specimens collected
      from children at Seoul National University Children's Hospital from 2006 to 2010.
      These strains were selected as they represented 26 different serotypes previously
      determined by quellung reaction. Molecular type was determined by 8 sequential
      multiplex PCR assays. Bacterial DNA extracted from cultured colonies was used as
      a template for PCR, and primers used in this study were based on cps operon
      sequences. Types 6A, 6B, 6C, and 6D were assigned based on the presence of
      wciN(beta) and/or wciP genes in 2 simplex PCRs and sequencing. All 77 isolates
      were successfully typed by multiplex PCR assays. Determined types were as
      follows: 1, 3, 4, 5, 6A, 6B, 6C, 6D, 7C, 7F, 9V, 10A, 11A, 12F, 13, 14, 15A,
      15B/15C, 19A, 19F, 20, 22F, 23A, 23F, 34, 35B, and 37. The results according to
      the PCR assays were in complete concordance with those determined by conventional
      quellung reaction. The multiplex PCR assay is highly reliable and potentially
      reduces reliance upon conventional serotyping.

PMID- 21860545
TI  - Risk factors of postoperative pneumonia after lung cancer surgery.
AB  - The purpose of this study was to investigate risk factors of postoperative
      pneumonia (POP) after lung cancer surgery. The 417 lung cancer patients who
      underwent surgical resection in a tertiary referral hospital were included.
      Clinical, radiological and laboratory data were reviewed retrospectively. Male
      and female ratio was 267:150 (median age, 65 yr). The incidence of POP was 6.2%
      (26 of 417) and in-hospital mortality was 27% among those patients. By univariate
      analysis, age >= 70 yr (P < 0.001), male sex (P = 0.002), ever-smoker (P <
      0.001), anesthesia time >= 4.2 hr (P = 0.043), intraoperative red blood cells
      (RBC) transfusion (P = 0.004), presence of postoperative complications other than
      pneumonia (P = 0.020), forced expiratory volume in 1 second/forced vital capacity
      (FEV(1)/FVC) < 70% (P = 0.002), diffusing capacity of the lung for carbon
      monoxide < 80% predicted (P = 0.015) and preoperative levels of serum C-reactive
      protein >= 0.15 mg/dL (P = 0.001) were related with risk of POP. Multivariate
      analysis showed that age >= 70 yr (OR = 3.563, P = 0.014), intraoperative RBC
      transfusion (OR = 4.669, P = 0.033), the presence of postoperative complications
      other than pneumonia (OR = 3.032, P = 0.046), and FEV(1)/FVC < 70% (OR = 3.898, P
      = 0.011) were independent risk factors of POP. In conclusion, patients with
      advanced age, intraoperative RBC transfusion, postoperative complications other
      than pneumonia and a decreased FEV(1)/FVC ratio have a higher risk for pneumonia
      after lung cancer surgery.

PMID- 21860546
TI  - Retroperitoneal fibrosis in 27 Korean patients: single center experience.
AB  - Retroperitoneal fibrosis (RPF) is a rare disease with unclear etiology, which is
      characterized by chronic non-specific inflammation of the retroperitoneum. This
      study was performed to investigate the clinical characteristics, laboratory
      findings, radiologic findings, treatment and outcome in Korean patients with RPF.
      We retrospectively reviewed medical records of 27 RPF patients who were admitted
      to Yonsei University Medical Center between 1998 and 2009. Twenty-two patients
      (81%) were male. The mean age at diagnosis was 56 yr. Nine patients had
      identifiable risk factors of RPF and three patients had combined autoimmune
      diseases. Acute phase reactants were elevated in most patients. Rheumatoid factor
      was positive in 3 of 16 patients (19%) and antinuclear antibody in 4 of 17 (24%).
      Five of 6 patients who were taken positron-emission tomography showed positive
      uptake. Glucocorticoids were used in 16 patients (59%) and four of them received
      combination therapy with azathioprine. After immunosuppressive treatment, the
      levels of acute phase reactants dropped, and the size of mass also decreased in
      most patients. In conclusion, the clinical characteristics of RPF in Korean
      patients are similar with other series except for higher proportion of male. Some
      patients with RPF have autoimmune features. The effect of immunosuppressive
      treatment on RPF is good.

PMID- 21860547
TI  - XRCC1 polymorphisms and risk of papillary thyroid carcinoma in a Korean sample.
AB  - Polymorphisms of DNA repair genes, X-ray repair cross-complementing group 1
      (XRCC1) might contribute to individual susceptibility to different types of
      cancers. We analyzed the relationship between XRCC1 polymorphisms and the risk of
      papillary thyroid carcinoma in a Korean sample. A hospital-based case-control
      study was performed in 111 papillary thyroid carcinoma patients and 100 normal
      control subjects. XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms
      (SNPs) were genotyped by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). The XRCC1 Arg194Trp Arg/Trp genotype was significantly
      associated with a decreased risk of papillary thyroid carcinoma compared to that
      of Arg/Arg genotype (odds ratio [95% confidence intervals]; 0.550 [0.308-0.983]).
      There was no significant association between XRCC1 Arg399Gln genotypes and risk
      of papillary thyroid carcinoma. Based on these results, the XRCC1 Arg194Trp
      Arg/Trp genotype could be used as a useful molecular biomarker to predict genetic
      susceptibility for papillary thyroid carcinoma in Koreans.

PMID- 21860548
TI  - A scoring system for prediction of lateral neck node metastasis from papillary
      thyroid cancer.
AB  - Lateral neck node metastasis is an important prognostic factor in thyroid
      carcinoma. We developed a scoring system for use in prediction of lateral neck
      node metastasis from papillary thyroid cancer. In this study, 161 consecutive
      patients were included in the training data set. This scoring system, named the
      Yonsei Estimated Value (YEV) for lymph node metastasis in papillary thyroid
      cancer, was developed on the basis of results from multivariate logistic
      regression analysis of preoperative clinical and radiologic data. Sixty eight
      consecutive patients were included for testing of the validity of the scoring
      system. The equation for prediction of lateral neck node metastasis was
      follows:YEV (Yonsei Estimated Value) = 1/(1+X)X = Exp (5.333-[0.902 * sex]+[0.036
      * age]-[1.020 * tumor size]-[0.177 * lymph node size]-[0.032 * lymph node
      density])When the YEV was 0.3 or more, the probability of lateral neck node
      metastasis was 79.0%, with sensitivity of 76.3%, specificity of 69.8%, positive
      predictive value of 56.7%, and negative predictive value of 85.1% in the training
      set. When fine needle aspiration biopsy for suspicious lateral neck nodes is not
      possible, or the results are inadequate, our scoring system for prediction of
      lateral neck node metastasis can be helpful in optimization of the surgical
      extent for each patient.

PMID- 21860549
TI  - Evaluation of intratumoral HER-2 heterogeneity by fluorescence in situ
      hybridization in invasive breast cancer: a single institution study.
AB  - This study aimed to determine the incidence and characteristics of HER-2 gene
      heterogeneity in invasive breast cancer in a single institution. Included were
      971 cases of primary invasive breast cancer diagnosed between 2008 and 2010.
      Fluorescence in situ hybridization (FISH) image files were retrospectively
      reviewed and HER-2 gene heterogeneity was defined as more than 5% but less than
      50% of analyzed invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2,
      according to the College of American Pathologists guidelines. HER-2 gene
      heterogeneity was identified in 24 (2.5%) cases. The mean proportion of invasive
      tumor cells with a HER-2/chromosome 17 ratio higher than 2.2 was 11.6% (range: 5%
      25%). Of 24 cases, HER-2 gene status was not amplified in 8, showed borderline
      amplification in 2, and amplification in 14. All HER-2 amplification cases were
      low-grade. In conclusion, HER-2 gene heterogeneity of invasive breast cancer is
      identified in routine FISH examination. This may affect the results of HER-2 gene
      amplification status in FISH studies.

PMID- 21860550
TI  - Association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer
      patients with tamoxifen treatment.
AB  - The aim of the study was to evaluate the association between genetic
      polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen
      treatment. We evaluated the CYP2D6 genetic polymorphisms in 766 breast cancer
      patients. Among them, 110 patients whose samples were prospectively collected
      before surgery and treated with tamoxifen were included to evaluate the
      association between CYP2D6 and outcomes. The genotypes of CYP2D6 were categorized
      as extensive metabolizer (EM), intermediate metabolizer (IM), and poor
      metabolizer (PM) according to the activity score. The clinicopathologic features
      of 110 patients were not significantly different among the three groups except
      for the T-stage and nodal status. The high T-stage and axillary metastasis were
      more frequent in the PM group. While recurrence-free and overall survival in the
      PM group was poorer than the other groups, there was no significant difference
      between the EM and the IM group. The difference between the PM and the other
      groups on univariate analysis disappeared on multivariate analysis. These
      conflicting results suggest that the clinical value of CYP2D6 polymorphisms is
      still unclear and more large-sized and comprehensively designed trials are
      necessary.

PMID- 21860551
TI  - Prognostic index for portal vein tumor thrombosis in patients with hepatocellular
      carcinoma treated with radiation therapy.
AB  - We performed a retrospective review of 281 hepatocellular carcinoma (HCC)
      patients with portal vein tumor thrombosis (PVTT) treated with radiation therapy
      (RT) between 1998 and 2008 to develop a prognostic model for those patients. Of
      the 281 patients, PVTT and intrahepatic main masses completely disappeared in 10
      patients (3.6%), and shown a partial response in 141 patients (50.2%). The median
      survival was 11.6 months. Patients who had more than PR have shown significantly
      longer survival than the others (22.0 months vs 5.0 months, P < 0.001). On the
      multivariate analysis, pre-treatment poor prognosticators for overall survival
      were ECOG performance status, Child-Pugh class, multiple tumors, main PVTT,
      complete portal vein occlusion, lymph node metastasis, and primary tumor size.
      Prognostic index of RT for PVTT of HCC (PITH) scores were defined as the number
      of pre-treatment poor prognostic factors. PITH scores correlated well with
      overall survival. In the analysis of 1 and 2 yr overall survival rate, patients
      who had PITH scores of 3 or greater showed a significantly lower rate of overall
      survival than the others (33.0%, 17.3% vs 70.1%, 40.8%, respectively, P < 0.001).
      The PITH scoring model, proposed in the current study in HCC patients with PVTT,
      reliably predict overall survival.

PMID- 21860552
TI  - Clinicopathologic study on combined hepatocellular carcinoma and
      cholangiocarcinoma: with emphasis on the intermediate cell morphology.
AB  - Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a
      rare subtype of primary liver cancer. We investigated the histopathologic
      features of transitional or intermediate areas in 21 combined HCC-CCs and
      immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c
      kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate
      areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval
      shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an
      abundant stroma, small cells with an antler-like anastomosing pattern, and solid
      nests of intermediate hepatocyte-like cells surrounded by small cells in
      periphery, in order of frequency. The intermediate area of one tumor was composed
      predominantly of spindle cells arranged in short fascicles. Immunophenotype of
      tumor cells with intermediate morphology suggested a progenitor cell origin for
      this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with
      those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and
      serum alpha-fetoprotein levels showed a significant association with poor patient
      survival. Serum alpha-fetoprotein level was an independent prognostic indicator
      in multivariate analysis. In conclusion, an awareness of the clinicopathologic
      features, specifically the various morphologic features of intermediate areas in
      this tumor, is essential for prevention of potential misdiagnosis as another
      tumor.

PMID- 21860553
TI  - Comparing two-stent strategies for bifurcation coronary lesions: which vessel
      should be stented first, the main vessel or the side branch?
AB  - This study compared two-stent strategies for treatment of bifurcation lesions by
      stenting order, 'main across side first (A-family)' vs 'side branch first (S
      family). The study population was patients from 16 centers in Korea who underwent
      drug eluting stent implantation with two-stent strategy (A-family:109, S
      family:140 patients). The endpoints were cardiac death, myocardial infarction
      (MI), stent thrombosis (ST), and target lesion revascularization (TLR) during 3
      years. During 440.8 person-years (median 20.2 months), there was 1 cardiac death,
      4 MIs (including 2 STs), and 12 TLRs. Cumulative incidence of cardiac death, MI
      and ST was lower in A-family (0% in A-family vs 4.9% in S-family, P = 0.045).
      However, TLR rates were not different between the two groups (7.1% vs 6.2%, P =
      0.682). Final kissing inflation (FKI) was a predictor of the hard-endpoint
      (hazard ratio 0.061; 95% CI 0.007-0.547, P = 0.013), but was not a predictor of
      TLR. The incidence of hard-endpoint of S-family with FKI was comparable to A
      family, whereas S-family without FKI showed the poorest prognosis (1.1% vs 15.9%,
      retrospectively; P = 0.011). In conclusion, 'A-family' seems preferable to 'S
      family' if both approaches are feasible. When two-stent strategy is used, every
      effort should be made to perform FKI, especially in 'S-family'.

PMID- 21860555
TI  - Suitability of endovascular repair with current stent grafts for abdominal aortic
      aneurysm in Korean patients.
AB  - Suitability rate of endovascular aneurysm repair (EVAR) and the anatomic features
      causing unsuitability have not been well determined in Asian patients who have
      abdominal aortic aneurysm (AAA). In a single Korean center, a total of 191
      patients with abdominal aortic aneurysm (maximal diameter >= 4 cm) were
      identified. Aortoiliac morphologic characteristics in contrast-enhanced computed
      tomography images were retrospectively reviewed to determine suitability for EVAR
      with four FDA-approved stent-grafts. AAA was considered ideally suitable for EVAR
      in 46.6% of patients. The most frequent causes for unsuitability were common
      iliac artery (CIA) aneurysm (61.8%) and excessive neck angulation (52.9%).
      Problems such as small and/or short neck and small access were found in minor
      incidences. If CIA aneurysm is dealt by overstenting with sacrifice of internal
      iliac artery, suitability rate can increase to 65%. Larger aneurysms were more
      frequently unsuitable for EVAR and had more chance of having multiple unfavorable
      features. In conclusion, the overall feasibility rate for EVAR in Korean patients
      was not different from that in Western patients. However, considering the
      difference in the major causes of unsuitability, more attention has to be paid to
      neck angulation and CIA aneurysm to provide EVAR for more Korean patients
      especially who have large aneurysm.

PMID- 21860554
TI  - Preoperative aspirin resistance does not increase myocardial injury during off
      pump coronary artery bypass surgery.
AB  - We performed a prospective cohort trial on 220 patients undergoing elective off
      pump coronary artery bypass surgery and taking aspirin to evaluate the effect of
      aspirin resistance on myocardial injury. The patients were divided into aspirin
      responders and aspirin non-responders by the value of the aspirin reaction units
      obtained preoperatively using the VerifyNowTM Aspirin Assay. The serum levels of
      troponin I were measured before surgery and 1, 6, 24, 48 and 72 hr after surgery.
      In-hospital major adverse cardiac and cerebrovascular events, graft occlusion,
      the postoperative blood loss and reexploration for bleeding were recorded. Of the
      220 patients, 181 aspirin responders (82.3%) and 39 aspirin non-responders
      (17.7%) were defined. There were no significant differences in troponin I levels
      (ng/mL) between aspirin responders and aspirin non-responders: preoperative (0.04
      +/- 0.08 vs 0.03 +/- 0.06; P = 0.56), postoperative 1 hr (0.72 +/- 0.87 vs 0.86
      +/- 1.10; P = 0.54), 6 hr (2.92 +/- 8.76 vs 1.50 +/- 2.40; P = 0.94), 24 hr (4.16
      +/- 13.44 vs 1.25 +/- 1.95; P = 0.52), 48 hr (2.15 +/- 7.06 vs 0.65 +/- 0.95; P =
      0.64) and 72 hr (1.20 +/- 4.63 vs 0.38 +/- 0.56; P = 0.47). Moreover, no
      significant differences were observed with regard to in-hospital outcomes. In
      conclusion, preoperative aspirin resistance does not increase myocardial injury
      in patients undergoing off-pump coronary artery bypass surgery. Postoperative
      dual antiplatelet therapy might have protected aspirin resistant patients.

PMID- 21860556
TI  - Relationship between coronary artery calcium score by multidetector computed
      tomography and plaque components by virtual histology intravascular ultrasound.
AB  - The aim of this study was to evaluate the relationship between coronary artery
      calcium score (CACS) assessed by multidetector computed tomography (MDCT) and
      plaque components assessed by virtual histology-intravascular ultrasound (VH
      IVUS) in 172 coronary artery disease (CAD) patients with 250 coronary lesions.
      CACS was assessed according to Agatston scoring method by MDCT and patients were
      divided into four groups: Group I (CACS = 0 [n = 52]); Group II (CACS = 1-100 [n
      = 99]); Group III (CACS = 101-400 [n = 84]); and Group IV (CACS > 400 [n = 15]).
      Total atheroma volume was greatest in Group IV (152 +/- 132 uL vs 171 +/- 114 uL
      vs 195 +/- 149 uL vs 321+/-182 uL, P < 0.001). The absolute dense calcium (DC)
      and necrotic core (NC) volumes were greatest, and relative DC volume was greatest
      in Group IV (5.5 +/- 6.6 uL vs 11.0 +/- 10.3 uL vs 15.6 +/- 13.6 uL vs 36.6 +/-
      18.2 uL, P < 0.001, and 14.8 +/- 18.2 uL vs 19.5 +/- 18.9 uL vs 22.5 +/- 19.1 uL
      vs 41.7 +/- 27.9 uL, P < 0.001, and 6.4 +/- 5.3% vs 11.0 +/- 6.2% vs 14.0 +/-
      6.5% vs 20.0 +/- 7.8%, P < 0.001, respectively). The absolute plaque and DC and
      NC volumes and the relative DC volume correlated positively with calcium score.
      CAD patients with high calcium score have more vulnerable plaque components
      (greater DC and NC-containing plaques) than those with low calcium score.

PMID- 21860557
TI  - Characteristics of sodium sensitivity in Korean populations.
AB  - Sodium sensitivity (SS) is a variable response of blood pressure (BP) to changes
      in sodium intake. The present study evaluated the existence and the
      characteristics of subjects with SS in Koreans. One hundred one subjects with (n
      = 31, 57.7 +/- 9.8 yr) or without hypertension (n = 70, 40.8 +/- 16.5 yr) were
      given a low-sodium dietary approache to stop hypertension (DASH) diet (LSD) for 7
      days and a high-sodium DASH diet (HSD) for the following 7 days. The prevalence
      of SS in the present study population was 27.7% (17.6% in the non-hypertensive
      subjects and 51.6% in the hypertensive subjects). Analysis of the non
      hypertensive subjects showed that systolic BP, diastolic BP, and mean arterial
      pressure at baseline and after HSD were higher in the subjects with SS than the
      subjects without SS, and there were no differences after LSD. In the hypertensive
      subjects, there was no difference in the BP at baseline and after HSD whether or
      not the subjects had SS. However, the systolic BP of hypertensive subjects with
      SS was lower than hypertensive subjects without SS after LSD. In the present
      study population, subjects with SS have distinctive BP features unlike to
      subjects without SS.

PMID- 21860558
TI  - Prevalence and associated factors of diabetic retinopathy in rural Korea: the
      Chungju metabolic disease cohort study.
AB  - This study was aimed to investigate the prevalence of diabetic retinopathy and
      its associated factors in rural Korean patients with type 2 diabetes. A
      population-based, cross-sectional diabetic retinopathy survey was conducted from
      2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes
      identified in a rural area of Chungju, Korea. Diabetic retinopathy was diagnosed
      by a practicing ophthalmologist using funduscopy. The overall prevalence of
      diabetic retinopathy in the population was 18% and proliferative or severe non
      proliferative form was found in 5.0% of the study subjects. The prevalence of
      retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of
      them had a proliferative or severe non-proliferative diabetic retinopathy. The
      odds ratio of diabetic retinopathy increased with the duration of diabetes
      mellitus (5-10 yr: 5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (>
      180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The
      overall prevalence of diabetic retinopathy in rural Korean patients was similar
      to or less than that of other Asian group studies. However, the number of
      patients with proliferative or severe non-proliferative diabetic retinopathy was
      still high and identified more frequently at the time of diagnosis. This
      emphasizes that regular screening for diabetic retinopathy and more aggressive
      management of glycemia can reduce the number of people who develop diabetic
      retinopathy.

PMID- 21860559
TI  - Prevention of NSAID-associated gastroduodenal injury in healthy volunteers-a
      randomized, double-blind, multicenter study comparing DA-9601 with misoprostol.
AB  - In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti
      inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive
      oxygen species produced by recruited inflammatory cells. DA-9601 is a novel
      antioxidant with anti-inflammatory and cyto-protective effects. This study was
      conducted to compare the efficacy and safety of DA-9601 with misoprostol for
      preventing NSAID-associated gastroduodenal injury. In this randomized, double
      blind, multicenter, noninferiority trial we compared the extents of protection of
      gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601
      60 mg or misoprostol 200 ug three times daily, in subjects with normal baseline
      endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266
      subjects were randomized to treatment. At week 4, the gastric protection rates
      with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference
      between the groups was -10.1% (var = 0.001), which was shown to indicate
      noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in
      the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group,
      69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol
      for preventing NSAID-associated gastroduodenal injury, and superior to it with
      respect to treatment-related side effects.

PMID- 21860560
TI  - Effects of hepatocyte growth factor on collagen synthesis and matrix
      metalloproteinase production in keloids.
AB  - Keloids are pathologic proliferations of the dermal layer of the skin resulting
      from excessive collagen production and deposition. Hepatocyte growth factor (HGF)
      increases the expression of matrix metalloproteinase (MMP)-1 and suppresses
      collagen synthesis to modulate extracellular matrix turnover. To investigate the
      anti-fibrotic effects of HGF, we examine the mRNA expression of collagen types I
      and III and matrix metalloproteinase (MMP-1, MMP-3) on human dermal fibroblast
      (HDF) cell lines and keloid fibroblasts (KFs, n = 5) after adding various amount
      of HGF protein. We also evaluated the enzymatic activity of MMP-2, MMP-9 by
      zymograghy. In HDFs treated with TGF-beta1 and HGF protein simultaneously, both
      type I and III collagen mRNA expression significantly decreased (P < 0.05).
      Expression of MMP-1, MMP-3 mRNA also decreased. However, the mRNA expression of
      MMP-1, MMP-3 significantly increased in KFs with increasing amount of HGF in dose
      dependent manner (P < 0.05). The enzymatic activities of MMP-2 increased with
      increasing HGF protein in a dose-dependent manner. However, the enzymatic
      activity of MMP-9 did not change. These results suggest that the anti-fibrotic
      effects of HGF may have therapeutic effects on keloids by reversing pathologic
      fibrosis.

PMID- 21860561
TI  - Incidence and mortality following hip fracture in Korea.
AB  - The authors evaluated the incidence of hip fracture and subsequent mortality in
      Korea using nationwide data obtained from the Health Insurance Review and
      Assessment Service. This study was performed on patient population, aged 50-yr or
      older who underwent surgical procedures because of hip fracture (ICD10; S720,
      S721). All patients were followed using patient identification code to identify
      deaths. Crude hip fracture rates increased from 191.9/100,000 in 2005 to
      207.0/100,000 in 2008 in women and from 94.8/100,000 in 2005 to 97.8/100,000 in
      2008, in men respectively. Crude mortality within 12 months after hip fracture
      showed a similar trend (18.8% in 2005 and 17.8% in 2007). The mean of
      standardized mortality ratio of hip fracture was 6.1 at 3 months, 3.5 at 1 yr,
      and 2.3 at 2 yr post-fracture. The increasing incidence and the high mortality
      after hip fracture are likely to become serious public health problems and a
      public health program should begin to prevent hip fractures in Korea.

PMID- 21860562
TI  - Vitamin K supplement along with vitamin D and calcium reduced serum concentration
      of undercarboxylated osteocalcin while increasing bone mineral density in Korean
      postmenopausal women over sixty-years-old.
AB  - There are inconsistent findings on the effects of vitamin K on bone mineral
      density (BMD) and undercarboxylated osteocalcin (UcOC). The present intervention
      study evaluated the effect in subjects over 60-yr-old. The vitamin K group
      (vitamin K + vitamin D + calcium supplement; 15 mg of vitamin K2 [menatetrenone]
      three times daily, 400 IU of vitamin D once a day, and 315 mg of calcium twice
      daily) and the control group (vitamin D + calcium supplement) were randomly
      assigned. During the six months of treatment, seventy eight women participated
      (38 in the vitamin K group and 40 in the control group) and 45 women completed
      the study. The baseline characteristics of study participants did not differ
      between the vitamin K and the control groups. In a per protocol analysis after 6
      months, L3 bone mineral density has increased statistically significantly in the
      vitamin K group compared to the control group (0.01 +/- 0.03 g/cm(2) vs -0.008 +/
      0.04 g/cm(2), P = 0.049). UcOC concentration was also significantly decreased in
      the vitamin K group (-1.6 +/- 1.6 ng/dL vs -0.4 +/- 1.1 ng/dL, P = 0.008). In
      conclusion, addition of vitamin K to vitamin D and calcium supplements in the
      postmenopausal Korean women increase the L3 BMD and reduce the UcOC
      concentration.

PMID- 21860563
TI  - Development of acute megakaryoblastic leukemia with isochromosome (12p) after a
      primary mediastinal germ cell tumor in Korea.
AB  - The association of hematological malignancies with a mediastinal germ cell tumor
      (GCT) is very rare. We report one case of a young adult male with primary
      mediastinal GCT who subsequently developed acute megakaryoblastic leukemia
      involving isochromosome (12p). A 25-yr-old man had been diagnosed with a
      mediastinal GCT and underwent surgical resection and adjuvant chemotherapy. At 1
      week after the last cycle of chemotherapy, his peripheral blood showed
      leukocytosis with blasts. A bone marrow study confirmed the acute
      megakaryoblastic leukemia. A cytogenetic study revealed a complex karyotype with
      i(12p). Although additional chemotherapy was administered, the patient could not
      attain remission and died of septic shock. This case was definitely distinct from
      therapy-related secondary leukemia in terms of clinical, morphologic, and
      cytogenetic features. To our knowledge, this is the first case report of a
      patient with mediastinal GCT subsequently developing acute megakaryoblastic
      leukemia involving i(12p) in Korea.

PMID- 21860564
TI  - Fulminant Epstein-Barr virus-associated T-cell lymphoproliferative disorder in an
      immunocompetent middle-aged man presenting with chronic diarrhea and
      gastrointestinal bleeding.
AB  - The World Health Organization (WHO) recently defined systemic Epstein-Barr virus
      (EBV)-positive T-cell lymphoproliferative disorders (LPD) of childhood as a life
      threatening illness. However, this rare disease has not been extensively studied.
      Here we report a case of systemic EBV-positive T-cell LPD in a previously healthy
      middle-aged man with a chief complaint of chronic diarrhea. The initial colon
      biopsy showed focal infiltration of EBV-positive small lymphocytes without any
      atypia. However, the disease rapidly progressed and the patient required a total
      colectomy due to severe gastrointestinal bleeding. Three and half months after
      admission, the patient died from a complication of disseminated intravascular
      coagulation. The resected colon showed diffuse infiltration of EBV-positive
      atypical lymphocytes with ischemic change. Most atypical lymphocytes were CD3+ or
      CD5+. The monoclonality of EBV was demonstrated by sequence variation analysis of
      the latent membrane protein 1 (LMP1) gene in the colectomy specimen as well as in
      the initial biopsy.

PMID- 21860565
TI  - A case of hepatic portal venous gas as a complication of endoscopic balloon
      dilatation.
AB  - The development of hepatic portal venous gas (HPVG) is rare but it might be
      associated with serious disease and poor clinical outcome. Recently, several
      iatrogenic causes of HPVG have been reported. HPVG as a complication of
      endoscopic balloon dilatation is a previously unreported event. We experienced a
      case of HPVG after endoscopic balloon dilatation in a 31 yr-old man with pyloric
      stricture due to corrosive acids ingestion. The patient was treated
      conservatively with fluid resuscitation, antibiotics and Levin tube with natural
      drainage. Five days later, the follow-up CT scan showed spontaneous resolution of
      HPVG. This case reminded us the clinical importance and management strategy of
      HPVG. We report here a case of iatrogenic HPVG with a review of relevant
      literature.

PMID- 21860566
TI  - Novel compound heterozygous mutations in the vitamin D receptor gene in a Korean
      girl with hereditary vitamin D resistant rickets.
AB  - Hereditary vitamin D resistant rickets (HVDRR) is a rare genetic disorder caused
      by a mutation of vitamin D receptor (VDR) gene. A number of cases had been
      reported in many countries but not in Korea. We examined a three-year old Korean
      girl who had the typical clinical features of HVDRR including rickets,
      hypocalcemia, hypophosphatemia, elevated serum calcitriol level and secondary
      hyperparathyroidism. The girl and her father were both heterozygous for the 719C
      to-T(I146T)---> c.437C > T(p.T1461) [corrected] mutation in exon 4, whereas she
      and her mother were both heterozygous for 754C-to-T (R154C)---> c.472 >
      T(p.R158C) [corrected] mutation in exon 5 of the VDR gene. In this familial
      study, we concluded that the girl had compound heterozygous mutations in her VDR
      gene which caused HVDRR. This is the first report of a unique mutation in the VDR
      gene in Korea.

PMID- 21860567
TI  - Clinical features of idiopathic juxtafoveal telangiectasis in Koreans.
AB  - PURPOSE: To describe the clinical characteristics of idiopathic juxtafoveal
      telangiectasis (IJT) in Koreans. METHODS: Medical records of 16 patients with IJT
      were analyzed during the period from 1997 to 2009. Diagnosis was based on
      biomicrosopic and fluorescein angiographic findings and the group was determined
      according to the Gass and Blodi classification. RESULTS: We analyzed eight
      patients in group 1A (50%), two in group 1B (12.5%), and six in group 2A (37.5%).
      Diverse treatment modalities, such as macular laser photocoagulation,
      photodynamic therapy, intravitreal antiangiogenic agent, and steroid injection,
      were applied for macular edema in nine eyes; however, only two eyes showed visual
      improvement. CONCLUSIONS: In this case series, group 1A was the most common. For
      macular edema related to IJT, current treatment strategies had no consistent
      effect.

PMID- 21860568
TI  - Combined treatment of photodynamic therapy and bevacizumab for choroidal
      neovascularization secondary to age-related macular degeneration.
AB  - PURPOSE: To evaluate the outcome of a combined photodynamic therapy and
      intravitreal injection of bevacizumab in choroidal neovascularization secondary
      to age-related macular degeneration. METHODS: Photodynamic therapy (PDT) was
      administered to 28 eyes followed by 3 consecutive bevacizumab injections.
      Patients were followed-up for more than 12 months. At baseline, 1, 3, 6, and 12
      months post PDT, visual acuity (VA) and central macular thickness were measured
      using optical coherence tomography. RESULTS: The mean VA was significantly
      improved from logarithm of the minimal angle of resolution 0.86 at baseline to
      0.69 at 1 month (p = 0.011), 0.63 at 3 months (p = 0.003), 0.64 at 6 months (p =
      0.004) and 0.60 at 12 months (p < 0.001). Central macular thickness decreased
      significantly from 328.3 um at baseline to 230.0 um at 6 months and 229.9 um at 1
      year (p < 0.001). Reinjection mean number was 0.4 for 6 months and 0.8 for 12
      months. By 1 year, retreatment was performed in 10 eyes (36%). CONCLUSIONS: PDT
      combined with three consecutive intraviteal bevacizumab injections was effective
      in improving VA and reducing central macular thickness.

PMID- 21860569
TI  - Evaluation of changes of macular thickness in diabetic retinopathy after cataract
      surgery.
AB  - PURPOSE: To assess the macular thickness changes after cataract surgery in
      diabetic patients using optical coherence tomography (OCT). METHODS: We
      retrospectively reviewed the records of 104 diabetic patients who underwent
      cataract surgery. We examined the changes of macular thickness using OCT before
      cataract surgery and 1 week, 1-, 2- and 6-months after surgery. The central
      subfield mean thickness (CSMT) was used to evaluate macular edema which was
      defined as an increase of CSMT (DeltaCSMT) > 30% from the baseline. The
      association between prior laser treatment or severity of diabetic retinopathy and
      macular thickness were also analyzed. RESULTS: Macular edema occurred in 19 eyes
      (18%) from the diabetic group and 63% of macular edema developed at 1 month after
      surgery. Thirteen (68%) out of 19 eyes with macular edema showed the resolution
      of macular edema by 6 months after surgery without treatment. DeltaCSMT of eyes
      without a history of laser treatment was statistically greater compared to eyes
      with a history of laser treatment in at 1- and 2-months after surgery, but was
      not different than eyes who had laser treatment at 6-months after surgery. The
      severity of diabetic retinopathy was not significantly correlated to macular
      edema, but there was statistical difference when patients who had a history of
      prior laser treatment were excluded. CONCLUSIONS: The incidence of macular edema
      after cataract surgery in diabetic patients was 18%. Its peak incidence was at 1
      month post surgery and it resolved spontaneously in 68% of patients by 6 months
      post surgery. Prior laser treatment might prevent postoperative macular edema
      until 2 months after cataract surgery in diabetic patients. However, macular
      edema did not affect the severity of diabetic retinopathy.

PMID- 21860571
TI  - Attenuated age-related thinning of peripapillary retinal nerve fiber layer in
      long eyes.
AB  - PURPOSE: To assess the impact of axial length on the age-related peripapillary
      retinal nerve fiber layer (RNFL) thinning. METHODS: This cross-sectional
      observational comparative case series included 172 eyes from 172 healthy Korean
      subjects. Peripapillary RNFL thickness was measured using an Optic Disc Cube 200
      * 200 scan of spectral domain Cirrus HD OCT and the axial length was measured
      using IOL Master Advanced Technology. In age groups based on decade, the normal
      ranges of peripapillary RNFL thickness for average, quadrant, and clock-hour
      sectors were determined with 95% confidence intervals. After dividing the eyes
      into two groups according to axial length (cut-off, 24.50 mm), the degrees of age
      related RNFL thinning were compared. RESULTS: Among the eyes included in the
      study, 53 (30.81%) were considered to be long eyes (axial length, 25.04 +/- 0.48
      um) and 119 (69.19%) were short-to-normal length eyes (axial length, 23.57 +/-
      0.60 um). The decrease in average RNFL thickness with age was less in long eyes
      (negative slope, -0.12 um/yr) than in short-to-normal length eyes (negative
      slope, -0.32 um/yr) (p < 0.001). CONCLUSIONS: Age-related thinning of
      peripapillary RNFL thickness is attenuated in long eyes compared to short-to
      normal length eyes.

PMID- 21860570
TI  - Macular gradient measurement in myopic posterior staphyloma using optical
      coherence tomography.
AB  - PURPOSE: To evaluate clinical characteristics and the macular gradient in myopic
      posterior staphyloma with time domain (TD) optical coherence tomography (OCT).
      METHODS: Sixty-four staphyloma eyes of 40 patients were examined. Macular
      gradient (tangent theta) and the location of staphyloma were assessed with OCT
      imaging. The macular gradient was measured at points 1 mm and 2 mm distant from
      the fovea. The relationships of the macular gradient with age, axial length, and
      spherical equivalent were analyzed. RESULTS: In 8 eyes (12.5%), the bottoms of
      the staphylomas were in the fovea, and there was no macular gradient. However, in
      the other 56 eyes (87.5%), the bottoms of the staphylomas were not in the foveal
      area, and macular gradients existed. Staphylomas were commonly located in the
      infero-nasal retinal area. The mean macular gradient (tangent theta) was 0.26 +/-
      0.08 at 1 mm distance from the fovea and 0.28 +/- 0.10 at 2 mm. No significant
      relationships were observed between macular gradient and axial length, patient
      age, or spherical equivalent. CONCLUSIONS: TD OCT reveals staphyloma location. If
      the location is outside of the fovea, a macular gradient exists and can be
      measured by OCT. Axial length measurement error may occur in eyes with poor
      visual fixation and steep macular gradients.

PMID- 21860572
TI  - Laser peripheral iridotomy with iridoplasty in primary angle closure suspect:
      anterior chamber analysis by pentacam.
AB  - PURPOSE: To compare conventional laser peripheral iridotomy (LPI) and LPI
      combined with laser peripheral iridoplasty in eyes with primary angle closure
      suspect (PACS) by assessment of anterior chamber dimensional changes using a
      Pentacam. METHODS: Forty-eight eyes of 24 subjects with bilateral PACS were
      recruited consecutively. Each eye was randomly allocated to treatment with
      conventional LPI, argon LPI only, or LPI plus iridoplasty, which consisted of
      simultaneous argon LPI and peripheral iridoplasty. Anterior chamber measurements
      were performed on each eye using a Pentacam, both before and after treatment.
      Mean anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior
      chamber angle were measured, and topographic ACD analysis was performed. Results
      were compared between the two treatment groups. RESULTS: After treatment with
      either conventional LPI or LPI plus iridoplasty, the mean ACD and ACV increased
      significantly. Topographic ACD analysis revealed that the mid-to-peripheral ACD
      increase was significantly greater in the LPI plus iridoplasty group than in eyes
      treated with conventional LPI. Intraocular pressure changes and post-LPI
      complications did not differ between the groups. CONCLUSIONS: Compared with
      conventional LPI, our study showed that LPI plus iridoplasty improved the mid-to
      peripheral ACD increase. This procedure may have a role as an adjunct for
      reducing angle closure by simultaneously eliminating pupillary and non-pupillary
      block components.

PMID- 21860573
TI  - Amblyopia and strabismus by monocular corneal opacity following suspected
      epidemic keratoconjunctivitis in infancy.
AB  - PURPOSE: To identify the long term clinical course of amblyopia and strabismus
      that developed secondary to a monocular corneal opacity following suspected
      epidemic keratoconjunctivitis (EKC) in infancy. METHODS: This was a retrospective
      study analyzing the medical records of seven patients, treated in our clinic, who
      were followed for more than five years. RESULTS: Four patients in our clinic
      underwent a corneal ulcer treatment following suspected EKC. Each developed a
      monocular corneal opacity. Three patients with a chief complaint of corneal
      opacity were transferred to our clinic from other clinics. These patients had
      documented histories of treatment for EKC in infancy. All patients were treated
      with early occlusion therapy, but amblyopia persisted in four patients.
      Furthermore, all patients had strabismus and showed a significant reduction of
      stereoscopic vision. CONCLUSIONS: Although infants with EKC are not always
      cooperative, slit lamp examination should be performed as early as possible, and
      appropriate medical treatment should be performed, thus reducing the development
      of corneal opacity. Careful follow up should be regularly performed, and the
      occurrence of amblyopia or strabismus should be verified at an early stage using
      visual acuity or ocular alignment examination. Ophthalmologic treatments,
      including active occlusion therapy, should also be pursued.

PMID- 21860574
TI  - Evaluation of the central macula in commotio retinae not associated with other
      types of traumatic retinopathy.
AB  - PURPOSE: To report on the anatomical and functional changes to the macula in nine
      patients suffering from commotio retinae not accompanied by any other types of
      traumatic retinopathy. METHODS: Nine injured eyes with commotio retinae were
      evaluated soon after ocular trauma with ophthalmic examination, including
      Spectral-domain optical coherence tomography (SD-OCT). In 12 eyes of 6 patients,
      Humphrey visual field (HVF) and multifocal electroretinogram (mfERG) were
      performed. Re-examinations were periodically performed for a mean of 26 days.
      Data from 9 injured eyes were collected and compared to data collected from the 9
      non-affected eyes of the same patients. RESULTS: SD-OCT revealed no significant
      differences in the foveal thickness and total macular volume between traumatized
      and intact eyes in all 9 patients. Only 3 out of the 9 injured eyes showed
      abnormal findings in SD-OCT images such as discontinuity of the inner/outer
      segment (IS/OS) junction or abnormal hyper-reflectivity from the IS/OS and
      retinal pigment epithelium (RPE) lines in the macula. HVF and mfERG results did
      not show any functional deterioration in the injured eyes compared with intact
      eyes. During follow-up, the commotio retinae resolved in all 9 eyes. The changes
      to the outer retinal region detected in 3 patients by SD-OCT were also resolved.
      CONCLUSIONS: Acute retinal changes in commotio retinae, not associated with other
      retinal pathologies, were resolved without histological and functional sequelae.
      In a few cases of commotio retinae, SD-OCT revealed transient abnormalities
      mainly observed at the IS/OS and RPE complexes.

PMID- 21860575
TI  - Modulation of retinal wound healing by systemically administered bone marrow
      derived mesenchymal stem cells.
AB  - PURPOSE: To evaluate whether systemically injected bone marrow-derived
      mesenchymal stem cells (MSCs) can be incorporated into neuroretinal tissues and
      play an important role in retinal wound healing in the laser-induced retinal
      trauma model. METHODS: Retinotomies were made by applying an Nd:YAG laser to rat
      retina. On the first day after the injuries, cell suspensions that were obtained
      from the same line of rat (containing 1 * 10(6) green fluorescence protein [GFP]
      marked bone marrow-derived MSCs) were injected through a tail vein in the
      experimental group and phosphate buffer solution (PBS) was injected in the same
      way in the control group. Fundus photographs were taken serially for fundus
      examination and eyeballs were enucleated for histological studies that were
      conducted at five and seven weeks after MSC and PBS injection. After the tissues
      were prepared, the retinotomy sites were observed with routine histological
      staining and confocal microscopy. RESULTS: Retinal detachment resolved in the
      experimental group, whereas it progressed in the control group. The retinotomy
      sites closed partially with identifiable GFP positive cells 5 weeks after MSC
      injection. At 7 weeks after MSC injection, complete healing without retinal
      detachment and plentiful GFP positive cells were observed at the transitional
      zone between damaged and normal retina. CONCLUSIONS: Systemically administered
      GFP-marked MSCs may be incorporated into the neuroretinal tissues and play an
      important role in the wound modulation of physically damaged retinal tissues.

PMID- 21860576
TI  - A case of necrotizing keratoscleritis in primary Sjogren's syndrome.
AB  - We report on a case of necrotizing keratoscleritis in primary Sjogren's syndrome.
      A 66-year-old female patient who was complaining of ocular pain, tearing and
      decreased vision in her right eye for the previous two days was admitted to our
      hospital. Visual acuity in the right eye was hand movement, and initial
      examination showed a 3.0 * 1.8 mm uveal mass bulging through a corneoscleral
      melting site in the nasal region of the right eye. Positive anti-nuclear antibody
      was identified at a titer of 1:320 with a speckled pattern, and both Sjogren's
      syndrome A and Sjogren's syndrome B antibody tests were positive, with titers
      >200 U/mL. A technetium 99m pertechnetate salivary scan revealed chronic
      sialoadenitis in the submandibular glands. We diagnosed the lesion as necrotizing
      keratoscleritis due to primary Sjogren's syndrome. A corneoscleral patch graft
      was performed, followed by immunosuppression including oral cyclosporin and
      topical prednisolone. During a follow-up period of 12 months, the corneoscleral
      graft was well maintained with no recurrence.

PMID- 21860577
TI  - Comparison of spectral-domain and time-domain optical coherence tomography in
      solar retinopathy.
AB  - The purpose of this article is to compare spectral-domain (SD) and time-domain
      (TD) optical coherence tomography (OCT) findings in patients with solar
      retinopathy. Complete ocular examinations and OCT were performed in two patients
      presenting with acute solar retinopathy soon after observation of an eclipse.
      Both patients were evaluated with SD-OCT and TD-OCT at the same time. SD-OCT
      demonstrated characteristic defects at the level of the inner and outer segment
      junction of the photoreceptors in all the affected eyes and decreased
      reflectiveness of the retinal pigment epithelium layer. TD-OCT images showed
      unremarkable findings in two eyes with deteriorated visual acuity. SD-OCT
      improves diagnosis and assessment of the degree and nature of foveal damage in
      patients with solar retinopathy and may be an important tool for use in
      identifying foveal damage not detected by TD-OCT. SD-OCT may be preferable to TD
      OCT for confirmation or assessment of the degree of foveal damage in patients
      with solar retinopathy.

PMID- 21860578
TI  - Intravitreal bevacizumab (avastin) as an adjuvant for the treatment of posterior
      scleritis.
AB  - We report a case of posterior scleritis effectively managed with intravitreal
      bevacizumab. A 71-year-old woman was diagnosed with posterior scleritis. Although
      she was initially treated with systemic steroids, her clinical presentation
      deteriorated. She was then treated with a single intravitreal injection of
      bevacizumab and aqueous humor collection. The aqueous level of vascular
      endothelial growth factor prior to the intravitreal injection was 880.51 pg/mL,
      greater than that in the healthy control group (p < 0.001). One month later, the
      scleritis was completely resolved, and the patient remained stable during six
      months of follow-up. Intravitreal bevacizumab appears to be an effective adjuvant
      therapy for patients with posterior scleritis.

PMID- 21860580
TI  - A case of pediatric idiopathic intracranial hypertension presenting with
      divergence insufficiency.
AB  - An 11-year-old female presenting diplopia only at distance was found to have
      comitant esotropia of 20 prism diopters (PD) at distance and normal alignment at
      nearer proximity. Other ocular movement, including abduction, was normal and a
      thorough neurologic examination was also normal. The deviation angle of esotropia
      was increased to 35 PD in 6 months, and a brain magnetic resonance imaging with
      venogram at that time demonstrated no intracranial lesion. A lumbar puncture
      showed increased opening pressure but the cerebrospinal fluid composition was
      normal. The patient was diagnosed as having idiopathic intracranial hypertension
      and treated with oral acetazolamide. Three months after treatment, the deviation
      angle decreased to 10 PD. This is a case report of divergence insufficiency in
      pediatric idiopathic intracranial hypertension, with an increasing deviation
      angle of esotropia. Although sixth cranial nerve palsy is a common neurologic
      manifestation in intracranial hypertension, clinicians should be aware of the
      possibility of divergence insufficiency. Also, ophthalmoparesis may not be
      apparent and typical at first presentation, as seen in this case, and therefore
      ophthalmologists should be aware of this fact, while conducting careful and
      proper evaluation, follow-up, and intervention.

PMID- 21860579
TI  - Late-onset Citrobacter koseri endophthalmitis with suture exposure after
      secondary intraocular lens implantation.
AB  - A 54-year-old male patient was seen in clinic for ocular pain and decreased
      vision in the right eye with duration of two days. He underwent a cataract
      operation for his right eye 12 years ago, then a sclera-fixated secondary
      intraocular implantation and pars plana vitrectomy three years ago due to
      intraocular lens dislocation. At the initial visit, his visual acuity was
      restricted to the perception of hand motion. An edematous cornea, cells, flare
      with hypopyon, and exposed suture material at were observed at the six o'clock
      direction by slit lamp. Vitreous opacity was noted from B-scan ultrasonography.
      The patient was diagnosed with late-onset endophthalmitis and an intravitreal
      cocktail injection was done. On the next day, the hypopyon was aggravated, and
      therefore a pars plana vitrectomy was performed. A vitreous culture tested
      positive for Citrobacter koseri. After 12 weeks, the best corrected visual acuity
      of the right eye improved to 0.7 and a fundus examination revealed a relatively
      normal optic disc and retinal vasculature. We herein report the first case of
      endophthalmitis caused by Citrobacter koseri in Korea. Exposed suture material
      was suspected as the source of infection in this case and prompt surgical
      intervention resulted in a relatively good visual outcome.

PMID- 21860581
TI  - A congruous superior quadrantanopsia following a junctional scotoma induced by
      asperogillosis.
AB  - A 69-year old man presented to us with decreased vision in his right eye and a
      relative afferent pupillary defect. Under the presumption that he was suffering
      from retrobulbar optic neuritis or ischemic optic neuropathy, visual field tests
      were performed, revealing the presence of a junctional scotoma. Imaging studies
      revealed tumorous lesions extending from the sphenoid sinus at the right superior
      orbital fissure, with erosion of the right medial orbital wall and optic canal.
      Right optic nerve decompression was performed via an endoscopic sphenoidectomy,
      and histopathologic examination confirmed the presence of aspergillosis. The
      patient did not receive any postoperative antifungal treatment; however, his
      vision improved to 20 / 40, and his visual field developed a left congruous
      superior quadrantanopsia 18 months postoperatively. A junctional scotoma can be
      caused by aspergillosis, demonstrating the importance of examining the
      asymptomatic eye when a patient is experiencing a loss of vision in one eye.
      Furthermore, damage to the distal optic nerve adjacent to the proximal optic
      chiasm can induce unusual congruous superior quadrantanopsia.

PMID- 21860582
TI  - Alcohol Use and Popularity: Social Payoffs from Conforming to Peers' Behavior.
AB  - Although many economic analyses of adolescents have examined the costs of risky
      behaviors, few have investigated the gains that young people derive from such
      actions, particularly in terms of social payoffs for complying with peer
      behavior. This paper studies the relationship between adolescents' use of alcohol
      (relative to that of their peers) and popularity at school. We use data from the
      National Longitudinal Study of Adolescent Health, a rich and nationally
      representative survey with detailed information on social networks. Our findings
      suggest that adolescents are socially rewarded for conforming to their peers'
      alcohol use and penalized (to a lesser degree) for increasing their consumption
      above that of their peers. Male adolescents are rewarded for keeping up with
      their peers' drinking and for getting drunk. Female adolescents are rewarded for
      drinking per se, but not necessarily for keeping up with their peers. The results
      offer new information on peer influence and have implications for substance abuse
      interventions at school and in the community.

PMID- 21860583
TI  - Thirty Year Trends in U.S. Adolescents' Civic Engagement: A Story of Changing
      Participation and Educational Differences.
AB  - Using annual cross-sectional data from Monitoring the Future, the present study
      examined trends in high school seniors' current and anticipated civic
      participation and beliefs over a 30-year period. We examined overall trends and
      patterns based on youths' post-high school educational plans. Findings point to
      declines in recent cohorts' involvement in conventional and alternative forms of
      engagement but greater involvement in community service. Regardless of period,
      the majority of youth said they intended to vote when eligible but few expressed
      trust in the government or elected officials. All civic indicators showed
      significant differences based on youths' college aspirations: Youth who planned
      to graduate from a 4-year college were more civically inclined than their peers
      with 2-year or no college plans.

PMID- 21860584
TI  - Qualities of Peer Relations on Social Networking Websites: Predictions from
      Negative Mother-Teen Interactions.
AB  - This study examined associations between characteristics of teenagers'
      relationships with their mothers and their later socializing behavior and peer
      relationship quality online. At age 13, teenagers and their mothers participated
      in an interaction in which mothers' and adolescents' behavior undermining
      autonomy and relatedness was observed, and indicators of teens' depressive
      symptoms and social anxiety were assessed. At age 20, youth self-reported on
      their online behaviors, youths' social networking webpages were observationally
      coded to assess peer relationship quality online, and symptoms of depression and
      social anxiety were reassessed. Results suggested that problematic mother-teen
      relationships were predictive of youths' later preference for online
      communication and greater likelihood of forming a friendship with someone met
      online, yet poorer quality in online relationships. Findings are discussed within
      a developmental framework suggesting the importance of considering youths' family
      interactions during early adolescence as predictors of future online socializing
      behavior and online interactions with peers.

PMID- 21860585
TI  - The History and Timing of Depression Onset as Predictors of Young-Adult Self
      Esteem.
AB  - Depression often emerges early in the lifecourse and is consistently shown to be
      associated with poor self-esteem. The three main objectives of the current study
      are to (1) evaluate the association between a history major depression and self
      esteem in young adulthood; (2) assess the relationship between timing of
      depression onset and young adult self-esteem; and (3) help rule out the
      alternative interpretation that the relationship between major depression and
      self-esteem is due to state dependence bias stemming from recent depressive
      symptoms and stressful life events. To address these objectives we use data from
      a two-wave panel study based on a community sample of young adults in Miami-Dade
      County, Florida (n = 1,197). Results indicated a history of major depression
      during sensitive periods of social development is associated with negative
      changes in self-esteem over a two-year period during the transition to young
      adulthood. Among those with a history of depression, earlier onset was more
      problematic than later onset for young adult self-esteem, although the difference
      disappeared once the level of self-esteem two years prior was controlled. The
      linkages between the history and timing of depression onset with self-esteem were
      observed net of recent depressive symptoms and stressful life events, and thus
      robust to an alternative interpretation of state dependence. The findings support
      the argument that major depression, especially if it develops earlier during
      child-adolescent development, has negative consequences for one's self-esteem.

PMID- 21860586
TI  - Involvement of activating NK cell receptors and their modulation in pathogen
      immunity.
AB  - Natural Killer (NK) cells are endowed with cell-structure-sensing receptors
      providing inhibitory protection from self-destruction (inhibitory NK receptors,
      iNKRs, including killer inhibitory receptors and other molecules) and rapid
      triggering potential leading to functional cell activation by Toll-like receptors
      (TLRs), cytokine receptors, and activating NK cell receptors including natural
      cytotoxicity receptors (NCRs, i.e., NKp46, NKp46, and NKp44). NCR and NKG2D
      recognize ligands on infected cells which may be endogenous or may directly bind
      to some structures derived from invading pathogens. In this paper, we address the
      known direct or indirect interactions between activating receptors and pathogens
      and their expression during chronic HIV and HCV infections.

PMID- 21860588
TI  - Biocompatibility evaluation of a new hydrogel dressing based on
      polyvinylpyrrolidone/polyethylene glycol.
AB  - The composition of the dressings is based on polyvinylpyrrolidone (PVP),
      polyethylene glycol (PEG), and agar. The electron beam irradiation technique has
      been used to prepare hydrogel wound dressings. The in vitro biocompatibility of
      the hydrogel was investigated by check samples (hydrocolloid Comfeel),
      antibacterial test (Staphylococcus aureus, Staphylococcus epidermidis,
      Pseudomonas aeruginosa, Escherichia Coli k12), anti fungal test (Candida
      Albicans) and cytotoxicity test (Fibroblast L929). Results have shown cell
      attachment characteristics and nontoxicity of all samples. Antibacterial testing
      also showed that the antibacterial effect of the hydrogel sample to the check
      sample increased to 30%. Also, investigation of antifungal analysis did not show
      any trace of fungi growth on the surface of the hydrogel, whereas antifungal
      effect did not observe on the surface of the check sample. Finally, this hydrogel
      sample showed a good in vitro biocompatibility.

PMID- 21860587
TI  - Protein profiling of human nonpigmented ciliary epithelium cell secretome: the
      differentiation factors characterization for retinal ganglion cell line.
AB  - The purpose of this paper was to characterize proteins secreted from the human
      nonpigmented ciliary epithelial (HNPE) cells, which have differentiated a rat
      retinal ganglion cell line, RGC-5. Undifferentiated RGC-5 cells have been shown
      to express several marker proteins characteristic of retinal ganglion cells.
      However, RGC-5 cells do not respond to N-methyl-D aspartate (NMDA), or glutamate.
      HNPE cells have been shown to secrete numbers of neuropeptides or neuroproteins
      also found in the aqueous humor, many of which have the ability to influence the
      activity of neuronal cells. This paper details the profile of HNPE cell-secreted
      proteins by proteomic approaches. The experimental results revealed the
      identification of 132 unique proteins from the HNPE cell-conditioned SF-medium.
      The biological functions of a portion of these identified proteins are involved
      in cell differentiation. We hypothesized that a differentiation system of HNPE
      cell-conditioned SF-medium with RGC-5 cells can induce a differentiated phenotype
      in RGC-5 cells, with functional characteristics that more closely resemble
      primary cultures of rat retinal ganglion cells. These proteins may replace harsh
      chemicals, which are currently used to induce cell differentiation.

PMID- 21860589
TI  - Arginase Inhibition by Ethylacetate Extract of Caesalpinia sappan Lignum
      Contributes to Activation of Endothelial Nitric Oxide Synthase.
AB  - Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood
      circulation and removing stasis. During a screening procedure on medicinal
      plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed
      inhibitory activity on arginase which has recently been reported as a novel
      therapeutic target for the treatment of cardiovascular diseases such as
      atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate
      in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE
      reciprocally increased NOx production through enhancement of eNOS dimer stability
      without any significant changes in the protein levels of eNOS and arginase II
      expression. Furthermore, CLE-dependent arginase inhibition resulted in increase
      of NO generation and decrease of superoxide production on endothelium of isolated
      mice aorta. These results indicate that CLE augments NO production on endothelium
      through inhibition of arginase activity, and may imply their usefulness for the
      treatment of cardiovascular diseases associated with endothelial dysfunction.

PMID- 21860590
TI  - 5-hydroxytryptamine generates tonic inward currents on pacemaker activity of
      interstitial cells of cajal from mouse small intestine.
AB  - In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an
      effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the
      mouse small intestine. The actions of 5-HT on pacemaker activities were
      investigated using a whole-cell patch-clamp technique, intracellular Ca(2+)
      ([Ca(2+)](i)) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic
      inward currents on pacemaker currents in ICC under the voltage-clamp mode in a
      dose-dependent manner. Based on RT-PCR results, we found the existence of 5
      HT(2B, 3, 4, and 7) receptors in ICC. However, SDZ 205557 (a 5-HT(4) receptor
      antagonist), SB 269970 (a 5-HT7 receptor antagonist), 3-tropanylindole - 3 -
      carboxylate methiodide (3-TCM; a 5-HT(3) antagonist) blocked the 5-HT-induced
      action on pacemaker activity, but not SB 204741 (a 5-HT(2B) receptor antagonist).
      Based on [Ca(2+)](i) analysis, we found that 5-HT increased the intensity of
      [Ca(2+)](i). The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT
      induced action on pacemaker activity of ICC, but not SB 203580. In summary, these
      results suggest that 5-HT can modulate pacemaker activity through 5-HT(3, 4, and
      7) receptors via [Ca(2+)](i) mobilization and regulation of mitogen-activated
      protein kinases.

PMID- 21860591
TI  - Influence of exposure to extremely low frequency magnetic field on neuroendocrine
      cells and hormones in stomach of rats.
AB  - Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a
      variety of behavioral and physiological changes in animals. The stomach, as the
      most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is
      crucial for the initiation of a full stress response against all harmful stress.
      Thus, the purpose of this study was to examine whether ELF-MF stimuli induce
      changes in the activity of neuroendocrine cells, considering their involvement in
      endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF
      (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered
      the distribution and occurrence of gastrin, ghrelin and somatostatin-positive
      endocrine cells in the stomach of rats. The change, however, in the secretion of
      those hormones into blood from endocrine cells did not appear significantly with
      ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week
      induced an increase in BaSO(4) suspension propelling ratio of gastrointestinal
      tract, indicating that ELF-MF affects gastrointestinal motility. Our study
      revealed that ELF-MF exposure might influence the activity of endocrine cells, an
      important element of the intrinsic regulatory system in the digestive tract. The
      pathophysiological character of these changes and the mechanism responsible for
      neuroendocrine cell are still unclear and require further studies.

PMID- 21860592
TI  - The Relaxing Effect of alpha-Defensin 1 on the Adrenergic Responses of Rat
      Bladder.
AB  - Defensins, cysteine-rich cationic polypeptides released from neutrophils, are
      known to have powerful antimicrobial properties. In this study, we sacrificed 30
      rats to investigate the effects of alpha-defensin 1 on detrusor muscle
      contractions in isolated rat bladder. From the experiments we found relaxing
      effects of alpha-defensin 1 on the contractions induced by phenylephrine (PE) but
      not by bethanechol (BCh) in the detrusor smooth muscles. To determine the
      mechanisms of the effects of alpha-defensin 1, the changes of effects on PE
      induced contraction by alpha-defensin 1 pretreatment were observed after
      pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor
      (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF
      kappaB inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The
      contractile responses of PE (10(-9)~10(-4) M) were significantly decreased in
      some concentrations of alpha-defensin 1 (5*10(-9) and 5*10(-8) M). When strips
      were pretreated with NF-kappaB inhibitors (PDTC and sulfasalazine; 10(-7)~10(-6)
      M), the relaxing responses by alpha-defensin 1 pretreatment were disappeared. The
      present study demonstrated that alpha-defensin 1 has relaxing effects on the
      contractions of rat detrusor muscles, through NF-kappaB pathway. Further studies
      in vivo are required to clarify whether alpha-defensin 1 might be clinically
      related with bladder dysfunction by inflammation process.

PMID- 21860593
TI  - GS28 Protects Neuronal Cell Death Induced by Hydrogen Peroxide under Glutathione
      Depleted Condition.
AB  - Golgi SNAP receptor complex 1 (GS28) has been implicated in vesicular transport
      between intra-Golgi networks and between endoplasmic reticulum (ER) and Golgi.
      Additional role(s) of GS28 within cells have not been well characterized. We
      observed decreased expression of GS28 in rat ischemic hippocampus. In this study,
      we examined the role of GS28 and its molecular mechanisms in neuronal (SK-N-SH)
      cell death induced by hydrogen peroxide (H(2)O(2)). GS28 siRNA-transfected cells
      treated with H(2)O(2) showed a significant increase in cytotoxicity under
      glutathione (GSH)-depleted conditions after pretreatment with buthionine
      sulfoximine, which corresponded to an increase of intracellular reactive oxygen
      species (ROS) in the cells. Pretreatment of GS28 siRNA-transfected cells with p38
      chemical inhibitor significantly inhibited cytotoxicity; we also observed that
      p38 was activated in the cells by immunoblot analysis. We confirmed the role of
      p38 MAPK in cotransfected cells with GS28 siRNA and p38 siRNA in the cell
      viability assay, flow cytometry, and immunoblot. Involvement of apoptotic or
      autophagic processes in the cells was not shown in the cell viability, flow
      cytometry, and immunoblot analyses. However, pretreatment of the cells with
      necrostatin-1 completely inhibited H(2)O(2)-induced cytotoxicity, ROS generation,
      and p38 activation, indicating that the cell death is necroptotic. Collectively
      these data imply that H(2)O(2) induces necroptotic cell death in the GS28 siRNA
      transfected cells and that the necroptotic signals are mediated by sequential
      activations in RIP1/p38/ROS. Taken together, these results indicate that GS28 has
      a protective role in H(2)O(2)-induced necroptosis via inhibition of p38 MAPK in
      GSH-depleted neuronal cells.

PMID- 21860594
TI  - Genipin Selectively Inhibits TNF-alpha-activated VCAM-1 But Not ICAM-1 Expression
      by Upregulation of PPAR-gamma in Human Endothelial Cells.
AB  - Vascular inflammation process has been suggested to be an important risk factor
      in the development of atherosclerosis. Recently we reported that induction of
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) selectively
      inhibits vascular cell adhesion molecule-1 (VCAM-1) but not intercellular cell
      adhesion molecule-1 (ICAM-1) in tumor necrosis factor (TNF)-alpha-activated human
      umbilical vein endothelial cells (HUVEC). In this study, we investigated whether
      genipin inhibits expression of cellular adhesion molecules, which is relevant to
      inflammation. Pretreatment with genipin reduced reactive oxygen species (ROS)
      production and expression of VCAM-1, but not ICAM-1 in TNF-alpha-activated HUVEC.
      Genipin dose- and time-dependently increased PPAR-gamma expression and inhibited
      TNF-alpha-induced phosphorylation of Akt and PKC with different degrees. Finally,
      genipin prevented TNF-alpha-induced adhesion of U937 monocytic cells to HUVEC.
      Taken together, these results indicate that upregualtion of PPAR-gamma by genipin
      selectively inhibits TNF-alpha-induced expression of VCAM-1, in which regulation
      of Akt and/or PKC play a key role. We concluded that genipin can be used for the
      treatment of cardiovascular disorders such as atherosclerosis.

PMID- 21860595
TI  - Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior
      Hypothalamic Area of GAD65-eGFP Mice.
AB  - Corticosterone is known to modulate GABAergic synaptic transmission in the
      hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms
      are largely unknown. In the anterior hypothalamic area (AHA), the
      sympathoinhibitory center that project GABAergic neurons onto the PVN, we
      examined the expression of glucocorticoid receptor (GR) and mineralocorticoid
      receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and
      the effects of corticosterone on the burst firing using adrenalectomized
      transgenic mice. GR or MR immunoreactivity was detected from the subpopulations
      of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR
      (42%), MR (38%) or both (8%). In addition, in brain slices incubated with
      corticosterone together with RU486 (MR-dominant group), the proportion of neurons
      showing a burst firing pattern was significantly higher than those in the slices
      incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR
      dominant group; 64 vs. 11~14%, p< 0.01 by chi(2)-test). Taken together, the
      results show that the corticosteroid receptors are expressed on the GABAergic
      neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the
      firing pattern of these neurons. This study newly provides the experimental
      evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA
      in the vicinity of the PVN.

PMID- 21860596
TI  - Myoplasmic [ca], crossbridge phosphorylation and latch in rabbit bladder smooth
      muscle.
AB  - TONIC SMOOTH MUSCLE EXHIBIT THE LATCH PHENOMENON: high force at low myosin
      regulatory light chains (MRLC) phosphorylation, shortening velocity (Vo), and
      energy consumption. However, the kinetics of MRLC phosphorylation and cellular
      activation in phasic smooth muscle are unknown. The present study was to
      determine whether Ca(2+)-stimulated MRLC phosphorylation could suffice to explain
      the agonist- or high K(+)-induced contraction in a fast, phasic smooth muscle. We
      measured myoplasmic [Ca(2+)], MRLC phosphorylation, half-time after step
      shortening (a measure of Vo) and contractile stress in rabbit urinary bladder
      strips. High K(+)-induced contractions were phasic at both 22C and 37C:
      myoplasmic [Ca(2+)], MRLC phosphorylation, 1/half-time, and contractile stress
      increased transiently and then all decreased to intermediate values. Carbachol
      (CCh)-induced contractions exhibited latch at 37C: stress was maintained at high
      levels despite decreasing myoplasmic [Ca(2+)], MRLC phosphorylation, and 1/half
      time. At 22C CCh induced sustained elevations in all parameters. 1/half-time
      depended on both myoplasmic [Ca(2+)] and MRLC phosphorylation. The steady-state
      dependence of stress on MRLC phosphorylation was very steep at 37C in the CCh- or
      K(+)-depolarized tissue and reduced temperature flattend the dependence of stress
      on MRLC phosphorylation compared to 37C. These data suggest that phasic smooth
      muscle also exhibits latch behavior and latch is less prominent at lower
      temperature.

PMID- 21860597
TI  - CD40 Co-stimulation Inhibits Sustained BCR-induced Ca Signaling in Response to
      Long-term Antigenic Stimulation of Immature B Cells.
AB  - Regulation of B cell receptor (BCR)-induced Ca(2+) signaling by CD40 co
      stimulation was compared in long-term BCR-stimulated immature (WEHI-231) and
      mature (Bal-17) B cells. In response to long-term pre-stimulation of immature
      WEHI-231 cells to alpha-IgM antibody (0.5~48 hr), the initial transient decrease
      in BCR-induced [Ca(2+)](i) was followed by spontaneous recovery to control level
      within 24 hr. The recovery of Ca(2+) signaling in WEHI-231 cells was not due to
      restoration of internalized receptor but instead to an increase in the levels of
      PLCgamma2 and IP(3)R-3. CD40 co-stimulation of WEHI-231 cells prevented BCR
      induced cell cycle arrest and apoptosis, and it strongly inhibited the recovery
      of BCR-induced Ca(2+) signaling. CD40 co-stimulation also enhanced BCR
      internalization and reduced expression of PLCgamma2 and IP(3)R-3. Pre-treatment
      of WEHI-231 cells with the antioxidant N-acetyl-L-cysteine (NAC) strongly
      inhibited CD40-mediated prevention of the recovery of Ca(2+) signaling. In
      contrast to immature WEHI-231 cells, identical long-term alpha-IgM pre
      stimulation of mature Bal-17 cells abolished the increase in BCR-induced
      [Ca(2+)](i), regardless of CD40 co-stimulation. These results suggest that CD40
      mediated signaling prevents antigen-induced cell cycle arrest and apoptosis of
      immature B cells through inhibition of sustained BCR-induced Ca(2+) signaling.

PMID- 21860599
TI  - Analysis of Diacylglycerol Molecular Species in Cellular Lipid Extracts by Normal
      Phase LC-Electrospray Mass Spectrometry.
AB  - The quantitative determination of 48 molecular species of regioisomeric
      diacylglycerols has been made in a single analysis of an extract of bone marrow
      derived macrophages. The analytical procedure involves solvent extraction of
      neutral lipids, including diacylglycerols, derivatization of free hydroxyl
      moieties as 2,4-difluorophenyl urethane, and analysis by normal phase liquid
      chromatography-tandem mass spectrometry. The derivatization step not only
      prevents fatty acyl group migration, thus allowing determination of both 1,2- and
      1,3-diacylglycerols, but also yields species that are sensitively and uniquely
      determined by constant neutral loss mass spectrometry. The method also detected
      monoacylglycerols, which were characterized by unique retention time and
      collisional spectra, and were present in mouse bone marrow derived macrophage
      extracts.

PMID- 21860598
TI  - Multiscale Adaptive Regression Models for Neuroimaging Data.
AB  - Neuroimaging studies aim to analyze imaging data with complex spatial patterns in
      a large number of locations (called voxels) on a two-dimensional (2D) surface or
      in a 3D volume. Conventional analyses of imaging data include two sequential
      steps: spatially smoothing imaging data and then independently fitting a
      statistical model at each voxel. However, conventional analyses suffer from the
      same amount of smoothing throughout the whole image, the arbitrary choice of
      smoothing extent, and low statistical power in detecting spatial patterns. We
      propose a multiscale adaptive regression model (MARM) to integrate the
      propagation-separation (PS) approach (Polzehl and Spokoiny, 2000, 2006) with
      statistical modeling at each voxel for spatial and adaptive analysis of
      neuroimaging data from multiple subjects. MARM has three features: being spatial,
      being hierarchical, and being adaptive. We use a multiscale adaptive estimation
      and testing procedure (MAET) to utilize imaging observations from the neighboring
      voxels of the current voxel to adaptively calculate parameter estimates and test
      statistics. Theoretically, we establish consistency and asymptotic normality of
      the adaptive parameter estimates and the asymptotic distribution of the adaptive
      test statistics. Our simulation studies and real data analysis confirm that MARM
      significantly outperforms conventional analyses of imaging data.

PMID- 21860600
TI  - Electrospray ionization Fourier transform mass spectrometric analysis of intact
      bikunin glycosaminoglycan from normal human plasma.
AB  - A mixture of glycosaminoglycan (GAG) chains from a plasma proteoglycan bikunin
      was fractionated using native, continuous-elution polyacrylamide gel
      electrophoresis, and the resulting fractions were analyzed by electrospray
      ionization Fourier transform mass spectrometry (ESI FTMS). Molecular mass
      analysis of the intact GAG afforded information about the length and composition
      of GAG chains in the mixture. Ambiguity in the interpretation of the intact GAG
      mass spectra was eliminated by conducting an additional experiment in which the
      GAG chains of known molecular mass were treated with a GAG-degrading enzyme,
      chondroitinase ABC, and the digestion products were analyzed by ESI FTMS. The
      plasma bikunin GAG chains consisted predominantly of odd number of saccharides,
      although few chains consisting of even number of saccharides were also detected.
      Majority of the analyzed chains were tetrasulfated or pentasulfated and comprised
      by 29 to 41 monosaccharides.

PMID- 21860601
TI  - Multistage Tandem Mass Spectrometry of Chondroitin Sulfate and Dermatan Sulfate.
AB  - Chondroitin/dermatan sulfate (CS/DS) is a glycosaminoglycan (GAG) found in
      abundance in extracellular matrices. In connective tissue, CS/DS proteoglycans
      play structural roles in maintaining viscoelasticity through the large number of
      immobilized sulfate groups on CS/DS chains. CS/DS chains also bind protein
      families including growth factors and growth factor receptors. Through such
      interactions, CS/DS chains play important roles in neurobiochemical processes,
      connective tissue homeostasis, coagulation, and cell growth regulation.
      Expression of DS has been observed to increase in cancerous tissue relative to
      controls. In earlier studies, MS(2) was used to compare the types of CS/DS
      isomers present in biological samples. The results demonstrated that product ion
      abundances reflect the types of CS/DS repeats present and can be used
      quantitatively. It was not clear, however, to which of the CS/DS repeats the
      product ions abundances were sensitive. The present work explores the utility of
      MS(3) for structural characterization of CS/DS oligosaccharides. The data show
      that MS(3) product ion abundances correlate with the presence of DS-like repeats
      in specific positions on the oligosaccharide chains.

PMID- 21860602
TI  - Rapid Profiling of Bovine and Human Milk Gangliosides by Matrix-Assisted Laser
      Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass
      Spectrometry.
AB  - Gangliosides are anionic glycosphingolipids widely distributed in vertebrate
      tissues and fluids. Their structural and quantitative expression patterns depend
      on phylogeny and are distinct down to the species level. In milk, gangliosides
      are exclusively associated with the milk fat globule membrane. They may
      participate in diverse biological processes but more specifically to host
      pathogen interactions. However, due to the molecular complexities, the analysis
      needs extensive sample preparation, chromatographic separation, and even chemical
      reaction, which makes the process very complex and time-consuming. Here, we
      describe a rapid profiling method for bovine and human milk gangliosides
      employing matrix-assisted desorption/ionization (MALDI) Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometry (MS). Prior to the analyses of
      biological samples, milk ganglioside standards GM3 and GD3 fractions were first
      analyzed in order to validate this method. High mass accuracy and high resolution
      obtained from MALDI FTICR MS allow for the confident assignment of chain length
      and degree of unsaturation of the ceramide. For the structural elucidation,
      tandem mass spectrometry (MS/MS), specifically as collision-induced dissociation
      (CID) and infrared multiphoton dissociation (IRMPD) were employed. Complex
      ganglioside mixtures from bovine and human milk were further analyzed with this
      method. The samples were prepared by two consecutive chloroform/methanol
      extraction and solid phase extraction. We observed a number of differences
      between bovine milk and human milk. The common gangliosides in bovine and human
      milk are NeuAc-NeuAc-Hex-Hex-Cer (GD3) and NeuAc-Hex-Hex-Cer (GM3); whereas, the
      ion intensities of ganglioside species are different between two milk samples.
      Kendrick mass defect plot yields grouping of ganglioside peaks according to their
      structural similarities. Gangliosides were further probed by tandem MS to confirm
      the compositional and structural assignments. We found that only in human milk
      gangliosides was the ceramide carbon always even numbered, which is consistent
      with the notion that differences in the oligosaccharide and the ceramide moieties
      confer to their physiological distinctions.

PMID- 21860603
TI  - Methods development for Analysis of Partially Deglycosylated Proteins and
      Application to an HIV Envelope Protein Vaccine Candidate.
AB  - The work presented herein describes the first comprehensive analysis of a
      partially deglycosylated HIV vaccine candidate envelope protein (Env). The Env,
      JRFL gp140 DeltaCF, with 27 potential glycosylation sites, was partially
      deglycosylated with PNGase F as part of a strategy to generate a more immunogenic
      HIV vaccine, and the resulting protein's glycosylation was characterized in a
      unique workflow using two different glycosidases, Endo H and Endo F3. This unique
      analysis protocol provided for coverage on 26 of the 27 glycosylation sites, and
      the data showed that the biochemical treatment with PNGase F resulted in a highly
      heterogeneous glycoprotein product that had been partially deglycosylated at most
      of the glycosylation sites. The protocols described in this work could be useful
      for characterizing the glycosylation site occupancy of other native or
      biochemically deglycosylated proteins.

PMID- 21860604
TI  - The roles and evolutionary patterns of intronless genes in deuterostomes.
AB  - Genes without introns are a characteristic feature of prokaryotes, but there are
      still a number of intronless genes in eukaryotes. To study these eukaryotic genes
      that have prokaryotic architecture could help to understand the evolutionary
      patterns of related genes and genomes. Our analyses revealed a number of
      intronless genes that reside in 6 deuterostomes (sea urchin, sea squirt,
      zebrafish, chicken, platypus, and human). We also determined the conservation for
      each intronless gene in archaea, bacteria, fungi, plants, metazoans, and other
      eukaryotes. Proportions of intronless genes that are inherited from the common
      ancestor of archaea, bacteria, and eukaryotes in these species were consistent
      with their phylogenetic positions, with more proportions of ancient intronless
      genes residing in more primitive species. In these species, intronless genes
      belong to different cellular roles and gene ontology (GO) categories, and some of
      these functions are very basic. Part of intronless genes is derived from other
      intronless genes or multiexon genes in each species. In conclusion, we showed
      that a varying number and proportion of intronless genes reside in these 6
      deuterostomes, and some of them function importantly. These genes are good
      candidates for subsequent functional and evolutionary analyses specifically.

PMID- 21860605
TI  - Cross-Genome Comparisons of Newly Identified Domains in Mycoplasma gallisepticum
      and Domain Architectures with Other Mycoplasma species.
AB  - Accurate functional annotation of protein sequences is hampered by important
      factors such as the failure of sequence search methods to identify relationships
      and the inherent diversity in function of proteins related at low sequence
      similarities. Earlier, we had employed intermediate sequence search approach to
      establish new domain relationships in the unassigned regions of gene products at
      the whole genome level by taking Mycoplasma gallisepticum as a specific example
      and established new domain relationships. In this paper, we report a detailed
      comparison of the conservation status of the domain and domain architectures of
      the gene products that bear our newly predicted domains amongst 14 other
      Mycoplasma genomes and reported the probable implications for the organisms. Some
      of the domain associations, observed in Mycoplasma that afflict humans and other
      non-human primates, are involved in regulation of solute transport and DNA
      binding suggesting specific modes of host-pathogen interactions.

PMID- 21860606
TI  - Assessing the Application of a Geographic Presence-Only Model for Land
      Suitability Mapping.
AB  - Recent advances in ecological modeling have focused on novel methods for
      characterizing the environment that use presence-only data and machine-learning
      algorithms to predict the likelihood of species occurrence. These novel methods
      may have great potential for land suitability applications in the developing
      world where detailed land cover information is often unavailable or incomplete.
      This paper assesses the adaptation and application of the presence-only
      geographic species distribution model, MaxEnt, for agricultural crop suitability
      mapping in a rural Thailand where lowland paddy rice and upland field crops
      predominant. To assess this modeling approach, three independent crop presence
      datasets were used including a social-demographic survey of farm households, a
      remote sensing classification of land use/land cover, and ground control points,
      used for geodetic and thematic reference that vary in their geographic
      distribution and sample size. Disparate environmental data were integrated to
      characterize environmental settings across Nang Rong District, a region of
      approximately 1,300 sq. km in size. Results indicate that the MaxEnt model is
      capable of modeling crop suitability for upland and lowland crops, including rice
      varieties, although model results varied between datasets due to the high
      sensitivity of the model to the distribution of observed crop locations in
      geographic and environmental space. Accuracy assessments indicate that model
      outcomes were influenced by the sample size and the distribution of sample points
      in geographic and environmental space. The need for further research into
      accuracy assessments of presence-only models lacking true absence data is
      discussed. We conclude that the Maxent model can provide good estimates of crop
      suitability, but many areas need to be carefully scrutinized including geographic
      distribution of input data and assessment methods to ensure realistic modeling
      results.

PMID- 21860608
TI  - Ribosomal Protein L19 and L22 Modulate TLR3 Signaling.
AB  - BACKGROUND: Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA)
      and induces inflammation. In this study we attempted to ascertain if there are
      endogenous host molecules controlling the production of cytokines and chemokines.
      Two candidates, ribosomal protein L19 and L22, were analyzed to determine if they
      influence cytokine production followed by TLR3 activation. In this study we
      report that L19 acts upon production of IP-10 or IL-8 differently in glioblastoma
      cells. METHODS: L19 or L22 was transfected into HEK293-TLR3, A549 or A172 cells.
      After treatment with several inhibitors of NF-kB, PI3K, p38 or ERK, production of
      IL-8 or IP-10 was measured by ELISA. siRNA was introduced to suppress expression
      of L19. After Vesicular stomatitis virus infection, viral multiplication was
      measured by western blot. RESULTS: L19 increased ERK activation to produce IL-8.
      In A172 cells, in which TLR3 is expressed at endosomes, L19 inhibited interferon
      regulatory factor 3 (IRF3) activation and IP-10 production to facilitate viral
      multiplication, whereas L19 inhibited viral multiplication in A549 cells bearing
      TLR3 on their cell membrane. CONCLUSION: Our results suggest that L19 regulates
      TLR3 signaling, which is cell type specific and may be involved in pathogenesis
      of autoimmune diseases and chronic inflammatory diseases.

PMID- 21860609
TI  - Formulation and Characterization of Antigen-loaded PLGA Nanoparticles for
      Efficient Cross-priming of the Antigen.
AB  - BACKGROUND: Nanoparticles (NPs) prepared from biodegradable polymers, such as
      poly (D,L-lactic acid-co-glycolic acid) (PLGA), have been studied as vehicles for
      the delivery of antigens to phagocytes. This paper describes the preparation of
      antigen-loaded PLGA-NPs for efficient cross-priming. METHODS: NPs containing a
      similar amount of ovalbumin (OVA) but different sizes were produced using a
      micromixer-based W/O/W solvent evaporation procedure, and the efficiency of the
      NPs to induce the cross-presentation of OVA peptides were examined in dendritic
      cells (DCs). Cellular uptake and biodistribution studies were performed using
      fluorescein isothiocyanate (FITC)-loaded NPs in mice. RESULTS: The NPs in the
      range of 1.1~1.4um in size were the most and almost equally efficient in inducing
      the cross-presentation of OVA peptides via H-2K(b) molecules. Cellular uptake and
      biodistribution studies showed that opsonization of the NPs with mouse IgG
      greatly increased the percentage of FITC-positive cells in the spleen and lymph
      nodes. The major cell type of FITC-positive cells in the spleen was macrophages,
      whereas that of lymph nodes was DCs. CONCLUSION: These results show that IgG
      opsonized PLGA-NPs with a mean size of 1.1um would be the choice of biodegradable
      carriers for the targeted-delivery of protein antigens for cross-priming in vivo.

PMID- 21860607
TI  - MicroRNAs in Human Diseases: From Cancer to Cardiovascular Disease.
AB  - The great discovery of microRNAs (miRNAs) has revolutionized current cell biology
      and medical science. miRNAs are small conserved non-coding RNA molecules that
      post-transcriptionally regulate gene expression by targeting the 3' untranslated
      region of specific messenger RNAs for degradation or translational repression.
      New members of the miRNA family are being discovered on a daily basis and
      emerging evidence has demonstrated that miRNAs play a major role in a wide range
      of developmental process including cell proliferation, cell cycle, cell
      differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate,
      neuronal gene expression, brain morphogenesis, muscle differentiation and stem
      cell division. Moreover, a large number of studies have reported links between
      alterations of miRNA homeostasis and pathological conditions such as cancer,
      psychiatric and neurological diseases, cardiovascular disease, and autoimmune
      disease. Interestingly, in addition, miRNA deficiencies or excesses have been
      correlated with a number of clinically important diseases ranging from cancer to
      myocardial infarction. miRNAs can repress the gene translation of hundreds of
      their targets and are therefore well-positioned to target a multitude of cellular
      mechanisms. As a consequence of extensive participation in normal functions, it
      is quite logical to ask the question if abnormalities in miRNAs should have
      importance in human diseases. Great discoveries and rapid progress in the past
      few years on miRNAs provide the hope that miRNAs will in the near future have a
      great potential in the diagnosis and treatment of many diseases. Currently, an
      explosive literature has focussed on the role of miRNA in human cancer and
      cardiovascular disease. In this review, I briefly summarize the explosive current
      studies about involvement of miRNA in various human cancers and cardiovascular
      disease.

PMID- 21860610
TI  - Enhancement of Allergen-induced Airway Inflammation by NOX2 Deficiency.
AB  - BACKGROUND: NADPH oxidase (NOX) modulates cell proliferation, differentiation and
      immune response through generation of reactive oxygen species. Particularly, NOX2
      is recently reported to be important for regulating Treg cell differentiation of
      CD4+ T cells. METHODS: We employed ovalbumin-induced airway inflammation in wild
      type and NOX2-deficient mice and analyzed tissue histopathology and cytokine
      profiles. RESULTS: We investigated whether NOX2-deficiency affects T cell
      mediated airway inflammation. Ovalbumin injection which activates T cell-mediated
      allergic response increased airway inflammation in wild-type mice, as evidenced
      by increased immune cell infiltration, allergic cytokine expression, and goblet
      cell hyperplasia in the lung. Interestingly, NOX2 knockout (KO) mice were more
      susceptible to allergen-induced lung inflammation compared to wild-type mice.
      Immune cells including neutrophils, lymphocytes, macrophages, and eosinophils
      were drastically infiltrated into the lung of NOX2 KO mice and mucus secretion
      was substantially increased in deficiency of NOX2. Furthermore, inflammatory
      allergic cytokines and eotaxin were significantly elevated in NOX2 KO mice, in
      accordance with enhanced generation of inflammatory cytokines interleukin-17 and
      interferon-gamma by CD4+ T cells. CONCLUSION: These results indicate that NOX2
      deficiency favorably produces inflammatory cytokines by T cells and thus
      increases the susceptibility to severe airway inflammation.

PMID- 21860611
TI  - Identification of CM1 as a Pathogenic Factor in Inflammatory Diseases and Cancer.
AB  - BACKGROUND: CM1 (centrocyte/-blast marker 1) was defined by a mAb against
      concanavalin A (Con A) activated PBMC. It is expressed in germinal center of
      human tonsil and on the surface of activated PBMC as well as cancer cells.
      Recently, increased productions of pro-inflammatory mediators were detected from
      activated PBMC by CM1 ligation. METHODS: However, there is a limitation to
      explain the exact role of CM1 on inflammation and its related mechanisms, since
      the identity of CM1 is still not clarified. In our previous study, we have
      already confirmed that soluble form of CM1 was produced by Raji. Therefore, we
      performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture
      supernatant using anti-CM1 mAbs. RESULTS: As a result, we found that CM1 is
      identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results
      by silencing ENO1 using siRNA. It was also confirmed through competition assay
      between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role
      of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells
      with anti-CM1 mAbs induces the extensive production of prostaglandin
      E(2)(PGE(2)). In addition, the increased activity of matrix metalloproteinase
      (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation.
      CONCLUSION: CM1 is identical to ENO1 and it might be an important role in the
      regulation of inflammatory responses.

PMID- 21860612
TI  - Enhanced Induction of T Cell Immunity Using Dendritic Cells Pulsed with HIV Tat
      and HCMV-pp65 Fusion Protein In Vitro.
AB  - BACKGROUND: Cytotoxic T lymphocytes (CTLs) appear to play an important role in
      the control and prevention of human cytomegalovirus (HCMV) infection. The pp65
      antigen is a structural protein, which has been defined as a potential target for
      effective immunity against HCMV infection. Incorporation of an 11 amino acid
      region of the HIV TAT protein transduction domain (Tat) into protein facilitates
      rapid, efficient entry into cells. METHODS: To establish a strategy for the
      generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C
      terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with
      Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear
      cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65
      N&C protein and immune responses induced was examined using IFN-gamma ELISPOT
      assay, cytotoxicity assay and tetramer staining. RESULTS: DCs pulsed with
      Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with
      pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of
      CD8(+) and CD4(+) T-cell responses. The T cells induced by DCs pulsed with
      Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against
      autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen.
      CONCLUSION: Our results suggest that DCs pulsed with Tat/pp65 N&C protein
      effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein
      may be useful for the development of adoptive T-cell immunotherapy and DC-based
      vaccines.

PMID- 21860613
TI  - Heterogeneous computing for vertebra detection and segmentation in x-ray images.
AB  - The context of this work is related to the vertebra segmentation. The method we
      propose is based on the active shape model (ASM). An original approach taking
      advantage of the edge polygonal approximation was developed to locate the
      vertebra positions in a X-ray image. Despite the fact that segmentation results
      show good efficiency, the time is a key variable that has always to be optimized
      in a medical context. Therefore, we present how vertebra extraction can
      efficiently be performed in exploiting the full computing power of parallel (GPU)
      and heterogeneous (multi-CPU/multi-GPU) architectures. We propose a parallel
      hybrid implementation of the most intensive steps enabling to boost performance.
      Experimentations have been conducted using a set of high-resolution X-ray medical
      images, showing a global speedup ranging from 3 to 22, by comparison with the CPU
      implementation. Data transfer times between CPU and GPU memories were included in
      the execution times of our proposed implementation.

PMID- 21860614
TI  - Feasibility of imaging myelin lesions in multiple sclerosis.
AB  - The goal of this study was to provide a feasibility assessment for PET imaging of
      multiple sclerosis (MS) lesions based on their decreased myelin content relative
      to the surrounding normal-appearing brain tissue. The imaging agent evaluated for
      this purpose is a molecule that binds strongly and specifically to myelin basic
      protein. Physiology-based pharmacokinetic modeling combined with PET image
      simulation applied to a brain model was used to examine whether such an agent
      would allow the differentiation of artificial lesions 4-10 mm in diameter from
      the surrounding normal-looking white and gray matter. Furthermore, we examined
      how changes in agent properties, model parameters, and experimental conditions
      can influence imageability, identifying a set of conditions under which imaging
      of MS lesions might be feasible. Based on our results, we concluded that PET
      imaging has the potential to become a useful complementary method to MRI for MS
      diagnosis and therapy monitoring.

PMID- 21860615
TI  - Impaired sympathoadrenal axis function contributes to enhanced insulin secretion
      in prediabetic obese rats.
AB  - The involvement of sympathoadrenal axis activity in obesity onset was
      investigated using the experimental model of treating neonatal rats with
      monosodium L-glutamate. To access general sympathetic nervous system activity, we
      recorded the firing rates of sympathetic superior cervical ganglion nerves in
      animals. Catecholamine content and secretion from isolated adrenal medulla were
      measured. Intravenous glucose tolerance test was performed, and isolated
      pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve
      firing rate of obese rats was decreased compared to the rate for lean rats. Basal
      catecholamine secretion decreased whereas catecholamine secretion induced by
      carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal
      medulla were all increased in obese rats compared to control. Both glucose
      intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline
      strongly inhibited glucose-induced insulin secretion in obese animals. These
      findings suggest that low sympathoadrenal activity contributes to impaired
      glycaemic control in prediabetic obese rats.

PMID- 21860616
TI  - Stepwise increases in left ventricular mass index and decreases in left
      ventricular ejection fraction correspond with the stages of chronic kidney
      disease in diabetes patients.
AB  - AIMS: Patients with diabetic nephropathy are reported to have a high prevalence
      of left ventricular structural and functional abnormalities. This study was
      designed to assess the determinants of left ventricular mass index (LVMI) and
      left ventricular ejection fraction (LVEF) in diabetic patients at various stages
      of chronic kidney disease (CKD). METHODS: This cross-sectional study enrolled 285
      diabetic patients with CKD stages 3 to 5 from our outpatient department of
      internal medicine. Clinical and echocardiographic parameters were compared and
      analyzed. RESULTS: We found a significant stepwise increase in LVMI (P < 0.001),
      LVH (P < 0.001), and LVEF <55% (P = 0.013) and a stepwise decrease in LVEF (P =
      0.038) corresponding to advance in CKD stages. CONCLUSIONS: Our findings suggest
      that increases in LVMI and decreases in LVEF coincide with advances in CKD stages
      in patients with diabetes.

PMID- 21860618
TI  - Construction and Antiapoptosis Activities of Recombinant Adenoviral Expression
      Vector Carrying EBV Latent Membrane Protein 2A.
AB  - To evaluate the possible effects of LMP2A (EBV latent membrane protein 2A) on
      human gastric cancer cell line SGC-7901, LMP2A coding gene was subcloned into
      shuttle plasmid pAdTrackCMV to form transfer plasmid pAdTrackCMV-2A, which was
      linearized with PmeI and cotransformed into E.coli BJ5183 with adenovirus genomic
      plasmid of pAdeasy-1. The identified recombinant adenovirus plasmid DNA was
      digested with PacI and transfected into 293 cells to package recombinant
      adenovirus particles named vAd-2A. Then the expression and antiapoptosis
      activities of LMP2A on SGC-7901 infected with vAd-2A were analyzed. The vAd-2A
      was successfully constructed and identified by PCR, restriction digestion, and
      sequencing. LMP2A expression in SGC was identified by strong green fluorescence
      expression with fluorescence microscopic photograph and Southern blotting. The
      growth of LMP2A expressing SGC cells was apparently improved. Both cyclin E
      expression and S phase ratio in LMP2A expressing SGC cells were upregulated by
      cell cycle analysis and confocal microscopic analysis respectively. The
      replication-deficient recombinant adenovirus vector can express LMP2A antigen in
      SGC cells and inhibit their apoptosis. The results indicate that LMP2A might play
      an important role in pathogenesis of EBV-associated gastric cancer (EBVaGC). This
      study establishes a foundation for further study on EBVaGC and its gene therapy.

PMID- 21860617
TI  - miRNAs and Melanoma: How Are They Connected?
AB  - miRNAs are non-coding RNAs that bind to mRNA targets and disturb their stability
      and/or translation, thus acting in gene posttranscriptional regulation. It is
      predicted that over 30% of mRNAs are regulated by miRNAs. Therefore these
      molecules are considered essential in the processing of many biological
      responses, such as cell proliferation, apoptosis, and stress responsiveness. As
      miRNAs participate of virtually all cellular pathways, their deregulation is
      critical to cancer development. Consequently, loss or gain of miRNAs function may
      contribute to tumor progression. Little is known about the regulation of miRNAs
      and understanding the events that lead to changes in their expression may provide
      new perspectives for cancer treatment. Among distinct types of cancer, melanoma
      has special implications. It is characterized as a complex disease, originated
      from a malignant transformation of melanocytes. Despite being rare, its
      metastatic form is usually incurable, which makes melanoma the major death cause
      of all skin cancers. Some molecular pathways are frequently disrupted in
      melanoma, and miRNAs probably have a decisive role on these alterations.
      Therefore, this review aims to discuss new findings about miRNAs in melanoma
      fields, underlying epigenetic processes, and also to argue possibilities of using
      miRNAs in melanoma diagnosis and therapy.

PMID- 21860619
TI  - EUS-Guided Biliary Drainage.
AB  - The echoendoscopic biliary drainage is an option to treat obstructive jaundices
      when ERCP drainage fails. These procedures compose alternative methods to the
      side of surgery and percutaneous transhepatic biliary drainage, and it was only
      possible by the continuous development and improvement of echoendoscopes and
      accessories. The development of linear setorial array echoendoscopes in early
      1990 brought a new approach to diagnostic and therapeutic dimenion on
      echoendoscopy capabilities, opening the possibility to perform punction over
      direct ultrasonographic view. Despite of the high success rate and low morbidity
      of biliary drainage obtained by ERCP, difficulty could be found at the presence
      of stent tumor ingrown, tumor gut compression, periampulary diverticula, and
      anatomic variation. The echoendoscopic technique starts performing punction and
      contrast of the left biliary tree. When performed from gastric wall, the access
      is made through hepatic segment III. From duodenum, direct common bile duct
      punction. Dilatation is required before stent introduction, and a plastic or
      metallic stent is introduced. This phrase should be replaced by: diathermic
      dilatation of the puncturing tract is required using a 6F cystostome. The
      technical success of hepaticogastrostomy is near 98%, and complications are
      present in 36%: pneumoperitoneum, choleperitoneum, infection, and stent
      disfunction. To prevent bile leakage, we have used the 2 stent techniques, the
      first stent introduced was a long uncovered metallic stent (8 or 10 cm), and
      inside this first stent a second fully covered stent of 6 cm was delivered to
      bridge the bile duct and the stomach. Choledochoduodenostomy overall success rate
      is 92% and described complications include, in frequency order, pneumoperitoneum
      and focal bile peritonitis, present in 19%. By the last 10 years, the technique
      was especially performed in reference centers, by ERCP experienced groups, and
      this seems to be a general guideline to safer procedure execution.

PMID- 21860620
TI  - Radiographic evaluation of children with febrile urinary tract infection: bottom
      up, top-down, or none of the above?
AB  - The proper algorithm for the radiographic evaluation of children with febrile
      urinary tract infection (FUTI) is hotly debated. Three studies are commonly
      administered: renal-bladder ultrasound (RUS), voiding cystourethrogram (VCUG),
      and dimercapto-succinic acid (DMSA) scan. However, the order in which these tests
      are obtained depends on the methodology followed: bottom-up or top-down. Each
      strategy carries advantages and disadvantages, and some groups now advocate even
      less of a workup (none of the above) due to the current controversies about
      treatment when abnormalities are diagnosed. New technology is available and still
      under investigation, but it may help to clarify the interplay between
      vesicoureteral reflux, renal scarring, and dysfunctional elimination in the
      future.

PMID- 21860621
TI  - Do telemedicine wound care specialist consults meet the needs of the referring
      physician? A survey of primary care providers.
AB  - The purpose of our study was to determine the factors that influence the use of
      telemedicine consultation by primary care physicians (PCPs) in the management of
      patients with problem wounds. A short questionnaire was administered to thirty
      six PCPs who referred to our Wound Care Program within one year. Participants
      were asked to rate the importance of specific concerns and benefits regarding the
      role of wound care surgical specialist (WCSS) and the use of telemedicine
      consults prior to possible face-to-face consultation. Sixty percent of
      respondents felt comfortable with telemedicine consultation based on
      recommendations alone. The total number of patients referred for telemedicine
      consult was 230, and face-to-face consultation with a WCSS was offered and
      arranged for 30% of patients. The perception of shared decision making,
      streamlining patient care, and an opportunity for followup were all highly ranked
      benefits. The majority of PCPs (93%) agreed that telemedicine wound care consult
      is a useful tool in their practice and would continue to use the telemedicine
      consult service.

PMID- 21860623
TI  - Enhancing facial esthetics by other modalities.
AB  - Preprosthetic surgeries are generally dealt with surgical procedures performed to
      facilitate fabrication of prosthesis or improve the prognosis of prosthodontic
      care. In general the surgical procedures include various soft and hard tissue
      procedures which are restricted intraorally. Maxillofacial prosthodontics is not
      restricted to restorations performed intra-orally. Various extraoral surgical
      procedures have come into light in the recent past which helps to improve the
      prosthodontic outcome of craniofacial region. The current paper tries to
      elaborate various minimally invasive cosmetic reconstructive procedures and
      materials available in recent times.

PMID- 21860624
TI  - Clinical usefulness of haptoglobin levels to evaluate hemolysis in recently
      transfused patients.
AB  - Introduction. Haptoglobin binds the globin portion of free hemoglobin. Serum
      haptoglobin measurement is used as a laboratory marker for the diagnosis of
      hemolytic anemia. Since stored blood contains free hemoglobin, transfusion may
      affect haptoglobin levels. Study Objectives. The aim of the study was to evaluate
      whether serum haptoglobin could be measured to assess hemolysis in recently
      transfused patients. Patients and Methods. Twenty-one patients, receiving more
      than one unit of packed red blood cells (PRBCs) for presumed nonhemolytic
      indications, were enrolled. Serum haptoglobin levels were recorded before,
      immediately after, and 24 and 48 hours after transfusion. Observations and
      Results. Analysis of variance with a repeated measures was used to examine the
      serum haptoglobin levels at different time periods and no significant difference
      was found (P = .28). Conclusion. The results suggest that serum haptoglobin can
      be used in the diagnosis of hemolysis in patients receiving multiple units of
      PRBC.

PMID- 21860625
TI  - Fatal retroperitoneal bleeding caused by metastasis of a sigmoid carcinoma.
AB  - Retroperitoneal bleeding is relatively rare and a potentially life-threatening
      condition with significant mortality. Early recognition requires a high index of
      suspicion. Increased life expectancy, the widespread use of anticoagulants, and
      the rise of endovascular interventions have caused an increase in the incidence
      of retroperitoneal bleeding. We present a case of a 74-year-old woman who died
      because of retroperitoneal bleeding caused by retroperitoneal metastasis of a
      sigmoid carcinoma with angioinvasive growth into a lumbar artery. In addition we
      discuss etiology, diagnostic management, and treatment strategy.

PMID- 21860622
TI  - Oxidative stress and air pollution exposure.
AB  - Air pollution is associated with increased cardiovascular and pulmonary morbidity
      and mortality. The mechanisms of air pollution-induced health effects involve
      oxidative stress and inflammation. As a matter of fact, particulate matter (PM),
      especially fine (PM(2.5), PM < 2.5 MUm) and ultrafine (PM(0.1), PM < 0.1 MUm)
      particles, ozone, nitrogen oxides, and transition metals, are potent oxidants or
      able to generate reactive oxygen species (ROS). Oxidative stress can trigger
      redox-sensitive pathways that lead to different biological processes such as
      inflammation and cell death. However, it does appear that the susceptibility of
      target organ to oxidative injury also depends upon its ability to upregulate
      protective scavenging systems. As vehicular traffic is known to importantly
      contribute to PM exposure, its intensity and quality must be strongly relevant
      determinants of the qualitative characteristics of PM spread in the atmosphere.
      Change in the composition of this PM is likely to modify its health impact.

PMID- 21860626
TI  - Extensive bilateral extraluminal perivascular pulmonary haemorrhage associated
      with stanford type a aortic dissection.
AB  - We present the case of an 80-year old man with a Stanford Type A dissecting
      thoracic aortic aneurysm plus the unusual CT finding of extramural haemorrhage
      along the pulmonary vessels. The clinical and radiological picture has an
      extremely high mortality.

PMID- 21860627
TI  - Provider Discussion, Education, and Question-Asking about Control Medications
      during Pediatric Asthma Visits.
AB  - Background. Few studies have explored how providers communicate about control
      medications during pediatric asthma visits. Objectives. The purpose of this study
      was to: (a) describe the extent to which providers discuss, educate, and ask
      children and their caregivers questions about control medications and (b) examine
      how child, caregiver, and provider characteristics are associated with provider
      communication about control medications during pediatric asthma visits. Methods.
      Children ages 8 through 16 with mild, moderate, or severe persistent asthma and
      their caregivers were recruited at five pediatric practices in nonurban areas of
      North Carolina. After audio-tape recording medical visits, caregivers completed
      questionnaires and children were interviewed. Generalized estimating equations
      were used to analyze the data. Results. Providers educated families about control
      medications during 61% of the visits, and they asked questions about control
      medications during 67% of visits. Providers were significantly more likely to
      discuss control medications if a child was taking a control medication, if the
      child had moderate to severe persistent asthma, and if the child was present for
      an asthma-related visit. Conclusion. Providers need to educate and ask more
      questions of families about side effects and how well control medications are
      working.

PMID- 21860628
TI  - International Journal of Pediatric Endocrinology: Excellence, accessibility,
      expansion, and evolution.

PMID- 21860629
TI  - Evolutionary fitness as a function of pubertal age in 22 subsistence-based
      traditional societies.
AB  - CONTEXT: The age of puberty has fallen over the past 130 years in industrialized,
      western countries, and this fall is widely referred to as the secular trend for
      earlier puberty. The current study was undertaken to test two evolutionary
      theories: (a) the reproductive system maximizes the number of offspring in
      response to positive environmental cues in terms of energy balance, and (b) early
      puberty is a trade-off response for high mortality rate and reduced resource
      availability. METHODS: Using a sample of 22 natural-fertility societies of mostly
      tropical foragers, horticulturalists, and pastoralists from Africa, South
      America, Australia, and Southeastern Asia, this study compares indices of
      adolescence growth and menarche with those of fertility fitness in these non
      industrial, traditional societies. RESULTS: The average age at menarche
      correlated with the first reproduction, but did not correlate with the total
      fertility rate TFR or reproductive fitness. The age at menarche correlated
      negatively with their average adult body mass, and the average adult body weight
      positively correlated with reproductive fitness. Survivorship did not correlate
      with the age at menarche or age indices of the adolescent growth spurt. The
      population density correlated positively with the age at first reproduction, but
      not with menarche age, TFR, or reproductive fitness. CONCLUSIONS: Based on our
      analyses, we reject the working hypotheses that reproductive fitness is enhanced
      in societies with early puberty or that early menarche is an adaptive response to
      greater mortality risk. Whereas body mass is a measure of resources is tightly
      associated with fitness, the age of menarche is not.

PMID- 21860630
TI  - Resistance to thyroid hormone associated with a novel mutation of the thyroid
      beta receptor gene in a four-year-old female.
AB  - Resistance to thyroid hormone (RTH) is a rare syndrome of reduced responsiveness
      of target tissues to thyroid hormone and is caused mutation in the thyroid beta
      receptor gene. We report a novel mutation, E445X, causing RTH in a 4-year old
      girl. The patient exhibited extreme signs and symptoms of RTH at an early age,
      and had a large compressive goiter. Following total extracapsular thyroidectomy,
      upper airway compression was relieved and symptoms of hyperthyroidism improved.
      This case appears to be the youngest child recorded to have undergone total
      thyroidectomy for RTH. Post-operative TSH elevations were managed with every
      other-day triiodothyronine therapy.

PMID- 21860632
TI  - Early onset obesity and adrenal insufficiency associated with a homozygous POMC
      mutation.
AB  - Isolated hypocortisolism due to ACTH deficiency is a rare condition that can be
      caused by homozygous or compound heterozygous mutations in the gene encoding
      proopiomelanocortin (POMC). Loss of function mutations of POMC gene typically
      results in adrenal insufficiency, obesity and red hair. We describe an 18 month
      old Hispanic female with congenital adrenal insufficiency, a novel POMC mutation
      and atypical clinical features. The patient presented at the age of 9 months with
      hypoglycemia and the endocrine evaluation resulted in a diagnosis of ACTH
      deficiency. She developed extreme weight gain prompting sequence analysis of
      POMC, which revealed a homozygous c.231C > A change which is predicted to result
      in a premature termination codon. The case we report had obesity, hypocortisolism
      but lacked red hair which is typical for subjects with POMC mutations. Mutations
      of POMC should be considered in individuals with severe early onset obesity and
      adrenal insufficiency even when they lack the typical pigmentary phenotype.

PMID- 21860631
TI  - Prevention of Vitamin D deficiency in infancy: daily 400 IU vitamin D is
      sufficient.
AB  - SUMMARY: AIM-OBJECTIVE: Vitamin D deficiency and rickets in developing countries
      continues to be a major health problem. Additionally, the increase of cases of
      rickets in children of some ethnic groups in the United States and European
      countries has provided this issue to be updated. Obviously, powerful strategies
      are necessary to prevent vitamin D deficiency nation-wide. In 2005, a nationwide
      prevention program for vitamin D deficiency was initiated, recommending 400 IU
      vitamin D per a day. This study was designed to evaluate the efficacy of the
      prevention program. METHODS: Eighty-five infants who were recalled as part of the
      national screening program for congenital hypothyroidism between February 2010
      and August 2010 at Kocaeli University Children's Hospital were evaluated in terms
      of their vitamin D status as well. All babies had been provided with free vitamin
      D (Cholecalciferol) solution and recommended to receive 400 IU (3 drops) daily.
      Information regarding the age at start of supplementation, the dosage and
      compliance were obtained from the mothers with face-to-face interview. Serum 25
      hydroxy vitamin D (25-OH-D), alkaline phosphatase (AP), parathormone (PTH) levels
      were measured. RESULTS: The mean age at which Vitamin D3 supplementation began
      was 16.5 +/- 20.7 (3-120) days. Ninety percent of cases (n:76) were receiving 3
      drops (400 IU) vitamin D3 per day as recommended; 70% of cases (n:59) were given
      vitamin D3 regularly, the remainder had imperfect compliance. Among those
      children who are older than 12 months, only 20% continued vitamin D
      supplementation. No subject had clinical signs of rickets. The mean 25-OH-D level
      was 42,5 +/- 25,8 (median: 38.3) ng/ml. Ten subjects (12%) had their serum 25-OH
      D levels lower than 20 ng/ml (6 between 15-20 ng/ml, 3 between 5-15 ng/ml and
      only one < 5 ng/ml). CONCLUSIONS: 400 U/day vitamin D seems adequate to prevent
      vitamin D deficiency. However, we believe that the program for preventing vitamin
      D deficiency in Turkey, needs to be reinforced to start immediately after birth,
      and to continue beyond 1 year of age at 400U regular daily dosage.

PMID- 21860633
TI  - Efficacy of Leuprolide Acetate 1-Month Depot for Central Precocious Puberty
      (CPP): Growth Outcomes During a Prospective, Longitudinal Study.
AB  - INTRODUCTION: Gonadotropin-releasing hormone analogs (GnRHa) are the treatment of
      choice for CPP. We investigated growth in GnRHa-naive subjects, treated with
      leuprolide acetate 1-month depot for CPP. METHODS: This prospective, open-label
      study had a long-term, observational, follow-up period. Forty-nine females and 6
      males were enrolled. Leuprolide acetate depot was administered intramuscularly
      every 28 days. Height and growth rate during and after treatment until adulthood
      were measured. RESULTS: Among 30 of 49 females having an adult height (AH)
      measurement, 29 had target heights available (mean = 163.8 cm) and 27 had
      pretreatment predicted adult heights (PAHs; mean = 157.4 cm). After treatment,
      the mean AH at mean age 21.8 years [range 13.7-26.7 years] was 162.5 cm, a mean
      height gain over baseline PAH of 4.0 cm. The mean height standard deviation score
      was -0.1 at AH. CONCLUSIONS: Treatment of CPP with leuprolide acetate 1-month
      depot had beneficial effects on growth rate and preservation of AH. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00660010.

PMID- 21860634
TI  - The significance of the j-curve in hypertension and coronary artery diseases.
AB  - The J-curve effect describes an inverse relation between low blood pressure (BP)
      and cardiovascular complications. This effect is more pronounced in patients with
      preexisting coronary artery disease (CAD), hypertension or left ventricular
      hypertrophy (LVH). The recent large clinical outcomes trials have observed a J
      curve effect between a diastolic BP of 70-80 mmHg as well as a systolic BP <130
      mmHg. The J-curve phenomenon does not appear in stroke or renal disease. This is
      because the coronary arteries are perfused during diastole, but the cerebral and
      renal perfusion mainly occurs in systole. Therefore, caution should be taken to
      maintain the diastolic blood pressure (DBP) at minimum of 70 mmHg and possibly to
      maintain the DBP between 80-85 mmHg in patients with severe LVH, CAD or vascular
      diseases. BP control in high-risk elderly patients should be carefully done as
      undergoing aggressive therapy to lower the systolic blood pressure below 140 mmHg
      can cause cardiovascular complications due to the severely reduced DBP and
      increased pulse pressure.

PMID- 21860635
TI  - Prognostic Impact of Early ST-Segment Resolution and Biochemical Markers in
      Patients With ST-Elevation Myocardial Infarction.

PMID- 21860636
TI  - Intermediate and long-term results of transcatheter closure of patent foramen
      ovale using the amplatzer patent foramen ovale occluder: one case of pulmonary
      embolism irrespective of patent foramen ovale closure.
AB  - BACKGROUND AND OBJECTIVES: Patent foramen ovale (PFO) has been implicated in the
      pathogenesis of cryptogenic stroke or transient ischemic attack (TIA) due to
      paradoxical embolism, and in the pathogenesis of migraine. This paper reports the
      intermediate and long-term results of transcatheter closure of PFO associated
      with cerebrovascular accidents (CVAs), TIAs and migraine, using the Amplatzer PFO
      occluder. This paper also reports a case of pulmonary embolism which developed in
      one patient after PFO closure. SUBJECTS AND METHODS: From January 2003 to May
      2010, 16 patients with PFO (seven males and nine females) with a history of at
      least one episode of cryptogenic stroke/TIA, CVA, or migraine and who underwent
      percutaneous transcatheter closure of PFO using the Amplatzer occluder. All the
      procedures were performed under general anesthesia and were assisted by
      transesophageal echocardiography. RESULTS: The device was implanted without any
      significant complications in all the patients, and the PFOs were effectively
      closed. At an average follow-up period of 54 months, the 15 patients with TIA/CVA
      had no recurrence of any thromboembolic event. The symptoms in one patient with
      migraine subsided after occlusion of the PFO. In this study, pulmonary embolism
      occurred five months after PFO closure in one patient, but the cause of pulmonary
      embolism was not identified. However, it is believed that the pulmonary embolism
      occurred without stroke recurrence because occlusion of the PFO was performed
      when the patient had a stroke event. CONCLUSION: It can be concluded that
      according to the intermediate and long-term follow-up results, transcatheter PFO
      closure is an effective and safe therapeutic modality in the prevention of
      thromboembolic events, especially in the patients with cryptogenic stroke/TIA,
      and PFO closure is helpful in the treatment of migraine. However, this study
      involved a small number of patients and also the follow-up period was not long
      enough. Hence, randomized, controlled trials are necessary to determine if this
      approach is preferable to medical therapy for the prevention of recurrent stroke
      or as primary treatment for patients with migraine headache.

PMID- 21860637
TI  - Characteristics, outcomes and predictors of long-term mortality for patients
      hospitalized for acute heart failure: a report from the korean heart failure
      registry.
AB  - BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) is associated with a poor
      prognosis and it requires repeated hospitalizations. However, there are few
      studies on the characteristics, treatment and prognostic factors of AHF. The aims
      of this study were to describe the clinical characteristics, management and
      outcomes of the patients hospitalized for AHF in Korea. SUBJECTS AND METHODS: We
      analyzed the clinical data of 3,200 hospitalization episodes that were recorded
      between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry
      database. The mean age was 67.6+/-14.3 years and 50% of the patients were female.
      RESULTS: Twenty-nine point six percent (29.6%) of the patients had a history of
      previous HF and 52.3% of the patients had ischemic heart disease. Left
      ventricular ejection fraction (LVEF) was reported for 89% of the patients. The
      mean LVEF was 38.5+/-15.7% and 26.1% of the patients had preserved systolic
      function (LVEF >=50%), which was more prevalent in the females (34.0% vs. 18.4%,
      respectively, p<0.001). At discharge, 58.6% of the patients received beta
      blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or
      angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and
      ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%,
      respectively. Multivariate analysis revealed that advanced age {hazard ratio:
      1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of
      heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063);
      p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N
      terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849);
      p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were
      significantly associated with total death. CONCLUSION: We present here the
      characteristics and prognosis of an unselected population of AHF patients in
      Korea. The long-term mortality rate was comparable to that reported in other
      countries. The independent clinical risk factors included age, a previous history
      of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at
      discharge.

PMID- 21860638
TI  - Combined Assessments of Biochemical Markers and ST-Segment Resolution Provide
      Additional Prognostic Information for Patients With ST-Segment Elevation
      Myocardial Infarction.
AB  - BACKGROUND AND OBJECTIVES: The prognostic value of biochemical markers and the
      resolution of ST-segment elevation on electrocardiogram are well established.
      However, how a combination of these two tools affects the evaluation of risk
      stratification has not yet been evaluated. SUBJECTS AND METHODS: Between January
      2006 and June 2008, 178 consecutive patients treated with primary percutaneous
      coronary interventions after ST-segment elevation myocardial infarctions (STEMI)
      were analyzed at two coronary care units. Patients were divided into the
      following three groups according to ST-segment resolution: complete (>=70%
      depression of the elevated ST-segment, n=63), partial (30% to 70%, n=90), and
      incomplete (<30%, n=25). Demographic data, including history,
      electrocardiography, biochemical markers, initial ejection fraction, and
      angiographic findings were also evaluated. RESULTS: There were 7 deaths, 3
      repeated myocardial infarctions, and 17 readmissions for worsening heart failure
      during six months of follow-up. In a multivariate analysis to predict clinical
      outcomes, ejection fraction {hazard ratio (HR): 0.83 (0.76-0.91), p<0.01}, high
      sensitivity C-reactive protein {HR: 1.15 (1.05-1.26), p<0.05}, and the degree of
      ST-segment resolution {HR: 0.96 (0.93-0.09), p<0.05} were independently
      associated with clinical outcomes. According to the Cox-proportional hazards
      model, the addition of ST-segment resolution markedly improved the prognostic
      utility of the model containing biochemical markers and ejection fraction.
      CONCLUSION: Assessment of biomarkers upon admission and ST-segment resolution are
      strong predictors of clinical outcomes. The combination of these data provides
      additive information about prognosis at an early point in the disease progression
      and further improves risk stratification for STEMI.

PMID- 21860639
TI  - Parameters to guide retreatment after initial intravenous immunoglobulin therapy
      in kawasaki disease.
AB  - BACKGROUND AND OBJECTIVES: We sought to determine parameters to guide the
      decision of retreatment in patients with Kawasaki disease (KD) who remained
      febrile after initial intravenous immunoglobulin (IVIG). SUBJECTS AND METHODS: A
      total of 129 children with KD were studied prospectively. Patients were treated
      with IVIG 2 to 9 days after the onset of disease. Laboratory measures, such as
      white blood cell (WBC), percentage of neutrophils, C-reactive protein (CRP), and
      N-terminal pro-brain natriuretic peptide (NT-proBNP), were determined before and
      48 to 72 hours after IVIG treatment. Patients were classified into IVIG
      responsive and IVIG-resistant groups, based on the response to IVIG. RESULTS: Of
      a total of 129 patients, 107 patients (83%) completely responded to a single IVIG
      therapy and only 22 patients (17%) required retreatment: 14 had persistent fever
      and 8 had recrudescent fever. There was no significant difference between the
      groups in age, gender distribution, and duration of fever to IVIG initiation, but
      coronary artery lesions developed significantly more often in the resistant group
      than in the responsive group (31.8% vs. 2.8%, p=0.000). Compared with pre-IVIG
      data, post-IVIG levels of WBC, percentage of neutrophils, CRP, and NT-proBNP
      decreased to within the normal range in the responsive group, whereas they
      remained high in the resistant group. Multivariate logistic regression indicated
      that neutrophil counts, CRP, and NT-proBNP were independent parameters of
      retreatment. CONCLUSION: Additional therapy at an early stage of the disease
      should be administered for febrile patients who have high values of CRP, NT
      proBNP, and/or neutrophil counts after IVIG therapy.

PMID- 21860640
TI  - Deoxyribonucleic Acid copy number aberrations in vasospastic angina patients
      using an array comparative genomic hybridization.
AB  - BACKGROUND AND OBJECTIVES: Vasospastic angina (VA) is a specific type of coronary
      artery disease and develops as a result of coronary artery spasm. Recently, a few
      studies have revealed that VA caused by coronary artery spasm is related to
      genetic traits. The objective of this study was to use the recently developed
      technique of array comparative genomic hybridization (CGH) to screen the genetic
      aberrations of VA. SUBJECTS AND METHODS: To identify candidate genes that might
      be causally involved in the pathogenesis of VA, genomic deoxyribonucleic acids
      were extracted from whole blood of 28 patients with VA who presented at
      Department of Cardiology at Seoul St. Mary's Hospital, Seoul, Korea. The copy
      number profiles of these patients was then analyzed using array CGH and reverse
      transcriptase (RT) quantitative polymerase chain reaction (PCR). RESULTS: Array
      CGH revealed gains in 31 different regions, with losses in the 4q35.2, 7q22.1,
      10q26.3, 15q11.2, 16p13.11, 17p11.2 and 19q13.3 regions (more than 32% aberration
      in these regions). Several loci were found to be frequently including gains of 5p
      and 11q (50% of samples). The most common losses were found in 7q (54% of
      samples). Copy number aberrations in chromosomal regions were detected and
      corresponding genes were confirmed by RT quantitative PCR. The fold change levels
      were highest in the CTDP1 (18q23), HDAC10 (22q13.33), KCNQ1 (11p15.5-p15.4),
      NINJ2 (12p13.33), NOTCH2 (1p12-p11.2), PCSK6 (15q26.3), SDHA (5p15.33), and MUC17
      (7q22.1) genes. CONCLUSION: Many candidate chromosomal regions that might be
      related to the pathogenesis of VA were detected by array CGH and should be
      systematically investigated to establish the causative and specific genes for VA.

PMID- 21860641
TI  - Associated symptoms of kawasaki disease.
AB  - BACKGROUND AND OBJECTIVES: In addition to diagnostic criteria, a broad range of
      nonspecific clinical features can be found in patients with Kawasaki disease.
      This lack of specificity may cause confusion with other febrile illnesses and
      delay the diagnosis of Kawasaki disease. The purpose of this study is to describe
      common associated symptoms and their clinical significances in children affected
      with Kawasaki disease. SUBJECTS AND METHODS: As a retrospective study, we
      reviewed the medical records of 121 children who were treated for Kawasaki
      disease at Presbyterian medical center from January 2005 to June 2010. All
      clinical symptoms, laboratory data and echocardiographic findings in patients
      with KD were collected and analyzed. RESULTS: We found that there are 9
      associated symptoms, namely cough, rhinorrhea, sputum, abdominal pain, vomiting,
      diarrhea, arthralgia, headache and seizure, which occur in patients with Kawasaki
      disease. Among the study group, there were only 32 children with no associated
      symptoms (26.4%). Patients with abdominal pain and headache had an older mean age
      than those without such symptoms. The incidence of seizure was significantly
      higher in incomplete Kawasaki disease patients compared with those with complete
      Kawasaki disease. Vomiting was highly associated with IVIG non-responder group.
      CONCLUSION: To decrease the incidence of serious coronary complications due to
      delayed diagnosis, physicians need to be aware of the manifestations of Kawasaki
      disease and the possibility of associated symptoms, which, being unspecific, may
      otherwise not raise any red flags.

PMID- 21860642
TI  - Aseptic Endocarditis in Behcet's Disease Presenting as Tricuspid Valve Stenosis.
AB  - Aseptic endocarditis is an uncommon complication of Behcet's disease (BD). We
      describe a rare case of a 39-year-old female who had BD with aseptic endocarditis
      of the tricuspid valve (TV) presenting as tricuspid stenosis. She was diagnosed
      with BD four years ago. The mucocutaneous lesions were well-controlled with
      colchicine and short courses of corticosteroids. She remained free of signs and
      symptoms of BD for one year without any medication. Three months before
      admission, she gradually developed dyspnea on exertion and peripheral edema.
      Echocardiography revealed dilated right atrium and markedly thickened TV with
      severe stenosis. TV replacement was performed. Pathologic examination of the
      valve showed fibrinoid necrotic material and inflammatory cell infiltration.
      Blood cultures and cultures of the excised valve were negative for
      microorganisms.

PMID- 21860643
TI  - Percutaneous transseptal left atrial drainage for decompression of the left heart
      in an adult patient during percutaneous cardiopulmonary support.
AB  - A 28-year-old male with hemophagocytic lymphohistiocytosis presented with left
      ventricular dysfunction and cardiac arrest. Percutaneous cardiopulmonary support
      (PCPS) was initiated, but left heart distension developed with associated
      aggravation of pulmonary edema. Percutaneous transseptal left atrial sheath (28
      Fr) drainage was incorporated into the PCPS venous circuit under fluoroscopic
      guidance to enable left heart decompression 1 days after PCPS initiation. The
      patient's pulmonary edema improved markedly, and distention of his left heart
      diminished. He was successfully weaned from PCPS 5 days later. Percutaneous
      transseptal left atrial drainage with large venous cannulae is feasible and
      effective in decompressing the left heart in adult patients during PCPS.

PMID- 21860644
TI  - Procedure-induced acute common carotid artery perforation presenting with airway
      obstruction and successful treatment by endovascular stent graft.
AB  - A 63-year-old female was admitted to our hospital for catheter ablation during
      atrial fibrillation. After catheter ablation, the patient was transferred to the
      cardiac care unit and mechanically ventilated due to dyspnea and hypotension.
      Imaging showed active bleeding from the right common carotid artery (CCA) with
      extensive hematoma into the mediastinum. She was successfully treated with a
      stent graft at the CCA. Further bleeding or neurologic sequel did not occur after
      treatment.

PMID- 21860645
TI  - Late stent thrombosis after drug-eluting stent implantation: a rare case of
      accelerated neo-atherosclerosis and early manifestation of neointimal rupture.
AB  - An 80-year old woman suffered from sudden onset of chest pain and dyspnea, and
      visited the emergency room. She received stent implantation with a biolimus A9
      eluting stent (Nobori(r) 3.0*24 mm) at a the mid-portion of the left anterior
      descending artery 5 months prior to admission. The emergency 5-month follow-up
      angiogram was performed under the impression of late stent thrombosis. The follow
      up angiogram showed subtotal occlusion at the mid-portion of the left anterior
      descending artery, which was the same segment of previous stent implantation 5
      months ago. Immediately after thrombus aspiration with the thrombus aspiration
      catheter, the optical coherence tomography showed layered appearance of
      neointimal hyperplasia and neointimal rupture within the previously stented
      segment. Thus, neointimal rupture within accelerated growth of neointimal tissue
      was observed within a relatively shorter period (i.e., about 5 months) after
      stent implantation.

PMID- 21860646
TI  - Hybrid approach for the treatment of thoracic aortic arch aneurysm in a patient
      with chronic obstructive lung disease and retrosternal adhesion.
AB  - A 73-year-old woman with a history of chronic hypertension and severe chronic
      obstructive pulmonary disease, presented to a district general hospital with
      thoracic pain in a profound state of shock. She was diagnosed with cardiac
      tamponade, severe mitral regurgitation, and Stanford type A (Debakey type I)
      intramural hematoma. Her ascending aorta was of a significant size and therefore
      emergent repair was done to replace the ascending aorta and mitral valve. After 6
      months, an increased aneurysmal size of 6.0 cm was observed in a follow up
      contrast-enhanced computed tomography angiography. The patient was successfully
      treated by a staged hybrid procedure involving initial supra-aortic
      reconstruction.

PMID- 21860647
TI  - Very Late Stent Thrombosis in a Drug-Eluting Stent due to Interruption of Anti
      Platelet Agents in Patients With Acute Myocardial Infarction and Thrombocytosis.
AB  - Stent thrombosis is a fatal complication in patients who have undergone
      percutaneous coronary intervention, and discontinuation of anti-platelet agent is
      a major risk factor of stent thrombosis. We report a rare case of very late stent
      thrombosis (VLST) following discontinuation of anti-platelet agents in a patient
      who experienced acute myocardial infarction and essential thrombocytosis. She had
      undergone implantation of a drug eluting stent (DES) and a bare metal stent (BMS)
      two and half years prior to her presentation. VLST developed in DES, not in BMS,
      following interruption of anti-platelet therapy.

PMID- 21860648
TI  - Heavy coronary calcium mimicking in-stent restenosis.

PMID- 21860649
TI  - Are Toll-like receptors and decoy receptors involved in the immunopathogenesis of
      systemic lupus erythematosus and lupus-like syndromes?
AB  - In this paper we focus our attention on the role of two families of receptors,
      Toll-like receptors (TLR) and decoy receptors (DcR) involved in the generation of
      systemic lupus erythematosus (SLE) and lupus-like syndromes in human and mouse
      models. To date, these molecules were described in several autoimmune disorders
      such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and
      SLE. Here, we summarize the findings of recent investigations on TLR and DcR and
      their role in the immunopathogenesis of the SLE.

PMID- 21860650
TI  - CI431, an Aqueous Compound from Ciona intestinalis L., Induces Apoptosis through
      a Mitochondria-Mediated Pathway in Human Hepatocellular Carcinoma Cells.
AB  - In the present studies, a novel compound with potent anti-tumor activity from
      Ciona intestinalis L. was purified by acetone fractionation, ultrafiltration, gel
      chromatography and High Performance Liquid Chromatography. The molecular weight
      of the highly purified compound, designated CI431, was 431Da as determined by
      HPLC-MS analysis. CI431 exhibited significant cytotoxicity to several cancer cell
      types. However, only a slight inhibitory effect was found when treating the
      benign human liver cell line BEL-7702 with the compound. To explore its mechanism
      against hepatocellular carcinoma, BEL-7402 cells were treated with CI431 in
      vitro. We found that CI431 induced apoptotic death in BEL-7402 cells in a dose-
      and time-dependent manner. Cell cycle analysis demonstrated that CI431 caused
      cell cycle arrest at the G2/M phase, and a sub-G1 peak appeared after 24 h. The
      mitochondrial-mediated pathway was implicated in this CI431-induced apoptosis as
      evidenced by the disruption of mitochondrial membrane potential. The results
      suggest that the CI431 induces apoptosis in BEL-7402 human hepatoma cells by
      intrinsic mitochondrial pathway.

PMID- 21860651
TI  - Bio-prospecting of a few brown seaweeds for their cytotoxic and antioxidant
      activities.
AB  - Methanolic extracts (MEs) of seven brown seaweeds occurring in the Indian coastal
      waters were screened for their cytotoxic and antioxidant properties following
      various assays. The methanolic extracts of seaweeds in the order of Dictyopteris
      australis > Spatoglossum variabile > Stoechospermum marginatum > Spatoglossum
      aspermum showed significant cytotoxic activity. A very high DPPH radical
      scavenging activity was exhibited by the methanolic extracts prepared from St.
      marginatum, Padina tetrastromatica, Dictyopteris delicatula and S. aspermum. The
      total phenolic content of the MEs varied from 13.19 +/- 0.32 to 25.29 +/- 0.445
      gallic acid equivalents (mg g(-1) of methanolic extract). The reducing power
      assay indicated a dose dependency, at concentrations of 0.1, 0.5 and 1.0 and 2.0
      mg mL(-1) of MEs and decreased in the following order: Butylated hydroxy toluene
      > P. tetrastromatica > D. delicatula > S. aspermum > S. variabile > S. marginatum
      > D. australis > S. marginatum. Furthermore, D. australis, S. aspermum, S.
      variabile and S. marginatum demonstrated good metal ion chelating properties. All
      the above evidences suggest that, the antioxidant compounds found in brown
      seaweeds scavenge free radicals through effective intervention. This decisively
      promotes them as a potential source of natural antioxidants.

PMID- 21860652
TI  - Relationships among Constitution, Stress, and Discomfort in the First Trimester.
AB  - The purpose of this study was to explore correlations among constitution, stress,
      and discomfort symptoms during the first trimester of pregnancy. We adopted a
      descriptive and correlational research design and collected data from 261
      pregnant women during their first trimester in southern Taiwan using structured
      questionnaires. Results showed that (1) stress was significantly and positively
      correlated with Yang-Xu, Yin-Xu, and Tan-Shi-Yu-Zhi constitutions, respectively;
      (2) Yin-Xu and Tan-Shi-Yu-Zhi constitutions had significant correlations with all
      symptoms of discomfort, while Yang-Xu had significant correlations with all
      symptoms of discomfort except for "running nose"; (3) Tan-Shi-Yu-Zhi constitution
      and stress were two indicators for "fatigue"; Tan-Shi-Yu-Zhi was the indicator
      for "nausea"; Yang-Xu and Yin-Xu were indicators for "frequent urination." Our
      findings also indicate that stress level affects constitutional changes and that
      stress and constitutional change affect the incidence of discomfort. This
      research can help healthcare professionals observe these discomforts and provide
      individualized care for pregnant women, to nurture pregnant women into neutral
      type constitution, minimize their levels of discomfort, and promote the health of
      the fetus and the mother.

PMID- 21860653
TI  - Effect of Electroacupuncture on Activation of p38MAPK in Spinal Dorsal Horn in
      Rats with Complete Freund's Adjuvant-Induced Inflammatory Pain.
AB  - Activation of mitogen-activated protein kinases (MAPKs), especially p38 MAPK,
      plays an important role in the development of central sensitization related to
      persistent inflammatory pain. Electroacupuncture (EA) is well known to relieve
      persistent inflammatory pain. However, little is known about relationship between
      EA and p38 MAPK. Inflammatory pain rat model was induced by intraplantar
      injection of complete Freund's adjuvant (CFA). Male adult SD rats were randomly
      divided into the saline group, CFA group, and CFA + EA group. EA (constant
      saquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1
      to 2 mA) was applied to bilateral "Zusanli" (ST 36) and "Kunlun" acupoints (BL
      60) for 30 min, once per day. The paw edema and paw withdrawal threshold (PWT)
      were measured at preinjection and days postinjection 1, 3, and 14. Spinal p
      p38MAPK- immunoreactivty (p-p38MAPK-IR) cells were detected by
      immunohistochemistry at postinjection day 3 and 14. EA significantly inhibited
      paw edema at postinjection days 14 and increased PWT at postinjection days 3 and
      14. Moreover, the increasing number of spinal p-p38MAPK-IR cells which was
      induced by CFA injection was suppressed by EA stimulation. These results indicate
      that anti-inflammatory and analgesic effect of EA might be associated with its
      inhibition of spinal p38 MAPK activation and thereby provide a potential
      mechanism for the treatment of inflammatory pain by EA.

PMID- 21860654
TI  - Association of the Apolipoprotein A5 Gene -1131T>C Polymorphism with Serum Lipids
      in Korean Subjects: Impact of Sasang Constitution.
AB  - Apolipoprotein A5 (APOA5) was identified as a strong modulator of serum lipids.
      Moreover, an APOA5 gene -1131T>C polymorphism has been associated with serum
      lipids, but the results are inconsistent according to ethnic and racial groups.
      We have genotyped and analyzed 1,619 outpatients of Korean oriental medicine
      hospitals who were classified into three Sasang constitution groups (SCGs), So
      Yang (SY), So-Eum (SE), and Tae-Eum (TE). There were no significant difference in
      the distribution of the APOA5 -1131T>C genotype among the three SCGs. Subjects
      with the C allele in SY and TE showed significantly lower serum high-density
      lipoprotein cholesterol (HDL-C) and higher triglyceride (TG) levels than
      noncarriers of the C allele. These results show the differences in the prevalence
      of decreasing serum HDL-C and elevating serum TG levels along with APOA5 -1131T>C
      polymorphism according to SCG and suggest that SCG may act as a significant risk
      factor for hypo-HDL-C-emia and hypertriglyceridemia susceptibility.

PMID- 21860655
TI  - Ligustrazine injection for chronic pulmonary heart disease: a systematic review
      and meta-analysis.
AB  - Objective. This study was intended to evaluate the efficacy and safety of
      ligustrazine injection for chronic pulmonary heart disease (CPHD). Method.
      Randomized controlled trials (RCTs) of clinical therapeutic studies on CPHD when
      using ligustrazine injection were included. Searches were applied to the
      following electronic databases: the PubMed, the Cochrane Library, EMBASE, CBM,
      and AMED. No language restriction was used. All trials included were analyzed
      according to the criteria of the Cochrane Handbook. Review Manager 5.0 software
      was used for data analysis. Result. 34 RCTs with low methodological quality were
      included. Compared to conventional medicine treatment alone, ligustrazine
      injection plus conventional medicine treatment showed improvement in New York
      Heart Association classification of clinical status (Odds ratio 0.22; 95% CI 0.17
      to 0.28) and depression of pulmonary artery hypertension (weighted mean
      difference -4.77; 95% CI -5.85 to -3.68). Three studies had reported adverse
      events. No serious adverse effects were reported. Conclusion. While there is some
      evidence that suggests potential effectiveness of ligustrazine injection for
      CPHD, the results were limited by the methodological flaws of the studies. High
      quality studies are needed to provide clear evidence for the future use of
      ligustrazine injection.

PMID- 21860656
TI  - The applications and obstacles of metabonomics in traditional chinese medicine.
AB  - In the recent years, a wide range of metabonomic technologies are widely used in
      the modern research of traditional chinese medicine (TCM). At present, the most
      prevailing methods for TCM research are mainly nuclear magnetic resonance (NMR),
      gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass
      spectrometry (LC-MS). With these techniques, metabonomics will help to understand
      syndromes, efficacy and toxicity of TCM. However, every analytical technique has
      its advantages and drawbacks, and there exist some obstacles of its applications
      on TCM. So, we discuss metabonomics in TCM and analyze some problems of its
      applications to study TCM in recent years. We believe that with the further
      development of metabonomic analytical technology, especially multianalysed
      techniques, metabonomics will greatly promote TCM research and be beneficial to
      the modernization of TCM.

PMID- 21860657
TI  - Salvianolic Acid B Inhibits ERK and p38 MAPK Signaling in TGF-beta1-Stimulated
      Human Hepatic Stellate Cell Line (LX-2) via Distinct Pathways.
AB  - Salvianolic acid B (SA-B) is water-soluble component of Radix Salvia
      miltiorrhiza. The previous work indicated that SA-B can inhibit MAPK and Smad
      signaling in activated hepatic stellate cells (HSCs) to perform anti-fibrotic
      activity Lv et al. 2010. However, some studies have shown that there is cross
      talk between MAPK and Smad in certain cell types. Thus, the anti-fibrotic action
      of SA-B may be through the cross-talk. In order to clarify the mechanism of SA-B
      further, we knocked down Smad in LX-2 cells (SRV4) via RNAi, and then added TGF
      beta1, and PD98059 or SB203580 and SA-B. The levels of p-MEK and p-p38 were
      inhibited by SA-B in SRV4 independent of TGF-beta1. The expression of Col I and
      alpha-SMA in SRV4 could be reduced by SA-B independent TGF-beta1. SB203580 had
      not significant effect on p-MEK in SRV4 stimulated by TGF-beta1. The levels of p
      MEK in SRV4 were not increased significantly after TGF-beta1 stimulation. PD98059
      had no effect on the levels of p-p38 in SRV4 irrespective of TGF-beta1. In
      conclusion, SA-B inhibits the synthesis of Col I in LX-2 cells independent of TGF
      beta1 stimulation, and the anti-fibrotic effect of SA-B is due to direct
      inhibition of p38 signaling and inhibition the cross-talk of Smad to ERK
      signaling.

PMID- 21860658
TI  - The failure of R0.
AB  - The basic reproductive ratio, R(0), is one of the fundamental concepts in
      mathematical biology. It is a threshold parameter, intended to quantify the
      spread of disease by estimating the average number of secondary infections in a
      wholly susceptible population, giving an indication of the invasion strength of
      an epidemic: if R(0) < 1, the disease dies out, whereas if R(0) > 1, the disease
      persists. R(0) has been widely used as a measure of disease strength to estimate
      the effectiveness of control measures and to form the backbone of disease
      management policy. However, in almost every aspect that matters, R(0) is flawed.
      Diseases can persist with R(0) < 1, while diseases with R(0) > 1 can die out. We
      show that the same model of malaria gives many different values of R(0),
      depending on the method used, with the sole common property that they have a
      threshold at 1. We also survey estimated values of R(0) for a variety of
      diseases, and examine some of the alternatives that have been proposed. If R(0)
      is to be used, it must be accompanied by caveats about the method of calculation,
      underlying model assumptions and evidence that it is actually a threshold.
      Otherwise, the concept is meaningless.

PMID- 21860659
TI  - Health literacy in diabetes care: explanation, evidence and equipment.
AB  - The exchange of complex health information among patients, providers, health
      organizations and the public is often described as health literacy. Low levels of
      health literacy is common and associated with processes of healthcare and
      important health outcomes. In diabetes, health literacy is related to diabetes
      knowledge, self-efficacy and self-care behaviors and glycemic control. Health
      literacy may also provide a better understanding of racial disparities observed
      in patients with diabetes. Strategies to address health literacy, based upon this
      understanding of its role, provide a means to improve diabetes care. This article
      describes the concept of health literacy and its assessment and the evidence of
      its impact on patients with diabetes, and offers suggested methods and tools that
      may be implemented to improve clinical care.

PMID- 21860660
TI  - Young smokers' views of genetic susceptibility testing for lung cancer risk:
      minding unintended consequences.
AB  - Assessment of smokers' responses to individualized feedback of genetic
      susceptibility has shown little or no influence on smoking cessation outcomes.
      One explanation is that smokers may be having unintended responses that undermine
      the feedback's motivational impact (e.g., fatalism or downplaying risk). In
      preparation for a large randomized trial with college smokers, we conducted a
      qualitative pilot study to explore smokers' motives for genetic testing and how
      these motives might influence interpretation of genetic risk feedback.Prior to
      reviewing informational materials describing a test for the glutathione S
      transferase M1 gene, 33 college smokers (18 to 21 years) participated in a 30
      minute, semi-structured, open-ended interview regarding their attitudes on health
      risks, genetic testing in general, genetic testing for lung cancer risk, and
      informational needs regarding genetics and genetic testing for lung cancer
      risk.Two central themes emerged from analysis of the interviews: general
      impressions of genetic testing and perceived value of genetic testing. Prominent
      in the second theme was the finding that genetic risk feedback may be
      unsuccessful in motivating quitting a) due to skepticism about genetic tests, b)
      participants dismissing genetic feedback as personally irrelevant, and c)
      participants receiving low risk results justifying continued smoking in light of
      public health messages that "it's never too late to quit". These findings require
      careful consideration among health professionals looking to genetic risk feedback
      as a vehicle to motivate disease prevention or behavior change.

PMID- 21860661
TI  - Comparing climate change and species invasions as drivers of coldwater fish
      population extirpations.
AB  - Species are influenced by multiple environmental stressors acting simultaneously.
      Our objective was to compare the expected effects of climate change and invasion
      of non-indigenous rainbow smelt (Osmerus mordax) on cisco (Coregonus artedii)
      population extirpations at a regional level. We assembled a database of over
      13,000 lakes in Wisconsin, USA, summarising fish occurrence, lake morphology,
      water chemistry, and climate. We used A1, A2, and B1 scenarios from the
      Intergovernmental Panel on Climate Change (IPCC) of future temperature conditions
      for 15 general circulation models in 2046-2065 and 2081-2100 totalling 78
      projections. Logistic regression indicated that cisco tended to occur in cooler,
      larger, and deeper lakes. Depending upon the amount of warming, 25-70% of cisco
      populations are predicted to be extirpated by 2100. In addition, cisco are
      influenced by the invasion of rainbow smelt, which prey on young cisco.
      Projecting current estimates of rainbow smelt spread and impact into the future
      will result in the extirpation of about 1% of cisco populations by 2100 in
      Wisconsin. Overall, the effect of climate change is expected to overshadow that
      of species invasion as a driver of coldwater fish population extirpations. Our
      results highlight the potentially dominant role of climate change as a driver of
      biotic change.

PMID- 21860662
TI  - Natural splice variant of MHC class I cytoplasmic tail enhances dendritic cell
      induced CD8+ T-cell responses and boosts anti-tumor immunity.
AB  - Dendritic cell (DC)-mediated presentation of MHC class I (MHC-I)/peptide
      complexes is a crucial first step in the priming of CTL responses, and the
      cytoplasmic tail of MHC-I plays an important role in modulating this process.
      Several species express a splice variant of the MHC-I tail that deletes exon 7
      encoding amino acids (Delta7), including a conserved serine phosphorylation site.
      Previously, it has been shown that Delta7 MHC-I molecules demonstrate extended DC
      surface half-lives, and that mice expressing Delta7-K(b) generate significantly
      augmented CTL responses to viral challenge. Herein, we show that Delta7-D(b)
      expressing DCs stimulated significantly more proliferation and much higher
      cytokine secretion by melanoma antigen-specific (Pmel-1) T cells. Moreover, in
      combination with adoptive Pmel-1 T-cell transfer, Delta7-D(b) DCs were superior
      to WT-D(b) DCs at stimulating anti-tumor responses against established B16
      melanoma tumors, significantly extending mouse survival. Human DCs engineered to
      express Delta7-HLA-A*0201 showed similarly enhanced CTL stimulatory capacity.
      Further studies demonstrated impaired lateral membrane movement and clustering of
      human Delta7-MHC-I/peptide complexes, resulting in significantly increased
      bioavailability of MHC-I/peptide complexes for specific CD8+ T cells.
      Collectively, these data suggest that targeting exon 7-encoded MHC-I cytoplasmic
      determinants in DC vaccines has the potential to increase CD8+ T-cell stimulatory
      capacity and substantially improve their clinical efficacy.

PMID- 21860663
TI  - Anatomical specializations for nocturnality in a critically endangered parrot,
      the Kakapo (Strigops habroptilus).
AB  - The shift from a diurnal to nocturnal lifestyle in vertebrates is generally
      associated with either enhanced visual sensitivity or a decreased reliance on
      vision. Within birds, most studies have focused on differences in the visual
      system across all birds with respect to nocturnality-diurnality. The critically
      endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an
      example of a species that has evolved a nocturnal lifestyle in an otherwise
      diurnal lineage, but nothing is known about its' visual system. Here, we provide
      a detailed morphological analysis of the orbits, brain, eye, and retina of the
      Kakapo and comparisons with other birds. Morphometric analyses revealed that the
      Kakapo's orbits are significantly more convergent than other parrots, suggesting
      an increased binocular overlap in the visual field. The Kakapo exhibits an eye
      shape that is consistent with other nocturnal birds, including owls and
      nightjars, but is also within the range of the diurnal parrots. With respect to
      the brain, the Kakapo has a significantly smaller optic nerve and tectofugal
      visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium
      were significantly reduced in relative size compared to other parrots. There was
      no apparent reduction to the thalamofugal visual pathway. Finally, the retinal
      morphology of the Kakapo is similar to that of both diurnal and nocturnal birds,
      suggesting a retina that is specialised for a crepuscular niche. Overall, this
      suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a
      larger binocular field than other parrots. We conclude that the Kakapo possesses
      a visual system unlike that of either strictly nocturnal or diurnal birds and
      therefore does not adhere to the traditional view of the evolution of
      nocturnality in birds.

PMID- 21860664
TI  - Tetracysteine-based fluorescent tags to study protein localization and
      trafficking in Plasmodium falciparum-infected erythrocytes.
AB  - Plasmodium falciparum (Pf) malaria parasites remodel host erythrocytes by placing
      membranous structures in the host cell cytoplasm and inserting proteins into the
      surrounding erythrocyte membranes. Dynamic imaging techniques with high spatial
      and temporal resolutions are required to study the trafficking pathways of
      proteins and the time courses of their delivery to the host erythrocyte membrane.
      METHODOLOGY AND FINDINGS: Using a tetracysteine (TC) motif tag and TC-binding
      biarsenical fluorophores (BAFs) including fluorescein arsenical hairpin (FlAsH)
      and resorufin arsenical hairpin (ReAsH), we detected knob-associated histidine
      rich protein (KAHRP) constructs in Pf-parasitized erythrocytes and compared their
      fluorescence signals to those of GFP (green fluorescent protein)-tagged KAHRP.
      Rigorous treatment with BAL (2, 3 dimercaptopropanol; British anti-Lewisite) was
      required to reduce high background due to nonspecific BAF interactions with
      endogenous cysteine-rich proteins. After this background reduction, similar
      patterns of fluorescence were obtained from the TC- and GFP-tagged proteins. The
      fluorescence from FlAsH and ReAsH-labeled protein bleached at faster rates than
      the fluorescence from GFP-labeled protein. CONCLUSION: While TC/BAF labeling to
      Pf-infected erythrocytes is presently limited by high background signals, it may
      offer a useful complement or alternative to GFP labeling methods. Our
      observations are in agreement with the currently-accepted model of KAHRP movement
      through the cytoplasm, including transient association of KAHRP with Maurer's
      clefts before its incorporation into knobs in the host erythrocyte membrane.

PMID- 21860665
TI  - Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features,
      and molecular characteristics.
AB  - INTRODUCTION: Circulating strains of Staphylococcus aureus (SA) have changed in
      the last 30 years including the emergence of community-associated methicillin
      resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS)
      was increasing over 2000-2003. The last population-based assessment of TSS was
      1986. METHODS: Population-based active surveillance for TSS meeting the CDC
      definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area
      (population 2,642,056) from 2000-2006. Medical records of potential cases were
      reviewed for case criteria, antimicrobial susceptibility, risk factors, and
      outcome. Superantigen PCR testing and PFGE were performed on available isolates
      from probable and confirmed cases. RESULTS: Of 7,491 hospitalizations that
      received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non
      menstrual) were identified. The average annual incidence per 100,000 of all,
      menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32-0.77), 0.69 (0.39-1.16),
      and 0.32 (0.12-0.67), respectively. Women 13-24 years had the highest incidence
      at 1.41 (0.63-2.61). No increase in incidence was observed from 2000-2006. MRSA
      was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1
      isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of
      isolates and was more common in menstrual compared to non-menstrual isolates (89%
      vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more
      frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p =
      0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively]. DISCUSSION:
      TSS incidence remained stable across our surveillance period of 2000-2006 and
      compared to past population-based estimates in the 1980s. MRSA accounted for a
      small percentage of TSS cases. tst-1 continues to be the superantigen associated
      with the majority of menstrual cases. The CDC case definition identifies the most
      severe cases and has been consistently used but likely results in a substantial
      underestimation of the total TSS disease burden.

PMID- 21860666
TI  - Effect of carbonate chemistry alteration on the early embryonic development of
      the Pacific oyster (Crassostrea gigas).
AB  - Ocean acidification, due to anthropogenic CO2 absorption by the ocean, may have
      profound impacts on marine biota. Calcareous organisms are expected to be
      particularly sensitive due to the decreasing availability of carbonate ions
      driven by decreasing pH levels. Recently, some studies focused on the early life
      stages of mollusks that are supposedly more sensitive to environmental
      disturbances than adult stages. Although these studies have shown decreased
      growth rates and increased proportions of abnormal development under low pH
      conditions, they did not allow attribution to pH induced changes in physiology or
      changes due to a decrease in aragonite saturation state. This study aims to
      assess the impact of several carbonate-system perturbations on the growth of
      Pacific oyster (Crassostrea gigas) larvae during the first 3 days of development
      (until shelled D-veliger larvae). Seawater with five different chemistries was
      obtained by separately manipulating pH, total alkalinity and aragonite saturation
      state (calcium addition). Results showed that the developmental success and
      growth rates were not directly affected by changes in pH or aragonite saturation
      state but were highly correlated with the availability of carbonate ions. In
      contrast to previous studies, both developmental success into viable D-shaped
      larvae and growth rates were not significantly altered as long as carbonate ion
      concentrations were above aragonite saturation levels, but they strongly
      decreased below saturation levels. These results suggest that the mechanisms used
      by these organisms to regulate calcification rates are not efficient enough to
      compensate for the low availability of carbonate ions under corrosive conditions.

PMID- 21860667
TI  - Global gradients of coral exposure to environmental stresses and implications for
      local management.
AB  - BACKGROUND: The decline of coral reefs globally underscores the need for a
      spatial assessment of their exposure to multiple environmental stressors to
      estimate vulnerability and evaluate potential counter-measures.
      METHODOLOGY/PRINCIPAL FINDINGS: This study combined global spatial gradients of
      coral exposure to radiation stress factors (temperature, UV light and doldrums),
      stress-reinforcing factors (sedimentation and eutrophication), and stress
      reducing factors (temperature variability and tidal amplitude) to produce a
      global map of coral exposure and identify areas where exposure depends on factors
      that can be locally managed. A systems analytical approach was used to define
      interactions between radiation stress variables, stress reinforcing variables and
      stress reducing variables. Fuzzy logic and spatial ordinations were employed to
      quantify coral exposure to these stressors. Globally, corals are exposed to
      radiation and reinforcing stress, albeit with high spatial variability within
      regions. Based on ordination of exposure grades, regions group into two clusters.
      The first cluster was composed of severely exposed regions with high radiation
      and low reducing stress scores (South East Asia, Micronesia, Eastern Pacific and
      the central Indian Ocean) or alternatively high reinforcing stress scores (the
      Middle East and the Western Australia). The second cluster was composed of
      moderately to highly exposed regions with moderate to high scores in both
      radiation and reducing factors (Caribbean, Great Barrier Reef (GBR), Central
      Pacific, Polynesia and the western Indian Ocean) where the GBR was strongly
      associated with reinforcing stress. CONCLUSIONS/SIGNIFICANCE: Despite radiation
      stress being the most dominant stressor, the exposure of coral reefs could be
      reduced by locally managing chronic human impacts that act to reinforce radiation
      stress. Future research and management efforts should focus on incorporating the
      factors that mitigate the effect of coral stressors until long-term carbon
      reductions are achieved through global negotiations.

PMID- 21860668
TI  - Prediction of ligand binding using an approach designed to accommodate diversity
      in protein-ligand interactions.
AB  - Computational determination of protein-ligand interaction potential is important
      for many biological applications including virtual screening for therapeutic
      drugs. The novel internal consensus scoring strategy is an empirical approach
      with an extended set of 9 binding terms combined with a neural network capable of
      analysis of diverse complexes. Like conventional consensus methods, internal
      consensus is capable of maintaining multiple distinct representations of protein
      ligand interactions. In a typical use the method was trained using ligand
      classification data (binding/no binding) for a single receptor. The internal
      consensus analyses successfully distinguished protein-ligand complexes from
      decoys (r2, 0.895 for a series of typical proteins). Results are superior to
      other tested empirical methods. In virtual screening experiments, internal
      consensus analyses provide consistent enrichment as determined by ROC-AUC and
      pROC metrics.

PMID- 21860669
TI  - Rectification of the current in alpha-hemolysin pore depends on the cation type:
      the alkali series probed by MD simulations and experiments.
AB  - A striking feature of the alpha-hemolysin channel-a prime candidate for
      biotechnological applications-is the dependence of its ionic conductance on the
      magnitude and direction of the applied bias. Through a combination of lipid
      bilayer single-channel recording and molecular dynamics (MD) simulations, we
      characterized the current-voltage relationship of alpha-hemolysin for all alkali
      chloride salts at neutral pH. The rectification of the ionic current was found to
      depend on the type of cations and increase from Li(+) to Cs(+). Analysis of the
      MD trajectories yielded a simple quantitative model that related the ionic
      current to the electrostatic potential, the concentration and effective mobility
      of ions in the channel. MD simulations reveal that the major contribution to the
      current asymmetry and rectification properties originates from the cationic
      contribution to the current that is significantly reduced in a cationic dependent
      way when the membrane polarity is reversed. The variation of chloride current was
      found to be less important. We report that the differential affinity of cations
      for the charged residues positioned at the channel's end modulates the number of
      ions inside the channel stem thus affecting the current properties. Through
      direct comparison of simulation and experiment, this study evaluates the accuracy
      of the MD method for prediction of the asymmetric, voltage dependent conductances
      of a membrane channel.

PMID- 21860670
TI  - Short and long term fate of human AMSC subcutaneously injected in mice.
AB  - AIM: To study the ability of human adipose-derived mesenchymal stem cells (AMSCs)
      to survive over the short and long term, their biodistribution and their
      biosafety in vivo in tumor-prone environments. METHODS: We subcutaneously
      injected human AMSCs from different human donors into immunodeficient SCID mice
      over both short- (2 and 4 mo) and long- (17 mo) term in young, and aged tumor
      prone mice. Presence of human cells was studied by immunohistochemistry and
      polymerase chain reaction analysis in all organs of injected mice. RESULTS:
      Subcutaneously injected AMSCs did not form teratomas at any time point. They did
      not migrate but remained at the site of injection regardless of animal age, and
      did not fuse with host cells in any organ examined. AMSCs survived in vivo for at
      least 17 mo after injection, and differentiated into fibroblasts of the subdermic
      connective tissue and into mature adipocytes of fat tissue, exclusively at the
      site of injection. CONCLUSION: Our results support the assertion that AMSC may be
      safe candidates for therapy when injected subcutaneously because of their long
      term inability to form teratomas.

PMID- 21860671
TI  - Identification of circulating CD90 CD73 cells in cirrhosis of liver.
AB  - AIM: To identify circulating CD90(+) CD73(+) CD45(-) cells and evaluate their in
      vitro proliferating abilities. METHODS: Patients with cirrhosis (n = 43), and
      healthy volunteers (n = 40) were recruited to the study. Mononuclear cells were
      isolated and cultured from the peripheral blood of controls and cirrhosis
      patients. Fibroblast-like cells that appeared in cultures were analyzed for
      morphological features, enumerated by flow cytometry and confirmed by
      immunocytochemistry (ICC). Colony forming efficiency (CFE) of these cells was
      assessed and expressed as a percentage. RESULTS: In comparison to healthy
      volunteers, cells obtained from cirrhotic patients showed a significant increase
      (P < 0.001) in the percentage of CD90(+) CD73(+) CD45(-) cells in culture.
      Cultured cells also showed 10 fold increases in CFE. Flow cytometry and ICC
      confirmed that the proliferating cells expressed CD90(+) CD73(+) in the cultures
      from cirrhosis patients. CONCLUSION: These results indicate the presence of
      circulating CD90(+) CD73(+) CD45(-) cells in patients with liver cirrhosis that
      have the potential to proliferate at a higher rate.

PMID- 21860672
TI  - Management of primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with
      major morbidity and mortality. Therapeutic management is difficult, due to lack
      of conclusive data and individual disease progression. High-dose UDCA was used
      for years as a pharmacotherapeutic agent to prevent disease progression, based on
      a positive trend in pilot studies, but has recently been proven to have a
      negative effect in advanced disease. Immunosuppressants might be useful in
      patients with overlap syndromes. Dominant bile duct stenoses should be treated
      endoscopically, and cholangiocellular carcinoma (CCC) still remains a therapeutic
      challenge in PSC patients. Early diagnosis of CCC must be improved and new
      strategies such as neoadjuvant radiochemotherapy with subsequent liver
      transplantation in selected patients are further options to be considered.

PMID- 21860673
TI  - A key problem and challenge for hepatology: Obesity-related metabolic liver
      diseases.
AB  - With the arrival of the new millennium, gastroenterologists have been faced with
      the problem of metabolic liver diseases associated with obesity. The active role
      of the liver in metabolism and inflammation make it a key organ in the war
      against the rapidly-spreading world-wide epidemic of obesity. Many lives and much
      money could be saved if the work of hepatologists led to the development of
      effective diagnostic and therapeutic strategies against this growing leader of
      cirrhosis.

PMID- 21860674
TI  - HBV vaccine efficacy and detection and genotyping of vaccinee asymptomatic
      breakthrough HBV infection in Egypt.
AB  - AIM: To evaluate the impact of mass vaccination against the hepatitis B virus
      (HBV) in Egypt, and to search for vaccinee asymptomatic breakthrough HBV
      infection and its genotype. METHODS: Seven hundred serum samples from vaccinated
      children and adults (aged 2-47 years) were used for quantitative and qualitative
      detection of HBsAb by ELISA. Three hundred and sixty serum samples representing
      undetectable or low or high HBsAb were screened for markers of active HBV
      infection (HBsAg, HBcAb (IgG) and HBeAb by ELISA, plus HBsAg by AxSYM) and HBV
      DNA genotyping by nested multiplex PCR and by DNA sequencing. RESULTS: It was
      found that 65% of children aged 2-4 years, and 20.5% aged 4-13 years, as well as
      45% adults were good responders to HBV vaccination mounting protective level
      HBsAb. Poor responders were 28%, 59.5% and 34%, and non-responders were 7%, 20%
      and 21% respectively, in the three studied groups. Markers of asymptomatic HBV
      infections were HBsAg detected by ELISA in 2.5% vs 11.39% by AxSYM. Other markers
      were HBcAb (IgG) in 1.38%, HBeAb in 0.83%, and HBV-DNA in 7.8%. All had HBV
      genotype E infection. CONCLUSION: It is concluded that HBV vaccine is efficient
      in controlling HBV infection among children and adults. The vaccine breakthrough
      infection was by HBV genotype E. A booster dose of vaccine is recommended,
      probably four years after initial vaccination.

PMID- 21860675
TI  - MELD score, insulin-like growth factor 1 and cytokines on bone density in end
      stage liver disease.
AB  - AIM: To determine the contributions of insulin-like growth factor 1 (IGF-1),
      cytokines and liver disease severity to bone mineral density in patients pre
      transplantation. METHODS: Serum IGF-1, tumor necrosis factor-alpha (TNFalpha) and
      interleukin 6 (IL-6) were measured and the Model for End-Stage Liver Disease
      (MELD) score calculated in 121 adult patients referred to a single centre for
      liver transplantation. Bone mineral density (BMD) of the lumbar spine and femoral
      neck were assessed via dual energy X-ray absorptiometry. Demographics, liver
      disease etiology, medication use and relevant biochemistry were recorded.
      RESULTS: A total of 117 subjects were included, with low BMD seen in 68.6%,
      irrespective of disease etiology. In multivariable analysis, low body mass index
      (BMI), increased bone turnover and low IGF-1 were independent predictors of low
      spinal bone density. At the hip, BMI, IGF-1 and vitamin D status were predictive.
      Despite prevalent elevations of TNFalpha and IL-6, levels did not correlate with
      degree of bone loss. The MELD score failed to predict low BMD in this pre
      transplant population. CONCLUSION: Osteopenia/osteoporosis is common in advanced
      liver disease. Low serum IGF-1 is weakly predictive but serum cytokine and MELD
      score fail to predict the severity of bone disease.

PMID- 21860676
TI  - Budd-Chiari syndrome in a patient with ulcerative colitis and no inherited
      coagulopathy.
AB  - We report a case of 27 year old female patient who was admitted to the hospital
      with an acute flare up of ulcerative colitis. The patient presented with
      complaints of persistent abdominal pain and bloody diarrhea despite aggressive
      therapy for her ulcerative colitis. A CT scan of the abdomen on admission
      revealed hepatic vein thrombosis, suggesting a diagnosis of Budd-Chiari syndrome.
      Significantly, an associated thrombosis of the inferior mesenteric vein was also
      detected. Based on imaging data and clinical assessment, the patient was started
      on anticoagulation therapy and an extensive work-up for hypercoagulability was
      initiated. Up to the time of publication, no significant findings suggesting this
      patient has an underlying coagulation disorder have been found. Based on our
      search of PUBMED, this report is one of only five reported adult cases of Budd
      Chiari Syndrome associated with ulcerative colitis in the English literature in
      living patients without evidence of a co-existing coagulation disorder. This case
      highlights the potential for thrombosis at unusual sites in ulcerative colitis
      patients even in the absence of classical coagulation abnormalities. In addition
      to the case presented, we provide a brief review of previously reported cases of
      Budd-Chiari Syndrome occurring in patients with inflammatory bowel disease.

PMID- 21860677
TI  - Transumbilical endoscopic surgery: History, present situation and perspectives.
AB  - Transumbilical endoscopic surgery or laparo-endoscopic single site (LESS) surgery
      has become an exciting area of surgical development as innovation continues to
      move in the 21(st) century to minimally invasive surgery. The history, present
      situation and perspectives are reviewed and the nomenclature of this technique is
      discussed in this article. The range of this technique has been applied in almost
      all abdominal diseases, surgeries for morbid obesity, hernia and so on, in recent
      years. It is estimated that 50%-80% of traditional laparoscopic surgery could be
      performed transumbilically in the next five years according to the LESSCAR
      consensus. Although the concept of transumbilical laparoscopic surgery is gaining
      traction rapidly and the instruments have been improved greatly, we should not
      advocate for slightly improved cosmetic value over safety. Multicenter,
      randomized and clinical trials are necessary to further elucidate the safety and
      efficiency of this new technique. Research that examines the efficacy of the new
      instruments on the market may be helpful to simplify the confusing landscape of
      new and novel products designed for this purpose.

PMID- 21860678
TI  - Abdominal hernias: Radiological features.
AB  - Abdominal wall hernias are common diseases of the abdomen with a global incidence
      approximately 4%-5%. They are distinguished in external, diaphragmatic and
      internal hernias on the basis of their localisation. Groin hernias are the most
      common with a prevalence of 75%, followed by femoral (15%) and umbilical (8%).
      There is a higher prevalence in males (M:F, 8:1). Diagnosis is usually made on
      physical examination. However, clinical diagnosis may be difficult, especially in
      patients with obesity, pain or abdominal wall scarring. In these cases, abdominal
      imaging may be the first clue to the correct diagnosis and to confirm suspected
      complications. Different imaging modalities are used: conventional radiographs or
      barium studies, ultrasonography and Computed Tomography. Imaging modalities can
      aid in the differential diagnosis of palpable abdominal wall masses and can help
      to define hernial contents such as fatty tissue, bowel, other organs or fluid.
      This work focuses on the main radiological findings of abdominal herniations.

PMID- 21860679
TI  - Regular arrangement of collecting venules: Does patient age affect its accuracy?
AB  - AIM: To address the diagnostic value of the regular arrangement of collecting
      venules (RAC) among old age patients. METHODS: A total of 390 consecutive
      patients whose Helicobacter pylori (H. pylori) status was known and who received
      upper gastrointestinal endoscopy, were retrospectively studied for the presence
      or absence of RAC as well as gastric mucosal atrophy. The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      RAC to detect normal gastric mucosa were assessed and were compared among two
      different age groups of patients. RESULTS: The mean age +/- standard deviation
      (SD) of included patients (n = 390), was 62.9 +/- 13 years. The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      RAC to detect normal gastric mucosa were 91.7%, 66.1%, 18.8%, 99% and 68.1%
      respectively. Although the sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy of RAC among patients < 60 years (n = 139)
      was 94.7%, 71.2%, 46.2%, 98.1%and 76.1%, respectively, it was 80%, 64.3%, 5.1%,
      93% and 64.6%, respectively, among patients >= 60 years (n = 251). Younger
      Patients (< 60 years), have highly significant rates of RAC sensitivity, positive
      predictive value, and accuracy (P <= 0.001, <= 0.001 and <= 0.02, respectively).
      Older patients had highly significant rates of H. pylori infection and gastric
      mucosal atrophy (P <= 0.01). CONCLUSION: Although RAC is a valuable sign for real
      time identification of normal gastric mucosa, its accuracy seems to be affected
      by the patient's age.

PMID- 21860680
TI  - Endoscopic ultrasound with biopsy of omental mass for cholangiocarcinoma
      diagnosis in cirrhosis.
AB  - In this report, a patient had a previous diagnosis of cholangiocarcinoma with an
      extended cholecystectomy. Three years later, he was evaluated for recurrent
      ascites. The patient had several large volume paracentesis, without evidence of
      malignant cells. Subsequently, endoscopic ultrasound (EUS) with fine needle
      aspiration (FNA) of both lymph and omental nodules was utilized. While the lymph
      nodes were negative for malignancy, the omental nodule was interrogated with
      multiple antibodies and was found to be positive for neoplasia. EUS with FNA can
      safely be used in patients with cirrhosis to spare the patient invasive
      evaluation such as exploratory laparotomy (ex-lap) for diagnosis and staging of
      cholangiocarcinoma.

PMID- 21860681
TI  - Successful endoscopic resolution of a large gastric bezoar in a child.
AB  - Bezoars are masses or concretions of indigestible materials found in the
      gastrointestinal tract, usually in the stomach. Case reports of childhood gastric
      bezoars (particularly phytobezoars) are rare. In this age group they represent a
      therapeutic challenge, because of the combination of hard consistency and great
      size. The present report concerns an 8-year-old boy with a history of high fruit
      intake, presenting with abdominal complaints due to a large gastric phytobezoar.
      Successful endoscopic fragmentation coupled with suction removal was
      accomplished, using a standard-channel endoscope. Although laborious, it has been
      shown to be an efficacious and safe procedure, completed in one session.
      Endoscopic techniques for pediatric bezoar management may thus be cost effective,
      taking into account the avoidance of surgery, the length of the hospital stay and
      the number of endoscopic sessions.

PMID- 21860682
TI  - Management of early gastrointestinal neuroendocrine neoplasms.
AB  - Neuroendocrine neoplasms (NENs) of the stomach, duodenum, appendix or rectum that
      are small (<= 1 cm) and well differentiated can be considered "early" tumors,
      since they generally have a (very) good prognosis. In the new WHO classification
      of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs),
      grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine
      carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted
      incidence in the U.S.A. by about 700 % in the last 35 years. Improved early
      detection seems to be the main reason for these epidemiological changes. Both the
      better general availability of endoscopy, and imaging techniques, have led to a
      shift in the discovery of smaller-sized (<= 10-20 mm) intestinal NETs/carcinoids
      and earlier tumor stages at diagnosis. Endoscopic screening is therefore
      effective in the early diagnosis, not only of colorectal adenocarcinomas, but
      also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic
      surveillance is the treatment of choice in NETs/carcinoids of the stomach,
      duodenum and rectum that are <= 10 mm in size, have a low proliferative activity
      (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the
      other intestinal NENs, optimal treatment generally needs surgery and/or medical
      therapy depending on type, biology and stage of the tumor, as well as the
      individual situation of the patient.

PMID- 21860683
TI  - Radiation dose to patients during endoscopic retrograde cholangiopancreatography.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool for
      the diagnosis and treatment of the hepatobiliary system. The use of fluoroscopy
      to aid ERCP places both the patient and the endoscopy staff at risk of radiation
      induced injury. Radiation dose to patients during ERCP depends on many factors,
      and the endoscopist cannot control some variables, such as patient size,
      procedure type, or fluoroscopic equipment used. Previous reports have
      demonstrated a linear relationship between radiation dose and fluoroscopy
      duration. When fluoroscopy is used to assist ERCP, the shortest fluoroscopy time
      possible is recommended. Pulsed fluoroscopy and monitoring the length of
      fluoroscopy have been suggested for an overall reduction in both radiation
      exposure and fluoroscopy times. Fluoroscopy time is shorter when ERCP is
      performed by an endoscopist who has many years experience of performing ERCP and
      carried out a large number of ERCPs in the preceding year. In general, radiation
      exposure is greater during therapeutic ERCP than during diagnostic ERCP. Factors
      associated with prolonged fluoroscopy have been delineated recently, but these
      have not been validated.

PMID- 21860684
TI  - Development of a novel endoscopic manipulation system: The Endoscopic operation
      robot.
AB  - AIM: To develop and evaluate the endoscopic operation robot (EOR). The EOR is a
      robot system designed specifically for remote manipulation of the scope during
      gastrointestinal endoscopy by a seated endoscopist. METHODS: Total colonoscopy
      examinations using a colonoscopy training model were performed compared
      conventional insertion by manual manipulation and remote-controlled insertion,
      using the EOR. The author investigated the time taken for each of the 50
      examinations. RESULTS: The median insertion time (in minutes) for each 10
      examinations (EOR vs manual manipulation) was 73.70 +/- 25.37 vs 3.77 +/- 1.34 in
      the first group, 38.40 +/- 6.24 vs 3.40 +/- 0.97 in the second group, 27.6 +/-
      4.01 vs 2.70 +/- 0.95 in the third group, 23.8 +/- 3.65 vs 3.10 +/- 0.88 in the
      fourth group, and 22.9 +/- 5.02 vs 2.60 +/- 1.08 in the fifth group. CONCLUSION:
      The study suggested the possibility of the clinical application of the EOR.

PMID- 21860685
TI  - Endoscopic hemostasis for hemorrhage from an ileal diverticulum.
AB  - Hemorrhage from a non-Meckelian jejunoileal diverticulum is rare, and it is
      generally difficult to diagnose the source of the bleeding. Here, we report the
      case of a 59-year-old male with hemorrhage from an ileal diverticulum. Contrast
      computed tomography scans demonstrated the ileal diverticulum and extravasation
      of the contrast medium around it. The diagnosis was then made by computed
      tomography scans, and endoscopic mechanical hemostasis was performed under
      colonoscopy with three metal clips. The management of hemorrhage from jejunoileal
      diverticula is discussed.

PMID- 21860686
TI  - Complete clinical response of liver metastasis after chemotherapy: To resect or
      not?
AB  - This paper aims to update the therapeutical strategies in liver metastasis with
      complete clinical response (CCR) after chemotherapy and to determine if surgery
      is always necessary after CCR. The aim of chemotherapy is to achieve a good
      clinical response rather than CCR of liver metastasis. The CCR of liver
      metastasis after chemotherapy cannot be considered synonymous with a cure. The
      resection of the hepatic segment where there was hepatic metastases with CCR
      after chemotherapy theoretically prevents recurrence, improves survival and makes
      it possible to confirm whether there has been a complete pathological response.
      However, the medical literature about this topic is scarce and sometimes
      contradictory.

PMID- 21860687
TI  - Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the
      inferior common bile duct.
AB  - A carcinoma displaying undifferentiated features with dense lymphoplasmacytic
      infiltration is defined as a lymphoepithelioma-like carcinoma (LEC), and some of
      LEC is associated with Epstein-Barr virus (EBV). All of the 13 previously
      reported cases of LEC of the biliary system were intrahepatic in location.
      Herein, we describe the first case of LEC of the inferior common bile duct. A 68
      year-old Japanese man, who had been previously treated for hepatocellular
      carcinoma using microwave coagulation therapy, was found to have tumors of the
      common bile duct and pancreas head. Histopathological study of the resected tumor
      showed solid or cohesive nests of large undifferentiated cells with irregular
      large vesicular nuclei and nucleoli. Around the tumor cell nests, dense
      lymphoplasmacytic infiltration was observed. Focal glandular differentiation
      (approximately 5%) was also present. These histopathological features
      corresponded morphologically to LEC. Immunohistochemically, the tumor cells were
      positive for cytokeratin (CK) 7, CK 19 and CA19-9, but negative for CK 20 and Hep
      Par 1. In situ hybridization for Epstein Barr virus early small RNAs disclosed no
      nuclear signal in tumor cells. Therefore, a diagnosis of non-EBV-associated LEC
      of the inferior common bile duct was made. Although the prognosis of the biliary
      LEC is thought to be better than that of conventional cholangiocarcinoma, the
      differences in prognosis between EBV-positive and -negative cases have not yet
      been established. Therefore, additional case studies will be needed to clarify
      the clinicopathological features of LEC of the biliary tract.

PMID- 21860688
TI  - Dedifferentiated liposarcoma of the small bowel mesentery presenting as a
      submucosal mass.
AB  - Dedifferentiated liposarcoma (DDLPS) is a variant of liposarcoma but with a more
      aggressive course. It occurs most commonly in the retroperitoneum and rarely in
      any other anatomical location. We describe a case of DDLPS arising from the small
      bowel mesentery presenting as submucosal mass of the small bowel. The current
      case is unusual as the tumor originated from the small bowel mesentery and a
      dedifferentiated component transmurally invaded the small bowel wall, including
      the small bowel submucosa.

PMID- 21860689
TI  - Fluid Flow and Effusive Desorption: Dominant Mechanisms of Energy Dissipation
      after Energetic Cluster Bombardment of Molecular Solids.
AB  - The angular distribution of intact organic molecules desorbed by energetic C(60)
      primary ions was probed both experimentally and with molecular dynamics computer
      simulations. For benzo[a]pyrene, the angular distribution of intact molecules is
      observed to peak at off-normal angles. Molecular dynamics computer simulations on
      a similar system show the mechanism of desorption involves fast deposition of
      energy followed by fluid-flow and effusive-type emission of intact molecules. The
      off-normal peak in the angular distribution is shown to arise from emission of
      intact molecules from the rim of a crater formed during the cluster impact. This
      signature is unique for molecules because fragmentation processes remove
      molecules that would otherwise eject at directions near-normal to the surface.

PMID- 21860690
TI  - High dietary fructose intake: Sweet or bitter life?
AB  - Epidemiological data show that the consumption of added sugars as ingredients in
      processed or prepared foods and caloric beverages has dramatically increased.
      Fructose and fructose-based sweeteners are the most commonly added sugars and
      high-fructose corn syrup (HFCS-55: 55% fructose, 42% glucose and 3% higher
      saccharides) accounts for over 40% of all added caloric sweeteners. Concerns
      regarding the health risk of added sugar follow the demonstration that the
      consumption of foods and beverages high in sugars is associated with an increased
      prevalence of obesity, insulin resistance, dyslipidemia and, more recently,
      ischemic heart and kidney diseases. The molecular mechanism(s) underlying the
      detrimental effects of sugar are not completely understood and their elucidation
      is critical to provide new insights on the health risk of fructose-based
      sweeteners. A better understanding of the key role of fructose overconsumption in
      the development of metabolic disorders may contribute to planning new strategies
      for preventing deleterious dietary behaviors from becoming established and, thus,
      curbing the rise in the number of insulin-resistant, obese and diabetic
      populations worldwide.

PMID- 21860692
TI  - Vascular dysfunction in diabetes: The endothelial progenitor cells as new
      therapeutic strategy.
AB  - The vascular endothelium is a critical determinant of diabetes-associated
      vascular complications, and improving endothelial function is an important target
      for therapy. Diabetes mellitus contributes to endothelial cell injury and
      dysfunction. Endothelial progenitor cells (EPCs) play a critical role in
      maintaining endothelial function and might affect the progression of vascular
      disease. EPCs are essential to blood vessel formation, can differentiate into
      mature endothelial cells, and promote the repair of damaged endothelium. In
      diabetes, the circulating EPC count is low and their functionality is impaired.
      The mechanisms that underlie this reduced count and impaired functionality are
      poorly understood. Knowledge of the status of EPCs is critical for assessing the
      health of the vascular system, and interventions that increase the number of EPCs
      and restore their angiogenic activity in diabetes may prove to be particularly
      beneficial. The present review outlines current thinking on EPCs' therapeutic
      potential in endothelial dysfunction in diabetes, as well as evidence-based
      perspectives regarding their use for vascular regenerative medicine.

PMID- 21860693
TI  - Managing diabetic macular edema: The leading cause of diabetes blindness.
AB  - Diabetic macular edema (DME) is the leading cause of blindness in young adults in
      developed countries, affecting 12% of type 1 and 28% of type 2 diabetic patients.
      The gold standard DME treatment should be based on a good control of glycemia
      along with control of lipids and renal function. However, despite the systemic
      metabolic control values being essential for patients with diabetic retinopathy
      (DR), it has proven to be insufficient for DME if it appears. With these
      patients, additional measures are needed in order to avoid the subsequent loss of
      vision. While laser treatment of DME has been the only valid treatment so far, it
      has been inadequate in chronic cases. The introduction of new treatments, such as
      intravitreal corticosteroids or anti-VEGF drugs, have recently shown their safety
      and efficacy and together with laser photocoagulation are becoming the treatments
      of choice in the management of DME.

PMID- 21860694
TI  - Complexity of drug therapy and its implications for quality of diabetes care.
AB  - Diabetes is a leading cause of mortality, morbidity and disability around the
      globe. In the past two decades, diabetes care has grown more complex as patients
      have received multi-component care. Recent studies have illumined the complexity
      of drug therapy in patients with diabetes. A high level of drug utilization in
      diabetes patients has serious implications for quality of care, in terms of
      coordination of care, drug safety and access to care. Practitioners, researchers,
      payers and policy makers should be aware of these implications and incorporate
      the complexity of diabetes care into practice guidelines, benefit design and
      policy formulation to improve the quality of care.

PMID- 21860691
TI  - Role of melatonin on diabetes-related metabolic disorders.
AB  - Melatonin is a circulating hormone that is mainly released from the pineal gland.
      It is best known as a regulator of seasonal and circadian rhythms, its levels
      being high during the night and low during the day. Interestingly, insulin levels
      are also adapted to day/night changes through melatonin-dependent
      synchronization. This regulation may be explained by the inhibiting action of
      melatonin on insulin release, which is transmitted through both the pertussis
      toxin-sensitive membrane receptors MT(1) and MT(2) and the second messengers
      3',5'-cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and
      inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated
      metabolic disturbances not only by regulating insulin secretion, but also by
      providing protection against reactive oxygen species, since pancreatic beta-cells
      are very susceptible to oxidative stress because they possess only low
      antioxidative capacity. On the other hand, in several genetic association
      studies, single nucleotide polymorphysms of the human MT(2) receptor have been
      described as being causally linked to an elevated risk of developing type 2
      diabetes. This suggests that these individuals may be more sensitive to the
      actions of melatonin, thereby leading to impaired insulin secretion. Therefore,
      blocking the melatonin-induced inhibition of insulin secretion may be a novel
      therapeutic avenue for type 2 diabetes.

PMID- 21860695
TI  - Diabetes and cancer: Looking at the multiligand/RAGE axis.
AB  - The association between diabetes and hyperglycemia and the associated increased
      risk of several solid and hematologic malignancies has been the subject of
      investigation for many years. Although the association is not fully understood,
      current knowledge clearly indicates that diabetes may influence malignant cell
      transformation by several mechanisms, including hyperinsulinemia, hyperglycemia
      and chronic inflammation. In this context, the receptor for advanced glycation
      end-products (RAGE) has emerged as a focal point in its contribution to malignant
      transformation and tumor growth. We highlight how RAGE, once activated, as it
      manifests itself in conditions such as diabetes or hyperglycemia, is able to
      continuously bring about an inflammatory milieu, thus supporting the contribution
      of chronic inflammation to the development of malignancies.

PMID- 21860696
TI  - Unravelling the story of protein misfolding in diabetes mellitus.
AB  - Both environmental and genetic factors contribute to the development of diabetes
      mellitus and although monogenic disorders are rare, they offer unique insights
      into the fundamental biology underlying the disease. Mutations of the insulin
      gene or genes involved in the response to protein misfolding cause early onset
      diabetes. These have revealed an important role for endoplasmic reticulum stress
      in beta-cell survival. This form of cellular stress occurs when secretory
      proteins fail to fold efficiently. Of all the professional secretory cells we
      possess, beta-cells are the most sensitive to endoplasmic reticulum stress
      because of the large fluctuations in protein synthesis they face daily. Studies
      of endoplasmic reticulum stress signaling therefore offer the potential to
      identify new drug targets to treat diabetes.

PMID- 21860697
TI  - Recent advances in endovascular techniques for management of acute nonvariceal
      upper gastrointestinal bleeding.
AB  - Over the past two decades, transcatheter arterial embolization has become the
      first-line therapy for the management of upper gastrointestinal bleeding that is
      refractory to endoscopic hemostasis. Advances in catheter-based techniques and
      newer embolic agents, as well as recognition of the effectiveness of minimally
      invasive treatment options, have expanded the role of interventional radiology in
      the management of hemorrhage for a variety of indications, such as peptic ulcer
      bleeding, malignant disease, hemorrhagic Dieulafoy lesions and iatrogenic or
      trauma bleeding. Transcatheter interventions include the following: selective
      embolization of the feeding artery, sandwich coil occlusion of the gastroduodenal
      artery, blind or empiric embolization of the supposed bleeding vessel based on
      endoscopic findings and coil pseudoaneurysm or aneurysm embolization by three
      dimensional sac packing with preservation of the parent artery. Transcatheter
      embolization is a fast, safe and effective, minimally invasive alternative to
      surgery when endoscopic treatment fails to control bleeding from the upper
      gastrointestinal tract. This article reviews the various transcatheter
      endovascular techniques and devices that are used in a variety of clinical
      scenarios for the management of hemorrhagic gastrointestinal emergencies.

PMID- 21860698
TI  - Laparoscopic liver resection for hepatocellular adenoma.
AB  - AIM: To investigate the role of laparoscopy in the surgical management of
      hepatocellular adenoma (HA). METHODS: We reviewed a prospectively collected
      database of consecutive patients undergoing laparoscopic liver resection for HA.
      RESULTS: Thirteen patients underwent fifteen pure laparoscopic liver resections
      for HA (male/female: 3/10; median age 42 years, range 22-72 years). Two patients
      with liver adenomatosis required two different laparoscopic operations for
      ruptured adenomas. Indications for surgery were: symptoms in 12 cases, need to
      rule out malignancy in 2 cases and preoperative diagnosis of large HA in one
      case. Symptoms were related to bleeding in 10 cases, sepsis due to liver abscess
      following embolization of HA in one case and mass effect in one case (shoulder
      tip pain). Five cases with ruptured bleeding adenoma required emergency admission
      and treatment with selective arterial embolization. Laparoscopic liver resection
      was then semi-electively performed. Eight patients (62%) required major
      hepatectomy [right hepatectomy (n = 5), left hepatectomy (n = 3)]. No conversion
      to open surgery occurred. The median operative time for pure laparoscopic
      procedures was 270 min (range 135-360 min). The median size of the excised
      lesions was 85 mm (range 25-180 mm). One patient with adenomatosis developed
      postoperative bleeding requiring embolization. Mortality was nil. The median
      hospital stay was 4 d (range 1-18 d) with a median high dependency unit stay of 1
      d (range 0-7 d). CONCLUSION: The laparoscopic approach represents a safe option
      for the management of HA in a semi-elective setting and when major hepatectomy is
      required.

PMID- 21860699
TI  - Intestinal obstruction caused by torsed gangrenous Meckel's diverticulum
      encircling terminal ileum.
AB  - Meckel's diverticulum (MD) is considered the most prevalent congenital anomaly of
      the gastrointestinal tract. It may result in a number of complications including
      hemorrhage, obstruction, and inflammation. Obstruction of various types is the
      most common presenting symptom in the adult population. Loop formations with the
      end of an MD and adjacent mesentery constricting the distal ileum is an uncommon
      cause of obstruction. Axial torsion and gangrene of MD is the rarest of the
      complications. The correct diagnosis of complicated MD before surgery is often
      difficult because this condition may mimic other acute abdominal pathologies.
      Delay in the diagnosis of a complicated MD can lead to significant morbidity and
      mortality. Here we describe the case of a patient with a very rare form of acute
      small bowel obstruction secondary to giant torsed gangrenous MD encircling the
      terminal ileum. To our knowledge, this co-occurrence of axial torsion and a loop
      forming mechanism of obstruction has been reported only once in English medical
      literature.

PMID- 21860700
TI  - Hepatic flow optimization in full right split liver transplantation.
AB  - Split liver transplantation for two adults offers a valuable opportunity to
      expand the donor pool for adult recipients. However, its application is mainly
      hampered by the physiological limits of these partial grafts. Small for size
      syndrome is a major concern during transplantation with partial graft and
      different techniques have been developed in living donor liver transplantation to
      prevent the graft dysfunction. Herein, we report the first application of
      synergic approaches to optimise the hepatic hemodynamic in a split liver graft
      for two adults. A Caucasian woman underwent liver transplantation for alcoholic
      cirrhosis (MELD 21) with a full right liver graft (S5-S8) without middle hepatic
      vein. Minor and accessory inferior hepatic veins were preserved by splitting the
      vena cava; V5 and V8 were anastomosed with a donor venous iliac patch. After
      implantation, a 16G catheter was advanced in the main portal trunk. Inflow
      modulation was achieved by splenic artery ligation. Intraportal infusion of PGE1
      was started intraoperatively and discontinued after 5 d. Graft function was
      immediate with normalization of liver test after 7 d. Nineteen months after
      transplantation, liver function is normal and graft volume is 110% of the
      recipient standard liver volume. Optimisation of the venous outflow, inflow
      modulation and intraportal infusion of PGE1 may represent a valuable synergic
      strategy to prevent the graft dysfunction and it may increase the safety of split
      liver graft for two adults.

PMID- 21860701
TI  - JUPITER and satellites: Clinical implications of the JUPITER study and its
      secondary analyses.
AB  - THE JUSTIFICATION FOR THE USE OF STATINS IN PREVENTION: an intervention trial
      evaluating rosuvastatin (JUPITER) study was a real breakthrough in primary
      cardiovascular disease prevention with statins, since it was conducted in
      apparently healthy individuals with normal levels of low-density lipoprotein
      cholesterol (LDL-C < 130 mg/dL) and increased inflammatory state, reflected by a
      high concentration of high-sensitivity C-reactive protein (hs-CRP >= 2 mg/L).
      These individuals would not have qualified for statin treatment according to
      current treatment guidelines. In JUPITER, rosuvastatin was associated with
      significant reductions in cardiovascular outcomes as well as in overall mortality
      compared with placebo. In this paper the most important secondary analyses of the
      JUPITER trial are discussed, by focusing on their novel findings regarding the
      role of statins in primary prevention. Also, the characteristics of otherwise
      healthy normocholesterolemic subjects who are anticipated to benefit more from
      statin treatment in the clinical setting are discussed. Subjects at
      "intermediate" or "high" 10-year risk according to the Framingham score, those
      who exhibit low post-treatment levels of both LDL-C (< 70 mg/dL) and hs-CRP (< 1
      mg/L), who are 70 years of age or older, as well as those with moderate chronic
      kidney disease (estimated glomerular filtration rate < 60 mL/min every 1.73 m(2))
      are anticipated to benefit more from statin treatment. Unlikely other statin
      primary prevention trials, JUPITER added to our knowledge that statins may be
      effective drugs in the primary prevention of cardiovascular disease in
      normocholesterolemic individuals at moderate-to-high risk. Also, statin treatment
      may reduce the risk of venous thromboembolism and preserve renal function. An
      increase in physician-reported diabetes represents a major safety concern
      associated with the use of the most potent statins.

PMID- 21860702
TI  - Calcium channels and iron uptake into the heart.
AB  - Iron overload can lead to iron deposits in many tissues, particularly in the
      heart. It has also been shown to be associated with elevated oxidative stress in
      tissues. Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,
      a condition which provokes mortality due to heart failure in iron-overloaded
      patients. Currently, the mechanism of iron uptake into cardiomyocytes is still
      not clearly understood. Growing evidence suggests L-type Ca(2+) channels (LTCCs)
      as a possible pathway for ferrous iron (Fe(2+)) uptake into cardiomyocytes under
      iron overload conditions. Nevertheless, controversy still exists since some
      findings on pharmacological interventions and those using different cell types do
      not support LTCC's role as a portal for iron uptake in cardiac cells. Recently, T
      type Ca(2+) channels (TTCC) have been shown to play an important role in the
      diseased heart. Although TTCC and iron uptake in cardiomyocytes has not been
      investigated greatly, a recent finding indicated that TTCC could be an important
      portal in thalassemic hearts. In this review, comprehensive findings collected
      from previous studies as well as a discussion of the controversy regarding iron
      uptake mechanisms into cardiomyocytes via calcium channels are presented with the
      hope that understanding the cellular iron uptake mechanism in cardiomyocytes will
      lead to improved treatment and prevention strategies, particularly in iron
      overloaded patients.

PMID- 21860703
TI  - Non-invasive detection of vulnerable coronary plaque.
AB  - Critical coronary stenoses have been shown to contribute to only a minority of
      acute coronary syndromes and sudden cardiac death. Autopsy studies have
      identified a subgroup of high-risk patients with disrupted vulnerable plaque and
      modest stenosis. Consequently, a clinical need exists to develop methods to
      identify these plaques prospectively before disruption and clinical expression of
      disease. Recent advances in invasive and non-invasive imaging techniques have
      shown the potential to identify these high-risk plaques. Non-invasive imaging
      with magnetic resonance imaging, computed tomography and positron emission
      tomography holds the potential to differentiate between low- and high-risk
      plaques. There have been significant technological advances in non-invasive
      imaging modalities, and the aim is to achieve a diagnostic sensitivity for these
      technologies similar to that of the invasive modalities. Molecular imaging with
      the use of novel targeted nanoparticles may help in detecting high-risk plaques
      that will ultimately cause acute myocardial infarction. Moreover, nanoparticle
      based imaging may even provide non-invasive treatments for these plaques.
      However, at present none of these imaging modalities are able to detect
      vulnerable plaque nor have they been shown to definitively predict outcome.
      Further trials are needed to provide more information regarding the natural
      history of high-risk but non-flow-limiting plaque to establish patient specific
      targeted therapy and to refine plaque stabilizing strategies in the future.

PMID- 21860704
TI  - Implications of discoveries from genome-wide association studies in current
      cardiovascular practice.
AB  - Genome-wide association studies (GWAS) have identified several genetic variants
      associated with coronary heart disease (CHD), and variations in plasma
      lipoproteins and blood pressure (BP). Loci corresponding to CDKN2A/CDKN2B/ANRIL,
      MTHFD1L, CELSR2, PSRC1 and SORT1 genes have been associated with CHD, and TMEM57,
      DOCK7, CELSR2, APOB, ABCG5, HMGCR, TRIB1, FADS2/S3, LDLR, NCAN and TOMM40-APOE
      with total cholesterol. Similarly, CELSR2-PSRC1-SORT1, PCSK9, APOB, HMGCR, NCAN
      CILP2-PBX4, LDLR, TOMM40-APOE, and APOC1-APOE are associated with variations in
      low-density lipoprotein cholesterol levels. Altogether, forty, forty three and
      twenty loci have been associated with high-density lipoprotein cholesterol,
      triglycerides and BP phenotypes, respectively. Some of these identified loci are
      common for all the traits, some do not map to functional genes, and some are
      located in genes that encode for proteins not previously known to be involved in
      the biological pathway of the trait. GWAS have been successful at identifying new
      and unexpected genetic loci common to diseases and traits, thus rapidly providing
      key novel insights into disease biology. Since genotype information is fixed,
      with minimum biological variability, it is useful in early life risk prediction.
      However, these variants explain only a small proportion of the observed variance
      of these traits. Therefore, the utility of genetic determinants in assessing risk
      at later stages of life has limited immediate clinical impact. The future
      application of genetic screening will be in identifying risk groups early in life
      to direct targeted preventive measures.

PMID- 21860706
TI  - Apical hypertrophic cardiomyopathy.
AB  - We describe a patient with asymptomatic apical hypertrophic cardiomyopathy (AHCM)
      who later developed cardiac arrhythmias, and briefly discuss the diagnostic
      modalities, differential diagnosis and treatment option for this condition. AHCM
      is a rare form of hypertrophic cardiomyopathy which classically involves the apex
      of the left ventricle. AHCM can be an incidental finding, or patients may present
      with chest pain, palpitations, dyspnea, syncope, atrial fibrillation, myocardial
      infarction, embolic events, ventricular fibrillation and congestive heart
      failure. AHCM is frequently sporadic, but autosomal dominant inheritance has been
      reported in few families. The most frequent and classic electrocardiogram
      findings are giant negative T-waves in the precordial leads which are found in
      the majority of the patients followed by left ventricular (LV) hypertrophy. A
      transthoracic echocardiogram is the initial diagnostic tool in the evaluation of
      AHCM and shows hypertrophy of the LV apex. AHCM may mimic other conditions such
      as LV apical cardiac tumors, LV apical thrombus, isolated ventricular non
      compaction, endomyocardial fibrosis and coronary artery disease. Other
      modalities, including left ventriculography, multislice spiral computed
      tomography, and cardiac magnetic resonance imagings are also valuable tools and
      are frequently used to differentiate AHCH from other conditions. Medications used
      to treat symptomatic patients with AHCM include verapamil, beta-blockers and
      antiarrhythmic agents such as amiodarone and procainamide. An implantable
      cardioverter defibrillator is recommended for high risk patients.

PMID- 21860705
TI  - Phase I of cardiac rehabilitation: A new challenge for evidence based
      physiotherapy.
AB  - Cardiac rehabilitation protocols applied during the in-hospital phase (phase I)
      are subjective and their results are contested when evaluated considering what
      should be the three basic principles of exercise prescription: specificity,
      overload and reversibility. In this review, we focus on the problems associated
      with the models of exercise prescription applied at this early stage in-hospital
      and adopted today, especially the lack of clinical studies demonstrating its
      effectiveness. Moreover, we present the concept of "periodization" as a useful
      tool in the search for better results.

PMID- 21860707
TI  - Coexistence of acute myocardial infarction with normal coronary arteries and
      migraine with aura in a female patient.
AB  - Acute myocardial infarction with normal coronary arteries is a well known
      condition, which is typically diagnosed in young patients. Coronary vasospasm,
      inherited, acquired or malignancy-induced hypercoagulable state, collagen
      vascular disease and coronary arterial embolism have been considered as
      underlying etiologic factors. An association between migraine with aura and
      increased risk of ischemic stroke, angina and myocardial infarction has been
      demonstrated in studies. Patients with migraine and especially with aura should
      be followed closely against cardiovascular events even if they are young and do
      not have traditional risk factors.

PMID- 21860708
TI  - Digital subtraction angiography for the analysis of supra-aortic vessels: What is
      its role nowadays?
AB  - For about 50 years, angiography represented the only imaging method for studying
      carotid arteries in order to detect the presence of pathological stenosis due to
      atherosclerotic plaque. Recently, thanks to the use of non-invasive methods,
      physicians are able to study and quantify the presence of carotid atherosclerosis
      in vivo. These procedures have enabled the introduction of new concepts: (1) the
      degree of carotid stenosis is approximate to the volume and extension of carotid
      plaque; and (2) a set of parameters, easily identifiable by computed tomography
      angiography, magnetic resonance angiogram and ultra-sound echo-color Doppler, are
      closely linked to the development of ischemic symptoms and can significantly
      increase the risk of stroke regardless of the degree of stenosis. In light of
      these findings, vulnerable plaques should be identified early, and the role of
      Digital Subtraction Angiography which is a purely technical luminal technique
      should be determined.

PMID- 21860709
TI  - Small bowel perforation after duodenal stent migration: An interesting case of a
      rare complication.
AB  - Duodenal stents are frequently used for palliating malignant gastric outlet
      obstruction. Successful stent placement relieves obstructive symptoms, is cost
      effective, and has a relatively low complication rate. However, enteral stents
      have the potential of migrating distally and rarely, even lead to bowel
      perforation. We present a rare case of a duodenal stent placed as a palliative
      measure for gastric outlet obstruction due to unresectable pancreatic cancer that
      migrated distally after a gastrojejunostomy resulting in small bowel perforation.

PMID- 21860710
TI  - A body-packer with a cocaine bag stuck in the stomach.
AB  - Management of patients carrying packets of drugs in the digestive tract is a
      frequent medical problem. We report on a patient who was referred by the police
      after ingestion of packets of cocaine. After spontaneous elimination of 81 drug
      packets, the patient had three unremarkable stools. A plain abdominal X-ray
      disclosed no residual packet but computed tomography (CT) scan showed one in the
      stomach. As this was not eliminated during the 10 d following ingestion, it was
      removed through gastrotomy. This case stresses the usefulness of the CT scan to
      ensure that no residual packet is present before hospital discharge.

PMID- 21860711
TI  - Rui Liao's work on patient-specific 3-D model guidance for interventional and
      hybrid-operating-room applications.
AB  - Compared to surgery, interventional and hybrid-operating-room (OR) approaches
      diagnose or treat pathology with the most minimally invasive techniques possible.
      By minimizing the physical trauma to the patient, peripheral or hybrid approaches
      can reduce infection rates and recovery time as well as shorten hospital stays.
      Minimally invasive approaches therefore are the trend and often the preferred
      choice, and may even be the only option for the patients associated with high
      surgery risks. Common interventional imaging modalities include 2-D X-ray
      fluoroscopy and ultrasound. However, fluoroscopic images do not display the
      anatomic structures without a contrast agent, which on the other hand, needs to
      be minimized for patients' safety. Ultrasound images suffer from relatively low
      image quality and tissue contrast problems. To augment the doctor's view of the
      patient's anatomy and help doctors navigate the devices to the targeted area with
      more confidence and a higher accuracy, high-resolution pre-operative volumetric
      data such as computed tomography and/or magnetic resonance can be fused with
      intra-operative 2-D images during interventions. A seamless workflow and accurate
      2-D/3-D registration as well as cardiac and/or respiratory motion compensation
      are the key components for a successful image guidance system using a patient
      specific 3-D model. Dr. Liao's research has been focused on developing methods
      and systems of 3-D model guidance for various interventions and hybrid-OR
      applications. Dr. Liao's work has led to several Siemens products with high
      clinical and/or market impact and a good number of scientific publications in
      leading journals/conferences on medical imaging.

PMID- 21860712
TI  - Imaging and interventions in Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome (BCS) consists of a group of disorders with obstruction of
      hepatic venous outflow leading to increased hepatic sinusoidal pressure and
      portal hypertension. Clinically, two forms of disease (acute and chronic) are
      recognized. Mostly the patients present with ascites, hepatomegaly, and portal
      hypertension. In acute disease the liver is enlarged with thrombosed hepatic
      veins (HV) and ascites, whereas in the chronic form of the disease there may be
      membranous occlusion of HV and/or the inferior vena cava (IVC), or there may be
      short or long segment fibrotic constriction of HV or the suprahepatic IVC. Due to
      advances in radiological interventional techniques and hardware, there have been
      changes in the management protocol of BCS with surgery being offered to patients
      not suitable for radiological interventions or having acute liver failure
      requiring liver transplantation. The present article gives an insight into
      various imaging findings and interventional techniques employed in the management
      of BCS.

PMID- 21860713
TI  - Allergic bronchopulmonary aspergillosis: Lessons for the busy radiologist.
AB  - The probability of a radiologist interpreting a disease correctly is not only
      influenced by their training and experience but also on the knowledge of a
      particular entity. This editorial reviews certain myths and realities associated
      with radiological manifestations of allergic bronchopulmonary aspergillosis
      (ABPA). ABPA is a hypersensitivity disorder against the antigens of Aspergillus
      fumigatus. Although commonly manifesting with central bronchiectasis (CB), the
      disorder can present without any abnormalities on high-resolution computed
      tomography (HRCT) of the chest, so-called serologic ABPA (ABPA-S). HRCT of the
      chest should not be used in screening or in the initial diagnostic work up of
      asthmatics, as asthma without ABPA can manifest with findings of CB. High
      attenuation mucus (HAM) is the pathognomonic sign of ABPA and is very helpful in
      the diagnosis of ABPA complicating asthma and cystic fibrosis. Instead of
      classifying ABPA based on the presence and absence of CB into ABPA-CB and ABPA-S
      respectively, ABPA should be classified as ABPA-S, ABPA-CB and ABPA-CB-HAM. The
      classification scheme based on HAM not only identifies an immunologically severe
      disease but also predicts a patient with increased risk of recurrent relapses.

PMID- 21860714
TI  - Endovascular management in abdominal visceral arterial aneurysms: A pictorial
      essay.
AB  - Visceral artery aneurysms (VAAs) include aneurysms of the splanchnic circulation
      and those of the renal artery. Their diagnosis is clinically important because of
      the associated high mortality and potential complications. Splenic, superior
      mesenteric, gastroduodenal, hepatic and renal arteries are some of the common
      arteries affected by VAAs. Though surgical resection and anastomosis still
      remains the treatment of choice in some of the cases, especially cases involving
      the proximal arteries, increasingly endovascular treatment is being used for more
      distal vessels. We present a pictorial review of various intra-abdominal VAAs and
      their endovascular management.

PMID- 21860715
TI  - Is ARFI elastography reliable for predicting fibrosis severity in chronic HCV
      hepatitis?
AB  - AIM: To determine whether acoustic radiation force impulse (ARFI) elastography is
      a reliable method for predicting fibrosis severity in patients with chronic
      hepatitis C virus (HCV) hepatitis. METHODS: We performed a multicenter study
      including 274 subjects with HCV chronic hepatitis in which we compared ARFI with
      liver biopsy (LB). In each patient we performed LB (evaluated according to the
      Metavir score) and ARFI measurements (using a Siemens Acuson S2000TM ultrasound
      system: 10 valid measurements were performed and median values were calculated
      and expressed in meters/second (m/s). RESULTS: A direct, strong, correlation
      (Spearman r = 0.707) was found between ARFI measurements and fibrosis (P <
      0.0001). For predicting the presence of fibrosis (F >= 1 Metavir), significant
      fibrosis (F >= 2), severe fibrosis (F >= 3) and cirrhosis (F = 4), the cut-off
      values of 1.19, 1.21, 1.58 and 1.82 m/s were determined, respectively, liver
      stiffness measurements had 73%, 84%, 84% and 91% Se respectively; 93%, 91%, 94%,
      90% Sp, respectively; with AUROCs of 0.880, 0.893, 0.908 and 0.937, respectively.
      CONCLUSION: ARFI measurement is a reliable method for predicting the severity of
      fibrosis in HCV patients.

PMID- 21860716
TI  - Antegrade pampiniform plexus venography in recurrent varicocele: Case report and
      anatomy review.
AB  - Varicoceles are often treated with percutaneous embolization, using fibered coils
      and sclerosing agents, with the latter targeted at occlusion of pre-existing
      collateral veins. While various methods of surgical and embolization treatment
      are available, varicoceles may still recur from venous collateralization. We
      present a case, where following demonstration of complete occlusion of the right
      and left gonadal veins, direct puncture of the pampiniform venous plexus under
      ultrasound guidance revealed recurrent varicoceles supplied by anastomoses from
      the ipsilateral saphenous and femoral veins to the pampiniform plexus. In doing
      so, we describe a technique of percutaneous pampiniform venography in a case
      where the pertinent anatomy was not easily demonstrated by other methods.

PMID- 21860717
TI  - Role of echocardiography in atrial fibrillation.
AB  - Atrial fibrillation (AF) is most common arrhythmia and its prevalence appears to
      be increasing as the population ages. Echocardiography can play a key role in
      risk stratification and management of patients with AF. Transthoracic
      echocardiography allows rapid and comprehensive assessment of cardiac anatomical
      structure and function. Pulmonary vein flow monitoring using echocardiography has
      the potential to an increasing role in the evaluation of cardiac function and AF
      ablation procedures. Transesophageal echocardiography also provides accurate
      information about the presence of a thrombus in the atria and thromboembolic
      risk. The novel technique of intracardiac echocardiography has emerged as a
      popular and useful tool in the everyday practice of interventional
      electrophysiology. Other imaging modalities, such as computed tomography and
      magnetic resonance imaging have complementary roles in risk stratification and
      assessment of patients with AF. Echocardiography continues to be the foundation
      of clinical evaluation and management of AF.

PMID- 21860718
TI  - Arterial-cardiac interaction: the concept and implications.
AB  - Vascular stiffening of the large arteries is a common feature of human aging.
      Increased aortic stiffness with age may contribute to pathological changes in the
      left ventricle and this can induce ventricular stiffening. Vascular-ventricular
      stiffening combined with abnormal arterial-cardiac interaction is considered an
      important pathophysiology of heart failure with a preserved ejection fraction.
      Here, I briefly review the concept and implications of arterial-cardiac
      interaction and this will pave the way to understanding and controlling heart
      failure with a preserved ejection fraction, which is more prevalent in the
      elderly.

PMID- 21860719
TI  - The role of mecahnical dyssynchrony on functional mitral regurgitation in
      patients with dilated cardiomyopathy.

PMID- 21860720
TI  - Role of dyssynchrony on functional mitral regurgitation in patients with
      idiopathic dilated cardiomyopathy: a comparison study with geometric parameters
      of mitral apparatus.
AB  - BACKGROUND: Functional mitral regurgitation (FMR) occurs commonly in patients
      with dilated cardiomyopathy (DCM). This study was conducted to explore the role
      of left ventricular (LV) dyssynchrony in developing FMR in patients with DCM in
      comparison with geometric parameters of the mitral apparatus. METHODS: Twenty
      patients without FMR and 33 patients with FMR [effective regurgitant orifice area
      (ERO) = 0.17 +/- 0.10 cm(2)] were enrolled. MR severity was estimated with ERO
      area. Dyssynchrony indices (DI) were measured using the standard deviations of
      time to peak myocardial systolic velocity between eight segments. Using real time
      3D echocardiography, mitral valve tenting area (MVTa), anterior (APMD) and
      posterior papillary muscle distances (PPMD), LV sphericity, and tethering angle
      of anterior (Aalpha) and posterior leaflets (Palpha) were estimated. All
      geometrical measurements were corrected (c) by the height of each patient.
      RESULTS: The patient with FMR had significantly higher cDI, cMVTa, cAPMD and
      cPPMD, LV sphericity, Aalpha, and Palpha than the patients without FMR (all p <
      0.05). With multiple logistic regression analysis, cMVTa (p = 0.017) found to be
      strongest predictor of FMR development. In patients with FMR, cMVTa (r = 0.868),
      cAPMD (r = 0.801), cPPMD (r = 0.742), Aalpha (r = 0.454), LV sphericity (r =
      0.452), and DI (r = 0.410) showed significant correlation with ERO. On
      multivariate regression analysis, cMVTa and cAPMD (p < 0.001, p = 0.022,
      respectively) remained the strongest determinants of the degree of ERO and cAPMD
      (p < 0.001) remained the strongest determinant of the degree of cMVTa.
      CONCLUSION: Displacement of anterior papillary muscle and consequent mitral valve
      tenting seem to play a major role in developing FMR in DCM, while LV dyssynchrony
      seems to have no significant role.

PMID- 21860721
TI  - Prevalence and patterns of left ventricular dysfunction in patients with
      pheochromocytoma.
AB  - BACKGROUND: Excessive catecholamine release in pheochromocytoma is known to cause
      transient reversible left ventricular (LV) dysfunction, such as in the case of
      pheochromocytoma-associated catecholamine cardiomyopathy. We investigated
      patterns of clinical presentation and incidence of LV dysfunction in patients
      with pheochromocytoma. METHODS: From January 2004 to April 2011, consecutive
      patients with pheochromocytoma were retrospectively studied with clinical
      symptoms, serum catecholamine profiles, and radiologic findings. Patterns of
      electrocardiography and echocardiography were also analyzed. RESULTS: During the
      study period, a total of 36 patients (21 males, 49.8 +/- 15.8 years, range 14-81
      years) with pheochromocytoma were included. In the electrocardiographic
      examinations, normal findings were the most common findings (19, 52.8%). LV
      hypertrophy in 12 cases (33.3%), sinus tachycardia in 3 (8.3%), ischemic pattern
      in 1 (2.8%) and supraventricular tachycardia in 1 (2.8%). Echocardiographic exam
      was done in 29 patients (80.6%). Eighteen patients (62.1%) showed normal finding,
      8 (27.6%) revealed concentric LV hypertrophy with normal LV systolic function,
      and 3 (10.3%) demonstrate LV systolic dysfunction (LV ejection fraction < 50%).
      Three showed transient LV dysfunction (2 with inverted Takotsubo-type
      cardiomyopathy and 1 with a diffuse hypokinesia pattern). Common presenting
      symptoms in the 3 cases were new onset chest discomfort and dyspnea which were
      not common in the other patients. Their echocardiographic abnormalities were
      normalized with conventional treatment within 3 days. CONCLUSION: Out of total 36
      patients with pheochromocytoma, 3 showed transient LV systolic dysfunction
      (catecholamine cardiomyopathy). Pheochromocytoma should be included as one of
      possible causes of transient LV systolic dysfunction.

PMID- 21860722
TI  - A case report of carbon monoxide poisoning induced cardiomyopathy complicated
      with left ventricular thrombus.
AB  - The heart and the brain, most oxygen-dependent organs, may be severely affected
      after carbon monoxide (CO) exposure. CO induced cardiotoxicity may occur as a
      consequence of moderate to severe CO poisoning, including angina attack,
      myocardial infarct, arrhythmias, and heart failure. We present a rare case of CO
      poisoning induced cardiomyopathy with left ventricular (LV) thrombus. It is
      thought that LV thrombus may have been caused severely decreased LV function with
      dyskinesis. After short-term anticoagulant therapy, echocardiography findings
      revealed complete recovery of LV dyskinesis and resolution of LV thrombus.

PMID- 21860723
TI  - Stress cardiomyopathy complicated by left ventricular thrombi and cerebral
      infarctions in a patient with essential thrombocythemia.
AB  - The prognosis of stress induced cardiomyopathy (SCMP) is generally known to be
      excellent, however, several fatal complications such as cardiac rupture and left
      ventricular (LV) thrombosis with subsequent embolic complications have been
      described. We report a rare case of SCMP complicated by LV thrombosis and
      multiple cerebral infarctions in a patient with essential thrombocythemia. After
      intravenous anticoagulation with heparin and general managements for heart
      failure and cerebral infarctions, her neurologic symptoms and the wall motion
      abnormalities of the LV apex were improved, and the thrombus was disappeared on
      follow-up echocardiography.

PMID- 21860724
TI  - Unusual Presentation Chronic Pulmonary Embolism due to Calcified Right
      Ventricular Mass.
AB  - Cardiac calcified amorphous tumors (CATs) can arise in all four chambers of the
      heart. Cardiac CATs can cause diverse symptoms according to their locations, and
      mass or embolic effects. Pulmonary emboli arising from cardiac CATs have been
      reported, but the true incidence is unknown due to their rarity. Herein we report
      a rare case with diffuse CATs in the right ventricle which caused a calcific
      pulmonary embolism and right-sided heart failure. Echocardiography, chest non
      contrast computed tomography, and cardiac magnetic resonance imaging helped us
      diagnose the CATs. We recommend the usefulness of a multimodality imaging
      approach to characterize intracardiac masses and their complications accurately.

PMID- 21860725
TI  - Reversible Symptomatic Myocarditis Induced by All-Trans Retinoic Acid
      Administration during Induction Treatment of Acute Promyelocytic Leukemia: Rare
      Cardiac Manifestation as a Retinoic Acid Syndrome.
AB  - Treatment by All-trans retinoic acid (ATRA) followed by anthracycline-AraC
      chemotherapy has improved the outcome of acute promyelocytic leukemia. ATRA is
      usually well tolerated, but a few major side effects can be observed. Retinoic
      acid syndrome (RAS) often occurs during the induction chemotherapy of acute
      promyelocytic leukemia. A pericardial effusion is a common cardiac manifestation
      but myocarditis has been rarely documented. Here we reports a very rare case of
      fully recovered myocarditis as a result of RAS related to ATRA administration
      during induction treatment of acute promyelocytic leukemia which documented by
      echocardiographic evidence.

PMID- 21860726
TI  - Carcinoid Heart Disease: A Rare Cause of Right Ventricular Dysfunction Evaluation
      by Transthoracic 2D, Doppler and 3-D Echocardiography.
AB  - Carcinoid heart disease is a rare cause of heart failure with or without right
      valvular heart impairments. In this study, we showed a case of carcinoid tumour
      with hepatic metastases inducing carcinoid heart disease. Neuroendocrine heart
      involvement happens for severe tricuspid valve insufficiency and plaques on right
      ventricular (RV) walls produced by a release of serotonin (5-HT). A patient
      affected by primitive ileal tumour with 5-HT-secernent hepatic metastases
      inducing tricuspid insufficiency is showed. Transthoracic 2-D echocardiography
      showed tricuspid valve regurgitation and both right atrium, RV-walls plaques and
      RV dilation. Continue-wave Doppler showed a characteristic "dagger shaped"
      spectrum of tricuspid systolic flow. RV function was evaluated with 3-D
      transthoracic echocardiography. In particular, RV volumes, RV ejection fraction
      and stroke volume were defined by this technique. 2, 3-D echocardiography and
      Doppler method are useful techniques to show heart valves' derangements and RV
      function to non-invasively detect RV impairments in carcinoid heart disease.

PMID- 21860727
TI  - Incidental diagnosis of the unicuspid aortic valve with ascending aortic aneurysm
      in an asymptomatic adult.
AB  - The unicuspid aortic valve is an extremely rare congenital anomaly. It usually
      presents with aortic stenosis and/or aortic regurgitation. Other cardiovascular
      complications, such as aortic dilatation and left ventricular hypertrophy can
      accompany it. Herein, we present a case report of a 50-year-old asymptomatic male
      patient with unicuspid aortic valve, complicated by ascending aortic aneurysm.

PMID- 21860728
TI  - Retained subintimal pellet in a carotid artery.
AB  - A shotgun pellet is depicted in the present image in a carotid artery under the
      intima, which remained intact without local complications for up to six months.
      There is lack of data regarding the natural history of such a carotid pellet, but
      the experience from the myocardium is that, in the absence of infection,
      completely embedded missiles are usually asymptomatic, tolerated well and may be
      left in place.

PMID- 21860729
TI  - Taking medical humanities forward.

PMID- 21860730
TI  - Robotic single-site surgery: from research to clinical practice?

PMID- 21860731
TI  - Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine:
      immunogenicity and safety in 15-25 years old healthy Korean women.
AB  - OBJECTIVE: The study assessed the immunogenicity and safety of human
      papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy
      Korean women aged 15-25 years. METHODS: Phase IIIB, double-blind, randomised
      (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008.
      The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who
      received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium
      hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed
      until one month post-dose 3. Serum samples were collected pre-vaccination and one
      month post-dose 3. Safety and reactogenicity data were collected throughout.
      RESULTS: In this trial, 208 women completed the study (141 in HPV group; 67 in
      placebo group). At month 7, all initially seronegative women had seroconverted
      for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean
      titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95%
      CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed
      similar increase in geometric mean titre levels. Compliance to the three dose
      vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local
      (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported
      in both groups. Three serious adverse events were reported (two in HPV group; one
      in placebo group), all unrelated to vaccination by the investigator; all
      recovered. CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was highly
      immunogenic with a clinically acceptable safety profile in Korean women. This
      study was in line with previous global studies in Europe, North America, and
      Brazil. (ClinicalTrials.gov number, NCT 00485732.).

PMID- 21860732
TI  - Cervical cancer in the screening era: who fell victim in spite of successful
      screening programs?
AB  - OBJECTIVE: To compare profiles of a prescreening and screening cohort of women
      with cervical cancer regarding histopathology and clinical variables in order to
      identify those remaining at risk despite successful screening programs. By
      analyzing these profiles we hope to improve future screening methods. METHODS:
      The prescreening and screening cohorts consisted of 5,046 and 1,174 women,
      respectively, treated for cervical cancer at the Department of Gynecological
      Oncology at Radiumhemmet, Karolinska University Hospital, during the periods 1944
      1957 and 1990-2004. RESULTS: Mean age increased from 48.9 years to 55.3 years in
      the cohorts treated 1944-1957 and 1990-2004, respectively. The percentage of
      patients older than 69 years was 5.4% and 27.3% in the prescreening and screening
      period, respectively. A shift towards earlier stages at diagnosis, a reduction of
      squamous cervical cancer and an increase of adenocarcinoma were observed in the
      screening cohort. The percentage of adenocarcinoma was about 6 times higher among
      younger patients. Cases of stump cancer and cervical cancer associated with
      pregnancy have declined. Eighty-seven women in the screening cohort had a history
      of treatment for in situ carcinoma by conization; 28% of these cases developed
      cervical cancer within one year after conization. CONCLUSION: The profile changed
      in the screening era indicating a need to refine screening for improved detection
      of in older women. This study, one of the largest clinical series of cervical
      cancer, provides an important baseline with which later studies can be compared
      to evaluate the effects of human papillomavirus vaccine and other important
      changes in this field.

PMID- 21860733
TI  - Which is worse: uterine papillary serous carcinomas or carcinosarcomas?
AB  - OBJECTIVE: It is clear that uterine carcinosarcomas and uterine papillary serous
      carcinomas (UPSC) have an adverse impact on outcome, but whether carcinosarcomas
      are worse than UPSC is unclear. The purpose of this study is to compare the
      pathology, survival, and disease recurrence of patients with carcinosarcomas to
      patients with UPSC. METHODS: The medical records of patients diagnosed with
      carcinosarcomas and UPSC between 1996 and 2009 at Samsung Medical Center were
      retrospectively analyzed. Information from pathology reports, site of relapse,
      time to recurrence, and death was obtained. The survival analysis was performed
      using the Kaplan-Meier method. RESULTS: Thirty seven patients with
      carcinosarcomas and 38 patients with UPSC were identified during the study
      period. There was no significant difference in clinical characteristics including
      age, body mass index, proportion with advanced stage disease, rate of optimal
      debulking, and adjuvant treatment used. In addition, the pathology showed no
      significant difference in tumor size, myometrial involvement, lymphovascular
      invasion, peritoneal cytology, cervical invasion, and lymph node involvement.
      Patients with carcinosarcomas had similar patterns of relapse as the patients
      with UPSC. There was no difference in the progression-free and overall survival
      between the carcinosarcomas and UPSC patients (p=0.804 and p=0.651,
      respectively). CONCLUSION: Patients with carcinosarcomas had similar
      clinicopathological features compared to the patients with UPSC.

PMID- 21860734
TI  - Expression of matrix metalloproteinase-2 and survivin in endometrioid and
      nonendometrioid endometrial cancers and clinicopathologic significance.
AB  - OBJECTIVE: To determine matrix metalloproteinase-2 and survivin expressions in
      endometrial cancers, their relation to clinical and histologic parameters and to
      investigate any difference in the expression of these markers between
      endometrioid and nonendometrioid cancers. METHODS: Ninety-five patients with
      endometrial cancer, were included. Matrix metalloproteinase-2 and survivin
      expressions were analyzed immunohistochemically from paraffin-embedded tissues by
      using specific monoclonal antibodies. RESULTS: Survivin nuclear expression was
      higher in endometrioid cancer as compared to nonendometrioid cancer (p=0.040),
      but there was no difference for cytoplasmic survivin and matrix metalloproteinase
      2 expressions between type I and type II carcinomas. Survivin cytoplasmic
      staining was significantly lower in patients with deep myometrial invasion
      (p=0.038). Nuclear expression of survivin is decreased in histologic grade 3
      tumors compared to grade 1 and 2 tumors (p=0.013), but there is no difference
      between grade 1 and 2. We did not find any statistically significant difference
      between survivin or matrix metalloproteinase-2 expressions and survival.
      CONCLUSION: Survivin and matrix metalloproteinase-2 are present in endometrioid
      and nonendometrioid cancers. Grade 1 and 2 tumors and carcinomas having
      myometrial invasion less than 50% have higher survivin expression. These results
      supports that, survivin may play an important role in early stage tumors and
      early phases of tumor development. We did not find any association between matrix
      metalloproteinase-2 expression and classical prognostic factors in endometrial
      cancer and both proteins were not associated with survival.

PMID- 21860735
TI  - Major surgeries performed for gestational trophoblastic neoplasms in a teaching
      hospital in Tehran, Iran.
AB  - OBJECTIVE: This study aim was to evaluate indications and outcomes of surgical
      interventions performed in patients with gestational trophoblastic neoplasm.
      METHODS: During January 1995 to December 2005, 110 patients with a diagnosis of
      persistent gestational trophoblastic neoplasm were treated in our Gynecologic
      Oncologic Department. Risk score calculation was carried out based on the revised
      FIGO 2000 scoring system for gestational trophoblastic neoplasm. Data from the
      patients' records and pathologic reports were analyzed by the chi-square and
      Fisher's exact tests and logistic regression. The Kaplan-Meier method including
      the log rank test was used to compare survival and recurrence. RESULTS: Eight
      patients did not complete their treatment and were excluded from the study. We
      evaluated treatment responses and outcomes in 102 patients. Seventy-nine patients
      (77.5%) responded fully to chemotherapy while 23 patients (22.5%) required
      surgery. Among 23 patients who underwent surgery, 10 cases (43.5%) had bleeding,
      and 13 cases (56.5%) had drug resistance. Several factors were found to be
      significantly different between the groups who responded to chemotherapy and
      those who needed surgery, including age (p=0.001), antecedent non-molar pregnancy
      (0.028), tumor stage (p=0.009), and pre-treatment risk scores (p=0.008). But, the
      total courses of chemotherapy (p=0.521), need to salvage chemotherapy (p=0.074),
      survival rates (p=0.714), and disease free survival rates (p=0.206) were not
      significantly different. CONCLUSION: The data suggest that age, antecedent non
      molar pregnancy, tumor stage and the prognostic score are clinical predictors of
      need for surgery. But, it dose not seem that surgery have any effect on the total
      course of chemotherapy, need for salvage chemotherapy, and patient prognosis.

PMID- 21860736
TI  - Quality of life in gynecologic cancer survivors compared to healthy check-up
      women.
AB  - OBJECTIVE: The primary objective of this study was to compare quality of life of
      disease-free patients after therapy for gynecologic malignancies at follow-up in
      comparison with healthy check-up patients. Our second objective was to assess
      correlation between demographic data, disease and treatment factors and quality
      of life scores. METHODS: Patients completed the Functional Assessment of Cancer
      Therapy-General (FACT-G) quality of life questionnaire at least 6 months after
      treatment for a gynecologic malignancy. Responses were compared to unmatched
      healthy women who were seen for standard gynecologic screening examinations.
      Statistical calculation was done using chi-squared tests, Wilcoxon rank-sum, and
      Kruskal-Wallis one-way analysis and Spearman rank correlations. Factors
      associated with FACT-G scores were evaluated using univariate and multivariate
      analyses. RESULTS: Eight hundred and seventy patients were recruited. The median
      time since therapy was 61 months (range, 6 to 173 months). The overall FACT-G
      scores were higher in the patient group than in the healthy group (p<0.05). The
      scores of each subscale measuring physical, functional, social/family and
      emotional well-being were also higher in the patient group (p<0.05). Multivariate
      analysis revealed correlation between Eastern Cooperative Oncology Group
      performance status, educational level, care giver, presence of economic problems
      and FACT-G scores. CONCLUSION: The quality of life scores were higher in
      gynecologic cancer patients after treatment. And the factors that associated with
      the higher score in the patient group are having husband as a caregiver, no
      financial problem, Eastern Cooperative Oncology Group score 0 or 1 and having
      high school or higher education.

PMID- 21860737
TI  - Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of
      postmenopausal breast cancer.
AB  - OBJECTIVE: Estrogen plays a key role in breast cancer development and
      functionally relevant genetic variants within the estrogen metabolic pathway are
      prime candidates for a possible association with breast cancer risk. We
      investigated the independent and the combined effects of commonly occurring
      polymorphisms in four genes encoding key proteins of estrogen metabolic pathway
      on their potential contribution to breast cancer risk. METHODS: We studied 530
      breast cancer cases and 270 controls of the same age and ethnicity participating
      in a case-control study of postmenopausal women. Genotyping was conducted for
      CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), and MnSOD (rs4880)
      polymorphisms by polymerase chain reaction based restriction fragment length
      polymorphism and TaqMan allelic discrimination method. Adjusted ORs and 95% CIs
      were calculated using logistic regression. RESULTS: None of the 4 genetic
      variants examined contributed to breast cancer risk individually. When the
      combined effects of the risk genotypes were investigated, significant
      associations were observed among women with two high-risk genotypes in CYP1B1 and
      COMT (OR, 2.0; 95% CI, 1.1 to 3.5) and two high-risk genotypes in COMT and MnSOD
      (OR, 2.0; 95% CI, 1.0 to 3.8), compared to those with low-risk genotypes.
      CONCLUSION: Our results suggest that individual susceptibility to breast cancer
      incidence may be increased by combined effects of the high-risk genotypes in
      CYP1B1, COMT, and MnSOD estrogen metabolic genes.

PMID- 21860739
TI  - Single-port access laparoscopic staging operation for a borderline ovarian tumor.
AB  - Minimally invasive surgery is widely used in benign gynecologic diseases and may
      be used in malignancies. We performed a single-port access laparoscopy staging -
      bilateral salpingo-oophorectomy, laparoscopy-assisted vaginal hysterectomy,
      bilateral pelvic lymphadenectomy, infracolic omentectomy, and washing cytology -
      in a borderline ovarian tumor. The number of harvested pelvic lymph nodes were
      twenty-three and there were no intraoperative or postoperative complications.
      Single-port access laparoscopic staging may be performed in selected patients.
      The efficacy, safety, and potential benefits of this technique should be
      evaluated in further trials.

PMID- 21860738
TI  - Robotic single-port transumbilical total hysterectomy: a pilot study.
AB  - OBJECTIVE: To evaluate the feasibility of robotic single-port transumbilical
      total hysterectomy using a home-made surgical glove port system. METHODS: We
      retrospectively reviewed the medical records of patients who underwent robotic
      single-port transumbilical total hysterectomy between January 2010 and July 2010.
      All surgical procedures were performed through a single 3-4-cm umbilical
      incision, with a multi-channel system consisting of a wound retractor, a surgical
      glove, and two 10/12-mm and two 8 mm trocars. RESULTS: Seven patients were
      treated with robotic single-port transumbilical total hysterectomy. Procedures
      included total hysterectomy due to benign gynecological disease (n=5), extra
      fascial hysterectomy due to carcinoma in situ of the cervix (n=1), and radical
      hysterectomy due to cervical cancer IB1 (n=1). The median total operative time
      was 109 minutes (range, 105 to 311 minutes), the median blood loss was 100 mL
      (range, 10 to 750 mL), and the median weight of the resected uteri was 200 g
      (range, 40 to 310 g). One benign case was converted to 3-port robotic surgery due
      to severe pelvic adhesions, and no post-operative complications occurred.
      CONCLUSION: Robotic single-port transumbilical total hysterectomy is technically
      feasible in selected patients with gynecological disease. Robotics may enhance
      surgical skills during single-port transumbilical hysterectomy, especially in
      patients with gynecologic cancers.

PMID- 21860740
TI  - Sonographic diagnosis and Endo-SPONGE assisted vacuum therapy of anastomotic
      leakage following posterior pelvic exenteration for ovarian cancer without using
      a protective stoma.
AB  - Anastomotic leakage is a very significant complication after posterior pelvic
      exenteration and a major cause of postoperative morbidity and mortality. We
      present a patient who underwent an optimal debulking surgery for an advanced
      stage ovarian cancer (FIGO IIIC). On postoperative day 12, transvaginal
      ultrasound revealed an anastomotic dehiscence following an unsuspicious computer
      tomography scan the day before. The patient was successfully managed by transanal
      vacuum therapy without re-laparotomy within a period of 4 weeks after diagnosis.
      We conclude that high-resolution transvaginal ultrasound is a crucial method in
      the management of complications after surgery and even allow diagnosing leakages
      of colorectal anastomosis. In selected cases characterized by a small leak size
      and a local peritonitis confined to the pelvis a transanal vacuum therapy may
      avoid both surgical re-intervention and creating a secondary diverting stoma.

PMID- 21860741
TI  - Pure choriocarcinoma of the ovary: a case report.
AB  - Pure ovarian choriocarcinomas are extremely rare and aggressive tumors which are
      gestational or non-gestational in origin. Due to the rarity of the tumor, there
      is a lack of information on the clinicopathologic features, diagnosis, and
      treatment. We report a case of a pure ovarian choriocarcinoma, likely of non
      gestational origin, treated by cytoreductive surgery in combination with post
      operative chemotherapy. The patient was free of disease after a 12-month follow
      up.

PMID- 21860742
TI  - Discharge criteria should be validated in patients who undergo ambulatory
      gynecologic surgery.

PMID- 21860743
TI  - B-type natriuretic peptide in anesthesia practice to predict adverse
      cardiovascular outcomes.

PMID- 21860745
TI  - Axillary approach versus the infraclavicular approach in ultrasound-guided
      brachial plexus block: comparison of anesthetic time.
AB  - BACKGROUND: With ultrasound guidance, the success rate of brachial plexus block
      (BPB) is 95-100% and the anesthetic time has become a more important factor than
      before. Many investigators have compared ultrasound guidance with the nerve
      stimulation technique, but there are few studies comparing different approaches
      via the same ultrasound guidance. We compared the axillary BPB with the
      infraclavicular BPB under ultrasound guidance. METHODS: Twenty-two ASA physical
      status I-II patients presenting with elective forearm surgery were prospectively
      randomized to receive an axillary BPB (group AX) or an infraclavicular BPB (group
      IC) with ultrasound guidance. Both groups received a total of 20 ml of 1.5%
      lidocaine with 5 ug/ml epinephrine and 0.1 mEq/ml sodium bicarbonate. Patients
      were then evaluated for block onset and block performance time was also recorded.
      RESULTS: Group IC demonstrated a reduction in performance time vs. group AX (622
      +/- 139 sec vs. 789 +/- 131 sec, P < 0.05). But, the onset time was longer in
      group IC than in group AX (7.7 +/- 8.8 min vs. 1.4 +/- 2.3 min, P < 0.05). All
      blocks were successful in both groups. CONCLUSIONS: Under ultrasound guidance,
      infraclavicular BPB was faster to perform than the axillary approach. But the
      block onset was slower with the infraclavicular approach.

PMID- 21860744
TI  - Endothelial arginase II and atherosclerosis.
AB  - Atherosclerotic vascular disease is the leading cause of morbidity and mortality
      in developed countries. While it is a complex condition resulting from numerous
      genetic and environmental factors, it is well recognized that oxidized low
      density lipoprotein produces pro-atherogenic effects in endothelial cells (ECs)
      by inducing the expression of adhesion molecules, stimulating EC apoptosis,
      inducing superoxide anion formation and impairing protective endothelial nitric
      oxide (NO) formation. Emerging evidence suggests that the enzyme arginase
      reciprocally regulates NO synthase and NO production by competing for the common
      substrate L-arginine. As oxidized LDL (OxLDL) results in arginase
      activation/upregulation, it appears to be an important contributor to endothelial
      dysfunction by a mechanism that involves substrate limitation for endothelial NO
      synthase (eNOS) and NO synthesis. Additionally, arginase enhances production of
      reactive oxygen species by eNOS. Arginase inhibition in hypercholesterolemic
      (ApoE(-/-)) mice or arginase II deletion (ArgII(-/-)) mice restores endothelial
      vasorelaxant function, reduces vascular stiffness and markedly reduces
      atherosclerotic plaque burden. Furthermore, arginase activation contributes to
      vascular changes including polyamine-dependent vascular smooth muscle cell
      proliferation and collagen synthesis. Collectively, arginase may play a key role
      in the prevention and treatment of atherosclerotic vascular disease.

PMID- 21860746
TI  - A comparison of the Glidescope(r) to the McGrath(r) videolaryngoscope in
      patients.
AB  - BACKGROUND: The Glidescope(r) videolaryngoscope is a new device for tracheal
      intubation that provides an improved view of the larynx. This study was performed
      to compare the Glidescope with the McGrath videolaryngoscope in terms of time to
      intubation (TTI) and number of attempts. METHODS: Patients were randomly
      allocated to one of two groups, Glidescope or McGrath group, by using computer
      generated numbers. Tracheal intubation was attempted by an anesthesiologist with
      extensive experience using these two devices. The operator recorded ease of
      visualization of glottic structures based on the classification described by
      Cormack and Lehane. Number of failures, number of attempts and their duration,
      total intubation time, and events during the whole procedure were recorded. The
      duration of one attempt was defined as the time elapsed between picking up the
      endotracheal tube and verification of tracheal intubation with visualization of
      three expiratory carbon dioxide waveforms. TTI was defined as the sum of the
      duration of all intubation attempts (as many as three), excluding preoxygenation
      procedures. RESULTS: TTI was significantly shorter for the Glidescope(r) compared
      to the McGrath(r) laryngoscope (40.5 vs. 53.3 s, respectively, P < 0.05).
      However, glottic views obtained at intubation were similar between the two
      groups. Number of intubation attempts was not significantly different between the
      two groups (1.03 +/- 0.19 vs 1.10 +/- 0.32, respectively) (mean +/- SD).
      CONCLUSIONS: Study results demonstrated that the Glidescope reduced total
      intubation time in comparison with the McGrath, in terms of TTI in patients with
      normal airways.

PMID- 21860747
TI  - The effect of tracheal tube size on air leak around the cuffs.
AB  - BACKGROUND: This randomized single-blinded, cross-over study was done to evaluate
      the influence of the size of tracheal tubes on air leaks around the cuffs.
      METHODS: In a benchtop model, the number of longitudinal folds on the cuffs was
      evaluated for different sizes of tracheal tubes. In an anesthetized patient
      study, thirty patients scheduled for elective surgery under general anesthesia
      were included. After induction of anesthesia, the trachea was intubated with two
      sizes of tracheal tubes in a random sequence: in men, internal diameter of 7.5 mm
      and 8.0 mm; in women, internal diameter of 7.0 mm and 7.5 mm. After tracheal
      intubation with each tube, air leak pressures were evaluated at intracuff
      pressures of 20, 25 and 30 cmH(2)O by auscultation. To calculate the tracheal
      tube resistance (R), an inspiratory pause of 20% was applied and the resulting
      peak airway pressure (P(peak)), plateau pressure (P(pl)) and mean expiratory
      tidal volume (Flow) were inserted in the formula R = (P(peak) - P(pl))/Flow.
      RESULTS: More longitudinal folds of the tracheal tube cuffs occurred in larger
      sized tubes compared to the smaller ones in a benchtop model. Air leakage was
      significantly less for the smaller tracheal tubes than for the larger ones for
      each gender at intracuff pressures of 20, 25 and 30 cmH(2)O. Tracheal tube
      resistances were not significantly altered by the size of tracheal tube.
      CONCLUSIONS: The use of a smaller tracheal tube within an acceptable size can
      reduce air leakage around the cuff without significantly changing the tracheal
      tube resistance.

PMID- 21860748
TI  - Prevention of microemulsion propofol injection pain: a comparison of a
      combination of lidocaine and ramosetron with lidocaine or ramosetron alone.
AB  - BACKGROUND: A microemulsion propofol causes a high incidence of pain during
      intravenous injection. In this study, we investigated the effect of ramosetron on
      pain induced by microemulsion propofol injection. METHODS: After prospective
      power analysis and institutional review board approval, a total of 200 ASA I and
      II patients undergoing general anesthesia were divided into 4 groups. They
      received one of the following intravenously after tourniquet application on the
      forearm 1 min before induction of anesthesia using microemulsion propofol; normal
      saline (Group N, n = 50), lidocaine 20 mg (Group L, n = 50), ramosetron 0.3 mg
      (Group R, n = 50) and lidocaine 20 mg plus ramosetron 0.3 mg (Group LR, n = 50)
      diluted into a 5 ml solution. The occlusion was released after 30 seconds and
      microemulsion propofol was injected over 10-15 seconds. The patients were
      observed and asked immediately if they had pain in the arm, and their responses
      were assessed. RESULTS: The incidence of pain in groups N, L, R and LR was 96%,
      76%, 60% and 38%, respectively (P < 0.008). Two patients in Group LR (4.0%) and
      nine in Group R (18.0%) had moderate to severe pain, which was significantly
      lower than pain in Groups N (84.0%), L (40.0%) and R (P < 0.008). CONCLUSIONS:
      Pretreatment with ramosetron 0.3 mg with or without lidocaine 20 mg with a
      tourniquet on the forearm 30 seconds before the injection of microemulsion
      propofol is more effective than lidocaine 20 mg or normal saline in preventing
      pain from a microemulsion propofol injection.

PMID- 21860749
TI  - Relationship between N-terminal pro-B-type natriuretic peptide and renal
      function: the effects on predicting early outcome after off-pump coronary artery
      bypass surgery.
AB  - BACKGROUND: Plasma levels of N-terminal pro-B-type natriuretic peptide (NT
      proBNP) provide useful prognostic predictors in patients after cardiac surgery.
      However, predictive accuracy of NT-proBNP levels has varied significantly
      according to renal dysfunction. The purpose of this study was to assess whether
      preoperative NT-proBNP levels could be used as predictors of early postoperative
      outcomes on the basis of renal function in patients undergoing off-pump coronary
      artery bypass surgery (OPCAB). METHODS: In 219 patients undergoing elective
      OPCAB, NT-proBNP and an estimated glomerular filtration rate (eGFR) were assessed
      preoperatively. All patients were divided into 3 groups according to tertiles of
      eGFR: the first (eGFR >= 90 ml/min/1.73 m(2)), the second (90 ml/min/1.73 m(2) >
      eGFR >= 72 ml/min/1.73 m(2)) and the third tertile group (eGFR < 72 ml/min/1.73
      m(2)). End point was the composite of early postoperative complications defined
      as myocardial infarction, new onset atrial fibrillation, ventricular dysfunction,
      prolonged mechanical ventilator care (> 48 hr), prolonged ICU stay (>= 3 days),
      and in hospital mortality. RESULTS: There was no difference in early
      postoperative complications among groups. A preoperative NT-proBNP level of 228
      pg/ml and 302 pg/ml (sensitivity 70%, specificity 67%, P < 0.001 and sensitivity
      73%, specificity 63%, P = 0.001, respectively) were optimal cut-off values
      predicting complicated early postoperative course in second and third tertile
      group, respectively. CONCLUSIONS: Preoperative NT-proBNP levels seem to be
      predictive of early postoperative complications in patients with eGFR < 90
      ml/min/1.73 m(2) undergoing OPCAB.

PMID- 21860750
TI  - The efficiency of IV PCA with remifentanil and ketorolac after laparoscopic
      assisted vaginal hysterectomy.
AB  - BACKGROUND: This randomized, double-blinded clinical study was designed to
      evaluate the efficiency and safety of remifentanil with ketorolac for IV PCA
      after laparoscopic-assisted vaginal hysterectomy. METHODS: Eighty patients were
      randomly allocated into four groups. Group R received IV PCA using only
      remifentanil at a basal rate of 0.025 ug/kg/min and a bolus of 0.375 ug/kg. Group
      RK1 received IV PCA using remifentanil at a basal rate of 0.015 ug/kg/min and a
      bolus of 0.225 ug/kg. Group RK2 received IV PCA using remifentanil at a basal
      rate of 0.0075 ug/kg/min and a bolus of 0.1125 ug/kg. Group F received IV PCA
      using fentanyl at a basal rate of 0.3 ug/kg/h and a bolus of 0.075 ug/kg. In
      addition, ketorolac at a basal rate of 0.04 mg/kg/h and a bolus of 0.01 mg/kg was
      added to Group RK1, RK2, and F. All PCA conditions had a lock out period of 15
      minutes. Pulse rate, systolic and diastolic BP, sedation score, visual analogue
      scale (VAS), and PONV score were recorded at 1, 3, 6, 12, and 24 hours after the
      operation. Total opioid use and the patients' number for rescue analgesic drug
      were also collected. RESULTS: The groups did not differ in PONV score and
      hemodynamic changes. The VAS in Group RK2 was high compared with the other
      groups. In addition, the sedation score was high in Group R. CONCLUSIONS: The
      additional ketorolac administration in remifentanil IV PCA had remifentanil
      sparing effects and reduced sedation among the side effects. Further studies will
      be needed to evaluate the precise and adequate dosage of ketorolac.

PMID- 21860751
TI  - Ultrasound-guided greater occipital nerve block for patients with occipital
      headache and short term follow up.
AB  - BACKGROUND: The greater occipital nerve (GON) block has been frequently used for
      different types of headache, but performed with rough estimates of anatomic
      landmarks. Our study presents the values of the anatomic parameters and estimates
      the effectiveness of the ultrasound-guided GON blockade. METHODS: The GON was
      detected using ultrasound technique and distance from external occipital
      protuberance (EOP) to GON, from GON to occipital artery and depth from skin to
      GON was measured in volunteers. Patients with occipital headache were divided
      into two groups (ultrasound-guided block: group S, conventional blind block:
      group B) and GON block was performed. The same parameters were measured on group
      S and VAS scores were assessed at pretreatment, 1 week and 4 weeks after
      treatment on both groups. RESULTS: The GON had distance of 23.1 +/- 3.4 mm
      (right) and 20.5 +/- 2.8 mm (left) from EOP to GON. Its depth below the skin was
      6.8 +/- 1.5 mm (right) and 7.0 +/- 1.3 mm (left). The distance from GON to
      occipital artery was 1.5 +/- 0.6 mm (right) and 1.2 +/- 0.6 mm (left) in
      volunteers. Initial VAS score of group S and group B patients were 6.4 +/- 0.2
      and 6.5 +/- 0.2. VAS score of 4 weeks after injection were 2.3 +/- 0.2 on group S
      and 3.8 +/- 0.3 on group B (P = 0.0003). CONCLUSIONS: The parameters measured in
      this study should be useful for GON block and ultrasound-guided blockade is
      likely to be a more effective technique than blind blockade in occipital headache
      treatment.

PMID- 21860752
TI  - Indigo carmine enhances phenylephrine-induced contractions in an isolated rat
      aorta.
AB  - BACKGROUND: The intravenous administration of indigo carmine has been reported to
      produce transiently increased blood pressure in patients. The goal of this in
      vitro study was to examine the effect of indigo carmine on phenylephrine-induced
      contractions in an isolated rat aorta and to determine the associated cellular
      mechanism with particular focus on the endothelium-derived vasodilators. METHODS:
      The concentration-response curves for phenylephrine were generated in the
      presence or absence of indigo carmine. Phenylephrine concentration-response
      curves were generated for the endothelium-intact rings pretreated independently
      with a nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L
      NAME), a cyclooxygenase inhibitor, indomethacin, and a low-molecular-weight
      superoxide anion scavenger, tiron, in the presence or absence of indigo carmine.
      The fluorescence of oxidized dichlorofluorescein was measured in rat aortic
      vascular smooth muscle cells cultured in the control, indigo carmine alone and
      tiron plus indigo carmine. RESULTS: Indigo carmine (10(-5) M) increased the
      phenylephrine-induced maximum contraction in the endothelium-intact rings with or
      without indomethacin, whereas indigo carmine produced a slight leftward shift in
      the phenylephrine concentration-response curves in the endothelium-denuded rings
      and L-NAME-pretreated endothelium-intact rings. In the endothelium-intact rings
      pretreated with tiron (10(-2) M), indigo carmine did not alter phenylephrine
      concentration-response curves significantly. Indigo carmine (10(-5) M) increased
      the fluorescence of oxidized dichlorofluorescein in the vascular smooth muscle
      cells, whereas tiron abolished the indigo carmine-induced increase in oxidized
      dichlorofluorescein fluorescence. CONCLUSIONS: Indigo carmine increases the
      phenylephrine-induced contraction mainly through an endothelium-dependent
      mechanism involving the inactivation of nitric oxide caused by the increased
      production of reactive oxygen species.

PMID- 21860753
TI  - Remifentanil alleviates transient cerebral ischemia-induced memory impairment
      through suppression of apoptotic neuronal cell death in gerbils.
AB  - BACKGROUND: During neurosurgical procedures, patients are often exposed to
      hypoxic and ischemic brain damage. Cerebral ischemia leads to neuronal cell death
      and eventually causes neurological impairments. Remifentanil is a new ultra-short
      acting phenylpiperidine opioid analgesic. In this study, we evaluated
      remifentanil to determine if it exerts an anti-apoptotic effect in the
      hippocampal dentate gyrus following transient global ischemia in gerbils.
      METHODS: Step-down avoidance task, terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL) assay, and immunohistochemical staining for
      caspase-3 were performed. RESULTS: The numbers of TUNEL-positive cells and
      caspase-3-positive cells in the dentate gyrus were increased by ransient global
      ischemia. Latency in the step-down avoidance task was increased by transient
      global ischemia. Results revealed that apoptotic cell death in the dentate gyrus
      was increased significantly following transient global ischemia, resulting in
      memory impairment. However, treatment with remifentanil suppressed ischemia
      induced apoptosis in the dentate gyrus, thereby alleviating the memory impairment
      that was induced by ischemic cerebral injury. CONCLUSIONS: These results indicate
      that remifentanil may exert a neuroprotective effect on ischemic brain damage
      during surgery.

PMID- 21860754
TI  - Morphine-induced postconditioning modulates mitochondrial permeability transition
      pore opening via delta-1 opioid receptors activation in isolated rat hearts.
AB  - BACKGROUND: It is generally accepted that morphine affords cardioprotection
      against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability
      transition pore (MPTP) is considered an end target for cardioprotection. The aim
      of this study was to investigate the involvement of opioid receptors (OR) and
      MPTP in morphine-induced postconditioning (M-Post). METHODS: Isolated rat hearts
      were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were
      treated with 1 uM morphine, with or without the OR antagonists or a MPTP opener
      at early reperfusion. Infarct size was measured with 2,3,5-triphenyltetrazolium
      chloride staining. RESULTS: There were no significant differences in
      cardiodynamic variables except a decrease in heart rate in the M-Post group (P <
      0.01 vs. control) after reperfusion. M-Post dramatically reduced infarct-risk
      volume ratio (9.8 +/- 2.5%, P < 0.001 vs. 30.0 +/- 3.7% in control). This
      beneficial effect on infarct volume by M-Post was comparable with ischemic
      postconditioning (11.9 +/- 2.2%, P > 0.05). The nonspecific OR antagonist
      naloxone (25.7 +/- 1.9%, P < 0.01), the delta-OR antagonist naltrindole (27.8 +/-
      4.3%, P < 0.05) and delta(1)-OR antagonist 7-benzylidenenaltrexone (24.7 +/-
      3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post. In addition,
      the anti-infarct effect by M-Post was also totally blocked by the MPTP opener
      atractyloside (26.3 +/- 5.2%, P < 0.05). CONCLUSIONS: M-Post effectively reduces
      myocardial infarction. The anti-infarct effect by M-Post is mediated via
      activation of delta-OR, especially delta(1)-OR, and inhibition of the MPTP
      opening.

PMID- 21860755
TI  - Acute-on-chronic subdural hematoma by spinal anesthesia in a patient with
      undiagnosed chronic subdural hematoma -A case report-.
AB  - Subdural hematoma is a serious but rare complication of spinal anesthesia. A 70
      year-old woman patient underwent elective total knee replacement under spinal
      anesthesia. At 4 days postoperatively, the patient complained of headache and
      vomiting. Brain computed tomography revealed an acute-on-chronic subdural
      hematoma with midline shift. The patient recovered completely after surgical
      decompression. We report a patient with an undiagnosed chronic subdural hematoma,
      who developed acute-on-chronic subdural hematoma after spinal anesthesia.

PMID- 21860756
TI  - Radiofrequency thermocoagulation of the thoracic splanchnic nerve in functional
      abdominal pain syndrome -A case report-.
AB  - The thoracic splanchnic nerve block has been used in managing abdominal pain,
      especially for pains arising from abdominal cancers. A 27-year-old male patient
      who had a constant abdominal pain was referred to our clinic for pain management
      but had no organic disease. The numeric rating scale (NRS) for pain scored 7/10.
      We applied a diagnostic thoracic splanchnic nerve block under the diagnosis of
      functional abdominal pain syndrome. Since the block reduced the pain, we applied
      a radiofrequency thermocoagulation at the T11 and T12 vertebral level.
      Thereafter, his symptoms improved markedly with pain decreasing to an NRS score
      of 2-3/10. Hereby, we report a successful management of functional abdominal pain
      via radiofrequency thermocoagulation of the thoracic splanchnic nerves.

PMID- 21860757
TI  - Anesthetic management of a patient with Mounier-Kuhn syndrome undergoing off-pump
      coronary artery bypass graft surgery -A case report-.
AB  - Mounier-Kuhn-syndrome patients have markedly dilated trachea and main bronchi due
      to an atrophy or absence of elastic fibers and thinning of smooth muscle layers
      in the tracheobronchial tree. Although this syndrome is rare, airway management
      is challenging and general anesthesia may produce fatal results. However, only a
      few cases have been reported and this condition is not widely known among
      anesthesiologists. We present the case of a tracheobronchomegaly patient
      undergoing an emergency off-pump coronary artery bypass. Although the trachea was
      markedly dilated with numerous tracheal diverticuli, there was an undilated 2 cm
      portion below the vocal cords found on the preoperative CT. Under a preparation
      of extracorporeal membrane oxygenation, we intubated and placed the balloon of an
      endotracheal tube (I.D. 9 mm) at this portion, and maintained ventilation during
      the operation. This case showed that a precise preoperative evaluation and
      anesthetic plan is essential for successful anesthetic management.

PMID- 21860758
TI  - LMA with positive pressure ventilation is safe!

PMID- 21860759
TI  - Occurrence of complete atrioventricular block during surgery.

PMID- 21860760
TI  - Audiovisual stimulation with synchronized pulsed tones and flickering lights set
      at a delta frequency can induce a sedative effect.

PMID- 21860761
TI  - A direct tying loop of silk sutures on the electrode.

PMID- 21860763
TI  - Does radical cystectomy improve overall survival in octogenarians with muscle
      invasive bladder cancer?
AB  - PURPOSE: We compared the efficacy of radical cystectomy (RC) and non-RC treatment
      [transurethral resection of bladder tumor (TURB) only, partial cystectomy, or
      TURB followed by radiotherapy] in octogenarians with muscle-invasive bladder
      cancer (MIBC). MATERIALS AND METHODS: A total of 177 patients aged 80 years or
      more underwent TURB at our institute, and 41 patients had MIBC according to the
      histologic examination. Fourteen patients with lymph node or distant metastasis
      were excluded, and 27 patients were ultimately included. Patients were stratified
      by treatment modality (RC vs. non-RC), Charlson Comorbidity Index (low CCI vs.
      high CCI), and clinical tumor stage (organ-confined disease vs. extravesical
      disease). The effects of several variables on cancer-specific and overall
      survival were assessed. RESULTS: Of the 27 patients, 11 (41%) underwent RC and 16
      (59%) underwent non-RC treatment. Patients in the RC group were younger and more
      likely to have low CCI scores. There were no significant differences in overall
      or cancer-specific survival in the RC and non-RC groups. Patients with clinically
      organ-confined disease had better survival outcomes than did those with
      extravesical disease. Stratification of patients by CCI indicated that overall
      survival was better in patients with low CCI scores (p=0.013), although cancer
      specific survival was similar in the two CCI groups. Univariate and multivariate
      analysis indicated that clinical tumor stage and CCI were independently
      associated with overall survival. CONCLUSIONS: RC in octogenarians with MIBC does
      not improve overall survival compared with other treatment modalities. However,
      clinically organ-confined disease and low CCI score were associated with better
      overall survival.

PMID- 21860762
TI  - Role of pelvic lymph node dissection in prostate cancer treatment.
AB  - Pelvic lymph node dissection (PLND) is the most accurate and reliable staging
      procedure for detecting lymph node invasion (LNI) in prostate cancer. Recently,
      [(11)C]-choline positron emission tomography imaging and magnetic resonance
      imaging with lymphotropic superpara-magnetic nanoparticles have shown potential
      for detecting LNI but are still under investigation. The risk of LNI in low-risk
      groups could be underestimated by use of the current nomograms, which rely on
      data collected from patients who underwent only limited PLND. Extended PLND
      (ePLND) shows higher lymph node yield, which leads to the removal of more
      positive nodes and fewer missed positive nodes. It may be possible to refrain
      from performing PLND on low-risk patients with a prostate-specific antigen value
      <10 ng/ml and a biopsy Gleason score <=6, but the risk of biopsy-related
      understaging should be kept in mind. Theoretically, meticulous ePLND may also
      impact prostate cancer survival by clearing low-volume diseases and occult
      micrometastasis even in pN0. The therapeutic role of PLND in prostate cancer
      patients is still an open question, especially in individuals with low-risk
      disease. Patients with intermediate- to high-risk disease are more likely to
      benefit from ePLND.

PMID- 21860764
TI  - Effect of Oral Administration of Acetaminophen and Topical Application of EMLA on
      Pain during Transrectal Ultrasound-Guided Prostate Biopsy.
AB  - PURPOSE: Transrectal ultrasound-guided prostate biopsy is the procedure of choice
      for diagnosing prostate cancer. We compared with pain-relieving effect of
      acetaminophen, a known drug for enhancing the pain-relieving effect of tramadol,
      and eutectic mixture of local anesthetics (EMLA), a local anesthetic agent, with
      that of the conventional periprostatic nerve block method. MATERIALS AND METHODS:
      This was a prospective, randomized, single-blinded study. A total of 430 patients
      were randomly assigned to three groups. Group 1 received a periprostatic nerve
      block with 1% lidocaine, group 2 received acetaminophen 650 mg, and group 3
      received EMLA cream for pain control. All patients were given 50 mg of tramadol
      intravenously 30 minutes before the procedure. At 3 hours after completion of the
      procedure, the patients were asked to grade their pain on a horizontal visual
      analogue scale (VAS). The patients were also asked whether they were willing to
      undergo future biopsy if required. RESULTS: There were no significant differences
      between the three groups in terms of age, prostate-specific antigen, prostate
      size, or numbers of biopsy cores. The pain scores for groups 2 and group 3, which
      were 3.47+/-1.92 and 3.50+/-1.36, respectively, were similar and were
      significantly lower than that of group 1, which was 5.24+/-2.07. CONCLUSIONS:
      Acetaminophen and EMLA cream with intravenous injection of tramadol are safe,
      easy, and effective methods of controlling pain during the procedure. These
      methods were more effective for pain relief than was the conventional
      periprostatic nerve block method.

PMID- 21860765
TI  - Prostate Cancer Can Be Detected Even in Patients with Decreased PSA Less than 2.5
      ng/ml after Treatment of Chronic Prostatitis.
AB  - PURPOSE: We evaluated men with documented chronic prostatitis and elevated serum
      prostate-specific antigen (PSA) to determine whether treatment with antibiotics
      and anti-inflammatory drugs can lower serum PSA and the cancer detection rate in
      patients with post-treatment PSA <4 ng/ml. MATERIALS AND METHODS: Eighty-six men
      who presented with serum PSA greater than 4 ng/ml and who were subsequently
      diagnosed with chronic prostatitis with greater than 10 white blood cells per
      high power field in expressed prostatic excretions were included in this
      prospective study. Patients meeting these criteria underwent treatment with a 4
      week course of antibiotics and nonsteroidal anti-inflammatory agents. Follow-up
      PSA and transrectal ultrasonography-guided prostate biopsy were performed within
      2 months of treatment for all patients. RESULTS: Mean patient age was 56.2 years
      (range, 37-72 years). Mean PSA (ng/ml) decreased by 33.8%, from 8.12 (range, 4.02
      24.8) to 5.37 (range, 1.35-12.94), after treatment (p=0.001). Pathological
      studies revealed prostate cancer in 18 cases (20.9%), chronic inflammation in 64
      (74.4%), and benign prostatic hypertrophy in 4 (4.7%). The prostate cancer
      detection rate according to the follow-up PSA level, below 2.5, from 2.5 to 4.0,
      and above 4.0, was 13.3% (2/15), 13.6% (3/22), and 26.5% (13/49), respectively.
      CONCLUSIONS: When chronic prostatitis with elevated PSA is identified, antibiotic
      and anti-inflammatory treatment can lower these PSA levels. However, the
      possibility of prostate cancer remains in patients whose PSA level decreases to
      less than 4 ng/ml, even in those with a PSA level less than 2.5 ng/ml.

PMID- 21860766
TI  - Efficacy of alternative antiandrogen therapy for prostate cancer that relapsed
      after initial maximum androgen blockade.
AB  - PURPOSE: We evaluated the effectiveness of second-line maximum androgen blockade
      (MAB) with an alternative antiandrogen in patients who relapsed after initial
      MAB. MATERIALS AND METHODS: We retrospectively analyzed 47 patients with prostate
      cancer who relapsed after initial MAB, including surgical or medical castration
      combined with antiandrogens, from January 1998 to December 2009. When the serum
      prostate-specific antigen (PSA) level was increased on three consecutive
      occasions, we discontinued the antiandrogen and then administered an alternative
      antiandrogen. Seven patients were assessed for antiandrogen withdrawal syndrome
      (AWS). The effect of the second-line MAB was evaluated by the serum PSA level,
      and response was subdivided into >=50% and <50% PSA reductions from the baseline
      PSA at the start of second-line MAB. RESULTS: PSA reduction was observed in 32
      patients (68.1%). Among them, 23 (48.9%) achieved >=50% PSA reductions with a
      mean response duration of 13.4+/-5.4 months. Nine (19.2%) patients reached <50%
      PSA reductions with a mean response duration of 12.2+/-6.2 months. The time to
      nadir PSA level after first-line MAB in the >=50% PSA reduction group, <50% PSA
      reduction group, and PSA elevation group was 15.6+/-12.9 months, 11.8+/-6.0
      months, and 8+/-6.5 months, respectively. That is to say, it was significantly
      longer in the responder groups (p=0.038). CONCLUSIONS: Second-line MAB using an
      alternative antiandrogen is an effective treatment option before cytotoxic
      chemotherapy in patients who relapse after initial MAB.

PMID- 21860768
TI  - Laparoscopic versus Open Radical Nephrectomy in T2 Renal Cell Carcinoma: Long
      Term Oncologic Outcomes.
AB  - PURPOSE: Laparoscopic radical nephrectomy (LRN) has become the standard technique
      for radical nephrectomies for T1 renal tumors (7 cm or less). We extended our
      experience with LRN to T2 renal tumors (greater than 7 cm) and compared the
      efficacy and long-term oncologic outcomes with those of open radical nephrectomy
      (ORN) for T2 clear renal cell carcinoma (RCC) in the same period. MATERIALS AND
      METHODS: We retrospectively analyzed the data from 33 patients who underwent LRN
      and 35 patients who underwent ORN in our institution from January 2003 to June
      2006 for T2N0M0 RCC. We compared long-term oncologic outcomes between the two
      groups. RESULTS: The median follow-up periods were 60.0 months (range, 48.0-77.0
      months) and 65.6 months (range, 56.0-77.0 months) in the LRN and ORN groups,
      respectively. There were no statistically significant differences between the two
      groups in the patients' demographic data. There were no significant differences
      in the 5-year overall survival rate, the cancer-specific survival rate, or the
      recurrence-free survival rate. CONCLUSIONS: Our results suggest that LRN for the
      management of T2 RCC is feasible and efficacious and that the long-term oncologic
      outcomes of LRN are comparable to those of ORN.

PMID- 21860767
TI  - Role of the mTOR Pathway in the Progression and Recurrence of Bladder Cancer: An
      Immunohistochemical Tissue Microarray Study.
AB  - PURPOSE: Numerous trials have been conducted to develop new treatment regimens
      for superficial and invasive bladder cancer, because there is an urgent need to
      identify novel agents to prevent the recurrence and progression of these cancers.
      We evaluated the prognostic and biological significance of mTOR pathway-related
      markers in patients with bladder cancer who had undergone transurethral resection
      of their bladder tumors and radical cystectomy. MATERIALS AND METHODS: We
      retrieved 208 bladder cancer specimens collected from patients between 1989 and
      2007 and constructed a tissue microarray comprising 208 tumor samples and 25
      benign urothelium samples. Immunohistochemical staining was performed for mTOR,
      phosphorylated (phos) S6, and phos4E-BP1. The pattern, percentage, and intensity
      of staining for all three markers were evaluated. RESULTS: The median age at
      diagnosis of the patient cohort was 67 years (range: 29-87 years), and the median
      follow-up was 72 months (range: 1-257 months). The expression of phos4E-BP1 was
      higher in the bladder cancer cohort than in the benign cohort, whereas phosS6
      expression was lower in the bladder cancer cohort than in the benign cohort. The
      expression of phosS6 was significantly higher in high-grade bladder cancer
      (p<0.01). There was a significant positive correlation between the H-scores of
      mTOR and phos4E-BP1 (coefficient of correlation, r=0.37, p<0.01) as well as
      between the H-scores of mTOR and phosS6 (r=0.17, p<0.05). In the multivariate
      analysis, strong phosS6 expression predicted shorter progression (p<0.01; hazard
      ratio [HR], 2.516) and disease-specific survival (p<0.01; HR, 2.396) but not
      overall survival (p=0.112), whereas strong phos4E-BP1 expression was a predictor
      of disease-specific survival (p<0.05; HR, 2.105). Moreover, strong phosS6
      expression predicted shorter recurrence-free (p<0.05) and progression-free
      (p<0.05) survival in the superficial bladder cancer cohort. CONCLUSIONS: Our
      results demonstrate that mTOR pathway activation, as assessed by phos4E-BP1
      phosphorylation, is related to bladder cancer tumorigenesis and that S6 protein
      phosphorylation is associated with a high level of disease recurrence and
      progression and poor cancer-specific survival.

PMID- 21860769
TI  - Efficacy and Tolerability of Tamsulosin 0.4 mg in Patients with Symptomatic
      Benign Prostatic Hyperplasia.
AB  - PURPOSE: To evaluate the efficacy and tolerability of tamsulosin 0.4 mg once
      daily in Korean patients with symptomatic benign prostatic hyperplasia (BPH) and
      investigate whether tamsulosin 0.4 mg can improve symptoms in patients with
      refractory lower urinary tract symptoms (LUTS) who were previously receiving
      tamsulosin 0.2 mg once daily. MATERIALS AND METHODS: A total of 116 patients from
      3 urology centers participated. All study subjects entered a nonblind phase
      consisting of 8 weeks of tamsulosin 0.2 mg monotherapy followed by an additional
      8 weeks of tamsulosin 0.2 mg (0.2 mg group) or 8 weeks of tamsulosin 0.4 mg (0.4
      mg group). At week 8, we chose the 0.4 mg group on the basis of International
      Prostate Symptom Score (IPSS), quality of life (QoL), maximal urinary flow rate
      (Qmax), and adverse effects. At week 16, we compared the efficacy and
      tolerability of tamsulosin between the 0.2 and 0.4 mg groups. RESULTS: A total of
      26 patients (22.4%) were escalated to tamsulosin 0.4 mg at week 8. There were
      significant differences in IPSS, QoL, and Qmax at week 8 in both groups. There
      were significant differences in improvement in IPSS, QoL, Qmax, and postvoid
      residual urine volume from baseline to week 16 in both groups. There were no
      significant differences in efficacy or tolerability between the groups at week
      16. CONCLUSIONS: Our trial demonstrated that tamsulosin 0.4 mg has favorable
      efficacy and tolerability in Korean patients with symptomatic BPH refractory to
      tamsulosin 0.2 mg. No patients experienced any serious adverse effects when we
      escalated the dose of tamsulosin to 0.4 mg.

PMID- 21860770
TI  - Effects of tamsulosin, solifenacin, and combination therapy for the treatment of
      ureteral stent related discomforts.
AB  - PURPOSE: To evaluate the effect of tamsulosin, solifenacin, and combination
      therapy of two agents in improving the lower urinary tract symptoms of patients
      with indwelling double-J ureteral stents. MATERIALS AND METHODS: A total of 168
      patients underwent placement of a double-J ureteral stent after retrograde
      ureteroscopy for urinary stone disease. All patients received polyurethane double
      J ureteral stents (6 Fr, 24 or 26 cm), which were removed a mean of 14 days
      postoperatively. A total of 48 patients were given no medication (Group 1), 43
      patients were given tamsulosin 0.2 mg once daily (Group 2), 45 patients were
      given solifenacin 5 mg once daily (Group 3), and 32 patients were given a
      combination of two agents postoperatively (Group 4). International Prostate
      Symptom Score/quality of life (IPSS/QoL) and visual analogue pain scale (VAPS)
      questionnaires were completed by each patient at 1 day postoperatively and on the
      day of stent removal. RESULTS: In the total group of patients, the mean age was
      50.24+/-12.90 years. There was a significant difference in the IPSS total score
      between group 1 and groups 3 and 4. Group 4 also differed significantly from
      group 1 in the irritative subscore. The obstructive subscore differed between
      groups 2 and 4 and group 1. There was a statistically significant difference
      between group 1 and group 4 in the QoL score. There were no significant
      differences in the VAPS. CONCLUSIONS: Combination therapy with tamsulosin and
      solifenacin improved both irritative and obstructive symptoms more than in the
      other groups. Combination therapy should be strongly considered for patients who
      complain of stent-related symptoms.

PMID- 21860771
TI  - Clinical characteristics and surgical outcomes in adolescents and adults with
      varicocele.
AB  - PURPOSE: To compare clinical characteristics and surgical results in adolescents
      and adults with varicocele. MATERIALS AND METHODS: We retrospectively analyzed
      the characteristics of 93 patients, 34 adolescents (mean age, 14.4+/-2.1 years)
      and 59 adults (mean age, 30.4+/-12.4 years), who underwent surgical repair of
      varicocele between 2006 and 2009. Median follow-up time in all patients was 18.7
      months. The most bothersome symptoms, bilaterality, grades, surgical methods,
      artery-sparing rates, operation times, semen analysis, success rates, and
      recurrence-free period were compared between the two groups. RESULTS: The overall
      success rate of surgical repair was 92.5%. The most bothersome symptoms were
      scrotal mass, pain, and hypotrophy in adolescents and pain, scrotal mass,
      infertility, and hypotrophy in adults (p=0.008). There were no significant
      between-group differences in bilaterality, grades, surgical methods, operation
      times, pre- or postoperative semen analyses, success rates, or recurrence-free
      periods. Patients who underwent artery-sparing surgery had higher recurrence
      rates than did those who underwent surgery that did not spare arteries. In
      adults, semen density increased significantly after surgery, from 35.6 million/ml
      to 49.6 million/ml (p=0.046). CONCLUSIONS: There were no significant differences
      in clinical characteristics or surgical results between adolescents and adults
      with varicocele, except for the most bothersome symptoms. Semen density increased
      after surgery in both groups.

PMID- 21860772
TI  - Limited expression of cytochrome p450 17alpha-hydroxylase/17,20-lyase in prostate
      cancer cell lines.
AB  - PURPOSE: Cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17A1) is a key
      enzyme in the androgen biosynthesis pathway. CYP17A1 has been focused on because
      of the promising results of a potent CYP17A1 inhibitor in the treatment of
      castration-resistant prostate cancer (CRPC). A hypothesis that intratumoral
      androgenesis may play a role in the progression of CRPC has recently been
      postulated. Thus, we evaluated whether commonly used prostate cancer cell lines
      express CYP17A1. MATERIALS AND METHODS: Androgen-sensitive LNCaP and androgen
      insensitive PC-3 and DU145 cells were used. To evaluate the expression of CYP17A1
      protein and RNA, we performed Western blotting and RT-PCR, respectively. RESULTS:
      We were unable to detect either CYP17A1 protein or RNA in any of the cell lines
      tested. We failed to detect any expression of CYP17A1, despite several
      repetitions of these techniques under different conditions. CONCLUSIONS: The
      expression of CYP17A1 protein and RNA in LNCaP, PC-3, and DU145 cells appears to
      be either absent or too low for detection. The mechanism of action of abiraterone
      acetate, a CYP17A1 inhibitor, may be related more to adrenal androgen blockade
      than to intratumoral androgenesis.

PMID- 21860773
TI  - Bilateral renal choriocarcinoma in a postmenopausal woman.
AB  - Choriocarcinoma is the most malignant tumor of gestational trophoblastic
      neoplasia. It grows rapidly and metastasizes to the lung, liver, and less
      frequently, the brain. Metastases to the kidney are rare in the literature, and
      bilateral involvement is even more scarce. Renal involvement of choriocarcinoma
      is highly exceptional and may mimic renal cell carcinoma. Here we report a case
      of bilateral renal choriocarcinoma presenting 5 years after a history of a total
      anterior hysterectomy because of a hydatidiform mole.

PMID- 21860774
TI  - Cystic dysplasia of the rete testis accompanying an inguinal hernia: a 63-year
      old man.
AB  - Cystic dysplasia of the rete testis (CDT) is a very rare congenital benign
      testicular tumor that is often associated with ipsilateral genitourinary
      anomalies. It is usually found in the pediatric population and must be
      differentially diagnosed from a malignant lesion. Here we report the case of a 63
      year-old man with a left inguinal hernia who visited our urologic outpatient
      clinic. Scrotal ultrasonography showed a left direct inguinal hernia in the
      inguinal area and a well-circumscribed cystic lesion containing multiple minute
      cysts with echogenic foci occupying almost one-third of the left testicular
      parenchyma. Testicular tumor markers were within the normal range and a computed
      tomography scan of the abdomen showed no genitourinary abnormalities. We presumed
      that the left testicular lesion was malignant, and the patient underwent radical
      orchiectomy. However, the pathologic examination revealed a CDT. Here we present
      this case of a 63-year-old man with an inguinal hernia accompanied by multiple
      cystic lesions on the left testis.

PMID- 21860775
TI  - Alterations along the Hypothalamic-Pituitary-Thyroid Axis of the Zebrafish (Danio
      rerio) after Exposure to Propylthiouracil.
AB  - In the past, various approaches have been developed to detect adverse effects of
      pollutants on the thyroid of vertebrates, most of these with special emphasis on
      the South African clawed frog, Xenopus laevis. Although fish are primarily
      affected by thyroid-disrupting chemicals, studies into alterations of the thyroid
      of fish are scarce. Therefore, effects of the reference compound propylthiouracil
      on histopathology of the thyroid axis were analyzed in a modified early life
      stage test with zebrafish (Danio rerio) exposed to propylthiouracil. The test
      substance induced dose-dependent alterations of thyroidal tissue concomitant with
      increases in the number of surrounding blood vessels. Despite this massive
      proliferation of the thyroid, zebrafish were not able to maintain thyroxin
      concentrations. The pituitary was affected displaying significant alterations in
      thyroid-stimulating hormone cell counts. Quantitative evaluation of pituitary
      surface areas revealed a dose-dependent increase of adenohypophyseal tissue.
      Distinct histopathological effects may contribute to a more easy identification
      and interpretation of alterations induced by thyroid-disrupting chemicals.

PMID- 21860776
TI  - The evaluation of diastolic dysfunction with tissue Doppler echocardiography in
      women with subclinical hypothyroidism and the effect of L-thyroxine treatment on
      diastolic dysfunction: a pilot study.
AB  - Background. Subclinical hypothyroidism (SH) predominantly affects women. The
      necessity of treatment in SH is controversial. Objective. We aimed to investigate
      the response of diastolic dysfunction to thyroid hormone replacement therapy
      (THRT) in women. Methods and Results. Twenty-two female subjects with SH and 20
      euthyroid female controls were enrolled. Baseline and follow-up biochemical,
      hormonal, and echocardiographic evaluations were performed. Repeat
      echocardiograms were performed three months after the achievement of a euthyroid
      status with THRT. Mean baseline myocardial performance index (MPI) was 0.27 +/-
      0.08 in the SH group, and 0.22 +/- 0.06 in the control group (P = 0.03). MPI did
      not change significantly after THRT. Pulsed-wave Doppler findings were not
      different among the groups. However, tissue Doppler-derived mitral annular E'
      velocities were significantly lower in the SH group. A moderate but significant
      improvement was observed in E' velocities after THRT (13.2 +/- 3.87 versus 14.53
      +/- 2.75, P = 0.04). We also observed left ventricular concentric remodeling in
      SH patients which was reversible with THRT. Conclusions. Tissue Doppler
      echocardiography may be a useful tool for monitoring the response of diastolic
      dysfunction to thyroid hormone replacement therapy in patients with SH. Our
      findings suggest that THRT may reverse diastolic dysfunction in women with SH.

PMID- 21860777
TI  - High-level language production in Parkinson's disease: a review.
AB  - This paper discusses impairments of high-level, complex language production in
      Parkinson's disease (PD), defined as sentence and discourse production, and
      situates these impairments within the framework of current psycholinguistic
      theories of language production. The paper comprises three major sections, an
      overview of the effects of PD on the brain and cognition, a review of the
      literature on language production in PD, and a discussion of the stages of the
      language production process that are impaired in PD. Overall, the literature
      converges on a few common characteristics of language production in PD: reduced
      information content, impaired grammaticality, disrupted fluency, and reduced
      syntactic complexity. Many studies also document the strong impact of differences
      in cognitive ability on language production. Based on the data, PD affects all
      stages of language production including conceptualization and functional and
      positional processing. Furthermore, impairments at all stages appear to be
      exacerbated by impairments in cognitive abilities.

PMID- 21860778
TI  - Development of a non-motor fluctuation assessment instrument for Parkinson
      disease.
AB  - Patients with Parkinson disease are increasingly recognized to suffer from non
      motor symptoms in addition to motor symptoms. Many non-motor symptoms fluctuate
      in parallel with motor symptoms and in relationship to plasma levodopa levels.
      Though these symptoms are troublesome and result in reduced quality of life to
      patients and their caregivers, there has not been an objective method of
      recognizing and quantifying non-motor fluctuations (NMFs). This study sought to
      develop a patient-based instrument that would accurately capture the experience
      of patients with NMFs. Patient-based nominal group technique sessions, focus
      groups, and expert opinion were utilized in developing this questionnaire.

PMID- 21860779
TI  - Genetic mutations and mitochondrial toxins shed new light on the pathogenesis of
      Parkinson's disease.
AB  - The cellular abnormalities in Parkinson's disease (PD) include mitochondrial
      dysfunction and oxidative damage, which are probably induced by both genetic
      predisposition and environmental factors. Mitochondrial dysfunction has long been
      implicated in the pathogenesis of PD. The recent discovery of genes associated
      with the etiology of familial PD has emphasized the role of mitochondrial
      dysfunction in PD. The discovery and increasing knowledge of the function of
      PINK1 and parkin, which are associated with the mitochondria, have also enhanced
      the understanding of cellular functions. The PINK1-parkin pathway is associated
      with quality control of the mitochondria, as determined in cultured cells treated
      with the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP),
      which causes mitochondrial depolarization. To date, the use of mitochondrial
      toxins, for example, 1-methyl-4-phynyl-tetrahydropyridine (MPTP) and CCCP, has
      contributed to our understanding of PD. We review how these toxins and familial
      PD gene products are associated with and have enhanced our understanding of the
      role of mitochondrial dysfunction in PD.

PMID- 21860780
TI  - Spectral domain optical coherence tomography in diffuse unilateral subacute
      neuroretinitis.
AB  - Purpose. To describe the SD-OCT findings in patients with diffuse unilateral
      subacute neuroretinitis (DUSN) and evaluate CRT and RNFL thickness. Methods.
      Patients with clinical diagnosis of DUSN who were submitted to SD-OCT were
      included in the study. Complete ophthalmologic examination and SD-OCT were
      performed. Cirrus scan strategy protocols used were 200 * 200 macular cube, optic
      nerve head cube, and HD-5 line raster. Results. Eight patients with DUSN were
      included. Mean RNFL thickness was 80.25 MUm and 104.75 MUm for affected and
      normal eyes, respectively. Late stage had mean RNFL thickness of 74.83 MUm
      compared to 96.5 MUm in early stage. Mean CMT was 205.5 MUm for affected eyes and
      255.13 MUm for normal fellow eyes. Conclusion. RNFL and CMT were thinner in DUSN
      eyes compared to normal eyes. Late-stage disease had more pronounced thinning
      compared to early-stage patients. This thinning in RNFL and CMT may reflect the
      low visual acuity in patients with DUSN.

PMID- 21860781
TI  - Control of aptamer function using radiofrequency magnetic field.
AB  - Remote control of aptamer function has allowed us to control protein function in
      space and time. Here, we propose a novel control system for aptamer function by
      radiofrequency magnetic field- (RFMF-) induced local heating of a gold
      nanoparticle conjugated with an aptamer. In this study, we used a 31-mer thrombin
      binding aptamer (TBA), which can inhibit thrombin activity, as a model aptamer.
      We evaluated the RFMF control of the inhibitory activity of a gold nanoparticle
      conjugated TBA. To evaluate the effect of RFMF on enzymatic activity, we utilized
      a complementary DNA strand that maintains the broken structure during the
      activity assay. We observed a decrease in the inhibitory activity of TBA after
      RFMF irradiation. It indicates that RFMF is capable of controlling the TBA
      structure. Because RFMF allows noninvasive control of aptamer function, this
      strategy is expected to be novel way of controlling aptamer drug activity.

PMID- 21860782
TI  - Radiolytic reduction characteristics of artificial oligodeoxynucleotides
      possessing 2-oxoalkyl group or disulfide bonds.
AB  - A number of advances have been made in the development of modified
      oligodeoxynucleotides (ODNs), and chemical or physical properties of which are
      controlled by external stimuli. These intelligent ODNs are promising for the next
      generation of gene diagnostics and therapy. This paper focuses on the molecular
      design of artificial ODNs that are activated by X-irradiation and their
      applications to regulation of hybridization properties, conformation change,
      radiation-activated DNAzyme, and decoy molecules.

PMID- 21860783
TI  - Knowledge and Practice of PHC Physicians toward the Detection and Management of
      Hypertension and Other CVD Risk Factors in Egypt.
AB  - Aim. To assess the knowledge and practice of PHC physicians toward the detection
      and management of hypertension (HTN) and other CVD risk factors. Methods. A cross
      sectional study of all primary health care physicians of the FHU of three rural
      districts of Egypt was conducted. Each physician was subjected to a prevalidated
      interview questionnaire on the WHO-CVD risk management package for low and medium
      resources, and a checklist of observation of daily practices. Results.
      Hypertension was a priority problem in about two-thirds (62.9%) of physicians,
      yet only 19% have guidelines for HTN patients. Clinical history recording system
      for HNT was available for 50% of physicians. Levels of knowledge varied with
      regard to definition of HTN (61.3%, fair), procedures for BP measurement (43.5%,
      poor), indications for referral (43.5%, poor), patient counseling (61.3%, fair),
      patient treatment (59.8%, fair). Availability of clinical history recording
      system for HNT was a significant predictor for physician's level of knowledge (P
      = 0.001). Overall level of practice was fair (68.5%). Conclusion. PHC physicians
      have unsatisfactory knowledge and practice on hypertension. There is a need of
      more continuing medical education. Local and international manuals, workshops,
      and seminars on how to make use of these guidelines would improve doctors'
      performance.

PMID- 21860784
TI  - Thymoma in myasthenia gravis: from diagnosis to treatment.
AB  - One half of cortical thymoma patients develop myasthenia gravis (MG), while 15%
      of MG patients have thymomas. MG is a neuromuscular junction disease caused in
      85% of the cases by acetylcholine receptor (AChR) antibodies. Titin and ryanodine
      receptor (RyR) antibodies are found in 95% of thymoma MG and 50% of late-onset MG
      (MG onset >=50 years), are associated with severe disease, and may predict
      thymoma MG outcome. Nonlimb symptom profile at MG onset with bulbar, ocular,
      neck, and respiratory symptoms should raise the suspicion about the presence of
      thymoma in MG. The presence of titin and RyR antibodies in an MG patient younger
      than 60 years strongly suggests a thymoma, while their absence at any age
      strongly excludes thymoma. Thymoma should be removed surgically. Prethymectomy
      plasmapheresis/iv-IgG should be considered before thymectomy. The pharmacological
      treatment does not differ from nonthymoma MG, except for tacrolimus which is an
      option in difficult thymoma and nonthymoma MG cases with RyR antibodies.

PMID- 21860785
TI  - Effects of exercise training on molecular markers of lipogenesis and lipid
      partitioning in fructose-induced liver fat accumulation.
AB  - The present study was designed to investigate the impact of exercise training on
      lipogenic gene expression in liver and lipid partitioning following the ingestion
      of a high fructose load. Female rats were exercise-trained for 8 wk or kept
      sedentary before being submitted to a fasting/refeeding protocol. Rats were
      further subdivided as follow: rats were fasted for 24 h, refed a standard diet
      for 24 h, starved for another 24 h, and refed with a standard or a high-fructose
      diet 24 h before sacrifice. Fructose refeeding was associated with an increase in
      hepatic lipid content, endocannabinoid receptor 1, sterol regulatory element
      binding protein1c, and stearoyl-CoA desaturase1 gene expression in both Sed and
      TR rats. However, desaturation indexes measured in liver (C16 : 1/C16 : 0 and C18
      : 1/C18 : 0) and plasma (C18 : 1/C18 : 0) were higher (P < 0.01) in TR than in
      Sed rats following fructose refeeding. It is concluded that exercise training
      does not significantly affect fat accumulation and the molecular expression of
      genes involved in lipogenesis after fasting and fructose refeeding but does
      modify the partitioning of lipids so as to provide more unsaturated fatty acids
      in liver without affecting liver fat content.

PMID- 21860786
TI  - Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in
      Malaysia.
AB  - HIV-infected prisoners in Malaysia represent a critical target population for
      secondary HIV risk reduction interventions and care. We report on the process and
      outcome of our formative research aimed at systematically selecting and adapting
      an EBI designed to reduce secondary HIV risk and improve adherence to
      antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our
      formative work involved a critical examination of established EBIs and associated
      published reports complemented by data elicited through structured interviews and
      focus groups with key stakeholders, members of the target population, and their
      family members. Based on all information, we adapted the Holistic Health Recovery
      Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2
      hour sessions that cover a range of specified topics so that participants may
      individually apply intervention content as needed to accommodate their particular
      substance abuse, HIV risk, and antiretroviral adherence issues. This study
      provides a complete example of the process of selecting and adapting an EBI
      taking into account both empirical evidence and input from target organization
      stakeholders and target population members and their families-for use in real
      world prison settings where high-risk populations are concentrated.

PMID- 21860788
TI  - Frequency of anemia in the patients of a family health team in dourados, mato
      grosso do sul, Brazil.
AB  - Anemia is a clinical manifestation with high prevalence in the world, reaching
      about 30% of the total inhabitants of the planet. It is responsible for a great
      reduction in quality of life of affected people. The present paper aimed to
      obtain the frequency of anemia in the blood counts of a sample from the
      population of registered patients of a Family Health Team in Dourados, MS,
      Brazil. 462 patients, who had blood counts done from February 2008 to March 2009,
      were included in this research. The frequency of anemia was 22.7% in the studied
      population, including all age groups.

PMID- 21860787
TI  - Nephrotoxicity of HAART.
AB  - Highly active antiretroviral therapy (HAART) and other medical therapies for HIV
      related infections have been associated with toxicities. Antiretroviral therapy
      can contribute to renal dysfunction directly by inducing acute tubular necrosis,
      acute interstitial nephritis, crystal nephropathy, and renal tubular disorders or
      indirectly via drug interactions. With the increase in HAART use, clinicians must
      screen patients for the development of kidney disease especially if the regimen
      employed increases risk of kidney injury. It is also important that patients with
      chronic kidney disease (CKD) are not denied the best combinations, especially
      since most drugs can be adjusted based on the estimated GFR. Early detection of
      risk factors, systematic screening for chronic causes of CKD, and appropriate
      referrals for kidney disease management should be advocated for improved patient
      care. The interaction between immunosuppressive therapy and HAART in patients
      with kidney transplants and the recent endorsement of tenofovir/emtricitabine by
      the Centers for Disease Control (CDC) for preexposure prophylaxis bring a new
      dimension for nephrotoxicity vigilance. This paper summarizes the common
      antiretroviral drugs associated with nephrotoxicity with particular emphasis on
      tenofovir and protease inhibitors, their risk factors, and management as well as
      prevention strategies.

PMID- 21860789
TI  - The Relationship between Personality and Depression in Expectant Parents.
AB  - Several studies assessed the relationship between depression and dimensions of
      temperament/character using the Cloninger's model of personality and the TCI-R.
      The aim of this study is clarify the relation between depression and personality
      in men and women who are expecting a baby. The Temperament and Character
      Inventory-Revised Form and the Beck Depression Inventory were administered to 65
      pregnant women and 37 husbands during the last quarter of pregnancy. ANOVAs
      showed that pregnant women had higher levels of depression, reward dependence,
      and self-transcendence than the expectant fathers. Hierarchical Multiple
      Regression Analysis in the pregnant women group showed that harm avoidance and
      self-directedness were significant predictors of the level of depression. In the
      expectant fathers, only self-directedness was a significant predictor of
      depression. Low TCI-R self-directedness is a strong predictor of depression in
      expectant parents during pregnancy regardless of gender, and high TCI-R harm
      avoidance is an additional predictor of depression in expectant mothers.

PMID- 21860790
TI  - Health-related conditions and depression in elderly mexican american and non
      Hispanic white residents of a United States-Mexico border county: moderating
      effects of educational attainment.
AB  - We investigated the prevalence of "high" levels of depressive symptomatology and
      13 health-related medical conditions in elderly Mexican American (MA) and non
      Hispanic white (NHW) residents of El Paso County, Texas. We analyzed the extent
      to which depressive symptoms in this population are associated with these
      conditions. Elderly MA residents possessed a higher prevalence of current
      depression, a relatively unique health-related condition profile, and were more
      likely to experience a set of conditions that impede participation in daily life
      conditions that we found to be strongly associated with high depressive
      symptomatology in the elderly. After adjusting for educational attainment, using
      multiple regression analyses, depression was not associated with ethnicity and
      only six of the health related conditions showed significant differences between
      MA and NHW subjects. We believe these results provide an important insight into
      the mechanism of health-related conditions and depressive symptomatology in a
      large sample of elderly MAs; and how conditions typically attributed to MA
      ethnicity may in actuality be an artifact of socioeconomic status variables such
      as educational-attainment.

PMID- 21860791
TI  - A pilot study of quantitative MRI measurements of ventricular volume and cortical
      atrophy for the differential diagnosis of normal pressure hydrocephalus.
AB  - Current radiologic diagnosis of normal pressure hydrocephalus (NPH) requires a
      subjective judgment of whether lateral ventricular enlargement is
      disproportionate to cerebral atrophy based on visual inspection of brain images.
      We investigated whether quantitative measurements of lateral ventricular volume
      and total cortical thickness (a correlate of cerebral atrophy) could be used to
      more objectively distinguish NPH from normal controls (NC), Alzheimer's (AD), and
      Parkinson's disease (PD). Volumetric MRIs were obtained prospectively from
      patients with NPH (n = 5), PD (n = 5), and NC (5). Additional NC (n = 5) and AD
      patients (n = 10) from the ADNI cohort were examined. Although mean ventricular
      volume was significantly greater in the NPH group than all others, the range of
      values overlapped those of the AD group. Individuals with NPH could be better
      distinguished when ventricular volume and total cortical thickness were
      considered in combination. This pilot study suggests that volumetric MRI
      measurements hold promise for improving NPH differential diagnosis.

PMID- 21860792
TI  - Posterior urethral valves: renal failure and prenatal treatment.
AB  - Posterior urethral valves occur in 1 : 5000 live births. Despite the high
      prevalence, the few children that survive do poorly, with over 50% progressing to
      ESRD in 10 years. The gold standard for post-natal diagnosis is voiding
      cystourethrography, while pre-natal diagnosis is dependent on routine screening
      ultrasonography. Despite the ability to identify features of bladder outlet
      obstruction early in fetal development, there is no consensus on how to
      incorporate early detection into current screening protocols. There has yet to be
      a marker that allows prediction of obstruction in the absence of or prior to
      radiographic evidence of obstruction. With our current screening strategy, the
      majority of interventions are performed well after irreversible damage has
      occurred. Improved mortality and long term morbidity from posterior urethral
      valves and congenital bladder outlet obstruction will likely remain unchanged
      until it is possible to intervene prior to the onset of irreversible renal
      damage. New biologic markers and improved instrumentation will allow for more
      effective diagnosis and intervention at earlier stages of fetal development.

PMID- 21860793
TI  - Urinary angiotensinogen as a biomarker of nephropathy in childhood.
AB  - While most circulating angiotensinogen (AGT) is synthesized in the liver, the
      kidneys also produce AGT. Recently, we reported that urinary AGT is mainly
      originated from AGT. Using newly developed human AGT ELISA, we measured urinary
      AGT levels in chronic glomerulonephritis (GN) patients and patients with type 1
      diabetes in childhood. Urinary AGT level was positively correlated with diastolic
      blood pressure, urinary albumin, urinary protein levels, and urinary occult blood
      in chronic GN patients. Furthermore, urinary AGT level was significantly
      increased in chronic GN patients not treated with renin-angiotensin system (RAS)
      blockers compared with control subjects. Importantly, patients treated with RAS
      blockers had a marked attenuation of this increase. Also, urinary AGT level was
      significantly higher in patients with diabetic nephropathy in the
      premicroalbuminuric phase than in control subjects. These results suggest that
      urinary AGT reflects intrarenal RAS status in chronic GN and may be an early
      marker of diabetic nephropathy.

PMID- 21860794
TI  - Fibroblast growth factor 23 predicts left ventricular mass and induces cell
      adhesion molecule formation.
AB  - Elevated FGF-23 is a predictor of mortality and is associated with LVH in CKD. It
      may be a biomarker or a direct toxin. We assessed the relationship between FGF-23
      and LVH in CKD using CMRI. In vitro we studied the effect of phosphate, FGF-23,
      and Klotho on E-selectin and VCAM production in HUVECs. FGF-23 concentration
      correlates negatively with eGFR and positively with LVMI. FGF-23 was an
      independent predictor of LVH in CKD. E-selectin and VCAM production was elevated
      in HUVECs cultured in high phosphate with FGF-23 or Klotho. This effect was
      attenuated in cells exposed to both FGF-23 and Klotho. FGF-23 is an independent
      predictor of LVH as measured by CMRI. We show preliminary data which supports
      that FGF-23 is toxic resulting in activation of the vascular endothelium. We do
      not prove causality with elevated FGF-23 and LVH. Further research should
      ascertain if lowering levels of FGF-23 translates to improved clinical outcomes.

PMID- 21860795
TI  - Sex Differences in Medication and Primary Healthcare Use before and after Spousal
      Bereavement at Older Ages in Denmark: Nationwide Register Study of over 6000
      Bereavements.
AB  - Background. The study aimed to examine sex differences in healthcare use before
      and after widowhood to investigate whether reduced healthcare use among widowers
      compared with widows may partially explain excess mortality and more adverse
      health outcomes among men than women after spousal loss. Methods. All individuals
      alive and aged at least 60 years in 1996 and who became widowed in the period
      from 1996 to 2003 were selected from the 5% sample of the total Danish population
      and all Danish twins. The healthcare use was assessed as the average daily all
      cause and major system-specific medication use and the average annual number of
      visits to general physicians (GPs). Results. The average daily use of all-cause
      and major system-specific medications, as well as the number of GP visits
      increased over the period from 1 year before and up to 5 years after a spouse's
      death, but there were no sex-specific patterns in the trajectories of medication
      use and number of GP visits after conjugal loss. Conclusion. We found little
      support for the hypothesis that reduced healthcare use contributes to the
      explanation of more adverse health outcomes after conjugal loss in men compared
      with women in Denmark.

PMID- 21860796
TI  - First Steps towards Evidence-Based Preventive Home Visits: Experiences Gathered
      in a Swedish Municipality.
AB  - The purpose of preventive home visits is to promote overall health and wellbeing
      in old age. The aim of this paper was to describe the process of the development
      of evidence-based preventive home visits, targeting independent community-living
      older persons. The evidence base was generated from published studies and
      practical experiences. The results demonstrate that preventive home visits should
      be directed to persons 80 years old and older and involve various professional
      competences. The visits should be personalized, lead to concrete interventions,
      and be followed up. The health areas assessed should derive from a broad
      perspective and include social, psychological, and medical aspects. Core
      components in the protocol developed in this study captured physical, medical,
      psychosocial, and environmental aspects. Results of a pilot study showed that the
      protocol validly identified health risks among older people with different levels
      of ADL dependence.

PMID- 21860797
TI  - Mechanism(s) of Toxic Action of Zn and Selenite: A Study on AS-30D Hepatoma Cells
      and Isolated Mitochondria.
AB  - Mitochondria of AS-30D rat ascites hepatoma cells are found to be the main target
      for Zn(2+) and sodium selenite (Na(2)SeO(3)). High [mu]M concentrations of Zn(2+)
      or selenite were strongly cytotoxic, killing the AS-30D cells by both apoptotic
      and necrotic ways. Both Zn(2+) and selenite produced strong changes in
      intracellular generation of reactive oxygen species (ROS) and the mitochondrial
      dysfunction via the mitochondrial electron transport chain (mtETC) disturbance,
      the membrane potential dissipation, and the mitochondrial permeability transition
      pore opening. The significant distinctions in toxic action of Zn(2+) and selenite
      on AS-30D cells were found. Selenite induced a much higher intracellular ROS
      level (the early event) compared to Zn(2+) but a lower membrane potential loss
      and a lower decrease of the uncoupled respiration rate of the cells, whereas the
      mtETC disturbance was the early and critical event in the mechanism of Zn(2+)
      cytotoxicity. Sequences of events manifested in the mitochondrial dysfunction
      produced by the metal/metalloid under test are compared with those obtained
      earlier for Cd(2+), Hg(2+), and Cu(2+) on the same model system.

PMID- 21860798
TI  - Risk factors associated with false positive HIV test results in a low-risk urban
      obstetric population.
AB  - OBJECTIVE: To examine risk factors for false positive HIV enzyme immunoassay
      (EIA) testing at delivery. STUDY DESIGN: A review of pregnant women who delivered
      at Parkland Hospital between 2005 and 2008 was performed. Patients routinely
      received serum HIV EIA testing at delivery, with positive results confirmed
      through immunofluorescent testing. Demographics, HIV, hepatitis B surface antigen
      (HBsAg), and rapid plasma reagin (RPR) results were obtained. Statistical
      analyses included Pearson's chi-square and Student's t-test. RESULTS: Of 47,794
      patients, 47,391 (99%) tested negative, 145 (0.3%) falsely positive, 172 (0.4%)
      positive, and 86 (0.2%) equivocal or missing HIV results. The positive predictive
      value of EIA was 54.3%. Patients with false positive results were more likely
      nulliparous (43% versus 31%, P < 0.001) and younger (23.9 +/- 5.7 versus 26.2 +/-
      5.9 years, P < 0.001). HIV positive patients were older than false positive
      patients and more likely positive for HBsAg and RPR. CONCLUSION: False positive
      HIV testing at delivery using EIA is associated with young maternal age and
      nulliparity in this population.

PMID- 21860799
TI  - Clopidogrel-induced neutropenia after coronary stenting: is cilostazol a good
      alternative?
AB  - Dual antiplatelet therapy with aspirin plus thienopyridines has become the
      standard treatment of patients undergoing coronary stenting. Clopidogrel has
      mostly replaced the use of ticlopidine due to its more favourable adverse event
      profile. However, also the use of clopidogrel is not without side effects.
      Clopidogrel major adverse events are represented by marrow suppression,
      manifesting with aplastic anaemia, thrombocytopenia and neutropenia. When
      clopidogrel toxicity occurs, there are few and unsubstantiated alternative
      treatments and thus, in these cases, medical decisions may be very difficult. We
      report a case of clopidogrel-induced bone marrow toxicity manifesting with severe
      neutropenia in a patient treated with multiple coronary stents and provide
      suggestions for an alternative treatment.

PMID- 21860800
TI  - Management of patients with atrial fibrillation: specific considerations for the
      old age.
AB  - Atrial fibrillation (AF) is the commonest of all sustained arrhythmias, and most
      of the patients seeking medical therapy are in the elderly age group. The
      management of these patients is particularly difficult due to associated
      comorbidities. Hypertension, congestive heart failure, left ventricular
      hypertrophy, and coronary artery disease are often present in the elderly patient
      population, and therefore, antiarrhythmic drugs often fail due to side effects,
      proarrhythmia, or poor rhythm control. Recently, radiofrequency catheter ablation
      has been widely performed as an efficient therapy for recurrent, drug-refractory
      AF. Nevertheless, patients at old age were underrepresented in prior AF ablation
      trials, and the current guidelines for catheter ablation of AF recommend a
      noninvasive approach in the elderly patient group due to the lack of clinical
      data supporting ablation therapy. However, study results of our group and others
      are suggesting that catheter ablation is a safe and effective treatment for
      patients over the age of 65 years with symptomatic, drug-refractory AF, and
      therefore, patients should not be precluded from catheter ablation only on the
      basis of age. This paper discusses the pharmacological (rhythm control, rate
      control, and anticoagulation) and catheter management of AF in the elderly
      population.

PMID- 21860801
TI  - Extravascular lung water and acute lung injury.
AB  - Acute lung injury carries a high burden of morbidity and mortality and is
      characterised by nonhydrostatic pulmonary oedema. The aim of this paper is to
      highlight the role of accurate quantification of extravascular lung water in
      diagnosis, management, and prognosis in "acute lung injury" and "acute
      respiratory distress syndrome". Several studies have verified the accuracy of
      both the single and the double transpulmonary thermal indicator techniques. Both
      experimental and clinical studies were searched in PUBMED using the term
      "extravascular lung water" and "acute lung injury". Extravascular lung water
      measurement offers information not otherwise available by other methods such as
      chest radiography, arterial blood gas, and chest auscultation at the bedside.
      Recent data have highlighted the role of extravascular lung water in response to
      treatment to guide fluid therapy and ventilator strategies. The quantification of
      extravascular lung water may predict mortality and multiorgan dysfunction. The
      limitations of the dilution method are also discussed.

PMID- 21860803
TI  - Toward intelligent hemodynamic monitoring: a functional approach.
AB  - Technology is now available to allow a complete haemodynamic analysis; however
      this is only used in a small proportion of patients and seems to occur when the
      medical staff have the time and inclination. As a result of this, significant
      delays occur between an event, its diagnosis and therefore, any treatment
      required. We can speculate that we should be able to collect enough real time
      information to make a complete, real time, haemodynamic diagnosis in all
      critically ill patients. This article advocates for "intelligent haemodynamic
      monitoring". Following the steps of a functional analysis, we answered six basic
      questions. (1) What is the actual best theoretical model for describing
      haemodynamic disorders? (2) What are the needed and necessary input/output data
      for describing this model? (3) What are the specific quality criteria and
      tolerances for collecting each input variable? (4) Based on these criteria, what
      are the validated available technologies for monitoring each input variable,
      continuously, real time, and if possible non-invasively? (5) How can we integrate
      all the needed reliably monitored input variables into the same system for
      continuously describing the global haemodynamic model? (6) Is it possible to
      implement this global model into intelligent programs that are able to
      differentiate clinically relevant changes as opposed to artificial changes and to
      display intelligent messages and/or diagnoses?

PMID- 21860802
TI  - Physiologic and Clinical Principles behind Noninvasive Resuscitation Techniques
      and Cardiac Output Monitoring.
AB  - Clinical assessment and vital signs are poor predictors of the overall
      hemodynamic state. Optimal measurement of the response to fluid resuscitation and
      hemodynamics has previously required invasive measurement with radial and
      pulmonary artery catheterization. Newer noninvasive resuscitation technology
      offers the hope of more accurately and safely monitoring a broader range of
      critically ill patients while using fewer resources. Fluid responsiveness, the
      cardiac response to volume loading, represents a dynamic method of improving upon
      the assessment of preload when compared to static measures like central venous
      pressure. Multiple new hemodynamic monitors now exist that can noninvasively
      report cardiac output and oxygen delivery in a continuous manner. Proper
      assessment of the potential future role of these techniques in resuscitation
      requires understanding the underlying physiologic and clinical principles,
      reviewing the most recent literature examining their clinical validity, and
      evaluating their respective advantages and limitations.

PMID- 21860804
TI  - The association of chronic kidney disease and metabolic syndrome with incident
      cardiovascular events: multiethnic study of atherosclerosis.
AB  - Background. There is an association between chronic kidney disease (CKD) and
      metabolic syndrome (MetS). We examined the joint association of CKD and MetS with
      incident cardiovascular (CVD) events in the Multiethnic Study of Atherosclerosis
      (MESA) cohort. Methods. We analyzed 2,283 Caucasians, 363 Chinese, 1,449 African
      Americans, and 1,068 Hispanics in the MESA cohort. CKD was defined by cystatin C
      estimated glomerular filtration rate <= 60 mL/min/1.73 m(2) and MetS was defined
      by NCEP criteria. Cox proportional regression adjusting for age, ethnicity,
      gender, study site, education, income, smoking, alcohol use, physical activity,
      and total and LDL cholesterol was performed to assess the joint association of
      CKD and MetS with incident CVD events. Participants were divided into four groups
      by presence of CKD and/or MetS and compared to the group without CKD and MetS
      (CKD(-)/MetS(-)). Tests for additive and multiplicative interactions between CKD
      and MetS and prediction of incident CVD were performed. Results. During follow-up
      period of 5.5 years, 283 participants developed CVD. Multivariate Cox regression
      analysis demonstrated that CKD and MetS were independent predictors of CVD
      (hazard ratio, 2.02 for CKD, and 2.55 for MetS). When participants were compared
      to the CKD(-)/MetS(-) group, adjusted HR for the CKD(+)/MetS(+) group was 5.56
      (95% CI 3.72-8.12). There was no multiplicative interaction between CKD and MetS
      (P = 0.2); however, there was presence of additive interaction. The relative
      excess risk for additive interaction (RERI) was 2.73, P = 0.2, and the
      attributable portion (AP) was 0.49 (0.24-0.74). Conclusion. Our findings
      illustrate that the combination of CKD and MetS is a strong predictor of incident
      clinical cardiovascular events due to presence of additive interaction between
      CKD and MetS.

PMID- 21860806
TI  - Preoperative thyrotropin serum concentrations gradually increase from benign
      thyroid nodules to papillary thyroid microcarcinomas then to papillary thyroid
      cancers of larger size.
AB  - We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients
      operated on for nodular thyroid disease (NTD). TSH levels for cases with final
      benign disease and differentiated thyroid carcinoma (DTC) were compared. No
      evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was
      present in 76 cases (19.7%). Mean TSH concentration was 1.36 +/- 1.62 mU/L in
      benign patients and 2.08 +/- 2.1 in cases with malignant lesions (P = 0.0013).
      The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC)
      versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 +/- 1.52 in PTMC
      and 2.42 +/- 2.5 in TCLS. Significant differences were found when all groups
      (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons
      between them showed that differences were only significant between benign and
      TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a
      final diagnosis of DTC. Moreover, it appears that there exists an increment in
      tumor size as a function of increment in the TSH level.

PMID- 21860805
TI  - Oxidative Stress and Inflammation in Heart Disease: Do Antioxidants Have a Role
      in Treatment and/or Prevention?
AB  - Inflammation triggered by oxidative stress is the cause of much, perhaps even
      most, chronic human disease including human aging. The oxidative stress
      originates mainly in mitochondria from reactive oxygen and reactive nitrogen
      species (ROS/RNS) and can be identified in most of the key steps in the
      pathophysiology of atherosclerosis and the consequential clinical manifestations
      of cardiovascular disease. In addition to the formation of atherosclerosis, it
      involves lipid metabolism, plaque rupture, thrombosis, myocardial injury,
      apoptosis, fibrosis and failure. The recognition of the critical importance of
      oxidative stress has led to the enthusiastic use of antioxidants in the treatment
      and prevention of heart disease, but the results of prospective, randomized
      clinical trials have been overall disappointing. Can this contradiction be
      explained and what are its implications for the discovery/development of future
      antioxidant therapeutics?

PMID- 21860807
TI  - Prognosis of patients with papillary thyroid carcinoma located in one lobe
      showing lateral node metastasis in the contralateral but not ipsilateral
      compartment.
AB  - Papillary thyroid carcinoma (PTC) frequently metastasizes to the lymph node in
      lateral compartment, which can often be detected on preoperative ultrasonography
      (N1b). However, PTC located in one lobe showing contralateral but not ipsilateral
      N1b is not common. We analyzed the clinicopathological features and prognosis of
      13 patients with PTC limited in one lobe showing contralateral but not
      ipsilateral N1b. Sizes of the primary lesions ranged from 0.8 cm to 3.0 cm and
      only 2 tumors showed extrathyroid extension. Metastatic lateral node measured
      from 0.6 to 3.1 cm. Ten patients showed pathological central node metastasis and
      5 had minute PTC lesions in the contralateral lobe. However, 3 patients did not
      show either of these. None of the patients have developed carcinoma recurrence or
      died of carcinoma to date. Taken together, PTC located in one lobe with
      contralateral but not ipsilateral N1b is rare and generally shows an indolent
      behavior. Although most patients had central node metastasis and/or minute PTC
      lesions in the contralateral lobe, it is also possible for carcinoma cells to
      metastasize directly from primary lesions to the contralateral lateral node.
      Total thyroidectomy with central node dissection and therapeutic MND of the
      contralateral compartment may be an acceptable surgical design and bilateral MND
      might not be mandatory.

PMID- 21860809
TI  - Exercise preferences are different after stroke.
AB  - Objective. To explore exercise preferences in stroke survivors and controls.
      Methods. A novel scale-the Exercise Preference Questionnaire-was developed for
      this study. This questionnaire, together with established assessments of physical
      activities, mood, and quality of life, was completed in a single assessment
      session. Results. Twenty-three adult stroke survivors (mean age 63, 65% male) and
      41 healthy controls (mean age 61, 66% male) participated. The groups differed on
      4 of the 5 a priori exercise preference factors: relative to controls, stroke
      survivors preferred exercise to be more structured, in a group, at a gym or
      fitness centre, and for exercises to be demonstrated. Factor analysis yielded 6
      data-driven factors, and these factors also differentiated stroke and control
      groups. There was evidence that group differences were diminished when activity
      levels and psychological wellbeing were accounted for. Individual variability in
      exercise preferences and reported barriers to exercise are outlined. Conclusion.
      Stroke survivors have different exercise preferences, and a better understanding
      of these preferences can be used to inform rehabilitation programs and increase
      adherence.

PMID- 21860808
TI  - Fatigue after Stroke: The Patient's Perspective.
AB  - Background. Fatigue after stroke is common and distressing to patients. Aims. Our
      aims were to explore patients' perceptions of post-stroke fatigue, including the
      causes of fatigue and the factors that alleviate fatigue, in a mixed methods
      study. Results. We interviewed 15 patients who had had a stroke and were
      inpatients on stroke rehabilitation wards. A substantial proportion of patients
      reported that their fatigue started at the time of their stroke. Various
      different factors were reported to improve fatigue, including exercise, good
      sleep, rehabilitation and rest. Fatigue influences patients' sense of "control"
      after their stroke. Conclusion. Our results are consistent with the possibility
      that poststroke fatigue might be triggered by factors that occur at the time of
      the stroke (e.g., the stroke lesion itself, or admission to hospital) and then
      exacerbated by poor sleep and boredom. These factors should be considered when
      developing complex interventions to improve post-stroke fatigue.

PMID- 21860810
TI  - Safety of early carotid artery stenting after systemic thrombolysis: a single
      center experience.
AB  - Background. Patients with acute ischemic stroke due to internal carotid artery
      (ICA) disease are at high risk of early stroke recurrence. A combination of IV
      thrombolysis and early carotid artery stenting (CAS) may result in more effective
      secondary stroke prevention. Objective. We tested safety and durability of early
      CAS following IV thrombolysis in stroke patients with residual stenosis in the
      symptomatic ICA. Methods. Of consecutive patients treated with IV rtPA, those
      with residual ICA stenosis >=70% or <70% with an ulcerated plaque underwent early
      CAS (>24 hours). The protocol included pre-rtPA MRI and MR angiography, and post
      rtPA carotid ultrasound and CT angiography. Stroke severity was assessed by the
      NIH Stroke Scale (NIHSS). Three- and twelve-month stent patency was assessed by
      ultrasound. Twelve-month functional outcome was assessed by the modified Rankin
      Scale (mRS). Results. Of 145 consecutive IV rtPA-treated patients, 6 (4%)
      underwent early CAS. Median age was 76 (range 67-78) years, median NIHSS at
      stroke onset was 12 (range 9-16) and 7 (range 7-8) before CAS. Median onset-to
      CAS time was 48 (range 30-94) hours. A single self-expandable stent was implanted
      to cover the entire lesion in all patients. The procedure was uneventful in all
      patients. After 12 months, all patients had stent patency, and the functional
      outcome was favourable (mRS <= 2) in all but 1 patient experiencing a recurrent
      stroke for new-onset atrial fibrillation. Conclusion. This small case series of a
      single centre suggests that early CAS may be considered a safe alternative to CEA
      after IV rtPA administration in selected patients at high risk of stroke
      recurrence.

PMID- 21860811
TI  - Long-Term Survival of Mycobacterium avium subsp. paratuberculosis in Fecal
      Samples Obtained from Naturally Infected Cows and Stored at -18 degrees C and -70
      degrees C.
AB  - The objective was to evaluate the survival of Mycobacterium paratuberculosis
      (Map) in naturally infected dairy cows feces under long periods of freezing at 
      18 degrees C and -70 degrees C. Samples were collected from cows previously
      tested positive with serum ELISA or fecal culture, or with clinical signs of
      Johne's disease. Samples were stored at -18 degrees C and/or -70 degrees C and
      recultured in Herrold's egg yolk media every 3-6 months. A proportional odds
      mixed model was used for data analysis. Sixty nine fecal samples were stored for
      different periods between September 2002 and January 2005. Of these, 45 (65%)
      were stored at -18 degrees C and 24 (35%) at -70 degrees C. Average number of
      days between repeated culture dates was 98 and 84 for -18 degrees C and -70
      degrees C, respectively. Median number of repeated cultures was 6 and 4 for
      samples stored at -18 degrees C and -70 degrees C, respectively. After adjusting
      for initial sample bacterial load, the effects of temperature or number of
      thawing and refreezing cycles on Map viability were not significant. The
      probability that a sample decreases from high to moderate-low bacterial load and
      from moderate-low to negative bacterial load was 13.5% per month. Although this
      study found gradual reduction of Map concentration in stored fecal samples
      through time, overall survival in -18 degrees C can ease fecal samples management
      in laboratories with low-processing capacity or lack of -70 degrees C freezer.

PMID- 21860812
TI  - Helicobacter pylori Has an Inverse Relationship With Severity of Reflux
      Esophagitis.

PMID- 21860813
TI  - Rome III Criteria for Functional Gastrointestinal Disorders: Is There a Need for
      a Better Definition?

PMID- 21860816
TI  - Health related quality of life in functional gastrointestinal disorders in Asia.
AB  - The importance of health-related quality of life (HRQOL) continues to grow, as
      clinicians and clinical researchers have recognized the impact of the functional
      gastrointestinal disorders. Limited information is available on the performance
      of HRQOL questionnaires in Asia. Furthermore, the effect across different
      cultural settings of functional gastrointestinal disorders on HRQOL has been
      little studied in Eastern countries. We summarized recent studies on HRQOL in
      Korean patients with functional gastrointestinal disorders as well as other Asian
      literatures. Functional gastrointestinal disorders-related symptoms had a great
      effect on the HRQOL of Korean patients. These results and their considerable
      prevalence in Korea indicate that functional gastrointestinal disorders have a
      substantial social impact in this country.

PMID- 21860815
TI  - Epidemiology of uninvestigated and functional dyspepsia in Asia: facts and
      fiction.
AB  - Dyspepsia is a syndrome consisting of epigastric pain, burning, fullness,
      discomfort, early satiety, nausea, vomiting and belching. Functional dyspepsia
      (FD) is diagnosed if upper gastrointestinal endoscopy does not show structural
      abnormality explaining these symptoms. 8%-30% and 8%-23% of Asian people suffer
      from of uninvestigated dyspepsia and FD, respectively. Most patients with
      uninvestigated dyspepsia are found to have FD. Patients with FD are usually young
      and there is no predilection to any gender. Overlap of FD with other functional
      bowel diseases such as irritable bowel syndrome and gastroesophageal reflux
      disease is common in Asia. Cultural difference in reporting of symptoms of
      dyspepsia is well-known. Moreover, dietary factors, socio-cultural and
      psychological issues, gastrointestinal infection including that caused by
      Helicobacter pylori, frequency of organic diseases such as peptic ulcer and
      gastric cancer responsible for dyspeptic symptoms in the study population may
      also influence epidemiology of dyspepsia. There is considerable heterogeneity in
      the above issues among different Asian countries. More studies on epidemiology of
      FD are needed in Asia.

PMID- 21860817
TI  - Irritable bowel syndrome, gut microbiota and probiotics.
AB  - Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal
      symptoms including chronic abdominal pain or discomfort and altered bowel habits.
      The etiology of IBS is multifactorial, as abnormal gut motility, visceral
      hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal
      autonomic nervous system are all implicated in disease progression. Based on
      recent experimental and clinical studies, it has been suggested that additional
      etiological factors including low-grade inflammation, altered gut microbiota and
      alteration in the gut immune system play important roles in the pathogenesis of
      IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be
      an ideal treatment for IBS. Probiotics are live organisms that are believed to
      cause no harm and result in health benefits for the host. Clinical efficacy of
      probiotics has been shown in the treatment or prevention of some gastrointestinal
      inflammation-associated disorders including traveler's diarrhea, antibiotics
      associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing
      enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected
      by altered gut microbiota and gut inflammation-immunity are reviewed. The effect
      of probiotics on the gut inflammation-immune systems and the results from
      clinical trials of probiotics for the treatment of IBS are also summarized.

PMID- 21860819
TI  - Gastroesophageal Reflux Disease in Type II Diabetes Mellitus With or Without
      Peripheral Neuropathy.
AB  - BACKGROUND/AIMS: Patients with type II diabetes mellitus (DM) were known to have
      higher prevalence of gastroesophageal reflux disease (GERD). Recent studies have
      shown that neuropathy has positive role on the development of GERD in type II DM,
      although its pathogenesis has not been fully understood yet. The aim of this
      study was to investigate whether neuropathy really contribute to the development
      of GERD and typical GERD symptoms in patients with type II DM in Korea. METHODS:
      One hundred and nineteen patients with type II DM who had given informed consents
      were enrolled. All patients underwent electromyography to check the presence of
      peripheral neuropathy, face-to-face interview to evaluate their typical GERD
      symptoms and esophagogastroduodenoscopy to look for the presence of erosive
      esophagitis. Ninety-five patients were finally included for this study and they
      were divided according to the presence or absence of the peripheral neuropathy.
      RESULTS: The mean age of 95 patients was 59.3 +/- 9.1 years and the mean disease
      duration of DM was 9.3 +/- 5.9 years. Typical GERD symptoms were similarly found
      in both groups with and without peripheral neuropathy (23.6% vs 22.8%, P =
      0.921). Erosive esophagitis was more prevalent in patients with neuropathy than
      in those without neuropathy (31.5% vs 10.5%, P = 0.022). CONCLUSIONS: In patients
      with type II DM, peripheral neuropathy is an independent risk factor for the
      erosive esophagitis. However, peripheral neuropathy did not contribute to the
      presence of the typical GERD symptoms.

PMID- 21860818
TI  - Helicobacter pylori Serology Inversely Correlated With the Risk and Severity of
      Reflux Esophagitis in Helicobacter pylori Endemic Area: A Matched Case-Control
      Study of 5,616 Health Check-Up Koreans.
AB  - BACKGROUND/AIMS: The role of Helicobacter pylori in gastroesophageal reflux
      disease remains still controversial and the effect of the organism on severity of
      reflux esophagitis have been rarely issued. The aim of this study was to
      investigate the relationship between H. pylori infection and reflux esophagitis,
      and especially the severity of reflux esophagitis. METHODS: We performed a cross
      sectional case-control study of 5,616 subjects undergoing both upper endoscopy
      and H. pylori serology during health Check-up (2,808 cases vs age- and sex
      matched controls). Smoking, alcohol, body mass index and waist circum - ference
      were added to a multiple regression model. RESULTS: Prevalence of H. pylori
      infection was lower in cases with reflux esophagitis than in controls (38.4% vs
      58.2%, P < 0.001) and negative associations with H. pylori infection continued
      across the grade of esophagitis (46.7% in Los Angeles classification M [LA-M],
      34.3% in LA-A or LA-B and 22.4% in LA-C or LA-D, P < 0.001). Positive serology
      for H. pylori independently reduced the risk of reflux esophagitis (adjusted OR,
      0.44; 95% CI, 0.39-0.49). Notably, the negative associations continued across the
      grade of esophagitis with adjusted ORs of 0.63 in LA-M, 0.36 in LA-A or LA-B and
      0.20 in LA-C or LA-D (P < 0.001). CONCLUSIONS: In a age-sex matched Korean, H.
      pylori seropositivity was independently and inversely associated with the risk
      and severity of reflux esophagitis, suggesting the organism may have a protective
      role against gastroesophageal reflux disease.

PMID- 21860820
TI  - Functional Gastrointestinal Disorders Diagnosed by Rome III Questionnaire in
      Korea.
AB  - BACKGROUND/AIMS: Rome criteria classifying functional gastrointestinal disorder
      (FGID) were updated. The aims of this study were to assess the spectra of FGID
      and to evaluate the applicability of Rome III criteria in Korea. METHODS: New
      patients who visited 2 primary clinics and 2 tertiary care hospitals were
      consecutively invited to complete questionnaires. These consisted of
      questionnaires for FGID based on Rome III criteria and symptom checklist-90
      revised for somatization, depression and anxiety. RESULTS: A total of 786
      patients was participated. Among them, FGID was observed in 49.7%. In the
      patients with FGID, functional dyspepsia was most common (46.0%) followed by
      irritable bowel syndrome (IBS, 40.2%). Functional dyspepsia was most common both
      in the primary care clinics and tertiary care hospitals. Postprandial distress
      syndrome was the most common subtype and the frequency of epigastric pain
      syndrome was low. There were few responders for constipation as Bristol types 1
      and 2 and for diarrhea as types 6 and 7 in subtype classification using the
      Bristol Stool Form Scale. Thereby, unspecified IBS defined by stool form was
      unexpectedly common in 43.9% of IBS, whereas unspedified IBS defined by Rome III
      definition was 5.1%. Patients with overlap FGIDs had higher score of anxiety,
      depression or somatization. CONCLUSIONS: FGIDs were common both in primary care
      clinics and tertiary care hospitals of Korea. Overlap FGIDs is still common by
      Rome III criteria, which may limits its wide application.

PMID- 21860814
TI  - Stress-related alterations of visceral sensation: animal models for irritable
      bowel syndrome study.
AB  - Stressors of different psychological, physical or immune origin play a critical
      role in the pathophysiology of irritable bowel syndrome participating in symptoms
      onset, clinical presentation as well as treatment outcome. Experimental stress
      models applying a variety of acute and chronic exteroceptive or interoceptive
      stressors have been developed to target different periods throughout the lifespan
      of animals to assess the vulnerability, the trigger and perpetuating factors
      determining stress influence on visceral sensitivity and interactions within the
      brain-gut axis. Recent evidence points towards adequate construct and face
      validity of experimental models developed with respect to animals' age, sex,
      strain differences and specific methodological aspects such as non-invasive
      monitoring of visceromotor response to colorectal distension as being essential
      in successful identification and evaluation of novel therapeutic targets aimed at
      reducing stress-related alterations in visceral sensitivity. Underlying
      mechanisms of stress-induced modulation of visceral pain involve a combination of
      peripheral, spinal and supraspinal sensitization based on the nature of the
      stressors and dysregulation of descending pathways that modulate nociceptive
      transmission or stress-related analgesic response.

PMID- 21860821
TI  - Effects of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors on the
      Rate of Gastric Emptying: A Crossover Study Using a Continuous Real-Time C Breath
      Test (BreathID System).
AB  - BACKGROUND/AIMS: The effects of Histamine-2 receptor antagonists and proton pump
      inhibitors on the gastrointestinal motility have not yet been sufficiently
      investigated. The aim of this study was to determine the effects of intravenous
      bolus administration of famotidine and omeprazole on the rate of gastric emptying
      using the continuous (13)C breath test (BreathID system, Exalenz Bioscience Ltd,
      Israel). METHODS: Twelve healthy male volunteers participated in this randomized,
      3-way crossover study. After fasting overnight, the subjects were randomly
      assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline
      alone by intravenous bolus injection before a test meal (200 kcal per 200 mL,
      containing 100 mg of (13)C-acetate). Gastric emptying was monitored for 4 hours
      after the ingestion of test meal by the (13)C-acetic acid breath test performed
      using the BreathID system. RESULTS: No significant differences in the calculated
      parameters, namely, the T(1/2), T(lag), GEC, beta and kappa, were observed among
      the 3 test conditions. CONCLUSIONS: The study revealed that intravenous
      administration of gastric acid suppressant drugs had no significant influence on
      the rate of gastric emptying in comparison with that of saline alone as a
      placebo. Our results indicating the absence of any effect of either famotidine or
      omeprazole on accelerating the rate of gastric emptying suggest that both
      medications can be administered safely to patients suffering from hemorrhagic
      peptic ulcers who need to be kept nil by mouth from the viewpoint of possible
      acceleration of gastrointestinal motility in the clinical setting.

PMID- 21860822
TI  - Are Food Constituents Relevant to the Irritable Bowel Syndrome in Young Adults? -
      A Rome III Based Prevalence Study of the Korean Medical Students.
AB  - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is prevalent in general
      population. This study investigates the prevalence of IBS in medical college
      students in Korea as well as the influence of dietary habits and nutritional
      intake on IBS. METHODS: This study is a cross-sectional study of 319 students
      (239 males and 80 females, age 22.3 +/- 2.5 years) from the 6 grade levels of the
      Medical College in Korea. All students filled out a self-reported questionnaire
      for ROME III criteria. They also completed a questionnaire to validate dietary
      habits and food frequency in Korean. RESULTS: The overall prevalence of IBS was
      29.2% without correlation to age, body mass index and grade level in Medical
      School. However, the prevalence was significantly higher in females than males
      (33/80 vs 60/239, P = 0.007). There were no significant differences between the
      IBS-group and the non-IBS group in aspect of nutrition. Not only the diet habits,
      but also the daily nutritional intake, and even the breakdown into the 12
      micronutrients, yielded no significant differences between the 2 groups.
      CONCLUSIONS: Twenty-nine percent of the medical college students have IBS with a
      greater prevalence in females. The dietary habits and nutritional intake of the
      students might not be associated with IBS.

PMID- 21860823
TI  - Determinant of anal resting pressure gradient in association with continence
      function.
AB  - BACKGROUND/AIMS: Gradient of resting pressure across the anal canal, which is
      known to have a role in continence mechanism, has 2 components of determination;
      pressure and length factor of the anal canal. This study evaluates which factor
      between them plays more significant role for the determination of the gradient in
      association with continence function. METHODS: Anal manometric measurements of 69
      patients with fecal incontinence and 60 controls were retrospectively reviewed.
      In addition to resting pressure gradient, typical manometric parameters such as
      maximum resting pressure, basal resting pressure, length of the anal canal,
      length of high pressure zone and relative position of highest pressure, which
      were measured with rapid pull-through technique were all contrasted. RESULTS:
      Demographics of the 2 groups were similar. Maximum resting pressures of patients
      with incontinence and controls were 59.1 +/- 28.3, 74.6 +/- 24.0 mmHg (P =
      0.001), respectively. Basal resting pressures were 5.7 +/- 6.4 and 7.3 +/- 3.9
      mmHg (P = 0.097), lengths of the anal canal were 35.8 +/- 9.1 and 38.1 +/- 8.3 mm
      (P = 0.133), lengths of high pressure zone were 21.2 +/- 6.7 and 23.3 +/- 6.5 mm
      (P = 0.091), relative positions of highest pressure were 69.2 +/- 10.6 and 70.1%
      +/- 14.9% (P = 0.717) and resting pressure gradients were 2.28 +/- 1.08 and 2.74
      +/- 1.14 mmHg/mm (P = 0.019), respectively. Difference was significant in maximum
      resting pressure and resting pressure gradient, but not in length factors such as
      full length of the anal canal, length of high pressure zone and relative position
      of highest pressure. CONCLUSIONS: Proximal location of high pressure zone in
      incontinent patients is not definite and resting pressure gradient of the anal
      canal depends more on pressure factor than length factor in association with
      continence function.

PMID- 21860824
TI  - Psychiatric Co-morbidity and Efficacy of Mirtazapine Treatment in Young Subjects
      With Chronic or Cyclic Vomiting Syndromes: A Case Series.
AB  - The aim of this case report was to evaluate the psychiatric co-morbidity and
      efficacy of mirtazapine treatment in young subjects with chronic or cyclic
      vomiting syndromes. This is a case series of 8 young subjects (age range of 6-16
      years, 11.12 +/- 3.52 years) who were referred or consulted to child psychiatry
      department. They were referred or consulted by pediatric gastroenterology or
      surgery departments for the presence of non-remitting and medically unexplained
      vomiting. They were investigated for co-morbid psychiatric disorders using a
      structured psychiatric interview. An open trial of mirtazapine was conducted for
      the treatment and/or prevention of vomiting. Primary outcome measure was Clinical
      Global Impression-Improvement scale. Subjects were diagnosed with chronic (n = 5)
      or cyclic (n = 3) vomiting syndromes. Duration of vomiting ranged from 6 months
      to 10 years (3.5 +/- 3.2 years). All subjects received multiple psychiatric
      diagnoses with anxiety disorders being the most frequent. Maximum mirtazapine
      dosage was 7.5-30 mg/day (16.00 +/- 6.16 mg/day). Three subjects showed complete
      remission and 5 subjects showed much to very much improvement in vomiting. Most
      frequent side effects were increased appetite, weight gain and sedation. Young
      subjects with chronic or cyclic vomiting may frequently suffer anxiety and/or
      depressive symptoms or disorders. Mirtazapine could be an effective treatment
      option for the treatment of vomiting and co-morbid anxiety or depressive
      disorders in these subjects. More systematic research are needed on this topic.

PMID- 21860825
TI  - How to interpret hydrogen breath tests.
AB  - Hydrogen breath tests using various substrates like glucose, lactulose, lactose
      and fructose are being used more and more to diagnose small intestinal bacterial
      overgrowth (SIBO) and lactose or fructose malabsorption. Though quantitative
      culture of jejunal aspirate is considered as gold standard for the diagnosis of
      SIBO, hydrogen breath tests, in spite of their low sensitivity, are popular for
      their non-invasiveness. Glucose hydrogen breath test is more acceptable for the
      diagnosis of SIBO as conventionally accepted double-peak criterion on lactulose
      hydrogen breath test is very insensitive and recently described early-peak
      criterion is often false positive. Hydrogen breath test is useful to diagnose
      various types of sugar malabsorption. Technique and interpretation of different
      hydrogen breath tests are outlined in this review.

PMID- 21860826
TI  - Is a patient with asymptomatic esophagitis really hyposensitive to Acid and
      distention?

PMID- 21860827
TI  - Hypotonic upper esophageal sphincter with functional esophagogastric junction
      obstruction in a patient with oropharyngeal and esophageal Dysphagia.

PMID- 21860828
TI  - Novel technique for inducing neural crest fate in embryonic stem cells (stem
      cells 2009;27:2896-2905).

PMID- 21860829
TI  - Pneumatic Dilation versus Laparoscopic Heller's Myotomy for Idiopathic Achalasia
      (N Engl J Med 2011;364:1807-1816).

PMID- 21860830
TI  - How Useful the Combined Impedance-pH Monitoring Is for Evaluation of Refractory
      Reflux Symptoms?

PMID- 21860831
TI  - How Useful the Combined Impedance-pH Monitoring Is for Evaluation of Refractory
      Reflux Symptoms?: Author's Reply.

PMID- 21860832
TI  - Is alacrima so prevalent in patients with early-onset achalasia?

PMID- 21860833
TI  - Is Alacrima So Prevalent in Patients With Early-Onset Achalasia?: Author's reply.

PMID- 21860835
TI  - Non-erosive and uncomplicated erosive reflux diseases: Difference in
      physiopathological and symptom pattern.
AB  - AIM: To investigate differences in the physiopathological findings (manometry and
      pH monitoring) and symptoms between cases of non-erosive reflux disease (NERD)
      and erosive reflux disease (ERD) found positive at 24 h pH monitoring. METHODS:
      For a total of 670 patients who underwent 24 h pH monitoring, esophageal
      manometry and upper endoscopy were retrospectively evaluated, assessing the
      reflux symptoms, manometric characteristics of the lower esophageal sphincter
      (LES) and esophageal body and the presence or absence of esophagitis and hiatal
      hernia. Typical and atypical symptoms were also evaluated. For inclusion in the
      study, patients had to have NERD or ERD and be found positive on pH monitoring
      (NERD+). Patients with Gastroesophageal reflux disease (GERD) complicated by
      stenosis, ulcers or Barrett's esophagus were ruled out. RESULTS: 214 patients
      were involved in the study, i.e. 107 cases of NERD+ and 107 of ERD. There were no
      significant gender- or age-related differences between the two groups. The ERD
      group had more cases of hiatal hernia (P = 0.02) and more acid reflux, both in
      terms of number of reflux episodes (P = 0.01) and as a percentage of the total
      time with a pH < 4 (P = 0.00), when upright (P = 0.007) and supine (P = 0.00).
      The NERD+ cases had more reflux episodes while upright (P = 0.02) and the ERD
      cases while supine (P = 0.01). The LES pressure was higher in cases of NERD+ (P =
      0.03) while the amplitude and duration of their esophageal peristaltic waves
      tended to be better than in the ERD group (P >0.05). The NERD+ patients presented
      more often with atypical symptoms (P = 0.01). CONCLUSION: The NERD+ patients'
      fewer reflux episodes and the fact that they occurred mainly while in the upright
      position (unlike the cases of ERD) may be two factors that do not favor the onset
      of esophagitis. The frequently atypical symptoms seen in patients with NERD+ need
      to be accurately evaluated for therapeutic purposes because patients with GERD
      and atypical symptoms generally respond only partially to medical and surgical
      treatments.

PMID- 21860834
TI  - Mechanisms of Helicobacter pylori antibiotic resistance: An updated appraisal.
AB  - Helicobacter pylori (H. pylori) antibiotic resistance is the main factor
      affecting the efficacy of the current eradicating therapies. The aim of this
      editorial is to report on the recent information about the mechanisms accounting
      for the resistance to the different antibiotics currently utilized in H. pylori
      eradicating treatments. Different mechanisms of resistance to clarithromycin,
      metronidazole, quinolones, amoxicillin and tetracycline are accurately detailed
      (point mutations, redox intracellular potential, pump efflux systems, membrane
      permeability) on the basis of the most recent data available from the literature.
      The next hope for the future is that by improving the knowledge of resistance
      mechanisms, the elaboration of rational and efficacious associations for the
      treatment of the infection will be possible. Another auspicious progress might be
      the possibility of a cheap, feasible and reliable laboratory test to predict the
      outcome of a therapeutic scheme.

PMID- 21860836
TI  - Resolution of metabolic syndrome after following a gluten free diet in an adult
      woman diagnosed with celiac disease.
AB  - Adult celiac disease (CD) presents with very diverse symptoms that are clearly
      different from those typically seen in pediatric patients, including ferropenic
      anemia, dyspepsia, endocrine alterations and elevated transaminase concentration.
      We present the case of a 51-year-old overweight woman with altered basal blood
      glucose, hypercholesterolemia, hypertriglyceridemia and persisting elevated
      transaminase levels, who showed all the symptoms for a diagnosis of metabolic
      syndrome. Because she presented iron deficiency anemia, she was referred to the
      gastroenterology department and subsequently diagnosed with celiac disease after
      duodenal biopsies and detection of a compatible HLA haplotype. Gluten-free diet
      (GFD) was prescribed and after 6 mo the patient showed resolution of laboratory
      abnormalities (including recovering anemia and iron reserves, normalization of
      altered lipid and liver function parameters and decrease of glucose blood
      levels). No changes in weight or waist circumference were observed and no
      significant changes in diet were documented apart from the GFD. The present case
      study is the first reported description of an association between CD and
      metabolic syndrome, and invites investigation of the metabolic changes induced by
      gluten in celiac patients.

PMID- 21860838
TI  - Parimal Chowdhury's work on smoking related pancreatic disorders.
AB  - Cigarette smoking is a known risk factor for the development of numerous
      diseases. The role of nicotine in the induction of pancreatic inflammation and
      pancreatic cancer as a result of cigarette smoking has been recognized and
      reported in the literature. The mechanism by which nicotine induces such
      pathologies is as yet unknown. An understanding of the proliferative potential of
      nicotine in primary and tumor cells of the pancreas will allow us to develop
      measures that will ultimately lead to intervention, prevention and treatment of
      these diseases. Studies show that nicotine can increase the cell numbers of cer
      tain cancer cell lines, suggesting that exposure to nicotine can lead to the
      disruption of the dynamic balance between cell death and proliferation, which is
      required for normal functioning of cells. We hypothesize that nicotine induces
      oxidative stress in pancreatic acinar cells and thus contributes to this
      disruption. We have used the AR42J cell line in our study because of its
      stability as an immortal tumor cell line and its known physiological similarity
      to primary acinar cells. Our studies show that mitogen activated protein kinase
      signaling is induced by nicotine in AR42J cells, causing an increase in lipid
      peroxidation and a subsequent decrease in cell function. Our data suggest that
      exposure to nicotine induces oxidative stress, leading to cell injury and
      compromised function, thus implicating cigarette smoking as a plausible
      mechanism.

PMID- 21860837
TI  - Littoral cell angiomas of the spleen associated with solid pseudopapillary tumor
      of the pancreas.
AB  - Littoral cell angiomas (LCA) of the spleen are vascular tumors of unknown
      etiology arising from the littoral cells of the splenic red pulp sinuses. Usually
      a benign and incidental finding, LCA have been repeatedly reported in association
      with a variety of visceral malignancies and hold the potential for dissemination
      per se. We encountered a case of a 30 year old female who was diagnosed with
      solid pseudopapillary tumor of the head and distal pancreas by fine needle
      aspiration cytology. A distal pancreatectomy with splenectomy was performed in
      addition to a pylorus-preserving Whipple's procedure and cholecystectomy.
      Histopathological examination confirmed solid pseudopapillary tumor of the
      pancreas and showed multiple well-circumscribed anastomosing vascular channels in
      the spleen. The diagnosis of LCA of the spleen was confirmed by
      immunohistochemistry that revealed co-expression of endothelial cell marker, CD31
      and CD34, along with histiocytic marker, CD68 by the vascular lining cells. LCA
      has been previously reported in association with colorectal and pancreatic
      adenocarcinoma, malignant lymphoma, myelodysplasia and autoimmune disorders. We
      report the first case of LCA associated with solid pseudopapillary tumor of the
      pancreas.

PMID- 21860839
TI  - Janice Drew's work on diet and cancer.
AB  - Obesity and associated reduced consumption of plant derived foods are linked to
      increased risk of colon cancer as well as a number of other organ specific
      cancers. Inflammatory processes are a contributing factor but the precise
      mechanisms remain elusive. Obesity and cancer incidence are increasing worldwide,
      presenting bleak prospects for reducing, or preventing, obesity related cancers.
      The incidence of these preventable cancers can be achieved with greater
      understanding of the molecular mechanisms linking diet and carcinogenesis. Janice
      Drew has developed a research program over recent years to investigate molecular
      mechanisms related to consumption of anti-inflammatory metabolites generated from
      consumption of plant based diets, the impact of high fat diets and associated
      altered metabolism and obesity on regulation of colon inflammatory responses and
      processes regulating the colon epithelium. Comprehensive strategies have been
      developed incorporating transcriptomics, including the novel gene expression
      technology, the GenomeLab System and proteomics, together with biochemical
      analyses of plasma and tissue samples to assess correlated changes in oxidative
      stress, inflammation and pathology. The approaches developed have achieved
      success in establishing antioxidant and anti-inflammatory activity of dietary
      antioxidants and associated genes and pathways that interact to modulate redox
      status in the colon. Cellular processes and genes altered in response to obesity
      and high fat diets have provided evidence of molecular mechanisms that are
      implicated in obesity related cancer.

PMID- 21860840
TI  - Stress ulcer prophylaxis guidelines: Are they being implemented in Lebanese
      health care centers?
AB  - AIM: To evaluate the current practice of stress ulcer prophylaxis (SUP) in
      Lebanese Health care centers. METHODS: A multi-center prospective chart review
      study was conducted over 8 mo. A questionnaire was distributed to pharmacy
      students who collected data on demographics, SUP medications, dose, route,
      duration and associated risk factors. The appropriateness of SUP use was
      determined as per American Society of Health-System Pharmacists guidelines.
      Institutional review board approval was obtained from each hospital center.
      RESULTS: A total of 1004 patients were included. 67% of the patients who received
      prophylaxis did not have an indication for SUP. The majority (71.6%) of the
      patients who were administered parenteral drugs can tolerate oral medications.
      Overall, the regimen of acid-suppressant drugs was suboptimal in 87.6% of the
      sample. This misuse was mainly observed in non-teaching hospitals. CONCLUSION:
      This study highlighted the need, in Lebanese hospitals, to establish clinical
      practice guidelines for the use of SUP; mainly in non-critical care settings.

PMID- 21860841
TI  - Allergic rhinitis: relationships with anxiety and mood syndromes.
AB  - In this article, the authors examine the preponderance of publications pertaining
      to relationships between allergies and anxiety and mood syndromes. Through a
      review of the relevant articles in the PubMed and PsycINFO databases, the authors
      found that the majority of studies (9 of 11 studies on anxiety syndromes, 10 of
      12 studies on depressive syndromes) indicate associations between allergies and
      anxiety/mood syndromes, despite a number of methodological variances. In
      addition, there appear to be a number of potential variables that mediate the
      relationship between allergies and these two psychiatric phenomena (e.g.,
      allergies may heighten risk for these syndromes by triggering the immune system
      and cytokines; allergies may impair sleep through nasal obstruction and
      secondarily exacerbate psychiatric symptoms; and allergies may negatively affect
      cognitive functioning and contribute to psychiatric disturbance) as well as a
      possible shared genetic risk. The authors review and discuss these variables.

PMID- 21860843
TI  - How Adaptive Trial Designs can Increase Efficiency in Psychiatric Drug
      Development: A Case Study.
AB  - This paper uses a recently completed study to illustrate how adaptive trial
      designs can increase efficiency of psychiatric drug development. The design
      employed allowed a continuous reassessment of the estimated dose-response such
      that patients were randomized in a double-blind fashion to one of seven doses of
      the investigational drug, placebo, or active comparator. The study design also
      permitted early detection of futility allowing for early study termination. By
      using the adaptive trial design approach, only 202 patients were needed to make
      the determination of futility. In contrast, a conventional design would have
      required enrollment of 450 patients and considerably more time and expense to
      reach the same conclusion. Adaptive trial designs are important at this time when
      many pharmaceutical companies are abandoning the development of psychiatric
      medications because of the inefficiency of conventional approaches.

PMID- 21860842
TI  - Nonmedical treatment of patients with dementia.
AB  - This article reviews some nonmedical interventions that psychiatrists and other
      clinicians in the field of neuroscience can provide to their patients with
      dementia. The author discusses how clinicians can help patients and their
      caregivers understand the diagnosis causing the dementia (whether it be
      Alzheimer's, traumatic brain injury, Parkinson's disease, or vascular dementia)
      and help them to set realistic expectations of the treatment process for the
      patient and his or her loved ones. The author also reviews how clinicians can
      help caregivers modify their interactions with the patients when required to
      enhance not only the quality of life for the patient but the quality of life for
      the caregiver as well. Finally, the author reviews how clinicians can take on new
      initiatives that may help both the patients with dementia and their loved
      ones/caregivers when the patients are at the end stages of their disease.

PMID- 21860845
TI  - Four cases of takotsubo cardiomyopathy linked with exacerbations of psychiatric
      illness.
AB  - Objective. Takotsubo cardiomyopathy is a rare cardiac syndrome most often
      occurring in post-menopausal women after an acute episode of severe emotional or
      physical stress. Prior literature suggests a higher prevalence of anxiety and
      depression among patients with Takotsubo cardiomyopathy. We observed four cases
      of Takotsubo cardiomyopathy at one tertiary care center preceded by and
      concurrent with exacerbations of psychiatric illness rather than after acute
      episodes of stress. We examined each to further understand Takotsubo
      cardiomyopathy's pathogenesis and relationship to psychiatric illness.Methods. We
      retrospectively reviewed four consecutive cases of Takotsubo cardiomyopathy at
      one tertiary center from August 2009 to October 2009. The Diagnostic and
      Statistical Manual for Mental Disorders, Fourth Edition, Text Revision criteria
      were used to diagnose psychiatric illness. Each patient was diagnosed with
      Takotsubo cardiomyopathy via cardiac catheterization.Results. Each woman (age
      range 53-67 years) was previously diagnosed with psychiatric illness. Psychiatric
      illnesses were as follows: Alzheimer's dementia with psychotic features,
      adjustment disorder, major depressive disorder, and bipolar affective disorder
      type 1. All four cases demonstrated exacerbations of their psychiatric illness
      just prior to and concurrent with their diagnosis of Takotsubo cardiomyopathy.
      They showed improved left ventricular ejection fraction within 1 to 3 weeks after
      diagnosis with supportive care.Conclusions. Differing from the traditional cases
      of Takotsubo cardiomyopathy, which follow acute events of stress, our four cases
      indicate exacerbations of underlying psychiatric illness can lead to Takotsubo
      cardiomyopathy. In addition to anxiety and depression, psychosis and mania may
      predispose an individual to Takotsubo cardiomyopathy. We suggest that
      cardiologists and psychiatrists be aware of this association and screen patients.
      We suggest further studies that may help better understand the connection between
      the heart and mind.

PMID- 21860844
TI  - Prevalence and correlates of alpha-delta sleep in major depressive disorders.
AB  - Objective. Major depressive disorder is associated with sleep disturbances. An
      electroencephalographic pattern of alpha wave intrusion in delta wave sleep
      (alpha-delta sleep) is observed in some subjects with major depressive disorder.
      The treatment-resistant symptoms in major depressive disorder, nonrestorative
      sleep and fatigue, are associated with alpha-delta sleep. The objective of this
      study is to identify the prevalence and clinical correlates of alpha-delta sleep
      in major depressive disorder.Design. Retrospective studySetting. Sleep Disorders
      Center, Cleveland Clinic, Cleveland, OhioParticipants. Polysomnograms were
      conducted on 150 subjects 18 years of age or older (75 with and 75 without major
      depressive disorder) were reviewed.Measurements. The percent of delta waves with
      alpha intrusion was collected and analyzed.Results. Subjects with major
      depressive disorder compared to nondepressed subjects had a higher sleep
      efficiency (83.0+/-9.6; 78.1+/-8.2%), shorter rapid eye movement latency (85.0+/
      44.5; 189.9+/-25.6 min), less slow wave sleep (8.3+/-3.0; 13.5+/-6.2%), and
      greater rapid eye movement (24.7+/-7.0; 19.2+/-8.2%), and all of these findings
      were statistically significant. Patients with major depressive disorder had
      higher alpha-delta sleep (23.4+/-14.2%; 2.3+/-6.7%, p<0.01). Patients with major
      depressive disorder were categorized into high and low alpha-delta sleep based on
      percentage of alpha-delta sleep present in slow wave sleep (alpha-delta sleep was
      present >=15% or <=15% of slow wave sleep, respectively). Patients with major
      depressive disorder with high alpha-delta sleep were at 3.15 greater odds (1.22
      8.14; p=0.018) to have excessive daytime sleepiness.Conclusion. Patients with
      major depressive disorder have a higher prevalence of alpha-delta sleep. Alpha
      delta sleep is associated with daytime sleepiness in patients with major
      depressive disorder. Study limitations include the retrospective nature of the
      project and the fact that the principle investigator, who scored and interpreted
      alpha intrusion, was not blind to group membership.

PMID- 21860846
TI  - Thomas jefferson loved music.

PMID- 21860847
TI  - Colorimetric filtrations of metal chelate precipitations for the quantitative
      determination of nickel(II) and lead(II).
AB  - A colorimetric filtration method has been developed for the highly selective and
      sensitive determination of Ni(2+) and Pb(2+) ions. Determinations of Ni(2+) and
      Pb(2+) follow the filtration using nioxime (1,2-cyclohexanedione dioxime) and
      rhodizonic acid disodium salt, respectively, as colorimetric reagents. Different
      from regular instrumentation techniques, the metal chelate precipitations are
      continuously pumped into a home-made flow cell at a constant flow rate, and
      filtered by a cellulose acetate/nitrate membrane. The color changes of the
      membrane are imaged using a conventional flatbed scanner, and digitized. The
      special selection of individual channels in the red, green, and blue channels of
      the images filters the influences of coexisting ions and provides a highly
      selective detection of Ni(2+) and Pb(2+) cations. The linear relationship between
      the colorimetric response of the chosen channel and Ni(2+) or Pb(2+)
      concentrations indicates a quantitative detection. The detection limit for Pb(2+)
      is 3 MUM (almost half of the Chinese wastewater discharge standard
      concentration), and is well below the nM level (94 nM) for Ni(2+) (a quarter of
      the WHO drinking water safe-exposure standard for Ni(2+)). The determinations
      take five to ten minutes. No shelf life issue exists because the chelating
      indicators react with metal directly without any pre-immobilizations.

PMID- 21860848
TI  - Using a TEMPO-based fluorescent probe for monitoring oxidative stress in living
      cells.
AB  - Generation of too many reactive oxygen species (ROS) in relation to available
      antioxidants in living cells can cause oxidative stress, which is involved in the
      development and progression of several serious diseases. 2',7'
      Dichlorodihydrofluorescein (DCFH) and its diacetate form, DCFH-DA, are widely
      used probes for monitoring general oxidative stress in cells, but DCFH oxidation
      is not always related to ROS. We report here a new method for quantifying
      cellular oxidative stress using a 2,2,6,6-tetramethyl- piperidine-1-oxyl (TEMPO)
      based probe. We tested and verified the probe both in cell-free solutions and in
      living cells under conditions of increased or reduced oxidative stress. The probe
      revealed the oxidative stress status in living cells and may be a useful
      complement to DCFH fluorescent probes.

PMID- 21860849
TI  - A new family of "clicked" estradiol-based low-molecular-weight gelators having
      highly symmetry-dependent gelation ability.
AB  - Reported herein is the discovery of a novel family of "clicked" estradiol-based
      LMWGs whose gelation ability highly depends on the gelator symmetry. These LMWGs
      that gel different organic solvents in the presence of H(2)O even at
      concentrations as low as 0.04 wt% are readily accessible using "click" chemistry.

PMID- 21860850
TI  - An efficient synthesis of hydropyrido[1,2-a]indole-6(7H)-ones via an In(III)
      catalyzed tandem cyclopropane ring-opening/Friedel-Crafts alkylation sequence.
AB  - An efficient Lewis acid-catalyzed cyclopropane ring-opening/Friedel-Crafts
      alkylation sequence of methyl 1-(1H-indole-carbonyl)-1-cyclopropanecarboxylates
      is reported. The protocol affords functionalized hydropyrido[1,2-a]indole-6(7H)
      ones in up to 99% yield.

PMID- 21860851
TI  - Photoinduced hole trapping in single semiconductor quantum dots at specific sites
      at silicon oxide interfaces.
AB  - Blinking dynamics of CdSe/ZnS semiconductor quantum dots (QD) are characterized
      by (truncated) power law distributions exhibiting a wide dynamic range in
      probability densities and time scales both for off- and on-times. QDs were
      immobilized on silicon oxide surfaces with varying grades of hydroxylation and
      silanol group densities, respectively. While the off-time distributions remain
      unaffected by changing the surface properties of the silicon oxide, a deviation
      from the power law dependence is observed in the case of on-times. This deviation
      can be described by a superimposed single exponential function and depends
      critically on the local silanol group density. Furthermore, QDs in close
      proximity to silanol groups exhibit both high average photoluminescence
      intensities and large on-time fractions. The effect is attributed to an
      interaction between the QDs and the silanol groups which creates new or deepens
      already existing hole trap states within the ZnS shell. This interpretation is
      consistent with the trapping model introduced by Verberk et al. (R. Verberk, A.
      M. van Oijen and M. Orrit, Phys. Rev. B, 2002, 66, 233202).

PMID- 21860852
TI  - Theoretical study of the solvation of HgCl2, HgClOH, Hg(OH)2 and HgCl3(-): a
      density functional theory cluster approach.
AB  - The determination of the solvation shell of Hg(II)-containing molecules and
      especially the interaction between Hg(II) and water molecules is the first
      requirement to understand the transmembrane passage of Hg into the cell. We
      report a systematic DFT study by stepwise solvation of HgCl(2) including up to 24
      water molecules. In order to include pH and salinity effects, the solvation
      patterns of HgClOH, Hg(OH)(2) and HgCl(3)(-) were also studied using 24 water
      molecules. In all cases the hydrogen bond network is crucial to allow orbital
      driven interactions between Hg(II) and the water molecules. DFT Born-Oppenheimer
      molecular dynamics simulations starting from the stable HgCl(2)-(H(2)O)(24)
      structure revealed that an HgCl(2)-(H(2)O)(3) trigonal bipyramid effective solute
      appears and then the remaining 21 water molecules build a complete first
      solvation shell, in the form of a water-clathrate. In the HgCl(2), HgClOH,
      Hg(OH)(2)-(H(2)O)(24) optimized structures Hg also directly interacts with 3
      water molecules from an orbital point of view (three Hg-O donor-acceptor type
      bonds). All the other interactions are through hydrogen bonding. The cluster
      derived solvation energies of HgCl(2), HgClOH and Hg(OH)(2) are estimated to be 
      34.4, -40.1 and -47.2 kcal mol(-1), respectively.

PMID- 21860853
TI  - Spin crossover and polymorphism in a family of 1,2-bis(4-pyridyl)ethene-bridged
      binuclear iron(II) complexes. A key role of structural distortions.
AB  - Two polymorphic modifications 1 and 3 of binuclear compound
      [{Fe(dpia)(NCS)(2)}(2)(bpe)] and pseudo-polymorphic modification
      [{Fe(dpia)(NCS)(2)}(2)(bpe)].2CH(3)OH (2), where dpia = di-(2-picolyl)amine, bpe
      = 1,2-bis(4-pyridyl)ethene, were synthesized, and their structures, magnetic
      properties, and Mossbauer spectra were studied. Variable-temperature magnetic
      susceptibility measurements of three binuclear compounds show different types of
      magnetic behaviour. The complex 1 exhibits a gradual two-step spin crossover
      (SCO) suggesting the occurrence of the mixed [HS-LS] (HS: high spin, LS: low
      spin) pair at the plateau temperature (182 K), at which about 50% of the
      complexes undergoes a thermal spin conversion. The complex 2 displays an abrupt
      full one-step spin transition without hysteresis, centred at about 159 K. The
      complex 3 is paramagnetic over the temperature range 20-290 K. The single-crystal
      X-ray studies show that all three compounds are built up from the bpe-bridged
      binuclear molecules. The structure of 1 was solved for three spin isomers [HS
      HS], [HS-LS], and [LS-LS] at three temperatures 300 K, 183 K, and 90 K. The
      crystal structures for 2 and 3 were determined for the [HS-HS] complexes at room
      temperature. The analysis of correlations between the structural characteristics
      and different types of magnetic behaviour for new 1-3 binuclear complexes, as
      well as for previously reported binuclear compounds, revealed that the SCO
      process (occurrence of full one-step, two-step, or partial (50%) SCO) is
      specified by the degree of distortion of the octahedral geometry of the [FeN(6)]
      core, caused by both packing and strain effects arising from terminal and/or
      bridging ligands. The comparison of the magnetic properties and the networks of
      intra- and inter-molecular interactions in the crystal lattice for the family of
      related SCO binuclear compounds suggests that the intermolecular interactions
      play a predominant role in the cooperativeness of the spin transition relative to
      the intramolecular interactions through the bridging ligand.

PMID- 21860854
TI  - Environmental hazard of cadmium, copper, lead and zinc in metal-contaminated
      soils remediated by sulfosuccinamate formulation.
AB  - Accumulation of metals in soil at elevated concentrations causes risks to the
      environmental quality and human health for more than one hundred million people
      globally. The rate of metal release and the alteration of metal distribution in
      soil phases after soil washing with a sulfosuccinamate surfactant solution
      (Aerosol 22) were evaluated for four contaminated soils. Furthermore, a
      sequential extraction scheme was carried out using selective extractants (HAcO,
      NH(2)OH.HCl, H(2)O(2) + NH(4)AcO) to evaluate which metal species are extracted
      by A22 and the alteration in metal distribution upon surfactant-washing.
      Efficiency of A22 to remove metals varied among soils. The washing treatment
      released up to 50% of Cd, 40% of Cu, 20% of Pb and 12% of Zn, mainly from the
      soluble and reducible soil fractions, therefore, greatly reducing the fraction of
      metals readily available in soil. Metal speciation analysis for the solutions
      collected upon soil washing with Aerosol 22 further confirmed these results.
      Copper and lead in solution were mostly present as soluble complexes, while Cd
      and Zn were present as free ions. Besides, redistribution of metals in soil was
      observed upon washing. The ratios of Zn strongly retained in the soil matrix and
      Cd complexed with organic ligands increased. Lead was mobilized to more weakly
      retained forms, which indicates a high bioavailability of the remaining Pb in
      soil after washing. Comprehensive knowledge on chemical forms of metals present
      in soil allows a feasible assessment of the environmental impact of metals for a
      given scenario, as well as possible alteration of environmental conditions, and a
      valuable prediction for potential leaching and groundwater contamination.

PMID- 21860855
TI  - Penetration of polar brominated DBPs through the activated carbon columns during
      total organic bromine analysis.
AB  - Total organic bromine (TOBr) is a collective parameter representing all the
      brominated organic disinfection byproducts (DBPs) in water samples. TOBr can be
      measured using the adsorption-pyrolysis method according to Standard Method
      5320B. This method involves that brominated organic DBPs are separated from
      inorganic halides and concentrated from aqueous solution by adsorption onto the
      activated carbon (AC). Previous studies have reported that some commonly known
      brominated DBPs can partially penetrate through the AC during this adsorption
      step. In this work, the penetration of polar brominated DBPs through AC and ozone
      modified AC was explored with two simulated drinking water samples and one
      chlorinated wastewater effluent sample. Polar brominated DBPs were selectively
      detected with a novel precursor ion scan method using electrospray ionization
      triple quadrupole mass spectrometry. The results show that 3.4% and 10.4% of
      polar brominated DBPs (in terms of total ion intensity) in the chlorinated
      Suwannee River fulvic acid and humic acid samples, respectively, penetrated
      through the AC, and 19.6% of polar brominated DBPs in the chlorinated secondary
      wastewater effluent sample penetrated through the AC. The ozone-modification of
      AC minimized the penetration of polar brominated DBPs during the TOBr analysis.

PMID- 21860856
TI  - Antioxidative, antibrowning and antibacterial activities of sixteen floral
      honeys.
AB  - Commonly consumed honeys from sixteen different single floral sources were
      analyzed for their in vitro antioxidant capacities by several methods including
      DPPH, ABTS, FRAP, SASR and MDA assays. The total polyphenol contents varied among
      the tested honeys and were highly correlated to their antioxidant capacity
      values. The antioxidant capacity of Chinese milk vetch flower honeys was
      significantly higher than those of other flower honeys. All honeys tested were
      active in inhibiting the browning of apple homogenate and linden honey displayed
      the highest inhibition rate as 85%. When the antimicrobial activity of the
      investigated honeys was screened using Gram-positive bacteria (Staphylococcus
      aureus) and Gram-negative bacteria (Escherichia coli), clover honey exhibited the
      strongest antibacterial activity as 2.2 mg mL(-1) kanamycin equivalent
      inhibition.

PMID- 21860857
TI  - Synthesis of spiroketals under neutral conditions via a type III ring
      rearrangement metathesis strategy.
AB  - A conceptually novel approach to spiro- and dispiroketals of various ring-sizes
      under neutral conditions has been designed which complements the classical
      thermodynamically driven tactic. Key steps involved the formation of alpha
      alkoxyfurans, their [4+2] or [4+3] cycloaddition reactions and the ring
      rearrangement metathesis of the resulting oxabicycles.

PMID- 21860858
TI  - Tools for micropatterning epithelial cells into microcolonies on transwell filter
      substrates.
AB  - Despite the importance of epithelial tissue in most major organs there have been
      limited attempts to tissue engineer artificial epithelium. A key feature of
      mature epithelium is the presence of an apical-basal polarization, which develops
      over 7-20 days in culture. Currently, the most widely used 2D system to generate
      polarized epithelium in vitro involves the filter insert culture system, however
      this system is expensive, laborious and requires large numbers of cells per
      sample. We have developed a set of micropatterning techniques to spatially
      control the organization of epithelial cells into microsheets on filter inserts
      under the culture conditions necessary to induce epithelial cell polarization.
      Micropatterning improves cell uniformity within each microsheet, allows multiple
      sheet analysis on one filter insert, and reduced cell number requirements. We
      describe an agarose patterning method that allows maintenance of cell patterns
      for over 15 days, the time necessary to induce apical-basal polarization. We also
      describe a ParafilmTM patterning method that allows patterning for 5 to 15 days
      depending on cell type and only allows the generation of stripes and circular
      microsheets. The parafilmTM method however is extremely straightforward and could
      be easily adopted by any laboratory without the need of access to specialized
      microfabrication equipment. We also demonstrate that micropatterning epithelial
      cells does not alter the localization of the apical-basal marker ZO-1 or the
      formation of cilia, a marker of epithelium maturation. Our methods provide a
      novel tool for studying epithelial biology in polarized epithelium microsheets of
      controlled size.

PMID- 21860859
TI  - Structural change of metallofullerene: an easier thermal decomposition.
AB  - We have studied for the first time the structural change of high-purity
      metallofullerene (Gd@C(82)) upon heat treatment in an ultra-high vacuum system
      (10(-10) Torr) and examined the decomposition product through successive analysis
      with MS, IR, Raman, TEM, EDS and XPS. It was found that metallofullerene
      (Gd@C(82)) had fully collapsed at 580  degrees C which was lower than that for
      the complete destruction of C(60). The easier decomposition should be ascribed to
      the encapsulated metal in the carbon cage which could induce the deformation of
      the C-C bond. The analysis indicated that the broken metallofullerene (Gd@C(82))
      became a kind of graphite-like material with a lot of defects. The Gd atoms
      leaked out from the carbon cage and aggregated together to form a regular
      arrangement.

PMID- 21860860
TI  - A tri-layer structure consisting of novel heptacobaltate clusters and single
      cobalt centers bridged by 5-tert-butyl isophthalate.
AB  - A 2D tri-layer compound {[Co(8)(tbip)(6)(H(2)O)(9)(OH)(4)].12(H(2)O)}(n) (1)
      (H(2)tbip = 5-tert-butyl isophthalic acid) consisting of novel heptacobaltate
      clusters and single cobalt centers bridged by tbip(2-) ligands has been
      hydrothermally synthesized. The complex represents a rare example of a
      homometallic coordination polymer built up from both heptanuclear metal clusters
      and single metal centers simultaneously. The magnetic investigation reveals that
      the complex exhibits the overall predominance of antiferromagnetic coupling
      between magnetic centers.

PMID- 21860861
TI  - Phosphirenium-borate zwitterion: formation in the 1,1-carboboration reaction of
      phosphinylalkynes.
AB  - Reaction of the acetylene Mes(2)P-C=C-Ar with B(C(6)F(5))(3) at rt gives a
      zwitterionic phosphirenium product, which reacts further at >100  degrees C to
      complete the 1,1-carboboration reaction.

PMID- 21860862
TI  - Structure-activity relationships for organometallic osmium arene
      phenylazopyridine complexes with potent anticancer activity.
AB  - We report the synthesis and characterisation of 32 half sandwich
      phenylazopyridine Os(II) arene complexes [Os(eta(6)
      arene)(phenylazopyridine)X](+) in which X is chloride or iodide, the arene is p
      cymene or biphenyl and the pyridine and phenyl rings contain a variety of
      substituents (F, Cl, Br, I, CF(3), OH or NO(2)). Ten X-ray crystal structures
      have been determined. Cytotoxicity towards A2780 human ovarian cancer cells
      ranges from high potency at nanomolar concentrations to inactivity. In general
      the introduction of an electron-withdrawing group (e.g. F, Cl, Br or I) at
      specific positions on the pyridine ring significantly increases cytotoxic
      activity and aqueous solubility. Changing the arene from p-cymene to biphenyl and
      the monodentate ligand X from chloride to iodide also increases the activity
      significantly. Activation by hydrolysis and DNA binding appears not to be the
      major mechanism of action since both the highly active complex [Os(eta(6)-bip)(2
      F-azpy)I]PF(6) (9) and the moderately active complex [Os(eta(6)-bip)(3-Cl
      azpy)I]PF(6) (23) are very stable and inert towards aquation. Studies of octanol
      water partition coefficients (log P) and subcellular distributions of osmium in
      A2780 human ovarian cancer cells suggested that cell uptake and targeting to
      cellular organelles play important roles in determining activity. Although
      complex 9 induced the production of reactive oxygen species (ROS) in A2780 cells,
      the ROS level did not appear to play a role in the mechanism of anticancer
      activity. This class of organometallic osmium complexes has new and unusual
      features worthy of further exploration for the design of novel anticancer drugs.

PMID- 21860863
TI  - Redox tunable reversible molecular sieves: orthorhombic molybdenum vanadium
      oxide.
AB  - We demonstrated that the sorption behavior of orthorhombic Mo-V oxide
      (Mo(29)V(11)O(112-x)) is continually and reversibly tunable by redox treatment.

PMID- 21860864
TI  - The residence probability: single molecule fluorescence correlation spectroscopy
      and reversible geminate recombination.
AB  - The residence probability of a freely diffusing particle within an open d
      dimensional ball is calculated as a function of time, for an initial distribution
      that is either a spherical delta function or uniform within the sphere. The
      latter is equivalent to the autocorrelation function (ACF) of fluorescence
      correlation spectroscopy (FCS) when utilizing near-field scanning optical
      microscopy (NSOM) probes. Starting from the general equation for the Laplace
      transform of the residence probability, we solve it in Laplace space for any
      dimensionality, inverting it into the time domain in one- and three-dimensions.
      The short- and long-time asymptotic behaviors of the residence probability are
      derived and compared with the exact results. Approximations for the two
      dimensional ACF are discussed, and a new approximation is derived for the NSOM
      FCS ACF. Also of interest is an analytic expression for a three-dimensional ACF,
      which could be useful for two-photon FCS. Analogy with the binding probability
      for reversible geminate recombination suggests that more information could be
      extracted from the long-time tails in FCS experiments.

PMID- 21860865
TI  - How to control the scaling of CaCO3: a "fingerprinting technique" to classify
      additives.
AB  - A titration set-up coupling ion selective electrodes with pH adjustment was used
      to analyze the effects of additives present during precipitation of calcium
      carbonate. Besides industrially well-established antiscalants (sodium
      triphosphate, citrate, polyacrylate and poly(aspartic acid)), also functional
      polymers being active in morphosynthesis (polystyrene sulfonate and poly(styrene
      alt-maleic acid)) were analyzed. Interestingly each additive acts in its specific
      way, suggesting the notation "fingerprinting" for a complex interplay of up to
      five "solution modes" of influencing CaCO(3) precipitation and crystallisation.
      The results provide new insights into the modes of additive controlled
      crystallisation, and in the long run, the insights may facilitate the design of
      precipitation systems that yield complex and tailor-made crystals.

PMID- 21860866
TI  - A molecular dynamics study of 1,1-diamino-2,2-dinitroethylene (FOX-7) crystal
      using a symmetry adapted perturbation theory-based intermolecular force field.
AB  - A dimer potential energy function for 1,1-diamino-2,2-dinitroethylene (FOX-7) has
      been developed using symmetry adapted perturbation theory based on a Kohn-Sham
      density functional theory description of the monomers [SAPT(DFT)]. Interaction
      energies of 1008 dimer configurations were computed in an augmented double zeta
      basis set and fitted to an atom-atom intermolecular potential energy function of
      Coulomb plus Buckingham exp-6 form. The potential was used in isothermal
      isostress molecular dynamics simulations to study the structure and
      thermal/pressure response of FOX-7 crystal. The simulated structure is in very
      good agreement with experiment and the computed thermal/pressure response of the
      crystal shows significant anisotropy with respect to crystallographic direction,
      in-line with experimental observations. It is concluded that SAPT(DFT) is an
      excellent method for development of intermolecular potentials for energetic
      molecular crystals.

PMID- 21860867
TI  - From microscopic insights of H2 adsorption to uptake estimations in MOFs.
AB  - The adsorption of hydrogen in MOFs takes place mainly close to the inorganic
      secondary building unit (IBU). The adsorption capacities on MIL-88, UiO-66, MIL
      47 and MFU-1 were investigated. Quantum chemical calculations at the ab initio
      HF/MP2 theoretical level were employed to estimate the maximum uptake of H(2)
      molecules per metallic centre. Extrapolating the results on small clusters to the
      unit cell of each particular MOF, the H(2) uptakes (gravimetric and volumetric)
      were estimated. The loading of hydrogen per metal atom (H(2) molecules/M-atom)
      and the density of metal atoms (M-atoms A(-3)) were defined as useful parameters
      to assess hydrogen storage properties and to estimate the optimum density that
      the material should have to be a good H(2) adsorbent. It was found that values
      above 3 H(2) molecules/M-atom and around 0.004 M-atoms A(-3) for MOFs with
      densities around 0.7-1.0 g cm(-3) are required to reach the 2015 storage targets.

PMID- 21860868
TI  - Determination of the relevant magnetic interactions in low-dimensional molecular
      materials: the fundamental role of single crystal high frequency EPR.
AB  - A new one-dimensional copper(II) complex with formula [Cu(hfac)(2)(N(3)TEMPO)](n)
      (hfac = hexafluoroacetylacetonate and N(3)TEMPO = 4-azido-2,2,6,6
      tetramethylpiperidine-1-oxyl) has been synthesized and investigated by X-ray
      crystallography, magnetometry and multifrequency single crystal EPR. The system
      crystallizes in the P1 space group with two non equivalent copper(II) ions in the
      unit cell, the two nitroxide radicals being coordinated to Cu(1) in axial
      positions. The copper(II) ions are bridged by N(3)TEMPO radicals resulting in a
      zig-zag chain structure. The magnetic susceptibility data were at first
      satisfactorily modeled assuming an alternating spin chain along the
      monodimensional covalent skeleton, with a ferromagnetic interaction between Cu(1)
      and the nitroxide moieties and a weaker antiferromagnetic interaction between
      these and Cu(2) (J(1) = -13.8 cm(-1), J(2) = +2.4 cm(-1)). However, single
      crystal EPR studies performed at the X- and W-band clearly demonstrate that the
      observed magnetic monodimensional character of the complex is actually due to the
      intermolecular contacts involving N(3)TEMPO ligands. This prompted us to fit the
      magnetic data using a consistent model, pointing out the fundamental role of
      single crystal EPR data in defining a correct model to describe the magnetic
      properties of molecular low dimensional systems.

PMID- 21860869
TI  - Phosphine and solvent effects on oxidative addition of CH3Br to Pd(PR3) and
      Pd(PR3)2 complexes.
AB  - The reaction between bromomethane CH(3)Br and Pd(0) phosphine complexes Pd(PR(3))
      and Pd(PR(3))(2) resulting in the corresponding Pd(II) species Pd(PR(3))(CH(3))Br
      and Pd(PR(3))(2)(CH(3))Br was studied computationally with DFT methods. The
      oxidative addition can take place through two different mechanisms: concerted or
      S(N)2 transition state. The effect of a number of variables on the height of the
      barrier associated to each of these two mechanisms is systematically analyzed.
      The variables considered include the number of ligands on the metal (mono- or bis
      phosphine), the nature of the phosphine (PF(3), PH(3), PMe(3) or PPh(3)), and the
      nature of the solvent (gas phase, tetrahydrofuran or dimethylformamide). A number
      of trends can be identified, resulting in a complex picture where the nature of
      the phosphine and the solvent can be tuned to favor one of the two possible
      mechanisms, with the corresponding stereochemical implications that can be
      extrapolated to the behaviour of more sophisticated substrates.

PMID- 21860870
TI  - Kinetics and reversibility of micropollutant sorption in sludge.
AB  - The fate of micropollutants throughout wastewater treatment systems is highly
      dependent on their sorption interactions with sludge matter. In this study, both
      the sorption and desorption kinetics of polycyclic aromatic hydrocarbons (PAHs)
      in activated sludge were shown to be very rapid in comparison to biodegradation
      kinetics. It was concluded that PAH transfer does not limit their biodegradation
      and that their fate is governed by the sorption/desorption equilibrium state. The
      effect of contact time between sludge and PAHs was also investigated. It was
      shown that aging did not influence the sorption/desorption equilibrium although
      PAH losses during aging suggest that sequestration phenomena had occurred. This
      implies that for PAH sorption assessment within treatment processes there is no
      need to include a contact time dimension. As a consequence, thanks to an
      innovative approach taking into account sorption equilibria and sequestration,
      this work has demonstrated that studies in the literature which, in main, deal
      with micropollutant sorption in sewage sludge with only a short contact time can
      be extrapolated to real systems in which sorption, desorption and aging occur.

PMID- 21860872
TI  - UVA photosensitization of thiopurines and skin cancer in organ transplant
      recipients.
AB  - The thiopurines azathioprine, 6-mercaptopurine and 6-thioguanine (6-TG) are
      important medications for cancer and inflammatory disorders. They are also widely
      prescribed as immunosuppressants in organ transplant patients. Their metabolism
      results in the incorporation of 6-TG into patients' DNA, and this increases skin
      sensitivity to incident UVA. Unlike the canonical DNA bases, which do not absorb
      UVA to a significant degree, DNA 6-TG is a strong UVA chromophore. It acts as a
      Type II UVA photosensitizer, and the combination of 6-TG and UVA treatment
      induces a synergistic toxicity in cultured human cells. Here, we review some of
      the damage that this interaction causes. Photochemical activation of DNA 6-TG
      triggers DNA and protein oxidation; it induces DNA breakage, DNA crosslinking,
      oxidation of DNA bases and the covalent attachment of proteins to DNA. Many of
      these photochemical DNA lesions are difficult for cells to deal with, and we
      review the evidence linking thiopurine immunosuppression with genome instability
      and the high incidence of skin cancer in organ transplant recipients.

PMID- 21860873
TI  - Structural adjustment during intercalation of macrocyclic crown ether into LDH
      via swelling/restoration reaction: staging formation and mechanism insights.
AB  - The structural control involving staging formation was studied in the
      nanocomposites of macrocyclic tetraazacrown ether carboxylic acid derivative
      (TECA) and layered double hydroxide (LDH) obtained by an osmotic
      swelling/restoration process. After NO(3)-type MgAl-LDH was osmotically swollen
      in formamide, TECA was added, leading to a restoration of the LDH sheets and
      formation of TECA-LDH nanocomposites. In the wet state, the structure of the
      composites was homogenous, and the basal spacings of ~2.0 or 1.8 nm were not
      changed by the water-washing process that removed formamide and caused the
      replacement of NO(3)(-) by CO(3)(2-). However, in the drying process, both the
      orientation of TECA in the interlayer and the formed staging structure varied
      with the TECA content. The TECA orientation changed from horizontal to
      tilted/twisted and finally to vertical with interlayer TECA density. The staging
      structure occurred for samples with both TECA and small inorganic guests
      coexisting in the interlayer. Third-staging, second-staging, and homogenous
      structures were observed at TECA/LDH weight ratios of low (0.125 and 0.25),
      medium (0.5) and large (1 and 2) values, respectively. The decrease of negative
      charge of TECA ions from -4 to -1 led to the co-existence of small ions (NO(3)(
      )) with TECA in the gallery and the formation of a NO(3)(-)-containing staging
      structure, even at a high TECA/LDH ratio of 2. The study of the influence of
      CO(3)(2-) on the composite structure indicates that a TECA/CO(3)(2-) ion exchange
      progressed reversibly and the staging structure formed is thermodynamically
      stable, depending mainly on the chemical composition of the interlayer guests.
      The staging formation could be explained by the Daumas-Herold model, which
      differs markedly from the Rudorff model previously proposed for the LDH system.
      The treatment in formamide of the composite such as T2L+Na(2)CO(3) with staging
      structure shows that the transformation process is reversible, and these kinds of
      composites may be used as an adsorbent for some harmful organic solvents.

PMID- 21860875
TI  - Reconsideration of the anomalous dielectric behavior of dimethyl sulfoxide in the
      pure liquid state.
AB  - Although many vibrational spectroscopic studies using infrared absorption and
      Raman scattering techniques reveal that dimethyl sulfoxide (DMSO) forms
      intermolecular associations, such as dimers, in the pure liquid state, the
      results of many dielectric relaxation studies deny the presence of such
      associations and claim very little orientational correlation between the dipoles
      of DMSO molecules because of a Kirkwood correlation factor close to unity in the
      pure liquid state and in solution. Recently, we found reasons for the
      inconsistency and elucidated the presence of dimeric DMSO associations via
      dielectric relaxation measurements from 50 MHz to 50 GHz. The dissociation of
      DMSO dimers is the major dielectric relaxation process with a relaxation time of
      19 ps, while the relaxation of monomeric DMSO is a minor mode with a relaxation
      time of 4.5 ps at 25  degrees C and slightly increasing strength with increasing
      temperature.

PMID- 21860876
TI  - Occurrence and distribution of benzothiazole in the Schwarzbach watershed
      (Germany).
AB  - This study quantifies the regional distribution of the micropollutant
      benzothiazole (BT) in river water by sampling 15 river sites in the Schwarzbach
      watershed (about 400 km(2)) from November 2008 to February 2010. Additionally,
      wastewater samples from three municipal wastewater treatment plants (WWTPs) in
      Germany were analyzed. BT was detected in all wastewater influent and effluent
      samples as well as in all river water samples collected downstream of wastewater
      discharge. This corroborates the ubiquitous occurrence of BT in the aqueous
      environment. Concentrations were between 58 and 856 ng L(-1) in the river water.
      The observed mean concentration at the outlet of the investigated catchment was
      109 ng L(-1). With only a few exceptions, temporal and spatial variations of BT
      concentrations in river water were low. Rather similar BT concentrations over a
      wide range of river discharge indicate that dilution along the mainstream is
      negligible and, thus, supports the hypothesis that paved surface runoff during
      rain events is an important BT source not only for wastewater influent but also
      for river water. This was supported by detecting the highest BT concentrations at
      sampling locations close to the dense highway network around the city of
      Frankfurt. Since BT was also detected in river water collected from locations
      that were clearly unaffected by wastewater effluent discharge, surface runoff
      must be considered as a diffuse source of BT in river water.

PMID- 21860877
TI  - S-nitrosocaptopril formation in aqueous acid and basic medium. A vasodilator and
      angiotensin converting enzyme inhibitor.
AB  - The reaction of S-nitrosocaptopril (NOcap) formation was studied in both aqueous
      acid and basic medium. Captopril (cap) reacts rapidly with nitrous acid in strong
      acid medium to give the stable--in the timescale of the experiments--NOcap. The
      kinetic study of the reaction involving the use of stopped-flow, shows that at
      low sodium nitrite (nit) concentration, the reaction is first-order in both
      [nit], [H(+)], and is strongly catalysed by Cl(-) or Br(-) (= X(-)): rate = (k(3)
      + k(4)[X(-)])[H(+)][nit][cap]. In aqueous buffered solution of acetic acid
      acetate the reaction rate is much slower and the decomposition of NOcap was
      observed; however, the rate of NOcap decay is more than 30-fold slower than its
      formation. In aqueous basic medium of carbonate-hydrogen carbonate buffer, as
      well as in alkaline medium, the kinetics of the nitroso group (NO) transfer from
      tert-butyl nitrite (tBN) to cap was studied using either conventional or stopped
      flow methods. In mild basic medium, the NOcap decomposes. The NOcap formation is
      first-order in both tBN and cap concentrations, and the reaction rate increases
      with pH until to, approximately, pH 11.5, above which value it becomes pH
      independent or even invariable with the [OH(-)]. Kinetic results show that the
      thiolate ion of cap is the reactive species. In fact, the presence of anionic
      micelles of sodium dodecyl sulfate (SDS) inhibits the reaction due to the
      separation of the reagents; whereas, cationic micelles of
      tetradecyltrimethylammonium bromide (TTABr) catalyse the reaction at low
      surfactant concentration due to reagents concentration in the small volume of the
      micelle. The rate equation is: rate = k(f) K(SH)[cap][tBN]/(K(SH) + [H(+)]). The
      rate of NOcap decomposition in mild basic medium is first-order in both [cap] and
      [NOcap], and decreases on increasing pH; but, in alkaline medium the NOcap is
      stable within the timescale of the experiments. Based on the results, the NOcap
      decomposition yields the disulfide compound that is formed in the nucleophilic
      attack of the -SH group of cap to the sulfur electrophilic center of NOcap, -S
      N=O. The resulting rate equation is: rate = k(d)[H(+)][cap][NOcap]/(K(SH) +
      [H(+)]).

PMID- 21860878
TI  - Regio- and stereoselective synthesis of truncated 3'-aminocarbanucleosides and
      their binding affinity at the A3 adenosine receptor.
AB  - The stereoselective synthesis of truncated 3'-aminocarbanucleosides 4a-d via a
      stereo- and regioselective conversion of a diol 9 to bromoacetate 11a and their
      binding affinity towards the human A(3) adenosine receptor are described.

PMID- 21860879
TI  - Enrichment and aggregation of topological motifs are independent organizational
      principles of integrated interaction networks.
AB  - Topological network motifs represent functional relationships within and between
      regulatory and protein-protein interaction networks. Enriched motifs often
      aggregate into self-contained units forming functional modules. Theoretical
      models for network evolution by duplication-divergence mechanisms and for network
      topology by hierarchical scale-free networks have suggested a one-to-one relation
      between network motif enrichment and aggregation, but this relation has never
      been tested quantitatively in real biological interaction networks. Here we
      introduce a novel method for assessing the statistical significance of network
      motif aggregation and for identifying clusters of overlapping network motifs.
      Using an integrated network of transcriptional, posttranslational and protein
      protein interactions in yeast we show that network motif aggregation reflects a
      local modularity property which is independent of network motif enrichment. In
      particular our method identified novel functional network themes for a set of
      motifs which are not enriched yet aggregate significantly and challenges the
      conventional view that network motif enrichment is the most basic organizational
      principle of complex networks.

PMID- 21860881
TI  - A highly efficient TBAF-promoted intramolecular cyclization of gem-dibromoolefins
      for the synthesis of 2-bromobenzofurans(thiophenes).
AB  - A highly efficient tetra-(n-butyl)ammonium fluoride (TBAF)-promoted
      intramolecular cyclization of gem-dibromoolefins has been developed for the
      synthesis of 2-bromobenzofused heterocycles. The reaction provides a convenient
      approach to 2-bromobenzofurans(thiophenes) from the corresponding readily
      available gem-dibromovinyl substrates without a metal.

PMID- 21860880
TI  - Regiocontrolled aerobic oxidative coupling of indoles and benzene using Pd
      catalysts with 4,5-diazafluorene ligands.
AB  - Palladium-catalyzed aerobic oxidative cross-couplings of indoles and benzene have
      been achieved by using 4,5-diazafluorene derivatives as ancillary ligands. Proper
      choice of the neutral and anionic ligands enables control over the reaction
      regioselectivity.

PMID- 21860882
TI  - Interfacial assembly of cinnamoyl-terminated bolaamphiphiles through the
      air/water interface: headgroup-dependent assembly, supramolecular nanotube and
      photochemical sewing.
AB  - A series of cinnamoyl-terminated bolaamphiphiles were synthesized and their
      assemblies at the air/water interface were investigated. It was found that the
      assembly behaviour depended on the substituted groups on the cinnamoyl unit. The
      bolaamphiphile with 4-hydroxycinnamoyl head groups (HCDA) was found to assemble
      into a supramolecular nanotube, while the others formed only layer-structured
      films. Moreover, the nanotube formed from HCDA showed supramolecular chirality
      due to the symmetry breaking. Both the layered films and the nanotubes showed
      photochemical dimerization upon UV irradiation, which were studied from the UV
      Vis, FT-IR spectral and MALDI-TOF MS analysis. Interestingly, such dimerization
      behavior of the cinnamoyl group could be used to stabilize the nanotube of
      HCDAvia photochemical sewing. During such a process both the supramolecular
      chirality and the tubular shapes were kept. Remarkably, such a photochemical
      sewed chiral nanotube could further induce the chirality of an achiral porphyrin
      derivative assembled on it, and produced the induced chirality without using any
      chiral molecules.

PMID- 21860883
TI  - A magnetically controlled MEMS device for drug delivery: design, fabrication, and
      testing.
AB  - We report the development of a magnetically controlled drug delivery device for
      on-demand drug release to treat chronic diseases. The devices consist of drug
      loaded micro-reservoirs (6 mm in diameter and ~550 MUm in depth), sealed by
      magnetic PDMS (polydimethylsiloxane) membranes (O 6 mm * 40 MUm) with laser
      drilled apertures and actuated by an external magnetic field. We present a
      detailed analysis of the magnetic actuation forces and provide an estimate of the
      resulting membrane deflections. The reservoirs are fabricated by PDMS molding and
      loaded with drugs using solvent evaporation methods. Post-processing procedures
      using bovine serum albumin (BSA) adsorption on magnetic PDMS surfaces are carried
      out to modify the surface wettability and to allow water filling and dissolution
      of the drugs in the reservoirs. Detailed surface modification processes are
      described and characterized. The device demonstrates on-demand delivery of
      methylene blue (MB) as a model drug. Intermittent magnetic actuations of the
      device in a ~200 mT magnetic field show 10-fold increase in MB release compared
      to background release when the device is not actuated.

PMID- 21860884
TI  - TADAA: Towards Automated Detection of Anaesthetic Activity.
AB  - BACKGROUND: Task analysis is a valuable research method for better understanding
      the activity of anaesthetists in the operating room (OR), providing evidence for
      designing and evaluating improvements to systems and processes. It may also
      assist in identifying potential error paths to adverse events, ultimately
      improving patient safety. Human observers are the current 'gold standard' for
      capturing task data, but they are expensive and have cognitive limitations.
      OBJECTIVES: Towards Automated Detection of Anaesthetic Activity (TADAA)--aims to
      produce an automated task analysis system, employing Radio Frequency
      Identification (RFID) technology to capture anaesthetists' location, orientation
      and stance (LOS). This is the first stage in a scheme for automatic detection of
      activity. METHODS: Active RFID tags were attached to anaesthetists and various
      objects in a high fidelity OR simulator, and anesthetic procedures performed. The
      anaesthetists' LOSs were calculated using received signal strength (RSS)
      measurements combined with machine learning tools including Self-Organizing Maps
      (SOMs). These LOSs were compared to those derived from video recordings. RESULTS:
      SOM clustering was effective at determining anaesthetists' LOS from RSS data for
      each procedure. However cross-procedure comparison was less reliable,probably
      because of changes in the environment. CONCLUSIONS: Active RFID tags provide
      potentially useful information on LOS at a low cost and with minimal impact on
      the work environment. Machine learning techniques may be employed to handle the
      variable nature of RFID's radio signals. Work on mapping LOS data to activities
      will involve integration with other sensors and task analysis techniques.

PMID- 21860885
TI  - Hepatitis B marker seroprevalence and vaccination coverage in adolescents in the
      City of Itajai, State of Santa Catarina, Southern Brazil, in 2008.
AB  - INTRODUCTION: Hepatitis B infection constitutes an important cause of morbidity
      and mortality worldwide. In Brazil, however, the current epidemiological
      situation is not clear. Considering the importance of establishing this
      prevalence, the aim of this study was to determine the prevalence of HBV markers
      in voluntary adolescents, junior high (secondary school) students, in the City of
      Itajai, State of Santa Catarina, Brazil. METHODS: A seroepidemiological,
      transverse study was conducted with 353 randomly chosen adolescents from
      elementary school in 2008. Blood samples were analyzed for HBsAg, anti-HBc and
      anti-HBs. All analyses were conducted by automated microparticle enzyme
      immunosorbent assay (Abbott(r), AxSYM system, Deerfield, IL, USA), according to
      the manufacturer's instructions. RESULTS: The prevalence of HBsAg was 0.6% (CI
      95% 0.1 - 2.0), that of anti-HBc was 1.1% (CI 95% 0.3 - 2.9) and that of
      detectable anti-HBs was 83.6% (CI 95% 79.3 - 87.3). Hepatitis B vaccination
      coverage was 97.5% (CI 95% 95.2 - 98.8). CONCLUSIONS: These results demonstrate
      the success of the vaccination program against hepatitis B in the region studied
      and indicate that prevention strategies must be maintained and, if possible,
      expanded to contribute to the establishment of positive prevalence rates in all
      age groups.

PMID- 21860886
TI  - Lipodystrophy in HIV/AIDS patients with different levels of physical activity
      while on antiretroviral therapy.
AB  - INTRODUCTION: Lipodystrophy is related to the use of highly active antiretroviral
      therapy (HAART) and can cause aesthetic stigma and increase the risk of
      developing cardiovascular diseases. Physical activity may be a valid alternative
      for the treatment and prevention of lipodystrophy. However, few studies address
      this issue. The objective of this study was to assess lipodystrophy related to
      highly active antiretroviral therapy in HIV/AIDS patients with different physical
      activity habits. METHODS: The sample was composed of 42 HIV/AIDS patients taking
      HAART medication who were visiting the Counseling and Testing Center (CTC) in
      Presidente Prudente. The level of physical activity was obtained using the
      International Physical Activity Questionnaire (IPAQ); lipodystrophy was diagnosed
      using a self-report questionnaire that was administered to the patient and then
      followed up by medical confirmation. The percentage of trunk fat was estimated by
      dual X-Ray absorptiometry (DEXA). Information about sex, age, length of HAART
      treatment, CD4+ T lymphocyte count (CD4) and viral load was also collected.
      RESULTS: A higher prevalence of lipodystrophy was observed in the sedentary group
      when compared to the physically active group, which indicates that physical
      activity may be a protective factor in relation to the occurrence of
      lipodystrophy. The group that had a higher CD4 had a higher proportion of
      lipodystrophy and a higher proportion of younger and physically active
      individuals. The patients with lipodystrophy had a higher percentage of trunk fat
      and were more sedentary than active individuals. CONCLUSIONS: A physically active
      lifestyle has a protective effect against the occurrence of lipodystrophy related
      to HAART.

PMID- 21860887
TI  - Frequency of metabolic syndrome and the food intake patterns in adults living in
      a rural area of Brazil.
AB  - INTRODUCTION: Metabolic syndrome (MetS), a risk factor for atherosclerosis and
      coronary heart disease, is related to an inadequate food intake pattern. Its
      incidence is increasing among Brazilian adults, including those living in rural
      areas. Our aim was not only to describe the frequency of MetS in adults with or
      without MetS but also to compare their food intake pattern as assessed by the
      healthy eating index (HEI) and serum albumin and C reactive protein (CRP) levels.
      METHODS: Men and women (n = 246) living in a small village in Brazil were
      included. MetS was characterized according to the adult treatment panel (ATP III)
      criteria. Groups were compared by chi-square, student t or Mann-Whitney tests.
      RESULTS: MetS was diagnosed in 15.4% of the cases. The MetS group showed higher
      CRP (1.8+/-1.2 vs. 1.0+/-0.9 mg/dl) and lower albumin (4.3+/-0.3 vs. 4.4+/-0.3
      g/dl) serum levels compared to the control group. Additionally, the MetS group
      showed lower scores (median[range]) in the HEI compared to the control group
      (53.5[31.2-78.1] vs 58[29.7-89.5], respectively). The MetS group also had
      decreased scores for total fat and daily variety of food intake. CONCLUSIONS: The
      results suggest that adults with MetS displayed chronic mild inflammation and a
      poorer food intake pattern than the control group.

PMID- 21860888
TI  - A SARIMA forecasting model to predict the number of cases of dengue in Campinas,
      State of Sao Paulo, Brazil.
AB  - INTRODUCTION: Forecasting dengue cases in a population by using time-series
      models can provide useful information that can be used to facilitate the planning
      of public health interventions. The objective of this article was to develop a
      forecasting model for dengue incidence in Campinas, southeast Brazil, considering
      the Box-Jenkins modeling approach. METHODS: The forecasting model for dengue
      incidence was performed with R software using the seasonal autoregressive
      integrated moving average (SARIMA) model. We fitted a model based on the reported
      monthly incidence of dengue from 1998 to 2008, and we validated the model using
      the data collected between January and December of 2009. RESULTS: SARIMA (2,1,2)
      (1,1,1)12 was the model with the best fit for data. This model indicated that the
      number of dengue cases in a given month can be estimated by the number of dengue
      cases occurring one, two and twelve months prior. The predicted values for 2009
      are relatively close to the observed values. CONCLUSIONS: The results of this
      article indicate that SARIMA models are useful tools for monitoring dengue
      incidence. We also observe that the SARIMA model is capable of representing with
      relative precision the number of cases in a next year.

PMID- 21860889
TI  - Nosocomial infection and characterization of extended-spectrum beta-lactamases
      producing Enterobacteriaceae in Northeast Brazil.
AB  - INTRODUCTION: Extended spectrum beta-lactamases (ESBLs) are enzymes that degrade
      beta-lactam antibiotics and have been reported to be an important cause of
      nosocomial infection in worldwide. METHODS: During 2009, 659 enterobacteria
      strains were isolated from different clinical specimens and tested for ESBL
      production. The disk approximation test, combined disk method and addition of
      clavulanic acid were used for phenotypic detection of the ESBL-producing strains
      and PCR for detection of the bla(TEM) and bla(CTX-M) genes. RESULTS: Among the
      isolates, 125 were ESBL producers. The bla(CTX-M) and bla(TEM) genes were
      detected in 90.4% and 75% of the strains, respectively. Most strains were
      isolated from urine. Klebsiella pneumoniae was the most prevalent organism.
      Microorganisms presented high resistance to the antibiotics. CONCLUSIONS: These
      results support the need for extending ESBL detection methods to different
      pathogens of the Enterobacteriaceae family because these methods are only
      currently standardized by the CLSI for Escherichia coli, Klebsiella pneumoniae,
      Klebsiella oxytoca and Proteus mirabilis. Carbapenems were the antibiotic class
      of choice for the treatment of infections caused by ESBL-producing
      Enterobacteriaceae.

PMID- 21860890
TI  - Differentiation between Candida albicans and Candida dubliniensis using
      hypertonic Sabouraud broth and tobacco agar.
AB  - INTRODUCTION: Opportunistic fungal infections in immunocompromised hosts are
      caused by Candida species, and the majority of such infections are due to Candida
      albicans. However, the emerging pathogen Candida dubliniensis demonstrates
      several phenotypic characteristics in common with C. albicans, such as production
      of germ tubes and chlamydospores, calling attention to the development of stable
      resistance to fluconazole in vitro. The aim of this study was to evaluate the
      performance of biochemistry identification in the differentiating between C.
      albicans and C. dubliniensis, by phenotyping of yeast identified as C. albicans.
      METHODS: Seventy-nine isolates identified as C. albicans by the API system ID 32C
      were grown on Sabouraud dextrose agar at 30 degrees C for 24-48h and then
      inoculated on hypertonic Sabouraud broth and tobacco agar. RESULTS: Our results
      showed that 17 (21.5%) isolates were growth-inhibited on hypertonic Sabouraud
      broth, a phenotypic trait inconsistent with C. albicans in this medium. However,
      the results observed on tobacco agar showed that only 9 (11.4%) of the growth
      inhibited isolates produced characteristic colonies of C. dubliniensis (rough
      colonies, yellowish-brown with abundant fragments of hyphae and chlamydospores).
      CONCLUSIONS: The results suggest that this method is a simple tool for screening
      C. albicans and non-albicans yeast and for verification of automated
      identification.

PMID- 21860891
TI  - Anti-Toxocara antibodies detected in children attending elementary school in
      Vitoria, State of Espirito Santo, Brazil: prevalence and associated factors.
AB  - INTRODUCTION: The aim of this study was to evaluate the frequency of anti
      Toxocara antibodies in serum from 7-year-old children attending elementary school
      in Vitoria-ES, Brazil and to correlate these antibodies with socio-demographic
      factors, the presence of intestinal helminths, blood eosinophil numbers, past
      history of allergy or asthma, and clinical manifestations of helminth infections.
      METHODS: The detection of anti-Toxocara antibodies was performed using an ELISA
      (Cellabs Pty Ltd)on serum from 391 children who had already been examined by
      fecal examination and blood cell counts. Data from clinical and physical
      examinations were obtained for all children. RESULTS: The prevalence of anti
      Toxocara antibodies was 51.6%, with no gender differences. No significant
      differences were observed between positive serology and the presence or absence
      of intestinal worms (60.3 and 51.7%, respectively; p = 0.286). The only variables
      significantly related to positive serology were onycophagy and the use of
      unfiltered water. Although eosinophilia (blood eosinophil count higher than
      600/mm3) was significantly related to the presence of a positive ELISA result,
      this significance disappeared when we considered only children without worms or
      without a past history of allergy or asthma. No clinical symptoms related to
      Toxocara infection were observed. CONCLUSIONS: There is a high prevalence of anti
      Toxocara antibodies in children attending elementary schools in Vitoria, which
      may be partially related to cross-reactivity with intestinal helminths or to a
      high frequency of infection with a small number of Toxocara eggs.

PMID- 21860892
TI  - [The AIDS epidemic in adolescents between the ages of 13 and 19 in the City of
      Rio de Janeiro, Brazil: space-time description].
AB  - INTRODUCTION: The purpose of this study was to analyze the dynamics of the AIDS
      epidemic affecting adolescents in Rio de Janeiro to establish healthy prevention
      strategies. The incidence of AIDS in Brazil is declining among men who have sex
      with men (MSM) except in individuals between 13 and 19 years of age, and the
      feminization phenomenon is more pronounced among adolescents. METHODS: We
      evaluated data from Sistema de Informacoes de Agravos de Notificacao (SINAN)
      regarding cases of AIDS in patients aged between 13 and 19 years through November
      2009. RESULTS: This study includes 656 cases. The incidence of AIDS increased
      until 1998, and, since 1996, more cases have been diagnosed in girls than in
      boys. The homo/bisexual exposure category predominantly consisted of boys
      (50.8%), and the heterosexual category predominantly consisted of girls (88.9%).
      The geographic distribution of the cases by year of diagnosis revealed that the
      increase was proportionally larger in the poorest area and that there was a large
      decrease in the wealthiest area. A decreasing linear tendency was observed in the
      relationship between the year of diagnosis and the human development index (HDI).
      CONCLUSIONS: This study demonstrates the need for greater investment in sexual
      health and reproductive services in the poorest areas of the city and in the
      promotion of healthy sexual practices directed to MSM and female adolescents.

PMID- 21860893
TI  - [Dengue: epidemiological aspects and the first outbreak in the Middle Solimoes
      Region of Coari in the State of Amazonas from 2008 to 2009].
AB  - INTRODUCTION: Dengue is one of the most prevalent infectious diseases in Brazil
      and is a major public health problem worldwide. It is most prevalent in tropical
      and subtropical regions with 2.5 to 3 billion people at risk of becoming
      infected. Thus, this study sought to demonstrate the epidemiological
      characteristics of individuals affected by dengue, its prevalence and its
      epidemic process in the Middle Solimoes region of Coari in the state of Amazonas
      between 2008 and 2009. METHODS: Epidemiological data were obtained through
      epidemiological monitoring by the Municipal Health Facility of the city of Coari,
      AM. The variables analyzed were the month of notification, the number of
      confirmed cases, the cases' genders, the cases' ages and their neighborhoods of
      residence. RESULTS: In total, 1,003 cases were reported (635 in 2008 and 368 in
      2009), and 639 cases were diagnosed as positive. Of these, +54% involved female
      subjects, and +46% were male. The majority of the affected individuals were
      between 10 and 49 years of age, and the spatial distribution was concentrated in
      neighborhoods near streams, lakes and areas in which housing had recently been
      disrupted. CONCLUSIONS: We concluded that, during the period studied, there was
      an outbreak of dengue in the City of Coari, AM. However, it is possible that a
      dengue epidemic may have occurred earlier in Coari without proper diagnosis or
      follow-up and that previously infected individuals may have traveled to the
      capital of Amazonas (Manaus), where the virus has circulated since 1998.

PMID- 21860894
TI  - [Geographical distribution of leptospirosis in Aracaju, State of Sergipe from
      2001 to 2007].
AB  - INTRODUCTION: Leptospirosis, a disease caused by pathogenic spirochetes of the
      genus Leptospira, is one of the most widespread zoonoses in the world and is
      considered an important public health problem. This paper aims to describe the
      spatial pattern of leptospirosis in the City of Aracaju from 2001 to 2007 in an
      effort to identify areas at risk for leptospirosis. METHODS: We used the ratio of
      Kernel, which represents the ratio between two surfaces, to visualize the surface
      of disease risk. The numerator corresponds to the number of cases geocoded to the
      census tract, and the denominator of the kernel corresponds to the population of
      these areas. Using this method, the areas with the highest density of cases were
      delineated and compared visually with socioeconomic factors, such as average
      income. RESULTS: The spatial pattern was different in periods of rain compared
      with periods of drought and did not coincide with the areas considered most at
      risk for the disease. This study revealed the importance of applying spatial
      analysis techniques in the field of public health. CONCLUSIONS: These findings
      indicate that the kernel is a useful tool for obtaining a comprehensive review of
      the epidemiology of leptospirosis in Aracaju, which supports the kernel's use by
      the municipal health departments and by the state.

PMID- 21860895
TI  - [Clinical and epidemiological profile of accidental tetanus cases in Ribeirao
      Preto in the State of Sao Paulo from 1990 to 2009].
AB  - INTRODUCTION: Tetanus remains a major health problem in developing countries. In
      Brazil, despite technological advances, no significant decrease in the lethality
      rate of tetanus have been documented in recent years. Clinical and
      epidemiological data from patients who were treated in Ribeirao Preto in the
      state of Sao Paulo, Brazil in the last two decades were analyzed in this case
      series. METHODS: Retrospective data regarding the demographics, clinical
      presentations and prognoses of patients admitted with clinical suspicion of
      tetanus to a tertiary referral university hospital from 1990 to 2009 were
      identified. The tetanus diagnosis was defined according to the Brazilian Ministry
      of Health criteria. RESULTS: Eleven cases out of 23 patients with suspected
      tetanus were included in this study (47.8% of positive cases). The Tetanus
      Severity Score ranged from 0 to 8 points. There were no deaths, but two (18.2%)
      patients had permanent neurological deficits. The median length of hospital stay
      was 17 days (6-98 days). The absence of deaths can be explained by early clinical
      diagnosis and prompt treatment. CONCLUSIONS: Ribeirao Preto is an area in which
      tetanus is not a severe public health problem.

PMID- 21860896
TI  - [Susceptibility of Culex quinquefasciatus larvae to different insecticides].
AB  - INTRODUCTION: This study aimed to assess the susceptibility of Culex
      quinquefasciatus larvae to two pyrethroids (Cypermethrin and Deltamethrin), two
      derivatives of Avermectin (Ivermectin and Abamectin) and an organophosphate
      (Temephos). METHODS: Third- and fourth-instar larvae of C. quinquefasciatus were
      exposed to different concentrations of insecticides (eleven repetitions)
      according to the World Health Organization's protocol. One hour after exposure,
      larvae were washed in dechlorinated tap water, transferred to plastic containers
      containing water without chlorine, fed and observed for periods of 24h until
      reaching adulthood. To determine lethal concentrations, the obtained values were
      submitted to regression analysis using the probit model with the Minitab 15
      program. RESULTS: The highest concentration used for the LC50 from probit
      analysis was for Temephos. The evaluated insecticides caused more pronounced
      larvae mortality in the first 24h with the exception of those exposed to
      ivermectin. CONCLUSIONS: This study demonstrates that larvae are susceptible to
      all tested insecticides and that there is a need for monitoring the use of
      insecticides.

PMID- 21860897
TI  - [Comparative biology and feeding behavior of Rhodnius neglectus and Rhodnius
      robustus (Triatominae) under laboratory conditions].
AB  - INTRODUCTION: The vector competence of triatomine insects is determined by
      studying their biology and feeding behavior under field and/or laboratory
      conditions. Factors including the number of bites, the amount of blood ingested
      and defecation time have implications for trypanosome transmission. The
      biological and behavioral parameters of Rhodnius neglectus and R. robustus were
      compared under experimental conditions to estimate differences in the potential
      transmission of trypanosomes. METHODS: The insects were observed daily to
      determine the period of nymphal development, mortality, detection of food source,
      number of bites, time of blood meal intake, amount of blood ingested, time
      elapsed between the end of the meal and the first defecation and the frequency of
      defecation. RESULTS: Although the nymphal development of R. neglectus (156.4 +/-
      25.05d) was lower than that of R. robustus (204.7 +/- 13.22d), the mortality
      between species was similar (63.8 and 65% respectively).R. robustus and R.
      neglectus quickly located the food source, especially in the first instar (2.5
      and 1.6 min, respectively). Although the time of blood meal intake was similar
      between the species, R. robustus ingested a larger amount of blood on average at
      all stages and exhibited higher values for the fifth instar. Nymphs of R.
      neglectus bit more frequently, and they defecated faster and more often than
      those of R. robustus. CONCLUSIONS: Under laboratory conditions, R. neglectus has
      a greater potential for transmission of Trypanosoma cruzi and T. rangeli than
      does R. robustus, an attribute that should be further evaluated in experimental
      infections.

PMID- 21860898
TI  - [The presence of Culicidae species in medium-sized cities in the State of Sao
      Paulo, Brazil and the risk of West Nile fever and other arbovirus infection].
AB  - INTRODUCTION: The objectives for this study were to measure the diversity of
      Culicidae species, describe their abundance and seasonal variation in Sao Jose do
      Rio Preto, SP, and discuss the risk of arbovirus infections. METHODS: The
      collection of larval and adult mosquitoes was conducted monthly from 2006 to 2007
      in an urban area and four sections of forested land. In the urban area, larvae
      were collected from sites where oviposition by Culex mosquitoes was most likely
      to occur. At two of the four sites in the forested land, adult mosquitoes were
      collected with the use of CDC traps at night, and a Nasci aspirator was used in
      the daytime at the two other collection sites. RESULTS: In the urban area, 34
      Culicidae species were identified out of a total sample of 8,683 specimens; of
      these specimens, 80.7% were Culex quinquefasciatus, 9.6% were Culex coronator,
      3.2% were Aedes albopictus, and 1.1% were Ochlerotatus fluviatilis. The abundance
      of Cx. quinquefasciatus larvae was negatively related to rainfal. In the woods,
      2,268 mosquitoes were collected, representing 10 genera and 46 species. The most
      abundant mosquito species were Aedeomyia squamipennis, Culex coronator, Culex
      (Mel.) Melanoconion section, Culex declarator, Ochlerotatus scapularis, Anopheles
      triannulatus, Culex bidens/interfor and Culex habilitator/pseudojhantinosoma.
      CONCLUSIONS: The abundance of Cx. quinquefasciatus in the urban area and the
      presence of other Culicidae species in urban areas and forested land point to the
      possibility of the transmission of West Nile virus and other arbovirus infections
      in Sao Jose do Rio Preto and other cities. Thus, the enacting of measures aimed
      at the surveillance of these arbovirus infections is essential.

PMID- 21860899
TI  - [The presence of mosquitoes (Diptera: Culicidae) in flood containment reservoirs
      in the eastern region of the City of Sao Paulo, Brazil].
AB  - INTRODUCTION: Alterations in the environment contribute to changes in weather
      patterns, which cause an increase in rainfall, which causes flooding. Flooding
      has been addressed by building reservoirs, called piscinoes, to contain the
      excess rain. In this report, we evaluated the Culicidae fauna of epidemiological
      importance in the reservoirs of Caguacu and Inhumas. METHODS: Monthly collections
      were performed in both reservoirs, which are situated in the Eastern section of
      the City of Sao Paulo. Monthly collections of Culicidae were undertaken using the
      entomological scoop method and a battery aspirator during the period between
      March 2006 and February 2007. Descriptive statistical and simple linear
      regression analyses of the data were carried out. RESULTS: A total of 8,917
      Culicidae mosquitoes were collected. The majority of the insects captured were of
      Culex (Culex) quinquefasciatus, representing 98.9% of the specimens identified in
      the Inhumas and 95.2% of those identified in Caguacu. In the Caguacu reservoir,
      the greatest frequency of immature mosquitoes was observed in the spillway (61%).
      In the Inhumas reservoir, the greatest occurrence of immature Culicidae was
      detected in the channel (42.6%). The linear regression analysis showed that 87%
      of the larvae in the third and fourth stages and 60% of the pupae were collected
      during periods of rainfall. In the Inhumas reservoir, 36% of the larvae and 18%
      of the pupae were collected during periods of rainfall. CONCLUSIONS: Culex
      quinquefasciatus, a vector for agents of filariasis and arbovirus diseases and a
      nuisance to the human population, was frequent in both environments. Methods of
      control of the species in the studied dams are necessary to reduce their
      epidemiological potential.

PMID- 21860900
TI  - Giardia duodenalis: genotypic comparison between a human and a canine isolates.
AB  - INTRODUCTION: Evidence suggests that giardiasis is a zoonotic disease. The
      present work aimed to evaluate the genetic identity of Giardia duodenalis
      isolated from human and dog fecal samples from Belo Horizonte. METHODS: Human and
      dog fecal samples were cultured for isolation of G. duodenalis. To determine the
      genotype of the isolates, primers that amplify a specific region in rRNA of the
      protozoan were used. RESULTS: Two G. duodenalis isolates were obtained, which
      belong to the subgroup A genotype. CONCLUSIONS: These findings suggest that the
      transmission of giardiasis follows a zoonotic pattern.

PMID- 21860901
TI  - First report of Eratyrus mucronatus, Stal, 1859, (Hemiptera, Reduviidae,
      Triatominae), in the State of Rondonia, Brazil.
AB  - INTRODUCTION: This paper reports, for the first time, the presence of the
      Eratyrus mucronatus species in the State of Rondonia, Brazil. METHODS: These
      specimens were caught by chance in the forest and later they were collected using
      luminous traps. RESULTS: After finding these specimens, the number of the
      Triatominae genera in Rondonia rose to four, while its species rose to seven.
      CONCLUSIONS: Complimentary studies will be conducted in order to allow for
      clearer understanding the ecology of this arthropod, its possible role in
      transmitting Chagas' disease and its current geographical distribution.

PMID- 21860902
TI  - [Prevalence and epidemiological aspects of intestinal parasites in elderly of
      Parnaiba, State of Piaui].
AB  - INTRODUCTION: Since intestinal parasites pose public health problems, this work
      aimed to determine certain epidemiological aspects of these pathologies in
      elderly individuals from Parnaiba. METHODS: Using the method of Hoffman, 294
      fecal samples from individuals 65 years-old or over were analyzed. Each
      participant responded to a questionnaire used for description analysis of the
      population. RESULTS: The prevalence of intestinal parasites was 40.5%. The
      questionnaires showed alarming results regarding the noxious conditions in which
      this population is inserted. CONCLUSIONS: High prevalence of intestinal parasites
      exists among the elderly population of Parnaiba, indicating an epidemiological
      state of some concern.

PMID- 21860903
TI  - [Prevalence and risk factors of human infection by Toxocara canis in Salvador,
      State of Bahia, Brazil].
AB  - INTRODUCTION: Larva migrans visceral is caused by Toxocara sp and has never been
      studied in Bahia. This work investigated the prevalence and risk factors for
      infection by Toxocara canis in individuals from Salvador, State of Bahia.
      METHODS: Three hundred and thirty-eight individuals were investigated for the
      presence of serum IgG anti-T. canis. RESULTS: IgG anti-T. canis was higher in
      individuals from lower social classes who had more contact with dogs and cats,
      indicating that these variables are factors risk for this infection. CONCLUSIONS:
      The prevalence of T. canis infection was high. The risk factors for this
      infection identified are in agreement with in the literature.

PMID- 21860904
TI  - Immunophenotyping of circulating T cells in a mucosal leishmaniasis patient
      coinfected with HIV.
AB  - HIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2
      pattern of cytokine production. However, little information is available
      regarding the lymphocytic response in untreated coinfected patients. This work
      presents the immunophenotyping of Leishmania-stimulated T cells from a treatment
      naIve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69
      expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular
      staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL
      17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17
      population may serve as parasitic evasion mechanisms in HIV/ML. Further studies
      are required to confirm these results.

PMID- 21860905
TI  - Human herpesvirus 6: report of emerging pathogen in five patients with HIV/AIDS
      and review of the literature.
AB  - The reactivation of human herpesvirus 6 (HHV-6) in patients with AIDS can result
      in an acute and severe diffuse meningoencephalitis. We describe the
      epidemiological, clinical and outcome findings of five patients with diagnosis of
      HIV/AIDS and central nervous system involvement (CNS) due to HHV-6. Fever was
      present in all the patients. Meningeal compromise, seizures and encephalitis were
      present in some of the patients. Polymerase chain reaction (PCR) of cerebrospinal
      fluid (CSF) specimens was positive for HHV-6 in all the patients. HHV-6 should be
      included among opportunistic and emerging pathogens that involve the CNS in
      patients with AIDS.

PMID- 21860906
TI  - Rabies virus in Molossus molossus (Chiroptera: Molossidae) in the State of
      Pernambuco, Northeastern Brazil.
AB  - Rabies virus was detected in bats (Molossus molossus) from an urban area in the
      City of Recife, State of Pernambuco, Brazil. Four individuals were found during
      the day in visible, non-habitual places, lying on the ground, but still alive. No
      contact occurred with people or animals. Of these, only two were identified; it
      was not possible to identify two specimens, since they were incinerated prior to
      identification. Diagnosis was positive by direct immunofluorescence and
      intracerebral inoculation in mice. This study presents the first instance in
      which the virus was detected in insectivorous bats in the State of Pernambuco.

PMID- 21860907
TI  - Notification of the first isolation of Cacipacore virus in a human in the State
      of Rondonia, Brazil.
AB  - Flavivirus is a genus of arthropod-transmitted viruses of the family
      Flaviviridae, and in Brazil, up to eleven different Flavivirus have been
      isolated. We collected blood from farmers in the municipality of Theobroma, which
      is located 320km from the City of Porto Velho, the former capital of the
      Brazilian State of Rondonia. For viral isolation, we used newborn mouse brain,
      followed by RT-PCR with specific universal Flavivirus primers. We obtained
      fragments 958bp and 800bp in length. Based on BLAST, these sequences were 91%
      similar to a sequence of Cacipacore virus.

PMID- 21860908
TI  - Henoch-Schonlein purpura following influenza A H1N1 vaccination.

PMID- 21860909
TI  - Joaquim Romeu Cancado (1913-2011).

PMID- 21860910
TI  - Daily oviposition activity of Aedes aegypti in Oran, Argentina.
AB  - The study aimed to determinate the maximum daily peak of Aedes aegypti
      oviposition in the city of Oran, northwestern Argentina. Biweekly samplings were
      taken between November 2006 and February 2007 (spring-summer). The city was
      divided into three areas (north, center, and south) and households were randomly
      selected. Two ovitraps were placed outdoors in the selected houses. Ovitraps were
      replaced every four hours, from morning (8 a.m.) to late afternoon (8 p.m.). The
      largest number of eggs was recorded between 4 p.m. and 8 p.m. (81%). These
      findings enhance our understanding of the vector and thus its control such as
      spraying during the hours of peak oviposition activity.

PMID- 21860911
TI  - Association between alcohol abuse during pregnancy and birth weight.
AB  - OBJECTIVE: To assess the association between alcohol abuse during gestation and
      low birth weight. METHODS: Cross-sectional, population-based nested study from a
      cohort of 957 pregnant women who received prenatal assistance through Sistema
      Unico de Saude (National Health System) in the city of Pelotas, Southern Brazil,
      and delivered their babies between September 2007 and September 2008. The mothers
      were interviewed at two distinct moments: prenatal and postpartum periods. In
      order to verify alcohol abuse, the CAGE (Cut down, Annoyed by criticism, Guilty
      and Eye-opener) scale was used. Bivariate analyses were carried out, as well as
      multiple logistic regression adjusted by the variables prematurity and alcohol
      abuse. The level of significance that was adopted was 95%. RESULTS: Of the women
      who participated in the study, 2.1% abused alcohol during pregnancy and, among
      these, 26.3% had low birth weight children. There was an association between
      alcohol abuse and low birth weight (p<0.038). CONCLUSIONS: The findings indicate
      that alcohol abuse during pregnancy is associated with low birth weight.

PMID- 21860913
TI  - SISPRENATAL as a tool for evaluating quality of prenatal care.
AB  - OBJECTIVE: To evaluate coverage by the Prenatal and Birth Humanization Program,
      according to its minimal requirements and process indicators, by comparing
      information from prenatal booklets to SISPRENATAL (System to Accompany the
      Prenatal and Birth Humanization Program). METHODS: A cross-sectional study was
      carried out with prenatal data from 1,489 women in the postpartum period after
      birth in the Brazilian Unified Health System, between November 2008 to October
      2009 in Sao Carlos municipality, Southeastern Brazil. Data were collected from
      the prenatal booklet and afterwards from the SISPRENATAL. Information from both
      sources was compared using the McNemar Chi2 test for related samples. RESULTS:
      Prenatal coverage in relation to the number of live births was 97.1% according to
      the prenatal booklet and 92.8% according to SISPRENATAL. There were statistical
      significant differences between both sources of information for all the minimum
      requirements of the Prenatal and Birth Humanization Program, and also the process
      indicators. Except for the first prenatal visit, the prenatal booklet always had
      greater frequencies than SISPRENATAL. The proportion of women with six or more
      prenatal visits and all basic exams was 72.5%, according to the prenatal booklet
      and 39.4% by the official system. These differences remained for the five health
      regions in the municipality. CONCLUSIONS: SISPRENATAL was not a reliable source
      for evaluating the available information on care during pregnancy. There was high
      adherence to the Prenatal and Birth Humanization Program, but documentation of
      information was insufficient for all the minimum requirements and process
      indicators. Ten years after the start of the program, municipalities should
      provide adequate quality of care and build health professional capacity for
      proper documentation of health information.

PMID- 21860912
TI  - Sensitivity and specificity in the diagnosis of hypertension with different
      methods.
AB  - OBJECTIVE: To evaluate sensitivity and specificity of different protocols for
      blood pressure measurement for the diagnosis of hypertension in adults. METHODS:
      Cross-sectional study conducted in a non-probabilistic sample of 250 public
      servants of both sexes aged 35 to 74 years in Vitoria, southeastern Brazil,
      between 2008 and 2010. The participants had their blood pressure measured using
      three different methods: clinic measurement, self-measured and 24-hour ambulatory
      measurement. They were all interviewed to obtain sociodemographic information and
      had their anthropometric data (weight, height, waist circumference) collected.
      Clinic measurement and self-measured were analyzed against the gold standard
      ambulatory measurement. Measures of diagnostic performance (sensitivity,
      specificity, accuracy and positive and negative predictive values) were
      calculated. The Bland & Altman method was used to evaluate agreement between
      ambulatory measurement (standard deviation for daytime measurements) and self
      measured (standard deviation of four measurements). A 5% significance level was
      used for all analyses. RESULTS: Self-measured blood pressure showed higher
      sensitivity (S=84%, 95%CI 75;93) and overall accuracy (0.817, p<0.001) in the
      diagnosis of hypertension than clinic measurement (S=79%, 95%CI 73;86, and
      overall accuracy=0.815, p<0.001). Despite the strong correlation with daytime
      ambulatory measurement values (r=0.843, p<0.001), self-measured values did not
      show good agreement with daytime systolic ambulatory values (bias=5.82, 95%CI
      4.49;7.15). Seven (2.8%) cases of white coat hypertension, 26 (10.4%) of masked
      hypertension and 46 (18.4%) of white-coat effect were identified. CONCLUSIONS:
      The study shows that self-measured blood pressure has higher sensitivity than
      clinic measurement to identify true hypertension. The negative predictive values
      found confirm the superiority of self-measured when compared to clinic in
      identifying truly normotensive individuals. However, clinic measurement cannot be
      replaced with self-measured, as it is still the most reliable method for the
      diagnosis of hypertension.

PMID- 21860914
TI  - Challenges faced by the stricto sensu graduate programs.

PMID- 21860915
TI  - Microtensile bond strength of quartz fiber posts to different composite cores.
AB  - The aim of this in vitro study was to assess the microtensile bond strength of
      quartz fiber posts to different composites, and to composite combinations used as
      core materials. Thirty fiber posts were treated with a 24% hydrogen peroxide
      solution and silanized. The posts were divided into 5 groups according to the
      resin composite used as follows (n = 6): G1 - AElite Flow (Bisco, Inc), G2 -
      Filtek Z250 (3M ESPE), G3 - Biscore (Bisco, Inc), G4 - AElite Flow + Filtek Z250,
      G5 - AElite Flow + Biscore. The resin composites were placed around the posts to
      produce cylindrical specimens. Two 1-mm2 thick sticks containing the post in the
      center and composite cores on both ends were provided from each cylinder and
      tested for microtensile strength with a crosshead speed of 0.5 mm/min. One-way
      ANOVA and Tukey HSD tests were used for statistical analysis. Fractured surfaces
      were observed using a stereomicroscope with 20* magnification. Scanning electron
      microscopy (SEM) was used to evaluate the interface of the fractured sticks. The
      results showed that G2 had the highest bond strength values, and the lowest
      values were seen with G3. There were significant differences between groups 1, 2,
      4 and groups 3, 5 (p < 0.05). Under the stereomicroscope, most of the failures
      were adhesive between the post and core material. Under SEM, AElite and Z250 had
      smoother surfaces than Biscore, containing less porosities and voids.

PMID- 21860916
TI  - Photoelastic analysis of stress generated by a silorane-based restoration system.
AB  - Silorane-based composite, an epoxy material, was marketed as promising less
      polymerization contraction than conventional restorative materials. The aim of
      this study was to evaluate, by means of photoelasticity, the polymerization
      stress generated by a silorane-based composite. Thirty photoelastic rings with
      orifices measuring 5 mm (d) * 3 mm (h) were prepared and divided into 6 groups (n
      = 5) according to the material tested. The inside walls of the rings were
      sandblasted with aluminum oxide, after which the restorative materials were
      inserted into the orifices and photoactivated according to the manufacturer's
      instructions. The specimens were analyzed and the visual representation of the
      stress was measured considering the isochromatic ring of first order. The data
      were converted to MPa and subjected to ANOVA and Tukey's test (alpha= 0.05). The
      adhesive Filtek P-90 (G5) showed high contraction stress (p < 0.05) when compared
      to G1, G2, G3, G4, and G6, which did not differ from each other (p > 0.05). The
      composite Filtek P-90 showed similar contraction stress compared to the
      conventional composite and, additionally, its adhesive showed higher stress than
      did the etch-and-rinse 2-step adhesive.

PMID- 21860917
TI  - Dentists' level of knowledge of the treatment plans for periodontal ligament
      injuries after dentoalveolar trauma.
AB  - This study investigated the level of knowledge held by dentists about the
      possible treatment plan procedures for periodontal ligament injuries after
      dentoalveolar trauma. A 5-item self-applied questionnaire was prepared with
      questions referring to the professional profile of the interviewees and to the
      treatment plan they would propose for periodontal ligament injuries secondary to
      dentoalveolar trauma. The questionnaires were filled out by 693 dentists
      attending the 23rd Annual Meeting of the Brazilian Society for Dental Research,
      and the data obtained were subjected to descriptive analysis. Either the chi
      square test or Fisher's exact test was applied to assess associations among
      variables, at a 5% level of significance. The results revealed that dentists
      experienced difficulty in establishing a treatment plan for subluxation, and for
      extrusive, lateral and intrusive luxations. In general, holding a dental
      specialty degree had no influence on the knowledge about treatment plan
      procedures for the most severe injuries. It could be concluded that the dentists
      participating in this study, whether specialists or not, did not have sufficient
      knowledge to treat most of the periodontal ligament injuries resulting from
      dentoalveolar trauma adequately.

PMID- 21860918
TI  - Influence of Hero Apical instruments on cleaning ovoid-shaped root canals.
AB  - The cleaning capacity of Hero 642 nickel-titanium files, complemented by the Hero
      Apical instruments in flattened roots, was determined by histological analysis,
      considering the area of action of the instruments on the coronal walls and the
      presence of remaining debris. Twenty-four single-canal, human mandibular incisors
      were divided into three groups and prepared as follows: GI, instrumented with
      Hero 642 NiTi files 30/.06, 25/.06, 20/.06, 25/.06, and 30/.06; GII, instrumented
      as GI followed by Hero Apical size 30/.06; GIII, instrumented as GI followed by
      Hero Apical sizes 30/.06 and 30/.08, then returning to 30/.06 with pendulum
      movements. The apical thirds were prepared for histological processing, analyzed
      at 40* magnification and the images were examined morphometrically. Statistical
      analysis showed that GIII presented the best results for removing debris (5.22%
      +/- 4.13), with more contact between the instruments and the root canal walls
      (19.31% +/- 0.15). This differed statistically from GI (14.04% +/- 4.96 debris
      removal, with 42.96% +/- 7.11 instrument contact) and GII (12.62% +/- 5.76 debris
      removal, with 35.01% +/- 0.15 instrument contact). Root canal preparation with
      Hero 642, complemented by Hero Apical instruments (30/.06 and 30/.08, then re
      instrumented with Hero Apical 30/.06 using pendulum movements), was more
      efficient for debris removal and allowed more contact of the instruments with the
      root canal walls. GII presented the worst results.

PMID- 21860919
TI  - Dental trauma in individuals with severe cerebral palsy: prevalence and
      associated factors.
AB  - The aim of the present study was to determine the prevalence of dental trauma and
      associated factors among a sample of patients with severe cerebral palsy. The
      sample was made up of 120 individuals equally divided into two groups. The group
      with cerebral palsy was made up of 60 patients diagnosed with the spastic form of
      the disease. The control group was made up of 60 individuals with no mental
      impairment. Questionnaires were used to collect information on individual,
      socioeconomic and behavioral characteristics. Dental trauma was assessed based on
      the clinical chart of each participant, on a questionnaire and on a clinical
      evaluation to determine past injuries. Mouth mirrors and millimeter periodontal
      probes (Community Periodontal Index probe) were used to measure overjet. Lip seal
      and breathing type were determined during the clinical exams and interviews.
      Statistical analysis involved the chi-square test (p < 0.05) and multivariate
      logistic regression (forward stepwise procedure). The prevalence of dental trauma
      was greater among individuals with cerebral palsy (18%) than in the control group
      (5%), with the difference achieving statistical significance (p = 0.023).
      Individuals with lip incompetence had a greater chance of exhibiting dental
      trauma (OR [CI 95%] = 3.81 [1.19-12.24]). The prevalence of dental trauma among
      individuals with cerebral palsy was high. A lack of lip seal was identified as a
      factor directly associated to this prevalence.

PMID- 21860920
TI  - Crown dimensions and proximal enamel thickness of mandibular second bicuspids.
AB  - To achieve proper recontouring of anterior and posterior teeth, to obtain optimal
      morphology during enamel stripping, it is important to be aware of dental
      anatomy. This study aimed at evaluating crown dimensions and proximal enamel
      thickness in a sample of 40 extracted sound, human, mandibular, second bicuspids
      (20 right and 20 left). Mesiodistal, cervico-occlusal and buccolingual crown
      dimensions were measured using a digital caliper, accurate to 0.01 mm. Teeth were
      embedded in acrylic resin and cut along their long axes through the proximal
      surfaces to obtain 0.7 mm-thick central sections. Enamel thickness on the cut
      sections was measured using a perfilometer. Comparative analyses were carried out
      using the Student's-t test (alpha= 5%). The mean mesiodistal crown widths for
      right and left teeth were 7.79 mm (+/- 0.47) and 7.70 mm (+/- 0.51),
      respectively. Mean cervico-occlusal heights ranged from 8.31 mm (+/- 0.75) on the
      right to 8.38 mm (+/- 0.85) on the left teeth. The mean values for the
      buccolingual dimension were 8.67 mm (+/- 0.70) on the right and 8.65 mm (+/-
      0.54) on the left teeth. The mean enamel thickness on the mesial surfaces ranged
      from 1.35 mm (+/- 0.22) to 1.40 mm (+/- 0.17), on the left and right sides,
      respectively. On the distal surfaces, the corresponding values were 1.44 mm (+/-
      0.21) and 1.46 mm (+/- 0.12). No significant differences were found between
      measurements for right and left teeth. However, enamel thickness was
      significantly greater on the distal surfaces, compared with the mesial surfaces.

PMID- 21860921
TI  - Bottle feeding, increased overjet and Class 2 primary canine relationship: is
      there any association?
AB  - The aim of this study was to investigate the association between bottle feeding
      and prevalence rates of increased overjet and Class 2 primary canine
      relationship. The sample consisted of 911 children (461 boys, 450 girls) aged 3
      (13.9%), 4 (40.8%), 5 (34%) and 6 (11.3%) years, with complete primary dentition.
      Information about nutritive and nonnutritive (pacifier and/or digit) sucking
      habits was collected through questionnaires. Three calibrated dentists (kappa:
      0.9-1.0 and Rs > 0.90) performed the clinical assessments. The children were
      divided into four groups: G1 - not bottle-fed; G2 - exclusively bottle-fed; G3 -
      breast- and bottle-fed, bottle feeding ceased before 3 years of age; and G4 -
      breast- and bottle-fed, bottle feeding ceased between 3 and 4 years of age.
      Associations between nutritive and nonnutritive sucking behaviors and the
      malocclusions studied were analyzed by multiple binary logistic regression
      (alpha= 0.05). The frequencies of increased overjet were: 25.3% (G1), 38.8% (G2),
      39.2% (G3) and 47.8% (G4). The percentages of Class 2 canine relationship were:
      27.9% (G1), 48.8% (G2), 43.4% (G3) and 43% (G4). No significant effect of bottle
      feeding was found. The chances of diagnosing increased overjet (O.R. = 4.42, p <
      0.001) and Class 2 canine relationship (O.R. = 4.02, p < 0.001) were greater for
      children with pacifier and/or digit-sucking habits, compared to those without a
      history of nonnutritive sucking behavior. It may be suggested that bottle feeding
      alone is not directly associated with higher prevalence rates of increased
      overjet and Class 2 canine relationship in the primary dentition.

PMID- 21860922
TI  - Comparative efficacy of two daily use mouthrinses: randomized clinical trial
      using an experimental gingivitis model.
AB  - Two antimicrobial agents, a fixed combination of essential oils (EOs) and 0.07%
      cetylpyridinium chloride (CPC) are found in commercially available mouthrinses,
      Listerine(r) Antiseptic and Crest(r) Pro HealthTM, respectively. Both mouthrinses
      have been shown to control dental plaque and gingivitis in short and longer term
      studies. The aim of this study was to determine the comparative effectiveness of
      these two mouthrinses using a 2-week experimental gingivitis model. Qualified
      subjects were randomly assigned to one of three mouthrinse groups: a fixed
      combination of EOs, 0.07% CPC, or negative control (C) rinse. Following baseline
      clinical assessments and a dental prophylaxis, subjects began a two-week period
      in which they rinsed twice daily with their assigned rinse and abstained from any
      mechanical oral hygiene procedures or other oral care products. Subjects were
      reassessed at the end of the two-week period. One hundred and forty-seven
      subjects were randomized and 142 completed this study. After two weeks use, the
      EOs rinse was superior (p < 0.011) to the CPC rinse in inhibiting the development
      of gingivitis, plaque, and bleeding, with 9.4% and 6.6% reductions compared to
      CPC for gingivitis and plaque, respectively. Both rinses were superior to the
      negative control rinse (p < 0.001). This study demonstrates that the essential
      oil-containing mouthrinse has superior antiplaque/antigingivitis effectiveness
      compared to the 0.07% CPC-containing mouthrinse without mechanical oral hygiene
      influence.

PMID- 21860923
TI  - Influence of remaining coronal structure and finish line on the fracture strength
      of roots restored with metallic posts.
AB  - The purpose of this study was to evaluate the fracture strength of roots that
      were prosthetically restored with metallic posts with or without any remaining
      coronal structure and with different finish lines. Sixty bovine incisors were
      sectioned below the cementoenamel junction, endodontically treated, and randomly
      divided into six experimental groups (n = 10) containing teeth with or without
      any remaining coronal structure, and with a beveled shoulder, a bevel, or a
      shoulder finish line design. The metallic posts were luted with dual-cured resin
      cement. The cores were made with composite resin, and metal crowns were cemented
      with zinc phosphate cement. The specimens were subjected to a tangential
      compressive load (135o angle) at a crosshead speed of 0.5 mm/min until failure,
      using a universal testing machine. The fracture strength data were analyzed using
      the ANOVA and LSMeans (least square means) tests (alpha= 0.05). The data
      indicated that the teeth with 2 mm of remaining coronal structure showed the
      highest fracture strength values when compared with the teeth without any
      remaining structure (p < 0.05). As to the different finish line designs, the
      highest fracture strength values were obtained for the beveled shoulder, followed
      by the bevel and then by the shoulder designs (p < 0.05). It may be concluded
      that, to increase fracture strength, a beveled shoulder and 2 mm of remaining
      coronal structure are the ideal conditions.

PMID- 21860924
TI  - Comparison between cone-beam and multislice computed tomography for
      identification of simulated bone lesions.
AB  - There are many studies that compare the accuracy of multislice (MSCT) and cone
      beam (CBCT) computed tomography for evaluations in the maxillofacial region.
      However, further studies comparing both acquisition techniques for the evaluation
      of simulated mandibular bone lesions are needed. The aim of this study was to
      compare the accuracy of MSCT and CBCT in the diagnosis of simulated mandibular
      bone lesions by means of cross sectional images and axial/MPR slices. Lesions
      with different dimensions, shape and locularity were produced in 15 dry
      mandibles. The images were obtained following the cross sectional and axial/MPR
      (Multiplanar Reconstruction) imaging protocols and were interpreted
      independently. CBCT and MSCT showed similar results in depicting the percentage
      of cortical bone involvement, with great sensitivity and specificity (p < 0.005).
      There were no significant intra- or inter-examiner differences between axial/MPR
      images and cross sectional images with regard to sensitivity and specificity.
      CBCT showed results similar to those of MSCT for the identification of the number
      of simulated bone lesions. Cross sectional slices and axial/MPR images presented
      high accuracy, proving useful for bone lesion diagnosis.

PMID- 21860925
TI  - Interaction between staining and degradation of a composite resin in contact with
      colored foods.
AB  - Composite resins might be susceptible to degradation and staining when in contact
      with some foods and drinks. This study evaluated color alteration and changes in
      microhardness of a microhybrid composite after immersion in different colored
      foods and determined whether there was a correlation between these two variables.
      Eighty composite disks were randomly divided into 8 experimental groups (n = 10):
      kept dry; deionized water; orange juice; passion fruit juice; grape juice;
      ketchup; mustard and soy sauce. The disks were individually immersed in their
      respective test substance at 37 oC, for a period of 28 days. Superficial analysis
      of the disk specimens was performed by taking microhardness measurements
      (Vickers, 50 g load for 45 seconds) and color alterations were determined with a
      spectrophotometer (CINTRA 10- using a CIEL*a*b* system, 400-700 nm wavelength,
      illuminant d65 and standard observer of 2o) at the following times: baseline
      (before immersion), 1, 7, 14, 21 and 28 days. Results were analyzed by ANOVA and
      Tukey's test (p < 0.05). Both variables were also submitted to Pearson's
      correlation test (p < 0.05). The passion fruit group underwent the greatest
      microhardness change, while the mustard group suffered the greatest color
      alteration. Significant positive correlation was found between the two variables
      for the groups deionized water, grape juice, soy sauce and ketchup. Not all color
      alteration could be associated with surface degradation.

PMID- 21860926
TI  - [Gestational diabetes and urinary incontinence: the interaction of gynecology and
      obstetrics].

PMID- 21860927
TI  - [Conjoined twins: prenatal diagnosis, delivery and postnatal outcome].
AB  - PURPOSE: The aim of this study was to analyze conjoined twins in terms of
      antenatal, delivery and postnatal aspects. METHODS: A retrospective descriptive
      analysis of prenatally diagnosed conjoined twins. Prenatal ultrasound and
      echocardiography, delivery details, postnatal follow-up, surgical separation and
      post mortem data were reviewed. The twins were classified according to the type
      of fusion between fetal structures. The following data were analyzed: ultrasound
      and echocardiographic findings, antenatal lethality and possibility of surgical
      separation, delivery details and survival rates. RESULTS: Forty cases of
      conjoined twins were included in the study. There were 72.5% cases of
      thoracophagus, 12.5% of paraphagus, 7.5% of omphalo-ischiophagus, 5.0% of
      omphalophagus, and 2.5% of cephalophagus. Judicial termination of pregnancy was
      requested in 58.8% of the cases. Cesarean section was performed in all cases in
      which pregnancy was not terminated. The mean gestational age at delivery was 35
      weeks; all twins were live births with a mean birth weight of 3,860 g and 88%
      died postnatally. Ten percent of the live borns were submitted to surgical
      separation with a 60% survival rate. The total survival rate was 7.5% and
      postnatal survival was 12%. Antenatal evaluation of lethality and possibility of
      surgical separation were precise. There were no maternal complications related to
      delivery. CONCLUSION: Conjoined twins present a dismal prognosis mainly related
      to the complex cardiac fusion present in the majority of cases with thoracic
      sharing. At referring centers, prenatal ultrasound and echocardiographic
      evaluation accurately delineate fetal prognosis and the possibility of postnatal
      surgical separation.

PMID- 21860928
TI  - [Pregnancy and gestational diabetes: a prejudicial combination to female sexual
      function?].
AB  - PURPOSE: To compare the sexual function of healthy adult pregnant women with that
      of gestational diabetes patients (GDM) in the third trimester. METHODS: This
      cross-sectional study enrolled two groups of women managed antenatal care
      clinics. Inclusion criteria were: maternal age .20 years, gestational age at
      least 28 weeks, being in a heterosexual relationship with the same partner for at
      least 6 months, and being able to read. We excluded women with a medical
      recommendation for sexual abstinence due to clinical or obstetric disorders;
      hypertension controlled through medications; pregnancy resulting from rape;
      absent or sexually unavailable partner in the last month; hospital admission in
      the last month; use of vaginal creams in the last 30 days; multiple pregnancy,
      regular use of alcohol or illicit drugs or use of medications that can interfere
      with sexual function. Eighty-seven patients fulfilled the selection criteria and
      were included in the study. The Sexual Quotient . Feminine Version (QS-F)
      questionnaire was used to assess sexual function. Student's t and chi2 tests were
      used to compare differences between groups and p<0.05 was considered significant.
      RESULTS: The mean gestational age of the participants was 34 weeks. There were no
      significant differences in the mean QS-F scores between groups (62.5 healthy vs
      62.8 GDM women, p=0.9). Approximately half the participants (47 and 47.5% of the
      healthy and GDM women, respectively, p=0.9) had total scores up to 60, indicative
      of dysfunction in one of the assessed domains (desire, sexual satisfaction,
      arousal, orgasm, dyspareunia and vaginismus). CONCLUSIONS: The prevalence of
      sexual dysfunction was high among women in the third trimester of pregnancy and
      did not differ significantly between healthy women and women with GDM.

PMID- 21860929
TI  - [Effects of daily administration of a stavudine/nelfinavir association on the
      fetuses and placentas of female albino rats].
AB  - PURPOSE: To evaluate the effect of administration of a stavudine/nelfinavir
      combination on the rat pregnancy by assessing maternal and concepts weights, as
      well as the number of implantations, fetuses, placentas, resorptions and maternal
      and fetal mortality. METHODS: Forty adult pregnant Wistar rats of the EPM-1
      strain were randomly divided into four groups: control (GCtrl--drug vehicle
      control, n=10), and three experimental groups, which were treated with an oral
      solution of stavudine/nelfinavir (ExpI--1/40 mg/kg b.w., n=10; ExpII--3/120 mg/kg
      b.w., n=10; ExpIII--9/360 mg/kg b.w., n=10) from day 0 to the 20th day of
      pregnancy. Maternal body weights were determined at the start of the experiment
      and on the 7th, 14th and the 20th day thereafter. At term (20th day) the rats
      were anesthetized and, upon laparotomy and hysterotomy, the number of
      implantations, resorptions, living fetuses, placentae and intrauterine deaths
      were recorded. The collected fetuses and placentae were weighed and the concepts
      were examined under a stereomicroscope for possible external malformations.
      Statistical analysis was performed by analysis of variance (ANOVA) complemented
      by the Kruskal-Wallis test (p<0.05). RESULTS: There was a progressive and gradual
      increase in body weight during the course of pregnancy in all groups, which was
      more evident in the final period, but with no significant difference between
      groups. The mean number of fetuses, placentas, implantations, and fetal and
      placental weights showed no significant differences between groups. Also, no
      resorptions or external malformations were found in the experimental groups.
      However, between the 8th and 14th days of gestation, there was one case of
      maternal mortality in each experimental group. CONCLUSIONS: The administration of
      a stavudine/nelfinavir combination had no deleterious effects on the concepts.

PMID- 21860930
TI  - [Relationship between quality of life and vertebral fracture in older women
      living in Southern Brazil].
AB  - PURPOSE: To investigate the relationship between quality of life and spinal
      fracture in women aged over 60 living in Southern Brazil. METHODS: A case-control
      study was conducted with the application of the WHOQOL-bref questionnaire to 100
      women living in the city of Chapeco (SC), aged over 60, postmenopausal, white or
      Caucasian, with no important cognitive impairment or a history of diseases known
      to affect bone metabolism, or malignant neoplasias. The population was divided
      into two groups depending on the presence or absence of fractures in the spine
      radiography. We analyzed variables related to the current and previous medical
      history, life habits and family history of fractures, and the domains and facets
      that compose the WHOQOL-bref. All participants were informed about the objectives
      and methodologies adopted and gave written informed consent to participate in the
      study. RESULTS: The mean age of the women in the fracture group was older than
      that of women with fractures (p<0.05). Also women with fractures tended to belong
      to a higher social class, to have more years of study, a higher family income,
      and a greater use of alcoholic drinks (p<0.05). In the evaluation of the WHOQOL
      bref domains, the fracture group had the highest average in the psychological
      field (chi=63.6+/-3.0) and the lowest in the environment field (chi=9.3+/-58.8).
      In the group without fracture, the highest average also occurred in the
      psychological domain (chi=67.2+/-9.3) and the lowest in the field of social
      relations (chi=57.5+/-7.7). Statistical analysis showed no significant
      correlation between the averages of the facets that make up the areas between the
      groups with and without fractures. CONCLUSIONS: This study suggests that there is
      no impairment of quality of life among older women with vertebral fractures, but
      the relation between QL and time of occurrence and severity of the fractures
      should be better evaluated. Both groups had higher scores in the psychological
      domain, showing that the respondents rely on personal beliefs, spirituality and
      religion, accept their physical appearance while maintaining self-esteem and the
      ability to think, to learn and to concentrate despite the presence of this
      disease. There was no statistically significant difference between groups or
      between domains in the same group.

PMID- 21860931
TI  - [Papanicolaou smear screening: coverage in two home surveys applied in the city
      of Sao Paulo in 1987 and 2001-2002].
AB  - PURPOSE: To compare the coverage of conventional Papanicolaou cytology in women
      aged 15 to 59 years between two home surveys, related to some personal attributes
      and to the tendency to die from cervical cancer. METHODS: We analyzed data
      collected in two home surveys, with complex sampling, in the city of Sao Paulo,
      Brazil, over the years from 1987 to 2001 and 2002. The self-reported answers of
      968 women in the first inquiry and of 1,125 women in the second inquiry were
      compared regarding the reply to the question about the execution of the
      Papanicolaou test "sometimes in a lifetime" in relation to age distribution,
      black skin, marital status, years of education and tendency to die because
      cervical cancer during the period from 1980 to 2007. The Fisher exact test was
      used to compare the sample regarding each item, with the level of significance
      set at p value >5%. RESULTS: From the first to the second inquiry there was a 24%
      increase in the execution of conventional Papanicolaou cytology (from 68.8% to
      85%). The greatest variations in the increased coverage related to the personal
      attributes of the women were detected in black skin color, among single women and
      among women of lower schooling. Regarding the tendency to mortality rates due to
      cervical cancer, no clear ascending or declining tendency was observed along the
      28 years studied (1980 to 2007). CONCLUSION: There was an increase in access to
      the cytological Papanicolaou test among the most vulnerable women. Since 2001 and
      2002, the 85% coverage already reached WHO recommendation, although without a
      clear trend of decline in mortality due to cervical cancer in the following
      years, indicating that screening is only part of an effective and organized
      program for the control of cervical cancer, whose model must guarantee full
      women's health care.

PMID- 21860932
TI  - [Subfertility phenotype, chromosome polymorphism and conception failures].
AB  - PURPOSE: To evaluate the prevalence of cytogenetic alterations and chromosomic
      polymorphism in couples with a subfertility phenotype in a Brazilian population.
      METHODS: Karyotype analysis through G and C banding of 1,236 individuals who
      presented the subfertility phenotype, from two different centers (public and
      private) were included in the study. These patients were classified in two sub
      groups: one with two or more gestational consecutive losses or not and the o
      with, at least, one gestacional loss or absence of conception. Karyotype results
      were evaluated in different groups and frequencies were calculated. Statistical
      analyses were carried out through Fisher's exact test and Odds Ratio analysis.
      RESULTS: Approximately 25% of the cases presented abnormal karyotype results,
      including numerical and structural alterations and also polymorphic variants. In
      both centers, the prevalence of polymorphic variants was 8.9 and 3.8%,
      respectively. CONCLUSIONS: There was no significant difference between the
      prevalence of polymorphic variants and other abnormalities in individuals with or
      without previous history of reproductive loss. The results of the present study
      reinforce the need of adequate disclosure of complete cytogenetic information in
      the karyotype results, with specific attention in relation to the polymorphic
      variants.

PMID- 21860933
TI  - [Strategies directed to professionals for reducing unnecessary cesarean sections
      in Brazil].
AB  - Brazil is among the countries with the highest cesarean section rates, especially
      in the supplementary health sector. However, some characteristics are similar in
      both the public and private sectors in terms of the wishes and expectations of
      pregnant women regarding their delivery. There is a preference for vaginal
      delivery among women of all social, economic, and cultural levels, a fact that
      shifts the focus of the negative influence of this variable from women to other
      subjects involved in delivery care. No isolated factor is able to justify the
      complexity of making a decision for cesarean section, but the physician and the
      type of hospital are the main associated factors. The several harmful effects of
      a non-judicious performance of cesarean section are scientifically recognized. It
      is important to raise the awareness of doctors and of other health professionals
      about the real consequences of this decision, the ethical deviations when
      conducts are chosen without exclusively focusing on the patient's health, and the
      need for constant updating for the management of the various possible conditions
      of childbirth.

PMID- 21860934
TI  - [Production of knowledge and an inter-sectoral approach vis-a-vis living and
      health conditions of workers in the sugarcane sector].
AB  - This article presents some dimensions of inter-sectoral action aimed at improving
      working and living conditions of workers in the sugarcane and alcohol industry.
      The dynamics of the implementation of certain forms of given intersectoral
      practices established in a region of the State of Sao Paulo are analyzed. The
      important role played by sectors of the Labor Prosecution Office and the
      Legislative Authority in the articulation of institutional actors and civil
      society is stressed. They give greater impetus to the work of each public sector
      responsible for addressing the issues of workers'healthcare. This study was
      produced from analysis of documents and material provided by institutions and
      discussion forums with proposals for intervention. The results show that the
      appropriation of strategic knowledge produced by researchers of the sugarcane
      industry in the instrumental resources used in legal actions, monitoring and
      surveillance generates important advances in the health of workers and the
      environment.

PMID- 21860935
TI  - [Workers'health surveillance and academic production: a vital link].

PMID- 21860936
TI  - [Burnout among Family Healthcare physicians: the challenge of transformation in
      the workplace].
AB  - The scope of this paper is to understand how conflicts with the institution and
      disagreements regarding team members'attributions are interpreted by Family
      Healthcare physicians from the burnout perspective. Qualitative research was
      conducted with 24 doctors in Recife between August 2005 and November 2006 based
      on management evaluation (geographic access, conflicts within the team, between
      teams and the District, between the team and the community and public violence in
      the area), and four teams were selected in each of the six Health Districts. Semi
      structured interviews were then conducted. An enormous discrepancy between the
      expectations of physicians and the reality of the workplace was detected. They
      reject the institutional consultation priority and demands for productivity. They
      suffer from what they consider loss of professional identity, with nurses
      attributions questioning the historic essence of their practice. There is
      discredit concerning change and a desire to abandon the profession, especially
      amongst those with the highest expectations concerning conversion of the model. A
      broad set of elements was detected that favor simultaneous exhaustion and
      professional inefficiency and provoke negative attitudes, stressing the need for
      promoting health in the workplace.

PMID- 21860937
TI  - [Non-industrial labor, internal conditions and repetitive strain injury: a case
      study in a shellfish-rearing community on Mare Island, State of Bahia, Brazil].
AB  - Non-industrial labor is still widespread in Brazil. An appropriate approach ought
      to consider different social specificities from those of salaried-work relations.
      The scope was to examine non-industrial work practices, specifically those of
      extractive shellfishing, and their relation to health conditions in a small-scale
      fishing community. It focused on the cadences and time contingencies, as well as
      other working conditions, related to the development of ailments such as
      repetitive strain injury -RSI. A qualitative-ethnographic study was conducted
      between 2005 and 2007 in a community of 800 inhabitants, located on Mare Island
      in the state of Bahia. In a population consisting of fishing households, thirty
      families were interviewed, observed at work and - in cases of suspected RSI 
      referred to a specialized health service. The seriousness of the working
      conditions became evident, especially with respect to RSI. By way of
      illustration, an average frequency of 10,200 repetitive movements per hour were
      verified in extractive shellfishing, while the official Brazilian norm (NR17) for
      a keyboarder establishes a maximum of 8,000 movements per hour. This suggests
      that women shellfishers ought to be included in repetitive strain injury risk
      groups.

PMID- 21860938
TI  - [Decisive factors relating to workload in a primary healthcare unit].
AB  - Work-related diseases o either physical or emotional origin have been on the
      increase in contemporary society in the different work sectors. They have had a
      profound impact on health professionals, such as physicians, dentists, nurses,
      nursing assistants and administrative assistants in the primary healthcare units.
      This study aimed to establish the decisive factors relating to workload, seeking
      to identify possible relations between the working conditions and their potential
      impact on worker health. Thirty-one individuals comprised the sample, namely 12
      physicians, 3 dentists, 1 nurse, 9 nursing assistants, 3 dental assistants and 3
      business assistants at a PHU (Primary Healthcare Unit) in a city in the interior
      of the State of Sao Paulo. For the data collection, structured interviews were
      conducted through meetings with the specific groups of workers, such that a
      detailed description of the activities performed by each group could be drafted,
      as well as a survey of the problems and desirable features involved. The results
      indicated the presence of physical, cognitive and psychological demands;
      inadequate communication processes; obsolete equipment; excessive number of users
      and an inefficient structure to deal with absenteeism.

PMID- 21860939
TI  - [Factors associated with the lifestyle of military police officers].
AB  - The scope of this investigation was to analyze the association between lifestyle
      and socio-demographic and occupational characteristics among military police
      officers (MPs). This involved a cross-sectional epidemiological study. The sample
      consisted of 288 MPs within the Police Force of Recife, Pernambuco. The data were
      collected by means of a semi-structured questionnaire. For the data analysis, IT
      tools were used (STATA-10.0 and SPSS- 15.0 for Windows) and descriptive
      statistics procedures, chi-square analysis and regression associations (p <
      0.05). Among the lifestyle results, 12% said that they smoked, 10% were
      classified as cases of suspected excess consumption of alcoholic beverages, 73%
      were considered to be insufficiently active and 40% admitted they were involved
      in frequent or occasional conflicts. Age of 39 years or over (RP = 1.39), lower
      education level (RP = 1.68), the lowest economic level (RP = 1.49) and being in
      the profession for 18 years or more (RP = 1.49) were associated with lifestyles
      with greater risk to health (with two or more unhealthy factors). Therefore,
      promotion and prevention measures should be adopted in order to attempt to reduce
      the health vulnerabilities of these workers.

PMID- 21860940
TI  - [What garbage represents for municipal collectors and recyclers in Fortaleza,
      State of Ceara (Brazil)].
AB  - This study sought to elicit a discussion about the significance of garbage from
      the standpoint of a group of municipal garbage collectors and garbage recyclers
      resident in Fortaleza, State of Ceara. Using qualitative methodology and the
      individual interview technique, this work presents the results of ongoing
      research that has been conducted together with the employees involved in the
      collection of household garbage in Fortaleza, State of Ceara, and those working
      in a plant for separating recyclable materials. During the period under analysis
      of the "world of garbage" eight interviews were staged. After transcription and
      interpretation of the interviews, it became clear that the respondents perceive
      garbage as being prejudicial to health (due to the various diseases it causes)
      and also as a means of survival (as a result of non-inclusion in the labor market
      due to lack of study and/or opportunity).

PMID- 21860941
TI  - [Silicosis among former copper mine workers].
AB  - There is a dearth of Brazilian studies analyzing the effect of ongoing exposure
      to silica among former copper mine workers, as radiographic readings for
      silicosis have received widespread medical attention. The scope of this study is
      to investigate the clinical and radiological manifestations of silicosis among
      former copper mine workers. A sample of 100 former copper miners had their
      clinical and occupational histories recorded and underwent chest radiography in a
      cross-sectional study that included personal interviews in which their age, sex
      and time worked in copper extraction were recorded. Patients with recent chest X
      Rays brought them with them, or they signed a term of consent and X-Rays were
      taken and analyzed by the radiologist using the Student t Test and Pearson test.
      Among the 100 miners, 35% had silicosis, 11% had conditions other than silicosis,
      such as tuberculosis, emphysema, chronic pulmonary obstructive disease, and 54%
      had no pulmonary lesions. The high incidence of silicosis reinforces the
      recommendation that exposure should be halted as soon as an X-ray detects the
      condition.

PMID- 21860942
TI  - [Work-related musculoskeletal disorders: the profile of workers receiving welfare
      benefit in Diamantina (MG, Brazil)].
AB  - The objective of this study was to identify the profile of workers receiving
      temporary or permanent benefit for Work-Related Musculoskeletal Disorders (WMSD)
      at the Social Welfare Office in Diamantina between 2002 and 2005, and to compare
      the prevalence among this population. The sample was obtained through analysis of
      the database containing socio-demographic and clinical variables, and the profile
      was similar over the years. The most prevalent characteristics were among workers
      resident in Diamantina, between 40 and 59 years of age of elementary educational
      level and without difference in gender. The majority were employed in the service
      sector, with income below US$200 per month. The benefit granted most frequently
      was social welfare due to illness, the most common diagnosis being back pain with
      duration of benefit of 10 months. An increase in the incidence of WMSD was
      observed leading to a marked rise in social welfare retirement due to disability
      over the years. This study made it possible to establish the profile of workers
      retired due to WMSD in Diamantina. This tendency of growth in retirement indices
      reflects the world tendency. The need to implement prevention, promotion and
      rehabilitation policies for the health of this population arises as a clear
      priority from this study.

PMID- 21860943
TI  - [The perception of urban garbage collectors of Dourados, in the state of Mato
      Grosso do Sul, regarding the biological risks involved in their work routine].
AB  - There are several occupational risks inherent to urban garbage collection, and
      the scope of this study was to identify the biological risks to which urban
      garbage collectors in Dourados/MS are exposed. A qualitative study using the
      Lefevre and Lefevre Collective Subject Discourse method was used with 42 urban
      garbage collectors working for the outsourced provider to the Municipal
      Department of Urban Services. Data were collected from September 2005 to January
      2006. The interviews had an average duration of 40 minutes, and were recorded at
      the company office when the workers arrived to start their working day and
      subsequently transcribed. The biological risks mentioned by the garbage pickers
      were accidents with glass, syringes, thorns, dog bites, and contact with
      substances found in the garbage. Accidents with sharp and jagged instruments are
      ways for microorganisms such as bacteria, viruses and fungi to infect the human
      body. Virus contamination, like HIV and Hepatitis B and C, can occur in accidents
      involving inadequate disposal of contaminated needles. The conclusion reached is
      that biological risks in urban garbage collection can be reduced by educating the
      population about adequate garbage disposal.

PMID- 21860944
TI  - [Factors associated with metabolic syndrome in administrative workers in the oil
      industry].
AB  - This is a cross-sectional study seeking to identify the factors associated with
      metabolic syndrome in administrative workers of an oil company. A total of 1,387
      workers were examined, including their anthropometric and biochemical data,
      lifestyle, demographic and socioeconomic characteristics. Metabolic syndrome was
      defined in accordance with the First Set of Brazilian Guidelines for the
      Diagnosis and Treatment of Metabolic Syndrome. Factors associated with MS were
      examined by univariate and multivariate logistic regression models and 15% of the
      workers had MS symptoms. Multivariate analysis revealed that gender (OR=3.4; IC
      95% 2.1- 5.5), age (OR=3.8; IC 95% 1.5-9.4) and smoking (current and past)
      (OR=1.6; CI 95% 1.2-2.3), were associated with metabolic syndrome. In conclusion,
      the prevalence of MS in administrative workers of the oil industry is high,
      especially among males, smokers, ex-smokers and those aged 40 years or more.
      Possibly, the greatest value of this diagnosis is to make it possible to identify
      workers with severe metabolic changes, which would justify the implementation of
      immediate intervention to reduce the identified risk factors. In this sense,
      actions aiming to promote a healthy lifestyle can be developed by the companies,
      in order to enhance the health and quality of life of their employees.

PMID- 21860945
TI  - [Reflections on and contributions to the Ministry of Health's Integrated Plan on
      Health Surveillance Actions for People Exposed to Pesticides].
AB  - This paper highlights the issue of human and environmental contamination caused
      by abusive and undue use of pesticides and of its consequences for human health
      and the environment. It seeks to present reflections on and contributions to the
      Ministry of Health's Integrated Plan on Health Surveillance Actions for People
      Exposed to Pesticides arising from the Federal District Assessment and Control
      Project for Human and Environmental Exposure. The methodology used in this study
      consisted of reading and analysis of reports from the aforementioned projects, as
      well as participating in preliminary meetings for drafting the General
      Coordination Plan for Environmental Health Surveillance and the workshop entitled
      "The integration of Occupational Health Surveillance and Sanitary Vigilance: the
      information issue." This was coordinated by the Occupational Health Working Group
      of the Brazilian Public Health Association and in meetings and workshops of the
      Federal District Project. The outcome of the discussions suggests that the
      investigation strategy used is a positive contribution and that the Federal
      District Project may serve as a pilot project for the Ministry of Health's
      Integrated Plan.

PMID- 21860946
TI  - [The social representations of workers regarding the Family Health Program].
AB  - The scope of this study is to analyze the social representations of workers
      regarding the Family Healthcare Program (FHP) to check its potential and
      limitations in order to change the healthcare model. Data were obtained through
      semi-structured interviews with eighteen health workers and by observing the
      working process of the teams of the Healthy Family Program (HFP) of five Regional
      Administrations in the Federal District. The data obtained from the interviews
      were analyzed using ALCESTE software, which generated two main trends. The first
      is related to social representations of the FHP, composed of several classes: the
      first class deals with FHP as a strategy to change the healthcare model; the
      second class refers to the difficulties of infrastructure, and the fifth class
      deals with family interaction based on medical practice. The second trend deals
      with daily practices of the HFP, composed of a third class, namely the actions
      developed by the HFP, and a fourth class that demonstrates the forms of
      organization and division of labor.

PMID- 21860947
TI  - [The interface of public healthcare with the health of the oceans: proliferation
      of disease, socio-economic impacts and beneficial relationships].
AB  - Over the past decades, human activities have had a heavy impact on the marine
      environment, causing alterations in ecological processes. The relationship
      between the health of the oceans, human activities and public healthcare is
      already generally accepted, though the mechanisms involved are still under
      scientific scrutiny. These relationships include a focus on climate change, toxic
      algal blooms, microbial and chemical contamination in marine waters and
      bioinvasion by exotic species. Moreover, there is the beneficial effect of the
      oceans on human health and wellbeing, such as natural products for the human
      diet, the development of biomedicine, or simply the satisfaction derived from
      human recreation, sports and other interactions of humans with oceans. The
      importance of appreciating the link between public healthcare and the health of
      the oceans is especially important due to the growing number of people living in
      coastal areas, mainly in tropical and subtropical regions. The backcloth to this
      is risk-related human activities that pose a danger to marine environmental
      health and the increase in the vulnerability of humans and biodiversity and socio
      environmental iniquity.

PMID- 21860948
TI  - [Study of the association between socio-environmental factors and the prevalence
      of intestinal parasitosis in the suburbs of the city of Manaus in the state of
      Amazonas, Brazil].
AB  - This study assesses the association between socio-environmental factors and urban
      sanitation conditions with the prevalence of intestinal parasitosis in a
      community on the periphery of the city of Manaus. The study comprised a socio
      environmental survey and a parasitological inquiry. A heterogeneous community was
      revealed with some socio-economic and environmental differences between the micro
      areas evaluated, even though the urban sanitation conditions were found to be
      predominantly precarious. The prevalence of intestinal parasitosis was 44.2%.
      There was no significant difference between the micro-areas that could explain
      the occurrence of intestinal parasitosis. An association was found between
      intestinal parasitosis and residential building types, age bracket and the
      quality of the water used for personal hygiene and consumption in the home. Open
      air sewage was a risk factor associated with intestinal parasitosis (OR=6.72;
      p=0.034) and also with intestinal protozoa (OR=21.87; p=0.004). In terms of the
      presence of protozoa, two risk factors were verified: the dumping of sewage
      directly into the river system (OR=12.98; p=0.011) and the use of rudimentary
      cesspits (OR=9.54; p=0.019).

PMID- 21860949
TI  - [Intoxication due to pesticides in the Federal District of Brazil between 2004
      and 2007 -analysis of notification to the Toxicological Information and
      Assistance Center].
AB  - Exposure to toxic substances, including pesticides, can cause irreversible damage
      to humans, including death, and is therefore considered a serious public health
      problem worldwide. This is a retrospective study using data gathered by the
      Toxicological Information and Assistance Center of Brazil's Federal District
      (Ciat-DF) between 2004 and 2007. During this period, 709 intoxications with
      pesticide occurred in the DF and were analyzed in this study. Fifty-one percent
      of the intoxicated individuals were men; the events occurred mostly in the home
      (91%), in the urban area (86.3%) and by ingestion (84%). Children from 1 to 4
      years of age and adults from 20 to 39 years were involved in 30% and 36% of the
      cases, respectively. Accidental intoxication corresponded to 47.1% of the cases,
      followed by attempted suicide (44.2%). The illegal rodenticide known as
      "chumbinho", the main ingredient of which is carbamate insecticide aldicarb, was
      involved in 35.1% of the cases, mostly in suicide attempts. In eighteen cases,
      the intoxicated individuals died after exposure to the pesticides, namely 15
      suicides and 3 accidental poisonings. When compared with other data sources, this
      study identified a high level of underreporting to the Ciat-DF of intoxication by
      pesticide during the period under study.

PMID- 21860950
TI  - [Community clinical toxicology].
AB  - In some Latin American countries acute intoxication is professionally managed by
      specialized physicians qualified in the area. Something similar occurs with work
      related chronic intoxication in the formal sector. However, a different reality
      prevails for the assessment of chronic intoxication of environmental origin,
      since it is by definition more difficult to diagnose. For treatment of acute
      intoxication, Toxicological Information and Care Centers have been set up, though
      similar bodies have not been created for chronic environmental intoxication.
      Therefore, in this study a model of chronic intoxication care is proposed, using
      multidisciplinary teams adopting a new approach, namely Community Clinical
      Toxicology, the goal of which would be the simultaneous care of acute
      intoxication which is generally treated in hospital, and environmental
      intoxication that is normal dealt with at community level. The ultimate goal is
      to take advantage of the expertise that exists in the Region in terms of Clinical
      Toxicology to organize community work.

PMID- 21860951
TI  - [Influence of different concentrations of fluoride in the water on epidemiologic
      indicators of oral health/disease].
AB  - The scope of this study was to evaluate access to fluoride sources and oral
      health hygiene of 237 schoolchildren aged nine to sixteen, from three locations
      with different fluoride concentrations in the water. The fluoride level in the
      water of each area was analyzed by the selective electrode technique for the
      fluoride ion and the prevalence of dental caries and fluorosis were evaluated,
      respectively, by the DMFT and TSIF index, revealing a statistically significant
      difference (ANOVA; p <0,05) in the three locations: area without artificial
      fluoridation (DMTF 5.32 +/- 3.49) and 16% of dental fluorosis; area with
      artificial fluoridation of 0.8 ppmF (DMTF 1.88 +/- 2.22) and 94% of dental
      fluorosis; area with natural fluoridation of 2.54 ppmF (DMTF 3.96 +/- 2.38) and
      100% of dental fluorosis. The findings suggest that the epidemiologic indicators
      of oral health/disease are influenced by the presence of fluoride in the water
      supply and that supervision and orientation are fundamental in the correct use of
      fluoridated compositions, taking advantage of the maximum benefit in the control
      of dental caries with minimum risk of the occurrence of dental fluorosis.

PMID- 21860952
TI  - [Evaluation of the impact of exposure to pesticides on the health of the rural
      population: Vale do Taquari, State of Rio Grande do Sul (Brazil)].
AB  - The scope of this cross-sectional study was to assess a possible link between
      contact with pesticides and the prevalence of chronic disease in the rural
      population in the south of Brazil. Three municipalities were randomly chosen. The
      sample selected was recruited over three months (2005) and was composed of 298
      subjects of both sexes, between 18 and 65 years of age, who frequented public or
      private pharmacies for the purchase of medication. Data obtained by means of
      structured interviews revealed that 68.4% of those interviewed worked in rural
      activities, and 74.8% of these were members of families working in agriculture
      with contact with pesticides. The average age was 51+16.5 years of age for the
      interviewees with contact with pesticides and 50+17.9 years for those without
      contact. The sample was composed of 36.2% of men, and 57.7% of the individuals
      had more than four years of education. Direct or indirect contact with pesticides
      was associated with the report of several diseases, with neurological and oral
      diseases being the most prevalent. There was a link with painful conditions and
      individuals with contact with pesticides reported twice as many diseases. The
      data corroborate the literature and draw attention to the need for promoting
      measures to protect the health of the rural population.

PMID- 21860953
TI  - [The impact of human activities on the dynamics of phosphorus in the environment
      and its effect on public health].
AB  - Phosphorus is a nutrient with finite and non-renewable sources, the speed of
      exploitation of which is currently far higher than the rates of return to its
      natural cycle. It is already being predicted that available and known sources
      will soon be exhausted, with serious and irreversible economic, social and
      environmental impacts. In this context, this study sets out to present
      information about the dynamics of phosphorus in the environment, assessing the
      impacts caused by human activities and establishing what actions might contribute
      to preservation of the nutrient cycle. To contribute to enhanced understanding of
      the topic, the evolution of data on population density, the number of industries
      and the extension of cultivated areas in a river basin, was studied over 22 years
      in relation to concentrations of phosphorus in water and sediment. The Tiete
      River was used for the case study. The results revealed that the control of
      domestic effluent, especially the amount of sodium tripolyphosphate (STPP) used
      in detergents and soap products, is of major importance for improving water
      quality, ensuring environmental protection and safeguarding public health.

PMID- 21860954
TI  - [Collective action and veto players in public policy: the sanitation policy in
      Brazil (1998-2002)].
AB  - In 1999, the federal government has committed itself to the IMF with the
      privatization of the sanitation and other public services, seeking resources to
      address the fiscal crisis. He proposed the bill 4147/01 as the regulatory
      framework that would provide the necessary security for investors interested in
      acquiring the state-owned sanitation enterprises. Against this initiative, a
      coalition of industry interests mobilized in order to veto the adoption of
      privatization: the National Front for Environmental Sanitation (FNSA). This paper
      identifies the actors, the agenda and the interests involved in this political
      coalition. It shows that the coalition acted decisively as an instance of veto,
      limiting the effects of the agreement with the IMF on the public policy of
      sanitation in Brazil this time.

PMID- 21860955
TI  - [Vulnerability of management of waste from health services in Joao Pessoa, State
      of Paraiba (Brazil)].
AB  - The discussion in the academy on solid urban waste residues (UWR) is analyzed,
      with health service waste (HSW) being an integral part of UWR, not necessarily in
      terms of the amount generated, but due to the risk potential to collective and
      environmental health. The scope of the study was to verify the vulnerability of
      UWR handling in primary, secondary and tertiary healthcare units in Joao Pessoa
      in the state of Paraiba. This involved a quantitative, exploratory and
      descriptive investigation of the handling of UWR, using a checklist and
      analytical evaluation of the vulnerability of HSW handling for data collection.
      It was detected that 21.05% of the establishments failed to separate hazardous
      waste, 26.34% did not standardize plastic disposal bags, and 47.37% of the
      workers responsible for collection were not trained to handle HSW. It was
      concluded that the vulnerability of HSW handling in Joao Pessoa in the order of
      48.02%, was significant, potentially contributing to the deterioration of
      environmental and collective health and leading to a public health problem.

PMID- 21860956
TI  - [The ecological debate from the hospital workers' standpoint].
AB  - This study seeks to ascertain what hospital workers think about the ecologic
      debate, looking for opinions that may elicit a discussion about the development
      of responsible actions to be taken by this group in the context of hospital work.
      The theoretical benchmark used for this discussion is based on the Reflexive
      Modernization and the Risk Society concept proposed by contemporary sociologists.
      This involved qualitative research using case study strategy and it was carried
      out with hospital workers at a public institution. The data were collected using
      document analysis, field observation and individual and group interviews. The
      study revealed that hospital workers take a somewhat distant view in terms of the
      environmental issue, which is reflexively affected by the current ecological
      debate. This concept has the influence of specific factors in the context of
      hospital work. In conclusion, the importance of educational actions together with
      the workers was identified, in order to establish more responsible actions with
      respect to environmental preservation.

PMID- 21860957
TI  - [Labeling of food containing genetically modified organisms: international
      policies and Brazilian legislation].
AB  - The increase in surface area planted with genetically modified crops, with the
      subsequent transfer of such crops into the general environment for commercial
      trade, has raised questions about the safety of these products. The introduction
      of the Cartagena Protocol on Biosafety has led to the need to produce information
      and ensure training in this area for the implementation of policies on biosafety
      and for decision-making on the part of governments at the national, regional and
      international level. This article presents two main standpoints regarding the
      labeling of GM products (one adopted by the United States and the other by the
      European Union), as well as the position adopted by Brazil and its current
      legislation on labeling and commercial release of genetically modified (GM)
      products.

PMID- 21860958
TI  - [Air pollution in internal environments and sick building syndrome].
AB  - Indoor Air Quality (IAQ) emerged as a science from the 1970s onwards with the
      energy crisis and the subsequent construction of sealed buildings (without
      natural ventilation). This mainly occurred in developed countries and it soon
      came to public attention that lower levels of air exchange in these environments
      was the main culprit for the increase in concentration of indoor air pollutants.
      It is common knowledge that ventilation is one of the principal factors that
      interfere with air quality in indoor environments and that the occupants
      contribute to the pollution of these environments with their activities.
      Furthermore, poor indoor air quality is associated with some diseases (cough,
      rhinitis, allergy, etc.) and with Sick Building Syndrome (SBS). For sampling of
      the indoor contaminants there are several methodologies, available including
      passive monitoring systems, active and automatic systems. To ensure a healthy
      indoor environment, the application of specific legislation needs to be
      reconciled with research and fostering awareness among the occupants of such
      buildings. This survey seeks to identify the different contaminants found in
      internal environments, their effects on human health and the methodologies
      available for sampling them.

PMID- 21860959
TI  - [Patient safety and safety culture: review of the literature].

PMID- 21860960
TI  - [Mental health and interdisciplinary work: the experience in "Candido Ferreira",
      in Campinas, State of Sao Paulo, Brazil].
AB  - This article analyses the process on the psychiatric reform, with a focus on the
      interdisciplinary work developed by the health professionals from the health
      service "Dr. Candido Ferreira"in Campinas, Brazil. This is a philanthropic
      institution which contributes significantly to public mental health network in
      this city. Even though the service is integrated to the Unified Heath System
      (SUS), it presents a financial, administrative and managerial independence, which
      allows implementing some therapeutic experiences and managerial innovations. More
      specifically, this article focuses on the process of decision making by the
      interdisciplinary team, involving diagnosis and therapeutic process. Other
      themes, related to the organization of the service in the process of
      dehospitalization, are considered, such as the transfer of patients into
      residences outside the institution, the maintenance of these units, the
      management of the workshops in the institution which allows a financial income
      for the patient, and the beginning of the institution as a three years residence
      in Psychiatry. The methodological approach of the research is essentially
      qualitative, drawing from interviews and participant observation, related the
      professionals from this service.

PMID- 21860961
TI  - Lung cancer risk in painters: a meta-analysis.
AB  - We conducted a meta-analysis to quantitatively compare the association between
      occupation as a painter and the incidence or mortality from lung cancer. PubMed
      and the reference lists of pertinent publications were searched and reviewed. For
      the meta-analysis, we used data from 47 independent cohort, record linkage, and
      case-control studies (from a total of 74 reports), including > 11,000 incident
      cases or deaths from lung cancer among painters. Three authors independently
      abstracted data and assessed study quality. The summary relative risk (meta-RR,
      random effects) for lung cancer in painters was 1.35 [95% confidence interval
      (CI), 1.29-1.41; 47 studies] and 1.35 (95% CI, 1.21-1.51; 27 studies) after
      controlling for smoking. The relative risk was higher in never-smokers (meta-RR =
      2.00; 95% CI, 1.09-3.67; 3 studies) and persisted when restricted to studies that
      adjusted for other occupational exposures (meta-RR = 1.57; 95% CI, 1.21-2.04; 5
      studies). These results support the conclusion that occupational exposures in
      painters are causally associated with the risk of lung cancer.

PMID- 21860962
TI  - [Standardization of toxicological information in Brazil].

PMID- 21860964
TI  - Otolaryngologists in facial plastic surgery, yes.

PMID- 21860965
TI  - Comparison of clinical characteristics of patients with adductor laryngeal
      dystonia in the focal and segmental types.
AB  - Dystonia is a central motor processing neurological disorder characterized by
      abnormal, often action-induced, involuntary movements or uncontrolled spasms.
      AIM: To compare patients with the diagnoses of focal and segmental adductor
      laryngeal dystonia at the Neurolarynx Outpatient Clinic of the Federal University
      of Sao Paulo. MATERIALS AND METHODS: A clinical retrospective study of data
      collected from patient registries from 2003 to 2009. RESULTS: Of 34 patients, 25
      presented focal dystonia and 9 presented segmental dystonia. There were 30
      females (88. 2%) and 4 males (11. 8%). A relation with a traumatic event was
      reported in 11 cases (32. 4%). Vocal tremor was observed in 21 patients (61. 8%).
      The mean age at onset, the age at diagnosis, and time between the onset and the
      diagnosis were respectively 55, 61. 3 and 6. 3 years. There was no statistical
      difference between patients with focal laryngeal adductor dystonia and segmental
      dystonia in the study data. CONCLUSIONS: There were no statistical differences
      among patients with focal adductor laryngeal dystonia and segmental dystonia
      relating to age of onset, age of diagnosis, gender, time between onset and
      diagnosis, presence of associated tremor, and relation to trauma.

PMID- 21860966
TI  - Temporomandibular disorder and generalized joint hypermobility: application of
      diagnostic criteria.
AB  - Generalized joint hypermobility (GJH) has been considered a predisposing factor
      for the development of temporomandibular disorder (TMD). AIM: To evaluate
      clinical and psychosocial aspects in individuals diagnosed with TMD with or
      without GJH. MATERIALS AND METHODS: Clinical and experimental study, which
      enrolled 34 women, from 18 to 35 years of age with TMD diagnosed by RDC/TMD. The
      GJH was assessed by the Beighton score and volunteers were broken down into 2
      groups: with GJH (n = 22) and without GJH (n = 12). RESULTS: We found a high
      percentage of GJH (64. 71%). All participants had myofascial pain; 79. 41% had
      arthralgia and 41% had disk displacement. There was a correlation between higher
      GJH scores and higher passive mouth opening amplitude (p = 0.0034), with pain (p
      = 0.0029) and without pain (p = 0.0081). Greater mandibular range of motion was
      observed in the group with GJH, except for protrusion. Painful mouth opening was
      statistically higher in the GJH group (p = 0.0279). CONCLUSIONS: Individuals with
      TMD associated or not to GJH do not differ significantly regarding clinical and
      psychosocial aspects, except in the mandibular opening range of motion, which if
      kept at physiological levels can lead to a late diagnosis of TMD in these
      individuals.

PMID- 21860967
TI  - Clinic-epidemiological analysis of an otorhinolaryngology emergency unit care in
      a tertiary hospital.
AB  - Emergencies are common in our Otorhinolaringology specialty. However, the
      clinical and epidemiological features are not very well known. OBJECTIVES: To
      evaluate the clinical and epidemiological profiles of otorhinolaryngological
      disorders in an emergency unit of a tertiary hospital, and to determine the
      appropriateness of the level of health care for a tertiary hospital. MATERIALS
      AND METHODS: An analytical study using data records of an otorhinolaryngological
      emergency unit at a tertiary hospital in the Federal District for a year, full
      time, and no screening. The age, sex, arrival time and clinical diagnosis were
      evaluated. The entities were separated into cases of
      pharingolaryngoesthomatology, otology, rhinology, and head and neck surgery.
      These were evaluated according to the urgency level, the required care, and the
      arrival time. RESULTS: 26,584 data records were selected, of which 2,001 were
      excluded. The group comprised 54. 48% women, and 45. 51% men. Otological
      complaints (62. 27%) prevailed. 61. 26% of cases were considered emergencies.
      Only 9. 7% of those required medium or high complex resources for resolution.
      CONCLUSIONS: The study showed that 61. 26% of the otorhinolaryngological cases
      are emergencies, and only 9. 7% required medium or high complexity resources.

PMID- 21860968
TI  - Validity and reliability of the hearing handicap inventory for adults.
AB  - The Hearing Handicap Inventory for Adults (HHIA) translated into Brazilian
      Portuguese has been used for clinical practice and research purposes; however,
      information regarding its ease of reading and psychometric properties are still
      lacking. AIM: To evaluate the ease of reading and psychometric properties of the
      Brazilian translation of this tool, including its validity and reliability.
      MATERIALS AND METHODS: Prospective study. The questionnaire was applied to 30
      normal hearing (Group A) and 113 hearing impaired (Group B) persons. Thirty two
      participants (group B) answered the questionnaire a second time. The Flesch
      readability index was calculated for each item in the questionnaire. The internal
      consistency, test-retest reliability and discriminant validity were evaluated.
      RESULTS: Flesch's scores showed that the questionnaire was easy to read.
      Cronbach's alpha and Pearson's correlation showed high internal consistency.
      There was no significant difference between test and retest scores. Besides,
      correlation between these two scores was also high and significant. Student t
      test indicated significant difference between scores for groups A and B
      (discriminant validity). CONCLUSIONS: The Hearing Handicap Inventory for Adults
      translated into Brazilian Portuguese maintained the reliability and validity of
      the English version. Further studies are needed to determine the convergent
      validity and construct validity for this instrument.

PMID- 21860969
TI  - Bone defect repair on the alveolar wall of the maxillary sinus using collagen
      membranes and temporal fascia: an experimental study in monkeys.
AB  - Few studies has been done using guided bone regeneration in maxillary sinus
      defects. AIM: To assess the bone repair process in surgical defects on the
      alveolar wall of the monkey maxillary sinus, which communicates with the sinus
      cavity, by using collagen membranes: Gen-derm--Genius Baumer, Pro-tape--Proline
      and autologous temporal fascia. MATERIALS AND METHODS: In this prospective and
      experimental study, orosinusal communications were performed in four tufted
      capuchin monkeys (Cebus apella) and histologic analysis was carried out 180 days
      after. RESULTS: In the defects without a cover (control), bone proliferation
      predominated in two animals and fibrous connective tissue predominated in the
      other two. In defects repaired with a temporal fascia flap, fibrous connective
      tissue predominated in three animals and bone proliferation predominated in one.
      In the defects repaired with Gen-derm or Pro-tape collagen membranes there was
      complete bone proliferation in three animals and fibrous connective tissue in
      one. CONCLUSIONS: Surgical defect can be repaired with both bone tissue and
      fibrous connective tissue in all study groups; collagen membranes was more
      beneficial in the bone repair process than temporal fascia or absence of a
      barrier.

PMID- 21860970
TI  - Histomorphometric evaluation of calcium phosphate bone grafts on bone repair.
AB  - Because of its biocompatibility and osteoconductive properties, calcium-phosphate
      cement has been used as bone surrogate. OBJECTIVE: The purpose of this study was
      to do a histomorphometric comparison of bone regeneration using hydroxyapatite
      biphasic ceramic, calcium-phosphate cement and autogenous bone graft. STUDY
      DESIGN: Prospective and laboratorial experiment. MATERIALS AND METHODS: Two 5mm
      in diameter cavities (left and right--test and control) were made in the parietal
      bone of 72 rats. The GI, GII, GIII and GIV test cavities were filled with calcium
      phosphate cement, biphasic ceramic hydroxyapatite, autogenous bone graft and
      blood. The animals were killed at 30, 60 and 90 days and the specimens underwent
      histomorphometric analysis. RESULTS: The results showed that autogenous bone
      graft treated defects had significantly more new bone at 30 days compared to
      other test groups. Within 60 and 90 days, bone formation was more significant in
      the test groups GI, GII and GIII; GI and GII encompassed larger areas. Throughout
      the evaluation periods, GII tests showed more bone formation when compared to GI.
      CONCLUSIONS: Biomaterials depicted a significantly increase in bone content, when
      compared to autogenous bone graft, concerning bone regeneration.

PMID- 21860971
TI  - Ear abnormalities in patients with oculo-auriculo-vertebral spectrum (Goldenhar
      syndrome).
AB  - Oculo-auriculo-vertebral spectrum (OAVS) is a rare condition characterized by the
      involvement of the first branchial arches. PURPOSE: To investigate the ear
      abnormalities of a sample of patients with OAVS. MATERIALS AND METHODS: The
      sample consisted of 12 patients with OAVS seen at the Clinical Genetics Unit,
      UFCSPA/CHSCPA. The study included only patients who underwent mastoid computed
      tomography and with normal karyotype. We performed a review of its clinical
      features, giving emphasis to the ear findings. RESULTS: Nine patients were male,
      the ages ranged from 1 day to 17 years. Ear abnormalities were observed in all
      patients and involved the external (n = 12), middle (n = 10) and inner ear (n =
      3). Microtia was the most frequent finding (n = 12). The most common
      abnormalities of the middle ear were: opacification (n = 2), displacement (n = 2)
      and malformation of the ossicular chain. Agenesis of the internal auditory canal
      (n = 2) was the most frequent alteration of the inner ear. CONCLUSIONS: Ear
      abnormalities are variable in patients with OAVS and often there is no
      correlation between findings in the external, middle and inner ear. The
      evaluation of these structures is important in the management of individuals with
      OAVS.

PMID- 21860972
TI  - Immediate effects of the phonation into a straw exercise.
AB  - Immediate effects of an exercise with the vocal tract semi-closed. OBJECTIVE: To
      investigate the immediate effects of the phonation exercise in a straw in
      individuals with and without vocal fold lesions. MATERIALS AND METHODS:
      Prospective study. 48 individuals, aged between 18 and 55 years participated in
      the study, and they were distributed into two groups: GL- with a benign vocal
      fold lesion; GSL- without a lesion. The following analyses were carried out
      before and after the straw phonation exercises: voice self-analysis, [epsilon]
      vowel auditory-perception analysis, selected parameters acoustics (VoxMetria 2.
      6) and videolaryngoscopy. RESULTS: The vocal self assessment indicated a
      statistically significant improvement on voice emission in GL individuals (p = 0.
      015). There were no statistically significant differences before and after the
      exercise and between the groups, in the videolaryngoscopy, acoustic and auditory
      perception assessments. CONCLUSIONS: The straw phonation exercise caused positive
      effects, seen upon voice self-assessment, indicating an easier and better voice
      upon phonation.

PMID- 21860973
TI  - The quality of life among Otorhinolaryngology residents in Distrito Federal
      (Brazil).
AB  - Otorhinolaryngology residents' quality of life must be investigated during
      medical residency. Work-related factors impacting their lives, such as
      depression, sleep deprivation and excessive work load may impact the well-being
      of these individuals. OBJECTIVE: To assess and discuss the quality of life of
      Otorhinolaryngology Resident Physicians in Distrito Federal (Reuni-ORL).
      MATERIALS AND METHODS: Cross-sectional study, the quality of life of each
      individual was assessed by means of a questionnaire specifically designed for
      this purpose--Whoqol-bref, proposed by the WHO. RESULTS: Males had better
      psychological scores when compared to females (p = 0. 013). Mean scores
      comparison among the years in residency were statistically significant only in
      the psychological domain when comparing the first and second years (p = 0. 046),
      in which 2nd-year residents had the higher scores. CONCLUSIONS: Despite constant
      changes to the ENT program (Reuni-ORL) in the Distrito Federal, aiming at
      improving work and training conditions for residents, there still is a
      psychological burden in their first year of residency.

PMID- 21860974
TI  - Peak nasal inspiratory flow evaluation as an objective method of measuring nasal
      airflow.
AB  - Acoustic rhinometry, rhinomanometry and Inspiratory Peak Nasal Flow (IPNF) are
      used in order to objectively assess nasal patency. These are expensive not very
      practical tests, except for IPNF, which is a fast, simple and low cost method.
      OBJECTIVE: To assess IPNF in healthy individuals complaining of nose obstruction
      caused by allergic rhinitis. METHOD: IPNF use in 78 individuals with and without
      rhinitis symptoms. STUDY DESIGN: Contemporary cross-sectional cohort. RESULTS:
      IPNF showed significant results for nasal obstruction, rhinorrhea, pruritus,
      sneezes and tearing (p < 0. 001). There was no correlation between the presence
      of nasal septum deviation and IPNF (p = 0. 561). We found a positive correlation
      between IPNF and the Visual Analogue Scale (VAS) for nasal obstruction (p = 0.
      002). In the multiple linear regression model, there was a statistical
      significance between the values found in IPNF with allergic rhinitis and age (p =
      0. 005 and p = 0. 023 respectively). CONCLUSIONS: IPNF proved to be a reliable
      method to detect changes in nasal patency, by obstructive causes as well as
      inflammatory causes, with an acceptable level of statistical significance,
      simple, easy to handle, inexpensive and reproducible.

PMID- 21860975
TI  - Auditory neuropathy/Auditory dyssynchrony in children with Cochlear Implants.
AB  - The electrical stimulation generated by the Cochlear Implant (CI) may improve the
      neural synchrony and hence contribute to the development of auditory skills in
      patients with Auditory Neuropathy/Auditory Dyssynchrony (AN/AD). AIM: Prospective
      cohort cross-sectional study to evaluate the auditory performance and the
      characteristics of the electrically evoked compound action potential (ECAP) in 18
      children with AN/AD and cochlear implants. MATERIAL AND METHODS: The auditory
      perception was evaluated by sound field thresholds and speech perception tests.
      To evaluate ECAP's characteristics, the threshold and amplitude of neural
      response were evaluated at 80 Hz and 35 Hz. RESULTS: No significant statistical
      difference was found concerning the development of auditory skills. The ECAP's
      characteristics differences at 80 and 35 Hz stimulation rate were also not
      statistically significant. CONCLUSIONS: The CI was seen as an efficient resource
      to develop auditory skills in 94% of the AN/AD patients studied. The auditory
      perception benefits and the possibility to measure ECAP showed that the
      electrical stimulation could compensate for the neural dyssynchrony caused by the
      AN/AD. However, a unique clinical procedure cannot be proposed at this point.
      Therefore, a careful and complete evaluation of each AN/AD patient before
      recommending a Cochlear Implant is advised. Clinical Trials: NCT01023932.

PMID- 21860976
TI  - Computerized analysis of snoring in sleep apnea syndrome.
AB  - The International Classification of Sleep Disorders lists 90 disorders.
      Manifestations, such as snoring, are important signs in the diagnosis of the
      Obstructive Sleep Apnea Syndrome; they are also socially undesirable. OBJECTIVE:
      The aim of this paper was to present and evaluate a computerized tool that
      automatically identifies snoring and highlights the importance of establishing
      the duration of each snoring event in OSA patients. MATERIAL AND METHODS: The low
      sampling (200 Hz) electrical signal that indicates snoring was measured during
      polysomnography. The snoring sound of 31 patients was automatically classified by
      the software. The Kappa approach was applied to measure agreement between the
      automatic detection software and a trained observer. Student's T test was applied
      to evaluate differences in the duration of snoring episodes among simple snorers
      and OSA snorers. RESULTS: Of a total 43,976 snoring episodes, the software
      sensitivity was 99. 26%, the specificity was 97. 35%, and Kappa was 0. 96. We
      found a statistically significant difference (p <0. 0001) in the duration of
      snoring episodes (simple snoring x OSA snorers). CONCLUSIONS: This computer
      software makes it easier to generate quantitative reports of snoring, thereby
      reducing manual labor.

PMID- 21860977
TI  - Betahistine in the treatment of tinnitus in patients with vestibular disorders.
AB  - Betahistine is a medicine used to treat vestibular disorders that has also been
      used to treat tinnitus. AIM: To assess the effects of betahistine on tinnitus in
      patients with vestibular disorders. MATERIAL AND METHOD: Retrospective data were
      collected from patient records for individuals presenting with vestibular
      dysfunction and tinnitus. Patients included had received betahistine 48 mg/day
      and clinical outcomes were compared with a control group comprising individuals
      who were unable to receive betahistine due to gastritis, ulcers, pregnancy,
      asthma or hypersensitivity to the drug. Patients underwent control of any
      aggravating factors and also standard vestibular exercises as a basis for
      treatment. The intensity, frequency and duration of tinnitus were assessed on the
      first day of dosing and after 120 days of treatment. Clinical improvement was
      defined as a total or partial reduction of tinnitus after treatment. RESULTS:
      Clinical improvement was observed in 80/262 (30. 5%) of patients treated with
      betahistine and 43/252 (17. 1%) of control patients. Betahistine significantly
      (p<0. 0001) improved tinnitus in treated individuals. CONCLUSIONS: The daily
      dosage of 48 mg of betahistine during 120 consecutive days is useful to reduce or
      eliminate tinnitus in patients with vestibular disorders.

PMID- 21860978
TI  - Auditory processing performance in blind people.
AB  - Hearing has an important role in human development and social adaptation in blind
      people. OBJECTIVE: To evaluate the performance of temporal auditory processing in
      blind people; to characterize the temporal resolution ability; to characterize
      the temporal ordinance ability and to compare the performance of the study
      population in the applied tests. METHODS: Fifteen blind adults participated in
      this study. A cross-sectional study was undertaken; approval was obtained from
      the Pernambuco Catholic University Ethics Committee, no. 003/2008. RESULTS:
      Temporal auditory processing was excellent--the average composed threshold in the
      original RGDT version was 4. 98 ms; it was 50 ms for all frequencies in the
      expanded version. PPS and DPS results ranged from 95% to 100%. There were no
      quantitative differences in the comparison of tests; but oral reports suggested
      that the original RGDT original version was more difficult. CONCLUSIONS: The
      study sample performed well in temporal auditory processing; it also performed
      well in temporal resolution and ordinance abilities.

PMID- 21860979
TI  - Crooked nose: outcome evaluations in rhinoplasty.
AB  - A crooked nose is the result of deformities that might involve the bony nasal
      pyramid, the upper and lower lateral cartilages, and nasal septum, causing
      complaints of aesthetic and/or functional nature. PURPOSE: To evaluate how
      satisfied are those patients who underwent rhinoplasty to correct crooked nose,
      through the questionnaire Rhinoplasty Outcomes Evaluation (ROE). MATERIAL AND
      METHOD: A longitudinal study with retrospective analysis of preoperative
      satisfaction and prospective analysis of postoperative satisfaction of patients
      who underwent rhinoplasty. ROE questionnaire was applied twice in the same visit
      aiming at measuring patient satisfaction in both pre and postoperative periods.
      Nineteen patients who underwent rhinoplasty answered the ROE. RESULTS: For all
      patients who underwent rhinoplasty, the average preoperative satisfaction score
      was of 24. 6 +/- 11. 3, while the average postoperative score was of 76. 1 +/-
      19. 5 (p<0. 0001). Average differences between pre and postoperative satisfaction
      scores in patients younger than 30 years of age were lower than those reported by
      >30-year-old patients (p = 0. 05). CONCLUSIONS: From the Rhinoplasty Outcomes
      Evaluation questionnaire, it is possible to demonstrate the impact that
      rhinoplasty to correct a crooked nose determines the quality of life of patients.
      Approximately 90% of patients undergoing rhinoplasty believed they achieved a
      good or excellent postoperative result.

PMID- 21860980
TI  - Anthropometric data as predictors of Obstructive Sleep Apnea Severity.
AB  - The Obstructive Sleep Apnea Syndrome is a chronic disease characterized by
      episodes upper airway collapse, and has been associated with increased
      cardiovascular morbidity. AIM: To correlate the neck, abdominal and pelvic
      circumference with the AHI and oxyhemoglobin saturation in OSA patients, and to
      correlate these values with disease severity. MATERIALS AND METHODS: A
      prospective descriptive study of 82 patients evaluated complaints suggesting OSA,
      from July 2008 to March 2010. All patients underwent polysomnography, an ENT
      clinical exam, measures of the BMI, abdominal, pelvic, and cervical
      circumferences. The mean, standard deviations and Spearman's correlations were
      analyzed. RESULTS: The mean AHI in men was 39 events/hr; in women it was 21
      events/hr in women. The mean neck circumference was 34. 5 cm in women and 41. 3
      cm in men, the mean abdominal circumference was 94. 3 cm in women and 101. 5 cm
      in men, and the pelvic circumference was 105. 7 cm in men and 108. 7 cm in women.
      The neck circumference correlated more closely to the AHI in men (r = + 0. 389 p
      = 0. 001). The relationship between the abdominal circumference correlated more
      with AHI than with the BMI in men (AbC r = + 0. 358 p = 0. 003 BMI r = + 0. 321 p
      = 0. 009). CONCLUSIONS: The neck circumference is the best anthropometric
      measurement of respiratory disorder severity compared to the AbC or the BMI.

PMID- 21860981
TI  - Microbiology of rhinosinusitis in immunosupressed patients from the University
      Hospital.
AB  - Immunosuppressed patients are often susceptible to upper airway infections,
      especially those of the paranasal sinuses. These can sometimes jeopardize
      treatment success and even lead to a fatal outcome. OBJECTIVE: To study the
      paranasal microbiology of immunosuppressed patients with clinical evidence of
      rhinosinusitis, and compare it with that from immunocompetent patients. MATERIAL
      AND METHOD: Retrospective study, in which 42 immunosuppressed and 16
      immunocompetent patients were selected. All had clinically evident acute or
      recurrent rhinosinusitis and were submitted to ethmoidal or sphenoid sinusectomy
      or maxillary sinus puncture to gather material for microbiological cultures.
      RESULTS: There were 92% positive cultures, and 21% were negative. Of the positive
      cultures, 38% were bacterial, with P. aeruginosa being the most frequent agent;
      64% were fungal, which occurred in the most immunocompromised patients. In the
      immunocompetent group, there were 62. 5% positive cultures and 37. 5% negative
      ones. All the positive ones were bacterial, with no fungi. CONCLUSIONS:
      Transplant recipients were prone to develop bacterial rhinosinusitis by Gram
      positive and Gram negative agents, the most common of the latter being
      Pseudomonas aeruginosa. Fungal infections occurred in the severely
      immunosuppressed, and it was absent in immunocompetent patients.

PMID- 21860982
TI  - Bedside assessment of swallowing in elderly subjects using psychotropic drugs.
AB  - Neuroleptic drugs are used in several mental disorders, but are suspected of
      causing oropharyngeal dysphagia, mainly in the elderly. AIM: To study the effect
      of neuroleptic agents on swallowing of institutionalized older people. MATERIAL
      AND METHOD: A cross sectional study of swallowing in 47 subjects that either used
      or did not use neuroleptic drugs. Bedside swallowing tests with foods of four
      different consistencies were carried out. RESULTS: There was no significant
      difference between the two groups. Users of neuroleptic medications showed a
      higher percentage of multiple swallowing while non-users had a higher percentage
      of oral food escape. CONCLUSIONS: Neuroleptic agents alone do not affect the
      mechanism of swallowing in the elderly; nonetheless. Further studies with a
      larger number of individuals and specific swallowing tests are needed.

PMID- 21860983
TI  - TNF-R2 expression in acquired middle ear cholesteatoma.
AB  - Acquired middle ear cholesteatoma is a disease which promotes bone erosion
      resulting in potentially serious complications. The tumor necrosis factor alpha
      (TNF-alpha) is present in cholesteatoma and it is related to bone erosion, as
      shown by different authors. To understand the aggressiveness characteristics of
      cholesteatoma is necessary, however, to better address the presence and
      distribution of their receptors. OBJECTIVE: To evaluate the expression of type 2
      TNF-alpha receptor (TNF-R2) in fragments of cholesteatoma and correlate it to the
      degree of inflammation present. MATERIAL AND METHODS: observational cross
      sectional study, which analyzed 33 fragments of cholesteatomas through
      histological analysis and immunohistochemistry (using as primary antibody to TNF
      R2 LabVision(r) brand). The evaluation was performed by means of a qualitative
      and semi-quantitative agreement with the observed intensity. For statistical
      analysis we used the Fisher exact test and Spearman's correlation coefficient
      (considered statistically significant when p < 0. 05). RESULTS: The expression of
      TNF-R2 was present in all fragments, however a statistical analysis showed no
      correlation or association between inflammation and the expression of TNF-R2.
      CONCLUSIONS: TNF-R2 is present in cholesteatoma of the middle ear, however, its
      expression is not directly related to the degree of inflammation observed in
      patients with this disease.

PMID- 21860984
TI  - Obstructive sleep apnea: clinical results of a case treated with an oral
      appliance.

PMID- 21860985
TI  - Cochlear implant in type 2 neurofibromatosis: an option for better hearing
      rehabilitation.

PMID- 21860986
TI  - Bilateral antrochoanal polyps in an adult.

PMID- 21860987
TI  - Anterior laryngeal membrane and 22q11 deletion syndrome.

PMID- 21860988
TI  - Comparison between two different neuromuscular electrical stimulation protocols
      for the treatment of female stress urinary incontinence: a randomized controlled
      trial.
AB  - BACKGROUND: Neuromuscular electrical stimulation (NMES) is widely treatment for
      stress urinary incontinence (SUI) but there is no consensus in literature
      regarding the most effective treatment parameters. OBJECTIVE: To compare two
      NMESintra-vaginal protocols for the treatment of SUI in women. METHODS: The study
      included 20 volunteers with an average age of 55.55+/-6.51 years and with the
      clinical diagnosis of SUI. Volunteers were randomly divided into two groups:
      group 1 (G1) received NMES with medium-frequency current and group 2 (G2)
      received NMES with low-frequency current. Functional assessments of pelvic floor
      muscles (PFM) were performed by perineometry. The severity of signs and symptoms
      were objectively evaluated using the 1 hour pad test and subjectively evaluated
      using a visual analog scale that measured the discomfort caused by the SUI.
      Shapiro-Wilk test was used to analyze data normality, and the Friedman test was
      used to analyze nonparametric data. For analysis of symptoms related to SUI the
      Fisher exact test and the Mann-Whitney test were used. Significance level of 5%
      was set for all data analysis. RESULTS: No significant differences (p>0.05) were
      found between groups for any of the variable assessed. The within group analysis
      of initial and final evaluations (after NMES) demonstrated significant
      differences (p<0.05) in amount of urine lost, the discomfort caused by urinary
      incontinence and perineal pressure for both treatment groups. CONCLUSION: The two
      NMES protocols applied were equally effective in the treatment of SUI.

PMID- 21860989
TI  - Factorial analysis of the Multidimensional Health Locus of Control Scale--Form C
      for elderly.
AB  - BACKGROUND: Pain is a multidimensional experience. Locus of control is an
      important factor related to chronic pain experience and treatment. There is a gap
      in the literature when discussing issues related to pain evaluation in elderly.
      OBJECTIVES: To analyze the factorial structure, intra and inter-rater reliability
      of the Brazilian version of the Pain Locus of Control Scale - Form C for elderly
      with chronic pain living in the community. METHODS: One hundred and eighty one
      elderly individuals (71.5+/-6.8 years of age) answered a clinic and social
      demographic questionnaire and the PLOC-C scale. A factorial analysis with varimax
      rotation of the PLOC-C scale was performed. The scalewas applied twice by two
      observers to evaluate the intra and inter-rater reliability analyzed using
      Pearson's Correlation Coefficients. RESULTS: The factorial analysis of the 18
      item PLOC-C scale revealed six factors. Four items (1 and 6 from the chance locus
      of control subscale; 2 and 4 from the internal locus of control subscale)
      migrated toward unpredictable factors in the original factorial structure.
      Analysis with the removal of the four items demonstrated a better factorial
      structure and higher levels of internal consistency (alpha=0.836 and 0.669) and
      reliability (intra-examiner: r=0.65 and 0.93; inter-examiner: r=0.82 and 0.92)
      when compared to the complete subscales. The variance explained was of 48.7% for
      the 18 items and 62.4% for the 14 items scale. CONCLUSION: The results
      demonstrate a better applicability of the reduced scale on the sample. The
      reduced version may contribute to greater knowledge and consequently better
      chronic pain management in the elderly.

PMID- 21860990
TI  - Effect of pelvic floor muscle training on labour and newborn outcomes: a
      randomized controlled trial.
AB  - BACKGROUND: The use of the pelvic floor muscle training for urinary incontinence
      treatment is well established but little is known about its effects in labor and
      newborn outcomes. OBJECTIVES: To evaluate the effects of antenatal pelvic floor
      muscle training and strength in labor and newborn outcomes in low-income pregnant
      women. METHODS: This is a randomized controlled trial that recruited forty-two
      nulliparous healthy pregnant women aged between 18-36 years old and able to
      contract the pelvic floor muscles. The participants were included in the study
      with 20 weeks of gestational age and had their pelvic floor muscles measured by
      vaginal squeeze pressure. They were randomly allocated into two groups: training
      group and a non-intervention control group. Then, all participants had their
      labor and newborn outcomes evaluated through consultation of medical records by a
      blinded researcher. RESULTS: There were no statistically significant differences
      between the groups regarding gestational age at birth, type of labor, duration of
      the second stage of labor, total time of labor, prevalence of laceration, weight
      and size of the baby, and Apgar score. No correlation was observed between pelvic
      floor muscle strength and the second stage or the total length of labor.
      CONCLUSIONS: This randomized controlled trial did not find any effect of pelvic
      floor muscle training or pelvic floor muscle strength on labor and newborn
      outcomes.

PMID- 21860991
TI  - Functional and morphological changes in the quadriceps muscle induced by
      eccentric training after ACL reconstruction.
AB  - OBJECTIVES: The purpose of this study was to investigate the contributions of
      functional and morphological factors in the recovery of the quadriceps muscle
      after anterior cruciate ligament (ACL) reconstruction. METHODS: Nine subjects
      (31.3+/-5.8 years) underwent eccentric exercise sessions twice a week for 12
      weeks. Quadriceps muscle function was evaluated using an isokinetic dynamometer
      (isometric and eccentric peak torque) and electromyography (RMS). Morphological
      changes were measured using magnetic resonance imaging. RESULTS: The initial
      evaluation showed a significant deficit in knee extensor torque in the involved
      limb and significant muscle atrophy along the length of the quadriceps. EMG
      activity was lower in all tested situations. Eccentric training significantly
      increased isokinetic torque (from 199+/-51 to 240+/-63, p<0.05, respectively) and
      quadriceps area, with the greatest hypertrophy in the proximal thigh region (from
      169+/-27 to 189+/-25.8 cm2, p<0.01). The EMG activity of vastus medialis
      increased after the first six weeks of eccentric training. The increased extensor
      torque was correlated with quadriceps cross-sectional area (r=0.81, p<0.01) and
      EMG activity (r=0.69, p<0.05). After twelve weeks of training, there was a
      correlation only between torque and cross-sectional area (r=0.78, p<0.01).
      CONCLUSIONS: 1) eccentric training proved to be a potent resource for the
      quadriceps recovery, both morphologically and functionally, 2) the contributions
      of functional and morphological factors varied according to the length of
      training.

PMID- 21860992
TI  - Urinary incontinence and perineal muscle function in physically active and
      sedentary elderly women.
AB  - OBJECTIVE: To identify the presence of urinary incontinence and compare perineal
      muscle function among physically active and sedentary older women. METHODS: The
      sample consisted of 39 elderly women, 28 of whom got regular physical activity
      (AG) and 11 did not (SG). We collected data on risk factors for pelvic floor
      weakness and the presence of urinary incontinence (UI). The evaluation of
      perineal function was performed using PERFECT and perineometry. The data were
      processed with descriptive (simple frequencies, percentages, measures of position
      and dispersion) and inferential statistics (Chi-square or Fisher Exact Test, when
      necessary, and Mann-Whitney) with a significance level of 5%. RESULTS: There was
      a higher mean age (p=0.04) in AG. The occurrence of UI in the sample was 56.4%.
      Urge UI was associated with SG (p=0.022). All PERFECT variables were higher in AG
      than SG, with significant differences for the variables "repetitions" (p=0.008)
      and "fast" (p=0.022). Perineometry revealed that fast twitch fibers (p=0.008) and
      slow twitch fibers (p=0.05) were higher in the AG. CONCLUSION: AG had better
      pelvic floor muscle function. However, the prevalence of UI was higher in this
      group, which suggested the influence of age on the urinary continence mechanism.

PMID- 21860993
TI  - Comparison of capture methods for the diagnosis of adult anopheline populations
      from State of Mato Grosso, Brazil.
AB  - INTRODUCTION: The present study compares human landing catches of primary malaria
      vectors with two alternative methods of capture: the Shannon trap and the
      Mosquito magnet. METHODS: This study used regression models to adjust capture
      data to a negative binominal distribution. RESULTS: Capture numbers and relative
      percentages obtained from the three methods vary strongly between species. The
      highest overall captures were obtained for Anopheles triannulatus with captures
      for the Shannon trap and the Mosquito magnet measuring more than 330% higher than
      captures obtained by human landings. For Anopheles darlingi, captures by the
      Shannon trap and the Mosquito magnet were about 14% and 26% of human landing
      catches, respectively. Another species with malaria transmission potential that
      was not sampled by human landing captures weascaptured by the Shannon trap and
      the Mosquito magnet (Anopheles oswaldoi). Both alternative sampling techniques
      can predict the human landing of Anopheles triannulatus, but without
      proportionality. Models for Anopheles darlingi counts, after totaling daily
      captures, are significant and proportional, but prediction models are more
      reliable when using the Shannon trap compared with the Mosquito magnet captures.
      CONCLUSIONS: These alternative capture methods can be partially recommended for
      the substitution of human landing captures or, at least, as complementary forms
      of monitoring for malarial mosquitoes.

PMID- 21860994
TI  - Antimicrobial resistance of Shigella spp. isolated in the State of Para, Brazil.
AB  - INTRODUCTION: Shigella spp. are Gram-negative, nonsporulating, rod-shaped
      bacteria that belong to the family Enterobacteriaceae and are responsible for
      shigellosis or bacillary dysentery, an important cause of worldwide morbidity and
      mortality. METHODS: We studied the antibiotic resistance profiles of 122 Shigella
      spp. strains (81 S. flexneri, 41 S. sonnei, 1 S. boydii) isolated from patients
      (female and male from 0 to 80 years of age) presenting diarrhea in different
      districts of the State of Para, in the North of Brazil. The antibiotic resistance
      of the strains, isolated from human fecal samples, was determined by the
      diffusion disk method and by using the VITEK-2 system. RESULTS: The highest
      resistance rate found was the resistance rate to tetracycline (93.8%), followed
      by the resistance rate to chloramphenicol (63.9%) and to
      trimethoprim/sulfamethoxazole (63.1%). Resistance to at least three drugs was
      more common among S. flexneri than S. sonnei (39.5% vs. 10%). Six (4.9%) strains
      were susceptible to all the antibiotics tested. All strains were susceptible to
      cefotaxime, ceftazidime, ciprofloxacin, nalidixic acid and nitrofurantoin.
      CONCLUSIONS: High rates of multidrug resistance in Shigella spp. are a serious
      public health concern in Brazil. It is extremely important to continuously
      monitor the antimicrobial resistances of Shigella spp. for effective therapy and
      control measures against shigellosis.

PMID- 21860995
TI  - Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between
      1996 and 2009 in State of Rio de Janeiro, Brazil.
AB  - INTRODUCTION: Leptospirosis is a zoonotic disease found in tropical and temperate
      countries, and its clinical diagnostic confusion with arboviruses (dengue fever,
      oropouche fever and yellow fever), Brazilian spotted fever, viral hepatitis and
      hantaviruses has been an ongoing public health concern. The aim of this
      observational study was to demonstrate an association between findings of
      atypical lymphocytosis and the progression of endemic leptospirosis. METHODS: A
      retrospective analysis was performed on the demographic, epidemiological,
      clinical and laboratory aspects of 27 human leptospirosis cases that occurred
      over a period of 13 years (1996-2009) with no reported epidemic outbreaks in Rio
      de Janeiro, Brazil. RESULTS: The overall mortality rate was 11.1% in our cohort
      of hospitalized cases. However, there was no mortality among patients with
      atypical lymphocytosis (OR = 11.1; 95% CI = 1.12-110.9; p = 0.04). Two patients
      who were in the septicemic phase showed signs of expansion of gammadelta T cell
      responses in peripheral blood. CONCLUSIONS: Atypical lymphocytosis may be
      observed in patients with leptospirosis. Our observations suggest that these
      atypical leukocyte subsets are associated with partial protection during the
      disease course of leptospirosis.

PMID- 21860996
TI  - Evaluation of Leishmania (Leishmania) chagasi strains isolated from dogs
      originating from two visceral leishmaniasis-endemic areas in Brazil using
      multilocus enzyme electrophoresis.
AB  - INTRODUCTION: Domestic dogs are the most important reservoir in the peridomestic
      transmission cycle of Leishmania (Leishmania) chagasi. The genetic variability of
      subpopulations of this parasite circulating in dogs has not been thoroughly
      analyzed in Brazil, even though this knowledge has important implications in the
      clinical-epidemiological context. METHODS: The objective of this study was to
      evaluate and compare the phenotypic variability of 153 L. chagasi strains
      isolated from dogs originating from the municipalities of Rio de Janeiro (n = 57)
      and Belo Horizonte (n = 96), where the disease is endemic. Strains isolated only
      from intact skin were selected and analyzed by multilocus enzyme electrophoresis
      using nine enzyme systems (6PG, GPI, NH1 and NH2, G6P, PGM, MDH, ME, and
      IDHNADP). RESULTS: The electrophoretic profile was identical for all isolates
      analyzed and was the same as that of the L. chagasi reference strain
      (MHOM/BR/74/PP75). Phenetic analysis showed a similarity index of one for all
      strains, with the isolates sharing 100% of the characteristics analyzed.
      CONCLUSIONS: The results demonstrate that the L. chagasi populations circulating
      in dogs from Rio de Janeiro and Belo Horizonte belong to a single zymodeme.

PMID- 21860997
TI  - Restriction enzyme analysis of the human cytomegalovirus genome in specimens
      collected from immunodeficient patients in Belem, State of Para, Brazil.
AB  - INTRODUCTION: Human cytomegalovirus is an opportunistic betaherpesvirus that
      causes persistent and serious infections in immunodeficient patients. Recurrent
      infections occur due to the presence of the virus in a latent state in some cell
      types. It is possible to examine the virus using molecular methods to aid in the
      immunological diagnosis and to generate a molecular viral profile in
      immunodeficient patients. The objective of this study was to characterize
      cytomegalovirus genotypes and to generate the epidemiological and molecular viral
      profile in immunodeficient patients. METHODS: A total of 105 samples were
      collected from immunodeficient patients from the City of Belem, including
      newborns, hemodialysis patients, transplant recipients and HIV+ patients. An IgG
      and IgM antibody study was completed using ELISA, and enzymatic analysis by
      restriction fragment length polymorphism (RFLP) was performed to characterize
      viral genotypes. RESULTS: It was observed that 100% of the patients had IgG
      antibodies, 87% of which were IgG+/IgM-, consistent with a prior infection
      profile, 13% were IgG+/IgM+, suggestive of recent infection. The newborn group
      had the highest frequency (27%) of the IgG+/IgM+ profile. By RFLP analysis, only
      one genotype was observed, gB2, which corresponded to the standard AD169 strain.
      CONCLUSIONS: The presence of IgM antibodies in new borns indicates that HCMV
      continues to be an important cause of congenital infection. The low observed
      genotypic diversity could be attributed to the small sample size because newborns
      were excluded from the RFLP analysis. This study will be continued including
      samples from newborns to extend the knowledge of the general and molecular
      epidemiology of HCMV in immunodeficient patients.

PMID- 21860998
TI  - Biofilm production using distinct media and antimicrobial susceptibility profile
      of Pseudomonas aeruginosa.
AB  - Biofilm production is an important mechanism for bacterial survival and its
      occurrence together with antimicrobial resistance represents a challenge for
      clinical management. Here, we evaluated the ability for biofilm production among
      P. aeruginosa isolates from patients with or without cystic fibrosis (CF) using
      two distinct media, besides determining the antimicrobial susceptibility profile
      of these isolates for eight antimicrobial agents. The ability for biofilm
      production when TSB medium was used was higher than when used CF sputum media (p
      = 0.0198). However, P. aeruginosa isolates from CF have demonstrated similar
      performance for biofilm production, independently of the medium used. Besides,
      among the biofilm-producing isolates, those recovered from CF were more resistant
      to the carbapenems (meropenem and imipenem) agents than those isolates from non
      CF isolates.

PMID- 21860999
TI  - Evaluation of different detection methods of biofilm formation in the clinical
      isolates.
AB  - BACKGROUND: Microorganisms growing in a biofilm are associated with chronic and
      recurrent human infections and are highly resistant to antimicrobial agents.
      There are various methods to detect biofilm production like Tissue Culture Plate
      (TCP), Tube method (TM), Congo Red Agar method (CRA), bioluminescent assay,
      piezoelectric sensors, and fluorescent microscopic examination. OBJECTIVE: This
      study was conducted to compare three methods for the detection of biofilms.
      METHOD: The study was carried out at the Department of Microbiology, Army Medical
      College, National University of Sciences and Technology, Pakistan, from January
      2010 to June 2010. A total of 110 clinical isolates were subjected to biofilm
      detection methods. Isolates were identified by standard microbiological
      procedures. Biofilm detection was tested by TCP, TM and CRA. Antibiotic
      susceptibility test of biofilm producing bacteria was performed by using the
      Kirby-Bauer disc diffusion technique according to CLSI guidelines. RESULTS: The
      TCP method was considered to be superior to TM and CRA. From the total of 110
      clinical isolates, TCP method detected 22.7% as high, 41% moderate and 36.3% as
      weak or non-biofilm producers. We have observed higher antibiotic resistance in
      biofilm producing bacteria than non-biofilm producers. CONCLUSION: We can
      conclude from our study that the TCP method is a more quantitative and reliable
      method for the detection of biofilm forming microorganisms as compared to TM and
      CRA methods, and it can be recommended as a general screening method for
      detection of biofilm producing bacteria in laboratories.

PMID- 21861000
TI  - Outbreaks, persistence, and high mortality rates of multiresistant Pseudomonas
      aeruginosa infections in a hospital with AIDS-predominant admissions.
AB  - INTRODUCTION: Authors have reported increased incidence of multiresistant
      Pseudomonas aeruginosa (MR-PA) infections worldwide over the last decade.
      Researchers have proposed multifaceted approaches to control MR-PA infections,
      but none have been reported in the acquired immunodeficiency syndrome (AIDS)
      setting. OBJECTIVE AND METHODS: Herein we report the impact of a multifaceted
      intervention for controlling MR-PA over five years in a hospital with AIDS
      predominant admissions and describe the clinical characteristics of MR-PA
      infection in our patient population. The clinical outcomes of infected patients
      and molecular characteristics of the isolated strains were used as tools for
      controlling MR-PA infection rates. RESULTS: Significant temporary decrease of new
      infections was achieved after intervention, although a high level of diagnostic
      suspicion of nosocomial infection was maintained. We obtained 35 P. aeruginosa
      isolates with multiresistant profiles from 13 infected and 3 colonized patients
      and 2 environmental samples. Most of the patients (94%) were immunocompromised
      with AIDS (n = 10) or HTLV-1 infections (n = 5). Of the followed patients, 67%
      had persistent and/or recurrent infections, and 92% died. We observed differences
      in the antibiotic-resistance pattern of MR-PA infection/colonization during two
      outbreaks, although the genetic profiles of the tested strains were identical.
      CONCLUSIONS: Therefore, we concluded that early multidisciplinary interventions
      are essential for reducing the burden caused by this microorganism in patients
      with AIDS. Prolonged or suppressive antibiotic-based therapy should be considered
      for MR-PA infections in patients with AIDS because of the persistence
      characteristic of MR-PA in these patients.

PMID- 21861001
TI  - Group B Streptococcus detection: comparison of PCR assay and culture as a
      screening method for pregnant women.
AB  - Streptococcus agalactiae or group B Streptococcus (GBS) is one of the most
      important causal agents of serious neonatal infections. Numerous assays have been
      evaluated for GBS screening in order to validate a fast and efficient method. The
      aim of this study was to compare the culture technique (established as the gold
      standard) with the molecular method of polymerase chain reaction (PCR) with
      specific primers (atr gene). Two hundred and sixty-three samples were analyzed.
      Vaginal samples were collected, according to the Centers for Disease Control and
      Prevention (CDC) recommendations, from women over 35 weeks of pregnancy at
      Hospital de Clinicas de Porto Alegre (HCPA). Two different extraction methods
      were tested in all samples collected. PCR technique yielded 71 (26.99%) positive
      results. Sensitivity and specificity for PCR were 100% and 86.88%, respectively.
      PCR demonstrated a shorter turnaround time than the culture. The molecular
      methodology proved to be a useful screening for GBS, allowing effective treatment
      to be initiated in shorter time to prevent newborn infection.

PMID- 21861002
TI  - Risk factors for catheter-related bloodstream infection: a prospective
      multicenter study in Brazilian intensive care units.
AB  - INTRODUCTION: Central venous catheters (CVC) are devices of great importance in
      health care. The advantages gained from the use of catheters outweigh the
      complications that might result from their use, among which bloodstream
      infections (BSI). In spite of its importance, few national studies have addressed
      this issue. OBJECTIVE: The aim this study was to determine the incidence of BSI
      in patients with CVC, hospitalized in ICU, as well as the variables associated
      with this complication. METHODS: Multicentric cohort study carried out at ICUs of
      three hospitals at Universidade Federal de Sao Paulo complex. RESULTS: A total of
      118 cases of BSI in 11.546 catheters day were observed: 10.22 BSI per 1,000
      catheters day. On average, BSI was associated to seven additional days of
      hospital stay in our study (p < 0.001), with a significant difference between
      types of catheters. Concerning the place of insertion, there was no statistical
      difference in BSI rates. CONCLUSION: We concluded that a patient who uses a
      catheter for longer than 13 days presents a progressive risk for infection of
      approximately three times higher in relation to a patient who uses the catheter
      for less than 13 days (p < 0.001). The median duration of catheter use was 14
      days among patients with BSI and 9 days in patients without infection (p <
      0.001). There was higher prevalence of gram-negative infections. The risk factors
      for BSI were utilization of multiple-lumen catheters, duration of catheterization
      and ICU length of stay.

PMID- 21861003
TI  - Propolis derivatives inhibit the systemic inflammatory response and protect
      hepatic and neuronal cells in acute septic shock.
AB  - BACKGROUND: Severe pathogenic infection triggers excessive release of cytokines
      as part of the massive inflammatory response associated with septic shock.
      OBJECTIVES: To investigate the protective effect of caffeic acid phenethyl ester
      (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal
      damage and the associated systemic inflammatory response (SIR). METHODS: Fifty
      male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma
      concentrations of various cytokines, including TNF-alpha, IL-1alpha, IL-1beta, IL
      6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological
      changes in the hepatic and neural cells were assessed. RESULTS: The LPS group
      showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of
      SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory
      cellular infiltration together with brain astrocytes swelling, early neuron
      injury and presence of inflammatory foci confirmed the toxic tissue damage. Use
      of CAPE decreased the inflammatory cytokines and increased the anti-inflammatory
      cytokines levels. This biochemical evidence of decreased SIR was confirmed
      histologically by decreased cellular infiltration in the liver and brain tissue
      which coincides with preserved structure and protection of the liver and brain
      cells from the toxic effects of LPS. CONCLUSION: The ability of CAPE to alleviate
      the SIR, hepatic and neuronal cell damage induced by LPS and galactosamine could
      be attributed to its ability to reverse the imbalance of the pro- and anti
      inflammatory cytokines which may lead to the inhibition of adhesion molecules'
      expression. CAPE is a promising agent that could help in the prophylaxis and
      treatment of septic shock.

PMID- 21861004
TI  - Antimicrobial activity of ceftobiprole against gram-negative and gram-positive
      pathogens: results from INVITA-A-CEFTO Brazilian study.
AB  - Ceftobiprole is a broad-spectrum cephalosporin with potent activity against
      staphylococci, including those resistant to oxacillin, as well as against most
      gram-negative bacilli including Pseudomonas aeruginosa. In this study, the in
      vitro activity of ceftobiprole and comparator agents was tested against bacterial
      isolates recently collected from Brazilian private hospitals. A total of 336
      unique bacterial isolates were collected from hospitalized patients between
      February 2008 and August 2009. Each hospital was asked to submit 100 single
      bacterial isolates responsible for causing blood, lower respiratory tract or skin
      and soft tissue infections. Bacterial identification was confirmed and
      antimicrobial susceptibility testing was performed using CLSI microdilution
      method at a central laboratory. The CLSI M100-S21 (2011) was used for
      interpretation of the antimicrobial susceptibility results. Among the 336
      pathogens collected, 255 (75.9%) were gram-negative bacilli and 81 (24.1%) were
      gram-positive cocci. Although ceftobiprole MIC50 values for oxacillin resistant
      strains were two-fold higher than for methicillin susceptible S. aureus,
      ceftobiprole inhibited 100% of tested S. aureus at MICs < 4 ug/mL. Polymyxin B
      was the only agent to show potent activity against Acinetobacter spp. (MIC50/90,
      0.5/1 ug/mL), and P. aeruginosa (MIC50/90, 1/2 ug/mL). Resistance to broad
      spectrum cephalosporins varied from 55.3-68.5% and 14.3-28.5% among E. coli and
      Klebsiella spp. isolates, respectively; with ceftobiprole MIC50 > 6 ug/mL for
      both species. Our results showed that ceftobiprole has potent activity against
      staphylococci and E. faecalis, which was superior to that of vancomycin. Our data
      also indicates that ceftobiprole demonstrated potency comparable to that of
      cefepime and ceftazidime against key gram-negative species.

PMID- 21861005
TI  - Epidemiologic and clinical characteristics of pregnant women living with HIV/AIDS
      in a region of Southern Brazil where the subtype C of HIV-1 infection
      predominates.
AB  - Southern Brazil has the highest prevalence rate of AIDS in the country and is the
      only region in the Americas where HIV-1 subtype C prevails. OBJECTIVE: We
      evaluated the epidemiologic and clinical characteristics of pregnant women living
      with HIV/AIDS in the South region of Santa Catarina, Brazil. METHODS: All
      pregnant women with HIV infection attending the obstetric outpatient clinic of
      Criciuma, State of Santa Catarina, in 2007 (n = 46) were invited to participate.
      Data of 36 eligible participants were obtained through a standardized
      questionnaire. RESULTS: The great majority were young, with a steady partner, low
      family income, low education level and referring early first sexual intercourse.
      Many reported use of illicit non-injecting drugs (55.5%) and unprotected sex with
      partners that were HIV-positive (57.7%), injecting drug user (22.2%), male inmate
      (19.4%), truck driver (13.8%), with history of sexually transmitted disease
      (11.1%) or men who have sex with men (MSM) (2.8%). Most (66.7%) of the
      participants had their HIV diagnosis done during the pregnancy, 7 (19.4%) had a
      previous history of HIV mother-to-child transmission. Therapy based on highly
      active antiretroviral therapy (94%) was initiated at 19.3 weeks on average and
      33% showed irregular antiretroviral adherence. CONCLUSION: These results confirm
      previous data on HIV epidemiology in Brazil and suggest that the women partners'
      sexual behavior and unprotected sexual intercourse are important aspects of HIV
      epidemic. Additional efforts in education, prophylaxis and medication adherence
      are needed.

PMID- 21861006
TI  - Importance of high IgG anti-Toxoplasma gondii titers and PCR detection of T.
      gondii DNA in peripheral blood samples for the diagnosis of AIDS-related cerebral
      toxoplasmosis: a case-control study.
AB  - BACKGROUND: Cerebral toxoplasmosis (CT) continues to cause significant morbidity
      and mortality in human immunodeficiency virus (HIV)-infected patients in Brazil.
      In clinical practice, the initial diagnosis is usually presumptive and
      alternative diagnosis tools are necessary. Our objective was to evaluate whether
      the detection of high titers of IgG anti-Toxoplasma gondii and T. gondii DNA in
      blood samples are associated with the diagnosis of CT. METHODS: In this case
      control study we included 192 patients with HIV-1 infection: 64 patients with
      presumptive CT (cases) and 128 patients with other diseases (controls). Blood
      samples to perform indirect immunofluorescense reaction (IFI) to detect anti-T.
      gondii IgG antibodies and polymerase chain reaction (PCR) were collected before
      or within the first three days of anti-Toxoplasma therapy. Two multivariate
      logistic regression models were performed: one including the variable qualitative
      serology and another including quantitative serology. RESULTS: In the first
      model, positive IgG anti-T. gondii (OR 4.7, 95% CI 1.2-18.3; p = 0.027) and a
      positive T. gondii PCR result (OR 132, 95% CI 35-505; p < 0.001) were associated
      with the diagnosis. In the second model, IgG anti-T. gondii titres > 1:1024 (OR
      7.6, 95% CI 2.3-25.1; p = 0.001) and a positive T. gondii PCR result (OR 147, 95%
      CI 35-613; p < 0.001) were associated with the diagnosis. CONCLUSIONS:
      Quantitative serology and molecular diagnosis in peripheral blood samples were
      independently associated with the diagnosis of CT in HIV-infected patients. These
      diagnostic tools can contribute to a timely diagnosis of CT in settings where
      Toxoplasma infection is common in the general population.

PMID- 21861007
TI  - Behavioral and biological risks of women seeking HIV test in an anonymous testing
      center.
AB  - Due to the high prevalence and morbidity sexually transmitted diseases are highly
      relevant to public health, especially for women. OBJECTIVES: To determine and
      compare the behavioral and biological risks associated with human
      immunodeficiency virus acquisition. METHODS: A group of 253 women who voluntarily
      sought anonymous testing were interviewed to find out their behavioral risk.
      Biological risk was identified by means of gynecological exam, colposcopy as well
      as blood and cervicovaginal sampling for serological and microbiological exams.
      Using known traditional risk factors, a table of scores classified the subjects
      into high, low and absent for behavioral and biological risks. Frequency and
      percentage of each risk was tabulated and the correlation between risks was
      obtained by calculating the Kappa statistic. RESULTS: 79.8% of subjects were
      found to have behavioral risks, and 79.1% biological risks. It was also found
      that 66.7% of the women (169) with high behavioral risk also had high biological
      vulnerability. However, 31 out of 51 women without any behavioral risk had
      biological vulnerability 12.2 %. The Kappa statistic demonstrated low agreement
      between the latter risks [K = 0.05 95% CI (-0.06 to 0.17)]. CONCLUSION: Women who
      seek care in centers for anonymous testing have high biological risk, which is
      neither proportional nor concurrent to behavioral risk. The low concordance found
      between these risks suggests the need for routine gynecological investigation
      (clinical and microbiological) for all women.

PMID- 21861008
TI  - Comparison of multiplex PCR with serogrouping and PCR-RFLP of fliC gene for the
      detection of enteropathogenic Escherichia coli (EPEC).
AB  - Enteropathogenic Escherichia coli (EPEC) comprise one of the six categories of
      diarrhoeagenic E. coli (DEC). EPEC is subgrouped into typical (tEPEC) and
      atypical (aEPEC). The identification of DEC cannot be based only on cultural and
      biochemical criteria, since they are indistinguishable from the non-pathogenic E.
      coli commonly found in human feces. Several PCR methods, with both single and
      multiple target genes, have been reported for detecting the different DEC
      pathotypes. In the present study five hundred E. coli isolates from children with
      diarrhea were subjected into multiplex PCR. Furthermore the strains were typed
      serologically with O antisera and their fliC gene was characterized by PCR-RFLP.
      The results obtained revealed that overall 41 (8.2%) isolates could be detected
      as EPEC by this multiplex PCR assay. Of these isolates; 27 (66%) were typical
      (escv+, bfp+) and 14 (34%) atypical EPEC (escv+, bfp-). None of these 41 isolates
      contained the Stx1 and Stx2 genes. Among 37 (90%) typeable strains, nine
      different serogroups were present. The most common serogroups were O111, followed
      by O86, O55 and O119 and 10 different H types were found among these isolates.
      The multiplex PCR assay was found to be rapid and reliable in comparison to
      serological test; especially when screening the large number of isolates.

PMID- 21861009
TI  - Risk factors for bloodstream infections caused by extended-spectrum beta
      lactamase-producing Escherichia coli and Klebsiella pneumoniae.
AB  - The objective of this study was to identify risk factors for bacteremia by
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella
      pneumoniae. Retrospective case-control study performed in a 450-bed acute care
      academic tertiary hospital in Barcelona, Spain. Cases included 53 patients with
      ESBL-producing E. coli or K. pneumoniae bacteremia, and 159 controls with non
      ESBL-producing E. coli or K. pneumoniae bacteremia. Controls were matched in a
      3:1 ratio to case patients according to species of infecting organism, age, and
      severity of illness in the 24-48 h before blood sample collection for culture
      calculated by the Simplified Acute Physiology Score (SAPS II) system. Previous
      antimicrobials were more frequently administered to cases than to controls (56.5%
      vs 17%, p < 0.001). Binary logistic regression showed that the number (> 2) of
      different families of antimicrobials received within 90 days before bloodstream
      infection was the only predictor of ESBL-producing E. coli or K. pneumoniae in
      blood culture (OR = 2.29, 95% CI 1.35-3.88, p = 0.002). CONCLUSION: Previous use
      of different families of antimicrobials (more than two) in patients with
      bloodstream infection caused by E. coli or K. pneumoniae increased the risk for
      ESBL-producing strains.

PMID- 21861010
TI  - Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and
      ribavirin therapy.
AB  - OBJECTIVE: To investigate the frequency of thyroid disorders (TD) in patients
      with chronic hepatitis C before and during interferon-alpha (IFN-alpha) and
      ribavirin (RIB) treatment. STUDY DESIGN: Prospective study. PATIENTS AND METHODS:
      We prospectively studied 65 anti-HCV and viral RNA positive patients. Free
      thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO
      Ab) were systematically tested at entry (m0), week 12 (m3) and week 24 (m6) of
      treatment. RESULTS: Mean age of the 65 patients (38 females and 27 males) was
      49.61 +/- 11.83 years. Seven (10.76%) patients presented baseline thyroid
      disorders (m0), three had thyroid dysfunction, and four were TPO-Ab positive.
      Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92%)
      patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3). A
      total of 18 patients (27.69%) developed TD after 24 weeks of treatment, 7 with
      thyroid dysfunction, and 11 with TPO-Ab positive (m6). The relative risk of
      developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6),
      hyperthyroidism 1.2 (95% CI: 1.1 to 1.4), and TPO-Ab positivity 7.6 (95% CI: 3.9
      to 14.5). The study showed a significant association between female sex and
      thyroid disease (p = 0.009). CONCLUSION: Thyroid dysfunction and autoimmune TD
      were observed during IFN-alpha and RIB therapy.

PMID- 21861011
TI  - Giardiasis as zoonosis: between proof of principle and paradigm in the
      Northwestern region of Sao Paulo State, Brazil.
AB  - OBJECTIVE: In order to evaluate the potential zoonotic transmission of Giardia
      duodenalis, isolates from humans and dogs in the Northwestern region of the Sao
      Paulo State, Brazil were characterized based on the beta-giardin gene. METHODS:
      The samples were analyzed by sequencing of the Nested-PCR products. RESULTS: The
      A1 and A2 subgenotypes were detected in human and dogs. Cysts of assemblage B, C
      and D have not been found in any isolates studied. CONCLUSIONS: These results are
      consistent with the view that giardiasis in the largest endemic region of the
      Brazil should not be seen as a single entity.

PMID- 21861012
TI  - Infectious endocarditis caused by Nocardia sp.: histological morphology as a
      guide for the specific diagnosis.
AB  - Nocardia is a rare opportunistic agent, which may affect immunocompromised
      individuals causing lung infections and exceptionally infective endocarditis
      (IE). There are few reports of IE caused by Nocardia sp., usually involving
      biological prostheses but rarely in natural valves. Its accurate microbiological
      identification may be hampered by the similarity with Rhodococcus equi and
      Corynebacterium spp. Here we report a case of native mitral valve IE caused by
      this agent in which the clinical absence of response to vancomycin and the
      suggestion of Nocardia sp. by histology pointed to the misdiagnosis of
      Corynebacterium spp. in blood cultures. The histological morphology can advise on
      the need for expansion of cultivation time and use of extra microbiological
      procedures that lead to the differential diagnosis with Corynebacterium spp. and
      other agents, which is essential to establish timely specific treatment,
      especially in immunocompromised patients.

PMID- 21861013
TI  - Breast cancer in a cohort of human immunodeficiency virus (HIV)-infected women
      from Rio de Janeiro, Brazil: a cases series report and an incidence rate
      estimate.
AB  - Highly active antiretroviral therapy (HAART) has changed the morbidity pattern
      affecting HIV-infected individuals to include non-AIDS-defining cancers. We
      describe the breast cancer cases occurring in a cohort of 860 HIV-infected women
      followed in Rio de Janeiro, Brazil, and estimate the incidence rate of breast
      cancer for this population. Nine cases were identified; median age at diagnosis
      was 46 years. Median survival after breast cancer diagnosis was 12 months. Breast
      cancer diagnosis was made within 2 to 15 years of HIV-infection diagnosis. At
      breast cancer diagnosis, CD4 counts ranged from 135 to 782 cells/mm3; six women
      were receiving HAART. Histological analysis indicated infiltrating ductal
      carcinoma in all cases. The incidence rate of breast cancer was 133 cases per
      100,000 persons-year. Patients from our case series were late diagnosed with
      breast cancer and thus suffered from worse prognosis. Strategies targeting
      earlier diagnosis and prompt initiation of treatment are needed.

PMID- 21861014
TI  - Multiple cutaneous swellings in an immunocompetent host--cryptococcosis
      overlooked.
AB  - Recently, there has been an increase in the incidence of cryptococcosis even
      among immunocompetent patients. We present a case of multiple subcutaneous
      swellings later developing into a non-healing ulcer caused by Cryptococcus in a
      60 year-old immunocompetent male along with a brief review of clinical
      presentations of cutaneous cryptococcosis in immunocompetent and
      immunocompromised individuals. A high index of suspicion is desired in view of
      possible dissemination and variable non-specific clinical presentations.

PMID- 21861015
TI  - Use of assisted reproductive technology to separate sperm from human
      immunodeficiency virus infected men resulting in pregnancy among serodiscordant
      couples.
AB  - Due to HIV care improvement, discordant couples more frequently seek help in
      order to conceive their own biological child. Besides the advance of
      antiretroviral therapy, unprotected intercourse is not a complete safe option,
      carrying a low but still present risk of HIV transmission. We report 10
      serodiscordant couples in whom the male partner is HIV positive, submitted to
      sperm washing and intrauterine insemination. The procedure resulted in four
      pregnancies and no HIV transmission to mother or child was observed. Techniques
      of assisted reproduction can help HIV discordant couples to conceive biological
      offspring and is a safer option than unprotected intercourse.

PMID- 21861016
TI  - Cryptococcal meningitis in HIV-negative patient with liver cirrhosis due to
      hepatitis C.

PMID- 21861017
TI  - Invasive bacteria isolates from children with cerebral shunt and pattern of
      antimicrobial drug susceptibility in an Iranian referral pediatrics center.

PMID- 21861018
TI  - Outbreak of vancomycin-resistant Enterococcus in a renal transplant unit.

PMID- 21861019
TI  - Unusual clinical presentations of brucellosis in childhood.

PMID- 21861020
TI  - Bacteremia among liver and kidney transplant recipients: etiologic agents and
      antimicrobial susceptibilities.

PMID- 21861021
TI  - Comment on: "Effect of sustained virologic response on the incidence of
      hepatocellular carcinoma in patients with HCV cirrhosis".

PMID- 21861022
TI  - Clinical aspects of pediatric AIDS cases notified in the state of Amazonas, 1991
      2009.

PMID- 21861023
TI  - Genotypic and phenotypic analysis of S. mutans isolated from dental biofilms
      formed in vivo under high cariogenic conditions.
AB  - The oral cavity harbors several Streptococcus mutans genotypes, which could
      present distinct virulence properties. However, little is known about the
      diversity and virulence traits of S. mutans genotypes isolated in vivo under
      controlled conditions of high cariogenic challenge. This study evaluated the
      genotypic diversity of S. mutans isolated from dental biofilms formed in vivo
      under sucrose exposure, as well as their acidogenicity and aciduricity. To form
      biofilms, subjects rinsed their mouths with distilled water or sucrose solution 8
      times/day for 3 days. S. mutans collected from saliva and biofilms were genotyped
      by arbitrarily-primed PCR. Genotypes identified in the biofilms were evaluated
      regarding their ability to lower the suspension pH through glycolysis and their
      acid susceptibility and F-ATPase activity. Most subjects harbored only one
      genotype in saliva, which was detected in almost all biofilm samples at high
      proportions. Genotypes isolated only in the presence of sucrose had higher
      acidogenicity than those isolated only in the presence of water. Genotypes from
      biofilms formed with sucrose were more aciduric after 30 and 60 min of incubation
      at pH 2.8 and 5.0, respectively. The present results suggest that biofilms formed
      under high cariogenic conditions may harbor more aciduric and acidogenic S.
      mutans genotypes.

PMID- 21861024
TI  - Fluoride release profile of a nanofilled resin-modified glass ionomer cement.
AB  - The present study aimed to compare the fluoride (F-) release pattern of a
      nanofilled resin-modified glass ionomer cement (GIC) (Ketac N100 - KN) with
      available GICs used in dental practice (resin-modified GIC - Vitremer - V;
      conventional GIC - Ketac Molar - KM) and a nanofilled resin composite (Filtek
      Supreme - RC). Discs of each material (n=6) were placed into 4 mL of deionized
      water in sealed polyethylene vials and shaken, for 15 days. F- release (MUg F
      /cm2) was measured each day using a fluoride-ion specific electrode. Cumulative F
      release means were statistically analyzed by linear regression analysis. In
      order to analyze the differences among materials and the influence of time in the
      daily F- release, 2-way ANOVA test was performed (alpha=0.05). The linear fits
      between the cumulative F- release profiles of RC and KM and time were weak. KN
      and V presented a strong relationship between cumulative F- release and time.
      There were significant differences between the daily F- release overtime up to
      the third day only for GICs materials. The daily F- release means for RC were
      similar overtime. The results indicate that the F- release profile of the
      nanofilled resin-modified GIC is comparable to the resin-modified GIC.

PMID- 21861025
TI  - Effects of oral environment stabilization procedures on Streptococcus mutans
      counts in pregnant women.
AB  - The aim of this study was to determine the effect of oral environment
      stabilization (OES) on the counting of Streptococcus mutans in high-caries-risk
      pregnant women participants of a prevention program in a public teaching
      institution. The sample was composed of 30 pregnant women aged 18 to 43 years,
      who looked for treatment at the Preventive Dentistry Clinic of the Araraquara
      Dental School, UNESP. Saliva samples were collected before and after the OES
      procedures and were forwarded to the pathology for observation and quantification
      of S. mutans CFU. There was a decrease in the number of S. mutans CFU, which was
      significantly different (p<0.0001) between samples. Considering the age group,
      70.0% were between 18 to 30 years old and 30.0% belonged to the 31-43-year-old
      age group. Data related to the pregnancy period showed that 73.4% were in the
      second trimester, 13.3% in the first and 13.3% in third trimester. OES showed to
      be an effective clinical procedure in diminishing the number of S. mutans CFU in
      the saliva of high-caries-risk pregnant women. This management is simple and
      effective, corresponding to the basic treatment needs of pregnant women that
      search dental care in this public service.

PMID- 21861026
TI  - Antibacterial effectiveness of peracetic acid and conventional endodontic
      irrigants.
AB  - This study evaluated the in vitro antibacterial activity of conventional and
      experimental endodontic irrigants against Enterococcus faecalis. The following
      substances were evaluated by direct contact test: 2.5% sodium hypochlorite
      (NaOCl); 2% chlorhexidine (CHX); 1% peracetic acid. After different contact
      periods (30 s, 1, 3, and 10 min), a neutralizing agent was applied. Serial 10
      fold dilutions were prepared and plated onto tryptic soy agar (TSA) and the
      number of colony-forming units per milliliter (CFU/mL) was determined. Sterile
      saline was used as a negative control. Both 2.5% NaOCl and 2% CHX eliminated E.
      faecalis after 30 s of contact. Peracetic acid reduced the bacterial counts by
      86% after 3 min and completely eliminated E. faecalis after 10 min. These results
      allow us to conclude that 1% peracetic acid is effective against E. faecalis,
      despite its slower action compared with 2.5% NaOCl and 2% CHX.

PMID- 21861027
TI  - CT evaluation of apical canal transportation associated with stainless steel hand
      files, oscillatory technique and pro taper rotary system.
AB  - This study used computed tomography (CT) to compare apical canal transportation
      in mesiobuccal canals of maxillary molars prepared with different techniques.
      Sixty teeth were assigned to 3 groups (n=20), according to the technique used for
      root canal instrumentation: hand instrumentation with K-Flexofiles, K-Flexofiles
      activated by an oscillatory system and ProTaper NiTi rotary system. Pre and post
      instrumentation CT images were obtained 3 mm short of the apical foramen and were
      superimposed to compare canal transportation. Data were analyzed statistically by
      ANOVA and Tukey's test using the SPSS software (alpha=0.05). In the buccal
      direction, the manual technique produced significantly less canal transportation
      than the oscillatory technique (p<0.05) and both were similar to the rotary
      technique (p>0.05). In the distal and distopalatal directions, the oscillatory
      technique produced more canal transportation (p<0.05). In the mesiopalatal
      direction, the oscillatory technique produced more canal transportation than the
      manual technique (p<0.05), and both were similar to the rotary technique
      (p>0.05). In conclusion, all techniques produced canal transportation, and the
      oscillatory technique produced the greatest removal of root dentin toward the
      innerside of the root curvature.

PMID- 21861028
TI  - Efficacy of five rotary systems versus manual instrumentation during endodontic
      retreatment.
AB  - The purpose of this study was to evaluate the efficiency of ProFile, GT,
      ProTaper, Race and K3 rotary instruments compared with hand K-files for removal
      of gutta-percha during retreatment. Sixty mandibular premolars were instrumented
      with GT rotary files and filled by thermomechanical compaction of gutta-percha
      and AH Plus sealer. The teeth are randomly divided into 6 groups of 10 specimens
      each. The roots were split longitudinally, digital images were created using a
      flatbed scanner, and the areas with remaining filling material were demarcated
      using Image Tool 1.21 software. The results indicate that GT left significantly
      less (p<0.05) remaining filling material (1.18 +/- 1.47) than hand (3.70 +/-
      3.16) and Hero instruments (2.99 +/- 2.58). There was no statistically
      significant difference (p<0.05) among the others techniques: ProFile (1.99 +/-
      2.66), ProTaper (2.00 +/- 1.99) and K3 (2.71 +/- 2.87) when compared with GT. In
      conclusion, GT, ProFile, ProTaper and K3 were more effective in removing gutta
      percha than manual and Hero instruments.

PMID- 21861029
TI  - Biocompatibility of sealers used in apical surgery: a histological study in rat
      subcutaneous tissue.
AB  - The aim of this study was to evaluate the biocompatibility of sealers used in
      apical surgery in rat subcutaneous tissue. Sterile polyethylene tubes were filled
      with the following sealers: Sealapex, Sealapex with addition of zinc oxide,
      Sealer 26, Sealer 26 with thicker consistency (greater powder-to-resin ratio) and
      White MTA. The tubes were implanted in the dorsum of male rats and after 7, 21
      and 42 days, the animals were killed, obtaining 5 specimens for each sealer in
      each evaluation period. The lateral surface of the tube was used as negative
      control. The inflammatory reaction to contact with the sealers was classified as
      absent, mild, moderate and severe. At 7 days, all sealers caused similar
      inflammatory reactions in the connective tissue of the animals, with most
      specimens presenting a moderate to intense chronic inflammatory reaction, with
      presence of multinucleated giant cells. At 21 days, Sealer 26 and Sealer 26 with
      thicker consistency presented more intense inflammatory reaction (p=0.004),
      whereas after 42 days, the inflammatory reaction ranged from absent to mild with
      statistically similar results for both materials (p=0.08). Except for MTA, all
      sealers presented foreign-body granulomatous reaction at 42 days. All sealers but
      Sealapex presented a statistically significant decrease of the inflammatory
      reaction over time. In conclusion, all sealers caused moderate to severe
      inflammation in the earlier evaluation period. However, Sealer 26 and Sealer 26
      with thicker consistency caused more intense inflammatory reactions after 21 days
      of contact with the tissues and no granulomatous reaction was observed for MTA at
      the final period of analysis.

PMID- 21861030
TI  - Diagnostic and clinical factors associated with pulpal and periapical pain.
AB  - A retrospective survey was designed to identify diagnostic subgroups and clinical
      factors associated with odontogenic pain and discomfort in dental urgency
      patients. A consecutive sample of 1,765 patients seeking treatment for dental
      pain at the Urgency Service of the Dental School of the Federal University of
      Goias, Brazil, was selected. Inclusion criteria were pulpal or periapical pain
      that occurred before dental treatment (minimum 6 months after the last dental
      appointment), and the exclusion criteria were teeth with odontogenic
      developmental anomalies and missing information or incomplete records. Clinical
      and radiographic examinations were performed to assess clinical presentation of
      pain complaints including origin, duration, frequency and location of pain,
      palpation, percussion and vitality tests, radiographic features, endodontic
      diagnosis and characteristics of teeth. Chi-square test and multiple logistic
      regression were used to analyze association between pulpal and periapical pain
      and independent variables. The most frequent endodontic diagnosis of pulpal pain
      were symptomatic pulpitis (28.3%) and hyperreactive pulpalgia (14.4%), and the
      most frequent periapical pain was symptomatic apical periodontitis of infectious
      origin (26.4%). Regression analysis revealed that closed pulp chamber and caries
      were highly associated with pulpal pain and, conversely, open pulp chamber was
      associated with periapical pain (p<0.001). Endodontic diagnosis and local factors
      associated with pulpal and periapical pain suggest that the important clinical
      factor of pulpal pain was closed pulp chamber and caries, and of periapical pain
      was open pulp chamber.

PMID- 21861031
TI  - Frequency of oral mucositis and microbiological analysis in children with acute
      lymphoblastic leukemia treated with 0.12% chlorhexidine gluconate.
AB  - In view of the morbidity potential of oral complications in patients with
      leukemia, this study evaluated the clinical and microbiological alterations that
      occur in the oral mucosa of children with acute lymphoblastic leukemia (ALL)
      undergoing antineoplastic chemotherapy and prophylactic administration of 0.12%
      chlorhexidine gluconate. The sample consisted of 17 children aged 2 to 12 years
      that underwent clinical examination of the oral mucosa for the detection of oral
      lesions. In addition, biological material was collected from labial and buccal
      mucosa for microbiological analysis. Oral mucositis was observed in only 5
      (29.4%) patients. Microbiological analysis revealed a reduced number of
      potentially pathogenic microorganisms, such as coagulase-negative staphylococci
      (47%), Candida albicans (35.3%), Klebsiella pneumoniae (5.9%), enteropathogenic
      Escherichia coli (5.9%), and Stenotrophomonas maltophilia (5.9%). Patients with
      oral mucositis showed a higher frequency of coagulase-negative staphylococci
      (80%) when compared with patients with normal oral mucosa (33.3%). In conclusion,
      the results of the present study suggest that the prophylactic use of 0.12%
      chlorhexidine gluconate reduces the frequency of oral mucositis and oral
      pathogens in children with ALL. In addition, the present findings suggest a
      possible relationship between coagulase-negative staphylococci and the
      development of oral mucositis.

PMID- 21861032
TI  - Effect of bleaching protocols with 38% hydrogen peroxide and post-bleaching times
      on dentin bond strength.
AB  - This study assessed the effect of bleaching protocols with 38% hydrogen peroxide
      (HP) and post-bleaching times on shear bond strength of a composite resin to
      dentin. One-hundred slabs of intracoronary dentin were included and randomly
      assigned into 2 groups according to the bleaching protocol: HP (2 applications of
      10 min each) and HP activated by LED laser (2 applications of 10 min each/45 s of
      light activation). Groups were subdivided according to the post-bleaching time
      (n=10): 1 day, 3 days, 7 days, 10 days and 14 days. The control group was
      unbleached and restored (n=10). The specimens were restored with Single Bond
      adhesive system/Filtek Z250 resin using a polytetrafluorethylene matrix and were
      submitted to the shear bond strength testa after 24 h,. Data were analyzed by
      ANOVA and Tukey's test (alpha=0.05). Unbleached group (0.283 +/- 0.134) had the
      highest bond strength and was statistically similar (p>0.05) to HP/10 days (0.278
      +/- 0.064), HP + LED laser/10 days (0.280 +/- 0.078), HP/14 days (0.281 +/-
      0.104), HP + LED laser/14 days (0.277 +/- 0.093). Lower bond strength were
      verified in HP/1 day (0.082 +/- 0.012), HP/3 days (0.079 +/- 0.013), HP + LED
      laser/1 day (0.073 +/- 0.018) and HP + LED laser/3 days (0.080 +/- 0.015), which
      were statistically similar (p>0.05). HP/7 days (0.184 +/- 0.154) and HP + LED
      laser/7 days (0.169 +/- 0.102) had intermediate values (p<0.05). The restorative
      procedure of intracoronary dentin bleached with 38% HP with or without the use of
      light source should be performed after at least 10 days after the bleaching
      treatment.

PMID- 21861033
TI  - Repair of critical-size defects with autogenous periosteum-derived cells combined
      with bovine anorganic apatite/collagen: an experimental study in rat calvaria.
AB  - The aim of this study was to evaluate the bone repair using autogenous periosteum
      derived cells (PDC) and bovine anorganic apatite and collagen (HA-COL). PDC from
      Wistar rats (n=10) were seeded on HA-COL discs and subjected to osteoinduction
      during 6 days. Critical-size defects in rat calvarias were treated with blood
      clot (G1), autogenous bone (G2), HA-COL (G3) and HA-COL combined with PDC (G4)
      (n=40), and then analyzed 1 and 3 months after surgeries. Radiographic analysis
      exhibited no significant temporal change. G1 and G2 had discrete new marginal
      bone, but the radiopacity of graft materials in G2, G3 and G4 impaired the
      detection of osteogenesis. At 3 months, histopathological analysis showed the
      presence of ossification islets in G1, which was more evident in G2, homogeneous
      new bone around HA-COL in G3 and heterogeneous new bone around HA-COL in G4 in
      addition to moderate presence of foreign body cells in G3 and G4.
      Histomorphometric analysis showed no change in the volume density of xenograft
      (p>0.05) and bone volume density in G2 was twice greater than in G1 and G4 after
      3 months (p<0.05), but similar to G3. The PDC did not increase bone formation in
      vivo, although the biomaterial alone showed biocompatibility and osteoconduction
      capacity.

PMID- 21861034
TI  - The nance lingual arch: an auxiliary device in solving lower anterior crowding.
AB  - After exfoliation of the primary incisors and eruption of the permanent incisors,
      the dentist has the opportunity of observing closely the beginning of occlusal
      changes. In several cases, alterations, such as lower anterior crowding, can be
      prevented and treated with proper follow-up. In the mixed dentition, one of the
      mechanisms for maintaining space and favoring dental alignment is to preserve
      leeway space before permanent second molar irruption. Among the devices with this
      function, the Nance lingual arch helps maintaining the position of the permanent
      mandibular molars and incisors after a premature loss of the primary canines.
      This paper describes the applicability of Nance lingual arch for preserving
      leeway space, thus contributing for correction of lower anterior crowding.

PMID- 21861035
TI  - Skeletal alterations associated with the use of bonded rapid maxillary expansion
      appliance.
AB  - Bonded maxillary expansion appliances have been suggested to control increases in
      the vertical dimension of the face after rapid maxillary expansion (RME).
      However, there is still no consensus in the literature about its real skeletal
      effects. The purpose of this prospective study was to evaluate, longitudinally,
      the vertical and sagittal cephalometric alterations after RME performed with
      bonded maxillary expansion appliance. The sample consisted of 26 children, with a
      mean age of 8.7 years (range: 6.9-10.9 years), with posterior skeletal crossbite
      and indication for RME. After maxillary expansion, the bonded appliance was used
      as a fixed retention for 3.4 months, being replaced by a removable retention
      subsequently. The cephalometric study was performed onto lateral radiographs,
      taken before treatment was started, and again 6.3 months after removing the
      bonded appliance. Intra-group comparison was made using paired t test. The
      results showed that there were no significant sagittal skeletal changes at the
      end of treatment. There was a small vertical skeletal increase in five of the
      eleven evaluated cephalometric measures. The maxilla displaced downward, but it
      did not modify the facial growth patterns or the direction of the mandible
      growth. Under the specific conditions of this research, it may be concluded that
      RME with acrylic bonded maxillary expansion appliance did promote signifciant
      vertical or sagittal cephalometric alterations. The vertical changes found with
      the use of the bonded appliance were small and probably transitory, similar to
      those occurred with the use of banded expansion appliances.

PMID- 21861036
TI  - Occurrence of skeletal malocclusions in Brazilian patients with dentofacial
      deformities.
AB  - In this study, a survey was conducted on the occurrence of skeletal malocclusions
      presented by patients of the Center for Research and Treatment of Buccofacial
      Deformities (CEDEFACE) in the city of Araraquara, SP, Brazil. The clinical charts
      of 381 patients with dentoskeletal deformities, who underwent combined
      orthodontic-surgical treatment in the period between 2000 and 2006, were
      reviewed. After sample selection (convenience method), based on the data of the
      pre- and post-surgical documentation, the number of patients was reduced to 171.
      For classification of the survey, the anteroposterior discrepancy (Class I, II
      and III), race, age, gender, absence or presence of asymmetry, vertical maxillary
      excess and maxillary biprotrusion were considered, in addition to determining in
      which bony base the surgical procedure was performed. Patients' documentations
      were analyzed by one examiner previously calibrated by repetition of the process
      until the method was considered adequate (intraclass correlation coefficient >
      0.94). Patients' mean age was 23.59 (SD 6.93) years, the majority (102 patients)
      were women, and Caucasians (160 patients). Class III malocclusion was the most
      prevalent (81 patients). Asymmetry, vertical maxillary excess and biprotrusion
      were present in 54, 33, and 7 patients, respectively. The majority of surgeries
      for correction of dentoskeletal deformities were combined, involving the maxilla
      and mandible. In conclusion, Class III was the most prevalent skeletal deformity
      and Class I was the least prevalent; in general, the prevalence of skeletal
      deformities was higher in women; in the majority of patients with skeletal
      malocclusions there was a combination of maxillary and mandibular problems, which
      interferes directly in the decision regarding the most adequate treatment plan,
      and a higher incidence of asymmetry was observed in skeletal Class III; vertical
      excess occurred in a similar manner in Class II and III and there was a low
      incidence of biprotrusion among the malocclusions evaluated.

PMID- 21861037
TI  - Permanent mandibular incisor with multiple anomalies - report of a rare clinical
      case.
AB  - Permanent mandibular central incisor is rarely affected by tooth shape anomalies
      of crown and root. Co-occurrence of multiple anomalies in a permanent mandibular
      central incisor is extremely rare. This paper reports an unusual concurrent
      combination of multiple dental anomalies affecting both the crown and root of a
      permanent mandibular left central incisor - talon cusp, dens invaginatus, short
      root anomaly and macrodontia -, which has not previously been reported together.
      Case management is described and implications are discussed. The dentist should
      be aware of these rare entities in order to provide an accurate diagnosis and
      management for which detailed examination of the tooth both clinically and
      radiographically is very important.

PMID- 21861038
TI  - Safety of ablation for atrial fibrillation with therapeutic INR: comparison with
      transition to low-molecular-weight heparin.
AB  - BACKGROUND: The ideal management of oral anticoagulation (OAC) before and after
      catheter ablation for atrial fibrillation (AF) is still controversial. OBJECTIVE:
      To compare two anticoagulation strategies for catheter ablation for AF: warfarin
      withholding and use of low-molecular-weight heparin (LMWH); and maintenance of
      warfarin and therapeutic INR (between 2.0 and 3.0). METHODS: 140 patients (pt)
      with persistent/permanent AF undergoing catheter ablation for AF were divided
      into two groups: Group I (70 pt), in which warfarin was withheld five days prior
      to the procedure and transition to LMWH was used (enoxaparin: 1 mg/kg 2x/day
      before ablation, and 0.5 mg/kg 2x/day after ablation); Group II (70 pt), in which
      warfarin was not withheld and the procedure was performed with therapeutic INR.
      Both groups received intravenous heparin (ACT > 350 seconds) during ablation.
      RESULTS: In Group I, one pt (1.4%) had a major hemorrhagic complication and four
      pts (5.7%) had minor hemorrhagic complications. In Group II, two pts (2.8%) had
      minor hemorrhagic complications and one pt had a major bleeding, which occurred
      after using LMWH due to INR < 2.0. None of the groups had thromboembolic
      complications or cardiovascular death over a period of 16 +/- 8 months.
      CONCLUSION: Catheter ablation for AF without withholding OAC and with therapeutic
      INR is a strategy that has similar safety and efficacy when compared with the
      traditional transition to LMWH, avoiding the potentially inadequate
      anticoagulation of the initial post-ablation period.

PMID- 21861039
TI  - Vegetation replacement in Rio de Janeiro during the last 7,000 years B.C.,
      genetic variation in the medicinal plant Lippia alba (Verbenaceae), and short
      review of Chagas disease in prehistory.

PMID- 21861043
TI  - Evaluation of the altimetry from SRTM-3 and planimetry from high-resolution
      PALSAR FBD data for semi-detailed topographic mapping in the Amazon Region.
AB  - The Brazilian Amazon has a deficit of 35% of coverage regarding topographic
      mapping at semi-detailed (1:100,000) scale. This paper presents an alternative to
      overcome this scenario using a combination of planialtimetric information from
      two orbital SAR (Synthetic Aperture Radar) missions. The altimetry was acquired
      from Shuttle Radar Topography Mission (SRTM), while the planimetry was provided
      from Fine Beam Dual (FBD) images of the Phased Array L-band Synthetic Aperture
      Radar (PALSAR) sensor. The research was carried out in the mountainous area of
      the Serra dos Carajas (Para State), located on the Amazon region. The quality of
      the orbital topographic information was evaluated regarding precise
      planialtimetric measurements acquired from Global Positioning System (GPS) field
      campaigns. The evaluations were performed following two approaches: (1) the use
      of Root Mean Square Error (RMSE) and (2) tendency and precision hypothesis tests.
      The investigation has shown that the planialtimetric quality of the orbital
      products fulfilled the Brazilian Map Accuracy Standards requirements for
      1:100,000 A Class map. Thus, the use of combination of information provided by
      PALSAR and SRTM-3 data can be considered a promising alternative for production
      and update of semi-detailed topographic mapping in similar environments of the
      Amazon region, where topographic information is lacking or presents low quality.

PMID- 21861044
TI  - Physicochemical characteristics and pollen spectra of organic and non-organic
      honey samples of Apis mellifera L.
AB  - The aim of this research was to analyze and compare 17 honey samples, 11 organic
      and six non-organic Apis mellifera honey. The samples were analyzed concerning
      moisture, hydroxymethylfurfural, diastase index, water activity, color, total
      sugar, reducing sugar, sucrose, ash, viscosity, electrical conductivity, pH,
      acidity, and formol index. With the exception of acidity, reducing sugar and
      diastase index, the averages of other parameters were different between the two
      groups. All samples of organic honey presented moisture values between 23.50 and
      24.40%. Among the nonorganic honey samples, two presented apparent sucrose amount
      upper the maximum limit established by the Brazilian Legislation. According to
      the quantitative analysis of pollen sediments in the honey samples and frequency
      of pollen types in 17 honey samples, 41.20% were classified as unifioral, and the
      remainder as polifioral.

PMID- 21861045
TI  - Agronomic efficiency of intercropping tomato and lettuce.
AB  - Four experiments were carried out at the Sao Paulo State University, Brazil, with
      the aim of determining the agronomic viability of intercropping tomato and
      lettuce, under greenhouse conditions. The studied intercropping systems were
      established by transplanting lettuce at 0, 10, 20 and 30 days after transplanting
      (DAT) tomato and by transplanting tomato at 0, 10, 20 and 30 DAT lettuce.
      Intercropped tomato and lettuce were evaluated during two seasons and compared to
      their sole cropping. The experimental design was a randomized complete block with
      nine treatments. The productivity and the classification of the tomato fruits
      were not influenced by having lettuce intercropped with it, but lettuce
      production was lowered when tomato was intercropped with it. The longer the delay
      in lettuce transplanting, the greater the reduction in its productivity. There
      was an effect of cropping season on the extent of the agronomic advantage of
      intercropping over sole cropping. In the first cropping season, intercropping
      established by transplanting lettuce during the interval between 30 days before
      up to 20 DAT tomato yielded land use efficiency (LUE) indices of 1.63 to 2.22. In
      the second period, intercropping established with the transplanting of lettuce up
      to 30 days before tomato yielded LUE indices of 1.57 to 2.05.

PMID- 21861046
TI  - [Long term depression of the recurrent inhibition of monosynaptic spinal reflexes
      after sciatic nerve crush in adult rats].
AB  - Sciatic nerve injury is a common disease of peripheral nerve in clinic. After
      nerve injury, there are many dysfunctions in motoneurons and muscles following
      regeneration. Previous studies mostly investigated the aspects related to the
      injured nerve, and the effect on the recurrent inhibition (RI) pathway of spine
      following regeneration was not fully understood. Following reinnervation after
      temporary sciatic nerve crush, the functional alteration of RI was studied. In
      adult rats, RI between lateral gastrocnemius-soleus (LG-S) and medial
      gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes
      (MSRs) elicited from the cut dorsal roots and recorded from either the LG-S or MG
      nerves by antidromic stimulation of the synergist muscle nerve. The following
      results were obtained. (1) The RI of MSRs in rats was almost lost (<5 weeks)
      after sciatic nerve crush. Although the RI partially recovered following
      reinnervation (6 weeks), it remained permanently depressed (up to 14 weeks). (2)
      Sciatic nerve crush on one side did not affect the contralateral RI. (3) Sciatic
      nerve crush did not induce any motoneuron loss revealed by immunohistochemistry.
      Peripheral nerve temporary disconnection causes long term alterations in RI
      pathway which make up motoneuron's function enhance for the alteration of muscle
      power and suggests that peripheral nerve injury induces long term plastic changes
      in the spinal motoneuron circuitry.

PMID- 21861047
TI  - [Effects of neonatal isolation stress on hyperlocomotion of complexin II knockout
      mouse].
AB  - The aim of this study was to investigate the influence of neonatal isolation
      stress on hyperlocomotion in complexin II knockout mouse (Cplx2(-/-)). The mice
      were randomly divided into 4 groups: Cplx2(-/-) with stress, Cplx2(+/+) with
      stress, Cplx2(-/-) without stress and Cplx2(+/+) without stress. Isolation stress
      was employed on the pups of stress groups from the 2nd day after the postnatal to
      the 21st day. The PCR was used to determine the gene type and the hyperlocomotion
      test was employed to detect the change of animal behavior after methamphetamine
      or saline injection (i.p.). The results showed that the animals of all groups
      increased their movement after injection of 0.2 mg/kg methamphetamine in
      different levels (P < 0.01), compared with those injected with saline. The Cplx2(
      /-) mouse with stress revealed a significant increase in the distance of free
      movement after injection of 0.2 mg/kg methamphetamine compared with the knockout
      mouse without stress (P < 0.001). When Cplx2(-/-) mouse with stress was compared
      with wild type with stress, Cplx2(-/-) mouse with stress had more movement (P <
      0.001), indicating that Cplx2 has effect on the hyperlocomotion as well. These
      results suggest an involvement of stress and Cplx2 in the movement behavior of
      mice.

PMID- 21861048
TI  - [High-frequency electro-acupuncture stimulation modulates intracerebral gamma
      aminobutyric acid content in rat model of Parkinson's disease].
AB  - The purpose of the present study is to observe the effect of electro-acupuncture
      (EA) stimulation on intracerebral neurotransmitters in a rat model of Parkinson's
      disease (PD), and explore the possible mechanism. We used 6-hydroxydopamine (6
      OHDA) injection in medial forebrain bundle (MFB) in the right brain of Sprague
      Dawley (SD) rat to establish the parkinsonian rat model, and randomly divided the
      PD rats into model and 100 Hz EA stimulation groups (n =10 in each group). EA
      stimulation group received 4 courses of EA stimulation on Baihui (GV-20) and
      Dazhui (GV-14) acupuncture points. Moreover, ten rats were randomly selected as
      sham operation group, only receiving normal saline (NS) injection in MFB. Then
      apomorphine (APO)-induced rotational behavior in different groups was recorded,
      and the contents of gamma-aminobutyric acid (GABA) in the brain were analyzed
      with high pressure/performance liquid chromatography-electrochemical detection
      (HPLC-ECD). The results showed that model group exhibited abnormal rotational
      behavior with APO treatment, suggesting the successful establishment of PD model.
      Compared with sham operation group, model group showed increased GABA contents in
      cortex and striatum, as well as decreased GABA content in ventral midbrain, on
      the lesioned side. EA stimulation could effectively ameliorate the abnormal
      rotational behavior of PD rat. Compared with the model group, EA stimulation
      decreased the ratio of GABA content on the lesioned side to that on unlesioned
      side in the cortex, while increased the ratios in the striatum and cerebellum.
      However, there was no difference of the ratio in the ventral midbrain among three
      groups. These results suggest high-frequency EA stimulation significantly
      improves the abnormal behavior of PD rats, which may exert through enhancing the
      inhibitory effect of cerebellum-basal ganglia-cortical loop on motor center.

PMID- 21861049
TI  - [Effects and mechanism of low frequency stimulation of pedunculopontine nucleus
      on spontaneous discharges of ventrolateral thalamic nucleus in rats].
AB  - Parkinson's disease is a progressive neurodegenerative disorder characterized
      clinically by rigidity, akinesia, resting tremor and postural instability. It has
      recently been suggested that low frequency stimulation of the pedunculopontine
      nucleus (PPN) has a role in the therapy for Parkinsonism, particularly in gait
      disorder and postural instability. However, there is limited information about
      the mechanism of low frequency stimulation of the PPN on Parkinson's disease. The
      present study was to investigate the effect and mechanism of low frequency
      stimulation of the PPN on the firing rate of the ventrolateral thalamic nucleus
      (VL) in a rat model with unilateral 6-hydroxydopamine lesioning of the substantia
      nigra pars compacta. In vivo extracellular recording and microiontophoresis were
      adopted. The results showed that the firing rate of 60.71% VL neurons in normal
      rats and 59.57% VL neurons in 6-hydroxydopamine lesioned rats increased with low
      frequency stimulation of the PPN. Using microiontophoresis to VL neurons, we
      found the firing rate in VL neurons responded with either an increase or decrease
      in application of acetylcholine (ACh) in normal rats, whereas with a predominant
      decrease in M receptor antagonist atropine. Furthermore, the VL neurons were
      mainly inhibited by application of gamma-aminobutyric acid (GABA) and excited by
      GABA(A) receptor antagonist bicuculline. Importantly, the VL neurons responding
      to ACh were also inhibited by application of GABA. We also found that the
      excitatory response of the VL neurons to the low frequency stimulation of the PPN
      was significantly reversed by microiontophoresis of atropine. These results
      demonstrate that cholinergic and GABAergic afferent nerve fibers may converge on
      the same VL neurons and they are involved in the effects of low frequency
      stimulation of the PPN, with ACh combining M(2) receptors on the presynaptic
      membrane of GABAergic afferents, which will inhibit the release of GABA in the VL
      and then improve the symptoms of Parkinson's disease.

PMID- 21861050
TI  - [A study on the neuronal mechanism of retrieval of long-term digital memory in
      human by functional magnetic resonance imaging].
AB  - To investigate the neuronal mechanism of retrieval of long-term digital memory in
      healthy volunteers, functional magnetic resonance imaging (fMRI) technique was
      used in the study. Twenty-two right-handed volunteers were subjected to a long
      term digital memory test with block-design. The memory task and control task were
      adopted in the experiment alternatively. The fMRI data were recorded by a Siemens
      1.5T MR machine and analyzed by SPM99. The activated brain regions were shown in
      the Talairach coordinate. The results showed that the Brodmann's area (BA) 9
      region in left middle frontal gyrus was the most activated cortex during the long
      term digital memory task. The left medial frontal gyrus, left inferior frontal
      gyrus, right inferior frontal gyrus, cingulate gyrus, left inferior parietal
      lobule, left superior parietal lobule, right superior parietal lobule, right
      middle temporal gyrus, left lingual gyrus, left middle occipital gyrus, right
      middle brain, cerebellum and right caudate nucleus tail were also involved. The
      activation in cortices showed obvious left predominance. It is suggested that a
      series of brain regions with left predominance are involved in long-term digital
      memory. Left lateral frontal cortex would be the most important structure for
      information extraction, while the other cortices and their connections may be
      important for processing and long-term storage of digital information.

PMID- 21861051
TI  - [Down-regulation of PTEN expression in kidney and its role in development of
      diabetic nephropathy in rats].
AB  - Transforming growth factor-beta1 (TGF-beta1)-activated phosphoinositide-3-kinase
      (PI3K)-protein kinase B (PKB/Akt) pathway is intimately related to the
      development of diabetic nephropathy (DN), which is negatively regulated by
      phosphatase and tensin homolog deleted on chromosome ten (PTEN). The present
      study was to investigate the expression of PTEN in the renal tissue of diabetic
      mellitus (DM) rats and explore its possible effect on development of DN. Sixteen
      Sprague-Dawley rats were divided into normal control group (n = 8) and diabetic
      group (n = 8) at random. Streptozotocin injection was used to establish diabetic
      model. After 12 weeks, the rats were sacrificed to detect relative biochemical
      parameters and renal index, and to observe the changes of pathomorphology by HE
      staining as well. In addition, immunohistochemistry staining and Western blotting
      were employed to detect the protein expression of PTEN, TGF-beta1, PI3Kp110alpha,
      Akt1, p-Akt1 (Ser(473)), fibronectin (FN) and Collagen IV, respectively.
      Furthermore, the expression of PTEN mRNA was also examined by RT-PCR. The results
      indicated that the levels of blood glucose, serum creatinine and urine protein
      (24 h) were increased remarkably in the diabetic group (P < 0.05) compared with
      those in the control group. Compared with those in the control group, the protein
      expressions of TGF-beta1, PI3Kp110alpha, Akt1 in renal tubular epithelium and the
      expressions of FN and CollagenIV in renal interstitium were increased in the
      diabetic group (P < 0.05). The expression of PTEN in the diabetic group was
      significantly reduced than that in the control group (P < 0.05), and the
      expression of p-Akt1 (Ser(473)) increased remarkably in the diabetic group which
      had the similar trend to Akt1 (P < 0.05). PTEN mainly located in renal tubular
      epithelial cells. The expression of PTEN had negative correlation to that of p
      Akt1 (Ser(473)). Compared with that in the control group, the expression of PTEN
      mRNA was decreased remarkably in the diabetic group (P < 0.05). The data suggest
      that the down-regulation of PTEN in renal tissue of DM rats may promote the PI3K
      PKB/Akt pathway over-activated by TGF-beta1, which facilitates the initiation and
      development of DN.

PMID- 21861052
TI  - [Activation of hippocampal D1 dopamine receptor inhibits glutamate-mediated
      depression induced by chronic unpredictable mild stress in rats].
AB  - The present study was to investigate the role of dopamine D1 receptors and its
      relationship with glutamate, N-methyl-D-aspartic acid (NMDA) receptor and alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor in depression
      induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression
      model was established in Sprague-Dawley rats, and intrahippocampal
      microinjections of D1 dopamine receptor agonist SKF38393, non-competitive NMDA
      receptor antagonist MK-801 and AMPA receptor antagonist NBQX were respectively
      adopted by rat brain stereotaxic coordinates. The behavioral observations were
      conducted by measurement of weight changes, sucrose preference test, open-field
      test and tail suspension test. The concentration of glutamic acid and the
      expression of its receptors' subunits were detected by HPLC and Western blot,
      respectively. The results showed that, compared with control group, CUMS rats
      showed depression-like behavioral changes, higher concentration of glutamic acid,
      lower expressions of NMDA receptor (NR1) and AMPA receptor (GluR2/3) in
      hippocampus. Pretreatment with injection of SKF38393 could rescue such depression
      effect of CUMS, decrease the concentration of glutamic acid, and increase the
      expressions of NMDA receptor (NR1), AMPA receptor (GluR2/3) in hippocampus.
      Pretreatment with MK-801 could enhance the antidepressant effect of SKF38393,
      while NBQX weakened. These results suggest that agonists of D1 dopamine receptor
      could reduce the concentration of glutamic acid in hippocampus, and its
      antidepressant effect may be mediated by AMPA receptor partially.

PMID- 21861053
TI  - [Comparisons of endocrine hormones levels between Tibetan antelope and Tibetan
      sheep].
AB  - The Tibetan antelope, a prototype mammal, has developed a unique adaptation to
      extreme high altitude-associated hypoxia. To investigate the role of the
      endocrine system in adaptation to high altitude in the Tibetan antelope,
      comparisons of endocrine hormones levels between Tibetan antelope (n = 9) and
      Tibetan sheep (n = 10) were performed. Both two kinds of animals were captured at
      an altitude of 4 300 m and then transported to experimental base at 2 800 m
      altitude. The blood samples were drawn from right external jugular vein in the
      next morning, and the 20 hormones in hypothalamus-adenohypophysis-peripheral
      hormonal axis were measured with radioimmunoassay or enzyme-linked immunosorbent
      assay. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and mean pulmonary arterial pressure (mPAP) were recorded using
      catheterization. Moreover, hemoglobin (Hb) content was measured by blood
      analyser. The results showed that, the levels of FT(3), FT(4) and Ang II in
      Tibetan antelope were significantly lower than those in Tibetan sheep, whereas
      TRH, CRH, GHRH, F, E(2), Ald, ACTH and CGRP levels were significantly greater in
      Tibetan antelope than those in the Tibetan sheep. Compared with Tibetan sheep,
      Tibetan antelope showed lower HR, mPAP, SBP, DBP and Hb content. In Tibetan
      antelope and Tibetan sheep, both Hb and Ang II were correlated positively with
      respective mPAP. In Tibetan antelope, FT(3) level was correlated positively with
      GH and negatively with ACTH. These results suggest that the endocrine system of
      Tibetan antelope is characterized by low energy expenditure and high stress,
      which may be one of the mechanisms underlying the Tibetan antelope adaptation to
      chronic hypoxia.

PMID- 21861054
TI  - [Effects of hypoxia on iron metabolism of rat L6 skeletal muscle cells].
AB  - The present study was aimed to investigate the effects of hypoxia on iron
      metabolism of skeletal muscle. Rat L6 skeletal muscle cells were randomly divided
      into three groups which were exposed to hypoxia (1% O(2)) for 0, 12, 24 h,
      respectively. Iron isotope tracing method was used to determine iron uptake and
      release. Iron content of labile iron pool (LIP) was investigated by flow
      cytometry, and the expressions of transferrin receptor 1 (TfR1), divalent metal
      transporter 1 (DMT1), ferroportin 1 (FPN1), hypoxia-inducible transcription
      factor-1 (HIF-1) in L6 cells were observed by Western blot. The results showed
      that, compared with 0-hour hypoxia group, 12-hour hypoxia group exhibited
      significantly increased iron uptake and LIP (P < 0.05), as well as decreased iron
      release (P < 0.01). Not only iron uptake and release, but also LIP in 24-hour
      hypoxia group were significantly decreased, compared with those in 0- and 12-hour
      hypoxia groups (P < 0.01). The expressions of HIF-1, DMT1 (IRE), DMT1 (non-IRE)
      and TfR1 in 12-hour hypoxia group were significantly increased compared with
      those in 0-hour hypoxia group (P < 0.01). On the contrary, the expressions of
      DMT1 (IRE), DMT1 (non-IRE) and FPN1 in 24-hour hypoxia group were significantly
      decreased compared with those in the other two groups. However, TfR1 expression
      in 24-hour hypoxia was higher than those in 0- and 12-hour hypoxia groups (P <
      0.05 or P < 0.01). These results suggest hypoxia plays an important role in iron
      metabolism of skeletal muscle cells. Moderate hypoxia can increase iron uptake
      and decrease iron release, resulting in higher LIP, but a prolonged hypoxia
      induces a disordered iron metabolism of skeletal cells.

PMID- 21861055
TI  - [Inhibitory effect of hydrogen sulfide on cardiac fibroblast proliferation].
AB  - The aim of the present study was to investigate the role of hydrogen sulfide
      (H(2)S) in the proliferation of neonatal rat cardiac fibroblasts (NRCFs).
      Proliferation of NRCFs was induced by the presence of fetal bovine serum (FBS) or
      angiotensin II (Ang II) at various concentrations. The concentration-dependent
      effect of NaHS (donor of H(2)S) on NRCFs proliferation was examined. NRCFs
      proliferation was assessed by 5'-bromo-2'-deoxyuridine (BrdU) incorporation
      method. Reactive oxygen species (ROS) level was measured using the dye probe, 2',
      7'-dichlorofluorescein diacetate (DCFH-DA). The results showed that FBS- or Ang
      II-induced NRCFs proliferations were inhibited with the treatment of relatively
      high concentrations of NaHS (5 * 10(-5) mol/L, 1 * 10(-4) mol/L), but FBS-induced
      proliferation was increased by low concentration of NaHS (1 * 10(-5) mol/L). Two
      or 6 h of Ang II (1 * 10(-7) mol/L) treatment caused an increase of ROS level in
      NRCFs, while this increase was inhibited with NaHS (1 * 10(-4) mol/L) treatment.
      These results suggest that H(2)S is an inhibitor of cardiac fibroblast at a
      certain concentration range. This inhibitory effect may be mediated by a
      reduction in intracellular ROS production.

PMID- 21861056
TI  - [Rat bone marrow mesenchymal stem cells-differentiated endothelial like cells
      facilitate angiogenesis and the Rho kinase contribution].
AB  - The aim of this study was to investigate the influence of endothelial like cells
      differentiated from rat bone marrow mesenchymal stem cells (rBMSC-ECs) on
      angiogenesis and the effect of Rho kinase (ROCK) inhibitor using an in vitro
      model of cells co-cultured with rat aorta ring. Cell proliferation capability was
      detected by MTT method. The rBMSC-ECs were co-cultured with rat aorta ring in rat
      tail collagen and endothelial medium. A ROCK specific inhibitor, HA-1077 at
      different concentrations (0, 10, 30 and 60 mmol/L, respectively) was added into
      the medium of ring-cell co-culture. The protein expression of ROCK I and ROCK II
      were detected by Western blot. On the third day of cultivation, the branch number
      of neogenetic microvessels increased by 34.5% in ring-cell co-culture group
      compared with that in simple aorta ring group (P < 0.01). Compared with that in
      ring-cell co-culture group, it was significantly decreased by 57.70%, 64.13% and
      48.23% respectively in three concentrations of HA-1077 groups (all P < 0.01).
      However, on the sixth day, rBMSC-ECs proliferated and migrated to the nearby
      aorta ring, and the growth of microvessels became slow. On the ninth day, some of
      neogenetic microvessels were retracted, some became thicken, coarsen and
      lengthen, and some of rBMSC-ECs were sprouting and forming capillary like
      picture. The protein expression of ROCK I/II was slightly higher in ring-cell co
      culture group than that in simple aorta ring group. But, in three concentrations
      of HA-1077 groups, it was slightly lower than that in ring-cell co-culture group.
      By using rhodamine-phalloidin staining and laser scanning confocal fluorescence
      microscope, it showed that there were a lot of the F-actin cytoskeletons in
      neogenesis microvessels of aorta ring, and there were a lot of thick and long
      stress fibers in the cells. F-actin-rich surface protrusions at the leading edge
      of the cell were also shown. Another ROCK inhibitor, Y-27632 (10 MUmol/L) induced
      the actin cytoskeleton reorganization: F-actins appeared to be peripheral fibers
      at outer area of cell; stress fiber and filopodia disappeared. These results
      suggest that rBMSC-ECs themselves can be differentiated into new microvessels and
      facilitate angiogenesis when they are co-cultured with rat aorta ring. The
      mechanisms involve ROCK activation and F-actin cytoskeleton recombination.

PMID- 21861057
TI  - [Nitric oxide modulates biphasic changes of isolated lymphatic contraction in
      hemorrhagic shock rats].
AB  - The aim of the present study was to investigate the changes of lymphatic
      contraction after hemorrhagic shock in vitro and the underlying role of nitric
      oxide (NO). Rat thoracic duct segments were isolated at 0, 0.5, 1, 2 and 3 h
      after hemorrhagic shock. Using Pressure Myograph System, we determined
      contraction frequency (CF), end systolic diameter (ESD), end diastolic diameter
      (EDD) and passive diameter (PD) of isolated rat lymphatics under different
      transmural pressures (1, 3, 5, 7 and 9 cmH(2)O), then calculated contraction
      amplitude (CA), tonic index (TI) and fractional pump flow (FPF) of lymphatics.
      The results showed that in several transmural pressures, lymphatic CF, TI and FPF
      were significantly higher in shock 0 h and shock 0.5 h groups than those in
      control group (sham operation group). With the development of shock, lymphatic
      CF, TI and FPF decreased significantly in shock 2 h and shock 3 h groups compared
      with those in control group. We further discovered the role of NO in the changes
      of lymphatic contraction after hemorrhagic shock. Under 3 cmH(2)O transmural
      pressure, the changes of lymphatic contraction in shock 0.5 h and shock 2 h
      groups were analyzed following the incubation with several NO-related drugs alone
      or in combination. And the results showed that NO donor L-Arg reduced CF, TI and
      FPF in shock 0.5 h group to the control levels, while soluble guanylate cyclase
      inhibitor ODQ suppressed the effect of L-Arg. Moreover, NOS inhibitor L-NAME
      elevated the CF, TI and FPF of 2 h shock lymphatics to the control levels, while
      phosphodiesterase inhibitor aminophylline (AP) suppressed the effect of L-NAME.
      These results suggest that the lymphatic contractile activity exhibits a biphasic
      change during hemorrhagic shock, increasing in early phase and declining in later
      stage. And NO plays a major regulating role in the biphasic change of lymphatic
      contraction in hemorrhagic shock rats via cGMP pathway.

PMID- 21861058
TI  - [Prediction of ventilatory function in children and adolescents using
      backpropagation neural networks].
AB  - The aim of this study is to develop backpropagation neural networks (BPNN) for
      better prediction of ventilatory function in children and adolescents. Nine
      hundred and ninety-nine healthy children and adolescents (500 males and 499
      females) aged 10-18 years, all of the Han Nationality, were selected from Inner
      Mongolia Autonomous Region, and their heights, weights, and ventilatory functions
      were measured respectively by means of physical examination and spirometric test.
      Using the approaches of BPNN and stepwise multiple regression, the prediction
      models and equations for forced vital capacity (FVC), forced expiratory volume in
      one second (FEV1), peak expiratory flow (PEF), forced expiratory flow at 25% of
      forced vital capacity (FEF25%), forced expiratory flow at 50% of forced vital
      capacity (FEF50%), maximal mid-expiratory flow (MMEF) and forced expiratory flow
      at 75% of forced vital capacity (FEF75%) were established. Through analyzing mean
      squared difference (MSD) and correlation coefficient (R) of the ventilatory
      function indexes, the present study compared the results of BPNN, linear
      regression equation based on this work (LR's equation), prediction equations
      based on the studies of Ip et al. (Ip's equation) and Zapletal et al. (Zapletal's
      equation). The results showed, regardless of sex, the BPNN prediction models
      appeared to have smaller MSD and higher R values, compared with those from the
      other prediction equations; and the LR's equation also had smaller MSD and higher
      R values compared with those from Ip's and Zapletal's equations. The coefficients
      of variance (CV) for FEF50%, MMEF and FEF75% were higher than those of the other
      ventilatory function parameters, and their increasing percentages of R values
      (DeltaR, relative to R values by LR's equation) derived by BPNN were
      correspondingly higher than those of the other indexes. In sum, BPNN approach for
      ventilatory function prediction outperforms the traditional regression methods.
      When CV of a certain ventilatory function parameter is higher, the superiority of
      BPNN would be more significant compared with traditional regression methods.

PMID- 21861059
TI  - [Glucagon like peptide-1 inhibits high glucose-induced injury of oxidative stress
      in cardiomyocytes of neonatal rats].
AB  - The present study was to investigate the effect of glucagon like peptide-1 (GLP
      1) on high glucose-induced oxidative stress of cardiomyocytes and the possible
      role of the PI3K-Akt signal path in this process in the neonatal SD rats. With
      enzymatic digestion and immunofluorescence identification, cardiomyocytes after
      72-96 h of primary culture were used in experiment. The cells were divided into 5
      groups: normal control group, high glucose group, high glucose + GLP-1 group,
      high glucose + GLP-1 + LY294002 group and high osmolarity control group. The
      content of MDA was detected by TBA colouration method. The content of SOD was
      detected by xanthine oxidase method. The change of NADPH P47phox subunit mRNA
      quantity was detected by PCR gel electrophoresis. The level of ROS was detected
      by flow cytometry, and was also observed by fluorescence microscope. The DNA
      ladder was examined by agarose gel electrophoresis, and the cell apoptosis was
      determined by Annexin-V-FITC/PI flow cytometry, and the phosphorylation of Akt
      was determined by Western blotting. Compared with those in the normal control
      group, in the high glucose group, the cells grew poorly, and the beating rate was
      significantly lower (P < 0.05); The apoptotic rate was significantly increased (P
      < 0.05); The MDA content was increased (P < 0.05); It showed the typical DNA
      ladder, which is the characteristic of apoptosis; The SOD activity was decreased
      (P < 0.05); The level of intracellular ROS increased (P < 0.05); And the
      expression of NADPH P47phox subunit mRNA was increased; However the
      phosphorylation level of Akt was decreased. Pretreatment with GLP-1 improved the
      above-mentioned parameters and decreased the expression of NADPH P47phox subunit
      mRNA (P < 0.05). However, compared with the high glucose + GLP-1 group, LY294002,
      an inhibitor of PI3K-Akt signal path, attenuated the protective effect of GLP-1
      in the high glucose + GLP-1 + LY294002 group. It is suggested that GLP-1 plays a
      protective role in the high glucose-induced injury and apoptosis of
      cardiomyocytes, and the PI3K-Akt signal path is involved in this process.

PMID- 21861060
TI  - [Neuroprotective role of silent information regulator 1 in Alzheimer's disease].
AB  - Silent information regulator 1 (SIRT1), an NAD(+)-dependent deacetylase, is
      involved in the regulation of gene transcription, energy metabolism and cell
      aging. Recent studies have showed that SIRT1 possesses neuroprotective effects,
      however, it is not very clear how SIRT1 exerts the neuroprotection in Alzheimer's
      disease (AD). In this review, we summarized the neuroprotective role of SIRT1 in
      AD and its possible molecular mechanisms, proposing a novel strategy for
      preventing and treating neurodegeneration.

PMID- 21861062
TI  - Effect of temperature on activity of third-stage larvae of Angiostrongylus
      vasorum.
AB  - To evaluate the effect of temperature on the activity and mortality of the L3 of
      Angiostrongylus vasorum, 1,500 L3 were isolated from experimentally infected
      snails and distributed into five equal groups. Three groups were incubated at 37
      degrees C, 27 degrees C, and 5 degrees C. The remaining two groups were incubated
      at 27 degrees C and 5 degrees C for 10 days, at which time the temperature for
      the 27 degrees C group was reduced to 5 degrees C and the 5 degrees C group
      increased to 27 degrees C. Larva activity was observed daily and inactive larvae
      were removed. At 37 degrees C, larvae survived up to 8 days. At 27 degrees C,
      larvae were active until day 6. When subjected to a reduction in temperature from
      27 degrees C to 5 degrees C beginning on day 10, the number of active larvae
      increased until day 13. Only on day 17 did the number of active larvae decline to
      zero. At 5 degrees C, larvae remained active until day 15, surviving to 24 days.
      When temperature was increased from 5 degrees C to 27 degrees C beginning on day
      10, larvae were found active until day 12 and maintained an intermediate level of
      activity to day 21. Survival of larvae was greater at lower temperatures, while
      high temperatures were associated with higher mortality.

PMID- 21861063
TI  - The viral RNA-based transfection of enhanced green fluorescent protein (EGFP) in
      the parasitic protozoan Trichomonas vaginalis.
AB  - Here we have developed methods to transiently and stably transfect the human
      pathogenic protist Trichomonas vaginalis. The viral RNA-based transfection vector
      pTVV-EGFP/NEO was constructed by using enhanced green fluorescent protein gene
      (EGFP) and neomycin resistance gene (NEO) in tandem to replace the whole gene
      encoding region of T. vaginalis virus (TVV). The in vitro transcripts of
      linearized pTVV-EGFP/NEO were electroporated into trophozoites and the
      transfectants transiently expressed EGFP after 16 h postincubation. Stable
      expression of EGFP was persistently detected by fluorescence microscopy and by RT
      PCR in transfected trophozoites under G418 selection. Our study provides a novel
      and valuable approach for genetic study of T. vaginalis.

PMID- 21861061
TI  - From sleep spindles of natural sleep to spike and wave discharges of typical
      absence seizures: is the hypothesis still valid?
AB  - The temporal coincidence of sleep spindles and spike-and-wave discharges (SWDs)
      in patients with idiopathic generalized epilepsies, together with the
      transformation of spindles into SWDs following intramuscular injection of the
      weak GABAA receptor (GABAAR) antagonist, penicillin, in an experimental model,
      brought about the view that SWDs may represent 'perverted' sleep spindles. Over
      the last 20 years, this hypothesis has received considerable support, in
      particular by in vitro studies of thalamic oscillations following
      pharmacological/genetic manipulations of GABAARs. However, from a critical
      appraisal of the evidence in absence epilepsy patients and well-established
      models of absence epilepsy it emerges that SWDs can occur as frequently during
      wakefulness as during sleep, with their preferential occurrence in either one of
      these behavioural states often being patient dependent. Moreover, whereas the EEG
      expression of both SWDs and sleep spindles requires the integrity of the entire
      cortico-thalamo-cortical network, SWDs initiates in cortex while sleep spindles
      in thalamus. Furthermore, the hypothesis of a reduction in GABAAR function across
      the entire cortico-thalamo-cortical network as the basis for the transformation
      of sleep spindles into SWDs is no longer tenable. In fact, while a decreased
      GABAAR function may be present in some cortical layers and in the reticular
      thalamic nucleus, both phasic and tonic GABAAR inhibitions of thalamo-cortical
      neurons are either unchanged or increased in this epileptic phenotype. In
      summary, these differences between SWDs and sleep spindles question the view that
      the EEG hallmark of absence seizures results from a transformation of this EEG
      oscillation of natural sleep.

PMID- 21861064
TI  - Efficacy of adulticidal and larvicidal properties of botanical extracts against
      Haemaphysalis bispinosa, Hippobosca maculata, and Anopheles subpictus.
AB  - The aim of the present study was to investigate the adulticidal and larvicidal
      activity of dried leaf hexane, ethyl acetate, acetone, and methanol extracts of
      Nelumbo nucifera, Manilkara zapota, Ipomoea staphylina, and Acalypha indica
      against the adults of Haemaphysalis bispinosa (Acarina: Ixodidae), hematophagous
      fly Hippobosca maculata (Diptera: Hippoboscidae), and fourth instar larvae of
      malaria vector Anopheles subpictus (Diptera: Culicidae). Parasites were exposed
      to varying concentrations of plant extracts for 24 h. All extracts showed
      moderate parasitic effects; however, the percent parasitic mortality observed in
      the crude leaf hexane, ethyl acetate, acetone, and methanol extracts of N.
      nucifera and M. zapota against H. bispinosa were 80, 74, 72, and 100 and 100, 83,
      74, and 91, respectively, and the activity for I. staphylina and A. indica
      against Hip. maculata were 100, 93, 87, and 66 and 78, 90, 87, and 100 at 2,000
      ppm, respectively; the larvicidal activity for the same extracts of I. staphylina
      against A. subpictus were 76, 82, 84, and 100 at 100 ppm, respectively. The
      maximum efficacy was observed in the leaf methanol extract of N. nucifera, hexane
      extract of M. zapota and leaf hexane extract of I. staphylina, and methanol
      extract of A. indica against the adults of H. bispinosa and Hip. maculata with
      LC(50) and LC(90) values of 437.14 and 200.81, and 415.14 and 280.72 ppm,
      1,927.57 and 703.52 ppm, and 1,647.70 and 829.39 ppm, respectively. The effective
      larvicidal activity was observed in leaf methanol extract of I. staphylina
      against A. subpictus with LC(50) and LC(90) values of 10.39 and 37.71 ppm,
      respectively. Therefore, this study provides the first report on the adulticidal
      and larvicidal activity of crude solvent extracts. This is an ideal eco-friendly
      approach for the control of H. bispinosa, Hip. maculata, and the medically
      important vector A. subpictus.

PMID- 21861066
TI  - Coping in caregivers of youth with spinal cord injury.
AB  - This study examined coping among caregivers of youth with spinal cord injuries
      (SCI). Using a cross-sectional survey study design, 164 caregivers completed a
      demographics questionnaire and the Brief COPE. Their children, youth with SCI
      ages 7-18, completed the Kidcope. T-tests were conducted to examine differences
      in caregiver coping by demographic and injury-related factors. Further, logistic
      regression models were evaluated to examine predictive relationships between
      caregiver coping and youth coping. Several demographic and injury-related factors
      were related to caregiver coping, including caregiver gender, race, and
      education, as well as youth gender, age at injury, and time since injury. In the
      logistic regressions, two caregiver coping strategies were related to youth
      coping: caregiver self-blame coping was related to youth self-criticism, and
      caregiver behavioral disengagement coping (giving up attempts to cope) was
      related to youth blaming others coping. The findings suggest that caregiver
      coping may play a role in the coping of their children, and should be considered
      when addressing coping among youth with SCI.

PMID- 21861067
TI  - Herpes simplex virus genital infections: current concepts.
AB  - Genital herpes is a common sexually transmitted disease that is frequently
      undiagnosed. Viral shedding occurs frequently and often without symptoms
      facilitating transmission to sex partners. Genital herpes may impact HIV
      transmission, and may be transmitted to neonates at the time of birth. Primary
      prevention of genital herpes is needed to lower the burden of disease.

PMID- 21861069
TI  - LOX-1 and angiotensin receptors, and their interplay.
AB  - The renin-angiotensin system (RAS) plays an important role in regulating blood
      pressure, water-salt balance and the pathogenesis of cardiovascular diseases.
      Angiotensin II (Ang II) is the physiologically active mediator and mediates the
      main pathophysiological actions in RAS. Ang II exerts the effects by activating
      its receptors, primarily type 1 (AT1R) and type 2 (AT2R). Most of the known
      pathophysiological effects of Ang II are mediated by AT1R activation. The precise
      physiological function of AT2R is still not clear. Generally, AT2R is considered
      to oppose the effects of AT1R. Lectin-like oxidized low-density lipoprotein
      scavenger receptor-1 (LOX-1) is one of the major receptors responsible for
      binding, internalizing and degrading ox-LDL. The activation of LOX-1 has been
      known to be related to many pathophysiological events, including endothelial
      dysfunction and injury, fibroblast growth, and vascular smooth muscle cell
      hypertrophy. Many of these alterations are present in atherosclerosis,
      hypertension, and myocardial ischemia and remodeling. A growing body of evidence
      suggests the existence of a cross-talk between LOX-1 and Ang II receptors. Their
      interplays are embodied in the reciprocal regulation of their expression and
      activity. Their interplays are involved in a series of signals. Recent studies
      suggests that reactive oxygen species (ROS), nitric oxide (NO), protein kinase C
      (PKC) and mitogen activated protein kinases (MAPKs) are important signals
      responsible for their cross-talk. This paper reviews these aspects of
      dyslipidemia and RAS activation.

PMID- 21861070
TI  - Impact of systemic venous congestion in heart failure.
AB  - Systemic venous congestion is one of the hallmarks of the syndrome of heart
      failure that results from activation of different deleterious neurohormonal
      pathways. Apart from contributing to patients' symptoms and hospital admissions,
      growing evidence suggests that congestion itself drives further heart failure
      progression. In addition, systemic venous congestion exerts detrimental effects
      on other organs (such as kidneys and liver) due to ineffective organ perfusion.
      Endothelial cell activation, altered ventricular geometry, and functional mitral
      insufficiency are among the proposed mechanisms. Diuretics and vasodilators
      remain the mainstay of treatment options, mostly because of poor understanding of
      the underlying cardiorenal mechanisms involved. Recently, ultrafiltration has
      emerged as an invasive treatment option in the setting of diuretic resistance.
      Congestion ideally should be prevented, often initially through water and salt
      restriction. Early detection, possibly with the help of novel implantable sensor
      technology, may allow for early detection and intervention long before overt
      congestion is established.

PMID- 21861071
TI  - Laparoscopic-assisted versus open resection of right-sided colonic cancer--a
      prospective randomized controlled trial.
AB  - PURPOSES: This study aims to compare the perioperative outcomes and survival
      between laparoscopic-assisted right hemicolectomy (LARH) and open right
      hemicolectomy (ORH) for right-sided colon cancer. METHODS: Between July 1996 and
      October 2005, 145 patients were randomized to receive LARH (n = 71) or ORH (n =
      74). RESULTS: The median follow-up of living patients was 99.7 months. The
      demographic data of the two groups were similar. The time to resume diet (4 vs. 5
      days, p = 0.045) and the hospital stay (7.8 vs. 10 days, p = 0.033) were
      significantly shorter in LARH group, but these benefits were at the expense of
      longer operating time (198 vs. 129 min, p = 0.002) and higher direct cost
      (USD8745 vs. USD6293, p < 0.001). The morbidity and mortality were comparable
      between the two groups. After curative resection, the probabilities of survival
      at 5 years of the LARH and ORH groups were 74.2% (SE 7.4%) and 75% (SE 7.1%),
      respectively. The probabilities of being disease free at 5 years were 82.3% (SE
      6.9%) and 84.1% (SE 6.2%), respectively. CONCLUSIONS: Laparoscopic-assisted
      resection of right-sided colonic cancer has the advantage over open surgery in
      allowing earlier recovery. However this is at the expense of a longer operating
      time and higher direct cost (registration number: NCT00485316 (
      http://www.clinicaltrials.gov )).

PMID- 21861072
TI  - Mentored trainees obtain comparable operative results to experts in complex
      laparoscopic colorectal surgery.
AB  - PURPOSE: The aim of this study is to evaluate the impact of an expert monitoring
      on the quality and results of laparoscopic reversal of Hartmann's procedure
      (LRHP) performed by trainee surgeons by comparing their results to the expert's
      outcomes. METHODS: Forty-two LRHP were performed between 2000 and 2008 following
      a step-by-step, standardised, full laparoscopic procedure. Patients operated upon
      by a senior surgeon were compared to patients operated upon by trainee surgeons
      while being mentored by the senior surgeon. Operative time, conversion,
      complications and post-operative outcome were measured. RESULTS: Each group
      included 21 patients. All patients underwent LRHP successfully. Two procedures
      were converted. No significant difference was observed between the expert and the
      trainees: operative time, 132 min (SD +/- 50) vs. 131 min (SD +/- 47) and
      complications (2-14%), 4 vs. 2. Three complications required re-operation, and
      three other were treated medically, including one dilatation of an anastomosis.
      Post-operative outcomes were comparable (oral intake, 3 vs. 2 days; post
      operative hospital stay, 6 vs. 7.5 days); no mortality occurred. CONCLUSIONS:
      Standardisation simplifies this difficult laparoscopic procedure and offers the
      same outcome whether it is performed by an expert or by mentored trainees. The
      complications were comparable to those occurring at experienced centres
      (anastomotic leak or stricture, ureteral injury, re-operation). The expert
      mentoring does not prevent all complications but can solve intra-operative
      technical problems, thus improving the trainee's confidence. Mentoring should be
      promoted as it can be performed locally or remotely using modern interactive
      technology.

PMID- 21861073
TI  - Violation of treatment guidelines -- hazard for rectal cancer patients.
AB  - AIM: The aim of this study was to evaluate temporal trends in treatment and
      outcome in rectal cancer diagnosed during 1980-2004 at Levanger Hospital.
      MATERIALS AND METHODS: A protocol for prospective registration of rectal cancer
      treated with total mesorectal excision including operative strategy, radiotherapy
      and surveillance was established at Levanger Hospital in 1980. In this study, all
      rectal cancer patients treated during 1980-2004 were included. RESULTS: More
      patients received preoperative radiotherapy during 2000-2004, but otherwise there
      were no significant differences in presentation or treatment during 1980-2004.
      The 5-year local recurrence rate after resection with curative intent was 4.5% (0
      9.7), 18.7% (10.3-27.1) and 2.2% (0-6.7) in 1980-1989, 1990-1999 and 2000-2004 (p
      = 0.006), respectively. Out of a total of 23 cases of local recurrence, treatment
      guidelines, mainly with regard to radiotherapy, were violated in 19 cases. The 5
      year overall survival after resection with curative intent was 65% (95%
      confidence interval [CI] 55-76) during 1980-1989, 58% (49-68) in 1990-1999 and
      71% (59-83) in 2000-2004 (n.s). The 5-year relative survival was 83% (95% CI 69
      95) during 1980-1989, 71% (59-81) in 1990-1999 and 84% (69-98) in 2000-2004
      (n.s). CONCLUSION: Rectal cancer patients experienced excellent outcomes in the
      period 1980-1989 and 2000-2004. Due to violations of treatment guidelines, the
      rate of local recurrence was much too high in the period 1990-1999. This article
      illustrates the importance of continuous quality assurance in the treatment of
      rectal cancer to maintain optimized outcomes for the patients.

PMID- 21861074
TI  - Clinical use of an epinephrine-reduced (1/400,000) articaine solution in short
      time dental routine treatments--a multicenter study.
AB  - The addition of epinephrine in dental local anaesthesia results in a longer and
      deeper anaesthesia under almost ischemic conditions. For short-time dental
      treatments, epinephrine-reduced anaesthetics may offer shorter and more
      individual anaesthesia with reduced potential side effects. The aim of this study
      was a clinical evaluation of anaesthetic potency and adverse effects of an
      epinephrine-reduced articaine formulation in dental patients undergoing short
      time routine treatment. In a prospective clinical, not interventional, study
      between January 2008 and February 2009, 908 patients undergoing short-time dental
      treatment in five medical centers were anaesthetized with 4% articaine 1:400,000
      epinephrine (Ubistesin, 3M/ESPE, Seefeld, Germany). Efficacy and safety in
      clinical use were evaluated. A follow-up after 1 day was conducted by telephone
      survey. A mean amount of 1.3-ml anaesthetic solution was needed to achieve a
      complete or sufficient anaesthesia in 97% (n = 876) of cases. A second injection
      had to be done in 3.7% (n = 34) before and in 11.9% (n = 108) during treatment.
      Here, the second injection had to be applied after a mean of 48.6 min. The mean
      duration of soft tissue anaesthesia after infiltration was 146.6 min, after nerve
      block 187.7 min. The painful treatment took a mean of 50.2 min and the total
      treatment time summed up to 68.8 min. In 1.7% cases (n = 15), unwanted side
      effects were observed. The results indicate that a lower concentration of
      epinephrine in combination with the 4% articaine solution leads to a high success
      rate of efficacy. The clinical use of a 4% articaine 1:400,000 epinephrine
      solution can be stated as safe and effective in short dental routine treatments.
      Reconsiderations concerning limitations of indication or additional
      contraindications are not necessary.

PMID- 21861075
TI  - Internal organs, integral selves, and good communities: opt-out organ procurement
      policies and the 'separateness of persons'.
AB  - Most people accept that if they can save someone from death at very little cost
      to themselves, they must do so; call this the 'duty of easy rescue.' At least for
      many such people, an instance of this duty is to allow their vital organs to be
      used for transplantation. Accordingly, 'opt-out' organ procurement policies,
      based on a powerfully motivated responsibility to render costless or very low
      cost lifesaving aid, would seem presumptively permissible. Counterarguments
      abound. Here I consider, in particular, objections that assign a moral
      distinctiveness to the physical boundaries of our bodies and that concern
      autonomy and trust. These objections are singled out as they seem particularly
      pertinent to the stress I place on a distinctive benefit of the particular policy
      I defend. An opt-out system, resting not on the authority of 'presumed consent'
      but on the recognition of a duty to one another, has the prospect of prompting
      people to understand more richly the ways in which they are both physically
      embodied and communally embedded.

PMID- 21861076
TI  - An approach to architecture 3D scaffold with interconnective microchannel
      networks inducing angiogenesis for tissue engineering.
AB  - The angiogenesis of 3D scaffold is one of the major current limitations in
      clinical practice tissue engineering. The new strategy of construction 3D
      scaffold with microchannel circulation network may improve angiogenesis. In this
      study, 3D poly(D: ,L: -lactic acid) scaffolds with controllable microchannel
      structures were fabricated using sacrificial sugar structures. Melt drawing sugar
      fiber network produced by a modified filament spiral winding method was used to
      form the microchannel with adjustable diameters and porosity. This fabrication
      process was rapid, inexpensive, and highly scalable. The porosity, microchannel
      diameter, interconnectivity and surface topographies of the scaffold were
      characterized by scanning electron microscopy. Mechanical properties were
      evaluated by compression tests. The mean porosity values of the scaffolds were in
      the 65-78% and the scaffold exhibited microchannel structure with diameter in the
      100-200 MUm range. The results showed that the scaffolds exhibited an adequate
      porosity, interconnective microchannel network, and mechanical properties. The
      cell culture studies with endothelial cells (ECs) demonstrated that the scaffold
      allowed cells to proliferate and penetrate into the volume of the entire
      scaffold. Overall, these findings suggest that the fabrication process offers
      significant advantages and flexibility in generating a variety of non-cytotoxic
      tissue engineering scaffolds with controllable distributions of porosity and
      physical properties that could provide the necessary physical cues for ECs and
      further improve angiogenesis for tissue engineering.

PMID- 21861077
TI  - Clinical pathologic conference case 4: hylanizing clear cell carcinoma.

PMID- 21861078
TI  - Clinical pathologic conference case 1: Wegener's granulomatosis.

PMID- 21861079
TI  - Clinical pathologic conference case 3: nodular fasciitis.
AB  - Intraoral nodular nodular fasciitis is a rare entity that is important to
      recognize because it may simulate a malignancy clinically and histologically. The
      rapid growth and high mitotic index seen in nodular fasciitis may suggest a
      malignant neoplastic process, but it is generally considered to be a benign
      reactive proliferation. Recognizing the unique histologic features of nodular
      fasciitis is important to avoid a possible misdiagnosis as a malignancy, leading
      to unnecessary further treatment.

PMID- 21861081
TI  - Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance
      imaging findings.
AB  - INTRODUCTION: Most enterovirus (EV) 71 infections manifest as mild cases of hand
      foot-mouth disease (HFMD)/herpangina with seasonal variations, having peak
      incidence during the summer. Meanwhile, EV 71 may involve the central nervous
      system (CNS), causing severe neurologic disease. In many cases, enteroviral
      encephalomyelitis involves the central midbrain, posterior portion of the medulla
      oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral
      roots of the cervical spinal cord, and the lesions show hyperintensity on T2
      weighted and fluid-attenuation inversion recovery (FLAIR) images. Our goal was to
      review usual and unusual magnetic resonance (MR) findings in CNS involvement of
      enteroviral infection. METHODS: Among consecutive patients who had HFMD and
      clinically suspected encephalitis or myelitis and who underwent brain or spinal
      MR imaging, five patients revealed abnormal MR findings. Diffusion-weighted and
      conventional MR and follow-up MR images were obtained. From cerebrospinal fluid,
      stool, or nasopharyngeal swabs, EV 71 was confirmed in all patients. RESULTS: MR
      imaging studies of two patients showed hyperintensity in the posterior portion of
      the brainstem on T2-weighted and FLAIR images, which is the well-known MR finding
      of EV 71 encephalitis. The remaining three cases revealed unusual manifestations:
      leptomeningeal enhancement, abnormal enhancement along the ventral roots at the
      conus medullaris level without brain involvement, and hyperintensity in the left
      hippocampus on T2/FLAIR images. CONCLUSION: EV 71 encephalomyelitis shows
      relatively characteristic MR findings; therefore, imaging can be helpful in
      radiologic diagnosis. However, physicians should also be aware of unusual
      radiologic manifestations of EV 71.

PMID- 21861082
TI  - Molecular analysis of the biomass of a fluidized bed reactor treating synthetic
      vinasse at anaerobic and micro-aerobic conditions.
AB  - The microbial communities (Bacteria and Archaea) established in an anaerobic
      fluidized bed reactor used to treat synthetic vinasse (betaine, glucose, acetate,
      propionate, and butyrate) were characterized by denaturing gradient gel
      electrophoresis (DGGE) and phylogenetic analysis. This study was focused on the
      competitive and syntrophic interactions between the different microbial groups at
      varying influent substrate to sulfate ratios of 8, 4, and 2 and anaerobic or
      micro-aerobic conditions. Acetogens detected along the anaerobic phases at
      substrate to sulfate ratios of 8 and 4 seemed to be mainly involved in the
      fermentation of glucose and betaine, but they were substituted by other sugar or
      betaine degraders after oxygen application. Typical fatty acid degraders that
      grow in syntrophy with methanogens were not detected during the entire reactor
      run. Likely, sugar and betaine degraders outnumbered them in the DGGE analysis.
      The detected sulfate-reducing bacteria (SRB) belonged to the hydrogen-utilizing
      Desulfovibrio. The introduction of oxygen led to the formation of elemental
      sulfur (S(0)) and probably other sulfur compounds by sulfide-oxidizing bacteria
      (gamma-Proteobacteria). It is likely that the sulfur intermediates produced from
      sulfide oxidation were used by SRB and other microorganisms as electron
      acceptors, as was supported by the detection of the sulfur respiring Wolinella
      succinogenes. Within the Archaea population, members of Methanomethylovorans and
      Methanosaeta were detected throughout the entire reactor operation.
      Hydrogenotrophic methanogens mainly belonging to the genus Methanobacterium were
      detected at the highest substrate to sulfate ratio but rapidly disappeared by
      increasing the sulfate concentration.

PMID- 21861080
TI  - Factors predicting retreatment and residual aneurysms at 1 year after
      endovascular coiling for ruptured cerebral aneurysms: Prospective Registry of
      Subarachnoid Aneurysms Treatment (PRESAT) in Japan.
AB  - INTRODUCTION: Endovascular treatment of cerebral aneurysms includes follow-up
      imaging to identify aneurysms that may need retreatment. The aim of this study
      was to determine predictors of incomplete aneurysm occlusion at 1 year after
      endovascular coiling for ruptured cerebral aneurysms. METHODS: In 129 patients of
      the Prospective Registry of Subarachnoid Aneurysms Treatment cohort, ruptured
      aneurysms were coiled within 14 days of onset and both initial post-coiling and 1
      year follow-up digital subtraction angiography or magnetic resonance angiography
      were obtained. Factors predicting 1-year incomplete aneurysm occlusion
      (retreatment within 1-year or residual aneurysms at 1 year) were determined using
      multivariate logistic regression analyses. RESULTS: One-year incomplete aneurysm
      occlusion was identified in 59 patients, including ten patients who were
      retreated within 1-year post-coiling. Dome size >=7.5 mm (P = 0.007, odds ratio
      (OR) = 5.00, 95% confidence interval (CI) = 1.55-16.15), pre-treatment aneurysm
      re-rupture (P = 0.023, OR = 3.50, 95% CI = 1.19-10.31), non-small size/small neck
      aneurysm (dome size, >=10 mm or neck size, >=4 mm; P = 0.022, OR = 3.26, 95% CI =
      1.19-8.96), and residual aneurysms on immediate post-coiling angiograms (P =
      0.017, OR = 1.43, 95% CI = 1.07-1.93) significantly predicted incomplete aneurysm
      occlusion at 1-year post-coiling. CONCLUSIONS: In addition to the characteristics
      of aneurysm and initially incomplete aneurysm occlusion, this study showed pre
      treatment aneurysm re-rupture to be a predictor that favors closer imaging follow
      ups for coiled aneurysms.

PMID- 21861083
TI  - Three dimensional spectral domain optical coherence tomography features of
      retinal-choroidal anastomosis.
AB  - BACKGROUND: To correlate the three-dimensional (3D) spectral-domain optical
      coherence tomography (SD-OCT) features of retinal-choroidal anastomosis (RCA) to
      conventional angiography. METHODS: This is a retrospective chart review of
      consecutive patients diagnosed with RCA who underwent 3D SD-OCT between July 2007
      and June 2010. Main outcome measures were the diagnostic capabilities of 3D SD
      OCT, and the correlation between 3D findings and the features distinguished by
      conventional angiography. RESULTS: Eighteen eyes of 18 patients [five males, 13
      females, mean age 79.5 +/- 19.4 years (range, 70-93 years)] were included in the
      analysis. In eyes (n = 3) showing a focal staining on angiography, 3D OCT
      revealed a slight convex prominence of the inner retinal surface in
      correspondence of a small dome-shaped retinal pigment epithelium (RPE) elevation
      (which represented the early RCA). In eyes (n = 7) showing a "hot spot" without
      pigment epithelium detachment (PED) on angiography, 3D OCT revealed a convex
      prominence of the inner retinal surface in correspondence with a well-demarcated
      prominence of RPE with steep margins (which represented the RCA). In eyes (n = 8)
      showing a "hot spot" with PED on angiography, 3D OCT revealed a convex prominence
      of the inner retinal surface in correspondence with a convex RPE prominence with
      a peak at the top. CONCLUSIONS: 3D SD-OCT provides a map of the retina and RPE,
      allowing a realistic visualization of the different pathological features in the
      disease development, and may be able to provide clinically relevant information
      to complement angiography in the diagnosis of RCA.

PMID- 21861084
TI  - Anterior chamber migration of dexametasone intravitreal implant (Ozurdex(r)).

PMID- 21861085
TI  - Astigmatism and optical coherence tomography measurements.
AB  - BACKGROUND: To evaluate the effect of astigmatism change on measurement of
      retinal nerve fiber layer (RNFL) and macular thickness by Cirrus HD spectral
      domain optical coherence tomography (Cirrus HD OCT; Carl Zeiss Meditec, Dublin,
      CA, USA). METHODS: A total of 30 right eyes from 30 healthy young subjects
      underwent RNFL and macular thickness measurements using Cirrus HD OCT.
      Measurements were performed at the baseline state and induced with-the-rule (WTR)
      and against-the-rule (ATR) astigmatism states by wearing toric soft contact
      lenses (+1.50 -3.25 diopter * 90 degrees  and +1.50 -3.25 diopter * 180 degrees 
      respectively). Differences in RNFL and macular thickness between the baseline
      state and induced astigmatism states were analyzed. RESULTS: Wearing toric soft
      contact lenses induced a mean 2.92 diopter WTR and 3.18 diopter ATR astigmatism
      respectively. After signal strength change adjustment, RNFL thicknesses of
      average, superior quadrant, 12 and 6 o'clock hour sectors decreased after
      induction of a WTR astigmatism (mean difference range, 1.58 to 6.88 MUm); RNFL
      thicknesses of average, nasal, temporal quadrants, 2, 3, and 9 o'clock hour
      sectors decreased after induction of an ATR astigmatism (mean difference range,
      0.75 to 5.11 MUm) (all P values <0.05). Macular thickness was not significantly
      affected by astigmatism changes (all P values >= 0.250). CONCLUSION: Although the
      amount of change was not substantial, RNFL thickness measured by Cirrus HD OCT
      was affected by astigmatism changes induced by contact lenses. It may be
      warranted to consider the effect of astigmatism on RNFL thickness measured by OCT
      in eyes with higher degrees of astigmatism.

PMID- 21861086
TI  - Histological findings of failed gold micro shunts in primary open-angle glaucoma.
AB  - BACKGROUND: To describe the histological features of failed gold micro shunts
      (GMS) in unsuccessful implantations for refractory primary open-angle glaucoma
      (POAG). METHODS: This was an interventional case series study. Five eyes of five
      glaucomatous patients with unsuccessful GMS implantation underwent shunt removal.
      Each device was sectioned into three portions: proximal or anterior chamber (AC)
      portion, middle or scleral portion and distal or suprachoroidal (SC) portion. The
      histological analysis was performed throughout the whole extent of the shunt,
      describing both the inner spaces and the outer surface. RESULTS: At the moment of
      removal all devices were correctly located into the SC space and in AC, with the
      exception of a case presenting corneal endothelial contact. The mean intra-ocular
      pressure before GMS removal was 30.4 +/- 5.3 mmHg, and the mean time of GMS
      removal after implantation was 6.8 +/- 2.5 months. No significant histological
      differences were documented among the five analyzed devices. The main feature was
      the presence of a thick connective capsule-like reaction surrounding both the
      proximal and distal ends and invading the posterior and anterior grid holes,
      whereas a more loosely arranged connective tissue was observed within the inner
      channels. Signs of surface fibrosis of the middle-scleral portion and
      inflammatory cell infiltration of the device were not documented in any of the
      cases. CONCLUSIONS: Failed GMS implantations presented connective tissue filling
      all the inner spaces and creating a thick fibrotic capsule surrounding the ends
      of the device. This modification isolated the GMS from the AC and SC space,
      impeding aqueous flows throughout the shunt.

PMID- 21861087
TI  - Development of surgical techniques for implantation of a wireless intraocular
      epiretinal retina implant in Gottingen minipigs.
AB  - BACKGROUND: The aim of this study was to develop surgical methods for the
      implantation of a wireless intraocular epiretinal retina implant (EPI RET3) in
      Gottingen minipigs. This animal model resembles closely the anatomical conditions
      in humans, and is thus suitable for investigating the EPI RET3 implant as
      designed for the application in humans. METHODS: Phacoemulsification and
      vitrectomy was performed on the right eye of 16 Gottingen minipigs under general
      anesthesia. The implants, consisting of a receiver module and an electrode array
      connected via a flexible micro cable, were inserted through a corneoscleral
      incision. The receiver module was placed into the sulcus ciliaris and the
      electrode array was fixed onto the retina temporal to the optic disc with a
      retinal tack. Minipigs were monitored for intra- and postoperative ocular
      complications. Follow-up times were 3 (seven minipigs) and 12 weeks (nine
      minipigs). RESULTS: Implantation was successfully performed in all 16 minipigs.
      The complete implantation surgery required on average 2 hours. Intraoperative
      findings were a minor hemorrhage of the anterior chamber angle in two eyes, one
      minor iris hemorrhage, and one minor punctiform retinal hemorrhage, which were
      all reversible. Postoperatively, the corneoscleral incision showed good wound
      healing in all eyes. Intraocular reactions included mainly fibrin exudation (six
      eyes) and formation of iris synechiae with the receiver module of the implants
      (three eyes). CONCLUSIONS: The performed implantation procedures of the
      intraocular EPI RET3 implant are feasible and reproducible within an acceptable
      surgical time. The development of inflammatory responses is a specific
      predisposition of the minipig following any intraocular intervention;
      nevertheless, the surgical techniques should be further improved to minimize
      procedure-related reactions. Our results provide a step towards the application
      of the EPI RET3 system in clinical studies.

PMID- 21861088
TI  - Treatment of intractable skin ulcers caused by vascular insufficiency with
      allogeneic cultured dermal substitute: a report of eight cases.
AB  - Chronic leg ulcers have various causes and can be difficult to treat, although
      topical treatments, including basic fibroblast growth factor and PGE1, have been
      used. We applied an allogeneic cultured dermal substitute (CDS) to eight patients
      with intractable ulcers. The patients had various underlying diseases, including
      diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome,
      necrobiosis lipoidica, stasis dermatitis, livedo vasculopathy, and rheumatoid
      arthritis. The CDS was prepared by seeding cultured human fibroblasts on a spongy
      matrix consisting of hyaluronic acid and atelocollagen. Good clinical results
      were achieved, as demonstrated by reepithelization, healthy granulation tissue
      formation, and a subsequent decrease in wound size. Daily dressing changes became
      unnecessary when the allogeneic CDS was used. Based on these results, we suggest
      that CDS may be useful for the treatment of intractable skin ulcers.

PMID- 21861089
TI  - Cardiovascular MRI without sedation or general anesthesia using a feed-and-sleep
      technique in neonates and infants.
AB  - BACKGROUND: MRI in small children generally necessitates the use of general
      anesthesia. OBJECTIVE: We describe our initial results with a new technique that
      we name the feed-and-sleep method, whereby an infant can undergo a cardiac MRI
      without the need for general anesthesia or sedation. MATERIALS AND METHODS: The
      infant is fasted for 4 h prior to the scan and is then fed by his mother prior to
      the scan. He is then swaddled with 1 to 2 infant sheets before being placed in a
      vacuum-bag immobilizer. As air is removed from the bag, the immobilizer becomes a
      rigid cradle that fits the infant's body. We prioritize the sequences according
      to the purpose of the study and in the order of clinical importance. RESULTS:
      Between January 2010 and January 2011 a total of 20 infants with the median age
      14.5 days (minimum 2 days, maximum 155 days) underwent CMR studies via this
      method. All were performed successfully with no distress to the infant. The
      median scan time was 46.5 min (minimum 20, maximum 66). All had complex
      congenital heart defects and all planned sequences were acquired with sufficient
      quality to allow accurate diagnosis and to plan appropriate surgery. CONCLUSION:
      Using this technique, infants younger than 6 months can complete a cardiovascular
      MRI without the need for sedation or general anesthesia. We advocate the
      incorporation of this safe and reliable technique into routine clinical practice.

PMID- 21861090
TI  - Suppression of interleukin 17 production by Brazilian propolis in mice with
      collagen-induced arthritis.
AB  - Propolis is a resinous substance collected by honeybees from leaf buds and cracks
      in the bark of various plants. Propolis has been reported to have
      immunomodulatory activity. We hypothesized that propolis would be able to reduce
      the disease severity of rheumatoid arthritis. We evaluated the effect of
      Brazilian propolis ethanolic extract on the pathogenesis of collagen-induced
      arthritis (CIA) in mice. Mice fed propolis exhibited significant lower clinical
      arthritis scores than those fed the control diet. To investigate the mechanism of
      the effect of propolis on CIA mice, we examined interleukin-17 (IL-17) production
      in CIA mice fed propolis using an enzyme-linked immunospot assay and flow
      cytometric analysis. The numbers of IL-17-producing cells in the CIA mice fed
      propolis were significantly decreased. To determine direct influence of propolis
      on cytokine production, splenocytes were stimulated with phorbol myristate
      acetate in the presence of propolis extract in vitro. Concentration-dependent
      declines in IL-17 expression were observed by ELISA and real-time PCR methods. We
      further found that propolis significantly inhibited the differentiation of Th17
      cells from murine splenocytes in a concentration-dependent manner. Taken
      together, our results may provide a new light on the potential mechanism of the
      immunosuppressive and anti-inflammatory effects of propolis.

PMID- 21861091
TI  - Shedding light on class-specific wiring: development of intrinsically
      photosensitive retinal ganglion cell circuitry.
AB  - Neural circuits associated with retinal ganglion cells have long been used as
      models for investigating the mechanisms that govern circuit development and
      function. Similar to neurons in the brain, retinal ganglion cells are subdivided
      into distinct classes based upon their morphology, physiology, and patterns of
      connectivity. Newly developed transgenic tools in which individual classes of
      retinal ganglion cells are labeled with reporter proteins have recently provided
      a method to study the development of their class-specific circuitry. Here, we
      examine a single class of intrinsically photosensitive retinal ganglion cells and
      discuss their class-specific circuitry, as well as the cellular and molecular
      mechanisms that govern assembly of this circuitry.

PMID- 21861093
TI  - Feasibility study and control values of transient elastography in healthy
      children.
AB  - Transient elastography (TE) is a new technique for the non-invasive assessment of
      liver fibrosis. The degree of fibrosis is equivalent to the liver stiffness
      measured in kilopascal (kPa). It is frequently used in adult patients with a mean
      normal stiffness of 4.4-5.5 kPa. Since 2008, liver stiffness can be measured even
      in small children and infants following the availability of a new probe with a
      smaller diameter (S-probe 5 mm) than the regular probe (M-probe 7 mm). We report
      control values for healthy children between 0 and 18 years and investigated the
      feasibility of this technique in a pediatric population. For control values, TE
      was performed in infants and children after exclusion of liver disease by medical
      history, clinical examination, blood investigation, and abdominal ultrasound. For
      feasibility analyses the results of all TE performed in our clinic were analyzed
      irrespective of the underlying disease. Liver stiffness was measured with the S
      probe (thorax diameter <45 cm (S1) or 45-75 cm (S2)) and the M-probe (thorax
      diameter >75 cm) according to the manufacturer's recommendations. A total of 240
      healthy children were analyzed to establish control values. The median liver
      stiffness was 4.7 kPa resulting in an upper limit of normal of 6.47 kPa. Median
      values of stiffness were significantly age dependent with 4.40, 4.73, and 5.1 kPa
      in children 0-5, 6-11, and 12-18 years (p = 0.001) while the interquartile range
      decreased with age (0.8, 0.7, and 0.6 kPa). The resulting upper limit of normal
      (median plus 1.64 times standard deviation) was 5.96, 6.65, and 6.82 kPa. Girls
      between 11 and 18 years showed a significantly lower median stiffness than boys
      of the same age (4.7 vs. 5.6 kPa; p < 0.005). Feasibility was tested in 975
      consecutive liver stiffness measurements (LSM) in children 0-18 years of age.
      Patients with invalid LSM were significantly younger than those with valid LSM
      (5.8 vs. 9.7 years, p < 0.0001), showed a significantly higher stiffness (10.2
      vs. 6.17, p < 0.0001), and examinations took significantly longer (202 vs. 160 s,
      p < 0.0001). TE is technically possible in children of all age groups. The upper
      limit of normal increases significantly with age. Due to movement artifacts the
      measurement is reliable from the age of 6 without sedation. In younger children
      the number of invalid measurements increases significantly. Further studies are
      needed to asses the value of TE in the diagnosis and follow-up of liver disease
      in pediatric hepatology.

PMID- 21861092
TI  - How histone deacetylases control myelination.
AB  - Myelinated axons are a beautiful example of symbiotic interactions between two
      cell types: Myelinating glial cells organize axonal membranes and build their
      myelin sheaths to allow fast action potential conduction, while axons regulate
      myelination and enhance the survival of myelinating cells. Axonal demyelination,
      occurring in neurodegenerative diseases or after a nerve injury, results in
      severe motor and/or mental disabilities. Thus, understanding how the myelination
      process is induced, regulated, and maintained is crucial to develop new
      therapeutic strategies for regeneration in the nervous system. Epigenetic
      regulation has recently been recognized as a fundamental contributing player. In
      this review, we focus on the central mechanisms of gene regulation mediated by
      histone deacetylation and other key functions of histone deacetylases in Schwann
      cells and oligodendrocytes, the myelinating glia of the peripheral and central
      nervous systems.

PMID- 21861094
TI  - Behavioral and molecular evidence for psychotropic effects in L-theanine.
AB  - RATIONALE: L-Theanine (N-ethyl-L: -glutamine) is an amino acid uniquely found in
      green tea and historically considered to be a relaxing agent. It is a glutamate
      derivative and has an affinity for glutamatergic receptors. However, its
      psychotropic effects remain unclear. OBJECTIVES: To elucidate effects of L: 
      theanine on psychiatric disease-related behaviors in mice and its molecular basis
      focusing on brain-derived neurotrophic factor (BDNF) and N-methyl-D: -aspartate
      (NMDA) receptor. METHODS: We examined the effects of L: -theanine on behaviors in
      mice by using the open-field test (OFT), forced swim test (FST), elevated plus
      maze test (EPMT), and prepulse inhibition (PPI) of acoustic startle. By western
      blot analysis, we looked at the effect of L: -theanine on the expression of BDNF
      and related proteins in the hippocampus and cerebral cortex. To determine whether
      L: -theanine has agonistic action on the NMDA receptor, we performed Fluo-3
      intracellular Ca(2+) imaging in cultured cortical neurons. RESULTS: Single
      administration of L: -theanine significantly attenuated MK-801-induced deficits
      in PPI. Subchronic administration (3-week duration) of L: -theanine significantly
      reduced immobility time in the FST and improved baseline PPI. Western blotting
      analysis showed increased expression of BDNF protein in the hippocampus after
      subchronic administration of L: -theanine. In cultured cortical neurons, L: 
      theanine significantly increased the intracellular Ca(2+) concentration, and this
      increase was suppressed by competitive and non-competitive NMDA receptor
      antagonists (AP-5 and MK-801, respectively). CONCLUSIONS: Our results suggest
      that L: -theanine has antipsychotic-like and possibly antidepressant-like
      effects. It exerts these effects, at least in part, through induction of BDNF in
      the hippocampus and the agonistic action of L: -theanine on the NMDA receptor.

PMID- 21861095
TI  - The role of conditioning history and reinforcer strength in the reinforcement
      enhancing effects of nicotine in rats.
AB  - RATIONALE: Nicotine (NIC) administration can increase behaviors that result in
      delivery of non-drug reinforcers (e.g., salient sensory stimuli). However, little
      is known about the circumstances under which NIC increases these behaviors.
      OBJECTIVE: The present studies sought to extend the reinforcement enhancing
      effects of NIC to sucrose rewards for which intensity could be systematically
      manipulated. METHOD: In Experiment 1, rats were trained to respond for sucrose
      (30% w/v) on a progressive ratio (PR) schedule of reinforcement and were
      pretreated with NIC (0.4 mg/kg free-base) or physiological saline (SAL). The
      intensity of the sucrose reward was manipulated over subsequent testing sessions
      (0-60% w/v). Similar procedures were used in Experiment 2; however, each subject
      received only one sucrose concentration (0-20%) to control for conditioning
      history. In Experiment 3, a fixed ratio 3 (FR3) schedule of reinforcement was
      used to investigate putative activating effects of NIC. Experiment 4 investigated
      whether NIC pretreatment would reduce sucrose intake in limited-access drinks.
      RESULTS: In Experiment 1, NIC increased the motivation to obtain all sucrose
      concentrations, including water. However, when conditioning history was
      controlled (Experiment 2) the reinforcement enhancing effects of NIC were
      systematically related to the strength of the reinforcer. In Experiment 3, NIC
      neither increased nor decreased responding for sucrose. In Experiment 4, NIC
      reduced sucrose intake, but only at concentrations that resulted in peak drink
      volumes (5-20%). CONCLUSION: The results suggest that the reinforcement enhancing
      effects of NIC depend on conditioning history and do not appear to be the result
      of simple behavioral activation.

PMID- 21861096
TI  - Late-onset intermittent fasting dietary restriction as a potential intervention
      to retard age-associated brain function impairments in male rats.
AB  - Lifelong dietary restriction (DR) is known to have many potential beneficial
      effects on brain function as well as delaying the onset of neurological diseases.
      In the present investigation, the effect of late-onset short-term intermittent
      fasting dietary restriction (IF-DR) regimen was studied on motor coordination and
      cognitive ability of ageing male rats. These animals were further used to
      estimate protein carbonyl content and mitochondrial complex I-IV activity in
      different regions of brain and peripheral organs, and the degree of age-related
      impairment and reversion by late-onset short-term IF-DR was compared with their
      levels in 3-month-old young rats. The results of improvement in motor
      coordination by rotarod test and cognitive skills by Morris water maze in IF-DR
      rats were found to be positively correlated with the decline in the oxidative
      molecular damage to proteins and enhanced mitochondrial complex IV activity in
      different regions of ageing brain as well as peripheral organs. The work was
      further extended to study the expression of synaptic plasticity-related proteins,
      such as synaptophysin, calcineurin and CaM kinase II to explore the molecular
      basis of IF-DR regimen to improve cognitive function. These results suggest that
      even late-onset short-term IF-DR regimen have the potential to retard age
      associated detrimental effects, such as cognitive and motor performance as well
      as oxidative molecular damage to proteins.

PMID- 21861097
TI  - Cognitive impairment in Huntington disease: diagnosis and treatment.
AB  - Cognition has been well characterized in the various stages of Huntington disease
      (HD) as well as in the prodrome before the motor diagnosis is given. Although the
      clinical diagnosis of HD relies on the manifestation of motor abnormalities, the
      associated impairments have been growing in prominence for several reasons.
      First, research to understand the most debilitating aspects of HD has suggested
      that cognitive and behavioral changes place the greatest burden on families, are
      most highly associated with functional decline, and can be predictive of
      institutionalization. Second, cognitive impairments are evident at least 15 years
      prior to the time at which motor diagnosis is given. Finally, cognitive decline
      is associated with biological markers such as brain atrophy, circulating levels
      of brain-derived neurotrophic factors, and insulin-like growth factor 1. Efforts
      are now underway to develop valid and reliable measures of cognition in the
      prodrome as well as in all stages of HD so that clinical trials can be conducted
      using cognitive outcomes.

PMID- 21861099
TI  - Melatonin for migraine prevention.

PMID- 21861098
TI  - Tension-type headache and systemic medical disorders.
AB  - Tension-type headache (TTH) is the most common form of headache in the general
      population. Diagnosis of TTH is based merely on clinical features and on careful
      exclusion of all possible causes of headache. Most of the headaches that present
      in the context of medical disorders (e.g., hypothyroidism, sleep disorders, and
      hypertensive crisis) have clinical features overlapping with those of TTH;
      medical history and specific features of the systemic disorder are usually the
      clues to establish a correct diagnosis. Some medical disorders may worsen a
      preexisting TTH, and is also possible the comorbidity of TTH with psychiatric
      disorders and fibromyalgia.

PMID- 21861100
TI  - Successful bone reconstruction after bortezomib therapy in a myeloma patient.

PMID- 21861101
TI  - Effects of zoledronic acid on bone mineral density during aromatase inhibitor
      treatment of Korean postmenopausal breast cancer patients.
AB  - The age distribution of breast cancer patients in Korea, where most are less than
      60 years of age and have recently entered menopause, differs from that in the
      West. The aim of this study was to evaluate bone mineral density (BMD) changes in
      Korean breast cancer patients treated with an aromatase inhibitor (AI) either
      alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar
      spine and hip were evaluated in 107 patients receiving AI treatment, of which 59
      were treated in combination with ZA. The mean age of the patients was 54.9 years,
      and the median follow-up period was 38.2 months. With AI treatment alone, BMD
      loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18
      and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and
      6.82%) after treatment. In contrast, the combination treatment resulted in
      increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%,
      respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after
      treatment. BMD loss in the lumbar spine was significantly greater in AI alone
      treated women who had entered menopause within the past year compared with those
      who had entered menopause more than 1 year ago, when measured 12 and 24 months
      after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively
      inhibited AI-associated bone loss, independent of the postmenopausal interval.
      Because the proportion of patients in this study who had recently entered
      menopause was high, bone loss in Korean breast cancer patients treated with AI
      alone was higher than data reported from the Arimidex, Tamoxifen Alone or in
      Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective
      in preventing AI-induced bone loss in Korean postmenopausal breast cancer
      patients.

PMID- 21861102
TI  - Structure-function analysis of the beta regulatory subunit of protein kinase CK2
      by targeting embryonic stem cell.
AB  - Programs that govern stem cell maintenance and pluripotency are dependent on
      extracellular factors and of intrinsic cell modulators. Embryonic stem (ES) cells
      with a specific depletion of the gene encoding the regulatory subunit of protein
      kinase CK2 (CK2beta) revealed a viability defect. However, analysis of CK2beta
      functions along the neural lineage established CK2beta as a positive regulator
      for neural stem/progenitor cell (NSC) proliferation and multipotency. By using an
      in vitro genetic conditional approach, we demonstrate in this work that specific
      domains of CK2beta involved in the regulatory function towards CK2 catalytic
      subunits are crucial structural determinants for ES cell homeostasis.

PMID- 21861103
TI  - Selective expression of S100A11 in lung cancer and its role in regulating
      proliferation of adenocarcinomas cells.
AB  - S100A11, one secreted protein, is overexpressed in certain cancers. We
      investigated S100A11 expression in various subtypes of lung cancer and explored
      its role in cell proliferation. S100A11 mRNA level was examined in 45 pairs of
      frozen lung cancer tissues by reverse transcriptase PCR (RT-PCR). The specific
      expression and subcellular distribution of S100A11 were examined in 78 paraffin
      embedded lung cancers, 2 benign lung diseases as well as 22 healthy lung tissues
      by immunohistochemistry. S100A11 protein level was further analyzed in the sera
      of 86 lung cancer patients and 50 healthy individuals by enzyme-linked
      immunosorbent assay. We found that both mRNA and protein levels of S100A11 were
      overexpressed in adenocarcinomas (ADC) and squamous cell carcinomas (SCC)
      compared with paired non-cancerous lung tissues, while S100A11 was detected
      downregulated in small cell lung cancers (SCLC). Further immunohistochemistry
      staining was positive for S100A11 only in non-small cell lung cancer (NSCLC)
      (ADC, SCC, large cell carcinomas, et al.), but not SCLC. Conclusively, we found
      S100A11 protein level increased in the sera of NSCLC patients. Furthermore, when
      S100A11 expression was knocked down in lung adenocarcinoma cells A549 and LTEP-a
      2, the cell proliferation was significantly inhibited in vitro and in vivo.

PMID- 21861105
TI  - Barriers to screening for hepatitis B virus infection in Asian Americans.
AB  - BACKGROUND: Routine screening for hepatitis B virus (HBV) infection can identify
      individuals who need vaccination or treatment, as vaccination can prevent HBV
      infection. Although the overall prevalence of HBV infection in the United States
      is low (<1%), it is high (~10%) in Asian Americans. However, HBV screening rates
      in this population have been reported to be low. AIMS: This article systemically
      reviews the reported prevalence of HBV infection, the rate of HBV screening and
      access to HBV care, barriers for HBV screening and care, and a possible approach
      for improving HBV screening in Asian Americans. METHODS: Articles published from
      1999 to 2011 on HBV screening and disparity in Asian Americans were identified by
      searching electronic databases (PubMed and Cochrane Library), and reviewed.
      RESULTS: Published studies, including a recent report from the Institute of
      Medicine of the National Academies, revealed HBV screening rates are low in Asian
      Americans. This review addresses the need for HBV screening in Asian Americans.
      Barriers to HBV screening are related to patients, providers, and/or the
      healthcare system. Screening programs that incorporate culturally sensitive
      interventions and include educational outreach, vaccination, and a link to
      healthcare services improve rates of HBV screening and vaccination in this at
      risk community. CONCLUSIONS: A strategy that integrates efforts from the
      healthcare profession, federal agencies, and the community will be needed to
      improve HBV screening and access to HBV care for Asian Americans.

PMID- 21861106
TI  - Mechanism of action of 1,25-dihydroxyvitamin D3 on intestinal calcium absorption.
AB  - 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is the major controlling hormone of
      intestinal calcium absorption. As the body's demand for calcium increases from a
      diet deficient in calcium, from growth, pregnancy or lactation, the synthesis of
      1,25(OH)(2)D(3) is increased resulting in the stimulation of intestinal calcium
      absorption. However a complete description of the molecular mechanisms involved
      in the 1,25(OH)(2)D(3) regulated calcium absorptive process remains incomplete.
      Intestinal calcium absorption occurs by both an active saturable transcellular
      pathway and a passive nonsaturable paracellular pathway. Each step in the process
      of transcellular calcium transport (apical entry of calcium, translocation of
      calcium through the interior of the enterocyte and basolateral extrusion of
      calcium by the plasma membrane pump) has been reported to involve a vitamin D
      dependent component. This article will review recent studies, including those
      using knockout mice, that have suggested that 1,25(OH)(2)D(3) mediated calcium
      absorption is more complex than the traditional three step model of transcellular
      calcium transport. Current concepts are reviewed and questions that remain are
      addressed. Evidence for a role of 1,25(OH)(2)D(3) in the regulation of the
      paracellular pathway is also discussed.

PMID- 21861108
TI  - Animal Cognition: the next steps.

PMID- 21861107
TI  - Mechanism of action of vitamin D and the vitamin D receptor in colorectal cancer
      prevention and treatment.
AB  - Vitamin D and its analogs are potent inhibitors of colorectal cancer growth and
      metastasis. A number of recent studies have defined the intersections between the
      beta-catenin-TCF pathway (a known contributor to colorectal cancer progression)
      and the vitamin D receptor (VDR) pathway, shedding light on the underlying
      mechanisms. Vitamin D also regulates the innate immune response, and as such
      influences susceptibility to inflammatory bowel disease, a predisposing factor in
      colorectal cancer. Understanding the role of vitamin D in these different
      contexts will enable development of next generation vitamin D analogs that will
      serve as both chemopreventatives and cancer therapeutics, without the
      accompanying side effects of hypercalcemia usually associated with high vitamin D
      intake. This review summarizes the mechanisms of action of vitamin D and the VDR
      in the context of the gastrointestinal tract and colorectal carcinogenesis.

PMID- 21861109
TI  - Dogs do look at images: eye tracking in canine cognition research.
AB  - Despite intense research on the visual communication of domestic dogs, their
      cognitive capacities have not yet been explored by eye tracking. The aim of the
      current study was to expand knowledge on the visual cognition of dogs using
      contact-free eye movement tracking under conditions where social cueing and
      associative learning were ruled out. We examined whether dogs spontaneously look
      at actual objects within pictures and can differentiate between pictures
      according to their novelty or categorical information content. Eye movements of
      six domestic dogs were tracked during presentation of digital color images of
      human faces, dog faces, toys, and alphabetic characters. We found that dogs
      focused their attention on the informative regions of the images without any task
      specific pre-training and their gazing behavior depended on the image category.
      Dogs preferred the facial images of conspecifics over other categories and
      fixated on a familiar image longer than on novel stimuli regardless of the
      category. Dogs' attraction to conspecifics over human faces and inanimate objects
      might reflect their natural interest, but further studies are needed to establish
      whether dogs possess picture object recognition. Contact-free eye movement
      tracking is a promising method for the broader exploration of processes
      underlying special socio-cognitive skills in dogs previously found in behavioral
      studies.

PMID- 21861110
TI  - Unchanged muscle fiber conduction velocity relates to mild acidosis during
      exhaustive bicycling.
AB  - Muscle fiber conduction velocity (MFCV) has often been shown to decrease during
      standardized fatiguing isometric contractions. However, several studies have
      indicated that the MFCV may remain constant during fatiguing dynamic exercise. It
      was investigated if these observations can be related to the absence of a large
      decrease in pH and if MFCV can be considered as a good indicator of acidosis,
      also during dynamic bicycle exercise. High-density surface electromyography
      (HDsEMG) was combined with read-outs of muscle energetics recorded by in vivo
      (31)P magnetic resonance spectroscopy (MRS). Measurements were performed during
      serial exhausting bouts of bicycle exercise at three different workloads. The
      HDsEMG recordings revealed a small and incoherent variation of MFCV during all
      high-intensity exercise bouts. (31)P MRS spectra revealed a moderate decrease in
      pH at the end of exercise (~0.3 units down to 6.8) and a rapid ancillary drop to
      pH 6.5 during recovery 30 s post-exercise. This additional degree of
      acidification caused a significant decrease in MFCV during cycling immediately
      after the rest period. From the data a significant correlation between MFCV and
      [H(+)] ([H(+)] = 10(-pH)) was calculated (p < 0.001, Pearson's R = -0.87). Our
      results confirmed the previous observations of MFCV remaining constant during
      fatiguing dynamic exercise. A constant MFCV is in line with a low degree of
      acidification, considering the presence of a correlation between pH and MFCV
      after further increasing acidification.

PMID- 21861111
TI  - Comparison of artificial neural network (ANN) and partial least squares (PLS)
      regression models for predicting respiratory ventilation: an exploratory study.
AB  - The objective of this study was to assess the potential for using artificial
      neural networks (ANN) to predict inspired minute ventilation (V(I)) during
      exercise activities. Six physiological/kinematic measurements obtained from a
      portable ambulatory monitoring system, along with individual's anthropometric and
      demographic characteristics, were employed as input variables to develop and
      optimize the ANN configuration with respect to reference values simultaneously
      measured using a pneumotachograph (PT). The generalization ability of the
      resulting two-hidden-layer ANN model was compared with a linear predictive model
      developed through partial least squares (PLS) regression, as well as other V(I)
      predictive models proposed in the literature. Using an independent dataset
      recorded from nine 80-min step tests, the results showed that the ANN-estimated
      V(I) was highly correlated (R(2) = 0.88) with V(I) measured by the PT, with a
      mean difference of approximately 0.9%. In contrast, the PLS and other regression
      based models resulted in larger average errors ranging from 7 to 34%. In
      addition, the ANN model yielded estimates of cumulative total volume that were on
      average within 1% of reference PT measurements. Compared with established
      statistical methods, the proposed ANN model demonstrates the potential to provide
      improved prediction of respiratory ventilation in workplace applications for
      which the use of traditional laboratory-based instruments is not feasible.
      Further research should be conducted to investigate the performance of ANNs for
      different types of physical activity in larger and more varied worker
      populations.

PMID- 21861112
TI  - Cold stability of microtubules in wood-forming tissues of conifers during seasons
      of active and dormant cambium.
AB  - The cold stability of microtubules during seasons of active and dormant cambium
      was analyzed in the conifers Abies firma, Abies sachalinensis and Larix
      leptolepis by immunofluorescence microscopy. Samples were fixed at room
      temperature and at a low temperature of 2-3 degrees C to examine the effects of
      low temperature on the stability of microtubules. Microtubules were visible in
      cambium, xylem cells and phloem cells after fixation at room temperature during
      seasons of active and dormant cambium. By contrast, fixation at low temperature
      depolymerized microtubules in cambial cells, differentiating tracheids,
      differentiating xylem ray parenchyma and phloem ray parenchyma cells during the
      active season. However, similar fixation did not depolymerize microtubules during
      cambial dormancy in winter. Our results indicate that the stability of
      microtubules in cambial cells and cambial derivatives at low temperature differs
      between seasons of active and dormant cambium. Moreover, the change in the
      stability of microtubules that we observed at low temperature might be closely
      related to seasonal changes in the cold tolerance of conifers. In addition, low
      temperature fixation depolymerized microtubules in cambial cells and
      differentiating cells that had thin primary cell walls, while such low
      temperature fixation did not depolymerize microtubules in differentiating
      secondary xylem ray parenchyma cells and tracheids that had thick secondary cell
      walls. The stability of microtubules at low temperature appears to depend on the
      structure of the cell wall, namely, primary or secondary. Therefore, we propose
      that the secondary cell wall might be responsible for the cold stability of
      microtubules in differentiating secondary xylem cells of conifers.

PMID- 21861113
TI  - Light affects ascorbate content and ascorbate-related gene expression in tomato
      leaves more than in fruits.
AB  - Little is known about the light regulation of vitamin C synthesis in fruits. In
      contrast, previous studies in leaves revealed that VTC2 (coding for GDP-L: 
      galactose phosphorylase) was one of the key genes up-regulated by light in
      leaves. Our objective was to determine how the expression of ascorbate (AsA)
      synthesis genes in tomato (Solanum lycopersicum) was modified according to light
      irradiance in both leaves and fruits. Seven days of shading strongly decreased
      total ascorbate (reduced and oxidized form) content in leaves (50%) and to a
      lesser extent in fruits (10%). Among the last six steps of AsA biosynthesis, only
      two genes, VTC2 and GPP1 (one of the two unigenes coding for L: -galactose-1-P
      phosphatase in tomato), were down-regulated by long-term shading in red ripe
      fruits, compared to seven genes regulated in leaves. This underlines that light
      affects AsA-related gene expression more in leaves than in ripening fruits.
      Moreover, this study reveals strong daily changes in transcript levels of enzymes
      of the AsA biosynthetic pathway in leaves (11 of the 12 studied genes showed
      significant changes in their expression pattern). Among those genes, we found
      that diurnal variation in transcript levels of VTC2 and GME1 correlated to leaf
      AsA content measured 8 h later. This study provides a new hypothesis on the role
      of GME1 in addition to VTC2 in light-regulated AsA biosynthesis.

PMID- 21861114
TI  - Frequency of removal movements during social versus self-grooming among wild
      chimpanzees.
AB  - Grooming was observed in 11 wild chimpanzees (Pan troglodytes schweinfurthii) in
      Mahale, Tanzania, and the number of removal and stroke movements and grooming
      duration were recorded. Removal movements were more frequent during social
      grooming than during self-grooming. Chimpanzees used one or both hands for
      grooming, and grooming using both hands was more efficient for removing small
      objects. Due to physical constraints, self-grooming of the arms was almost always
      done using only one hand. The removal movement frequency during arm grooming was
      lower when self-grooming than when grooming another. They were more likely to use
      both hands during grooming another than during self-grooming, and fewer physical
      constraints during social grooming enabled a higher level of hygienic grooming.

PMID- 21861115
TI  - Feeding ecology and activity pattern of black-fronted titi monkeys (Callicebus
      nigrifrons) in a semideciduous tropical forest of southern Brazil.
AB  - Most aspects of the ecology and behavior of Callicebus nigrifrons are still
      unknown. The information available about this species is mainly based on a few
      studies that also focused on other Callicebus. We examined the feeding behavior
      and activity pattern of a free-ranging pair of C. nigrifrons between March and
      November 2007 in an area of semideciduous tropical forest of southeastern Brazil.
      The study site is located at the southern limit of the Tropical Zone and is
      characterized by pronounced seasonality. As observed for other Callicebus
      monkeys, fruits were the most consumed food resource, accounting for 53% of the
      diet, which was complemented mainly by leaves (16%) but also by invertebrates and
      flowers (10% of each). A great variety of plant families (28) and species (62)
      were included in the diet. The titis spent 35% of their time feeding,
      distributing the remaining time between resting (30%) and traveling (24%). Data
      presented here indicate that C. nigrifrons prefer high-quality food items (fruit
      pulp), adding low-quality food items (such as leaves) as the availability of the
      higher-quality foods decreases. The amount of time spent traveling and resting
      did not change between seasons, but the time invested in feeding increased during
      the lean period. The activity pattern was not related to fruit availability, but
      in months with lower temperatures, monkeys spent more time feeding. We suggest
      that the feeding ecology and activity pattern of C. nigrifrons reflect
      adaptations related to annual fluctuations in food availability and temperature,
      respectively.

PMID- 21861116
TI  - Determination of whether the association between serum albumin and activities of
      daily living in frail elderly people is causal.
AB  - OBJECTIVES: Serum albumin and activities of daily living (ADL) are associated
      with each other, but whether the association is causal is not known. The purpose
      of this study was to determine whether a causal association exists between serum
      albumin and ADL levels. METHODS: The subjects were 116 frail elderly individuals
      (34 men and 82 women; mean age 83.0 years). Demographic characteristics, serum
      albumin, ADL, and handgrip strength were measured at a baseline examination and
      at a follow-up examination 2 years later. Levels of ADL were assessed with the
      Barthel Index. Pearson's correlation coefficients were calculated for serum
      albumin, ADL, and handgrip strength for baseline values and for their 2-year
      changes (Delta). RESULTS: At baseline, the mean serum albumin concentration was
      4.0 g/dL and the total score of the Barthel Index (baseline Barthel Index) was
      71.1. The baseline serum albumin level correlated significantly with the baseline
      Barthel Index (r = 0.287) and baseline handgrip strength (r = 0.315), but not
      with Delta Barthel Index (r = 0.096) or Delta handgrip strength (r = - 0.058).
      The Delta serum albumin correlated significantly with Delta Barthel Index (r =
      0.296), but not with Delta handgrip strength (r = 0.182), baseline Barthel Index
      (r = - 0.044), or baseline handgrip strength (r = 0.047). CONCLUSIONS: This 2
      year cohort study has demonstrated that a decrease in serum albumin levels is
      associated with a decrease in ADL levels. A third factor may play a role in
      adversely affecting both serum albumin and ADL levels in frail elderly people.

PMID- 21861117
TI  - Perception of the risk of sexual transmission of HIV among Congolese and Japanese
      university students.
AB  - OBJECTIVE: Sub-Saharan Africa remains the region most heavily affected by HIV
      infection. This study aimed to evaluate the knowledge, attitudes, and practices
      of Congolese students of risk behaviors for sexual transmission of HIV in
      comparison with their Japanese counterparts. METHODS: Of the 1,747 undergraduate
      students who participated in the survey, there were 1,326 respondents (752
      Japanese, 574 Congolese) who voluntarily and fully filled out the auto
      administered questionnaire. RESULTS: The proportion of Congolese respondents who
      do not always use condoms with an occasional sex partner was significantly
      higher, 57%, as compared with their Japanese counterparts (15%; p < 0.001). Fewer
      than 40% (9.9-39.7%) of Congolese respondents had accurate knowledge about
      multiple sex partnership (MSP), men sex with men (MSM), precocious sex, and
      commercial sex work (CSW) being high-risk behaviors (p < 0.001) for the sexual
      transmission of HIV infection. However, the proportion of Congolese tested or
      willing to get tested for HIV was significantly higher (97.2%) than that in the
      Japanese group (72.4%, p < 0.001). In Congolese students, we observed an absence
      of adherence to preventive measures such as condom use with an occasional sex
      partner, and a greater proportion of students having inaccurate knowledge of
      major risk behaviors such as MSM, precocious sex, and MSP, compared with their
      Japanese counterparts. CONCLUSIONS: This study showed that, though sexual contact
      remains the main mode of HIV transmission in the region, Congolese students tend
      to have inaccurate knowledge of risk behaviors that expose people to the sexual
      transmission of HIV. This suggests that continuous education targeting those risk
      behaviors is of great importance to reduce the spread of the HIV epidemic.

PMID- 21861118
TI  - Risk factors of septic shock in bacteremic acute pyelonephritis patients admitted
      to an ER.
AB  - Our objective was to identify factors associated with septic shock in patients
      with bacteremic acute pyelonephritis who were admitted to our emergency
      department (ER). We performed a retrospective cohort study of 208 adult cases
      compiled between January 2000 and December 2010. The mean age of the 208
      predominantly female (81.3%) adult cases enrolled during the study period was
      65.9 +/- 15.2 years. The overall mortality rate was 6.7% (14/208), but the
      mortality rate of 54 patients (26%, 54/208) who initially presented with shock
      was 25.9% (14/54). Multiple logistic regression analyses revealed that the
      independent risk factors for the occurrence of septic shock were the presence of
      a urinary tract obstruction (OR 4.391, 95% CI 1.782-10.821, P = 0.001),
      healthcare-associated infection (OR 3.491, 95% CI 1.585-7.692, P = 0.002), and
      liver cirrhosis (OR 4.609, 95% CI 1.395-15.222, P = 0.012). Therefore, physicians
      should be aware that appropriate early management is necessary to prevent fatal
      outcomes in patients with risk factors of septic shock.

PMID- 21861119
TI  - Growth hormone and proopiomelanocortin are targeted by autoantibodies in a
      patient with biopsy-proven IgG4-related hypophysitis.
AB  - Hypophysitis is a chronic inflammation of the pituitary gland often caused by
      autoimmunity. Among the autoimmune diseases it is one of the few where the
      autoantigens remain to be identified. The goal of the paper was to characterize
      the antigenic profile in a previously reported patient with IgG4-related
      hypophysitis. Immunofluorescence and immunoblotting were performed to detect
      antibodies to human pituitary proteins. The proteins recognized by western
      blotting were then submitted to mass spectrometry for sequencing. The patient's
      autoantibodies recognized two unique bands around 40 and 30 kDa on
      immunoblotting. Sequencing revealed one peptide from proopiomelanocortin in the
      40 kDa band and four peptides from growth hormone in the 30 kDa band. This work
      represents the first antigenic profile in IgG4-related hypophysitis, and the
      first recognition of proopiomelanocortin as a possible pituitary autoantigen. In
      addition, the work supports previous suggestions of growth hormone as a pituitary
      autoantigen. Further studies are needed to prove the pathogenicity and diagnostic
      utility of these two pituitary proteins.

PMID- 21861120
TI  - The functional gene diversity in natural populations over postglacial areas: the
      shaping mechanisms behind genetic composition of longnose dace (Rhinichthys
      cataractae) in northeastern North America.
AB  - The diversity of functional genes and the related processes are important issues
      for conservation biology. This is especially relevant for populations that have
      suffered from demographic reduction as a consequence of the processes of
      postglacial colonization. In this perspective, the aims of the present study are
      (1) to quantify the genetic diversity of functional genes and (2) to disentangle
      the long- and short-term effects of natural selection that shapes genetic
      diversity from those of drift, mutation, and allopatric fragmentation. This
      research was conducted using an extensive genetic polymorphism analysis of
      populations of longnose dace (Rhinichthys cataractae) living over an area once
      covered by Pleistocene glaciations. The sequence and diversity of one exon of
      three genes (MHC IIbeta, growth hormone, and trypsin) were jointly analyzed with
      non-coding nuclear loci from 27 populations; these populations were sampled over
      four major basins of northeastern North America. The survey revealed a
      surprisingly low allelic richness, especially for the MHC gene, considering the
      number of individuals and populations sampled. The results suggest that there is
      a complex mixture of different evolutionary processes shaping the level of
      polymorphism among longnose dace. While our study underlines the importance of
      the short-term effects of neutral processes and the major impact of post-glacial
      colonization on gene diversity, locally dependent balancing selection was
      detected on MHC. From this perspective, our results support an understanding of
      the importance of drift on functional gene diversity but also highlight the
      transient effects of natural selection on allelic composition, even in
      populations that show drastic reduction of genetic diversity.

PMID- 21861121
TI  - Down regulation effect of Rosmarinus officinalis polyphenols on cellular stress
      proteins in rat pheochromocytoma PC12 cells.
AB  - Polyphenols are known to exhibit wide spectrum of benefit for brain health and to
      protect from several neurodegenerative diseases. The present study was sought to
      determine the neuroprotective effects of Rosmarinus officinalis' polyphenols
      (luteolin, carnosic acid, and rosmarinic acid) through the investigation of
      stress-related proteins. We carried out measurement of the expression of heat
      shock protein (Hsp) 47 promoter in heat stressed Chinese hamster ovary
      transfected cells. We performed proteomic analysis and confirmed gene expression
      by real time PCR in PC12 cells. Results showed that these compounds modulated
      significant and different effects on the expression of 4 stress-related proteins:
      heat shock protein 90 alpha (Hsp90), Transitional endoplasmic reticulum ATPase
      (VCP/p97), Nucleoside diphosphate kinase (NDK), and Hypoxia up-regulated protein
      1 (HYOU1)) at translational and post translational levels in PC12 cells and they
      downregulated the expression of Hsp47 activity in Chinese hamster transformed
      cells. These findings suggest that luteolin, carnosic acid, and rosmarinic acid
      may modulate the neuroprotective defense system against cellular stress insults
      and increase neuro-thermotolerance.

PMID- 21861122
TI  - Dual infection with Bordetella pertussis and Mycoplasma pneumoniae in three
      infants: case reports.
AB  - Studying pertussis-like respiratory infections, we report the cases of three
      infants with evidence of both Bordetella pertussis and Mycoplasma pneumoniae.
      Bordetella infection was identified by the real-time polymerase chain reaction
      (RT-PCR) of nasopharyngeal specimens. Neither B. pertussis nor B. parapertussis
      were recovered on the culture of nasopharyngeal aspirates (NPAs) from any
      subjects. M. pneumoniae etiology was diagnosed by culture and RT-PCR. The
      evolution was fatal for all of the subjects. We conclude that, among patients
      with Bordetella infection, co-infection with another respiratory pathogen is
      often probable, and these mixed infections might cause a more severe form of
      illness, sometimes leading to death.

PMID- 21861123
TI  - Retroperitoneal abscesses due to Nocardia farcinica: report of two cases in
      patients with malnutrition.

PMID- 21861124
TI  - Management of hyperglycemia in acute ischemic stroke.
AB  - OPINION STATEMENT: There is considerable clinical evidence that hyperglycemia at
      the onset of acute ischemic stroke may negatively impact not only acute morbidity
      but also brain recovery. Establishing hyperglycemia treatment protocols is
      challenging, given the variation among patients and acute stroke care settings.
      Relatively few randomized trials have examined glycemic control protocols in this
      population, and there is not yet any clear evidence that "correcting"
      hyperglycemia in patients with acute stroke leads to better functional outcomes.
      Intensification of glucose regimens, using lower glucose targets, leads to more
      hypoglycemic events, but the immediate and long-term impact of these events on
      the acutely ischemic brain is unknown. It is reasonable to treat patients with
      acute ischemic stroke according to the American Diabetes Association inpatient
      glycemic control guidelines, initiating therapy to achieve glucose targets of 140
      to 180 mg/dL if fasting glucose is greater than 140 mg/dL or random glucose is
      consistently higher than 180 mg/dL. Lower glucose targets (<140 mg/dL) may be
      appropriate for patients with well-controlled diabetes and those with stress
      hyperglycemia who were not known to be diabetic before admission, but glucose
      levels less than 80 mg/dL should be avoided. Patients who present with extreme or
      persistent hyperglycemia, are critically ill, or who are treated with
      thrombolytic therapy should be started on an established and standardized
      intravenous insulin protocol to improve blood glucose control for at least the
      first 24 to 48 h of hospitalization. They should then be transitioned to a
      subcutaneous insulin regimen that includes basal long-acting insulin along with
      correction rapid-acting insulin for glucose that is out of range. Prandial (meal)
      insulin should be added for patients who are eating; this would preferably be a
      rapid-acting insulin analogue that can be administered immediately before or
      after the meal. Caution and close glucose monitoring are necessary, especially
      for patients prone to hypoglycemia, such as those with type 1 diabetes mellitus
      or hepatic or renal impairment, or those on complicated feeding regimens.

PMID- 21861125
TI  - Small-incision access retroperitoneoscopic technique (SMART) pyeloplasty in adult
      patients: comparison of cosmetic and post-operative pain outcomes in a matched
      pair analysis with standard retroperitoneoscopy: preliminary report.
AB  - OBJECTIVES: To present small-incision access retroperitoneoscopic technique
      pyeloplasty (SMARTp), a novel mini-laparoscopic approach for management of
      uretero-pelvic junction obstruction (UPJO) in adults including comparison with
      the standard retroperitoneoscopic technique (SRTp). METHODS: In a non-randomised
      study, we matched 12 adult patients treated from August to November 2010 by
      SMARTp with 12 patients treated with SRTp from January to November 2010. Mini
      laparoscopic retroperitoneal space was created with a home-made 6-mm balloon
      trocar. One 6-mm (for 5-mm 30 degrees  telescope) and two 3.5-mm trocars (for 3
      mm working instrument) were used. SRTp was performed with 11- and 6-mm trocar.
      Primary endpoints included evaluation of cosmetic appearance and post-operative
      pain evaluated respectively by the patient and observer scar assessment scale
      (POSAS) and analogue visual scale (VAS). Secondary endpoints were comparison
      between operative and functional parameters. RESULTS: Cosmetic cumulative results
      were statistically significant in favour of SMARTp (POSAS: 37.9 vs. 52.4; P =
      0.002). A better trend has been shown by post-operative pain (first to fourth day
      VAS), although not statistically significant (4.2 vs. 4.9, P = 0.891). No
      differences were recorded in terms of operative time, pre- and post-operative Hb
      difference, DJ-stent removal and resistive index (RI) improvement. The SMARTp
      group showed a faster drain removal (2.4 vs. 3.4 day, P = 0.004) and discharge
      (4.5 vs. 5.4 day P = 0.017). CONCLUSIONS: Preliminary data support SMARTp as safe
      procedures in experienced hands, providing better cosmetic results compared to
      SRTp. Further studies and clinical randomised trial performed in a larger
      population sample are requested.

PMID- 21861126
TI  - Novel strategies in imaging.

PMID- 21861128
TI  - The effect of thalidomide on the pharmacokinetics of irinotecan and metabolites
      in advanced solid tumor patients.
AB  - PURPOSE: Irinotecan and thalidomide are commonly administered antineoplastic
      drugs. Combination treatment may potentiate their antitumor effect and protect
      against irinotecan's intestinal toxicity. We investigated whether thalidomide can
      modulate the pharmacokinetics of irinotecan and metabolites. METHODS: The study
      employed a crossover design in which advanced solid tumor patients were
      randomized to two arms and treated with irinotecan 350 mg/m(2) intravenously (IV)
      every 3 weeks and thalidomide orally (p.o.) 400 mg daily. Pharmacokinetic data
      when irinotecan was administered as a single agent in each arm were compared to
      data when the two study agents were co-administered using paired t tests. Eighty
      percent and 90% confidence intervals for the true difference were also
      calculated. RESULTS: The differences in pharmacokinetic parameters and metabolic
      markers after thalidomide administration were small and unlikely to be clinically
      significant. With the exception of APC T (1/2), none of the upper confidence
      limits exceeds a 50% increase. CONCLUSIONS: This study did not find any
      clinically meaningful effects of thalidomide on the pharmacokinetics of
      irinotecan or its metabolites.

PMID- 21861129
TI  - Probenecid is a chemosensitizer in cancer cell lines.
AB  - Resistance and toxicity are the major barriers to successful cancer
      chemotherapies. Developing molecules that reduce drug resistance and improve
      antineoplastic effects is of great interest for cancer research; ideally, these
      substances should not affect the pharmacodynamics of the chemotherapeutic agent
      while providing a synergistic antineoplastic effect. In this study, we tested in
      vitro co-administration of the antineoplastic agents cisplatin or paclitaxel with
      probenecid, an anion channel inhibitor, in a panel of cancer cell lines to
      determine the cytotoxicity and synergistic effects of these drug combinations. In
      addition, we measured the clonogenicity and apoptotic index in these cells. We
      observed a synergistic interaction between probenecid and the chemotherapeutic
      agents, and increasing doses of probenecid resulted in a significant decrease in
      the effective doses of the chemotherapeutic agents. For the antineoplastic agent
      and probenecid combinations, we found increased cell death, reduced colony
      formation, and a higher number of apoptotic cells, compared with treatment of
      cisplatin or paclitaxel alone. Further research is necessary to elucidate the
      molecular mechanisms by which the synergistic effect occurs. If these synergistic
      effects can be reproduced in vivo, the co-administration of probenecid with
      different chemotherapeutic agents may provide a valid treatment in patients with
      chemotherapy resistance.

PMID- 21861130
TI  - Heavy metal contamination in the water-level fluctuating zone of the Yangtze
      River within Wanzhou Section, China.
AB  - The distribution, potential ecological hazards, and homologous relativity of
      heavy metals in the water-level fluctuating zone (WLFZ) of the Yangtze River
      within the Wanzhou Section (YRWS) were investigated. The heavy metal content (Cd,
      Cu, Cr, and Ni) of the surface soil was analysed via atomic absorption
      spectroscopy. The potential ecological hazards of the heavy metals in the WLFZ
      soil of YRWS were also evaluated using the classical Lars Hakanson potential
      ecological risk index method, and the relevance of the heavy metals in the soil
      was investigated. The average Cd, Cr, Cu, and Ni concentrations were 2.14, 35.43,
      18.47, and 34.52 mg/kg, respectively. The Cd and Ni contents in the soil exceeded
      the reference values in China by about 28.6- and 1.1-fold, respectively.
      Correlation analysis shows a highly significant correlation between Cd and Cr,
      indicating that their sources were the same. The major pollutant was Cd, which
      reached a very strong ecological hazard level. The potential ecological risk
      individual coefficients of the four heavy metals were ranked as follows: Cd
      (802.61) > Cu (4.43) > Ni (4.15) > Cr (1.23). The risk levels in the different
      regions were ranked as follows: Zhuxi River > mainstream > Mixi valley. The
      potential ecological risk in the WLFZ within the Zhuxi River was the highest
      among the regions and poses a certain health risk.

PMID- 21861131
TI  - Sublethal effect of copper toxicity against histopathological changes in the
      spiny lobster, Panulirus homarus (Linnaeus, 1758).
AB  - The tissue damage induced by various organic pollutants in aquatic animals is
      well documented, but there is a dearth of information relating to the
      histological alterations induced by copper in the spiny lobster. In the present
      study, intermoult juveniles of the spiny lobster Panulirus homarus (average
      weight 150-200 g) were exposed to two sublethal concentrations of the copper
      (9.55 and 19.1 MUg/l) for a period of 28 days. The muscle, hepatopancreas,
      midgut, gills, thoracic ganglion and heart of the lobsters were then dissected
      out and processed for light microscopic studies. Exposure to copper was found to
      result in several alterations in the histoarchitecture of the muscle,
      hepatopancreas, midgut, gills, thoracic ganglion and heart of P. homarus. The
      alterations included disruption and congestion of muscle bundle in muscle tissue;
      blackened haemocytes; distended lumen and F cell; necrosis of the tubules of the
      hepatopancreas; disarrangement of circular muscle of the midgut; accumulation of
      haemocytes in the haemocoelic space; swelling and fusion of lamellae; abnormal
      gill tips; hyperplastic, necrotic, and blackened secondary gill lamellae of the
      gills; damaged neurosecretory cell and sensory and motor fibre; necrotic of the
      thoracic ganglion; dispersedly arranged muscle bands; clumped satellite cells and
      nucleus of the heart. The results obtained suggest that the muscle,
      hepatopancreas, midgut, gills, thoracic ganglion and heart of lobsters exposed to
      copper were structurally altered. Such alterations could affect vital
      physiological functions, such as absorption, storage and secretion of the
      hepatopancreas, digestion of gut and respiration, osmotic and ionic regulations
      of the gills, which in turn could ultimately affect the survival and growth of P.
      homarus. Thus, all possible remedial measures should be adopted to prevent the
      occurrence of copper contamination in the aquatic environment.

PMID- 21861132
TI  - Boron contents of some wild-growing mushrooms collected from the vicinity of
      boron mines in Balikesir, Turkey.
AB  - The aim of the study was to determine the boron contents of some wild-growing
      mushrooms collected from the vicinity of several boron mines located in
      Balikesir, Turkey and compare the boron contents of some mushroom and soil
      samples. The locations of the mushroom samples collected were within the distance
      of 0-100, 100-500, and 500-1,000 m to the mines. Soil samples were taken from
      beneath randomly selected fungal fruit bodies. A total of 40 mushroom samples
      were found in the study area and 37 different species were identified. Among the
      40 samples analyzed, the highest boron content was detected to be 273 mg kg(-1)
      in Suillus collinitus. Also, Tricholoma terreum (69.52 mg kg(-1)), Myxomphalia
      maura (36.52 mg kg(-1)), Otidea concinna (30.70 mg kg(-1)), Sepultaria arenosa
      (28.94 mg kg(-1)), Melanoleuca paedida (28.33 mg kg(-1)), and Lycoperdon lividum
      (28.31 mg kg(-1)) relatively have high levels of boron and these species are
      proposed as candidates for boron accumulation. The boron contents of the other
      mushrooms varied and a pattern was observed where the boron content was found to
      be decreased as the distance from the mines increased.

PMID- 21861133
TI  - The role of caveolin-1 in blood-brain barrier disruption induced by focused
      ultrasound combined with microbubbles.
AB  - This research was designed to determine whether disrupting the blood-brain
      barrier (BBB) in rats by applying focused ultrasound (FUS) combined with
      microbubbles induced changes in the density of caveolae and/or the expression of
      the structural protein caveolin-1. To this end, two approaches were utilized.
      First, using enhanced magnetic resonance imaging, characteristics of BBB
      disruption induced by our specific FUS parameters and dose of microbubble were
      recorded, and the time after treatment when the BBB was the most permeable was
      determined. Second, rats were treated with FUS or microbubbles alone, both or
      neither, and a combination of Evans blue (EB) BBB permeability assays,
      streptavidin-peroxidase (SP) immunohistochemistry, western blot, and transmission
      electron microscopy (TEM) was employed to detect any changes in caveolae density
      and caveolin-1 expression at the previously determined time point when the BBB
      was the most permeable. The first set of studies revealed that our specific FUS
      parameters and dose of microbubbles were able to induce a transient, targeted,
      and reversible BBB opening in rats, and that the BBB was the most permeable 1 h
      after treatment with FUS and microbubbles. In the second set of experiments, the
      results of the SP immunohistochemistry, western blot, and TEM, taken together,
      revealed that caveolae and caveolin-1 were primarily localized in the brain
      microvascular endothelial cells of all of the rats regardless of treatment, and
      that caveolin-1 expression was highest in the rats treated with both FUS and
      microbubbles. In summary, treatment with FUS, in combination with a dose of
      microbubbles, can enhance BBB permeability through a caveolae-mediated
      transcellular approach by upregulating the expression level of caveolin-1 and,
      consequently, the amount of caveolae. This caveolin-1-mediated transcellular
      transport pathway may cooperate with other transport pathways to induce opening
      of the BBB. This research sheds light on the mechanism of a transient, targeted,
      and reversible opening of the BBB induced by FUS combined with microbubbles.

PMID- 21861134
TI  - Down-regulation of JAK1 by RNA interference inhibits growth of the lung cancer
      cell line A549 and interferes with the PI3K/mTOR pathway.
AB  - PURPOSE: The mammalian Janus kinase (JAK) family plays a critical role in
      cytokine/growth factor signalling pathways and is associated with human cancers.
      In this study, we explored the role of JAK1 in the non-small cell lung cancer
      (NSCLC) cell line A549 and its molecular crosstalk with the phosphatidyl inositol
      3-kinase (PI3K)/mammalian target of the rapamycin (mTOR) pathway. METHODS: One
      hundred and two NSCLC and 50 normal lung specimens were collected after surgical
      resection. JAK1 expression and phosphorylation were determined via
      immunohistochemical staining (IHC) assay. A stable knockdown of JAK1 was
      performed in A549 cells by RNA interference. Stable cell proliferation, cell
      cycle, apoptosis, and invasion were characterised in vitro. Tumourigenicity was
      analysed in vivo. The NSCLC xenograft protein expression of PI3K/mTOR pathway
      molecules was determined by Western blot assay. RESULTS: JAK1 expression was
      higher in NSCLC tissues than in normal lung tissues (P < 0.01). JAK1 knockdown in
      A549 cells significantly inhibited cell proliferation and invasion while
      promoting cell arrest at G0/G1 phase (all P < 0.05). The xenograft model showed
      that JAK1 suppression inhibited tumour growth compared with normal control (P <
      0.05). Moreover, JAK1 knockdown inhibited mTOR or P70 ribosomal protein S6 kinase
      (P70S6K) phosphorylation, but increased glycogen synthase kinase-3alpha (GSK
      3alpha) and B-cell lymphoma-extra large (Bcl-xl) phosphorylation. Total protein
      expression and Akt1/2 phosphorylated status remained unchanged. CONCLUSION: Our
      study suggests that JAK1 expression and phosphorylation is abnormal in NSCLC
      tissues. The knockdown of JAK1 significantly inhibits tumourigenicity of the A549
      cell line and demonstrates that crosstalk between the JAK1 and PI3K/mTOR pathways
      is involved.

PMID- 21861136
TI  - Reflection on studies on the learning process in problem-based learning.

PMID- 21861135
TI  - BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of
      malignant pleural mesothelioma patients.
AB  - PURPOSE: Malignant pleural mesothelioma is an incurable, asbestos-associated
      cancer. Its incidence is rapidly increasing and survival remains short. Apoptosis
      deregulation is an important feature of cancer and survivin, a member of the
      inhibitor-of-apoptosis-protein family encoded by the BIRC5 gene, has been
      suggested to have a role in the development and progression of several cancers.
      Genetic variability, in particular single nucleotide polymorphisms in the BIRC5
      promoter, may affect the protein's expression levels. The aim of our study was to
      elucidate the effects of BIRC5 promoter single nucleotide polymorphisms on
      survivin expression, patient survival and age at diagnosis in malignant pleural
      mesothelioma. METHODS: Archival mesothelioma samples from 101 Slovenian patients
      were immunohistochemically analysed for survivin expression. DNA was extracted
      from tumour samples and genotyped for three BIRC5 promoter single nucleotide
      polymorphisms (-31G > C, -241C > T and -625G > C). Genotypes were associated with
      nuclear survivin expression. Nuclear survivin expression, genotypes, haplotypes,
      histological type, gender and asbestos exposure were included in univariate Cox
      survival analyses. RESULTS: Survivin expression was detected in both tumour cell
      nuclei and cytoplasms in all analysed samples. No association between BIRC5
      promoter polymorphism genotypes or haplotypes and nuclear survivin expression was
      found. Polymorphism -241C > T affected patients' age at diagnosis. Survival
      analysis confirmed that younger age at diagnosis and epitheloid histological type
      improved survival, but no significant effects of nuclear survivin expression or
      genotype/haplotype on overall survival were observed. CONCLUSION: Our findings
      indicate no relationship between BIRC5 genotypes and survivin expression or
      overall survival in mesothelioma patients. We observed that BIRC5 -241C > T
      polymorphism had a significant effect on patient age at diagnosis.

PMID- 21861138
TI  - Head and neck manifestations of 22q11.2 deletion syndromes.
AB  - The allelic loss of 22q11.2 results in various developmental failures of
      pharyngeal pouch derivatives ("22q11.2 deletion syndromes", 22q.11DS),
      consequently affecting the anatomy and physiology of head and neck (H&N) organs.
      The objective of this paper was to describe those manifestations. Two 22q11.2DS
      patients with H&N manifestations were studied along with a comprehensive review
      of the English literature, from 1975 to 2010 regarding the associated H&N
      malformations among 22q11.2DS. A 24-year-old mentally disabled 22q11.2DS male
      presented with right hemithyroid enlargement, causing significant compressive
      signs. Sonography revealed a homogeneous 8 * 3 cm lesion, replacing almost the
      entire thyroid lobe. Fine needle aspiration revealed colloid material and
      abundant eosinophils. The hemithyroidectomy specimen confirmed follicular
      adenoma. A 19-year-old mentally disabled 22q11.2DS female underwent CT
      angiography due to an upper GI bleeding. The study revealed a vascular
      malformation in the infratemporal fossa. Reviewing the reported data regarding
      22q11.2DS-associated H&N malformations revealed abnormalities and malfunctions of
      the thyroid gland, parathyroid glands, thymus agenesis, cleft palate, carotid
      artery aberrations, malformations of the larynx and trachea and esophageal
      dysmotility. 22q11.DS patients may present with H&N anatomical abnormalities,
      along with hormonal dysfunctions, which require special awareness once treatment
      is offered, especially when concerning anesthetic and surgical aspects. In
      addition, hSNF5/INI1, a tumor suppressor gene, detected at location 22q11.2 was
      described to be "knocked out" in some patients. This may be associated with H&N
      tumors reported in these patients.

PMID- 21861139
TI  - Friedrich Hugo Kufs (1871-1955).

PMID- 21861137
TI  - Lipoic acid attenuates innate immune infiltration and activation in the visceral
      adipose tissue of obese insulin resistant mice.
AB  - Visceral adipose inflammation mediated by innate and adaptive immune alterations
      plays a critical role in diet-induced obesity and insulin resistance (IR). The
      dietary supplement alpha-lipoic acid (alphaLA) has been shown to ameliorate
      inflammatory processes in macrophages, however the relative significance of these
      effects in the context of visceral adipose inflammation and IR remain unknown. In
      this study we investigated its effects via both intraperitoneal and oral
      administration in lean and obese transgenic mice expressing yellow fluorescent
      protein (YFP) under control of a monocyte specific promoter (c-fms(YFP+)).
      alphaLA significantly improved indices of insulin-resistance concomitant with a
      decrease in total (YFP(+)CD11b(+)) and activated (YFP(+)CD11b(+)CD11c(+))
      visceral adipose tissue macrophages. Histologically, the visceral adipose tissue
      of obese mice receiving alphaLA had fewer "crown-like structures," a hallmark of
      adipose inflammation in murine obesity. Monocyte adhesion assessed by intravital
      microscopy of cremasteric venules was attenuated by alphaLA. In cultured WT and
      toll-like receptor 4 (TLR4) null primary mouse macrophages, alphaLA significantly
      decreased basal CCR-2, MCP-1 and TNF-alpha expression levels. LPS treatment
      resulted in increased TNFalpha, MCP-1, and IL-6 expression while alphaLA
      partially abrogated the LPS effect on MCP-1 and TNFalpha; Interestingly, CCR-2
      was not coordinately regulated. AalphaLA prevented LPS-induced nuclear factor
      kappa B (NFkappaB) activation in the same cultured macrophages. These data
      suggest that alphaLA may modulate visceral adipose inflammation, a critical
      determinant of IR via TLR4 and NF-kappaB pathways.

PMID- 21861141
TI  - Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant
      patients with gastroesophageal reflux disease and the dose escalation challenge
      of PPIs-TORNADO study: a multicenter prospective study by the Acid-Related
      Symptom Research Group in Japan.
AB  - BACKGROUNDS: Some non-erosive reflux disease (NERD) and reflux esophagitis (RE)
      patients are unresponsive to a proton pump inhibitor (PPI) at standard dose. We
      investigated the predictive marker of the efficacy of PPI for GERD patients
      including NERD and RE treated with standard and increased doses of a PPI.
      METHODS: Patients with symptomatic gastroesophageal reflux disease (GERD) (NERD
      and RE) were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. The RPZ
      dosage was increased to 10 mg twice daily for an additional 2 weeks and again to
      20 mg twice daily for another 2 weeks if heartburn was not relieved. Baseline
      characteristics and efficacy of RPZ were assessed on the basis of a heartburn
      diary and frequency scale for symptoms of GERD (FSSG). RESULTS: Complete
      heartburn relief rates after 4 weeks were 42.5% (31/73) and 67.9% (19/28) in NERD
      and RE groups, respectively, which rose to 68.9 and 91.7% after dose escalation.
      Multivariate analysis revealed that parameters associated with resistance to RPZ
      10 mg once daily were female, non-smoking, frequent heartburn, low score for
      question 4 (Q4) of the FSSG (subconsciously rubbing the chest), and high scores
      for Q3 (heavy stomach after meal) and Q7 (unusual sensation in the throat).
      Frequent heartburn and a high score for Q7 were associated with resistance to RPZ
      20 mg twice daily. FSSG scores of patients resistant to RPZ were significantly
      higher in comparison with responders before and during treatment. CONCLUSIONS:
      FSSG could predict response to a PPI for symptomatic GERD. Increase of RPZ dose
      is useful for treatment of GERD refractory to the standard dose of RPZ.

PMID- 21861143
TI  - Drain management after pancreatic resection: state of the art.
AB  - BACKGROUND: Placement of intraperitoneal drain (ID) after abdominal surgery is a
      common practice. Postoperative pancreatic fistula (POPF), incidence of which
      ranges from 2% to more than 30%, represents the most common major complication
      after pancreatic resection. The goal of this paper is to review the state of the
      art in ID management after pancreatic resection. METHODS: Data from randomized
      controlled trials (RCT) are reported together with data from our institution in
      the period before and after the start of the two reported RCTs. RESULTS: One
      thousand five hundred eighty patients underwent surgical resection for pancreatic
      lesions at our institution from 1990 to 2010. The overall rate of POPF was 23%
      before and 19.5% after (p = 0.24) the performance of the RCTs. Both postoperative
      morbidity and average in-hospital stay were higher in the period before the RCTs
      (13.6 +/- 11.4 versus 13.4 +/- 10.3 days, respectively). CONCLUSIONS: POPF is a
      complex and multifactorial complication after pancreatic surgery. On the basis of
      the present results and review of the RCTs, the value of ID and its management
      after pancreatic surgery remain unclear.

PMID- 21861142
TI  - SOX9 is expressed in normal stomach, intestinal metaplasia, and gastric carcinoma
      in humans.
AB  - BACKGROUND: SOX9 is a marker for stem cells in the intestine and overexpression
      of SOX9 is found in some types of cancer. However, the expression of SOX9 in
      normal stomach, precancerous intestinal metaplasia, and gastric carcinoma has not
      yet been clarified. This study aimed to investigate SOX9 expression in the corpus
      and pyloric regions of the normal human stomach, premalignant intestinal
      metaplasia, and gastric carcinoma by using immunohistochemistry. METHODS: We
      evaluated SOX9 expression in 46 clinical samples (early gastric well
      differentiated adenocarcinoma including surrounding intestinal metaplasia)
      resected under esophagogastroduodenoscopy. RESULTS: A small amount of SOX9 was
      expressed in the neck/isthmus of the corpus region and SOX9 expression was
      predominantly restricted to the neck/isthmus of the pyloric region in normal
      human stomach. In the intestinal metaplastic mucosa, SOX9- and PCNA-positive
      cells were located at the base of the intestinal metaplastic mucosa. Almost all
      of the gastric carcinoma cells expressed SOX9. CONCLUSION: SOX9 is expressed in
      intestinal metaplasia and gastric carcinoma in humans.

PMID- 21861144
TI  - Pancreaticoduodenectomy versus pylorus-preserving pancreaticoduodenectomy: the
      clinical impact of a new surgical procedure; pylorus-resecting
      pancreaticoduodenectomy.
AB  - Pylorus-preserving pancreaticoduodenectomy (PpPD) has been performed increasingly
      for periampullary tumors as a modification of conventional
      pancreaticoduodenectomy (PD) with antrectomy. Five randomized controlled trials
      (RCTs) and two meta-analyses have been performed to compare PD with PpPD. The
      results of these trials have shown that the two procedures were equally effective
      concerning morbidity, mortality, quality of life (QOL), and survival, although
      the length of surgery and blood loss were significantly lower for PpPD than for
      PD in one RCT and in the two meta-analyses. Delayed gastric emptying (DGE) is the
      major postoperative complication after PpPD. One of the pathogeneses of DGE after
      PpPD is thought to be denervation or devascularization around the pyloric ring.
      Therefore, one RCT was performed to compare PpPD with pylorus-resecting
      pancreaticoduodenectomy (PrPD; a new PD surgical procedure that resects only the
      pyloric ring and preserves nearly all of the stomach), concerning the incidence
      of DGE. The results clarified that the incidence of DGE was 4.5% after PrPD and
      17.2% after PpPD, which was a significant difference. Several RCTs of surgical or
      postoperative management techniques have been performed to reduce the incidence
      of DGE. One RCT for surgical techniques clarified that the antecolic route for
      duodenojejunostomy significantly reduced the incidence of DGE compared with the
      retrocolic route. Two RCTs examining postoperative management showed that the
      administration of erythromycin after PpPD reduced the incidence of DGE. 

PMID- 21861145
TI  - Call for a sudden cardiac death registry: should reporting of sudden cardiac
      death be mandatory?
AB  - There is currently no central mandatory pediatric sudden cardiac arrest (SCA)
      registry in the United States. Perhaps the time is right to actively endorse and
      develop a pediatric SCD registry, in collaboration with other agencies, advocacy
      groups, and organizations. This registry, if well constructed, thorough, and
      validated, would serve not only important SCD epidemiologic purposes but also
      provide the seed bed for closer collaboration with medical examiners and coroners
      and enhance critical cascade testing for identification of genotypically and/or
      phenotypically affected family members.

PMID- 21861148
TI  - Photobacterium atrarenae sp. nov. a novel bacterium isolated from sea sand.
AB  - The gram-reaction-negative, motile, facultatively anaerobic, catalase-positive,
      oxidase-positive bacterial strain M3-4(T) was isolated from black sea sand and
      subjected to a taxonomic study. Cells of strain M3-4(T) have monotrichous
      flagella, grow optimally at 37 degrees C and at pH 7-8 in the presence of 1-4%
      (w/v) NaCl and hydrolyze casein, starch and L: -tyrosine. According to
      phylogenetic analyses using 16S rRNA gene sequences, strain M3-4(T) belongs to
      the genus Photobacterium and is most closely related to Photobacterium
      rosenbergii LMG 22223(T) (97.4%) and P. gaetbulicola KCTC 22804(T) (96.6%). The
      DNA-DNA relatedness value between M3-4(T) and P. rosenbergii LMG 22223(T) was
      21.5%. The DNA G+C mol% of strain M3-4(T) was 53.6. The major cellular fatty acid
      of strain M3-4(T) was a summed feature 3 consisting of C(16:1) omega7c and/or iso
      C(15:0) 2-OH (35.0%), followed by C(16:0) (25.4%) and C(18:1)omega7c (16.8%).
      These data suggest that strain M3-4(T) represents a novel species in genus
      Photobacterium, for which the name P. atrarenae sp. nov. is proposed. The type
      strain is M3-4(T) (= KCTC 23265(T) = NCAIM B 02414(T)).

PMID- 21861146
TI  - Antenatal calcium channel blocker exposure and subsequent patent ductus
      arteriosus in extremely low-birth-weight infants.
AB  - This study aimed to assess whether tocolytic fetal exposure to antenatal calcium
      channel blockers (aCCB) increases the risk for hemodynamically significant patent
      ductus arteriosus (hsPDA) in extremely low-birth-weight (ELBW) infants. This case
      control study investigated ELBW infants (<1,000 g) without cardiac defects in a
      level 3 neonatal intensive care unit who had survived at least 7 days. Nifedipine
      was the only aCCB used for this study population. The measurements included the
      history of aCCB exposure, selected maternal data, hsPDA diagnosis, gestational
      age at birth, birth weight, mode of delivery, sex, maternal race, location of
      birth, Apgar scores, and selected neonatal morbidities. The end point of the
      study was hsPDA, defined as an echocardiographically confirmed PDA with clinical
      symptoms. A total of 180 infants met the study criteria. The diagnosis was hsPDA
      for 56% of these patients, 20% of whom had aCCB exposure. Of the infants without
      hsPDA, 11% had aCCB exposure (p = 0.09). No statistically significant
      associations were found between aCCB exposure and hsPDA after adjustment for
      gestational age (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.6-3.7) or
      for gestational age and cumulative aCCB exposure of 100 mg or more (OR, 2.0; 95%
      CI, 0.6-6.5). A history of aCCB exposure does not appear to increase hsPDA risk
      in ELBW infants. Studies using neonatal serum nifedipine concentrations after
      antenatal exposure should be performed to confirm this conclusion.

PMID- 21861149
TI  - Digestive enzymatic activity on tropical gar (Atractosteus tropicus) larvae fed
      different diets.
AB  - Digestive enzymatic activity and growth performance on tropical gar (Atractosteus
      tropicus) larvae fed Artemia nauplii (LF), frozen adult Artemia (AB), an
      artificial diet (AF) with 46% protein and 16% lipids and a starvation group (SG)
      from first feeding (5 days after hatching-5 DAH) to 34 DAH were studied. All
      larvae under starvation (SG) died at 15 DAH. By the end of the experimental
      period, morphological variables (total length, wet weight and specific growth
      rate) were significant in larvae fed AF compared to LF and AB. All enzymes
      studied in the experiment were present since the start of exogenous feeding
      (including pepsin) and the enzymatic activity varied with the diets. Low levels
      of enzymatic activity were observed until the 29 DAH; however, after this moment,
      there was a significant increase (eightfold), particularly for the AF treatment.
      In vitro protein digestibility tests performed with enzymatic extracts showed
      that artificial diets with 52% protein and 14% lipids were better digested by
      larvae before 30 DAH, while diets with 45% protein and 11% lipids were better
      digested after this age. Taking into account the better growth performance,
      higher enzymatic activity and better protein digestibility obtained, artificial
      diets can be used since the start of exogenous feeding on tropical gar larvae, as
      in other lepisosteids.

PMID- 21861150
TI  - [Translational research in head and neck cancer. Biological characteristics and
      general aspects].
AB  - Translational research in head and neck oncology is subject to the same laws as
      all other solid tumors. It is based on the one hand on a solid framework of well
      prepared clinical studies and / or workflows according to consensus criteria with
      comparable documentation of clinical outcomes, while on the other on
      methodolgically solid and reproducible laboratory research within an effeciently
      interacting network. Translationally applicable single molecular markers from
      basic research [with the exception of p16(INK4a) as a surrogate marker for human
      papillomavirus (HPV)] have not found their way into clinical routine in head and
      neck squamous cell carcinoma (HNSCC). "Correlated gene sets" and "metagenes",
      including genetic profiling (omics) within clinically characterized patient
      groups, play an increasing role in the translational research of HNSCC. Although
      methodological problems currently hinder clinical oncological research,
      increasing focus on translational research can be observed.

PMID- 21861151
TI  - Chronic hepatitis B infection in pregnancy illustrated by a case of successful
      treatment with entecavir.

PMID- 21861152
TI  - Development of a semi-high-throughput growth assay for the filamentous
      actinobacteria Frankia.
AB  - Filamentous bacteria pose unique challenges for testing multiple variables or
      growth parameters limiting the use of high-throughput methods. A semi-high
      throughput growth assay system was developed to overcome these obstacles and
      validated for the filamentous actinobacteria Frankia. The 24-well plate assay was
      versatile for testing multiple growth medium parameters and provided reproducible
      results across wells and between plates. Under conditions of increased
      complexity, statistical analysis demonstrated that the variance was dependent on
      the experimental parameters and not the assay system. The 24-well plate assay was
      shown to be multipurpose for testing numerous variables on cell growth or other
      biological properties.

PMID- 21861153
TI  - Identification and characterization of novel esterases from a deep-sea sediment
      metagenome.
AB  - A deep-sea sediment metagenomic library was constructed and screened for
      lipolytic enzymes by activity-based approach. Nine novel lipolytic enzymes were
      identified, and the amino acid sequences shared 56% to 84% identity to other
      lipolytic enzymes in the database. Phylogenetic analysis showed that these
      enzymes belonged to family IV lipolytic enzymes. One of the lipolytic enzymes,
      Est6, was successfully cloned and expressed in Escherichia coli Rosetta in a
      soluble form. The recombinant protein was purified by Ni-nitrilotriacetic
      affinity chromatography column and characterized using p-nitrophenyl esters with
      various chain lengths. The est6 gene consisted of 909 bp that encoded 302 amino
      acid residues. Est6 was most similar to a lipolytic enzyme from uncultured
      bacterium (ACL67845, 61% identity) isolated from the South China Sea marine
      sediment metagenome. The characterization of Est6 revealed that it was a cold
      active esterase and exhibited the highest activity toward p-nitrophenyl butyrate
      (C4) at 20 degrees C and pH 7.5.

PMID- 21861154
TI  - Substrate binding to mammalian 15-lipoxygenase.
AB  - Lipoxygenases (LOs) are implicated in the regulation of metabolic processes and
      in several human diseases. Revealing their exact role is hindered by an
      incomplete understanding of their activity, including substrate specificity and
      substrate alignment in the active site. Recently, it has been proposed that the
      change in substrate specificity for arachidonic acid (AA) or linoleic acid (LA)
      could be part of an auto-regulatory mechanism related to cancer grow. Kinetic
      differences between reactions of 15-hLO with AA and LA have also led to the
      suggestion that the two substrates could present mechanistic differences. In the
      absence of a crystal structure for the substrate:15-LO complex, here we present
      an atomic-level study of catalytically competent binding modes for LA to rabbit
      15-LO (15-rLO-1) and compare the results to our previous work on AA. Docking
      calculations, molecular dynamics simulations, re-docking and cross-docking
      calculations are all used to analyze the differences and similarities between the
      binding modes of the two substrates. Interestingly, LA seems to adapt more easily
      to the enzyme structure and differs from AA on some dynamical aspects that could
      introduce kinetic differences, as observed experimentally. Still, our study
      concludes that, despite the different chain lengths and number of insaturations
      between these two physiological substrates of 15-rLO-1, the enzyme seems to
      catalyze their hydroperoxidation by binding them with a common binding mode that
      leads to similar catalytically competent complexes.

PMID- 21861155
TI  - Ultrasonographic evaluation of geniohyoid muscle movement during swallowing: a
      study on healthy adults of various ages.
AB  - Our purpose in this study was to investigate the application of B+M-mode
      ultrasound (B/M-mode) imaging as a new approach to quantifying activity patterns
      of the geniohyoid muscles during swallowing and to assess how these patterns
      differ according to age and gender. Sixty healthy volunteers (30 men, 30 women)
      were divided into three age groups (20-39, 40-59, 60-79 years). The subjects were
      then given 10 ml of mineral water. Ultrasonographic imaging was repeated 5 times
      and measurements were averaged. Simultaneous B/M-mode images were captured at two
      regions along the lateral geniohyoid muscle wall. All geniohyoid muscle movement
      was recorded by real-time B/M-mode. In all cases, ultrasonographic images of the
      geniohyoid muscle movement during swallowing were easily visualized with the use
      of real-time B/M-mode. The average moving distance and the duration of movement
      of the geniohyoid muscle during contraction increased gradually with age. There
      was a significant difference in ultrasonic measurements of the moving distance
      and the duration of movement during swallowing between males and females in the
      three age groups (P < 0.05). B/M-mode imaging provides a simple, noninvasive
      technique for visual assessment of the lateral geniohyoid muscle wall and may
      provide a clinical method for evaluating swallowing.

PMID- 21861156
TI  - Structural noise from automatic exposure control device and its relationship to X
      ray tube voltage used for calibration of a flat-panel detector system.
AB  - In flat-panel detector (FPD) systems, the ion-chamber dosimeters used for
      automatic exposure control (AEC), which are placed between the detector and the
      source, should not affect clinical images because of FPD gain correction, but can
      sometimes still introduce fixed-pattern noise. In this study, we investigated
      whether such artifacts were caused by structural noise from the AEC detector on
      the basis of the noise power spectrum (NPS) and the mean square error (MSE) of
      FPD images taken at various tube voltages either with or without the AEC
      detector. When the NPS was measured without the AEC detector, the NPS did not
      increase in the low special-frequency band at all radiation qualities tested,
      irrespective of X-ray calibration tube voltages. However, when the NPS was
      measured while the AEC detector was used, the NPS increased in the low special
      frequency band at all radiation qualities when the X-ray calibration tube
      voltages were at low levels. Similarly, the MSE increased when the X-ray
      calibration tube voltages were at low levels. From these results, artifacts in
      the AEC detector appear to be suppressed when a radiation quality of
      approximately 90 kV is used at four different standardized radiations quality
      (RQA3, RQA5, RQA7, and RQA9).

PMID- 21861157
TI  - Computer aided three-dimensional reconstruction and modeling of the pelvis, by
      using plastinated cross sections, as a powerful tool for morphological
      investigations.
AB  - PURPOSE: The aim of this study was to describe a method of developing a
      computerized model of the human female pelvis using plastinated slices.
      Computerized reconstruction of anatomical structures is becoming very useful for
      developing anatomical teaching, research modules and animations. Although
      databases consisting of serial sections derived from frozen cadaver material
      exist, plastination represents an alternative method for developing anatomical
      data useful for computerized reconstruction. METHODS: A slice anatomy study,
      using plastinated transparent pelvis cross sections, was performed to obtain a 3D
      reconstruction. One female human pelvis used for this study, first plastinated as
      a block, then sliced into thin slices and in the end subjected to 3D computerized
      reconstruction using WinSURF modeling system (SURFdriver Software). To facilitate
      the understanding of the complex pelvic floor anatomy on sectional images
      obtained through MR imaging, and to make the representation more vivid, a female
      pelvis computer-aided 3D model was created. RESULTS: Qualitative observations
      revealed that the morphological features of the model were consistent with those
      displayed by typical cadaveric specimens. The quality of the reconstructed images
      appeared distinct, especially the spatial positions and complicated relationships
      of contiguous structures of the female pelvis. All reconstructed structures can
      be displayed in groups or as a whole and interactively rotated in 3D space.
      CONCLUSIONS: The utilization of plastinates for generating tissue sections is
      useful for 3D computerized modeling. The 3D model of the female pelvis presented
      in this paper provides a stereoscopic view to study the adjacent relationship and
      arrangement of respective pelvis sections. A better understanding of the pelvic
      floor anatomy is relevant to gynaecologists, radiologists, surgeons, urologists,
      physical therapists and all professionals who take care of women with pelvic
      floor dysfunction.

PMID- 21861158
TI  - Global transcriptome analysis of the tetrachloroethene-dechlorinating bacterium
      Desulfitobacterium hafniense Y51 in the presence of various electron donors and
      terminal electron acceptors.
AB  - Desulfitobacterium hafniense Y51 is a dechlorinating bacterium that encodes an
      unusually large set of O-demethylase paralogs and specialized respiratory systems
      including specialized electron donors and acceptors. To use this organism in
      bioremediation of tetrachloroethene (PCE) or trichloroethene (TCE) pollution,
      expression patterns of its 5,060 genes were determined under different conditions
      using 60-mer probes in DNA microarrays. PCE, TCE, fumarate, nitrate, and dimethyl
      sulfoxide (DMSO) respiration all sustain the growth of strain Y51. Global
      transcriptome analyses were thus performed using various electron donor and
      acceptor couples (respectively, pyruvate and either fumarate, TCE, nitrate, or
      DMSO, and vanillate/fumarate). When TCE is used as terminal electron acceptor,
      resulting in its detoxification, a series of electron carriers comprising a
      cytochrome bd-type quinol oxidase (DSY4055-4056), a ferredoxin (DSY1451), and
      four Fe-S proteins (DSY1626, DSY1629, DSY0733, DSY3309) are upregulated,
      suggesting that the products of these genes are involved in PCE oxidoreduction.
      Interestingly, the PCE dehalogenase cluster (pceABCT) is constitutively expressed
      in the media tested, with pceT being upregulated and pceC downregulated in
      pyruvate/TCE-containing medium. In addition, another dehalogenation enzyme
      (DSY1155 coding for a putative chlorophenol reductive dehalogenase), is induced
      225-fold in that medium, despite not being involved in PCE respiration.
      Remarkably since the reducing equivalents formed during pyruvate conversion to
      acetyl-CoA are channeled to electron acceptors including halogenated compounds,
      pyruvate induces expression of a pyruvate:ferredoxin oxidoreductase. This study
      paves the way to understanding the physiology of D. hafniense, optimizing this
      microbe as a bioremediation agent, and designing bioarray sensors to monitor the
      presence of dechlorinating organisms in the environment.

PMID- 21861159
TI  - Sensory deprivation differentially impacts the dendritic development of pyramidal
      versus non-pyramidal neurons in layer 6 of mouse barrel cortex.
AB  - Early postnatal sensory experience can have profound impacts on the structure and
      function of cortical circuits affecting behavior. Using the mouse whisker-to
      barrel system we chronically deprived animals of normal sensory experience by
      bilaterally trimming their whiskers every other day from birth for the first
      postnatal month. Brain tissue was then processed for Golgi staining and neurons
      in layer 6 of barrel cortex were reconstructed in three dimensions. Dendritic and
      somatic parameters were compared between sensory-deprived and normal sensory
      experience groups. Results demonstrated that layer 6 non-pyramidal neurons in the
      chronically deprived group showed an expansion of their dendritic arbors. The
      pyramidal cells responded to sensory deprivation with increased somatic size and
      basilar dendritic arborization but overall decreased apical dendritic parameters.
      In sum, sensory deprivation impacted on the neuronal architecture of pyramidal
      and non-pyramidal neurons in layer 6, which may provide a substrate for observed
      physiological and behavioral changes resulting from whisker trimming.

PMID- 21861161
TI  - [Misconduct in therapeutic relationships].

PMID- 21861160
TI  - The psychometric properties of the Peters et al. delusions inventory (PDI) in
      Taiwan: reliability, validity, and utility.
AB  - PURPOSE: The Peters et al. Delusions Inventory (PDI) is a commonly used
      instrument to measure delusion proneness in the general population and includes
      dimensions that measure distress, preoccupation, and conviction of unusual
      beliefs. This self-report scale has already been translated into several
      languages. However, there has not been a validated Taiwanese version previously
      reported. The aims of the present study were to translate and test the cross
      cultural reliability and validity of the PDI in Taiwanese as well as to establish
      its sensitivity, specificity, and discriminative validity. METHODS: We
      administered the questionnaire to a consecutive sample of 253 participants with
      (n = 154; clinical group including schizophrenia and affective psychosis) or
      without psychotic disorders (n = 99; non-clinical group). In addition to the
      Taiwanese version of the PDI (PDI-T), the Taiwanese version of the Brief
      Psychiatric Symptom Rating Scale (BSRS) was used to measure the severity of
      psychopathology. We tested the psychometric properties of the PDI-T, including
      its construct validity, internal consistency, test-retest reliability,
      concurrent, and discriminative validity. RESULTS: Overall, the PDI-T showed good
      construct validity, internal consistency, and stability over time, and it was
      significantly correlated with the BSRS subscales of psychotic symptoms. The
      convergent and discriminative validity was satisfactory. The area under the
      receiver operating characteristic curve of the PDI-T was 0.752. This research
      found that the most appropriate PDI-T yes/no cut-off scores for determining the
      absence and presence of delusion proneness were 5 and 13. CONCLUSIONS: The PDI is
      a reliable and valid instrument for measuring the dimensionality of delusion
      proneness and appears to complement subclinical psychosis assessment scales for
      both epidemiological and clinical research in Taiwan.

PMID- 21861162
TI  - Acute appendicitis complicated by septic mesenteric vein thrombophlebitis in an
      adult.

PMID- 21861164
TI  - From ancient to contemporary times: a concise history of incisional hernia
      repair.
AB  - PURPOSE: This historical review explores the origins of incisional hernia
      surgery. METHODS: Resources from each significant historical time period were
      reviewed, namely ancient times, the Greco-Roman period, the Middle Ages and the
      dawn of the surgeon anatomist, and the modern era. RESULTS: Although incisional
      hernias only started to be widely reported in the literature in the early
      twentieth century, an awareness of the risk of incisional hernia formation dates
      back to ancient times. CONCLUSIONS: Sometimes, it is important to look back at
      the history and evolution of a topic to continue making positive advances in that
      field.

PMID- 21861165
TI  - Mercury policy in the Great Lakes states: past successes and future
      opportunities.
AB  - While mercury (Hg) releases to air and water within the Great Lakes states have
      declined significantly, concentrations of mercury in fish remain a cause for
      concern regarding human and ecosystem health in the Great Lakes Basin. This paper
      assesses the priority that Hg source reduction ought to have in relation to some
      other environmental concerns, and explores the relative costs of various Hg
      reduction policies. Long-range transport of atmospheric mercury creates a
      collective action problem for states, since most of the mercury emitted within
      any given state deposits outside that state's borders, and since most of the
      mercury deposited within a state originated outside that state. This paper
      discusses some of the mechanisms that policy makers in the Great Lakes states
      employed to get beyond the collective action problem, including: providing an
      example for others to follow; using cross-jurisdiction cooperation to leverage
      the benefits of leadership on Hg reduction and control; and, promoting voluntary
      actions. Recommendations for future opportunities include: focusing reduction
      efforts on sources with the highest total mass of emissions rather than solely
      focusing on reduction of local deposition and utilizing all tools available in
      the clean air and clean water acts.

PMID- 21861166
TI  - Modelling the impact of toxic and disturbance stress on white-tailed eagle
      (Haliaeetus albicilla) populations.
AB  - Several studies have related breeding success and survival of sea eagles to toxic
      or non-toxic stress separately. In the present investigation, we analysed single
      and combined impacts of both toxic and disturbance stress on populations of white
      tailed eagle (Haliaeetus albicilla), using an analytical single-species model.
      Chemical and eco(toxico)logical data reported from laboratory and field studies
      were used to parameterise and validate the model. The model was applied to assess
      the impact of ?PCB, DDE and disturbance stress on the white-tailed eagle
      population in The Netherlands. Disturbance stress was incorporated through a 1.6%
      reduction in survival and a 10-50% reduction in reproduction. ?PCB contamination
      from 1950 up to 1987 was found to be too high to allow the return of white-tailed
      eagle as a breeding species in that period. ?PCB and population trends simulated
      for 2006-2050 suggest that future population growth is still reduced. Disturbance
      stress resulted in a reduced population development. The combination of both
      toxic and disturbance stress varied from a slower population development to a
      catastrophical reduction in population size, where the main cause was attributed
      to the reduction in reproduction of 50%. Application of the model was restricted
      by the current lack of quantitative dose-response relationships between non-toxic
      stress and survival and reproduction. Nevertheless, the model provides a first
      step towards integrating and quantifying the impacts of multiple stressors on
      white-tailed eagle populations.

PMID- 21861167
TI  - Profiling the aminopropyltransferases in plants: their structure, expression and
      manipulation.
AB  - Polyamines are organic polycations that are involved in a wide range of cellular
      activities related to growth, development, and stress response in plants. Higher
      polyamines spermidine and spermine are synthesized in plants and animals by a
      class of enzymes called aminopropyltransferases that transfer aminopropyl
      moieties (derived from decarboxylated S-adenosylmethionine) to putrescine and
      spermidine to produce spermidine and spermine, respectively. The higher
      polyamines show a much tighter homeostatic regulation of their metabolism than
      the diamine putrescine in most plants; therefore, the aminopropyltransferases are
      of high significance. We present here a comprehensive summary of the current
      literature on plant aminopropyltransferases including their distribution,
      biochemical properties, genomic organization, pattern of expression during
      development, and their responses to abiotic stresses, and manipulation of their
      cellular activity through chemical inhibitors, mutations, and genetic
      engineering. This minireview complements several recent reviews on the overall
      biosynthetic pathway of polyamines and their physiological roles in plants and
      animals. It is concluded that (1) plants often have two copies of the common
      aminopropyltransferase genes which exhibit redundancy of function, (2) their
      genomic organization is highly conserved, (3) direct enzyme activity data on
      biochemical properties of these enzymes are scant, (4) often there is a poor
      correlation among transcripts, enzyme activity and cellular contents of the
      respective polyamine, and (5) transgenic work mostly confirms the tight
      regulation of cellular contents of spermidine and spermine. An understanding of
      expression and regulation of aminopropyltransferases at the metabolic level will
      help us in effective use of genetic engineering approaches for the improvement in
      nutritional value and stress responses of plants.

PMID- 21861168
TI  - Effects of novel C-methylated spermidine analogs on cell growth via hypusination
      of eukaryotic translation initiation factor 5A.
AB  - The polyamines, putrescine, spermidine, and spermine, are ubiquitous
      multifunctional cations essential for cellular proliferation. One specific
      function of spermidine in cell growth is its role as a butylamine donor for
      hypusine synthesis in the eukaryotic initiation factor 5A (eIF5A). Here, we
      report the ability of novel mono-methylated spermidine analogs (alpha-MeSpd, beta
      MeSpd, gamma-MeSpd, and omega-MeSpd) to function in the hypusination of eIF5A and
      in supporting the growth of DFMO-treated DU145 cells. We also tested them as
      substrates and inhibitors for deoxyhypusine synthase (DHS) in vitro. Of these
      compounds, alpha-MeSpd, beta-MeSpd, and gamma-MeSpd (but not omega-MeSpd) were
      substrates for DHS in vitro, while they all inhibited the enzyme reaction. As
      racemic mixtures, only alpha-MeSpd and beta-MeSpd supported long-term growth (9
      18 days) of spermidine-depleted DU145 cells, whereas gamma-MeSpd and omega-MeSpd
      did not. The S-enantiomer of alpha-MeSpd, which supported long-term growth, was a
      good substrate for DHS in vitro, whereas the R-isomer was not. The long-term
      growth of DFMO-treated cells correlated with the hypusine modification of eIF5A
      by intracellular methylated spermidine analogs. These results underscore the
      critical requirement for hypusine modification in mammalian cell proliferation
      and provide new insights into the specificity of the deoxyhypusine synthase
      reaction.

PMID- 21861169
TI  - Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis
      in intestinal porcine epithelial cells.
AB  - alpha-Ketoglutarate (AKG) is a key intermediate in glutamine metabolism. Emerging
      evidence shows beneficial effects of AKG on clinical and experimental nutrition,
      particularly with respect to intestinal growth and integrity. However, the
      underlying mechanisms are unknown. Intestinal porcine epithelial cells (IPEC-1)
      were used to test the hypothesis that AKG inhibits glutamine degradation and
      enhances protein synthesis. IPEC-1 cells were cultured for 3 days in Dulbecco's
      modified Eagle's-F12 Ham medium (DMEM-F12) containing 0, 0.2, 0.5 or 2 mM of AKG.
      At the end of the 3-day culture, cells were used to determine L-[U-14C]glutamine
      utilization, protein concentration, protein synthesis, and the total and
      phosphorylated levels of the mammalian target of the rapamycin (mTOR), ribosomal
      protein S6 kinase-1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding
      protein-1 (4E-BP1). Compared with 0 mM of AKG (control), 0.2 and 0.5 mM of AKG
      dose-dependently reduced (P<0.05) glutamine degradation and the production of
      glutamate, alanine and aspartate in IPEC-1 cells. Addition of 0.5 and 2 mM of AKG
      to culture medium enhanced protein synthesis (P<0.05) by 78 and 101% without
      affecting protein degradation, compared to the control group. Rapamycin (50 nM; a
      potent inhibitor of mTOR) attenuated the stimulatory effect of AKG on protein
      synthesis. Consistent with these metabolic data, the addition of 0.5 or 2 mM of
      AKG to culture medium increased (P<0.05) the phosphorylated levels of mTOR, S6k1
      and 4E-BP1 proteins. Collectively, these results indicate that AKG can spare
      glutamine and activate the mTOR signaling pathway to stimulate protein synthesis
      in intestinal epithelial cells.

PMID- 21861170
TI  - Importance of amino acid composition to improve skin collagen protein synthesis
      rates in UV-irradiated mice.
AB  - Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are
      the major causes of skin photoaging. It has been shown that the one-time exposure
      of UV irradiation decreases procollagen mRNA expression in dermis and that
      chronic UV irradiation decreases collagen amounts and induces wrinkle formation.
      Amino acids are generally known to regulate protein metabolism. Therefore, we
      investigated the effects of UV irradiation and various orally administered amino
      acids on skin collagen synthesis rates. Groups of 4-5 male, 8-week-old HR-1
      hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then
      fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen
      was evaluated by incorporating L-[ring-2H5]-phenylalanine. We confirmed that the
      FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal
      tropocollagen was measured 30 min after a single oral administration of amino
      acids (1 g/kg) to groups of 5-16 UVB-irradiated mice. Branched-chain amino acids
      (BCAA, 1.34+/-0.32), arginine (Arg, 1.66+/-0.39), glutamine (Gln, 1.75+/-0.60),
      and proline (Pro, 1.48+/-0.26) did not increase the FSR of skin tropocollagen
      compared with distilled water, which was used as a control (1.56+/-0.30).
      However, essential amino acids mixtures (BCAA+Arg+Gln, BCAA+Gln, and BCAA+Pro)
      significantly increased the FSR (2.07+/-0.58, 2.04+/-0.54, 2.01+/-0.50 and 2.07+/
      0.59, respectively). This result suggests that combinations of BCAA and glutamine
      or proline are important for restoring dermal collagen protein synthesis impaired
      by UV irradiation.

PMID- 21861171
TI  - Increased in vivo release of neuropeptide S in the amygdala of freely moving rats
      after local depolarisation and emotional stress.
AB  - Intracerebral microdialysis in conjunction with a highly sensitive
      radioimmunoassay was used to study the in vivo release of neuropeptide S (NPS)
      within the amygdala of freely moving rats. NPS was consistently detected in
      basolateral amygdala dialysates and the release considerably enhanced in response
      to local depolarisation as well as exposure to forced swim stress. Thus, our data
      demonstrate for the first time emotional stress-induced release of NPS in the
      amygdala supporting a functional role of endogenous NPS in stress/anxiety-related
      phenomena.

PMID- 21861172
TI  - Contribution of insulin deficiency and insulin resistance to the development of
      type 2 diabetes: nature of early stage diabetes.
AB  - At the time of diagnosis of type 2 diabetes (T2D), patients already have varying
      degrees of beta-cell dysfunction and insulin resistance and the defects continue
      to deteriorate despite treatment. We examined insulin secretion impairment and
      insulin resistance in overweight patients with T2D who had metformin failure,
      with elevated HbA1c at maximal metformin dose. Patients (N = 1,039) were examined
      at entry to the European Exenatide (EUREXA) clinical trial of add-on exenatide
      versus sulphonylurea. Mean (+/-SD) age was 57 +/- 10 years, and BMI was 32.4 +/-
      4.1 kg/m(2). All patients underwent an oral glucose tolerance test; HOMA-IR, HOMA
      B, ?I(30)/?G(30), disposition index and pro-insulin/insulin ratio were evaluated
      in relation to stratified HbA1c levels (<=7.3, >7.3-8.2, >8.2%) and duration of
      diabetes (<3, >=3-<6, >=6 years) using non-parametric analysis of variance.
      Patients overall had a wide range of impaired insulin secretion (HOMA-B: median
      50.4, interquartile range 32.8-78.8) and insulin resistance (HOMA-IR: 4.8, 3.0
      7.4). With increasing HbA1c levels, there was a statistically significant
      decrease in HOMA-B (P < 0.001), ?I(30)/?G(30) (P = 0.003) and disposition index
      (P < 0.001), and increase in pro-insulin/insulin (P < 0.001) and HOMA-IR (P <
      0.001). With increasing duration since diabetes diagnosis, there was a
      significant decrease in HOMA-B (P < 0.001), but no significant trend in HOMA-IR,
      ?I(30)/?G(30), disposition index or pro-insulin/insulin. Metformin failure in
      these patients was associated with beta-cell dysfunction to a greater extent than
      insulin resistance. Loss of the first-phase insulin release, indicated by a low
      ?I(30)/?G(30), would indicate that this patient cohort requires add-on therapy
      that can maintain beta-cell function.

PMID- 21861174
TI  - Stable progeny production of the amphidiploid resynthesized Brassica napus cv.
      Hanakkori, a newly bred vegetable.
AB  - Resynthesized Brassica napus cv. Hanakkori (AACC, 2n = 38) was produced by cross
      hybridization between B. rapa (AA, 2n = 20) and B. oleracea (CC, 2n = 18) as a
      new vegetative crop. Many studies have provided evidences for the instability and
      close relationship between A and C genome in the resynthesized B. napus
      cultivars. In fact, seed produced to obtain progeny in Hanakkori had unstable
      morphological characters and generated many off-type plants. In this study, we
      investigated the pollen fertility, chromosome number, structure, and behavior
      linked to various Hanakkori phenotypes to define factors of unstable phenotypic
      expression in the progeny. Hanakkori phenotypes were categorized into five types.
      The results of pollen fertility, chromosome number, and fluorescence in situ
      hybridization analysis for somatic mitosis cells indicated that the off-type
      plants had lower pollen fertility, aberrant chromosome number, and structures
      with small chromosome fragments. Observation of chromosomes at meiosis showed
      that the meiotic division in off-type plants led to appreciably higher
      abnormalities than in on-type plants. However, polyvalent chromosomes were
      observed frequently in both on- and off-type plants in diplotene stage of
      meiosis. We assume that the unstable morphological characters in resynthesized
      progeny were the result of abnormal division in meiosis. It results as important
      that the plants of normal phenotype, chromosome structure and minimized abnormal
      meiosis are selected to stabilize progeny.

PMID- 21861175
TI  - [In vitro diagnosis and monitoring of Hymenoptera venom hyposensitization].
AB  - Specific immunotherapy (SIT) of hymenoptera venom allergy, in particular, has
      become an example for the effectiveness of the treatment of IgE-mediated allergic
      diseases. In vitro diagnostic procedures and the measurement of serum tryptase
      for risk assessment are well-established in the process of diagnose finding and
      therapy preparation. For monitoring and validation of the effectiveness of the
      SIT, however, in vitro diagnostic procedures remain controversial. Potentially
      useful approaches include detection of specific IgE, specific IgG4, basophile
      activation - represented by the CD 63 expression - and the lymphocyte
      proliferation and its IL10 release. Preliminary data suggest that the latter
      method appear appropriate, whereas the detection of basophile activation did not
      produce definite results.

PMID- 21861177
TI  - Do women exhibit greater differences in established and novel risk factors
      between diabetes and non-diabetes than men? The British Regional Heart Study and
      British Women's Heart Health Study.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is associated with greater relative risk of CHD
      in women than in men, which is not fully explained by conventional cardiovascular
      risk factors. We assessed whether cardiovascular risk factors including more
      novel factors such as markers of insulin resistance, inflammation, activated
      coagulation and endothelial dysfunction differ more between diabetic and non
      diabetic women than between diabetic and non-diabetic men, and the role of
      insulin resistance. METHODS: A cross-sectional study of non-diabetic and diabetic
      men and women (n = 7,529) aged 60-79 years with no previous myocardial infarction
      who underwent an examination was conducted. Measurements of anthropometry, blood
      pressure and fasting measurements of lipids, insulin, glucose and haemostatic and
      inflammatory markers were taken. RESULTS: Non-diabetic women tended to have more
      favourable risk factors and were less insulin resistant than non-diabetic men,
      but this was diminished in the diabetic state. Levels of waist circumference,
      BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR),
      diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA)
      and factor VIII differed more between diabetic and non-diabetic women than
      between diabetic and non-diabetic men (test for diabetes * sex interaction p <
      0.05). The more adverse effect of diabetes on these risk markers in women was
      associated with, and thereby largely attenuated by, insulin resistance.
      CONCLUSIONS/INTERPRETATION: The greater adverse influence of diabetes per se on
      adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial
      dysfunction and systemic inflammation in women compared with men may contribute
      to their greater relative risk of coronary heart disease.

PMID- 21861178
TI  - Methylglyoxal impairs insulin signalling and insulin action on glucose-induced
      insulin secretion in the pancreatic beta cell line INS-1E.
AB  - AIMS/HYPOTHESIS: Chronic hyperglycaemia aggravates insulin resistance, at least
      in part, by increasing the formation of advanced glycation end-products (AGEs).
      Methylglyoxal (MGO) is the most reactive AGE precursor and its abnormal
      accumulation participates in damage in various tissues and organs. Here we
      investigated the ability of MGO to interfere with insulin signalling and to
      affect beta cell functions in the INS-1E beta cell line. METHODS: INS-1E cells
      were incubated with MGO and then exposed to insulin or to glucose. Western
      blotting was used to study signalling pathways, and real-time PCR to analyse gene
      expression; insulin levels were determined by radioimmunoassay. RESULTS: Non
      cytotoxic MGO concentrations inhibited insulin-induced IRS tyrosine
      phosphorylation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)
      pathway activation independently from reactive oxygen species (ROS) production.
      Concomitantly, formation of AGE adducts on immunoprecipitated IRS was observed.
      Aminoguanidine reversed MGO inhibitory effects and the formation of AGE adducts
      on IRS. Further, the insulin- and glucose-induced expression of Ins1, Gck and
      Pdx1 mRNA was abolished by MGO. Finally, MGO blocked glucose-induced insulin
      secretion and PI3K/PKB pathway activation. These MGO effects were abolished by
      LiCl, which inhibits glycogen synthase kinase-3 (GSK-3).
      CONCLUSIONS/INTERPRETATION: MGO exerted major damaging effects on INS-1E cells
      impairing both insulin action and secretion. An important actor in these noxious
      MGO effects appears to be GSK-3. In conclusion, MGO participates not only in the
      pathogenesis of the debilitating complications of type 2 diabetes, but also in
      worsening of the diabetic state by favouring beta cell failure.

PMID- 21861180
TI  - The influence of natural variation at the foraging gene on thermotolerance in
      adult Drosophila in a narrow temperature range.
AB  - Poikilothermic organisms such as insects have mechanisms to protect neural
      function under high temperature stress. Natural variation at the foraging (for)
      locus of the fruit fly, Drosophila melanogaster, encoding a cGMP-dependent
      protein kinase (PKG), influences neural thermotolerance in Drosophila larvae. The
      current study re-examines thermotolerance of adult flies to account for
      inconsistencies in the documented role of for during hyperthermia. We found that
      adult for (R) (rover) flies with high PKG activity were incapacitated faster
      under hyperthermic conditions of 39 degrees C compared to their lower PKG
      activity counterparts for (s) and for (s2) (sitters), but not at higher
      temperatures. This indicates that lowered PKG activity promotes tolerance to heat
      stress, and that the for gene influences thermotolerance for a narrow range of
      temperatures in adult flies.

PMID- 21861179
TI  - The significance of expression of autophagy-related gene Beclin, Bcl-2, and Bax
      in breast cancer tissues.
AB  - The purpose of this study was to detect the expression of autophagy-related gene
      Beclin1 and apoptosis-related genes Bcl-2 and Bax in breast cancer tissues, to
      investigate their relationship and significance to the occurrence and development
      of breast cancer, and to provide an experimental basis for the biological
      treatment of breast cancer in the future. Human breast cancer tissues and
      relatively healthy breast tissue adjacent to the tumor were collected during
      surgical resection. By using RT-PCR and western blot, the mRNA and protein
      expressions of Beclin1, Bcl-2, and Bax were detected in the breast cancer tissues
      and the relatively healthy, adjacent tissues. The correlations of these
      expressions with the occurrence, development, and clinicopathology of breast
      cancer were analyzed. The mRNA and protein expressions of Beclin1 and Bcl-2 in
      breast cancer tissues were significantly lower than those in the relatively
      healthy, adjacent breast tissues (p < 0.05); the lower the degree of tumor
      differentiation, the lower the mRNA and protein expressions of Beclin1 and Bcl-2
      (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast
      cancer tissues from patients positive for lymph node metastasis were
      significantly lower than those negative for lymph node metastasis (p < 0.05); the
      mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from
      patients positive for distant metastasis were significantly lower than those
      negative for distant metastasis (p < 0.05); the mRNA and protein expressions of
      Beclin1 and Bcl-2 in breast cancer tissues from patients positive for ki67 were
      significantly lower than those negative for ki67 (p < 0.05). The mRNA and protein
      expressions of Bax were different from those of Beclin1 and Bcl-2. In breast
      cancer tissues, the mRNA and protein expressions of Bax were up-regulated (p <
      0.05); the lower the degree of tumor differentiation, the higher the mRNA and
      protein expressions of Bax (p < 0.05); the mRNA and protein expressions of Bax in
      breast cancer tissues from patients positive for lymph node metastasis were
      significantly higher than those negative for lymph node metastasis (p < 0.05);
      and the mRNA and protein expressions of Bax in breast cancer tissues from
      patients positive for distant metastasis were significantly higher than those in
      patients negative for distant metastasis (p < 0.05). However, the mRNA and
      protein expressions of these three genes were not correlated with patient age,
      tumor size, progesterone receptor positivity, or human epidermal growth factor
      positivity (p > 0.05). The correlation of Bcl-2 and Bax mRNA with Beclin1 mRNA
      expressed in breast cancer tissues were both statistically significant (p <
      0.05). The activity change of autophagy and apoptosis is associated with the
      tumorigenesis and tumor progression of breast cancer. The joint detection of
      these three genes (Beclin1, Bcl-2, and Bax) contributes to the early diagnosis of
      and predicts prognosis for breast cancer, and this also provides an experimental
      basis for the biological therapy of breast cancer.

PMID- 21861181
TI  - Food preferences and mound-building behaviour of the mound-building mice Mus
      spicilegus.
AB  - Optimal foraging strategies and food choice are influenced by various factors,
      e.g. availability, size and caloric content of the food type and predation risk.
      However, food choice criteria may change when food is not eaten immediately but
      has to be carried to a storage site for later use. For example, handling time in
      terms of harvesting and transport time should be optimized, particularly when the
      risk of predation is high. Thus, it is not clear whether food selected by
      hoarding animals reflects their food preference due to intrinsic features of the
      food type, e.g. size, caloric or lipid content, or whether the food type selected
      is a compromise that also considers the handling time required for harvesting and
      transport. We investigate this question in relation to food hoarding behaviour in
      mound-building mice. In autumn, mound-building mice Mus spicilegus collect seeds
      and other plant material and cover it with soil. Such above-ground storage is
      quite unusual for rodents. Here, we investigated whether there is a relationship
      between the seed species preferred as building materials and those preferred for
      food. We conducted a seed preference test using three most collected weed species
      for mound building. Controlling factors like food availability or predation risk,
      mice prefer Setaria spp. as food, although Amaranthus spp. and Chenopodium spp.
      were preferentially harvested and stored. By including the availability of the
      three species, our experimental results were confirmed, namely, a clear
      preference for Setaria spp. Also, handling time and seed size revealed to
      influence plant choice.

PMID- 21861182
TI  - Natural killer cell activation by dendritic cells: balancing inhibitory and
      activating signals.
AB  - Natural killer (NK) cells have originally been identified by their spontaneous
      cytolytic potential against tumor cells, which, however, might result from pre
      activation due to prior pathogen exposure. Resting NK cells, on the contrary,
      require activation by bystander antigen-presenting cells to reach their full
      functional competence. In this review, we will summarize studies on how dendritic
      cells (DCs), the most potent type of antigen-presenting cell, communicate with
      human NK cells to activate them in secondary lymphoid organs and to integrate
      signals from activated NK cells at sites of inflammation for their own
      maturation. Furthermore, we will review aspects of the immunological synapse,
      which mediates this cross-talk. These studies provide the mechanistic
      understanding of how mature DCs can activate NK cells and survive to go on for
      the activation of adaptive immunity. This feature of DCs, to activate different
      waves of immune responses, could be harnessed for immunotherapies, including
      vaccinations.

PMID- 21861183
TI  - Mechanisms of NK cell activation: CD4(+) T cells enter the scene.
AB  - Natural killer (NK) cells are innate lymphocytes involved in immunosurveillance
      through their cytotoxic activity and their capacity to secrete inflammatory
      cytokines. NK cell activation is necessary to initiate effector functions and
      results from a complex series of molecular and cellular events. We review here
      the signals that trigger NK cells and discuss recent findings showing that,
      besides antigen-presenting cells, T cells can play a central role in the
      initiation of NK cell activation in lymph nodes.

PMID- 21861184
TI  - Functions of the poly(ADP-ribose) polymerase superfamily in plants.
AB  - Poly(ADP-ribosyl)ation is the covalent attachment of ADP-ribose subunits from
      NAD(+) to target proteins and was first described in plants in the 1970s. This
      post-translational modification is mediated by poly(ADP-ribose) polymerases
      (PARPs) and removed by poly(ADP-ribose) glycohydrolases (PARGs). PARPs have
      important functions in many biological processes including DNA repair, epigenetic
      regulation and transcription. However, these roles are not always associated with
      enzymatic activity. The PARP superfamily has been well studied in animals, but
      remains under-investigated in plants. Although plants lack the variety of PARP
      superfamily members found in mammals, they do encode three different types of
      PARP superfamily proteins, including a group of PARP-like proteins, the SRO
      family, that are plant specific. In plants, members of the PARP family and/or
      poly(ADP-ribosyl)ation have been linked to DNA repair, mitosis, innate immunity
      and stress responses. In addition, members of the SRO family have been shown to
      be necessary for normal sporophytic development. In this review, we summarize the
      current state of plant research into poly(ADP-ribosyl)ation and the PARP
      superfamily in plants.

PMID- 21861186
TI  - Binding of ReO4(-) with an engineered MoO4(2-)-binding protein: towards a new
      approach in radiopharmaceutical applications.
AB  - Radiolabeled biomolecules are routinely used for clinical diagnostics. (99m)Tc is
      the most commonly used radioactive tracer in radiopharmaceuticals. (188)Re and
      (186)Re are also commonly used as radioactive tracers in medicine. However,
      currently available methods for radiolabeling are lengthy and involve several
      steps in bioconjugation processes. In this work we present a strategy to engineer
      proteins that may selectively recognize the perrhenate (ReO(4)(-)) ion as a new
      way to label proteins. We found that a molybdate (MoO(4)(2-))-binding protein
      (ModA) from Escherichia coli can bind perrhenate with high affinity. Using
      fluorescence and isothermal titration calorimetry measurements, we determined the
      dissociation constant of ModA for ReO(4)(-) to be 541 nM and we solved a crystal
      structure of ModA with a bound ReO(4)(-). On the basis of the structure we
      created a mutant protein containing a disulfide linkage, which exhibited
      increased affinity for perrhenate (K(d) = 104 nM). High-resolution crystal
      structures of ModA (1.7 A) and A11C/R153C mutant (2.0 A) were solved with bound
      perrhenate. Both structures show that a perrhenate ion occupies the molybdate
      binding site using the same amino acid residues that are involved in molybdate
      binding. The overall structure of the perrhenate-bound ModA is unchanged compared
      with that of the molybdate-bound form. In the mutant protein, the bound
      perrhenate is further stabilized by the engineered disulfide bond.

PMID- 21861185
TI  - Nod2: a key regulator linking microbiota to intestinal mucosal immunity.
AB  - The human intestine harbors a large number of bacteria that are constantly
      interacting with the intestinal immune system, eliciting non-pathological basal
      level immune responses. Increasing evidence points to dysbiosis of microbiota in
      the intestine as an underlying factor in inflammatory bowel disease
      susceptibility. Loss-of-function mutations in NOD2 are among the stronger genetic
      factors linked to ileal Crohn's disease. Indeed, Nod2 is a key regulator of
      microbiota in the intestine, as microflora in the terminal ileum is dysregulated
      in Nod2-deficient mice. Nod2 is highly expressed in Paneth cells, which are
      responsible for the regulation of ileal microflora by anti-microbial compounds,
      and Nod2-deficient ileal intestinal epithelia are unable to kill bacteria
      efficiently. It is therefore likely that NOD2 mutations in Crohn's disease may
      increase disease susceptibility by altering interactions between ileal microbiota
      and mucosal immunity.

PMID- 21861187
TI  - The effectiveness of postmortem multidetector computed tomography in the
      detection of fatal findings related to cause of non-traumatic death in the
      emergency department.
AB  - OBJECTIVES: To investigate the diagnostic performance of postmortem multidetector
      computed tomography (PMMDCT) for the detection of fatal findings related to
      causes of non-traumatic death in the emergency department (ED). METHODS: 494
      consecutive cases of clinically diagnosed non-traumatic death in ED involving
      PMMDCT were enrolled. The fatal findings were detected on PMMDCT and classified
      as definite or possible findings. These findings were confirmed by autopsy in 20
      cases. RESULTS: The fatal findings were detected in 188 subjects (38.1%)
      including 122 with definite (24.7%) and 66 with possible finding (13.4%).
      Definite findings included 21 cases of intracranial vascular lesions, 84 with
      intra-thoracic haemorrhage, 13 with retroperitoneal haemorrhage and one with
      oesophagogastric haemorrhage. In three patients who had initially been diagnosed
      with non-traumatic death, PMMDCT revealed fatal traumatic findings. Two definite
      findings (two haemopericardiums) and seven possible findings (two intestinal
      obstructions, one each of multiple liver tumours central pulmonary artery
      dilatation, pulmonary congestion, peritoneal haematoma, and brain oedema) were
      confirmed by autopsy. The causes of death were not determined in cases with
      possible findings without autopsy. CONCLUSIONS: PMMDCT is a feasible tool for
      detecting morphological fatal findings in non-traumatic death in ED. It is
      important to know the ability and limitation of PMMDCT.

PMID- 21861188
TI  - Hepatic and pancreatic involvement in hereditary hemorrhagic telangiectasia:
      quantitative and qualitative evaluation with 64-section CT in asymptomatic adult
      patients.
AB  - PURPOSE: To analyse quantitatively and qualitatively asymptomatic hepatic and
      pancreatic involvement in hereditary haemorrhagic telangiectasia (HHT) using 64
      section helical CT. MATERIALS AND METHODS: The 64-section helical CT examinations
      of 19 patients with HHT (8 men, 11 women; mean age, 58.6 years) were
      quantitatively and qualitatively analysed and compared to those of 19 control
      subjects who were matched for age and sex. Comparisons were made using univariate
      analysis. RESULTS: Dilated and tortuous intrahepatic arterial branches was the
      most discriminating independent variable (P < 0.0001) and had the highest
      specificity (100%; 19/19; 95%CI: 82%-100%) and accuracy (97%; 37/38; 95%CI: 86%
      100%) for the diagnosis of HHT. Heterogeneous enhancement of hepatic parenchyma,
      intrahepatic telangiectases, hepatic artery to hepatic vein shunting, hepatic
      artery enlargement (i.e. diameter > 6.5 mm) and portal vein enlargement (i.e.
      diameter > 13 mm) were other variables that strongly correlated with the presence
      of HHT. Intrapancreatic telangiectases and arteriovenous malformations were found
      in 42% and 16% of patients with HHT, respectively. CONCLUSION: Liver and
      pancreatic involvement in asymptomatic HHT patients is associated with myriad
      suggestive findings on 64-section helical CT. It can be anticipated that
      familiarity with these findings would result in more confident diagnosis of HHT.

PMID- 21861189
TI  - Reduction of metastasis using a non-volatile buffer.
AB  - The tumor microenvironment is acidic as a consequence of upregulated glycolysis
      and poor perfusion and this acidity, in turn, promotes invasion and metastasis.
      We have recently demonstrated that chronic consumption of sodium bicarbonate
      increased tumor pH and reduced spontaneous and experimental metastases. This
      occurred without affecting systemic pH, which was compensated. Additionally,
      these prior data did not rule out the possibility that bicarbonate was working
      though effects on carbonic anhydrase, and not as a buffer per se. Here, we
      present evidence that chronic ingestion of a non-volatile buffer, 2-imidazole-1
      yl-3-ethoxycarbonylpropionic acid (IEPA) with a pK (a) of 6.9 also reduced
      metastasis in an experimental PC3M prostate cancer mouse model. Animals (n = 30)
      were injected with luciferase expressing PC3M prostate cancer cells either
      subcutaneously (s.c., n = 10) or intravenously (i.v., n = 20). Four days prior to
      inoculations, half of the animals for each experiment were provided drinking
      water containing 200 mM IEPA buffer. Animals were imaged weekly to follow
      metastasis, and these data showed that animals treated with IEPA had
      significantly fewer experimental lung metastasis compared to control groups (P <
      0.04). Consistent with prior work, the pH of treated tumors was elevated compared
      to controls. IEPA is observable by in vivo magnetic resonance spectroscopy and
      this was used to measure the presence of IEPA in the bladder, confirming that it
      was orally available. The results of this study indicate that metastasis can be
      reduced by non-volatile buffers as well as bicarbonate and thus the effect
      appears to be due to pH buffering per se.

PMID- 21861191
TI  - The effects of electrical hippocampal kindling of seizures on amino acids and
      kynurenic acid concentrations in brain structures.
AB  - Our study demonstrated that the development of seizures during the electrically
      induced kindling of seizures is associated with significant changes in the
      concentration of kynurenic acid (KYNA) and its precursor, tryptophan (TRP). The
      primary finding of our study was an increase in KYNA levels and the KYNA/TRP
      ratio (a theoretical index of activity of the kynurenine pathway) in the amygdala
      and hippocampus of kindled animals. We also found decreases in the concentration
      of tryptophan in the hippocampus and prefrontal cortex. Changes in the
      concentration of KYNA and TRP in the amygdala were accompanied by a significant
      decrease in gamma-Aminobutryic Acid (GABA) levels and an increase in the
      glutamate/GABA ratio. Moreover, we found a significant negative correlation
      between the local concentrations of KYNA and glutamate in the amygdala of kindled
      rats. However, there were no changes in the local concentrations of the following
      amino acids: glutamate, aspartate, glutamine, glycine, taurine and alanine. In
      conclusion, these new results suggest a modulatory influence of KYNA on the
      process of epileptogenesis, characterized by a negative relationship between the
      KYNA and glutamate systems in the amygdala.

PMID- 21861192
TI  - Terfenadine induces apoptosis and autophagy in melanoma cells through ROS
      dependent and -independent mechanisms.
AB  - Previously we found that terfenadine, an H1 histamine receptor antagonist, acts
      as a potent apoptosis inducer in melanoma cells through modulation of Ca(2+)
      homeostasis. In this report, focusing our attention on the apoptotic mechanisms
      activated by terfenadine, we show that this drug can potentially activate
      distinct intrinsic signaling pathways depending on culture conditions. Serum
      deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and
      -2 are activated upstream of caspase-9. Moreover, although we found an increase
      in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine
      treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and 
      9 were simultaneously activated and p73 and Noxa induction were involved. ROS
      inhibition prevented p73 and Noxa expression but not p53 and p21 expression,
      suggesting a role for Noxa in p53-independent apoptosis in melanoma cells.
      Finally, we found that terfenadine induced autophagy, that can promote apoptosis.
      These findings demonstrate the great potential of terfenadine to kill melanoma
      cells through different cellular signaling pathways and could contribute to
      define new therapeutic strategies in melanoma.

PMID- 21861194
TI  - Size, composition, and strength of ties of personal social support networks among
      adult people living with HIV/AIDS in Henan and Beijing, China.
AB  - To characterize the level of personal support available to people living with
      HIV/AIDS (PLWHA) in Henan and Beijing, China, face-to-face interviews were
      conducted to collect information on network size, composition, and strength of
      ties. The number of people as sources of support for participants in Henan varied
      from 1 to 13 and 1 to 16 in Beijing. In Henan, family members were more likely to
      provide support than non-relatives and they provided support more frequently; in
      Beijing non-relatives were more likely to provide support than family members.
      Family members were closer to PLWHA than non-relatives in both sites, but the
      closest type of relative and non-relative supporters were different between Henan
      and Beijing. PLWHA in Henan and Beijing receive considerable social support, but
      there is still opportunity for additional social support. Efforts should be made
      to mobilize civil society to provide support for PLWHA in China.

PMID- 21861193
TI  - Social and sexual network characteristics and concurrent sexual partnerships
      among urban African American high-risk women with main sex partners.
AB  - Social networks, including sexual networks, have increasingly been considered in
      research addressing HIV disparities in the United States. The goal of this study
      is to examine correlates of concurrent involvement in multiple sexual
      partnerships with social (i.e., non-sexual) and sexual network characteristics
      among a sample of 337 low-income urban African American women reporting main
      sexual partnerships longer than 6 months in duration. In the multivariate
      analyses, women who had larger non-sexual social networks, more family members in
      that network, and reported high levels of trust in their partner(s) were less
      likely to be in concurrent partnerships. Women who had one or more sexual partner
      who used drugs in the past 6 months were more likely to be in concurrent
      partnerships. Our results provide further evidence of the important association
      of drug use and concurrent sexual partnerships, but suggest that family members,
      immediate and extended, may be an important area of focus in addition to
      structural interventions that address the root causes of poverty and drug abuse.

PMID- 21861195
TI  - Noninvasive intracranial pressure measurement using infrasonic emissions from the
      tympanic membrane.
AB  - OBJECTIVE: We investigated whether ICP can be assessed by measuring infrasonic
      emissions from the tympanic membrane. METHODS: An increase in ICP was induced in
      22 patients with implanted ICP pressure sensors. ICP waveforms that were obtained
      invasively and continuously were compared with infrasonic emission waveforms. In
      addition, the noninvasive method was used in a control group of 14 healthy
      subjects. RESULTS: In a total of 83 measurements, the changes in ICP that were
      observed in response to different types of stimulation were detected in the
      waveforms obtained noninvasively as well as in those acquired invasively. Low ICP
      was associated with an initial high peak and further peaks with smaller
      amplitudes. High ICP was associated with a marked decrease in the number of peaks
      and in the difference between the amplitudes of the initial and last peaks. The
      assessment of infrasonic emissions, however, does not yet enable us to provide
      exact figures. CONCLUSION: It is conceivable that the assessment of infrasonic
      emissions will become suitable both as a screening tool and for the continuous
      monitoring of ICP in an intensive care environment.

PMID- 21861196
TI  - Single and hypofractionated stereotactic radiotherapy with CyberKnife for
      craniopharyngioma.
AB  - Craniopharyngiomas are slow-growing tumors found in the suprasellar region, with
      especially high incidence in Japanese children. Due to the location, proximity
      and adhesiveness of the tumor to adjacent critical structures, these tumors
      remain a significant clinical challenge. The purpose of this study was to
      evaluate the clinical outcome of single and hypofractionated stereotactic
      radiotherapy (SRT) with CyberKnife for craniopharyngioma. Forty-three patients
      (21 men and 22 women; median age 44 years; range 3-85 years) were treated at two
      institutions. Three cases were treated in a single fraction to a marginal dose of
      13-16 Gy. The other 40 cases were treated in 2-5 fractions to a marginal dose of
      13-25 Gy. Tumor volumes ranged from 0.09 to 20.8 cm(3) (median 2.0 cm(3)).
      Toxicities were evaluated with the Common Terminology Criteria for Adverse Events
      version 4.0. The median follow-up period was 40 months (range 12-92 months). The
      3-year overall survival and local control rates were 100 and 85%, respectively.
      In-field cyst enlargement was observed in 9 patients. These tumors had
      significantly larger volumes (mean 6.9 cm(3); 95% confidence interval, CI, 2.8
      10.9 cm(3)) than the 34 controlled tumors (2.9 cm(3); CI 1.5-4.3 cm(3)) (P =
      0.02). Out-field tumor regrowth was observed in 4 patients. No radiation-induced
      symptomatic visual disorder or brain necrosis was observed. Hypopituitarism was
      observed in only 1 patient. Single and hypofractionated SRT using CyberKnife
      produced high tumor control rates with minimal complications. Hypofractionated
      SRT may be useful for protecting the visual nerve and neuroendocrine function,
      especially for tumors located near the optic pathways and for large tumors.

PMID- 21861197
TI  - HESRG: a novel biomarker for intracranial germinoma and embryonal carcinoma.
AB  - The novel stem cell-related gene, HESRG, was first identified by our group, and
      its expression pattern in human tumors remains unknown. In this study, we used RT
      PCR to systematically investigate the expression of HESRG in various types of
      intracranial tumors and found that HESRG was expressed only in germinoma and
      embryonal carcinoma, but hardly at all  in other types of brain tumors. Real-time
      PCR results further confirmed this expression pattern. Subsequently, we tested
      134 intracranial non-germ cell tumors and 64 intracranial germ cell tumors by
      immunohistochemistry. Our results showed that HESRG was expressed strongly and
      diffusively in the nuclei of tumor cells in intracranial germinoma and embryonal
      carcinoma as well as in human embryonic stem cells. No positive staining signal
      was observed in any other type of intracranial tumors. In germinomas, 25 of 31
      showed intensive (3+) expression, four cases showed moderate (2+) immunostaining
      and the remaining 2 cases showed weak (1+) immunostaining. In embryonal
      carcinoma, 6 of 9 showed intensive (3+) immunostaining and 3 of 9 showed moderate
      (2+) immunostaining. These results suggest that HESRG is a novel, sensitive and
      specific biomarker for intracranial germinoma and embryonal carcinoma.

PMID- 21861198
TI  - "I felt like the angel of death": role conflicts and moral distress among allied
      professionals employed by the US cardiovascular implantable electronic device
      industry.
AB  - PURPOSE: This study aimed to identify themes associated with role conflicts and
      moral distress experienced by cardiovascular implantable electronic device (CIED)
      industry-employed allied professionals (IEAPs) in the clinical setting. METHODS:
      Focus groups were used to elicit perspectives from IEAPs who had deactivated a
      CIED. RESULTS: Seventeen IEAPs (five women) reported increased clinical presence
      and work-related role conflicts and moral distress along several themes: (1)
      relationships with patients, (2) relationships with clinicians, (3) role
      ambiguity, (4) customer service to clinicians, and (5) CIED deactivation.
      Patients often misperceived IEAPs as physicians or nurses. Many physicians
      expected IEAPs to perform clinical duties. Customer service obligations
      exacerbated IEAP role conflicts and moral distress because of dual agency. IEAPs
      commonly received and carried out requests to deactivate CIEDs; doing so,
      however, generated considerable distress-particularly deactivations of pacemakers
      in pacemaker-dependent patients. Several described themselves as "angels of
      death." IEAPs had recommendations for mitigating role conflicts and moral
      distress, including improving the deactivation process. CONCLUSIONS: IEAPs
      experienced role conflicts and moral distress regarding their activities in the
      clinical setting and customer service obligations. Health care institutions
      should develop and enforce clear boundaries between IEAPs and clinicians in the
      clinical setting. Clinicians and IEAPs should adhere to these boundaries.

PMID- 21861199
TI  - Optimal experimental design for sampling voltage on dendritic trees in the low
      SNR regime.
AB  - Due to the limitations of current voltage sensing techniques, optimal filtering
      of noisy, undersampled voltage signals on dendritic trees is a key problem in
      computational cellular neuroscience. These limitations lead to voltage data that
      is incomplete (in the sense of only capturing a small portion of the full
      spatiotemporal signal) and often highly noisy. In this paper we use a Kalman
      filtering framework to develop optimal experimental design methods for voltage
      sampling. Our approach is to use a simple greedy algorithm with lazy evaluation
      to minimize the expected square error of the estimated spatiotemporal voltage
      signal. We take advantage of some particular features of the dendritic filtering
      problem to efficiently calculate the Kalman estimator's covariance. We test our
      framework with simulations of real dendritic branching structures and compare the
      quality of both time-invariant and time-varying sampling schemes. While the
      benefit of using the experimental design methods was modest in the time-invariant
      case, improvements of 25-100% over more naive methods were found when the
      observation locations were allowed to change with time. We also present a
      heuristic approximation to the greedy algorithm that is an order of magnitude
      faster while still providing comparable results.

PMID- 21861200
TI  - Efficacy of opioid rotation to continuous parenteral hydromorphone in advanced
      cancer patients failing on other opioids.
AB  - PURPOSE: The effectiveness of an opioid rotation to parenteral hydromorphone in
      advanced cancer patients has never been investigated. Therefore, the purpose of
      this study was to investigate the analgesic efficacy and side effects of
      parenteral hydromorphone on serious cancer-related pain. METHODS: We included 104
      consecutive advanced cancer patients who were extensively pretreated with
      opioids. They were rotated to parenteral hydromorphone because they failed to
      achieve adequate pain relief on other opioids. Pain intensity and side effects
      were daily assessed. The moment of adequate pain control was defined as the first
      of at least 2 consecutive days when the mean pain intensity at rest was <= 4 (on
      a 0-10 numeric rating scale) and side effects were tolerable. RESULTS: The
      reasons for rotation to parenteral hydromorphone were inadequate pain control
      with/without expected delivery problems due to high opioid dosages (n = 61) and
      intolerable side effects with persistent pain (n = 43). Adequate pain control was
      achieved in 86 patients (83%) within a mean of 5 days. Eight of 86 patients still
      had side effects, but these were scored as acceptable. The mean pain intensity at
      rest decreased from 5.4 [standard deviation (sd) = 2.1] to 2.4 (sd = 1.5; p <
      0.001). The median failure-free treatment period was 57 days and covered a
      substantial part of the median survival of 78 days in the responding patients.
      CONCLUSIONS: In advanced cancer patients with serious unstable cancer-related
      pain refractory to other opioids, continuous parenteral administration of
      hydromorphone often results in long-lasting adequate pain control and should be
      considered even after extensive pretreatment with opioids.

PMID- 21861201
TI  - The return trip effect: why the return trip often seems to take less time.
AB  - Three studies confirm the existence of the return trip effect: The return trip
      often seems shorter than the initial trip, even though the distance traveled and
      the actual time spent traveling are identical. A pretest shows that people indeed
      experience a return trip effect regularly, and the effect was found on a bus trip
      (Study 1), a bicycle trip (Study 2), and when participants watched a video of
      someone else traveling (Study 3). The return trip effect also existed when
      another, equidistant route was taken on the return trip, showing that it is not
      familiarity with the route that causes this effect. Rather, it seems that a
      violation of expectations causes this effect.

PMID- 21861202
TI  - In vitro and in silico strategies to identify OATP1B1 inhibitors and predict
      clinical drug-drug interactions.
AB  - PURPOSE: To establish in vitro and in silico models that predict clinical drug
      drug interactions (DDIs) with the OATP1B1 (SLCO1B1) transporter. METHODS: The
      inhibitory effect of 146 drugs and drug-like compounds on OATP1B1-mediated
      transport was studied in HEK293 cells. A computational model was developed to
      predict OATP1B1 inhibition. Concentration-dependent effects were investigated for
      six compounds; clinical DDIs were predicted by calculating change in exposure
      (i.e. R-values) in eight different ways. RESULTS: Sixty-five compounds were
      identified as OATP1B1 inhibitors at 20 MUM. The computational model predicted the
      test set with 80% accuracy for inhibitors and 91% for non-inhibitors. In vitro-in
      vivo comparisons underscored the importance of using drugs with known clinical
      effects as references. Thus, reference drugs, cyclosporin A, gemfibrozil, and
      fenofibrate, provided an inhibition interval to which three antiviral drugs,
      atazanavir, lopinavir, and amprenavir, could be compared and their clinical DDIs
      with OATP1B1 classified. CONCLUSIONS: Twenty-two new OATP1B1 inhibitors were
      identified, a predictive OATP1B1 inhibition in silico model was developed, and
      successful predictions of clinical DDIs were obtained with OATP1B1.

PMID- 21861203
TI  - A comparative evaluation of mono-, di- and triglyceride of medium chain fatty
      acids by lipid/surfactant/water phase diagram, solubility determination and
      dispersion testing for application in pharmaceutical dosage form development.
AB  - PURPOSE: To compare physiochemical properties of mono-, di- and triglycerides of
      medium chain fatty acids for development of oral pharmaceutical dosage forms of
      poorly water-soluble drugs using phase diagrams, drug solubility, and drug
      dispersion experiments. METHODS: Phase diagrams were prepared using a
      monoglyceride (glycerol monocaprylocaprate: Capmul MCM(r) EP), a diglyceride
      (glycerol dicaprylate) and two triglycerides (glycerol tricaprylate: Captex
      8000(r); caprylic/capric triglycerides: Captex 355 EP/NF(r)) in combination with
      a common surfactant (PEG-35 castor oil: Cremophor EL(r)) and water. Psuedoternary
      phase diagrams using mixtures of monoglyceride with either diglyceride or
      triglyceride were constructed to determine any potential advantage of using lipid
      mixtures. RESULT: The monoglyceride gave microemulsion (clear or translucent
      liquid) and emulsion phases, whereas di- and triglycerides exhibited an
      additional gel phase. Among individual mono-, di- and triglycerides, the oil-in
      water microemulsion region was the largest for the diglyceride. Gel phase region
      within diglyceride and triglyceride phase diagrams could be practically
      eliminated and microemulsion regions expanded by mixing monoglyceride with di- or
      tri-glycerides (1:1). Addition of a model drug, danazol, had no effect on
      particle sizes of microemulsions formed. Dispersion of drug in aqueous media from
      mixtures of mono- and diglyceride or mono- and triglyceride was superior to
      individual lipids. CONCLUSION: Systematic study on comparison of mono-, di- and
      triglyceride of medium chain fatty acids will help formulators select components
      for optimal lipid-based formulation.

PMID- 21861205
TI  - Validation of a modified algorithm for the identification of yeast isolates using
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOF MS).
AB  - Optimising antifungal treatment requires the fast and species-specific
      identification of yeast isolates. We evaluated a modified protocol for the rapid
      identification of clinical yeast isolates using matrix-assisted laser
      desorption/ionisation time-of-flight (MALDI-TOF) technology. First, we evaluated
      a simplified extraction procedure using 54 clinical yeast isolates. Second, we
      validated a new protocol with this simplified extraction procedure and lower
      identification threshold by analysing 167 isolates with either MALDI-TOF or
      conventional identification techniques. MALDI-TOF analysis with both the standard
      and short extraction procedure yielded identical identification results, although
      the log-scores were lower with the latter. With the modified protocol, 163/167
      (97.6%) isolates showed a correct identification as compared to conventional
      identification techniques. A total of 135 out of the 163 (82.8%) correct
      identifications showed log-scores above 1.7, which we considered as the minimum
      log-score for secure species identification. The rapid identification of clinical
      yeast isolates is crucial in patient management. The MALDI-TOF technique using a
      short extraction procedure can be an alternative for the labourious standard
      procedure, although the log-scores will be lower. The identification of clinical
      yeast isolates with the modified protocol is a practical and accurate alternative
      for conventional identification techniques. If the isolate shows a log-score
      below 1.7, the standard extraction procedure should be used.

PMID- 21861204
TI  - Evaluating child welfare policies with decision-analytic simulation models.
AB  - The objective was to demonstrate decision-analytic modeling in support of Child
      Welfare policymakers considering implementing evidence-based interventions.
      Outcomes included permanency (e.g., adoptions) and stability (e.g., foster
      placement changes). Analyses of a randomized trial of KEEP-a foster parenting
      intervention-and NSCAW-1 estimated placement change rates and KEEP's effects. A
      microsimulation model generalized these findings to other Child Welfare systems.
      The model projected that KEEP could increase permanency and stability,
      identifying strategies targeting higher-risk children and geographical regions
      that achieve benefits efficiently. Decision-analytic models enable planners to
      gauge the value of potential implementations.

PMID- 21861206
TI  - Association between P-glycoprotein and lymphoid antigen expression on myeloblasts
      versus therapy response and survival in de novo acute myeloid leukemia: long-term
      follow-up results.
AB  - P-glycoprotein (PGP) over-expression on malignant cells is associated with poor
      prognosis and treatment outcome due to the development of a multidrug resistance
      phenotype. In this study, we analyzed the correlation between expression of PGP
      and lymphoid antigens (Ly) on leukemic myeloblasts versus response to therapy and
      survival in acute myeloid leukemia (AML). Fifty-one consecutive patients, aged 16
      75 (median age 44.6 years), diagnosed with de novo AML between 1997 and 2000, and
      who received at least one induction chemotherapy course, were enrolled in the
      study. Expression of PGP on >= 10% of the myeloblasts (PGP(+)AML) at the time of
      diagnosis was observed in 21 patients (41%). The complete remission rate did not
      differ between PGP(+) (13/21) and PGP(-) (20/30) patients (62 vs. 67%). Twelve of
      the 51 patients (24%) were still alive after a median follow-up time of 11.5
      years (range 10.7-13.1). The Ly(+)AML patients showed significantly better
      overall survival compared with Ly(-)AML patients (8/18 vs. 4/33 patients alive at
      the last follow-up, P = 0.003). The subgroup of patients with co-expression of
      PGP and Ly also showed better overall survival compared with PGP(+)AML patients
      without Ly expression (4/8 vs. 0/13 patients alive at the last follow-up; P =
      0.04). Our results suggest that expression of lymphoid antigens on PGP(+)
      myeloblasts in AML can positively affect survival in AML patients, mainly due to
      a decreased relapse risk and better survival. Although the small number of
      patient may be perceived as a limitation of the study, the long follow-up period
      strengthens its value. Further prospective trials are needed to obtain more
      information concerning the association between PGP and lymphoid antigens in AML,
      which would put our results in their ultimate proper context.

PMID- 21861208
TI  - Dipyridamole reversal using theophylline during aminophylline shortage.

PMID- 21861207
TI  - Immunohistochemical detection of HSP27 and hnRNP K as prognostic and predictive
      biomarkers for colorectal cancer.
AB  - The present study was aimed at evaluating the expression of heat shock protein 27
      (HSP27) and heterogeneous nuclear ribonucleoprotein K (hnRNP K), two potential
      biomarkers of many cancers, in colorectal cancer (CRC) and their clinical
      significance. Expression of HSP27 and hnRNP K were investigated by
      immunohistochemistry (IHC) in a series of tissue microarrays containing 175
      primary colorectal cancers and their corresponding normal mucosa samples and
      matched with clinicopathological features and patient survival. HSP27 and hnRNP K
      displayed more frequent strong immunoreactivity in primary colorectal tumor
      samples compared with adjacent non-cancer tissue (P < 0.001). Increased
      cytoplasmic expression of HSP27 and hnRNP K were associated with tumor location
      (P = 0.032 and P < 0.001, respectively), poorer overall survival (P = 0.004 and P
      = 0.02, respectively) and to an unfavorable prognosis for CRC patients in
      multivariate analysis (P = 0.019 and P = 0.01, respectively). Their
      overexpression combination identified a subset of patients with definitively
      worse prognosis than any other combination (P < 0.001). Overexpression of HSP27
      and hnRNPK were independent markers of poor prognosis, and their combination
      predicted definitively adverse outcomes in CRC patients.

PMID- 21861209
TI  - Imaging of recurrent intramuscular granulomatous masses induced by depot
      injection of leuprorelin.
AB  - Leuprorelin is a luteinizing hormone-releasing hormone (LH-RH) agonist that is
      used as an agent of androgen deprivation in some patients with prostate cancer.
      When administered in depot form, local granulomatous reactions may occur at the
      injection site, which may mimic masses and which are associated with treatment
      failure. We present a patient who, over a period of 5 years, developed multiple
      intramuscular gluteal masses while receiving leuprorelin therapy via
      intramuscular depot injections; biopsy of one of the masses showed the specific
      histologic features of leuprorelin granuloma. To our knowledge, this entity has
      not been described in the radiology literature. Awareness of this entity is
      necessary to suggest the correct diagnosis in patients with a history of
      leuprorelin depot injections.

PMID- 21861210
TI  - Urban health inequities and the added pressure of climate change: an action
      oriented research agenda.
AB  - Climate change will likely exacerbate already existing urban social inequities
      and health risks, thereby exacerbating existing urban health inequities. Cities
      in low- and middle-income countries are particularly vulnerable. Urbanization is
      both a cause of and potential solution to global climate change. Most population
      growth in the foreseeable future will occur in urban areas primarily in
      developing countries. How this growth is managed has enormous implications for
      climate change given the increasing concentration and magnitude of economic
      production in urban localities, as well as the higher consumption practices of
      urbanites, especially the middle classes, compared to rural populations. There is
      still much to learn about the extent to which climate change affects urban health
      equity and what can be done effectively in different socio-political and socio
      economic contexts to improve the health of urban dwelling humans and the
      environment. But it is clear that equity-oriented climate change adaptation means
      attention to the social conditions in which urban populations live-this is not
      just a climate change policy issue, it requires inter-sectoral action. Policies
      and programs in urban planning and design, workplace health and safety, and urban
      agriculture can help mitigate further climate change and adapt to existing
      climate change. If done well, these will also be good for urban health equity.

PMID- 21861212
TI  - Lobular in-situ neoplasia on breast core needle biopsy: imaging indication and
      pathologic extent can identify which patients require excisional biopsy.
AB  - BACKGROUND: The surgical management of lobular in-situ neoplasia (LN) identified
      by core needle biopsy (CNB) is currently variable. Our institution has routinely
      excised LN on CNB since 2003, allowing for an unbiased assessment of upgrade
      rates. METHODS: Cases of LN on CNB, including atypical lobular hyperplasia (ALH)
      and lobular carcinoma-in-situ (LCIS), were identified in our pathology database.
      CNBs with concurrent pleomorphic LCIS, ductal carcinoma-in-situ (DCIS), and
      invasive carcinoma were excluded. Imaging indication/modality, biopsy indication,
      and radiologic concordance were determined. Pathology review included scoring
      total foci of LN in each CNB. Upgrade rates to invasive carcinoma or DCIS at
      excision were calculated. RESULTS: A total of 106 cases of LN (73 ALH and 33
      LCIS) on CNB were identified. Thirty patients had concurrent atypical ductal
      hyperplasia (ADH) and 76 had LN alone; 93 (88%) of the patients had available
      surgical follow-up (25 LN + ADH and 68 LN alone). The upgrade rate at excision
      was 16% (4 of 25) for LN + ADH and 4.4% (3 of 68) for LN alone. Patients with LN
      alone and discordant imaging, imaging for high-risk indications, or extensive
      LCIS (>4 foci) accounted for all the upgrades. Normal-risk patients who underwent
      biopsy to assess calcifications found by routine mammographic screening with LN
      alone did not result in upgrade. CONCLUSIONS: Women with a CNB diagnosis of LN
      for calcifications found on routine, normal-risk mammographic screening have a
      negligible risk of upgrade and may not require excisional biopsy. However,
      excisional biopsy should be offered to women undergoing imaging for other
      indications or with >4 foci of LN on CNB.

PMID- 21861211
TI  - New strategies in neuroprotection and neurorepair.
AB  - There are currently few clinical strategies in place, which provide effective
      neuroprotection and repair, despite an intense international effort over the past
      decades. One possible explanation for this is that a deeper understanding is
      required of how endogenous mechanisms act to confer neuroprotection. This mini
      review reports the proceedings of a recent workshop "Neuroprotection and
      Neurorepair: New Strategies" (Iguazu Falls, Misiones, Argentina, April 11-13,
      2011, Satellite Symposium of the V Neurotoxicity Society Meeting, 2011) in which
      four areas of active research were identified to have the potential to generate
      new insights into this field. Topics discussed were (i) metallothionein and other
      multipotent neuroprotective molecules; (ii) oxidative stress and their signal
      mediated pathways in neuroregeneration; (iii) neurotoxins in glial cells, and
      (iv) drugs of abuse with neuroprotective effects.

PMID- 21861213
TI  - Outcome and natural history of patients with stage IV colorectal cancer receiving
      chemotherapy without primary tumor resection.
AB  - BACKGROUND: There is a trend toward nonsurgical management of patients with
      nonobstructing metastatic (stage IV) colorectal cancer (CRC), although some will
      eventually undergo surgery. We examined patients with metastatic CRC who were
      managed with an intact primary tumor. METHODS: An institutional review board
      (IRB)-approved database was retrospectively reviewed. All patients presenting
      with stage IV CRC from 2000 to 2008 were identified and analyzed. RESULTS: Among
      the 255 patients identified, 112 were taken directly to the operating room for
      either primary tumor resection or colostomy/bypass. Among the remaining 143
      patients, 97 were managed without developing primary tumor-related symptoms, and
      14 (9.8%) developed significant primary tumor-related symptoms necessitating
      operative or endoscopic management. Of the patients who developed symptoms,
      oxaliplatin and/or irinotecan was used among 71.4% of patients, and bevacizumab
      in 50%. Forty-two patients in the series underwent elective primary tumor
      resection after receiving chemotherapy. No independent predictors for development
      of primary tumor-related symptoms could be identified after controlling for age,
      gender, tumor location, number of metastatic sites, and type of chemotherapy.
      Median overall survival was 34 months for those who underwent elective primary
      tumor resection after chemotherapy, and 16 months for those who failed
      chemotherapy and developed symptoms. CONCLUSIONS: Among patients with metastatic
      CRC without an initial indication for surgery, incidence of obstruction or
      perforation after initiating chemotherapy was low (9.8%). No predictors of
      primary tumor-related complications could be identified. Survival was favorable
      among the highly selected cohort of patients who underwent elective primary tumor
      resection after chemotherapy.

PMID- 21861215
TI  - Elevated serum YKL-40 level predicts poor prognosis in hepatocellular carcinoma
      after surgery.
AB  - BACKGROUND: YKL-40 is a member of the mammalian chitinase-like proteins. Elevated
      serum YKL-40 levels in patients with gastrointestinal cancer at time of diagnosis
      are associated with poor prognosis. The aim of this study is to evaluate the
      prognostic value of serum YKL-40 before surgery and during follow-up in
      hepatocellular carcinoma (HCC) patients receiving curative resection. METHODS:
      Serum YKL-40 levels were determined by enzyme-linked immunosorbent assay. Overall
      and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier
      method and compared by the log-rank test. A Cox proportional-hazards regression
      model was performed to identify independent prognostic factors. Median follow-up
      time was 35 months. RESULTS: Baseline serum YKL-40 was elevated in 56% of
      patients with HCC receiving curative resection. Patients with elevated serum YKL
      40 had significantly shorter overall and RFS than patients with normal serum YKL
      40 (P = 0.003 and P = 0.001, respectively). Multivariate Cox regression analyses
      indicated that baseline serum YKL-40 was an independent prognostic variable for
      overall and RFS [hazard ratio (HR) = 1.968, 95% confidence interval (CI): 1.093
      3.543, P = 0.024; HR = 1.891, 95% CI: 1.106-3.232, P = 0.020; respectively].
      After curative resection, high serum YKL-40 (log-transformed continuous variable)
      within 6 months predicted significantly poorer overall survival (HR = 3.003, 95%
      CI: 1.323-6.817, P = 0.009). CONCLUSIONS: This study indicated that serum YKL-40
      was an independent prognostic factor for overall and RFS in HCC patients
      receiving curative resection. Serial monitoring of serum YKL-40 after curative
      resection may provide prognostic information.

PMID- 21861214
TI  - Use of S-100B to evaluate therapy effects during bevacizumab induction treatment
      in AJCC stage III melanoma.
AB  - AIM: To investigate the feasibility of using bevacizumab to improve the survival
      of American Joint Committee on Cancer (AJCC) stage III melanoma patients, we
      investigated how a single bevacizumab treatment affected nodal disease and a
      panel of biomarkers in clinically fluorodeoxyglucose positron emission tomography
      (FDG-PET)/computed tomography (CT)-staged, stage III melanoma patients, prior to
      therapeutic lymph node dissection (TLND). METHODS: Four weeks before TLND, nine
      patients (median age 50, range 28.8-62.1 years; two male, seven female) with
      palpable lymph node metastases received 7.5 mg/kg bevacizumab. Before and after
      this treatment, all patients were assessed by measurements of the maximum
      standardized uptake value (SUVmax) by FDG-PET scan, and serum S-100B and lactate
      dehydrogenase (LDH). After TLND, the dissection specimen was analyzed for number
      of removed lymph nodes, number of metastatic lymph nodes, and tumor necrosis.
      RESULTS: Median follow-up was 15.5 (2.2-32.9) months. Histopathological analysis
      revealed tumor necrosis in six patients, of whom five had an S-100B decline and
      one had an unchanged S-100B level after bevacizumab. The other three patients
      showed an S-100B increase and no necrosis. Tumor necrosis was correlated with S
      100B decrease (P = 0.048). No association was found between necrosis and the
      markers SUVmax and LDH. No wound healing disturbances were encountered.
      CONCLUSION: Tumor necrosis in dissection specimens was associated with declining
      S-100B levels, while elevated S-100B was only found in cases with no necrosis.
      Bevacizumab might be useful in treating AJCC stage III melanoma patients prior to
      TLND, and S100-B appears to be a useful marker for assessment of treatment
      effects.

PMID- 21861216
TI  - Esophagectomy with extended lymphadenectomy for submucosal esophageal cancer:
      long-term outcomes and prognostic factors.
AB  - BACKGROUND: There are controversies regarding the extent of lymphadenectomy
      necessary during the course of esophagectomy for submucosal esophageal cancer.
      The purpose of this study was to examine the long-term outcomes after
      esophagectomy with extended lymphadenectomy in patients with submucosal
      esophageal cancer and to investigate the prognostic factors in these patients.
      MATERIALS: A prospectively maintained database identified 105 previously
      untreated patients with submucosal esophageal cancer who underwent transthoracic
      esophagectomy with three-field or two-field lymphadenectomy. Median follow-up was
      101 months. RESULTS: All patients received R0 resection. Ninety-eight patients
      had squamous cell carcinoma, and seven had adenocarcinoma. Lymph node metastasis
      was present in 38 patients (36.2%), of whom 9 patients (23.7%) had positive
      cervical nodes. Thirty-five patients (33.3%) had other primary malignancies. The
      overall 5- and 10-year survival rates were 74.4 and 57.4%, respectively. The
      cause of death was recurrent disease in 16 patients, other malignancy in 12, and
      noncancer-related disease in 18. Univariate analyses demonstrated that other
      primary malignancy (P = 0.0041), poor differentiation (P = 0.0203), and
      angiolymphatic invasion (P = 0.0347) significantly affected overall survival.
      There was no difference in survival between patients with lymph node metastasis
      and those without (P = 0.9809). Multivariate analysis found other primary
      malignancy to be the only independent prognostic factor (hazards ratio, 2.295;
      95% confidence interval, 1.201-4.386; P = 0.0119). CONCLUSIONS: Esophagectomy
      with extended lymphadenectomy for submucosal esophageal cancer results in 57.4%
      survival at 10 years. Other primary malignancy is the only independent predictor
      affecting long-term survival. Patients should be examined rigorously for other
      primary malignancy as well as recurrent disease during long-term follow-up.

PMID- 21861218
TI  - Re: Neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer
      patients with peritoneal dissemination.

PMID- 21861219
TI  - A review of current management of brain metastases.
AB  - BACKGROUND: The brain metastasis (BM) represents one of the most common and
      refractory malignancies worldwide with a rising incidence in all countries. It is
      generally believed that once a BM has developed, this disease cannot be cured and
      has a poor prognosis. The challenges of managing this tumor include diagnosis and
      selective treatment options. In addition, patients with BM frequently have
      greater expectations of the current therapy outcomes, which hope to get long-term
      survival and good quality of life. METHODS: This is a review of current clinical
      practice based on an exhaustive literature search of PubMed, Embase, and Google
      Scholar. A series of case studies is presented to provide outcomes of the
      effective management in BMs that have required treatment for the terminal stage
      of patients with cancer, and makes recommendations for future practice. RESULTS:
      Current technical advances have been made in the diagnosis and treatment of BM.
      After surgery, radiotherapy, or stereotactic radiosurgery, and for some cases
      additional systemic chemotherapy for the primary cancer, most patients experience
      meaningful symptom relief, improved quality of life and longer survival time. An
      evidence-based summary of recommendations has been produced to guide
      neurosurgeons and oncologists in managing this particular group of patients.
      CONCLUSIONS: On the basis of the available data, this treatment approach for well
      selected patients is currently not recommended in the treatment of BMs except in
      experienced medical centers. Clinical judgment is made balancing surgical,
      radiotherapy, chemotherapy and management principles to advocacy the best therapy
      outcome.

PMID- 21861220
TI  - Anterior-entry abdominoperineal resection: a variation in the method of perineal
      dissection.
AB  - BACKGROUND: For patients with rectal cancer, there is a greater risk of a
      positive radial margin or local tumor recurrence when an abdominoperineal versus
      low anterior resection is performed, or when tumors are in an anterior versus
      nonanterior location. In response, clinical leaders have encouraged perineal
      dissection in the prone position or in concert with a coccygectomy. We describe
      anterior-entry abdominoperineal resection, which may minimize the need for such
      maneuvers and negative patient outcomes. METHODS: Anterior-entry abdominoperineal
      resection was provided by one surgeon to 10 patients over an 18-month period.
      Pelvic dissection used total mesorectal excision techniques. Anteriorly, in men,
      the perineal dissection occurred between the external anal sphincter and the
      bulbospongiosus and transversus perinei superficialis muscles. Initial entry into
      the pelvis occurred anteriorly under direct vision. Rectal specimen quality was
      graded out of 5 using Quirke methods. RESULTS: There were 8 male and 2 female
      subjects with a median age of 65 years. Eight of 10 tumors had some component of
      an anterior location. Seven patients received preoperative radiation. The radial
      margin was positive in 1 case. Median Quirke score for quality of the surgical
      specimen was 5 of 5. CONCLUSIONS: Anterior-entry abdominoperineal resection
      follows anatomic planes in the perineum and demands initial entry into the pelvis
      anteriorly and under direct vision. It may minimize rates of positive radial
      margins, may be especially suited for tumors with a locally advanced anterior
      component, and in many patients may avoid the need for perineal dissection in the
      jackknife position.

PMID- 21861221
TI  - Focused ultrasound ablation for the treatment of breast cancer.
AB  - Advances in technology and changes in our understanding of tumor biology have
      allowed breast cancer treatment to evolve toward less disfiguring procedures.
      Noninvasive ablative therapy is a natural continuation of this trend. The
      following paper presents the concepts underpinning focused ultrasound ablation
      therapy for the treatment of breast cancer and reviews the investigative
      experience to date in the evaluation of this promising technique.

PMID- 21861222
TI  - Preoperative predictors of nipple-areola complex involvement for patients
      undergoing mastectomy for breast cancer.
AB  - BACKGROUND: Proper patient selection is important for nipple-sparing mastectomy,
      and we aimed to identify preoperative factors predictive of pathologic nipple
      areola complex (NAC) involvement to assist with surgical planning. METHODS: We
      retrospectively reviewed a prospectively collected database of patients who
      underwent mastectomy for DCIS or invasive breast cancer at a single institution.
      Cases with NAC involvement, NAC(+), were compared with those without NAC
      involvement, NAC(-). Multivariate logistic regression analysis was performed to
      determine preoperative factors independently predictive of NAC involvement.
      RESULTS: A total of 238 standard, 107 skin-sparing, and 47 nipple-sparing
      mastectomies were performed, and the NAC was pathologically involved in 16% (N =
      62). Clinical NAC involvement, as determined by patient symptoms or physical
      exam, was present in 61% of NAC(+) but only 14% of NAC(-) cases (P < .0001) and
      carried a 92% negative predictive value (NPV). Preoperative imaging involved the
      NAC in 38% of NAC(+) but only 4% of NAC(-) cases (P < .0001) and carried an 89%
      NPV. NAC(+) tumors were larger, with mean size 3.3 cm versus 2.5 cm for NAC(-)
      tumors (P = .024). The mean tumor-to-nipple distance was 2.0 cm for NAC(+) versus
      4.7 cm for NAC(-) tumors (P < .0001). On multivariate analysis, independent
      predictors of NAC involvement were the presence of clinical NAC involvement (odds
      ratio [OR] 5.11, 95% confidence interval [95% CI] 2.53-10.35) and imaging
      involvement of the NAC (OR 5.82, 95% CI 2.43-13.94). CONCLUSIONS: Clinical and
      imaging abnormalities at the NAC are the only independent preoperative predictors
      of NAC pathology, and the absence of these factors conveys a low probability of
      NAC involvement.

PMID- 21861223
TI  - Evaluation of the MD Anderson Prognostic Index for local-regional recurrence
      after breast conserving therapy in patients receiving neoadjuvant chemotherapy.
AB  - BACKGROUND: We previously developed a prognostic index for assessing local
      regional recurrence (LRR) risk in patients undergoing breast conservation therapy
      (BCT) after neoadjuvant chemotherapy. The prognostic index assigns a point for
      each of the following variables: clinical N2/N3 disease, lymphovascular invasion,
      residual pathologic tumor size >2 cm, and multifocal residual disease on
      pathology. The current study was undertaken to evaluate this prognostic index in
      an independent cohort. METHODS: We identified 551 patients treated from 2001 to
      2005 with neoadjuvant chemotherapy, mastectomy or BCT, and radiation. These
      patients were not used in the original development of the prognostic index.
      Outcomes were stratified by prognostic index. The 5-year LRR-free survival was
      calculated using the Kaplan-Meier method, and differences were compared using the
      log-rank test. RESULTS: For patients undergoing BCT, the 5-year LRR-free survival
      rates were 92, 92, 84, and 69% when the prognostic index was 0 (n = 91), 1 (n =
      82), 2 (n = 38), or 3-4 (n = 13) (P = 0.01). The 5-year LRR-free survival rates
      were similar between patients undergoing mastectomy or BCT when the prognostic
      index score was 0, 1, or 2. When the prognostic index score was 3-4, the 5-year
      LRR-free survival was significantly lower for patients treated with BCT compared
      with mastectomy (69 vs. 93%, P = 0.007). CONCLUSION: The previously developed
      prognostic index was successful in stratifying patients with respect to LRR in an
      independent cohort undergoing BCT after neoadjuvant chemotherapy. The prognostic
      index can be used to identify patients at high risk for LRR who may be considered
      for more extensive surgery or enrollment into clinical trials evaluating novel
      strategies for local-regional control.

PMID- 21861224
TI  - Focus on extralevator perineal dissection in supine position for low rectal
      cancer has led to better quality of surgery and oncologic outcome.
AB  - BACKGROUND: After abdominoperineal excision (APE), the presence of tumor cells in
      the circumferential resection margin (R1) and iatrogenic tumor perforations are
      still frequent and result in an increased rate of local recurrences. In this
      study, a standardized supine APE with an increased focus on the perineal
      dissection (sPPD) is compared to the customary supine APE. METHODS: From 2000 to
      2010, a total of 246 patients underwent APE for rectal cancer (sPPD and customary
      supine APE). All patients were staged with preoperative magnetic resonance
      imaging (MRI) and received neoadjuvant treatment (n = 203) when margins were
      involved or threatened (cT3 + and T4). As a result of a quality improvement
      program in 2006, the surgical technique was modified: it became standardized,
      emphasis was placed on the perineal dissection, and pelvic dissection was limited
      to avoid false routes when following the total mesorectal excision planes deep
      into the pelvis. RESULTS: Overall, the percentage of involved circumferential
      resection margins (CRMs) was 10%. In the period before introducing sPPD, the R1
      percentages for cT0-3 and cT4 tumors were 6.8 and 30.2%, compared to 2.2 and 5.7%
      after introduction of sPPD (P = 0.001). Risk factors for R1 resection were
      preoperative T4 tumors (14.9%, P = 0.011), tumor perforation (33.3%, P = 0.002),
      fistulating tumors (35.7%, P = 0.002), mucus-producing tumors (23.1%, P = 0.006),
      or bulky tumors (66.7%, P < 0.001). CONCLUSIONS: The objective of surgical
      treatment of low rectal cancer is to obtain negative resection margins and
      subsequently reduce the risk of local recurrence. A combination of the
      appropriate preoperative treatment and standardized surgical technique such as
      sPPD can achieve this goal.

PMID- 21861225
TI  - Simple enucleation versus radical nephrectomy in the treatment of pT1a and pT1b
      renal cell carcinoma.
AB  - BACKGROUND: Simple tumor enucleation (TE) showed excellent oncologic results in
      large retrospective series. No study has compared oncologic outcomes after TE and
      radical nephrectomy (RN) for the treatment of pT1 renal cell carcinoma (RCC). The
      aim of the present study is to compare the oncologic outcomes after TE and RN in
      pT1 RCCs. METHODS: We retrospectively analyzed 475 patients who underwent TE or
      RN for pT1 RCC, N0, M0, between 1995 and 2007. TE was performed in 332 patients
      and RN in 143. Local recurrence, progression-free survival (PFS), and cancer
      specific survival (CSS) were the main outcomes of this study. The Kaplan-Meier
      method was used to calculate survival functions, and differences were assessed
      with the log rank statistic. Univariate and multivariate Cox regression models
      were also used. RESULTS: The 5- and 10-year PFS estimates were 91.3 and 88.7%
      after RN and 95.3 and 92.8% after TE (P = NS), respectively. The 5- and 10-year
      CSS estimates were 92.1 and 89.4% after RN and 94.4% (5- and 10-year CSS) after
      TE (P = NS), respectively. No statistically significant differences between RN
      and TE were found after adjusting CSS probabilities according to age at surgery,
      grade, stage, or clear cell subtype. Surgical treatment was not a predictor of
      PFS or CSS by both univariate and multivariate analyses. The potential limitation
      of this study is that the data originate from a retrospective review.
      CONCLUSIONS: TE can achieve oncologic results similar to those of RN for the
      treatment of pT1 RCCs, provided tumors are carefully selected on the basis of
      their safe and complete removal.

PMID- 21861227
TI  - XPC mRNA level may predict relapse in never-smokers with non-small cell lung
      cancers.
AB  - BACKGROUND: Disease recurrence and distant metastasis are the major causes of
      death in resected non-small cell lung cancer (NSCLC). The prognostic marker for
      never-smokers with this disease remains to be identified. To improve patient
      outcome, establishing an adjacent molecular marker to predict relapse of NSCLC in
      never-smokers is needed. METHODS: Three hundred two lung tumors from NSCLC
      patients and normal lung tissues from 68 noncancer subjects were enrolled to
      evaluate XPC (xeroderma pigmentosum group C) mRNA expression by quantitative real
      time reverse transcriptase polymerase chain reaction. Receiver operating
      characteristic curve analysis was used to search for a feasible cutoff point of
      XPC mRNA levels for predicting recurrence-free survival. Of the 326 patients, 214
      were confirmed as only receiving surgical resection. Kaplan-Meier and
      multivariate Cox regression analysis were used to assess the prognostic value of
      XPC mRNA level in lung tumors from patients who only received surgical resection.
      RESULTS: Receiver operating characteristic curve analysis indicated 30.28 as a
      cutoff point, and thus 150 and 64 tumors with low- and high-XPC mRNA expression
      were categorized in this study population. Low-XPC mRNA appeared with more
      frequency in never-smokers and in late-stage (stage II-III) disease than smokers
      and early-stage disease (stage I). Kaplan-Meier analysis indicated that patients
      with low-XPC mRNA had shorter recurrence-free survival than that found in never
      smokers (P = 0.002), but not in smokers (P = 0.296). Cox regression analysis
      further revealed that low-XPC mRNA may independently predict relapse in lung
      cancer of never-smokers (hazard ratio 2.34, 95% confidence interval 1.21-4.51, P
      = 0.011). CONCLUSIONS: Low-XPC mRNA may predict relapse in lung cancer patients
      who are never-smokers.

PMID- 21861226
TI  - Socioeconomic and racial differences in treatment for breast cancer at a low
      volume hospital.
AB  - PURPOSE: Population-based studies have revealed higher mortality among breast
      cancer patients treated in low-volume hospitals. Other studies have demonstrated
      disparities in race and socioeconomic status (SES) in breast cancer survival. The
      purpose of our study was to determine whether nonwhite or low-SES patients are
      disproportionately treated in low-volume hospitals. METHODS: A population-based
      cohort of 2,777 Medicare breast cancer patients who underwent breast cancer
      surgery in 2003 participated in a survey study examining breast cancer outcomes.
      Information was obtained from survey responses, Medicare claims, and state tumor
      registry data. RESULTS: On univariate analysis, patients treated at low-volume
      hospitals were less likely to be white, less likely to live in an urban location,
      and more likely to have a low SES with less social support and live a greater
      distance from a high-volume hospital. Education, marital status, total household
      income, having additional insurance besides Medicare, population density of
      primary residence, and tangible support were associated with distance to the
      nearest high-volume hospital. On multivariate analysis, the independent
      predictors of treatment at a low-volume hospital were being nonwhite (P = 0.003),
      having a lower household income (P < 0.0001), residence in a rural location (P =
      0.01), and living a greater distance from a high-volume hospital (P < 0.0001).
      CONCLUSIONS: In this large population-based cohort, women who were poorer,
      nonwhite, and who lived in a rural location or at a greater distance from a high
      volume hospital were more likely to be treated at low-volume hospitals. These
      differences may partially explain racial and SES disparities in breast cancer
      outcomes.

PMID- 21861228
TI  - Association of FANCC and PTCH1 with the development of early dysplastic lesions
      of the head and neck.
AB  - BACKGROUND: Alteration of chromosome 9q22.3 region is an early and frequent event
      in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to
      understand the association of candidate tumor suppressor genes PHF2, FANCC,
      PTCH1, and XPA located in this region in the development of HNSCC. METHODS: The
      alterations (deletion, promoter methylation, mutation, expression) of these genes
      were analyzed in 65 dysplastic head and neck lesions and 84 primary HNSCC
      samples. Clinicopathologic correlations were made with alterations of the genes.
      RESULTS: Overall alterations (deletion, promoter methylation) of FANCC and PTCH1
      were high in mild dysplasia and comparable in subsequent stages of tumor
      progression. However, PHF2 alteration was low in mild dysplasia, but increased in
      moderate and severe dysplasias. Alterations (deletion, promoter methylation) of
      FANCC and PTCH1 showed association with each other. Two novel mutations in GLI
      binding sites of PTCH1 promoter and a novel microsatellite marker hmPTCH1 with
      four alleles at immediate upstream of the gene were identified. In a case-control
      study, the (CGG)7 allele of hmPTCH1 was found to be susceptible for HNSCC
      development. Concordance was seen in the expression (RNA, protein) of these genes
      with their molecular alterations. CONCLUSIONS: Alterations of FANCC and PTCH1
      could be used as molecular marker for early diagnosis and prognosis of HNSCC.

PMID- 21861229
TI  - Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are a rare form of
      soft tissue sarcoma with few studies reporting on patient outcomes and prognostic
      variables. METHODS: A retrospective review of 175 patients diagnosed with MPNST
      from 1985 to 2010 was performed. Patient, tumor, and treatment characteristics
      were evaluated to identify prognostic variables. RESULTS: The median age of our
      study population was 44 years, and 51% were female. Median tumor size was 6 cm,
      and 61% of patients had high-grade tumors. Tumors were most commonly located on
      the extremities (45%), then trunk (34%) and head/neck (19%). The majority of
      patients underwent surgical resection (95%) and adjuvant treatment with
      chemotherapy (6%), radiation (42%) or both (22%). Margin status was R0 in 69%, R1
      in 2%, R2 in 9%, and unknown in 20%. The local recurrence rate was 22%, and 5-
      and 10-year disease-specific survival (DSS) were 60% and 45%, respectively. On
      univariate analysis, no predictors for local recurrence were identified. Tumor
      size >= 5 cm, high tumor grade, tumor location, presence of neurofibromatosis
      type 1, local recurrence, and adjuvant chemotherapy were all associated with DSS.
      On multivariate analysis, size >= 5 cm [hazard ratio (HR)= 6.1, 95% confidence
      interval (CI) 1.5-25.0], local recurrence (HR = 4.4, 95% CI 1.7-11.4), high tumor
      grade (HR = 3.8, 95% CI 1.1-13.2), and truncal location (HR = 3.7, 95% CI 1.1
      12.7) were poor prognostic indicators for DSS. CONCLUSIONS: High tumor grade and
      tumor size >= 5 cm predict adverse DSS for MPNST. In the context of a
      multidisciplinary treatment regimen, local recurrence and survival outcomes at 5
      and 10 years were better than previously reported for MPNST.

PMID- 21861230
TI  - A look into the ductoscope: its role in pathologic nipple discharge.
AB  - OBJECTIVE: Mammary ductoscopy allows direct visualization of the ductal system
      and a method for directed excision and pathologic diagnosis. We reviewed our
      experience with mammary ductoscopy in the evaluation of pathologic nipple
      discharge. METHODS: We reviewed all patients who underwent ductoscopy for
      pathologic nipple discharge at our institution from 2006-2010. All procedures
      were performed by a single surgeon. Data included patient and imaging
      characteristics, indications, operative findings, and pathologic outcomes.
      Descriptive statistics were used for data summary. RESULTS: During the study
      period, 121 patients underwent ductoscopy and directed duct excision for
      pathologic nipple discharge, including 66 (55%) with bloody discharge. Breast
      imaging [mammography, ultrasound, and/or magnetic resonance imaging (MRI)]
      revealed BIRADS category I/II/III findings in 112 (93%), BIRADS category IV
      findings in 6 (5%), and was unknown in 3 (2%) patients. Final pathology revealed
      papillomas in 64 (53%) patients, duct ectasia and associated benign findings in
      48 (40%) patients, ductal carcinoma in situ (DCIS) in 7 (6%) patients, and
      atypical ductal hyperplasia in 2 (1%) patients. None of the patients with DCIS
      underwent preductoscopy MRI, but all had BIRADS category I/II/III breast imaging.
      The extent of DCIS identified by ductoscopy and subsequent surgical excision
      ranged from <1 cm to 10 cm (median 3 cm). CONCLUSIONS: The majority of patients
      with pathologic nipple discharge have benign nonproliferative findings or benign
      papillomas. Although atypia and malignancy were diagnosed in only 7% of patients
      who underwent ductoscopy for pathologic nipple discharge, there were no routine
      imaging findings indicative of these diagnoses preoperatively.

PMID- 21861231
TI  - Sensitivity of axillary specimen x-ray to predict nodal count and positivity.
AB  - BACKGROUND: The number of examined axillary lymph nodes (ALN) has been proposed
      as an indicator of prognosis along with quality and adequacy in breast cancer
      surgery. The purpose of this study was to examine the utility of imaging axillary
      specimens with x-ray (lymphogram) to determine the number of lymph nodes. We
      sought to determine the sensitivity and specificity of a lymphogram in
      identifying nodal positivity. METHODS: Patients who underwent sentinel lymph node
      (SLN) and axillary lymph node dissections (ALND) were prospectively accrued to
      this double-blinded, single-institution trial from December 2009 to January 2011.
      A single physician interpreted all lymphograms for the number of ALNs and
      positivity determined by size, spiculations, irregularities, and calcifications.
      RESULTS: Twenty female (age 50.8 +/- 14.3 years) patients were accrued to the
      study. The lymphogram located more lymph nodes compared with pathology in 11 of
      16 cases (68.8%). In these 11 cases, lymphogram identified 170 nodes and the
      pathologist located 132 (77.6%). Of the 16 ALND specimens, 6 were from patients
      naive to chemotherapy and averaged 13.8 +/- 6.6 nodes; 10 were from neoadjuvant
      chemotherapy patients and had an average number of 14.9 +/- 7.4 nodes. In
      neoadjuvant chemotherapy patients, sensitivity of the lymphogram to detect nodal
      positivity was 91.7% and specificity was 33.3%. CONCLUSIONS: This study
      demonstrated that lymphogram accurately identifies nodal count. This can be used
      for documentation of an adequate ALND for reimbursement. Furthermore, there may
      be potential value of lymphogram in intraoperative determination of nodal
      positivity.

PMID- 21861232
TI  - Ultrasound-guided lumpectomy for palpable breast cancers.
AB  - BACKGROUND: We sought to determine the re-excision rate following lumpectomy for
      palpable breast cancers using intraoperative ultrasound (US). A secondary aim was
      to investigate the impact on surgical decision-making. METHODS: We identified 73
      women who underwent US-guided lumpectomy for palpable breast cancer between 2006
      and 2010. A cohort of 124 women who underwent palpation-guided lumpectomy was
      used for a comparison group. Data included patient demographics, tumor
      characteristics, intraoperative findings, and pathologic outcomes. Descriptive
      statistics were used for data summary and compared by chi-square or t test, as
      appropriate. RESULTS: A total of 73 women underwent US-guided lumpectomy, and 124
      women underwent palpation-guided lumpectomy (median age 55 years). Patients
      undergoing palpation-guided lumpectomy had smaller tumors that were more likely
      to be HER2/neu amplified compared with patients undergoing US-guided lumpectomy
      (P < 0.05 for each). There were no differences between the 2 groups with respect
      to patient age, tumor grade, and estrogen/progesterone receptor status (P > 0.05
      for each). Re-excision rates were similar in both groups [17 (23%) in the US
      group versus 31 (25%) in the palpation group; P > 0.05]. In the US group, 45
      patients (62%) had additional shave margins taken based on US interrogation of
      the specimen, and 12 patients (16%) were spared a 2nd procedure based on the use
      of intraoperative US. CONCLUSIONS: Although palpable breast cancers can be
      excised based on direct palpation or needle localization, we believe that US
      guidance provides an excellent tool to aid the breast surgeon. Only 10% of
      patients had a positive margin on final pathology as a result, and the overall re
      excision rate was acceptable.

PMID- 21861233
TI  - Distance of breast cancer from the skin and nipple impacts axillary nodal
      metastases.
AB  - BACKGROUND: Lymphatic drainage of the breast is via subareolar and dermal
      lymphatics. The aim of this study was to determine whether distance of breast
      cancers from the skin and/or distance from the nipple impacts the likelihood of
      axillary nodal metastases. METHODS: A retrospective review was performed of
      sonographically visible T1 and T2 breast cancers with breast and axillary surgery
      performed at Mayo Clinic, Rochester, MN. Distance of tumor from the nipple was
      reviewed. Ultrasounds were reviewed to measure the distance of tumor from the
      skin. RESULTS: Data were collected on 233 eligible T1 or T2 breast cancers, of
      which 177 (76%) were node negative and 56 (24%) were node positive. On
      multivariable analysis, tumor stage and lymphovascular invasion, as well as
      decreasing distance of the tumor from the nipple and decreasing distance of the
      tumor from the skin, were significantly associated with axillary lymph node
      positivity. Each 1-cm decrease in the distance of the tumor from the nipple was
      associated with a 23% increased likelihood of positive lymph nodes (odds ratio
      1.23; P = .003). Each 1-mm decrease in the distance of the tumor from the skin
      was associated with a 15% increased likelihood of positive lymph nodes (odds
      ratio 1.15; P = .003). CONCLUSION: T1 and T2 breast cancers located closer to the
      skin and those located closer to the nipple have a higher incidence of metastases
      to axillary lymph nodes. Distance from the skin and distance from the nipple
      should be considered when estimating a patient's likelihood of axillary nodal
      positivity.

PMID- 21861234
TI  - Cost-effectiveness analysis of routine frozen-section analysis of breast margins
      compared with reoperation for positive margins.
AB  - BACKGROUND: Negative margins are associated with decreased local recurrence after
      lumpectomy for breast cancer. A 2nd operation for re-excision of positive margins
      is required with rates varying from 15 to 50%. At our institution we routinely
      use frozen-section analysis of all margins to minimize rates of 2nd operations.
      The aim of this study was to evaluate the cost/benefit of routine frozen-section
      analysis. METHODS: A decision tree was built to compare 2 strategies: (A)
      lumpectomy without frozen section and a 2nd operation for positive margin(s)
      versus (B) lumpectomy with intraoperative frozen-section analysis and a 2nd
      operation for positive margin(s). For strategy A the rate of positive margins and
      reoperation were varied from 15 to 50%. For strategy B, a 2nd operation rate of
      3% was used. Review of our institutional experience demonstrates an
      intraoperative re-excision of at least 1 margin in 57% of cases performed with
      frozen-section support. RESULTS: The cost to provider (i.e., institution) per
      patient resected to negative margins for strategy A ranged from $4835 to $6306.
      Average weighted cost of strategy B was $5708. Strategy B was less expensive when
      the reoperation rate was above 36%. The cost to payor (i.e., Medicare) for
      strategy A ranged from $3577 to $4665. Average weighted cost for strategy B was
      $3913. Strategy B was less expensive when the re-excision rate was above 26%.
      CONCLUSION: Routine use of frozen-section analysis of lumpectomy margins
      decreases reoperation rates for margin control; therefore, the cost to provider
      and payor can be cost effective.

PMID- 21861235
TI  - Overexpression of RhoGDI2 correlates with tumor progression and poor prognosis in
      colorectal carcinoma.
AB  - BACKGROUND: RhoGDI2 has been identified as a regulator of tumor metastasis but
      its role in cancer remains controversial. The aims of this study were to analyze
      the function of RhoGDI2 in colorectal carcinoma (CRC), and to determine its
      possible signaling pathway in CRC. METHODS: The expression of RhoGDI2 was
      detected in CRC cell lines, and 20 matched pairs of fresh CRC tissues, and 120
      cases of clinical paraffin-embedded CRC tissues by real-time RT-PCR, Western
      blot, RT-PCR, or immunohistochemistry. The levels of activations of p-PI3K, p
      Akt, p-MAPK, and p-MEK were then examined in RhoGDI2-overexpressing cells by
      Western blot. A series of assays were finally performed to evaluate the effect of
      RhoGDI2 on CRC cell behaviors in vitro. RESULTS: RhoGDI2 expression was higher in
      highly metastatic CRC cell lines than in lowly metastatic ones. RhoGDI2
      expression was up-regulated in CRC or lymphatic metastatic tissues relative to
      normal mucosa (P < 0.05). RhoGDI2 expression was correlated strongly with tumor
      size, differentiation, and Duke's stage (P < 0.05). Patients with lower RhoGDI2
      expression had better overall survival (P = 0.012), and RhoGDI2 could predict
      prognosis only in patients with early-stage disease. High levels of activations
      of p-PI3K and p-Akt were observed in RhoGDI2-overexpressing cells. LY294002
      inhibitor could abrogate the activation of PI3K/Akt pathway in those cells. Over
      expression of RhoGDI2 enhanced CRC cell proliferation, motility, and invasion in
      vitro. CONCLUSIONS: Over-expression of RhoGDI2 is associated with poor overall
      survival in CRC patients, especially those presenting in early-stage. RhoGDI2
      contributes to cell proliferation, motility, and invasion of CRC, at least in
      part, by activating the PI3K/Akt pathway.

PMID- 21861236
TI  - Technical controversies in laparoscopic sleeve gastrectomy.
AB  - Laparoscopic sleeve gastrectomy is a recently developed technique for treating
      morbid obesity. Since it is a simple procedure, many bariatric surgeons have
      adopted it in recent years with good results. However, there is still no standard
      procedure across different surgical teams. We will discuss the more controversial
      aspects of the surgical technique: the size of the bougie, the beginning of the
      distal section, the section shape at the gastroesophageal junction, the necessity
      and manner of reinforcing the staple line, and the routine use of intraoperative
      leak testing.

PMID- 21861237
TI  - HPV vaccination uptake among Cambodian mothers.
AB  - Women of Southeast Asian descent have higher cervical cancer incidence rates than
      any other group. Widespread use of HPV vaccination could prevent up to 70% of
      cervical cancers. There is little published information addressing HPV
      vaccination uptake among Asian Americans. We conducted a survey of Cambodian
      women with daughters who were age-eligible for HPV vaccination. Survey items
      addressed HPV vaccination barriers, facilitators, and uptake. Only 26% of the
      survey participants reported any of their age-eligible daughters had received
      vaccination, and only 40% reported a previous physician recommendation for
      vaccination. Higher levels of vaccine uptake were strongly associated with having
      received a doctor's recommendation for vaccination (p < 0.001) and having asked a
      doctor for vaccination (p = 0.002). HPV vaccine uptake was relatively low in our
      Cambodian study group. Educational initiatives should encourage health care
      providers who serve Cambodian families to recommend HPV vaccination and empower
      Cambodian mothers to ask their daughters' doctors for vaccination.

PMID- 21861238
TI  - A performance measurement tool for cancer patient information and satisfaction.
AB  - Cancer programs need to monitor their performance related to providing patient
      information. A new measurement tool was designed to gather indicator data
      concerning the importance of selected information topics and satisfaction with
      what information they had received. Based on a mixed sample of 540 cancer
      patients, the reliability of the importance and satisfaction scales were
      acceptable (Cronbach's alpha 0.89 and 0.92, respectively). The newly designed
      Cancer Information Importance/Satisfaction Scale is a reliable measure and can be
      easily applied as a performance indicator.

PMID- 21861239
TI  - Religiosity is an important part of coping with grief in pregnancy after a
      traumatic second trimester loss.
AB  - Women (n = 15) who were pregnant after a traumatic late pregnancy loss
      (termination because of fetal death or serious anomalies) completed psychometric
      screening tests and scales, including the Perinatal Grief Scale (PGS), the Impact
      of Event Scale (IES), the Duke Depression Inventory (DDI), the Generalized
      Anxiety Disorder-7 (GAD), and the Hoge Scale for Intrinsic Religiosity (IR).
      Despite a mean elapsed time since the prior loss of 27 (range, 7-47) months, half
      (7/15, 47%) of the combined groups had high levels of grief on the PGS. Multiple
      positive scores on psychometric tests were frequent: Sixty percent (9/15) had
      high scores on the PGS Active Grief subscale or on the IES. Forty percent (6/15)
      had a high score on the DDI, and 17% (3/15) on the GAD. IR scores significantly
      and negatively correlated with scores on the Despair subscale of the PGS. The
      results from this pilot study suggest that high levels of grief and PTS symptoms
      are significant problems for pregnant women who have suffered late loss of a
      wanted pregnancy. Religiosity may play an important part in maternal coping
      during these stressful pregnancies.

PMID- 21861240
TI  - Are genetic counselors and GLBT patients "on the same page"? An investigation of
      attitudes, practices, and genetic counseling experiences.
AB  - Gay, lesbian, bisexual, and transgender (GLBT) individuals comprise a growing
      patient population in genetic counseling, yet literature on working with this
      population is scarce. This study sought to investigate GLBT patient experiences
      in genetic counseling and genetic counselor attitudes and practices when
      counseling GLBT patients. Twenty-nine GLB individuals who had previously
      participated in genetic counseling, and 213 genetic counselors completed online
      surveys. No individuals identifying as transgender participated. The patient
      survey assessed disclosure of orientation, discrimination in genetic counseling,
      and quality of services received. The counselor survey assessed comfort with and
      attitudes about counseling GLBT patients, disclosure of counselor orientation,
      and whether they counsel differently with this population. Every patient denied
      experiencing discrimination during their session, but 17% reported their genetic
      counselor assumed they were heterosexual, and 45% indicated intake forms were not
      GLBT-inclusive. A majority of counselors (91%) reported having counseled GLBT
      patients and indicated they were comfortable doing so (86%), and 72% indicated no
      differences in their counseling approaches with GLBT patients. Few counselors
      (17%) received training in GLBT issues, and most (61%) desired such education.
      Additional findings and practice and research recommendations are presented.

PMID- 21861241
TI  - Quality-by-design case study: investigation of the role of poloxamer in immediate
      release tablets by experimental design and multivariate data analysis.
AB  - The role of poloxamer 188, water and binder addition rate, on retarding
      dissolution in immediate-release tablets of a model drug from BCS class II was
      investigated by means of multivariate data analysis (MVDA) combined with design
      of experiments (DOE). While the DOE analysis yielded important clues into the
      cause-and-effect relationship between the responses and design factors,
      multivariate data analysis of the 40+ variables provided additional information
      on slowdown in tablet dissolution. A steep dependence of both tablet dissolution
      and disintegration on the poloxamer and less so on other design variables was
      observed. Poloxamer was found to increase dissolution rates in granules as
      expected of surfactants in general but retard dissolution in tablets. The
      unexpected effect of poloxamer in tablets was accompanied by an increase in
      tablet-disintegration-time-mediated slowdown of tablet dissolution and by a
      surrogate binding effect of poloxamer at higher concentrations. It was
      additionally realized through MVDA that poloxamer in tablets either acts as a
      binder by itself or promotes binder action of the binder povidone resulting in
      increased intragranular cohesion. Additionally, poloxamer was found to mediate
      tablet dissolution on stability as well. In contrast to tablet dissolution at
      release (time zero), poloxamer appeared to increase tablet dissolution in a
      concentration-dependent manner on accelerated open-dish stability. Substituting
      polysorbate 80 as an alternate surfactant in place of poloxamer in the
      formulation was found to stabilize tablet dissolution.

PMID- 21861242
TI  - Performance of serum cystatin C versus serum creatinine as a marker of glomerular
      filtration rate as measured by inulin renal clearance.
AB  - INTRODUCTION: Serum cystatin C was recently proposed as an alternative marker of
      glomerular filtration rate (GFR), with a suggested better performance than
      creatinine. However, detailed studies are limited. We evaluated the performance
      of cystatin C as a GFR marker. METHODS: GFR was measured by inulin clearance in
      763 Japanese subjects. Factors other than GFR influencing serum cystatin C or
      serum creatinine were analyzed by multivariate analyses. RESULTS: After
      adjustment for GFR, the value of serum creatinine was 25.2% lower in females than
      males, and decreased by 5.2% for every 20 years of age. Serum cystatin C was 8.2%
      lower in females, and did not change significantly with aging. Creatinine but not
      cystatin C was significantly affected by body weight, height and body mass index
      after adjustment for GFR, gender and age. The correlation coefficient between GFR
      and 1/cystatin C was significantly higher than that of 1/creatinine in total
      subjects (0.866 and 0.810, respectively, p < 0.001). Unlike serum creatinine,
      serum cystatin C did not increase in association with the reduction of GFR in
      subjects with very low GFR. The regression line of 1/cystatin C against GFR
      showed a significantly negative intercept of about -8 ml/min/1.73 m(2).
      CONCLUSION: The performance of serum cystatin C was not good in the subjects with
      very low GFR. Non-renal elimination of cystatin C may contribute to the result.
      The correlation between reciprocal cystatin C and GFR suggested its superiority
      in predicting GFR compared to creatinine in subjects with normal and mildly
      reduced GFR.

PMID- 21861243
TI  - Expression of hedgehog pathway components is associated with bladder cancer
      progression and clinical outcome.
AB  - Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number
      of human tumors. But its effects on the progression and prognosis of bladder
      cancer remain poorly understood. The aim of this study was to investigate
      expression patterns of Hh pathway components in bladder cancer and to elucidate
      their prognostic values in this tumor. The expression of sonic hedgehog (Shh),
      its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118
      specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue
      was determined by immunohistochemistry. Statistical analyses were applied to test
      the relationship between the expression of these three proteins and
      clinicopathologic features and prognosis. Immunohistochemical staining results
      showed the localizations of Shh and Ptch1 proteins to be mainly located in the
      cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the
      nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1
      proteins was correlated with pathological stage (P = 0.006, 0.006 and 0.008,
      respectively), venous invasion (P = 0.01, 0.01 and 0.012, respectively) and lymph
      node metastasis (P = 0.009, 0.01 and 0.013, respectively), but not with other
      factors including age, gender, tumor grade and recurrence of superficial cancer.
      Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins
      respectively showed poorer disease-free (P = 0.002, 0.002 and 0.001,
      respectively) and overall survival (all P < 0.001) than those with negative
      expression of these three proteins. Univariate and multivariate analysis of
      prognostic factors in bladder cancer patients indicated that the expression
      patterns of Shh, Ptch1 and Gli1 proteins were independent unfavorable prognostic
      factors (all P < 0.001). This is the first report describing about the
      correlation between Hh pathway and the prognosis of bladder cancer. Expression of
      Shh, Ptch1 and Gli1 proteins was greater in bladder cancers than in the adjacent
      normal tissues. The examination of their expression is potentially valuable in
      prognostic evaluation of bladder cancer.

PMID- 21861244
TI  - Achievement and maintenance of the new impact factor 2010.

PMID- 21861246
TI  - Molecular profiling for genetic variability in Capsicum species based on ISSR and
      RAPD markers.
AB  - The taxonomic identity of Capsicum species is found to be difficult as it
      displays variations at morpho-chemical characters. Twenty-two accessions of six
      Capsicum species, namely, C. annuum, C. baccatum, C. chinense, C. eximium, C.
      frutescens, and C. luteum were investigated for phenotypic diversity based on
      flower color and for genetic differences by molecular makers. The genetic cluster
      analyses of 27 RAPD and eight ISSR primers, respectively, revealed genetic
      similarities in the ranges of 23-88% and 11-96%. Principal component analysis of
      the pooled RAPD and ISSR data further supports the genetic similarity and
      groupings. Different species showed variations in relation to corolla shade of
      flower. C. annuum accessions formed a single cluster in the molecular analysis as
      maintaining their flower characteristic. C. chinense accession shared flower
      features with the accessions of C. frutescens and were found to be closer at
      genotypic level. C. luteum was found to be rather closer to C. baccatum complex,
      both phenotypically and genetically. The only accession of C. eximium presenting
      purple flowers falls apart from the groupings. The floral characteristics and the
      molecular markers are found to be useful toward the delineation of the species
      specificity in Capsicum collection and identification of genetic stock.

PMID- 21861245
TI  - Erectile dysfunction can improve the effectiveness of the current guidelines for
      the screening for asymptomatic coronary artery disease in diabetes.
AB  - About 40% of diabetic patients with asymptomatic coronary artery disease (CAD)
      are missed on the basis of the current screening guidelines. Erectile Dysfunction
      (ED) is a powerful marker of asymptomatic CAD. Aim of the study is to evaluate
      whether ED can improve the effectiveness of the current guidelines for the
      screening of CAD in diabetes. From among 299 consecutive men with newly diagnosed
      type 2 diabetes without any apparent vascular complication, 293 (mean age 56.6+/
      5.9 years) were enrolled. Among them, 219 did not have myocardial ischemia (NO
      CAD group) and 74 men had a coronary stenosis angiographically proven (CAD
      group). Five risk factors (RFs) of the current screening guidelines
      (hypertension, dyslipidemia, family history for CAD, smoking e
      micro/macroalbuminuria) and ED were assessed. ED was significantly more prevalent
      in the CAD than in the NO CAD group (37.8 versus 15.1%; P<0.001) and was a
      predictor of asymptomatic CAD (OR: 4.4; 95%CI: 2.1-9.0; P<0.001). If ED is added
      to the list of RFs, it can increase the sensitivity of the current guidelines
      from 62 to 89%, without a significant variation in specificity (from 60 to 57%).
      The negative predictive value can increase from 82 to 94%. ED can reduce from
      37.84 to 10.81% the percentage of patients with silent CAD missed at the
      screening. This study first shows that ED can improve the effectiveness in
      discriminating diabetic men to screen for asymptomatic CAD, when it is added to
      the list of RFs of the current screening guidelines.

PMID- 21861247
TI  - The genetic basis of craniofacial and dental abnormalities.
AB  - The embryonic head development, including the formation of dental structures, is
      a complex and delicate process guided by specific genetic programs. Genetic
      changes and environmental factors can disturb the execution of these programs and
      result in abnormalities in orofacial and dental structures. Orofacial clefts and
      hypodontia/ oligodontia are examples of such abnormalities frequently seen in
      dental clinics. An insight into the mechanisms and genes involved in the
      formation of orofacial and dental structures has been gradually gained by genetic
      analysis of families and by the use of experimental vertebrate models such as the
      mouse and chick models. The development of novel clinical therapies for orofacial
      and dental pathological conditions depends very much on a detailed knowledge of
      the molecular and cellular processes that are involved in head formation.

PMID- 21861248
TI  - Prevalence of enamel fluorosis in 12-year-olds in two Swiss cantons.
AB  - The neighbouring cantons Basel-Stadt and Basel-Landschaft had introduced
      different fluoridation schemes for caries prevention: Basel-Stadt provided
      drinking water fluoridated at 0.8-1 ppm F since 1962, while Basel-Landschaft
      introduced fluoridated domestic salt (250 ppm F since 1983). Representative
      samples of 12-year-old schoolchildren (6th-graders) were studied to evaluate the
      prevalence of (I) dental fluorosis (FOP) using the Thylstrup-Fejerskov (TF)
      index, (II) non fluoride-associated enamel opacities (non-FOP), and (III)
      hypoplasia of the incisors. Standardised frontal colour photographs were taken
      and assessed by four examiners after projection. Of 373 schoolchildren studied in
      1999 in Basel-Stadt 119 (31.9%) showed fluoride-associated enamel opacities, i.
      e. 66 (17.7%) a very mild form (TF score 1), 47 (12.6%) a mild form (TF score 2),
      five scored TF3 and one TF5. In addition, non-FOP were diagnosed in 115 (30.8%)
      and hypoplasia in 47 (12.6%) children. Among the 448 children evaluated in 2001
      in Basel-Landschaft 143 (31.9%) showed FOP, namely 74 (16.5%) scored TF1, 54
      (12.2%) scored TF2, 12 (2.7%) scored TF3, and three (0.7%) scored TF5. Non-FOP
      were found among 93 (20.8%) and hypoplasia among 56 (12.5%) children. Thus, in
      spite of different fluoridation schemes in the two cantons, the prevalences of
      FOP were identical. Most fluoride-associated enamel opacities were mild or very
      mild. They did not represent an aesthetic problem and certainly not a public
      health concern.

PMID- 21861249
TI  - [Zirconia in removable prosthodontics. A case report].
AB  - Zirconia as a framework material is well established in fixed prosthodontics.
      However, for its application for removable dentures little experience exists.
      Zirkonzahn(r) has developed a copy-milling unit, that is a manually operated
      machine for the manufacture not only of frameworks but also of complete removable
      dentures. The aim of this case report is to show the step-by-step clinical and
      technical fabrication of a zirconia bar on implants and of a corresponding
      zirconia complete denture. The advantages and disadvantages of the system are
      presented and problems are critically discussed.

PMID- 21861250
TI  - [How up-to-date are metal-based resin-bonded fixed partial dentures in the era of
      full-ceramics and dental implants? A case report].
AB  - Regardless of the success of preventive measures the replace!ment of missing
      teeth in young patients with caries-free dentitions is a daily challenge for the
      clinician. The decision-making process concerning the different treatment options
      is difficult, based on several equivalent solutions. Thereby the significance of
      minimal invasive approaches is steadily increasing. In indicated cases, resin
      bonded fixed partial dentures which were introduced in the last century still
      represent a well documented and minimally invasive procedure, even in the era of
      dental implants. In this article, clinical aspects of a conventional, metal-based
      resin-bonded fixed partial dentures are discussed according to the current
      literature and the clinical steps are presented in a clinical case.

PMID- 21861251
TI  - Medication safety in neonates.
AB  - Newborn intensive care units (NICUs) are high-risk areas of care, where complex
      medical interventions are performed, and are recognized as a resource for
      improved outcome in premature and low-birth-weight infants or those presenting
      with acute conditions. This critical environment, along with the vulnerable
      nature of the population it serves, places patients at risk for medication
      errors, which can result in permanent harm or death. Promoting safe medication
      practices requires participation of all individuals involved in the medication
      use process (e.g., physicians, nurses, nurse practitioners, physician assistants,
      pharmacists, respiratory therapists, pharmacy technicians). The following
      recommendations, organized in accordance with the Institute for Safe Medication
      Practices' Key Elements of the Medication Use SystemTM, will focus on significant
      areas of concern within the NICU. All individuals caring for neonates, supported
      by administrators and organizational leaders, should recognize themselves as
      active partners responsible for the safety of this fragile patient population by
      participating in the design and sustainment of a safe and efficient medication
      use system.

PMID- 21861252
TI  - Scheduled deliveries: avoiding iatrogenic prematurity.
AB  - The balance of maternal, fetal, and neonatal risks of continued pregnancy versus
      iatrogenic delivery must be based on best evidence. Although avoiding elective
      deliveries prior to 39 weeks is well established to improve neonatal outcomes,
      several "soft" conditions are commonly considered to require delivery prior to 39
      weeks. Review of existing literature suggests that with some of these conditions,
      delivery can be safely delayed until later in pregnancy or even allowed to
      proceed without intervention. Late preterm and early term deliveries contribute
      substantially to neonatal morbidity and health care costs and should be
      considered only if the risks of continuing the pregnancy exceed the neonatal
      risks related to early birth. In this article, we review some the common clinical
      scenarios that may result in scheduled early term or late preterm births, with a
      focus on practice strategies for improving maternal and neonatal outcomes.

PMID- 21861253
TI  - Surgical aspects of donor hand recovery for transplantation.
AB  - The purpose of this article is to share our institution's experience in
      optimizing the suitability of composite donor tissue for use in hand
      transplantation. The centerpiece of this process includes procurement techniques,
      preservation and timing issues, and anatomical matching. Recovery of the donor
      hand must proceed in an efficient, organized, and expedient manner. Proper timing
      of the donor operation not only ensures the quality of donor tissue and outcome
      for the hand recipient, but also allows surgeons recovering other organs to
      obtain high quality tissue for those recipients. Timing remains a critical factor
      in preserving tissue after removal from the donor. We will also consider the
      factors of temperature and preservation solution during transport.

PMID- 21861254
TI  - [What do patients with chronic obstructive pulmonary disease die from?].

PMID- 21861255
TI  - [An attempt to estimate potentially useful parameters to evaluate the normal
      range of nasal peak inspiratory flow].
AB  - INTRODUCTION: Measurement of peak nasal inspiratory flow (PNIF, peak nasal
      inspiratory flow) seems to be a cheap and simple method to assess nasal patency.
      Unfortunately, due to the lack of reference values a single measurement does not
      take any information about the degree of nasal obstruction. Therefore, the
      purpose of this study was to establish parameters useful for estimating PNIF
      reference values. MATERIAL AND METHODS: 221 respondents, from Wroclaw, answered a
      questionnaire based on ECRHS II and ISAAC. Sample was randomized based on the
      personal number, stratified and representative of age and sex. Subjects were
      divided into three groups on the basis of their age (6-7, 13-14 and 20-45 years).
      The PNIF was measured using an In-Check portable nasal inspiratory flow meter (In
      Check's Clement-Clark). The highest of the five PNIF values was used as the
      measure of PNIF for each subject in subsequent analyses (PNIF MAX). Patients with
      rhinitis and/or asthma were withdrawn from the study. RESULTS: Repeated
      measurements of PNIF were performed in 221 healthy volunteers. PNIF values were
      higher in males compared to women and this difference was statistically
      significant. There was a statistically significant correlation between height and
      PNIF MAX, and there was no such correlation between age and PNIF MAX. Stepwise
      linear regression that included gender, height, age revealed that only sex and
      height were independent significant predictors of PNIF. Obtained dependence PNIF
      MAX = -137.7 - 22.5 x + 1.7 y, where x is the sex (a woman, 0 - male) and the y -
      height. Coefficient of determination (R(2)) was 0.45 which means that regression
      equation explains about 45% of the observed PNIF MAX variability. CONCLUSIONS: A
      correlation was found between PNIF value and sex and height of the patients,
      while age is irrelevant in this regard. Difficulty of establishing standards for
      the PNIF parameter are probably due to anatomical differences in the construction
      of the nose.

PMID- 21861256
TI  - [Outcome of three-dimensional conformal radiotherapy for early stage non-small
      cell lung cancer patients who met or not inclusion criteria for stereotactic-body
      radiation therapy].
AB  - INTRODUCTION: In early stage non-small cell lung cancer (NSCLC) the stereotactic
      body radiation therapy (SBRT) gives promising results, similar to the results of
      surgical series. However, not all such patients are the candidates for this
      treatment method. The retrospective analysis of the results of three-dimensional
      conformal radiotherapy (3D-CRT) in stage I and II of NSCLC was undertaken, with a
      special focus on the patients who were candidates for SBRT treatment, but
      received 3D-CRT due to no access to the SBRT. MATERIAL AND METHODS: One hundred
      thirty-two consecutive stage I-II NSCLC patients who received radical 3D-CRT
      between 1998 and 2009 were included. Different radiotherapy schedules were used;
      thus the biologically equivalent doses (BED) were calculated for all. Sixty-eight
      patients met criteria of qualification for SBRT (peripheral T1-3N0 tumors with
      diameter L 5 cm). Overall survival and local progression free survival (LPFS)
      were estimated for the whole group and compared for patients being and not being
      candidates for SBRT. Uni- and multivariate analyses were performed for prognostic
      factors. RESULTS: Median BED value was 74 Gy (58-82 Gy). Patients who met SBRT
      criteria had significantly smaller gross tumor volume (GTV) comparing to the
      remainder (p < 0.00001). Three-year overall and local progression free survival
      rates were 37% and 50%, respectively. In comparison of SBRT candidates and
      others, only significant difference in three-year LPFS was obtained, 58% and 35%,
      respectively, p = 0.04. However, in the multivariate analysis, GTV, performance
      status, and stage were the only three prognostic factors for LPFS. CONCLUSIONS:
      After 3D-CRT, superior local control for early stage NSCLC patients who met
      criteria of inclusion for SBRT in comparison with the remainder was demonstrated.
      However, this outcome was inferior to the local control after SBRT reported in
      the literature.

PMID- 21861257
TI  - [Costs of chronic obstructive pulmonary disease in patients treated in ambulatory
      care in Poland].
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      death worldwide. A cost-of-illness study aims to determine the total economic
      impact of a disease or health condition on society through the identification,
      measurement, and valuation of all direct and indirect costs. Exacerbations are
      believed to be a major cost driver in COPD. The aim of this study was to examine
      direct, mean costs of COPD in Poland under usual clinical practice form societal
      perspective. MATERIAL AND METHODS: It was an observational bottom-up-cost-of
      illness study, based on a retrospective sample of patients presenting with COPD
      in pulmonary ambulatory care facilities in Poland. Total medical resources
      consumption of a sample were collected in 2007/2008 year by physician - lung
      specialists. Direct costs of COPD were evaluated based on data from different
      populations of five clinical hospitals and eight out-patient clinics. Resources
      utilisation and cost data are summarised as mean values per patient per year. 95%
      confidence intervals were derived using percentile bootstrapping. RESULTS: Total
      medicals resources consumption of a COPD patient per year was 1007 EURO (EUR 1 =
      PLN 4.0; year 2008). Among this cost 606 EURO was directly related to COPD follow
      up, 105 EURO was related to ambulatory exacerbation, and 296 EURO was related to
      exacerbation treated in hospital. CONCLUSIONS: The burden of COPD itself appeared
      to be considerable magnitude for society in Poland.

PMID- 21861258
TI  - [Mortality and comorbidity in hospitalized chronic obstructive pulmonary disease
      patients].
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a fourth cause of
      death in USA and is expected to be the third cause of death by year 2020. It is
      believed that some diseases like cardiovascular diseases, osteoporosis, cachexia,
      anaemia are systemic consequences of COPD. Some data show that the co-morbidities
      are more frequent in severe COPD patients than in control groups and are
      associated with the serious health outcomes. It is debated whether extra
      pulmonary comorbidities or pulmonary complications are the main reason of death
      in COPD. The aim of the study was to analyze the mortality and comorbidity in
      COPD patients who died during hospitalization in the Department of Pneumonology
      and Allergology in WMU from 2004 to 2008. MATERIAL AND METHODS: We analyzed 266
      records of patients who had diagnosis of COPD and died during hospitalization
      (179 [67%] M and 87 [33%] F). The mean age at death was 73 +/- 8 years (M 73 +/-
      8 years, F 74 +/- 9 years). RESULTS: The most frequent cause of death were: COPD
      exacerbation (n = 81 [30%], F = 32, M = 49), pneumonia (n = 67 [25%], F = 17, M =
      50), lung cancer (n = 50 [19%], F = 18, M = 32), ischemic heart disease (n = 20
      [7%], F = 5, M = 15), cardiovascular insufficiency (n = 14 [5%], F = 6, M = 8)
      and other (n = 34 [14%]). The lung cancer was more frequent cause of death in
      younger patients (p = 0.002), and pneumonia in older (p = 0.02). In COPD patients
      the following comorbidities were diagnosed: chronic heart failure (n = 169),
      hypertension (n = 103), ischaemic heart disease (n = 102), diabetes mellitus type
      2 (n = 55), renal insufficiency (n = 43), hypertrophy of prostate (n = 36),
      arteriosclerosis obliterans (n = 28), osteoporosis (n = 19), anaemia (n = 14) and
      others. CONCLUSIONS: 1. The most frequent reasons of death were related to
      respiratory system: COPD exacerbation, pneumonia and lung cancer. 2. The most
      frequent diseases coexisting with COPD were cardiovascular disease, respiratory
      insufficiency and diabetes mellitus.

PMID- 21861259
TI  - Catamenial pneumothorax, clinical manifestations--a multidisciplinary challenge.
AB  - INTRODUCTION: Pleural endometriosis is a rare condition. Spontaneous, recurring
      pneumothorax occurring during menstruation, referred to as catamenial
      pneumothorax, is associated with pleural endometriosis. A multidisciplinary
      approach is needed for a successful result. MATERIAL AND METHODS: During the last
      five years (2005-2010), we have treated six patients with menstruation related
      pneumothorax at Oslo University Hospital. The surgical treatment was performed by
      the thoracic surgery department but the medical follow-up was carried out by the
      gynecological and pulmonary medicine departments. RESULTS: We report three of the
      patients treated. All three patients were premenopausal, aged 19-36, and had
      recurring, menstruation related, spontaneous pneumothorax, predominantly on the
      right side. The condition was treated by various surgical approaches, including
      chest tube drainage, video assisted thoracic surgery, chemical pleurodeses and
      thoracotomy. CONCLUSION: Spontaneous, recurring pneumothorax in women with no
      previous history of endometriosis can be the first manifestation of pleural
      endometriosis. The disorder requires surgical intervention, but early diagnosis
      and postoperative hormonal therapy are just as important for a successful
      outcome.

PMID- 21861260
TI  - [Overlap syndrome--asthma and chronic obstructive pulmonary disease].
AB  - Asthma and chronic obstructive pulmonary disease (COPD) as separate diseases are
      considered for a long time. Now this concept needs to be re-evaluated because in
      many clinical situations both diseases may coexist, or one condition may evolve
      into the other. Especially in older patients with obstructive disease an
      overlapping diagnosis of asthma and COPD may be observed. Epidemiological data
      show that overlap syndrome is recognized by the coexistence of incompletely
      reversible airway obstruction and features of airway remodeling. The analysis of
      clinical symptoms indicates that the risk factors are the same in asthma and
      COPD, and a role of inflammatory process in the small airways may be a key point
      to understand the pathology of overlap syndrome. Studying these events may bring
      new insights into the treatment of obstructive diseases of the respiratory tract.

PMID- 21861261
TI  - [When does nicotine dependence begin?].
AB  - Tobacco use leads in short time to nicotine dependence. Mechanisms of this
      process remain still not quite understood, of importance is also a question: When
      does nicotine dependence begin? The present review reports commonly used
      definition of nicotine dependence (according to Diagnostic and Statistical Manual
      of Mental Disorders Fourth Edition and International Statistical Classification
      of Diseases and Health Related Problems Tenth Revision), as well as its limited
      value in detecting first symptoms of this process. The review presents also the
      concept, which links the beginning of dependence with diminished autonomy (i.e.,
      autonomy theory), results of studies supporting this concept, and
      neurophysiologic model of sensitization-homeostasis for nicotine dependence
      development. Further, despite phenomenon of sensitization has not been
      demonstrated in humans, results of animal studies arguing for sensitization
      homeostasis theory are presented in the article. Usefulness of the Hooked on
      Nicotine Checklist in diagnosing first nicotine dependence symptoms in
      adolescents is also pointed out.

PMID- 21861262
TI  - [Eosinophilic pneumonia in response to cutaneous larva migrans syndrome--a case
      report].
AB  - Cutaneous larva migrans is a parasitic dermatosis imported by travelers returning
      from tropical and subtropical regions. In cutaneous larva migrans syndrome humans
      are incidental hosts and the larvae are unable to complete their natural cycle.
      Adult hookworms live in the intestines of dogs and cats, shedding eggs in feces
      that hatch and mature into larvae that can remain infective for months in the
      soil. Larvae penetrate the skin after contact with infected soil and cause an
      itchy creeping eruption. Cutaneous larva migrans is not usually associated with
      systemic symptoms and is rarely accompanied by peripheral blood eosinophilia. We
      report a patient who had both cutaneous larva migrans syndrome caused by
      Ancylostoma brasiliense and eosinophilic pneumonia after returning from Sri
      Lanka. The patient has been applied intravenous corticosteroids and local
      treatment with albendazole ointment with a very good clinical response.

PMID- 21861263
TI  - [Primary immune thrombocytopenia in a patient with sarcoidosis].
AB  - Sarcoidosis is a disease with a strongly variable clinical manifestation. It may
      be associated with various autoimmune diseases but hematological manifestations
      have rarely been observed. The prevalence of thrombocytopenia in patients with
      sarcoidosis has been estimated at 2%, about 1% of patients with thrombocytopenia
      have been diagnosed with sarcoidosis We present a case of sarcoidosis associated
      with primary immune thrombocytopenia of an abrupt and severe onset. Three
      potential patomechanisms of thrombocytopenia in sarcoidosis: 1) autoantibody
      related platelet destruction, 2) bone marrow involvement, and 3) hipersplenism
      are discussed.

PMID- 21861264
TI  - Reproducibility of ultrasound measurement of the abdominal aorta.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) screening and surveillance programmes
      use ultrasound imaging to measure the anteroposterior (AP) diameter of the
      infrarenal aorta. The aim of this study was to examine potential observer bias
      and variability in ultrasound measurements. METHODS: Studies were identified for
      review via a MEDLINE database search (1966-2009). References supplied in accessed
      papers were also checked for potential relevance. Consistent search terminology,
      and inclusion and exclusion criteria were used to ensure quality of data. Nine
      papers were available to review. RESULTS: Variation in intraobserver
      repeatability and interobserver reproducibility was identified. Six studies
      reported intraobserver repeatability coefficients for AP aortic diameter
      measurements of 1.6-4.4 mm. These were below the 5-mm level regarded as
      acceptable by the UK and USA AAA screening programmes. Five studies had
      interobserver reproducibility below the level of 5 mm. Four studies, however,
      reported poor reproducibility (range from -2 to +5.2 to -10.5 to +10.4); these
      differences may have had a significant clinical impact on screening and
      surveillance. CONCLUSION: The studies used different methodologies with no
      standardized measurement techniques. Measurements were taken by observers from
      different medical disciplines of varying grade and levels of training. Standard
      training and formal quality assurance of ultrasound measurements are important
      components of an effective AAA screening programme.

PMID- 21861266
TI  - Role of axillary clearance for patients with sentinel node-positive early breast
      cancer.

PMID- 21861265
TI  - Was the drop in mammography rates in 2005 associated with the drop in hormone
      therapy use?
AB  - BACKGROUND: In 2005, mammography rates in the United States dropped nationally
      for the first time among age-eligible women. An increased risk of breast cancer
      related to hormone therapy (HT) use reported in 2002 led to a dramatic drop in
      its use by 2005. Because current users of HT also tend to have higher mammography
      rates, the authors examined whether concurrent drops in HT and mammography use
      were associated. METHODS: Multivariate logistic regression was used to test for
      an interaction between HT use and survey year, controlling for a range of
      measurable factors in data from the 2000 and 2005 National Health Interview
      Surveys (NHIS). RESULTS: Women ages 50 to 64 years were more likely to report a
      recent mammogram if they also reported more education, a usual source of care,
      private health insurance, any race except non-Hispanic Asian, talking with an
      obstetrician/gynecologist or other physician in the past 12 months, or were
      currently taking HT. Women aged >= 65 years were more likely to report a recent
      mammogram if they also reported younger age (ages 65-74 years), more education, a
      usual source of care, having Medicare Part B or other supplemental Medicare
      insurance, excellent health, any race except non-Hispanic Asian, talking with an
      obstetrician/gynecologist or other physician in the past 12 months, or were
      currently taking HT. CONCLUSIONS: The change in HT use was associated with the
      drop in mammography use for women ages 50 to 64 years but not for women aged >=
      65 years. NHIS data explained 70% to 80% of the change in mammography use.

PMID- 21861267
TI  - Using MRI for the assessment of paraoxon-induced brain damage and efficacy of
      antidotal treatment.
AB  - Organophosphate intoxication induces neural toxicity as demonstrated in
      histological analysis of poisoned animals. Diffusion-weighted magnetic resonance
      imaging (DWMRI) enables early noninvasive characterization of biological tissues
      based on their water diffusion characteristics. Our objectives were to study the
      application of MRI for assessment of paraoxon-induced brain damage and the
      efficacy of antidotal treatments. Seventy-six rats were poisoned with paraoxon
      followed by treatment with atropine and obidoxime. The rats were then divided
      into five treatment groups consisting of midazolam after 1 or 30 min, scopolamine
      after 1 or 30 min and a no anticonvulsant treatment group. Five untreated rats
      served as controls. Animals underwent MRI on days 1, 8, 15, 29 and 50 post
      poisoning. Histological evaluation was performed on representative rat brains.
      Acute DWMRI effects, such as enhancement of temporal brain regions, and chronic
      effects such as ventricular enlargement and brain atrophy, depicted on T2
      weighted MRI, were significantly more prominent in late anticonvulsant treatment
      groups. There was no significant difference between the neuroprotective effects
      of midazolam and scopolamine as shown by DWMRI. Early MRI abnormalities were
      found to correlate significantly with histological analysis of samples obtained
      15 days post treatment. In conclusion, our results demonstrate the feasibility of
      using DWMRI for depiction of early cytotoxic response to paraoxon and T2-weighted
      MRI for later changes, thus enabling assessment of early/late brain damage as
      well as treatment efficacy in rats. The ability to depict these changes early and
      noninvasively may be applied clinically in the acute phase of organophosphate
      poisoning.

PMID- 21861268
TI  - S100B promotes the proliferation, migration and invasion of specific brain
      metastatic lung adenocarcinoma cell line.
AB  - Brain metastasis frequently occurs in cancer patients and is associated with a
      poor prognosis. We previously reported that S100B was highly expressed in PC14/B,
      a specific brain metastatic lung adenocarcinoma cell line, which suggests that it
      is associated with brain metastasis of lung cancer. However, the role of S100B in
      brain metastasis remains to be elucidated. In this study, using PC14/B cell line,
      we found that siRNA mediated depletion of S100B in PC14/B cells led to notable
      differences in cell proliferation, apoptosis, cell cycle progression, colony
      formation ability, cell migratory and invasive activity compared with the mock
      transfected cells. Therefore, our data suggest that S100B promotes the brain
      metastasis of lung adenocarcinoma by promoting cell proliferation, preventing
      apoptosis and increasing cell migration and invasion.

PMID- 21861269
TI  - Efficient organic solar cells with solution-processed silver nanowire electrodes.

PMID- 21861270
TI  - Two-dimensional nanocrystals produced by exfoliation of Ti3 AlC2.

PMID- 21861271
TI  - Radical polymer-wrapped SWNTs at a molecular level: high-rate redox mediation
      through a percolation network for a transparent charge-storage material.

PMID- 21861272
TI  - Behavioural activation for the treatment of low-income, African American
      adolescents with major depressive disorder: a case series.
AB  - Behavioural activation (BA) is a psychosocial treatment that has shown promise in
      the treatment of adults suffering from major depressive disorder (MDD). Recent
      studies have shown that BA may also be effective for treating depressed
      adolescents. There are no studies that have reported on the BA treatment of
      depressed and low-income African American adolescents; thus, the current study
      reports on the effectiveness of a version of BA adapted for the treatment of
      African American adolescents who were diagnosed with MDD (n = 3). Participants
      were allowed to attend a maximum of 17 sessions of weekly psychotherapy. Based on
      results taken from structured interviews, two of the three participants no longer
      met criteria for MDD at the end of treatment, and the severity of clinician-rated
      depressive symptoms and impairment decreased for all participants at post
      treatment assessment. Additionally, all participants and their caregivers
      reported satisfaction with treatment. Implications of these findings, study
      limitations and suggestions for future directions are discussed.

PMID- 21861273
TI  - Relevance of social and self-standards in eating disorders.
AB  - OBJECTIVE: To compare the importance given to self/other standards by eating
      disorder (ED) patients and healthy controls. METHODS: A total of 392 individuals
      (240 consecutively referred and 152 healthy controls) took part in this study.
      All subjects were diagnosed according to the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, Text Revision criteria and were female
      patients. Participants completed the Family Style, Self-Expectations and
      Emotional related subscales of the Cross-Cultural Questionnaire. RESULTS: Three
      domains (namely, family standards, self-achievement and physical appearance) were
      associated with ED. Family standards scores discriminated for the presence of an
      ED (area under receiver operating characteristic curve equals 0.89), the main
      predictors being a higher level of importance of physical appearance (p < .001),
      family standards (p = .029) and conflicts with parents about physical appearance
      (p < .001). Higher self-standards, in physical appearance, were more relevant in
      bulimia nervosa and ED not otherwise specified, whereas higher family standards
      were more associated with anorexia nervosa. CONCLUSIONS: High self-standards and
      social standards are common features in ED. The parallelism that ED may establish
      between reaching them and their life success may have a crucial role as a
      developing and maintaining factor in ED.

PMID- 21861275
TI  - Direct writing and actuation of three-dimensionally patterned hydrogel pads on
      micropillar supports.

PMID- 21861274
TI  - Sequential SPECT and optical imaging of experimental models of prostate cancer
      with a dual modality inhibitor of the prostate-specific membrane antigen.

PMID- 21861276
TI  - Enhanced performance and stability of a polymer solar cell by incorporation of
      vertically aligned, cross-linked fullerene nanorods.

PMID- 21861278
TI  - Rapid hepatic clearance of 99mTc-TMEOP: a new candidate for myocardial perfusion
      imaging.
AB  - BACKGROUND: (99m)Tc labeled radiotracers used in clinical practice lack the
      perfect characteristics for myocardial perfusion imaging. In particular, the high
      liver uptake can interfere in the interpretation of the inferior myocardial wall.
      Within the tricarbonyl approach, we used tris(pyrazolyl)methane (99m)Tc
      organometallic complexes as a lead structure. Herein we present the production,
      in vivo and in vitro metabolic studies in rats and the first in vivo
      biodistribution in rats for tri-methoxy-tris-pyrazolyl-(99m)Tc-(CO)(3) ((99m)Tc
      TMEOP), compared with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. METHODS: The
      chemical identity of (99m)Tc-TMEOP was characterized by RP-HPLC. The octanol
      water partition coefficient was determined under physiological conditions. In
      vitro stability and protein binding were determined using RP-HPLC. In vivo
      stability was determined in blood, heart, liver and kidney homogenates, intestine
      and urine using RP-HPLC. In vivo biodistribution was determined using dynamic
      planar acquisitions. Pinhole gated SPECT images were performed in other animals.
      Cardiac, liver and lung uptake were expressed as differential uptake ratios by
      drawing regions of interest in the organs of interest and around the total body.
      Heart-liver and heart-lung ratios were derived. Cardiac uptake was also expressed
      as percentage of injected activity. SPECT images were processed to determine the
      heart-liver ratio on SPECT images, to compare functional parameters between
      different tracers and to visualize homogeneous intracardiac tracer distribution.
      RESULTS: (99m)Tc-TMEOP is a moderately lipophilic cation, is stable and does not
      undergo any transformation in vitro. (99m)Tc-TMEOP also shows a high in vivo
      stability. In vivo imaging shows liver kinetics faster than those of (99m)Tc
      sestamibi and (99m)Tc-tetrofosmin. Cardiac uptake and functional analysis of
      pinhole gated SPECT data are comparable to those of (99m)Tc-sestamibi and (99m)Tc
      tetrofosmin. CONCLUSION: Although (99m)Tc-TMEOP shows a cardiac uptake between
      those of (99m)Tc-sestamibi and (99m)Tc-tetrofosmin, a better heart-liver ratio is
      obtained due to the faster liver washout. These results suggest possible faster
      cardiac perfusion imaging using (99m)Tc-TMEOP without liver activity
      interference.

PMID- 21861279
TI  - Surface functionalization of magnetic iron oxide nanoparticles for MRI
      applications - effect of anchoring group and ligand exchange protocol.
AB  - Hydrophobic magnetite nanoparticles synthesized from thermal decomposition of
      iron salts must be rendered hydrophilic for their application as MRI contrast
      agents. This process requires refunctionalizing the surface of the nanoparticles
      with a hydrophilic organic coating such as polyethylene glycol. Two parameters
      were found to influence the magnetic behavior and relaxivity of the resulting
      hydrophilic iron oxide nanoparticles: the functionality of the anchoring group
      and the protocol followed for the functionalization. Nanoparticles coated with
      PEGs via a catecholate-type anchoring moiety maintain the saturation
      magnetization and relaxivity of the hydrophobic magnetite precursor. Other
      anchoring functionalities, such as phosphonate, carboxylate and dopamine decrease
      the magnetization and relaxivity of the contrast agent. The protocol for
      functionalizing the nanoparticles also influences the magnetic behavior of the
      material. Nanoparticles refunctionalized according to a direct biphasic protocol
      exhibit higher relaxivity than those refunctionalized according to a two-step
      procedure which first involves stripping the nanoparticles. This research
      presents the first systematic study of both the binding moiety and the
      functionalization protocol on the relaxivity and magnetization of water-soluble
      coated iron oxide nanoparticles used as MRI contrast agents.

PMID- 21861280
TI  - An imageable retinoid acid derivative to detect human cancer xenografts and study
      therapeutic dosing to reduce its toxicity.
AB  - Developing agents with 'seek, treat and see' capability is critical for
      personalized molecular medicine. Those agents will specifically target the
      disease markers for diagnosis and apply the biologically effective dose for
      treatment. Retinoids regulate a multitude of biological processes. In addition,
      retinoic acid can reverse premalignancy, significantly decrease second primary
      tumors and provide a treatment benefit in head and neck, lung, esophagus, colon
      and bladder cancer. These data suggest that cancer cells can take up retinoids.
      Therefore, retinoids are potential tumor-imaging agents. We developed near
      infrared (NIR)-labeled retinoid agents to detect human cancers, visualize drug
      redistribution within the body, determine the optimal biological dose and reduce
      systemic toxicity. Our data demonstrate that the retinoid agent, but not the free
      dye, binds to the human tumor cells and is internalized, where it permits the
      imaging of human cancer xenografts. The high dose of retinoid agent is
      significantly associated with systemic toxicity. In summary, synthetic NIR
      labeled retinoid agents can be used to detect multiple human cancer xenografts as
      the agent is internalized by cancer cells. The binding of the agent to the tumor
      xenografts is dependent on the redistribution of the agent. Therapeutic agents
      labeled with reporters will interrogate tumor-drug interactions and permit
      analysis of biodistribution, pharmacokinetics and pharmacodynamics in real time.
      At the same time, we can apply the biologically effective dose for therapy,
      instead of the traditional maximum tolerated dose, to reduce systemic toxicity.

PMID- 21861281
TI  - Ultra-small gadolinium oxide nanoparticles to image brain cancer cells in vivo
      with MRI.
AB  - The majority of contrast agents used in magnetic resonance imaging (MRI) is based
      on the rare-earth element gadolinium. Gadolinium-based nanoparticles could find
      promising applications in pre-clinical diagnostic procedures of certain types of
      cancer, such as glioblastoma multiforme. This is one of the most malignant,
      lethal and poorly accessible forms of cancer. Recent advances in colloidal
      nanocrystal synthesis have led to the development of ultra-small crystals of
      gadolinium oxide (US-Gd(2)O(3), 2-3 nm diameter). As of today, this is the
      smallest and the densest of all Gd-containing nanoparticles. Cancer cells labeled
      with a sufficient quantity of this compound appear bright in T(1)-weighted MRI
      images. Here we demonstrate that US-Gd(2)O(3) can be used to label GL-261
      glioblastoma multiforme cells, followed by localization and visualization in vivo
      using MRI. Very high amounts of Gd are efficiently internalized and retained in
      cells, as confirmed with TEM and ICP-MS. Labeled cells were visualized in vivo at
      1.5 T using the chicken embryo model. This is one more step toward the
      development of "positively contrasted" cell tracking procedures with MRI.

PMID- 21861282
TI  - A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme
      activity.
AB  - The CEST effect of many PARACEST MRI contrast agents changes in response to a
      molecular biomarker. However, other molecular biomarkers or environmental factors
      can influence CEST, so that a change in CEST is not conclusive proof for
      detecting the biomarker. To overcome this problem, a second control CEST effect
      may be included in the same PARACEST agent, which is responsive to all factors
      that alter the first CEST effect except for the biomarker to be measured. To
      investigate this approach, a PARACEST MRI contrast agent was developed with one
      CEST effect that is responsive to esterase enzyme activity and a second control
      CEST effect. The ratio of the two CEST effects was independent of concentration
      and T(1) relaxation, so that this agent was self-calibrating with respect to
      these factors. This ratiometric method was dependent on temperature and was
      influenced by MR coalescence as the chemical exchange rates approached the
      chemical shifts of the exchangable protons as temperature was increased. The two
      CEST effects also showed evidence of having different pH dependencies, so that
      this agent was not self-calibrating with respect to pH. Therefore, a self
      calibrating PARACEST MRI contrast agent can more accurately detect a molecular
      biomarker such as esterase enzyme activity, as long as temperature and pH are
      within an acceptable physiological range and remain constant.

PMID- 21861283
TI  - Synthesis and characterization of new low-molecular-weight lysine-conjugated Gd
      DTPA contrast agents.
AB  - Various blood pool contrast agents (CAs), characterized by intravascular
      distribution, have been developed to assist contrast enhanced magnetic resonance
      angiography (MRA). Among these CAs, the DTPA derivatives conjugated to synthetic
      polypeptides, such as polylysine, represent attractive candidates for blood pool
      imaging. However, due to the presence of charged residues located on their
      backbone, these agents are retained in the kidneys and this compromises their
      long blood half-life. In order to overcome this major drawback of the polylysine
      compounds, two new low-molecular-weight CAs were synthesized in the present work
      by conjugating four or six 1-p-isothiocyanatobenzyl-DTPA moieties to tri- or
      penta-Lys peptides [(Gd-DTPA)(4) Lys(3) and (Gd-DTPA)(6) Lys(5)], respectively.
      All the -NH(2) groups of Lys were thus blocked by covalent conjugation to DTPA.
      The stability and relaxometric properties of these compounds, as well as their
      pharmacokinetic and biodistribution characteristics, were then evaluated. The
      half-life in blood of these new polylysine derivatives, as determined in rats, is
      twofold longer than that of Gd-DTPA. The compounds could thus be optimal blood
      pool markers for MRA, which typically uses fast acquisition times. The absence of
      positive molecular charge did not limit their retention in kidneys 2 h after
      administration. On the other hand, (Gd-DTPA)(4) Lys(3) is retained in kidneys to
      a lesser extent than (Gd-DTPA)(6) Lys(5) . Their moderate retention in blood and
      their higher stability and relaxivity in comparison with Gd-DTPA highlight these
      polylysine derivatives as optimal compared with previously developed polylysine
      compounds.

PMID- 21861284
TI  - In vitro biomedical applications of functionalized iron oxide nanoparticles,
      including those not related to magnetic properties.
AB  - Superparamagnetic iron oxide nanoparticles (SPION) are very promising contrast
      media, especially for molecular imaging, due to their superior NMR efficacy. They
      even have wider biomedical applications such as in drug and gene delivery, tissue
      engineering and bioseparation, or as sensitive biological nanosensors. By
      coupling them to affinity ligands, SPION can bind to drugs, proteins, enzymes,
      antibodies or nucleotides. For in vitro biomedical applications, the detection of
      molecular interaction is possible by using a diversity of systems capable of
      sensing the magnetic properties of these materials. The goal of the present work
      was to develop and validate various in vitro biomedical applications of
      ultrasmall superparamagnetic particles of iron oxide (USPIO), including some that
      are not related to their magnetic properties. USPIO coated with dextran, starch
      or bisphosphonate exposing carboxylate groups were synthesized and some of them
      were functionalized by conjugating various biomolecules, such as biotin,
      streptavidin and apoptosis, or VCAM-1 specific peptides. The in vitro biomedical
      applications assessed in the present work included: (1) the relaxometric
      measurement of antibody concentration, cell receptor expression, molecular
      interaction, and enzymatic activity in aqueous suspensions; (2) MRI visualization
      of cells and detection of molecular interaction in an ELISA system; (3) ELISA
      applications of USPIO derivatives; and (4) detection of specific biomolecules by
      histochemistry. Our results confirm that rapid and simple in vitro detection of a
      diversity of functionalized SPION with relevance in medicine is possible by the
      existing NMR techniques and by chemical staining reactions. The protocols can be
      applied to minimally prepared biological samples (e.g. whole blood, blood plasma
      or serum, cell suspensions, biopsies, histological preparations, etc.), and often
      do not need complicated systems of signal amplification. The use of SPION labeled
      compounds could furthermore contribute to cost reductions in the diagnosis and in
      patient care.

PMID- 21861286
TI  - 18F-FDG PET/CT and MRI in the follow-up of head and neck squamous cell carcinoma.
AB  - We evaluated the diagnostic performance of (18)F-FDG PET/CT and MRI for the
      assessment of head and neck squamous cell carcinoma (HNSCC) relapse. Since early
      treatment might prevent inoperable relapse, we also evaluated THE performance of
      early unenhanced (18)F-FDG PET/CT in residual tumor detection. The study was
      prospectively performed on 32 patients who underwent (18)F-FDG PET/CT and MRI
      before treatment and at 4 and 12 months after treatment. (18)F-FDG PET/CT was
      also performed 2 weeks after the end of radiotherapy. Histopathology or a minimum
      of 18 months follow-up were used as gold standard. Before treatment (18)F-FDG
      PET/CT and MRI detected all primary tumors except for two limited vocal fold
      lesions (sensitivity 94%). MRI was more sensitive than (18)F-FDG PET/CT for the
      detection of local extension sites (sensitivity 75 vs 58%), but at the cost of a
      higher rate of false positive results (positive predictive value 74 vs 86%). For
      relapse detection at 4 months, sensitivity was significantly higher for (18)F-FDG
      PET/CT (92%) than for MRI (70%), but the diagnostic performances were not
      significantly different at 12 months. For the detection of residual malignant
      tissue 2 weeks post-radiotherapy, sensitivity and specificity of (18)F-FDG PET/CT
      were respectively 86 and 85% (SUV cut-off value 5.8). (18)F-FDG PET/CT is
      effective in the differentiation between residual tumor and radiation-induced
      changes, as early as 2 weeks after treatment of a primary HNSCC. For follow-up,
      performance of (18)F-FDG PET/CT and MRI are similar except for a higher
      sensitivity of (18)F-FDG PET/CT at 4 months.

PMID- 21861285
TI  - Use of perfluorocarbon nanoparticles for non-invasive multimodal cell tracking of
      human pancreatic islets.
AB  - In vivo imaging of engraftment and immunorejection of transplanted islets is
      critical for further clinical development, with (1)H MR imaging of
      superparamagnetic iron oxide-labeled cells being the current premier modality.
      Using perfluorocarbon nanoparticles, we present here a strategy for non-invasive
      imaging of cells using other modalities. To this end, human cadaveric islets were
      labeled with rhodamine-perfluorooctylbromide (PFOB) nanoparticles, rhodamine
      perfluoropolyether (PFPE) nanoparticles or Feridex as control and tested in vitro
      for cell viability and c-peptide secretion for 1 week. (19)F MRI, computed
      tomography (CT) and ultrasound (US) imaging was performed on labeled cell
      phantoms and on cells following transplantation beneath the kidney capsule of
      mice and rabbits. PFOB and PFPE-labeling did not reduce human islet viability or
      glucose responsiveness as compared with unlabeled cells or SPIO-labeled cells.
      PFOB- and PFPE-labeled islets were effectively fluorinated for visualization by
      (19)F MRI. PFOB-labeled islets were acoustically reflective for detection by US
      imaging and became sufficiently brominated to become radiopaque allowing
      visualization with CT. Thus, perfluorocarbon nanoparticles are multimodal
      cellular contrast agents that may find applications in real-time targeted
      delivery and imaging of transplanted human islets or other cells in a clinically
      applicable manner using MRI, US or CT imaging.

PMID- 21861287
TI  - A fluorescent chromophore TOTO-3 as a 'smart probe' for the assessment of
      ultrasound-mediated local drug delivery in vivo.
AB  - Many potent anti-cancer drugs have an intracellular mode of action, but are
      limited in crossing the cell membrane, resulting in a reduced clinical efficacy.
      Ultrasound (US) is known to facilitate the penetration of drugs into tumors
      cells. However (molecular) imaging techniques that monitor in vivo the underlying
      processes of US-triggered drug delivery are lacking. The objective of this study
      was to demonstrate the feasibility of using a fluorescent nuclear acid stain
      (TOTO-3) as a model drug to monitor in real-time US-mediated delivery by in vivo
      fluorescence imaging. Following co-injection of TOTO-3 and microbubbles US was
      applied to the tumor. The time course of the drug delivery process was monitored
      by fluorescence imaging. Immunohistological analysis and in vitro experiments
      were performed to investigate the results in more detail. A significant signal
      intensity enhancement of the US-treated tumor was observed that indicates
      intracellular delivery of the dye. In the control tumor TOTO-3 signal was
      strongly associated with macrophages, which was not the case for the sonicated
      tumor. The capability of macrophages to uptake TOTO-3 was confirmed in vitro.
      This study demonstrates that an optical contrast agent with similar
      characteristics to an anti-cancer drug may be used for continuous in vivo
      monitoring of the drug delivery process.

PMID- 21861288
TI  - Assessment of melanoma extent and melanoma metastases invasion using electron
      paramagnetic resonance and bioluminescence imaging.
AB  - The clinical outcome of melanoma depends on the local and distant spread of the
      disease at the time of diagnosis, as the estimated 5-year survival rate is about
      100% for superficial melanoma diagnosed early, but less than 10% for melanoma
      that has disseminated to major organs such as lungs. There is a crucial need for
      new effective methods for the detection and the characterization of melanomas. In
      the pre-clinical setting, this will help to understand the factors that
      contribute to the malignancy while the transfer into the clinic will contribute
      to an early effective treatment of patients. Melanoma lesions can be detected by
      electron paramagnetic resonance (EPR) using paramagnetic properties of melanin
      pigments. As part of the development of EPR imaging to characterize melanomas, we
      evaluated in the present study the usefulness of EPR to report on the extension
      of lung metastases by comparing the method with bioluminescence imaging using B16
      melanoma cells expressing luciferase. B16 melanoma cells were injected
      subcutaneously or intravenously in C57/BL6 mice. The primary tumors or the lung
      colonization by melanoma cells was measured after several delay periods to obtain
      several degrees of invasiveness. The animals were measured in-vivo with
      bioluminescence after i.v. injection of luciferin. The primary tumors or lungs
      were then excised. After freeze-drying, the content of melanin in lungs was
      measured and imaged by EPR at 9 GHz. We observed a direct relationship between
      the EPR intensity and the bioluminescence intensity. Another tumor model (KHT
      sarcoma), non-pigmented but expressing luciferase, was used to confirm that the
      EPR signal was directly linked to the melanin pigment present in the tumors.

PMID- 21861289
TI  - Pharmacokinetics and magnetic resonance imaging of biodegradable macromolecular
      blood-pool contrast agent PG-Gd in non-human primates: a pilot study.
AB  - The purpose of this study was to evaluate poly(L-glutamic acid)-benzyl-DTPA-Gd
      (PG-Gd), a new biodegradable macromolecular magnetic resonance imaging contrast
      agent, for its pharmacokinetics and MRI enhancement in nonhuman primates. Studies
      were performed in rhesus monkeys at intravenous doses of 0.01, 0.02 and 0.08 mmol
      Gd/kg. T(1)-weighted MR images were acquired at 1.5 T using fast spoiled gradient
      recalled echo and fast spin echo imaging protocols. The small-molecule contrast
      agent Magnevist was used as a control. PG-Gd in the monkey showed a bi
      exponential disposition. The initial blood concentrations within 2 h of PG-Gd
      administration were much higher than those for Magnevist. The high blood
      concentration of PG-Gd was consistent with the MR imaging data, which showed
      prolonged circulation of PG-Gd in the blood pool. Enhancement of blood vessels
      and organs with a high blood perfusion (heart, liver, and kidney) was clearly
      visualized at 2 h after contrast injection at the three doses used. A greater
      than proportional increase of the area under the blood concentration-time curve
      was observed when the administered single dose was increased from 0.01 to 0.08
      mmol/kg. By 2 days after PG-Gd injection, the contrast agent was mostly cleared
      from all major organs, including kidney. The mean residence time was 15 h at the
      0.08 mmol/kg dose. A similar pharmacokinetic profile was observed in mice, with a
      mean residence time of 5.4 h and a volume of distribution at steady-state of 85.5
      ml/kg, indicating that the drug was mainly distributed in the blood compartment.
      Based on this pilot study, further investigations on the potential systemic
      toxicity of PG-Gd in both rodents and large animals are warranted before testing
      this agent in humans.

PMID- 21861290
TI  - Improved detection of pancreatic islets in vivo using double contrast.
AB  - The transplantation of pancreatic islets containing beta-cells, which produce
      insulin, is an alternative approach to the treatment of type 1 diabetes mellitus.
      The non-invasive visualization of transplanted islets can be performed using MRI;
      however, this requires labeling of the islets with a suitable contrast agent
      prior to transplantation. The detection of islets labeled by iron oxide-based
      contrast agents and transplanted into the liver tissue can be significantly
      improved using the intravenous administration of a suitable gadolinium contrast
      agent prior to MRI. The applied contrast agent not only improves the contrast-to
      noise ratio, but also eliminates artifacts that may lead to an overestimation of
      the number of hypointense spots and their area; thus it improves the accuracy of
      automated and semi-automated procedures used for transplanted islet segmentation
      and quantification.

PMID- 21861291
TI  - Labelling dendritic cells with SPIO has implications for their subsequent in vivo
      migration as assessed with cellular MRI.
AB  - An optimized non-invasive imaging modality capable of tracking and quantifying in
      vivo DC migration in patients would provide clinicians with valuable information
      regarding therapeutic DC-based vaccine outcomes. Superparamagnetic iron oxide
      (SPIO) nanoparticles were used to label bone marrow-derived DC. In vivo DC
      migration was tracked and quantified non-invasively using cellular magnetic
      resonance imaging (MRI) in a mouse model. Labelling DC with SPIO reflects the
      kinetics of DC migration in vivo but appears to reduce overall DC migration, in
      part due to nanoparticle size. Magnetic separation of SPIO-labelled (SPIO(+)) DC
      from unlabelled (SPIO(-)) DC prior to injection improves SPIO(+) DC migration to
      the lymph node. Corresponding MR image data better correlate with the presence of
      DC in vivo; an improved immunological response is also seen. Cellular MRI is a
      viable, non-invasive imaging tool that can routinely track DC migration in vivo.
      Consideration should be given to optimizing MRI contrast agent-labelling of
      clinical-grade DC in order to accurately correlate DC fate to immunological
      outcomes in patients.

PMID- 21861292
TI  - The application of ZnO luminescent nanoparticles in labeling mice.
AB  - Photoluminescent ZnO@polymer core-shell nanoparticles were used in mouse imaging
      through intradermal injections and intravenous injections, and the results proved
      that such ZnO fluorescence probes are nontoxic to live mice and have great
      potential in in vivo applications.

PMID- 21861293
TI  - Mitochondria-targeting single-walled carbon nanotubes for cancer photothermal
      therapy.
AB  - Nanomaterials have recently attracted much attention as efficient transducers for
      cancer photothermal therapy, based on their intrinsic absorption properties in
      the near-infrared region. This study explores a novel therapy model with
      mitochondria-targeting single-walled carbon nanotubes (SWNTs), which act
      efficiently to convert 980-nm laser energy into heat and selectively destroy the
      target mitochondria, thereby inducing mitochondrial depolarization, cytochrome c
      release, and caspase 3 activation. The laser+SWNTs process affords remarkable
      efficacy in suppressing tumor growth in a breast cancer model, and results in
      complete tumor regression in some cases. Laser+SWNTs could prove to be a
      promising selective local treatment modality, while minimizing adverse side
      effects.

PMID- 21861294
TI  - Exploring the formation of focal adhesions on patterned surfaces using super
      resolution imaging.
AB  - The formation of focal adhesions on various sizes of fibronectin patterns,
      ranging from 200 MUm to 250 nm, was systematically investigated by total internal
      reflection fluorescence microscopy and super-resolution imaging. It was found
      that cells adhered to and spread on these micro/nanopatterns, forming focal
      adhesions. On a micrometer scale the shape of the focal adhesions was elongated.
      However, on the nanometer scale, the shape of focal adhesions became dotlike. To
      further explore the distribution of focal adhesion proteins formed on surfaces, a
      localization-based super-resolution imaging technique was employed in order to
      determine the position and density of vinculin proteins. A characteristic
      distance of 50 nm was found between vinculin molecules in the focal adhesions,
      which did not depend on the size of the fibronectin nanopatterns. This distance
      was found to be crucial for the formation of focal adhesions. In addition, the
      density of vinculin at the focal adhesions formed on the nanopatterns increased
      as the pattern size decreased. The density of the protein was found to be 425 +/-
      247, 584 +/- 302, and 703 +/- 305 proteins MUm(-2)  on the 600, 400, and 250 nm
      fibronectin patterns respectively. Whereas 226 +/- 77 proteins MUm(-2)  was
      measured for the matured focal adhesions on homogeneous fibronectin coated
      substrates. The increase in vinculin density implies that an increase in
      mechanical load was applied to the focal adhesions formed on the smaller
      nanopatterns.

PMID- 21861295
TI  - N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery.
AB  - Small-interfering RNA (siRNA) is an emerging class of therapeutics, which works
      by regulating the expression of a specific gene involved in disease progression.
      Despite the promises, effective transport of siRNA with minimal side effects
      remains a challenge. In this study, a nonviral nanoparticle gene carrier is
      developed and its efficiency for siRNA delivery and transfection is validated at
      both in vitro and in vivo levels. Such a nanocarrier, abbreviated as Alkyl-PEI2k
      IO, was constructed with a core of iron oxide nanoparticles (IOs) and a shell of
      alkylated polyethyleneimine of 2000 Da [corrected] molecualr weight (Alkyl
      PEI2k). It is found to be able to bind with siRNA, resulting in well-dispersed
      nanoparticles with a controlled clustering structure and narrow size
      distribution. Electrophoresis studies show that the Alkyl-PEI2k-IOs could retard
      siRNA completely at N:P ratios (i.e., PEI nitrogen to nucleic acid phosphate)
      above 10, protect siRNA from enzymatic degradation in serum, and release
      complexed siRNA efficiently in the presence of polyanionic heparin. The knockdown
      efficiency of the siRNA-loaded nanocarriers is assessed with 4T1 cells stably
      expressing luciferase (fluc-4T1) and further, with a fluc-4T1 xenograft model.
      Significant down-regulation of luciferase is observed, and unlike high-molecular
      weight analogues, the Alkyl-PEI2k-coated IOs show good biocompatibility. In
      conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an
      innocuous toxic profile, making it a potential carrier for gene therapy.

PMID- 21861296
TI  - Bi(2) WO(6) inverse opals: facile fabrication and efficient visible-light-driven
      photocatalytic and photoelectrochemical water-splitting activity.

PMID- 21861297
TI  - Clinical feasibility of monitoring m-THPC mediated photodynamic therapy by means
      of fluorescence differential path-length spectroscopy.
AB  - The objective quantitative monitoring of light, oxygen, and photosensitizer is
      challenging in clinical photodynamic therapy settings. We have previously
      developed fluorescence differential path-length spectroscopy (FDPS), a technique
      that utilizes reflectance spectroscopy to monitor microvascular oxygen
      saturation, blood volume fraction, and vessel diameter, and fluorescence
      spectroscopy to monitor photosensitizer concentration. In this paper the clinical
      feasibility of the technique is tested on eight healthy volunteers and on three
      patients undergoing PDT of oral cavity cancers. Model-based analysis of the
      measured spectra provide quantitative tissue parameters that are corrected for
      background tissue absorption, autofluorescence, and the transmission of the
      optical system; this method allows comparison of intra- and inter-subject
      parameters. The FDPS correctly estimated the absence of m-THPC in volunteers and
      detected photobleaching in the areas receiving treatment light in patients
      undergoing PDT treatment. This study demonstrates the feasibility of monitoring
      clinical photodynamic therapy treatments using optical spectroscopy.

PMID- 21861298
TI  - The adolescent with menorrhagia: why, who, and how to evaluate for a bleeding
      disorder.

PMID- 21861299
TI  - Community-acquired methicillin-resistant staphylococcus aureus skin infection.

PMID- 21861300
TI  - ITS, OTUs and beyond-fungal hyperdiversity calls for supplementary solutions.

PMID- 21861301
TI  - Fungal defences against animal antagonists - lectins & more.

PMID- 21861302
TI  - Picture this... Tinea versicolor.

PMID- 21861303
TI  - Maternal mortality rates increase in the United States with risk of death 3 to 4
      times higher in African American women.

PMID- 21861304
TI  - Ensuring the inclusion of women from all races/ethnicities in research is
      everyone's responsibility.

PMID- 21861305
TI  - Reasons that women and providers miss or find opportunities to screen for type 2
      diabetes mellitus following gestational diabetes mellitus.

PMID- 21861306
TI  - [Combination therapy with macrolides for pneumonia].

PMID- 21861308
TI  - [Clinical efficacy of tebipenem pivoxil treatment in children with pneumonia, who
      had no relief despite having administered oral beta-lactam antibiotics].
AB  - We assessed the clinical efficacy of tebipenem pivoxil (TBPM-PI) in 30 children
      with pneumonia who, despite having received oral administration of beta-lactam
      antibiotics at the standard dose for at least 3 days, had no relief of symptoms
      and showed an abnormal shadow on the chest X-ray and elevated serum CRP levels of
      3.0 mg/dl or more between December 2009 and November 2010. TBPM-PI was
      administered at a single dose of 4 mg/kg twice a day for 3 days. The children
      ranged in age from 8 months to 5 years. The serum CRP level ranged from 3.05 to
      12.9 mg/dl. In 28 of the 30 children, either Streptococcus pneumoniae or
      Haemophilus influenzae or both were detected. Of the 28 children, 7 carried
      penicillin resistant S. pneumoniae; 9 carried beta-lactamase nonproducing
      ampicillin resistant H. influenzae; and 3 carried both. In all children,
      defervescence was observed within 48 hours of the start of TBPM-PI
      administration, and the severity of coughing/wheezing reduced significantly by
      the 3rd to 5th day. Thus, TBPM-PI was determined to be effective. Diarrhea or
      loose stool was observed as an adverse reaction in 4 children (13.3%).

PMID- 21861309
TI  - [Antibiotic therapy against acute tonsillopharyngitis in children due to group A
      beta-hemolytic streptococci: comparison of clinical efficacy, the bactericidal
      effects, and effects on oral flora between cefditoren pivoxil for 5 days and
      amoxicillin for 10 days].
AB  - We compared the clinical efficacy, the bactericidal effects, effect on the oral
      microbial flora, and adverse reactions between cefditoren pivoxil (CDTR-PI) for 5
      days and amoxicillin (AMPC) for 10 days in children with acute group A beta
      hemolytic streptococci (GAS) tonsillopharyngitis, and simultaneously examined the
      emm genotype and drug susceptibility of the isolated GAS. The results showed that
      the clinical efficacy was 100% for CDTR-PI and 97.9% for AMPC, with no difference
      between the two groups, and the bacterial elimination rate was 100% in both
      groups. No serious adverse event was noted in either group. On the other hand,
      concerning changes in the oral microbial flora between before and after
      treatment, the amount of bacteria showed no change in the CDTR-PI group (p =
      0.5761) but clearly decreased in the AMPC group (p = 0.0049). This indicates that
      CDTR-PI does not disturb the oral microbial flora compared with AMPC. Also, the
      emm types determined in the 112 GAS strains isolated in this study were similar
      to those that have recently been isolated frequently in Japan. Concerning the
      drug resistance, none of the isolates showed resistance to beta-lactam
      antibiotics, but 45% of them were resistant to macrolides. The advantages of
      short-term treatment are considered to include a lower cost, improvement in drug
      compliance, decrease in the frequency of the occurrence of adverse reactions,
      decrease in the frequency of the appearance of drug-resistant strains, and
      alleviation of the psychological burden of patients and their parents. For these
      reasons, we conclude that CDTR-PI for 5 days is a useful option for the treatment
      of acute GAS tonsillopharyngitis in children.

PMID- 21861307
TI  - [Bacteria isolated from surgical infections and its susceptibilities to
      antimicrobial agents--special references to bacteria isolated between April 2009
      and March 2010].
AB  - Bacteria isolated from surgical infections during the period from April 2009 to
      March 2010 were investigated in a multicenter study in Japan, and the following
      results were obtained. In this series, 671 strains including 16 strains of
      Candida spp. were isolated from 174 (79.1%) of 220 patients with surgical
      infections. Four hundred and eleven strains were isolated from primary
      infections, and 244 strains were isolated from surgical site infection. From
      primary infections, anaerobic Gram-negative bacteria were predominant, followed
      by aerobic Gram-negative bacteria, while from surgical site infection aerobic
      Gram-positive bacteria were predominant, followed by anaerobic Gram-negative
      bacteria. Among aerobic Gram-positive bacteria, the isolation rate of
      Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus
      spp. in this order, from primary infections, while Enterococcus spp. was highest,
      followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram
      negative bacteria, Escherichia coli was the most predominantly isolated from
      primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and
      Pseudomonas aeruginosa, in this order, and from surgical site infection, E. coli
      was most predominantly isolated, followed by P. aeruginosa and E. cloacae. Among
      anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the
      highest from primary infections, followed by Parvimonas micra, Streptococcus
      constellatus and Finegoldia magna, and from surgical site infection, E. lenta was
      most predominantly isolated. Among anaerobic Gram-negative bacteria, the
      isolation rate of Bilophila wadsworthia was the highest from primary infections,
      followed by Bacteroides fragilis, Bacteroides ovatus and Bacteroides
      thetaiotaomicron, and from surgical site infection, B. fragilis was most
      predominantly isolated, followed by B. ovatus, B. wadsworthia and B.
      thetaiotaomicron, in this order. In this series, we noticed no vancomycin
      resistant Gram-positive cocci, nor multidrug-resistant P. aeruginosa. We should
      carefully follow up B. wadsworthia which was resistant to various antibiotics,
      and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

PMID- 21861310
TI  - [Use of the critical path with the electronic chart system using meropenem,
      vancomycin, liposome amphotericin B for the febrile neutropenia].
AB  - Febrile neutropenia (FN) is a serious complication associated with morbidity and
      mortality. To manage infections in neutropenic patients, it is necessary to
      administer empirical antibiotic therapy in a timely and efficient manner. We
      developed an electronic critical pathway system for a computer-stored medical
      record system (EGMAIN-GX, Fujitsu), which matches FN patients to either: i) the
      first-line therapy with meropenem (3 g/day) alone, or ii) the second-line therapy
      with meropenem plus vancomycin (2 g/day). If patients do not respond to the first
      line therapy within 72 hours, then they are provided with the second-line
      therapy. A total of 28 FN events were treated in 14 patients presenting with
      hematological malignancies. The mean and median neutrophil counts were 42 (0
      300)/microl and 0/microl, respectively. The response rates with the first-line
      and second-line therapies were 57% and 93%, respectively. There were no serious
      adverse events. Meropenem is a highly effective treatment for FN. Use of an
      electronic critical pathway system could ensure that neutropenic patients receive
      this necessary empiric therapy in a timely manner so as to prevent the serious
      complications associated with FN.

PMID- 21861311
TI  - Hepatitis C of genotype 2: the role of medical invasive exams.
AB  - BACKGROUND AND AIM: Hepatitis C virus genotype 2 is the third in order of
      frequency in Belgium. The aim of this study was to better define the genotype 2
      carriers' epidemiology characteristics. METHODS: In a database comprising 1726
      viremic hepatitis C virus patient from the south part of Belgium, the files of 98
      genotype 2 carriers were reviewed. RESULTS: There was a strong association
      between genotype 2 and the mode of transmission. The rate of contamination by
      invasive medical exams was very high (23%), and statistically different from the
      one of the others genotypes. Eligibility for antiviral therapies and the rate of
      sustained viral response were high. CONCLUSION: HCV genotype 2 was highly
      associated with transmission by invasive medical exams.

PMID- 21861312
TI  - Are n-3 PUFA dietary recommendations met in in-hospital and school catering?
AB  - BACKGROUND: Literature provides compelling evidence for the health benefits of n
      3 polyunsaturated fatty acids (PUFA) consumption and low n-6/n-3 ratio, in
      particular, on inflammation and metabolic syndrome prevention and treatment.
      Consequently, recommendations were established for adequate n-3 PUFA supplies in
      the general population. The aim of our study was to evaluate the fatty acid (FA)
      profile in collective catering in relation to those recommendations. METHODS: We
      obtained composition of lunches provided by the Township of Lille (France) to
      children and adults, and of "standard", "low-fat" and "for diabetic" menus from
      the catering service of St Luc university hospital (Brussels, Belgium). The
      average proportions of fish, meat, oils, and dairy were used to estimate total,
      saturated, monounsaturated and polyunsaturated (n-6 and n-3) FA contents. We used
      official tables of foodstuffs composition provided by the French Agency for Food
      Safety, the project "Nutritional Composition of Aquatic Products", the French
      Institute for Nutrition, and the USDA National Nutrient Database for Standard
      Reference. French guidelines were taken as reference for daily recommended
      intakes. RESULTS: n-3 PUFA content in lunches provided by municipal catering and
      in in-hospital menus were slightly below recommended intakes. In the latter, n-3
      PUFA enriched margarine contributed for 50% to daily intakes. Despite, the n-6/n
      3 ratio was too high, especially in municipal catering (around 20), related to
      excessive n-6 PUFA supply. CONCLUSIONS: Our results highlight that meeting n-3
      PUFA nutritional recommendation remains challenging for collective catering. A
      detailed analysis of provided menus represents a powerful tool to increase
      awareness and foster improvement in practice.

PMID- 21861313
TI  - The influence of corticosterone on antizyme gene expression in early regenerating
      rat liver.
AB  - BACKGROUND AND STUDY AIMS: Antizyme 1, a specific inhibitor of Ornithine
      decarboxylase (ODC), plays a critical role in cell proliferation. Little is known
      about the impact of glucocorticoid on antizyme expression in the regenerating
      liver. In this paper, the effect of corticosterone on the gene expression of
      antizyme 1 in early regenerating rat liver induced by partial hepatectomy (PH)
      was investigated. MATERIALS AND METHODS: Bilateral adrenalectomies (ADX) were
      performed 3 days before PH. Corticosterone in sesame oil or sesame oil was
      injected sub-cutaneously to ADX rats. Antizyme 1 mRNA and protein levels as well
      as polyamine contents in the regenerating liver were determined by RT-PCR,
      Western blotting and HPLC, respectively. RESULTS: Antizyme 1 protein content in
      the oil-treated ADX group decreased significantly at 5, 7 and 9 h after PH
      compared to control. Following corticosterone administration the content rose
      dose-dependently during the whole experiment. At 5 h post-PH, the protein levels
      in 10 and 40 mg/kg corticosterone-treated ADX rats increased by 66% and 148%,
      respectively, when compared with the control group. However, no significant
      changes in antizyme 1 mRNA levels were observed in oil-treated ADX rats or
      corticosterone-treated groups compared to control. Polyamine contents in oil
      treated ADX rats were the highest among all groups at 5 and 9 h. Corticosterone
      treatment resulted in a dramatic decrease of polyamine contents at most of the
      time points investigated when compared with those in control rats. CONCLUSIONS:
      Corticosterone treatment induces antizyme 1 protein synthesis in early
      regenerating rat liver. However, it has little effect on antizyme 1 gene
      transcription. (Acta gastroenterol. belg., 2011, 74, 289-294).

PMID- 21861314
TI  - Development and psychometric evaluation of a dutch questionnaire for the
      assessment of anorectal and lower urinary tract symptoms.
AB  - BACKGROUND AND STUDY AIMS: Epidemiological studies have shown a frequent
      coexistence of symptoms and diseases affecting the anorectum and lower urinary
      tract. To further investigate combined symptoms and pathology of both pelvic
      viscera we developed a self-reported questionnaire, in Dutch, which extensively
      evaluates habits, complaints and symptoms of both viscera. We describe the
      construction and the psychometric properties of this questionnaire. PATIENTS AND
      METHODS: This prospective study was conducted in 56 patients with anorectal
      symptoms, 41 patients with lower urinary tract symptoms and in a control group of
      91 people. The following psychometric properties of the questionnaire were
      evaluated: content validity, construct validity, criterion validity, test-retest
      reliability and internal consistency. RESULTS: The questionnaire covered all
      important domains, was well interpreted and showed good acceptability (content
      validity). The questionnaire clearly differentiated the patient populations
      (construct validity). The criterion validity of the questionnaire was excellent.
      The test-retest reliability of the questionnaire was acceptable in all three the
      study populations (overall median kappa: 0.64; Inter Quartile Range: 0.56-0.75;
      mean agreement: 88%). The internal consistency of both anorectal and lower
      urinary tract symptom questions was high (Crohnbach's alpha of 0.78 and 0.80
      respectively). CONCLUSIONS: This questionnaire is a valid and reliable instrument
      for the assessment of anorectal and lower urinary tract symptoms. It can provide
      further insights into the epidemiology of concomitant bowel and bladder disorders
      and, accordingly, can contribute to a more efficient diagnostic and therapeutic
      approach in patients with such disorders.

PMID- 21861315
TI  - The use of colonoscopy to follow the inflammatory time course of TNBS colitis in
      rats.
AB  - BACKGROUND AND STUDY AIMS: Animal models of colitis are widely used to study the
      pathogenesis of inflammatory bowel diseases (IBD) and irritable bowel syndrome
      (IBS). However techniques allowing sequential assessment of colonic inflammation
      over time, without the need to sacrifice the animal, are required. This study
      evaluated in vive colonoscopy to follow the evolution of colitis in rats in
      comparison with the more commonly used post-mortem macroscopic, microscopic and
      biochemical assays of inflammation. METHODS: Colitis was induced in rats by a
      single intrarectal instillation of trinitrobenzene sulphonic acid (TNBS). Using a
      baby upper gastrointestinal endoscope, the severity of colitis was monitored at
      days 3, 10, 28 and 56 after the induction of colitis. Inflammation was scored by
      colonoscopy based on the degree of ulceration, extent of inflammation, mucosal
      bleeding, oedema and stenosis. During follow-up, rats were randomly selected for
      postmortem macroscopic and microscopic histology and myeloperoxidase (MPO)
      assessment of the colon. RESULTS: Colonoscopy showed signs of severe mucosal
      inflammation in the distal colon 3 days after induction of TNBS colitis.
      Subsequently, colitis subsided at days 10 and 28 with complete endoscopic
      remission at day 56. During the acute phase of inflammation, endoscopic findings
      were consistent with the post-mortem inflammatory parameters (macroscopic and
      microscopic histopathology, MPO colonic activity). A strong correlation between
      endoscopy and macroscopy remained even during the chronic phase of inflammation.
      CONCLUSIONS: Our findings suggest that routine endoscopy is a reliable method for
      monitoring the development and follow-up of the degree of TNBS colitis in rats.

PMID- 21861316
TI  - Buried bumper syndrome: low incidence and safe endoscopic management.
AB  - AIMS: Buried bumper syndrome (BBS) is a rare long-term complication of
      percutaneous endoscopic gastrostomy (PEG) and consists of a progressive impaction
      of the inner bumper of the tube in the mucosa of gastric wall. The aim of our
      study was to report our own experience with BBS, focusing on its incidence and
      endoscopic management. PATIENTS AND METHODS: Medical records of a large group of
      879 patients having undergone PEG insertion (2002-2009) were retrospectively
      reviewed. All PEG's were followed by our special Nutrition Support Team. Patients
      presenting with BBS during their follow-up were included in the study. RESULTS:
      Only eight patients (8/879; 0.9%) developed BBS, which was confirmed during
      gastroscopy. Median time between PEG insertion and BBS diagnosis was 22.0+/-22.28
      months. Five patients underwent successful treatment with: 1) flexible guide wire
      insertion through the internal orifice of the PEG to define its anatomical
      settings, 2) cruciform incisions of the gastric mucosa with a needle-knife
      starting at the center of the mucosal dome covering the internal bumper, and
      reaching its edges, 3) extrusion and complete extraction of the inner bumper
      through the gastric tract. No complications were observed. Median hospital stay
      related to BBS lasted 4.0+/-3.67 days. In two patients with peristomal abscess
      and deeply migrated bumper surgery was needed. CONCLUSIONS: Cruciform mucosal
      incisions with needle-knife is a safe endoscopic technique to treat the BBS that
      could avoid surgery in most of the cases. Preventive measures applied after PEG
      insertion and continued during the follow-up may result in a distinctly lower
      prevalence of BBS.

PMID- 21861317
TI  - IL28B polymorphism and the control of hepatitis C virus infection: ready for
      clinical use?
AB  - Polymorphisms in the region of the interleukin-28B (IL28B) gene have recently
      been associated with spontaneous and treatment induced clearance of hepatitis C
      virus infection. The specific mechanisms of how IL28B polymorphisms affect HCV
      suppression remain unknown. It is a matter of ongoing debate how to incorporate
      the IL28B data into the current treatment algorithms with pegylated interferon
      alpha and ribavirin. The eventual role of the IL28B genotype in new therapeutic
      regimes with direct antiviral agents needs to be explored in the ongoing and
      future clinical studies with these agents.

PMID- 21861318
TI  - Eosinophilic oesophagitis versus reflux oesophagitis.
AB  - Reflux oesophagitis (RO) is defined as the inflammation of the lower oesophagus
      due to damage caused by acid reflux from the stomach. Histopathologic features of
      acid reflux include epithelial hyperplasia, baloon cells, basal cell hyperplasia,
      papillary elongation, dilated intercellular spaces representing epithelial
      oedema, vascular congestion, and inflammatory cell infiltration comprising
      lymphocytes, neutrophils and eosinophils, most of which are nonspecific.
      Eosinophils, on the other hand, are considered to be important in the
      differential diagnosis of RO and EoO which is a chronic inflammatory disorder
      characterized by eosinophil infiltration of the oesophageal mucosa associated
      with a history of atopy or allergy. A cut off value of more than 15 eosinophils
      per high power field is suggestive of EoO with a tendency of eosinophils to
      concentrate in the superficial parts of squamous mucosa just below the luminal
      surface where they tend to form eosinophilic microabsesses. Dense fibrosis is
      seen in up to one-third of the patients with EoO together with an increase in the
      number of eosinophils in the lamina propria. In patients with intermediate levels
      of eosinophil counts (7-15 eos/hpf) immunohistochemistry for eosinophil secretory
      products could prove useful as it highlights degranulated eosinophils. In
      conclusion, distinguishing EoO from RO requires a thorough clinical, endoscopic
      and histologic evaluation of the patient which can only be achieved when close
      communication between pathologist and gastroenterologist is established.

PMID- 21861319
TI  - Endoplasmic reticulum stress and inflammatory bowel disease.
AB  - Endoplasmic reticulum (ER) stress arises from the accumulation of misfolded or
      unfolded proteins in the ER and elicits the unfolded protein response (UPR), an
      adaptive signalling pathway which aims at resolving ER stress. Genetic loci that
      confer risk for both forms of inflammatory bowel disease (IBD) include genes that
      are centrally involved in the UPR, including X-box binding protein-1 (XBP1),
      anterior gradient protein-2 (AGR2) and orosomucoid-1-like 3 (ORMDL3). The
      intestinal epithelium, in particular mucin-secreting goblet and antimicrobial
      peptide-secreting Paneth cells appear particularly sensitive towards disturbances
      of the UPR. Supportive of this view are mice with a genetic deletion of Xbp1
      specifically in the intestinal epithelium, which develop spontaneous intestinal
      inflammation histologically remarkably similar to human IBD. Apart from such
      primary genetic factors that determine the threshold of tolerable ER stress
      within the epithelium, secondary factors emanating from the environment might
      intersect with the UPR as well. These secondary factors might include microbial
      products, inflammatory mediators per se, hypoxia and glucose deprivation,
      pharmacological agents, and many others. Interaction of such secondary factors in
      a genetically susceptible host might provide the basis for intestinal
      inflammation and might provide a framework to investigate gene-environment
      interactions in human IBD, whereby a normally homeostatic adaptive response (i.e.
      the UPR) transforms into a potent pathomechanism of intestinal inflammation in
      the context of unresolved (i.e. unresolvable) ER stress.

PMID- 21861320
TI  - Splenic cystic lymphangioma in a young woman: case report and literature review.
AB  - Splenic cystic lymphangioma is extremely rare, with very few cases reported until
      now. Here, we report a case of cystic lymphangioma of the spleen in a young woman
      who was admitted for evaluation of abdominal pain and a mass lasting for two
      years. We present this case with emphasis on the problem of differential
      diagnosis and the difficulties of diagnostic certainty in the absence of
      histologic features.

PMID- 21861321
TI  - Primary duodenal follicular lymphoma: 6-years complete remission after combined
      radio-immunotherapy.
AB  - Primary gastrointestinal lymphoma (PGL) is known to account for 40% of all
      extranodal non-Hodgkin's lymphomas (NHLs) and between 4% to 12% of all NHLs. The
      small intestine is the site of presentation in 20-30% of cases, with the terminal
      ileum usually involved. Duodenal localizations have always been thought to be
      rare, but are presently growing in incidence. We herein report on a case of Stage
      IV primary duodenal FCL, located to the second portion of the duodenum with
      concomitant minimal bone marrow involvement. The patient was frontline approached
      with a conservative combined modality treatment consisting of 4 weekly infusions
      of the chimeric human-murine IgG1 mono-clonal antibody against the B-cell surface
      antigen CD-20, Rituximab (375 mg/m2) and consolidation 3D conformal external beam
      radiotherapy up to a total dose of 36 Gy given into 20 fractions to the involved
      duodenal portion. Six years after treatment has been completed, the patient is
      free from disease with no treatment-related toxicity.

PMID- 21861322
TI  - Lymphoepithelial cyst of the pancreas: case report and review of the literature.
AB  - BACKGROUND AND STUDY AIMS: Lymphoepithelial cyst of the pancreas (LCP) is a rare,
      benign cyst mimicking pseudocyst or cystic neoplasm. Literature describing LCP is
      limited to case or brief series reports, and the natural history of this
      condition is largely unknown. A literature review was carried out in order to
      elucidate the clinical, pathological and biochemical features of LCP. The aim of
      this study was to define diagnostic criteria and treatment. METHODS: A Medline
      and Pubmed search was conducted by using the key-words "lymphoepithelial cyst"
      and "pancreas". The articles found were accurately examined and all details
      regarding clinical and pathological features were included in a data-base.
      Furthermore, a case recently observed in our unit was added to the review.
      RESULTS: Ninety-two cases of LCP were found in the worldwide literature,
      including the case that we observed. LCP occurs more frequently in males
      (M:F=5.5:1), its preferred site is the tail of the pancreas, and its size ranges
      between 2 and 10centimetres. Histologically, it is a true cyst delineated by a
      keratinizing squamous epithelium surrounded by lymphoid tissue. LCP is
      asymptomatic in the majority of cases and preoperative diagnosis is complicated
      by a lack of specific radiological features of the disease. An accurate
      preoperative diagnosis can only be made by obtaining cytological specimens and
      placing them in the hands of a pathologist who is familiar with the cytological
      appearances of the disease. CONCLUSIONS: LCP is a rare lesion worldwide, without
      any prevalence in different countries or in different ethnic groups.
      Understanding the features of LCP, making an accurate diagnosis and
      differentiating it from cystic neoplasm preoperatively is vital, as when it is
      diagnosed certainly, a conservative treatment is justified. Otherwise, radical
      surgery in the form of pancreatic resection is required to exclude the diagnosis
      of pancreatic cystic neoplasm.

PMID- 21861323
TI  - An unusual cause of upper gastrointestinal bleeding: duodenal GIST. A case report
      and literature review.
AB  - A duodenal GIST is an unusual cause of upper gastrointestinal bleeding. Duodenal
      GISTs are rare and constitute 5% of all GISTs. A significant percentage of
      duodenal GISTs are located in the third and fourth portion of the duodenum and
      may not be detected on routine upper endoscopy. Push enteroscopy is necessary to
      locate these lesions. It is extremely important to differentiate a duodenal GIST
      from other submucosal tumors like leiomyomas, leiomyosarcomas or leiomyoblastomas
      which may present in a similar manner, because the treatment and prognosis differ
      significantly. Appropriate histological and immunohistiochemical staining is
      required to confirm the diagnosis. Surgical resection is the treatment of choice
      and may involve limited resection or a pancreaticoduodenectomy. Adjuvant therapy
      with Imatinib has been shown to prolong survival in patients with GIST in
      general.

PMID- 21861324
TI  - A case of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) with
      multiple polyps arising in the cecum and appendix.
AB  - We present the case of a 32-year-old female with cecal and appendiceal polyps
      that were removed by laparoscopy-assisted surgery. She also had recurrent
      nosebleeds due to telangiectases in the nasal mucosa and arteriovenous
      malformations in the lung, all of which contributed to the diagnosis of
      hereditary hemorrhagic telangiectasia.

PMID- 21861325
TI  - Necrotizing acute pancreatitis following therapeutic plasmapheresis in HCV
      related cryoglobulinemia.
AB  - Mixed cryoglobulinemia and hepatitis C virus infection are strongly connected and
      the therapeutic approach is standardized according to the severity of the
      symptoms. We report the difficult management of 59 year old female HCV patient
      presenting cutaneous lesions and arthralgia due to mixed cryoglobulinemia. No
      therapy was able to achieve a complete remission and during the six years of
      active disease we observed several clinical recurrences. The intensive
      plasmapheresis regimen led to a complete remission of the symptoms but it was
      associated with severe complications. In this case report we describe an episode
      of acute necrotizing pancreatitis due to intravascular haemolysis following
      therapeutic plasmapheresis. To the best of our knowledge the association between
      plasmapheresis and acute pancreatitis has not been previously described.

PMID- 21861326
TI  - Toxic megacolon due to fulminant Clostridium Difficile colitis.

PMID- 21861327
TI  - Acute pancreatitis after severe opthalmic adenoviral infection.

PMID- 21861328
TI  - Post-cholecystectomy amputation neuroma mimicking common bile duct carcinoma.

PMID- 21861329
TI  - Endobronchial metastases from colorectal cancer.

PMID- 21861330
TI  - [Mechanism of alcohol consumption-mediated Th2-polarized immune response].
AB  - Alcohol consumption impairs Th1-mediated cellular immune responses and enhances
      serum IgE levels. It has been reported that the elevated IgE levels are
      associated with a Th2 polarization response, but the mechanisms for enhancing Th2
      polarization by the ethanol treatment remain to be elucidated. The aim of this
      review is to present and discuss the mechanism of Th2 polarization response by
      alcohol. IL-12 production by APCs such as monocytes, macrophages, and dendritic
      cells (DCs) preferentially leads to Th1 polarization. Acute ethanol consumption
      results in a significant decrease in IL-12 production in LPS-stimulated DCs and a
      CD40/CD40L interaction between CD40 on the DCs and CD40 ligand expressed on
      activated T cells. This suggests that Th2 polarization by ethanol is caused by
      impaired IL-12 production from APCs. In contrast, the induction of IL-10 by LPS
      is enhanced by ethanol treatment, suggesting that elevated IL-10 may play a role
      in ethanol-induced suppression of IL-12. However, ethanol inhibited IL-12
      production in LPS-stimulated DCs devoid of IL-10 (IL-10/DC), suggesting that down
      regulation of IL-12 by ethanol is independent of the IL-10 levels. Furthermore,
      several studies report that PGE2, cAMP and linolic acid, and endogenous lipid
      mediators released in inflammatory conditions, also inhibit IL-12 production.
      These inhibitory effects are similar to the IL-12 inhibition by ethanol. In
      addition, increase in the levels of these lipid mediators is induced by ethanol
      treatment. Alternatively, cytokine signaling studies indicate that IL-12
      production by DCs is negatively regulated by PI3K and GSK-3, but positively
      regulated by p38 MAPK, mTOR, and NF-kappa B. Thus, it seems possible that ethanol
      may interact on the upstream of IL-12 producing a signal pathway. In fact,
      ethanol alters the stability of cell membrane, and suppresses clustering of TLR4
      and recruitment of signaling molecules into lipid rafts, where it associates with
      the Ser/Thr kinase and the adaptor proteins, and forms a signaling complex. Down
      regulation of lipid raft signaling is results in the impaired IL-12 production
      leading to the Th1 polarization, and causes CD4+ T cells to differentiation
      toward the Th2 lineage.

PMID- 21861331
TI  - [Functional homology between alcohol dependence and mood disorder].
AB  - Acute and chronic consumption of alcohol (ethanol) has been reported to modify a
      multitude of molecular events such as membrane fluidity, neurotransmitter
      turnover, function of neurotransmitter receptors and intracellular signal
      transduction systems coupling to neurotransmitter receptors, and biochemical
      processes in the central nervous system. Long-term consumption of alcohol
      produces alcohol dependence with comorbidity such as mood disorder, schizophrenic
      disorder and neurotic disorder. We examined functional changes in serotonin
      transporter (SERT) and serotonin receptors (5-HT(1A) and 5-HT(2A) receptors)
      related with depression using alcohol physical dependent mice and found
      correlated changes between depression and alcohol dependence. That is, SERT
      expression increased in the cingulate cortex, nucleus accumbens, hippocampal CA1
      CA3 layers, and mediodorsal nucleus of the thalamus. Moreover, 5-HT(1A) receptors
      in the cingulate cortex and hippocampus and 5-HT(2A) receptors in hippocampus
      decreased. In addition, increase of glucocorticoid with activation of the
      hypothalamus-pituitary-adrenal (HPA) axis is reported in both depression and
      alcohol dependence. These data suggest that similar changes of serotonin system
      and glucocorticoid response in brain may occur in both depression and alcohol
      dependence.

PMID- 21861332
TI  - [Effectiveness of drinking plan and drinking diary in intervention program (HAPPY
      program) for heavy drinkers].
AB  - We examined the effectiveness of a drinking plan (goal setting), and a drinking
      diary (self monitoring), in the intervention program (HAPPY program), for heavy
      drinkers in the workplace. 115 people participated, and 80 people were evaluated
      three months later and 31 people were evaluated one year later. We classified the
      drinking plans in the limitation of the quantity, non-drinking days, and the
      device of low risk drinking model. 75 people made the drinking diary for 12 weeks
      after brief intervention and studied three months later and 31 people were
      analyzed one year later. We evaluated on heavy drinking days of 28 days, and non
      drinking days of 28 days and standard drinks of 7 days. The limitation of the
      quantity model is effective for low risk drinking. The non-drinking day model is
      easily achieved, but not effective for low risk drinking. The device of low risk
      drinking model improved drinking habits for a long-term. The drinking diary for
      12 weeks after intervention improved drinking habits for a long-term. The
      drinking plan (goal setting), and drinking diary (self monitoring), in
      intervention program for heavy drinkers were effective for prevention of
      lifestyle-related disease and alcoholism.

PMID- 21861333
TI  - [Alcohol metabolism at moderate drinking in healthy men. Comparison between
      differences of alcohol beverages, with and without meal, and genetic
      polymorphism].
AB  - Studies on metabolisms of alcohol and the metabolites (e.g.:acetaldehyde) after
      drinking give basic and important information to recognize the physiological
      influence of drinking to human bodies. The aims of these studies were to clarify
      the influences of ALDH2 genotype difference, kinds of alcohol beverages, and
      fasted or prandial state to alcohol metabolisms at moderate drinking. The studies
      were conducted by a randomized cross-over design. After overnight fast, fifteen
      of ALDH2*1/*1 (Experiment 1) and twenty of ALDH21/*2 (Experiment 2) in Japanese
      healthy men aged 40 to 59 years old drank beer or shochu at a dose of 0.32g
      ethanol / kg body weight with or without test meal (460 kcal). The peak of blood
      ethanol (C(max)) was higher with shochu than with beer in the fasted condition in
      both ALDH2 genotypes, however, the difference between two types of alcohol
      beverages went out in the prandial condition. Simultaneous ingestion of test meal
      with alcohol beverage significantly decreased blood ethanol concentrations and
      increased ethanol disappearance rate (EDR) in the both genotypes. EDR values were
      significantly higher in ALDH2*1/*1 type than in ALDH2*1/*2 type in the both
      beverages with and without meal, whereas beta values showed no significant
      difference between two genotypes. The concentrations of blood acetaldehyde in
      ALDH2*1/*2 type were higher in prandial condition than in fasted condition with
      shochu. These results indicate that meal modified the differences of alcohol
      metabolism between beer and shochu and also between ALDH2 genotypes. Thus,
      alcohol metabolism in daily drinking is shown to be regulated by various
      combinatorial drinking conditions.

PMID- 21861334
TI  - [Evaluation of the Relapse Prevention Guidance for drug-dependent inmates: the
      intervention using self-teach workbook and group therapy in a "Private Finance
      Initiative" prison --the second report].
AB  - BACKGROUND: There has been no relapse prevention program for drug dependent
      inmates in Japanese prisons. Recently, "Relapse Prevention Guidance" program is
      provided to the adult male inmates in Harima Rehabilitation Program Center
      (HRPC), one of the newly founded "Private Finance Initiative" prisons. AIMS: To
      evaluate the effectiveness of the program by comparing the outcomes between
      groups of inmates with different severity level of dependence. METHODS: The
      program was provided to 89 subjects in HRPC. Inmates were classified into 4
      groups according to the severity measured by the Drug Abuse Screening Test
      (DAST). After a month of waiting period, self-teaching workbook was provided to
      each inmate for 4 weeks. The educational program consisting of 8 weekly
      psychoeducational group therapies was then provided to each group of 10 inmates.
      The evaluation was conducted both at the beginning and at the end of the workbook
      and the educational program intervention by administering 2 self-reporting
      questionnaires; the Self-efficacy Scale for drug dependence (SES), and the 8th
      version of the Stages of Change Readiness and Treatment Eagerness Scale for drug
      dependence (SOCRATES-8D). RESULTS: Only the "mild" group showed significant
      increase in SES during waiting period. After the workbook intervention,
      "moderate" group showed significant decrease in SES, and increase in the
      recognition and the ambivalence subscale of the SOCRATES-8D. The same increase in
      the subscales of SOCRATES-8D was noted in "Severe" group. Educational program
      produced increase in the recognition and the taking steps subscales of SOCRATES
      8D in "mild" group, increase in SES score and the taking steps subscale in
      "moderate", increase in SES score and total score of SOCRATES-8D in "severe"
      group. No significant change was noted in "very severe" group in any of the
      interventions. CONCLUSION: The "Relapse Prevention Guidance" is sufficiently
      effective, improving self-efficacy and motivation for change in drug dependent
      adult male inmates.

PMID- 21861335
TI  - [Evaluation of educational effects on drug dependence abstinence for convicts].
AB  - The object of this study is to evaluate the educational effects of group work
      sessions on drug dependence abstinence for convicts in Fukui Prison.
      Questionnaire surveys were conducted among participants on the first and last
      session. The results of surveys were analyzed quantitatively. The average ages of
      50 respondents were 39 years. 95.9% of them used methamphetamine among drugs and
      the majority has used drugs for the past 5 years. 93.9% of respondents had no
      medical treatment histories and 95.8% of them have not used any formal
      consultations. The survey result before the sessions showed that 75.5% of
      respondents showed positive stances towards participations on educational group
      work sessions. The survey after the sessions showed 67.4% of respondents were
      able to talk their drug problems in group meetings and 87.0% responded that group
      work sessions were helpful for solving drug problems. Also, 80.0% responded that
      they can stop using drugs and the percentage dropped by 11.0% from the first
      session. In terms of the participation in self-help groups after releases from
      the prison, the majority responded negatively, although 78.0% showed positive
      responses to using consultation services. The outcomes by means of evaluation
      scale also showed a significant improvement on denial and no relevant change on
      interpersonal trusts. This study revealed that it was possible to confirm the
      effectiveness of drug abstinence education through group work. It is important to
      consider three points in further studies; 1) cooperation between judicial and
      medical institutions for introducing consultation and medical treatments among
      convicts; 2) follow-up programs for reinforcing education on drug abstinence; 3)
      social welfare services in cooperation with educational effects to prevent
      repeated offences.

PMID- 21861336
TI  - [Endothelium-dependent vasorelaxation effects induced by apigenin on the thoracic
      aorta of rats and its possible mechanism].
AB  - OBJECTIVE: To investigate the vasorelaxant effect and mechanism of apigenin.
      METHODS: Rats were anesthetized with 1% sodium pentobarbital (i. p.) and killed
      by exsanguination. The thoracic aorta was isolated and cut into 3-4 mm rings and
      suspended in an organ bath filled with 20 ml Kreb solution which was maintained
      at 37 degrees C and ventilated continuously with 95% O2 and 5% CO2. The
      contraction was measured with a multichannel acquisition and analysis system (BIO
      PAC MP150, America). Related studies were conducted on the effect of apigenin on
      the contraction induced by phenylephrine (PE) and role of endothelium, K+ channel
      as well as Ca2+ channel in PE-induced relaxation. RESULT: Apigenin had no effect
      on the basal tension in rat aortic rings. Apigenin can relax PE pre-contracted
      rings in both endothelium-intact aortic and endothelium-denuded aortic in a dose
      dependent manner, with the effect of endothelium-intact aortic significantly
      stronger than that of endothelium-denuded aortic (P < 0.05). Pre-incubation of
      endothelium-intact rings with L-NAME and methylene blue significantly reduced
      apigenin-induced relaxation (P < 0.05). However, indomethacin did not
      significantly affect the apigenin-induced relaxation in endothelium-intact rings
      (P > 0.05). 4-AP, 5-HD, TEA as well as BaCl2 significantly inhibited apigenin
      induced relaxation in endothelium-denuded rings pre-contracted by PE (P < 0.05).
      In the K(+)-free solution, apigenin can significantly inhibit PE pre-contracted
      aortic rings (P < 0.05). In the Ca2(+)-free solution plus PE, cumulative addition
      of CaCl2 induced a stepwise tension increase of aortic rings. Pretreated with
      apigenin significantly attenuated CaCl2 induced contraction. CONCLUSION: Apigenin
      induces both endothelium-dependent and independent relaxation. NO and cGMP are
      involved in the endothelium-dependent relaxation, inhibition of voltage-dependent
      or receptor-operate Ca2+ channel or extracellular Ca2+ influx and activation of K
      channel contribute in part to the endothelium-independent relaxation by apigenin.

PMID- 21861337
TI  - [Oxidative stress and the susceptibility to obesity in rats].
AB  - OBJECTIVE: To evaluate the differences of oxidative stress level between obesity
      prone rats and obesity-resistant rats. METHODS: Male Wistar rats were divided
      into control group (10 rats) fed with basal diet and high fat group (30 rats) fed
      with high-fat diet for 6 weeks. Ten rats in obesity-prone (OP) group and obesity
      resistant (OR) group were selected from the high-fat diet group according to the
      gain of body weight. All rats were killed by the end of 13th week. Serum SOD,
      MDA, GSH-Px, blood lipids and fatty acids were detected by standard methods.
      RESULTS: SOD was lower in OP rats than that in OR rats and control rats. GSH-Px
      was lower in OP rats than that in OR rats. MDA was higher in OP rats than that in
      control rats. The energy intake, body fat content, FBG, serum lipids, serum
      insulin, ISI and free fatty acids in OP rats were significantly different from
      those in OR rats, but there were no differences between OR and control rats.
      CONCLUSION: Compared with OR rats, the oxidative stress responses were increased
      and the antioxidant capacities were decreased in OP rats after 13 weeks of
      experiment.

PMID- 21861338
TI  - [Anti-invasion effects of R- and S-enantiomers of equol on prostate cancer PC3,
      DU145 cells].
AB  - OBJECTIVE: To compare the effect of R- and S-enantiomers of equol on the motility
      and invasion in human prostate cancer cells PC3 and DU145. METHODS: Wound healing
      assay and transwell invasion assay were performed to assess the cell motility and
      invasion. Gelatin zymography and RT-PCR assay were performed to assess the
      related protein activity and mRNA expression. RESULT: R-(+) equol and S-(-)equol
      inhibited motility and invasion in PC3 and DU145 cells, separately. The results
      were more obvious in PC3 cells, and effect of R-(+) equol was stronger than its
      enantiomer S-(-) equol. MMP-2, MMP-9, the crucial members in metastasis, were
      found down-regulated by R-(+)equol and S-(-)equol. Subsequently, the estrogen
      receptor-alpha was activated by R-(+) equol, while no such effect on estrogen
      receptor-beta was observed. CONCLUSION: R-(+) equol and S-(-) equol inhibited
      motility and invasion in PC3 and DU145 cells, while the most strong effect was
      observed in PC3 cells by R-(+) equol, which might regulated by the activation of
      estrogen receptor-alpha.

PMID- 21861339
TI  - [Study on sub-chronic toxicity of powered milk containing transgenic human alpha
      lactalbumin].
AB  - OBJECTIVE: To investigate the potential toxic or adverse effect of transgenic
      human alpha-lactalbumin powered milk on rats. METHODS: Weanling Wistar rats were
      randomly divided into seven groups according the weight: three transgenic milk
      powder (T) groups, three non-transgenic milk powder (N) groups and the control
      (C) group. The diets of T groups contain 15%, 30% and 60% transgenic human alpha
      lactalbumin milk powder. The diets of N groups contain 15%, 30% and 60% non
      transgenic human alpha-lactalbumin milk powder for 90 days. The diet of C group
      contains only basic feed. Haematological and biochemical parameters was measured
      during the study (at 45th and 90th of the experiment). At the end of the 90th
      day, organ tissues analysis was performed. RESULTS: There were no transgenic
      human alpha-lactalbumin related adverse effects on the body weight, food intake,
      food consumption, hematology,serum biochemistry, as well as histopathology.
      CONCLUSION: There were no signs of toxic and adverse effects for transgenic human
      alpha-lactalbumin powdered milk on rats.

PMID- 21861340
TI  - [Boron background value survey of some foodstuffs in 12 provinces of China and
      boron primary intake estimation of Chinese habitants].
AB  - OBJECTIVE: To learn boron background value of some foodstuffs in China and
      estimation the primary intake of boron. METHODS: A total of 1035 grain, meat and
      fruit samples collected from 12 provinces in 2010 were analyzed for boron by ICP
      MS. The primary intake of boron was estimated by using the data of "Survey on the
      Status of Nutrition and Health of Chinese People" in 2002. RESULTS: Soybeans
      contain the highest concentration of boron among all the surveyed foodstuffs,
      with the background valued is 39.46 mg/kg. Fruit and pork contain second highest
      concentration of boron, with the background value range from 4 mg/kg to 7 mg/kg.
      Beef, mutton, rice and wheat flour contain less boron than other foodstuffs, with
      background value less than 4 mg/kg. The primary intake of boron for Chinese
      habitants is 1.62 mg per day and rice is the main source of dietary boron.
      CONCLUSION: Boron concentration varies in different foodstuffs and soybeans are
      rich in boron. The average intake of boron for Chinese habitants was among the
      safe range if no illegal boron added to food.

PMID- 21861341
TI  - [Mechanism of the effects of amitrole on the thyroglobulin in Fischer rat thyroid
      follicle-5 cell].
AB  - OBJECTIVE: The mechanisms of the effects of amitrole on the thyroglobulin (TG)
      was investigated in Fischer rat thyroid follicle-5 cell (FRTL-5 cells) and in the
      medium. METHODS: FRTL-5 cells were treated with 1, 10 and 100 microg/ml amitrole,
      and cytotoxicity was tested by 3H-TdR. The effects of amitrole on TG and thyroid
      transcription factor 1(TTF-1) in FRTL-5 cells were analyzed by RIA and ICC. And
      the TSHR in FRTL-5 cells was examined by Immunofluorescence analysis. RESULTS:
      1,10 and 100 microg/ml amitrole had no significant cytotoxicity to the FRTL-5
      cells (P > 0.05). The concentration of TG in the culture was decreased by 10 and
      100 microg/ml amitrole (P < 0.05), and the concentration of TG in the cells was
      decreased by 100 microg/ml (P < 0.05) but the TTF-1 in the cells were not
      obviously changed (P > 0.05). The TSHR in the surface of FRTL-5 cells was
      significantly decreased by all doses of amitrole (P < 0.01). CONCLUSION: The
      influence of amitrole on TG of FRTL-5 cells may be related to significantly
      reduce TSHR in the surface of FRTL-5 cells.

PMID- 21861342
TI  - [Effect of benzo [a] pyrene on HSP70 expression in rat cortical neurons in
      vitro].
AB  - OBJECTIVE: To explore the effect of benzo [a] pyrene (B [a] P) on heat shock
      protein 70 (HSP70) expression in rat cortical neurons in vitro. METHODS: SD rat
      cortical neurons were isolated and cultured, then they were exposed 24h with the
      doses of B [a] P (0, 0.1, 0.5, 1,5 and 10 micromol/L)and exposed 24h, 48h, 72h
      with doses of B [a] P (0, 0.5 and 5 micromol/L), observing dose-response
      relationship and time-dependent relationship, respectively. Including the 3%
      volume of S9 mixture was added in the medium. The neurons viability was detected
      by MTT assay. Western blot was used to measure the expression of HSP70 and
      immunofluorescence histochemistry was used to observe the expression and location
      of HSP70. RESULTS: When neurons were exposed 24h with B [a] P, compared with the
      control group, the expression of HSP70 was no significant difference in the group
      of 0.1 micromol/L dose of B [a] P (P > 0.05). The expression of HSP70 in groups
      from 0.5 to 10 micromol/L doses of B [a] P gradually decreased and was
      significantly reduced compared with 0.1 micromol/L group (P < 0.05). The
      difference between 10 micromol/L group and control group was significant (P <
      0.05). After neurons were exposed 24, 48 and 72h with B [a] P in groups of 0, 0.5
      and 5 micromol/L, HSP70 expression at different time-piont in 0.5, 5 micromol/L
      groups were significantly lower than the control group (P < 0.05). HSP70
      expression decreased with time extend in 0.5, 5 micromol/L groups and the
      difference between time points of 24h and 72h were significantly different (P <
      0.05). Immunohistochemistry showed that HSP70 expression was only in the
      cytoplasm in control group, but fluorescence expressed strongly and expressed in
      both cytoplasm and nuclear in 0.1 micromol/L group. As the dose increased, the
      expression of HSP70 in nucleus gradually increased and the fluorescence intensity
      gradually decreased. CONCLUSION: High doses of metabolites of B [ a] P (0.5 - 10
      micromol/L) inhibit the expression of HSP70 in cultured cortical neurons in rat,
      and there were relationships of dose and time-dependent between the dose and the
      inhibition. With the B [a] P dose increased HSP70 gradually moved to the nucleus.

PMID- 21861343
TI  - [Effects of acrylamide on rat neurobehavior, the contents of dopamine and its
      metabolites in nigrostriatal dopaminergic pathways].
AB  - OBJECTIVE: To explore the neurotoxic effect of acrylamide on nigrostriatal
      dopaminergic pathways in male SD rats and its mechanism. METHODS: Fourteen male
      SD rats were randomly divided into 2 groups: control group, and ACR exposed group
      (40 mg/kg). Exposed SD rats were intragastrically administrated acrylamide (40
      mg/kg) once daily for 12 days, the control rats were only administrated with
      normal saline by gavage. Neurobehavioral indexes including body weight, gait
      scores, nervous sensory to heat, foot splay in hindlimb landing were measured,
      then the contents of dopamine (DA) and its metabolites, 3, 4
      dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in the striatum
      were analyzed by HPLC-fluorescence detection. RESULTS: In comparison with
      control, there were significant differences in all neurobehavioral indexes (P <
      0.05). The contents of DA in ACR exposed group decreased by 65.64% compared with
      the control group (P < 0.05). However, no significant differences of DOPAC and
      HVA content were found between ACR exposed group and control group. CONCLUSION:
      Acrylamide may affect neurobehavior of rats and decrease the level of dopamine in
      striatum, thus induce a series of neurotoxic effects.

PMID- 21861344
TI  - [Structural equation model analysis on psychological resilience of left-behind
      children in rural areas in Sichuan Province].
AB  - OBJECTIVE: To explore the influencing factors on psychological resilience of left
      behind children in rural areas and to find protective factors for psychological
      resilience by Structural Equation Model. METHODS: 349 left-behind children of two
      rural middle schools in Zizhong County, Sichuan Province were measured in group
      by the Social Support Appraisals (SS-A) Scale and California Health Kids Survey
      Resilience Assessment Module (HKRA) and other appraisal scales as well as cross
      section investigated by self-made questionnaire, using Structural Equation Model
      for statistical analysis. RESULTS: Psychological resilience of left-behind
      children in rural areas was divided into two parts which were external protective
      factor and internal characteristic of individual. The latter was directly
      impacted by the former (beta = 1.138, P < 0.001) and gender (beta = 0.086, P =
      0.048). External protective factor of psychological resilience was directly
      impacted by family support (beta = 0.076, P = 0.047), parents concern (beta =
      0.092, P < 0.001), parental relationship (beta = 0.024, P = 0.043) and mother
      requiring (beta = 0.050, P = 0.065) and indirectly impacted by friends support,
      other support, the time of mothers working outside and guardian requiring. There
      was positive relationship between academic performance and internal
      characteristics of psychological resilience of left-behind children (r = 0.026, P
      = 0.055). CONCLUSION: Psychological resilience of left-behind children in rural
      areas was influenced by multidimensional factors. Family support, especially
      mother's care was the key protective factor. Guardians, teachers and friends
      support and care were also protective factors. Gender difference occurred as to
      internal characteristic of psychological resilience of the female left-behind
      children was higher than that of the male.

PMID- 21861345
TI  - [Energy zero balance study on the energy intake of healthy adults engaged in
      light physical activities in southern China].
AB  - OBJECTIVE: Using an energy zero balance method to investigate and analyze the
      level of dietary energy intake of healthy adults in southern China, in order to
      provide basic data for revising Chinese energy DRIs. METHODS: A total of 32
      healthy adults engaged in light physical activities were recruited randomly. The
      food intake of each subject including meals and snacks was weighed and made
      records at same days intervals in a period of 2 month (covering Monday to Sunday
      of a week). The energy intake was calculated and adjusted with the change of body
      weight according to the energy balance principle. RESULTS: The average total
      energy intake of subjects in energy zero balance was (8.895 +/- 1.535) MJ/d,
      (10.070 +/- 1.150) MJ/d for male and (7.719 +/- 0.765) MJ/d for female.
      CONCLUSION: The energy intake of healthy adults at zero balance could be measured
      at same days intervals within a 2 month period. The method was convenient,
      economical, available and practicable.

PMID- 21861346
TI  - [Evaluation on the dietary quality of pregnant women with an adjusted dietary
      balance index].
AB  - OBJECTIVE: In order to provide guidance for prenatal diet effectively, an
      adjusted evaluation system of dietary balance index (DBI) was developed for rapid
      assessment of the dietary intake of pregnant women in Hefei area. METHODS: A
      total of 342 representative pregnant women during the second or third trimester
      were selected from a hospital in Hefei. Food intakes were collected by a food
      frequency questionnaire, and the dietary quality was evaluated by an adjusted DBI
      07 scoring and evaluation system. RESULTS: From the distribution of DBI scores,
      the intake of beans, dairy products and food rich in iron of most pregnant women
      were far below the RNI, the intake of vegetables and fruits of pregnant women
      approaching and reaching RNI accounted for 72.2%, the intake of grain and animal
      food was insufficient or excessive, and the degree of inadequacy was more than
      excess. The taste of most pregnant women was light and moderate. Most of pregnant
      women took vegetable oil, no alcohol, but the diversity of their diet was not
      good enough. The quality of diet was also related to educational level.
      CONCLUSION: The dietary quality of pregnant woman could be reflected by using DBI
      evaluation system, by which the existing problems could be discovered in time.

PMID- 21861347
TI  - [Study on change of behavioral stages on nutritional intervention in farmers].
AB  - OBJECTIVE: To explore the applying stages of change model on nutrition
      intervention on "eating more vegetables and fruits, eating less salt" in farmers,
      and evaluate the change of behavioral stages. METHODS: The questionnaires were
      used to do baseline and evaluation survey on 500 farmers in trial group and
      control group respectively. Applying stages of change model to divide farmers
      into five stages according to their behavior of eating more vegetables and
      fruits. The intervention ways were used in trial group, especially in five stages
      farmers. After one year,the changes of behavioral stages in two groups were
      evaluated. RESULTS: There were statistical significance on proportion of
      behavioral stages between before intervention and after intervention in trial
      group (P < 0.05): the upgrade of behavior stages has been gained, the proportion
      of preparation, action, maintenance increased by 15.1%, 20.7% and 16.1% for
      eating more vegetables and fruits. With the rise of behavioral stage, the
      awareness rates of healthy knowledge, the average daily intake of vegetables and
      fruits, folic acid and urine potassium levels have rised, and the average daily
      intake of salts, diastolic pressure, homocysteine and urine sodium levels have
      reduced increasingly (P < 0.05). CONCLUSION: After intervention, through applying
      SOC model to analyse and show that the proportion of behavioral stages about
      eating more vegetables and fruits on farmers have changed from precontemplation
      to action and maintenance, the upgrade of behavior stages has been gained; The
      higher stages farmers have higher levels of heathy knowledge, more positive
      healthy belief and attitude, lower risk factors of chronic diseases than the
      lower stages farmers, the stages of change model has the practicability on
      behavior change.

PMID- 21861348
TI  - [FABP2 gene polymorphism and metabolic disorder of lipids in the middle aged and
      aged population].
AB  - OBJECTIVE: To learn the gene distribution of fatty acid binding protein gene
      (FABP2) and the mutation frequency of wild type A54T in FABP2 gene in the people
      with abnormal lipid metabolism to detect from molecular level the relationship
      between FABP2 gene polymorphism and metabolic disorder of lipids, and to
      investigate genetic factors and the pathogenesis of lipid metabolic disorders in
      the middle aged and aged people. METHODS: The polymorphism of FABP2 gene was
      analyzed by RELP (Restriction fragment length polymorphism) technique. The
      relationship between FABP2 polymorphism and the risk of dyslipidemia in 410
      middle aged and aged people was investigated. RESULTS: Mutation frequency of
      FABP2 gene in the people with dyslipidemia was 71.9%, significantly higher than
      that in the people with normal blood lipids (P < 0.05). Compared with individuals
      with wild type homozygote (Ala54/Ala54), the serum TC and TG of individuals with
      mutational heterozygote (Ala54/Thr54) or mutational homozygote (Thr54/Thr54) were
      distinctly higher, and serum HDL-C of them were distinctly lower (P < 0.05).
      CONCLUSION: FABP2 gene polymorphism might be one of factors for genetic
      susceptibility in metabolic disorder of lipids. The risk of occurring lipid
      metabolic disorders in individuals carrying mutational FABP2 gene (Ala54/Thr54,
      Thr54/Thr54) might be higher than those carrying wild type homozygote (Ala54/
      Ala54) while exposed to the same environment.

PMID- 21861349
TI  - [Analysis of correlation between serum somatostatin levels, antioxidant index and
      metabolic syndrome].
AB  - OBJECTIVE: To investigate serum somatostatin levels, antioxidant index in
      metabolic syndrome (MS). METHODS: Serum somatostatin levels, glucose, lipid level
      and certain antioxidant indexes were measured in the serum of 39 patients with
      MS, 60 MS high risk subjects (MSR) and 41 normal controls (NC). The associations
      of somatostatin with atherosclerotic index (AI), HOMA-IR and malondialdehyde
      (MDA) were analyzed. RESULTS: (1) Median somatostatin levels were lower in
      subjects with MS or MSR than in control subjects. (2) The activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased in
      subjects with MS or MSR compared with NC (P < 0.05). (3) A significant inverse
      relationships between somatostatin level and AI (r = -0.24, P < 0.01), HOMA-IR (r
      = -0.23, P < 0.05), and MDA (r = -0.25, P < 0.01) were observed. CONCLUSIONS: The
      severity of serum glucose and lipid disorders and oxidative stress was
      accompanied with decreased somatostatin levels. These results suggest a possible
      role of decreased somatostatin on MS generation.

PMID- 21861350
TI  - [Effects of inorganic arsenic on mRNA expression of Nrf2 and Nrf2-regulated
      downstream anti-oxidant enzymes in Chang hepatocytes].
AB  - OBJECTIVE: To study the effects of inorganic arsenic on mRNA expression of
      transcription factor Nrf2 and Nrf2-regulated downstream anti-oxidant enzymes,
      NADPH: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1(HO-1) in Chang
      hepatocytes. METHODS: Chang hepatocytes were treated with 5, 10, 25 and 50
      micromol/L of sodium arsenite (NaAsO2) for 6h, and RT-PCR were then performed to
      detect the mRNA expression of Nrf2, NQO1 and HO-1. RESULTS: When exposed to 5,
      10, 25 and 50 micromol/L of NaAsO2, Nrf2 mRNA were (100.74 +/- 3.70)%, (105.96 +/
      1.75)%, (101.76 +/- 1.01)% and (101.81 +/- 6.33)% of control,showing no
      statistic significance (P > 0.05). NQO1 mRNA expression were significantly
      increased (P < 0.05), and the levels of NQO1 mRNA were (106.52 +/- 3.11)%,
      (113.27 +/- 2.84)%, (111.96 +/- 6.96)% and (107.33 +/- 2.76)% of control,
      respectively. Moreover, HO-1 mRNA expression were also significantly induced by
      sodium arsenite exposure, and a definite dose-effect relationship was confirmed
      (P < 0.01). CONCLUSION: No elevation of Nrf2 transcription was found, while
      inorganic arsenic could increase the Nrf2-regulated NQO1 and HO-1 mRNA expression
      in human hepatocytes.

PMID- 21861351
TI  - [Interaction of plasma selenium levels and D12S304 gene site in the pathogenesis
      of Kashin-Beck disease analyzed by multifactor dimensionality reduction
      software].
AB  - OBJECTIVE: To explore the interaction of plasma selenium levels and D12S304 gene
      site in the pathogenesis of Kashin-Beck disease (KBD). METHODS: Case-control
      design was taken to compare the difference of plasma selenium levels and genotype
      of D12S304 between KBD patients and non-patients, and the interactions were
      analyzed by MDR software. RESULTS: Plasma selenium levels was lower in the case
      group than in the control group, while the D12S304 gene site was not different
      between the two groups, and no interaction between plasma selenium and genotype
      was observed. CONCLUSION: There was no interaction between plasma selenium and
      genotype at D12S304. Enlarging sample size or selecting another gene site might
      be needed in exploring the gene-environment interactions in the pathogenesis of
      KBD.

PMID- 21861352
TI  - [Pathways causing the disease of coal-burning fluorosis in southwest China].
AB  - OBJECTIVE: To find the pathways for coal-burning fluorosis and the main
      difference between severe fluorosis area and non-fluorosis area in southwest
      China. METHODS: The teeth health condition and diet structure of a total of 405
      children and 14 adults were investigated by Dean's method recommended by WHO and
      questionnaire. RESULTS: There was evident difference in diet structure between
      dental fluorosis patients and healthy population. The dental fluorosis prevalence
      rates of population living on corn roasted with open oven rapidly before the age
      of 6, even if lived in monitoring spots of improved oven for defluorination, in
      which the fluoride concentration of indoor air had meet the Chinese National
      Standard, was 100%, and most were in moderate to severe stages. The dental
      fluorosis prevalence rates of population living on non-roasted corn or rice was
      very low, most of which were in very mild stages. CONCLUSIONS: Living on roasted
      foodstuffs is the main pathologic cause of endemic fluorosis of population in
      southwest China.

PMID- 21861353
TI  - [Contribution of environmental lead exposure to blood lead level among infants
      based on IEUBK model].
AB  - OBJECTIVE: To evaluate the influence of environmental lead exposure on infant's
      blood lead through integrated exposure uptake biokinetic model for lead in
      children (IEUBK) model, based on environmental lead and prenatal lead exposure.
      METHODS: The data is from a prospective study conducted among pregnant women
      during 2005 -2007. Blood lead of the pregnant women in the late pregnancy,
      environmental lead values including lead concentration in soil, air and drink
      water were measured. Moreover, the blood lead concentrations of infants were
      measured as well. RESULTS: Infants were exposed to lead from the pregnant women
      during the pregnancy, and in the late pregnancy the geometric mean blood lead of
      pregnant women was (40.3 +/- 3.7) microg/L. The geometric mean blood lead
      concentration of six-month old infants was (54.7 +/- 6.7) microg/L and there were
      17.3% infants whose blood lead concentration were above 100 microg/L. Lead in
      soil,atmosphere and drink-water were 45.57 mg/kg, 0.023 microg/m3 and 3.25
      microg/L respectively. While based on the calculation of the IEUBK model, the
      value attributed to environmental lead exposure was 12.4 microg/L, accounting for
      22.7% of the real blood lead level. CONCLUSION: The results indicated that
      environmental lead contamination in the rural area might not be the main reason
      of elevation in blood lead among infants, other lead resources such as food lead
      exposure might be the major sources for the intake of lead among infants and
      should be paid more attentions in future.

PMID- 21861354
TI  - [Study on contamimation of endocrine disrupting chemicals in aquatic environment
      of Qiantang River].
AB  - OBJECTIVE: To study contamination of endocrine disrupting chemicals (EDCs) in
      aquatic environment of Qiantang River. METHODS: Carp vitellogenin (VTG) content
      in serum and ethoxyresorufin-o-deethylase (EROD) activity in liver of wild
      crucian, pesticide content including organic cholorine, organic phosphorus and
      pyrethroid in its muscle from 7 monitoring sites including Zhangtan (ZT), Jiekou
      (JK), Jiangjunyan (JJY), Yandongguan (YDG), Tonglu (TL), Fuyang (FY) and Yuanpu
      (YP) in Qiantang river were detected. And chemical analysis of water quality was
      carried on in four sites. RESULTS: EROD activity in crucian from ZT, JJY, FY and
      YP [(23.51 +/- 4.17), (16.79 +/- 7.39), (18.74 +/- 5.16), (18.65 +/- 8.86) nmol x
      g(-1) pro x min(-1), respectively] was significantly higher than that of control
      ((7.84 +/- 2.42) nmol x g(-1) pro x min(-1)), and VTG content in wild crucian
      from ZT, TL, FY and YP [(1.536 +/- 0.521), (16.404 +/- 13.579), (19.672 +/-
      16.354) and (17.079 +/- 18.397)] microg/ml, respectively) was significantly
      higher than that of control [(0.400 +/- 0.099) (microg/ ml]. No significantly
      difference in biomarkers was observed between other site and control. From high
      to low, in total organophosphorus, it was followed as: TL, YDG, YP, FY, QZ, JK,
      JJY (EPN was up to 2695.64, 611.96 microg/kg in TL and YDG, respectively). In
      total organochlorine: TL, YP, YDG, FY, QZ, JK and JJY (tetradifon content in
      muscle of wild crucian from TL was up to 3962.17 microg/kg). For pyrethroid
      pesticides: TL, YDG, YP, ZT, JK, FY and JJY (alpha-tetramethrin and alpha
      phenothrin was comparatively high in TL and YDG, up to 371.54, 239.62 microg/kg
      in the former, 416.23, 189.15 microg/kg in the latter, respectively). CONCLUSION:
      Aquatic environment of these sites including ZT, TL, FY and YP in Qiantang river
      received comparatively high EDCs, whose effects may be mainly due to pesticide
      pollution. Obvious organic contamination occurred in these sites including ZT,
      JJY, FY and YP. Changes of chemicals in water and EROD activity in fish test
      result are consistent with the actual contamination, while agricultural effluent
      discharges only affect the local River in the downstream. High PAH contamination
      in these sites such as ZT maybe lead to underestimation of estrogen effects,
      which was neglected easily, need be paid more attention to.

PMID- 21861355
TI  - [Effect of ambient air PM10 concentration on the hospital outpatient visit of
      respiratory diseases in Shenzhen City].
AB  - OBJECTIVE: To explore quantitatively the impact of the ambient air PM10
      concentration (inhalable particulate matter) on the hospital outpatients for
      respiratory diseases. METHODS: Daily hospital visits data in 2008 was collected
      from a hospital in Shenzhen, meteorological data and air pollution data were
      collected from Shenzhen Meteorological Bureau and Shenzhen Environmental
      Protection Bureau, respectively. There was a time serial analysis using semi
      parameter generalized additive model extend Poisson regression, after controlled
      with long-term tend, the-day-of-week, meteorological factors and other air
      pollutants. Excess relative risks (ER) of daily hospital visits associated with
      increased PM10 level were estimated. RESULTS: Ambient air PM10 concentration were
      no association with the increase of outpatients for respiratory in the same day.
      The lagged effect of 5 days with an ER of 1.113% (95% CI 0.613% - 1.616%) was
      observed. Except (PM10 + CO) model, the ER value increased when SO2, NO2, CO
      concentrations were introduced. CONCLUSION: The ambient air PM10 concentration
      could positively associated with the increase of daily hospital visits for
      respiratory diseases in Shenzhen.

PMID- 21861356
TI  - [Study of influential factors about trait coping style and the correlation
      between it and anxiety and depression in different student groups in Bengbu
      district].
AB  - OBJECTIVE: To investigate the coping style and their influential factors in
      different student groups. METHODS: Use stratified and random cluster sampling to
      collect 7315 students in seven high school and mid-schools in Bengbu district.
      The valid questionnaires were 7104. In these students, there were 1919 junior
      schools students, 1865 high school students, and boys were 3533, girls were 3571.
      Age from 12 to 22. The questionnaires which contained demographic
      characteristics, family factors and multidimensional sub-health questionnaire of
      adolescents (MSQA) were used to test these students. The single factor analysis
      and Regression analysis were analyzed by SPSS (statistical package for social
      science) 13.0. RESULTS: There were significance difference between positive
      coping style, negative coping style and fathers' and mothers' education (P <
      0.01). There were significance difference between positive coping style and the
      parents' expectations (P < 0.01). The patients' education, friends, characters
      and coping style were positively correlated (P < 0.01). There were correlation
      between coping styles and anxiety and depression (P < 0.01). There were positive
      correlation between passive coping style and anxiety and depression (P < 0.01),
      and there were negative correlation between active coping style (P < 0.01).
      CONCLUSION: There was relationship between patients' education, friends,
      characters and adolescents' coping style, and there were high correlation between
      coping style and anxiety and depression. Enhance capacity to respond actively and
      cultivate optimistic attitude of learning were help to maintain and improve their
      positive coping style.

PMID- 21861357
TI  - [Effects of enzymatic bone powder on calcium absorption and bone density in
      rats].
AB  - OBJECTIVE: To identify the influence of enzymatic cattle bone, enzymatic fish
      bone and ultrafine-enzymatic cattle bone on apparent calcium absorption rate and
      bone density in rats. METHODS: Female SD rats were randomly divided into 9 groups
      with 10 rats in each group, and were fed with low- and high-enzymatic cattle bone
      diet, low- and high-enzymatic fish bone diet, low-and high-ultrafine-enzymatic
      cattle bone diet, low- and high-calcium carbonate diet and low calcium control
      diet for 13 weeks. The calcium content of the low and high experimental groups
      was 500 mg/100 g and 1000 mg/100 g, and the calcium content of the control group
      was 100 mg/100 g. 3-day calcium metabolic experiment was conducted by the end of
      the 3rd week. Bone density was assayed by the end of the 13th week. RESULTS: The
      apparent calcium absorption rate was related to the calcium content in diet in a
      range of 60.69% -65.84% in the low dose groups and 34.00% - 44.06% in the high
      dose groups. The apparent calcium absorption rate in experimental groups was
      obviously lower than that in the low calcium control group (P < 0.05). Bone
      density of rats in enzymatic cattle bone, enzymatic fish bone and ultrafine
      enzymatic cattle bone groups were obviously higher than that in calcium carbonate
      group at the same calcium content in diet (P < 0.05). CONCLUSIONS: According to
      the results of calcium apparent absorption rate and bone density, enzymatic
      cattle bone, enzymatic fish bone, ultrafine-enzymatic cattle bone, and calcium
      carbonate could be used as sources of calcium.

PMID- 21861358
TI  - [Effects of resveratrol on lipid metabolism in C57BL/6J mice].
AB  - OBJECTIVE: To investigate the effects of resveratrol on serum and liver lipids in
      C57BL/6J mice. METHODS: 30 male C57BL/6J mice were randomly assigned to the
      following three groups: control group given a normal diet, high-fat diet group
      and resveratrol group (22.5 mg/kg BW) were given high fat diet. the resveratrol
      were dissolved in 0.5% sodium carboxymethyl cellulose and were given to the
      Resveratrol group by intragastric administration. The levels of serum total
      cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL
      C), high-density lipoprotein cholesterol (HDL-C), the levels of TG and TC in
      liver, and the pathological changes of liver were measured after the treatment
      lasted for 8 weeks. RESULTS: The serum TC, LDL-C, HDL-C levels of high-fat diet
      and resveratrol groups were higher than those of control group (P < 0.05), and
      the serum TC and LDL-C levels of high-fat diet were also higher than those of
      resveratrol group (P < 0. 05). But the serum TG levels of high-fat diet and
      resveratrol groups were lower than those of control group (P < 0.05). The TC
      content of liver in high-fat diet group were higher than those of control and
      resveratrol groups (P < 0.05). CONCLUSION: The TC content in C57BL/6J mice can be
      decreased by resveratrol (22.5 mg/kg BW).

PMID- 21861359
TI  - [Effect of soybean isoflavones on the cognitive performance of mice deprived of
      sleeping for 72h].
AB  - OBJECTIVE: To study the effect and mechanism of Soybean Isoflavones (SIF) on the
      cognitive performance of female mice after sleep deprivation for 72h. METHOD:
      Forty female mice were randomly divided into 5 groups:the control, sleep
      deprivation control (SDC), and three SIF groups (SIF L, SIF M and SIF H). SIF
      groups were administered by intra-gastric injection of SIF 20, 40 and 80 mg/kg bw
      respectively for 30 days. The control and SDC groups were administered with equal
      volume of normal saline. The 72h SD mice model was induced by the single platform
      technique. The cognitive ability of mice was tested by Y-maze. Antioxidant
      indicators (CAT, MDA and T-AOC) and neurotransmitters (NO, Glu and Ach) in
      cerebra were measured. RESULT: Compared with the control group, the cognitive
      abilities, CAT activities, T-AOC and Ach levels were decreased and NO, MDA and
      GLu contents were increased in mice after sleep deprivation for 72h. Compared
      with the SDC group, the cognitive abilities were improved and Ach contents were
      increased in SIF M and SIF H groups, T-AOC levels were improved in three SIF
      groups. CAT activities, MDA, NO and Glu contents were decreased in SIF H group
      only. CONCLUSION: The cognitive ability of 72h SD female mice could be improved
      by SIF, the mechanism of which might be involved in increasing antioxidant
      function, decreasing the damage of free radicals on cranial nerves and adjusting
      the neuron transmitter of cerebra.

PMID- 21861360
TI  - [Study on ultraviolet-screening effect of extracts from mangosteen (Garcinia
      mangostana Linn.) pericarp].
AB  - OBJECTIVE: To analyze the ultraviolet-screening of the n-butanol extracts of
      mangosteen pericarp and alpha-mangostin, compare the ultraviolet-screening effect
      of the extracts with rutin and ultramicro-titanium dioxide (TiO2). METHODS: The
      samples (n-butanol extract from mangosteen pericarp, alpha-mangostin, rutin and
      TiO2) were scanned at different wavelength and Pan-wavelength by ultraviolet
      spectrophotometry. RESULTS: The n-butanol extracts and alpha-mangostin had
      relatively satisfactory effects on ultraviolet-screening when the concentration
      was over 0.40 mg/ml and the effects on ultraviolet-screening was better than
      TiO2. CONCLUSION: The n-butanol extracts and alpha-mangostin had a positive
      ultraviolet-screening activity which was better than TiO2.

PMID- 21861361
TI  - [Development of modified molecular beacon based real-time PCR assay for the rapid
      detection of Salmonella choleraesuis and Salmonella paratyphi C].
AB  - OBJECTIVE: To develop real-time PCR assay based on modified molecular beacon for
      simultaneous detection of S. choleraesuis and S. paratyphi C. The established
      method was applied to the rapid detection of S. choleraesuis in food and stool
      samples of food poisoning, and then was applied to the identification of
      Salmonella C. METHODS: Based on the sequences (CP000857.1) published in GenBank,
      Two sets of primers and modified molecular beacon were designed. The Real-time
      PCR assay for the simultaneous detection of S. paratyphi C and S. choleraesuis
      was developed with optimized PCR procedures and PCR components, while other 11
      different bacterial species were as the control. Then the sensitivity and
      specificity of the assay were tested using 77 Samonella strains. The assay was
      applied to the detection of 70 food samples. RESULTS: The limit of detection
      achieved was 10 fg/reaction or 20 CUF/reaction, Only Salmonella paratyphi C and
      Salmonella choleraesuis strains generated fluorescent signals. No cross-reaction
      was observed with other 11 bacterium, the sensitivity and specificity were both
      100%. No samples among 70 food samples were found Salmonella positive by both
      real-time PCR assay and traditional culture method. It could be finished within 2
      hours from template preparation to detection and the overall test would be
      finished within one day. CONCLUSION: The real-time PCR assay was rapid, sensitive
      and specific. It could be applied to the rapid diagnosis of S. paratyphi C and S.
      choleraesuis in food and stool samples of food poisoning and the identification
      of Salmonella C to guarantee food safety.

PMID- 21861362
TI  - [Role of ERK in the hormesis induced by cadmium chloride in HEK293 cells].
AB  - OBJECTIVE: To detect the role of ERK in the hormesis induced by cadmium chloride
      in HEK293 cells. METHODS: HEK293 cells were treated with CdCl2 of 0, 0.0005,
      0.005, 0.05, 0.5, 5, 50, 500 micromol/L for 12h and 24h. The ERK inhibitors
      (PD98059, U0126) and c-raf shRNA were added before the cell was treated with
      CdCl2. The proliferation viability was measured by thethiazolyl blue (MTT) and
      WST-8 assay. The level of the phosphorylated ERK and c-raf was examined with the
      western blot method. The level of c-fos, c-myc and c-raf mRNA was examined with
      RT-PCR. RESULTS: CdCl2 stimulated cell proliferation at lower concentrations
      (0.05 and 0.5 micromol/L) but inhibit it at higher concentrations (50 and 500
      micromol/L). The c-fos mRNA increased significantly at low concentrations (0.51
      micromol/L) and the c-myc mRNA increased with CdCl2 concentration. Treated with
      100 micromol/L ERK1/2 inhibitor and c-raf shRNA, the cell proliferation did not
      increase significantly at low concentrations (0.05 and 0.51 micromol/L), but
      still decreased at high concentrations (50 and 500 micromol/L). CONCLUSION: CdCl2
      can induce the hormesis of HEK293 cell proliferation. The c-fos of ERK pathway
      may be involved in the biphasic effect induced by CdCl2.

PMID- 21861363
TI  - [Study on the enhancement diphacinone-europium fluorescence system and
      application for determination of the residue in urine].
AB  - OBJECTIVE: To establish an accurate, convenient and sensitive quantitative
      fluorescence method for the determination of diphacinone (DPN) in urine. METHODS:
      Diphacinone was complexed with europium ion (Eu3+) at the presence of DL
      histidine, polyvinylpyrrolidone (PVP) and ammonia-ammonium chloride (NH3 -NH4 Cl)
      buffer solution to form a multiple complex of DPN-Eu(3+) -DL-histidine-NH3-PVP
      fluorescence system, and the fluorescence sensitivity was greatly enhanced by the
      rare earth element of yttrium ion (Y3+ ). The excitation and emission wavelengths
      were 330 nm and 612 nm, respectively. RESULTS: The optimum conditions were Eu3+
      10.0 mg/L,Y3+ 20.0 mg/L, DL-histidine 0.01%, PVP 0.05% at pH 9.0. Under the
      optimum conditions, fluorescence intensity of the system was a linear function of
      the concentration of diphacinone in the range of 0.2 - 10.0 mg/L, the limit of
      quantification was 0.2 mg/L. The spiked recoveries for DPN in urine were 87.0% -
      97.3%, the intra-and inter-day RSDs were between 3.4% - 4.7% and 4.8% - 6.6%,
      respectively. CONCLUSION: The established method is simple, accurate and
      reliable, and it is satisfactory for the determination of DPN in urine and can be
      used for DPN poisoned patients for the rapid clinical diagnosis.

PMID- 21861364
TI  - [Lipids In Morphogenesis Of Mycelia-containing Fungi].

PMID- 21861365
TI  - [Catabolic Activities Of Formaldehyde Enzymes In Recombinant Strains Of Hansenula
      Polymorpha].

PMID- 21861366
TI  - [Chromate-resistant Mutants Of Yeast Pichia Guilliermondii: Isolation And
      Characterization].

PMID- 21861367
TI  - [Polymorphism In Sulfobacillus Thermosulfidooxidans Strains That Dominate In The
      High Temperature Oxidation Process Of Gold-Arsenic Concentrates].

PMID- 21861368
TI  - Phosphonoacetate biosynthesis: in vitro detection of a novel NADP(+)-dependent
      phosphonoacetaldehyde-oxidizing activity in cell-extracts of the marine
      Roseovarius nubinhibens ISM.
AB  - A novel phosphonoacetaldehyde-oxidizing activity was detected in cell-extracts of
      the marine bacterium Roseovarius nubinhibens ISM grown on 2-aminoethylphosphonic
      acid (2-AEP; ciliatine). Extracts also contained 2-AEP transaminase and
      phosphonoacetate hydrolase activities. These findings indicate the existence of a
      biological route from 2-AEP via phosphonoacetaldehyde for the production of
      phosphonoacetate, which has not previously been shown to be a natural product.
      The three enzymes appear to constitute a previously-unreported pathway for the
      mineralization of 2-AEP which is a potentially important source of phosphorus in
      the nutrient-stressed marine environment.

PMID- 21861369
TI  - [Study On 2-Methylpyridine Initial Catabolic Pathways In Arthrobacter Sp. KM-2MP
      Strain].

PMID- 21861370
TI  - [Ultrastructural Cell Changes Of Yarrowia Lipolytica Under Stress Conditions].

PMID- 21861371
TI  - Studies on pH and thermal stability of novel purified L-asparaginase from
      Pectobacterium carotojorum MTCC 1428.
AB  - Glutaminase free L-asparaginase is known to be an excellent anticancer agent. In
      the present study, the combined effect of pH and temperature on the performance
      of purified novel L-asparaginase from Pectobacterium carotovorum MTCC 1428 was
      studied under assay conditions using response surface methodology (RSM).
      Deactivation studies and thermodynamic parameters of this therapeutically
      important enzyme were also investigated. The optimum pH and temperature of the
      purified L-asparaginase were found to be 8.49 and 39.3 degrees C, respectively.
      The minimum deactivation rate constant (k(d)) and maximum half life (t1/2) were
      found to be 0.041 min(-1) and 16.9 h, respectively at pH of 8.6 and 40 degreesC.
      Thermodynamic parameters (deltaG, deltaH, deltaS, and activation energies) were
      also evaluated for purified L-asparaginase. The probable mechanism of
      deactivation of purified L-asparaginase was explained to an extent on the basis
      of deactivation studies and thermodynamic parameters.

PMID- 21861372
TI  - Kinetic study of partially purified cellulase enzyme produced by Trichoderma
      viride FCBP-142 and its hyperactive mutants.
AB  - Cellulases are the enzymes that cleave beta-1,4 linkages of cellulose, and
      carbohydrate that is main part of plants' cell walls. Presently, cellulase
      isolation and partial purification was executed through ammonium sulfate
      precipitation. The isolated protein of parental and derived mutants conferred
      molecular weights of 30, 45 and 55 kDa. The optimum temperature for maximal
      cellulase activity was 50 degrees C with Ea for substrate hydrolysis of 77.73,
      83.97 and 83.14 kJ mol(-1) and temperature quotient of 1.0020, 1.0022 and 1.0022
      by Trichoderma viride FCBP-142, Tv-UV-5.6 and Tv-Ch-4.3, respectively. The enzyme
      was stable at 50 degrees C for about 60 min but rapid denaturation occurred above
      55 degrees C. The enzyme showed optimum activity at pH 4.0 and involved two types
      of acidic and basic limbs with pKa1 and pKa2. The pKa1 of active site presented a
      significant shift from 2.55 to 2.9 and 3.1 by Tv-UV-5.6 and Tv-Ch-4.3,
      respectively in comparison to parental strain. Likewise, pKa2 moved from 6.05 to
      6.5 and 6.4. Enzyme kinetics displayed Michaelis-Menten constant Km 0.6, 0.5 and
      0.28 mg mL(-1) and Vmax value of 8.33, 10 and 9.09 Units mL(-1) for parental, Tv
      UV-5.6 and Tv-Ch-4.3, respectively.

PMID- 21861373
TI  - [Lipopolysaccharide From Budvicia Aquatica 97U124: Immunochemical Properties And
      Structure].

PMID- 21861374
TI  - [Effect Of Water Substrate Activity And Relative Air Humidity On Penicillium
      Chrysogenum Thom, Aspergillus Repens (Corda) Sacc., Trichoderma Viride Pers.,
      Isolated From Dwelling Premises].

PMID- 21861375
TI  - [Genetic Identification Of African Cultivated Saccharomyces yeast].

PMID- 21861376
TI  - Molecular and xylanolytic variation identified among strains of Pyrenophora
      graminea.
AB  - The inter-retrotransposon amplified polymorphism (IRAP) was used to confirm the
      genetic variation among 22 strains of Pyrenophora graminea differing in their
      xylanase production. A total of 162 bands were scored of which 151 (93.21%) were
      polymorphic. The molecular parameter used showed that P. graminea strains reside
      in four phylogenetic groups. There was observed the resolution between clustering
      strains and their xylanase production. Hence, the described approach presented
      here constitutes no prior assumption about the characterization of P. graminea
      strains differing in xylanase production.

PMID- 21861377
TI  - [Molecular Analysis Of Nitrifying Bacteria Diversity In Forest And Steppe Zones
      Of The European Part Of Russia].

PMID- 21861378
TI  - [Evaluation Of Taxonomic Diversity Of Stalk-producing Bacteria Of Genera
      Brevundimonas And Caulobacter Isolated From Various Eurasian Ecosystems Using 16S
      rRNA Analysis].

PMID- 21861379
TI  - Morphological and molecular characterization of Calothrix isolates obtained from
      diverse environments in India.
AB  - Abstract-Thirty cyanobacterial strains of Calothrix (family Rivulariaceae)
      isolated from diverse geographical regions of India were analyzed using
      morphological and molecular approaches. Most of the isolates were planktonic
      while some grew benthically. Significant differences were observed with regard to
      the shape and size of the vegetative cells, heterocysts, and akinetes. Analyses
      of molecular polymorphisms using Restriction Fragment Length Polymorphisms (RFLP)
      of 16S rRNA genes with the reference strain led to unambiguous differentiation of
      the isolates as well as understanding of their genetic relationships.

PMID- 21861380
TI  - [Micro- And Nanoparticles Of Condensed DNA Produced During PCR With Taq
      polymerase In Presence Of Plasmid Matrices].

PMID- 21861381
TI  - [New Phylogenetic Position Of Bacillus Intermedius 3-19 Strain].

PMID- 21861382
TI  - [Serotonin and impulsivity (experiments on animals)].
AB  - In the current paper a role of the serotinergic system in organization of
      impulsive behaviour in animals was considered. The results of influence of
      antagonists and agonists of the different types and subtypes of 5-HT receptors
      (1A, B; 2A, B, C; 7) and the effects of the dorsal raphe nuclei lesions on
      characteristics of impulsivity related with a motor control, mechanisms of
      attention, reinforcement and decision making were summarized. The data on knock
      out animals and the experiments with microdialysis have been also considered.
      There was emphasized the important role of interaction of 5-HT-, dopamine- and
      glutamatergic systems in mediation of impulsive behaviour.

PMID- 21861383
TI  - [Two-faced nitric oxide is necessary for both erasure and consolidation of
      memory].
AB  - One of ways of nitric oxide (NO) influence on neuronal activity is S
      nitrosylation, the covalent attachment of NO group to the thiol side chain of
      cysteine, changes function of existing proteins, inhibiting their normal role in
      physiological functions including memory. Influence of NO via GC activates
      intracellular signaling cascades and triggers increased synthesis ofproteins,
      influencing the memory. In the present paper we want to express and test the
      hypothesis that the NO is necessary both for erasure and development of memory.
      In our experiments in terrestrial snail Helix we tested the idea that NO besides
      well shown participation in memory development is involved in erasure/lockout of
      memory during relearning and reconsolidation.

PMID- 21861384
TI  - [Individual typological differences in human behavior under conditions of reward
      choice assoicated with risk].
AB  - A choice between probability (100, 75, 50, 25, 10, 0%) and valuable reward were
      investigated in adult. In behavioral experiments, adult subjects put in a
      situation of a choice between greater, but risky prize and smaller, but received
      always, made the decision according to situational factors and specific features
      of character such as propensity to risk and care. In a situation of choice of
      behavioral strategy, subjects could be divided in "inclined to risk" and
      "careful". Tipologycal differences between groups were the greatest under
      conditions of 25% probability of getting a valuable reward. Probability prognosis
      was more efficient in persons "tended to risk", than in "careful" subjects.
      According to psychological tests, "impulsive" people appeared to be more inclined
      to risk than to cautiousness. For the group of persons that tended to
      cautiousness under conditions of 25% probability of getting a valuable reward,
      synchronism of EEG rhythms in the alpha and beta bands was revealed.

PMID- 21861385
TI  - [Forecast ability of the auditory system during perception of gradually or
      abruptly moving short sound images].
AB  - The ability to localize endpoints of sound image trajectories was studied in
      comparison with stationary sound image positions. Sound images moved either
      gradually or abruptly to the left or right from the head midline. Different types
      of sound image movement were simulated by manipulating the interaural time delay.
      Subjects were asked to estimate the position of the virtual sound source, using
      the graphic tablet. It was revealed that the perceived endpoints of the moving
      sound image trajectories, like stationary stimulus positions, depended on the
      interaural time delay. The perceived endpoints of the moving sound images
      simulated by stimuli with the final interaural time delay lower than 200 micros
      were displaced further from the head midline as compared to stationary stimuli of
      the same interaural time delays. This forward displacement of the perceived
      position of the moving target can be considered as "representational momentum"
      and can be explained by mental extrapolation of the dynamic information, which is
      necessary for successive sensorimotor coordination. For interaural time delays
      above 400 micros, final positions of gradually and abruptly moving sound sources
      were closer to the head midline than corresponding stationary sound image
      position. When comparing the results of both duration conditions, it was shown
      that in case of longer stimuli the endpoints of gradually moving sound images
      were lateralized further from the head midline for interaural time delays above
      400 micros.

PMID- 21861386
TI  - [Perception of emotional intonation of noisy speech signal with different
      acoustic parameters by adults of different age and gender].
AB  - The listener-distinctive features of recognition of different emotional
      intonations (positive, negative and neutral) of male and female speakers in the
      presence or absence of background noise were studied in 49 adults aged 20-79
      years. In all the listeners noise produced the most pronounced decrease in
      recognition accuracy for positive emotional intonation ("joy") as compared to
      other intonations, whereas it did not influence the recognition accuracy of
      "anger" in 65-79-year-old listeners. The higher emotion recognition rates of a
      noisy signal were observed for speech emotional intonations expressed by female
      speakers. Acoustic characteristics of noisy and clear speech signals underlying
      perception of speech emotional prosody were found for adult listeners of
      different age and gender.

PMID- 21861387
TI  - [Experimental evidence for simultaneous existence of two dominantas in the
      central nervous system].
AB  - For the first time a possibility of simultaneous existence of two dominants was
      demonstrated: the polarization in the cortical representation of the forelimb and
      the dominanta of hunger. The two foci of stable excitation were created at the
      subthreshold level. A sound stimulus simultaneously produced a movement of the
      forelimb and a gulp. Manifestation of the two dominantas could be observed over
      the course of the experiment (about 1 h).

PMID- 21861388
TI  - [Sleep deprivation effect upon spatial memory consolidation in rats after one-day
      learning in a Morris water maze].
AB  - The effect of sleep deprivation by 'carousel' method on spatial memory
      consolidation in a Morris water maze was studied in Wistar male rats after one
      day learning (in accordance to a protocol by Frick et al., 2000). It was found
      that after fast 3-hr learning the memory trace retains during 24-hr. Twenty four
      hour sleep deprivation followed learning impaired consolidation of spatial
      memory. So the rat model of a one-day learning is suitable for the studying of
      neurophysiological mechanisms of sleep deprivation effects on spatial memory
      consolidation.

PMID- 21861389
TI  - [Behavior in the forced-swimming test and expression of BDNF and Bcl-xl genes in
      the rat brain].
AB  - A single exposure of rats to the forced-swimming stress decreased BDNF mRNA
      levels in the cortex and increased Bcl-xl gene expression in the hippocampus and
      amygdala 24 h after the stress. The animals demonstrated a depressive-like
      behavior and elevated blood corticosterone level. There was a significant
      negative correlation between BDNF mRNA level in the cortex and immobility time
      during swimming. Repeated exposure to swimming stress caused the elevation of the
      hippocampal BDNF mRNA level assessed 24 h after the second swimming session. The
      data suggest that stress-induced down-regulation of cortical BDNF gene expression
      and behavioral despair in the forced-swimming test may be interrelated. The
      increase in the BDNF and Bcl-xl mRNA levels may contribute to the mechanisms
      protecting the brain against negative effects of stress.

PMID- 21861390
TI  - [Differences in behavior of impulsive and self-controlled rats in the open-field
      and light-dark tests].
AB  - The aim of the study was to reveal the relationship between impulsive behavior in
      rats, on the one hand, and locomotor activity and emotionality on the other hand.
      Rats were divided into groups according to their preference for reinforcements of
      different values. Animals that preferred valuable but delayed reinforcement in
      more than 60% of cases formed a self-controlled group, whereas rats that selected
      poor but immediate reinforcements in more than 60% of the cases were considered
      as impulsive. The two groups of animals were subjected to the "open field" and
      "light-dark" tests. The impulsive animals more quickly adapted to new
      surroundings and displayed more pronounced research activity as compared to the
      self-controlled animals. The level of anxiety was higher in the self-controlled
      group.

PMID- 21861391
TI  - [Influence of anxiolytic afobazole on amygdalar neuronal activity and behavior of
      rabbits in emotionally negative situations].
AB  - The influence of systemic injection of anxiolytic afobazole (1 mg/kg) on
      interaction between neurons of the basal and central amygdaloor nuclei and
      behavior of rabbits in negative emotional situations was studied in order to
      reveal characteristics of amygdalar neuronal network properties during
      unconditioned fear. An afobazole injection results in a prolongation of stay in
      the light compartment of dark-light chamber, in a decrease in freezing
      probability after exposure of emotional stimuli, in appearance of some aggressive
      reactions in open field. Behavioral alterations were accompanied by duration
      increase and latency changes of amygdalar neuronal inhibitory interactions, by
      increase of probability of neuronal interactions on delta-range frequency, by
      decrease of interactions on theta-range frequency. Under the influence of
      afobazole the asymmetry with right dominance in interhemispheric interaction of
      amygdalar neurons decreased. Changes in network properties ofamygdalar neurons
      during afobazole injection testify to reduction of activation level of this
      structure taking place at the expense of enhancement of inhibitory interactions
      between neurons.

PMID- 21861392
TI  - [The features of sleep homeostasis in pregnant rats].
AB  - To investigate the effects of short-term sleep deprivation on the sleep pattern
      during pregnancy, cortical and hippocampal EEG and locomotor activity were
      recorded within 24-hours in a "disk-over-water" paradigm in 18 Wistar rats. Rats
      were adapted to experimental situation and were able to move across the rotating
      disk without falling in water. Then a polysomnogram was recorded for 3 sequential
      days in the control group 1 (n = 12) without disk rotation. On the next day non
      pregnant rats (experimental group 1, n = 6) were subjected to the sleep
      deprivation procedure with a pre-set program of disk rotation from 11:00 to 14:00
      during 3 sequential days. Other 6 rats (experimental group 2) were subjected to
      sleep deprivation on the 5-7th day of pregnancy. EEG and locomotor activity were
      also constantly recorded during the sleep deprivation procedure. In control group
      2 (n = 6, without sleep deprivation), a polysomnogram was recorded on the 5-7th
      day of pregnancy. As compared to non-pregnant rats, sleep intensity of pregnant
      rats increased during the first hours after the deprivation, and a considerable
      rebound of REM sleep took place. Sleep pattern during the off-light 12 hours
      remained unchanged. The results suggest that homeostatic compensation of sleep
      deprivation effects in rats on the first week of pregnancy is more efficient than
      in control non-pregnant animals.

PMID- 21861393
TI  - [GABAergic modulation of the oscillatory activity in the medial septal area
      during epilepsy].
AB  - On brain slices from healthy guinea pigs and animals with a model of chronic
      temporal lobe epilepsy, a comparative study of GABAergic modulation of
      oscillatory activity of neurons in the medial septal area was carried out. Under
      the action of GABA, burst activity persisted only in pacemakers in both groups of
      preparations. In epilepsy, the effectiveness of GABA action on the rhythmic
      neurons sharply increased. In the control group, GABA significantly reduced
      bursts frequency in cells preserving their oscillatory activity, whereas in
      slices from the epileptic brain burst frequency increased under the action of
      GABA. Blockade of GABAergic receptors led to a disruption of tonic GABAergic
      intraseptal influences and to a significant decrease in the effectiveness of
      blockers in epilepsy. The study was the first to demonstrate a dysfunction of the
      septal GABAergic system in temporal lobe epilepsy, which is a possible cause of a
      sharp change in the oscillatory properties of septal neurons. These findings
      contribute to elucidation of the mechanisms of temporal lobe epilepsy.

PMID- 21861394
TI  - [Reflections on public health, medicine, and art of healing (untimely thoughts of
      an old doctor)].

PMID- 21861395
TI  - [Melatonin as a most important factor of natural electromagnetic fields impacting
      patients with hypertensive disease and coronary heart disease. Part 1].
AB  - Part 1 of this review is devoted to modern concepts of mechanisms of action of
      weak natural and artificial electromagnetic fields (EMF) on the cardiovascular
      system at the cellular, molecular, and atomic levels with the participation of
      Ca2+ and melatonin. EMF are known to affect Ca2+ homeostasis and suppress
      melatonin activity in a wide wavelength range. Ca2+ ions in pinealocytes are
      involved in regulation of cAMP synthesis that mediates conversion of serotonin
      into melatonin. Their leakage from pinealocytes results in a decrease of the cAMP
      level and thereby suppresses production of melatonin. At the same time, the
      cyclic circadian rhythm of melatonin secretion controls the overall activity of
      human body from eating to sleep and metabolism.

PMID- 21861396
TI  - [The genes of atherosclerosis and cardiovascular diseases].
AB  - The aim of the work was to study polymorphism of atherosclerosis-related genes in
      patients with different forms of coronary heart disease (CHD) and chronic
      cerebral ischemia (CCI) in comparison with long-living subjects. Analysis
      included the distribution of genotypes and alleles of functional polymorphisms of
      lipid metabolism genes, viz. HindIII--polymorphism of lipoproteinase (LPL) gene;
      HhaI--polymorphism of apoE gene; TaqIB--polymorphism of cholesterol ether
      transfer protein (CETP) gene; I/D--polymorphism of angiotensin converting enzyme
      (ACE) in CHD and CCI patients of different age groups including long livers and
      those presenting with different clinical variants of CHD and CCI (FC II-III
      stable angina of effort, acute myocardial infarction, post-infarction
      cardiosclerosis, acute coronary syndrome) and control subjects. The study
      revealed potential molecular-genetic markers for primary and secondary
      prophylaxis of CHD and CCI. It was shown that DD genotypes of ACE gene, H+/+ of
      LPL gene and E3E4 are associated with an enhanced probability of myocardial
      infarction (IM) in CHD patients and can be regarded as high risk markers. The DD
      genotype is associated with an increased risk of recurrent MI, life-threatening
      post-IM complications and severe cardiac insufficiency as well as peculiar
      personality and behavioural traits (animosity and type A behaviour)-
      psychological risk factors of CHD and predictors of delayed application for
      medical aid. E2 allele of the ApoE gene and H allele of the LPL gene occur much
      more frequently in CHD patients aged above 90 years (long livers) than in younger
      subjects; hence, their value as markers of stable ischemic disease. Protective
      effect in terms of favourable clinical course of CCI and life expectancy is
      especially pronounced in subjects with a combination of genotypes with E2E3 + H+H
      , E2E2 + H+H-, E3E3 + H-H-genes of ApoE and LPL. B2B2 genotype of CETP gene
      increases the risk of stable CCI and B1B1 genotype of CETP gene enhances
      predisposition to cardiovascular pathology.

PMID- 21861397
TI  - [Critical notes on the results of studies (ACCORD, ADVANCE, VADT) of the
      efficiency of intensive therapy of type 2 diabetes mellitus].
AB  - A brief review of results of prospective randomized studies on the efficacy of
      reduction of blood glucose levels for the prevention of type 2 diabetes mellitus
      complications delivered at the 68th Congress of American Diabetic Association
      (June 2008). They showed that normal glycemia is very difficult to reach and
      usually at the cost of side effects, in the first place hypoglycemia. Lowering
      glycemia to the near-normal level prevents development of nephropathy but fails
      to reduce the frequency of cardiovascular disease. The reduced risk of myocardial
      infarction was documented only in the ACCORD study. However, this effect was
      associated with a rise in general mortality that necessitated premature
      termination of this trial. Causes behind the enhanced mortality are discussed,
      recommendation are proposed ensuing from the results of the reviewed studies.

PMID- 21861398
TI  - [Aging, age-related diseases, and certain risk factors of cardiovascular diseases
      in subjects of advanced and senile age].
AB  - The aim of the work was to study sex-specific differences between certain risk
      factors of cardiovascular diseases and hemodynamic parameters in elderly subjects
      and their relation to age-specific diseases and genealogic history of longevity.
      Total cholesterol, triglyceride, glucose, fibrinogen, uric acid, urea, creatinine
      levels in plasma and arterial pressure (AP) were measured. Hemodynamic parameters
      were calculated by the formulas for the stroke volume, cardiac output, myocardial
      contractility, pulse pressure, total peripheral resistance (TPR), endurance
      factor of cardiac activity, and Kerdo index. Each new decade of life was
      characterized by peculiar hemodynamic patterns. Pulse AP (PAP) and TPR increased
      with age and was associated with sex-related metabolic changes. Elderly men
      presented with hypocholesterolemia and anemia. Total cholesterol, fibrinogen, and
      glucose levels did not correlate with age. To conclude, elevated PAP, TPR, and
      left ventricular hypertrophy are risk factors of cardiovascular diseases in old
      subjects. Combination of several risk factors in young and middle-age subjects
      reduces prognostic value of the longevity factor in the familial history. Aging
      is accompanied by the development of gender-related differences in metabolic
      parameters.

PMID- 21861399
TI  - [The frequency of primary and secondary myocardial infarction in various diseases
      of internal organs].
AB  - The age structure of myocardial infarction (IM) risk factors was elucidated in
      976 men of different age (396 with primary and 580 with secondary IM) residing in
      Sankt-Peterburg. It was shown that primary and especially secondary IM are
      associated with a variety of risk factors and concomitant pathologies. Three or
      more risk factors were identified in patients of both age groups especially those
      with secondary IM which suggests a high risk of coronary disease. The commonest
      concomitant conditions in men below 60 years were ulcer disease, other
      gastrointestinal diseases, and chronic bronchitis whereas chole- and urolithiasis
      prevailed in elder subjects (especially with secondary IM).

PMID- 21861400
TI  - [Clinical, metabolic, age-related, and biorhythmologic aspects of daily arterial
      pressure profiles in patients with arterial hypertension].
AB  - The work was designed to study daily arterial pressure (AP) profile in 103
      patients aged 20-70 (48.6 +/- 12.) years with grade I-II arterial hypertension
      and its relation to selected metabolic parameters, heliogeophysical factors and
      age. The patients underwent 24-hr AP monitoring, calculation of body mass index,
      measurement of blood glucose and cholesterol levels. Non-dippers showed higher
      mean nocturnal AP values than dippers probably due to higher BMI, glucose and
      cholesterol levels. These patients were more sensitive to heliophysical factors.
      Patients above 60 years displayed higher AP values in morning hours compared with
      21-40 year-old ones. These data can be used in the development of primary and
      secondary prophylaxis of arterial hypertension.

PMID- 21861401
TI  - [Dynamics of primary hemostasis activity in patients with arterial hypertension
      and metabolic syndrome treated with candesartan].
AB  - The aim of the study was to elucidate normalizing effect of candesartan on
      disturbed thrombocytic hemostasis in patients with arterial hypertension and
      metabolic syndrome. The drug was given for 16 weeks to 31 patients in whom
      dynamics of lipid peroxidation in plasma and platelets, the antioxidative
      potential of candesartan, and parameters of thrombocytic hemostasis were
      assessed. Treatment with candesartan improved lipid peroxidation and primary
      hemostasis. It is expected that continuation of therapy following this scheme can
      stabilize the obtained effect.

PMID- 21861402
TI  - [Assessment of the functional state of the right ventricle by radionuclide
      tomoventriculography].
AB  - The aim of this work was to evaluate the potential of radionuclide
      tomoventriculography (RTVG) for the study of the functional state of right
      ventricle (RV) in patients with thromboembolism of branches of the pulmonary
      artery (TEPA) or ventricular arrhythmias. A total of 96 patients were admitted
      for examination to the clinics of Research Institute of Cardiology, Siberian
      Division of Russian Academy of Medical Sciences in 2006-2008. They were divided
      into 3 groups. Group 1 (n = 40) included patients of mean age 62 +/- 11 years
      with non-massive TEPA, group 2 (n = 15) patients with coronary heart disease NYHA
      class I-II (50 +/- 9 years), group 3 (n = 4) children and adolescents 13.2 +/-
      3.7 years with ventricular extrasystole and/or monomorphic ventricular
      tachycardia. All patients were examined by ECG-synchronized RTVG. The study
      showed that this method can be used to efficaciously determine volume
      characteristics of right ventricle, ejection fraction, relationship between fast
      and slow filling phases, and intreventricular dyssynchronism. The functional
      ability of the right side of the heart in patients with minor lesions in the
      pulmonary vasculature should be regarded as a sign of acute thromboembolism and
      marked systole-diastolic dysfunction of right ventricle (under similar
      conditions) as a manifestation of chronic post-thromboembolic hypertension. The
      number of areas of asynchronous myocardial contractions and the degree of
      intraventricular dyssynchronism detected by RTVG positively correlate with the
      degree of contractile dysfunction of right ventricle. Scintiographic signs of
      intraventricular dyssynchronism suggest predominance of contractile heterogeneity
      of right ventricle over physiological one.

PMID- 21861403
TI  - [Coronary heart disease and oncological pathology].
AB  - This article highlights main pathogenetic links between coronary heart disease
      and oncological diseases including the role of apoptosis, paraneoplastic
      manifestations, and psychopathologic conditions as well as the influence of
      therapy on CHD progression. Relevant clinical observations to illustrate
      theoretical considerations are presented.

PMID- 21861404
TI  - [Sinus node activity in Parkinson's disease].
AB  - Results of evaluation of cardiac rhythm variability (CRV) in Parkinson's disease
      (PD) are presented. High-resolution rhythmocardiography with a KAP-RK-01-Mikor
      diagnostic system was used to register CRY, peripheral and autonomous
      dysregulation of pacemaker activity of the synoatrial node. Reduced CRV was
      documented in 107 PD patients of whom 26% exhibited synoatrial dysfunction. The
      temporal statistical and spectral analysis of CRV, comparison of its results with
      clinical data suggest dissociation between cerebral and peripheral vegetative
      effects in PD, relatively well preserved suprasegmental ergotropic regulatory
      afferent impacts, and inadequate vegetative control at the post-ganglionic level.

PMID- 21861405
TI  - [Parameters of oxidative stress in patients with gastric cancer].
AB  - We studied effect of the neoplastic process and surgical treatment on parameters
      of the oxidative system in patients with stomach cancer including serum and
      gastric tissue levels of malonic dialdehyde, lactic and pyruvic acids in stage I
      IV malignancy before and after radical surgery. The development and
      generalization of the neoplastic process are associated with the activation of
      oxidative reactions leading to endotoxicosis. Specific anticarcinogenic
      treatments (including surgery) aggravate changes in the oxidative systems and
      further deteriorate quality of life and tolerance of the treatment.

PMID- 21861406
TI  - [Modified therapy of herpetic infection].
AB  - The study demonstrates a higher pharmacotherapeutic and economic efficacy of an
      alternative treatment modality for genital herpes using cycloferon, an inducer of
      endogenous interferons, compared with acyclovir. Clinical remission due to
      suppression of virus replication occurred in 72.3 and 73.5% of the cases within 6
      months after the treatment with cycloferon and cycloferon + acyclovir
      respectively. Acyclovir alone prevented reactivation of the disease only in 128%
      of the patients. The cost/effectiveness ratio in patients given combined therapy
      was 27.95 compared with 12.9 in case of monotherapy with acyclovir which suggests
      economic feasibility of the use of cycloferon as the drug of choice for the
      management of genital herpes. The efficacy of therapy was identical in patients
      with and without deletion of the GSTM1 gene encoding glutathione-S-transferase
      which suggests the possibility to effectively use cycloferon in genetically
      heterogeneous patients.

PMID- 21861407
TI  - [Oxidative stress in patients with mechanical jaundice of different origin and
      severity].
AB  - This randomized clinical study included 118 patients with mechanical jaundice
      (MJ) of different origin and severity. It highlighted the role of free radical
      generation processes (FRP) in the development of the disease within 1 day after
      its onset. Disbalance of FRP affects oxygen and lipid components of oxidative
      stress and is especially well pronounced in severe cases and in patients with
      tumours. It becomes increasingly apparent with time from the onset of jaundice
      and endotoxicosis. FRP disbalance precedes clinical manifestation of jaundice and
      persists for a long time even after alleviation of its clinical symptoms. Certain
      signs have a prognostic values. Therapy with reamberin at a daily dose of 400 ml
      is shown to effectively correct oxidative stress associated with MJ of tumorous
      and non-tumorous origin regardless of the severity of the disease. Positive
      effect of antioxidative therapy is accompanied by the improvement of laboratory
      characteristics, clinical picture, and outcome of the disease.

PMID- 21861408
TI  - [Diagnostics of Achilles tendon ruptures].
AB  - This review is concerned with diagnostics, surgical and orthopedic treatment of
      fresh and long-standing Achilles tendon rupture. Despite seemingly easy
      diagnostics, different authors indicate that 15-29% of Achilles tendon rupture
      escape timely recognition which leads to inadequate treatment and its poor
      outcome. Hence, the importance of clinical tests permitting to improve
      diagnostics bearing in mind that such expensive methods as MRT are not readily
      available. We describe all (to our knowledge) clinical tests for the purpose as
      well as X-ray, ultrasonic, and MRT diagnostics (including differential) of
      Achilles tendon rupture.

PMID- 21861409
TI  - [Clinical and morphological features of infectious endocarditis in HIV-infected
      intravenous drug abusers].
AB  - The aim of this work was to study the clinical course and morphogenesis of
      infectious endocarditis in HIV-infected intravenous drug abusers. In this
      patients, endocarditis was an acute disease with high frequency of thromboembolic
      complications and ill-defined exudative component of the inflammatory reaction.
      Autopsies dated to 1993-2008 showed that neither the presence of morphological
      signs of early HIV infection nor chronic hepatitis C with minimal or moderate
      inflammation has an appreciable effect on the intrahospital mortality rate in
      these patients.

PMID- 21861410
TI  - [The Sankt-Peterburg Obukhovskaya city hospital (second half of the 19th
      century)].

PMID- 21861412
TI  - [Examination of risk factors for deep vein thrombosis following total hip
      arthroplasty].
AB  - BACKGROUND: Deep vein thrombosis (DVT) is the main cause of pulmonary thrombolism
      (PE). Thus by preventing DVT, the risk of PE can be greatly reduced. METHODS:
      Patients were divided into two groups: a group of patients who were affected with
      DVT after total hip arthroplasty (THA) and a group of patients who were not
      affected. To examine the risk factor for DVT after THA, a comparative analysis
      between these two groups was performed. RESULTS: According to the multivariate
      logistic regression analysis, the preoperative elevated value of D-dimer is a
      significant risk factor which is only relative to the onset of DVT after THA. In
      addition, it was suggested that the preoperative value of D-dimer could be used
      as a means to rule out DVT after THA. CONCLUSIONS: It is useful to investigate
      the preoperative value of D-dimer as a predictive factor for the occurrence of
      DVT after THA.

PMID- 21861411
TI  - [Comparison of intrathecal morphine and buprenorphine for postoperative analgesia
      in cesarean delivery].
AB  - BACKGROUND: It has become a popular practice to add opioids to spinal solutions
      to enhance and prolong intraoperative and postoperative analgesia in cesarean
      section. Morphine is the opioid most widely used for this purpose, but there are
      few reports about intrathecal buprenorphine. We evaluated the postoperative
      analgesic effect of intrathecal buprenorphine compared with intrathecal morphine
      after cesarean section. METHODS: We retrospectively compared group B (n = 20)
      receiving tetracaine 10mg plus intrathecal buprenorphine 0.05 mg with group M (n
      = 24) receiving tetracaine 10 mg with intrathecal morphine 0.1 mg in elective
      cesarean section under spinal anesthesia. RESULTS: There were no significant
      differences between the groups in time to first postoperative supplemental
      analgesics, times of using postoperative supplemental analgesics and antiemetics
      within 24 hours after operation, and the incidence of postoperative nausea and
      vomiting and pruritus. CONCLUSIONS: It is concluded that intrathecal
      buprenorphine 0.05 mg provides similar postoperative analgesic effect with
      intrathecal morphine 0.1 mg without any increases of side-effects in cesarean
      section.

PMID- 21861413
TI  - [Relationship between magnesium concentration in cerebrospinal fluid and delayed
      cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage].
AB  - BACKGROUND: The present study was conducted to determine the relationship between
      magnesium concentration in cerebrospinal fluid (CSF) and delayed cerebral
      ischemia (DCI) in patients with subarachnoid hemorrhage (SAH). METHODS: We
      studied 39 consecutive patients undergoing surgery after SAH. A spinal drainage
      catheter was inserted into the lower lumbar vertebrae before surgery. CSF was
      then sampled and the magnesium concentration measured. General clinical data,
      Hunt-Hess (H-H) grade and Fisher grade, aneurysm size and site, intracerebral and
      intraventricular hemorrhage, and blood glucose levels were all recorded on
      admission. At the same time, the Glasgow coma scale (GCS) score was calculated.
      Outcomes were assessed using the Glasgow outcome scale at discharge. DCI was
      defined as a two-point decrease in the GCS score and/or focal deficit, and was
      confirmed by cerebral angiography. The recorded values were expressed as the
      median (interquartile range). RESULTS: Of the 39 patients, 23 (59%) had DCI. The
      magnesium concentration in the DCI cases was 2.8 (2.7 and 2.9) mg x dl(-1), which
      was significantly lower than that in the non-DCI cases, i. e., 2.9 (2.8 and 3.0)
      mg x dl(-1) (P < 0.05). There were no significant differences in the other
      factors. CONCLUSIONS: The results indicate that preoperative hypomagnesemia
      within the CSF might play a role in the development of DCI in patients with SAH;
      however, further studies will be necessary to confirm this observation.

PMID- 21861414
TI  - [Intravenous patient-controlled analgesia (IV-PCA) for relief of postoperative
      pain].
AB  - Intravenous patient-controlled analgesia (IV-PCA) using opioids such as morphine
      and fentanyl can be an effective analgesic method for post-operative pain that is
      resistant to conventional administration of narcotic analgesics and nonsteroidal
      anti-inflammatory drugs, and where epidural block and peripheral nerve block are
      not feasible. In addition to post-operative pain relief, IV-PCA can facilitate
      early ambulation, reduce respiratory complications, and increase patient satis
      faction. However, respiratory and circulatory depression, and post-operative
      nausea and vomiting (PONV) often occur as side effects of IV-PCA with opioids.
      Administration of droperidol can be an effective treatment for PON.

PMID- 21861415
TI  - [Examination of the optimal midazolam dose required for loss of puncture memory
      at the time of spinal anesthesia].
AB  - BACKGROUND: We examined midazolam ED50 according to age that was necessary for
      loss of puncture memory at the time of spinal anesthesia and determined whether
      we could estimate the presence of puncture memory from the degree of sedation
      after midazolam administration. METHODS: We enrolled patients with ASA PS 1 or 2
      and patients from 50 to 80 years of age who had been planned for surgery with
      spinal anesthesia. We divided the patients into groups according to their age-
      50s, 60s, and 70s as L, M, and H groups, respectively. We evaluated the degree of
      sedation with six phases of scores after intravenous administration of midazolam
      and spinal anesthesia was performed. The midazolam dose was based on the ups and
      downs method. RESULTS: The midazolam ED50s required for the loss of puncture
      memory in groups L, M, and H were 0.043, 0.035, and 0.026 mg x kg(-1),
      respectively. We estimated the association between the sedation degree score
      after midazolam administration and the puncture memory from ROC curve, but AUC
      was 0.56 for all cases. CONCLUSIONS: The midazolam ED50 required for the loss of
      puncture memory decreased with age but it was difficult to estimate puncture
      memory from the degree of sedation.

PMID- 21861416
TI  - [Evaluation of the side effects of intravenous patient controlled analgesia after
      spine surgery].
AB  - BACKGROUND: We have adopted intrravenous patient controlled analgesia (IV-PCA)
      for spine surgery. We could not find reports about detailed examinations of the
      side effects of IV-PCA using morphine after spine surgery, so we investigated
      retrospectively side effects in cases using morphine IV-PCA. METHODS: Eighty-five
      patients underwent IV-PCA after spine surgery. The contents of PCA pump were
      morphine 20 mg (= 2 ml), droperidol 2 mg (= 0.8 ml), and saline 77 ml. We fixed
      continuous infusion at 2 ml x hr(-1), bolus infusion at 2 ml x hr(-1), and
      lockout time at 15 minutes. Respiration time, SpO2, blood pressure, pulse rate,
      nausea and vomiting, and VAS were monitored while IV-PCA was in use. When severe
      side effects were noticed, IV-PCA was discontinued by physician in charge. We
      judged discontinuation of IV-PCA as occurrence of severe side effects. RESULTS:
      IV-PCA was discontinued in seven patients. The causes of discontinuation were
      nausea and vomiting, hypotension, and bradycardia. Nausea and vomiting was the
      most common cause and found mostly in women. CONCLUSIONS: Because IV-PCA was
      discontinuated in 8.2% of patients, it was thought that its management depending
      on patients' personal state was necessary to utilize IV-PCA as a method of
      postoperative analgesia.

PMID- 21861417
TI  - [Anesthetic management of patients with pulmonary arterial hypertension (PAH)].
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with significant
      perioperative risk due to the severity of cardiac dysfunction related to the RV
      Tei index greater than 0.83. We evaluated the car- diovascular function during
      anesthesia to elucidate the characteristics of severity of PAH. METHODS: Nine
      patients undergoing central venous catheterization under general anesthesia
      (seven patients) and local anesthesia with sedation (two patients) were studied.
      RV Tei index of five patients were greater than 0.83 (severe) and in four
      patients RV Tei index was below 0.83 (moderate). Bioimpedance method was used to
      determine stroke volume (SV) and cardiac output (CO) non-invasively throughout
      anesthesia. The correlation between the changes in SV and CO was evaluated by
      using least squares method. RESULTS: Demographic data showed mean age of 16.6
      years, height of 146.9 cm and weight of 39.7 kg. Correlation coefficient of SV
      and CO in the patients with severe cardiac dysfunction was 0.0-0.21, while in
      those with moderate cardiac dysfunction it was 0.49-0.93. CONCLUSIONS: In
      patients with severe PAH, it was demonstrated that CO is maintained by the change
      in heart rate (HR) but not by SV It is suggested that the control of HR in
      patients with PAH is of clinical importance in order to maintain CO, if RV index
      is greater than 0.83.

PMID- 21861418
TI  - [Time course changes in perfusion index and pleth variability index during
      electroconvulsive therapy].
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a widely acceptable therapy for
      psychiatric symptoms. ECT provokes abrupt hemodynamic changes, and sometimes
      induces serious cardiac complications. In this study, we examined the time course
      of changes in perfusion index (PI) and pleth variability index (PVI) during ECT
      using Radical-7 (Masimo Corp., USA). METHODS: Fifteen patients with psychiatric
      disease treated with ECT were enrolled in this study. The study was performed at
      three or four treatment points for 10-12 treatments. Anesthesia was induced by
      propofol 0.8-1.0 mg x kg(-1), and suxamethonium 0.8-1.0 mg x kg(-1). Thereafter
      patients were ventilated by facial mask with 100% oxygen, and ECT was performed.
      All patients were monitored using hemodynamic variables, PI and PVI. Variables
      including PI and PVI were measured before and 5 minutes after ECT. Anti
      hypertensive agents were administered if necessary. RESULTS: Heart rate
      transiently increased after ECT. PI transiently decreased during ECT, but
      returned to baseline value 1 minute after ECT. PI was unchanged during the study
      period (awake state: PI 3.6 +/- 1.4, during ECT 1.6 +/- 0.9*, one minute after
      ECT 1.9 +/- 1.7,*: P < 0.05 compared with awake state). CONCLUSIONS: This finding
      suggests that tissue perfusion was transiently impaired during ECT.

PMID- 21861419
TI  - [Postoperative analgesia of continuous intravenous fentanyl or dexmedetomidine
      for patients receiving anticoagulant therapy].
AB  - BACKGROUND: It is difficult to achieve good postoperative analgesia in patients
      who undergo abdominal aortic surgery without epidural analgesia and who have a
      bleeding tendency or are undergoing anticoagulation therapy. Intravenous fentanyl
      analgesia can be used in such patients, but it occasionally causes respiratory
      depression. Dexmedetomidine is used to achieve postoperative sedation and
      analgesia without respiratory depression. We compared the methods used to achieve
      postoperative analgesia after abdominal aortic surgery. METHODS: In the
      intravenous fentanyl analgesia group (group F, n = 15), 0.5 microg x kg(-1) x hr(
      1) fentanyl infusion was initiated during operation and continued to the next
      morning. In the intravenous dexmedetomidine group (group D, n = 15), 0.4-0.7
      microg x kg(-1) x hr(-1) dexmedetomidine infusion was commenced during the
      operation and decreased to 0.2-0.7 microg x kg(-1) x hr- in the next morning. In
      the control group (group C, n = 15), continuous intravenous analgesia was not
      used. The frequency of analgesic use, Ramsay score, PaCO2 value, and rate of
      nausea and shivering were evaluated on the next morning. RESULTS: The frequency
      of analgesic use and Ramsay score were similar in groups F and D. The Paco2 value
      was higher in group F than group D. CONCLUSIONS: With regard to respiratory
      depression, intravenous dexmedetomidine analgesia is safer and more useful than
      intravenous fentanyl analgesia.

PMID- 21861420
TI  - [Submental tracheal intubation for a panfacial fracture patient].
AB  - Panfacial fractures represent a unique challenge to the surgical and anesthetic
      team. Often nasal and oral intubations interfere with surgical procedure, while
      tracheotomies include a number of potential complications as well as the
      formation of poor scarring in a highly visible area. Tracheal intubation through
      the floor of the mouth, mentioned as submental tracheal intubation, is a simple
      quick and effective alternative to oral and nasal tracheal intubation or
      tracheostomy in the surgical management of selected patients with panfacial
      fractures. In this case report, with successful submental tracheal intubation,
      the potential complications associated with a tracheotomy were avoided.

PMID- 21861421
TI  - [Cranial subdural hematoma with intracranial hypotension related to epidural
      anesthesia and Trendelenburg position: a case report].
AB  - We report a case of cranial subdural hematoma with intracranial hypotension. A 34
      year-old woman had laparoscopic ovarial cysterectomy under general anesthesia
      combined with epidural anesthesia. Two days later, she developed a severe
      headache and nausea. She underwent cranial magnetic resonance imaging (MRI)
      scanning, and was diagnosed with cranial subdural hematoma with intracranial
      hypotension. The patient had had no anticoagulant therapy before the surgery. She
      was managed conservatively with bed rest and additional intravenous infusion. Her
      symptoms gradually improved except a slight headache, and she was discharged on
      the 38th postoperative day. Intracranial hypotension is a syndrome characterized
      by orthostatic headaches and hypovolemia of cerebrospinal fluid (CSF). There were
      typical findings on MRI, which include linear enhancement of the pachymeninges,
      pituitary hyperemia and subdural hemorrhage. We thought that these were due to
      epidural anesthesia first, but there was no evidence of dural puncture. It was
      also considered that it is influenced by change in CSF pressure, and intracranial
      venous engorgement may be due to Trendelenburg position for several hours.
      Because cranial subdural hematoma is a life-threatening complication, it is
      necessary to reconsider application of epidural anesthesia for laparoscopic
      surgery with Trendelenburg position.

PMID- 21861422
TI  - [Patient-controlled epidural analgesia combined with patient-controlled
      intravenous analgesia for postoperative analgesia after Miles' operation for
      rectal cancer].
AB  - A 69-year-old woman (156 cm, 53 kg) underwent a Miles' operation, total
      hysterectomy, resection of vagina, and thigh flap to vulva for rectal cancer.
      Before general anesthesia, an epidural catheter was inserted at T11-12
      interspace, and 1.5% mepivacaine 7ml was administered. Sensory block level spread
      from T4 to L1. Anesthesia was induced with propofol and maintained with
      sevoflurane in air oxygen mixture. Operation was performed uneventfully. After
      the operation, postoperative analgesia was achieved with patient-controlled
      epidural analgesia (PCEA). The epidural solution of 0.06% ropivacaine with 4
      microg x ml(-1) fentanyl and 20 microg x ml(-1) was connected to a PCA pump (i
      Fuser, JMS, Japan) that was programmed as an 8 ml initial bolus, 4 ml x hr(-1)
      basal infusion, 2 ml bolus dose, and 10-min lockout interval. Although abdominal
      pain was well controlled by PCEA, intractable pain in the pelvic nerve region
      existed. Patient-controlled intravenous analgesia (IV-PCA) with fentanyl,
      ketamine, and lidocaine was added to PCEA. Then excellent pain relief was
      obtained without any side effects such as nausea, vomiting, drowsiness, and
      respiratory depression. It could be useful to use IV-PCA together with PCEA when
      wide spread postoperative analgesia is necessary.

PMID- 21861423
TI  - [Anesthetic management of a patient with Becker muscular dystrophy].
AB  - We experienced anesthetic management of a patient with Becker muscular dystrophy.
      He had advanced dilated cardiomyopathy and high serum CK in the preoperative
      examinations. Anesthesia was planned to avoid triggering malignant hyperthermia
      or rhabdomyolysis and hemodynamic changes. Propofol, remifentanil and a minimum
      dose of rocuronium bromide were used for anesthetic induction and maintainance.
      Arterial pressure, cardiac output and stroke volume variation were monitored by
      Flotrac sensor. There were no adverse events observed during the anesthetic
      management. In conclusion, total intravenous anesthesia with the administration
      of rocuronium and circulatory monitoring by Flotrac sensor could be safe and
      efficient for anesthetic management of patients with Becker muscular dystrophy.

PMID- 21861424
TI  - [Case report: removing the press through package (PTP) containing a tablet from
      the subglottic region].
AB  - A 58-year-old female patient was prescribed different drugs in both tablet and
      powder form and inadvertently ingested the tablet along with its press through
      package (PTP), which thus became lodged in the subglottic region. An emergency
      operation was then performed to remove this foreign material, under neuroleptic
      anesthesia, and the foreign material was removed successfully. Furthermore, no
      abnormal findings, such as enlarged vocal cords, were noted. Vocal cord granuloma
      developed three months after the operation but it improved after conservative
      treatment.

PMID- 21861425
TI  - [Case of Takotsubo cardiomyopathy after induction of general anesthesia].
AB  - Takotsubo cardiomyopathy is a cardiac syndrome characterized by transient left
      ventricular dysfunction. A 79-year-old woman was scheduled for posterior lumbar
      interbody fusion for spinal compression fracture. After induction of general
      anesthesia, her blood pressure collapsed with significant ST rise in I, aVL, V3
      V5. Emergent transthoracic echocardiography revealed excessive contraction of the
      base and severe hypokinesis of the apex suggesting Takotsubo cardiomyopathy.
      Chronic hypovolemia and electrolyte disorder due to habitual glycerin enema were
      considered to be causes of this sudden cardiac collapse.

PMID- 21861426
TI  - [Total intravenous anesthesia for a patient with mitochondrial encephalomyopathy
      who underwent laparoscopic cholecystotomy].
AB  - A 49-year-old female with mitochondrial encephalomyopathy underwent laparoscopic
      cholecystotomy. She had some characteristic clinical symptoms, including muscle
      weakness, deafness, hemianopia and elevation of lactic acid level in the blood.
      It has been considered that problems of anesthesia for patient with mitochondrial
      encephalomyopathy are relevant to malignant hyperthermia, respiratory depression
      due to muscle weakness and probability of hyperlactacidemia. Anesthesia was
      induced with propofol, remifentanil and rocuronium, and maintained with
      continuous infusion of propofol and remifentanil, with administration of
      rocuronium under neuromuscular monitoring throughout the surgery. Arterial blood
      gases and pH were checked and acetated electrolyte solution was infused mainly
      during surgery. No complications occurred during anesthesia and this patient
      showed smooth recovery from anesthesia. Her postoperative course was uneventful.

PMID- 21861427
TI  - [Femoral and sciatic nerve blocks for open reduction and internal fixation of a
      femoral condylar fracture in a patient with post-polio syndrome].
AB  - The post polio symdrome (PPS) refers to the development of delayed neuromuscular
      symptoms among survivors, years after the initial presentation of acute
      poliomyelitis. The symptoms of PPS vary widely and include flaccid palsy, muscle
      weakness, scoliosis, osteoarthritis, gait disturbance, sleep apnea syndrome
      (SAS), dysphagia, chronic lung dysfunction, and others. We report the successful
      combination of peripheral nerve blocks, femoral and sciatic nerve blocks, for
      surgery on the lower extremity in a patient with PPS. A 51-year-old man with
      continuous positive airway pressure therapy for restrictive ventilatory
      impairment due to scoliosis and SAS as part of the PPS was scheduled for open
      reduction and internal fixation (OR-IF) for a right femoral condylar fracture.
      Respiratory function tests demonstrated a vital capacity (VC) 1.41l (41%
      predicted). Arterial blood gas analysis on room air was; pH 7.376, PaCO2 55.0
      mmHg, and PaO2 77.9 mmHg. With the patient in the supine position, ultrasound
      guided right femoral nerve block in the infra-inguinal region was performed using
      1.5% mepivacaine 10 ml and 0.75% ropivacaine 5 ml, followed by sciatic nerve
      block in the popliteal fossa using 1.5% mepivacaine 8 ml and 0.75% ropivacaine 4
      ml in the prone position. OR-IF of the fractured femoral condyle was then
      successfully performed with propofol under spontaneous ventilation.
      Postoperatively, there were no adverse events; respiratory function was adequate,
      and his pain was within manageable bounds. Femoral and sciatic nerve blocks are
      safe and effective anesthetic methods for lower extremity surgery in patients
      with restrictive ventilatory impairment and hypercapnia due to scoliosis and SAS
      as PPS.

PMID- 21861428
TI  - [Recovery from rocuronium by sugammadex does not affect motor evoked potentials].
AB  - Motor evoked potential (MEP) monitoring has been employed to detect the spinal
      cord injury during spinal, neurosurgical and cardiovascular operations. Muscle
      relaxants diminish the amplitude of MEP because MEP is the picture of
      electromyogram. In 5 cases undergoing MEP monitoring, we examined the effect of
      rocuronium followed by the administration of sugammadex on MEP Anesthesia was
      induced with propofol (target controlled infusion 3.0-3.5 microg x ml(-1)) and
      remifentanil 0.15-0.3 microg x kg(-1) x min(-1), and the trachea was intubated
      with the use of rocuronium 0.6 mg x kg(-1) without any muscle rigidity, bucking
      and laryngospasm. General anesthesia was maintained by total intravenous
      anesthesia using propofol and remifentanil with no muscle relaxants. Immediately
      after the tracheal intubation, sugammadex 4 mg x kg(-1) was intravenously given.
      The amplitude of MEP was measured just before the administration of rocuronium,
      immediately after the tracheal intubation, and 1, 2, 3, 5 min following the
      administration of sugammadex. Sugammadex restored the MEP amplitude, deteriorated
      by rocuronium, in 3 to 5 min to the level of non-paralytic muscles. In one case,
      it took 8 min to restore the MEP of hemiparetic leg. Taking these findings into
      consideration, it is likely that rocuronium might not affect the MEP when
      reversed by sugammadex, and should be safe for smooth tracheal intubation in
      patients who need MEP monitoring.

PMID- 21861430
TI  - [Anesthesia for nephrectomy in a functional hemirenal patient].
AB  - A 79-year-old woman was scheduled for resection of right renal cell carcinoma.
      She was a functional hemire-nal patient because of atrophy of the left kidney. To
      prevent overhydration, we maintained CVP at 4-6 cmH2O and SVV at 20-30% with
      FloTrac System during the surgery. As the result, urgent postoperative
      hemodialysis was successfully avoided.

PMID- 21861429
TI  - [Case with postoperative acute angle-closure glaucoma].
AB  - A 59-year-old man who had undergone biopsy of cervical lymph node under general
      anesthesia developed an attack of acute angle-closure glaucoma the night after
      the surgery. He had had no eye symptoms before. He complained of visual disorder,
      nausea, eye pain, and dizziness after the surgery. His intraocular pressure in
      the right eye was high (69 mmHg), and an ophthalmologist diagnosed it as acute
      angle-closure glaucoma. Dropping lotion in the eyes and the intravenous
      administration were not effective. His intraocular pressure decreased immediatery
      after laser iridotomy, and his symptoms improved. When the symptoms of eye pain
      and visual impairment appeared after the surgery, we should take acute angle
      closure glaucoma into consideration and treat it as soon as possible.

PMID- 21861431
TI  - [Excessive bleeding in the patients with past history of Hassab's operation].
AB  - We report two cases of massive perioperative bleeding and multiple organ failure
      with past history of Hassab's operation. Massive bleeding occurred during
      laparotomy and thoracocentesis in each case. After Hassab's operation, collateral
      circulation and coagulation disorders could develop, and unanticipated massive
      bleeding might occur. Preparations for excessive bleeding and postoperative
      intensive care would be required for the patients who have past history of
      Hassab's operation.

PMID- 21861432
TI  - [Comparative study of oral tracheal tube extubation force in a baby manikin
      model: taping methods and tube diameters].
AB  - BACKGROUND: Adhesive tape is the standard method for securing tracheal tubes.
      There have been several studies about extubation forces in adult models. However,
      there have been few in pediatric models. Therefore, we examined the force
      required to extubate tracheal tube from a manikin using three methods. METHODS: A
      baby simulation manikin was orally intubated. The tracheal tube (3.0 to 4.5 mm
      internal diameter) was fixed at the right oral corner. The tracheal tube was
      secured with adhesive tape with three different methods as follows: 1) 0.63 cm
      wide tape coiled around the tube twice, 2) 1.25 cm-wide tape coiled around the
      tube twice, 3) 1.25 cm-wide tape coiled up three times around the tube ("puttee
      style"). Adhesive tape was attached 10 cm on both sides of the tube along the
      lips. The tracheal tube was connected to a force-measuring device and pulled
      vertically until the tube was displaced 1 cm distally from the initial position.
      The required force was defined as the "extubation force". Each method was
      repeated 5 times. RESULTS: The extubation force was larger when the tape used was
      wider, and the contact area between the tracheal tube and tape was larger. The
      force was also larger as the tube diameter became larger. CONCLUSIONS: To fix a
      tracheal tube securely, adhesive tape should be wider and the contact area
      between the tube and the tape should be larger. In this regard, "puttee style"
      fixation seems to be effective.

PMID- 21861433
TI  - [Application of three compartment model and response surface model to clinical
      anesthesia using Microsoft Excel].
AB  - With the spread of total intravenous anesthesia, clinical pharmacology has become
      more important. We report Microsoft Excel file applying three compartment model
      and response surface model to clinical anesthesia. On the Microsoft Excel sheet,
      propofol, remifentanil and fentanyl effect-site concentrations are predicted
      (three compartment model), and probabilities of no response to prodding, shaking,
      surrogates of painful stimuli and laryngoscopy are calculated using predicted
      effect-site drug concentration. Time-dependent changes in these calculated values
      are shown graphically. Recent development in anesthetic drug interaction studies
      are remarkable, and its application to clinical anesthesia with this Excel file
      is simple and helpful for clinical anesthesia.

PMID- 21861434
TI  - [Experience of participating in the 14th Nepal Cleft Lip and Palate Surgery
      Project].
AB  - Adventist Development and Relief Agency (ADRA) Japan, a non governmental
      organization (NGO), following an official request of Federal Democratic Republic
      of Nepal Government has organized Nepal Cleft Lip and Palate Surgery Project
      since 1995. We participated in the 14th Project as one of the anesthesiologists
      from 7th to 22nd November 2009 and performed general anesthesia with a Nepalese
      anesthetist without a medical license in Sheer Memorial Hospital. Use of
      unfamiliar anesthetic medications and limited medical devices made us understand
      the difficulty of anesthetic management. This valuable anesthetic experience will
      be useful for us in general anesthetic management in the future.

PMID- 21861435
TI  - [Chronic fungal infection, up-to-date].
AB  - Deep-seated mycosis usually occurred in severe immunocompromised patients and is
      sometimes fatal. Hence, chronic fungal infection occurred in the patients with
      mild to moderate immunocompromised status and persists for longer period. Biofilm
      formation is one of the factors related to persisting infection of Candida spp.
      Biofilm formation resists to the antifungals in catheter-related Candida
      infection and selection of appropriate antifungals will be an important key to
      achieve good outcome. Although azoles possessed excellent antifungal activity
      against planktonic Candida spp., they show lower activity against biofilm-formed
      Candida spp. Overexpression of efflux pump of Candida spp. is reported to be
      involved in lowered activity of azoles. Amphotericin B, liposomal amphotericin B,
      and micafungin however, are expected to have high antifungal activity against
      biofilm-formed Candida spp. Recently, Aspergillus is also reported to possess
      potential of forming biofilm. Biofilm formation of Aspergillus is considered to
      be related to pathogenesis of chronic pulmonary aspergillosis. General
      antifungals are not highly active to biofilm-formed Aspergillus as same as
      Candida, and only amphotericin B and its liposomal formulation are expected to be
      effective in vitro.

PMID- 21861436
TI  - [Acinetobacter spp. infections].
AB  - Acinetobacter, which is Gram-negative non-fermentated bacilli, is isolated from
      natural environment and human body, including skin and gastrointestional tracts
      of both healthy persons and immunocompromised patients. Acinetobacter can cause
      bacterial infections, such as blood stream infections and health care-associated
      pneumonia. The definition of multi-drug resistant (MDR) of Acinetobacter has not
      been internationally harmonized, however, it is defined when MICs of imipenem,
      amikacin and ciprofloxacin are 16 microg/ml, 32 microg/ml and 4 microg/ml or
      higher, respectively, in Japan. Recently, only a few outbreaks by Acinetobacter
      have been reported in Japan, while outbreaks by Acinetobacter are more common in
      Western and Asian countries abroad. We should pay attention and caution on
      outbreaks by Acinetobacter and spread of drug-resistant Acinetobacter as much as
      we can.

PMID- 21861437
TI  - [Analysis of extended-spectrum CTX-M-14 beta-lactamase (ESBLs) producing
      Escherichia coli isolates in the same ward over the long term].
AB  - We bacteriologically and genetically analysed 30 cephalosporin-resistant
      Escherichia coli strains isolated from specimens from 19 neurology-ward
      inpatients at our hospital over the 3 years from April 2006 to March 2009,
      surveying and comparing subjects' backgrounds. Of the 30, 19 (63%) were urine, 6
      (20%) sputum, and 3 (10%) blood. We tested extended-spectrum beta-lactamase
      (ESBLs) production, found in all samples. PCR and gene sequencing showed that 25
      strains (83%) were CTX-M-14 and 5 (17%) CTX-M-2. Among CTX-M-14 strains, two
      cluster groups I and II, were obtained using pulsed-field gel electrophoresis
      (PFGE). Cluster group I in particular, continued to be detected for 18 months in
      the same hospital room. The detection rate was high at 13 (68%) in subjects with
      urinary catheters and morbidity was high in those with a history of
      cerebrovascular disease, diabetes, and hypertension. Our findings suggest that
      genetically identical strains may become established and spread in hospitals
      possibly due to inadequate contact prevention, subjects' immune status, and risk
      factor existence.

PMID- 21861438
TI  - [Surveillance of nalidixic acid-resistant and extended-spectrum beta-lactamase
      producing Salmonella spp. isolated from human feces].
AB  - Nalidixic acid (NA)-resistant and extended-spectrum beta-lactamase (ESBL)
      producing Salmonella sp. isolates from human specimens are associated with
      clinical failure or delayed response in subjects treated with fluoroquinolone or
      third-generation cephalosporins. We studied drug susceptibility in 604 Salmonella
      enterica isolates from human feces in 2007. Of these, 39 (6.5%) were resistat to
      NA. Of these, 46% were resistant to two or more drugs and 2% susceptible to NA
      were resistant to multiple drugs (p < 0.001). Three ESBL-producing Salmonella sp.
      isolated were of the CTX-M family gene type. One strain of plasmid-mediated AmpC
      beta-lactamase belonged to the CMY-2 family gene type. Our results thus showed
      that NA-resistant isolates were resistant to antimicrobial agents and confirmed
      the presence of a small number of isolates producing ESBL and AmpC beta
      lactamase.

PMID- 21861439
TI  - [Nationwide antimicrobial susceptibility survey of Neisseria gonorrhoeae isolates
      in Japan].
AB  - In a nationwide antimicrobial susceptibility survey of 494 Nesseria gonorrhoeae
      isolates collected from February 2008 to December 2009 in 3 regions of Japan, 112
      (22.7%) were collected from western Japan (Kinki, Chugoku, Shikoku, and Kyushu),
      277 (56.1%) from mid-eastern Japan (Kanto), and 105 (21.1%) from eastern Japan
      (Tokai, Hokuriku, Koushinetsu, Tohoku, and Hokkaido). Resistance to ciprofloxacin
      (CPFX) was 72.8%, to penicillin G (PCG) 19.8%, and to tetracycline (TC) 18.2%.
      Intermediate resistance to CPFX was 1.8%, to PCG 73.7%, and to TC 43.7%. These
      results indicate that both types of resistance to the 3 agents were very high.
      Intermediate resistance to cefixime (CFIX) was 38.1% and to cefozidim (CDZM)
      13.4%. Resistance to CFIX was only 0.4% and to CDZM 0%. Susceptibility to
      azithromycin was 96.6%, to ceftriaxone 99.8%, and to spectinomycin 100%. No
      significant difference in resistance was seen to different antimicrobial agent
      classes tested in the 3 regions, although intermediate resistance to CFIX in
      western Japan was significantly higher than in mid-eastern Japan.

PMID- 21861440
TI  - [Severe primary liver abscess and septic pulmonary embolism due to Klebsiella
      pneumoniae with hypermucoviscosity phenotype].
AB  - A 70-year-old man with diabetes mellitus seen for fever, right chest pain, and
      right-lung field consolidation on chest X-ray was found in thoracoabdominal
      computed tomography (CT) to have variable-sized nodules in both lung fields and
      multiple low-density hepatic areas. On physical examination, his pulse was 145
      beats per minute and blood pressure 92/68mmHg, indicating a preshock state.
      Laboratory tests showed elevated WBC of 15,200/microL, serum-C-reactive protein
      (CRP) of 34.4 mg/dL, and a decreased platelet count of 16,000/microL. Suspecting
      liver abscesses complicated by a septic pulmonary embolism, we immediately
      conducted percutaneous transhepatic abscess drainage (PTAD). Liver abscess blood
      culture and drainage fluid grew the Klebsiella pneumoniae hypermucoviscosity
      phenotype, carrying the rmpA gene. Although the man had been in critical
      condition on admission, broad-spectrum antibiotics and PTAD treatment improved
      his clinical condition to where he could be discharged without problem.

PMID- 21861441
TI  - [A case of disseminated gonococcal infection without typical skin rash].
AB  - Few case reports have been published on disseminated gonococcal infection in
      Japan. We report such a non-HIV case without typical skin rash. A 49-year-old
      Japanese man living in Thailand on business was seen for fever and multiple
      arthralgia after returning to Japan. Given the travel history, differential
      diagnoses included endemic viral infection such as human immunodeficiency virus
      (HIV), dengue fever, and chikungunya. Diagnosis was based on right-knee
      arthrocentesis, and synovial fluid culture followed by Neisseria gonorrhoeae
      polymerase chain reaction (PCR). The isolated strain was sensitive to penicillin.
      The man was treated with intravenous ceftriaxone and oral levofloxacin.
      Disseminated gonococcal infection should thus be considered when examining those
      with classical polyarthralgia symptoms even without a typical skin rash.

PMID- 21861442
TI  - [Four cases of respiratory infections caused by Legionella pneumophila serogroup
      3].
AB  - Legionella pneumonia tends to be severe and is known to be fatal. Introduction of
      the urinary Legionella antigen test and changes in the Infectious Disease Law
      have led to increased numbers of reports, and milder cases are now occasionally
      seen. We experienced three cases demonstrating mild respiratory infections and
      one case demonstrating nosocomial pneumonia associated by Legionella pneumophila
      serogroup 3. Case 1 showed multiple ground-glass opacities on HRCT and productive
      cough. Cases 2 and 3 showed abnormal findings on chest X-ray, and chest CT
      findings in both cases suggested chronic respiratory infection. Case 4
      experienced fever and hypoxia, and pulmonary edema was noted on X-ray. All of
      them four cases were diagnosed with respiratory infections isolated L.
      pneumophila serogroup 3 by culture results, and three of them cases were treated
      in the outpatient clinic. Thus, milder cases of Legionella pneumonia may be
      encountered during routine care, and tests for Legionella should be performed in
      such cases.

PMID- 21861443
TI  - [A case of pneumonia due to Enterococcus faecium after near drowing].
AB  - A 73-year-old man admitted for near drowning was found after 24 hours of mild
      therapeutic hypothermia to have pneumonia. Blood gas analysis showed metabolic
      acidosis, hypercapnia, and hyponatremia. Chest X-ray and computed tomography (CT)
      showed bilateral mainly lower-lobe consolidation. After being treated with 13.5 g
      of tazobactam/piperacillin and 1.0-1.25 g of vancomycin per day for two weeks,
      the man recovered from his severe respiratory failure. Enterococcus faecium was
      isolated twice from sputum and raising the dose of vancomycin was effective, but
      it took 10 days to wean him from ventilator support. While this case may be rare,
      therapeutic hypothermia and near drowning together were considered predisposing
      factors in the severity of the pneumonia caused by E. faecium. The possibility of
      pneumonia due to vancomycin-resistant Enterococci should thus be considered in
      similar cases.

PMID- 21861444
TI  - [Correlation between osteoporosis and atherosclerosis in those with HIV
      infection].

PMID- 21861445
TI  - [Shifts in minimum inhibitory concentration of linezolid to Stapylococcus aureus
      strains isolated from 2007 to 2009].

PMID- 21861446
TI  - Electrochemical, spectroscopic, and photophysical properties of structurally
      diverse polyazine-bridged Ru(II),Pt(II) and Os(II),Ru(II),Pt(II) supramolecular
      motifs.
AB  - Five new tetrametallic supramolecules of the motif
      [{(TL)(2)M(dpp)}(2)Ru(BL)PtCl(2)](6+) and three new trimetallic light absorbers
      [{(TL)(2)M(dpp)}(2)Ru(BL)](6+) (TL = bpy = 2,2'-bipyridine or phen = 1,10
      phenanthroline; M = Ru(II) or Os(II); BL = dpp = 2,3-bis(2-pyridyl)pyrazine, dpq
      = 2,3-bis(2-pyridyl)quinoxaline, or bpm = 2,2'-bipyrimidine) were synthesized and
      their redox, spectroscopic, and photophysical properties investigated. The
      tetrametallic complexes couple a Pt(II)-based reactive metal center to Ru and/or
      Os light absorbers through two different polyazine BL to provide structural
      diversity and interesting resultant properties. The redox potential of the
      M(II/III) couple is modulated by M variation, with the terminal Ru(II/III)
      occurring at 1.58-1.61 V and terminal Os(II/III) couples at 1.07-1.18 V versus
      Ag/AgCl. [{(TL)(2)M(dpp)}(2)Ru(BL)](PF(6))(6) display terminal M(dpi)-based
      highest occupied molecular orbitals (HOMOs) with the dpp(pi*)-based lowest
      unoccupied molecular orbital (LUMO) energy relatively unaffected by the nature of
      BL. The coupling of Pt to the BL results in orbital inversion with localization
      of the LUMO on the remote BL in the tetrametallic complexes, providing a lowest
      energy charge separated (CS) state with an oxidized terminal Ru or Os and
      spatially separated reduced BL. The complexes [{(TL)(2)M(dpp)}(2)Ru(BL)](6+) and
      [{(TL)(2)M(dpp)}(2)Ru(BL)PtCl(2)](6+) efficiently absorb light throughout the UV
      and visible regions with intense metal-to-ligand charge transfer (MLCT)
      transitions in the visible at about 540 nm (M = Ru) and 560 nm (M = Os) (epsilon
      ~ 33,000-42,000 M(-1) cm(-1)) and direct excitation to the spin-forbidden (3)MLCT
      excited state in the Os complexes about 720 nm. All the trimetallic and
      tetrametallic Ru-based supramolecular systems emit from the terminal Ru(dpi)
      >dpp(pi*) (3)MLCT state, lambda(max)(em) ~ 750 nm. The tetrametallic systems
      display complex excited state dynamics with quenching of the (3)MLCT emission at
      room temperature to populate the lowest-lying (3)CS state population of the
      emissive (3)MLCT state.

PMID- 21861447
TI  - Unprecedented luminescent heteropolynuclear aggregates with gold thiolates as
      building blocks.
AB  - The reaction of [AuCl(P-N)], in which P-N represents a heterofunctional phosphine
      ligand, with pentafluorothiophenol, HSC(6)F(5), gives the thiolate gold
      derivatives [Au(SC(6)F(5))(P-N)] (P-N = PPh(2)py (1), PPh(2)CH(2)CH(2)py (2), or
      PPhpy(2) (3)). Complex [Au(SC(6)F(5))(PPh(2)py)] (1) reacts with
      [Au(OTf)(PPh(2)py)] in a 1:1 or 1:2 molar ratio to afford the di- or trinuclear
      species [Au(2)(MU-SC(6)F(5))(PPh(2)py)(2)]OTf (4) and [Au(3)(MU(3)
      SC(6)F(5))(PPh(2)py)(3)](OTf)(2) (5), with the thiolate acting as a doubly or
      triply bridging ligand. The reactivity of the mononuclear compounds
      [Au(SC(6)F(5))(P-N)] toward silver or copper salts in different ratios has been
      investigated. Thus, the treatment of [Au(SC(6)F(5))(P-N)] with Ag(OTf) or
      [Cu(NCMe)(4)]PF(6) in a 1:1 molar ratio gives complexes of stoichiometry
      [AuAg(OTf)(MU-SC(6)F(5))(P-N)] (P-N = PPh(2)py (6), PPh(2)CH(2)CH(2)py (7), or
      PPhpy(2) (8)) or [AuCu(MU-SC(6)F(5))(P-N)(NCMe)]PF(6) (P-N = PPh(2)py (9),
      PPh(2)CH(2)CH(2)py (10), or PPhpy(2) (11)). These complexes crystallize as dimers
      and display different coordination modes of the silver or copper center,
      depending on the present functionalized phosphine ligand. The treatment of
      [Au(SC(6)F(5))(PPh(2)py)] with silver and copper compounds in other molar ratios
      has been carried out. In a 2:1 ratio, the complexes [Au(2)M(MU-SC(6)F(5))(2)(MU
      PPh(2)py)(2)]X (M = Ag, X = OTf (12); M = Cu, X = PF(6) (13)) are obtained. The
      same reaction in a 4:3 molar ratio affords the species [Au(4)M(2)(MU
      SC(6)F(5))(3)(MU-PPh(2)py)(4)]X(3) (M = Ag, X = OTf (14); M = Cu, X = PF(6)
      (15)). The crystal structures of some of these complexes reveal different
      interactions among the metallic d(10) centers. The complexes display dual
      emission. The band at higher energy has been attributed to intraligand (IL)
      transitions, and the one at lower energy has been assigned to a ligand to metal
      (LM) charge transfer process. The latter emission is modulated by the heterometal
      (silver or copper).

PMID- 21861448
TI  - Two metals are better than one in the gold catalyzed oxidative heteroarylation of
      alkenes.
AB  - We present a detailed study of the mechanism for oxidative heteroarylation, based
      on DFT calculations and experimental observations. We propose binuclear Au(II)
      Au(II) complexes to be key intermediates in the mechanism for gold catalyzed
      oxidative heteroarylation. The reaction is thought to proceed via a gold redox
      cycle involving initial oxidation of Au(I) to binuclear Au(II)-Au(II) complexes
      by Selectfluor, followed by heteroauration and reductive elimination. While it is
      tempting to invoke a transmetalation/reductive elimination mechanism similar to
      that proposed for other transition metal complexes, experimental and DFT studies
      suggest that the key C-C bond forming reaction occurs via a bimolecular reductive
      elimination process (devoid of transmetalation). In addition, the stereochemistry
      of the elimination step was determined experimentally to proceed with complete
      retention. Ligand and halide effects played an important role in the development
      and optimization of the catalyst; our data provides an explanation for the ligand
      effects observed experimentally, useful for future catalyst development. Cyclic
      voltammetry data is presented that supports redox synergy of the Au...Au
      aurophilic interaction. The monometallic reductive elimination from mononuclear
      Au(III) complexes is also studied from which we can predict a ~15 kcal/mol
      advantage for bimetallic reductive elimination.

PMID- 21861449
TI  - Container effect in nanocasting synthesis of mesoporous metal oxides.
AB  - We report a general reaction container effect in the nanocasting synthesis of
      mesoporous metal oxides. The size and shape of the container body in conjunction
      with simply modifying the container opening accessibility can be used to control
      the escape rate of water and other gas-phase byproducts in the calcination
      process, and subsequently affect the nanocrystal growth of the materials inside
      the mesopore space of the template. In this way, the particle size, mesostructure
      ordering, and crystallinity of the final product can be systemically controlled.
      The container effect also explain some of the problems with reproducibility in
      previously reported results.

PMID- 21861450
TI  - Free radical lipid peroxidation: mechanisms and analysis.

PMID- 21861451
TI  - A new type of bis(sulfonamide)-diamine ligand for a Cu(OTf)2-catalyzed asymmetric
      Friedel-Crafts alkylation reaction of indoles with nitroalkenes.
AB  - Chiral bis(sulfonamide)-diamine served as new type of ligand for a Cu(OTf)(2)
      catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with
      nitroalkenes. The desired products were obtained with up to 99% yield and 97% ee.

PMID- 21861452
TI  - A new strategy for the synthesis of bisaminoacylated tRNAs.
AB  - Tandemly activated tRNAs participate effectively in protein synthesis and exhibit
      superior chemical and biochemical stability compared to the more commonly used
      singly aminoacylated tRNAs. While several bisaminoacylated tRNAs have been
      prepared via the T4 RNA ligase-mediated condensation of bisaminoacylated pdCpAs
      and abbreviated tRNA transcripts (tRNA-C(OH)), the bisaminoacylated pdCpAs are
      difficult to prepare when using bulky amino acids. Described herein is a new
      strategy for preparing bisaminoacylated tRNAs, applicable even for bulky amino
      acids.

PMID- 21861453
TI  - Cu(II)-catalyzed intermolecular amidation of C-acylimine: a convenient access to
      gem-diamino acid derivatives.
AB  - C-Acylimines 1 undergo intermolecular amidation with amides 2 to produce monoacyl
      gem-diamino acid derivatives 3 upon treatment with Cu(OTf)(2) (20 mol%)/ PPh(3)
      (20 mol%) under mild conditions. This method provides an efficient access to gem
      diamino acid equivalents with good to excellent yields.

PMID- 21861455
TI  - Chiral counteranion synergistic organocatalysis under high temperature: efficient
      construction of optically pure spiro[cyclohexanone-oxindole] backbone.
AB  - The combination of a cinchona-based chiral primary amine and a BINOL-phosphoric
      acid has been demonstrated as a powerful and synergistic catalyst system for the
      double Michael addition of isatylidene malononitriles with alpha,beta-unsaturated
      ketones, to provide the novel chiral spiro [cyclohexane-1,3'-indoline]-2',3
      diones in high yields (88-99%) with excellent diastereo- and enantioselectivities
      (94:6-99:1 dr's, 95-99% ee's).

PMID- 21861456
TI  - Isolation of a metastable geometrical isomer of a hexacoordinated
      dihydrophosphate: elucidation of its enhanced reactivity in umpolung of a
      hydrogen atom of water.
AB  - Two of five conceivable geometrical isomers of a hexacoordinated dihydrophosphate
      bearing two sets of a bidentate ligand were investigated. X-ray crystallographic
      analysis of both of isomers, 1a-TPP and 1b-TEA, revealed their octahedral
      geometries of C(2) and C(1) symmetry, respectively, which were consistent with
      the NMR spectra. The isomer 1b-TEA underwent both hydride reduction of an
      aldehyde and proton exchange with water at room temperature in DMSO without any
      additive. A one-pot reaction of both of the reactions of 1b-TEA with D(2)O and an
      aldehyde or a ketone under the above conditions proceeded successfully to give
      the deuterated alcohol. Thus, umpolung of a hydrogen atom of water with 1b-TEA
      was achieved under much milder conditions than those used in the reaction with
      another isomer, 1a-TEA. Quantitative isomerization of 1b-TEA to 1a-TEA occurred
      in methanol at room temperature. Calculations on the five conceivable geometrical
      isomers of the anionic part of the dihydrophosphate revealed their relative
      stability, which reasonably explained the isomerization, and the larger negative
      charge at the atoms located at the trans positions of the oxygen atoms. The
      smaller coupling constants of the P-H and P-C bonds located at the rear of an
      oxygen atom in the NMR spectra resulted in the smaller s character of these
      bonds. The differences in both hydride-donation and proton-exchange reactivities
      between 1a-TEA and 1b-TEA could be explained by the differences in the atomic
      charge of the hydrogen atom and the stability difference of the initially formed
      phosphorane intermediates, respectively.

PMID- 21861454
TI  - Epitope mapping of a 95 kDa antigen in complex with antibody by solution-phase
      amide backbone hydrogen/deuterium exchange monitored by Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - The epitopes of a homohexameric food allergen protein, cashew Ana o 2, identified
      by two monoclonal antibodies, 2B5 and 1F5, were mapped by solution-phase amide
      backbone H/D exchange (HDX) coupled with Fourier transform ion cyclotron
      resonance mass spectrometry (FTICR MS) and the results were compared to previous
      mapping by immunological and mutational analyses. Antibody 2B5 defines a
      conformational epitope, and 1F5 defines a linear epitope. Intact murine IgG
      antibodies were incubated with recombinant Ana o 2 (rAna o 2) to form antigen
      monoclonal antibody (Ag-mAb) complexes. mAb-complexed and uncomplexed (free) rAna
      o 2 were then subjected to HDX. HDX instrumentation and automation were optimized
      to achieve high sequence coverage by protease XIII digestion. The regions
      protected from H/D exchange upon antibody binding overlap and thus confirm the
      previously identified epitope-bearing segments: the first extension of HDX
      monitored by mass spectrometry to a full-length antigen-antibody complex in
      solution.

PMID- 21861457
TI  - Detection of DNA targets hybridized to solid surfaces using optical images of
      liquid crystals.
AB  - In this paper, we report a method of detecting DNA targets hybridized to a solid
      surface by using liquid crystals (LC). The detection principle is based on
      different interference colors of LC supported on surfaces decorated with single
      stranded DNA (ssDNA) or double-stranded DNA (dsDNA). However, the contrast
      between the ssDNA and dsDNA is not obvious, unless DNA-streptavidin complexes are
      introduced to the dsDNA to increase the surface mass density. Two different
      approaches of introducing streptavidin to the system are studied and compared. We
      find that by premixing the biotin-labeled DNA targets with streptavidin prior to
      the DNA hybridization, branched-streptavidin complexes are formed and clear LC
      signal can be observed. This LC-based DNA detection principle represents an
      important step toward the development of a simple, instrument- and fluorophore
      free DNA detection method.

PMID- 21861458
TI  - Quercetin and kaempferol 3-O-[alpha-L-rhamnopyranosyl-(1->2)-alpha-L
      arabinopyranoside]-7-O-alpha-L-rhamnopyranosides from Anthyllis hermanniae:
      structure determination and conformational studies.
AB  - The study reports the isolation and structural identification of two new flavonol
      triglycosides from the methanolic extract of Anthyllis hermanniae, exhibiting the
      same glycosylation pattern: quercetin 3-O-[alpha-L-rhamnopyranosyl-(1->2)-alpha-L
      arabinopyranoside]-7-O-alpha-L-rhamnopyranoside (1) and kaempferol 3-O-[alpha-L
      rhamnopyranosyl-(1->2)-alpha-L-arabinopyranoside]-7-O-alpha-L-rhamnopyranoside
      (2). A conformational study related to the central arabinoside moiety was carried
      out including the analysis of the contribution of NOE effects and acetylation to
      the elucidation of the 2-O-linked arabinoside configuration of the anomeric
      carbon. We also report the total synthesis of a model compound, quercetin 3-O
      alpha-L-rhamnopyranosyl-(1->2)-alpha-L-arabinopyranoside (3), which verifies the
      structures of the isolated compounds.

PMID- 21861460
TI  - Noninvasive in vivo monitoring of the biofate of 195 kDa poly(vinyl alcohol) by
      multispectral fluorescence imaging.
AB  - A comprehensive knowledge of the in vivo fate of polymers is essential for their
      potential application in humans. In this study, the body distribution,
      accumulation, and elimination processes of intraperitoneally (ip) administered
      poly(vinyl alcohol) (PVA) in mice were investigated in detail. Two derivatives of
      PVA (195 kDa) having covalently bound fluorescent dye labels were synthesized and
      used to follow PVA in vivo by noninvasive multispectral fluorescence imaging over
      several months. Detailed ex vivo fluorescence imaging was performed additionally
      and combined with tissue accumulation studies using confocal microscopy.
      Filtration and confocal imaging at appropriate synthetic membranes, used as
      models for glomerular filtration, confirmed a considerable PVA permeation. This
      investigation yields new scientific findings about the fate of PVA in vivo. PVA
      accumulated in fat tissue at high levels, which suggests that PVA is suitable not
      only for abdominal surgeries but also for controlled release applications after
      ip or subcutaneous injection.

PMID- 21861459
TI  - Human defensin 5 disulfide array mutants: disulfide bond deletion attenuates
      antibacterial activity against Staphylococcus aureus.
AB  - Human alpha-defensin 5 (HD5, HD5(ox) to specify the oxidized and disulfide linked
      form) is a 32-residue cysteine-rich host-defense peptide, expressed and released
      by small intestinal Paneth cells, that exhibits antibacterial activity against a
      number of Gram-negative and -positive bacterial strains. To ascertain the
      contributions of its disulfide array to structure, antimicrobial activity, and
      proteolytic stability, a series of HD5 double mutant peptides where pairs of
      cysteine residues corresponding to native disulfide linkages (Cys(3)-Cys(31),
      Cys(5)-Cys(20), Cys(10)-Cys(30)) were mutated to Ser or Ala residues,
      overexpressed in E. coli, purified, and characterized. A hexa mutant peptide,
      HD5[Ser(hexa)], where all six native Cys residues are replaced by Ser residues,
      was also evaluated. Removal of a single native S-S linkage influences oxidative
      folding and regioisomerization, antibacterial activity, Gram-negative bacterial
      membrane permeabilization, and proteolytic stability. Whereas the majority of the
      HD5 mutant peptides show low micromolar activity against Gram-negative E. coli
      ATCC 25922 in colony counting assays, the wild-type disulfide array is essential
      for low micromolar activity against Gram-positive S. aureus ATCC 25923. Removal
      of a single disulfide bond attenuates the activity observed for HD5(ox) against
      this Gram-positive bacterial strain. This observation supports the notion that
      the HD5(ox) mechanism of antibacterial action differs for Gram-negative and Gram
      positive species [Wei et al. (2009) J. Biol. Chem. 284, 29180-29192] and that the
      native disulfide array is a requirement for its activity against S. aureus.

PMID- 21861461
TI  - Molecular-level engineering of protein physical hydrogels for predictive sol-gel
      phase behavior.
AB  - Predictable tuning of bulk mechanics from the molecular level remains elusive in
      many physical hydrogel systems because of the reliance on nonspecific and
      nonstoichiometric chain interactions for network formation. We describe a mixing
      induced two-component hydrogel (MITCH) system, in which network assembly is
      driven by specific and stoichiometric peptide-peptide binding interactions. By
      integrating protein science methodologies with a simple polymer physics model, we
      manipulate the polypeptide binding interactions and demonstrate the direct
      ability to predict the resulting effects on network cross-linking density, sol
      gel phase behavior, and gel mechanics.

PMID- 21861462
TI  - Ca L23 spectrum in amorphous and crystalline phases of calcium carbonate.
AB  - The calcium L(23) absorption edge is very sensitive to changes in local symmetry.
      Distinct spectra from calcite and aragonite as well as two different amorphous
      phases of calcium carbonate have been reported. Multiplet calculations using the
      CTM4XAS code, taking account of the local symmetry and the crystal field, suggest
      that the coordination octahedra are distorted by a change in length along one
      axis, the reduction in symmetry being coupled with tetrahedral displacements of
      the 4 atoms in the perpendicular plane. Examination of the polarization
      dependence implies that the two different amorphous phases arise from different
      levels of ordering of the oxygen coordination polyhedra around calcium. The
      change in the ordering suggests a pathway for the transformation to single
      crystal calcite. Although the code is unable to directly simulate the very low
      symmetry environment of Ca in aragonite, some degree of agreement is obtained
      with the same distortion of the coordination octahedron and greater tetrahedral
      displacements.

PMID- 21861463
TI  - Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)
      N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3
      dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides
      potent anticonvulsants with pain-attenuating properties.
AB  - Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides
      (primary amino acid derivatives (PAADs)) exhibited pronounced activities in
      established whole animal anticonvulsant (i.e., maximal electroshock seizure
      (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant
      activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21
      mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional
      studies defining the structure-activity relationship of PAADs are presented in
      this issue of the journal. In this study, we demonstrated that the anticonvulsant
      activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino
      3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide
      site; electron-withdrawing groups retained activity, electron-donating groups led
      to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3
      fluorophenoxymethyl group using a rationally designed multiple ligand approach
      improved activity. Additionally, we showed that substituents at the 4'-N'
      benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved
      anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the
      largest (~4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that
      surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological
      findings provided new information that C(2)-hydrocarbon PAADs represent a novel
      class of anticonvulsants.

PMID- 21861464
TI  - Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: ionic liquid based systems for
      aromatic nitration.
AB  - Acting as in situ sources of triflyl nitrate (TfONO(2)) and trifluoroacetyl
      nitrate (CF(3)COONO(2)), the EAN/Tf(2)O and EAN/TFAA systems, generated via
      metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as
      solvent, are powerful electrophilic nitrating reagents for a wide variety of
      aromatic and heteroaromatic compounds. Comparative nitration experiments indicate
      that EAN/Tf(2)O is superior to EAN/TFAA for nitration of strongly deactivated
      systems. Both systems exhibit low substrate selectivity (K(T)/K(B) = 5-10) in
      between values reported for covalent nitrates and preformed nitronium salts.

PMID- 21861465
TI  - Injectable polyHIPEs as high-porosity bone grafts.
AB  - Polymerization of high internal phase emulsions (polyHIPEs) is a relatively new
      method for the production of high-porosity scaffolds. The tunable architecture of
      these polyHIPE foams makes them attractive candidates for tissue engineered bone
      grafts. Previously studied polyHIPE systems require either toxic diluents or high
      cure temperatures which prohibit their use as an injectable bone graft. In
      contrast, we have developed an injectable polyHIPE that cures at physiological
      temperatures to a rigid, high-porosity foam. First, a biodegradable macromer,
      propylene fumarate dimethacrylate (PFDMA), was synthesized that has appropriate
      viscosity and hydrophobicity for emulsification. The process of surfactant
      selection is detailed with particular focus on the key structural features of
      both polymer (logP values, hydrogen bond acceptor sites) and surfactant (HLB
      values, hydrogen bond donor sites) that enable stable HIPE formation. Incubation
      of HIPEs at 37  degrees C was used to initiate radical cross-linking of the
      unsaturated double bond of the methacrylate groups to polymerize the continuous
      phase and lock in the emulsion geometry. The resulting polyHIPEs exhibited ~75%
      porosity, pore sizes ranging from 4 to 29 MUm, and an average compressive modulus
      and strength of 33 and 5 MPa, respectively. These findings highlight the great
      potential of these scaffolds as injectable, tissue engineered bone grafts.

PMID- 21861467
TI  - pH-Sensitive micelles with cross-linked cores formed from polyaspartamide
      derivatives for drug delivery.
AB  - A series of polyaspartamide derivatives were synthesized by grafting O-(2
      aminoethyl)-O'-methylpoly(ethylene glycol) 5000 (MPEG), 1-(3-aminopropyl)
      imidazole (API), and cinnamate onto polysuccinimide (PSI) with the respective
      degrees of substitution adjusted by the feed molar ratio. The chemical structure
      of the prepared polymer was confirmed using FT-IR and (1)H NMR spectroscopy. A
      new pH-sensitive polymeric micelle based on the synthesized polymer was prepared
      and characterized, and its pH-sensitive properties were characterized by the
      measurement of light transmittance and particle sizes at varying pH values. pH
      dependent aggregation and deaggregation behavior was clearly observed in the
      polymer aqueous dispersion system. Photo-cross-linking of the cinnamate branches
      cross-linked the core of the micelles. The core cross-linked micelles showed high
      stability over a wider pH range and displayed obvious pH-dependent swelling
      shrinking behavior instead of micelle-unimer transition behavior. This micelle
      system overcame the drawback of the facile disintegration of normal polymeric
      micelles and showed obvious delayed paclitaxel release in in vitro drug delivery
      experiments.

PMID- 21861466
TI  - Defining the structural parameters that confer anticonvulsant activity by the
      site-by-site modification of (R)-N'-benzyl 2-amino-3-methylbutanamide.
AB  - Primary amino acid derivatives (PAADs) (N'-benzyl 2-substituted 2-amino
      acetamides) are structurally related to functionalized amino acids (FAAs) (N'
      benzyl 2-substituted 2-acetamido acetamides) but differ by the absence of the
      terminal N-acetyl group. Both classes exhibit potent anticonvulsant activities in
      the maximal electroshock seizure animal model, and the reported structure
      activity relationships (SARs) of PAADs and FAAs differ in significant ways.
      Recently, we documented that PAAD efficacy was associated with a hydrocarbon
      moiety at the C(2)-carbon, while in the FAAs, a substituted heteroatom one atom
      removed from the C(2)-center was optimal. Previously in this issue, we showed
      that PAAD activity was dependent upon the electronic properties of the 4'-N'
      benzylamide substituent, while FAA activity was insensitive to electronic changes
      at this site. In this study, we prepared analogues of (R)-N'-benzyl 2-amino-3
      methylbutanamide to identify the structural components for maximal anticonvulsant
      activity. We demonstrated that the SAR of PAADs and FAAs diverged at the terminal
      amide site and that PAADs had considerably more structural latitude in the types
      of units that could be incorporated at this position, suggesting that these
      compounds function according to different mechanism(s).

PMID- 21861468
TI  - Active modulation of nanorod plasmons.
AB  - Confining visible light to nanoscale dimensions has become possible with surface
      plasmons. Many plasmonic elements have already been realized. Nanorods, for
      example, function as efficient optical antennas. However, active control of the
      plasmonic response remains a roadblock for building optical analogues of
      electronic circuits. We present a new approach to modulate the polarized
      scattering intensities of individual gold nanorods by 100% using liquid crystals
      with applied voltages as low as 4 V. This novel effect is based on the transition
      from a homogeneous to a twisted nematic phase of the liquid crystal covering the
      nanorods. With our method it will be possible to actively control optical
      antennas as well as other plasmonic elements.

PMID- 21861469
TI  - On the shock sensitivity of explosive compounds with small-scale gap test.
AB  - In this work an improved set of small-scale gap tests was applied to measure the
      shock sensitivity of 13 explosive compounds, and a Mn-Cu manometer was also
      employed to measure the output pressures of shock waves passed through aluminum
      gaps with different thicknesses to draw a standard curve. The critical initiation
      thicknesses of aluminum gaps of different explosive compounds (244 shots in
      total) were treated according to statistical method, and the Mulliken charges of
      nitro groups, bond dissociation energies of X-NO(2) (X = C, N), resonance
      energies, and ring strain energies of these explosive compounds were calculated
      with the means of DFT/BLYP/DNP calculations and homodesmotic reactions designs.
      Genetic function approximation was used to construct a relationship between the
      critical initiation thicknesses of aluminum gaps of different explosive compounds
      and their forementioned molecule structural parameters.

PMID- 21861470
TI  - Polyethylenimine containing benzimidazole branching: a model system providing a
      balance of hydrogen bond network or chain mobility enhances proton conductivity.
AB  - A series of multibenzimidazole functionalized branched polyethylenimine (MPEI)
      molecules with varied benzimidazole substitution are designed and synthesized to
      study how hydrogen bonds of benzimidazole can be enhanced through the branching
      structure of polymer chains. The reduction of H-bonding and the increment of
      interatomic distance distribution initiate an increase in proton conductivity
      with temperature as detailed analyses by temperature dependence Fourier transform
      infrared spectroscopy and radial distribution function calculated from
      temperature dependence X-ray diffraction technique. MPEIs with a higher
      benzimidazole substitution form a greater number of hydrogen bonds together with
      the lowering of chain mobility. In combination with the proton conductivity
      evaluation, bPEI with 19.7% benzimidazole substitution is a preferable condition
      since at this condition both hydrogen bond and chain mobility are in good balance
      and favor the proton transfer resulting in a significant proton conductivity ~10(
      5) S cm(-1) in the case of the pure sample in pellet form and ~10(-4) S cm(-1) in
      the case of the blend with PVA in the membrane form measuring at 190  degrees C
      under anhydrous condition.

PMID- 21861472
TI  - Phosphorylimidazole derivatives: potentially biosignaling molecules.
AB  - The phosphorylation of imidazole by two activated phosphate diesters and a
      triester gives phosphorylimidazole derivatives that are stable enough in aqueous
      solution to be observed and identified by ESI-MS/MS and NMR. Half-lives ranging
      from hours to days (in the case of the monoethyl ester) show that it is possible
      to design molecules with variable half-lives with potential to be used for
      biological intervention experiments as possible inhibitors of biosignaling
      processes or as haptens for the generation of antibodies.

PMID- 21861471
TI  - Basis for half-site ligand binding in yeast NAD(+)-specific isocitrate
      dehydrogenase.
AB  - Yeast NAD(+)-specific isocitrate dehydrogenase is an allosterically regulated
      octameric enzyme composed of four heterodimers of a catalytic IDH2 subunit and a
      regulatory IDH1 subunit. Despite structural predictions that the enzyme would
      contain eight isocitrate binding sites, four NAD(+) binding sites, and four AMP
      binding sites, only half of the sites for each ligand can be measured in binding
      assays. On the basis of a potential interaction between side chains of Cys-150
      residues in IDH2 subunits in each tetramer of the enzyme, ligand binding assays
      of wild-type (IDH1/IDH2) and IDH1/IDH2(C150S) octameric enzymes were conducted in
      the presence of dithiothreitol. These assays demonstrated the presence of eight
      isocitrate and four AMP binding sites for the wild-type enzyme in the presence of
      dithiothreitol and for the IDH1/IDH2(C150S) enzyme in the absence or presence of
      this reagent, suggesting that interactions between sulfhydryl side chains of IDH2
      Cys-150 residues limit access to these sites. However, only two NAD(+) sites
      could be measured for either enzyme. A tetrameric form of IDH (an IDH1(G15D)/IDH2
      mutant enzyme) demonstrated half-site binding for isocitrate (two sites) in the
      absence of dithiothreitol and full-site binding (four sites) in the presence of
      dithiothreitol. Only one NAD(+) site could be measured for the tetramer under
      both conditions. In the context of the structure of the enzyme, these results
      suggest that an observed asymmetry between heterotetramers in the holoenzyme
      contributes to interactions between IDH2 Cys-150 residues and to half-site
      binding of isocitrate, but that a form of negative cooperativity may limit access
      to apparently equivalent NAD(+) binding sites.

PMID- 21861473
TI  - Adsorption of n-butanol from dilute aqueous solution with grafted calixarenes.
AB  - Materials were synthesized for the recovery of n-butanol from dilute aqueous
      solutions, as may be useful for applications in biofuel-water separations. These
      materials are composed of hydrophobic, cavity-containing calixarenes covalently
      bound directly to porous, hydrophilic silica supports through a Si linker atom
      rather than a flexible organic linker, as is common, at surface coverages of up
      to ~0.25 calixarenes/nm(2) (~250 MUmol calix/g matl). The calixarene ring size,
      upper rim groups, bridging group (calixarene vs thiacalixarene), and surface
      density were varied. The materials were characterized by NMR, UV-vis, and TGA.
      The absolute butanol uptake reached ~0.16 mmol butanol per gram of material at
      equilibrium concentrations below 0.12 M and increased monotonically with the
      calixarene surface density. The background adsorption onto the silica surface was
      small at high calixarene loading. At 298 K, the free energy of adsorption in the
      calixarene cavities became more favorable by 3 kJ/mol as the surface area of the
      hydrophobic calixarene upper rim groups increased from H to methyl to tert-butyl,
      consistent with adsorption driven by van der Waals interactions. A
      thiacalix[4]arene-SiO(2) material, containing polarizable sulfur bridges and a
      larger, more conformationally mobile calixarene structure, had slightly stronger
      adsorption still. All materials except this thiacalixarene exhibited fully
      reversible adsorption into solution. As a representative material, the adsorption
      of n-butanol from aqueous solution at a tert-butylcalix[4]arene site was
      accompanied by a negligible enthalpy change but a small, favorable entropy change
      of +50 +/- 20 J/mol/K, indicating that adsorption is driven by desolvation.
      Butanol desorbed from tert-butylcalix[4]arene materials at ~150  degrees C into
      the gas phase, well within the range of stability of calixarenes (<300  degrees
      C), indicating that these materials have promise as regenerable adsorbents.

PMID- 21861474
TI  - A reel-wound carbon nanotube polarizer for terahertz frequencies.
AB  - Utilizing highly oriented multiwalled carbon nanotube aerogel sheets, we
      fabricated micrometer-thick freestanding carbon nanotube (CNT) polarizers. Simple
      winding of nanotube sheets on a U-shaped polyethylene reel enabled rapid and
      reliable polarizer fabrication, bypassing lithography or chemical etching
      processes. With the remarkable extinction ratio reaching ~37 dB in the broad
      spectral range from 0.1 to 2.0 THz, combined with the extraordinary gravimetric
      mechanical strength of CNTs, and the dispersionless character of freestanding
      sheets, the commercialization prospects for our CNT terahertz polarizers appear
      attractive.

PMID- 21861475
TI  - Dissolution of microscale energetic residues in saturated porous media:
      visualization and quantification at the pore-scale by spectral confocal
      microscopy.
AB  - Microscale energetic residues (<1 mm) are produced during munitions detonation
      and the weathering of larger residues, and may serve as mobile and fast
      dissolving sources of explosive compounds, such as 2,4,6-trinitrotoluene (TNT),
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetrazocine (HMX). Knowledge of the behavior of microscale energetic
      residues in subsurface environments is quite limited. This work employed a
      previously unreported property of TNT, RDX, and HMX (i.e., autofluorescence under
      405 nm laser illumination) to visualize and quantify the dissolution of
      microscale physically attrited energetic residues in saturated porous media. The
      results demonstrated that within the Composition B particles, TNT dissolved
      preferentially over RDX/HMX and the mass ratio of RDX/HMX to TNT increased by
      >5.3 times initially. The focused particles dissolved in a stepwise fashion, with
      >72% of particle volume reduction in <36 min. Moreover, the results suggested
      that the particle shape factor was relatively stable and the particles retained
      their highly irregular shape throughout the dissolution processes. This is the
      first work to demonstrate application of spectral confocal microscopy for
      visualizing and quantifying the behavior of energetic residues at the pore-scale.

PMID- 21861476
TI  - Enhanced adsorption of PFOA and PFOS on multiwalled carbon nanotubes under
      electrochemical assistance.
AB  - Removal of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)
      from aqueous solution has attracted wide attention in light of their
      environmental persistence, bioaccumulation, and potential toxicity. Although
      various destructive technologies were developed, removal of PFOX (X = A and S)
      under mild conditions are still desirable. In this work, multiwalled carbon
      nanotubes (MWNTs) were applied to remove PFOX in electrochemically assistant
      adsorption. Electrosorption kinetics and isotherms were investigated relative to
      open circuit (OC) adsorption and adsorption on powder MWNTs. Compared with powder
      MWNTs adsorption, the initial adsorption rate (upsilon(0)) of 100 MUg/L PFOX at
      0.6 V increased 60-fold (PFOA) and 41-fold (PFOS) according to pseudosecond-order
      kinetics model and the maximum electrosorption capacity (q(m)) of PFOX (50 MUg/L
      to 10 mg/L) increased 150-fold (PFOA) and 94-fold (PFOS) simulated with Langmuir
      model. These significant improvements were assumed to benefit from enhanced
      electrostatic attraction under electrochemical assistance. Furthermore, the used
      MWNTs were found to be regenerative and reusable. This work provides not only a
      new approach to effective removal of perfluorochemicals from aqueous solution but
      also a low energy-consumption and environmentally-friendly strategy for
      application of carbon nanotubes in water treatment.

PMID- 21861478
TI  - Cyclizations of alkynes: revisiting Baldwin's rules for ring closure.

PMID- 21861477
TI  - 2,4,5-Trichlorophenol degradation using a novel TiO2-coated biofilm carrier:
      roles of adsorption, photocatalysis, and biodegradation.
AB  - Intimate coupling of photocatalysis and biodegradation (ICPB) offers potential
      for degrading biorecalcitrant and toxic organic compounds. This study reports on
      a novel sponge-type, TiO(2)-coated biofilm carrier that showed significant
      adherence of TiO(2) and ability to accumulate biomass in its interior. This
      carrier was tested for ICPB in a continuous-flow photocatalytic circulating-bed
      biofilm reactor (PCBBR) to mineralize 2,4,5-trichlorophenol (TCP), which is
      biorecalcitrant. Four mechanisms possibly acting in ICPB were tested separately:
      TCP adsorption to the carrier, UV photolysis, UV photocatalysis, and
      biodegradation by biofilm inside the carrier. The carrier exhibited strong TCP
      adsorption that followed a Freundlich isotherm with an exponent near 2. Whereas
      UV photolysis was negligible, photocatalysis produced TCP-degradation products
      that could be mineralized, and the strong adsorption of TCP to the carrier
      enhanced biodegradation by relieving toxicity. Validating the ICPB concept,
      biofilm was protected inside the carriers, although biomass originally on the
      outer surface of the carriers was eliminated. ICPB significantly lowered the
      diversity of the bacterial community, but five genera known to biodegrade
      chlorinated phenols (Ralstonia, Bradyrhizobium, Methylobacterium, Cupriavidus,
      and Pandoraea) were markedly enriched.

PMID- 21861479
TI  - Pd-catalyzed C4-olefination of oxazoles via C-H bond activation: divergent
      synthesis of functionalized amino alcohol and amino acid derivatives.
AB  - A Pd-catalyzed C4-olefination of oxazoles via C-H bond activation under mild
      conditions was achieved. The reaction was shown to be general over a range of
      substrates. New protocols for the divergent transformation of these products to
      provide functionalized amino alcohol and amino acid derivatives have also been
      established.

PMID- 21861480
TI  - Varietal relationship between instrumental skin hardness and climate for
      grapevines (Vitis vinifera L.).
AB  - The main aims of this work were to classify 30 colored and white wine grape
      varieties according to the berry skin hardness, to assess the influence of annual
      variations in climate on the berry skin hardness, and to establish significant
      relationships among berry skin mechanical properties and some climatic
      bioclimatic indices calculated for different grape-ripening periods, close to the
      harvest date. The results obtained show that the most influential bioclimatic
      indices on the skin mechanical attributes were temperature parameters. In the
      same season, the influence of the production area was also evaluated,
      precipitation parameters being the best correlated with the berry skin hardness.
      This first work has permitted us to know the relationship among skin texture
      characteristics and seasonal climatic indices.

PMID- 21861481
TI  - Gram-scale synthesis of silica nanotubes with controlled aspect ratios by
      templating of nickel-hydrazine complex nanorods.
AB  - We have developed a robust method for the synthesis of silica nanotubes with
      controlled aspect ratios on a large scale by templating against rod-like
      nanocrystals. Crystalline nanorods of a nickel-hydrazine complex are first formed
      in reverse micelles by surfactant capping on side facets, and subsequent silica
      coating and selective etching give rise to silica nanotubes of high uniformity
      and yield. The length of the silica nanotubes is tunable in the range 37-340 nm
      and can reach as long as micrometers. Control of the length is conveniently
      achieved by tuning the hydrazine/nickel ratio, which affects the growth kinetics
      of the nanocrystal templates. The inner diameter of the silica nanotubes can be
      adjusted in the range 10-20 nm by choosing different surfactants. This method is
      unique in utilizing reverse micelles as discrete nanoscale reactors for the
      growth of nanocrystals, allowing for precise control of the features of the
      nanotubes and opening up new opportunities in the synthesis of novel anisotropic
      nanomaterials, construction of nanodevices, and potential drug delivery
      applications.

PMID- 21861482
TI  - Ultrafast vibrations of gold nanorings.
AB  - We investigate the vibrational modes of gold nanorings on a silica substrate with
      an ultrafast optical technique. By comparison with numerical simulations, we
      identify several resonances in the gigahertz range associated with axially
      symmetric deformations of the nanoring and substrate. We elucidate the
      corresponding mode shapes and find that the substrate plays an important role in
      determining the mode damping. This study demonstrates the need for a plasmonic
      nano-optics approach to understand the optical excitation and detection
      mechanisms for the vibrations of plasmonic nanostructures.

PMID- 21861483
TI  - In silico partitioning and transmembrane insertion of hydrophobic peptides under
      equilibrium conditions.
AB  - Nascent transmembrane (TM) polypeptide segments are recognized and inserted into
      the lipid bilayer by the cellular translocon machinery. The recognition rules,
      described by a biological hydrophobicity scale, correlate strongly with physical
      hydrophobicity scales that describe the free energy of insertion of TM helices
      from water. However, the exact relationship between the physical and biological
      scales is unknown, because solubility problems limit our ability to measure
      experimentally the direct partitioning of hydrophobic peptides across lipid
      membranes. Here we use microsecond molecular dynamics (MD) simulations in which
      monomeric polyleucine segments of different lengths are allowed to partition
      spontaneously into and out of lipid bilayers. This approach directly reveals all
      states populated at equilibrium. For the hydrophobic peptides studied here, only
      surface-bound and transmembrane-inserted helices are found. The free energy of
      insertion is directly obtained from the relative occupancy of these states. A
      water-soluble state was not observed, consistent with the general insolubility of
      hydrophobic peptides. The approach further allows determination of the
      partitioning pathways and kinetics. Surprisingly, the transfer free energy
      appears to be independent of temperature, which implies that surface-to-bilayer
      peptide insertion is a zero-entropy process. We find that the partitioning free
      energy of the polyleucine segments correlates strongly with values from
      translocon experiments but reveals a systematic shift favoring shorter peptides,
      suggesting that translocon-to-bilayer partitioning is not equivalent but related
      to spontaneous surface-to-bilayer partitioning.

PMID- 21861484
TI  - Evaluating the efficacy of amino acids as CO2 capturing agents: a first
      principles investigation.
AB  - Comprehension of the basic concepts for the design of systems for CO2 adsorption
      is imperative for increasing interest in technology for CO2 capture from the
      effluents. The efficacy of 20 naturally occurring amino acids (AAs) is
      demonstrated as the most potent CO2 capturing agents in the process of chemical
      absorption and physisorption through a systematic computational study using
      highly parametrized M05-2X/6-311+G(d,p) method. The ability of AAs to bind CO2
      both in the noncovalent and covalent fashion and presence of multiple adsorption
      sites with varying magnitude of binding strengths in all 20 AAs makes them as
      most promising materials in the process of physisorption. The binding energies
      (BEs) estimating the strength of noncovalent interaction of AAs and CO2 are
      calculated and results are interpreted in terms of the nature and strength of the
      various types of cooperative interactions which are present. The study underlines
      the possibility to engineer the porous solid materials with extended networks by
      judiciously employing AA chains as linkers which can substantially augment their
      efficacy. Results show that a significant increase in the CO2...AA affinity is
      achieved in the case of AAs with polar neutral side chains. Furthermore, the
      study proposes AAs as effective alternatives to alkanolamines in chemical
      dissolution of CO2.

PMID- 21861485
TI  - Magnetic proximity effect as a pathway to spintronic applications of topological
      insulators.
AB  - Spin-based electronics in topological insulators (TIs) is favored by the long
      spin coherence(1,2) and consequently fault-tolerant information storage.
      Magnetically doped TIs are ferromagnetic up to 13 K,(3) well below any practical
      operating condition. Here we demonstrate that the long-range ferromagnetism at
      ambient temperature can be induced in Bi(2-x)Mn(x)Te(3) by the magnetic proximity
      effect through deposited Fe overlayer. This result opens a new path to interface
      controlled ferromagnetism in TI-based spintronic devices.

PMID- 21861486
TI  - Bridge-mediated excitation energy transfer pathways through protein media: a
      Slater determinant-based electronic coupling calculation combined with localized
      molecular orbitals.
AB  - A computational method for calculating electronic coupling and pathway of
      electron transfer (ET) has been extended to that for excitation energy transfer
      (EET). A molecular orbital (MO)-based description has been generalized to one
      based on Slater determinants. This approach reduces the approximations used for
      the Green's function method from the perturbation of chemical-bond interactions
      to the perturbation of the configuration interactions. It is, therefore,
      reasonable to apply this method to EET, which involves the transfer of an
      electron-hole pair. To represent EET donor, acceptor, and bridge states, we
      adopted recently developed localized molecular orbitals (LMOs) for constructing
      locally excited determinants. The LMO approach provides a chemically meaningful
      interpretation of how each local excitation on the bridge contributes to the
      total electronic coupling of the EET. We applied the method to six model peptides
      and calculated their electronic couplings as well as the direct and through
      peptide terms. Although the through-peptide term is usually negligibly small
      compared with the direct term, it can dominate the EET reaction in appropriate
      situations. The direct term dominates in long-range interactions because the
      indirect term decays in shorter distances.

PMID- 21861487
TI  - Targeting the heat shock protein 90 dimer with dimeric inhibitors.
AB  - The design, synthesis, and biological evaluation of conformationally constrained
      coumermycin A1 analogues are reported. Compounds were evaluated against both
      breast cancer (SKBr3 and MCF7) and prostate cancer (PC3 mm2, A549, and HT29) cell
      lines. Non-noviosylated coumermycin A1 analogues that manifest potent
      antiproliferative activity resulting from Hsp90 inhibition are provided, wherein
      replacement of the stereochemically complex noviose sugar with readily available
      piperidine rings resulted in ~100 fold increase in antiproliferative activities
      as compared to coumermycin A1, producing small molecule Hsp90 inhibitors that
      exhibit nanomolar activities.

PMID- 21861489
TI  - Single-electrolyte isotachophoresis using a nanochannel-induced depletion zone.
AB  - Isotachophoretic separations are triggered at the border of a nanochannel-induced
      ion-depleted zone. This depletion zone acts as a terminating electrolyte and is
      created by concentration polarization over the nanochannel. We show both
      continuous and discrete sample injections as well as separation of up to four
      analytes. Continuous injection of a spacer compound was used for selective
      analyte elution. Zones were kept focused for over one hour, while shifting less
      than 700 MUm. Moreover, zones could be deliberately positioned in the separation
      channel and focusing strength could be precisely tuned employing a three-point
      voltage actuation scheme. This makes depletion zone isotachophoresis (dzITP) a
      fully controllable single-electrolyte focusing and separation technique. For on
      chip electrokinetic methods, dzITP sets a new standard in terms of versatility
      and operational simplicity.

PMID- 21861488
TI  - Highly practical copper(I)/TEMPO catalyst system for chemoselective aerobic
      oxidation of primary alcohols.
AB  - Aerobic oxidation reactions have been the focus of considerable attention, but
      their use in mainstream organic chemistry has been constrained by limitations in
      their synthetic scope and by practical factors, such as the use of pure O(2) as
      the oxidant or complex catalyst synthesis. Here, we report a new (bpy)Cu(I)/TEMPO
      catalyst system that enables efficient and selective aerobic oxidation of a broad
      range of primary alcohols, including allylic, benzylic, and aliphatic
      derivatives, to the corresponding aldehydes using readily available reagents, at
      room temperature with ambient air as the oxidant. The catalyst system is
      compatible with a wide range of functional groups and the high selectivity for 1
      degrees  alcohols enables selective oxidation of diols that lack protecting
      groups.

PMID- 21861490
TI  - Stereoselective multimodal transformations of planar chiral 9-membered diallylic
      amides.
AB  - Intermolecular reactions of planar chiral 9-membered diallylic amides provide a
      variety of bicyclic compounds with central chiralities in a stereospecific
      fashion with high group selectivity. Lewis-acid-promoted intramolecular reactions
      of the obtained bicyclic compounds provide transannular products in a
      stereospecific fashion. Furthermore, a direct transannular reaction of diallylic
      amide involving sequential intermolecular-intramolecular reactions has been
      developed.

PMID- 21861491
TI  - The evolution of the protein corona around nanoparticles: a test study.
AB  - The importance of the protein corona formed around nanoparticles upon entering a
      biological fluid has recently been highlighted. This corona is, when sufficiently
      long-lived, thought to govern the particles' biological fate. However, even this
      long-lived "hard" corona evolves and re-equilibrates as particles pass from one
      biological fluid to another, and may be an important feature for long-term fate.
      Here we show the evolution of the protein corona as a result of transfer of
      nanoparticles from one biological fluid (plasma) into another (cytosolic fluid),
      a simple illustrative model for the uptake of nanoparticles into cells. While no
      direct comparison can be made to what would happen in, for example, the uptake
      pathway, the results confirm that significant evolution of the corona occurs in
      the second biological solution, but that the final corona contains a
      "fingerprint" of its history. This could be evolved to map the transport pathways
      utilized by nanoparticles, and eventually to predict nanoparticle fate and
      behavior.

PMID- 21861492
TI  - New A-A-D-A-A-type electron donors for small molecule organic solar cells.
AB  - Two A-A-D-A-A-type molecules (BCNDTS and BDCDTS), where two terminal electron
      withdrawing cyano or dicyanovinylene moieties are connected to a central
      dithienosilole core through another electron-accepting 2,1,3-benzothiadiazole
      block, have been synthesized, characterized, and employed as electron donors for
      small molecule organic solar cells. Vacuum-deposited bilayer and planar mixed
      heterojunction devices based on BCNDTS and fullerene acceptors (C(60) or C(70))
      exhibited decent power conversion efficiencies of 2.3% and 3.7%, respectively.

PMID- 21861493
TI  - Catalytic and biochemical features of a monoclonal antibody heavy chain, JN1-2,
      raised against a synthetic peptide with a hemagglutinin molecule of influenza
      virus.
AB  - It has long been an important issue to produce a catalytic antibody that
      possesses the ability to lose the infectivity of a bacteria or virus. The
      monoclonal antibody JN1-2 was generated using a synthetic peptide
      (TGLRNGITNKVNSVIEKAA) conjugated with human IgG. The peptide sequence includes
      the conserved region of the hemagglutinin molecule (HA(1) and HA(2) domains),
      which locates on the envelope of the influenza virus and plays an important role
      in influenza A virus infection. The monoclonal antibody specifically reacted with
      the HA2 domain, not only of H2 but also of an H1 strain of the H1N1 subtype (H1
      strain). The heavy chain (JN1-2-H) isolated from the parent antibody showed
      catalytic activity cleaving the above antigenic peptide with very high turnover
      (kcat = 26 min(-1)), and it could slowly degrade the recombinant HA(2) domain by
      the catalytic function. Interestingly, the heavy chain exhibited the ability to
      reduce the infectivity of type A H1N1 but not type B, indicating specificity to
      type A. This characteristic monoclonal catalytic antibody heavy chain could
      suppress the infection of the influenza virus in vitro assays.

PMID- 21861494
TI  - Tritoniopsins A-D, cladiellane-based diterpenes from the South China Sea
      nudibranch Tritoniopsis elegans and its prey Cladiella krempfi.
AB  - Four diterpenes, tritoniopsins A-D (1-4), have been isolated from the South China
      Sea nudibranch Tritoniopsis elegans and its prey, the soft coral Cladiella
      krempfi. They display an unprecedented pyran ring in the cladiellane framework,
      thus representing a novel cladiellane-based diterpene family. Their structures
      have been mainly characterized by NMR and mass spectrometric techniques, whereas
      the relative configuration of compound 1 was secured by X-ray analysis.
      Antiproliferative assays on tumor and nontumor cell lines have been carried out
      for the main metabolite, tritoniopsin B (2).

PMID- 21861495
TI  - Three banana-shaped arsenomolybdates encapsulating a hexanuclear transition-metal
      central magnetic cluster: [As(III)2Fe(III)5MMo22O85(H2O)]n- (M = Fe3+, n = 14; M
      = Ni2+ and Mn2+, n = 15).
AB  - Three polyoxometalates encapsulating high-nuclearity magnetic clusters MFe(5),
      [As(2)MFe(5)Mo(22)O(85)(H(2)O)](n-) (M = Fe(3+), n = 14; M = Ni(2+) and Mn(2+), n
      = 15), were synthesized and characterized by single-crystal X-ray diffraction,
      elemental analysis, infrared spectroscopy, thermogravimetric analysis, and
      magnetism measurements. The polyanion [As(2)MFe(5)Mo(22)O(85)(H(2)O)](n-)
      consists of a central MMo(7)O(28) (M = Fe(3+), Ni(2+), and Mn(2+)) fragment and
      two AsMo(7)O(27) fragments linked together by two trimeric clusters,
      Fe(2)MoO(MU(2)-O)(2) and Fe(3)(H(2)O), to form a banana-shaped structure with
      C(1) symmetry. The MMo(7)O(28) and AsMo(7)O(27) units have a similar structure
      and can be considered as a monocapped hexavacant alpha-B-Keggin subunit with a
      central MO(4) group or a central As(III)O(3) group. The polyoxometalates have a
      low absorption of upsilon(Mo-O(d)) (925-913 cm(-1)) because most of the Mo atoms
      in the polyanions have at least two longer Mo-O(d) bonds. The framework of the
      arsenomolybdates is stable before As(2)O(3) escaping (ca. 300  degrees C). The
      analysis of magnetostructural correlations and magnetism measurements indicate
      the coexistence of ferro- and antiferromagnetic interactions, which give an
      overall ferromagnetic spin ground state in the compounds.

PMID- 21861497
TI  - Toward bioinspired galectin mimetics: identification of ligand-contacting
      peptides by proteolytic-excision mass spectrometry.
AB  - Clinically relevant bioactivities of human galectins (adhesion/growth-regulatory
      galactoside-specific lectins) inspired the design of peptides as new tools to
      elicit favorable effects (e.g., in growth control) or block harmful binding
      (e.g., in tissue invasion). To obtain the bioinspired lead compounds, we combined
      a proteolytic fragmentation approach without/with ligand contact (excision) with
      mass spectrometric identification of affinity-bound protein fragments, using
      galectin-1 and -3 as models. Two peptides from the carbohydrate recognition
      domains were obtained in each case in experimental series rigorously controlled
      for specificity, and the [157-162] peptide of galectin-3 proved to be active in
      blocking lectin binding to a neoglycoprotein and to tumor cell surfaces. This
      approach affords peptide sequences for structural optimization and
      intrafamily/phylogenetic galectin comparison at the binding-site level with a
      minimal requirement of protein quantity, and it is even amenable to mixtures.

PMID- 21861498
TI  - Rolled-up magnetic sensor: nanomembrane architecture for in-flow detection of
      magnetic objects.
AB  - Detection and analysis of magnetic nanoobjects is a crucial task in modern
      diagnostic and therapeutic techniques applied to medicine and biology.
      Accomplishment of this task calls for the development and implementation of
      electronic elements directly in fluidic channels, which still remains an open and
      nontrivial issue. Here, we present a novel concept based on rolled-up
      nanotechnology for fabrication of multifunctional devices, which can be
      straightforwardly integrated into existing fluidic architectures. We apply strain
      engineering to roll-up a functional nanomembrane consisting of a magnetic sensor
      element based on [Py/Cu](30) multilayers, revealing giant magnetoresistance
      (GMR). The comparison of the sensor's characteristics before and after the roll
      up process is found to be similar, allowing for a reliable and predictable method
      to fabricate high-quality ultracompact GMR devices. The performance of the rolled
      up magnetic sensor was optimized to achieve high sensitivity to weak magnetic
      fields. We demonstrate that the rolled-up tube itself can be efficiently used as
      a fluidic channel, while the integrated magnetic sensor provides an important
      functionality to detect and respond to a magnetic field. The performance of the
      rolled-up magnetic sensor for the in-flow detection of ferromagnetic CrO(2)
      nanoparticles embedded in a biocompatible polymeric hydrogel shell is
      highlighted.

PMID- 21861499
TI  - Characterization of photoinduced self-exchange reactions at molecule
      semiconductor interfaces by transient polarization spectroscopy: lateral
      intermolecular energy and hole transfer across sensitized TiO2 thin films.
AB  - Transient anisotropy measurements are reported as a new spectroscopic tool for
      mechanistic characterization of photoinduced charge-transfer and energy-transfer
      self-exchange reactions at molecule-semiconductor interfaces. An anisotropic
      molecular subpopulation was generated by photoselection of randomly oriented
      Ru(II)-polypyridyl compounds, anchored to mesoscopic nanocrystalline TiO(2) or
      ZrO(2) thin films, with linearly polarized light. Subsequent characterization of
      the photoinduced dichromism change by visible absorption and photoluminescence
      spectroscopies on the nano- to millisecond time scale enabled the direct
      comparison of competitive processes: excited-state decay vs self-exchange energy
      transfer, or interfacial charge recombination vs self-exchange hole transfer.
      Self-exchange energy transfer was found to be many orders-of-magnitude faster
      than hole transfer at the sensitized TiO(2) interfaces; for
      [Ru(dtb)(2)(dcb)](PF(6))(2), where dtb is 4,4'-(C(CH(3))(3))(2)-2,2'-bipyridine
      and dcb is 4,4'-(COOH)(2)-2,2'-bipyridine, anchored to TiO(2), the energy
      transfer correlation time was theta(ent) = 3.3 MUs while the average hole
      transfer correlation time was <theta(h+)> = 110 ms, under identical experimental
      conditions. Monte Carlo simulations successfully modeled the anisotropy decays
      associated with lateral energy transfer. These mesoscopic, nanocrystalline TiO(2)
      thin films developed for regenerative solar cells thus function as active
      "antennae", harvesting sunlight and transferring energy across their surface. For
      the dicationic sensitizer, [Ru(dtb)(2)(dcb)](PF(6))(2), anisotropy changes
      indicative of self-exchange hole transfer were observed only when ions were
      present in the acetonitrile solution. In contrast, evidence for lateral hole
      transfer was observed in neat acetonitrile for a neutral sensitizer, cis
      Ru(dnb)(dcb)(NCS)(2), where dnb is 4,4'-(CH(3)(CH(2))(8))(2)-2,2'-bipyridine,
      anchored to TiO(2). The results indicate that mechanistic models of interfacial
      charge recombination between electrons in TiO(2) and oxidized sensitizers must
      take into account diffusion of the injected electron and the oxidized sensitizer.
      The phenomena presented herein represent two means of concentrating potential
      energy derived from visible light that could be used to funnel energy to
      molecular catalysts for multiple-charge-transfer reactions, such as the
      generation of solar fuels.

PMID- 21861500
TI  - Dynamic double lattice of 1-adamantaneselenolate self-assembled monolayers on
      Au{111}.
AB  - We report a complex, dynamic double lattice for 1-adamantaneselenolate monolayers
      on Au{111}. Two lattices coexist, revealing two different binding modes for
      selenols on gold: molecules at bridge sites have lower conductance than molecules
      at three-fold hollow sites. The monolayer is dynamic, with molecules switching
      reversibly between the two site-dependent conductance states. Monolayer dynamics
      enable adsorbed molecules to reorganize according to the underlying gold
      electronic structure over long distances, which facilitates emergence of the self
      organized rows of dimers. The low-conductance molecules assume a (7 * 7) all
      bridge configuration, similar to the analogous 1-adamantanethiolate monolayers on
      Au{111}. The high-conductance molecules self-organize upon mild annealing into
      distinctive rows of dimers with long-range order, described by a (6?5 * 6?5)R15
      degrees  unit cell.

PMID- 21861501
TI  - Silver nanoparticle synthesis: novel route for laser triggering of
      polyelectrolyte capsules.
AB  - We have demonstrated the synthesis of light-sensitive polyelectrolyte capsules
      (PECs) by utilizing a novel polyol reduction method and investigated its
      applicability as photosensitive drug delivery vehicle. The nanostructured
      capsules were prepared via layer by layer (LbL) assembly of poly(allylamine
      hydrochloride) (PAH) and dextran sulfate (DS) on silica particles followed by in
      situ synthesis of silver nanoparticles (NPs). Capsules without silver NPs were
      permeable to low molecular weight (M(w), 479 g/mol) rhodamine but impermeable to
      higher molecular weight fluorescence labeled dextran (FITC-dextran). However,
      capsules synthesized with silver NPs showed porous morphology and were permeable
      to higher molecular weight (M(w) 70 kDa) FITC-dextran also. These capsules were
      loaded with FITC-dextran using thermal encapsulation method by exploiting
      temperature induced shrinking of the capsules. During heat treatment the porous
      morphology of the capsules transformed into smooth pore free structure which
      prevents the movement of dextran into bulk during the loading process. When these
      loaded capsules are exposed to laser pulses, the capsule wall ruptured, resulting
      in the release of the loaded drug/dye. The rupture of the capsules was dependent
      on particle size, laser pulse energy and exposure time. The release was linear
      with time when pulse energy of 400 MUJ was used and burst release was observed
      when pulse energy increased to 600 MUJ.

PMID- 21861502
TI  - The HSP terminator of Arabidopsis thaliana induces a high level of miraculin
      accumulation in transgenic tomatoes.
AB  - High-level accumulation of the target recombinant protein is a significant issue
      in heterologous protein expression using transgenic plants. Miraculin, a taste
      modifying protein, was accumulated in transgenic tomatoes using an expression
      cassette in which the miraculin gene was expressed by the cauliflower mosaic
      virus (CaMV) 35S promoter and the heat shock protein (HSP) terminator (MIR-HSP).
      The HSP terminator was derived from heat shock protein 18.2 in Arabidopsis
      thaliana . Using this HSP-containing cassette, the miraculin concentration in T0
      transgenic tomato lines was 1.4-13.9% of the total soluble protein (TSP), and
      that in the T1 transgenic tomato line homozygous for the miraculin gene reached
      17.1% of the TSP. The accumulation level of the target protein was comparable to
      levels observed with chloroplast transformation. The high-level accumulation of
      miraculin in T0 transgenic tomato lines achieved by the HSP terminator was
      maintained in the successive T1 generation, demonstrating the genetic stability
      of this accumulation system.

PMID- 21861503
TI  - Atomic solid state energy scale.
AB  - A plot of electron affinity (EA) and ionization potential (IP) versus energy band
      gap (E(G)) for 69 binary closed-shell inorganic semiconductors and insulators
      reveals that E(G) is centered about the hydrogen donor/acceptor ionization energy
      epsilon(+/-). Thus, epsilon(+/-), or equivalently the standard hydrogen electrode
      (SHE) energy, functions as an absolute energy reference, determining the tendency
      of an atom to be either a cation or anion in a compound. This empirical trend
      establishes the basis for defining a new solid state energy (SSE) scale. This SSE
      scale makes possible simple approaches for quantitatively assessing
      electronegativity, chemical hardness, and ionicity, while also providing new
      insight into the periodic trends of solids.

PMID- 21861504
TI  - Synthesis of nickel nanowires via electroless nanowire deposition on
      micropatterned substrates.
AB  - Electroless nanowire deposition on micropatterned substrates (ENDOM) is a
      promising new technique by which to direct the synthesis and precise placement of
      metallic nanowires. ENDOM is generally applicable to the preparation of metallic,
      semiconducting, and even insulating nanowires on technologically relevant
      substrates, is inexpensive, and can achieve high growth rates. The deposited
      nanowires are ultralong (centimeters) and can be patterned in arbitrary shapes.
      We demonstrate ENDOM using the growth of nickel nanowires. By controlling the
      deposition time, the width of the nanowires can be varied from 200 to 1000 nm and
      the height can be varied from 7 to 20 nm.

PMID- 21861505
TI  - Ferroelectric behavior in bismuth ferrite thin films of different thickness.
AB  - The ferroelectric behavior of BiFeO(3) thin films is modified by changing the
      film thicknesses, where the BiFeO(3) thin films with different thicknesses were
      grown on SrRuO(3)/Pt/TiO(2)/SiO(2)/Si(100) substrates by radio frequency
      sputtering. The mixture of (110) and (111) orientations is induced for all
      BiFeO(3) thin films regardless of their thicknesses, together with the columnar
      structure and the dense microstructure. Their dielectric behavior is almost
      independent of the film thickness where all thin films have a low dielectric
      loss. A giant remanent polarization of 2P(r) ~ 156.6-188.8 MUC/cm(2) is induced
      for the BiFeO(3) thin films in the thickness range of 190-600 nm. As a result, it
      is an effective way to improve the ferroelectric behavior of the BiFeO(3) thin
      film by tailoring the film thickness.

PMID- 21861506
TI  - Short-term memory to long-term memory transition in a nanoscale memristor.
AB  - "Memory" is an essential building block in learning and decision-making in
      biological systems. Unlike modern semiconductor memory devices, needless to say,
      human memory is by no means eternal. Yet, forgetfulness is not always a
      disadvantage since it releases memory storage for more important or more
      frequently accessed pieces of information and is thought to be necessary for
      individuals to adapt to new environments. Eventually, only memories that are of
      significance are transformed from short-term memory into long-term memory through
      repeated stimulation. In this study, we show experimentally that the retention
      loss in a nanoscale memristor device bears striking resemblance to memory loss in
      biological systems. By stimulating the memristor with repeated voltage pulses, we
      observe an effect analogous to memory transition in biological systems with much
      improved retention time accompanied by additional structural changes in the
      memristor. We verify that not only the shape or the total number of stimuli is
      influential, but also the time interval between stimulation pulses (i.e., the
      stimulation rate) plays a crucial role in determining the effectiveness of the
      transition. The memory enhancement and transition of the memristor device was
      explained from the microscopic picture of impurity redistribution and can be
      qualitatively described by the same equations governing biological memories.

PMID- 21861507
TI  - Electronic absorption spectra of protonated pyrene and coronene in neon matrixes.
AB  - Protonated pyrene and coronene have been isolated in 6 K neon matrixes. The
      cations were produced in the reaction of the parent aromatics with protonated
      ethanol in a hot-cathode discharge source, mass selected, and co-deposited with
      neon. Three electronic transitions of the most stable isomer of protonated pyrene
      and four of protonated coronene were recorded. The strongest, S(1) <- S(0)
      transitions, are in the visible region, with onset at 487.5 nm for protonated
      pyrene and 695.6 nm for protonated coronene. The corresponding neutrals were also
      observed. The absorptions were assigned on the basis of ab initio coupled-cluster
      and time-dependent density functional theory calculations. The astrophysical
      relevance of protonated polycyclic aromatic hydrocarbons is discussed.

PMID- 21861508
TI  - The role of cobalt phosphate in enhancing the photocatalytic activity of alpha
      Fe2O3 toward water oxidation.
AB  - Transient absorption spectroscopy was used to probe the dynamics of
      photogenerated charge carriers in alpha-Fe(2)O(3)/CoO(x) nanocomposite
      photoelectrodes for water splitting. The addition of cobalt-based
      electrocatalysts was observed to increase the lifetime of photogenerated holes in
      the photoelectrode by more than 3 orders of magnitude without the application of
      electrical bias. We therefore propose that the enhanced photoelectrochemical
      activity of the composite electrode for water photooxidation results, at least in
      part, from reduced recombination losses because of the formation of a Schottky
      type heterojunction.

PMID- 21861509
TI  - Numerical construction of the p(fold) (committor) reaction coordinate for a
      Markov process.
AB  - To simplify the description of a complex multidimensional dynamical process, one
      often projects it onto a single reaction coordinate. In protein folding studies,
      the folding probability p(fold) is an optimal reaction coordinate which preserves
      many important properties of the dynamics. The construction of the coordinate is
      difficult. Here, an efficient numerical approach to construct the p(fold)
      reaction coordinate for a Markov process (satisfying the detailed balance) is
      described. The coordinate is obtained by optimizing parameters of a chosen
      functional form to make a generalized cut-based free energy profile the highest.
      The approach is illustrated by constructing the p(fold) reaction coordinate for
      the equilibrium folding simulation of FIP35 protein reported by Shaw et al.
      (Science 2010, 330, 341-346).

PMID- 21861510
TI  - Sonochemical synthesis of ordered SnO2/CMK-3 nanocomposites and their lithium
      storage properties.
AB  - In this study, we successfully prepare SnO(2) nanoparticles inside the pore
      channels of CMK-3 ordered mesoporous carbon via sonochemical method. The content
      of SnO(2) is 17 wt % calculated according to the energy-dispersive X-ray
      spectroscopy (EDS) result. CMK-3 with 17 wt % loading of SnO(2) nanoparticles has
      a large specific surface area and pore volume. Electrochemical performance
      demonstrates that the ordered SnO(2)/CMK-3 nanocomposites electrode possesses
      higher reversible capacity and cycling stability than that of original CMK-3
      electrode. Moreover, the ordered SnO(2)/CMK-3 nanocomposites electrode also
      exhibits high capacity at higher charge/discharge rate. The improved
      electrochemical performance is attributed to the nanometer-sized SnO(2) formed
      inside CMK-3 and the large surface area of the mesopores (3.4 nm) in which the
      SnO(2) nanoparticles are formed.

PMID- 21861511
TI  - Excitonic effects on optical absorption spectra of doped graphene.
AB  - We have performed first-principles calculations to study optical absorption
      spectra of doped graphene with many-electron effects included. Both self-energy
      corrections and electron-hole interactions are reduced due to the enhanced
      screening in doped graphene. However, self-energy corrections and excitonic
      effects nearly cancel each other, making the prominent optical absorption peak
      fixed around 4.5 eV under different doping conditions. On the other hand, an
      unexpected increase of the optical absorbance is observed within the infrared and
      visible-light frequency regime (1-3 eV). Our analysis shows that a combining
      effect from the band filling and electron-hole interactions results in such an
      enhanced excitonic effect on the optical absorption. These unique variations of
      the optical absorption of doped graphene are of importance to understand relevant
      experiments and design optoelectronic applications.

PMID- 21861512
TI  - The effects of electron-hole pair coupling on the infrared laser-controlled
      vibrational excitation of NO on Au(111).
AB  - In this work, we present theoretical simulations of laser-driven vibrational
      control of NO adsorbed on a gold surface. Our goal is to tailor laser pulses to
      selectively excite specific modes and vibrational eigenstates, as well as to
      favor photodesorption of the adsorbed molecule. To this end, various control
      schemes and algorithms are applied. For adsorbates at metallic surfaces, the
      creation of electron-hole pairs in the substrate is known to play a dominant role
      in the transfer of energy from the system to the surroundings. These nonadiabatic
      couplings are included perturbatively in our reduced density matrix simulations
      using a generalization of the state-resolved position-dependent anharmonic rate
      model we recently introduced. An extension of the reduced density matrix is also
      proposed to provide a sound model for photodesorption in dissipative systems.

PMID- 21861513
TI  - Dissolution kinetics of polycrystalline calcium sulfate-based materials:
      influence of chemical modification.
AB  - Using a channel flow cell (CFC) system, the dissolution kinetics of
      polycrystalline gypsum-based materials have been examined with the aim of
      understanding their interaction with water, a property that limits the
      applications of the material in many situations. ICP (inductively coupled plasma)
      analysis of elemental concentrations in solution as a function of time yields
      surface fluxes by using a finite element modeling approach to simulate the
      hydrodynamic behavior within the CFC. After correction for surface roughness, a
      value for the intrinsic dissolution flux into water of pure polycrystalline
      gypsum, CaSO(4).2H(2)O, of 1.1 (+/-0.4) * 10(-8) mol cm(-2) s(-1) has been
      obtained. The addition of known humid creep inhibitors to the gypsum samples,
      including boric acid, tartaric acid and 3,4,5-trihydroxybenzoic acid (gallic
      acid), was found to have little measurable effect on the dissolution kinetics of
      gypsum: all yielded dissolution fluxes of 1.4 (+/-0.6) * 10(-8) mol cm(-2) s(-1).
      However, trisodium trimetaphosphate (STMP) was found to have a small detectable
      inhibitory effect relative to pure gypsum yielding a flux of 7.4 (+/-2.0) * 10(
      9) mol cm(-2) s(-1). The data strongly suggest that models for humid creep
      inhibition that involve dissolution-crystallization of gypsum crystallites are
      less likely than those that involve a hindered ingress of water into the gypsum
      matrix. For comparison, composite materials that comprised of calcium sulfate
      anhydrite (CaSO(4)) crystallites bound by a polyphosphate matrix were also
      studied. For some of these samples, Ca(2+) surface fluxes were observed to be ~1
      order of magnitude lower than values for polycrystalline gypsum control
      substrates, suggesting a useful way to impart water resistance to gypsum-based
      materials.

PMID- 21861514
TI  - Anharmonic vibrational modes of nucleic acid bases revealed by 2D IR
      spectroscopy.
AB  - Polarization-dependent two-dimensional infrared (2D IR) spectra of the purine and
      pyrimadine base vibrations of five nucleotide monophosphates (NMPs) were acquired
      in D(2)O at neutral pH in the frequency range 1500-1700 cm(-1). The distinctive
      cross-peaks between the ring deformations and carbonyl stretches of NMPs indicate
      that these vibrational modes are highly coupled, in contrast with the traditional
      peak assignment, which is based on a simple local mode picture such as C?O, C?N,
      and C?C double bond stretches. A model of multiple anharmonically coupled
      oscillators was employed to characterize the transition energies, vibrational
      anharmonicities and couplings, and transition dipole strengths and orientations.
      No simple or intuitive structural correlations are found to readily assign the
      spectral features, except in the case of guanine and cytosine, which contain a
      single local CO stretching mode. To help interpret the nature of these
      vibrational modes, we performed density functional theory (DFT) calculations and
      found that multiple ring vibrations are coupled and delocalized over the purine
      and pyrimidine rings. Generally, there is close correspondence between the
      experimental and computational results, provided that the DFT calculations
      include explicit waters solvating hydrogen-bonding sites. These results provide
      direct experimental evidence of the delocalized nature of the nucleotide base
      vibrations via a nonperturbative fashion and will serve as building blocks for
      constructing a structure-based model of DNA and RNA vibrational spectroscopy.

PMID- 21861515
TI  - Origin of ultrafast excited state dynamics of 1-nitropyrene.
AB  - Time-resolved emission measurements in subpicosecond time domain have been
      carried out for 1-nitropyrene in different solvents to understand the mechanism
      for the observed ultrafast decay of its first excited singlet state. Excited
      state dynamics of 1-nitropyrene is found to be independent of the solvent
      viscosity. This result contradicts the proposition in the literature (J. Phys.
      Chem. A 2007, 111, 552) that the ultrafast decay in 1-nitropyrene is due to the
      large amplitude torsional motion of the nitro group around the pyrene moiety.
      Excited-state dynamics of 1-nitropyrene in solvents with different dielectric
      constants shows that excited-state lifetime suddenly increases after a certain
      value of the dielectric constant. Detailed quantum chemical calculations have
      been carried out to understand the process that is responsible for the observed
      effect of the dielectric constant on the excited-state dynamics of 1-nitropyrene.
      It is seen that the excited-state lifetime and the singlet-triplet energy gap
      follow similar variation with the dielectric constant of the medium. Such a
      correlation between the excited-state lifetime and the singlet-triplet energy gap
      supports the fact that the observed ultrafast decay for 1-nitropyrene is due to
      an efficient intersystem crossing rather than to the torsional motion of the
      nitro group as proposed in the literature.

PMID- 21861516
TI  - Influence of patterned concave depth and surface curvature on anodization of
      titania nanotubes and alumina nanopores.
AB  - Vertically aligned TiO(2) nanotube and Al(2)O(3) nanopore arrays have been
      obtained by pattern guided anodization with uniform concave depths. There are
      some studies about the effect of surface curvature on the growth of Al(2)O(3)
      nanopores. However, the surface curvature influence on the development of TiO(2)
      nanotubes is seldom studied. Moreover, there is no research about the effect of
      heterogeneous concave depths of the guiding patterns on the anodized TiO(2)
      nanotube and Al(2)O(3) nanopore characteristics, such as diameter, growth
      direction, and termination/bifurcation. In this study, focused ion beam
      lithography is used to create concave patterns with heterogeneous depths on flat
      surfaces and with uniform depths on curved surfaces. For the former, bending and
      bifurcation of nanotubes/nanopores are observed after the anodization. For the
      latter, bifurcation of a large tube into two smaller tubes occurs on concave
      surfaces, while termination of existing tubes occurs on convex surfaces. The
      growth direction of all TiO(2) nanotubes is perpendicular to the local surface
      and thus is different on different facets of the same Ti foil. At the edge of the
      Ti foil where two facets meet, the nanotube growth direction is bent, resulting
      in a large stress release that causes the formation of cracks.

PMID- 21861517
TI  - Patterned surface derivatization using Diels-Alder photoclick reaction.
AB  - The utility of photochemically induced hetero-Diels-Alder reaction for the light
      directed surface derivatization and patterning was demonstrated. Glass slides
      functionalized with vinyl ether moieties are covered with aqueous solution of
      substrates conjugated to 3-(hydroxymethyl)-2-naphthol (NQMP). Subsequent
      irradiation via shadow mask results in an efficient conversion of the latter
      functionality into reactive 2-napthoquinone-3-methide (oNQM) in the exposed
      areas. oNQM undergoes very facile hetero Diels-Alder addition (k(D-A) ~ 4 * 10(4)
      M(-1)s(-1)) to immobilized vinyl ether molecules resulting in a photochemically
      stable covalent link between a substrate and a surface. Unreacted oNQM groups are
      rapidly hydrated to regenerate NQMP. The click chemistry based on the addition of
      photochemically generated oNQM to vinyl ether works well in aqueous solution,
      proceeds at high rate under ambient conditions, and does not require catalyst or
      additional reagents. This photoclick strategy represents an unusual paradigm in
      photopatterning: the surface itself is photochemically inert, while photoreactive
      component is present in the solution. The short lifetime (tau ~ 7 ms in H(2)O) of
      the active form of a photoclick reagent in aqueous solution prevents its
      migration from the site of irradiation, thus allowing for the spatial control of
      surface derivatization. Both o-napthoquinone methide precursors and vinyl ethers
      are stable in dark and the reaction is orthogonal to other derivatization
      techniques, such as acetylene-azide click reaction.

PMID- 21861518
TI  - Biogenesis of the unique 4',5'-dehydronucleoside of the uridyl peptide antibiotic
      pacidamycin.
AB  - The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that
      act by inhibiting the clinically unexploited target translocase I, a key enzyme
      in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin
      4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that
      the biosynthesis of the pacidamycin nucleoside in  Streptomyces coeruleorubidus 
      proceeds through three steps from uridine. The transformations involve oxidation
      of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and
      dehydration by the Cupin-domain protein Pac13.

PMID- 21861519
TI  - Aggregation-induced amplified quenching in conjugated polyelectrolytes with
      interrupted conjugation.
AB  - A pair of anionic conjugated polyelectrolytes that contain three-ring (phenylene
      ethynylene) units linked by a single -CH(2)- or -O- tether (P1 and P2,
      respectively) are studied. The linkers serve to interrupt the pi conjugation
      along the polymer backbone. Fluorescence spectroscopy reveals that P2 forms a
      fluorescent aggregate in methanol and water; however, the fluorescence of P1 is
      much weaker in water, and P1 exhibits only weak aggregate fluorescence.
      Fluorescence quenching of the polymers was examined using methyl viologen
      (MV(2+)) as a cationic quencher. P1 shows only a weak amplified quenching effect,
      with a Stern-Volmer quenching constant of K(SV) ~ 6 * 10(5) M(-1) in methanol.
      Interestingly, for P2 in methanol, the aggregate emission is strongly quenched
      with K(SV) ~ 5 * 10(6) M(-1), which is comparable to the highest quenching
      efficiency observed for fully pi-conjugated polyelectrolytes. By contrast, the
      monomer emission is quenched much less efficiently, with K(SV) ~ 2 * 10(5) M(-1).
      The results are explained by a model in which -O- linked polymer P2 is able to
      fold into a helical conformation in solution, which facilitates the formation of
      extended pi-stacked aggregates allowing long-distance exciton transport.

PMID- 21861520
TI  - Total syntheses of drimane-type sesquiterpenoids enabled by a gold-catalyzed
      tandem reaction.
AB  - Development of a gold-catalyzed tandem reaction of 1,7-diynes with both internal
      and external nucleophiles was realized, which constructed five chemical bonds,
      two rings, and two stereogenic centers in a single step. Based on the novel
      cascade transformation, we achieved a unified strategy toward the stereoselective
      total syntheses of C-15 oxygenated drimane-type sesquiterpenoids and their
      analogues, which provided the natural products kuehneromycin A, antrocin,
      anhydromarasmone, and marasmene as a proof-of-concept study.

PMID- 21861521
TI  - Morphology design of porous coordination polymer crystals by coordination
      modulation.
AB  - The design of crystal morphology, or exposed crystal facets, has enabled the
      development (e.g., catalytic activities, material attributes, and oriented film
      formation) of porous coordination polymers (PCPs) without changing material
      compositions. However, because crystal growth mechanisms are not fully
      understood, control of crystal morphology still remains challenging. Herein, we
      report the morphology design of [Cu(3)(btc)(2)](n) (btc = benzene-1,3,5
      tricarboxylate) by the coordination modulation method (modulator = n-dodecanoic
      acid or lauric acid). A morphological transition (octahedron-cuboctahedron-cube)
      in the [Cu(3)(btc)(2)](n) crystal was observed with an increase in concentration
      of the modulator. By suitably defining a coarse-grained standard unit of
      [Cu(3)(btc)(2)](n) as its cuboctahedron main pore and determining its attachment
      energy on crystal surfaces, Monte Carlo coarse-grain modeling revealed the
      population and orientation of carboxylates and elucidated an important role of
      the modulator in determining the <100>- and <111>-growth throughout the crystal
      growth process. This comprehension, in fact, successfully led to designed crystal
      morphologies with oriented growth on bare substrates. Because selective crystal
      orientations on the bare substrates were governed by crystal morphology, this
      contribution also casts a new light on the unexplored issue of the significance
      of morphology design of PCPs.

PMID- 21861523
TI  - Protective effect of Monascus-fermented red mold rice against alcoholic liver
      disease by attenuating oxidative stress and inflammatory response.
AB  - Monascus purpureus NTU 568 fermented rice is reported to exhibit a wide variety
      of biological effects, including antitumor, antihypertriglyceridemia,
      antioxidant, and anti-inflammatory activities. However, its role in the
      pathogenesis of alcoholic liver disease remains obscure. In this study, the
      hepatoprotective effects of Monascus-fermented red mold rice (RMR) was evaluated
      in vivo using chronic alcohol-induced mice as an experimental model. The alcohol
      induced mice were orally treated with RMR at 307.5 mg/kg (1-fold), 615 mg/kg (2
      fold), and 1537.5 mg/kg (5-fold) for 5 weeks, whereas controls received vehicle
      only. Treatment with RMR significantly attenuated the increased level of serum
      transaminases (aspartate aminotransferase and alanine aminotransferase) and
      hepatic triglyceride and total cholesterol accumulation. Furthermore, RMR
      elevates hepatic antioxidant ability that reduced hepatic cell damage (steatosis)
      and decreased tissue inflammatory cytokine levels. These findings suggest that
      Monascus-fermented RMR may represent a novel, protective strategy against
      alcoholic liver disease by attenuating oxidative stress, inflammatory response,
      and steatosis.

PMID- 21861524
TI  - Infrared spectra of the C2H2-(OCS)2 van der Waals complex: observation of a
      structure with C2 symmetry.
AB  - Infrared spectra of the C(2)H(2)-(OCS)(2) trimer are studied by means of direct
      infrared absorption spectroscopy. The van der Waals complexes are generated in a
      supersonic slit-jet apparatus and probed using a rapid-scan tunable diode laser
      in the region of the nu(1) fundamental vibration of the OCS monomer. Two infrared
      bands are analyzed for the lowest energy isomer of the trimer, which has C(2)
      symmetry and is experimentally observed here for the first time. A relatively
      strong band centered at 2068.93 cm(-1) is assigned as the out-of-phase vibrations
      of the pair of equivalent OCS monomers. This band is blue-shifted relative to the
      free OCS monomer but with a reduced shift as compared with the analogous
      vibration of the nonpolar OCS dimer. A weaker red-shifted band observed at
      2049.64 cm(-1) establishes the nonplanarity of the OCS dimer subunit within the
      trimer. Spectra for three isotopologues in addition to the normal form are used
      to help define an experimental structure, which agrees well with past and present
      semiempirical calculations.

PMID- 21861522
TI  - Enantioselective total syntheses of (-)-palau'amine, (-)-axinellamines, and (-)
      massadines.
AB  - Dimeric pyrrole-imidazole alkaloids represent a rich and topologically unique
      class of marine natural products. This full account will follow the progression
      of efforts that culminated in the enantioselective total syntheses of the most
      structurally ornate members of this family: the axinellamines, the massadines,
      and palau'amine. A bio-inspired approach capitalizing on the pseudo-symmetry of
      the members of this class is recounted, delivering a deschloro derivative of the
      natural product core. Next, the enantioselective synthesis of the
      chlorocyclopentane core featuring a scalable, catalytic, enantioselective Diels
      Alder reaction of a 1-siloxydiene is outlined in detail. Finally, the successful
      divergent conversion of this core to each of the aforementioned natural products,
      and the ensuing methodological developments, are described.

PMID- 21861525
TI  - Preface: forum on biocidal materials & interfaces.

PMID- 21861526
TI  - Chemical mechanisms in biochemical reactions.

PMID- 21861527
TI  - Preferential binding of peptides to graphene edges and planes.
AB  - Peptides identified from combinatorial peptide libraries have been shown to bind
      to a variety of abiotic surfaces. Biotic-abiotic interactions can be exploited to
      create hybrid materials with interesting electronic, optical, or catalytic
      properties. Here we show that peptides identified from a combinatorial phage
      display peptide library assemble preferentially to the edge or planar surface of
      graphene and can affect the electronic properties of graphene. Molecular dynamics
      simulations and experiments provide insight into the mechanism of peptide binding
      to the graphene edge.

PMID- 21861528
TI  - Infrared photodissociation spectroscopy of copper carbonyl cations.
AB  - Copper carbonyl cations of the form Cu(CO)(n)(+) (n = 1-8) are produced in a
      molecular beam via laser vaporization in a pulsed nozzle source. Mass-selected
      infrared photodissociation spectroscopy in the carbonyl stretching region is used
      to study these ions and their argon "tagged" analogues. The geometries and
      electronic states of these complexes are determined by the number of infrared
      active bands, their frequency positions, and their relative intensities compared
      to the predictions of theory. Cu(CO)(4)(+) has a completed coordination sphere,
      consistent with its expected 18-electron stability. It also has a tetrahedral
      structure similar to that of its neutral isoelectronic analog Ni(CO)(4). The
      carbonyl stretch in Cu(CO)(4)(+) (2198 cm(-1)) is blue-shifted with respect to
      the free CO vibration (2143 cm(-1)), providing evidence that this is a "non
      classical" metal carbonyl.

PMID- 21861529
TI  - Competitive and synergistic effects in pH dependent phosphate adsorption in
      soils: LCD modeling.
AB  - The pH dependency of soluble phosphate in soil was measured for six agricultural
      soils over a pH range of 3-10. A mechanistic model, the LCD (ligand charge
      distribution) model, was used to simulate this change, which considers phosphate
      adsorption to metal (hydr)oxides in soils under the influence of natural organic
      matter (NOM) and polyvalent cations (Ca(2+), Al(3+), and Fe(3+)). For all soils
      except one, the description in the normal pH range 5-8 is good. For some soils at
      more extreme pH values (for low P-loading soils at low pH and for high P-loading
      soils at high pH), the model over predicts soluble P. The calculation shows that
      adsorption is the major mechanism controlling phosphate solubility in soils,
      except at high pH in high P-loading soils where precipitation of calcium
      phosphate may take place. NOM and polyvalent cations have a very strong effect on
      the concentration level of P. The pattern of pH dependency of soluble P in soils
      differs greatly from the pH effects on phosphate adsorption to synthetic metal
      (hydr)oxides in a monocomponent system. According to the LCD model, the pH
      dependency in soil is mainly caused by the synergistic effects of Ca(2+)
      adsorption to oxides. Adsorption of Al(3+) to NOM adsorbed plays an important
      role only at a pH < 4.5. Presence of NOM coating strongly competes with phosphate
      for the adsorption and is an important factor to consider in modeling phosphate
      adsorption in natural samples.

PMID- 21861530
TI  - Mesoporous layer-by-layer ordered nanohybrids of layered double hydroxide and
      layered metal oxide: highly active visible light photocatalysts with improved
      chemical stability.
AB  - Mesoporous layer-by-layer ordered nanohybrids highly active for visible light
      induced O(2) generation are synthesized by self-assembly between oppositely
      charged 2D nanosheets of Zn-Cr-layered double hydroxide (Zn-Cr-LDH) and layered
      titanium oxide. The layer-by-layer ordering of two kinds of 2D nanosheets is
      evidenced by powder X-ray diffraction and cross-sectional high resolution
      transmission electron microscopy. Upon the interstratification process, the
      original in-plane atomic arrangements and electronic structures of the component
      nanosheets remain intact. The obtained heterolayered nanohybrids show a strong
      absorption of visible light and a remarkably depressed photoluminescence signal,
      indicating an effective electronic coupling between the two component nanosheets.
      The self-assembly between 2D inorganic nanosheets leads to the formation of
      highly porous stacking structure, whose porosity is controllable by changing the
      ratio of layered titanate/Zn-Cr-LDH. The resultant heterolayered nanohybrids are
      fairly active for visible light-induced O(2) generation with a rate of ~1.18 mmol
      h(-1) g(-1), which is higher than the O(2) production rate (~0.67 mmol h(-1) g(
      1)) by the pristine Zn-Cr-LDH material, that is, one of the most effective
      visible light photocatalysts for O(2) production, under the same experimental
      condition. This result highlights an excellent functionality of the Zn-Cr-LDH
      layered titanate nanohybrids as efficient visible light active photocatalysts. Of
      prime interest is that the chemical stability of the Zn-Cr-LDH is significantly
      improved upon the hybridization, a result of the protection of the LDH lattice by
      highly stable titanate layer. The present findings clearly demonstrate that the
      layer-by-layer-ordered assembly between inorganic 2D nanosheets is quite
      effective not only in improving the photocatalytic activity of the component
      semiconductors but also in synthesizing novel porous LDH-based hybrid materials
      with improved chemical stability.

PMID- 21861532
TI  - New method for affinity adsorbent screening using gold colloids.
AB  - A rapid, effective method for the screening of adsorbent ligands based on the
      unique optical properties of gold colloid has been developed. Different
      interactions between adsorbate and ligands induce different states of aggregation
      of the gold colloid, and the associated distinct color changes of the colloid
      have been utilized to estimate the affinity of the ligands toward the adsorbate.
      In this work, phosphorylated peptide CGGFGGpSG was appended to a gold colloid to
      obtain the adsorbate-modified gold colloid (CG8-AuNPs). Candidate ligands Dpa
      Zn(2+), DMAPAA, and AAn were copolymerized with acrylamide to form linear
      polymers and cross-linked CG8-AuNPs to induce aggregation. Screening of the
      candidate ligands revealed that Dpa-Zn(2+) showed the highest affinity among
      those tested, inducing a color change of the gold colloid at a concentration of
      10 MUM, which is much lower than those of ligands DMAPAA (40 MUM) and AAn (almost
      no color change could be observed). Subsequent statistical adsorption experiments
      confirmed these screening results, with the adsorbent A-AAm-Dpa-Zn(2+) showing
      the highest adsorption capacity (426 mg/g) for CG-8, almost twice that of
      adsorbent A-AAm-DMAPAA. This reported method has low sample consumption, and the
      screening may be simply monitored by the naked eye.

PMID- 21861531
TI  - Extraordinarily robust polyproline type I peptoid helices generated via the
      incorporation of alpha-chiral aromatic N-1-naphthylethyl side chains.
AB  - Peptoids, or oligomers of N-substituted glycines, are a class of foldamers that
      have shown extraordinary functional potential since their inception nearly two
      decades ago. However, the generation of well-defined peptoid secondary structures
      remains a difficult task. This challenge is due, in part, to the lack of a
      thorough understanding of peptoid sequence-structure relationships and,
      consequently, an incomplete understanding of the peptoid folding process. We seek
      to delineate sequence-structure relationships through the systematic study of
      noncovalent interactions in peptoids and the design of novel amide side chains
      capable of such interactions. Herein, we report the synthesis and detailed
      structural analysis of a series of (S)-N-(1-naphthylethyl)glycine (Ns1npe)
      peptoid homo-oligomers by X-ray crystallography, NMR spectroscopy, and circular
      dichroism (CD) spectroscopy. Four of these peptoids were found to adopt well
      defined structures in the solid state, with dihedral angles similar to those
      observed in polyproline type I (PPI) peptide helices and in peptoids with alpha
      chiral side chains. The X-ray crystal structure of a representative Ns1npe
      tetramer revealed an all cis-amide helix, with approximately three residues per
      turn, and a helical pitch of approximately 6.0 A. 2D-NMR analysis of the length
      dependent Ns1npe series showed that these peptoids have very high overall
      backbone amide K(cis/trans) values in acetonitrile, indicative of
      conformationally homogeneous structures in solution. Additionally, CD
      spectroscopy studies of the Ns1npe homo-oligomers in acetonitrile and methanol
      revealed a striking length-dependent increase in ellipticity per amide. These
      Ns1npe helices represent the most robust peptoid helices to be reported, and the
      incorporation of (S)-N-(1-naphthylethyl)glycines provides a new approach for the
      generation of stable helical structure in this important class of foldamers.

PMID- 21861533
TI  - 4-methylcatechol inhibits protein oxidation in meat but not disulfide formation.
AB  - The interaction between phenolic compounds and protein thiols was investigated in
      minced beef with or without 500 ppm 4-methylcatechol (4-MC) that had been stored
      under oxygen or argon for 7 days (4  degrees C). Myofibrillar protein isolates
      were extracted, and the oxidative stability evaluated by the protein radical
      intensity measured by ESR spectroscopy was found to be improved by 4-MC as well
      as by storage without oxygen. Significant loss of thiols was found in samples
      stored under oxygen compared to argon, whereas an additional loss was found in
      samples with added 4-MC stored under oxygen. In beef with added 4-MC, LC-MS
      analysis showed formation of thiol-quinone adducts, which may explain the
      observed additional loss of thiols. Although storage without oxygen inhibited
      protein cross-link formation as evaluated by SDS-PAGE, both in presence and in
      the absence of 4-MC, no inhibitory effect of 4-MC was found on the formation of
      protein disulfide cross-links in beef stored under oxygen.

PMID- 21861534
TI  - Mass spectrometry-based proteomics of human cannabinoid receptor 2: covalent
      cysteine 6.47(257)-ligand interaction affording megagonist receptor activation.
AB  - The lack of experimental characterization of the structures and ligand-binding
      motifs of therapeutic G-protein coupled receptors (GPCRs) hampers rational drug
      discovery. The human cannabinoid receptor 2 (hCB2R) is a class-A GPCR and
      promising therapeutic target for small-molecule cannabinergic agonists as
      medicines. Prior mutational and modeling data constitute provisional evidence
      that AM-841, a high-affinity classical cannabinoid, interacts with cysteine
      C6.47(257) in hCB2R transmembrane helix 6 (TMH6) to afford improved hCB2R
      selectivity and unprecedented agonist potency. We now apply bottom-up mass
      spectrometry (MS)-based proteomics to define directly the hCB2R-AM-841
      interaction at the amino-acid level. Recombinant hCB2R, overexpressed as an N
      terminal FLAG-tagged/C-terminal 6His-tagged protein (FLAG-hCB2R-6His) with a
      baculovirus system, was solubilized and purified by immunochromatography as
      functional receptor. A multiplex multiple reaction monitoring (MRM)-MS method was
      developed that allowed us to observe unambiguously all seven discrete TMH
      peptides in the tryptic digest of purified FLAG-hCB2R-6His and demonstrate that
      AM-841 modifies hCB2R TMH6 exclusively. High-resolution mass spectra of the TMH6
      tryptic peptide obtained by Q-TOF MS/MS analysis demonstrated that AM-841
      covalently and selectively modifies hCB2R at TMH6 cysteine C6.47(257). These data
      demonstrate how integration of MS-based proteomics into a ligand-assisted protein
      structure (LAPS) experimental paradigm can offer guidance to structure-enabled
      GPCR agonist design.

PMID- 21861535
TI  - Tunable photoconduction sensitivity and bandwidth for lithographically patterned
      nanocrystalline cadmium selenide nanowires.
AB  - Nanocrystalline cadmium selenide (nc-CdSe) nanowires were prepared using the
      lithographically patterned nanowire electrodeposition method. Arrays of 350
      linear nc-CdSe nanowires with lateral dimensions of 60 nm (h) * 200 nm (w) were
      patterned at 5 MUm pitch on glass. nc-CdSe nanowires electrodeposited from
      aqueous solutions at 25  degrees C had a mean grain diameter, d(ave), of 5 nm. A
      combination of three methods was used to increase d(ave) to 10, 20, and 100 nm:
      (1) The deposition bath was heated to 75  degrees C, (2) nanowires were thermally
      annealed at 300  degrees C, and (3) nanowires were exposed to methanolic CdCl(2)
      followed by thermal annealing at 300  degrees C. The morphology, chemical
      composition, grain diameter, and photoconductivity of the resulting nanowires
      were studied as a function of d(ave). As d(ave) was increased from 10 to 100 nm,
      the photoconductivity response of the nanowires was modified in two ways: First,
      the measured photoconductive gain, G, was elevated from G = 0.017 (d(ave) = 5 nm)
      to ~4.9 (100 nm), a factor of 290. Second, the photocurrent rise time was
      increased from 8 MUs for d(ave) = 10 nm to 8 s for 100 nm, corresponding to a
      decrease by a factor of 1 million of the photoconduction bandwidth from 44 kHz to
      44 mHz.

PMID- 21861536
TI  - Collapse and recovery of green fluorescent protein chromophore emission through
      topological effects.
AB  - Housed within the 11-stranded beta-barrel of the green fluorescent protein (GFP)
      is the arylideneimidazolidinone (AMI) chromophore, the component responsible for
      fluorescence. This class of small-molecule chromophore has drawn significant
      attention for its remarkable photophysical and photochemical properties, both
      within the intact protein and after its denaturation. All of the proteins so far
      isolated that have visible light fluorescence have been found to contain an AMI
      chromophore. These proteins comprise an extensive rainbow, ranging from GFP,
      which contains the simplest chromophore, p-hydroxybenzylideneimidazolidinone (p
      HOBDI), to proteins having molecules with longer conjugation lengths and a
      variety of intraprotein interactions. The fluorescence invariably almost vanishes
      upon removal of the protective beta-barrel. The role of the barrel in hindering
      internal conversion has been the subject of numerous studies, especially in our
      laboratories and those of our collaborators. A better understanding of these
      chromophores has been facilitated by the development of numerous synthetic
      protocols. These syntheses, which commonly use the Erlenmeyer azlactone method,
      have evolved in recent years with the development of a [2 + 3] cycloaddition
      exploited in our laboratory. The synthetic AMI chromophores have allowed
      delineation of the complex photophysics of GFP and its derivatives. Upon
      denaturation, AMI chromophores are marked by 4 orders of magnitude of diminution
      in emission quantum yield (EQY). This result is attributed to internal conversion
      resulting from conformational freedom in the released chromophore, which is not
      allowed within the restrictive beta-barrel. To date, the photophysical properties
      of the AMI chromophore remain elusive and have been attributed to a variety of
      mechanisms, including cis-trans isomerization, triplet formation, hula twisting,
      and proton transfer. Advanced studies involving gas-phase behavior, solvent
      effects, and protonation states have significantly increased our understanding of
      the chromophore photophysics, but a comprehensive picture is only slowly
      emerging. Most importantly, mechanisms in structurally defined chromophores may
      provide clues as to the origin of the "blinking" behavior of the fluorescent
      proteins themselves. One approach to examining the effect of conformational
      freedom on rapid internal conversion of the chromophores is to restrict the
      molecules, both through structural modifications and through adjustments of the
      supramolecular systems. We thus include here a discussion of studies involving
      the crystalline state, inclusion within natural protein-binding pockets,
      complexation with metal ions, and sequestration within synthetic cavities; all of
      this research affirms the role of restricting conformational freedom in partially
      restoring the EQY. Additionally, new photochemistry is observed within these
      restricted systems. Many of the studies carried out in our laboratories show
      promise for these molecules to be adapted as molecular probes, wherein inclusion
      turns on the fluorescence and provides a signaling mechanism. In this Account, we
      present an overview of the AMI chromophores, including synthesis, overall
      photophysics, and supramolecular behavior. A significant amount of work remains
      for researchers to fully understand the properties of these chromophores, but
      important progress achieved thus far in photophysics and photochemistry is
      underscored here.

PMID- 21861538
TI  - Biosimilars of biological drug therapies: regulatory, clinical and commercial
      considerations.
AB  - Biologicals are distinct from small molecule drugs in that they are larger, more
      structurally complex agents. While the overall risk is modest, the active protein
      structure characteristic of biologicals makes them more prone to induce an acute
      and/or chronic immune response. Biosimilars are a new class of drugs intended to
      offer comparable safety and efficacy to the reference, off-patent biological.
      They are not generic alternatives per se and are generally not interchangeable.
      Given their structural complexity, multifaceted manufacturing process and risk
      for immunogenicity, unique regulatory pathways are required for biosimilars. In
      this article, we review the clinical, safety and submission requirements for
      biosimilars in several major markets. We also highlight issues of ongoing debate
      amongst key stakeholders and examine some of the commercial challenges faced by
      developers of biosimilars. As the leader of biosimilars drug approval and product
      uptake, the EU is highlighted.

PMID- 21861537
TI  - Edoxaban: a new oral direct factor xa inhibitor.
AB  - Edoxaban is an oral direct factor Xa inhibitor that is currently undergoing
      investigation in phase III clinical trials for the prevention of stroke in
      patients with atrial fibrillation (AF) and for the prevention and treatment of
      venous thromboembolic events (VTE). Factor Xa is an attractive target for
      anticoagulant treatment, as it is the primary and rate-limiting source of
      amplification in the coagulation cascade. Edoxaban is a competitive inhibitor of
      factor Xa and has >10 000-fold greater selectivity for factor Xa relative to
      thrombin. In phase I clinical trials, the anticoagulant effects of edoxaban
      included dose-dependent increases in activated partial thromboplastin time and
      prothrombin time following single edoxaban doses of 10-150 mg and after multiple
      ascending doses (60 mg twice daily, 90 mg daily and 120 mg daily). The
      anticoagulant effects of edoxaban were rapid in onset (time to peak plasma
      concentration 1-2 hours) and sustained for up to 24 hours. Prolongation of
      bleeding time in 8% of subjects was >9.5 minutes (none of which appeared to be
      clinically significant) 2 hours after initial dosing, and was independent of
      edoxaban dose, formulation or dietary state. In general, plasma edoxaban
      concentrations were linearly correlated with coagulation parameters. Phase II
      clinical trials in patients with AF and VTE suggest that the edoxaban 30 mg once
      daily and 60 mg once-daily regimens had a similar or better safety profile
      compared with dose-adjusted warfarin (international normalized ratio 2.0-3.0) in
      terms of bleeding events, and that edoxaban was not associated with
      hepatotoxicity. In addition, edoxaban was associated with statistically
      significant dose-dependent reductions in VTE after orthopaedic surgery compared
      with placebo or dalteparin sodium. Further clinical investigation of the efficacy
      and safety of once-daily edoxaban is being conducted in phase III clinical trials
      in comparison with warfarin in patients with AF in the phase III ENGAGE AF-TIMI
      48 trial (NCT00781391), and in comparison with low-molecular weight
      heparin/warfarin in the prevention of recurrent VTE in patients with symptomatic
      deep vein thrombosis and/or pulmonary embolism in the HOKUSAI VTE trial
      (NCT00986154).

PMID- 21861539
TI  - Acute myeloid leukaemia: optimal management and recent developments.
AB  - The current treatment of patients with acute myeloid leukaemia yields poor
      results, with expected cure rates in the order of 30-40% depending on the
      biological characteristics of the leukaemic clone. Therefore, new agents and
      schemas are intensively studied in order to improve patients' outcomes. This
      review summarizes some of these new paradigms, including new questions such as
      which anthracycline is most effective and at what dose. High doses of
      daunorubicin have shown better responses in young patients and are well tolerated
      in elderly patients. Monoclonal antibodies are promising agents in good risk
      patients. Drugs blocking signalling pathways could be used in combination with
      chemotherapy or in maintenance with promising results. Epigenetic therapies,
      particularly after stem cell transplantation, are also discussed. New drugs such
      as clofarabine and flavopiridol are reviewed and the results of their use
      discussed. It is clear that many new approaches are under study and hopefully
      will be able to improve on the outcomes of the commonly used '7+3' regimen of an
      anthracycline plus cytarabine with daunorubicin, which is clearly an ineffective
      therapy in the majority of patients.

PMID- 21861540
TI  - Management of recurrent head and neck cancer: recent progress and future
      directions.
AB  - The incidence of squamous cell carcinoma of the head and neck (SCCHN) is on the
      rise in the US despite a drop in cigarette smoking rates. Much of this rise is
      due to the increasing incidence of SCCHN attributable to human papillomavirus
      (HPV). HPV-related SCCHN has a high cure rate, which contributes to the stable
      death rates despite the increased incidence. Up to half of patients with SCCHN
      will develop recurrence. For these patients, the first clinical decision is
      whether the recurrence is potentially treatable for cure, or is incurable. For
      those deemed potentially curable, surgical or radiation-based therapies, or both,
      are undertaken. For those who have incurable recurrences, the goals are
      palliation and possibly prolongation of life - average survivals are in the range
      of 6-12 months depending on the type of recurrence and other factors. Several
      chemotherapy drugs are active in SCCHN, most notably the platinum compounds,
      taxanes, fluorouracil (5-FU), methotrexate and cetuximab. Approximately 10-25% of
      patients will respond to treatment with one of these drugs. The response rate is
      higher for combinations such as a platinum plus a taxane, a platinum plus 5-FU, a
      combination of the three, or one of more of these drugs plus cetuximab.
      Combination chemotherapy has not been shown to prolong survival over single-agent
      therapy, with the exception of the addition of cetuximab to a platinum and 5-FU
      combination. A number of orally bioavailable tyrosine kinase inhibitors have been
      tested or are undergoing trials in SCCHN. None of these has as yet been shown to
      be more effective than the currently available drugs. For patients with
      recurrences who are undergoing active therapy, and especially for those for whom
      further therapy is no longer appropriate or is declined, strict attention is
      necessary to palliation of pain, oral and airway issues, and to nutrition,
      speech, and social and psychological issues.

PMID- 21861541
TI  - Once- versus twice-daily tacrolimus: are the formulations truly equivalent?
AB  - Tacrolimus is a cornerstone immunosuppressant agent in the prevention of organ
      rejection following transplantation. While typically administered twice daily
      (Prograf(r)), a modified-release once-daily formulation (Advagraf(r)) has
      recently been developed and licensed for use. To date, the majority of published
      data relating to the use of Advagraf(r) have arisen from industry-sponsored
      clinical trials. These have shown that conversion from Prograf(r) to Advagraf(r)
      on a 1 mg : 1 mg basis in both stable and de novo kidney and liver transplant
      recipients yields lower peak concentrations (C(max)) but equivalent overall drug
      exposure (area under the concentration-time curve from 0 to 24 hours post-dose;
      AUC(24)) and trough concentrations (C(min)). This has led to the proposal that
      the same total daily dose, target C(min) and therapeutic drug monitoring (TDM)
      strategies can be applied irrespective of preparation. However, while Advagraf(r)
      fulfils criteria for bioequivalence according to the European Medicines Agency
      and US FDA, lower tacrolimus exposure has been observed in the majority of
      clinical studies, particularly in the early post-transplant period. This has
      resulted in a need for higher doses of Advagraf(r) compared with Prograf(r) to
      achieve similar C(min) values. Significant between-subject variability in the
      C(min)/AUC(24) relationship with Advagraf(r) has also been demonstrated,
      suggesting possible problems with TDM based on C(min) values. In non-comparative
      conversion studies, Advagraf(r) demonstrated similar efficacy and safety to
      Prograf(r). However, phase III studies in de novo kidney and liver transplant
      recipients have shown higher rates of acute rejection with Advagraf(r), possibly
      explained by the differing C(max) values achieved with the two preparations.
      While it has been suggested that once-daily administration may improve
      compliance, no studies have proven this to be the case. This article reviews the
      pharmacokinetics, efficacy, adverse effects and utility of Advagraf(r) in
      relation to its equivalence to Prograf(r), and areas that require additional
      research are identified.

PMID- 21861543
TI  - Nilotinib: in the first-line treatment of newly diagnosed Philadelphia chromosome
      positive chronic myeloid leukaemia in chronic phase.
AB  - Nilotinib is an effective first-line treatment for newly diagnosed Philadelphia
      chromosome-positive chronic myeloid leukaemia (CML) in chronic phase. It is an
      aminopyrimidine-based, high-affinity inhibitor of the tyrosine kinase activity of
      BCR-ABL. It thus decreases ABL-associated cell proliferation and kinase
      autophosphorylation. At 12 months, a significantly greater proportion of
      nilotinib 300 mg twice daily recipients experienced a major molecular response
      (primary endpoint) than those receiving imatinib 400 mg once daily, in the
      randomized, open-label, multicentre ENESTnd study in adults with newly diagnosed
      Philadelphia chromosome-positive CML in chronic phase. Moreover, a significantly
      greater proportion of nilotinib 300 mg twice daily than imatinib recipients had a
      complete molecular response at 12 months. Complete cytogenetic response rates
      were also significantly higher in the nilotinib 300 mg twice daily group than in
      the imatinib group at 12 months. Treatment differences in molecular response
      rates remained significant in an updated analysis, with data from a minimum
      follow-up of 24 months. Nilotinib 300 mg twice daily was generally well tolerated
      in the ENESTnd study. While nilotinib is associated with an increase in corrected
      QT interval (QTc), the incidence of cardiac-related adverse events in nilotinib
      recipients in the ENESTnd study was low.

PMID- 21861544
TI  - Live attenuated influenza vaccine (FluMist(r); FluenzTM): a review of its use in
      the prevention of seasonal influenza in children and adults.
AB  - Live attenuated influenza vaccine (LAIV) is an intranasally administered
      trivalent, seasonal influenza vaccine that contains three live influenza viruses
      (two type A [H1N1 and H3N2 subtypes] and one type B). LAIV was effective in
      protecting against culture-confirmed influenza caused by antigenically matched
      and/or distinct viral strains in children aged <=71 months enrolled in three
      phase III trials. LAIV was superior to trivalent inactivated influenza vaccine
      (TIV) in protecting against influenza caused by antigenically-matching viral
      strains in a multinational phase III trial in children aged 6-59 months. LAIV was
      also significantly more effective than TIV in decreasing the incidence of culture
      confirmed influenza illness in two open-label studies (in children with recurrent
      respiratory tract illnesses aged 6-71 months and in children and adolescents with
      asthma aged 6-17 years). LAIV did not differ significantly from placebo in
      preventing febrile illnesses in adults (primary endpoint) enrolled in a phase III
      trial. However, LAIV significantly reduced the incidence of febrile upper
      respiratory tract illnesses (URTI), severe febrile illnesses, febrile URTI
      related work absenteeism and healthcare provider use. In another well designed
      trial in adults, LAIV significantly reduced the incidence of symptomatic,
      laboratory-confirmed influenza compared with placebo (but not intramuscular TIV).
      LAIV was generally well tolerated in most age groups, with the majority of
      adverse events being mild to moderate in severity, and runny nose/nasal
      congestion being the most common. In a large phase III trial, LAIV, compared with
      TIV, was associated with an increased incidence of medically significant wheezing
      in vaccine-naive children aged <24 months and an increased incidence of
      hospitalization in children aged 6-11 months; LAIV is not approved for use in
      children <24 months. LAIV was not always associated with high rates of
      seroconversion/seroresponse, particularly in older children and adults, or in
      subjects with detectable levels of haemagglutination-inhibiting antibodies at
      baseline. However, LAIV did elicit mucosal (nasal) IgA antibody responses and
      strong cell-mediated immunity responses. Only one confirmed case of LAIV virus
      transmission to a placebo recipient (who did not become ill) occurred in a
      transmission study conducted in young children. The immunogenic response to LAIV
      in young healthy children was not affected by concomitant administration with
      other commonly administered childhood vaccines. In conclusion, intranasal LAIV
      seasonal influenza vaccine is effective and well tolerated in children,
      adolescents and adults. LAIV was more effective than TIV in children, although
      this advantage was not seen in adults. In the US, LAIV is indicated for the
      active immunization of healthy subjects aged 2-49 years against influenza disease
      caused by virus subtypes A and type B contained in the vaccine.

PMID- 21861546
TI  - Communication: vacuum ultraviolet laser photodissociation studies of small
      molecules by the vacuum ultraviolet laser photoionization time-sliced velocity
      mapped ion imaging method.
AB  - We demonstrate that the vacuum ultraviolet (VUV) photodissociation dynamics of
      N(2) and CO(2) can be studied using VUV photoionization with time-sliced velocity
      mapped ion imaging (VUV-PI-VMI) detection. The VUV laser light is produced by
      resonant sum frequency mixing in Kr. N(2) is used to show that when the photon
      energy of the VUV laser is above the ionization energy of an allowed transition
      of one of the product atoms it can be detected and characterized as the
      wavelength is varied. In this case a beta parameter = 0.57 for the N((2)D degrees
      ) was measured after exciting N(2)(o(1)Pi(u), v(') = 2, J(') = 2) <-
      N(2)(X(1)Sigma(g) (+), v(") = 0, J(") = 1). Studies with CO(2) show that when
      there is no allowed transition, an autoionization resonance can be used for the
      detection of a product atom. In this case it is shown for the first time that the
      O((1)D) atom is produced with CO((1)Sigma(+)) at 92.21 nm. These results indicate
      that the VUV laser photodissociation combined with the VUV-PI-VMI detection is a
      viable method for studying the one-photon photodissociation from the ground state
      of simple molecules in the extreme ultraviolet and VUV spectral regions.

PMID- 21861545
TI  - Plerixafor: a review of its use in stem-cell mobilization in patients with
      lymphoma or multiple myeloma.
AB  - Plerixafor (Mozobil(r)) is a CXCR4 chemokine receptor antagonist that is
      indicated for use in combination with granulocyte colony-stimulating factor (G
      CSF) to mobilize stem cells to the peripheral blood for collection and subsequent
      autologous stem-cell transplantation in patients who have non-Hodgkin's lymphoma
      (NHL) or multiple myeloma (MM) [US] and in patients who have lymphoma or MM and
      are poor mobilizers (EU). This article reviews the clinical efficacy and
      tolerability of subcutaneous plerixafor for stem-cell mobilization in patients
      with lymphoma or MM, as well as summarizing its pharmacological properties.
      Pharmacoeconomic analyses of plerixafor and decision-making algorithms intended
      to optimize its use are also discussed. Plerixafor plus G-CSF mobilized stem
      cells more efficiently than placebo plus G-CSF in adults with NHL or MM,
      according to the results of two randomized, double-blind, multicentre trials. In
      these trials, significantly more plerixafor plus G-CSF recipients than placebo
      plus G-CSF recipients reached primary apheresis targets in significantly fewer
      apheresis days. In the trial in patients with NHL, significantly more plerixafor
      plus G-CSF than placebo plus G-CSF recipients proceeded to transplantation.
      Results of compassionate-use studies in patients with lymphoma or MM demonstrated
      that plerixafor plus G-CSF successfully mobilized stem cells in the majority of
      patients who were poor mobilizers (i.e. sufficient CD34+ cells had not been
      collected during apheresis or apheresis had not occurred because of low
      peripheral blood CD34+ cell counts). Results of compassionate-use studies and
      additional studies in patients with lymphoma or MM also demonstrated that
      plerixafor plus G-CSF successfully mobilized stem cells in predicted poor
      mobilizers, such as heavily pretreated patients considered to be at high risk of
      mobilization failure. In addition, a small study showed mobilization with pre
      emptive plerixafor to be effective. Subcutaneous plerixafor was generally well
      tolerated during stem-cell mobilization in patients with NHL or MM; the most
      commonly occurring treatment-related adverse events in plerixafor plus G-CSF
      recipients included injection-site reactions and gastrointestinal adverse events.
      Preliminary results of a US cost-effectiveness analysis suggest that plerixafor
      plus G-CSF is a cost-saving option compared with cyclophosphamide plus G-CSF. A
      retrospective US cost analysis found no significant difference between plerixafor
      plus G-CSF and cyclophosphamide plus G-CSF recipients in the median total cost of
      initial mobilization, suggesting that the cost of plerixafor may be offset by
      increased utilization of other resources in patients receiving alternative
      mobilization regimens. Additional cost analyses examined the use of pre-emptive
      plerixafor; institutions have developed decision-making algorithms, mainly
      relating to the use of pre-emptive plerixafor, to help optimize its use. In
      conclusion, plerixafor is a valuable stem-cell mobilizer for use in combination
      with G-CSF in patients with lymphoma or MM, particularly in patients who are poor
      mobilizers or predicted poor mobilizers.

PMID- 21861547
TI  - Communication: toward ultrafast, reconfigurable logic in the nanoscale.
AB  - We propose and illustrate numerically a class of nanoscale, ultrafast logic gates
      with the further advantage of reconfigurability. Underlying the operation of the
      gates and their versatility is the concept of polarization control of the
      electromagnetic energy propagating via metal nanoparticle arrays. Specifically, a
      set of different logic gates is shown to obtain from a single metal nanoparticle
      junction by modification of the polarization properties of the input light
      sources. Implications and extensions of the gates are discussed.

PMID- 21861548
TI  - Communication: a new hybrid exchange correlation functional for band-gap
      calculations using a short-range Gaussian attenuation (Gaussian-Perdue-Burke
      Ernzerhof).
AB  - We have developed a new hybrid functional [Gaussian-Perdue-Burke-Ernzerhof (Gau
      PBE)] that is suitable for the calculation of solid state bandgaps using a
      periodic boundary condition. The characteristic of this functional is the use of
      a Gaussian attenuation scheme (Gau) to include a short-range Hartree-Fock (HF)
      exchange. This new functional can perform barrier height calculations with an
      accuracy comparable to the middle-range hybrid functional and bandgap
      calculations with an accuracy comparable to the Heyd-Scuseria-Ernzerhof (HSE)
      functional. However, the point is that the performance can be achieved using a
      Gaussian HF exchange, while the HISS functional calculates twice HF-exchange
      integrations using an error function to obtain both performances. In addition,
      Gau-PBE functional can decrease the time cost of bandgap calculations by an
      average of 40% compared to the HSE functional.

PMID- 21861549
TI  - Communication: configuration interaction singles has a large systematic bias
      against charge-transfer states.
AB  - We show that standard configuration interaction singles (CIS) has a systematic
      bias against charge-transfer (CT) states, wherein the computed vertical
      excitation energies for CT states are disproportionately too high (by >1 eV) as
      compared with non-CT states. We demonstrate this bias empirically for a set of
      chemical problems with both inter- and intra-molecular electron transfer, and
      then, for a small analytical model, we prove that this large difference in
      accuracy stems from the massive changes in electronic structure that must
      accompany long-range charge transfer. Thus far, the conclusion from this research
      is that, even in the context of wave function theory, CIS alone is insufficient
      for offering a balanced description of excited state surfaces (both CT and non
      CT) and explicit electron-electron correlation must be included additionally
      (e.g., via CIS(D)) for charge-transfer applications.

PMID- 21861550
TI  - Second-order nonadiabatic couplings from time-dependent density functional
      theory: evaluation in the immediate vicinity of Jahn-Teller/Renner-Teller
      intersections.
AB  - For a rigorous quantum simulation of nonadiabatic dynamics of electrons and
      nuclei, knowledge of not only the first-order but also the second-order
      nonadiabatic couplings (NACs) is required. Here, we propose a method to
      efficiently calculate the second-order NAC from time-dependent density functional
      theory (TDDFT), on the basis of the Casida ansatz adapted for the computation of
      first-order NAC, which has been justified in our previous work and can be shown
      to be valid for calculating second-order NAC between ground state and singly
      excited states within the Tamm-Dancoff approximation. Test calculations of the
      second-order NAC in the immediate vicinity of Jahn-Teller and Renner-Teller
      intersections show that calculation results from TDDFT, combined with modified
      linear response theory, agree well with the prediction from the Jahn
      Teller/Renner-Teller models. Contrary to the diverging behavior of the first
      order NAC near all types of intersection points, the Cartesian components of the
      second-order NAC are shown to be negligibly small near Renner-Teller glancing
      intersections, while they are significantly large near the Jahn-Teller conical
      intersections. Nevertheless, the components of the second-order NAC can cancel
      each other to a large extent in Jahn-Teller systems, indicating the background of
      neglecting the second-order NAC in practical dynamics simulations. On the other
      hand, it is shown that such a cancellation becomes less effective in an elliptic
      Jahn-Teller system and thus the role of second-order NAC needs to be evaluated in
      the rigorous framework. Our study shows that TDDFT is promising to provide
      accurate data of NAC for full quantum mechanical simulation of nonadiabatic
      processes.

PMID- 21861551
TI  - Wave front-ray synthesis for solving the multidimensional quantum Hamilton-Jacobi
      equation.
AB  - A Cauchy initial-value approach to the complex-valued quantum Hamilton-Jacobi
      equation (QHJE) is investigated for multidimensional systems. In this approach,
      ray segments foliate configuration space which is laminated by surfaces of
      constant action. The QHJE incorporates all quantum effects through a term
      involving the divergence of the quantum momentum function (QMF). The divergence
      term may be expressed as a sum of two terms, one involving displacement along the
      ray and the other incorporating the local curvature of the action surface. It is
      shown that curvature of the wave front may be computed from coefficients of the
      first and second fundamental forms from differential geometry that are associated
      with the surface. Using the expression for the divergence, the QHJE becomes a
      Riccati-type ordinary differential equation (ODE) for the complex-valued QMF,
      which is parametrized by the arc length along the ray. In order to integrate over
      possible singularities in the QMF, a stable and accurate Mobius propagator is
      introduced. This method is then used to evolve rays and wave fronts for four
      systems in two and three dimensions. From the QMF along each ray, the wave
      function can be easily computed. Computational difficulties that may arise are
      described and some ways to circumvent them are presented.

PMID- 21861552
TI  - Non-hard sphere thermodynamic perturbation theory.
AB  - A non-hard sphere (HS) perturbation scheme, recently advanced by the present
      author, is elaborated for several technical matters, which are key mathematical
      details for implementation of the non-HS perturbation scheme in a coupling
      parameter expansion (CPE) thermodynamic perturbation framework. NVT-Monte Carlo
      simulation is carried out for a generalized Lennard-Jones (LJ) 2n-n potential to
      obtain routine thermodynamic quantities such as excess internal energy, pressure,
      excess chemical potential, excess Helmholtz free energy, and excess constant
      volume heat capacity. Then, these new simulation data, and available simulation
      data in literatures about a hard core attractive Yukawa fluid and a Sutherland
      fluid, are used to test the non-HS CPE 3rd-order thermodynamic perturbation
      theory (TPT) and give a comparison between the non-HS CPE 3rd-order TPT and other
      theoretical approaches. It is indicated that the non-HS CPE 3rd-order TPT is
      superior to other traditional TPT such as van der Waals/HS (vdW/HS), perturbation
      theory 2 (PT2)/HS, and vdW/Yukawa (vdW/Y) theory or analytical equation of state
      such as mean spherical approximation (MSA)-equation of state and is at least
      comparable to several currently the most accurate Ornstein-Zernike integral
      equation theories. It is discovered that three technical issues, i.e., opening up
      new bridge function approximation for the reference potential, choosing proper
      reference potential, and/or using proper thermodynamic route for calculation of
      f(ex-ref), chiefly decide the quality of the non-HS CPE TPT. Considering that the
      non-HS perturbation scheme applies for a wide variety of model fluids, and its
      implementation in the CPE thermodynamic perturbation framework is amenable to
      high-order truncation, the non-HS CPE 3rd-order or higher order TPT will be more
      promising once the above-mentioned three technological advances are established.

PMID- 21861553
TI  - Open-shell reduced density matrix functional theory.
AB  - Open-shell reduced density matrix functional theory is established by
      investigating the domain of the exact functional. For spin states that are the
      ground state, a particularly simple set is found to be the domain. It cannot be
      generalized to other spin states. A number of conditions satisfied by the exact
      density matrix functional is formulated and tested for approximate functionals.
      The exact functional does not suffer from fractional spin error, which is the
      source of the static correlation error in dissociated molecules. We prove that a
      simple approximation (called the Buijse-Baerends functional, Muller or square
      root functional) has a non-positive fractional spin error. In the case of the H
      atom the error is zero. Numerical results for a few atoms are given for
      approximate density and density matrix functionals as well as a recently
      developed range-separated combination of both.

PMID- 21861554
TI  - An O(N3) implementation of Hedin's GW approximation for molecules.
AB  - We describe an implementation of Hedin's GW approximation for molecules and
      clusters, the complexity of which scales as O(N(3)) with the number of atoms. Our
      method is guided by two strategies: (i) to respect the locality of the underlying
      electronic interactions and (ii) to avoid the singularities of Green's functions
      by manipulating, instead, their spectral functions using fast Fourier transform
      methods. To take into account the locality of the electronic interactions, we use
      a local basis of atomic orbitals and, also, a local basis in the space of their
      products. We further compress the screened Coulomb interaction into a space of
      lower dimensions for speed and to reduce memory requirements. The improved
      scaling of our method with respect to most of the published methodologies should
      facilitate GW calculations for large systems. Our implementation is intended as a
      step forward towards the goal of predicting, prior to their synthesis, the
      ionization energies and electron affinities of the large molecules that serve as
      constituents of organic semiconductors.

PMID- 21861555
TI  - Direct simulation of electron transfer using ring polymer molecular dynamics:
      comparison with semiclassical instanton theory and exact quantum methods.
AB  - The use of ring polymer molecular dynamics (RPMD) for the direct simulation of
      electron transfer (ET) reaction dynamics is analyzed in the context of Marcus
      theory, semiclassical instanton theory, and exact quantum dynamics approaches.
      For both fully atomistic and system-bath representations of condensed-phase ET,
      we demonstrate that RPMD accurately predicts both ET reaction rates and
      mechanisms throughout the normal and activationless regimes of the thermodynamic
      driving force. Analysis of the ensemble of reactive RPMD trajectories reveals the
      solvent reorganization mechanism for ET that is anticipated in the Marcus rate
      theory, and the accuracy of the RPMD rate calculation is understood in terms of
      its exact description of statistical fluctuations and its formal connection to
      semiclassical instanton theory for deep-tunneling processes. In the inverted
      regime of the thermodynamic driving force, neither RPMD nor a related formulation
      of semiclassical instanton theory capture the characteristic turnover in the
      reaction rate; comparison with exact quantum dynamics simulations reveals that
      these methods provide inadequate quantization of the real-time electronic-state
      dynamics in the inverted regime.

PMID- 21861556
TI  - Local explicitly correlated second-order Moller-Plesset perturbation theory with
      pair natural orbitals.
AB  - We explore using a pair natural orbital analysis of approximate first-order pair
      functions as means to truncate the space of both virtual and complementary
      auxiliary orbitals in the context of explicitly correlated F12 methods using
      localised occupied orbitals. We demonstrate that this offers an attractive
      procedure and that only 10-40 virtual orbitals per significant pair are required
      to obtain second-order valence correlation energies to within 1-2% of the basis
      set limit. Moreover, for this level of virtual truncation, only 10-40
      complementary auxiliary orbitals per pair are required for an accurate resolution
      of the identity in the computation of the three- and four-electron integrals that
      arise in explicitly correlated methods.

PMID- 21861557
TI  - Time scale separation leads to position-dependent diffusion along a slow
      coordinate.
AB  - When there is a separation of time scales, an effective description of the
      dynamics of the slow variables can be obtained by adiabatic elimination of fast
      ones. For example, for anisotropic Langevin dynamics in two dimensions, the
      conventional procedure leads to a Langevin equation for the slow coordinate that
      involves the potential of the mean force. The friction constant along this
      coordinate remains unchanged. Here, we show that a more accurate, but still
      Markovian, description of the slow dynamics can be obtained by using position
      dependent friction that is related to the time integral of the autocorrelation
      function of the difference between the actual force and the mean force by a
      Kirkwood-like formula. The result is generalized to many dimensions, where the
      slow or reaction coordinate is an arbitrary function of the Cartesian
      coordinates. When the fast variables are effectively one-dimensional, the
      additional friction along the slow coordinate can be expressed in closed form for
      an arbitrary potential. For a cylindrically symmetric channel of varying cross
      section with winding centerline, our analytical expression immediately yields the
      multidimensional version of the Zwanzig-Bradley formula for the position
      dependent diffusion coefficient.

PMID- 21861558
TI  - The performance and relationship among range-separated schemes for density
      functional theory.
AB  - The performance and relationship among different range-separated (RS) hybrid
      functional schemes are examined using the Coulomb-attenuating method (CAM) with
      different values for the fractions of exact Hartree-Fock (HF) exchange (alpha),
      long-range HF (beta), and a range-separation parameter (MU), where the cases of
      alpha + beta = 1 and alpha + beta = 0 were designated as CA and CA0,
      respectively. Attenuated PBE exchange-correlation functionals with alpha = 0.20
      and MU = 0.20 (CA-PBE) and alpha = 0.25 and MU = 0.11 (CA0-PBE) are closely
      related to the LRC-omegaPBEh and HSE functionals, respectively. Time-dependent
      density functional theory calculations were carried out for a number of classes
      of molecules with varying degrees of charge-transfer (CT) character to provide an
      assessment of the accuracy of excitation energies from the CA functionals and a
      number of other functionals with different exchange hole models. Functionals that
      provided reasonable estimates for local and short-range CT transitions were found
      to give large errors for long-range CT excitations. In contrast, functionals that
      afforded accurate long-range CT excitation energies significantly overestimated
      energies for short-range CT and local transitions. The effects of exchange hole
      models and parameters developed for RS functionals for CT excitations were
      analyzed in detail. The comparative analysis across compound classes provides a
      useful benchmark for CT excitations.

PMID- 21861559
TI  - Accurate non-Born-Oppenheimer calculations of the complete pure vibrational
      spectrum of D2 with including relativistic corrections.
AB  - In this work we report very accurate variational calculations of the complete
      pure vibrational spectrum of the D(2) molecule performed within the framework
      where the Born-Oppenheimer (BO) approximation is not assumed. After the
      elimination of the center-of-mass motion, D(2) becomes a three-particle problem
      in this framework. As the considered states correspond to the zero total angular
      momentum, their wave functions are expanded in terms of all-particle, one-center,
      spherically symmetric explicitly correlated Gaussian functions multiplied by even
      non-negative powers of the internuclear distance. The nonrelativistic energies of
      the states obtained in the non-BO calculations are corrected for the relativistic
      effects of the order of alpha(2) (where alpha = 1/c is the fine structure
      constant) calculated as expectation values of the operators representing these
      effects.

PMID- 21861560
TI  - Electron pair density in the lowest 1Sigma(u)(+) and 1Sigma(g)(+) states of H2.
AB  - We demonstrate and advocate the use of observable quantities derived from the two
      electron reduced density matrix - pair densities, conditional densities, and
      exchange-correlation holes--as signatures of the type of electron correlation in
      a chemical bond. The prototype cases of the lowest (1)Sigma(u)(+) and
      (1)Sigma(g)(+) states of H(2), which exhibit large variation in types of bonding,
      ranging from strongly ionic to covalent, are discussed. Both the excited
      (1)Sigma(g)(+) and (1)Sigma(u)(+) states have been interpreted as essentially
      consisting of (natural) orbital configurations with an inner electron in a
      contracted 1ssigma(g) orbital and an outer electron in a diffuse (united atom
      type, Rydberg) orbital. We show that nevertheless totally different correlation
      behavior is encountered in various states when comparing them at a common
      internuclear distance. Also when following one state along the internuclear
      distance coordinate, strong variation in correlation behavior is observed, as
      expected. Switches between ionic to covalent character of a state occur till very
      large distances (40 bohrs for states approaching the 1s3[script-l] asymptotic
      limit, and 282 bohrs for states approaching the 1s4[script-l] limit).

PMID- 21861561
TI  - Ordinary differential equation for local accumulation time.
AB  - Cell differentiation in a developing tissue is controlled by the concentration
      fields of signaling molecules called morphogens. Formation of these concentration
      fields can be described by the reaction-diffusion mechanism in which locally
      produced molecules diffuse through the patterned tissue and are degraded. The
      formation kinetics at a given point of the patterned tissue can be characterized
      by the local accumulation time, defined in terms of the local relaxation
      function. Here, we show that this time satisfies an ordinary differential
      equation. Using this equation one can straightforwardly determine the local
      accumulation time, i.e., without preliminary calculation of the relaxation
      function by solving the partial differential equation, as was done in previous
      studies. We derive this ordinary differential equation together with the
      accompanying boundary conditions and demonstrate that the earlier obtained
      results for the local accumulation time can be recovered by solving this
      equation.

PMID- 21861562
TI  - CCSD-PCM: improving upon the reference reaction field approximation at no cost.
AB  - The combination of the coupled cluster (CC) method with the polarizable continuum
      model (PCM) of solvation requires a much larger computational effort than gas
      phase CC calculations, since the PCM contribution depends nonlinearly on the CC
      reduced density: perturbation theory energy and density (PTED) scheme. An
      approximation can be introduced that neglects the "correlation" PCM contribution
      and only considers the "reference" PCM contribution to the free energy: PTE
      scheme. The PTE scheme is a computationally efficient strategy, since the cost is
      comparable to gas phase CC, but the difference in the free energy with respect to
      the PTED scheme can be significant. In this work, two intermediate approximations
      are presented, PTE(S) and PTES (where S stands for singles), which retain the
      computational efficiency of the PTE scheme while reducing the energy gap with the
      PTED scheme. PTE(S) only introduces an energy correction to the PTE free energy,
      while PTES introduces explicit PCM terms in the iterative solution of the CC
      equations. PTE(S) improves the PTE free energy, although such correction is
      small. PTES recovers 50%-80% of the PTE-PTED difference and represents a
      promising approach to perform calculations in solution of CC quality at a cost
      comparable to gas phase CC. The expressions for the CC-PTE(S) and -PTES wave
      functions, free energy, and free energy analytical gradients are presented, and
      the methods are tested with numerical examples.

PMID- 21861563
TI  - Structure determination of the nonlinear hydrocarbon chains C9H3 and C11H3 by
      deuterium labeling.
AB  - A systematic deuterium labeling experiment is presented that aims at an
      unambiguous determination of the geometrical ground state structure of the
      C(9)H(3) and C(11)H(3) hydrocarbon chains. Cavity ring-down spectroscopy and
      special plasma expansions constituting C/H, C/D, and C/H/D are used to record
      optical transitions of both species and their (partially) deuterated equivalents
      in the 19,000 cm(-1) region. The number of observed bands, the quantitative
      determination of isotopic shifts, and supporting calculations show that the
      observed C(9)H(3) and C(11)H(3) spectra originate from HC(4)(CH)C(4)H and
      HC(4)[C(C(2)H)]C(4)H species with C(2v) symmetry. This result illustrates the
      potential of deuterium labeling as a useful approach to characterize the
      molecular structure of nonlinear hydrocarbon chains.

PMID- 21861564
TI  - Explicitly correlated treatment of H2NSi and H2SiN radicals: electronic structure
      calculations and rovibrational spectra.
AB  - Various ab initio methods are used to compute the six dimensional potential
      energy surfaces (6D-PESs) of the ground states of the H(2)NSi and H(2)SiN
      radicals. They include standard coupled cluster (RCCSD(T)) techniques and the
      newly developed explicitly correlated RCCSD(T)-F12 methods. For H(2)NSi, the
      explicitly correlated techniques are viewed to provide data as accurate as the
      standard coupled cluster techniques, whereas small differences are noticed for
      H(2)SiN. These PESs are found to be very flat along the out-of-plane and some in
      plane bending coordinates. Then, the analytic representations of these PESs are
      used to solve the nuclear motions by standard perturbation theory and variational
      calculations. For both isomers, a set of accurate spectroscopic parameters and
      the vibrational spectrum up to 4000 cm(-1) are predicted. In particular, the
      analysis of our results shows the occurrence of anharmonic resonances for H(2)SiN
      even at low energies.

PMID- 21861566
TI  - Ozone: unresolved discrepancies for dipole oscillator strength distributions,
      dipole sums, and van der Waals coefficients.
AB  - Dipole oscillator strength distributions (DOSDs) for ozone are constructed from
      experimental photoabsorption cross-sections combined with constraints provided by
      the Kuhn-Reiche-Thomas sum rule, the high-energy behavior of the dipole
      oscillator-strength density, and molar refractivity data. A lack of
      photoabsorption data in the intermediate energy region from 24 to 524 eV
      necessitates the use of a mixture rule in that region. For this purpose, a DOSD
      for O(2) is constructed first. The dipole properties for O(2) are essentially the
      same as those obtained in earlier work even though most of the input data is from
      more recent experiments. A discrepancy is found between the refractivity data and
      photoabsorption data in the 10-20.6 eV range for ozone. A reliable ozone DOSD of
      the sort obtained for many other species remains out of reach. However, it is
      suggested that the true dipole properties of ozone lie between those predicted by
      two distributions that we present.

PMID- 21861565
TI  - High-level ab initio potential energy surfaces and vibrational energies of H2CS.
AB  - Six-dimensional (6D) potential energy surfaces (PESs) of H(2)CS have been
      generated ab initio using the recently proposed explicitly correlated (F12)
      singles and doubles coupled cluster method including a perturbational estimate of
      connected triple excitations, CCSD(T)-F12b [T. B. Adler, G. Knizia, and H.-J.
      Werner, J. Chem. Phys. 127, 221106 (2007)] in conjunction with F12-optimized
      correlation consistent basis sets. Core-electron correlation, high-order
      correlation, scalar relativistic, and diagonal Born-Oppenheimer terms were
      included as additive high-level (HL) corrections. The resulting 6D PESs were
      represented by analytical functions which were used in variational calculations
      of the vibrational term values below 5000 cm(-1). The best PESs obtained with and
      without the HL corrections, VQZ-F12(*HL) and VQZ-F12*, reproduce the fundamental
      vibrational wavenumbers with mean absolute deviations of 1.13 and 1.22 cm(-1),
      respectively. A detailed analysis of the effects of the HL corrections shows how
      the VQZ-F12 results benefit from error cancellation. The present purely ab initio
      PESs will be useful as starting points for empirical refinements towards an
      accurate "spectroscopic" PES of H(2)CS.

PMID- 21861567
TI  - Prediction and characterization of HCCH...AuX (X = OH, F, Cl, Br, CH3, CCH, CN,
      and NC) complexes: a pi Au-bond.
AB  - In this article, we performed quantum chemical calculations to study the pi Au
      bond in the HCCH...AuX (X = OH, F, Cl, Br, CH(3), CCH, CN, and NC) system. For
      comparison, we also investigated the HCCH...Au(+) and H(2)CCH(2)...AuF complexes.
      The equilibrium geometries and infrared spectra at the MP2 level were reported.
      The interaction energies were calculated at the MP2 and coupled-cluster single
      double triple levels. The natural bond orbital results support the Dewar-Chatt
      Duncanson model. Moreover, we focused on the influence of X atom on the
      geometries, interaction energies, and orbital interactions as well as the
      comparison between HCCH...AuF and H(2)CCH(2)...AuF complexes. Although the pi Au
      bond in these complexes is electrostatic in nature, the weight of covalent nature
      is also important.

PMID- 21861568
TI  - Methanol nucleation in a supersonic nozzle.
AB  - We determined the partial pressures p(Jmax), temperatures T(Jmax), monomer
      supersaturations S(Jmax), and characteristic times Deltat(Jmax ) corresponding to
      the maximum nucleation rates of methanol in a supersonic nozzle. We found that
      T(Jmax) increased from 202.2 K to 223.7 K as p(Jmax) increased from 67.1 to 413.2
      Pa, while the maximum nucleation rate J(max) changed by less than a factor of 4
      over the measurement range. Our nucleation rates appear reasonably consistent
      with measurements in other devices and are within one order of magnitude of the
      nucleation rates predicted by classical nucleation theory.

PMID- 21861569
TI  - Cs atoms on helium nanodroplets and the immersion of Cs+ into the nanodroplet.
AB  - We report the non-desorption of cesium (Cs) atoms on the surface of helium
      nanodroplets (He(N)) in their 6(2)P(1/2) ((2)Pi(1/2)) state upon photo-excitation
      as well as the immersion of Cs(+) into the He(N) upon photo-ionization via the
      6(2)P(1/2) ((2)Pi(1/2)) state. Cesium atoms on the surface of helium nanodroplets
      are excited with a laser to the 6(2)P states. We compare laser-induced
      fluorescence (LIF) spectra with a desorption-sensitive method (Langmuir-Taylor
      detection) for different excitation energies. Dispersed fluorescence spectra show
      a broadening of the emission spectrum only when Cs-He(N) is excited with photon
      energies close to the atomic D(1)-line, which implies an attractive character of
      the excited state system (Cs*-He(N)) potential energy curve. The experimental
      data are compared with a calculation of the potential energy curves of the Cs
      atom as a function of its distance R from the center of the He(N) in a pseudo
      diatomic model. Calculated Franck-Condon factors for emission from the 6(2)P(1/2)
      ((2)Pi(1/2)) to the 6(2)S(1/2) ((2)Sigma(1/2)) state help to explain the
      experimental data. The stability of the Cs*-He(N) system allows to form Cs(+)
      snowballs in the He(N), where we use the non-desorbing 6(2)P(1/2) ((2)Pi(1/2))
      state as a springboard for ionization in a two-step ionization scheme. Subsequent
      immersion of positively charged Cs ions is observed in time-of-flight mass
      spectra, where masses up to several thousand amu were monitored. Only ionization
      via the 6(2)P(1/2) ((2)Pi(1/2)) state gives rise to a very high yield of immersed
      Cs(+) in contrast to an ionization scheme via the 6(2)P(3/2) ((2)Pi(3/2)) state.
      When resonant two-photon ionization is applied to cesium dimers on He droplets,
      Cs(2) (+)-He(N) aggregates are observed in time-of-flight mass spectra.

PMID- 21861570
TI  - Order parameters for the multistep crystallization of clathrate hydrates.
AB  - Recent reports indicate that the crystallization of clathrate hydrates occurs in
      multiple steps that involve amorphous intermediates and metastable clathrate
      crystals. The elucidation of the reaction coordinate for clathrate
      crystallization requires the use of order parameters able to identify the
      reactants, products, and intermediates in the crystallization pathway.
      Nevertheless, existing order parameters cannot distinguish between amorphous and
      crystalline clathrates or between different clathrate crystals. In this work, we
      present the first set of order parameters that discern between the sI and sII
      clathrate crystals, the amorphous clathrates, the blob of solvent-separated
      guests and the liquid solution. These order parameters can be used to monitor the
      advance of the crystallization and for the efficient implementation of methods to
      sample the rare clathrate nucleation events in molecular simulations. We
      illustrate the use of these order parameters in the analysis of the growth and
      the dissolution of clathrate crystals and the spontaneous nucleation and growth
      of clathrates under conditions of high supercooling.

PMID- 21861571
TI  - Extracting 2D IR frequency-frequency correlation functions from two component
      systems.
AB  - The center line slope (CLS) method is often used to extract the frequency
      frequency correlation function (FFCF) from 2D IR spectra to delineate dynamics
      and to identify homogeneous and inhomogeneous contributions to the absorption
      line shape of a system. While the CLS method is extremely efficient, quite
      accurate, and immune to many experimental artifacts, it has only been developed
      and properly applied to systems that have a single vibrational band, or to
      systems of two species that have spectrally resolved absorption bands. In many
      cases, the constituent spectra of multiple component systems overlap and cannot
      be distinguished from each other. This situation creates ambiguity when analyzing
      2D IR spectra because dynamics for different species cannot be separated. Here a
      mathematical formulation is presented that extends the CLS method for a system
      consisting of two components (chemically distinct uncoupled oscillators). In a
      single component system, the CLS corresponds to the time-dependent portion of the
      normalized FFCF. This is not the case for a two component system, as a much more
      complicated expression arises. The CLS method yields a series of peak locations
      originating from slices taken through the 2D spectra. The slope through these
      peak locations yields the CLS value for the 2D spectra at a given T(w). We derive
      analytically that for two component systems, the peak location of the system can
      be decomposed into a weighted combination of the peak locations of the
      constituent spectra. The weighting depends upon the fractional contribution of
      each species at each wavelength and also on the vibrational lifetimes of both
      components. It is found that an unknown FFCF for one species can be determined as
      long as the peak locations (referred to as center line data) of one of the
      components are known, as well as the vibrational lifetimes, absorption spectra,
      and other spectral information for both components. This situation can arise when
      a second species is introduced into a well characterized single species system.
      An example is a system in which water exists in bulk form and also as water
      interacting with an interface. An algorithm is presented for back-calculating the
      unknown FFCF of the second component. The accuracy of the algorithm is tested
      with a variety of model cases in which all components are initially known. The
      algorithm successfully reproduces the FFCF for the second component within a
      reasonable degree of error.

PMID- 21861572
TI  - Proton evolved local field solid-state nuclear magnetic resonance using Hadamard
      encoding: theory and application to membrane proteins.
AB  - NMR anisotropic parameters such as dipolar couplings and chemical shifts are
      central to structure and orientation determination of aligned membrane proteins
      and liquid crystals. Among the separated local field experiments, the proton
      evolved local field (PELF) scheme is particularly suitable to measure dynamically
      averaged dipolar couplings and give information on local molecular motions.
      However, the PELF experiment requires the acquisition of several 2D datasets at
      different mixing times to optimize the sensitivity for the complete range of
      dipolar couplings of the resonances in the spectrum. Here, we propose a new PELF
      experiment that takes the advantage of the Hadamard encoding (HE) to obtain
      higher sensitivity for a broad range of dipolar couplings using a single 2D
      experiment. The HE scheme is obtained by selecting the spin operators with phase
      switching of hard pulses. This approach enables one to detect four spin
      operators, simultaneously, which can be processed into two 2D spectra covering a
      broader range of dipolar couplings. The advantages of the new approach are
      illustrated for a U-(15)N NAL single crystal and the U-(15)N labeled single-pass
      membrane protein sarcolipin reconstituted in oriented lipid bicelles. The HE-PELF
      scheme can be implemented in other multidimensional experiments to speed up the
      characterization of the structure and dynamics of oriented membrane proteins and
      liquid crystalline samples.

PMID- 21861573
TI  - An enthalpy landscape view of homogeneous melting in crystals.
AB  - A detailed analysis of homogeneous melting in crystalline materials modeled by
      empirical interatomic potentials is presented using the theory of inherent
      structures. We show that the homogeneous melting of a perfect, infinite
      crystalline material can be inferred directly from the growth exponent of the
      inherent structure density-of-states distribution expressed as a function of
      formation enthalpy. Interestingly, this growth is already established by the
      presence of very few homogeneously nucleated point defects in the form of Frenkel
      pairs. This finding supports the notion that homogeneous melting is appropriately
      defined in terms of a one-phase theory and does not require detailed
      consideration of the liquid phase. We then apply this framework to the study of
      applied hydrostatic compression on homogeneous melting and show that the inherent
      structure analysis used here is able to capture the correct pressure-dependence
      for two crystalline materials, namely silicon and aluminum. The coupling between
      the melting temperature and applied pressure arises through the distribution of
      formation volumes for the various inherent structures.

PMID- 21861574
TI  - X-Ray absorption spectroscopy investigation of 1-alkyl-3-methylimidazolium
      bromide salts.
AB  - X-ray absorption spectroscopy (XAS) has been used to unveil the bromide ion local
      coordination structure in 1-alkyl-3-methylimidazolium bromide [C(n)mim]Br ionic
      liquids (ILs) with different alkyl chains. The XAS spectrum of 1-ethyl-3
      methylimidazolium bromide has been found to be different from those of the other
      members of the series, from the butyl to the decyl derivatives, that have all
      identical XAS spectra. This result indicates that starting from 1-buthyl-3
      methylimidazolium bromide the local molecular arrangement around the bromide
      anion is the same independently from the length of the alkyl chain, and that the
      imidazolium head groups in the liquid ILs with long alkyl chains assume locally
      the same orientation as in the [C(4)mim]Br crystal. With this study we show that
      the XAS technique is an effective direct tool for unveiling the local structural
      arrangements around selected atoms in ILs.

PMID- 21861575
TI  - The dependence of scaling law on stoichiometry for horizontally propagating
      vertical chemical fronts.
AB  - Horizontally propagating fronts in the iodate-arsenous acid reaction are
      investigated experimentally in a vertically oriented Hele-Shaw cell by varying
      the height of liquid layer for various stoichiometry. At the preset conditions, a
      stable pattern develops which can be characterized by its mixing length defined
      as the standard deviation of the front position in the direction of propagation.
      The mixing length scales with the height of the reaction vessel, and although the
      exponent significantly changes by varying the ratio of the reactants, it has a
      universal value when the reaction front is thin and simple convection arises.

PMID- 21861576
TI  - Femtosecond study of ultrafast fluorescence resonance energy transfer in a
      catanionic vesicle.
AB  - Ultrafast fluorescence resonance energy transfer (FRET) in a catanionic [sodium
      dodecyl sulfate (SDS)-dodecyltrimethyl ammonium bromide (DTAB)] vesicle is
      studied by femtosecond up-conversion. The vesicles (diameter ~400 nm for SDS-rich
      and ~250 nm for DTAB-rich vesicles) are much larger than the SDS and DTAB
      micelles (diameter ~4 nm). In both micelle and vesicles, FRET occurs in multiple
      time scales and the time scales of FRET correspond to a donor-acceptor distance
      varying between 12 and 36 A.

PMID- 21861577
TI  - Molecular dynamics simulation of cation dynamics in bis-thiourea pyridinium
      nitrate inclusion compound.
AB  - Molecular dynamics simulations have been performed on the high temperature phase
      of the bis-thiourea pyridinium nitrate inclusion compound. Three different
      potential models have been tested. In the three cases, the analysis of the centre
      of mass motion of pyridium cations indicates that they do not diffuse along the
      channels. However, only the potential including a specific hydrogen bonding
      interaction provides a description of the in-plane cation reorientation in
      reasonable agreement with the experimental results deduced from quasielastic
      neutron scattering (QENS) measurements. This model shows that the pyridinium
      cation reorients among three non-equivalent positions and gives reorientational
      correlation times comparable to those extracted from the QENS data. We conclude
      that the particular geometry of this reorientation is due to the formation of
      hydrogen bonds of different strength between the pyridinium cation of the guest
      sublattice and the host sublattice.

PMID- 21861578
TI  - Kramers problem for nonequilibrium current-induced chemical reactions.
AB  - We discuss the use of tunneling electron current to control and catalyze chemical
      reactions. Assuming the separation of time scales for electronic and nuclear
      dynamics we employ Langevin equation for a reaction coordinate. The Langevin
      equation contains nonconservative current-induced forces and gives
      nonequilibrium, effective potential energy surface for current-carrying molecular
      systems. The current-induced forces are computed via Keldysh nonequilibrium
      Green's functions. Once a nonequilibrium, current-depended potential energy
      surface is defined, the chemical reaction is modeled as an escape of a Brownian
      particle from the potential well. We demonstrate that the barrier between the
      reactant and the product states can be controlled by the bias voltage. When the
      molecule is asymmetrically coupled to the electrodes, the reaction can be
      catalyzed or stopped depending on the polarity of the tunneling current.

PMID- 21861579
TI  - The interaction of hyperthermal nitrogen with N-covered Ag(111).
AB  - A mixed beam of hyperthermal N atoms and N(2) molecules was scattered from the N
      covered Ag(111) surface held at 300 K. The angular distribution of scattered N
      atoms is very broad. In contrast, N(2) molecules exhibit a sharp angular
      distribution. Taking into account the relative mass ratio, N loses more energy at
      the surface than N(2). In terms of energy loss, the atoms approximately follow
      the binary collision model while the molecules do not. Instead, the energy curves
      of scattered N(2) are more comparable to the parallel momentum conservation model
      for near specular outgoing angles (40 degrees -65 degrees ). For both atoms and
      molecules the angle-resolved intensity and final energy curves are very similar
      to those from the bare surface. However, the N-covered surface yields non
      negligible N(2) intensity for a broad range of outgoing angles, including along
      the surface normal. This was not the case from the clean surface, where the
      measured intensity distribution was confined to the narrower angular range
      indicated above. Backscattering and direct abstraction reactions are evaluated as
      possible origins of this additional N(2) signal. Of these, an abstraction
      mechanism appears to be the most consistent with the measured data.

PMID- 21861580
TI  - Segregation of hydroxide ions to an ice surface.
AB  - Hydroxide ions that are initially buried within an ice film segregate to the ice
      film surface at elevated temperatures. This process was observed by conducting
      experiments with an ice film constructed with a bottom H(2)O layer and an upper
      D(2)O layer, with an excess of hydroxide ions trapped at the H(2)O/D(2)O
      interface as they were generated by Na hydrolysis. The transport of hydroxide
      ions from the interfacial layer to the surface was examined as a function of time
      using a low energy sputtering method. The progress of the H/D exchange reaction
      in surface water molecules was also monitored with the Cs(+) reactive ion
      scattering technique. At 90 K, only a small portion of buried hydroxide ions
      moved to the surface in the form of OD(-) species. This was due to hydroxide
      transport via proton hopping through a D(2)O layer, 3 BL thick, in the surface
      region. At 135 K, at which point water self-diffusion is active in the ice film,
      the majority of the buried hydroxide ions segregated to the surface after ~1 h.
      Both OH(-) and OD(-) species were produced at the surface, at an OH(-)/OD(-)
      population ratio >=1. Based on kinetic measurements for the transport of OH(-)
      and OD(-) species and the H/D exchange of surface water molecules, we concluded
      that the major transport channel for hydroxide ions in this regime is the
      migration of molecular hydroxide species. H/D exchange reactions also occur
      between surface hydroxide ions and water molecules. No evidence was observed for
      the occurrence of the hop-and-turn process at 135 K, although it is known as an
      important mechanism of proton transport in ice.

PMID- 21861581
TI  - Temperature and scattering contrast dependencies of thickness fluctuations in
      surfactant membranes.
AB  - Temperature and scattering contrast dependencies of thickness fluctuations have
      been investigated using neutron spin echo spectroscopy in a swollen lamellar
      phase composed of nonionic surfactant, water, and oil. In the present study, two
      contrast conditions are examined; one is the bulk contrast, which probes two
      surfactant monolayers with an oil layer as a membrane, and the other is the film
      contrast, which emphasizes an individual surfactant monolayer. The thickness
      fluctuations enhance dynamics from the bending fluctuations, and are observed in
      a similar manner in both contrast conditions. Thickness fluctuations can be
      investigated regardless of the scattering contrast, though film contrasts are
      better to be employed in terms of the data quality. The thickness fluctuation
      amplitude is constant over the measured temperature range, including in the
      vicinity of the phase boundary between the lamellar and micellar phases at low
      temperature and the boundary between the lamellar and bicontinuous phases at high
      temperature. The damping frequency of the thickness fluctuations is well scaled
      using viscosity within the membranes at low temperature, which indicates the
      thickness fluctuations are predominantly controlled by the viscosity within the
      membrane. On the other hand, in the vicinity of the phase boundary at high
      temperature, thickness fluctuations become faster without changing the mode
      amplitude.

PMID- 21861582
TI  - Thermodynamic scaling of polymer dynamics versus T-T(g) scaling.
AB  - A thermodynamic scaling law for the relaxation times of complex liquids as a
      function of temperature and volume has been proposed in the literature: tau(T,V)
      = f(TV(gamma)), where gamma is a material-dependent constant. We test this
      scaling for six materials, linear polystyrene, star polystyrene, two
      polycyanurate networks, poly(vinyl acetate), and poly(vinyl chloride), and
      compare the thermodynamic scaling to T-T(g) scaling, where tau = f(T-T(g)). The
      thermodynamic scaling law successfully reduces the data for all of the samples;
      however, polymers with similar structures but different glass transition (T(g))
      and pressure-volume-temperature (PVT) behavior, i.e., the two polycyanurates,
      cannot be superposed unless the scaling law is normalized by T(g)V(g) (gamma). On
      the other hand, the T-T(g) scaling successfully reduced data for all polymers,
      including those having similar microstructures. In addition, the T-T(g) scaling
      is easier to implement since it does not require knowledge of the PVT behavior of
      the material. The relationship between T(g)V(g) (gamma)/TV(gamma) and T-T(g)
      scaling is clarified and is found to be weakly dependent on pressure.

PMID- 21861583
TI  - Bipolaron recombination in conjugated polymers.
AB  - By using the Su-Schrieffer-Heeger model modified to include electron-electron
      interactions, the Brazovskii-Kirova symmetry breaking term and an external
      electric field, we investigate the scattering process between a negative and a
      positive bipolaron in a system composed of two coupled polymer chains. Our
      results show that the Coulomb interactions do not favor the bipolaron
      recombination. In the region of weak Coulomb interactions, the two bipolarons
      recombine into a localized excited state, while in the region of strong Coulomb
      interactions they can not recombine. Our calculations show that there are mainly
      four channels for the bipolaron recombination reaction: (1) forming a biexciton,
      (2) forming an excited negative polaron and a free hole, (3) forming an excited
      positive polaron and a free electron, (4) forming an exciton, a free electron,
      and a free hole. The yields for the four channels are also calculated.

PMID- 21861585
TI  - A stochastic surrogate Hamiltonian approach of coherent and incoherent exciton
      transport in the Fenna-Matthews-Olson complex.
AB  - The capture and transduction of energy in biological systems is clearly necessary
      for life, and nature has evolved remarkable macromolecular entities to serve
      these purposes. The Fenna-Matthews-Olson (FMO) complex serves as an intermediate
      to transfer the energy from the chlorosome to the special pairs of different
      photo systems. Recent observations have both suggested the importance of coherent
      exciton transport within the FMO and motivated an elegant and appropriate
      theoretical construct for interpreting these observations. Here we employ a
      different approach to exciton transport in a relaxing environment, one based on
      the stochastic surrogate Hamiltonian method. With it, we calculate the quantum
      trajectories through the FMO complex both for the model involving seven
      bacteriochlorophylls that has been used before, and for one involving an eighth
      bacteriochlorophyll, which has been observed in some new and very important
      structural work. We find that in both systems, efficient energy transfer to the
      ultimate receptor occurs, but that because of the placement of, and energy
      relaxation among, the different bacteriochlorophyll subunits in the FMO complex,
      the importance of coherent oscillation that was discussed extensively for the
      seven site system is far less striking for the eight site system, effectively
      because of the weak mixing between the initial site and the remainder of the
      system. We suggest that the relevant spectral densities can be determinative for
      the energy transport route and may provide a new way to enhance energy transfer
      in artificial devices.

PMID- 21861584
TI  - Vibrational spectroscopy of water in hydrated lipid multi-bilayers. I. Infrared
      spectra and ultrafast pump-probe observables.
AB  - The vibrational spectroscopy of hydration water in dilauroylphosphatidylcholine
      lipid multi-bilayers is investigated using molecular dynamics simulations and a
      mixed quantum/classical model for the OD stretch spectroscopy of dilute HDO in
      H(2)O. FTIR absorption spectra, and isotropic and anisotropic pump-probe decay
      curves have been measured experimentally as a function of the hydration level of
      the lipid multi-bilayer, and our goal is to make connection with these
      experiments. To this end, we use third-order response functions, which allow us
      to include non-Gaussian frequency fluctuations, non-Condon effects, molecular
      rotations, and a fluctuating vibrational lifetime, all of which we believe are
      important for this system. We calculate the response functions using existing
      transition frequency and dipole maps. From the experiments it appears that there
      are two distinct vibrational lifetimes corresponding to HDO molecules in
      different molecular environments. In order to obtain these lifetimes, we consider
      a simple two-population model for hydration water hydrogen bonds. Assuming a
      different lifetime for each population, we then calculate the isotropic pump
      probe decay, fitting to experiment to obtain the two lifetimes for each hydration
      level. With these lifetimes in hand, we then calculate FTIR spectra and pump
      probe anisotropy decay as a function of hydration. This approach, therefore,
      permits a consistent calculation of all observables within a unified
      computational scheme. Our theoretical results are all in qualitative agreement
      with experiment. The vibrational lifetime of lipid-associated OD groups is found
      to be systematically shorter than that of the water-associated population, and
      the lifetimes of each population increase with decreasing hydration, in agreement
      with previous analysis. Our theoretical FTIR absorption spectra successfully
      reproduce the experimentally observed red-shift with decreasing lipid hydration,
      and we confirm a previous interpretation that this shift results from the
      hydrogen bonding of water to the lipid phosphate group. From the pump-probe
      anisotropy decay, we confirm that the reorientational motions of water molecules
      slow significantly as hydration decreases, with water bound in the lipid carbonyl
      region undergoing the slowest rotations.

PMID- 21861587
TI  - Conformational flexibility and the mechanisms of allosteric transitions in
      topologically similar proteins.
AB  - Conformational flexibility plays a central role in allosteric transition of
      proteins. In this paper, we extend the analysis of our previous study [S.
      Tripathi and J. J. Portman, Proc. Natl. Acad. Sci. U.S.A. 106, 2104 (2009)] to
      investigate how relatively minor structural changes of the meta-stable states can
      significantly influence the conformational flexibility and allosteric transition
      mechanism. We use the allosteric transitions of the domains of calmodulin as an
      example system to highlight the relationship between the transition mechanism and
      the inter-residue contacts present in the meta-stable states. In particular, we
      focus on the origin of transient local unfolding (cracking), a mechanism that can
      lower free energy barriers of allosteric transitions, in terms of the inter
      residue contacts of the meta-stable states and the pattern of local strain that
      develops during the transition. We find that the magnitude of the local strain in
      the protein is not the sole factor determining whether a region will ultimately
      crack during the transition. These results emphasize that the residue
      interactions found exclusively in one of the two meta-stable states is the key in
      understanding the mechanism of allosteric conformational change.

PMID- 21861586
TI  - Diffusion-influenced ligand binding to buried sites in macromolecules and
      transmembrane channels.
AB  - We consider diffusion-influenced binding to a buried binding site that is
      connected to the surface by a narrow tunnel. Under the single assumption of an
      equilibrium distribution of ligands over the tunnel cross section, we reduce the
      calculation of the time-dependent rate coefficient to the solution of a one
      dimensional diffusion equation with appropriate boundary conditions. We obtain a
      simple analytical expression for the steady-state rate that depends on the
      potential of mean force in the tunnel and the diffusion-controlled rate of
      binding to the tunnel entrance. Potential applications of our theory include
      substrate binding to a buried active site of an enzyme and permeant ion binding
      to an internal site in a transmembrane channel.

PMID- 21861588
TI  - Occupational health of miners at altitude: adverse health effects, toxic
      exposures, pre-placement screening, acclimatization, and worker surveillance.
AB  - CONTEXT: Mining operations conducted at high altitudes provide health challenges
      for workers as well as for medical personnel. OBJECTIVE: To review the literature
      regarding adverse health effects and toxic exposures that may be associated with
      mining operations conducted at altitude and to discuss pre-placement screening,
      acclimatization issues, and on-site surveillance strategies. METHODS: We used the
      Ovid ( http://ovidsp.tx.ovid.com ) search engine to conduct a MEDLINE search for
      "coal mining" or "mining" and "altitude sickness" or "altitude" and a second
      MEDLINE search for "occupational diseases" and "altitude sickness" or "altitude."
      The search identified 97 articles of which 76 were relevant. In addition, the
      references of these 76 articles were manually reviewed for relevant articles.
      CARDIOVASCULAR EFFECTS: High altitude is associated with increased sympathetic
      tone that may result in elevated blood pressure, particularly in workers with pre
      existing hypertension. Workers with a history of coronary artery disease
      experience ischemia at lower work rates at high altitude, while those with a
      history of congestive heart failure have decreased exercise tolerance at high
      altitude as compared to healthy controls and are at higher risk of suffering an
      exacerbation of their heart failure. PULMONARY EFFECTS: High altitude is
      associated with various adverse pulmonary effects, including high-altitude
      pulmonary edema, pulmonary hypertension, subacute mountain sickness, and chronic
      mountain sickness. Mining at altitude has been reported to accelerate silicosis
      and other pneumoconioses. Miners with pre-existing pneumoconioses may experience
      an exacerbation of their condition at altitude. Persons traveling to high
      altitude have a higher incidence of Cheyne-Stokes respiration while sleeping than
      do persons native to high altitude. Obesity increases the risk of pulmonary
      hypertension, acute mountain sickness, and sleep-disordered breathing.
      NEUROLOGICAL EFFECTS: The most common adverse neurological effect of high
      altitude is acute mountain sickness, while the most severe adverse neurological
      effect is high-altitude cerebral edema. Poor sleep quality and sleep-disordered
      breathing may contribute to daytime sleepiness and impaired cognitive performance
      that could potentially result in workplace injuries, particularly in miners who
      are already at increased risk of suffering unintentional workplace injuries.
      OPHTHALMOLOGICAL EFFECTS: Adverse ophthalmological effects include increased
      exposure to ultraviolet light and xerophthalmia, which may be further exacerbated
      by occupational dust exposure. RENAL EFFECTS: High altitude is associated with a
      protective effect in patients with renal disease, although it is unknown how this
      would affect miners with a history of chronic renal disease from exposure to
      silica and other renal toxicants. HEMATOLOGICAL EFFECTS: Advanced age increases
      the risk of erythrocytosis and chronic mountain sickness in miners. Thrombotic
      and thromboembolic events are also more common at high altitude. MUSCULOSKELETAL
      EFFECTS: Miners are at increased risk for low back pain due to occupational
      factors, and the easy fatigue at altitude has been reported to further predispose
      workers to this disorder. TOXIC EXPOSURES: Diesel emissions at altitude contain
      more carbon monoxide due to increased incomplete combustion of fuel. In addition,
      a given partial pressure of carbon monoxide at altitude will result in a larger
      percentage of carboxyhemoglobin at altitude. Miners with a diagnosis of chronic
      obstructive pulmonary disease may be at higher risk for morbidity from exposure
      to diesel exhaust at altitude. CONCLUSIONS: Both mining and work at altitude have
      independently been associated with a number of adverse health effects, although
      the combined effect of mining activities and high altitude has not been
      adequately studied. Careful selection of workers, appropriate acclimatization,
      and limited on-site surveillance can help control most health risks. Further
      research is necessary to more completely understand the risks of mining at
      altitude and delineate what characteristics of potential employees put them at
      risk for altitude-related morbidity or mortality.

PMID- 21861590
TI  - Hitting the dartboard from 40,000 feet.

PMID- 21861589
TI  - Influence of chitosan coating on the liposomal surface on physicochemical
      properties and the release profile of nanocarrier systems.
AB  - Chitosan-coated nanoliposomes containing etofenprox or alpha-cypermethrin
      prepared by ultrasonic homogenization maintained a size distribution in the
      nanometre range. Nanoliposomes were constructed using different types and
      concentrations of chitosan to regulate the mean size and surface charge. As the
      chitosan concentration (0.1-0.5%, w/v) and the degree of deacetylation increased,
      surface charge also increased. The encapsulation efficiency and release profile
      were measured by gas chromatography. Encapsulation efficiency decreased slightly
      as chitosan concentration increased (0.1-0.5%, w/v). As the intrinsic surface
      charge or concentration of the coating material increased, the release period of
      the entrapped core material was extended (chitosans A and B; 0.1 and 0.3%, w/v).
      The results indicate that diverse preparation conditions could affect the
      physicochemical properties and release profile of the resulting nanocarrier
      systems.

PMID- 21861591
TI  - A potential tool for the diagnosis of ALS based on diffusion tensor imaging.
AB  - Our objective was to quantify and better understand white matter (WM) impairment
      in patients with amyotrophic lateral sclerosis (ALS) and to propose a model based
      on diffusion tensor imaging (DTI) for diagnosing patients with suspected ALS with
      upper motor neuron (UMN) signs. Twenty-six ALS patients (24 with prominent UMN
      signs and two with an isolated lower-motor neuron (LMN) syndrome) and 22 healthy
      volunteers were examined using DTI. Data analysis included voxel-based WM tract
      based spatial statistics (TBSS), volume-of-interest analysis of the TBSS results
      and stream-line tractography analysis. Converging evidence revealed WM impairment
      along the corticospinal tracts and in the mid-body of the corpus callosum. This
      was demonstrated by reduced fractional anisotropy values caused by increased
      radial diffusivity, without significant changes in axial diffusivity. There were
      no significant correlations between diffusivity indices and patients' disability
      or disease duration. A discriminant analysis model based on the tractography
      results was designed to distinguish between patients with UMN signs and controls,
      yielding 87.5% sensitivity and 85% specificity. In conclusion, DTI can detect WM
      impairment in patients with ALS in several brain regions, and might be a
      sensitive tool for the diagnosis of ALS in the early stages of the disease with
      UMN involvement.

PMID- 21861592
TI  - Supranuclear ophthalmoparesis and vacuolar degeneration of the cerebral white
      matter in amyotrophic lateral sclerosis: a clinicopathological study.
AB  - Possible clinicopathological relationship between vacuolar degeneration of
      cerebral white matter and clinical manifestation, especially of supranuclear
      ophthalmoparesis, both infrequent in amyotrophic lateral sclerosis (ALS)
      patients, was tested. Of 104 ALS sequential series, cases with vacuolar
      degeneration of the cerebral white matter were selected to yield 14 cases
      pathologically surveyed in this study. Clinical features were retrospectively
      assessed in their clinical records. Microscopic examination clarified vacuolar
      changes with fibrous gliosis, infiltration of macrophages, axonal degeneration
      with segmental dilatation and partial loss of myelin on electron microscopy. This
      histological change was extended into the cerebral white matter just under the
      cortices but sometimes accentuated as restricted areas along the pyramidal tract
      and precentral regions. In a patient with the most extensive focal lesion, these
      white matter vacuolar changes were detected with magnetic resonance imaging. The
      clinical manifestations linked to this focal vacuolar degeneration were
      disturbance of vertical ocular movements and shorter duration of the illness,
      compared with patients without vacuolar degeneration. In conclusion, histological
      demonstration of characteristic vacuolar degeneration in the white matter of ALS
      and its focal accentuation along precentral-pyramidal tracts are mutually related
      and possibly linked to clinical manifestations such as supranuclear
      ophthalmoparesis, an exceptional but possible manifestation of ALS.

PMID- 21861593
TI  - Characteristics of suicide attempts in young people undergoing treatment for
      first episode psychosis.
AB  - OBJECTIVES: Understanding the characteristics of suicide attempts in people
      undergoing treatment for first episode psychosis (FEP) may have implications for
      risk management at a service level and local suicide prevention strategies.
      Although studies have focused on identifying individual-level risk factors for
      suicide attempts in this patient group, none have yet conducted an in-depth
      profile of suicide attempts. The aim of the present study was to examine the
      characteristics of suicide attempts in young people during the initial 18 months
      of treatment for FEP. METHOD: A retrospective medical record audit study of a
      cohort of patients accepted for treatment at a specialist FEP service between
      1/12/2002 and 30/11/2005. RESULTS: Of 607 patients, 73 (12%) attempted suicide
      during treatment. Of these 73, most (72.6%) attempted suicide on one occasion.
      The majority of attempts (85.3%) occurred when patients were treated as
      outpatients and were in regular contact with the service. Suicide attempts tended
      to be impulsive (77.6%), triggered by interpersonal conflict or distress due to
      psychotic symptoms. Two thirds involved self-poisoning, usually by overdose of
      prescribed medications. All inpatient suicide attempts were by hanging or
      strangulation. Individuals infrequently sought help immediately before or after
      the attempt; if help-seeking occurred, informal sources of support were
      contacted. CONCLUSIONS: To reduce the number of suicide attempts among
      individuals treated for FEP, psychiatric services could consider: restricting the
      amount of medication prescribed per purchase; individualised suicide risk
      management plans for all newly admitted patients, including those who do not
      appear to be at risk; stringent reviews of inpatient psychiatric units for
      potential ligature points; providing information and psycho-education for
      significant others in recognition and response to suicide risk; fostering
      patients' problem solving and conflict resolution skills; and regular risk
      assessment and close monitoring of patients, particularly during the high risk
      period of 3 months after a suicide attempt.

PMID- 21861594
TI  - "Entitlement, no! Gratitude, yes!".

PMID- 21861595
TI  - Flare up of symptoms after discontinuation of sunitinib in patient with lung
      cancer.

PMID- 21861596
TI  - Suicide in breast cancer patients: an individual-centered approach provides
      insight beyond epidemiology.
AB  - BACKGROUND: Epidemiologic studies have identified increased suicide rates among
      breast cancer (BC) patients. The population-based approach, however, has
      considerable methodic shortcomings. None of the studies have been carried out in
      a prospective manner and none reported suicide rates from a country in which
      physician-assisted suicide (PAS) is legal. PATIENTS AND METHODS: All cases
      recorded by a prospective Swiss BC database during a 17-year period (1990-2006; n
      = 1165) were analyzed. Using an individual-centered approach, the cases of women
      who committed suicide are reported according to the psychological autopsy method.
      RESULTS: In six patients (0.5%; 5.1/1.000 patients), suicidal death was
      identified. In four patients, suicide was committed during late stages of
      metastatic BC. In two cases, comorbid conditions were associated with suicide.
      Three women chose PAS. CONCLUSION: The individual-centered approach is a well
      suited innovative concept to increase the knowledge regarding the relationship
      between cancer and suicide. We found a two to seven times higher suicide rate
      than those reported in epidemiologic studies. The population-based approach can
      barely elucidate the immense variety of one of the most personal decisions: the
      act of intentionally ending one's own life. These studies suffer from systematic
      failure of analysis since they did not a) consider the potential confounding role
      of comorbid medical and/or psychiatric conditions, and b) report in which disease
      stage suicide was committed, since the decisive disease-related event whether and
      when metastatic disease occurred was not recorded. Furthermore, epidemiologic
      data stems from countries in which PAS is prohibited and therefore not included
      in official statistics. This grey area of medicine accounts for a greater scope
      of underreporting than had previously been assumed.

PMID- 21861597
TI  - Does the organizational structure of health care systems influence care-seeking
      decisions? A qualitative analysis of Danish cancer patients' reflections on care
      seeking.
AB  - OBJECTIVE: The absence of a more significant improvement in cancer survival in
      countries such as the UK and Denmark may be partly rooted in delayed care-seeking
      among cancer patients. Past research on patient delay has mainly focused on
      patient characteristics (e.g. sociodemographic and psychological factors and
      symptom recognition) as causes of delayed care-seeking, while few studies have
      examined how the organizational structure of health care systems may influence
      patients' reflections on seeking care. The aim of this study was to explore this
      relationship. DESIGN: The analysis presented is based on semi-structured
      interviews with 30 cancer patients and their families. RESULTS: The article
      raises two hypotheses on the relationship between structural elements of a health
      care system and people's reflections on seeking health care: (1) Gatekeeping
      introduces an asymmetrical relationship between the patient and the GP which
      potentially results in self-restricting care-seeking, (2) Continuity in the
      doctor-patient relationship may negatively influence patient reflections on
      access to health care, as the focus shifts from the medical issues of the
      consultation to reflections on how to properly interact with the GP and the
      system in which she/he is situated. CONCLUSION: It is concluded that these
      hypotheses form a sound basis for further primary care research on how the
      organizational structure of health care systems influences patient reflections on
      access to medical care.

PMID- 21861598
TI  - The role of physician reminders in faecal occult blood testing for colorectal
      cancer screening.
AB  - BACKGROUND: Colorectal cancer screening in the form of faecal occult blood (FOB)
      testing can significantly reduce the burden of this disease and has been used as
      early as the 1970s. Effective involvement of GPs along with reminding physicians
      prior to seeing a patient may improve uptake. OBJECTIVE: This article is a
      systematic review of published literature examining the uptake of FOB testing
      after physician reminders as part of the colorectal cancer screening process.
      METHODS: Electronic databases were searched from January 1975 to October 2010.
      All studies comparing physician reminders (Rem) with controls (NRem) were
      identified. A meta-analysis was performed to obtain a summary outcome. RESULTS:
      Five comparative studies involving 25 287 patients were analyzed. There were 12
      641 patients were in the Rem and 12 646 in the NRem group. All five studies
      obtained a higher percentage uptake when physician reminders were given. However,
      in only two of the studies were the percentage uptake significantly higher. There
      was significant heterogeneity among trials (I2 = 95%). The combined increase in
      FOB test uptake was not statistically significant (random effects model: risk
      difference = 6.6%, 95% CI: -2-14.7%; z = 1.59, P = 0.112). CONCLUSION: Reminding
      physicians about those patients due for FOB testing may not improve the
      effectiveness of a colorectal cancer screening programme. Further studies are
      required and should focus on areas where there is a lower baseline uptake and
      areas with high levels of deprivation.

PMID- 21861599
TI  - General practitioners' experiences using cognitive behavioural therapy in general
      practice: a qualitative study.
AB  - OBJECTIVE: To explore GPs' experiences using cognitive behavioural therapy (CBT),
      with a focus on factors that promote or limit the use of CBT in general practice.
      DESIGN: Qualitative study using data from written evaluation reports and focus
      group interviews. Setting. Norwegian general practice. SUBJECTS: GPs who
      participated in a longitudinal CBT course in the continuous medical education
      (CME) programme for GPs in Norway, of whom 19 filled in evaluation forms and 15
      participated in focus-group interviews. MAIN OUTCOME MEASURES: Experiences with
      the use of CBT in general practice. RESULTS: GPs used CBT mainly in the treatment
      of patients with anxiety disorders and depression. Factors that promoted the use
      of CBT in general practice were structured supervision and group counselling,
      receiving feedback on individual video-recorded consultations, and experiencing
      that one mastered the therapeutic techniques. Limiting factors were that it took
      some time before one mastered the techniques, lack of eligible patients,
      constraints related to attending group supervision during office hours, and the
      lack of financial incentives to use CBT in general practice. CONCLUSION: Tailored
      training programmes in CBT for GPs may contribute to more frequent use of CBT in
      general practice. A formal recognition of CBT in the reimbursement scheme for GPs
      might counter limiting factors to an increased use of CBT in general practice.

PMID- 21861600
TI  - An automated plasma D-lactate assay with a new sample preparation method to
      prevent interference from L-lactate and L-lactate dehydrogenase.
AB  - OBJECTIVE: To establish an automated plasma D-lactate assay without interference
      from L-lactate and L-lactate dehydrogenase (L-LDH). METHODS AND MATERIALS: The D
      lactate assay was programmed as a 2-point endpoint assay on the Roche Modular P
      using the D-lactic acid kit from Biocontrol Systems, USA. In the chemical
      reaction, D-lactate was oxidized to pyruvate by NAD(+) in the presence of D
      lactate dehydrogenase. The resultant pyruvate was converted to alanine in the
      presence of alanine aminotransferase. The amount of NADH formed in the coupled
      reaction, measured by the change in the absorbance at 340 nm, was proportional to
      the concentration of D-lactate in the sample. Human serum albumin (HSA) solutions
      and plasma from pigs with experimentally-induced gut ischemia were used in this
      study. Blood samples were collected into Venosafe(r) tubes. RESULTS: The D
      lactate assay was linear up to 1.000 mmol/L in HSA solutions and plasma. The
      detection limit was 0.003 mmol/L. Within-run CVs <= 2.0% and total CVs <= 3.2%
      were obtained in the control material. Recovery was 87.1 +/- 5.2 % (Mean +/- SD).
      The L-LDH activity was completely inactivated in plasma samples by the addition
      of 20 uL of a 5 mol/L NaOH solution to 500 uL of plasma (pH 11.5). No
      interference could be detected from concentrations of bilirubin < 450 umol/L,
      haemoglobin < 0.2 mmol/L or Intralipid(r) < 2.5 g/L. CONCLUSIONS: The performance
      of the established D-lactate assay meets the requirements to be implemented into
      hospital laboratories. The sample preparation method is simple, cheap and
      requires minimal labour.

PMID- 21861601
TI  - Who is the key worker in palliative home care?
AB  - OBJECTIVE: Palliative home care involves coordination of care between the
      professionals involved. The NICE guideline on supportive and palliative care (UK)
      recommends that teams, regardless of their base, should promote continuity for
      patients. This may involve nomination of a coordinating "key worker". This study
      aimed to explore who acts as key worker and who ought to take on this role in the
      views of patients, relatives, and primary care professionals. Furthermore, it
      aimed to explore the level of agreement on this issue between study participants.
      DESIGN: Interview and questionnaire study. SETTING: Former County of Aarhus,
      Denmark (2008-2009). SUBJECTS: Ninety-six terminally ill cancer patients, their
      relatives, general practitioners (GPs), and community nurses (CNs). MAIN OUTCOME
      MEASURES: Actual key worker as valued by patients, relatives, and primary care
      professionals; ideal key worker as valued by patients and relatives. RESULTS.
      Patients, relatives, GPs, and CNs most often saw themselves as having been the
      key worker. When asked about the ideal key worker, most patients (29%; 95%CI:
      18;42) and relatives (32%; 95%CI: 22;45) pointed to the GP. Using patients' views
      as reference, we found very limited agreement with relatives (47.7%; k = 0.05),
      with GPs (30.4%; k = 0.01) and with CNs (25.0%; k = 0.04). Agreement between
      patients and relatives on the identity of the ideal key worker was of a similar
      dimension (29.6%; k = 0.11). CONCLUSION: Poor agreement between patients,
      relatives, and professionals on actual and ideal key worker emphasizes the need
      for matching expectations and clear communication about task distribution in
      palliative home care.

PMID- 21861602
TI  - Predicting future asthma morbidity in preschool inner-city children.
AB  - BACKGROUND AND AIMS: Children living in the inner city are particularly
      vulnerable to asthma. While we know much about factors that affect near-term
      outcomes in inner-city children, there is little evidence to guide clinicians on
      what to expect in the coming years, especially in preschool children. The purpose
      of our study was to determine which clinical and environmental factors are
      predictive of poor long-term asthma control in preschool inner-city children.
      MATERIALS AND METHODS: Baseline characteristics determined to be potential
      predictors of asthma severity were examined: demographics, asthma symptoms,
      medication use, healthcare utilization, early life medical history, family
      history, allergen exposure and allergic disease, and pollutant exposure.
      Bivariate and multivariate analyses were performed using logistic regression to
      examine the association of predictors of asthma severity with healthcare
      utilization at 2 years. RESULTS: Of the 150 children at baseline, the follow-up
      rate was 83% at 2 years; therefore, 124 children were included in final analyses.
      At baseline, the mean age was 4.4 years and participants were predominantly
      African-American (90%). Most of the children were atopic and 32.5% reported using
      inhaled corticosteroids. Nighttime awakening from asthma and a history of
      pneumonia were predictive of future poor control. CONCLUSION: Preschool children
      with nighttime awakening from asthma and a history of pneumonia may deserve
      closer monitoring to prevent future asthma morbidity.

PMID- 21861603
TI  - Mitogen/extracellular signal-regulated kinase kinase-5 promoter region
      polymorphisms affect the risk of sporadic colorectal cancer in a southern Chinese
      population.
AB  - Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a
      network of mitogen-activated protein kinase pathways, play a pivotal role in
      carcinogenesis. The purpose of this study was to investigate whether variants in
      the MEK5 gene promoter were involved in susceptivity of individuals to sporadic
      colorectal cancer (CRC). In the present hospital-based case-control study of 737
      patients with sporadic CRC and 703 healthy control subjects in a southern Chinese
      population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C>T and
      rs3743354T>C) were genotyped by TaqMan assay. There were significant differences
      between cases and controls in the genotype and allele distribution of the MEK5
      gene rs3743354T>C polymorphism. The rs3743354 CC genotype was associated with a
      significantly decreased risk of CRC when compared with the TT genotype (adjusted
      odds ratios [ORs]=0.43; 95% confidence interval [CI], 0.24-0.77). Compared to the
      T allele, a significant correlation was detected between the presence of the C
      allele and decreased risk of CRC (adjusted OR=0.79; 95% CI, 0.61-0.94). The
      decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT+CC)
      was found in the smoker subgroup (adjusted OR=0.63; 95% CI=0.45-0.88). Further,
      environmental factors, including smoking and drinking, interacted with rs3743354C
      variant genotypes to reduce CRC risk. Western blot analysis showed that the
      levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal
      colorectal epithelium tissues were lower in the carriers of rs3743354 CC
      genotypes than that in those with rs3743354 TT genotypes or those with rs3743354
      TC genotypes. However, no significant association was found between the
      rs7172582C>T polymorphism and risk of CRC. These data indicate that the rs3743354
      polymorphism in the MEK5 promoter may affect the risk of developing CRC.

PMID- 21861604
TI  - Binding studies of pyriproxyfen to DNA by multispectroscopic atomic force
      microscopy and molecular modeling methods.
AB  - In this work, multispectroscopic atomic force microscopy and molecular modeling
      [ONIOM 2(B3LYP/6-31++G(d,p): Universal Force Field (UFF)) level] techniques were
      used to study the interaction between Calf-Thymus-DNA (CT-DNA) and pyriproxyfen
      (PYR) insecticide. The binding constant of PYR with double-strand
      deoxyribonucleic acid (ds-DNA) was obtained by ultraviolet-visible absorbance
      spectroscopy as 2.8*10(4) at 20 degrees C. Thermodynamic parameters, that is,
      DeltaH, DeltaS degrees , and DeltaG, were -53.82 kJ mol(-1), 96.11 J mol(-1), and
      -82.46 KJ mol(-1), respectively. Thermal denaturation study of DNA with PYR
      revealed the DeltaT(m) of 3.0 and 6.0 degrees C at r(i)=0.5 and 1.0,
      respectively. The Fourier transform infrared study showed a major interaction of
      PYR with G-C and A-T base pairs and a minor perturbation of the backbone PO(2)
      group. Further, PYR induces detectable changes in the circular dichroism spectrum
      of CT-DNA. In fluorimetric studies, the dynamic enhancement constants (k(D)) and
      bimolecular enhancement constant (k(B)) were calculated, which showed that the
      fluorescence enhancement was initiated by a static process in the ground state.
      The hybrid of quantum mechanical/molecular mechanics theoretical calculations
      revealed that the interaction is base sequence dependent, and PYR interacts more
      with DNA via the AT base sequence. From the data we concluded that PYR may
      interact with ds-DNA via two modes: intercalating and outside groove binding.

PMID- 21861606
TI  - Women's and men's fertility preferences and contraceptive behaviors by HIV status
      in 10 sub-Saharan African countries.
AB  - This article draws on biomarker data from Demographic and Health Surveys (2003
      2007) in 10 sub-Saharan African countries to examine differences in fertility
      preferences and contraceptive behaviors by HIV status for women and men, taking
      into account whether or not they probably know their HIV status. The objective is
      to determine if there are common patterns in the associations between these
      variables across several countries. Women's and men's fertility preferences and
      contraceptive behaviors are relatively similar across HIV status and probable
      knowledge of that status. However, two consistent differences emerge in some of
      the countries: HIV-positive women who probably know their status are less likely
      to want more children and are more likely to be using male condoms than women who
      are HIV-negative and probably know it. A similar association is observed for men
      for condom use but not for limiting childbearing. Other factors unrelated to HIV
      status seem to be shaping women's and men's unmet demand for contraception and
      use of methods other than the condom.

PMID- 21861605
TI  - Understanding the context of HIV risk behavior among HIV-positive and HIV
      negative female sex workers and male bar clients following antiretroviral therapy
      rollout in Mombasa, Kenya.
AB  - This study explored perceptions of HIV following local introduction of
      antiretroviral therapy (ART), among 30 HIV-positive and -negative female sex
      workers (FSWs) and 10 male bar patrons in Mombasa, Kenya. Semi-structured
      interviews were analyzed qualitatively to identify determinants of sexual risk
      behaviors. ART was not perceived as a barrier to safer sex and in some cases led
      to decreased high-risk behaviors. Barriers to safer sex included economic
      pressure and sexual partnership types. Many women reported that negotiating
      condom use is more difficult in long-term partnerships. These women favored short
      term partnerships to minimize risk through consistent condom use. For women
      living with HIV, concern about maintaining health and avoiding HIV superinfection
      was a strong motivator of protective behaviors. For HIV-negative women, a
      negative HIV test was a powerful motivator. Incorporation of context- and
      serostatus-specific factors (e.g., self-protection for HIV-positive women) into
      tailored prevention counseling may support high-risk women to reduce risk
      behaviors.

PMID- 21861607
TI  - Female condom skill and attitude: results from a NIDA Clinical Trials Network
      gender-specific HIV risk reduction study.
AB  - The female condom is effective in reducing unprotected sexual acts; however, it
      remains underutilized in the United States. This study examined whether a five
      session HIV prevention intervention (Safer Sex Skills Building [SSB]), including
      presentation, discussion, and practice with female condoms, improved female
      condom skills and attitude among women in outpatient substance abuse treatment.
      Mixed-effects modeling was used to test the effect of SSB on skills and attitude
      over 3- and 6-month posttreatment among 515 randomized women. SSB was
      significantly associated with increases in skills and attitude, and the female
      condom demonstration session was primarily responsible for skills improvement.
      Attitude was a partial mediator of the intervention effect in reducing
      unprotected sex. Findings emphasize the utility of integrating female condom
      messages targeting proximal behavioral outcomes into HIV prevention. The study
      supports the use of female condom skill instruction via brief, hands-on
      exercises, as well as further research to enhance attitudinal change to reduce
      sexual risk.

PMID- 21861608
TI  - AIDS knowledge and HIV stigma among children affected by HIV/AIDS in rural China.
AB  - The current study was designed to assess the level of AIDS knowledge and its
      relationship with personal stigma toward people living with HIV/AIDS (PLWHA)
      among children living in communities of high HIV prevalence in rural China. The
      data were collected in 2009 from 118 orphanage orphans (children who had lost
      both of their parents to HIV and living in AIDS orphanages), 299 family-cared
      orphans (children who had lost one or both of their parents to HIV and living
      with surviving parents or extended families), 326 vulnerable children (children
      who were living with HIV-infected alive parents), and 276 comparison children
      (children from the same community who did not experience HIV-related illness and
      death in their family). Children were asked to answer 20 questions of AIDS
      knowledge. A 10-item stigma scale was employed to assess children's own attitude
      toward PLWHA. Both bivariate and multivariate tests were performed to answer our
      research questions. The data in the current study demonstrate a relatively low
      percent of correct AIDS knowledge (60%) among samples. The comparison children
      reported the best score of AIDS knowledge and orphanage orphans scored the
      lowest. The children with better AIDS knowledge have less personal stigma toward
      PLWHA. The findings in the current study suggest the need of appropriate
      education strategies to provide AIDS knowledge to children, particularly for HIV
      affected children living in communities of high HIV prevalence in rural China.

PMID- 21861609
TI  - Knowledge, stigma, and behavioral outcomes among antiretroviral therapy patients
      exposed to Nalamdana's radio and theater program in Tamil Nadu, India.
AB  - Arts-based programs have improved HIV-related knowledge, attitudes, and behavior
      in general and at-risk populations. With HIV transformed into a chronic
      condition, this study compares patients at consecutive stages of receiving
      antiretroviral treatment, coinciding with exposure to a radio-and-theater-based
      educational program (unexposed [N = 120], just exposed [N = 77], Exposed a month
      ago [N = 60]). Exposure was associated with significantly higher HIV-related
      knowledge (15-20%, all p < .01), lower levels of stigma (2-7% lower, all p <
      .10), and over four times the adjusted odds of asking doctors questions about HIV
      (p = .07). Higher dose of exposure was associated with lower felt stigma (28%
      reduction per message recalled), greater odds of consistent condom use (adjusted
      odds ratio [AOR]: 1.12, p = .01), doctor-patient communication (AOR: 1.20, p =
      .003), peer advice-giving (AOR: 1.18, p = .03) and HIV-related advocacy (AOR:
      2.35, p = .07). Similar partnerships between arts-based nongovernmental
      organizations and government hospitals may improve patient outcomes in HIV
      treatment settings.

PMID- 21861610
TI  - Psychological and social correlates of HIV status disclosure: the significance of
      stigma visibility.
AB  - HIV-related stigma, psychological distress, self-esteem, and social support were
      investigated in a sample comprising people who have concealed their HIV status to
      all but a selected few (limited disclosers), people who could conceal but chose
      to be open (full disclosers), and people who had visible symptoms that made
      concealing difficult (visibly stigmatized). The visibly stigmatized and full
      disclosers reported significantly more stigma experiences than limited
      disclosers, but only the visibly stigmatized reported more psychological
      distress, lower self-esteem, and less social support than limited disclosers.
      This suggests that having a visible stigma is more detrimental than having a
      concealable stigma. Differences in psychological distress and self-esteem between
      the visibly stigmatized and full disclosers were mediated by social support while
      differences between the visibly stigmatized and limited disclosers were mediated
      by both social support and stigma. These findings suggest that social support
      buffers psychological distress in people with HIV.

PMID- 21861612
TI  - Enhancing the efficiency of N-ethyl-N-nitrosourea-induced mutagenesis in the
      zebrafish.
AB  - N-Ethyl-N-nitrosourea (ENU) treatment is the standard experimental method used
      for chemical mutagenesis of many vertebrate organisms commonly used in the
      laboratory. In zebrafish and medaka, the use of a repetitive, sublethal dose of 3
      3.5 mM ENU has been shown to give the best balance between mutagenicity and
      toxicity. However, even at this concentration, a significant proportion of fish
      die during the treatment. Therefore, large numbers of fish are required to obtain
      a sufficient number of mutagenized founders at the end of the procedure.
      Additionally, it is quite common to have high levels of mortality in any
      particular dosing cycle. This may cause a mutagenesis experiment to suddenly fail
      after several weeks of work. Here we provide a very simple method for ENU
      mutagenesis of zebrafish using a subparalytic dose of clove oil as a sedative
      that drastically reduces the lethality of ENU treatment in fish. This facilitates
      ENU mutagenesis protocols considerably, facilitates higher dosing, and allows for
      sensitive strains of fish such as homozygous mutants to be mutagenized for use in
      genetic studies.

PMID- 21861613
TI  - Cancer symptom clusters: clinical and research methodology.
AB  - INTRODUCTION: Patients with cancer experience multiple symptoms that frequently
      appear in groups or clusters. We conducted a comprehensive clinical review of
      cancer symptom cluster studies to identify common symptom clusters (SC), explore
      their clinical relevance, and examine their research importance. METHODS:
      Published studies and review articles on cancer SC were obtained through a
      literature search. We identified 65 reports. These varied in assessment
      instruments, outcomes, design, population characteristics, and study methods.
      RESULTS: Two main approaches to symptom cluster identification were found:
      clinical and statistical. Clinically determined SC were based upon observations
      of symptom co-occurrence, associations, or interrelations. These included fatigue
      pain, fatigue-insomnia, fatigue-insomnia-pain, depression-fatigue, and depression
      pain. They were analyzed by multivariate analysis. They had low to moderate
      statistical correlations. Disease- or treatment-related SC were influenced by
      primary cancer site, disease stage, or antitumor treatment. SC determined by
      statistical analysis were identified by factor and cluster analysis through
      nonrandom symptom distribution. Nausea-vomiting, anxiety-depression, fatigue
      drowsiness, and pain-constipation consistently clustered by either or both of
      these statistical methods. The individual symptoms of pain, insomnia, and fatigue
      often appeared in different clusters. A consensus about standard criteria and
      methodological techniques for cluster analysis should be established.
      CONCLUSIONS: Several important cancer SC have been identified. Nausea-vomiting,
      anxiety-depression, and dyspnea-cough clusters were consistently reported. The
      techniques of symptom cluster identification remain a research tool, but one with
      considerable potential clinical importance. Further research should validate our
      analytical techniques, and expand our knowledge about SC and their clinical
      importance.

PMID- 21861614
TI  - Wearing gloves: the worst enemy of hand hygiene?

PMID- 21861616
TI  - Role of Helicobacter pylori virulence factors for iron acquisition from gastric
      epithelial cells of the host and impact on bacterial colonization.
AB  - EVALUATION OF: Tan S, Noto JM, Romero-Gallo J, Peek RM Jr, Amieva MR.
      Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the
      cell surface. PLoS Pathog. 7(5), E1002050 (2011). The effects of Helicobacter
      pylori virulence factors on gastric epithelial cells are topics open to many
      studies. Major virulence factors, cytotoxin-associated gene A (CagA) and
      vacuolating cytotoxin (VacA), predict severe infection outcomes in many
      countries. H. pylori possesses various proteins for iron transport/storage,
      however, mechanisms of iron acquisition are not fully evaluated. The study by Tan
      et al. reveals a concurrent CagA/VacA activity for micronutrient acquisition and
      host tissue colonization. The virulence factors possess new activities, involving
      VacA-induced apical mislocalization of transferrin receptors to regions of H.
      pylori attachment and effects of both factors on polarized uptake and recycling
      of transferrin. The authors used many in vitro methods and an animal model. Iron
      acquisition by CagA was proven in vitro and in vivo by strain colonization of the
      gastric mucosa in iron-depleted conditions. CagA EPIYA motifs were associated
      with increased host internalization of transferrin. Importantly, CagA and VacA
      were involved in iron acquisition and colonization without severely damaging the
      host cells, thus favoring the infection chronicity. Further studies should assess
      molecular mechanisms of H. pylori iron acquisition, comparative activities of
      contact-dependent/soluble VacA and Eastern/Western CagA on the polarized
      epithelium and long-term effects of iron deficiency by virulent versus less
      virulent H. pylori strains. An interesting topic is the association of virulent
      strains with iron deficiency anemia but also with various H. pylori-induced
      diseases, in different populations and, possibly, for other bacterial infections.
      In conclusion, H. pylori iron acquisition is multifaceted. CagA and VacA work
      concurrently to provide both iron acquisition from interstitial holotransferrin
      and enhanced bacterial colonization of host cells apically. The new activities of
      the major virulence factors of adherent H. pylori are important both to research
      and in a clinical setting.

PMID- 21861617
TI  - Antiparasitic prodrug nifurtimox: revisiting its activation mechanism.
AB  - EVALUATION OF: Hall BS, Bot C, Wilkinson SR. Nifurtimox activation by
      trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J.
      Biol. Chem. 286, 13088-13095 (2011). The prodrug nifurtimox has been one of the
      pharmacologic alternatives to treat Chagas disease and currently forms part of a
      combinational therapy to treat West African trypanosomiasis. Despite this,
      nifurtimox's mechanism of action is only partially understood and has been
      related to induction of oxidative stress in the target cell. An alternative
      mechanism involving reductive activation by a eukaryotic type I nitroreductase
      has been described. Bloodstream form Trypanosoma brucei overexpressing enzymes,
      proposed to metabolize nifurtimox, were generated and only cells with elevated
      levels of the nitroreductase displayed altered susceptibility to the drug,
      implying that it has a key role in drug action. Reduction of nifurtimox by
      trypanosomal type I nitroreductases was shown to be insensitive to oxygen and
      yielded a product characterized by liquid chromatography/mass spectrometry as an
      unsaturated open chain nitrile. This nitrile inhibited both parasite and
      mammalian cell growth at equivalent concentrations, in marked contrast to the
      parental prodrug. These studies indicated that nifurtimox selectivity against T.
      brucei could be the result of the expression of a parasite-encoded type I
      nitroreductase.

PMID- 21861618
TI  - Using infections to fight infections: paratransgenic fungi can block malaria
      transmission in mosquitoes.
AB  - EVALUATION OF: Fang W, Vega-Rodriguez J, Ghosh AK et al. Development of
      transgenic fungi that kill human malaria parasites in mosquitoes. Science
      331(6020), 1074-1077 (2011). Paratransgenesis is the genetic manipulation of
      insect endosymbiotic microorganisms such as bacteria, viruses or fungi.
      Paratransgenesis has been proposed as a potential method to control vector-borne
      diseases such as malaria. In this article, Fang and colleagues have used genetic
      manipulation to insert multiple antimalaria effector genes into the
      entomopathogenic fungus Metarhizium anisopliae. When the modified fungus was used
      to infect Anopheles mosquitoes, it expressed the antimalaria effector molecules
      in the mosquito hemolymph. When several different effector molecules were
      coexpressed, malaria levels in the mosquito salivary glands were inhibited by up
      to 98% compared with controls. Significant inhibition could be initiated by as
      little as seven fungal spores and was very rapid and long lasting. These data
      suggest that recombinant entomopathogenic fungi could be deployed as part of a
      strategy to control malaria.

PMID- 21861619
TI  - Back to the future: rising to the Semmelweis challenge in hand hygiene.
AB  - Hand hygiene is the single most important intervention for reducing healthcare
      associated infections and preventing the spread of antimicrobial resistance. This
      sentence begins most publications regarding hand hygiene in the medical
      literature. But why - as we mark 150 years since the publication of Ignaz
      Semmelweis' landmark monograph on the subject - do we continue to repeat it? One
      might be tempted to regard it as a truism. However, while tremendous progress has
      certainly been made in this field, a significant amount of work is yet to be done
      in both strengthening the evidence regarding the impact of hand hygiene and
      maximizing its implementation. Hand hygiene cannot yet be taken for granted. This
      article summarizes historical perspectives, dynamics of microbial colonization
      and efficacy of hand cleansing methods and agents, elements and impacts of
      successful hand hygiene promotion, as well as scale-up and sustainability. We
      also explore hand hygiene myths and current challenges such as monitoring,
      behavior change, patient participation and research priorities.

PMID- 21861621
TI  - Bacteriophages carrying Shiga toxin genes: genomic variations, detection and
      potential treatment of pathogenic bacteria.
AB  - Although most Escherichia coli strains occur in the mammalian intestine as
      commensals, some of them, including enterohemorrhagic E. coli (EHEC), are capable
      of causing disease in humans. The most notorious virulence factors of EHEC are
      Shiga toxins, encoded by genes located on genomes of lambdoid prophages.
      Production and release of these toxins is strongly stimulated after the induction
      of these prophages. Many antibiotics used to treat bacterial infections stimulate
      induction of Shiga toxin-converting prophages, enhancing severity of the disease
      symptoms. Hence, treatment with antibiotics is not recommended if infection with
      EHEC is confirmed or even suspected. In this light, rapid detection of EHEC is
      crucial, and understanding the mechanisms of prophage induction and phage
      development in the human intestine is important to facilitate development of
      procedures preventing or alleviating Shiga toxin-caused diseases.

PMID- 21861622
TI  - Emergence and spread of cfr-mediated multiresistance in staphylococci: an
      interdisciplinary challenge.
AB  - In staphylococci, methylation of A2503 of 23S rRNA leads to resistance against
      several classes of antibiotics (oxazolidinones, phenicols, streptogramin
      compounds, lincosamidins and pleuromutilins). The corresponding resistance gene
      cfr is located on plasmid(s) and is transferable within and between
      staphylococcal species including Staphylococcus aureus. It first emerged in
      coagulase-negative staphylococci, later in Central Europe also in S. aureus ST9
      and in methicillin-resistant S. aureus ST398, which have their main reservoir in
      pigs, and meanwhile also in nosocomial coagulase-negative staphylococci from
      Southern Europe and the USA, and furthermore in nosocomial methicillin-resistant
      S. aureus in Spain. Timely detection and targeted prevention of further
      dissemination in both human and veterinary medicine is warranted for preserving
      the activity linezolid as an important antibiotic for treatment of staphylococcal
      infections.

PMID- 21861623
TI  - Antimicrobial effects of TiO(2) and Ag(2)O nanoparticles against drug-resistant
      bacteria and leishmania parasites.
AB  - Nanotechnology is the creation of functional materials, devices and systems at
      atomic and molecular scales (1-100 nm), where properties differ significantly
      from those at a larger scale. The use of nanotechnology and nanomaterials in
      medical research is growing rapidly. Recently, nanotechnologic developments in
      microbiology have gained importance in the field of chemotherapy. Bacterial
      strains that are resistant to current antibiotics have become serious public
      health problems that raise the need to develop new bactericidal materials. Metal
      oxide nanoparticles, especially TiO(2) and Ag(2)O nanoparticles, have
      demonstrated significant antibacterial activity. Therefore, it is thought that
      this property of metal oxide nanoparticles could effectively be used as a novel
      solution strategy. In this review, we focus on the unique properties of
      nanoparticles, their mechanism of action as antibacterial agents and recent
      studies in which the effects of visible and UV-light induced TiO(2) and Ag(2)O
      nanoparticles on drug-resistant bacteria have been documented. In addition, from
      to previous results of our studies, antileishmanial effects of metal oxide
      nanoparticles are also demonstrated, indicating that metal oxide nanoparticles
      can also be effective against eukaryotic infectious agents. Conversely, despite
      their significant potential in antimicrobial applications, the toxicity of metal
      oxide nanoparticles restricts their use in humans. However, recent studies infer
      that metal oxide nanoparticles have considerable potential to be the first-choice
      for antibacterial and antiparasitic applications in the future, provided that
      researchers can bring new ideas in order to cope with their main problem of
      toxicity.

PMID- 21861624
TI  - A mass spectrometric view of the fungal wall proteome.
AB  - The walls of many fungal species consist of a polysaccharide network offering
      mechanical strength and functioning as a scaffold for covalently attached
      glycoproteins. The rapid advances in fungal genome sequencing and mass
      spectrometry have made it possible to study fungal wall proteomes in detail, both
      qualitatively and quantitatively. One of the surprising outcomes of these studies
      is the large variety of covalently attached proteins found in fungal walls.
      Another important result is that fungi can rapidly adapt the protein composition
      of their new walls to changes in environmental conditions. The wall proteome of
      the opportunistic human pathogen Candida albicans amply illustrates these
      properties. Finally, we discuss the relevance of our insights for the
      identification of new vaccine candidates.

PMID- 21861620
TI  - Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and
      therapy interrelated?
AB  - Most humans are infected with herpes simplex virus (HSV) type 1 in early
      childhood and remain latently infected throughout life. While most individuals
      have mild or no symptoms, some will develop destructive HSV keratitis. Ocular
      infection with HSV-1 and its associated sequelae account for the majority of
      corneal blindness in industrialized nations. Neuronal latency in the peripheral
      ganglia is established when transcription of the viral genome is repressed
      (silenced) except for the latency-associated transcripts and microRNAs. The
      functions of latency-associated transcripts have been investigated since 1987.
      Roles have been suggested relating to reactivation, establishment of latency,
      neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic
      shedding. Here, we review HSV-1 latent infections, reactivation, recurrent
      disease and antiviral therapies for the ocular HSV diseases.

PMID- 21861625
TI  - Recruitment of alpha7 nicotinic acetylcholine receptor to caveolin-1-enriched
      lipid rafts is required for nicotine-enhanced Escherichia coli K1 entry into
      brain endothelial cells.
AB  - AIM: We investigate how the alpha7 nicotinic acetylcholine receptor (alpha7
      nAChR), an essential regulator of inflammation, contributes to the alpha7 agonist
      nicotine-enhanced Escherichia coli K1 invasion of human brain microvascular
      endothelial cells (HBMECs) through lipid rafts/caveolae-mediated signaling.
      MATERIALS & METHODS: alpha7 nAChR-mediated signaling and bacterial invasion were
      defined by lipid raft fractionation, immunofluorescence microscopy and siRNA
      knockdown. RESULTS: Nicotine-enhanced bacterial invasion was dose-dependently
      inhibited by two raft-disrupting agents, nystatin and filipin. Significant
      accumulation of the lipid raft marker GM3 was observed in HBMEC induced by E.
      coli K1 and nicotine. The recruitment of alpha7 nAChR and related signaling
      molecules, including vimentin, and Erk1/2, to caveolin-1 enriched lipid rafts was
      increased upon treatment with E44 or E44 plus nicotine. Erk1/2 activation
      (phosphorylation), which is required for alpha7 nAChR-mediated signaling and E44
      invasion, was associated with lipid rafts and nicotine-enhanced bacterial
      infection. Furthermore, E44 invasion, E44/nicotine-induced activation of Erk1/2
      and clustering of alpha7 nAChR and caveolin-1 was specifically blocked by both
      siRNAs. CONCLUSION: alpha7 nAChR-mediated signaling through lipid rafts/caveolae
      is required for nicotine-enhanced E. coli K1 invasion of HBMEC.

PMID- 21861627
TI  - Investigating central mechanisms underlying the effects of action observation and
      imagery through transcranial magnetic stimulation.
AB  - Sport and exercise psychologists provide some interventions for clients based on
      limited direct evidence and partial understanding of the mechanisms that underpin
      their efficacy. The authors review a recent technique, transcranial magnetic
      stimulation (TMS), which offers a tested procedure for investigating cortical
      activity during observation and imagery processes. They provide a detailed
      description of the TMS protocol and highlight some of the key studies that inform
      sport and exercise psychology research. Finally, the authors offer some thoughts
      on the direct application to practice.

PMID- 21861628
TI  - The impact of real and illusory perturbations on the early trajectory adjustments
      of goal-directed movements.
AB  - Examinations of goal-directed movements reveal a process of control that operates
      to make adjustments on the basis of the expected visual afference associated with
      the limb's movement. This experiment examined the impact of perturbations to the
      perceived and actual velocity of aiming movements when each was presented alone
      or in tandem with the other. Perturbations to perceived velocity were achieved by
      translating the background over which aiming movements were performed. An aiming
      stylus that discharged air either in the direction of the movement or in the
      direction opposite the movement generated the actual velocity perturbations.
      Kinematic analyses of the aiming movements revealed that only the actual
      perturbation influenced the control of early movement trajectories. The results
      are discussed with respect to the influence that visual information has on the
      control exerted against physical perturbations. Speculations are raised regarding
      how potential for perturbations influences the strategies adopted for minimizing
      their impact.

PMID- 21861629
TI  - Pro- and antisaccades: dissociating stimulus and response influences the online
      control of saccade trajectories.
AB  - The authors examined whether the diminished online control of antisaccades is
      related to a trade-off between movement planning and control or the remapping of
      target properties to a mirror-symmetrical location (i.e., vector inversion). Pro-
      and antisaccades were examined in a standard no-delay schedule wherein target
      onset served as the movement imperative and a delay cuing schedule wherein
      responses were initiated 2,000 ms following target onset. Importantly, the delay
      cuing schedule was employed to equate pro- and antisaccade reaction times. Online
      control was evaluated by indexing the strength of trajectory amendments at
      normalized increments of movement time. Antisaccades exhibited fewer online
      corrections than prosaccades, and this result was consistent across cuing
      schedules. Thus, the diminished online control of antisaccades cannot be tied to
      a trade-off between movement planning and control. Rather, the authors propose
      that the intentional nature of dissociating stimulus and response (i.e., vector
      inversion) engenders a slow mode of cognitive control that is not optimized for
      fast oculomotor corrections.

PMID- 21861630
TI  - Psychological distress as a key component of psychosocial functioning in
      community-dwelling older people.
AB  - OBJECTIVES: To explore the key components representative of measures of
      psychosocial functioning with a focus on identifying the constituents of
      psychological distress in an Irish sample of community-dwelling older adults and
      to examine the relationship between these components and health outcomes such as
      frailty. METHOD: Cross-sectional observational study at the Technology Research
      for Independent Living (TRIL) Clinic, a comprehensive geriatric assessment
      facility in St. James's Hospital, Dublin. In this study, 579 participants were
      given eight primary assessments (Centre for Epidemiological Studies of
      Depression, Geriatric Adverse Life Events Scale, Pittsburgh Sleep Quality Index,
      De Jong-Gierveld Scale, Practitioner Assessment of Network Type, Eysenck
      Personality Inventory, Hospital Anxiety and Depression Scale, Lubben Social
      Network Scale) and a broad range of health and demographic secondary assessments.
      Principal factor analysis identified the core components relating to psychosocial
      functioning. Following this, the regression factors of these components were
      correlated with health outcomes. RESULTS: The first of three components
      identified accounted for 9.08% of the variance and related to a core internal
      component of psychological distress. The two other components related to external
      and physiological functioning, specifically social support networks and sleep.
      Spearman's Rho correlations indicated significant associations of walking speed,
      age, Berg Balance Scale and living alone with all three components. Additionally,
      the core component of psychological distress significantly correlated with the
      Fried Frailty Index, illness co-morbidity, ADL, IADL and nutrition. CONCLUSION:
      These results characterise the variation in psychosocial functioning in older
      adults and identifies psychological distress as a core facet of psychosocial
      functioning which has associations with frailty.

PMID- 21861631
TI  - A quantitative study of Michigan's criminal HIV exposure law.
AB  - The objectives of the project were (1) to determine the extent to which HIV
      positive persons living in Michigan were aware of and understood Michigan's
      criminal HIV exposure law, (2) to examine whether awareness of the law was
      associated with seropositive status disclosure to prospective sex partners, and,
      (3) to examine whether awareness of the law was associated with potential
      negative effects of the law on persons living with HIV (PLWH) including
      heightened HIV-related stigma, perceived societal hostility toward PLWH, and
      perceived need to conceal one's HIV infection. The study design was cross
      sectional. A statewide sample of 384 PLWH in Michigan completed anonymous pen and
      paper surveys in 1 of 25 data collection sessions. A majority of participants
      were aware of Michigan's HIV exposure law. Awareness of the law was not
      associated with increased seropositive status disclosure to all prospective sex
      partners, decreased HIV transmission risk behavior, or increased perceived
      responsibility for HIV transmission prevention. However, awareness of the law was
      significantly associated with disclosure to a greater proportion of sex partners
      prior to respondents' first sexual interaction with that partner. Awareness of
      the law was not associated with increased HIV-related stigma, perceived societal
      hostility toward PLWH, or decreased comfort with seropositive status disclosure.
      Evidence of an effect of Michigan's HIV exposure law on seropositive status
      disclosure was mixed. Further research is needed to examine the various forms of
      HIV exposure laws among diverse groups of persons living with or at increased
      risk of acquiring HIV.

PMID- 21861632
TI  - Post-injury delivery of rAAV2-CNTF combined with short-term pharmacotherapy is
      neuroprotective and promotes extensive axonal regeneration after optic nerve
      trauma.
AB  - Recombinant adeno-associated viral (rAAV) vectors expressing neurotrophic genes
      reduce neuronal death and promote axonal regeneration in central nervous system
      (CNS) injury models. Currently, however, use of rAAV to treat clinical
      neurotrauma is problematic because there is a delay in the onset of transgene
      expression. Using the adult rat retina and optic nerve (ON), we have tested
      whether rAAV gene therapy administered at the time of injury combined with short
      term pharmacotherapy has synergistic effects that enhance neuronal survival and
      regeneration. The ON was transected and a 1.5 cm segment of autologous peripheral
      nerve (PN) was grafted onto the cut end. At this time, bicistronic rAAV2 encoding
      ciliary neurotrophic factor (CNTF) and green fluorescent protein (rAAV2-CNTF-GFP)
      was injected into the injured eye. To provide interim support for axotomized
      retinal ganglion cells (RGCs) during vector integration and therapeutic transgene
      expression, rCNTF protein and a cyclic adenosine monophosphate (cAMP) analogue
      (CPT-cAMP) were injected intravitreally 3 and 10 days postoperatively. For
      comparison, another rAAV2-CNTF-GFP group received two intravitreal saline
      injections 3 and 10 days after the PN-ON surgery. A further PN graft group
      received only postoperative intravitreal injections of rCNTF plus CPT-cAMP. After
      4 weeks, regenerating RGCs were retrogradely labelled by applying fluorogold to
      the distal end of each PN graft. Compared to saline-injected animals, both RGC
      survival and axonal regrowth were significantly higher in the rCNTF and CPT-cAMP
      injected rAAV2-CNTF-GFP group; approximately one third of the RGC population
      survived axotomy, and 27% of these regrew an axon. These values were also higher
      than those obtained in rats that received only rCNTF plus CPT-cAMP injections.
      Therefore, we show for the first time that rAAV-mediated gene delivery at the
      time of, or just after, neurotrauma is most successful when combined with
      temporary post-injury trophic support, and is potentially a viable treatment
      strategy for patients after acute CNS injury.

PMID- 21861633
TI  - Serosorting and sexual risk behaviour according to different casual partnership
      types among MSM: the study of one-night stands and sex buddies.
AB  - Among HIV-negative men who have sex with men (MSM), any incident of unprotected
      anal intercourse (UAI) between casual partners is usually regarded as risky for
      HIV transmission. However, men are increasingly using knowledge of their casual
      partner's HIV-status to reduce HIV risk during UAI (i.e., serosorting). Since
      familiarity between casual partners may lead to higher levels of UAI and
      serosorting, we examined how often men have UAI and practice serosorting with
      three types of casual partnerships that differ in their degree of familiarity.  
      We included 240 HIV-negative men of the Amsterdam Cohort Study among MSM. We
      distinguished three types of casual partnerships: one-night stand ("met by chance
      and had sex only once"); multiple-time casual partner ("met and had sex with
      several times") and the "regular" casual partner ("sex buddy"). Serosorting was
      defined as UAI with an HIV-concordant partner. Generalised estimating equations
      analyses were used to examine the association between type of casual partnership
      and sexual risk behaviour.   Analyses revealed that men with a sex buddy were
      more likely to have UAI than men with a one-night stand (OR [95%CI] 2.39 [1.39
      4.09]). However, men with a sex buddy were also more likely to practice
      serosorting than men with a one-night stand (OR [95%CI] 5.20 [1.20-22.52]).   Men
      with a sex buddy had more UAI but also reported more serosorting than men with a
      one-night stand. As a result, the proportion of UAI without serosorting is lower
      for men with a sex buddy, and therefore men might have less UAI at risk for HIV
      with this partner type. However, the protective value of serosorting with a sex
      buddy against HIV transmission needs to be further established. At this time, we
      suggest that a distinction between the one-night stand and the sex buddy should
      be incorporated in future studies as men behave significantly different with the
      two partner types.

PMID- 21861634
TI  - Web-based parenting program to prevent adolescent alcohol misuse: rationale and
      development.
AB  - OBJECTIVES: Despite substantial evidence demonstrating the important influence
      that parents have on adolescent drinking, evidence-based preventative
      interventions that help parents to reduce the risk that their child will develop
      later alcohol use problems are lacking. Although some face-to-face family-based
      interventions for adolescent alcohol misuse have been found to be effective,
      their public health impact is limited by their labour-intensiveness, poor uptake
      and low adherence. A web-based intervention has the potential to overcome many of
      these challenges, and was recently recommended by prevention experts as one key
      way to increase participation rates in preventative interventions. This paper
      describes the development of www.parentingstrategies.net , a website providing
      parenting guidelines and a tailored web-based intervention endorsed by
      longitudinal research evidence and expert consensus. CONCLUSIONS: This website
      provides the first web-based preventative intervention for parents, and has great
      potential as a family friendly component in the spectrum of interventions that
      are critically needed to tackle the issue of adolescent alcohol misuse across the
      community.

PMID- 21861636
TI  - Antioxidant and antiproliferative activities of Helleborus odorus Waldst. & Kit,
      H. multifidus Vis. and H. hercegovinus Martinis.
AB  - This study was undertaken in order to evaluate possible antioxidative and
      antiproliferative activities of three Helleborus taxa. The dry leaves and roots
      of three Helleborus taxa were extracted with ethanol and water. A phytochemical
      evaluation of the selected extracts was performed using spectrophotometric
      methods and a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity
      assay was used for measuring the antioxidative activity of extracts. The
      antiproliferative activity of the three Helleborus taxa was studied using
      Burkitt's lymphoma B cells (BJAB) cell lines. The phytochemical evaluation showed
      that the leaves contain high levels of total phenolic and flavonoid content.
      Results from the DPPH assay indicated that the activity of the ethanol and water
      extracts of the leaves was higher than that of positive control (thymol).
      Extracts from the roots of H. odorus also displayed higher antioxidant activity
      than the positive probe, while H. mulifidus and H. hercegovinus root extracts
      were less effective. A statistically significant correlation between total
      phenolic content and antioxidative properties indicates that these compounds
      contribute to the antioxidant activity. The highest percentage of cell growth
      inhibition was observed when testing the water root extracts of H. multifidus
      (50.14%) and H. hercegovinus (49.04%). In contrast, the water leaf extract of H.
      hercegovinus exhibited the lowest inhibition of cell growth (8.59%), although it
      showed strong antioxidant activity.

PMID- 21861635
TI  - Factors affecting blast traumatic brain injury.
AB  - The overlapping pathologies and functional outcomes of blast-induced TBI (bTBI)
      and stress-related neurobehavioral disorders like post-traumatic stress disorder
      (PTSD) are significant military health issues. Soldiers are exposed to multiple
      stressors with or without suffering bTBI, making diagnosis and treatment as well
      as experimental modeling of bTBI a challenge. In this study we compared anxiety
      levels of Naive rats to ones that were exposed to each of the following
      conditions daily for 4 consecutive days: C I: transportation alone; C II:
      transportation and anesthesia; C III: transportation, anesthesia, and blast
      sounds; Injured: all three variables plus mild blast overpressure. Following
      behavioral testing we analyzed sera and select brain regions for protein markers
      and cellular changes. C I, C II, and C III animals exhibited increased anxiety,
      but serum corticosterone levels were only significantly elevated in C III and
      Injured rats. C III and Injured animals also had elevated interferon-gamma (IFN
      gamma) and interleukin-6 (IL-6) levels in the amygdala (AD) and ventral
      hippocampus (VHC). Glial fibrillary acidic protein (GFAP) levels were only
      significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured
      animals; they showed an apparent increase in ionized calcium-binding adapter
      molecule (Iba1) and GFAP immunoreactivity, as well as increased numbers of TUNEL
      positive cells in the VHC. Our findings demonstrate that experimental conditions,
      particularly the exposure to blast acoustics, can increase anxiety and trigger
      specific behavioral and molecular changes without injury. These findings should
      be taken into consideration when designing bTBI studies, to better understand the
      role of stressors in the development of post-traumatic symptoms, and to establish
      a differential diagnosis for PTSD and bTBI.

PMID- 21861637
TI  - Randomized controlled trial assessing efficacy and safety of glycine powder air
      polishing in moderate-to-deep periodontal pockets.
AB  - BACKGROUND: Supragingivally applied glycine powder air polishing (SupraGPAP) has
      been shown to remove biofilms in shallow periodontal pockets. This study assesses
      efficacy and safety of subgingivally applied glycine powder air polishing
      (SubGPAP) in moderate-to-deep periodontal pockets. METHODS: Patients with chronic
      periodontitis and intraoral Porphyromonas gingivalis (P. gingivalis) and
      Tannerella forsythia who completed initial therapy were randomly assigned to
      receive SubGPAP in periodontal pockets with probing depths of 4 to 9 mm,
      SupraGPAP in all other shallow periodontal sites, and at mucous membranes
      followed by removal of calculus using curets (full-mouth GPAP) or scaling and
      root planing followed by coronal polishing (SRP). Patients rinsed with 0.12%
      chlorhexidine gluconate after debridement, and twice daily, for 2 weeks. RESULTS:
      All 30 patients enrolled completed the baseline, day 10, and day 90 visits.
      SubGPAP resulted in significantly lower total viable bacterial counts in moderate
      to-deep pockets when compared to SRP immediately after debridement and at day 10
      (P <0.05). Total P. gingivalis counts in the oral cavity were significantly
      reduced after full-mouth GPAP compared to SRP at day 90 (P <0.05). Patients'
      comfort levels were high for both treatments. There were no adverse events
      related to full-mouth GPAP. CONCLUSIONS: The results indicate that SubGPAP is
      more efficacious in removing subgingival biofilm in moderate-to-deep periodontal
      pockets than SRP. Furthermore, full-mouth GPAP may result in a beneficial shift
      of the oral microbiota and appears to be well tolerated.

PMID- 21861638
TI  - Association between volatile sulfur compounds and periodontal disease progression
      in elderly non-smokers.
AB  - BACKGROUND: Periodontal pathogenic microorganisms produce volatile sulfur
      compounds (VSCs), such as hydrogen sulfide, methyl mercaptan, and dimethyl
      sulfide. VSCs are toxic to periodontal tissue. Therefore, there is a relationship
      between periodontitis and the VSC level of mouth air. However, the association
      between VSC and periodontal disease progression has not been investigated in a
      longitudinal study. The purpose of this study is to evaluate the association
      between VSCs in mouth air and periodontal disease progression among elderly
      dentulous non-smokers. METHODS: Two hundred forty-one dentulous non-smokers (103
      males and 138 females; all 70 years old) had their VSC levels examined with a
      portable sulfide monitor, and their periodontal status was assessed. Periodontal
      examinations were performed at baseline and once a year for 3 years to
      investigate the clinical attachment levels of all teeth. Participants were
      classified by membership in tertile groups (lowest, middle, and highest)
      according to the value of baseline VSC measurements. RESULTS: In negative
      binomial regression analysis, the number of teeth with periodontal disease
      progression for participants in the highest tertile of VSC measurement was
      greater (incidence rate ratio of 1.33, P = 0.011) than for the reference group
      (lowest tertile of VSC measurement) after simultaneously adjusting for sex,
      number of remaining teeth, and maximum clinical attachment level. CONCLUSIONS:
      VSC measurements were significantly associated with periodontal disease
      progression in a non-smoking dentulous elderly population. This suggests that VSC
      measurements are useful for the diagnosis of periodontal disease progression.

PMID- 21861639
TI  - Extraction socket preservation graft before implant placement with calcium
      sulfate hemihydrate and platelet-rich plasma: a clinical and histomorphometric
      study in humans.
AB  - BACKGROUND: The aim of this investigation is to evaluate clinical and histologic
      outcome of using medical-grade calcium sulfate hemihydrate (MGCSH) mixed with
      platelet-rich plasma (PRP) for extraction socket preservation graft before
      implant placement. METHODS: This study is a single-site, randomized and
      controlled investigation. Sixteen patients with a non-restorable tooth requiring
      extraction followed by implant placement were enrolled in this study. After
      extraction of a tooth, eight selected patients randomly received MGCSH mixed with
      PRP in the extraction sockets (test group), and eight selected patients randomly
      received collagen resorbable plug dressing material (control group). At the time
      of extraction and 3 months later (at implant placement surgery), vertical and
      horizontal socket dimensions were measured. Bone core samples were retrieved from
      the center of the healed socket before implant placement for histomorphometric
      analysis. RESULTS: There was a statistically significant difference between the
      two groups based on histomorphometric analysis (P <0.05). New vital bone
      percentage regenerated after 3 months of healing was 66.5% +/- 10.4% in sockets
      grafted with MGCSH mixed with PRP compared to 38.3% +/- 9.3% collagen resorbable
      plug. There was no statistically significant difference in the amount of vertical
      and horizontal bone resorption (P >0.05) between groups. In all cases but two in
      the control group, implants were placed with primary stability. CONCLUSION: MGCSH
      mixed with PRP showed greater vital bone volume at 3 months with rapid
      enhancement of bone healing compared to PRP-free collagen resorbable graft.

PMID- 21861640
TI  - Number of teeth is related to atherosclerotic plaque in the carotid arteries in
      an elderly population.
AB  - BACKGROUND: Periodontal disease has been associated with cardiovascular disorders
      with an atherosclerotic background, and number of teeth (NT) has been suggested
      as a possible risk indicator for cardiovascular disease. The objective of this
      study is to investigate whether NT was related to the intima-media thickness
      (IMT) and to atherosclerotic plaque in carotid arteries in an elderly population.
      METHODS: In a population-based study including 1,016 participants aged 70 years,
      the NT was self-reported by 947 of the participants. Carotid artery IMT was
      evaluated by ultrasound. The occurrence of plaque was also measured. Logistic
      regression was used to analyze the associations between NT and the number of
      carotid arteries with plaque. RESULTS: A significant inverse relationship was
      found between the NT and the number of carotid arteries with plaque after
      adjustment for age, sex, smoking, body mass index, waist/hip ratio, blood
      glucose, triglycerides, cholesterol, C-reactive protein, leukocyte count, blood
      pressure, and Framingham risk score, with odds ratio of 0.89, 95% confidence
      interval of 0.82 to 0.98, and P = 0.016. The relationship was fairly linear,
      suggesting a dose-response relationship. When NT was divided into quintiles using
      the first one as referent, the relationship persisted for all quintiles except
      for the second one. However, no relationship to IMT was seen. CONCLUSION: The
      present study further emphasizes that tooth loss could be an easily obtained risk
      indicator for atherosclerosis.

PMID- 21861641
TI  - An evaluation of bioactive glass in the treatment of periodontal defects: a meta
      analysis of randomized controlled clinical trials.
AB  - BACKGROUND: The regenerative surgical treatment of intrabony defects caused by
      periodontal disease has been examined in several systematic reviews and meta
      analyses. The use of bioactive glass (BG) as a graft material to treat intrabony
      defects has been reported, but all data have not been synthesized and compiled.
      Our objective was to systematically review the literature on the use of BG for
      the treatment of intrabony defects and to perform a meta-analysis of its
      efficacy. METHODS: A search of PubMed, EMBASE, and Cochrane Database of
      Systematic Reviews, as well as a manual search of recently published
      periodontology journals, were conducted to identify randomized controlled trials
      of the use of BG in the treatment of intrabony and furcation defects. Criteria
      included publication in English, follow-up duration of >=6 months, baseline and
      follow-up measures of probing depth (PD) and clinical attachment levels (CAL)
      with 95% confidence intervals (CIs), and an appropriate control arm. Twenty-five
      citations were identified, 15 of which were included in the final analysis. Data,
      including study methods and results, as well as CONSORT (Consolidated Standards
      of Reporting Trials) criteria, were extracted from eligible studies and cross
      checked by at least two reviewers. RESULTS: Meta-analyses of eligible studies
      were performed to ascertain summary effects for changes in PD and CAL among
      experimental and control groups, using the mean change plus standard deviation
      for each study. Pooled analyses showed that BG was superior to control for both
      measures: the mean (95% CIs) difference from baseline to follow-up between BG and
      controls was 0.52 mm (0.27, 0.78, P <0.0001) in reduction for PD and 0.60 mm
      (0.18, 1.01, P = 0.005) in gain for CAL. Analyses of CAL revealed heterogeneity
      across studies (I(2) = 60.5%), although studies reporting PD measures were
      homogeneous (I(2) = 0.00%). CAL heterogeneity appeared secondary to active
      controls versus open flap debridement (OFD) alone and to defect-type modifying BG
      treatment success. Per subgroup analyses, the benefit of BG over control
      treatment was highly significant only in studies comparing BG to OFD (P <0.0001),
      with mean difference change in CAL being 1.18 mm (95% CI = 0.74, 1.62 mm) between
      the BG and OFD group. CONCLUSION: Treatment of intrabony defects with BG imparts
      a significant improvement in both PD and CAL compared to both active controls and
      OFD.

PMID- 21861643
TI  - Antifouling and antipredatory activity of natural products of the seaweeds
      Dictyota dichotoma and Chaetomorpha linoides.
AB  - The seaweeds Dictyota dichotoma and Chaetomorpha linoides from the southeast
      coast of India were screened for anti-microfouling activity against biofilm
      bacteria, anti-macrofouling activity against brown mussels and feeding deterrence
      activity against the sea angel Monodactylus kottelati. The surface associated
      epiphytic bacteria were also isolated from seaweeds and screened for activity
      against biofilm bacteria. The acetone extracts showed a wide spectrum activity
      against biofilm bacteria and the algal metabolite was surface concentrated and
      non-polar in nature. The seaweeds also inhibited byssus production and attachment
      in brown mussels, and deterred feeding in the sea angel. The lower epiphytic
      bacterial number on the seaweed's surface compared to the surrounding seawater
      medium indicated selective inhibition or surface mediation. The epiphytic
      bacteria, which showed activity against biofilm bacteria, might also possibly
      play a role in seaweed defence strategies. The 50% deterrence of feeding activity
      at lower concentrations was not proportionate to the 100% inhibition
      concentration, which could be attributed to the adaptability of the fishes, an
      indication that the active substances are inhibitory in nature. This was further
      substantiated with the 100% recovery of mussels in a toxicity assay and the lower
      EC(50) values than LC(50) values in the mussel bioassay. The study indicates that
      the metabolites of both seaweeds have ecological significance and could possibly
      play a multifunctional role.

PMID- 21861642
TI  - Essential oil composition of the aerial parts of fresh and air-dried Salvia
      palaestina Benth. (Lamiaceae) growing wild in Jordan.
AB  - The composition of the essential oil of fresh and air-dried Salvia palaestina
      Benth. (Lamiaceae) growing wild in Jordan has been studied using gas
      chromatography-mass spectrometry analysis. The essential oils of fresh and air
      dried S. palaestina were mainly composed of sesquiterpene hydrocarbons (52.66%
      and 65.98%, respectively). The major component detected in the oils of fresh and
      dry S. palaestina was germacrene D (21.18% and 26.02%, respectively). Air drying
      resulted in a general increase of sesquiterpene hydrocarbons and a great decrease
      in the percentage of monoterpene hydrocarbons.

PMID- 21861644
TI  - Volatile chemical composition and bioactivity of six essential oils against the
      stored food insect Sitophilus zeamais Motsch. (Coleoptera Dryophthoridae).
AB  - Essential oils (EOs) of Achillea millefolium, Myrtus communis, Rosmarinus
      officinalis, Helichrysum italicum, Foeniculum vulgare and Lavandula angustifolia
      were analysed with GC-FID and GC-MS in order to define their aromatic profiles
      and then their toxicity and repellent activity against Sitophilus zeamais Motsch.
      (Coleoptera Dryophthoridae) with specific bioassays were evaluated. Results from
      topical applications on insects showed that all EOs had variable and significant
      insecticidal activity. Mortality rate never exceeded 76%. Results of repellency
      tests are indicated for M. communis and L. angustifolia EOs, displaying high
      repellent activity to S. zeamais adults.

PMID- 21861645
TI  - Comparative chemical composition and antioxidant activity of Calamintha nepeta
      (L.) Savi subsp. glandulosa (Req.) Nyman and Calamintha grandiflora (L.) Moench
      (Labiatae).
AB  - The two studied Calamintha species showed different polyphenolic content and
      sterol composition. Calamintha grandiflora possessed twice the polyphenolic
      content of Calamintha nepeta subsp. glandulosa, while the latter contained a
      higher number of sterols. Among them, stigmast-5-en-3beta-ol was found to be the
      major constituent. The methanolic extract of C. grandiflora was more potent than
      the C. nepeta subsp. glandulosa methanolic extract in a DPPH assay, while the
      activity of the C. grandiflora EtOAc fraction was weaker than its C. nepeta
      subsp. glandulosa counterpart. Fractions of C. nepeta subsp. glandulosa showed
      higher activity using a beta-carotene bleaching test. The petrol ether fraction
      of C. grandiflora showed significant inhibition of NO production.

PMID- 21861646
TI  - Evaluation of the natural product antifoulant, zosteric acid, for preventing the
      attachment of quagga mussels--a preliminary study.
AB  - The effectiveness of zosteric acid, a natural antifoulant from the marine
      seagrass Zostera marina, in preventing the attachment of quagga mussels, a
      biofouling bivalve, was investigated. Animals were exposed to water containing
      zosteric acid ranging from 0 to 1000 ppm, and their attachment to the container
      glass walls was tracked with time. 500 ppm zosteric acid was not effective at
      detaching animals that had already attached, but was able to prevent the
      attachment of most unattached animals for two days. The anti-fouling effect
      increased with higher concentration. Low concentrations (250 ppm and below) were
      not effective at preventing attachment; however, 1000 ppm zosteric acid prevented
      attachment of mussels for the first three days of zosteric acid exposure, and
      only 20% of the mussels were attached by day 4. In contrast, animals in control
      (no zosteric acid) solutions began to attach within one day. In conclusion,
      zosteric acid is an effective natural product deterrent of attachment of a
      biofouling bivalve.

PMID- 21861647
TI  - Adsorption of Remazol Brilliant Blue R on activated carbon prepared from a pine
      cone.
AB  - In this work the activated pine cone was investigated as adsorbent to remove
      Remazol Brilliant Blue R from aqueous solution. The effects of various
      experimental parameters such as initial dye concentration, contact time,
      temperature, adsorbent dose and pH were examined. The adsorption of Remazol
      Brilliant Blue R from aqueous solution was increased with the increase in initial
      dye concentration, contact time, temperature, adsorbent dose but decreased with
      the increase in the pH. The results in this study indicated that the activated
      pine cone was an attractive candidate for removing Remazol Brilliant Blue R.

PMID- 21861648
TI  - Chemical constituents of Caryopteris tangutica.
AB  - A new compound (1), along with 18 known compounds, was isolated from Caryopteris
      tangutica. On the basis of spectroscopic methods, with special emphasis on 1D-
      and 2D-NMR techniques, the structure of the new compound was characterised as 6
      hydroxy-6-methylcyclohex-2-en-1-one (1).

PMID- 21861649
TI  - Calcium sensitization involved in dexmedetomidine-induced contraction of isolated
      rat aorta.
AB  - Dexmedetomidine, a full agonist of the alpha2B-adrenoceptor that is mainly
      involved in vascular smooth muscle contraction, is primarily used for analgesia
      and sedation in intensive care units. High-dose dexmedetomidine produces
      hypertension in children and adults. The goal of this in vitro study was to
      investigate the role of the calcium (Ca(2+)) sensitization mechanism involving
      Rho-kinase, protein kinase C (PKC), and phosphoinositide 3-kinase (PI3-K) in
      mediating contraction of isolated rat aortic smooth muscle in response to
      dexmedetomidine. The effect of dexmedetomidine on the intracellular Ca(2+) level
      ([Ca(2+)]i) and tension was measured simultaneously. Dexmedetomidine
      concentration-response curves were generated in the presence or absence of the
      following antagonists: rauwolscine, Y 27632, LY 294002, GF 109203X, and
      verapamil. Dexmedetomidine-induced phosphorylation of PKC and membrane
      translocation of Rho-kinase were detected with Western blotting. Rauwolscine, Y
      27632, GF 109203X, LY 294002, and verapamil attenuated dexmedetomidine-induced
      contraction. The slope of the [Ca(2+)]i-tension curve for dexmedetomidine was
      higher than that for KCl. Dexmedetomidine induced phosphorylation of PKC and
      membrane translocation of Rho-kinase. These results suggest that dexmedetomidine
      induced contraction involves a Ca(2+) sensitization mechanism mediated by Rho
      kinase, PKC, and PI3-K that is secondary to alpha2-adrenoceptor stimulation in
      rat aortic smooth muscle. 

PMID- 21861650
TI  - Bio-ecology of the louse, Upupicola upupae, infesting the Common Hoopoe, Upupa
      epops.
AB  - Abstract The population characteristics of the louse, Upupicola upupae (Shrank)
      (Mallophaga: Philopteridae: Ishnocera), infesting the Common Hoopae, Upupa epops
      L. (Aves: Upupiformes), were recorded during 2007-08 in District Rampur, Uttar
      Pradesh India. The pattern of frequency distribution of the louse conformed to
      the negative binomial model. The lice and its nits were reared in vitro at 35 +/-
      1 degrees  C, 75-82 % RH, on a feather diet. The data obtained was used to
      construct the life table and to determine the intrinsic rate of natural increase
      (0.035 female/day), the net reproductive rate was 3.67 female eggs/female, the
      generation time was 37 days, and the doubling time of the population was 19 days.
      The chaetotaxy of the three nymphal instars has also been noted to record their
      diagnostic characteristics. Information on egg morphology and antennal sensilla
      is also presented.

PMID- 21861651
TI  - The parasitoid, Verticia fasciventris causes morphological and behavioral changes
      in infected soldiers of the fungus-growing termite, Macrotermes carbonarius.
AB  - The larval parasitoid Verticia fasciventris Malloch (Diptera: Calliphoridae)
      develops in the head of soldiers of the fungus-growing termite Macrotermes
      carbonarius (Hagen) (Isoptera: Termitidae). Morphological and behavioral changes
      in the host were evaluated and the termite castes and stages that were
      parasitized were identified. The larval emergence process is also described and
      possible mechanisms for the parasitoid fly's entry into the host body are
      discussed based on qualitative observations. Only a single larva per host was
      found. The mature larva pupated outside the host's body by exiting between the
      abdominal cerci. Parasitized soldiers possess a short and square-shaped head
      capsule, a pair of notably short mandibles, and a pair of 18-segmented antennae.
      Although parasitized soldiers were statistically less aggressive than healthy
      soldiers (P < 0.05), they expressed varying levels of aggression. Both minor and
      major soldiers can be parasitized and based on evidence from presoldiers,
      parasitization may begin during the precursor stages of soldiers. However, the
      stage at which parasitism first occurs has not been determined.

PMID- 21861652
TI  - Effect of natural and artificial photoperiods and fluctuating temperature on age
      of first mating and mating frequency in the navel orangeworm, Amyelois
      transitella.
AB  - The effect of weak illumination during part or all of the scotophase on mating
      frequency of navel orangeworm, Amyelois transitella (Walker) (Lepidoptera:
      Pyralidae), was examined in environmental chambers under long photoperiods and
      constant warm temperature (colony conditions) or shorter photoperiods and a
      cooler thermoperiod intended to mimic spring conditions in our region. These data
      were compared to mating frequencies in sentinel females placed in the field
      during the first three weeks of May. Under colony conditions weak illumination in
      the final hour of the scotophase resulted in ~90% mating on the first day after
      eclosion; significantly greater mating compared to complete darkness throughout
      the scotophase, weak illumination throughout the scotophase, or weak illumination
      for both the first and last hour of the scotophase. In an environmental chamber
      programmed to simulate spring conditions, little mating occurred on the first
      night after eclosion and three nights were required for more than 50% of the
      females to mate. There was no difference in mating frequency with between moths
      exposed to complete darkness throughout the scotophase and those provided with
      weak illumination in the last half hour of the scotophase or throughout the
      scotophase. This delay in age of first mating was consistent with field
      observations with sentinel females at May in the central San Joaquin Valley. The
      authors conclude that, along with greater longevity and later oviposition, first
      mating occurs at a later age in spring conditions compared to summer conditions
      in this species. Planned studies of the effect of delayed mating in first and
      second flights will need to take these factors into account.

PMID- 21861653
TI  - Aerial insecticide treatments for management of Dectes stem borer, Dectes
      texanus, in soybean.
AB  - The Dectes stem borer, Dectes texanus LeConte (Coleoptera: Cerambycidae), is an
      increasingly important pest of soybean and sunflower in central North America.
      Nine large-scale field trials were conducted over a 3-year period to determine if
      Dectes stem borer could be managed with insecticide treatments. Aerial
      applications of lambda on July 6, 12 and 15 were successful in significantly
      reducing adults, but applications on July 1, 20 and 24 were less successful.
      These data suggest that for central Kansas two aerial applications may be
      required to control Dectes stem borers in soybean. Based on our experience the
      first application should be made at the peak of adult flight about July 5(th) and
      the second application 10 days later. The local treatment schedule should be
      developed to follow the local Dectes stem borer adult emergence pattern. Treated
      aerial strips 59 m (195 ft) wide were not large enough to prevent reinfestation,
      but treated half-circles (24 ha or 60 acres) were successful in reducing in
      Dectes stem borer infestation of soybean. Sweep net samples of adults were not
      successful in identifying a treatment threshold, so treatment decisions will need
      to be based on field history of infestation. Further studies are needed to
      identify better sampling methods that can be used to establish treatment
      thresholds and to refine the best timing for treatments.

PMID- 21861655
TI  - Fungal spore-feeding thrips (Thysanoptera: Phlaeothripidae: Ldolothripinae) from
      Iran with record of a fourth genus.
AB  - The genus Allothrips Hood, with one species A. bournieri Mound, is reported for
      the first time in Iran and the generic classification of Phlaeothripidae is
      discussed briefly. A key is provided to distinguish the four genera recorded in
      Iran of the spore-feeding thrips in the Idolothripinae.

PMID- 21861654
TI  - Fine structure of the sensilla and immunolocalisation of odorant binding proteins
      in the cerci of the migratory locust, Locusta migratoria.
AB  - Using light and electron microscopy (both scanning and transmission), we observed
      the presence of sensilla chaetica and hairs on the cerci of the migratory locust,
      Locusta migratoria L. (Orthoptera: Acrididae). Based on their fine structures,
      three types of sensilla chaetica were identified: long, medium, and short. Males
      presented significantly more numbers of medium and short sensilla chaetica than
      females (p<0.05). The other hairs can also be distinguished as long and short.
      Sensilla chaetica were mainly located on the distal parts of the cerci, while
      hairs were mostly found on the proximal parts. Several dendritic branches,
      enveloped by a dendritic sheath, are present in the lymph cavity of the sensilla
      chaetica. Long, medium, and short sensilla chaetica contain five, four and three
      dendrites, respectively. In contrast, no dendritic structure was observed in the
      cavity of the hairs. By immunocytochemistry experiments only odorant-binding
      protein 2 from L. migratoria (LmigOBP2) and chemosensory protein class I from the
      desert locust, Schistocerca gregaria Forsskal (SgreCSPI) strongly stained the
      outer lymph of sensilla chaetica of the cerci. The other two types of hairs were
      never labeled. The results indicate that the cerci might be involved in contact
      chemoreception processes.

PMID- 21861656
TI  - Sexual dimorphism of pupae and adults of the cocoa pod borer, Conopomorpha
      cramerella.
AB  - This paper describes the main distinguishing characteristics of female and male
      pupae and adults of cocoa pod borer, Conopomorpha cramerella (Snellen)
      (Lepidoptera: Gracillariidae). Two pairs of tubercles present on the sterna of
      segments IX and X of the female pupae are useful in differentiating female from
      male pupae. The female genital opening is located anterior to the first pair of
      tubercles and forms a plateau in which the center has a light brown longitudinal
      depression that indicates the female genital opening. The male genital opening is
      a conspicuous, brown, longitudinal slit located between the two pairs of
      tubercles. The sex of the adult moth can be determined by examining the
      ventrocaudal segments of the abdomen. The last segment of the female abdomen is
      white, compressed laterally and at the tip, and the hairy anal papillae can be
      seen. In the male, the ventrocaudal end of the abdomen is black and robust. This
      information will be useful for laboratory and field diagnosis and while working
      on sex ratios of this important pest of cocoa.

PMID- 21861657
TI  - Purification and characterization of cytoplasmic NADP+-isocitrate dehydrogenase,
      and amplification of the NADP+-IDH gene from the wing-dimorphic sand field
      cricket, Gryllus firmus.
AB  - Cytoplasmic NADP(+)-isocitrate dehydrogenase (NADP(+)-IDH) has been purified and
      characterized, and its gene sequenced in many animal, plant, and yeast species.
      However, much less information is available on this enzyme-gene in insects. As a
      first step in investigating the biochemical and molecular mechanisms by which
      NADP(+)-IDH contributes to adaptations for flight vs. reproduction in insects,
      the enzyme was purified to homogeneity in the wing-dimorphic cricket, Gryllus
      firmus, characterized, and its corresponding gene sequenced. Using a combination
      of polyethylene glycol precipitation, Cibacron-Blue affinity chromatography, and
      hydrophobic interaction chromatography the enzyme was purified 291-fold (7%
      yield; specific activity = 15.8 umol NADPH/min/mg protein). The purified enzyme
      exhibited a single band on SDS PAGE (46.3 kD), but consisted of two N-terminal
      amino acid sequences that differed in the first two amino acids. Purified enzyme
      exhibited standard Michaelis-Menten kinetics at pH 8.0 and 28 degrees  C
      (K(M(NADP+)) = 2.3 +/- 0.4 uM; K(M(Na+-Isocitrate)) = 14.7 + 1.8 uM). Subunit
      molecular mass and K(M)S were similar to published values for NADP(+)-IDHs from a
      variety of vertebrate and two insect species. PCR amplification of an internal
      sequence using genomic DNA followed by 3' and 5' RACE yielded a nucleotide
      sequence of the mature protein and translated amino-acid sequences that exhibited
      high similarity (40-50% and 70-80%, respectively) to sequences from insect and
      vertebrate NADP(+)-IDHs. Two potential ATG start codons were identified. Both
      Nterminal amino-acid sequences matched the nucleotide sequence, consistent with
      both enzyme forms being transcribed from the same gene, although these variants
      could also be encoded by different genes. Bioinformatic analyses and differential
      centrifugation indicated that the majority, if not all, of the enzyme is
      cytoplasmic. The enzyme exhibited high specific activity in fat body, head and
      gut, and a single band on native PAGE.

PMID- 21861658
TI  - Geographical distribution of the space-weaving spider, Chibchea salta, from
      northwestern Argentina: New records and bioclimatic modeling.
AB  - New records of the spider Chibchea salta Huber 2000 (Araneae, Pholcidae) from
      northwestern Argentina are provided, and the potential range of this species is
      modeled. Two presence-only methods, Maxent and Bioclim, were run using 19
      bioclimatic parameters at a resolution of 30 arc seconds. The climatic profile of
      C. salta is described, and the relative importance of the bioclimatic variables
      is explored. Temperature variables proved to be more decisive to the final range
      shape. The range predicted with Maxent is slightly larger than with Bioclim, but
      the latter appears to be more sensitive to the record set bias. Both methods
      performed well, resulting in predictive ranges consistent with the yungas
      ecoregion. These results provide an initial insight into the bioclimatic
      tolerance of C. salta, and by identifying potential areas with no records, such
      as the sierras on the Salta-Jujuy border, they also help in identifying sites for
      future sampling efforts.

PMID- 21861659
TI  - Trail marking by caterpillars of the silverspot butterfly Dione juno huascuma.
AB  - A pheromone is implicated in the trail marking behavior of caterpillars of the
      nymphalid silverspot butterfly, Dione juno huascuma (Reakirt) (Lepidoptera:
      Heliconiinae) that feed gregariously on Passiflora (Malpighiales: Passifloraceae)
      vines in Mexico. Although they mark pathways leading from one feeding site to
      another with silk, this study shows that the silk was neither adequate nor
      necessary to elicit trail following behavior. Caterpillars marked trails with a
      long-lived pheromone that was deposited when they brushed the ventral surfaces of
      the tips of their abdomens along branch pathways. The caterpillars distinguished
      between pathways deposited by different numbers of siblings and between trails of
      different ages. Caterpillars also preferentially followed the trails of
      conspecifics over those of another nymphalid, Nymphalis antiopa L., the mourning
      cloak butterfly.

PMID- 21861660
TI  - New diagnostic criteria for Alzheimer's disease.

PMID- 21861661
TI  - Role of amyloid beta1-42 and neuroimaging biomarkers in Alzheimer's disease.

PMID- 21861662
TI  - Neutrophil gelatinase-associated lipocalin: a superior biomarker for detection of
      subclinical acute kidney injury and poor prognosis.

PMID- 21861665
TI  - Novel drug metabolism indices for pharmacogenetic functional status based on
      combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes.
AB  - AIMS: We aim to demonstrate clinical relevance and utility of four novel drug
      metabolism indices derived from a combinatory (multigene) approach to CYP2C9,
      CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as
      complementary components of a liver enzyme drug metabolism system and uniquely
      benchmarks innate hepatic drug metabolism reserve or alteration through CYP450
      combinatory genotype scores. METHODS: A total of 1199 psychiatric referrals were
      genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were
      scored on each of the four indices. The data were used to create distributions
      and rankings of innate drug metabolism capacity to which individuals can be
      compared. Drug-specific indices are a combination of the drug metabolism indices
      with substrate-specific coefficients. RESULTS: The combinatory drug metabolism
      indices proved useful in positioning individuals relative to a population with
      regard to innate drug metabolism capacity prior to pharmacotherapy. Drug-specific
      indices generate pharmacogenetic guidance of immediate clinical relevance, and
      can be further modified to incorporate covariates in particular clinical cases.
      CONCLUSIONS: We believe that this combinatory approach represents an improvement
      over the current gene-by-gene reporting by providing greater scope while still
      allowing for the resolution of a single-gene index when needed. This method will
      result in novel clinical and research applications, facilitating the translation
      from pharmacogenomics to personalized medicine, particularly in psychiatry where
      many drugs are metabolized or activated by multiple CYP450 isoenzymes.

PMID- 21861666
TI  - Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with
      pharmacogenetic functional status in psychiatric patients.
AB  - AIMS: To investigate associations between novel human cytochrome P450 (CYP450)
      combinatory (multigene) and substrate-specific drug metabolism indices, and
      elements of metabolic syndrome, such as low density lipoprotein cholesterol
      (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using
      physiogenomic analysis. METHODS: CYP2C9, CYP2C19 and CYP2D6 genotypes and
      clinical data were obtained for 150 consecutive, consenting hospital admissions
      with a diagnosis of major depressive disorder and who were treated with
      psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc,
      triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug
      metabolism indices. RESULTS: We found that a greater metabolic reserve index
      score is related to lower LDLc and higher HDLc, and that a greater metabolic
      alteration index score corresponds with higher LDLc and lower HLDc values. We
      also discovered that the sertraline drug-specific indices correlated with
      cholesterol and triglyceride values. CONCLUSIONS: Overall, we demonstrated how a
      multigene approach to CYP450 genotype analysis yields more accurate and
      significant results than single-gene analyses. Ranking the individual with
      respect to the population represents a potential tool for assessing risk of
      dyslipidemia in major depressive disorder patients who are being treated with
      psychotropics. In addition, the drug-specific indices appear useful for modeling
      a variable of potential relevance to an individual's risk of drug-related
      dyslipidemia.

PMID- 21861667
TI  - Serum fatty acid profiling of colorectal cancer by gas chromatography/mass
      spectrometry.
AB  - AIMS: Several screening methods have been applied for the early diagnosis of
      colorectal cancer, but most colorectal cancer patients are not diagnosed at a
      localized stage. In order to find novel biomarkers for the diagnosis of
      colorectal cancer, profiling of the serum levels of fatty acids, which are the
      main components of fats and are important factors for human metabolism, was
      performed using the sera of colorectal cancer patients. MATERIALS & METHODS: A
      total of 42 colorectal cancer patients and eight healthy volunteers participated
      in this study. The serum levels of fatty acids, including free fatty acids and
      esterified fatty acids, were evaluated by gas chromatography/mass spectrometry.
      Then, partial least squares discriminant analysis was performed on the basis of
      the serum fatty acids detected by gas chromatography/mass spectrometry. RESULTS:
      The serum levels of the nine fatty acids exhibited distinct differences between
      the colorectal cancer patients and healthy volunteers: the levels of four fatty
      acids were higher in the colorectal cancer patients than the healthy volunteers,
      and those of the other five fatty acids were lower. These changes were also
      observed at a very early clinical stage. Furthermore, the levels of very-long
      chain fatty acids had a tendency to be increased in the sera of the colorectal
      cancer patients. CONCLUSIONS: The pathogenesis of colorectal cancer leads to
      changes in the composition of serum fatty acids including free fatty acids and
      esterified fatty acids. These results suggest that serum fatty acid profiling may
      be used as a novel diagnostic tool for early-stage colorectal cancer.

PMID- 21861668
TI  - IL28B polymorphism and genetic biomarkers of viral clearance in hepatitis C virus
      infection.
AB  - Infection with hepatitis C virus (HCV) is a major global health issue. Only a
      small proportion of patients clear the virus spontaneously and the majority
      develop chronic hepatitis C infection. Chronic hepatitis C is one of the most
      common causes of advanced liver disease in the western world and is now the
      leading indication for liver transplantation. Unfortunately, the standard
      treatment, consisting of pegylated-interferon and ribavirin, is suboptimal. Less
      than 50% of patients infected with HCV genotype 1 are cured, treatment is costly
      and is associated with significant toxicity. Therefore, there has been a need to
      identify accurate predictors of treatment outcome to facilitate treatment
      decision-making. Four independent genome-wide association studies have recently
      confirmed an association between genetic variation in the region of the IL28B
      gene and treatment outcome in HCV-1 patients. Patients who carry the good
      response variant are two- to three-fold more likely to be cured. The difference
      in the frequency of the good response variant between patients of different
      ethnic background explains much of the recognized ethnic disparity in treatment
      response rates. The IL28B variants are also associated with likelihood of
      spontaneous clearance of HCV infection. This discovery represents a significant
      advance in our ability to personalize HCV therapy, as well as suggesting novel
      avenues for research into viral pathogenesis and therapeutic development.

PMID- 21861669
TI  - Role of CSF biomarkers in the diagnosis of prodromal Alzheimer's disease.
AB  - Alzheimer's disease (AD) core biomarkers (Abeta(1-42), total tau and
      phosphorylated tau) have proven to be useful in the clinical practice to evaluate
      patients with mild cognitive impairment in order to predict progression to
      Alzheimer's disease. Multicenter studies have shown an good overall performance
      of Abeta(1-42), total tau and phosphorylated tau in the diagnosis of early AD;
      however, they also evidenced some possible weakness in terms of variability among
      centers, which generates some concern about their use in routine clinical
      practice. Therefore, the need for a joint effort of academia, companies and
      government agencies is evident. In this article we will provide the state of art
      of AD biomarkers application for the diagnosis of early AD, also describing some
      of the most promising new putative biomarkers currently studied. The final aim is
      to introduce a panel of AD biomarkers that is able to describe the preclinical
      phases of AD, as fully as possible paving the way to a routine early diagnosis in
      view of treatment by means of disease-modifying drugs.

PMID- 21861670
TI  - Biomarkers for predicting postmenopausal coronary heart disease.
AB  - Coronary heart disease (CHD) is the main cause of death in post-menopausal women
      (PMW). Beyond the 'traditional' cardiovascular risk factors of CHD, newer
      biomarkers, reflecting inflammation, endothelial function and oxidative stress,
      have received growing consideration. We systematically reviewed the literature on
      the biomarkers for predicting CHD in PMW. C-reactive protein, IL-6 and
      Lipoprotein (a) have been consistently found to be associated with CHD risk in
      PMW. However, no evidence supports the existence of a causal and independent link
      between such biomarkers and CHD in PMW. Also, the new biomarkers only marginally
      improve cardiovascular risk prediction. Upcoming studies are needed to provide
      further evidence on the validity of the new biomarkers in PMW and to understand
      their relationships with hormone therapy, opening new avenues for prevention.

PMID- 21861671
TI  - Promise of new translational safety biomarkers in drug development and challenges
      to regulatory qualification.
AB  - One promise of new translational safety biomarkers (TSBs) is their ability to
      demonstrate that toxicities in animal studies are monitorable at an early stage,
      such that human relevance of potential adverse effects of drugs can be safely and
      definitively evaluated in clinical trials. Another is that they would provide an
      earlier, more definitive and deeper insight to patient prognosis compared with
      conventional biomarkers. Recent experience with regulatory authorities indicates
      that resource demands for new TSB qualifications under the current framework are
      daunting and the rate of their expansion will be slow, particularly in light of
      mounting financial pressures on the pharmaceutical industry. Sponsors face a
      dilemma over engaging in safety biomarker qualification consortia. While it is
      clear new TSBs could be considered catalysts to drug development and that patient
      health, business and scientific benefits, described here using examples, should
      outweigh qualification costs, concerns exist that early ambiguities in biomarker
      interpretations at the introduction of such new TSBs might hinder drug
      development.

PMID- 21861672
TI  - Prostate-specific antigen testing across the spectrum of prostate cancer.
AB  - Prostate-specific antigen (PSA) is a protein produced by the prostate, and this
      protein may be elevated for several reasons, including prostatitis, benign
      prostatic hypertrophy and/or cancer. PSA is not cancer-specific, cannot be used
      as a cancer marker and it has been demonstrated that there is no level of PSA
      that is definitive for prostate cancer. The value of the PSA test varies when
      used for screening, diagnosis, prognosis or as a signal of disease recurrence.
      Misuse of the test for screening has created unnecessary anxiety and costs, and
      has led to the significant overdiagnosis and overtreatment of men. More important
      than whether or not to screen is how one acts upon the data from a single test;
      with the exception of extremely high double- or triple-digit levels of PSA, it is
      prudent only to use a single PSA determination as a baseline, with biopsy and
      cancer treatment reserved for those with significant PSA changes over time, or
      for those with clinical manifestations mandating immediate therapy. Using the PSA
      test to monitor disease progression or recurrence is appropriate, provided one
      understands that absolute levels of PSA are rarely meaningful; it is the relative
      change in PSA levels over time that provides insight, but not definitive proof of
      a cancerous condition necessitating therapy. PSA secretion is under hormonal
      control and thus PSA levels may be affected differently by the type of drug
      therapy, by the stage of a patients' disease, and by genetic factors suggesting
      some men are 'high PSA producers'. Until a validated alternative test for
      prostate cancer is found and adopted, the current flawed PSA test needs to be
      used more judiciously and not used for routine screening as studies have
      demonstrated that screening, as defined, does not lead to a reduction in patient
      mortality. All men, their families and their physicians need to understand the
      significant limitations of PSA testing.

PMID- 21861674
TI  - Deconstructing events: the neural bases for space, time, and causality.
AB  - Space, time, and causality provide a natural structure for organizing our
      experience. These abstract categories allow us to think relationally in the most
      basic sense; understanding simple events requires one to represent the spatial
      relations among objects, the relative durations of actions or movements, and the
      links between causes and effects. The present fMRI study investigates the extent
      to which the brain distinguishes between these fundamental conceptual domains.
      Participants performed a 1-back task with three conditions of interest (space,
      time, and causality). Each condition required comparing relations between events
      in a simple verbal narrative. Depending on the condition, participants were
      instructed to either attend to the spatial, temporal, or causal characteristics
      of events, but between participants each particular event relation appeared in
      all three conditions. Contrasts compared neural activity during each condition
      against the remaining two and revealed how thinking about events is deconstructed
      neurally. Space trials recruited neural areas traditionally associated with
      visuospatial processing, primarily bilateral frontal and occipitoparietal
      networks. Causality trials activated areas previously found to underlie causal
      thinking and thematic role assignment, such as left medial frontal and left
      middle temporal gyri, respectively. Causality trials also produced activations in
      SMA, caudate, and cerebellum; cortical and subcortical regions associated with
      the perception of time at different timescales. The time contrast, however,
      produced no significant effects. This pattern, indicating negative results for
      time trials but positive effects for causality trials in areas important for time
      perception, motivated additional overlap analyses to further probe relations
      between domains. The results of these analyses suggest a closer correspondence
      between time and causality than between time and space.

PMID- 21861675
TI  - The effects of aging on the neural basis of implicit associative learning in a
      probabilistic triplets learning task.
AB  - Few studies have investigated how aging influences the neural basis of implicit
      associative learning, and available evidence is inconclusive. One emerging
      behavioral pattern is that age differences increase with practice, perhaps
      reflecting the involvement of different brain regions with training. Many studies
      report hippocampal involvement early on with learning becoming increasingly
      dependent on the caudate with practice. We tested the hypothesis that the
      contribution of these regions to learning changes with age because of
      differential age-related declines in the striatum and hippocampi. We assessed age
      related differences in brain activation during implicit associative learning
      using the Triplets Learning Task. Over three event-related fMRI runs, 11 younger
      and 12 healthy older adults responded to only the third (target) stimulus in
      sequences of three stimuli ("triplets") by corresponding key press. Unbeknown to
      participants, the first stimulus' location predicted one target location for 80%
      of trials and another target location for 20% of trials. Both age groups learned
      associative regularities but differences in favor of the younger adults emerged
      with practice. The neural basis of learning (response to predictability) was
      examined by identifying regions that showed a greater response to triplets that
      occurred more frequently. Both age groups recruited the hippocampus early, but
      with training, the younger adults recruited their caudate whereas the older
      adults continued to rely on their hippocampus. This pattern enables older adults
      to maintain near-young levels of performance early in training, but not later,
      and adds to evidence that implicit associative learning is supported by different
      brain networks in younger and older adults.

PMID- 21861676
TI  - Amygdalar function reflects common individual differences in emotion and pain
      regulation success.
AB  - Although the co-occurrence of negative affect and pain is well recognized, the
      mechanism underlying their association is unclear. To examine whether a common
      self-regulatory ability impacts the experience of both emotion and pain, we
      integrated neuroimaging, behavioral, and physiological measures obtained from
      three assessments separated by substantial temporal intervals. Our results
      demonstrated that individual differences in emotion regulation ability, as
      indexed by an objective measure of emotional state, corrugator electromyography,
      predicted self-reported success while regulating pain. In both emotion and pain
      paradigms, the amygdala reflected regulatory success. Notably, we found that
      greater emotion regulation success was associated with greater change of
      amygdalar activity following pain regulation. Furthermore, individual differences
      in degree of amygdalar change following emotion regulation were a strong
      predictor of pain regulation success, as well as of the degree of amygdalar
      engagement following pain regulation. These findings suggest that common
      individual differences in emotion and pain regulatory success are reflected in a
      neural structure known to contribute to appraisal processes.

PMID- 21861677
TI  - Depth of conceptual knowledge modulates visual processes during word reading.
AB  - Recent evidence suggests that conceptual knowledge modulates early visual stages
      of object recognition. The present study investigated whether similar modulations
      can be observed also for the recognition of object names, that is, for symbolic
      representations with only arbitrary relationships between their visual features
      and the corresponding conceptual knowledge. In a learning paradigm, we
      manipulated the amount of information provided about initially unfamiliar visual
      objects while controlling for perceptual stimulus properties and exposure. In a
      subsequent test session with electroencephalographic recordings, participants
      performed several tasks on either the objects or their written names. For objects
      as well as names, knowledge effects were observed as early as about 120 msec in
      the P1 component of the ERP, reflecting perceptual processing in extrastriate
      visual cortex. These knowledge-dependent modulations of early stages of visual
      word recognition suggest that information about word meanings may modulate the
      perception of arbitrarily related visual features surprisingly early.

PMID- 21861678
TI  - Dissociable neural activations of conscious visibility and attention.
AB  - Recent neuroimaging evidence indicates that visual consciousness of objects is
      reflected by the activation in the lateral occipital cortex as well as in the
      frontal and parietal cortex. However, most previous studies used behavioral
      paradigms in which attention raised or enhanced visual consciousness (visibility
      or recognition performance). This co-occurrence made it difficult to reveal
      whether an observed cortical activation is related to visual consciousness or
      attention. The present fMRI study investigated the dissociability of neural
      activations underlying these two cognitive phenomena. Toward this aim, we used a
      visual backward masking paradigm in which directing attention could either
      enhance or reduce the object visibility. The participants' task was to report the
      level of subjective visibility for a briefly presented target object. The target
      was presented in the center with four flankers, which was followed by the same
      number of masks. Behavioral results showed that attention to the flankers
      enhanced the target visibility, whereas attention to the masks attenuated it. The
      fMRI results showed that the occipito-temporal sulcus increased activation in the
      attend flankers condition compared with the attend masks condition, and occipito
      temporal sulcus activation levels positively correlated with the target
      visibility in both attentional conditions. On the other hand, the inferior
      frontal gyrus and the intraparietal sulcus increased activation in both the
      attend flankers and attend masks compared with an attend neither condition, and
      these activation levels were independent of target visibility. Taken together,
      present results showed a clear dissociation in neural activities between
      conscious visibility and attention.

PMID- 21861679
TI  - The neural basis of reversible sentence comprehension: evidence from voxel-based
      lesion symptom mapping in aphasia.
AB  - We explored the neural basis of reversible sentence comprehension in a large
      group of aphasic patients (n = 79). Voxel-based lesion symptom mapping revealed a
      significant association between damage in temporo-parietal cortex and impaired
      sentence comprehension. This association remained after we controlled for
      phonological working memory. We hypothesize that this region plays an important
      role in the thematic or what-where processing of sentences. In contrast, we
      detected weak or no association between reversible sentence comprehension and the
      ventrolateral pFC, which includes Broca's area, even for syntactically complex
      sentences. This casts doubt on theories that presuppose a critical role for this
      region in syntactic computations.

PMID- 21861681
TI  - Theta dynamics reveal domain-specific control over stimulus and response
      conflict.
AB  - Cognitive control allows us to adjust to environmental changes. The medial
      frontal cortex (MFC) is thought to detect conflicts and recruit additional
      resources from other brain areas including the lateral prefrontal cortices. Here
      we investigated how the MFC acts in concert with visual, motor, and lateral
      prefrontal cortices to support adaptations of goal-directed behavior.
      Physiologically, these interactions may occur through local and long-range
      synchronized oscillation dynamics, particularly in the theta range (4-8 Hz). A
      speeded flanker task allowed us to investigate conflict-type-specific control
      networks for perceptual and response conflicts. Theta power over MFC was
      sensitive to both perceptual and response conflict. Interareal theta phase
      synchrony, however, indicated a selective enhancement specific for response
      conflicts between MFC and left frontal cortex as well as between MFC and the
      presumed motor cortex contralateral to the response hand. These findings suggest
      that MFC theta-band activity is both generally involved in conflict processing
      and specifically involved in linking a neural network controlling response
      conflict.

PMID- 21861680
TI  - Executive semantic processing is underpinned by a large-scale neural network:
      revealing the contribution of left prefrontal, posterior temporal, and parietal
      cortex to controlled retrieval and selection using TMS.
AB  - To understand the meanings of words and objects, we need to have knowledge about
      these items themselves plus executive mechanisms that compute and manipulate
      semantic information in a task-appropriate way. The neural basis for semantic
      control remains controversial. Neuroimaging studies have focused on the role of
      the left inferior frontal gyrus (LIFG), whereas neuropsychological research
      suggests that damage to a widely distributed network elicits impairments of
      semantic control. There is also debate about the relationship between semantic
      and executive control more widely. We used TMS in healthy human volunteers to
      create "virtual lesions" in structures typically damaged in patients with
      semantic control deficits: LIFG, left posterior middle temporal gyrus (pMTG), and
      intraparietal sulcus (IPS). The influence of TMS on tasks varying in semantic and
      nonsemantic control demands was examined for each region within this hypothesized
      network to gain insights into (i) their functional specialization (i.e.,
      involvement in semantic representation, controlled retrieval, or selection) and
      (ii) their domain dependence (i.e., semantic or cognitive control). The results
      revealed that LIFG and pMTG jointly support both the controlled retrieval and
      selection of semantic knowledge. IPS specifically participates in semantic
      selection and responds to manipulations of nonsemantic control demands. These
      observations are consistent with a large-scale semantic control network, as
      predicted by lesion data, that draws on semantic-specific (LIFG and pMTG) and
      domain-independent executive components (IPS).

PMID- 21861682
TI  - Early human visual cortex encodes surface brightness induced by dynamic context.
AB  - Visual scene perception owes greatly to surface features such as color and
      brightness. Yet, early visual cortical areas predominantly encode surface
      boundaries rather than surface interiors. Whether human early visual cortex may
      nevertheless carry a small signal relevant for surface perception is a topic of
      debate. We induced brightness changes in a physically constant surface by
      temporally modulating the luminance of surrounding surfaces in seven human
      participants. We found that fMRI activity in the V2 representation of the
      constant surface was in antiphase to luminance changes of surrounding surfaces
      (i.e., activity was in-phase with perceived brightness changes). Moreover, the
      amplitude of the antiphase fMRI activity in V2 predicted the strength of illusory
      brightness perception. We interpret our findings as evidence for a surface
      related signal in early visual cortex and discuss the neural mechanisms that may
      underlie that signal in concurrence with its possible interaction with the
      properties of the fMRI signal.

PMID- 21861683
TI  - Attentional capture by salient distractors during visual search is determined by
      temporal task demands.
AB  - The question whether attentional capture by salient but task-irrelevant visual
      stimuli is triggered in a bottom-up fashion or depends on top-down task settings
      is still unresolved. Strong support for bottom-up capture was obtained in the
      additional singleton task, in which search arrays were visible until response
      onset. Equally strong evidence for top-down control of attentional capture was
      obtained in spatial cueing experiments in which display durations were very
      brief. To demonstrate the critical role of temporal task demands on salience
      driven attentional capture, we measured ERP indicators of capture by task
      irrelevant color singletons in search arrays that could also contain a shape
      target. In Experiment 1, all displays were visible until response onset. In
      Experiment 2, display duration was limited to 200 msec. With long display
      durations, color singleton distractors elicited an N2pc component that was
      followed by a late Pd component, suggesting that they triggered attentional
      capture, which was later replaced by location-specific inhibition. When search
      arrays were visible for only 200 msec, the distractor-elicited N2pc was
      eliminated and was replaced by a Pd component in the same time range, indicative
      of rapid suppression of capture. Results show that attentional capture by salient
      distractors can be inhibited for short-duration search displays, in which it
      would interfere with target processing. They demonstrate that salience-driven
      capture is not a purely bottom-up phenomenon but is subject to top-down control.

PMID- 21861684
TI  - Dynamic facial expressions evoke distinct activation in the face perception
      network: a connectivity analysis study.
AB  - Very little is known about the neural structures involved in the perception of
      realistic dynamic facial expressions. In the present study, a unique set of
      naturalistic dynamic facial emotional expressions was created. Through fMRI and
      connectivity analysis, a dynamic face perception network was identified, which is
      demonstrated to extend Haxby et al.'s [Haxby, J. V., Hoffman, E. A., & Gobbini,
      M. I. The distributed human neural system for face perception. Trends in
      Cognitive Science, 4, 223-233, 2000] distributed neural system for face
      perception. This network includes early visual regions, such as the inferior
      occipital gyrus, which is identified as insensitive to motion or affect but
      sensitive to the visual stimulus, the STS, identified as specifically sensitive
      to motion, and the amygdala, recruited to process affect. Measures of effective
      connectivity between these regions revealed that dynamic facial stimuli were
      associated with specific increases in connectivity between early visual regions,
      such as the inferior occipital gyrus and the STS, along with coupling between the
      STS and the amygdala, as well as the inferior frontal gyrus. These findings
      support the presence of a distributed network of cortical regions that mediate
      the perception of different dynamic facial expressions.

PMID- 21861685
TI  - Distinct contributions of the magnocellular and parvocellular visual streams to
      perceptual selection.
AB  - During binocular rivalry, conflicting images presented to the two eyes compete
      for perceptual dominance, but the neural basis of this competition is disputed.
      In interocular switch rivalry, rival images periodically exchanged between the
      two eyes generate one of two types of perceptual alternation: (1) a fast, regular
      alternation between the images that is time-locked to the stimulus switches and
      has been proposed to arise from competition at lower levels of the visual
      processing hierarchy or (2) a slow, irregular alternation spanning multiple
      stimulus switches that has been associated with higher levels of the visual
      system. The existence of these two types of perceptual alternation has been
      influential in establishing the view that rivalry may be resolved at multiple
      hierarchical levels of the visual system. We varied the spatial, temporal, and
      luminance properties of interocular switch rivalry gratings and found, instead,
      an association between fast, regular perceptual alternations and processing by
      the magnocellular stream and between slow, irregular alternations and processing
      by the parvocellular stream. The magnocellular and parvocellular streams are two
      early visual pathways that are specialized for the processing of motion and form,
      respectively. These results provide a new framework for understanding the neural
      substrates of binocular rivalry that emphasizes the importance of parallel visual
      processing streams, and not only hierarchical organization, in the perceptual
      resolution of ambiguities in the visual environment.

PMID- 21861686
TI  - Explicit and implicit second language training differentially affect the
      achievement of native-like brain activation patterns.
AB  - It is widely believed that adults cannot learn a foreign language in the same way
      that children learn a first language. However, recent evidence suggests that
      adult learners of a foreign language can come to rely on native-like language
      brain mechanisms. Here, we show that the type of language training crucially
      impacts this outcome. We used an artificial language paradigm to examine
      longitudinally whether explicit training (that approximates traditional grammar
      focused classroom settings) and implicit training (that approximates immersion
      settings) differentially affect neural (electrophysiological) and behavioral
      (performance) measures of syntactic processing. Results showed that performance
      of explicitly and implicitly trained groups did not differ at either low or high
      proficiency. In contrast, electrophysiological (ERP) measures revealed striking
      differences between the groups' neural activity at both proficiency levels in
      response to syntactic violations. Implicit training yielded an N400 at low
      proficiency, whereas at high proficiency, it elicited a pattern typical of native
      speakers: an anterior negativity followed by a P600 accompanied by a late
      anterior negativity. Explicit training, by contrast, yielded no significant
      effects at low proficiency and only an anterior positivity followed by a P600 at
      high proficiency. Although the P600 is reminiscent of native-like processing,
      this response pattern as a whole is not. Thus, only implicit training led to an
      electrophysiological signature typical of native speakers. Overall, the results
      suggest that adult foreign language learners can come to rely on native-like
      language brain mechanisms, but that the conditions under which the language is
      learned may be crucial in attaining this goal.

PMID- 21861687
TI  - Potential adverse effects of oseltamivir in rats: males are more vulnerable than
      females.
AB  - Oseltamivir is the most widely used antiviral drug for the treatment and
      prophylaxis of influenza. However, not much is known about its adverse effects.
      The potential side effects were investigated in male and female rats (140-170 g).
      Oseltamivir was administered at 2.2 mg.kg(-1).day(-1) for 5 days. For both
      genders, treatment with oseltamivir resulted in significant reductions in the
      hepatic activities of glutathione reductase, glutathione peroxidase, and
      glutathione S-transferase. Also for both genders, oseltamivir produced modest
      reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone
      oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic
      glutathione content. For both genders, neither the kidney functions nor protein
      profile was affected by oseltamivir. Oseltamivir also caused significant
      elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the
      activity of gamma-glutamyl transpeptidase, in both genders. For male animals
      only, oseltamivir treatment elevated the serum level of total cholesterol as well
      as the activity of serum alanine aminotransferase, and reduced the hepatic
      activities of superoxide dismutase and catalase. Oseltamivir caused oxidative
      stress and acute toxicity in the liver, and disrupted the cholesterol and lipid
      metabolism but was less likely to cause serious drug interactions. There was a
      sexual differentiation in these adverse effects, with adverse effects being more
      evident in male rats. 

PMID- 21861688
TI  - The tunica adventitia of human arteries and veins as a source of mesenchymal stem
      cells.
AB  - We previously demonstrated that human pericytes, which encircle capillaries and
      microvessels, give rise in culture to genuine mesenchymal stem cells (MSCs). This
      raised the question as to whether all MSC are derived from pericytes. Pericytes
      and other cells defined on differential expression of CD34, CD31, and CD146 were
      sorted from the stromal vascular fraction of human white adipose tissue. Besides
      pericytes, CD34+ CD31- CD146- CD45- cells, which reside in the outmost layer of
      blood vessels, the tunica adventitia, natively expressed MSC markers and gave
      rise in culture to clonogenic multipotent progenitors identical to standard bone
      marrow-derived MSC. Despite common MSC features and developmental properties,
      adventitial cells and pericytes retain distinct phenotypes and genotypes through
      culture. However, in the presence of growth factors involved in vascular
      remodeling, adventitial cells acquire a pericytes-like phenotype. In conclusion,
      we demonstrate the co-existence of 2 separate perivascular MSC progenitors:
      pericytes in capillaries and microvessels and adventitial cells around larger
      vessels.

PMID- 21861689
TI  - Reduced oxygen concentration enhances conversion of embryonic stem cells to
      epiblast stem cells.
AB  - Recently, an additional type of pluripotent stem cell-line derived from mouse
      embryos has been established and termed epiblast stem cell (EpiSC), and is
      expected to be an important tool for studying the mechanisms of maintenance of
      pluripotency since they depend on basic fibroblast growth factor-MAPK and Activin
      A-Smad2/3 signaling to maintain pluripotency, unlike mouse embryonic stem cells
      (ESCs). Further, because of the similarities between mouse EpiSCs and human ESCs,
      EpiSCs are expected to be effective experimental models for human stem cell
      therapy. Recently, study for conversion from ESC state to EpiSC state or
      reversion from EpiSC state to ESC state has attracted interest since these
      techniques may lead to increasing the potential of pluripotent stem cells and our
      knowledge about their developmental status. In the present study, we find that a
      low oxygen concentration in culture environment accelerated, improved, and
      stabilized the EpiSC state of the converted cells from the ESC state using
      Oct4DeltaPE-GFP transgenic ESCs. Induced EpiSCs (iEpiSCs) in hypoxia possess
      closer gene expression patterns to native EpiSCs, and bisulfite sequences for the
      promoter regions of Stella and Oct4 genes have elucidated that the iEpiSC gain
      EpiSC-specific methylation patterns in hypoxia. Our data provide evidence that
      oxygen concentration is an important factor for establishment of the EpiSC
      specific state.

PMID- 21861690
TI  - Phantom pain reduction by low-frequency and low-intensity electromagnetic fields.
AB  - Although various treatments have been presented for phantom pain, there is little
      proof supporting the benefits of pharmacological treatments, surgery or
      interventional techniques, electroconvulsive therapy, electrical nerve
      stimulation, far infrared ray therapy, psychological therapies, etc. Here, we
      report the preliminary results for phantom pain reduction by low-frequency and
      intensity electromagnetic fields under clinical circumstances. Our method is
      called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with
      phantom limb pain participated. The patients were treated using a pre-programmed,
      six sessions. Pain intensity was quantified upon admission using a 0-10 verbal
      numerical rating scale. Most of the patients (n = 10) reported a marked reduction
      in the intensity of phantom limb pain. Several patients also reported about
      improvement in their sleep and mood quality, or a reduction in the frequency of
      phantom pain after the treatments. No improvements in the reduction of phantom
      limb pain or sleep and mood improvement were reported in the control group (n =
      5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic
      application in the reduction of phantom limb pain. Here, we also suggest that
      some of the possible effects of the EMOST may be achieved via the redox balance
      of the body and redox-related neural plasticity.

PMID- 21861691
TI  - Selective destabilization of tumor cells with pulsed electric and magnetic
      sequences: a preliminary report.
AB  - BACKGROUND: Various studies in vitro suggest that low electric and magnetic
      fields may modify cancer cell growth and recent studies in vivo have revealed
      anti-tumoral effects. After screening different tumor cell lines, we identified
      specific sequences of localized magnetic and electric fields (MESQ) that reduce
      cancer cell survival in vitro. This finding led us to design an experiment to
      determine the actual efficacy of above sequences in selectively destabilizing
      tumor cells and their effect on healthy cells. MATERIALS AND METHODS: We exposed
      the MCF7 cancer cell line and normal fibroblasts to MESQ for 1, 2, 3 and 6 hours,
      evaluating cell survival and induction of apoptosis. RESULTS: Exposure to MESQ
      reduced MCF7 survival, inducing apoptosis in a timedependent way, whereas
      fibroblasts were completely unaffected. CONCLUSION: These results have promising
      implications for the treatment of cancer and warrant further research.

PMID- 21861692
TI  - Electromagnetic energy absorption patterns in subjects with common visual
      disorders.
AB  - This article describes the analysis of electromagnetic energy absorption
      properties of models of the human eye with common visual disorders. The
      investigation addresses two types of visual disorders, namely hyperopia (or
      farsightedness) and myopia (or nearsightedness). Calculations were carried out
      using plane multilayered method with common wireless communication frequencies of
      900, 1800, and 2450 MHz. The effect of wireless radiation on the eye is studied
      by calculation of the specific absorption rate (SAR) in three different eye
      models. The results of the simulations confirmed the anticipated and more complex
      relationship between absorption and structural variations of the eye at these
      frequencies.

PMID- 21861693
TI  - Effects of sinusoidal electromagnetic fields on histopathology and structures of
      brains of preincubated white Leghorn chicken embryos.
AB  - There are several reports indicating linkages between exposures to 50-60 Hz
      electromagnetic fields and abnormalities in the early stages of chicken embryonic
      development. Based on our previous published research carried out at the
      Department of Animal Sciences, Faculty of Biological Sciences, Shahid Beheshti
      University, effects of sinusoidal electromagnetic fields on histopathology and
      structures of brains of preincubated white leghorn hen eggs were investigated.
      Three hundred healthy fresh fertilized eggs (55-65 gr) were divided into three
      groups of experimental (n = 50), control (n = 75), and sham (n = 75).
      Experimental eggs (inside the coil) were exposed to 3 different intensities of
      1.33, 2.66, and 7.32 mT and sham groups were located inside the same coil with no
      exposure, for 24 h before incubation. Control, sham, and experimental groups were
      all incubated in an incubator (38 +/- 0.5( degrees )C, 60% humidity) for 14 days.
      14-day old chicken embryos were removed by C-sections, and the brains of all
      embryos of all groups were fixed in formalin(10%), stained with H&E and TUNEL
      assay, for studying the histopatholog and process of apoptosis. The brains of
      other embryos were prepared for Scanning Electeron Microscope. Results showed
      electromagnetic fields have toxic effects on brain cells by increasing the number
      of apoptotic cells and degeneration of brains' tissues of exposed chicken
      embryos. These findings suggest that the electromagnetic fields induce brain
      damages at different levels.

PMID- 21861694
TI  - Effects of 50 Hz electromagnetic fields on the histology, apoptosis, and
      expression of c-Fos and beta-catenin on the livers of preincubated white Leghorn
      chicken embryos.
AB  - Reports have demonstrated occurrences of abnormalities in the early stages of
      chicken embryonic development due to the exposure to electromagnetic fields
      (EMFs). This article was designed to investigate the effects of sinusoidal EMF on
      the histopathology, apoptosis, and expressions of c-Fos and beta-Catenin genes of
      the livers of preincubated White Leghorn chicken embryos, based on our published
      experiments. 300 healthy, fresh fertilized eggs were divided into control (n =
      70), sham (n = 70), and four experimental (1-4,days 13, 14, 5, and 19, n = 40)
      groups. Experimental eggs were exposed to the most effective intensity in a coil
      with 7.32 mT density, and sham groups were also located in the same coil with no
      exposure, both for 24 h before incubation. Control, sham, and experimental groups
      were then incubated in an incubator (37 degrees C, humidity 60%) for 13,14,15,
      and 19 days. Livers of 13-15 and 19 day-old chicken embryos were removed by C
      section and fixed in formalin (10%), stained with Hematoxylin-Eosin and TUNEL for
      histopathological and apoptosis studies. Others were used for investigating c-Fos
      and beta-Catenin expressions, using RT-PCR. Results showed extensive hemorrhages
      all over the chicken embryos' bodies and livers, more lymphoid tissues, disturbed
      parenchymal tissues, sinusoid denaturation, vesiculizad cytoplasm, an increase in
      the number of apoptotic cells, and a decrease on the levels of expressions of c
      Fos and beta-Catenin genes in experimental groups of 1-4, comparing control and
      sham groups.

PMID- 21861695
TI  - Acute effect of exposure of mollusk single neuron to 900-MHz mobile phone
      radiation.
AB  - The goal of the present work was to explore the influence of commercially
      available cell phone irradiation on the single neuron excitability and memory
      processes. A Transverse Electromagnetic Cell (TEM Cell) was used to expose single
      neurons of mollusk to the electromagnetic field. Finite-Difference Time-Domain
      (FDTD) method was used for modeling the TEM Cell and the electromagnetic field
      interactions with living nerve ganglion and neurons. Neuron electrophysiology was
      investigated using standard microelectrode technique. The specific absorption
      rate (SAR) deposited into the single neuron was calculated to be 0.63 W/kg with a
      temperature increment of 0.1 degrees C. After acute exposure, average firing
      threshold of the action potentials was not changed. However, the average latent
      period was significantly decreased. This indicates that together with latent
      period the threshold and the time of habituation might be altered during
      exposure. However, these alterations are transient and only latent period remains
      on the changed level.

PMID- 21861698
TI  - An introduction to the special issue on "cytokines and autoimmune diseases".

PMID- 21861697
TI  - Association between two genetic variants in miRNA and primary liver cancer risk
      in the Chinese population.
AB  - MicroRNAs (miRNAs) play an important role in the growth and development of human
      beings. Single nucleotide polymorphisms (SNPs) within miRNA could change their
      production or affinity with target genes, thus leading to malignant diseases.
      This case-control study conducted in Western China aimed to explore the
      relationship between polymorphisms in miR-146a (rs2910164 G>C) and miR-499
      (rs3746444 T>C) and primary liver cancers in the Chinese population. 186 primary
      liver cancer cases and 483 healthy controls were genotyped using polymerase chain
      reaction-restriction fragment length polymorphism. No significant differences
      were observed between distributions of the two SNPs and susceptibility of primary
      liver cancer or diverse clinicopathologic features. However, we found that
      patients with genotype CG of the SNP in miR-146a tended to have earlier onset and
      better liver function than patients with genotype CC (average age: 49.9 vs. 54.9,
      p=0.038; average Child-Pugh grade: 5.55 vs. 6.15, p=0.021), and further analysis
      showed that patients who had at least one G allele were diagnosed at an earlier
      age (average age: 49.6 vs. 54.9, p=0.022) and had better liver function (average
      Child-Pugh grade:5.60 vs. 6.15, p=0.026). Our data suggested lack of association
      between the two SNPs and primary liver cancer risk, though, interestingly, the
      miR-146a SNP may influence the age of onset and Child-Pugh grade.

PMID- 21861696
TI  - Calcium and reactive oxygen species in acute pancreatitis: friend or foe?
AB  - SIGNIFICANCE: Acute pancreatitis (AP) is a debilitating and, at times, lethal
      inflammatory disease, the causes and progression of which are incompletely
      understood. Disruption of Ca(2+) homeostasis in response to precipitants of AP
      leads to loss of mitochondrial integrity and cellular necrosis. RECENT ADVANCES:
      While oxidative stress has been implicated as a major player in the pathogenesis
      of this disease, its precise roles remain to be defined. Recent developments are
      challenging the perception of reactive oxygen species (ROS) as nonspecific
      cytotoxic agents, suggesting that ROS promote apoptosis that may play a vital
      protective role in cellular stress since necrosis is avoided. CRITICAL ISSUES:
      Fresh clinical findings have indicated that antioxidant treatment does not
      ameliorate AP and may actually worsen the outcome. This review explores the
      complex links between cellular Ca(2+) signaling and the intracellular redox
      environment, with particular relevance to AP. FUTURE DIRECTIONS: Recent
      publications have underlined the importance of both Ca(2+) and ROS within the
      pathogenesis of AP, particularly in the determination of cell fate. Future
      research should elucidate the subtle interplay between Ca(2+) and redox
      mechanisms that operate to modulate mitochondrial function, with a view to
      devising strategies for the preservation of organellar function.

PMID- 21861699
TI  - Critical cytokine pathways to cardiac inflammation.
AB  - Infectious disease is frequently cited as a precursor of subsequent autoimmune
      disease in genetically susceptible hosts. However, the precise mechanisms
      required for the transition from infection to autoimmunity have not been well
      defined. We have developed a mouse model of autoimmune myocarditis initiated by
      infection with Coxsackievirus B3 to trace the cytokine pathways involved. We
      found that greater production of interleukin-1beta (IL-1beta) and tumor necrosis
      factor-alpha during the early innate response to virus infection is necessary and
      sufficient to induce a later heart-specific autoimmune disease. Severity of the
      autoimmune myocarditis is determined by the profile of a number of T helper 1
      (Th1) and Th2 cytokines. Th2 responses are especially pronounced in the most
      severe forms of myocarditis where eosinophils are prominent. The Th1 pathway can
      lead to infiltration of the heart, but may be dampened by concurrent INF-gamma
      production. Th17 cytokines also contribute to disease, but the signature Th17
      cytokine, IL-17A, is not required for cardiac inflammation. Rather, IL-17A is
      needed for progression to dilated cardiomyopathy. These findings may provide
      useful markers to identify individuals prone to develop an autoimmune sequel
      after infection and suggest future early interventions.

PMID- 21861701
TI  - Armenia 1988 earthquake and telemedicine: lessons learned and forgotten.
AB  - PURPOSE: To showcase the observations and lessons learned from the first large
      scale international telemedicine program addressing the medical and health
      consequences of disasters. BACKGROUND: Almost 24 years ago a major earthquake
      devastated the northwestern region of Soviet Armenia. The National Aeronautics
      and Space Administration deployed a telemedicine spacebridge, which operated
      uninterrupted for 3 months, extending its services to the remote region of Ufa to
      help the burn victims, mostly children, from a railroad explosion accident.
      Expert consultations were provided by four major medical center from the United
      States and several military and civilian medical services of the Soviet Union.
      LESSONS LEARNED: Disasters continue to contribute to increased morbidity and
      mortality with significant economic impacts worldwide. Psychological, physical,
      and social sequelae persist years after the events. Many pre-existing
      socioeconomic conditions are aggravated following disasters. Telemedicine is a
      useful medical and public health technology that continues to be underutilized
      due to the lack of inclusion in the preparedness planning, training, availability
      of networks, and connectivity costs. POLICY IMPLICATIONS: Natural and human-made
      disasters require both near-term and long-term interventions to reduce morbidity
      and mortality among the surviving victims. Telemedicine, information technology,
      and modern portable communication devices should be incorporated in disaster
      preparedness and recovery training and operations.

PMID- 21861700
TI  - Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells
      through the repression of the microRNA-200 family.
AB  - Expression of the transcription factor Snail is required for normal
      vasculogenesis in the developing mouse embryo. In addition, tumors expressing
      Snail have been associated with a more malignant phenotype, with both increased
      invasive properties and angiogenesis. Although the relationship between Snail and
      vasculogenesis has been noted, no mechanistic analysis has been elucidated. Here,
      we show that in addition to inducing an epithelial mesenchymal transition, Snail
      promotes the cell-autonomous induction of Flk1(+) endothelial cells in an early
      subset of differentiating mouse embryonic stem (ES) cells. Cells that become
      Flk1+ in response to Snail have a transcriptional profile specific to
      Gata6+primitive endoderm, but not the early Nanog+epiblast. We further show that
      Snail's ability to promote Flk1(+) endothelium depends on fibroblast growth
      factor signaling as well as the repression of the microRNA-200 (miR-200) family,
      which directly targets the 3' UTRs of Flk1 and Ets1. Together, our results show
      that Snail is capable of inducing Flk1+ lineage commitment in a subset of
      differentiating ES cells through the down-regulation of the miR-200 family. We
      hypothesize that this mechanism of Snail-induced vasculogenesis may be conserved
      in both the early developing embryo and malignant cancers.

PMID- 21861703
TI  - Inhibition of aflatoxin production and growth of Aspergillus parasiticus by
      Cuminum cyminum, Ziziphora clinopodioides, and Nigella sativa essential oils.
AB  - Aflatoxins are highly toxic and carcinogenic metabolites produced by Aspergillus
      parasiticus on food and agricultural commodities. Natural products may control
      the production of aflatoxins. The aims of this study were to evaluate the effects
      of the essential oils (EOs) of Cuminum cyminum, Ziziphora clinopodioides, and
      Nigella sativa on growth and aflatoxins production by A. parasiticus. Minimal
      inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs) of
      the EOs were determined and compared with each other. Determination of aflatoxins
      (AFB(1), AFB(2), AFG(1), and AFG(2)) was performed by immunoaffinity column
      extraction using reverse phase-high performance liquid chromatography. The major
      oil components were alpha-pinene (30%) in C. cyminum, pulegone (37%) in Z.
      clinopodioides, and trans-anthol (38.9%) in N. sativa oils. In broth
      microdilution method, C. cyminum oil exhibited the strongest activity (MIC(90):
      1.6; MFC: 3.5 mg/mL), followed by Z. clinopodioides (MIC(90): 2.1; MFC: 5.5
      mg/mL) and N. sativa (MIC(90): 2.75; MFC: 6.25 mg/mL) oils against A. parasiticus
      (p<0.05). Aflatoxin production was inhibited at 0.25 mg/mL of C. cyminum and Z.
      clinopodioides oils, of which that of C. cyminum was a stronger inhibitor. C.
      cyminum EO caused significant reductions in values of 94.2% for AFB(1), 100% for
      AFB(2), 98.9% for AFG(1), 100% for AFG(2), and 97.5% for total aflatoxin. It is
      concluded that the EOs of C. cyminum, Z. clinopodioides, and N. sativa could be
      used as natural inhibitors in foods at low concentrations to protect from fungal
      and toxin contaminations by A. parasiticus.

PMID- 21861704
TI  - Reduction of Escherichia coli on surfaces of utensils and development of a
      predictive model as a function of concentration and exposure time of chlorine.
AB  - Cross-contamination to fruit and vegetables can readily occur through
      contaminated surfaces; thus, there is a need to develop methods to inactivate
      microorganisms on the surfaces of various materials. The aim of this study was to
      develop methods to reduce the levels of Escherichia coli on the surfaces of
      various materials and to develop a predictive model as a function of chlorine
      concentration and exposure time. The reduction of E. coli on the surfaces of
      stainless steel, plastic, wood, rubber, glass, and ceramic at various chlorine
      concentrations (0-200 ppm) after a 0-5-min exposure was evaluated. The surface
      treatment at the maximum chlorine concentration (200 ppm) over a 5-min exposure
      reduced the E. coli contamination levels to 5.30, 5.18, 3.34, 4.69, 5.05, and
      5.53 log CFU/cm(2) on the surfaces of stainless steel, plastic, wood, rubber,
      glass, and ceramic, respectively. Using these results, predictive models for the
      reduction of E. coli on surfaces of various materials using chlorine treatment
      were developed. Each model was significant (p<0.05) and defined as fit by the
      lack of fit and probability of normal residuals. It has measured the R(2) value
      to 0.9746. Therefore, the models presented in this study could be used to
      determine the minimum concentrations of chlorine and exposure times needed to
      control E. coli on the surfaces of various materials.

PMID- 21861705
TI  - Photodynamic therapy using an anti-EGF receptor antibody complexed with
      verteporfin nanoparticles: a proof of concept study.
AB  - Photodynamic therapy (PDT) is a noninvasive optical treatment method in which the
      topical or systemic delivery of photosensitizing drugs is followed by irradiation
      with broadband red light. Coupling photosensitizers with a specific antibody may
      allow this approach to target specific cancers. This study determines the
      antitumor efficacy of coupling verteporfin (Visudyne((r))), a hydrophobic
      polyporphryin oligomer, with an antiepidermal growth factor receptor (anti-EGFR)
      antibody. Poly[2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate
      co-p-nitrophenylcarbonyloxyethyl methacrylate] (PMBN) was conjugated with an anti
      EGFR antibody and mixed with verteporfin (verteporfin-PMBN-antibody complex).
      Tumor-bearing mice were intravenously injected with the verteporfin-PMBN-antibody
      complex or verteporfin plus PMBN without the antibody. Irradiation was conducted
      at 640 nm with a dose of 75 J/cm(2). The fluorescence intensity in A431 cells in
      vitro was threefold higher after exposure to verteporfin-PMBN-antibody complex
      than after exposure to verteporfin-PMBN. In A431 tumor-bearing mice, the
      intratumor concentration of verteporfin was 9.4 times higher than that of the
      skin, following administration of the verteporfin-PMBN-antibody complex. Tumor
      size significantly decreased within 8 days in mice treated with verteporfin-PMBN
      antibody complex compared with those treated with verteporfin-PMBN. PDT using a
      PMBN-verteporfin-antibody complex offers a promising anticancer therapy.

PMID- 21861706
TI  - Basic in vitro experiment on the adhesive effects of sheet-type hemostatic agents
      used in combination with a liquid fibrin sealant.
AB  - BACKGROUND AND PURPOSE: Various hemostatic agents have been used quite
      effectively for hemostasis, as well as for providing effective adhesion during
      laparoscopic partial nephrectomies. In this study, we investigated the
      adhesiveness to the renal tissue of some sheet-type hemostatic agents used in
      combination with a liquid fibrin sealant. MATERIALS AND METHODS: In Experiment A,
      component solutions of the fibrin glue (liquid fibrin sealant) were dripped onto
      a kite string placed annularly on a porcine kidney slice. Then, one of the sheet
      type hemostats--namely, the collagen, gelatin, or cellulose hemostat--was placed
      on the slices, and a string scale was used to measure the force needed to pull
      the string apart vertically from the kidney slice. Twelve slices were used for
      each group, and the weight data were analyzed statistically. The tissue adhering
      to each sheet-type hemostatic agent was fixed in formalin and sliced and then
      examined by light microscopy after hematoxylin and eosin staining. In Experiment
      B, the solutions were dripped onto the sheet-type hemostatic agent placed first
      on the slice, and the force needed for pulling apart the hemostat sheet from the
      slice was similarly examined. RESULTS: The combination of fibrin glue plus a
      collagen hemostat was clearly superior in Experiment A, but the hemostat and
      renal tissue could be pulled apart more easily in Experiment B. These results
      showed that fibrin glue could not exert its expected adhesive effect unless it is
      used in combination with another hemostatic agent or is directly applied to renal
      tissue. CONCLUSION: It is important to obtain further comparative data among
      agents and select the appropriate agents, taking into consideration the type of
      surgery.

PMID- 21861707
TI  - Down syndrome: parental origin, recombination, and maternal age.
AB  - The aims of the present study were to assess (1) the parental origin of trisomy
      21 and the stage in which nondisjunction occurs and (2) the relationship between
      altered genetic recombination and maternal age as risk factors for trisomy 21.
      The study included 102 cases with Down syndrome from the Croatian population.
      Genotyping analyses were performed by polymerase chain reaction using 11 short
      tandem repeat markers along chromosome 21q. The vast majority of trisomy 21 was
      of maternal origin (93%), followed by paternal (5%) and mitotic origin (2%). The
      frequencies of maternal meiotic I (MI) and meiotic II errors were 86% and 14%,
      respectively. The highest proportion of cases with zero recombination was
      observed among those with maternal MI derived trisomy 21. A higher proportion of
      telomeric exchanges were presented in cases with maternal MI errors and cases
      with young mothers, although these findings were not statistically significant.
      The present study is the first report examining parental origin and altered
      genetic recombination as a risk factor for trisomy 21 in a Croatian population.
      The results support that trisomy 21 has a universal genetic etiology across
      different human populations.

PMID- 21861708
TI  - Vascular behcet and mutations in thrombogenic genes: methylene tetrahydrofolate
      reductase, factor V, and prothrombin.
AB  - Vasculitis, thrombophlebitis, arterial aneurysms, and occlusions occur in about
      25% of patients with Behcet's disease (BD). The common inherited gene defects,
      factor V (FV) 1691A (Leiden), methylene tetrahydrofolate reductase (MTHFR) 677T,
      and prothrombin 20210A, are known risk factors for thrombosis. The aim of the
      study was to evaluate the contribution of these mutations to thrombosis in
      Israeli patients with BD. Fifty-four patients with BD (n=54; 27 men and 27 women)
      underwent clinical and genetic evaluation. Most patients (n=43; 79.6%) were of
      Arab descent (31 sporadic and 12 familial cases from 4 families), and 11 patients
      (20.4%) were of Jewish descent (all sporadic cases). The FV Leiden mutation was
      identified in five patients (9.2%), and eight patients were MTHFR 677TT
      homozygotes (14.8%). None had the 20210A mutant prothrombin allele. No
      statistical differences between carriers and noncarriers with regards to
      demographic and disease manifestations were calculated. Arabs were diagnosed
      earlier than Jewish patients (25.8+/-11.6 compared with 37.2+/-10.7, p=0.01,
      respectively), but Jewish patients had, respectively, more events of deep vein
      thrombosis (DVT) compared with Arabs (3 of 11, 27.3% and 3 of 43, 7%, p=0.09).
      Thrombotic events in our patients with BD were not associated with variations in
      thrombophilic genes.

PMID- 21861709
TI  - Associations of receptor for advanced glycation end products -374 T/A and Gly82
      Ser and peroxisome proliferator-activated receptor gamma Pro12Ala polymorphisms
      in Turkish coronary artery disease patients.
AB  - AIM: The aim of the present study was to investigate the individual and combined
      effects of receptor for advanced glycation end products (RAGE) -374T/A, RAGE
      Gly82Ser, and peroxisome proliferator-activated receptor gamma (PPAR-gamma)
      Pro12Ala polymorphisms on the development of coronary artery disease (CAD).
      MATERIALS AND METHODS: This study was carried out in 87 patients with CAD and 52
      CAD-free healthy controls. Polymerase chain reaction, restriction fragment length
      polymorphism, and agarose gel electrophoresis techniques were used to determine
      RAGE -374T/A, RAGE Gly82 Ser, and PPAR-gamma Pro12 Ala. RESULTS: Individual
      allele and genotype frequencies of RAGE -374T/A, RAGE Gly82Ser, and PPAR-gamma
      Pro12Ala polymorphisms were not significantly different between study groups.
      However, compared with the control group, wild-type T allele frequency was found
      to be higher in patients with diabetes (p=0.009). To investigate the combined
      effects of RAGE and PPAR polymorphisms, haplotype analysis was elevated and there
      was no statistical difference between the haplotypes of RAGE Gly82Ser with RAGE
      374T/A or PPAR Pro12Ala. However, the frequency of RAGE-374T/PPAR12Ala haplotype
      was found to be higher in both the patient group (p=0.024) and in patients
      without diabetes (p=0.037). CONCLUSION: The results of the present study
      demonstrated that possessing the A allele of RAGE -374T/A polymorphism by
      diabetic CAD patients and possessing the-374T/Ala12 haplotype of RAGE -374T/A and
      PPAR-gamma Pro12 Ala polymorphisms by the patients group were the most important
      risk factors for CAD.

PMID- 21861710
TI  - A novel DRD2 single-nucleotide polymorphism associated with schizophrenia
      predicts age of onset: HapMap tag-single-nucleotide polymorphism analysis.
AB  - BACKGROUND: Dopamine D2 receptor (DRD2) is thought to be critical in regulating
      the dopaminergic pathway in the brain, which is known to be important in the
      etiology of schizophrenia. It is, therefore, not surprising that most
      antipsychotic medication acts on DRD2. DRD2 is widely expressed in the brain;
      levels are reduced in the brains of patients with schizophrenia, and DRD2
      polymorphisms have been associated with reduced brain expression. We have
      previously identified a genetic variant in DRD2, rs6277 to be strongly implicated
      in schizophrenia susceptibility. METHODS: To identity new associations in the
      DRD2 gene with disease status and clinical severity, we genotyped seven single
      nucleotide polymorphisms (SNPs) in DRD2 by using a multiplex mass spectrometry
      method. SNPs were chosen by using a haplotype block-based gene-tagging approach;
      so, the entire DRD2 gene was represented. RESULTS: One polymorphism, rs2734839
      was found to be significantly associated with schizophrenia as well as late onset
      age. Individuals carrying the genetic variation were more than twice as likely to
      have schizophrenia compared with controls. CONCLUSIONS: Our results suggest that
      DRD2 genetic variation is a good indicator for schizophrenia risk and may also be
      used as a predictor of age of onset.

PMID- 21861711
TI  - Interleukin-10 (-1082G/A) gene polymorphism in patients with type 2 diabetes with
      and without nephropathy.
AB  - OBJECTIVE: Interleukin (IL)-10 is a major anti-inflammatory cytokine that plays a
      crucial role in the regulation of the immune system. IL-10 has met the criteria
      for an anti-inflammatory and an immunosuppressive cytokine, its activity may be
      important for clinical outcome of diabetic nephropathy (DN). We aimed at
      evaluating the relation between the genotypic and allelic frequencies of the IL
      10 (-1082G/A) polymorphisms, and their association with the risk to develop DN in
      the Turkish population. RESEARCH DESIGN AND METHODS: The (IL)-10 (-1082G/A)
      genotypes were retrospectively determined in 43 patients with nephropathy and 48
      without nephropathy and a control group of 112 healthy individuals. The
      polymorphisms were analyzed by polymerase chain reaction restriction fragment
      length polymorphism. RESULTS: This genotype distribution was different between
      control subjects and patients with type 2 diabetes in which 24.2% were AA, 75.8%
      were GA, and 0% were GG (p<0.001). The frequency of the mutant G allele was 36.1%
      in patients with diabetes nephropathy versus 39.6% in those without nephropathy
      (p>0.05). The genotype frequencies were AA, 27.9%; GA, 72.1%; and GG, 0% in
      patients with diabetes with nephropathy versus AA, 20.8%; GA, 79.2%; and GG, 0%
      in those without nephropathy (p>0.05). CONCLUSIONS: The polymorphisms of IL-10 (
      1082G/A) genes were significantly associated with the occurrence of patients with
      type 2 diabetes. The IL-10 (-1082G/A) genotype and allele frequencies were not
      different between patients with diabetes with nephropathy and those without
      nephropathy. Therefore, we conclude that the IL-10 (-1082G/A) gene polymorphism
      is not associated with the development of DN in Turkish patients with type 2
      diabetes.

PMID- 21861712
TI  - Prevalence of hemoglobinopathy disorders in adult patients sent for diagnosis of
      anemia in saudi arabia.
AB  - BACKGROUND: Hemoglobinopathies are a very heterogeneous group of congenital
      hemolytic anemia. AIM OF THE STUDY: Was to detect the prevalence of
      hemoglobinopathy disorders in adult patients sent for diagnosis of anemia by high
      performance liquid chromatography techniques in Saudi Arabia. SUBJECTS: A total
      of 329 blood samples from suspected cases with an average age of 39+/-6.49 of
      both sexes (140 men and 189 women) were included in the study. MAIN OUTCOME
      MEASURE: A total of 118 (35.9%) patients were found to have a normal pattern of
      hemoglobin (Hb)-electrophoresis with a mean level of HbA (alpha(2)beta(2))
      (97.0%+/-0.40%), HbA2 (alpha(2)delta(2)) (2.72%+/-0.55%), and HbF
      (alpha(2)gamma(2)) (0.59%+/-0.25%). One hundred twenty (36.5%) subjects were
      normal with iron deficiency masking the thalassemic trait (Hb: 8.71+/-1.7 g/dL,
      iron level: 3.62+/-2.7 MUg/dL, total iron-binding capacity: 86.9+/-21.5 MUg/dL).
      RESULTS: The remaining 91 (27.66%) patients showed different abnormal hemoglobin
      variants; 5 (1.5%) subjects had persistence of fetal HbF (7.12%+/-11.1%). Thirty
      three (10.0%) subjects had beta-thalassemia with a high level of HbA2 (>5.54%).
      Eleven (3.3%) had beta-thalassemic/sickle cell disease. Twenty-nine (8.8%) had
      sickle cell trait with a level of HbS alpha(2)beta(S)(2)<45%, and thirteen (4.0%)
      had sickle cell disease with a high level of HbS >=45%. CONCLUSION: beta
      thalassemia and sickle cell anemia are the most common monogenic disorders in
      Saudi Arabia. This is a serious health threat to our nation, if it is allowed to
      continue without taking preventive measures.

PMID- 21861713
TI  - Effects of in utero exposure to D-004, a lipid extract from Roystonea regia
      fruits, in the male rat: a comparison with finasteride.
AB  - D-004 is a lipid extract obtained from Cuban royal palm fruits, consisting of a
      mixture of free fatty acids, that prevents prostate hyperplasia induced with
      testosterone in rodents. This study investigated the possible alterations due to
      D-004 of androgen-dependent development after exposure in utero and compared them
      with those due to finasteride. Rats were randomized into five experimental
      groups: a control group, three groups treated with D-004 at 500, 750, or 1,000
      mg/kg/day, respectively, and a group treated with finasteride (10 mg/kg/day).
      Male rats were treated 10 weeks before and during mating. Female rats were
      treated for 15 days prior mating, during mating, during pregnancy, and until
      lactation (day 21) except for those treated with finasteride, which were only
      administered the drug on gestational days 12-21. All male offspring were
      monitored individually until necropsy after postnatal day 90. The results of the
      present study indicate that D-004 induced no alterations in androgen-dependent
      development after the exposure in utero. Also, the current study demonstrated a
      permanent reduction in anogenital distance and retention of nipples in adult male
      rats exposed to finasteride during late gestation. Significant alterations
      induced by exposure to finasteride were mainly in tissues dependent on
      dihydrotestosterone during development.

PMID- 21861714
TI  - Antioxidative mechanisms of whole-apple antioxidants employing different
      varieties from Luxembourg.
AB  - Many health beneficial functions of dietary ingredients, including antimutagenity
      and anticarcinogenity, have been discussed in relation to their antioxidant
      properties. In this study, antioxidative mechanisms of whole-apple antioxidants
      (from seven varieties) were investigated using the 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging capacity assay,
      the ferric-reducing antioxidant power (FRAP) assay, and the ferrous iron(II)
      chelating activity assay. Results indicated the ability of primary antioxidants
      to act as hydrogen or electron donors, with considerable differences depending on
      variety, with ABTS and FRAP values ranging from 270 to 1,142 mg of vitamin C
      equivalents/100 g and from 695 to 3,143 MUmol of Fe/100 g, respectively. However,
      varieties did not display measurable chelating activity except for Florina and
      Graham, exhibiting a weak activity (0.1-0.2 MUg of EDTA equivalents/100 g).
      Correlation analyses showed that polyphenols were major primary antioxidants
      contributing to antioxidative mechanisms (r>0.99, P<.001), whereas their
      involvement as secondary antioxidants (i.e., as chelating compounds) was
      negligible. Our findings further showed that the intake of 100 g of apple fruits
      can provide antioxidants equivalent to approximately 270-1,140 mg of vitamin C,
      with highest antioxidant concentrations for the older varieties Grauapfel and
      Goldparmane.

PMID- 21861715
TI  - Effect of feeding grape pomace on selected metabolic parameters associated with
      high fructose feeding in growing Sprague-Dawley rats.
AB  - The effect of feeding grape pomace on certain metabolic parameters associated
      with high fructose (HF) feeding was studied. Forty male growing Sprague-Dawley
      rats were randomly assigned into groups: (1) control; (2) HF; (3) HF with low
      level (1.5% of diet) grape pomace (HF+LP), and (4) HF with high-level (5.0% of
      diet) grape pomace (HF+HP). The HF+LP and HF+HP diets provided 115 and 218 mg of
      procyanidins/kg, respectively. Compared with the controls, HF-fed animals
      consumed less and were smaller, whereas animals in the HF+LP and HF+HP groups
      were in between. A similar trend was observed for abdominal fat and abdominal fat
      as a percentage of body weight. No change in heart or kidney weight occurred.
      Liver weight as a percentage of body weight was higher for animals when fructose
      was included in the diet compared with those on control diet, and inclusion of
      grape pomace had no effect. Fasting plasma glucose, insulin, and triglyceride
      levels tended to be higher in animals fed HF diet, and grape pomace reduced their
      levels to values similar to the control animals. Compared with control animals,
      HF-fed animals had higher weekly postprandial plasma triglycerides, which were
      reduced by feeding grape pomace, but no change in plasma cholesterol was
      observed. Glucose intolerance was observed in animals fed HF diet and was
      accompanied by a 25% increase in homeostatic model assessment (HOMA) of insulin
      resistance. Inclusion of grape pomace increased glucose tolerance and insulin
      sensitivity. No significant change (P>.1) in HOMA of beta-cell function or
      Quantitative Insulin-Sensitivity Check Index was observed. Overall, HF diet did
      not produce as strong a response of metabolic syndrome as has been shown in the
      literature. The inclusion of grape pomace in the diet was effective in modulating
      some aspects of metabolic parameters associated with metabolic syndrome, and the
      higher level of grape pomace in the diet produced a slightly better response than
      the lower level.

PMID- 21861716
TI  - Chemical and antidiarrheal studies of Plinia cauliflora.
AB  - Plinia cauliflora (Mart.) Kausel, widespread in South America, has edible fruits,
      and its bark is commonly used against diarrhea and other disorders, on account of
      its astringency. Because diarrhea is still one of the most important causes of
      illness and death among children in developing countries, where the population
      turns to traditional medicine for its treatment, the present study determined the
      composition of fruit and leaf extracts of P. cauliflora, analyzed the activity
      against diarrhea by antimicrobial and gastrointestinal motility, and evaluated
      the cytotoxicity of the extracts. Chemical composition was determined by high
      performance liquid chromatograpy-ultraviolet/photodiode array detection.
      Antimicrobial activity was analyzed by agar diffusion and the microdilution
      method against etiological agents of diarrhea. The effect on gastrointestinal
      motility was analyzed using an experimental model in mice. Cytotoxicity was
      evaluated in vitro with the fibroblast cell line SIRC CCL 60, and leaf extract
      showed a 50% inhibitory concentration of 0.48 MUg/mL. Gallic acid, ellagic acid,
      and flavonoid derivatives were detected in the extracts. It was observed that
      fruit and leaf extracts showed some activity against Enterococcus faecalis,
      Escherichia coli, Salmonella sp., and Shigella sp. However, neither extract had
      any effect on gastrointestinal motility.

PMID- 21861717
TI  - Bitter melon extracts in diabetic and normal rats favorably influence blood
      glucose and blood pressure regulation.
AB  - Bitter melon (BM) was tested in normal and streptozotocin (STZ)-induced diabetic
      rats. First, normal and diabetic Wistar rats were given four test extracts (EX-1
      EX-4) of a wild-genotype BM or metformin by intubation. Second, normal Sprague
      Dawley rats were divided into control and three test groups given for 52 days one
      of three BM preparations in food: Chinese or Indian commercial preparations or EX
      4 from experiment I. In experiment I, extracts of BM administered at 50 mg/kg of
      body weight in normal rats reduced blood sugar for 4 hours without, unlike
      metformin, inducing hypoglycemia. In STZ-induced diabetic rats, two extracts
      administered at 250 mg/kg decreased glucose levels to values comparable to
      metformin at 150 mg/kg. At 4 hours, EX-1 and EX-4 significantly reduced blood
      glucose 67% and 63%, respectively, compared with metformin's 54%. In experiment
      II, all test groups had lowered systolic, but not diastolic, blood pressure. The
      China and EX-4 arms had significantly lowered serum glucose levels compared with
      the control. In the glucose tolerance test, only EX-4 had significantly lowered
      glucose levels. Only EX-4 had significantly lowered angiotensin converting enzyme
      (ACE) activity. All active arms showed significance in the losartan challenge
      (the renin-angiotensin system [RAS]), with the greatest effect in the EX-4 group.
      In the N(omega)-nitro-l-arginine-methyl ester challenge, only EX-4 exhibited a
      significant impact on the nitric oxide system, suggesting higher activity in this
      group. In the STZ-induced diabetic rat model, wild-type BM powerfully lowered
      glucose levels, and, in healthy adult rats, wild-type BM exhibited beneficial
      effects in the regulation of blood glucose, in RAS and ACE inhibition, and in
      nitric oxide generation.

PMID- 21861718
TI  - Blueberry intake alters skeletal muscle and adipose tissue peroxisome
      proliferator-activated receptor activity and reduces insulin resistance in obese
      rats.
AB  - Metabolic syndrome can precede the development of type 2 diabetes and
      cardiovascular disease and includes phenotypes such as obesity, systemic
      inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological
      study indicated that blueberry intake reduced cardiovascular mortality in humans,
      but the possible genetic mechanisms of this effect are unknown. Blueberries are a
      rich source of anthocyanins, and anthocyanins can alter the activity of
      peroxisome proliferator-activated receptors (PPARs), which affect energy
      substrate metabolism. The effect of blueberry intake was assessed in obesity
      prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of
      kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole
      highbush blueberry powder or added sugars to match macronutrient and calorie
      content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry
      reduced triglycerides, fasting insulin, homeostasis model index of insulin
      resistance, and glucose area under the curve. Blueberry intake also reduced
      abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and
      affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation.
      In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also
      significantly reduced liver weight, body weight, and total fat mass. Finally,
      Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides,
      but all other measures were unaffected. In conclusion, whole blueberry intake
      reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR
      gene transcripts in adipose and muscle tissue involved in fat and glucose
      metabolism.

PMID- 21861719
TI  - Dietary cinnamon supplementation and changes in systolic blood pressure in
      subjects with type 2 diabetes.
AB  - Experimental and some clinical evidence suggests that ingestion of cinnamon may
      improve metabolic measures in individuals with diabetes; however, few human
      studies have been designed to examine this association as their primary
      objective. In this study adult subjects 30 years of age or older with type 2
      diabetes were randomized to treatment with 1,200 mg/day cinnamon or matched
      placebo. Blood pressure, hemoglobin A1c, fasting blood glucose, lipid profile,
      physical examination, and blood and urine chemistry were measured at baseline and
      at the 12-week follow-up end-of-treatment visit. In total, 59 subjects (40.7%
      female; mean age, 63.05+/-10.85 years) were recruited. Systolic blood pressure
      (SBP) declined from baseline values by 3.4+/-11.4 mm Hg in the cinnamon group and
      increased by 1.9+/-10.2 mm Hg in the placebo group (P=.06). In repeated-measures
      analysis, a significant by-treatment difference over time was detected (P=.02).
      However, when baseline SBP was included in the model as a covariate, change from
      baseline SBP was no longer associated with treatment. Although cinnamon added to
      the diets of spontaneously hypertensive rats has been shown to decrease SBP in a
      dose-dependent manner, results of the present study in humans suggest that the by
      treatment difference in change-from-baseline SBP was a function of regression to
      the mean rather than a treatment-associated change.

PMID- 21861720
TI  - Antioxidant and antimicrobial properties of some lichens and their constituents.
AB  - The aim of this study is to examine the in vitro antioxidant and antimicrobial
      activities of the acetone, methanol, and aqueous extracts of the lichens Cladonia
      furcata (many-forked Cladonia), Hypogymnia physodes (puffed lichen), and
      Umbilicaria polyphylla (manyleaf navel lichen) and the antimicrobial activity of
      fumarprotocetraric acid, gyrophoric acid, and physodic acid isolated from the
      respective lichen species. Antioxidant activity was evaluated by five different
      methods: free radical scavenging, superoxide anion radical scavenging, reducing
      power, determination of total phenolic compounds, and determination of total
      flavonoid content. U. polyphyla exhibited more powerful antioxidant activities
      than the other lichen species examined: methanol extracts of U. polyphyla showed
      90.08% free radical scavenging activities (the ratio was greater than those of
      standard antioxidants). Moreover, the extracts tested had effective reducing
      power and superoxide anion radical scavenging. Total contents of phenol and
      flavonoid in extracts were determined as pyrocatechol equivalents and as rutin
      equivalents, respectively. A significant strong relationship between total
      phenolic and flavonoid contents and their antioxidative activities was observed.
      The antimicrobial activity was estimated by determination of the minimal
      inhibitory concentration by the broth microdilution method against six species of
      bacteria and 10 species of fungi. In general, the lichen extracts tested and
      their respective acids had relatively strong antimicrobial activity against the
      microorganisms tested. The present study shows that the lichen species tested
      demonstrated strong antioxidant and antimicrobial activities. The results suggest
      that lichens may be used as good sources of natural antioxidants and for
      pharmaceutical purposes in treating various diseases.

PMID- 21861721
TI  - Polyphenol content and antioxidant properties of colored soybean seeds from
      central Europe.
AB  - The antioxidant activity and contents of various polyphenol classes in the seeds
      of seven soybean varieties of different seed color and one yellow seed cultivar,
      representing a reference genotype, were evaluated. Total polyphenols and tannins
      were determined after extraction of plant material with 70% aqueous acetone, and
      total flavonoids were extracted with methanol and acetic acid, whereas
      anthocyanins were extracted with 20% aqueous ethanol. In addition, isoflavone
      content and composition were determined using high-performance liquid
      chromatography analysis. Antioxidant activity of seed extracts was evaluated by
      the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity assay. A
      positive linear correlation between antioxidant activity and contents of total
      polyphenols and anthocyanins was established. The highest antioxidant activity
      was observed in the extracts of black and brown varieties, which also showed high
      levels of all polyphenol classes examined. Yellow seed had the highest total
      isoflavone content (3.62 mg/g of dry material). The highest concentration of
      total daidzein was determined in black seeds (>2.0 mg/g of dry material), and the
      highest total glycitein and genistein contents occurred in the yellow cultivar
      (0.53 and 1.49 mg/g of dry material, respectively). According to our results,
      varieties of black and brown seeds could be of special interest not only for
      their large content of total polyphenols, ranging from 4.94 to 6.22 mg of gallic
      acid equivalents/g of dry material, but also for their high content of natural
      antioxidants such as anthocyanins.

PMID- 21861722
TI  - Anti-obesity and antioxidative effects of purple sweet potato extract in 3T3-L1
      adipocytes in vitro.
AB  - The purpose of the current study was to determine the anti-obesity and anti
      inflammatory effects of an extract of purple sweet potatoes (PSPs) on 3T3-L1
      adipocytes. For this purpose, differentiated 3T3-L1 adipocytes were treated with
      a PSP extract at concentrations of 1,000, 2,000, and 3,000 MUg/mL for 24 hours.
      Then, we measured the changes in the sizes of the adipocytes, the secretion of
      leptin, and the mRNA/protein expression of lipogenic, inflammatory, and lipolytic
      factors after the treatment with the PSP extract. The PSP extract diminished
      leptin secretion, indicating that growth of fat droplets was suppressed. The
      extract also suppressed the expression of mRNAs of lipogenic and inflammatory
      factors and promoted lipolytic action. The antioxidative activity of the PSP
      extract was also measured using three different in vitro methods: 1,1-diphenyl-2
      picrylhydrazyl free radical scavenging activity, ferric reducing ability
      potential assay, and chelating activity of transition metal ions. Taken together,
      our study shows that PSP extract has antilipogenic, anti-inflammatory, and
      lipolytic effects on adipocytes and has radical scavenging and reducing activity.

PMID- 21861723
TI  - Leaf extract of Moringa oleifera prevents ionizing radiation-induced oxidative
      stress in mice.
AB  - The present study evaluated the hepatoprotective effect of aqueous ethanolic
      Moringa oleifera leaf extract (MoLE) against radiation-induced oxidative stress,
      which is assessed in terms of inflammation and lipid peroxidation. Swiss albino
      mice were administered MoLE (300 mg/kg of body weight) for 15 consecutive days
      before exposing them to a single dose of 5 Gy of 60Co gamma-irradiation. Mice
      were sacrificed at 4 hours after irradiation. Liver was collected for
      immunoblotting and biochemical tests for the detection of markers of hepatic
      oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-kappaB) and
      lipid peroxidation were augmented, whereas the superoxide dismutase (SOD),
      catalase (CAT), reduced glutathione (GSH), and ferric reducing antioxidant power
      (FRAP) values were decreased by radiation exposure. Translocation of NF-kappaB
      from cytoplasm to nucleus and lipid peroxidation were found to be inhibited,
      whereas increases in SOD, CAT, GSH, and FRAP were observed in the mice treated
      with MoLE prior to irradiation. Therefore pretreatment with MoLE protected
      against gamma-radiation-induced liver damage. The protection may be attributed to
      the free radical scavenging activity of MoLE, through which it can ameliorate
      radiation-induced oxidative stress.

PMID- 21861724
TI  - The potential of fenugreek (Trigonella foenum-graecum) as a functional food and
      nutraceutical and its effects on glycemia and lipidemia.
AB  - Dietary fiber from fenugreek blunts glucose and cholesterol after a meal and
      regulates the production of cholesterol in the liver. The mechanisms for these
      effects have not been fully elucidated. Fenugreek seeds contain 45.4% dietary
      fiber (32% insoluble and 13.3% soluble), and the gum is composed of galactose and
      mannose. The latter compounds are associated with reduced glycemia and
      cholesterolemia. Fenugreek's hypoglycemic effect has been especially documented
      in humans and animals with type 1 and type 2 diabetes mellitus. In addition, this
      dietary fiber has potential for widespread use in the food industry because its
      galactomannan composition has emulsifying and stabilizing properties. Flour
      supplemented with 8%-10% fenugreek dietary fiber has been used in the production
      of baked goods such as bread, pizza, muffins, and cakes. This application to
      flour allows for the production of functional foods that may be widely acceptable
      to consumers observing western diets.

PMID- 21861725
TI  - The effect of stinging nettle (Urtica dioica) seed oil on experimental colitis in
      rats.
AB  - This study investigated the effect of Urtica dioica, known as stinging nettle,
      seed oil (UDO) treatment on colonic tissue and blood parameters of
      trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental
      colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic
      administration with a 8-cm-long cannula with rats under ether anesthesia,
      assigned to a colitis group and a colitis+UDO group. Rats in the control group
      were given saline at the same volume by intracolonic administration. UDO (2.5
      mL/kg) was given to the colitis+UDO group by oral administration throughout a 3
      day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was
      given to the control and colitis groups at the same volume by oral
      administration. At the end of the experiment macroscopic lesions were scored, and
      the degree of oxidant damage was evaluated by colonic total protein, sialic acid,
      malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor
      activity, and superoxide dismutase and myeloperoxidase activities. Colonic
      tissues were also examined by histological and cytological analysis. Pro
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol
      levels were analyzed in blood samples. We found that UDO decreased levels of pro
      inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol,
      which were increased in colitis. UDO administration ameliorated the TNBS-induced
      disturbances in colonic tissue except for MDA. In conclusion, UDO, through its
      anti-inflammatory and antioxidant actions, merits consideration as a potential
      agent in ameliorating colonic inflammation.

PMID- 21861726
TI  - The antioxidant potency of Punica granatum L. Fruit peel reduces cell
      proliferation and induces apoptosis on breast cancer.
AB  - Pomegranate (Punica granatum L.) is known to possess pharmacological activities,
      such as antioxidant and anticancer. In this study, we evaluated the antioxidant
      potency of a methanolic pomegranate fruit peel extract (PPE) and the relation
      with its antiproliferative and apoptotic effects on MCF-7 human breast cancer
      cells. Total phenolic content and antioxidant activity of PPE were determined
      using the Folin-Ciocalteau and the 2,2-diphenyl-l-picrylhydrazyl free radical
      methods, respectively. Phenolic acids present in the extract were characterized
      by a reverse-phase high-performance liquid chromatography (HPLC) method. Cell
      proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide reduction assay. The apoptotic effects were
      determined by in situ Tdt-mediated dUTP nick end-labeling assay, and Bax/Bcl-2
      mRNA expression levels were measured by reverse transcription-polymerase chain
      reaction. The extraction yield as a percentage of plant material was 37.97%
      (wt/wt), and total phenolic content was 331.28 mg of gallic acid equivalents/g of
      extract. According to HPLC analysis, the most abundant phenolic acid detected in
      the extract was ellagic acid. MCF-7 cell proliferation decreased depending on PPE
      concentration (25, 50, 100, 200, and 300 MUg/mL) and incubation times (24, 48,
      and 72 hours). After 48 and 72 hours, the apoptotic cell numbers were
      significantly increased at 100, 200, and 300 MUg/mL PPE concentrations. In
      addition, expression of the pro-apoptotic gene Bax was increased, and that of the
      anti-apoptotic gene Bcl-2 was decreased after 200 and 300 MUg/mL PPE treatment
      for 48 and 72 hours. Because PPE reduced cell proliferation and induced apoptosis
      on MCF-7 cancer cells, we believe that PPE has important antioxidant and
      apoptotic effects.

PMID- 21861727
TI  - Biochemical characteristics and biological properties of Annurca apple cider.
AB  - Our work aimed to investigate the phenolic composition and antioxidant capacity
      of the de-alcoholized extract of cider obtained from the Annurca apple (Malus
      domestica var. Annurca). The antimicrobial effect of the extract against
      different pathogens, including Chronobacter sakazakii, was also examined. The
      extract's potential anti-quorum-sensing (AQS) activity was assessed using the
      test microorganism Chromobacterium violaceum. Biochemical analysis of the extract
      using ultra-performance liquid chromatography revealed catechin and caffeic acid
      as the most abundant polyphenols present, which represented about 35.5% and 36.6%
      of the total phenolics identified, respectively. An antioxidant capacity was also
      found (50% effective concentraiton=10 MUL). The extract exhibited clear
      antimicrobial activity against all strains used in the experiments. Escherichia
      coli and Bacillus cereus were the most sensitive bacteria to the antimicrobial
      activity. The extract also inhibited the growth of the emergent pathogen strain
      C. sakazakii. The AQS activity of apple cider is reported here for the first
      time. In conclusion, our results demonstrate some biological properties of the
      apple cider and contribute to reinforcing the potential of the apple and its
      derivatives as functional components of the diet.

PMID- 21861728
TI  - Antiglycation and antioxidant properties of soy sauces.
AB  - Diabetes-induced hyperglycemia increases formation of advanced glycation end
      products (AGEs) and metal-catalyzed production of free radicals. This study
      compared the antioxidant capacities of dark and light soy sauces of different
      brands and investigated their abilities to inhibit AGEs and whether their
      mechanism of action was pre- or post-Amadori or involved chelation of transition
      metals. The antioxidant capacities of soy sauces were compared using the 2,2'
      azinobis(3-ethylbenzothiazoline-6-sulfonate) method and by measuring their total
      phenolic contents. Model proteins (lysozyme, albumin) were glycated using
      fructose with or without soy sauces with subsequent analysis of cross-linked AGEs
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The effect of soy
      sauces on pre- and post-Amadori inhibition of AGEs was investigated by measuring
      fructosamine and AGEs following reincubation of ribose-glycated (ribated)
      lysozyme, respectively. Dark soy sauces had higher antioxidant capacities and
      phenolic content and were more effective inhibitors of post-Amadori-derived cross
      linked AGEs. However, light soy sauces were more effective at inhibiting
      fructosamine and had more potent metal chelation properties. This study reports
      the antiglycation properties of soy sauces, but further studies are required to
      determine the constituents responsible for this effect and whether soy sauce
      consumption can reduce oxidative stress and AGEs in diabetic subjects.

PMID- 21861729
TI  - A meta-analysis of outcome after percutaneous endovascular aortic aneurysm repair
      using different size sheaths or endograft delivery systems.
AB  - PURPOSE: To determine via a meta-analysis if the success rates for percutaneous
      EVAR using the "preclose" technique with suture-mediated vascular closure devices
      (SMCDs) are higher for smaller sheaths [<= 18-F outer diameter (OD)] than for
      larger sheaths (>=20-F). METHODS: All English-language studies on percutaneous
      EVAR outcomes related to sheath sizes published between 1999 and August 30, 2010,
      were searched using MEDLINE and SCOPUS. Randomized trials, retrospective or
      prospective observational studies, and original articles (including a review)
      were included. The search identified 32 relevant full-text studies; data on
      percutaneous EVAR outcomes per sheath size category (<= 18-F and >= 20-F OD) were
      included in the final meta-analysis of data from 17 studies (1 randomized
      controlled trial and 8 retrospective and 8 prospective cohort observational
      studies). The final analysis included 1440 patients and 2447 femoral access
      sites. Primary success was defined as closure of a common femoral artery
      arteriotomy without the need for any adjunctive surgical or endovascular
      procedure. RESULTS: Pooled data revealed that success rates were significantly
      better when percutaneous EVAR was performed with <= 18-F sheaths than with >= 20
      F sheaths (odds ratio 1.78, 95% confidence interval 1.24 to 2.54, p = 0.002).
      This benefit, although not significant, was more pronounced when multiple rather
      than single pre-applied SMCDs were deployed (odds ratio 2.16 vs. 1.64,
      respectively; p = 0.353). CONCLUSION: When considering primary success, it
      appears that larger-bore femoral access sheaths (>= 20-F) introduced for
      percutaneous EVAR after pre-application of SMCDs are predictors of primary
      failure and the need for conversion to a femoral cutdown. More advanced large
      bore SMCDs are required to further reduce the necessity for conversion. Planned
      use of multiple SMCDs might be more beneficial when <= 18-F sheaths are required.

PMID- 21861730
TI  - Commentary: Percutaneous access for endovascular aortic surgery: the way forward.

PMID- 21861731
TI  - Endograft accommodation on the aortic bifurcation: an overview of anatomical
      fixation and implications for long-term stent-graft stability.
AB  - In light of the results of randomized trials, it seems that despite the favorable
      short and midterm outcomes of standard endografts, concern over endograft
      migration has escalated, as this event will be responsible for almost all late
      complications in endovascular aneurysm repair (EVAR). Migration forces, both
      caudal and sideways, depend heavily on blood pressure, inlet diameter, and
      angulation of the stent-graft, while the bifurcation generates more force than
      any other segment of the stent-graft. It thus seems that the position of the
      endograft's flow divider influences force distribution and migration risk.
      Additionally, due to concomitant ongoing aortic degeneration, postoperative
      dilatation of the infrarenal aortic neck poses a threat to EVAR patients as soon
      as the diameter of the infrarenal neck reaches the dimensions of the proximal
      graft. This review evaluates the significance of endograft accommodation on the
      aortic bifurcation and cumulative experience of the only endografts utilizing
      this feature: the Zenith Composite and the Powerlink.

PMID- 21861732
TI  - Branched grafts for thoracoabdominal aneurysms: off-label use of FDA-approved
      devices.
AB  - PURPOSE: To report off-label use of approved off-the-shelf endografts with no
      modification to the devices for the management of thoracoabdominal aneurysms
      (TAAA). TECHNIQUE: The parallel endograft octopus technique is demonstrated in a
      68-year-old woman with a past history of open TAAA repair with a patch reimplant
      of the visceral vessels who now presented with back pain. Non-contrast computed
      tomography revealed a 6.8-cm aneurysm of the visceral segment involving the
      celiac trunk, superior mesenteric artery (SMA), and right renal artery. As she
      was at high risk for redo surgery due to significant pulmonary dysfunction, she
      was an ideal candidate for a branched graft, but she could not travel to an
      investigational site for a custom graft. At surgery, 4 sheaths were introduced, 2
      retrograde (18-F DrySeal) and 2 (8-F) antegrade, via the femoral arteries. The 18
      F sheaths on both sides were connected to the 8-F sheaths for continued limb
      perfusion. Via an axillary conduit, a 12-F, 80-cm sheath was introduced into the
      proximal thoracic aorta over a stiff wire. Subsequently, two 28-mm Excluder
      endografts were introduced via the bilateral 18-F femoral sheaths and positioned
      side by side in the descending thoracic aorta such that the lower end of the
      Excluder limbs were positioned >=2 cm above the target visceral vessels. Viabahn
      stent-grafts were then deployed in the celiac axis, SMA, and right renal artery
      from the axillary conduit. Subsequently, a 23-mm Excluder was deployed within the
      distal end of the upsized limb and extended to both common iliac arteries.
      Imaging at 6 months demonstrated no endoleaks, with good flow to all visceral
      vessels. CONCLUSION: The parallel endograft octopus technique described here,
      which has been applied successfully in 9 cases thus far, is a relatively simple
      method using currently available devices with no requirement for device
      modification or customization. Although this technique shows promise, long-term
      data will be required to prove efficacy. This technique demonstrates a concept
      for future development of branched graft technology.

PMID- 21861733
TI  - Early results of left carotid chimney technique in endovascular repair of acute
      non-a-non-B aortic dissections.
AB  - PURPOSE: To report our early experience with endovascular repair of acute non-A
      non-B aortic dissections using chimney grafts to preserve blood flow to a left
      common carotid artery (LCCA) located in the proximal landing zone. METHODS: From
      June 2009 to May 2010, 8 patients (7 men; mean age 49 years, range 29-75) with
      acute non-A-non-B aortic dissection and no adequate proximal sealing zones
      underwent thoracic endovascular aortic repair (TEVAR). Covered stents were placed
      parallel to the aortic stent-grafts to restore flow to the LCCAs while extending
      the proximal fixation zones; the left subclavian arteries were intentionally
      covered after carefully cerebrovascular assessment. Follow-up examinations
      included computed tomography (CT) at 2 weeks, 3 months, 6 months, 12 months, and
      yearly thereafter. RESULTS: All the procedures were completed successfully, with
      one main aortic stent-graft deployed and one chimney graft implanted in the LCCA.
      Two retrograde type II endoleaks identified intraoperatively were left untreated
      but followed closely using CT. There were no instances of puncture site
      complications, stroke, paralysis, or death during the hospital stay. The 30-day
      mortality was 0%. During the mean 11.4-month follow-up (range 6-15), there was no
      mortality, and duplex ultrasound and CT showed patency of all stent-grafts,
      enlargement of the true lumen, and compression of the false lumen. One type II
      endoleak disappeared in 2 weeks postoperatively, while the other gradually faded
      until it was nearly gone at 11 months postoperatively. During follow-up, no renal
      insufficiency, new late endoleaks, endograft migration, fracture, stent-graft
      related complications, or deaths were observed. CONCLUSION: In short-term follow
      up, TEVAR combined with the chimney technique seems promising for aortic
      dissections that involve the aortic arch with inadequate proximal sealing zones.
      More cases and long-term results are needed to evaluate the safety and efficiency
      of this alternative endovascular technique.

PMID- 21861734
TI  - Impact of stent-graft development on outcome of endovascular repair of acute
      traumatic transection of the thoracic aorta.
AB  - PURPOSE: To analyze the impact of stent-graft design on the outcome of
      endovascular repair of acute traumatic thoracic aortic transection. METHODS:
      Forty-eight patients (38 men; mean age 37 +/- 11 years) underwent endovascular
      repair for an acute traumatic aortic rupture between April 2001 and March 2011.
      Up to October 2007, 32 patients (mean age 41 +/- 16 years; group 1) were treated
      with the first generation of commercially available thoracic stent-grafts (10
      Talent, 20 Excluder/TAG, 2 Zenith). From November 2007, 16 patients (mean age 42
      +/- 19 years; group 2) were treated with second-generation thoracic stent-grafts
      (13 Valiant and 3 C-TAG). The 2 groups were statistically comparable. Follow-up
      computed tomography was performed at 1 week; at 3 and 6 months; and annually
      thereafter. RESULTS: In the 2 groups, the mortality rate related to aortic repair
      was nil. All the patients have completed each of their scheduled follow-up
      evaluations and CT scans. The morbidity rate was significantly reduced (p =
      0.0003) from 18.7% (first generation) to 6.2% (second generation). Type I
      endoleak (n = 1), inadvertent coverage of the supra-aortic trunks (n = 3), and
      stent-graft collapse (n = 2) occurred only with the first-generation stent
      grafts. One iliac artery rupture occurred with a second-generation stent-graft.
      CONCLUSION: Enhanced stent-graft conformability and more accurate delivery
      systems have significantly decreased the morbidity of endovascular repair of
      acute traumatic transection of the thoracic aorta. The increasing clinical
      experience may also have contributed to improved results.

PMID- 21861735
TI  - Thoracic aortic pulsatility decreases during hypovolemic shock: implications for
      stent-graft sizing.
AB  - PURPOSE: To investigate the thoracic aortic pulsatility during hypovolemic shock
      in an experimental porcine model. METHODS: The circulating blood volume of 7
      healthy Yorkshire pigs was gradually lowered until the subjects had lost 40% of
      their normal blood volume. Intravascular ultrasound was used to assess the aortic
      pulsatility in normovolemic and hypovolemic state at the level of the ascending
      and descending thoracic aorta. RESULTS: The mean aortic pulsatility at the level
      of the ascending aorta decreased from 15.9% +/- 7.2% (range 6.3%-25.7%) in
      normovolemia to 6.2% +/- 2.8% (range 2.9%-10.7%, p = 0.018) in hypovolemia. At
      the level of the descending thoracic aorta, the mean aortic pulsatility decreased
      from 8.7% +/- 2.8% (range 4.4%-12.2%) at baseline to 5.6% +/- 2.5% (range 1.5%
      9.5%, p = 0.028) in hypovolemia. The maximum mean aortic diameter, obtained in
      cardiac systole, was significantly smaller as well at both evaluated levels
      during hypovolemic shock compared with the mean diameter in normovolemia.
      CONCLUSION: The thoracic aortic diameter and pulsatility decreased significantly
      during hypovolemic shock in this porcine model, most impressively at the level of
      the ascending aorta. Electrocardiographically-gated imaging may not be necessary
      for hypovolemic patients with acute aortic disease requiring endovascular repair
      because of the minimal aortic pulsatility.

PMID- 21861736
TI  - Aortic hammer syndrome.
AB  - PURPOSE: To present a case of penetrating aortic ulcer with extraordinary
      etiology. CASE REPORT: A 57-year-old man was admitted with acute retrosternal and
      interscapular pain. He was a demolition worker and often used a pneumatic drill
      to which he pressed his chest as he drilled. Clinical examination showed
      previously undiagnosed hypertension. Computed tomographic angiography disclosed a
      penetrating aortic ulcer in the descending thoracic aorta without any sign of
      atherosclerosis. Initial treatment consisted of blood pressure control. However,
      due to progression of the lesion, endovascular treatment was performed to implant
      a covered endoprosthesis. CONCLUSION: We hypothesize that the etiology of the
      ulcer was the shear forces developed by incorrect, repetitive use of the
      pneumatic hammer in combination with the untreated hypertension. This is
      analogous to the hypothenar hammer syndrome, and we propose naming this the
      "aortic hammer syndrome."

PMID- 21861737
TI  - Commentary: The so-called "aortic hammer syndrome".

PMID- 21861738
TI  - Retrograde popliteal access in the supine patient for recanalization of the
      superficial femoral artery: initial results.
AB  - PURPOSE: To report an initial experience of superficial femoral artery (SFA)
      recanalization performed with a dual femoral-popliteal approach in the supine
      patient. METHODS: From May 2008 to April 2010, 26 patients (16 men; mean age 68
      +/- 6.3 years) with intermittent claudication and chronic SFA occlusion (mean
      length 97.4 +/- 3.8 mm, range 35-220) underwent percutaneous recanalization from
      a retrograde popliteal access. The common femoral artery was punctured with an
      antegrade (n = 9) or retrograde contralateral (n = 17) approach, then with the
      patient still supine and the knee gently flexed and medially rotated, the
      popliteal artery was punctured using an 18-G needle under ultrasound (10, 38.4%)
      or fluoroscopic (16, 61.5%) guidance with a roadmap technique. Once the SFA was
      recanalized, the procedure was completed with angioplasty and stenting from the
      femoral approach. At the end of the procedure, hemostasis at the popliteal access
      was obtained with manual compression (5-10 minutes). RESULTS: Technical success
      (puncture of the popliteal artery and SFA recanalization) was achieved in all
      cases. In the majority of patients (24, 91.6%), endoluminal recanalization was
      possible from the popliteal access; SFA recanalization in the other 2 cases was
      obtained through the subintimal space. Two small hematomas were found in the
      popliteal region, but no pseudoaneurysm or arteriovenous fistulas were seen on
      duplex examinations during a mean 12.5-month follow-up (range 6-28). Twenty
      (76.9%) SFAs were patent; in-stent restenosis occurred in the remaining 6 (23%).
      Primary patency was 80.7% at 6 months and 76.9% at 1 year. No stent fracture was
      observed. CONCLUSION: The retrograde popliteal approach with the patient in the
      supine position can be considered a "first choice" method for safe and effective
      SFA recanalization, especially in occlusions located at the distal and mid
      portion SFA.

PMID- 21861739
TI  - Commentary: Miniaturized retrograde popliteal approach in a supine patient.

PMID- 21861740
TI  - Determinants and outcomes of asystole during carotid artery stenting.
AB  - PURPOSE: To examine the predictors and outcomes of asystole in patients who
      undergo carotid artery stenting (CAS). METHODS: Forty-three patients (24 men;
      median age 69 years) with asystole were identified after reviewing the case
      records of 884 patients who underwent CAS at our institution between 1997 and
      2009. The control group comprised 678 patients who underwent stenting in the
      carotid sinus area without asystole. Univariate and multivariate logistic
      analyses were used to determine the predictors and outcomes of asystole. RESULTS:
      A right-sided procedure was more likely to result in asystole [odds ratio (OR)
      11.4, 95% CI 4.0 to 32.7, p<0.0001] compared with a left-sided procedure.
      Patients with a contralateral carotid stenosis (OR 1.7, 95% CI 1.0 to 2.8, p =
      0.04) and a left ventricular ejection fraction (LVEF) of <40% (OR 2.2, 95% CI 1.1
      to 4.5, p = 0.03) were also more likely to suffer asystole. Smokers appeared less
      likely to develop asystole (OR 0.25, 95% CI 0.12 to 0.56, p = 0.0006).
      Periprocedural stroke (14% vs. 1.3%, p<0.001), length of stay during index
      hospitalization (2.2 vs. 1.2 days, p = 0.002), and 30-day mortality (11.6% vs.
      4.1%, p = 0.02) were significantly higher in the asystole group. CONCLUSION:
      Asystole during CAS is more likely to occur in patients undergoing procedures in
      the right carotid sinus area, in those who have significant contralateral carotid
      stenosis, and in those with a reduced LVEF. More caution should be exercised
      during right-sided than left-sided CAS procedures.

PMID- 21861741
TI  - Interpretation of TCD spectral patterns detected during carotid artery stent
      interventions.
AB  - PURPOSE: To classify transcranial Doppler (TCD) spectral patterns and analyze the
      significance of the patterns in the determination of hemodynamic alterations
      occurring during filter-protected carotid artery stent (CAS) procedures. METHODS:
      Data on middle cerebral artery (MCA) monitoring and post-CAS diffusion weighted
      magnetic resonance imaging (DWMRI) were reviewed for 53 patients (45 men; mean
      age 67.6 +/- 8.3 years) who underwent TCD evaluation before CAS and TCD
      monitoring during the procedure. TCD spectral patterns were classified according
      to the hemodynamic changes that occurred after different portions of the CAS
      procedures. The relationships among the spectral patterns and the frequency and
      location of new DWMRI lesions were analyzed. RESULTS: TCD spectral changes were
      classified into 4 patterns: (1) microemboli signals (53, 100%), (2) right-left
      collateral signals (31/53, 58%), (3) spectral suppression after balloon inflation
      (31/44, 70%), and (4) continuous spectral suppression after balloon removal
      (4/44, 9%). Even though microembolic signals were frequently observed during CAS,
      the new DWMRI lesions were more frequently observed outside of the cerebral
      territory (78%) rather than in the territory ipsilateral to CAS (47%). The
      presence of right-left collaterals was related to less severe balloon-related
      spectral suppression on ipsilateral MCA (p<0.05). Continuous spectral suppression
      appeared after stent deployment and balloon dilation and was immediately reversed
      after removal of the filter device. CONCLUSION: The spectral patterns classified
      in the present study may prove useful in anticipating CAS procedure-related
      hemodynamic alterations. Close hemodynamic observation using these spectral
      patterns could be helpful in preventing serious complications during CAS.

PMID- 21861742
TI  - Commentary: Carotid artery stenting drawbacks: microembolic ischemic cerebral
      lesions--do they matter?

PMID- 21861743
TI  - An endovascular procedure-specific neurological examination scheme for
      intraprocedural monitoring in awake patients.
AB  - PURPOSE: To describe a new neurological examination scheme (NES) adapted to the
      unique environment of neuroendovascular procedures. METHODS: The endovascular
      procedure-specific (NES) evaluates 6 aspects of neurological function, including
      language, gaze deviation, visual fields, cranial nerves, and the function of the
      upper lower extremities (left and right). To evaluate this protocol, the results
      of neurological examinations based on the NES were compared to the concurrently
      assessed National Institutes of Health Stroke Scale (NIHSS) scores in 20 patients
      (11 men; mean age 47 +/- 18 years) during neuroendovascular procedures. All
      examinations were performed by qualified vascular neurologists certified for
      NIHSS score ascertainment in awake patients undergoing any neuroendovascular
      procedures. The positive predictive value and Spearman rank correlation
      coefficient were determined to assess the relationship between the 2 scores in
      the study sample. RESULTS: The positive predictive value of endovascular
      procedure-specific NES compared with the NIHSS score was 100%. The deficits most
      frequently detected by the endovascular procedure-specific NES were in the
      cranial nerves and upper and/or lower extremity strength items. Overall, the
      Spearman rank correlation coefficient was 0.96 (p<0.001) between both methods. In
      a subset analysis of patients with deficits detected by NIHSS, the correlation
      coefficient between the 2 methods was 0.95 (p<0.001). CONCLUSION: No standard
      method has been developed for examining the neurological status of the awake
      patient under the unique intraprocedural circumstances that surround
      neuroendovascular procedures. The NES detected neurological deficits with a high
      level of agreement to the more detailed NIHSS assessment, which supports further
      evaluation of the NES.

PMID- 21861744
TI  - Commentary: The endovascular procedure-specific neurological examination scheme.

PMID- 21861745
TI  - A case of contrast-induced encephalopathy using iodixanol.
AB  - PURPOSE: To document a heretofore unreported complication of the contrast agent
      iodixanol during an endovascular procedure. CASE REPORT: A 76-year-old woman with
      a history of coronary artery disease was admitted to the emergency department for
      recurrent transient ischemic attacks. Before combined percutaneous transluminal
      coronary angioplasty and carotid artery stenting (CAS) using iodixanol, the
      patient suffered from concomitant unstable angina and recurrent transient
      ischemic attacks. The total amount of iodixanol used during the CAS procedure was
      300 mL. Contrast-induced encephalopathy, which manifested as aphasia, stupor, and
      full hemiparesis immediately after the combined procedure, was diagnosed by
      urgent computed tomography. Treatment was based on anti-edema drugs, and the
      patient made a complete recovery within 48 hours, without any neurological
      sequelae. CONCLUSION: Although previously reported in relation to other types of
      contrast media, contrast-induced encephalopathy has never been described as a
      complication of an endovascular procedure using iodixanol.

PMID- 21861746
TI  - Commentary: New insights into the risk factors of contrast-induced
      encephalopathy.

PMID- 21861747
TI  - Comparison of short- and long-term results of drug-eluting vs. bare metal
      stenting in the porcine internal carotid artery.
AB  - PURPOSE: To evaluate the development of neointimal hyperplasia after implantation
      of drug-eluting stents (paclitaxel) compared to bare metal stents in porcine
      internal carotid arteries (ICAs). METHODS: While drug-eluting stents have
      effectively reduced neointimal proliferation in porcine external carotid
      arteries, the porcine internal carotid artery (ICA) is more sensitive to shear
      stress and altered flow conditions. Thus, a study was conducted to evaluate bare
      vs. drug-eluting stents in porcine ICAs. Under general anesthesia, 18 domestic
      pigs were implanted with paclitaxel-eluting (n = 18) and bare (n = 18) stents in
      the left and right ICAs, respectively. After 1 and 3 months, control carotid
      angiography was performed, followed by histopathological and histomorphometric
      analyses of the stented ICA. RESULTS: Histopathological results (fibrin
      deposition, necrosis, inflammation) were similar in the groups at 1 and 3 months.
      Moreover, the injury score and rate of endothelialization did not differ between
      the groups. Histomorphometric analysis after 1 month revealed significantly
      (p<0.05) less neointimal hyperplasia after implantation of paclitaxel-eluting
      stents. The antiproliferative effect of paclitaxel-eluting stents were maintained
      during the 3-month follow-up: the neointimal area was 0.7 +/- 0.5 vs. 1.2 +/- 0.6
      mm(2) (p<0.01), the area stenosis was 23.5% +/- 13.9% vs. 37.8% +/- 14.4%
      (p<0.01), the maximal neointimal thickness was 0.2 +/- 0.1 vs. 0.2 +/- 0.9 mm
      (p<0.05) in paclitaxel-eluting vs. bare stents, respectively. Implantation of
      paclitaxel-eluting and bare stents did not lead to edge restenosis or vessel
      remodeling in porcine ICAs at 1 or 3 months. CONCLUSION: Compared to bare metal
      stents, drug-eluting stents implanted in the porcine ICA produced significantly
      less neointimal hyperplasia.

PMID- 21861748
TI  - Computational analysis of stresses acting on intermodular junctions in thoracic
      aortic endografts.
AB  - PURPOSE: To evaluate the biomechanical and hemodynamic forces acting on the
      intermodular junctions of a multi-component thoracic endograft and elucidate
      their influence on the development of type III endoleak due to disconnection of
      stent-graft segments. METHODS: Three-dimensional computer models of the thoracic
      aorta and a 4-component thoracic endograft were constructed using postoperative
      (baseline) and follow-up computed tomography (CT) data from a 69-year-old patient
      who developed type III endoleak 4 years after stent-graft placement.
      Computational fluid dynamics (CFD) techniques were used to quantitate the
      displacement forces acting on the device. The contact stresses between the
      different modules of the graft were then quantified using computational solid
      mechanics (CSM) techniques. Lastly, the intermodular junction frictional
      stability was evaluated using a Coulomb model. RESULTS: The CFD analysis revealed
      that curvature and length are key determinants of the displacement forces
      experienced by each endograft and that the first 2 modules were exposed to
      displacement forces acting in opposite directions in both the lateral and
      longitudinal axes. The CSM analysis revealed that the highest concentration of
      stresses occurred at the junction between the first and second modules of the
      device. Furthermore, the frictional analysis demonstrated that most of the
      surface area (53%) of this junction had unstable contact. The predicted critical
      zone of intermodular stress concentration and frictional instability matched the
      location of the type III endoleak observed in the 4-year follow-up CT image.
      CONCLUSION: The region of larger intermodular stresses and highest frictional
      instability correlated with the zone where a type III endoleak developed 4 years
      after thoracic stent-graft placement. Computational techniques can be helpful in
      evaluating the risk of endograft migration and potential for modular
      disconnection and may be useful in improving device placement strategies and
      endograft design.

PMID- 21861749
TI  - Magnitude of the forces acting on target vessel stents as a result of a mismatch
      between native aortic anatomy and fenestrated stent-grafts.
AB  - PURPOSE: To quantify the compression force acting on target vessel stents as a
      consequence of the misalignment between the native aortic anatomy and the
      fenestrated stent-graft owing to measuring errors during the design of the
      device. METHODS: The material properties of a fenestrated Zenith stent-graft were
      determined using a standardized tensile testing protocol. Aortic anatomy was
      modeled using fresh porcine aortas that were subjected to tensile testing. The
      net force acting on a target vessel stent due to incremental discrepancy between
      the target vessel ostia and the stent-graft fenestrations was calculated as the
      difference in wall tension between the aorta and the stent-graft in diastole and
      systole. The change in diameter between diastole and systole was set to 8%.
      RESULTS: Using the diastole model, underestimation of circumferential target
      vessel position by 15 degrees , 22.5 degrees , and 30 degrees  resulted in net
      forces on the target vessel stent of 0.6, 0.8, and 1.1 N, respectively.
      Overestimation of target vessel position by the same increments resulted in net
      forces of 0.3, 0.6, and 0.9 N, respectively. With the systolic model,
      underestimating target vessel position by 30 degrees  resulted in a 2.1-N maximum
      force on the stent, which potentially threatened the seal. In the longitudinal
      direction, underestimating target vessel separation by up to 10 mm resulted in a
      maximal force on the stent of 6.1 N, while overestimating target vessel
      separation did not result in any additional force on the stent due to fabric
      infolding. CONCLUSION: The magnitude of the forces generated solely due to
      mismatch between stent-graft design and native anatomy is modest and is unlikely
      to cause significant deformation of target vessel stents. Mismatch, however, may
      cause loss of seal.

PMID- 21861750
TI  - Impact of stent-graft oversizing on the thoracic aorta: experimental study in a
      porcine model.
AB  - PURPOSE: To analyze in an experimental animal model the effect of 4 different
      levels of stents-graft oversizing on non-atherosclerotic aortas such as those
      found in young individuals who undergo stent-graft repair for traumatic aortic
      injuries. METHODS: The diameter of the porcine thoracic aorta is similar to the
      aorta of young adults (18-20 mm), so 25 pigs were randomized into 5 groups: 1
      control (without stent-graft) and 4 oversizing groups (A: 10%-19%, B: 20%-29%, C:
      30%-39%, and D: >40%). Two types of biomechanical tests were performed on all
      aortas 4 weeks after endoprosthesis deployment. RESULTS: The results of the
      detachment test, which analyzed the strength necessary to remove the stent-graft
      from the aorta, were similar in the 4 groups (A: 42 N, B: 41 N, C: 46 N, and D:
      46 N). However, 2 aortas ruptured during the tests (groups C and D). The second
      test was performed in 3 aortic segments. Maximum shear strength, maximum stress,
      and maximum tension supported by the aortic wall had a negative and linear
      correlation with oversizing. There were significant differences in all 4 groups
      when compared with the control group. Strain, which reflects the elastic
      properties of the aortic wall, was very similar in all 4 groups, but a great
      difference was found when compared with the control group (p<0.0001). CONCLUSION:
      The study showed an important subacute change in the biomechanical properties of
      the aortic wall after implantation of an oversized endoprosthesis. This weakness
      of the aortic wall was confirmed by 2 ruptures during the detachment test. These
      results partially explain the interaction of stent-grafts with non
      atherosclerotic thoracic aortas and may serve as a basis for further studies and
      the development of specific material to be used in vascular trauma and young
      patients.

PMID- 21861751
TI  - Adjunctive stenting of endograft limbs during endovascular treatment of
      infrarenal aortic and iliac aneurysms according to 3-projection completion
      angiography.
AB  - PURPOSE: To evaluate the role of 3-projection completion angiography in defining
      endograft limb stenosis after endovascular aneurysm repair (EVAR) and to
      determine the role of adjunctive stenting in reducing the risk of endograft limb
      occlusion. METHODS: In our center, stent-graft limb dilation was routinely done
      after endograft deployment in patients with preoperatively identified severe
      iliac axis angulation to reduce the incidence of limb stenosis. Completion
      angiography was then routinely performed in anteroposterior (AP) and 45 degrees 
      right and left oblique projections to identify perioperative endograft limb
      stenosis after the stiff guidewires were removed. Adjunctive stenting was used in
      iliac limbs with postangioplasty residual stenosis >50%. From January 2005 to
      November 2010, 302 EVAR patients (296 men; mean age 74.25 +/- 7.04 years, range
      53-90) with 589 stent-graft limbs (aortomonoiliac stent-graft in 15 patients) who
      had a minimum 6 months of follow-up and a nonstenotic aortic bifurcation were
      selected for this study. Patient demographics, clinical risk factors, iliac
      anatomical features, procedure data, and limb patency were analyzed. Primary
      endpoints were the incidence of limb stenosis >50% and any associated risk
      factors; the secondary endpoint was the primary patency of stent-graft limbs with
      adjunctive stenting. RESULTS: On 3-projection completion angiography, 40 (6.8%)
      limbs presented limb stenosis and were treated with adjunctive stenting; in only
      28 (70%) of these cases was the >50% limb stenosis evident on the AP view.
      According to the degree of preoperative iliac angulation, limb stenosis occurred
      in mild (<60 degrees ), moderate (60 degrees -89 degrees ), and severe (>= 90
      degrees ) angulations in 14 (4.6%), 9 (5.6%), and 17 (13.4%) cases, respectively;
      positive predictors for limb stenosis were severe iliac artery angulation [vs.
      moderate (p = 0.02) and mild (p = 0.001)] and stent-graft limb diameter <16 mm (p
      = 0.02). In the adjunctive stenting group, the mean follow-up was 16.1 months; no
      graft occlusion, graft erosion, or restenosis was seen during follow-up (100%
      primary patency at 12 and 24 months). CONCLUSION: Three-projection completion
      angiography is crucial to identifying limb stenosis, for which adjunctive
      stenting appears to ensure primary patency in midterm follow-up. Preoperative
      iliac artery angulation and small endograft limb diameter are positive prognostic
      factors for limb stenosis >50%.

PMID- 21861752
TI  - Endovascular management of Stanford type a dissection or intramural hematoma with
      a distal primary entry tear.
AB  - A systematic review was conducted of all published cases of endovascular repair
      of retrograde Stanford type A dissection or intramural hematoma to determine
      mortality of this less invasive approach to treatment. Using the PRISMA
      guidelines, databases were searched for any of the terms 'dissect$', 'IMH',
      ('aortic ADJ wall'), 'intramur$', 'intra-mur$' in combination with any of
      'stent$', 'perc$', 'endo$', 'TEVAR' in combination with any of ('type ADJ A'),
      'ascend$' and 'retro$.' The search retrieved 3131 titles, 280 abstracts, and 108
      papers. Of 23 relevant papers selected, mortality data could be extracted from 11
      studies, representing 60 patients. Overall in-hospital mortality was 1.8% (95% CI
      1.2% to 2.4%). Additional all-cause mortality during follow-up was 5.4% (95% CI
      3.5% to 7.2%). The placement of an endoluminal device in the descending thoracic
      aorta to treat a DeBakey IIId/retrograde type A aortic dissection or intramural
      hematoma may be a safer procedure in the short to medium term than open surgical
      replacement of the ascending aorta (with or without the arch). Open surgical
      repair in these patients may therefore be unjustified.

PMID- 21861753
TI  - In vitro analysis of type II endoleaks and aneurysm sac pressurization on
      longitudinal stent-graft displacement.
AB  - PURPOSE: To evaluate the effects of type II endoleaks and sac pressurization on
      stent-graft displacement following endovascular aneurysm repair (EVAR). METHODS:
      Experimental silicone infrarenal aneurysm (6-cm) models were "treated" with a
      Talent stent-graft deployed with 20-mm proximal and distal landing zones. Inflow
      and outflow vessels were created as part of the silicone model to control flow
      into the aneurysm sac. All aneurysm models were uniform, with a diameter neck of
      31 mm, a neck length of 20 mm, and iliac artery diameters of 16 mm. The aortic
      model was secured in a water bath to a pulsatile pump under physiological
      conditions; the output phase ratio (%systole/%diastole) was set at 65/35 with a
      pump rate of 80 beats per minute. Commercially available bifurcated stent-grafts
      were then displaced in vitro utilizing a linear motion apparatus attached to a
      force gauge. The mean arterial pressure (MAP) and pulse pressure (PP) at the
      aortic inflow were 60.1 +/- 3.1 and 38.3 +/- 7.8 mmHg, respectively. Peak force
      to cause initial stent-graft migration with and without a type II endoleak was
      recorded and compared. RESULTS: In aneurysm sacs with no endoleak, the MAP and
      sac PP were 32 +/- 6.4 and 6 +/- 1.3 mmHg, respectively (p<0.01). In aneurysm
      sacs with a type II endoleak, the MAP and sac PP were 54.1 +/- 9.7 and 16.1 +/-
      4.1 mmHg, respectively (p<0.02). Peak force to initiate migration was 16.0 +/-
      1.41 N (range 15-18) with no endoleak vs. 23.2 +/- 2.2 N (range 20-25) in those
      with a type IIa endoleak and 23.5 +/- 2.5 N (range 20-26) in those with a type
      IIb endoleak (p<0.001). CONCLUSION: Type II endoleaks are associated with a
      significantly increased sac pressure. Increased sac pressurization from type II
      endoleaks results in a significantly greater force to displace a stent-graft
      longitudinally. Type II endoleaks may therefore inhibit migration and offer a
      benefit following EVAR; however, clinical correlation of these results is
      required.

PMID- 21861754
TI  - Endovascular repair of a pancreatic allograft mycotic aneurysm: two-year follow
      up.
AB  - PURPOSE: To describe midterm outcome of endovascular stent-graft repair of a
      mycotic aneurysm associated with a peripancreatic allograft abscess after
      transplantation. CASE REPORT: A 46-year-old woman underwent combined kidney and
      pancreas allograft transplantation under heavy immunosuppression. She developed a
      peripancreatic allograft abscess with associated mycotic aneurysm of the
      pancreatic allograft donor iliac artery 2 months after transplantation.
      Endovascular stent-grafts were used to exclude the aneurysm, retaining normal
      pancreatic allograft function over the next 2 years. CONCLUSION: Allograft
      arterial mycotic aneurysm development after transplantation is a rare but
      potentially life-threatening problem. This case suggests that control of a
      mycotic aneurysm may be obtained with stent-grafting in the presence of active
      infection under intense immunosuppression, avoiding allograft pancreatectomy.

PMID- 21861756
TI  - Re: "Endovascular management of arterioenteric fistulas: a systemic review and
      meta-analysis of the literature".

PMID- 21861757
TI  - Mesenchymal stem cells inhibit thymic reconstitution after allogeneic cord blood
      transplantation.
AB  - Cord blood (CB) as a source of stem cells has been a successful addition to the
      field of allogeneic stem cell transplantation (ASCT). The increased human
      leukocyte antigen (HLA) permissiveness of CB grafts has made it possible for more
      patients to undergo treatment. The drawback is that patients suffer from a longer
      period of compromised immunity. We analyzed T-cell receptor excision circles
      (TRECs), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels after cord
      blood transplantation (CBT) in 50 patients transplanted at our center. These
      immunological parameters were compared retrospectively with clinical factors and
      complications. We found that TREC levels after CBT were lower in adults, patients
      with myeloablative conditioning, and in patients with a lower nucleated cell dose
      in the graft. In addition mesenchymal stem cells (MSC) as co-infusion at the time
      of CBT had a negative effect on TREC reconstitution. This was found to be
      associated with decreased overall survival for this patient category. Reduced IgM
      and IgG levels post-CBT were associated with a major AB0 mismatch, and infusion
      of MSCs. Our results highlight the importance of close monitoring of the immune
      reconstitution after CBT. In addition it shows a potentially new suppressive
      effect of MSCs on the immune system.

PMID- 21861758
TI  - Prospective isolation and characterization of bipotent progenitor cells in early
      mouse liver development.
AB  - Outgrowth of the foregut endoderm to form the liver bud is considered the initial
      event of liver development. Hepatic stem/progenitor cells (HSPCs) in the liver
      bud are postulated to migrate into septum transversum mesenchyme at around
      embryonic day (E) 9 in mice. The studies of liver development focused on the mid
      fetal stage (E11.5-14.5) have identified HSPCs at this stage. However, the in
      vitro characteristics of HSPCs before E11.5 have not been elucidated. This is
      probably partly because purification and characterization of HSPCs in early fetal
      livers have not been fully established. To permit detailed phenotypic analyses of
      early fetal HSPC candidates, we developed a new coculture system, using mouse
      embryonic fibroblast cells. In this coculture system, CD13(+)Dlk(+) cells
      purified from mouse early fetal livers (E9.5 and E10.5) formed colonies composed
      of both albumin-positive hepatocytic cells and cytokeratin (CK) 19-positive
      cholangiocytic cells, indicating that early fetal CD13(+)Dlk(+) cells have
      properties of bipotent progenitor cells. Inhibition of signaling by Rho
      associated coiled-coil containing protein kinase (Rock) or by nonmuscle myosin II
      (downstream from Rock) was necessary for effective expansion of early fetal
      CD13(+)Dlk(+) cells in vitro. In sorted CD13(+)Dlk(+) cells, expression of the
      hepatocyte marker genes albumin and alpha-fetoprotein increased with fetal liver
      age, whereas expression of CK19 and Sox17, endodermal progenitor cell markers,
      was highest at E9.5 but decreased dramatically thereafter. These first
      prospective studies of early fetal HSPC candidates demonstrate that bipotent
      stem/progenitor cells exist before E11.5 and implicate Rock-myosin II signaling
      in their development.

PMID- 21861759
TI  - A model of early human embryonic stem cell differentiation reveals inter- and
      intracellular changes on transition to squamous epithelium.
AB  - The molecular events leading to human embryonic stem cell (hESC) differentiation
      are the subject of considerable scrutiny. Here, we characterize an in vitro model
      that permits analysis of the earliest steps in the transition of hESC colonies to
      squamous epithelium on basic fibroblast growth factor withdrawal. A set of
      markers (GSC, CK18, Gata4, Eomes, and Sox17) point to a mesendodermal nature of
      the epithelial cells with subsequent commitment to definitive endoderm (Sox17,
      Cdx2, nestin, and Islet1). We assayed alterations in the transcriptome in
      parallel with the distribution of immunohistochemical markers. Our results
      indicate that the alterations of tight junctions in pluripotent culture precede
      the beginning of differentiation. We defined this cell population as "specified,"
      as it is committed toward differentiation. The transitional zone between
      "specified" pluripotent and differentiated cells displays significant up
      regulation of keratin-18 (CK18) along with a decrease in the functional activity
      of gap junctions and the down-regulation of 2 gap junction proteins, connexin 43
      (Cx43) and connexin 45 (Cx45), which is coincidental with substantial elevation
      of intracellular Ca2+ levels. These findings reveal a set of cellular changes
      that may represent the earliest markers of in vitro hESC transition to an
      epithelial phenotype, before the induction of gene expression networks that guide
      hESC differentiation. Moreover, we hypothesize that these events may be common
      during the primary steps of hESC commitment to functionally varied epithelial
      tissue derivatives of different embryological origins.

PMID- 21861761
TI  - Effects of intrabone marrow-bone marrow transplantation plus adult thymus
      transplantation on survival of mice bearing leukemia.
AB  - We recently found that allogeneic intrabone marrow-bone marrow transplantation
      (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor is
      effective in mice bearing solid tumors. In the current study, we examined the
      effects of this strategy on the survival of mice with leukemia. One week after
      intravenous injection of 1*10(6) leukemic cells (EL-4, H-2(b)) into 8-week-old B6
      (H-2(b)) mice, the mice were 8 Gy irradiated and transplanted with 1*10(7) bone
      marrow cells (BMCs) from 8-week-old BALB/c mice (H-2(d)) by IBM-BMT with or
      without donor lymphocyte infusion (DLI) or ATT. All the mice without treatment
      died within 70 days after injection of EL-4. About 40% of those treated with IBM
      BMT alone died within 100 days due to tumor relapse. In contrast, those treated
      with IBM-BMT+DLI or ATT showed the longest survival rate without relapse of
      leukemia. In addition, the former showed less graft versus host disease (GVHD)
      than the latter. The mice treated with IBM-BMT+ATT also showed an intermediate
      percentage of effector memory (EM) and central memory (CM) cells between those
      treated with BMT alone and those treated with IBM-BMT+DLI. The numbers and
      functions of T cells increased in those treated with IBM-BMT+ATT with interleukin
      2 and interferon-gamma production. These results suggest that IBM-BMT+ATT is
      effective in the treatment of leukemia with strong graft versus leukemia without
      increased risk of GVHD.

PMID- 21861762
TI  - Perceptions of dental aesthetics of Class III and anterior open bite
      malocclusions: a comparison between 10- to 11-year-old schoolchildren and
      orthodontists.
AB  - OBJECTIVE: To compare perceptions of dental aesthetics of Class III and anterior
      open bite (AOB) malocclusions between 10- to 11-year-old Birmingham
      schoolchildren and orthodontists. MATERIALS AND METHODS: Thirty-one orthodontists
      practicing in Birmingham (UK) and 383 school children aged 10-11 years from a
      random and representative sample of seven primary schools in South Birmingham
      participated in the study. Participants were asked to assess five anterior
      photographs of the dentition representing varying degrees of aesthetic impairment
      of Class III and AOB malocclusions. Perceptions of dental aesthetics were
      determined using the aesthetic component (AC) of the Index of Orthodontic
      Treatment Need (IOTN). RESULTS: Perceptions of dental aesthetics were similar
      among males and females (P > .05). Both groups allocated the highest median AC
      score to the photo representing severe Class III malocclusion and the lowest to
      the photo representing mild Class III and AOB malocclusion. Differences in
      perceived dental aesthetics were significant for photos representing severe Class
      III and moderate AOB malocclusions, with orthodontists perceiving greater
      aesthetic impairment for severe Class III and schoolchildren for moderate AOB,
      respectively (P < .05). CONCLUSIONS: Schoolchildren and orthodontists perceived
      Class III malocclusions to have greater aesthetic impairment compared to AOB
      malocclusions. Surprisingly, none of the median AC scores allocated to the five
      photos were in the "Definite need" for treatment category. The IOTN may not be
      sensitive to these types of malocclusions. This finding merits further
      investigation.

PMID- 21861760
TI  - Continuous antagonism by Dkk1 counter activates canonical Wnt signaling and
      promotes cardiomyocyte differentiation of embryonic stem cells.
AB  - Embryonic stem (ES) cells give rise to mesodermal progenitors that differentiate
      to hematopoietic and cardiovascular cells. The wnt signaling pathway plays
      multiple roles in cardiovascular development through a network of intracellular
      effectors. To monitor global changes in wnt signaling during ES cell
      differentiation, we generated independent ES cell lines carrying the luciferase
      gene under promoters that uniquely respond to specific wnt pathway branches. Our
      results show that successive, mutually exclusive waves of noncanonical and
      canonical wnt signaling precede mesoderm differentiation. Blocking the initial
      noncanonical JNK/AP-1 signaling with SP60125 aborts cardiovascular
      differentiation and promotes hematopoiesis, whereas interference with the
      subsequent peak of canonical wnt signaling using Dkk1 has the opposite effect.
      Dkk1 blockade triggers counter mechanisms that lead to delayed and extended
      activation of canonical wnt signaling and mesoderm differentiation that appear to
      favor the cardiomyocytic lineage at the expense of hematopoietic cells. The
      cardiomyocytic yield can be further enhanced by overexpression of Wnt11 leading
      to approximately 95-fold enrichment in contracting cells. Our results suggest
      that the initial noncanonical wnt signaling is necessary for subsequent
      activation of canonical signaling and that the latter operates under a regulatory
      loop which responds to suppression with hyperactivation of compensatory
      mechanisms. This model provides new insights on wnt signaling during ES cell
      differentiation and points to a method to induce cardiomyocytic differentiation
      without precise timing of wnt signaling manipulation. Taking into account the
      heterogeneity of pluripotent cells, these findings might present an advantage to
      enhance the cardiogenic potential of stem cells.

PMID- 21861763
TI  - Impedance-based surveillance of transient permeability changes in coronary
      endothelial monolayers after exposure to ionizing radiation.
AB  - The relative radiation sensitivities of the various compartments of the heart are
      poorly characterized. Cardiac fibrosis is a common side effect of radiotherapy,
      suggesting that endothelial barrier function is an important factor in radiation
      induced pathology. We employed Electric Cell Substrate Impedance Sensing (ECIS)
      to assess cytoskeletal rearrangement, permeability changes and endothelial
      barrier function changes in response to radiation in studies of human coronary
      arterial endothelial cells (HCAECs). A 5-Gy dose of gamma radiation resulted in a
      significant sixfold transient decrease in transmonolayer resistance 3 h
      postirradiation (P = 0.001). This decrease in resistance coincided with changes
      in fluorescent tracer flux (P = 0.05) and display of an actin bundling phenotype.
      After irradiation, decreases in wound healing (P = 0.03) and micromotion within
      the monolayer (P = 0.02) were also observed. Time-lapse video studies confirmed
      that the monolayer is dynamic and showed that cells are extruded from the
      monolayer at a higher frequency after irradiation. These findings suggest that
      perturbed endothelial barrier function in the heart can occur at lower doses of
      gamma radiation than previously reported.

PMID- 21861764
TI  - Nucleocapsid protein VP15 of White spot syndrome virus colocalizes with the
      nucleolar proteins nucleolin and fibrillarin.
AB  - The core nucleocapsid protein VP15 of White spot syndrome virus (WSSV) was shown
      to interact with DNA and predicted to be involved in the packaging of the WSSV
      genome. In the present study, we explored the colocalization of VP15 with several
      nuclear proteins in insect cells. The results showed that the VP15 completely
      colocalized with nucleolin and fibrillarin, suggesting that VP15 is a nucleolar
      localization protein and plays an important role in the life cycle of WSSV in
      host cells.

PMID- 21861765
TI  - Detection of Aspergillus in lung and other tissue samples using the MycAssay
      Aspergillus real-time PCR kit.
AB  - The MycAssayTM Aspergillus real-time PCR kit was tested on tissues from patients
      with invasive fungal infections. Tissue samples from nine organ transplant
      recipients and 33 patients with haematological malignancy were from lung (n =
      30), skin (n = 4), and others. Samples were preprocessed with proteinase K and
      lyticase, followed by DNA extraction and real-time PCR. For all samples, the
      sensitivity of the MycAssay Aspergillus test was 82% and specificity 79% relative
      to microscopy and 90% and 64%, respectively, compared with Aspergillus culture.
      The positive predictive value and negative predictive values compared with
      culture were 69% and 88% and were 88% and 69% compared with microscopy,
      respectively. The MycAssay Aspergillus test detected tissue invasive infections
      with Aspergillus fumigatus , Aspergillus flavus , and Aspergillus terreus.

PMID- 21861766
TI  - Association between obesity and depression: evidence from a longitudinal sample
      of the elderly in Taiwan.
AB  - OBJECTIVES: Obesity has been identified as an epidemic worldwide. In Taiwan, the
      highest prevalence of obesity is observed in adults age >=65. This article
      investigates the effects of body weight status on the likelihood of depression
      among the elderly in Taiwan. METHOD: A longitudinal sample of the elderly (1351
      males and 1165 females) interviewed in both the 1999 and 2003 Surveys of Health
      and Living Status of the Elderly in Taiwan is used. A random effect logit model
      is estimated to examine the effects of body weight status, lifestyle, and socio
      demographic characteristics on the likelihood of depression. RESULTS: About 10.4%
      of the elderly men are overweight and 13.4% are obese in 2003. A higher
      prevalence of obesity is found among elderly women, with 19.3% being overweight
      and 26.4% obese. Elderly men who are underweight are more likely to be depressed
      (odds ratio; OR = 2.36) than those from other weight categories, while overweight
      and obese women are less likely to be depressed (ORs = 0.72 and 0.61) than
      elderly women of the normal weight category. CONCLUSIONS: In contrast to most
      findings for the Western countries, a negative association between obesity and
      depression of the elderly is evident in Taiwan. The different findings between
      Western and Asian countries may be due to the cultural differences. Unlike the
      Western countries that stigmata are attached to excessive overweight, being
      overweight is not a symbol of unhealthiness because only the wealthy can afford
      to eat more and put on more weight in the Chinese society.

PMID- 21861767
TI  - Essential oil composition of Eucalyptus procera Dehnh. leaves from central Iran.
AB  - The chemical composition of the essential oil of leaves of Eucalyptus procera
      Dehnh., cultivated in central Iran, was obtained by hydrodistillation and
      analysed by GC-MS. Forty-five constituents representing 99.6% of the total oil
      were identified. The main constituents of the oil were found to be 1,8-cineole
      (35.9%), alpha-pinene (25.6%) and viridiflorol (7.7%). Other representative
      compounds were identified as alpha-terpineol (3.6%), aromadendrene (3.5%) and
      trans-pinocarveol (3.0%).

PMID- 21861768
TI  - Fibrinolytic activity of kaempferol isolated from the fruits of Lagenaria
      siceraria (Molina) Standley.
AB  - This study was undertaken to isolate a flavonol, kaempferol, from the fruits of
      Lagenaria siceraria (bottle gourd) as a sole compound and to explore the
      fibrinolytic potential of the methanolic extract of the fruits of L. siceraria
      and the isolated compound using their in vitro activity. The fibrinolytic
      activity in terms of percentage of plasma clot liquefaction was determined by
      plasma clot lysis at 37 degrees C in 24 h. The fibrinolytic activity of both
      substances was compared to the well-known thrombolytic agent streptokinase
      (30,000 IU). The percentage of fibrinolytic activity of the extract and isolated
      compound were found to be 54.72 +/- 0.7210 and 77.37 +/- 1.3010, respectively.
      Streptokinase was considered as the standard fibrinolytic enzyme for comparative
      purposes and had 91.46 +/- 0.7625% fibrinolytic activity. The conclusion drawn in
      our study after testing the hypothesis by experimental procedures is that in
      vitro fibrinolytic activity on plasma clots is an inherent property of kaempferol
      isolated from the fruits of L. siceraria, and its comparison with streptokinase
      is a new aspect for further study.

PMID- 21861769
TI  - In vitro antioxidant activity of the water and ethanol extracts of Forsythia
      koreana flowers.
AB  - The antioxidant activities of the water and ethanol extracts of F. koreana
      flowers were evaluated using DPPH, superoxide anion (*O(-2)), and nitric oxide
      (*NO) radical scavenging activity assays. The SC(50) values of the water extract
      of F. koreana on DPPH, *O(-2) and *NO were 48.39, 24.36 and 100.21 ug mL(-1),
      respectively. The SC(50) values of the ethanol extract of F. koreana on the
      aforesaid free radicals were 57.50, 49.00 and 146.08 ug mL(-1), respectively.
      Further, the total phenolic contents of both extracts were determined and
      expressed as milligram gallic acid equivalent (GAE) per gram of extract. The
      water extract exhibited a higher phenolic content (113.78 mg GAE g(-1)), while
      the ethanol extract showed 94.53 mg GAE g(-1). Our findings demonstrate that the
      water and ethanol extracts of F. koreana flowers might be potential natural
      sources of antioxidative additives for use in the food and other allied
      industries.

PMID- 21861770
TI  - Atopy is associated with asthma in adults living in rural and urban southwestern
      Nigeria.
AB  - RATIONALE: Factors affecting the course of asthma are not clearly understood in
      rural and urban communities within low-resource countries. Furthermore, the
      interactions between atopy, environmental exposure, and helminthic infections in
      modulating asthma have not been well investigated. OBJECTIVES: To conduct a
      feasibility study to examine the relationship between atopy and asthma in adults
      at two rural Health Centers and urban university college hospital in southwestern
      Nigeria. METHODS: A convenient sample of 55 consecutive patients with stable
      physician-diagnosed asthma and 55 age-matched nonasthmatic controls seen at the
      outpatient clinics in two rural Health Centers and an urban university hospital
      were enrolled. All subjects underwent blood test, allergy skin test, and stool
      examination for ova and parasites. Wilcoxon sign-rank tests were used to compare
      serum eosinophilia and allergy skin test between the two groups. RESULTS:
      Asthmatics in both urban and rural settings had significantly more positive skin
      reactions to house dust mite, cockroach, mold, and mouse epithelium than
      nonasthmatic controls (p < .05). Mean total serum IgE was also significantly
      higher in asthmatics than in nonasthmatic controls (360 vs. 90 IU/L, p <.001).
      Stool parasitemia was infrequent in both groups and not statistically
      significant. CONCLUSION: Atopy is associated with adult asthma in southwest
      Nigeria. Larger studies to confirm the nature of this association and to examine
      the role of helminthic infection and other environmental factors on the
      expression of asthma are needed.

PMID- 21861771
TI  - Sertraline improves the somatic and psychological symptoms of the climacteric
      syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of sertraline versus placebo in the
      management of somatic and psychological complaints of the climacteric syndrome.
      METHODS: We conducted a randomized, double-blind, placebo-controlled trial. A
      total of 44 women with moderate to severe complaints, defined as 16 or more
      points according to the Menopause Rating Scale (MRS) considering only the
      psychological and somatic domains, were incorporated into the trial and
      randomized to receive either sertraline (50 mg/day) or placebo. Both groups were
      evaluated at baseline and after 45 and 90 days of treatment. A reduction of 50%
      or more in the score was considered as a successful response. RESULTS: Thirty
      three patients finished the trial (16 in the sertraline group and 17 in the
      placebo group), showing an odds ratio of 7.94 (95% confidence interval 1.3-57.3),
      p = 0.0038 for the sertraline group, in spite of the prominent effect of placebo.
      CONCLUSIONS: Sertraline was more effective than placebo in the management of the
      somatic and psychological complaints of the climacteric syndrome.

PMID- 21861772
TI  - Episodic repetitive thought: dimensions, correlates, and consequences.
AB  - Repetitive thought (RT) - attentive, prolonged, or frequent thought about oneself
      and one's world - plays an important role in many models of psychological and
      physical ill health (e.g., rumination and worry), as well as models of recovery
      and well-being (e.g., processing and reminiscing). In these models, repetitive
      thought is typically treated as stable or trait-like. In contrast, episodic RT
      reflects what people have "on their minds" at a particular point in time. In four
      studies, young women (N=94), college students (N=166), first-year law students
      (N=73), and older adults (N=174) described their episodic RT, which was then
      rated for qualities including valence, purpose, and theme. Episodic RT valence
      was associated with mood and depressive symptoms both between (Studies 1-4) and
      within people (Studies 3-4), and it mediated the effects of dispositional coping
      through emotional approach (Study 1). The effect of episodic RT valence in turn
      was moderated by other properties of episodic RT, including purpose, "trait"
      valence, and theme (Studies 1-4). The study of episodic RT complements that of
      trait RT and allows for observations of how RT and psychological adjustment
      change in concert and in context, as well as examining how the RT qualities that
      are not reflected in trait measures affect adjustment.

PMID- 21861773
TI  - Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx)
      tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis
      inducing environment.
AB  - It has been reported that the arylhydrocarbon receptor (AHR) is overexpressed in
      certain types of breast tumors. However, so far no concrete evidence has been
      provided yet as to why and how the overexpressed AHR in those cancer cells is
      functionally activated without exogenous ligands. Here we show that the AHR was
      functionally activated when estrogen receptor-negative, AHR overexpressing
      MCF10AT1 human breast cancer cells (designated P20E) were subjected to serum
      starvation. Transfection of cells with ETK-KQ, a plasmid for kinase-dead
      epithelial and endothelial tyrosine kinase (ETK), attenuated this AHR activation.
      Artificial over-expression of ETK in P20E cells through transfection with wild
      type ETK plasmid (ETK-wt) caused up-regulation of cytochrome P4501a1 (CYP1A1; a
      marker of functional activation of AHR). Furthermore, ablation of ETK expression
      by a specific antisense oligonucleotide or AG879, a specific inhibitor of ETK
      kinase suppressed activation of AHR induced by omeprazole, a strong ligand
      independent activator of AHR. Activation of ETK in those cells conferred them
      resistance to UVB- as well as doxorubicin-induced apoptosis, both of which were
      reversed by ETK-KQ. Together, these findings support our conclusion that ETK is
      the tyrosine kinase responsible for the functional activation of the AHR in these
      mammary epithelial cells.

PMID- 21861774
TI  - Evaluation of proton beam radiation sensitivity of proliferating choroidal
      endothelial and retinal ganglion cells with clonogenic assay.
AB  - CONTEXT: Proton beam therapy offers the advantage of precise delivery with
      limited damage to the healthy tissue and is being tested in the management of
      exudative age-related macular degeneration (AMD). However, the dosages tested are
      empirical and not based on preclinical studies. OBJECTIVE: In this study we
      evaluated the effects of varying doses of proton beam radiation on choroidal
      endothelial cells (CECs) and retinal ganglion cells (RGCs) using clonogenic assay
      to determine differential sensitivity. MATERIALS AND METHODS: Each cell type has
      different efficiency to replicate (plating efficiency (PE)). PE of CEC (RF/6A)
      and RGC (RGC-5) grown in culture flasks was determined by plating 250 cells each
      (without any treatment) and counting the number of colonies after 13 days.
      Radiation induced sensitivity was determined by exposing the semi-confluent RF/6A
      and RGC-5 cells to proton beam at the doses of 0 (control), 2, 4, 8 and 12 cobalt
      gray equivalent (CGE). The ability of the cells to repair and replicate to form
      colonies were analyzed 13 days after radiation with crystal violet stain and the
      survival ratio was calculated. The significance of survival was analyzed using
      ANOVA (Graphpad Instat.3). RESULTS: The PE of CEC and RGC was 12.96 +/- 0.29% and
      40.7 +/- 1.48%, respectively. A survival ratio of CEC at 2, 4, 8 and 12 CGE
      proton radiation was 66.0 +/- 8.6%, 44.3 +/- 6.5%, 7.6 +/- 0.3% and 1.14 +/-
      0.06% on exposure to 2, 4, 8 and 12 CGE proton radiation, respectively, p <
      0.01). Survival ratio of RGC was 71.1 +/- 22.4% (p = 0.05), 40.2 +/- 7.9%, 8.89
      +/- 2.6% and 0.78 +/- 0.31% at 2, 4, 8 and 12 CGE dosages (p < 0.001).
      DISCUSSION: CEC showed dose-dependent decrease in survival rate with values
      attaining significance at all radiation dosages. In contrast, RGC was
      comparatively radio resistant and were able to replicate at lower doses and
      sensitive at higher doses after proton beam radiation. CONCLUSION: Since CECs
      proliferate during neovascularization, this clonogenic assay is a useful assay to
      assess the sensitivity of CEC to radiation. This study identified that CEC were
      more sensitive to proton beam radiation than RGC at all doses. This may provide a
      therapeutic window for administration of proton beam radiation in the management
      of AMD.

PMID- 21861775
TI  - Nonspecific immune responses of Cathranthus roseus in Oreochromis mossambicus.
AB  - The present study was performed to determine the efficacy and immune stimulatory
      effects of crude and water-soluble leaf fraction of Cathranthus roseus in
      Oreochromis mossambicus. Intraperitoneal injection method was used to
      administrate the drugs and Sheep Red Blood Cells (SRBC) which is used as an
      antigen. Lysozyme assay, plate hole diffusion assay, phytochemical analysis and
      antimicrobial activity screening methods was used to confirm the drug immune
      responses. In vivo experiments show the significant enhancement of non-specific
      immune response such as lysozymal activity. Increase in the WBC count was also
      noticed when animals were exposed into the environment containing crude extract
      (CE) and water-soluble fraction (WSF) of the target drug. Moreover, biochemical
      analysis of C. roseus reveals the presence of some important secondary
      metabolites such as alkaloids, tannins, flavonoids and sterols. In vitro
      antibacterial activity of different concentration CE and WSF against Aeromonas
      hydrophila had a potential drug activity. Cathranthus roseus has induced the
      nonspecific immune responses in Oreochromis mossambicus. Our results suggest the
      conserved roles of this immune stimulant applicable to higher vertebrates at the
      infection stage.

PMID- 21861776
TI  - Functional analysis of HIV type 1 Nef gene variants from adolescent and adult
      survivors of perinatal infection.
AB  - Throughout the world, infants and children with HIV-1 infection are increasingly
      surviving into adolescence and adulthood. As HIV Nef is an important determinant
      of the pathogenic potential of the virus, we examined nef alleles in a cohort of
      extreme long-term survivors of HIV infection (average age of 16.6 years) to
      determine if Nef defects might have contributed to patient survival. HIV nef gene
      sequences were amplified for phylogenetic analysis from 15 adolescents and adults
      infected by mother-to-child transmission (n=10) or by blood transfusion (n=5).
      Functional analysis was performed by inserting patient-derived nef sequences into
      an HIV-derived vector that permits simultaneous evaluation of the impact of the
      Nef protein on MHC-I and CD4 cell surface expression. We found evidence of
      extensive nef gene diversity, including changes in known functional domains
      involved in the downregulation of cell surface MHC-I and CD4. Only 3 of 15
      individuals (20%) had nef alleles with a loss of the ability to downregulate
      either CD4 or MHC-I. Survival into adulthood with HIV infection acquired in
      infancy is not uniformly linked to loss of function in nef. The Nef protein
      remains a potential target for immunization or pharmacologic intervention.

PMID- 21861777
TI  - Measurements of immune responses for establishing correlates of vaccine
      protection against HIV.
AB  - Well-defined correlates of protective immunity are an essential component of
      rational vaccine development. Despite years of basic science and three HIV
      vaccine efficacy trials, correlates of immunological protection from HIV
      infection remain undefined. In December 2010, a meeting of scientists engaged in
      basic and translational work toward developing HIV-1 vaccines was convened. The
      goal of this meeting was to discuss current opportunities and optimal approaches
      for defining correlates of protection, both for ongoing and future HIV-1 vaccine
      candidates; specific efforts were made to engage young scientists. We discuss
      here the highlights from the meeting regarding the progress made and the way
      forward for a protective HIV-1 vaccine.

PMID- 21861778
TI  - Characterization of ethyl cellulose polymer.
AB  - Ethyl cellulose (EC) polymer was characterized for its property before
      considering the interactions with the plasicizer. Ethocel Std.10 FP Premium from
      Dow chemical company USA was tested for its solubility, morphology and thermal
      properties. Seven percentage of EC solution in ethanol was found to be the right
      viscosity used to prepare the film. The EC polymer and EC film without any
      plasticizers showed almost identical thermal behavior, but in X-ray diffraction
      showed different arrangements of crystallites and amorphous region. Dynamic
      mechanical analysis of film showed that without a plasticizer, EC film was not
      flexible and had very low elongation with high applied force. The aim of the work
      was to avoid using the commercially available EC dispersions Surelease(r) and
      Aquacoat(r); both already have additives on it. Instead, Ethocel EC polymer
      (powder) was characterized in our laboratory in order to find out the properties
      of polymer before considering the interactions of the polymer with various
      plasticizers. 

PMID- 21861779
TI  - Bone marrow-derived mesenchymal stromal cells enhance chimeric vessel development
      driven by endothelial cell-coated microtissues.
AB  - Adding bone marrow-derived mesenchymal stromal cells (bmMSCs) to endothelialized
      collagen gel modules resulted in mature vessel formation, presumably caused in
      part by the observed display of pericyte-like behavior for the transplanted
      GFP(+) bmMSCs. A previous study determined that rat aortic endothelial cells
      (RAECs) delivered on the surface of small (~0.8 mm long*0.5 mm diameter) collagen
      gel cylinders (microtissues, modular tissue engineering) formed vessels after
      transplantation into immunosuppressed Sprague-Dawley (SD) rats. Although the
      RAECs formed vessels in this allogeneic transplant model, there was a robust
      inflammatory response and the vessels that formed were leaky as shown by
      microcomputed tomography (microCT) perfusion studies. In vitro assays showed that
      SD rat bmMSCs embedded into the collagen gel modules increased the extent of EC
      proliferation and enhanced EC sprouting. In vivo, although vessel number was not
      affected, the new vessels formed by the bmMSCs and RAECs were more stable and
      leaked less in the microCT perfusion analysis than vessels formed by implanted
      RAECs alone. Addition of the bmMSCs also decreased the total number of CD68(+)
      macrophages that infiltrated the implant and changed the distribution of CD163(+)
      (M2) macrophages so that they were found within the newly developed vascularized
      tissue. Most interestingly, the bmMSCs became smooth muscle actin positive and
      migrated to surround the EC layer of the vessel, which is the location typical of
      pericytes. The combination of these two effects was presumed to be the cause of
      improved vascularity when bmMSCs were embedded in the EC-coated modules. Further
      exploration of these observations is warranted to exploit modular tissue
      engineering as a means of forming large vascularized functional tissues using
      microtissue components.

PMID- 21861780
TI  - Rates of apparently abnormal MMPI-2 profiles in the normal population.
AB  - MMPI-2 standardization data were re-sampled using Monte Carlo simulations to
      estimate the base rate of apparently abnormal scores expected by chance in the
      normal population when multiple scales are interpreted. 36.8% of normal adults
      are likely to obtain a score that would otherwise be considered clinically
      significant at 65T on one or more of the 10 Clinical scales. The normal incidence
      of at least one apparently abnormal score was 38.3% on the Content and 55.1% on
      the Supplementary scales. When the Clinical, Supplementary, and Content scales
      and subscales are interpreted together, at least three seemingly meaningful
      scores will be found in 47.4% of perfectly normal individuals, and five or more
      scales that appear to be clinically significant can be expected in 30.1% of cases
      that are actually unremarkable. These results imply that the number of MMPI-2
      scales that can be meaningfully interpreted in clinical practice is limited, and
      that high T-scores are necessary for an adequate level of confidence even when
      interpretation is appropriately limited to the Clinical scales.

PMID- 21861783
TI  - Graph theoretical analysis of human brain structural networks.
AB  - There is a growing interest in exploring the connectivity patterns of the human
      brain. Specifically, the utility of noninvasive neuroimaging data and graph
      theoretical analysis have provided important insights into the anatomical
      connections and topological pattern of human brain structural networks in vivo.
      This review focuses on recent methodological and application studies, utilizing
      graph theoretical approaches, on brain structural networks with structural
      magnetic resonance imaging (MRI) and diffusion MRI. These studies showed many
      nonrandom properties of structural brain networks, such as small-worldness,
      modularity, and highly connected hubs. Importantly, topological organization of
      the networks shows changes during normal development, aging, and neuropsychiatric
      diseases. Network structures have also been found to correlate with behavioral or
      cognitive functions, which imply their associations with functional dynamics.
      These advances not only help us to understand how the healthy human brain is
      structurally organized, but also provide a novel insight into the biological
      mechanisms of brain disorders. Future studies will involve the combination of
      structural/diffusion MRI and functional MRI, to realize how the structural
      connectivity patterns of the brain underlie its functional states, and will
      explore whether graph theoretical analysis of structural brain networks could
      serve as potential imaging biomarkers for disease diagnosis and treatment.

PMID- 21861801
TI  - Therapy for non-clear cell histologies in renal cancer.
AB  - The advent of targeted systemic therapies has significantly improved treatment
      options for patients with metastatic renal cell carcinoma (RCC). Multiple agents
      that inhibit angiogenesis cell growth and proliferation via the VEGF and mTOR
      (TORC1) pathways have been USFDA-approved for locally advanced or metastatic
      renal cell carcinoma in recent years although the majority of clinical trials
      have focused only on clear cell RCC. While clear cell RCC is the most common
      histologic subtype nearly 25% of RCC cases are histologic variants representing a
      diverse group of diseases with different prognoses underlying biology and
      molecular targets and therapies. This review will focus on the incidence clinical
      and pathologic features pathogenesis and treatment strategies of non-clear cell
      RCC in both the adjuvant and metastatic setting. These non-clear cell subtypes
      include papillary type 1 and type 2 chromophobe translocation carcinoma and
      collecting duct RCC. Controlled studies in these relatively rare subgroups are
      needed to inform upon clinical practice which is currently based on small series
      of uncontrolled studies. Ongoing clinical trials and areas of future research
      will be discussed.

PMID- 21861802
TI  - Renal cancer: is targeted therapy really empiric?

PMID- 21861803
TI  - Effect of tetracyclines on IgE allergic responses and asthma.
AB  - There are no current therapies that specifically target IgE production in human
      allergic disease. We found that tetracyclines and chemically modified
      tetracyclines (CMT) that lack antibiotic activity prevent IgE production, making
      them ideal candidates for anti-allergy therapy. This is based on our findings
      that minocycline treatment of allergic asthmatic humans significantly improves
      their asthma symptoms, reduces their oral steroid requirements, and strongly
      suppresses their ongoing IgE responses. Tetracyclines and CMT also suppress
      ongoing IgE responses of BPO-KLH sensitized mice in vivo and in vitro and humans
      IgE responses in vitro. We also found that highly increased levels of
      phosphorylated p38 MAP kinase, but not phosphorylated JNK or ERK, are expressed
      by blood T and B cells and monocytes of allergic asthmatic humans. Levels of
      phosphorylated p38 MAP kinase, but not ERK or JNK, correlated with their IgE.
      Tetracyclines significantly suppressed expression of phosphorylated p38 MAP
      kinase by CD4+ and CD8+ T cells but not B cells or monocytes in vivo and in
      vitro. Our findings open the door to development of new drugs and patents,
      especially for CMTs that lack antibiotic activity (US 7649113), for treatment of
      human allergic disease.

PMID- 21861782
TI  - The role of tumor necrosis factor receptor superfamily members in mammalian brain
      development, function and homeostasis.
AB  - Tumor necrosis factor receptor superfamily (TNFRSF) members were initially
      identified as immunological mediators, and are still commonly perceived as
      immunological molecules. However, our understanding of the diversity of TNFRSF
      members' roles in mammalian physiology has grown significantly since the first
      discovery of TNFRp55 (TNFRSF1) in 1975. In particular, the last decade has
      provided evidence for important roles in brain development, function and the
      emergent field of neuronal homeostasis. Recent evidence suggests that TNFRSF
      members are expressed in an overlapping regulated pattern during neuronal
      development, participating in the regulation of neuronal expansion, growth,
      differentiation and regional pattern development. This review examines evidence
      for non-immunological roles of TNFRSF members in brain development, function and
      maintenance under normal physiological conditions. In addition, several aspects
      of brain function during inflammation will also be described, when illuminating
      and relevant to the non-immunological role of TNFRSF members. Finally, key
      questions in the field will be outlined.

PMID- 21861804
TI  - ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus:
      is Nrf2 a potential target for the treatment?
AB  - Although the clear mechanism of T2DM is still to be elucidated, it has been well
      established that reactive oxygen species (ROS) derived from multiple sources
      plays a causal role in multiple types of insulin resistance and contributes to
      beta-cell dysfunction thus enhances the development and progression of T2DM. What
      is incomprehensible is that the detrimental ROS also plays a substantial role in
      the normal insulin signal transduction and glucose-stimulated insulin secretion
      (GSIS) in beta-cell, which forces us to re-recognize the role of ROS under
      physiological and pathological conditions in a more broad way. Redox homeostasis
      is tightly controlled by the transcriptional factor nuclear factor erythroid 2
      related factor 2 (Nrf2), whose abnormality is believed to be related with
      diabetes. Accumulating evidences suggest that there are important cross-talks
      between Nrf2 and PPARgamma, PGC1alpha, PI3K/Akt on regulating antioxidant enzymes
      and the development of diabetes. Therefore, these evidences indicate that Nrf2
      may be a critical element in taking survival and death decisions when cells are
      exposed to an oxidant environment. In conclusion, enhancing GSIS and insulin
      sensitivity through the regulation of Nrf2 levels is a potential avenue for
      developing new therapeutics. Nrf2 may become a promising target for the treatment
      of T2DM.

PMID- 21861805
TI  - Potential new anticancer molecular targets for the treatment of human testicular
      seminomas.
AB  - In the last years novel therapeutic approaches for the treatment of cancer have
      been proposed: specific inhibitors of serine/threonine and tyrosine kinases,
      angiogenesis inhibitors, antibodies against receptors/surface molecules on cancer
      cells, gene therapy approaches and others. In a lot of cases the clinical trials
      have confirmed the efficacy of these approaches. Here, we will review the
      discovered new potential molecular targets for the treatment of human testicular
      seminomas.

PMID- 21861806
TI  - Natural products with antitumor activity from endophytic fungi.
AB  - Endophytic fungi are a seemingly inexhaustible source of novel bioactive natural
      products. Currently, more than 140 fungal metabolites have shown confirmed
      activity in tumor cell line bioassays. We present the chemical structures of
      these antitumor metabolites, their corresponding fungal endophytes and host
      plants, and the activities they exhibited, and briefly discuss some of their
      action mechanisms. This review emphasizes the role of endophytic fungi as an
      important source of leads for drug discoveries.

PMID- 21861807
TI  - Recent developments in the medicinal chemistry and therapeutic potential of
      dihydroorotate dehydrogenase (DHODH) inhibitors.
AB  - Dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme
      that catalyzes fourth reaction of pyrimidine de-novo synthesis. Pyrimidine bases
      are essential for cellular metabolism and cell growth, and are considered as
      important precursors used in DNA (thymine and cytosine), RNA (uracil and
      cytosine), glycoproteins and phospholipids biosynthesis. The significance of
      pyrimidines biosynthesis in DNA and RNA makes them ideal targets for
      pharmacological intervention. Inhibitors of DHODH have proven efficacy for the
      treatment of malaria, autoimmune diseases, cancer, rheumatoid arthritis and
      psoriasis. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH)
      represents an important target for the treatment of malaria. Many of the
      clinically relevant anti-tumor and immunosuppressive drugs target human
      dihydroorotate dehydrogenase (hDHODH), and the two most promising drugs of such
      kinds are brequinar (antitumor and immunosuppressive) and leflunomide
      (immunosuppressive). X-ray crystal structures of DHODH in complex with inhibitors
      reveal common binding region shared by each inhibitor. A number of compounds are
      identified by high-throughput screening (HTS) of chemical libraries and structure
      based computational approaches as selective DHODH inhibitors. Based upon the
      understanding of molecular interaction of DHODH inhibitors with binding site,
      some of the common structural features are identified like ability of compounds
      to interact with ubiquinone (CoQ) binding site and substituents linked to a
      variety of heterocyclic and heteroaromatic rings responsible for H-bonding with
      binding site. These findings provide new approaches to design DHODH inhibitors
      and highlights DHODH as a target for chemotherapeutics. This review is mainly
      focused on the recent developments in the medicinal chemistry and therapeutic
      potential of DHODH inhibitors as a target for drug discovery.

PMID- 21861808
TI  - Give boron a chance: boron containing compounds reach ionotropic and metabotropic
      transmembrane receptors.
AB  - The ligand-gated ion channels and seven transmembrane domain receptors are the
      greatest families of transmembrane receptors (TMR) expressed in mammalians and
      the major target of current available drugs. Recently, boron containing compounds
      (BCC) have shown capability of acting as ligands on these targets. This mini
      review is focused on the description of BCC that target TMR which were evaluated
      under experimental models. The results in experimental models are related with
      the theoretical interaction studies of these ligands on the target proteins as 3D
      models in order to explore the biological effects of BCC in molecular detail.

PMID- 21861809
TI  - Epidermal growth factor receptor irreversible inhibitors: chemical exploration of
      the cysteine-trap portion.
AB  - Covalent EGFR irreversible inhibitors showed promising potential for the
      treatment of gefitinib-resistant tumors and for imaging purposes. They contain a
      cysteine-reactive portion forming a covalent bond with the protein. Irreversible
      kinase inhibitors have been advanced to clinical studies, mostly characterized by
      an acrylamide or butynamide warhead. However, the clinical usefulness of these
      compounds has been hampered by resistances, toxicity and pharmacokinetic
      problems. Investigation on the structure-activity and structure-reactivity
      relationships may provide useful information for compounds with improved
      selectivity and pharmacokinetic properties. This review focuses on the
      exploration of the cysteine-trap portions able to irreversibly inhibit EGFR and
      other erbB receptors.

PMID- 21861810
TI  - Recent advances in the field of 16-membered macrolide antibiotics.
AB  - The continuing emergence of bacterial resistance has provided an incentive for
      recent intensified research on macrolide antibiotics. Belonging to the macrolide
      family, 16-membered macrolides also experience a renewed interest in further
      exploration. The medicinal potential of 16-membered macrolides in search for new
      antibacterials stems from some advantages over 14-membered macrolides, such as
      gastrointestinal tolerability, structural flexibility, and lack of inducible
      resistance. Thus, compared with abundant articles on various 14-membered
      macrolide derivatives in the literature, this review will highlight some
      representative 16-membered macrolide antibiotics and their recently discovered
      analogs. Furthermore, the action and resistance mechanisms of 16-membered
      macrolide antibiotics will be elucidated as well to assist the drug design.

PMID- 21861812
TI  - Current inhibitors of checkpoint kinase 2.
AB  - Checkpoint kinase 2 is a serine/threonine protein which functions as an important
      transducer in apoptosis or DNA repair following activation by DNA damage.
      Inhibition of checkpoint kinase 2 is thought to sensitize p53-mutated or p53
      deficient cancerous cells but protect normal tissue following DNA-damage caused
      by ionizing radiation or chemotherapeutic agents. The development of checkpoint
      kinase inhibitors for the treatment of cancer has therefore been a major
      objective in drug discovery over the past decade. Several inhibitors have been co
      crystallized in the active site of checkpoint kinase 2 revealing important
      features of effective inhibitors. Some of these inhibitors have entered clinical
      trials in the last decade. This review describes and discusses the most recent
      inhibitors of checkpoint kinase 2 as reported in the literature, including an
      evaluation of biological activity.

PMID- 21861811
TI  - Most recent developments and modifications of 14-alkylamino and 14-alkoxy-4,5
      epoxymorphinan derivatives.
AB  - The 14-position of natural opiates (e.g. morphine) are unsubstituted, however
      synthetic approaches have uncovered that functionalizing position 14 gives rise
      to a wide range of diverse activities. This review focuses on SAR of the
      position, with the aim of aiding in the search for opioid analgesics with
      improved clinical profiles.

PMID- 21861813
TI  - Promoting adult hippocampal neurogenesis: a novel strategy for antidepressant
      drug screening.
AB  - Major depression is a common mood disorder that affects overall health;
      currently, almost all of the available antidepressants have the same core
      mechanisms of action through promotion of serotonin or noradrenaline function in
      the brain. The major limitation of today's antidepressants is that chronic
      treatment (3 - 6 weeks) is required before a therapeutic benefit is achieved.
      More effective and faster treatments for depression are needed. Adult
      neurogenesis is the birth of new neurons, which continues postnatally and into
      adulthood in the brains of multiple species, including humans. Recently, a large
      body of evidence gives rise to the hypothesis that the antidepressant effect and
      increases in adult hippocampal neurogenesis may be causally related. Multiple
      classes of antidepressants increase hippocampal neurogenesis in a chronic, but
      not acute, time course. This effect corresponds to the therapeutic time lag
      associated with current antidepressants. In addition, antidepressants are not
      effective in behavioral models of depression when hippocampal neurogenesis is
      prevented. This review examines the current understanding of adult neurogenesis
      and the evidence of the causal relationship between antidepressant effects and
      adult hippocampal neurogenesis. We also present our recent research findings,
      which support a promising strategy for enhancing adult hippocampal neurogenesis
      that might be a new approach for the development of novel antidepressants.

PMID- 21861814
TI  - Evaluation of anticonvulsants for possible use in neuropathic pain.
AB  - Neuropathic pain is a kind of pain related with functional abnormality of
      neurons. Despite large progress in pharmacotherapy, neuropathic pain is still
      considered an unmet need. Nowadays, there are few drugs registered for this
      condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and
      lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known
      antiepileptic drugs. Among the group of new antiepileptic drugs, which are
      addressed to 1% of human world population suffering from seizures, it turned out
      that 30% of the seizures resistant to pharmacotherapy has not enough market to
      justify the costs of drug development. Therefore, it is already a phenomenon that
      researchers turn their projects toward a larger market, related with possible
      similar mechanism. Anticonvulsant mechanism of action is in the first place among
      primary indications for drugs revealing potential analgesic activity. Therefore,
      many drug candidates for epilepsy, still in preclinical stage, are being
      evaluated for activity in neuropathic pain. This review is focusing on
      antiepileptic drugs, which are evaluated for their analgesic activity in major
      tests related with neuropathic pain. Relation between structure, mechanism of
      action and result in tests such as the Chung model (spinal nerve ligation SNL),
      the Bennett model (chronic constriction injury of sciatic nerve CCI) and other
      tests are considered. The first examples are carbamazepine, gabapentin, and
      lacosamide as drugs well established in epilepsy market as well as drug
      candidates such as valnoctamide, and other valproic acid derivatives, novel
      biphenyl pyrazole derivatives, etc. Moreover, clinical efficacy related with
      listed animal models has been discussed.

PMID- 21861816
TI  - New strategies in the discovery of novel non-camptothecin topoisomerase I
      inhibitors.
AB  - Topoisomerase I (Top1) represents an important target of active interest in
      developing novel anticancer agents. Camptothecin derivatives are the only class
      of clinically approved Top1 inhibitors and show potent efficacy in anticancer
      therapy. However, there are also several major limitations for them, such as poor
      chemical stability, drug resistance, long infusions and side effects. To overcome
      the drawbacks of the camptothecins, the discovery of non-camptothecin Top1
      inhibitors has recently emerged as a promising field to find better antitumor
      agents. Non-camptothecin Top1 inhibitors are expected to possess better chemical
      stability, different therapeutic activities and antitumor spectrum, improved
      pharmacokinetics and lower toxicity. This review focuses on various strategies
      that were used in the discovery of non-camptothecin Top1 inhibitors. In
      particular, the chemical scaffolds, structure-activity relationships and binding
      modes of the newly identified non-camptothecin Top1 inhibitors are discussed in
      detail.

PMID- 21861817
TI  - Evolving molecular mechanism-based strategies for control of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide.
      Unresectable or metastatic HCC has a poor prognosis, and systemic cytotoxic
      chemotherapy has failed to show a substantial benefit for patients with HCC.
      However, there has been increasing interest in developing novel molecularly
      targeted agents in HCC due to the accumulation of knowledge of cell signaling and
      molecular carcinogenesis. Furthermore, some of these agents have proven to be
      efficacious in other traditionally challenging carcinomas, such as renal cell
      carcinoma. Recently, a phase III, randomized, placebo-controlled trial
      demonstrated that sorafenib, an oral multikinase inhibitor of the vascular
      endothelial growth factor receptor and Ras kinase, improves overall survival (OS)
      in patients with advanced HCC. This seminal study described the first agent to
      improve OS in HCC and began a new era of molecule-targeted cancer therapies.
      Currently, many novel molecularly targeted agents are under evaluation in
      clinical trials. In this review, we comprehensively summarize the molecular
      pathogenesis, targets, and signal transduction pathways involved in HCC. We also
      detail the current status of molecularly targeted agents that are under clinical
      development in advanced HCC, including the mechanisms of action of these agents.

PMID- 21861815
TI  - Hypoxia inducible factor-1 as a target for neurodegenerative diseases.
AB  - Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor responsible for
      cellular and tissue adaption to low oxygen tension. HIF-1, a heterodimer
      consisting of a constitutively expressed beta subunit and an oxygen-regulated
      alpha subunit, regulates a series of genes that participate in angiogenesis, iron
      metabolism, glucose metabolism, and cell proliferation/survival. The activity of
      HIF-1 is controlled by post-translational modifications on different amino acid
      residues of its subunits, mainly the alpha subunit. Besides in ischemic stroke
      (see review [1]), emerging evidence has revealed that HIF-1 activity and
      expression of its down-stream genes, such as vascular endothelial growth factor
      and erythropoietin, are altered in a range of neurodegenerative diseases. At the
      same time, experimental and clinical evidence has demonstrated that regulating
      HIF-1 might ameliorate the cellular and tissue damage in the neurodegenerative
      diseases. These new findings suggest HIF-1 as a potential medicinal target for
      the neurodegenerative diseases. This review focuses on HIF-1alpha protein
      modifications and HIF-1's potential neuroprotective roles in Alzheimer's (AD),
      Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis
      (ALS).

PMID- 21861818
TI  - Targeting opioid and neurokinin-1 receptors to treat alcoholism.
AB  - Alcoholism is a multifarious and ongoing disease tightly related to the amount of
      alcohol ingested, the drinking pattern, the history of alcohol drinking and the
      individual features, such as some genetic traits. Worldwide alcohol is the
      necessary cause of approximately 60 diseases and causes circa 2.5 million deaths
      every year. Studies show that alcohol interacts with brain neurotransmission in a
      complex manner. Dopaminergic, GABAergic, serotonergic, cholinergic and
      glutamatergic systems are all key participants in the action of ethanol on the
      brain. Furthermore, several neuropeptides, such as endogenous opioid peptides,
      substance P, corticotropin-releasing hormone, or the appetite-regulating peptides
      (eg., neuropeptide Y, ghrelin or orexin) also play a role in alcohol drinking.
      Treatment of alcohol use disorders (AUD) is based on the application of combined
      approaches, including pharmacological intervention directed to different
      molecular targets. Results, however, are variable, not always satisfactory, and
      not applicable to all stages and pathologies or to all patients. New strategies
      focused on the control of neuropeptide performance in the brain are being
      explored and may be an advance in the therapy of alcoholism. The application of
      treatments ad personam represents a challenge that currently stimulates research
      in different realms, including epidemiology, psychology, chemistry, biochemistry,
      cell biology and pharmacology. In this review the potential value and application
      of ligands that modulate the function of opioid and neurokinin-1 receptors in
      alcoholism therapy is analyzed.

PMID- 21861819
TI  - Recent progress in medicinal investigations on trichosanthin and other ribosome
      inactivating proteins from the plant genus Trichosanthes.
AB  - Ribosome inactivating proteins (RIPs) are toxic RNA N-glycosidases that cleave an
      adenine-ribose glycosidic bond at position adenine(4324) with the conserved
      ricin/alpha-sarcin loop in the eukaryotic 28S ribosomal RNA. RIPs have captured
      the attention of botanists, biochemists, and drug discoverers, due to their
      diverse potent defensive activities, and inter alia, their antitumor and anti-HIV
      activities. Out of the 145 families of plants, Trichosanthes ranks among the top
      5 genera with a good potential of use for discovery of anticancer drugs.
      Trichosanthin (TCS) is a famous type I RIP purified from T. kirilowii that has
      been known for around 30 years. Based on the results of voluminous in vitro and
      in vivo investigations, TCS is considered a good candidate for the treatment of
      HIV/AIDS and neoplasms. Here we integrate recent progress of the research on the
      different medicinal activities of TCS. In addition to TCS, other promising RIPs
      from the same species (such as TAP29 and trichoanguin), and from the same genus
      Trichosanthes are included. This review presents a brief panorama of the studies
      on Trichosanthes RIPs. Regarding the debilitating nature of AIDS and different
      tumors, further understanding of these multifunctional proteins is worthwhile
      since it may help to open a novel therapeutic window for these stubborn diseases.

PMID- 21861820
TI  - Alzheimer's disease: emerging trends in small molecule therapies.
AB  - Alzheimer's disease (AD) is a highly complex and rapidly progressive
      neurodegenerative disorder characterized by the systemic collapse of cognitive
      function and formation of dense amyloid plaques and neurofibrillary tangles. AD
      pathology is derived from the cholinergic, amyloid and tau hypotheses,
      respectively. Current pharmacotherapy with known anti-cholinesterases, such as
      Aricept(r) and Exelon(r), only offer symptomatic relief without any disease
      modifying effects. It is now clear that in order to prevent the rapid progression
      of AD, new therapeutic treatments should target multiple AD pathways as opposed
      to the traditional "one drug, one target" approach. This review will focus on the
      recent advances in medicinal chemistry aimed at the development of small molecule
      therapies that target various AD pathological routes such as the cholinesterases
      (AChE and BuChE), amyloidogenic secretases (beta/gamma- secretase), amyloid-beta
      aggregation, tau phosphorylation and fibrillation and metal-ion redox/reactive
      oxygen species (ROS). Some notable ring templates will be discussed along with
      their structure-activity relationship (SAR) data and their multiple modes of
      action. These emerging trends signal a paradigm shift in anti-AD therapies aimed
      at the development of multifunctional small molecules as disease-modifying agents
      (DMAs).

PMID- 21861821
TI  - Monocyclic beta-lactams: new structures for new biological activities.
AB  - The azetidinone core-structure offers a unique approach to the design and
      synthesis of new derivatives with unique biological properties. During the last
      two decades researches convincingly demonstrated that the prospect of structural
      modifications of monocyclic beta-lactams with specific substituents is an
      effective procedure for the detection and improvement of important
      pharmacological effects different from antibacterial activity. As a matter of
      fact, new beta-lactam compounds demonstrated biological activity as inhibitors of
      a wide range of enzymes. This review reports the latest developments on
      monocyclic beta-lactam compounds activity as anticancer, antitubercular, HFAAH
      inhibitors, HDAC inhibitors, anti-inflammatory drugs (tryptase inhibitors),
      Cathepsin K inhibitors, and vasopressin inhibitors. We attempted to highlight the
      intertwined relationships between structural features and biological activities,
      by analysing groups anchored on the three positions of the azetidinone ring as
      sources of molecular diversity.

PMID- 21861822
TI  - New therapeutic strategy for mood disorders.
AB  - The development of new treatments for mood disorders, as anxiety and depression,
      is based on identification of neural substrates and the mechanisms underlying
      their etiology and pathophysiology. The heterogeneity of mood disorders indicates
      that its origin may lie in dysfunction of multiple brain regions (amygdala,
      nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex). The
      hippocampus of patients with depression show signs of atrophy and neuronal loss.
      This suggests the contribute of new neurons to the biology of mood disorders that
      is still under debate. The production of new neurons, referred to as
      neurogenesis, occurs throughout life in discrete brain areas such as the dentate
      gyrus (DG) of the hippocampus and the subventricular zone/olfactory bulb.
      Findings describing that neurogenesis process in DG is increased by
      antidepressants, like fluoxetine, and it is required for the behavioral effect of
      antidepressants, lead to a new strategy and drugs for the treatment of mood
      disorders. As many patients display poor response to therapy, research on
      depression and antidepressant drugs is necessary. In this regard, focusing on
      neurogenesis and neuroplasticity processes in experimental models is particularly
      interesting for the understanding of the pathophysiology of mood disorders and
      should define the role of adult-born neurons in hippocampal physiology. Different
      classes of drugs are currently prescribed for the treatment of mood disorders.
      Among them selective serotonin reuptake (SSRIs), monoamine oxidase inhibitors
      (MAOIs), specific norepinephrine reuptake inhibitors (SNRIs) and tricyclic acids
      (TCA) alleviate symptoms of mood disorders. Here we review different strategies
      that may be adopted for impairing mood disorders and that may be further
      developed for innovative therapeutic approaches.

PMID- 21861824
TI  - Human embryonic and induced pluripotent stem cells in cardiovascular drug
      discovery: patents and patented uses.
AB  - Human embryonic stem cells, hES, and the recently created human induced
      pluripotent stem cells, hiPS, have a multitude of uses in cardiovascular drug
      discovery with a significant patent coverage for most applications. The research
      involving hiPS and hES cells may be subdivided into two main areas: one utilizing
      undifferentiated cells, and the other using hES and hiPS for in vitro
      differentiation of mature cell types. Both areas are of use in basic discovery,
      high throughput screening, and toxicology research. A number of methods have been
      developed to differentiate stem cells to mature cardiac cell types and to obtain
      pure populations of cardiomyocytes. This review will discuss three major aspects
      of stem cell patent landscape: 1) patents pertaining to the basic methodology of
      obtaining hES and hiPS cells, 2) patents pertaining to the methods of hiPS and
      hES differentiation to cardiovascular cell types, and 3) patents concerned with
      the applied uses of differentiated cardiac cells.

PMID- 21861826
TI  - P2Y12 receptor antagonists in acute coronary syndrome: clinical implications of
      pharmacologic and pharmacogenetic differences.
AB  - Platelet activation and aggregation are key events in the pathophysiological
      process of thrombosis, and vascular occlusions. Antiplatelet therapy has proven
      to be crucial for managing patients with acute coronary syndromes, coronary
      artery disease and in patients undergoing percutaneous coronary interventions.
      However, residual platelet reactivity on antiplatelet treatment confers a five
      fold increased risk of major adverse cardiovascular events which indicates a need
      for more effective antiplatelet medications to address the substantial burden of
      cardiovascular disease. This article reviews the P2Y(12) receptor antagonists
      with regards to pharmacologic and pharmacogenetic differences and their clinical
      implications along with the discussion of recent patents.

PMID- 21861823
TI  - Differential innate immune responses to low or high dose oral SIV challenge in
      Rhesus macaques.
AB  - Mucosal transmission of HIV predominately occurs during sexual intercourse or
      breast-feeding and generally results in a successful infection from just one or
      few founder virions. Here we assessed the impact of viral inoculum size on both
      viral and immune events within two groups of Rhesus macaques that were non
      traumatically, orally inoculated with either multiple low (1000 to 4000 TCID(50))
      or high (100,000 TCID(50)) doses of SIV. In agreement with previous studies, more
      diverse SIV variants were observed in macaques following infection with high dose
      oral SIV compared to a low dose challenge. In peripheral blood cells, the immune
      gene transcript levels of CXCL9, IFNgamma, TNFalpha and IL10 remained similar to
      uninfected macaques. In contrast, OAS and CXCL10 were upregulated following SIV
      infection in both the high and low dosed macaques, with a more rapid kinetics
      (detectable by 7 days) following the high SIV dose challenge. In peripheral lymph
      nodes, an increase in CXCL10 was observed irrespective of viral dose while CXCL9
      and OAS were differentially regulated in the two SIV dosed groups. Magnetic bead
      sorting of CD3+, CD14+ and CD3- /CD14- cells from peripheral blood identified the
      increase in OAS expression primarily within CD14+ monocytes, whereas the CXCL10
      expression was primarily in CD3+ T cells. These findings provide insights into
      the impact of SIV challenge dose on viral and innate immune factors, which has
      the potential to inform future SIV/HIV vaccine efficacy trials in which
      vaccinated hosts have the potential to be infected with a range of viral
      challenge doses.

PMID- 21861827
TI  - Growing collateral arteries on demand.
AB  - Recent studies have significantly advanced our understanding of arteriogenesis,
      raising hope that therapies to increase collateral arterial formation may become
      important new tools in the treatment of ischemic disease. The most important
      initiating trigger for arteriogenesis is the marked increase in shear stress
      which is sensed by the endothelium and leads to characteristic changes.
      Intracellularly, it was shown that platelet endothelial cell adhesion molecule
      (PECAM-1) becomes tyrosine-phosphorylated in response to increased shear stress,
      suggesting a role as a possible mechanoreceptor for dynamic and continual
      monitoring of shear stress. The signal generated by PECAM-1 leads to the
      activation of the Rho pathway among others. More than 40 genes have been shown to
      have a shear stress responsive element. The Rho pathway is activated early and
      appears to be essential to the arteriogenic response as inhibiting it abolished
      the effect of fluid shear stress. Overexpression of a Rho pathway member, Actin
      binding Rho protein (Abra), led to a 60% increase in collateral perfusion over
      simple femoral artery occlusion. A patent for the Abra gene has been filed
      recently. It may be a harbinger of a future where collateral arteries grown on
      demand may become an effective treatment for ischemic vascular disease.

PMID- 21861828
TI  - Modifying cardiovascular risk factors: epidemiology and characteristics of
      hypertension-related disorders.

PMID- 21861829
TI  - Developments in imaging technologies related to hypertensive cardiovascular
      diseases.
AB  - This article reviews the current imaging techniques and the methodologies used to
      derive quantitative markers of hypertension in the cardiovascular system.
      Firstly, simple but effective methods to assess regional and global function of
      large arteries are discussed. After, the role of echocardiography and high
      resolution magnetic resonance imaging to assess geometric and mechanical indices
      of hypertension related cardiac diseases are summarized. In particular,
      quantitative indices of deformation and strain are derived from quantitative
      analysis of doppler tissue and tagged magnetic resonance images. Finally, the
      importance of high field magnetic resonance imaging to assess myocardial
      microcirculation is described.

PMID- 21861830
TI  - Ectopic fat storage, insulin resistance, and hypertension.
AB  - Obesity, insulin resistance, glucose intolerance/type 2 diabetes and hypertension
      are clustered in the metabolic syndrome representing critical risk factors for
      increased incidence cardio-cerebro-vascular diseases, kidney failure and cancer.
      Ectopic fat accumulation, i.e., accumulation in the mediastinum, liver and the
      abdomen, as well as generalized fat accumulation are associated with arterial
      hypertension, either systolic or diastolic. Several mechanisms including insulin
      resistance, sub-inflammatory state, increased Renin- Angiotensin-Aldosterone
      System (RAAS) system activity, oxidative stress, autonomic dysregulation as well
      as mechanical compression on the kidneys are all activated by obesity.
      Interestingly angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      (ATII) receptor blockers, while correcting arterial hypertension, also have a
      positive effect on glucose metabolism and diabetes prevention, in high risk
      patients. The implementation of dietary, medical and surgical strategies to
      prevent and treat obesity, are cornerstones for the primary prevention as well as
      treatment of arterial hypertension.

PMID- 21861831
TI  - Markers of arrhythmogenic risk in hypertensive subjects.
AB  - Hypertension is increasingly considered a strong and independent risk factor for
      supraventricular and ventricular arrhythmias. The presence and complexity of both
      supraventricular and ventricular arrhythmias influence morbidity, mortality, as
      well as the quality of life of patients. Diastolic dysfunction of the left
      ventricle, left atrial size and function, and left ventricular hypertrophy have
      been suggested as the foremost underlying risk factors for supraventricular and
      ventricular arrhythmias in hypertensive patients. In particular, the presence of
      hypertension is a risk for sudden death and this risk is higher in those with
      left ventricular hypertrophy. Moreover, arrhythmias in the hypertrophic heart are
      often facilitated and aggravated by electrolyte disturbances, sympatho-vagal
      unbalance, transient blood pressure peaks, and occurrence of myocardial
      ischaemia. Several noninvasive biohumoral, electrocardiographic and imaging
      parameters have been widely investigated to identify hypertensive patients at
      higher risk for the development of arrhythmias. These parameters include
      neurohormones, signal averaged analysis of P wave, QT interval dispersion, heart
      rate variability, ventricular late potentials and T wave morphology analysis, as
      well as echocardiographic and magnetic resonance indexes of atrial and
      ventricular shape and function. The aim of this review is to evaluate the
      relationship of high blood pressure with ventricular and supraventricular
      arrhythmias, to discuss the available biomarkers for arrhythmic risk assessment
      in hypertensive patients and the effects of a tailored tight blood pressure
      control on the occurrence of arrhythmias.

PMID- 21861832
TI  - Blood pressure and vascular alterations with growth in childhood.
AB  - The long preclinical phase of atherosclerosis involves the interaction of genetic
      and environmental factors that modulate the progression of disease from early
      life. A variety of noninvasive tests have been used to study the arterial
      phenotype of childhood, allowing identification of arterial alterations long
      before clinical symptoms of cardiovascular (CV) disease become apparent. These
      techniques have improved our understanding of the evolution of atherosclerosis,
      indentifying three major developmental factors which influence the future risk of
      CV disease in childhood: prenatal growth, early postnatal growth and childhood
      obesity. Specific changes in arterial properties and increased values of blood
      pressure are detectable in children with low birth weight, suggesting that
      intrauterine growth retardation could programme the future risk of CV disease.
      However, an accelerated growth rate in infancy and early childhood is often
      associated with low birth weight and with specific vascular alterations, making
      it difficult to distinguish the contribution of prenatal and postnatal growth
      patterns to later cardiovascular disease risk. Relationships between growth
      patterns and CV disease risk are further complicated by the link between rapid
      postnatal growth and later development of childhood overweight and obesity,
      conditions associated with early changes in vascular physiology and that
      potentially affect future CV outcome. This article aims to provide an overview of
      evidence in support of fetal programming and growth acceleration hypotheses for
      adult CV disease. Specific attention is given to obesity-related vascular
      alterations and their effects on future CV disease risk. We also summarise
      current non-invasive approaches to investigate the precursors and early
      development of CV disease, emphasising their potential applications in childhood.

PMID- 21861833
TI  - Vascular abnormalities in essential hypertension.
AB  - Arterial hypertension is a very common disease and an important risk factor for
      cardiovascular disease. Patients with arterial hypertension are characterized by
      functional and structural vascular abnormalities. Vascular endothelium plays a
      fundamental role in modulating vascular tone and structure. The physiological
      production of the relaxing factors including nitric oxide, prostacyclin and
      hyperpolarizing relaxing factors protects the vessel wall by antagonizing the
      first pathogenetic steps of atherosclerosis and thrombosis. Endothelial cells may
      also produce endothelium-derived contracting factors. The principal component of
      these contracting factors is endothelin-1, which promotes the growth of the
      smooth muscle cells and has a vasoconstrictive and blood pressure raising effect.
      Defective nitric oxide production is already detectable in normotensive offspring
      of hypertensive patients and young essential hypertensives. A dysfunctional
      endothelium due to reduced nitric oxide availability associated with an increased
      production of oxidative stress and vasoconstricting factors is considered as an
      early indicator of atherothrombotic damage and of cardiovascular events also in
      patients with arterial hypertension. Moreover, patients with arterial
      hypertension are also characterized by increased arterial stiffness. This
      parameter, known as a sign of cardiovascular risk since the 19th century, has
      been shown to be a predictor of adverse cardiovascular outcome and its
      measurement in hypertensive patients is suggested by the European guidelines for
      the diagnosis and treatment of hypertension.

PMID- 21861834
TI  - Cognitive decline as a consequence of essential hypertension.
AB  - Hypertension is a leading cardiovascular risk for cardiovascular morbidity and
      mortality. Age is the strongest risk factor for dementia and with the increasing
      life expectancy the number of patients living with dementia worldwide is
      estimated to progressively rise. A number of studies support an association
      between hypertension, particularly in midlife, and the development of cognitive
      disorders and dementia, including Alzheimer's disease. According to this,
      considering hypertension as a possible modifiable risk factor for the cognitive
      decline is of great clinical interest. Treatment of hypertension in midlife seems
      to promote considerable benefits with regard to cardiovascular outcomes.
      Longitudinal studies examining the possible benefit of anti-hypertensive
      treatments on cognitive decline have produced promising results. Nevertheless,
      the results from randomised controlled clinical trials on treatment of
      hypertension are not conclusive for the effect on cognitive decline and dementia.
      New randomized controlled trials are needed to definitively clarify clinical
      advantages and specifically elucidate the relationship between anti-hypertensive
      treatments and cognitive function or dementia.

PMID- 21861835
TI  - Hypertension in the elderly: an evidence-based review.
AB  - The progressive ageing of world population, and the increasing prevalence
      hypertension in elderly people are leading to the consideration that hypertension
      in the elderly is one of the main topic in hypertension treatment. Multiple
      mechanisms, including stiffening of large arteries, endothelial dysfunction,
      cardiac remodeling, autonomic dysregulation, renal aspects, contribute to the
      great prevalence of hypertension in the elderly and to increased cardiovascular
      morbidity and mortality. Treatment of hypertension can hardly put back older
      patients in a low risk category, especially if target organ damage is present.
      Nevertheless, blood pressure control can successfully prevent stroke, cognitive
      decline, coronary heart disease and heart failure, and reduce mortality in the
      elderly, and even in patients > 80 years, as recently demonstrated. Blood
      pressure should be lowered below 140/90 mmHg also in older patients. However the
      HYVET study suggests that a goal of 150/90 mmHg can be reasonable in patients
      aged 80 years or more. Drug treatment should be titrated with particular caution
      to adverse responses and excessive blood pressure lowering.

PMID- 21861836
TI  - Endothelial progenitor cells in prehypertension.
AB  - Blood pressure within prehypertensive levels confers higher cardiovascular risk.
      As prehypertension is also an intermediate stage for full hypertension, a
      precocious intervention with lifestyle changes or drugs is therefore appealing.
      Endothelial injury and dysfunction are thought to contribute to cardiovascular
      risk in prehypertension. Endothelial progenitor cell impairment has been linked
      to endothelial dysfunction, atherosclerotic disease progression and
      cardiovascular events. A potential mechanism contributing to the heightened
      cardiovascular risk in prehypertension may be linked to abnormalities in
      endothelial progenitor cell number and/or function. Aim of this review is to be
      up to date about the recent work on the correlation between endothelial
      progenitor cells and prehypertension and the possible prevention, treatment, and
      control of this pathology. The effect of an approach based on dietary
      intervention on both blood pressure and endothelial progenitor cells will be also
      shown.

PMID- 21861837
TI  - Smoking and hypertension: effects on clinical, biochemical and pathological
      variables due to isolated or combined action on cardiovascular system.
AB  - Changes in clinical, biochemical and pathological variables characterize
      cardiovascular damage from smoking and hypertension when it acts independently.
      However, combined action of these major risk factors increases the rate of
      cardiovascular events. Ischaemic heart disease with stable effort angina,
      myocardial infarction and post-infarction arrhythmias may affect cardiovascular
      system because of smoking exposure. Among cerebrovascular disease, there is
      evidence that stroke would be related primarily to active smoking. Isolated
      hypertension plays significantly major action to cause cerebrovascular disease
      including stroke, recurrent stoke and transient ischaemic attack. Among cardiac
      events, heart failure is, often, the end-point of hypertensive disease, even if
      manifestations of ischaemic heart disease similar to those caused by smoking may
      be increased in rate. Combined action of smoking and hypertension usually
      increases the rate of cardiovascular complications and leads to a progression of
      atherosclerosis with narrowing and plaque primarily at the the level of coronary,
      carotid and cerebrovascular arteries. A pattern specific of both active and
      passive smoking exposure, but not hypertension, is the thromboangiitis obliterans
      that dramatically worsens in continuing smokers while it can be improved by
      stopping smoking.

PMID- 21861838
TI  - Susceptibility genes in hypertension.
AB  - Hypertension is a complex, multifactorial disease; genetic factors represent one
      third to half of the inter-individual variability of blood pressure values. Among
      the causes of secondary hypertension are a group of disorders with a Mendelian
      inheritance pattern. Recent advances in molecular biology have revealed the
      pathogenesis of hypertension in many of these conditions. Remarkably, the
      mechanism in every case has proved to be upregulation of sodium Na reabsorption
      in the distal nephron, with accompanying expansion of extracellular volume. On
      the contrary in the essential hypertension the underlying pathogenetic mechanism
      is more complex because of interplay between several 'risk' genes and
      environmental factors. It is assumed that blood pressure is under the control of
      a large number of genes each of which has only relatively mild effects. It has
      therefore been difficult to discover the genes that contribute to blood pressure
      variation using traditional approaches including candidate gene studies and
      linkage studies. Recent development of genotyping technology made large scale
      genome-wide association studies possible. This approach and the study of
      monogenic forms of hypertension has led to the discovery of novel and robust
      candidate genes for human essential hypertension, many of which require
      functional analysis in experimental models. This review summarizes the current
      findings for candidate genes associated with blood pressure and focuses on recent
      advances and future potential of pharmacogenetics of hypertension, with the
      intent to clarify what amount of these investments in basic science research will
      be delivered into benefits to patients.

PMID- 21861839
TI  - Epidemiology and costs of hypertension-related disorders.
AB  - Epidemiological surveys demonstrate undoubtedly that cardiovascular disorders
      caused or associated with hypertension are at a high risk of non-fatal or fatal
      events and occurring with a great rate. Ischaemic heart disease with effort
      angina and myocardial infarction, often unrecognized myocardial infarction,
      stroke and transient ischaemic attack may be observed more frequently than other
      cardiovascular disorders in hypertensive patients. Large-scale trials do not
      support the hypothesis that effective benefits are reached by current non
      pharmacological or pharmacological prevention which need enormous costs to public
      health. Lowering blood pressure is the main target to reach in an attempt to
      reduce cardiovascular complications in hypertensive patients. Therefore, the
      costs-benefit ratio, which estimates public health costs, needs yet marked
      improvement since the public health expenses are heaviest with results that do
      not support the economic effort. Statistically, quantitative measures to modify
      the current regimen need to better evaluate both public health costs and reached
      benefits.

PMID- 21861840
TI  - Active-targeted nanotherapy strategies for prostate cancer.
AB  - Castration-resistant prostate cancer remains incurable and a major cause of
      mortality worldwide. The absence of effective therapeutic approaches for advanced
      prostate cancer has led to an intensive search for novel treatments. Emerging
      nanomedical approaches have shown promising results, in vitro and in vivo, in
      improving drug distribution and bioavailability, tumor penetration and in
      limiting toxicity. Nanoscaled carriers bearing finely controlled size and surface
      properties such as liposomes, dendrimers and nanoparticles have been developed
      for successful passive and active tumortargeting. Enhanced pharmacokinetics of
      nanotherapeutics, through improved target delivery and prolonged tissue halflife
      provides optimal drug delivery that is tumor-specific. Tumor-targeting may be
      improved through ligand directed delivery systems binding to tumor-specific
      surface receptors improving cellular uptake through receptor-mediated
      endocytosis. Recently published data have provided pre-clinical evidence showing
      the potential of active-targeted nanotherapeutics in prostate cancer therapy;
      unfortunately, only a few of these therapies have translated into early phase
      clinical trials development. Hence, progress of active-targeted nanotherapy
      improving efficiency of site-specific drug delivery is a critical challenge in
      future clinical treatment of prostate cancer. Exploring specific prostate cell
      surface antigens or receptor overexpression may elaborate promising strategies
      for future therapeutic design. This review presents an overview of some new
      strategies for prostate cancer active-targeting nanotherapeutics.

PMID- 21861841
TI  - H+-myo-inositol transporter SLC2A13 as a potential marker for cancer stem cells
      in an oral squamous cell carcinoma.
AB  - Cancer Stem Cells (CSCs) from tumors of different phenotypes possess a marked
      capacity for proliferation, self-renewal, and differentiation. They also play a
      critical role in cancer recurrence. Although CSC has been regarded as a new
      target for cancer therapy, the fundamental questions in the CSC study have not
      been resolved mainly due to the lack of proper CSC markers. To find new CSC
      markers for oral squamous cell carcinoma (OSCC), we cultured the primary tumor
      cells from OSCC patients the regular culture condition and the sphere-forming
      culture condition to enrich primary tumor cells and potential CSCs. We compared
      gene expression profiles between sphere-forming and non-forming cells, thus
      identifying that 23 membrane protein-coding genes were over-expressed in the
      sphere-forming cells. Among them, 8 belonged to the solute carrier (SLC) protein
      family. H+-myo-inositol transporter SLC2A13 and monocarbohydrate transporter
      SLC16A6 genes that were consistently increased in the sphere-forming cells in the
      primary cultures of OSCC samples. Confocal microscopy revealed that SLC2A13
      expressing cells were embedded in the limited areas of tumor tissue as a cluster,
      while SLC16A6 was uniformly detected in hyperplastic epithelium. Moreover,
      SLC2A13 an expression was induced in human breast adenocarcinoma MCF7 cells after
      serum starvation. Taken together, our results suggest that SLC2A13 can be a
      potential markers for CSC in various tumors.

PMID- 21861842
TI  - The phosphoinositide 3-kinase signaling pathway as a therapeutic target in grade
      IV brain tumors.
AB  - Brain tumors comprise a wide variety of neoplasia classified according to their
      cellular origin and their morphological and histological characteristics. The
      transformed phenotype of brain tumor cells has been extensively studied in the
      past years, achieving a significant progress in our understanding of the
      molecular pathways leading to tumorigenesis. It has been reported that the
      phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is frequently altered in
      grade IV brain tumors resulting in uncontrolled cell growth, survival,
      proliferation, angiogenesis, and migration. This aberrant activation can be
      explained by oncogenic mutations in key components of the pathway or through
      abnormalities in its regulation. These alterations include overexpression and
      mutations of receptor tyrosine kinases (RTKs), mutations and deletions of the
      phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor
      gene, encoding a lipid kinase that directly antagonized PI3K activity, and
      alterations in Ras signaling. Due to promising results of preclinical studies
      investigating the PI3K/AKT pathway in grade IV brain tumors like glioblastoma and
      medulloblastoma, the components of this pathway have emerged as promising
      therapeutic targets to treat these malignant brain tumors. Although an arsenal of
      small molecule inhibitors that target specific components of this signaling
      pathway is being developed, its successful application in the clinics remains a
      challenge. In this article we will review the molecular basis of the PI3K/AKT
      signaling pathway in malignant brain tumors, mainly focusing on glioblastoma and
      medulloblastoma, and we will further discuss the current status and potential of
      molecular targeted therapies.

PMID- 21861843
TI  - A higher body temperature is associated with haemorrhagic transformation in
      patients with acute stroke untreated with recombinant tissue-type plasminogen
      activator (rtPA).
AB  - Higher body temperature is a prognostic factor of poor outcome in acute stroke.
      Our aim was to study the relationship between body temperature, HT (haemorrhagic
      transformation) and biomarkers of BBB (blood-brain barrier) damage in patients
      with acute ischaemic stroke untreated with rtPA (recombinant tissue-type
      plasminogen activator). We studied 229 patients with ischaemic stroke <12 h from
      symptom onset. Body temperature was determined at admission and every 6 h during
      the first 3 days. HT was evaluated according to ECASS II (second European Co
      operative Acute Stroke Study) criteria in a multimodal MRI (magnetic resonance
      imaging) at 72 h. We found that 55 patients (34.1%) showed HT. HT was associated
      with cardioembolic stroke (64.2% against 23.0%; P<0.0001), higher body
      temperature during the first 24 h (36.9 degrees C compared with 36.5 degrees C;
      P<0.0001), more severe stroke [NIHSS (National Institutes of Health Stroke Scale)
      score, 14 (9-20) against 10 (7-15); P=0.002], and greater DWI (diffusion-weighted
      imaging) lesion volume at admission (23.2 cc compared with 13.2 cc; P<0.0001).
      Plasma MMP-9 (matrix metalloproteinase 9) (187.3 ng/ml compared with 44.2 ng/ml;
      P<0.0001) and cFn (cellular fibronectin) levels (16.3 MUg/ml compared with 7.1
      MUg/ml; P=0.001) were higher in patients with HT. Body temperature within the
      first 24 h was independently associated with HT {OR (odds ratio), 7.3 [95% CI
      (confidence interval), 2.4-22.6]; P<0.0001} after adjustment for cardioembolic
      stroke subtype, baseline NIHSS score and DWI lesion volume. This effect remained
      unchanged after controlling for MMP-9 and cFn. In conclusion, high body
      temperature within the first 24 h after ischaemic stroke is a risk factor for HT
      in patients untreated with rtPA. This effect is independent of some biological
      signatures of BBB damage.

PMID- 21861844
TI  - Revealing the structural origin of the redox-Bohr effect: the first solution
      structure of a cytochrome from Geobacter sulfurreducens.
AB  - Gs (Geobacter sulfurreducens) can transfer electrons to the exterior of its
      cells, a property that makes it a preferential candidate for the development of
      biotechnological applications. Its genome encodes over 100 cytochromes and,
      despite their abundance and key functional roles, to date there is no structural
      information for these proteins in solution. The trihaem cytochrome PpcA might
      have a crucial role in the conversion of electronic energy into protonmotive
      force, a fundamental step for ATP synthesis in the presence of extracellular
      electron acceptors. In the present study, 15N-labelled PpcA was produced and NMR
      spectroscopy was used to determine its solution structure in the fully reduced
      state, its backbone dynamics and the pH-dependent conformational changes. The
      structure obtained is well defined, with an average pairwise rmsd (root mean
      square deviation) of 0.25 A (1 A=0.1 nm) for the backbone atoms and 0.99 A for
      all heavy atoms, and constitutes the first solution structure of a Gs cytochrome.
      The redox-Bohr centre responsible for controlling the electron/proton transfer
      was identified, as well as the putative interacting regions between PpcA and its
      redox partners. The solution structure of PpcA will constitute the foundation for
      studies aimed at mapping out in detail these interacting regions.

PMID- 21861846
TI  - Apoptosis by aloe-emodin is mediated through down-regulation of calpain-2 and
      ubiquitin-protein ligase E3A in human hepatoma Huh-7 cells.
AB  - Natural flavonoids are associated with anti-proliferation of cancer growth.
      However, the antioxidant and anti-proliferation effects of AE (aloe-emodin) have
      not been well studied. We have investigated how AE affects the proliferation of
      hepatic hepatocellular carcinoma cells and exerts an anti-cancer effect. The
      cytotoxic effect of AE was demonstrated using an MTT [3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and Huh-7 cells were inhibited by
      AE treatment in both dose- and time-dependent manners. The IC(50) level of AE was
      ~75 MUM. AE also has anti-proliferative effects via induction of DNA damage and
      apoptosis. 2-DE (two-dimensional electrophoresis) revealed that several proteins
      were related to the anti-cancer effects of AE. CAPN2 (calpain-2) and UBE3A
      (ubiquitin-protein ligase E3A), which are associated with the apoptosis
      signalling pathway, were verified by Western blotting. AE exhibited potent anti
      proliferative effects on Huh-7 cells via down-regulation of CAPN2 and UBE3A. The
      findings support the possibility of AE being a chemopreventative agent.

PMID- 21861845
TI  - Effect of angiotensin receptor blockade on insulin sensitivity and endothelial
      function in abdominally obese hypertensive patients with impaired fasting
      glucose.
AB  - AngII (angiotensin II) may contribute to cardiovascular risk in obesity via
      adverse effects on insulin sensitivity and endothelial function. In the present
      study, we examined the effects of ARB (angiotensin receptor blocker) therapy
      (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53
      subjects with stage I hypertension, abdominal obesity and impaired fasting
      glucose. The study design was a randomized double-blinded parallel design placebo
      controlled multi-centre trial of 8 weeks duration. We used the hyperinsulinaemic
      euglycaemic clamp technique to measure insulin sensitivity (expressed as the
      'M/I' value) and RH-PAT (reactive hyperaemia-peripheral arterial tonometry) to
      measure endothelial function. Additional measures included HOMA (homoeostasis
      model assessment)-B, an index of pancreatic beta-cell function, and markers of
      inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F2
      isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre
      treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9)
      pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did
      improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did
      not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7)
      post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment
      and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation
      and oxidative stress were not significantly changed by ARB therapy. In
      conclusion, ARB therapy did not alter peripheral insulin sensitivity or
      endothelial function in this cohort of patients with essential hypertension,
      abdominal obesity and impaired fasting glucose, but did improve pancreatic beta
      cell function.

PMID- 21861847
TI  - Are diagnostic and public health bacteriology ready to become branches of genomic
      medicine?
AB  - : Diagnostic medical bacteriology is a conservative discipline. When busy house
      officers scribble 'M, C & S' on a form, they are requesting two techniques -
      microscopy and culture of microorganisms - that date back to the late 17th and
      late 19th century, respectively. The third technique - antibiotic susceptibility
      testing - has changed little in a half a century. Relatively few front-line
      diagnostic bacteriology laboratories have embraced molecular methods; on my own
      campus, the hospital's medical microbiology department does not even possess a
      thermal cycler!And yet in the research arena, genome sequencing has transformed
      almost every corner of the biomedical sciences, including the study of bacterial
      pathogens Furthermore, over the past 5 years, high-throughput (or 'next
      generation') sequencing technologies have delivered a step change in our ability
      to sequence microbial genomes 1. Since arriving in the market place, these
      technologies have experienced sustained technical improvement, which, twinned
      with lively competition between alternative platforms, has placed sequencing in a
      state of 'permanent revolution'.At last, it seems that genomics has come up with
      a game-changer, a killer app, a disruptive technology that even those long wedded
      to the Gram stain and the agar plate can no longer ignore. Does this mean we are
      on the brink of a revolution in diagnostic and public health microbiology, in
      which high-throughput sequencing usurps the traditional 'M, C & S', or will the
      discipline's innate conservatism stand firm for decades to come?

PMID- 21861848
TI  - Repeated phenotypic changes highlight molecular targets of convergent evolution.
AB  - How predictable is evolution at the molecular level? An example of repeated
      evolution in rice and Brassica illustrates how selection might preferentially
      target certain genes and mutations.

PMID- 21861850
TI  - PPAR action in insulin resistance unraveled by metabolomics: potential clinical
      implications.
AB  - Metabolomic analysis will provide the next large set of clues to further our
      understanding of human health and disease. A recent study has elucidated the
      significant differences in the metabolomes of adipocytes, serum and an adipocyte
      cell line after activation of two nuclear receptors, peroxisome proliferator
      activated receptor beta/delta (PPARbeta/delta) and PPARgamma. These findings hold
      great promise for explaining fundamental differences in the mechanisms of PPAR
      agonists and for identifying targets for the treatment of diabetes.See related
      research article: http://genomebiology.com/2011/12/8/R75.

PMID- 21861849
TI  - Genetics and genomics of radiotherapy toxicity: towards prediction.
AB  - Radiotherapy is involved in many curative treatments of cancer; millions of
      survivors live with the consequences of treatment, and toxicity in a minority
      limits the radiation doses that can be safely prescribed to the majority.
      Radiogenomics is the whole genome application of radiogenetics, which studies the
      influence of genetic variation on radiation response. Work in the area focuses on
      uncovering the underlying genetic causes of individual variation in sensitivity
      to radiation, which is important for effective, safe treatment. In this review,
      we highlight recent advances in radiotherapy and discuss results from four genome
      wide studies of radiotoxicity.

PMID- 21861851
TI  - Computational biology: plus c'est la meme chose, plus ca change.
AB  - A report on the joint 19th Annual International Conference on Intelligent Systems
      for Molecular Biology (ISMB)/10th Annual European Conference on Computational
      Biology (ECCB) meetings and the 7th International Society for Computational
      Biology Student Council Symposium, Vienna, Austria, 15-19 July 2011.

PMID- 21861852
TI  - Sequencing skippy: the genome sequence of an Australian kangaroo, Macropus
      eugenii.
AB  - Sequencing of the tammar wallaby (Macropus eugenii) reveals insights into genome
      evolution, and mammalian reproduction and development.

PMID- 21861853
TI  - Estrogen receptor degradation: a CUE for endocrine resistance?
AB  - Despite the undoubted success of adjuvant endocrine therapies that target the
      estrogen receptor pathway, not all women with estrogen receptor-positive breast
      cancer respond to these therapies, and many who initially respond will
      subsequently relapse. Deregulation of various aspects of estrogen receptor
      signaling has been highlighted as a mechanism of resistance and as a basis for
      alternative therapeutic approaches. However, a recent publication refocuses
      attention on the estrogen receptor itself by showing that the ubiquitin-binding
      CUE domain-containing protein 2 is a regulator of estrogen receptor protein
      degradation and a marker of endocrine resistance in breast cancer.

PMID- 21861854
TI  - Response to 'Pain persists in DAS28 rheumatoid arthritis remission but not in
      ACR/EULAR remission: a longitudinal observational study'.

PMID- 21861855
TI  - Globalization of Alzheimer's disease clinical trials.
AB  - Alzheimer's disease (AD) therapies are increasingly being tested in global
      clinical trials. A search of ClincalTrials.gov revealed that of 269 currently
      active trials, 28% are currently being conducted in the United States; the
      majority of trials and the majority of trial sites are ex-US. The US has the
      largest number of trial sites of any single country; cumulatively, nearly half of
      all sites are outside the US. The US conducts more trials in all phases of drug
      development but has a greater proportion of phase 3 trials. The increasing
      importance of global participants in clinical trials emphasizes the importance of
      considering the ethnic and international factors that may influence trial
      outcome. The International Conference on Harmonization guidelines divide ethnic
      factors that may affect drug development into intrinsic and extrinsic influences.
      These include language, cultural factors, educational levels, the general level
      of health and standard of care, as well as nutrition and diet. Ethnic influences
      on pharmacokinetics are known for some metabolic pathways. The biology of AD may
      also differ among the world's populations. The frequency of the apolipoprotein e4
      allele, a major risk factor for AD, differs internationally. Genetic variations
      might also affect inflammatory, excitotoxic, and oxidative components of AD.
      Diagnostic standards and experience vary from country to country. Levels of
      practitioner training and experience, diagnostic approaches to AD, and attitudes
      regarding aging and AD may differ. Experience and sophistication with regard to
      clinical trial conduct also vary within and between countries. Experience with
      conducting the necessary examinations, as well as the linguistic and cultural
      validity of instrument translations, may affect trial outcomes. Operational and
      regulatory aspects of clinical trials vary and provide important barriers to
      seamless conduct of multiregional clinical trials. Collection and testing of
      biological samples, continuous provision of drug substance, and protection of the
      integrity of supply lines may be difficult in some international circumstances.
      Attention to these potential influences on clinical trials will determine the
      success of global drug development programs and the utility of global trials for
      developing new AD therapeutics.

PMID- 21861856
TI  - A new weapon against an old target.
AB  - High expression of folate receptors is characteristic for the effector cell
      population of synovial macrophages in synovial inflammation. A new drug
      conjugate, EC0746, targets the folate inhibitor aminopterin to folate receptors.
      In vitro studies show that this conjugate acts antiproliferatively and inhibits
      cytokine production by macrophage cell lines. Moreover, it shows strong anti
      arthritic effects in the rat model of adjuvant-induced arthritis in vivo.
      Toxicity of aminopterin was reduced 40-fold by using equimolar doses of the drug
      conjugate. In conclusion, this new treatment approach has the potential to
      further improve the most successful principle of folate inhibition in the
      treatment of arthritis.

PMID- 21861857
TI  - Doing the dirty work: progress in the search for a reliable protocol for
      cardiomyogenesis.
AB  - Cardiomyocytes generated from pluripotent stem cells have the potential to
      facilitate our understanding of cardiac diseases and help in their treatment.
      However, realizing the full potential of this technology is limited by the
      field's inability to efficiently and reliably differentiate pluripotent stem
      cells into cardiomyocytes. But now, due to a massive undertaking by Burridge and
      colleagues in a recent issue of PLOS One, we are one step closer to the reliable
      creation of cardiomyocytes. By systematically addressing 45 different variables,
      Burridge and colleagues were able to develop a protocol that consistently
      produced cardiomyocytes independent of the cell source. However, work still needs
      to be done to increase the efficiency and definitively determine the maturity of
      the myocytes generated through such a protocol.

PMID- 21861858
TI  - Mesenchymal stem cell effects on T-cell effector pathways.
AB  - Mesenchymal stem (stromal) cells (MSCs) are rare, multipotent progenitor cells
      that can be isolated and expanded from bone marrow and other tissues. Strikingly,
      MSCs modulate the functions of immune cells, including T cells, B cells, natural
      killer cells, monocyte/macrophages, dendritic cells, and neutrophils. T cells,
      activated to perform a range of different effector functions, are the primary
      mediators of many autoimmune and inflammatory diseases as well as of transplant
      rejection and graft-versus-host disease. Well-defined T-cell effector phenotypes
      include the CD4+ (T helper cell) subsets Th1, Th2, and Th17 cells and cytotoxic T
      lymphocytes derived from antigen-specific activation of naive CD8+ precursors. In
      addition, naturally occurring and induced regulatory T cells (Treg) represent
      CD4+ and CD8+ T-cell phenotypes that potently suppress effector T cells to
      prevent autoimmunity, maintain self-tolerance, and limit inflammatory tissue
      injury. Many immune-mediated diseases entail an imbalance between Treg and
      effector T cells of one or more phenotypes. MSCs broadly suppress T-cell
      activation and proliferation in vitro via a plethora of soluble and cell contact
      dependent mediators. These mediators may act directly upon T cells or indirectly
      via modulation of antigen-presenting cells and other accessory cells. MSC
      administration has also been shown to be variably associated with beneficial
      effects in autoimmune and transplant models as well as in several human clinical
      trials. In a small number of studies, however, MSC administration has been found
      to aggravate T cell-mediated tissue injury. The multiple effects of MSCs on
      cellular immunity may reflect their diverse influences on the different T-cell
      effector subpopulations and their capacity to specifically protect or induce Treg
      populations. In this review, we focus on findings from the recent literature in
      which specific modulatory effects of MSCs on one or more individual effector T
      cell subsets and Treg phenotypes have been examined in vitro, in relevant animal
      models of in vivo immunological disease, and in human subjects. We conclude that
      MSCs have the potential to directly or indirectly inhibit disease-associated Th1,
      Th2, and Th17 cells as well as cytotoxic T lymphocytes but that many key
      questions regarding the potency, specificity, mechanistic basis, and predictable
      therapeutic value of these modulatory effects remain unanswered.

PMID- 21861859
TI  - Green tea: a new option for the prevention or control of osteoarthritis.
AB  - IL-1beta is a major cytokine driving the inflammatory processes leading to the
      pathophysiology of osteoarthritis and other inflammatory diseases. Blockade of IL
      1beta activity using substances such as the naturally occurring IL-1 receptor
      antagonist or anti-IL-1beta monoclonal antibody are currently being used or
      tested as therapy. However, such treatments are ineffective in osteoarthritis. In
      a recent study, epigallocatechin-3-gallate, a green tea polyphenol, was found to
      be effective in reducing IL-1beta-induced inflammatory cytokines, TNFalpha, IL-6,
      granulocyte-macrophage colony-stimulating factor and several chemokines from
      human chondrocytes. The use of green tea polyphenols may be beneficial as a
      therapeutic addition to biologics that control IL-1beta activity by increasing
      effectiveness and/or reducing dosage.

PMID- 21861860
TI  - Giant cell arteritis: immune and vascular aging as disease risk factors.
AB  - Susceptibility for giant cell arteritis increases with chronological age, in
      parallel with age-related restructuring of the immune system and age-induced
      remodeling of the vascular wall. Immunosenescence results in shrinkage of the
      naive T-cell pool, contraction of T-cell diversity, and impairment of innate
      immunity. Aging of immunocompetent cells forces the host to take alternative
      routes for protective immunity and confers risk for pathogenic immunity that
      causes chronic inflammatory tissue damage. Dwindling immunocompetence is
      particularly relevant as the aging host is forced to cope with an ever growing
      infectious load. Immunosenescence coincides with vascular aging during which the
      arterial wall undergoes dramatic structural changes and medium and large arteries
      lose their pliability and elasticity. On the molecular level, elastic fibers
      deteriorate and matrix proteins accumulate biochemical modifications. Thus, the
      aging process impacts the two major biologic systems that liaise to promote giant
      cell arteritis; the immune system and the vessel wall niche.

PMID- 21861861
TI  - Negative regulation of osteoclastogenesis and bone resorption by cytokines and
      transcriptional repressors.
AB  - Bone remodeling in physiological and pathological conditions represents a balance
      between bone resorption mediated by osteoclasts and bone formation by
      osteoblasts. Bone resorption is tightly and dynamically regulated by multiple
      mediators, including cytokines that act directly on osteoclasts and their
      precursors, or indirectly by modulating osteoblast lineage cells that in turn
      regulate osteoclast differentiation. The critical role of cytokines in inducing
      and promoting osteoclast differentiation, function and survival is covered by the
      accompanying review by Zwerina and colleagues. Recently, it has become clear that
      negative regulation of osteoclastogenesis and bone resorption by inflammatory
      factors and cytokines, downstream signaling pathways, and a newly described
      network of transcriptional repressors plays a key role in bone homeostasis by
      fine tuning bone remodeling and restraining excessive bone resorption in
      inflammatory settings. In this review we discuss negative regulators of
      osteoclastogenesis and mechanisms by which these factors suppress bone
      resorption.

PMID- 21861863
TI  - A novel use for novel acute kidney injury biomarkers: fenoldopam's effect on
      neutrophil gelatinase-associated lipocalin and cystatin C.
AB  - Substantial basic and translational research has been directed to detect earlier
      and more sensitive acute kidney injury (AKI) biomarkers over the past decade.
      Much of the seminal AKI biomarker validation research has been performed in
      children undergoing cardiopulmonary bypass since they represent an ideal clinical
      model for AKI biomarker study: the timing of the injury is known and children do
      not have many of the co-morbidities seen in adult patient populations, which can
      confound the clinical situation. Ricci and colleagues report the results of their
      study using two novel urinary AKI biomarkers, neutrophil gelatinase-associated
      lipocalin (NGAL) and cystatin C--not to predict AKI, but to define it--in a
      randomized trial of intraoperative fenoldopam to prevent AKI. They demonstrate
      that fenoldopam administration led to decreased postoperative urine NGAL and
      urine cystatin C concentrations, suggesting a renoprotective effect. Given the
      high sensitivity of NGAL for AKI post cardiopulmonary bypass, this study provides
      a model to use novel AKI biomarkers in a novel manner.

PMID- 21861862
TI  - Positive regulators of osteoclastogenesis and bone resorption in rheumatoid
      arthritis.
AB  - Bone destruction is a frequent and clinically serious event in patients with
      rheumatoid arthritis (RA). Local joint destruction can cause joint instability
      and often necessitates reconstructive or replacement surgery. Moreover,
      inflammation-induced systemic bone loss is associated with an increased fracture
      risk. Bone resorption is a well-controlled process that is dependent on the
      differentiation of monocytes to bone-resorbing osteoclasts. Infiltrating as well
      as resident synovial cells, such as T cells, monocytes and synovial fibroblasts,
      have been identified as sources of osteoclast differentiation signals in RA
      patients. Pro-inflammatory cytokines are amongst the most important mechanisms
      driving this process. In particular, macrophage colony-stimulating factor, RANKL,
      TNF, IL-1 and IL-17 may play dominant roles in the pathogenesis of arthritis
      associated bone loss. These cytokines activate different intracellular pathways
      to initiate osteoclast differentiation. Thus, over the past years several
      promising targets for the treatment of arthritic bone destruction have been
      defined.

PMID- 21861864
TI  - When to start dialysis in patients with acute kidney injury? When semantics and
      logic become entangled with expectations and beliefs.
AB  - Earlier initiation of dialysis may have a beneficial impact on survival of
      critically ill patients with acute kidney injury (AKI). A retrospective analysis
      in the previous issue of Critical Care showed that early initiation of renal
      replacement therapy (RRT), as defined by RIFLE criteria, was not associated with
      a reduction in hospital mortality. The retrospective character of many studies
      describing the results of early RRT initiation and the validity of RIFLE criteria
      to determine the need for dialysis can be questioned, in particular when urinary
      output is not considered. Initiating dialysis in AKI should be based on clinical
      criteria and not on serum creatinine or another serum/urine-based biomarker.

PMID- 21861865
TI  - Appropriate antibiotic dosing in severe sepsis and acute renal failure: factors
      to consider.
AB  - Severe sepsis and septic shock cause considerable morbidity and mortality. Early
      appropriate empiric broad-spectrum antibiotics and advanced resuscitation therapy
      are the cornerstones of treatment for these conditions. In prescribing an
      antibiotic regimen in septic patients with acute renal failure treated with
      continuous renal replacement therapy, several factors should be considered:
      pharmacokinetics, weight, residual renal function, hepatic function, mode of
      renal replacement therapy (membrane and surface area, sieving coefficient,
      effluent and dialysate rate, and blood flow rate), severity of illness,
      microorganism, minimum inhibitory concentration, and others. Studies that
      determine the serum antibiotic concentrations are very useful in establishing the
      correct dosage in critical patients.

PMID- 21861866
TI  - Lymphotoxin alpha revisited: general features and implications in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting synovial
      joints. Therapies blocking tumor necrosis factor-alpha (TNFalpha) are now
      routinely used in the management of RA. However, a significant number of patients
      with RA do not respond or develop resistance to anti-TNF therapies, and the
      participation of other cytokines in RA pathogenesis has been reported as well.
      Lymphotoxin alpha (LTalpha) is the closest homolog to TNFalpha and has been
      implicated in inflammation and autoimmunity since its original description in
      1968. In spite of that, little is known about the role of LTalpha in RA or the
      potential of blocking this cytokine as an alternative therapeutic approach. In
      this review, we aim to summarize the general features of LTalpha and what is
      currently known about its participation in RA.

PMID- 21861867
TI  - Are we ready for therapeutic drug monitoring of biologic therapeutics?
AB  - In the previous issue of Arthritis Research & Therapy, Ducourau and colleagues
      report that they retrospectively detected anti-infliximab antibodies in 21% of
      patients with rheumatic diseases. Patients with anti-infliximab antibodies had
      lower serum drug concentrations. These findings contribute to the existing
      evidence of immunogenicity of biologicals and its clinical relevance. We argue
      for therapeutic drug monitoring to optimize treatment response.

PMID- 21861868
TI  - Promise of periodontal ligament stem cells in regeneration of periodontium.
AB  - A great number of patients around the world experience tooth loss that is
      attributed to irretrievable damage of the periodontium caused by deep caries,
      severe periodontal diseases or irreversible trauma. The periodontium is a complex
      tissue composed mainly of two soft tissues and two hard tissues; the former
      includes the periodontal ligament (PDL) tissue and gingival tissue, and the
      latter includes alveolar bone and cementum covering the tooth root. Tissue
      engineering techniques are therefore required for regeneration of these tissues.
      In particular, PDL is a dynamic connective tissue that is subjected to continual
      adaptation to maintain tissue size and width, as well as structural integrity,
      including ligament fibers and bone modeling. PDL tissue is central in the
      periodontium to retain the tooth in the bone socket, and is currently recognized
      to include somatic mesenchymal stem cells that could reconstruct the
      periodontium. However, successful treatment using these stem cells to regenerate
      the periodontium efficiently has not yet been developed. In the present article,
      we discuss the contemporary standpoints and approaches for these stem cells in
      the field of regenerative medicine in dentistry.

PMID- 21861869
TI  - Detection of infectious disease outbreaks in twenty-two fragile states, 2000
      2010: a systematic review.
AB  - Fragile states are home to a sixth of the world's population, and their
      populations are particularly vulnerable to infectious disease outbreaks. Timely
      surveillance and control are essential to minimise the impact of these outbreaks,
      but little evidence is published about the effectiveness of existing surveillance
      systems. We did a systematic review of the circumstances (mode) of detection of
      outbreaks occurring in 22 fragile states in the decade 2000-2010 (i.e. all states
      consistently meeting fragility criteria during the timeframe of the review), as
      well as time lags from onset to detection of these outbreaks, and from detection
      to further events in their timeline. The aim of this review was to enhance the
      evidence base for implementing infectious disease surveillance in these complex,
      resource-constrained settings, and to assess the relative importance of different
      routes whereby outbreak detection occurs.We identified 61 reports concerning 38
      outbreaks. Twenty of these were detected by existing surveillance systems, but 10
      detections occurred following formal notifications by participating health
      facilities rather than data analysis. A further 15 outbreaks were detected by
      informal notifications, including rumours.There were long delays from onset to
      detection (median 29 days) and from detection to further events (investigation,
      confirmation, declaration, control). Existing surveillance systems yielded the
      shortest detection delays when linked to reduced barriers to health care and
      frequent analysis and reporting of incidence data.Epidemic surveillance and
      control appear to be insufficiently timely in fragile states, and need to be
      strengthened. Greater reliance on formal and informal notifications is warranted.
      Outbreak reports should be more standardised and enable monitoring of
      surveillance systems' effectiveness.

PMID- 21861870
TI  - The "smoker's paradox" in patients with acute coronary syndrome: a systematic
      review.
AB  - BACKGROUND: Smokers have been shown to have lower mortality after acute coronary
      syndrome than non-smokers. This has been attributed to the younger age, lower co
      morbidity, more aggressive treatment and lower risk profile of the smoker. Some
      studies, however, have used multivariate analyses to show a residual survival
      benefit for smokers; that is, the "smoker's paradox". The aim of this study was,
      therefore, to perform a systematic review of the literature and evidence
      surrounding the existence of the "smoker's paradox". METHODS: Relevant studies
      published by September 2010 were identified through literature searches using
      EMBASE (from 1980), MEDLINE (from 1963) and the Cochrane Central Register of
      Controlled Trials, with a combination of text words and subject headings used.
      English-language original articles were included if they presented data on
      hospitalised patients with defined acute coronary syndrome, reported at least in
      hospital mortality, had a clear definition of smoking status (including ex
      smokers), presented crude and adjusted mortality data with effect estimates, and
      had a study sample of > 100 smokers and > 100 non-smokers. Two investigators
      independently reviewed all titles and abstracts in order to identify potentially
      relevant articles, with any discrepancies resolved by repeated review and
      discussion. RESULTS: A total of 978 citations were identified, with 18 citations
      from 17 studies included thereafter. Six studies (one observational study, three
      registries and two randomised controlled trials on thrombolytic treatment)
      observed a "smoker's paradox". Between the 1980s and 1990s these studies enrolled
      patients with acute myocardial infarction (AMI) according to criteria similar to
      the World Health Organisation criteria from 1979. Among the remaining 11 studies
      not supporting the existence of the paradox, five studies represented patients
      undergoing contemporary management. CONCLUSION: The "smoker's paradox" was
      observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic
      era, whereas no studies of a contemporary population with acute coronary syndrome
      have found evidence for such a paradox.

PMID- 21861871
TI  - Dextromethorphan attenuated the higher vulnerability to inflammatory thermal
      hyperalgesia caused by prenatal morphine exposure in rat offspring.
AB  - BACKGROUND: Co-administration of dextromethorphan (DM) with morphine during
      pregnancy and throughout lactation has been found to reduce morphine physical
      dependence and tolerance in rat offspring. No evidence was presented, however,
      for the effect of DM co-administered with morphine during pregnancy on
      inflammatory hyperalgesia in morphine-exposed offspring. Therefore, we attempt to
      investigate the possible effect of prenatal morphine exposure on the
      vulnerability to hyperalgesia and the possible therapeutic effect of DM in the
      present study. METHODS: Fifty MUl of carrageenan (20 mg/ml) was injected
      subcutaneously into the plantar surface of the right hind paw in p18 rats to
      induce hyperalgesia. Mean paw withdrawal latency was measured in the plantar test
      to index the severity of hyperalgesia. Using Western blotting and RT-PCR, the
      quantitative analyses of NMDA receptor NR1 and NR2B subunits were performed in
      spinal cords from different groups of animals. RESULTS: In the carrageenan
      induced hyperalgesia model, rat offspring passively exposed to morphine developed
      a severe hyperalgesia on postnatal day 18 (p18), which also had a more rapid time
      course than those in the controls. Co-administration of DM with morphine in the
      dams prevented this adverse effect of morphine in the offspring rats. Western
      blot and RT-PCR analysis showed that the levels of protein and mRNA of NMDA
      receptor NR1 and NR2B subunits were significantly higher in the lumbar spinal
      cords of rats (p14) exposed to prenatal morphine; the co-administration of DM
      could reverse the effect of morphine on NR1 and attenuate the effect on NR2B.
      CONCLUSIONS: Thus, DM may have a great potential in the prevention of higher
      vulnerability to inflammatory thermal hyperalgesia in the offspring of morphine
      addicted mothers.

PMID- 21861872
TI  - A bacterial PriB with weak single-stranded DNA binding activity can stimulate the
      DNA unwinding activity of its cognate PriA helicase.
AB  - BACKGROUND: Bacterial DNA replication restart pathways facilitate reinitiation of
      DNA replication following disruptive encounters of a replisome with DNA damage,
      thereby allowing complete and faithful duplication of the genome. In Neisseria
      gonorrhoeae, the primosome proteins that catalyze DNA replication restart differ
      from the well-studied primosome proteins of E. coli with respect to the number of
      proteins involved and the affinities of their physical interactions: the
      PriA:PriB interaction is weak in E. coli, but strong in N. gonorrhoeae, and the
      PriB:DNA interaction is strong in E. coli, but weak in N. gonorrhoeae. In this
      study, we investigated the functional consequences of this affinity reversal.
      RESULTS: We report that N. gonorrhoeae PriA's DNA binding and unwinding
      activities are similar to those of E. coli PriA, and N. gonorrhoeae PriA's
      helicase activity is stimulated by its cognate PriB, as it is in E. coli. This
      finding is significant because N. gonorrhoeae PriB's single-stranded DNA binding
      activity is weak relative to that of E. coli PriB, and in E. coli, PriB's single
      stranded DNA binding activity is important for PriB stimulation of PriA helicase.
      Furthermore, a N. gonorrhoeae PriB variant defective for binding single-stranded
      DNA can stimulate PriA's helicase activity, suggesting that DNA binding by PriB
      might not be important for PriB stimulation of PriA helicase in N. gonorrhoeae.
      We also demonstrate that N. gonorrhoeae PriB stimulates ATP hydrolysis catalyzed
      by its cognate PriA. This activity of PriB has not been observed in E. coli, and
      could be important for PriB stimulation of PriA helicase in N. gonorrhoeae.
      CONCLUSIONS: The results of this study demonstrate that a bacterial PriB homolog
      with weak single-stranded DNA binding activity can stimulate the DNA unwinding
      activity of its cognate PriA helicase. While it remains unclear if N. gonorrhoeae
      PriB's weak DNA binding activity is required for PriB stimulation of PriA
      helicase, the ability of PriB to stimulate PriA-catalyzed ATP hydrolysis could
      play an important role. Thus, the weak interaction between N. gonorrhoeae PriB
      and DNA might be compensated for by the strong interaction between PriB and PriA,
      which could result in allosteric activation of PriA's ATPase activity.

PMID- 21861873
TI  - Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen.
AB  - BACKGROUND: During pregnancy the immune system of the mother must protect any
      activation that may negatively affect the fetus. Changes in susceptibility to
      infection as well as resolution of some autoimmune disorders represent empirical
      evidence for pregnancy related alterations in immunity. Sex hormones reach
      extremely high levels during pregnancy and have been shown to have direct effects
      on many immune functions including the antiviral response of dendritic cells.
      Among the immunologically active proteins secreted by monocyte derived DCs (MDDC)
      are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a
      broad spectrum of microbicidal activity and has also been shown to link innate to
      adaptive immunity by attracting T cells and immature DCs, which are essential for
      initiating and polarizing the immune response. METHODS: We compare culture
      generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic
      cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha
      defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2
      or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs
      from blood and also measure the levels of these anti-microbial peptides along
      pregnancy. RESULTS: We show that mDCs and pDCs constitutively produce alpha
      defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3
      production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not
      affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1
      3 production by mDCs was reduced in the later stages of pregnancy in 40% of the
      patients. CONCLUSIONS: Here, we demonstrate that mDCs and pDCs secrete alpha
      defensins 1-3 and present a novel effect of E2 on the secretion of alpha
      defensins 1-3 by dendritic cells.

PMID- 21861874
TI  - A glycine zipper motif mediates the formation of toxic beta-amyloid oligomers in
      vitro and in vivo.
AB  - BACKGROUND: The beta-amyloid peptide (Abeta) contains a Gly-XXX-Gly-XXX-Gly motif
      in its C-terminal region that has been proposed to form a "glycine zipper" that
      drives the formation of toxic Abeta oligomers. We have tested this hypothesis by
      examining the toxicity of Abeta variants containing substitutions in this motif
      using a neuronal cell line, primary neurons, and a transgenic C. elegans model.
      RESULTS: We found that a Gly37Leu substitution dramatically reduced Abeta
      toxicity in all models tested, as measured by cell dysfunction, cell death,
      synaptic alteration, or tau phosphorylation. We also demonstrated in multiple
      models that Abeta Gly37Leu is actually anti-toxic, thereby supporting the
      hypothesis that interference with glycine zipper formation blocks assembly of
      toxic Abeta oligomers. To test this model rigorously, we engineered second site
      substitutions in Abeta predicted by the glycine zipper model to compensate for
      the Gly37Leu substitution and expressed these in C. elegans. We show that these
      second site substitutions restore in vivo Abetatoxicity, further supporting the
      glycine zipper model. CONCLUSIONS: Our structure/function studies support the
      view that the glycine zipper motif present in the C-terminal portion of Abeta
      plays an important role in the formation of toxic Abeta oligomers. Compounds
      designed to interfere specifically with formation of the glycine zipper could
      have therapeutic potential.

PMID- 21861875
TI  - Biocompatible micro-sized cell culture chamber for the detection of nanoparticle
      induced IL8 promoter activity on a small cell population.
AB  - In most conventional in vitro toxicological assays, the response of a complete
      cell population is averaged, and therefore, single-cell responses are not
      detectable. Such averaging might result in misinterpretations when only
      individual cells within a population respond to a certain stimulus. Therefore,
      there is a need for non-invasive in vitro systems to verify the toxicity of
      nanoscale materials. In the present study, a micro-sized cell culture chamber
      with a silicon nitride membrane (0.16 mm2) was produced for cell cultivation and
      the detection of specific cell responses. The biocompatibility of the microcavity
      chip (MCC) was verified by studying adipogenic and neuronal differentiation.
      Thereafter, the suitability of the MCC to study the effects of nanoparticles on a
      small cell population was determined by using a green fluorescence protein-based
      reporter cell line. Interleukin-8 promoter (pIL8) induction, a marker of an
      inflammatory response, was used to monitor immune activation. The validation of
      the MCC-based method was performed using well-characterized gold and silver
      nanoparticles. The sensitivity of the new method was verified comparing the
      quantified pIL8 activation via MCC-based and standard techniques. The results
      proved the biocompatibility and the sensitivity of the microculture chamber, as
      well as a high optical quality due to the properties of Si3N4. The MCC-based
      method is suited for threshold- and time-dependent analysis of nanoparticle
      induced IL8 promoter activity. This novel system can give dynamic information at
      the level of adherent single cells of a small cell population and presents a new
      non-invasive in vitro test method to assess the toxicity of nanomaterials and
      other compounds.PACS: 85.35.Be, 81.16.Nd, 87.18.Mp.

PMID- 21861876
TI  - Saudi mothers' preferences about breaking bad news concerning newborns: a
      structured verbal questionnaire.
AB  - BACKGROUND: Breaking bad news (BBN) to parents whose newborn has a major disease
      is an ethical dilemma. In Saudi Arabia, BBN about newborns is performed according
      to the parental preferences that have been reported from non-Arabic/non-Islamic
      countries. Saudi mothers' preferences about BBN have not yet been studied.
      Therefore, we aimed to elicit the preferences of Saudi mothers about BBN
      concerning newborns. METHODS: We selected a convenience sample of 402 Saudi
      mothers, aged 18-50 years, who had no previous experience with BBN. We selected
      them via a simple number-randomization scheme from the premises of a level III
      Saudi hospital between October of 2009 and January of 2011. We used a
      hypothetical situation (BBN about trisomy 21) to elicit their preferences about
      BBN concerning newborns via a structured verbal questionnaire composed of 12
      multiple-choice questions. We expressed their preferences as percentages (95%
      confidence interval), and we used the Kendall's W test (W) to assess the degree
      of agreement in preferences. RESULTS: The Saudi mothers preferred that BBN be
      conducted with both parents together (64% [60-69]), albeit with weak levels of
      agreement (W = 0.29). They showed moderate agreement in their preferences that
      BBN should be conducted early (79% [75-83], W = 0.48), in detail (81% [77-85], W
      = 0.52), in person (88% [85-91], W = 0.58), and in a quiet setting (86% [83-90],
      W = 0.53). With extremely weak agreement, they preferred to have a known person
      present for support during BBN (56% [51-61], W = 0.01), to have close bodily
      contact with their babies (66% [61-70], W = 0.10), and to have no another
      patients present (64% [59-68], W = 0.08). They showed moderate levels of
      agreement in their desires to detail, in advance, their preferences about process
      of BBN by giving a reversible, written informed consent that could be utilized
      for guidance, if needed (80% [76-84], W = 0.36). CONCLUSIONS: In our experience,
      Saudi mothers' preferences about BBN concerning newborns are varied, suggesting
      that a "one-size-fits-all" approach is inappropriate. A reversible, written
      informed consent detailing their preferences about BBN that would be kept in
      their medical records and utilized for guidance, if needed, may be the best
      solution, given this level of diversity. These findings merit further study.

PMID- 21861877
TI  - Enzyme production by filamentous fungi: analysis of the secretome of Trichoderma
      reesei grown on unconventional carbon source.
AB  - BACKGROUND: Spent hydrolysates from bioethanolic fermentation processes based on
      agricultural residues have potential as an abundant and inexpensive source of
      pentose sugars and acids that could serve as nutrients for industrial enzyme
      producing microorganisms, especially filamentous fungi. However, the enzyme
      mixtures produced in such media are poorly defined. In this study, the secretome
      of Trichoderma reesei Rut C-30 grown either on a spent hydrolysate model medium
      (SHMM) or on a lactose-based standard medium (LBSM) was explored using
      proteomics. RESULTS: Our results show that both the SHMM and LBSM serve as
      excellent growth media for T. reesei Rut C-30. In total, 52 protein spots on 2-D
      gels were identified by using matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) and electrospray ionization liquid chromatography tandem
      mass spectrometry (ESI-LC MS/MS). As expected, a considerable number of the
      identified proteins were related to the degradation of lignocellulosic biomass.
      The enzyme production profiles in the two media were similar, but beta
      glucosidase and beta-galactosidase were only produced in LBSM. The main
      cellobiohydrolases (Cel7A/Cel6A) and endoglucanases (Cel7B/Cel5A) were identified
      in both media and the cellobiohydrolases, i.e. Cel7A and Cel6A, were the most
      abundant cellulolytic enzymes. Moreover, both media can also serve as a potent
      inducer of xylanolytic enzymes. Several key enzymes involved in sugar
      assimilation and regulation of cellulase formation were identified, and were
      found to be differentially expressed in the two growth media. CONCLUSIONS: This
      study not only provides a catalogue of the prevalent proteins secreted by T.
      reesei in the two media, but the results also suggest that production of
      hydrolytic enzymes using unconventional carbon sources, such as components in
      spent hydrolysates, deserves further attention in the future.

PMID- 21861878
TI  - The impact of open versus closed format ICU admission practices on the outcome of
      high risk surgical patients: a cohort analysis.
AB  - BACKGROUND: In the year 2000, the organizational structure of the ICU in the
      Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The
      objective of this study was to evaluate the effect of this organizational change
      on outcome in high risk surgical patients. METHODS: The medical records of all
      consecutive high risk surgical patients admitted to the ICU from 1996 to 1998
      (open format) and from 2003 to 2005 (closed format), were reviewed. High-risk
      patients were defined according to the Identification of Risk in Surgical
      patients (IRIS) score. Parameters studied were: mortality, morbidity, ICU length
      of stay (LOS) and hospital LOS. RESULTS: Mortality of ICU patients was 25.7% in
      the open format group and 15.8% in the closed format group (p = 0.01). Morbidity
      decreased from 48.6% to 46.1% (p = 0.6). The average length of hospital stay was
      17 days in the open format group, and 21 days in the closed format group (p =
      0.03). CONCLUSIONS: High risk surgical patients in the ICU are patients that have
      undergone complex and often extensive surgery. These patients are in need of
      specialized treatment and careful monitoring for maximum safety and optimal care.
      Our results suggest that closed format is a more favourable setting than open
      format to minimize the effects of high risk surgery, and to warrant safe outcome
      in this patient group.

PMID- 21861879
TI  - Bilateral testicular self-castration due to cannabis abuse: a case report.
AB  - INTRODUCTION: The self-mutilating patient is an unusual psychiatric presentation
      in the emergency room. Nonetheless, serious underlying psychiatric pathology and
      drug abuse are important background risk factors. A careful stepwise approach in
      the emergency room is essential, although the prognosis, follow-up, and eventual
      rehabilitation can be problematic.We present a unique and original case of
      bilateral self-castration caused by cannabis abuse. CASE PRESENTATION: We report
      a case of a 40-year-old Berber man, who was presented to our emergency room with
      externalization of both testes using his long fingernails, associated with
      hemodynamic shock. After stabilization of his state, our patient was admitted to
      the operating room where hemostasis was achieved. CONCLUSION: The clinical
      characteristics of self-mutilation are manifold and there is a lack of agreement
      about its etiology. The complex behavior associated with drug abuse may be one
      cause of self-mutilation. Dysfunction of the inhibitory brain circuitry caused by
      substance abuse could explain why this cannabis-addicted patient lost control and
      self-mutilated. To the best of our knowledge, this is the first case report which
      presents an association between self-castration and cannabis abuse.

PMID- 21861880
TI  - The application of foraging theory to the information searching behaviour of
      general practitioners.
AB  - BACKGROUND: General Practitioners (GPs) employ strategies to identify and
      retrieve medical evidence for clinical decision making which take workload and
      time constraints into account. Optimal Foraging Theory (OFT) initially developed
      to study animal foraging for food is used to explore the information searching
      behaviour of General Practitioners. This study is the first to apply foraging
      theory within this context.Study objectives were: 1. To identify the sequence and
      steps deployed in identifiying and retrieving evidence for clinical decision
      making. 2. To utilise Optimal Foraging Theory to assess the effectiveness and
      efficiency of General Practitioner information searching. METHODS: GPs from the
      Wellington region of New Zealand were asked to document in a pre-formatted
      logbook the steps and outcomes of an information search linked to their clinical
      decision making, and fill in a questionnaire about their personal, practice and
      information-searching backgrounds. RESULTS: A total of 115/155 eligible GPs
      returned a background questionnaire, and 71 completed their information search
      logbook. GPs spent an average of 17.7 minutes addressing their search for
      clinical information. Their preferred information sources were discussions with
      colleagues (38% of sources) and books (22%). These were the two most profitable
      information foraging sources (15.9 min and 9.5 min search time per answer,
      compared to 34.3 minutes in databases). GPs nearly always accessed another source
      when unsuccessful (95% after 1st source), and frequently when successful (43%
      after 2nd source). Use of multiple sources accounted for 41% of searches, and
      increased search success from 70% to 89%. CONCLUSIONS: By consulting in foraging
      terms the most 'profitable' sources of information (colleagues, books), rapidly
      switching sources when unsuccessful, and frequently double checking, GPs achieve
      an efficient trade-off between maximizing search success and information
      reliability, and minimizing searching time. As predicted by foraging theory, GPs
      trade time-consuming evidence-based (electronic) information sources for sources
      with a higher information reward per unit time searched. Evidence-based practice
      must accommodate these 'real world' foraging pressures, and Internet resources
      should evolve to deliver information as effectively as traditional methods of
      information gathering.

PMID- 21861881
TI  - Improving the prediction of protein binding sites by combining heterogeneous data
      and Voronoi diagrams.
AB  - BACKGROUND: Protein binding site prediction by computational means can yield
      valuable information that complements and guides experimental approaches to
      determine the structure of protein complexes. Predictions become even more
      relevant and timely given the current resolution of protein interaction maps,
      where there is a very large and still expanding gap between the available
      information on: (i) which proteins interact and (ii) how proteins interact.
      Proteins interact through exposed residues that present differential
      physicochemical properties, and these can be exploited to identify protein
      interfaces. RESULTS: Here we present VORFFIP, a novel method for protein binding
      site prediction. The method makes use of broad set of heterogeneous data and
      defined of residue environment, by means of Voronoi Diagrams that are integrated
      by a two-steps Random Forest ensemble classifier. Four sets of residue features
      (structural, energy terms, sequence conservation, and crystallographic B-factors)
      used in different combinations together with three definitions of residue
      environment (Voronoi Diagrams, sequence sliding window, and Euclidian distance)
      have been analyzed in order to maximize the performance of the method.
      CONCLUSIONS: The integration of different forms information such as structural
      features, energy term, evolutionary conservation and crystallographic B-factors,
      improves the performance of binding site prediction. Including the information of
      neighbouring residues also improves the prediction of protein interfaces. Among
      the different approaches that can be used to define the environment of exposed
      residues, Voronoi Diagrams provide the most accurate description. Finally,
      VORFFIP compares favourably to other methods reported in the recent literature.

PMID- 21861882
TI  - Differential toll-like receptor 3 (TLR3) expression and apoptotic response to
      TLR3 agonist in human neuroblastoma cells.
AB  - BACKGROUND: Toll-like receptor-3 (TLR-3) is a critical component of innate immune
      system against dsRNA viruses and is expressed in the central nervous system.
      However, it remains unknown whether TLR3 may serve as a therapeutic target in
      human neuroblastoma (NB). METHODS: TLR3 expression in human NB samples was
      examined by immunohistochemical analysis. Quantitative RT-PCR and western blot
      was used to determine TLR3 expression in three human NB cell lines. The effect of
      TLR3 agonist, polyinosinic-polycytidylic acid (poly(I:C)), on the growth of human
      NB cells was evaluated by WST-1 cell proliferation assay, flow cytometry
      analysis, and immunoblot analysis. Blockade of TLR3 signaling was achieved using
      TLR3 neutralizing antibody, small interference RNA, and 2-aminopurine (2-AP), an
      inhibitor of protein kinase R (PKR), an interferon-induced, double-stranded RNA
      activated protein kinase. RESULTS: In immunohistochemical studies, TLR3 mainly
      expressed in the cytoplasm of ganglion cells and in some neuroblastic cells, but
      not in the stromal cells in human NB tissues. Among three human NB cell lines
      analyzed, TLR3 was significantly up-regulated in SK-N-AS cells at mRNA and
      protein level compared with other two low TLR3- expressing NB cells. Treatment
      with poly(I:C) elicited significant growth inhibition and apoptosis only in high
      TLR3-expressing SK-N-AS cells, but not in low TLR3-expressing SK-N-FI and SK-N-DZ
      cells. Moreover, poly(I:C) treatment significantly stimulated the activities of
      PKR, interferon regulatory factor 3 (IRF-3) and caspase-3 in SK-N-AS cells.
      Application of TLR3 neutralizing antibody or small interference RNA (siRNA)
      reduced the poly(I:C)-induced inhibition of cell proliferation and apoptosis in
      SK-N-AS cells. On the contrary, ectopic TLR3 expression enhanced the sensitivity
      of low TLR3-expressing NB cells to poly(I:C). Finally, application of 2-AP
      attenuated the poly(I:C)-induced IRF-3 and caspase-3 activation in SK-N-AS cells.
      CONCLUSION: The present study demonstrates that TLR3 is expressed in a subset of
      NB cells. Besides, TLR3/PKR/IRF-3/capase-3 pathway is implicated in the selective
      cytotoxicity of TLR3 agonist towards high TLR3-expressing NB cells.

PMID- 21861883
TI  - "Glucose and ethanol-dependent transcriptional regulation of the astaxanthin
      biosynthesis pathway in Xanthophyllomyces dendrorhous".
AB  - BACKGROUND: The yeast Xanthophyllomyces dendrorhous is one of the most promising
      and economically attractive natural sources of astaxanthin. The biosynthesis of
      this valuable carotenoid is a complex process for which the regulatory mechanisms
      remain mostly unknown. Several studies have shown a strong correlation between
      the carbon source present in the medium and the amount of pigments synthesized.
      Carotenoid production is especially low when high glucose concentrations are used
      in the medium, while a significant increase is observed with non-fermentable
      carbon sources. However, the molecular basis of this phenomenon has not been
      established. RESULTS: In this work, we showed that glucose caused transcriptional
      repression of the three genes involved in the synthesis of astaxanthin from
      geranylgeranyl pyrophosphate in X. dendrorhous, which correlates with a complete
      inhibition of pigment synthesis. Strikingly, this regulatory response was
      completely altered in mutant strains that are incapable of synthesizing
      astaxanthin. However, we found that addition of ethanol caused the induction of
      crtYB and crtS gene expression and promoted de novo synthesis of carotenoids. The
      induction of carotenogenesis was noticeable as early as 24 h after ethanol
      addition. CONCLUSION: For the first time, we demonstrated that carbon source
      dependent regulation of astaxanthin biosynthesis in X. dendrorhous involves
      changes at the transcriptional level. Such regulatory mechanism provides an
      explanation for the strong and early inhibitory effect of glucose on the
      biosynthesis of this carotenoid.

PMID- 21861884
TI  - Biological interaction networks are conserved at the module level.
AB  - BACKGROUND: Orthologous genes are highly conserved between closely related
      species and biological systems often utilize the same genes across different
      organisms. However, while sequence similarity often implies functional
      similarity, interaction data is not well conserved even for proteins with high
      sequence similarity. Several recent studies comparing high throughput data
      including expression, protein-protein, protein-DNA, and genetic interactions
      between close species show conservation at a much lower rate than expected.
      RESULTS: In this work we collected comprehensive high-throughput interaction
      datasets for four model organisms (S. cerevisiae, S. pombe, C. elegans, and D.
      melanogaster) and carried out systematic analyses in order to explain the
      apparent lower conservation of interaction data when compared to the conservation
      of sequence data. We first showed that several previously proposed hypotheses
      only provide a limited explanation for such lower conservation rates. We combined
      all interaction evidences into an integrated network for each species and
      identified functional modules from these integrated networks. We then demonstrate
      that interactions that are part of functional modules are conserved at much
      higher rates than previous reports in the literature, while interactions that
      connect between distinct functional modules are conserved at lower rates.
      CONCLUSIONS: We show that conservation is maintained between species, but mainly
      at the module level. Our results indicate that interactions within modules are
      much more likely to be conserved than interactions between proteins in different
      modules. This provides a network based explanation to the observed conservation
      rates that can also help explain why so many biological processes are well
      conserved despite the lower levels of conservation for the interactions of
      proteins participating in these processes.Accompanying website:
      http://www.sb.cs.cmu.edu/CrossSP.

PMID- 21861885
TI  - Environmental, entomological, socioeconomic and behavioural risk factors for
      malaria attacks in Amerindian children of Camopi, French Guiana.
AB  - BACKGROUND: Malaria is a major health issue in French Guiana. Amerindian
      communities remain the most affected. A previous study in Camopi highlighted the
      predominant role of environmental factors in the occurrence of malaria. However,
      all parameters involved in the transmission were not clearly identified. A new
      survey was conducted in order to clarify the risk factors for the presence of
      malaria cases in Camopi. METHODS: An open cohort of children under seven years of
      age was set up on the basis of biologically confirmed malaria cases for the
      period 2001-2009. Epidemiological and observational environmental data were
      collected using two structured questionnaires. Data were analysed with a multiple
      failures multivariate Cox model. The influence of climate and the river level on
      malaria incidence was evaluated by time-series analysis. Relationships between
      Anopheles darlingi human biting rates and malaria incidence rates were estimated
      using Spearman's rank correlation. RESULTS: The global annual incidence over the
      nine-year period was 238 per 1,000 for Plasmodium falciparum, 514 per 1,000 for
      Plasmodium visa and 21 per 1,000 for mixed infections. The multivariate survival
      analysis associated higher malaria incidence with living on the Camopi riverside
      vs. the Oyapock riverside, far from the centre of the Camopi hamlet, in a home
      with numerous occupants and going to sleep late. On the contrary, living in a
      house cleared of all vegetation within 50 m and at high distance of the forest
      were associated with a lower risk. Meteorological and hydrological
      characteristics appeared to be correlated with malaria incidence with different
      lags. Anopheles darlingi human biting rate was also positively correlated to
      incident malaria in children one month later. CONCLUSIONS: Malaria incidence in
      children remains high in young children despite the appearance of immunity in
      children around three years of age. The closeness environment but also the
      meteorological parameters play an important role in malaria transmission among
      children under seven years of age in Camopi.

PMID- 21861886
TI  - The NIHR Collaborations for Leadership in Applied Health Research and Care
      (CLAHRC) for Greater Manchester: combining empirical, theoretical and
      experiential evidence to design and evaluate a large-scale implementation
      strategy.
AB  - BACKGROUND: In response to policy recommendations, nine National Institute for
      Health Research (NIHR) Collaborations for Leadership in Applied Health Research
      and Care (CLAHRCs) were established in England in 2008, aiming to create closer
      working between the health service and higher education and narrow the gap
      between research and its implementation in practice. The Greater Manchester (GM)
      CLAHRC is a partnership between the University of Manchester and twenty National
      Health Service (NHS) trusts, with a five-year mission to improve healthcare and
      reduce health inequalities for people with cardiovascular conditions. This paper
      outlines the GM CLAHRC approach to designing and evaluating a large-scale,
      evidence- and theory-informed, context-sensitive implementation programme.
      DISCUSSION: The paper makes a case for embedding evaluation within the design of
      the implementation strategy. Empirical, theoretical, and experiential evidence
      relating to implementation science and methods has been synthesised to formulate
      eight core principles of the GM CLAHRC implementation strategy, recognising the
      multi-faceted nature of evidence, the complexity of the implementation process,
      and the corresponding need to apply approaches that are situationally relevant,
      responsive, flexible, and collaborative. In turn, these core principles inform
      the selection of four interrelated building blocks upon which the GM CLAHRC
      approach to implementation is founded. These determine the organizational
      processes, structures, and roles utilised by specific GM CLAHRC implementation
      projects, as well as the approach to researching implementation, and comprise:
      the Promoting Action on Research Implementation in Health Services (PARIHS)
      framework; a modified version of the Model for Improvement; multiprofessional
      teams with designated roles to lead, facilitate, and support the implementation
      process; and embedded evaluation and learning. SUMMARY: Designing and evaluating
      a large-scale implementation strategy that can cope with and respond to the local
      complexities of implementing research evidence into practice is itself complex
      and challenging. We present an argument for adopting an integrative, co
      production approach to planning and evaluating the implementation of research
      into practice, drawing on an eclectic range of evidence sources.

PMID- 21861887
TI  - Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of
      bronchial epithelium in COPD.
AB  - BACKGROUND: Cigarette smoke, the major risk factor for COPD, is known to activate
      matrix metalloproteinases in airway epithelium. We investigated whether
      metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM)17,
      contribute to increased pro-inflammatory epithelial responses with respect to the
      release of IL-8 and TGF-alpha, cytokines implicated in COPD pathogenesis.
      METHODS: We studied the effects of cigarette smoke extract (CSE) and
      metalloproteinase inhibitors on TGF-alpha and IL-8 release in primary bronchial
      epithelial cells (PBECs) from COPD patients, healthy smokers and non-smokers.
      RESULTS: We observed that TGF-alpha was mainly shed by ADAM17 in PBECs from all
      groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF
      alpha shedding, but was significantly inhibited by broad-spectrum
      metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-alpha
      shedding, while it slightly augmented the production of IL-8. This was
      accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP)-3 levels,
      suggesting that CSE does not directly but rather indirectly alter activity of
      ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas
      baseline TGF-alpha shedding was lower in COPD PBECs, the early release of IL-8
      (likely due to its shedding) was higher in PBECs from COPD than healthy smokers.
      Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while
      baseline TIMP-3 levels were similar between groups. CONCLUSIONS: Our data
      indicate that IL-8 secretion is regulated independently from ADAM17 activity and
      TGF-alpha shedding and that particularly its early release is differentially
      regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive
      metalloproteinases could potentially contribute to IL-8 release, these may be
      interesting targets to further investigate novel therapeutic strategies in COPD.

PMID- 21861888
TI  - A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus
      capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line
      treatment of metastatic colorectal cancer: the AIO KRK 0110 trial/ML22011 trial.
AB  - BACKGROUND: Several randomized trials have indicated that combination
      chemotherapy applied in metastatic colorectal cancer (mCRC) does not
      significantly improve overall survival when compared to the sequential use of
      cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates
      the question whether this statement holds true also for bevacizumab-based first
      line treatment including escalation- and de-escalation strategies.
      METHODS/DESIGN: The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open
      label randomized phase III trial comparing the efficacy and safety of
      capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus
      bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal
      cancer. Patients with unresectable metastatic colorectal cancer, Eastern
      Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a
      1:1 ratio to receive either capecitabine 1250 mg/m(2) bid for 14d (d1-14) plus
      bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m(2) BID for 14d
      (d1-14), irinotecan 200 mg/m(2) (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B).
      Patients included into this trial are required to consent to the analysis of
      tumour tissue and blood for translational investigations. In Arm A, treatment
      escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive
      disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible
      after 6 months of treatment or in case of irinotecan-associated toxicity. Re
      escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to
      failure of strategy (TFS). Secondary endpoints are overall response rate (ORR),
      overall survival, progression-free survival, safety and quality of life.
      CONCLUSION: The AIO KRK 0110 trial is designed for patients with disseminated,
      but asymptomatic mCRC who are not potential candidates for surgical resection of
      metastasis. Two bevacizumab-based strategies are compared: one starting as single
      agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another
      starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to
      Cape-Bev and subsequent re-escalation if necessary. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier NCT01249638 EudraCT-No.: 2009-013099-38.

PMID- 21861889
TI  - A modified score to identify and discriminate neuropathic pain: a study on the
      German version of the Neuropathic Pain Symptom Inventory (NPSI).
AB  - BACKGROUND: Neuropathic pain must be correctly diagnosed for optimal treatment.
      The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed
      in its original French version to evaluate the different symptoms of neuropathic
      pain. We hypothesized that the NPSI might also be used to differentiate
      neuropathic from non-neuropathic pain. METHODS: We translated the NPSI into
      German using a standard forward-backward translation and administered it in a
      case-control design to patients with neuropathic (n = 68) and non-neuropathic
      pain (headache and osteoarthritis, n = 169) to validate it and to analyze its
      discriminant properties, its sensitivity to change, and to detect neuropathic
      pain subgroups with distinct profiles. RESULTS: Using a sum score (the NPSI-G
      score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of
      the graded chronic pain scale) and could distinguish between neuropathic and
      other pain on a group basis, but not for individual patients. Post hoc
      development of a discriminant score with optimized diagnostic properties to
      distinguish neuropathic pain from non-neuropathic pain resulted in an instrument
      with high sensitivity (91%) and acceptable specificity (70%). We detected six
      different pain profiles in the patient group with neuropathic pain; three
      profiles were found to be distinct. CONCLUSIONS: The NPSI-G potentially combines
      the properties of a diagnostic tool and an instrument to identify subtypes of
      neuropathic pain.

PMID- 21861890
TI  - A registry-based follow-up study, comparing the incidence of cardiovascular
      disease in native Danes and immigrants born in Turkey, Pakistan and the former
      Yugoslavia: do social inequalities play a role?
AB  - BACKGROUND: This study compared the incidence of cardiovascular disease (CVD) and
      acute myocardial infarction (AMI) between native Danes and immigrants born in
      Turkey, Pakistan and the former Yugoslavia. Furthermore, we examined whether
      different indicators of socioeconomic status (SES), such as employment, income
      and housing conditions influenced potential differences. METHODS: In this
      registry-based follow-up study individuals were identified in a large database
      that included individuals from two major regions in Denmark, corresponding to
      about 60% of the Danish population. Incident cases of CVD and AMI included fatal
      and non-fatal events and were taken from registries. Using Cox regression models,
      we estimated incidence rates at 5-year follow-up. RESULTS: Immigrant men and
      women from Turkey and Pakistan had an increased incidence of CVD, compared with
      native Danish men. In the case of AMI, a similar pattern was observed; however,
      differences were more pronounced. Pakistanis and Turks with a shorter duration of
      residence had a lower incidence, compared with those of a longer residence.
      Generally, no notable differences were observed between former Yugoslavians and
      native Danes. In men, differences in CVD and AMI were reduced after adjustment
      for SES, in particular, among Turks regarding CVD. In women, effects were
      particularly reduced among Yugoslavians in the case of CVD and in Turks in the
      case of CVD and AMI after adjustment for SES. CONCLUSIONS: In conclusion, country
      of birth-related differences in the incidence of CVD and AMI were observed. At
      least some of the differences that we uncovered were results of a socioeconomic
      effect. Duration of residence also played a certain role. Future studies should
      collect and test different indicators of SES in studies of CVD among immigrants.

PMID- 21861891
TI  - High resolution CT and histological findings in idiopathic pleuroparenchymal
      fibroelastosis: features and differential diagnosis.
AB  - Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described
      clinical-pathologic entity characterized by pleural and subpleural parenchymal
      fibrosis, mainly in the upper lobes. As this disease is extremely rare (only 7
      cases have been described in the literature to date) poorly defined cases of
      IPPFE can go unrecognized.The clinical course of disease is progressive and
      prognosis is poor, with no therapeutic options other than lung transplantation
      currently available, yet. The aim of this report is to describe two further cases
      of this rare disease, reviewing CT, clinical and histological features.

PMID- 21861892
TI  - Adolescent girls' and parents' views on recruiting and retaining girls into an
      after-school dance intervention: implications for extra-curricular physical
      activity provision.
AB  - BACKGROUND: Many adolescents are not sufficiently active and girls are less
      active than boys. Physical activity interventions delivered during curriculum
      time have reported weak effects. More sustained changes in physical activity may
      be obtained by facilitating participation in enjoyable activities. Dance is the
      favourite activity of UK girls but there is a shortage of dance provision. Dance
      sessions delivered after the school day could prove to be an effective means of
      engaging adolescent girls in physical activity. There is a lack of information
      about the factors that would affect girls' recruitment and retention in an after
      school dance programme. METHODS: Focus groups were conducted with 65, Year 7 (11
      12 year old) girls from 4 secondary schools in Bristol. In-depth phone interviews
      were also conducted with 16 (4 per school) of the girls' parents. Interviews and
      focus groups examined issues that would affect recruitment into the intervention,
      strategies that could be used to attract girls who have little or no previous
      experience in dance, any factors that would increase their interest in
      participating in an after-school dance programme and any factors that would
      affect retention in the programme. All interviews and focus groups were digitally
      recorded and thematically analysed. RESULTS: Girls reported that a taster session
      in which they had an opportunity to sample the intervention content and "word of
      mouth" campaigns by peers, who did not need to be their friends, would encourage
      them to participate in an after-school dance programme. Sessions that maximised
      enjoyment and facilitated socialisation opportunities would enhance retention.
      Parents reported that encouraging groups of friends to join the programme, and
      stressing the enjoyment of the session would increase participation. CONCLUSIONS:
      Recruitment and retention campaigns that focus on enjoyment, socialisation,
      mastery, goal setting and relating to other girls may be effective strategies for
      recruiting and retaining girls in an after-school dance programme. These factors
      are consistent with well-established theories of individual behaviour change such
      as self-determination theory and social cognitive theory. Recruitment and
      retention campaigns that are targeted to address theoretically derived mediators
      of behaviour may be more effective than traditional approaches.

PMID- 21861893
TI  - Gallus gallus NEU3 sialidase as model to study protein evolution mechanism based
      on rapid evolving loops.
AB  - BACKGROUND: Large surface loops contained within compact protein structures and
      not involved in catalytic process have been proposed as preferred regions for
      protein family evolution. These loops are subjected to lower sequence constraints
      and can evolve rapidly in novel structural variants. A good model to study this
      hypothesis is represented by sialidase enzymes. Indeed, the structure of
      sialidases is a beta-propeller composed by anti-parallel beta-sheets connected by
      loops that suit well with the rapid evolving loop hypothesis. These features
      prompted us to extend our studies on this protein family in birds, to get
      insights on the evolution of this class of glycohydrolases. RESULTS: Gallus
      gallus (Gg) genome contains one NEU3 gene encoding a protein with a unique 188
      amino acid sequence mainly constituted by a peptide motif repeated six times in
      tandem with no homology with any other known protein sequence. The repeat region
      is located at the same position as the roughly 80 amino acid loop characteristic
      of mammalian NEU4. Based on molecular modeling, all these sequences represent a
      connecting loop between the first two highly conserved beta-strands of the fifth
      blade of the sialidase beta-propeller. Moreover this loop is highly variable in
      sequence and size in NEU3 sialidases from other vertebrates. Finally, we found
      that the general enzymatic properties and subcellular localization of Gg NEU3 are
      not influenced by the deletion of the repeat sequence. CONCLUSION: In this study
      we demonstrated that sialidase protein structure contains a surface loop, highly
      variable both in sequence and size, connecting two conserved beta-sheets and
      emerging on the opposite site of the catalytic crevice. These data confirm that
      sialidase family can serve as suitable model for the study of the evolutionary
      process based on rapid evolving loops, which may had occurred in sialidases.
      Giving the peculiar organization of the loop region identified in Gg NEU3, this
      protein can be considered of particular interest in such evolutionary studies and
      to get deeper insights in sialidase evolution.

PMID- 21861895
TI  - Globalization and its methodological discontents: Contextualizing globalization
      through the study of HIV/AIDS.
AB  - There remains considerable discontent between globalization scholars about how
      to conceptualize its meaning and in regards to epistemological and methodological
      questions concerning how we can come to understand how these processes ultimately
      operate, intersect and transform our lives. This article argues that to better
      understand what globalization is and how it affects issues such as global health,
      we must take a differentiating approach, which focuses on how the multiple
      processes of globalization are encountered and informed by different social
      groups and with how these encounters are experienced within particular contexts.
      The article examines the heuristic properties of qualitative field research as a
      means to help better understand how the intersections of globalization are
      manifested within particular locations. To do so, the article focuses on three
      recent case studies conducted on globalization and HIV/AIDS and explores how
      these cases can help us to understand the contextual permutations involved within
      the processes of globalization.

PMID- 21861894
TI  - De-identifying a public use microdata file from the Canadian national discharge
      abstract database.
AB  - BACKGROUND: The Canadian Institute for Health Information (CIHI) collects
      hospital discharge abstract data (DAD) from Canadian provinces and territories.
      There are many demands for the disclosure of this data for research and analysis
      to inform policy making. To expedite the disclosure of data for some of these
      purposes, the construction of a DAD public use microdata file (PUMF) was
      considered. Such purposes include: confirming some published results, providing
      broader feedback to CIHI to improve data quality, training students and fellows,
      providing an easily accessible data set for researchers to prepare for analyses
      on the full DAD data set, and serve as a large health data set for computer
      scientists and statisticians to evaluate analysis and data mining techniques. The
      objective of this study was to measure the probability of re-identification for
      records in a PUMF, and to de-identify a national DAD PUMF consisting of 10% of
      records. METHODS: Plausible attacks on a PUMF were evaluated. Based on these
      attacks, the 2008-2009 national DAD was de-identified. A new algorithm was
      developed to minimize the amount of suppression while maximizing the precision of
      the data. The acceptable threshold for the probability of correct re
      identification of a record was set at between 0.04 and 0.05. Information loss was
      measured in terms of the extent of suppression and entropy. RESULTS: Two
      different PUMF files were produced, one with geographic information, and one with
      no geographic information but more clinical information. At a threshold of 0.05,
      the maximum proportion of records with the diagnosis code suppressed was 20%, but
      these suppressions represented only 8-9% of all values in the DAD. Our
      suppression algorithm has less information loss than a more traditional approach
      to suppression. Smaller regions, patients with longer stays, and age groups that
      are infrequently admitted to hospitals tend to be the ones with the highest rates
      of suppression. CONCLUSIONS: The strategies we used to maximize data utility and
      minimize information loss can result in a PUMF that would be useful for the
      specific purposes noted earlier. However, to create a more detailed file with
      less information loss suitable for more complex health services research, the
      risk would need to be mitigated by requiring the data recipient to commit to a
      data sharing agreement.

PMID- 21861896
TI  - Hwangryunhaedoktang in adult patients with atopic dermatitis: a randomised,
      double-blind, placebo-controlled, two-centre trial--study protocol.
AB  - BACKGROUND: Atopic Dermatitis is a chronic relapsing eczematous skin disease with
      increasing prevalence and rising costs. It has a clear impact on a patient's
      quality of life. Many patients are worried about the use of usual care
      techniques, such as corticosteroids and antihistamine due to the widespread fear
      of adverse effects. Complementary and alternative medical approaches have been
      employed to relieve symptoms of Atopic Dermatitis. Hwangryunhaedoktang is among
      the most strongly preferred and widely used herbal medicines for Atopic
      Dermatitis in Korea, as it causes very few serious adverse effects.We aim to
      establish basic clinical efficacy and safety data for Hwangryunhaedoktang, which
      is approved as an herbal medication by the Korean Food and Drug Administration,
      in adult patients with Atopic Dermatitis. METHODS/DESIGNS: This study is a
      randomised, double blind, placebo-controlled, two-centre trial with two parallel
      arms (Hwangryunhaedoktang and a placebo). The diagnosis of Atopic Dermatitis will
      be made according to the criteria of Hanifin and Rajka by two different Oriental
      medicine doctors. We will include participants experiencing typical conditions of
      intermittent or continuous Atopic Eczema for six or more months. Participants
      will receive Hwangryunhaedoktang or a placebo-drug for eight weeks. The total
      duration of each arm is eleven weeks. Each participant will be examined for signs
      and symptoms of Atopic Dermatitis before and after taking medication. A follow-up
      to evaluate the maintenance of safety will be performed two weeks after the final
      administration of medication. DISCUSSION: This trial will utilize high quality
      trial methodologies in accordance with consolidated standards of reporting trials
      guidelines. It will provide evidence for the clinical efficacy and safety
      evaluation of Hwangryunhaedoktang in adult patients with Atopic Dermatitis.
      Moreover, we will also employ health-related quality of life questionnaires to
      assess the changes in quality of life.

PMID- 21861897
TI  - Obesity, diabetes and OSAS induce of sleep disorders: exercise as therapy.
AB  - Sleep is an integral part of good health. Sleep disorders and variations in sleep
      habits are associated with a low-grade inflammatory status, which may be either a
      cause or consequence of other conditions, including obesity, diabetes and
      cardiovascular disease. Several strategies are available to counteract these
      conditions including continuous positive airway pressure (CPAP), pharmacological
      and nutritional interventions, and even surgery. At present, our group is
      investigating the effect of chronic endurance exercise on sleep alterations.

PMID- 21861898
TI  - Determinants for HIV testing and counselling in Nairobi urban informal
      settlements.
AB  - BACKGROUND: Counselling and testing is important in HIV prevention and care.
      Majority of people in sub-Saharan Africa do not know their HIV status and are
      therefore unable to take steps to prevent infection or take up life prolonging
      anti-retroviral drugs in time if infected. This study aimed at exploring
      determinants of HIV testing and counselling in two Nairobi informal settlements.
      METHODS: Data are derived from a cross-sectional survey nested in an ongoing
      demographic surveillance system. A total of 3,162 individuals responded to the
      interview and out of these, 82% provided a blood sample which was tested using
      rapid test kits. The outcome of interest in this paper was HIV testing status in
      the past categorised as "never tested"; "client-initiated testing and counselling
      (CITC)" and provider-initiated testing and counselling (PITC). Multinomial
      logistic regression was used to identify determinants of HIV testing. RESULTS:
      Approximately 31% of all respondents had ever been tested for HIV through CITC,
      22% through PITC and 42% had never been tested but indicated willingness to test.
      Overall, 62% of females and 38% of males had ever been tested for HIV. Males were
      less likely to have had CITC (OR = 0.47; p value < 0.001) and also less likely to
      have had PITC (OR = 0.16; p value < 0.001) compared to females. Individuals aged
      20-24 years were more likely to have had either CITC or PITC compared to the
      other age groups. The divorced/separated/widowed were more likely (OR = 1.65; p
      value < 0.01) to have had CITC than their married counterparts, while the never
      married were less likely to have had either CITC or PITC. HIV positive
      individuals (OR = 1.60; p value < 0.01) and those who refused testing in the
      survey (OR = 1.39; p value < 0.05) were more likely to have had CITC compared to
      their HIV negative counterparts. CONCLUSION: Although the proportion of
      individuals ever tested in the informal settlements is similar to the national
      average, it remains low compared to that of Nairobi province especially among
      men. Key determinants of HIV testing and counselling include; gender, age,
      education level, HIV status and marital status. These factors need to be
      considered in efforts aimed at increasing participation in HIV testing.

PMID- 21861900
TI  - Using movies to teach professionalism to medical students.
AB  - BACKGROUND: Professionalism topics are usually not covered as a separate lesson
      within formal curriculum, but in subtler and less officially recognized
      educational activities, which makes them difficult to teach and assess.
      Interactive methods (e.g. movies) could be efficient teaching methods but are
      rarely studied. The aims of this study were: 1) to test the relevance and
      usefulness of movies in teaching professionalism to fourth year medical students
      and, 2) to assess the impact of this teaching method on students' attitudes
      towards some professionalism topics. METHOD: This was an education study with
      qualitative data analysis in a group of eleven fourth year medical students from
      the Medical School of University Maribor who attended an elective four month
      course on professionalism. There were 8 (66.7%) female students in the group. The
      mean age of the students was 21.9 +/- 0.9 years. The authors used students'
      written reports and oral presentations as the basis for qualitative analysis
      using thematic codes. RESULTS: Students recognised the following dimensions in
      the movie: communication, empathy, doctors' personal interests and palliative
      care. It also made them think about their attitudes towards life, death and
      dying. CONCLUSIONS: The controlled environment of movies successfully enables
      students to explore their values, beliefs, and attitudes towards features of
      professionalism without feeling that their personal integrity had been
      threatened. Interactive teaching methods could become an indispensible aid in
      teaching professionalism to new generations.

PMID- 21861899
TI  - A single amino acid change within the R2 domain of the VvMYB5b transcription
      factor modulates affinity for protein partners and target promoters selectivity.
AB  - BACKGROUND: Flavonoid pathway is spatially and temporally controlled during plant
      development and the transcriptional regulation of the structural genes is mostly
      orchestrated by a ternary protein complex that involves three classes of
      transcription factors (R2-R3-MYB, bHLH and WDR). In grapevine (Vitis vinifera
      L.), several MYB transcription factors have been identified but the interactions
      with their putative bHLH partners to regulate specific branches of the flavonoid
      pathway are still poorly understood. RESULTS: In this work, we describe the
      effects of a single amino acid substitution (R69L) located in the R2 domain of
      VvMYB5b and predicted to affect the formation of a salt bridge within the
      protein. The activity of the mutated protein (name VvMYB5b(L), the native protein
      being referred as VvMYB5b(R)) was assessed in different in vivo systems: yeast,
      grape cell suspensions, and tobacco. In the first two systems, VvMYB5b(L)
      exhibited a modified trans-activation capability. Moreover, using yeast two
      hybrid assay, we demonstrated that modification of VvMYB5b transcriptional
      properties impaired its ability to correctly interact with VvMYC1, a grape bHLH
      protein. These results were further substantiated by overexpression of VvMYB5b(R)
      and VvMYB5b(L) genes in tobacco. Flowers from 35S::VvMYB5b(L) transgenic plants
      showed a distinct phenotype in comparison with 35S::VvMYB5b(R) and the control
      plants. Finally, significant differences in transcript abundance of flavonoid
      metabolism genes were observed along with variations in pigments accumulation.
      CONCLUSIONS: Taken together, our findings indicate that VvMYB5b(L) is still able
      to bind DNA but the structural consequences linked to the mutation affect the
      capacity of the protein to activate the transcription of some flavonoid genes by
      modifying the interaction with its co-partner(s). In addition, this study
      underlines the importance of an internal salt bridge for protein conformation and
      thus for the establishment of protein-protein interactions between MYB and bHLH
      transcription factors. Mechanisms underlying these interactions are discussed and
      a model is proposed to explain the transcriptional activity of VvMYB5(L) observed
      in the tobacco model.

PMID- 21861901
TI  - Ignored adult primary hypothyroidism presenting chiefly with persistent ovarian
      cysts: a need for increased awareness.
AB  - BACKGROUND: Ovarian cysts are a common cause for gynecological surgery. However,
      some cysts are a direct result of endocrine disorders and do not require surgery.
      This report describes an unusual case in which persistent ovarian cysts are
      associated with primary hypothyroidism in a young woman. The data were collected
      by history-taking, physical examination, laboratory tests, ultrasound, magnetic
      resonance imaging and a histo-pathological study. In addition, the exons of the
      gene encoding the human follicle-stimulating hormone receptor were sequenced.
      DISCUSSION: The patient had markedly elevated levels of thyroid-stimulating
      hormone and follicle-stimulating hormone and an enlarged pituitary gland. After
      treatment with thyroid hormone replacement, regression of the enlarged pituitary
      and the ovarian cysts was observed. The possible mechanisms of the
      pathophysiology are discussed below. SUMMARY: It is necessary to consider
      hypothyroidism and other endocrine disorders in the differential diagnosis of
      adult patients with ovarian multiple cyst formation in order to prevent
      inadvertent ovarian surgery.

PMID- 21861902
TI  - Growth and weight status in treatment-naive 12-16 year old adolescents with
      alcohol use disorders in Cape Town, South Africa.
AB  - BACKGROUND: Heavy alcohol consumption during adolescence has many known harmful
      health and social consequences and is strongly associated with numerous health
      risk behaviours. The consequences of heavy alcohol use during adolescence on
      nutritional status, specifically growth and weight status are largely unknown at
      this time. METHODS: Substance use, anthropometric indices of growth and weight,
      dietary energy intake and physical activity in heavy drinking adolescents
      (meeting DSM-IV criteria for alcohol use disorders) and matched light/non
      drinking control adolescents were assessed. RESULTS: Lifetime alcohol dose,
      measured in standard drinks of alcohol, was orders of magnitude higher in
      adolescents with alcohol use disorders (AUDs) compared to controls. The AUDs
      group was selected to represent relatively 'pure' AUDs, with minimal other drug
      use and no psychiatric diagnoses. The growth and weight status of adolescents
      with AUDs were generally comparable to that of controls, and is in line with the
      growth and weight status of the South African adolescent population. A greater
      proportion of overweight/obese females was found in both groups, with this
      percentage tending to be greater, although not significantly so, in the AUDs
      group. Adolescent females with AUDs had increased odds of being overweight/obese
      compared to controls, after adjustment for smoking, physical activity and energy
      intake. CONCLUSION: Anthropometric indices of growth and weight status of
      participants in the Control and AUD groups were generally comparable. Female
      adolescents with AUDs may have an increased risk of being overweight/obese
      compared to adolescent females without AUDs. The presence of an AUD in our
      adolescent sample was associated with higher energy intake. Longitudinal studies
      are needed to elucidate the effects of heavy alcohol use on energy balance,
      growth and weight status in adolescents as they age. Nonetheless, the current
      study contributes to our understanding of the impacts of heavy alcohol
      consumption on important aspects of adolescent development.

PMID- 21861903
TI  - Efficacy of the motile sperm organelle morphology examination (MSOME) in
      predicting pregnancy after intrauterine insemination.
AB  - BACKGROUND: Although the motile sperm organelle morphology examination (MSOME)
      was developed merely as a selection criterion, its application as a method for
      classifying sperm morphology may represent an improvement in the evaluation of
      semen quality. The aim of this study was to determine the prognostic value of
      normal sperm morphology using MSOME with regard to clinical pregnancy (CP) after
      intrauterine insemination (IUI). METHODS: A total of 156 IUI cycles that were
      performed in 111 couples were prospectively analysed. Each subject received 75 IU
      of recombinant FSH every second day from the third day of the cycle. Beginning on
      the 10th day of the cycle, follicular development was monitored by vaginal
      ultrasound. When one or two follicles measuring at least 17 mm were observed,
      recombinant hCG was administered, and IUI was performed 12-14 h and 36-40 h after
      hCG treatment. Prior to the IUI procedure, sperm samples were analysed by MSOME
      at 8400* magnification using an inverted microscope that was equipped with
      DIC/Nomarski differential interference contrast optics. A minimum of 200 motile
      spermatozoa per semen sample were evaluated, and the percentage of normal
      spermatozoa in each sample was determined. RESULTS: Pregnancy occurred in 34 IUI
      cycles (CP rate per cycle: 21.8%, per patient: 30.6%). Based on the MSOME
      criteria, a significantly higher percentage of normal spermatozoa was found in
      the group of men in which the IUI cycles resulted in pregnancy (2.6+/-3.1%)
      compared to the group that did not achieve pregnancy (1.2+/-1.7%; P = 0.019).
      Logistic regression showed that the percentage of normal cells in the MSOME was a
      determining factor for the likelihood of clinical pregnancy (OR: 1.28; 95% CI:
      1.08 to 1.51; P = 0.003). The ROC curve revealed an area under the curve of 0.63
      and an optimum cut-off point of 2% of normal sperm morphology. At this cut-off
      threshold, using the percentage of normal sperm morphology by MSOME to predict
      pregnancy was 50% sensitive with a 40% positive predictive value and 79%
      specificity with an 85% negative predictive value. The efficacy of using the
      percentage of normal sperm morphology by MSOME in predicting pregnancy was 65%.
      CONCLUSIONS: The present findings support the use of high-magnification
      microscopy both for selecting spermatozoa and as a routine method for analysing
      semen before performing IUI.

PMID- 21861904
TI  - Current status of multiple antigen-presenting peptide vaccine systems:
      Application of organic and inorganic nanoparticles.
AB  - Many studies are currently investigating the development of safe and effective
      vaccines to prevent various infectious diseases. Multiple antigen-presenting
      peptide vaccine systems have been developed to avoid the adverse effects
      associated with conventional vaccines (i.e., live-attenuated, killed or
      inactivated pathogens), carrier proteins and cytotoxic adjuvants. Recently, two
      main approaches have been used to develop multiple antigen-presenting peptide
      vaccine systems: (1) the addition of functional components, e.g., T-cell
      epitopes, cell-penetrating peptides, and lipophilic moieties; and (2) synthetic
      approaches using size-defined nanomaterials, e.g., self-assembling peptides, non
      peptidic dendrimers, and gold nanoparticles, as antigen-displaying platforms.
      This review summarizes the recent experimental studies directed to the
      development of multiple antigen-presenting peptide vaccine systems.

PMID- 21861905
TI  - The Big Drink Debate: perceptions of the impact of price on alcohol consumption
      from a large scale cross-sectional convenience survey in north west England.
AB  - BACKGROUND: A large-scale survey was conducted in 2008 in north west England, a
      region with high levels of alcohol-related harm, during a regional 'Big Drink
      Debate' campaign. The aim of this paper is to explore perceptions of how alcohol
      consumption would change if alcohol prices were to increase or decrease. METHODS:
      A convenience survey of residents (>= 18 years) of north west England measured
      demographics, income, alcohol consumption in previous week, and opinions on
      drinking behaviour under two pricing conditions: low prices and discounts and
      increased alcohol prices (either 'decrease', 'no change' or 'increase').
      Multinomial logistic regression used three outcomes: 'completely elastic'
      (consider that lower prices increase drinking and higher prices decrease
      drinking); 'lower price elastic' (lower prices increase drinking, higher prices
      have no effect); and 'price inelastic' (no change for either). RESULTS: Of 22,780
      drinkers surveyed, 80.3% considered lower alcohol prices and discounts would
      increase alcohol consumption, while 22.1% thought raising prices would decrease
      consumption, making lower price elasticity only (i.e. lower prices increase
      drinking, higher prices have no effect) the most common outcome (62%). Compared
      to a high income/high drinking category, the lightest drinkers with a low income
      (adjusted odds ratio AOR = 1.78, 95% confidence intervals CI 1.38-2.30) or medium
      income (AOR = 1.88, CI 1.47-2.41) were most likely to be lower price elastic.
      Females were more likely than males to be lower price elastic (65% vs 57%) while
      the reverse was true for complete elasticity (20% vs 26%, P < 0.001).
      CONCLUSIONS: Lower pricing increases alcohol consumption, and the alcohol
      industry's continued focus on discounting sales encourages higher drinking
      levels. International evidence suggests increasing the price of alcohol reduces
      consumption, and one in five of the surveyed population agreed; more work is
      required to increase this agreement to achieve public support for policy change.
      Such policy should also recognise that alcohol is an addictive drug, and the
      population may be prepared to pay more to drink the amount they now feel they
      need.

PMID- 21861906
TI  - Metabolic changes in concussed American football players during the acute and
      chronic post-injury phases.
AB  - BACKGROUND: Despite negative neuroimaging findings many athletes display
      neurophysiological alterations and post-concussion symptoms that may be
      attributable to neurometabolic alterations. METHODS: The present study
      investigated the effects of sports concussion on brain metabolism using 1H-MR
      Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10
      concussed athletes of the same age (mean: 22.5 years) and education (mean: 16
      years) within both the acute and chronic post-injury phases. All athletes were
      scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI.
      RESULTS: Concussed athletes demonstrated neurometabolic impairment in prefrontal
      and motor (M1) cortices in the acute phase where NAA:Cr levels remained depressed
      relative to controls. There was some recovery observed in the chronic phase where
      Glu:Cr levels returned to those of control athletes; however, there was a
      pathological increase of m-I:Cr levels in M1 that was only present in the chronic
      phase. CONCLUSIONS: These results confirm cortical neurometabolic changes in the
      acute post-concussion phase as well as recovery and continued metabolic
      abnormalities in the chronic phase. The results indicate that complex
      pathophysiological processes differ depending on the post-injury phase and the
      neurometabolite in question.

PMID- 21861907
TI  - Activation of TRPA1 by membrane permeable local anesthetics.
AB  - BACKGROUND: Low concentrations of local anesthetics (LAs) suppress cellular
      excitability by inhibiting voltage-gated Na+ channels. In contrast, LAs at high
      concentrations can be excitatory and neurotoxic. We recently demonstrated that LA
      evoked activation of sensory neurons is mediated by the capsaicin receptor TRPV1,
      and, to a lesser extent by the irritant receptor TRPA1. LA-induced activation and
      sensitization of TRPV1 involves a domain that is similar, but not identical to
      the vanilloid-binding domain. Additionally, activation of TRPV1 by LAs involves
      PLC and PI(4,5)P2-signalling. In the present study we aimed to characterize
      essential structural determinants for LA-evoked activation of TRPA1. RESULTS:
      Recombinant rodent and human TRPA1 were expressed in HEK293t cells and
      investigated by means of whole-cell patch clamp recordings. The LA lidocaine
      activates TRPA1 in a concentration-dependent manner. The membrane impermeable
      lidocaine-derivative QX-314 is inactive when applied extracellularly. Lidocaine
      activated TRPA1-currents are blocked by the TRPA1-antagonist HC-030031. Lidocaine
      is also an inhibitor of TRPA1, an effect that is more obvious in rodent than in
      human TRPA1. This species-specific difference is linked to the pore region
      (transmembrane domain 5 and 6) as described for activation of TRPA1 by menthol.
      Unlike menthol-sensitivity however, lidocaine-sensitivity is not similarly
      determined by serine- and threonine-residues within TM5. Instead, intracellular
      cysteine residues known to be covalently bound by reactive TRPA1-agonists seem to
      mediate activation of TRPA1 by LAs. CONCLUSIONS: The structural determinants
      involved in activation of TRPA1 by LAs are disparate from those involved in
      activation by menthol or those involved in activation of TRPV1 by LAs.

PMID- 21861908
TI  - Long term life dissatisfaction and subsequent major depressive disorder and poor
      mental health.
AB  - BACKGROUND: Poor mental health, especially due to depression, is one of the main
      public health problems. Early indicators of poor mental health in general
      population are needed. This study examined the relationship between long-term
      life dissatisfaction and subsequent mental health, including major depressive
      disorder. METHOD: Health questionnaires were sent to a randomly selected
      population-based sample in 1998 and repeated in 1999 and 2001. In 2005, a
      clinically studied sub-sample (n = 330) was composed of subjects with (n = 161)
      or without (n = 169) repeatedly reported adverse mental symptoms at all three
      previous data collection times. Clinical symptom assessments were performed with
      several psychometric scales: life satisfaction (LS), depression (HDRS, BDI),
      hopelessness (HS), mental distress (GHQ), dissociative experiences (DES), and
      alexithymia (TAS). The long-term life dissatisfaction burden was calculated by
      summing these life satisfaction scores in 1998, 1999, 2001 and dividing the sum
      into tertiles. Psychiatric diagnoses were confirmed by SCID-I for DSM-IV in 2005.
      Logistic regression analyses were performed to assess the studied relationship.
      RESULTS: The previous life dissatisfaction burden associated with adverse socio
      demographic, life style and clinical factors. In adjusted logistic regression
      analyses, it was independently and strongly associated with subsequent major
      depressive disorder in 2005, even when the concurrent LS score in 2005 was
      included in the model. Excluding those with reported major depressive disorder in
      1999 did not alter this finding. LIMITATIONS: MDD in 1999 was based on self
      reports and not on structured interview and LS data in 2001-2005 was not
      available. CONCLUSIONS: The life satisfaction burden is significantly related to
      major depressive disorder and poor mental health, both in cross-sectional and
      longitudinal settings.

PMID- 21861909
TI  - Effects of shared medical appointments on quality of life and cost-effectiveness
      for patients with a chronic neuromuscular disease. Study protocol of a randomized
      controlled trial.
AB  - BACKGROUND: Shared medical appointments are a series of one-to-one doctor-patient
      contacts, in presence of a group of 6-10 fellow patients. This group visits
      substitute the annual control visits of patients with the neurologist. The same
      items attended to in a one-to-one appointment are addressed. The possible
      advantages of a shared medical appointment could be an added value to the present
      management of neuromuscular patients. The currently problem-focused one-to-one
      out-patient visits often leave little time for the patient's psychosocial needs,
      patient education, and patient empowerment. METHODS/DESIGN: A randomized,
      prospective controlled study (RCT) with a follow up of 6 months will be conducted
      to evaluate the clinical and cost-effectiveness of shared medical appointments
      compared to usual care for 300 neuromuscular patients and their partners at the
      Radboud University Nijmegen Medical Center. Every included patient will be
      randomly allocated to one of the two study arms. This study has been reviewed and
      approved by the medical ethics committee of the region Arnhem-Nijmegen, The
      Netherlands. The primary outcome measure is quality of life as measured by the EQ
      5D, SF-36 and the Individualized neuromuscular Quality of Life Questionnaire. The
      primary analysis will be an intention-to-treat analysis on the area under the
      curve of the quality of life scores. A linear mixed model will be used with
      random factor group and fixed factors treatment, baseline score and type of
      neuromuscular disease. For the economic evaluation an incremental cost
      effectiveness analysis will be conducted from a societal perspective, relating
      differences in costs to difference in health outcome. Results are expected in
      2012. DISCUSSION: This study will be the first randomized controlled trial which
      evaluates the effect of shared medical appointments versus usual care for
      neuromuscular patients. This will enable to determine if there is additional
      value of shared medical appointments to the current therapeutical spectrum. When
      this study shows that group visits produce the alleged benefits, this may help to
      increase the acceptance of this innovative and creative way of using one of the
      most precious resources in health care more efficiently: time. TRIAL
      REGISTRATION: DutchTrial Register http://www.trialregister.nlNTR1412.

PMID- 21861910
TI  - Preliminary study of the antioxidant properties of flowers and roots of
      Pyrostegia venusta (Ker Gawl) Miers.
AB  - BACKGROUND: Free radical stress leads to tissue injury and can eventually to
      arthritis, atherosclerosis, diabetes mellitus, neurodegenerative diseases and
      carcinogenesis. Several studies are ongoing worldwide to find natural
      antioxidants of plant origin. We assessed the in-vitro antioxidant activities and
      screened the phytochemical constituents of methanolic extracts of Pyrostegia
      venusta (Ker Gawl) Miers. METHODS: We evaluated the antioxidant potential and
      phytochemical constituents of P. venusta using 1,1-Diphenyl-2-picrylhydrazyl
      (DPPH), 2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric
      reducing antioxidant power (FRAP) assays. Gas chromatography-mass spectroscopy
      (GC-MS) studies were also undertaken to assess the phytochemical composition of
      the flower extracts. RESULTS: Phytochemical analyses revealed the presence of
      terpenoids, alkaloids, tannins, steroids, and saponins. The reducing ability of
      both extracts was in the range (in MUm Fe(II)/g) of 112.49-3046.98 compared with
      butylated hydroxytoluene (BHT; 63.56 +/- 2.62), catechin (972.02 +/- 0.72 MUm)
      and quercetin 3208.27 +/- 31.29. A significant inhibitory effect of extracts of
      flowers (IC50 = 0.018 +/- 0.69 mg/ml) and roots (IC50 = 0.026 +/- 0.94 mg/ml) on
      ABTS free radicals was detected. The antioxidant activity of the extracts of
      flowers (95%) and roots (94%) on DPPH radicals was comparable with that of
      ascorbic acid (98.9%) and BHT (97.6%). GC-MS study revealed the presence of
      myoinositol, hexadecanoic acid, linoleic acid, palmitic acid and oleic acid in
      the flower extracts. CONCLUSION: These data suggest that P. venusta is a natural
      source of antioxidants. The extracts of flowers and roots of P. venusta contain
      significant amounts of phytochemicals with antioxidative properties and could
      serve as inhibitors or scavengers of free radicals. P. venusta could be exploited
      as a potential source for plant-based pharmaceutical products. These results
      could form a sound basis for further investigation in the potential discovery of
      new natural bioactive compounds.

PMID- 21861912
TI  - The future of medical diagnostics: review paper.
AB  - While histopathology of excised tissue remains the gold standard for diagnosis,
      several new, non-invasive diagnostic techniques are being developed. They rely on
      physical and biochemical changes that precede and mirror malignant change within
      tissue. The basic principle involves simple optical techniques of tissue
      interrogation. Their accuracy, expressed as sensitivity and specificity, are
      reported in a number of studies suggests that they have a potential for cost
      effective, real-time, in situ diagnosis.We review the Third Scientific Meeting of
      the Head and Neck Optical Diagnostics Society held in Congress Innsbruck,
      Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual
      Scientific Meeting was held in association with the International Photodynamic
      Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The
      aim was to enhance the interdisciplinary aspects of optical diagnostics and other
      photodynamic applications. The meeting included 2 sections: oral communication
      sessions running in parallel to the IPA programme and poster presentation
      sessions combined with the IPA and EPPM posters sessions.

PMID- 21861913
TI  - Thymoma calcification: is it clinically meaningful?
AB  - Among anterior mediastinal lesions, thymoma is the most common. Thymomas are
      tumors of thymic epithelial cell origin that are distinguished by inconsistent
      histological and biologic behavior. Chest imaging studies typically show a round
      or lobulated tumor in the anterior mediastinum. Calcifications in thymomas are
      classically punctuate or amorphous, positioned within the lesion. Chest computed
      tomography (CT) features suggesting higher risk thymoma consist of tumor
      heterogeneity, vascular involvement, lobulation, pulmonary nodules,
      lymphadenopathy, and pleural manifestations. Imaging findings have an imperfect
      ability to predict stage and prognosis for thymoma patients. Our objective is to
      highlight the clinical implications of thymoma calcifications on the diagnosis,
      clinical manifestation and prognosis. A pubmed and google search was performed
      using the following words: thymoma calcification, calcified thymus, mediastinal
      calcification, anterior mediastinal calcification, and calcified thymoma. After
      reviewing 370 articles, 32 eligible articles describing thymoma calcifications
      were found and included in this review. Although the presence of thymus
      calcifications was more common in patients with invasive thymomas, they were
      present in significant portion of non-invasive thymomas. The presence of
      calcifications was not a significant factor in differentiating between benign and
      malignant thymoma. As a result, the type, location, size or other characteristics
      of thymus gland calcifications were not relevant features in clinical and
      radiologic diagnosis of thymoma. The histopathological diagnosis is still the
      only possible way to confirm the neoplastic nature of thymoma. All types of
      thymomas should be evaluated and managed independently of the presence of
      calcifications.

PMID- 21861911
TI  - What is the value and impact of quality and safety teams? A scoping review.
AB  - BACKGROUND: The purpose of this study was to conduct a scoping review of the
      literature about the establishment and impact of quality and safety team
      initiatives in acute care. METHODS: Studies were identified through electronic
      searches of Medline, Embase, CINAHL, PsycINFO, ABI Inform, Cochrane databases.
      Grey literature and bibliographies were also searched. Qualitative or
      quantitative studies that occurred in acute care, describing how quality and
      safety teams were established or implemented, the impact of teams, or the
      barriers and/or facilitators of teams were included. Two reviewers independently
      extracted data on study design, sample, interventions, and outcomes. Quality
      assessment of full text articles was done independently by two reviewers. Studies
      were categorized according to dimensions of quality. RESULTS: Of 6,674 articles
      identified, 99 were included in the study. The heterogeneity of studies and
      results reported precluded quantitative data analyses. Findings revealed limited
      information about attributes of successful and unsuccessful team initiatives,
      barriers and facilitators to team initiatives, unique or combined contribution of
      selected interventions, or how to effectively establish these teams. CONCLUSIONS:
      Not unlike systematic reviews of quality improvement collaboratives, this broad
      review revealed that while teams reported a number of positive results, there are
      many methodological issues. This study is unique in utilizing traditional quality
      assessment and more novel methods of quality assessment and reporting of results
      (SQUIRE) to appraise studies. Rigorous design, evaluation, and reporting of
      quality and safety team initiatives are required.

PMID- 21861914
TI  - Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in
      chronic obstructive pulmonary disease patients: a randomized controlled trial.
AB  - BACKGROUND: The use of noninvasive intermittent positive pressure ventilation
      (NIPPV) in chronic obstructive pulmonary disease (COPD) patients with chronic
      hypercapnic respiratory failure remains controversial as long-term data are
      almost lacking. The aim was to compare the outcome of 2-year home-based nocturnal
      NIPPV in addition to rehabilitation (NIPPV + PR) with rehabilitation alone (PR)
      in COPD patients with chronic hypercapnic respiratory failure. METHODS: Sixty-six
      patients could be analyzed for the two-year home-based follow-up period.
      Differences in change between the NIPPV + PR and PR group were assessed by a
      linear mixed effects model with a random effect on the intercept, and adjustment
      for baseline values. The primary outcome was health-related quality of life
      (HRQoL); secondary outcomes were mood state, dyspnea, gas exchange, functional
      status, pulmonary function, and exacerbation frequency. RESULTS: Although the
      addition of NIPPV did not significantly improve the Chronic Respiratory
      Questionnaire compared to rehabilitation alone (mean difference in change between
      groups -1.3 points (95% CI: -9.7 to 7.4)), the addition of NIPPV did improve
      HRQoL assessed with the Maugeri Respiratory Failure questionnaire (-13.4% (-22.7
      to -4.2; p = 0.005)), mood state (Hospital Anxiety and Depression scale -4.0
      points (-7.8 to 0.0; p = 0.05)), dyspnea (Medical Research Council -0.4 points (
      0.8 to -0.0; p = 0.05)), daytime arterial blood gases (PaCO2 -0.4 kPa (-0.8 to 
      0.2; p = 0.01); PaO2 0.8 kPa (0.0 to 1.5; p = 0.03)), 6-minute walking distance
      (77.3 m (46.4 to 108.0; p < 0.001)), Groningen Activity and Restriction scale (
      3.8 points (-7.4 to -0.4; p = 0.03)), and forced expiratory volume in 1 second
      (115 ml (19 to 211; p = 0.019)). Exacerbation frequency was not changed.
      CONCLUSIONS: The addition of NIPPV to pulmonary rehabilitation for 2 years in
      severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL,
      mood, dyspnea, gas exchange, exercise tolerance and lung function decline. The
      benefits increase further with time. TRIAL REGISTRATION: ClinicalTrials.Gov (ID
      NCT00135538).

PMID- 21861916
TI  - Necrotizing sialometaplasia as a cause of a non-ulcerated nodule in the hard
      palate: a case report.
AB  - INTRODUCTION: Necrotizing sialometaplasia is a benign, self-limiting and rare
      inflammatory disease which, on clinical and histological examination, mimics
      malignant neoplasms. CASE REPORT: We report the case of a healthy 25-year-old
      Caucasian woman with a three-week history of a painless lump on her hard palate.
      Oral examination revealed a nodule consisting of two lobules on the right side
      that measured 2.5 cm. Her mucosa was normal in color and a fluctuant area was
      detected in the posterior region upon palpation. Our patient was submitted to
      incisional biopsy and histopathological examination. The histological diagnosis
      was necrotizing sialometaplasia. The lesion had healed spontaneously after 30
      days, with observed signs of involution of the nodule. CONCLUSION:
      Histopathological examination is necessary for the diagnosis of necrotizing
      sialometaplasia because the clinical features of this condition can mimic other
      diseases, particularly malignant neoplasms.

PMID- 21861915
TI  - Lentiviral gene transfer into the dorsal root ganglion of adult rats.
AB  - BACKGROUND: Lentivector-mediated gene delivery into the dorsal root ganglion
      (DRG) is a promising method for exploring pain pathophysiology and for genetic
      treatment of chronic neuropathic pain. In this study, a series of modified
      lentivector particles with different cellular promoters, envelope glycoproteins,
      and viral accessory proteins were generated to evaluate the requirements for
      efficient transduction into neuronal cells in vitro and adult rat DRG in vivo.
      RESULTS: In vitro, lentivectors expressing enhanced green fluorescent protein
      (EGFP) under control of the human elongation factor 1alpha (EF1alpha) promoter
      and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV
      G) envelope exhibited the best performance in the transfer of EGFP into an
      immortalized DRG sensory neuron cell line at low multiplicities of infection
      (MOIs), and into primary cultured DRG neurons at higher MOIs. In vivo, injection
      of either first or second-generation EF1alpha-EGFP lentivectors directly into
      adult rat DRGs led to transduction rates of 19 +/- 9% and 20 +/- 8% EGFP-positive
      DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells
      included a full range of neuronal phenotypes, including myelinated neurons as
      well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons.
      CONCLUSION: VSV-G pseudotyped lentivectors containing the human elongation factor
      1alpha (EF1alpha)-EGFP expression cassette demonstrated relatively efficient
      transduction to sensory neurons following direct injection into the DRG. These
      results clearly show the potential of lentivectors as a viable system for
      delivering target genes into DRGs to explore basic mechanisms of neuropathic
      pain, with the potential for future clinical use in treating chronic pain.

PMID- 21861917
TI  - Protective effect of quercetin against oxidative stress caused by dimethoate in
      human peripheral blood lymphocytes.
AB  - BACKGROUND: The aim of this study is to investigate the effect of quercetin in
      alleviating the cytotoxic effects of Dimethoate in human peripheral blood
      lymphocytes. METHODS: Lymphocytes were divided into too groups. The first group,
      lymphocytes were incubated for 4 h at 37 degrees C with different concentrations
      (0, 40, 60 and 100 mM) of Dimethoate. The second group was preincubated with
      quercetin for 30 min and followed by Dim incubation for 4 h at 37 degrees C.
      RESULTS: Following in vitro incubation, Dimethoate caused a significant increase
      in malondialdehyde levels, a significant decrease in thiol levels, as well as a
      significant increase in superoxide dismutase, and catalase activities in
      lymphocytes at different concentrations. Quercetin pretreated lymphocytes showed
      a significant protection against the cytotoxic effects inducted by Dimethoate on
      the studied parameters. CONCLUSION: In conclusion, antioxidant quercetin could
      protect against Dimethoate-induced oxidative stress by decreasing lipid
      peroxidation, protein oxidation and increasing superoxide dismutase and catalase
      activities in human lymphocytes.

PMID- 21861919
TI  - Failure of functional imaging with gallium-68-DOTA-D-Phe1-Tyr3-octreotide
      positron emission tomography to localize the site of ectopic adrenocorticotropic
      hormone secretion: a case report.
AB  - INTRODUCTION: The diagnostic efficacy of biochemical and imaging modalities for
      investigating the causes of Cushing's syndrome are limited. We report a case
      demonstrating the limitations of these modalities, especially the inability of
      functional imaging to help localize the site of ectopic adrenocorticotropic
      hormone secretion. CASE PRESENTATION: A 37-year-old Arabian woman presented with
      12 months of progressive Cushing's syndrome-like symptoms. Biochemical evaluation
      confirmed adrenocorticotropic hormone -dependent Cushing's syndrome. However, the
      anatomical site of her excess adrenocorticotropic hormone secretion was not
      clearly delineated by further investigations. Magnetic resonance imaging of our
      patient's pituitary gland failed to demonstrate the presence of an adenoma.
      Spiral computed tomography of her chest only revealed the presence of a non
      specific 7 mm lesion in her left inferobasal lung segment. Functional imaging,
      including a positron emission tomography scan using 18-fluorodeoxyglucose and
      gallium-68-DOTA-D-Phe1-Tyr3-octreotide, also failed to show increased metabolic
      activity in the lung lesion or in her pituitary gland. Our patient was commenced
      on medical treatment with ketoconazole and metyrapone to control the clinical
      features associated with her excess cortisol secretion. Despite initial
      normalization of her urinary free cortisol excretion rate, levels began to rise
      eight months after commencement of medical treatment. Repeated imaging of her
      pituitary gland, chest and pelvis again failed to clearly localize a source of
      her excess adrenocorticotropic hormone secretion. The bronchial nodule was stable
      in size on serial imaging and repeatedly reported as having a nonspecific
      appearance of a small granuloma or lymph node. We re-explored the treatment
      options and endorsed our patient's favored choice of resection of the bronchial
      nodule, especially given that her symptoms of cortisol excess were difficult to
      control and refractory. Subsequently, our patient had the bronchial nodule
      resected. The histological appearance of the lesion was consistent with that of a
      carcinoid tumor and immunohistochemical analysis revealed that the tumor stained
      strongly positive for adrenocorticotropic hormone. Furthermore, removal of the
      lung lesion resulted in a normalization of our patient's 24-hour urinary free
      cortisol excretion rate and resolution of her symptoms and signs of
      hypercortisolemia. CONCLUSION: This case report demonstrates the complexities and
      challenges in diagnosing the causes of adrenocorticotropic hormone -dependent
      Cushing's syndrome. Functional imaging may not always localize the site of
      ectopic adrenocorticotropic hormone secretion.

PMID- 21861918
TI  - The Public Goods Hypothesis for the evolution of life on Earth.
AB  - It is becoming increasingly difficult to reconcile the observed extent of
      horizontal gene transfers with the central metaphor of a great tree uniting all
      evolving entities on the planet. In this manuscript we describe the Public Goods
      Hypothesis and show that it is appropriate in order to describe biological
      evolution on the planet. According to this hypothesis, nucleotide sequences
      (genes, promoters, exons, etc.) are simply seen as goods, passed from organism to
      organism through both vertical and horizontal transfer. Public goods sequences
      are defined by having the properties of being largely non-excludable (no organism
      can be effectively prevented from accessing these sequences) and non-rival (while
      such a sequence is being used by one organism it is also available for use by
      another organism). The universal nature of genetic systems ensures that such non
      excludable sequences exist and non-excludability explains why we see a myriad of
      genes in different combinations in sequenced genomes. There are three features of
      the public goods hypothesis. Firstly, segments of DNA are seen as public goods,
      available for all organisms to integrate into their genomes. Secondly, we expect
      the evolution of mechanisms for DNA sharing and of defense mechanisms against DNA
      intrusion in genomes. Thirdly, we expect that we do not see a global tree-like
      pattern. Instead, we expect local tree-like patterns to emerge from the
      combination of a commonage of genes and vertical inheritance of genomes by cell
      division. Indeed, while genes are theoretically public goods, in reality, some
      genes are excludable, particularly, though not only, when they have variant
      genetic codes or behave as coalition or club goods, available for all organisms
      of a coalition to integrate into their genomes, and non-rival within the club. We
      view the Tree of Life hypothesis as a regionalized instance of the Public Goods
      hypothesis, just like classical mechanics and euclidean geometry are seen as
      regionalized instances of quantum mechanics and Riemannian geometry respectively.
      We argue for this change using an axiomatic approach that shows that the Public
      Goods hypothesis is a better accommodation of the observed data than the Tree of
      Life hypothesis.

PMID- 21861920
TI  - A randomised controlled trial to prevent hospital readmissions and loss of
      functional ability in high risk older adults: a study protocol.
AB  - BACKGROUND: Older people have higher rates of hospital admission than the general
      population and higher rates of readmission due to complications and falls. During
      hospitalisation, older people experience significant functional decline which
      impairs their future independence and quality of life. Acute hospital services
      comprise the largest section of health expenditure in Australia and prevention or
      delay of disease is known to produce more effective use of services. Current
      models of discharge planning and follow-up care, however, do not address the need
      to prevent deconditioning or functional decline. This paper describes the
      protocol of a randomised controlled trial which aims to evaluate innovative
      transitional care strategies to reduce unplanned readmissions and improve
      functional status, independence, and psycho-social well-being of community-based
      older people at risk of readmission. METHODS/DESIGN: The study is a randomised
      controlled trial. Within 72 hours of hospital admission, a sample of older adults
      fitting the inclusion/exclusion criteria (aged 65 years and over, admitted with a
      medical diagnosis, able to walk independently for 3 meters, and at least one risk
      factor for readmission) are randomised into one of four groups: 1) the usual care
      control group, 2) the exercise and in-home/telephone follow-up intervention
      group, 3) the exercise only intervention group, or 4) the in-home/telephone
      follow-up only intervention group. The usual care control group receive usual
      discharge planning provided by the health service. In addition to usual care, the
      exercise and in-home/telephone follow-up intervention group receive an
      intervention consisting of a tailored exercise program, in-home visit and 24 week
      telephone follow-up by a gerontic nurse. The exercise only and in-home/telephone
      follow-up only intervention groups, in addition to usual care receive only the
      exercise or gerontic nurse components of the intervention respectively. Data
      collection is undertaken at baseline within 72 hours of hospital admission, 4
      weeks following hospital discharge, 12 weeks following hospital discharge, and 24
      weeks following hospital discharge. Outcome assessors are blinded to group
      allocation. Primary outcomes are emergency hospital readmissions and health
      service use, functional status, psychosocial well-being and cost effectiveness.
      DISCUSSION: The acute hospital sector comprises the largest component of health
      care system expenditure in developed countries, and older adults are the most
      frequent consumers. There are few trials to demonstrate effective models of
      transitional care to prevent emergency readmissions, loss of functional ability
      and independence in this population following an acute hospital admission. This
      study aims to address that gap and provide information for future health service
      planning which meets client needs and lowers the use of acute care services.
      TRIAL REGISTRATION NO: Australian & New Zealand Clinical Trials Registry
      ACTRN12608000202369.

PMID- 21861921
TI  - The major leucyl aminopeptidase of Trypanosoma cruzi (LAPTc) assembles into a
      homohexamer and belongs to the M17 family of metallopeptidases.
AB  - BACKGROUND: Pathogens depend on peptidase activities to accomplish many
      physiological processes, including interaction with their hosts, highlighting
      parasitic peptidases as potential drug targets. In this study, a major leucyl
      aminopeptidolytic activity was identified in Trypanosoma cruzi, the aetiological
      agent of Chagas disease. RESULTS: The enzyme was isolated from epimastigote forms
      of the parasite by a two-step chromatographic procedure and associated with a
      single 330-kDa homohexameric protein as determined by sedimentation velocity and
      light scattering experiments. Peptide mass fingerprinting identified the enzyme
      as the predicted T. cruzi aminopeptidase EAN97960. Molecular and enzymatic
      analysis indicated that this leucyl aminopeptidase of T. cruzi (LAPTc) belongs to
      the peptidase family M17 or leucyl aminopeptidase family. LAPTc has a strong
      dependence on neutral pH, is mesophilic and retains its oligomeric form up to 80
      degrees C. Conversely, its recombinant form is thermophilic and requires alkaline
      pH. CONCLUSIONS: LAPTc is a 330-kDa homohexameric metalloaminopeptidase expressed
      by all T. cruzi forms and mediates the major parasite leucyl aminopeptidolytic
      activity. Since biosynthetic pathways for essential amino acids, including
      leucine, are lacking in T. cruzi, LAPTc could have a function in nutritional
      supply.

PMID- 21861922
TI  - Reversal of TMS-induced motor twitch by training is associated with a reduction
      in excitability of the antagonist muscle.
AB  - BACKGROUND: A single session of isolated repetitive movements of the thumb can
      alter the response to transcranial magnetic stimulation (TMS), such that the
      related muscle twitch measured post-training occurs in the trained direction.
      This response is attributed to transient excitability changes in primary motor
      cortex (M1) that form the early part of learning. We investigated; (1) whether
      this phenomenon might occur for movements at the wrist, and (2) how specific TMS
      activation patterns of opposing muscles underlie the practice-induced change in
      direction. METHODS: We used single-pulse suprathreshold TMS over the M1 forearm
      area, to evoke wrist movements in 20 healthy subjects. We measured the
      preferential direction of the TMS-induced twitch in both the sagittal and coronal
      plane using an optical goniometer fixed to the dorsum of the wrist, and recorded
      electromyographic (EMG) activity from the flexor carpi radialis (FCR) and
      extensor carpi radialis (ECR) muscles. Subjects performed gentle voluntary
      movements, in the direction opposite to the initial twitch for 5 minutes at 0.2
      Hz. We collected motor evoked potentials (MEPs) elicited by TMS at baseline and
      for 10 minutes after training. RESULTS: Repetitive motor training was sufficient
      for TMS to evoke movements in the practiced direction opposite to the original
      twitch. For most subjects the effect of the newly-acquired direction was retained
      for at least 10 minutes before reverting to the original. Importantly, the
      direction change of the movement was associated with a significant decrease in
      MEP amplitude of the antagonist to the trained muscle, rather than an increase in
      MEP amplitude of the trained muscle. CONCLUSIONS: These results demonstrate for
      the first time that a TMS-twitch direction change following a simple practice
      paradigm may result from reduced corticospinal drive to muscles antagonizing the
      trained direction. Such findings may have implications for training paradigms in
      neurorehabilitation.

PMID- 21861923
TI  - The determinants of stroke phenotypes were different from the predictors (CHADS2
      and CHA2DS2-VASc) of stroke in patients with atrial fibrillation: a comprehensive
      approach.
AB  - BACKGROUND: Atrial fibrillation (AF) is a leading cause of fatal ischemic stroke.
      It was recently reported that international normalized ratio (INR) levels were
      associated with infarct volumes. However, factors other than INR levels that
      affect stroke phenotypes are largely unknown. Therefore, we evaluated the
      determinants of stroke phenotypes (pattern and volume) among patients with AF who
      were not adequately anticoagulated. METHODS: We analyzed data pertaining to
      consecutive AF patients admitted over a 6-year period with acute MCA territory
      infarcts. We divided the patients according to DWI (diffusion-weighted imaging)
      lesion volumes and patterns, and the relationship between stroke predictors (the
      CHADS2 and CHA2DS2-VASc score), systemic, and local factors and each stroke
      phenotype were then evaluated. RESULTS: The stroke phenotypes varied among 231
      patients (admission INR median 1.06, interquartile range (IQR) 1.00-1.14).
      Specifically, (1) the DWI lesion volumes ranged from 0.04-338.62 ml (median 11.86
      ml; IQR, 3.07-44.20 ml) and (2) 46 patients had a territorial infarct pattern,
      118 had a lobar/deep pattern and 67 had a small scattered pattern. Multivariate
      testing revealed that the CHADS2 and CHA2DS2-VASc score were not related to
      either stroke phenotype. Additionally, the prior use of antiplatelet agents was
      not related to the stroke phenotypes. Congestive heart failure and diastolic
      dysfunction were not associated with stroke phenotypes. CONCLUSIONS: The results
      of this study indicated that the determinants of stroke phenotypes were different
      from the predictors (i.e., CHADS2 and CHA2DS2-VASc score) of stroke in patients
      with AF.

PMID- 21861925
TI  - Does the principle of minimum work apply at the carotid bifurcation: a
      retrospective cohort study.
AB  - BACKGROUND: There is recent interest in the role of carotid bifurcation anatomy,
      geometry and hemodynamic factors in the pathogenesis of carotid artery
      atherosclerosis. Certain anatomical and geometric configurations at the carotid
      bifurcation have been linked to disturbed flow. It has been proposed that
      vascular dimensions are selected to minimize energy required to maintain blood
      flow, and that this occurs when an exponent of 3 relates the radii of parent and
      daughter arteries. We evaluate whether the dimensions of bifurcation of the
      extracranial carotid artery follow this principle of minimum work. METHODS: This
      study involved subjects who had computed tomographic angiography (CTA) at our
      institution between 2006 and 2007. Radii of the common, internal and external
      carotid arteries were determined. The exponent was determined for individual
      bifurcations using numerical methods and for the sample using nonlinear
      regression. RESULTS: Mean age for 45 participants was 56.9 +/- 16.5 years with 26
      males. Prevalence of vascular risk factors was: hypertension--48%, smoking--23%,
      diabetes--16.7%, hyperlipidemia--51%, ischemic heart disease--18.7%.The value of
      the exponent ranged from 1.3 to 1.6, depending on estimation methodology.
      CONCLUSIONS: The principle of minimum work (defined by an exponent of 3) may not
      apply at the carotid bifurcation. Additional factors may play a role in the
      relationship between the radii of the parent and daughter vessels.

PMID- 21861924
TI  - Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces
      pastorianus activate peroxisome proliferator-activated receptors.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are ligand
      activated transcription factors that regulate lipid and glucose metabolism.
      PPARalpha is highly expressed in the liver and controls genes involved in lipid
      catabolism. We previously reported that synthetic sphingolipid analogs, part of
      which contains shorter-length fatty acid chains than natural sphingolipids,
      stimulated the transcriptional activities of PPARs. Sphingosine and
      dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and
      dihydroceramide are major ceramide species in mammals. In contrast,
      phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and
      phytoceramide exist in particular tissues such as the epidermis in mammals, and
      involvement of ceramide species in PPARbeta activation in cultured keratinocytes
      has been reported. The purpose of the present study is to investigate whether
      natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases
      activate PPARs as PPAR agonists. METHOD: Lipids of brewer's yeast contain PHS-
      and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted
      from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified
      and quantified. To assess the effects of sphingolipids on PPAR activation,
      luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2)
      cells were transfected with expression vectors for PPARs and retinoid *
      receptors, and PPAR responsive element reporter vector. When indicated, the
      PPAR/Gal4 chimera system was performed to enhance the credibility of experiments.
      Sphingolipids were added to the cells and the dual luciferase reporter assay was
      performed to determine the transcriptional activity of PPARs. RESULTS: We
      observed that phytoceramide increased the transcriptional activities of PPARs
      significantly, whereas ceramide and dihydroceramide did not change PPAR
      activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera
      receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or
      authentic PHS or DHS increased PPAR-dependent transcription. Additionally,
      phytoceramide stimulated PPARalpha activity in HepG2 hepatocytes, suggesting that
      phytoceramide activates genes regulated by PPARalpha. CONCLUSIONS: Phytoceramide
      and yeast-derived sphingoid bases activate PPARs, whereas ceramide and
      dihydroceramide do not change the PPAR activity. The present findings suggest
      that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.

PMID- 21861926
TI  - Expression and characterization of UL16 gene from duck enteritis virus.
AB  - BACKGROUND: Previous studies have indicated that the UL16 protein and its
      homologs from herpesvirus were conserved and played similar roles in viral DNA
      packaging, virion assembly, budding, and egress. However, there was no report on
      the UL16 gene product of duck enteritis virus (DEV). In this study, we analyzed
      the amino acid sequence of UL16 using bioinformatics tools and expressed in
      Escherichia coli Rosetta (DE3) induced by isopropy1-beta-D-thiogalactopyranoside
      (IPTG). The recombinant protein was produced, purified using a Ni-NTA column and
      used to generate the polyclonal antibody against UL16. The intracellular
      distribution of the DEV UL16 product was carried out using indirect
      immunofluorescence assay. RESULTS: In our study, UL16 gene of DEV was composed of
      1089 nucleotides, which encoded 362 amino acids. Multiple sequence alignment
      suggested that the UL16 gene was highly conserved in herpesvirus family. The UL16
      gene was cloned into a pET prokaryotic expression vector and transformed into
      Escherichia coli Rossetta (DE3) induced by IPTG. A 60kDa fusion protein band
      corresponding to the predicted size was produced on the SDS-PAGE, purified using
      a Ni-NTA column. Anti-UL16 polyclonal sera was prepared by immunizing rabbits,
      and reacted with a band in the IPTG induced cell lysates with an apparent
      molecular mass of 60 kDa. In vivo expression of the UL16 protein in DEV infected
      duck embryo fibroblast cells (DEFs) was localized mostly around perinuclear
      cytoplasmic area and in cytosol using indirect immunofluorescence assay.
      CONCLUSIONS: The UL16 gene of DEV was successfully cloned, expressed and detected
      in DEV infected DEFs for the first time. The UL16 protein localized mostly around
      perinuclear cytoplasmic area and in cytosol in DEV infected DEFs. DEV UL16 shared
      high similarity with UL16 family members, indicating that DEV UL16 many has
      similar function with its homologs. All these results may provide some insight
      for further research about full characterizations and functions of the DEV UL16.

PMID- 21861927
TI  - Hypothalamic inflammation is reversed by endurance training in anorectic
      cachectic rats.
AB  - AIM: We tested the effects of a cancer cachexia-anorexia sydrome upon the balance
      of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or
      trained tumour-bearing (Walker-256 carcinosarcoma) rats. METHODS: Animals were
      randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST), and
      sedentary pair-fed (SPF) groups or, exercised control (EC), exercised tumour
      bearing (ET) and exercised pair-fed (EPF) groups. Trained rats ran on a treadmill
      (60%VO2max) for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin
      and cytokine (TNF-alpha, IL1beta) levels in the hypothalamus. RESULTS: The
      cumulative food intake and serum leptin concentration were reduced in ST compared
      to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT) was
      increased in SPF in comparison with SC and ST, and in the mesenteric adipose
      tissue (MEAT) the same parameter was decreased in ST in relation to SC. Leptin
      levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise
      training was also able to reduce tumour weight when compared to ST group. In the
      hypothalamus, IL-1beta and IL-10 gene expression was higher in ST than in SC and
      SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-alpha and IL
      1beta, p < 0.05), compared with SC and SPF. These pro-inflammatory cytokines
      concentrations were restored to control values (p < 0.05), when the animals were
      submitted to endurance training. CONCLUSION: Cancer-induced anorexia leads
      towards a pro-inflammatory state in the hypothalamus, which is prevented by
      endurance training which induces an anti-inflammatory state, with concomitant
      decrease of tumour weight.

PMID- 21861928
TI  - Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH
      oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells.
AB  - BACKGROUND: In the brain, the inducible form of heme oxygenase (HO-1) has been
      recently demonstrated to exacerbate early brain injury produced by intracerebral
      hemorrhagic stroke which incident rate has been correlated with cigarette smoking
      previously. Interestingly, cigarette smoke (CS) or chemicals present in CS have
      been shown to induce HO-1 expression in various cell types, including cerebral
      endothelial cells. However, the mechanisms underlying CS modulating HO-1 protein
      expression are not completely understood in the brain vessels. OBJECTIVE: The aim
      of the present study was to investigate the mechanisms underlying CS modulating
      HO-1 protein expression in cerebral endothelial cells. METHODS: Cultured cerebral
      endothelial cells (bEnd.3) were used to investigate whether a particulate phase
      of cigarette smoke extract (PPCSE) regulates HO-1 expression and to investigate
      the molecular mechanisms involved in HO-1 expression in bEnd.3 cells. RESULTS: We
      demonstrated that PPCSE (30 MUg/ml) significantly induced HO-1 protein expression
      and its enzymatic activity in bEnd.3 cells determined by western blotting and
      bilirubin formation, respectively. PPCSE-induced HO-1 expression was mediated
      through phosphatidylcholine phospholipase C (PC-PLC), PKCdelta, and PI3K/Akt
      which were observed by pretreatment with their respective pharmacological
      inhibitors or transfection with dominant negative mutants of PKCdelta and Akt.
      ROS scavenger (N-acetyl-L-cysteine, NAC) blocked the PPCSE-induced ROS generation
      and HO-1 expression. Pretreatment with selective inhibitors of PKCdelta
      (rottlerin) and NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin
      (APO)] attenuated the PPCSE-induced NADPH oxidase activity, ROS generation, and
      HO-1 expression. In addition, we found that PPCSE induced PI3K/Akt activation via
      NADPH oxidase/ROS-dependent PDGFR phosphorylation. CONCLUSIONS: Taken together,
      these results suggested that PPCSE-induced HO-1 expression is mediated by a PC
      PLC/PKCdelta/NADPH oxidase-dependent PDGFR/PI3K/Akt pathway in bEnd.3 cells.

PMID- 21861929
TI  - Transient myeloproliferative disorder in a newborn with down syndrome treated
      with rasburicase for the risk of development of tumor lysis syndrome: A case
      report.
AB  - INTRODUCTION: Transient myeloproliferative disorder is a hematologic abnormality
      characterized by an uncontrolled proliferation of myeloblasts in peripheral blood
      and bone marrow that primarily affects newborns and babies with Down syndrome.
      Tumor lysis syndrome is rarely associated with transient myeloproliferative
      disorder. CASE PRESENTATION: Transient myeloproliferative disorder was diagnosed
      in a seven-day-old baby girl with Down syndrome, who was referred to our
      department due to hyperleukocytosis. Our patient developed tumor lysis syndrome,
      successfully treated with rasburicase, as a complication of transient
      myeloproliferative disorder resulting from rapid degradation of myeloid blasts
      after initiation of effective chemotherapy. CONCLUSIONS: Tumor lysis syndrome is
      rarely reported as a complication of transient myeloproliferative disorder. To
      the best of our knowledge, this is the first case of a newborn with Down syndrome
      and transient myeloproliferative disorder treated with rasburicase for developing
      tumor lysis syndrome.

PMID- 21861930
TI  - A biofeedback cycling training to improve locomotion: a case series study based
      on gait pattern classification of 153 chronic stroke patients.
AB  - BACKGROUND: The restoration of walking ability is the main goal of post-stroke
      lower limb rehabilitation and different studies suggest that pedaling may have a
      positive effect on locomotion. The aim of this study was to explore the
      feasibility of a biofeedback pedaling treatment and its effects on cycling and
      walking ability in chronic stroke patients. A case series study was designed and
      participants were recruited based on a gait pattern classification of a
      population of 153 chronic stroke patients. METHODS: In order to optimize
      participants selection, a k-means cluster analysis was performed to subgroup
      homogenous gait patterns in terms of gait speed and symmetry.The training
      consisted of a 2-week treatment of 6 sessions. A visual biofeedback helped the
      subjects in maintaining a symmetrical contribution of the two legs during
      pedaling. Participants were assessed before, after training and at follow-up
      visits (one week after treatment). Outcome measures were the unbalance during a
      pedaling test, and the temporal, spatial, and symmetry parameters during gait
      analysis. RESULTS AND DISCUSSION: Three clusters, mainly differing in terms of
      gait speed, were identified and participants, representative of each cluster,
      were selected.An intra-subject statistical analysis (ANOVA) showed that all
      patients significantly decreased the pedaling unbalance after treatment and
      maintained significant improvements with respect to baseline at follow-up. The 2
      week treatment induced some modifications in the gait pattern of two patients:
      one, the most impaired, significantly improved mean velocity and increased gait
      symmetry; the other one reduced significantly the over-compensation of the
      healthy limb. No benefits were produced in the gait of the last subject who
      maintained her slow but almost symmetrical pattern. Thus, this study might
      suggest that the treatment can be beneficial for patients having a very
      asymmetrical and inefficient gait and for those that overuse the healthy leg.
      CONCLUSION: The results demonstrated that the treatment is feasible and it might
      be effective in translating progresses from pedaling to locomotion. If these
      results are confirmed on a larger and controlled scale, the intervention, thanks
      to its safety and low price, could have a significant impact as a home-
      rehabilitation treatment for chronic stroke patients.

PMID- 21861931
TI  - Tyrosine kinases in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an inflammatory, polyarticular joint disease. A
      number of cellular responses are involved in the pathogenesis of rheumatoid
      arthritis, including activation of inflammatory cells and cytokine expression.
      The cellular responses involved in each of these processes depends on the
      specific signaling pathways that are activated; many of which include protein
      tyrosine kinases. These pathways include the mitogen-activated protein kinase
      pathway, Janus kinases/signal transducers and activators transcription pathway,
      spleen tyrosine kinase signaling, and the nuclear factor kappa-light-chain
      enhancer of activated B cells pathway. Many drugs are in development to target
      tyrosine kinases for the treatment of RA. Based on the number of recently
      published studies, this manuscript reviews the role of tyrosine kinases in the
      pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic
      strategies of RA.

PMID- 21861933
TI  - Intracellular trafficking as a determinant of AS-DACA cytotoxicity in
      rhabdomyosarcoma cells.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma derived
      from skeletal muscle precursor cells, which accounts for 5-8% of all childhood
      malignancies. Disseminated RMS represents a major clinical obstacle, and the need
      for better treatment strategies for the clinically aggressive alveolar RMS
      subtype is particularly apparent. Previously, we have shown that the acridine-4
      carboxamide derivative AS-DACA, a known topoisomerase II poison, is potently
      cytotoxic in the alveolar RMS cell line RH30, but is 190-fold less active in the
      embryonal RMS cell line RD. Here, we investigate the basis for this selectivity,
      and demonstrate in these RMS lines, and in an AS-DACA- resistant subclone of
      RH30, that AS-DACA-induced cytotoxicity correlates with the induction of DNA
      double strand breaks. RESULTS: We show that inhibition of the multidrug
      resistance associated protein (MRP1) has no effect on AS-DACA sensitivity. By
      exploiting the pH-dependent fluorescence properties of AS-DACA, we have
      characterized its intracellular distribution, and show that it concentrates in
      the cell nucleus, as well as in acidic vesicles of the membrane trafficking
      system. We show that fluorescence microscopy can be used to determine the
      localization of AS-DACA to the nuclear and cytoplasmic compartments of RMS cells
      grown as spheroids, penetrance being much greater in RH30 than RD spheroids, and
      that the vesicular signal leads the way into the spheroid mass. EEA1 and Rab5
      proteins, molecular markers expressed on early-endosomal vesicles, are reduced by
      >50% in the sensitive cell lines. CONCLUSION: Taking the evidence as a whole,
      suggests that endosomal vesicle trafficking influences the toxicity of AS-DACA in
      RMS cells.

PMID- 21861932
TI  - Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional
      chemotherapy: a tangible union against chemoresistant cancer.
AB  - BACKGROUND: Late stage Ovarian Cancer is essentially incurable primarily due to
      late diagnosis and its inherent heterogeneity. Single agent treatments are
      inadequate and generally lead to severe side effects at therapeutic doses. It is
      crucial to develop clinically relevant novel combination regimens involving
      synergistic modalities that target a wider repertoire of cells and lead to
      lowered individual doses. Stemming from this premise, this is the first report of
      two- and three-way synergies between Adenovirus-mediated Purine Nucleoside
      Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel
      and/or carboplatin in multidrug-resistant ovarian cancer cells. METHODS: The
      effects of PNP-GDEPT on different cellular processes were determined using
      Shotgun Proteomics analyses. The in vitro cell growth inhibition in
      differentially treated drug resistant human ovarian cancer cell lines was
      established using a cell-viability assay. The extent of synergy, additivity, or
      antagonism between treatments was evaluated using CalcuSyn statistical analyses.
      The involvement of apoptosis and implicated proteins in effects of different
      treatments was established using flow cytometry based detection of M30 (an early
      marker of apoptosis), cell cycle analyses and finally western blot based
      analyses. RESULTS: Efficacy of the trimodal treatment was significantly greater
      than that achieved with bimodal- or individual treatments with potential for 10
      50 fold dose reduction compared to that required for individual treatments. Of
      note was the marked enhancement in apoptosis that specifically accompanied the
      combinations that included PNP-GDEPT and accordingly correlated with a shift in
      the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated
      enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic
      analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins
      involved in oncogenesis or cancer drug resistance in treated cells with
      accompanying upregulation of apoptotic- and tumour- suppressor proteins.
      CONCLUSION: Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to
      significant enhancement of the cancer cell susceptibility to the combined
      treatment. Overall, these data will underpin the development of regimens that can
      benefit patients with late stage ovarian cancer leading to significantly improved
      efficacy and increased quality of life.

PMID- 21861934
TI  - MLVA polymorphism of Salmonella enterica subspecies isolated from humans,
      animals, and food in Cambodia.
AB  - BACKGROUND: Salmonella (S.) enterica is the main cause of salmonellosis in humans
      and animals. The epidemiology of this infection involves large geographical
      distances, and strains related to an episode of salmonellosis therefore need to
      be reliably discriminated. Due to the limitations of serotyping, molecular
      genotyping methods have been developed, including multiple loci variable number
      of tandem repeats (VNTR) analysis (MLVA). In our study, 11 variable number tandem
      repeats markers were selected from the S. enterica Typhimurium LT2 genome to
      evaluate the genetic diversity of 206 S. enterica strains collected in Cambodia
      between 2001 and 2007. FINDINGS: Thirty one serovars were identified from three
      sources: humans, animals and food. The markers were able to discriminate all
      strains from 2 to 17 alleles. Using the genotype phylogeny repartition, MLVA
      distinguished 107 genotypes clustered into two main groups: S. enterica Typhi and
      other serovars. Four serovars (Derby, Schwarzengrund, Stanley, and Weltevreden)
      were dispersed in 2 to 5 phylogenic branches. Allelic variations within S.
      enterica serovars was represented using the minimum spanning tree. For several
      genotypes, we identified clonal complexes within the serovars. This finding
      supports the notion of endemo-epidemic diffusion within animals, food, or humans.
      Furthermore, a clonal transmission from one source to another was reported. Four
      markers (STTR3, STTR5, STTR8, and Sal20) presented a high diversity index (DI >
      0.80). CONCLUSIONS: In summary, MLVA can be used in the typing and genetic
      profiling of a large diversity of S. enterica serovars, as well as determining
      the epidemiological relationships of the strains with the geography of the area.

PMID- 21861935
TI  - Effects of Hylan G-F 20 supplementation on cartilage preservation detected by
      magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind
      clinical trial.
AB  - BACKGROUND: Although viscosupplementation is an effective symptomatic treatment
      for knee osteoarthritis (OA), the effect of longer term administration on
      articular cartilage has not been fully explored. We examined the effect of
      viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients
      with knee OA. METHODS: In this prospective, single-blind, parallel control group
      pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and
      III) were assigned to either intervention group (n = 39 receiving 4 courses of 3
      * 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or
      control group (n = 39 receiving usual care for knee OA without injections).
      Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24
      months. Cartilage volume and defects were assessed using validated methods.
      RESULTS: Fifty-five subjects (71%) completed 24 month follow up. Over 24 months,
      the intervention group had a reduced annual percentage rate of medial and lateral
      tibial cartilage volume loss (mean +/- SD, -0.3 +/- 2.7% and -1.4 +/- 4.3%)
      compared with the control group (2.3 +/- 2.6% and 1.4 +/- 2.6%, P = 0.001 and
      0.005 for difference, respectively). The intervention group also showed reduced
      cartilage defect score increment in the medial tibiofemoral compartment (0.1 +/-
      1.3) compared with the control group (0.8 +/- 1.5, P = 0.05). CONCLUSIONS: Six
      monthly intra-articular injections of Hylan G-F 20 administered to patients with
      symptomatic knee OA have a beneficial effect on knee cartilage preservation
      measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants
      further evaluation in larger clinical trials as a possible disease-modifying
      agent in the treatment of knee OA. TRIAL REGISTRATION: The study was registered
      with ClinicalTrials.gov (NCT00393393).

PMID- 21861936
TI  - The ACR11 encodes a novel type of chloroplastic ACT domain repeat protein that is
      coordinately expressed with GLN2 in Arabidopsis.
AB  - BACKGROUND: The ACT domain, named after bacterial aspartate kinase, chorismate
      mutase and TyrA (prephenate dehydrogenase), is a regulatory domain that serves as
      an amino acid-binding site in feedback-regulated amino acid metabolic enzymes. We
      have previously identified a novel type of ACT domain-containing protein family,
      the ACT domain repeat (ACR) protein family, in Arabidopsis. Members of the ACR
      family, ACR1 to ACR8, contain four copies of the ACT domain that extend
      throughout the entire polypeptide. Here, we describe the identification of four
      novel ACT domain-containing proteins, namely ACR9 to ACR12, in Arabidopsis. The
      ACR9 and ACR10 proteins contain three copies of the ACT domain, whereas the ACR11
      and ACR12 proteins have a putative transit peptide followed by two copies of the
      ACT domain. The functions of these plant ACR proteins are largely unknown.
      RESULTS: The ACR11 and ACR12 proteins are predicted to target to chloroplasts. We
      used protoplast transient expression assay to demonstrate that the Arabidopsis
      ACR11- and ACR12-green fluorescent fusion proteins are localized to the
      chloroplast. Analysis of an ACR11 promoter-beta-glucuronidase (GUS) fusion in
      transgenic Arabidopsis revealed that the GUS activity was mainly detected in
      mature leaves and sepals. Interestingly, coexpression analysis revealed that the
      GLN2, which encodes a chloroplastic glutamine synthetase, has the highest mutual
      rank in the coexpressed gene network connected to ACR11. We used RNA gel blot
      analysis to confirm that the expression pattern of ACR11 is similar to that of
      GLN2 in various organs from 6-week-old Arabidopsis. Moreover, the expression of
      ACR11 and GLN2 is highly co-regulated by sucrose and light/dark treatments in 2
      week-old Arabidopsis seedlings. CONCLUSIONS: This study reports the
      identification of four novel ACT domain repeat proteins, ACR9 to ACR12, in
      Arabidopsis. The ACR11 and ACR12 proteins are localized to the chloroplast, and
      the expression of ACR11 and GLN2 is highly coordinated. These results suggest
      that the ACR11 and GLN2 genes may belong to the same functional module. The
      Arabidopsis ACR11 protein may function as a regulatory protein that is related to
      glutamine metabolism or signaling in the chloroplast.

PMID- 21861937
TI  - A comparative gene expression database for invertebrates.
AB  - BACKGROUND: As whole genome and transcriptome sequencing gets cheaper and faster,
      a great number of 'exotic' animal models are emerging, rapidly adding valuable
      data to the ever-expanding Evo-Devo field. All these new organisms serve as a
      fantastic resource for the research community, but the sheer amount of data, some
      published, some not, makes detailed comparison of gene expression patterns very
      difficult to summarize - a problem sometimes even noticeable within a single lab.
      The need to merge existing data with new information in an organized manner that
      is publicly available to the research community is now more necessary than ever.
      DESCRIPTION: In order to offer a homogenous way of storing and handling gene
      expression patterns from a variety of organisms, we have developed the first web
      based comparative gene expression database for invertebrates that allows species
      specific as well as cross-species gene expression comparisons. The database can
      be queried by gene name, developmental stage and/or expression domains.
      CONCLUSIONS: This database provides a unique tool for the Evo-Devo research
      community that allows the retrieval, analysis and comparison of gene expression
      patterns within or among species. In addition, this database enables a quick
      identification of putative syn-expression groups that can be used to initiate,
      among other things, gene regulatory network (GRN) projects.

PMID- 21861938
TI  - The role of induced pluripotent stem cells in regenerative medicine:
      neurodegenerative diseases.
AB  - Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic
      lateral sclerosis, and Friedreich's ataxia are the most common human
      neurodegenerative diseases pathologically characterized by a progressive and
      specific loss of certain neuronal populations. The exact mechanisms of neuronal
      cell death in these diseases are unclear, although some forms of the diseases are
      inherited and genes causing these diseases have been identified. Currently there
      are no effective clinical therapies for many of these diseases. The recently
      acquired ability to reprogram human adult somatic cells to induced pluripotent
      stem cells (iPSCs) in culture may provide a powerful tool for in vitro
      neurodegenerative disease modeling and an unlimited source for cell replacement
      therapy. In the present review, we summarize recent progress on iPSC generation
      and differentiation into neuronal cell types and discuss the potential
      application for in vitro disease mechanism study and in vivo cell replacement
      therapy.

PMID- 21861940
TI  - Health benefits and health claims of probiotics: bridging science and marketing.
AB  - Health claims for probiotics are evaluated by the Panel on Dietetic Products,
      Nutrition and Allergies of the European Food Safety Authority. Despite a
      substantial amount of basic and clinical research on the beneficial effects of
      probiotics, all of the evaluated claim applications thus far have received a
      negative opinion. With the restrictions on the use of clinical endpoints,
      validated biomarkers for gut health and immune health in relation to reduction in
      disease risk are needed. Clear-cut criteria for design as well as evaluation of
      future studies are needed. An open dialogue between basic and clinical
      scientists, regulatory authorities, food and nutrition industry, and consumers
      could bridge the gap between science and marketing of probiotics.

PMID- 21861941
TI  - Glucose intolerance associated with early-life exposure to maternal cafeteria
      feeding is dependent upon post-weaning diet.
AB  - In addition to being a risk factor for adverse outcomes of pregnancy, maternal
      obesity may play a role in determining the long-term disease patterns observed in
      the resulting offspring, with metabolic and dietary factors directly programming
      fetal development. The present study evaluated the potential for feeding rats an
      obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation
      and for the offspring post-weaning, to programme glucose tolerance. Early-life
      exposure to an O diet had no significant effect on offspring food intake. Early
      life programming associated with O feeding to induce maternal obesity was
      associated with reduced adiposity in offspring weaned onto low-fat chow. Adult
      offspring exposed to an O diet in early life and weaned on a chow diet had low
      fasting glucose and insulin concentrations and appeared to be more sensitive to
      insulin during an intraperitoneal glucose tolerance test. When weaned on an O
      diet, male offspring were more prone to glucose intolerance than females. On the
      basis of the area under the glucose curve, maternal O feeding at any point from
      pre-mating to lactation was associated with impaired glucose tolerance. The
      mechanism for this was not identified, although increased hepatic expression of
      Akt2 may have indicated disturbance of insulin signalling pathways. The
      observations in the present study confirm that maternal overnutrition and obesity
      during pregnancy are risk factors for metabolic disturbance in the resulting
      offspring. Although the effects on glucose homeostasis were independent of
      offspring adiposity, the programming of a glucose-intolerant phenotype was only
      observed when offspring were weaned on a diet that induced greater fat
      deposition.

PMID- 21861942
TI  - The development and evaluation of a novel Internet-based computer program to
      assess previous-day dietary and physical activity behaviours in adults: the
      Synchronised Nutrition and Activity Program for Adults (SNAPATM).
AB  - The Synchronised Nutrition and Activity Program for Adults (SNAPATM) was
      developed to address the need for accurate, reliable, feasible, inexpensive and
      low-burden methods for assessing specific dietary and physical activity
      behaviours in adults. Short-term test-retest reliability of SNAPATM was assessed
      in forty-four adults (age 41.4 (SD17.3) years) who completed SNAPATM twice in 1
      day. Concurrent validity against direct dietary observation and combined heart
      rate and accelerometry was assessed in seventy-seven adults (age 34.4 (SD11.1)
      years). Test-retest reliability revealed no substantial systematic shifts in mean
      values of the outcome variables: percentage of food energy from fat (% fat),
      number of portions of fruit and vegetables (FV) and minutes of moderate-to
      vigorous physical activity (MVPA). For lunchtime dietary intake, the mean match
      rate between food items reported using SNAPATM and those observed was 81.7%, with
      a phantom rate of 5.6%. Pearson's correlations between SNAPATM and the reference
      methods ranged from 0.27 to 0.56 for % fat, FV portions and minutes of MVPA. For
      % fat and FV intake, there was no fixed or proportional bias, and mean
      differences between the methods (SNAPATM - reference) were 5.1% and 0 portions,
      respectively. For minutes of MVPA, a fixed bias of - 28 min was revealed when
      compared with all minutes of MVPA measured by combined heart rate and
      accelerometry, whereas a proportional bias (slope 1.47) was revealed when
      compared with minutes carried out in bouts >= 10 min. SNAPATM is a promising tool
      for measuring specific energy balance behaviours, though further work is required
      to improve accuracy for physical activity behaviours.

PMID- 21861939
TI  - Myofibroblast differentiation and survival in fibrotic disease.
AB  - During wound healing, contractile fibroblasts called myofibroblasts regulate the
      formation and contraction of granulation tissue; however, pathological and
      persistent myofibroblast activation, which occurs in hypertrophic scars or tissue
      fibrosis, results in a loss of function. Many reviews outline the cellular and
      molecular features of myofibroblasts and their roles in a variety of diseases.
      This review focuses on the origins of myofibroblasts and the factors that control
      their differentiation and prolonged survival in fibrotic tissues. Pulmonary
      fibrosis is used to illustrate many key points, but examples from other tissues
      and models are also included. Myofibroblasts originate mostly from tissue
      resident fibroblasts, and also from epithelial and endothelial cells or other
      mesenchymal precursors. Their differentiation is influenced by cytokines, growth
      factors, extracellular matrix composition and stiffness, and cell surface
      molecules such as proteoglycans and THY1, among other factors. Many of these
      effects are modulated by cell contraction. Myofibroblasts resist programmed cell
      death, which promotes their accumulation in fibrotic tissues. The cause of
      resistance to apoptosis in myofibroblasts is under ongoing investigation, but
      many of the same stimuli that regulate their differentiation are involved. The
      contributions of oxidative stress, the WNT-beta-catenin pathway and PPARgamma to
      myofibroblast differentiation and survival are increasingly appreciated.

PMID- 21861943
TI  - Folate malabsorption is associated with down-regulation of folate transporter
      expression and function at colon basolateral membrane in rats.
AB  - Folates, an essential component (important B vitamin) in the human diet, are
      involved in many metabolic pathways, mainly in carbon transfer reactions such as
      purine and pyrimidine biosynthesis and amino acid interconversions. Deficiency of
      this micronutrient leads to the disruption of folate-dependent metabolic pathways
      that lead to the development of clinical abnormalities ranging from anaemia to
      growth retardation. Folate deficiency due to alcohol ingestion is quite common,
      primarily due to malabsorption. The present study dealt with the mechanistic
      insights of folate malabsorption in colonic basolateral membrane (BLM). Wistar
      rats (n 12) were fed 1 g/kg body weight per d ethanol (20 %) solution orally for
      3 months and folate transport was studied in the isolated colonic BLM. The folate
      exit across colon BLM shows characteristics of carrier-mediated process with the
      major involvement of reduced folate carrier (RFC). The chronic ethanol ingestion
      decreased the uptake by decreasing the affinity by 46 % (P < 0.01) and the number
      of transport molecules by 43 % (P < 0.001) at the colon BLM. The decreased uptake
      was associated with down-regulation of proton-coupled folate transporter (PCFT)
      and RFC expression at mRNA and protein levels. The extent of decrease was 44 % (P
      < 0.01) and 24 % (P < 0.05) for PCFT and 23 % (P < 0.01) and 57 % (P < 0.01) for
      RFC at mRNA and protein levels, respectively. Moreover, folate transporters were
      associated with lipid rafts (LR) of colon BLM, and chronic alcoholism decreased
      the association of these transporters with LR.

PMID- 21861944
TI  - Sexuality in institutionalized elderly persons: a systematic review of argument
      based ethics literature.
AB  - BACKGROUND: Admission to a nursing home might challenge the way in which
      individuals experience their own sexuality, but it does not automatically
      diminish their need and desire for sexual fulfillment. Despite the fact that
      sexuality proves to be an intrinsic part of human existence, the sexual
      expression of geriatric residents remains a sensitive subject for many caregivers
      and family members. It evokes a variety of ethical issues and concerns,
      especially when dementia patients are involved. The overall objective of this
      review was to examine the ethical arguments and concepts about the debate on
      sexuality within a nursing home environment. METHODS: We conducted a systematic
      search for argument-based ethics literature focusing on sexuality in
      institutionalized elderly people. Twenty-five appropriate studies were
      identified. RESULTS: A thematic analysis of the included literature led us to
      distinguish two major groups of ethical arguments: (i) principles and (ii) care.
      Ethics arguments on sexuality in institutionalized elderly are particularly
      guided by the principle of respect for autonomy and the concomitant notion of
      informed consent. Arguments related to care were also apparent within the
      research literature although they received considerably less attention than the
      arguments related to the principles of respect for autonomy, beneficence,
      nonmaleficence and justice. CONCLUSIONS: The lack of clarity in the
      conceptualization of the arguments referred to in the research literature
      indicates that there is a pressing need for a better defined, more fundamental
      philosophical-ethical analysis of the values at stake.

PMID- 21861945
TI  - Closing the praziquantel treatment gap: new steps in epidemiological monitoring
      and control of schistosomiasis in African infants and preschool-aged children.
AB  - Where very young children come into contact with water containing schistosome
      cercariae, infections occur and schistosomiasis can be found. In high
      transmission environments, where mothers daily bathe their children with
      environmentally drawn water, many infants and preschool-aged children have
      schistosomiasis. This 'new' burden, inclusive of co-infections with Schistosoma
      haematobium and Schistosoma mansoni, is being formally explored as infected
      children are not presently targeted to receive praziquantel (PZQ) within current
      preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists
      whereby infected children might wait up to 4-5 years before receiving first
      treatment in school. International treatment guidelines, set within national
      treatment platforms, are presently being modified to provide earlier access to
      medication(s). Although detailed pharmacokinetic studies are needed, to
      facilitate pragmatic dosing in the field, an extended 'dose pole' has been
      devised and epidemiological monitoring has shown that administration of PZQ (40
      mg/kg), in either crushed tablet or liquid suspension, is both safe and effective
      in this younger age-class; drug efficacy, however, against S. mansoni appears to
      diminish after repeated rounds of treatment. Thus use of PZQ should be combined
      with appropriate health education/water hygiene improvements for both child and
      mother to bring forth a more enduring solution.

PMID- 21861947
TI  - An evaluation of vitamin D status in individuals with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where
      genetic susceptibility coupled with largely undefined environmental factors is
      reported to underlie the aetiology of the disease. One such factor is low vitamin
      D status. The primary source of vitamin D is endogenous synthesis following
      exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the
      use of sun protection factor in combination with medications prescribed to treat
      the symptoms of the disease, puts SLE patients at increased risk of vitamin D
      deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically
      active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment
      common in SLE putting additional stress on vitamin D metabolism. The majority of
      studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using
      varying cut-offs (<25 to <80 nmol/l). Of these studies, fifteen have investigated
      a link between status and disease activity with conflicting results. Variation
      with disease activity index measures used alongside methodological limitations
      within the study design may partially explain these findings. This review
      discusses the importance of optimal vitamin D status in SLE, critically evaluates
      research carried out to date that has investigated vitamin D in SLE, and
      highlights the need for a well-designed observational study that controls for
      diet, medication use, dietary supplements, UV exposure and seasonality, that uses
      sensitive methods for measuring vitamin D status and disease activity in SLE to
      conclusively establish the role of vitamin D in SLE.

PMID- 21861946
TI  - Detection of Dicrocoelium dendriticum larval stages in mollusc and ant
      intermediate hosts by PCR, using mitochondrial and ribosomal internal transcribed
      spacer (ITS-2) sequences.
AB  - The aim of this study was to develop, perfect and validate the PCR (polymerase
      chain reaction) technique using mitochondrial (mt) and ribosomal (ITS-2) DNA for
      the accurate identification of Dicrocoelium dendriticum in molluscs and ants, the
      first and second intermediate hosts, and their early detection. The first primers
      that were designed amplified a 169 pb mtDNA fragment of D. dendriticum permitted
      the detection of a single D. dendriticum metacercaria from the Formica rufibarbis
      and Formica pratensis abdomen, as well as the detection of the brainworm in the
      head of the ants collected in tetania. Although these primers did not amplify
      Dicrocoelium chinensis DNA and permitted detected D. dendriticum in the molluscs,
      they did not discriminate Brachylaimidae metacercariae found in the same mollusc.
      The PCR that was designed to amplify a 93 bp fragment of the ITS-2 is D.
      dendriticum specific as it did not amplify D. chinensis, Brachylaimidae and other
      trematodes. This technique is very sensitive since it permitted the detection of
      D. dendriticum in the molluscs from the first day post-infection, the brainworm
      in the head of the ants and only 1 D. dendriticum metacercaria from the abdomen
      of the ants. Both techniques are important, mainly the latter.

PMID- 21861948
TI  - How does infant behaviour relate to weight gain and adiposity?
AB  - An understanding of how infant eating behaviour relates to later obesity is
      required if interventions in infancy are to be attempted. The aim of this paper
      is to review findings from the Gateshead Millennium Study to describe (i) what we
      have already established about the relationship between infant feeding
      transitions, infancy weight gain and eating behaviour and (ii) describe new
      analyses that examine how infant eating behaviour and temperament relate to
      infancy weight gain and childhood adiposity. The Gateshead Millennium Study
      recruited 1029 infants at birth and parents completed questionnaires five times
      in the first year. We have already described how starting solids and ceasing
      breast-feeding seems to be a response to rapid early weight gain, rather than a
      cause, and that parents identify and respond to the individual appetite
      characteristics of their child. A number of questions about eating behaviour at
      12 months were used to construct an infancy eating avidity score that was
      positively associated with height at age 7-8 years, but not with an adiposity
      index constructed using bioelectrical impedance, waist and skinfolds. Infancy
      eating avidity score was associated with greater fussiness and lower satiety
      responsivity on the Child Eating Behaviour Questionnaire at age 6-8 years.
      Temperament measured at age 6 weeks and 8 months showed no consistent
      associations with either infancy weight gain or adiposity at 6-8 years. While
      infancy may seem a logical time to intervene with children at risk of future
      obesity, the collective findings from this substantial population-based study
      largely suggest otherwise.

PMID- 21861949
TI  - Does vitamin D during pregnancy impact offspring growth and bone?
AB  - During pregnancy, maternal and fetal Ca demands are met through increased
      intestinal Ca absorption. Increased Ca absorption may be more dependent on
      oestrogen's up-regulation of Ca transport genes than on vitamin D status.
      Numerous studies, however, have found that severe vitamin D deficiency with
      secondary hyperparathyroidism during pregnancy leads to abnormal Ca homoeostasis
      in the neonate. Some, but not all, studies of maternal vitamin D supplementation
      during pregnancy find a greater birth weight among infants of mothers with
      adequate vitamin D status. Observational studies find a higher incidence of small
      for-gestational age (SGA) infants among mothers who are vitamin D deficient, but
      this effect may be modified by genetics. In addition, the effect of vitamin D
      status on SGA may not be linear, with increased occurrence of SGA at high
      maternal 25-hydroxyvitamin D (25-OHD) concentrations. Some studies, but not all,
      also have found that maternal vitamin D status is associated with growth
      trajectory during the first year of life, although the findings are
      contradictory. There are recent studies that suggest maternal 25-OHD, or
      surrogates of vitamin D status, are associated with growth and bone mass later in
      childhood. These results are not consistent, and blinded randomised trials of
      vitamin D supplementation during pregnancy with long-term follow-up are needed to
      determine the benefits, and possible risks, of maternal vitamin D status on
      offspring growth and bone development. The possibility of adverse outcomes with
      higher maternal 25-OHD concentrations should be considered and investigated in
      all ongoing and future studies.

PMID- 21861950
TI  - Endothelial dysfunction associated with obesity and the effect of weight loss
      interventions.
AB  - Endothelial damage is central to the initiation and progression of
      atherosclerosis, while in addition vascular endothelial cells secrete several
      anti-atherogenic substances including the potent vasodilator nitric oxide.
      Increased adhesion molecule expression, in response to pathophysiological stimuli
      is perhaps the earliest indicator of compromised endothelial integrity. Obesity
      and adiposity are associated with an increased risk of CVD, influencing disease
      progression via a number of mechanisms, including enhanced endothelial
      activation. This review discusses possible mechanisms linking adiposity and more
      specifically regional fat depots with endothelial function and evaluates studies
      investigating the effect of weight loss on endothelial function, assessed by
      biochemical and physiological measurements. Overall, the research to date
      suggests that visceral adiposity is a stronger predictor of endothelial
      activation than overall adiposity, possibly mediated via the action of NEFA in
      circulation. While in general there is a suggestion that weight loss is
      associated with significant improvements in endothelial function, this is not
      apparent in all interventions and published literature to date provides less than
      convincing evidence for the effects of weight loss on endothelial activation.

PMID- 21861951
TI  - Simultaneous evaluation of the harms and benefits of treatments in randomized
      clinical trials: demonstration of a new approach.
AB  - BACKGROUND: One aim of personalized medicine is to determine which treatment is
      to be preferred for an individual patient, given all patient information
      available. Particularly in mental health, however, there is a lack of a single
      objective, reliable measure of outcome that is sensitive to crucial individual
      differences among patients. METHOD: We examined the feasibility of quantifying
      the total clinical value provided by a treatment (measured by both harms and
      benefits) in a single metric. An expert panel was asked to compare 100 pairs of
      patients, one from each treatment group, who had participated in a randomized
      clinical trial (RCT) involving interpersonal psychotherapy (IPT) and
      escitalopram, selecting the patient with the preferred outcome considering both
      benefits and harms. RESULTS: From these results, an integrated preference score
      (IPS) was derived, such that the differences between any two patients' IPSs would
      predict the clinicians' preferences. This IPS was then computed for all patients
      in the RCT. A second set of 100 pairs was rated by the panel. Their preferences
      were highly correlated with the IPS differences (r=0.84). Finally, the IPS was
      used as the outcome measure comparing IPT and escitalopram. The 95% confidence
      interval (CI) for the effect size comparing treatments indicated clinical
      equivalence of the treatments. CONCLUSIONS: A metric that combines benefits and
      harms of treatments could increase the value of RCTs by making clearer which
      treatments are preferable and, ultimately, for whom. Such methods result in more
      precise estimation of effect sizes, without increasing the required sample size.

PMID- 21861952
TI  - Concordance between personality disorder assessment methods.
AB  - BACKGROUND: Studies have criticized the low level of agreement between the
      various methods of personality disorder (PD) assessment. This is an important
      issue for research and clinical purposes. METHOD: Seven hundred and forty-two
      participants in the Hopkins Epidemiology of Personality Disorders Study (HEPS)
      were assessed on two occasions using the Personality Disorder Schedule (PDS) and
      the International Personality Disorder Examination (IPDE). The concordance
      between the two diagnostic methods for all DSM-IV PDs was assessed using standard
      methods and also two item response analytic approaches designed to take account
      of measurement error: a latent trait-based approach and a generalized estimating
      equations (GEE)-based approach, with post-hoc adjustment. RESULTS: Raw criteria
      counts, using the intraclass correlation coefficient (ICC), kappa and odds ratio
      (OR), showed poor concordance. The more refined statistical methods showed a
      moderate to moderately high level of concordance between the methods for most PDs
      studied. Overall, the PDS produced lower prevalences of traits but higher
      precision of measurement than the IPDE. Specific criteria within each PD showed
      varying endorsement thresholds and precision for ascertaining the disorder.
      CONCLUSIONS: Concordance in the raw measurement of the individual PD criteria
      between the two clinical methods is lacking. However, based on two statistical
      methods that adjust for differential endorsement thresholds and measurement error
      in the assessments, we deduce that the PD constructs themselves can be measured
      with a moderate degree of confidence regardless of the clinical approach used.
      This may suggest that the individual criteria for each PD are, in and of
      themselves, less specific for diagnosis, but as a group the criteria for each PD
      usefully identify specific PD constructs.

PMID- 21861953
TI  - Deficient emotional self-regulation and pediatric attention deficit hyperactivity
      disorder: a family risk analysis.
AB  - BACKGROUND: Although deficient emotional self-regulation (DESR) is associated
      with attention deficit hyperactivity disorder (ADHD), little research
      investigates this association and little is known about its etiology. Family
      studies provide a method of clarifying the co-occurrence of clinical features,
      but no family studies have yet addressed ADHD and DESR in children. METHOD:
      Subjects were 242 children with ADHD and 224 children without ADHD. DESR was
      operationalized using an aggregate score >=180 and <210 in the anxious/depressed,
      attention and aggression scales (AAA profile) of the Child Behavior Checklist
      (CBCL), termed the CBCL-DESR profile. The CBCL-bipolar (CBCL-BP) profile was
      defined as >=210 on the CBCL-AAA scale. We examined the familial transmission of
      ADHD and the CBCL-AAA scale in families selected through probands with and
      without these conditions. RESULTS: We found a linear increase in the prevalence
      of CBCL-DESR in siblings as indexed by the Control, ADHD, ADHD+CBCL-DESR and
      ADHD+CBCL-BP proband groups. While the ADHD siblings were at elevated risk for
      both the CBCL-DESR and CBCL-BP compared with non-ADHD siblings, a significantly
      higher rate of CBCL-BP in the siblings of ADHD+CBCL-BP probands was found
      compared with siblings of the Control probands. CONCLUSIONS: ADHD shows the same
      degree of familial transmission in the presence or absence of DESR. CBCL-DESR and
      CBCL-BP are familial, but further work is needed to determine if these
      definitions are distinctly familial or represent a continuum of the same
      psychopathology.

PMID- 21861954
TI  - Auditory hallucinations in childhood: associations with adversity and delusional
      ideation.
AB  - BACKGROUND: Previous work suggests that exposure to childhood adversity is
      associated with the combination of delusions and hallucinations. In the present
      study, associations between (severity of) auditory vocal hallucinations (AVH) and
      (i) social adversity [traumatic experiences (TE) and stressful events (SE)] and
      (ii) delusional ideation were examined. METHOD: A baseline case-control sample of
      children with and without AVH were re-assessed on AVH after 5 years and
      interviewed about the experience of social adversity and delusions. RESULTS: A
      total of 337 children (mean age 13.1 years, S.D.=0.5) were assessed: 40 children
      continued to hear voices that were present at baseline (24%, persistent group),
      15 heard voices only at follow-up (9%, incident group), 130 children no longer
      reported AVH that were present at baseline (remitted group) and 152 never heard
      voices (referent group). Both TE and SE were associated with both incident and
      persistent AVH, as well as with greater AVH severity and delusional ideation at
      follow-up. In addition, the combination of AVH and delusions displayed a stronger
      association with TE and SE compared with either AVH or delusions alone.
      CONCLUSIONS: Early childhood AVH are mostly benign and transitory. However,
      experience of social adversity is associated with persistence, severity and onset
      of new AVH closer to puberty, and with delusional ideation.

PMID- 21861956
TI  - [Topical rapamycin solution to treat multiple facial angiofibromas in a patient
      with tuberous sclerosis].

PMID- 21861955
TI  - Terbium, a fluorescent probe for investigation of siderophore pyochelin
      interactions with its outer membrane transporter FptA.
AB  - Pyochelin (Pch) is a siderophore and FptA is its outer membrane transporter
      produced by Pseudomonas aeruginosa to import iron. The fluorescence of the
      element terbium is affected by coordinated ligands and it can therefore be used
      as a probe to investigate the pyochelin-iron uptake pathway in P. aeruginosa. At
      pH 8.0, terbium fluorescence is greatly enhanced in the presence of pyochelin
      indicating chelation of the metal by the siderophore. Titration curves showed a
      2:1 (Pch:Tb(3+)) stoichiometry and an affinity of K=(2+/--1)*10(11)M(-2) was
      determined. Pch-Tb interaction with the transporter FptA could be followed in
      vitro and in vivo in P. aeruginosa cells, by Fluorescence Resonance Energy
      Transfer (FRET) between three partners: the tryptophans of FptA (donor), Pch
      (acceptor for the Trps and donor for Tb(3+)) and Tb(3+) (acceptor). Pch-Tb binds
      to the Pch-Fe outer membrane transporter FptA with a dissociation constant (K(d))
      of 4.6MUM. This three-partner FRET is a potentially valuable tool for
      investigation of the interactions between FptA and its siderophore Pch.

PMID- 21861957
TI  - Polyelectrolyte-macroion coacervation. Foreword.

PMID- 21861958
TI  - The cardiac malpositions.
AB  - Dextrocardia was known in the 17th century and was 1 of the first congenital
      malformations of the heart to be recognized. Fifty years elapsed before Matthew
      Baillie published his account of complete transposition in a human of the
      thoracic and abdominal viscera to the opposite side from what is natural. In
      1858, Thomas Peacock stated that "the heart may be congenitally misplaced in
      various ways, occupying either an unusual position within the thorax, or being
      situated external to that cavity." In 1915, Maude Abbott described ectopia
      cordis, and Richard Paltauf's remarkable illustrations distinguished the various
      types of dextrocardia. In 1928, the first useful classification of the cardiac
      malpositions was proposed, and in 1966, Elliott et al's radiologic classification
      set the stage for clinical recognition. The first section of this review deals
      with the 3 basic cardiac malpositions in the presence of bilateral asymmetry. The
      second section deals with cardiac malpositions in the presence of bilateral left
      sidedness or right-sidedness. Previous publications on cardiac malpositions are
      replete with an arcane vocabulary that confounds rather than clarifies. Even if
      the terms themselves are understood, inherent complexity weighs against clarity.
      This review was designed as a guided tour of an unfamiliar subject.

PMID- 21861959
TI  - Stent-related cardiac events beyond three years after implantation of the
      sirolimus-eluting stent (from the EVASTENT Patients).
AB  - The frequency of very late stent thrombosis (VLST) up to 3 years after sirolimus
      eluting stent implantation is 0.5% to 0.6%/year but incertitude remains about the
      frequency of VLAST after 3 years. Diabetic (db+) and nondiabetic (db-) patients
      with or without multiple diseased vessels included in the EVASTENT matched-cohort
      registry were followed up to 6 years after stent implantation. Long-term follow
      up was obtained for 1,564 of the 1,731 included patients. All-cause deaths
      (including cancer and complications of diabetes) occurred at steady rates of
      2.5%/year up to 3 years and 1.2%/year after 3 years (difference not significant).
      In contrast, VLST (any Academic Research Consortium definition) was only
      0.18%/year (95% confidence interval 0.08 to 0.39) after 3 years versus 0.63%/year
      (confidence interval 0.41 to 0.98) from 1 year to 3 years (p = 0.03). Target
      lesion revascularization rates were also lower after 3 years than before 3 years
      (1.9% vs 7%, p <= 0.01) with 66% of revascularization procedures after 3 years
      being for nontarget lesions. Six-year all-cause death and cardiac death
      cumulative rates were higher in db+ than in db- patients. However, after 3 years
      compared to before 3 years, no differences between db+ and db- patients were
      observed for target lesion revascularization and ST rates. It is noteworthy that
      51% of patients continued to be on clopidogrel therapy nearly 6 years after
      receiving >= 1 sirolimus-eluting stent. In conclusion, all-cause deaths continued
      at a steady rate over 6 years. However, cardiac deaths and "very" VLST leveled
      out beyond 3 years.

PMID- 21861960
TI  - Prediction of hemodynamic severity of coarctation by magnetic resonance imaging.
AB  - A published formula containing minimal aortic cross-sectional area and the flow
      deceleration pattern in the descending aorta obtained by cardiovascular magnetic
      resonance predicts significant coarctation of the aorta (CoA). However, the
      existing formula is complicated to use in clinical practice and has not been
      externally validated. Consequently, its clinical utility has been limited. The
      aim of this study was to derive a simple and clinically practical algorithm to
      predict severe CoA from data obtained by cardiovascular magnetic resonance.
      Seventy-nine consecutive patients who underwent cardiovascular magnetic resonance
      and cardiac catheterization for the evaluation of native or recurrent CoA at
      Children's Hospital Boston (n = 30) and the University of California, San
      Francisco (n = 49), were retrospectively reviewed. The published formula derived
      from data obtained at Children's Hospital Boston was first validated from data
      obtained at the University of California, San Francisco. Next, pooled data from
      the 2 institutions were analyzed, and a refined model was created using logistic
      regression methods. Finally, recursive partitioning was used to develop a
      clinically practical prediction tree to predict transcatheter systolic pressure
      gradient >= 20 mm Hg. Severe CoA was present in 48 patients (61%). Indexed
      minimal aortic cross-sectional area and heart rate-corrected flow deceleration
      time in the descending aorta were independent predictors of CoA gradient >= 20 mm
      Hg (p <0.01 for both). A prediction tree combining these variables reached a
      sensitivity and specificity of 90% and 76%, respectively. In conclusion, the
      presented prediction tree on the basis of cutoff values is easy to use and may
      help guide the management of patients investigated for CoA.

PMID- 21861961
TI  - Efficacy of the RADPAD protective drape during real world complex percutaneous
      coronary intervention procedures.
AB  - The RADPAD is a lead-free surgical drape containing bismuth and barium that has
      been demonstrated to reduce scatter radiation exposure to primary operators
      during fluoroscopic procedures. It is not known to what degree the RADPAD reduces
      radiation exposure in operators who perform highly complex percutaneous coronary
      intervention (PCI) requiring prolonged fluoroscopic screening times. Sixty
      consecutive patients due to undergo elective complex PCI involving rotational
      atherectomy, multivessel PCI, or chronic total occlusions were randomized in a
      1:1 pattern to have their procedures performed with and without the RADPAD drape
      in situ. Dosimetry was performed on the left arm of the primary operator. There
      were 40 cases of chronic total occlusion, including 28 with contralateral
      injections; 15 cases involving rotational atherectomy; and 5 cases of multivessel
      PCI. There was no significant difference in screening times or dose-area products
      between the 2 patient groups. Primary operator radiation dose relative to
      screening time (RADPAD: slope = 1.44, R2 = 0.25; no RADPAD: slope = 4.60, R2 =
      0.26; analysis of covariance F = 4.81, p = 0.032) and dose-area product (RADPAD:
      slope = 0.003, R2 = 0.26; no RADPAD: slope = 0.011, R2 = 0.52; analysis of
      covariance F = 12.54, p = 0.008) was significantly smaller in the RADPAD cohort
      compared to the no-RADPAD group. In conclusion, the RADPAD significantly reduces
      radiation exposure to primary operators during prolonged, complex PCI cases.

PMID- 21861962
TI  - Natural history and outcome of mucinous carcinoma of the ovary.
AB  - OBJECTIVE: We performed a population-based analysis to compare the clinical
      characteristics of women with mucinous tumors with women with other epithelial
      tumors. STUDY DESIGN: The Surveillance, Epidemiology, and End Results database
      was queried to identify all women with epithelial ovarian cancer diagnosed from
      1988 to 2007. The natural history, clinical characteristics, and survival of
      women with serous tumors were compared with women with mucinous carcinomas.
      RESULTS: A total of 40,571 women including 4811 with mucinous carcinomas (11.9%)
      were identified. Among women with stage I neoplasms, the presence of mucinous
      histology had no effect on either cancer-specific survival (hazard ratio, 0.87;
      95% confidence interval, 0.74-1.04). Survival was inferior in patients with
      advanced-stage mucinous compared with serous tumors. The hazard ratio for cancer
      specific survival for women with stage III mucinous tumors was 1.55 (95%
      confidence interval, 1.43-1.96). CONCLUSION: Although survival for early-stage
      mucinous and serous tumors is similar, survival for advanced-stage mucinous
      neoplasms is inferior to that of serous carcinomas.

PMID- 21861963
TI  - Arteriovenous malformation following conservative treatment of placenta percreta
      with uterine artery embolization but no adjunctive therapy.

PMID- 21861964
TI  - Adverse events following administration to pregnant women of influenza A (H1N1)
      2009 monovalent vaccine reported to the Vaccine Adverse Event Reporting System.
AB  - OBJECTIVE: The objective of the study was to evaluate and summarize reports to
      the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting
      system, in pregnant women who received influenza A (H1N1) 2009 monovalent vaccine
      to assess for potential vaccine safety problems. STUDY DESIGN: We reviewed
      reports of adverse events (AEs) in pregnant women who received 2009-H1N1 vaccines
      from Oct. 1, 2009, through Feb. 28, 2010. RESULTS: VAERS received 294 reports of
      AEs in pregnant women who received 2009-H1N1 vaccine: 288 after inactivated and 6
      after the live attenuated vaccines. Two maternal deaths were reported. Fifty-nine
      women (20.1%) were hospitalized. We verified 131 pregnancy-specific outcomes: 95
      spontaneous abortions (<20 weeks); 18 stillbirths (>=20 weeks); 7 preterm
      deliveries (<37 weeks); 3 threatened abortions; 2 preterm labor; 2 preeclampsia;
      and 1 each of fetal hydronephrosis, fetal tachycardia, intrauterine growth
      retardation, and cleft lip. CONCLUSION: Review of reports to VAERS following H1N1
      vaccination in pregnant women did not identify any concerning patterns of
      maternal or fetal outcomes.

PMID- 21861965
TI  - Shoulder dystocia training effects.

PMID- 21861967
TI  - Quantitative analysis of renal vascularization in fetuses with urinary tract
      obstruction by three-dimensional power-Doppler.
AB  - OBJECTIVE: To evaluate the applicability of 3-dimensional evaluation of renal
      vascularization for predicting postnatal renal function in fetuses with suspected
      urinary obstruction. STUDY DESIGN: Fetuses were evaluated by 3-dimensional power
      Doppler histogram, and vascular indices were estimated. Depth between the probe
      and the renal cortex was also evaluated. Postnatal follow-up was obtained in all
      cases and the main outcome was renal impairment. RESULTS: Twenty-three fetuses
      with urinary dilatation (cases) and 73 with normal renal morphology (controls)
      were included in the current study. Five (21.7%) cases developed renal
      impairment. Vascularization index and vascularization and flow index were
      significantly lower in fetuses that developed renal impairment compared with
      those with normal renal function (P = .009 and P = .036, respectively). The 3
      vascular indexes correlated with depth. Percentage of depth-corrected
      vascularization index and vascularization flow index were lower in fetuses
      developing postnatal renal failure. CONCLUSION: Fetal renal vascularity
      (vascularization index and vascularization and flow index) was significantly
      lower in fetuses that developed renal impairment.

PMID- 21861968
TI  - Lactate detection in the brain of growth-restricted fetuses with magnetic
      resonance spectroscopy.
AB  - OBJECTIVE: The objective of the study was to determine the feasibility of
      detecting fetal brain lactate, a marker of fetal metabolic acidemia, using a
      noninvasive technique, proton magnetic resonance spectroscopy ((1)H MRS), in
      intrauterine growth-restricted (IUGR) fetuses. STUDY DESIGN: In vivo human fetal
      brain lactate detection was determined by (1)H MRS in 5 fetuses with IUGR.
      Oxygenation and acid-base balance data were obtained at birth. RESULTS: (1)H MRS
      analysis showed the presence of a lactate peak in the brain of the most severely
      affected IUGR fetus, with abnormal umbilical artery Doppler and fetal heart rate
      tracing. This finding was consistent with the low oxygen content and high lactic
      acid concentration observed in umbilical blood obtained at delivery. CONCLUSION:
      (1)H MRS allows the noninvasive detection of cerebral lactate in IUGR fetuses.
      Lactate detected by (1)H MRS may represent a possible marker of in utero cerebral
      injury or underperfusion.

PMID- 21861969
TI  - Brain metabolism in fetal intrauterine growth restriction: a proton magnetic
      resonance spectroscopy study.
AB  - OBJECTIVE: The purpose of this study was to investigate alterations in brain
      metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of
      cerebral redistribution of blood flow. STUDY DESIGN: Biometry and Doppler
      assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and
      cerebral redistribution and in 41 appropriately grown control subjects. Proton
      magnetic resonance spectroscopy of the fetal brain was then performed to
      determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA),
      and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr. RESULTS:
      Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and
      creatine peaks were identified in all these spectra; lactate was present in 5
      IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were
      significantly lower in IUGR fetuses with cerebral redistribution. CONCLUSION:
      Cerebral redistribution is associated with altered brain metabolism that is
      evidenced by a reduction in NAA:Cho and NAA:Cr ratios.

PMID- 21861970
TI  - Nonaneurysmal cranial nerve compression as cause of neuropathic strabismus:
      evidence from high-resolution magnetic resonance imaging.
AB  - PURPOSE: To seek evidence of neurovascular compression of motor cranial nerves
      (CNs) in otherwise idiopathic neuropathic strabismus using high-resolution
      magnetic resonance imaging (MRI). DESIGN: Prospective, observational case series.
      METHODS: High-resolution, surface coil orbital MRI was performed in 10 strabismic
      patients with idiopathic oculomotor (CN III) or abducens (CN VI) palsy.
      Relationships between CNs and intracranial arteries were demonstrated by 0.8-mm
      thick, 162-MUm resolution, heavily T2-weighted MRI in fast imaging using steady
      state acquisition sequences. Images were analyzed digitally to evaluate cross
      sectional areas of extraocular muscles. RESULTS: In one patient with CN III
      palsy, an ectatic posterior communicating artery markedly flattened and thinned
      the ipsilateral subarachnoid CN III. Cross-sections of the affected medial,
      superior, and inferior rectus muscles 10 mm posterior to the globe-optic nerve
      junction were 17.2 +/- 2.5 mm(2), 15.5 +/- 1.3 mm(2), and 9.9 +/- 0.8 mm(2),
      significantly smaller than the values of 23.6 +/- 1.9 mm(2), 30.4 +/- 4.1 mm(2),
      and 28.8 +/- 4.6 mm(2), respectively, of the unaffected side (P < .001). In 2
      patients with otherwise unexplained CN VI palsy, ectatic basilar arteries
      contacted CN VI. Mean cross-sections of affected lateral rectus muscles were 24.0
      +/- 2.3 mm(2) and 29.8 +/- 3.1 mm(2), significantly smaller than the values of
      33.5 +/- 4.1 mm(2) and 36.9 +/- 1.6 mm(2), respectively, in unaffected
      contralateral eyes (P < .05). CONCLUSIONS: Nonaneurysmal motor CN compression
      should be considered as a cause of CN III and CN VI paresis with neurogenic
      muscle atrophy when MRI demonstrates vascular distortion of the involved CN.
      Demonstration of a benign vascular cause can terminate continuing diagnostic
      investigations and can expedite rational management of the strabismus.

PMID- 21861971
TI  - Identifying a clinically meaningful threshold for change in uveitic macular edema
      evaluated by optical coherence tomography.
AB  - PURPOSE: To identify a clinically meaningful threshold for change in retinal
      thickness measured by optical coherence tomography for patients with uveitic
      macular edema using correlation with change in visual acuity. DESIGN: Cross
      sectional and longitudinal study. METHODS: One hundred twenty-eight eyes (101
      individuals) with macular edema enrolled in the Multicenter Uveitis Steroid
      Treatment (MUST) trial. At enrollment and after 6 months of follow-up, retinal
      thickness was measured at the central subfield with time-domain optical coherence
      tomography and visual acuity was measured with logarithmic (Early Treatment
      Diabetic Retinopathy Study) visual acuity charts. Participants were classified as
      having macular edema if the retinal thickness was 260 MUm or more. RESULTS: A
      threshold for change in retinal center subfield thickness of 20% balanced the
      percentage of false positives and false negatives for predicting more than a 10
      letter change in visual acuity with a sensitivity of 77% and a specificity of
      75%. The results were similar for more than 5-letter changes and for 15-letter or
      more changes. Those with a 20% or more reduction in retinal thickness had a mean
      11.0-letter improvement (95% confidence interval, 7.7 to 14.3) as compared with a
      -0.4-letter change (95% confidence interval, -4.1 to 3.3) in visual acuity for
      those without a 20% reduction (P < .01). CONCLUSIONS: In addition to being above
      the level of measurement uncertainty, a 20% change in retinal thickness in
      patients with macular edema seems to be optimal for clinically important changes
      in visual acuity and may be considered as an outcome for clinical trials of
      treatments for uveitic macular edema.

PMID- 21861972
TI  - Prophylactic selective laser trabeculoplasty in the prevention of intraocular
      pressure elevation after intravitreal triamcinolone acetonide injection.
AB  - PURPOSE: To evaluate the prophylactic efficacy of selective laser trabeculoplasty
      for preventing an increase in intraocular pressure (IOP) after intravitreal
      triamcinolone acetonide injection. DESIGN: Prospective, comparative,
      interventional case series. METHODS: We studied 31 eyes with a baseline IOP of 21
      mm Hg or more of 31 patients for which intravitreal triamcinolone acetonide
      injection was planned for diabetic macular edema. The patients were divided into
      2 groups, a study group and control group. The study group comprised 15 eyes of
      15 patients that underwent selective laser trabeculoplasty a mean of 8.3 +/- 4.1
      days before intravitreal triamcinolone acetonide injection. The control group
      comprised 16 eyes of 16 patients who underwent only intravitreal triamcinolone
      acetonide injection. Main outcomes measures were mean IOP and number of patients
      requiring antiglaucomatous therapy. RESULTS: Mean baseline IOP was 21.6 +/- 0.9
      mm Hg in the study group and 21.5 +/- 0.8 mm Hg in the control group (P = .98).
      Mean IOP at 1 day after injection was 17.0 +/- 2.0 mm Hg in the study group and
      19.5 +/- 4.3 mm Hg in the control group (P = .23). Mean IOP at 1 week after
      injection was 16.9 +/- 1.7 mm Hg and 18.4 +/- 4.0 mm Hg, respectively (P = .49);
      mean IOP at 1 month after injection was 16.4 +/- 1.5 mm Hg and 20.8 +/- 5.6 mm
      Hg, respectively (P = .003); mean IOP at 3 months after injection was 15.8 +/-
      2.5 mm Hg and 18.3 +/- 5.5 mm Hg, respectively (P = .01); and mean IOP at 6
      months after injection was 15.7 +/- 1.4 mm Hg and 17.1 +/- 1.5 mm Hg,
      respectively (P = .03). The number of patients requiring antiglaucomatous therapy
      during follow-up was 0 of 15 eyes in the study group and 8 of 16 eyes in the
      control group (P = .001). CONCLUSIONS: The IOP elevation after intravitreal
      triamcinolone acetonide injection may be prevented by performing selective laser
      trabeculoplasty before intravitreal triamcinolone acetonide injection, especially
      in cases with a baseline IOP of 21 mm Hg or more.

PMID- 21861973
TI  - Antimicrobial resistance profiles of ocular and nasal flora in patients
      undergoing intravitreal injections.
AB  - PURPOSE: To identify the resistance profiles of conjunctival and nasal bacterial
      isolates in patients undergoing intravitreal injections and to determine if
      frequent exposures to topical fluoroquinolones increased antimicrobial resistance
      among these organisms. DESIGN: Prospective cohort study. METHODS: Patients
      undergoing intravitreal injection at our institution were enrolled in this study.
      The conjunctiva and nares of both sides of the patient's face were swabbed and
      cultured before antiseptic preparation for intravitreal injection. At the time of
      the study, all patients received 3 days of moxifloxacin eye drops after each
      intravitreal injection as prophylaxis against endophthalmitis. Resistance to
      antimicrobials was analyzed using the chi-square test and t test. RESULTS: Two
      hundred eight conjunctival and nasal specimens were cultured from 104 patients.
      Forty-two (45%) of 93 patients had at least 1 fluoroquinolone-resistant organism
      in the nose or conjunctiva. Twelve (48%) of 25 patients with no previous
      injections had at least 1 resistant organism; 14 (45%) of 31 patients with 1 to 4
      previous injections had at least 1 resistant organism; 8 (33%) of 24 patients
      with 5 to 9 previous injections had at least 1 resistant organism; and 8 (62%) of
      13 patients with 10 or more previous injections had at least 1 resistant organism
      (P = .88; chi-square test, linear by linear association). CONCLUSIONS: In this
      small study, there was no correlation between the number of exposures to topical
      fluoroquinolones and resistance to fluoroquinolones in nasal and conjunctival
      flora, but there was a high prevalence of fluoroquinolone resistance among all
      patient groups.

PMID- 21861974
TI  - Evaluation of posterior lens capsule by 20-MHz ultrasound probe in traumatic
      cataract.
AB  - PURPOSE: To investigate the accuracy of echography with a 20-MHz probe for
      evaluation of posterior lens capsule in traumatic cataract before surgery.
      DESIGN: Prospective interventional case series. METHODS: This study consisted of
      43 eyes with traumatic cataract that were scheduled to undergo surgery. In all
      cases, cataract was dense enough to prevent visualization of the posterior lens
      capsule. Echography was performed using a 20-MHz probe to detect rupture of the
      posterior lens capsule. All patients subsequently underwent cataract extraction
      and intraoperative findings of the posterior lens capsule were compared with the
      preoperative echographic findings. RESULTS: This study included 43 eyes of 43
      patients (38 men and 5 women) with a mean age of 35.6 +/- 15.3 years (range, 4-68
      years). The trauma was either blunt (4 eyes) or sharp (39 eyes); there was closed
      globe injury in 2 eyes and open globe injury in 41 eyes. By 20-MHz echography,
      posterior border of the crsytalline lens was clearly visualized in all 43 eyes.
      By 20-MHz echographic imaging, rupture of the posterior lens capsule was
      identified in 17 eyes (39.5%). During cataract surgery, it was noted that 14 eyes
      (32.6%) had rupture of the posterior lens capsule. Sensitivity, specificity,
      positive predictive value, and negative predictive value were 93%, 86%, 76%, and
      96%, respectively, for 20-MHz echography to detect rupture of the posterior lens
      capsule. Also, the positive likelihood ratio, negative likelihood ratio, and odds
      ratio were 6.7, 0.08, and 81, respectively. CONCLUSION: Echography with 20-MHz
      probe is an accurate imaging modality for detection of posterior lens capsule
      rupture in traumatic cataract preoperatively. This technique helps
      ophthalmologists have an appropriate surgical plan before operating.

PMID- 21861975
TI  - Aqueous humor levels of vascular endothelial growth factor before and after
      intravitreal bevacizumab in type 3 versus type 1 and 2 neovascularization. A
      prospective, case-control study.
AB  - PURPOSE: To determine the aqueous levels of vascular endothelial growth factor
      (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related
      macular degeneration (AMD) and to compare the levels of those with type 1 and 2
      NV secondary to AMD before and after administration of intravitreal bevacizumab
      (IVB). DESIGN: Prospective, case-control study. METHODS: Aqueous samples were
      collected from 29 eyes of 29 patients with untreated wet AMD at baseline (day of
      the first IVB), month 1 (day of the second IVB), and month 2 (day of the third
      IVB). Among them, 10 eyes presented with type 1, 9 with type 2, and 10 with type
      3 NV. A group of 14 aqueous samples from 14 patients who underwent cataract
      surgery without other ocular or systemic disease comprised the controls. Main
      outcome measures were concentration of VEGF at baseline and after IVB in the 3 NV
      groups; secondary outcome measures included best-corrected visual acuity (BCVA)
      and central macular thickness (CMT) changes after IVB. Levels of VEGF were
      determined by commercially available enzyme-linked immunosorbent assay kits.
      RESULTS: VEGF concentrations in aqueous humor at baseline were higher in patients
      with type 3 NV when compared to controls (P = .0001) and type 1 and 2 NV patients
      (P = .002 and P = .0001 respectively). At month 1, levels of VEGF were
      significantly reduced compared to baseline (P < .05) and significantly lower
      compared to the controls (P < .005) in each NV group. These low levels were
      maintained at the 2-month interval. BCVA significantly improved in type 1 and 2
      NV groups (P < .05). CMT significantly reduced in each NV group compared to
      baseline (P < .05). CONCLUSION: In eyes with untreated wet AMD, aqueous levels of
      VEGF are significantly higher in type 3 NV than in type 1 or 2 NV. Regardless of
      the type of NV, aqueous VEGF levels significantly reduce 1 month after IVB as
      compared to both the baseline measurements and the values recorded in age-matched
      controls. These decreases are maintained at 2 months after administering a second
      IVB 30 days after the initial injection.

PMID- 21861976
TI  - Corneal collagen cross-linking with riboflavin and ultraviolet-A irradiation in
      patients with thin corneas.
AB  - PURPOSE: To report the outcomes after corneal collagen cross-linking (CXL)
      treatment with riboflavin and ultraviolet-A (UVA) irradiation in patients with
      thin corneas (minimum corneal thickness less than 400 MUm after epithelial
      removal and before riboflavin instillation). DESIGN: Prospective case series.
      METHODS: Twelve patients (14 eyes, with minimum corneal thickness less than 400
      MUm after epithelial removal) were included in the study. All patients underwent
      riboflavin-UVA-induced CXL using the standard CXL (Dresden) protocol. Uncorrected
      distance visual acuity (UDVA) and corrected distance visual acuity (CDVA)
      (decimal scale), manifest refraction (diopters, D), and topography were evaluated
      at baseline and at 1, 3, 6, and 12 months follow-up. Images of the endothelium
      were acquired with a modified confocal scanning laser ophthalmoscope. RESULTS: No
      intraoperative or postoperative complications were observed in this patient
      series. Mean minimum preoperative corneal thickness at the apex of the cone after
      epithelial removal and before riboflavin instillation was 373.92 +/- 22.92 MUm
      (range 340-399 MUm). UDVA and CDVA improved from 0.25 +/- 0.15 and 0.40 +/- 0.20
      to 0.27 +/- 0.17 and 0.49 +/- 0.20 respectively at the last follow-up
      examination. There was a reduction of the mean keratometry readings from 51.99 +/
      5.57 D to 49.33 +/- 4.82 D at the last follow-up. A significant decrease of
      endothelial cell density was observed (preoperative: 2733 +/- 180 cells/mm(2)
      [range 2467-3016], last follow-up visit: 2441 +/- 400 cells/mm(2) [range 1448
      2920], P < .01). CONCLUSIONS: CXL in thin corneas with minimum corneal thickness
      less than 400 MUm after epithelial removal seems to result in a significant
      endothelial cell density decrease postoperatively. This finding was not related
      to other intraoperative or postoperative complications.

PMID- 21861977
TI  - Accuracy and reliability of telemedicine for diagnosis of cytomegalovirus
      retinitis.
AB  - PURPOSE: To determine the feasibility of remote diagnostic screening for
      cytomegalovirus (CMV) retinitis among HIV patients in northern Thailand. DESIGN:
      Prospective, observational cross-sectional study. METHODS: One hundred eighty-two
      eyes from 94 consecutive patients with HIV seen in 2008 and 2009 at a tertiary
      university-based medical center were photographed using a digital retinal camera.
      Individual and composite images were uploaded to a secure web site. Three expert
      graders accessed the electronic images and graded each image for signs of CMV
      retinitis. Results of remote expert grading were compared with on-site patient
      examination by local expert ophthalmologists. RESULTS: On-site ophthalmologists
      diagnosed CMV retinitis in 89 (48.9%) of 182 eyes. Trained ophthalmic
      photographers obtained digital retinal images for all 182 eyes. As compared with
      the on-site examinations, the sensitivity for detecting CMV retinitis by remote
      readers using composite retinal images ranged from 89% to 91%. The specificity
      for detecting CMV retinitis by remote readers ranged from 85% to 88%. Intrarater
      reliability was high, with each grader achieving a kappa value of 0.93.
      Interrater reliability among the 3 graders also was high, with a kappa value of
      0.86. CONCLUSIONS: Remote diagnostic screening for CMV retinitis among HIV
      positive patients may prove to be a valuable tool in countries where the burden
      of HIV exceeds the capacity of the local eye care providers to screen for ocular
      opportunistic infections.

PMID- 21861978
TI  - Impact of three-dimensional analysis of multidetector row computed tomography
      cholangioportography in operative planning for hilar cholangiocarcinoma.
AB  - BACKGROUND: A detailed evaluation of portal triad structures, especially the
      biliary anatomy at the hepatic hilus, is essential to ensure curative resection
      for hilar cholangiocarcinoma. METHODS: Patients underwent 3-dimensional analysis
      using multidetector row computed tomography cholangioportography preoperatively.
      The number of bile duct orifices in the cut end of the hilar plate was estimated
      and compared with the actual number of bile ducts. Furthermore, the estimated
      length of the surgical margin and its relationship to the pathological margin
      status was evaluated. RESULTS: The number of bile duct orifices was correctly
      estimated in 14 of 19 patients. Of 18 hepatic ducts in which the estimated length
      of the hepatic side surgical margin was calculated 17 hepatic ducts (94.4%) were
      diagnosed pathologically as margin negative. CONCLUSIONS: This investigatory
      technique has the advantages of precise visualization of anatomic structures and
      multidirectional assessment of biliary branches and vessels, allowing improved
      operative planning for the treatment of hilar cholangiocarcinoma.

PMID- 21861979
TI  - Laparoscopic right hepatectomy: a challenging, but feasible, safe and efficient
      procedure.
AB  - BACKGROUND: Few centers are undertaking major laparoscopic liver resections,
      because of the well-recognized technical difficulties and lack of training
      opportunities. METHODS: The authors describe their technique for laparoscopic
      right hepatectomy, highlighting relevant details for accomplishing a safe and
      efficient procedure. Patients were chronologically divided into 2 groups to
      evaluate the impact of increasing experience on the surgical outcomes. RESULTS:
      Group I included 17 patients and group II 18 patients. The conversion rate to
      open or hybrid techniques significantly decreased from 36% in group I to 6% in
      group II (P = .03). The hospital stay decreased from a median of 6 days in group
      I to a median of 4 days in group II (P = .05). Complications occurred in 4
      patients (11%), of whom 3 were in group I. The mortality was zero. CONCLUSIONS:
      Laparoscopic right hepatectomy is a safe and efficient procedure when performed
      at specialized centers with extensive experience in hepatic surgery. Long-term
      training is necessary to acquire adequate expertise.

PMID- 21861980
TI  - Assessment of communication, professionalism, and surgical skills in an objective
      structured performance-related examination (OSPRE): a psychometric study.
AB  - BACKGROUND: The purpose of this study was to investigate the reliability and
      validity of a performance assessment of communication, professionalism, and
      surgical skills competencies for surgery residents. METHODS: Fourteen residents
      from the general surgery program of the University of Calgary were assessed in 7
      surgical simulation stations that included communication and professionalism
      skills. RESULTS: The internal consistency reliability of the checklists and
      global rating scales combined was adequate for communication (alpha = .75-.92)
      and surgical skills (alpha = .86-.96), but not for professionalism (alpha = 0).
      There was evidence of validity as surgical skills performance improved as a
      function of postgraduate year level but not for the professionalism checklist.
      Surgical skills and communication correlated in the 2 stations assessed (r = .55
      and .57; P < .05). CONCLUSIONS: There is evidence for both reliability and
      validity for simultaneously assessing surgical skills and communication skills.
      Further instrument development is required to assess professionalism in a
      structured examination context.

PMID- 21861981
TI  - Dyspnea and large bowel obstruction: a misleading Chilaiditi syndrome.
AB  - Chilaiditi sign is named after the Greek radiologist Demetrius Chilaiditi who
      first described it when he was working in Vienna In (1910), and it is an
      incidental radiographic finding. This sign can be more frequently mistaken for
      pneumoperitoneum which is usually an indication of bowel perforation and can lead
      to needless surgical intervention. There are several case report reported in
      literature that describe the association between colonic volvulus and Chilaiditi
      syndrome that underline the frequent association between these anatomical
      condition instead no previous report described the association between Chilaiditi
      syndrome and large bowel obstruction secondary to a malignant sigmoid stenosis in
      a man presenting with symptoms and signs of upper respiratory distress combined
      with subacute bowel obstruction.

PMID- 21861982
TI  - Incidence and prognosis of parathyroid gland carcinoma: a population-based study
      in The Netherlands estimating the preoperative diagnosis.
AB  - BACKGROUND: Parathyroid carcinoma is a rare malignancy and generally is diagnosed
      after surgery for primary hyperparathyroidism. Lack of a preoperative diagnosis
      and ill-considered surgical planning with its impact on survival are ill
      described. METHODS: In a retrospective population-based cohort study the clinical
      features, treatment, recurrences, and survival of 41 parathyroid cancer patients
      are reported and compared with characteristics of patients with primary
      hyperparathyroidism. RESULTS: Patients with parathyroid carcinoma had
      significantly higher serum parathyroid hormone and calcium levels compared with
      patients with primary hyperparathyroidism. Nineteen patients (46%) had a palpable
      neck mass. A parathyroid hormone level more than 3 times the upper normal limits
      was suspicious and levels more than 10 times carried a positive predictive value
      of 84% for carcinoma. Ten-year recurrence-free and disease-specific survival
      rates were 71% and 79%, respectively. CONCLUSIONS: Parathyroid hormone levels of
      more than 3 times upper normal limits, palpable neck mass, and profound
      hypercalcemia are suspicious signs of carcinoma necessitating surgical
      exploration by an experienced surgeon.

PMID- 21861984
TI  - Involvement of HMGB1 and RAGE in IL-1beta-induced gingival inflammation.
AB  - OBJECTIVE: Extracellularly released high mobility group box 1 (HMGB1) protein
      behaves as a cytokine, promotes inflammation and participates in the pathogenesis
      of several disorders in peripheral organs. The role of HMGB1 and receptor for
      advanced glycation end products (RAGE) expressed in gingival inflammatory tissues
      was explored. METHODS: Real time PCR was applied to assay HMGB1 and RAGE mRNA
      expression in gingival epithelial and fibroblast cells induced by interleukin
      1beta (IL-1beta). A highly selective inhibitor of inducible nitric oxide (iNOS)
      was employed. ELISA was done for measurement of HMGB1 concentrations in cell
      culture media of gingival epithelial and fibroblast cells. Immunohistochemistry
      was performed to analyse the expression and sub-cellular localization of HMGB1,
      together with RAGE, in specimens obtained from patients with chronic
      inflammation. RESULTS: A time-dependent response of HMGB1 and RAGE expression in
      gingival cells to IL-1beta induction was observed. IL-1beta promotes HMGB1
      production in human gingival epithelial cells in a nitric oxide-dependent manner.
      HMGB1 and RAGE appeared highly expressed in gingival inflammatory tissues.
      CONCLUSION: These results demonstrate that HMGB1 and RAGE are abundantly
      expressed in gingiva and promptly released during gingival inflammation. We
      suggest a role for HMGB1/RAGE/iNOS signalling on inflamed gingival epithelial
      cells.

PMID- 21861985
TI  - Evidence of an early physical activity reduction in chronic obstructive pulmonary
      disease patients.
AB  - OBJECTIVE: To compare the lifetime pattern of physical activity (PA) in chronic
      obstructive pulmonary disease (COPD) patients and sedentary healthy subjects
      (SHS) using a PA questionnaire with a lifetime period of recall (Quantification
      de l'Activite Physique [QUANTAP] system), and to compare the pattern of PA
      reduction in COPD patients with the onset of breathlessness and other relevant
      clinical events in this disease (diagnosis, first rehabilitation, onset of
      smoking). DESIGN: Cross-sectional comparative study. SETTINGS: Outpatient
      university hospital and inpatient pulmonary rehabilitation center. PARTICIPANTS:
      COPD patients (n=129; mean age +/- SD, 61+/-10y; forced expiratory volume in 1s,
      57+/-23%) and SHS (n=29; mean age +/- SD, 61+/-5y; <150min.wk(-1) of moderate
      vigorous PA). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lifetime PA
      was compared in COPD patients and SHS using the QUANTAP system. The patients with
      COPD and SHS underwent pulmonary function, exercise, and quadriceps endurance
      testing. The current PA level was assessed with a triaxial accelerometer and the
      Voorrips questionnaire. The age at the onset of breathlessness was also recorded.
      RESULTS: Accelerometry showed no significant difference between patients and SHS
      (in vector magnitude units, 136+/-56 vs 135+/-47; P=.95). Within the past 15
      years, the cumulated PA level was not different for each 5-year period. Then,
      from the period of 16 to 40 years ago, it was systematically higher in patients
      compared with SHS (in metabolic equivalent/y(-1); median [interquartile range],
      6973 [5400-12,207] vs 4248 [3545-5919]; P<.05). The COPD patients reduced their
      PA earlier than the SHS (45y vs 55y; P<.01), and the PA was dropped before the
      onset of breathlessness (45y vs 49y; P<.001). CONCLUSIONS: The observation of an
      early PA reduction, preceding the onset of breathlessness, suggests the
      implication of prior pathologic mechanisms in the PA reduction of COPD patients.

PMID- 21861986
TI  - Negative and nonemotional interference with visual working memory in
      schizophrenia.
AB  - BACKGROUND: Schizophrenia (SCZ) results in abnormalities affecting both working
      memory (WM) and emotional processing. Prior work suggests that individuals with
      SCZ exhibit increased effects of distraction on WM-a deficit that might be
      exacerbated via emotional interference. However, no study characterized effects
      of negative and nonemotional interference on visual WM in SCZ with functional
      magnetic resonance imaging. We tested the hypothesis that SCZ is associated with
      a general inability to filter distraction versus a specific deficit in the
      ability to filter aversive emotional distraction. METHODS: Twenty-eight patients
      with DSM-IV-diagnosed SCZ and 24 matched control subjects underwent blood-oxygen
      level-dependent imaging with functional magnetic resonance imaging at 3-T.
      Subjects performed a modified delayed-response visual WM task faced with
      affectively negative, neutral, or task-related interference. RESULTS: Control
      subjects showed maximal interference after aversive distraction, whereas patients
      were more distracted irrespective of interference type. Importantly, aversive
      distraction resulted in similar across-group activation in regions previously
      showing robust effects of negative interference. Conversely, after any
      distraction, patients showed reduced blood-oxygen-level-dependent activity in
      prefrontal regions previously implicated in filtering interference. Particularly
      when distracted, SCZ subjects exhibited aberrant responses to nonemotional
      distraction across posterior cortical regions. CONCLUSIONS: Results suggest that
      patients fail to deploy activity associated with distracter filtering exhibited
      by control subjects. Although SCZ subjects show similar responses to aversive
      interference across certain regions, there is also evidence of enhanced responses
      to nonemotional inputs. These results are consistent with a general deficit in
      the ability of patients to filter distraction, which might be in line with
      aberrant salience processing as a pathophysiological mechanism in SCZ.

PMID- 21861987
TI  - Mefloquine blockade of connexin 36 and connexin 43 gap junctions and risk of
      suicide.

PMID- 21861989
TI  - New triterpenoid saponins from the roots of Gypsophila perfoliata Linn.
AB  - Nine new triterpenoid saponins (1-9) have been isolated from the roots of
      Gypsophila perfoliata Linn. Their structures were established on the basis of
      extensive NMR ((1)H, (13)C, HSQC and HMBC) and ESIMS studies.

PMID- 21861990
TI  - Structure and genetics of the O-antigen of Escherichia coli O158.
AB  - A structure of the O-polysaccharide (O-antigen) of Escherichia coli O158 has been
      reported (Datta, A. K.; Basu, S.; Roy, N. Carbohydr. Res.1999, 322, 219-227). In
      this work, we reinvestigated the O158 polysaccharide using sugar analyses, Smith
      degradation, and (1)H and (13)C NMR spectroscopy and established the following
      structure, which is at variance with the structure established earlier: [see
      formula in text]. This structure is in agreement with the predicted functions of
      genes found in the O-antigen gene cluster of E. coli O158.

PMID- 21861988
TI  - Clinical symptoms and alpha band resting-state functional connectivity imaging in
      patients with schizophrenia: implications for novel approaches to treatment.
AB  - BACKGROUND: Schizophrenia (SZ) is associated with functional decoupling between
      cortical regions, but we do not know whether and where this occurs in low
      frequency electromagnetic oscillations. The goal of this study was to use
      magnetoencephalography (MEG) to identify brain regions that exhibit abnormal
      resting-state connectivity in the alpha frequency range in patients with
      schizophrenia and investigate associations between functional connectivity and
      clinical symptoms in stable outpatient participants. METHODS: Thirty patients
      with SZ and 15 healthy comparison participants were scanned in resting-state MEG
      (eyes closed). Functional connectivity MEG source data were reconstructed
      globally in the alpha range, quantified by the mean imaginary coherence between a
      voxel and the rest of the brain. RESULTS: In patients, decreased connectivity was
      observed in left prefrontal cortex (PFC) and right superior temporal cortex,
      whereas increased connectivity was observed in left extrastriate cortex and the
      right inferior PFC. Functional connectivity of left inferior parietal cortex was
      negatively related to positive symptoms. Low left PFC connectivity was associated
      with negative symptoms. Functional connectivity of midline PFC was negatively
      correlated with depressed symptoms. Functional connectivity of right PFC was
      associated with other (cognitive) symptoms. CONCLUSIONS: This study demonstrates
      direct functional disconnection in SZ between specific cortical fields within low
      frequency resting-state oscillations. Impaired alpha coupling in frontal,
      parietal, and temporal regions is associated with clinical symptoms in these
      stable outpatients. Our findings indicate that this level of functional
      disconnection between cortical regions is an important treatment target in SZ.

PMID- 21861991
TI  - Triterpenoid saponins with antifeedant activities from stem bark of Catunaregam
      spinosa (Rubiaceae) against Plutella xylostella (Plutellidae).
AB  - Seven triterpenoid saponins, including four new compounds, catunarosides A-D (1
      4), and three known compounds, swartziatrioside (5), aralia-saponin V (6),
      araliasaponin IV (7) were isolated from the stem bark of Catunaregam spinosa, a
      Chinese mangrove associate. Their structures were elucidated on the basis of
      their spectral data and hydrolysis experiments. The antifeedant activities of
      compounds 1-7 against Plutella xylostella were also evaluated.

PMID- 21861992
TI  - Characterization of peripheral blood acetylcholine receptor-binding B cells in
      experimental myasthenia gravis.
AB  - In myasthenia gravis (MG), the neuromuscular transmission is impaired by
      antibodies (Abs) specific for muscle acetylcholine receptor (AChR). Anti-AChR Abs
      can be detected in the serum of MG patients, although their levels do not
      correlate with disease severity. In this study, we developed a flow cytometric
      assay for the detection of peripheral blood AChR-specific B cells to characterize
      B cell phenotypes associated with experimental autoimmune myasthenia gravis
      (EAMG). Alexa-conjugated AChR was used as a probe for AChR-specific B cells
      (B220+Ig+). Mice with EAMG had significantly elevated frequencies of AChR
      specific IgG2+ and IgM+ B cells. While the frequencies of IgG2+ B cells and
      plasma anti-AChR IgG2 levels significantly correlated with the clinical grades of
      EAMG, the frequencies of IgM+ B cells and plasma anti-AChR IgM levels did not.
      These results indicate that the frequency of AChR-specific and IgG1+ (mouse IgG2
      equivalent) peripheral blood B cells and anti-AChR IgG1 levels could be potential
      biomarkers for MG disease severity.

PMID- 21861993
TI  - [Giant retroperitoneal abscess after duodenal perforation during duodenal
      endoscopy].

PMID- 21861994
TI  - Methods for isolation of cell-free plasma DNA strongly affect DNA yield.
AB  - Extracellular nucleic acids are present in plasma, serum, and other body fluids
      and their analysis has gained increasing attention during recent years. Because
      of the small quantity and highly fragmented nature of cell-free DNA in plasma and
      serum, a fast, efficient, and reliable isolation method is still a problem and so
      far there is no agreement on a standardized method. We used spin columns from
      commercial suppliers (QIAamp DNA Blood Midi Kit from Qiagen; NucleoSpin Kit from
      Macherey-Nagel; MagNA Pure isolation system from Roche Diagnostics) to isolate
      DNA from 44 plasma samples in parallel at laboratories in Berlin and Munich. DNA
      in all samples was quantified by real-time PCR on a LightCycler 480 using three
      different targets (GAPDH, beta-globin, ERV). The quantities of cell-free DNA for
      the different isolation methods and genes varied between medians of 1.6 ng/mL and
      28.1 ng/mL. This considerable variation of absolute DNA values was mainly caused
      by the use of different isolation methods (p<0.0001). Comparable results were
      achieved by the use of the genes GAPDH and ERV while higher values were obtained
      by use of beta-globin. The laboratory site had only minor influence on DNA yield
      when manual extraction methods were used.

PMID- 21861995
TI  - Radiation dose of non-enhanced chest CT can be reduced 40% by using iterative
      reconstruction in image space.
AB  - AIM: To evaluate the image quality and dose reduction capability of non-enhanced
      chest computed tomography (CT) examinations using iterative reconstruction in
      image space (IRIS). MATERIALS AND METHODS: A CT water phantom was scanned at 120
      kV/150 mAs and 100 kV/270 mAs as the reference, and the tube current was
      decreased in 10% intervals down to 40% of the reference value. Image noise was
      evaluated and compared between filtered back-projection (FBP) and IRIS
      reconstructed data. In the patient study, 90 patients underwent non-enhanced
      chest CT examinations; the patients were randomly assigned into three groups:
      group A (n=30) standard dose protocol, 120 kV/110 mAs; group B (n=30) low dose,
      100 kV/110 mAs; group C (n=30) low dose, 120 kV/67 mAs. All images were
      reconstructed by FBP and IRIS algorithm using matched kernels of B30 and I30. The
      objective image noise (OIN), signal-to-noise ratio (SNR), and contrast-to-noise
      ratio (CNR) of the aorta and latissimus dorsi were measured. The subjective image
      quality and noise were scored using a three-point scale by two experienced
      radiologists. The results of the subjective and objective image assessment were
      compared between groups B and C (low dose) IRIS and group A (standard dose) FBP.
      RESULTS: The phantom study showed comparable image noise between the scans using
      60% dose with IRIS and 100% dose with FBP for both 120 and 100 kV. In the patient
      study, groups A, B, and C had effective dose of 3.81 +/- 0.43, 2.40 +/- 0.19, and
      2.41 +/- 0.15 mSv. IRIS significantly improved the OIN, SNR, and CNR compared
      with FBP for the same patient. The OIN, SNR, and CNR using IRIS in group B and C
      were improved or comparable to those in group A using FBP. No significant
      difference was found in subjective image quality and noise between groups B and C
      using IRIS and group A using FBP. CONCLUSION: Compared with FBP, IRIS can
      maintain or improve image quality on unenhanced chest CT image reconstruction
      while saving 40% radiation dose.

PMID- 21861996
TI  - Tc99m-hepatobiliary iminodiacetic acid (HIDA) scintigraphy in clinical practice.
AB  - There have been evolutionary changes in the management of pathological conditions
      of the hepatobiliary system over recent years, particularly with an increasing
      emphasis on modern hepatobiliary surgical techniques. Concurrent advances have
      occurred in imaging technology and availability, leading to a greater use of
      ultrasound, multidetector computed tomography (CT), and magnetic resonance
      imaging (MRI) in the primary evaluation of hepatobiliary disease. Radionuclide
      imaging using technetium(99m) (Tc(99m)) hepatobiliary iminodiacetic acid (HIDA)
      derivatives is an established technique that complements morphological imaging,
      providing valuable functional information in both pre- and postoperative
      evaluation of patients with suspected or known hepatobiliary disease. This review
      discusses the current clinical indications for Tc(99m) HIDA scintigraphy using
      clinical cases to demonstrate how this technique continues to play a valuable
      diagnostic role in the assessment of the functional integrity of the
      hepatobiliary system.

PMID- 21861997
TI  - When help becomes hindrance: unexpected errors of omission and commission in
      eyewitness memory resulting from change temporal order at retrieval?
AB  - An experimental mock eyewitness study is reported that compared Free and reverse
      order recall of an empirically informed scripted crime event. Proponents of
      reverse order recall suggest it facilitates recovery of script incidental
      information and increases the total amount of information recalled. However,
      compared with free recall it was found to impair overall retrieval performance,
      resulting in fewer script consistent events, reduced recall of correct
      information, increased confabulations, and lowered accuracy proportional to items
      retrieved. The disruptive effects of reverse order are interpreted as providing
      evidence for the role of temporal clustering in guiding retrieval. Impairment
      induced by reverse order continued to influence retrieval negatively even during
      a secondary free recall phase suggesting it encourages confabulations. The
      results indicate that the technique should be used with caution, and only when
      retrieval by free recall has been exhausted.

PMID- 21861998
TI  - Do 10-month-old infants understand others' false beliefs?
AB  - As adults, we know that others' mental states, such as beliefs, guide their
      behavior and that these mental states can deviate from reality. Researchers have
      examined whether young children possess adult-like theory of mind by focusing on
      their understanding about others' false beliefs. The present research revealed
      that 10-month-old infants seemed to interpret a person's choice of toys based on
      her true or false beliefs about which toys were present. These results indicate
      that like adults, even preverbal infants act as if they can consider others'
      mental states when making inferences about others' actions.

PMID- 21861999
TI  - Challenge and error: critical events and attention-related errors.
AB  - Attention lapses resulting from reactivity to task challenges and their
      consequences constitute a pervasive factor affecting everyday performance errors
      and accidents. A bidirectional model of attention lapses (error<->attention
      lapse: Cheyne, Solman, Carriere, & Smilek, 2009) argues that errors beget errors
      by generating attention lapses; resource-depleting cognitions interfering with
      attention to subsequent task challenges. Attention lapses lead to errors, and
      errors themselves are a potent consequence often leading to further attention
      lapses potentially initiating a spiral into more serious errors. We investigated
      this challenge-induced error<->attention-lapse model using the Sustained
      Attention to Response Task (SART), a GO-NOGO task requiring continuous attention
      and response to a number series and withholding of responses to a rare NOGO
      digit. We found response speed and increased commission errors following task
      challenges to be a function of temporal distance from, and prior performance on,
      previous NOGO trials. We conclude by comparing and contrasting the present theory
      and findings to those based on choice paradigms and argue that the present
      findings have implications for the generality of conflict monitoring and control
      models.

PMID- 21862000
TI  - Following the Aznalcollar toxic spill.
AB  - Ten years after the Aznalcollar mine spill, the decline in metal contamination in
      the area is evident. However, some elements are still found in elevated
      concentrations. In Scrobicularia plana, zinc, lead, and arsenic exceeded health
      advisory levels at several locations although there is no indication of risks
      associated with consumption of this mollusc. The estuary seems to have enhanced
      the bioavailability of arsenic and lead. Research should continue to understand
      the significance of this contamination.

PMID- 21862001
TI  - Increase of success rate for women undergoing embryo transfer by transcutaneous
      electrical acupoint stimulation: a prospective randomized placebo-controlled
      study.
AB  - OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint
      stimulation (TEAS) on pregnancy rates (PR) in women undergoing ET. DESIGN:
      Prospective, randomized, single-blinded placebo-controlled clinical trial.
      SETTING: Research and laboratory facilities. PATIENT(S): A total of 309 patients,
      less than 45 years old, undergoing cryopreservation embryos transplant or fresh
      cycle IVF with or without intracytoplasmic sperm injection (ICSI).
      INTERVENTION(S): The subjects were randomly allocated to three groups: mock TEAS
      treatment: 30 minutes after ET (group I, n = 99); single TEAS treatment: 30
      minutes after ET (group II, n = 110); and double TEAS treatments: 24 hours before
      ET and 30 minutes after ET (group III, n = 100). MAIN OUTCOME MEASURE(S):
      Clinical PR, embryos implantation rate, live birth rate. RESULT(S): The clinical
      PR, embryos implantation rate, and live birth rate of group I (29.3%, 15.0%, and
      21.2%, respectively) were significantly lower than those in group II (42.7%,
      25.7%, and 37.3%, respectively) and group III (50.0%, 25.9%, and 42.0%,
      respectively). CONCLUSION(S): Transcutaneous electrical acupoint stimulation,
      especially double TEAS, significantly improved the clinical outcome of ET.

PMID- 21862002
TI  - Comment on GnRH analogue cotreatment with chemotherapy for preservation of
      ovarian function.

PMID- 21862004
TI  - GI perforation associated with bevacizumab.

PMID- 21862005
TI  - Clinical outcomes and risk factors for technical and clinical failures of self
      expandable metal stent insertion for malignant colorectal obstruction.
AB  - BACKGROUND: Although self-expandable metal stent (SEMS) insertion is widely used
      for relief of malignant colorectal obstructions, the immediate technical and
      clinical failure rates of SEMSs and the associated risk factors remain largely
      unknown. OBJECTIVE: To identify rates and factors predictive of technical and
      clinical failure of SEMSs when their use is attempted for the decompression of
      malignant colorectal obstruction. DESIGN: Retrospective chart review. SETTING: A
      tertiary-care academic medical center in South Korea. PATIENTS: This study
      involved a total of 412 patients with malignant colorectal obstruction in whom
      SEMS insertion was attempted. INTERVENTION: Placement of colonic SEMSs. MAIN
      OUTCOME MEASUREMENTS: Technical success and immediate and long-term clinical
      success rates. RESULTS: Technical and clinical failures were found in 36 of 276
      patients (13.0%) and 39 of 240 patients (16.3%) in the palliative group,
      respectively, and in 3 of 136 patients (2.2%) and 7 of 133 patients (5.3%) in the
      preoperative group, respectively. Factors associated with technical failure were
      extracolonic origin of tumor, the presence of carcinomatosis, and a proximal
      obstruction site. Factors associated with long-term clinical failure in the
      palliative group were combined dilation procedure, no additional chemotherapy,
      and extracolonic origin of the tumor. In the preoperative group, only older
      patients had both higher technical failure and clinical failure rates.
      LIMITATIONS: This was a single-institution, retrospective analysis. CONCLUSION:
      Although colorectal SEMS placement is generally safe and effective, it is
      associated with clinically important technical and clinical failure rates. The
      identification of risk factors for the failure of colorectal SEMSs found in this
      study might help physicians decide between surgical decompression and endoscopic
      stenting in patients with malignant colorectal obstruction.

PMID- 21862006
TI  - Design of a self-tuning regulator for temperature control of a polymerization
      reactor.
AB  - The temperature control of a polymerization reactor described by Chylla and
      Haase, a control engineering benchmark problem, is used to illustrate the
      potential of adaptive control design by employing a self-tuning regulator
      concept. In the benchmark scenario, the operation of the reactor must be
      guaranteed under various disturbing influences, e.g., changing ambient
      temperatures or impurity of the monomer. The conventional cascade control
      provides a robust operation, but often lacks in control performance concerning
      the required strict temperature tolerances. The self-tuning control concept
      presented in this contribution solves the problem. This design calculates a
      trajectory for the cooling jacket temperature in order to follow a predefined
      trajectory of the reactor temperature. The reaction heat and the heat transfer
      coefficient in the energy balance are estimated online by using an unscented
      Kalman filter (UKF). Two simple physically motivated relations are employed,
      which allow the non-delayed estimation of both quantities. Simulation results
      under model uncertainties show the effectiveness of the self-tuning control
      concept.

PMID- 21862007
TI  - Bilateral control of master-slave manipulators with constant time delay.
AB  - This paper presents a novel teleoperation controller for a nonlinear master-slave
      robotic system with constant time delay in communication channel. The proposed
      controller enables the teleoperation system to compensate human and environmental
      disturbances, while achieving master and slave position coordination in both free
      motion and contact situation. The current work basically extends the passivity
      based architecture upon the earlier work of Lee and Spong (2006) [14] to improve
      position tracking and consequently transparency in the face of disturbances and
      environmental contacts. The proposed controller employs a PID controller in each
      side to overcome some limitations of a PD controller and guarantee an improved
      performance. Moreover, by using Fourier transform and Parseval's identity in the
      frequency domain, we demonstrate that this new PID controller preserves the
      passivity of the system. Simulation and semi-experimental results show that the
      PID controller tracking performance is superior to that of the PD controller
      tracking performance in slave/environmental contacts.

PMID- 21862008
TI  - Orthoplastics: an integral evolution within comprehensive trauma care.

PMID- 21862009
TI  - Ethiopia's assessment of emergency obstetric and newborn care: setting the gold
      standard for national facility-based assessments.
AB  - OBJECTIVE: To describe the methods used to implement Ethiopia's 2008 emergency
      obstetric and newborn care services (EmONC) assessment; highlight how the
      collaborative process contributed to immediate integration of results into
      national and subnational planning; and explain how the experience informed the
      development of a set of tools providing best practices and guidelines for other
      countries conducting similar assessments. METHODS: A team of maternal and newborn
      health experts from the Federal Ministry of Health (FMOH), the United Nations
      Children's Fund (UNICEF), the World Health Organization (WHO), and the United
      Nations Population Fund (UNFPA), together with representatives from the Ethiopian
      Society of Obstetricians and Gynecologists, provided technical guidance for the
      18-month process and facilitated demand for and use of the assessment results.
      Eighty-four trained data collectors administered 9 data collection modules in 806
      public and private facilities. Field work and data were managed by a private firm
      who, together with the core team, implemented a multi-layered plan for data
      quality. Columbia University's Averting Maternal Death and Disability Program
      provided technical assistance. RESULTS: Results were published in national and
      regional reports and in 1-page facility factsheets informing subnational planning
      activities. Assessment results-which have been published in journal articles
      informed water infrastructure improvements, efforts to expand access to magnesium
      sulfate, and FMOH and UN planning documents. The assessment also established a
      permanent database for future monitoring of the health system, including
      geographic locations of surveyed facilities. CONCLUSION: Ethiopia's assessment
      was successful largely because of active local leadership, a collaborative
      process, ample financial and technical support, and rapid integration of results
      into health system planning.

PMID- 21862010
TI  - Clinical features of 17 cases of placental site trophoblastic tumor.

PMID- 21862011
TI  - Urban sustainability and nursing: a personal view.

PMID- 21862013
TI  - The antioxidant HDL-associated paraoxonase-1 (PON1) attenuates diabetes
      development and stimulates beta-cell insulin release.
AB  - OBJECTIVE: To analyze the direct effects of paraoxonase-1 (PON1) on diabetes
      development and on beta-cell insulin release. METHODS AND RESULTS: Injection of
      rePON1 to mice, prior to STZ-induced diabetes, resulted in reduced incidence of
      diabetes, as well as, in higher serum insulin levels. Incubation of beta-cells
      with PON1 also dose-dependently increased insulin secretion and its cellular
      content. PON1 increased cell survival under high glucose levels, but not under
      high STZ concentrations. The addition of the PON1 carrier in the circulation -
      HDL, to betaTC3 cell line, had an additive effect on PON1-induced insulin
      secretion. PON1 administration to mice or incubation with beta-cells was
      associated with a substantial decreased oxidative stress. Just like PON1, the
      dietary anti-oxidants, pomegranate juice, punicalagin (major polyphenol in
      pomegranate) or vitamin E, also increased insulin release from betaTC3, but
      unlike PON1, failed to increase insulin cellular content, suggesting a possible
      role for PON1 in insulin biosynthesis, separately from PON1 antioxidative effect.
      Both, PON1 catalytic activity and PON1 association to HDL, were not required for
      PON1 stimulation of insulin release from beta-cells. However, the PON1 free
      sulfhydryl group was shown to be essential for insulin release by PON1, as
      blocking the PON1 SH group, abolished PON1 stimulatory effect on insulin
      secretion. CONCLUSION: PON1 is a potent anti-diabetic enzyme that exerts this
      protection against diabetes through its antioxidative, as well as via its insulin
      stimulation properties on beta-cells.

PMID- 21862012
TI  - Pioglitazone enhances cholesterol efflux from macrophages by increasing
      ABCA1/ABCG1 expressions via PPARgamma/LXRalpha pathway: findings from in vitro
      and ex vivo studies.
AB  - OBJECTIVE: Pioglitazone, a peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist, reportedly reduces cardiovascular events in diabetic
      patients. ATP cassette binding transporters (ABC) A1 and G1 are pivotal molecules
      for cholesterol efflux (ChE) from macrophages and high density-lipoprotein
      biogenesis, and the A1 transporter is regulated by a PPARgamma-liver receptor X
      (LXR) pathway. Also, pioglitazone induces ABCG1 expression, though the exact
      mechanism remains unclear. We therefore investigated the effects of pioglitazone
      on ABCA1/G1 expression in vitro and ex vivo. METHODS: The effects of pioglitazone
      on ChE and ABCA1/G1 expressions in macrophages were assessed. Then, mRNA was
      quantified in macrophages when PPARgamma/LXR inhibition by siRNA or
      overexpression of oxysterol sulfotransferase was performed. ABCA1/G1 promoter
      activity with mutated LXR-responsive elements was also measured. As an ex vivo
      study, 15 type 2 diabetic patients were administered pioglitazone or placebo, and
      ChE assays and protein expressions were determined using macrophages cultured
      with the corresponding sera. RESULTS: Pioglitazone increased LXRalpha/ABCA1/G1
      expressions, which enhanced ChE from macrophages. Inhibition of PPARgamma/LXR
      pathways revealed that LXR was primarily involved in pioglitazone's
      transactivation of ABCA1 but only partially involved for ABCG1. Promoter assays
      showed that ABCG1 was regulated more by the promoter in intron 4 than that
      upstream of exon 1 but both promoters were responsive to LXR activation. Sera
      obtained after pioglitazone treatment promoted ChE and ABCA1/G1 expressions in
      macrophages. CONCLUSION: Pioglitazone enhanced ChE from macrophages by increasing
      ABCA1/G1 in LXR-dependent and -independent manners. Our comparable in vitro and
      ex vivo results shed new light on pioglitazone's novel anti-atherogenic property.

PMID- 21862014
TI  - Biomarkers to predict clinical progression in small vessel disease strokes:
      prognostic role of albuminuria and oxidized LDL cholesterol.
AB  - OBJECTIVE: Clinical progression in lacunar strokes (LS) is an unpredictable and
      fearful complication. Endothelial dysfunction (ED) is believed to be the first
      step in the pathophysiology of LS therefore we aimed to analyze the association
      of three markers of ED: albuminuria, von Willebrand factor (vWF), and oxidized
      LDL cholesterol (ox-LDL) with LS progression. METHODS: From December 2007 to
      December 2010, 127 LS patients admitted within 6 h of symptom onset were
      prospectively assessed. Progression was defined as initial NIHSS score worsening
      >=4 points within the first 72 h. Analysis of vWF and ox-LDL was done at
      admission. Albuminuria was measured in the first morning spot urine. Association
      between 3 biomarkers and progression was tested using logistic regression
      analysis. Other clinical variables of interest were also studied. Discriminative
      power was analyzed with a receiver operator curve. RESULTS: Twenty-two patients
      (17.3%) progressed. Progression was associated with worse outcome at 90 days.
      Albuminuria and ox-LDL were associated in univariate analysis; vWF was not.
      Adjusted OR were: ox-LDL [OR: 1.03; 95% CI: 1.01-1.07, p=0.019], albuminuria [OR:
      2.07; 95% CI: 1.04-4.13, p=0.039]. Association was linear without a cut-off
      point. Clinical variables were not associated with progression. The model
      including albuminuria and ox-LDL had a good predictive value [AUC: 0.80 [0.70
      0.89)]. CONCLUSIONS: Albuminuria and ox-LDL levels are independently associated
      with higher risk of progression in LS. The lack of reliable clinical predictors
      makes biomarker research a priority to improve progression detection in this
      subtype of ischemic strokes.

PMID- 21862015
TI  - Human atherosclerotic plaque lipid extract promotes expression of proinflammatory
      factors in human monocytes and macrophage-like cells.
AB  - OBJECTIVE: The potential of the atherogenic human carotid plaque to stimulate the
      inflammatory process was examined in human monocytes and macrophages, in vitro.
      METHODS AND RESULTS: Exposure of monocytes to human carotid plaque lipid extract
      (LE) elevated the transcription level of the proinflammatory cytokines,
      interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha, by 2.9 and 100.2
      fold, respectively (as determined by real time PCR), and induced TNF-alpha
      secretion (as measured by enzyme-linked immunosorbent assay). Furthermore, LE
      caused an increase of 1.3-3.1 fold in the mRNA expression of the proinflammatory
      factors, IL-1beta, IL-6, TNF-alpha, cyclooxygenase-2 and intercellular adhesion
      molecule-1, in macrophage-like cells. In order to investigate the proinflammatory
      components in the extract, two fractions, obtained by silica gel separation of
      LE, were characterized. The cholesterol-oxysterol rich fraction was found to have
      the most significant proinflammatory effect. It caused an increase in TNF-alpha
      expression in monocytes, and upregulated IL-6, TNF-alpha, intercellular adhesion
      molecule-1 and cyclooxygenase 2 by 1.5-2.5 fold in macrophages. The triglyceride
      fraction had almost no effect on the cells. CONCLUSIONS: The human carotid plaque
      lipid extract was demonstrated to promote inflammation, in vitro. These data
      support the atherogenic character of the plaque and imply that its lipid
      composition may have ramifications on the progress of atherosclerosis.

PMID- 21862016
TI  - Adventitial gene transfer of VEGFR-2 specific VEGF-E chimera induces MCP-1
      expression in vascular smooth muscle cells and enhances neointimal formation.
AB  - BACKGROUND: The role of vascular endothelial growth factors (VEGFs) in neointimal
      formation has been controversial. VEGF receptor (R)-2 signaling pathway is
      crucial in bringing about the effects of VEGFs including vasodilatation,
      endothelial cell migration and proliferation. In this study we have used an
      established adventitial gene transfer technique, in vitro studies and a novel
      VEGF-E/PlGF chimera that binds specifically to VEGFR-2, to investigate the role
      of VEGFR-2 in neointimal formation. METHODS: Intimal hyperplasia was induced in
      the carotid arteries of cholesterol fed male New Zealand White rabbits using a
      silastic collar. Adenoviral vectors encoding VEGF-E chimera (1*10(9) pfu/ml) were
      transferred to the adventitia of the carotid arteries either alone or together
      with adenoviruses encoding soluble VEGFR-2 (sVEGFR-2). Adenoviruses encoding LacZ
      were used as controls. All animals were sacrificed 7 days after the gene
      transfer. RESULTS: Significant increases in neointimal formation, proliferating
      cells, inflammatory responses and adventitial angiogenesis were observed in the
      VEGF-E chimera transduced arteries. The number of medial smooth muscle cells
      expressing VEGFR-2 was significantly (p<0.001) higher. MCP-1 mRNA levels were
      significantly (p<0.01) increased in the VEGF-E chimera transduced arteries and
      transduced rabbit aortic smooth muscle cells (p<0.05). Soluble VEGFR-2 (sVEGFR-2)
      significantly inhibited VEGF-E chimera induced neointimal formation (p<0.01),
      cellular proliferation (p<0.01), inflammatory responses (p<0.01) and adventitial
      angiogenesis (p<0.01). CONCLUSIONS: The results indicate that VEGFR-2 mediated
      signaling could aggravate neointimal formation and suggest a potential
      therapeutic role of sVEGFR-2 in inhibiting neointimal formation and adventitial
      angiogenesis.

PMID- 21862017
TI  - Vulnerable plaque features on coronary CT angiography as markers of inducible
      regional myocardial hypoperfusion from severe coronary artery stenoses.
AB  - OBJECTIVE: We explored whether the presence of 3 known features of plaque
      vulnerability on coronary CT angiography (CCTA)--low attenuation plaque content
      (LAP), positive remodeling (PR), and spotty calcification (SC)--identifies
      plaques associated with greater inducible myocardial hypoperfusion measured by
      myocardial perfusion imaging (MPI). METHODS: We analyzed 49 patients free of
      cardiac disease who underwent CCTA and MPI within a 6-month period and were found
      on CCTA to have focal 70-99% stenosis from predominantly non-calcified plaque in
      the proximal or mid segment of 1 major coronary artery. Presence of LAP (<= 30
      Hounsfield Units), PR (outer wall diameter exceeds proximal reference by >= 5%),
      and SC (<= 3 mm long and occupies <= 90 degrees  of cross-sectional artery
      circumference) was determined. On MPI, reversible hypoperfusion in the myocardial
      territory corresponding to the diseased artery was quantified both as percentage
      of total myocardium (RevTPD(ART)) by an automatic algorithm and as summed
      difference score (SDS(ART)) by two experienced readers. RevTPD(ART)>= 3% and
      SDS(ART)>= 3 defined significant inducible hypoperfusion in the territory of the
      diseased artery. RESULTS: Plaques in patients with RevTPD(ART)>= 3% more
      frequently exhibited LAP (70% vs. 14%, p < 0.001) and PR (70% vs. 24%, p = 0.001)
      but not SC (55% vs. 34%, p = 0.154). RevTPD(ART) increased from 1.3 +/- 1.2% in
      arteries with LAP-/PR- plaques to 3.2 +/- 4.3% with LAP+/PR- or LAP-/PR+ plaques
      to 8.3 +/- 2.4% with LAP+/PR+ plaques (p < 0.001); SDS(ART) showed a similar
      increase: 0.3 +/- 0.7 to 2.3 +/- 2.8 to 6.0 +/- 3.8 (p < 0.001). Using the same
      LAP/PR categorization, there was a marked increase in the frequency of
      significant hypoperfusion as determined by both RevTPD(ART)>= 3% (1/19 to 10/21
      to 9/9, p < 0.001) and SDS(ART)>= 3 (1/19 to 8/21 to 8/9, p < 0.001). LAP and PR,
      but not SC, were strong predictors of RevTPD(ART) and SDS(ART) in regression
      models adjusting for potential confounders. CONCLUSIONS: Presence of low
      attenuation plaque and positive remodeling in severely stenotic plaques on CCTA
      is strongly predictive of myocardial hypoperfusion and may be useful in assessing
      the hemodynamic significance of such lesions.

PMID- 21862018
TI  - Increased atherosclerosis and vascular smooth muscle cell activation in AIF-1
      transgenic mice fed a high-fat diet.
AB  - Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, scaffold signal
      transduction protein constitutively expressed in inflammatory cells, but
      inducible in vascular smooth muscle cells (VSMCs) in response to injury or
      inflammatory stimuli. Although several basic science and population studies have
      reported increased AIF-1 expression in human and experimental atherosclerosis, a
      direct causal effect of AIF-1 expression on development of atherosclerosis has
      not been reported. The purpose of this study is to establish a direct
      relationship between AIF-1 expression and development of atherosclerosis. AIF-1
      expression is detected VSMC in atherosclerotic lesions from ApoE(-/-) mice, but
      not normal arteries from wild-type mice. AIF-1 expression can be induced in
      cultured VSMC by stimulation with oxidized LDL (ox-LDL). Transgenic mice in which
      AIF-1 expression is driven by the G/C modified SM22 alpha promoter to restrict
      AIF-1 expression to VSMC develop significantly increased atherosclerosis compared
      with wild-type control mice when fed a high-fat diet (P=0.022). Cultured VSMC
      isolated from Tg mice demonstrated significantly increased migration in response
      to ox-LDL compared with matched controls (P<0.001). VSMC isolated from Tg mice
      and cultured human VSMC which over express AIF-1 demonstrated increased
      expression of MMP-2 and MMP-9 mRNA and protein and increased NF-kappaB activation
      in response to ox-LDL as compared with wild-type control mice. VSMC which over
      express AIF-1 have significantly increased uptake of ox-LDL, and increased CD36
      expression. Together, these data suggest a strong association between AIF-1
      expression, NF-kappaB activation, and development of experimental
      atherosclerosis.

PMID- 21862020
TI  - A constitutive model for vascular tissue that integrates fibril, fiber and
      continuum levels with application to the isotropic and passive properties of the
      infrarenal aorta.
AB  - A fundamental understanding of the mechanical properties of the extracellular
      matrix (ECM) is critically important to quantify the amount of macroscopic stress
      and/or strain transmitted to the cellular level of vascular tissue. Structural
      constitutive models integrate histological and mechanical information, and hence,
      allocate stress and strain to the different microstructural components of the
      vascular wall. The present work proposes a novel multi-scale structural
      constitutive model of passive vascular tissue, where collagen fibers are
      assembled by proteoglycan (PG) cross-linked collagen fibrils and reinforce an
      otherwise isotropic matrix material. Multiplicative kinematics account for the
      straightening and stretching of collagen fibrils, and an orientation density
      function captures the spatial organization of collagen fibers in the tissue.
      Mechanical and structural assumptions at the collagen fibril level define a piece
      wise analytical stress-stretch response of collagen fibers, which in turn is
      integrated over the unit sphere to constitute the tissue's macroscopic mechanical
      properties. The proposed model displays the salient macroscopic features of
      vascular tissue, and employs the material and structural parameters of clear
      physical meaning. Likewise, the constitutive concept renders a highly efficient
      multi-scale structural approach that allows for the numerical analysis at the
      organ level. Model parameters were estimated from isotropic mean-population data
      of the normal and aneurysmatic aortic wall and used to predict in-vivo stress
      states of patient-specific vascular geometries, thought to demonstrate the
      robustness of the particular Finite Element (FE) implementation. The collagen
      fibril level of the multi-scale constitutive formulation provided an interface to
      integrate vascular wall biology and to account for collagen turnover.

PMID- 21862019
TI  - Activation of human vascular cells decreases their expression of transforming
      growth factor-beta.
AB  - OBJECTIVE: Despite pro-fibrotic effects, transforming growth factor (TGF)-beta
      prevents arteriosclerosis by suppressing effector leukocytes and promoting smooth
      muscle differentiation. However, previous observations of increased TGF-beta
      expression in arteriosclerotic plaques are not consistent with that of an
      effective protective factor. We investigated the expression, regulation, and
      responses of TGF-beta in human arterial tissues and cells. METHODS AND RESULTS:
      The expression of TGF-beta by intrinsic vascular cells was lower in
      arteriosclerotic than non-diseased coronary arteries. Activation of resident and
      infiltrating leukocytes did not elicit TGF-beta production from coronary artery
      segments in organ culture. Instead, the basal expression of TGF-beta by coronary
      arteries decreased after vessel procurement and ex vivo culture. Activation of
      cultured smooth muscle cells and endothelial cells with phorbol ester and
      ionophore also decreased TGF-beta expression. Isolated cell types representing
      those found in the artery wall were all capable of signaling in response to TGF
      beta, however production of the cytoprotective molecule, interleukin-11 was cell
      type-dependent and restricted to smooth muscle cells and fibroblasts. Interleukin
      11 reduced smooth muscle cell apoptosis to T cell effectors. CONCLUSIONS:
      Inflammation and cellular activation diminish the basal expression of TGF-beta by
      quiescent human vascular cells. Induction of interleukin-11 may contribute to the
      anti-arteriosclerotic actions of TGF-beta.

PMID- 21862021
TI  - Derivatization of the tricarboxylic acid cycle intermediates and analysis by
      online solid-phase extraction-liquid chromatography-mass spectrometry with
      positive-ion electrospray ionization.
AB  - The analysis of cellular metabolic processes is of fundamental biological
      interest. Cellular metabolites, such as the intermediates of the tricarboxylic
      acid (TCA) cycle, provide essential information about the metabolic state of the
      cell. Not only is the TCA cycle a key factor in the energy regulation within
      aerobic cells, it possibly also plays a role in cell signaling. This paper
      describes a novel derivatization strategy, using the empirically selected N
      methyl-2-phenylethanamine as derivatization reagent with a carbodiimide as co
      reagent, for the selective derivatization of carboxylic acids, such as the di-
      and tri-carboxylic acids of the TCA cycle. Optimization of the derivatization
      protocol is described. This procedure enables analysis of the derivatives using
      on-line solid-phase extraction and reversed-phase liquid chromatography in
      combination with sensitive positive-ion electrospray ionization mass
      spectrometry. The complete procedure, involving the use of core-shell silica
      column material, allows the rapid analysis of TCA cycle intermediates in sample
      matrices, here shown for pig heart tissue extracts, with a good linearity over 3
      4 orders of magnitude. Detection limits range from 12 to 1000 nM, depending on
      the analyte.

PMID- 21862022
TI  - Cation-selective exhaustive injection and sweeping micellar electrokinetic
      chromatography for the analysis of methadone and its metabolites in serum of
      heroin addicts.
AB  - Methadone (MET) metabolism has been largely demonstrated with a high inter
      individual variability and, therefore, quantification of MET is very important
      for therapeutic drug monitoring. A cation-selective exhaustive injection and
      sweeping MEKC (CSEI-Sweeping) was first developed to analyze MET and its two
      metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl
      5-methyl-3,3-diphenyl-1-pyrroline (EMDP), in human serum. After pretreatment, the
      samples were electrokinetically injected into capillary (10 kV, 500s) and swept
      by the separation phosphate buffer (100 mM, pH 4.0) containing 20%
      tetrahydrofuran and 100 mM SDS at -15 kV. The LODs were 200 pg/mL for MET and
      EMDP, and 400 pg/mL for EDDP. Ten volunteers were administered MET (5.0-120.0
      mg/day) orally for 84 days and serum samples were taken after the daily dose of
      MET (days 1, 2, 7, 14, 28, 56 and 84) individually. This method was used for
      monitoring MET and its metabolites in heroin addicts and for pharmacokinetic
      investigations.

PMID- 21862023
TI  - Enhancing sensitivity and selectivity in the determination of aldehydes in olive
      oil by use of a Tenax TA trap coupled to a UV-ion mobility spectrometer.
AB  - A Tenax TA trap was coupled to an ion mobility spectrometer in order to improve
      basic analytical properties such as sensitivity and selectivity. The analytical
      performance of this combination was assessed in the determination of volatile
      aldehydes between 3 and 6 carbon atoms present in olive oil. The aldehydes were
      extracted and adsorbed into the trap, from which they were thermally desorbed for
      analysis by UV-Ion Mobility Spectrometry (UV-IMS). Sensitivity was increased by
      the preconcentration step and selectivity by the combination of temperature
      programmed thermal desorption and the ability of the ion mobility spectrometer to
      monitor the desorbed analytes in real time. The limits of detection obtained were
      lower than 0.3 mg kg(-1) and the relative standard deviation lower than 10%. A
      one-way analysis of variance (ANOVA) was used to identify significant differences
      between olive oil grades in terms of peak heights for the target aldehydes.

PMID- 21862024
TI  - A study on retention "projection" as a supplementary means for compound
      identification by liquid chromatography-mass spectrometry capable of predicting
      retention with different gradients, flow rates, and instruments.
AB  - Using current data analysis techniques, even the most advanced LC-MS
      instrumentation can identify only a small fraction of compounds found in typical
      biological extracts. Augmenting MS information with HPLC retention information
      allows many more to be identified. In fact, our calculations indicate that a
      quadrupole MS is able to identify more compounds than an FTICR-MS when the
      quadrupole spectrum is augmented with retention information. Unfortunately,
      retention information is extremely difficult to harness for compound
      identification. Here, we demonstrate the first use of isocratic data measured on
      one LC-MS to "project" gradient retention on to different LC-MS systems. Using 35
      chemically diverse solutes chosen to encompass the full range of reversed-phase
      alkylsilica interactions, and using experimental conditions typical of
      metabolomics experiments, gradient retention was projected from one instrument to
      another with only 1.2-2.6% error-enough accuracy to considerably improve compound
      identification. Besides accounting for nonlinear relationships of retention
      versus solvent composition as well as dead time versus solvent composition,
      accounting for the precise shape of the gradient profile (not just the dwell
      volume) improved projection accuracy on one instrument by up to 4 fold whereas
      flow rate non-idealities likely caused considerable error on the other
      instrument. Thus, these two factors must be taken into account to accurately
      project retention on diverse instrumentation.

PMID- 21862025
TI  - Separation of exenatide analogue mono-PEGylated with 40 kDA polyethylene glycol
      by cation exchange chromatography.
AB  - Random PEGylation usually resulted in product mixtures composed of mono-PEGylated
      isomers and multi-PEGylated attachments. Generally in PEGylation research,
      separation of the mono-PEGylated isomers was the prerequisite for finding the
      optimal PEGylation site. However, when peptides or proteins were PEGylated with
      polyethylene glycol as large as 40 kDA, the physicochemical properties like
      hydrophobicity and molecular size of the isomers would become too similar to make
      the routine separation methods, like RP-HPLC, size-exclusion chromatography, SDS
      PAGE and capillary isoelectric focusing invalid. This article presented a useful
      method of successfully separating exenatide analogue (an incretin for diabetic
      therapy) isomers mono-PEGylated with 40 kDA polyethylene glycol by cation
      exchange chromatography, which would be a powerful tool for the PEGylation
      research.

PMID- 21862026
TI  - Characterization of an unusual adsorption behavior of racemic methyl-mandelate on
      a tris-(3,5-dimethylphenyl) carbamoyl cellulose chiral stationary phase.
AB  - An interesting adsorption behavior of racemic methyl mandelate on a tris-(3,5
      dimethylphenyl)carbamoyl cellulose chiral stationary phase was theoretically and
      experimentally investigated. The overloaded band of the more retained enantiomer
      had a peculiar shape indicating a type V adsorption isotherm whereas the
      overloaded band of the less retained enantiomer had a normal shape indicating a
      type I adsorption behavior. For a closer characterization of this separation,
      adsorption isotherms were determined and analyzed using an approach were
      Scatchard plots and adsorption energy distribution (AED) calculations are
      combined for a deeper analysis. It was found that the less retained enantiomer
      was best described by a Toth adsorption isotherm while the second one was best
      described with a bi-Moreau adsorption isotherm. The latter model comprises non
      ideal adsorbate-adsorbate interactions, providing an explanation to the non-ideal
      adsorption of the more retained enantiomer. Furthermore, the possibility of using
      the Moreau model as a local model for adsorption in AED calculations was
      evaluated using synthetically generated raw adsorption slope data. It was found
      that the AED accurately could predict the number of adsorption sites for the
      generated data. The adsorption behavior of both enantiomers was also studied at
      several different temperatures and found to be exothermic; i.e. the adsorbate
      adsorbate interaction strength decreases with increasing temperature. Stochastic
      analysis of the adsorption process revealed that the average amount of
      adsorption/desorption events increases and the sojourn time decreases with
      increasing temperature.

PMID- 21862027
TI  - Comparison of the performance of conventional, temperature-controlled, and
      ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction
      combined with high-performance liquid chromatography in analyzing pyrethroid
      pesticides in honey samples.
AB  - This research paper presents a comparative study of the performance of
      conventional, ultrasound-assisted (UA), and temperature-controlled (TC) ionic
      liquid (IL) dispersive liquid-phase microextraction (IL-DLLME). Various
      parameters that affect extraction efficiency, such as type and volume of
      extraction and disperser solvent, centrifugation time, salt addition, effect of
      temperature on TC-IL-DLLME, and effect of sonication time on UA-IL-DLLME, were
      evaluated. UA-IL-DLLME was found to provide the best extraction efficiency. Under
      optimized conditions, great enrichment factors (506-515) and good recoveries
      (101.2-103.0%) were obtained by analyte extraction in real samples. The limit of
      detections (LODs) ranged from 0.21 to 0.38 MUg L(-1). Good linearity was obtained
      in the range of 0.5-200 MUg L(-1) for ethofenprox and tetramethrin, and 1-200 MUg
      L(-1) for meperfluthrin and alpha-cypermethrin. Based on optimized conditions,
      the UA-IL-DLLME method was applied and combined with high-performance liquid
      chromatography with diode array detection (HPLC-DAD) to determine the presence of
      ethofenprox, tetramethrin, meperfluthrin, and alpha-cypermethrin in honey
      samples.

PMID- 21862028
TI  - High performance liquid chromatography column packings with deliberately
      broadened particle size distribution: relation between column performance and
      packing structure.
AB  - The effect of the addition of 25%, 50% and 75% (weight percent, wt%) of larger
      particles (resp. 3 and 5 MUm) to a commercial batch of 1.9 MUm particles has been
      investigated as an academic exercise to study the effects of particle size
      distribution on the kinetic performance of packed bed columns in a magnified way.
      Comparing the performance of the different mixtures in a kinetic plot, it could
      be irrefutably shown that the addition of larger particles to a commercial batch
      of small particles cannot be expected to lead to an improved kinetic performance.
      Whereas the addition of 25 wt% of larger particles still only has a minor
      negative effect, a significantly deteriorated performance is obtained when 50 or
      75 wt% of larger particles are added. In this case, separation impedance number
      increases up to 200% were observed. Studying the packing structure through
      computational packing simulations, together with the experimental determination
      of the external porosity, helped in understanding the obtained results. This
      showed that small particles tend to settle in the flow-through pores surrounding
      the larger particles, leading to very high packing densities (external porosities
      as low as 32% were observed) and also negatively influencing the column
      permeability as well as the band broadening (because of the broadened flow
      through pore size range).

PMID- 21862030
TI  - Fabrication of 2D photonic crystals using block copolymer patterns on as grown
      LEDs.
AB  - Di-block copolymer polystyrene-block-polymethyl methacrylate (PS-b-PMMA) was used
      to make patterns over a large area of as grown LEDs. The polymer patterns on LEDs
      surface could be transferred to the underlying p-GaN, the topmost layer of as
      grown LEDs by both reactive ion etching (RIE) and photo-enhanced chemical (PEC)
      etching. Removal of remaining polymer chains results in patterned LEDs which
      shows higher light extraction efficiency. In our experiment, much higher
      intensity for patterned LEDs in both photoluminescence (PL) and
      electroluminescence (EL) data plot were found. Similar improvements were found in
      I-V and L-I curves for patterned LEDs.

PMID- 21862029
TI  - Selective enrichment of the degradation products of organophosphorus nerve agents
      by zirconia based solid-phase extraction.
AB  - Selective extraction and enrichment of nerve agent degradation products has been
      achieved using zirconia based commercial solid-phase extraction cartridges.
      Target analytes were O-alkyl alkylphosphonic acids and alkylphosphonic acids, the
      environmental markers of nerve agents such as sarin, soman and VX. Critical
      extraction parameters such as modifier concentration, nature and volume of
      washing and eluting solvents were investigated. Amongst other anionic compounds,
      selectivity in extraction was observed for organophosphorus compounds. Recoveries
      of analytes were determined by GC-MS which ranged from 80% to 115%. Comparison of
      zirconia based solid-phase extraction method with anion-exchange solid-phase
      extraction revealed its selectivity towards phosphonic acids. The limits of
      detection (LOD) and limit of quantification (LOQ) with selected analytes were
      achieved down to 4.3 and 8.5 ng mL(-1), respectively, in selected ion monitoring
      mode.

PMID- 21862031
TI  - Fabrication of superhydrophilic poly(styrene-alt-maleic anhydride)/silica hybrid
      surfaces on poly(vinylidene fluoride) membranes.
AB  - Superhydrophilic organic/inorganic hybrid surfaces have been fabricated on blend
      membranes of poly(vinylidene fluoride) (PVDF) and poly(styrene-alt-maleic
      anhydride) (SMA). The blend membranes were prepared from PVDF/SMA mixed solution
      with N,N-dimethylacetamide (DMAc) as solvent by immersion-precipitation phase
      inversion process. The gained blend membranes were immersed into gamma
      aminopropyltriethoxysilane (APTS) solution to generate SMA/silica hybrid surfaces
      by the reaction between anhydrides and APTS. The hybrid surfaces chemical
      compositions, morphologies and hydrophilicity were investigated in detail. It
      demonstrates that the hybrid surfaces possess micro-nano hierarchical structure
      and display superhydrophilicity property and good stability. Finally, the
      reaction and formation mechanism of the superhydrophilicity hybrid surface was
      discussed.

PMID- 21862032
TI  - Large-scale synthesis of ZnO balls made of fluffy thin nanosheets by simple
      solution process: structural, optical and photocatalytic properties.
AB  - This paper reports a large-scale synthesis of ZnO balls made of fluffy thin ZnO
      nanosheets by simple solution process at low-temperature of 65+/-2 degrees C. The
      synthesized ZnO structures were characterized in detail in terms of their
      morphological, structural, optical and photocatalytic properties. The detailed
      morphological characterizations, done by field emission scanning electron
      microscopy (FESEM) and transmission electron microscopy (TEM), confirmed that the
      synthesized products are ZnO balls which are made by accumulation of hundreds of
      thin ZnO nanosheets. Interestingly, it is seen that the nanosheets are arranged
      in such a special fashion that they made ball-like morphologies. Detailed
      structural examinations revealed that of as-synthesized ZnO products are well
      crystalline and possessing wurtzite hexagonal phase. The optical property,
      measured by UV-Visible spectroscopy, substantiated good optical properties for as
      synthesized ZnO balls. The as-synthesized ZnO balls were utilized as an efficient
      photocatalysts for the photocatalytic degradation of methylene blue (MB) dye.
      Almost complete degradation of MB was observed in presence of ZnO balls composed
      of nanosheets within 70 min under UV-light irradiation. By comparing the
      photocatalytic performance with commercially available TiO(2)-UV-100, it was
      observed that the synthesized ZnO balls exhibited superior photocatalytic
      performance as compared to TiO(2)-UV-100 photocatalyst.

PMID- 21862033
TI  - Central nervous system neuroblastoma in a wild deer (Capreolus capreolus).
AB  - This report describes a central nervous system (CNS) neuroblastoma in a wild deer
      (Capreolus capreolus) of approximate age 10 years. The doe was found in a barn
      with a fractured right forelimb and was shot. The animal was submitted for post
      mortem examination in order to exclude rabies. The tumour was located in the
      midline of the mesencephalon with replacement of thalamus and parts of the
      hypothalamus and infiltration into the adjacent neuroparenchyma and the right
      lateral and third ventricles. Microscopically, the neoplastic cells were arranged
      in sheets and nests forming Homer-Wright- and pseudorosettes.
      Immunohistochemically, the tumour cells expressed neuron-specific enolase,
      synaptophysin, doublecortin and neurofilament. This is the first report of an
      infiltrative CNS neuroblastoma in a wild deer.

PMID- 21862034
TI  - Perseveration and the status of 3-year-olds' knowledge in a card-sorting task:
      evidence from studies involving congruent flankers.
AB  - Infants and young children often perseverate despite apparent knowledge of the
      correct response. Two Experiments addressed questions concerning the status of
      such knowledge in the context of a card-sorting task. In Experiment 1, three
      groups of 3-year-olds sorted bivalent cards one way and then were instructed to
      switch and sort the same cards using new rules under varying conditions of
      support offered by congruent flankers. Although formal aspects of the task such
      as higher-order rule use, stimulus redescription, and dimensional shifting
      remained constant across all conditions, use of the new rules increased with
      parametric increases in environmental support for the use of the new rules. In
      Experiment 2, 3-year-olds were more likely to switch and use new rules when test
      stimuli were flanked by congruent flankers rather than neutral flankers, even
      though both conditions made equivalent demands on attentional inhibition. Thus,
      in both experiments, children's knowledge of the new rules proved to be adequate
      under less demanding conditions but inadequate under more demanding conditions.
      These findings are consistent with the idea that children's knowledge is graded
      in strength rather than present or absent.

PMID- 21862035
TI  - Influencing factors and predictors of early improvement in the acute treatment of
      schizophrenia and schizophrenia spectrum disorder.
AB  - BACKGROUND: To examine the influencing factors and predictors of early
      improvement in schizophrenia patients. METHODS: 370 patients suffering from a
      schizophrenia spectrum disorder were examined within a naturalistic multicenter
      study. Early improvement was defined as a >=30% PANSS total score reduction
      within the first two treatment weeks, response as a >=50% improvement of the
      PANSS total score from admission to discharge and remission according to the
      consensus remission criteria. Baseline and course-related variables such as
      positive, negative and depressive symptoms, side effects, functioning and
      subjective well-being were examined regarding their explanatory value for early
      improvement. RESULTS: 46% of the patients were identified to be early improvers.
      Of these, 77% became treatment responder at discharge and 74% achieved the
      consensus remission criteria. Amongst others, early improvers were significantly
      more often first-episode patients (p = 0.009), with a significantly shorter
      duration of current episode (p = 0.024) and a shorter duration of the illness (p
      = 0.0094). A higher PANSS positive subscore (p = 0.0089), a higher score in the
      Strauss-Carpenter-Prognostic Scale (SCPS) (p < 0.0001), less extrapyramidal side
      effects (p = 0.0004) at admission and the development of less extrapyramidal side
      effects within the first two treatment weeks (p = 0.0013) as well as a duration
      of current episode of <=6 months (p = 0.0373) were identified to be significant
      predictors of early improvement. CONCLUSION: Early improvement is associated with
      less illness chronicity and seems to be independent of the type of antipsychotic
      and the antipsychotic dosage applied. The SCPS was found to be a valuable tool to
      detect early improvers already at the initiation of antipsychotic treatment.

PMID- 21862036
TI  - Activation patterns in multiple sclerosis on the Computerized Tests of
      Information Processing.
AB  - RATIONALE: Multiple sclerosis (MS) patients exhibit cognitive deficits that
      negatively impact quality of life. The Relative Consequence Model suggests that
      problems with information processing speed (IPS) may be the basis for many of
      these cognitive difficulties. OBJECTIVE: To investigate, with functional magnetic
      resonance imaging (fMRI), if an IPS task (the Computerized Test of Information
      Processing (CTIP)) would reveal neurophysiological differences between MS
      patients and matched controls. METHODS: Performance and neural activation were
      investigated in twelve cognitively impaired MS patients and 12 matched controls
      as each performed the CTIP. The CTIP measures reaction time (RT) and errors on
      three tasks (simple RT, choice RT and semantic search RT) with increasing
      cognitive demands. RESULTS: Participants demonstrated increased RT with increased
      task complexity. Patients showed longer RTs for the choice RT condition than
      controls but the pattern of performance across tasks did not vary between groups.
      Errors were not significantly different between groups. Imaging results for both
      the choice and the semantic search conditions revealed significant differences
      between groups involving a compensatory increase in activation in MS participants
      compared to controls in prefrontal cortex and right temporal gyri. However, there
      were also areas of decreased activity in MS participants when compared with
      controls in left temporal gyri. CONCLUSIONS: Significantly different neural
      activation patterns between MS patients and controls were associated with IPS, as
      measured by the CTIP.

PMID- 21862037
TI  - Fatigue among stroke patients on long-term follow-up. The Bergen Stroke Study.
AB  - BACKGROUND: To evaluate characteristics and mortality related to post-stroke
      fatigue (PSF). METHODS: All surviving stroke patients admitted to the Stroke
      Unit, Haukeland University Hospital, between February 2006 and November 2008 were
      sent a postal questionnaire including the Fatigue Severity Scale (FSS), the
      hospital anxiety and depression scale (HADSD), and the Barthel Index (BI) at
      least 6 months after stroke onset. Survival among patients returning the
      questionnaire was determined by November 2009. PSF was defined as FSS score >=5.
      RESULTS: Among 377 patients returning the questionnaire, 42.3% had PSF. Logistic
      regression showed that PSF was independently associated with pre-stroke
      depression, leucoaraiosis, myocardial infarction, diabetes mellitus, pain, and
      sleeping disturbances. Mean FSS score was lower among TIA patients than among
      patients with minor cerebral infarction (patients with BI=100) (P=.002). Cox
      regression analysis showed mortality to be associated with PSF. CONCLUSION: There
      is a multifactorial basis for PSF suggesting different therapy options. Cerebral
      lesions may cause PSF in some patients. Post-stroke fatigue is associated with
      higher mortality.

PMID- 21862038
TI  - Mesencephalic midline change on transcranial sonography in early Parkinson's
      disease patients with depression.
AB  - Recently, several studies using transcranial sonography (TCS) have resulted in
      the alteration of the mesencephalic midline in patients with depression. We aimed
      to investigate and compare sonographic abnormalities in the brainstem raphe (BR)
      in patients with Parkinson's disease (PD) and controls, according to presence of
      depression. Study participants totaled 61 patients with PD (29 PD without
      depression, 32 PD with depression) and 41 controls. Results indicated that
      decreased BR echogenicity was much higher in PD patients with depression (PD+D)
      than in those without depression (PD-D). Of the 61 PD patients, 32 (52.4%) had
      depression as diagnosed by psychiatric assessment, and 13 (17.6%) were excluded,
      due to insufficient temporal windows. Based on these results, the use of TCS with
      respect to the mesencephalic midline may be useful in detecting depression, a
      risk factor for the development of PD.

PMID- 21862039
TI  - Editorial comment.

PMID- 21862040
TI  - The relationship between obesity and complications after neonatal circumcision.
AB  - PURPOSE: Penile adhesions with hidden penis and penile skin bridges are
      complications after neonatal circumcision that seem to develop more often in
      overweight children. They could possibly be avoided if there were neonatal
      parameters predicting circumcision complications. We hypothesized that penile
      adhesions with hidden penis and skin bridges may be predicted by the height and
      weight of a newborn. MATERIALS AND METHODS: We performed an institutional review
      board approved case-control study. Boys younger than 5 years who presented for
      evaluation of penile adhesions with hidden penis and/or penile skin bridges after
      newborn circumcision were compared to boys of the same age who were circumcised
      at birth and did not have penile adhesions with hidden penis and/or skin bridges
      when evaluated for cryptorchidism or hernia/hydrocele. Weight for length
      percentiles were compared at birth and at urological evaluation. RESULTS: We
      evaluated 51 patients with penile adhesions and hidden penis after newborn
      circumcision, and compared them to 33 age matched controls. Boys with hidden
      penis had a statistically higher weight for length percentile at birth and at
      urological evaluation. However, in boys with penile skin bridges there was no
      statistical difference in the weight for length percentile at either time.
      CONCLUSIONS: An increased weight for length percentile in male infants before and
      after circumcision may be associated with penile adhesions with hidden penis but
      not penile skin bridges. These parameters should be considered before newborn
      circumcision when counseling parents, and after circumcision since early
      recognition of obesity might indicate the need for diligent genital hygiene to
      try to prevent post-circumcision complications.

PMID- 21862041
TI  - Epididymo-orchitis complicating anorectal malformations: collective review of 41
      cases.
AB  - PURPOSE: Epididymo-orchitis is a devastating complication of imperforate anus.
      Without proper treatment the condition may result in infertility. Nevertheless,
      the exact etiology and optimal management of epididymo-orchitis in anorectal
      malformation are unknown. MATERIALS AND METHODS: Retrospective review of our
      hospital records between 1997 and 2010 identified 6 cases of epididymo-orchitis
      in 82 boys with anorectal malformation. Extensive search of the literature
      revealed 35 additional cases. Clinical details of these 41 patients were analyzed
      using chi-square testing. RESULTS: Epididymo-orchitis occurred predominantly
      (86%) in high or intermediate anorectal malformation with rectourinary fistula.
      Median age at onset of epididymo-orchitis was 6 months and there was no side
      predilection. Urinary tract infection was noted in 54% of patients. Persistent
      mesonephric duct syndrome (27%), urethroejaculatory duct reflux (22%),
      vasovesical ectopia (10%), neurovesical dysfunction (34%) and urethral
      stricture/stenosis (17%) were frequently associated risk factors for epididymo
      orchitis. In 73% of patients epididymo-orchitis recurred with exclusive
      antibiotic treatment. Diverting colostomy was ineffective in preventing epididymo
      orchitis. Division of rectourinary fistula was curative in 36% of patients, while
      in 34% epididymo-orchitis recurred even after division of rectourinary fistula.
      Division of rectourinary fistula is likely to resolve epididymo-orchitis in the
      absence of additional risk factors. Vasectomy was required in 22% of patients to
      prevent recurrence. CONCLUSIONS: In addition to rectourinary fistula, urinary
      reflux into the vas deferens and neurovesical dysfunction are major risk factors
      for epididymo-orchitis in anorectal malformation. Division of rectourinary
      fistula is curative in only a third of cases. In the remaining cases some form of
      surgical disruption of the vas deferens is needed to resolve recurrent epididymo
      orchitis.

PMID- 21862042
TI  - Editorial comment.

PMID- 21862043
TI  - Editorial comment.

PMID- 21862044
TI  - Re: Identification of high risk pathological node positive penile carcinoma:
      value of preoperative computerized tomography imaging. N. M. Graafland, H. J.
      Teertstra, A. P. E. Besnard, H. H. Van Boven and S. Horenblas. J Urol 2011; 185:
      881-887.

PMID- 21862045
TI  - Clinical evolution of vesicoureteral reflux following endoscopic puncture in
      children with duplex system ureteroceles.
AB  - PURPOSE: We studied the clinical evolution of vesicoureteral reflux after
      endoscopic puncture of ureterocele in pediatric duplex systems. MATERIALS AND
      METHODS: We retrospectively reviewed charts of children with duplex system
      ureteroceles treated between 1992 and 2007. We analyzed patient age, prenatal
      diagnosis, urinary tract infection at presentation, differential renal function
      and preoperative vesicoureteral reflux. The fate of associated vesicoureteral
      reflux after endoscopic puncture of ureterocele was specifically addressed.
      RESULTS: We analyzed 60 patients with a mean age of 12 months, of whom 32 (52%)
      were diagnosed prenatally and 40 (66%) presented with a urinary tract infection.
      The majority of ureteroceles were ectopic, and pre-puncture vesicoureteral reflux
      was seen in 40 patients (67%). Postoperative voiding cystourethrogram was
      performed in 50 cases. New onset of vesicoureteral reflux occurred
      postoperatively in 24 patients (40%), mainly ipsilateral to the lower pole or
      contralaterally. Spontaneous vesicoureteral reflux resolution or improvement
      occurred in 16 of 22 patients (72%) observed after primary endoscopic puncture of
      ureterocele. Surgical intervention after endoscopic puncture of ureterocele was
      performed in 25 patients (42%), of whom 9 underwent more than 1 reparative
      procedure. CONCLUSIONS: Vesicoureteral reflux after endoscopic puncture of
      ureterocele may occur in the ipsilateral upper or lower poles, or in the
      contralateral renal segments. Therefore, the reflux is not necessarily related to
      the puncture itself. Vesicoureteral reflux after endoscopic puncture of
      ureterocele can resolve spontaneously in a significant number of patients.
      Therefore, initial management by close surveillance is warranted. Considering the
      simplicity of the procedure, our findings support that endoscopic puncture of
      ureterocele is an attractive alternative for the initial management of pediatric
      duplex system ureteroceles.

PMID- 21862046
TI  - Radiation exposure during pediatric videourodynamics.
AB  - PURPOSE: Videourodynamics is useful for evaluating and treating neurological
      disorders in children. Traditional urodynamic parameters can be obtained while
      simultaneous visualization of the urinary system can reveal anatomical anomalies.
      This additional information comes at the cost of radiation exposure to the child.
      We characterized radiation exposure from videourodynamics. MATERIALS AND METHODS:
      We reviewed all recent videourodynamic studies and recorded patient demographics,
      urological diagnoses, physical attributes, total fluoroscopy time, total
      radiation exposure in mGy, bladder capacity and the number of filling cycles
      performed. Multivariate linear regression was used to identify patient factors
      that independently influenced total radiation exposure. RESULTS: A total of 64
      videourodynamic studies were performed in 34 female and 28 male patients with a
      mean age of 8.6 years (95% CI 7.2-10.0). The most common diagnosis was neurogenic
      bladder in 40 patients, although 49 had multiple diagnoses. Mean total
      fluoroscopy time was 1.8 minutes (95% CI 1.4-2.1) and mean total radiation
      exposure was 10 mGy (95% CI 7.5-13.3). On multivariate linear regression patient
      weight and bladder capacity were the only independent predictors of total
      radiation exposure. CONCLUSIONS: Videourodynamics entail significant radiation
      exposure. Patient weight and bladder capacity were independent predictors of
      total radiation exposure. Physician awareness of radiation exposure may result in
      the judicious use of fluoroscopy and aid in counseling parents on the risk of
      videourodynamics. Further research is needed to quantify organ specific doses of
      radiation due to medical imaging in children and the associated cancer risks.

PMID- 21862047
TI  - Editorial comment.

PMID- 21862048
TI  - Editorial comment.

PMID- 21862049
TI  - Nephrogenic adenoma in the augmented bladder.
AB  - PURPOSE: Nephrogenic adenoma is an uncommon, benign urothelial lesion. Risk
      factors for nephrogenic adenoma include trauma, chronic inflammation,
      immunosuppression and radiation. We characterized nephrogenic adenoma in the
      pediatric augmented bladder. MATERIALS AND METHODS: We reviewed the records of
      patients diagnosed with nephrogenic adenoma from January 2000 to March 2010.
      Those with prior bladder augmentation were studied further. Data were
      retrospectively obtained on pathological characteristics, cystoscopic findings,
      recurrence patterns and presentation. RESULTS: Ten patients with ileal bladder
      augmentation and nephrogenic adenoma were identified. The underlying pathological
      condition was myelodysplasia in 7 patients, sacral agenesis in 2 and bladder
      exstrophy in 1. Concomitant procedures were a continent channel in 9 patients,
      ureteroneocystostomy in 5 and bladder neck reconstruction in 7. Mean time to the
      discovery of nephrogenic adenoma was 9.2 years. During that time a total of 221
      surveillance cystoscopies were performed in patients with bladder augmentation.
      The diagnosis was made by surveillance cystoscopy in 7 cases, at surgery for
      bladder stone in 2 and by cystoscopy for urinary incontinence in 1. Nephrogenic
      adenoma was identified along the floor in 5 cases, near the channel entrance in 3
      and adjacent to the enteric anastomosis in 2. Six patients returned for
      surveillance with recurrence identified in 2. The longest recurrence free
      interval was 27 months. CONCLUSIONS: Nephrogenic adenoma is not uncommon in the
      augmented bladder and it is often asymptomatic. The lesions tend to develop at
      sites that may be prone to chronic catheterization injury. Recurrent lesions are
      not unusual.

PMID- 21862050
TI  - Editorial comment.

PMID- 21862051
TI  - Editorial comment.

PMID- 21862052
TI  - Editorial comment.

PMID- 21862054
TI  - Editorial comment.

PMID- 21862056
TI  - Re: Glanuloplasty with urethral flap after partial penectomy. J. J. Belinky, G.
      M. Cheliz, C. A. Graziano and H. M. Rey. J Urol 2011; 185: 204-206.

PMID- 21862057
TI  - Editorial comment.

PMID- 21862058
TI  - Editorial comment.

PMID- 21862059
TI  - Gender assignment for newborns with 46XY cloacal exstrophy: a 6-year followup
      survey of pediatric urologists.
AB  - PURPOSE: Gender assignment for newborns with ambiguous genitalia remains a
      challenge. An initial survey of colleagues on this subject was performed in 2004.
      Our objective was to understand the basis for the attitudes and practices of
      pediatric urologists in regard to gender assignment for 46XY cloacal exstrophy in
      a 6-year followup survey. MATERIALS AND METHODS: A survey on a case of 46XY
      cloacal exstrophy was completed by 191 of the 263 fellows (73%) in the Urology
      Section, American Academy of Pediatrics. Questions referred to gender assignment,
      surgery timing, clinical outcomes and respondent demographics. RESULTS: Of the
      fellows 79% favored male gender assignment. The most important factor in male
      assignment remained androgen brain imprinting (97%) while in female assignment it
      was surgical success in creating functional genitalia (96%). Respondent
      characteristics associated with assigning female gender were longer practice
      duration (greater than 15 years) (p <0.03), having trained in programs where
      female gender was always or usually assigned (p <0.02) and not being a fellowship
      program director (0 of 27 respondents, p <0.03). There was an evolution among
      respondents from female gender assignment earlier in the career to male
      assignment currently (p <0.0001). CONCLUSIONS: Most pediatric urologists favor
      male gender assignment for 46XY cloacal exstrophy, which is a significant
      increase in 6 years. This change represents an evolution from female to male
      gender assignment and virtual unanimity among fellowship directors to gender
      assign male. Longer practicing clinicians perceived better outcomes for female
      gender assignment. If this reflects true clinical outcomes, the trend toward the
      eventual disappearance of female gender assignment for 46XY cloacal exstrophy is
      concerning.

PMID- 21862060
TI  - Testicular symmetry and adolescent varicocele--does it need followup?
AB  - PURPOSE: Appropriate management for adolescent varicocele with testicular
      symmetry is rarely discussed. We examined the natural history of varicocele in
      patients presenting with testicular symmetry to achieve better understanding of
      the clinical course. MATERIALS AND METHODS: Our varicocele registry was queried
      for adolescent boys who presented with varicocele in association with less than
      15% testicular asymmetry and who underwent at least 1 testicular asymmetry
      assessment 12 or more months later. Patients were stratified into 2 groups based
      on an initial testicular asymmetry measurement of less than 10% vs 10.0% to
      14.9%. Logistic regression modeling was used to analyze the association of Tanner
      stage, varicocele grade, peak retrograde flow and maximum vein diameter at
      presentation with increased testicular asymmetry at followup. Kaplan-Meier
      methodology was applied to compare testicular asymmetry progression rates.
      RESULTS: We identified 89 adolescents, of whom 52 (58.4%) and 37 (41.6%)
      presented with less than 10.0% and 10.0% to 14.9% testicular asymmetry,
      respectively. Of the patients 37 (41.6%) showed testicular asymmetry progression
      at a median 18-month followup. The overall 3-year testicular asymmetry
      progression-free rate was 48% while in patients with peak retrograde flow 30 cm
      per second or greater it was 23%. On multivariate analysis controlled for age,
      Tanner stage and varicocele grade a peak retrograde flow of 30 cm per second or
      greater was associated with worsening testicular asymmetry (OR 4.87, 95% CI 1.6
      8.0). CONCLUSIONS: Adolescents with varicocele and less than 15% testicular
      asymmetry are at risk for asymmetry during followup. Those with peak retrograde
      flow 30 cm per second or greater are at increased risk for early asymmetry while
      those with peak retrograde flow less than 30 cm per second may still show
      asymmetry but tend to do so after longer followup.

PMID- 21862062
TI  - Editorial comment.

PMID- 21862063
TI  - Comparison of endoscopic ureterocele decompression techniques. Preliminary
      experience--is the watering can puncture superior?
AB  - PURPOSE: The optimal endoscopic technique to manage an obstructing ureterocele
      would reliably relieve obstruction without creating de novo vesicoureteral
      reflux. The classic incision achieves decompression but invariably creates new
      vesicoureteral reflux. We compared a new endoscopic puncture technique to assess
      its superiority to endoscopic incision. MATERIALS AND METHODS: We retrospectively
      reviewed 27 consecutive endoscopic ureterocele procedures at our institution.
      Patients who underwent an endoscopic incision or watering can puncture procedure
      had their records reviewed for preoperative radiological and clinical data,
      operative description, and postoperative radiological and clinical outcomes.
      RESULTS: Of the 15 patients with endoscopic ureterocele incision 11 underwent a
      watering can puncture. All ureteroceles were associated with grade 3 or 4
      hydronephrosis. Incision successfully decompressed the ureterocele in 14 of 16
      cases (87.5%) and hydronephrosis in 14 (87.5%) on postoperative renal ultrasound.
      De novo reflux was detected in 12 of 16 patients (75.0%) on postoperative voiding
      cystourethrogram. Puncture successfully decompressed the ureterocele in 10 of 11
      cases (90.9%) and hydronephrosis in 9 (81.8%). De novo vesicoureteral reflux was
      detected in 4 of 11 patients (36.4%). CONCLUSIONS: Our initial review shows that
      the endoscopic watering can procedure successfully decompresses the obstructing
      ureterocele and its associated hydronephrosis. This technique also results in a
      decreased incidence of de novo vesicoureteral reflux and ultimately in fewer
      invasive procedures for the patient.

PMID- 21862064
TI  - Editorial comment.

PMID- 21862065
TI  - Comparative histological and functional controlled analysis of tubularized
      incised plate urethroplasty with and without dorsal inlay graft: a preliminary
      experimental study in rabbits.
AB  - PURPOSE: We analyzed the histological and functional characteristics of the
      tubularized incised plate vs dorsal inlay graft urethroplasty in an experimental
      rabbit model. MATERIALS AND METHODS: A total of 24 New Zealand male rabbits were
      randomly allocated into 4 groups, including sham operation, urethroplasty,
      tubularized incised plate urethroplasty and dorsal inlay graft urethroplasty. In
      the urethroplasty group the anterior urethral wall was half excised and the
      dorsal aspect was tubularized. In the tubularized incised plate group the same
      steps were followed but tubularization followed a longitudinal midline incision
      in the dorsal wall. In the dorsal inlay graft group the defect created by the
      dorsal incision was covered with an inner preputial graft. The animals were
      sacrificed at 4 and 8 weeks, respectively. The penis was immediately harvested
      for standardized passive flowmetry and subsequently fixed for histological
      staining. RESULTS: The grafts took in all animals. The tubularized incised plate
      defect was bridged by urothelium while in the dorsal inlay graft group the
      preputial graft kept its original histological characteristics. There was a
      significant decrease in average flow in the urethroplasty group (1.6 ml per
      second) compared to that in the sham operated group (3.4 ml per second) and to
      the other groups (p <0.05). However, no significant difference in average flow
      was found for the tubularized incised plate and dorsal inlay graft groups (2.4
      and 2.2 ml per second, respectively, p = 0.7). CONCLUSIONS: In this short-term
      rabbit model dorsal inlay graft urethroplasty was feasible with good graft take
      and integration. Simple tubularization of a reduced urethral plate led to
      significantly decreased flow. Incision of the reduced plate with or without
      grafting improved the average flow. Findings in this experimental model do not
      support the superiority of dorsal inlay graft urethroplasty over tubularized
      incised plate urethroplasty in terms of urethral flow dynamics.

PMID- 21862067
TI  - High risk of sleep disordered breathing in the enuresis population.
AB  - PURPOSE: Enuresis is 1 of the most common complaints facing pediatric urologists
      and it has significant implications with respect to quality of life. Although the
      pathophysiology is incompletely understood, there is growing evidence that sleep
      disordered breathing in children, including obstructive sleep apnea, has a
      fundamental role. There are also potentially fundamental differences between
      monosymptomatic enuresis, which may be a sleep disorder, and nonmonosymptomatic
      enuresis, which may relate to a primary bladder storage problem. We prospectively
      evaluated the incidence of obstructive sleep apnea in patients with enuresis and
      analyzed differences between patients with monosymptomatic and nonmonosymptomatic
      enuresis. MATERIALS AND METHODS: A total of 69 children with enuresis were given
      3 validated questionnaires to complete, including the Dysfunctional Voiding and
      Incontinence Symptom Score, the Obstructive Sleep Apnea Quality of Life survey
      and the Modified Pediatric Sleep Questionnaire. The Dysfunctional Voiding and
      Incontinence Symptom Score quantifies patient dysfunctional voiding habits. The
      Obstructive Sleep Apnea Quality of Life survey evaluates patient quality of life
      in regard to obstructive sleep apnea and its effects. Modified Pediatric Sleep
      Questionnaire results describe the severity of patient sleep disturbances.
      RESULTS: The mean Obstructive Sleep Apnea Quality of Life Survey score was 43 and
      54% of patients had positive Modified Pediatric Sleep Questionnaire results,
      indicating that obstructive sleep apnea was prevalent in our population. Those
      with enuresis and daytime incontinence were significantly more likely to have
      sleep disordered breathing than those with monosymptomatic enuresis (p <0.05).
      CONCLUSIONS: Our study confirms the link between sleep disordered breathing and
      enuresis. All pediatric health care providers should be aware of this risk. The
      risk may be magnified in patients with concomitant daytime incontinence.

PMID- 21862068
TI  - Editorial comment.

PMID- 21862069
TI  - Editorial comment.

PMID- 21862070
TI  - How much does the midline incision add to urethral diameter after tubularized
      incised plate urethroplasty? An experimental animal study.
AB  - PURPOSE: We objectively quantified the gain in urethral diameter and the effect
      of stenting after tubularized incised plate urethroplasty in a rabbit hypospadias
      model. MATERIALS AND METHODS: We created a hypospadias model in 12 New Zealand
      white male rabbits by excising the ventral urethra. A 3 cm tattoo line was made
      longitudinally in the dorsal urethral plate midline. Two weeks later a 2 cm
      relaxing incision was made in the middle part of the tattooed line. The stretched
      incision width between the tattooed edges was measured, followed by urethral
      plate tubularization. Six rabbits were stented and 6 were nonstented. Two weeks
      later the animals were sacrificed and the distance separating the tattoo was
      measured at the midpoint of the tattooed line. Transverse sections at this point
      were examined histologically. RESULTS: All animals survived the procedures.
      Stents were removed at 7 days in 4 rabbits and fell out in 2 at 4 and 2 days,
      respectively. The mean +/- SD incision width of 5.5 +/- 1.6 mm (range 3 to 8) at
      tubularization became 2 +/- 0.5 mm (range 1 to 3) after healing (p <0.002). Mean
      width of the healed incision was 1.7 +/- 0.4 (range 1 to 2) vs 2.3 +/- 0.5 mm
      (range 1.5 to 3) in the nonstented and stented groups, respectively (p <0.06).
      Rabbits with a stenting duration of less than 7 days were excluded from the last
      analysis. Histologically all incisions healed completely with an intact
      epithelium. CONCLUSIONS: The initial width of the midline relaxing incision
      significantly decreased after complete epithelialization. The average gain in
      urethral width was only 2 mm. Stenting appeared to increase the width of the
      healed incisions but not in a statistically significant manner.

PMID- 21862071
TI  - Long-term outcome of excisional organ sparing surgery for carcinoma of the penis.
AB  - PURPOSE: We present our experience with penile sparing surgery for localized
      carcinoma in situ and T1 penile squamous cell carcinoma. We report outcomes and
      recommendations for a penile sparing approach. MATERIALS AND METHODS: A total of
      60 patients underwent penile sparing surgery for penile squamous cell carcinoma
      since 1995. Four patients without recurrence had less than 6 months of followup
      and were excluded from study. Data included disease stage, cellular
      differentiation, tumor site, penile sparing surgery type and recurrence
      information. RESULTS: Followup was adequate in 28 patients with carcinoma in situ
      and in 28 with T1 disease. The overall recurrence rate was 21.4% with equal
      recurrences of carcinoma in situ and T1 tumors (each 21.4%). Mean +/- SD time to
      recurrence was 4.28 +/- 2.81 years (range 0.5 to 11). More than 25% of
      recurrences developed after 5 years. Mean followup in censored patients was 5.47
      +/- 3.88 years (maximum 16). There was no difference in time to recurrence after
      carcinoma in situ and T1 tumors (p = 0.738). T1 tumors on the glans carried a
      slightly higher risk of recurrence (p = 0.049). At 5 years 13.8% of patients at
      risk had late recurrence with a mean time to recurrence of 7.25 +/- 2.62 years.
      No patients with carcinoma in situ showed invasion or metastasis. Two patients
      with T1 disease presented with metastasis and 3 had late metastasis. CONCLUSIONS:
      Penile sparing surgery is a safe option for local control for appropriate
      carcinoma in situ and T1 squamous cell carcinoma of the penis. Carcinoma in situ
      recurrence may be re-treated with penile sparing surgery. T1 tumors that recur
      require more aggressive resection. Our data show significant late recurrences in
      patients and the need for long-term followup.

PMID- 21862072
TI  - Gleason score 7 prostate cancer on needle biopsy: relation of primary pattern 3
      or 4 to pathological stage and progression after radical prostatectomy.
AB  - PURPOSE: There have been only a few contradictory publications assessing whether
      Gleason score 4 + 3 = 7 has a worse prognosis than 3 + 4 = 7 on biopsy material
      in predicting pathological stage and biochemical recurrence. Older studies
      predated the use of the modified Gleason grading system established in 2005.
      MATERIALS AND METHODS: We retrospectively studied 1,791 cases of Gleason score 7
      on prostatic biopsy to determine whether the breakdown of Gleason score 7 into 3
      + 4 vs 4 + 3 has prognostic significance in the modern era. RESULTS: There was no
      difference in patient age, preoperative serum prostate specific antigen, maximum
      tumor percent per core or the number of positive cores between Gleason score 3 +
      4 = 7 and Gleason score 4 + 3 = 7. Gleason score 4 + 3 = 7 showed an overall
      correlation with pathological stage (organ confined, focal extraprostatic
      extension, nonfocal extraprostatic extension, seminal vesicle invasion/lymph node
      metastases, p = 0.005). On multivariate analysis Gleason score 4 + 3 = 7 (p =
      0.03), number of positive cores (p = 0.002), maximum percent of cancer per core
      (p = 0.006) and preoperative serum prostate specific antigen (p = 0.03) all
      correlated with pathological stage. Gleason score 4 + 3 = 7 on biopsy was also
      associated with an increased risk of biochemical progression after radical
      prostatectomy (p = 0.0001). On multivariate analysis Gleason score 4 + 3 = 7 (p =
      0.001), maximum percent of cancer per core (p <0.0001) and preoperative serum
      prostate specific antigen (p <0.0001) but not number of positive cores correlated
      with the risk of biochemical progression after radical prostatectomy.
      CONCLUSIONS: Our study further demonstrates that Gleason score 7 should not be
      considered a homogenous group for the purposes of disease management and
      prognosis.

PMID- 21862073
TI  - Results: Survey of pediatric urology electronic medical records-use and
      perspectives.
AB  - PURPOSE: The $19.2 billion Health Information Technology for Economic and
      Clinical Health Act will have a dramatic effect on the adoption of electronic
      medical records in the United States by directly reimbursing for the adoption of
      electronic medical records in the future. We sought to gain an understanding of
      electronic medical record use in pediatric urology to aid in the transition to
      electronic medical records. MATERIALS AND METHODS: All Fellows and post
      fellowship Fellow Candidates of the American Academy of Pediatrics Section on
      Urology were recruited to participate in the survey. Electronic and paper
      versions of this 50-question internal review board approved anonymous survey were
      sent to potential participants. RESULTS: Of 286 pediatric urologists 165
      completed the survey for a 65% response rate. Of the respondents 67.3% were
      pediatric urologists in academic or hospital based practice while the remaining
      32.7% were in private practice. Overall 78.8% of respondents reported using
      electronic medical records at the hospital while 67.3% used them at the
      office/clinic. Of the physicians 12.1% reported that they would retire if
      electronic medical record use was federally mandated. CONCLUSIONS: Pediatric
      urologists in the United States appear to have embraced the adoption of
      electronic medical records. A large number of academic/hospital based and private
      practice pediatric urologists have begun to use electronic medical records. Most
      respondents were interested in improving electronic medical record use in our
      field, believed that physicians would be most capable of developing ideal
      electronic medical records and would be interested in participating in a national
      cooperative effort to improve electronic medical record use.

PMID- 21862074
TI  - The impact of surgical approach and urinary diversion on patient outcomes in
      pediatric pyeloplasty.
AB  - PURPOSE: Recent comparisons of the impact of the surgical approach on pediatric
      pyeloplasty outcomes have generally incorporated a form of internal ureteral
      drainage. We hypothesized that the surgical approach does not affect outcomes in
      children who undergo unstented pyeloplasty and stenting offers no long-term
      benefit in those with pediatric pyeloplasty. MATERIALS AND METHODS: After
      receiving institutional review board approval we examined the records of all
      children who underwent initial pyeloplasty from December 2001 to December 2009.
      We compared unstented and stented pyeloplasties, and each surgical approach in
      the unstented group. RESULTS: During the study period 367 pyeloplasties were
      performed, including 231 unstented and 136 stented procedures. When comparing
      unstented to stented pyeloplasties, there was no difference in the complication
      or failure rate. Of unstented pyeloplasties 71, 67 and 93 were done using a
      transperitoneal laparoscopic approach, a flank approach and dorsal lumbotomy,
      respectively. There were 5 failures, of which 2 were laparoscopic, 2 used a flank
      approach and 1 used dorsal lumbotomy (p = 0.51). A total of 31 patients,
      including 10 treated with a laparoscopic approach, 3 with a flank approach and 18
      with dorsal lumbotomy (p = 0.02), required second procedures, of which 24 were
      temporary drainage for a urine leak. Univariate analysis of factors associated
      with secondary procedures in the unstented pyeloplasty group showed that only
      surgical approach was significant (p = 0.05). CONCLUSIONS: In pediatric
      pyeloplasty there is no significant difference in outcome between stented and
      unstented repairs. In unstented repairs complications may vary by surgical
      approach. Regardless of the approach unstented pyeloplasty is safe and effective
      in the pediatric population.

PMID- 21862076
TI  - Editorial comment.

PMID- 21862077
TI  - Editorial comment.

PMID- 21862078
TI  - Editorial comment.

PMID- 21862079
TI  - Human capital gains associated with robotic assisted laparoscopic pyeloplasty in
      children compared to open pyeloplasty.
AB  - PURPOSE: Robotic assisted laparoscopic pyeloplasty is an emerging, minimally
      invasive alternative to open pyeloplasty in children for ureteropelvic junction
      obstruction. The procedure is associated with smaller incisions and shorter
      hospital stays. To our knowledge previous outcome analyses have not included
      human capital calculations, especially regarding loss of parental workdays. We
      compared perioperative factors in patients who underwent robotic assisted
      laparoscopic and open pyeloplasty at a single institution, especially in regard
      to human capital changes, in an institutional cost analysis. MATERIALS AND
      METHODS: A total of 44 patients 2 years old or older from a single institution
      underwent robotic assisted (37) or open (7) pyeloplasty from 2008 to 2010. We
      retrospectively reviewed the charts to collect demographic and perioperative
      data. The human capital approach was used to calculate parental productivity
      losses. RESULTS: Patients who underwent robotic assisted laparoscopic pyeloplasty
      had a significantly shorter average hospital length of stay (1.6 vs 2.8 days, p
      <0.05). This correlated with an average savings of lost parental wages of $90.01
      and hospitalization expenses of $612.80 per patient when excluding amortized
      robot costs. However, cost savings were not achieved by varying length of stay
      when amortized costs were included. CONCLUSIONS: Robotic assisted laparoscopic
      pyeloplasty in children is associated with human capital gains, eg decreased lost
      parental wages, and lower hospitalization expenses. Future comparative outcome
      analyses in children should include financial factors such as human capital loss,
      which can be especially important for families with young children.

PMID- 21862080
TI  - Long-term urological impact of fetal myelomeningocele closure.
AB  - PURPOSE: Between 1997 and 2002 a large number of fetal myelomeningocele closures
      were performed at our institution. Previously early reports showed little
      improvement in neonatal bladder function after fetal back closure. We evaluated
      the long-term urological impact of this procedure. MATERIALS AND METHODS: Using a
      combination of retrospective review and survey questionnaire we reviewed the
      records of 28 patients in whom fetal myelomeningocele closure was done at our
      institution between 1997 and 2002. The areas addressed included medical
      management for neurogenic bladder and bowel, need for lower urinary tract
      reconstruction and functional bladder assessment by videourodynamics. Parameters
      after fetal myelomeningocele closure were compared to those of 33 age and sex
      matched patients with myelomeningocele who underwent standard postnatal closure.
      RESULTS: We reviewed the records of 28 patients after fetal myelomeningocele
      closure. At a mean age of 9.6 years 23 used clean intermittent catheterization to
      manage the bladder, 24 required a bowel regimen to manage constipation and 6
      underwent lower urinary tract reconstruction with enterocystoplasty and a
      catheterizable bladder channel. Videourodynamics performed in 14 patients at a
      mean age of 7.4 years revealed decreased bladder capacity in 71%, detrusor
      overactivity in 35% and increased detrusor pressure in 25%. Compared to age and
      sex matched children who underwent postnatal closure we noted no significant
      differences in bladder management, urinary tract surgery or urodynamics.
      CONCLUSIONS: Neurogenic bowel and bladder management continues to be a
      significant issue for patients after fetal myelomeningocele closure. After fetal
      surgery patients should be followed closely, similar to patients who undergo
      postnatal closure.

PMID- 21862081
TI  - Editorial comment.

PMID- 21862083
TI  - Simplifying the diagnosis of 4 common voiding conditions using
      uroflow/electromyography, electromyography lag time and voiding history.
AB  - PURPOSE: Noninvasive uroflowmetry with simultaneous electromyography is useful to
      triage cases of lower urinary tract symptoms into 4 urodynamically defined
      conditions, especially when incorporating short and long electromyography lag
      times in the analysis. We determined the prevalence of these 4 conditions at a
      single referral institution and the usefulness of uroflowmetry with simultaneous
      electromyography and electromyography lag time to confirm the diagnosis, guide
      treatment and monitor response. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 100 consecutive normal children who presented with
      persistent lower urinary tract symptoms, underwent uroflowmetry with
      electromyography as part of the initial evaluation and were diagnosed with 1 of 4
      conditions based on certain uroflowmetry/electromyography features. The
      conditions included 1) dysfunctional voiding--active pelvic floor
      electromyography during voiding with or without staccato flow, 2a) idiopathic
      detrusor overactivity disorder-A--a quiet pelvic floor during voiding and
      shortened lag time (less than 2 seconds), 2b) idiopathic detrusor overactivity
      disorder-B--a quiet pelvic floor with a normal lag time, 3) detrusor
      underutilization disorder--volitionally deferred voiding with expanded bladder
      capacity but a quiet pelvic floor, and 4) primary bladder neck dysfunction-
      prolonged lag time (greater than 6 seconds) and a depressed, right shifted
      uroflowmetry curve with a quiet pelvic floor during voiding. Treatment was
      tailored to the underlying condition in each patient. RESULTS: The group
      consisted of 50 males and 50 females with a mean age of 8 years (range 3 to 18).
      Dysfunctional voiding was more common in females (p <0.05) while idiopathic
      detrusor overactivity disorder-B and primary bladder neck dysfunction were more
      common in males (p <0.01). With treatment uroflowmetry parameters normalized for
      all types. Electromyography lag time increased in idiopathic detrusor
      overactivity disorder-A cases and decreased in primary bladder neck dysfunction
      cases. CONCLUSIONS: Noninvasive uroflowmetry with simultaneous electromyography
      offers an excellent alternative to invasive urodynamics to diagnose 4
      urodynamically defined conditions. It identifies the most appropriate therapy for
      the specific condition and objectively monitors the treatment response.

PMID- 21862084
TI  - Editorial comment.

PMID- 21862085
TI  - Editorial comment.

PMID- 21862086
TI  - Sources of hepatic glycogen synthesis following a milk-containing breakfast meal
      in healthy subjects.
AB  - During feeding, dietary galactose is a potential source of hepatic glycogen
      synthesis; but its contribution has not been measured to date. In the presence of
      deuterated water ((2)H(2)O), uridine diphosphate (UDP)-glucose derived from
      galactose is not enriched, whereas the remainder derived from glucose-6-phosphate
      (G6P) is enriched in position 2 to the same level as body water, assuming
      complete G6P-fructose-6-phosphate (F6P) exchange. Hence, the difference between
      UDP-glucose position 2 and body water enrichments reflects the contribution of
      galactose to glycogen synthesis relative to all other sources. In study 1, G6P
      F6P exchange in 6 healthy subjects was quantified by supplementing a milk
      containing breakfast meal with 10 g of [U-(2)H(7)]glucose and quantifying the
      depletion of position 2 enrichment in urinary menthol glucuronide. In study 2,
      another 6 subjects ingested (2)H(2)O and acetaminophen followed by an identical
      breakfast meal with 10 g of [1-(13)C]glucose to resolve direct/indirect pathways
      and galactose contributions to glycogen synthesis. Metabolite enrichments were
      determined by (2)H and (13)C nuclear magnetic resonance. In study 1, G6P-F6P
      exchange approached completion; therefore, the difference between position 2 and
      body water enrichments in study 2 (0.20% +/- 0.03% vs 0.27% +/- 0.03%, P < .005)
      was attributed to galactose glycogenesis. Dietary galactose contributed 19% +/-
      3% to glycogen synthesis. Of the remainder, 58% +/- 5% was derived from the
      direct pathway and 22% +/- 4% via the indirect pathway. The contribution of
      galactose to hepatic glycogen synthesis was resolved from that of direct and
      indirect pathways using a combination of (2)H(2)O and [1-(13)C]glucose tracers.

PMID- 21862087
TI  - Mechanisms for the social gradient in health: results from a 14-year follow-up of
      the Northern Swedish Cohort.
AB  - OBJECTIVE: Although numerous studies have demonstrated a socio-economic gradient
      in health, there is still a lack of research about the mechanisms behind this
      gradient. The aim of this study was to analyse possible mechanisms from
      adolescence to adulthood to explain the socio-economic gradient in somatic
      symptoms among men and women in the Northern Swedish Cohort. STUDY DESIGN: A
      prospective cohort study was performed, in which all pupils (n = 1083) in the
      last year of compulsory school were followed for 14 years. The response rate was
      high, with 96.6% still participating after 14 years. The data were mainly
      collected through repeated comprehensive self-administered questionnaires.
      METHODS: The main dependent variable was a combination of socio-economic position
      and somatic health at 30 years of age. Multivariate multinomial and bivariate
      logistic regression analyses were undertaken. RESULTS: After controlling for
      parental working-class position and health-related selection, the authors
      identified mechanisms from adolescence to adulthood for the socio-economic
      gradient in health that were related to social relations (poor relationship with
      father and unemployed friends among men, violence among women), labour market
      experiences (unemployment among men and women, physically heavy work among
      women), economic hardship (among women) and poor health behaviour. CONCLUSION:
      These analyses contribute to the development of epidemiological methods for
      analysing mechanisms for the socio-economic gradient in health.

PMID- 21862088
TI  - Effects of Solanum glaucophyllum toxicity on cell proliferation and apoptosis in
      the small and large intestine of rabbits.
AB  - Vitamin D regulates mineral homeostases and enterocyte proliferation and
      differentiation. Hypervitaminosis D generates changes in cell proliferation,
      differentiation and apoptosis in several organs. We analysed morphometric
      parameters and proliferative and apoptotic indices in the intestinal epithelium
      of rabbits with hypervitaminosis D induced by the chronic treatment with the
      calcinogenic plant Solanum glaucophyllum. Rabbits were treated for 15 or 30 days.
      A group was treated for 15 days and led to possible recovery for 30 days. Another
      group was nutritionally restricted for 30 days. Morphological, morphometric,
      proliferative and apoptotic changes were found in the treated animals. Mild
      atrophy and reduced proliferation was found in the jejunum and ileum. Apoptosis
      increased in the crypts of the ileum and in the superficial epithelium and crypts
      of the rectum. Most of the alterations were partially recovered. The possible
      involvement in these changes of the hypervitaminosis D-like state induced by S.
      glaucophyllum is discussed.

PMID- 21862089
TI  - Identification and phenotypic characterization of gammadelta T cells in rat
      lymph.
AB  - gammadelta T cells represent an unconventional subset of T lymphocytes that are
      abundant in epithelial tissues and serve as an early immune defense against
      microbes. We have, for the first time, identified gammadelta T cells in steady
      state thoracic duct lymph (TDL) from rats. The lymph contains gammadelta T cells
      expressing CD8 but not CD4, CD25, MHC-II or CD103. The percentage of TDL
      gammadelta T cells in rats does not change when the mesenteric lymph nodes (MLN)
      are surgically removed. Our data suggest that a proportion of gammadelta T cells
      migrate from the intestine into rat TDL, under steady-state conditions.

PMID- 21862090
TI  - Effects of supplemental recombinant bovine somatotropin and mist-fan cooling on
      the renal tubular handling of sodium in different stages of lactation in
      crossbred Holstein cattle.
AB  - The effect of supplementary administration of recombinant bovine somatotrophin
      (rbST) on the renal tubular handling of sodium in crossbred 87.5% Holstein cattle
      housed in normal shade (NS) or mist-fan cooled (MF) barns was evaluated. The cows
      were injected with 500 mg rbST at three different stages of lactation. The MF
      barn housed cows showed a slightly decreased ambient temperature and temperature
      humidity index, but an increased relative humidity. Rectal temperature and
      respiration rates were significantly lower in cooled cows. The rbST treated cows,
      housed in NS or MF barns, showed markedly increased milk yields, total body
      water, extracellular fluid and plasma volume levels, along with a reduced rate of
      urine flow and urinary excretion of sodium, potassium and chloride ions and
      osmolar clearance, in all three stages of lactation. Renal tubular sodium and
      water reabsorption were increased after rbST administration without any
      alteration in the renal hemodynamics. Lithium clearance data suggested that the
      site of response is in the proximal nephron segment, which may be mediated via
      increases in the plasma levels of aldosterone and IGF-1, but not vasopressin,
      during rbST administration.

PMID- 21862091
TI  - Serological screening for Coxiella burnetii infection and related reproductive
      performance in high producing dairy cows.
AB  - The possible relationship between Coxiella-seropositivity and the reproductive
      performance of cows during the previous year to the serological screening was
      examined in three high producing dairy herds. The herds had a history of
      subfertility (<25% of pregnancies for the total number of AI), abortion (>18%
      abortions) and a positive polymerase chain reaction test for Coxiella burnetii in
      the bulk tank milk with an excretion higher than 10(4)Coxiella /ml for all three
      herds. Antibodies against C. burnetii were detected in 50.2% of the 781 parous
      cows analyzed. Coxiella seropositivity was linked to placenta retention, to
      changes in the interval from parturition to conception (with the lowest interval
      parturition-conception for cows with low level of seropositivity), early
      pregnancy (cows becoming pregnant before Day 90 postpartum) and maintenance of
      gestation during the early fetal period, while it failed to affect rates of
      abortion after Day 90 of gestation or stillbirth.

PMID- 21862092
TI  - Molecular detection of Streptococcus agalactiae in bovine raw milk samples
      obtained directly from bulk tanks.
AB  - Mastitis is the most common infectious disease affecting dairy cattle; in
      addition, it remains the most economically important disease of dairy industries
      around the world. Streptococcus agalactiae, a contagious pathogen associated with
      subclinical mastitis, is highly infectious. This bacterium can cause an increase
      in bulk tank bacterial counts (BTBC) and bulk tank somatic cell counts (BTSCC).
      The microbiological identification of S. agalactiae in samples from bulk tanks is
      an auxiliary method to control contagious mastitis. Thus, there are some
      limitations for time-consuming cultures or identification methods and additional
      concerns about the conservation and transport of samples. Bulk tank samples from
      247 dairy farms were cultured and compared through polymerase chain reaction
      (PCR), directed to 16S rRNA genes of S. agalactiae, followed by BTBC and S.
      agalactiae isolation. The mean value of BTBC was 1.08*10(6) CFU mL(-1) and the
      bacterium was identified through the microbiological method in 98 (39.7%;
      CI(95%)=33.8-45.9%) and through PCR in 110 (44.5%; CI(95%)=38.5-50.8%) samples.
      Results indicated sensitivity of 0.8571+/-0.0353 (CI(95%)=0.7719-0.9196) and
      specificity of 0.8255+/-0.0311 (CI(95%)=0.7549-0.8827). The lack of significant
      difference between microbiological and molecular results (kappa=0.6686+/-0.0477
      and CI(95%)=0.5752-0.7620) indicated substantial agreement between the methods.
      This suggests that PCR can be used for bulk tank samples to detect contagious
      mastitis caused by S. agalactiae.

PMID- 21862093
TI  - Field evaluation of urine antigen detection for diagnosis of Taenia solium
      cysticercosis.
AB  - (Neuro)cysticercosis is an important zoonotic disease caused by infection with
      Taenia solium metacestode larvae. Existing immunodiagnostic techniques detect
      antibodies and circulating antigens (Ag) in serum and cerebrospinal fluid (CSF).
      Blood/CSF collection is an invasive procedure associated with blood-borne
      infections and is often not well accepted by communities. Detection of
      circulating Ag in urine has been suggested as an alternative, however this has
      been evaluated in clinical settings only. The aim of the present study was to
      evaluate the performance of a urine Ag-ELISA under field conditions. Paired serum
      and urine samples were obtained from participants in endemic areas of Ecuador
      (n=748) and Zambia (n=690) and were subjected to a monoclonal antibody-based Ag
      ELISA. Calculation of positive and negative agreement indices (AI) showed better
      agreement in the negative direction both for Ecuadorian and Zambian samples (AI
      of 93.1 and 86.8, respectively). Using a Bayesian approach to determine the test
      characteristics, similar sensitivities were obtained for serum and urine Ag
      detection, whereas a decreased specificity was determined for the urine Ag-ELISA
      with a lower specificity (78.6%) for Zambian samples than for Ecuadorian samples
      (88.4%). This study indicates a higher specificity for the serum test under field
      conditions and promotes further research to improve the urine test.

PMID- 21862094
TI  - Bradykinin potentiating factor isolated from Buthus occitanus venom has a
      protective effect against cadmium-induced rat liver and kidney damage.
AB  - Bradykinin and its related peptides are widely distributed in venomous animals,
      including scorpion. A peptide fraction isolated from the venom of the Egyptian
      scorpion Buthus occitanus was proved to have a bradykinin-potentiating activity.
      The aim of the present study was conducted to investigate whether the treatment
      with bradykinin potentiating factor (BPF) offers more beneficial effects in
      reversing cadmium-induced oxidative stress in rat liver and kidney. Adult male
      rats, equally divided into control and two treated groups, 10 animals in each
      group. group (I) was orally given (1 ml) saline and served as a control group;
      group (II) of rats was given cadmium chloride (4 mg/kg) alone, once daily an oral
      dose for 7 successive days; group (III) of rats was given ip injection (1 ml)
      BPF, once daily a dose for 7 successive days prior to CdCl(2) treatment and on
      the next 7 successive days with the same dose of cadmium as group II. Both organs
      were subjected to histopathological analysis with the light microscope. The
      activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and
      alkaline phosphatase (ALP) in serum were measured as indicators of the liver
      function. As parameters of the kidney function, creatinine, uric acid and urea
      concentrations in serum were determined. Also, malondialdehyde (MDA), reduced
      glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined
      in both tissues. Cd exposure caused a significant decrease or inhibition in the
      activities of GSH, SOD, and CAT, with significant increase in the level of MDA,
      in versus to control groups in both liver and kidney. Also, when Cd was treated
      in co-administration with BPF induced increase or stimulation in the activity of
      GSH, SOD, and CAT, with significant decrease in the level of MDA when compared to
      Cd group in both organs. Histopathological changes of liver and kidney were also
      in accordance with the biochemical findings. Our data showed that Cd treatment
      induced histopathological alteration in the liver, severe hydropic degeneration
      in centrolobular zones. Inflammatory cells infiltration around the congested
      central vein and an obvious injury in some renal tubules. Bradykinin potentiating
      factor (BPF) administration prevented the histopathological alterations which
      observed in Cd-groups and both liver and kidney had essentially normal appearance
      in histopathological examination. In conclusion, BPF markedly ameliorated cadmium
      induced liver and kidney tissue damage as evidenced by histological and
      biochemical examinations and acts as a potent scavenger of free radicals to
      protect the liver and kidney against the deleterious effect of acute cadmium
      intoxication.

PMID- 21862095
TI  - Evolution of a helper virus-derived, ribosome binding translational enhancer in
      an untranslated satellite RNA of Turnip crinkle virus.
AB  - SatC is a noncoding subviral RNA associated with Turnip crinkle virus (TCV). A
      100-nt stretch in the 3' UTR of TCV contains three hairpins and two pseudoknots
      that fold into a tRNA-shaped structure (TSS) that binds 80S ribosomes. The 3'
      half of satC is derived from TCV and contains 6-nt differences in the TSS
      analogous region. SatC binds poorly to 80S ribosomes, and molecular modeling that
      predicted the 3D structure of the TSS did not predict a similar structure for
      satC. When the satC TSS region was step-wise converted to the original TCV TSS
      bases, ribosome binding increased to TCV TSS levels without significantly
      affecting satC replication. However, mutant satC was less fit when accumulating
      in plants and gave rise to numerous second site changes that weakened one of two
      satC conformations. These results suggest that minor changes from the original
      TCV sequence in satC reflect requirements other than elimination of ribosome
      binding.

PMID- 21862096
TI  - Protein fouling behavior of carbon nanotube/polyethersulfone composite membranes
      during water filtration.
AB  - The protein fouling of membranes can be related to the hydrophobic and
      electrostatic interactions between proteins and the membrane material; i.e.,
      protein fouling can be reduced by changing the membrane properties. In this
      study, multi-walled carbon nanotube/polyethersulfone (C/P) composite membranes
      were prepared via the phase inversion method in order to investigate protein
      fouling, with bovine serum albumin (BSA) and ovalbumin (OVA) used as the model
      protein for assessing the protein fouling behavior. The results show that the C/P
      composite membranes were fouled less compared to the bare polyethersulfone (PES)
      membrane at 4 h of static protein adsorption at neutral pH. Moreover, the
      irreversible fouling ratio of the C/P composite membranes was less than the bare
      PES membrane after 1 h of protein ultrafiltration, and the flux recovery ratio of
      the C/P composite membranes was higher than the bare PES membrane after 20 min of
      DI water filtration. Based on these results, C/P composite membranes were shown
      to have the potential to alleviate the effects of protein fouling, thereby
      enabling C/P composite membranes to be used for several runs of protein
      filtration after simple washing with water.

PMID- 21862097
TI  - Improving the efficiencies of simultaneous organic substance and nitrogen removal
      in a multi-stage loop membrane bioreactor-based PWWTP using an on-line Knowledge
      Based Expert System.
AB  - The results of the use of an expert system (ES) to control a novel multi-stage
      loop membrane bioreactor (MLMBR) for the simultaneous removal of organic
      substances and nutrients are reported. The study was conducted at a bench-scale
      plant for the purpose of meeting new discharge standards (GB21904-2008) for the
      treatment of chemical synthesis-based pharmaceutical wastewater (1200-9600 mg/L
      COD, 500-2500 mg/L BOD5, 50-200 mg/L NH4+-N and 105-400 mg/L TN in the influent
      water) by developing a distributed control system. The system allows various
      expert operational approaches to be deployed with the goal of minimizing organic
      substances and nitrogen levels in the outlet while using the minimum amount of
      energy. The proposed distributed control system, which is supervised by a
      Knowledge-Based Expert System (KBES) constructed with G2 (a tool for expert
      system development) and a back propagation BP artificial neural network, permits
      the on-line implementation of every operating strategy of the experimental
      system. A support vector machine (SVM) is applied to achieve pattern recognition.
      A set of experiments involving variable sludge retention time (SRT), hydraulic
      retention time (HRT) and dissolved oxygen (DO) was carried out. Using the
      proposed system, the amounts of COD, TN and NH4+-N in the effluent decreased by
      55%, 62% and 38%, respectively, compared to the usual operating conditions. These
      improvements were achieved with little energy cost because the performance of the
      treatment plant was optimized using operating rules implemented in real time.

PMID- 21862098
TI  - Assessing inter-laboratory comparability and limits of determination for the
      analysis of cyclic volatile methyl siloxanes in whole Rainbow Trout (Oncorhynchus
      mykiss).
AB  - Cyclic volatile methyl siloxanes (cVMS) are high volume production chemicals used
      in a wide range of industrial and consumer products. Three cVMS compounds (D4,
      D5, and D6) have and are undergoing environmental risk evaluations in several
      countries and have been proposed for legal regulation in Canada. As interest in
      monitoring concentrations of these chemicals in the environment increase, there
      is a need to evaluate the analytical procedures for cVMS in biological matrices
      in order to assess the quality of data produced. The purpose of this study was to
      determine laboratory testing performance for measuring residues of D4, D5, and D6
      in a standard set of fish homogenate samples and to estimate limits of
      determination for each substance. The samples sent to each laboratory consisted
      of homogenized whole body tissues of hatchery raised rainbow trout which were fed
      food fortified with D4, D5, and D6 (dosed) and trout that were fed standard food
      rations (control). The participants analyzed each sample using their analytical
      method of choice using their own standards and procedures for quantification and
      quality control. With a few exceptions, participating laboratories generated
      comparable results for D4, D5, and D6 in both the dosed and control samples
      having z-scores between 2 and -2. Method detection limits for the whole fish
      matrix were on average 2.4 ng g(-1) ww for D4, 2.3 ng g(-1) ww for D5, and 1.8 ng
      g(-1) ww for D6.

PMID- 21862099
TI  - Absorption of current use pesticides by snapping turtle (Chelydra serpentina)
      eggs in treated soil.
AB  - Reptiles often breed within agricultural and urban environments that receive
      frequent pesticide use. Consequently, their eggs and thus developing embryos may
      be exposed to pesticides. Our objectives were to determine (i) if turtle eggs are
      capable of absorbing pesticides from treated soil, and (ii) if pesticide
      absorption rates can be predicted by their chemical and physical properties.
      Snapping turtle (Chelydra serpentina) eggs were incubated in soil that was
      treated with 10 pesticides (atrazine, simazine, metolachlor, azinphos-methyl,
      dimethoate, chlorpyrifos, carbaryl, endosulfan (I and II), captan, and
      chlorothalonil). There were two treatments, consisting of pesticides applied at
      application rate equivalents of 1.92 or 19.2 kg a.i/ha. Eggs were removed after
      one and eight days of exposure and analyzed for pesticides using gas
      chromatography coupled with a mass selective detector (GC-MSD) or high
      performance liquid chromatography (HPLC). Absorption of pesticides in eggs from
      soil increased with both magnitude and duration of exposure. Of the 10
      pesticides, atrazine and metolachlor generally had the greatest absorption, while
      azinphos-methyl had the lowest. Chlorothalonil was below detection limits at both
      exposure rates. Our preliminary model suggests that pesticides having the highest
      absorption into eggs tended to have both low sorption to organic carbon or
      lipids, and high water solubility. For pesticides with high water solubility,
      high vapor pressure may also increase absorption. As our model is preliminary,
      confirmatory studies are needed to elucidate pesticide absorption in turtle eggs
      and the potential risk they may pose to embryonic development.

PMID- 21862100
TI  - Inconsistency and comprehensiveness of risk assessments for heavy metals in urban
      surface sediments.
AB  - Numerous indices have been developed to assess environmental risk of heavy metals
      in surface sediments, including the total content based geoaccumulation index
      (I(geo)), exchangeable fraction based risk assessment code (RAC), and biological
      toxicity test based sediment quality guidelines (SQGs). In this study, the three
      indices were applied to freshwater surface sediments from 10 sections along an
      urbanization gradient of the Grand Canal, China to assess the environmental risks
      of heavy metals (Cu, Pb, Zn, Cd, and Cr) and to understand discrepancies of risk
      assessment indices and urbanization effects regarding heavy metal contamination.
      Results showed that Cd, Zn, and Pb were the most enriched metals in urban
      sections assessed by I(geo) and over 95% of the samples exceeded the Zn and Pb
      thresholds of the effect range low (ERL) of SQGs. According to RAC, Cu, Zn, Cd,
      and Cr had high risks of adversely affecting the water quality of the Grand Canal
      due to their remarkable portions of exchangeable fraction in surface sediment.
      However, Pb showed a relative low risk, and was largely bounded to Fe/Mn oxides
      in the urban surface sediments. Obviously, the three assessment indices were not
      consistent with each other in terms of predicting environmental risks attributed
      to heavy metals in the freshwater surface sediments of this study. It is
      recommended that risk assessment by SQGs should be revised according to
      availability and site specificity. However, the combination of the three indices
      gave us a comprehensive understanding of heavy metal risks in the urban surface
      sediments of the Grand Canal.

PMID- 21862101
TI  - Impact of woodchip biochar amendment on the sorption and dissipation of pesticide
      acetamiprid in agricultural soils.
AB  - Pyrolysis of vegetative biomass into biochar and application of the more stable
      form of carbon to soil have been shown to be effective in reducing the emission
      of greenhouse gases, improving soil fertility, and sequestering soil
      contaminants. However, there is still lack of information about the impact of
      biochar amendment in agricultural soils on the sorption and environmental fate of
      pesticides. In this study, we investigated the sorption and dissipation of a
      neonicotinoid insecticide acetamiprid in three typical Chinese agricultural
      soils, which were amended by a red gum wood (Eucalyptus spp.) derived biochar.
      Our results showed that the amendment of biochar (0.5% (w/w)) to the soils could
      significantly increase the sorption of acetamiprid, but the magnitudes of
      enhancement were varied. Contributions of 0.5% newly-added biochar to the overall
      sorption of acetamiprid were 52.3%, 27.4% and 11.6% for red soil, paddy soil and
      black soil, respectively. The dissipation of acetamiprid in soils amended with
      biochar was retarded compared to that in soils without biochar amendment. Similar
      to the sorption experiment, in soil with higher content of organic matter, the
      retardation of biochar on the dissipation of acetamiprid was lower than that with
      lower content of organic matter. The different effects of biochar in agricultural
      soils may attribute to the interaction of soil components with biochar, which
      would block the pore or compete for binding site of biochar. Aging effect of
      biochar application in agricultural soils and field experiments need to be
      further investigated.

PMID- 21862102
TI  - Rapid-behaviour responses as a reliable indicator of estrogenic chemical toxicity
      in zebrafish juveniles.
AB  - Whereas biochemical and molecular parameters have been well recognised as
      important "signposts" of individual disturbance to endocrine disrupting
      chemical's (EDCs) exposure, behavioural endpoints are yet greatly overlooked as a
      routine tool in environmental risk assessment of EDCs. However, life histories
      are intimately associated with numerous inter- and intra-specific interactions,
      which invariably depend on the performance of effective behaviours. Within fish
      species, one of the most important factors influencing energy turnover earlier in
      the development is locomotor activity. This essential trait reflects the
      organism's ability to generate and coordinate the metabolic energy required for
      both reproductive and non-reproductive behaviours. Inappropriate movement
      responses due to toxic effects of contaminants may ultimately impact important
      ecological variables. Therefore, in the present study, the swimming bursts of
      zebrafish juveniles exposed for 40 d to the synthetic estrogen ethinylestradiol
      (EE(2)), tested at environmentally relevant concentrations (nominal
      concentrations of 0.5, 1 and 2 ng L(-1)), were investigated in order to address
      the potential of rapid-behaviour patterns as an effective response indicator of
      estrogenic endocrine disrupting chemical's exposure. This synthetic estrogen was
      selected due to its high prevalence in aquatic ecosystems, ability to mimic
      natural estrogens and proven record of causing negative effects in fish
      reproduction. The behavioural responses were compared with established endpoints
      used in the screening of EE(2) effects at adulthood. Results indicate that
      zebrafish juveniles' swimming activity was significantly decreased upon EE(2)
      exposure. Since reduced locomotion of zebrafish may impact foraging, predator
      avoidance, drift and transport, and even interfere with social and reproductive
      behaviours, a fitness decline of wild fish populations can ultimately be
      hypothesized. Furthermore, behavioural endpoints were found to display higher
      sensitivity to EE(2) than either vitellogenin gene induction or reproductive
      parameters determined at adulthood. Overall, the findings of this work not only
      demonstrate the power of high-throughput behavioural responses, able to act as
      sensitive early warning signals of EDC exposure, but also highlight the potential
      of behavioural endpoints in providing a more comprehensive and non-invasive
      measure of EDC's exposure.

PMID- 21862103
TI  - Effects of organic contaminants in reactive oxygen species, protein carbonylation
      and DNA damage on digestive gland and haemolymph of land snails.
AB  - The present study focused on early responses of land snails Eobania vermiculata
      to organic environmental contaminants, by investigating the use of a newly
      established method for the measurement of protein carbonylation as a new
      biomarker of terrestrial pollution, as well as by measuring the ROS production
      and the DNA damage. Land snails were exposed to different concentrations of
      chlorpyrifos, parathion-methyl or PAHs in vivo or in vitro in the laboratory. The
      susceptibility of exposed snails was increased in relation to oxidative stress
      induced by contaminants tested. A statistically significant increase in ROS
      production, protein carbonylation and DNA damage was revealed in the snails
      treated with pollutants, compared to the untreated ones. The results indicated
      the effectiveness of measuring ROS production and DNA damage and reinforce the
      application of the present ELISA method in organic terrestrial pollution
      biomonitoring studies.

PMID- 21862104
TI  - Salinity increases mobility of heavy metals in soils.
AB  - The effect of salinity induced by CaCl(2), MgCl(2), NaCl and Na(2)SO(4) on the
      mobility of Cu, Cd, Pb and Zn was studied. An increase of ionic strength by any
      salts promoted a higher release of Cd than the others metals. When CaCl(2) and
      NaCl were applied, Cd and Pb showed the highest degree of mobilization. When
      MgCl(2) was applied, Cd and Cu were mobilized the most. Finally, an increase of
      Na(2)SO(4) also promoted the strongest mobilization of Cd and Cu. As the total
      heavy metal content was higher, the percentage of Pb and Cu released upon
      salinization decreased, indicating that these metals are strongly bound to soil
      constituents. An increase of carbonates in the soil promoted a higher release of
      Pb for all used salts and for Zn when MgCl(2) and NaCl were used. This indicates
      that Pb and Zn are adsorbed on the surface of carbonate crystals. An increase of
      fine particles promoted a decrease of percentage of released Cd for all salts,
      indicating that Cd is strongly retained in the fine fractions. The main mechanism
      regulating Pb and Cd mobility was competition with Ca(2+) for sorption sites
      followed for metal chloro-complexation, association between the Cd/Pb-sulfates
      and competition with Mg(2+). The main mechanism regulating Cu mobility was the
      formation of Cu-sulfate, followed by competition with cations (Mg > Ca) and
      chloride. For Zn, competition with Ca(2+) for sorption sites was the most
      important process for its mobility; followed by Zn-sulfate association and,
      finally, chloride and competition with Mg with the same effect.

PMID- 21862105
TI  - Assessing the value of Earth Observation for managing coral reefs: an example
      from the Great Barrier Reef.
AB  - The Integrated Global Observing Strategy (IGOS, 2003) argues that further
      investments in Earth Observation information are required to improve coral reef
      protection worldwide. The IGOS Strategy does not specify what levels of
      investments are needed nor does it quantify the benefits associated with better
      protected reefs. Evaluating costs and benefits is important for determining
      optimal investment levels and for convincing policy-makers that investments are
      required indeed. Few studies have quantitatively assessed the economic benefits
      of Earth Observation information or evaluated the economic value of information
      for environmental management. This paper uses an expert elicitation approach
      based on Bayesian Decision Theory to estimate the possible contribution of global
      Earth Observation to the management of the Great Barrier Reef. The Great Barrier
      Reef including its lagoon is a World Heritage Area affected by anthropogenic
      changes in land-use as well as climate change resulting in increased flows of
      sediments, nutrients and carbon to the GBR lagoon. Since European settlement,
      nutrient and sediment loads having increased 5-10 times and the change in water
      quality is causing damages to the reef. Earth Observation information from ocean
      and coastal color satellite sensors can provide spatially and temporally dense
      information on sediment flows. We hypothesize that Earth Observation improves
      decision-making by enabling better-targeted run-off reduction measures and we
      assess the benefits (cost savings) of this improved targeting by optimizing run
      off reductions under different states of the world. The analysis suggests that
      the benefits of Earth Observation can indeed be substantial, depending on the
      perceived accuracy of the information and on the prior beliefs of decision
      makers. The results indicate that increasing informational accuracy is the most
      effective way for developers of Earth Observation information to increase the
      added value of Earth Observation for managing coral reefs.

PMID- 21862106
TI  - Policy makers should take into account the enormous burden of disease caused by
      toxic chemicals emitted from waste incinerator.

PMID- 21862107
TI  - Comparative effectiveness of rituximab in combination with either methotrexate or
      leflunomide in the treatment of rheumatoid arthritis.
AB  - OBJECTIVE: To compare the effectiveness and safety of a combination of rituximab
      (RTX) with either methotrexate (MTX) or leflunomide (LEF) in the treatment of
      patients with active rheumatoid arthritis (RA) and inadequate response to anti
      tumor necrosis factor agents or traditional disease-modifying antirheumatic drugs
      (DMARD) in a real-world setting. METHODS: Data from 77 consecutive unselected
      patients with active RA and treated with at least 1 cycle of RTX (1 g * 2 weeks)
      plus MTX or LEF were retrospectively collected. A comparative study between the 2
      combinations of treatment (RTX+MTX and RTX+LEF) was performed at 6 months of
      follow-up considering 3 outcomes: the improvement of RA disease activity, the
      evolution of functional disability, and the tolerability and side effect profile.
      RESULTS: Of the 77 patients, 45 received RTX+MTX and 32 RTX+LEF. At baseline
      there were no significant differences between the groups in terms of the main
      clinical and laboratory data, or in the number of previous DMARD and anti-tumor
      necrosis factor agents used. At 6 months of follow-up, we did not find
      significant differences between the 2 combinations in the evolution of RA disease
      activity (DAS28 response, according to the European League Against Rheumatism
      (EULAR) improvement criteria) and functional disability progression (health
      assessment questionnaire) over time. Minor adverse events occurred in 9% of
      RTX+MTX patients and in 9% of RTX+LEF patients. None of the patients had serious
      adverse events and none discontinued the treatment during the study period.
      CONCLUSIONS: Our preliminary data support the view that LEF is a useful
      alternative if MTX is contraindicated, since its effectiveness and safety seem
      similar.

PMID- 21862108
TI  - New onset of uveitis during anti-tumor necrosis factor treatment for rheumatic
      diseases.
AB  - Uveitis may be associated with various inflammatory diseases. Previous reports
      suggested that tumor necrosis factor (TNF) blockers, especially anti-TNF
      monoclonal antibodies, may reduce the incidence of uveitis flares in some
      inflammatory diseases. Under these circumstances, de novo occurrence, ie, new
      onset of the first episode of uveitis under anti-TNF therapy, is uncommon.
      OBJECTIVES: The aim of this study was to collect cases of new onset of uveitis
      under anti-TNF therapy, using a nationwide network, to describe these cases, and
      to gather with cases reported in the literature. METHODS: All French
      rheumatologists, pediatric rheumatologists, and internal medicine practitioners
      registered on the Club Rhumatismes et Inflammation web site were contacted in an
      attempt to declare the cases of new onset of uveitis, diagnosed by an
      ophthalmologist, in patients treated with TNF blockers. The analysis of the
      literature was performed through PubMed database and manual research. RESULTS:
      Thirty-one cases were recorded, 19 men, mean age 43 (5-70) years, occurring in
      ankylosing spondylitis (19 cases), psoriatic arthritis (4 cases), rheumatoid
      arthritis (6 cases), juvenile idiopathic arthritis (2 cases). The TNF blocker at
      the time of uveitis was etanercept 23 times, adalimumab 3 times, infliximab 5
      times, with a mean total duration of exposure to anti-TNF agents of 27 (4-96)
      months at uveitis occurrence. Most of the patients were good responders to TNF
      blockers at the time of uveitis onset. Analysis of the literature revealed 121
      similar cases published in English. CONCLUSION: Uveitis occurs de novo under anti
      TNF therapy mainly in spondyloarthropathies, but also in rheumatoid arthritis and
      juvenile idiopathic arthritis patients and more frequently under etanercept.

PMID- 21862109
TI  - Determination of cut-off levels for on-clopidogrel platelet aggregation based on
      functional CYP2C19 gene variants in patients undergoing elective percutaneous
      coronary intervention.
AB  - INTRODUCTION: Carriers of reduced-function CYP2C19 allele on antiplatelet therapy
      show diminished platelet inhibition and higher rate of clinical risk. The purpose
      of this study was to determine cut-off levels of VerifyNow P2Y12 system
      associated with effective inhibition of on-clopidogrel platelet aggregation to
      predict carriers of CYP2C19 reduced-function allele among patients undergoing
      percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We enrolled 202
      consecutive patients with stable coronary artery disease (CAD) undergoing PCI and
      treated with clopidogrel. All patients underwent CYP2C19 genotyping and
      measurement of residual platelet aggregation by VerifyNow system. RESULTS:
      Carriers of CYP2C19 reduced-function allele constituted 131 (65%) of 202 CAD
      patients. Platelet inhibition measured by P2Y12 reaction units (PRU) and
      %inhibition was diminished in carriers compared with noncarriers (PRU: 290.0+/
      81.2 vs 217.6+/-82.4, p<0.001, %inhibition: 17.9+/-17.8 vs 35.5+/-22.8, p<0.001,
      respectively). Multiple logistic regression analysis identified PRU and
      %inhibition as significant predictors of carrier state [odds ratio (OR) 4.95; 95%
      confidence interval (95%CI): 2.49 to 9.85; p<0.001, OR 5.55; 95%CI: 2.80 to
      10.99; p<0.001, respectively]. Receiver-operating characteristic analysis showed
      that PRU and %inhibition were significant predictors of carrier state [area under
      the curve (AUC) 0.736 (95%CI: 0.664 to 0.808; p<0.001), AUC 0.727 (95%CI: 0.651
      to 0.803; p<0.001), respectively]. The cut-off levels of PRU and %inhibition were
      256 and 26.5% for the identification of carriers. CONCLUSIONS: Our results
      suggested that the cut-off levels of PRU and %inhibition to discriminate carriers
      of CYP2C19 reduced-function allele from noncarriers are potentially useful
      clinically to provide optimal clopidogrel therapy in patients with stable CAD
      undergoing PCI.

PMID- 21862110
TI  - Anticoagulant effects of an antidiabetic drug on monocytes in vitro.
AB  - INTRODUCTION: Monocyte- and microparticle (MP)-associated tissue factor (TF) is
      upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and
      alternatively spliced TF (asTF) and increases MP release from monocytes. Using
      LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a
      sulfonylurea used to treat diabetes type 2, might possess anticoagulant
      properties. METHODS: We studied the effects of glibenclamide on cell- and
      supernatant-associated procoagulant activity (Factor Xa-generating assay and clot
      formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western
      blot) and on cell viability and MP release (flow cytometry). RESULTS:
      Glibenclamide dose-dependently decreased procoagulant activity of cells and
      supernatants. The reduction in cellular procoagulant activity coincided with
      reduced expression of TF and asTF in cells, whereas cell viability remained
      almost unchanged. The glibenclamide-induced reduction in procoagulant activity of
      supernatants appeared to be associated with a decreased number of released MPs.
      CONCLUSIONS: Reduction of monocyte- and supernatant-associated procoagulant
      activity by glibenclamide is associated with decreased expression of TF and asTF
      and possibly with a reduced MP number. Our data indicate that glibenclamide
      reduces the prothrombotic state in LPS-stimulated monocytes in vitro.
      Glibenclamide might therefore also have an anticoagulant effect in vivo, but this
      needs to be further evaluated.

PMID- 21862111
TI  - Attitudes towards and practice of venous thromboembolism prevention in general
      internal medicine wards: a multinational survey from member countries of the
      European Federation of Internal Medicine.
AB  - INTRODUCTION: Hospitalised patients in Internal Medicine departments are at risk
      of venous thromboembolism (VTE). Adherence to risk stratification methods is
      poor. We conducted a survey among Internists from member countries of the
      European Federation of Internal Medicine (EFIM) to assess current knowledge and
      attitude towards VTE prevention. METHODS: A multinational survey of Internists
      affiliated to EFIM. RESULTS: 226 physicians from 30 countries were included.
      Seventy nine percent of the physicians were aware of clinical guidelines to
      prevent VTE. Most considered their knowledge of the guidelines to be moderate.
      Many had not updated their knowledge recently. The magnitude of the clinical
      problem was over- and underestimated by many (12.2% and 40.1%, respectively).
      Only 46.7% thought their patients were mostly receiving proper prophylaxis. Sixty
      four percent worked in departments without a formal VTE prophylaxis program. Risk
      of bleeding, lack of awareness and lack of decision support systems were the
      three most common reasons for deferring treatment (88.6%, 32.3% and 27.9%,
      respectively). Most of the participants stated that they strongly believe in VTE
      prophylaxis as an intervention that prevents morbidity and mortality.
      CONCLUSIONS: Despite general awareness of clinical guidelines, many medical wards
      do not have formal risk assessment methodologies incorporated into their
      operative workflow. This gap, as well as fear of complications, may be one of the
      reasons for the low rates of adherence reported by physicians. We speculate that
      perhaps current guidelines have not been accepted by Internists due to paucity of
      well defined and validated risk assessment tools.

PMID- 21862112
TI  - Normalized coagulation markers and anticoagulation proteins in children with
      severe beta-thalassemia disease after stem cell transplantation.
AB  - The hypercoagulable state is well recognized in patients with severe beta
      thalassemia disease. One of the mechanisms of chronic hypercoagulable state is
      the abnormal expression of phosphatidylserine on red blood cells (RBC). This
      study aimed to determine the coagulable state in patients with severe beta
      thalassemia disease following successful stem cell transplantation (SCT).
      Subjects were classified into three groups: normal controls (NC), beta
      thalassemia disease receiving regular transfusion (Thal-RT) and beta-thalassemia
      disease post SCT (Thal-SCT). Sixty eight subjects, aged 3-17years, consisting of
      21 NC, 28 Thal-RT and 19 Thal-SCT were enrolled. After SCT, the annexin V level
      in Thal-SCT was normalized. At the median follow-up time of 70.3 (50.9-84.2)
      months after SCT, the levels of coagulation markers (thrombin antithrombin
      complex, prothrombin fragment and D-dimer) and anticoagulation proteins (protein
      C, S and antithrombin activities) returned to the levels similar to controls.

PMID- 21862113
TI  - Time dependence of clopidogrel loading effect: platelet activation versus
      platelet aggregation.

PMID- 21862114
TI  - Duplicated vena cava with tumor thrombus from renal cancer: use of venogram for
      safer operative planning.
AB  - Renal and adrenal tumors can invade into the inferior vena cava (IVC) in 4%-10%
      of cases. Consequently, urologists must remain well versed in the anatomy of the
      IVC. The IVC develops embryologically from the coordinated growth and regression
      of a series of veins. Occasionally, these veins can persist, creating vena caval
      abnormalities. A completely duplicated caval system is 1 of these variations. We
      present a case of renal cell carcinoma with tumor thrombus extending into a
      duplicated IVC and show how understanding of venous drainage and pertinent
      imaging can aid with a successful outcome.

PMID- 21862115
TI  - Social networks lack useful content for incontinence.
AB  - OBJECTIVE: To assess the incontinence resources readily available for patients
      among social networks. Social networks allow users to connect with each other and
      share content and are a widely popular resource on the Internet. These sites
      attract millions of users; however, social media are underused in the healthcare
      industry. METHODS: A search for "incontinence" was performed on Facebook,
      Twitter, and YouTube in September 2010. The first 30 results were reviewed for
      each. The results were evaluated as useful or not useful and additionally
      catalogued as healthcare professionals, commercial products, or complementary and
      alternative medicine resources. RESULTS: On Facebook, 4 results (13%) were
      informative, 12 (40%) advertised commercial incontinence products, and 14 (47%)
      had no usable information. Of the live "tweets" reviewed on Twitter, 18 (60%)
      linked to incontinence-related healthcare information (none were from, or
      referred one to, healthcare professionals), 9 (30%) advertised for commercial
      incontinence products, 1 (3%) advertised complementary and alternative medicine
      resources, and 2 (7%) were humorous. Of 4 Twitter user results, 1 was comic, 1
      provided incontinence-related health information, and 2 were incontinence medical
      supply companies. There were 14 (47%) informational YouTube videos, of which 9
      came from healthcare professionals or professional organizations. Of the
      remainder, 12 (40%) were commercial, 1 (3%) advertised complementary and
      alternative medicine resources, and the remaining 3 (10%) were not useful.
      CONCLUSION: The results of our study show that social networks have insufficient
      useful incontinence content, especially from healthcare professionals and
      incontinence organizations. Medical professionals and societies should target
      these avenues to reach and educate patients.

PMID- 21862116
TI  - Laparoscopic nephrectomy in xanthogranulomatous pyelonephritis: 7-year single
      surgeon outcome.
AB  - OBJECTIVE: To evaluate the outcome of laparoscopic nephrectomy in patients with
      xanthogranulomatous pyelonephritis (XGPN). METHODS: The medical and procedural
      records of patients with pathologically confirmed XGPN from February 2004 to
      December 2010 were reviewed retrospectively. During this period, 19 patients
      (mean age 37.5 years, range 14-77) underwent surgical management of XGPN. The
      records of the clinical history, mode of presentation, surgical management,
      hospital stay, and complications were analyzed. RESULTS: Laparoscopic nephrectomy
      was performed successfully in 14 patients (73.2%); 5 patients required conversion
      to open surgery. Of these 5 patients, 3 electively underwent conversion to open
      surgery because of nonprogression of the procedure, and in 2 patients, conversion
      was performed on an emergency basis because of bleeding from hilar vessels in 1
      patient and diaphragmatic injury in the other. The operative time was 284 minutes
      (range 181-340), with a mean estimated blood loss of 220 mL (range 90-500) and
      mean analgesic (tramadol) requirement of 150 mg (range 50-500). Clavien grade I
      complications occurred in 2 patients, grade II in 3, and grade IIIa in 1 patient.
      Two patients had grade IVb complications. One patient required a blood
      transfusion. The mean hospital stay duration and the return to routine activities
      was 4.4 days (range 2-37) and 21 days (range 12-66), respectively. CONCLUSION:
      Laparoscopic nephrectomy, although challenging, can be performed safely in most
      patients with XGPN. A greater conversion rate and longer operative time should be
      expected, and early conversion to an open approach might be required in difficult
      cases owing to a failure to proceed.

PMID- 21862117
TI  - Bilateral primary adrenal lymphoma accompanying hypertension.
AB  - Primary adrenal lymphoma (PAL) accompanied by hypertension is extremely rare. We
      present a case of PAL with hypertension, whom was treated with bilateral
      adrenalectomy and a combination of the modified Appleby operation and
      chemotherapy. Computed tomography and biopsy is helpful to aid diagnosis.

PMID- 21862118
TI  - Incidentally discovered osseous metaplasia within high-grade urothelial carcinoma
      of the bladder.
AB  - A 66-year-old male presented with gross hematuria and acute renal failure
      secondary to bilateral ureteral obstruction. Further work-up revealed muscle
      invasive urothelial carcinoma. Pathologic examination following radical
      cystoprostatectomy revealed high grade urothelial carcinoma with focal tumor
      associated stromal osseous metaplasia. Reactive bone formation within urothelial
      carcinoma is a very rare clinical entity. Although typically benign, the presence
      of mature bone elements warrants thorough examination for sarcomatoid components.

PMID- 21862119
TI  - Angiogenesis and molecular markers in advanced epithelial ovarian cancer: a
      retrospective study.
AB  - OBJECTIVE: The role of molecular markers in ovarian cancer is still a matter of
      debate. Angiogenesis is a necessary condition for tumor growth. Hypoxia induces
      angiogenesis, and cyclooxygenase-2 (COX-2), p53 and HER2 are involved in cancer
      proliferation and angiogenesis regulation. The aims of this study were to
      evaluate the relationship between intratumoral microvessel density (IMD) and the
      expression of molecular markers that affect angiogenesis (COX-2, p53 and HER2) in
      advanced epithelial ovarian cancer (EOC), to analyze their prognostic and
      predictive value and their association with clinicopathological features, such as
      serum hemoglobin level at diagnosis (Hb). METHODS: Immunohistochemical staining
      with CD34 (for IMD), COX-2, p53 and HER2 antibodies was performed in 113 patients
      with advanced EOC who had undergone primary surgery. Clinicopathological data
      were collected and statistical analyses were performed. RESULTS: Neither IMD, COX
      2 nor HER2 had any predictive or prognostic value in EOC. A relationship that
      approached statistical significance was found between p53 expression and a
      complete response to treatment (p=0.05). p53 expression and tumor grade were
      inversely associated (p=0.012). Hb<12g/dl had predictive value (p=0.02).
      CONCLUSIONS: In our series IMD, COX-2 and HER2 had neither prognostic nor
      predictive value in advanced EOC. p53 and Hb may be predictive factors. The
      results and clinical usefulness of immunohistochemistry are controversial.
      Further evaluations are required to determine whether the serum levels of
      molecular markers correlate with the results of immunohistochemical assays and
      whether they offer any prognostic and/or predictive value. Targeted therapy
      remains the ultimate goal of these studies.

PMID- 21862120
TI  - Elucidating the interplay between DNA-condensing and free polycations in gene
      transfection through a mechanistic study of linear and branched PEI.
AB  - In the present study we compare LPEI and BPEI characteristics related to DNA
      condensation and their role as free polycation chains in gene transfection. Using
      radioactive (32)P labeled DNA, we investigated the effect of free PEI chains on
      the cellular uptake of polyplexes. Our investigations show different properties
      of BPEI and LPEI polyplexes in condensation and de-condensation processes as well
      as in cellular uptake, which was tightly correlated with transfection efficiency.
      In agreement with earlier reports we find all DNA to be condensed at N/P = 3.
      Further added PEI chains remain free in solution. We found that both the cellular
      uptake and gene transfection of BPEI polyplexes is much more efficient than LPEI
      polyplexes at a low N/P ratio of 3 (i.e., without free PEI chains). When N/P is
      high (10, with 7 portions of free PEI), the LPEI and BPEI polyplexes have similar
      transfection efficiency even though the cellular uptake of the LPEI polyplexes is
      significantly lower. In addition, we found that addition of free short or long
      PEI chains (2.5 and 25 kDa) leads to a comparable gene transfection efficiency.

PMID- 21862121
TI  - Effects of chitosan-nanoparticle-mediated tight junction opening on the oral
      absorption of endotoxins.
AB  - Recently, we reported a pH-responsive nanoparticle (NP) system shelled with
      chitosan (CS), which could effectively increase the oral absorption of insulin
      and produce a hypoglycemic effect, presumably due to the CS-mediated tight
      junction (TJ) opening. It has been often questioned whether CS can also enhance
      the absorption of endotoxins present in the small intestine. To address this
      concern, we studied the effect of CS NPs on the absorption of lipopolysaccharide
      (LPS), the most commonly found toxin in the gastrointestinal tract. To follow
      their biodistribution by the single-photon emission computed tomography/computed
      tomography, LPS and insulin were labeled with (99m)Tc-pertechnetate ((99m)Tc-LPS)
      and (123)iodine ((123)I-insulin), respectively. The (99m)Tc-LPS was ingested 1 h
      prior to the administration of the (123)I-insulin-loaded NPs to mimic the
      physiological conditions. The confocal and TEM micrographs show that the orally
      administered CS NPs were able to adhere and infiltrate through the mucus layer,
      approach the epithelial cells and mediate to open their TJs. The radioactivity
      associated with LPS was mainly restricted to the gastrointestinal tract, whereas
      (123)I-insulin started to appear in the urinary bladder at 3 h post
      administration. This observation indicates that the insulin-loaded in CS NPs can
      traverse across the intestinal epithelium and enter the systemic circulation,
      whereas LPS was unable to do so, probably because of the charge repulsion between
      the anionic LPS in the form of micelles and the negatively charged mucus layer.
      Our in vivo toxicity study further confirms that the enhancement of paracellular
      permeation by CS NPs did not promote the absorption of LPS. These results suggest
      that CS NPs can be used as a safe carrier for oral delivery of protein drugs.

PMID- 21862122
TI  - Enhanced osseointegration of titanium implant through the local delivery of
      transcription factor SATB2.
AB  - Titanium implants are widely used in dentistry and orthopedic surgery.
      Nevertheless, bone regeneration around the implant is a relatively slow process,
      after placement. This study assessed whether SATB2 can enhance osseointegration
      of a titanium implant. To determine the effect of SATB2 in implant integration,
      two different viruses encoding SATB2 (PBABE-Satb2 virus or RCAS-Satb2 virus) were
      locally administered to the bone defect prior to titanium implant placement in
      our established transgenic TVA mice. Seven and 21 days post implantation, the
      femurs were isolated for quantitative real-time RT-PCR, H&E staining,
      immunohistochemical (IHC) staining, and microcomputed tomography (microCT)
      analysis. Quantitative real-time RT-PCR results demonstrated that the in vivo
      overexpression of SATB2 enhanced expression levels of potent osteogenic
      transcription factors and bone matrix proteins. We also found that 21 days after
      implantation, there were no significant differences in the expression levels of
      SATB2, Osx, Runx2, COLI, OC, and BSP between the RCAS-Satb2 group and the RCAS
      group. Histological analysis showed that SATB2 overexpression significantly
      enhanced new bone formation and bone-to-implant contact after implantation. IHC
      staining analysis revealed that forced expression of SATB2 increased the number
      of BSP-positive cells surrounding the implant. MicroCT analysis demonstrated that
      in vivo overexpression of SATB2 significantly increased the density of the newly
      formed bone surrounding the implant. These results conclude that in vivo
      overexpression of SATB2 significantly accelerates osseointegration of titanium
      implants and SATB2 can serve as a potent molecule in promoting tissue
      regeneration.

PMID- 21862124
TI  - Galectin-8 is expressed by villous and extravillous trophoblast of the human
      placenta.
AB  - Galectins (gals) as multifunctional animal lectins are of great potential
      significance for establishment and function of the placenta, due to their
      capacity to modulate cellular functions including proliferation, adhesion, and
      invasion. Human trophoblast is known to express gal-1, gal-3 and gal-13 proteins,
      as well as mRNAs for gal-14, -16 and -17. This study was undertaken to establish
      cellular distribution of gal-8, not previously associated with trophoblast, since
      we have recently detected gal-8 RNA and protein in cytotrophoblast cell material.
      Results of immunolocalization showed that gal-8 was expressed by villous and
      extravillous cytotrophoblast.

PMID- 21862123
TI  - Liposomes for HIV prophylaxis.
AB  - There are approximately 33.4 million adults living with HIV worldwide of which an
      estimated 15.7 million are women. Although there has been enormous progress in
      the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of
      paramount importance, but vaccine-based and microbicidal approaches are still in
      their infancy. Since women acquire the virus largely through sexual intercourse,
      we developed liposomal systems potentially suitable for intra-vaginal use to
      prevent HIV-1 infection. We formulated liposomes from a range of naturally
      occurring and synthetic lipids with varying physicochemical properties, and
      tested their ability to inhibit infection of transformed cells that express
      receptors specific to the virus. We identified formulations with the most
      favorable balance between decreasing HIV infection and causing cytotoxicity (i.e.
      therapeutic index). The therapeutic index improved with increasing cardiolipin
      content, and degree of unsaturation. Tissue reaction to these formulations was
      benign after intra-vaginal instillation in an in vivo female mouse model. These
      results support the potential use of cardiolipin-based liposomes enriched with
      synthetic lipids as microbicides for the prevention of HIV infection in women.

PMID- 21862125
TI  - Central neuropeptide Y infusion and melanocortin 4 receptor antagonism inhibit
      thyrotropic function by divergent pathways.
AB  - Weight loss inhibits thyrotropic function and reduces metabolic rate, thereby
      contributing to weight regain. Under negative energy balance there is an increase
      in the hypothalamic expression of both neuropeptide Y (NPY) and agouti related
      peptide (AgRP), the endogenous antagonist of melanocortin 4 (MC4) receptors. Both
      NPY and MC4 receptor antagonism reduce thyrotropic function centrally, but it is
      not known whether these pathways operate by similar or distinct mechanisms. We
      compared the time-course of effects of acute or chronic intracerebroventricular
      (ICV) administration of NPY (1.2 nmol acute bolus, or 3.5 nmol/day for 6 days) or
      the MC4 receptor antagonist HS014 (1.5 nmol bolus, or 4.8 nmol/day) on plasma
      concentrations of thyroid stimulating hormone (TSH) or free thyroxine (T4) in
      male rats pair-fed with vehicle-infused controls. These doses equipotently
      induced hyperphagia in acute studies, reduced latency to feed, and increased
      white adipose tissue mass after 6 days of infusion. Acute central NPY but not
      HS014 administration significantly reduced plasma TSH concentrations within 30-60
      min and plasma free T4 levels within 90-120 min. These inhibitory effects were
      sustained for up to 5-6 days of continuous NPY infusion. HS014 induced a
      transient decrease in plasma free T4 levels that was observed only after 1-2 days
      of continuous ICV infusion. While both NPY and HS014 significantly increased
      corticosteronemia within an hour after ICV injection, the effect of NPY was
      significantly more pronounced and was sustained for up to 4 days of
      administration. Both NPY and HS014 significantly decreased the brown adipose
      tissue protein levels of uncoupling protein-3. We conclude that central NPY and
      MC4 antagonism decrease thyrotropic function via partially distinct mechanisms
      with different time courses, possibly involving glucocorticoid effects of NPY.
      MC4 receptor antagonism increases adiposity via pathways independent of increased
      food intake or changes in circulating concentrations of TSH, free T4 or
      corticosterone.

PMID- 21862126
TI  - Parental cognitive impairment and child maltreatment in Canada.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of parental
      cognitive impairment in cases opened for child maltreatment investigation in
      Canada, and to examine the relationship between parental cognitive impairment and
      maltreatment investigation outcomes including substantiation, case disposition
      and court application. METHODS: The method was secondary analysis of the Canadian
      Incidence Study of Child Abuse and Neglect (CIS-2003) core-data, which is derived
      from a multi-stage stratified cluster sample of 11,562 child maltreatment
      investigations. RESULTS: Parental cognitive impairment was noted in 10.1% of
      sampled cases that were opened for child maltreatment investigation in 2003, and
      in 27.3% of sampled cases that resulted in child welfare court application.
      Neglect was the most common cause of concern. With child and case characteristics
      held constant, parental cognitive impairment predicted investigation outcomes.
      The data further suggest that the relationship between parental cognitive
      impairment and investigation outcomes was partially mediated by perceived parent
      non-cooperation, mental health issues and low social support. CONCLUSIONS: The
      number of children who are living with a parent with cognitive impairment and who
      are referred for protective services is thought to be increasing. Building
      systems capacity to support parents with cognitive impairment and promote child
      wellbeing is therefore essential to containing the human and economic costs of
      maltreatment and out-of-home care. PRACTICE IMPLICATIONS: A broad-spectrum
      approach is needed to support parents with cognitive impairment and their
      children. Equipping services with the knowledge, skills, and mandate they need to
      deliver evidence-based parent training is vital. However, strategies are also
      needed to tackle discrimination, alleviate family poverty, strengthen the social
      ties of parents with cognitive impairment and in turn, improve the life chances
      of their children.

PMID- 21862127
TI  - Sexual, physical, verbal/emotional abuse and unexplained chest pain.
AB  - OBJECTIVES: Approximately one third of patients with non cardiac chest pain
      (NCCP) report a history of abuse, however no data exists on the prevalence of
      abuse among people with unexplained chest pain in the general population. We
      aimed to determine if there is a relationship between childhood sexual, physical,
      emotional abuse and unexplained chest pain, and to identify whether any potential
      relationship is being driven by an association with psychological distress.
      METHODS: Subjects were identified from 2 previous random population surveys that
      included people with irritable bowel syndrome (IBS) and/or functional dyspepsia
      (FD) and healthy controls. People in the unexplained chest pain group (n=27) had
      chest pain in the past 12months that was not heartburn or heart disease. People
      in the comparison group (n=60) did not have chest pain for more than 12months.
      Self-reported abuse and psychological variables were assessed using validated
      measures. RESULTS: Emotional/verbal abuse (20.8% versus 4.4%, P=0.032) and
      physical abuse (16.7% versus 2.2%, P=0.028) were significantly more common in
      people with unexplained chest pain versus the comparison group. Only a history of
      emotional/verbal abuse was a significant independent predictor of meeting
      criteria for unexplained chest pain (OR=5.66; 95%CI 1.01-31.80, P=0.049) even
      after controlling for IBS and/or FD (OR=5.45; 95%CI 0.96-30.83, P=.05), but not
      when depression was controlled for (OR=4.70; 95%CI 0.90-27.61), P=0.08.
      CONCLUSIONS: A history of childhood emotional/verbal abuse is a risk factor for
      having unexplained chest pain but the association may be moderated by
      psychological distress, specifically depression.

PMID- 21862128
TI  - Studies and evaluation of the potential toxicity of decabromodiphenyl ethane to
      five aquatic and sediment organisms.
AB  - The potential toxicity of decabromodiphenyl ethane (DBDP-Ethane) was explored in
      5 types of organisms residing in the water column and/or sediment, e.g.
      Oncorhynchus mykiss, Pseudokirchneriella subcapitata, Daphnia magna, Chironmus
      riparius, and Lumbriculus variegates. Fish, algae or Daphnia were unaffected by
      acute exposures to water accommodated fractions of 110mg DBDP-Ethane/L. Chronic
      exposure to DBDP-Ethane at the highest dose tested, 5000mg/kg dry sediment, did
      not affect midge mean development times, emergence or development rates or
      oligochaete survival, reproduction or dry weight. The chronic EC50, LOEC and NOEC
      were >=5000mg/kg in the two sediment species. Applying an assessment factor of
      50, the unbounded predicted no effect concentration (PNEC(sediment)) was 100mg/kg
      dry sediment. The calculated PNEC indicates DBDPE-Ethane presents little risk to
      sediment organisms. These results add to DBDP-Ethane's existing database in the
      terrestrial compartment and mammals.

PMID- 21862129
TI  - Reproductive effects of the water-accommodated fraction of a natural gas
      condensate in the Indo-Pacific reef-building coral Pocillopora damicornis.
AB  - Toxic effects of the water-accommodated fraction (WAF) of a natural gas
      condensate on the reproduction of the brooding coral Pocillopora damicornis were
      studied in short-term (24 h) laboratory experiments. Coral fragments were exposed
      to varying concentrations of condensate WAF during different reproductive phases:
      gametogenesis, early embryogenesis, and late embryogenesis (when nighttime
      planulation occurs). During gametogenesis, exposure to condensate WAF did not
      inhibit subsequent production of larvae. On the other hand, exposure to >25% WAF
      of gravid corals, at early and late embryogenesis, resulted in abortion and early
      release of larvae, respectively, with higher percentages of larvae expelled in
      fragments treated with higher concentrations of condensate WAF at least 3h after
      onset of exposure. Aborted larvae during early embryogenesis were 'premature', as
      they are of small size (0.06+/-0.03 mm3), low metamorphic competency (54%), and
      white in coloration, with a pale brown oral end (indicating low density of
      zooxanthellae). Those larvae released at the latter part of embryogenesis are
      bigger in size (0.22+/-0.08 mm3), possess 100% metamorphic competency, and are
      brown in coloration (high density of zooxanthellae). Aside from direct effects on
      reproduction, fragment mortality index was higher in samples exposed to higher
      concentrations of condensate WAF (>25%), hence lowering the number of potentially
      reproducing polyps. Altogether, exposure to >25% natural gas condensate WAF for
      at least 3h can potentially disrupt the replenishment of coral populations due to
      negative effects on reproduction and early life processes.

PMID- 21862130
TI  - Mercury accumulation patterns and biochemical endpoints in wild fish (Liza
      aurata): a multi-organ approach.
AB  - The integration of bioaccumulation and effect biomarkers in fish has been
      proposed for risk evaluation of aquatic contaminants. However, this approach is
      still uncommon, namely in the context of mercury contamination. Furthermore, a
      multi-organ evaluation allows an overall account of the organisms' condition.
      Having in mind the organs' role on metal toxicokinetics and toxicodynamics,
      gills, liver and kidney of golden grey mullet (Liza aurata) were selected and
      mercury accumulation, antioxidant responses and peroxidative damage were
      assessed. Two critical locations in terms of mercury occurrence were selected
      from an impacted area of the Ria de Aveiro, Portugal (L1, L2), and compared with
      a reference area. Although kidney was the organ with the highest mercury load,
      only gills and liver were able to distinguish mercury accumulation between
      reference (R) and contaminated stations. Each organ demonstrated different
      mercury burdens, whereas antioxidant responses followed similar patterns. Liver
      and kidney showed an adaptive capacity to the intermediate degree of
      contamination/accumulation (L1) depicted in a catalase activity increase. In
      contrast, none of the antioxidants was induced under higher
      contamination/accumulation (L2) in any organ, with the exception of renal GST.
      The lack of lipid peroxidation increase observed in the three organs denunciates
      the existence of an efficient antioxidant system. However, the evidences of
      limitations on antioxidants performance at L2 cannot be overlooked as an
      indication of mercury-induced toxicity. Having in mind the responses of the three
      organs, CAT revealed to be the most suitable parameter for identifying mercury
      exposure in the field. Overall, organ-specific mercury burdens were unable to
      distinguish the intermediate degree of contamination, while antioxidant responses
      revealed limitations on signalizing the worst scenario, reinforcing the need to
      their combined use.

PMID- 21862131
TI  - Diversity of Bartonella species detected in arthropod vectors from animals in
      Australia.
AB  - A variety of Bartonella species were detected in two species of ticks and three
      species of fleas collected from marsupial hosts; brush-tailed bettong or woylie
      (Bettongia penicillata) and western barred bandicoots (Perameles bougainville)
      and from a rodent host; Rattus fuscipes in Western Australia. Bartonella species
      were detected using nested-PCR of the gltA gene and the 16S-23S ribosomal
      internal transcribed spacer region (ITS), and species were characterized using
      DNA sequencing of the 16S rRNA, gltA, rpoB, ftsZ genes and the ITS region.
      Bartonella rattaustraliani and B. coopersplainsensis were detected in Ixodes spp.
      ticks and fleas (Stephanocircus pectinipes) respectively collected from rodents.
      Two novel Bartonella species were detected from marsupials; Candidatus Bartonella
      woyliei n. sp. was detected in both fleas (Pygiopsylla hilli) and ticks (Ixodes
      australiensis) collected from woylies and Candidatus Bartonella bandicootii n.
      sp. was detected in fleas (Pygiopsylla tunneyi) collected from western barred
      bandicoots. Concatenated phylogenetic analysis of all 5 loci clarified the
      marsupial cluster of Bartonella species in Australia and confirmed the species
      status of these two Bartonella species in ticks and fleas from woylies and
      western barred bandicoots, which are classified as threatened species and are
      vulnerable to extinction.

PMID- 21862132
TI  - Willingness to pay for improvements in chronic long-acting insulin therapy in
      individuals with type 1 or type 2 diabetes mellitus.
AB  - BACKGROUND: Long-acting insulin treatments with varying clinical benefits are
      currently available for patients with type 1 diabetes mellitus (T1DM) and type 2
      diabetes mellitus (T2DM). The current evidence base demonstrates the efficacy of
      treatments, but it is critical also to understand patient preferences regarding
      treatments and how they are determined. OBJECTIVE: This study aimed to measure
      the willingness to pay (WTP) of individuals with diabetes in the United Kingdom
      for different attributes of long-acting insulin therapy. METHODS: A survey based
      on discrete choice experiment methodology was developed to elicit the preferences
      and values of adults with T1DM or insulin-dependent T2DM regarding different
      aspects of their therapy. Participants were presented with a series of 27 paired
      choices and asked which they preferred. WTP values were calculated for relevant
      attribute levels. RESULTS: A total of 252 participants completed the
      questionnaire (52% response rate); 143 had T1DM and 109 had insulin-treated T2DM.
      The highest WTP values in participants with T1DM were avoiding 2-kg or 4-kg
      weight gain (L29 and L58, respectively), avoiding major difficulties with the
      injection device (L49), increasing the number of days per week when blood glucose
      levels are in the target range from 2 to 6 (L40), reducing the number of daily
      injections from 3 to 1 (L39), and avoiding nighttime hypoglycemia (L33). In
      participants with T2DM, similar factors had the highest WTP. CONCLUSIONS: This is
      the first study to assess WTP for long-acting insulin therapy and could have
      implications for future guidelines on diabetes management, however some
      limitations, notably in sample selection, could affect generalizability of the
      results. In both T1DM and T2DM, the highest WTP values were for avoidance of
      weight gain, and reduction in the number of injections and hypoglycemia.

PMID- 21862133
TI  - Remediation of water pollution caused by pharmaceutical residues based on
      electrochemical separation and degradation technologies: a review.
AB  - In the last years, the decontamination and disinfection of waters by means of
      direct or integrated electrochemical processes are being considered as a very
      appealing alternative due to the significant improvement of the electrode
      materials and the coupling with low-cost renewable energy sources. Many
      electrochemical technologies are currently available for the remediation of
      waters contaminated by refractory organic pollutants such as pharmaceutical
      micropollutants, whose presence in the environment has become a matter of major
      concern. Recent reviews have focused on the removal of pharmaceutical residues
      upon the application of other important methods like ozonation and advanced
      oxidation processes. Here, we present an overview on the electrochemical methods
      devised for the treatment of pharmaceutical residues from both, synthetic
      solutions and real pharmaceutical wastewaters. Electrochemical separation
      technologies such as membrane technologies, electrocoagulation and internal micro
      electrolysis, which only isolate the pollutants from water, are firstly
      introduced. The fundamentals and experimental set-ups involved in technologies
      that allow the degradation of pharmaceuticals, like anodic oxidation, electro
      oxidation with active chlorine, electro-Fenton, photoelectro-Fenton and
      photoelectrocatalysis among others, are further discussed. Progress on the
      promising solar photoelectro-Fenton process devised and further developed in our
      laboratory is especially highlighted and documented. The abatement of total
      organic carbon or reduction of chemical oxygen demand from contaminated waters
      allows the comparison between the different methods and materials. The routes for
      the degradation of the some pharmaceuticals are also presented.

PMID- 21862134
TI  - Emerging and historical brominated flame retardants in peregrine falcon (Falco
      peregrinus) eggs from Canada and Spain.
AB  - Comparisons of brominated flame retardants (BFRs) in the eggs of peregrine
      falcons (Falco peregrinus) recently collected (2003-2007), are made between
      Canada (N=12) and Spain (N=13). Overall, concentrations of sum (Sigma)
      polybrominated diphenyl ethers (PBDEs; 16 di-deca-BDE congeners) exceeded
      Sigmahexabromocyclododecane (HBCD) and were an order of magnitude higher than
      2,2'4,4',5,5'-hexabromobiphenyl (BB-153)>hexachlorocyclopentenyl
      dibromocyclooctane (HCBDCO)>1,2-bis(2,4,6-tribromophenoxy)ethane
      (BTBPE)>decabromodiphenylethane (DBDPE)>octabromotrimethylphenyllindane
      (OBIND)>hexabromobenzene (HBB)>bis(2-ethyl-1hexyl)tetrabromophthalate (BEHTBP).
      This is the first report of detectable HBCDCO and BEHTBP concentrations in biota,
      and the highest in ovo concentration of ?HBCD (14,617 ng/glw; Montreal, Canada)
      to date. There were significantly greater egg concentrations of BB-153,
      SigmaHBCD, and SigmaPBDE including BDE-153, -99, -100 and -183, in Canadian than
      Spanish peregrines with a terrestrial diet. HBB, BTBPE, and OBIND were detected
      in eggs from both countries, but only Canadian peregrine eggs had detectable
      levels of HCDBCO (25%) and DBDPE (N=1). The in ovo PBDE congener profile was
      dominated by BDE-153>BDE-99>BDE-47>BDE-183>BDE-100>BDE-209, with the isomeric
      HBCD pattern being alpha-HBCD>gamma-HBCD (beta-HBCD undetected). The Canadian
      peregrine eggs had lower enantiomeric HBCD values consistent with their higher
      fractions of (-) alpha-HBCD, suggesting selective enantiomeric enrichment or that
      the (+) alpha-isomer is more readily metabolized and so deposited in the egg
      through maternal transfer. Continental differences in egg burdens of peregrines
      are discussed relative to BFR usage patterns and exposure of peregrines on their
      breeding grounds.

PMID- 21862135
TI  - Opacification of intraocular lenses implanted during infancy: a clinicopathologic
      study of 4 explanted intraocular lenses.
AB  - OBJECTIVE: To report the clinicopathologic features of 4 opacified, single-piece,
      hydrophilic, acrylic intraocular lenses (IOLs) explanted from children who had
      undergone IOL implantation during infancy. DESIGN: Observational case series.
      PARTICIPANTS: Four IOLs explanted from 4 eyes of 3 children for visually
      significant opacification were included in the study. METHODS: The clinical
      details of each case were obtained to look for possible risk factors for IOL
      opacification. The explanted IOLs were subjected to gross examination, staining
      by alizarin red 1% for calcium, scanning electron microscopy, and energy
      dispersive x-ray spectroscopy (EDS). Levels of calcium and phosphorous were
      analyzed in the serum of all cases and in the aqueous humor of 1 case. MAIN
      OUTCOME MEASURES: Morphologic features and composition of deposits. RESULTS: Two
      cases had congenital cataract while one case was after bilateral lens sparing
      vitrectomy for retinopathy of prematurity. All underwent surgery during infancy
      with implantation of an IOL. The IOLs were explanted 8 months after surgery from
      4 eyes of 3 children at the age of 17, 25, and 26. All the children received a
      single-piece hydrophilic acrylic IOL. The IOLs were in situ for an average
      duration of 13.86 months. The deposits were in the shape of a bicycle wheel on 3
      IOLs and looked like fish eggs on 1 IOL. All deposits stained bright orange with
      alizarin red. On EDS, the deposits were found to be composed of calcium,
      phosphate, and silicone. CONCLUSIONS: The morphologic features and composition of
      IOL deposits in 2 cases were similar to those of earlier reports in adults. The
      hydrophilic nature of the IOL material, sulcus implantation, and postoperative
      inflammation may be possible risk factors for opacification. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 21862137
TI  - White matter changes in late-life depression: a diffusion tensor imaging study.
AB  - BACKGROUND: Numerous studies have revealed white matter abnormalities in late
      life depression (LLD). The objective was to investigate the integrity of white
      matter tracts in subjects with LLD compared to similar aged healthy individuals
      using diffusion tensor imaging (DTI). METHODS: Sixty eight subjects (30 healthy
      individuals, 38 depressed) underwent DTI on a 3T scanner following clinical and
      cognitive assessment. An automated tract-based spatial statistics (TBSS) method
      was used to derive estimates of fractional anisotropy (FA) and mean diffusivity
      (MD) for each subject. Group effects and correlations with clinical features on
      DTI parameters were examined. RESULTS: Compared to controls, uncorrected maps
      revealed patients with LLD exhibited lower FA in frontal, temporal and midbrain
      regions relative to older healthy subjects (p<0.05). However, using corrected
      maps no significant differences were observed in LLD patients in FA and MD
      parameters (p<0.05, family-wise error corrected for multiple comparisons).
      Regression analyses revealed no significant relationship between DTI parameters
      and current depressive symptoms in LLD (p>0.05, uncorrected and corrected).
      CONCLUSIONS: Findings are suggestive of loss of integrity in white matter fibres
      within frontal, temporal and midbrain regions, increasing the evidence that
      implicates disruptions to the limbic-orbitofrontal networks in the pathogenesis
      of LLD. However, as results did not survive strict control for multiple
      comparisons, they should be considered tentative and replication in larger
      cohorts is needed.

PMID- 21862136
TI  - Maternal posttraumatic stress symptoms and infant emotional reactivity and
      emotion regulation.
AB  - The current study examined associations between maternal posttraumatic stress
      disorder (PTSD) symptoms and infant emotional reactivity and emotion regulation
      during the first year of life in a primarily low-income, urban, ethnic/racial
      minority sample of 52 mother-infant dyads. Mothers completed questionnaires
      assessing their own trauma exposure history and current PTSD and depressive
      symptoms and their infants' temperament when the infants were 6 months old. Dyads
      participated in the repeated Still-Face Paradigm (SFP-R) when the infants were 6
      months old, and infant affective states were coded for each SFP-R episode.
      Mothers completed questionnaires assessing infant trauma exposure history and
      infant current emotional and behavioral symptoms when the infants were 13 months
      old. Maternal PTSD symptoms predicted infants' emotion regulation at 6 months as
      assessed by (a) infant ability to recover from distress during the SFP-R and (b)
      maternal report of infant rate of recovery from distress/arousal in daily life.
      Maternal PTSD symptoms also predicted maternal report of infant externalizing,
      internalizing, and dysregulation symptoms at 13 months. Maternal PTSD was not
      associated with measures of infant emotional reactivity. Neither maternal
      depressive symptoms nor infant direct exposure to trauma accounted for the
      associations between maternal PTSD symptoms and infant outcomes. These findings
      suggest that maternal PTSD is associated with offspring emotion regulation
      difficulties as early as infancy. Such difficulties may contribute to increased
      risk of mental health problems among children of mothers with PTSD.

PMID- 21862138
TI  - A randomized, single-blind, comparison of duloxetine with bupropion in the
      treatment of SSRI-resistant major depression.
AB  - INTRODUCTION: For patients who continue to experience depressive symptoms despite
      an adequate antidepressant SSRI trial, across-class switch is considered one of
      the best treatment options. The goal of the present work was to compare in terms
      of efficacy two different dual-action compounds, duloxetine and bupropion, in
      patients who failed to respond in two consecutive antidepressant trials with
      SSRIs. METHODS: The patients were allocated randomly to duloxetine (120 mg daily)
      or bupropion extended release (300 mg daily). The intended medication period was
      6 weeks. The primary measure of efficacy was depressive symptoms severity.
      RESULTS: A total of 49 participants were randomly assigned to duloxetine 120 mg
      (n=27) or bupropion 300 mg (n=22). The ITT efficacy patient sample consisted of
      46 patients. Relatively high response and remission rates in treatment groups
      were found: from 60 to 70% of patients responded to treatment, and approximately
      30 to 40% were in remission by the endpoint (week 6). No statistically
      significant difference emerged between the two groups at any post-baseline
      assessment, neither on mean scores of rating scales nor on qualitative efficacy
      measures. LIMITS: Limitations of the study are the lack of a placebo arm,
      difficult to include owing to ethical reasons, and the relatively small size of
      the sample. CONCLUSIONS: These preliminary results seem to support the hypothesis
      that in patients unresponsive to SSRIs the administration of antidepressants with
      different mechanisms of action is an effective switching strategy. Further
      studies are needed in light of the challenge posed by resistant depression.

PMID- 21862139
TI  - Genomic survey of polymorphisms in pattern recognition receptors and their
      possible relationship to infections in pigs.
AB  - Recent progress in the accumulation of pig genomic information has enabled us to
      comprehensively explore polymorphisms in pig genes. One of our targets for
      exploration has been the genes encoding molecules related to pathogen
      recognition, such as pattern recognition receptors (PRRs). PRRs play a role in
      the innate immune system, and possess various members such as Toll-like receptors
      (TLRs), NOD-like receptors (NLRs), RIG-like helicases (RLHs), and C-type lectin
      like receptors (CLRs). PRRs are required for the monitoring of pathogens;
      therefore, polymorphisms in PRRs may influence molecular functions such as ligand
      recognition. There have been many studies on the relationship between
      polymorphisms within PRR genes and disease susceptibility in humans and mice. Our
      studies have revealed that porcine PRR genes possess many nonsynonymous
      polymorphisms, particularly in regions encoding the ectodomains of TLRs localized
      on the cell surface. The genes encoding TLRs located on the membrane of
      intracellular compartments, and cytoplasmic PRRs such as NLRs and RLHs, also
      possessed nonsynonymous polymorphisms. Several observations indicate that there
      are relationships between polymorphisms in PRR or related genes and disease
      susceptibility in livestock animals including pig. Such information may
      contribute to breeding aimed at disease resistance, and effective vaccine design.

PMID- 21862140
TI  - Depression in hearing-impaired children.
AB  - OBJECTIVE: The purpose of this study was to examine the levels of depressive
      symptoms and the unique contribution of two aspects of emotion regulation (coping
      and mood states) to the development of depression in hearing-impaired children
      and a control group. METHODS: In order to compare the groups, self-report
      questionnaires concerning symptoms of depression, coping strategies, and mood
      states were used. The study group consisted of 27 children with cochlear
      implants, 56 children with conventional hearing aids, and 117 normally hearing
      children. RESULTS: Hearing-impaired children reliably reported more symptoms of
      depression than their normally hearing peers. Degree of hearing loss,
      socioeconomic status, gender, and age were unrelated to the level of depressive
      symptoms. But attending mainstream schools or using exclusively speech for
      communication were related to fewer depressive symptoms. The associations with
      depressive symptoms differed between the groups. For hearing-impaired children,
      the cognitive aspects (coping) and the affective aspects (mood states) of
      emotional functioning contributed separately to the prediction of depressive
      symptoms. For normally hearing children an integration of cognitive and affective
      aspects was detected: adequate coping skills prevented the development of
      negative mood states and in turn depressive symptoms. CONCLUSIONS: Hearing
      impaired children reported more depressive symptoms than normally hearing
      children. Prevention and treatment of depression in hearing-impaired children
      could focus on the use of coping strategies adequately, because these strategies
      have a direct relation with the level of depression.

PMID- 21862141
TI  - Systems genetics for drug target discovery.
AB  - The collection and analysis of genomic data has the potential to reveal novel
      druggable targets by providing insight into the genetic basis of disease.
      However, the number of drugs targeting new molecular entities, approved by the US
      Food and Drug Administration has not increased in the years since the collection
      of genomic data has become commonplace. The paucity of translatable results can
      be partly attributed to conventional analysis methods that test one gene at a
      time in an effort to identify disease-associated factors as candidate drug
      targets. By disengaging genetic factors from their position within the genetic
      regulatory system, much of the information stored within the genomic data set is
      lost. Here we discuss how genomic data is used to identify disease-associated
      genes or genomic regions, how disease-associated regions are validated as
      functional targets, and the role network analysis can play in bridging the gap
      between data generation and effective drug target identification.

PMID- 21862142
TI  - MicroRNAs and their potential involvement in HIV infection.
AB  - Treatment and cure of HIV-1 infection remain one of the greatest therapeutic
      challenges owing to its persistent infection, which often leads to AIDS. Although
      it has been 28 years since the discovery of the virus, the development of an
      effective vaccine is still years away. Relatively newly discovered miRNAs are a
      family of small noncoding RNAs that can regulate gene expression primarily by
      binding to the 3' untranslated region of targeted transcripts. An understanding
      of how HIV-1 infection affects the host miRNA pathway could generate new insights
      into the basic mechanisms underlying HIV-1-mediated pathologies and T-lymphocyte
      depletion. Here, we review literature on the biogenesis of HIV-1-encoded miRNAs,
      cellular miRNAs that can directly target HIV-1 or essential cellular factors
      required for HIV-1 replication. We also discuss the feasibility of using miRNAs
      for HIV-1 therapy.

PMID- 21862144
TI  - Obstructive sleep apnea syndrome (OSAS) and social support in elder patients.
AB  - Social support is a very important aspect in debilitating diseases. OSAS is a
      disabling disease that impairs social functioning and accounts for a large socio
      economic burden for the community. In this study our aim is to investigate social
      support levels among OSAS patients: 85 of them with the diagnosis of OSAS were
      enrolled in the study. Multidimensional scale of perceived social support (MSPSS)
      is used to measure the perception of individuals' social support sufficiency. In
      contrast to many studies, we found that social support levels of elder patients
      were higher than the young ones and family subscale was significantly higher. It
      might be both due to Turkish family structure that the grands are in close
      relationship with the other family members and the adverse effects of the disease
      which have more negative impact on young patients' life. In conclusion, social
      support is an important aspect in OSAS patients. The interventions for the
      enhancement of social support could lead to substantial cost-savings, reduce
      morbidity, and increase well-being.

PMID- 21862143
TI  - Risk factors for falls and fall-related injuries in adults 85 years of age and
      older.
AB  - Falls are a leading cause of morbidity and mortality in older adults. No previous
      studies on risk factors for falls have focused on adults 85 years and older, the
      most rapidly growing segment of adults. We examined demographic, health, and
      behavioral risk factors for falls and fall-related injuries in adults 65 years
      and older, with a particular focus on adults 85 years and older. We analyzed self
      reported information from the Behavioral Risk Factor Surveillance System (BRFSS)
      for 2008. Data was available for 120,923 people aged 65 or older and 12,684
      people aged 85 or older. Of those aged 85 or older, 21.3% reported at least one
      fall in the past 3 months and 7.2% reported at least one fall related injury
      requiring medical care or limiting activity for a day or longer. Below average
      general health, male sex, perceived insufficient sleep, health problems requiring
      assistive devices, alcohol consumption, increasing body mass index and history of
      stroke were all independently associated with a greater risk of falls or fall
      related injuries. The greater risk of falling in those 85 years and older
      appeared to be due to the deterioration of overall health status with age; among
      those with excellent overall health status, there was no greater risk of falling
      in adults 85 years and older compared to those 65-84 years of age. Our results
      suggest that those with risk factors for falls and fall-related injuries may be
      appropriate targets for evidence-based fall prevention programs.

PMID- 21862145
TI  - Health and nursing problems of elderly patients related to bio-psycho-social need
      deficiencies and functional assessment.
AB  - Elderly population is characterized by larger need for social welfare and medical
      treatment than other age groups. Along with aging, there is a number of emerging
      health, nursing, caring, psychological and social problems. Complexity of these
      problems results from overlapping and advancing involutional changes, multi
      illness, decreased functional efficiency and other factors. The aim of the study
      was the assessment of health problems in geriatric patients as well as bio-psycho
      social need deficiencies in a view of selected parameters of functional
      efficiency. The research group consisted of the Chair and Clinic of Geriatrics,
      186 women and 114 men, 300 persons in total. The research was carried out using a
      diagnostic poll method with the application of the Activities of Daily Living
      (ADL) questionnaire of assessment of daily efficiency on the basis of the Katz
      Scale; the Care Dependency Scale (CDS) questionnaire used to measure the level of
      the care dependency and human needs, Norton's bed sores risk assessment scale,
      the Nursing Care Category (NCC) questionnaire applied to assess the need for
      nursing care. In most patients the results unveiled manifestations of three or
      more illnesses. Functional efficiency was at low and average level. Half of the
      subjects were endangered by risk of bed sores as well as showed high need
      fulfillment deficiency. The highest level of the deficiency was observed in
      patients in the eldest age group as well as suffering from multi-illness.
      Material status, education, place of residence or gender showed no significant
      influence on the level of need fulfillment.

PMID- 21862147
TI  - Interrater reliability of the interRAI Acute Care (interRAI AC).
AB  - We examined the interrater reliability of the interRAI AC. An observational study
      was conducted on 3 geriatric wards. Two trained raters completed independently
      the interRAI AC between 24 and 48 h after admission. A sample of 100 patients
      (age 84.5 +/- 5.6 years; 45% female) was analyzed. Interrater reliability was
      tested using observed agreement, kappa coefficients, and intraclass correlation
      coefficients. The overall kappa median value for nominal items was 0.82 (almost
      perfect). For items on ordinal level, both the overall weighted kappa median and
      the intraclass correlation coefficient median were 0.86 (almost perfect).
      According to conventional cut-offs for interpreting kappa statistics, reliability
      was almost perfect (K >= 0.81) for 60% of all items, substantial (0.60 < K <=
      0.80) for 26%, moderate (0.41 < K <= 0.60) for 10%, and poor (K <= 0.40) for 4%
      of the items. The median observed agreement was 0.89. For 83% of the items, the
      observed agreement was greater than 0.80. This study showed substantial or almost
      perfect interrater reliability for 86% of the items. In addition to previous
      evidence, the current results suggest that the estimates of the interrater
      reliability of the interRAI AC are acceptable and provide preliminary evidence
      that the current version is appropriate for clinical application.

PMID- 21862146
TI  - Optimal cut points of waist circumference (WC) and visceral fat area (VFA)
      predicting for metabolic syndrome (MetS) in elderly population in the Korean
      Longitudinal Study on Health and Aging (KLoSHA).
AB  - Optimal cut points of central obesity identifying subjects at risk for MetS were
      proposed ethnic-specifically, but have not been established yet. Of particular
      interest are the values for elderly persons, which have not been identified
      previously. We investigated the appropriate cut points of WC and VFA for elderly
      in a community-based cohort in Korea. We recruited 294 men and 313 women aged 65
      or over who participated in the KLoSHA. A receiver operating characteristic (ROC)
      curve analysis was used to estimate the optimal cut points of WC and VFA
      indicative of MetS. The optimal cut points for predicting MetS were 87 cm for WC,
      140 cm(2) for VFA in men, and 85 cm for WC, 100 cm(2) for VFA in women with the
      Youden index. Similar cut points were obtained with the closest-to-(0, 1)
      criterion except for VFA in men, which was 122 cm(2). When adjusted for age,
      exercise, smoking, and alcohol consumption, men with >=122 cm(2) and women with
      >=100 cm(2) of VFA had a higher risk of MetS than subjects with lower values. The
      cut points of VFA and WC at risk for MetS were higher in men than women. In this
      community-based elderly cohort, the optimal cut points of WC at risk for MetS
      were lower than the Western criteria. Compared with the cut points in middle-aged
      Koreans, the cut points for elderly were lower in men and similar in women.

PMID- 21862148
TI  - Transient loss of consciousness in young adults.

PMID- 21862149
TI  - Predictors of outcome of non-ischemic mitral valve surgery.
AB  - BACKGROUND: Data on the risk stratification of patients undergoing mitral valve
      (MV) surgery for non-ischemic mitral disease are sparse. The present study seeks
      to define them in a contemporary cohort. METHODS: 193 consecutive patients
      referred to non-ischemic MV surgery were prospectively studied. Baseline
      characteristics and the type of surgery were analyzed with regard to operative
      and late mortality as well as functional outcome. RESULTS: 129 patients underwent
      MV replacement and 64 MV repair. MV replacement patients presented with more
      symptoms (p = 0.010), higher EuroSCORE (6.1 versus 5.6; p=0.009), more frequently
      underwent additional valve surgery (7.8 versus 0%; p = 0.003) and were more
      frequently female (p=0.048). Operative mortality was 3.1%, two thirds of
      operative deaths had additional surgery of the tricuspid valve (p = 0.019).
      Patients were followed for 5.2 +/- 2.7 years. 1-, 3-, 5- and 7-year survival
      rates were 93-, 91-, 82-, and 79% in MV replacement patients versus 100-, 98-, 96
      , and 89% in patients with MV repair (p = 0.015). However, by multivariate
      logistic regression, overall mortality was determined by additional surgery of
      the tricuspid valve (p = 0.0103), multivessel coronary disease (p = 0.026), and
      age (p<0.0001), but not by the type of surgery (p=0.066). Furthermore, the type
      of surgery did not influence functional outcome (p = 0.515). CONCLUSIONS: Apart
      from age and coronary artery disease the need for additional tricuspid valve
      surgery significantly determines the outcome of non-ischemic MV surgery. The type
      of operation appears less important when the need for additional valve surgery
      and co-morbidities like coronary artery disease are taken into consideration.

PMID- 21862150
TI  - Outcomes of patients with chronic kidney disease and implantable cardiac
      defibrillator: primary versus secondary prevention.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with worse survival in
      patients with implantable cardiac defibrillators (ICDs). This study examined the
      association of outcomes with CKD in patients receiving an ICD for primary versus
      secondary prevention. METHODS: The study included 696 patients who underwent ICD
      placement for clinical reasons (59% primary, 41% secondary prevention) at the
      University of Alabama at Birmingham between January 2002 and September 2007. CKD
      was defined as an estimated glomerular filtration rate<60 ml/min/1.73 m(2) but
      not on dialysis. Outcomes of interest included overall mortality and first
      appropriate ICD therapy (shocks or anti-tachycardia pacing). RESULTS: After a
      follow-up of 50 +/- 24 months, 213 patients died (31%) and 111 (16%) received
      appropriate ICD therapy. Patients with CKD had higher mortality than patients
      with no CKD in the primary (43% vs. 15%, p<0.001) and secondary prevention (37%
      vs. 23%, p = 0.003) groups. Patients with CKD were at higher risk of receiving an
      appropriate ICD therapy than patients without CKD in the primary (p<0.001) but
      not secondary prevention (p = 0.9) cohort. After adjusting for age, gender and
      multiple risk factors, CKD was independently associated with all-cause mortality
      and ICD therapy in the primary prevention group (HR 2.08 [1.34-3.23] and 3.53
      [1.75-7.10], p = 0.001 and <0.0001, respectively) but not in the secondary
      prevention group (HR 1.27 [0.81-2.00], and 0.63 [0.35-1.13], p=0.3 and 0.2,
      respectively). CONCLUSIONS: CKD is independently associated with increased
      mortality and appropriate ICD therapy in patients undergoing ICD implantation for
      primary but not secondary prevention.

PMID- 21862151
TI  - Early recurrence of atrial fibrillation as a predictor for 1-year efficacy after
      successful phased RF pulmonary vein isolation: evaluation of complaints and
      multiple Holter recordings.
AB  - BACKGROUND: Early arrhythmia recurrences after pulmonary vein isolation (PVI) for
      atrial fibrillation (AF) are accepted as part of the blanking period. Their
      relevance for long-term efficacy is not well-known. We evaluated patients, who
      came to hospital with a documented recurrence of AF, or had a registered episode
      of AF on the 24-hour Holter 6 weeks after PVI and compared it with long-term
      outcome. METHODS: One hundred consecutive patients with paroxysmal AF were
      treated with the PVAC. In the 3-month blanking period patients who came to
      hospital with a documented recurrence of AF on ECG were recorded. 6 weeks after
      procedure a 24-hour Holter was performed. After 3 months patients were asked if
      they felt a relapse. Follow-up was performed at 3, 6, and 12 months with ECG, 7
      day Holter at 6 and/or 12 months, and event recording if needed. RESULTS: Within
      the blanking period, 25/100 (25%) patients had a documented recurrence of AF
      while 46/100 (46%) patients felt a relapse. After the blanking period up to 12
      months, 53/100 (53%) patients were free of AF without anti-arrhythmic drugs.
      Multivariate regression analyses revealed that absence of AF in the blanking
      period (OR 0.22 95%CI [0.05-0.98]) and absence of a relapse of symptoms suspect
      for AF during the blanking period (OR 0.21 95%CI [0.06-0.52]) were independent
      predictors of successful long-term outcome. CONCLUSIONS: Poor long-term outcome
      is strongly related to patients who experienced palpitations with ECG documented
      AF, AF on the 24-hour Holter at 6 weeks after PVI and a relapse in the blanking
      period.

PMID- 21862152
TI  - Natural history of genotype positive-phenotype negative patients with
      hypertrophic cardiomyopathy.

PMID- 21862153
TI  - Accumulation of cardiovascular risks in Japanese women with abnormal glucose and
      mild to moderate hypercholesterolemia.

PMID- 21862154
TI  - C-reactive protein and endothelial dysfunction: gazing at the coronaries.

PMID- 21862155
TI  - Increased end diastolic wall stress precedes left ventricular hypertrophy in
      dilative heart failure--use of the volume-based wall stress index.
AB  - INTRODUCTION: To examine a potential interrelation of left ventricular (LV) wall
      stress and hypertrophy, we assessed increased wall stress in patients with
      suspected non-ischemic dilative cardiomyopathy and addressed the question whether
      increased LV wall stress is involved in the development of LV hypertrophy.
      METHODS: We studied 502 consecutive patients in whom LV mass, LV enddiastolic
      (LVEDV) and endsystolic volume (LVESV) was determined using cardiac magnetic
      resonance (CMR). Based on a thick-walled sphere, we introduced a myocardial and
      cavity volume-based wall stress index. Follow up CMR examinations were obtained
      in a representative subgroup of 71 patients. RESULTS: LV mass was correlated with
      LVEDV (r=0.517, P<0.001) and LVESV (r=0.510, P<0.001). Despite LV hypertrophy, LV
      mass was not sufficient to compensate for LV dilatation resulting in an increased
      wall stress. Increased LV enddiastolic wall stress was found in 227 patients (45
      %) and increased endsystolic wall stress in 198 (39 %). In patients with normal
      LV enddiastolic wall stress <= 4 kPa at time of enrolment, no changes of LV mass
      occurred during follow up (142 +/- 46 g vs. 141 +/- 47 g). In contrast, patients
      with initially increased LV enddiastolic wall stress >4 kPa developed greater LV
      hypertrophy (141 +/- 48 g vs. 158 +/- 60 g, P=0.0247). CONCLUSIONS: LV wall
      stress can be derived from CMR measurements of LV myocardium and cavity using the
      volume-based wall stress index. Increased LV enddiastolic wall stress leads to LV
      hypertrophy. Beyond a certain degree of LV dilatation, the extent of hypertrophy
      does not compensate LV dilatation. The ensuing increased wall stress promotes
      dilatation and consecutively hypertrophy with an unfavorable prognosis. It is
      proposed to use the volume-based wall stress index as new diagnostic criterion in
      heart failure.

PMID- 21862156
TI  - Aminoterminal natriuretic peptides and cardiovascular risk in an Italian male
      adult cohort.

PMID- 21862157
TI  - Cobalamin deficiency presenting as refractory vaso vagal syncope.

PMID- 21862158
TI  - Multidetector computed tomography vs multiplane transesophageal echocardiography
      in detecting atrial thrombi in patients candidate to radiofrequency ablation of
      atrial fibrillation.

PMID- 21862159
TI  - Hyperuricemia and increased risk of ischemic heart disease in a large Chinese
      cohort.
AB  - AIMS: There is an ongoing discussion on whether serum uric acid (SUA) predicts
      ischemic heart disease (IHD) independently of other metabolic factors, which, if
      confirmed, would signify a role for uric acid in the pathogenesis of
      cardiovascular disease. We investigated whether such a relation exists for ethnic
      Chinese with low CVD risk. METHODS AND RESULTS: Enrolled, between 1994 and 1996,
      were 128,569 adults >= 20 years from four 'MJ' Health Check-up Clinics in Taiwan.
      Excluded were those with heart disease, previous stroke(s), renal disease, and/or
      cancer. Physical examinations, biospecimen collections, and structured
      questionnaires were executed according to standardised protocols. We identified
      IHD events according to the ICD-9-CM codes 410-414 using hospitalisation records
      obtained from the National Health Insurance and the Death Certification Registry
      databases. The Cox proportional hazard model was used to estimate the hazard
      ratios (HRs) between SUA and IHD events. A total of 2049 subjects (1239 men, 810
      women) developed IHD from baseline to Dec. 31, 2002. Men had a higher IHD
      incidence than did women (2.84 vs. 1.61 1/1000 person-years; p < 0.0001). The
      risk-factor-adjusted HRs (95% confidence-interval [CI]) for hyperuricemiae (SUA
      >= 7.0/>= 6.0mg/dL) were 1.25 (1.11-1.40) for men and 1.19 (1.02-1.38) for women.
      In the low-risk population (lacking the NCEP-ATPIII metabolic syndrome
      components), a significant association was still observed (adjusted HR: 1.54
      [1.09-2.17]). CONCLUSION: The hyperuricemia was independently associated with the
      development of IHD not only in the general population but also in those without
      any metabolic risk factor for NCEP ATPIII. Hyperuricemia may be considered as a
      potential risk factor for IHD.

PMID- 21862160
TI  - Short QT syndrome presenting with atrial fibrillation and LV hypertrophy.

PMID- 21862161
TI  - A prospective study of supine versus prone positioning and whole-body
      thermoplastic mask fixation for craniospinal radiotherapy in adult patients.
AB  - PURPOSE: To evaluate neuroaxis irradiation for adults in the supine position
      using head body thermoplastic mask fixation, from the aspects of dose
      distribution, patient comfort and set-up accuracy. METHODS AND MATERIALS: Nine of
      the 12 adult patients were positioned for craniospinal axis irradiation in both
      prone and supine positions. After mask fixation and planning CTs in both
      positions, a questionnaire relating to the comfort was completed. The doses to
      the target and to the organs at risk of the 3D conformal plans in the supine and
      prone positions were compared. Portal images of all 12 patients irradiated in the
      supine position were evaluated, the van Herk formulas being used to calculate the
      systemic and random errors. RESULTS: No significant difference was found between
      the prone and supine positions target coverage, the dose homogeneity and the dose
      to the organs at risk. The supine position was considered more comfortable by the
      patients (scores of 2.8 versus 4.29), with a vector random error of 3.27 mm, and
      a systematic error of 0.32 mm. The largest random set-up error was observed in
      the lateral direction: 4.83 mm. CONCLUSIONS: The more comfortable supine position
      is recommended for craniospinal irradiation in adult patients. Whole-body
      thermoplastic mask immobilization provides excellent repositioning accuracy.

PMID- 21862162
TI  - External loading and maximum dynamic output in vertical jumping: the role of
      training history.
AB  - We examined the effect of training history on the load-power relationship in
      vertical jumping (VJ) by employing external loads ranging from -30% to +30% body
      weight (BW). Based on previous findings, we hypothesized that (1) the maximum
      dynamic output (power production and momentum generation) would be within the
      tested loading interval, and (2) the load-power and load-momentum relations would
      depend on the subject's training history. Thirty-one healthy male subjects of
      different training history (i.e., 9 strength-trained athletes, 12 speed-trained
      athletes, and 10 sedentary individuals), performed maximum countermovement jumps
      on a force plate while a pulley system was used to either reduce or increase the
      subject's BW. An increase in external loading during VJ resulted in a systematic
      decrease (p<.001) in power production and momentum generation in all 3 studied
      groups. We also observed significant Group*Load interactions (p<.01) for the load
      power and the load-momentum relationships, probably due to the group differences
      in slopes of the trend lines that describe the loading-associated changes in
      power and momentum. The results suggest that, from the evolutionary standpoint,
      the human muscular system of the lower limbs could be designed to produce the
      maximum power output against the loads that are well below the mass and inertia
      of the human body.

PMID- 21862163
TI  - Effects of shearing and fleece cleanliness on microbiological contamination of
      lamb carcasses.
AB  - The meat industry in Norway has developed national guidelines for Good Hygiene
      Practices for slaughtering and skinning, based on categorisation of animals.
      These include shearing sheep and lambs in the abattoirs immediately before
      slaughter. The aim of this study was to investigate microbiological carcass
      contamination associated with: (i) different shearing regimes; (ii) fleece
      cleanliness; and (iii) the slaughter process. In addition, the efficacy of the
      national guidelines in reducing microbial contamination was evaluated. A total of
      280 swab samples were collected from the brisket areas (100 cm(2)) of 140
      naturally contaminated lamb carcasses in a commercial abattoir. Half the samples
      were collected at skinning of brisket areas at the start of the slaughter-line
      and half of them were collected at the end of slaughter-line, just before
      chilling. The lambs were divided into four groups (n=35) according to the
      duration of the period between shearing and slaughter: (i) 0 days (shorn at the
      abattoir immediately before slaughter); (ii) three days; (iii) seven days; and
      (iv) not shorn. Mean log colony forming units (CFU) per 100 cm(2) at skinning
      were 5.78 and 6.95 for aerobic plate count (APC) (P<0.05), 1.65 and 2.78 for
      Escherichia coli (P<0.05) for shorn and unshorn lambs, respectively. For shorn
      lambs, divided according to the period between shearing and slaughter, the mean
      log CFU per 100 cm(2) were 5.45, 5.75, 6.12 (APC) and 1.77, 1.46, 1.71 (E. coli)
      for the 0-days, 3-days and 7-days groups, respectively (P<0.05 for the difference
      between 0- and 7-days groups in APC results). A four-category scale (0-3) was
      used for assessing fleece cleanliness before skinning. Visually clean lambs
      (score '0') had lower levels of APC on the carcass surfaces than those
      categorised as dirty (score '2-3') (P<0.05). The carcasses at the end of the
      slaughter-line had lower levels of APC than they had at skinning. However, the
      statistical significant reduction of E. coli on carcass surfaces at skinning
      point for shorn lambs, were impaired and no longer significantly different from
      the unshorn group at the end of the slaughter-line. The increased E. coli level
      at the end of the slaughter-line might be explained by weaknesses related to
      slaughter hygiene in particular suboptimal evisceration in the abattoir which was
      used as a basis for our trial, and thus the national guidelines concerning
      shearing had not the fully intended effect on reducing microbial carcass
      contamination.

PMID- 21862164
TI  - Microbiological and chemical characterisation of ting, a sorghum-based sourdough
      product from Botswana.
AB  - Ting is a fermented sorghum product of Botswana which is used to prepare
      porridges of different consistencies. This study aimed to characterise ting with
      respect to fermentation microbiota and metabolite composition, and to develop
      starter cultures for ting fermentation. The pH values of 10 ting samples from
      Botswana ranged between 3.5 and 4.0 and cell counts ranged between 1.2*10(8) and
      1.2*10(10)cfu/g lactic acid bacteria. Yeast cell counts were below 10(5)cfu/g in
      all samples and Enterobacteriaceae were less than 10 cfu/g. The microbiota of
      samples consisted of 2-4 dominant strains and strains were identified based on
      the sequence of their 16S rRNA genes as Lactobacillus reuteri, Lactobacillus
      fermentum, Lactobacillus harbinensis, Lactobacillus plantarum, Lactobacillus
      parabuchneri, Lactobacillus casei and Lactobacillus coryniformis. Binary strain
      combinations were employed as starter cultures to produce ting. Major
      fermentation products were lactate, acetate and ethanol, additionally, 1,2
      propanediol and 1,3 propanediol were produced by some strains. All strains were
      capable of producing ting, which was accompanied by a decrease in pH from 6.3 to
      4 within 8h. Traditionally processed ting requires 2 to 3 days to attain a pH
      below 4; the starter cultures thus reduced the fermentation time to 8h.

PMID- 21862165
TI  - The relationship between self-monitoring of blood glucose results and glycated
      haemoglobin in type 2 diabetes: the fremantle diabetes study.
AB  - The benefits of self-monitoring of blood glucose (SMBG) in type 2 diabetes remain
      contentious. If SMBG data do not accurately reflect HbA(1c), attempts to modify
      lifestyle/pharmacotherapy will be ineffective. We aimed to determine how well
      SMBG correlates with HbA(1c) and fasting serum glucose (FSG). Community-based
      type 2 patients using SMBG provided their highest and lowest pre- and post
      prandial glucose results in the week before detailed assessment. The ability of
      average pre- and post-prandial SMBG to predict HbA(1c)>7.0% was determined by
      linear regression and receiver operating characteristic (ROC) analyses. Of 1286
      patients with known SMBG status, 70% reported using SMBG. Pre-prandial SMBG data
      were obtained from 554 participants and post-prandial SMBG data from 418. The
      mean SMBG result and HbA(1c) correlated significantly (pre-prandial r(s)=0.55,
      post-prandial r(s)=0.47; P<0.001). Areas under the ROC curve (95% confidence
      limits) were 0.78 (0.74-0.83) and 0.74 (0.69-0.78) for pre- and post-prandial
      SMBG (P<0.04). The optimal cut-point was 6.5 mmol/L for pre-prandial SMBG
      (sensitivity 79.3%, specificity 64.4%). Mean pre-prandial SMBG results correlated
      with FSG (r(s)=0.64, P<0.001) but were on average 1.4 mmol/L lower, consistent
      with known whole blood vs. plasma differences. Since SMBG values reflect
      prevailing glycaemia, refinements in their interpretation and application may
      improve SMBG effectiveness.

PMID- 21862166
TI  - Associations between the use of metformin, sulphonylureas, or diet alone and
      cardiovascular outcomes in 6005 people with type 2 diabetes in the FIELD study.
AB  - AIMS: We aimed to determine the associations between metformin or sulphonylurea
      monotherapy at study entry into the FIELD diabetes trial and (1) metabolic risk
      factors, (2) risk of a first major cardiovascular (CVD) outcome, and (3) the
      effect of each therapy on the risk-modifying effect of fenofibrate. METHODS:
      Patients receiving metformin or sulphonylureas without insulin therapy were
      compared for the relative risk of CVD outcomes, adjusted for differences in
      baseline characteristics likely to affect risk. RESULTS: Metformin-treated
      patients were likely to be younger, female, or obese. Metformin was associated
      with higher levels of lipids (other than LDL-C) and homocysteine (P<0.001).
      Sulphonylurea-treated patients had a longer history of diabetes and more CVD and
      microvascular disease. Sulphonylurea treatment was associated with higher plasma
      creatinine and lower plasma HDL-C (P<0.001). The risks of all CVD outcomes were
      higher for those on sulphonylureas than diet alone, but were nonsignificant after
      adjustment for the duration and intensity of diabetes and severity of risk
      factors. Metformin and sulphonylureas did not significantly influence the
      benefits of fenofibrate on CVD outcomes. CONCLUSIONS: Apparent differences in the
      risk of CVD outcomes associated with oral hypoglycemics therapy were largely
      abolished by adjustment for diabetes and CVD risk factors.

PMID- 21862167
TI  - Proteasome modulator 9 and carpal tunnel syndrome.
AB  - Proteasome modulator 9 (PSMD9) is linked to type 2 diabetes (T2D). The author
      studied whether PSMD9 IVS3 + nt460 A > G, IVS3 + nt437 T > C and E197 are linked
      to carpal tunnel syndrome in T2D Italian families. Non-parametric linkage,
      linkage disequilibrium-based and independent SNPs-based linkage analyses were
      performed. The PSMD9 SNPs show linkage to carpal tunnel syndrome.

PMID- 21862168
TI  - Serum sex hormone-binding globulin levels are independently associated with
      nonalcoholic fatty liver disease in people with type 2 diabetes.
AB  - AIM: To clarify the association between serum sex hormone-binding globulin (SHBG)
      levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2
      diabetes. METHODS: Two hundred seventy nine patients with type 2 diabetes were
      consecutively enrolled and metabolic parameters were checked. High-grade NAFLD
      was defined as moderate or severe fatty liver disease, measured using liver
      ultrasound. SHBG, testosterone, and estradiol levels were measured. RESULTS: SHBG
      levels were lower in patients with high-grade NAFLD than in those with normal
      ultrasound and decreased significantly based on the severity of fatty liver
      disease. SHBG levels were negatively correlated with hypertension, body mass
      index (BMI), waist circumference, high-grade NAFLD, triglycerides, alanine
      aminotransferase (ALT), gamma-glutamyltransferase (gammaGT), homeostasis model
      assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein (CRP)
      and were positively correlated with testosterone and estradiol levels. The odds
      ratios (ORs) predicting the presence of high-grade NAFLD in men and women
      decreased significantly with increasing SHBG tertile. The ORs remained
      significant even after further adjusting for BMI, waist circumference,
      hypertension, triglycerides, gammaGT, ALT, CRP, HOMA-IR, testosterone, estradiol,
      and anti-diabetic medications. CONCLUSIONS: Serum SHBG levels were independently
      associated with the high-grade NAFLD in patients with type 2 diabetes.

PMID- 21862169
TI  - fMRI analysis on the GPU-possibilities and challenges.
AB  - Functional magnetic resonance imaging (fMRI) makes it possible to non-invasively
      measure brain activity with high spatial resolution. There are however a number
      of issues that have to be addressed. One is the large amount of spatio-temporal
      data that needs to be processed. In addition to the statistical analysis itself,
      several preprocessing steps, such as slice timing correction and motion
      compensation, are normally applied. The high computational power of modern
      graphic cards has already successfully been used for MRI and fMRI. Going beyond
      the first published demonstration of GPU-based analysis of fMRI data, all the
      preprocessing steps and two statistical approaches, the general linear model
      (GLM) and canonical correlation analysis (CCA), have been implemented on a GPU.
      For an fMRI dataset of typical size (80 volumes with 64*64*22voxels), all the
      preprocessing takes about 0.5s on the GPU, compared to 5s with an optimized CPU
      implementation and 120s with the commonly used statistical parametric mapping
      (SPM) software. A random permutation test with 10,000 permutations, with
      smoothing in each permutation, takes about 50s if three GPUs are used, compared
      to 0.5-2.5h with an optimized CPU implementation. The presented work will save
      time for researchers and clinicians in their daily work and enables the use of
      more advanced analysis, such as non-parametric statistics, both for conventional
      fMRI and for real-time fMRI.

PMID- 21862170
TI  - The population ecology and social behaviour of taxonomists.

PMID- 21862171
TI  - The genetics of migration on the move.
AB  - Across a range of organisms, related species or even populations of the same
      species exhibit strikingly different scales and patterns of movement. A
      significant proportion of the phenotypic variance in migratory traits is genetic,
      but the genes involved in shaping these phenotypes are still unknown. Although
      recent achievements in genomics will evolve migratory genetics research from a
      phenotypic to a molecular approach, fully sequenced and annotated genomes of
      migratory species are still lacking. Consequently, many of the genes involved in
      migration are unavailable as candidates. Migration is central to the life-history
      adaptations of many animals. Here, we review current understanding of the genetic
      architecture of migratory traits and discuss the significant implications this
      will have for other areas of biology, including population responses to climate
      change, speciation and conservation management.

PMID- 21862173
TI  - What history reveals about reactions to climate debates.

PMID- 21862174
TI  - Calcium dependent protein kinase (CDPK) expression during fruit development in
      cultivated peanut (Arachis hypogaea) under Ca2+-sufficient and -deficient growth
      regimens.
AB  - Adequate soil calcium (Ca2+) levels are crucial for sustained reproductive
      development of peanut (Arachis hypogaea). A role for calcium dependent protein
      kinase was evaluated during peanut fruit development under sufficient and
      deficient soil Ca2+ conditions. Quantitative RT-PCR and protein gel blot analyses
      confirmed transcriptional upregulation of CDPK in seeds developing under
      inadequate soil Ca2+ regimen, as well as spatiotemporal regulation of CDPK
      expression during early mitotic growth and later during the storage phase of seed
      development. However, a consistent basal level of CDPK was present during similar
      developmental stages of pod tissue, irrespective of the soil Ca2+ status.
      Immunolocalization data showed CDPK decoration primarily in the outer most cell
      layers of the pericarp and around vascular bundles linked by lateral connections
      in developing pods, as well as the single vascular trace supplying nutrients to
      the developing seed. Finally, carbohydrate analyses and qRT-PCR data are provided
      for peanut genes encoding enzymes involved in sucrose cleavage (orthologs of
      Vicia faba, VfCWI1 and VfCWI2) and utilization (AhSuSy and AhSpS), and oleosin
      gene transcripts (AhOleo17.8 and AhOleo18.5) validating a role for CDPK in the
      establishment and maintenance of sink strength, and subsequent onset of storage
      product biosynthetic phase during seed maturation.

PMID- 21862175
TI  - Differences in endo/exogenous auxin profile in cuttings of different
      physiological ages.
AB  - The process of physiological ageing in woody plants is a very important factor
      influencing adventitious rooting. However, there is a lack of knowledge of
      biochemical backgrounds triggering ageing and consequently, rhizogenesis.
      Experiments with Prunus subhirtella 'Autumnalis' leafy cuttings of three
      different physiological ages (adult (over 40-year-old stock plants), semi-adult
      (5-year-old cutting plants) and juvenile (5-year-old in vitro plants)) were
      conducted in 2009. Half of the cuttings were banded ca. 3 cm above the bottom of
      the cutting with aluminum wire prior to insertion into the substrate to block the
      polar auxin transport. IBA, which was exogenously applied to the cuttings, could
      only be detected in the base of the cuttings on the first day after severance.
      Juvenile cuttings tended to have the highest values, but the effect was age
      specific. Later, the detection was not possible, regardless of the age. The IAA
      profile in cutting bases was similar for all physiological ages, reaching the
      peak on the first day after severance. Juvenile cuttings, in which the stems had
      been banded before insertion, contained more IAA in their bases on day 1 compared
      to the stems, which were not banded. These cuttings presumably transported
      absorbed auxin mainly via phloem, and not via mass flow like semi-adult and adult
      cuttings, where IAA concentrations were similar or even greater in non-banded
      cuttings compared to banded ones. These cuttings also tended to exhibit the best
      rooting results. The IAA-Asp accumulation was especially strong in adult
      cuttings, which contained significantly more aspartate on the first and third
      days after severance when compared with semi-adult and juvenile cuttings.

PMID- 21862176
TI  - Virucidal activity of different alcohols against murine norovirus, a surrogate of
      human norovirus.

PMID- 21862177
TI  - Assessment of temporal trends in mortality with implementation of a statewide ST
      segment elevation myocardial infarction (STEMI) regionalization program.
AB  - STUDY OBJECTIVE: Although regionalized care for ST-segment elevation myocardial
      infarction (STEMI) has improved the use of timely reperfusion therapy, its effect
      on patient outcomes has been difficult to assess. Our objective is to explore
      temporal trends in STEMI mortality with the implementation of a statewide STEMI
      regionalization program (Reperfusion of Acute Myocardial Infarction in North
      Carolina Emergency Departments [RACE]). METHODS: We compared trends in inpatient
      mortality among STEMI patients treated at North Carolina (NC) hospitals
      participating in the RACE program, relative to those not participating, using
      state inpatient claims data. Using Medicare claims data, we compared trends in 30
      day mortality among Medicare beneficiaries in NC with those nationally. Logistic
      models with random effects were used to evaluate the association of the program
      with mortality. RESULTS: From 2005 to 2007, inpatient mortality for 6,565 STEMI
      patients treated at NC hospitals participating in RACE decreased from 11.6% to
      10.1% (risk difference -1.5%; 95% confidence interval [CI] -3.0% to 0.04%),
      whereas inpatient mortality among 5,850 STEMI patients treated at NC
      nonparticipating hospitals decreased from 10.2% to 8.6% (risk difference -1.6%;
      95% CI -3.1% to 0.10%); (adjusted odds ratio 1.28; 95% CI 0.88 to 1.85 for
      temporal differences between groups). During the same period, 30-day STEMI
      mortality among Medicare beneficiaries decreased from 22.7% to 21.4% in NC (risk
      difference -1.28%; 95% CI -3.60% to 1.03%) and from 22.3% to 21.6% nationally
      (risk difference -0.71%, 95% CI -1.13% to -0.29%; adjusted odds ratio 0.99, 95%
      CI 0.85 to 1.15 for temporal differences between regions). CONCLUSION: The
      initiation of a statewide STEMI collaborative care model was associated with a
      reduction in mortality rates according to claims data, yet these changes were
      similar to those seen nationally. Further study is needed to evaluate
      regionalized systems of STEMI care and to determine the role of claims data to
      evaluate population-based STEMI outcomes.

PMID- 21862178
TI  - Extracorporeal albumin dialysis in three cases of acute calcium channel blocker
      poisoning with life-threatening refractory cardiogenic shock.
AB  - We describe 3 patients admitted to the medical-surgical ICU in a university
      hospital with life-threatening cardiogenic shock after the ingestion of high
      doses of calcium channel blockers (8.4 g sustained-release diltiazem, 4.2 g
      sustained-release diltiazem, and 14.4 g slow-release verapamil). Cardiovascular
      failure and cardiac conduction disturbances were unresponsive to the usual
      therapy (eg, intravenous injection of high doses of calcium, glucagon,
      hyperinsulinemia-euglycemia therapy, fluid resuscitation) and to increasing doses
      of simultaneous infusions of adrenergic agonists. Albumin dialysis with Molecular
      Adsorbents Recirculating System (MARS) therapy was performed because of its
      unique ability to selectively remove from circulation protein-bound toxins (and
      potentially drugs) that are not cleared by conventional hemodialysis. A single
      procedure was successfully performed in each patient, which was followed by rapid
      weaning of adrenergic agonist agents and full recovery of the life-threatening
      cardiovascular failure. At 2-year follow-up, patients were asymptomatic. Albumin
      dialysis with MARS therapy may be effective when used as a rescue procedure in
      patients presenting with sustained, life-threatening cardiogenic shock as a
      result of massive calcium channel blocker poisoning.

PMID- 21862180
TI  - [Cholangiopathy associated with portal hypertension].
AB  - Portal cholangiopathy encompasses a group of abnormalities of the biliary system
      and gallbladder that occur secondary to chronic portal vein thrombosis and
      collateral venous circulation. Chronic obstruction of the portal vein is a
      frequent cause of gastrointestinal variceal bleeding, but data on biliary tract
      abnormalities are limited. We report the case of a male patient with obstructive
      jaundice secondary to portal cholangiopathy. We describe the pathogenesis of this
      entity, and the various diagnostic and therapeutic options available.

PMID- 21862179
TI  - Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment.
AB  - Regional functional connectivity (FC) of 39 patients with Alzheimer's disease
      (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly
      controls was studied using resting-state functional magnetic resonance imaging
      (rs-fMRI). After a mean follow-up of 2.8 +/- 1.9 years, 7 MCI patients converted
      to AD, while 14 patients remained cognitively stable. Resting-state functional
      magnetic resonance imaging scans were analyzed using independent component
      analysis (ICA), followed by a "dual-regression" technique to create and compare
      subject-specific maps of each independent spatiotemporal component, correcting
      for age, sex, and gray matter atrophy. AD patients displayed lower FC within the
      default-mode network (DMN) in the precuneus and posterior cingulate cortex
      compared with controls, independent of cortical atrophy. Regional FC values of
      MCI patients were numerically in between AD patients and controls, but only the
      difference between AD and stable MCI patients was statistically significant.
      Correlation with cognitive dysfunction demonstrated the clinical relevance of FC
      changes within the DMN. In conclusion, clinically relevant decreased FC within
      the DMN was observed in AD.

PMID- 21862182
TI  - Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives.
      Part 1: perhydropyrrole[1,2-a]pyrazines.
AB  - A number of novel pyrrole[1,2-a]pyrazine derivatives were synthesized and
      evaluated in in vivo animal models of epilepsy. Among them, several compounds
      displayed promising seizure protection in the maximal electroshock seizure (MES),
      subcutaneous metrazol seizure (scMET), 6 Hz and pilocarpine-induced status
      prevention (PISP) tests, with ED(50) values comparable to the reference
      anticonvulsant drugs (AEDs). A critical influence of the stereochemistry and
      conformational preferences of the pyrrole[1,2-a]pyrazine core on in vivo
      pharmacological activity was observed. The mechanism of the anticonvulsant action
      of the agents synthesized is most probably not via inhibition of the voltage
      dependent sodium (Na(+)) currents.

PMID- 21862183
TI  - Synthesis and pharmacological evaluations of novel 2H-benzo[b][1,4]oxazin-3(4H)
      one derivatives as a new class of anti-cancer agents.
AB  - The synthesis of novel 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives has been
      carried out using trifluoroacetic anhydride/phosphoric acid mediated C-C bond
      forming reaction as a key step. This method does not require the use of
      environmentally harmful AlCl(3) or moisture sensitive acid chloride. A number of
      compounds containing the benzooxazinone moiety attached to a five-membered
      central heterocyclic ring was synthesized and tested for their anti-cancer
      properties in vitro against three cell lines e.g. A549 (lung), DLD-1 (colorectal
      adenocarcinoma) and MV4-11 (acute myeloid leukemia). Some of them showed anti
      cancer activities along with a number of reference compounds tested. Few of them
      showed promising anti-leukemic properties. A brief Structure-Activity
      Relationship study within the series is presented. An imidazole derivative 9c
      containing benzene ring with a para-CF(3) group at C-2 position was identified as
      a potent anti-leukemic agent.

PMID- 21862184
TI  - [Survey of general practitioners management of erysipelas].
AB  - PURPOSE: A few studies only have focused on ambulatory management of erysipelas.
      METHODS: To assess the diagnostic and therapeutic management of erysipelas by
      general practitioners, and their adherence to the French Society of Infectious
      Diseases and Dermatology joint 2000 recommendations, we surveyed 114 general
      practitioners during a 1 year period (from May 1st, 2005 to April 30th, 2006).
      RESULTS: Seventy-three general practitioners accepted to participate to the study
      and 54 cases of erysipelas were reported. Median age of patients was 63 years
      (range, 18-94) and sex ratio was 0.77. Lower limbs were affected in 83% out of
      the cases. A skin lesion was reported in 65% of the cases. None of the 15 doppler
      ultrasonography that were performed identified deep vein thrombosis. Five
      patients (9%) were initially hospitalized. Only 18% out of the patients were
      treated by amoxicillin. Most prescribed antimicrobial agents were pristinamycin
      (31%) and amoxicillin-clavulanate (27%). Median duration of treatment was 10
      days. Six patients received an anti-inflammatory drug. Among the 44 patients who
      had a follow-up visit, 37 patients (84%) recovered and two patients were
      hospitalized after this follow-up assessment. Two patients experienced a
      recurrence of erysipelas during the study. CONCLUSION: As previously reported in
      the literature, outcome of erysipelas after ambulatory management remains
      excellent, although recommendations are poorly followed.

PMID- 21862185
TI  - Depression in palliative care settings: the need for training for nurses and
      other health professionals to improve patients' pathways to care.
AB  - Depression is highly prevalent in patients receiving palliative care; however,
      detection rates are low, with many patients who suffer with depression continuing
      to go undetected and untreated. A number of factors unique to this setting, as
      well as issues relating to staff knowledge and self-efficacy working with
      depression, may impede the detection of patients who are depressed by
      professional health care staff. Although programmes aimed to train nurses and
      other allied health staff in depression may be an effective way to improve
      detection rates, there have been few studies investigating the efficacy of these
      interventions. This article draws upon recent literature to provide a narrative
      review of barriers to detection and factors relating to professional palliative
      care staffs' ability to provide pathways to care for patients who suffer with
      depression in this setting. Previously evaluated training programmes are reviewed
      and the argument is made that further development and empirical evaluation of
      depression training interventions for staff in this setting will provide services
      with evidence-based methods of training nurses and other professional care staff
      and improve the pathways to care for patients who suffer with depression.

PMID- 21862186
TI  - A systematic review of selected evidence on improving knowledge and skills
      through high-fidelity simulation.
AB  - A systematic review of the evidence published between 2000 and 2010 was
      undertaken using the following databases: CINAHL, ProQuest, MEDLINE, Science
      Direct, OVID and Chinese Academic Journal. Empirical studies determining the
      effects of high-fidelity simulation on knowledge and skills in nursing or medical
      education were considered. As a result, nine English and seventeen Chinese
      studies were retrieved. They included sixteen randomized controlled trails
      (RCTs), one nonrandomized-controlled trial, and nine quasi-experimental studies.
      The high-fidelity simulation did enhance the scores on knowledge and skill exams
      but its contribution to objective structured clinical evaluation is mixed. The
      majority of reviewed RCTs are of low methodological quality. It is necessary to
      conduct additional RCTs with larger sample sizes to determine whether performance
      can be enhanced by high-fidelity simulation.

PMID- 21862187
TI  - Nutritional status and dietary intake of acute care patients: results from the
      Nutrition Care Day Survey 2010.
AB  - BACKGROUND & AIMS: One aim of the Australasian Nutrition Care Day Survey was to
      determine the nutritional status and dietary intake of acute care hospital
      patients. METHODS: Dietitians from 56 hospitals in Australia and New Zealand
      completed a 24-h survey of nutritional status and dietary intake of adult
      hospitalised patients. Nutritional risk was evaluated using the Malnutrition
      Screening Tool. Participants 'at risk' underwent nutritional assessment using
      Subjective Global Assessment. Based on the International Classification of
      Diseases (Australian modification), participants were also deemed malnourished if
      their body mass index was <18.5 kg/m(2). Dietitians recorded participants'
      dietary intake at each main meal and snacks as 0%, 25%, 50%, 75%, or 100% of that
      offered. RESULTS: 3122 patients (mean age: 64.6 +/- 18 years) participated in the
      study. Forty-one percent of the participants were "at risk" of malnutrition.
      Overall malnutrition prevalence was 32%. Fifty-five percent of malnourished
      participants and 35% of well-nourished participants consumed <=50% of the food
      during the 24-h audit. "Not hungry" was the most common reason for not consuming
      everything offered during the audit. CONCLUSION: Malnutrition and sub-optimal
      food intake is prevalent in acute care patients across hospitals in Australia and
      New Zealand and warrants appropriate interventions.

PMID- 21862188
TI  - Movement variability during single leg jump landings in individuals with and
      without chronic ankle instability.
AB  - BACKGROUND: Repeated episodes of giving way at the ankle may be related to
      alterations in movement variability. METHODS: Eighty-eight recreational athletes
      (39 males, 49 females) were placed in 4 groups: mechanically unstable,
      functionally unstable, copers, and controls based on ankle injury history,
      episodes of giving way, and joint laxity. Lower extremity kinematics and ground
      reaction forces were measured during single leg landings from a 50% maximum
      vertical jump in the anterior, lateral, and medial directions. Ensemble curves of
      10 trials were averaged and coefficients of variation were identified for ankle,
      knee, hip, and trunk motion in 3 planes. A log(e) (ln) transformation was
      performed on the data. Mixed model analyses of variance (ANOVAs) with Tukey post
      hoc tests were utilized with Bonferroni corrections to alpha <= 0.008. FINDINGS:
      At the knee, controls were more variable than functionally unstable and copers
      for knee rotation before initial contact, and were more variable during stance
      than functionally unstable in knee rotation (P <= 0.008). Interactions during
      stance revealed controls were more variable than functionally unstable in lateral
      jumps for hip flexion, and than mechanically and functionally unstable in hip
      abduction in the anterior direction (P<=0.008). Controls were more variable than
      all other groups in hip flexion and than mechanically unstable in hip abduction
      (P <=0 .008). INTERPRETATION: Individuals with ankle instability demonstrated
      less variability at the hip and knee compared to controls during single leg jump
      landings. Inability to effectively utilize proximal joints to perform landing
      strategies may influence episodes of instability.

PMID- 21862189
TI  - Lateral wedge insoles for medial knee osteoarthritis: effects on lower limb
      frontal plane biomechanics.
AB  - BACKGROUND: Lateral wedges reduce the peak knee adduction moment and are
      advocated for knee osteoarthritis. However some patients demonstrate adverse
      biomechanical effects with treatment. Clinical management is hampered by lack of
      knowledge about their mechanism of effect. We evaluated effects of lateral wedges
      on frontal plane biomechanics, in order to elucidate mechanisms of effect.
      METHODS: Seventy three participants with knee osteoarthritis underwent gait
      analysis with and without 5 degrees  lateral wedges. Frontal plane parameters at
      the foot, knee and hip were evaluated, including peak knee adduction moment, knee
      adduction angular impulse, center of pressure displacement, ground reaction
      force, and knee-ground reaction force lever arm. FINDINGS: Lateral wedges reduced
      peak knee adduction moment and knee adduction angular impulse (-5.8% and -6.3%
      respectively, both P<0.001). Although reductions in peak moment were correlated
      with more lateral center of pressure (r=0.25, P<0.05), less varus malalignment (r
      values 0.25-0.38, P<0.05), reduced knee-ground reaction force lever arm (r=0.69,
      P<0.01), less hip adduction (r=0.24, P<0.05) and a more vertical frontal plane
      ground reaction force vector (r=0.67, P<0.001), only reduction in knee-ground
      reaction force lever arm was significantly predictive in regression analyses
      (B=0.056, adjusted R(2)=0.461, P<0.001). INTERPRETATION: Lateral wedges
      significantly reduce peak knee adduction moment and knee adduction angular
      impulse. It seems a reduced knee-ground reaction force lever arm with lateral
      wedges is the central mechanism explaining their load-reducing effects. In order
      to understand why some patients do not respond to treatment, future evaluation of
      patient characteristics that mediate wedge effects on this lever arm is required.

PMID- 21862190
TI  - Reduced European emissions of S and N--effects on air concentrations, deposition
      and soil water chemistry in Swedish forests.
AB  - Changes in sulphur and nitrogen pollution in Swedish forests have been assessed
      in relation to European emission reductions, based on measurements in the Swedish
      Throughfall Monitoring Network. Measurements were analysed over 20 years with a
      focus on the 12-year period 1996 to 2008. Air concentrations of SO(2) and NO(2),
      have decreased. The SO(4)-deposition has decreased in parallel with the European
      emission reductions. Soil water SO(4)-concentrations have decreased at most sites
      but the pH, ANC and inorganic Al-concentrations indicated acidification recovery
      only at some of the sites. No changes in the bulk deposition of inorganic
      nitrogen could be demonstrated. Elevated NO(3)-concentrations in the soil water
      occurred at irregular occasions at some southern sites. Despite considerable air
      pollution emission reductions in Europe, acidification recovery in Swedish
      forests soils is slow. Nitrogen deposition to Swedish forests continues at
      elevated levels that may lead to leaching of nitrate to surface waters.

PMID- 21862191
TI  - Long term remediation of highly polluted acid mine drainage: a sustainable
      approach to restore the environmental quality of the Odiel river basin.
AB  - During 20 months of proper operation the full scale passive treatment in Mina
      Esperanza (SW Spain) produced around 100 mg/L of ferric iron in the aeration
      cascades, removing an average net acidity up to 1500 mg/L as CaCO(3) and not
      having any significant clogging problem. Complete Al, As, Cd, Cr, Cu, Ti and V
      removal from the water was accomplished through almost the entire operation time
      while Fe removal ranged between 170 and 620 mg/L. The system operated at a mean
      inflow rate of 43 m(3)/day achieving an acid load reduction of 597 g.(m(2) day)(
      1), more than 10 times higher than the generally accepted 40 g.(m(2) day)(-1)
      value commonly used as a passive treatment system designing criteria. The high
      performance achieved by the passive treatment system at Mina Esperanza
      demonstrates that this innovative treatment design is a simple, efficient and
      long lasting remediation option to treat highly polluted acid mine drainage.

PMID- 21862192
TI  - Vertical fluxes of aromatic and aliphatic hydrocarbons in the Northwestern
      Mediterranean Sea.
AB  - Aliphatic and aromatic hydrocarbon fluxes were measured in time series sediment
      trap samples at 200 m and at 1000 m depths in the open Northwestern Mediterranean
      Sea, from December 2000 to July 2002. Averaged fluxes of n-alkanes, UCM and T
      PAH(35) were 2.96 +/- 2.60 MUg m(-2) d(-1), 64 +/- 60 MUg m(-2) d(-1) and 0.68 +/
      0.59 MUg m(-2) d(-1), respectively. Molecular compositions of both hydrocarbon
      classes showed a contamination in petrogenic hydrocarbons well above the
      background levels of such an open site, whereas pyrolytic hydrocarbons stand in
      the range of other open Mediterranean locations. Fluxes displayed ample
      interannual and seasonal variabilities, mainly related to mass flux variation
      while concentration evolutions trigger secondary changes in pollutant fluxes.
      High lithogenic flux events exported particles with a larger pollutant load than
      biogenic particles formed during the spring bloom and during the summer. Sinking
      hydrocarbons were efficiently transported from 200 m to 1000 m.

PMID- 21862194
TI  - Difficulties leaving home: a cross-sectional study of delays in seeking emergency
      obstetric care in Herat, Afghanistan.
AB  - This study used an analytical cross-sectional design to identify risk factors
      associated with delays in care-seeking among women admitted in life-threatening
      conditions to a maternity hospital in Herat, Afghanistan, from February 2007 to
      January 2008. Disease-specific criteria of 'near-miss' were used to identify
      women in life-threatening conditions. Among 472 eligible women and their
      husbands, 411 paired interviews were conducted, and information on socio
      demographic factors; the woman's status and social resources; the husband's
      social networks; health care accessibility and utilisation; care-seeking costs;
      and community characteristics were obtained. Decision and departure delays were
      assessed quantitatively from reported timings of symptom recognition, care
      seeking decision, and departure for health facilities. Censored normal regression
      analyses suggest that although determinants of decision delay were influenced by
      the nature and symptoms of complications, uptake of antenatal care (ANC) and the
      birth plan reduced decision delay at the time of the obstetric emergency. Access
      to care and social networks reduced departure delay. Programmatic efforts may be
      directed towards exploiting the roles of ANC and social resources in facilitating
      access to emergency obstetric care.

PMID- 21862193
TI  - When a patient refuses life-saving care: issues raised when treating a Jehovah's
      Witness.
AB  - Patients who are Jehovah's Witnesses frequently cross the path of nephrologists
      when they are acutely ill in the intensive care unit and stable in the long-term
      setting. It is important that we as a group have a rudimentary understanding of
      their philosophy about blood transfusion so that we can be proactive in their
      management. We use a case as a launching point to discuss the origins of the
      faith and the decision to refuse blood, as well as potential therapeutic
      strategies that can be used to improve the care of these patients. Improvement in
      our understanding as physicians will facilitate a more productive conversation
      with our patients about a complex and emotional issue.

PMID- 21862195
TI  - Sexing the baby: Part 2--Applying dynamic systems theory to the emergences of sex
      related differences in infants and toddlers.
AB  - During the first three years of life, children acquire knowledge about their own
      gender and the gendered nature of their environment. At the same time, sex
      related behavioral differences emerge. How are we to understand the processes by
      which bodily differentiation, behavioral differentiation and gendered knowledge
      intertwine to produce male and female, masculine and feminine? In this article,
      we describe four central developmental systems concepts applied by psychologists
      to the study of early human development and develop them in enough depth to show
      how they play out, and what sort of knowledge-gathering strategies they require.
      The general theoretical approach to understanding the emergence of
      bodily/behavioral difference has broad applicability for the health sciences and
      for the study of gender disparities. Using dynamic systems theory will deepen and
      extend the reach of theories of embodiment current in the health sciences
      literature.

PMID- 21862196
TI  - Allergy to hazelnut in adults: a two-step study.
AB  - BACKGROUND: Although hazelnut consumption is very high in Turkey, the prevalence
      of hazelnut allergy is still unknown. This study's objective was to investigate
      the prevalence of hazelnut sensitisation and to verify its clinical importance
      using double-blind, placebo-controlled challenge (DBPCFC) in an adult population.
      METHODS: Prick-to-prick skin tests were performed with fresh hazelnut in 904
      patients admitted to the allergy department. Among the 904 subjects, 20 patients
      with a history of allergic reactions to hazelnut and/or positive skin tests were
      recalled for further evaluation. Specific IgE was measured in these subjects.
      Eleven (11/20) patients accepted to undergo DBPCFC with hazelnut. RESULTS: Among
      the 904 individuals, the history of reactions to hazelnut was positive in 16
      subjects (1.8%); prick-to-prick skin tests were positive in 13 (1.4%); prick
      tests with the commercial product were positive in nine (0.9%); and history plus
      skin tests were positive in 16 (1.8%). Specific IgE to hazelnut was positive in
      only three patients. DBPCFC was conducted in 11 subjects with a positivity rate
      of 63.6% (7/11). We observed six mild and one moderate systemic reactions during
      the DBPCFC. Among seven subjects with a positive DBPCFC, six (85.7%) had a
      history of hazelnut allergy, and five (71.4%) had both history and skin test
      positivity. CONCLUSION: Skin test sensitisation to hazelnut was found to be 1.76%
      (16/904) which is similar to the sensitisation rate in previous reports. However,
      DBPCFC was positive in 63% of cases with a history of hazelnut allergy and/or
      positive skin tests in this study. These results indicate that the presence of
      history with a positive skin test can be suggestive of hazelnut allergy; however
      an oral food challenge is needed to confirm the diagnosis.

PMID- 21862197
TI  - Assessing caries, dental plaque and salivary flow in asthmatic adolescents using
      inhaled corticosteroids.
AB  - BACKGROUND: A number of studies have reported that inhaled corticosteroids may
      cause a greater incidence of caries, reduced salivary flow, changes in saliva
      composition and an increased frequency of dental plaque, probably through
      alterations in the oral microbiota. The objective was to compare the frequency of
      caries, dental plaque and non-stimulated salivary flow rate among asthmatic
      adolescents using inhaled corticosteroids and non-asthmatic adolescents, as well
      as the salivary biochemical parameters (pH and leucocytes) in both groups.
      METHODS: This research has a descriptive cross-sectional design to compare dental
      health of 40 asthmatics on inhaled corticosteroids and 40 non-asthmatic
      adolescents (median age 13 years). RESULTS: The findings were a higher number of
      tooth surfaces affected by dental caries (median 4 versus 1.5), and more dental
      plaques (median 70.5 versus 60.7) among asthmatic adolescents. They also had a
      significantly higher frequency of salivary leucocytes. The non-stimulated
      salivary flow was similar in both groups. CONCLUSIONS: The results suggest an
      association between the use of inhaled corticosteroids and an increased risk of
      dental caries and bacterial plaque, which calls for special attention of these
      patients by doctors and dental health professionals.

PMID- 21862198
TI  - Anti-inflammatory effects of curcumin in a murine model of chronic asthma.
AB  - BACKGROUND: Curcumin, a dietary pigment responsible for the yellow colour of
      curry, has been used for the treatment of inflammatory diseases and exhibits a
      variety of pharmacological effects. METHODS: Forty-two BALB/c mice were divided
      into six groups: I, II, III, IV, V, and control group. All groups except the
      controls were sensitised and challenged with ovalbumin. Group I received
      nebulised saline in challenge period. Mice in groups II, III, IV, and V were
      administered curcumin at a dose of 10 mg/kg, curcumin 20 mg/kg, dexamethasone 1
      mg/kg, and dimethyl sulfoxide 1 mg/kg, respectively, intraperitoneally once a day
      for the final 5 days of the challenge period. Animals were sacrificed 24 h after
      the last drug administration and the airway samples were evaluated histologically
      by light microscopy. RESULTS: All histological parameters in Group III improved
      similar to Group IV when compared to Group I. In Group II, only thickness of
      epithelium was significantly lower compared with regard to Group I. All variables
      except epithelium thicknesses were found to be significantly better in Group III
      compared to Group II. CONCLUSIONS: In our study, we demonstrated that curcumin
      administration alleviates the pathological changes of chronic asthma. Curcumin
      might be a promising therapy for asthma in the future.

PMID- 21862199
TI  - Urogenital pathogen inhibition and compatibility between vaginal Lactobacillus
      strains to be considered as probiotic candidates.
AB  - OBJECTIVES: To evaluate the production of inhibitory substances against several
      urogenital pathogens and to determine the compatibility between selected vaginal
      lactobacilli to be considered as probiotic candidates. STUDY DESIGN: The
      inhibitory activity of 38 vaginal Lactobacillus strains against urogenital
      pathogens was assessed using the agar plate diffusion. METHOD: The production of
      hydrogen peroxide was determined by the semi-qualitative tetramethyl-benzidine
      peroxidase assay and that of lactic acid by high performance liquid
      chromatography. Pre-selected lactobacilli were genetically identified by
      ribosomal 16S-DNA sequencing and used to determine the compatibility of strains.
      Correlation values between some inhibitory properties were calculated. RESULTS:
      45% of the lactobacilli assayed inhibited the growth of various urogenital
      pathogens, except Candida albicans, mainly by the effect of organic acids. Even
      though 71% of the Lactobacillus strains produced hydrogen peroxide in the semi
      qualitative test, the antimicrobial effect of the oxidative metabolite on
      pathogens was not detected under the experimental conditions assayed. On the
      other hand, the inhibition spectrum of salivaricin CRL 1328 was widened with
      respect to the one previously reported by our research team. With respect to the
      degree of interaction between the pre-selected lactobacilli, most of them showed
      inhibition of at least one strain, mainly due to the effects of both organic
      acids and hydrogen peroxide. CONCLUSION: Several lactobacilli that showed
      inhibitory activity against urogenital pathogens or produced hydrogen peroxide
      are compatible between them. Therefore, different potential combinations of
      strains are proposed for their inclusion in the design of probiotic products to
      be vaginally administered for the prevention of urogenital infections in women.

PMID- 21862200
TI  - Learning curve of volume measurements by three-dimensional ultrasound with a
      rotational multi-planar technique (VOCAL), an in vitro study.

PMID- 21862202
TI  - Studies on solvent extraction of iron(III) as a step for conversion of a waste
      effluent to a value added product.
AB  - Solvent extraction of iron(III) from actual sulphate waste pickle liquor was
      investigated using trialkylphosphine oxide diluted with kerosene. The waste
      pickle liquor was procured from a local company which deals with the
      manufacturing of pipes and tubes made of iron and steel. Various parameters were
      studied to optimise a suitable condition for the maximum extraction of iron. The
      composition of the aqueous feed used in the experiment was 60.88 g/L Fe(III), 53
      g/L acid with traces of Cu, Ni and Co. An ambient extraction at 30  degrees C
      yielded acceptable kinetics and loading efficiency for 40% trialkylphosphine
      oxide with a saturated loading capacity of 51.85 g/L in four contacts at O/A
      ratio of 1/1 in a multiple contact mode. Iron from the loaded organic was
      stripped using various strippants such as distilled water, H(2)SO(4) and oxalic
      acid. Since only 32% of loaded Fe could be stripped with 2 M H(2)SO(4) in five
      contacts, further stripping was done with 5% oxalic acid which showed a very
      promising result. It was found that almost 100% of Fe(III) could be stripped out
      with 5% oxalic acid at O/A of 1/1 in five contacts.

PMID- 21862203
TI  - Assessing options for the development of surface water flood warning in England
      and Wales.
AB  - This paper explores the technical options for warning of surface water flooding
      in England and Wales and presents the results of an Environment Agency funded
      project. Following the extensive surface water flooding experienced in summer
      2007 a rainfall threshold-based Extreme Rainfall Alert (ERA) was piloted by the
      Met Office and Environment Agency providing initial steps towards the
      establishment of a warning for some types of surface water flooding. The findings
      of this paper are based primarily on feedback on technical options from a range
      of professionals involved in flood forecasting and warning and flood risk
      management, about the current alerts and about the potential options for
      developing a more targeted surface water flood warning service. Providing surface
      water flooding warnings presents a set of technical, forecasting and warning
      challenges related to the rapid onset of flooding, the localised nature of the
      flooding, and the linking of rainfall and flood forecasts to flood likelihood and
      impact on the ground. Some examples of rainfall alerting and surface water flood
      warning services from other countries are evaluated, as well as a small number of
      recently implemented local services in England and Wales. Various potential
      options for implementation of a service are then explored and assessed. The paper
      concludes that development of a surface water flood warning service for England
      and Wales is feasible and is likely to be useful to emergency responders and
      operational agencies, although developing such a service for the pluvial
      components of this type of flooding is likely to be feasible sooner than for
      other components of surface water flooding such as that caused by sewers. A
      targeted surface water flood warning service could be developed for professional
      emergency responders in the first instance rather than for the public for whom
      such a service without further operational testing and piloting would be
      premature.

PMID- 21862201
TI  - Cholesterol and benign prostate disease.
AB  - The origins of benign prostatic diseases, such as benign prostatic hyperplasia
      (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly
      understood. Patients suffering from benign prostatic symptoms report a
      substantially reduced quality of life, and the relationship between benign
      prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH
      and CP/CPPS are limited, however an apparent association between BPH symptoms and
      cardiovascular disease (CVD) has been consistently reported. The prostate
      synthesizes and stores large amounts of cholesterol and prostate tissues may be
      particularly sensitive to perturbations in cholesterol metabolism.
      Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH.
      Animal model and clinical trial findings suggest that agents that inhibit
      cholesterol absorption from the intestine, such as the class of compounds known
      as polyene macrolides, can reduce prostate gland size and improve lower urinary
      tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering
      drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell
      growth and survival pathways depend in part on cholesterol-sensitive biochemical
      mechanisms. Here we review the evidence that cholesterol metabolism plays a role
      in the incidence of benign prostate disease and we highlight possible therapeutic
      approaches based on this concept.

PMID- 21862204
TI  - What are the limitations of endoscopic management of urothelial carcinoma of the
      upper urinary tract?

PMID- 21862205
TI  - Baseline prostate-specific antigen testing at a young age.
AB  - CONTEXT: Prostate cancer screening is highly controversial, including the age to
      begin prostate-specific antigen (PSA) testing. Several studies have evaluated the
      usefulness of baseline PSA measurements at a young age. OBJECTIVE: Review the
      literature on baseline PSA testing at a young age (<=60 yr) for the prediction of
      prostate cancer risk and prognosis. EVIDENCE ACQUISITION: PubMed was searched for
      English-language publications on baseline PSA and prostate cancer for the period
      ending April 2011. EVIDENCE SYNTHESIS: In most published series, median PSA
      levels in the general male population range from approximately 0.4 to 0.7 ng/ml
      in men in their 40s and from approximately 0.7 to 1.0 ng/ml in men in their 50s.
      Evidence from both nonscreening and screening populations has demonstrated the
      predictive value of a single baseline PSA measurement for prostate cancer risk
      assessment. Specifically, men with baseline PSA levels above the age-group
      specific median have a greater risk of prostate cancer diagnosis during the next
      20-25 yr. Additional studies confirmed that higher baseline PSA levels at a young
      age are also associated with a greater risk of aggressive disease, metastasis,
      and disease-specific mortality many years later. CONCLUSIONS: Baseline PSA
      measurements at a young age are significant predictors of later prostate cancer
      diagnosis and disease-specific outcomes. Thus baseline PSA testing may be used
      for risk stratification and to guide screening protocols.

PMID- 21862206
TI  - Salvage lymph node dissection in recurrent prostate cancer patients.

PMID- 21862207
TI  - Comparison of coil types in aneurysm recurrence.
AB  - OBJECTIVE: Coiling of saccular aneurysms may result in recurrence requiring
      retreatment. Aneurysm recanalization may depend on coil type. Coil variations
      include bare platinum, polymer coated (Matrix), and hydrophylic gel coated
      (HydroCoil) coils. The effect of coil type on aneurysm recurrence was evaluated.
      METHODS: Retrospective analysis of prospectively collected database of 100
      consecutive, 4-15mm, coiled, ruptured aneurysms. There were 3 groups based on
      coil type: (1) bare platinum, (2) HydroCoil, and (3) Matrix. Data collected
      included age, gender, aneurysm location, follow-up, retreatments and angiographic
      occlusion and recanalization. RESULTS: There were 42.4% (n=14) anterior and 57.5%
      (n=19) posterior circulation aneurysms in the bare platinum, 61.5% (n=16) and
      38.45% (n=10) in HydroCoil, and 43.9% (n=18) and 56.1% (n=23) in the Matrix
      groups. Retreatment was required in 4 (12.1%) bare platinum, 9 (21.9%) Matrix,
      and 3 (11.5%) HydroCoil groups. On follow-up angiography HydroCoil group had the
      most number of completely occluded and least number of residual aneurysms
      (P=0.01), HydroCoils showed the least (n=4), bare platinum an intermediate (n=7),
      and matrix group the greatest tendency (n=15) to recanalize. CONCLUSIONS: Matrix
      coils were most likely to need retreatment. Retreatment rates were comparable for
      bare platinum and HydroCoils. Follow-up angiography demonstrated statistically
      significant attenuation of residual aneurysms for HydroCoils. Matrix group had
      the greatest and HydroCoils the least tendency to recanalize. Factors other than
      coil surface-coating may attenuate aneurysm recurrence.

PMID- 21862208
TI  - How obliteration of petrosal air cells by vestibular schwannoma influences the
      risk of postoperative CSF fistula.
AB  - INTRODUCTION: For postoperative CSF-fistula prevention a better understanding of
      its origins and risk factors is necessary. To identify the role of the tumor
      growth for the risk to develop CSF-fistula we performed a retrospective analysis.
      METHODS: 519 patients between the years 2000 and 2007 had a retrosigmoidal
      surgical removal of vestibular schwannoma in a standardized procedure. 22 CSF
      fistula-patients were chosen for evaluation. 78 patients were randomly selected
      as control group in four equally sized cohorts: male/female with small/large
      tumors. Preoperative CT-scans were analyzed regarding IAC-length, diameter of the
      IAC porus (IAP), tumor size and pneumatization of the posterior wall (PW) of the
      IAC. RESULTS: The mean length of the IAC was 1.2 cm, SD 0.17. There was a
      significant difference between the diameter of the IAP in cases of small tumors
      and those of large tumors. Patients with small tumors also showed a larger
      fraction with visible pneumatization of the PW (34.88%) in the CT-scan than
      patients with large tumors (24.07%). There is a positive correlation between
      tumor grade and diameter of the IAP. At the same time there is an inverse
      correlation between tumor grade and pneumatization of the PW. CONCLUSIONS:
      Widening of the IAC by tumor growth may leads to obliteration of air cells in the
      PW and therefore can be protective concerning CSF-fistula. At the same time
      patients with small tumors and a visible pneumatization in the PW must be
      expected to have a higher risk of CSF-fistula.

PMID- 21862209
TI  - Phenylketonuria is still a major cause of mental retardation in Tunisia despite
      the possibility of treatment.
AB  - BACKGROUND AND OBJECTIVE: Accumulation of phenylalanine following a deficiency of
      phenylalanine hydroxylase activity generates a brain damage with mental
      retardation: phenylketonuria (PKU). In the developing countries, where PKU
      systematic neonatal screening program is not established yet, the management of
      PKU handicap is not properly carried out. The aim of this study was to estimate
      the frequency of the PKU diagnosed following clinical features anomalies, to
      provide information about the untreated PKU patients profile in Tunisia not
      covered by neonatal screening. Also it is stressed that treated patients have a
      normal development. PATIENTS AND METHODS: This is a retrospective study of 156
      cases of PKU detected in Tunisia over 20 years following symptoms suggestive of
      inherited metabolic disease. Phenylalaninemia level was performed by fluorometric
      method. Among them 9 patients were treated. RESULTS: The PKU estimated frequency
      was 1/7631. The diagnosis mean age was 4 years. The phenylalaninemia mean was
      1680 MUmol/L; the classical PKU form accounted for 85.3% of cases and the
      dominant clinical symptoms were: mental retardation (88.2%), motor delays
      (87.7%), speech difficulties (83.2%) and pigmentation anomalies (61.7%). The
      treated patients responded to treatment and showed a normal development.
      CONCLUSION: The establishment of neonatal screening should be a priority to avoid
      cases of mentally retardation.

PMID- 21862210
TI  - Prevalence and incidence of dementia among 75-80-year-old community-dwelling
      elderly in different districts of Antwerp, Belgium: the Antwerp Cognition (ANCOG)
      Study.
AB  - OBJECTIVE: To analyse the prevalence and incidence of dementia in a population of
      community-dwelling elderly (aged 75-80), living in socio-economically differing
      districts of Antwerp (Belgium), taking into account possible gender and
      educational differences. METHODS: A longitudinal cohort study (N=825) with a 3
      year follow-up period (N=363). The Mini Mental State Examination (MMSE) was used
      as a primary screen of cognitive functioning. Scoring 21 or below led to a second
      phase examination by a neurologist, including the CAMDEX-R-N and a neurological
      examination, to provide a tentative aetiological diagnosis of dementia. These
      procedures were conducted annually during a 3-year follow-up period. RESULTS: In
      accordance with international literature, the overall prevalence rate of dementia
      was 8.7%. The cumulative incidence rate (IR) of dementia was 36.60 per 1000Py
      with annual IRs ranging from 34.39 over 35.16 to 49.04 per 1000Py. Dementia of
      the Alzheimer type (DAT) was the most occurring prevalent and incident cause.
      Women appeared to be at higher risk and the occurrence of cognitive deterioration
      was more prominent in districts with lower socio-economic status, possibly
      related to a lower education level. CONCLUSION: We demonstrate dementia is a
      considerable health problem in an urban Belgian population of community-dwelling
      elderly aged between 75 and 80 years old. In order to prepare health care and
      social security systems for the future management of dementia, proper
      epidemiological insight into the current and future magnitude of the burden of
      dementia, taking into account socio-economic differences, to which this study
      contributes, are required.

PMID- 21862212
TI  - Targeting the ceramide system in cancer.
AB  - Sphingolipids, in particular ceramide, have been described as important
      components of cellular signalling pathways. Ceramide can be produced via multiple
      mechanisms including through the hydrolysis of sphingomyelin by acid and neutral
      sphingomyelinase or by a de novo synthesis pathway. Recent studies have
      identified sphingomyelinases and ceramide synthases as important targets for
      gamma-irradiation and chemotherapeutic drugs. Likewise, common cancer treatment
      modalities, such as gamma-irradiation and many chemotherapeutic agents, induce
      cell death via the generation of ceramide. This suggests that the manipulation of
      ceramide production and metabolism could offer promising means for the
      enhancement of anti-tumor therapies. The focus of this mini-review will be to
      discuss contemporary evidence suggesting that ceramide forming pathways and
      ceramide itself are important targets for the treatment of tumors and the
      development of novel tumor treatment strategies.

PMID- 21862211
TI  - Histone deacetylase inhibitor valproic acid suppresses the growth and increases
      the androgen responsiveness of prostate cancer cells.
AB  - We identified the molecular target by histone deacetylase (HDAC) inhibitors for
      exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors
      treatment, LNCaP cell growth was suppressed, correlating with increased cellular
      prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine
      phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4
      acetylation and methylation increased and cyclin proteins decreased. In PAcP
      shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression
      was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C
      81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth
      suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase
      androgen responsiveness.

PMID- 21862213
TI  - The oxidative corrosion of carbide inclusions at the surface of uranium metal
      during exposure to water vapour.
AB  - The reaction between uranium and water vapour has been well investigated, however
      discrepancies exist between the described kinetic laws, pressure dependence of
      the reaction rate constant and activation energies. Here this problem is looked
      at by examining the influence of impurities in the form of carbide inclusions on
      the reaction. Samples of uranium containing 600 ppm carbon were analysed during
      and after exposure to water vapour at 19 mbar pressure, in an environmental
      scanning electron microscope (ESEM) system. After water exposure, samples were
      analysed using secondary ion mass spectrometry (SIMS), focused ion beam (FIB)
      imaging and sectioning and transmission electron microscopy (TEM) with X-ray
      diffraction (micro-XRD). The results of the current study indicate that carbide
      particles on the surface of uranium readily react with water vapour to form
      voluminous UO(3) . xH(2)O growths at rates significantly faster than that of the
      metal. The observation may also have implications for previous experimental
      studies of uranium-water interactions, where the presence of differing levels of
      undetected carbide may partly account for the discrepancies observed between
      datasets.

PMID- 21862214
TI  - Study of thermodynamics and dynamics of removing Cu(II) by biosorption membrane
      of Penicillium biomass.
AB  - Based on the integration of biosorption and membrane-separation, a novel
      biosorption membrane with good mechanical property was prepared by immobilizing
      Penicillium biomass with cross-linked chitosan on fabric. The ability of the low
      cost biosorption membrane to remove Cu(II) ions from a solution was studied
      through batch and continuous experiments. Langmuir adsorption isotherm models
      were found to accurately fit the batch experimental data (R(2) > 0.99) indicating
      that sorption was of monolayer-mode. The uptake of Cu(II) could reach 38 mg/g at
      its initial concentration of 200 mg/L in the solution. Continuous biosorption was
      investigated in a column and the effects of the height, flow rate and initial
      concentration of Cu(II) were studied. The Bed Depth Service Time model (BDST) was
      applied to simulate column adsorption data. The breakthrough time at different
      flow rates and initial concentrations was accurately predicted by the model
      (error < 8%). The uptake of Cu(II) could reach 38.3 mg/g at height 30 cm, flow
      rate 5 mL/min, initial concentration of Cu(II) 200 mg/L. The biosorption membrane
      was regenerated by washing with 0.05 mol/L solution of HCl, and breakthrough
      curves remained fairly unchanged after 10 cycles of adsorption-desorption.

PMID- 21862215
TI  - Surface activated carbon nanospheres for fast adsorption of silver ions from
      aqueous solutions.
AB  - We report the synthesis and activation of colloidal carbon nanospheres (CNS) for
      adsorption of Ag(I) ions from aqueous solutions. CNS (400-500 nm in diameter) was
      synthesized via simple hydrothermal treatment of glucose solution. The surface of
      nonporous CNS after being activated by NaOH was enriched with -OH and -COO(-)
      functional groups. Despite the low surface area (<15m(2)/g), the activated CNS
      exhibited a high adsorption capacity of 152 mg silver/g. Under batch conditions,
      all Ag(I) ions can be completely adsorbed in less than 6 min with the initial
      Ag(I) concentrations lower than 2 ppm. This can be attributed to the minimum mass
      transfer resistance as Ag(I) ions were all deposited and reduced as Ag(0)
      nanoparticles on the external surface of CNS. The kinetic data can be well fitted
      to the pseudo-second-order kinetics model. The adsorbed silver can be easily
      recovered by dilute acid solutions and the CNS can be reactivated by the same
      treatment with NaOH solution. The excellent adsorption performance and
      reusability have also been demonstrated in a continuous mode. The NaOH activated
      CNS reported here could represent a new type of low-cost and efficient adsorbent
      nanomaterials for removal of trace Ag(I) ions for drinking water production.

PMID- 21862216
TI  - Synthesis of magnetic wheat straw for arsenic adsorption.
AB  - Magnetic wheat straw (MWS) with different Fe(3)O(4) content was synthesized by
      using in-situ co-precipitation method. It was characterized by powder X-ray
      diffraction (XRD) and vibrating sample magnetometer (VSM). This material can be
      used for arsenic adsorption from water, and can be easily separated by applied
      magnetic field. The introduction of wheat straw template highly enhanced the
      arsenic adsorption of Fe(3)O(4). Among three adsorption isotherm models examined,
      the data fitted Langmuir model better. Fe(3)O(4) content and initial pH value
      influenced its adsorption behavior. Higher Fe(3)O(4) content corresponded to a
      higher adsorption capacity. In the pH range of 3-11, As(V) adsorption was
      decreased with increasing of pH; As(III) adsorption had the highest capacity at
      pH 7-9. Moreover, by using 0.1 mol L(-1) NaOH aqueous solution, it could be
      regenerated. This work provided an efficient way for making use of agricultural
      waste.

PMID- 21862218
TI  - Degradation of methyl orange by Zn0 assisted with silica gel.
AB  - The degradation of methyl orange (MO) by Zn(0) assisted with silica gel was
      investigated under different conditions. The results show that the degradation of
      MO by Zn(0) alone was slow and incomplete due to the rapid corrosion of Zn(0)
      particles on surface. However, the degradation of MO can be markedly enhanced
      when Zn(0) and silica gel coexist, even under neutral and alkaline conditions. MO
      removal was improved with a pH decrease, an increase of the initial amount of
      silica gel and Zn(0), and specific surface area of silica gel. The degradation of
      MO by Zn(0) assisted with silica gel can be described by a pseudo-first-order
      kinetic. And the surface of Zn(0) before and after the reaction was characterized
      by the microscopic analysis of morphology, revealing the potential mechanism
      responsible for the enhanced reactivity of silica gel.

PMID- 21862217
TI  - Uptake kinetics of different arsenic species in lowland and upland rice colonized
      with Glomus intraradices.
AB  - The effect of Glomus intraradices on four As species (arsenate; arsenite;
      dimethylarsinic acid, DMA; and monomethylarsonic acid, MMA) uptake by lowland
      rice and upland rice were investigated based on two experiments: (1) high (0-0.05
      mM) and low (0-2.5mM) - affinity uptake kinetics of four As species in the short
      term, and (2) As speciation in rice treated with 1mM arsenate, arsenite, DMA or
      MMA solutions. The results showed that mycorrhizal roots of two rice cultivars
      reduced the arsenate uptake significantly (P<0.001) in low-affinity uptake
      system, and decreased the uptake of arsenite and MMA noticeably (P<0.05) in high
      or low-affinity uptake systems. The four As species influx have significant
      differences (P<0.05) between two rice varieties in low-affinity uptake systems.
      In the arsenate treatment, the ratio of arsenate/arsenite reduced in shoots while
      increased in roots because of G. intraradices presence.

PMID- 21862219
TI  - Auditory symptom provocation in dental phobia: a near-infrared spectroscopy
      study.
AB  - The act of drilling a tooth belongs to the most feared situations of patients
      suffering from dental phobia. We presented 25 female patients and 24 nonphobic
      women with the sound of a dental drill, pleasant and neutral sounds. Brain
      activation was recorded via near infrared spectroscopy in fronto-parietal and
      premotor areas. The groups differed in supplementary motor area (SMA)
      recruitment. Relative to controls, the phobics displayed increased oxy hemoglobin
      while presented with the phobia-relevant sound, but showed comparable activation
      in the other conditions. As the SMA is engaged in the preparation of motor
      actions, the increased response in patients might mirror the priming of flight
      behavior during exposure. We found no indication of an emotional modulation of
      parietal and dorsomedial prefrontal cortex activation.

PMID- 21862220
TI  - Evaluation of the fear-avoidance model with health care workers experiencing
      acute/subacute pain.
AB  - Studies in the literature do not show clear evidence supporting the relationship
      between pain and depressive symptoms in individuals experiencing acute/subacute
      pain compared to those experiencing chronic pain. However, more information is
      needed about which variables act as mediators in the pain-depression relationship
      in people having acute/subacute pain, before pain becomes chronic. Our objectives
      were to test the suitability of the fear-avoidance model in a sample of 110
      health care workers experiencing acute/subacute pain using path analyses, to
      improve the model as needed, and to examine a model involving both pain
      catastrophizing and pain self-efficacy with work status as a final outcome.
      Overall, the results indicated that adjustments to the fear-avoidance model were
      required for people experiencing acute/subacute pain, in which fear-avoidance
      beliefs and depressive symptoms were concurrent rather than sequential. The
      catastrophizing concept was most closely associated with depressive symptoms,
      while pain self-efficacy was directly associated with fear-avoidance beliefs and
      indirectly to work outcomes. Assessing and modifying pain self-efficacy in
      acute/subacute pain patients is important for interventions aiming to decrease
      fear-avoidance and improve work outcomes.

PMID- 21862221
TI  - The transcription factor Smad-interacting protein 1 controls pain sensitivity via
      modulation of DRG neuron excitability.
AB  - The perception of pain is initiated by the transduction of noxious stimuli
      through specialized ion channels and receptors expressed by primary nociceptive
      neurons. The molecular mechanisms that orchestrate the expression and function of
      ion channels relevant for pain processing are poorly understood. We demonstrate
      here a central role of the transcription factor Smad-interacting protein 1
      (Sip1/Zfhx1b/Zeb2), a 2-handed zinc finger DNA-binding protein with essential
      functions in neural crest and forebrain development, in controlling nociceptive
      neuron excitability and pain sensitivity. Mutant mice lacking 1 Zfhx1b allele
      displayed decreased thermal pain responses, whereas mechanical pain was
      unaffected. In parallel, repetitive firing of capsaicin/heat-sensitive
      nociceptive DRG neurons was markedly impaired. Analysis of the voltage-gated
      currents underlying repetitive firing revealed a significant increase in
      persistent sodium currents and a reduction in delayed rectifier potassium
      currents. Modeling experiments in conjunction with experimental results suggest
      that these changes cause a depolarization-induced block of action potential
      propagation past the DRG axon T-junction. These data suggest that Sip1 controls
      the transduction properties of heat-sensitive primary sensory neurons and thus
      thermal pain sensitivity in a novel manner via coordinated changes in DRG-neuron
      voltage-gated ion channels.

PMID- 21862222
TI  - The socioeconomic burden of parasitic zoonoses: global trends.
AB  - Diseases resulting from zoonotic transmission of parasites are common. Humans
      become infected through food, water, soil and close contact with animals. Most
      parasitic zoonoses are neglected diseases despite causing a considerable global
      burden of ill health in humans and having a substantial financial burden on
      livestock industries. This review aims to bring together the current data
      available on global burden estimates of parasitic zoonoses and indicate any
      changes in the trends of these diseases. There is a clear need of such
      information as interventions to control zoonoses are often in their animal hosts.
      The costs of such interventions together with animal health issues will drive the
      cost effectiveness of intervention strategies. What is apparent is that
      collectively, parasitic zoonoses probably have a similar human disease burden to
      any one of the big three human infectious diseases: malaria, tuberculosis or HIV
      in addition to animal health burden. Although the global burden for most
      parasitic zoonoses is not yet known, the major contributors to the global burden
      of parasitic zoonoses are toxoplasmosis, food borne trematode infections,
      cysticercosis, echinococcosis, leishmaniosis and zoonotic schistosomosis. In
      addition, diarrhoea resulting from zoonotic protozoa may have a significant
      impact.

PMID- 21862223
TI  - Intranasal oxytocin enhances emotion recognition from dynamic facial expressions
      and leaves eye-gaze unaffected.
AB  - Previous studies have shown that oxytocin improves the encoding and recognition
      of facial expressions, which has been proposed to be mediated by an increased
      exploration of the eye region during face processing. In the present study, we
      used eye tracking to assess visual attention to the eye region while participants
      performed a dynamic facial emotion recognition task. In a double-blind, placebo
      controlled between-subjects design participants received 24 IU intranasal
      oxytocin (n = 23) or a placebo (n = 24). Although oxytocin administration had no
      effect on participants' visual scanning of emotional faces, it generally enhanced
      recognition performance, as the oxytocin group recognized emotional expressions
      at lower intensity levels. These findings suggest that oxytocin-induced
      improvement of facial emotion recognition is independent of modulations in overt
      visual attention.

PMID- 21862224
TI  - Periodic maternal separation decreases hippocampal neurogenesis without affecting
      basal corticosterone during the stress hyporesponsive period, but alters HPA axis
      and coping behavior in adulthood.
AB  - Although not directly evaluated, the early rise of glucocorticoid (GC) levels, as
      occur after exposure to adverse early life experience, are assumed to affect
      hippocampal ontogeny by altering the hippocampus negative feedback on adult HPA
      axis. To test whether hippocampal ontogeny is affected by early exposure to
      stress we estimated the survival of recently formed hippocampal granule cells in
      rat pups subjected to periodic maternal separation (180 min/day; MS180) from
      postnatal days (PND) 1 to 14. Accordingly, MS180 pups injected with
      bromodeoxyuridine (BrdU, 50 mg/kg, ip) at PND 5 showed decreased density of
      doublecortin (DCX) positive BrdU-labeled cells at PND 15. MS180 and AFR pups
      showed similar corticosterone (CORT) basal levels between PND 3 and 12, whereas
      adult MS180 rats presented with higher CORT levels than AFR adults. Nonetheless,
      both AFR and MS180 pups and adults showed similar transient increments of CORT
      levels in response to stress. In addition, MS180 had no effect on the adult
      anxiety-like behavior evaluated in the elevated plus maze, but evoked a passive
      coping strategy in the forced swimming test. The data show that the decrease in
      hippocampal neurogenesis is an early onset phenomenon, and suggests that adverse
      experiences alter hippocampal ontogeny without chronic elevation of GC levels.

PMID- 21862225
TI  - Challenges of measuring diurnal cortisol concentrations in a large population
      based field study.
AB  - OBJECTIVES: Longitudinal examinations of associations between daily stress,
      diurnal cortisol concentrations, and physiological parameters in population-based
      studies are needed. This study evaluates issues related to consent, collection,
      and protocol adherence for a low-burden saliva collection protocol. METHODS: In
      the 2007 pretest (n=193) for Wave IV of the National Longitudinal Study of
      Adolescent Health (Add Health) a three-sample, one-day, unsupervised saliva
      collection protocol was pilot tested. Embedded experiments allowed for
      examination of adherence and effects of monetary incentives. RESULTS: Although
      most (97%) study participants consented to collection, only about 80% actually
      mailed back samples. Use of a time-stamping TrackCap allowed comparison of self
      reported and stamp-recorded collection times. Of returned samples, self-report of
      collection time was missing for about a quarter, and only about one in three
      respondents (of those for whom adherence was calculable) fully adhered to the
      collection protocol, indicating significant potential for bias. Consent, return,
      and protocol adherence were unrelated to key sociodemographic characteristics,
      and did not improve with higher monetary incentives or knowledge of being
      monitored. CONCLUSIONS: Despite the relatively low-burden collection protocol and
      use of multiple strategies thought to improve collection and protocol adherence,
      response and adherence were poor, leading to a decision to drop cortisol
      measurement from the Wave IV Add Health protocol. Large field studies should
      carefully evaluate the feasibility of collection and protocol adherence for
      unsupervised collection protocols before implementing costly, and potentially
      unusable, biological measurements.

PMID- 21862226
TI  - Effects of intranasal oxytocin on social anxiety in males with fragile X
      syndrome.
AB  - Fragile X syndrome (FXS) is a rare inherited genetic disorder causing severe
      intellectual disability and autistic-like symptoms. Individuals with FXS, males
      in particular, often exhibit extreme eye gaze avoidance and hyperarousal when
      they encounter stressful social situations. We investigated whether oxytocin
      (OT), a hormone with prosocial and anxiolytic effects, could alleviate symptoms
      of social anxiety in this population. A randomized double-blind placebo
      controlled single-dose trial was performed with intranasal administration of
      placebo, 24 IU OT and 48 IU OT. Measures of eye gaze frequency, heart rate,
      respiratory sinus arrhythmia (RSA), heart rate variability (HRV) and salivary
      cortisol were obtained during a structured social challenge conducted 50 min
      following OT administration. Ten low-functioning males with FXS (aged 13-28
      years) traveled to Stanford for the initial visit: 8 completed the study. Eye
      gaze frequency improved significantly in response to the 24 IU OT dose and
      salivary cortisol levels decreased significantly in response to the 48 IU OT
      dose. There was no effect of OT on heart rate, RSA or HRV although individual
      plots of the heart rate data suggested that OT increased heart rate in some
      participants and decreased heart rate in others. These findings suggest that
      intranasal administration of OT may ameliorate some symptoms of social anxiety in
      patients with FXS. Further double-blind placebo-controlled studies of OT,
      conducted in combination with behavioral treatment programs, may be warranted.

PMID- 21862227
TI  - The Obsessive Compulsive Cocaine Scale: assessment of factor structure,
      reliability, and validity.
AB  - The present study assessed the factor structure, reliability, test retest,
      convergent validity, and predictive validity of the Obsessive Compulsive Cocaine
      Scale (OCCS), a newly developed questionnaire adapted from the Obsessive
      Compulsive Drinking Scale (OCDS). The questionnaire was administered to 189
      cocaine-dependent individuals participating in two medication treatment trials
      for cocaine dependence. Confirmatory factor analysis of this measure revealed
      that it primarily assesses two factors, obsessions and compulsions. In addition,
      the data provided strong support for the internal consistency, test-retest
      reliability, predictive validity, and convergent validity of this two-factor
      measure. Overall, the data provide support for the psychometric strength of a
      modified version of the OCDS specifically designed to assess obsessive and
      compulsive cocaine use among those with cocaine dependence.

PMID- 21862228
TI  - Influence of measurement setting and home smoking policy on smoking topography.
AB  - While cigarette puffing style, measured by smoking topography, is highly variable
      between individuals, smoking behavior or style tends to vary relatively little
      within individuals. Recent research has demonstrated that certain situational
      factors may produce variation in smoking topography, including location of
      smoking. Smoking topography directly observed by researchers in a laboratory may
      differ from that indirectly observed via portable measurement devices at
      participants' homes. The introduction of clean indoor air laws may also influence
      smokers' puffing styles, as smokers modify their smoking topography to ensure a
      quicker, more efficient smoking style. The goal of this analysis was to examine
      whether directly observed laboratory measures are representative of indirectly
      observed smoking behavior and to examine the influence of smokers' preference for
      indoor or outdoor home smoking on puffing style. Overall, participants smoked
      more intensively in the directly observed setting than when in the indirectly
      observed setting in terms of total volume intake, inter-puff interval, and total
      time spent smoking. This difference was most pronounced among individuals who
      reported smoking indoors when at home. The data suggest that adherence to an
      indoor home smoking policy may further influence an individual's smoking
      behavior.

PMID- 21862229
TI  - Drinking at college parties: examining the influence of student host-status and
      party-location.
AB  - The present research focuses on the party related drinking behaviors of college
      students and explores the differences in these behaviors based on students' host
      status (i.e. party host vs. party attendee). Furthermore, we examine if the
      differences in party hosts and attendees' drinking behaviors vary as a function
      of the party location (on-campus vs. off-campus). Multiple regression analyses
      were conducted using data from 3796 undergraduates at a Midwestern University.
      Findings revealed a significant interaction between host status and party
      location, such that student party hosts reported significantly greater drink
      consumption and related consequences as compared to party attendees, only when
      the party was organized off-campus. For parties organized on-campus, student
      hosts reported lower drink consumption as compared to attendees. College-based
      preventive interventions should target students likely to host off-campus parties
      due to their high risk for involvement in heavy drinking.

PMID- 21862230
TI  - Romantic attraction and adolescent smoking trajectories.
AB  - Research on sexual orientation and substance use has established that lesbian,
      gay, and bisexual (LGB) individuals are more likely to smoke than heterosexuals.
      This analysis furthers the examination of smoking behaviors across sexual
      orientation groups by describing how same- and opposite-sex romantic attraction,
      and changes in romantic attraction, are associated with distinct six-year
      developmental trajectories of smoking. The National Longitudinal Study of
      Adolescent Health dataset is used to test our hypotheses. Multinomial logistic
      regressions predicting smoking trajectory membership as a function of romantic
      attraction were separately estimated for men and women. Romantic attraction
      effects were found only for women. The change from self-reported heterosexual
      attraction to lesbian or bisexual attraction was more predictive of higher
      smoking trajectories than was a consistent lesbian or bisexual attraction, with
      potentially important differences between the smoking patterns of these two
      groups.

PMID- 21862231
TI  - Predictors of partying prior to bar attendance and subsequent BrAC.
AB  - Pre-drinking (e.g., pre-gaming, pre-loading) occurs frequently among young adult
      and college-aged drinkers and is associated with increased intoxication as well
      as alcohol-related problems. The purpose of the following study was to examine
      pre-drinking behaviors in situ, and to test whether drinking intentions mediate
      the relationship between heavy episodic drinking history and pre-drinking
      behaviors. We randomly selected a sample of 1040 young adults bar patrons at 32
      bars in a major metropolitan city in Southern California and asked participants
      to complete an interview concerning drinking behavior as well as provide a breath
      sample used to measure breath alcohol concentration. We used multilevel path
      analysis to test two meditational models. Results showed drinking intentions
      mediated the relationship between heavy episodic drinking history and pre
      drinking behavior as well as the relationship between heavy episodic drinking
      history and level of pre-drinking intoxication. Gender did not moderate these
      meditational relationships suggesting similar pre-drinking behaviors for both men
      and women. Potential methods to prevent pre-drinking behaviors in this population
      of young people are discussed.

PMID- 21862232
TI  - Augmentation of chemotherapy-triggered glioma cell apoptosis by blockade of
      arachidonic acid metabolism--the potential role of ceramide accumulation.
AB  - There has been recent interest in using cyclooxygenase-2 inhibitors in an effort
      to increase the efficacy of chemotherapy and/or radiation for treatment of
      malignant brain tumors. Although the mechanism is unclear, one result may be the
      accumulation of arachidonic acid (AA). AA is the key substrate for several
      biochemical pathways involved in the inflammatory cascade, including the
      cyclooxygenase (COX) enzymes. Cyclooxygenase-1 and cyclooxygenase-2 metabolize AA
      to produce prostaglandins and thromboxanes. Levels of these enzymes and their
      products are upregulated in gliomas, especially in malignant tumors. Likewise,
      the enzyme 5-lipoxygenase, also elevated in malignant gliomas, metabolizes AA to
      produce leukotrienes. Alternatively, enzymes of the cytochrome p450 family can
      metabolize AA to various products, some of which may aid glioma growth and
      angiogenesis. Unmetabolized AA activates the enzyme neutral sphingomyelinase,
      which produces ceramide, a second messenger and potent activator of apoptosis. It
      is hypothesized that simultaneous blockade of the COX, lipoxygenase, and/or
      cytochrome p450-mediated pathways would lead to greater accumulation of
      intracellular AA, resulting in elevated ceramide levels, thereby priming glioma
      cells for treatment-induced apoptotic cell death. Manipulation of AA/bioactive
      lipid metabolism, using readily available, well-tolerated medications may have
      the potential to increase the efficacy of currently used glioma treatments.

PMID- 21862233
TI  - The labelled-lines principle of the somatosensory physiology might explain the
      phantom limb phenomenon.
AB  - In the somatosensory system, various different sensory receptors capture
      different stimuli and convey them to the sensory cortex. Each type of receptor is
      specialised, that is, receives the stimulus to which it is predetermined to
      receive. Immediately as it is stimulated, the receptor sends a signal to the
      somatosensory cortex, via nerve fibres, and the area of the cortex that receives
      the signal determines the mode of the consequent perception. This mechanism is
      called principle of the "labelled" lines. The somatic receptors are the
      structures designated to receive stimuli, however, if their afferent fibres are
      stimulated at any point when approaching the cortex, the mode of perception by
      the cortex is the same as when the somatic receptor is stimulated directly. This
      occurs after the amputation of a limb, wherein the remaining fibres transmit to
      the cortex the mode of sensation for which they were specialised, despite the
      lack of somatic receptors at the beginning of the afferent pathway. However, the
      afferent pathway ends at the same cortex area as before the deafferentation.
      Since the somatic receptors and the integrity of afferent pathways are important
      to the regulation and modulation of the received stimuli, after the
      deafferentation the afferent pathway becomes anatomically and functionally
      abnormal. We believe these factors, involved in the pathophysiology of phantom
      limb (PHL), might be the explanation for this intriguing phenomenon.

PMID- 21862234
TI  - Nanocolloidal amorphous silica in drinking water as an autoimmunity trigger in
      Finland.
AB  - Previously, a curious observation was made that indicated high iodine
      concentrations in the raw (ground) water of a water treatment plant wells is
      associated with a high prevalence of autoimmune hypothyreosis in consumers. When
      fractionating this water with liquid chromatography (HPLC), iodine elutes in the
      same fractions as humic substances. Humic substances are determined by measuring
      light absorbance at 280 nm from the fractions. The prevalence of autoimmune
      hypothyreosis in the Finnish municipalities varies approximately ten fold. In
      Finland, water is distributed by the municipal water works, and every municipal
      water work has its own water source. Water sources in the municipalities with a
      high prevalence of autoimmune hypothyreosis are at least at times synclinal (the
      water flows from the flood lake to the aquifer). This kind of flood lake is a
      suitable environment for the synthesis of ternary system amorphous
      silica/humus/iodine nanocolloid (Asi/Hu/I) particles. According to our proposed
      hypothesis, Asi/Hu/I nanocolloid particles in tap water are internalised by
      thyrocytes via the sodium iodide symporter (NIS), indicating receptor-mediated
      endocytosis. Receptor-mediated endocytosis is quick and efficient so that enough
      amorphous silica nanoparticles are internalised inside thyrocytes to denature
      various intracellular proteins (e.g., thyroglobulin), thereby affecting the
      immunoreactivity of proteins, which triggers the autoimmunity process. In this
      article, we present observations that support this hypothesis.

PMID- 21862235
TI  - Reactive-homeostasis as a cybernetic model of the silhouette effect of denial of
      pregnancy.
AB  - In a woman presenting a pervasive denial of pregnancy, it happens that abdominal
      swelling is significantly reduced if not completely absent. In such cases, the
      announcement of the pregnancy to the unaware woman by a physician is often
      sufficient to trigger the spontaneous appearance of a normal silhouette of
      pregnancy with abdominal prominence. The pregnancy announcement acts as an input
      signal applied to the regulation mechanisms of the body with the consequence that
      the output signal; i.e. the silhouette of the pregnant woman; turns spontaneously
      from an abnormal shape to a normal one. By applying a system-based analysis to
      these observations, the brain appears clearly to be responsible for this disorder
      through instructions sent to the body by the nervous system. The silhouette
      effect is thus shown to be a cybernetic disorder as opposed to a functional one.
      The existence of unexpected information-and-semantic pathways throughout the
      human body is also revealed by this spontaneous transition. A reactive
      homeostasis model is then proposed in which symptoms result from an abnormal but
      coherent regulation of the functioning of the body caused by an unconscious
      mechanism by the brain to escape paradoxical realities. Spontaneous recovery is
      then a consequence of the paradoxical situation dissolution induced by the
      pregnancy announcement. This concept of reactive-homeostasis prompts us to
      investigate human disorders in complementary categories; i.e. cybernetic versus
      functional. Such an enlarged point of view may improve our knowledge of aetiology
      and suggest new perspectives for therapeutics research.

PMID- 21862236
TI  - Hypothesis: preeclampsia is a venous disease secondary to an increased intra
      abdominal pressure.
AB  - It is hypothesized that in some women an excessively high intra-abdominal
      pressure (IAP) compresses the inferior vena cava, uterine veins, portal vein,
      hepatic veins, splenic vein and renal veins which lead to a decreased flow in
      these vascular beds, producing lower extremity edema, fetal-placental ischemia, a
      glomerulopathy with proteinuria and hypertension, hepatic ischemia and
      thrombocytopenia, increased uric acid, and hemolysis/elevated liver enzymes/low
      platelet known as the HELLP syndrome. There can be variability in the expression
      of these components. Placental-fetal ischemia could lead to expression of soluble
      fms-like tyrosine kinase1 (sFLT) and endoglin which have been shown to cause
      additional diffuse endovascular damage. A further increase in IAP pushes the
      diaphragm cephalad, increasing intrathoracic pressure leading to upper extremity
      edema, decreased internal jugular venous flow, cerebral vascular engorgement,
      raised intracranial pressure, and if unresolved, seizures. Placental/fetal
      ischemia and hepatic ischemic necrosis may lead to diffuse inflammation and a
      septic inflammatory response syndrome (SIRS) which may become a vicious cycle,
      perpetuating the ischemia. It is further hypothesized that application of an
      externally applied negative abdominal pressure device will lower IAP and possibly
      reverse the pathophysiology of preeclampsia. As the abnormal placental proteins
      develop weeks before clinical preeclampsia, early application of external
      negative abdominal pressure may prevent development of the syndrome.

PMID- 21862237
TI  - mTORC1 activity as a determinant of cancer risk--rationalizing the cancer
      preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan
      diets.
AB  - Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin
      administration in transplant patients, and lifelong consumption of low-protein
      plant-based diets have all been linked to decreased risk for various cancers.
      These benefits may be mediated, at least in part, by down-regulated activity of
      the mTORC1 complex, a key regulator of protein translation. By boosting the
      effective availability of the translation initiator eIF4E, mTORC1 activity
      promotes the translation of a number of "weak" mRNAs that code for proteins,
      often up-regulated in cancer, that promote cellular proliferation, invasiveness,
      and angiogenesis, and that abet cancer promotion and chemoresistance by opposing
      apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly,
      may have utility not only for cancer prevention, but also for the treatment of
      many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in
      many cancers, strategies which target eIF4E directly--some of which are now being
      assessed clinically--may have the broadest efficacy in this regard. Many of the
      "weak" mRNAs coding for proteins that promote malignant behavior or
      chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which
      are active in a high proportion of cancers; thus, regimens concurrently targeting
      eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the
      transcriptional and translational levels, potentially achieving a very marked
      reduction in their expression.

PMID- 21862238
TI  - Acceptability of entire male pork with various levels of androstenone and skatole
      by consumers according to their sensitivity to androstenone.
AB  - Consumer acceptability of entire male pork at eating was assessed in three
      experiments. The 140 consumers involved in each experiment were classified as
      insensitive (INSENS) to the odor of pure androstenone or sensitive perceiving it
      as pleasant (SENS-PLEA) or unpleasant (SENS-UNPL). Entire male pork with very low
      skatole and androstenone levels (LS-LA) was as well accepted as gilt pork,
      whatever the consumer category. Entire male pork with elevated levels in both
      skatole and androstenone (HS-HA) was clearly differentiated from LS-LA pork by
      SENS-UNPL, but not by SENS-PLEA or INSENS consumers. Whatever the consumer
      category, entire male pork with elevated levels of androstenone and very low
      levels of skatole (LS-HA and LS-HHA) were not significantly differentiated from
      LS-LA pork. The results suggest that, in the conditions of the present
      experiment, androstenone and skatole totally explain boar taint at eating and
      that the acceptability threshold for androstenone, in the absence of skatole, is
      in the range of 2-3 MUg/g liquid fat.

PMID- 21862240
TI  - Chronic psychological and functional sequelae after emergent hand surgery.
AB  - PURPOSE: Several studies have shown that upper extremity trauma has serious,
      acute psychological effects after injury. This study's goal was to assess the
      psychological outcomes, including symptoms of major depression, posttraumatic
      stress disorder (PTSD), and other psychosocial variables, as well as the Quick
      Disabilities of the Arm, Shoulder, and Hand (QuickDASH) results, after severe
      hand trauma. We hypothesized that hand trauma would have persistent psychological
      sequelae long after the physical injury. METHODS: We performed a cross-sectional
      survey of 34 patients who had emergency hand surgery at a Level 1 trauma center
      an average of 16 months (range, 7-32 mo) earlier. The hand disability measure was
      the QuickDASH, and the psychological measures included the Center for
      Epidemiologic Studies Depression Scale, the Screen for Posttraumatic Stress
      Symptoms, the Medical Outcomes Study Social Support Survey Form, the Social
      Constraints Survey (to assess interpersonal stressors), and the Perceived Stress
      Scale. RESULTS: The overall QuickDASH score was 27. The mean score for PTSD was
      13 (above the clinical threshold for PTSD), and 29% of respondents had high
      levels of both depression and PTSD. High pain scores on the QuickDASH were
      strongly correlated with both depression and PTSD symptoms. CONCLUSIONS: This
      study found high levels of psychological distress in patients after hand trauma.
      Hand disability was strongly related to pain, depression, and PTSD symptoms. This
      study shows that the psychological sequelae of hand trauma can persist long after
      the physical injury. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 21862239
TI  - siRNA inhibition of aspartyl-asparaginyl beta-hydroxylase expression impairs cell
      motility, Notch signaling, and fetal growth.
AB  - Aspartyl-asparaginyl-beta-hydroxylase (AAH) regulates cell motility and
      invasiveness by enhancing Notch signaling. Invasive trophoblastic cells, which
      mediate placentation, normally express high levels of AAH. Previously, we showed
      that ethanol-impaired placentation is associated with reduced AAH expression. The
      present study determines the degree to which inhibition of AAH expression is
      sufficient to impair functions required for placentation. Immortalized, first
      trimester-derived, human trophoblastic cells (HTR-8/SVneo) were transfected with
      siRNA targeting AAH (siRNA-AAH) or no specific sequences (siRNA-Scr) using the
      Amaxa electroporation system. Directional motility was measured using an ATP
      luminescence-based assay. For in vivo studies, we microinjected siRNA-AAH or
      siRNA-Scr directly into the implantation sites (mesometrial triangle) of
      gestation-day-17, Long Evans pregnant rats, and harvested placentas 24 h later
      for histologic and molecular studies. siRNA-AAH transfection reduced AAH
      expression and directional motility in HTR-8/SVneo cells. In vivo delivery of
      siRNA-AAH reduced AAH expression and mean number of invasive trophoblastic cells
      at the implantation site. These adverse effects of siRNA-AAH were associated with
      impaired fetal growth and significantly reduced expression of Notch-signaling
      network genes. AAH is an important, positive regulator of trophoblastic cell
      motility, and inhibition of AAH in vivo leads to impaired implantation and fetal
      growth, and alters Notch-signaling mechanisms, similar to the effects of chronic
      ethanol exposure.

PMID- 21862241
TI  - Diversion and abuse of buprenorphine: findings from national surveys of treatment
      patients and physicians.
AB  - BACKGROUND: Since 2003, buprenorphine has been approved for the treatment of
      opioid dependence in office-based practice. Diversion and abuse can be a threat
      to its continued approval under these conditions. METHODS: As part of a national
      postmarketing surveillance program, applicants to substance abuse treatment and
      physicians certified to prescribe buprenorphine were surveyed about their
      perceptions of buprenorphine/naloxone diversion and abuse. These surveys were
      supplemented by information from national databases. Availability of
      buprenorphine/naloxone was measured by number of tablets dispensed. RESULTS:
      Measures of diversion and abuse of buprenorphine/naloxone increased from 2005 to
      2009. The results from the applicant survey showed that the perceptions of the
      extent of diversion and abuse were lower than positive controls, methadone,
      oxycodone and heroin, but higher than the negative control, amitriptyline. By
      2009, 46% of the physicians believed that buprenorphine/naloxone was diverted but
      44% believed illegal use was for self-management of withdrawal and 53% believed
      the source of the medication was substance abuse patients. Other measures from
      national databases showed similar results. When adjusted for millions of tablets
      sold per year, slopes for measures of diversion and abuse were reduced.
      CONCLUSIONS: The increases in diversion and abuse measures indicate the need to
      take active attempts to curb diversion and abuse as well as continuous monitoring
      and surveillance of all buprenorphine products. However, these increases parallel
      the increased number of tablets sold. Finding a balance of risk/benefit (i.e.
      diversion and abuse versus expanded treatment) remains a challenge.

PMID- 21862242
TI  - Application of the Enfer chemiluminescent multiplex ELISA system for the
      detection of Mycobacterium bovis infection in goats.
AB  - A study was conducted to optimise a multiplex serological immunoassay for use in
      identification of goats infected with Mycobacterium bovis. To assess assay
      specificity, 31 goats with a history of being free from M. bovis infection were
      used. To determine assay sensitivity, 180 Single Intradermal Comparative
      Tuberculin test (SICTT) positive goats were recruited. Additionally, 286 SICTT
      negative goats classed as potentially exposed animals present in the same
      positive herds were also included in the study. The results of the assay
      demonstrated a specificity of 100%. The multiplex assay detected 57/60 SICTT
      (95.0%) positive animals in one M. bovis infected herd and 120/120 (100%) in a
      second herd. In a separate experiment, 28 M. caprae culture confirmed infected
      goats from Spain were assayed, of which 24 (85.7%) were found positive in the
      test. The results show that inclusion of an antibody based assay can improve the
      ability to identify M. bovis and M. caprae infected goats. With further
      development and validation the multiplex assay may prove to be a useful tool for
      control of M. bovis and M. caprae infection in goats.

PMID- 21862243
TI  - Biophysical and microbiological study of high hydrostatic pressure inactivation
      of Bovine Viral Diarrheavirus type 1 on serum.
AB  - The effect of high hydrostatic pressure application on fetal bovine serum
      components and the model microorganism (Bovine Viral Diarrheavirus type 1 NADL
      strain) was studied at 132 and 220 MPa pressure for 5 min at 25 degrees C.
      Protein secondary structures were found to be unaffected by an artificial neural
      network application on the amide I region for both untreated and HHP treated
      samples. FTIR spectroscopy study of both the HHP-treated and control samples
      revealed changes in the intensity of some bands in the finger-print region (1500
      900 cm(-1)) originating mainly from lipids which are thought to result from
      changes in the lipoprotein structure. The virus strain lost its infectivity
      completely after 220 MPa HHP treatments. These results indicate that HHP can be
      successfully used for inactivation of pestiviruses while leaving structural and
      functional properties of serum and serum products unaffected.

PMID- 21862244
TI  - Moritella viscosa bypasses Atlantic salmon epidermal keratocyte clearing activity
      and might use skin surfaces as a port of infection.
AB  - Moritella viscosa is considered the main causative agent of winter ulcer disease
      in salmonid fish. In order to obtain more details on route of infection, we
      challenged Atlantic salmon (Salmo salar) epidermal keratocytes with M. viscosa
      and performed an Atlantic salmon immersion challenge. Although keratocytes were
      able to remove M. viscosa from surfaces, their engulfment capability appeared
      inefficient with reduced ability to reepithelialise superficial wounds (scale
      less skin surfaces) challenged with the bacterium. The immersion challenge
      revealed a significant connection between exposure area and mortality. Enhanced
      invasion ability and mortality was observed by M. viscosa exposure of the head
      and gill region compared to exposure of: the right side of the body; the left
      side of the body; or the body from pectoral to caudal fin (p=0.04). Ulcer
      development corresponded to area exposed (p=0.002), suggesting skin ulcer
      formation to result primarily from direct skin surface colonization. Ulceration
      of surfaces exposed to M. viscosa in parallel with occurrence of septicaemia
      suggests that both skin and gills may act as possible initiation sites for M.
      viscosa infections.

PMID- 21862245
TI  - Experimental infection of South American camelids with bluetongue virus serotype
      8.
AB  - Bluetongue (BT) is an infectious, non-contagious disease of wild and domestic
      ruminants. It is caused by bluetongue virus (BTV) and transmitted by Culicoides
      biting midges. Since 1998, BT has been emerging throughout Europe, threatening
      not only the naive ruminant population. Historically, South American camelids
      (SAC) were considered to be resistant to BT disease. However, recent fatalities
      related to BTV in captive SAC have raised questions about their role in BTV
      epidemiology. Data on the susceptibility of SAC to experimental infection with
      BTV serotype 8 (BTV-8) were collected in an animal experiment. Three alpacas
      (Vicugna pacos) and three llamas (Lama glama) were experimentally infected with
      BTV-8. They displayed very mild clinical signs. Seroconversion was first measured
      6-8 days after infection (dpi) by ELISA, and neutralising antibodies appeared 10
      13 dpi. BTV-8 RNA levels in blood were very low, and quickly cleared after
      seroconversion. However, spleens collected post-mortem were still positive for
      BTV RNA, over 71 days after the last detection in blood samples. Virus isolation
      was only possible from blood samples of two alpacas by inoculation of highly
      sensitive interferon alpha/beta receptor-deficient (IFNAR(-/-)) mice. An in vitro
      experiment demonstrated that significantly lower amounts of BTV-8 adsorb to SAC
      blood cells than to bovine blood cells. Although this experiment showed that SAC
      are generally susceptible to a BTV-8 infection, it indicates that these species
      play a negligible role in BTV epidemiology.

PMID- 21862246
TI  - Cognitive assessment of very preterm infants at 2-year corrected age: performance
      of the Italian version of the PARCA-R parent questionnaire.
AB  - BACKGROUND: Serial assessments of cognitive and language development are
      recommended for very preterm children, but standardized neuropsychological
      testing is time-consuming and expensive, as well as tiring for the child. AIMS:
      To validate the Italian version of the PARCA-R parent questionnaire and test its
      clinical effectiveness in assessing cognitive development of very preterm
      children at 2 years of corrected age. METHODS: 120 consecutive Italian very
      preterm children (mean gestational age 28.8 weeks, standard deviation 2.1) were
      assessed in four hospitals through the Mental Development Index (MDI) of the
      Bayley Scales of Infant Development (BSID-II). Parents completed the PARCA-R
      questionnaire, designed to measure children's non-verbal and verbal (vocabulary
      and sentence complexity) cognitive level. The correlation between the MDI and the
      PARCA-R Parent Report Composite (PRC) was tested through the Pearson correlation
      coefficient, and the receiver operating characteristic (ROC) curve was used to
      identify optimal PRC cut-offs. RESULTS: Significant correlation between the PRC
      score and MDI (r=0.60, p<0.001) indicated good concurrent validity. The area
      under the ROC curve was 0.83, and the cut-off of 46 lead to 72.7% sensitivity and
      77.1% specificity in identifying children with moderate/severe cognitive delay
      (MDI<70). Negative predictive value was 96.6 (90.3-99.3). Screening through PARCA
      R would reduce the number of children with MDI>=70 undergoing BSID-II or
      equivalent standardized tool from 109 to 25. CONCLUSIONS: The Italian version of
      PARCA-R retains good discriminative power for identifying cognitive delay in 2
      year very preterm children. It is well accepted by parents, and represents a
      valid and efficient alternative for developmental screening and outcome
      measurement.

PMID- 21862247
TI  - Bull sperm acrosome reaction induced by gamma-aminobutyric acid (GABA) is
      mediated by GABAergic receptors type A.
AB  - The effect of gamma-aminobutyric acid (GABA) on the bull sperm acrosome reaction
      was evaluated, and the interaction of progesterone, a physiologic inducer of the
      acrosome reaction, with the GABA receptor was explored. The acrosome reaction was
      stimulated by GABA in a dose-dependent manner. This effect was inhibited
      completely by bicuculline, a GABA A receptor antagonist, but GABA B and C
      receptor antagonists had no effect. Accordingly, muscimol, a GABA A receptor
      agonist, stimulated the acrosome reaction to the same extent as GABA, whereas
      baclofen (GABA B receptor agonist) and CACA (GABA C receptor agonist), had no
      effect. Preincubation with progesterone followed by the addition of GABA resulted
      in a significant increase in the percentage of acrosome reacted spermatozoa
      compared with progesterone or GABA alone. Taking into account that this increase
      was less than a simple addition of effects, it might be suggested that GABA and
      progesterone act through the same receptor and/or use the same mechanism of
      action. To test this hypothesis, the abilities of GABA and progesterone to induce
      acrosome reaction were tested in the presence of bicuculline, which suppressed
      both stimulatory effects. Given that the GABA A receptor is linked to the Cl(-)
      channel, we tested whether picrotoxin, a blocker of this channel, could modulate
      the effects of progesterone or GABA. Cl(-) channel blocker picrotoxin
      dramatically reduced the GABA and progesterone-initiated AR. IN CONCLUSION: GABA
      and progesterone stimulate the acrosome reaction in bull spermatozoa acting
      through a classical GABA A receptor. The mechanism of action requires the
      functional integrity of the Ca(2+) Cl(-) channel.

PMID- 21862248
TI  - Ultraviolet exposure and women's health.

PMID- 21862249
TI  - OMICS-strategies and methods in the fight against doping.
AB  - During the past decade OMICS-methods not only continued to have their impact on
      research strategies in life sciences and in particular molecular biology, but
      also started to be used for anti-doping control purposes. Research activities
      were mainly reasoned by the fact that several substances and methods, which were
      prohibited by the World Anti-Doping Agency (WADA), were or still are difficult to
      detect by direct methods. Transcriptomics, proteomics, and metabolomics in theory
      offer ideal platforms for the discovery of biomarkers for the indirect detection
      of the abuse of these substances and methods. Traditionally, the main focus of
      transcriptomics and proteomics projects has been on the prolonged detection of
      the misuse of human growth hormone (hGH), recombinant erythropoietin (rhEpo), and
      autologous blood transfusion. An additional benefit of the indirect or marker
      approach would also be that similarly acting substances might then be detected by
      a single method, without being forced to develop new direct detection methods for
      new but comparable prohibited substances (as has been the case, e.g. for the
      various forms of Epo analogs and biosimilars). While several non-OMICS-derived
      parameters for the indirect detection of doping are currently in use, for example
      the blood parameters of the hematological module of the athlete's biological
      passport, the outcome of most non-targeted OMICS-projects led to no direct
      application in routine doping control so far. The main reason is the inherent
      complexity of human transcriptomes, proteomes, and metabolomes and their inter
      individual variability. The article reviews previous and recent research projects
      and their results and discusses future strategies for a more efficient
      application of OMICS-methods in doping control.

PMID- 21862250
TI  - Postnatal ontogenesis of the tibia. Implications for age and sex estimation.
AB  - The growth of five variables of the tibia (diaphyseal length, diaphyseal length
      plus distal epiphysis, condylo-malleolar length, sagittal diameter of the
      proximal epiphysis, maximum breadth of the distal epiphysis) were analysed using
      polynomial regression in order to evaluate their significance and capacity for
      age and sex determination during and after growth. Data were collected from 181
      (90? and 91?) individuals ranging from birth to 25 years of age and belonging to
      three documented collections from Western Europe. Results indicate that all five
      variables exhibit linear behaviour during growth, which can be expressed by a
      first-degree polynomial function. Sexual significant differences were observed
      from age 15 onward in the two epiphysis measurements and condylo-malleolar
      length, suggesting that these three variables could be useful for sex
      determination in individuals older than 15 years. Strong correlation coefficients
      were identified between the five tibial variables and age. These results indicate
      that any of the studied tibial measurements is likely to serve as a useful source
      for estimating sub-adult age in both archaeological and forensic samples.

PMID- 21862251
TI  - Postmortem 24-h interval computed tomography findings on intrahepatic gas
      development and changes of liver parenchyma radiopacity.
AB  - PURPOSE: The purpose of this study was to assess and analyze the development of
      intrahepatic gas and its distribution over time as well as radiopacity changes of
      the liver parenchyma after non-traumatic death during a period of 24h using
      postmortem computed tomography (PMCT). MATERIALS AND METHODS: Five male corpses
      (age range 24-64 yrs) who had died for any other reason than trauma were enrolled
      in this study. Whole body multi detector row computed tomography (MDCT) scans
      (Brilliance 64-channel, Philips, Amsterdam, NL) were performed for 24 h with one
      examination per hour. At an average of 6h after the corpses were found on scene
      the first CT-exam took place. For the analysis of the intrahepatic gas
      development and distribution within 24h after death the liver was virtually
      divided into four parts. Each examination was analyzed for gas bubbles and the
      possible increase over time using a semiquantitative/visual assessment employing
      a four-grade scale. The changes of the radiopacity of the liver parenchyma were
      assessed in a similar way. In each of the four parts of the liver three regions
      of interest of the same size were placed and recorded over time. Three
      radiologists and one coroner independently performed the analysis of the gas
      development and radiopacity changes. RESULTS: In two corpses the amount of gas
      and its distribution did not change over the observation period whereas in the
      other three corpses the gas content increased within the first four to seven
      hours and was most pronounced in the left liver lobe and least in the right
      posterior liver lobe. In all five corpses the radiopacity of the liver parenchyma
      did not change significantly over time with the highest radiopacity in the right
      posterior liver lobe. Good interobserver reliability concerning the assessment of
      intrahepatic gas accumulation was found. DISCUSSION: Our results indicate that
      PMCT is useful to detect intrahepatic gas. However, several reasons for these
      findings besides putrefaction e.g. trauma, resuscitation exist. For an
      elucidation of the exact causation of the gas accumulation further studies are
      required with longer postmortem examination times (24-72 h) to detect more
      pronounced changes of gas and organ radiopacity but also an earlier start of
      examination after death is desirable. Moreover, it has to be elucidated whether
      other organs exhibit a similar behavior and how temperature of the CT-room and
      the body impacts on these parameters.

PMID- 21862252
TI  - DNA-based identification of a snake in a wine bottle using universal primers: a
      case of mistaken identity.

PMID- 21862253
TI  - Primary headache syndromes and sinus headache: An approach to diagnosis and
      management.
AB  - Chronic rhinosinusitis (CRS) and primary headache syndromes are common disease
      entities and headache and facial pain are common reasons for referral to
      otolaryngology units. Because of an association of nasal symptoms with primary
      headache syndromes and considerable similarities in their clinical presentations,
      primary headache syndromes may be misdiagnosed as sinus disease and vice versa.
      In this review we examine the evidence on which otolaryngologists can base
      clinical diagnosis and management and offer an approach to distinguishing these
      common clinical entities.

PMID- 21862254
TI  - Sclerosing sweat duct carcinoma of the nose with multiple cervical lymph node
      metastasis.
AB  - Sclerosing sweat duct carcinoma (SSDC) in the nose, a rare occurrence with no
      specific symptoms, is frequently confused with rhinophyma or other inflammatory
      disease. In this report, we describe a 64-year-old woman who presented with a
      mass on her nasal dorsum for 1 year. Initially, the tumor had been misdiagnosed
      as a rhinophyma and followed-up for 1 year. She was referred due to a persistent
      nasal and neck mass. Deep incisional biopsy was performed to produce sufficient
      tissue and the histopathologic results showed SSDC. We performed wide local
      excision and reconstruction using radial forearm musculocutaneous free flaps with
      a costal cartilage framework followed by bilateral neck dissection. SSDC is
      seldom recognized and is frequently clinically confused with benign syringoma
      prior to pathologic diagnosis. Wide and deep incisional biopsy is necessary for
      the correct diagnosis and successful treatment of SSDC.

PMID- 21862255
TI  - Otologic complications caused by hearing aid mold impression material.
AB  - We report two extremely rare cases of otologic complications caused by hearing
      aid mold impression material. The symptoms of patients with retained impression
      material are characteristic of the length of time the impression material is
      retained. In case 1 had a chronic discharge and granulation tissue of the middle
      ear, while case 2 presented with acute pain and dizziness. The management for
      retained impression material may require surgical interventions, which can be
      safely accomplished by standard otologic techniques.

PMID- 21862256
TI  - Transient low-tone air-bone gaps during convalescence immediately after canal
      plugging surgery for BPPV.
AB  - OBJECTIVES: The aim of the present study was to elucidate the time course and
      frequency patterns of transient low-tone air-bone gaps (ABGs) after canal
      plugging for intractable BPPV. METHODS: We investigated eight patients with
      intractable BPPV who underwent canal plugging. Four were cases with posterior
      type (pBPPV) and the other four were those with horizontal type (hBPPV). Pure
      tone audiometries (PTAs) were performed before and 7 days, 1 month and 6 months
      after surgery. ABGs (+) were defined as the three-tone-average >=20dB formulated
      by (a+b+c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1kHz, respectively.
      RESULTS: The ratio of the number of patients with ABGs (+) at the post-operative
      7th day and 1st month was 100.0% (8/8). The ratio at the post-operative 6th month
      was 0.0% (0/8). There were no significant differences in the time course or
      frequency patterns of the ABGs between pBPPV and hBPPV. CONCLUSIONS: We clearly
      demonstrated eight cases with intractable BPPV showing transient low-tone ABGs
      during convalescence immediately after canal plugging. During that period,
      patients also complained of motion-evoked dizziness. All these findings suggest
      that, during such a convalescence period, the plugged area might not be fixed yet
      and could still induce the dizziness and low-tone ABGs, as enlarged vestibular
      aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit low
      tone ABGs due to the third mobile inner ear window. More than one month after
      surgery, both the ABGs and dizziness could disappear according to fixation of the
      plugged area.

PMID- 21862257
TI  - Effect of the stapedotomy technique on early post-operative hearing results-
      Preliminary results.
AB  - OBJECTIVE: To compare three stapedotomy modalities used to fenestrate the stapes
      footplate in patients with primary otosclerosis. MATERIALS: The non-randomized
      and unblinded one-center study included 48 patients with primary otosclerosis who
      underwent stapes surgery between May 2008 and April 2009. The patients were
      divided into three groups (single shot and two-shot CO(2) laser stapedotomy,
      perforator) depending on the modality used for stapedotomy. Bone conduction (BC)
      and air conduction (AC) thresholds, air-bone gap (ABG), and the difference
      between mean pre-operative and 2- to 3-week post-operative BC thresholds were
      analyzed. RESULTS: The temporary BC deterioration was most pronounced at 6 and
      8kHz after 2-shot laser stapedotomy. A significant drop in AC or BC was not found
      in any of our 48 patients. Age, high-dose cortisone therapy, and 'preoperative
      hearing' did not influence the post-operative hearing results. CONCLUSION: Even
      though the number of patients presented here was small and statistical analysis
      was limited, the study showed a trend toward worse BC thresholds at 6 and 8kHz
      after a second shot CO(2) application. Whenever possible, treatment should avoid
      a second laser shot on the already opened inner ear with the laser parameters
      used for the initial shot.

PMID- 21862258
TI  - Management of laryngeal precancerous lesions.
AB  - OBJECTIVE: The identification of precancerous lesions is the basis of an early
      diagnosis, and of a treatment that allows, in the great part of cases, the
      preservation of organ functions. The aims of this study were: the evaluation of
      the less invasive treatment for precancerous lesion of the larynx to minimize the
      recurrences, the estimation of number of further operation required. METHODS: A
      prospective study was done on patients with clinical diagnosis of laryngeal
      precancerosis. The patients were treated by a transoral endoscopic approach with
      direct microlaryngoscopy (DML) doing an excision-biopsy with cold blade,
      consisting in excision of the whole visible lesion with vocal ligament
      preservation. RESULTS: A recurrence of a clinically evident precancerous lesion
      was present in 13.2% of patients that had a laryngeal intraepithelial lesion
      (LIN) 1 lesion and in 28.95% of patients that had a LIN 2 lesion. CONCLUSION: In
      order to achieve a control of a precancerous lesion, we suggest: excisional
      biopsy/subepithelial cordectomy (type 1 cordectomy) for LIN 1 lesions and
      subligament cordectomy (type 2 cordectomy) in case of LIN 2 cases. In case of
      recurrences of LIN 1 lesion we suggest directly a type 2 cordectomy.

PMID- 21862259
TI  - Surgical management of labyrinthine fistula in chronic otitis media with
      cholesteatoma.
AB  - OBJECTIVE: To present the surgical outcomes of complete removal of the matrix of
      labyrinthine fistulas in a large series of middle ear cholesteatomas. PATIENTS
      AND METHODS: This is a retrospective study. We analyzed 38 of 778 patients who
      were operated on for cholesteatoma and were proved to have labyrinthine fistula
      from 1991 to 2007. For this study, a more aggressive strategy was adopted that
      compromised immediate total removal of the matrix, regardless of size. To
      evaluate the safety and efficacy of the procedure, pre and postoperative pure
      tone audiometry were compared and the recurrence rate was analyzed. Relevant data
      from the literature using a wide array of strategies were compared with our
      results. RESULTS: Only two patients suffered from postoperative hearing
      deterioration of bone conduction of more than 10dB HL. There was no relationship
      between the size of labyrinthine fistulas and postoperative hearing
      deterioration. Recurrence of labyrinthine fistulas was not found. CONCLUSIONS:
      Total removal of the cholesteatoma matrix in one step is a safe and effective
      method for the treatment of labyrinthine fistulas.

PMID- 21862260
TI  - AICA syndrome with facial palsy following vertigo and acute sensorineural hearing
      loss.
AB  - We report a case of infarction of the anterior inferior cerebellar artery (AICA)
      with peripheral facial palsy following vertigo and acute sensorineural hearing
      loss. A 39-year-old female presented with vertigo and sudden hearing loss,
      tinnitus, and aural fullness of the right ear. An audiogram revealed a severe
      hearing loss at all tested frequencies in the right ear. Spontaneous nystagmus
      toward the left side was also observed. Otoneurological examinations showed
      sensorineural hearing loss of the right ear and horizontal and rotatory gaze
      nystagmus toward the left side, and a caloric reflex test demonstrated canal
      paresis. Initially, we diagnosed the patient for sudden deafness with vertigo.
      However, right peripheral facial palsy appeared 2 days later. An eye tracking
      test (ETT) and optokinetic pattern test (OKP) showed centralis abnormality. The
      patient's brain was examined by magnetic resonance imaging (MRI) and magnetic
      resonance angioglaphy (MRA) and showed an infarction localized in the pons and
      cerebellum. MRI and MRA revealed infarction of the right cerebellar hemisphere
      indicating occlusion of the AICA. Consequently, the patient was diagnosed with
      AICA syndrome but demonstrated regression following steroid and edaravone
      treatment. We suggest that performing MRI and MRA in the early stage of AICA
      syndrome is important for distinguishing cerebellar infarction resulting from
      vestibular disease.

PMID- 21862261
TI  - BRAFV600E mutation does not serve as a prognostic factor in Korean patients with
      papillary thyroid carcinoma.
AB  - OBJECTIVES: In recent years, BRAF(V600E) mutation has emerged as a promising
      prognostic marker for risk stratification of patients with papillary thyroid
      carcinoma (PTC). However, routine use of this marker has been questioned. In some
      parts of the world, particularly in Korea, the incidence of BRAF(V600E) mutation
      is too high to have true prognostic value. The relatively low number of tumors
      without BRAF(V600E) mutation would prejudice the efficient use of this marker in
      the Korean population. METHODS: The study involved 107 patients with
      histologically confirmed conventional PTC after surgical management for thyroid
      cancer from April 2010 to December 2010. BRAF(V600E) mutation analysis was
      performed by polymerase chain reaction (PCR)-based amplification of DNA extracted
      from paraffin-embedded tumor specimens, and the relationship between BRAF(V600E)
      mutation and various prognostic factors was investigated. RESULTS: BRAF(V600E)
      mutation was found to be present in 85 (79.4%) of 107 patients with conventional
      PTC. Analysis of the clinical characteristics as function of the presence or
      absence of BRAF(V600E) mutation revealed no differences between the BRAF(V600E)
      positive and BRAF(V600E)-negative patients. Moreover, BRAF(V600E) mutation was
      not correlated with any of the prognostic factors including age >=45 years, male
      gender, tumor size >=1cm, multifocality, extra-thyroidal extension, concurrent
      Hashimoto's thyroiditis, and lymph node metastasis neither in the univariate nor
      in the multivariate analysis. CONCLUSIONS: BRAF(V600E) mutation does not
      significantly reflect tumor aggressiveness in Korean patients with conventional
      PTC. We consider that BRAF(V600E) mutation does not possess prognostic value in
      Korea, where it is prevalent, and where most of the PTC types are conventional.

PMID- 21862262
TI  - Modulation of somatosensory abilities and the feeling of ear fullness in patients
      with acute sensorineural hearing loss.
AB  - OBJECTIVE: Patients with acute sensorineural hearing loss (ASNHL) often complain
      of a feeling of ear fullness (FEF) that is similar to the sensation experienced
      during barometric pressure changes. This suggests that modulation of
      somatosensory abilities may relate to the manifestation of FEF, whereas it cannot
      simply be assumed that somatosensory abilities would be directly affected by
      ASNHL. To examine this possible relationship, we estimated somatosensory
      abilities of the tympanic membrane, and investigated the relationship between
      them and the manifestation of FEF. METHODS: To estimate somatosensory abilities
      of the tympanic membrane, 83 new patients demonstrating unilateral sudden
      deafness were studied. The air pressure was loaded through an exclusive device on
      the external auditory canals in order to measure the minimum change in air
      pressure sensed by the subjects. The minimum pressure was defined as the minimum
      sensory threshold for air pressure loading (MSTAP; daPa). We estimated patient's
      somatosensory abilities and inquired about their experiences with FEF at the
      first medical examination (point 1) and at the time a steady audiogram was
      obtained (point 2). We also estimated MSTAP in 65 volunteers (130 ears) with no
      history of ear diseases and compared their MSTAP with that of sudden deafness
      patients. RESULTS: MSTAP values (-64.0+/-32.2daPa, 60.5+/-26.0daPa) on the
      affected side with both negative pressure and positive pressure measured at point
      1 were significantly higher than those (-40.7+/-15.0daPa, 40.0+/-12.7daPa)
      obtained at point 2 in all sudden deafness patients (p=0.0001, p=0.0001). There
      was no difference between MSTAP values (-39.6+/-10.7daPa, 39.9+/-11.4daPa) in
      normal subjects and those obtained at point 2 in all sudden deafness patients. On
      the other hand, significant differences of MSTAP with negative pressures between
      the affected and unaffected sides at point 1 were seen in 32 patients, and
      manifestation of FEF showed an insignificant association in these 32 patients
      (p<0.05). CONCLUSION: Modulation of somatosensory abilities in ASNHL seemed to be
      the best possible explanation for results, suggesting that a rise in MSTAP may
      somehow be associated with FEF. Although it cannot be verified by result of the
      current study, consideration of the previous literature suggests that the
      phenomenon may be caused by cross-modality of hearing and somatosensory
      abilities.

PMID- 21862263
TI  - Laryngeal schwannoma with extralaryngeal extension.
AB  - Schwannomas of the larynx are rare. Furthermore, a laryngeal schwannoma extending
      to the neck region is extremely rare. The present case report describes a 37-year
      old male patient with a history of hoarseness and cervical swelling on the left
      side for over 10 years. He presented with dyspnea on exertion. Fiberoptic
      laryngoscopy revealed a large submucosal mass in the left false and true vocal
      folds, and the left vocal fold was immobile. Magnetic resonance imaging revealed
      the presence of multiple tumors throughout the body, in addition to extension of
      the laryngeal tumor to the left neck region in a dumbbell shape. After analysis
      of the results of examinations including imaging tests and pathological
      examinations, a diagnosis of schwannomatosis was made. A tracheostomy was
      performed, along with resection of the laryngeal tumor. Following disarticulation
      of the cricothyroid joint and rotate ion of the thyroid cartilage, the
      intralaryngeal part of the tumor was smoothly removed without median or lateral
      thyrotomy. At the 3-month follow-up, the patient's vocal fold mobility was found
      to have recovered. Although uncommon, our procedure was very effective for the
      treatment of laryngeal schwannomas. By this approach, safe removal of the tumor
      was possible, without any injury to the laryngeal mucosa.

PMID- 21862264
TI  - Anti-microbial and therapeutic effects of modified Burow's solution on refractory
      otorrhea.
AB  - OBJECTIVE: Burow's solution, which contains 13% aluminum acetate, has been shown
      to be effective against chronic otitis media. Since the preparation of Burow's
      solution is time-consuming, its rapid preparation method has been recently
      developed. In this study, we evaluated the therapeutic effects of the modified
      Burow's solution on refractory otorrhea in patients with chronic suppurative
      otitis and its anti-microbial activity in vitro. METHODS: Fourteen ears of 12
      patients with chronic otitis media, granular myringitis, otitis externa and
      postoperative mastoid cavity problems were treated topically with cotton
      swab/ball soaked with modified Burow's solution or its four-fold diluted ear
      drops once a week. We then examined the antimicrobial spectrum of modified
      Burow's solution against clinical bacterial isolates from otorrhea and laboratory
      bacterial strains in vitro. RESULTS: In all ears, refractory otorrhea disappeared
      after 1-17 weeks treatment of modified Burow's solution with a mean of 5.4 weeks
      without apparent side-effects such as ototoxicity. Modified Burow's solution
      inactivated all Gram positive bacteria within 5min except Enterococcus species,
      all Gram negative bacteria including Pseudomonas aeruginosa within 30s and
      Candida albicans within 2min. In addition, modified Burow's solution inactivated
      MRSA completely within 5min, while 80.6% of MRSA survived even a 20-min contact
      with 0.3% ofloxacin. CONCLUSION: These findings indicate that modified Burow's
      solution, in addition to bearing a broad antimicrobial activity, is as effective
      as the original Burow's solution in the treatment of chronic suppurative otitis.

PMID- 21862265
TI  - Effects of dietary zinc deprivation on zinc concentration and ratio of apo/holo
      activities of angiotensin converting enzyme in serum of mice.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effects of dietary
      zinc deprivation on zinc concentration, the activity of angiotensin converting
      enzyme (ACE) and ratio of apo/holo-activities of ACE (ACE ratio) in the serum of
      mice. METHODS: Twenty-two male mice were deprived of dietary zinc for up to 9
      days. Zinc concentration in the serum was measured by means of atomic absorption
      spectrometry. Also, the activity of ACE in the serum was measured by HPLC as the
      activity of holo-ACE. After addition of zinc to the serum in vitro, the increase
      of ACE activity over the initial value was determined as that of apo-ACE.
      Finally, the ratio of apo/holo-ACE activities was calculated. RESULTS: There was
      a significant decrease of zinc concentration, but a slight decrease of the
      activity of ACE in the serum of mice by intake of zinc-deficient diet for 9 days.
      ACE ratio tended to increase on day 5 and was significantly increased on day 9 in
      mice deprived of dietary zinc. CONCLUSION: These findings suggest that ACE ratio
      is as sensitive as serum zinc concentration for the evaluation of zinc deficiency
      and can be used for the biochemical diagnosis of zinc nutritional status in
      patients with zinc deficiency-induced taste impairment.

PMID- 21862266
TI  - Does hyperandrogenism have an effect on hearing loss in patients with polycystic
      ovary syndrome?
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by
      chronic anovulation and hyperandrogenism. Hormonal changes can affect hearing
      loss and inner ear functions. We evaluated hearing loss with audiometric tests in
      young patients with PCOS. METHODS: Twenty-six women having PCOS and 25 normal
      individuals were enrolled in the study. Age ranges for PCOS and control groups
      were 20-35 years. Hormonal and biochemical values including LH, LH/FSH, E2,
      testosterone, fasting glucose and fasting insulin were calculated. Each subject
      was tested with low- (250-2000Hz) and high-frequency audiometry (4000-8000Hz).
      For each set of tests, mean values of air conduction at each frequency were
      measured for the PCOS and control groups and compared. RESULTS: No difference was
      observed in speech frequencies on audiologic tests between the groups, however
      high-frequency hearing loss were significantly higher (p<0.05) in PCOS patients
      than in control women. Also, hearing thresholds were normal range in all of
      frequencies in PCOS and control subjects. PCOS patients showed high levels of LH,
      LH/FSH, testosterone and fasting insulin. CONCLUSION: Our findings suggest that
      patients diagnosed with PCOS should be advised audiologic evaluation especially
      in the high frequency.

PMID- 21862267
TI  - Carcinoma cuniculatum mimicking leukoplakia of the mandibular gingiva.
AB  - Carcinoma cuniculatum (CC) is a rare variant of low-grade squamous cell carcinoma
      (SCC), and occurrence in the oral cavity is quite unusual. CC has a papillomatous
      keratinized surface like verrucous carcinoma, but CC has a propensity for
      aggressive local invasion, especially into the bone. Therefore, CC can be quite
      difficult to remove surgically. A 68-year-old man presented with a case of CC
      mimicking verrucous leukoplakia in the mandibular gingiva. Repeated biopsies
      showed no malignancy. Local resection was performed, and histological examination
      revealed the presence of well-differentiated SCC. Additional hemi-mandibulectomy
      was performed and the final histological diagnosis was CC. Local recurrence was
      detected at the 14-month follow-up examination. Chemotherapy with docetaxel was
      not effective, and he died of aspiration pneumonia. CC of the oral cavity is a
      rare entity and the diagnosis is hard to establish. Misdiagnosis could result in
      inadequate removal and local recurrence. Complete resection with a safety margin
      is essential because of the tendency for local invasion.

PMID- 21862268
TI  - Aggressive aneurysmal bone cyst of the maxilla confused with telangiectatic
      osteosarcoma.
AB  - Aneurysmal bone cyst (ABC) is a benign, expansile lesion typically affecting the
      long bones and vertebrae of patients younger than 20 years. Approximately 2% of
      ABCs occur in the head and neck region, most commonly affecting the mandible.
      Although the most common co-existing lesion associated with ABCs is the giant
      cell tumor, ABCs can be radiologically confused with telangiectatic osteosarcoma
      in cases of aggressive behavior and rapid growth. Here, we report a case of an
      aggressive ABC of the maxilla confused with telangiectatic osteosarcoma in a
      patient who underwent several operations for an osteoblastoma that was diagnosed
      histopathologically. This case highlights the need for a differential diagnosis
      both radiologically and histopathologically, because ABCs can easily be
      interpreted as a giant cell tumor or an osteoblastoma, and, on occasion, can be
      mistaken for osteogenic malignancies.

PMID- 21862269
TI  - Laryngeal morbidity after intubation with or without neuromuscular block in
      thyroid surgery using recurrent laryngeal nerve monitoring.
AB  - OBJECTIVE: The avoidance of neuromuscular blocking agents (NMBA) for endotracheal
      intubation is associated with a higher incidence of laryngeal discomfort and
      lesions, but could impair effectiveness of intra operative recurrent laryngeal
      nerve monitoring (IONM). METHODS: In a retrospective quality assessment study
      over a period of 30 months, a collective that had been intubated without NMBA was
      compared with a group, which had received NMBA. Endolaryngeal EMG was
      accomplished with a MagStim((r))-EMG-electrode. RESULTS: Out of the 127 patients
      with 224 nerves at risk (NAR; NMBA 102 NAR, no NMBA 122 NAR), more than 90%
      received a total intravenous anaesthesia with propofol, and 88% had remifentanil.
      Laryngeal side effects and damage scores did not differ significantly.
      CONCLUSIONS: In this special setting of IONM and thyroid surgery, avoidance of
      NMBA for endotracheal intubation seems not to increase the incidence of laryngeal
      side effects and lesions. If endotracheal intubation without NMBA is required,
      the authors suggest a standardized approach using induction agents as propofol
      and remifentanil.

PMID- 21862270
TI  - Laryngeal dysfunction and oral hygiene: Any relation?
AB  - OBJECTIVE: The purpose of this study is to establish a relation between poor oral
      hygiene and laryngeal dysfunction. METHODS: 43 adult patients were divided into
      two groups according to caries activity and oral hygiene. 18 patients with oral
      hygiene index score (OHI-S) 0-1 were grouped as the control group (good oral
      hygiene). 25 patients with OHI-S 2-3 were grouped as the study group (poor oral
      hygiene). Larygostroboscopic examination, aerodynamic measures by defining
      maximum phonation time (MPT) and s/z ratio and the pitch level measurements were
      done. Patients with gastroesophageal reflux disease (GERD), laryngopharyngeal
      reflux (LPR), previously confirmed laryngeal diseases or pathologies, systemic
      other diseases, or smokers were excluded from this study. RESULTS: The average
      MPT values of the study group were found to be statistically very significantly
      lower than those of the control group (p<0.01). In the stroboscopic findings, the
      proportion of normal closure levels were meaningfully higher in the control group
      than in the study group (p<0.05). The supraglottic involvement was found
      statistically meaningfully higher in the study group than in the control group
      (p<0.05). The proportion of normal closure phase incidences were meaningfully
      higher in the control group than in the study group (p<0.05). CONCLUSION: So, our
      findings of high glottic closure impairment, supraglottic involvement and low MPT
      scores in the poor oral hygiene group correlate with LPR findings such as muscle
      tension dysphonia. Poor oral hygiene may aggravate potential LPR in people.

PMID- 21862271
TI  - The interference of local over global information processing in children with
      attention deficit hyperactivity disorder of the inattentive type.
AB  - A classic finding in perception of compound patterns is normal individuals cannot
      skip global analysis in local-oriented processing, but they can successfully
      resist local analysis in global-oriented processing-the so-called global
      interference [1]. Recently, studies examining the role of brain hemisphere
      activity in the Navon task have indicated that the processing of global and local
      information can be, respectively, attributed to the right and left hemispheres.
      Moreover, many neuroimaging researches have revealed that certain core symptoms
      of attention deficit hyperactivity disorder (ADHD) are related to dysfunction of
      right hemisphere. These findings imply that global interference will be
      substantially less evident, and possibly even replaced by local interference in
      ADHD. The present study compared the performance of children with and without
      attention deficit hyperactivity disorder of the inattentive type (ADHD-I) in the
      processing of global and local information to examine the local interference
      hypothesis in ADHD. An ADHD-I group (n=15) and a paired control group (n=19)
      completed tasks using two versions of the Navon task, one requiring divided
      attention, in which no information was given to participants regarding the level
      at which a target would appear, and the other requiring selective attention, in
      which participants were instructed to attend to either the local or the global
      level. The results showed that children with ADHD-I exhibited local interference,
      regardless of which attention procedure was used. These results support the weak
      right hemisphere hypothesis in ADHD, and provide evidence against the deficit
      hypotheses for ADHD in the DSM-IV criteria [29], which postulates that
      inattention symptoms may manifest as a failure to provide close attention to
      details.

PMID- 21862272
TI  - Effects of a new postnatal stress model on monoaminergic neurotransmitters in rat
      brains.
AB  - INTRODUCTION: Stress and environmental perturbations influence postnatal brain
      development and may account for the high disability rates of preterm survivors
      following intensive care treatment. This study aims to investigate the impact of
      early environmental factors on the monoaminergic neurotransmitter system in the
      developing rat brain by using an innovative neonatal stress model. MATERIALS AND
      METHODS: After birth, in the experimental groups newborn rats were separated from
      their mothers and exposed to different stressful stimuli four times a day on day
      P0 to P6 for 10 min each. To mimic intensive care treatment, the stress protocol
      applied environmental factors like bright light, noise, and low temperature
      alternating with pain and handling stress at day- and night-time in a varying
      sequence. The non-stressed control mothers and litters were left completely
      undisturbed until sacrificing on day P7 or P20. RESULTS: Brains of stressed
      animals revealed significantly higher levels of norepinephrine (NE) and dopamine
      (DA) as determined by HPLC-ED and electrochemical detection at day P7 as compared
      to controls. When returned to their mothers' undisturbed care, juvenile rats at
      day P20 still showed higher (yet statistically not significant) concentrations of
      NE and DA in brain. The stressed animals gained less weight with significantly
      lower body weights at day P7 compared to controls. Their mothers developed
      various forms of stressed behaviour. CONCLUSIONS: A novel animal model for
      postnatal intensive care stress was established leading to changes in brain
      monoamine levels of newborn rats, while undisturbed maternal care seems to
      moderate the stress effects subsequently.

PMID- 21862273
TI  - Contrast-enhanced ultra-high-field liver MRI: a feasibility trial.
AB  - The aim of this study was to investigate the feasibility of dynamic contrast
      enhanced 7 T MRI of the liver using an eight-channel radiofrequency (RF)
      transmit/receive body-coil. 16 healthy subjects were examined on a 7 T MR system
      utilizing a custom-built eight-channel RF body-coil suitable for RF-shimming. The
      following data were acquired: (1) steady state free precession imaging, (2) T2w
      turbo spin echo imaging, (3) T1w in and opposed-phase imaging, (4) T1w 3D FLASH
      images pre-contrast and in arterial, portal-venous and venous phase and (5) a fat
      saturated pre- and post-contrast 2D FLASH sequence. Visual evaluation of (1) the
      delineation of liver vasculature, (2) the overall image quality, and (3) artifact
      presence and consequent image impairment was performed. SNR of the liver
      parenchyma was measured for the contrast-enhanced 2D and 3D FLASH sequences. For
      statistical analysis, a Wilcoxon-Rank Test was used. Best delineation of non
      enhanced liver vasculature and overall image quality was found for 2D FLASH MRI,
      with only slight improvement in vessel conspicuity after the application of
      contrast media. T2-weighted TSE imaging remained strongly impaired, falling short
      of diagnostic relevance and precluding a clinical application. Our results
      demonstrate the feasibility and diagnostic potential of dedicated contrast
      enhanced 7 T liver MRI as well as the potential for non-contrast-enhanced
      angiographic application.

PMID- 21862274
TI  - An academic-marketing collaborative to promote depression care: a tale of two
      cultures.
AB  - OBJECTIVES: Commercial advertising and patient education have separate
      theoretical underpinnings, approaches, and practitioners. This paper aims to
      describe a collaboration between academic researchers and a marketing firm
      working to produce demographically targeted public service anouncements (PSAs)
      designed to enhance depression care-seeking in primary care. METHODS: An
      interdisciplinary group of academic researchers contracted with a marketing firm
      in Rochester, NY to produce PSAs that would help patients with depressive
      symptoms engage more effectively with their primary care physicians (PCPs). The
      researchers brought perspectives derived from clinical experience and the social
      sciences and conducted empirical research using focus groups, conjoint analysis,
      and a population-based survey. Results were shared with the marketing firm, which
      produced four PSA variants targeted to gender and socioeconomic position.
      RESULTS: There was no simple, one-to-one relationship between research results
      and the form, content, or style of the PSAs. Instead, empirical findings served
      as a springboard for discussion and kept the creative process tethered to the
      experiences, attitudes, and opinions of actual patients. Reflecting research
      findings highlighting patients' struggles to recognize, label, and disclose
      depressive symptoms, the marketing firm generated communication objectives that
      emphasized: (a) educating the patient to consider and investigate the possibility
      of depression; (b) creating the belief that the PCP is interested in discussing
      depression and capable of offering helpful treatment; and (c) modelling different
      ways of communicating with physicians about depression. Before production, PSA
      prototypes were vetted with additional focus groups. The winning prototype,
      "Faces," involved a multi-ethnic montage of formerly depressed persons talking
      about how depression affected them and how they improved with treatment,
      punctuated by a physician who provided clinical information. A member of the
      academic team was present and consulted closely during production. Challenges
      included reconciling the marketing tradition of audience segmentation with the
      overall project goal of reaching as broad an audience as possible; integrating
      research findings across dimensions of words, images, music, and tone; and
      dealing with misunderstandings related to project scope and budget. CONCLUSION:
      Mixed methods research can usefully inform PSAs that incorporate patient
      perspectives and are produced to professional standards. However, tensions
      between the academic and commercial worlds exist and must be addressed. PRACTICE
      IMPLICATIONS: While rewarding, academic-marketing collaborations introduce
      tensions which must be addressed.

PMID- 21862275
TI  - Computerized continuing care support for alcohol and drug dependence: a
      preliminary analysis of usage and outcomes.
AB  - The central aim of this administrative data analysis was to examine usage of a
      Web-based disease management program designed to provide continuing recovery
      support to patients discharged from residential drug and alcohol treatment.
      Tailored clinical content was delivered in a multimedia format over the course of
      18 months posttreatment. The program also included access to a recovery coach
      across the 18 months. Consistent with other disease management programs, program
      usage decreased over time. A small subsample of patients accessed a large number
      of program modules in the year following treatment; these patients had
      significantly higher abstinence rates and consumed less alcohol than patients
      accessing few or no modules. Regression analyses revealed a significant
      relationship between the number of modules accessed and substance use outcomes in
      the year following treatment when controlling for motivation, self-efficacy, and
      pretreatment substance use. Limiting the analyses to only the more compliant
      patients did not reduce the magnitude of these effects. These preliminary results
      suggest that computerized support programs may be beneficial to patients recently
      treated for drug and alcohol issues. Methods to increase program engagement need
      additional study.

PMID- 21862276
TI  - Arthroscopic management of femoroacetabular impingement: minimum 2-year follow
      up.
AB  - PURPOSE: We report the results of arthroscopic management of femoroacetabular
      impingement with 2-year follow-up. METHODS: All patients undergoing hip
      arthroscopy were prospectively assessed with the modified Harris Hip Score.
      Arthroscopic correction of femoroacetabular impingement was first performed in
      2003. The cohort of this study consists of the first 100 consecutive cases that
      had achieved 2-year follow-up. RESULTS: There was 100% follow-up at 2 years. The
      mean age was 34 years (range, 13 to 76 years), with 67 male and 33 female
      patients. There were 63 cam, 18 pincer, and 19 combined lesions. Acetabular
      articular damage was found in 97 cases, femoral damage was present in 23, and
      there were 92 labral tears. The median improvement was 21.5 points, with 79 good
      and excellent results. No patient required revision to total hip arthroplasty,
      but 6 patients underwent a subsequent arthroscopic procedure. There were 3
      complications including a transient neurapraxia of the pudendal nerve and a
      transient neurapraxia of the lateral femoral cutaneous nerve, which resolved
      uneventfully, and 1 mild case of heterotopic ossification. CONCLUSIONS: We report
      favorable outcomes for the arthroscopic management of femoroacetabular
      impingement in our early experience in the first 100 consecutive cases. The high
      incidence of significant articular damage observed at the time of arthroscopic
      intervention is concerning.

PMID- 21862278
TI  - Evaluation of intra-articular mesenchymal stem cells to augment healing of
      microfractured chondral defects.
AB  - PURPOSE: This study evaluated intra-articular injection of bone marrow-derived
      mesenchymal stem cells (BMSCs) to augment healing with microfracture compared
      with microfracture alone. METHODS: Ten horses (aged 2.5 to 5 years) had 1-cm2
      defects arthroscopically created on both medial femoral condyles of the stifle
      joint (analogous to the human knee). Defects were debrided to subchondral bone
      followed by microfracture. One month later, 1 randomly selected medial
      femorotibial joint in each horse received an intra-articular injection of either
      20 * 10(6) BMSCs with 22 mg of hyaluronan or 22 mg of hyaluronan alone. Horses
      were confined for 4 months, with hand walking commencing at 2 weeks and then
      increasing in duration and intensity. At 4 months, horses were subjected to
      strenuous treadmill exercise simulating race training until completion of the
      study at 12 months. Horses underwent musculoskeletal and radiographic
      examinations bimonthly and second-look arthroscopy at 6 months. Horses were
      euthanized 12 months after the defects were made, and the affected joints
      underwent magnetic resonance imaging and gross, histologic, histomorphometric,
      immunohistochemical, and biochemical examinations. RESULTS: Although there was no
      evidence of any clinically significant improvement in the joints injected with
      BMSCs, arthroscopic and gross evaluation confirmed a significant increase in
      repair tissue firmness and a trend for better overall repair tissue quality
      (cumulative score of all arthroscopic and gross grading criteria) in BMSC-treated
      joints. Immunohistochemical analysis showed significantly greater levels of
      aggrecan in repair tissue treated with BMSC injection. There were no other
      significant treatment effects. CONCLUSIONS: Although there was no significant
      difference clinically or histologically in the 2 groups, this study confirms that
      intra-articular BMSCs enhance cartilage repair quality with increased aggrecan
      content and tissue firmness. CLINICAL RELEVANCE: Clinical use of BMSCs in
      conjunction with microfracture of cartilage defects may be potentially
      beneficial.

PMID- 21862277
TI  - The effect of platelet concentrates on graft maturation and graft-bone interface
      healing in anterior cruciate ligament reconstruction in human patients: a
      systematic review of controlled trials.
AB  - PURPOSE: To systematically review the current evidence for the effects of
      platelet concentrates on (1) graft maturation and (2) graft-bone interface
      healing in anterior cruciate ligament (ACL) reconstruction in human, controlled
      trials and for ensuing differences in clinical outcomes. METHODS: A systematic
      search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health
      Literature), Embase, Cochrane Central Register of Controlled Trials, and Cochrane
      Database of Systematic Reviews was performed for controlled trials of human ACL
      reconstruction with and without platelet concentrates. Data validity was
      assessed, and data were collected on graft maturation, graft-bone interface
      healing, and clinical outcome. RESULTS: Eight studies met the inclusion criteria.
      Seven studies reported on graft maturation with significantly better outcomes in
      the platelet groups in 4, and there were large differences in means in an
      additional 2 studies. Five studies reported on tunnel healing, and 4 found no
      difference between groups. Three studies assessed clinical outcome but found no
      differences, regardless of whether they had shown a beneficial effect (1 of 3) or
      no effect (2 of 3) of platelets on graft and tunnel healing. CONCLUSIONS: The
      current best evidence suggests that the addition of platelet concentrates to ACL
      reconstruction may have a beneficial effect on graft maturation and could improve
      it by 20% to 30% on average, but with substantial variability. The most likely
      mode of action is that treatment with platelets accelerates graft repopulation
      and remodeling, and this interpretation is supported by the existing data and is
      biologically plausible. However, the current evidence also shows only a very
      limited influence of platelet concentrates on graft-bone interface healing and no
      significant difference in clinical outcomes. LEVEL OF EVIDENCE: Level III,
      systematic review of Level I, II, and III studies.

PMID- 21862279
TI  - [Anaesthesia for caesarean section in a pregnant woman with cor triatriatum].
AB  - A 41-year-old woman suffering from a left cor triatrium, pregnant for the first
      time, was hospitalized for a caesarean section in the context of a pulmonary
      arterial hypertension with severe anaemia. The anaesthetic strategy which was
      decided on involved setting up a haemodynamic monitoring prior to induction of a
      general anaesthetia with etomidate, remifentanil and succinylcholine and
      maintained with propofol, sufentanil and cisatracurium. This strategy allowed the
      hemodynamic to be stabilized during the operation. The improvement of the
      arterial pulmonary hypertension immediately after coming out of the operating
      theatre allowed the patient to be briefly monitored in the intensive care unit
      and to be allowed home on the 10th day following the operation. The patient's
      cardiopathy was corrected in the 5th month after the birth.

PMID- 21862280
TI  - Coronary artery perforation during percutaneous coronary intervention: a
      systematic review and meta-analysis.
AB  - Numerous studies have examined the incidence, predictors, outcomes, and
      management strategies of coronary artery perforation (CAP). Individually, these
      studies have been inconclusive because of their limited sample sizes and/or
      single-centre designs. We conducted a systematic review and meta-analysis of
      studies pertaining to CAP in order to estimate its incidence and outcomes and to
      critically review its risk factors and treatment. We systematically searched the
      literature to identify all registry studies investigating CAP. Data were pooled
      by means of the random-effects model. In 16 studies involving 197,061
      percutaneous coronary interventions, the pooled incidence of CAP was 0.43% (95%
      confidence interval, 0.35%-0.52%). The most reproducible risk factors were
      treatment of complex lesions and use of atheroablative devices. A variety of
      major management strategies for CAP were used, in particular, observation,
      heparin reversal, prolonged balloon inflation, covered stent implantation,
      pericardiocentesis, and surgery. In a hierarchical Bayesian random-effects model,
      the pooled tamponade rates were 0.4% (95% credible interval [CrI], 0.0%-5.7%),
      3.3% (95% CrI, 0.0%-11.4%), and 45.7% (95% CrI, 34.9%-57.5%) for patients with
      Ellis class I, II, and III CAP, respectively. Pooled mortality rates were 0.3%
      (95% CrI, 0.0%-4.4%), 0.4% (95% CrI, 0.0%-2.8%), and 21.2% (95% CrI, 12.0%-31.4%)
      for patients with Ellis class I, II, and III CAP respectively. CAP complicating
      percutaneous coronary intervention is rare, and its morbidity and mortality vary
      directly with Ellis classification. Management discrepancies highlight the need
      to establish a uniform treatment paradigm for CAP.

PMID- 21862281
TI  - Identifying empirically supported treatments for pica in individuals with
      intellectual disabilities.
AB  - The purpose of the current study was to critically examine the existing
      literature on the treatment of pica displayed by individuals with intellectual
      disabilities. Criteria for empirically supported treatments as described by
      Divisions 12 and 16 of APA, and adapted for studies employing single-case designs
      were used to review this body of literature. A total of 34 treatment studies were
      identified, 25 of which were well designed and reported at least an 80% reduction
      in pica (21 studies reported 90% or greater reduction in pica). Results indicated
      that behavioral treatments in general, and treatments involving the combination
      of reinforcement and response reduction procedures in particular, can be
      designated as well-established treatments for pica exhibited by individuals with
      intellectual disabilities.

PMID- 21862282
TI  - IQ predicts word decoding skills in populations with intellectual disabilities.
AB  - This is a study of word decoding in adolescents with Down syndrome and in
      adolescents with Intellectual Deficits of unknown etiology. It was designed as a
      replication of studies of word decoding in English speaking and in Hebrew
      speaking adolescents with Williams syndrome (Levy & Antebi, 2004; Levy, Smith, &
      Tager-Flusberg, 2003). Participants' IQ was matched to IQ in the groups with
      Williams syndrome and was within the range of mental retardation or borderline
      intelligence. Our aim was to investigate the impact of IQ on word decoding in
      these populations, rather than estimate their overall reading level. Similar to
      the results seen in people with Williams syndrome, word decoding was correlated
      with auditory short term memory and with phonological awareness tasks yet these
      correlations were mediated by IQ. It is argued that learning to decode is an
      explicit task that relies primarily on general cognitive resources of the kind
      that are most vulnerable in people with sub-normal IQ.

PMID- 21862283
TI  - Three-dimensional upper limb movement characteristics in children with hemiplegic
      cerebral palsy and typically developing children.
AB  - The aim of this study was to measure which three-dimensional spatiotemporal and
      kinematic parameters differentiate upper limb movement characteristics in
      children with hemiplegic cerebral palsy (HCP) from those in typically developing
      children (TDC), during various clinically relevant tasks. We used a standardized
      protocol containing three reach tasks (forwards, upwards, and sideways), two
      reach-to-grasp tasks (with objects requiring different hand orientations), and
      three gross motor tasks. Spatiotemporal (movement duration, trajectory
      straightness, maximum velocity, and timing of maximum velocity), as well as
      kinematic parameters (discrete angles and waveforms of the trunk, scapula,
      shoulder, elbow and wrist), were compared between 20 children with HCP (age 10.9
      +/- 2.9 years) and 20 individually age-matched TDC (age 10.9 +/- 3.0 years).
      Kinematic calculations followed the recommendations from the International
      Society of Biomechanics. Results showed that children with HCP had longer
      movement durations, less straight hand trajectories, and lower maximum velocities
      compared to the TDC. Timing of maximum velocity did not differ between both
      groups. The movement pathology in children with HCP was highlighted by increased
      trunk movements and reduced shoulder elevation during reaching and reach-to
      grasp. We also measured an increased anterior tilting and protraction of the
      scapula in children with HCP, although differences were not significant for all
      tasks. Finally, compared to the TDC, children with HCP used less elbow extension
      and supination and more wrist flexion to execute all tasks. This study reported
      distinct 3D upper limb movement characteristics in children with HCP and age
      matched TDC, establishing the discriminative ability of the measurement
      procedure. From a clinical perspective, combining spatiotemporal and kinematic
      parameters may facilitate the identification of the pathological movement
      patterns seen in children with HCP and thereby add to a well-targeted upper limb
      treatment planning.

PMID- 21862284
TI  - Symptoms of psychopathology in adults with intellectual disability and seizures.
AB  - Seizures are more common in individuals with intellectual disabilities than in
      the general population. As a result, differences in functioning for individuals
      with intellectual disability with and without seizures have been evaluated.
      Research on differences in psychopathology for individuals with intellectual
      disability with and without seizures has been mixed. The purpose of this study
      was to examine differences in subscale scores on the Diagnostic Assessment for
      the Severely Handicapped-II (DASH-II) between individuals with intellectual
      disability with and without seizures. In this study, 321 individuals from two
      large developmental centers in the southeastern United States were administered
      the DASH-II. Researchers found that the seizure group endorsed significantly more
      symptoms on the mood subscale than the group without seizures. No other group
      differences were found to be significant. Implications of these results are
      discussed.

PMID- 21862285
TI  - Adaptive behavior of primary school students with visual impairments: the impact
      of educational settings.
AB  - This study explored the adaptive behavior of primary school students with visual
      impairments, as well as the impact of educational setting on their adaptive
      behavior. Instrumentation included an informal questionnaire and the Vineland
      Adaptive Behavior Scales. Participants were 36 primary school students with
      visual impairments. The educational setting had an effect on Daily Living Skills
      and Socialization. Students with visual impairments visiting special schools
      present worse adaptive behavior (higher developmental delay) compared to students
      visiting mainstream schools. Moreover, the educational level of parents
      influences the developmental delay on the Communication and Socialization. The
      higher the educational level of parents the lower the developmental delay.

PMID- 21862286
TI  - A kernel-based perceptron with dynamic memory.
AB  - In this study, we propose a dynamical memory strategy to efficiently control the
      size of the support set in a kernel-based Perceptron learning algorithm. The
      method consists of two operations, namely, the incremental and decremental
      projections. In the incremental projection, a new presented instance is either
      added to the support set or discarded depending on a predefined rule. To diminish
      information loss, we do not throw away those discarded examples cheaply, instead
      their impact to the discriminative function is sustained by a projection
      technique, which maps the modified discriminative function into the space spanned
      by the original support set. When a new example is added to the support set, the
      algorithm moves to the decremental projection. We evaluate the minimum
      information loss by deleting one instance from the support set. If this minimum
      information loss is less than a tolerable threshold, then the corresponding
      instance is removed, however, its contribution to the discriminative function is
      reserved by the projection technique. By this, our method can on one hand keep a
      relatively small size of the support set and on the other hand achieve a high
      classification accuracy. We also develop a method which sets a budget for the
      size of the support set. We test our approaches to four benchmark data sets, and
      find that our methods outperform others in either having higher classification
      accuracies when the sizes of their support sets are comparable or having smaller
      sizes of the support sets when their classification accuracies are similar.

PMID- 21862287
TI  - Autonomy support in primary care--validation of the German version of the Health
      Care Climate Questionnaire.
AB  - OBJECTIVES: There is a growing need for studies to measure how patients feel
      supported in their autonomy. The Health Care Climate Questionnaire (HCCQ) is an
      instrument to assess the physician's support to motivate the patient to take
      personal responsibility for his/her health. The aim of this study was to
      translate the HCCQ into German and validate the translated version, called the
      HCCQ-Deutschland (HCCQ-D). STUDY DESIGN AND SETTING: In a cross-sectional study,
      we translated and culturally adapted the HCCQ, then administered the
      questionnaire to primary care patients from nine general practices in Germany. We
      used the European Task Force on Patient Evaluations of General Practice
      questionnaire (EUROPEP) to assess convergent validity. Subsequently, we performed
      Cronbach alpha to assess internal consistency and exploratory factor analysis to
      evaluate the underlying factor structure of the items. RESULTS: Of 450
      questionnaires, we included 351 (78%) in the final analysis. Internal consistency
      was high, with Cronbach alpha=0.97. We found one major underlying factor similar
      to the English version: all items showed a scale correlation above 0.7. The mean
      values of the HCCQ correlated moderately (-0.5) with those of the EUROPEP.
      CONCLUSION: This study shows similar psychometric properties of the HCCQ-D as of
      the original English instrument. The HCCQ-D may be appropriate to explore German
      speaking patients' perceived autonomy support in primary care settings.

PMID- 21862288
TI  - A fully automated trabecular bone structural analysis tool based on T2* -weighted
      magnetic resonance imaging.
AB  - One major source affecting the precision of bone structure analysis in
      quantitative magnetic resonance imaging (qMRI) is inter- and intraoperator
      variability, inherent in delineating and tracing regions of interest along
      longitudinal studies. In this paper an automated analysis tool, featuring bone
      marrow segmentation, region of interest generation, and characterization of
      cancellous bone of articular joints is presented. In evaluation studies conducted
      at the knee joint the novel analysis tool significantly decreased the standard
      error of measurement and improved the sensitivity in detecting minor structural
      changes. It further eliminated the need of time-consuming user interaction, and
      thereby increasing reproducibility.

PMID- 21862289
TI  - The spatial location of the mandibular canal in Chinese: a CT study.
AB  - The inferior alveolar nerve (IAN) is vulnerable to injury from mandible fractures
      and surgical procedures so anatomical variations of IAN are important.
      Postoperative sensory alteration of the lip and chin region is high after
      mandibular orthognathic surgery. The incidence of IAN paresthesia following
      sagittal split ramus osteotomy (SSRO) ranges from 54% to 86% at 4-8 days, 41 to
      75% at 1 month, 33 to 66% at 3 months, 17 to 58% at 6 months and 15 to 33% at 1
      year postoperatively. This study determined the anatomical position of the
      mandibular canal in relation to cortical bone and molar teeth in Chinese using
      archived CT records. The mandibular canal was the farthest from the buccal cortex
      at the second molar region (mean 6.79mm; minimum distance 4.80mm). The anatomical
      location of the mandibular canal in local Chinese compares with studies on Asian
      cadavers. The mandible body was thickest in the region of the second molar
      (11.9mm). The vertical buccal cut for SSRO should be in the region of the
      mandibular second molar where the bone is thickest and the mandibular canal is
      furthest from the buccal cortex. The safe depth for the vertical buccal cut is
      4.8mm (minimum horizontal distance).

PMID- 21862290
TI  - Predictive importance of left ventricular myocardial stiffness for the prognosis
      of patients with congestive heart failure.
AB  - OBJECTIVES: This study was designed to determine the prognostic importance of
      left ventricular (LV) myocardial stiffness, a hemodynamic index which is closely
      related to B-type natriuretic peptide (BNP) concentration in patients with
      congestive heart failure (CHF). BACKGROUND: While elevated BNP, an abnormality of
      cardiac neurohormones, is known to be an independent marker of death or re
      admission, it remains to be clarified whether there is also a strong predictor
      directly related to cardiac dysfunction. METHODS: LV performance variables and
      stress-strain analyses including diastolic myocardial stiffness constant (K(m))
      were obtained from 37 patients with initial CHF by the combined simultaneous
      measurement of echocardiographic and hemodynamic data. Survivors were monitored
      for a mean of 23 months, with the main endpoint being combined death or first re
      admission for CHF. RESULTS: Ten patients (27%) were primary endpoint cases. Both
      K(m) and plasma BNP levels were higher in the event than in the event-free group.
      By Cox proportional hazards analysis, K(m)>=4.0 was identified as the only
      variable with significant and independently incremental predictive power to
      affect the primary endpoint (adjusted hazard ratio=7.354, 95% confidence interval
      1.379-39.232, p=0.02). CONCLUSIONS: In patients with CHF, increased myocardial
      stiffness may have greater prognostic significance compared to other conventional
      predictors. Increased myocardial stiffness may be considered to be an important
      prognostic factor independent of the loading conditions.

PMID- 21862291
TI  - Relationship between clinical outcomes and unintentional pulmonary vein isolation
      during substrate ablation of atrial fibrillation guided solely by complex
      fractionated atrial electrogram mapping.
AB  - BACKGROUND: Controversy exists as to whether atrial fibrillation (AF) ablation
      guided solely by complex fractionated atrial electrogram (CFAE) has a good
      outcome despite not requiring pulmonary vein isolation (PVI). OBJECTIVES: The
      purpose of this study was to evaluate the effectiveness of AF ablation guided
      solely by targeting CFAE areas, and to determine whether its clinical efficacy
      has any relationship with unintentionally isolating the PV. METHODS: We studied
      100 consecutive patients (ages 59 +/- 11 years; 54 with paroxysmal, 35
      persistent, and 11 long-standing persistent AF), who underwent CFAE-ablation. PV
      potential (PVP) was recorded before and after ablation. After excluding 39
      patients in whom sinus rhythm could not be maintained before ablation by internal
      cardioversion and/or who had a history of PVI(s), PVPs were analyzed. RESULTS: AF
      was terminated during ablation in 98% of paroxysmal, 80% of persistent, and 55%
      of long-standing persistent AF patients. Nifekalant (0.3-0.6 mg/kg) was
      administered in 30%, 57%, and 83%, respectively. The common areas of CFAE around
      the PVs were anterior to the right PVs, posterior to the left PVs, and at the
      ridge of the left atrial appendage. Among 215 PVs in 61 patients (42 paroxysmal,
      19 persistent), only 17 PVs (8%) were unintentionally isolated. The atrial
      potential to PVP was prolonged (>30 ms) in 13% of PVs. After at least 12 months
      of follow-up (23 +/- 5 months), 65% of paroxysmal (11% with drug), 54% of
      persistent (37% with drug), and 45% of long-standing (60% with drug) AF patients
      were free from atrial arrhythmia after one session. CONCLUSIONS: CFAE-ablation
      terminates AF without isolating PVs in a high percentage of patients, and yields
      excellent clinical outcomes.

PMID- 21862292
TI  - Damage at the root of cell renewal--UV sensitivity of human epidermal stem cells.
AB  - BACKGROUND: The epidermis harbors adult stem cells that reside in the basal layer
      and ensure the continuous maintenance of tissue homeostasis. Various studies
      imply that stem cells generally possess specific defense mechanisms against
      several forms of exogenous stress factors. As sun exposition is the most
      prevalent impact on human skin, this feature would be of particular importance in
      terms of sensitivity to UV-induced DNA damage. OBJECTIVE: To investigate whether
      human epidermal stem cells are susceptible to UV-induced DNA damage and
      subsequent functional impairment. METHODS: A method to isolate human epidermal
      stem cells from suction blister epidermis was established and validated.
      Volunteers were treated with solar-simulated irradiation on test areas of the
      forearm and stem cells were isolated from suction blister material of this
      region. DNA damage was analyzed by staining for cyclobutane thymidine dimers. The
      functional consequences of UV-induced damages were assessed by colony forming
      efficiency assays and gene expression analyses. RESULTS: Compared to an
      unirradiated control, stem cells isolated from areas that were exposed to solar
      simulated radiation showed significantly more DNA lesions. Although the number of
      stem cells was not reduced by this treatment, a functional impairment of stem
      cells could be shown by reduced colony forming efficiency and altered gene
      expression of stem cell markers. CONCLUSIONS: Despite their essential role in
      skin maintenance, epidermal stem cells are sensitive to physiological doses of UV
      irradiation in vivo.

PMID- 21862293
TI  - Studies on pectin coating of liposomes for drug delivery.
AB  - The present study investigated the surface coating of charged liposomes by three
      different types of pectin (LM, HM and amidated pectin) by particle size
      determinations and zeta potential measurements. The pectins and the pectin coated
      liposomes were visualized by atomic force microscopy. The adsorption of pectin
      onto positive liposomes yielded a reproducible increase in particle size and a
      shift of the zeta potential from positive to negative side for all three pectin
      types, whereas the adsorption of pectin onto negative liposomes did not render
      any significant changes probably due to electrostatic repulsion. The positive
      liposomes coated with HM-pectin gave the largest pectin coated particles with the
      least negative zeta potential, while the opposite was observed for the LM-pectin
      coated positive liposomes. Furthermore, results from dynamic light scattering
      revealed narrow size distributions, indicating that the degree of aggregation was
      low for the pectin coated liposomes. As liposomes are able to encapsulate drugs
      and pectin has been found to be mucoadhesive, these pectin coated liposomes may
      be potential drug delivery systems.

PMID- 21862294
TI  - Electrochemically induced anatase inhibits bacterial colonization on Titanium
      Grade 2 and Ti6Al4V alloy for dental and orthopedic devices.
AB  - Bacterial contamination of implanted devices is a common cause of their failure.
      The aim of the present study was to assess the capability of electrochemical
      procedures to: (a) promote the formation of anatase on the surface of
      commercially pure Grade 2 Ti and Ti Grade 5 (Ti6Al4V) alloy; (b) inhibit in vitro
      biofilm formation of Staphylococcus aureus, Staphylococcus epidermidis,
      Streptococcus mutans and Porphyromonas gingivalis and oral plaque in vivo, (c)
      preserve favorable response of osteoblasts and fibroblasts to materials surfaces.
      Ti Grade 2 and Ti Grade 5 were respectively anodized at two different voltages:
      90 and 130V for pure titanium; 100 and 120V for Ti6Al4V alloy. Surface
      characterization was performed by scanning electron microscopy (SEM) equipped
      with EDS probe, laser profilometry and X-ray diffractometry. Bacterial adhesion
      characterization was performed either in vitro and in vivo in patients.
      Osteoblast and fibroblast response was evaluated by metabolic activity
      assessment. The higher voltage applied in the anodization treatment of pure
      titanium (130V) and Ti6Al4V alloy (120V) surfaces, compared to the untreated pure
      titanium and Ti6Al4V and to lower voltage treatments, resulted in a greater
      decrease in bacterial attachment and biofilm formation in both in vitro and in
      vivo experiments. In contrast, the high voltage treatments were found to promote
      osteoblasts and fibroblasts proliferation. The observations indicated that the
      experimented high voltage anodization treatments may contribute to preserve the
      tissue integration and reduce bacteria colonization of titanium and titanium
      alloy for implantable applications.

PMID- 21862295
TI  - Edelfosine disturbs the sphingomyelin-cholesterol model membrane system in a
      cholesterol-dependent way - the Langmuir monolayer study.
AB  - Synthetic alkyl-lysophospholipids, represented by edelfosine (ED), reveal strong
      anticancer activity and therefore are promising drugs used in anticancer therapy.
      Primary target for edelfosine is cellular membrane, which is in contrast to
      traditional cytostatics affecting DNA. The mechanism of antitumor activity of
      edelfosine was hypothesized to be related to its accumulation in membrane rafts.
      Inspired by these findings, we have performed the Langmuir monolayer studies on
      the influence of edelfosine on systems composed of sphingomyelin (SM) and
      cholesterol (Chol), being the principal components of membrane rafts.
      Sphingomyelin-cholesterol proportion in monolayers was varied to reflect the
      composition of solely membrane rafts (SM/Chol=2:1) and contain excess of
      cholesterol (SM/Chol=1:1 and 1:2). Into these systems, edelfosine was added in
      various concentrations. The analysis of surface pressure-area isotherms,
      complemented with films visualization with Brewster angle microscopy (BAM)
      allowed us to compare the effect of edelfosine on condensation and ordering of
      SM/Chol monolayers. The results evidenced that the influence of ED on the
      interactions in model membranes and its fluidizing effect is highly cholesterol
      dependent. The strongest decrease of monolayer ordering was observed for model
      raft system, while the excess of cholesterol present in the remaining mixtures
      was found to weaken the fluidizing effect of the drug.

PMID- 21862296
TI  - Mixed micelle formation with hydrophobic and hydrophilic Pluronic block
      copolymers: implications for controlled and targeted drug delivery.
AB  - Pluronic block copolymers offer affluent phase behavioral characteristics and are
      extensively investigated for drug delivery applications. Hydrophobic Pluronics
      produce larger aggregates whereas hydrophilic Pluronics often generate small
      sized micelles in aqueous milieu. To overcome the limitations and combine the
      advantages of different kinds of Pluronics the mixing of such two types of
      Pluronics is studied here, especially for hydrophobic Pluronic L81 and relatively
      hydrophilic Pluronic P123. Critical micelle concentration (CMC) of the developed
      binary mixtures was 0.032 mg/ml as evidenced from pyrene fluorescence
      spectroscopy and is located in between that of the individual Pluronics. Dynamic
      light scattering (DLS) showed very small particle sizes (~20 nm) and low
      polydispersity indices for most of the mixed micelles. Transmission electron
      microscopy (TEM) demonstrated spherical shape of micelles. Based upon the ratio
      of hydrophobic and hydrophilic Pluronics, dispersions of varied stability were
      obtained. With 0.1/1.0 wt.% and 0.5/3.0 wt.% of Pluronic L81/P123, stable
      dispersions were obtained. Stability was assessed from turbidity measurement,
      size analysis and clarity of dispersion on standing. Micelles were also found to
      be stable in bovine serum albumin (BSA) solution. Mixed micelles showed fairly
      high entrapment efficiency, loading capacity and sustained release profile for
      aceclofenac (Acl), a model hydrophobe. Presence of salt lowered Acl
      solubilization in micelles. Thermodynamic parameters for Acl solubilization in
      mixed micelles revealed high partition coefficient values and spontaneity of drug
      solubilization. Thus, the developed novel mixed micelles hold promise in
      controlled and targeted drug delivery owing to their very small size, high
      entrapment efficiency and stability.

PMID- 21862297
TI  - [Childhood obesity and sleep breathing disorders].
AB  - Obstructive sleep apnea (OSA) is common in childhood obesity and is mainly due to
      adenoid and tonsillar hypertrophy. Surgical management with adenotonsillectomy
      will be the first line of treatment for obese children with OSA in addition to
      weight loss. In addition, recent data suggested that sleep deprivation in infancy
      may be associated with obesity later in life, probably due to hypothalamic
      dysregulation with modifications in hormones involved in food intake regulation.
      It confirms that it is crucial to evaluate sleep for all obese children with
      questionnaire in order to improve their management and their quality of life.

PMID- 21862298
TI  - Acanthocorbis mongolica nov. spec.: description of the first freshwater loricate
      choanoflagellate (Acanthoecida) from a Mongolian lake.
AB  - A new acanthoecid choanoflagellate species, Acanthocorbis mongolica sp. nov. was
      found in preserved phytoplankton samples from the freshwater lake Bayan Nuur (Uvs
      Nuur Basin, NW Mongolia) in concentrations of up to 1.8*10(5)cellsL(-1). It is
      the first well-documented species of the mainly marine order Acanthoecida to be
      found in a freshwater lake. The lorica structures were studied with scanning
      electron microscopy. Key morphological features of the vase-shaped lorica are
      spine bases that are composed of multiple (2-4) parallel costal strips, and the
      existence of two transverse costae. The ecological implications of this find are
      discussed.

PMID- 21862299
TI  - [Alban Kohler (1874-1947): Inventor of grid therapy].
AB  - Grid (or sieve) therapy ("Gitter-" oder "Siebtherapie"), spatially fractionated
      kilo- and megavolt X-ray therapy, was invented in 1909 by Alban Kohler, a
      radiologist in Wiesbaden, Germany. He tested it on several patients before 1913
      using approximately 60-70kV Hittorf-Crookes tubes. Kohler pushed the X-ray tube's
      lead-shielded housing against a stiff grid of 1 mm-square iron wires woven 3.0
      3.5mm on center, taped tightly to the skin over a thin chamois. Numerous islets
      unshielded by iron in the pressure-blanched skin were irradiated with up to about
      6 erythema doses (ED). The skin was then thoroughly cleansed, disinfected, and
      bandaged; delayed punctate necrosis healed in several weeks. Although grid
      therapy was disparaged or ignored until the 1930s, it has been used successfully
      since then to shrink bulky malignancies. Also, advanced cancers in rats and mice
      have been mitigated or ablated using Kohler's concept since the early 1990s by
      unidirectional or stereotactic exposure to an array of nearly parallel
      microplanar (25-75MUm-wide) beams of very intense, moderately hard (median energy
      approximately 100 keV) synchrotron-generated X rays spaced 0.1-0.4mm on center.
      Such beams maintain sharp edges at high doses well beneath the skin yet confer
      little toxicity. They could palliate some otherwise intractable malignancies,
      perhaps in young children too, with tolerable sequelae. There are plans for such
      studies in larger animals.

PMID- 21862300
TI  - Nuclear medicine dosimetry: quantitative imaging and dose calculations.

PMID- 21862301
TI  - Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from
      ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic
      subjects: Results from a six month randomized controlled trial.
AB  - Recently, in a supplementation study over six months, it has been demonstrated
      that re-esterified omega-3 fatty acid triacylglycerols (n3-FA-rTAGs) led to a
      higher increase in omega-3-index compared to identical doses of n3-FA ethyl
      esters (n3-FA-EEs), suggesting a better long-term bioavailability. The aim of
      this study was to examine whether differences occur between the two forms in
      affecting fasting serum lipid levels. 150 dyslipidemic statin-treated
      participants were randomized to corn oil as a placebo or fish oil either as rTAG
      or EE in identical doses (1.01g EPA+0.67g DHA). No changes in total cholesterol,
      HDL or LDL levels were observed. In the rTAG-group, but not in the EE-group,
      fasting serum TAG levels were significantly reduced from baseline after three and
      six months. There was no significant difference between the two n3-FA-groups.
      However, serum TAG levels were significantly lowered after six months in the rTAG
      group compared to the placebo-group in contrast to the EE-group.

PMID- 21862302
TI  - Regulation of interleukin-10 and interleukin-22 expression in T helper cells.
AB  - Interleukin (IL)-10 and IL-22 are crucial regulators of inflammation during
      immune responses. While IL-10 functions to prevent excessive inflammation by
      acting on immune cells, IL-22 elicits innate responses from tissue epithelia and
      promotes wound healing. Although T helper (Th) cells are a major source for both
      cytokines, IL-10 and IL-22 are rarely co-expressed at high levels in the same
      cells. Here we discuss a number of common aspects as well as crucial differences
      in the molecular regulation of both cytokines that might explain their broad, but
      distinct expression among Th cell subsets.

PMID- 21862303
TI  - Allergic rhinitis and asthma: celebrating 100 years of immunotherapy.
AB  - Since Noon first described allergen immunotherapy a century ago the basic premise
      of subcutaneous injections (SCIT) of relevant aeroallergens to induce clinical
      tolerance has remained true [1]. Indeed, allergen immunotherapy did not change
      dramatically over the first 75 years, but over the past 25 years there have been
      a number of important advancements leading to newer approaches and novel
      formulations. Here we review the top 50 articles published in the past 2 years on
      allergens, environmental control, and immunotherapy for asthma and allergic
      rhinitis and the use of immunomodulators in allergic disease.

PMID- 21862304
TI  - The estimated pulmonary artery pressure can be elevated in Behcet's syndrome.
AB  - OBJECTIVES: To determine the frequency of elevated systolic pulmonary artery
      pressure (sPAP) estimated by echocardiography in Behcet's syndrome (BS) patients
      with pulmonary artery involvement (PAI), in healthy controls and in diseased
      controls with systemic sclerosis (SSc), as well as in BS patients without PAI.
      METHODS: We studied 3 groups of patients with BS (patients with PAI: n = 30, with
      vascular disease but without PAI: n = 26 and without vascular disease: n = 21),
      patients with SSc (n = 23) and healthy controls (n = 22). Systolic pulmonary
      artery pressure (sPAP) was estimated by echocardiography. The upper limit for a
      normal sPAP was arbitrarily set at 35 mmHg. We also evaluated cardiac function by
      echocardiography. Pulmonary function tests, a six-minute walking test (six-MWT)
      and several serum biomarkers were also studied. RESULTS: The frequency of
      patients with an elevated sPAP was significantly higher only among BS patients
      with PAI (17%) and among patients with SSc (26%). In addition, DL(CO) was
      decreased and pro-BNP levels were increased in BS patients with PAI, which are
      similar to the results in patients with SSc. Furthermore, BS patients with PAI
      also had mild RV diastolic dysfunction. CONCLUSIONS: When BS involves the
      pulmonary arteries, it can cause mild elevations in the estimated sPAP, decrease
      in DL(CO), mild cardiac dysfunction and increase in pro-BNP levels. These
      findings suggest that BS can also affect the small/micro vessels of the heart and
      the lungs in addition to the well-recognized large vessel disease.

PMID- 21862305
TI  - The practise and practice of Bourdieu: the application of social theory to youth
      alcohol research.
AB  - BACKGROUND: Some years ago Australian anthropologist David Moore criticised the
      predominant form of understanding youth alcohol consumption for residing with
      biomedical approaches that individualise and ultimately stigmatise drinking
      behaviour and 'ignore' the social context of consumption. Of interest here is the
      ongoing insufficient integration of alternative approaches to understanding young
      people's drinking. METHODS: This paper presents theoretically informed
      qualitative research that investigates why young Australian females (aged 14-17)
      drink and how social and cultural context form the basis, rather than the
      periphery, of their drinking experience. RESULTS: We demonstrate the utility of
      Pierre Bourdieu's sociological framework for delving beyond the dichotomy of
      young people's drinking decisions as either a determination of their cultural
      environment or the singular result of a rational individual's independent
      decision-making. The paper is presented in two parts. First, we provide the
      interpretation, or 'practise', of Bourdieu's concepts through an outline and
      application of his complex theoretical constructs. Specifically, the concept of
      symbolic capital (or social power) is applied. Second, our explication of
      Bourdieu's 'practice', or epistemological contributions, offers a
      methodologically grounded example to other researchers seeking to attain more
      complete understandings of the social processes underpinning youth alcohol
      consumption. CONCLUSION: A sociological approach to exploring the complex
      relationship between drinking and contextual social factors amongst young
      Australian females is an unchartered area of enquiry. We contribute new
      theoretically supported insights to create a more complete picture of young
      females' drinking behaviours.

PMID- 21862306
TI  - Recovery and distribution of incinerated aluminum packaging waste.
AB  - A study was performed into relations between physical properties of aluminum
      packaging waste and the corresponding aluminum scraps in bottom ash from three
      typical incineration processes. First, Dutch municipal solid waste incineration
      (MSWI) bottom ash was analyzed for the identifiable beverage can alloy scraps in
      the +2mm size ranges using chemical detection and X-ray fluorescence. Second,
      laboratory-scale pot furnace tests were conducted to investigate the relations
      between aluminum packaging in base household waste and the corresponding metal
      recovery rates. The representative packaging wastes include beverage cans, foil
      containers and thin foils. Third, small samples of aluminum packaging waste were
      incinerated in a high-temperature oven to determine leading factors influencing
      metal recovery rates. Packaging properties, combustion conditions, presence of
      magnesium and some specific contaminants commonly found in household waste were
      investigated independently in the high-temperature oven. In 2007, the bottom ash
      (+2mm fraction) from the AEB MSWI plant was estimated to be enriched by 0.1 wt.%
      of aluminum beverage cans scrap. Extrapolating from this number, the recovery
      potential of all eleven MSWI plants in the Netherlands is estimated at 720 ton of
      aluminum cans scrap. More than 85 wt.% of this estimate would end up in +6mm size
      fractions and were amenable for efficient recycling. The pot furnace tests showed
      that the average recovery rate of metallic aluminum typically decreases from
      beverage cans (93 wt.%) to foil containers (85 wt.%) to thin foils (77 wt.%). The
      oven tests showed that in order of decreasing impact the main factors promoting
      metallic aluminum losses are the packaging type, combustion temperature,
      residence time and salt contamination. To a lesser degree magnesium as alloying
      element, smaller packaging size and basic contaminations may also promote losses.

PMID- 21862307
TI  - Evaluation of different micro/nanobeads used as amplifiers in QCM immunosensor
      for more sensitive detection of E. coli O157:H7.
AB  - Micro/nanobeads with different materials (magnetic, silica and polymer) and
      different sizes (diameters from 30nm to 970nm) were investigated for their use as
      amplifiers in a quartz crystal microbalance (QCM) immunosensor for more sensitive
      detection of Escherichia coli O157:H7. The micro/nanobeads were conjugated with
      anti-E. coli antibodies. E. coli O157:H7 cells were first captured by the first
      antibody immobilized on the electrode surface, and then micro/nanobeads labeled
      secondary antibodies attached to the cells, and finally the complexes of antibody
      E. coli-antibody modified beads were formed. The results showed that antibody
      labeled beads lead to signal amplification in both the change in frequency
      (DeltaF) and the change in resistance (DeltaR). Since the penetration depth of
      the oscillation-induced shear-waves for a ~8MHz crystal is limited to 200nm, the
      interpretation of how the signal is amplified by the adsorbed particles was
      represented in terms of the coupled-oscillator theory. The amplification is not
      sensed in terms of increase in mass on the sensor surface. Amplification is
      sensed as a change in bacterial resonance frequency when the spheres adsorb to
      the bacteria. The change in the values of DeltaF caused by different
      micro/nanobeads (amplifiers) attaching on target bacterial cells is indicative of
      the ratio between the resonance frequency of the absorbed bacterial-particle
      complex (omega(s)), and the resonance frequency of the crystal (omega).

PMID- 21862308
TI  - Field-effect amperometric immuno-detection of protein biomarker.
AB  - The field-effect enzymatic detection technique has been applied to the
      amperometric immunoassay of the cancer biomarker, carcinoma antigen 125 (CA 125).
      The detection adopted a reagentless approach, in which the analyte, CA 125, was
      immobilized on the detecting electrode, which was modified using carbon
      nanotubes, and the detection signal was obtained by measuring the reduction peak
      current of the enzyme that was used to label the antibody. A gating voltage was
      applied to the detecting electrode, inducing increase in the signal current and
      therefore providing amplification of the detection signal. The voltage-controlled
      signal amplification of the detection system has increased the sensitivity and
      lowered the detection limit of the system. A detection limit of 0.9U/ml was
      obtained in the work.

PMID- 21862309
TI  - Chemical biotechnology in progress.

PMID- 21862311
TI  - Engineering of pathways, cells and tissues.

PMID- 21862310
TI  - Strategies for extended serum half-life of protein therapeutics.
AB  - With a growing number of protein therapeutics being developed, many of them
      exhibiting a short plasma half-life, half-life extension strategies find
      increasing attention by the biotech and pharmaceutical industry. Extension of the
      half-life can help to reduce the number of applications and to lower doses, thus
      are beneficial for therapeutic but also economic reasons. Here, a comprehensive
      overview of currently developed half-life extension strategies is provided
      including those aiming at increasing the hydrodynamic volume of a protein drug
      but also those implementing recycling processes mediated by the neonatal Fc
      receptor.

PMID- 21862312
TI  - Recent developments in engineering and delivery of protein and antibody
      therapeutics.

PMID- 21862313
TI  - Total dural irradiation: RapidArc versus static-field IMRT: a case study.
AB  - The purpose of this study was to compare conventional fixed-gantry angle
      intensity-modulated radiation therapy (IMRT) with RapidArc for total dural
      irradiation. We also hypothesize that target volume-individualized collimator
      angles may produce substantial normal tissue sparing when planning with RapidArc.
      Five-, 7-, and 9-field fixed-gantry angle sliding-window IMRT plans were
      generated for comparison with RapidArc plans. Optimization and normal tissue
      constraints were constant for all plans. All plans were normalized so that 95% of
      the planning target volume (PTV) received at least 100% of the dose. RapidArc was
      delivered using 350 degrees  clockwise and counterclockwise arcs. Conventional
      collimator angles of 45 degrees  and 315 degrees  were compared with 90 degrees 
      on both arcs. Dose prescription was 59.4 Gy in 33 fractions. PTV metrics used for
      comparison were coverage, V(107)%, D1%, conformality index (CI(95)%), and
      heterogeneity index (D(5)%-D(95)%). Brain dose, the main challenge of this case,
      was compared using D(1)%, Dmean, and V(5) Gy. Dose to optic chiasm, optic nerves,
      globes, and lenses was also compared. The use of unconventional collimator angles
      (90 degrees  on both arcs) substantially reduced dose to normal brain. All plans
      achieved acceptable target coverage. Homogeneity was similar for RapidArc and 9
      field IMRT plans. However, heterogeneity increased with decreasing number of IMRT
      fields, resulting in unacceptable hotspots within the brain. Conformality was
      marginally better with RapidArc relative to IMRT. Low dose to brain, as indicated
      by V5Gy, was comparable in all plans. Doses to organs at risk (OARs) showed no
      clinically meaningful differences. The number of monitor units was lower and
      delivery time was reduced with RapidArc. The case-individualized RapidArc plan
      compared favorably with the 9-field conventional IMRT plan. In view of lower
      monitor unit requirements and shorter delivery time, RapidArc was selected as the
      optimal solution. Individualized collimator angle solutions should be considered
      by RapidArc dosimetrists for OARs dose reduction. RapidArc should be considered
      as a treatment modality for tumors that extensively involve in the skull, dura,
      or scalp.

PMID- 21862314
TI  - Shedding light on the system: studying embryonic development with light sheet
      microscopy.
AB  - Light sheet-based fluorescence microscopy (LSFM) is emerging as a powerful
      imaging technique for the life sciences. LSFM provides an exceptionally high
      imaging speed, high signal-to-noise ratio, low level of photo-bleaching and good
      optical penetration depth. This unique combination of capabilities makes light
      sheet-based microscopes highly suitable for live imaging applications. There is
      an outstanding potential in applying this technology to the quantitative study of
      embryonic development. Here, we provide an overview of the different basic
      implementations of LSFM, review recent technical advances in the field and
      highlight applications in the context of embryonic development. We conclude with
      a discussion of promising future directions.

PMID- 21862315
TI  - Restricting self-renewal signals within the stem cell niche: multiple levels of
      control.
AB  - Germline stem cells (GSCs) were the first stem cells demonstrated to be regulated
      by the microenvironment or niche in the Drosophila ovary a decade ago. In the
      Drosophila ovary, as a stem cell divides, one daughter remaining in the niche
      continues to self-renew, and the other daughter positioned outside the niche
      undergoes differentiation. The niche produces bone morphogenetic proteins (BMPs)
      that only act within one cell diameter to ensure that at every division only one
      of two GSC daughters self-renews and thus maintains a stable GSC pool. Within the
      past decade, great progress has been made toward understanding how functions of
      BMP niche signals are restricted to GSCs. In this review, we have discussed
      multiple levels of control underlying the restriction of BMP signals within the
      niche. Because the niche mechanism has been shown to regulate stem cells in
      various organisms including mammals, the knowledge gained from the Drosophila GSC
      niche should help gain a better understanding of how niche signals are controlled
      in other stem cell systems.

PMID- 21862316
TI  - From Notch signaling to fine-grained patterning: Modeling meets experiments.
AB  - Notch signaling is the canonical signaling pathway between neighboring cells. It
      plays an important role in fine-grained patterning processes such as the
      formation of checkerboard-like differentiation patterns and sharp boundaries
      between developing tissues. While detailed information about many of the genes
      and proteins involved have been identified, we still lack a quantitative
      mechanistic understanding of these processes. Here we discuss several recent
      studies that provide novel insights into Notch-dependent patterning by combining
      mathematical models with quantitative experimental results. Such approaches allow
      identification of mechanisms and design principles controlling how patterns are
      generated in a reproducible and robust manner.

PMID- 21862317
TI  - What do expression dynamics tell us about the mechanism of transcription?
AB  - Single-cell microscopy studies have the potential to provide an unprecedented
      view of gene expression with exquisite spatial and temporal sensitivity. However,
      there is a challenge to connect the holistic cellular view with a reductionist
      biochemical view. In particular, experimental efforts to characterize the in vivo
      regulation of transcription have focused primarily on measurements of the
      dynamics of transcription factors and chromatin modifying factors. Such
      measurements have elucidated the transient nature of many nuclear interactions.
      In the past few years, experimental approaches have emerged that allow for
      interrogation of the output of transcription at the single-molecule, single-cell
      level. Here, I summarize the experimental results and models that aim to provide
      an integrated view of transcriptional regulation.

PMID- 21862319
TI  - Imaging and modeling growth and morphogenesis in plants.
AB  - The growth of tissues, organs or organisms derives from the coordinated
      activities of complex genetic regulatory networks. In addition to its molecular
      underpinnings, growth also generally involves significant changes in geometry. To
      fully understand morphogenesis in its molecular and physical contexts the
      development of an interdisciplinary approach is required associating biology,
      mathematics, and physics, which held together by computer science. Growth
      quantitation and digital simulations have been developed to generate and test the
      plausibilities of complex hypotheses. Increasingly, real-time live imaging
      protocols are becoming an essential part of this process. In this review, I
      discuss the evolution of imaging techniques in plant developmental biology and
      briefly examine the different ways in which these studies have shed light on
      growth and morphogenesis in plants.

PMID- 21862318
TI  - Pattern formation by receptor tyrosine kinases: analysis of the Gurken gradient
      in Drosophila oogenesis.
AB  - Spatial patterns of cell differentiation in developing tissues can be controlled
      by receptor tyrosine kinase (RTK) signaling gradients, which may form when
      locally secreted ligands activate uniformly expressed receptors. Graded
      activation of RTKs can span multiple cell diameters, giving rise to
      spatiotemporal patterns of signaling through the Extracellular Signal
      Regulated/Mitogen Activated Protein Kinase (ERK/MAPK), which connects receptor
      activation to multiple aspects of tissue morphogenesis. This general mechanism
      has been identified in numerous developmental contexts, from body axis
      specification in insects to patterning of the mammalian neocortex. We review
      recent quantitative studies of this mechanism in Drosophila oogenesis, an
      established genetic model of signaling through the Epidermal Growth Factor
      Receptor (EGFR), a highly conserved RTK.

PMID- 21862321
TI  - Effect of surfactants on PAH biodegradation by a bacterial consortium and on the
      dynamics of the bacterial community during the process.
AB  - The aim of this work was to evaluate the effect of a non-biodegradable (Tergitol
      NP-10) and a biodegradable (Tween-80) surfactant on growth, degradation rate and
      microbial dynamics of a polycyclic aromatic hydrocarbon (PAHs) degrading
      consortium (C2PL05) from a petroleum polluted soil, applying cultivable and non
      cultivable techniques. Growth and degradation rate were significantly lower with
      Tergitol NP-10 than that with Tween-80. Toxicity did not show any significant
      reduction with Tergitol NP-10 whereas with Tween-80 toxicity was almost depleted
      (30%) after 40 days. Regarding to the cultured bacteria, Pseudomonas and
      Stenotrophomonas groups were dominant during PAH degradation with Tergitol NP-10,
      whereas Enterobacter and Stenotrophomonas were dominant with Tween-80. DGGE
      analyses (PRIMER and MDS) showed that bacteria composition was more similar
      between treatments when PAHs were consumed than when PAHs concentration was still
      high. Community changes between treatments were a consequence of Pseudomonas sp.,
      Sphingomonas sp., Sphingobium sp. and Agromonas sp.

PMID- 21862320
TI  - Visualizing kinetochore architecture.
AB  - Kinetochores are large macromolecular assemblies that link chromosomes to spindle
      microtubules (MTs) during mitosis. Here we review recent advances in the study of
      core MT-binding kinetochore complexes using electron microcopy methods in vitro
      and nanometer-accuracy fluorescence microscopy in vivo. We synthesize these
      findings in novel three-dimensional models of both the budding yeast and
      vertebrate kinetochore in different stages of mitosis. There is a growing
      consensus that kinetochores are highly dynamic, supra-molecular machines that
      undergo dramatic structural rearrangements in response to MT capture and spindle
      forces during mitosis.

PMID- 21862322
TI  - Low-grade oils and fats: effect of several impurities on biodiesel production
      over sulfonic acid heterogeneous catalysts.
AB  - Different lipidic wastes and low-grade oils and fats have been characterized and
      evaluated as feedstocks for the acid-catalyzed production of FAME. The
      characterization of these materials has revealed significant contents of free
      fatty acids, Na, K, Ca, Mg, P, unsaponifiable matter and humidity. Arenesulfonic
      acid-functionalized SBA-15 silica catalyst has provided yields to FAME close to
      80% in the simultaneous esterification-transesterification of the different
      feedstocks, regardless of their nature and properties, using methanol under the
      following reaction conditions: 160  degrees C, 2 h, methanol to oil molar ratio
      of 30, 8 wt.% catalyst loading, and 2000 rpm stirring rate. Nevertheless,
      reutilization of the catalyst is compromised by high levels of impurities,
      especially because of deactivation by strong interaction of unsaponifiable matter
      with the catalytic sites. The conditioning of these materials by aqueous washing
      in the presence of cationic-exchange resin Amberlyst-15, followed by a drying
      step, resulted in a lower deactivation of the catalyst.

PMID- 21862323
TI  - Influence of step increases in hydraulic retention time on (RS)-MCPP degradation
      using an anaerobic membrane bioreactor.
AB  - The effects of different hydraulic retention time (HRT) on (RS)-MCPP utilisation
      was investigated by decreasing the feed flow rate in an anaerobic membrane
      bioreactor (AnMBR). Results showed an average COD removal efficiency of 91.4%,
      96.9% and 94.4% when the reactor was operated at HRT 3, 7 and 17 d, respectively.
      However, when the HRT was reduced to 1d, the COD removal efficiency declined to
      just only 60%, confirming the AnMBR is stable to a large transient hydraulic
      shock loads. The (RS)-MCPP removal efficiency fluctuated from 6% to 39% at HRT 3
      d, however when it was increased to 7 and 17 d, the removal efficiency increased
      to an average of 60% and 74.5%. In addition, (RS)-MCPP specific utilisation rates
      (SUR) were dependent on the HRT and gradually improved from 18 to 43 MUg mg VSS(
      1) d(-1) as flow rate increased.

PMID- 21862324
TI  - Flocculation performance of a cationic biopolymer derived from a cellulosic
      source in mild aqueous solution.
AB  - The flocculation behavior of cationic, quaternary ammonium groups containing
      cellulosic biopolymers, CDACs, synthesized by cationizing dialdehyde cellulose in
      mild aqueous solution was studied in a kaolin suspension. In particular, the role
      of CDAC dosage and solution pH, NaCl concentration, and temperature were
      clarified. In addition, the initial apparent charge densities (CDs), particle
      sizes, zeta-potential, and stability of CDs were determined. CDACs possessed a
      high flocculation activity in neutral and acidic solutions, but a significant
      decrease was observed in alkaline solutions (pH >9). This was also seen as a
      decline in the apparent CD and particle size of the CDACs in alkaline conditions.
      The measurements also indicated that the apparent CD decreased to a constant
      level of 3 mmol/g in aqueous solutions. However, no notable decrease in
      flocculation performance was obtained after several days of storage. Moreover,
      the variation of NaCl concentration and temperature did not affect the
      flocculation activity.

PMID- 21862325
TI  - Changes in the composition of an acid mine drainage microbial community upon
      successive transfers in medium containing low-grade copper sulfide.
AB  - A consortium of microorganisms from acid mine drainage samples was cultured in
      modified 9 K medium containing low-grade copper sulfide. The culture was
      maintained for sixty days and then transferred to fresh medium. This process was
      repeated three more times and a final consortium exhibiting a copper extraction
      rate of 89.3% was obtained. RFLP and microarrays analysis of 16S rRNA sequences
      retrieved from the consortia showed that Acidithiobacilluscaldus,
      Leptospirillumferriphilum, Sulfobacillus sp., Acidiphilium sp., and Sulfolobus
      spp. were represented in higher numbers in the consortia obtained in the copper
      containing medium than in the original consortium. In contrast, a decrease in
      Acidithiobacillus ferrooxidans, Alicyclobacillus sp., Pseudomonas sp., and
      Sulfobacillus thermosulfidooxidans was observed. The abundance of genes related
      to sulfur metabolism from At. caldus and Sulfolobus spp., iron oxidation from
      Leptospirillum sp. and metal resistance from most of the detected microorganisms
      increased as the consortium was successively transferred into fresh medium.

PMID- 21862326
TI  - Efficient lactobionic acid production from whey by Pseudomonas taetrolens under
      pH-shift conditions.
AB  - Lactobionic acid finds applications in the fields of pharmaceuticals, cosmetics
      and medicine. The production of lactobionic acid from whey by Pseudomonas
      taetrolens was studied in shake-flasks and in a bioreactor. Shake-flask
      experiments showed that lactobionic acid was a non-growth associated product. A
      two-stage pH-shift bioconversion strategy with a pH-uncontrolled above 6.5 during
      the growth phase and maintained at 6.5 during cumulative production was adopted
      in bioreactor batch cultures. An inoculation level of 30% promoted high cell
      culture densities that triggered lactobionic acid production at a rate of 1.12
      g/Lh. This methodology displayed efficient bioconversion with cheese whey as an
      inexpensive substrate for lactobionic acid production.

PMID- 21862327
TI  - Kinetic modelling of steam gasification of various woody biomass chars: influence
      of inorganic elements.
AB  - A study was performed on the influence of wood variability on char steam
      gasification kinetics. Isothermal experiments were carried out in a thermobalance
      in chemical regime on various wood chars produced under the same conditions. The
      samples exhibited large differences of average reaction rate. These differences
      were linked neither with the biomass species nor age and may be related to the
      biomass inorganic elements. A modelling approach was developed to give a
      quantitative insight to these observations. The grain model was used on one
      biomass of reference for temperatures between 750 and 900  degrees C and steam
      partial pressures between 0 and 0.27 bar. The model was applied to the other
      samples through the addition of an integral parameter specific to each sample. A
      satisfactory correlation was found between this parameter and the ratio
      potassium/silicium. This result highlighted the catalytic effect of potassium and
      inhibitor effect of silicium on the reaction.

PMID- 21862328
TI  - Identification and SAR of a new series of thieno[3,2-d]pyrimidines as Tpl2 kinase
      inhibitors.
AB  - We report here the synthesis and SAR of a new series of thieno[3,2-d]pyrimidines
      as potent Tpl2 kinase inhibitors. The proposed binding mode suggests the
      potential flipped binding mode depending on the substitution. Biacore studies
      show evidence of binding of these molecules to the protein kinase. The kinome
      inhibition profile of these molecules suggests good selectivity.

PMID- 21862329
TI  - Constructing transferrin receptor targeted drug delivery system by using
      doxorubicin hydrochloride and vanadocene dichloride.
AB  - Transferrin has shown potential in the delivery of anticancer drugs into
      primarily proliferating malignant cells that over-express transferrin receptors.
      Constructing transferrin receptor targeted drug delivery system has been
      widespread concerned. In this study, whether transferrin could transport
      noncovalent binding drugs into cancer cells has been investigated. Two
      representative compounds, doxorubicin hydrochloride (Dox) and vanadocene
      dichloride (Cp(2)VCl(2)), have been chosen to study the interactions with h-Tf
      and apo-Tf, and the influences in the presence of h-Tf and apo-Tf by using
      fluorescence spectroscopy, circular dichroism (CD) spectroscopy and MTT assay.
      The results have shown that both doxorubicin and Cp(2)VCl(2) could bind to h-Tf
      and apo-Tf but with different binding modes. The results of MTT assay demonstrate
      that the presence of both h-Tf and apo-Tf has enhanced the antiproliferative
      activity of Cp(2)VCl(2). However, the anticancer activity of the mixture of
      doxorubicin and h-Tf is basically the same as that of doxorubicin does. Our
      studies indicate that transferrin plays an important role in the transport and
      targeted delivery of Cp(2)VCl(2) into cancer cells.

PMID- 21862330
TI  - Double trouble: spinal muscular atrophy type II and seropositive myasthenia
      gravis in the same patient.
AB  - Autosomal recessive proximal spinal muscular atrophy is caused by deletions in
      the survival of motor neuron (SMN1) gene, while autoimmune myasthenia gravis is
      an acquired disorder. An association between these two diseases has not been
      reported. Our patient with intermediate spinal muscular atrophy (SMA type II) did
      not need alimentary or respiratory aid until age 51 when he suddenly developed
      bulbar weakness and respiratory insufficiency. Seropositive myasthenia gravis was
      confirmed and the corresponding symptoms resolved on treatment.

PMID- 21862331
TI  - Higher efficacy of letrozole in combination with trastuzumab compared to
      letrozole monotherapy as first-line treatment in patients with HER2-positive,
      hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA
      trial.
AB  - The eLEcTRA trial compared efficacy and safety of letrozole combined with
      trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR)
      positive metastatic breast cancer (MBC). Patients were randomized to either
      letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as
      first-line treatment. Additional 35 patients with HER2 negative and HR positive
      tumors received letrozole alone (arm C). Median time to progression in arm A was
      3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and
      15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39%
      for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01-8.84) and 77% in
      arm C (odds ratio 5.34, 95% CI 1.83-15.58). The eLEcTRA trial showed that the
      combination of letrozole and trastuzumab is a safe and effective treatment option
      for patients with HER2 positive and HR positive MBC.

PMID- 21862332
TI  - The impact of language on the expression and assessment of pain in children.
AB  - This paper focuses on the importance of language in the expression of pain.
      Variation in definitions of pain is presented, together with a review of the
      evidence examining the impact language may have on the way pain is expressed
      linguistically. The implications for conducting research with children who speak
      different languages are explored. Strategies such as using non-linguistic methods
      of communication, additional time required for conducting interviews and the
      inclusion of research team members from the same ethnic or linguistic background
      are presented.

PMID- 21862333
TI  - Does close proximity robot motion tracking alter gait?
AB  - Dynamic fluoroscopic imaging and three-dimensional model-image registration
      techniques provide detailed joint kinematic measurements for motions constrained
      to small volumes of space. Several groups are working to mount radiographic
      imaging hardware onto mobile platforms to provide these same imaging capabilities
      for observation of unrestricted activities. These dynamic radiographic imaging
      systems could provide accurate skeletal kinematics during a wide range of
      clinically relevant, daily activities. However, the premise that people move
      naturally when followed by a dynamic imaging system has not been evaluated. The
      goal of this study was to determine if a close-up robot tracking system affects
      natural free-speed gait. 14 healthy adults were recruited to walk through the
      workspace of a dynamic radiographic imaging system. Randomized walking trials
      were performed with and without the dynamic imaging system tracking the motions
      of the subject's left knee. With- and without-robot trials were compared using
      detailed temporal-spatial and frequency analysis of kinematic and kinetic
      parameters. On average, participants increase their stride length by 0.9 cm.
      There also were slight increases in unexplained variation in ankle
      flexion/extension and ground reaction forces compared to baseline measurements.
      The statistically significant differences indicate that, on average, people tried
      to move faster through the workspace of the dynamic radiographic imaging system
      while it was actively tracking their motion. These differences are small and
      potentially clinically irrelevant.

PMID- 21862334
TI  - Comparing the mid-vastus and medial parapatellar approaches in total knee
      arthroplasty: a meta-analysis of short term outcomes.
AB  - PURPOSE: Proponents of a mid-vastus (MV) approach for primary total knee
      arthroplasties (TKA) stress its importance in preserving function of the extensor
      mechanism with earlier rehabilitation and decreased prevalence of lateral
      release. We conducted a meta-analysis of randomised and quasi-randomised
      controlled trials to compare functional outcomes of the standard medial
      parapatellar (PP) and mid-vastus (MV) approaches in primary knee arthroplasties.
      METHODS: The study was conducted according to the guidelines described in the
      Cochrane Handbook for Systematic Reviews of Interventions. Methodological
      features were rated independently by two reviewers. RESULTS: We included 18
      studies involving 1040 patients with mean age of 69 (SD +/- 2.7) for the MV and
      68.8 (SD +/- 2.8) for the PP group. Using a MV approach led to significant
      improvement in flexion (mean difference (MD) 8.88, 95% confidence interval (CI)
      4.50 to 13.25, P<0.01) and visual analogue scale score (MD -1.72 95% CI -2.08 to 
      1.36, P<0.01) in the first week postoperatively and reduced the number of
      required lateral releases (risk difference -0.16 95% CI -0.30 to -0.01, P=0.03)
      with no increase in complication rates. CONCLUSION: We conclude that the MV
      approach may provide an alternative to the standard PP approach with earlier
      rehabilitation and decreased lateral release rates in primary TKA and no increase
      in complication rates.

PMID- 21862335
TI  - N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase
      inhibitors.
AB  - A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an
      efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine
      oxidase inhibitory activity for the first time. Structure-activity relationship
      analyses have been presented. Selected active xanthine oxidase inhibitors (3r,
      3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in
      potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the
      most potent xanthine oxidase inhibitor (IC(50)=2.45 MUM) as well as the most
      potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine
      oxidase by 3s was rationalized by its molecular docking into catalytic site of
      xanthine oxidase.

PMID- 21862336
TI  - Synthesis and glycosidase inhibitory profiles of functionalised morpholines and
      oxazepanes.
AB  - In this work libraries of morpholines and oxazepanes have been prepared via the
      reductive amination reaction between dialdehydes, derived from carbohydrates, and
      a range of amines. In this way, functionalised morpholines and oxazepanes have
      been prepared that include N-alkylated derivatives, disaccharide analogues, and
      ester containing derivatives. The abilities of these functionalised morpholines
      and oxazepanes to inhibit a broad panel of glycosidase enzymes, that are
      associated with a range of diseases, have been probed and in this way new
      inhibitors of a range of glycosidases, but particularly beta-d-galactosidase
      derived from Bovine kidney, have been discovered. N-Alkyl morpholines
      demonstrated the best inhibition profiles for this enzyme and derivatives (15a)
      (15d) acted as non-competitive inhibitors with IC(50) values of 55.1-88.6 MUM.
      Within this study, some preliminary structure-activity relationships are
      proposed, and it is demonstrated that N-substituted morpholines display better
      inhibitory profiles for the enzymes analysed than any of the N-substituted
      oxazepanes.

PMID- 21862337
TI  - Synthesis and biological evaluation of HQCAs with aryl or benzyl substituents on
      N-1 position as potential HIV-1 integrase inhibitors.
AB  - A series of new 5-hydroxylquinolone-3-carboxylic acids (HQCAs) with various aryl
      or benzyl substituents on N-1 position were synthesized and evaluated for their
      anti-HIV activity in C8166 cell culture. Most of the target compounds displayed
      activity against wide-type HIV-1 in the low micromolar range in infected C8166
      cells. The most active compound 5 g exhibited activity against wild-type HIV-1
      and HIV-1 mutant virus A17 with an EC(50) value of 3.17 and 17.88 MUM,
      respectively. The biological results and the docking study revealed that the
      substitution pattern on N-1 position of the quinolone core might contribute to
      physicochemical properties of HQCAs and resulted in great influence on their
      antiviral potency.

PMID- 21862338
TI  - Assessment of dopamine D1 receptor affinity and efficacy of three tetracyclic
      conformationally-restricted analogs of SKF38393.
AB  - To assess the effect of conformational mobility on receptor activity, the beta
      phenyl substituent of dopamine D(1) agonist ligands of the phenylbenzazepine
      class, (+/-)-6,6a,7,8,9,13b-hexahydro-5H-benzo[d]naphtho[2,1-b]azepine-11,12-diol
      (8), and its oxygen and sulfur bioisosteres 9 and 10, respectively, were
      synthesized as conformationally-restricted analogs of SKF38393, a dopamine D(1)
      selective partial agonist. Compounds trans-8b, 9, and 10 showed binding affinity
      comparable to that of SKF38393, but functionally, they displayed only very weak
      agonist activity. These results suggest that the conformationally-restricted
      structure of the analogs cannot adopt a binding orientation that is necessary for
      agonist activity.

PMID- 21862339
TI  - Imatinib-associated hyperpigmentation of the palate in post-HSCT patient.
AB  - Pigmentation of the oral mucosa can indicate a wide range of lesions or
      conditions. Some drugs are associated with pigmented lesions of oral cavity.
      Imatinib mesylate (Gleevec((r))) is a protein inhibitor used in the management of
      several hematological malignancies associated with dermatological side effects,
      like hyperpigmentation. We report the case of a 38-year-old male post-HSCT
      patient who had been using imatinib mesylate for over 5 years and presented with
      blue pigmentation on the hard palate, the left side of the nose and both ear
      lobes. The differential diagnosis of hyperpigmented lesions in the oral mucosa is
      also presented.

PMID- 21862340
TI  - Dislocation of the mandibular condyle into the middle cranial fossa causing an
      epidural haematoma.
AB  - Dislocation of the mandibular condyle into the middle cranial fossa is a rare
      complication of mandibular trauma due to anatomical and biomechanical factors.
      Owing to the proximity of the temporal glenoid fossa to the middle meningeal
      artery, there is the risk of serious sequelae in case of trauma. The authors
      report the case of a 36-year-old male patient, who was beaten up in a family
      dispute and presented with complex mandibular and maxillofacial fractures,
      including mandibular condyle intrusion into the middle cranial fossa causing
      extensive meningeal bleeding. The patient underwent immediate surgery, with
      evacuation of the epidural haematoma via a temporal approach. In addition open
      reduction and reconstruction of the temporal glenoid fossa via anatomic reduction
      of the fragments was performed. A functional occlusion was re-established via
      miniplate reconstruction of the complex mandibular body and ramus fractures.
      Prompt diagnosis and a multidisciplinary approach are essential to minimize the
      complications. Advanced imaging modalities of computed tomography are indicated.
      Treatment options should be individualized in particular in case of suspected
      neurological injury.

PMID- 21862341
TI  - UV-B induced alteration in purinergic receptors and signaling on HaCaT
      keratinocytes.
AB  - Although there are a number of recognized risk factors resulting in cutaneous
      malignancies, very little is known about the exact mechanism. In keratinocytes
      different purinergic receptors have been implicated to play essential roles in
      deciding the fate of the cells through regulating proliferation and
      differentiation. While P2Y receptors seem to control the former, P2X receptors,
      among which the P2X(7) receptor is associated with the induction of apoptosis,
      are likely to be responsible for the latter. Forty mJ/cm(2) UV-B irradiation
      decreased the number of viable cells as assessed using MTT assay. This
      irradiation decreased the amount of both P2X(1) and P2Y(2) receptors and
      essentially destroyed the P2X(7) receptors in surviving cells. Morphology of ATP
      induced Ca(2+) transients were altered in irradiated cells compared to control.
      The amplitude and the rate of rise of the transients were decreased and the
      return to resting [Ca(2+)](i) prolonged. This observation is consistent with the
      finding that in control cells mostly ionotropic, while in irradiated cells mostly
      metabotropic receptors were underlying the response to ATP. These alterations in
      the expression pattern of purinergic receptors and in the Ca(2+) transients could
      explain the observed decreased tendency for ATP-induced apoptosis and possibly
      contribute to the malignant transformation of keratinocytes.

PMID- 21862342
TI  - Basal and squamous cell carcinoma risks for golfers: an assessment of the
      influence of tee time for latitudes in the Northern and Southern hemispheres.
AB  - This study investigates the influence of tee time to determine the relative basal
      cell carcinoma (BCC) and squamous cell carcinoma (SCC) risk for weekly single
      round competition golfers located in the Northern and Southern latitude ranges
      between 25 degrees , 35 degrees , 45 degrees  and 55 degrees . A comparative risk
      methodology, employing annual erythemally effective ultraviolet (UVE) exposure
      calculations was used to determine BCC and SCC risk factors for golfers using a
      regular weekly tee time. Relative risk was found to be proportional to golf tee
      time with mid morning tee times generally presenting the greatest risk in each
      latitude range. The greatest contribution toward the risk of developing basal and
      squamous cell carcinoma was found to occur for golfers beginning weekly rounds
      mid to late morning, with specific risk factors of 1.47 (BCC) and 1.98 (SCC) in
      the Northern hemisphere compared with similar maximum risk factors of 1.51 (BCC)
      and 2.08 (SCC) in the Southern hemisphere occurring at comparable morning tee
      times. Differences in annual UVE exposure between the golfer and non-golfer were
      the largest determinant of BCC and SCC risk. Generally, these risks were found to
      decrease with lower latitude although contribution toward overall risk was
      influenced strongly by the global time zone of each studied golf course site.

PMID- 21862343
TI  - Hepatic FXR: key regulator of whole-body energy metabolism.
AB  - The farnesoid X receptor (FXR) is a nuclear receptor whose activation leads to
      alterations in pathways involved in energy metabolism. For example, it serves as
      a bile acid receptor in tissues such as the liver, and as an energy metabolism
      regulator in liver, muscle and adipose tissue. However, the effects of FXR
      activation are not exclusive to the tissue where it is present, because receptor
      crosstalk affects tissues throughout the body. It has been demonstrated that FXR
      regulates the metabolism of not just bile acids, but also of fats and hydrocarbon
      metabolites. FXR is currently under study as a therapeutic target for the
      treatment of diseases of excess, such as diabetes. Here we review the effects of
      FXR activation in the response of an organism to excess energy.

PMID- 21862344
TI  - Increased levels of cytokines and high-mobility group box 1 are associated with
      the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1
      influenza-infected children.
AB  - BACKGROUND: The 2009 A(H1N1) influenza virus has caused a large outbreak, and
      resulted in major complications of severe pneumonia and acute encephalopathy in
      the pediatric population in Japan. METHODS: This study examined six patients with
      acute encephalopathy, 34 patients with severe pneumonia, five patients with both
      pneumonia and encephalopathy, and 46 patients without severe complications. The
      concentrations of 27 cytokines were examined in the cerebrospinal fluid of
      patients with encephalopathy, and the levels of these cytokines, Cytochrome c,
      high-mobility group box 1 (HMGB1) were measured in the serum of all patients.
      RESULTS: Patients with severe pneumonia had higher serum concentrations of 16
      cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth
      factors, than patients with uncomplicated influenza. The distribution of 27
      cytokines in the CSF did not parallel the serum levels in 11 patients with acute
      encephalopathy. HMGB1 concentrations in the serum were significantly higher in
      pneumonia patients with or without encephalopathy than in uncomplicated influenza
      patients, and were significantly associated with the upregulation of 10
      cytokines. CONCLUSIONS: Elevated levels of Th2 cytokines appear to be unique to
      influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important
      role in the pathogenesis of severe pneumonia. There appear to be different
      pathologic processes for encephalopathy and pneumonia.

PMID- 21862346
TI  - Ultrasound-guided thoracic paravertebral catheter placement in a patient
      undergoing thoracotomy who had the relative contraindication of thrombocytopenia
      to epidural placement.

PMID- 21862347
TI  - Posterior glenohumeral joint dislocation: a rare complication of central venous
      cannulation in a patient undergoing coronary artery surgery.

PMID- 21862348
TI  - Cryoablation of atrial fibrillation in cardiac surgery: outcomes and myocardial
      injury biomarkers.
AB  - OBJECTIVE: Elevations of myocardial injury biomarkers after cardiac surgery
      without ablation of atrial fibrillation (AF) are related to perioperative
      myocardial ischemia and associated with an increased risk of mortality and
      cardiac events. However, there have not been any studies that examined the
      release of cardiac biomarkers after AF cryoablation procedures with concomitant
      cardiac surgery. The authors determined the levels of these biomarkers for 2
      different procedures involving cryoablation and assessed their clinical
      implications. DESIGN: A prospective cohort study with cardiac surgical patients.
      SETTING: A tertiary care university hospital. PARTICIPANTS: One hundred fifty-two
      cardiac surgical patients. INTERVENTIONS: Patients underwent 1 of 2 different
      cryoablation approaches: the modified Cox-Maze (CM) III procedure (n = 63) or the
      isolated left atrial (LA) maze procedure (n = 89). Plasma levels of cardiac
      biomarkers were measured at 1, 6, 12, and 24 hours after surgery. Twenty-four
      hour Holter monitoring was performed at 1 month and 1 year after surgery.
      MEASUREMENTS AND MAIN RESULTS: Both groups reached very high peak levels of CPK
      MB (CM group, 368 +/- 171.4 ng/mL and LA group, 203 +/- 86.4 ng/mL) and troponin
      T (CM, 8 +/- 4.5 ng/mL and LA, 3.4 +/- 2.4 ng/mL). The CPK, CPK-MB, and troponin
      T levels were significantly higher in the modified CM group compared with the LA
      maze group. In the first 24 hours after surgery, the average CPK-MB and troponin
      T values were 78.2 ng/mL higher and 2.3 ng/mL higher, respectively, in the CM
      group compared with the LA group. In both groups, 79% of the patients remained
      free of AF at 12 months after surgery. CONCLUSIONS: Cryoablation in cardiac
      surgery causes the release of very high levels of myocardial injury biomarkers.
      The modified CM lesion causes a greater elevation of serum biomarker levels than
      the isolated LA maze procedure, but this increase does not seem to have an
      adverse effect on rhythm or overall outcome. Cryoablation is a safe and effective
      surgical treatment for AF.

PMID- 21862349
TI  - Extracorporeal membrane oxygenation: a new way to study toxic drugs in chronic
      diseases.

PMID- 21862350
TI  - Interaction between dexmedetomidine and alpha-adrenergic receptors: emphasis on
      vascular actions.

PMID- 21862351
TI  - Exercise blood pressure response during assisted circulatory support: comparison
      of the total artificial [corrected] heart with a left ventricular assist device
      during rehabilitation.
AB  - BACKGROUND: The total artificial heart (TAH) consists of two implantable
      pneumatic pumps that replace the heart and operate at a fixed ejection rate and
      ejection pressure. We evaluated the blood pressure (BP) response to exercise and
      exercise performance in patients with a TAH compared to those with a with a
      continuous-flow left ventricular assist device (LVAD). METHODS: We conducted a
      single-center, retrospective study of 37 patients who received a TAH and 12
      patients implanted with an LVAD. We measured the BP response during exercise,
      exercise duration and change in tolerated exercise workload over an 8-week
      period. RESULTS: In patients with a TAH, baseline BP was 120/69 +/- 13/13,
      exercise BP was 118/72 +/- 15/10 and post-exercise BP was 120/72 +/- 14/12. Mean
      arterial BP did not change with exercise in patients with a TAH (88 +/- 10 vs 88
      +/- 11; p = 0.8), but increased in those with an LVAD (87 +/- 8 vs 95 +/- 13; p <
      0.001). Although the mean arterial BP (MAP) was negatively correlated with
      metabolic equivalents (METs) achieved during exercise, the association was not
      statistically significant (beta = -0.1, p = 0.4). MAP correlated positively with
      METs achieved in patients with LVADs (MAP: beta = 0.26, p = 0.04). Despite the
      abnormal response to exercise, patients with a TAH participated in physical
      therapy (median: 5 days; interquartile range [IQR] 4 to 7 days) and treadmill
      exercise (19 days; IQR: 13 to 35 days) early after device implantation, with
      increased exercise intensity and duration over time. CONCLUSIONS: During
      circulatory support with a TAH, the BP response to exercise was blunted. However,
      aerobic exercise training early after device implantation was found to be safe
      and feasible in a supervised setting.

PMID- 21862352
TI  - Sudden death and coronary intimal thickening.

PMID- 21862354
TI  - An atypical case of Lennox-Gastaut syndrome not associated with mental
      retardation: a nosological issue.
AB  - The characteristic electroclinical features of Lennox-Gastaut syndrome (LGS) have
      been extensively reported, but the influence of the constellation of slow spike
      and-wave (SSW) complexes with multiple seizure types (including atypical absence
      seizures [AAS] and tonic seizures [TS]) on patients with this syndrome is still
      unclear. We report the case of a 28-year-old woman who developed AAS and brief
      asymmetric TS at the age of 14 years. Her seizure disorder met diagnostic
      criteria for LGS (SSW on electroencephalogram and multiple seizure types), but
      there was no intellectual impairment and an interictal alpha EEG. Even 14 years
      after the onset of her epilepsy, she maintained fairly normal cognitive function,
      although she was bothered by frequent brief and subtle episodes of AAS and TS.

PMID- 21862356
TI  - Postoperative quality of life: development and validation of the "Dysfunction
      After Upper Gastrointestinal Surgery" scoring system.
AB  - BACKGROUND: Although postoperative quality of life is an important outcomes
      measure, few tools exist to evaluate patients specifically after upper
      gastrointestinal surgery. The previously developed Dysfunction After Upper
      Gastrointestinal Surgery (DAUGS)32 scoring system has been further refined to
      include just 20 items. This study was undertaken to validate the refined
      evaluation tool. STUDY DESIGN: The study was performed as a survey, administered
      to patients after upper gastrointestinal resection at 3 separate institutions.
      RESULTS: The DAUGS20 score after gastrectomy (n = 662) was 27.8 and that after
      esophagectomy (n = 221) was 36.1, showing a significant difference (p < 0.05).
      The score after distal gastrectomy (n = 282) was 25.4 and that after total
      gastrectomy (n = 149) was 32.0, showing a significant (p < 0.05) difference. The
      alpha coefficient of all items on the DAUGS20 system was 0.904 and Cronbach's
      alpha coefficients of the subscales were 0.612 to 0.856, demonstrating high
      reliability of this evaluation tool. In addition, 7 factors were extracted from
      the 20 items using definitive factor analysis, to verify validity. CONCLUSIONS:
      Patient quality of life should be evaluated as an outcomes measure after surgical
      resection for cancer, just as overall survival is analyzed. The DAUGS20 score is
      reliable, has validity in the evaluation of postoperative patients, and is a
      valuable tool to assess patient quality of life after upper gastrointestinal
      surgery for cancer.

PMID- 21862355
TI  - Overuse of CT in patients with complicated gallstone disease.
AB  - BACKGROUND: When compared with ultrasound, CT scans are more expensive, have
      substantial radiation exposure and lower sensitivity, specificity, positive, and
      negative predictive values for patients with gallstone disease. STUDY DESIGN: We
      reviewed data on patients emergently admitted with complicated gallstone disease
      between January 2005 and May 2010. Use of CT and ultrasound imaging on admission
      was described. Multivariate logistic regression was used to evaluate factors
      predicting receipt of CT. RESULTS: Five hundred and sixty-two consecutive
      patients presented emergently with complicated gallstone disease. Mean age was 45
      years. Seventy-two percent of patients were female, 46% were white, and 41% were
      Hispanic. Seventy-two percent of patients had an ultrasound during the initial
      evaluation and 41% had a CT. Both studies were performed in 25% of patients (n =
      141), 16% (n = 93) had CT only, and 47% (n = 259) had ultrasound only. CT was
      performed first in 67% of those who underwent both studies. Evening imaging (7 PM
      7 AM, odds ratio [OR] = 4.44; 95% CI, 2.88-6.85), increased age (OR = 1.14 per 5
      year increase; 95% CI, 1.07-1.21), leukocytosis (OR = 1.67; 95% CI, 1.10-2.53),
      and hyperamylasemia (OR = 2.02; 95% CI, 1.16-3.51) predicted use of CT.
      CONCLUSIONS: Our study demonstrates the overuse of CT in evaluation of
      complicated gallstone disease. Evening imaging was the biggest predictor of CT
      use, suggesting that CT is performed not to clarify the diagnosis, but rather a
      surrogate for the indicated study. Surgeons and emergency physicians should be
      trained to perform right upper quadrant ultrasound to avoid unnecessary studies
      in the appropriate clinical setting.

PMID- 21862357
TI  - Comments regarding 'total endovascular debranching of the aortic arch'.

PMID- 21862358
TI  - Noninvasive identification of peripheral vessels of oral and maxillofacial
      regions by using electrocardiography-triggered three-dimensional fast asymmetric
      spin-echo sequences.
AB  - OBJECTIVES: The aim of this study was to evaluate the 3-dimensional images of
      thinner main peripheral vessels in oral and maxillofacial regions made without
      contrast medium by using a new technique, fresh blood imaging (FBI). A second
      objective was to discern arteries from veins by using the combination of FBI with
      the subtraction technique. STUDY DESIGN: Images from FBI were compared with those
      from 3-dimensional phase-contrast magnetic resonance angiography (MRA) of blood
      vessels in 20 healthy subjects. All images were scored for visualization and
      image quality of the main blood vessels. In addition, appropriate flow-spoiled
      gradient pulses were applied to differentiate arteries from veins in the
      peripheral vasculature using a combination of FBI sequences and subtraction
      between systole- and diastole-triggered images. RESULTS: The scores of MRA using
      FBI for the visualization of thin blood vessels were significantly better than
      those using phase contrast, whereas scores for the visualization of main blood
      vessels were equal. Additionally, we succeeded in our initial attempt to
      differentiate arteries from veins with a reasonable acquisition time.
      CONCLUSIONS: Our initial experience shows that FBI could be a useful method to
      identify 3-dimensional vasculature and to differentiate arteries from veins among
      thinner peripheral vessels in the oral and maxillofacial regions without using
      contrast medium.

PMID- 21862361
TI  - Management and outcomes of three cases of rhinocerebral mucormycosis.
AB  - Mucormycosis is a rare opportunistic infection caused by fungi belonging to
      Mucorales order. The infection usually starts in the middle or inferior nasal
      meatus and then spreads to the paranasal sinuses and the orbit. Then it reaches
      the brain through the ethmoid and the orbit apex and can lead to lethargy,
      paralysis, and death. The majority of cases of rhinocerebral mucormycosis are
      diagnosed in patients with immunologic and metabolic disorders. Early diagnosis
      is fundamental, and so is medical therapy with amphotericin B along with surgical
      toilet of the compromised tissues. This article presents and discusses the
      management of 3 cases of rhinocerebral mucormycosis with different onsets,
      progressions, and outcomes.

PMID- 21862359
TI  - Microarray analyses of oral punch biopsies from acute myeloid leukemia (AML)
      patients treated with chemotherapy.
AB  - OBJECTIVE: Understanding the pathogenesis of chemotherapy-induced oral mucositis
      (CIOM) is vital to develop therapies for this common, dose-limiting side effect
      of cancer treatment. We investigated molecular events in CIOM from buccal mucosa
      tissue collected before and 2 days after chemotherapy from patients with acute
      myeloid leukemia (AML) and healthy controls by microarray analysis. METHODS:
      Microarray analysis was performed using Human Genome U133 Plus 2.0 Array on
      buccal mucosa punch biopsies from patients with AML before (n = 4) or after
      chemotherapy (n = 4), and from healthy controls (n = 3). Following Robust
      Multichip Average (RMA) normalization, we applied Linear Models for Microarray
      data (LIMMA) and Significance Analysis of Microarrays (SAM) for data analysis
      using the TM4/TMeV v4.5.1 program. RESULTS: LIMMA and SAM identified genes
      potentially affected by the presence of AML, including homeodomain-interacting
      protein kinase 1 (HIPK1), mex-3 homolog D (MEX3D), and genes potentially affected
      by chemotherapy, including argininosuccinate synthase 1 (ASS1), notch homolog 1
      (NOTCH1), zinc transporter ZIP6 (SLC39A6), and TP53-regulated inhibitor of
      apoptosis 1 (TRIAP1). The expression of 2 genes with potential biological
      significance in oral mucositis, ASS1 and SLC39A6 (alias LIV-1), was confirmed by
      quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR).
      CONCLUSIONS: Our results suggest that AML-specific deregulated immune responses
      and inflammatory tissue damage to the oral mucosa caused by chemotherapy may not
      be overcome by the natural cellular repair processes and therefore contribute to
      CIOM.

PMID- 21862363
TI  - Denture stomatitis treated with photodynamic therapy: five cases.
AB  - OBJECTIVE: Photodynamic therapy (PDT) is an effective method for Candida spp.
      inactivation in vitro and in vivo, but as yet, no clinical trial has been
      conducted. This report describes 5 cases of denture stomatitis (DS) treated with
      PDT. STUDY DESIGN: Five subjects with clinical and microbiologic diagnosis of DS
      were submitted to 6 sessions of PDT 3 times a week for 15 days. In each session,
      patients' dentures and palates were sprayed with 500 mg/L Photogem, and, after 30
      minutes of incubation, irradiated by light-emitting diode light source at 455 nm
      (37.5 and 122 J/cm(2), respectively). Cultures of Candida spp. from dentures and
      palates and standard photographs of the palates were taken at baseline (day 0),
      at the end of the treatment (day 15), and at follow-up time intervals (days 30
      and 60). RESULTS: Four patients showed clinical resolution of DS (no
      inflammation) after PDT sessions, and only 1 subject demonstrated reduction in
      palatal inflammation. Recurrence of DS was observed in 2 patients during the
      follow-up period. CONCLUSIONS: PDT appears to be an alternative treatment for DS.

PMID- 21862364
TI  - Quality assurance phantom for digital dental imaging.
AB  - OBJECTIVE: The purpose of this research was to develop a simple quality assurance
      phantom that could be used for the initial calibration and follow-up testing of
      commercially available intraoral digital imaging systems. STUDY DESIGN: A
      radiographic phantom was constructed that contains a calibrated step wedge for
      measuring dose response, an etched pattern of slits in a metallic background for
      measuring the spatial resolution in line pairs per millimeter, and 2 rows of
      wells of varying diameter and depth in an acrylic background for contrast-detail
      analysis. Quality assurance protocols were developed and validated. RESULTS: The
      quality assurance phantom provides a method of assessing a digital intraoral
      imaging system by measuring the sensitivity and dynamic range, the
      contrast/detail detectability and the spatial resolution. CONCLUSIONS: This
      quality assurance phantom can serve as an effective means to calibrate and
      monitor the performance characteristics of a digital dental intraoral imaging
      system.

PMID- 21862366
TI  - Mandibular traumatic peripheral osteoma: a case report.
AB  - An osteoma is a slow-growing, benign lesion comprising mature bone tissue.
      Osteomas rarely occur in maxillary bones, with the exception of the maxillary
      sinuses. Various possible etiologies have been proposed, including congenital
      anomalies, chronic inflammation, muscular activity, embryogenetic changes, and
      trauma. Here we present a case of an osteoma of the buccal plate of the mandible
      at the site where a sports-related traumatic injury occurred 15 years earlier.
      Both conventional and 3-dimensional x-ray examinations were used for diagnosis
      and preoperative evaluation of the possible involvement of the adjacent anatomic
      structures. The lesion was treated surgically without complications and the
      patient made a complete recovery. Histologic tests confirmed the preoperative
      diagnosis. A review of the international literature is also presented.

PMID- 21862367
TI  - Changes in diameter, cross-sectional area, and extent of canal-wall touching on
      using 3 instrumentation techniques in long-oval canals.
AB  - OBJECTIVE: The objective of this study was to compare the shaping ability of
      manual H-files, rotary nickel-titanium ProTaper system, and reciprocating
      SafeSiders in long oval-shaped root canals. STUDY DESIGN: The roots of 45 human
      premolars were sectioned at 2 levels in the middle third and reassembled using a
      3-piece metal mold. Pre- and postinstrumentation cross-sectional images were
      superimposed and evaluated in terms of change in buccolingual-to-mesiodistal
      canal ratio, maximum buccolingual and mesiodistal canal dimensions, and cross
      sectional areas. Ratios of touched canal wall and canal outline with more than
      200 MUm dentin removal to the original canal perimeter were also calculated.
      RESULTS: The buccolingual-to-mesiodistal ratio decreased after instrumentation
      with no difference among techniques (P > .05). The change in the buccolingual
      dimension was significantly less for SafeSiders compared with H-files and
      ProTaper (P < .05). The change in mesiodistal dimension was significantly less
      with SafeSiders compared with H-files only (P < .05). The change in area, in
      descending order, was as follows: H-files > ProTaper > SafeSiders (P < .05). The
      ratio of touched canal outline was highest with H-files, compared with ProTaper
      and SafeSiders (P < .05), and H-files recorded the highest ratio of canal outline
      with more than 200 MUm of dentin thickness removal (P < .05). CONCLUSIONS: None
      of the 3 instrumentation techniques completely prepared the oval root canal.
      Manual and rotary NiTi instrumentation may perform better than reciprocating
      SafeSider instrumentation in shaping oval canals.

PMID- 21862368
TI  - The use of zygomatic implants for the rehabilitation of atrophic maxillas with 2
      different techniques: Stella and Extrasinus.
AB  - The zygomatic implant anchorage is a surgical technique that provides a new
      perspective for patients with severe maxillary atrophy, increasing predictability
      and reduced cost of treatment, besides being a tool for the hardships of the
      rehabilitation of such a challenging region. This article describes 2 clinical
      cases with zygomatic implants with different techniques (Stella and Extrasinus)
      and both with immediate loading and accompanying clinical radiographic follow-up
      procedures of 12 and 24 months, respectively.

PMID- 21862370
TI  - Botulinum toxin treatment in upper limb spasticity: treatment consistency.
AB  - This study assessed treatment consistency of botulinum toxin administration in
      spastic upper limbs under pragmatic conditions, as derived through stability of
      dosages and between injections intervals. Over a period of 8 years, 153 children
      (81 with bilateral spastic cerebral palsy, 72 with unilateral) were treated
      according to accepted, experience-based guidelines with Botox and Dysport.
      Treatment response was based on assessment of spasticity and attainment of pre
      determined goals at 3, 6 and 12 months post each treatment. Mean age at treatment
      onset was 6y 4mo (SD: 4y 10mo), median F/U, 2.5 years (4 months-6 8/12 years).
      Number of injection sessions was 1-10; few had more than 6 sessions. In 106
      (69.28%) children, more than one anatomic regions of the limb were injected. Most
      (56.2%), had at least two injection sessions; median time interval between the
      sessions was 9 months (IQR: 4-35 months, similar for unilateral and bilateral
      cerebral palsy, p = 0.874). Children >4 years old at the first treatment had
      longer intervals between sessions (25.8%) compared to younger ones (p = 0.010).
      The mixed effects models demonstrated that botulinum toxin dosage was stable over
      subsequent visits (p = 0.144) and that intermediate intervals for subsequent
      visits were similar to the first one (p = 0.279).

PMID- 21862371
TI  - Visual expertise in paediatric neurology.
AB  - BACKGROUND: Visual expertise relies on perceptive as well as cognitive processes.
      At present, knowledge of these processes when diagnosing clinical cases mainly
      stems from studies with still pictures. In contrast, patient video cases
      constitute a dynamic diagnostic challenge that may simulate seeing and diagnosing
      a patient in person. AIMS: This study investigates visual attention and the
      concomitant cognitive processes of clinicians diagnosing authentic paediatric
      video cases. METHODS: A total of 43 clinicians with varying levels of expertise
      took part in this cross-sectional study. They diagnosed four brief video
      recordings of children: two with seizures and two with disorders imitating
      seizures. We used eye tracking to investigate time looking at relevant areas in
      the video cases and a concurrent think-aloud procedure to explore the associated
      clinical reasoning processes. RESULTS: More experienced clinicians were more
      accurate in visual diagnosis and spent more of their time looking at relevant
      areas. At the same time, they explored data less, yet they built and evaluated
      more diagnostic hypotheses. CONCLUSIONS: Clinicians of varying expertise analyse
      patient video cases differently. Clinical teachers should take these differences
      into account when optimising educational formats with patient video cases.

PMID- 21862373
TI  - [Reasons given by health profession students on whether or not they intend to be
      vaccinated against influenza when they are healthcare workers].

PMID- 21862372
TI  - High-pressure magic angle spinning nuclear magnetic resonance.
AB  - A high-pressure magic angle spinning (MAS) NMR capability, consisting of a
      reusable high-pressure MAS rotor, a high-pressure rotor loading/reaction chamber
      for in situ sealing and re-opening of the high-pressure MAS rotor, and a MAS
      probe with a localized RF coil for background signal suppression, is reported.
      The unusual technical challenges associated with development of a reusable high
      pressure MAS rotor are addressed in part by modifying standard ceramics for the
      rotor sleeve by abrading the internal surface at both ends of the cylinder. In
      this way, not only is the advantage of ceramic cylinders for withstanding very
      high-pressure utilized, but also plastic bushings can be glued tightly in place
      so that other removable plastic sealing mechanisms/components and O-rings can be
      mounted to create the desired high-pressure seal. Using this strategy, sealed
      internal pressures exceeding 150 bars have been achieved and sustained under
      ambient external pressure with minimal loss of pressure for 72 h. As an
      application example, in situ(13)C MAS NMR studies of mineral carbonation reaction
      intermediates and final products of forsterite (Mg(2)SiO(4)) reacted with
      supercritical CO(2) and H(2)O at 150 bar and 50 degrees C are reported, with
      relevance to geological sequestration of carbon dioxide.

PMID- 21862374
TI  - [Delineation of glioblastoma, simplicity to complexity, the contribution of
      imaging].
AB  - Delineation of glioblastoma is complex. Volumes conventionally defined: gross
      tumour volume (GTV) and clinical target volume (CTV) overlap and are separated
      according to imagery used. A review of these provides insight into the problem.
      If the correlations between imaging abnormalities and pathology seem to be
      relevant, the impact of their use in terms of local control and survival remains
      to be demonstrated.

PMID- 21862375
TI  - Spatial distribution of sonoluminescence and sonochemiluminescence generated by
      cavitation bubbles in 1.2 MHz focused ultrasound field.
AB  - An intensified charge coupled device (ICCD) camera was used to observe the
      spatial distribution of sonoluminescence (SL) and sonochemiluminescence (SCL)
      generated by cavitation bubbles in a 1.2 MHz focused ultrasound (FU) field in
      order to investigate the mechanisms of acoustic cavitation under different
      sonication conditions for FU therapeutic applications. It was found that SL
      emissions were located in the post-focal region. When the intensity of SL and SCL
      increased as the power rose, the growth of SCL was much higher than that of SL.
      In the post-focal region, the SCL emissions moved along specific paths and formed
      branch-like streamers. At the beginning of the ultrasound irradiation, cavitation
      bubbles generated SCL in both the pre-focal and the post-focal region. When the
      electrical power or the sonication time increased, the SCL in the post-focal
      region increased and became higher than that in the pre-focal region. The
      intensity of SCL in the focal region is usually the weakest because of
      "oversaturation". The spatial distribution of SCL near a tissue boundary differed
      from that obtained in free fields. It organized into special structures under
      different acoustic amplitudes. When the electrical power was relatively low, the
      SCL emission was conical shape which suggested a standing wave formation at the
      tissue-fluid boundary. When the electrical power exceeded a certain threshold,
      only a bright spot could be captured in the focus. The cavitation bubbles which
      centralized in the focus concentrated energy and hindered the formation of
      standing waves. With rising electrical power at high levels, besides a bright
      spot in the focus, there were some irregular light spots in pre-focal region,
      which indicated some cavitation bubbles or small bubble clusters achieved the
      threshold of SCL and induced the reaction with the luminol solution.

PMID- 21862376
TI  - Ultrasonication--a complementary 'green chemistry' tool to biocatalysis: a
      laboratory-scale study of lycopene extraction.
AB  - Lycopene is bequeathed with multiple bio-protective roles, primarily attributed
      to its unique molecular structure. The concomitant exploitation of two of the
      green chemistry tools viz., sonication and biocatalysis is reported here for the
      laboratory scale extraction of lycopene from tomato peel. The coupled system
      improved the extraction by 662%, 225% and 150% times over the unaided, only
      cellulase 'Onozuka R-10' treated and only sonication treated samples
      respectively. The sonication parameters (duration, cycle and amplitude) during
      the coupled operation were optimized using response surface methodology (RSM).
      Derivative UV-visible spectra (i.e., dA/dlambda and d(2)A/dlambda(2) against
      lambda), FTIR analysis, and DPPH scavenging test suggested that the reported
      extraction protocol did not affect the molecular structure and bioactivity of the
      extracted lycopene. The influence of sonication on the probable structural
      modulation (through UV-visible spectral analysis) and activity of the enzyme were
      also analyzed. A plausible mechanism is proposed for the enhanced extraction
      achieved via the coupled system.

PMID- 21862377
TI  - Effect of bandage thickness on interface pressure applied by compression
      bandages.
AB  - Medical compression bandages are widely used in the treatment of chronic venous
      disorder. In order to design effective compression bandages, researchers have
      attempted to describe the interface pressure applied by these bandages using
      mathematical models. This paper reports on the work carried out to derive the
      mathematical model used to describe the interface pressure applied by single
      layer bandage using two different approaches. The first assumes that the bandage
      thickness is negligible, whereas the second model includes the bandage thickness.
      The estimated pressures using the two formulae are then compared, simulated over
      a 3D representation of a real leg and validated experimentally. Both theoretical
      and experimental results have shown that taking bandage thickness into
      consideration while estimating the pressures applied by a medical compression
      bandage will result in more accurate estimation. However, the additional accuracy
      is clinically insignificant.

PMID- 21862378
TI  - A survey and comparative study on the instruments for glaucoma detection.
AB  - Glaucoma is one of the leading causes of irreversible blindness worldwide. It has
      been proposed that the intraocular pressure is a causative factor in the
      development of glaucoma, which is an optic neuropathy. This paper surveys the use
      of tonometers, gonioscopes, optical coherence tomographs, scanning laser
      polarimeters, scanning laser ophthalmoscopes (also known as scanning laser
      tomographs) and corneal pachymeters for the diagnosis and management of glaucoma.
      The working mechanisms as well as the comparative advantages and disadvantages of
      each of these instruments are presented.

PMID- 21862379
TI  - Spatial aberration vs. geographical substance: representing place in public
      health surveillance.
AB  - Public health surveillance involves the routine and ongoing collection, analysis
      and dissemination of health information for a variety of stakeholders-including
      both public health officials and the public. Much of the current focus of public
      health surveillance is on detecting aberrations in space-largely inspired by
      concerns about bioterrorism and newly emerging infectious diseases. We argue that
      the current focus on spatial aberrations has limited the development of public
      health surveillance by excluding a more explicit geographical understanding and
      representation of place. A more place-focused public health surveillance could
      represent geography in ways that are useful to a broader audience, provide
      information on the social and physical contexts related to health, facilitate a
      better understanding of health inequalities, and can benefit from local
      knowledge. Geographers can make important contributions to public health practice
      by contributing to more meaningful definitions of place in the design and
      operation of public health surveillance systems.

PMID- 21862380
TI  - Cytokine adjuvants for vaccine therapy of neoplastic and infectious disease.
AB  - Vaccination, the revolutionary prophylactic immunotherapy developed in the
      eighteenth century, has become the most successful and cost-effective of medical
      remedies available to modern society. Due to the remarkable accomplishments of
      the past century, the number of diseases and pathogens for which a traditional
      vaccine approach might reasonably be employed has dwindled to unprecedented
      levels. While this happy scenario bodes well for the future of public health,
      modern immunologists and vaccinologists face significant challenges if we are to
      address the scourge of recalcitrant pathogens like HIV and HCV and well as the
      significant obstacles to immunotherapy imposed by neoplastic self. Here, the
      authors review the clinical and preclinical literature to highlight the manner by
      which the host immune system can be successfully manipulated by cytokine
      adjuvants, thereby significantly enhancing the efficacy of a wide variety of
      vaccination platforms.

PMID- 21862381
TI  - Computational neuroimaging: localising Greek letters? Comment on Forstmann et al.

PMID- 21862382
TI  - Snf2-family proteins: chromatin remodellers for any occasion.
AB  - Chromatin facilitates the housing of eukaryotic DNA within the nucleus and
      restricts access to the underlying sequences. Thus, the regulation of chromatin
      structure provides an excellent platform for regulating processes that require
      information stored within genomic DNA. Snf2 proteins are a family of helicase
      like proteins that direct energy derived from ATP hydrolysis into the mechanical
      remodelling of chromatin structure. Here, we highlight some of the recent
      discoveries regarding this family of proteins and show Snf2 proteins have roles
      in many aspects of genetic metabolism. Recent developments include new insights
      into the mechanism for nucleosome spacing and histone dimer exchange; together
      with growing evidence for the involvement of Snf2 proteins in DNA repair.

PMID- 21862383
TI  - RNA helicases and remodeling proteins.
AB  - It is becoming increasingly clear that RNA molecules play a major role in all
      aspects of metabolism. The conformational state and stability of RNA are
      controlled by RNA remodeling proteins, which are ubiquitous motor proteins in the
      cell. Here, we review advances in our understanding of the structure and function
      of three major structural families of RNA remodeling proteins, the hexameric ring
      proteins, the processive monomeric RNA translocase/helicases, and the
      functionally diverse DEAD-box remodeling proteins. New studies have revealed
      molecular mechanisms for coupling between ATP hydrolysis and unwinding, the
      physical basis for regulatory control by cofactors, and novel functions for RNA
      remodeling proteins.

PMID- 21862384
TI  - Recent contributions from solid-state NMR to the understanding of membrane
      protein structure and function.
AB  - The plasma membrane functions as a semi-permeable barrier, defining the interior
      (or cytoplasm) of an individual cell. This highly dynamic and complex
      macromolecular assembly comprises predominantly lipids and proteins held together
      by entropic forces and provide the interface through which a cell interacts with
      its immediate environment. The extended sheet-like bilayer structure formed by
      the phospholipids is a highly adaptable platform whose structure and composition
      may be tuned to provide specialised functionality. Although a number of
      biophysical techniques including X-ray crystallography have been used to
      determine membrane protein structures, these methods are unable to replicate and
      accommodate the complexity and diversity of natural membranes. Solid state NMR
      (ssNMR) is a versatile method for structural biology and can be used to provide
      new insights into the structures of membrane components and their mutual
      interactions. The extensive variety of sample forms amenable for study by ssNMR,
      allows data to be collected from proteins in conditions that more faithfully
      resemble those of native environment, and therefore is much closer to a
      functional state.

PMID- 21862386
TI  - Force spectroscopy 101: how to design, perform, and analyze an AFM-based single
      molecule force spectroscopy experiment.
AB  - Single molecule force spectroscopy presents a deceptively simple approach to
      probing interaction between molecules and molecular assemblies on the nanoscale
      by measuring forces that it takes to pull the molecules apart. Yet, a more
      detailed analysis reveals a wealth of different behaviors and interesting
      physics. This article aims to explore basic physical concepts behind these
      experiments from a strictly practical point of using these data to extract
      meaningful information about the interactions. It also focuses on different
      loading regimes in these experiments, different kinetics that they cause, and
      different data interpretation that is required for measurements in those regimes.

PMID- 21862385
TI  - Inside the 40S ribosome assembly machinery.
AB  - Ribosome assembly involves rRNA transcription, modification, folding and cleavage
      from precursor transcripts, and association of ribosomal proteins (Rps). In
      bacteria, this complex process requires only a handful of proteins in addition to
      those needed for rRNA transcription, modification and cleavage, while in
      eukaryotes a large machinery comprising ~200 proteins in the yeast S. cerevisiae
      has been identified. Furthermore, while the bacterial assembly factors generally
      produce only cold-sensitive phenotypes upon deletion, most of the eukaryotic
      assembly factors are essential, comprising ~20% of essential yeast proteins. This
      review explores recent rapid progress in the structural and functional dissection
      of the 40S assembly machinery.

PMID- 21862387
TI  - Balancing eukaryotic replication asymmetry with replication fidelity.
AB  - Coordinated replication of eukaryotic nuclear genomes is asymmetric, with copying
      of a leading strand template preceding discontinuous copying of the lagging
      strand template. Replication is catalyzed by DNA polymerases alpha, delta and E,
      enzymes that are related yet differ in physical and biochemical properties,
      including fidelity. Recent studies suggest that Pol E is normally the primary
      leading strand replicase, whereas most synthesis by Pol delta occurs during
      lagging strand replication. New studies show that replication asymmetry can
      generate strand-specific genome instability resulting from biased deoxynucleotide
      pools and unrepaired ribonucleotides incorporated into DNA during replication,
      and that the eukaryotic replication machinery has evolved to most efficiently
      correct those replication errors that are made at the highest rates.

PMID- 21862388
TI  - Antitumor activity of cetuximab associated with the taxotere-cisplatin
      fluorouracil (TPF) combination on an orthotopic head and neck cancer model.
AB  - BACKGROUND: Cetuximab (Cet), an anti-epidermal growth factor receptor (EGFR)
      monoclonal antibody, is a standard of care in advanced head and neck (HN) cancer
      when combined with irradiation or cisplatin. The TPF association combining
      docetaxel (T), cisplatin (P) and fluorouracil (F) has become a chemotherapy of
      reference in the management of HN tumors. The aim of the study was to evaluate
      the anti-tumor activity of the association of Cet with TPF. In addition, the
      potential benefit from adding bevacizumab (Bev), an anti-VEGF monoclonal
      antibody, was examined. METHODS: Investigations were performed on CAL33 human
      head and neck cancer cell line (high content of EGFR) injected as an orthotopic
      xenograft into the mouth floor of nude mice. The anti-tumor efficacy of Cet (2.5
      mg/kg), Bev (20 mg/kg) and of TPF (at the MTD: T 20 mg/kg, P 6 mg/kg, F 17
      mg/kg), administered alone or in combination on day 3 and day 10 after tumor cell
      injection, was assessed on day 12 (animal sacrifice for ethical reasons, 10
      animals per treatment group). Tumor volume, tumor histology, tumor cell
      proliferation (Ki67, immunochemistry) and apoptosis (Bcl2, immunochemistry) were
      examined. RESULTS: As compared to controls, TPF-Cet and TPF-Cet-Bev had a
      significant impact on tumor volume and histological response. The highest
      efficacy was observed with the TPF-Cet combination. The effects of the TPF-Cet
      Bev association were not significantly different from those observed with TPF
      Cet. Data were corroborated by a diminution in Ki67 labeling and Bcl2 expression.
      CONCLUSION: The association of Cet with TPF can be considered a beneficial
      clinical option in advanced HN cancer patients.

PMID- 21862389
TI  - Cell-to-cell and long-distance siRNA movement in plants: mechanisms and
      biological implications.
AB  - In plants, once triggered within a single-cell type, transgene-mediated RNA
      silencing can move from cell-to-cell and over long distances through the
      vasculature to alter gene expression in tissues remote form the primary sites of
      its initiation. Although, transgenic approaches have been instrumental to
      genetically decipher the components and channels required for mobile silencing,
      the possible existence and biological significance of comparable endogenous
      mobile silencing pathways has remained an open question. Here, we summarize the
      results from recent studies that shed light on the molecular nature of the
      nucleic acids involved and on existing endogenous mechanisms that allow long
      distance gene regulation and epigenetic modifications. We further elaborate on
      these and other results to propose a unified view of various non-cell autonomous
      RNA silencing processes that appear to differ in their genetic requirement and
      modes of perpetuation in plants.

PMID- 21862390
TI  - Respiratory burst oxidases: the engines of ROS signaling.
AB  - Reactive oxygen species (ROS) play a key signal transduction role in cells. They
      are involved in the regulation of growth, development, responses to environmental
      stimuli and cell death. The level of ROS in cells is determined by interplay
      between ROS producing pathways and ROS scavenging mechanisms, part of the ROS
      gene network of plants. Recent studies identified respiratory burst oxidase
      homologues (RBOHs) as key signaling nodes in the ROS gene network of plants
      integrating a multitude of signal transduction pathways with ROS signaling. The
      ability of RBOHs to integrate calcium signaling and protein phosphorylation with
      ROS production, coupled with genetic studies demonstrating their involvement in
      many different biological processes in cells, places RBOHs at the center of the
      ROS network of cells and demonstrate their important function in plants.

PMID- 21862391
TI  - Is bacterial fatty acid synthesis a valid target for antibacterial drug
      discovery?
AB  - The emergence of resistance against most current drugs emphasizes the need to
      develop new approaches to control bacterial pathogens, particularly
      Staphylococcus aureus. Bacterial fatty acid synthesis is one such target that is
      being actively pursued by several research groups to develop anti-Staphylococcal
      agents. Recently, the wisdom of this approach has been challenged based on the
      ability of a Gram-positive bacterium to incorporate extracellular fatty acids and
      thus circumvent the inhibition of de novo fatty acid synthesis. The generality of
      this conclusion has been challenged, and there is enough diversity in the enzymes
      and regulation of fatty acid synthesis in bacteria to conclude that there is not
      a single organism that can be considered typical and representative of bacteria
      as a whole. We are left without a clear resolution to this ongoing debate and
      await new basic research to define the pathways for fatty acid uptake and that
      determine the biochemical and genetic mechanisms for the regulation of fatty acid
      synthesis in Gram-positive bacteria. These crucial experiments will determine
      whether diversity in the control of this important pathway accounts for the
      apparently different responses of Gram-positive bacteria to the inhibition of de
      novo fatty acid synthesis in presence of extracellular fatty acid supplements.

PMID- 21862393
TI  - FT-Raman, FT-IR spectra and total energy distribution of 3-pentyl-2,6
      diphenylpiperidin-4-one: DFT method.
AB  - FT-Raman and FT-IR spectra were recorded for 3-pentyl-2,6-diphenylpiperidin-4-one
      (PDPO) sample in solid state. The equilibrium geometries, harmonic vibrational
      frequencies, infrared and the Raman scattering intensities were computed using
      DFT/6-31G(d,p) level. Results obtained at this level of theory were used for a
      detailed interpretation of the infrared and Raman spectra, based on the total
      energy distribution (TED) of the normal modes. Molecular parameters such as bond
      lengths, bond angles and dihedral angles were calculated and compared with X-ray
      diffraction data. This comparison was good agreement. The intra-molecular charge
      transfer was calculated by means of natural bond orbital analysis (NBO).
      Hyperconjugative interaction energy was more during the pi-pi* transition. Energy
      gap of the molecule was found using HOMO and LUMO calculation, hence the less
      band gap, which seems to be more stable. Atomic charges of the carbon, nitrogen
      and oxygen were calculated using same level of calculation.

PMID- 21862392
TI  - New target for inhibition of bacterial RNA polymerase: 'switch region'.
AB  - A new drug target - the 'switch region' - has been identified within bacterial
      RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new
      target serves as the binding site for compounds that inhibit bacterial RNA
      synthesis and kill bacteria. Since the new target is present in most bacterial
      species, compounds that bind to the new target are active against a broad
      spectrum of bacterial species. Since the new target is different from targets of
      other antibacterial agents, compounds that bind to the new target are not cross
      resistant with other antibacterial agents. Four antibiotics that function through
      the new target have been identified: myxopyronin, corallopyronin, ripostatin, and
      lipiarmycin. This review summarizes the switch region, switch-region inhibitors,
      and implications for antibacterial drug discovery.

PMID- 21862394
TI  - Resonance light scattering method for the determination of DNA with cationic
      methacrylate based polymer nanoparticle probes.
AB  - Narrowly distributed cationic poly (methyl methacrylate-co-diacetone acrylamide)
      (P(MMA-DAAM)) nanoparticles were successfully prepared by microemulsion
      polymerization. Photon correlation spectrometer (PCS) measurement and
      transmission electron microscope (TEM) observation revealed that z-average
      particle size of P(MMA-DAAM) is ~27.5 nm. It was found that these cationic
      nanoparticles interact with DNA through electrostatic interaction to form P(MMA
      DAAM)-DNA complex, which significantly enhances the resonance light scattering
      (RLS) signal. Therefore, a novel method using this polymer nanoparticle as a new
      probe for the detection of DNA by RLS technique is developed in this paper. The
      results showed this method is very convenient, sensitive, and reproducible.

PMID- 21862395
TI  - Influence of alkaline earth metals on molecular structure of 3-nitrobenzoic acid
      in comparison with alkali metals effect.
AB  - The influence of beryllium, magnesium, calcium, strontium and barium cations on
      the electronic system of 3-nitrobenzoic acid was studied in comparison with
      studied earlier alkali metal ions. The vibrational FT-IR (in KBr and ATR
      techniques) and (1)H and (13)C NMR spectra were recorded for 3-nitrobenzoic acid
      and its salts. Characteristic shifts in IR and NMR spectra along 3-nitrobenzoates
      of divalent metal series Mg->Ba were compared with series of univalent metal Li
      >Cs salts. Good correlations between the wavenumbers of the vibrational bands in
      the IR spectra for 3-nitrobenzoates and ionic potential, electronegativity,
      inverse of atomic mass, atomic radius and ionization energy of metals were found
      for alkaline earth metals as well as for alkali metals. The density functional
      (DFT) hybrid method B3LYP with two basis sets: 6-311++G** and LANL2DZ were used
      to calculate optimized geometrical structures of studied compounds. The
      theoretical wavenumbers and intensities of IR spectra as well as chemical shifts
      in NMR spectra were obtained. Geometric aromaticity indices, atomic charges,
      dipole moments and energies were also calculated. The calculated parameters were
      compared to experimental characteristic of studied compounds.

PMID- 21862396
TI  - Sensitive competitive flow injection chemiluminescence immunoassay for IgG using
      gold nanoparticle as label.
AB  - A sensitive competitive flow injection chemiluminescence (CL-FIA) immunoassay for
      immunoglobulin G (IgG) was developed using gold nanoparticle as CL label. In the
      configuration, anti-IgG antibody was immobilized on a glass capillary column
      surface by 3-(aminopropyl)-triethoxysilane and glutaraldehyde to form
      immunoaffinity column. Analyte IgG and gold nanoparticle labeled IgG were passed
      through the immunoaffinity column mounted in a flow system and competed for the
      surface-confined anti-IgG antibody. CL emission was generated from the reaction
      between luminol and hydrogen peroxide in the presence of Au (III), generated from
      chemically oxidative dissolution of gold nanoparticle by an injection of 0.10 mol
      L(-1) HCl-0.10 mol L(-1) NaCl solution containing 0.10 mmol L(-1) Br(2). The
      concentration of analyte IgG was inversely related to the amount of bound gold
      nanoparticle labeled IgG and the CL intensity was linear with the concentration
      of analyte IgG from 1.0 ng mL(-1) to 40 ng mL(-1) with a detection limit of
      5.2*10(-10) gm L(-1). The whole assay time including the injections and washing
      steps was only 30 min for one sample, which was competitive with CL immunoassays
      based on a gold nanoparticle label and magnetic separation. This work
      demonstrates that the CL immunoassay incorporation of nanoparticle label and flow
      injection is promising for clinical assay with sensitivity and high-speed.

PMID- 21862397
TI  - Using Cognitive Work Analysis to fit decision support tools to nurse managers'
      work flow.
AB  - PURPOSE: To better understand the environmental constraints on nurse managers
      that impact their need for and use of decision support tools, we conducted a
      Cognitive Work Analysis (CWA). A complete CWA includes system analyses at five
      levels: work domain, decision-making procedures, decision-making strategies,
      social organization/collaboration, and worker skill level. Here we describe the
      results of the Work Domain Analysis (WDA) portion in detail then integrate the
      WDA with other portions of the CWA, reported previously, to generate a more
      complete picture of the nurse manager's work domain. METHODS: Data for the WDA
      were obtained from semi-structured interviews with nurse managers, division
      directors, CNOs, and other managers (n = 20) on 10 patient care units in three
      Arizona hospitals. The WDA described the nurse manager's environment in terms of
      the constraints it imposes on the nurse manager's ability to achieve targeted
      outcomes through organizational goals and priorities, functions, processes, as
      well as work objects and resources (e.g., people, equipment, technology, and
      data). Constraints were identified and summarized through qualitative thematic
      analysis. RESULTS: The results highlight the competing priorities, and external
      and internal constraints that today's nurse managers must satisfy as they try to
      improve quality and safety outcomes on their units. Nurse managers receive a
      great deal of data, much in electronic format. Although dashboards were perceived
      as helpful because they integrated some data elements, no decision support tools
      were available to help nurse managers with planning or answering "what if"
      questions. The results suggest both the need for additional decision support to
      manage the growing complexity of the environment, and the constraints the
      environment places on the design of that technology if it is to be effective.
      Limitations of the study include the small homogeneous sample and the reliance on
      interview data targeting safety and quality.

PMID- 21862398
TI  - A shared low-frequency oscillatory rhythm abnormality in resting and sensory
      gating in schizophrenia.
AB  - OBJECTIVES: We hypothesized that an oscillatory abnormality that is consistently
      observed across various testing paradigms may index an elementary neuronal
      abnormality marking schizophrenia risk. METHODS: Compared neural oscillations in
      resting EEG and sensory gating conditions in schizophrenia patients (n=128),
      their first-degree relatives (n=80), and controls (n=110) and calculated
      phenotypic and/or genetic correlation of the abnormal measure across these
      conditions. RESULTS: Using a uniform, single trial analytical approach, we
      identified two prominent oscillatory characteristics in schizophrenia: (1)
      augmented neural oscillatory power was pervasive in medicated schizophrenia
      patients in most frequencies, most prominent in the theta-alpha range (4-11 Hz)
      across the two paradigms (all p<0.007); and (2) their first-degree relatives
      shared significantly augmented oscillatory energy in theta-alpha frequency in
      resting (p=0.002) and insufficient suppression of theta-alpha in sensory gating
      (p=0.01) compared with normal controls. Heritability estimates for theta-alpha
      related measures for resting and gating conditions ranged from 0.44 to 0.49
      (p<0.03). The theta-alpha measures were correlated genetically with each other
      (RhoG=0.82+/-0.43; p<0.05). CONCLUSIONS: Augmented theta-alpha rhythm may be an
      elementary neurophysiological problem associated with genetic liability of
      schizophrenia. SIGNIFICANCE: This finding helps to refine key electrophysiologic
      biomarkers for genetic and clinical studies of schizophrenia.

PMID- 21862399
TI  - Carbamazepine reduces short-interval interhemispheric inhibition in healthy
      humans.
AB  - OBJECTIVE: We sought to elucidate the influence of centrally active drugs on
      interhemispheric inhibition (IHI) between primary motor cortices in healthy
      humans. METHODS: We therefore studied IHI before and 2h after intake of a single
      oral dose of carbamazepine, dextrometorphane, lorazepam, or placebo and compared
      it with the well known results for short-interval intracortical inhibition (SICI)
      and intracortical facilitation (ICF). Drugs were tested in separate sessions and
      in random order. RESULTS: While SICI and ICF were not altered by carbamazepine,
      IHI was reduced at the interstimulus interval of 8 ms. Dextrometorphane tended to
      enhance SICI and to reduce ICF and had no effect on IHI. Lorazepam reduced ICF as
      expected and enhanced IHI at the long intervals of 50 and 80ms. A moderate trend
      for interhemispheric facilitation was inconsistently observed at the interval 2
      ms and blocked by carbamazepine. In addition, carbamazepine increased the motor
      threshold. CONCLUSIONS: We conclude that circuits mediating short interstimulus
      intervals of IHI are susceptible to sodium channel blockade. SIGNIFICANCE: The
      results increase our knowledge of interhemispheric transmission.

PMID- 21862400
TI  - Comparison of Bifidobacterium breve strain Yakult transcriptomes in germ-free
      mice with those in fecal cultures.
AB  - Bifidobacteria are beneficial to human health, but the mechanism remains unknown.
      We employed oligonucleotide microarrays to identify the Bifidobacterium breve
      strain Yakult (BbrY) genes up-regulated specifically in mouse intestine. Based on
      BbrY transcriptional responses in germ-free mice and in fecal cultures, k-means
      clustering picked up 93 genes that were up-regulated in the mouse intestine and
      thereafter Venn analysis to exclude genes that were up-regulated in both the
      mouse intestine and the fecal culture classified 45 genes as up-regulated
      specifically in the mouse intestine. Most of those genes are involved in sugar
      transport or sugar liberation, although the functions of several genes are
      unknown. Most of these genes are clustered on the BbrY genome and appear to be
      organized into operons. Expressions of several genes were further investigated by
      real time PCR, revealing that their expression profiles were identical in the
      mouse cecum and colon. The up-regulation of genes involved in sugar
      liberalization and uptake suggests that BbrY could possibly maintain energy
      homeostasis inside the mouse intestine, which contains low quantities of readily
      fermentable sugars.

PMID- 21862401
TI  - Inconsistent sleep schedules and daytime behavioral difficulties in school-aged
      children.
AB  - OBJECTIVES: Current recommendations for healthy sleep in school-aged children are
      predominantly focused on optimal sleep duration (9-11h). However, given the
      importance of routine for circadian health, the stability of sleep/wake schedules
      may also be important, especially for daytime behavioral functioning. We examined
      the relationship between short sleep duration, sleep schedule instability and
      behavioral difficulties in a community sample of Australian children. METHODS:
      Children, aged 5-10 years (N=1622), without chronic health or psychological
      conditions, were recruited from primary schools in Adelaide, South Australia. A
      parent-report questionnaire was used to assess sleep/wake behavior. Behavioral
      functioning was assessed using the Strengths and Difficulties Questionnaire.
      RESULTS: Most children met sleep duration recommendations with approximately 5%
      reporting <9h and 3% >12h. Weekly variability of bed and rise times >1h were
      reported in up to 50% of children. Multinomial regression analysis revealed sleep
      duration <10h, bedtime latency >60 min, and bed and rise time variability >60 min
      significantly increased the risk of scoring in the 95th percentile for behavioral
      sub-scales. CONCLUSIONS: Inconsistent sleep schedules were common and, similar to
      short sleep duration, were associated with behavioral difficulties. Considering
      the lack of study in this area, further research is needed for the development of
      new recommendations, education and sleep health messages.

PMID- 21862402
TI  - Determinants of chlorination by-products in indoor swimming pools.
AB  - Water and air quality of fifteen swimming pools using chlorine disinfection was
      measured during eight sampling campaigns in Rennes, France. Concentrations of
      trihalomethanes (THMs) and trichloramine (NCl(3)) in air as well as
      concentrations of parameters, including total organic carbon (TOC), chlorine
      (free, combined and total), pH, Kjeldhal nitrogen (KN), chloride ions and THMs in
      water and air temperature, were measured. Water and air samples were collected
      during 3h in the morning and afternoon, during high and low attendance days, in
      summer and winter. Data analysis was perfomed by multivariate ordinary least
      square (OLS) and quantile (QR) regressions, from both data quality and other
      parameters such as the ratio between the number of visitors and the volume of
      water available V/W, the proportion of air re-circulated and the number of
      swimmers during sampling. The geometric means (GM+/-95% CIs) of the sum of THMs
      (TTHM) and NCl(3) in air were 74.9+/-6.7 MUg/m(3) and 190+/-10 MUg/m(3),
      respectively. As expected, concentrations of TTHM in air were correlated to
      concentrations of TTHM in water. Concentrations of TTHM and NCl(3) in air
      measured in winter were significantly higher than in summer, depicting that low
      air exchange rate in winter lead to accumulation of pollutants. NCl(3)
      (especially at higher quantiles) and TTHM concentrations in air were associated
      to the number of swimmers. NCl(3) was also linked to air temperature and pH.
      Moreover TTHM and NCl(3) in air seemed to be affected by additional determinants
      including the volume of hall and the ratio V/W. In a process of reducing
      exposure, the OLS regression provides useful information on key parameters
      influencing concentrations of THMs and NCl(3) in indoor swimming pools. In
      addition, QR allows identifying factors associated to elevated levels of
      contamination.

PMID- 21862403
TI  - Genotoxic hazard evaluation in welders occupationally exposed to extremely low
      frequency magnetic fields (ELF-MF).
AB  - Electric arc welding is known to involve considerable exposure to extremely low
      frequency magnetic fields (ELF-MF). A cytogenetic monitoring study was carried
      out in a group of welders to investigate the genotoxic risk of occupational
      exposure to ELF-MF. This study assessed individual occupational exposure to ELF
      MF using a personal magnetic-field dosimeter, and the cytogenetic effects were
      examined by comparing micronuclei (MN) and sister chromatid exchange (SCE)
      frequencies in the lymphocytes of the exposed workers with those of non-exposed
      control subjects (blood donors) matched for age and smoking habit. Cytogenetic
      analyses were carried out on 21 workers enrolled from two different welding
      companies in Central Italy and compared to 21 controls. Some differences between
      the groups were observed on analysis of SCE and MN, whereas replication indices
      in the exposed were found not to differ from the controls. In particular, the
      exposed group showed a significantly higher frequency of MN (group mean+/-SEM:
      6.10+/-0.39) compared to the control group (4.45+/-0.30). Moreover, the increase
      in MN is associated with a proportional increase in ELF-MF exposure levels with a
      dose-response relationship. A significant decrease in SCE frequency was observed
      in exposed subjects (3.73+/-0.21) compared to controls (4.89+/-0.12). The
      hypothesis of a correlation between genotoxic assays and ELF-MF exposure value
      was partially supported, especially as regards MN assay. Since these results are
      derived from a small-scale pilot study, a larger scale study should be
      undertaken.

PMID- 21862404
TI  - Injury prevention behaviour in community-level soccer players.
AB  - OBJECTIVE: To adapt and pilot test a method for undertaking routine surveillance
      of injury prevention behaviour in community-level soccer. DESIGN: Surveillance
      system using a cohort design. METHODS: Simple random samples were drawn from the
      player registration databases of two soccer federations. All players aged 13
      years or over who intended to play in a school or club competition during the
      2006 winter season were eligible. The cohort consisted of 687 male and 193 female
      players. The players were contacted each week and asked about their adherence to
      nationally recommended injury prevention measures. RESULTS: No more than 20% of
      players completed any form of pre-season screening. Almost all players warmed-up
      for player-matches (97%) and player-training sessions (93%). Eighty-one percent
      of players undertook some form of physical conditioning on at least one occasion
      in the off-season. Very few players (13%) reported receiving instruction on
      tackling technique pre-season. Shin-guards were worn in 99% of matches. For 61%
      of match injury events, the injured player continued to play after the injury
      occurred and in 65% of these cases, the player reported that in hindsight they
      should not have returned to play. CONCLUSIONS: The results provide a baseline
      measure of injury prevention behaviour in community-level soccer players. Future
      research, employing comparable surveillance methods, could be used to monitor
      progress on adherence to the injury prevention measures canvassed in this study.

PMID- 21862405
TI  - Off-pump coronary artery bypass grafting in elderly and high-risk patients--a
      review.
AB  - Elderly and high-risk patients are increasingly being considered for myocardial
      revascularisation. Most trials comparing the various options for
      revascularisation exclude elderly and 'high-risk' patients. We have reviewed the
      options for myocardial revascularisation for elderly patients, and for patients
      with a number of common 'high-risk' co-morbidities--diabetes mellitus, renal
      insufficiency, poor left ventricular ejection fraction, peripheral vascular
      disease, left main coronary artery disease and chronic obstructive pulmonary
      disease--with a focus on coronary artery bypass grafting without the use of
      cardiopulmonary bypass and aortic manipulation.

PMID- 21862406
TI  - PARP inhibitors in cancer: moving beyond BRCA.

PMID- 21862408
TI  - Resistance drives antibacterial drug development.
AB  - New resistance challenges continue to evolve and spread worldwide. In an
      otherwise mature field, antibacterial drug development is primarily driven by
      resistance trends with a focus on development of new analogs of known scaffolds
      to strengthen them against class-specific resistance mechanisms. Currently new
      analogs of cephalosporins (with or without beta-lactamase inhibitors),
      oxazolidinones, glycopeptides, quinolones, aminoglycosides, tetracyclines, and
      ketolides are in clinical studies. While showing some benefit, these new analogs
      only partially address the clinical crisis of multidrug-resistant pathogens; this
      is especially the case for Gram-negative bacteria. The medical community faces
      grim reality-general solutions to the treatment of rapidly spreading multidrug
      resistant bacteria are neither on the horizon nor anticipated.

PMID- 21862407
TI  - Olaparib in patients with recurrent high-grade serous or poorly differentiated
      ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open
      label, non-randomised study.
AB  - BACKGROUND: Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose)
      polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of
      this drug in patients without BRCA1 or BRCA2 mutations with advanced triple
      negative breast cancer or high-grade serous and/or undifferentiated ovarian
      cancer. METHODS: In this phase 2, multicentre, open-label, non-randomised study,
      women with advanced high-grade serous and/or undifferentiated ovarian carcinoma
      or triple-negative breast cancer were enrolled and received olaparib 400 mg twice
      a day. Patients were stratified according to whether they had a BRCA1 or BRCA2
      mutation or not. The primary endpoint was objective response rate by Response
      Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment
      were included in the analysis of toxic effects, and patients who had measurable
      lesions at baseline were included in the primary efficacy analysis. This trial is
      registered at ClinicalTrials.gov, number NCT00679783. FINDINGS: 91 patients were
      enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated
      between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64
      patients received treatment. 63 patients had target lesions and therefore were
      evaluable for objective response as per RECIST. In these patients, confirmed
      objective responses were seen in seven (41%; 95% CI 22-64) of 17 patients with
      BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46 without mutations. No
      confirmed objective responses were reported in patients with breast cancer. The
      most common adverse events were fatigue (45 [70%] of patients with ovarian
      cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]),
      vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven
      [27%]). INTERPRETATION: Our study suggests that olaparib is a promising treatment
      for women with ovarian cancer and further assessment of the drug in clinical
      trials is needed. FUNDING: AstraZeneca.

PMID- 21862409
TI  - Revisiting Beta-lactams - PK/PD improves dosing of old antibiotics.
AB  - Pre-clinical pharmacokinetic-pharmacodynamic assessments indicate Beta-lactam
      antibiotics have time-dependent killing, variable persistent antibiotic effects
      and that free drug T>MIC is the dominant pharmacodynamic index. Prolonged or
      continuous infusion therapy has improved microbiological responses in pathogens
      with MICs at or 2-4 fold higher than existing EUCAST clinical breakpoints in pre
      clinical studies. Human population pharmacokinetic modelling combined with Monte
      Carlo Simulation indicates improved pharmacodynamic target attainment rates and
      hence predicts improved clinical responses for those pathogens with raised MICs.
      However, the majority of human clinical trials comparing prolonged or continuous
      infusion to intermittent injection have failed to show superior clinical cures
      and for the most part microbiological successes. The exception being in various
      subgroup analyses. Future clinical trials need to focus on defining the T>MIC
      sizes associated with clinical or microbiological cure in man, on those subgroups
      of patients where continuous, or prolonged infusion, is likely to be of greatest
      benefit, seek to reduce pharmacokinetic variability by the use of therapeutic
      drug monitoring and include measurement of the risks of emergence of resistance
      in target pathogens At present, the clinical evidence base for prolonged or
      continuous infusion therapy is insufficiently strong to support widespread use.

PMID- 21862410
TI  - Towards nitric oxide based diagnostics: call to action.

PMID- 21862411
TI  - Iron disorders of genetic origin: a changing world.
AB  - Iron disorders of genetic origin are mainly composed of iron overload diseases,
      the most frequent being HFE-related hemochromatosis. Hepcidin deficiency
      underlies iron overload in HFE-hemochromatosis as well as in several other
      genetic iron excess disorders, such as hemojuvelin or hepcidin-related
      hemochromatosis and transferrin receptor 2-related hemochromatosis. Deficiency of
      ferroportin, the only known cellular protein iron exporter, produces iron
      overload in the typical form of ferroportin disease. By contrast, genetically
      enhanced hepcidin production, as observed in matriptase-2 deficiency, generates
      iron-refractory iron deficiency anemia. Diagnosis of these iron storage disorders
      is usually established noninvasively through combined biochemical, imaging and
      genetic approaches. Moreover, improved knowledge of the molecular mechanisms
      accounting for the variations of iron stores opens the way of novel therapeutic
      approaches aiming to restore normal iron homeostasis. In this review, we will
      summarize recent findings about these various genetic entities that have been
      identified owing to an exemplary interplay between clinicians and basic
      scientists.

PMID- 21862412
TI  - Membrane lipidomics for the discovery of new antiparasitic drug targets.
AB  - Advances in lipid separation methods and mass spectrometry technologies allow the
      fine characterization of the lipidome of parasites, ranging from unicellular
      protists to worms, which cause threatening infections in vertebrates, including
      humans. Specific lipid structures or lipid metabolic pathways can inspire the
      development of novel antiparasitic drugs. Changes in the lipid balance in
      membranes of parasites can also provide clues on the dynamics of drugs and some
      mechanisms of drug resistance. This review highlights recent trends in parasite
      lipidomics, combined with functional analyses, for the discovery of novel targets
      and the development of novel drugs.

PMID- 21862413
TI  - Babesiosis: an emerging infectious disease that can affect those who travel to
      the northeastern United States.
AB  - A case is presented of a healthy, 57 year-old male living in Ohio who traveled to
      Connecticut and later developed a severe case of babesiosis. The patient
      presented to his primary care physician with a history of intermittent fever and
      myalgias and was admitted to the hospital for investigation. On admission, he was
      found to have fever, left flank pain, and thrombocytopenia. The patient had an
      intact spleen, had no significant medical history, and had not received any blood
      products previously. During hospitalization, the patient developed pancytopenia
      and jaundice and became progressively more ill. A serendipitous conversation led
      to the investigation into babesiosis and empiric treatment. Infection with
      Babesia microti was confirmed by blood smear and PCR. In conclusion, obtaining a
      domestic, as well as international, travel history is important for identifying
      diseases, such as babesiosis, endemic to other areas.

PMID- 21862414
TI  - Benign rolandic epileptiform discharges are associated with mood and behavior
      problems.
AB  - Children with benign rolandic epilepsy (BRE) experience elevated rates of
      cognitive, behavioral, and affective problems. Frequent epileptiform spike
      discharges may impair behavioral functioning. To elucidate this relationship, we
      evaluated associations between the EEG spike frequency index (SI) and parental
      ratings of psychosocial adjustment and executive functioning in school-aged
      children with EEGs typical of BRE. Twenty-one children (6-12 years) participated.
      Parents completed validated questionnaires at a median of 5 months (range: 1-8)
      after a routine outpatient EEG. The EEG SI was calculated for wakefulness and
      sleep. The strength of association between the SI and behavioral variables was
      evaluated by simple and multivariate correlation. Higher awake and sleep SIs were
      associated with more symptoms of depression (P<0.001), aggression and conduct
      problems (P<0.01). Higher sleep SI was associated with executive dysfunction and
      anxiety (P<0.05). Symptoms of hyperactivity and inattention had no correlation.
      Increased epileptiform activity in children with BRE may predict higher rates of
      mood and behavioral problems.

PMID- 21862415
TI  - A phase II study of eribulin mesylate (E7389) in patients with advanced,
      previously treated non-small-cell lung cancer.
AB  - INTRODUCTION: This open-label phase II study assessed the efficacy and
      tolerability of eribulin, a non-taxane microtubule dynamics inhibitor with novel
      mechanism of action, as monotherapy in patients who have advanced non-small-cell
      lung cancer (NSCLC). PATIENTS AND METHODS: Enrolled patients had progressed
      during or after platinum-based doublet chemotherapy. Initially, two patient
      cohorts (taxane-pre-treated and taxane-naive) received eribulin mesylate (1.4
      mg/m(2)) as a 2- to 5-minute intravenous infusion on days 1, 8, and 15 of a 28
      day cycle. To assess tolerability of a second dosing schedule, a cohort of taxane
      pre-treated patients received eribulin on days 1 and 8 of a 21-day cycle. The
      primary endpoint was objective response rate (ORR) evaluated using Response
      Evaluation Criteria in Solid Tumors (RECIST) by independent radiographic review.
      RESULTS: One hundred three patients received eribulin. The ORR was 9.7% (all
      partial responses [PR]). Overall disease control rate (PR + stable disease) was
      55.3%. Median duration of response, progression-free survival, and overall
      survival were 5.8, 3.4, and 9.4 months, respectively. The most common drug
      related adverse events were neutropenia (54%; 49% grade 3/4); fatigue (49%; 11%
      grade 3, no grade 4); nausea (38%; 1% grade 3, no grade 4); alopecia (32%);
      anemia (29%, 4% grade 3/4) and neuropathy (23%; 2% grade 3, no grade 4). The 28
      day schedule was associated with many dose delays, interruptions, or omissions
      due to neutropenia (day 15). The 21-day cycle was well-tolerated. CONCLUSIONS:
      Eribulin monotherapy administered on days 1 and 8 of a 21-day cycle is active and
      tolerated as second- or later-line chemotherapy for NSCLC.

PMID- 21862416
TI  - Kyphoplasty and vertebroplasty: trends in use in ambulatory and inpatient
      settings.
AB  - BACKGROUND CONTEXT: Vertebral compression fractures (VCFs) are a substantial
      health concern. Kyphoplasty (KP) and vertebroplasty (VP) are vertebral
      augmentation procedures (VAPs) used to treat VCFs. PURPOSE: To compare VP and KP
      patient demographics and evaluate inpatient and outpatient utilization trends.
      STUDY DESIGN: Retrospective analysis of patient demographics, and inpatient and
      outpatient utilization trends, from California, New York, and Florida inpatient
      and ambulatory discharge databases. METHODS: Hospitalizations for VP and KP were
      identified from California, New York, and Florida inpatient and ambulatory
      discharge databases from 2005 to 2008. International Classification of Diseases,
      Ninth Revision diagnosis codes for pathologic, dorsal, and lumbar fracture of
      vertebrae were cross-referenced with ICD-9 procedure codes and Current Procedural
      Terminology codes to select the population. Patients younger than 40 years or
      those who underwent both procedures were excluded. RESULTS: The final population
      contained 61,851 VAPs (35,805 KPs and 26,046 VPs). Kyphoplasty showed increased
      inpatient and outpatient utilization. Vertebroplasty utilization remained at a
      low level of 6/100,000 capita. Kyphoplasty patients had more comorbidities than
      VP patients. In Florida in 2008, radiologists performed most VPs (52.3%) and
      orthopedists performed the most KPs (35.45%). Postoperative complication rates
      were significantly different; 0.79% of KPs had cardiac complications versus 0.57%
      of VPs (p=.0073). Respiratory complications occurred in 0.83% of KPs and 0.49% of
      VPs (p<.0001). CONCLUSIONS: Vertebral augmentation procedures have seen a
      continued increase in use from 2004 to 2008. Use of KP significantly outpaces the
      use of VP. Reasons for the increasing utilization of KP likely include financial
      incentives, the specialty performing KP, perceived safety, and effectiveness of
      vertebral height restoration. Conflicting evidence regarding which procedure is
      safer warrants further evaluation.

PMID- 21862417
TI  - Idiopathic spinal cord herniation at two separate zones of the thoracic spine:
      the first reported case and literature review.
AB  - BACKGROUND CONTEXT: Idiopathic spinal cord herniation (ISCH) is a rare cause of
      progressive myelopathy. Preoperative diagnosis can be made with magnetic
      resonance imaging (MRI). Many surgical techniques have been applied by various
      authors, and ISCH is usually reversible by surgical treatment. PURPOSE: To
      present a case of ISCH in two separate zones at two thoracic levels. To our
      knowledge, this is the first such case to be published in English literature. We
      also discuss the clinical findings, surgical procedures, and surgical outcomes
      for other previously reported cases of ISCH in the literature. STUDY DESIGN: Case
      report. METHODS: A 52-year-old woman with bilateral lower extremity weakness
      underwent thoracic MRI, which revealed transdural spinal cord herniation at two
      separate zones, namely, the T4-T5 and T5-T6 intervertebral disc levels. RESULTS:
      During surgery, the spinal cord was reduced, the two separate dural defects were
      connected, and the new single defect was restored then reinforced with a thin
      layer of fascial graft. The posterior dural defect was then closed with
      interrupted stitches. The patient's neurologic status was characterized by no
      changing of the preoperative motor status. Follow-up MRI scans showed that the
      cord was replaced in the dural sac and showed cord hyperintensity in the
      herniation levels. The patient could move with a cane at the sixth month
      postoperatively. CONCLUSIONS: Idiopathic spinal cord herniation is a rare
      clinical condition that should be considered in the differential diagnosis of
      paraplegia. Although progression of neurologic deficits can be very slow,
      reduction of the spinal cord and repair of the defect are crucial to stop or
      reverse the deterioration. The outcome for patients who initially have Brown
      Sequard syndrome is significantly better than for patients who presented with
      spastic paralysis. To our knowledge, this case study represents the first
      reported instance in which two separate anterior dural defects caused two levels
      of anterior spinal cord herniation.

PMID- 21862418
TI  - Inverse-planned gynecologic high-dose-rate interstitial brachytherapy: clinical
      outcomes and dose--volume histogram analysis.
AB  - PURPOSE: To present clinical outcomes and dose-volume histogram parameters of
      three-dimensional image-based high-dose-rate interstitial brachytherapy (HDR
      ISBT) in patients with primary or recurrent gynecologic cancer unsuitable for
      intracavitary brachytherapy (ICB). METHODS AND MATERIALS: Records of 43 women
      treated between 2001 and 2009 with iridium-192 gynecologic HDR-ISBT boost, using
      a Syed-Neblett template and inverse planning simulated annealing dose
      optimization, were reviewed. Median HDR-ISBT dose was 30Gy, delivered in 4
      6Gy/fraction. Dose-volume histogram parameters recommended by the Groupe Europeen
      de Curietherapie-European Society for Therapeutic Radiology and Oncology for
      image-based ICB were analyzed. Total doses were normalized to 2Gy fractions
      (biologically equivalent dose in 2Gy fractions). Local control (LC) and survival
      were calculated using Kaplan-Meier method. Toxicities were defined according to
      Common Terminology Criteria for Adverse Events v3.0. RESULTS: There were 34
      primary malignancies (cervix=12, vagina=15, Bartholin's gland=5, and vulva=2) and
      9 recurrences. International Federation of Gynecology and Obstetrics stage
      distribution for primary cancers was I=2, II=13, III=15, and IV=4. Median
      followup was 19.3 months (range, 0-92.2). Two-year LC was 87% for primary
      cancers, and 45% for recurrent cancers, respectively (p=0.0175). Median V(100),
      D(90), and D(100) for clinical target volume were 97.6%, 90.2, and 68.7Gy(10),
      respectively. Median bladder and rectal D(2)(cc) were 76.6 and 79.5Gy(3),
      respectively. Median urethral D(10) was 80.6Gy(3). Twelve patients experienced
      Grades 3 and 4 late morbidity, but toxicities were transient. Only 2 patients had
      persistent severe toxicities. A trend toward increased risk for vaginal necrosis
      was observed with a clinical target volume >84cc. CONCLUSIONS: HDR-ISBT may
      achieve good LC in gynecologic cancer unsuitable for ICB, especially in primary
      malignancies with a 2-year LC rate higher than 85%. Delivery of such high doses
      has potential advantages but may predispose to adverse effects, reversible in
      most cases.

PMID- 21862419
TI  - Characterization of upper thoracic spinal neurons receiving noxious cardiac
      and/or somatic inputs in diabetic rats.
AB  - The aim of the present study was to examine spinal processing of cardiac and
      somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was
      induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate
      buffer was injected in 14 control rats. After 4-11 weeks, the rats were
      anesthetized with pentobarbital, ventilated and paralyzed. A laminectomy enabled
      extracellular recording of T(3) spinal cord neuronal activity. Intrapericardial
      administration of a mixture of algogenic chemicals (bradykinin, serotonin,
      prostaglandin E(2) (all at 10(-5)M), and adenosine (10(-3)M)) was applied to
      activate nociceptors of cardiac afferent nerve endings. Furthermore, somatic
      receptive properties were examined by applying innocuous (brush and light
      pressure) and noxious (pinch) cutaneous mechanical stimuli. Diabetes-induced
      increases in spontaneous activity were observed in subsets of neurons exhibiting
      long-lasting excitatory responses to administration of the algogenic mixture.
      Algogenic chemicals altered activity of a larger proportion of neurons from
      diabetic animals (73/111) than control animals (55/115, P<0.05). Some subtypes of
      neurons exhibiting long-lasting excitatory responses, elicited prolonged duration
      and others, had a shortened latency. Some neurons exhibiting short-lasting
      excitatory responses in diabetic animals elicited a shorter latency and some a
      decreased excitatory change. The size of the somatic receptive field was
      increased for cardiosomatic neurons from diabetic animals. Cutaneous somatic
      mechanical stimulation caused spinal neurons to respond with a mixture of hyper-
      and hypoexcitability. In conclusion, diabetes induced changes in the spinal
      processing of cardiac input and these might contribute to cardiovascular
      autonomic neuropathy in patients with diabetes.

PMID- 21862421
TI  - Simultaneous quantification of VX and its toxic metabolite in blood and plasma
      samples and its application for in vivo and in vitro toxicological studies.
AB  - The present study was initiated to develop a sensitive and highly selective
      method for the simultaneous quantification of the nerve agent VX (O-ethyl S
      [2(diisopropylamino)ethyl] methylphosphonothioate) and its toxic metabolite (EA
      2192) in blood and plasma samples in vivo and in vitro. For the quantitative
      detection of VX and EA-2192 the resolution was realized on a HYPERCARB HPLC
      phase. A specific procedure was developed to isolate both toxic analytes from
      blood and plasma samples. The limit of detection was 0.1 pg/ml and the absolute
      recovery of the overall sample preparation procedure was 74% for VX and 69% for
      EA-2192. After intravenous and percutaneous administration of a supralethal doses
      of VX in anaesthetised swine both VX and EA-2192 could be quantified over 540 min
      following exposure. This study is the first to verify the in vivo formation of
      the toxic metabolite EA-2192 after poisoning with the nerve agent VX. Further
      toxicokinetic and therapeutic studies are required in order to determine the
      impact of EA-2192 on the treatment of acute VX poisoning.

PMID- 21862422
TI  - Novel analytical approach to a multi-sugar whole gut permeability assay.
AB  - Many pathophysiological conditions are associated with increased gastrointestinal
      permeability, reflecting an elevated risk of endotoxaemia, inflammation, and
      sepsis. Permeability tests are increasingly used in clinical practice to obtain
      information on gastrointestinal functioning, but tests are often restricted to
      the small intestine, and require large oral sugar doses. Therefore, a novel multi
      sugar assay was developed, allowing assessment of whole gut permeability changes
      in urinary and plasma samples collected at regular intervals from 10 healthy
      volunteers at baseline and after intake of monosaccharides (rhamnose and
      erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were
      analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection
      conditions were optimized. After centrifugation, chromatographic separation was
      achieved on an IOA-1000 column set at 30 degrees C. Column effluent was mixed
      with ammonia for sugar-ammonium adduct formation. The lower limit of detection
      was 0.05 MUmol/L for disaccharides and 0.1 MUmol/L for monosaccharides. Linearity
      for each probe was between 1 and 1000 MUmol/L (R(2): 0.9987-0.9999). Coefficients
      of variation were <5% in urine, and <9% in plasma. Recovery data were within the
      90% to 110% range at all spiked concentrations. This highly sensitive novel LC-MS
      approach resulted in a significant decrease of the detection limit for all sugar
      probes, allowing a 5-fold reduction of the commonly used lactulose dose and the
      addition of sugar probes to also assess the gastroduodenal and colon
      permeability. In combination with its extended application in plasma, these
      features make the novel assay a promising tool in the assessment of site-specific
      changes in gastrointestinal permeability in clinical practice.

PMID- 21862423
TI  - Comprehensive analysis of the intracellular metabolism of antiretroviral
      nucleosides and nucleotides using liquid chromatography-tandem mass spectrometry
      and method improvement by using ultra performance liquid chromatography.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are a key class of drugs for
      the treatment of HIV infection. NRTIs are intracellularly phosphorylated to their
      active triphosphate metabolites and compete with endogenous deoxynucleotides
      (dNTP) for substrate binding. It is therefore important to analyze the
      intracellular concentrations of these compounds to understand drug efficacy and
      toxicity. To that purpose an analytical platform was developed that is capable of
      analyzing 8 NRTIs, 12 phosphorylated NRTIs and 4 dNTPs in small numbers of
      peripheral blood mononuclear cells, i.e. 1 * 10(6) cells. The platform consists
      of two liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods: a
      reversed-phase method for NRTIs using positive electrospray ionization (ESI) and
      an ion-pair LC-MS/MS method for the phosphorylated compounds using negative ESI.
      The methods use the same LC-MS system and column and changing from one method to
      the other only includes changing the mobile phase. The methods were partially
      validated, focussing on sensitivity, accuracy and precision. Successful transfer
      of the methods to ultra performance liquid chromatography (UPLC) led to a
      significant improvement of speed for the analysis of NRTIs and sensitivity for
      both NRTIs and phosphorylated NRTIs. The latter was demonstrated by the improved
      separation by UHPLC of dGTP vs. AZT-TP and ATP which made direct analysis of dGTP
      possible using the optimal MS/MS transition thereby significantly improving the
      detection limit of dGTP. Typically LLOQs observed for both the NRTIs and
      phosphorylated NRTIs were 1 nM, while the mean accuracy varied between 82 and
      120% and inter- and intra-assay precision was generally <20%.

PMID- 21862424
TI  - The problem of energy transfer in proteins: physical modeling and biological
      reality: comment on "The theory of bio-energy transport in the protein molecules
      and its properties" by Pang Xiao-feng.

PMID- 21862425
TI  - A new health threat in Europe: Shiga toxin-producing Escherichia coli O104:H4
      infections.
AB  - Since early May 2011, a large outbreak of enterohemorrhagic gastroenteritis and
      hemolytic uremic syndrome (HUS) related to infections with Shiga toxin-producing
      Escherichia coli O104:H4 (STEC O104:H4) had been reported in Germany, which marks
      one of the largest outbreaks ever described of the HUS worldwide. The HUS
      outbreak was unusual, and there were important differences between this outbreak
      and previous large outbreaks, primarily those of STEC O157:H7 both clinically and
      microbiologically. This outbreak highlights the importance of collaboration of
      all aspects of public health to detect the outbreak, to identify and characterize
      the causative agent, to find the vehicles of transmission, and to control the
      infection.

PMID- 21862427
TI  - [Absolute lymphocyte count as a prognostic factor in children with acute
      lymphoblastic leukemia].
AB  - INTRODUCTION: Recent studies have suggested that the absolute lymphocyte count
      (ALC) may be a prognostic indicator in malignant diseases, in that those patients
      who have higher ALC at certain times during treatment may have a better chance of
      survival. The influence of T cells and natural killer cells in the immune system
      of the patient with cancer as a response to cancer cells is particularly noted.
      MATERIALS AND METHOD: We prospectively assessed the prognostic value of absolute
      lymphocytic count (ALC) in 105 pediatric patients with acute lymphoblastic
      leukemia (ALL), treated in the Cuban Immunology and Hematology Institute from
      1995 to 2008. ALC was studied at days 15 (ALC-15) and 28 (ALC-28) of treatment.
      RESULTS: In our patients, 1000 cells/uL was the median ALC value for patients who
      relapsed or died. Using 1000/uL we found that ALL patients with an ALC-15 <1000
      cells/MUl had a 5-year relapse free survival (RFS) of 51%. In contrast, an ALC-15
      >1000 cells/uL showed an excellent prognosis, with a 5-year RFS of 83% (p=0.02).
      Similarly in our study, an ALC-28 <1000 cells/MUl predicted a 5-year overall
      survival (OS) of 66%, whereas an ALC-28 >1000 cells/MUl predicted excellent
      outcome, with a 5-year OS of 86% (p=0.01). Importantly, ALC is also a strong
      predictor in multivariate analysis with known prognostic factors. ALC is a
      simple, statistically powerful measurement for patients with de novo ALL.
      CONCLUSIONS: The results, when combined with previous studies, demonstrate that
      ALC is a powerful new prognostic factor for a range of malignancies.

PMID- 21862426
TI  - [Socio-cultural, obstetric and anthropometric characteristics of newborn children
      of mothers who smoke in Spain].
AB  - INTRODUCTION: One in every four women smoke at the beginning of the pregnancy in
      Spain; of these, 25-50% give up smoking during gestation and most of them smoke
      again after childbirth. Maternal smoking has harmful effects on babies, such as
      low birth-weight with its resulting morbidity. The objective of this study is to
      compare the anthropometric and socio-cultural characteristics between newborns
      from smoking mothers and those from non- smoking ones. MATERIALS AND METHODS:
      Smoking habits and the socio-cultural characteristics were assessed from a sample
      of 1499 pregnant women, as well as their newborn anthropometric variables of
      their newborn babies during 2009 in the Aragon region of Spain. RESULTS: In the
      sample of 1499 pregnant women the prevalence of smoking during pregnancy was
      19.6%; among the Spanish women, 23% of them smoked during the gestation compared
      with only 11% in women from other countries. The smoker mothers were younger and
      they had a lower educational level than the non smoker ones; however, there were
      no statistical differences between their anthropometric characteristics. Newborns
      from smoker women in Aragon had a lower weigh at delivery (3155 vs. 3295 grams:
      p<.001) and a relative risk of low weight at birth for their gestational age of
      2.1 (95% CI: 1.35 - 2.97). The length and the rest of newborn anthropometric
      variables were also affected. CONCLUSION: The prevalence of smoking during
      gestation is high in Aragon. The mothers who smoke are younger and have different
      socio-cultural characteristics compared with non-smoker mothers. Maternal smoking
      habits have a harmful effect on newborn nutritional status, representing an
      avoidable risk of low weight at birth.

PMID- 21862428
TI  - Reply to: reconstruction of trochanteric pressure sores with pedicled
      anterolateral thigh myocutaneous flaps. J Plast Reconstr Aesthet Surg 2011
      May;64(5):671-6.

PMID- 21862429
TI  - Total resection of giant plexiform neurofibroma of the entire back in one stage
      by autologous tumor skin graft.

PMID- 21862430
TI  - European College of Orthodontics Commission on Membership and Tenure.

PMID- 21862432
TI  - Influence of surgical approach on functional outcome in reverse shoulder
      arthroplasty.
AB  - INTRODUCTION: Reverse shoulder arthroplasties (RSA) can be performed using a
      Deltopectoral (DP) or alternatively a Transdeltoid (TD) approach. HYPOTHESIS:
      Although the humeral cut is lower by TD approach, this should not affect
      postoperative functional results. MATERIAL AND METHODS: This retrospective
      multicentric study evaluated the complete medical records of RSA implanted
      between October 2003 and December 2008. Inclusion criteria were: follow-up of at
      least 1 year, a complete file including a comparative radiological work-up making
      it possible to analyze eventual arm and humeral lengthening. Evaluation of
      postoperative function was based on Active Anterior Elevation (AAE). RESULTS: We
      studied 144 RSA in 142 patients. One hundred and nine RSA were implanted by the
      DP approach and 35 by the TD approach. Mean lengthening of the humerus compared
      to the controlateral side by DP approach was 0.5+/-1.3 cm while there was a mean
      shortening of -0.5+/-1.0 cm by TD approach (P<0.001). The difference in cut was
      partially compensated by using thicker polyethylene inserts with the TD approach.
      Mean arm lengthening compared to the controlateral side was 1.7+/-1.7 cm by DP
      approach and 1.2+/-1.4 cm by TD approach (mean difference 0.5 cm; (95% CI -0.1;
      1.2). AAE for RSA by DP approach was 145+/-22 degrees  and 135+/-29 degrees  by
      TD approach (mean difference 10 degrees , 95% CI -1; 21). DISCUSSION: RSA results
      in improved AAE because of restored deltoid tension and an increase in the
      deltoid lever arm. The humeral cut by TD is lower, but this was partially
      corrected in this study by the use of thicker polyethylene inserts. Nevertheless
      there is no significant clinical difference in postoperative function between the
      two approaches.

PMID- 21862433
TI  - Vertebral body cage use in thoracolumbar fractures: outcomes in a prospective
      series of 23 cases at 2 years' follow-up.
AB  - INTRODUCTION: One objective of surgery in thoracolumbar spine fracture is to
      restore correct and lasting spinal statics. This may involve vertebral body
      replacement using an anterior approach. We here report results on a prospective
      series of 23 trauma patients managed by vertebral body replacement using an
      expandable cage. PATIENTS AND METHODS: The sex ratio was 2.28. Fifteen cases
      involved primary treatment of recent fracture and eight secondary surgery for non
      union or malunion. In 12 cases, posterior osteosynthesis was associated. Six
      patients were operated on using a classical approach and 17 using a video
      assisted minimally invasive approach. Pre- and perioperative data were recorded,
      with clinical scores (VAS and Oswestry) at 6 weeks, 3 months, 6 months, 1 year
      and 2 years. Radiologic follow-up assessed regional traumatic kyphosis (RTK),
      enabling calculation of regional traumatic angulation (RTA), with control CT to
      check fusion. RESULTS: Minimum follow-up was 2 years. There were no cases of
      postoperative neurological deterioration. There were three major postoperative
      complications: one hemothorax, one adhesive bowel occlusion, and one bilateral
      pneumothorax at 1 month. Mean Oswestry score at 6 months was 20%, and mean VAS
      score at 2 years was 0.36. Postoperative RTA showed a mean 7.34 degrees 
      improvement. Mean RTA reduction loss was 1.95 degrees  at 3 months, subsequently
      unchanged. All arthrodeses showed fusion at 6 months. CONCLUSION: Results were
      satisfactory with this technique, comparable to those reported in the literature.
      The development of minimally invasive approaches and improved instrumentation
      procedures optimize surgery and enhance anterior reconstruction tolerance.
      Lasting restoration of sagittal spinal curvature improves trauma patients'
      functional recovery.

PMID- 21862435
TI  - Pheochromocytoma and abdominal paraganglioma.
AB  - Pheochromocytomas (PHEO) and paragangliomas (PGL) are tumors derived from the
      sympathetic and parasympathetic nervous system. The parasympathetic-associated
      paragangliomas arising in the neck are usually non-functioning and are rarely
      encountered by general and visceral surgeons. The sympathetic-associated PHEO and
      PGL are usually functioning and most often arise in the abdomen. Because they
      harbor very specific characteristics (hypersecretion of catecholamines, familial
      origin in up to 30% of them, multiple locations, etc.) their perioperative
      management needs to be known by surgeons taking care of these patients in order
      to avoid operative disasters. Surgery can lead to perioperative hemodynamic
      modifications and sometimes catecholamine storm even in normotensive patients
      with PHEO and PGL. This emphasizes the need to exclude PHEO before any adrenal
      surgery as well as to medically prepare all patients with PHEO and PGL
      preoperatively. We review in this paper the pathophysiology and current
      perioperative management of patients with apparently sporadic PHEO and PGL.

PMID- 21862434
TI  - Acoustic neuroma risk in relation to mobile telephone use: results of the
      INTERPHONE international case-control study.
AB  - BACKGROUND: The rapid increase in mobile telephone use has generated concern
      about possible health risks of radiofrequency electromagnetic fields from these
      devices. METHODS: A case-control study of 1105 patients with newly diagnosed
      acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13
      countries using a common protocol. Past mobile phone use was assessed by personal
      interview. In the primary analysis, exposure time was censored at one year before
      the reference date (date of diagnosis for cases and date of diagnosis of the
      matched case for controls); analyses censoring exposure at five years before the
      reference date were also done to allow for a possible longer latent period.
      RESULTS: The odds ratio (OR) of acoustic neuroma with ever having been a regular
      mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for >=10
      years after first regular mobile phone use was 0.76 (0.52-1.11). There was no
      trend of increasing ORs with increasing cumulative call time or cumulative number
      of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of
      cumulative call time. In the 10th decile (>=1640 h) of cumulative call time, the
      OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use
      in those with >=1640 h of accumulated mobile phone use. With censoring at 5 years
      before the reference date the OR for >=10 years after first regular mobile phone
      use was 0.83 (0.58-1.19) and for >=1640 h of cumulative call time it was 2.79
      (1.51-5.16), but again with no trend in the lower nine deciles and with the
      lowest OR in the 9th decile. In general, ORs were not greater in subjects who
      reported usual phone use on the same side of the head as their tumour than in
      those who reported it on the opposite side, but it was greater in those in the
      10th decile of cumulative hours of use. CONCLUSIONS: There was no increase in
      risk of acoustic neuroma with ever regular use of a mobile phone or for users who
      began regular use 10 years or more before the reference date. Elevated odds
      ratios observed at the highest level of cumulative call time could be due to
      chance, reporting bias or a causal effect. As acoustic neuroma is usually a
      slowly growing tumour, the interval between introduction of mobile phones and
      occurrence of the tumour might have been too short to observe an effect, if there
      is one.

PMID- 21862436
TI  - Testis-isolated mantle cell lymphoma: a unique case.

PMID- 21862437
TI  - Approaches to the pathogenesis of primary biliary cirrhosis through animal
      models.
AB  - Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic liver
      disease of unknown etiopathogenesis that mainly affects middle-aged women.
      Patients show non-suppurative cholangitis with damage and destruction of the
      small- and medium-sized intrahepatic bile ducts. Characteristically, the disease
      is strongly associated with autoimmune phenomena such as the appearance of serum
      antimitochondrial autoantibodies (AMA) and portal infiltrating T cells against
      the inner lipoyl domain in the E2 component of the pyruvate dehydrogenase complex
      (PDC-E2). Here we review the major characteristics of a series of inducible and
      genetically modified animal models of PBC and analyze the similarities and
      differences to PBC features in humans.

PMID- 21862438
TI  - Brain volume changes in Parkinson's disease and their relationship with cognitive
      and behavioural abnormalities.
AB  - Cognitive and behavioral abnormalities are frequent in Parkinson's disease (PD)
      but their anatomical correlates are still uncertain. We assessed a cohort of 59
      PD patients with and without impulse control disorders (PD-ICDs and PD-CNTR) with
      magnetic resonance imaging and a comprehensive neuropsychological battery. Thirty
      five PD patients presented ICDs according to DSM-IV criteria and Minnesota
      Impulsive Disorders Interview. We found areas of significant brain atrophy in the
      middle and superior frontal gyrus in the whole cohort of 59 PD patients vs.
      healthy controls but there were no morphometric changes in PD-ICDs vs. PD-CNTR.
      This was consistent with cognitive findings of relatively preserved function in
      PD-ICDs with the exception for slower performance in the Trail Making Test B-A
      suggesting difficulties to maintain goal-directed tasks and suppress irrelevant
      responses. Voxel Based Morphometric regression analysis (VBM) carried out using
      TMTB-A as independent factor showed a negative gray matter correlation between
      high TMTB-A scores and left middle frontal cortex, right posterior cingulate
      area, anterior cingulate and supplementary motor area bilaterally. Our results
      suggest that PD is characterized by an overall loss of gray matter in pre-frontal
      regions. However, the contribution of these changes to the development of ICDs is
      marginal.

PMID- 21862439
TI  - Vitamin D in the healthy and inflamed central nervous system: access and
      function.
AB  - High exposure to vitamin D may protect against development and progression of
      multiple sclerosis (MS), possibly through the immunomodulatory properties of its
      biologically active metabolite 1,25-dihydroxyvitamin D. So far, most studies on
      the possible mechanisms for vitamin D involvement in MS have focused on immune
      modulation outside the central nervous system (CNS). However, vitamin D may also
      interfere with the pathophysiology of MS within the CNS. In this review, the
      potential presence and functions of vitamin D in the inflamed and healthy CNS are
      explored. We discuss that vitamin D, vitamin D binding protein (DBP), the vitamin
      D receptor (VDR) and enzymes needed for metabolism (CYP27B1) are present in the
      CNS. Both VDR and CYP27B1 are expressed on a variety of cells, including neurons,
      glial cells, and invading lymphocytes. Additionally, vitamin D has been
      postulated to play a modulating role in several key-processes in MS
      pathophysiology, including inflammation, demyelination, axonal damage, and
      remyelination. We conclude that a local role of vitamin D in the inflamed CNS is
      likely and potentially relevant to MS. Future studies should further characterize
      the impact of vitamin D on the local disease process of MS in the CNS.

PMID- 21862440
TI  - Toxicity and sorption kinetics of dissolved cadmium and chromium III on tropical
      freshwater phytoperiphyton in laboratory mesocosm experiments.
AB  - The objective of this study was to assess the interactive effects of Cd and Cr
      III on tropical phytoperiphyton community growth, metal sorption kinetics, as
      well as Cd and Cr mixtures toxicity to diatom assemblages in laboratory mesocosm
      experiments. A natural phytoperiphyton community sampled from the Monjolinho
      River (South of Brazil) was inoculated into seven experimental systems containing
      clean glass substrates for phytoperiphyton colonization. The communities were
      exposed to mixtures of dissolved Cd and Cr concentrations of 0.01 and 0.1mg.L(-1)
      Cd and 0.05 and 0.2mg.L(-1) Cr. Phytoperiphyton chlorophyll a, ash-free dry mass,
      growth rate, diatom cell density and diatom community composition were analyzed
      on samples collected after 1, 2 and 3 weeks of colonization. High Cd
      concentration (0.1mg.L(-1)) affects phytoperiphyton growth while high
      concentration of Cr (0.2mg.L(-1)) decreased the toxic effects of Cd on
      phytoperiphyton growth demonstrating the importance of studying metal mixtures in
      field studies. Shifts in species composition (development of more resistant
      species like Achnanthidium minutissimum (Kutzing) Czarnecki, and Nitzschia palea
      (Kutzing) Smith and reduction of sensitive ones like Fragilaria capucina
      Desmazieres, Navicula cryptocephala (Grunow) Cleve, Encyonema silesiacum
      (Bleisch) Mann, Eunotia bilunaris (Ehrenberg) Mills and Gomphonema parvulum
      (Kutzing) Kutzing), of phytoperiphyton communities with increasing Cd and Cr
      concentrations and exposure duration have been demonstrated in this study making
      phytoperiphyton communities appropriate monitors of metal mixtures in aquatic
      systems. Good Cd and Cr accumulation capacity by phytoperiphyton was demonstrated
      with total and intracellular metal content in phytoperiphyton reflecting the
      effects of dissolved concentrations of metal in the culture media and exposure
      duration. Increase in both Cd and Cr reduced sequestration of each other, with
      generally more Cd being sequestered compared to Cr. Field validation of the
      observed effects remains an interesting subject for further investigations.

PMID- 21862441
TI  - Increased plasma VEGF levels in major depressive or manic episodes in patients
      with mood disorders.
AB  - BACKGROUND: The neurotrophic hypothesis suggests that mood disorders are
      associated with dysfunction of neuronal networks under the influence of
      neurotrophic factors. Vascular endothelial growth factor (VEGF) is a neurotrophic
      factor as well as an angiogenic cytokine. METHODS: We examined plasma VEGF levels
      in 35 unipolar patients who were diagnosed with current major depressive disorder
      (MDD), 35 bipolar patients who were diagnosed with bipolar I disorder, manic
      episode (BM), and 60 healthy controls. The severity of depressive or manic
      symptoms was measured using the Hamilton Depression Rating Scale (HDRS) or the
      Young Mania rating scale (YMRS), respectively. RESULTS: Plasma VEGF levels were
      163.28+/-135.33 pg/mL in MDD patients, 199.82+/-182.59 pg/mL in BM patients, and
      110.05+/-109.57 pg/mL in healthy controls. Both MDD and BM patients had
      significantly higher VEGF levels than healthy controls when controlling for BMI
      as a covariate (p=0.010). Patients' VEGF levels were not correlated with either
      HDRS or YMRS scores. LIMITATIONS: We assessed plasma VEGF levels at one time
      point, and we did not determine the source of VEGF in our samples. CONCLUSIONS:
      Plasma VEGF levels were elevated in patients with acute episodes of major
      depressive disorder and bipolar disorder. Such an alteration of VEGF in acute
      episode, mood disorders may be associated with a neuroprotective role for VEGF.

PMID- 21862442
TI  - A marked deficiency in circulating and renal IGF-I peptide does not inhibit
      compensatory renal enlargement in uninephrectomized mice.
AB  - OBJECTIVE: Increase in kidney IGF-I levels due to its increased trapping from the
      circulation was hypothesized to be a key mediator of compensatory renal
      enlargement. We tested this hypothesis using genetically engineered mice with
      extremely low circulating IGF-I levels. DESIGN: Both IGF-I deficient (ID) and
      normal (N) mice underwent a uninephrectomy (UNx) and sacrificed 2 or 9days later.
      RESULTS: Initial body weight (BW) and kidney weight (KW) were significantly
      reduced in ID vs. N mice, while KW/BW ratios were similar. KW increased post-UNx
      to a comparable extent in ID and N mice (125+/-4 and 118+/-6% of pre-UNx KW,
      p<0.05 vs. C). Kidney IGF-I mRNA levels were similar in the ID and N mice and did
      not change post-UNx. Kidney IGF-I peptide levels pre-UNx were significantly lower
      in ID vs. N mice (25+/-5 vs. 305+/-39ng/g) and increased in both groups after
      UNx, remaining low in ID mice (45+/-4 in ID vs 561+/-64ng/g in N). IGF type 1
      receptor phosphorylation was unchanged. CONCLUSION: While a severe deficiency of
      circulating IGF-I impairs body growth, UNx induces a significant and proportional
      increase in renal mass in ID mice despite markedly decreased kidney IGF-I levels
      (>90% reduction) and no significant change in receptor phosphorylation. This all
      suggests that factors other than circulating and locally produced IGF-I are
      responsible for compensatory renal enlargement.

PMID- 21862443
TI  - Ursodeoxycholic acid in cystic fibrosis-associated liver disease.

PMID- 21862445
TI  - Role of the medial part of the intraparietal sulcus in implementing movement
      direction.
AB  - The contribution of the posterior parietal cortex (PPC) to visually guided
      movements has been originally inferred from observations made in patients
      suffering from optic ataxia. Subsequent electrophysiological studies in monkeys
      and functional imaging data in humans have corroborated the key role played by
      the PPC in sensorimotor transformations underlying goal-directed movements,
      although the exact contribution of this structure remains debated. Here, we used
      transcranial magnetic stimulation (TMS) to interfere transiently with the
      function of the left or right medial part of the intraparietal sulcus (mIPS) in
      healthy volunteers performing visually guided movements with the right hand. We
      found that a "virtual lesion" of either mIPS increased the scattering in initial
      movement direction (DIR), leading to longer trajectory and prolonged movement
      time, but only when TMS was delivered 100-160 ms before movement onset and for
      movements directed toward contralateral targets. Control experiments showed that
      deficits in DIR consequent to mIPS virtual lesions resulted from an inappropriate
      implementation of the motor command underlying the forthcoming movement and not
      from an inaccurate computation of the target localization. The present study
      indicates that mIPS plays a causal role in implementing specifically the
      direction vector of visually guided movements toward objects situated in the
      contralateral hemifield.

PMID- 21862444
TI  - Maternal cadmium exposure during pregnancy and size at birth: a prospective
      cohort study.
AB  - BACKGROUND: Cadmium (Cd) is an embryotoxic and teratogenic metal in a variety of
      animal species, but data from humans are limited. OBJECTIVES: The aim of the
      present study was to assess the effects of maternal Cd exposure in pregnancy on
      size at birth. METHODS: This prospective cohort study was nested in a population
      based nutritional supplementation trial in pregnancy conducted in rural
      Bangladesh. We selected women recruited from February 2002 through January 2003
      who had a singleton birth with measurements of size at birth and had donated a
      urine sample in early pregnancy for Cd analyses (n = 1,616). Urinary Cd was
      measured with inductively coupled plasma mass spectrometry and adjusted for
      specific gravity. RESULTS: Multiple linear regression analyses adjusted for sex
      and other potential confounders showed that maternal urinary Cd (median, 0.63
      MUg/L) was significantly negatively associated with birth weight [unstandardized
      regression coefficient B = -31.0; 95% confidence interval (CI): -59, -2.8] and
      head circumference (B = -0.15; 95% CI: -0.27, -0.026). However, associations
      appeared to be limited to girls, with little evidence of effects in boys. A 1
      MUg/L increase in Cd in maternal urine was associated with a 0.26-cm (95% CI: 
      0.43, -0.088 cm) and 0.24-cm (95% CI: -0.44, -0.030 cm) decrease in girls' head
      and chest circumferences, respectively, and a 45-g (95% CI: -82.5, 7.3 g)
      decrease in birth weight. Quantile regression analyses indicated that
      associations with maternal Cd were similar for girls of smaller (25th percentile)
      and larger (50th and 75th percentiles) sizes at birth. CONCLUSION: We found
      evidence of a sex difference in the association between maternal Cd exposure and
      birth size, which was apparent only in girls. Results add support for the need to
      reduce Cd pollution to improve public health.

PMID- 21862446
TI  - Orbitofrontal cortex and anterior cingulate cortex are modulated by motivated
      social cognition.
AB  - Neural research on social cognition has not examined motivations known to
      influence social cognition. One fundamental motivation in social cognition is
      positivity motivation, that is, the desire to view close others in an overly
      positive light. Positivity motivation does not extend to non-close others. The
      current functional magnetic resonance imaging study is the first to identify
      neural regions modulated by positivity motivation. Participants compared the
      personalities of a close other (i.e., romantic partner) and a non-close other
      (i.e., roommate) with their average peer. Romantic partners were perceived as
      above average under certain conditions; roommates were perceived as similar to an
      average peer across conditions. Neural regions previously associated with social
      cognition did not significantly relate to positivity motivation. Instead,
      orbitofrontal cortex (OFC) and, to a lesser extent, dorsal anterior cingulate
      cortex (ACC) activation increased when social targets were perceived as similar
      to an average peer. Furthermore, OFC activity negatively correlated with the
      extent to which a social target was perceived as above average. Intimacy with the
      social target modulated the extent to which ventral ACC distinguished positive
      from negative stimuli. The results expand current knowledge about neural regions
      associated with social cognition and provide initial information needed to create
      neural models of social cognition.

PMID- 21862447
TI  - Word intelligibility and age predict visual cortex activity during word
      listening.
AB  - The distractibility that older adults experience when listening to speech in
      challenging conditions has been attributed in part to reduced inhibition of
      irrelevant information within and across sensory systems. Whereas neuroimaging
      studies have shown that younger adults readily suppress visual cortex activation
      when listening to auditory stimuli, it is unclear the extent to which declining
      inhibition in older adults results in reduced suppression or compensatory
      engagement of other sensory cortices. The current functional magnetic resonance
      imaging study examined the effects of age and stimulus intelligibility in a word
      listening task. Across all participants, auditory cortex was engaged when
      listening to words. However, increasing age and declining word intelligibility
      had independent and spatially similar effects: both were associated with
      increasing engagement of visual cortex. Visual cortex activation was not
      explained by age-related differences in vascular reactivity but rather auditory
      and visual cortices were functionally connected across word listening conditions.
      The nature of this correlation changed with age: younger adults deactivated
      visual cortex when activating auditory cortex, middle-aged adults showed no
      relation, and older adults synchronously activated both cortices. These results
      suggest that age and stimulus integrity are additive modulators of crossmodal
      suppression and activation.

PMID- 21862449
TI  - Patient centredness and quality improvement efforts in hospitals: rationale,
      measurement, implementation.
AB  - QUALITY PROBLEM: Patient-centred care is increasingly being acknowledged as an
      integral part of evaluating health care. Yet, from a quality improvement
      perspective the rationale, measurement and implementation of strategies to
      improve patient-centred care is often subject to debate. OBJECTIVE: The aim of
      this paper is to review why quality improvement efforts should embrace patient
      centredness, to examine some of the measurement issues and to assess conceptual
      underpinnings that should inform both measurement and actions to improve patient
      centred care. LESSONS: The causal pathway through which quality improvement
      affects and/or is associated with patient centredness is complex and goes beyond
      patients' rights and assessing patient views. Interventions to improve patient
      centred care should reflect on key rationale, measurement strategy and underlying
      theory.

PMID- 21862448
TI  - Gene expression analysis of the embryonic subplate.
AB  - The subplate layer of the cerebral cortex is comprised of a heterogeneous
      population of cells and contains some of the earliest-generated neurons. In the
      embryonic brain, subplate cells contribute to the guidance and areal targeting of
      thalamocortical axons. At later developmental stages, they are predominantly
      involved in the maturation and plasticity of the cortical circuitry and the
      establishment of functional modules. We aimed to further characterize the
      embryonic murine subplate population by establishing a gene expression profile at
      embryonic day (E) 15.5 using laser capture microdissection and microarrays. The
      microarray identified over 300 transcripts with higher expression in the subplate
      compared with the cortical plate at this stage. Using quantitative reverse
      transcription-polymerase chain reaction, in situ hybridization (ISH), and
      immunohistochemistry (IHC), we have confirmed specific expression in the E15.5
      subplate for 13 selected genes, which have not been previously associated with
      this compartment (Abca8a, Cdh10, Cdh18, Csmd3, Gabra5, Kcnt2, Ogfrl1, Pls3,
      Rcan2, Sv2b, Slc8a2, Unc5c, and Zdhhc2). In the reeler mutant, the expression of
      the majority of these genes (9 of 13) was shifted in accordance with the altered
      position of subplate. These genes belong to several functional groups and likely
      contribute to synapse formation and axonal growth and guidance in subplate cells.

PMID- 21862450
TI  - Scrutinizing ciliopathies by unraveling ciliary interaction networks.
AB  - Research of cilia has gained significant momentum in the last 15 years, as an
      increasing number of human genetic diseases were found to be caused by disruption
      of a protein that localizes to cilia. These ciliopathies are as diverse as the
      functions of the associated proteins, covering a spectrum of overlapping
      phenotypes that ranges from relatively mild characteristics in isolated tissues
      with a late onset, to severe defects of multiple tissues with an onset early in
      embryogenesis that is incompatible with life. As cilia harbour many receptors and
      components of key signaling cascades, such as Hedgehog, Wnt, Notch and Hippo
      signaling, disruption of ciliary function has severe consequences. Recent
      (affinity) proteomics studies have focused on the composition and dynamics of
      ciliary protein interaction networks. This has unveiled important knowledge about
      the highly ordered, interconnected but very dynamic nature of the cilium as a
      molecular machine. Disruption of the members of the same functional modules of
      this machine leads to similar phenotypes, and detailed analyses of the binding
      repertoire, the biochemical properties and the biological functions of these
      modules have yielded new ciliopathy genes as well as new insights into the
      pathogenic mechanisms underlying ciliopathies.

PMID- 21862452
TI  - Increased levels of noisy splicing in cancers, but not for oncogene-derived
      transcripts.
AB  - Recent genome-wide analyses have detected numerous cancer-specific alternative
      splicing (AS) events. Whether transcripts containing cancer-specific AS events
      are likely to be translated into functional proteins or simply reflect noisy
      splicing, thereby determining their clinical relevance, is not known. Here we
      show that consistent with a noisy-splicing model, cancer-specific AS events
      generally tend to be rare, containing more premature stop codons and have less
      identifiable functional domains in both the human and mouse. Interestingly,
      common cancer-derived AS transcripts from tumour suppressor and oncogenes show
      marked changes in premature stop-codon frequency; with tumour suppressor genes
      exhibiting increased levels of premature stop codons whereas oncogenes have the
      opposite pattern. We conclude that tumours tend to have faithful oncogene
      splicing and a higher incidence of premature stop codons among tumour suppressor
      and cancer-specific splice variants showing the importance of considering
      splicing noise when analysing cancer-specific splicing changes.

PMID- 21862451
TI  - GWAS of butyrylcholinesterase activity identifies four novel loci, independent
      effects within BCHE and secondary associations with metabolic risk factors.
AB  - Serum butyrylcholinesterase (BCHE) activity is associated with obesity, blood
      pressure and biomarkers of cardiovascular and diabetes risk. We have conducted a
      genome-wide association scan to discover genetic variants affecting BCHE
      activity, and to clarify whether the associations between BCHE activity and
      cardiometabolic risk factors are caused by variation in BCHE or whether BCHE
      variation is secondary to the metabolic abnormalities. We measured serum BCHE in
      adolescents and adults from three cohorts of Australian twin and family studies.
      The genotypes from ~2.4 million single-nucleotide polymorphisms (SNPs) were
      available in 8791 participants with BCHE measurements. We detected significant
      associations with BCHE activity at three independent groups of SNPs at the BCHE
      locus (P = 5.8 * 10(-262), 7.8 * 10(-47), 2.9 * 10(-12)) and at four other loci:
      RNPEP (P = 9.4 * 10(-16)), RAPH1-ABI2 (P = 4.1 * 10(-18)), UGT1A1 (P = 4.0 * 10(
      8)) and an intergenic region on chromosome 8 (P = 1.4 * 10(-8)). These loci
      affecting BCHE activity were not associated with metabolic risk factors. On the
      other hand, SNPs in genes previously associated with metabolic risk had effects
      on BCHE activity more often than can be explained by chance. In particular, SNPs
      within FTO and GCKR were associated with BCHE activity, but their effects were
      partly mediated by body mass index and triglycerides, respectively. We conclude
      that variation in BCHE activity is due to multiple variants across the spectrum
      from uncommon/large effect to common/small effect, and partly results from
      (rather than causes) metabolic abnormalities.

PMID- 21862453
TI  - Genomic imprinting at a boundary element flanking the SDHD locus.
AB  - Germline mutations in SDHD, a mitochondrial complex II (succinate dehydrogenase)
      subunit gene at chromosome band 11q23, cause highly penetrant paraganglioma (PGL)
      tumors when transmitted through fathers. In contrast, maternal transmission
      rarely, if ever, leads to tumor development. The mechanism underlying this
      unusual monogenic tumor predisposition pattern is poorly understood. Here, we
      describe identification of imprinted methylation within an alternative promoter
      for a large intergenic non-coding RNA located at a distant gene desert boundary
      flanking SDHD. Methylation at this site primarily occurs within two consecutive
      HpaII restriction enzyme sites in a tissue-specific manner, most commonly in the
      adrenal gland. Informative fetal tissues and PGL tumors demonstrate maternal
      allelic hypermethylation. While a strong binding site for the enhancer-blocking
      protein CTCF within the alternative promoter shows no evidence of methylation,
      hyper-methylated adrenal tissues show increased binding of the chromatin-looping
      factor cohesin relative to the hypo-methylated tissues. These results suggest
      that the differential allelic methylation we observe at this locus is associated
      with altered chromatin architectures. These results provide molecular evidence
      for imprinting at a boundary element flanking the SDHD locus and suggest that
      epigenetic suppression of the maternal allele is the underlying mechanism of the
      imprinted penetrance of SDHD mutations.

PMID- 21862454
TI  - Effects of neutral pH and low-glucose degradation product-containing peritoneal
      dialysis fluid on systemic markers of inflammation and endothelial dysfunction: a
      randomized controlled 1-year follow-up study.
AB  - BACKGROUND: The local peritoneal effects of low-glucose degradation product (GDP)
      containing peritoneal dialysis fluid (PDF) have been extensively described.
      However, the systemic effects of prolonged prescription of these solutions are
      unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF
      on systemic inflammation and endothelial dysfunction markers in peritoneal
      dialysis (PD) patients. METHODS: This is a multicenter, open labeled, randomized
      controlled trial including one hundred fifty-two patients initiating continuous
      ambulatory peritoneal dialysis for end-stage renal disease from seven centers in
      Korea. Participants were randomly allocated to conventional PDF (Stay safe(r);
      Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance(r);
      Fresenius Medical Care) and were followed for 1 year. Primary outcome variable
      was the inflammation and endothelial dysfunction index (IEDI), a composite score
      derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1,
      soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C
      reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF),
      peritoneal membrane transport characteristics, ultrafiltration volume and
      nutritional parameters were measured as secondary outcome variables. RESULTS: Of
      152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered
      the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low
      GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to
      the conventional group; hs-CRP was not different between groups. Peritoneal
      transport characteristics, RRF, nutritional parameters, incidence of peritonitis
      and death-censored technique survival were not different between groups.
      CONCLUSION: Neutral pH and low-GDP PDF likely produce fewer changes in markers of
      endothelial dysfunction compared to conventional PDF in incident PD patients.

PMID- 21862455
TI  - Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti
      hypertensive and anti-proteinuric benefit of dietary sodium restriction and
      diuretics, but not angiotensin receptor blockade, in proteinuric renal patients.
AB  - BACKGROUND: Renin-angiotensin aldosterone system (RAAS) blockade only partly
      reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic
      kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet
      (LS) and/or diuretics] for optimal efficacy. However, both under- and
      overtitration of sodium targeting can easily occur. We evaluated whether N
      terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume
      expansion, predicts the benefits of sodium targeting in CKD patients. METHODS: In
      a cross-over randomized controlled trial, 33 non-diabetic CKD patients
      (proteinuria 3.8 +/- 0.4 g/24 h, blood pressure 143/86 +/- 3/2 mmHg, creatinine
      clearance 89 +/- 5 mL/min) were treated during 6-week periods with placebo,
      angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics
      (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 +/
      52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 +/- 62 mmol Na(+)/24 h, P <
      0.001 versus LS), in random order. As controls, 27 healthy volunteers were
      studied. RESULTS: NT-proBNP was elevated in patients during placebo + RS [90 (60
      137) versus 35 (27-45) pg/mL in healthy controls, P = 0.001]. NT-proBNP was
      lowered by LS, ARB and diuretics and was normalized by ARB + diuretic + LS [39
      (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit
      of normal (>125 pg/mL) predicted a larger reduction of blood pressure and
      proteinuria by LS and diuretics but not by ARB, during all steps of the titration
      regimen. CONCLUSIONS: Elevated NT-proBNP levels predict an enhanced anti
      hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS
      blockade, in proteinuric CKD patients. Importantly, this applies to the untreated
      condition, as well as to the subsequent treatment steps, consisting of RAAS
      blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a
      useful tool to identify CKD patients in whom sodium targeting can improve blood
      pressure and proteinuria.

PMID- 21862456
TI  - Increased risk of cancer in chronic dialysis patients: a population-based cohort
      study in Taiwan.
AB  - BACKGROUND: An increased incidence of cancer in chronic dialysis patients has not
      been confirmed in the Chinese population. The aim of this population-based study
      was to examine the risk of various types of cancers in chronic dialysis patients
      in Taiwan. METHODS: Data of 92 348 chronic dialysis patients extracted from the
      National Health Institutes Research Database during 1997-2008 were analyzed.
      Patients newly diagnosed with end-stage renal disease, free of cancer and
      receiving dialysis for >3 months were eligible for inclusion in the study.
      RESULTS: After a mean follow-up of 4.4 years, a new cancer was diagnosed in 4328
      chronic dialysis patients. The standardized incidence ratio (SIR) of chronic
      dialysis patients was 1.4 [95% confidence interval (CI): 1.3-1.4] and annual
      incidence of cancer was 1.1%. A trend of an increased SIR of cancer was observed
      in young patients and within the first year of dialysis. Bladder cancer carried
      the highest SIR (SIR: 8.2, 95% CI: 6.7-9.9) and had the highest frequency
      (21.2%). Importantly, the frequency (15.3%) of liver cancer was the second
      highest and the SIR (SIR: 1.4, 95% CI: 1.2-1.5) of liver cancer in chronic
      dialysis patients was higher than that of their healthy counterparts.
      Unexpectedly, chronic dialysis patients had a significantly reduced risk of
      developing lung cancer. CONCLUSION: Increased risk of cancer in chronic dialysis
      patients is confirmed in the Taiwanese population and it is necessary to develop
      different strategies for cancer screening in chronic dialysis patients among
      different ethnicities.

PMID- 21862457
TI  - Identification of lesions indicating rejection in kidney transplant biopsies:
      tubulitis is severely under-detected by conventional microscopy.
AB  - BACKGROUND: In the current international Banff classification of kidney
      transplant rejection, tubulitis and intimal arteritis are regarded as the key
      histological features of acute rejection. Grade 1 tubulitis can sometimes be seen
      in biopsies that do not represent acute rejection; but in the case of intimal
      arteritis, just one lymphocyte can justify anti-rejection treatment. Our aim was
      to audit reliability and accuracy of recognizing tubulitis and intimal arteritis
      using the approach recommended by the Banff classification and correlate any
      discrepancies with subsequent graft function. METHODS: This is a retrospective
      review of all kidney transplant biopsies reported as negative for rejection from
      1 January 2009 to 31 December 2009 to assess the presence or absence of occult
      tubulitis and arteritis. Lymphocytes were immunostained with CD3, using Periodic
      Acid Schiff as a counterstain. Sections were reviewed to detect missed intimal
      arteritis and tubulitis. Discrepancies between the report and the immunostain
      results were analysed by biopsy type and broken down by the reporting
      pathologist. The graft function of any patient with missed lesions was checked to
      test for adverse impact on the patient. RESULTS: 'Missed' tubulitis was found in
      68% of biopsies, but only two such cases subsequently developed biopsy-proven
      acute rejection. Only one case of missed intimal arteritis was found (1%) and the
      subsequent clinical course suggested that this was probably early rejection.
      There was no significant difference between the reporting pathologists.
      CONCLUSIONS: We conclude that tubulitis is missed very frequently, but the Banff
      classification seems to be 'calibrated' to allow for this and it does not
      seriously affect the identification of clinically significant acute rejection.
      Immunostaining is therefore not indicated in routine practice because (by Banff
      criteria) it would result in over-diagnosis of rejection. Intimal arteritis can
      indicate acute rejection even if extremely mild.

PMID- 21862458
TI  - The German Chronic Kidney Disease (GCKD) study: design and methods.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global
      health problem. The conditions leading to CKD, the health impact of CKD and the
      prognosis differ markedly between affected individuals. In particular, renal
      failure and cardiovascular mortality are competing risks for CKD patients.
      Opportunities for targeted intervention are very limited so far and require an
      improved understanding of the natural course of CKD, of the risk factors
      associated with various clinical end points and co-morbidities as well as of the
      underlying pathogenic mechanisms. METHODS: The German Chronic Kidney Disease
      (GCKD) study is a prospective observational national cohort study. It aims to
      enrol a total of 5000 patients with CKD of various aetiologies, who are under
      nephrological care, and to follow them for up to 10 years. At the time of
      enrolment, male and female patients have an estimated glomerular filtration rate
      (eGFR) of 30-60 mL/min*1.73 m2 or overt proteinuria in the presence of an eGFR>60
      mL/min*1.73 m2. Standardized collection of biomaterials, including DNA, serum,
      plasma and urine will allow identification and validation of biomarkers
      associated with CKD, CKD progression and related complications using hypothesis
      driven and hypothesis-free approaches. Patient recruitment and follow-up is
      organized through a network of academic nephrology centres collaborating with
      practising nephrologists throughout the country. CONCLUSIONS: The GCKD study will
      establish one of the largest cohorts to date of CKD patients not requiring renal
      replacement therapy. Similarities in its design with other observational CKD
      studies, including cohorts that have already been established in the USA and
      Japan, will allow comparative and joint analyses to identify important ethnic and
      geographic differences and to enhance opportunities for identification of
      relevant risk factors and markers.

PMID- 21862459
TI  - Dynamics of absolute amount of nephrin in a single podocyte in puromycin
      aminonucleoside nephrosis rats calculated by quantitative glomerular proteomics
      approach with selected reaction monitoring mode.
AB  - BACKGROUND: The slit diaphragm (SD) is a complex of podocyte-specific proteins
      and plays a significant role in glomerular filtration. To understand podocyte
      biology, it is important to determine the expression amount of the SD complex
      proteins. This study aimed to quantify the absolute amount of nephrin, which is
      believed to be a major component of SD, in podocytes and to apply that method to
      normal and puromycin aminonucleoside (PAN) nephrosis rats. METHODS: The counting
      method for podocyte number in a glomerulus was developed by three-dimensional
      reconstruction imaging of Wilms tumor (WT-1) immunofluorescence on isolated
      glomeruli. Absolute amount of nephrin was quantified by mass spectrometry using
      the selected reaction monitoring (SRM) mode with a stable isotope-labeled
      peptide. RESULTS: The number of podocytes per glomerulus was 95.5+/-17.6 in the
      control rats, 90.7+/-19.2 on Day 4 and 90.7+/-26.2 on Day 7 in PAN nephrosis
      rats. The amount of nephrin per glomerulus in control rats was 1.02+/-0.11 fmol
      and those in PAN nephrosis rats were reduced to 0.46+/-0.06 fmol and 0.35+/-0.04
      fmol on Day 4 and Day 7. The nephrin amount per podocyte was significantly
      decreased association with the development of proteinuria in PAN nephrosis rats.
      CONCLUSIONS: This study established the absolute quantification of nephrin and
      determined the amount of nephrin in a podocyte of normal and PAN nephrosis rat
      kidneys. This highly sensitive and selective quantification method for protein is
      a useful tool for the analysis of SD protein in a podocyte.

PMID- 21862460
TI  - Diffuse thin glomerular basement membrane in association with Fabry disease in a
      Chinese female patient.
AB  - We report a 41-year-old Chinese female with Fabry disease and diffuse thinning of
      the glomerular basement membrane (GBM). The patient presented with peripheral
      edema, mild proteinuria, microscopic hematuria, normal renal function,
      hypertension and tinnitus. Family screening showed that her daughter had
      microscopic hematuria, tinnitus and neuropathic pain. Renal biopsy of the proband
      showed focal segmental glomerulosclerosis with cytoplasmic vacuolization of the
      glomerular visceral epithelial cells by light microscopy. Laminated myelin
      inclusions in some of the glomerular podocytes, parietal epithelia, distal
      tubular epithelial cells and vascular endothelial cells along with diffuse
      thinning of the GBM (mean thickness of GBM: 216 +/- 31 nm) were identified by
      electron microscopy. Genetic analysis detected a de novo novel GLA mutation, 1208
      ins 21 bp, while a new variant of COL4A3 SNP M1209I was carried by mother and
      daughter as well as the proband's father (I-1) and one sister (II-4). The
      coexistence of thinned GBM should be considered in patients with Fabry disease
      manifested familial hematuria.

PMID- 21862461
TI  - Cardiovascular biomarkers and vascular function during childhood in the offspring
      of mothers with hypertensive disorders of pregnancy: findings from the Avon
      Longitudinal Study of Parents and Children.
AB  - AIMS: It is uncertain if the higher blood pressure (BP) observed in the offspring
      of hypertensive pregnancies is an isolated abnormality or one that is accompanied
      by impaired vascular function and alterations in lipid and inflammation markers
      that would be indicative of a more general cardiometabolic disturbance of the
      type observed in the mother during pre-eclampsia. METHODS AND RESULTS: In a large
      UK cohort of maternal-offspring pairs (n = 3537-4654), assessed at age 9-12
      years, we examined the associations of maternal gestational hypertension and pre
      eclampsia with offspring BP, endothelial function assessed by brachial artery
      flow-mediated dilatation; arterial stiffness assessed by carotid to radial pulse
      wave velocity; brachial artery distensibility and BP (vascular outcomes); as well
      as markers of inflammation, lipids and apolipoproteins A1 and B. Offspring of
      women with pre-eclampsia or gestational hypertension had higher systolic blood
      pressure by 2.04 mmHg (95% CI: 1.33, 2.76) and 1.82 mmHg (95% CI: 0.03, 3.62),
      respectively, and higher diastolic blood pressure by 1.10 mmHg (95% CI: 0.47,
      1.73) and 1.26 mmHg (95% CI: -0.32, 2.85), respectively, in analyses adjusted for
      maternal and offspring body mass index (BMI), offspring dietary sodium intake and
      other potential confounders. However, we found no associations of either
      hypertensive disorder of pregnancy with the other vascular outcomes or with
      inflammatory markers, lipids, and apolipoproteins. CONCLUSION: Pre-eclampsia and
      gestational hypertension are associated with higher offspring BP in childhood in
      the absence of other vascular alterations or metabolic derangements. The findings
      support the existence of shared mother-offspring risk factors that are specific
      for higher BP, rather than the additional cardiometabolic abnormalities of
      hypertensive disorder of pregnancy having long-term consequences for offspring.

PMID- 21862462
TI  - Relationship between discharge heart rate and mortality in patients after acute
      myocardial infarction treated with primary percutaneous coronary intervention.
AB  - AIMS: In patients with coronary artery disease, the prognostic value of heart
      rate has been mainly evaluated in patients with left ventricular dysfunction.
      Patients with ST-segment elevation acute myocardial infarction (STEMI) are
      currently treated with primary percutaneous coronary intervention (PCI) and in
      this contemporary population of patients, the relationship between heart rate and
      mortality during a follow-up >1 year has not been investigated. METHODS AND
      RESULTS: The population comprised 1453 STEMI patients treated with primary PCI.
      Resting heart rate was measured before discharge and all patients were followed
      prospectively. MAIN OUTCOME MEASURE: the endpoints were defined as all-cause
      mortality and cardiovascular mortality. The median follow-up duration was 40
      months. During this period, 83(6%) patients died of which 52(4%) died from
      cardiovascular disease. After adjusting for parameters reflecting a greater
      infarct size and the presence of heart failure, heart rate at discharge remained
      a strong predictor of mortality. Patients with a heart rate of >=70 b.p.m. had a
      two times increased risk of cardiovascular mortality at 1- and 4-year follow-up
      compared with patients with a heart rate <70 b.p.m.. In addition, every increase
      of 5 b.p.m. in heart rate at discharge was associated with a 29 and 24% increased
      risk of cardiovascular mortality at 1- and 4-year follow-up, respectively.
      CONCLUSION: In STEMI patients treated with primary PCI and optimal medical
      therapy, heart rate at discharge was an important predictor of mortality up to 4
      years follow-up even after adjustment for parameters reflecting a greater infarct
      size and the presence of heart failure.

PMID- 21862463
TI  - A primary cardiac paraganglioma.

PMID- 21862464
TI  - Cellular adaptive response to chronic radiation exposure in interventional
      cardiologists.
AB  - Aims Invasive cardiologists are the most exposed to ionizing radiation among
      health professionals and show an increased rate of somatic DNA damage. To
      evaluate the effects of chronic low-dose exposure to ionizing radiation on redox
      state and apoptotic activation.  Methods and results We enrolled 10 healthy
      exposed professionals (all interventional cardiologists, Group II, exposed: age =
      38 +/- 5 years) and 10 age- and gender-matched unexposed controls (Group I, non
      exposed). Exposed subjects had a median exposure of 4 mSv/year (range 1-8) by
      film badge dosimetry (below lead apron). We measured reduced glutathione (GSH, a
      marker of antioxidant response) in erythrocytes and plasma generation of hydrogen
      peroxide (a marker of oxyradical stress) by ferrous oxidation-xylenol orange
      assay in plasma. In both groups, lymphocytes were isolated and caspase-3 activity
      (a marker of apoptotic response) measured at baseline and following 2 Gy in vitro
      irradiation. Exposed subjects showed a three-fold increase in hydrogen peroxide
      (Group I = 2.21 +/- 1.03 vs. II = 6.51 +/- 1.55 MUM H(2)O(2) equivalents) and a
      1.7-fold increase in GSH (I = 12.37 +/- 1.22 vs. II = 20.61 +/- 2.16 mM). Exposed
      subjects also showed higher values of caspase-3 activity, both at baseline and
      more strikingly-following high-dose radiation challenge.  Conclusion In
      interventional cardiologists, chronic exposure to low-dose radiation is
      associated with an altered redox balance mirrored by an increase in hydrogen
      peroxide and with two possibly adaptive cellular responses: (i) an enhanced
      antioxidant defence (increase in GSH, counteracting increased oxyradical stress)
      and (ii) an increased susceptibility to apoptotic induction which might
      efficiently remove genetically damaged cells.

PMID- 21862465
TI  - Biological effects of low-dose radiation: of harm and hormesis.

PMID- 21862466
TI  - Review of bacterial and fungal culture and sensitivity results from reptilian
      samples submitted to a UK laboratory.
AB  - Reptiles are increasingly kept as pets in the UK and the majority of animals
      presented for veterinary attention have conditions with a bacterial basis, either
      as a primary infection or secondary to husbandry deficiencies. Culture and
      sensitivity tests can provide useful information for selecting treatment
      protocols, but the lack of published data reviewing the normal reptilian
      microflora means interpretation of results is subjective. This study publishes
      the results of culture and sensitivity results from all reptilian samples
      provided to a commercial pathology laboratory over a 24-month period and compares
      these data with the published literature to assist clinicians to determine
      appropriate treatment protocols. Results provided a wide range of cultured
      organisms, although trends were seen for varying anatomical locations, species
      and time of year. In addition, antibiotic sensitivity revealed some concerning
      trends.

PMID- 21862467
TI  - Clinical syndromes associated with the circulation of multiple serotypes of
      bluetongue virus in dairy cattle in Israel.
AB  - From 2008 to 2011, seven distinct bluetongue virus (BTV) serotypes (BTV-2, BTV-4,
      BTV-5, BTV-8, BTV-15, BTV-16 and BTV-24) have been identified to be circulating
      in diseased sheep and cattle in Israel. This paper describes the array of
      clinical manifestations caused by BTV in cattle in Israel. Each set of clinical
      manifestations has been categorised as a syndrome and six distinct clinical
      syndromes have been observed in dairy cattle: 'footrot-like syndrome', 'sore nose
      syndrome', 'subcutaneous emphysema syndrome', 'red/rough udder syndrome',
      'bluetongue/epizootic haemorrhagic disease systemic syndrome' and 'maladjustment
      syndrome'.

PMID- 21862468
TI  - Abdominal radiographic and ultrasonographic findings in ferrets (Mustela putorius
      furo) with systemic coronavirus infection.
AB  - Ferret systemic coronavirus infection (FSCV) is a systemic disease in ferrets
      that clinically and pathologically resembles the dry form of FIP. The present
      study describes abdominal imaging features of 11 ferrets with FSCV. Abdominal
      survey radiographs were available for eight ferrets and ultrasound examination
      for all cases. Loss of lumbar musculature, decreased peritoneal detail, presence
      of mid-abdominal soft-tissue masses and splenomegaly were the most significant
      radiographic signs in these patients. Ultrasonographic findings including
      peritonitis, abdominal lymphadenopathy, splenomegaly, abdominal soft-tissue
      masses, nephromegaly and changes in the renal cortex echogenicity were recorded
      in the majority of cases with FSCV. As an imaging modality, ultrasound is
      superior to radiology when abdominal contrast is reduced, as it frequently occurs
      in these cases. However, although imaging techniques provide additional
      information in the antemortem diagnosis, they can not replace the definitive
      diagnosis based on histological and immunohistochemical results.

PMID- 21862469
TI  - Influence of housing system and design on bone strength and keel bone fractures
      in laying hens.
AB  - The main objectives of the study were to provide an accurate assessment of
      current levels of old breaks in end-of-lay hens housed in a variety of system
      designs and identify the important risk factors. Sixty-seven flocks housed in
      eight broad subcategories were assessed at the end of the production period.
      Within each flock, the presence of keel fractures was determined and the tibia,
      humerus and keel bones dissected for measurement of breaking strength. For each
      house, variations in internal design and perching provision were categorised and
      the effective heights of the differing structures recorded. All systems were
      associated with alarmingly high levels of keel damage although variation in mean
      prevalence between systems was evident with flocks housed in furnished cages
      having the lowest prevalence (36 per cent) despite also having significantly
      weaker bones and flocks housed in all systems equipped with multilevel perches
      showing the highest levels of damage (over 80 per cent) and the highest severity
      scores.

PMID- 21862470
TI  - Reducing the oxygen concentration of gases delivered from anaesthetic machines
      unadapted for medical air.
AB  - High fractional concentrations of inspired oxygen (FiO(2)) delivered over
      prolonged periods produce characteristic histological changes in the lungs and
      airway of exposed animals. Modern medical anaesthetic machines are adapted to
      deliver medical air (FiO(2)=0.21) for the purpose of reducing FiO(2); anaesthetic
      machines designed for the veterinary market have not been so adapted. Two
      inexpensive modifications that allow medical air to be added to the gas flow from
      veterinary anaesthetic machines are described. The advantages and disadvantages
      of each modification are discussed.

PMID- 21862471
TI  - Effects of exercise and human contact on animal welfare in a dog shelter.
AB  - The aim of the study is to investigate the reduction of stress in dogs in
      municipal shelters through easy-to-implement activities, ie, 25-minute sessions
      of exercise and human contact, that do not require a significant investment in
      terms of funding, staff or time. The results demonstrate that the dogs taking
      part in these sessions have lower salivary cortisol levels (F=121.42; P<0.05) and
      achieve better scores on a behaviour test (t(17)=4.27; P=0.001). It can therefore
      be affirmed that the exercise and human contact protocol proposed in the present
      study diminishes stress and improves the welfare of dogs housed in shelters.

PMID- 21862472
TI  - Effects of transportation on expression of Hsp90, Hsp70, Hsp27 and alphaB
      crystallin in the pig stomach.
AB  - Twenty pigs were randomly divided into four groups based on the amount of time
      spent in transport (zero, one, two or four hours). Pathological examination of
      all transported pigs showed that exfoliation of chief cells from the gastric
      surface occurred in pigs during transportation. These results imply that
      integrity of the gastric mucosa was compromised by damage occurring during the
      four-hour transportation, despite the fact that gastric ulcers were not present.
      Levels of Hsp90 expression in stomach tissues were significantly decreased
      (P<0.01) after two-hour transportation, but Hsp70 levels increased significantly
      (P<0.05) after one, two and four hours of transportation. Hsp27 levels remained
      relatively stable independent of the length of transport. Levels of alphaB
      crystallin expression in the stomach were significantly increased (P<0.05) after
      four hours of transportation. Variations in Hsp90, Hsp70, Hsp27 and alphaB
      crystallin levels suggest that distinct protective functions are modulated by
      different Hsps in stomach tissues during transportation. Alterations in Hsp70 and
      alphaB-crystallin expression appear to be associated with protective functions,
      as no apparent gastric ulcers were present in pigs that underwent four hours of
      transportation. Levels of heat shock transcription factor-1, which regulate the
      expression of Hsps, remained relatively stable independent of the transportation
      period.

PMID- 21862473
TI  - Variation in gentamicin and vancomycin dosage and monitoring in UK neonatal
      units.
AB  - BACKGROUND: Gentamicin and vancomycin are commonly used in neonatal units for the
      treatment of life-threatening infections. This study aimed to describe the dosage
      regimen and the approach to therapeutic drug monitoring (TDM) for both
      antibiotics in units that participate in a UK neonatal network. METHODS:
      Questionnaires were sent to all units across the Extended Neonatal Network,
      requesting details of each unit's dosing regimen and TDM practice. RESULTS: A
      total of 43 (of 114) units replied to the gentamicin questionnaire and 29 to the
      vancomycin questionnaire. Ten different gentamicin dosing regimens were used,
      depending on gestational age and weight. Most units (79%) followed British
      National Formulary for Children dosing guidance regarding vancomycin, but there
      were nine variations in TDM practice. CONCLUSIONS: There is significant variation
      in gentamicin and vancomycin dosing regimens and TDM guidance across a UK network
      of neonatal units. The development of standardized, evidence-based protocols
      should be prioritized.

PMID- 21862474
TI  - Indolone-N-oxide derivatives: in vitro activity against fresh clinical isolates
      of Plasmodium falciparum, stage specificity and in vitro interactions with
      established antimalarial drugs.
AB  - OBJECTIVES: Indolone-N-oxides are characterized by the presence of a highly
      reactive pharmacophore, the nitrone moiety (C=N(+)-O(-)), which undergoes
      oxidation-reduction reactions. The aims of the present study were to: (i)
      evaluate the in vitro activity of the parent compound, designated as compound 1,
      against 34 fresh clinical isolates of Plasmodium falciparum; (ii) compare the
      activity of compound 1 with that of chloroquine and dihydroartemisinin to assess
      the potential for cross-resistance; (iii) investigate drug interactions of
      indolone-N-oxides with standard antimalarials; and (iv) determine the stage
      dependent activity of indolone-N-oxides. METHODS: In vitro antimalarial activity
      was evaluated against clinical isolates collected from Cameroonian patients by
      the [(3)H]hypoxanthine incorporation assay. In vitro interactions between
      compound 1 or another analogue, compound 4, and established antimalarial drugs
      were assessed by the fixed ratio method. Stage specificity was evaluated by light
      microscopy using highly synchronized P. falciparum cultures. RESULTS: The
      geometric mean 50% inhibitory concentration (IC(50)) of compound 1 was 48.6 nM.
      Its activity did not differ between the chloroquine-susceptible and the
      chloroquine-resistant isolates. There was no correlation between chloroquine and
      compound 1 responses (r = 0.015; P > 0.05), but the in vitro responses of
      compound 1 and dihydroartemisinin were significantly and positively correlated (r
      = 0.444; P < 0.05). No significant in vitro interaction was observed between
      indolone-N-oxide derivatives and established antimalarial drugs (artemisinin and
      its derivatives, chloroquine, amodiaquine, quinine and mefloquine). Compound 1
      and compound 4, as well as artesunate, inhibited parasite maturation at the ring
      stage. CONCLUSIONS: These findings suggest that other indolone-N-oxide
      derivatives with more potent activity than the parent compound may hold promise
      as antimalarials in the future.

PMID- 21862475
TI  - Comment on: Efficacy and safety of tigecycline: a systematic review and meta
      analysis.

PMID- 21862476
TI  - Interspecies dissemination of a novel class 1 integron carrying blaIMP-19 among
      Acinetobacter species in Japan.
AB  - OBJECTIVES: To analyse the dissemination of metallo-beta-lactamase genes and
      mobile genetic elements among Acinetobacter spp. METHODS: From January 2004 to
      December 2010, 16 Acinetobacter isolates that were positive for metallo-beta
      lactamase production were collected and analysed. Antimicrobial susceptibilities
      were studied, and molecular typing was performed using PFGE and multilocus
      sequence typing (MLST). The resistance genes, including carbapenemase-encoding
      genes and aminoglycoside resistance genes, were detected by PCR. Mobile genetic
      elements were identified by nucleotide sequence analysis and PCR mapping of the
      integron gene cassettes and the insertion sequence (IS) elements. RESULTS: We
      identified 10 Acinetobacter genospecies 3 isolates that belonged to three PFGE
      clusters and four MLST types, 4 Acinetobacter johnsonii isolates that belonged to
      the same PFGE cluster, 1 Acinetobacter baumannii isolate and 1 Acinetobacter
      junii isolate. Each isolate was not susceptible to at least one carbapenem. The
      bla(IMP-19) gene was found in two PFGE clusters of genospecies 3, in the one PFGE
      cluster of A. johnsonii and in each of the A. baumannii and A. junii isolates,
      and was located in a class 1 integron as a gene cassette array of bla(IMP-19)
      aac(6')-31-bla(OXA-21)-aadA1. One genospecies 3 isolate harboured bla(IMP-11),
      bla(OXA-58). This isolate harboured three mobile elements, including a class 1
      integron that carried bla(IMP-11), another class 1 integron that carried catB8
      like/aacA4-aadA5 and an IS element (bla(OXA-58) flanked an either side by
      ISAba3). CONCLUSIONS: We demonstrated that the bla(IMP-19) gene carried in the
      novel class 1 integron gene cassette array of bla(IMP-19)-aac(6')-31-bla(OXA-21)
      aadA1 has been horizontally disseminated among different Acinetobacter spp.
      Additionally, one isolate harboured multiple mobile genetic elements.

PMID- 21862477
TI  - Molecular epidemiology of extraintestinal pathogenic Escherichia coli isolates
      from a regional cohort of elderly patients highlights the prevalence of ST131
      strains with increased antimicrobial resistance in both community and hospital
      care settings.
AB  - OBJECTIVES: To assess the molecular epidemiology and prevalence of antibiotic
      resistance in Escherichia coli causing urinary tract infections of elderly
      patients from community and hospital settings. Also, to determine whether the
      possession of antibiotic resistance and virulence-associated genes can be linked
      to patient location or the clonal group of the organisms in question. METHODS: E.
      coli were isolated from the urine samples of elderly patients from the Nottingham
      area, and subjected to antibiotic susceptibility testing, virulence gene
      detection by PCR and multilocus sequence typing. RESULTS: No correlation was
      observed between community- or hospital-derived strains with regard to antibiotic
      resistance levels or virulence gene profiles. E. coli ST131 (where ST stands for
      sequence type) was the predominant ST found in both hospital and community
      samples, and demonstrated high levels of antibiotic resistance to the test panel,
      but did not possess a significantly larger array of virulence genes or a specific
      gene profile compared with other STs. CONCLUSIONS: The level of antibiotic
      resistance or virulence gene possession in uropathogenic E. coli is not directly
      associated with the healthcare setting of the patient, but there is a variation
      in antibiotic resistance and virulence gene possession depending on clonal group.
      ST131 is highly virulent and demonstrates high levels of antibiotic resistance,
      but its virulence does not appear to be attributable to the possession of a
      specific virulence-associated gene set or the possession of any virulence
      associated gene in significantly higher levels than in any other ST.

PMID- 21862478
TI  - Flowering time variation in oilseed rape (Brassica napus L.) is associated with
      allelic variation in the FRIGIDA homologue BnaA.FRI.a.
AB  - Oilseed rape (Brassica napus L.) is a major oil crop which is grown worldwide.
      Adaptation to different environments and regional climatic conditions involves
      variation in the regulation of flowering time. Winter types have a strong
      vernalization requirement whereas semi-winter and spring types have a low
      vernalization requirement or flower without exposure to cold, respectively. In
      Arabidopsis thaliana, FRIGIDA (FRI) is a key regulator which inhibits floral
      transition through activation of FLOWERING LOCUS C (FLC), a central repressor of
      flowering which controls vernalization requirement and response. Here, four FRI
      homologues in B. napus were identified by BAC library screening and PCR-based
      cloning. While all homologues are expressed, two genes were found to be
      differentially expressed in aerial plant organs. One of these, BnaA.FRI.a, was
      mapped to a region on chromosome A03 which co-localizes with a major flowering
      time quantitative trait locus in multiple environments in a doubled-haploid
      mapping population. Association analysis of BnaA.FRI.a revealed that six SNPs,
      including at least one at a putative functional site, and one haplotype block,
      respectively, are associated with flowering time variation in 248 accessions,
      with flowering times differing by 13-19 d between extreme haplotypes. The results
      from both linkage analysis and association mapping indicate that BnaA.FRI.a is a
      major determinant of flowering time in oilseed rape, and suggest further that
      this gene also contributes to the differentiation between growth types. The
      putative functional polymorphisms identified here may facilitate adaptation of
      this crop to specific environments through marker-assisted breeding.

PMID- 21862479
TI  - Lignin metabolism has a central role in the resistance of cotton to the wilt
      fungus Verticillium dahliae as revealed by RNA-Seq-dependent transcriptional
      analysis and histochemistry.
AB  - The incompatible pathosystem between resistant cotton (Gossypium barbadense cv.
      7124) and Verticillium dahliae strain V991 was used to study the cotton
      transcriptome changes after pathogen inoculation by RNA-Seq. Of 32,774 genes
      detected by mapping the tags to assembly cotton contigs, 3442 defence-responsive
      genes were identified. Gene cluster analyses and functional assignments of
      differentially expressed genes indicated a significant transcriptional
      complexity. Quantitative real-time PCR (qPCR) was performed on selected genes
      with different expression levels and functional assignments to demonstrate the
      utility of RNA-Seq for gene expression profiles during the cotton defence
      response. Detailed elucidation of responses of leucine-rich repeat receptor-like
      kinases (LRR-RLKs), phytohormone signalling-related genes, and transcription
      factors described the interplay of signals that allowed the plant to fine-tune
      defence responses. On the basis of global gene regulation of phenylpropanoid
      metabolism-related genes, phenylpropanoid metabolism was deduced to be involved
      in the cotton defence response. A closer look at the expression of these genes,
      enzyme activity, and lignin levels revealed differences between resistant and
      susceptible cotton plants. Both types of plants showed an increased level of
      expression of lignin synthesis-related genes and increased phenylalanine-ammonia
      lyase (PAL) and peroxidase (POD) enzyme activity after inoculation with V.
      dahliae, but the increase was greater and faster in the resistant line.
      Histochemical analysis of lignin revealed that the resistant cotton not only
      retains its vascular structure, but also accumulates high levels of lignin.
      Furthermore, quantitative analysis demonstrated increased lignification and cross
      linking of lignin in resistant cotton stems. Overall, a critical role for lignin
      was believed to contribute to the resistance of cotton to disease.

PMID- 21862480
TI  - VpRFP1, a novel C4C4-type RING finger protein gene from Chinese wild Vitis
      pseudoreticulata, functions as a transcriptional activator in defence response of
      grapevine.
AB  - RING finger proteins comprise a large family and play important roles in
      regulation of growth and development, hormone signalling, and responses to biotic
      and abiotic stresses in plants. In this study, the identification and functional
      characterization of a C4C4-type RING finger protein gene from the Chinese wild
      grapevine Vitis pseudoreticulata (designated VpRFP1) are reported. VpRFP1 was
      initially identified as an expressed sequence tag (EST) from a cDNA library
      constructed from leaves of V. pseudoreticulata inoculated with the grapevine
      powdery mildew Uncinula necator. Sequence analysis of the deduced VpRFP1 protein
      based on the full-length cDNA revealed an N-terminal nuclear localization signal
      (NLS) and a C-terminal C4C4-type RING finger motif with the consensus sequence
      Cys-X(2)-Cys-X(13)-Cys-X(1)-Cys-X(4)-Cys-X(2)-Cys-X(10)-Cys-X(2)-Cys. Upon
      inoculation with U. necator, expression of VpRFP1 was rapidly induced to higher
      levels in mildew-resistant V. pseudoreticulata plants. In contrast, expression of
      VpRFP1 was down-regulated in mildew-susceptible V. vinifera plants. Western
      blotting using an antibody raised against VpRFP1 showed that VpRFP1 was also
      induced to higher levels in V. pseudoreticulata plants at 12-48 hours post
      inoculation (hpi). However, there was only slight increase in VpRFP in V.
      vinifera plants in the same time frame, even though a more significant increase
      was observed at 96-144 hpi in these plants. Results from transactivation assays
      in yeast showed that the RING finger motif of VpRFP1 exhibited some activity of
      transcriptional activation; however, no activity was seen with the full-length
      VpRFP1. Overexpression of VpRFP1 in Arabidopsis plants was found to enhance
      resistance to Arabidopsis powdery mildew Golovinomyces cichoracearum, which
      seemed to be correlated with increased transcript levels of AtPR1 and AtPR2 in
      the pathogen-infected tissues. In addition, the Arabidopsis transgenic lines
      showed enhanced resistance to a virulent bacterial pathogen Pseudomonas syringae
      pv. tomato DC3000. Taken together, the results suggested that VpRFP1 may be a
      transcriptional activator of defence-related genes in grapevines.

PMID- 21862481
TI  - A jacalin-related lectin-like gene in wheat is a component of the plant defence
      system.
AB  - Jacalin-related lectins (JRLs) are a subgroup of proteins with one or more
      jacalin-like lectin domains. Although JRLs are often associated with biotic or
      abiotic stimuli, their biological functions in plants, as well as their
      relationships to plant disease resistance, are poorly understood. A mannose
      specific JRL (mJRL)-like gene (TaJRLL1) that is mainly expressed in stem and
      spike and encodes a protein with two jacalin-like lectin domains was identified
      in wheat. Pathogen infection and phytohormone treatments induced its expression;
      while application of the salicylic acid (SA) biosynthesis inhibitor paclobutrazol
      and the jasmonic acid (JA) biosynthesis inhibitor diethyldithiocarbamic acid,
      respectively, substantially inhibited its expression. Attenuating TaJRLL1 through
      virus-induced gene silencing increased susceptibility to the facultative fungal
      pathogen Fusarium graminearum and the biotrophic fungal pathogen Blumeria
      graminis. Arabidopsis thaliana transformed with TaJRLL1 displayed increased
      resistance to F. graminearum and Botrytis cinerea. JA and SA levels in transgenic
      Arabidopsis increased significantly. A loss or increase of disease resistance due
      to an alteration in TaJRLL1 function was correlated with attenuation or
      enhancement of the SA- and JA-dependent defence signalling pathways. These
      results suggest that TaJRLL1 could be a component of the SA- and JA-dependent
      defence signalling pathways.

PMID- 21862482
TI  - Characterization of a dual-affinity nitrate transporter MtNRT1.3 in the model
      legume Medicago truncatula.
AB  - Primary root growth in the absence or presence of exogenous NO(3)(-) was studied
      by a quantitative genetic approach in a recombinant inbred line (RIL) population
      of Medicago truncatula. A quantitative trait locus (QTL) on chromosome 5 appeared
      to be particularly relevant because it was seen in both N-free medium (LOD score
      5.7; R(2)=13.7) and medium supplied with NO(3)(-) (LOD score, 9.5; R(2)=21.1)
      which indicates that it would be independent of the general nutritional status.
      Due to its localization exactly at the peak of this QTL, the putative NRT1-NO(3)(
      ) transporter (Medtr5g093170.1), closely related to Arabidopsis AtNRT1.3, a
      putative low-affinity nitrate transporter, appeared to be a significant candidate
      involved in the control of primary root growth and NO(3)(-) sensing. Functional
      characterization in Xenopus oocytes using both electrophysiological and
      (15)NO(3)(-) uptake approaches showed that Medtr5g093170.1, named MtNRT1.3,
      encodes a dual-affinity NO(3)(-) transporter similar to the AtNRT1.1
      'transceptor' in Arabidopsis. MtNRT1.3 expression is developmentally regulated in
      roots, with increasing expression after completion of germination in N-free
      medium. In contrast to members of the NRT1 superfamily characterized so far,
      MtNRT1.3 is environmentally up-regulated by the absence of NO(3)(-) and down
      regulated by the addition of the ion to the roots. Split-root experiments showed
      that the increased expression stimulated by the absence of NO(3)(-) was not the
      result of a systemic signalling of plant N status. The results suggest that
      MtNRT1.3 is involved in the response to N limitation, which increases the ability
      of the plant to acquire NO(3)(-) under N-limiting conditions.

PMID- 21862483
TI  - Distribution of naphthoquinones, plumbagin, droserone, and 5-O-methyl droserone
      in chitin-induced and uninduced Nepenthes khasiana: molecular events in prey
      capture.
AB  - Prey capture and digestion in Nepenthes spp. through their leaf-evolved
      biological traps involve a sequence of exciting events. Sugar-rich nectar, aroma
      chemicals, narcotic alkaloid secretions, slippery wax crystals, and other
      biochemicals take part in attracting, capturing, and digesting preys in Nepenthes
      pitchers. Here we report the distribution of three potent naphthoquinones in
      Nepenthes khasiana and their roles in prey capture. Plumbagin was first detected
      in N. khasiana, and its content (root: 1.33 +/- 0.02%, dry wt.) was the highest
      found in any natural source. Chitin induction enhanced plumbagin levels in N.
      khasiana (root: 2.17 +/- 0.02%, dry wt.). Potted N. khasiana plants with limited
      growth of roots and aerial parts, showed higher levels of plumbagin accumulation
      (root: 1.92 +/- 0.02%; root, chitin induction: 3.30 +/- 0.21%, dry wt.) compared
      with field plants. Plumbagin, a known toxin, insect ecdysis inhibitor, and
      antimicrobial, was also found embedded in the waxy layers at the top prey capture
      region of N. khasiana pitchers. Chitin induction, mimicking prey capture,
      produced droserone and 5-O-methyl droserone in N. khasiana pitcher fluid. Both
      these naphthoquinone derivatives provide antimicrobial protection to the pitcher
      fluid from visiting preys. A two-way barrier was found between plumbagin and its
      two derivatives. Plumbagin was never detected in the pitcher fluid whereas both
      its derivatives were only found in the pitcher fluid on chitin induction or prey
      capture. The three naphthoquinones, plumbagin, droserone, and 5-O-methyl
      droserone, act as molecular triggers in prey capture and digestion in the
      carnivorous plant, N. khasiana.

PMID- 21862484
TI  - The cytoskeleton in plasmodesmata: a role in intercellular transport?
AB  - Actin and myosin are components of the plant cell cytoskeleton that extend from
      cell to cell through plasmodesmata (PD), but it is unclear how they are organized
      within the cytoplasmic sleeve or how they might behave as regulatory elements.
      Early work used antibodies to locate actin and myosin to PD, at the electron
      microscope level, or to pitfields (aggregations of PD in the cell wall), using
      immunofluorescence techniques. More recently, a green fluorescent protein (GFP)
      tagged plant myosin VIII was located specifically at PD-rich pitfields in cell
      walls. Application of actin or myosin disrupters may modify the conformation of
      PD and alter rates of cell-cell transport, providing evidence for a role in
      regulating PD permeability. Intriguingly, there is now evidence of
      differentiation between types of PD, some of which open in response to both actin
      and myosin disrupters, and others which are unaffected by actin disrupters or
      which close in response to myosin inhibitors. Viruses also interact with elements
      of the cytoskeleton for both intracellular and intercellular transport. The
      precise function of the cytoskeleton in PD may change during cell development,
      and may not be identical in all tissue types, or even in all PD within a single
      cell. Nevertheless, it is likely that actin- and myosin-associated proteins play
      a key role in regulating cell-cell transport, by interacting with cargo and
      loading it into PD, and may underlie the capacity for one-way transport across
      particular cell and tissue boundaries.

PMID- 21862485
TI  - Temperature rather than photoperiod controls growth cessation and dormancy in
      Sorbus species.
AB  - Environmental regulation of growth and dormancy of four Sorbus genotypes was
      studied in controlled environments. Emphasis was placed on assessment of the
      presence and nature of the deficient photoperiodic dormancy regulation system
      that has previously been reported for some woody Rosaceae species. Two genotypes
      of Sorbus aucuparia L. maintained indeterminate growth for 8 weeks and 9 weeks at
      temperatures of 15  degrees C and 21  degrees C in both 20 h and 10 h
      photoperiods, while at 9  degrees C, in the same photoperiodic conditions, they
      immediately ceased growing. At the higher temperatures, initiation of new leaves
      (nodes) was unaffected by photoperiod, while internode elongation was
      significantly enhanced by long days (LD). However, even after prolonged exposure
      to 9  degrees C, most plants resumed growth when moved to high temperature and
      LD, indicating a shallow state of dormancy. Seedlings of Sorbus intermedia (J. F.
      Ehrh.) Pers. and micro-propagated plantlets of S. commixta Hedl. 'Dodong' were
      also unaffected by photoperiod during primary growth, but failed to elongate and
      gradually became dormant regardless of temperature and day-length conditions.
      However, after chilling and breaking of dormancy, the plants elongated vigorously
      but changed to a determinate mode of growth. Furthermore, a temperature of 9 
      degrees C was found to be fully effective for breaking dormancy in S. intermedia
      plants. It is concluded that deficient photoperiodic dormancy control seems
      widespread in the Rosaceae and that, in such plants, both dormancy induction and
      release is brought about by low temperature. The potential impacts of climate
      change on such trees are discussed.

PMID- 21862486
TI  - Childhood psychopathology at age 8 predicts antidepressant use by age 24.

PMID- 21862487
TI  - Vascular patterns of brain tumors.
AB  - Multiple vascular patterns are presented in tumors of the central nervous system
      (CNS), including microvascular hyperplasia, branching capillaries, numerous
      capillaries without definite pattern, hyalinized vessels, and angiomatous area.
      These vascular patterns play important roles in pathological diagnosis of brain
      tumors. Because of insufficient recognition of the significance of the various
      vascular patterns, only a few of them have been applied in pathological
      diagnosis, leading to missed diagnosis and diagnostic errors. Microvascular
      hyperplasia can present in multiple brain tumors but display different diagnostic
      values. Otherwise, varied brain tumors characterized by branching capillaries or
      vascular pattern mimicking branching capillaries should be given careful
      consideration. Therefore, a familiarity of these tumors and their vascular
      pattern is essential for general pathologists. This study reviews the value of
      various kinds of vascular patterns for pathological diagnosis of brain tumors,
      constructs a framework for better understanding, and provides a novel perspective
      for general pathologists.

PMID- 21862488
TI  - Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a clinicopathological
      study of 79 cases.
AB  - BACKGROUND: Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a
      benign lesion that can present as a palpable nodule or as an incidental finding
      in breast biopsies. DESIGN: The study comprised 79 cases diagnosed at Loyola
      University Medical Center from 2002 to 2009. The pathology slides were reviewed
      to document the distribution, type, and association with preneoplastic or
      neoplastic epithelial lesions. Z-test for independent proportions is used for
      analysis. RESULTS: A total of 76 patients were female and 3 were male. In all,
      59.8% of patients presented with a breast mass and in 40.2% the lesion was an
      incidental finding. Classical PASH morphology was seen in 97.6% and proliferative
      PASH in 2.4%. Associated epithelial lesions were benign proliferative changes in
      60.4%, atypical ductal and atypical lobular hyperplasia in 25.6% and infiltrating
      carcinoma in 11% of cases. CONCLUSIONS: Based on these results, extensive
      sampling of biopsy specimen with PASH and appropriate clinical and radiologic
      follow-up is recommended.

PMID- 21862489
TI  - Aggressive angiomyxoma admixed with endometriosis: a case report.
AB  - Aggressive angiomyxoma and endometriosis are two apparently unrelated lesions
      which commonly arise within the pelvis. However, whilst their simultaneous
      occurrence in this site may be fortuitous, a shared pathogenesis cannot be
      entirely excluded.

PMID- 21862490
TI  - Head and neck mucosal malignant melanoma: clinicopathologic correlation with
      contemporary review of prognostic indicators.
AB  - Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas
      (HNMM) behave much more aggressively and their prognostic markers have not been
      fully elucidated. Therefore, the aim of this study was to review the
      clinicopathologic features of a contemporary series of primary HNMM, retrieved
      from archival material of 2 large medical centers, and to explore the
      association, if any, between these variables, the clinical features, and
      outcomes. The clinicopathologic, radiographic, and follow-up information as well
      as the dominant histologic pattern, mitotic rate, presence/absence of
      pigmentation, necrosis, ulceration, vascular invasion, and host-associated
      lymphocytic response were retrieved and recorded. Twenty cases were identified
      including 1 melanoma in situ. Eight-five percent of tumors arose in the sinonasal
      tract and 3 (15%) in the oral cavity. After a median follow-up of 25 months, all
      patients with invasive melanoma developed recurrence and/or metastasis. Local
      recurrences occurred in 82% of the patients after a median of 12 months, and
      distant metastasis occurred in 71% of the patients after a median of 13 months.
      Of those with adequate follow-up, 82% died with disease, and the remaining 3 had
      recurrent or metastatic disease. Fourth-seven percent of tumors were pigmented,
      89% showed at least focal necrosis, and 93% demonstrated ulceration. Sixth-eight
      percent showed vascular invasion and 63% had a brisk host lymphocytic response.
      Mitotic rates ranged from 2 to 60/10 high-power fields. The absence of an
      invasive component might be associated with a better prognosis but other clinical
      and pathological features that predict outcome, and/or could influence therapy,
      remain to be determined in HNMM.

PMID- 21862491
TI  - Nodular histiocytic and mesothelial hyperplasia.

PMID- 21862492
TI  - Estimation of teeth-to-vallecula distance for prediction of optimal oropharyngeal
      airway length in young children.
AB  - BACKGROUND: Estimation of teeth-to-vallecula distance would facilitate the
      selection of properly sized oropharyngeal airways in young children. The aims of
      the present study were to measure the teeth-to-vallecula distance and to create
      an algorithm to predict this distance based on anatomical landmarks and patient
      characteristics in children. METHODS: Two hundred children, aged 1-9 yr,
      undergoing elective surgery were investigated. After induction of general
      anaesthesia, the distance from the teeth to the vallecula was measured using a
      laryngoscope with a straight blade. After intubation, the distances from the
      mouth angle to the mandible angle and the tragus of the ear were measured with a
      tape measure. RESULTS: The teeth-to-vallecula distance was significantly
      correlated with the age, weight, height, and external measurements (P<0.001). By
      stepwise multiple linear regression analysis, a formula was obtained for the
      teeth-to-vallecula distance (cm) = 3.998 + 0.017 * age (months)+the mouth-to
      mandible distance * 0.286 with a high coefficient of determination (r2=0.764).
      CONCLUSIONS: The teeth-to-vallecula distance can be predicted using the age and
      the mouth-to-mandible distance in young children.

PMID- 21862493
TI  - Influence of haemorrhage on the pseudo-steady-state remifentanil concentration in
      a swine model: a comparison with propofol and the effect of haemorrhagic shock
      stage.
AB  - BACKGROUND: The increase in remifentanil concentration during haemorrhagic shock
      and the difference between this effect and that for propofol are not fully
      understood. We investigated the influence of haemorrhage on the pseudo-steady
      state remifentanil concentration in a porcine model and compared the changes with
      those for propofol. METHODS: After infusion of remifentanil (0.5 ug kg-1 min-1)
      and propofol (6 mg kg-1 h-1 after 2 mg kg-1 bolus infusion) for 60 min, nine
      swine [mean (standard deviation) body weight=26.3 (1.3) kg] were studied using a
      stepwise haemorrhage model (10% of estimated blood volume removed every 30 min
      until 1.5 h, and stepwise removal of 5% every 30 min thereafter until circulatory
      collapse). Haemodynamic and metabolic variables and plasma remifentanil and
      propofol concentrations were measured at every step. RESULTS: A mean volume of
      913 (82) ml of blood was drained before reaching circulatory collapse. The
      increases in plasma concentrations from the prehaemorrhagic value fitted the
      following equations: % increase in remifentanil=2.1 * cumulative blood loss (% of
      initial blood volume) and % increase in propofol = 0.7 * cumulative blood loss
      during compensated shock; and % increase in remifentanil = 27.4 * cumulative
      blood loss-897 and % increase in propofol = 9.5 * cumulative blood loss-306
      during uncompensated shock. Remifentanil concentrations were highly correlated
      with the reciprocal of cardiac output. CONCLUSIONS: During haemorrhage, the
      plasma remifentanil concentration showed a three-fold greater increase than that
      of propofol in administration by continuous infusion.

PMID- 21862494
TI  - Human cerebral microcirculation and oxygen saturation during propofol-induced
      reduction of bispectral index.
AB  - BACKGROUND: Propofol reduces cerebral blood flow (CBF) secondary to cerebral
      metabolic depression. However, in vitro and in vivo studies demonstrate that
      propofol directly dilates the vascular smooth muscle. This study investigates the
      effects of propofol-induced changes in bispectral index (BIS) on cerebral
      microcirculation and oxygenation during craniotomies. METHODS: In 21 craniotomy
      patients undergoing routine craniotomy, anaesthesia was maintained with propofol
      4-10 mg kg-1 h-1 and remifentanil 0.1-0.4 ug kg-1 min-1. Propofol concentration
      was adjusted to achieve higher BIS (target 40) or lower BIS (target 20). Regional
      measurements of capillary venous blood flow (rvCBF), oxygen saturation (srvO2),
      and haemoglobin amount (rvHb) at 2 mm (grey matter) and 8 mm (white matter)
      cerebral depth were randomly performed at higher and lower BIS by combined laser
      Doppler flowmetry and spectroscopy. Calculations: approximated arteriovenous
      difference in oxygen content (avDO2) and cerebral metabolic rate of oxygen
      (aCMRO2). RESULTS: mean values (sd). STATISTICS: Mann-Whitney test (*P<0.05).
      Results Human cerebral microcirculation and oxygen saturation were assessed at
      propofol dosages 5.1 (2.3) mg kg-1 h-1 [BIS 40 (9)] and 7.8 (2.1) mg kg-1 h-1
      [BIS 21 (7)]. Propofol-induced reduction in BIS resulted in increased srvO2
      (P=0.018), and decreased avDO2 (P=0.025) and aCMRO(2) (P=0.022), in 2 mm cerebral
      depth, while rvCBF and rvHb remained unchanged. In 8 mm cerebral depth, srvO2,
      rvCBF, rvHb, and also calculated parameters avDO2 and aCMRO2 remained unaltered.
      CONCLUSIONS: Findings suggest alteration of the CBF/CMRO2 ratio by propofol in
      cortical brain regions; therefore, it might be possible that propofol affects
      coupling of flow and metabolism in the cerebral microcirculation.

PMID- 21862495
TI  - Effects of increasing sevoflurane MAC levels on mid-latency auditory evoked
      potentials in infants, schoolchildren, and the elderly.
AB  - BACKGROUND: Detection of mid-latency auditory evoked potentials (MLAEPs) is a
      technology to monitor central nervous structures. As seen in adults and children,
      general anaesthesia influences the MLAEP latencies. MLAEP detection seems to be a
      promising tool to assess different levels of anaesthesia depth in adults and
      children. METHODS: MLAEPs were recorded in 10 infants (2 months-3 yr), 12
      schoolchildren (6-14 yr), and 10 elderly (75-89 yr) under general anaesthesia
      with increasing concentrations of sevoflurane at steady state. In addition,
      MLAEPs were detected before and after the application of sufentanil. RESULTS: At
      all different ages, MLAEP latencies increased significantly with higher volume
      percentages of sevoflurane. These results were also detectable when MAC values of
      sevoflurane were compared with MLAEP peaks. An age-dependent effect could be
      displayed as elderly people need lower absolute sevoflurane concentrations to
      achieve the same MLAEP peak increase. Overall, the application of sufentanil
      under steady-state sevoflurane application at 1 MAC did not importantly affect
      the MLAEP latencies. CONCLUSIONS: MLAEP latencies increase at the influence of
      sevoflurane in a dose-dependent manner and in relation to age. These results
      imply that MLAEP detection is a reasonable tool for monitoring hypnotic effects
      at all ages. Further studies are required to standardize MLAEP alterations
      related to effects of medication used for general anaesthesia at all different
      ages.

PMID- 21862496
TI  - Responsiveness of the frontal EMG for monitoring the sedation state of critically
      ill patients.
AB  - BACKGROUND: Excessive sedation is associated with adverse patient outcomes during
      critical illness, and a validated monitoring technology could improve care. We
      developed a novel method, the responsiveness index (RI) of the frontal EMG. We
      compared RI data with Ramsay clinical sedation assessments in general and cardiac
      intensive care unit (ICU) patients. METHODS: We developed the algorithm by
      iterative analysis of detailed observational data in 30 medical-surgical ICU
      patients and described its performance in this cohort and 15 patients recovering
      from scheduled cardiac surgery. Continuous EMG data were collected via frontal
      electrodes and RI data compared with modified Ramsay sedation state assessments
      recorded regularly by a blinded trained observer. RI performance was compared
      with EntropyTM across Ramsay categories to assess validity. RESULTS: RI
      correlated well with the Ramsay category, especially for the cardiac surgery
      cohort (general ICU patients rho=0.55; cardiac surgery patients rho=0.85, both
      P<0.0001). Discrimination across all Ramsay categories was reasonable in the
      general ICU patient cohort [P(K)=0.74 (sem 0.02)] and excellent in the cardiac
      surgery cohort [P(K)=0.92 (0.02)]. Discrimination between 'lighter' vs 'deeper'
      (Ramsay 1-3 vs 4-6) was good for general ICU patients [P(K)=0.80 (0.02)] and
      excellent for cardiac surgery patients [P(K)=0.96 (0.02)]. Performance was
      significantly better than EntropyTM. Examination of individual cases suggested
      good face validity. CONCLUSIONS: RI of the frontal EMG has promise as a
      continuous sedation state monitor in critically ill patients. Further
      investigation to determine its utility in ICU decision-making is warranted.

PMID- 21862497
TI  - Prediction of arterial oxygen partial pressure after changes in FIO2: validation
      and clinical application of a novel formula.
AB  - BACKGROUND: Existing methods allow prediction of Pa(O2) during adjustment of
      Fi(O2). However, these are cumbersome and lack sufficient accuracy for use in the
      clinical setting. The present studies aim to extend the validity of a novel
      formula designed to predict Pa(O2) during adjustment of Fi(O2) and to compare it
      with the current methods. METHODS: Sixty-seven new data sets were collected from
      46 randomly selected, mechanically ventilated patients. Each data set consisted
      of two subsets (before and 20 min after Fi(O2) adjustment) and contained
      ventilator settings, pH, and arterial blood gas values. We compared the accuracy
      of Pa(O2) prediction using a new formula (which utilizes only the pre-adjustment
      Pa(O2) and pre- and post-adjustment Fi(O2) with prediction using assumptions of
      constant Pa(O2)/Fi(O2) or constant Pa(O2)/Pa(O2). Subsequently, 20 clinicians
      predicted Pa(O2) using the new formula and using Nunn's isoshunt diagram. The
      accuracy of the clinician's predictions was examined. RESULTS: The 95% limits of
      agreement (LA(95%)) between predicted and measured Pa(O2) in the patient group
      were: new formula 0.11 (2.0) kPa, Pa(O2)/Fi(O2) -1.9 (4.4) kPa, and Pa(O2)/Pa(O2)
      -1.0 (3.6) kPa. The LA(95%) of clinicians' predictions of Pa(O2) were 0.56 (3.6)
      kPa (new formula) and -2.7 (6.4) kPa (isoshunt diagram). CONCLUSIONS: The new
      formula's prediction of changes in Pa(O2) is acceptably accurate and reliable and
      better than any other existing method. Its use by clinicians appears to improve
      accuracy over the most popular existing method. The simplicity of the new method
      may allow its regular use in the critical care setting.

PMID- 21862498
TI  - Mechanisms involved in the desflurane-induced post-conditioning of isolated human
      right atria from patients with type 2 diabetes.
AB  - BACKGROUND: Desflurane triggers post-conditioning in the diabetic human
      myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine
      triphosphate-sensitive potassium (mitoK(ATP)) channels, Akt, and glycogen
      synthase kinase-3beta (GSK-3beta) were involved in the in vitro desflurane
      induced post-conditioning of human myocardium from patients with type 2 diabetes.
      METHODS: The isometric force of contraction (FoC) of human right atrial
      trabeculae obtained from patients with type 2 diabetes was recorded during 30 min
      of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered
      during the first 5 min of reoxygenation either alone or in the presence of
      calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK(ATP) channel
      antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a
      mitoK(ATP) channel opener) were superfused during early reoxygenation. The FoC at
      the end of the 60 min reoxygenation period was compared among treatment groups
      (FoC(60); mean and sd). The phosphorylation of Akt and GSK-3beta was studied
      using western blotting. RESULTS: Desflurane enhanced the recovery of force
      [FoC(60): 79 (3)% of baseline] after 60 min of reoxygenation when compared with
      the control group (P>0.0001). Calphostin C and 5-HD abolished the beneficial
      effect of desflurane-induced post-conditioning (both P<0.0001). Phorbol 12
      myristate 13-acetate and diazoxide enhanced the FoC(60) when compared with the
      control group (both P<0.0001). Desflurane increased the level of phosphorylation
      of Akt and GSK-3beta (P<0.0001). CONCLUSIONS: Desflurane-induced post
      conditioning in human myocardium from patients with type 2 diabetes was mediated
      by the activation of PKC, the opening of the mitoK(ATP) channels, and the
      phosphorylation of Akt and GSK-3beta.

PMID- 21862499
TI  - A qualitative approach to Bayes' theorem.
AB  - While decisions made according to Bayes' theorem are the academic normative
      standard, the theorem is rarely used explicitly in clinical practice. Yet the
      principles can be followed without intimidating mathematics. To do so, one can
      first categorise the prior-probability of the disease being tested for as very
      unlikely (less likely than 10%), unlikely (10-33%), uncertain (34-66%), likely
      (67-90%) or very likely (more likely than 90%). Usually, for disorders that are
      very unlikely or very likely, no further testing is needed. If the prior
      probability is unlikely, uncertain or likely, a test and a Bayesian-inspired
      update process incorporating the result can help. A positive result of a good
      test increases the probability of the disorder by one likelihood category (eg,
      from uncertain to likely) and a negative test decreases the probability by one
      category. If testing is needed to escape the extremes of likelihood (eg, a very
      unlikely but particularly dangerous condition or in the circumstance of
      population screening, or a very likely condition with a particularly noxious
      treatment), two tests may be needed to achieve. Negative results of tests with
      sensitivity >=99% are sufficient to rule-out a diagnosis; positive results of
      tests with specificity >=99% are sufficient to rule-in a diagnosis. This method
      overcomes some common heuristic errors: ignoring the base rate, probability
      adjustment errors and order effects. The simplicity of the method, while still
      adhering to the basic principles of Bayes' theorem, has the potential to increase
      its application in clinical practice.

PMID- 21862500
TI  - Modifiable risk factors for stillbirth in high-income countries include
      overweight and obesity, maternal age and smoking.

PMID- 21862501
TI  - Multidisciplinary care for Parkinson's disease: not if, but how!

PMID- 21862502
TI  - Republished review: cataract and cognitive impairment: a review of the
      literature.
AB  - Acquired cataract and cognitive impairment are both common age-related problems,
      and ophthalmologists are increasingly likely to encounter patients who have both.
      Patients with dementia types who display early visuoperceptual impairment may
      present first to ophthalmology services. When these patients have coexisting
      cataract, it may be difficult to distinguish visual complaints due to cataract
      from those due to dementia. The interaction between visual impairment due to
      cataract and neurodegenerative disorders affecting the central visual pathways,
      is not fully understood. Visual impairment due to cataract may stress impaired
      attentional mechanisms and cataract extraction may improve cognitive performance
      in some patients with early cognitive impairment; however, the benefits of
      cataract surgery in established dementia are less clear. In this study, the
      literature on this subject was reviewed and the implications for practice were
      considered.

PMID- 21862503
TI  - Republished review: systematic review and meta-analysis of psychomotor effects of
      mobile phone electromagnetic fields.
AB  - OBJECTIVES Over the past 10 years there has been increasing concern about the
      possible behavioural effects of mobile phone use. This systematic review and meta
      analysis focuses on studies published since 1999 on the human cognitive and
      performance effects of mobile phone-related electromagnetic fields (EMF). METHODS
      PubMed, Biomed, Medline, Biological Sciences, PsychInfo, PsycARTICLES,
      Environmental Sciences and Pollution Management, Neurosciences Abstracts and Web
      of Science professional databases were searched and 24 studies selected for meta
      analysis. Each study had to have at least one psychomotor measurement result as a
      main outcome. Data were analysed using standardised mean difference (SMD) as the
      effect size measure. RESULTS Only three tasks (2-back, 3-back and simple reaction
      time (SRT)) displayed significant heterogeneity, but after studies with extreme
      SMD were excluded using sensitivity analysis, the statistical significance
      disappeared (chi(2)(7)=1.63, p=0.20; chi(2)(6)=1.00, p=0.32; chi(2)(10)=14.04,
      p=0.17, respectively). Following sensitivity analysis, the effect of sponsorship
      and publication bias were assessed. Meta-regression indicated a significant
      effect (b1/40.12, p<0.05) only for the 2-back task with mixed funding (industry
      and public/charity). Funnel plot inspection revealed a significant publication
      bias only for two cognitive tasks: SRT (Begg's rank correlation r=0.443; Egger's
      test b=-0.652) and the subtraction task (Egger's test b=-0.687). CONCLUSIONS
      Mobile phone-like EMF do not seem to induce cognitive and psychomotor effects.
      Nonetheless, the existence of sponsorship and publication biases should encourage
      WHO intervention to develop official research standards and guidelines. In
      addition, future research should address critical and neglected issues such as
      investigation of repeated, intensive and chronic exposures, especially in highly
      sensitive populations such as children.

PMID- 21862504
TI  - A twilight adventure.

PMID- 21862505
TI  - Bone scan can be spared in asymptomatic prostate cancer patients with PSA of <=20
      ng/ml and Gleason score of <=6 at the initial stage of diagnosis.
AB  - OBJECTIVE: According to several guidelines, it is acceptable to spare a bone scan
      in the patients who are newly diagnosed with low-risk prostate cancer. Our aim is
      to clarify a suitable group whereby a bone scan could be spared at the initial
      staging of prostate cancer. METHODS: Consecutive 857 patients who were newly
      diagnosed from 2004 through 2009 and received bone scans using technetium 99m
      methylene diphosphonate at the initial staging were enrolled. The proportion of
      positive bone metastases by age distribution, prostate-specific antigen level at
      diagnosis, Gleason score and clinical T stage were evaluated. Univariate and
      multivariate logistic regression analyses were performed to identify the
      predictors of positive bone metastases. RESULTS: Of all 857 patients, 40 patients
      (4.7%) showed bone metastases. Patients with higher age, prostate-specific
      antigen level, clinical stage and Gleason score showed significantly higher rate
      of bone metastases (P < 0.001). In univariate logistic regression analyses, age,
      prostate-specific antigen level, clinical stage and Gleason score were
      independent predictors of bone metastasis. The multivariate analysis showed that
      both the prostate-specific antigen level >50 ng/ml and the Gleason score >=4 + 3
      were independent predictors of bone metastases. CONCLUSIONS: The incidences of
      bone metastases in patients with a prostate-specific antigen level of <=20 ng/ml
      and Gleason score of <=6 were reasonably low. Collectively, a bone scan is not
      necessary as a routine examination for these patients at their initial staging of
      prostate cancer.

PMID- 21862506
TI  - Promising long-term results with attenuated adverse effects by methotrexate
      containing sequential chemoradiation therapy in locally advanced head and neck
      squamous cell carcinoma.
AB  - OBJECTIVE: To reduce severe acute and late toxicities without compromising organ
      preservation survival in patients with locoregionally advanced head and neck
      squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin
      fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation.
      METHODS: Two induction courses of methotrexate (40 mg/m(2)/day, days 1, 8 and
      15), cisplatin and 5-fluorouracil (25 and 750 mg/m(2)/day, days 1-4) were given
      in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head
      and neck squamous cell carcinoma. Responders received concurrent chemoradiation
      with weekly cisplatin (20 mg/m(2)/day) and 5-fluorouracil (400 mg/m(2)/day) on
      day 1. RESULTS: Among 57 patients (58% with Stage IV and hypopharyngeal cancer),
      the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT,
      respectively. A total of 49 patients completed induction and began concurrent
      chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up
      of 62 months (range 19-83 months) for the current survivors, the 3-year overall
      and disease-specific survival estimates were 50 and 58%, respectively. The 3-year
      organ preservation survival was 74% in patients who achieved complete remission
      after concurrent chemoradiation, and 96% of current survivors are tracheotomy and
      feeding tube-free. No patient without local/regional failure suffered from
      distant metastasis. CONCLUSIONS: Methotrexate-cisplatin-fluorouracil induction
      chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation
      is an acute and late toxicity-acceptable protocol without attenuating organ
      preservation survival in patients with locoregionally advanced head and neck
      squamous cell carcinoma. In this patient cohort with advanced head and neck
      squamous cell carcinoma, overall and organ preservation survivals were
      encouraging, and provided promising long-term benefits of this approach.

PMID- 21862507
TI  - Experimental simulation of personal dosimetry in production of medical
      radioisotopes by research reactor.
AB  - Due to their work conditions, research reactor personnel are exposed to ionising
      nuclear radiations. Because the absorbed dose values are different for different
      tissues due to variations in sensitivity, in this work personal dosimetry has
      been performed under normal working conditions at anatomical locations relevant
      to more sensitive tissues as well as for the whole body by employing a Rando
      phantom and thermoluminescent dosemeters (TLDs). Fifty-two TLDs-100H were
      positioned at high-risk organ locations such as the thyroid, eyes as well as the
      left breast, which was used to assess the whole-body dose in order to study the
      absorbed doses originating from selected locations in the vicinity of the
      reactor. The results have employed the tissue weighting factors based on
      International Commission on Radiological Protection ICRP 103 and ICRP 60 and the
      measured results were below the dose limits recommended by ICRP. The mean
      effective dose rates calculated from ICRP 103 were the following: whole body,
      30.64-6.44 uSv h(-1); thyroid, 1.22-0.23 uSv h(-1); prostate, 0.085-0.045 uSv h(
      1); gonads, 1.00-0.51 uSv h(-1); breast, 3.68-0.77 uSv h(-1); and eyes, 33.74
      7.01 uSv h(-1).

PMID- 21862508
TI  - Coverage of gingival recession defects using acellular dermal matrix allograft
      with or without beta-tricalcium phosphate.
AB  - The aim of this study was to investigate the effect of beta-tricalcium phosphate
      (beta-TCP) particles in combination with acellular dermal matrix (ADM) allograft
      in gingival recession. Experimental gingival recession defects were created in
      beagle dogs and randomly assigned to one of the following groups: ADM, ADM + beta
      TCP, or coronally positioned flap (CPF; control). Tissues were histologically
      examined at 4, 8, or 16 weeks following treatment. A greater thickness of gingiva
      was observed at the sites treated in both the ADM + beta-TCP and ADM groups than
      in the CPF group. The ADM + beta-TCP group showed a statistically significant
      increase in both new bone and cementum formations compared to the ADM group. The
      results suggest that the combination of beta-TCP and ADM is more effective in
      promoting new bone and cementum formations than ADM graft alone.

PMID- 21862509
TI  - Effect of beta-tricalcium phosphate coated with zoledronic acid on human
      osteoblasts and human osteoclasts in vitro.
AB  - The combination of a bone graft material with bisphosphonates (BPs) might be
      advantageous for an optimal balance of material resorption and stimulation of
      bone formation. This study investigated the effect of beta-tricalcium phosphate
      (beta-TCP) bone grafts coated with zoledronic acid (ZOL) on osteoblast-like cells
      and osteoclast-like cells (OLC). As a drug carrier, the polymer poly(D,L-lactide)
      was used and three different concentrations of ZOL were tested. beta-TCP coated
      with ZOL stimulated the production of osteocalcin (OC), osteoprotegerin, and
      sRANKL in osteoblast-like cells. The polymer coating alone caused a significant
      increase in collagen type 1 and OC production. OLC viability was inhibited and
      the tartrate-resistant acidic phosphatase isoform-5b was significantly decreased
      after cultivation on polymer-coated beta-TCP for 12 days. The three different
      concentrations of ZOL decreased cell viability and no TRAPiso-5b was detectable,
      indicating a strong reduction of the TRAPiso-5b after 12 days in culture. After
      21 days in culture, only the higher ZOL concentrations significantly reduced cell
      viability and TRAPiso-5b. The results of this study show that coating of beta-TCP
      with ZOL has stimulating effects on osteoblast-like cells. Additionally, an
      inhibition of osteoclasts was seen. The combination of this bone grafting
      material with BPs might, therefore, be effective in the treatment of large bone
      defects.

PMID- 21862510
TI  - The adhesion and proliferation of bone marrow-derived mesenchymal stem cells
      promoted by nanoparticle surface.
AB  - This study's aim consists of evaluating the adhesion and proliferation of
      mesenchymal stem cells (MSCs) derived from rat bone marrow on nanoparticle
      Titanium (Ti) surface. Hence, passage 3 MSCs were, respectively, seeded on
      nanoparticle Ti and pure Ti surfaces and then cultured for 32 h. Cell morphology
      and viability were separately examined by scanning electron microscopy and 3-(4,5
      dimethylthiazsol-2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover, the
      mitotic rate of the attached MSCs was observed through immunocytochemistry. The
      real-time polymerase chain reaction was applied to determine the adhesion
      associated messenger ribonucleic acid (mRNA), CD44 gene encoding variant isoform
      6 (CD44 V6), and the integrinbeta1 level. The results showed that MSCs performed
      better in faster extension on the nanoparticle Ti surface than on the pure Ti
      surface after culturing for 4 h, and were quicker in fusion patterns after 16 h.
      Furthermore, cell viability was significantly increased on the nanoparticle Ti
      surface compared to that of the pure Ti surface 16 h after initial seeding (p <
      0.05), and the mitotic rate of attached MSCs on the nanoparticle Ti surface was
      higher than that on the pure Ti surface after 32 h (p < 0.05). More
      interestingly, the CD44 V6 and integrinbeta1 mRNA in the nanoparticle Ti surface
      group expressed higher than that in the pure Ti surface group after 4 h (p <
      0.05), and positive correlation between CD44 V6 and integrinbeta1 was found
      through statistical analysis (correlation coefficient r (s) = 0.98, p < 0.05).
      Our study's result indicates that a nanoparticle Ti surface can significantly
      promote the adhesion and proliferation of MSCs, and also improve the bioactivity
      of Ti surface.

PMID- 21862511
TI  - Macroporous bioceramics: a remarkable material for bone regeneration.
AB  - This review summarises the major developments of macroporous bioceramics used
      mainly for repairing bone defects. Porous bioceramics have been receiving
      attention ever since their larger surface area was reported to be beneficial for
      the formation of more rigid bonds with host tissues. The study of porous
      bioceramics is important to overcome the less favourable bonds formed between
      dense bioceramics and host tissues, especially in healing bone defects.
      Macroporous bioceramics, which have been studied extensively, include
      hydroxyapatite, tricalcium phosphate, alumina, and zirconia. The pore size and
      interconnections both have significant effects on the growth rate of bone
      tissues. The optimum pore size of hydroxyapatite scaffolds for bone growth was
      found to be 300 um. The existence of interconnections between pores is critical
      during the initial stage of tissue ingrowth on porous hydroxyapatite scaffolds.
      Furthermore, pore formation on beta-tricalcium phosphate scaffolds also allowed
      the impregnation of growth factors and cells to improve bone tissues growth
      significantly. The formation of vascularised tissues was observed on macroporous
      alumina but did not take place in the case of dense alumina due to its bioinert
      nature. A macroporous alumina coating on scaffolds was able to improve the
      overall mechanical properties, and it enabled the impregnation of bioactive
      materials that could increase the bone growth rate. Despite the bioinertness of
      zirconia, porous zirconia was useful in designing scaffolds with superior
      mechanical properties after being coated with bioactive materials. The pores in
      zirconia were believed to improve the bone growth on the coated system. In
      summary, although the formation of pores in bioceramics may adversely affect
      mechanical properties, the advantages provided by the pores are crucial in
      repairing bone defects.

PMID- 21862512
TI  - Effect of fluorine addition on the biological performance of hydroxyapatite
      coatings on Ti by aerosol deposition.
AB  - Dense and well-adherent fluoridated hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2-x )F(
      x ), FHA] coatings with various amounts of fluorine contents (x = 0, 0.5, 1.0,
      1.5, and 2.0) were deposited on commercially available pure titanium by aerosol
      deposition using FHA powders in order to investigate the effect of fluorine
      content on the properties of the coatings. FHA powders with different
      compositions were synthesized by solid-state reactions of hydroxyapatite (HA) and
      fluorapatite (FA) powders at various ratios. X-ray diffraction and Fourier
      transform infrared spectroscopy results showed that fluoride ions were
      successfully incorporated into the HA lattice for both the FHA powders and the
      FHA coatings. Scanning electron microscopy analysis revealed dense
      microstructures and good substrate adhesion of the coatings with high adhesion
      strengths of more than 33.1 MPa. The dissolution behavior in a tris-buffered
      saline solution indicated that the dissolution rate of the FHA coatings decreased
      as a result of increasing the fluorine content in the coatings. In addition, in
      vitro cellular tests, including cell attachment, proliferation, and alkaline
      phosphatase activity of MC3T3-E1 preosteoblast cells grown on the coatings,
      demonstrated that an FHA coating with a moderate degree of F(-) substitution, x =
      1.0, had a stronger stimulating effect on cell proliferation and differentiation.
      These results suggested that there exists an optimum fluorine content level in
      the FHA coatings for the best long-term stability and cellular responses.

PMID- 21862513
TI  - Biocompatible, smooth, plasma-treated nickel-titanium surface--an adequate
      platform for cell growth.
AB  - High nickel content is believed to reduce the number of biomedical applications
      of nickel-titanium alloy due to the reported toxicity of nickel. The reduction in
      nickel release and minimized exposure of the cell to nickel can optimize the
      biocompatibility of the alloy and increase its use in the application where its
      shape memory effects and pseudoelasticity are particularly useful, e.g., spinal
      implants. Many treatments have been tried to improve the biocompatibility of Ni
      Ti, and results suggest that a native, smooth surface could provide sufficient
      tolerance, biologically. We hypothesized that the native surface of nickel
      titanium supports cell differentiation and insures good biocompatibility. Three
      types of surface modifications were investigated: thermal oxidation, alkali
      treatment, and plasma sputtering, and compared with smooth, ground surface.
      Thermal oxidation caused a drop in surface nickel content, while negligible
      chemistry changes were observed for plasma-modified samples when compared with
      control ground samples. In contrast, alkali treatment caused significant increase
      in surface nickel concentration and accelerated nickel release. Nickel release
      was also accelerated in thermally oxidized samples at 600  degrees C, while in
      other samples it remained at low level. Both thermal oxidation and alkali
      treatment increased the roughness of the surface, but mean roughness R(a) was
      significantly greater for the alkali-treated ones. Ground and plasma-modified
      samples had 'smooth' surfaces with R(a)=4 nm. Deformability tests showed that the
      adhesion of the surface layers on samples oxidized at 600  degrees C and alkali
      treatment samples was not sufficient; the layer delaminated upon deformation. It
      was observed that the cell cytoskeletons on the samples with a high nickel
      content or release were less developed, suggesting some negative effects of
      nickel on cell growth. These effects were observed primarily during initial cell
      contact with the surface. The most favorable cell responses were observed for
      ground and plasma-sputtered surfaces. These studies indicated that smooth, plasma
      modified surfaces provide sufficient properties for cells to grow.

PMID- 21862514
TI  - Effects of dexamethasone-loaded PLGA microspheres on human fetal osteoblasts.
AB  - Integration of a drug delivery function into implantable medical devices enables
      local release of specific bioactives to control cells-surface interactions. One
      alternative to achieve this biofunctionality for bone implants is to incorporate
      particulate drug delivery systems (DDSs) into the rough or porous implant
      surfaces. The scope of this study was to assess the effects of a model DDS
      consisting of poly(D,L-lactide-co-glycolide) (PLGA) microspheres loaded with an
      anti-inflammatory drug, dexamethasone (DXM), on the response of Simian Virus
      immortalized Human Fetal Osteoblast (SV-HFO) cells. The microspheres were
      prepared by the oil-in-water emulsion/solvent evaporation method, whereas cells
      response was investigated by Alamar Blue test for viability, alkaline phosphatase
      (ALP) activity for differentiation, and Alizarin Red staining for matrix
      mineralization. Cell viability was not affected by the presence of increased
      concentrations of polymeric microspheres in the culture media. Furthermore, in
      the cultures with DXM-loaded microspheres, ALP activity was expressed at levels
      similar with those obtained under osteogenic conditions, indicating that DXM
      released from the microsphere-stimulated cell differentiation. Matrix
      mineralization occurred preferentially around the DXM-loaded microspheres
      confirming that the released DXM could act as osteogenic supplement for the
      cells. These in vitro findings suggest that a particulate PLGA-DXM DDS may
      actually provide dual, anti-inflammatory and osteogenic functions when
      incorporated on the surface of bone implants.

PMID- 21862515
TI  - Enhancing biocompatibility and corrosion resistance of Mg implants via surface
      treatments.
AB  - Oxide coating layers were formed on a pure magnesium (Mg) substrate through
      anodization and micro-arc oxidation (MAO) in order to enhance the
      biocompatibility and reduce the degradation rate. A thin, smooth MgO coating
      layer was formed after the anodization. On the other hand, when the Mg was
      treated using the MAO process, a relatively thick, rough MgO layer was formed.
      The corrosion properties were investigated using electrochemical and ion release
      tests in a simulated body fluid. Both the anodization and the MAO treatment
      enhanced the corrosion resistance of the Mg specimens. However, the MgO layers
      that formed on the surface were not stable enough to render favorable
      environments for cell growth. The anodized and MAO-treated specimens were post
      treated in a cell-culturing medium in order to improve the stability of the
      coating layer. The biocompatibility was evaluated using in vitro cell tests,
      including cell attachment, DNA measurement, and alkaline phosphatase (ALP)
      activity tests. The DNA levels of the surface-treated Mg were about 6-10 times
      higher than the bare Mg. The ALP activity levels were also more than double after
      either the anodization or the MAO followed by the post-treatments. These results
      demonstrated that the biocompatibility and the corrosion resistance of Mg were
      significantly improved by the series of surface treatments.

PMID- 21862516
TI  - Identification of alternative splicing events regulated by an Arabidopsis
      serine/arginine-like protein, atSR45a, in response to high-light stress using a
      tiling array.
AB  - We have demonstrated that an Arabidopsis serine/arginine rich-like protein,
      atSR45a, interacts with other splicing factors and its expression is markedly
      induced by high-light stress, suggesting the involvement of atSR45a in the
      regulation of stress-responsive alternative splicing. A whole-genome tiling array
      identified the alternative splicing of genes regulated by atSR45a by comparing
      gene expression profiles in wild-type and knockout atSR45a (KO-sr45a) plants
      under high-light stress. The expression levels of genomic regions within 217
      genes were significantly altered in the KO-sr45a plants compared with the wild
      type plants. Many genes encoded factors involved in signal transduction, cell
      cycle and DNA processing, protein fate and transcription. A semi-quantitative
      reverse transcription-PCR (RT-PCR) analysis confirmed changes in the transcript
      levels and/or alternative splicing efficiency under high-light stress in 18
      genes, suggesting that atSR45a affects directly or indirectly not only
      alternative splicing efficiency but also the transcription of these target genes.
      Changes in the expression of atSR45a in response to high-light stress temporally
      correlated with changes in the alternative splicing efficiency and transcript
      levels of three and one target genes, respectively. Sequencing of the
      alternatively spliced variants of three target genes showed that atSR45a
      suppresses the splicing efficiency of intron retention-type alternative splicing
      events. These findings indicated the importance of atSR45a to the diversification
      of the transcriptome under high-light stress.

PMID- 21862517
TI  - Is the improvement of prognosis of patients with metastatic pulmonary
      adenocarcinoma treated with TCM herbal medicine due to lag time to treatment
      bias?
AB  - BACKGROUND. Traditional Chinese herbal medicine was associated with improved
      prognosis in patients with performance score 0-1 at the time of diagnosis of
      stage IV pulmonary adenocarcinoma (PAC) treated with platinum-based chemotherapy
      (PBT). OBJECTIVE. The authors investigated the effect of 1- to 4-month lag time
      to traditional Chinese medicine (TCM) treatment on the median and 1-year survival
      of PBT-PAC patients. METHODS: The median lag time to treatment was 3 months. In
      the first 3 months, about 35% of the patients died, but thereafter the survival
      curve flattened off and the death of the next 35% to 40% of patients took 9
      months. Leaving out patients with lag time up to 3 months therefore would be a
      reasonable choice. To be on the safe side, the effects of leaving out patients up
      to 4 months were investigated. The Kaplan-Meier survival curves were used.
      RESULTS: The median and 1-year survival of the PBT-PAC patients was 5.0 months
      and 27%, respectively. Leaving out patients with 0-1 month follow-up, 0-2, 0-3,
      and 0-4 months follow-up changed the median and 1-year survival, respectively, to
      5.5 months and 32%, 6.5 months and 36%, 9.0 months and 43%, and 10.0 months and
      52%. The median survival of PBT + TCM in PAC patients was 22.6 months and 78%.
      Median lag time to TCM treatment was 3.0 months. With up to 4 months lag time to
      treatment due to combined patients' and TCM doctor's waiting time, the improved
      survival of PBT + TCM performance score 0-1 (fully ambulant) patients at the time
      of diagnosis still is significant (P < .01, hazard ratio = 0.51). Moreover, the
      survival of patients treated by TCM doctors with little or more months lag time
      to treatment was not different (P = .79). CONCLUSION: Increasing lag time to
      treatment up to 4 months improves the median and 1-year survival of PBT patients
      without TCM but is unlikely to explain the greatly improved prognosis of PBT +
      TCM treated patients with fully ambulant stage IV PAC.

PMID- 21862518
TI  - Alteration of hypothalamic-pituitary-thyroid axis function in non-small-cell lung
      cancer patients.
AB  - The aim of this study was to evaluate the hypothalamic-pituitary-thyroid (HPT)
      axis function in patients suffering from lung cancer. Thyrotropin-releasing
      hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4),
      interleukin (IL)-2, and melatonin serum levels were measured in blood samples
      collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53
      years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63
      years). Relationships between hormone levels overall and over time of day were
      evaluated within and among groups. A prominent circadian rhythm with peaks near
      midnight was present for TSH and melatonin serum levels in both H and C,
      indicating similar synchronization of the main body clock to the 24-hour
      environmental light-dark cycle. As regards 24-hour means in H and C, TSH was
      lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in
      melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive
      correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a
      negative correlation in both groups. For FT4 versus IL-2, a negative correlation
      was found in C but not for H, whereas TSH versus TRH showed no correlation for
      either group. Both groups were found to be similarly synchronized to the 24-hour
      sleep-wake schedule, but HPT axis function was altered in patients suffering from
      lung cancer. When compared with healthy controls, cancer patients showed
      modifications of hormone serum levels overall and a negative correlation between
      individual TRH and FT4 levels.

PMID- 21862519
TI  - Amelioration of chemical-induced skin carcinogenesis by Aegle marmelos, an Indian
      medicinal plant, fruit extract.
AB  - Chemoprevention is a novel approach to study the anti-initiating and anti-tumor
      promoting efficacy of medicinal plants and their active principles. The present
      study investigated the chemopreventive potential of Aegle marmelos fruit extract
      in 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis and its influence
      on oxidative stress and the antioxidant defense system. The oral administration
      of A marmelos at 100 mg/kg body weight/day during peri-initiational,
      postinitiational, and peri- & postinitiational phases of papillomagenesis showed
      significant reduction in tumor incidence, tumor yield, tumor burden, and
      cumulative number of papillomas when compared with carcinogen-treated control.
      The average latent period significantly increased (7.88 weeks; control group) to
      9.45, 11.11, and 11.54 weeks in different A marmelos extract (AME) experimental
      groups. Enzyme analysis of skin and liver showed a significant elevation in
      antioxidant parameters such as superoxide dismutase, catalase, glutathione, and
      vitamin C in AME-treated groups when compared with the carcinogen-treated
      control. The elevated level of lipid peroxidation in the positive control was
      significantly inhibited by AME administration. These results indicate that AME
      has the potential to reduce chemical-induced skin papillomas by enhancing the
      antioxidant defense system.

PMID- 21862520
TI  - Retrograde transpopliteal approach of iliofemoral lesions.
AB  - PURPOSE: Aim of this study is to present our initial experience with the use of
      the retrograde popliteal artery access in patients with certain anatomic lesions.
      METHODS: Between September 2008 and September 2010, 24 patients underwent a
      transpopliteal retrograde subintimal recanalization. Instead of its usage when
      antegrade recanalization failed, the "facedown" technique was preferred as a
      first choice in patients with common femoral artery stenosis or occlusion,
      proximal lesions of the superficial femoral artery (SFA) with no stump, severe
      obesity, tandem iliac, and SFA lesions. RESULTS: Technical success was achieved
      in 91.7% of patients.The complication rate was 12.5%. The primary patency at 6,
      12, and 18 months was 86.4%, 65.8%, and 65.8%, respectively. CONCLUSIONS: The
      retrograde popliteal artery approach can be considered as the primary SFA
      recanalization strategy in carefully selected patients, with competitive
      immediate and midterm results.

PMID- 21862521
TI  - Thyroid autoimmunity in children with coeliac disease: a prospective survey.
AB  - BACKGROUND: Thyroid autoimmunity (TA) is often associated with coeliac disease
      (CD). OBJECTIVE: To evaluate, in children and adolescents with CD on a gluten
      free diet (GFD): (1) the prevalence of TA; (2) the impact of TA on growth and the
      need for L-thyroxine (L-T4) treatment, during a longitudinal survey. METHOD:
      Between January and December 2005, 545 patients with CD, prospectively followed
      up until December 2007, and 622 controls were screened for TA.
      Antithyroperoxidase and antithyroglobulin antibodies were assayed and, if
      positive, serum free tri-iodothyronine, free thyroxine and thyroid-stimulating
      hormone (TSH) assays and thyroid ultrasound were performed. L-T4 was started if
      TSH was >5.5 mU/ml at two successive measurements. RESULTS: There was no
      significant difference in TA prevalence between patients with CD on a GFD (10%)
      and controls (8.2%). Duration of GFD differed significantly in coeliac patients
      with TA in comparison with those without TA (7.9+/-0.9 and 10.2+/-0.3 years,
      p<0.001), but no significant difference was found for weight and height gain
      (1.8+/-1.0 vs 3.7+/-1.5 and 2.1+/-1.2 kg/year vs 4.0+/-1.1 cm/year,
      respectively). At the end of the follow-up an increase of 7% in the prevalence of
      patients with CD with TA requiring L-T4 was found. CONCLUSIONS: TA seems no more
      common in paediatric and adolescent patients with CD on a GFD than in controls;
      its clinical evolution does not seem to impact on growth. Therefore, a long-term
      regular screening programme for thyroid disease may not be necessary for all
      patients with CD on a GFD, but only for those who are suspected of having thyroid
      diseases.

PMID- 21862522
TI  - 'Turning the Tide': increasing and strengthening child health research.

PMID- 21862523
TI  - Community solutions for the community's problem: an evaluation of three New
      Zealand community-based treatment programs for child sexual offenders.
AB  - The recidivism rate of 203 people mandated by the courts to attend three
      community-based child sexual offender treatment programs (175 treatment cases and
      28 assessment-only cases) was assessed and compared with a probation comparison
      group. The recidivism rate was 8.1% for all participants treated in the community
      based programs and 5.2% for participants who completed treatment. The recidivism
      rate for program attendees was approximately half that of those in the probation
      comparison group. The drop-out rate for treatment appears to be relatively high
      (45%) and noncompletion was associated with higher recidivism. These results
      indicate significantly better outcomes for offenders receiving specialized
      treatment and are consistent with, and toward the lower end of, recidivism rates
      reported in local and international evaluation studies.

PMID- 21862524
TI  - Assessment of moral judgment and empathy in young sex offenders: a comparison of
      clinical judgment and test results.
AB  - Professional decision making in forensic clinical practice may have lifelong
      consequences for offenders. Although information on moral development is
      important for prediction of reoffending and referral to adequate treatment,
      conclusions regarding moral development are still largely based on unstructured
      clinical judgment instead of assessment instruments. For this study, the authors
      examined to what extent unstructured clinical judgment of both moral judgment and
      victim empathy concurred with test results in a group of young sex offenders.
      Moral judgment was measured with the Sociomoral Reflection Measure-Short Form
      (SRM-SF), whereas victim empathy was measured with an extended version of the
      Basic Empathy Scale (BES). No significant associations were found between
      clinical judgment of moral judgment and the mean scores on the SRM-SF. However,
      clinical judgment of victim empathy was significantly associated with victim
      empathy on the Victim Empathy Scale but not consistently in the expected
      direction. Juvenile sex offenders, who were judged by clinicians to show little
      victim empathy, displayed lower mean scores on the Victim Empathy Scale than
      juvenile sex offenders who were evaluated to lack victim empathy or to have
      intact victim empathy. This study showed unstructured clinical judgment of moral
      development not to concur with test results. To improve decision-making processes
      regarding moral development, clinicians are advised to rely on instruments that
      assess moral development to inform clinical judgment. Further research is needed
      to examine which predictions are more accurate and to establish the predictive
      validity of moral development evaluations.

PMID- 21862525
TI  - Lifetime criminal history of sex offenders seen for psychological assessment in
      five decades.
AB  - A sample of 2,190 sex offenders seen between 1966 and 2009 was compared on
      lifetime sexual and all offending, using charges, convictions, court appearances,
      and self-report as criteria. Of these various criteria, between 47.4% and 81.1%
      reoffended. Canadian child abuse reporting laws, which came into effect in the
      1980s, were associated with increased charges and convictions for offenders, who
      victimized children, and with a reduction in their longer term reoffense rates.
      Immigration and population mobility, use of aliases, study follow-up time, and
      self-reported undetected sex crimes influenced reoffense rates. Results indicate
      that sex offenders continued to have short prison sentences and/or spend little
      or no time incarcerated during the latter part of the 20th century.

PMID- 21862526
TI  - Place-based differences in the commission of recurrent animal cruelty.
AB  - Despite the recent surge in research linking animal and human acts of violence,
      relatively few studies have been conducted examining animal cruelty itself.
      Although several researchers have begun to identify some of the correlates of
      animal cruelty, few have attempted to understand how differences in the
      backgrounds of rural and urban residents have led to their abuse of animals.
      Using survey data from 180 inmates, this study examines how demographic
      characteristics, exposure to animal cruelty in childhood, and the target animal's
      relationship with the abuser have contributed to the frequency of acts of animal
      cruelty in urban- and rural-based settings. Unlike their urban counterparts,
      rural respondents who engaged in recurrent animal cruelty were more likely to
      have witnessed family members and/or friends abuse an animal. Moreover, rural
      respondents who engaged in recurrent animal cruelty abused pet and stray animals,
      whereas recurrent animal abusers who grew up in urban areas tended to abuse pets
      only. These findings suggest possible place-based differences in the etiology of
      recurrent animal cruelty.

PMID- 21862527
TI  - Creating an art therapy anger management protocol for male inmates through a
      collaborative relationship.
AB  - A training partnership was established with the Florida Department of Corrections
      in 2003, and over the ensuing years, art therapy graduate student interns from
      Florida State University's Graduate Art Therapy Program have been placed in local
      prisons at different times. Recently, the art therapy interns worked closely with
      the supervising psychologist in one prison to alleviate and redirect aggression
      by integrating cognitive-behavioral techniques with art therapy directives. The
      art therapy interns and the psychologist developed a curriculum using a
      combination of workbook exercises and art tasks to develop and increase the
      participants' anger management skills, the Art Therapy Anger Management Protocol.
      This article provides an overview of art therapy in prison, the cognitive
      behavioral approach to anger management with prison inmates, and how art therapy
      was used to support this approach. Examples of completed art tasks designed to
      correspond with the workbook curriculum are presented. Overall, this article
      presents the successful collaboration between the psychologist and art therapists
      and demonstrates how they facilitated improvement in the participants' anger
      management skills through this program.

PMID- 21862528
TI  - The Impulsive Lifestyle Counseling Program for Antisocial Behavior in Outpatient
      Substance Abuse Treatment.
AB  - Antisocial behavior is associated with low quality of life for the patient and
      with adverse effects on society and those close to the antisocial patient.
      However, most patients with antisocial behavior are not seen in treatment
      settings that focus on their personality but rather in criminal justice settings,
      substance-abuse treatment, and social welfare settings. This article describes
      the adaptation and implementation of a highly structured manualized treatment,
      Impulsive Lifestyle Counseling (ILC), based on the Lifestyle Issues program, a 10
      week psychoeducation program studied in prison settings. ILC consists of four
      sessions over 4 weeks and a booster session 8 weeks later. The goal of treatment
      is described to patients as "to help people identify their impulsive thoughts and
      lifestyle leading to problems with drug use, other people, and the police." Two
      clinical examples and reflections on our experiences with the training and
      implementation of the ILC program are presented. 

PMID- 21862529
TI  - Perceived causal relations: novel methodology for assessing client attributions
      about causal associations between variables including symptoms and functional
      impairment.
AB  - Researchers have argued that the investigation of causal interrelationships
      between symptoms may help explain the high comorbidity rate between certain
      psychiatric disorders. Clients' own attributions concerning the causal
      interrelationships linking the co-occurrence of their symptoms represent data
      that may inform their clinical case conceptualization, treatment, and
      psychological theory regarding the etiology of comorbid disorders. The present
      study developed and evaluated a novel psychological assessment methodology for
      measuring Perceived Causal Relations (PCR) and examined its psychometric
      properties as applied to the question of whether posttraumatic stress and anxiety
      symptoms represent causal risk factors for depressive symptoms in 225
      undergraduates. Participants attributed their symptoms of anxiety and
      posttraumatic reexperiencing as significant causes of their depressive symptoms.
      Exploratory analyses identified a listing of symptoms reliably attributed as
      significant causes of other symptoms and functional impairment, as well as a
      listing of symptoms reliably attributed as significant effects (outcomes) of
      other symptoms and functional impairment. The PCR method has promise as an
      idiographic approach to assessing the causes and consequences of comorbid
      psychiatric symptoms and associated functional impairment. Research is required
      to assess the relevance and replicate these findings in distinct psychiatric
      groups experiencing various symptomatic presentations. Future research may also
      examine PCR ratings associating other individual differences, for example,
      between measures of history (e.g., life events), life choices, and personality.

PMID- 21862530
TI  - Paper-and-pencil and web-based testing: the measurement invariance of the Big
      Five personality tests in applied settings.
AB  - This study investigates the measurement equivalence of a five-factor measure of
      personality across two groups applying for jobs, who completed the same
      questionnaire using either a paper-and-pencil (n = 429) or a web online answer
      format (n = 651). The data were collected using the Big Five Questionnaire-2 (BFQ
      2; which is a measure of the Five Factor Model) of personality traits. Multiple
      group confirmatory factor analysis was used to test for the equivalence of factor
      covariance and mean structures of the BFQ-2. Findings suggested that the Five
      Factor Model scales have the same measurement unit and origin across applicants
      using different administration modes. However, latent means were slightly higher
      for applicants who responded in a web and unproctored condition than for
      applicants who completed a paper-and-pencil version of the same test. Practical
      implications for personality assessment are discussed.

PMID- 21862533
TI  - Facing up to the prescription opioid crisis.

PMID- 21862532
TI  - Association between socioeconomic status, sex, and age at death from cystic
      fibrosis in England and Wales (1959 to 2008): cross sectional study.
AB  - OBJECTIVE: To determine the trend in the association between socioeconomic status
      and sex and median age at death from cystic fibrosis in England and Wales, over
      the past 50 years. DESIGN: Series of annual cross sectional studies of all
      registered deaths with a diagnosis of cystic fibrosis in England and Wales, from
      1959 to 2008. METHODS: We obtained national mortality data for cystic fibrosis
      from the Office for National Statistics. From 1959 to 2000, the Registrar
      General's Social Class coded socioeconomic status as manual or non-manual. From
      2001 onwards, the National Statistics Socioeconomic Classification was
      implemented and socioeconomic status was split into three groups: professional
      and managerial, intermediate, and routine and manual. We calculated median age at
      death for every study year. We calculated the effects of sex and socioeconomic
      status on the odds of death above the median age at death for every study decade
      using logistic regression. RESULTS: From 1959 to 2008, 6750 deaths were
      attributed to cystic fibrosis in England and Wales. Males were more likely to die
      above the annual median age at death than females (from 1959 to 1999, adjusted
      odds ratio for socioeconomic status 1.28, 95% confidence intervals 1.13 to 1.45;
      from 2000 to 2008, 1.57, 1.18 to 2.08). Individuals in the highest socioeconomic
      class were also more likely to die above the median age of death than those in
      the lowest socioeconomic class (from 1959 to 2000, adjusted odds ratio for sex
      2.50, 2.16 to 2.90; from 2001 to 2008, 1.89, 1.20 to 2.97). CONCLUSIONS:
      Socioeconomic status and sex remain strong determinants of survival from cystic
      fibrosis in England and Wales, and the magnitude of these effects does not appear
      to have substantially reduced over time.

PMID- 21862534
TI  - Conditioned tolerance to the effects of alcohol on inhibitory control in humans.
AB  - AIMS: To test whether the repeated consumption of alcohol in a particular
      environment leads to the emergence of a context-specific conditioned compensatory
      response (CCR) that can counter alcohol's impairment of inhibitory processes.
      METHODS: Twenty-four participants consumed an alcoholic drink (males: 0.65 g/kg;
      females: 0.57 g/kg) in one context on three sessions and a matched placebo drink
      in a different context on three other sessions. At test, participants were split
      into two groups and consumed a novel alcoholic drink either in the context
      previously paired with alcohol or the placebo-paired context. On all sessions,
      participants were tested on two computer-based tasks that measured response
      inhibition: an affective go/no-go task and a stop-signal task (SST). RESULTS:
      Over the conditioning trials, tolerance developed to alcohol's disinhibitory
      effects on the go/no-go task; moreover, on the test for conditioned responding,
      performance was less impaired for participants in the alcohol-paired versus the
      placebo-paired context. No tolerance was evident on the SST, and no CCR.
      CONCLUSION: Repeated consumption of alcohol in a particular environment can lead
      to the emergence of a context-specific CCR that counters some of alcohol's
      disinhibitory effects. Therefore, consuming alcohol in an unfamiliar context
      might produce stronger disinhibitory effects than would be apparent in a familiar
      drinking environment.

PMID- 21862535
TI  - What is this thing called agitation?

PMID- 21862536
TI  - Cost comparison of ranibizumab and bevacizumab.

PMID- 21862537
TI  - Formularies should list animal derived excipients of drugs.

PMID- 21862538
TI  - Pressure to work during short periods of sickness should be seen in perspective.

PMID- 21862539
TI  - Pain is not the only cause of distress in dementia.

PMID- 21862541
TI  - WHO definition of health remains fit for purpose.

PMID- 21862542
TI  - Health is state of physical, mental, and social wellbeing.

PMID- 21862543
TI  - Proposal for new definition of health.

PMID- 21862545
TI  - Manufacturer's reply to letter by Seed and colleagues.

PMID- 21862546
TI  - Let them eat cake.

PMID- 21862547
TI  - A parallel with patient choice.

PMID- 21862548
TI  - Consumption and aggression.

PMID- 21862549
TI  - New Zealand bans synthetic cannabinoids.

PMID- 21862550
TI  - The caregiver-provider relationship assessment: measuring family caregivers'
      perceptions of relationship quality with health care providers.
AB  - This article summarizes the development of the caregiver-provider relationship
      assessment (CPRA) designed to measure family caregivers' perceptions of
      relationship quality with health care providers. Using an online sample of family
      caregivers (n = 156), the patient reactions assessment (PRA) was adapted for use
      with family caregivers and subjected to principal component and reliability
      analyses. Analyses indicate that the CPRA factor structure is analogous to the
      original PRA scale, and Cronbach's alpha for the three CPRA subscales range from
      .85 to .91. The tool can be used by clinicians and researchers in efforts to help
      family caregivers become more effective communicators in health care contexts.

PMID- 21862551
TI  - Definitive erythropoiesis in the trunk of zebrafish embryos.

PMID- 21862554
TI  - Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and
      Cripto signaling.
AB  - The signaling pathway for Nodal, a ligand of the TGFbeta superfamily, plays a
      central role in regulating the differentiation and/or maintenance of stem cell
      types that can be derived from the peri-implantation mouse embryo. Extra
      embryonic endoderm stem (XEN) cells resemble the primitive endoderm of the
      blastocyst, which normally gives rise to the parietal and the visceral endoderm
      in vivo, but XEN cells do not contribute efficiently to the visceral endoderm in
      chimeric embryos. We have found that XEN cells treated with Nodal or Cripto
      (Tdgf1), an EGF-CFC co-receptor for Nodal, display upregulation of markers for
      visceral endoderm as well as anterior visceral endoderm (AVE), and can contribute
      to visceral endoderm and AVE in chimeric embryos. In culture, XEN cells do not
      express Cripto, but do express the related EGF-CFC co-receptor Cryptic (Cfc1),
      and require Cryptic for Nodal signaling. Notably, the response to Nodal is
      inhibited by the Alk4/Alk5/Alk7 inhibitor SB431542, but the response to Cripto is
      unaffected, suggesting that the activity of Cripto is at least partially
      independent of type I receptor kinase activity. Gene set enrichment analysis of
      genome-wide expression signatures generated from XEN cells under these treatment
      conditions confirmed the differing responses of Nodal- and Cripto-treated XEN
      cells to SB431542. Our findings define distinct pathways for Nodal and Cripto in
      the differentiation of visceral endoderm and AVE from XEN cells and provide new
      insights into the specification of these cell types in vivo.

PMID- 21862553
TI  - Mechanisms of thymus organogenesis and morphogenesis.
AB  - The thymus is the primary organ responsible for generating functional T cells in
      vertebrates. Although T cell differentiation within the thymus has been an area
      of intense investigation, the study of thymus organogenesis has made slower
      progress. The past decade, however, has seen a renewed interest in thymus
      organogenesis, with the aim of understanding how the thymus develops to form a
      microenvironment that supports T cell maturation and regeneration. This has
      prompted modern revisits to classical experiments and has driven additional
      genetic approaches in mice. These studies are making significant progress in
      identifying the molecular and cellular mechanisms that control specification,
      early organogenesis and morphogenesis of the thymus.

PMID- 21862555
TI  - Differentiated skeletal cells contribute to blastema formation during zebrafish
      fin regeneration.
AB  - The origin of cells that generate the blastema following appendage amputation has
      been a long-standing question in epimorphic regeneration studies. The blastema is
      thought to originate from either stem (or progenitor) cells or differentiated
      cells of various tissues that undergo dedifferentiation. Here, we investigate the
      origin of cells that contribute to the regeneration of zebrafish caudal fin
      skeletal elements. We provide evidence that the process of lepidotrichia (bony
      rays) regeneration is initiated as early as 24 hours post-amputation and that
      differentiated scleroblasts acquire a proliferative state, detach from the
      lepidotrichia surface, migrate distally, integrate into the blastema and
      dedifferentiate. These findings provide novel insights into the origin of cells
      in epimorphic appendage regeneration in zebrafish and suggest conservation of
      regeneration mechanisms between fish and amphibians.

PMID- 21862556
TI  - Lef1 is required for progenitor cell identity in the zebrafish lateral line
      primordium.
AB  - The zebrafish posterior lateral line (pLL) is a sensory system that comprises
      clusters of mechanosensory organs called neuromasts (NMs) that are
      stereotypically positioned along the surface of the trunk. The NMs are deposited
      by a migrating pLL primordium, which is organized into polarized rosettes (proto
      NMs). During migration, mature proto-NMs are deposited from the trailing part of
      the primordium, while progenitor cells in the leading part give rise to new proto
      NMs. Wnt signaling is active in the leading zone of the primordium and global Wnt
      inactivation leads to dramatic disorganization of the primordium and a loss of
      proto-NM formation. However, the exact cellular events that are regulated by the
      Wnt pathway are not known. We identified a mutant strain, lef1(nl2), that
      contains a lesion in the Wnt effector gene lef1. lef1(nl2) mutants lack posterior
      NMs and live imaging reveals that rosette renewal fails during later stages of
      migration. Surprisingly, the overall primordium patterning, as assayed by the
      expression of various markers, appears unaltered in lef1(nl2) mutants. Lineage
      tracing and mosaic analyses revealed that the leading cells (presumptive
      progenitors) move out of the primordium and are incorporated into NMs; this
      results in a decrease in the number of proliferating progenitor cells and
      eventual primordium disorganization. We concluded that Lef1 function is not
      required for initial primordium organization or migration, but is necessary for
      proto-NM renewal during later stages of pLL formation. These findings revealed a
      novel role for the Wnt signaling pathway during mechanosensory organ formation in
      zebrafish.

PMID- 21862557
TI  - Lef1-dependent Wnt/beta-catenin signalling drives the proliferative engine that
      maintains tissue homeostasis during lateral line development.
AB  - During tissue morphogenesis and differentiation, cells must self-renew while
      contemporaneously generating daughters that contribute to the growing tissue. How
      tissues achieve this precise balance between proliferation and differentiation
      is, in most instances, poorly understood. This is in part due to the difficulties
      in dissociating the mechanisms that underlie tissue patterning from those that
      regulate proliferation. In the migrating posterior lateral line primordium
      (PLLP), proliferation is predominantly localised to the leading zone. As cells
      emerge from this zone, they periodically organise into rosettes that subsequently
      dissociate from the primordium and differentiate as neuromasts. Despite this
      reiterative loss of cells, the primordium maintains its size through regenerative
      cell proliferation until it reaches the tail. In this study, we identify a null
      mutation in the Wnt-pathway transcription factor Lef1 and show that its activity
      is required to maintain proliferation in the progenitor pool of cells that
      sustains the PLLP as it undergoes migration, morphogenesis and differentiation.
      In absence of Lef1, the leading zone becomes depleted of cells during its
      migration leading to the collapse of the primordium into a couple of terminal
      neuromasts. We show that this behaviour resembles the process by which the PLLP
      normally ends its migration, suggesting that suppression of Wnt signalling is
      required for termination of neuromast production in the tail. Our data support a
      model in which Lef1 sustains proliferation of leading zone progenitors,
      maintaining the primordium size and defining neuromast deposition rate.

PMID- 21862558
TI  - Biological and mathematical modeling of melanocyte development.
AB  - We aim to evaluate environmental and genetic effects on the
      expansion/proliferation of committed single cells during embryonic development,
      using melanoblasts as a paradigm to model this phenomenon. Melanoblasts are a
      specific type of cell that display extensive cellular proliferation during
      development. However, the events controlling melanoblast expansion are still
      poorly understood due to insufficient knowledge concerning their number and
      distribution in the various skin compartments. We show that melanoblast expansion
      is tightly controlled both spatially and temporally, with little variation
      between embryos. We established a mathematical model reflecting the main cellular
      mechanisms involved in melanoblast expansion, including proliferation and
      migration from the dermis to epidermis. In association with biological
      information, the model allows the calculation of doubling times for melanoblasts,
      revealing that dermal and epidermal melanoblasts have short but different
      doubling times. Moreover, the number of trunk founder melanoblasts at E8.5 was
      estimated to be 16, a population impossible to count by classical biological
      approaches. We also assessed the importance of the genetic background by studying
      gain- and loss-of-function beta-catenin mutants in the melanocyte lineage. We
      found that any alteration of beta-catenin activity, whether positive or negative,
      reduced both dermal and epidermal melanoblast proliferation. Finally, we
      determined that the pool of dermal melanoblasts remains constant in wild-type and
      mutant embryos during development, implying that specific control mechanisms
      associated with cell division ensure half of the cells at each cell division to
      migrate from the dermis to the epidermis. Modeling melanoblast expansion revealed
      novel links between cell division, cell localization within the embryo and
      appropriate feedback control through beta-catenin.

PMID- 21862559
TI  - Knockdown of embryonic myosin heavy chain reveals an essential role in the
      morphology and function of the developing heart.
AB  - The expression and function of embryonic myosin heavy chain (eMYH) has not been
      investigated within the early developing heart. This is despite the knowledge
      that other structural proteins, such as alpha and beta myosin heavy chains and
      cardiac alpha actin, play crucial roles in atrial septal development and cardiac
      function. Most cases of atrial septal defects and cardiomyopathy are not
      associated with a known causative gene, suggesting that further analysis into
      candidate genes is required. Expression studies localised eMYH in the developing
      chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner
      and functional studies were carried out using electrical and calcium signalling
      methodologies. Knockdown in the early embryo led to abnormal atrial septal
      development and heart enlargement. Intriguingly, action potentials of the eMYH
      knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy
      chain knockdowns and controls. Although myofibrillogenesis appeared normal, in
      knockdown hearts the tissue integrity was affected owing to apparent focal points
      of myocyte loss and an increase in cell death. An expression profile of human
      skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the
      functional homologue of the chick eMYH gene. These data provide compelling
      evidence that eMYH plays a crucial role in important processes in the early
      developing heart and, hence, is a candidate causative gene for atrial septal
      defects and cardiomyopathy.

PMID- 21862560
TI  - Loss of MAP3K1 enhances proliferation and apoptosis during retinal development.
AB  - Precise coordination of progenitor cell proliferation and differentiation is
      essential for proper organ morphogenesis and function during mammalian
      development. The mitogen-activated protein kinase kinase kinase 1 (MAP3K1) has a
      well-established role in anterior eyelid development, as Map3k1-knockout mice
      have defective embryonic eyelid closure and an 'eye-open at birth' (EOB)
      phenotype. Here, we show that MAP3K1 is highly expressed in the posterior of the
      developing eye and is required for retina development. The MAP3K1-deficient mice
      exhibit increased proliferation and apoptosis, and Muller glial cell
      overproduction in the developing retinas. Consequently, the retinas of these mice
      show localized rosette-like arrangements in the outer nuclear layer, and develop
      abnormal vascularization, broken down retinal pigment epithelium, photoreceptor
      loss and early onset of retinal degeneration. Although the retinal defect is
      associated with increased cyclin D1 and CDK4/6 expression, and RB phosphorylation
      and E2F-target gene upregulation, it is independent of the EOB phenotype and of
      JNK. The retinal developmental defect still occurs in knockout mice that have
      undergone tarsorrhaphy, but is absent in compound mutant Map3k1(+/DeltaKD)Jnk1(-/
      ) and Map3k1(+/DeltaKD)Jnk(+/-)Jnk2(+/-) mice that have EOB and reduced JNK
      signaling. Our results unveil a novel role for MAP3K1 in which it crosstalks with
      the cell cycle regulatory pathways in the prevention of retina malformation and
      degeneration.

PMID- 21862561
TI  - Non-redundant function of dystroglycan and beta1 integrins in radial sorting of
      axons.
AB  - Radial sorting allows the segregation of axons by a single Schwann cell (SC) and
      is a prerequisite for myelination during peripheral nerve development. Radial
      sorting is impaired in models of human diseases, congenital muscular dystrophy
      (MDC) 1A, MDC1D and Fukuyama, owing to loss-of-function mutations in the genes
      coding for laminin alpha2, Large or fukutin glycosyltransferases, respectively.
      It is not clear which receptor(s) are activated by laminin 211, or glycosylated
      by Large and fukutin during sorting. Candidates are alphabeta1 integrins, because
      their absence phenocopies laminin and glycosyltransferase deficiency, but the
      topography of the phenotypes is different and beta1 integrins are not substrates
      for Large and fukutin. By contrast, deletion of the Large and fukutin substrate
      dystroglycan does not result in radial sorting defects. Here, we show that
      absence of dystroglycan in a specific genetic background causes sorting defects
      with topography identical to that of laminin 211 mutants, and recapitulating the
      MDC1A, MDC1D and Fukuyama phenotypes. By epistasis studies in mice lacking one or
      both receptors in SCs, we show that only absence of beta1 integrins impairs
      proliferation and survival, and arrests radial sorting at early stages, that
      beta1 integrins and dystroglycan activate different pathways, and that the
      absence of both molecules is synergistic. Thus, the function of dystroglycan and
      beta1 integrins is not redundant, but is sequential. These data identify
      dystroglycan as a functional laminin 211 receptor during axonal sorting and the
      key substrate relevant to the pathogenesis of glycosyltransferase congenital
      muscular dystrophies.

PMID- 21862562
TI  - MAB-10/NAB acts with LIN-29/EGR to regulate terminal differentiation and the
      transition from larva to adult in C. elegans.
AB  - In Caenorhabditis elegans, a well-defined pathway of heterochronic genes ensures
      the proper timing of stage-specific developmental events. During the final larval
      stage, an upregulation of the let-7 microRNA indirectly activates the terminal
      differentiation factor and central regulator of the larval-to-adult transition,
      LIN-29, via the downregulation of the let-7 target genes lin-41 and hbl-1. Here,
      we identify a new heterochronic gene, mab-10, and show that mab-10 encodes a NAB
      (NGFI-A-binding protein) transcriptional co-factor. MAB-10 acts with LIN-29 to
      control the expression of genes required to regulate a subset of differentiation
      events during the larval-to-adult transition, and we show that the NAB
      interaction domain of LIN-29 is conserved in Kruppel-family EGR (early growth
      response) proteins. In mammals, EGR proteins control the differentiation of
      multiple cell lineages, and EGR-1 acts with NAB proteins to initiate menarche by
      regulating the transcription of the luteinizing hormone beta subunit. Genome-wide
      association studies of humans and various studies of mouse recently have
      implicated the mammalian homologs of the C. elegans heterochronic gene lin-28 in
      regulating cellular differentiation and the timing of menarche. Our work suggests
      that human homologs of multiple C. elegans heterochronic genes might act in an
      evolutionarily conserved pathway to promote cellular differentiation and the
      onset of puberty.

PMID- 21862563
TI  - Regulation of tooth number by fine-tuning levels of receptor-tyrosine kinase
      signaling.
AB  - Much of our knowledge about mammalian evolution comes from examination of dental
      fossils, because the highly calcified enamel that covers teeth causes them to be
      among the best-preserved organs. As mammals entered new ecological niches, many
      changes in tooth number occurred, presumably as adaptations to new diets. For
      example, in contrast to humans, who have two incisors in each dental quadrant,
      rodents only have one incisor per quadrant. The rodent incisor, because of its
      unusual morphogenesis and remarkable stem cell-based continuous growth, presents
      a quandary for evolutionary biologists, as its origin in the fossil record is
      difficult to trace, and the genetic regulation of incisor number remains a
      largely open question. Here, we studied a series of mice carrying mutations in
      sprouty genes, the protein products of which are antagonists of receptor-tyrosine
      kinase signaling. In sprouty loss-of-function mutants, splitting of gene
      expression domains and reduced apoptosis was associated with subdivision of the
      incisor primordium and a multiplication of its stem cell-containing regions.
      Interestingly, changes in sprouty gene dosage led to a graded change in incisor
      number, with progressive decreases in sprouty dosage leading to increasing
      numbers of teeth. Moreover, the independent development of two incisors in
      mutants with large decreases in sprouty dosage mimicked the likely condition of
      rodent ancestors. Together, our findings indicate that altering genetic dosage of
      an antagonist can recapitulate ancestral dental characters, and that tooth number
      can be progressively regulated by changing levels of activity of a single signal
      transduction pathway.

PMID- 21862564
TI  - Insulators form gene loops by interacting with promoters in Drosophila.
AB  - Chromatin insulators are regulatory elements involved in the modulation of
      enhancer-promoter communication. The 1A2 and Wari insulators are located
      immediately downstream of the Drosophila yellow and white genes, respectively.
      Using an assay based on the yeast GAL4 activator, we have found that both
      insulators are able to interact with their target promoters in transgenic lines,
      forming gene loops. The existence of an insulator-promoter loop is confirmed by
      the fact that insulator proteins could be detected on the promoter only in the
      presence of an insulator in the transgene. The upstream promoter regions, which
      are required for long-distance stimulation by enhancers, are not essential for
      promoter-insulator interactions. Both insulators support basal activity of the
      yellow and white promoters in eyes. Thus, the ability of insulators to interact
      with promoters might play an important role in the regulation of basal gene
      transcription.

PMID- 21862565
TI  - Are we worrying about the right men and are the right men feeling worried?
      Conscious but not unconscious prostate anxiety predicts screening among men from
      three ethnic groups.
AB  - Anxieties regarding cancer and screening have been consistently linked in
      prostate screening behavior with cancer-related anxieties generally thought to be
      higher among minority men. To date, however, the literature linking cancer
      anxieties to screening among diverse men remains predicated on self-reported
      anxiety. Research has yet to consider how "accurate" the reporting of anxiety may
      be among distinct groups of men or the possibility that anxiety may influence
      prostate cancer (PC) screening behavior through conscious and nonconscious
      channels; the current study tested for discrepancies between self-report and
      Stroop-ascertained general- and prostate-specific anxiety and their links to
      screening among 180 U.S.-born African American, U.S.-born European American, and
      immigrant Jamaican men. Men provided self-report information regarding trait and
      prostate-related anxiety and completed an emotional Stroop task. Mixed model
      ANOVAs showed that while U.S.-born African Americans had few discrepancies
      between self-report and Stroop-ascertained anxiety, Jamaicans reported greater PC
      anxiety than indicated by Stroop performance, while the opposite was true among
      U.S.-born Europeans. As expected, self-reported (but not Stroop-ascertained) PC
      anxiety predicted screening in multivariate analysis. Although men from different
      age and ethnic groups varied in the discrepancy between self-reported and Stroop
      ascertained PC anxiety, the influence of avoidance-producing emotions appears to
      operate predominantly through conscious channels.

PMID- 21862566
TI  - Factors influencing Australian construction industry apprentices' dietary
      behaviors.
AB  - To date there has been a theoretical and empirical gap in workplace-centered
      health promotion research-particularly as it applies to blue-collar men's diets.
      To begin addressing the paucity of research, five qualitative focus groups (N =
      53) were conducted in Australian training colleges to explore the dietary
      behaviors of apprentices. Thematic analysis was used by the researcher who
      concludes that although some apprentices were health conscious and attempted to
      eat healthy foods, many had diets high in saturated fats and sugar. These types
      of diets are associated with increased risks for developing chronic disease and
      are associated with decreased life expectancy. As such it poses a serious
      challenge for health promoters. Apprentices' dietary practices were also found to
      be moderated by convenience, availability, and cost of foods in their
      environment. Their nutritional beliefs, significant others, colleagues in the
      workplace, and their body image also influence their food choices.

PMID- 21862567
TI  - Walking a high beam: the balance between employment stability, workplace
      flexibility, and nonresident father involvement.
AB  - Compared with resident fathers, nonresident fathers are more likely to be
      unemployed or underemployed and less likely, when they are employed, to have
      access to flexible work arrangements. Although lack of employment stability is
      associated with lower levels of father involvement, some research shows that
      increased stability at work without increased flexibility is negatively related
      to involvement. Using data from the Fragile Families and Child Wellbeing Study (N
      = 895), the authors examined the relationship between nonresident fathers'
      employment stability, workplace flexibility, and father involvement. Results
      indicate that workplace flexibility, but not employment stability, is associated
      with higher levels of involvement. Policy and practice implications are
      discussed.

PMID- 21862568
TI  - Integration of SNP genotyping confidence scores in IBD inference.
AB  - MOTIVATION: High-throughput single nucleotide polymorphism (SNP) arrays have
      become the standard platform for linkage and association analyses. The high SNP
      density of these platforms allows high-resolution identification of ancestral
      recombination events even for distant relatives many generations apart. However,
      such inference is sensitive to marker mistyping and current error detection
      methods rely on the genotyping of additional close relatives. Genotyping
      algorithms provide a confidence score for each marker call that is currently not
      integrated in existing methods. There is a need for a model that incorporates
      this prior information within the standard identical by descent (IBD) and
      association analyses. RESULTS: We propose a novel model that incorporates marker
      confidence scores within IBD methods based on the Lander-Green Hidden Markov
      Model. The novel parameter of this model is the joint distribution of confidence
      scores and error status per array. We estimate this probability distribution by
      applying a modified expectation-maximization (EM) procedure on data from nuclear
      families genotyped with Affymetrix 250K SNP arrays. The converged tables from two
      different genotyping algorithms are shown for a wide range of error rates. We
      demonstrate the efficacy of our method in refining the detection of IBD signals
      using nuclear pedigrees and distant relatives. AVAILABILITY: Plinke, a new
      version of Plink with an extended pairwise IBD inference model allowing per
      marker error probabilities is freely available at:
      http://bioinfo.bgu.ac.il/bsu/software/plinke. CONTACT: obirk@bgu.ac.il;
      markusb@bgu.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 21862569
TI  - Genetic predictors of controlled ovarian hyperstimulation: where do we stand
      today?
AB  - BACKGROUND: Nowadays, the use of IVF has improved the prospects of infertility
      treatment. The expected outcome of IVF depends greatly on the effectiveness of
      controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are
      used to induce folliculogenesis. The response to stimulation varies substantially
      among women and is difficult to predict. Several predictive markers of COH
      outcome have been proposed (e.g. maternal age and ovarian reserve), but the
      search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the
      effects of individual genetic variability on COH outcome and the potential for
      customizing therapy based on the patient's genome. METHODS: MEDLINE, EMBASE,
      DARE, CINAHL and the Cochrane Library, and references from relevant articles were
      investigated up to February 2011 regarding any common genetic variation and
      COH/IVF outcome. RESULTS: Several polymorphisms in genes involved in FSH
      signalling, estrogen biosynthesis, folliculogenesis, folate metabolism and other
      aspects influence the response to exogenous gonadotrophin administration,
      resulting in differences in COH and IVF outcomes. Nevertheless, the most studied
      polymorphism FSHR Asn680Ser is practically the only genetic marker, together with
      ESR1 PvuII T/C, that could be applied in clinical tests. CONCLUSIONS: Although
      data are accumulating with evidence suggesting that the ovarian response to COH
      is mediated by various polymorphisms, the optimal biomarkers and the efficacy of
      the tests still remain to be evaluated.

PMID- 21862570
TI  - Getting big on BPA: role for BPA in obesity?

PMID- 21862571
TI  - Does killing adipocytes kill the bad macrophages?

PMID- 21862572
TI  - Reflections on carl kupfer (1928-2011).

PMID- 21862573
TI  - Activation kinetics of RAF protein in the ternary complex of RAF, RAS-GTP, and
      kinase on the plasma membrane of living cells: single-molecule imaging analysis.
AB  - RAS is an important cell signaling molecule, regulating the activities of various
      effector proteins, including the kinase c-RAF (RAF). Despite the critical
      function of RAS signaling, the activation kinetics have not been analyzed
      experimentally in living cells for any of the RAS effectors. Here, we analyzed
      the kinetics of RAF activation on the plasma membrane in living HeLa cells after
      stimulation with EGF to activate RAS. RAF is recruited by the active form of RAS
      (RAS-GTP) from the cytoplasm to the plasma membrane through two RAS-binding sites
      (the RAS-binding domain and the cysteine-rich domain (CRD)) and is activated by
      its phosphorylation by still undetermined kinases on the plasma membrane. Using
      single-molecule imaging, we measured the dissociation time courses of GFP-tagged
      molecules of wild type RAF and fragments or mutants of RAF containing one or two
      of the three functional domains (the RAS-binding domain, the CRD, and the
      catalytic domain) to determine their interaction with membrane components. Each
      molecule showed a unique dissociation time course, indicating that both its
      interaction with RAS-GTP and its phosphorylation by the kinases are rate-limiting
      steps in RAF activation. Based on our experimental results, we propose a kinetic
      model for the activation of RAF. The model suggests the importance of the
      interaction between RAS-GTP and CRD for the effective activation of RAF, which is
      triggered by rapid RAS-GTP-induced conformational changes in RAF and the
      subsequent presentation of RAF to the kinase. The model also suggests necessary
      properties of the kinases that activate RAF.

PMID- 21862574
TI  - 93-kDa twin-domain serine protease inhibitor (Serpin) has a regulatory function
      on the beetle Toll proteolytic signaling cascade.
AB  - Serpins are protease inhibitors that play essential roles in the down-regulation
      of extracellular proteolytic cascades. The core serpin domain is highly
      conserved, and typical serpins are encoded with a molecular size of 35-50 kDa.
      Here, we describe a novel 93-kDa protein that contains two complete, tandemly
      arrayed serpin domains. This twin serpin, SPN93, was isolated from the larval
      hemolymph of the large beetle Tenebrio molitor. The N-terminal serpin domain of
      SPN93 forms a covalent complex with the Spatzle-processing enzyme, a terminal
      serine protease of the Toll signaling cascade, whereas the C-terminal serpin
      domain of SPN93 forms complexes with a modular serine protease and the Spatzle
      processing enzyme-activating enzyme, which are two different enzymes of the
      cascade. Consequently, SPN93 inhibited beta-1,3-glucan-mediated Toll proteolytic
      cascade activation in an in vitro system. Site-specific proteolysis of SPN93 at
      the N-terminal serpin domain was observed after activation of the Toll
      proteolytic cascade in vivo, and down-regulation of SPN93 by RNAi sensitized beta
      1,3-glucan-mediated larval death. Therefore, SPN93 is the first serpin that
      contains twin tandemly arrayed and functionally active serpin domains that have a
      regulatory role in the larval Toll proteolytic signaling cascade.

PMID- 21862575
TI  - 5' End-independent RNase J1 endonuclease cleavage of Bacillus subtilis model RNA.
AB  - Bacillus subtilis trp leader RNA is a small (140-nucleotide) RNA that results
      from attenuation of trp operon transcription upon binding of the regulatory TRAP
      complex. Previously, endonucleolytic cleavage by ribonuclease RNase J1 in a 3'
      proximal, single-stranded region was shown to be critical for initiation of trp
      leader RNA decay. RNase J1 is a dual-specificity enzyme, with both 5'
      exonucleolytic and endonucleolytic activities. Here, we provide in vivo and in
      vitro evidence that RNase J1 accesses its internal target site on trp leader RNA
      in a 5' end-independent manner. This has important implications for the role of
      RNase J1 in RNA decay. We also tested the involvement in trp leader RNA decay of
      the more recently discovered endonuclease RNase Y. Half-lives of several trp
      leader RNA constructs, which were designed to probe pathways of endonucleolytic
      versus exonucleolytic decay, were measured in an RNase Y-deficient mutant.
      Remarkably, the half-lives of these constructs were indistinguishable from their
      half-lives in an RNase J1-deficient mutant. These results suggest that lowering
      RNase Y concentration may affect RNA decay indirectly via an effect on RNase J1,
      which is thought to exist with RNase Y in a degradosome complex. To generalize
      our findings with trp leader RNA to other RNAs, we show that the mechanism of trp
      leader RNA decay is not dependent on TRAP binding.

PMID- 21862576
TI  - Interaction patches of procaspase-1 caspase recruitment domains (CARDs) are
      differently involved in procaspase-1 activation and receptor-interacting protein
      2 (RIP2)-dependent nuclear factor kappaB signaling.
AB  - Protein interaction domains belonging to the death domain-fold superfamily are
      six-helix bundles that mediate the assembly of large protein complexes involved
      in apoptotic and inflammatory signaling. Typically, death domains (DDs), a
      subfamily of the death domain-fold superfamily, harbor six delineated interaction
      patches on their surfaces that mediate three distinct and conserved types of
      interaction designated as types I, II, and III. Here, we show that caspase
      recruitment domains (CARDs), another subfamily of the death domain-fold
      superfamily, multimerize by employing at least two of the three reported
      interaction types that were identified in DDs. On the one hand, the CARD of
      procaspase-1 binds the apoptosis-associated speck-like protein containing a
      caspase recruitment domain (ASC) through a type I interaction that involves a
      patch surrounding residue Asp-27. On the other hand, the CARD of procaspase-1
      auto-oligomerizes through a type III interaction involving a patch surrounding
      residue Arg-45. This oligomerization allows binding of receptor-interacting
      protein 2 (RIP2). In addition, we show that a 1:1 interaction between ASC and
      procaspase-1 is sufficient for procaspase-1 to gain proteolytic activity, whereas
      the formation of a higher order CARD complex involving ASC, procaspase-1, and
      RIP2 is required for effective procaspase-1-mediated NF-kappaB activation. These
      findings indicate that the CARD of procaspase-1 is differently involved in the
      formation of procaspase-1 activating platforms and procaspase-1-mediated, RIP2
      dependent NF-kappaB activation.

PMID- 21862577
TI  - Advanced glycation end products (AGEs) induce apoptosis via a novel pathway:
      involvement of Ca2+ mediated by interleukin-8 protein.
AB  - Advanced glycation end products (AGEs) accumulate in diabetic patients due to
      high blood glucose levels and cause multiple deleterious effects. In this study,
      we provide evidence that the AGE increased cell death, one such deleterious
      effect. Methyl glyoxal-coupled human serum albumin (AGE-HSA) induced
      transcription factors such as NF-kappaB, NF-AT, and AP-1. AGE acts through its
      cell surface receptor, RAGE, and degranulates vesicular contents including
      interleukin-8 (IL-8). The number of RAGEs, as well as the amount of NF-kappaB
      activation, is low, but the cell death is higher in neuronal cells upon AGE
      treatment. Degranulated IL-8 acts through its receptors, IL-8Rs, and induces
      sequential events in cells: increase in intracellular Ca(2+), activation of
      calcineurin, dephosphorylation of cytoplasmic NF-AT, nuclear translocation of NF
      AT, and expression of FasL. Expressed FasL increases activity of caspases and
      induces cell death. Although AGE increases the amount of reactive oxygen
      intermediate, accompanying cell death is not dependent upon reactive oxygen
      intermediate. AGE induces autophagy, which partially protects cells from cell
      death. A novel mechanism of AGE-mediated cell death in different cell types,
      especially in neuronal cells where it is an early event, is provided here. Thus,
      this study may be important in several age-related neuronal diseases where AGE
      induced apoptosis is observed because of high amounts of AGE.

PMID- 21862578
TI  - Epigenetic control of the host gene by commensal bacteria in large intestinal
      epithelial cells.
AB  - Intestinal epithelial cells (IECs) are continuously exposed to large numbers of
      commensal bacteria but are relatively insensitive to them, thereby averting an
      excessive inflammatory reaction. We have previously reported that the
      hyporesponsiveness of a human IEC line to LPS was primarily the result of a down
      regulation of TLR4 gene transcription through epigenetic mechanisms. In the
      present study we show that DNA methylation in the 5' region of the TLR4 gene is
      significantly higher in IECs than in splenic cells in vivo. The methylation was
      shown to be dependent on the differentiation state of the IECs, as the
      differentiated IEC population that expressed higher levels of intestinal alkaline
      phosphatase (IAP) also displayed greater methylation and lower expression of the
      TLR4 gene than the undifferentiated population. The IAP(high), differentiated
      population also showed less abundant expression of CDX2, the transcription factor
      required for the development of the intestine, than the IAP(low),
      undifferentiated population. Overexpression of CDX2 in an IEC line decreased the
      methylation level of the TLR4 gene, increased transcriptional promoter activity
      of the gene, and increased responsiveness to the TLR4 ligand. Furthermore, the
      methylation level of the TLR4 gene was significantly lower in IECs of the large
      intestine of germ-free mice than in those of conventional mice, whereas the level
      in IECs of the small intestine was almost equal between these mice, indicating
      that commensal bacteria contribute to the maintenance of intestinal symbiosis by
      controlling epigenetic modification of the host gene in the large intestine.

PMID- 21862579
TI  - Polyubiquitin binding to optineurin is required for optimal activation of TANK
      binding kinase 1 and production of interferon beta.
AB  - TANK-binding kinase (TBK1) is essential for transcription of the interferon (IFN)
      beta gene in response to lipopolysaccharide (LPS) and double-stranded RNA, but
      the molecular mechanisms that underlie the activation of TBK1 are incompletely
      understood. Previously, we identified the NF-kappaB essential modulator (NEMO)
      related polyubiquitin-binding protein, optineurin (OPTN), as a novel binding
      partner of TBK1. To determine whether the ubiquitin-binding function of OPTN is
      involved in regulating TBK1 and IFNbeta production, we generated a mouse in which
      wild-type optineurin was replaced by the polyubiquitin binding-defective mutant,
      OPTN(D477N/D477N). In this study, we found that LPS or poly(I:C)-induced TBK1
      activity was significantly reduced in bone marrow-derived macrophage (BMDM) from
      OPTN(D477N/D477N) mice. Consistent with this, the phosphorylation of IFN
      regulatory factor 3 (IRF3) and the production of IFNbeta mRNA and secretion were
      reduced. Stimulation of BMDMs with LPS triggered the phosphorylation of OPTN,
      which was reversed by phosphatase treatment and prevented by pharmacological
      inhibition of both the canonical IkappaB kinases (IKKalpha/beta) and the IKK
      related kinases (TBK1/IKKepsilon). In contrast, LPS-stimulated phosphorylation of
      OPTN(D477N) was markedly reduced in BMDMs from OPTN(D477N/D477N) mice, and
      inhibition of the canonical IKKs alone prevented phosphorylation, providing
      further evidence that ubiquitin binding to OPTN contributes to LPS-induced TBK1
      activation. TBK1 and IKKbeta phosphorylated OPTN preferentially at Ser-177 and
      Ser-513, respectively, in vitro. In conclusion, our results suggest that OPTN
      binds to polyubiquitylated species formed in response to LPS and poly(I:C),
      enhancing the activation of TBK1 that is required for optimal phosphorylation of
      IRF3 and production of IFNbeta.

PMID- 21862580
TI  - Akt fine-tunes NF-kappaB-dependent gene expression during T cell activation.
AB  - Activation of the NF-kappaB signaling pathway is critical for leukocyte
      activation and development. Although previous studies suggested a role for the
      Akt kinase in coupling the T cell antigen receptor and CD28 to NF-kappaB
      activation in T cells, the nature of the role of Akt in this pathway is still
      unclear. Using a targeted gene profiling approach, we found that a subset of NF
      kappaB-dependent genes required Akt for optimal up-regulation during T cell
      activation. The selective effects of Akt were manifest at the level of mRNA
      transcription and p65/RelA binding to upstream promoters and appear to be due to
      altered formation of the Carma1-Bcl10 complex. The proinflammatory cytokine TNF
      alpha was found to be particularly sensitive to Akt inhibition or knockdown,
      including in primary human blood T cells and a murine model of rheumatoid
      arthritis. Our findings are consistent with a hierarchy in the expression of NF
      kappaB-dependent genes, controlled by the strength and/or duration of NF-kappaB
      signaling. More broadly, our results suggest that defining the more graded
      effects of signaling, such as those demonstrated here for Akt and the NF-kappaB
      pathway, is important to understanding how cells can fine-tune signaling
      responses for optimal sensitivity and specificity.

PMID- 21862581
TI  - A molecular chaperone mediates a two-protein enzyme complex and glycosylation of
      serine-rich streptococcal adhesins.
AB  - Serine-rich repeat glycoproteins identified from streptococci and staphylococci
      are important for bacterial adhesion and biofilm formation. Two putative
      glycosyltransferases, Gtf1 and Gtf2, from Streptococcus parasanguinis form a two
      protein enzyme complex that is required for glycosylation of a serine-rich repeat
      adhesin, Fap1. Gtf1 is a glycosyltransferase; however, the function of Gtf2 is
      unknown. Here, we demonstrate that Gtf2 enhances the enzymatic activity of Gtf1
      by its chaperone-like property. Gtf2 interacted with Gtf1, mediated the
      subcellular localization of Gtf1, and stabilized Gtf1. Deletion of invariable
      amino acid residues in a conserved domain of unknown function (DUF1975) at the N
      terminus of Gtf2 had a greater impact on Fap1 glycosylation than deletion of the
      C-terminal non-DUF1975 residues. The DUF1975 deletions concurrently reduced the
      interaction between Gtf1 and Gtf2, altered the subcellular localization of Gtf1,
      and destabilized Gtf1, suggesting that DUF1975 is crucial for the chaperone
      activity of Gtf2. Homologous GtfA and GtfB from Streptococcus agalactiae rescued
      the glycosylation defect in the gtf1gtf2 mutant; like Gtf2, GtfB also possesses
      chaperone-like activity. Taken together, our studies suggest that Gtf2 and its
      homologs possess the conserved molecular chaperone activity that mediates protein
      glycosylation of bacterial adhesins.

PMID- 21862582
TI  - Chitosan but not chitin activates the inflammasome by a mechanism dependent upon
      phagocytosis.
AB  - Chitin is an abundant polysaccharide found in fungal cell walls, crustacean
      shells, and insect exoskeletons. The immunological properties of both chitin and
      its deacetylated derivative chitosan are of relevance because of frequent natural
      exposure and their use in medical applications. Depending on the preparation
      studied and the end point measured, these compounds have been reported to induce
      allergic responses, inflammatory responses, or no response at all. We prepared
      highly purified chitosan and chitin and examined the capacity of these glycans to
      stimulate murine macrophages to release the inflammasome-associated cytokine IL
      1beta. We found that although chitosan was a potent NLRP3 inflammasome activator,
      acetylation of the chitosan to chitin resulted in a near total loss of activity.
      The size of the chitosan particles played an important role, with small particles
      eliciting the greatest activity. An inverse relationship between size and
      stimulatory activity was demonstrated using chitosan passed through size
      exclusion filters as well as with chitosan-coated beads of defined size. Partial
      digestion of chitosan with pepsin resulted in a larger fraction of small
      phagocytosable particles and more potent inflammasome activity. Inhibition of
      phagocytosis with cytochalasin D abolished the IL-1beta stimulatory activity of
      chitosan, offering an explanation for why the largest particles were nearly
      devoid of activity. Thus, the deacetylated polysaccharide chitosan potently
      activates the NLRP3 inflammasome in a phagocytosis-dependent manner. In contrast,
      chitin is relatively inert.

PMID- 21862583
TI  - Increased bone mass in mice after single injection of anti-receptor activator of
      nuclear factor-kappaB ligand-neutralizing antibody: evidence for bone anabolic
      effect of parathyroid hormone in mice with few osteoclasts.
AB  - Receptor activator of nuclear factor-kappaB ligand (RANKL) is a pivotal
      osteoclast differentiation factor. To investigate the effect of RANKL inhibition
      in normal mice, we prepared an anti-mouse RANKL-neutralizing monoclonal antibody
      (Mab, clone OYC1) and established a new mouse model with high bone mass induced
      by administration of OYC1. A single subcutaneous injection of 5 mg/kg OYC1 in
      normal mice significantly augmented the bone mineral density in the distal
      femoral metaphysis from day 2 to day 28. The OYC1 treatment markedly reduced the
      serum level of tartrate-resistant acid phosphatase-5b (TRAP-5b, a marker for
      osteoclasts) on day 1, and this level was undetectable from day 3 to day 28. The
      serum level of alkaline phosphatase (a marker for osteoblasts) declined
      significantly following the reduction of TRAP-5b. Histological analysis revealed
      few osteoclasts in femurs of the treated mice on day 4, and both osteoclasts and
      osteoblasts were markedly diminished on day 14. Daily injection of parathyroid
      hormone for 2 weeks increased the bone mineral density in trabecular and cortical
      bone by stimulating bone formation in the OYC1-treated mice. These results
      suggest that parathyroid hormone exerted its bone anabolic activity in mice with
      few osteoclasts. The mouse anti-RANKL neutralizing antibody OYC1 may be a useful
      tool to investigate unknown functions of RANKL in vivo.

PMID- 21862584
TI  - The RNA-binding protein HuR stabilizes cytosolic phospholipase A2alpha mRNA under
      interleukin-1beta treatment in non-small cell lung cancer A549 Cells.
AB  - The activation of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) plays an
      important role in initiating the inflammatory response. The regulation of
      cPLA(2)alpha mRNA turnover has been proposed to control cPLA(2)alpha gene
      expression under cytokine and growth factor stimulation. However, the detailed
      mechanism is still unknown. In this report, we have demonstrated that the
      cPLA(2)alpha mRNA stability was increased under IL-1beta treatment in A549 cells.
      By using EMSAs, HuR was identified as binding with the cPLA(2)alpha mRNA 3'-UTR,
      and the binding region was located at nucleotides 2716-2807, a fragment
      containing AUUUA flanked by U-rich sequences. IL-1beta treatment enhanced the
      association of cPLA(2)alpha mRNA with cytosolic HuR. The reduction of HuR
      expression by RNA interference technology inhibited IL-1beta-induced cPLA(2)alpha
      mRNA and protein expression. Furthermore, blocking the p38 MAPK signaling pathway
      with SB203580 abolished the effect of IL-1beta-induced cPLA(2)alpha gene
      expression. Phosphorylation at residue Thr-118 of HuR is crucial in regulating
      the interaction between HuR and its target mRNAs. Mutation of HuR Thr-118 reduced
      the association between HuR and cPLA(2)alpha mRNA under IL-1beta treatment. This
      inhibitory effect was also observed in binding with COX-2 mRNA. This result
      indicated that p38 MAPK-mediated Thr-118 phosphorylation may play a key role in
      regulating the interaction of HuR with its target mRNAs in inflammation.

PMID- 21862585
TI  - Access to the complement factor B scissile bond is facilitated by association of
      factor B with C3b protein.
AB  - Factor B is a zymogen that carries the catalytic site of the complement
      alternative pathway C3 convertase. During convertase assembly, factor B
      associates with C3b and Mg(2+) forming a pro-convertase C3bB(Mg(2+)) that is
      cleaved at a single factor B site by factor D. In free factor B, a pair of salt
      bridges binds the Arg(234) side chain to Glu(446) and to Glu(207), forming a
      double latch structure that sequesters the scissile bond (between Arg(234) and
      Lys(235)) and minimizes its unproductive cleavage. It is unknown how the double
      latch is released in the pro-convertase. Here, we introduce single amino acid
      substitutions into factor B that preclude one or both of the Arg(234) salt
      bridges, and we examine their impact on several different pro-convertase
      complexes. Our results indicate that loss of the Arg(234)-Glu(446) salt bridge
      partially stabilizes C3bB(Mg(2+)). Loss of the Arg(234)-Glu(207) salt bridge has
      lesser effects. We propose that when factor B first associates with C3b, it bears
      two intact Arg(234) salt bridges. The complex rapidly dissociates unless the
      Arg(234)-Glu(446) salt bridge is released whereupon conformational changes occur
      that activate the metal ion-dependent adhesion site and partially stabilize the
      complex. The remaining salt bridge is then released, exposing the scissile bond
      and permitting factor D cleavage.

PMID- 21862586
TI  - Pathogen-specific TLR2 protein activation programs macrophages to induce Wnt-beta
      catenin signaling.
AB  - Innate immunity recognizes and resists various pathogens; however, the mechanisms
      regulating pathogen versus nonpathogen discrimination are still imprecisely
      understood. Here, we demonstrate that pathogen-specific activation of TLR2 upon
      infection with Mycobacterium bovis BCG, in comparison with other pathogenic
      microbes, including Salmonella typhimurium and Staphylococcus aureus, programs
      macrophages for robust up-regulation of signaling cohorts of Wnt-beta-catenin
      signaling. Signaling perturbations or genetic approaches suggest that infection
      mediated stimulation of Wnt-beta-catenin is vital for activation of Notch1
      signaling. Interestingly, inducible NOS (iNOS) activity is pivotal for TLR2
      mediated activation of Wnt-beta-catenin signaling as iNOS(-/-) mice demonstrated
      compromised ability to trigger activation of Wnt-beta-catenin signaling as well
      as Notch1-mediated cellular responses. Intriguingly, TLR2-driven integration of
      iNOS/NO, Wnt-beta-catenin, and Notch1 signaling contributes to its capacity to
      regulate the battery of genes associated with T(Reg) cell lineage commitment.
      These findings reveal a role for differential stimulation of TLR2 in deciding the
      strength of Wnt-beta-catenin signaling, which together with signals from Notch1
      contributes toward the modulation of a defined set of effector functions in
      macrophages and thus establishes a conceptual framework for the development of
      novel therapeutics.

PMID- 21862587
TI  - Caenorhabditis elegans UCP4 protein controls complex II-mediated oxidative
      phosphorylation through succinate transport.
AB  - The novel uncoupling proteins (UCP2-5) are implicated in the mitochondrial
      control of oxidant production, insulin signaling, and aging. Attempts to
      understand their functions have been complicated by overlapping expression
      patterns in most organisms. Caenorhabditis elegans nematodes are unique because
      they express only one UCP ortholog, ceUCP4 (ucp4). Here, we performed detailed
      metabolic analyzes in genetically modified nematodes to define the function of
      the ceUCP4. The knock-out mutant ucp4 (ok195) exhibited sharply decreased
      mitochondrial succinate-driven (complex II) respiration. However, respiratory
      coupling and electron transport chain function were normal in ucp4 mitochondria.
      Surprisingly, isolated ucp4 mitochondria showed markedly decreased succinate
      uptake. Similarly, ceUCP4 inhibition blocked succinate respiration and import in
      wild type mitochondria. Genetic and pharmacologic inhibition of complex I
      function was selectively lethal to ucp4 worms, arguing that ceUCP4-regulated
      succinate transport is required for optimal complex II function in vivo.
      Additionally, ceUCP4 deficiency prolonged lifespan in the short-lived mev1 mutant
      that exhibits complex II-generated oxidant production. These results identify a
      novel function for ceUCP4 in the regulation of complex II-based metabolism
      through an unexpected mechanism involving succinate transport.

PMID- 21862588
TI  - Anti-Ro52 autoantibodies from patients with Sjogren's syndrome inhibit the Ro52
      E3 ligase activity by blocking the E3/E2 interface.
AB  - Ro52 (TRIM21) is an E3 ligase of the tripartite motif family that negatively
      regulates proinflammatory cytokine production by ubiquitinating transcription
      factors of the interferon regulatory factor family. Autoantibodies to Ro52 are
      present in patients with lupus and Sjogren's syndrome, but it is not known if
      these autoantibodies affect the function of Ro52. To address this question, the
      requirements for Ro52 E3 ligase activity were first analyzed in detail. Scanning
      a panel of E2 ubiquitin-conjugating enzymes, we found that UBE2D1-4 and UBE2E1-2
      supported the E3 ligase activity of Ro52 and that the E3 ligase activity of Ro52
      was dependent on its RING domain. We also found that the N-terminal extensions in
      the class III E2 enzymes affected their interaction with Ro52. Although the N
      terminal extension in UBE2E3 made this E2 enzyme unable to function together with
      Ro52, the N-terminal extensions in UBE2E1 and UBE2E2 allowed for a functional
      interaction with Ro52. Anti-Ro52-positive patient sera and affinity-purified anti
      RING domain autoantibodies inhibited the E3 activity of Ro52 in ubiquitination
      assays. Using NMR, limited proteolysis, ELISA, and Ro52 mutants, we mapped the
      interactions between Ro52, UBE2E1, and anti-Ro52 autoantibodies. We found that
      anti-Ro52 autoantibodies inhibited the E3 ligase activity of Ro52 by sterically
      blocking the E2/E3 interaction between Ro52 and UBE2E1. Our data suggest that
      anti-Ro52 autoantibodies binding the RING domain of Ro52 may be actively involved
      in the pathogenesis of rheumatic autoimmune disease by inhibiting Ro52-mediated
      ubiquitination.

PMID- 21862589
TI  - Role of amino-terminal half of the S4-S5 linker in type 1 ryanodine receptor
      (RyR1) channel gating.
AB  - The type 1 ryanodine receptor (RyR1) is a Ca(2+) release channel found in the
      sarcoplasmic reticulum of skeletal muscle and plays a pivotal role in excitation
      contraction coupling. The RyR1 channel is activated by a conformational change of
      the dihydropyridine receptor upon depolarization of the transverse tubule, or by
      Ca(2+) itself, i.e. Ca(2+)-induced Ca(2+) release (CICR). The molecular events
      transmitting such signals to the ion gate of the channel are unknown. The S4-S5
      linker, a cytosolic loop connecting the S4 and S5 transmembrane segments in six
      transmembrane type channels, forms an alpha-helical structure and mediates signal
      transmission in a wide variety of channels. To address the role of the S4-S5
      linker in RyR1 channel gating, we performed alanine substitution scan of N
      terminal half of the putative S4-S5 linker (Thr(4825)-Ser(4829)) that exhibits
      high helix probability. The mutant RyR1 was expressed in HEK cells, and CICR
      activity was investigated by caffeine-induced Ca(2+) release, single-channel
      current recordings, and [(3)H]ryanodine binding. Four mutants (T4825A, I4826A,
      S4828A, and S4829A) had reduced CICR activity without changing Ca(2+)
      sensitivity, whereas the L4827A mutant formed a constitutive active channel.
      T4825I, a disease-associated mutation for malignant hyperthermia, exhibited
      enhanced CICR activity. An alpha-helical wheel representation of the N-terminal
      S4-S5 linker provides a rational explanation to the observed activities of the
      mutants. These results suggest that N-terminal half of the S4-S5 linker may form
      an alpha-helical structure and play an important role in RyR1 channel gating.

PMID- 21862590
TI  - Overexpression of KLF15 transcription factor in adipocytes of mice results in
      down-regulation of SCD1 protein expression in adipocytes and consequent
      enhancement of glucose-induced insulin secretion.
AB  - Kruppel-like factor 15 (KLF15), a member of the Kruppel-like factor family of
      transcription factors, has been found to play diverse roles in adipocytes in
      vitro. However, little is known of the function of KLF15 in adipocytes in vivo.
      We have now found that the expression of KLF15 in adipose tissue is down
      regulated in obese mice, and we therefore generated adipose tissue-specific KLF15
      transgenic (aP2-KLF15 Tg) mice to investigate the possible contribution of KLF15
      to various pathological conditions associated with obesity in vivo. The aP2-KLF15
      Tg mice manifest insulin resistance and are resistant to the development of
      obesity induced by maintenance on a high fat diet. However, they also exhibit
      improved glucose tolerance as a result of enhanced insulin secretion.
      Furthermore, this enhancement of insulin secretion was shown to result from down
      regulation of the expression of stearoyl-CoA desaturase 1 (SCD1) in white adipose
      tissue and a consequent reduced level of oxidative stress. This is supported by
      the findings that restoration of SCD1 expression in white adipose tissue of aP2
      KLF15 Tg mice exhibited increased oxidative stress in white adipose tissue and
      reduced insulin secretion with hyperglycemia. Our data thus provide an example of
      cross-talk between white adipose tissue and pancreatic beta cells mediated
      through modulation of oxidative stress.

PMID- 21862591
TI  - Inhibition of glycolytic enzymes mediated by pharmacologically activated p53:
      targeting Warburg effect to fight cancer.
AB  - Unique sensitivity of tumor cells to the inhibition of glycolysis is a good
      target for anticancer therapy. Here, we demonstrate that the pharmacologically
      activated tumor suppressor p53 mediates the inhibition of glycolytic enzymes in
      cancer cells in vitro and in vivo. We showed that p53 binds to the promoters of
      metabolic genes and represses their expression, including glucose transporters
      SLC2A12 (GLUT12) and SLC2A1 (GLUT1). Furthermore, p53-mediated repression of
      transcription factors c-Myc and HIF1alpha, key drivers of ATP-generating pathways
      in tumors, contributed to ATP production block. Inhibition of c-Myc by p53
      mediated the ablation of several glycolytic genes in normoxia, whereas in hypoxia
      down-regulation of HIF1alpha contributed to this effect. We identified Sp1 as a
      transcription cofactor cooperating with p53 in the ablation of metabolic genes.
      Using different approaches, we demonstrated that glycolysis block contributes to
      the robust induction of apoptosis by p53 in cancer cells. Taken together, our
      data suggest that tumor-specific reinstatement of p53 function targets the
      "Achilles heel" of cancer cells (i.e. their dependence on glycolysis), which
      could contribute to the tumor-selective killing of cancer cells by
      pharmacologically activated p53.

PMID- 21862592
TI  - InvA protein is a Nudix hydrolase required for infection by pathogenic Leptospira
      in cell lines and animals.
AB  - Leptospirosis caused by pathogenic species of the genus Leptospira is a re
      emerging zoonotic disease, which affects a wide variety of host species and is
      transmitted by contaminated water. The genomes of several pathogenic Leptospira
      species contain a gene named invA, which contains a Nudix domain. However, the
      function of this gene has never been characterized. Here, we demonstrated that
      the invA gene was highly conserved in protein sequence and present in all tested
      pathogenic Leptospira species. The recombinant InvA protein of pathogenic L.
      interrogans strain Lai hydrolyzed several specific dinucleoside oligophosphate
      substrates, reflecting the enzymatic activity of Nudix in Leptospira species.
      Pathogenic leptospires did not express this protein in media but temporarily
      expressed it at early stages (within 60 min) of infection of macrophages and
      nephric epithelial cells. Comparing with the wild type, the invA-deficient mutant
      displayed much lower infectivity and a significantly reduced survival rate in
      macrophages and nephric epithelial cells. Moreover, the invA-deficient
      leptospires presented an attenuated virulence in hamsters, caused mild
      histopathological damage, and were transmitted in lower numbers in the urine,
      compared with the wild-type strain. The invA revertant, made by complementing the
      invA-deficient mutant with the invA gene, reacquired virulence similar to the
      wild type in vitro and in vivo. The LD(50) in hamsters was 1000-fold higher for
      the invA-deficient mutant than for the invA revertant and wild type. These
      results demonstrate that the InvA protein is a Nudix hydrolase, and the invA gene
      is essential for virulence in pathogenic Leptospira species.

PMID- 21862594
TI  - Molecular mechanisms for synchronized transcription of three complement C1q
      subunit genes in dendritic cells and macrophages.
AB  - Hereditary homozygous C1q deficiency is rare, but it almost certainly causes
      systemic lupus erythematosus. On the other hand, C1q levels can decline in
      systemic lupus erythematosus patients without apparent C1q gene defects and the
      versatility in C1q production is a likely cause. As an 18-subunit protein, C1q is
      assembled in a 1:1:1 ratio from three different subunits. The three human C1q
      genes are closely bundled on chromosome 1 (C1qA-C1qC-C1qB) and their basal and
      IFNgamma-stimulated expression, largely restricted to macrophages and dendritic
      cells, is apparently synchronized. We cloned the three gene promoters and
      observed that although the C1qB promoter exhibited basal and IFNgamma-stimulated
      activities consistent with the endogenous C1qB gene, the activities of the cloned
      C1qA and C1qC promoters were suppressed by IFNgamma. To certain extents, these
      were corrected when the C1qB promoter was cloned at the 3' end across the
      luciferase reporter gene. A 53-bp element is essential to the activities of the
      C1qB promoter and the transcription factors PU.1 and IRF8 bound to this region.
      By chromatin immunoprecipitation, the C1qB promoter was co-precipitated with PU.1
      and IRF8. shRNA knockdown of PU.1 and IRF8 diminished C1qB promoter response to
      IFNgamma. STAT1 instead regulated C1qB promoter through IRF8 induction.
      Collectively, our results reveal a novel transcriptional mechanism by which the
      expression of the three C1q genes is synchronized.

PMID- 21862593
TI  - Auto-activation of c-JUN gene by amino acid deprivation of hepatocellular
      carcinoma cells reveals a novel c-JUN-mediated signaling pathway.
AB  - Mammalian cells respond to protein or amino acid (AA) limitation by activating a
      number of signaling pathways, collectively referred to as the AA response (AAR),
      that modulate a range of cellular functions, including transcriptional induction
      of target genes. This study demonstrates that in hepatocellular carcinoma cells,
      expression of c-JUN, JUN-B, c-FOS, and FOS-B was induced by the AAR, whereas JUN
      D, FRA-1, and FRA-2 were not. Of the four activated FOS/JUN members, c-JUN made
      the largest contribution to the induction of several known AAR target genes. For
      several human liver, prostate, and ovarian cell lines, the AAR-induced increase
      in c-JUN expression was greater in transformed cells compared with nontransformed
      counterparts, an effect independent of cell growth rate. Thus far, the best
      characterized AA-responsive genes are all transcriptionally activated by ATF4,
      but the AAR-dependent induction of c-JUN transcription was ATF4-independent. The
      increased expression of c-JUN was dependent on ATF2 and on activation of the MEK
      ERK and JNK arms of the MAPK signaling pathways. Formation of c-JUN-ATF2
      activated heterodimers was increased after AA limitation, and c-JUN or ATF2
      knockdown suppressed the induction of c-JUN and other AAR target genes. AA
      deprivation triggers a feed-forward process that involves phosphorylation of
      existing c-JUN protein by JNK and subsequent auto-activation of the c-JUN gene by
      recruitment of c-JUN and ATF2 to two AP-1 sites within the proximal promoter. The
      results document the novel observation that AP-1 sequences within the c-JUN gene
      can function as transcriptional amino acid-response elements.

PMID- 21862595
TI  - Histone 3 lysine 9 (H3K9) methyltransferase recruitment to the interleukin-2 (IL
      2) promoter is a mechanism of suppression of IL-2 transcription by the
      transforming growth factor-beta-Smad pathway.
AB  - Suppression of IL-2 betaproduction from T cells is an important process for the
      immune regulation by TGF-beta. However, the mechanism by which this suppression
      occurs remains to be established. Here, we demonstrate that Smad2 and Smad3, two
      major TGF-beta-downstream transcription factors, are redundantly essential for
      TGF-beta-mediated suppression of IL-2 production in CD4(+) T cells using Smad2-
      and Smad3-deficient T cells. Both Smad2 and Smad3 were recruited into the
      proximal region of the IL-2 promoter in response to TGF-beta. We then
      investigated the histone methylation status of the IL-2 promoter. Although both
      histone H3 lysine 9 (H3K9) and H3K27 trimethylation have been implicated in gene
      silencing, only H3K9 trimethylation was increased in the proximal region of the
      IL-2 promoter in a Smad2/3-dependent manner, whereas H3K27 trimethylation was
      not. The H3K9 methyltransferases Setdb1 and Suv39h1 bound to Smad3 and suppressed
      IL-2 promoter activity in collaboration with Smad3. Overexpression of Suv39h1 in
      68-41 T cells strongly inhibited IL-2 production in response to T cell receptor
      stimulation irrespective of the presence or absence of TGF-beta, whereas Setdb1
      overexpression only slightly suppressed IL-2 production. Silencing of Suv39h1 by
      shRNA reverted the suppressive effect of TGF-beta on IL-2 production.
      Furthermore, TGF-beta induced Suv39h1 recruitment to the proximal region of the
      IL-2 promoter in wild type primary T cells; however, this was not observed in
      Smad2(-/-)Smad3(+/-) T cells. Thus, we propose that Smads recruit H3K9
      methyltransferases Suv39h1 to the IL-2 promoter, thereby inducing suppressive
      histone methylation and inhibiting T cell receptor-mediated IL-2 transcription.

PMID- 21862596
TI  - Activation of the IkappaB kinase complex by HTLV-1 Tax requires cytosolic factors
      involved in Tax-induced polyubiquitination.
AB  - Activation of NF-kappaB by human T cell leukaemia virus type 1 Tax is thought to
      be crucial in T-cell transformation and the onset of adult T cell leukaemia. Tax
      activates NF-kappaB through activation of the IkappaB kinase (IKK) complex,
      similar to cytokine-induced NF-kappaB activation, which involves active
      signalling complex formation using polyubiquitin chains as a platform. Although
      polyubiquitination of Tax was reported to be required for IKK activation, most
      studies have been performed using intact cells, in which secondary NF-kappaB
      activation can be induced by various cytokines that are secreted due to Tax
      mediated primary NF-kappaB activation. Therefore, a cell-free assay system, in
      which IKK can be activated by adding highly purified recombinant Tax to cytosolic
      extract, was used to analyse Tax-induced IKK activation. In contrast to the
      cytosolic extract, the purified IKK complex was not activated by Tax, whereas, it
      was efficiently activated by MEKK1, that does not require polyubiquitination to
      activate IKK. Moreover, Tax-induced IKK activation was blocked when the cytosolic
      extract was mixed with either lysine-free, methylated or K63R ubiquitin. These
      results obtained through our cell-free assay suggest that K63-linked
      polyubiquitination is critical, but linear polyubiquitination is dispensable or
      insufficient for Tax-induced IKK activation.

PMID- 21862597
TI  - A novel post-exposure medical countermeasure L-97-1 improves survival and acute
      lung injury following intratracheal infection with Yersinia pestis.
AB  - Yersinia pestis, a Gram-negative bacillus causing plague and Centers for Disease
      Control and Prevention (CDC) classified Category A pathogen, has high potential
      as a bioweapon. Lipopolysaccharide, a virulence factor for Y. pestis, binds to
      and activates A(1) adenosine receptor (AR)s and, in animals, A(1)AR antagonists
      block induced acute lung injury (ALI) and increase survival following cecal
      ligation and perforation. In this study, rats were infected intratracheally with
      viable Y. pestis [CO99 (pCD1( + )/Deltapgm) 1 * 10( 8 ) CFU/animal] and treated
      daily for 3 d with ciprofloxacin (cipro), the A(1)AR antagonist L-97-1, or cipro
      plus L-97-1 starting at 0, 6, 24, 48, or 72 h post-Y. pestis. At 72 h post-Y.
      pestis, cipro plus L-97-1 significantly improved 6-d survival to 60-70% vs 28%
      for cipro plus H(2)O and 33% for untreated Y. pestis controls (P = 0.02, logrank
      test). Lung edema, hemorrhage and leukocyte infiltration index (LII) were
      evaluated histologically to produce ALI scores. Cipro plus L-97-1 significantly
      reduced lung edema, as well as aggregate lung injury scores vs controls or cipro
      plus H(2)O, and LII vs controls (P < 0.05, Student's unpaired t test). These
      results support efficacy for L-97-1 as a post-exposure medical countermeasure,
      adjunctive therapy to antibiotics for Y. pestis.

PMID- 21862598
TI  - Analysis of variance of communication latencies in anesthesia: comparing means of
      multiple log-normal distributions.
AB  - Anesthesiologists rely on communication over periods of minutes. The analysis of
      latencies between when messages are sent and responses obtained is an essential
      component of practical and regulatory assessment of clinical and managerial
      decision-support systems. Latency data including times for anesthesia providers
      to respond to messages have moderate (> n = 20) sample sizes, large coefficients
      of variation (e.g., 0.60 to 2.50), and heterogeneous coefficients of variation
      among groups. Highly inaccurate results are obtained both by performing analysis
      of variance (ANOVA) in the time scale or by performing it in the log scale and
      then taking the exponential of the result. To overcome these difficulties, one
      can perform calculation of P values and confidence intervals for mean latencies
      based on log-normal distributions using generalized pivotal methods. In addition,
      fixed-effects 2-way ANOVAs can be extended to the comparison of means of log
      normal distributions. Pivotal inference does not assume that the coefficients of
      variation of the studied log-normal distributions are the same, and can be used
      to assess the proportional effects of 2 factors and their interaction. Latency
      data can also include a human behavioral component (e.g., complete other activity
      first), resulting in a bimodal distribution in the log-domain (i.e., a mixture of
      distributions). An ANOVA can be performed on a homogeneous segment of the data,
      followed by a single group analysis applied to all or portions of the data using
      a robust method, insensitive to the probability distribution.

PMID- 21862599
TI  - Equivalence is victory.

PMID- 21862600
TI  - When Duzitol does not do it all: the two sides of drug synergy.

PMID- 21862601
TI  - SAMBA: moving forward.

PMID- 21862602
TI  - Low bispectral index values and death: the unresolved causality dilemma.

PMID- 21862603
TI  - Decreased nitric oxide concentration when used in conjunction with the AnaConDa
      device.

PMID- 21862604
TI  - Plagiarism and proper english writing: the dilemma.

PMID- 21862605
TI  - Measurement of dead space during anesthesia.

PMID- 21862606
TI  - Why blind nasotracheal intubation?

PMID- 21862607
TI  - Dynasthetics disclosure.

PMID- 21862608
TI  - The E3 ubiquitin ligase Mahogunin ubiquitinates the melanocortin 2 receptor.
AB  - Mahogunin ring fnger-1(MGRN1) encodes an E3 ubiquitin ligase and is mutated in
      the mahoganoid mouse. The mahoganoid mouse mutant shows similarities to the
      phenotype of another spontaneous mouse mutation known as mahogunin (mutation in
      attractin) presenting with dark coat color, spongiform neurodegeneration, and
      high embryonic lethality. It has long been hypothesized that MGRN1 may down
      regulate the function of the melanocortin 1 receptor (MC1R) via ubiquitination or
      internalization because it has been shown to possess E3 ubiquitin ligase
      activity. However, a recent study revealed that MGRN1's role in MC1R function was
      independent of receptor ubiquitination and that MGRN1 negatively regulated MC1R
      function by competing with Galphas for receptor binding. In this study we
      attempted to determine whether MGRN1 is involved in the function of the
      melanocortin 2 receptor (MC2R). We show that MGRN1 is expressed in the zona
      glomerulosa and fasciculata cells of the adrenal cortex, and in transfected human
      embryonic kidney 293 cells it colocalizes at the cell surface with the MC2R, and
      coimmunoprecipitates with the MC2R. However MGRN1 did not appear to influence the
      cAMP-signaling function of the MC2R. In the presence of MGRN1 the MC2R is
      ubiquitinated and, after ACTH stimulation, evidence of multi-monoubiquitination
      appears. It therefore seems probable that the role of MGRN1 in the adrenal
      relates to the trafficking and/or degradation of the MC2R.

PMID- 21862609
TI  - Repressor of estrogen receptor activity (REA) is essential for mammary gland
      morphogenesis and functional activities: studies in conditional knockout mice.
AB  - Estrogen receptor (ER) is a key regulator of mammary gland development and is
      also implicated in breast tumorigenesis. Because ER-mediated activities depend
      critically on coregulator partner proteins, we have investigated the consequences
      of reduction or loss of function of the coregulator repressor of ER activity
      (REA) by conditionally deleting one allele or both alleles of the REA gene at
      different stages of mammary gland development. Notably, we find that
      heterozygosity and nullizygosity for REA result in very different mammary
      phenotypes and that REA has essential roles in the distinct morphogenesis and
      functions of the mammary gland at different stages of development, pregnancy, and
      lactation. During puberty, mice homozygous null for REA in the mammary gland
      (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and
      morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed
      accelerated mammary ductal elongation, increased numbers of terminal end buds,
      and up-regulation of amphiregulin, the major paracrine mediator of estrogen
      induced ductal morphogenesis. During pregnancy and lactation, mice with
      homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein
      Cre) showed a loss of lobuloalveolar structures and increased apoptosis of
      mammary alveolar epithelium, leading to impaired milk production and significant
      reduction in growth of their offspring, whereas body weights of the offspring
      nursed by females heterozygous for REA were slightly greater than those of
      control mice. Our findings reveal that REA is essential for mammary gland
      development and has a gene dosage-dependent role in the regulation of stage
      specific physiological functions of the mammary gland.

PMID- 21862610
TI  - Maternal obesity promotes a proinflammatory signature in rat uterus and
      blastocyst.
AB  - Maternal obesity at conception increases the risk of offspring obesity, thus
      propagating an intergenerational vicious cycle. Male offspring born to obese dams
      are hyperresponsive to high fat-diets, gaining greater body weight, fat mass, and
      additional metabolic sequelae compared to lean controls. In this report, we
      identify the impact of maternal obesity before conception, on the embryo, and
      intrauterine milieu during the periimplantation period. We conducted global
      transcriptomic profiling in the uterus and periimplantation blastocyst,
      gene/protein expression analyses of inflammatory pathways in conjunction with
      endocrine and metabolic characterization in the dams at implantation. Uterine
      gene expression profiles of lean and obese dams revealed distinct signatures for
      genes regulating inflammation and lipid metabolism. Both pathway and gene-set
      enrichment analysis revealed uterine nuclear factor-kappaB and c-Jun N-terminal
      kinase signaling to be up-regulated in the uterus of obese dams, which was
      confirmed via immunoblotting. Obese uteri also evidenced an inflammatory
      secretome with higher chemokine mRNA abundance (CCL2, CCL5, CCL7, and CxCL10) and
      related regulators (TLR2, CD14, and Ccr1). Increased inflammation in the uterus
      was associated with ectopic lipid accumulation and expression of lipid metabolic
      genes. Gene expression in sex-identified male periimplantation blastocyst at day
      postcoitum 4.5 was clearly influenced by maternal obesity (359 transcripts, +/
      1.4-fold), including changes in developmental and epigenetic regulators. Akin to
      the uterus, nuclear factor-kappaB-regulated proinflammatory genes (CCL4 and CCL5)
      increased and expression of antioxidant (GPx3) and mitochondrial (TFAM and NRF1)
      genes decreased in the obese embryos. Our results suggest that ectopic lipid and
      inflammation may link maternal obesity to increased predisposition of offspring
      to obesity later in life.

PMID- 21862611
TI  - Maternal diabetes compromises the organization of hypothalamic feeding circuits
      and impairs leptin sensitivity in offspring.
AB  - Maternal diabetes is a common complication of pregnancy, and the offspring of
      diabetic mothers have a higher risk of developing obesity and type 2 diabetes
      later in life. Despite these observations, the precise biological processes
      mediating this metabolic programming are not well understood. Here, we explored
      the consequences of maternal diabetes on the organization of hypothalamic neural
      circuits involved in the regulation of energy balance. To accomplish this aim, we
      used a mouse model of maternal insulin deficiency induced by streptozotocin
      injections. Maternal diabetes was found to be associated with changes in
      offspring growth as revealed by a significantly higher pre- and postweaning body
      weight in the offspring of insulin-deficient dams relative to those of control
      mice. Mice born to diabetic dams also showed increased fasting glucose levels,
      increased insulin levels, and increased food intake during their adult lives.
      These impairments in metabolic regulation were associated with leptin resistance
      during adulthood. Importantly, the ability of leptin to activate intracellular
      signaling in arcuate neurons was also significantly reduced in neonates born to
      diabetic dams. Furthermore, neural projections from the arcuate nucleus to the
      paraventricular nucleus were markedly reduced in the offspring of insulin
      deficient dams. Together, these data show that insulin deficiency during
      gestation has long-term consequences for metabolic regulation. They also indicate
      that animals born to diabetic dams display abnormally organized hypothalamic
      feeding pathways that could result from the attenuated responsiveness of
      hypothalamic neurons to the neurotrophic actions of leptin during neonatal
      development.

PMID- 21862612
TI  - Unsaturated fatty acids stimulate LH secretion via novel PKCepsilon and -theta in
      gonadotrope cells and inhibit GnRH-induced LH release.
AB  - The activity of pituitary gonadotrope cells, crucial for reproductive function,
      is regulated by numerous factors including signals related to nutritional status.
      In this work, we demonstrated, for the first time, that in vivo central exposure
      of rats to lipids intracarotid infusion of a heparinized triglyceride emulsion
      selectively increases the expression of pituitary LH subunit genes without any
      alteration of pituitary GnRH receptor and hypothalamic GnRH or Kiss-1 transcript
      levels. Furthermore, we showed that unsaturated fatty acids (UFA), oleate and
      linoleate, increase LH release in a dose-dependent manner as well as LHbeta mRNA
      levels in both immortalized LbetaT2 gonadotrope cell line and rat primary cell
      cultures. In contrast, the saturated palmitate was ineffective. ACTH or TSH
      secretion was unaffected by UFA treatment. We demonstrated in LbetaT2 cells that
      linoleate effect is mediated neither by activation of membrane fatty acid (FA)
      receptors GPR40 or GPR120 although we characterized these receptors in LbetaT2
      cells, nor through nuclear peroxisome proliferator-activated receptors.
      Furthermore, linoleate beta-oxidation is not required for its action on LH
      secretion. In contrast, pharmacological inhibition of protein kinase C (PKC) or
      ERK pathways significantly prevented linoleate-stimulated LH release.
      Accordingly, linoleate was shown to activate novel PKC isoforms, PKCepsilon and 
      theta, as well as ERK1/2 in LbetaT2 cells. Lastly, unsaturated, but not
      saturated, FA inhibited GnRH-induced LH secretion in LbetaT2 cells as well as in
      pituitary cell cultures. Altogether, these results suggest that the pituitary is
      a relevant site of FA action and that UFA may influence reproduction by directly
      interfering with basal and GnRH-dependent gonadotrope activity.

PMID- 21862613
TI  - Elimination of the NLRP3-ASC inflammasome protects against chronic obesity
      induced pancreatic damage.
AB  - Clinical evidence that the blockade of IL-1beta in type-2 diabetic patients
      improves glycemia is indicative of an autoinflammatory mechanism that may trigger
      adiposity-driven pancreatic damage. IL-1beta is a key contributor to the obesity
      induced inflammation and subsequent insulin resistance, pancreatic beta-cell
      dysfunction, and the onset of type 2 diabetes. Our previous studies demonstrated
      that the ceramides activate the Nod-like receptor family, pyrin domain containing
      3 (Nlrp3) inflammasome to cause the generation of mature IL-1beta and ablation of
      the Nlrp3 inflammasome in diet-induced obesity improves insulin signaling.
      However, it remains unclear whether the posttranslational processing of active IL
      1beta in pancreas is regulated by the NLRP3 inflammasome or whether the alternate
      mechanisms play a dominant role in chronic obesity-induced pancreatic beta-cell
      exhaustion. Here we show that loss of ASC, a critical adaptor required for the
      assembly of the NLRP3 and absent in melanoma 2 inflammasome substantially
      improves the insulin action. Surprisingly, despite lower insulin resistance in
      the chronically obese NLRP3 and ASC knockout mice, the insulin levels were
      substantially higher when the inflammasome pathway was eliminated. The obesity
      induced increase in maturation of pancreatic IL-1beta and pancreatic islet
      fibrosis was dependent on the NLRP3 inflammasome activation. Furthermore,
      elimination of NLRP3 inflammasome protected the pancreatic beta-cells from cell
      death caused by long-term high-fat feeding during obesity with significant
      increase in the size of the islets of Langerhans. Collectively, this study
      provides direct in vivo evidence that activation of the NLRP3 inflammasome in
      diet-induced obesity is a critical trigger in causing pancreatic damage and is an
      important mechanism of progression toward type 2 diabetes.

PMID- 21862614
TI  - Characterization of novel RFamide peptides in the central nervous system of the
      brown hagfish: isolation, localization, and functional analysis.
AB  - RFamide (RFa) peptides play various important roles in the central nervous system
      in both invertebrates and vertebrates. However, there is no evidence of the
      existence of any RFamide peptide in the brain of hagfish, one of the oldest
      lineages of vertebrates. In this study, we sought to identify novel RFamide
      peptides from the brains of hagfish (Paramyxine atami). We identified four novel
      RFamide peptides, which had the C-terminal Pro-Gln-Arg-Phe-NH2 structure. cDNA
      cloning revealed that the identified RFamide peptides are encoded in two types of
      cDNA. Molecular phylogenetic analysis of the two precursors indicated that the
      hagfish RFamide peptides belong to the PQRFamide peptide group that includes
      mammalian neuropeptide FF and AF. Based on immunohistochemistry and in situ
      hybridization, hagfish PQRFamide peptide precursor mRNA and its translated
      peptides were localized in the infundibular nucleus of the hypothalamus.
      Immunoreactive fibers were terminated on blood vessels in the infundibular
      nucleus. Dense immunoreactive fibers were also observed in other brain regions.
      We further showed that one of the hagfish PQRFamide peptides significantly
      stimulated the expression of gonadotropin-beta mRNA in the cultured hagfish
      pituitary. These results indicate that the control mechanism of gonadotropin
      expression by a hypothalamic neuropeptide evolved in the agnathan brain. This is
      the first evidence describing the identification of RFamide peptides in the
      hagfish brain. This is also the first report showing the regulation of
      gonadotropin expression by a homolog of neuropeptide FF that belongs to the
      PQRFamide peptide group in any vertebrate.

PMID- 21862617
TI  - Induction of autoimmune thyroiditis by depletion of CD4+CD25+ regulatory T cells
      in thyroiditis-resistant IL-17, but not interferon-gamma receptor, knockout
      nonobese diabetic-H2h4 mice.
AB  - Iodine-induced experimental autoimmune thyroiditis in the nonobese diabetic (NOD)
      H2h4 mouse is a prototype of animal models of Hashimoto's thyroiditis in humans.
      Recent studies have shown the resistance to thyroiditis of NOD-H2h4 mice
      genetically deficient for either IL-17 or interferon (IFN)-gamma, implicating
      both of T helper type 1 (Th1) and Th17 immune responses in disease pathogenesis.
      However, we hypothesized that robust induction of a single arm of effector T
      cells (either Th1 or Th17) might be sufficient for inducing thyroiditis in NOD
      H2h4 mice. To address this hypothesis, enhanced immune responses consisting of
      either Th1 or Th17 were induced by anti-CD25 antibody-mediated depletion of
      regulatory T cells (Treg) in thyroiditis-resistant IL-17 knockout (KO) or IFN
      gamma receptor (IFN-gammaR) KO, respectively, NOD-H2h4 mice. Depletion of Treg in
      IL-17 KO mice (i.e. Th1 enhancement) elicited antithyroglobulin autoantibodies
      and thyroiditis. Immunohistochemical analysis of the thyroid glands revealed the
      similar intrathyroidal lymphocyte infiltration patterns, with CD4+ T and CD19+ B
      cells being dominant between the wild-type and Treg-depleted IL-17 KO mice. In
      contrast, Treg-depleted IFN-gammaR KO mice remained thyroiditis resistant.
      Intracellular cytokine staining assays showed differentiation of Th1 cells in IL
      17 KO mice but not of Th17 cells in IFN-gammaR KO mice. Our findings demonstrate
      that a robust Th1 immune response can by itself induce thyroiditis in otherwise
      thyroiditis-resistant IL-17 KO mice. Thus, unlike Th17 cells in IFN-gammaR KO
      mice, Th1 cells enhanced by Treg depletion can be sustained and induce
      thyroiditis.

PMID- 21862616
TI  - The Ca2+/calmodulin-dependent protein kinase kinase, CaMKK2, inhibits
      preadipocyte differentiation.
AB  - When fed a standard chow diet, CaMKK2 null mice have increased adiposity and
      larger adipocytes than do wild-type mice, whereas energy balance is unchanged.
      Here, we show that Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2)
      is expressed in preadipocytes, where it functions as an AMP-activated protein
      kinase (AMPK)alpha kinase. Acute inhibition or deletion of CaMKK2 in
      preadipocytes enhances their differentiation into mature adipocytes, which can be
      reversed by 5-aminoimidazole-4-carboxamide ribonucleotide-mediated activation of
      AMPK. During adipogenesis, CaMKK2 expression is markedly decreased and temporally
      accompanied by increases in mRNA encoding the early adipogenic genes
      CCAAT/enhancer binding protein (C/EBP) beta and C/EBP delta. Preadipocyte factor
      1 has been reported to inhibit adipogenesis by up-regulating sex determining
      region Y-box 9 (Sox9) expression in preadipocytes and Sox9 suppresses C/EBPbeta
      and C/EBPdelta transcription. We show that inhibition of the CaMKK2/AMPK
      signaling cascade in preadipocytes reduces preadipocyte factor 1 and Sox9 mRNA
      resulting in accelerated adipogenesis. We conclude that CaMKK2 and AMPK function
      in a signaling pathway that participates in the regulation of adiposity.

PMID- 21862615
TI  - Insulin/IGF-I regulation of necdin and brown adipocyte differentiation via CREB-
      and FoxO1-associated pathways.
AB  - Brown adipose tissue plays an important role in obesity, insulin resistance, and
      diabetes. We have previously shown that the transition from brown preadipocytes
      to mature adipocytes is mediated in part by insulin receptor substrate (IRS)-1
      and the cell cycle regulator protein necdin. In this study, we used
      pharmacological inhibitors and adenoviral dominant negative constructs to
      demonstrate that this transition involves IRS-1 activation of Ras and ERK1/2,
      resulting in phosphorylation of cAMP response element-binding protein (CREB) and
      suppression of necdin expression. This signaling did not include an elevation of
      intracellular calcium. A constitutively active form of CREB expressed in IRS-1
      knockout cells decreased necdin promoter activity, necdin mRNA, and necdin
      protein levels, leading to a partial restoration of differentiation. By contrast,
      forkhead box protein (Fox)O1, which is regulated by the phosphoinositide 3 kinase
      Akt pathway, increased necdin promoter activity. Based on reporter gene assays
      using truncations of the necdin promoter and chromatin immunoprecipitation
      studies, we demonstrated that CREB and FoxO1 are recruited to the necdin
      promoter, likely interacting with specific consensus sequences in the proximal
      region. Based on these results, we propose that insulin/IGF-I act through IRS-1
      phosphorylation to stimulate differentiation of brown preadipocytes via two
      complementary pathways: 1) the Ras-ERK1/2 pathway to activate CREB and 2) the
      phosphoinositide 3 kinase-Akt pathway to deactivate FoxO1. These two pathways
      combine to decrease necdin levels and permit the clonal expansion and coordinated
      gene expression necessary to complete brown adipocyte differentiation.

PMID- 21862618
TI  - Minireview: nesfatin-1--an emerging new player in the brain-gut, endocrine, and
      metabolic axis.
AB  - Nesfatin-1 is a recently identified 82-amino-acid peptide derived from the
      precursor protein, nucleobindin2 (NUCB2). The brain distribution of
      NUCB2/nesfatin-1 at the mRNA and protein level along with functional studies in
      rodents support a role for NUCB2/nesfatin-1 as a novel satiety molecule acting
      through leptin-independent mechanisms. In addition, nesfatin-1 induces a wide
      spectrum of central actions to stimulate the pituitary-adrenal axis and
      sympathetic nervous system and influences visceral functions and emotion. These
      central actions combined with the activation of NUCB2/nesfatin-1 neurons in the
      brain by various stressors are indicative of a role in the adaptive response
      under stressful conditions. In the periphery, evidence is mounting that nesfatin
      1 exerts a direct glucose-dependent insulinotropic action on beta-cells of the
      pancreatic islets. However, the cellular mechanisms of nesfatin-1's action remain
      poorly understood, partly because the receptor through which nesfatin-1 exerts
      its pleiotropic actions is yet to be identified.

PMID- 21862619
TI  - From pituitary expansion to empty sella: disease progression in a mouse model of
      autoimmune hypophysitis.
AB  - Lymphocytic hypophysitis has a variable clinical course, where a swelling of the
      pituitary gland at presentation is thought to be followed by pituitary atrophy
      and empty sella. Data in patients, however, are scanty and contradictory. To
      better define the course of hypophysitis, we used an experimental model based on
      the injection of pituitary proteins into SJL mice. A cohort of 33 mice was
      divided into three groups: 18 cases were immunized with pituitary proteins
      emulsified in complete Freund's adjuvant; six controls were injected with
      adjuvant only; and nine controls were left untreated. Mice were followed by
      cranial magnetic resonance imaging (MRI) for up to 300 d, for a total of 106 MRI
      scans, and killed at different time points to correlate radiological and
      pathological findings. Empty sella was defined as a reduction in pituitary volume
      greater than 2 sd below the mean volume. All immunized mice showed by MRI a
      significant expansion of pituitary volume during the early phases of the disease.
      The volume then decreased gradually in the majority of cases (14 of 18, 78%),
      reaching empty sella values by d 300 after immunization. In a minority of cases
      (four of 18, 22%), the decrease was so rapid and marked to induce a central area
      of necrosis accompanied by hemorrhages, mimicking the condition known in patients
      as pituitary apoplexy. No radiological or pathological changes were observed in
      controls. Overall, these findings indicate that the evolution of hypophysitis is
      complex but can lead, through different routes, to the development of empty
      sella.

PMID- 21862620
TI  - Study of the potential association of adipose tissue GLP-1 receptor with obesity
      and insulin resistance.
AB  - The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful
      therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of
      GLP-1 on beta-cells and the nervous and digestive systems are well known. The
      action of this peptide in adipose tissue (AT), however, is still poorly defined.
      Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R)
      in AT and obesity and insulin resistance (IR). We provide evidence for the
      presence of this receptor in AT and show that its mRNA and protein expressions
      are increased in visceral adipose depots from morbidly obese patients with a high
      degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and
      lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in
      3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate
      cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP
      1R in AT correlated positively with the homeostasis model assessment index in
      obese IR subjects. Furthermore, prospective studies carried out with patients
      that underwent biliopancreatic diversion surgery showed that subjects with high
      levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this
      tissue, were those whose insulin sensitivity improved after surgery, suggesting
      the potential relationship between AT GLP-1R and insulin sensitivity amelioration
      in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system
      in AT represents another potential candidate for improving insulin sensitivity in
      obese patients.

PMID- 21862621
TI  - Mutant Forkhead L2 (FOXL2) proteins associated with premature ovarian failure
      (POF) dimerize with wild-type FOXL2, leading to altered regulation of genes
      associated with granulosa cell differentiation.
AB  - Premature ovarian failure in the autosomal dominant disorder blepharophimosis
      ptosis-epicanthus inversus is due to mutations in the gene encoding Forkhead L2
      (FOXL2), producing putative truncated proteins. We previously demonstrated that
      FOXL2 is a transcriptional repressor of the steroidogenic acute regulatory
      (StAR), P450SCC (CYP11A), P450aromatase (CYP19), and cyclin D2 (CCND2) genes,
      markers of ovarian follicle proliferation and differentiation. Furthermore, we
      found that mutations of FOXL2 may regulate wild-type FOXL2, leading to loss of
      transcriptional repression of CYP19, similar to StAR. However, the regulatory
      mechanisms underlying these premature ovarian failure-associated mutations remain
      largely unknown. Therefore, we examined the effects of a FOXL2 mutant protein on
      the transcriptional repression of the CYP19 promoter by the full-length protein.
      We found that mutant FOXL2 exerts a dominant-negative effect on the repression of
      CYP19 by wild-type FOXL2. Both wild-type and mutant FOXL2 and can form homo- and
      heterodimers. We identified a minimal -57-bp human CYP19 promoter containing two
      potential FOXL2-binding regions and found that both wild-type and mutant FOXL2
      can bind to either of these regions. Mutational analysis revealed that either
      site is sufficient for transcriptional repression by wild-type FOXL2, and the
      dominant-negative effect of mutant FOXL2, but these are eliminated when both
      sites are mutated. These findings confirm that mutant FOXL2 exerts a dominant
      negative effect on wild-type FOXL2's activity as a transcriptional repressor of
      key genes in ovarian follicle differentiation and suggest that this is likely due
      to heterodimer formation and possibly also competition for DNA binding.

PMID- 21862622
TI  - The angiostatic protein 16K human prolactin significantly prevents tumor-induced
      lymphangiogenesis by affecting lymphatic endothelial cells.
AB  - The 16-kDa angiostatic N-terminal fragment of human prolactin (16K hPRL) has been
      reported to be a new potent anticancer compound. This protein has already proven
      its efficiency in several mouse tumor models in which it prevented tumor-induced
      angiogenesis and delayed tumor growth. In addition to angiogenesis, tumors also
      stimulate the formation of lymphatic vessels, which contribute to tumor cell
      dissemination and metastasis. However, the role of 16K hPRL in tumor-induced
      lymphangiogenesis has never been investigated. We establish in vitro that 16K
      hPRL induces apoptosis and inhibits proliferation, migration, and tube formation
      of human dermal lymphatic microvascular endothelial cells. In addition, in a
      B16F10 melanoma mouse model, we found a decreased number of lymphatic vessels in
      the primary tumor and in the sentinel lymph nodes after 16K hPRL treatment. This
      decrease is accompanied by a significant diminished expression of lymphangiogenic
      markers in primary tumors and sentinel lymph nodes as determined by quantitative
      RT-PCR. These results suggest, for the first time, that 16K hPRL is a
      lymphangiostatic as well as an angiostatic agent with antitumor properties.

PMID- 21862623
TI  - The inflammasome and caspase-1 activation: a new mechanism underlying increased
      inflammatory activity in human visceral adipose tissue.
AB  - The immune competent abdominal adipose tissue, either stored viscerally [visceral
      adipose tissue (VAT)] or sc [sc adipose tissue (SAT)], has been identified as a
      source of IL-1beta and IL-18. To become active, the proforms of these cytokines
      require processing by caspase-1, which itself is mediated by the inflammasome. In
      this descriptive study, we investigate the expression of inflammasome components
      and caspase-1 in human fat and determine whether caspase-1 activity contributes
      to the enhanced inflammatory status of VAT. Paired SAT and VAT biopsies from 10
      overweight subjects (body mass index, 25-28 kg/m(2)) were used to study the
      cellular composition and the intrinsic inflammatory capacity of both adipose
      tissue depots. The percentage of CD8(+) T cells within the lymphocyte fraction
      was significantly higher in VAT compared with SAT (41.6 vs. 30.4%; P < 0.05).
      Adipose tissue cultures showed a higher release of IL-1beta (10-fold; P < 0.05),
      IL-18 (3-fold; P < 0.05), and IL-6 and IL-8 (3-fold, P < 0.05; and 4-fold, P <
      0.05, respectively) from VAT compared with SAT that was significantly reduced by
      inhibiting caspase-1 activity. In addition, caspase-1 activity was 3-fold (P <
      0.05) higher in VAT compared with SAT, together with an increase in the protein
      levels of the inflammasome members apoptosis-associated speck-like protein
      containing a C-terminal caspase-recruitment domain (2-fold; P < 0.05) and
      nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3
      (2-fold; nonsignificant). Finally, caspase-1 activity levels were positively
      correlated with the percentage of CD8(+) T cells present in adipose tissue. Our
      results show that caspase-1 and nucleotide-binding oligomerization domain-like
      receptor pyrin domain containing 3 inflammasome members are abundantly present in
      human VAT. The increased intrinsic caspase-1 activity in VAT represents a novel
      and specific inflammatory pathway that may determine the proinflammatory
      character of this specific depot.

PMID- 21862624
TI  - Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung
      cancer in EPIC.
AB  - BACKGROUNDS: Multiple polymorphisms affecting smoking behavior have been
      identified through genome-wide association studies. Circulating levels of the
      nicotine metabolite cotinine is a marker of recent smoking exposure. Hence,
      genetic variants influencing smoking behavior are expected to be associated with
      cotinine levels. METHODS: We conducted an analysis in a lung cancer case-control
      study nested within the European Prospective Investigation into Cancer and
      Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide
      polymorphisms (SNP) previously associated with smoking behavior on (i)
      circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805
      controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14,
      8p11, 10q23, 15q25, and 19q13. RESULTS: Two variants in the nicotinic
      acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and
      rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in
      current smokers and with lung cancer risk (P < 0.001 and P = 0.001,
      respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with
      increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung
      cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14,
      8p11, and 10q23 were not associated with cotinine or lung cancer risk.
      CONCLUSIONS: 15q25 and 19q13 SNPs were associated with circulating cotinine. The
      directions of association for 15q25 variants with cotinine were in accordance
      with that expected of lung cancer risk, whereas SNPs on 19q13 displayed
      contrasting associations of cotinine and lung cancer that require further
      investigation. IMPACT: This study is the largest to date investigating the
      effects of polymorphisms affecting smoking behavior on lung cancer risk using
      circulating cotinine measures as proxies for recent smoking behavior.

PMID- 21862625
TI  - Genome-based analysis of the nonhuman primate Macaca fascicularis as a model for
      drug safety assessment.
AB  - The long-tailed macaque, also referred to as cynomolgus monkey (Macaca
      fascicularis), is one of the most important nonhuman primate animal models in
      basic and applied biomedical research. To improve the predictive power of primate
      experiments for humans, we determined the genome sequence of a Macaca
      fascicularis female of Mauritian origin using a whole-genome shotgun sequencing
      approach. We applied a template switch strategy that uses either the rhesus or
      the human genome to assemble sequence reads. The sixfold sequence coverage of the
      draft genome sequence enabled discovery of about 2.1 million potential single
      nucleotide polymorphisms based on occurrence of a dimorphic nucleotide at a given
      position in the genome sequence. Homology-based annotation allowed us to identify
      17,387 orthologs of human protein-coding genes in the M. fascicularis draft
      genome, and the predicted transcripts enabled the design of a M. fascicularis
      specific gene expression microarray. Using liver samples from 36 individuals of
      different geographic origin we identified 718 genes with highly variable
      expression in liver, whereas the majority of the transcriptome shows relatively
      stable and comparable expression. Knowledge of the M. fascicularis draft genome
      is an important contribution to both the use of this animal in disease models and
      the safety assessment of drugs and their metabolites. In particular, this
      information allows high-resolution genotyping and microarray-based gene
      expression profiling for animal stratification, thereby allowing the use of well
      characterized animals for safety testing. Finally, the genome sequence presented
      here is a significant contribution to the global "3R" animal welfare initiative,
      which has the goal to reduce, refine, and replace animal experiments.

PMID- 21862626
TI  - DNA methylation profiles of human active and inactive X chromosomes.
AB  - X-chromosome inactivation (XCI) is a dosage compensation mechanism that silences
      the majority of genes on one X chromosome in each female cell. To characterize
      epigenetic changes that accompany this process, we measured DNA methylation
      levels in 45,X patients carrying a single active X chromosome (X(a)), and in
      normal females, who carry one X(a) and one inactive X (X(i)). Methylated DNA was
      immunoprecipitated and hybridized to high-density oligonucleotide arrays covering
      the X chromosome, generating epigenetic profiles of active and inactive X
      chromosomes. We observed that XCI is accompanied by changes in DNA methylation
      specifically at CpG islands (CGIs). While the majority of CGIs show increased
      methylation levels on the X(i), XCI actually results in significant reductions in
      methylation at 7% of CGIs. Both intra- and inter-genic CGIs undergo epigenetic
      modification, with the biggest increase in methylation occurring at the promoters
      of genes silenced by XCI. In contrast, genes escaping XCI generally have low
      levels of promoter methylation, while genes that show inter-individual variation
      in silencing show intermediate increases in methylation. Thus, promoter
      methylation and susceptibility to XCI are correlated. We also observed a global
      correlation between CGI methylation and the evolutionary age of X-chromosome
      strata, and that genes escaping XCI show increased methylation within gene
      bodies. We used our epigenetic map to predict 26 novel genes escaping XCI, and
      searched for parent-of-origin-specific methylation differences, but found no
      evidence to support imprinting on the human X chromosome. Our study provides a
      detailed analysis of the epigenetic profile of active and inactive X chromosomes.

PMID- 21862627
TI  - Relating CNVs to transcriptome data at fine resolution: assessment of the effect
      of variant size, type, and overlap with functional regions.
AB  - Copy-number variants (CNVs) form an abundant class of genetic variation with a
      presumed widespread impact on individual traits. While recent advances, such as
      the population-scale sequencing of human genomes, facilitated the fine-scale
      mapping of CNVs, the phenotypic impact of most of these CNVs remains unclear. By
      relating copy-number genotypes to transcriptome sequencing data, we have
      evaluated the impact of CNVs, mapped at fine scale, on gene expression. Based on
      data from 129 individuals with ancestry from two populations, we identified CNVs
      associated with the expression of 110 genes, with 13% of the associations
      involving complex, multiallelic CNVs. Categorization of CNVs according to variant
      type, size, and gene overlap enabled us to examine the impact of different CNV
      classes on expression variation. While many small (<4 kb) CNVs were associated
      with expression variation, overall we observed an enrichment of large
      duplications and deletions, including large intergenic CNVs, relative to the
      entire set of expression-associated CNVs. Furthermore, the copy number of genes
      intersecting with CNVs typically correlated positively with the genes'
      expression, and also was more strongly correlated with expression than nearby
      single nucleotide polymorphisms, suggesting a frequent causal role of CNVs in
      expression quantitative trait loci (eQTLs). We also elucidated unexpected cases
      of negative correlations between copy number and expression by assessing the
      CNVs' effects on the structure and regulation of genes. Finally, we examined
      dosage compensation of transcript levels. Our results suggest that association
      studies can gain in resolution and power by including fine-scale CNV information,
      such as those obtained from population-scale sequencing.

PMID- 21862628
TI  - Dot/Icm type IVB secretion system requirements for Coxiella burnetii growth in
      human macrophages.
AB  - Central to Q fever pathogenesis is replication of the causative agent, Coxiella
      burnetii, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear
      phagocytes. C. burnetii modulates PV biogenesis and other host cell functions,
      such as apoptotic signaling, presumably via the activity of proteins delivered to
      the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study,
      we utilized a C. burnetii strain carrying IcmD inactivated by the Himar1
      transposon to investigate the requirements for Dot/Icm function in C. burnetii
      parasitism of human THP-1 macrophage-like cells. The icmD::Tn mutant failed to
      secrete characterized T4BSS substrates, a defect that correlated with deficient
      replication, PV development, and apoptosis protection. Restoration of type IVB
      secretion and intracellular growth of the icmD::Tn mutant required
      complementation with icmD, -J, and -B, indicating a polar effect of the
      transposon insertion on downstream dot/icm genes. Induction of icmDJB expression
      at 1 day postinfection resulted in C. burnetii replication and PV generation.
      Collectively, these data prove that T4BSS function is required for productive
      infection of human macrophages by C. burnetii. However, illustrating the
      metabolic flexibility of C. burnetti, the icmD::Tn mutant could replicate
      intracellularly when sequestered in a PV generated by wild-type bacteria, where
      Dot/Icm function is provided in trans, and within a phenotypically similar PV
      generated by the protozoan parasite Leishmania amazonensis, where host cells are
      devoid of Dot/Icm T4BSS effector proteins.

PMID- 21862630
TI  - Population genetics of Vibrio cholerae from Nepal in 2010: evidence on the origin
      of the Haitian outbreak.
AB  - Cholera continues to be an important cause of human infections, and outbreaks are
      often observed after natural disasters, such as the one following the 2010
      earthquake in Haiti. Once the cholera outbreak was confirmed, rumors spread that
      the disease was brought to Haiti by a battalion of Nepalese soldiers serving as
      United Nations peacekeepers. This possible connection has never been confirmed.
      We used whole-genome sequence typing (WGST), pulsed-field gel electrophoresis
      (PFGE), and antimicrobial susceptibility testing to characterize 24 recent Vibrio
      cholerae isolates from Nepal and evaluate the suggested epidemiological link with
      the Haitian outbreak. The isolates were obtained from 30 July to 1 November 2010
      from five different districts in Nepal. We compared the 24 genomes to 10
      previously sequenced V. cholerae isolates, including 3 from the Haitian outbreak
      (began July 2010). Antimicrobial susceptibility and PFGE patterns were consistent
      with an epidemiological link between the isolates from Nepal and Haiti. WGST
      showed that all 24 V. cholerae isolates from Nepal belonged to a single
      monophyletic group that also contained isolates from Bangladesh and Haiti. The
      Nepalese isolates were divided into four closely related clusters. One cluster
      contained three Nepalese isolates and three Haitian isolates that were almost
      identical, with only 1- or 2-bp differences. Results in this study are consistent
      with Nepal as the origin of the Haitian outbreak. This highlights how rapidly
      infectious diseases might be transmitted globally through international travel
      and how public health officials need advanced molecular tools along with standard
      epidemiological analyses to quickly determine the sources of outbreaks.

PMID- 21862629
TI  - Potential for direct interspecies electron transfer in methanogenic wastewater
      digester aggregates.
AB  - Mechanisms for electron transfer within microbial aggregates derived from an
      upflow anaerobic sludge blanket reactor converting brewery waste to methane were
      investigated in order to better understand the function of methanogenic
      consortia. The aggregates were electrically conductive, with conductivities 3
      fold higher than the conductivities previously reported for dual-species
      aggregates of Geobacter species in which the two species appeared to exchange
      electrons via interspecies electron transfer. The temperature dependence response
      of the aggregate conductance was characteristic of the organic metallic-like
      conductance previously described for the conductive pili of Geobacter
      sulfurreducens and was inconsistent with electron conduction through minerals.
      Studies in which aggregates were incubated with high concentrations of potential
      electron donors demonstrated that the aggregates had no significant capacity for
      conversion of hydrogen to methane. The aggregates converted formate to methane
      but at rates too low to account for the rates at which that the aggregates
      syntrophically metabolized ethanol, an important component of the reactor
      influent. Geobacter species comprised 25% of 16S rRNA gene sequences recovered
      from the aggregates, suggesting that Geobacter species may have contributed to
      some but probably not all of the aggregate conductivity. Microorganisms most
      closely related to the acetate-utilizing Methanosaeta concilii accounted for more
      than 90% of the sequences that could be assigned to methane producers, consistent
      with the poor capacity for hydrogen and formate utilization. These results
      demonstrate for the first time that methanogenic wastewater aggregates can be
      electrically conductive and suggest that direct interspecies electron transfer
      could be an important mechanism for electron exchange in some methanogenic
      systems.

PMID- 21862631
TI  - TGF-beta/SMAD/GLI2 signaling axis in cancer progression and metastasis.
AB  - The Hedgehog (HH) and TGF-beta signaling pathways represent essential regulators
      of cell proliferation and differentiation during embryogenesis. Pathway
      deregulation is a characteristic of various cancers. Recently, evidence for a
      convergence of these pathways at the level of the GLI2 transcription factor in
      the context of tumor initiation and progression to metastasis has emerged. This
      short review summarizes recent knowledge about GLI2 function and mechanisms of
      action downstream of TGF-beta in cancer.

PMID- 21862632
TI  - Novel cryo-imaging of the glioma tumor microenvironment reveals migration and
      dispersal pathways in vivid three-dimensional detail.
AB  - Traditional methods of imaging cell migration in the tumor microenvironment
      include serial sections of xenografts and standard histologic stains. Current
      molecular imaging techniques suffer from low resolution and difficulty in imaging
      through the skull. Here we show how computer algorithms can be used to
      reconstruct images from tissue sections obtained from mouse xenograft models of
      human glioma and can be rendered into three-dimensional images offering exquisite
      anatomic detail of tumor cell dispersal. Our findings identify human LN-229 and
      rodent CNS-1 glioma cells as valid systems to study the highly dispersive nature
      of glioma tumor cells along blood vessels and white matter tracts in vivo. This
      novel cryo-imaging technique provides a valuable tool to evaluate therapeutic
      interventions targeted at limiting tumor cell invasion and dispersal.

PMID- 21862633
TI  - Estrogen-dependent gene transcription in human breast cancer cells relies upon
      proteasome-dependent monoubiquitination of histone H2B.
AB  - The estrogen receptor-alpha (ERalpha) determines the phenotype of breast cancers
      where it serves as a positive prognostic indicator. ERalpha is a well-established
      target for breast cancer therapy, but strategies to target its function remain of
      interest to address therapeutic resistance and further improve treatment. Recent
      findings indicate that proteasome inhibition can regulate estrogen-induced
      transcription, but how ERalpha function might be regulated was uncertain. In this
      study, we investigated the transcriptome-wide effects of the proteasome inhibitor
      bortezomib on estrogen-regulated transcription in MCF7 human breast cancer cells
      and showed that bortezomib caused a specific global decrease in estrogen-induced
      gene expression. This effect was specific because gene expression induced by the
      glucocorticoid receptor was unaffected by bortezomib. Surprisingly, we observed
      no changes in ERalpha recruitment or assembly of its transcriptional activation
      complex on ERalpha target genes. Instead, we found that proteasome inhibition
      caused a global decrease in histone H2B monoubiquitination (H2Bub1), leading to
      transcriptional elongation defects on estrogen target genes and to decreased
      chromatin dynamics overall. In confirming the functional significance of this
      link, we showed that RNA interference-mediated knockdown of the H2B ubiquitin
      ligase RNF40 decreased ERalpha-induced gene transcription. Surprisingly, RNF40
      knockdown also supported estrogen-independent cell proliferation and activation
      of cell survival signaling pathways. Most importantly, we found that H2Bub1
      levels decrease during tumor progression. H2Bub1 was abundant in normal mammary
      epithelium and benign breast tumors but absent in most malignant and metastatic
      breast cancers. Taken together, our findings show how ERalpha activity is blunted
      by bortezomib treatment as a result of reducing the downstream ubiquitin
      dependent function of H2Bub1. In supporting a tumor suppressor role for H2Bub1 in
      breast cancer, our findings offer a rational basis to pursue H2Bub1-based
      therapies for future management of breast cancer.

PMID- 21862634
TI  - Nano in cancer: linking chemistry, biology, and clinical applications in vivo.
AB  - Development of nanoparticle agents for cancer therapeutics and diagnostics is
      steadily progressing and was the subject of the inaugural conference entitled,
      "Nano in Cancer," held during January 12-15, 2011, in Miami, FL. The meeting
      program was developed by co-chairs David Piwnica-Worms (Washington University in
      St. Louis), Jan Schnitzer (Proteogenomics Research Institute for Systems
      Medicine, San Diego), and Karen Wooley (Texas A&M University). Topics discussed
      for nanoparticle platforms under development included: nanotechnologies for
      cancer diagnostics and imaging, overcoming in vivo barriers, therapeutic
      nanoparticles and clinical prospects, and safety issues for nanotechnologies. Two
      important concepts emerged from this meeting. The first was the urgent need for
      uniform standards and protocols for nanoparticle characterization in vitro and in
      vivo, and the second was the continued need for discovery of definitive targets
      for tumor-directed nanoparticles across various cancers.

PMID- 21862635
TI  - Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and
      is associated with poor prognosis in colorectal cancers.
AB  - The functional impact of recently discovered long noncoding RNAs (ncRNAs) in
      human cancer remains to be clarified. One long ncRNA which has attracted
      attention is the Hox transcript antisense intergenic RNA termed HOTAIR, a long
      ncRNA expressed from the developmental HOXC locus located on chromosome 12q13.13.
      In cooperation with Polycomb complex PRC2, the HOTAIR long ncRNA is reported to
      reprogram chromatin organization and promote breast cancer metastasis. In this
      study, we examined the status and function of HOTAIR in patients with stage IV
      colorectal cancer (CRC) who have liver metastases and a poor prognosis. HOTAIR
      expression levels were higher in cancerous tissues than in corresponding
      noncancerous tissues and high HOTAIR expression correlated tightly with the
      presence of liver metastasis. Moreover, patients with high HOTAIR expression had
      a relatively poorer prognosis. In a subset of 32 CRC specimens, gene set
      enrichment analysis using cDNA array data revealed a close correlation between
      expression of HOTAIR and members of the PRC2 complex (SUZ12, EZH2, and H3K27me3).
      Our findings suggest that HOTAIR expression is associated with a genome-wide
      reprogramming of PRC2 function not only in breast cancer but also in CRC, where
      upregulation of this long ncRNA may be a critical element in metastatic
      progression.

PMID- 21862637
TI  - Therapeutic oligonucleotides: the road not taken.
AB  - Antisense oligonucleotide therapeutics have been in development for almost 25
      years without a single U.S. Food and Drug Administration-approved product in
      cancer. The reasons for this absence stem, in part, from a deep lack of
      understanding about how to deliver these molecules to cancer cells in vivo.

PMID- 21862636
TI  - p38gamma promotes breast cancer cell motility and metastasis through regulation
      of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior.
AB  - Understanding the molecular alterations that confer cancer cells with motile,
      metastatic properties is needed to improve patient survival. Here, we report that
      p38gamma motogen-activated protein kinase regulates breast cancer cell motility
      and metastasis, in part, by controlling expression of the metastasis-associated
      small GTPase RhoC. This p38gamma-RhoC regulatory connection was mediated by a
      novel mechanism of modulating RhoC ubiquitination. This relationship persisted
      across multiple cell lines and in clinical breast cancer specimens. Using a
      computational mechanical model based on the finite element method, we showed that
      p38gamma-mediated cytoskeletal changes are sufficient to control cell motility.
      This model predicted novel dynamics of leading edge actin protrusions, which were
      experimentally verified and established to be closely related to cell shape and
      cytoskeletal morphology. Clinical relevance was supported by evidence that
      elevated expression of p38gamma is associated with lower overall survival of
      patients with breast cancer. Taken together, our results offer a detailed
      characterization of how p38gamma contributes to breast cancer progression. Herein
      we present a new mechanics-based analysis of cell motility, and report on the
      discovery of a leading edge behavior in motile cells to accommodate modified
      cytoskeletal architecture. In summary, these findings not only identify a novel
      mechanism for regulating RhoC expression but also advance p38gamma as a candidate
      therapeutic target.

PMID- 21862639
TI  - Exploring the roles of saturating and supersaturating contrast-response functions
      in conjunction detection and contrast coding.
AB  - J. W. Peirce (2007, p. 1) has proposed that saturating contrast-response
      functions in V1 and V2 may form "a critical part of the selective detection of
      compound stimuli over their components" and that supersaturating (non-monotonic)
      functions allow even greater conjunction selectivity. Here, we argue that
      saturating and supersaturating contrast-response functions cannot be exploited by
      conjunction detectors in the way that Peirce proposes. First, the advantage of
      these functions only applies to conjunctions with components of lower contrast
      than the equivalent non-conjunction stimulus, e.g., plaids (conjunctions) vs.
      gratings (non-conjunctions); most types of conjunction do not have this property.
      Second, in many experiments, conjunction and non-conjunction components have
      identical contrast, sampling the contrast-response function at a single point, so
      the function's shape is irrelevant. Third, Peirce considered only maximum
      contrast stimuli, whereas contrasts in natural scenes are low, corresponding to a
      contrast-response function's expansive region; we show that, for naturally
      occurring contrasts, Peirce's plaid detector would generally respond more weakly
      to plaids than to gratings. We also reassess Peirce's claim that supersaturating
      contrast-response functions are suboptimal for contrast coding; we argue that
      supersaturation improves contrast coding, and that the multiplicity of
      supersaturation levels reflects varying trade-offs between contrast coding and
      coding of other features.

PMID- 21862638
TI  - Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces
      cerevisiae.
AB  - Production of messenger ribonucleoprotein particles (mRNPs) is subjected to
      quality control (QC). In Saccharomyces cerevisiae, the RNA exosome and its
      cofactors are part of the nuclear QC machinery that removes, or stalls, aberrant
      molecules, thereby ensuring that only correctly formed mRNPs are exported to the
      cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae
      cytoplasmic deadenylase, has recently been implied in nuclear exosome-related
      processes. Consistent with a possible nuclear function of the complex, the
      deletion or mutation of Ccr4-Not factors also elicits transcription phenotypes.
      Here we use genetic depletion of the Mft1p protein of the THO transcription/mRNP
      packaging complex as a model system to link the Ccr4-Not complex to nuclear mRNP
      QC. We reveal strong genetic interactions between alleles of the Ccr4-Not complex
      with both the exosomal RRP6 and MFT1 genes. Moreover, Rrp6p-dependent in vivo QC
      phenotypes of Deltamft1 cells can be rescued by codeletion of several Ccr4-Not
      components. We discuss how the Ccr4-Not complex may connect with the mRNP QC
      pathway.

PMID- 21862640
TI  - Efficacy of a computerized optokinetic nystagmus test in prediction of visual
      acuity of better than 20/200.
AB  - PURPOSE: To evaluate the efficacy of a computerized optokinetic nystagmus (OKN)
      test in detecting visual acuity (VA) of >20/200. METHODS: This was a combined
      retrospective and prospective, noninterventional study. In phase I of the study,
      data from 168 eyes of 154 subjects who underwent the computerized objective VA
      test using OKN responses at Seoul National University Bundang Hospital were
      reviewed and reanalyzed, and a table for predicting the range of subjective VA
      for each step of objective VA was made. From the table, the cutoff value for
      detecting VA of >20/200 was determined. In phase II of the study, the
      distribution of subjective VA according to each objective VA step was determined
      for 80 eyes of 40 subjects at Seoul Veteran's Hospital. The sensitivity and the
      specificity of our cutoff value were evaluated in the two groups. RESULTS: No
      significant difference was found in the distribution of subjective VA according
      to objective VA steps between the two groups. For the subjects in phase I of the
      study, the sensitivity of our cutoff value was 91.7% and the specificity was
      88.3%. For patients in phase II of the study, the sensitivity of our cutoff was
      86% and the specificity was 96.7%. CONCLUSIONS: This study shows that an
      objective VA test using OKN responses can be effective in predicting real VA and
      detecting VA of >20/200.

PMID- 21862641
TI  - Retinal gene expression and visually evoked behavior in diabetic long evans rats.
AB  - PURPOSE: Patients with diabetic retinopathy may experience severe vision loss due
      to macular edema and neovascularization secondary to vascular abnormalities.
      However, before these abnormalities become apparent, there are functional
      deficits in contrast sensitivity, color perception, and dark adaptation. The
      goals of this study are to evaluate early changes (up to 3 months) in retinal
      gene expression, selected visual cycle proteins, and optokinetic tracking (OKT)
      in streptozotocin (STZ)-induced diabetic rats. METHODS: Retinal gene expression
      in diabetic Long Evans rats was measured by whole genome microarray 7 days, 4
      weeks, and 3 months after the onset of hyperglycemia. Select gene and protein
      changes were probed by polymerase chain reaction (PCR) and immunohistochemistry,
      respectively, and OKT thresholds were measured using a virtual optokinetics
      system. RESULTS: Microarray analysis showed that the most consistently affected
      molecular and cellular functions were cell-to-cell signaling and interaction,
      cell death, cellular growth and proliferation, molecular transport, and cellular
      movement. Further analysis revealed reduced expression of several genes encoding
      visual cycle proteins including lecithin/retinol acyltransferase (LRAT), retinal
      pigment epithelium (RPE)-specific protein 65 kDa (RPE65), and RPE retinal G
      protein-coupled receptor (RGR). These molecular changes occurred simultaneously
      with a decrease in OKT thresholds by 4 weeks of diabetes. Immunohistochemistry
      revealed a decrease in RPE65 in the RPE layer of diabetic rats after 3 months of
      hyperglycemia. CONCLUSIONS: The data presented here are further evidence that
      inner retinal cells are affected by hyperglycemia simultaneously with blood
      retinal barrier breakdown, suggesting that glial and neuronal dysfunction may
      underlie some of the early visual deficits in persons with diabetes.

PMID- 21862642
TI  - Differential association of serum lipids with diabetic retinopathy and diabetic
      macular edema.
AB  - PURPOSE: To assess the association of serum lipids with diabetic retinopathy
      (DR), diabetic macular edema (DME), and macular thickness in adults with
      diabetes. METHODS: Diabetic patients aged >= 18 years were prospectively
      recruited from specialized eye clinics in Melbourne, Australia. Fasting total-C
      (cholesterol), triglyceride, HDL-C, non-HDL-C, and LDL-C were assessed. DR was
      graded from fundus photographs and classified into mild, moderate, severe
      nonproliferative, and proliferative DR and separately graded for the presence of
      DME, including clinically significant macular edema (CSME). Macular thickness was
      assessed using optical coherence tomography (OCT). RESULTS: A total of 500
      participants (median age, 65 years) were examined. DR, DME, and CSME were present
      in 321 (66.2%), 149 (33.0%), and 68 (15.0%) patients, respectively. Serum lipid
      levels were not related to DR or DME. In multivariate models adjusted for
      traditional risk factors and lipid medications, persons with higher total-, LDL-,
      and non-HDL-C were more likely to have CSME (odds ratio of 1.54, 1.49, and 1.63
      per 1-SD increase, respectively; all P < 0.05). No association was found for
      serum lipids with macular thickness, as assessed by OCT. The pattern of these
      associations remained similar in both type 1 and type 2 diabetes, although it was
      statistically significant only in type 2 diabetes. CONCLUSIONS: Serum lipids are
      independently associated with the CSME, but not with DR, mild or moderate DME, or
      macular thickness. These data reflect the different impact of hyperlipidemia in
      the pathogenesis of DR and DME and may explain the discrepancies in previous
      studies.

PMID- 21862643
TI  - The TAg-RB murine retinoblastoma cell of origin has immunohistochemical features
      of differentiated Muller glia with progenitor properties.
AB  - PURPOSE: Human retinoblastoma arises from an undefined developing retinal cell
      after inactivation of RB1. This is emulated in a murine retinoblastoma model by
      inactivation of pRB by retinal-specific expression of simian virus 40 large T
      antigen (TAg-RB). Some mutational events after RB1 loss in humans are
      recapitulated at the expression level in TAg-RB, supporting preclinical evidence
      that this model is useful for comparative studies between mouse and human. Here,
      the characteristics of the TAg-RB cell of origin are defined. METHODS: TAg-RB
      mice were killed at ages from embryonic day (E)18 to postnatal day (P)35. Tumors
      were analyzed by immunostaining, DNA copy number PCR, or real-time quantitative
      RT-PCR for TAg protein, retinal cell type markers, and retinoblastoma-relevant
      genes. RESULTS: TAg expression began at P8 in a row of inner nuclear layer cells
      that increased in number through P21 to P28, when clusters reminiscent of small
      tumors emerged from cells that escaped a wave of apoptosis. Early TAg-expressing
      cells coexpressed the developmental marker Chx10 and glial markers CRALBP,
      clusterin, and carbonic anhydrase II (Car2), but not TuJ1, an early neuronal
      marker. Emerging tumors retained expression of only Chx10 and carbonic anhydrase
      II. As with human retinoblastoma, TAg-RB tumors showed decreased Cdh11 DNA copy
      number and gain of Kif14 and Mycn. It was confirmed that TAg-RB tumors lose
      expression of tumor suppressor cadherin-11 and overexpress oncogenes Kif14, Dek,
      and E2f3. CONCLUSIONS: TAg-RB tumors displayed molecular similarity to human
      retinoblastoma and origin in a cell with features of differentiated Muller glia
      with progenitor properties.

PMID- 21862645
TI  - En face optical coherence tomography of inner retinal defects after internal
      limiting membrane peeling for idiopathic macular hole.
AB  - PURPOSE: To describe the appearance of inner retinal defects using en face
      spectral domain optical coherence tomography (SD-OCT) after idiopathic full
      thickness macular hole (FTMH) surgery, referred to as concentric macular dark
      spots (CMDS). METHODS: In a retrospective cohort study, the authors evaluated 36
      eyes of 36 patients with large idiopathic MH (>400 MUm) who underwent standard
      three-port pars plana vitrectomy with internal limiting membrane (ILM) peeling.
      All patients were analyzed using B-scan and C-scan en face SD-OCT before and
      after surgery to determinate the OCT pattern of the retinal surface. RESULTS:
      Mean follow-up was 10 months (+/-8.45 SD; range, 3-30 months). Three months after
      surgery 36 of 36 eyes (100%) showed a CMDS appearance on en face SD-OCT images.
      Anatomic success rate was 100% (36/36 eyes) after a single surgical procedure.
      Once they were evident, these dark spots observed on the retinal surface were not
      progressive and remained stable over time. CONCLUSIONS: Inner retinal defects
      frequently occurred after idiopathic MH surgery when ILM was peeled. To the
      authors' knowledge, this feature has not been previously reported using an en
      face SD-OCT imaging, and it consisted of numerous CMDS in the same direction of
      the optic nerve fibers. All patients in the study showed this typical OCT pattern
      3 months after surgery. Thus, the authors suggest that this is a helpful,
      noninvasive technique to assess complete ILM removal in FTMH surgery if CMDS
      appearance on the retinal surface is reported.

PMID- 21862644
TI  - Differential expression of claudins in retinas during normal development and the
      angiogenesis of oxygen-induced retinopathy.
AB  - PURPOSE: Angiogenesis accompanies several retinal pathologies that impair the
      inner blood-retinal barrier. Claudins are key structural and functional proteins
      of the barrier. This study compared the expression of claudins during the normal
      angiogenesis of development with that of oxygen-induced retinopathy. METHODS:
      Real-time PCR was used to monitor mRNA from postnatal day 8 (P8) to P21 in normal
      mice and oxygen-induced retinopathy (OIR) mice. Protein expression was monitored
      by immunoblotting and immunofluorescence. Isolectin B4 was used to identify blood
      vessels and occludin was used to identify tight junctions. Neovascularization and
      permeability were monitored using FITC-dextran and Evans blue. RESULTS: The mRNA
      of claudin-1, -2, -3, -4, -5, -12, -22, and -23 was developmentally regulated,
      but only claudin-1, -2, and -5 were found in the tight junctions of retinal
      vessels. OIR induced the formation of leaky neovascular vessels. The mRNA and
      protein of claudin-2 and -5 were overexpressed, whereas claudin-1 and occludin
      were unaffected. Despite their overexpression, each claudin was distributed
      throughout the cell, especially in the neovascular tufts. Occludin was retained
      at the lateral membranes but exhibited a punctate distribution. CONCLUSIONS:
      Claudin-1, -2, and -5 are the most prominent claudins of the inner blood-retinal
      barrier. The pathologic angiogenesis induced by oxygen formed a leaky barrier due
      to the mislocalization of these claudins. Studies of the mechanisms that regulate
      the intracellular distribution of claudins may lead to new therapeutic approaches
      for retinal vascular disease.

PMID- 21862646
TI  - Simple estimation of clinically relevant lesion volumes using spectral domain
      optical coherence tomography in neovascular age-related macular degeneration.
AB  - PURPOSE: To evaluate simple methods of estimating the volume of clinically
      relevant features in neovascular age-related macular degeneration (NVAMD) using
      spectral domain-optical coherence tomography (SD-OCT). METHODS: Using a database
      of NVAMD cases imaged with macular cube (512 A-scans * 128 B-scans) SD-OCT scans,
      the authors retrospectively selected visits where cystoid macular edema (CME),
      subretinal fluid (SRF), or pigment epithelial detachments (PEDs) were evident.
      Patients with single visits were analyzed in the cross-sectional analysis (CSA)
      and those with a baseline visit and three or more follow-up visits in the
      longitudinal analysis (LA). The volume of each feature was measured by manual
      grading using validated grading software. Simplified measurements for each
      feature included: number of B-scans or A-scans involved and maximum height.
      Automated measurements of total macular volume and foveal central subfield were
      also collected from each machine. Correlations were performed between the volumes
      measured with 3D-OCTOR, automated measurements, and the simplified measures.
      RESULTS: Forty-five visits for 25 patients were included in this study: 26 cube
      scans from 26 eyes of 25 patients in the CSA and 24 scans from 5 eyes of 5
      patients in the LA. The simplified measures that correlated best with manual
      grading in the CSA group were maximum lesion height for CME (r2 value = 0.96) and
      B-scan count for SRF and PED volume (r2 values of 0.88 and 0.70). In the LA
      group, intervisit differences were correlated. Change in B-scan count correlated
      well with change in SRF volume (r2 = 0.97), whereas change in maximum height
      correlated with change in CME and PED volume (r2 = 0.98 and 0.43, respectively).
      CONCLUSIONS: These data suggest that simplified estimators of some NVAMD lesion
      volumes exist and are accessible by clinicians without the need for specialized
      software or time-consuming manual segmentation. These simple approaches could
      enhance quantitative disease monitoring strategies in clinical trials and
      clinical practice.

PMID- 21862647
TI  - Racial differences in the prevalence of diabetes but not diabetic retinopathy in
      a multi-ethnic Asian population.
AB  - PURPOSE: To compare the prevalence and risk factors of diabetes (DM) and diabetic
      retinopathy (DR) in a multi-ethnic Asian population of Chinese, Malays, and
      Indians in Singapore. METHODS: A total of 2919 individuals participated in a
      population-based, cross-sectional study in Singapore of Chinese (n = 1633),
      Malays (n = 658), and Indians (n = 628) aged 40 to 95 years, with retinal
      photographs, graded using the Early Treatment Diabetic Retinopathy Study (ETDRS)
      severity scale. DM was defined as fasting plasma glucose >= 7 mmol/L, self
      reported physician-diagnosed diabetes, and use of glucose-lowering medication.
      RESULTS: The overall age-standardized prevalence of diabetes was 13.8% (Chinese,
      11.5%; Malays, 17.1%; and Indians, 21.6%; P < 0.0001). Among persons with
      diabetes (n = 401), the overall age-standardized prevalence of DR was 25.4%
      (20.1%, 24.8%, and 28.9% in Chinese, Malays, and Indians, respectively; P =
      0.290). In multivariate analysis, longer diabetes duration (odds ratio [OR],
      1.05; 95% confidence interval [CI], 1.01-1.09, per year increase), higher
      glycated hemoglobin (OR 1.25; 95% CI, 1.01-1.54, per 1% increase), and serum
      creatinine levels (OR, 1.01; 95% CI, 1.00-1.03, per mg/dL increase) were the
      independent risk factors of DR in the whole population. Race was not found to be
      associated with DR (OR, 1.35; CI, 1.00-1.83). The associations of major risk
      factors with DR were similar among the three ethnic groups. CONCLUSIONS: There
      was a significant difference in the prevalence of diabetes between Chinese,
      Malays, and Indians. The main risk factors of DR, similar among the three ethnic
      groups, are longer diabetes duration, higher hbA1c, and higher creatinine levels.
      No significant racial differences were found in the prevalence of DR among
      persons with diabetes.

PMID- 21862649
TI  - Fluvastatin downregulates VEGF-A expression in TNF-alpha-induced retinal vessel
      tortuosity.
AB  - PURPOSE: To investigate the effect of tumor necrosis factor alpha (TNF-alpha) on
      the mouse retinal vasculature, function, and expression of vascular endothelial
      growth factor-A (VEGF-A) in the retina and retinal pigment epithelium (RPE) and
      to evaluate the protective effect of statin therapy (fluvastatin) on retinal
      vascular and functional changes. METHODS: A single intravenous injection of
      murine TNF-alpha (8 MUg/kg body weight) was administered to one group of mice
      (TNF group). In the second group of mice (TNF+Statin group), a single dose of TNF
      alpha was followed by 28 days oral medication of fluvastatin (10 mg/kg/d), and an
      equivalent volume of saline was administered to the third group (Control group).
      After 28 days, electroretinography (ERG) and fundus photography were performed.
      Eyes were collected for cell and molecular studies. Transcript levels of VEGF-A
      in retina and RPE were quantified using real-time polymerase chain reaction, and
      protein expression was analyzed by Western blot and immunostaining. RESULTS: TNF
      alpha-injected mice showed retinal vessel tortuosity, structural change, and
      altered retinal function. Fluvastatin-treated mice exhibited retinal vascular,
      structural, and functional changes almost similar to those of the control group.
      VEGF-A expression was significantly upregulated in the retina and RPE of TNF
      alpha-injected mice, and this was significantly downregulated in fluvastatin
      treated mice. CONCLUSIONS: This study shows that the TNF-alpha-induced
      inflammatory process results in the alteration of retinal microvasculature and
      function, and fluvastatin could be a potential therapy for treating/preventing
      retinal microvascular or inflammatory complications.

PMID- 21862648
TI  - Late-onset inner retinal dysfunction in mice lacking sigma receptor 1 (sigmaR1).
AB  - PURPOSE: Sigma receptor 1 (sigmaR1) is expressed abundantly in the eye, and
      several reports suggest that this putative molecular chaperone plays a role in
      lens cell survival, control of intraocular pressure (IOP), and retinal
      neuroprotection. The present study examined the consequence of the absence of
      sigmaR1 on ocular development, structure, and function. METHODS: Wild-type
      (sigmaR1+/+), heterozygous (sigmaR1+/-), and homozygous (sigmaR1-/-, knockout)
      mice aged 5 to 59 weeks were subjected to comprehensive electrophysiological
      testing and IOP measurement. The eyes were examined by light and electron
      microscopy and subjected to morphometric examination and detection of apoptosis.
      RESULTS: Cornea and lens of sigmaR1-/- mice were similar to wild-type mice in
      morphologic appearance at all ages examined, and IOP was within normal limits.
      Comprehensive ERG and morphometric analyses initially yielded normal findings in
      the sigmaR1-/- mice compared with those in the wild-type. By 12 months, however,
      significantly decreased ERG b-wave amplitudes and diminished negative scotopic
      threshold responses, consistent with inner retinal dysfunction, were detected in
      sigmaR1-/- mice. Concomitant with these late-onset changes were increased TUNEL-
      and active caspase 3-positive cells in the inner retina and significant loss of
      cells in the ganglion cell layer, particularly in the central retina. Before
      these functional and structural abnormalities, there was ultrastructural evidence
      of axonal disruption in the optic nerve head of sigmaR1-/- mice as early as 6
      months of age, although there were no alterations observed in retinal
      vascularization in sigmaR1-/- mice. CONCLUSIONS: These data suggest that lack of
      sigmaR1 leads to development of late-onset retinal dysfunction with similarities
      to optic neuropathy.

PMID- 21862650
TI  - Mpdz null allele in an avian model of retinal degeneration and mutations in human
      leber congenital amaurosis and retinitis pigmentosa.
AB  - PURPOSE: To identify the defective gene in the sex-linked, recessively inherited
      retinal dysplasia and degeneration (rdd) chicken and to search for the human
      equivalent disease. METHODS: Microsatellites from chicken chromosome Z were
      genotyped in 77 progeny of a carrier male (rdd/+) and an affected female (rdd/W),
      and candidate genes were sequenced. Retinal cross-sections from rdd and wild-type
      birds were analyzed by immunohistology. The human orthologous gene was screened
      in a panel of archival DNAs from 276 patients with retinitis pigmentosa (RP) or
      Leber congenital amaurosis (LCA) using melting curve analysis and DNA sequencing.
      RESULTS: The rdd locus was refined to an approximately 3-Mb region on chromosome
      Z. Sequence analysis identified a C->T change in the mpdz gene that created a
      premature stop codon (c.1372C->T, p.R458X), which segregated with the disease
      phenotype. As expected, the full-length mpdz protein was absent in rdd retinas,
      but in wild-type birds, it localized to the retinal outer limiting membrane,
      where it may have a role in the interactions between photoreceptors and Muller
      glia cells. The screen to identify the human equivalent disease found 10
      heterozygous variants in the orthologous gene in patients with RP (three missense
      and two null alleles) and LCA (four missense and one null allele). CONCLUSIONS:
      These findings reveal that MPDZ is essential for normal development of the retina
      and may have a role in maintaining photoreceptor integrity. The identification of
      human mutations suggests that MPDZ plays a role in human retinal disease, but the
      precise nature of this role remains to be determined.

PMID- 21862651
TI  - Automated analysis of optic nerve images for detection and staging of
      papilledema.
AB  - PURPOSE: To develop an automated system that analyzes digital fundus images for
      staging and monitoring of optic disc edema (i.e., papilledema), due to raised
      intracranial pressure. METHODS: A total of 294 retrospective, digital photographs
      of the right and left eyes of 39 subjects with papilledema acquired over the span
      of 2 years were used. Software tools were developed to analyze three features of
      papilledema from digital fundus photographs: (1) sharpness of the optic disc
      border, (2) discontinuity along major vessels overlying the optic nerve, and (3)
      texture properties of the peripapillary retinal nerve fiber layer (RNFL). A
      classifier used these features to assign a grade of papilledema according to a
      standard protocol used by an expert neuro-ophthalmologist (RK). RESULTS: The
      algorithm showed substantial agreement (kappa = 0.71, P < 0.001) with the neuro
      ophthalmologist when grading papilledema per patient. Vessel features showed
      statistical significance (P < 0.05) in differentiating grades 0, 1, and 2 from
      grades 3 and 4, whereas disc obscuration differentiated grades 0 or 1 from the
      rest (P < 0.05). CONCLUSIONS: These results show that this algorithm can be used
      to automatically grade papilledema. The algorithm provides objective and
      quantitative assessment of the stage of papilledema with accuracy that is
      comparable to grading by a neuro-ophthalmologist. One application is in rapid
      assessment of digital optic nerve photographs acquired in clinical, intensive
      care, and emergency response settings by nonophthalmologists to evaluate for the
      presence and severity of papilledema, due to intracranial hypertension.

PMID- 21862652
TI  - Age-related eye disease and mobility limitations in older adults.
AB  - PURPOSE: To examine the extent of mobility limitations in patients with age
      related macular degeneration (AMD), glaucoma, or Fuchs' corneal dystrophy
      compared with that in a control group of older adults with good vision. METHODS:
      Two hundred seventy-two patients (68 with AMD, 49 with Fuchs' dystrophy, 82 with
      glaucoma, and 73 controls) from the ophthalmology clinics of Maisonneuve-Rosemont
      Hospital (Montreal, Canada) participated in a cross-sectional study from
      September 2009 until February 2011. Control patients who had normal visual acuity
      and visual fields were recruited from the same clinics. Questionnaire (life
      space, falls, and driving) and performance-based (one-legged balance test, Timed
      Up and Go [TUG] test) mobility data were collected; visual acuity, contrast
      sensitivity, and visual field were measured; and the medical record was reviewed.
      RESULTS: The three eye diseases were associated with different patterns of
      mobility limitations. Patients with glaucoma had the most types of mobility
      limitations, as they had reduced life-space scores, had worse TUG scores, were
      less likely to drive, and were more likely to have poor balance than the control
      group (P < 0.05). Compared with the controls, patients with AMD and Fuchs'
      corneal dystrophy had reduced life-space scores and were less likely to drive (P
      < 0.05). CONCLUSIONS: The results suggest that eye diseases, especially glaucoma,
      restrain the mobility of older people in many different ways. It is important to
      further explore the impact of eye disease on mobility in this population, to
      develop interventions that could help affected older adults maintain their
      independence.

PMID- 21862653
TI  - Atypical retardation patterns in scanning laser polarimetry are associated with
      low peripapillary choroidal thickness.
AB  - PURPOSE: Scanning laser polarimetry (SLP) results can be affected by an atypical
      retardation pattern (ARP). One reason for an ARP is the birefringence of the
      sclera. The purpose of this study was to investigate the influence of the
      peripapillary choroidal thickness (pChTh) on the occurrence of ARP. METHODS: One
      hundred ten healthy subjects were investigated with SLP and spectral domain OCT.
      pChTh was measured in B-scan images at 768 positions using semiautomatic
      software. Values were averaged to 32 sectors and the total peripapillary mean.
      Subjects were divided into four groups according to the typical scan score (TSS)
      provided by the GDxVCC: group 1 TSS, 100; group 2 TSS, 90-99; group 3 TSS, 80-89;
      group 4 TSS, <80. RESULTS: Mean pChTh (+/- SD) in 110 healthy subjects was 141
      MUm (+/-49 MUm). There was a significant correlation between pChTh and TSS (r =
      0.608; P < 0.001). In TSS groups 1 to 4, mean pChTh was 168 MUm (+/-38 MUm), 148
      MUm (+/- 48 MUm), 119 MUm (+/-35 MUm), and 92 (+/-42 MUm). Mean pChTh of TSS
      groups 3 and 4 was significantly lower than that of TSS group 1 (P < 0.001).
      CONCLUSIONS: Low values of TSS resulting from the appearance of ARP in SLP are
      associated with low peripapillary choroidal thickness. Reduced choroidal
      thickness may result in an increased amount of confounding light getting to the
      SLP light detectors.

PMID- 21862654
TI  - Effect of infliximab on gene expression profiling in Behcet's disease.
AB  - PURPOSE: Recent studies have demonstrated that a new anti-tumor necrosis factor
      (TNF)-alpha antibody, infliximab, is effective in controlling ocular inflammatory
      attacks in Behcet's disease. In this study, the effect of infliximab on gene
      expression patterns in peripheral blood mononuclear cells of Behcet's disease
      patients was investigated before and after initiation of infliximab treatment.
      METHODS: A human whole-genome microarray of 54,359 genes was used to analyze mRNA
      expression profiles of peripheral blood mononuclear cells obtained from four
      patients (three women, one man, 21-64 years at age) at baseline and at 22 weeks
      after initiation of infliximab. Quantitative polymerase chain reaction (PCR)
      analysis was performed for selected up- or downregulated genes, to confirm the
      microarray results. RESULTS: Anti-TNF-alpha therapy reduced the frequency of
      ocular episodes in three of four patients. Among inflammatory cytokine-related
      genes, TNF blockade reduced expression of interleukin (IL)-1 receptor type 2,
      interferon-gamma receptors, IL6, IL6 receptor, gp130, and IL17 receptors.
      Furthermore, gene expression of Toll-like receptor 2 (TLR2), receptor for
      mycobacterial glycolipid (C-type lectin domain family 4, member E: CLEC4E), and
      complexin 2 (CPLX2) was downregulated in all patients. CONCLUSIONS: Several up-
      or downregulated genes identified in this study may be candidates for further
      investigation in identifying the molecular mechanism of infliximab in the
      treatment of Behcet's disease with refractory uveoretinitis.

PMID- 21862655
TI  - Reading strategies in infantile nystagmus syndrome.
AB  - PURPOSE: The adaptive strategies adopted by individuals with infantile nystagmus
      syndrome (INS) during reading are not clearly understood. Eye movement recordings
      were used to identify ocular motor strategies used by patients with INS during
      reading. METHODS: Eye movements were recorded at 500 Hz in 25 volunteers with INS
      and 7 controls when reading paragraphs of text centered at horizontal gaze angles
      of -20 degrees , -10 degrees , 0 degrees , 10 degrees , and 20 degrees . At each
      location, reading speeds were measured, along with logMAR visual acuity and
      nystagmus during gaze-holding. Adaptive strategies were identified from slow and
      quick-phase patterns in the nystagmus waveform. RESULTS: Median reading speeds
      were 204.3 words per minute in individuals with INS and 273.6 words per minute in
      controls. Adaptive strategies included (1) suppression of corrective quick phases
      allowing involuntary slow phases to achieve the desired goal, (2) voluntarily
      changing the character of the involuntary slow phases using quick phases, and (3)
      correction of involuntary slow phases using quick phases. Several individuals
      with INS read more rapidly than healthy control volunteers. CONCLUSIONS: These
      findings demonstrate that volunteers with INS learn to manipulate their nystagmus
      using a range of strategies to acquire visual information from the text. These
      strategies include taking advantage of the stereotypical and periodic nature of
      involuntary eye movements to allow the involuntary eye movements to achieve the
      desired goal. The versatility of these adaptations yields reading speeds in those
      with nystagmus that are often much better than might be expected, given the
      degree of foveal and ocular motor deficits.

PMID- 21862656
TI  - The influence of alloxan-induced diabetes on Muller cell contraction-promoting
      activities in vitreous.
AB  - PURPOSE: Previous studies from this laboratory revealed that vitreous insulin
      like growth factor biological activity increases in diabetes and that this change
      can precede the onset of proliferative diabetic retinopathy. The goal of this
      study was to characterize this phenomenon in an animal model of alloxan-induced
      diabetes. METHODS: Swine made diabetic with intravenous alloxan were euthanized
      at times varying from 0 to 90 days. Vitreous samples from normal and diabetic
      swine were evaluated for changes in Muller cell contraction-promoting activity,
      the presence of insulin-like growth factor binding protein (IGFBP), and carbonic
      anhydrase-I and -II. Ocular tissues from these animals were also evaluated for
      changes in contraction-promoting growth factors and IGFBP message levels.
      RESULTS: Alloxan-induced diabetes is associated with significant increases in
      vitreous Muller cell contraction-promoting activity that are present in as few as
      30 days and are sustained for at least 90 days. Biochemical studies revealed that
      the increases cannot be attributed to loss of growth factor-attenuating IGFBPs,
      changes in local expression of contraction-promoting growth factors, or vitreous
      hemorrhage. CONCLUSIONS: The previously reported increases in Muller cell
      contraction-promoting activity detected in human diabetic vitreous are present in
      diabetic swine within 30 days of chemical induction. The increase does not appear
      to be attributable to loss of growth factor control, increases in local growth
      factor expression, or vitreous hemorrhage, suggesting that other mechanisms are
      involved. It is the authors' speculation that diabetes induces blood-vitreous
      barrier changes that allow a different subset of plasma proteins to enter
      vitreous fluids.

PMID- 21862657
TI  - Fully equipped to defeat the pulmonary vein potentials: on the quest for sinus
      rhythm.

PMID- 21862658
TI  - The real cost of treating atrial fibrillation.

PMID- 21862659
TI  - Isoform-selective activation of human constitutive androstane receptor by Ginkgo
      biloba extract: functional analysis of the SV23, SV24, and SV25 splice variants.
AB  - Naturally occurring splice variants of human constitutive androstane receptor
      (hCAR) exist, including hCAR-SV23 (insertion of amino acids SPTV), hCAR-SV24
      (APYLT), and hCAR-SV25 (SPTV and APYLT). An extract of Ginkgo biloba was reported
      to activate hCAR-SV24 and the wild type (hCAR-WT). However, it is not known
      whether it selectively affects hCAR splice variants, how it activates hCAR
      isoforms, and which chemical is responsible for the effects of the extract.
      Therefore, we evaluated the impact of G. biloba extract on the functionality of
      hCAR-SV23, hCAR-SV24, hCAR-SV25, and hCAR-WT and compared it with that of
      phenobarbital, di-(2-ethylhexyl)phthalate (DEHP), 6-(4-chlorophenyl)imidazo[2,1
      b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), and 1,4-bis
      [2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in cell-based reporter gene assays.
      Among the hCAR splice variants investigated, only hCAR-SV23 was activated by G.
      biloba extract, and this required cotransfection of a retinoid X receptor alpha
      (RXRalpha) expression plasmid. The extract activated hCAR-SV23 to a lesser extent
      than hCAR-WT, but ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and
      bilobalide were not responsible for the effects of the extract. CITCO activated
      hCAR-SV23, hCAR-SV24, and hCAR-WT. By comparison, phenobarbital activated hCAR
      WT, whereas DEHP activated hCAR-SV23, hCAR-SV24 (with exogenous RXRalpha
      supplementation), and hCAR-WT. TCPOBOP did not affect the activity of any of the
      isoforms. G. biloba extract and phenobarbital did not bind or recruit
      coactivators to the ligand-binding domains of hCAR-WT and hCAR-SV23, whereas
      positive results were obtained with the controls (CITCO for hCAR-WT and DEHP for
      hCAR-SV23). In conclusion, G. biloba extract activates hCAR in an isoform
      selective manner, and hCAR-SV23, hCAR-SV24, and hCAR-WT have overlapping, but
      distinct, sets of ligands.

PMID- 21862660
TI  - Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates
      hepatic stellate cell apoptosis by blocking the inhibitor of kappaB kinase
      alpha/inhibitor of kappaB-alpha/nuclear factor-kappaB pathway.
AB  - Hepatic stellate cells (HSC) play a pivotal role in liver fibrosis, and the
      clearance of activated HSC by apoptosis is associated with the resolution of
      liver fibrosis. The development of strategies that promote this process in a
      selective way is therefore important. We evaluated the effects of indole-3
      carbinol (I3C), a nutritional component derived from vegetables from the Brassica
      family, on liver fibrosis and HSC apoptosis. The in vivo therapeutic effects of
      I3C were monitored in three rat models of liver fibrosis induced by porcine
      serum, bile duct ligation, or multiple hepatotoxic factors, and its proapoptotic
      effect and molecular mechanism were studied in vitro in HSC-T6, a rat HSC line.
      The results showed that I3C treatment significantly reduced the number of
      activated HSC in the livers of rats with liver fibrosis. In histopathology, I3C
      reduced hepatocyte degeneration and necrosis, accelerated collagen degradation,
      and promoted the reversal of liver fibrosis. I3C prescribed to HSC-T6 resulted in
      morphologic alterations typical of apoptosis and DNA cleavage to a nucleosomal
      ladder. Moreover, I3C significantly increased the HSC-T6 apoptosis rate and the
      expression ratio of Bax to Bcl-2. High-throughput protein array analysis
      indicated that the tumor necrosis factor-alpha/nuclear factor-kappaB (NF-kappaB)
      signal pathway participated in I3C-induced HSC-T6 apoptosis. Western blot and
      electrophoretic mobility-shift assay confirmed that I3C inhibited the
      phosphorylation of inhibitor of kappaB kinase alpha and inhibitor of kappaB-alpha
      and NF-kappaB DNA binding activity. In conclusion, I3C could promote the reverse
      process of liver fibrosis in vivo and induce apoptosis of activated HSC in vitro,
      which indicates the use of I3C as a potential therapeutic agent in liver fibrosis
      treatment.

PMID- 21862662
TI  - Abstracts from the 31st Annual Meeting of the National Academy of
      Neuropsychology, Marco Island, Florida, November 16-19, 2011.

PMID- 21862661
TI  - Broadening horizons of antibody engineering.

PMID- 21862666
TI  - Patients with surgically cured primary hyperparathyroidism have a reduced quality
      of life compared with population-based healthy sex-, age-, and season-matched
      controls.
AB  - OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with feelings of
      fatigue and depression, as well as limitation to physical and mental functioning.
      These quality of life (QoL) characteristics improve after parathyroidectomy.
      However, whether former patients fully regain QoL compared with healthy controls
      is largely unknown. DESIGN AND PATIENTS: Cross-sectional study. Fifty-one former
      PHPT patients, successfully treated by surgery (mean time since parathyroidectomy
      7.4 (range 5-15) years), and 51 sex- and age-matched healthy controls. METHODS:
      The 36-item Short-Form Health Survey version 2 and the WHO-Five Well-being Index.
      The surveys included questions on overall physical and mental health,
      functioning, and limitation in daily life activities. RESULTS: Former patients
      scored significantly lower compared with controls in physical functioning
      (P=0.01), role limitation caused by emotional problems (P=0.01), vitality
      (P<0.001), and general health (P=0.01). Compared with the controls, cases had a
      lower median (interquartile range) score of physical component summary (PCS; 54.9
      (47.9-58.7) vs 49.6 (45.2-55.9), P=0.03) and mental component summary (MCS; 55.4
      (49.7-58.1) vs 52.5 (44.7-55.5), P=0.04). There was no association between time
      since operation and PCS or MCS. Compared with controls, cases had higher body
      mass index (BMI; 26.0+/-4.7 vs 28.8+/-6.0 kg/m(2), P<0.001) and a higher
      frequency of cardiovascular diseases (CVD; 41.2 vs 62.7%, P=0.03). After
      adjustment for differences in BMI and CVD, PCS did no longer differ between
      groups. However, adjustments did not change the finding of a lower MCS in cases
      compared with controls. CONCLUSION: Even though QoL may improve substantially
      after surgery, former PHPT patients still have reduced QoL compared with healthy
      controls.

PMID- 21862667
TI  - Antibodies to HIV integrase catalyze site-specific degradation of their antigen.
AB  - HIV-1 integrase (IN) catalyzes integration of a DNA copy of the viral genome into
      the host genome. In contrast to canonical proteases (trypsin, chymotrypsin and
      proteinase K), IgGs and IgMs isolated from HIV-infected patients by affinity
      chromatography on immobilized IN specifically hydrolyzed only IN but not many
      other tested intact globular proteins. The sites of IN cleavage determined by
      MALDI mass spectrometry were localized mainly within seven known immunodominant
      regions of IN. Thin layer chromatography analysis has shown that the abzymes
      (Abzs) could also cleave 17 to 22-mer oligopeptides (OPs) corresponding to the
      immunodominant regions of IN sequence with a much higher rate than non-specific
      long peptides or three- and tetrapeptides of various sequence. Therefore, a
      prolonged incubation of IN with AIDS IgGs and IgMs having high catalytic activity
      usually produces many OPs of different length. Since anti-IN IgGs and IgMs can
      efficiently hydrolyze IN, a positive role of the Abzs in counteracting the
      infection is possible.

PMID- 21862668
TI  - HCF243 encodes a chloroplast-localized protein involved in the D1 protein
      stability of the arabidopsis photosystem II complex.
AB  - Numerous auxiliary nuclear factors have been identified to be involved in the
      dynamics of the photosystem II (PSII) complex. In this study, we characterized
      the high chlorophyll fluorescence243 (hcf243) mutant of Arabidopsis (Arabidopsis
      thaliana), which shows higher chlorophyll fluorescence and is severely deficient
      in the accumulation of PSII supercomplexes compared with the wild type. The
      amount of core subunits was greatly decreased, while the outer antenna subunits
      and other subunits were hardly affected in hcf243. In vivo protein-labeling
      experiments indicated that the synthesis rate of both D1 and D2 proteins
      decreased severely in hcf243, whereas no change was found in the rate of other
      plastid-encoded proteins. Furthermore, the degradation rate of the PSII core
      subunit D1 protein is higher in hcf243 than in the wild type, and the assembly of
      PSII is retarded significantly in the hcf243 mutant. HCF243, a nuclear gene,
      encodes a chloroplast protein that interacts with the D1 protein. HCF243 homologs
      were identified in angiosperms with one or two copies but were not found in lower
      plants and prokaryotes. These results suggest that HCF243, which arose after the
      origin of the higher plants, may act as a cofactor to maintain the stability of
      D1 protein and to promote the subsequent assembly of the PSII complex.

PMID- 21862669
TI  - Mutations in MYB3R1 and MYB3R4 cause pleiotropic developmental defects and
      preferential down-regulation of multiple G2/M-specific genes in Arabidopsis.
AB  - R1R2R3-Myb proteins represent an evolutionarily conserved class of Myb family
      proteins important for cell cycle regulation and differentiation in eukaryotic
      cells. In plants, this class of Myb proteins are believed to regulate the
      transcription of G2/M phase-specific genes by binding to common cis-elements,
      called mitosis-specific activator (MSA) elements. In Arabidopsis (Arabidopsis
      thaliana), MYB3R1 and MYB3R4 act as transcriptional activators and positively
      regulate cytokinesis by activating the transcription of KNOLLE, which encodes a
      cytokinesis-specific syntaxin. Here, we show that the double mutation myb3r1
      myb3r4 causes pleiotropic developmental defects, some of which are due to
      deficiency of KNOLLE whereas other are not, suggesting that multiple target genes
      are involved. Consistently, microarray analysis of the double mutant revealed
      altered expression of many genes, among which G2/M-specific genes showed
      significant overrepresentation of the MSA motif and a strong tendency to be down
      regulated by the double mutation. Our results demonstrate, on a genome-wide
      level, the importance of the MYB3R-MSA pathway for regulating G2/M-specific
      transcription. In addition, MYB3R1 and MYB3R4 may have diverse roles during plant
      development by regulating G2/M-specific genes with various functions as well as
      genes possibly unrelated to the cell cycle.

PMID- 21862670
TI  - DEspR T/CATAAAA-box promoter variant decreases DEspR transcription and is
      associated with increased BP in Sardinian males.
AB  - Essential hypertension is highly prevalent in the elderly population, exceeding
      70% in people older than 60 yr of age, and remains a leading risk factor for
      heart disease, stroke, and chronic renal disease. Elucidation of genetic
      determinants is critical but remains a challenge due to its complex,
      multifactorial pathogenesis. We investigated the role DEspR promoter variants,
      previously associated with male essential hypertension susceptibility, in blood
      pressure (BP) regulation. We detected a single nucleotide polymorphism within the
      DEspR 5'-regulatory region associated with increased BP in a male Sardinian
      cohort accounting for 11.0 mmHg of systolic BP (P<10(-15)) and 9.3 mmHg of
      diastolic BP (P<10(-15)). Sequence analysis of three normotensive subjects
      homozygous for the rs6535847 "normotension-associated T-allele" identified a
      canonical TATAAAA-box in contrast to a CATAAAA-motif in three hypertensive
      subjects homozygous for the rs6535847 "hypertension-associated C-allele." In
      vitro analysis detected decreased transcription activity with the CATAAAA-motif
      promoter-construct compared with the canonical TATAAAA-box promoter-construct.
      Although BP did not differ between DEspR+/- knockout male mice and wild-type
      littermates at 6 mo of age, radiotelemetric BP measurements in 18 mo old inbred
      DEspR+/- knockout male mice known to have decreased DEspR RNA and protein
      detected higher systolic, mean, and diastolic BPs in DEspR+/- mice compared with
      littermate wild-type controls (P<0.05). Our results demonstrate that promoter
      variants in DEspR associated with hypertension susceptibility and increased BP in
      Sardinian males affect transcription levels, which then affect BP in an age
      dependent and male-specific manner. This finding is concordant with the late
      onset and sex-specific characteristics of essential hypertension, thus
      reiterating the mandate for sex-specific analyses and treatment approaches for
      essential hypertension.

PMID- 21862671
TI  - Knowledge, skills, and qualities for effectively facilitating an adolescent
      girls' group.
AB  - Nurses employed in a variety of school settings often rely on group-format
      approaches to support the health and well-being of adolescent girls. The process
      of selecting an effective facilitator, and evaluating the impact of a facilitator
      on intervention process and outcomes, is rarely described. The purpose of this
      article was to synthesize the literature regarding facilitator knowledge, skills,
      and qualities to provide school-based researchers and practitioners with a
      framework for selecting and evaluating group facilitators. Literature was
      reviewed between Fall of 2008 and Spring of 2011. Findings were synthesized into
      categories that provide the organization for this article (why groups, why a
      facilitator, and the knowledge, skills, and qualities of an effective girls'
      group facilitator). Nurses need to carefully identify, select, and equip those
      who serve as facilitators because group successes, evidenced in the ways girls
      grow and support each other in growth, are the result of a successful, well
      matched facilitator-group participant experience.

PMID- 21862672
TI  - Exome diagnostics: already a reality?

PMID- 21862673
TI  - A new ocular phenotype associated with an unexpected but known systemic disorder
      and mutation: novel use of genomic diagnostics and exome sequencing.

PMID- 21862674
TI  - Identification of ADAMTS18 as a gene mutated in Knobloch syndrome.
AB  - BACKGROUND: Knobloch syndrome (KS) is a developmental disorder characterised by
      occipital skull defect, high myopia, and vitreo-retinal degeneration. Although
      genetic heterogeneity has been suspected, COL18A1 is the only known KS disease
      gene to date. OBJECTIVE: To identify a novel genetic cause of KS in a cohort of
      Saudi KS patients enrolled in this study. METHODS: When COL18A1 mutation was
      excluded, autozygosity mapping was combined with exome sequencing. RESULTS: In
      one patient with first cousin parents, COL18A1 was excluded by both linkage and
      direct sequencing. By filtering variants generated on exome sequencing using runs
      of autozygosity in this simplex case, the study identified ADAMTS18 as the only
      gene carrying a homozygous protein altering mutation. It was also shown that
      Adamts18 is expressed in the lens and retina in the developing murine eye.
      CONCLUSION: The power of combining exome and autozygome analysis in the study of
      genetics of autosomal recessive disorders, even in simplex cases, has been
      demonstrated.

PMID- 21862676
TI  - Preliminary investigation of visual attention to human figures in photographs:
      potential considerations for the design of aided AAC visual scene displays.
AB  - PURPOSE: Many individuals with complex communication needs may benefit from
      visual aided augmentative and alternative communication systems. In visual scene
      displays (VSDs), language concepts are embedded into a photograph of a
      naturalistic event. Humans play a central role in communication development and
      might be important elements in VSDs. However, many VSDs omit human figures. In
      this study, the authors sought to describe the distribution of visual attention
      to humans in naturalistic scenes as compared with other elements. METHOD:
      Nineteen college students observed 8 photographs in which a human figure appeared
      near 1 or more items that might be expected to compete for visual attention (such
      as a Christmas tree or a table loaded with food). Eye-tracking technology allowed
      precise recording of participants' gaze. The fixation duration over a 7-s viewing
      period and latency to view elements in the photograph were measured. RESULTS:
      Participants fixated on the human figures more rapidly and for longer than
      expected based on the size of these figures, regardless of the other elements in
      the scene. CONCLUSIONS: Human figures attract attention in a photograph even when
      presented alongside other attractive distracters. Results suggest that humans may
      be a powerful means to attract visual attention to key elements in VSDs.

PMID- 21862675
TI  - Differential associations between sensory response patterns and language, social,
      and communication measures in children with autism or other developmental
      disabilities.
AB  - PURPOSE: To examine patterns of sensory responsiveness (i.e.,
      hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may
      account for variability in social-communicative symptoms of autism and
      variability in language, social, and communication skill development in children
      with autism or other developmental disabilities (DDs). METHOD: Children with
      autistic disorder (AD; n = 72, mean age = 52.3 months) and other DDs (n = 44,
      mean age = 48.1 months) participated in a protocol measuring sensory response
      patterns; social-communicative symptoms of autism; and language, social, and
      communication skills. RESULTS: Hyporesponsiveness was positively associated with
      social-communicative symptom severity, with no significant group difference in
      the association. Hyperresponsiveness was not significantly associated with social
      communicative symptom severity. A group difference emerged for sensory seeking
      and social-communicative symptom severity, with a positive association for the AD
      group only. For the 2 groups of children combined, hyporesponsiveness was
      negatively associated with language skills and social adaptive skills. Sensory
      seeking also was negatively associated with language skills. These associations
      did not differ between the 2 groups. CONCLUSIONS: Aberrant sensory processing may
      play an important role in the pathogenesis of autism and other DDs as well as in
      the rate of acquisition of language, social, and communication skills.

PMID- 21862677
TI  - Resilience and stuttering: factors that protect people from the adversity of
      chronic stuttering.
AB  - PURPOSE: Chronic disorder can impose a significant negative mental health burden.
      This research was conducted to explore factors that may protect people from the
      adversity of chronic stuttering. METHOD: The study employed a population group
      cohort design. Participants included 200 adults who have stuttered since
      childhood, and the sample was divided into those who were classified as resilient
      and nonresilient on the basis of their global psychopathology scores. Protective
      factor differences between the 2 groups were determined using multivariate
      analysis of variance and unique contributors to psychopathology were isolated
      using multiple regression. RESULTS: Factors that significantly distinguished
      between groups included superior levels of health status, social support,
      vitality and social functioning, fewer physical limitations, and a greater sense
      of self-efficacy. Three unique contributors to adaptive outcomes were found: self
      efficacy, social support, and healthy social functioning. CONCLUSIONS: A number
      of factors were isolated that potentially protect individuals with chronic
      stuttering from developing psychopathology. The findings provide a better
      understanding of how people cope with a chronic fluency disorder.

PMID- 21862678
TI  - The MOC reflex during active listening to speech.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that active
      listening to speech would increase medial olivocochlear (MOC) efferent activity
      for the right vs. the left ear. METHOD: Click-evoked otoacoustic emissions
      (CEOAEs) were evoked by 60-dB p.e. SPL clicks in 13 normally hearing adults in 4
      test conditions for each ear: (a) in quiet; (b) with 60-dB SPL contralateral
      broadband noise; (c) with words embedded (at -3-dB signal-to-noise ratio [SNR])
      in 60-dB SPL contralateral noise during which listeners directed attention to the
      words; and (d) for the same SNR as in the 3rd condition, with words played
      backwards. RESULTS: There was greater suppression during active listening
      compared with passive listening that was apparent in the latency range of 6- to
      18-ms poststimulus onset. Ear differences in CEOAE amplitude were observed in all
      conditions, with right-ear amplitudes larger than those for the left. The
      absolute difference between CEOAE amplitude in quiet and with contralateral
      noise, a metric of suppression, was equivalent for right and left ears. When the
      amplitude differences were normalized, suppression was greater for noise
      presented to the right and the effect measured for a probe in the left ear.
      CONCLUSION: The findings support the theory that cortical mechanisms involved in
      listening to speech affect cochlear function through the MOC efferent system.

PMID- 21862679
TI  - A MEG investigation of single-word auditory comprehension in aphasia.
AB  - PURPOSE: To explore whether individuals with aphasia exhibit differences in the
      M350, an electrophysiological marker of lexical activation, compared with healthy
      controls. METHOD: Seven people with aphasia, 9 age-matched controls, and 10
      younger controls completed an auditory lexical decision task while cortical
      activity was recorded with magnetoencephalography. There were 2 stimulus
      conditions of interest: identity primed (i.e., a word preceded by itself) and
      semantic primed (i.e., a word preceded by a semantically related word). Latency
      and amplitude of the M350 response as well as reaction time were measured.
      RESULTS: Consistent with the age-matched control group, the group with aphasia
      showed both identity and semantic priming behaviorally. In contrast to the
      control groups, the group with aphasia did not show either semantic or identity
      priming of the M350 response. This group also demonstrated longer M350 latencies
      than either control group. Furthermore, within this group, M350 latency was
      positively correlated with a measure of semantic impairment. CONCLUSIONS: These
      findings highlight the usefulness of temporally sensitive measures when studying
      aphasia and demonstrate that the latency of electrophysiological markers is of
      interest in this population. In particular, increased M350 latency appears to be
      indicative of a semantic processing impairment.

PMID- 21862680
TI  - Auditory spectral integration in the perception of static vowels.
AB  - PURPOSE: To evaluate potential contributions of broadband spectral integration in
      the perception of static vowels. Specifically, can the auditory system infer
      formant frequency information from changes in the intensity weighting across
      harmonics when the formant itself is missing? Does this type of integration
      produce the same results in the lower (first formant [F1]) and higher (second
      formant [F2]) regions? Does the spacing between the spectral components affect a
      listener's ability to integrate the acoustic cues? METHOD: Twenty young listeners
      with normal hearing identified synthesized vowel-like stimuli created for
      adjustments in the F1 region (/Lambda/-/alpha/, /i/-/epsilon/) and in the F2
      region (/Lambda/-/ae/). There were 2 types of stimuli: (a) 2-formant tokens and
      (b) tokens in which 1 formant was removed and 2 pairs of sine waves were inserted
      below and above the missing formant; the intensities of these harmonics were
      modified to cause variations in their spectral center of gravity (COG). The COG
      effects were tested over a wide range of frequencies. RESULTS: Obtained patterns
      were consistent with calculated changes to the spectral COG, in both the F1 and
      F2 regions. The spacing of the sine waves did not affect listeners' responses.
      CONCLUSION: The auditory system may perform broadband integration as a type of
      auditory wideband spectral analysis.

PMID- 21862683
TI  - Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients
      treated with first-line gemcitabine-based chemotherapy.
AB  - Although erlotinib has become an important therapeutic option in addition to
      gemcitabine, the high frequency of KRAS mutations in pancreatic cancer probably
      limits the benefits. We retrospectively studied 136 pancreatic cancer patients
      with available formalin-fixed paraffin-embedded tumor blocks from 2003 to 2009 to
      understand the clinical significance of KRAS mutations in pancreatic cancer
      patients treated with gemcitabine-based chemotherapy. KRAS mutations were
      analyzed by sequencing codons 12, 13, and 61. In this study, 71 (52.2%) of the
      136 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n
      = 70) and 61 (n = 1) of KRAS. KRAS mutation was not associated with
      clinicopathologic parameters. Patients with KRAS mutations showed a worse
      response (11.3%) than those with wild-type KRAS (26.2%) and poor survival (mutant
      KRAS, 5.8 months vs. wild-type KRAS, 8.0 months; P = 0.001). Multivariate
      analysis revealed good prognostic factors for overall survival as well to
      moderately differentiated histology (P < 0.001; HR = 0.437, 95% CI: 0.301-0.634),
      locally advanced disease (P < 0.001; HR = 0.417, 95% CI: 0.255-0.681), response
      to first-line chemotherapy (P = 0.003; HR = 0.482, 95% CI: 0.297-0.780), and wild
      type KRAS (P = 0.001; HR = 0.523, 95% CI: 0.355-0.770). However, the observed
      survival advantage is derived from the subgroup of patients treated with
      gemcitabine/erlotinib (9.7 vs. 5.2 months; P = 0.002), whereas no survival
      difference based on KRAS mutation status is obvious in the other subgroup of
      patients treated without erlotinib (7.0 vs. 7.0 months; P = 0.121). These results
      need to be further explored in upcoming prospective studies to provide a
      rationale for personalized medicine in pancreatic cancer.

PMID- 21862684
TI  - Targeting the intracellular MUC1 C-terminal domain inhibits proliferation and
      estrogen receptor transcriptional activity in lung adenocarcinoma cells.
AB  - Mucin 1 (MUC1) is a diagnostic factor and therapy target in lung adenocarcinoma.
      MUC1 C-terminal intracellular domain (CD) interacts with estrogen receptor (ER)
      alpha and increases gene transcription in breast cancer cells. Because lung
      adenocarcinoma cells express functional ERalpha and ERbeta, we examined MUC1
      expression and MUC1-ER interaction. Because blocking MUC1 CD with an inhibitory
      peptide (PMIP) inhibited breast tumor growth, we tested whether PMIP would
      inhibit lung adenocarcinoma cell proliferation. We report that MUC1 interacts
      with ERalpha and ERbeta within the nucleus of H1793 lung adenocarcinoma cells in
      accordance with MUC1 expression. PMIP was taken up by H23 and H1793 cells and
      inhibited the proliferation of H1793, but not H23 cells, concordant with higher
      MUC1 protein expression in H1793 cells. Lower MUC1 protein expression in H23 does
      not correspond to microRNAs miR-125b and miR-145 that have been reported to
      reduce MUC1 expression. PMIP had no effect on the viability of normal human
      bronchial epithelial cells, which lack MUC1 expression. PMIP inhibited estradiol
      activated reporter gene transcription and endogenous cyclin D1 and nuclear
      respiratory factor-1 gene transcription in H1793 cells. These results indicate
      MUC1-ER functional interaction in lung adenocarcinoma cells and that inhibiting
      MUC1 inhibits lung adenocarcinoma cell viability.

PMID- 21862682
TI  - Immunological applications of stem cells in type 1 diabetes.
AB  - Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible
      number of patients insulin-independent. In this review, we revisit the role of
      stem cell (SC)-based applications in curing T1D. The optimal therapeutic approach
      for T1D should ideally preserve the remaining beta-cells, restore beta-cell
      function, and protect the replaced insulin-producing cells from autoimmunity. SCs
      possess immunological and regenerative properties that could be harnessed to
      improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance
      toward beta-cells through reshaping of the immune response and inhibition of
      autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are
      capable of engrafting and reversing hyperglycemia in mice. Bone marrow
      mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of
      immunomodulatory capabilities, they have been shown to cure newly diabetic
      nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two
      clinical trials. Cord blood SCs have been shown to facilitate the generation of
      regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients
      treated with cord blood SCs also did not show any adverse reaction in the absence
      of major effects on glycometabolic control. Although hematopoietic SCs rarely
      revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory
      properties in humans; newly hyperglycemic T1D patients have been successfully
      reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC
      transplantation. Finally, embryonic SCs also offer exciting prospects because
      they are able to generate glucose-responsive insulin-producing cells. Easy
      enthusiasm should be mitigated mainly because of the potential oncogenicity of
      SCs.

PMID- 21862686
TI  - Multiple-test assessment of devices to protect healthcare workers when
      administering cytotoxic drugs to patients.
AB  - PURPOSE: Evaluation of containment safety devices designed and introduced to
      protect preparers and administrators of hazardous drugs, through a multiple-test
      assessment. METHODS: Six devices were compared: (1) Kis1 gravity-fed infusion set
      (Doran International, France), (2) Tevadaptor Spike Port Adapter (Teva Pharma AG,
      France), (3) Phaseal Infusion Adapter C100 (Carmel Pharma AB, France), (4) Codan
      Connect Z (Codan, France), (5) Pchimx with or without a cap (Doran International,
      France), and (6) Clave extension set 011-H1225 with or without Spiros (Hospira,
      France). Assessment of exposure to hazardous drugs was performed using quinine as
      fluorescent marker. Mechanical tests included tightness, tension tests, and
      estimation of the force required to connect the infusion device to the bag.
      Ergonomic tests were performed by six pharmaceutical technicians. Microbiological
      contamination was tested with media-fill, on connected bag. RESULTS: No cytotoxic
      contamination was detected when using Phaseal, Tevadaptor or the Clave extension
      set with Spiros, Pchimx with a cap or Connect Z devices. For mechanical tests,
      all devices complied with the norm. Microbiological growth was observed neither
      in bags nor in tubings. The ergonomic study revealed differences between the
      devices for potential cytotoxic contamination risk only, but not for handling.
      CONCLUSIONS: The use of containment safety devices offers improved handling
      conditions of hazardous compounds. As this study takes various selection criteria
      into account, its results offer assistance in choosing the most suitable device.

PMID- 21862687
TI  - Development and implementation of a method for characterizing clinical pharmacy
      interventions and medication use in a cancer center.
AB  - PURPOSE: Develop and implement a method to characterize clinical pharmacy
      activities and the associated medication use in a comprehensive cancer center. A
      standard characterization of clinical pharmacy services facilitates benchmarking
      and informs continuous development. METHODS: A set of quantifiable parameters to
      describe clinical pharmacy activities and the associated medication use was
      proposed and validated by peer review. For implementation, clinical pharmacy
      interventions for six clinical pharmacy services at the King Hussein Cancer
      Center in 2008 were prospectively documented and the numbers of patients and
      medications dispensed for the same period were obtained from the admission office
      and pharmacy database respectively. RESULTS: The method comprised four main
      aspects: (1) number of interventions, (2) type of interventions, (3) number of
      doses dispensed, and (4) the NNI which is the number of doses dispensed for one
      intervention to occur. A total of 8552 interventions were recorded for 37,784
      patient days. Interventions were highest in the pediatric oncology and ICU with
      2612 (31%) and 1867 (22%) respectively, followed by medical oncology 1563 (18%),
      BMT 998 (12%), palliative care 792 (9%), and surgery 720 (8%). Interventions per
      1000 patient days were: ICU 555, pediatric oncology 326, BMT 319, palliative care
      244, medical oncology 137, and surgery 83. Main intervention categories for all
      services: therapeutic 3055 (36%), safety 2195 (26%), quality assurance 2376
      (28%), and education-information 925 (10%). The number of doses dispensed per
      1000 patient days was: BMT 19,404, palliative care 17,272, ICU 12,290, medical
      oncology 13,182, pediatric oncology 12,093, and surgery 8976. Finally, NNI was as
      follows: ICU 22, pediatric oncology 39, BMT 60, palliative care 71, medical
      oncology 96, and surgery 109. CONCLUSION: A method for characterizing clinical
      pharmacy interventions and medication use was developed and used to compare
      different oncology clinical pharmacy services. Further work is warranted to
      refine and validate the parameters proposed.

PMID- 21862685
TI  - Targeting tumor-initiating cancer cells with dCD133KDEL shows impressive tumor
      reductions in a xenotransplant model of human head and neck cancer.
AB  - A novel anticancer agent was constructed by fusing a gene encoding the scFV that
      targets both glycosylated and unglycosylated forms of CD133 to a gene fragment
      encoding deimmunized PE38KDEL. The resulting fusion protein, dCD133KDEL, was
      studied to determine its ability to bind and kill tumor-initiating cells in vitro
      and in vivo. The anti-CD133 scFV selectively bound HEK293 cells transfected with
      the CD133 receptor gene. Time course viability studies showed that dCD133KDEL
      selectively inhibited NA-SCC and UMSCC-11B, 2 head and neck squamous cell
      carcinomas that contain a CD133 expressing subpopulation. Importantly, the drug
      did not inhibit the viability of hematopoietic lineages measured by long-term
      culture-initiating cell and colony-forming assays from sorted human CD34+
      progenitor cells. In addition to in vitro studies, in vivo tumor initiation
      experiments confirmed that CD133-sorted cells implanted into the flanks of nude
      mice grew faster and larger than unsorted cells. In contrast, cells that were
      pretreated with dCD133KDEL before implantation showed the slowest and lowest
      incidence of tumors. Furthermore, UMSCC-11B-luc tumors treated with multiple
      intratumoral injections of dCD133KDEL showed marked growth inhibition, leading to
      complete degradation of the tumors that was not observed with an irrelevant
      control-targeted toxin. Experiments in immunocompetent mice showed that toxin
      deimmunization resulted in a 90% reduction in circulating antitoxin levels. These
      studies show that dCD133KDEL is a novel anticancer agent effective at inhibiting
      cell proliferation, tumor initiation, and eliminating established tumors by
      targeting the CD133 subpopulation. This agent shows significant promise for
      potential development as a clinically useful therapy.

PMID- 21862688
TI  - Implementing relevance feedback in ligand-based virtual screening using Bayesian
      inference network.
AB  - Recently, the use of the Bayesian network as an alternative to existing tools for
      similarity-based virtual screening has received noticeable attention from
      researchers in the chemoinformatics field. The main aim of the Bayesian network
      model is to improve the retrieval effectiveness of similarity-based virtual
      screening. To this end, different models of the Bayesian network have been
      developed. In our previous works, the retrieval performance of the Bayesian
      network was observed to improve significantly when multiple reference structures
      or fragment weightings were used. In this article, the authors enhance the
      Bayesian inference network (BIN) using the relevance feedback information. In
      this approach, a few high-ranking structures of unknown activity were filtered
      from the outputs of BIN, based on a single active reference structure, to form a
      set of active reference structures. This set of active reference structures was
      used in two distinct techniques for carrying out such BIN searching: reweighting
      the fragments in the reference structures and group fusion techniques. Simulated
      virtual screening experiments with three MDL Drug Data Report data sets showed
      that the proposed techniques provide simple ways of enhancing the cost
      effectiveness of ligand-based virtual screening searches, especially for higher
      diversity data sets.

PMID- 21862681
TI  - The extended granin family: structure, function, and biomedical implications.
AB  - The chromogranins (chromogranin A and chromogranin B), secretogranins
      (secretogranin II and secretogranin III), and additional related proteins (7B2,
      NESP55, proSAAS, and VGF) that together comprise the granin family subserve
      essential roles in the regulated secretory pathway that is responsible for
      controlled delivery of peptides, hormones, neurotransmitters, and growth factors.
      Here we review the structure and function of granins and granin-derived peptides
      and expansive new genetic evidence, including recent single-nucleotide
      polymorphism mapping, genomic sequence comparisons, and analysis of transgenic
      and knockout mice, which together support an important and evolutionarily
      conserved role for these proteins in large dense-core vesicle biogenesis and
      regulated secretion. Recent data further indicate that their processed peptides
      function prominently in metabolic and glucose homeostasis, emotional behavior,
      pain pathways, and blood pressure modulation, suggesting future utility of
      granins and granin-derived peptides as novel disease biomarkers.

PMID- 21862689
TI  - Mechanism-based inactivation of human cytochrome P450 2B6 by clopidogrel:
      involvement of both covalent modification of cysteinyl residue 475 and loss of
      heme.
AB  - We have investigated the mechanisms by which clopidogrel inactivates human
      cytochrome P450 2B6 (CYP2B6) in a reconstituted system. It was found that
      clopidogrel and its thiolactone metabolite, 2-oxo-clopidogrel, both inactivate
      CYP2B6 in a time- and concentration-dependent manner. On the basis of
      k(inact)/K(I) ratios, clopidogrel is approximately 5 times more efficient than 2
      oxo-clopidogrel in inactivating CYP2B6. Analysis of the molecular mass of the
      CYP2B6 wild-type (WT) protein that had been inactivated by either clopidogrel or
      2-oxo-clopidogrel showed an increase in the mass of the protein by ~350 Da. This
      increase in the protein mass corresponds to the addition of the active metabolite
      of clopidogrel to CYP2B6. It is noteworthy that this adduct can be cleaved from
      the protein matrix by incubation with dithiothreitol, confirming that the active
      metabolite is linked to a cysteinyl residue of CYP2B6 via a disulfide bond.
      Peptide mapping of tryptic digests of the inactivated CYP2B6 using electrospray
      ionization liquid chromatography-tandem mass spectrometry identified Cys475 as
      the site of covalent modification by the active metabolite. This was further
      confirmed by the observation that mutation of Cys475 to a serine residue
      eliminates the formation of the protein adduct and prevents the C475S variant
      from mechanism-based inactivation by 2-oxo-clopidogrel. However, this mutation
      did not prevent the C475S variant from being inactivated by clopidogrel.
      Furthermore, inactivation of both CYP2B6 WT and C475S by clopidogrel, but not by
      2-oxo-clopidogrel, led to the loss of the heme, which accounts for most of the
      loss of the catalytic activity. Collectively, these results suggest that
      clopidogrel inactivates CYP2B6 primarily through destruction of the heme, whereas
      2-oxo-clopidogrel inactivates CYP2B6 through covalent modification of Cys475.

PMID- 21862690
TI  - Study of GPR81, the lactate receptor, from distant species identifies residues
      and motifs critical for GPR81 functions.
AB  - Receptors from distant species may have conserved functions despite significant
      differences in protein sequences. Whereas the noncritical residues are often
      changed in distant species, the amino acids critical in receptor functions are
      often conserved. Studying the conserved residues between receptors from distant
      species offers valuable information to probe the roles of residues in receptor
      function. We identified two zebrafish receptors (zGPR81-1 and zGPR81-2) that show
      approximately 60% identity to human GPR81, GPR109a, and GPR109b but respond only
      to l-lactate and not to the GPR109a ligands. Protein sequence comparison among
      zebrafish GPR81s, mammalian GPR81s, GPR109a, and GPR109b identified a common
      structure (six Cys residues at the extracellular domains that potentially form
      three disulfide bonds) in this subfamily of receptors. In addition, a number of
      residues conserved in all GPR81s but not in GPR109s have been identified.
      Furthermore, we identified a conserved motif, C165-E166-S167-F168, at the second
      extracellular loop of GPR81. Using site-directed mutagenesis, we showed that
      Arg71 at the transmembrane domain 2 is very critical for GPR81 function. In
      addition, we demonstrated that the C165-E166-S167-F168 motif at the second
      extracellular loop is critical for GPR81 function, and the conserved six Cys
      residues at the extracellular regions are necessary for GPR81 function. It is
      important to mention that for those residues important for GPR81 function, the
      corresponding residues or motifs in GPR109a are also critical for GPR109a
      function. These findings help us better understand the interaction between
      lactate and GPR81 and provide useful information for GPR81 ligand design.

PMID- 21862691
TI  - High-affinity peroxisome proliferator-activated receptor beta/delta-specific
      ligands with pure antagonistic or inverse agonistic properties.
AB  - Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is a
      ligand-regulated nuclear receptor with essential functions in metabolism and
      inflammation. We have synthesized a new derivative [methyl 3-(N-(4-(hexylamino)-2
      methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (ST247) structurally related to
      the published PPARbeta/delta inhibitory ligand methyl 3-(N-(2-methoxy-4
      (phenylamino)phenyl)sulfamoyl)thiophene-2-carboxylate (GSK0660). ST247 has a
      higher affinity to PPARbeta/delta than GSK0660, and at equimolar concentrations,
      it more efficiently 1) induces the interaction with corepressors both in vitro
      and in vivo, 2) inhibits the agonist-induced transcriptional activity of
      PPARbeta/delta, and 3) down-regulates basal level expression of the peroxisome
      proliferator responsive element-driven PPARbeta/delta target gene ANGPTL4. Methyl
      3-(N-(4-(tert-butylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (PT
      S58), another high-affinity derivative from our series, also efficiently inhibits
      agonist-induced transcriptional activation, but in contrast to ST247, it does not
      enhance the interaction of PPARbeta/delta with corepressors. PT-S58 rather
      prevents corepressor recruitment triggered by the inverse agonist ST247. These
      findings classify ST247 as an inverse agonist, whereas PT-S58 is the first pure
      PPARbeta/delta antagonist described to date. It is noteworthy that ST247 and PT
      S58 are also effective on PPRE-independent functions of PPARbeta/delta: in
      monocytic cells, both ligands modulate expression of the activation marker CCL2
      in the opposite direction as an established PPARbeta/delta agonist. The
      possibility to differentially modulate specific functions of PPARbeta/delta makes
      these novel compounds invaluable tools to advance our understanding of
      PPARbeta/delta biology.

PMID- 21862693
TI  - Production of ibuprofen acyl glucosides by human UGT2B7.
AB  - UDP-glycosyltransferases (UGTs) are an important group of enzymes that
      participate in phase II metabolism of xenobiotics and use the cofactor UDP
      glucuronic acid for the production of glucuronides. When acting on molecules
      bearing a carboxylic acid they can form acyl glucuronides, a group of metabolites
      that has gained significant interest in recent years because of concerns about
      their potential role in drug toxicity. In contrast, reports about the production
      of drug acyl glucosides (which might also display high reactivity) have been
      scarce. In this study, we discovered the formation of acyl glycoside metabolites
      of R- and S-ibuprofen (Ibu) by human liver microsomes supplied with the cofactor
      UDP-glucose. Subsequently, human UGT2B7*1 and UGT2B7*2 recombinantly expressed in
      fission yeast Schizosaccharomyces pombe could be shown to catalyze these
      reactions. Moreover, we could enhance the glucoside production rate in fission
      yeast by overexpressing the fission yeast gene SPCC1322.04, a potential UDP
      glucose pyrophosphorylase (UGPase), but not by overexpression of SPCC794.10, and
      therefore suggest to name this gene fyu1 for fission yeast UGPase1. It was
      interesting to note that pronounced differences between the two polymorphic
      UGT2B7 variants were observed with respect to acyl glucoside production. Finally,
      using the metabolic precursor [(13)C(6)]glucose, we demonstrated the production
      of stable isotope-labeled reference standards of Ibu acyl glucoside and Ibu acyl
      glucuronide by whole-cell biotransformation in fission yeast.

PMID- 21862692
TI  - Dietary 9-cis-beta,beta-carotene fails to rescue vision in mouse models of leber
      congenital amaurosis.
AB  - Synthetic 9-cis-stereoisomers of vitamin A (all-trans-retinol) are especially
      promising agents for the fight against blinding diseases. Several studies
      suggested that 9-cis-beta,beta-carotene (9-cis-BC), a natural and abundant beta
      carotene isomer in the diet, could be the precursor of 9-cis-retinoids and thus
      could have therapeutic applications. Here we showed that 9-cis-BC is metabolized
      both in vitro and in vivo by two types of mouse carotenoid oxygenases, beta,beta
      Carotene monooxygenase 1 (BCMO1), and beta,beta-carotene dioxygenase 2 (BCDO2).
      In the symmetric oxidative cleavage reaction at C15,C15' position by BCMO1, part
      of the 9-cis-double bond was isomerized to the all-trans-stereoisomer, yielding
      all-trans-retinal and 9-cis-retinal in a molar ratio of 3:1. The asymmetric
      cleaving enzyme BCDO2 preferentially removed the 9-cis-ring site at the C9,C10
      double bond from this substrate, providing an all-trans-beta-10'-apocarotenal
      product that can be further metabolized to all-trans-retinal by BCMO1. Studies in
      knockout mouse models confirmed that each carotenoid oxygenase can metabolize 9
      cis-BC. Therefore, treatment of mouse models of Leber congenital amaurosis with 9
      cis-BC and 9-cis-retinyl-acetate, a well established 9-cis-retinal precursor,
      showed that the cis-carotenoid was far less effective than the cis-retinoid in
      rescuing vision. Thus, our in vitro and in vivo studies revealed that 9-cis-BC is
      not a major source for mouse 9-cis-retinoid production but is mainly converted to
      all-trans-retinoids to support canonical vitamin A action.

PMID- 21862694
TI  - Bone morphogenetic protein 4 accelerates the establishment of bovine
      trophoblastic cell lines.
AB  - Trophoblastic cells play a crucial role in implantation and placentogenesis. A
      large proportion of the failures of conception in cows occur in the peri
      implantation period, which are known as early embryo losses. In exploring this
      critical phenomenon, trophoblastic cell lines can provide substantial
      information. Unfortunately, there are few cell lines for this purpose in cattle
      because of the difficulty of raising successive cell stock in the long term. In
      this study, 12 new cell lines were established using bone morphogenetic protein 4
      (BMP4). BMP4 stimulated embryonic cells to enter the trophoblastic cell lineage
      but there were no significant differences between intact and BMP4-treated groups.
      Only one out of 49 embryos developed trophoblastic cells in the intact group.
      Finally, 12 cell lines were maintained for around 30 passages, and they retained
      trophoblastic characteristics and expressed bovine trophoblastic genes: placental
      lactogen, interferon-tau, pregnancy-associated glycoprotein 1, and prolactin
      related protein 1. Although the gene expression patterns were different among
      cell lines and depended on the cells, there was no significant relationship
      between the expression intensities of genes and the treatment dose of BMP4. All
      of them expressed bovine POU domain class 5 transcription factor 1 and caudal
      type homeobox 2. The expression of these genes was confirmed by quantitative RT
      PCR and immunohistochemical detection. These results suggest that BMP4 is
      involved in the raising of trophoblast cell lines from early embryonic cells and
      the newly developed cell lines can provide different types of bovine
      trophoblastic cells with different cell lineages. This may constitute a
      significant new tool for the examination of trophoblastic differentiation.

PMID- 21862695
TI  - The effects of ergot and non-ergot-derived dopamine agonists in an experimental
      mouse model of endometriosis.
AB  - Implantation of a retrogradely shed endometrium during menstruation requires an
      adequate blood supply, which allows the growth of endometriotic lesions. This
      suggests that the development of endometriosis can be impaired by inhibiting
      angiogenesis. The growth of endometriotic foci is impaired by commercial
      oncological antiangiogenic drugs used to block vascular endothelial growth factor
      (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of
      established endometriosis lesions by exerting antiangiogenic effects through
      VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an
      increased incidence of cardiac valve regurgitation. To evaluate the potential
      usage of non-ergot-derived dopamine agonists for the treatment of human
      endometriosis, we compared the efficacy of quinagolide with that of Cb2 in
      preventing angiogenesis and vascularization in a heterologous mouse model of
      endometriosis. Nude mice whose peritoneum had been implanted with eutopic human
      endometrial fragments were treated with vehicle, 50  MUg/kg per day oral Cb2, or
      50 or 200  MUg/kg per day quinagolide during a 14-day period. At the end of the
      treatment period, the implants were excised in order to assess lesion size, cell
      proliferation, degree of vascularization, and angiogenic gene expression.
      Neoangiogenesis was inhibited and the size of active endometriotic lesions,
      cellular proliferation index, and angiogenic gene expression were significantly
      reduced by both dopamine agonists when compared with the placebo. Given that Cb2
      and quinagolide were equally effective in inhibiting angiogenesis and reducing
      lesion size, these experiments provide the rationale for pilot studies to explore
      the use of non-ergot-derived dopamine agonists for the treatment of endometriosis
      in humans.

PMID- 21862696
TI  - Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis,
      metabolism and nuclear receptor signaling.
AB  - Endocrine-disrupting chemicals (EDCs) are exogenous agents with the ability to
      interfere with processes regulated by endogenous hormones. One such process is
      female reproductive function. The major reproductive organ in the female is the
      ovary. Disruptions in ovarian processes by EDCs can lead to adverse outcomes such
      as anovulation, infertility, estrogen deficiency, and premature ovarian failure
      among others. This review summarizes the effects of EDCs on ovarian function by
      describing how they interfere with hormone signaling via two mechanisms: altering
      the availability of ovarian hormones, and altering binding and activity of the
      hormone at the receptor level. Among the chemicals covered are pesticides (e.g.
      dichlorodiphenyltrichloroethane and methoxychlor), plasticizers (e.g. bisphenol A
      and phthalates), dioxins, polychlorinated biphenyls, and polycyclic aromatic
      hydrocarbons (e.g. benzo[a]pyrene).

PMID- 21862697
TI  - The impact of inattention and emotional problems on cognitive control in primary
      school children.
AB  - OBJECTIVE: The present study investigated the predictive value of parent/teacher
      reports of inattention and emotional problems on cognitive control function in
      241 children in primary school. METHOD: Cognitive control was measured by
      functions of set-shifting and working memory as assessed by the Behavior Rating
      Inventory of Executive Function (BRIEF) and performance-based tests (i.e., Color
      Trail Test and Digit Span Test). Symptoms of inattention and emotional problems
      were measured with parent and teacher reports on Swanson Nolan and Pelham-IV
      questionnaire and Strengths and Difficulties Questionnaire, respectively.
      RESULTS: Clinical symptoms of inattention and emotional problems explained the
      children's performance on test measures. However, symptoms of inattention made a
      significant contribution on all the selected measures of cognitive control,
      whereas reports concerning emotional problems uniquely explained the variance on
      the Shift scale from the BRIEF. CONCLUSION: Valid information on cognitive
      control function in primary school children should thus include simultaneous
      information concerning problems of inattention and emotion.

PMID- 21862698
TI  - Cigarette smoking, obesity, physical activity, and alcohol use as predictors of
      chemoprevention adherence in the National Surgical Adjuvant Breast and Bowel
      Project P-1 Breast Cancer Prevention Trial.
AB  - The double-blind, prospective, National Surgical Adjuvant Breast and Bowel
      Project (NSABP) Breast Cancer Prevention Trial (BCPT) showed a 50% reduction in
      the risk of breast cancer for tamoxifen versus placebo, yet many women at risk of
      breast cancer do not adhere to the 5-year course. This first report of the rich
      BCPT drug adherence data examines predictors of adherence. Between June, 1992 and
      September, 1997 13,338 women at high risk of breast cancer were randomly assigned
      to 20 mg/d tamoxifen versus placebo; we analyzed the 11,064 enrolled more than 3
      years before trial unblinding. Primary endpoint was full drug adherence (100% of
      assigned pills per staff report, excluding protocol-required discontinuation) at
      1 and 36 months; secondary was adequate adherence (76%-100%). Protocol-specified
      multivariable logistic regression tested lifestyle factors, controlling for
      demographic and medical predictors. About 13% were current smokers; 60% were
      overweight/obese; 46% had moderate/heavy physical activity; 21%, 66%, 13% drank
      0, 0-1, 1+ drinks per day, respectively; 91% were adequately adherent at 1 month;
      and 79% were at 3 years. Alcohol use was associated with reduced full adherence
      at 1 month (P = 0.016; OR = 0.79 1+ vs. 0), as was college education (P <0.001;
      OR = 0.78 vs. high school); age (P < 0.001; OR = 1.4 age 60+) and per capita
      household annual income (P < 0.001; OR = 1.2 per $30,000) with increased
      adherence. Current smoking (P = 0.003; OR = 0.75), age (P = 0.024, OR = 1.1),
      college education (P = 0.037; OR = 1.4), tamoxifen assignment (P = 0.031; OR =
      0.84), and breast cancer risk (P <.001; OR = 1.5 high vs. low) predicted adequate
      adherence at 36 months. There were no significant associations with obesity or
      physical activity. Alcohol use and smoking might indicate a need for greater
      adherence support.

PMID- 21862699
TI  - Randomized clinical trials of self-management with Asian/Pacific Islanders.
AB  - Little has been reported in the literature about self-management strategies of
      chronic conditions in Asian and Pacific Islanders (APIs). The purpose of this
      systematic review was to investigate randomized clinical trials (RCTs) of self
      management strategies of chronic conditions in APIs. Twenty-one studies were
      included in the final review, published between 1997 and 2010. Initially, the
      Jadad Scoring of Quality of Reports of Randomized Clinical Trials (JSQRRC) was
      used to determine the quality of RCT studies. The researchers then did a
      systematic review of each of the RCTs based on the JSQRRC criteria. JSQRRC scores
      ranged from 8 to 12, M = 9.6. Descriptive analysis indicated cognitive behavioral
      interventions as an effective treatment methodology for APIs. The results
      underscore the importance of clarifying the methodological components and
      reporting of RCTs. Interventions appropriate for APIs using disaggregated ethnic
      groups are essential to determine specific cultural responses to treatments and
      outcomes.

PMID- 21862700
TI  - Fall prevention in hospitals: an integrative review.
AB  - This article summarizes research and draws overall conclusions from the body of
      literature on fall prevention interventions to provide nurse administrators with
      a basis for developing evidence-based fall prevention programs in the hospital
      setting. Data are obtained from published studies. Thirteen articles are
      retrieved that focused on fall interventions in the hospital setting. An analysis
      is performed based on levels of evidence using an integrative review process.
      Multifactoral fall prevention intervention programs that included fall-risk
      assessments, door/bed/patient fall-risk alerts, environmental and equipment
      modifications, staff and patient safety education, medication management targeted
      to specific types, and additional assistance with transfer and toileting
      demonstrate reduction in both falls and fall injuries in hospitalized patients.
      Hospitals need to reduce falls by using multifactoral fall prevention programs
      using evidence-based interventions to reduce falls and injuries.

PMID- 21862701
TI  - Mechanisms by which social support networks influence healthy aging among Thai
      community-dwelling elderly.
AB  - OBJECTIVE: To examine the relationships among family, friendship networks and
      supports, health-promoting behaviors, and healthy aging. METHOD: A sample of 469
      Thai elderly persons was recruited using multistage random sampling. A structural
      equation model based on Berkman's conceptual model was performed. RESULTS: Family
      networks did not directly influence health-promoting behaviors but rather had an
      indirect effect through family support. Friendship networks had both a
      significant direct effect on the elderly health-promoting behaviors and an
      indirect effect via friendship support. Interestingly, friendships had both
      direct and indirect influences on family support to the elderly. Health-promoting
      behaviors had a powerful influence on healthy aging and play a significant role
      in mediating the relationship between family and friendship supports and healthy
      aging. DISCUSSION: Findings demonstrate the importance of family and friendship
      roles on health-promoting behaviors and healthy aging. Intervention programs
      should be designed to include a collaborative approach involving family members
      and friends.

PMID- 21862703
TI  - Fluorescence image screening for chemical compounds modifying cholesterol
      metabolism and distribution.
AB  - An automated fluorescence microscopy assay using a nontoxic cholesterol binding
      protein,  toxin domain 4, (D4), was developed in order to identify chemical
      compounds modifying intracellular cholesterol metabolism and distribution. Using
      this method, we screened a library of 1,056 compounds and identified 35 compounds
      that decreased D4 binding to the cell surface. Among them, 8 compounds were
      already reported to alter the biosynthesis or the intracellular distribution of
      cholesterol. The remaining 27 hit compounds were further analyzed biochemically
      and histochemically. Cell staining with another fluorescent cholesterol probe,
      filipin, revealed that 17 compounds accumulated cholesterol in the late
      endosomes. Five compounds decreased cholesterol biosynthesis, and two compounds
      inhibited the binding of D4 to the membrane. This visual screening method, based
      on the cholesterol-specific probe D4 in combination with biochemical analyses, is
      a cell-based, sensitive technique for identifying new chemical compounds and
      modifying cholesterol distribution and metabolism. Furthermore, it is suitable
      for high-throughput analysis for drug discovery.

PMID- 21862704
TI  - Elucidation of the pathway to astaxanthin in the flowers of Adonis aestivalis.
AB  - A few species in the genus Adonis are the only land plants known to produce the
      valuable red ketocarotenoid astaxanthin in abundance. Here, we ascertain the
      pathway that leads from the beta-rings of beta-carotene, a carotenoid ubiquitous
      in plants, to the 3-hydroxy-4-keto-beta-rings of astaxanthin (3,3'-dihydroxy
      beta,beta-carotene-4,4'-dione) in the blood-red flowers of Adonis aestivalis, an
      ornamental and medicinal plant commonly known as summer pheasant's eye. Two gene
      products were found to catalyze three distinct reactions, with the first and
      third reactions of the pathway catalyzed by the same enzyme. The pathway
      commences with the activation of the number 4 carbon of a beta-ring in a reaction
      catalyzed by a carotenoid beta-ring 4-dehydrogenase (CBFD), continues with the
      further dehydrogenation of this carbon to yield a carbonyl in a reaction
      catalyzed by a carotenoid 4-hydroxy-beta-ring 4-dehydrogenase, and concludes with
      the addition of an hydroxyl group at the number 3 carbon in a reaction catalyzed
      by the erstwhile CBFD enzyme. The A. aestivalis pathway is both portable and
      robust, functioning efficiently in a simple bacterial host. Our elucidation of
      the pathway to astaxanthin in A. aestivalis provides enabling technology for
      development of a biological production process and reveals the evolutionary
      origin of this unusual plant pathway, one unrelated to and distinctly different
      from those used by bacteria, green algae, and fungi to synthesize astaxanthin.

PMID- 21862706
TI  - A surprising role for vacuolar pyrophosphatase.

PMID- 21862705
TI  - Physcomitrella cyclin-dependent kinase A links cell cycle reactivation to other
      cellular changes during reprogramming of leaf cells.
AB  - During regeneration, differentiated plant cells can be reprogrammed to produce
      stem cells, a process that requires coordination of cell cycle reactivation with
      acquisition of other cellular characteristics. However, the factors that
      coordinate the two functions during reprogramming have not been determined. Here,
      we report a link between cell cycle reactivation and the acquisition of new cell
      type characteristics through the activity of cyclin-dependent kinase A (CDKA)
      during reprogramming in the moss Physcomitrella patens. Excised gametophore leaf
      cells of P. patens are readily reprogrammed, initiate tip growth, and form
      chloronema apical cells with stem cell characteristics at their first cell
      division. We found that leaf cells facing the cut undergo CDK activation along
      with induction of a D-type cyclin, tip growth, and transcriptional activation of
      protonema-specific genes. A DNA synthesis inhibitor, aphidicolin, inhibited cell
      cycle progression but prevented neither tip growth nor protonemal gene
      expression, indicating that cell cycle progression is not required for
      acquisition of protonema cell-type characteristics. By contrast, treatment with a
      CDK inhibitor or induction of dominant-negative CDKA;1 protein inhibited not only
      cell cycle progression but also tip growth and protonemal gene expression. These
      findings indicate that cell cycle progression is coordinated with other cellular
      changes by the concomitant regulation through CDKA;1.

PMID- 21862702
TI  - Mechanisms and genetic determinants regulating sterol absorption, circulating LDL
      levels, and sterol elimination: implications for classification and disease risk.
AB  - This review integrates historical biochemical and modern genetic findings that
      underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias
      that bear on human disease. These range from life-threatening conditions of
      infancy through severe coronary heart disease of young adulthood, to indolent
      disorders of middle- and old-age. We particularly focus on the biological aspects
      of those gene mutations and variants that impact on sterol absorption and
      hepatobiliary excretion via specific membrane transporter systems (NPC1L1,
      ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized
      lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release
      into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL
      and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE,
      LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic
      data with biological processes have important implications for the classification
      of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias,
      sitosterolemia, and newly emerging phenotypes, as well as their management
      through both nutritional and pharmaceutical means.

PMID- 21862707
TI  - Keep an eye on PPi: the vacuolar-type H+-pyrophosphatase regulates
      postgerminative development in Arabidopsis.
AB  - Postgerminative growth of seed plants requires specialized metabolism, such as
      gluconeogenesis, to support heterotrophic growth of seedlings until the
      functional photosynthetic apparatus is established. Here, we show that the
      Arabidopsis thaliana fugu5 mutant, which we show to be defective in AVP1
      (vacuolar H(+)-pyrophosphatase), failed to support heterotrophic growth after
      germination. We found that exogenous supplementation of Suc or the specific
      removal of the cytosolic pyrophosphate (PPi) by the heterologous expression of
      the cytosolic inorganic pyrophosphatase1 (IPP1) gene from budding yeast
      (Saccharomyces cerevisiae) rescued fugu5 phenotypes. Furthermore, compared with
      the wild-type and AVP1(Pro):IPP1 transgenic lines, hypocotyl elongation in the
      fugu5 mutant was severely compromised in the dark but recovered upon exogenous
      supply of Suc to the growth media. Measurements revealed that the peroxisomal
      beta-oxidation activity, dry seed contents of storage lipids, and their
      mobilization were unaffected in fugu5. By contrast, fugu5 mutants contained ~2.5
      fold higher PPi and ~50% less Suc than the wild type. Together, these results
      provide clear evidence that gluconeogenesis is inhibited due to the elevated
      levels of cytosolic PPi. This study demonstrates that the hydrolysis of cytosolic
      PPi, rather than vacuolar acidification, is the major function of AVP1/FUGU5 in
      planta. Plant cells optimize their metabolic function by eliminating PPi in the
      cytosol for efficient postembryonic heterotrophic growth.

PMID- 21862708
TI  - Generation of signaling specificity in Arabidopsis by spatially restricted
      buffering of ligand-receptor interactions.
AB  - Core signaling pathways function in multiple programs during multicellular
      development. The mechanisms that compartmentalize pathway function or confer
      process specificity, however, remain largely unknown. In Arabidopsis thaliana,
      ERECTA (ER) family receptors have major roles in many growth and cell fate
      decisions. The ER family acts with receptor TOO MANY MOUTHS (TMM) and several
      ligands of the EPIDERMAL PATTERNING FACTOR LIKE (EPFL) family, which play
      distinct yet overlapping roles in patterning of epidermal stomata. Here, our
      examination of EPFL genes EPFL6/CHALLAH (CHAL), EPFL5/CHALLAH-LIKE1, and
      EPFL4/CHALLAH-LIKE2 (CLL2) reveals that this family may mediate additional ER
      dependent processes. chal cll2 mutants display growth phenotypes characteristic
      of er mutants, and genetic interactions are consistent with CHAL family molecules
      acting as ER family ligands. We propose that different classes of EPFL genes
      regulate different aspects of ER family function and introduce a TMM-based
      discriminatory mechanism that permits simultaneous, yet compartmentalized and
      distinct, function of the ER family receptors in growth and epidermal patterning.

PMID- 21862709
TI  - BIK1 function in plant growth and defense signaling.

PMID- 21862711
TI  - Bivalirudin for anticoagulation during hypothermic cardiopulmonary bypass and
      recombinant factor VIIa for iatrogenic coagulopathy.
AB  - OBJECTIVE: To describe management of anticoagulation with a decreased dose
      requirement of bivalirudin during cardiopulmonary bypass using deep hypothermic
      circulatory arrest (DHCA) and the reversal of the ensuing coagulopathy with
      recombinant factor VIIa (rFVIIa). CASE SUMMARY: A 48-year-old male developed
      chest pain, hypertension, and an aortic aneurysm requiring urgent surgical
      repair. At the time of surgery, the patient reported an allergy to heparin, so
      bivalirudin was used for anticoagulation (1 mg/kg loading dose, followed by
      intermittent infusions of 1.25-2.5 mg/kg/h over the 5 hours of cardiopulmonary
      bypass). When the cooling process was initiated, bivalirudin was stopped in
      anticipation of loss of the clotting cascade function and potential slowing of
      drug elimination. Bivalirudin was restarted for 45 minutes during the rewarming
      period because of concern for potential clot formation in the bypass circuit with
      recovery of hemostasis; it was again stopped due to the patient's activated
      clotting time (ACT) of 504 seconds. Despite this measure, diffuse and severe
      coagulopathy was observed upon rewarming, with ACTs longer than 999 seconds.
      Although multiple blood products were administered, visualization of a clot in
      the surgical field was not notable. A total dose of rFVIIa 20 MUg/kg was
      administered, resulting in visual clot formation within 4 minutes. On
      postsurgical day 6, bilateral asymptomatic distal deep vein thromboses were noted
      on imaging; on postsurgical day 8, fondaparinux 2.5 mg subcutaneously was
      administered daily to prevent clot extension. The patient was discharged on
      postoperative day 23 with no acute issues and no further anticoagulants.
      DISCUSSION: Alternative anticoagulation agents such as bivalirudin are used in
      patients who have an allergy or contraindication to heparin. We propose that
      prolonged coagulopathy after the induction of hypothermia is due to decreased
      clotting cascade function as well as slowing of protease activity resulting in
      decreased bivalirudin elimination. We observed a positive response to low-dose
      rFVIIa, which could be due to activation of the extrinsic pathway and/or a
      thrombin burst, resulting in hemostasis. Currently, there is limited evidence
      supporting reversal of direct thrombin inhibitors with rFVIIa. CONCLUSIONS: In
      the setting of DHCA, bivalirudin should be used cautiously, with frequent
      monitoring of the ACTs and potential cessation of the infusion in anticipation of
      prolonged drug effect with subsequent potential coagulopathy. If coagulopathy
      ensues, use of low-dose rFVIIa may be an option to initiate hemostasis. When
      using rFVIIa, it is important to consider the risk of thrombosis and monitor
      patients accordingly.

PMID- 21862710
TI  - Biochemical and genetic requirements for function of the immune response
      regulator BOTRYTIS-INDUCED KINASE1 in plant growth, ethylene signaling, and PAMP
      triggered immunity in Arabidopsis.
AB  - Arabidopsis thaliana BOTRYTIS-INDUCED KINASE1 (BIK1) regulates immune responses
      to a distinct class of pathogens. Here, mechanisms underlying BIK1 function and
      its interactions with other immune response regulators were determined. We
      describe BIK1 function as a component of ethylene (ET) signaling and PAMP
      triggered immunity (PTI) to fungal pathogens. BIK1 in vivo kinase activity
      increases in response to flagellin peptide (flg22) and the ET precursor 1
      aminocyclopropane-1-carboxylic acid (ACC) but is blocked by inhibition of ET
      perception. BIK1 induction by flg22, ACC, and pathogens is strictly dependent on
      EIN3, and the bik1 mutation results in altered expression of ET-regulated genes.
      BIK1 site-directed mutants were used to determine residues essential for
      phosphorylation and biological functions in planta, including PTI, ET signaling,
      and plant growth. Genetic analysis revealed flg22-induced PTI to Botrytis cinerea
      requires BIK1, EIN2, and HUB1 but not genes involved in salicylate (SA)
      functions. BIK1-mediated PTI to Pseudomonas syringae is modulated by SA, ET, and
      jasmonate signaling. The coi1 mutation suppressed several bik1 phenotypes,
      suggesting that COI1 may act as a repressor of BIK1 function. Thus, common and
      distinct mechanisms underlying BIK1 function in mediating responses to distinct
      pathogens are uncovered. In sum, the critical role of BIK1 in plant immune
      responses hinges upon phosphorylation, its function in ET signaling, and complex
      interactions with other immune response regulators.

PMID- 21862712
TI  - Comment: assessment of vancomycin dosing and subsequent serum concentrations in
      pediatric patients.

PMID- 21862713
TI  - Montelukast for symptom control of interstitial cystitis.
AB  - OBJECTIVE: To describe the effects of montelukast, a leukotriene receptor
      antagonist commonly used in the treatment of allergic rhinitis and asthma, on the
      symptoms of interstitial cystitis (IC). CASE SUMMARY: A 64-year-old male had a
      history of IC with previous trials of solifenacin, dutasteride, and tamsulosin
      and little improvement in IC symptom reduction. When montelukast 10 mg was
      initiated for allergic rhinitis symptoms, a substantial improvement in urinary
      urgency and pain during therapy was noted. This improvement subsequently
      disappeared when montelukast was stopped. DISCUSSION: IC, a rare occurrence in
      the male population, is related to an inflammatory process and has also been
      associated with inappropriate leukotriene release, which is the target of
      montelukast therapy. In general, treatment for IC includes systemic medical
      therapy, local bladder treatment, surgical and neurosurgical procedures, and
      intravesical drug installation. Currently, montelukast is Food and Drug
      Administration approved for use in the treatment and prevention of mild-to
      moderate asthma and exercise-induced asthma, as well as treatment of seasonal and
      perennial allergic rhinitis. While montelukast treatment did not cure the
      patient's IC, it improved his quality of life through substantial symptomatic
      relief, including less pain and urgency. CONCLUSIONS: Montelukast may be an
      effective treatment option in the management of interstitial cystitis. Further
      research is needed to substantiate this novel use.

PMID- 21862714
TI  - Single-agent, broad-spectrum fluoroquinolones for the outpatient treatment of low
      risk febrile neutropenia.
AB  - OBJECTIVE: To evaluate the use of oral, single-agent, broad-spectrum
      fluoroquinolones in the treatment of low-risk febrile neutropenia (FN). DATA
      SOURCES: MEDLINE via Ovid (1948 to May, week 3, 2011) and EMBASE (1980 to 2011,
      week 21) were searched using the terms febrile neutropenia, fluoroquinolone,
      quinolone derivative, levofloxacin, moxifloxacin, and neoplasm. References of
      selected articles, review articles, and treatment guidelines were reviewed. STUDY
      SELECTION AND DATA EXTRACTION: Trials evaluating the efficacy of oral, single
      agent, broad-spectrum fluoroquinolones in the treatment of chemotherapy-induced
      FN were included if the majority of patients in the study had low-risk FN. Trials
      involving pediatric patients, non-Food and Drug Administration-approved
      fluoroquinolones, or monotherapy with ciprofloxacin or ofloxacin were excluded.
      Data extracted included study design, patient demographics, antiinfective
      regimens, and treatment outcomes. DATA SYNTHESIS: Four clinical trials were
      included. One trial compared levofloxacin with piperacillin/tazobactam with a
      success rate (afebrile at 72 hours) of 76.5% in the levofloxacin group compared
      with 88.3% in the piperacillin/tazobactam group. This trial was not limited to
      low-risk patients. The remaining 3 trials investigated moxifloxacin monotherapy
      in low-risk patients. Two of these were noncontrolled trials with success rates
      (afebrile at 5 days) of 91% and 95%. The final trial randomized patients to
      moxifloxacin or ceftriaxone and had success rates (hospital discharge at 48
      hours) of 79.2% and 73.9%, respectively. In all 4 trials, treatment of FN with
      levofloxacin or moxifloxacin was deemed to be safe and effective. Although all
      studies had positive results, they were limited by small sample sizes and the
      absence of universal use of control comparisons. CONCLUSIONS: Use of oral, single
      agent, broad-spectrum fluoroquinolones for outpatient treatment of FN in low-risk
      patients has shown promising results. At this time, this type of therapy should
      be limited to low-risk patients. Future clinical trials should include larger
      sample sizes and a comparison with existing first-line oral therapy-oral
      ciprofloxacin plus amoxicillin/clavulanate.

PMID- 21862715
TI  - Cutaneous recall phenomenon with vinorelbine.

PMID- 21862716
TI  - Innovation in health care: a call to action.
AB  - Innovation in health care is difficult yet necessary in this era of health care
      delivery and payment reform. The Center for Medicare and Medicaid Services (CMS)
      Innovation Center and the CMS Partnership for Patients have announced priority
      areas to achieve better health, better care, and reduced costs through continuous
      improvement. Pharmacists possess the therapeutic knowledge and medication process
      expertise to create collaborative and innovative solutions that address
      medication use and safety problems. As a profession, we face a call to action. As
      pharmacy practitioners, educators, and researchers, we face an unprecedented
      opportunity to make a difference. So, either individually or collectively in our
      workplaces and pharmacist professional organizations, we must respond to this
      call to action. Some practical suggestions are offered to get us started on this
      journey.

PMID- 21862717
TI  - Inpatient and outpatient occurrence of deep vein thrombosis and pulmonary
      embolism and thromboprophylaxis following selected at-risk surgeries.
AB  - BACKGROUND: Despite evidence-based guidelines on prevention, many surgical
      patients remain at risk of deep vein thrombosis (DVT) and pulmonary embolism
      (PE). OBJECTIVE: To quantify the provision of thromboprophylaxis and proportion
      of US surgical patients who develop DVT/PE, both in the hospital and
      postdischarge. METHODS: This study was an observational, retrospective database
      analysis of national managed care data. Data were extracted from the Premier
      Perspective-i3 Pharma Informatics linked database on patients hospitalized
      between January 2005 and November 2007 for orthopedic surgery or major abdominal
      surgery. Patients were included if they were aged 18 years or older at the time
      of hospitalization and had at least 6 months of continuous plan enrollment prior
      to index hospitalization. Patients discharged to an acute care facility or with
      atrial fibrillation were excluded. Prophylaxis status was evaluated during index
      hospitalization and for 14 days postdischarge. The proportion of patients who
      developed DVT/PE was calculated during index hospitalization and for 30 days
      postdischarge. RESULTS: The analysis included 19,581 patients following major
      abdominal surgery and 5315 patients following orthopedic surgery. Inpatient
      pharmacologic or mechanical thromboprophylaxis was received by 58.7% of abdominal
      surgery patients and 85.0% of orthopedic surgery patients; outpatient
      pharmacologic prophylaxis was received by 1.6% and 58.4% of patients,
      respectively. Total mean (SD) prophylaxis duration was 1.7 (3.7) days following
      abdominal surgery and 13.0 (11.6) days following orthopedic surgery. The
      proportion of abdominal surgery patients who developed symptomatic DVT/PE was
      1.6%; 3.1% of orthopedic surgery patients developed symptomatic DVT/PE, with
      almost 40% of the events occurring postdischarge. CONCLUSIONS: Continued efforts
      are needed to prevent DVT/PE after abdominal and orthopedic surgery. Initiatives
      that encourage outpatient prophylaxis must ensure that appropriate prophylaxis of
      adequate duration is prescribed to all at-risk surgical patients to further
      reduce DVT/PE across the continuum of care. Pharmacists can play an important
      role in optimizing continuity of patient care in the prevention of DVT, in
      providing anticoagulation services that can help reduce the incidence of DVT/PE
      and bleeding complications, and in helping hospitals achieve performance
      measures.

PMID- 21862718
TI  - Age- and sex-specific trends in the incidence of hospitalized acute coronary
      syndromes in Western Australia.
AB  - BACKGROUND- The incidence of myocardial infarction has declined during the past 4
      decades in many populations. However, there are limited population data measuring
      trends in acute coronary syndromes (ACS). We therefore examined temporal trends
      in the incidence of hospitalized ACS by age and sex in a population-based cohort.
      METHODS AND RESULTS- The Western Australian Data Linkage System, a repository of
      linked administrative health data, was used to identify 29 421 incident ACS
      hospitalizations between 1996 and 2007. Poisson log-linear regression models were
      used to calculate incidence rate changes. Age-standardized incidence rates of ACS
      declined annually in men by 1.7% (95% confidence interval [CI], -2.1 to -1.3) and
      in women by 1.6% (95% CI, -2.1 to -1.0). These declining rates were underpinned
      by annual reductions in the incidence of unstable angina (men, -3.0%; 95% CI, 
      3.7 to -2.4; women, -2.5; 95% CI, -3.3 to -1.7), whereas annual changes in
      myocardial infarction incidence were less (men, -1.0%; 95% CI, -1.5 to -0.5;
      women, -0.8%; 95% CI, -1.6 to 0). However, the overall trends masked age group
      differences, with ACS incidence increasing annually in 35- to 54-year-old women
      (2.3%; 95% CI, 1.0 to 3.8), predominantly driven by increasing incidence of
      myocardial infarction. CONCLUSIONS- The age-standardized incidence of ACS
      decreased significantly in Western Australia from 1996 to 2007. However, an
      increase in ACS incidence in women ages 35 to 54 years is troubling and warrants
      further investigation.

PMID- 21862719
TI  - Use of hundreds of electrocardiographic biomarkers for prediction of mortality in
      postmenopausal women: the Women's Health Initiative.
AB  - BACKGROUND- Simultaneous contribution of hundreds of electrocardiographic (ECG)
      biomarkers to prediction of long-term mortality in postmenopausal women with
      clinically normal resting ECGs is unknown. METHODS AND RESULTS- We analyzed ECGs
      and all-cause mortality in 33 144 women enrolled in the Women's Health Initiative
      trials who were without baseline cardiovascular disease or cancer and had normal
      ECGs by Minnesota and Novacode criteria. Four hundred and seventy-seven ECG
      biomarkers, encompassing global and individual ECG findings, were measured with
      computer algorithms. During a median follow-up of 8.1 years (range for survivors,
      0.5 to 11.2 years), 1229 women died. For analyses, the cohort was randomly split
      into derivation (n=22 096; deaths, 819) and validation (n=11 048; deaths, 410)
      subsets. ECG biomarkers and demographic and clinical characteristics were
      simultaneously analyzed using both traditional Cox regression and random survival
      forest, a novel algorithmic machine-learning approach. Regression modeling failed
      to converge. Random survival forest variable selection yielded 20 variables that
      were independently predictive of long-term mortality, 14 of which were ECG
      biomarkers related to autonomic tone, atrial conduction, and ventricular
      depolarization and repolarization. CONCLUSIONS- We identified 14 ECG biomarkers
      from among hundreds that were associated with long-term prognosis using a novel
      random forest variable selection methodology. These biomarkers were related to
      autonomic tone, atrial conduction, ventricular depolarization, and ventricular
      repolarization. Quantitative ECG biomarkers have prognostic importance and may be
      markers of subclinical disease in apparently healthy postmenopausal women.

PMID- 21862720
TI  - Accuracy and prognostic value of American Heart Association: recommended
      depression screening in patients with coronary heart disease: data from the Heart
      and Soul Study.
AB  - BACKGROUND- In 2008, the American Heart Association (AHA) recommended a 2-step
      screening method, consisting of the 2-item Patient Health Questionnaire (PHQ-2)
      followed by the 9-item Patient Health Questionnaire (PHQ-9), for identifying
      depression in cardiovascular patients. The accuracy and prognostic value of this
      screening method have not been evaluated. METHODS AND RESULTS- We administered
      the 2-step AHA-recommended screening algorithm to 1024 patients with stable
      coronary heart disease and calculated sensitivity and specificity against a gold
      standard interview for major depressive disorder. Subsequent cardiovascular
      events (myocardial infarction, stroke, transient ischemic attack, heart failure,
      or death) were determined during a mean of 6.27 +/- 2.11 years of follow-up. The
      AHA-recommended screening method had high specificity (0.91; 95% confidence
      interval, 0.89 to 0.93) but low sensitivity (0.52; 95% confidence interval, 0.46
      to 0.59) for a diagnosis of major depressive disorder. Participants who screened
      positive on the AHA depression protocol had a 55% greater risk of events than
      those who screened negative (age-adjusted hazard ratio, 1.55; 95% confidence
      interval, 1.21 to 1.97; P=0.0005). After adjustment for age, sex, body mass
      index, history of myocardial infarction, hypertension, diabetes, heart failure,
      and high-density lipoprotein levels, screening positive remained associated with
      a 41% greater rate of cardiovascular events (hazard ratio, 1.41; 95% confidence
      interval, 1.10 to 1.81; P=0.008). CONCLUSIONS- Among outpatients with stable
      coronary heart disease, the AHA-recommended depression screening protocol is
      highly specific for depression and identifies patients at risk for adverse
      cardiovascular outcomes.

PMID- 21862721
TI  - Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in
      mice fed a high-fat diet.
AB  - Systemic inflammation is strongly involved in the pathophysiology of the
      metabolic syndrome, a cluster of metabolic risk factors that includes
      hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF
      kappaB activity but also reduces hypertriglyceridemia in humans. The aim of this
      study was to investigate the mechanism by which aspirin improves
      hypertriglyceridemia. Human apolipoprotein CI (apoCI)-expressing mice (APOC1
      mice), an animal model with elevated plasma triglyceride (TG) levels, as well as
      normolipidemic wild-type (WT) mice were fed a high-fat diet (HFD) and treated
      with aspirin. Aspirin treatment reduced hepatic NF-kappaB activity in HFD-fed
      APOC1 and WT mice, and in addition, aspirin decreased plasma TG levels (-32%, P <
      0.05) in hypertriglyceridemic APOC1 mice. This TG-lowering effect could not be
      explained by enhanced VLDL-TG clearance, but aspirin selectively reduced hepatic
      production of VLDL-TG in both APOC1 (-28%, P < 0.05) and WT mice (-33%, P < 0.05)
      without affecting VLDL-apoB production. Aspirin did not alter hepatic expression
      of genes involved in FA oxidation, lipogenesis, and VLDL production but decreased
      the incorporation of plasma-derived FA by the liver into VLDL-TG (-24%, P <
      0.05), which was independent of hepatic expression of genes involved in FA uptake
      and transport. We conclude that aspirin improves hypertriglyceridemia by
      decreasing VLDL-TG production without affecting VLDL particle production.
      Therefore, the inhibition of inflammatory pathways by aspirin could be an
      interesting target for the treatment of hypertriglyceridemia.

PMID- 21862722
TI  - Insulin-like growth factor as a novel stimulator for somatolactin secretion and
      synthesis in carp pituitary cells via activation of MAPK cascades.
AB  - Somatolactin (SL), a member of the growth hormone/prolactin family, is a
      pituitary hormone unique to fish models. Although SL is known to have diverse
      functions in fish, the mechanisms regulating its secretion and synthesis have not
      been fully characterized. Using grass carp pituitary cells as a model, here we
      examined the role of insulin-like growth factor (IGF) in SL regulation at the
      pituitary level. As a first step, the antisera for the two SL isoforms expressed
      in the carp pituitary, SLalpha and SLbeta, were produced, and their specificity
      was confirmed by antiserum preabsorption and immunohistochemical staining in the
      carp pituitary. Western blot using these antisera revealed that grass carp
      SLalpha and SLbeta could be N-linked glycosylated and their basal secretion and
      cell content in carp pituitary cells could be elevated by IGF-I and -II
      treatment. These stimulatory effects occurred with parallel rises in SLalpha and
      SLbeta mRNA levels, and these SL gene expression responses were not mimicked by
      insulin but blocked by IGF-I receptor inactivation. In carp pituitary cells, IGF
      I and -II could induce rapid phosphorylation of IGF-I receptor, MEK1/2, ERK1/2,
      MKK3/6, and p38 MAPK; and SLalpha and SLbeta secretion, protein production, and
      mRNA expression caused by IGF-I and -II stimulation were negated by inactivating
      MEK1/2 and p38 MAPK. Parallel inhibition of PI3K and Akt, however, were not
      effective in these regards. These results, taken together, provide evidence that
      IGF can upregulate SL secretion and synthesis at the pituitary level via
      stimulation of MAPK- but not PI3K/Akt-dependent pathways.

PMID- 21862723
TI  - Hyperglucagonemia precedes a decline in insulin secretion and causes
      hyperglycemia in chronically glucose-infused rats.
AB  - Islet damage from glucose toxicity is implicated in the pathogenesis of type 2
      diabetes, but the sequence of events leading to islet cell dysfunction and
      hyperglycemia remains unclear. To examine the early stages of islet pathology
      resulting from increased basal glucose loads, normal awake rats were infused with
      glucose continuously for 10 days. Plasma glucose and markers of islet and liver
      function were monitored throughout the infusion. After initial hyperglycemia,
      rats adapted to the infusion and maintained euglycemia for approximately 4 days.
      Continued infusion led to worsening hyperglycemia in just 5% of rats after 6
      days, but 69% after 8 days and 89% after 10 days, despite unchanged basal and
      stimulated plasma insulin and C-peptide concentrations. In contrast, plasma
      glucagon concentrations increased fivefold. Endogenous glucose production (EGP)
      was appropriately suppressed after 4 days (2.8 +/- 0.7 vs. 6.1 +/- 0.4 mg.kg(
      1).min(-1) on day 0, P < 0.001) but tripled between days 4 and 8 (9.9 +/- 1.7
      mg.kg(-1).min(-1), P < 0.01). Surprisingly, the increase in EGP was accompanied
      by increased mitochondrial phosphoenolpyruvate carboxykinase expression with
      appropriate suppression of the cytosolic isoform. Infusion of anti-glucagon
      antibodies normalized plasma glucose to levels identical to those on day 4 and
      ~300 mg/dl lower than controls. This improved glycemia was associated with a 60%
      reduction in EGP. These data support the novel concept that glucose toxicity may
      first manifest as alpha-cell dysfunction prior to any measurable deficit in
      insulin secretion. Such hyperglucagonemia could lead to excessive glucose
      production overwhelming the capacity of the beta-cell to maintain glucose
      homeostasis.

PMID- 21862724
TI  - Mitochondrial dysfunction and insulin resistance from the outside in:
      extracellular matrix, the cytoskeleton, and mitochondria.
AB  - Insulin resistance in skeletal muscle is a prominent feature of obesity and type
      2 diabetes. The association between mitochondrial changes and insulin resistance
      is well known. More recently, there is growing evidence of a relationship between
      inflammation, extracellular remodeling, and insulin resistance. The intent of
      this review is to propose a potentially novel mechanism for the development of
      insulin resistance, focusing on the underappreciated connections among
      inflammation, extracellular remodeling, cytoskeletal interactions, mitochondrial
      function, and insulin resistance in human skeletal muscle. Several sources of
      inflammation, including expansion of adipose tissue resulting in increased
      lipolysis and alterations in pro- and anti-inflammatory cytokines, contribute to
      the insulin resistance observed in obesity and type 2 diabetes. In the
      experimental model of lipid oversupply, an inflammatory response in skeletal
      muscle leads to altered expression extracellular matrix-related genes as well as
      nuclear encoded mitochondrial genes. A similar pattern also is observed in
      "naturally" occurring insulin resistance in muscle of obese nondiabetic
      individuals and patients with type 2 diabetes mellitus. More recently,
      alterations in proteins (including alpha-actinin-2, desmin, proteasomes, and
      chaperones) involved in muscle structure and function have been observed in
      insulin-resistant muscle. Some of these cytoskeletal proteins are mechanosignal
      transducers that allow muscle fibers to sense contractile activity and respond
      appropriately. The ensuing alterations in expression of genes coding for
      mitochondrial proteins and cytoskeletal proteins may contribute to the
      mitochondrial changes observed in insulin-resistant muscle. These changes in turn
      may lead to a reduction in fat oxidation and an increase in intramyocellular
      lipid, which contributes to the defects in insulin signaling in insulin
      resistance.

PMID- 21862725
TI  - Central angiotensin II has catabolic action at white and brown adipose tissue.
AB  - Considerable evidence implicates the renin-angiotensin system (RAS) in the
      regulation of energy balance. To evaluate the role of the RAS in the central
      nervous system regulation of energy balance, we used osmotic minipumps to
      chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to
      adult male Long-Evans rats, resulting in reduced food intake, body weight gain,
      and adiposity. The decrease in body weight and adiposity occurred relative to
      both ad libitum- and pair-fed controls, implying that reduced food intake in and
      of itself does not underlie all of these effects. Consistent with this, rats
      administered Ang II had increased whole body heat production and oxygen
      consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and
      beta(3)-adrenergic receptor expression in brown adipose tissue and beta3
      adrenergic receptor expression in white adipose tissue, which is suggestive of
      enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also
      increased hypothalamic agouti-related peptide and decreased hypothalamic
      proopiomelanocortin expression, consistent with a state of energy deficit.
      Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid
      releasing hormones within the hypothalamus. These results suggest that Ang II
      acts in the brain to promote negative energy balance and that contributing
      mechanisms include an alteration in the hypothalamic circuits regulating energy
      balance, a decrease in food intake, an increase in energy expenditure, and an
      increase in sympathetic activation of brown and white adipose tissue.

PMID- 21862726
TI  - Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both
      PPARalpha-dependent and -independent pathways.
AB  - Peroxisome proliferator-activated receptors (PPARs) control energy homeostasis.
      In this study, we showed that farnesol, a naturally occurring ligand of PPARs,
      could ameliorate metabolic diseases. Obese KK-Ay mice fed a high-fat diet (HFD)
      containing 0.5% farnesol showed significantly decreased serum glucose level,
      glucosuria incidence, and hepatic triglyceride contents. Farnesol-containing HFD
      upregulated the mRNA expressions of PPARalpha target genes involved in fatty acid
      oxidation in the liver. On the other hand, farnesol was not effective in
      upregulating the mRNA expressions of PPARgamma target genes in white adipose
      tissues. Experiments using PPARalpha-deficient [(-/-)] mice revealed that the
      upregulation of fatty acid oxidation-related genes required PPARalpha function,
      but the suppression of hepatic triglyceride accumulation was partially PPARalpha
      dependent. In hepatocytes isolated from the wild-type and PPARalpha (-/-) mice,
      farnesol suppressed triglyceride synthesis. In luciferase assay, farnesol
      activated both PPARalpha and the farnesoid X receptor (FXR) at similar
      concentrations. Moreover, farnesol increased the mRNA expression level of a small
      heterodimer partner known as one of the FXR target genes and decreased those of
      sterol regulatory element-binding protein-1c and fatty acid synthase in both the
      wild-type and PPARalpha (-/-) hepatocytes. These findings suggest that farnesol
      could improve metabolic abnormalities in mice via both PPARalpha-dependent and 
      independent pathways and that the activation of FXR by farnesol might contribute
      partially to the PPARalpha-independent hepatic triglyceride content-lowering
      effect. To our knowledge, this is the first study on the effect of the dual
      activators of PPARalpha and FXR on obesity-induced metabolic disorders.

PMID- 21862727
TI  - Alternative splice variant PGC-1alpha-b is strongly induced by exercise in human
      skeletal muscle.
AB  - The present study investigated whether exercise induces the expression of PGC
      1alpha splice variants in human skeletal muscle and the possible influence of
      metabolic perturbation on this response. The subjects exercised one leg for 45
      min with restricted blood flow (R-leg), followed by 45 min of exercise using the
      other leg at the same absolute workload but with normal blood flow (NR-leg). This
      ischemic model (R-leg) has been shown previously to induce a greater metabolic
      perturbation and enhance the expression of PGC-1alpha beyond that observed in the
      NR-leg. Cultured human myotubes were used to test suggested exercise-induced
      regulatory stimuli of PGC-1alpha. We showed, for the first time, that transcripts
      from both the canonical promoter (PGC-1alpha-a) and the proposed upstream-located
      promoter (PGC-1alpha-b) are present in human skeletal muscle. Both transcripts
      were upregulated after exercise in the R-leg, but the fold change increase of PGC
      1alpha-b was much greater than that of PGC-1alpha-a. No differences were observed
      between the two conditions regarding the marker for calcineurin activation,
      MCIP1, or p38 phosphorylation. AMPK phosphorylation increased to a greater extent
      in the R-leg, and AICAR stimulation of cultured human myotubes induced the
      expression of PGC-1alpha-a and PGC-1alpha-b. AICAR combined with norepinephrine
      yielded an additive effect on the PGC-1alpha-b expression only. Our results
      indicate clearly that exercise can activate an upstream promoter in humans and
      support AMPK as a major regulator of transcripts from the canonical PGC-1alpha
      promoter and the involvement of beta-adrenergic stimulation in combination with
      AMPK in the regulation of PGC-1alpha-b.

PMID- 21862728
TI  - Re: Hypertension as a biomarker of efficacy in patients with metastatic renal
      cell carcinoma treated with sunitinib.

PMID- 21862729
TI  - mRNA expression of BRCA1, PIAS1, and PIAS4 and survival after second-line
      docetaxel in advanced gastric cancer.
AB  - Breast cancer susceptibility gene 1 (BRCA1) has a central role in chemotherapy
      induced DNA damage response. The protein inhibitor of activated STAT (PIAS)
      family of proteins, PIAS1 and PIAS4, are also necessary for adequate DNA damage
      repair. To further understand the role of BRCA1 in DNA repair, we examined the
      mRNA expression of these genes in 133 advanced (stage III-IV) gastric cancer
      patients using quantitative reverse transcription polymerase chain reaction. All
      P values were two-sided. The median overall survival was 12.5 months (95%
      confidence interval [CI] = 9.8 to 13.4 months). Among 59 patients receiving
      second-line docetaxel, the median overall survival was 25.8 months (95% CI = 9.2
      to 42.4 months) for patients with high BRCA1 expression, 19.1 months (95% CI =
      3.4 to 34.8 months) for those with intermediate expression, and 9.5 months (95%
      CI = 8.7 to 10.2 months) for those with low expression (P = .0062). The risk of
      mortality was higher in patients with low BRCA1 levels compared with high BRCA1
      levels (hazard ratio of death = 2.49, 95% CI = 1.03 to 5.97, P = .037). Survival
      in patients receiving second-line docetaxel-based chemotherapy showed a similar
      trend with PIAS1 and PIAS4 mRNA expression levels, although the associations for
      PIAS4 were not statistically significant.

PMID- 21862730
TI  - Clinical breast examination: preliminary results from a cluster randomized
      controlled trial in India.
AB  - A cluster randomized controlled trial was initiated in the Trivandrum district
      (Kerala, India) on January 1, 2006, to evaluate whether three rounds of triennial
      clinical breast examination (CBE) can reduce the incidence rate of advanced
      disease incidence and breast cancer mortality. A total of 275 clusters that
      included 115,652 healthy women, aged 30-69 years, were randomly allocated to
      intervention (CBE; 133 clusters; 55,844 women) or control (no screening; 142
      clusters; 59,808 women) groups. Performance characteristics (sensitivity,
      specificity, false-positive rate, and positive predictive value) of CBE were
      evaluated. An intention-to-treat analysis was performed for comparison of
      incidence rates between the intervention and control groups. Preliminary results
      for incidence are based on follow-up until May 31, 2009, when the first round of
      screening was completed. Of the 50,366 women who underwent CBE, 30 breast cancers
      were detected among 2880 women with suspicious findings in CBE screening that
      warranted further investigations. Sensitivity, specificity, false-positive rate,
      and positive predictive value of CBE were 51.7% (95% confidence interval [CI] =
      38.2% to 65.0%), 94.3% (95% CI = 94.1% to 94.5%), 5.7% (95% CI = 5.5% to 5.9%),
      and 1.0% (95% CI = 0.7% to 1.5%), respectively. The age-standardized incidence
      rates for early-stage (stage IIA or lower) breast cancer were 18.8 and 8.1 per
      100,000 women and for advanced-stage (stage IIB or higher) breast cancer were
      19.6 and 21.7 per 100,000 women, in the intervention and control groups,
      respectively.

PMID- 21862731
TI  - Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography
      perfusion for imaging of reversible myocardial ischemia: comparison with magnetic
      resonance imaging.
AB  - BACKGROUND: Coronary computed tomography angiography (CTA) enables accurate
      anatomic evaluation of coronary artery stenosis but lacks information about
      hemodynamic significance. The aim of this study was to evaluate 128-slice
      myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch
      mode, in comparison with cardiac MRI (CMR). METHODS AND RESULTS: Thirty-nine
      patients with intermediate to high coronary risk profile underwent adenosine
      stress 128-slice dual source CTP (128*0.6 mm, 0.28 seconds). Among those, 30
      patients (64 +/- 10 years, 6% women) also underwent adenosine stress CMR (1.5T).
      The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch
      factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using
      either high-pitch (heart rate <63 bpm) or prospective ECG-triggering (heart rate
      >63 bpm). Results were compared with CMR and with invasive angiography in 25
      patients. The performance of stress-CTP for detection of myocardial perfusion
      defects compared with CMR was sensitivity, 96%; specificity, 88%; positive
      predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel);
      and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The
      accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was
      sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25
      patients who underwent invasive angiography, the accuracy of CTA for detection of
      stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%;
      and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to
      CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv.
      CONCLUSIONS: Adenosine-induced stress 128-slice dual-source high-pitch myocardial
      CTP allows for simultaneously assessment of reversible myocardial ischemia and
      coronary stenosis, with good diagnostic accuracy as compared with CMR and
      invasive angiography, at a very low radiation exposure.

PMID- 21862733
TI  - Atrial remodeling and the substrate for atrial fibrillation in rat hearts with
      elevated afterload.
AB  - BACKGROUND: Although arterial hypertension and left ventricular hypertrophy are
      considered good epidemiological indicators of the risk of atrial fibrillation
      (AF) in patients, the link between elevated afterload and AF remains unclear. We
      investigated atrial remodeling and the substrate for arrhythmia in a surgical
      model of elevated afterload in rats. METHODS AND RESULTS: Male Wistar rats (aged
      3-4 weeks) were anesthetized and subjected to either partial stenosis of the
      ascending aorta (AoB) or sham operation (Sham). Experiments were performed on
      excised hearts 8, 14, and 20 weeks after surgery. Unipolar electrograms were
      recorded from the left atrial epicardial surface of perfused hearts using a 5*5
      electrode array. Cryosections of left atrial tissue were retained for
      histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed
      marked left atrial hypertrophy and fibrosis at 14 and 20 weeks postsurgery. The
      incidence and duration of pacing-induced AF was increased in hearts from AoB rats
      at 20 weeks postsurgery. The substrate for arrhythmia was associated with reduced
      vectorial conduction velocity and greater inhomogeneity in conduction but without
      changes in effective refractory period. Left atrial expression of the gap
      junction protein, connexin43, was markedly reduced in AoB compared with Sham
      hearts. CONCLUSIONS: Using a small-animal model, we demonstrate that elevated
      afterload in the absence of systemic hypertension results in increased
      inducibility of AF and left atrial remodeling involving fibrosis, altered atrial
      connexin43 expression, and marked conduction abnormalities.

PMID- 21862732
TI  - Quality of care and outcomes in women hospitalized for heart failure.
AB  - BACKGROUND: Although women account for a significant proportion of heart failure
      (HF) hospitalizations, data on the quality of care and in-hospital outcomes in
      women are limited. METHODS AND RESULTS: We examined The Joint Commission
      performance measures, other quality metrics, length of stay, and in-hospital
      mortality in women using 99 841 HF admissions (January 2005 to June 2009) at 248
      hospitals participating in the American Heart Association Get With The Guidelines
      Heart Failure registry. Women accounted for 50% of the HF admissions and were
      older (mean age, 74+/-14 versus 69+/-14 years), more likely to have hypertension
      (77% versus 72%), and less likely to have coronary disease (44% versus 53%) or
      renal insufficiency (18% versus 23%) than men (all P<0.001). The presenting
      symptoms were similar to men, but women had higher admission systolic blood
      pressure (mean, 144+/-31 versus 137+/-30 mm Hg; P<0.001) and ejection fraction
      (mean, 0.44+/-0.17% versus 0.34+/-0.16%; P<0.001). After adjustment for baseline
      differences, eligible women were less likely than men to have measurement of left
      ventricular function (adjusted odds ratio [OR], 0.81; 95% CI, 0.76 to 0.86) and
      to receive anticoagulation for atrial fibrillation (adjusted OR, 0.91; 95% CI,
      0.86 to 0.96) or implantable cardioverter-defibrillators (adjusted OR, 0.70; 95%
      CI, 0.65 to 0.75) but were as likely to receive discharge instructions,
      angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta
      blockers, and smoking cessation counseling at discharge. Although the median
      length of stay was 4 days, women were more likely than men to be hospitalized >4
      days (adjusted OR, 1.13; 95% CI, 1.10 to 1.16) and >7 days (adjusted OR, 1.07;
      95% CI, 1.04 to 1.11). Women had comparable in-hospital mortality to men
      (adjusted OR, 1.05; 95% CI, 0.96 to 1.14). CONCLUSIONS: Compared to men, women
      hospitalized for HF differ in many clinical characteristics and length of stay
      but have similar clinical presentations, receive similar quality of care for most
      but not all measures, and experience similar in-hospital mortality.

PMID- 21862734
TI  - The cover. Ophelia ("And he will not come back again").

PMID- 21862735
TI  - A piece of my mind. The road warriors.

PMID- 21862736
TI  - As production goes global, drug supply faces greater risks to safety, quality.

PMID- 21862737
TI  - Longer pauses between CPR compressions and defibrillation may decrease survival.

PMID- 21862738
TI  - Meth use linked to risk of Parkinson disease.

PMID- 21862739
TI  - Readmission rates after total hip arthroplasty.

PMID- 21862740
TI  - Major birth defects after exposure to newer-generation antiepileptic drugs.

PMID- 21862741
TI  - Major birth defects after exposure to newer-generation antiepileptic drugs.

PMID- 21862742
TI  - Medical kits for in-flight medical emergencies.

PMID- 21862743
TI  - Body adiposity index, body mass index, and body fat in white and black adults.

PMID- 21862744
TI  - Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of
      intensity of dietary advice on serum lipids in hyperlipidemia: a randomized
      controlled trial.
AB  - CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary
      portfolio) has proven highly effective in lowering serum cholesterol under
      metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary
      portfolio administered at 2 levels of intensity on percentage change in low
      density lipoprotein cholesterol (LDL-C) among participants following self
      selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351
      participants with hyperlipidemia from 4 participating academic centers across
      Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June
      25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months.
      INTERVENTION: Participants received dietary advice for 6 months on either a low
      saturated fat therapeutic diet (control) or a dietary portfolio, for which
      counseling was delivered at different frequencies, that emphasized dietary
      incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine
      dietary portfolio involved 2 clinic visits over 6 months and intensive dietary
      portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES:
      Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat
      analysis of 345 participants, the overall attrition rate was not significantly
      different between treatments (18% for intensive dietary portfolio, 23% for
      routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The
      LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI],
      168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95%
      CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95%
      CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001)
      for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or 
      8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL
      C reductions for each dietary portfolio were significantly more than the control
      diet (P < .001, respectively). The 2 dietary portfolio interventions did not
      differ significantly (P = .66). Among participants randomized to one of the
      dietary portfolio interventions, percentage reduction in LDL-C on the dietary
      portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001).
      CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat
      dietary advice resulted in greater LDL-C lowering during 6 months of follow-up.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

PMID- 21862745
TI  - Association of ICU or hospital admission with unintentional discontinuation of
      medications for chronic diseases.
AB  - CONTEXT: Patients discharged from acute care hospitals may be at risk for
      unintentional discontinuation of medications prescribed for chronic diseases. The
      intensive care unit (ICU) may pose an even greater risk because of the focus on
      acute events and the presence of multiple transitions in care. OBJECTIVE: To
      evaluate rates of potentially unintentional discontinuation of medications
      following hospital or ICU admission. DESIGN, SETTING, AND PATIENTS: A population
      based cohort study using administrative records from 1997 to 2009 of all
      hospitalizations and outpatient prescriptions in Ontario, Canada; it included
      396,380 patients aged 66 years or older with continuous use of at least 1 of 5
      evidence-based medication groups prescribed for long-term use: (1) statins, (2)
      antiplatelet/anticoagulant agents, (3) levothyroxine, (4) respiratory inhalers,
      and (5) gastric acid-suppressing drugs. Rates of medication discontinuation were
      compared across 3 groups: patients admitted to the ICU, patients hospitalized
      without ICU admission, and nonhospitalized patients (controls). Odds ratios (ORs)
      were calculated and adjusted for patient demographics, clinical factors, and
      health services use. MAIN OUTCOME MEASURES: The primary outcome was failure to
      renew the prescription within 90 days after hospital discharge. RESULTS: Patients
      admitted to the hospital (n = 187,912) were more likely to experience potentially
      unintentional discontinuation of medications than controls (n = 208,468) across
      all medication groups examined. The adjusted ORs (AORs) ranged from 1.18 (95% CI,
      1.14-1.23) for discontinuing levothyroxine in 12.3% of hospitalized patients (n =
      6831) vs 11.0% of controls (n = 7114) to an AOR of 1.86 (95% CI, 1.77-1.97) for
      discontinuing antiplatelet/anticoagulant agents in 19.4% of hospitalized patients
      (n = 5564) vs 11.8% of controls (n = 2535). With ICU exposure, the AORs ranged
      from 1.48 (95% CI, 1.39-1.57) for discontinuing statins in 14.6% of ICU patients
      (n = 1484) to an AOR of 2.31 (95% CI, 2.07-2.57) for discontinuing
      antiplatelet/anticoagulant agents in 22.8% of ICU patients (n = 522) vs the
      control group. Admission to an ICU was associated with an additional risk of
      medication discontinuation in 4 of 5 medication groups vs hospitalizations
      without an ICU admission. One-year follow-up of patients who discontinued
      medications showed an elevated AOR for the secondary composite outcome of death,
      emergency department visit, or emergent hospitalization of 1.07 (95% CI, 1.03
      1.11) in the statins group and of 1.10 (95% CI, 1.03-1.16) in the
      antiplatelet/anticoagulant agents group. CONCLUSIONS: Patients prescribed
      medications for chronic diseases were at risk for potentially unintentional
      discontinuation after hospital admission. Admission to the ICU was generally
      associated with an even higher risk of medication discontinuation.

PMID- 21862746
TI  - Automated identification of postoperative complications within an electronic
      medical record using natural language processing.
AB  - CONTEXT: Currently most automated methods to identify patient safety occurrences
      rely on administrative data codes; however, free-text searches of electronic
      medical records could represent an additional surveillance approach. OBJECTIVE:
      To evaluate a natural language processing search-approach to identify
      postoperative surgical complications within a comprehensive electronic medical
      record. DESIGN, SETTING, AND PATIENTS: Cross-sectional study involving 2974
      patients undergoing inpatient surgical procedures at 6 Veterans Health
      Administration (VHA) medical centers from 1999 to 2006. MAIN OUTCOME MEASURES:
      Postoperative occurrences of acute renal failure requiring dialysis, deep vein
      thrombosis, pulmonary embolism, sepsis, pneumonia, or myocardial infarction
      identified through medical record review as part of the VA Surgical Quality
      Improvement Program. We determined the sensitivity and specificity of the natural
      language processing approach to identify these complications and compared its
      performance with patient safety indicators that use discharge coding information.
      RESULTS: The proportion of postoperative events for each sample was 2% (39 of
      1924) for acute renal failure requiring dialysis, 0.7% (18 of 2327) for pulmonary
      embolism, 1% (29 of 2327) for deep vein thrombosis, 7% (61 of 866) for sepsis,
      16% (222 of 1405) for pneumonia, and 2% (35 of 1822) for myocardial infarction.
      Natural language processing correctly identified 82% (95% confidence interval
      [CI], 67%-91%) of acute renal failure cases compared with 38% (95% CI, 25%-54%)
      for patient safety indicators. Similar results were obtained for venous
      thromboembolism (59%, 95% CI, 44%-72% vs 46%, 95% CI, 32%-60%), pneumonia (64%,
      95% CI, 58%-70% vs 5%, 95% CI, 3%-9%), sepsis (89%, 95% CI, 78%-94% vs 34%, 95%
      CI, 24%-47%), and postoperative myocardial infarction (91%, 95% CI, 78%-97%) vs
      89%, 95% CI, 74%-96%). Both natural language processing and patient safety
      indicators were highly specific for these diagnoses. CONCLUSION: Among patients
      undergoing inpatient surgical procedures at VA medical centers, natural language
      processing analysis of electronic medical records to identify postoperative
      complications had higher sensitivity and lower specificity compared with patient
      safety indicators based on discharge coding.

PMID- 21862747
TI  - Progression of left ventricular diastolic dysfunction and risk of heart failure.
AB  - CONTEXT: Heart failure incidence increases with advancing age, and approximately
      half of patients with heart failure have preserved left ventricular ejection
      fraction. Although diastolic dysfunction plays a role in heart failure with
      preserved ejection fraction, little is known about age-dependent longitudinal
      changes in diastolic function in community populations. OBJECTIVE: To measure
      changes in diastolic function over time and to determine the relationship between
      diastolic dysfunction and the risk of subsequent heart failure. DESIGN, SETTING,
      AND PARTICIPANTS: Population-based cohort of participants enrolled in the Olmsted
      County Heart Function Study. Randomly selected participants 45 years or older (N
      = 2042) underwent clinical evaluation, medical record abstraction, and
      echocardiography (examination 1 [1997-2000]). Diastolic left ventricular function
      was graded as normal, mild, moderate, or severe by validated Doppler techniques.
      After 4 years, participants were invited to return for examination 2 (2001-2004).
      The cohort of participants returning for examination 2 (n = 1402 of 1960
      surviving [72%]) then underwent follow-up for ascertainment of new-onset heart
      failure (2004-2010). MAIN OUTCOME MEASURES: Change in diastolic function grade
      and incident heart failure. RESULTS: During the 4 (SD, 0.3) years between
      examinations 1 and 2, diastolic dysfunction prevalence increased from 23.8% (95%
      confidence interval [CI], 21.2%-26.4%) to 39.2% (95% CI, 36.3%-42.2%) (P < .001).
      Diastolic function grade worsened in 23.4% (95% CI, 20.9%-26.0%) of participants,
      was unchanged in 67.8% (95% CI, 64.8%-70.6%), and improved in 8.8% (95% CI, 7.1%
      10.5%). Worsened diastolic dysfunction was associated with age 65 years or older
      (odds ratio, 2.85 [95% CI, 1.77-4.72]). During 6.3 (SD, 2.3) years of additional
      follow-up, heart failure occurred in 2.6% (95% CI, 1.4%-3.8%), 7.8% (95% CI, 5.8%
      13.0%), and 12.2% (95% CI, 8.5%-18.4%) of persons whose diastolic function
      normalized or remained normal, remained or progressed to mild dysfunction, or
      remained or progressed to moderate or severe dysfunction, respectively (P <
      .001). Diastolic dysfunction was associated with incident heart failure after
      adjustment for age, hypertension, diabetes, and coronary artery disease (hazard
      ratio, 1.81 [95% CI, 1.01-3.48]). CONCLUSIONS: In a population-based cohort
      undergoing 4 years of follow-up, prevalence of diastolic dysfunction increased.
      Diastolic dysfunction was associated with development of heart failure during 6
      years of subsequent follow-up.

PMID- 21862748
TI  - Association between biologic therapies for chronic plaque psoriasis and
      cardiovascular events: a meta-analysis of randomized controlled trials.
AB  - CONTEXT: Ustekinumab and briakinumab, monoclonal antibodies to the shared p40
      subunit of interleukin (IL)-12 and IL-23, have shown efficacy in treating chronic
      plaque psoriasis (CPP). Preliminary reports of major adverse cardiovascular
      events (MACEs) in psoriasis patients receiving anti-IL-12/23 agents have prompted
      concern. OBJECTIVE: To evaluate a possible association between biologic therapies
      for CPP and MACEs via meta-analysis. DATA SOURCES: Randomized controlled trials
      (RCTs) of anti-IL-12/23 (ustekinumab and briakinumab) agents and anti-tumor
      necrosis factor alpha (TNF-alpha) agents (adalimumab, etanercept, and infliximab)
      used in treating CPP were reviewed using the Cochrane Central Register of
      Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE from database inception
      to May 2011. The results of registered nonpublished completed studies were
      procured through abstract publications or poster presentations. STUDY SELECTION:
      Randomized, placebo-controlled, double-blind, monotherapy studies (with safety
      outcome data for MACE) of IL-12/23 antibodies and anti-TNF-alpha agents in
      adults. Studies of psoriatic arthritis were excluded. DATA EXTRACTION: Two
      investigators independently searched data while 6 investigators reviewed the
      abstracted data. RESULTS: A total of 22 RCTs comprising 10 183 patients met the
      predefined inclusion criteria. The primary outcome measure was MACE, a composite
      end point of myocardial infarction, cerebrovascular accident, or cardiovascular
      death during the placebo-controlled phase of treatment in patients receiving at
      least 1 dose of study agent or placebo. Absolute risk differences were used as an
      effect measure. There was no evidence of statistical heterogeneity across the
      studies using the I(2) statistic (I(2) = 0), allowing for combination of trial
      results using the Mantel-Haenszel fixed-effects method. During the placebo
      controlled phases of the anti-IL-12/23 studies, 10 of 3179 patients receiving
      anti-IL-12/23 therapies experienced MACEs compared with zero events in 1474
      patients receiving placebo (Mantel-Haenszel risk difference, 0.012 events/person
      year; 95% confidence interval [CI], -0.001 to 0.026; P =.12). In the anti-TNF
      alpha trials, only 1 of 3858 patients receiving anti-TNF-alpha agents experienced
      a MACE compared with 1 of 1812 patients receiving placebo (Mantel-Haenszel risk
      difference, -0.0005 events/person-year; 95% CI, -0.010 to 0.009; P = .94).
      CONCLUSIONS: Compared with placebo, there was no significant difference in the
      rate of MACEs observed in patients receiving anti-IL-12/IL-23 antibodies or anti
      TNF-alpha treatments. This study may have been underpowered to identify a
      significant difference.

PMID- 21862749
TI  - The older smoker.

PMID- 21862750
TI  - Going home on the right medications: prescription errors and transitions of care.

PMID- 21862751
TI  - The promise of electronic records: around the corner or down the road?

PMID- 21862752
TI  - JAMA patient page. Psoriasis.

PMID- 21862753
TI  - Can laypersons be trained to effectively deliver osteopathic manual therapy to
      patients with HIV?

PMID- 21862754
TI  - Safety and efficacy of immediate postoperative feeding and bowel stimulation to
      prevent ileus after major gynecologic surgical procedures.
AB  - CONTEXT: Postoperative ileus is a major complication of abdominal surgical
      procedures OBJECTIVE: To evaluate the incidence of ileus and gastrointestinal
      morbidity in patients who received immediate postoperative feeding and bowel
      stimulation after undergoing major gynecologic surgical procedures. METHODS:
      During a 5-year period, the authors tracked demographic, surgical outcome, and
      follow-up information for 707 patients who underwent major gynecologic
      operations. All patients received the same postoperative orders, including
      immediate feeding of a diet of choice and bowel stimulation with 30 mL of
      magnesium hydroxide (milk of magnesia) twice daily until bowel movements
      occurred. RESULTS: Of 707 patients, 6 (<1%) had postoperative ileus. No patients
      experienced postoperative bowel obstruction and 2 patients (0.3%) had
      postoperative intestinal leak. No serious adverse effects associated with bowel
      stimulation were reported. CONCLUSION: Immediate postoperative feeding and bowel
      stimulation is a safe and effective approach to preventing ileus in patients who
      undergo major gynecologic surgical procedures.

PMID- 21862755
TI  - Health-related Internet use among patients of osteopathic physicians.
AB  - CONTEXT: Using the Internet has transformed communication and improved access to
      health-related information for patients and physicians. OBJECTIVE: To determine
      why patients use the Internet for health-related information, where patients find
      answers to their questions, and whether patient use of the Internet impacts the
      patient-physician relationship. This study focused on patients of osteopathic
      physicians to confirm previously published data in a more specific population.
      METHODS: An anonymous 25-item survey was distributed to patients in a primary
      care setting. The survey elicited information regarding demographics, health
      related Internet use, and discussion of Web-based health information during the
      clinical visit. RESULTS: Two hundred eighty-five patient surveys were collected.
      Data based on sex, age, education level, and ethnicity were evaluated. Two
      hundred fifty of 280 patients (89%) reported that they use the Internet to find
      health-related information, and 134 of 250 patients (54%) indicated that they
      changed their health-related behaviors based on information they found. Seventy
      three of 133 patients (55%) who changed their behaviors reported these findings
      to their physicians. This finding differed by age and ethnicity. Patients aged 50
      to 64 years (22 responses, 73%) were the most likely group to report behavioral
      changes to their physicians (P=.048). No patients who identified themselves as of
      Asian/Pacific Islander descent indicated that they reported behavioral changes to
      their physician (P=.043). Two hundred forty-two of 261 patients (93%) reported
      that their personal physician is the most reliable source for health information.
      CONCLUSION: Most patients use the Internet to find health-related information,
      but many of them are not reporting potentially important health-related
      behavioral changes to their physicians. However, most patients still consider
      their physician as the most reliable source for health-related information.
      Physicians should ask patients about Internet use and counsel them about where to
      find reliable, accurate, high-quality health information.

PMID- 21862756
TI  - Multiple primary cancers including mesothelioma of the tunica vaginalis: case
      report and literature review with primary care focus.
AB  - The development of multiple primary malignancies in an individual is rare and
      unfortunate, and the care of such a patient presents specific challenges. We
      report the diagnosis and progression of 3 histologically different primary
      cancers in 1 patient over the course of 15 years. At age 50 years, the patient
      received a diagnosis of transitional cell carcinoma of the bladder; treatment was
      successful. When the patient was 64 years old, mesothelioma of the tunica
      vaginalis was diagnosed, and computed tomography performed for staging purposes
      revealed a lung lesion, which was later diagnosed as adenocarcinoma. Treatment
      for the adenocarcinoma was also successful, but the patient continues to have
      recurrence of mesothelioma. To our knowledge, the present report is the first
      description of a case of 3 primary cancers that includes a mesothelioma of the
      tunica vaginalis. Because mesothelioma of the tunica vaginalis is rare, we
      reviewed the literature on its prevalence, presentation, management, and
      prognosis.

PMID- 21862758
TI  - Coriander (Coriandrum sativum L.) essential oil: its antibacterial activity and
      mode of action evaluated by flow cytometry.
AB  - The aim of this work was to study the antibacterial effect of coriander
      (Coriandrum sativum) essential oil against Gram-positive and Gram-negative
      bacteria. Antibacterial susceptibility was evaluated using classical
      microbiological techniques concomitantly with the use of flow cytometry for the
      evaluation of cellular physiology. Our results showed that coriander oil has an
      effective antimicrobial activity against all bacteria tested. Also, coriander oil
      exhibited bactericidal activity against almost all bacteria tested, with the
      exception of Bacillus cereus and Enterococcus faecalis. Propidium iodide
      incorporation and concomitant loss of all other cellular functions such as efflux
      activity, respiratory activity and membrane potential seem to suggest that the
      primary mechanism of action of coriander oil is membrane damage, which leads to
      cell death. The results obtained herein further encourage the use of coriander
      oil in antibacterial formulations due to the fact that coriander oil effectively
      kills pathogenic bacteria related to foodborne diseases and hospital infections.

PMID- 21862761
TI  - Imaging of the complications of acute pancreatitis.

PMID- 21862759
TI  - Proteomic and metabolomic profiling of a trait anxiety mouse model implicate
      affected pathways.
AB  - Depression and anxiety disorders affect a great number of people worldwide.
      Whereas singular factors have been associated with the pathogenesis of
      psychiatric disorders, growing evidence emphasizes the significance of
      dysfunctional neural circuits and signaling pathways. Hence, a systems biology
      approach is required to get a better understanding of psychiatric phenotypes such
      as depression and anxiety. Furthermore, the availability of biomarkers for these
      disorders is critical for improved diagnosis and monitoring treatment response.
      In the present study, a mouse model presenting with robust high versus low
      anxiety phenotypes was subjected to thorough molecular biomarker and pathway
      discovery analyses. Reference animals were metabolically labeled with the stable
      (15)N isotope allowing an accurate comparison of protein expression levels
      between the high anxiety-related behavior versus low anxiety-related behavior
      mouse lines using quantitative mass spectrometry. Plasma metabolomic analyses
      identified a number of small molecule biomarkers characteristic for the anxiety
      phenotype with particular focus on myo-inositol and glutamate as well as the
      intermediates involved in the tricarboxylic acid cycle. In silico analyses
      suggested pathways and subnetworks as relevant for the anxiety phenotype. Our
      data demonstrate that the high anxiety-related behavior and low anxiety-related
      behavior mouse model is a valuable tool for anxiety disorder drug discovery
      efforts.

PMID- 21862760
TI  - Peptide identification by database search of mixture tandem mass spectra.
AB  - In high-throughput proteomics the development of computational methods and novel
      experimental strategies often rely on each other. In certain areas, mass
      spectrometry methods for data acquisition are ahead of computational methods to
      interpret the resulting tandem mass spectra. Particularly, although there are
      numerous situations in which a mixture tandem mass spectrum can contain fragment
      ions from two or more peptides, nearly all database search tools still make the
      assumption that each tandem mass spectrum comes from one peptide. Common examples
      include mixture spectra from co-eluting peptides in complex samples, spectra
      generated from data-independent acquisition methods, and spectra from peptides
      with complex post-translational modifications. We propose a new database search
      tool (MixDB) that is able to identify mixture tandem mass spectra from more than
      one peptide. We show that peptides can be reliably identified with up to 95%
      accuracy from mixture spectra while considering only a 0.01% of all possible
      peptide pairs (four orders of magnitude speedup). Comparison with current
      database search methods indicates that our approach has better or comparable
      sensitivity and precision at identifying single-peptide spectra while
      simultaneously being able to identify 38% more peptides from mixture spectra at
      significantly higher precision.

PMID- 21862762
TI  - Advancing in your career.

PMID- 21862763
TI  - Whole-body diffusion-weighted imaging: the added value to whole-body MRI at
      initial diagnosis of lymphoma.
AB  - OBJECTIVE: The objective of our study was to evaluate the diagnostic performance
      of conventional whole-body MRI without and with diffusion-weighted imaging (DWI)
      in the detection of known (18)F-FDG-avid lymphomas. The conventional whole-body
      MRI protocol consisted of a T2-weighted sequence and a T2-weighted spectral
      attenuated inversion recovery (SPAIR) sequence with frequency-selective fat
      suppression. The second protocol used the same sequences as the first protocol
      but also included DWI. SUBJECTS AND METHODS: Seventeen patients with
      pathologically confirmed, newly diagnosed, untreated lymphoma were recruited. T2
      weighted and T2-weighted SPAIR images were evaluated first, separate from the DW
      images, and then were evaluated with the DW images. We used (18)F-FDG PET/CT as
      the standard of reference. True-positive, false-positive, and false-negative
      values were evaluated on a per-lesion basis. Tumor staging based on T2-weighted
      and T2-weighted SPAIR imaging without DWI and then with DWI was compared using
      the Ann Arbor staging system. RESULTS: True-positive lesions were increased from
      89% to 97%, false-positive lesions were increased from 3% to 6%, and false
      negative lesions were decreased from 11% to 3% by the addition of DWI. Diagnostic
      sensitivity was significantly increased (p = 0.002) by adding DWI. Lesions
      detected on DWI but not on T2-weighted and T2-weighted SPAIR imaging were located
      in renal (n = 1), paraaortic (n = 6), and pelvic (n = 3) lymph nodes. On DWI, 47%
      of the lesions (n = 55) were more conspicuous than on T2-weighted and T2-weighted
      SPAIR imaging; most of these lesions (58%, n = 32) were from lymph nodes in the
      pelvic or abdominal regions and bone marrow. No difference was found between T2
      weighted and T2-weighted SPAIR imaging without DWI and T2-weighted and T2
      weighted SPAIR imaging with DWI in lymphoma staging, being consistent with PET/CT
      in 88% of the patients (n = 15). CONCLUSION: The addition of DWI to conventional
      whole-body MRI sequences enhanced lesion conspicuity and improved diagnostic
      accuracy for lymphomas. With technical optimization, whole-body MRI with DWI, as
      a nonionizing imaging modality, may potentially be useful as an alternative
      method to PET/CT in the management of malignant lymphoma.

PMID- 21862764
TI  - Extrapulmonary small cell carcinoma: a pictorial review.
AB  - OBJECTIVE: Extrapulmonary small cell carcinoma (EPSCC) is a rare, aggressive
      neoplasm arising from virtually any organ. Numerous oncologic studies have
      addressed prognostic indicators and survival rates in EPSCC, however relatively
      little has been published regarding the imaging features and metastatic patterns
      of these uncommon tumors. This article provides a pictorial review of EPSCC in
      multiple organs, emphasizing the imaging appearance at presentation and the
      radiologic patterns of recurrence/metastasis. CONCLUSION: Although the appearance
      of EPSCC is often nonspecific, the typical presentation is large aggressive
      tumors that, similar to small cell carcinoma in the lung, often respond well to
      local therapy but tend to recur relentlessly at distant sites.

PMID- 21862765
TI  - 64-MDCT in mass casualty incidents: volume image reading boosts radiological
      workflow.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of the use of 64
      MDCT and volume image reading on the radiologic workflow during a mass casualty
      incident simulation. MATERIALS AND METHODS: For this simulation, casualties were
      taken to our level I trauma center, and triage was done with whole-body 64-MDCT.
      The complete raw dataset of thin-section images was sent to a dedicated 3D
      workstation for further interpretation and simultaneous reformations. This new
      reading method is called volume image reading. Several time frames were
      documented to evaluate the workflow: examination time, time needed for image
      processing, and mean image transfer rates. The results were compared with those
      of a previous study using a 4-MDCT with axial images only and transfer of data to
      a PACS. RESULTS: The time for complete image processing (acquisition,
      reconstruction, and transfer) for 64-MDCT was 4.1 minutes (range, 3.9-4.3
      minutes) compared with 9.0 minutes (range, 6.4-10.2 minutes) for 4-MDCT (p <=
      0.001). The image processing capacity was 14.8 examinations/h for 64-MDCT
      compared with 6.7 examinations/h for 4-MDCT. The mean number of images was 953
      for 64-MDCT compared with 202 for 4-MDCT (p <= 0.001). There were no significant
      differences between 64- and 4-MDCT for the time needed to prepare patients.
      CONCLUSION: The use of 64-MDCT with volume image reading led to evident
      advantages in the radiologic trauma workflow compared with 4-MDCT. Reading of the
      full image set including reformations can be initiated earlier with volume image
      reading.

PMID- 21862766
TI  - MRI after arthroplasty: comparison of MAVRIC and conventional fast spin-echo
      techniques.
AB  - OBJECTIVE: The goal of this study was to evaluate the quality of images obtained
      with a prototype imaging technique, multiacquisition variable-resonance image
      combination (MAVRIC), compared with fast spin-echo (FSE) images in the evaluation
      of patients who have undergone hip, shoulder, or knee arthroplasty. MATERIALS AND
      METHODS: MRI with metal-artifact reduction FSE and MAVRIC sequences was performed
      in the care of 122 patients who had undergone 74 hip, 27 shoulder, and 21 knee
      arthroplasties. The FSE and MAVRIC images were subjectively graded for
      visualization of the synovium, prosthesis-bone interface, and hip abductors or
      supraspinatus tendon. The presence of synovitis, osteolysis, or supraspinatus
      tendon tear was recorded. RESULTS: Visualization of the synovium was
      significantly better on MAVRIC images than on FSE images of the hip (p < 0.0001),
      shoulder (p < 0.01), and knee (p < 0.01). Synovitis was detected only on the
      MAVRIC images of nine subjects (12%) who had undergone hip arthroplasty and five
      subjects (18%) who had undergone shoulder arthroplasty. Visualization of the
      periprosthetic bone was significantly better on MAVRIC images of the hip (p <
      0.0001), shoulder (p < 0.0001), and knee (p < 0.01). Osteolysis was detected only
      on the MAVRIC images of 12 subjects (16%) who had undergone hip arthroplasty, six
      (22%) who had undergone shoulder arthroplasty, and five (24%) who had undergone
      knee arthroplasty. Visualization of the supraspinatus tendon was significantly
      better on MAVRIC images (p < 0.0001). Supraspinatus tendon tears in 12 subjects
      (44%) were detected only on MAVRIC images. CONCLUSION: MAVRIC complements the
      information on FSE images after arthroplasty and is a useful additional sequence,
      particularly when there is concern about synovitis, periprosthetic osteolysis, or
      the presence of a supraspinatus tendon tear.

PMID- 21862767
TI  - Imaging characteristics of benign, malignant, and infectious jaw lesions: a
      pictorial review.
AB  - OBJECTIVE: The purpose of this article is to describe the indications and
      appropriate imaging studies for various jaw tumors and tumorlike lesions, the
      imaging findings, the differential diagnosis, and appropriate treatment options.
      CONCLUSION: It is important for radiologists to recognize the indications and
      appropriate imaging studies for various jaw lesions. Radiography is typically
      used for first-line imaging. If necessary, it is followed by CT for evaluation of
      osseous lesions and MRI for characterization of soft-tissue lesions.

PMID- 21862768
TI  - Assessing rheumatoid arthritis with ultrasound of the hands.
AB  - OBJECTIVE: The purpose of this video article is to show the sonographic
      techniques and findings in evaluating the joints of the hands in patients with
      possible inflammatory arthritis and to review the sonographic appearance and
      grading of synovitis. CONCLUSION: This video article shows the value of a
      targeted approach for musculoskeletal ultrasound of the hand and wrist in
      patients with rheumatoid arthritis. On completion of this video article, the
      participant should be able to develop an appropriate diagnostic and therapeutic
      approach using ultrasound for the treatment of patients with rheumatoid
      arthritis.

PMID- 21862769
TI  - New and improved orthopedic hardware for the 21st century: part 1, upper
      extremity.
AB  - OBJECTIVE: The purpose of this article is to provide a survey of new orthopedic
      products for use in the upper extremity. CONCLUSION: Knowledge of the physiologic
      purpose, orthopedic trends, imaging findings, and complications is important in
      assessing new orthopedic devices.

PMID- 21862770
TI  - New and improved orthopedic hardware for the 21st century: part 2, lower
      extremity and axial skeleton.
AB  - OBJECTIVE: The purpose of this article is to provide a survey of new orthopedic
      products for use in the lower extremity and axial skeleton. CONCLUSION: Knowledge
      of the physiologic purpose, orthopedic trends, imaging findings, and
      complications is important in assessing new orthopedic devices.

PMID- 21862771
TI  - Effects of iopamidol-370 versus iodixanol-320 on coronary contrast, branch
      depiction, and heart rate variability in dual-source coronary MDCT angiography.
AB  - OBJECTIVE: The purpose of this article is to assess whether iopamidol-370
      provides superior vascular contrast of the coronaries and depiction of anatomic
      detail without affecting heart rate and beat-to-beat variability during coronary
      dual-source MDCT compared with iodixanol-320. SUBJECTS AND METHODS: In this
      prospective trial, coronary CT angiography was performed on 60 adult patients
      using either iopamidol-370 or iodixanol-320. Cohorts were matched by age,
      habitus, sex, and baseline heart rate, with cohort sizes determined by power
      analysis. All studies were performed on a dual-source MDCT scanner with
      retrospective ECG-gating utilizing automatic pitch adjustment. Data assessment
      focused on heart rate variability during contrast administration statistically
      evaluated as Student t test comparisons within and between cohorts, coronary
      contrast-to-noise ratio analysis of the main coronary arteries utilizing Student
      t test comparisons between cohorts, and coronary branch depiction and
      distribution analysis in dual-reader consensus decisions between cohorts.
      RESULTS: Thirty patients matched for age, habitus, sex, and heart rate were
      evaluated in each cohort. ECG analyses found a statistically significant (p =
      0.013) decrease in heart rate during administration of iodixanol-320. Beat-to
      beat variations, expressed as coefficient of variation, within and among cohorts
      were low (coefficient of variation, < 0.05). Contrast-to-noise ratio was
      significantly increased for iopamidol-370 versus iodixanol-320 (aortic root, p =
      0.021; left main, p = 0.032; left anterior descending, p = 0.033; left
      circumflex, p = 0.039; and right, p = 0.009). Analysis of coronary branch
      visualization revealed improved depiction for iopamidol-370 compared with
      iodixanol-320. CONCLUSION: Iopamidol-370, with its higher iodine concentration,
      provided greater vascular contrast of the arterial coronary tree and improved
      depiction of anatomic detail without significantly impacting cardiac heart rate
      during coronary MDCT imaging, as compared with iodixanol-320.

PMID- 21862772
TI  - Thoracic manifestations of inflammatory bowel disease.
AB  - OBJECTIVE: The purpose of this article is to present the spectrum of inflammatory
      bowel disease manifestations in the chest, including the airways, lung
      parenchyma, pulmonary vasculature, and serosal surfaces. CONCLUSION: The spectrum
      of inflammatory bowel disease manifestations in the chest is broad, and the
      manifestations may mimic other diseases. Knowledge of these manifestations in
      conjunction with pertinent clinical data is essential for establishing the
      correct diagnosis and treatment.

PMID- 21862773
TI  - "MR-conditional" pacemakers: the radiologist's role in multidisciplinary
      management.
AB  - OBJECTIVE: The recent approval of an "MR-conditional" pacemaker system by the
      U.S. Food and Drug Administration allows patients with that pacemaker system to
      undergo MRI examinations within specific conditions. These examinations must be
      attended by radiology health care professionals with training for the use of the
      pacemaker system. CONCLUSION: Radiologists should be knowledgeable of the
      specific limitations with regard to patient isocenter and coil positioning within
      the required 1.5-T MR system and the importance that the pacer be programmed
      before and after scanning.

PMID- 21862774
TI  - Radiology of chest wall masses.
AB  - OBJECTIVE: The purpose of this article is to highlight the role of radiography,
      CT, PET/CT, and MRI in the diagnosis and management of chest wall lesions. Chest
      wall masses are caused by a spectrum of clinical entities. The lesions
      highlighted in this selection of case scenarios include neoplastic, inflammatory,
      and vascular lesions. CONCLUSION: Imaging evaluation with radiography, CT, MRI,
      and PET/CT plays an important role in the accurate diagnosis of chest wall
      lesions. It can also facilitate percutaneous biopsy, when it is indicated.
      Imaging enables accurate staging and is a key component of treatment planning for
      chest wall masses.

PMID- 21862775
TI  - Comprehensive MDCT evaluation of patients with pulmonary hypertension: diagnosing
      underlying causes with the updated Dana Point 2008 classification.
AB  - OBJECTIVE: Pulmonary hypertension is a challenge for imagers and clinicians, with
      a variety of possible underlying causes, each with its own specific treatment.
      Although the diagnosis is based on physiologic measurements, ECG-gated MDCT can
      play a vital role in elucidating underlying cardiac, vascular, and pulmonary
      causes. CONCLUSION: A revised system for pulmonary hypertension, the Dana Point
      classification, can provide a template for review of the myriad causes of this
      complex condition.

PMID- 21862776
TI  - Small serotonin-producing neuroendocrine tumor of the pancreas associated with
      pancreatic duct obstruction.
AB  - OBJECTIVE: Pancreatic neuroendocrine tumors expressing serotonin (carcinoid
      tumors) account for a small portion of pancreatic neuroendocrine tumors. The
      purpose of this study was to describe cases of small serotonin-producing
      pancreatic neuroendocrine tumors associated with pancreatic duct obstruction.
      CONCLUSION: Serotonin produced by pancreatic neuroendocrine tumors can induce
      fibrosis and pancreatic duct obstruction. Pancreatic neuroendocrine tumors should
      be considered when CT shows a small hypervascular mass associated with upstream
      pancreatic duct dilatation or atrophy. Evidence of small pancreatic
      neuroendocrine tumors should be sought in cases of idiopathic pancreatic duct
      stenosis.

PMID- 21862777
TI  - Assessment of renal lesions with blood oxygenation level-dependent MRI at 3 T:
      preliminary experience.
AB  - OBJECTIVE: The purpose of this article is to prospectively determine the
      feasibility of using blood oxygenation level-dependent (BOLD) MRI at 3 T in
      differentiating various renal lesions. SUBJECTS AND METHODS: Seventy-one patients
      (mean age, 53.8 years; range, 22-80 years) underwent kidney MRI, including BOLD
      MRI at 3 T. BOLD MRI was performed using a multiple fast-field echo (FFE)
      sequence to acquire 20 T2(*)-weighted images within a single breath-hold. The
      rate of spin dephasing (R2(*)) values of solid and benign cystic renal lesions
      were compared, and the results of four subgroups--simple cysts, renal cell
      carcinomas (RCCs), hemorrhagic cysts, and angiomyolipomas (AMLs)--were analyzed.
      The degree of overall imaging quality in BOLD MRI was also assessed. RESULTS: One
      hundred three renal lesions were detected in the 71 patients. The mean (+/- SD)
      R2(*) values of 45 solid lesions (30.6 +/- 19.4 1/s) were significantly higher
      than those of 58 benign cystic lesions (4.5 +/- 4.8 1/s; p < 0.001). The mean
      R2(*) values of simple cysts, RCCs, hemorrhagic cysts, and AMLs were 1.7 +/- 1.7,
      22.6 +/- 12.6, 10.7 +/- 3.7, and 48.0 +/- 25.5 1/s, respectively (p < 0.001). The
      degree of overall imaging quality in all patients was satisfactory or better.
      CONCLUSION: Renal BOLD MRI at 3 T is a feasible technique and may be useful for
      differentiating various renal lesions.

PMID- 21862778
TI  - Multivariate compensation of quantitative pulmonary emphysema metric variation
      from low-dose, whole-lung CT scans.
AB  - OBJECTIVE: Emphysema is a disease of the lung characterized by the destruction of
      the alveolar sac walls. Several quantitative densitometric measures of emphysema
      from wholelung CT have been proposed for evaluating disease severity and
      progression. However, a concern with these quantitative measures has been the
      large interscan variability observed during longitudinal studies of emphysema. To
      account for and reduce inherent measure variability, this work implements and
      evaluates the use of a multivariate random-effects model for correcting
      longitudinal variation in densitometric scores of emphysema due to inspiration.
      MATERIALS AND METHODS: The method of multivariate compensation was validated on
      three of the most commonly reported densitometric measures of emphysema: the
      emphysema index, histogram percentile, and fractal dimension. Two short-interval,
      zero-change datasets, one for model development (n = 105) and one for validation
      (n = 106), were retrospectively identified and used to ensure that all variation
      was caused by inherent measure variability. RESULTS: A statistically significant
      (F test, p < 0.001) reduction of 42.40% in measurement limits of agreement could
      be obtained after model application, with compensated emphysema metric
      differences showing 31-33% of the variance compared with uncompensated metric
      variance. CONCLUSION: Compensation was still effective when the trained model was
      applied to the second validation dataset. Multivariate compensation was found to
      be useful in reducing interscan measurement variability and should be applied to
      future longitudinal studies of emphysema.

PMID- 21862779
TI  - Cerebral venous thrombosis: a potential mimic of primary traumatic brain injury
      in infants.
AB  - OBJECTIVE: Hyperdense venous thrombi on unenhanced head CT may be misinterpreted
      as different types of extraaxial hemorrhages, and hemorrhagic venous infarctions
      may be interpreted as parenchymal contusion, leading to an incorrect diagnosis of
      trauma as the cause of the blood products. The purpose of this article is to show
      the various appearances of cerebral venous thrombosis (CVT) that mimic different
      types of hemorrhages and to show hemorrhagic venous infarctions that mimic
      parenchymal contusions. CONCLUSION: CVT, as an entity, must be kept in the
      differential diagnosis when patients present with extraaxial hyperdensities on
      unenhanced head CT so appropriate management can be initiated to minimize
      potentially devastating consequences.

PMID- 21862780
TI  - Reducing the dose of contrast medium in angiography by use of a highly sensitive
      receiver and synchrotron radiation system.
AB  - OBJECTIVE: Contrast medium causes side effects such as contrast-induced
      nephropathy, and the dose of contrast medium is a risk factor in their
      occurrence. To reduce doses of contrast medium, we developed an angiographic
      system with high definition and high sensitivity and reviewed its effectiveness.
      The system entails synchrotron radiation, which is characterized by high photon
      density and straightness of beam that together result in high resolution, and a
      high-gain avalanche rushing amorphous photoconductor receiver, which is 100 times
      more sensitive than conventional charge-coupled device cameras. MATERIALS AND
      METHODS: Diluted contrast medium was administered, and angiography of rat
      hindlimbs was performed with synchrotron radiation and the high-gain
      photoconductor receiver. The difference in gray-scale value between the
      background and contrast medium was calculated. Images were evaluated by counting
      of arteries. RESULTS: The difference in contrast at low levels was detected with
      the high-gain photoconductor receiver but not with the charge-coupled device
      camera. The photon density of synchrotron radiation with the high-gain
      photoconductor receiver was one-fifth that with the charge-coupled device camera.
      The high-gain photoconductor receiver had approximately 5 times the sensitivity
      of the charge-coupled device camera. CONCLUSION: Use of the synchrotron radiation
      and high-gain photoconductor receiver makes it possible to perform angiography
      with an extremely low concentration of contrast medium.

PMID- 21862781
TI  - Catheter-free survival after primary percutaneous stenting of malignant bile duct
      obstruction.
AB  - OBJECTIVE: The purpose of this article is to review the outcomes of patients with
      malignant biliary obstruction treated by immediate placement of a metallic stent
      at the time of percutaneous biliary drainage. MATERIALS AND METHODS: By a search
      of our PACS, we retrospectively identified all patients who underwent biliary
      stent placement at our interventional radiology section between January 2003 and
      December 2008. Of 564 biliary stent procedures, 71 primary percutaneous stents
      were placed at the time of biliary drainage; the other 493 were secondary
      percutaneous stents, placed at various durations after biliary drainage. Medical
      records and procedure reports were reviewed for the primary percutaneous stent
      group recording time to removal of the percutaneous catheter, periprocedural
      complications, subsequent biliary interventions, overall survival, and catheter
      free survival. RESULTS: After placement of primary percutaneous stents, 97% of
      patients were able to have their transhepatic catheter removed, and in 73% of
      patients, this 5-French catheter was removed within 24 hours. Major complications
      after placement of primary percutaneous stents included bile peritonitis
      requiring IV analgesia for less than 48 hours (5.6%) and fever with leukocytosis
      treated with IV antibiotics (8.5%) for 48-72 hours. Median overall survival was
      165 days, and 90% of patients had 100% catheter-free survival. Overall, 94% of
      survival days were catheter free. CONCLUSION: Placement of primary percutaneous
      stents when clinically appropriate has the advantage of avoiding an externalized
      drainage catheter and its attendant lifestyle limitations and complications. Most
      patients with malignant biliary obstruction, for whom expected survival is short,
      will experience 100% catheter-free survival after placement of a primary
      percutaneous stent.

PMID- 21862782
TI  - Common and rare collateral pathways in aortoiliac occlusive disease: a pictorial
      essay.
AB  - OBJECTIVE: The development of collateral pathways for arterial blood flow is
      common in the presence of atherosclerotic occlusive disease of the abdominal
      aorta and iliac arteries. The collateral pathways are divided into systemic
      systemic and systemic-visceral pathways. MDCT is commonly used to evaluate aortic
      stenosis and the resulting collateral pathways. CONCLUSION: Common and rare
      arterial collateral pathways are reviewed by 3D volume-rendered CT images.
      Visceral and lower extremity arterial embryology is reviewed.

PMID- 21862783
TI  - Imaging-guided preoperative hookwire localization of nonpalpable extramammary
      lesions.
AB  - OBJECTIVE: Imaging-guided hookwire localization of nonpalpable lesions in the
      breast is frequently performed preoperatively. Outside the breast, this procedure
      is useful for planning resection of lesions in anatomic regions without intrinsic
      landmarks. The purpose of this study was to review an experience with hookwire
      localization of nonpalpable extramammary lesions. CONCLUSION: Preoperative
      imaging-guided hookwire localization is a useful technique that allows precise
      exploration and resection of nonpalpable lesions and increases confidence that
      the lesions have been entirely resected.

PMID- 21862784
TI  - Imaging of hepatobiliary disorders complicating pregnancy.
AB  - OBJECTIVE: A variety of uncommon, but potentially devastating, hepatobiliary
      disorders may complicate pregnancy. Because of their rarity, such disorders may
      elude diagnosis and treatment may be delayed. Although some of these disorders
      can be diagnosed clinically, imaging plays an important role in the diagnosis of
      several pregnancy-related hepatobiliary disorders. CONCLUSION: The radiologist
      should be familiar with the imaging findings of hepatobiliary diseases that
      complicate pregnancy and can result in significant maternofetal morbidity and
      mortality.

PMID- 21862785
TI  - Managing contrast reactions after working hours.

PMID- 21862786
TI  - Interpreting radiologic studies obtained months earlier.

PMID- 21862787
TI  - Myotendinous foggy sign: subacute muscle denervation on MRI.

PMID- 21862788
TI  - Digitus ambiguus.

PMID- 21862789
TI  - Radiocarpal joint injection technique.

PMID- 21862790
TI  - Triangulation of breast lesions.

PMID- 21862791
TI  - Blended learning in medicine: trouble in paradise?

PMID- 21862792
TI  - Quantitative assessment of normal soft-tissue elasticity using shear-wave
      ultrasound elastography.
AB  - OBJECTIVE: The aim of this study was to measure the elasticity of various tissues
      and report it in kilopascals. SUBJECTS AND METHODS: The thyroid, submandibular,
      and parotid glands, masseter and gastrocnemius muscles, supraspinatus and
      Achilles tendons, renal cortex and pelvis, pancreas, and spleen of 127 healthy
      volunteers (89 women, 38 men; mean age, 37.72 +/- 9.11 years; range, 17-63 years)
      were evaluated with shear-wave ultrasound elastography. RESULTS: The mean
      elasticity values were determined to be 10.97 +/- 3.1 kPa for the thyroid, 10.92
      +/- 3.1 kPa for the submandibular glands, 10.38 +/- 3.5 kPa for the parotid
      glands, 10.4 +/- 3.7 kPa for the masseter muscle, 11.1 +/- 4.1 kPa for the
      gastrocnemius muscle, 31.2 +/- 13 kPa for the supraspinatus muscle, 51.5 +/- 25.1
      kPa for the Achilles tendons, 5.0 +/- 2.9 kPa for the renal cortex, 23.6 +/- 5.4
      kPa for the renal pelvis, 4.8 +/- 3 kPa for the pancreas, and 2.9 +/- 1.8 kPa for
      the spleen. CONCLUSION: Elasticity values were determined for different tissues
      with shear-wave ultrasound elastography. Further studies comparing the elasticity
      values of normal and pathologic tissues are necessary to determine the diagnostic
      role of this technique.

PMID- 21862793
TI  - Current status and update.

PMID- 21862794
TI  - Rheumatoid arthritis: ultrasound versus MRI.
AB  - OBJECTIVE: Rheumatoid arthritis is a predominantly joint-based disease affecting
      approximately 1% of the world's population. This article will address the
      increasing use of both ultrasound and MRI in the diagnosis and monitoring of
      rheumatoid arthritis and will highlight both the strengths and weaknesses of
      these two imaging modalities, with particular reference to bone erosions and
      synovitis. CONCLUSION: Because they can detect early disease, both ultrasound and
      MRI will become increasingly important in the diagnosis and management of
      rheumatoid arthritis. Future studies with increased patient numbers will be
      necessary if one of these two modalities is to emerge as a clear winner as the
      imaging modality of choice.

PMID- 21862795
TI  - Metal-induced artifacts in MRI.
AB  - OBJECTIVE: The purpose of this article is to review some of the basic principles
      of imaging and how metal-induced susceptibility artifacts originate in MR images.
      We will describe common ways to reduce or modify artifacts using readily
      available imaging techniques, and we will discuss some advanced methods to
      correct readout-direction and slice-direction artifacts. CONCLUSION: The presence
      of metallic implants in MRI can cause substantial image artifacts, including
      signal loss, failure of fat suppression, geometric distortion, and bright pile-up
      artifacts. These cause large resonant frequency changes and failure of many MRI
      mechanisms. Careful parameter and pulse sequence selections can avoid or reduce
      artifacts, although more advanced imaging methods offer further imaging
      improvements.

PMID- 21862796
TI  - Imaging of metal-on-metal hip prostheses.

PMID- 21862797
TI  - How to image metal-on-metal prostheses and their complications.
AB  - OBJECTIVE: Metal-on-metal arthroplasty is a durable alternative to traditional
      metal-on-polyethylene total hip replacement for young active patients. Although
      midterm results for resurfacing arthroplasty are reasonable, there is increasing
      recognition of the problem of metal-induced periprosthetic reactive masses.
      CONCLUSION: Imaging plays an important role in the investigation of symptomatic
      metal-on-metal arthroplasty. Radiographs will identify fracture and loosening,
      but cross-sectional imaging is required to diagnose and stage periprosthetic
      reactive masses.

PMID- 21862798
TI  - A biomechanical approach to MRI of acute knee injuries.
AB  - OBJECTIVE: MRI is routinely performed to evaluate acute complex knee injuries.
      This article will review the fundamental biomechanical forces underlying the most
      important and common injuries and correlate MRI findings with specific traumatic
      mechanisms. CONCLUSION: MRI findings can reveal the traumatic mechanisms in many
      acute knee injuries. By applying a biomechanical approach in MRI interpretation,
      it is possible to use easily detected lesions, such as osseous contusion and
      ligament rupture, to predict subtle but important abnormalities that might
      otherwise be missed. This systematic focused analysis enables a more accurate and
      rapid interpretation of knee MR studies.

PMID- 21862799
TI  - Hindfoot alignment measurements: rotation-stability of measurement techniques on
      hindfoot alignment view and long axial view radiographs.
AB  - OBJECTIVE: The purpose of this article is to identify the most rotation-stable
      hindfoot alignment measurement techniques on hindfoot alignment view and long
      axial view radiographs. MATERIALS AND METHODS: Hindfoot alignment was quantified
      on hindfoot alignment view and long axial view radiographs of a phantom in
      different rotation positions. Rotation stability of measurements using the
      calcaneal axis, the medial and lateral calcaneal contour, and the apparent moment
      arm were graphically compared. Interreader agreement was quantified using
      intraclass correlation coefficient. RESULTS: On hindfoot alignment view
      radiographs, measurements using the medial and lateral calcaneal contour were
      rotation stable (+/- 5 degrees ). Measurements using the calcaneal axis were not
      reliable and showed considerable divergence with phantom rotation. Measurements
      using the apparent moment arm manifested an almost linear relationship to phantom
      rotation. On long axial view radiographs, all measurements manifested an almost
      linear relationship to phantom rotation, whereas those using the calcaneal axis
      were the most rotation stable. Interreader agreement of all measurement
      techniques was perfect on both hindfoot alignment and long axial view radiographs
      (intraclass correlation coefficient, 0.8-0.98; p < 0.001). Interreader agreement
      was slightly better on long axial view radiographs. CONCLUSION: Hindfoot
      alignment measurements should be performed on hindfoot alignment view radiographs
      using the medial or lateral calcaneal contour or on long axial view radiographs
      using the calcaneal axis. Interreader agreement of hindfoot alignment
      measurements is slightly better on long axial view radiographs than on hindfoot
      alignment view radiographs.

PMID- 21862800
TI  - MR neurography: past, present, and future.
AB  - OBJECTIVE: MR neurography (MRN) has increasingly been used in clinical practice
      for the evaluation of peripheral nerve disease. This article reviews the historic
      perspective of MRN, the current imaging trends of this modality, and the future
      directions and applications that have shown potential for improved imaging and
      diagnostic capabilities. CONCLUSION: MRN has come a long way in the past 2
      decades. Excellent depiction of 3D nerve anatomy and pathology is currently
      possible. Further technical developments in diffusion-based nerve and muscle
      imaging, whole-body MRN, and nerve-specific MR contrast agents will likely play a
      major role in advancing this novel field and understanding peripheral
      neuromuscular diseases in the years to come.

PMID- 21862801
TI  - Superior labral anteroposterior lesions of the shoulder: part 1, anatomy and
      anatomic variants.
AB  - OBJECTIVE: The objectives of this article are to provide a pictorial review of
      labral anatomy and physiology, with particular attention to commonly seen
      anatomic variants and pitfalls, and to present standard imaging techniques and
      approaches to MRI interpretation to facilitate diagnosis and treatment of
      superior labral anteroposterior (SLAP) lesions. CONCLUSION: Imaging plays an
      important role in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy,
      related structures and variants, proper imaging techniques, and a systematic
      approach to MRI interpretation is important in the diagnosis and treatment
      planning of the 10 types of SLAP lesions. Arthroscopy offers a means for
      definitive diagnosis.

PMID- 21862802
TI  - Superior labral anteroposterior lesions of the shoulder: part 2, mechanisms and
      classification.
AB  - OBJECTIVE: The objectives of this article are to discuss the 10 distinct patterns
      of superior labral anteroposterior (SLAP) tears to facilitate adequate diagnosis
      and treatment. Correlations with clinical presentation, mechanism of injury, and
      treatment will enhance understanding. CONCLUSION: Imaging plays an important role
      in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy, related
      structures and variants, proper imaging techniques, and a systematic approach to
      MRI interpretation is important in the diagnosis and treatment planning of the 10
      types of SLAP lesions. Arthroscopy offers a means for definitive diagnosis.

PMID- 21862803
TI  - Assessment of mitral valve stenosis by helical MDCT: comparison with
      transthoracic doppler echocardiography and cardiac catheterization.
AB  - OBJECTIVE: We evaluated the precision of helical MDCT for the quantification of
      mitral valve stenosis (MVS) compared with transthoracic echocardiography (TTE)
      and cardiac catheterization. MATERIALS AND METHODS: A total of 28 patients with
      MVS of differing severity underwent an ECG-gated contrast-enhanced MDCT scan. The
      mitral valve area (MVA) was determined planimetrically by MDCT and was compared
      with Doppler TTE using the pressure half-time method and with cardiac
      catheterization using the Gorlin formula. RESULTS: Planimetry of the MVA with
      MDCT was feasible in all cases. The MVA on MDCT (1.88 +/- 0.76 cm(2)) was
      significantly larger than that seen with TTE (1.74 +/- 0.75 cm(2); p = 0.039) or
      cardiac catheterization (1.72 +/- 0.67 cm(2); p = 0.037). The correlation between
      MDCT and TTE (r = 0.90; p < 0.001; limits of agreement, +/- 0.65 cm(2)) and that
      between MDCT and cardiac catheterization (r = 0.86; p < 0.001; limits of
      agreement, +/- 0.76 cm(2)) were good and similar to the correlation between TTE
      and cardiac catheterization (r = 0.88; p < 0.001; limits of agreement, +/- 0.71
      cm(2)). The best cutoff level for detecting moderate-to-severe stenosis at MDCT
      was an MVA of 1.70 cm(2), resulting in a sensitivity, specificity, accuracy,
      positive predictive value, and negative predictive value of 73%, 88%, 82%, 80%,
      and 83%, respectively, with two false-positive and three false-negative results.
      CONCLUSION: The MVA planimetrically determined by MDCT is systematically larger
      than those calculated by Doppler TTE and cardiac catheterization. However,
      because of a good correlation between methods and adjustment for the systematic
      bias, MDCT may allow reliable quantification of MVS and effectual discrimination
      among severity grades, although discrepancies between methods remain in
      individual cases.

PMID- 21862804
TI  - CT screening and follow-up of lung nodules: effects of tube current-time setting
      and nodule size and density on detectability and of tube current-time setting on
      apparent size.
AB  - OBJECTIVE: The purpose of the study was to quantify and compare the effect of CT
      dose and of size and density of nodules on the detectability of lung nodules and
      to quantify the influence of CT dose on the size of the nodules. MATERIALS AND
      METHODS: From 50 patients a total of 125 cuboidal regions of interest (3 * 3 *
      1.5 cm volumes) showing a single nodule (<= 8 mm) and 27 normal cuboids were
      selected. Image sets were reconstructed with the software from raw data
      simulating different dose levels: 300 (original dose), 220, 180, 140, 100, 80,
      60, 50, 40, 30, 20, 10, and 5 reference mAs. A logistic regression model was used
      to analyze detectability for three blinded readers. Odds ratios were calculated
      for nodule size smaller than 3 mm versus 3 mm and larger and for nodule
      attenuation of -300 HU and greater versus less than -300 HU. RESULTS: Tube
      current-time settings of 10 mAs and greater were not associated with a
      significant difference in individual reader sensitivity compared with the
      standard setting of 300 mAs. At 5 mAs only one reader had a significant decrease
      in sensitivity, from 82% to 77% (p = 0.0035). According to the odds ratios and
      logistic regression results, the strongest negative effect on sensitivity can be
      assumed for low nodule density followed by small nodule size and dose level. The
      mean nodule volume measurement error between 5 and 300 mAs was 2.2% +/- 18% (SD)
      and much lower than the interobserver volume measurement error rate of 38% +/-
      45%. CONCLUSION: The results show the feasibility of a low-dose CT protocol at 10
      mAs for follow-up of lung nodules. Computer-aided volume measurement in follow-up
      of lung nodules decreases interobserver variability.

PMID- 21862805
TI  - Reference normal absolute and indexed values from ECG-gated MDCT: left atrial
      volume, function, and diameter.
AB  - OBJECTIVE: The purpose of this study was to retrospectively determine CT-based
      normal reference values of left atrial volume, function, and diameter normalized
      by age, sex, and body surface area. MATERIALS AND METHODS: The study group
      consisted of 74 subjects with normal findings at ECG-gated coronary CT
      angiography performed with retrospective gating. Analysis of left atrial volume
      (end-diastolic, end-systolic, and stroke volume) and function (ejection fraction)
      was performed with the Simpson method. Left atrial diameter was measured in the
      anteroposterior dimension. General linear model analysis was performed to model
      the data and assess statistical significance by age group after adjustment for
      sex and body surface area. RESULTS: The reference range for left atrial volume,
      function, and diameter was normalized (indexed) to age, sex, and body surface
      area in healthy subjects. A statistically significant difference was noted
      between left atrial volume and age without adjustment for sex and body surface
      area, but no statistically significant difference was found after adjustment for
      these variables. Sex and body surface area had a significant influence on left
      atrial volume, function, and diameter. CONCLUSION: Left atrial volume, function,
      and diameter normalized to age, sex, and body surface area can be reported from
      CTA datasets and may provide information important for patient care.

PMID- 21862806
TI  - Detection and grading of esophageal varices on liver CT: comparison of standard
      and thin-section multiplanar reconstructions in diagnostic accuracy.
AB  - OBJECTIVE: The objective of our study was to evaluate the performance of liver CT
      in the diagnosis of esophageal varices in patients with cirrhosis and to
      determine whether thin-section multiplanar reconstructions (MPRs) improve
      accuracy. MATERIALS AND METHODS: We identified 109 patients with cirrhosis who
      underwent endoscopy within 10 weeks after dual-phase liver MDCT supplemented with
      thin-section axial and coronal portal venous phase reconstructions. Two blinded
      radiologists independently evaluated each CT examination for the presence and
      sizes of varices using standard 5-mm axial versus 1- to 3-mm multiplanar images
      in separate sessions. Sensitivity, specificity, and predictive value calculations
      and receiver operating characteristic analysis were performed using endoscopy as
      the reference standard. Interobserver variability and correlation of CT size to
      variceal grade were assessed. RESULTS: Twenty-six cases of high-risk esophageal
      varices were identified; all except two were detected on CT by one of the readers
      on standard 5-mm images. For both readers, sensitivity and negative predictive
      value (NPV) for the discrimination of high-risk varices using a criterion of 2 mm
      or greater were nearly the same for the standard 5-mm images versus the 1- to 3
      mm multiplanar images (sensitivity and NPV: reader 1, 96% and 98% vs 96% and 99%;
      reader 2, and 89% and 95% vs 89% and 96%, respectively). Standard 5-mm images
      yielded a lower specificity for high-risk esophageal varices than the thin
      section multiplanar images, and this difference was statistically significant for
      reader 2. Substantial interobserver agreement was noted for both esophageal
      varices detection and size measurements. CONCLUSION: Standard liver CT is
      sensitive for the detection of high-risk varices and deserves further
      investigation as a potential cost-effective screening tool for the evaluation of
      patients with cirrhosis. The addition of 1- to 3-mm MPRs may increase specificity
      for risk stratification based on size measurements.

PMID- 21862807
TI  - Free-breathing 3D T1-weighted gradient-echo sequence with radial data sampling in
      abdominal MRI: preliminary observations.
AB  - OBJECTIVE: The purposes of this study were to evaluate the feasibility of a free
      breathing 3D gradient-recalled echo sequence with radial data sampling (radial 3D
      GRE) in abdominal MRI compared with a standard 3D GRE volumetric interpolated
      breath-hold examination (VIBE) sequence for imaging of cooperative patients and
      to perform a preliminary assessment in imaging of noncooperative patients.
      MATERIALS AND METHODS: Fifty-five consecutively registered patients who underwent
      unenhanced and contrast-enhanced abdominal MRI with the free-breathing radial 3D
      GRE technique constituted the study population. Two readers independently and
      blindly evaluated the images. RESULTS: Overall image quality with the contrast
      enhanced radial 3D GRE sequence was lower than but rated at least nearly as good
      as that with the 3D GRE VIBE sequence (p < 0.0001). Higher scores were recorded
      for 3D GRE VIBE images with respect to pixel graininess, streaking artifact, and
      sharpness (p = 0.0009 to p < 0.0001). Except for sharpness of vessels on
      unenhanced images, results for the radial 3D GRE sequence did not differ
      significantly in the comparison of cooperative and noncooperative patients (p =
      0.004). For imaging of noncooperative patients, radial 3D GRE images of children
      had higher ratings for shading (unenhanced, p = 0.0004; contrast-enhanced, p <
      0.0001) and streaking artifacts on contrast-enhanced images (p = 0.0017) than did
      those of adults. Overall image quality was higher for pediatric patients. In
      lesion analysis, use of the 3D GRE VIBE sequence was associated with
      significantly greater detectability, confidence, and conspicuity than was use of
      the radial 3D GRE sequence (p = 0.00026-0.011). CONCLUSION: A free-breathing
      radial 3D GRE sequence is feasible for abdominal MRI and may find application in
      imaging of patients who are unable to suspend respiration, especially children.

PMID- 21862808
TI  - Risk of nephrogenic systemic fibrosis in liver transplantation patients.
AB  - OBJECTIVE: The purpose of our study was to evaluate the exposure of our
      institution's liver transplantation population to gadolinium-based contrast
      agents and assess the rate of nephrogenic systemic fibrosis (NSF) within this
      unique group. MATERIALS AND METHODS: Institutional review board approval was
      obtained for a retrospective review of medical records of patients who had
      undergone liver transplantation at our institution between 1997 and 2008.
      Informed consent was not required. Demographic information, history of gadolinium
      based contrast agent exposure, stage of chronic kidney disease (CKD), and
      evidence of NSF were recorded. RESULTS: A total of 2142 patients who had
      undergone liver transplantation at our institution between 1997 and 2008 were
      identified. Of this total, 33% (709/2142) had documented gadolinium-based
      contrast agent exposure peritransplantation. Patients in CKD1 and 2, CKD3, CKD4,
      and CKD5 comprised 50% (352/709), 28% (200/709), 8% (60/709), and 14% (97/709),
      respectively. Of patients in CKD5, 76% (74/97) required dialysis. Thorough review
      of all patients' medical records identified one biopsy-confirmed case of NSF in
      the 709 patients. This patient was also in CKD5 and required dialysis.
      CONCLUSION: Within our institution, only 0.1% (1/709) of all liver
      transplantation patients exposed to gadolinium-based contrast agents or 1.4%
      (1/74) of CKD5 patients requiring dialysis had biopsy proof of NSF. This
      incidence is consistent with the rate of NSF in all patients exposed to
      gadolinium-based contrast agents regardless of liver transplantation reported in
      the literature. Therefore, liver transplantation may not be an independent risk
      factor in development of NSF in patients exposed to gadolinium-based contrast
      agents.

PMID- 21862809
TI  - Prostate cancer detection in patients with total serum prostate-specific antigen
      levels of 4-10 ng/mL: diagnostic efficacy of diffusion-weighted imaging, dynamic
      contrast-enhanced MRI, and T2-weighted imaging.
AB  - OBJECTIVE: The purpose of this study is to evaluate the utility of T2-weighted
      imaging, dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging
      (DWI) for detecting prostate cancer in patients with total serum prostate
      specific antigen (PSA) levels of 4-10 ng/mL, which is referred to as the "gray
      zone." MATERIALS AND METHODS: Fifty patients with gray-zone PSA levels underwent
      MRI before biopsy. According to the sites of biopsy, the prostate was divided
      into eight regions on MRI scans. These regions were evaluated individually for
      the following features: detectability of prostate cancer on per-region and per
      patient bases, and relationship between tumor size and positive or negative MRI
      findings for tumor detection. RESULTS: On a per-region basis, the sensitivity and
      specificity of tumor detection were 36% and 97% for T2-weighted imaging, 43% and
      95% for DCE-MRI, 38% and 96% for DWI, and 53% and 93% for the combined method of
      MRI, respectively. The sensitivity of combined MRI to detect tumor was
      significantly higher than those of the individual methods (p < 0.001 to p =
      0.001). Tumor size was significantly larger in regions with positive MRI findings
      than in regions with negative MRI findings (p = 0.004). On a per-patient basis,
      sensitivity and specificity of combined MRI to detect prostate cancer were 83%
      and 80%, respectively. CONCLUSION: Combined T2-weighted imaging, DWI, and DCE-MRI
      findings appear to be potentially useful for detecting and managing prostate
      cancer, even when performed for patients with gray-zone PSA levels.

PMID- 21862810
TI  - Incidence of multiple sporadic renal cell carcinomas in patients referred for
      renal radiofrequency ablation: implications for imaging follow-up.
AB  - OBJECTIVE: The objective of our study was to report the incidence of multiple
      sporadic primary renal cell carcinomas (RCCs) in patients referred for
      radiofrequency ablation (RFA). MATERIALS AND METHODS: A retrospective search
      identified 162 patients (104 men and 58 women; mean age, 74 years) without a
      history of von Hippel-Lindau disease with a total of 175 tumors treated with RFA
      for biopsy-proven primary renal malignancies at our institution from 1998 to
      2009. Three groups of patients with multiple RCCs were identified: patients with
      a history of nephrectomy for RCC who had been referred for RFA of a new renal
      tumor, patients who presented with multiple renal tumors at the time of referral
      for RFA, and patients who were shown to have developed a new renal tumor on
      follow-up imaging after RFA. RESULTS: Twenty-eight patients (17%) had multiple
      biopsy-proven RCCs. Eighteen patients (11%) had undergone prior nephrectomy for
      surgically proven RCC. The mean interval between prior nephrectomy and RFA
      referral was 122 months (range, 12-456 months). Seven patients (4%) without a
      history of nephrectomy presented with two biopsy-proven RCCs at RFA referral.
      Three patients (2%) who had not undergone nephrectomy and had a solitary RCC at
      the time of RFA had developed a new biopsy-proven RCC separate from the original
      treatment site on follow-up imaging after RFA. The mean time to diagnosis from
      the initial RFA treatment was 52 months (range, 25-89 months). CONCLUSION:
      Imaging surveillance of patients referred for renal RFA may be important not only
      to assess treatment success but also to detect new RCCs.

PMID- 21862811
TI  - MRI evaluation of urethral diverticula and differential diagnosis in symptomatic
      women.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of MRI in the
      diagnosis and differential diagnosis of urethral diverticula in symptomatic
      women. MATERIALS AND METHODS: Women referred for MRI at a single institution
      because of suspicion of urethral diverticula were included. All MRI examinations
      were independently evaluated by two radiologists and compared with patients'
      follow-up data. Sensitivity and specificity of MRI for urethral diverticula were
      calculated using surgery and clinical confirmation as the reference standards.
      Image quality of the urethra and periurethral region performed with the
      endoluminal coil was compared with the pelvic phased-array coil. RESULTS: From a
      study group of 60 patients (mean age, 44 years), 20 patients (33%) had urethral
      diverticula and 28 (47%) had an alternative diagnosis, of which 13 (46%) were
      visualized with MRI. In the remaining 12 patients (20%) no abnormalities were
      found. For urethral diverticula, MRI had both sensitivity and specificity of
      100%. Twenty patients had a total of 27 diverticula; these were mostly locally
      round (n = 12) with sharp margins (n = 25) and high (n = 19) homogeneous (n = 16)
      signal intensity on T2-weighted sequences. The ostium of urethral diverticula was
      identified in 23 diverticula (85%) by both readers. Agreement was 93% with kappa
      = 0.72. Endoluminal coil placement in the vagina showed the best image quality of
      the urethra and periurethral region. CONCLUSION: Dedicated MRI is an excellent
      imaging modality for urethral diverticula; furthermore, MRI will show the
      alternative diagnosis in almost one half of the remaining patients.

PMID- 21862812
TI  - Patient safety event reporting in a large radiology department.
AB  - OBJECTIVE: The purpose of this article is to describe our experience developing a
      Web-based radiology-specific event reporting system. CONCLUSION: The Web-based
      safety event reporting system has been a valuable tool permitting us to address
      potential safety concerns in our department.

PMID- 21862813
TI  - Dose reduction to anterior surfaces with organ-based tube-current modulation:
      evaluation of performance in a phantom study.
AB  - OBJECTIVE: The purpose of this study was to evaluate in phantoms the dose
      reduction to anterior surfaces and image quality with organ-based tube-current
      modulation in head and thoracic CT. MATERIALS AND METHODS: Organ-based tube
      current modulation is designed to reduce radiation dose to superficial
      radiosensitive organs, such as the lens of the eye, thyroid, and breast, by
      decreasing the tube current when the tube passes closest to these organs. Dose
      and image quality were evaluated in phantoms for clinical head and thorax
      examination protocols with and without organ-based tube-current modulation.
      Surface dose reduction as a function of position was measured using a 32-cm CT
      dose index (CTDI) phantom, an anthropomorphic adult phantom, and ion chambers.
      Surface dose reduction as a function of patient size was investigated using three
      semianthropomorphic phantoms with posteroanterior dimensions of 14, 25, and 31
      cm. Image noise (the SD of CT numbers in regions of interest) was evaluated for
      the anthropomorphic and the semianthropomorphic phantoms. RESULTS: For equivalent
      scanner output (volume CTDI), the dose to the midline of the anterior surface was
      reduced by 27-50%, depending on the anatomic region (head or thorax) and phantom
      size, and the dose to the posterior surface was correspondingly increased. Image
      noise was not significantly different between scans with and without organ-based
      tube-current modulation (p = 0.85). CONCLUSION: Organ-based tube-current
      modulation can reduce the dose to the anterior surface of patients without
      increasing image noise by commensurately increasing the dose to the posterior
      surface. This technique can reduce the dose to anterior radiosensitive organs for
      head and thoracic CT scans.

PMID- 21862814
TI  - Comparison of gadolinium-enhanced fat-saturated T1-weighted FLAIR and fast spin
      echo MRI of the spine at 3 T for evaluation of extradural lesions.
AB  - OBJECTIVE: Inversion recovery has been used to correct the loss of CSF and tissue
      contrast at 3 T versus 1.5 T but has not been formally investigated in the spine
      after IV administration of gadolinium-based contrast agent. The purpose of this
      study is to compare two sequences for gadolinium-enhanced spine imaging at 3 T-
      fat-saturated T1-weighted FLAIR and fat-saturated T1-weighted fast spin-echo
      (FSE)--for evaluation of extradural lesions and CSF-cord contrast. MATERIALS AND
      METHODS: After IV administration of gadolinium-based contrast agent, fat
      saturated T1-weighted FSE and FLAIR sequences were obtained in 156 MRI scans of
      143 patients at 3 T. Three experienced radiologists compared these sequences for
      conspicuity differences in bone lesions, disk lesions, other epidural lesions,
      and cord-CSF contrast. A 7-point visual rating scale was used, with lower numbers
      indicating increased conspicuity on gadolinium-enhanced fat-saturated T1-weighted
      FLAIR and higher numbers indicating increased conspicuity on gadolinium-enhanced
      fat-saturated T1-weighted FSE. RESULTS: A slight increase in the conspicuity of
      gadolinium-enhancing bone lesions (mean score, 3.6; p < 0.0001), disk lesions
      (mean score, 3.5; p < 0.0001), and epidural lesions (mean score, 3.4; p < 0.0001)
      was seen on fat-saturated T1-weighted FLAIR compared with fat-saturated T1
      weighted FSE. A higher degree of contrast between the spinal cord and CSF was
      seen on fat-saturated T1-weighted FLAIR, by a large margin (mean score, 1.8; p <
      0.0001). All enhancing lesions seen on fat-saturated T1-weighted FSE images were
      also seen on fat-saturated T1-weighted FLAIR images. CONCLUSION: Decreased CSF
      cord contrast at 3 T, as seen on T1-weighted FSE, can be regained by using T1
      weighted FLAIR. Fat-saturated T1-weighted FLAIR may increase conspicuity of
      gadolinium-enhancing extradural lesions compared with fat-saturated T1-weighted
      FSE.

PMID- 21862816
TI  - Skeletal scintigraphy with 18F-NaF PET for the evaluation of bone pain in
      children.
AB  - OBJECTIVE: Although not commonly used in current clinical practice, the PET agent
      (18)F-NaF provides an excellent alternative to the standard tracers used for
      radionuclide bone scintigraphy. This article illustrates the use and appearance
      of (18)F-NaF PET and shows examples of its utility in the assessment of bone pain
      in children. CONCLUSION: Skeletal imaging with (18)F-NaF harnesses both the
      superior imaging characteristics of PET and the improved biodistribution of the
      fluoride tracer in comparison with standard nuclear techniques, resulting in
      excellent-quality images that can effectively be used to investigate the cause of
      bone pain in children.

PMID- 21862815
TI  - Diffusion-tensor imaging assessment of white matter maturation in childhood and
      adolescence.
AB  - OBJECTIVE: The purpose of this study was to test a first hypothesis that
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values
      continue to change in late childhood and adolescence and a second hypothesis that
      less mature white matter (WM) regions have a higher rate of change than WM
      regions that are relatively more mature. SUBJECTS AND METHODS: Eighty-seven
      healthy children (50 girls, 37 boys; mean age, 11.2 +/- 3.6 years; range, 4.2
      17.7 years) underwent six-direction diffusion-tensor imaging with a 3-T MRI
      system. Three neuroradiologists independently drew regions of interest in 10 WM
      regions and measured FA and ADC values. To test the first hypothesis, we
      correlated these values with subject age by linear regression analysis (p <
      0.05). To test the second hypothesis, we determined whether regions with lower FA
      and higher ADC in the 4- to 7-year old group had a higher slope of FA increase
      and ADC decrease over the entire age range. For this assessment, we used linear
      regression analysis (p < 0.05) and curve fitting. RESULTS: In the test of the
      first hypothesis, increases in FA with age were noted in all WM regions and were
      statistically significant in six regions. Decreases in ADC values with age were
      noted in all brain regions except the genu of the corpus callosum. In all other
      regions except the splenium of the corpus callosum, the decreases were
      statistically significant. In the test of the second hypothesis, the relation
      between FA in the 4- to 7-year-old subjects and the FA increase in the entire
      sample was best described with a linear equation. The rate of age-related FA
      increase tended to be greater with lower initial FA (r = -0.384, p = 0.271). The
      relation between ADC in the 4- to 7-year-old subjects and ADC decrease in the
      entire population was best described with a second-order equation. The rate of
      age-related ADC decrease tended to be greater with higher initial ADC (r = 0.846,
      p = 0.001). For ADC values of 100 or less at age 4-7 years, the rate of ADC
      change with age tended to be decrease as initial ADC increased. CONCLUSION: In
      general, both hypotheses were verified. Overall, FA values continue to increase
      and ADC values continue to decrease during childhood and adolescence. The most
      rapid changes were found in WM regions that were least mature in the first few
      years of the study period.

PMID- 21862817
TI  - Intramuscular dexmedetomidine sedation for pediatric MRI and CT.
AB  - OBJECTIVE: Although dexmedetomidine has been administered to adults by
      intramuscular injection for perioperative anxiolysis and sedation, this route in
      children has not been described, to our knowledge. Our hypothesis was that
      intramuscular dexmedetomidine can be used to achieve sedation for MRI and CT of
      children. MATERIALS AND METHODS: The quality assurance data on all children who
      consecutively received intramuscular dexmedetomidine between August 1, 2007, and
      September 30, 2009, were reviewed. A single or repeated doses of 1-4 alphag/kg
      intramuscular dexmedetomidine had been administered to achieve a minimum Ramsay
      sedation score of 4. Patient demographics, medical diagnosis, vital signs,
      adverse events, and outcome measures were reviewed. RESULTS: Sixty-five children
      received consecutive intramuscular dexmedetomidine injections and successfully
      completed imaging studies. The MRI group received a total mean of 2.9 alphag/kg
      dexmedetomidine, and the CT group received a mean of 2.4 alphag/kg (p <= 0.01).
      There was no statistically significant relation between the total dose of
      dexmedetomidine received, mean time to achieve sedation (13.1-13.4 minutes), or
      time to meet discharge criteria after arrival in the recovery unit (17.1-21.9
      minutes). Nine patients (14%) experienced hypotension, defined as a decrease in
      blood pressure to less than 20% of the age-adjusted awake normal value. The
      dosage of dexmedetomidine was not a predictor of hypotension. None of the
      patients had bradycardia, hypertension, or oxygen desaturation. CONCLUSION: The
      intramuscular route is an alternative approach to dexmedetomidine delivery for
      pediatric sedation. Larger studies are warranted to evaluate the efficacy,
      safety, and hemodynamic outcome associated with the intramuscular use of
      dexmedetomidine in the care of children.

PMID- 21862818
TI  - Supplemental use of optical diffusion breast imaging for differentiation between
      benign and malignant breast lesions.
AB  - OBJECTIVE: The objective of our study was to prospectively evaluate the
      diagnostic accuracy of optical diffusion breast imaging in patients who underwent
      conventional ultrasound followed by surgery or biopsy. SUBJECTS AND METHODS: We
      performed optical diffusion breast imaging after conventional ultrasound of 193
      patients (mean age, 47 years) with 217 lesions. All patients underwent ultrasound
      guided core needle biopsy or surgery. One of six radiologists reviewed
      conventional ultrasound features, assessed a BI-RADS category, and reviewed
      optical diffusion imaging results for each lesion. Surgery and biopsy results
      were used as reference standards. We compared the diagnostic accuracy including
      the sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of conventional ultrasound alone and of conventional
      ultrasound followed by optical diffusion imaging. In addition, we prospectively
      investigated if total hemoglobin level or oxygen saturation level is the most
      reliable indicator in optical diffusion imaging. RESULTS: Of the 217 breast
      lesions, 108 were malignant and 109 were benign. For differentiation of malignant
      from benign lesions, conventional ultrasound was associated with a sensitivity of
      100%, specificity of 27.5%, PPV of 57.8%, NPV of 100%, and accuracy of 63.6%. The
      supplemental use of optical diffusion imaging after conventional ultrasound was
      associated with a sensitivity of 98.1%, specificity of 41.3%, PPV of 62.4%, NPV
      of 95.7%, and accuracy of 69.7%. The area under the receiver operating
      characteristic curve was 0.738 for total hemoglobin level and 0.502 for oxygen
      saturation level. The cutoff value was 0.195 mmol/L for total hemoglobin, with
      68.4% sensitivity and 69.7% specificity. CONCLUSION: Optical diffusion imaging
      might be a good supplemental tool to increase the diagnostic accuracy of
      conventional ultrasound in differentiating malignant from benign breast lesions.

PMID- 21862819
TI  - Flat epithelial atypia of the breast: pathological-radiological correlation.
AB  - OBJECTIVE: This study was undertaken to determine the prevalence of flat
      epithelial atypia at ultrasound-guided and stereotactically guided needle
      biopsies, to describe the mammographic and sonographic features of flat
      epithelial atypia, and to determine the significance of lesions diagnosed as flat
      epithelial atypia at imaging-guided needle biopsies. MATERIALS AND METHODS:
      Retrospective review of a database of 1369 consecutive sonographically and
      stereotactically guided needle biopsies performed during a 12-month period
      yielded 33 lesions with flat epithelial atypia as the most severe pathologic
      entity (32 patients). Two radiologists retrospectively reviewed the imaging
      presentation, by combined consensus, according to the BI-RADS lexicon. RESULTS:
      Twenty-two of 33 flat epithelial atypia diagnoses (67%) were obtained under
      stereotactic guidance, and 11 (33%) were obtained under sonographic guidance. Six
      patients had synchronous breast cancer. Flat epithelial atypia lesions presented
      mammographically most often as microcalcifications (20/33 [61%]) distributed in a
      cluster (14/20 [70%]) with amorphous morphology (13/20 [65%]). Sonographically,
      flat epithelial atypia lesions appeared most often as masses (9/11 [82%]), with
      an irregular shape (6/9 [67%]), microlobulated margins (5/9 [56%]), and
      hypoechoic or complex echotexture (7/9 [78%]). Twenty-eight of 33 lesions (85%)
      were surgically excised, confirming the flat epithelial atypia diagnosis in 11 of
      the 28 lesions (39%), yielding carcinoma in four (14%) and atypical ductal
      hyperplasia in six (21%). Columnar cell changes without atypia were diagnosed in
      four lesions (14%), and lobular carcinoma in situ was diagnosed in three lesions
      (11%). CONCLUSION: Mammographic and sonographic presentation of flat epithelial
      atypia is not specific (clustered amorphous microcalcifications and irregular,
      hypoechoic or complex masses). Given the underestimation rate of malignancy,
      surgical excision should be considered when imaging-guided biopsy yields flat
      epithelial atypia.

PMID- 21862820
TI  - Automated ultrasound of the breast for diagnosis: interobserver agreement on
      lesion detection and characterization.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate interobserver
      agreement on lesion detection and characterization in the review of automated
      ultrasound images of the breast by five radiologists. SUBJECTS AND METHODS: From
      August to October 2009, bilateral whole-breast ultrasound examinations were
      performed with an automated technique and with a handheld device for 55 women
      consecutively scheduled to undergo diagnostic ultrasound. Three-dimensional
      volume data from automated ultrasound were reviewed by five radiologists, who
      were unaware of the results of ultrasound with a handheld device and mammography
      and of the clinical information. If a lesion was detected with automated
      ultrasound, clock-face position, distance from the nipple, largest diameter, and
      BI-RADS final assessment category were evaluated. If the lesion was a mass,
      shape, orientation, margin, echogenicity, and posterior feature were analyzed.
      Intraclass correlation coefficients and kappa statistics were used for
      statistical analysis. RESULTS: At least two observers identified 145 lesions with
      automated ultrasound. Among 725 possible detections, 587 (81%) detections were
      made. Individual investigators detected between 74% (107/145) and 88% (127/145)
      of the lesions. The rate of detection of lesions larger than 1.2 cm was 92%. Most
      lesions detected only with handheld ultrasound (11/12, 92%) or automated
      ultrasound (34/36, 94%) were cysts or probably benign masses. All intraclass
      correlation coefficients for lesion location and size exceeded 0.75, indicating
      high reliability. Substantial agreement was found for mass shape (kappa = 0.71),
      orientation (kappa = 0.72), margin (kappa = 0.61), and BI-RADS final assessment
      category (kappa = 0.63). CONCLUSION: Detection of lesions larger than 1.2 cm in
      greatest diameter was reliable. High reliability was obtained for reporting
      lesion size and location. Substantial agreement was obtained for description of
      key feature and final assessment category.

PMID- 21862821
TI  - MRI features of stromal fibrosis of the breast with histopathologic correlation.
AB  - OBJECTIVE: The purpose of this article is to present the MRI features of stromal
      fibrosis of the breast, thus enabling radiologists to better determine radiologic
      pathologic concordance of biopsy results and appropriate patient management.
      MATERIALS AND METHODS: A retrospective review of radiology records between 2003
      and 2009 identified 123 MRI-detected lesions with the histologic diagnosis of
      stromal fibrosis. Of these, 83 cases were excluded either because stromal
      fibrosis was not the primary histologic diagnosis, or because there were
      associated pathologic abnormalities that may have contributed to contrast
      enhancement. The remaining 40 lesions with a primary histologic diagnosis of
      stromal fibrosis were included in our study. Their MRI and histopathologic
      features were examined and categorized. RESULTS: The lesions included five foci,
      23 masses, and 12 areas of nonmasslike enhancements. The prevalent features of
      the masses were size smaller than 1 cm (20/23 [87%]), round or oval shape (16/23
      [70%]), irregular or spiculated margins (15/23 [65%]), rapid or medium rate of
      initial contrast uptake (21/23 [91%]), and plateau or washout curves (16/23
      [70%]). Most nonmass lesions showed clumped enhancement (9/12) and linear
      distribution (7/12). Many of these features were suggestive of malignancy. Twenty
      seven of 40 cases (68%) had histologic confirmation by excision or MRI
      confirmation of benignancy. No false-negative cases have been identified to date.
      Histopathologic correlation showed the presence of masslike septal fibrosis
      associated with ectatic vascular channels in 60-67% of cases, which may lead to
      increased contrast enhancement on MRI. CONCLUSION: Stromal fibrosis has widely
      variable MRI features, often mimicking breast carcinoma. It may represent an
      acceptable benign concordant diagnosis on vacuum-assisted large-core needle
      biopsy for the described MRI findings.

PMID- 21862822
TI  - Sonographic confirmation of mammographic abnormality.

PMID- 21862823
TI  - Mammography-sonography concordance.

PMID- 21862824
TI  - Neighborhood context and social disparities in cumulative biological risk
      factors.
AB  - OBJECTIVE: This study examines the role of neighborhood context in the
      accumulation of biological risk factors and racial/ethnic and socioeconomic
      disparities. METHODS: Data came from face-to-face interviews and blood sample
      collection on a probability sample of adults (n = 549) in the 2002 Chicago
      Community Adult Health Study. Following the approach of prior studies, we
      constructed an index of cumulative biological risk (CBR) by counting how many of
      eight biomarkers exceeded clinically defined criteria for "high risk": systolic
      and diastolic blood pressure, resting heart rate, hemoglobin A(1c), C-reactive
      protein, waist size, and total and high-density lipoprotein cholesterol. Data are
      presented as incidence rate ratios (IRRs) based on generalized linear models with
      a Poisson link function and population-average estimates with robust standard
      errors. RESULTS: Non-Hispanic blacks (n = 200), Hispanics (n = 149), and people
      with low (n = 134) and moderate (n = 275) level of education had significantly
      higher numbers of biological risks than their respective reference groups (IRR =
      1.48, 1.59, 1.62, and 1.48, respectively, with p < .01). Black-white (p < .001)
      and Hispanic-white (p < .003) disparities in CBR remained significant after
      adjusting for individual-level socioeconomic position and behavioral factors,
      whereas individual-level controls substantially diminished the low/high (p <
      .069) and moderate/high (p < .042) educational differences. Estimating "within
      neighborhood" disparities to adjust for neighborhood context fully explained the
      black-white gap in CBR (p < .542) and reduced the Hispanic-white gap to
      borderline significance (p < .053). Neighborhood affluence predicted lower levels
      of CBR (IRR = 0.82, p < .027), but neighborhood disadvantage was not
      significantly associated with CBR (IRR = 1.00, p < .948). CONCLUSIONS:
      Neighborhood environments seem to play a pivotal role in the accumulation of
      biological risk and disparities therein.

PMID- 21862825
TI  - The nocebo effect and its relevance for clinical practice.
AB  - Negative expectations deriving from the clinical encounter can produce negative
      outcomes, known as nocebo effects. Specifically, research on the nocebo effect
      indicates that information disclosure about potential side effects can itself
      contribute to producing adverse effects. Neurobiological processes play a role in
      the nocebo effect, and this article provides a selective review of mechanistic
      research on the nocebo effect. Comparatively little attention has been directed
      to clinical studies and their implications for daily clinical practice. The
      nocebo response is influenced by the content and the way information is presented
      to patients in clinical trials in both the placebo and active treatment
      conditions. Nocebo effects adversely influence quality of life and therapy
      adherence, emphasizing the need for minimizing these responses to the extent
      possible. Evidence further indicates that the informed consent process in
      clinical trials may induce nocebo effects. This article concludes with ethical
      directions for future patient-oriented research and routine practice.

PMID- 21862826
TI  - Lack of prognostic value of type D personality for mortality in a large sample of
      heart failure patients.
AB  - BACKGROUND: Type D personality has been proposed as a prognostic indicator for
      mortality in cardiovascular disease. Most research examining this construct
      originates from one research group, and it is critical that the predictive value
      of Type D personality for adverse outcomes is independently cross-validated. This
      study examined its prognostic value in heart failure, relative to B-type
      natriuretic peptide (BNP) and depressive symptoms. METHODS: We studied 706
      patients with complete BNP, depressive symptom, and Type D personality and
      mortality data from 958 patients with heart failure enrolled after
      hospitalization for a multisite study of a disease management program.
      Multivariable models were adjusted for BNP and depression. RESULTS: At 18 months,
      there were 192 deaths (27.2%). No evidence was found for a prognostic value of
      Type D personality in the unadjusted model (hazard ratio [HR] = 0.893, 95%
      confidence interval [CI] = 0.582-1.370). In contrast, BNP was significantly
      predictive of mortality (HR = 1.588, 95% CI = 1.391-1.812), whereas depression
      was not (HR = 1.011, 95% CI = 0.998-1.024). Type D was also not predictive in
      covariate-adjusted models (HR = 0.779, 95% CI = 0.489-1.242). Similar results
      were obtained when analyzing Type D as the interaction between continuous z
      scores of its two components, negative affectivity and social inhibition (p =
      .144). CONCLUSIONS: In the largest study to date, Type D does not predict
      mortality. Future research should construe Type D as the interaction of
      continuous negative affectivity and social inhibition z scores, rather than as a
      typology, and consider analyses replacing negative affectivity with depression.

PMID- 21862827
TI  - Type D personality and all-cause mortality in cardiac patients--data from a
      German cohort study.
AB  - OBJECTIVE: Type D personality has been established as a predictor of adverse
      clinical events in patients with cardiovascular diseases. To date, all studies
      except one have been conducted by a single research group. Thus, the aim of our
      study was to provide an independent replication of the results regarding the
      prognostic validity of Type D personality in a German sample of cardiac patients.
      METHODS: Cardiac patients (n = 1040) were recruited from cardiac rehabilitation
      centers (n = 484), an outpatient clinic (n = 249), and a university hospital (n =
      307). Main analyses were based on the combined data from these three subsamples.
      Cardiac health status, medical risk factors, sociodemographic characteristics,
      psychological symptoms, and Type D personality were assessed at baseline. The
      primary end point was all-cause mortality. The Cox proportional hazards
      regression model was used to estimate the relative risk of death. RESULTS: Vital
      status was known for 977 patients (22.5% women; mean [standard deviation] = 63.3
      [10.7] years). Within the follow-up time (mean [standard deviation] = 71.5 [3.6]
      months), 172 patients died. Type D personality was found in 25.2% of survivors
      and in 22.2% of nonsurvivors (chi2= 0.78, p = .38). Depressive symptoms (p = .13)
      and anxiety (p = .27) were also not predictive of mortality. In the multivariate
      analyses, neither Type D (p = .95) nor negative affectivity (p = .71) and social
      inhibition (p = .59), as well as their interaction (p = .88), were associated
      with all-cause mortality. CONCLUSIONS: In the present study, Type D personality
      and its constituents are not associated with increased mortality in patients with
      heart disease. The discrepancies with previous results deserve further
      investigation.

PMID- 21862828
TI  - Neural substrates of decision making as measured with the Iowa Gambling Task in
      men with alexithymia.
AB  - OBJECTIVE: Individuals with alexithymia have a reduced ability to use their
      feelings to guide their behavior appropriately in social situations. To reveal
      the capacity to use emotional signals in alexithymia under conditions of
      uncertainty, this study investigates neural substrates and performance on the
      Iowa Gambling Task (IGT), which was developed to assess decision making based on
      emotion-guided evaluation. METHODS: The participants were 10 men with alexithymia
      and 13 without. Alexithymia was assessed by the 20-item Toronto Alexithymia
      Scale. Regional cerebral blood flow (rCBF) was measured by [15O]-H2O positron
      emission tomography during four trials of the IGT and two visuomotor control
      tasks. RESULTS: The participants with alexithymia failed to learn an advantageous
      decision-making strategy, with performance differing significantly from the
      nonalexithymic group in the fourth IGT trial (p = .029). Comparing performance
      between the IGT and the control tasks, both groups showed brain activation in the
      dorsolateral frontal area, inferior frontal lobe, pre-supplementary motor area,
      inferior parietal lobe, fusiform gyrus, and cerebellum. Men with alexithymia
      showed lower rCBF in the medial frontal area (Brodmann area [BA] 10) and higher
      rCBF in the caudate and occipital areas in the first and second IGT trials, which
      are within a learning phase according to test performance data. All brain data
      were significant at p <= .001, uncorrected. CONCLUSIONS: BA10 activity may be
      associated with using internal signals accompanying affective evaluation of the
      stimuli, which is crucial for successful decision making. Reduced BA10 activity
      in participants with alexithymia suggests that they may not use an emotion-based
      biasing signal to lead to advantageous decision making.

PMID- 21862830
TI  - Increased risks of acute organ dysfunction and mortality in intensive care unit
      patients with schizophrenia: a nationwide population-based study.
AB  - OBJECTIVE: To investigate the risks of acute organ dysfunction and death in
      intensive care unit (ICU) patients with schizophrenia. METHODS: Using a
      retrospective matched cohort design, we compared 203 schizophrenic patients to
      2036 demographically matched (1:10) nonschizophrenic patients with first-time ICU
      admission between 2005 and 2007 using the claims data of a nationally
      representative cohort from the Taiwan National Health Insurance Research
      Database. Definitions of schizophrenia and associated diagnoses were based on the
      codes of the International Classification of Diseases, Ninth Revision, Clinical
      Modification. Analyses were performed using univariate and multivariate analyses.
      RESULTS: The median age of schizophrenic patients was 53 years; 61.1% were men.
      Schizophrenic patients were less likely to be hospitalized in a medical center
      and had fewer surgical conditions and principal cardiovascular diagnoses, but
      they had a higher prevalence of infection than nonschizophrenic patients. After
      controlling for the aforementioned baseline covariates, schizophrenic patients
      had a higher risk of acute organ dysfunction (adjusted odds ratio = 1.52, 95%
      confidence interval = 1.09-2.10). When individual organ systems were analyzed,
      they had a 47% higher risk of respiratory dysfunction, a 194% higher risk of
      renal dysfunction, and a 122% higher risk of neurological dysfunction than
      nonschizophrenic patients. Hospital mortality was also higher in schizophrenic
      patients than in nonschizophrenic patients (24.1% versus 14.4%, p < .001;
      adjusted odds ratio = 1.56, 95% confidence interval = 1.08-2.24). CONCLUSIONS:
      Among ICU patients, schizophrenic patients were sicker, having a higher risk of
      acute organ dysfunction and death.

PMID- 21862831
TI  - Epidermoid cyst of the brainstem in children: case-based update.
AB  - Epidermoid cysts are rare, slow growing, space-occupying lesions of early
      adulthood. Among the various locations, involvement of the brainstem is quite
      exceptional. In children, these tumors are extremely uncommon; only 4 purely
      intrinsic brainstem epidermoids are reported in the literature. The pathogenesis
      of true intraaxial brainstem epidermoid is unclear and is usually not considered
      in the preoperative differential diagnosis of brainstem tumors. We report 2
      additional cases of brainstem epidermoid cysts occurring in children, underlining
      their clinical characteristics, the difficulties faced in the diagnostic work-up,
      and the surgical treatment adopted. These tumors pose a surgical challenge and
      attempts at aggressive removal of the cyst wall are fraught with increased risks
      of morbidity and mortality. On the other hand, cases treated more conservatively
      show good or excellent results with minimal complications. Neurosurgical judgment
      at the time of surgery is warranted to ensure maximum resection while minimizing
      postoperative neurologic deficits.

PMID- 21862829
TI  - Interacting effects of trait anger and acute anger arousal on pain: the role of
      endogenous opioids.
AB  - OBJECTIVE: Elevated trait anger (TRANG; heightened propensity to experience
      anger) is associated with greater pain responsiveness, possibly via associations
      with deficient endogenous opioid analgesia. This study tested whether acute anger
      arousal moderates the impact of TRANG on endogenous opioid analgesia. METHODS:
      Ninety-four chronic low back pain (LBP) participants and 85 healthy controls
      received opioid blockade (8 mg of naloxone) or placebo in a randomized,
      counterbalanced order in separate sessions. Participants were randomly assigned
      to undergo either a 5-minute anger recall interview (ARI) or a neutral control
      interview across both drug conditions. Immediately after the assigned interview,
      participants engaged sequentially in finger pressure and ischemic forearm pain
      tasks. Opioid blockade effects were derived (blockade minus placebo condition
      pain ratings) to index opioid antinociceptive function. RESULTS: Placebo
      condition TRANG by interview interactions (p values < .05) indicated that TRANG
      was hyperalgesic only in the context of acute anger arousal (ARI condition; p
      values < .05). Blockade effect analyses suggested that these hyperalgesic effects
      were related to deficient opioid analgesia. Significant TRANG by interview
      interactions (p values < .05) for both pain tasks indicated that elevated TRANG
      was associated with smaller blockade effects (less endogenous opioid analgesia)
      only in the ARI condition (p values < .05). Results for ischemic task visual
      analog scale intensity blockade effects suggested that associations between TRANG
      and impaired opioid function were most evident in LBP participants when
      experiencing anger (type by interview by TRANG interaction; p < .05).
      CONCLUSIONS: Results indicate that hyperalgesic effects of TRANG are most
      prominent when acute anger is aroused and suggest that endogenous opioid
      mechanisms contribute.

PMID- 21862832
TI  - BRAF gene deletion broadens the clinical spectrum neuro-cardio-facial-cutaneous
      syndromes.
AB  - Point mutations in the human BRAF gene are associated with a group of
      heterogeneous autosomal dominant neuro-cardio-facial-cutaneous syndromes. We
      identified a novel 93 kb intragenic deletion of the BRAF gene in a boy with
      severe developmental encephalopathy using microarray-based comparative genomic
      hybridization. The unique genotype and phenotype in this patient expands the
      spectrum of BRAF-related neurodevelopmental disorders. We propose a BRAF gene
      loss-of-function mechanism to best explain the biological basis of this severe
      developmental encephalopathy with postnatal growth deficiency.

PMID- 21862833
TI  - Two children with both arm ischemia and arterial ischemic stroke during the
      perinatal period.
AB  - It is rare for both limb ischemia and arterial ischemic stroke to occur in the
      same child during the perinatal period. Two children who appear to have had
      perinatal emboli to both an arm and a middle cerebral artery territory are
      presented here. One child required amputation of the ischemic limb below the
      shoulder, and the other required skin grafts to the distal ischemic fingers. Each
      of these children later received cerebral magnetic resonance imaging for
      evaluation of developmental delay and was found to have what appeared to be old
      perinatal arterial ischemic stroke. Both children were homozygous for the
      methylenetetrahydrofolate reductase C677T gene variant. Eight other children with
      perinatal limb ischemia and stroke were found on literature review; several also
      had delayed diagnosis of perinatal stroke. This report examines the approach to
      diagnosis and treatment in each of these and makes suggestions for the similar
      cases in the future.

PMID- 21862834
TI  - Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes
      affect clinical features in Aicardi-Goutieres syndrome.
AB  - Aicardi-Goutieres syndrome is a rare encephalopathy of mutational origin
      characterized by increased levels of interferon alpha in cerebrospinal fluid. The
      aim of this study was to explore the influence of different Aicardi-Goutieres
      syndrome genotypes on the clinical course of patients, seeking to identify
      specific gene expression profiles able to explain Aicardi-Goutieres syndrome
      phenotype differences. We detected the occurrence of Aicardi-Goutieres syndrome
      mutations in 21 patients and compared microarray gene-expression data of
      cerebrospinal fluid lymphocytes with clinical variables. The levels of interferon
      alpha in cerebrospinal fluid were high in all patients; we found differences in
      the expression of genes encoding for Toll-like receptor, endogenous RNases, T
      lymphocyte activation, angiogenesis inhibition, and peripheral interferon alpha
      production. These results indicate that further to interferon alpha production in
      the central nervous system, a variety of other pathogenic mechanisms is activated
      in Aicardi-Goutieres syndrome to various degrees in different patients, thus
      explaining the interindividual difference in Aicardi-Goutieres syndrome course.

PMID- 21862835
TI  - The cessation of continuous spike wave in slow-wave sleep following a temporal
      lobectomy.
AB  - The role of surgery in continuous spike wave in slow-wave sleep has not been
      robustly explored. The authors present a case of an 11-year-old boy with
      refractory partial seizures and continuous spike wave in slow-wave sleep who was
      treated with an anterior temporal lobectomy. His presurgical brain magnetic
      resonance imaging revealed right basal ganglia and thalamic infarcts and right
      mesial temporal sclerosis. Following surgery, he achieved seizure freedom,
      cessation of continuous spike wave in slow-wave sleep, and improved cognition.
      This case provides further evidence that epilepsy syndromes with generalized
      electrographic discharges can be secondary to focal pathology and potentially
      cured with resective surgery. The normalization of his sleep electroencephalogram
      following the anterior temporal lobectomy suggests that temporal lobe structures
      may be involved in the seizure network needed to generate continuous spike wave
      in slow-wave sleep.

PMID- 21862837
TI  - Cooperative dynamics.

PMID- 21862836
TI  - Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5
      carboxylcytosine: potential implications for active demethylation of CpG sites.
AB  - Thymine DNA glycosylase (TDG) excises T from G.T mispairs and is thought to
      initiate base excision repair (BER) of deaminated 5-methylcytosine (mC). Recent
      studies show that TDG, including its glycosylase activity, is essential for
      active DNA demethylation and embryonic development. These and other findings
      suggest that active demethylation could involve mC deamination by a deaminase,
      giving a G.T mispair followed by TDG-initiated BER. An alternative proposal is
      that demethylation could involve iterative oxidation of mC to 5
      hydroxymethylcytosine (hmC) and then to 5-formylcytosine (fC) and 5
      carboxylcytosine (caC), mediated by a Tet (ten eleven translocation) enzyme, with
      conversion of caC to C by a putative decarboxylase. Our previous studies suggest
      that TDG could excise fC and caC from DNA, which could provide another potential
      demethylation mechanism. We show here that TDG rapidly removes fC, with higher
      activity than for G.T mispairs, and has substantial caC excision activity, yet it
      cannot remove hmC. TDG excision of fC and caC, oxidation products of mC, is
      consistent with its strong specificity for excising bases from a CpG context. Our
      findings reveal a remarkable new aspect of specificity for TDG, inform its
      catalytic mechanism, and suggest that TDG could protect against fC-induced
      mutagenesis. The results also suggest a new potential mechanism for active DNA
      demethylation, involving TDG excision of Tet-produced fC (or caC) and subsequent
      BER. Such a mechanism obviates the need for a decarboxylase and is consistent
      with findings that TDG glycosylase activity is essential for active demethylation
      and embryonic development, as are mechanisms involving TDG excision of deaminated
      mC or hmC.

PMID- 21862838
TI  - One-dimensional deterministic transport in neurons measured by dispersion
      relation phase spectroscopy.
AB  - We studied the active transport of intracellular components along neuron
      processes using a new method developed in our laboratory: dispersion-relation
      phase spectroscopy. This method is able to quantitatively map spatially the
      heterogeneous dynamics of the concentration field of the cargos at submicron
      resolution without the need for tracking individual components. The results in
      terms of density correlation function reveal that the decay rate is linear in
      wavenumber, which is consistent with a narrow Lorentzian distribution of cargo
      velocity.

PMID- 21862840
TI  - Loop formation of microtubules during gliding at high density.
AB  - The microtubule cytoskeleton, including the associated proteins, forms a complex
      network essential to multiple cellular processes. Microtubule-associated motor
      proteins, such as kinesin-1, travel on microtubules to transport membrane bound
      vesicles across the crowded cell. Other motors, such as cytoplasmic dynein and
      kinesin-5, are used to organize the cytoskeleton during mitosis. In order to
      understand the self-organization processes of motors on microtubules, we
      performed filament-gliding assays with kinesin-1 motors bound to the cover glass
      with a high density of microtubules on the surface. To observe microtubule
      organization, 3% of the microtubules were fluorescently labeled to serve as
      tracers. We find that microtubules in these assays are not confined to two
      dimensions and can cross one other. This causes microtubules to align locally
      with a relatively short correlation length. At high density, this local alignment
      is enough to create 'intersections' of perpendicularly oriented groups of
      microtubules. These intersections create vortices that cause microtubules to form
      loops. We characterize the radius of curvature and time duration of the loops.
      These different behaviors give insight into how crowded conditions, such as those
      in the cell, might affect motor behavior and cytoskeleton organization.

PMID- 21862839
TI  - Model of myosin node aggregation into a contractile ring: the effect of local
      alignment.
AB  - Actomyosin bundles frequently form through aggregation of membrane-bound myosin
      clusters. One such example is the formation of the contractile ring in fission
      yeast from a broad band of cortical nodes. Nodes are macromolecular complexes
      containing several dozens of myosin-II molecules and a few formin dimers. The
      condensation of a broad band of nodes into the contractile ring has been
      previously described by a search, capture, pull and release (SCPR) model. In
      SCPR, a random search process mediated by actin filaments nucleated by formins
      leads to transient actomyosin connections among nodes that pull one another into
      a ring. The SCPR model reproduces the transport of nodes over long distances and
      predicts observed clump-formation instabilities in mutants. However, the model
      does not generate transient linear elements and meshwork structures as observed
      in some wild-type and mutant cells during ring assembly. As a minimal model of
      node alignment, we added short-range aligning forces to the SCPR model
      representing currently unresolved mechanisms that may involve structural
      components, cross-linking and bundling proteins. We studied the effect of the
      local node alignment mechanism on ring formation numerically. We varied the new
      parameters and found viable rings for a realistic range of values.
      Morphologically, transient structures that form during ring assembly resemble
      those observed in experiments with wild-type and cdc25-22 cells. Our work
      supports a hierarchical process of ring self-organization involving components
      drawn together from distant parts of the cell followed by progressive
      stabilization.

PMID- 21862841
TI  - Conformational changes, diffusion and collective behavior in monomeric kinesin
      based motility.
AB  - Molecular motors convert chemical energy into mechanical motion and power the
      transport of material within living cells; the motion of a motor is thought to be
      influenced by stochastic chemical state transitions of the molecule as well as
      intramolecular diffusion of one motor head seeking the next binding site.
      Existing models for the motility of single-headed monomeric motors that map the
      system to a simplified two-state Brownian ratchet have some predictive power, but
      in general are unable to elucidate the contributions of different molecular level
      processes to the overall effective parameters. In this work, we build a detailed
      molecular level model of monomeric kinesin motility that naturally incorporates
      conformational changes (power strokes) and biased diffusion. Our results predict
      that mean velocity is most sensitive to the power stroke size, while run length
      distribution is sensitive primarily to the strength of the microtubule bias
      potential with a weak dependence on power stroke that can be tuned by the
      strength of an applied load. In addition, we demonstrate that motor pairs
      attached to the same cargo can cooperatively function to increase motility in
      both the plus- and minus-end directions. These findings illustrate the importance
      of a detailed mechanochemical model for dissecting the contributions of
      microscopic parameters to monomeric kinesin dynamics.

PMID- 21862842
TI  - Protein-coat dynamics and cluster phases in intracellular trafficking.
AB  - Clustering of membrane proteins is a hallmark of biological membranes' lateral
      organization and crucial to their function. However, the physical properties of
      these protein aggregates remain poorly understood. Ensembles of coat proteins,
      the example considered here, are necessary for intracellular transport in
      eukaryotic cells. Assembly and disassembly rates for coat proteins involved in
      intracellular vesicular trafficking must be carefully controlled: their assembly
      deforms the membrane patch and drives vesicle formation, yet the protein coat
      must rapidly disassemble after vesiculation. Motivated by recent experimental
      findings for protein-coat dynamics, we study a dynamical Ising-type model for
      coat assembly and disassembly, and demonstrate how simple dynamical rules
      generate a robust, steady-state distribution of protein clusters (corresponding
      to intermediate budded shapes) and how cluster sizes are controlled by the
      kinetics. We interpret the results in terms of both vesiculation and the coupling
      to cargo proteins.

PMID- 21862844
TI  - How does the antagonism between capping and anti-capping proteins affect actin
      network dynamics?
AB  - Actin-based cell motility is essential to many biological processes. We built a
      simplified, three-dimensional computational model and subsequently performed
      stochastic simulations to study the growth dynamics of lamellipodia-like branched
      networks. In this work, we shed light on the antagonism between capping and anti
      capping proteins in regulating actin dynamics in the filamentous network. We
      discuss detailed mechanisms by which capping and anti-capping proteins affect the
      protrusion speed of the actin network and the rate of nucleation of filaments. We
      computed a phase diagram showing the regimes of motility enhancement and
      inhibition by these proteins. Our work shows that the effects of capping and anti
      capping proteins are mainly transmitted by modulation of the filamentous network
      density and local availability of monomeric actin. We discovered that the
      combination of the capping/anti-capping regulatory network with nucleation
      promoting proteins introduces robustness and redundancy in cell motility
      machinery, allowing the cell to easily achieve maximal protrusion speeds under a
      broader set of conditions. Finally, we discuss distributions of filament lengths
      under various conditions and speculate on their potential implication for the
      emergence of filopodia from the lamellipodial network.

PMID- 21862843
TI  - The emergence of sarcomeric, graded-polarity and spindle-like patterns in bundles
      of short cytoskeletal polymers and two opposite molecular motors.
AB  - We use linear stability analysis and numerical solutions of partial differential
      equations to investigate pattern formation in the one-dimensional system of short
      dynamic polymers and one (plus-end directed) or two (one is plus-end, another
      minus-end directed) molecular motors. If polymer sliding and motor gliding rates
      are slow and/or the polymer turnover rate is fast, then the polymer-motor bundle
      has mixed polarity and homogeneous motor distribution. However, if motor gliding
      is fast, a sarcomeric pattern with periodic bands of alternating polymer polarity
      separated by motor aggregates evolves. On the other hand, if polymer sliding is
      fast, a graded-polarity bundle with motors at the center emerges. In the presence
      of the second, minus-end directed motor, the sarcomeric pattern is more
      ubiquitous, while the graded-polarity pattern is destabilized. However, if the
      minus-end motor is weaker than the plus-end directed one, and/or polymer
      nucleation is autocatalytic, and/or long polymers are present in the bundle, then
      a spindle-like architecture with a sorted-out polarity emerges with the plus-end
      motors at the center and minus-end motors at the edges. We discuss modeling
      implications for actin-myosin fibers and in vitro and meiotic spindles.

PMID- 21862845
TI  - Computerized fetal heart rate analysis in labor: detection of intervals with un
      assignable baseline.
AB  - The fetal heart rate (FHR) is monitored during labor to assess fetal health. Both
      visual and computerized interpretations of the FHR depend on assigning a baseline
      to detect key features such as accelerations or decelerations. However, it is
      sometimes impossible to assign a baseline reliably, by eye or by numerical
      methods. To address this issue, we used the Oxford Intrapartum FHR Database to
      derive an algorithm based on the distribution of the FHR that detects heart rate
      intervals without a clear baseline. We aimed to recognize when a fetus cannot
      maintain its heart rate baseline and use this to assist computerized FHR
      analysis. Twenty-three FHR windows (15 min long) were used to develop the method.
      The algorithm was then validated by comparison with experts who classified 50 FHR
      windows into two groups: baseline assignable or un-assignable. The average
      agreement between experts (kappa = 0.76) was comparable to the agreement between
      method and experts (kappa = 0.67). The algorithm was used in 22 559 patients with
      intrapartum FHR records to retrospectively determine the incidence of intervals
      (defined as 15 min windows) that had un-assignable baselines. Sixty-six percent
      had one or more such episodes at some stage, most commonly after the onset of
      pushing (55%) and least commonly pre-labor (16%). These episodes are therefore
      relatively common. Their detection should improve the reliability of computerized
      analysis and allow further studies of what they signify clinically.

PMID- 21862846
TI  - Comparison of in vitro breast cancer visibility in analyser-based computed
      tomography with histopathology, mammography, computed tomography and magnetic
      resonance imaging.
AB  - High-resolution analyser-based X-ray imaging computed tomography (HR ABI-CT)
      findings on in vitro human breast cancer are compared with histopathology,
      mammography, computed tomography (CT) and magnetic resonance imaging. The HR ABI
      CT images provided significantly better low-contrast visibility compared with the
      standard radiological images. Fine cancer structures indistinguishable and
      superimposed in mammograms were seen, and could be matched with the
      histopathological results. The mean glandular dose was less than 1 mGy in
      mammography and 12-13 mGy in CT and ABI-CT. The excellent visibility of in vitro
      breast cancer suggests that HR ABI-CT may have a valuable role in the future as
      an adjunct or even alternative to current breast diagnostics, when radiation dose
      is further decreased, and compact synchrotron radiation sources become available.

PMID- 21862847
TI  - Nanocomposite characterization on multiple length scales using uSAXS.
AB  - Nanocomposites have great potential for the rational synthesis of tailored
      materials. However, the templating process that transfers the self-organized
      nanostructure of a block copolymer or other mesophase onto the functional
      material is by no means trivial, and often involves multiple steps, each of which
      presents its own chemical and physical challenges. As a result the nanocomposite
      may not be homogeneous, but can be phase-separated into various components which
      may feature their own specific microstructure. Here it is shown how scanning
      microbeam small-angle X-ray scattering (uSAXS) can be used to characterize a
      thermoset resol/poly(isoprene-block-ethylene oxide) nanocomposite on multiple
      length scales with respect to homogeneity and microphase separation.

PMID- 21862848
TI  - Measurement of angular distribution of soft X-ray radiation from thin targets in
      the tabletop storage ring MIRRORCLE-20SX.
AB  - The only available tabletop electron storage rings are the machines from the
      MIRRORCLE series. The electrons are accelerated in a microtron and injected into
      the storage ring. During its circulation, each electron passes through a tiny
      target many times, emitting a photon beam. Both the spectrum and the angular
      distribution of the radiation depend on the material, the thickness and the shape
      of the target. In this paper measured angular distributions of the radiation from
      several different targets in the magnetic field of the 20 MeV storage ring
      MIRRORCLE-20SX are presented. The detector comprises a 3 mm * 3 mm * 8.5 um
      plastic scintillator (PS) coupled to a photomultiplier by a bundle of optical
      fibers. The output of the photomultiplier is digitized by an IF converter. This
      detector is sensitive mostly to soft X-ray radiation, and its PS is moved by a
      mechanical system in a plane perpendicular to the radiation axis. The measured
      angular distributions for Mo and Sn targets contain an annulus which is
      attributed to transition radiation. The angular distributions for Al, carbon
      nanotube and diamond-like carbon (DLC) targets show some suppression of the
      radiation along the magnetic field. This is the first evidence of observation of
      the angular distribution of synchrotron Cherenkov radiation, which represents
      Cherenkov radiation in a magnetic field. The power radiated from the DLC target
      is estimated.

PMID- 21862849
TI  - SHADOW3: a new version of the synchrotron X-ray optics modelling package.
AB  - A new version of the popular X-ray tracing code SHADOW is presented. An important
      step has been made in restructuring the code following new computer engineering
      standards, ending with a modular Fortran 2003 structure and an application
      programming interface (API). The new code has been designed to be compatible with
      the original file-oriented SHADOW philosophy, but simplifying the compilation,
      installation and use. In addition, users can now become programmers using the
      newly designed SHADOW3 API for creating scripts, macros and programs; being able
      to deal with optical system optimization, image simulation, and also low
      transmission calculations requiring a large number of rays (>10(6)). Plans for
      future development and questions on how to accomplish them are also discussed.

PMID- 21862850
TI  - Automated sample-scanning methods for radiation damage mitigation and diffraction
      based centering of macromolecular crystals.
AB  - Automated scanning capabilities have been added to the data acquisition software,
      JBluIce-EPICS, at the National Institute of General Medical Sciences and the
      National Cancer Institute Collaborative Access Team (GM/CA CAT) at the Advanced
      Photon Source. A 'raster' feature enables sample centering via diffraction
      scanning over two-dimensional grids of simple rectangular or complex polygonal
      shape. The feature is used to locate crystals that are optically invisible owing
      to their small size or are visually obfuscated owing to properties of the sample
      mount. The raster feature is also used to identify the best-diffracting regions
      of large inhomogeneous crystals. Low-dose diffraction images taken at grid
      positions are automatically processed in real time to provide a quick quality
      ranking of potential data-collection sites. A 'vector collect' feature mitigates
      the effects of radiation damage by scanning the sample along a user-defined three
      dimensional vector during data collection to maximize the use of the crystal
      volume and the quality of the collected data. These features are integrated into
      the JBluIce-EPICS data acquisition software developed at GM/CA CAT where they are
      used in combination with a robust mini-beam of rapidly changeable diameter from 5
      um to 20 um. The powerful software-hardware combination is being applied to
      challenging problems in structural biology.

PMID- 21862851
TI  - Quantum critical point in SmO(1-x)F(x)FeAs and oxygen vacancy induced by high
      fluorine dopant.
AB  - The local lattice and electronic structure of the high-T(c) superconductor SmO(1
      x)F(x)FeAs as a function of F-doping have been investigated by Sm L(3)-edge X-ray
      absorption near-edge structure and multiple-scattering calculations. Experiments
      performed at the L(3)-edge show that the white line (WL) is very sensitive to F
      doping. In the under-doped region (x <= 0.12) the WL intensity increases with
      doping and then it suddenly starts decreasing at x = 0.15. Meanwhile, the trend
      of the WL linewidth versus F-doping levels is just contrary to that of the
      intensity. The phenomenon is almost coincident with the quantum critical point
      occurring in SmO(1-x)F(x)FeAs at x ? 0.14. In the under-doped region the increase
      of the intensity is related to the localization of Sm-5d states, while
      theoretical calculations show that both the decreasing intensity and the
      consequent broadening of linewidth at high F-doping are associated with the
      content and distribution of oxygen vacancies.

PMID- 21862852
TI  - The measurement of differential EXAFS modulated by high pressure.
AB  - Differential EXAFS (DiffEXAFS) is able to detect subtle atomic perturbations in
      the local area of the absorbing atom. Here a new method of performing DiffEXAFS
      experiments under the modulation of high pressure has been developed. Periodic
      pressure was achieved in the gasket with the help of a dynamic diamond anvil
      cell, and the measurements were conducted in common energy-scanning mode. This
      technique has been utilized on ZnSe at 4.8 GPa. The present results have
      demonstrated a good agreement with the equation of state of ZnSe, and revealed
      sensitivity to atomic displacements of one order higher in magnitude than that of
      conventional EXAFS.

PMID- 21862853
TI  - Effects of alkyl side chains on properties of aliphatic amino acids probed using
      quantum chemical calculations.
AB  - Effects of alkyl side chains (R-) on the electronic structural properties of
      aliphatic amino acids are investigated using quantum mechanical approaches. The
      carbon (C 1s) binding energy spectra of the aliphatic amino acids are derived
      from the C 1s spectrum of glycine (the parent spectrum) by the addition of
      spectral peaks, depending on the alkyl side chains, appearing in the lower energy
      region IP < 290 eV (where IP is the ionization potential). The two glycyl parent
      spectral peaks of the amide 291.0 eV [C((2))] and carboxylic 293.5 eV [C((1))] C
      atoms are shifted in the aliphatic amino acids owing to perturbations depending
      on the size and structure of the alkyl chains. The pattern of the N 1s and O 1s
      spectra in glycine is retained in the spectra of the other amino acids with small
      shifts to lower energy, again depending on the alkyl side chain. The Hirshfeld
      charge analyses confirm the observations. The alkyl effects on the valence
      binding energy spectra of the amino acids are concentrated in the middle valence
      energy region of 12-16 eV, and hence this energy region of 12-16 eV is considered
      as the 'fingerprint' of the alkyl side chains. Selected valence orbitals, either
      inside or outside of the alkyl fingerprint region, are presented using both
      density distributions and orbital momentum distributions, in order to understand
      the chemical bonding of the amino acids. It is also observed that the HOMO-LUMO
      energy gaps of the aliphatic amino acids are reduced with the growth of the alkyl
      side chain.

PMID- 21862854
TI  - X-ray tomography of morphological changes after freeze/thaw in gas diffusion
      layers.
AB  - Liquid water produced in a polymer electrolyte membrane fuel cell experiences a
      freeze/thaw cycle when the cell is switched off and on while operating at ambient
      temperatures below freezing. This freeze/thaw cycle permanently deforms the
      polymer electrolyte membrane fuel cell capillary structures and reduces both the
      cell life and its ability to generate electric power. The X-ray tomography
      facility at the Pohang Accelerator Laboratory was used to observe the freeze/thaw
      effects on the gas diffusion layer (GDL), which is the thickest capillary layer
      in the cell. Morphological changes in the GDL under a water freeze/thaw cycle
      were observed. A scenario in which freeze/thaw cycles affect fuel cell
      performance is suggested based on images from X-ray tomography.

PMID- 21862855
TI  - Two-dimensional approach to fluorescence yield XANES measurement using a silicon
      drift detector.
AB  - The objective of this article is to describe the capability of a two-dimensional
      (2D) approach to X-ray absorption near-edge structure (XANES) measurement by
      means of a partial fluorescence yield (PFY) method. 2D-XANES measurements were
      achieved by using a silicon drift detector as an energy-dispersive fluorescence
      detector. The advantage of this technique is that it allows full surveys of X-ray
      fluorescence data that are lost in conventional PFY measurements. The
      availability of a map approach was demonstrated by applying it to XANES
      measurements in both a diluted (Mn-doped nano-diamond) and a concentrated (MnO
      crystal) manganese sample. The 2D approach clearly distinguished between the PFY
      spectra of Mn and O atoms, where absorption edges of both elements are close to
      each other. Further, the 2D approach extracted an unambiguous PFY spectrum of
      phosphorus in the XANES measurement of SS304 (P < 0.045 wt%).

PMID- 21862856
TI  - In-line Bragg magnifier based on V-shaped germanium crystals.
AB  - In this work an X-ray imaging system based on a recently developed in-line two
      dimensional Bragg magnifier composed of two monolithic V-shaped crystals made of
      dislocation-free germanium is presented. The channel-cut crystals were used in
      one-dimensional and in two-dimensional (crossed) configurations in imaging
      applications and allowed measurement of phase-contrast radiograms both in the
      edge-enhanced and in the holographic regimes. The measurement of the phase
      gradient in two orthogonal directions is demonstrated. The effective pixel size
      attained was 0.17 um in the one-dimensional configuration and 0.5 um in the two
      dimensional setting, offering a twofold improvement in spatial resolution over
      devices based on silicon. These results show the potential for applying Bragg
      magnifiers to imaging soft matter at high resolution with reduced dose owing to
      the higher efficiency of Ge compared with Si.

PMID- 21862857
TI  - Carbon contamination of soft X-ray beamlines: dramatic anti-reflection coating
      effects observed in the 1 keV photon energy region.
AB  - Carbon contamination is a general problem of under-vacuum optics submitted to
      high fluence. In soft X-ray beamlines carbon deposit on optics is known to absorb
      and scatter radiation close to the C K-edge (280 eV), forbidding effective
      measurements in this spectral region. Here the observation of strong reflectivity
      losses is reported related to carbon deposition at much higher energies around
      1000 eV, where carbon absorptivity is small. It is shown that the observed effect
      can be modelled as a destructive interference from a homogeneous carbon thin
      film.

PMID- 21862858
TI  - European research platform IPANEMA at the SOLEIL synchrotron for ancient and
      historical materials.
AB  - IPANEMA, a research platform devoted to ancient and historical materials
      (archaeology, cultural heritage, palaeontology and past environments), is
      currently being set up at the synchrotron facility SOLEIL (Saint-Aubin, France;
      SOLEIL opened to users in January 2008). The new platform is open to French,
      European and international users. The activities of the platform are centred on
      two main fields: increased support to synchrotron projects on ancient materials
      and methodological research. The IPANEMA team currently occupies temporary
      premises at SOLEIL, but the platform comprises construction of a new building
      that will comply with conservation and environmental standards and of a hard X
      ray imaging beamline today in its conceptual design phase, named PUMA. Since
      2008, the team has supported synchrotron works at SOLEIL and at European
      synchrotron facilities on a range of topics including pigment degradation in
      paintings, composition of musical instrument varnishes, and provenancing of
      medieval archaeological ferrous artefacts. Once the platform is fully
      operational, user support will primarily take place within medium-term research
      projects for 'hosted' scientists, PhDs and post-docs. IPANEMA methodological
      research is focused on advanced two-dimensional/three-dimensional imaging and
      spectroscopy and statistical image analysis, both optimized for ancient
      materials.

PMID- 21862859
TI  - Three-dimensional imaging of chemical phase transformations at the nanoscale with
      full-field transmission X-ray microscopy.
AB  - The ability to probe morphology and phase distribution in complex systems at
      multiple length scales unravels the interplay of nano- and micrometer-scale
      factors at the origin of macroscopic behavior. While different electron- and X
      ray-based imaging techniques can be combined with spectroscopy at high
      resolutions, owing to experimental time limitations the resulting fields of view
      are too small to be representative of a composite sample. Here a new X-ray
      imaging set-up is proposed, combining full-field transmission X-ray microscopy
      (TXM) with X-ray absorption near-edge structure (XANES) spectroscopy to follow
      two-dimensional and three-dimensional morphological and chemical changes in large
      volumes at high resolution (tens of nanometers). TXM XANES imaging offers
      chemical speciation at the nanoscale in thick samples (>20 um) with minimal
      preparation requirements. Further, its high throughput allows the analysis of
      large areas (up to millimeters) in minutes to a few hours. Proof of concept is
      provided using battery electrodes, although its versatility will lead to impact
      in a number of diverse research fields.

PMID- 21862860
TI  - Radiation damage reveals promising interaction position.
AB  - High-resolution structural data of protein inhibitor complexes are the key to
      rational drug design. Synchrotron radiation allows for atomic resolutions but is
      frequently accompanied by radiation damage to protein complexes. In this study a
      human aldose reductase mutant complexed with a bromine-substituted inhibitor was
      determined to atomic resolution [Protein Data Bank (PDB) code 3onc]. Though the
      radiation dose was moderate, a selective disruption of a bromine-inhibitor bond
      during the experiment was observed while the protein appears unaffected. A
      covalent bond to bromine is cleaved and the displaced atom is not scattered
      throughout the crystal but can most likely be assigned as a bromide to an
      additional difference electron density peak observed in the structure. The
      bromide relocates to an adjacent unoccupied site where promising interactions to
      protein residues stabilize its position. These findings were verified by a second
      similar structure determined with considerably higher radiation dose (PDB code
      3onb).

PMID- 21862861
TI  - Microprobing the molecular spatial distribution and structural architecture of
      feed-type sorghum seed tissue (Sorghum Bicolor L.) using the synchrotron
      radiation infrared microspectroscopy technique.
AB  - Sorghum seed (Sorghum bicolor L.) has unique degradation and fermentation
      behaviours compared with other cereal grains such as wheat, barley and corn. This
      may be related to its cell and cell-wall architecture. The advanced synchrotron
      radiation infrared microspectroscopy (SR-IMS) technique enables the study of cell
      or living cell biochemistry within cellular dimensions. The objective of this
      study was to use the SR-IMS imaging technique to microprobe molecular spatial
      distribution and cell architecture of the sorghum seed tissue comprehensively.
      High-density mapping was carried out using SR-IMS on beamline U2B at the National
      Synchrotron Light Source (Brookhaven National Laboratory, NY, USA). Molecular
      images were systematically recorded from the outside to the inside of the seed
      tissue under various chemical functional groups and their ratios [peaks at ~1725
      (carbonyl C=O ester), 1650 (amide I), 1657 (protein secondary structure alpha
      helix), 1628 (protein secondary structure beta-sheet), 1550 (amide II), 1515
      (aromatic compounds of lignin), 1428, 1371, 1245 (cellulosic compounds in plant
      seed tissue), 1025 (non-structural CHO, starch granules), 1246 (cellulosic
      material), 1160 (CHO), 1150 (CHO), 1080 (CHO), 930 (CHO), 860 (CHO), 3350 (OH and
      NH stretching), 2960 (CH(3) anti-symmetric), 2929 (CH(2) anti-symmetric), 2877
      (CH(3) symmetric) and 2848 cm(-1) (CH(2) asymmetric)]. The relative protein
      secondary structure alpha-helix to beta-sheet ratio image, protein amide I to
      starch granule ratio image, and anti-symmetric CH(3) to CH(2) ratio image were
      also investigated within the intact sorghum seed tissue. The results showed
      unique cell architecture, and the molecular spatial distribution and intensity in
      the sorghum seed tissue (which were analyzed through microprobe molecular
      imaging) were generated using SR-IMS. This imaging technique and methodology has
      high potential and could be used for scientists to develop specific cereal grain
      varieties with targeted food and feed quality, and can also be used to monitor
      the degree of grain maturity, grain damage, the fate of organic contaminants and
      the effect of chemical treatment on plant and grain seeds.

PMID- 21862862
TI  - Milli-electronvolt monochromatization of hard X-rays with a sapphire
      backscattering monochromator.
AB  - A sapphire backscattering monochromator with 1.1 (1) meV bandwidth for hard X
      rays (20-40 keV) is reported. The optical quality of several sapphire crystals
      has been studied and the best crystal was chosen to work as the monochromator.
      The small energy bandwidth has been obtained by decreasing the crystal volume
      impinged upon by the beam and by choosing the crystal part with the best quality.
      The monochromator was tested at the energies of the nuclear resonances of (121)Sb
      at 37.13 keV, (125)Te at 35.49 keV, (119)Sn at 23.88 keV, (149)Sm at 22.50 keV
      and (151)Eu at 21.54 keV. For each energy, specific reflections with sapphire
      temperatures in the 150-300 K region were chosen. Applications to nuclear
      inelastic scattering with these isotopes are demonstrated.

PMID- 21862863
TI  - Application of X-ray fluorescence to turbulent mixing.
AB  - Combined measurements of X-ray absorption and fluorescence have been performed in
      jets of pure and diluted argon gas to demonstrate the feasibility of using X-ray
      fluorescence to study turbulent mixing. Measurements show a strong correspondence
      between the absorption and fluorescence measurements for high argon
      concentration. For lower argon concentration, fluorescence provides a much more
      robust measurement than absorption. The measurements agree well with the accepted
      behavior of turbulent jets.

PMID- 21862864
TI  - Design of an anaerobic sample chamber for fluorescence measurements compatible
      with the Lytle detector.
AB  - A sample chamber has been developed that is compatible with the commercially
      available Lytle ion chamber with soller slits. The key features are (i) the
      sample position can be shifted vertically without changing the geometry with
      respect to the soller slits and ion chamber, (ii) the gas-tight structure makes
      it possible for experiments to work with samples that require anaerobic
      conditions.

PMID- 21862867
TI  - Algae as promising organisms for environment and health.
AB  - Algae, like other plants, produce a variety of remarkable compounds collectively
      referred to as secondary metabolites. They are synthesized by these organisms at
      the end of the growth phase and/or due to metabolic alterations induced by
      environmental stress conditions. Carotenoids, phenolic compounds,
      phycobiliprotein pigments, polysaccharides and unsaturated fatty acids are same
      of the algal natural products, which were reported to have variable biological
      activities, including antioxidant activity, anticancer activity, antimicroabial
      activity against bacteria-virus-algae-fungi, organic fertilizer and
      bioremediation potentials.

PMID- 21862869
TI  - Stem cell aging and cancer: immortal but vulnerable.

PMID- 21862868
TI  - Using transgenic modulation of protein synthesis and accumulation to probe
      protein signaling networks in Arabidopsis thaliana.
AB  - Deployment of new model species in the plant biology community requires the
      development and/or improvement of numerous genetic tools. Sequencing of the
      Arabidopsis thaliana genome opened up a new challenge of assigning biological
      function to each gene. As many genes exhibit spatiotemporal or other conditional
      regulation of biological processes, probing for gene function necessitates
      applications that can be geared toward temporal, spatial and quantitative
      functional analysis in vivo. The continuing quest to establish new platforms to
      examine plant gene function has resulted in the availability of numerous genomic
      and proteomic tools. Classical and more recent genome-wide experimental
      approaches include conventional mutagenesis, tagged DNA insertional mutagenesis,
      ectopic expression of transgenes, activation tagging, RNA interference and two
      component transactivation systems. The utilization of these molecular tools has
      resulted in conclusive evidence for the existence of many genes, and expanded
      knowledge on gene structure and function. This review covers several molecular
      tools that have become increasingly useful in basic plant research. We discuss
      their advantages and limitations for probing cellular protein function while
      emphasizing the contributions made to lay the fundamental groundwork for genetic
      manipulation of crops using plant biotechnology.

PMID- 21862870
TI  - Bax is necessary for PGC1alpha pro-apoptotic effect in colorectal cancer cells.
AB  - We have recently shown that the transcriptional coactivator PGC1alpha, a master
      regulator of mitochondrial biogenesis and function, is involved in the control of
      the intestinal epithelium cell fate. Furthermore, PGC1alpha protects against
      colon cancer formation by promoting ROS accumulation and, consequently,
      mitochondria-mediated apoptosis. Here we provide an additional mechanistic
      insight into the tumor suppressor activity of PGC1alpha showing that its pro
      apoptotic effect is mediated by Bax. In fact, PGC1alpha overexpression in HCT116
      Bax (-/-) colorectal cancer cells stimulates mitochondrial production and
      activity, but it fails to induce cell death as well as to oppose tumor growth in
      the xenograft model. The lack of ROS accumulation in the Bax (-/-) cells
      strengthens our view that the PGC1alpha-induced oxidative burst represents one of
      the main apoptosis-driving factors in colorectal cancer cells.

PMID- 21862872
TI  - Potent anti-proliferative effects of metformin on trastuzumab-resistant breast
      cancer cells via inhibition of erbB2/IGF-1 receptor interactions.
AB  - We have shown that erbB2 altered breast cancer cells are less sensitive to the
      anti-proliferative effects of metformin than triple negative cells, and have
      described the differences of molecular mechanisms of metformin action by tumor
      subtypes. We hypothesized that metformin may be more effective against
      trastuzumab-resistant erbB2-overexpressing breast cancer cells because it targets
      the critical signaling pathways that are altered with resistance. BT474, SKBR3
      and derived trastuzumab-resistant sublines BT474-HR20 (HR20) and SKBR3-pool2
      (pool2) were used to test this hypothesis. Metformin treatment resulted in
      significantly more inhibition of proliferation and clonogenicity in resistant
      sublines. It decreased erbB2/insulin-like growth factor-1 receptor (IGF-1R)
      complexes (present only in the resistant sublines) without altering erbB2
      expression, and reduced the expression and activity of erbB3 and IGF-1R in the
      trastuzumab-resistant but not parental cells. Trastuzumab-resistant sublines were
      resistant to rapamycin induced changes in mTOR activity and cell growth. In
      contrast, both BT474 and HR20 cells were highly sensitive to inhibitors of Src
      (Dasatinib) and PI-3K (LY294002). The pool2 cells showed higher sensitivity than
      SKBR3 cells to LY294002, but not Dasatinib. On the basis of these data, metformin
      appears to be significantly more effective against trastuzumab-resistant as
      compared to sensitive breast cancer cells. Metformin disrupts erbB2/IGF-1R
      complexes, erbB3 and IGF-1R expression and activity, as well as Src kinase and/or
      PI-3K/Akt signaling. This action appears to be independent of mTOR signaling. Our
      findings provide a rationale to study the effects of metformin on patients with
      erbB2 positive tumors treated with trastuzumab, with or without resistance.

PMID- 21862871
TI  - Structural and mechanistic commonalities of amyloid-beta and the prion protein.
AB  - Amyloid beta (Abeta) is a major causative agent of Alzheime disease. This
      neurotoxic peptide is generated as a result of the cleavage of the Amyloid
      Precursor-Protein (APP) by the action of beta secretase and gamma secretase. The
      neurotoxicity was previously thought to be the result of aggregation. However,
      recent studies suggest that the interaction of Abeta with numerous cell surface
      receptors such as N-methyl-D-aspartate (NMDA), receptor for advanced
      glycosylation end products (RAGE), P75 neurotrophin receptor (P75NTR) as well as
      cell surface proteins such as the cellular prion protein (PrP(c) ) and heparan
      sulfate proteoglycans (HSPG) strongly enhances Abeta induced apoptosis and
      thereby contributes to neurotoxicity. This review focuses on the molecular
      mechanism resulting in Abeta-shedding as well as Abeta-induced apoptotic
      processes, genetic risk factors for familial Alzheimer disease and interactions
      of Abeta with cell surface receptors and proteins, with particular emphasis on
      the cellular prion protein. Furthermore, comparisons are drawn between Alzheimer
      disease and prion disorders and the role of laminin, an extracellular matrix
      protein, glycosaminoglycans and the 37 kDa/67 kDa laminin receptor (LRP/LR) have
      been highlighted with regards to both neurodegenerative diseases.

PMID- 21862873
TI  - Cox-2 inhibitors induce early c-Myc downregulation and lead to expression of
      differentiation markers in leukemia cells.
AB  - It is well described that cyclooxygenase-2 (COX-2) inhibitors counteract cancer
      cell proliferation by preventing the G1/S transition. This effect has been
      associated with the inhibition of COX-2 enzymatic activity but also as an off
      target effect essentially in adherent cancer cell models. In this study, we
      investigated the effect of three COX-2 inhibitors (nimesulide, NS-398 and
      celecoxib) on cell proliferation of leukemic and lymphoblastic cells expressing
      COX-2 at high (U937, Jurkat, Hel and Raji) and very low (K562) protein levels. We
      found that the inhibitors reduce cell proliferation in all COX-2-expressing cells
      leading to an accumulation in the G0/G1 phase of the cell cycle. We provide
      evidence that this modulation corresponds to an accumulation of cells in G0
      paralleled by the expression of cell differentiation markers in U937 (CD15) and
      Hel (CD41a and CD61) cells but not in the insensitive K562. These events are
      associated with a rapid down-regulation (within one hour) of c-Myc expression,
      accompanied by the up-regulation of p27 and the down-regulation of PCNA and
      cyclin D1. Our study suggests c-Myc as a crucial early target of COX-2
      inhibitors.

PMID- 21862875
TI  - Inhibition of activated pericentromeric SINE/Alu repeat transcription in
      senescent human adult stem cells reinstates self-renewal.
AB  - Cellular aging is linked to deficiencies in efficient repair of DNA double strand
      breaks and authentic genome maintenance at the chromatin level. Aging poses a
      significant threat to adult stem cell function by triggering persistent DNA
      damage and ultimately cellular senescence. Senescence is often considered to be
      an irreversible process. Moreover, critical genomic regions engaged in persistent
      DNA damage accumulation are unknown. Here we report that 65% of naturally
      occurring repairable DNA damage in self-renewing adult stem cells occurs within
      transposable elements. Upregulation of Alu retrotransposon transcription upon ex
      vivo aging causes nuclear cytotoxicity associated with the formation of
      persistent DNA damage foci and loss of efficient DNA repair in pericentric
      chromatin. This occurs due to a failure to recruit of condensin I and cohesin
      complexes. Our results demonstrate that the cytotoxicity of induced Alu repeats
      is functionally relevant for the human adult stem cell aging. Stable suppression
      of Alu transcription can reverse the senescent phenotype, reinstating the cells'
      self-renewing properties and increasing their plasticity by altering so-called
      "master" pluripotency regulators.

PMID- 21862874
TI  - Tracking the intermediate stages of epithelial-mesenchymal transition in
      epithelial stem cells and cancer.
AB  - Epithelial-mesenchymal transition (EMT) is an essential developmental program
      that becomes reactivated in adult tissues to promote the progression of cancer.
      EMT has been largely studied by examining the beginning epithelial state or the
      ending mesenchymal state without studying the intermediate stages. Recent studies
      using trophoblast stem (TS) cells paused in EMT have defined the molecular and
      epigenetic mechanisms responsible for modulating the intermediate "metastable"
      stages of EMT. Targeted inactivation of MAP3K4, knockdown of CBP, or
      overexpression of SNAI1 in TS cells induced similar metastable phenotypes. These
      TS cells exhibited epigenetic changes in the histone acetylation landscape that
      cause loss of epithelial maintenance while preserving self-renewal and
      multipotency. A similar phenotype was found in claudin-low breast cancer cells
      with properties of EMT and stemness. This intersection between EMT and stemness
      in TS cells and claudin-low metastatic breast cancer demonstrates the usefulness
      of developmental EMT systems to understand EMT in cancer.

PMID- 21862876
TI  - Crosstalk between MYCN and MDM2-p53 signal pathways regulates tumor cell growth
      and apoptosis in neuroblastoma.
AB  - Previous studies show that the MYCN and MDM2-p53 signal pathways are mutually
      regulated: MYCN stimulates MDM2 and p53 transcription, whereas MDM2 stabilizes
      MYCN mRNA and induces its translation. Herein, we report that the interaction
      between MDM2 and MYCN plays a critical role in MYCN-amplified neuroblastoma tumor
      cell growth and survival. Distinct from the known role that MDM2 has in
      regulating tumor promotion in non-MYCN-amplified neuroblastoma, in which MDM2
      inhibits p53, we found that MDM2 stimulated tumor growth in MYCN-amplified
      neuroblastoma in a p53-independent manner. In MYCN-amplified neuroblastoma cells,
      enforced expression of MDM2 further enhanced MYCN expression, yet no p53
      inhibition was observed by MDM2 due to upregulation of MYCN that stimulated p53
      transcription. Similarly, p53 expression remained unchanged in MDM2-silenced MYCN
      amplified neuroblastoma cells because MDM2 inhibition resulted in a
      downregulation of MYCN that decreased p53 transcription, although the MDM2
      mediated degradation of p53 was reduced. Also, we found that the enforced
      overexpression of MDM2, or conversely, the inhibition of overexpressed endogenous
      MDM2, led to either a remarkable increase or decrease in tumor growth,
      respectively, in MYCN-amplified neuroblastoma (even though no p53 function was
      involved). These results suggest that p53 that is reciprocally regulated by MDM2
      and MYCN is dispensable for suppression of MYCN-amplified neuroblastoma, and that
      the direct interaction between MDM2 and MYCN may contribute significantly to MYCN
      amplified neuroblastoma growth and disease progression.

PMID- 21862878
TI  - In search of housekeeping pathways that regulate longevity.

PMID- 21862883
TI  - THIS MONTH IN Anesthesiology.

PMID- 21862879
TI  - GABARAPL1 antibodies: target one protein, get one free!
AB  - Atg8 is a yeast protein involved in the autophagic process and in particular in
      the elongation of autophagosomes. In mammals, several orthologs have been
      identified and are classed into two subfamilies: the LC3 subfamily and the
      GABARAP subfamily, referred to simply as the LC3 or GABARAP families. GABARAPL1
      (GABARAP-like protein 1), one of the proteins belonging to the GABARAP (GABA(A)
      receptor-associated protein) family, is highly expressed in the central nervous
      system and implicated in processes such as receptor and vesicle transport as well
      as autophagy. The proteins that make up the GABARAP family demonstrate
      conservation of their amino acid sequences and protein structures. In humans,
      GABARAPL1 shares 86% identity with GABARAP and 61% with GABARAPL2 (GATE-16). The
      identification of the individual proteins is thus very limited when working in
      vivo due to a lack of unique peptide sequences from which specific antibodies can
      be developed. Actually, and to our knowledge, there are no available antibodies
      on the market that are entirely specific to GABARAPL1 and the same may be true of
      the anti-GABARAP antibodies. In this study, we sought to examine the specificity
      of three antibodies targeted against different peptide sequences within
      GABARAPL1: CHEM-CENT (an antibody raised against a short peptide sequence within
      the center of the protein), PTG-NTER (an antibody raised against the N-terminus
      of the protein) and PTG-FL (an antibody raised against the full-length protein).
      The results described in this article demonstrate the importance of testing
      antibody specificity under the conditions for which it will be used
      experimentally, a caution that should be taken when studying the expression of
      the GABARAP family proteins.

PMID- 21862877
TI  - Early behavioral changes and quantitative analysis of neuropathological features
      in murine prion disease: stereological analysis in the albino Swiss mice model.
AB  - Behavioral and neuropathological changes have been widely investigated in murine
      prion disease but stereological based unbiased estimates of key neuropathological
      features have not been carried out. After injections of ME7 infected (ME7) or
      normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6,
      we assessed behavioral changes on hippocampal-dependent tasks. We also estimated
      by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total
      number of neurons, reactive astrocytes, activated microglia and perineuronal nets
      (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino
      Swiss mice. On average, early behavioral changes in albino Swiss mice start four
      weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data
      in albino Swiss mice revealed that four of nine subjects start to change their
      behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining
      subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated
      dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal
      degeneration, and stereological data showed that early astrocytosis, microgliosis
      and reduction in the perineuronal nets are independent of a change in the number
      of neuronal cell bodies. Statistical analysis revealed that the septal region had
      greater levels of neuroinflammation and extracellular matrix damage than CA1.
      This stereological and multivariate analysis at early stages of disease in an
      outbred model of prion disease provided new insights connecting behavioral
      changes and neuroinflammation and seems to be important to understand the
      mechanisms of prion disease progression.

PMID- 21862884
TI  - Block-ing Pain with Jiffy Toothache Drops.

PMID- 21862886
TI  - The McMechans Telegram Erdmann on October 17, 1930.

PMID- 21862885
TI  - Volatile anesthetics protect cancer cells against tumor necrosis factor-related
      apoptosis-inducing ligand-induced apoptosis via caveolins.
AB  - BACKGROUND: Volatile anesthetics have a dual effect on cell survival dependent on
      caveolin expression. The effect of volatile anesthetics on cancer cell survival
      and death after anesthetic exposure has not been well investigated. The authors
      examined the effects of isoflurane exposure on apoptosis and its regulation by
      caveolin-1 (Cav-1). METHODS: The authors exposed human colon cancer cell lines to
      isoflurane and proapoptotic stimuli and assessed what role Cav-1 plays in cell
      protection. They evaluated apoptosis using assays for nucleosomal fragmentation,
      cleaved caspase 3 expression, and caspase activity assays. To test the mechanism,
      they used pharmacologic inhibitors (i.e., pertussis toxin) and assessed changes
      in glycolysis. RESULTS: Apoptosis as measured by nucleosomal fragmentation was
      enhanced by isoflurane (1.2% in air) in HT29 (by 64% relative to control, P <
      0.001) and decreased in HCT116 (by 23% relative to control, P < 0.001) cells.
      Knockdown of Cav-1 in HCT116 cells increased the sensitivity to apoptotic stimuli
      but not with scrambled small interfering RNA (siRNA) treatment (19.7 +/- 0.4 vs.
      20.0 +/- 0.6, P = 0.7786 and 19.7 +/- 0.5 vs. 16.3 +/- 0.4, P = 0.0012,
      isoflurane vs. control in Cav-1 small interfering RNA vs. scrambled small
      interfering RNA treated cells, respectively). The protective effect of isoflurane
      with various exposure times on apoptosis was enhanced in HT29 cells
      overexpressing Cav-1 (P < 0.001 by two-way ANOVA). Pertussis toxin effectively
      blocked the antiapoptotic effect of isoflurane exhibited by Cav-1 in all cell
      lines. Cav-1 cells had increased glycolysis with isoflurane exposure; however, in
      the presence of tumor necrosis factor-related apoptosis-inducing ligand, this
      increase in glycolysis was maintained in HT29-Cav-1 but not control cells.
      CONCLUSION: Brief isoflurane exposure leads to resistance against apoptosis via a
      Cav-1-dependent mechanism.

PMID- 21862888
TI  - A rural scene by dennis jackson.

PMID- 21862887
TI  - Isoflurane differentially modulates mitochondrial reactive oxygen species
      production via forward versus reverse electron transport flow: implications for
      preconditioning.
AB  - BACKGROUND: Reactive oxygen species (ROS) mediate the effects of anesthetic
      precondition to protect against ischemia and reperfusion injury, but the
      mechanisms of ROS generation remain unclear. In this study, the authors
      investigated if mitochondria-targeted antioxidant (mitotempol) abolishes the
      cardioprotective effects of anesthetic preconditioning. Further, the authors
      investigated the mechanism by which isoflurane alters ROS generation in isolated
      mitochondria and submitochondrial particles. METHODS: Rats were pretreated with
      0.9% saline, 3.0 mg/kg mitotempol in the absence or presence of 30 min exposure
      to isoflurane. Myocardial infarction was induced by left anterior descending
      artery occlusion for 30 min followed by reperfusion for 2 h and infarct size
      measurements. Mitochondrial ROS production was determined
      spectrofluorometrically. The effect of isoflurane on enzymatic activity of
      mitochondrial respiratory complexes was also determined. RESULTS: Isoflurane
      reduced myocardial infarct size (40 +/- 9% = mean +/- SD) compared with control
      experiments (60 +/- 4%). Mitotempol abolished the cardioprotective effects of
      anesthetic preconditioning (60 +/- 9%). Isoflurane enhanced ROS generation in
      submitochondrial particles with nicotinamide adenine dinucleotide (reduced form),
      but not with succinate, as substrate. In intact mitochondria, isoflurane enhanced
      ROS production in the presence of rotenone, antimycin A, or ubiquinone when
      pyruvate and malate were substrates, but isoflurane attenuated ROS production
      when succinate was substrate. Mitochondrial respiratory experiments and electron
      transport chain complex assays revealed that isoflurane inhibited only complex I
      activity. CONCLUSIONS: The results demonstrated that isoflurane produces ROS at
      complex I and III of the respiratory chain via the attenuation of complex I
      activity. The action on complex I decreases unfavorable reverse electron flow and
      ROS release in myocardium during reperfusion.

PMID- 21862889
TI  - No clinical or electrophysiologic evidence of nerve injury after intraneural
      injection during sciatic popliteal block.
AB  - BACKGROUND: Intraneural injection during nerve-stimulator-guided sciatic block at
      the popliteal fossa may be a common occurrence. Although intraneural injections
      have not resulted in clinically detectable neurologic injury in small studies in
      human subjects, intraneural injections result in postinjection inflammation in
      animal models. This study used clinical, imaging, and electrophysiologic measures
      to evaluate the occurrence of any subclinical neurologic injury in patients with
      intraneural injection during sciatic popliteal block. METHODS: Twenty patients
      undergoing popliteal block were enrolled; 17 patients completed the study
      protocol. After tibial nerve response was achieved by nerve stimulation (0.3-0.5
      mA; 2 Hz; 0.1 ms), 20 ml mixture of mepivacaine (1.25%) and radiopaque contrast
      (2 ml) were injected. Location and spread of the injectant were assessed by
      ultrasound measurements of the sciatic nerve area before and after injection, and
      by computed tomography. In addition to clinical neurologic evaluations, serial
      electrophysiologic studies (nerve conduction and late response studies using
      predefined criteria) were performed at baseline and at 1 week and 3 weeks after
      the block for signs of subclinical neurologic dysfunction. RESULTS: Sixteen
      injections (94%, 95% CI: 71-100%) met criteria for an intraneural injection.
      Postinjection nerve area on ultrasound increased by 45% (95% CI: 29-58%), P <
      0.001. Computed tomography demonstrated fascicular separation in 70% (95% CI: 44
      90%), air within the nerve in 29% (95% CI: 10-56%), contrast along bifurcations
      in 65% (95% CI: 38-86%), and concentric contrast layers in 100% (95% CI: 84
      100%). Neither clinical nor electrophysiologic studies detected neurologic
      dysfunction indicating injury to the nerve. CONCLUSIONS: Nerve-stimulator-guided
      sciatic block at the popliteal fossa often results in intraneural injection that
      may not lead to clinical or electrophysiologic nerve injury.

PMID- 21862890
TI  - An american patent for the schimmelbusch mask.

PMID- 21862891
TI  - Retrospective data review and propensity scoring: religion (believing) or science
      (proving) and the appropriate application of statistics.

PMID- 21862892
TI  - Relevance and value of a morphine immunoassay as a diagnostic aid for
      neuromuscular blocking drug-induced anaphylaxis.

PMID- 21862893
TI  - In reply.

PMID- 21862894
TI  - In reply.

PMID- 21862895
TI  - Erythrocyte transfusion: a fair balance.

PMID- 21862896
TI  - Other issues with defibrillators.

PMID- 21862897
TI  - Eye & Contact Lens has an impact factor.

PMID- 21862898
TI  - Intrascleral reverse pocket approach of transconjunctival transscleral sulcus
      fixation of intraocular lens in eyes with ocular trauma.
AB  - PURPOSE: To evaluate the efficacy of a novel technique of intrascleral reverse
      pocket approach of transconjunctival transscleral (TC-TS) sulcus fixation of
      intraocular lens (IOL) implants in posttraumatic eyes. METHOD: A prospective case
      series of 12 patients who had ocular trauma underwent TC-TS fixation of
      intraocular implants (including posterior chamber IOLs, rigid or foldable and
      capsular tension ring) were examined for any intraoperative complications,
      postoperative best-corrected visual acuity (BCVA), status of conjunctiva, and
      other potential complications. RESULTS: Twelve eyes of 12 patients (8 men and 4
      women) with a mean follow-up of 14.5+/-7.25 months were included in the analysis.
      In no case was any intraoperative deroofing of the tunnel or buttonholing of the
      conjunctiva performed. The mean final BCVA (in Snellen Equivalent [SE]) showed
      significant improvement from preoperative levels (0.48+/-0.29 SE vs. 0.65+/-0.19
      SE, respectively; P=0.049). One case showed a single line drop in the BCVA at
      final follow-up. Another case had a dispersed vitreous hemorrhage in the
      immediate postoperative period that cleared in 3 weeks' time. One eye
      demonstrated a clinically detectable IOL tilt, which was corrected by astigmatic
      prescription in the spectacle glass. None of the cases exhibited postoperative
      suture knot erosion or breakage of polypropylene sutures until the last follow
      up. CONCLUSIONS: The technique of intrascleral reverse pocket approach of TC-TS
      fixation is a successful method of sulcus fixation, which can obviate the need
      for conjunctival peritomy, thus helping in salvaging the conjunctiva for any
      future trabeculectomy in posttraumatic eyes predisposed to developing glaucoma.

PMID- 21862899
TI  - Assessment of effects of multipurpose contact lens care solutions on human
      corneal epithelial cells.

PMID- 21862902
TI  - Setting the record straight: response to: Turner JA, Hollingworth W, Comstock B,
      Deyo RA. Comparative effectiveness research and policy: experiences conducting a
      coverage with evidence development study of a therapeutic device.

PMID- 21862903
TI  - A call for rigorous SCS studies.

PMID- 21862904
TI  - System factors affecting long-term care outcomes.

PMID- 21862905
TI  - The effect of Medicaid nursing home reimbursement policy on Medicare hospice use
      in nursing homes.
AB  - OBJECTIVE: To understand how changes in Medicaid nursing home (NH) reimbursement
      policy and rates affect a NH's approach to end-of-life care (ie, its use of
      hospice). METHODS: This longitudinal study merged US NH decedents' (1999 to 2004)
      resident assessment data (MDS) with Part A claims data to determine the
      proportion of a NH's decedents using hospice. Freestanding NHs across the 48
      contiguous US states were included. A NH-level analytic file was merged with NH
      survey (ie, OSCAR) and area resource file data, and with annual data on state
      Medicaid NH rates, case-mix reimbursement policies, and hospice certificate of
      need (CON). NH fixed-effect (within) regression analysis examined the effect of
      changing state policies, controlling for differing time trends in CON and case
      mix states and for facility-level and county-level attributes. Models were
      stratified by urban/rural status. RESULTS: A $10 increase in the Medicaid rate
      resulted in a 0.41% [95% confidence interval (CI): 0.275, 0.553] increase in
      hospice use in urban NHs and a 0.37% decrease (95% CI: -0.676, -0.063) in rural
      NHs not adjacent to urban areas. There was a nonstatistically significant
      increase in rural NHs adjacent to urban areas. Introduction of case-mix
      reimbursement resulted in a 2.14% (95% CI: 1.388, 2.896) increase in hospice use
      in urban NHs, with comparable increases in rural NHs. CONCLUSIONS: This study
      supports and extends previous research by showing changes in Medicaid NH
      reimbursement policies affect a NH's approach to end-of-life care. It also shows
      how policy changes can have differing effects depending on a NH's urban/rural
      status.

PMID- 21862907
TI  - Inpatient rehabilitation outcomes for older adults with nondebility generalized
      weakness.
AB  - OBJECTIVE: This study aimed to compare the functional outcomes and discharge
      locations of older adults admitted to inpatient rehabilitation with debility
      (International Classification of Diseases, 9th Revision, Clinical Modification,
      [ICD-9-CM] code 799.3) with those of patients with a nondebility generalized
      weakness diagnosis (ICD-9-CM codes 728.2, 728.87, and 780.79). DESIGN: This is a
      retrospective cohort study using 2002-2003 information from the Uniform Data
      System for Medical Rehabilitation. Patients were 65 yrs or older admitted to
      inpatient rehabilitation with a primary diagnosis of debility (n = 14,835) and
      nondebility generalized weakness (n = 6,403). Primary outcome measures were
      change in functional status, including efficiency (functional status change
      divided by length of stay in days), and discharge setting. RESULTS: The
      efficiency of the patients with nondebility generalized weakness (1.8 +/- 1.9)
      was statistically greater than that of patients with debility (1.7 +/- 2.1, P =
      0.002), and significantly more patients with nondebility generalized weakness
      were discharged home (70% vs. 68%, P = 0.003). CONCLUSIONS: From a clinical
      standpoint, the functional recovery and rate of discharge to home of inpatient
      rehabilitation patients with nondebility generalized weakness are nearly
      identical to those of patients with debility. Although it would require a policy
      change, we recommend using a single diagnostic code for all of these patients to
      further research in this area of rehabilitation.

PMID- 21862908
TI  - Cervical cord injury after massage.
AB  - We present the case of a 47-yr-old gentleman with cervical cord injury after he
      received massage in the neck area. Magnetic resonance imaging of the cervical
      spine showed a herniation of the nucleus pulposus and compressive myelopathy. The
      patient required surgical intervention and rehabilitation. Despite 6 mos of
      rehabilitation, residual hand dysfunction and minor ambulation problems
      persisted. Although massage has many benefits, this case reminds us that there is
      potential danger in performing neck massage.

PMID- 21862909
TI  - Reliability and concurrent validity of the step quick turn test in older persons
      with a unilateral transtibial amputation.
AB  - OBJECTIVE: This study aimed to investigate the reliability and validity of the
      Step Quick Turn Test in older transtibial amputees. DESIGN: Fifteen male and
      female transtibial amputees repeated the timed "up and go" test and the Step
      Quick Turn Test measures of turn time (TT) and turn sway (TS) each to the
      prosthetic and sound side, approximately 2 wks apart. RESULTS: The intraclass
      correlation coefficients (2,1) for TT and TS were excellent (>= 0.85). Spearman
      rank correlation coefficients between the timed "up and go" test and the TT of
      turning to each side and TS on the prosthetic side were excellent (>= 0.75),
      whereas that for the TS to the sound side was fair to good (0.58). CONCLUSIONS:
      The TT and TS demonstrate an acceptable reliability for individual use in a
      clinical setting with the exception of TT to the prosthetic side. Differences in
      validity between the prosthetic and sound sides were also identified, with TT
      demonstrating excellent validity against the timed "up and go" test for both
      sides, whereas the TS was weaker when evaluated toward the sound side.

PMID- 21862910
TI  - Refractory venous thrombus propagation in the setting of therapeutic
      anticoagulation.

PMID- 21862911
TI  - Digital stereophotogrammetry as a new technique to quantify truncal deformity: a
      pilot study in persons with osteogenesis imperfecta.
AB  - The objective of this pilot study was to determine the usability of
      stereophotogrammetry (SP) as a noninvasive technique for obtaining linear
      measures and anatomical data of the torso in people with osteogenesis imperfecta
      in comparison with clinical observations. Ten participants were recruited from
      subjects enrolled in ongoing institutional review board-approved osteogenesis
      imperfecta protocols at the National Institute of Child Health and Human
      Development. Using a Gulick tape measure, anthropometer, and the SP system
      proprietary software, linear measurements of the torso were taken. In addition,
      the presence or absence of specific torso deformities was documented from both
      clinical observation and evaluation of SP images. Measurements of torso diameter
      and circumference by SP demonstrated strong agreement with the manual
      measurements (intraclass correlation coefficient = 0.995 and 0.964,
      respectively). Substantial and statistically significant agreement was present
      between SP image evaluation and clinical observation for pectus carinatum (kappa
      = 0.52 +/- 0.23) and thoracic scoliosis (kappa = 0.72 +/- 0.12). The kappa values
      between clinical observation and SP evaluations of other torso deformities were
      not significant. The strong correlations and P values determined by this study
      demonstrate the potential value of SP in studying persons with truncal
      deformities. However, the weak agreement between SP and some clinical
      observations suggests that further development of SP image analysis tools is
      required before SP can be used as a standard method of diagnosis or assessment of
      treatment success.

PMID- 21862912
TI  - Determinants of the repeated-bout effect after lengthening contractions.
AB  - OBJECTIVE: Stresses to skeletal muscle often result in injury. A subsequent bout
      of the same activity performed days or even weeks after an initial bout results
      in significantly less damage. The underlying causes of this phenomenon, termed
      the "repeated-bout effect" (RBE), are unclear. This study compared the protective
      effect of two different injury protocols on the ankle dorsiflexors in the rat. We
      hypothesized that the RBE would occur soon after the initial injury and persist
      for several weeks and that the RBE would occur even if the second injury was
      performed under different biomechanical conditions than the first. DESIGN: In
      this controlled laboratory study, the dorsiflexor muscles in the left hind limbs
      of adult male Sprague-Dawley rats (N = 75) were subjected to ten repetitions of
      large-strain lengthening contractions or 150 repetitions of small-strain
      lengthening contractions. RESULTS: Both protocols induced a significant (P <
      0.001) and similar loss of isometric torque (approximately 50%) after the first
      bout of contractions. The RBE occurred as early as 2 days after the injury and
      remained high for 14 days (P < 0.001) but diminished by 28 days and was lost by
      42 days. The small-strain contractions offered a protective effect against a
      subsequent large-strain contraction, but not vice versa. Although the RBE did not
      occur sooner than day 2, the early recovery after a second large-strain injury
      performed 8 hrs after the first was 2-fold greater than after a single injury.
      CONCLUSIONS: The RBE is both rapid in onset and prolonged, and some, but not all,
      injuries can protect against different types of subsequent injury.

PMID- 21862913
TI  - Quantitative assessment of nipple perfusion with near-infrared fluorescence
      imaging.
AB  - Preserving the nipple-areolar complex with a nipple-sparing mastectomy improves
      cosmesis compared with skin-sparing mastectomy. However, complications such as
      necrosis of the nipple-areolar complex significantly affect cosmetic outcome.
      Many factors influence nipple-areolar perfusion, and no consensus currently
      exists on optimal incisional choice. This study evaluates 2 nipple-sparing
      mastectomy incision models using near-infrared fluorescence to assess perfusion
      quantitatively. The periareolar and radial incisions were compared with 2 control
      models in Yorkshire pigs (N = 6). Methylene blue and indocyanine green were
      injected intravenously, and near-infrared fluorescence images were recorded at 3
      time points: before surgery, immediately after (0 hour), and 3 days
      postoperatively. Contrast-to-background ratio was used to assess perfusion. At 72
      hours, radial incisions showed a statistically significantly higher perfusion
      compared with periareolar incisions (P < 0.05). Based on our findings, radial
      incisions for nipple-sparing mastectomy may be preferable due to higher
      perfusion; however, clinical trials are necessary for further assessment.

PMID- 21862914
TI  - Fanconi anemia with concurrent thumb polydactyly and dorsal dimelia: a case
      report with discussion of embryology.
AB  - Fanconi anemia is known to be associated with radial ray deficiency (thumb and
      radius hypoplasia), and its embryological basis remains to be poorly understood.
      We describe a rare case of Fanconi anemia with concurrent thumb polydactyly and
      dorsal dimelia. The embryological basis of limb abnormalities in Fanconi anemia
      patients is thought to be based on the complex interactions between the apical
      ectodermal ridge (where Fanconi anemia genes are expressed) and both the mesoderm
      (where Spalt-like 4 (SALL4) and Sonic hedgehog (SHH) are located and which are
      responsible for radial ray deficiency, thumb polydactyly, and triphalangism) and
      the dorsoventral axis (an error in that axis leads to dorsal dimelia).

PMID- 21862915
TI  - Comparison study of two types of expander-based breast reconstruction: acellular
      dermal matrix-assisted versus total submuscular placement.
AB  - Recent reported complications have called some authors to express concern
      regarding the increased popularity of acellular dermal matrix (ADM)-based breast
      reconstruction, and its role as an alternative to traditional total submuscular
      approaches. To address this issue, we compared tissue expansion properties,
      complication rates, and patient satisfaction for both operative techniques at the
      same institution. A retrospective review was completed on 75 patients and 100
      tissue expander/implant-based breast reconstructions at a single academic
      institution from 2007 to 2010. Of these cases, 31 patients were reconstructed
      with ADM and 44 with a submuscular coverage technique. Total complications
      including seroma, hematoma, infection, skin necrosis, and explantation did not
      significantly differ between groups (n = 13 for ADM vs. 17 for submuscular, P =
      0.814). Consistent with prior reports, ADM-based reconstructions were associated
      with significantly increased intraoperative fill volumes and lower total number
      of sessions to achieve final volume. Submuscular reconstructions required a
      significantly higher tissue expander fill volume. Eight patients in the
      submuscular group required surgical revision of the breast and inframammary fold,
      compared with 4 in the ADM group; however, this difference was not significant.
      Patient satisfaction was equivalent between the 2 groups; however, it was higher
      in patients with bilateral reconstruction and lower among those who had received
      adjuvant radiation therapy. Satisfaction with nipple reconstruction was inversely
      proportional to time elapsed from the procedure to survey conduction. This is the
      first study to perform a head-to-head comparison on the basis of patient
      satisfaction, the results of which may be useful in preoperative planning and
      counseling.

PMID- 21862916
TI  - Current trends in breast reconstruction: survey of American Society of Plastic
      Surgeons 2010.
AB  - BACKGROUND: We conducted a retrospective survey of American Society of Plastic
      Surgeons to ascertain the current trends in breast reconstruction (BR). METHODS:
      Surveys were sent to 2250 active American Society of Plastic Surgeons members by
      e-mail with a cover letter including the link using Survey Monkey for the year
      2010. In all, 489 surveys (a response rate of 21.7%) were returned. Three hundred
      fifty-eight surveys from respondents performing BR in their practices were
      included in the study. The survey included questions on surgeon demographics,
      practice characteristics, BR after mastectomy, number of BR per year, type and
      timing of BR, use of acellular dermal matrix, reconstructive choices in the
      setting of previous irradiation and in patients requiring postmastectomy
      radiation therapy, timing of contralateral breast surgery, fat grafting,
      techniques used for nipple-areola reconstruction, the complications, and
      physician satisfaction and physician reported patient satisfaction. Returned
      responses were tabulated and assessed. RESULTS: After prophylactic mastectomy,
      16% of BRs were performed. In all, 81.2% of plastic surgeons predominantly
      performed immediate BR. In patients requiring postmastectomy radiation therapy,
      81% did not perform immediate BR. Regardless of practice setting and laterality
      of reconstruction, 82.7% of respondents predominantly performed implant-based BR.
      Half of the plastic surgeons performing prosthetic BR used acellular dermal
      matrix. Only 14% of plastic surgeons predominantly performed autologous BR.
      Surgeons in solo, plastic surgery group practices, and multispecialty group
      practices preferred implant-based BR for both unilateral and bilateral cases more
      frequently than those in academic practices (P < 0.05). Overall, plastic surgeons
      in academic settings preferred autologous BR more frequently than those in other
      practice locations (P < 0.05). Of total respondents, 64.8% did not perform
      microsurgical BR at all; 28% reported performing deep inferior epigastric
      perforator flap BR. Pedicled transverse rectus abdominis myocutaneous flap was
      the most often used option for unilateral autologous reconstruction, whereas deep
      inferior epigastric perforator flap was the most commonly used technique for
      bilateral BR. The overall complication rate reported by respondents was 11%.
      CONCLUSION: The survey provides an insight to the current trends in BR practice
      with respect to surgeon and practice setting characteristics. Although not
      necessarily the correct best practices, the survey does demonstrate a likely
      portrayal of what is being practiced in the United States in the area of BR.

PMID- 21862917
TI  - Secondary surgery for functional improvement after hand transplantation.
AB  - Unilateral and bilateral hand transplantations have been performed worldwide with
      good midterm functional results. The role of secondary surgery to improve
      function in the patients with hand transplant has not been uniformly agreed upon.
      A series of 10 secondary procedures were performed in 5 surgeries on 3 patients
      with bilateral upper extremity transplantation. There was 1 incidence of acute
      rejection after 1 procedure. The functional improvement was evaluated
      subjectively by the patients as substantial. Secondary procedures can upgrade
      function after hand transplantation and provide unique opportunities for deep
      tissue biopsies. The proinflammatory stimulus of the surgery can theoretically
      precipitate an acute rejection. The pharmacologic interference of some
      immunosuppressive drugs with wound healing should also be considered.

PMID- 21862918
TI  - Optimizing delivery of breast conservation therapy: a multidisciplinary approach
      to oncoplastic surgery.
AB  - BACKGROUND: For patients with small breasts relative to tumor size and for those
      with tumors in the central or inferior poles, lumpectomy can be aesthetically
      devastating. The field of oncoplastic surgery has developed to offset the
      aesthetic pitfalls of breast conservation. Questions remain regarding oncologic
      safety, potential complications, and patient selection. In this study, we report
      our institutional, multidisciplinary experience with oncoplastic surgery.
      METHODS: A retrospective review was performed including all patients at our
      institution undergoing oncoplastic breast surgery between 2003 and September 2009
      at an academic medical center. Mean follow-up period was 38 months. All patients
      were referred by the institutional multidisciplinary breast team. RESULTS: Forty
      five female patients underwent 46 oncoplastic breast reconstructions. Immediate
      reconstruction was performed in 21 patients, early (within 9 to 73 days of final
      tumor resection) in 18, and delayed (following completion of radiation) in 6.
      Three patients (14%) who underwent immediate oncoplastic reconstruction had
      positive margins on final pathology and proceeded to completion mastectomy. No
      local cancer recurrence was seen. Two patients developed distant metastatic
      disease. Twelve complications occurred in 11 patients; by group, 2 (10%) in
      immediate, 7 (39%) in delayed-immediate group, and 2 (33%) in delayed. Immediate
      oncoplastic reconstruction, performed as a single-stage procedure, inversely
      correlated with complication risk (P = 0.059). No other risk factor correlated
      with complications. CONCLUSIONS: Our review suggests this multidisciplinary
      approach to oncoplastic surgery is safe. Interestingly, women undergoing
      immediate oncoplastic reconstruction trended toward a lower rate of
      complications. The benefit of immediate reconstruction must be balanced by risk
      of positive tumor margin and subsequent necessity for completion mastectomy. This
      risk-benefit balance may be best delivered by a multidisciplinary team focused on
      all aspects of breast cancer care.

PMID- 21862919
TI  - Columella reconstruction using a free flap from the first web space of the foot.
AB  - Nasal columella defects can result in significant cosmetic and functional
      deformities. If a local flap transfer cannot be performed, columella
      reconstruction becomes a significant challenge for the surgeon. The columella of
      a healthy 30-year-old woman whose nose was scarred and contracted because of
      cocaine abuse, was successfully reconstructed by transferring a microvascular
      free flap from the first web space of the foot. The reconstructed columella had a
      satisfactory contour and a good texture, although there was slight, albeit
      unproblematic, color mismatching.

PMID- 21862920
TI  - Initial experience with the use of porcine acellular dermal matrix (Strattice)
      for abdominal wall reinforcement after transverse rectus abdominis myocutaneous
      flap breast reconstruction.
AB  - Reestablishing anterior rectus fascial integrity remains a clinical challenge
      after transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction.
      The main concerns include herniation and bulging due to abdominal weakness. Mesh
      assisted closure of the fascial defect has improved bulging and herniation rates
      but infection, extrusion, and encapsulation are serious concerns with mesh use.
      Biologic tissue matrices may overcome some of these mesh-related complications.
      The initial experience of using Strattice for fascial closure after TRAM flap
      procedure is described in this article. Strattice was in-lain and sutured between
      the anterior and posterior layers of the rectus fascia, at the rectus muscle
      donor site. The abdominal wall was closed with progressive tension sutures.
      Postoperative complications at the donor site were assessed. A total of 16
      unilateral and 9 bilateral reconstructions were performed in 25 patients. Length
      of hospital stay was 2 to 3 days which is shorter than with mesh repair
      (typically 4-5 days). During a mean follow-up period of 14.0 months,
      complications occurred in 7 patients (28%): seroma formation (2), minor skin
      separation (2), superficial skin infection (2), and superficial wound dehiscence
      (1). Complications were not directly related to Strattice and all, except one
      (superficial skin infection), were resolved without surgical intervention. In all
      patients, routine abdominal functions were restored 4 months postoperatively.
      Strattice is a safe, alternative option to synthetic mesh for fascial repair
      following TRAM flap breast reconstruction. When used in conjunction with
      progressive tension suture closure of the abdominal wall, dynamic reconstruction
      of the abdominal wall with resumption of abdominal function is possible with
      Strattice.

PMID- 21862921
TI  - Extracorporeal septoplasty: functional results of a modified technique.
AB  - BACKGROUND: Severe nasoseptal deviations still represent challenging situations
      for plastic surgeons. Septal surgery plays a central role in the management of
      complex cosmetic and functional problems, and should be considered as a basic
      procedure in nasal surgery. The classic septoplasty approach seems to be
      unsuitable for severe septal deviations. Other authors have found the standard
      extracorporeal septoplasty approach more reliable for a correct functional and
      cosmetic surgery. However, a drawback of this technique is the destabilization of
      the keystone area. In an effort to minimize the risk of destabilization, we have
      modified the classic technique with a more conservative approach that spares the
      dorsal cartilage and a portion of the caudal septum. METHODS: This study included
      153 patients who underwent primary rhinoplasty from January 2006 to June 2009.
      The purpose was to evaluate the effectiveness of this technique in terms of
      objective (Active Anterior Rhinomanometry) and subjective (Nasal Obstruction
      Symptom Evaluation [NOSE] scale) improvements of the respiratory function and in
      terms of postoperative complications. There was a significant improvement in mean
      NOSE score at 3 and 6 months postoperatively. Rhinomanometrical assessment showed
      a significant increase of the nasal inspiratory flow at 3 and 6 months after
      surgery. No complications were reported. CONCLUSIONS: The results obtained with
      NOSE score and with rhinomanometrical assessment revealed that this technique
      increases patient's quality of life and nasal respiratory function, respectively.
      Furthermore, our approach avoids the most important complication of classic
      extracorporeal septoplasty, thus preserving a structured support of the nasal
      archway.

PMID- 21862922
TI  - The application of bilateral lip mucosa flaps in repairing upper vermilion
      defects.
AB  - BACKGROUND: The lip is a primary aesthetic feature of the human face. Repair of
      vermilion defects represents a unique challenge to the reconstructive surgeon.
      The methods of repair are various and have both advantages and disadvantages.
      Bilateral lip mucosa flaps were applied to the repair of upper vermilion defects,
      and the effects were observed and reported in this article. METHODS: The
      bilateral lip mucosa flaps were designed. Two reverse triangular flaps were
      designed on both sides of the upper vermilion defect. These 2 flaps have the
      common pedicle in the vermilion depression site. Alternatively, a "lambda"
      incision may be used in the wet vermilion. Then, the mucosa flaps were raised,
      and the dissection was performed between the orbicularis oris muscles and oral
      mucosa glands. Next, the bilateral mucosa flaps were rotated down 90 degrees  and
      inserted into the "lambda" incision to increase the tissue volume of the middle
      upper lip and deepen the labiogingival sulcus. The common pedicle of the mucosa
      flaps was formed to the vermilion tubercle, and the incisions were sutured layer
      by layer. RESULTS: From 2005 to 2010, the bilateral mucosa flaps procedures were
      performed on 30 secondary cleft lip patients (bilateral, n=22; unilateral, n=8).
      Lateral projection measurements of the reconstructive vermilion tubercle showed a
      mean increase of 149%. Satisfactory results were obtained, both cosmetically and
      functionally, in all 30 patients. There were minimal perioperative complications.
      The postoperative scars are not remarkable at all. CONCLUSIONS: The technique is
      relatively simple. The bilateral lip mucosa flaps provided a versatile and
      reliable option for the correction of vermilion defects from secondary cleft lip
      deformities.

PMID- 21862923
TI  - Perioperative stroke in noncardiac, nonneurosurgical surgery.
AB  - Perioperative stroke after noncardiac, nonneurosurgical procedures is more common
      than generally acknowledged. It is reported to have an incidence of 0.05-7% of
      patients. Most are thrombotic in origin and are noted after discharge from the
      postanesthetic care unit. Common predisposing factors include age, a previous
      stroke, atrial fibrillation, and vascular and metabolic diseases. The mortality
      is more than two times greater than in strokes occurring outside the hospital.
      Delayed diagnosis and a synergistic interaction between the inflammatory changes
      normally associated with stroke, and those normally occurring after surgery, may
      explain this increase. Intraoperative hypotension is an infrequent direct cause
      of stroke. Hypotension will augment the injury produced by embolism or other
      causes, and this may be especially important in the postoperative period, during
      which monitoring is not nearly as attentive as in the operating room. Increased
      awareness and management of predisposing risk factors with early detection should
      result in improved outcomes.

PMID- 21862924
TI  - Chronic pain after femoral hernia repair: a cross-sectional study.
AB  - OBJECTIVE: To explore the prevalence of and to identify possible risk factors for
      chronic pain after surgery for femoral hernia. BACKGROUND: Chronic pain has
      become a very important outcome in quality assessment of inguinal hernia surgery.
      There are no studies on the risk for chronic pain after femoral hernia surgery.
      METHODS: The Inguinal Pain Questionnaire was sent to 1967 patients who had had a
      repair for primary unilateral femoral hernia between January 1, 1997 and December
      31, 2006. A follow-up period of at least 18 months was chosen. Answers from 1461
      patients were matched with data recorded in the Swedish Hernia Register and
      analyzed. RESULTS: Some degree of pain during the previous week was reported by
      24.2% (354) of patients. Pain interfered with daily activities in 5.5% (81) of
      patients. Emergency surgery (OR = 0.54; 95% CI = 0.40-0.74) and longer time since
      surgery (OR = 0.93; 95% CI = 0.89-0.98 for each year added) were associated with
      lower risk for chronic postoperative pain, whereas a high level of preoperative
      pain was associated with a higher risk for chronic pain (OR = 1.17; 95% CI = 1.10
      1.25). Surgical technique was not found to influence the risk for chronic pain in
      multivariate logistic regression analysis. CONCLUSIONS: Chronic postoperative
      pain is as important a complication after femoral hernia surgery as it is after
      inguinal hernia surgery. In contrast to inguinal hernia surgery, no risk factor
      related to surgical technique was found. Further investigations into the role of
      preoperative pain are necessary.

PMID- 21862925
TI  - Superior preservation of DCD livers with continuous normothermic perfusion.
AB  - OBJECTIVE: Unexpected donation after cardiac death (DCD) donors suffer cardiac
      arrest suddenly and are maintained with normothermic extracorporeal membrane
      oxygenation (NECMO) while consent for donation is obtained. The objective of this
      study was to determine whether ex vivo normothermic machine perfusion (NMP)
      improves upon the benefits of NECMO in a large-animal model of unexpected DCD
      liver transplant. METHODS: Donor pigs underwent 90-minute cardiac arrest and were
      divided in to 3 groups. In the first, livers were preserved immediately with cold
      storage (CS, n = 6). In the other 2 groups, donors underwent 60-minute NECMO
      followed by CS (NECMO+CS, n = 6) or NMP (NECMO+NMP, n = 6). After 4-hour
      preservation, livers were transplanted into recipient pigs. RESULTS: Five-day
      survival was 0 in CS, 83% in NECMO+CS, and 100% in NECMO+NMP. After reperfusion,
      injury, and inflammatory markers rose significantly among CS grafts, all of which
      developed primary nonfunction. Sixty minutes of NECMO, however, resulted in only
      1 death, whereas NECMO followed by NMP led to no deaths and significant
      improvements in injury, inflammation, and synthetic function in comparison to
      NECMO and CS. CONCLUSION: Although 60 minutes recuperative NECMO is better than
      CS alone, NMP improves further on NECMO and may have a role in preserving DCD
      livers in the clinical setting.

PMID- 21862926
TI  - The role of Helicobacter pylori infection in the web of gastric cancer causation.
AB  - The decline in gastric cancer mortality is a major achievement in cancer control.
      It has been attributed to a set of factors related to the improvement of the
      populations' living conditions, namely the increase in the consumption of fruit
      and vegetables and the decrease in salt intake, and therefore labelled as an
      'unplanned triumph'. In the last decades, however, we witnessed the gradual
      acceptance of Helicobacter pylori infection as the most important environmental
      factor contributing to the occurrence of gastric cancer. The potential for
      further reducing the burden of cancer by acting on a single modifiable exposure,
      that is, preventing or treating infection, and the extent to which it may be
      achieved, requires an in-depth knowledge of the contribution of H. pylori
      infection to the causal mechanisms leading to cancer. We propose a conceptual
      framework for the interpretation of the role of H. pylori infection in the web of
      gastric cancer causation, taking into account the nosological heterogeneity of
      gastric cancer, the induction period for the action of H. pylori infection and
      its potential role as a necessary component cause.

PMID- 21862927
TI  - Experience of step-wise protocol using noninvasive positive pressure ventilation
      for treating cardiogenic pulmonary edema.
AB  - Initiating and weaning procedure of noninvasive positive pressure ventilation
      (NIPPV) on acute cardiogenic pulmonary edema (ACPE) has been determined
      empirically, and the total time of its use has been sometimes prolonged
      unnecessarily. A simple protocol for its use may facilitate initiation and avoids
      prolongation of the NIPPV treatment. We designed a step-wise protocol for NIPPV
      use and retrospectively examined the clinical outcome of our protocol for
      initiation and weaning of NIPPV in 45 patients with ACPE. Almost all patients
      recovered from respiratory distress successfully. There was no intubation nor
      complication related to NIPPV. In most of the cases, maximal-end expiratory
      pressure was less than 7-cm H2O. The mean duration of NIPPV was 19.5+/-28.0 h and
      the median duration was 8.0 h (interquartile range=14.0 h). This simple step-wise
      NIPPV protocol for ACPE can facilitate quick and safe initiation and termination
      of the treatment.

PMID- 21862928
TI  - Epidemiology of assault and self-harm injuries treated in a large Romanian
      Emergency Department.
AB  - OBJECTIVES: Intentional injury, including interpersonal violence and self-harm,
      is one of the world's leading causes of preventable injury. In Europe alone,
      nearly 1.5 million individuals receive medical treatment each year for a violence
      related injury. We examined violent injuries treated in the largest Emergency
      Department (ED) in Tirgu Mures County, Romania, with a catchment area of
      approximately 580 000 residents to describe the epidemiology of assault and self
      harm injuries. METHODS: Data were collected as part of the European Injury
      Database project, from a sample of patients who presented with a violence-related
      injury and received care from the ED of the Mures County Emergency Hospital,
      Romania. The data were collected for 9 months by two trained emergency
      physicians. Information about individual demographics; mechanism, nature, place,
      and activity of injury; injury types, and body regions affected; and discharge
      state were compared for assault and self-harm injuries. RESULTS: Of the 380
      patients treated for violence-related injuries, 88.7% were for assault and 11.3%
      were for self-harm. For both types of injuries, the majority of patients were
      between the ages of 15 and 44. Assaults frequently occurred in the home, on
      streets and highways, or in public places; and men (80.4%) were far more likely
      than women (19.6%) to be treated for this type of injury; a slightly higher
      proportion of men (55.8%) than women (44.2%) were treated for self-harm, most of
      which occurred in homes. DISCUSSION: Of all injuries treated in the Tirgu Mures
      ED, one out of five was violence related. One out of 10 patients that suffered an
      injury as a consequence of a violent event and treated in the ED required
      admission to a hospital for further medical care, leading to a significant health
      care burden. These data suggest that prevention strategies should focus on young
      adults, and particularly men. Interventions that focus on detection and treatment
      of psychological illness, reduction of alcohol use and associated aggression, and
      family and intimate partner violence are suggested as priorities.

PMID- 21862929
TI  - Are we prepared for a growing population? Morbid obesity and its implications in
      Irish emergency departments.
AB  - Two percent of the Irish population is morbidly obese with this figure expected
      to rise significantly. This survey aimed to establish the present logistical
      capacity of Irish emergency departments (EDs) to adequately cater for the
      bariatric patients. A telephone survey was carried out of 37 health service
      executive EDs over a 5-day period in October 2008. Questions were posed to the
      departmental lead nurse regarding facilities (Supplemental digital content 1). No
      ED had adequate facilities. Two of 37 units questioned had on-site hoists
      designed to lift patients of more than 170 kg. Four departments had rapid access
      to mattresses within the hospital and three of these four had access to beds and
      trolleys for weighing patients. Two percent of the Irish population is morbidly
      obese with this figure expected to rise significantly to more than 150 kg. One
      department had access to commodes, chairs, wheelchairs and trolleys from
      inpatient services. All departments had extra-wide blood pressure cuffs and 12
      had a difficult airways trolley. Necessary infrastructure and equipment for
      bariatric patients is deficient in the majority of Irish EDs.

PMID- 21862930
TI  - Reprocessing practice in digestive endoscopy units of district hospitals: 
      results of a Portuguese National Survey.
AB  - BACKGROUND AND AIM: An inadequate disinfection of endoscopes and associated
      accessories can result in the transmission of infections to patients. The aim of
      this study was to access reprocessing practice in the endoscopy units of
      Portuguese district general hospitals. METHODS: An anonymous questionnaire on
      cleaning and disinfection methods was sent to all endoscopy units of Portuguese
      district general hospitals. RESULTS: A total of 25 units responded (93%). All
      endoscopy units performed manual cleaning (including brushing of accessible
      channels) before disinfection. Automated endoscope reprocessing machines were
      available in all units. Manual disinfection was performed in only one unit. In
      48% of the surveyed units, endoscopes were systematically disinfected before each
      session, whereas in 16% this was performed only occasionally. The most commonly
      used disinfectant was peracetic acid (32%). Disposable papillotomes, biopsy
      forceps, and polipectomy snares were used in nine (36%), six (24%), and 14 (56%)
      units, respectively. Disposable papillotomes, forceps, and snares were reused in
      three (12%), two (8%), and three (12%) units, respectively, always after
      sterilization. Most units did not perform regular evaluation of reprocessing
      staff competence (60%), regular microbiological inspection (56%), or registry of
      reprocessing (56%). CONCLUSION: The data collected suggest that there is a good
      compliance with standard guidelines. Nevertheless, there is still room for
      improvement mainly in quality assurance.

PMID- 21862931
TI  - Cerebral perfusion pressure below 60 mm Hg is common in the intraoperative
      setting.
AB  - BACKGROUND: Maintaining adequate cerebral perfusion pressure (CPP) is of clinical
      concern in patients with neurological injury. Although there are extensive data
      on CPP in the ICU setting, there has been little quantitative study of CPP in the
      intraoperative setting. METHODS: We retrospectively analyzed the electronic
      intraoperative records of neurosurgical and trauma patients with concurrent
      intracranial and arterial pressure monitoring devices in continuous use for >=45
      minutes to calculate CPP (=mean arterial pressure-intracranial pressure). We
      assessed the total minutes and frequency of 5-minute epochs, during which the
      median CPP was <60 mm Hg, and the associated risk factors. RESULTS: A total of
      155 trauma and neurosurgical patients were studied. In the neurosurgery cohort
      (n=88), 74% had at least one 5-minute epoch during which the median CPP was <60
      mm Hg and the median total minutes of CPP<60 mm Hg was 39 [interquartile range
      (67), length of surgery 274 (300) min]. In the trauma cohort (n=67), 82% had at
      least one 5-minute epoch of <60 mm Hg, and the median total minutes CPP of <60 mm
      Hg was 35 [(59), length of surgery 159 (160) min]. For the entire cohort (n=155),
      patients with CPP<60 mm Hg were found to have higher intracranial pressure
      compared with patients with CPP>=60 mm Hg (P<0.001). Unlike the neurosurgical
      cohort, trauma patients with CPP<60 mm Hg had a greater frequency of episodes of
      mean arterial pressure <70 mm Hg (P=0.001). CONCLUSIONS: CPP<60 mm Hg is common
      in the intraoperative setting of a tertiary medical center in 2 different
      surgical populations with intracranial pathology. Prospective studies of
      intraoperative CPP and neurological outcomes are warranted.

PMID- 21862932
TI  - Cerebrospinal fluid tenascin-C in cerebral vasospasm after aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND: Tenascin-C (TNC) has been reported to be a useful biomarker for the
      activity of inflammatory diseases. This study investigated the association
      between TNC levels in the cerebrospinal fluid (CSF) and symptomatic vasospasm
      after aneurysmal subarachnoid hemorrhage (SAH), and the prognostic value of TNC
      levels. METHODS: TNC levels were measured in CSF in 33 consecutive patients
      diagnosed with aneurysmal SAH of Fisher computed tomography group III and were
      compared between those with and without subsequent cerebral vasospasm. Factors
      influencing symptomatic vasospasm were determined using multivariate logistic
      regression analyses. The receiver-operating characteristic curve technique was
      used to assess specificity and sensitivity in the prediction of symptomatic
      vasospasm. RESULTS: The CSF TNC levels peaked immediately after SAH and were
      significantly higher in patients who subsequently developed symptomatic vasospasm
      than in those who did not. On multivariate analyses, higher TNC levels in the CSF
      (odds ratio, 1.059; 95% confidence interval, 1.023-1.096; P<0.001) and World
      Federation of Neurosurgical Societies grades IV to V on admission (odds ratio,
      3.238; 95% confidence interval, 1.033-10.152; P<0.05) significantly predicted
      symptomatic vasospasm. To predict the onset of symptomatic vasospasm, 16.2 ng/mL
      was considered as an appropriate cut-off value for CSF TNC on days 1 through 6,
      giving a sensitivity of 81.0% and a specificity of 79.5% (negative and positive
      predictive values: 82.3% and 76.7%, respectively). CONCLUSIONS: TNC in the CSF
      may be a useful biomarker for predicting subsequent development of cerebral
      vasospasm.

PMID- 21862933
TI  - Toxocara canis myelitis: clinical features, magnetic resonance imaging (MRI)
      findings, and treatment outcome in 17 patients.
AB  - Toxocara myelitis is a rare disease. Few cases have been reported in the
      literature. Patients present with myelopathy, occasional eosinophilia in blood
      and cerebrospinal fluid (CSF), with abnormal signals on magnetic resonance
      imaging (MRI). In the current study we report 17 cases of isolated Toxocara
      myelitis from a single tertiary referral center in Lebanon, with description of
      the clinical presentation, laboratory data, MRI findings, and response to
      antihelminthic treatment. Clinical and laboratory data were collected for 17
      patients who presented with evidence of spinal cord disease. The clinical
      presentation included sensory, motor, and autonomic dysfunction, predominantly in
      the lower extremities. Patients exhibited a subacute or chronic course; this was
      either slowly progressive or remitting-relapsing with mild to moderate
      disability. The patients underwent extensive blood and CSF workup as well as MRI
      of the spinal cord and brain. Only 2 patients had a high eosinophil count in the
      CSF, although blood eosinophilia was seen in 6 patients. All patients tested
      positive for Toxocara canis antibodies in the blood and CSF. MRI of the spinal
      cord revealed a single characteristic lesion in the spinal cord with fusiform
      enlargement that was isointense on T1-weighted images and hyperintense on T2
      weighted images. Nodular enhancement was seen after gadolinium injection.
      Treatment with albendazole, with or without steroids, resulted in marked
      neurologic improvement and normalization of the MRI in all patients.The finding
      of a single inflammatory MRI lesion in the spinal cord with positive Toxocara
      canis serology in the blood and CSF in cases of subacute or chronic myelitis
      suggests the diagnosis of Toxocara myelitis, irrespective of the presence of
      eosinophilia. Antihelminthic treatment is associated with a good outcome.

PMID- 21862934
TI  - Anti-glomerular basement membrane disease: outcomes of different therapeutic
      regimens in a large single-center Chinese cohort study.
AB  - Anti-glomerular basement membrane (GBM) disease usually presents with rapidly
      progressive glomerulonephritis accompanied by pulmonary hemorrhage. The low
      incidence and fulminant course of disease preclude a large randomized controlled
      study to define the benefits of any given therapy. We conducted a retrospective
      survey of 221 consecutive patients seen from 1998 to 2008 in our hospital, and
      report here the patient and renal survival and the risk factors affecting the
      outcomes. Considering the similar clinical features of the patients, we could
      compare the effects of 3 different treatment regimens: 1) combination therapy of
      plasmapheresis and immunosuppression, 2) steroids and cytotoxic agents, and 3)
      steroids alone.The patient and renal survival rates were 72.7% and 25.0%,
      respectively, at 1 year after disease presentation. The serum level of anti-GBM
      antibodies (increased by 20 U/mL; hazard ratio [HR], 1.16; p = 0.009) and the
      presentation of positive antineutrophil cytoplasmic antibodies (ANCA) (HR, 2.18;
      p = 0.028) were independent predictors for patient death. The serum creatinine at
      presentation (doubling from 1.5 mg/dL; HR, 2.07; p < 0.001) was an independent
      predictor for renal failure.The combination therapy of plasmapheresis plus
      corticosteroids and cyclophosphamide had an overall beneficial effect on both
      patient survival (HR for patient mortality, 0.31; p = 0.001) and renal survival
      (HR for renal failure, 0.60; p = 0.032), particularly patient survival for those
      with Goodpasture syndrome (HR for patient mortality, 0.29; p = 0.004) and renal
      survival for those with anti-GBM nephritis with initial serum creatinine over 6.8
      mg/dL (HR for renal failure, 0.52; p = 0.014). The treatment with corticosteroids
      plus cyclophosphamide was found not to improve the renal outcome of disease (p =
      0.73). In conclusion, the combination therapy was preferred for patients with
      anti-GBM disease, especially those with pulmonary hemorrhage or severe renal
      damage. Early diagnosis was crucial to improving outcomes.

PMID- 21862935
TI  - Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream
      infection: secular trends over 19 years at a university hospital.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is
      a cause of concern in health systems all over the world, due to the high
      incidence rates and the associated undesirable outcomes. In our tertiary 900-bed
      university hospital, all episodes of MRSA-BSI have been prospectively followed up
      since the identification of the first episode in 1990. We conducted the current
      study to report changes in the epidemiology of MRSA-BSI over the 19-year period
      between 1990 and 2008, comparing 4 periods (1990-1994, 1995-1999, 2000-2004, and
      2005-2008). Overall, 524 patients developed MRSA-BSI. Cumulative incidence was
      10.0 episodes/100,000 patient days (range, 1.3-17.4). Although no trend in the
      incidence rate was observed between the 4 consecutive periods, significant upward
      trends in patient age and comorbidities, health care acquisition, and non
      intravascular catheter source were all identified (p < 0.05). While the Iberian
      clone (ST247/SCCmecI) was dominant during the first and second periods, almost
      all the strains isolated in the subsequent periods belonged to Clonal Complex 5
      (ST125/SCCmecIV and ST228/SCCmecI). A significant downward trend in vancomycin
      geometric minimum inhibitory concentration (MIC) was also observed from 2.04 mg/L
      to 0.88 mg/L, coinciding with the clonal replacement and the reduction in the
      hospital vancomycin prescription. Therefore, no MRSA vancomycin MIC creep was
      observed since higher MICs were associated with strains belonging to the Iberian
      clone. Glycopeptides were the most frequently used antibiotics for MRSA-BSI
      during all 4 periods. No differences in MRSA-BSI outcomes were found, and the
      mortality rate at 30 days was close to 29% in each of the 4 periods. In
      conclusion, we identified significant changes in demographic and clinical
      characteristics and in the molecular epidemiology of MRSA-BSI during the study
      period, but found no significant trends in cumulative incidence or in overall
      mortality rate.

PMID- 21862936
TI  - Pneumonia complicating pandemic (H1N1) 2009: risk factors, clinical features, and
      outcomes.
AB  - We performed an observational analysis of a prospective cohort of adults
      hospitalized for pandemic (H1N1) 2009 at 13 Spanish hospitals, from June to
      November 2009, to determine the risk factors, clinical features, and outcomes of
      pneumonia. Of 585 patients requiring hospitalization, chest radiography was
      obtained in 542. A total of 234 (43.1%) patients had pneumonia, of whom 210
      underwent bacterial microbiologic studies. Of these patients, 174 (82.8%) had
      primary viral pneumonia and 36 (17.2%) had concomitant/secondary bacterial
      pneumonia. Bilateral pneumonia occurred in 48.3% of patients. Streptococcus
      pneumoniae was the most frequent pathogen among patients with bacterial pneumonia
      (26 of 36 patients). None of them had received pneumococcal vaccine. Compared
      with patients without pneumonia, those with pneumonia more frequently had shock
      during hospitalization (9.8% vs. 1%; p < 0.001), required intensive care unit
      admission (22.6% vs. 5.8%; p < 0.001), underwent mechanical ventilation (17.9%
      vs. 3.2%; p < 0.001), and had longer length of hospital stay (median, 7 d vs. 5
      d; p < 0.001). In-hospital mortality was higher in patients with pneumonia than
      in the others (5.2% vs. 0%; p < 0.001). Absence of comorbid conditions (odds
      ratio [OR], 2.07; 95% confidence interval [CI], 1.32-3.24) was found to be an
      independent risk factor for pneumonia, whereas early (<= 48 h) oseltamivir
      therapy (OR, 0.29; 95% CI, 0.19-0.46) was a protective factor. In conclusion,
      pneumonia is a frequent complication among adults hospitalized for pandemic
      (H1N1) 2009 and causes significant morbidity. Mortality in pandemic (H1N1) 2009
      is low, but occurs mainly in patients with pneumonia. Early oseltamivir therapy
      is a protective factor for this complication.

PMID- 21862938
TI  - Effects of NR2A and NR2B-containing N-methyl-D-aspartate receptors on neuronal
      firing properties.
AB  - The N-methyl-D-aspartate receptors (NMDARs) play a key role in synaptic
      plasticity, but it remains unclear whether the intrinsic-firing properties,
      another major determinant of the functional output of neurons, are regulated by
      activation of NMDARs. Here, we examine the effects of NMDAR activation on the
      intrinsic-firing properties of medium spiny neurons in nucleus accumbens in
      vitro. NMDAR activation by bath application of NMDA increased both the intrinsic
      excitability and the spike adaptation of these neurons. Furthermore, selective
      activation of NR2A-containing NMDARs mediated the enhancement of spike
      adaptation, whereas selective activation of NR2B-containing NMDARs increased the
      intrinsic excitability, suggesting that NR2A-containing and NR2B-containing
      NMDARs play different roles in mediating the intrinsic-firing properties of
      neurons.

PMID- 21862937
TI  - Panton Valentine Leukocidin exotoxin has no effect on the outcome of cancer
      patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.
AB  - The presence of Panton-Valentine leukocidin (PVL) gene in methicillin-resistant
      Staphylococcus aureus (MRSA) infections has been associated with high severity
      and mortality rates. In this study we evaluated the effect of PVL on outcome in
      cancer patients with MRSA infections.We retrospectively reviewed the records of
      173 cancer patients diagnosed with MRSA pneumonia (n = 47), skin and soft tissue
      infections (n = 77), and bacteremia (n = 49) between September 2003 and September
      2007 at M. D. Anderson Cancer Center. We obtained demographic and clinical data
      and tested isolates for the presence of PVL. The data were compared between
      patients with PVL (+) and those with PVL (-) strains. Statistical methods for
      comparison included Cochran-Mantel-Haenszel tests, 2-way nonparametric analysis
      of variance, chi-square or Fisher exact tests, and Wilcoxon rank sum tests. All
      tests were 2-sided with a significance level of 0.05.Seventy patients with PVL
      (+) strains and 103 patients with PVL (-) strains were included in our study.
      Fewer PVL (+) patients had pneumonia than did PVL (-) patients (14% vs. 36%, p =
      0.002). PVL (-) patients were more likely to have concomitant infections (35% vs.
      17%, p = 0.012). The 2 groups were similar in terms of fever, sepsis, vasopressor
      use, mechanical ventilation, antibiotics response, infection relapse, death, and
      death due to MRSA. In a skin and soft tissue subset analysis, PVL (+) patients
      were more likely to have solid tumors (73% vs. 47%, p = 0.02) and less likely to
      have fever (20% vs. 44%, p = 0.02) and sepsis (12% vs. 36%, p = 0.013). There
      were no differences in outcome between patients with pneumonia and bacteremia;
      however, most patients with pneumonia were PVL (-) (79% vs. 21%). Among the 73
      patients who received vancomycin and the 20 who received linezolid, there was no
      difference in response to treatment, regardless of PVL status or neutropenia. In
      conclusion, the presence of the PVL gene had no negative effect on cancer
      patients with health care-associated MRSA.

PMID- 21862939
TI  - Ischemia-induced neural stem/progenitor cells express pyramidal cell markers.
AB  - Adult brain-derived neural stem cells have acquired a lot of interest as an
      endurable neuronal cell source that can be used for central nervous system repair
      in a wide range of neurological disorders such as ischemic stroke. Recently, we
      identified injury-induced neural stem/progenitor cells in the poststroke murine
      cerebral cortex. In this study, we show that, after differentiation in vitro,
      injury-induced neural stem/progenitor cells express pyramidal cell markers Emx1
      and CaMKIIalpha, as well as mature neuron markers MAP2 and Tuj1. 5-bromo-2
      deoxyuridinine-positive neurons in the peristroke cortex also express such
      pyramidal markers. The presence of newly regenerated pyramidal neurons in the
      poststroke brain might provide a noninvasive therapeutic strategy for stroke
      treatment with functional recovery.

PMID- 21862940
TI  - Protein kinase B is involved in Nogo-66 inhibiting neurite outgrowth in PC12
      cells.
AB  - Nogo-A, a member of the reticulon family, is one of the most important myelin
      associated inhibitors for axonal growth, regeneration, and plasticity in the
      central nervous system. RhoA has been targeted pharmacologically to promote
      neurite outgrowth and functional recovery in the brain and spinal cord. However,
      the underlying mechanism of the inhibition of neurite outgrowth by Nogo-A has not
      yet been fully defined. Protein kinase B (PKB, also known as Akt) is a protein
      serine/threonine kinase that plays a key role in intracellular signaling and
      cellular homeostasis. This study reports the role of PKB signaling on Nogo-A
      treated PC12 neuronal cells. An inhibitory fragment of Nogo-A (Nogo-66) activated
      RhoA and reduced the phosphorylation of PKB at Ser473 in a time-dependent manner.
      In contrast, pretreatment with Y27632, a specific inhibitor of Rho-A, resulted in
      an increase of the phosphorylation of PKB. Nogo-66 also inhibited the neurite
      outgrowth of PC12 cells, whereas pretreatment with LY294002, a specific inhibitor
      of PKB, ameliorated the neurite outgrowth. These data suggest that PKB is
      involved in the inhibition of neurite outgrowth by Nogo-A in PC12 cells.

PMID- 21862941
TI  - Effectiveness of quantitative MAA SPECT/CT for the definition of vascularized
      hepatic volume and dosimetric approach:  phantom validation and clinical
      preliminary results in patients with complex hepatic vascularization treated with
      yttrium-90-labeled microspheres.
AB  - The goal of this study was to assess the use of quantitative single-photon
      emission computed tomography/computed tomography (SPECT/CT) analysis for
      vascularized volume measurements in the use of the yttrium-90-radiolabeled
      microspheres (TheraSphere). A phantom study was conducted for the validation of
      SPECT/CT volume measurement. SPECT/CT quantitative analysis was used for the
      measurement of the volume of distribution of the albumin macroaggregates (MAA;
      i.e., the vascularized volume) in the liver and the tumor, and the total activity
      contained in the liver and the tumor in four consecutive patients presenting with
      a complex liver vascularization referred for a treatment with TheraSphere.
      SPECT/CT volume measurement proved to be accurate (mean error <7%) and
      reproducible (interobserver concordance 0.99). For eight treatments, in cases of
      complex hepatic vascularization, the hepatic volumes based on angiography and CT
      led to a relative overestimation or underestimation of the vascularized hepatic
      volume by 43.2 +/- 32.7% (5-87%) compared with SPECT/CT analyses. The
      vascularized liver volume taken into account calculated from SPECT/CT data,
      instead of angiography and CT data, results in modifying the activity injected
      for three treatments of eight. Moreover, quantitative analysis of SPECT/CT allows
      us to calculate the absorbed dose in the tumor and in the healthy liver, leading
      to doubling of the injected activity for one treatment of eight. MAA SPECT/CT is
      accurate for volume measurements. It provides a valuable contribution to the
      therapeutic planning of patients presenting with complex hepatic vascularization,
      in particular for calculating the vascularized liver volume, the activity to be
      injected and the absorbed doses. Studies should be conducted to assess the role
      of quantitative MAA/SPECT CT in therapeutic planning.

PMID- 21862942
TI  - Selective approach to radionuclide-guided sentinel lymph node biopsy in high-risk
      ductal carcinoma in situ of the breast.
AB  - PURPOSE: Ductal carcinoma in situ (DCIS) currently represents approximately 15
      25% of all breast cancers detected. Although inherently a noninvasive disease,
      occult invasive disease can be found at definitive histology. The role of
      sentinel lymph node (SLN) biopsy in DCIS is still unclear. The aim of this study
      was to evaluate the clinical usefulness of SLN biopsy and the incidence of SLN
      metastases in selected patients with high-risk DCIS, who are at highest risk for
      being upstaged to invasive carcinoma. MATERIALS AND METHODS: Twenty-three high
      risk patients with DCIS proven on core biopsy (mean age, 50 years; median age, 48
      years; age range, 37-78 years) were included in the study. SLN scintigraphy was
      performed 2-4 h before surgery by injecting Tc-99m-labeled nanocolloid
      intradermally in the periareolar region. The first lymph node to appear on the
      scan was labeled as SLN and was marked on the skin by using a gamma probe. The
      lymph node was explored in the axilla using a gamma probe. RESULTS: The SLN was
      identified in all patients (100% success rate). Of 23 cases of DCIS on core
      biopsy, seven patients (30%) were shown to have invasive ductal carcinoma on
      final histological specimen. Among these seven patients, three had minimal
      invasive carcinoma (<1 cm) and none of these patients had positive SLN for
      metastases. Among 23 cases, only one patient with (4%) SLN was positive for
      metastasis despite histopathological diagnosis of pure DCIS. CONCLUSION: Although
      the study population is small, our findings suggest that patients with high-risk
      DCIS have an increased risk of invasive disease, as approximately one-third of
      these patients had invasive component at the time of definitive operative
      procedure. Furthermore, the study also suggests that SLNB appears to be reliable
      in identifying axillary lymph nodes status of these patients.

PMID- 21862943
TI  - Biological basis of [11C]choline-positron emission tomography in patients with
      breast cancer: comparison with [18F]fluorothymidine positron emission tomography.
AB  - OBJECTIVE: The biological significance of [11C]choline (CHO) uptake in human
      tumours is unclear and probably linked to choline kinase-alpha (CHKalpha)
      expression and cell proliferation. We directly compared CHO with
      [18F]fluorothymidine (FLT), an imaging biomarker of proliferation, by positron
      emission tomography (PET) in patients with breast cancer to investigate whether
      cell proliferation is an important determinant of CHO uptake. Furthermore, we
      evaluated CHKalpha and the Ki67-labelling index (LIKi67) in tumour biopsies.
      METHODS: Sequential CHO-PET and FLT-PET within the same imaging session were
      performed in 21 patients with oestrogen receptor (ER)-positive breast cancer (28
      lesions). Average and maximum CHO standardized uptake values (SUV) at 60 min:
      SUV60,av, and SUV60,max, and the rate constant of net irreversible uptake, Ki,
      were compared with FLT uptake at 60 min: SUV60,av and SUV60,max. Biopsies were
      stained for CHKalpha and LIKi67 in eight cases. RESULTS: Tumours were equally
      visible on CHO-PET and FLT-PET imaging. Tumour CHO-PET strongly correlated with
      FLT imaging variables (Pearson's r=0.83; P<0.0001 for CHO-SUV60,max vs. FLT
      SUV60,max). A statistically significant association was found between CHO-PET
      variables and categorical scores of cytoplasmic CHKalpha intensity and between
      FLT-PET and LIKi67 (P<0.05, one-way analysis of variance). CONCLUSION: Choline
      metabolism and proliferation as assessed by PET were correlated in ER-positive
      breast cancer, indicating that high CHO uptake is a measure of cellular
      proliferation in this setting. CHO uptake was also found to be related to
      cytoplasmic CHKalpha expression.

PMID- 21862944
TI  - Clinical utility of 18F-FDG PET parameters in patients with advanced
      nasopharyngeal carcinoma:  predictive role for different survival endpoints and
      impact on prognostic stratification.
AB  - OBJECTIVE: To investigate the prognostic impact of different 2-[fluorine
      18]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) parameters
      in patients with advanced nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: A
      total of 196 patients with primary stage III-IVb NPC were included in the study.
      The following parameters derived from pretreatment 18F-FDG PET were determined:
      metabolic tumor volume and total lesion glycolysis (TLG) of the primary tumor,
      maximal standardized uptake value of the primary tumor and the neck lymph nodes.
      Multivariable Cox proportional hazards models were used to identify independent
      predictors of survival. RESULTS: Multivariable analysis demonstrated that TLG
      values greater than 330 independently predicted overall survival (P=0.0014) and
      disease-free survival (P=0.0005). We identified IVa-b stage and TLG values
      greater than 330 as independent predictors of local failure-free survival. In
      addition, a high maximal standardized uptake value of the neck lymph nodes
      (P=0.005), male sex (P=0.041), and stage IVa-b (P=0.009) independently predicted
      distant failure-free survival. A TLG cutoff value of 330 allowed a better
      stratification of overall survival and disease-free survival rates. A scoring
      system combining significant PET parameters and traditional prognostic factors
      was formulated to define distinct prognostic groups for local failure-free
      survival and distant failure-free survival. There was a stepwise decrease in the
      5-year local (97.7, 90.4, and 47.3%, P<0.0001) and distant control rates (96.8,
      88.5, 73.9, and 36.4%, P<0.0001) according to the distinct prognostic scores.
      CONCLUSION: In patients with advanced NPC, the prognostic significance of 18F-FDG
      PET parameters seems to depend on the specific endpoint. The combination of PET
      metabolic parameters with traditional risk factors may significantly improve
      prognostic stratification for this group of patients.

PMID- 21862945
TI  - A preliminary report on (99m)Tc-fanolesomab imaging of renal allograft.
AB  - OBJECTIVE: To evaluate the utility of (99m)Tc-fanolesomab (a (99m)Tc-labeled
      murine monoclonal immunoglobulin M antibody that specifically binds cluster
      designation 15 antigens on human neutrophillic leukocytes with high sensitivity
      and specificity) in diagnosing localized infections. METHODS: Five patients with
      renal allografts were imaged using (99m)Tc-fanolesomab to look for a source of
      infection. Images were obtained between 2 and 4 h after injection of fanolesomab
      labeled with 15-20 mCi (99m)Tc. Imaging results were correlated with patients'
      culture results and clinical outcome. RESULTS: Two patients showed a significant
      increase in renal allograft uptake and were found to have allograft
      pyelonephritis. One patient who developed a severe acute renal failure secondary
      to humoral rejection (antidonor human leukocyte antigen antibody-mediated
      rejection with polymorphonuclear capillaritis and glomerulitis) showed uptake
      similar to the lower lumbar spine. One patient with normal allograft function
      showed a significantly increased uptake, especially in the pelvis of the
      allograft, indicating normal excretion of the free (99m)Tc-pertechnetate by the
      allograft. The fifth patient who had been off immunosuppressive therapy and on
      maintenance hemodialysis for 4 months showed tracer uptake similar to the lumbar
      spine, suggestive of chronic allograft rejection. CONCLUSION: This preliminary
      study describes different patterns of (99m)Tc-fanolesomab scan in renal
      allografts during episodes of kidney infection, rejection, or normal function. It
      suggests that (99m)Tc-fanolesomab can be used to evaluate renal allograft
      complications.

PMID- 21862946
TI  - Long-term results of tarsal margin rotation and extended posterior lamellae
      advancement for end stage trachoma.
AB  - PURPOSE: To report the long-term results of tarsal margin rotation with extended
      posterior lamellae advancement in the management of cicatricial entropion,
      trichiasis, and accompanying misdirected metaplastic lashes of the upper eyelid
      due to trachoma. METHODS: Tarsal margin rotation and extended advancement of
      posterior lamellae were performed in 27 eyelids of 15 consecutive patients for
      correction of cicatricial entropion, metaplastic lashes, and trichiasis. RESULTS:
      In all eyes, functional success, which was defined as normal mucocutaneous
      junction position and repositioning the lashes away from the ocular surface, were
      achieved. No recurrence was detected over a mean follow-up of 40.04 +/- 16.61
      (range, 18-72) months. Pyogenic granuloma, which was treated with complete
      excision, developed at the cut end of the tarsal conjunctiva in 3 cases. Cosmetic
      results were satisfactory in terms of both patients and examiner. CONCLUSION:
      Tarsal margin rotation with extended posterior lamellae advancement appears to be
      effective with no recurrence in managing cicatricial entropion and accompanying
      multiple eyelash problems of the upper eyelid due to trachoma.

PMID- 21862947
TI  - Severe visual loss and orbital infarction following periorbital aesthetic poly
      (L)-lactic acid (PLLA) injection.
AB  - Visual loss following esthetic treatment of the face is a rare but devastating
      iatrogenic complication. The authors report a case of a 43-year-old man with
      blindness and ophthalmoplegia of the left eye following a treatment of the left
      periorbital region with the subcutaneous filler poly-(L)-lactic acid. The
      patient's symptoms began immediately following one of the tunneled injections. On
      presentation, the patient had clear signs of ocular and orbital ischemia.
      Angiography and further history suggested an embolic orbital infarction as the
      mechanism of injury. The increased usage of subcutaneous fillers for facial
      rejuvenation had introduced a small but proven risk of embolization of these
      viscous materials to the eye and orbit.

PMID- 21862949
TI  - Cicatricial canthal webs.
AB  - INTRODUCTION: Cicatricial canthal webs present a complex reconstructive challenge
      for the eyelid surgeon. A combination of vertical skin deficiency, cutaneous and
      subcutaneous scar, and altered anatomy and blood supply can make surgical
      correction difficult and unpredictable. Patients typically are seen after
      blepharoplasty surgery or trauma with both cosmetic and functional (visual-field
      obstruction in lateral gaze) deficits. This is often a significant frustration to
      both the patient and the surgeon. A combination of a Y-to-V advancement flap,
      adjacent tissue rearrangement with Z-plasties centered on the arms of the Y (five
      flap technique), and scar excision, when necessary, can be a useful procedure for
      revision of these webs. METHODS: The charts of patients who underwent cicatricial
      canthal web revision in the solo private practice of the author over a 5-year
      period (2006-2010) were retrospectively reviewed. Each patient had a history of
      previous eyelid surgery or trauma that led to the development of the web. No
      patient had previous surgery to address the web. Each patient's presenting
      complaints were aesthetic, functional, or both, and each was previously told to
      avoid revision, as surgery to correct the web would make the condition worse.
      Patient's pre- and postrevision digital photographs, and patient and physician
      assessments, were reviewed to evaluate the results of surgery. Postoperative
      injections of subcutaneous steroid (Kenalog) and/or 5-fluorouracil (5-FU) were
      given as a treatment adjunct to modulate wound healing and prevent scarring when
      deemed appropriate. RESULTS: Eight patients were included in the study. Seven
      (88%) patients are women, and 1 (12%) patient is a man. The mean patient age is
      46 years (range, 18-56 years), and the mean follow-up is 17 months (range, 9-30
      months). Seven (88%) of the patients had lateral canthal webs after surgery, and
      1 (12%) patient had a medial canthal web after a motor vehicle accident. Every
      patient voiced aesthetic concerns with the web, and 4 (57%) of the 7 patients
      with lateral canthal webs reported a visual deficit related to the defect. Six
      (75%) patients received 3 separate injections of Kenalog postoperatively, and 2
      (25%) patients received the same number of injections composed primarily of 5-FU
      admixed with steroid. Each patient was satisfied with the aesthetic and
      functional result of surgery. CONCLUSION: Cicatricial canthal webs are an
      uncommonly reported finding that has received little attention in the literature.
      The condition has both aesthetic and functional implications, can be very
      bothersome and frustrating to patients, and can be intimidating to the treating
      surgeon. Although surgical revision carries risks of flap necrosis, scar, and
      worsened appearance, it can also significantly improve appearance and function.
      If the patient is realistic, understands the limitation of surgery, and will be
      happy with a moderate improvement, surgery should be strongly considered. The
      author found that revision of cicatricial canthal webs with the technique
      described in this article yields excellent results, given the limitations of the
      presenting problem.

PMID- 21862948
TI  - Giant fornix syndrome:  a case series.
AB  - PURPOSE: To describe the demographics, characteristics, and treatment of giant
      fornix syndrome, a rare cause of chronic purulent conjunctivitis in the elderly.
      METHODS: Retrospective chart review of five patients with giant fornix syndrome
      evaluated by the Cornea Service, Oculoplastics and Orbital Surgery Service and
      the Department of Pathology at the Wills Eye Institute. RESULTS: The median age
      of the 5 female patients was 75 years (mean 80, range 70-95). The median duration
      of eye symptoms before presentation was 2 years (mean 2.4, range 1-4). Before
      referral, the chronic conjunctivitis was treated with topical antibiotics in all
      5 cases and with additional dacryocystorhinostomy in one case. The right eye was
      affected in 2 cases, and the left eye was affected in the other 3 cases. Floppy
      eyelids were present in 2 cases. The superior fornix was involved in 4 cases, and
      the inferior fornix was involved in one case. Pseudomembranes and superficial
      punctate keratitis (SPK) were seen in 3 cases. Diagnosis of giant fornix syndrome
      was made in all 5 cases. Conjunctival culture grew methicillin-resistant
      Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and S. aureus in singular
      cases. Case 1 was treated with topical moxifloxacin, Case 2 was treated with
      topical vancomycin and repair of the upper eyelid, Case 3 was treated with
      topical besifloxacin, and Case 4 was treated with dacryocystorhinostomy and
      topical vancomycin. Case 5 was treated with reconstruction of the left upper
      eyelid. The median duration of follow up was 4 months (mean 21.6, range 1-84).
      CONCLUSIONS: Giant fornix syndrome can lead to chronic relapsing conjunctivitis
      in the elderly. Deep conjunctival fornices in affected patients can be a site for
      prolonged sequestration of bacteria causing recurrent infections. Removing the
      infected debris from the superior fornix and reconstruction of the upper eyelid
      may prevent the recurrent chronic persistent infection.

PMID- 21862950
TI  - A nonconservative amino acid change in the UPF3B gene in a patient with
      schizophrenia.

PMID- 21862951
TI  - Influence of 5-HTTLPR and 5-HTTVNTR polymorphisms of the serotonin transporter
      gene (SLC6A4) on major depressive disorder in a sample of Argentinean population.

PMID- 21862952
TI  - Association between schizophrenia and single nucleotide polymorphisms in
      lipoprotein lipase gene in a Han Chinese population.
AB  - OBJECTIVE: Many studies have suggested that certain types of lipids such as
      phospholipids, fatty acids, and cholesterols are involved in the pathology of
      nervous system diseases. Lipoprotein lipase (LPL), as the key enzyme of
      triglyceride hydrolysis, is expressed in the brain regions functionally relevant
      to learning, memory, and other cognitive functions. In addition, both genome-wide
      linkage and association studies in schizophrenia have implicated the chromosome
      8p22 region, in which the LPL gene is located. Therefore, LPL is an attractive
      candidate gene for schizophrenia and we tested this hypothesis in a case-control
      sample. METHODS: In this study, we investigated allele and genotype frequencies
      distributions of nine single nucleotide polymorphisms (SNPs) within the LPL gene
      in Han Chinese patients with schizophrenia (n=319) and healthy controls (n=575).
      RESULTS: Significant differences were detected between case and control groups in
      the frequencies of rs253 alleles [odds ratio (OR): 1.74; 95% confidence interval
      (CI): 1.43-2.11; P=3.21*10] and genotypes (OR: 3.08; 95%CI: 2.07-4.56; global
      P=7.88*10), respectively. Interestingly, this association was observed only in
      the male (P=5.87*10 for allele; P=1.79*10 for genotype) and not in the female
      samples (P>0.05). After correcting for multiple testing, the above association
      remains to be significant (Pc<1*10). These results suggest that rs253 C allele
      and CC genotype confer risk for schizophrenia in men. CONCLUSION: Our study lends
      support to the potential role of lipid metabolism in schizophrenia and further
      investigations are warranted.

PMID- 21862953
TI  - Prospective randomized controlled trial of combination ranibizumab (Lucentis) and
      bromfenac (Xibrom) for neovascular age-related macular degeneration: a pilot
      study.
AB  - PURPOSE: To evaluate whether bromfenac eyedrops and ranibizumab intravitreal
      injections would provide added efficacy over ranibizumab alone. METHODS: This was
      a single-site, multiinvestigator, prospective, open-label, interventional, Phase
      II study of patients with new or recurrent exudative/neovascular age-related
      macular degeneration. Thirty eyes were enrolled consecutively and were randomized
      in a ratio of 2:1 to combination therapy with intravitreal ranibizumab and
      topical bromfenac, and ranibizumab alone. All patients received ranibizumab
      monthly therapy for 4 months then as needed monthly in accordance with standard
      of care. Patients receiving bromfenac self-administered 1 drop twice a day for 12
      months. Patients were followed for 12 months. RESULTS: There were no safety
      concerns with the combination therapy. No statistically significant differences
      were identified in Early Treatment Diabetic Retinopathy Study best-corrected
      visual acuity or the number of injections required. However, the mean 12-month
      change in central macular thickness in the combination group was -81.56 MUm while
      in the ranibizumab group alone the change was -42.50 MUm (P = 0.03). The
      proportion of eyes experiencing a decrease in CMT of 50 MUm or more was also
      significantly higher in those receiving combination therapy (P = 0.046).
      CONCLUSION: This pilot study is the first to prospectively identify a biologic
      signal that may indicate combination therapy with an easily administered well
      tolerated eyedrop and ranibizumab is efficacious for the treatment of neovascular
      age-related macular degeneration. Further studies are warranted to validate this
      finding.

PMID- 21862955
TI  - Impact of de novo everolimus-based immunosuppression on incisional complications
      in heart transplantation.
AB  - BACKGROUND: The mammalian target of rapamycin inhibitor sirolimus has been
      associated with an increased incidence of wound-healing complications after de
      novo heart transplantation. To evaluate the possibility of a similar association
      for everolimus, we performed a risk-factor analysis to compare the incidence of
      incision-related wound complications for everolimus with that of other adjunctive
      drugs. METHODS: Safety data from 1009 heart transplant recipients (n=214,
      receiving azathioprine; n=84, mycophenolate mofetil (MMF); n=711, everolimus)
      were reviewed in a post hoc analysis from three randomized, multicenter studies
      B253 (n=634), A2403 (n=199), and A2411 (n=176)-in which de novo patients received
      fixed-dose or concentration-controlled everolimus (target trough, 3-8 ng/mL),
      azathioprine, or MMF with standard- or reduced-exposure cyclosporine A.
      Incisional complications were analyzed for incidence, type, and severity up to
      day 90 posttransplant. RESULTS: Incisional-complication events occurred in 25
      (11.7%) azathioprine, six (7.2%) MMF, and 87 (12.3%) everolimus patients. Serious
      incisional complications were more frequent with everolimus (6.9%) compared with
      azathioprine (4.2%; P=0.197) or MMF (1.2%; P=0.051). In a univariate analysis,
      patient sex, body mass index (BMI), and diabetes were associated with incisional
      complications. Only BMI was significantly associated with incisional
      complications in the subsequent multivariate analysis, with the odds of an
      incisional-complication event increasing by 12.9% for every 1 kg/m increase in
      BMI (P<0.001). CONCLUSIONS: The incidence of incisional complications with
      everolimus was generally low, although numerically higher compared with MMF. Our
      analyses provided no strong evidence that everolimus is an independent risk
      factor for incisional complications. After de novo heart transplantation,
      patients with a high BMI are at higher risk of incision-related wound
      complications.

PMID- 21862954
TI  - Oral protein kinase c beta inhibition using ruboxistaurin: efficacy, safety, and
      causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy
      in the Protein Kinase C beta Inhibitor-Diabetic Retinopathy Study and the Protein
      Kinase C beta Inhibitor-Diabetic Retinopathy Study 2.
AB  - PURPOSE: To evaluate efficacy, safety, and causes of vision loss among 813
      patients (1,392 eyes) with moderately severe to very severe nonproliferative
      diabetic retinopathy from the Protein Kinase C beta Inhibitor-Diabetic
      Retinopathy Study and Protein Kinase C beta Inhibitor-Diabetic Retinopathy Study
      2 ruboxistaurin (RBX) protein kinase C beta inhibitor trials. METHODS: Patients
      in these 3-year, randomized, placebo-controlled, double-masked, Phase 3 trials
      had best-corrected Early Treatment Diabetic Retinopathy Study visual acuity >=45
      letters (~20/125 Snellen), Early Treatment Diabetic Retinopathy Study retinopathy
      level 47A/B-53E, and no previous panretinal photocoagulation in >=1 eye. Patients
      received placebo (N = 401) or RBX 32 mg/day (N = 412). Data from the 2 studies
      were combined and masked evaluation of retinal photographs was performed for
      cause of visual decline in all patients experiencing sustained moderate visual
      loss (>=15-letter loss sustained for the last 6 months of study). RESULTS: In the
      studies combined, sustained moderate visual loss occurred in 10.2% of placebo
      treated patients versus 6.1% of RBX-treated patients (P = 0.011). A >=15-letter
      gain occurred in 2.4% of placebo versus 4.7% of RBX eyes (P = 0.021) and a >=15
      letter loss occurred in 11.4% versus 7.4%, respectively (P = 0.012). Diabetic
      macular edema was the probable primary cause of vision loss. Among eyes without
      focal/grid photocoagulation at baseline, fewer RBX group eyes (26.7%) required
      initial focal/grid photocoagulation versus placebo (35.6%; P = 0.008). No safety
      concerns were identified. CONCLUSION: Analysis of data combined from two similar
      studies adds further statistical significance to RBX's beneficial effects on
      visual loss, need for focal laser, and vision gain, most likely through effects
      on macular edema.

PMID- 21862956
TI  - Physico-chemical characteristics and functional properties of chitin and chitosan
      produced by Mucor circinelloides using yam bean as substrate.
AB  - Microbiological processes were used for chitin and chitosan production by Mucor
      circinelloides (UCP 050) grown in yam bean (Pachyrhizus erosus L. Urban) medium.
      The polysaccharides were extracted by alkali-acid treatment and structural
      investigations by X-ray diffraction, Fourier transform IR analysis, viscosity and
      thermal analysis by TG, DTG, and DTA were done. The highest biomass yield (20.7
      g/L) was obtained at 96 hours. The highest levels of chitosan (64 mg/g) and
      chitin (500 mg/g) were produced at 48 and 72 hours, respectively. It was
      demonstrated that yam bean shows great potential as an economic medium and it is
      possible to achieve a good yield of chitosan with chemical properties that enable
      its use in biotechnological applications.

PMID- 21862957
TI  - The growth suppressing effects of girinimbine on HepG2 involve induction of
      apoptosis and cell cycle arrest.
AB  - Murraya koenigii is an edible herb widely used in folk medicine. Here we report
      that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the
      growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The
      MTT and LDH assay results showed that girinimbine decreased cell viability and
      increased cytotoxicity in a dose-and time-dependent manner selectively.
      Girinimbine-treated HepG2 cells showed typical morphological features of
      apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay.
      Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated
      levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time
      dependent accumulation of the Sub-G(0)/G(1) peak (hypodiploid) and caused
      G(0)/G(1)-phase arrest. Together, these results demonstrated for the first time
      that girinimbine could effectively induce programmed cell death in HepG2 cells
      and suggests the importance of conducting further investigations in preclinical
      human hepatocellular carcinoma models, especially on in vivo efficacy, to promote
      girinimbine for use as an anticancer agent against hepatocellular carcinoma.

PMID- 21862958
TI  - Optimized enzymatic synthesis of hesperidin fatty acid esters in a two-phase
      system containing ionic liquid.
AB  - Response surface methodology (RSM) based on a five-level, three-variable central
      composite design (CCD) was employed for modeling and optimizing the conversion
      yield of the enzymatic acylation of hesperidin with decanoic acid using
      immobilized Candida antarctica lipase B (CALB) in a two-phase system containing
      [bmim]BF(4). The three variables studied (molar ratio of hesperidin to decanoic
      acid, [bmim]BF(4)/acetone ratio and lipase concentration) significantly affected
      the conversion yield of acylated hesperidin derivative. Verification experiments
      confirmed the validity of the predicted model. The lipase showed higher
      conversion degree in a two-phase system using [bmim]BF(4) and acetone compared to
      that in pure acetone. Under the optimal reaction conditions carried out in a
      single-step biocatalytic process when the water content was kept lower than 200
      ppm, the maximum acylation yield was 53.6%.

PMID- 21862960
TI  - Optimizing cancer care: is the future bright?

PMID- 21862965
TI  - Investigative clinical pharmacology.
AB  - Clinical pharmacology is an essential discipline in the development of new
      medicines, but the closely specified requirements of pharmaceutical industry
      protocols and regulatory reviewers have limited the opportunities for curiosity
      driven research. Realization is growing that there is so much that is not known
      about the mechanisms underlying human disease and the actions of medicines on
      them that research of a more exploratory kind, namely, investigative clinical
      pharmacology, is a priority.

PMID- 21862966
TI  - Improving the use of allopurinol in chronic gout: monitoring oxypurinol levels to
      guide therapy.
AB  - Urate-lowering therapy (ULT), adjusted to achieve and maintain a serum uric acid
      (SUA) of <6 mg/dl, remains the standard of care for the chronic management of
      gout. New urate-lowering medications are important options; however, these agents
      should be reserved for patients who do not tolerate or cannot achieve SUA <6
      mg/dl on allopurinol. The result of oxypurinol monitoring to guide allopurinol
      therapy suggests that allopurinol should still be considered first-line ULT for
      gout.

PMID- 21862970
TI  - TGFbeta inhibition enhances the generation of hematopoietic progenitors from
      human ES cell-derived hemogenic endothelial cells using a stepwise strategy.
AB  - Embryonic hematopoiesis is a complex process. Elucidating the mechanism
      regulating hematopoietic differentiation from pluripotent stem cells would allow
      us to establish a strategy to efficiently generate hematopoietic cells. However,
      the mechanism governing the generation of hematopoietic progenitors from human
      embryonic stem cells (hESCs) remains unknown. Here, on the basis of the emergence
      of CD43(+) hematopoietic cells from hemogenic endothelial (HE) cells, we
      demonstrated that VEGF was essential and sufficient, and that bFGF was
      synergistic with VEGF to specify the HE cells and the subsequent transition into
      CD43(+) hematopoietic cells. Significantly, we identified TGFbeta as a novel
      signal to regulate hematopoietic development, as the TGFbeta inhibitor SB 431542
      significantly promoted the transition from HE cells into CD43(+) hematopoietic
      progenitor cells (HPCs) during hESC differentiation. By defining these critical
      signaling factors during hematopoietic differentiation, we can efficiently
      generate HPCs from hESCs. Our strategy could offer an in vitro model to study
      early human hematopoietic development.

PMID- 21862971
TI  - Mouse miRNA-709 directly regulates miRNA-15a/16-1 biogenesis at the
      posttranscriptional level in the nucleus: evidence for a microRNA hierarchy
      system.
AB  - MicroRNAs (miRNAs) are endogenous noncoding RNAs (~22 nt) that regulate target
      gene expression at the post-transcriptional level in the cytoplasm. Recent
      discoveries of the presence of miRNAs and miRNA function-required argonaute
      family proteins in the cell nucleus have prompted us to hypothesize that miRNAs
      may also have regulatory functions in the cell nucleus. In this study, we
      demonstrate that mouse miR-709 is predominantly located in the nucleus of various
      cell types and that its nuclear localization pattern rapidly changes upon
      apoptotic stimuli. In the cell nucleus, miR-709 directly binds to a 19-nt miR-709
      recognition element on pri-miR-15a/16-1 and prevents its processing into pre-miR
      15a/16-1, leading to a suppression of miR-15a/16-1 maturation. Furthermore,
      nuclear miR-709 participates in the regulation of cell apoptosis through the miR
      15a/16-1 pathway. In summary, the present study provides the first evidence that
      one miRNA can control the biogenesis of other miRNAs by directly targeting their
      primary transcripts in the nucleus.

PMID- 21862972
TI  - Active DNA demethylation by oxidation and repair.

PMID- 21862973
TI  - The critical role of CD133(+)CD44(+/high) tumor cells in hematogenous metastasis
      of liver cancers.
AB  - Metastatic hepatocellular carcinoma (HCC) is one of the most lethal cancers
      worldwide. However, the cell population responsible for its metastasis remains
      largely unknown. Here, we reported that CD133(+)CD44(+/high) defined a subgroup
      of tumor cells that was responsible for hematogenous metastasis of liver cancers.
      Immunohistochemical investigation of human HCC specimens revealed that the number
      of CD133(+) and CD44(+) HCC cells was increased and was associated with portal
      vein invasion. Purified CD133(+) or CD44(high) HCC cells were superior in
      clonogenic growth and vascular invasion, respectively. Thus, the combination of
      CD133 and CD44 was used to define a novel HCC sub-population. CD133(+)CD44(high),
      but not CD133(+)CD44(low/-), CD133(-)CD44(high) or CD133(-)CD44(low/-)
      xenografts, produced intrahepatic or lung metastasis in nude mice. Further
      analysis of human HCC samples by flow cytometry showed that the number of
      CD133(+)CD44(+) tumor cells was associated with portal vein metastasis. The cDNA
      microarray analysis of CD133(+)CD44(+) and CD133(+)CD44(-) tumor cells isolated
      from metastatic HCC patients revealed that these cells comprised of two different
      populations possessing distinct gene expression profiles. Our results suggest
      that CD133(+)CD44(+) tumor cells are a particular population responsible for
      hematogenous metastasis in liver cancers and that these cells might be targets
      for treatment of HCC metastasis.

PMID- 21862974
TI  - High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based
      HAART-induced liver injury in the treatment of naive HIV patients from Ethiopia:
      a prospective cohort study.
AB  - The objective of this study was to assess the incidence, timing and identify
      pharmacogenetic, efavirenz (EFV) pharmacokinetic and biochemical predictors of
      EFV-based antiretroviral therapy (ART) drug-induced liver injury (DILI). ART
      naive HIV patients (n = 285) were prospectively enrolled. Pretreatment laboratory
      evaluations included hepatitis B surface antigen and C antibody, CD4 count and
      viral load. Liver tests were done at baseline, 1st, 2nd, 4th, 8th, 12th, 24th and
      48th weeks during ART. Plasma EFV and 8-hydroxyefvairenz concentration was
      determined at week 4 using liquid chromatography-mass spectrometry. CYP2B6,
      CYP3A5, ABCB1 3435C/T and UGT2B7*2 genotyping was done using Taqman genotyping
      assay. Data were analyzed using survival analysis and Cox proportional hazards
      model. The incidence of DILI was 15.7% or 27.9 per 100 person-years and that of
      severe injury was 3.4% or 6.13 per 100 person-years. The median time for the
      development of DILI and severe injury was 2 and 4 weeks after initiation of ART,
      respectively. There was significant association of DILI with lower baseline
      platelet, albumin, log plasma viral load and CD4 count (P = 0.031, 0.037, 0.06
      and 0.019, respectively). Elevated baseline alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, plasma EFV level and CYP2B6*6 were good
      predictors for the development of DILI (P = 0.03, 0.01, 0.016, 0.017 and 0.04,
      respectively). We report for the first time CYP2B6*6 as a putative genetic marker
      and high plasma EFV concentration as intermediate biomarker for vulnerability to
      EFV-induced liver injury in HIV patients. CYP2B6 genotyping and/or regular
      monitoring of EFV and lever enzymes level during early therapy is advised for
      early diagnosis and management of DILI.

PMID- 21862975
TI  - Congenital heart conditions: Clear benefits of pulse oximetry in neonates--one
      small step to improving postnatal cardiac care.

PMID- 21862977
TI  - Screening: Reduced breast cancer mortality rates in Europe are not due to
      screening.

PMID- 21862976
TI  - Genetics of vesicoureteral reflux.
AB  - Primary vesicoureteral reflux (VUR) is the most common urological anomaly in
      children, affecting 1-2% of the pediatric population and 30-40% of children
      presenting with urinary tract infections (UTIs). Reflux-associated nephropathy is
      a major cause of childhood hypertension and chronic renal failure. The hereditary
      and familial nature of VUR is well recognized and several studies have reported
      that siblings of children with VUR have a higher incidence of reflux than the
      general pediatric population. Familial clustering of VUR implies that genetic
      factors have an important role in its pathogenesis, but no single major locus or
      gene for VUR has yet been identified and most researchers now acknowledge that
      VUR is genetically heterogeneous. Improvements in genome-scan techniques and
      continuously increasing knowledge of the genetic basis of VUR should help us to
      further understand its pathogenesis.

PMID- 21862979
TI  - Signal transduction: The old dog's new tricks.

PMID- 21862978
TI  - Predictive biomarkers: a paradigm shift towards personalized cancer medicine.
AB  - Advances in our understanding of the intricate molecular mechanisms for
      transformation of a normal cell to a cancer cell, and the aberrant control of
      complementary pathways, have presented a much more complex set of challenges for
      the diagnostic and therapeutic disciplines than originally appreciated. The
      oncology field has entered an era of personalized medicine where treatment
      selection for each cancer patient is becoming individualized or customized. This
      advance reflects the molecular and genetic composition of the tumors and progress
      in biomarker technology, which allow us to align the most appropriate treatment
      according to the patient's disease. There is a worldwide acceptance that advances
      in our ability to identify predictive biomarkers and provide them as companion
      diagnostics for stratifying and subgrouping patients represents the next leap
      forward in improving the quality of clinical care in oncology. As such, we are
      progressing from a population-based empirical 'one drug fits all' treatment
      model, to a focused personalized approach where rational companion diagnostic
      tests support the drug's clinical utility by identifying the most responsive
      patient subgroup.

PMID- 21862981
TI  - Diagnosis: Liver biopsy differentiates DILI from autoimmune hepatitis.

PMID- 21862980
TI  - Personalized medicine in lung cancer: what we need to know.
AB  - Lung cancer is a complex and often fatal disease. The recent discovery of
      activating mutations in EGFR and fusion genes involving ALK has set the stage for
      personalized medicine for lung cancer. Patients selected using biomarkers have
      benefited from the development of EGFR tyrosine kinase inhibitors and ALK
      inhibitors with considerable improvement in tumor control and survival. Four key
      areas of knowledge that are essential to the development of targeted therapy are
      discussed in this Review: knowing the target, knowing the biomarker, knowing the
      end point and knowing the mechanisms of resistance.

PMID- 21862982
TI  - Diagnosis of cognitive impairment in adult and pediatric SLE.

PMID- 21862984
TI  - Lipid biomarkers for early-stage Alzheimer disease.

PMID- 21862983
TI  - The microbiome and rheumatoid arthritis.
AB  - Humans are not (and have never been) alone. From the moment we are born, millions
      of micro-organisms populate our bodies and coexist with us rather peacefully for
      the rest of our lives. This microbiome represents the totality of micro-organisms
      (and their genomes) that we necessarily acquire from the environment. Micro
      organisms living in or on us have evolved to extract the energy they require to
      survive, and in exchange they support the physiological, metabolic and immune
      capacities that have contributed to our evolutionary success. Although currently
      categorized as an autoimmune disorder and regarded as a complex genetic disease,
      the ultimate cause of rheumatoid arthritis (RA) remains elusive. It seems that
      interplay between predisposing genetic factors and environmental triggers is
      required for disease manifestation. New insights from DNA sequence-based analyses
      of gut microbial communities and a renewed interest in mucosal immunology suggest
      that the microbiome represents an important environmental factor that can
      influence autoimmune disease manifestation. This Review summarizes the historical
      clues that suggest a possible role for the microbiota in the pathogenesis of RA,
      and will focus on new technologies that might provide scientific evidence to
      support this hypothesis.

PMID- 21862985
TI  - ALCAM as a prognostic marker for acute ischemic stroke.

PMID- 21862988
TI  - High-frequency oscillations pinpoint the seizure-onset zone.

PMID- 21862989
TI  - New pathogenetic insights into Charcot-Marie-Tooth disease.

PMID- 21862990
TI  - Why kidneys fail in autosomal dominant polycystic kidney disease.
AB  - The weight of evidence gathered from studies in humans with hereditary polycystic
      kidney disease (PKD)1 and PKD2 disorders, as well as from experimental animal
      models, indicates that cysts are primarily responsible for the decline in
      glomerular filtration rate that occurs fairly late in the course of the disease.
      The processes underlying this decline include anatomic disruption of glomerular
      filtration and urinary concentration mechanisms on a massive scale, coupled with
      compression and obstruction by cysts of adjacent nephrons in the cortex, medulla
      and papilla. Cysts prevent the drainage of urine from upstream tributaries, which
      leads to tubule atrophy and loss of functioning kidney parenchyma by mechanisms
      similar to those found in ureteral obstruction. Cyst-derived chemokines,
      cytokines and growth factors result in a progression to fibrosis that is
      comparable with the development of other progressive end-stage renal diseases.
      Treatment of renal cystic disorders early enough to prevent or reduce cyst
      formation or slow cyst growth, before the secondary changes become widespread, is
      a reasonable strategy to prolong the useful function of kidneys in patients with
      autosomal dominant polycystic kidney disease.

PMID- 21862992
TI  - Transplantation: pre-emptive kidney transplantation--perfect, but when?

PMID- 21862993
TI  - Diabetes: bardoxolone improves kidney function in type 2 diabetes.

PMID- 21862991
TI  - Noninvasive imaging for assessment of calcification in chronic kidney disease.
AB  - Vascular calcification is highly prevalent in patients with chronic kidney
      disease and has a progressive course. Several cardiovascular and uremia-related
      risk factors, such as abnormalities in mineral metabolism, contribute to the
      development of vascular calcification, although the pathophysiological mechanisms
      are still unclear. The presence and extent of vascular calcification is
      associated with an increased risk of cardiovascular events and mortality. By
      contrast, patients who do not have calcification seem to have a good prognosis,
      with minimal or no calcification progression over an extended period of time. A
      number of noninvasive imaging methods are available to detect vascular
      calcification and may help clinicians to make therapeutic decisions. Cardiac CT
      remains the reference standard to detect and quantify coronary artery, aortic and
      cardiac valve calcification. However, the high cost of equipment, the inability
      to perform in-office testing and the expertise required limit its use on a
      routine basis. Other imaging methods, such as planar X-ray, ultrasound and
      echocardiography, are appropriate alternatives to evaluate vascular and valvular
      calcification. In this review, we discuss the noninvasive imaging methods most
      frequently used to assess vascular and valvular calcification, with their
      advantages and limitations.

PMID- 21862994
TI  - Management of medullary thyroid carcinoma and MEN2 syndromes in childhood.
AB  - Medullary thyroid carcinoma (MTC) and the multiple endocrine neoplasia (MEN) type
      2 syndromes are rare but important endocrine diseases that are increasingly
      managed by pediatric providers. MTC is generally associated with a favorable
      prognosis when diagnosed during childhood, where it frequently occurs secondary
      to activating mutations in the RET proto-oncogene and arises from pre-existing C
      cell hyperplasia. MEN2A accounts for 90-95% of childhood MTC cases and is most
      commonly due to mutations in codon 634 of RET. MEN2B is associated with the most
      aggressive clinical presentation of MTC and is almost always due to the Met918Thr
      mutation of RET. Surgery is the primary treatment and only chance of cure,
      although the advent of targeted therapies seems to be improving progression-free
      survival in advanced cases. Since the discovery of the role of RET in MEN2A,
      considerable advances in the management of this syndrome have occurred, and most
      of the children with MEN2A who have undergone early thyroidectomy will now lead
      full, productive lives. Strong genotype-phenotype correlations have facilitated
      the development of guidelines for interventions. Contemporary approaches for
      deciding the appropriate age at which surgery should take place incorporate data
      from ultrasonography and calcitonin measurements in addition to the results of
      genotyping. To optimize care and to facilitate ongoing research, children with
      MTC and the MEN2 syndromes are optimally treated at tertiary centers with
      multidisciplinary expertise.

PMID- 21862995
TI  - Multikinase inhibitors: a new option for the treatment of thyroid cancer.
AB  - Thyroid cancer typically has a good outcome following standard treatments, which
      include surgery, radioactive iodine ablation and treatment with TSH-suppressive
      levothyroxine. Thyroid cancers that persist or recur following these therapies
      have a poorer prognosis. Activation of mitogenic and angiogenic signaling
      pathways occurs in these cancers, and preclinical models have shown that
      inhibition of key kinase steps in these pathways can have antitumoral effects.
      Several of these kinase inhibitors have now been tested in phase II and phase III
      trials, with modestly encouraging results. Some promising data exist for the use
      of vandetanib (also known as ZD6474), motesanib, axitinib, cabozantinib (also
      known as XL184), sorafenib, sunitinib, pazopanib and lenvatinib (also known as
      E7080) in progressive thyroid cancer of medullary, papillary and follicular
      subtypes. These drugs are generally well-tolerated, although dose-limiting
      toxicities are common, and a few (probable) treatment-related deaths have been
      reported. Additional phase III trials will be needed to conclusively show that
      treatment benefit exceeds risk. Drug resistance can occur via activation of
      alternate mitogenic signals (pathway switching), as has been reported for the use
      of kinase inhibitors in other malignancies, such as melanoma. The hypothesis that
      combinations of kinase inhibitors targeting different pathways might produce
      better results is currently being tested in several clinical trials.

PMID- 21862996
TI  - Advances in surgical therapy for thyroid cancer.
AB  - Thyroid cancer is the most common malignancy of the endocrine system and its
      incidence has dramatically increased over the past three decades. Well
      differentiated thyroid cancers (DTCs) are the main focus of this article, as they
      represent >90% of thyroid malignancies. This Review provides an overview of the
      controversies surrounding the optimal choice of surgery and extent of resection
      for patients with low-risk DTC or with papillary thyroid microcarcinoma, and the
      role of prophylactic central lymph node dissection. This Review also outlines the
      current surgical management of DTC and presents updated results for these
      techniques, along with important advances and current dilemmas in surgical
      approaches to treatment of these cancers. For example, endoscopic and robotic
      thyroidectomy are the two most recent innovations to present technical and other
      challenges to the endocrine surgeon; in addition, the risks as well as the
      advantages of same-day thyroid surgery, which has gained some acceptance, are
      detailed. Arguments for and against each approach are presented, along with
      supporting evidence. The authors' personal opinions are also provided for each
      topic.

PMID- 21862997
TI  - Inflammatory bowel disease of the elderly: frequently asked questions (FAQs).
AB  - The growing recognition of the older inflammatory bowel disease (IBD) patient is
      heightened by the entry of the 77.2 million baby boomers who will turn 65
      beginning of 2011. It is anticipated that this will occur at a rate of 10,000 per
      day or 4 million per year for the next 19 years. The management of IBD in this
      population is complex because of problems with co-morbidities, polypharmacy,
      impaired mobility, and cognition, as well as difficult social and financial
      issues. This review focuses on the older IBD patient's unique concerns and
      provides guidance in their diagnosis and management.

PMID- 21862998
TI  - Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen
      MSP1 in ChAd63 and MVA vaccine vectors.
AB  - Efficacy trials of antibody-inducing protein-in-adjuvant vaccines targeting the
      blood-stage Plasmodium falciparum malaria parasite have so far shown
      disappointing results. The induction of cell-mediated responses in conjunction
      with antibody responses is thought to be one alternative strategy that could
      achieve protective efficacy in humans. Here, we prepared chimpanzee adenovirus 63
      (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient vectors
      encoding the well-studied P. falciparum blood-stage malaria antigen merozoite
      surface protein 1 (MSP1). A phase Ia clinical trial was conducted in healthy
      adults of a ChAd63-MVA MSP1 heterologous prime-boost immunization regime. The
      vaccine was safe and generally well tolerated. Fewer systemic adverse events
      (AEs) were observed following ChAd63 MSP1 than MVA MSP1 administration.
      Exceptionally strong T-cell responses were induced, and these displayed a mixed
      of CD4(+) and CD8(+) phenotype. Substantial MSP1-specific serum immunoglobulin G
      (IgG) antibody responses were also induced, which were capable of recognizing
      native parasite antigen, but these did not reach titers sufficient to neutralize
      P. falciparum parasites in vitro. This viral vectored vaccine regime is thus a
      leading approach for the induction of strong cellular and humoral immunogenicity
      against difficult disease targets in humans. Further studies are required to
      assess whether this strategy can achieve protective efficacy against blood-stage
      malaria infection.

PMID- 21862999
TI  - Insertion sites in engrafted cells cluster within a limited repertoire of genomic
      areas after gammaretroviral vector gene therapy.
AB  - Vector-associated side effects in clinical gene therapy have provided insights
      into the molecular mechanisms of hematopoietic regulation in vivo. Surprisingly,
      many retrovirus insertion sites (RIS) present in engrafted cells have been found
      to cluster nonrandomly in close association with specific genes. Our data
      demonstrate that these genes directly influence the in vivo fate of hematopoietic
      cell clones. Analysis of insertions thus far has been limited to individual
      clinical studies. Here, we studied >7,000 insertions retrieved from various
      studies. More than 40% of all insertions found in engrafted gene-modified cells
      were clustered in the same genomic areas covering only 0.36% of the genome. Gene
      classification analyses displayed significant overrepresentation of genes
      associated with hematopoietic functions and relevance for cell growth and
      survival in vivo. The similarity of insertion distributions indicates that vector
      insertions in repopulating cells cluster in predictable patterns. Thus, insertion
      analyses of preclinical in vitro and murine in vivo studies as well as vector
      insertion repertoires in clinical trials yielded concerted results and mark a
      small number of interesting genomic loci and genes that warrants further
      investigation of the biological consequences of vector insertions.

PMID- 21863000
TI  - Adenovirus i-leader truncation bioselected against cancer-associated fibroblasts
      to overcome tumor stromal barriers.
AB  - Tumor-associated stromal cells constitute a major hurdle in the antitumor
      efficacy with oncolytic adenoviruses. To overcome this biological barrier, an in
      vitro bioselection of a mutagenized AdwtRGD stock in human cancer-associated
      fibroblasts (CAFs) was performed. Several rounds of harvest at early cytopathic
      effect (CPE) followed by plaque isolation led us to identify one mutant with
      large plaque phenotype, enhanced release in CAFs and enhanced cytotoxicity in CAF
      and several tumor cell lines. Whole genome sequencing and functional mapping
      identified the truncation of the last 17 amino acids in C-terminal end of the i
      leader protein as the mutation responsible for this phenotype. Similar mutations
      have been previously isolated in two independent bioselection processes in tumor
      cell lines. Importantly, our results establish the enhanced antitumor activity in
      vivo of the i-leader C-terminal truncated mutants, especially in a desmotic
      fibroblast-embedded lung carcinoma model in mice. These results indicate that the
      i-leader truncation represents a promising trait to improve virotherapy with
      oncolytic adenoviruses.

PMID- 21863001
TI  - Expression of gamma-chain cytokine receptors on CD8+ T cells in HIV infection
      with a focus on IL-7Ralpha (CD127).
AB  - When interleukin-2 (IL-2) receptor gamma-chain (gamma(C))-sharing cytokine
      receptors on T cells bind their specific ligands (IL-2, -4, -7, -9, -15 or -21),
      they initiate a variety of cell signals that promote survival, differentiation or
      antiviral or antitumor cytolytic functions. Although expression of the gamma(C)
      is constitutive across T-cell subsets, the varying expression of other receptor
      complex components can regulate cytokine signalling and function. Impaired
      gamma(C) cytokine activity in HIV infection, and the role of gamma(C) cytokines
      in CD8(+) T-cell function and homeostasis, implicates these molecules among
      potential contributors to the observed decline of cytolytic activity (CTL) in HIV
      disease. In particular, this review will be highlighting information about the IL
      7 receptor (IL-7R) complex, which is composed of the gamma(C) and the IL-7Ralpha
      (CD127) chains. There has been an abundance of HIV-related CD127 research and its
      important role in CD8(+) T-cell survival and function. The expression of CD127
      undergoes dramatic changes throughout the course of T-cell responses in HIV
      infection. The expression of CD127 is significantly decreased in progressive HIV
      disease, whereas effective antiretroviral therapy results in its recovery.
      Observations of impaired IL-7 activity in HIV(+) individuals have suggested that
      CD127 has an important role in HIV immunopathogenesis. In addition, a soluble
      form of CD127 (sCD127) is upregulated in the plasma of HIV(+) individuals. Hence,
      CD127 is being increasingly considered as a marker of disease prognosis, and
      related information may provide insight into understanding the expression and
      role of other gamma(C) receptors in HIV disease and contribute to the development
      of novel cytokine-based therapeutics.

PMID- 21863002
TI  - Impact of weight and weight change on normalization of prediabetes and on
      persistence of normal glucose tolerance in an older population: the KORA S4/F4
      study.
AB  - BACKGROUND AND AIMS: In a population-based cohort study with older subjects and
      without specific interventions, we investigated the impact of body mass index
      (BMI) and BMI change (as well as waist circumference and change of waist
      circumference) on reversion from prediabetes to normal glucose tolerance (NGT)
      and on long-term persistence of NGT. MATERIALS AND METHODS: Oral glucose
      tolerance tests were conducted at baseline and at follow-up in a cohort study in
      Southern Germany (KORA S4/F4; 1223 subjects without diabetes aged 55-74 years at
      baseline in 1999-2001; 887 subjects (73%), of whom 436 had prediabetes at
      baseline, participated in the follow-up 7 years later). RESULTS: BMI reduction,
      but not initial BMI, predicted reversion from prediabetes to NGT. The odds ratio
      (OR) for returning to NGT was 1.43 (95% CI: 1.18-1.73) for a BMI decrease of 1 kg
      m(-2), after adjustment for age, sex, baseline glucose values and lifestyle
      factors. Initial BMI had no effect on reversion to NGT (OR=0.98, 95% CI: 0.91
      1.06, per kg m(-2)). Persistence of NGT was associated with baseline BMI
      (OR=0.94, 95% CI: 0.88-0.998) and BMI reduction (OR=1.16, 95% CI: 1.02-1.33, per
      decrease by 1 kg m(-2)). For waist circumference and change of waist
      circumference similar results were obtained. CONCLUSION: In older adults, weight
      loss strongly increased the chances of returning from prediabetes to NGT
      irrespective of initial BMI. Long-term persistence of NGT depended both on
      initial BMI and on BMI change.

PMID- 21863003
TI  - Adipokines and body fat composition in South Asians: results of the Metabolic
      Syndrome and Atherosclerosis in South Asians Living in America (MASALA) study.
AB  - OBJECTIVE: To investigate whether leptin and adiponectin are associated with body
      fat composition in a South Asian population independent of metabolic variables.
      DESIGN: Cross-sectional study. SUBJECTS: 150 South Asian men and women, between
      the ages of 45-79 years, in the San Francisco Bay Area without pre-existing
      clinical cardiovascular disease. MEASUREMENTS: Blood samples were obtained to
      measure glucose metabolism variables, lipid profiles and adipokines. Total body
      fat was determined using dual-energy X-ray absorptiometry. Abdominal computed
      tomography was used to measure subcutaneous, visceral and hepatic fat. RESULTS:
      Average body mass index (BMI) was overweight at 26.1+/-4.6 kg m(-2) and did not
      differ by sex. However, women had significantly more total body fat (P<0.001) and
      subcutaneous fat (P<0.001) than men, whereas men had significantly more visceral
      fat (P<0.001) and hepatic fat (P=0.04) than women. Women had significantly higher
      levels of adiponectin (P<0.01) and leptin (P<0.01). In sex-stratified analyses,
      leptin was strongly associated with all-body composition measures in women
      (P<0.05) as well as in men (P<0.05 except for hepatic fat), whereas there was an
      insignificant trend towards an inverse association between adiponectin and body
      composition in both women and men, which was significant in combined bivariate
      analyses. In multivariate analyses, leptin was strongly associated with all
      measures of adiposity, including BMI (P<0.001), total body fat (P<0.001),
      visceral fat (P<0.001) and hepatic fat (P=0.01). However, adiponectin's inverse
      association with adiposity was significantly attenuated by high-density
      lipoprotein (HDL), triglycerides and insulin resistance. The association between
      adipokines and diabetes was markedly attenuated after adjusting for body
      composition. CONCLUSION: Despite only modestly elevated BMI, South Asians have
      elevated levels of total and regional adiposity. Leptin is strongly associated
      with adiposity, whereas adiponectin's association with adiposity is attenuated by
      metabolic variables in South Asians. Adipokines in association with adiposity
      have an important role in the development of diabetes.

PMID- 21863004
TI  - Children's taste perception and cognitive development.

PMID- 21863005
TI  - Metabolic and genetic predictors of circulating adipocyte fatty acid-binding
      protein.
AB  - BACKGROUND: Adipocyte fatty acid-binding protein (AFABP) was recently introduced
      as a novel adipokine playing an important role in glucose homeostasis. In this
      study, we investigated the relationship between serum AFABP levels and metabolic,
      as well as cardiovascular parameters, in the self-contained population of Sorbs.
      Furthermore, we conducted a genome-wide association study on serum AFABP
      concentrations in the Sorbs and we separately analyzed the effects of two common
      variants in the FABP4 gene on AFABP serum concentration. METHODS: Serum AFABP
      concentrations were quantified by enzyme-linked immunosorbent assay and
      correlated with metabolic and cardiovascular parameters, as well as inflammatory
      markers and renal function, in 868 well-characterized non-diabetic Sorbs from
      Germany. RESULTS: Median AFABP serum concentrations were 1.5-fold higher in
      female subjects (23.03 MUg l(-1)) as compared to male subjects (15.86 MUg l(-1)).
      Waist-to-height ratio and glomerular filtration rate were independently
      associated with AFABP concentrations in multiple regression analysis in both
      female and male subjects. The genome-wide scan for association of single
      nucleotide polymorphisms with serum AFABP levels in the Sorbs revealed 39 loci
      reaching P-values <10(-4). Two single-nucleotide polymorphisms, rs16909187 and
      rs10808846, representing common genetic variation in FABP4 did not show any
      effect on serum AFABP concentrations in our study cohort. CONCLUSION: AFABP serum
      concentrations are determined by parameters of fat distribution, renal function
      and gender.

PMID- 21863006
TI  - Freely orbiting magnetic tweezers to directly monitor changes in the twist of
      nucleic acids.
AB  - The double-stranded nature of DNA links its replication, transcription and repair
      to rotational motion and torsional strain. Magnetic tweezers (MT) are a powerful
      single-molecule technique to apply both forces and torques to individual DNA or
      RNA molecules. However, conventional MT do not track rotational motion directly
      and constrain the free rotation of the nucleic acid tether. Here we present
      freely orbiting MT (FOMT) that allow the measurement of equilibrium fluctuations
      and changes in the twist of tethered nucleic acid molecules. Using a precisely
      aligned vertically oriented magnetic field, FOMT enable tracking of the rotation
      angle from straight forward (x,y)-position tracking and permits the application
      of calibrated stretching forces, without biasing the tether's free rotation. We
      utilize FOMT to measure the force-dependent torsional stiffness of DNA from
      equilibrium rotational fluctuations and to follow the assembly of recombination
      protein A filaments on DNA.

PMID- 21863008
TI  - Active sampling and decision making in Drosophila chemotaxis.
AB  - The ability to respond to chemical stimuli is fundamental to the survival of
      motile organisms, but the strategies underlying odour tracking remain poorly
      understood. Here we show that chemotaxis in Drosophila melanogaster larvae is an
      active sampling process analogous to sniffing in vertebrates. Combining computer
      vision algorithms with reconstructed olfactory environments, we establish that
      larvae orient in odour gradients through a sequential organization of
      stereotypical behaviours, including runs, stops, lateral head casts and directed
      turns. Negative gradients, integrated during runs, control the timing of turns.
      Positive gradients detected through high-amplitude head casts determine the
      direction of individual turns. By genetically manipulating the peripheral
      olfactory circuit, we examine how orientation adapts to losses and gains of
      function in olfactory input. Our findings suggest that larval chemotaxis
      represents an intermediate navigation strategy between the biased random walks of
      Escherichia Coli and the stereo-olfaction observed in rats and humans.

PMID- 21863007
TI  - Parkinson's disease induced pluripotent stem cells with triplication of the alpha
      synuclein locus.
AB  - A major barrier to research on Parkinson's disease is inaccessibility of diseased
      tissue for study. One solution is to derive induced pluripotent stem cells from
      patients and differentiate them into neurons affected by disease. Triplication of
      SNCA, encoding alpha-synuclein, causes a fully penetrant, aggressive form of
      Parkinson's disease with dementia. alpha-Synuclein dysfunction is the critical
      pathogenic event in Parkinson's disease, multiple system atrophy and dementia
      with Lewy bodies. Here we produce multiple induced pluripotent stem cell lines
      from an SNCA triplication patient and an unaffected first-degree relative. When
      these cells are differentiated into midbrain dopaminergic neurons, those from the
      patient produce double the amount of alpha-synuclein protein as neurons from the
      unaffected relative, precisely recapitulating the cause of Parkinson's disease in
      these individuals. This model represents a new experimental system to identify
      compounds that reduce levels of alpha-synuclein, and to investigate the
      mechanistic basis of neurodegeneration caused by alpha-synuclein dysfunction.

PMID- 21863009
TI  - A stem-group cnidarian described from the mid-Cambrian of China and its
      significance for cnidarian evolution.
AB  - Palaeontological data of extinct groups often sheds light on the evolutionary
      sequences leading to extant groups, but has failed to resolve the basal metazoan
      phylogeny including the origin of the Cnidaria. Here we report the occurrence of
      a stem-group cnidarian, Cambroctoconus orientalis gen. et sp. nov., from the mid
      Cambrian of China, which is a colonial organism with calcareous octagonal conical
      cup-shaped skeletons. It bears cnidarian features including longitudinal septa
      arranged in octoradial symmetry and colonial occurrence, but lacks a jelly-like
      mesenchyme. Such morphological characteristics suggest that the colonial
      occurrence with polyps of octoradial symmetry is the plesiomorphic condition of
      the Cnidaria and appeared earlier than the jelly-like mesenchyme during the
      course of evolution.

PMID- 21863011
TI  - Anatomically modern Carboniferous harvestmen demonstrate early cladogenesis and
      stasis in Opiliones.
AB  - Harvestmen, the third most-diverse arachnid order, are an ancient group found on
      all continental landmasses, except Antarctica. However, a terrestrial mode of
      life and leathery, poorly mineralized exoskeleton makes preservation unlikely,
      and their fossil record is limited. The few Palaeozoic species discovered to date
      appear surprisingly modern, but are too poorly preserved to allow unequivocal
      taxonomic placement. Here, we use high-resolution X-ray micro-tomography to
      describe two new harvestmen from the Carboniferous (~305 Myr) of France. The
      resulting computer models allow the first phylogenetic analysis of any Palaeozoic
      Opiliones, explicitly resolving both specimens as members of different extant
      lineages, and providing corroboration for molecular estimates of an early
      Palaeozoic radiation within the order. Furthermore, remarkable similarities
      between these fossils and extant harvestmen implies extensive morphological
      stasis in the order. Compared with other arachnids--and terrestrial arthropods
      generally--harvestmen are amongst the first groups to evolve fully modern body
      plans.

PMID- 21863012
TI  - Evidence of superdense aluminium synthesized by ultrafast microexplosion.
AB  - At extreme pressures and temperatures, such as those inside planets and stars,
      common materials form new dense phases with compacted atomic arrangements and
      unusual physical properties. The synthesis and study of new phases of matter at
      pressures above 100 GPa and temperatures above 10(4) K--warm dense matter--may
      reveal the functional details of planet and star interiors, and may lead to
      materials with extraordinary properties. Many phases have been predicted
      theoretically that may be realized once appropriate formation conditions are
      found. Here we report the synthesis of a superdense stable phase of body-centred
      cubic aluminium, predicted by first-principles theories to exist at pressures
      above 380 GPa. The superdense Al phase was synthesized in the non-equilibrium
      conditions of an ultrafast laser-induced microexplosion confined inside sapphire
      (alpha-Al(2)O(3)). Confined microexplosions offer a strategy to create and
      recover high-density polymorphs, and a simple method for tabletop study of warm
      dense matter.

PMID- 21863010
TI  - Mesozoic retroposons reveal parrots as the closest living relatives of passerine
      birds.
AB  - The relationships of passerines (such as the well-studied zebra finch) with non
      passerine birds is one of the great enigmas of avian phylogenetic research,
      because decades of extensive morphological and molecular studies yielded highly
      inconsistent results between and within data sets. Here we show the first
      application of the virtually homoplasy-free retroposon insertions to this
      controversy. Our study examined ~200,000 retroposon-containing loci from various
      avian genomes and retrieved 51 markers resolving early bird phylogeny. Among
      these, we obtained statistically significant evidence that parrots are the
      closest and falcons the second-closest relatives of passerines, together
      constituting the Psittacopasserae and the Eufalconimorphae, respectively. Our new
      and robust phylogenetic framework has substantial implications for the
      interpretation of various conclusions drawn from passerines as model organisms.
      This includes insights of relevance to human neuroscience, as vocal learning
      (that is, birdsong) probably evolved in the psittacopasseran ancestor, >30
      million years earlier than previously assumed.

PMID- 21863013
TI  - Direct visualization of microtubules using a genetic tool to analyse radial
      progenitor-astrocyte continuum in brain.
AB  - Microtubule cytoskeletal dynamics of cortical progenitors and astroglial cells
      have critical roles in the emergence of normal functional organization of
      cerebral cortex and in disease processes such as tumorigenesis. However, tools to
      efficiently visualize these events are lacking. Here we describe a mouse genetic
      model to efficiently visualize and analyse radial progenitors, their astroglial
      progeny, and the microtubule cytoskeleton of these cells in the developing and
      adult brain. Using this tool, we demonstrate altered microtubule organization and
      capture dynamics in adenomatous polyposis coli-deficient radial progenitors.
      Further, using multiphoton microscopy, we show the utility of this tool in real
      time imaging of astrocytes in living mouse brain and the short-term stable nature
      of astrocytes in cerebral cortex. Thus, this model will help explore the dynamics
      of radial progenitor/astrocyte development or dysfunction and the influence of
      microtubule functions during these events.

PMID- 21863014
TI  - Spatio-temporal focusing of an ultrafast pulse through a multiply scattering
      medium.
AB  - Pulses of light propagating through multiply scattering media undergo complex
      spatial and temporal distortions to form the familiar speckle pattern. There is
      much current interest in both the fundamental properties of speckles and the
      challenge of spatially and temporally refocusing behind scattering media. Here we
      report on the spatially and temporally resolved measurement of a speckle field
      produced by the propagation of an ultrafast optical pulse through a thick
      strongly scattering medium. By shaping the temporal profile of the pulse using a
      spectral phase filter, we demonstrate the spatially localized temporal
      recompression of the output speckle to the Fourier-limit duration, offering an
      optical analogue to time-reversal experiments in the acoustic regime. This
      approach shows that a multiply scattering medium can be put to profit for light
      manipulation at the femtosecond scale, and has a diverse range of potential
      applications that includes quantum control, biological imaging and photonics.

PMID- 21863015
TI  - Reverse electrowetting as a new approach to high-power energy harvesting.
AB  - Over the last decade electrical batteries have emerged as a critical bottleneck
      for portable electronics development. High-power mechanical energy harvesting can
      potentially provide a valuable alternative to the use of batteries, but, until
      now, a suitable mechanical-to-electrical energy conversion technology did not
      exist. Here we describe a novel mechanical-to-electrical energy conversion method
      based on the reverse electrowetting phenomenon. Electrical energy generation is
      achieved through the interaction of arrays of moving microscopic liquid droplets
      with novel nanometer-thick multilayer dielectric films. Advantages of this
      process include the production of high power densities, up to 10(3) W m(-2); the
      ability to directly utilize a very broad range of mechanical forces and
      displacements; and the ability to directly output a broad range of currents and
      voltages, from several volts to tens of volts. These advantages make this method
      uniquely suited for high-power energy harvesting from a wide variety of
      environmental mechanical energy sources.

PMID- 21863016
TI  - Nanomechanical DNA origami 'single-molecule beacons' directly imaged by atomic
      force microscopy.
AB  - DNA origami involves the folding of long single-stranded DNA into designed
      structures with the aid of short staple strands; such structures may enable the
      development of useful nanomechanical DNA devices. Here we develop versatile
      sensing systems for a variety of chemical and biological targets at molecular
      resolution. We have designed functional nanomechanical DNA origami devices that
      can be used as 'single-molecule beacons', and function as pinching devices. Using
      'DNA origami pliers' and 'DNA origami forceps', which consist of two levers ~170
      nm long connected at a fulcrum, various single-molecule inorganic and organic
      targets ranging from metal ions to proteins can be visually detected using atomic
      force microscopy by a shape transition of the origami devices. Any detection
      mechanism suitable for the target of interest, pinching, zipping or unzipping,
      can be chosen and used orthogonally with differently shaped origami devices in
      the same mixture using a single platform.

PMID- 21863018
TI  - Bethe-hole polarization analyser for the magnetic vector of light.
AB  - The nature of light as an electromagnetic wave with transverse components has
      been confirmed using optical polarizers, which are sensitive to the orientation
      of the electric field. Recent advances in nanoscale optical technologies demand
      their magnetic counterpart, which can sense the orientation of the optical
      magnetic field. Here we report that subwavelength metallic apertures on infinite
      plane predominantly sense the magnetic field of light, establishing the
      orientation of the magnetic component of light as a separate entity from its
      electric counterpart. A subwavelength aperture combined with a tapered optical
      fibre probe can also serve as a nanoscale polarization analyser for the optical
      magnetic field, analogous to a nanoparticle sensing the local electric
      polarization. As proof of its functionality, we demonstrate the measurement of a
      magnetic field orientation that is parallel to the electric field, as well as a
      circularly polarized magnetic field in the presence of a linearly polarized
      electric field.

PMID- 21863017
TI  - Discovery of lost diversity of paternal horse lineages using ancient DNA.
AB  - Modern domestic horses display abundant genetic diversity within female-inherited
      mitochondrial DNA, but practically no sequence diversity on the male-inherited Y
      chromosome. Several hypotheses have been proposed to explain this discrepancy,
      but can only be tested through knowledge of the diversity in both the ancestral
      (pre-domestication) maternal and paternal lineages. As wild horses are
      practically extinct, ancient DNA studies offer the only means to assess this
      ancestral diversity. Here we show considerable ancestral diversity in ancient
      male horses by sequencing 4 kb of Y chromosomal DNA from eight ancient wild
      horses and one 2,800-year-old domesticated horse. Both ancient and modern
      domestic horses form a separate branch from the ancient wild horses, with the
      Przewalski horse at its base. Our methodology establishes the feasibility of re
      sequencing long ancient nuclear DNA fragments and demonstrates the power of
      ancient Y chromosome DNA sequence data to provide insights into the evolutionary
      history of populations.

PMID- 21863019
TI  - A systematic analysis of Drosophila TUDOR domain-containing proteins identifies
      Vreteno and the Tdrd12 family as essential primary piRNA pathway factors.
AB  - PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) form the core of a
      gonad-specific small RNA silencing pathway that protects the animal genome
      against the deleterious activity of transposable elements. Recent studies linked
      the piRNA pathway to TUDOR biology as TUDOR domains of various proteins bind
      symmetrically methylated Arginine residues in PIWI proteins. We systematically
      analysed the Drosophila TUDOR protein family and identified four previously not
      characterized TUDOR domain-containing proteins (CG4771, CG14303, CG11133 and
      CG31755) as essential piRNA pathway factors. We characterized CG4771 (Vreteno) in
      detail and demonstrate a critical role for this protein in primary piRNA
      biogenesis. Vreteno physically and/or genetically interacts with the primary
      pathway components Piwi, Armitage, Yb and Zucchini. Vreteno also interacts with
      the Tdrd12 orthologues CG11133 (Brother of Yb) and CG31755 (Sister of Yb), which
      are essential for the primary piRNA pathway in the germline and probably replace
      the function of the related but soma-specific factor Yb.

PMID- 21863022
TI  - Campaign awareness and oral cancer knowledge in UK resident adult Bangladeshi: a
      cross-sectional study.
AB  - BACKGROUND: This study reports awareness of the 'Open up to Mouth Cancer'
      campaign materials and oral cancer knowledge among two UK adult Bangladeshi
      communities, both at high risk for oral cancer. METHODS: Differences in the
      outcomes of campaign awareness and knowledge of oral cancer risk factors and
      early signs were compared between campaign and comparison areas. Home-based
      interviews were conducted with representative samples from both areas by
      bilingual interviewers. Data collected included a modified 36-item Humphris Oral
      Cancer Knowledge Scale and socio-demographic information. The data were collected
      4 weeks after the campaign completion and analysed using chi(2)-tests and binary
      logistic regressions. RESULTS: The response rate was 77%. Both awareness of the
      campaign materials (29.99% (95% confidence interval (CI) 15.82, 46.99) vs 8.12%
      (95% CI 6.16, 10.62)) and the mean Humphris Oral Cancer Knowledge Scale scores
      (13.32 (95% CI 11.06, 15.57) vs 8.27 (95% CI 6.59, 9.94)) were higher in the
      campaign area. The campaign area sample was significantly more likely to be aware
      of the materials (odds ratio (OR)=6.03, 95% CI 3.00, 12.1). CONCLUSION: Superior
      awareness and oral cancer knowledge was identified in the community with access
      to the campaign materials. Further evaluation to identify long-term campaign
      impact is required.

PMID- 21863023
TI  - Upregulation of cancer-associated myofibroblasts by TGF-beta from scirrhous
      gastric carcinoma cells.
AB  - BACKGROUND: Myofibroblasts in the cancer microenvironment have recently been
      implicated in tumour growth and metastasis of gastric cancer. However, the
      mechanisms responsible for the regulation of myofibroblasts in cancer-associated
      fibroblasts (CAFs) remain unclear. This study was performed to clarify the
      mechanisms for regulation of myofibroblasts in gastric cancer microenvironment.
      METHODS: Two CAFs (CaF-29 and CaF-33) from the tumoural gastric wall and a normal
      fibroblast (NF-29) from the nontumoural gastric wall, 4 human gastric cancer cell
      lines from scirrhous gastric cancer (OCUM-2MD3 and OCUM-12), and non-scirrhous
      gastric cancer (MKN-45 and MKN-74) were used. Immunofluorescence microscopy by
      triple-immunofluorescence labelling (alpha-SMA, vimentin, and DAPI) was performed
      to determine the presence of alpha-SMA-positive myofibroblasts. Real-time RT-PCR
      was performed to examine alpha-SMA mRNA expression. RESULTS: Immunofluorescence
      microscopy showed that the frequency of myofibroblasts in CaF-29 was greater than
      that in NF-29. The number of myofibroblasts in gastric fibroblasts gradually
      decreased with serial passages. Transforming growth factor-beta (TGF-beta)
      significantly increased the alpha-SMA expression level of CAFs. Conditioned
      medium from OCUM-2MD3 or OCUM-12 cells upregulated the alpha-SMA expression level
      of CAFs, but that from MKN-45 or MKN-74 cells did not. The alpha-SMA upregulation
      effect of conditioned medium from OCUM-2MD3 or OCUM-12 cells was significantly
      decreased by an anti-TGF-beta antibody or Smad2 siRNA. CONCLUSION: Transforming
      growth factor-beta from scirrhous gastric carcinoma cells upregulates the number
      of myofibroblasts in CAFs.

PMID- 21863020
TI  - Deciphering the rules of programmed cell death to improve therapy of cancer and
      other diseases.
AB  - Apoptosis, the major form of programmed cell death in metazoan organisms, plays
      critical roles in normal development, tissue homeostasis and immunity, and its
      disturbed regulation contributes to many pathological states, including cancer,
      autoimmunity, infection and degenerative disorders. In vertebrates, it can be
      triggered either by engagement of 'death receptors' of the tumour necrosis factor
      receptor family on the cell surface or by diverse intracellular signals that act
      upon the Bcl-2 protein family, which controls the integrity of the mitochondrial
      outer membrane through the complex interactions of family members. Both pathways
      lead to cellular demolition by dedicated proteases termed caspases. This review
      discusses the groundbreaking experiments from many laboratories that have
      clarified cell death regulation and galvanised efforts to translate this
      knowledge into novel therapeutic strategies for the treatment of malignant and
      perhaps certain autoimmune and infectious diseases.

PMID- 21863024
TI  - Lung cancer incidence and survival in different ethnic groups in South East
      England.
AB  - BACKGROUND: This study aimed to examine the incidence and survival of lung cancer
      patients from several different ethnic groups in a large ethnically diverse
      population in the United Kingdom. METHODS: Data on residents of South East
      England diagnosed with lung cancer between 1998 and 2003 were extracted from the
      Thames Cancer Registry database. Age- and socioeconomic deprivation-standardised
      incidence rate ratios were calculated for males and females in each ethnic group.
      Overall survival was examined using Cox regression, adjusted for age,
      socioeconomic deprivation, stage of disease and treatment. Results are presented
      for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and
      Chinese patients, apart from female survival results where only the White, South
      Asian and Black ethnic groups were analysed. RESULTS: Compared with other ethnic
      groups of the same sex, Bangladeshi men, White men and White women had the
      highest incidence rates. Bangladeshi men had consistently higher survival
      estimates compared with White men (fully adjusted hazard ratio 0.46; P<0.001).
      Indian (0.84; P=0.048), Black Caribbean (0.87; P=0.47) and Black African (0.68;
      P=0.007) men also had higher survival estimates. South Asian (0.73; P=0.006) and
      Black (0.74; P=0.004) women had higher survival than White women. CONCLUSION:
      Smoking prevention messages need to be targeted for different ethnic groups to
      ensure no groups are excluded. The apparent better survival of South Asian and
      Black patients is surprising, and more detailed follow-up studies are needed to
      verify these results.

PMID- 21863026
TI  - Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic
      acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro.
AB  - BACKGROUND: T-cell responses contribute to the anti-tumoural effect of
      photodynamic therapy (PDT). For such responses to occur, dendritic cells (DCs)
      have to migrate to the tumour, take up tumour antigens and respond to danger
      signals with maturation, before they engage in T-cell activation. Here, we have
      studied the effect of 5-aminolevulinic acid (ALA)-mediated PDT on DCs in vitro in
      a human spheroid model of glioblastoma (GB). METHODS: Spheroids of the GB cell
      lines U87 and U251 were treated with ALA/PDT, and effects on attraction, uptake
      of tumour antigens and maturation of DCs were studied. To block heat-shock
      protein-70 (HSP-70) on the spheroids, neutralising antibodies were used. RESULTS:
      5-Aminolevulinic acid /PDT-treated GB spheroids attracted DCs that acquired
      tumour antigens from the spheroids effectively. Moreover, co-culture with ALA/PDT
      treated spheroids induced DC maturation as indicated by the upregulation of CD83
      and co-stimulatory molecules as well as increased T-cell stimulatory activity of
      the DCs. Heat-shock protein-70 was upregulated on the spheroids after ALA/PDT
      treatment. Uptake of tumour antigens and DC maturation induced by the ALA/PDT
      treated spheroids were inhibited when HSP-70 was blocked. CONCLUSION: ALA/PDT
      treatment of glioma spheroids promotes the three initial steps of the afferent
      phase of adaptive immunity, which is at least partially mediated by HSP-70.

PMID- 21863025
TI  - Expression and functional role of CRIPTO-1 in cutaneous melanoma.
AB  - BACKGROUND: CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of
      human carcinoma of different histological origin. In this study we addressed the
      expression and the functional role of CR-1 in cutaneous melanoma. METHODS:
      Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by
      immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were
      evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated
      modified Boyden chambers. RESULTS: Expression of CR-1 protein and/or mRNA was
      found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21
      melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src
      and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased
      the invasive ability of melanoma cells that was prevented by treatment with
      either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530).
      Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive
      ability of melanoma cells. Finally, a close correlation was found in melanoma
      cells between the levels of expression of CR-1 and the effects of saracatinib on
      cell growth. CONCLUSION: These data indicate that a significant fraction of
      cutaneous melanoma expresses CR-1 and that this growth factor is involved in the
      invasion and proliferation of melanoma cells.

PMID- 21863027
TI  - miR-21 and miR-155 are associated with mitotic activity and lesion depth of
      borderline melanocytic lesions.
AB  - BACKGROUND: Expression of microRNAs (miRs) has been shown to be altered in many
      solid tumours and is being explored in melanoma. The malignant potential of some
      melanocytic lesions is difficult to predict. We hypothesised that
      characterisation of miR expression in borderline melanocytic proliferations would
      lead to the identification of a molecular profile that could be used with known
      prognostic factors to differentiate lesions with high malignant potential.
      METHODS: The miR expression profile of melanocytic lesions (benign naevi,
      malignant melanoma and borderline melanocytic tumours) was evaluated by real-time
      PCR. RESULTS: PCR analysis revealed primary cutaneous melanomas had an 8.6-fold
      overexpression of miR-21 and a 7.5-fold overexpression of miR-155 compared with
      benign naevi (P<0.0001). In situ hybridisation confirmed these results. miR-21
      and miR-155 were significantly overexpressed within borderline lesions (P=0.0011
      and P=0.0048, respectively). When borderline lesions were categorised by mitotic
      activity and Breslow thickness, miR-21 was associated with mitotic activity and
      miR-155 was associated with thickness (P<0.025). Among 14 patients with
      borderline lesions who underwent sentinel lymph node biopsy (SLNB), positive SLNB
      was associated with increased miR-21 and miR-155 in the primary lesion compared
      with lesions with a negative SLNB. CONCLUSION: MicroRNA expression profiles can
      be used to characterise atypical melanocytic lesions.

PMID- 21863028
TI  - Suitability of PSA-detected localised prostate cancers for focal therapy:
      experience from the ProtecT study.
AB  - BACKGROUND: Contemporary screening for prostate cancer frequently identifies
      small volume, low-grade lesions. Some clinicians have advocated focal prostatic
      ablation as an alternative to more aggressive interventions to manage these
      lesions. To identify which patients might benefit from focal ablative techniques,
      we analysed the surgical specimens of a large sample of population-detected men
      undergoing radical prostatectomy as part of a randomised clinical trial. METHODS:
      Surgical specimens from 525 men who underwent prostatectomy within the ProtecT
      study were analysed to determine tumour volume, location and grade. These
      findings were compared with information available in the biopsy specimen to
      examine whether focal therapy could be provided appropriately. RESULTS: Solitary
      cancers were found in prostatectomy specimens from 19% (100 out of 525) of men.
      In addition, 73 out of 425 (17%) men had multiple cancers with a solitary
      significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially
      suitable for focal therapy. The majority of these were small, well-differentiated
      lesions that appeared to be pathologically insignificant (38-66%). Criteria used
      to select patients for focal prostatic ablation underestimated the cancer's
      significance in 26% (34 out of 130) of men and resulted in overtreatment in more
      than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy,
      actually had significant solitary lesions. CONCLUSION: Focal therapy appears
      inappropriate for the majority of men presenting with prostate-specific antigen
      detected localised prostate cancer. Unifocal prostate cancers suitable for focal
      ablation are difficult to identify pre-operatively using biopsy alone. Most
      lesions meeting criteria for focal ablation were either more aggressive than
      expected or posed little threat of progression.

PMID- 21863029
TI  - Challenges of mediated communication, disclosure and patient autonomy in cross
      cultural cancer care.
AB  - BACKGROUND: Evidence concerning the influence of ethnic diversity on clinical
      encounters in cancer care is sparse. We explored health providers' experiences in
      this context. METHODS: Focus groups were conducted with a purposeful sample of
      106 health professionals of differing disciplines, in 18 UK primary and secondary
      care settings. Qualitative data were analysed using constant comparison and
      processes for validation. RESULTS: Communication and the quality of information
      exchanged with patients about cancer and their treatment was commonly frustrated
      within interpreter-mediated consultations, particularly those involving a family
      member. Relatives' approach to ownership of information and decision making could
      hinder assessment, informed consent and discussion of care with patients. This
      magnified the complexity of disclosing information sensitively and appropriately
      at the end of life. Professionals' concern to be patient-centred, and regard for
      patient choice and autonomy, were tested in these circumstances. CONCLUSION:
      Health professionals require better preparation to work effectively not only with
      trained interpreters, but also with the common reality of patients' families
      interpreting for patients, to improve quality of cancer care. Greater
      understanding of cultural and individual variations in concepts of disclosure,
      patient autonomy and patient-centredness is needed. The extent to which these
      concepts may be ethnocentric and lack universality deserves wider consideration.

PMID- 21863030
TI  - Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive
      advanced hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer
      deaths worldwide. We tested megestrol acetate (MA) against placebo in the
      treatment of advanced HCC. METHODS: From 2002 through 2007, this randomised
      double-blind trial enrolled 204 patients with treatment-naive advanced HCC
      (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from
      specialist care centres in six Asia-Pacific nations. Patients received placebo or
      MA (320 mg day(-1)). End points were overall survival (OS) and quality of life.
      RESULTS: An adverse but not statistically significant difference in OS was found
      for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio
      (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of
      good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both
      treatment groups, with the adverse effect of MA confined to those of poor status.
      Megestrol acetate patients had a worse global health status (not statistically
      significant) but reduced levels of appetite loss and nausea/vomiting. CONCLUSION:
      Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC.
      Overall survival with placebo differed markedly from that in similar trials
      conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on
      ECOG status and Child-Pugh score.

PMID- 21863031
TI  - Prediction of higher mortality reduction for the UK Breast Screening Frequency
      Trial: a model-based approach on screening intervals.
AB  - BACKGROUND: The optimal interval between two consecutive mammograms is uncertain.
      The UK Frequency Trial did not show a significant difference in breast cancer
      mortality between screening every year (study group) and screening every 3 years
      (control group). In this study, the trial is simulated in order to gain insight
      into the results of the trial and to predict the effect of different screening
      intervals on breast cancer mortality. METHODS: UK incidence, life tables and
      information from the trial were used in the microsimulation model MISCAN-Fadia to
      simulate the trial and predict the number of breast cancer deaths in each group.
      To be able to replicate the trial, a relatively low sensitivity had to be
      assumed. RESULTS: The model simulated a larger difference in tumour size
      distribution between the two groups than observed and a relative risk (RR) of
      0.83 of dying from breast cancer in the study group compared with the control
      group. The predicted RR is lower than that reported from the trial (RR 0.93), but
      within its 95% confidence interval (0.63-1.37). CONCLUSION: The present study
      suggests that there is benefit of shortening the screening interval, although the
      benefit is probably not large enough to start annual screening.

PMID- 21863032
TI  - Stabilisation of p53 enhances reovirus-induced apoptosis and virus spread through
      p53-dependent NF-kappaB activation.
AB  - BACKGROUND: Naturally oncolytic reovirus preferentially kills cancer cells,
      making it a promising cancer therapeutic. Mutations in tumour suppressor p53 are
      prevalent in cancers, yet the role of p53 in reovirus oncolysis is relatively
      unexplored. METHODS: Human cancer cell lines were exposed to Nutlin-3a, reovirus
      or a combination of the two and cells were processed for reovirus titration,
      western blot, real-time PCR and apoptosis assay using Annexin V and 7-AAD
      staining. Confocal microscopy was used to determine translocation of the NF
      kappaB p65 subunit. RESULTS: We show that despite similar reovirus replication in
      p53(+/+) and p53(-/-) cells, stabilisation of p53 by Nutlin-3a significantly
      enhanced reovirus-induced apoptosis and hence virus release and dissemination
      while having no direct effect on virus replication. Enhanced apoptosis by Nutlin
      3a was not observed in p53(-/-) or p53 knockdown cells; however, increased
      expression of Bax and p21 are required. Moreover, elevated NF-kappaB activation
      in reovirus-infected cells following Nutlin-3a treatment was necessary for
      enhanced reovirus-induced apoptosis, as synergistic cytotoxicity was overcome by
      specific NF-kappaB inhibitors. CONCLUSION: Nutlin-3a treatment enhances reovirus
      induced apoptosis and virus spread through p53-dependent NF-kappaB activation,
      and combination of reovirus and Nutlin-3a might represent an improved therapy
      against cancers harbouring wild-type p53.

PMID- 21863034
TI  - Developments in the management of febrile neutropenia.

PMID- 21863035
TI  - New tricks with old dogs: personalised medicine and clinical trials.
AB  - We provide a didactic example of how clinical trials can accommodate
      individualised patient information relative to design and analysis.

PMID- 21863033
TI  - A truncated form of CD9-partner 1 (CD9P-1), GS-168AT2, potently inhibits in vivo
      tumour-induced angiogenesis and tumour growth.
AB  - BACKGROUND: Tetraspanins are transmembrane proteins known to contribute to
      angiogenesis. CD9 partner-1 (CD9P-1/EWI-F), a glycosylated type 1 transmembrane
      immunoglobulin, is a member of the tetraspanin web, but its role in angiogenesis
      remains to be elucidated. METHODS: We measured the expression of CD9P-1 under
      angiogenic and angiostatic conditions, and the influence of its knockdown onto
      capillary structures formation by human endothelial cells (hECs). A truncated
      form of CDP-1, GS-168AT2, was produced and challenged vs hEC proliferation,
      migration and capillaries' formation. Its association with CD9P-1, CD9, CD81 and
      CD151 and the expressions of these later at hEC surface were analysed. Finally,
      its effects onto in vivo tumour-induced angiogenesis and tumour growth were
      investigated. RESULTS: Vascular endothelial growth factor (VEGF)-induced
      capillary tube-like formation was inhibited by tumour necrosis factor alpha and
      was associated with a rise in CD9P-1 mRNA expression (P<0.05); accordingly,
      knockdown of CD9P-1 inhibited VEGF-dependent in vitro angiogenesis. GS-168AT2
      dose-dependently inhibited in vitro angiogenesis, hEC migration and proliferation
      (P<0.05). Co-precipitation experiments suggest that GS-168AT2 corresponds to the
      sequence by which CD9P-1 physiologically associates with CD81. GS-168AT2 induced
      the depletion of CD151, CD9 and CD9P-1 from hEC surface, correlating with GS
      168AT2 degradation. Finally, in vivo injections of GS-168AT2 inhibited tumour
      associated angiogenesis by 53.4+/-9.5% (P=0.03), and reduced tumour growth of
      Calu 6 tumour xenografts by 73.9+/-16.4% (P=0.007) without bodyweight loss.
      CONCLUSION: The truncated form of CD9P-1, GS-168AT2, potently inhibits
      angiogenesis and cell migration by at least the downregulation of CD151 and CD9,
      which provides the first evidences for the central role of CD9P-1 in tumour
      associated angiogenesis and tumour growth.

PMID- 21863036
TI  - Correlation of the antimicrobial activity of ME1036 with its binding affinities
      to the penicillin-binding proteins from Streptococcus pneumoniae strains.
AB  - We have correlated the binding affinities of ME1036, a carbapenem, to the
      penicillin-binding proteins (PBPs) from Streptococcus pneumoniae strains, with
      its bactericidal potency against those same strains. Certain mutations in the
      PBPs from S. pneumonaie strains decrease the binding affinities of beta-lactams
      for PBPs, which gives rise to clinical resistance to those beta-lactams. ME1036
      has been shown to be strongly active against genotypic penicillin-intermediate S.
      pneumoniae (gPISP) strains and genotypic penicillin-resistant S. pneumoniae
      (gPRSP) strains that contain more than one mutation in their PBPs, owing to its
      strong affinity for those PBPs.

PMID- 21863037
TI  - SUMO2/3 conjugation is an endogenous neuroprotective mechanism.
AB  - Small ubiquitin-like modifier (SUMO)2/3 but not SUMO1 conjugation is activated
      after transient cerebral ischemia. To investigate its function, we blocked
      neuronal SUMO2/3 translation through lentiviral microRNA delivery in primary
      cortical neurons. Viability was unaffected by SUMO2/3 silencing unless neurons
      were stressed by transient oxygen-glucose deprivation (OGD). Both 15 and 45
      minutes of OGD were tolerated by control microRNA-expressing neurons but damaged
      >60% of neurons expressing SUMO2/3 microRNA. Damaging OGD (75 minutes) increased
      neuronal loss to 54% (control microRNA) and to 99% (SUMO2/3 microRNA). This
      suggests that activation of SUMO2/3 conjugation is an endogenous neuroprotective
      stress response.

PMID- 21863038
TI  - Cerebral oxygen metabolism of rats using injectable (15)O-oxygen with a steady
      state method.
AB  - To develop a less-stressful and simple method for measurement of the cerebral
      metabolic rate of oxygen (CMRO(2)) in small animals, the steady-state method was
      applied to injectable (15)O(2)-PET ((15)O(2)-positron emission tomography) using
      hemoglobin-containing vesicles ((15)O(2)-HbV). Ten normal rats and 10 with middle
      cerebral arterial occlusion (MCAO) were studied using a small animal PET scanner.
      A series of (15)O-PET scans with C(15)O-labeled HbV, H(2)(15)O, and (15)O(2)-HbV
      were performed with 10 to 15 minutes intervals to measure cerebral blood volume
      (CBV), cerebral blood flow (CBF), and CMRO(2). Positron emission tomography scans
      were started with a tracer injection using a multiprogramming syringe pump, which
      provides a slowly increasing injection volume to achieve steady-state
      radioactivity for H(2)(15)O and (15)O(2)-HbV scans. The radioactivity
      concentration of (15)O rapidly achieved equilibrium in the blood and whole brain
      at about 2 minutes after H(2)(15)O and (15)O(2)-HbV administration, which was
      stable during the scans. The whole brain mean values of CBF, CBV, and CMRO(2)
      were 54.3+/-2.0 mL per 100 g per minute, 4.9+/-0.4 mL/100 g, and 2.8+/-0.2 MUmoL
      per g per minute (6.2+/-0.4 mL per 100 g per minute) in the normal rats,
      respectively. In the MCAO model rats, all hemodynamic parameters of the
      infarction area on the occlusion side significantly decreased. The steady-state
      method with (15)O-labeled HbV is simple and useful to analyze hemodynamic changes
      in studies with model animals.

PMID- 21863039
TI  - Low frequency stimulation of the perforant pathway generates anesthesia-specific
      variations in neural activity and BOLD responses in the rat dentate gyrus.
AB  - To study how various anesthetics affect the relationship between stimulus
      frequency and generated functional magnetic resonance imaging (fMRI) signals in
      the rat dentate gyrus, the perforant pathway was electrically stimulated with
      repetitive low frequency (i.e., 0.625, 1.25, 2.5, 5, and 10 Hz) stimulation
      trains under isoflurane/N(2)O, isoflurane, medetomidine, and alpha-chloralose.
      During stimulation, the blood oxygen level-dependent signal intensity (BOLD
      response) and local field potentials in the dentate gyrus were simultaneously
      recorded to prove whether the present anesthetic controls the generation of a
      BOLD response via targeting general hemodynamic parameters, by affecting
      mechanisms of neurovascular coupling, or by disrupting local signal processing.
      Using this combined electrophysiological/fMRI approach, we found that the
      threshold frequency (i.e., the minimal frequency required to trigger significant
      BOLD responses), the optimal frequency (i.e., the frequency that elicit the
      strongest BOLD response), and the spatial distribution of generated BOLD
      responses are specific for each anesthetic used. Concurrent with anesthetic
      dependent characteristics of the BOLD response, we found the pattern of stimulus
      induced neuronal activity in the dentate gyrus is also specific for each
      anesthetic. Consequently, the anesthetic-specific influence on local signaling
      processes is the underlying cause for the observation that an identical stimulus
      elicits different BOLD responses under various anesthetics.

PMID- 21863041
TI  - Cross-sectional and longitudinal association between homocysteine, vitamin B12
      and physical performance in older persons.
AB  - BACKGROUND/OBJECTIVES: Decreases in physical performance are associated with
      multiple negative health outcomes. The objective of this study was to examine
      whether high plasma homocysteine and low serum vitamin B12 are independent risk
      factors for lower physical performance, both cross-sectionally and
      longitudinally. SUBJECTS/METHODS: This study was performed in persons aged >=65
      years of the LASA (Longitudinal Aging Study Amsterdam), an ongoing cohort study.
      Blood was collected in 1995/1996 (n=1352). Physical performance was assessed in
      1995/1996 and in 1998/1999 using three tests: the walking test, the chair stands
      test and the tandem stand (n=901-1155). RESULTS: After adjustment for
      confounding, women in the highest quartile of homocysteine had a significantly
      lower physical performance than did those in the lowest quartile in the cross
      sectional analyses (beta=-0.93, s.e.=0.34, P<0.01). This association was
      borderline statistically significant in the longitudinal analyses (beta=-0.69,
      s.e.=0.35, P=0.05). After additional adjustment for serum vitamin B12, both
      associations were statistically significant (P<0.05). For vitamin B12 in women,
      and for homocysteine and vitamin B12 in men, the observed associations were less
      consistent. CONCLUSIONS: High plasma homocysteine is an independent risk factor
      for lower physical performance in older women. The association between vitamin
      B12 and physical performance is less clear.

PMID- 21863042
TI  - Implementation of nutritional guidelines in a university hospital monitored by
      repeated point prevalence surveys.
AB  - BACKGROUND/OBJECTIVES: Malnutrition is present in 20-50% of hospitalized
      patients, and nutritional care is a challenge. The aim was to evaluate whether
      the implementation of a nutritional strategy would influence nutritional care
      performance in a university hospital. SUBJECTS/METHODS: This was a prospective
      quality improvement program implementing guidelines for nutritional care, with
      the aim of improving nutritional practice. The Nutrition Risk Screening (NRS)
      2002 was used. Point prevalence surveys over 2 years to determine whether
      nutritional practice had improved. RESULTS: In total, 3604 (70%) of 5183 eligible
      patients were screened and 1230 (34%) were at nutritional risk. Only 53% of the
      at-risk patients got nutritional treatment and 5% were seen by a dietician. The
      proportion of patients screened increased from the first to the eighth point
      prevalence survey (P=0.012), but not the proportion of patients treated (P=0.66).
      The four initial screening questions in NRS 2002 identified 92% of the patients
      not at nutritional risk. CONCLUSIONS: Implementation of nutritional guidelines
      improved the screening performance, but did not increase the proportion of
      patients who received nutritional treatment. Point prevalence surveys were useful
      to evaluate nutritional practice in this university hospital. In order to improve
      practice, we suggest using only the four initial screening questions in NRS 2002
      to identify patients not at risk, better education in nutritional care for
      physicians and nurses, and more dieticians employed. Audit of implementation of
      guidelines, performed by health authorities, and specific reimbursement for
      managing nutrition may also improve practice.

PMID- 21863040
TI  - Experimental intracerebral hemorrhage: avoiding pitfalls in translational
      research.
AB  - Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes,
      yet treatments are mainly limited to supportive management, and surgery remains
      controversial. Despite significant advances in our understanding of ICH
      pathophysiology, we still lack preclinical models that accurately replicate the
      underlying mechanisms of injury. Current experimental ICH models (including
      autologous blood and collagenase injection) simulate different aspects of ICH
      mediated injury but lack some features of the clinical condition. Newly developed
      models, notably hypertension- and oral anticoagulant therapy-associated ICH
      models, offer added benefits but further study is needed to fully validate them.
      Here, we describe and discuss current approaches to experimental ICH, with
      suggestions for changes in how this condition is studied in the laboratory.
      Although advances in imaging over the past few decades have allowed greater
      insight into clinical ICH, there remains an important role for experimental
      models in furthering our understanding of the basic pathophysiologic processes
      underlying ICH, provided limitations of animal models are borne in mind. Owing to
      differences in existing models and the failed translation of benefits in
      experimental ICH to clinical practice, putative neuroprotectants should be
      trialed in multiple models using both histological and functional outcomes until
      a more accurate model of ICH is developed.

PMID- 21863043
TI  - Spatial coding: does the brain know how high it is?

PMID- 21863044
TI  - Neurotrophic factors: ride back to the nucleus.

PMID- 21863045
TI  - Metabolism: flexible flux.

PMID- 21863048
TI  - Therapy: modifying MYC expression.

PMID- 21863049
TI  - Tumorigenesis: the origins of glioma.

PMID- 21863051
TI  - Could platelet-accumulating polyphenols prevent tumour metastasis?

PMID- 21863052
TI  - Microevolution of sympatry: landscape genetics of hedgehogs Erinaceus europaeus
      and E. roumanicus in Central Europe.
AB  - We used the mitochondrial control region and nuclear microsatellites to assess
      the distribution patterns, population structure, demography and landscape
      genetics for the hedgehogs Erinaceus europaeus and Erinaceus roumanicus in a
      transect of the mid-European zone of sympatry. E. roumanicus was less frequent
      and restricted to regions with lower altitudes. Demographic analyses suggested
      recent population growth in this species. A comparison of patterns in the spatial
      variability of mitochondrial and nuclear DNA indicated less sex-biased dispersal
      and higher levels of gene flow in E. roumanicus. No evidence of recent
      hybridisation or introgression was detected. We interpreted these results by
      comparing with phylogeographic and palaeontological studies as well as with the
      occurrence of hybridisation in the Russian contact zone. We propose that Central
      Europe was colonised by E. roumanicus by the beginning of the Neolithic period
      and that there was a subsequent reinforcement stage as well as the formation of a
      zone of sympatry after the complete reproductive isolation of both species.

PMID- 21863050
TI  - RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour
      suppression and oncogenesis.
AB  - The ubiquitin-proteasome system has numerous crucial roles in physiology and
      pathophysiology. Fundamental to the specificity of this system are ubiquitin
      protein ligases (E3s). Of these, the majority are RING finger and RING finger
      related E3s. Many RING finger E3s have roles in processes that are central to the
      maintenance of genomic integrity and cellular homeostasis, such as the anaphase
      promoting complex/cyclosome (APC/C), the SKP1-cullin 1-F-box protein (SCF) E3s,
      MDM2, BRCA1, Fanconi anaemia proteins, CBL proteins, von Hippel-Lindau tumour
      suppressor (VHL) and SIAH proteins. As a result, many RING finger E3s are
      implicated in either the suppression or the progression of cancer. This Review
      summarizes current knowledge in this area.

PMID- 21863053
TI  - C1q enhances cone photoreceptor survival in a mouse model of autosomal recessive
      retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a degenerative retinal disease involving progressive
      loss of rod and cone photoreceptor function. It represents the most common form
      of registered blindness among the working aged populations of developed
      countries. Given the immense genetic heterogeneity associated with this disease,
      parameters influencing cone photoreceptor survival (preservation of daytime
      vision) that are independent of primary mutations are exceedingly important to
      identify from a therapeutic standpoint. Here we identify C1q, the primary
      component of the classical complement pathway, as a cone photoreceptor neuronal
      survival factor.

PMID- 21863054
TI  - Beckwith-Wiedemann syndrome caused by maternally inherited mutation of an OCT
      binding motif in the IGF2/H19-imprinting control region, ICR1.
AB  - The imprinted expression of the IGF2 and H19 genes is controlled by the
      imprinting control region 1 (ICR1) located at chromosome 11p15.5. DNA methylation
      defects involving ICR1 result in two growth disorders with opposite phenotypes:
      an overgrowth disorder, the Beckwith-Wiedemann syndrome (maternal ICR1
      hypermethylation in 10% of BWS cases) and a growth retardation disorder, the
      Silver-Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases).
      In familial BWS, hypermethylation of ICR1 has been found in association with
      microdeletion of repetitive DNA motifs within ICR1 that bind the zinc finger
      protein CTCF; but more recently, ICR1 point mutations were described in BWS
      pedigrees. We present a case report of two brothers with BWS and prolonged post
      pubertal growth resulting in very large stature. A maternally inherited point
      mutation was identified in ICR1 in both brothers, which altered binding of OCT
      transcription factors. The same mutation was present on the paternally inherited
      allele of their unaffected mother. This is a second report of a point mutation
      causing ICR1 hypermethylation by altering an OCT-binding motif. The atypical
      growth phenotype of the brothers may be connected to the unusual underlying cause
      of their BWS.

PMID- 21863055
TI  - Clinical utility gene card for: Cystinuria.

PMID- 21863056
TI  - Clinical utility gene card for: mucopolysaccharidosis type II.

PMID- 21863057
TI  - Clinical utility gene card for: multiple endocrine neoplasia type 2.

PMID- 21863058
TI  - Brazilian urban population genetic structure reveals a high degree of admixture.
AB  - Advances in genotyping technologies have contributed to a better understanding of
      human population genetic structure and improved the analysis of association
      studies. To analyze patterns of human genetic variation in Brazil, we used SNP
      data from 1129 individuals--138 from the urban population of Sao Paulo, Brazil,
      and 991 from 11 populations of the HapMap Project. Principal components analysis
      was performed on the SNPs common to these populations, to identify the
      composition and the number of SNPs needed to capture the genetic variation of
      them. Both admixture and local ancestry inference were performed in individuals
      of the Brazilian sample. Individuals from the Brazilian sample fell between
      Europeans, Mexicans, and Africans. Brazilians are suggested to have the highest
      internal genetic variation of sampled populations. Our results indicate, as
      expected, that the Brazilian sample analyzed descend from Amerindians, African,
      and/or European ancestors, but intermarriage between individuals of different
      ethnic origin had an important role in generating the broad genetic variation
      observed in the present-day population. The data support the notion that the
      Brazilian population, due to its high degree of admixture, can provide a valuable
      resource for strategies aiming at using admixture as a tool for mapping complex
      traits in humans.

PMID- 21863059
TI  - No evidence for pathogenic variants or maternal effect of ZFP57 as the cause of
      Beckwith-Wiedemann Syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome, which, in 50-60% of
      sporadic cases, is caused by hypomethylation of KCNQ1OT1 differentially
      methylated region (DMR) at chromosome 11p15.5. The underlying defect of this
      hypomethylation is largely unknown. Recently, recessive mutations of the ZFP57
      gene were reported in patients with transient neonatal diabetes mellitus type 1,
      showing hypomethylation at multiple imprinted loci, including KCNQ1OT1 DMR in
      some. The aim of our study was to determine whether ZFP57 alterations were a
      genetic cause of the hypomethylation at KCNQ1OT1 DMR in patients with BWS. We
      sequenced ZFP57 in 27 BWS probands and in 23 available mothers to test for a
      maternal effect. We identified three novel, presumably benign sequence variants
      in ZFP57; thus, we found no evidence for ZFP57 alterations as a major cause in
      sporadic BWS cases.

PMID- 21863060
TI  - Regressed lymphatic vessels develop during corneal repair.
AB  - The fate of newly synthesized lymphatic vessels induced by inflammation is poorly
      understood. To address this question, we designed experiments to determine the
      morphologic, phenotypic, and functional differences in regressing lymphatic
      vessels in the context of corneal recovery after an inflammatory response. A
      suture removal modification was used to induce corneal recovery after suture
      induced inflammation. We identified an increase in markers of corneal
      inflammation in sutured cornea that resolved in 14 days after suture removal.
      Sprouting newly synthesized lymphatic vessels trafficking MHC-II-positive
      leukocytes were visualized in sutured cornea. Following suture removal and
      recovery, the visualized lymphatic vessels were thin and fragmented, had bulbous
      termini, discontinuous expression of CD31 and VE-cadherin, and excluded MHC-II
      positive leukocytes. VEGF-A, VEGF-C, and TGF-beta mRNA levels were increased
      during corneal recovery, suggesting a complex interaction between lymphangiogenic
      factors and the mechanisms that regulate corneal recovery. The balance of
      lymphatic vessel growth and regression is likely to have a central role in the
      pathogenesis of corneal inflammatory diseases.

PMID- 21863061
TI  - Downregulation of hemojuvelin prevents inhibitory effects of bone morphogenetic
      proteins on iron metabolism in hepatocellular carcinoma.
AB  - Recently, we revealed that bone morphogenetic protein (BMP) 4 is increased in
      hepatocellular carcinoma (HCC). Furthermore, latest reports described BMPs, in
      particular BMP6, as important regulators of hepcidin expression in iron
      homeostasis. Therefore, we aimed to unravel why enhanced BMP expression in HCC
      patients does not lead to severe changes in iron metabolism. Initial analysis of
      the BMP4 and BMP6 expression patterns revealed enhanced expression on mRNA and
      protein level in HCC cell lines and tissue samples compared with primary human
      hepatocytes (PHHs) and normal liver tissues. However and interestingly, hepcidin
      expression was reduced in HCC cell lines and tissues. Analysis of BMP6 receptor
      expression revealed loss of BMP6-specific receptor subunit in HCC. To identify a
      possible regulatory mechanism causing lack of reaction to BMP4 we analyzed the
      expression of hemojuvelin (HJV), which is involved in iron metabolism as BMP co
      receptor. HJV expression was markedly decreased in HCC cell lines and tissues.
      HJV promoter analysis revealed potential HNF-1alpha and snail-binding sites, but
      functional analysis ruled out that these transcriptional regulators or promoter
      methylation are the cause of HJV downregulation in HCC. However, we identified AU
      rich elements in the HJV 3'-untranslated region and revealed significantly faster
      decay of HJV mRNA in HCC cells as compared with PHH indicating decreased mRNA
      stability as the reason for the loss of HJV expression in HCC.

PMID- 21863062
TI  - Dual role of the mitochondrial protein frataxin in astrocytic tumors.
AB  - The mitochondrial protein frataxin (FXN) is known to be involved in mitochondrial
      iron homeostasis and iron-sulfur cluster biogenesis. It is discussed to modulate
      function of the electron transport chain and production of reactive oxygen
      species (ROS). FXN loss in neurons and heart muscle cells causes an autosomal
      dominant mitochondrial disorder, Friedreich's ataxia. Recently, tumor induction
      after targeted FXN deletion in liver and reversal of the tumorigenic phenotype of
      colonic carcinoma cells following FXN overexpression were described in the
      literature, suggesting a tumor suppressor function. We hypothesized that a
      partial reversal of the malignant phenotype of glioma cells should occur after
      FXN transfection, if the mitochondrial protein has tumor suppressor functions in
      these brain tumors. In astrocytic brain tumors and tumor cell lines, we observed
      reduced FXN levels compared with non-neoplastic astrocytes. Mitochondrial content
      (citrate synthase activity) was not significantly altered in U87MG glioblastoma
      cells stably overexpressing FXN (U87-FXN). Surprisingly, U87-FXN cells exhibited
      increased cytoplasmic ROS levels, although mitochondrial ROS release was
      attenuated by FXN, as expected. Higher cytoplasmic ROS levels corresponded to
      reduced activities of glutathione peroxidase and catalase, and lower glutathione
      content. The defect of antioxidative capacity resulted in increased
      susceptibility of U87-FXN cells against oxidative stress induced by H(2)O(2) or
      buthionine sulfoximine. These characteristics may explain a higher sensitivity
      toward staurosporine and alkylating drugs, at least in part. On the other hand,
      U87-FXN cells exhibited enhanced growth rates in vitro under growth factor
      restricted and hypoxic conditions and in vivo using tumor xenografts in nude
      mice. These data contrast to a general tumor suppressor function of FXN but
      suggest a dual, pro-proliferative but chemosensitizing role in astrocytic tumors.

PMID- 21863063
TI  - Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin
      production in a HIF-dependent manner.
AB  - Advanced chronic kidney disease (CKD) patients encounter anemia through
      insufficient erythropoietin (EPO) production by peritubular fibroblasts. Recent
      studies showed an increase in EPO production by pharmacological activation of
      hypoxia-inducible transcription factors (HIFs) in dialysis patients, suggesting
      that desensitization of the oxygen-sensing mechanism is responsible for the
      development of renal anemia. Our recent work demonstrated that indoxyl sulfate
      (IS), a uremic toxin, dysregulates oxygen metabolism in tubular cells. Here we
      provide evidence of an additional property that IS impairs oxygen sensing in EPO
      producing cells. HepG2 cells were stimulated with cobalt chloride (CoCl(2)) or
      hypoxia under varying concentrations of IS. EPO mRNA was evaluated by
      quantitative PCR. Nuclear accumulation of HIF-alpha was evaluated by western
      blotting. Transcriptional activity of HIF was checked by hypoxia-responsive
      element (HRE)-luciferase reporter assay. The impact of IS was further evaluated
      in vivo by administering rats with indole, a metabolic precursor of IS, and
      subjecting them to CoCl(2) stimulation, in which renal EPO mRNA as well as plasma
      EPO levels were measured by quantitative PCR and enzyme-linked immunosorbent
      assay, respectively. Although IS induced cellular toxicity at relatively high
      concentrations (?2.5 mM), EPO mRNA expression was significantly suppressed by IS
      at concentrations below cytotoxic ranges. In HepG2 cells, IS treatment decreased
      nuclear accumulation of HIF-alpha proteins and suppressed HRE-luciferase activity
      following hypoxia. Furthermore, administration of rats with indole suppressed
      renal EPO mRNA expression and plasma EPO levels, corroborating in vitro findings.
      Results of the present study provide a possible connection between a uremic toxin
      and the desensitization of the oxygen-sensing mechanism in EPO-producing cells,
      which may partly explain inadequate EPO production in hypoxic kidneys of CKD
      patients.

PMID- 21863065
TI  - Primary synovial sarcoma of kidney-a report of 2 cases and review of literature.
AB  - BACKGROUND: Primary kidney sarcomas are rare neoplasms. Pre-operative signs and
      symptoms are non-specific, thus making early diagnosis of this condition
      difficult. The presenting features are similar to other common renal tumors.
      MATERIALS AND METHODS: Two cases of primary renal synovial sarcoma were diagnosed
      based on histopathology and immunohistochemistry (IHC). Fusion gene product
      analysis was also done for one patient. RESULTS: Both patients underwent radical
      nephrectomy. The morphology and IHC of the tumors were consistent with primary
      synovial sarcoma of the kidney. One of the patients received adjuvant
      chemotherapy and is on regular follow-up since two years. The second patient was
      lost to follow-up. CONCLUSION: These tumors should be correctly diagnosed because
      the line of treatment is distinct from primary renal cell carcinoma. Chemotherapy
      has a role in managing these patients. KEY WORDS: Synovial sarcoma - kidney - RT
      PCR - SYTSSX - t (X;18) translocation - Fusion gene..

PMID- 21863066
TI  - Preoperative radiotherapy in resectable rectal cancer: a prospective randomized
      study of two different approaches.
AB  - BACKGROUND: Preoperative radiotherapy in resectable rectal cancer has a number of
      potential advantages, most importantly reducing local recurrence, increasing
      survival and down-staging effect. PURPOSE: This prospective study was designed to
      compare between two different approaches of preoperative radiotherapy, either
      short course or long course radiotherapy. The primary endpoint is to evaluate the
      local recurrence rate, overall survival (OS) and disease free survival (DFS). The
      secondary endpoint is to evaluate downstaging, treatment toxicity and ability to
      do sphincter sparing procedure (SSP), aiming at helping in the choice of the
      optimal treatment modality. PATIENTS AND METHODS: This is a prospective
      randomized study of patients with resectable rectal cancer who presented to the
      department of Clinical Oncology and Nuclear Medicine, Mansoura University during
      the time period between June 2007 and September 2009. These patients received
      preoperative radiotherapy and were randomized into two arms: Arm 1, short course
      (SCRT) 25Gy/week/5 fractions followed by surgery within one week, and arm 2, long
      course preoperative radiotherapy (LCRT) 45Gy/5 weeks/25 fractions followed by
      surgery after 4-6 weeks. Adjuvant chemotherapy was given 4-6 weeks after surgery
      according to the postoperative pathology. RESULTS: After a median follow-up of 18
      months (range 6 to 28 months), we studied the patterns of recurrence. Three
      patients experienced local recurrence (LR), two out of 14 (14.2%) in arm 1 & one
      out of 15 patients (6.7%) in arm 2, (p=0.598). Three patients developed distant
      metastases [two in arm 1 (14.2%) & one in arm 2 (6.7%), p=0.598]. Two-year OS
      rate was 64+/-3% & 66+/-2%, (p= 0.389), and the 2-year DFS rate was 61+/-2% &
      83+/-2% for arms 1 & 2, respectively (p=0.83). Tumor (T) downstaging was more
      achieved in LCRT arm with a statistically significant difference, but did not
      reach statistical significance in node (N) down-staging. SSP was more available
      in LCRT but with no statistically significant difference (p=0.082). CONCLUSION:
      This work showed that there was no statistically significant difference between
      SCRT & LCRT as regard local control, distant metastasis, and rate of SSP, OS and
      DFS, while there was a statistically significant difference as regard down
      staging in favor of LCRT. Further follow up is needed to determine late toxicity
      and difference in survival. KEY WORDS: Resectable rectal cancer - Preoperative
      radiotherapy - Short course radiotherapy - Long course radiotherapy.

PMID- 21863064
TI  - Pharmacological mechanisms underlying the antinociceptive and tolerance effects
      of the 6,14-bridged oripavine compound 030418.
AB  - AIM: To investigate possible pharmacological mechanisms underlying the
      antinociceptive effect of and tolerance to N-methyl-7alpha-[(R)-1-hydroxy-1
      methyl-3-(thien-3-yl)-propyl]-6,14-endo-ethanotetrahydronororipavine (030418), a
      derivative of thienorphine. METHODS: The binding affinity and efficacy of 030418
      were determined using receptor binding and guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) assays in CHO-MU, CHO-kappa, CHO
      delta, and CHO-ORL1 cell membranes. The analgesic activity of and tolerance to
      030418 were evaluated in thermal nociceptive tests in mice. The effects of 030418
      on opioid receptors were further investigated using in vivo pharmacological
      antagonist blockade and in vitro tissue preparations. RESULTS: The compound
      030418 displayed high binding affinity to all subtypes of opioid receptors with
      K(i) values in the nanomolar range. In [(35)S]GTPgammaS binding assay, the
      maximal stimulation of 030418 to MU-, kappa-, delta-receptors and the ORL1
      receptor was 89%, 86%, 67% and 91%, respectively. In hot-plate test, the
      antinociceptive effect of 030418 was more potent and longer than morphine. The
      nonselective opioid receptor antagonist naloxone could completely block 030418
      induced antinociception, while both the MU-opioid receptor antagonist beta-FNA
      and the kappa-opioid receptor antagonist nor-BNI attenuated 030418-induced
      antinociception. In contrast, the ORL1 receptor antagonist J-113397 enhanced the
      antinociceptive effect of 030418. Additionally, chronic treatment with 030418
      resulted in a dramatic development of tolerance that could not be effectively
      prevented by J-113397. In guinea pig ileum preparation, the existing action of
      030418 could be removed with difficulty after prolonged washing. CONCLUSION: The
      compound 030418 is a novel agonist of opioid receptors with high efficiency, long
      lasting effect and liability to tolerance, which may be closely correlated with
      the methyl group at the N(17) position and the high hydrophobicity of the C(7)
      thiophene group in its chemical structure.

PMID- 21863067
TI  - Concurrent chemoradiation in locally advanced head and neck cancers: a
      comparative study of weekly Paclitaxel versus Cisplatin-based regimen.
AB  - BACKGROUND: Concurrent chemoradiotherapy is the standard of care for patients
      with unresectable locally advanced squamous cell carcinoma of head and neck
      (LASCCHN). The optimal chemotherapy agents and their dose schedules have yet to
      be defined. Cisplatin improves the anti-tumour efficacy of radiation therapy (RT)
      with 5-year loco-regional control rates between 35-70%. The last decade witnessed
      the introduction of new chemotherapeutic agents. Among these, taxane-based
      chemotherapies emerged as one of the most powerful compounds that might improve
      loco-regional control. The aim of this study was to compare the outcome and
      toxicity of weekly paclitaxel with weekly cisplatin-based concurrent
      chemoradiation in LA-SCCHN. PATIENTS AND METHODS: Fifty two untreated patients
      with LA-SCCHN were enrolled in a chemoradiation feasibility study in the Oncology
      Department, Assuit University Hospital, between the time period from November
      2006 to September 2008 of whom forty one patients were eligible for the study.
      The patients were randomized into 2 groups; group I (21 patients) who received
      paclitaxel 30mg/m2 I.V 1 hour infusion weekly and group II (20 patients) received
      Cisplatin 30mg/m2, I.V 2 hours infusion weekly, both during the course of
      radiation therapy. All patients received 66-70Gy concurrent radiation using a
      linear accelerator with 6mv photons, at the rate of 2Gy/day, 5 fractions/week,
      over a period of 6-7 weeks. Response was assessed according to WHO criteria and
      toxicity according to Radiation Therapy Oncology Group (RTOG) acute radiation
      morbidity scoring criteria and NCI-CTC version 2. RESULTS: Complete response was
      achieved in 57.1% of patients in group I and 50% of patients in group II while
      partial response was achieved in 28.6% in group I and 25% in group II. Thus, the
      objective overall response was 85.7% in group I versus 75% in group II with no
      statistically significant difference (p=0.3). The median duration of follow-up
      was 15 months in group I (range 9- 28 months) while it was 16.5 months for group
      II (range7- 29 months). The median progression free survival (PFS) was 26 months
      for group I and 22 months for group II. The 1-year PFS was 80.7% and 64% for
      group I and group II while the 2-year PFS were 52.2 and 41.1% for group I and
      group II respectively with no statistically significant difference (p=0.5). The
      median survival was 27 and 25 months for group I and II respectively. The1-year
      overall survival (OS) was 80.7% and 64.6% for group I and II while the 2-year OS
      was 58.4 and 46% for group I and group II respectively with no statistically
      significant difference (p=0.41). Treatment toxicities including skin reactions,
      mucositis and dysphagia were comparable in both groups and tolerable. CONCLUSION:
      The results of weekly paclitaxel schedule in the treatment of LA-SCCHN were
      comparable to those of weekly cisplatin schedule with no additional efficacy. So,
      concurrent chemoradiotherapy with weekly paclitaxel is feasible when
      contraindication to cisplatin exists as in cases of fear of hearing loss or renal
      disease. KEY WORDS: Chemoradiation - Paclitaxel - Cisplatin - Locally advanced
      head and neck cancers.

PMID- 21863068
TI  - The Clinical Implications of Methylated p15 and p73 Genes in Adult Acute
      Lymphoblastic Leukemia.
AB  - BACKGROUND: Aberrant methylation of promoterassociated CpG islands is an
      epigenetic modification of DNA which is associated with gene silencing. It plays
      an important role in the leukemia pathogenesis. This phenomenon is frequently
      observed in acute lymphoblastic leukemia (ALL) and results in the functional
      inactivation of its associated genes. The aim of this study is to investigate the
      frequency and the prognostic impact of p15 and p73 genes methylation in adult
      acute lymphoblastic leukemia patients. PATIENTS AND METHODS: Methylation-specific
      polymerase chain reaction (PCR) was used to analyze methylation of the p15 and
      p73 genes in 51 newly diagnosed adult ALL patients. RESULTS: The methylation
      frequencies of p15 and p73 genes at diagnosis were 41.2% and 27.5% respectively,
      while concomitant methylation was detected in 14% of the patients. Concomitant
      methylation of p15 and p73 genes was associated with significant lower rate of CR
      compared to patients without methylation (57% versus 90%), p=0.008. Overall
      survival (OS) was not affected by p15 methylation, but was poorer with p73
      methylation and the difference was near significant (p=0.059). For patients
      without meyhylation, the survival benefit was significant when compared to
      patients with p15, p73 or both genes methylation (p=0.047). The leukemia free
      survival was not affected by the methylation status of single gene p15 or p73,
      but tended to be worse in patients with methylated p15, p73 or both genes when
      compared to patients without methylation (p=0.08). CONCLUSION: Aberrant p73
      promoter methylation is a potential prognostic factor in adult ALL patients. P15
      methylation is frequent in Egyptian adult ALL patients, its concomitant
      methylation with p73 is of poor prognostic significance. Identification of these
      molecular targets improve risk assessment and selection of appropriate therapy.
      KEY WORDS: Methyaltion - p15 - p73 - Adult acute lymphoblastic leukemia.

PMID- 21863069
TI  - Trachelectomy: a review of 15 cases.
AB  - OBJECTIVE: To determine the indications and complications of removal of the
      retained cervical stump (trachelectomy). MATERIALS AND METHODS: Retrospective
      review of the records of 15 cases of removal of the retained cervical stump
      performed at the Department of Surgical Oncology NCI Cairo University and Nasser
      Institute Cairo between January 2005 and December 2009. RESULTS: Fifteen patients
      were identified with a mean age of 43.1+/-8.4 years. The indications for subtotal
      hysterectomy were uterine fibroids, 7 (46.7%), abnormal bleeding, 5 (33.3%), and
      ovarian mass, 3 (20%) cases. Route of trachelectomy was abdominal in all cases.
      The indications for trachelectomy were cervical malignancy in 8 (53.3%), residual
      tumor at the hysterectomy specimen in 3 (20%), and persistent bleeding in 2
      (13.3%) cases. The most common concomitant procedures with the trachelectomy were
      pelvic lymphadenectomy in 11 (73.3%), and oophorectomy in 10 (66.6%) cases. There
      were no postoperative mortalities. The most common complications were wound
      infection, 4 (26.6%), and urinary tract infection, 3 (20%). The mean estimated
      blood loss was 341.0+/- 82.3ml. Hospital stay was 7.9+/-5.1 days. The most common
      histological diagnosis was squamous carcinoma 9 cases (60%). The median follow-up
      period was 16 months. CONCLUSION: Subtotal hysterectomy carries the risk of
      developing a stump cancer. Patient agreement is mandatory. Subtotal hysterectomy
      should be avoided whenever possible in populations with restricted access to
      screening programs for cancer of the uterine cervix. KEY WORDS: Trachelectomy -
      Cervical stump.

PMID- 21863070
TI  - Telomerase expression as complementary prognostic factor in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NB) is an aggressive tumor of childhood with a highly
      heterogeneous course. Identification of standard prognostic factors has several
      limitations. Hence, there is an increasing demand to identify new prognostic
      factors and tools that help in risk stratification of patients for proper
      treatment. OBJECTIVE: To assess the prognostic and predictive impact of
      quantitative telomerase expression in NB patients. METHODS: We investigated
      quantitative telomerase expression by immunohistochemistry in 44 neuroblastoma
      patients. Results were correlated with standard prognostic factors, n-myc
      amplification by chromogen in situ hybridization (CISH) and patients' response to
      treatment and survival. RESULTS: High telomerase expression and n-myc expression
      were reported in 52.3% and 56.8% ; respectively. There was a significant relation
      between telomerase expression and n-myc amplification. Stage 3 and 4 represented
      91% of patients. Thirteen patients showed complete remission, 9 partial
      remission, 19 no response and 3 showed progressive disease. The median followup
      was 3 years with 80% overall and 72% progression free survival for the low
      teleomerase expression group; and 52.2% and 55.4% for high teleomerase expression
      group. High Telomerase expression by immunohistochemistry was significantly
      associated with n-myc amplification and with poor response to treatment with a
      trend toward lower overall and progression free survival. CONCLUSIONS: Telomerase
      expression by immunohistochemistry is a simple potential tool for risk
      stratification of NB patients. CISH can serve as a readily available alternative
      simple tool, compared to FISH, in identifying neuroblastoma cases with abnormal n
      myc gene copy number. KEY WORDS: Telomerase expression- N-myc amplification-
      Prognosis- Neuroblastoma.

PMID- 21863071
TI  - Treatment Outcome of Pediatric Patients with Mature B Cell Lymphoma Receiving Fab
      LMB96 Protocol at the National Cancer Institute, Cairo University.
AB  - INTRODUCTION: Lymphomas are the third most common malignant tumor in the
      pediatric age group after leukemia and brain tumors. Outcome has improved
      remarkably over the past decade because of improvements in imaging and staging
      systems that more accurately reflect the clinical behavior, and the development
      of risk adapted multiagent chemotherapeutic regimens. The aim of this work is to
      study the outcome, Overall Survival (OS) and Event Free Survival (EFS) of
      patients receiving FAB LMB96 protocol applied for treatment of mature B cell
      lymphoma. PATIENTS AND METHODS: This is a retrospective study analyzing the data
      of 103 newly diagnosed pediatric NHL [Burkitt's lymphoma/leukemia, Diffuse Large
      B Cell Lymphoma (DLBCL)] who received LMB96 protocol at Department of Pediatric
      Oncology, National Cancer Institute, Cairo University, during the time period
      from 1st of January 2006 to the end of December 2008. A total of 103 patients
      were included in the study, and were followedup till 31st December 2009. RESULTS:
      This study included were 80 males (77.7%) and 23 females (22.3%), their mean age
      was 6.55+/-3.9 years ranged from 2 to 16 years. Abdominal presentation was the
      most common clinical presentation seen in 85 patients (82.5%) followed by
      thoracic mass in 27 patients (26.2%) and cervical mass in 22 patients (21.4%).
      CNS involvement occurred in 16 patients (15.5%) while bone marrow infiltration
      occurred in 18 patients (17.5%). The most common pathological subtype was
      Burkitt's lymphoma seen in 83 patients (80.6%) followed by DLBCL in 12 patients
      (11.7%). Stage III was the most commonly seen; detected in 65 patients (63.1%).
      The commonest treatment group seen was group B in 80 patients (77.7%) followed by
      group C in 19 patients (18.4%) then group A in 4 patients (3.9%).Complete
      remission for the whole group of patients was achieved in 72 patients (70%),
      relapses and disease progression occurred in 9 patients (8.7%) and stable disease
      in 1 patient (1%). Death due to septicemia occurred in 13 patients (12.6%). There
      were 8 patients (7.7%) who discontinued treatment. CONCLUSION: FAB LMB96 protocol
      is well tolerated, giving results close to the international literature for both
      group A and B patients, while it seems toxic for group C patients. KEY WORDS: NHL
      FAB LMB96- Pediatric- Lymphoma.

PMID- 21863072
TI  - Clinicopathologic significance of molecular classification of breast cancer:
      relation to nottingham prognosis index.
AB  - PURPOSE: The aim of this work is to determine the possible relationship between
      the different profiles of molecular expression of hormone receptors and Her-2/neu
      receptors to clinical and histopathological known prognostic variables for breast
      cancer. MATERIALS AND METHODS: A total of 110 breast carcinoma tumor samples were
      included. In this study 4 groups or immunohistochemical profiles were defined,
      based on expression of hormone receptors (estrogen and/or progesterone) and/or
      Her2/neu (Luminal A, Luminal B, HER2 overexpressing profile, and triple-negative
      profile). We studied whether there were differences between them regarding
      clinical and histopathological variables with a known prognostic significance in
      addition to Nottingham Prognosis Index (NPI). RESULTS: In this series, 65 cases
      corresponded to Luminal A (59.1%), 18 cases (16.4%) were Luminal B, in 14 cases
      (12.7%) HER2 was over-expressed, while 13 cases (11.8%) were of the triple
      negative subtype. It is worth noting the relationship between the triple negative
      and HER2 over-expressing immunophenotypes and the high NPI (>3.4) in comparison
      with the Luminal A and Luminal B immunophenotypes (p=.029). The association of
      the former two types with higher tumor grade was also observed, but such
      association did not reach statistical significance. CONCLUSION: The subgroups
      without hormone receptor expression, with Her2/neu overexpression or without
      (triple-negative group), have characteristics associated with variables of a
      poorer prognosis. KEY WORDS: Breast cancer- Hormone receptors- Her2neu-
      Classification- Nottingham prognosis index.

PMID- 21863073
TI  - Assessment of the reliability of immunocytochemical detection of estrogen and
      progesterone receptors status on the cytological aspirates of breast carcinoma.
AB  - PURPOSE: Evaluation of the reliability of immunocytochemical staining for
      estrogen and progesterone receptor status on previously papanicolaou-stained fine
      needle aspiration smears of breast carcinoma cases. PATIENTS AND METHODS: This is
      a retrospective study conducted on destained smears of fine needle aspirates
      (FNA) obtained from 90 breast carcinoma cases. These cases underwent subsequent
      tumor resection and immunohistochemical detection of estrogen and progesterone
      receptors allowing a comparison between the immunocytochemical and
      immunohistochemical results (Gold Standard). Hypocelluar slides were excluded
      from the current study. Only the nuclear staining was considered specific. The
      results were scored on the basis of the percentage of the positive nuclei among
      the total epithelial malignant cells after examination of the entire slide.
      Smears were interpreted as positive if 10% of the examined cells demonstrated
      nuclear staining. These results were then compared with the immunohistochemical
      results. RESULTS: For estrogen receptor immunocytochemistry, the overall cyto
      histologic accuracy was 91.1% (82/90) while the discordance rate was 8.9% (8/90).
      The diagnostic sensitivity, specificity, positive predictive value, and negative
      predictive value were 93%, 84.2%, 95.7%, and 76.2% respectively. For progesterone
      receptor immunocytochemistry, the overall cyto-histologic accuracy was 88.9%
      (80/90) while the discordance rate was 11.1% (10/90). The diagnostic sensitivity,
      specificity, positive predictive value, and negative predictive value were 87.1%,
      95%, 98.4%, and 67.9% respectively. CONCLUSION: Immunocytochemistry is considered
      as an efficient tool in evaluating estrogen and progesterone receptor status in
      breast carcinoma. The application of estrogen and progesterone receptor
      immunocytochemistry on previously Papanicolaou-stained slides provides an overall
      accuracy of 91.1% for estrogen receptor and 88.9% for progesterone receptor when
      compared with the immunohistochemical results. KEY WORDS: Estrogen receptor-
      Progesterone receptor- Breast carcinoma- FNA- Immunocytochemistry.

PMID- 21863074
TI  - Management of CML in the Pediatric Age Group: Imatinib Mesylate or SCT.
AB  - BACKGROUND: Management of CML has changed markedly since the introduction of
      tyrosine kinase inhibitors (TKIs). However stem cell transplantation (SCT)
      remains a valid therapeutic modality especially in developing countries due to
      its relatively lower cost. We aim to compare between imatinib mesylate and SCT as
      regard outcome in CML in the pediatric age group. METHODS: Forty-eight patients
      with newly diagnosed CML in the chronic phase, aged 3 to 18 years were enrolled
      in this prospective study. Patients without a matched donor (Group I; N=30) were
      assigned to receive imatinib mesylate at a dose of 340mg/m2/day, while patients
      with a fully matched related donor (Group II; N=18), were offered SCT. Response
      (hematologic, cytogenetic and molecular), side effects and survival were
      analyzed. RESULTS: Complete hematologic response was obtained in 97% of the
      patients in group I and 94% in group II. Major cytogenetic response (CyR) was
      obtained in 80% of patients in group I and 100% in group II. Complete CyR was 57%
      in group I and 64% in group II. Major molecular response (MMR) was 36% in group I
      and 50% in group II with no significant difference between both groups. Six years
      overall survival (OS) was 87% in the 1st group and 61% in the 2nd group (p<0.01),
      while eventfree survival (EFS) was 66% in the 1st group and 50% in the 2nd group
      with a highly significant difference between both groups (p<0.01). Side effects
      were generally rare and mild in the imatinib arm, while adverse events were more
      severe and common in the SCT group (55% had GVHD and 78% had infection).
      CONCLUSION: Imatinib mesylate has a superior OS and EFS than SCT in children. It
      is generally safe and well tolerated. Imatinib mesylate should be the 1st line
      treatment of pediatric patients with CML in the chronic phase. KEY WORDS: CML-
      Imatinib- SCT- Pediatrics.

PMID- 21863075
TI  - Using Multidetector CT in Predicting Resectability of Pancreatic Head Tumors:
      Surgical and Pathologic Correlation.
AB  - BACKGROUND: Computed tomography (CT) is widely used to pre-operatively evaluate
      patients with pancreatic tumors. AIM: The purpose of this study is to evaluate
      retrospectively, the ability of multi-detector computed tomography (MDCT) to
      predict resectability of pancreatic cancer on the basis of surgical outcome and
      pathologic correlation. PATIENTS AND METHODS: Sixty nine consecutive patients
      presenting between January 2007 and June 2010 with pancreatic head tumors were
      included in the study. The study group comprised patients with pancreatic head
      tumors from the local catchment area and others referred to our tertiary care
      center from surrounding hospitals. Sixty nine examinations were performed with
      the same 64 slice CT scan (Brillinat Philips). All patients were imaged using a
      standardized MDCT protocol. Patients with disease that was clearly inoperable
      were excluded from the study. The remaining patients (32) had their CT studies
      double-reported using a standard method. Images were scored for vascular
      involvement, tumor size and the presence of distant metastases. Surgical and
      pathologic reports were reviewed and compared to CT results. Frequencies, mean
      and range were used as descriptive statistics, positive predictive value (PPV)
      and negative predictive value (NPV) and sensitivity, specificity and accuracy
      were done using SPSS version 18 program. RESULTS: Of the 32 patients evaluated,
      65.6% had successful resection of pancreatic head tumors; while 34.4% had a
      palliative procedure. When compared to surgical outcome, the positive predictive
      value of multidetector computed tomography for resectability was 100%. On the
      basis of pathologic results (considering the surgical technique and the positive
      surgical margin as a microscopic picture), the negative predictive value of multi
      detector computed tomography for resectability fell to 65.5%, Three patients
      deemed resectable following multi-detector computed tomography had positive
      margins at pathology. CONCLUSION: There is improved prediction of resectability /
      unresectability with the introduction of MDCT. When compared to Helical computed
      tomography (HCT) studies, there is a rise in the rate of successful surgical
      resection with a concomitant decrease in the rate of palliative surgery. The
      positive predictive value of multidetector computed tomography for resectable
      disease is lower when pathologic correlation, as opposed to surgical correlation,
      is used as the gold standard. KEY WORDS: Multidetector computed tomography (MDCT)
      Resectability/unresectability prediction- Pancreatic head tumors.

PMID- 21863076
TI  - In vivo animal histomorphometric study for evaluating biocompatibility and
      osteointegration of nano-hydroxyapatite as biomaterials in tissue engineering.
AB  - The coming decade will bring new and even more complex advances that will
      transform oral and maxillofacial surgery practice if the specialty is capable of
      transferring the advances of basic science into clinical practice. Such advances
      include those in tissue engineering and nanotechnology. Three groups of eight
      animals (rats), each was evaluated by grouting bone graft substitutes into 3 mm
      holes that were made into the anteromedialtibialmetaphyses of rats. Two different
      formulations varying as to the type of hydroxyapatite (HA) were used; Group 1:
      Nano-hydroxyapatite, Group 2: Control with HA only. Group 3: Control without any
      bone graft substitutes (empty defects). Animals of each of the three groups were
      sacrificed in groups of eight at postoperative week four. Histologic analysis
      revealed superior biocompatibility and osteointegration of bone graft substitutes
      when nanohydroxyapatite was employed. At four weeks, there was more reactive new
      bone formation in this group when compared to the hydroxyapatite group. The
      control group showed incomplete closure of the defect. This study demonstrated
      that nano-hydroxyapatite improves the bioactivity of bone implant and repair
      materials. Nanohydroxyapatite has good biocompatibility, finer mechanical
      properties, adjustable degradation properties, good osteointegration and offers a
      wide range of potential applications in the tissue engineering. KEY WORDS:
      Osteointegration- Nano-Hydroxyapatite- Biomaterials- Tissue engineering.

PMID- 21863077
TI  - Pre-prosthetic surgical alterations in maxillectomy to enhance the prosthetic
      prognoses as part of rehabilitation of oral cancer patient.
AB  - After maxillectomy, prosthetic restoration of the resulting defect is an
      essential step because it signals the beginning of patient's rehabilitation. An
      obturator used to restore the defect should be comfortable, restore adequate
      speech, deglutition, and mastication, and is acceptable cosmetically, Success
      will depend on the size and location of the defect and the quantity and integrity
      of the remaining structures, in addition to pre-prosthetic surgical preparation
      of the defect sit. Preoperative cooperation between the surgeon oncologists and
      the maxillofacial surgeon may allow obturation of a resultant defect by
      preservation of the premaxilla or the tuberosity on the defect side and
      maintaining the alveolar bone adjacent to the defect of an abutment tooth. This
      study was carried out to evaluate the importance of Pre-prosthetic surgical
      alterations at the time of maxillectomy on the enhancement of the prosthetic
      prognoses as part of rehabilitation of the oral cancer patient. The present study
      was carried out on 66 cancer patient, 41 males 25 females ages ranging from 33 to
      72 years, seeking treatment between 2003-2008 at The National Cancer Institute,
      Cairo university they underwent immediate prosthetic rehabilitation after
      maxillectomy surgery to remove the malignant tumor as apart of cancer treatment.
      Patients were divided into groups according to preprosthetic surgical preparation
      before prosthetic restoration. GROUP(A): Resection of maxilla followed by
      preprosthatic surgical preparation 24 cancer patients (13 males- 11 femals).
      GROUP(B): Resection of maxilla without any preprosthetic surgical preparation. 42
      cancer patients (28 males and 14 females). Outcome variables measured included
      facial contour and aesthetic results, speech understandability, ability to eat
      solid foods, oronasal separation, socializing outside the home, and return-to
      work status. Flap success and donor site morbidity were also studied. This study
      concluded that the cornerstone to improve the prosthetic restoration of the
      maxillary defect resulting maxillary resection as part of the treatment of
      maxillofacial tumor depend on the close cooperation between the prosthodontist
      and the surgeon, this can be achieved by combination of surgical and prosthetic
      technique which can be controlled by pre-prosthetic surgery during maxillect omy.
      KEY WORDS: Maxillary re-construction- Pre-prosthetic surgery- Oral cancer.

PMID- 21863078
TI  - Phenacetin and analgesic mixtures containing phenacetin.

PMID- 21863079
TI  - Phenazopyridine hydrochloride.

PMID- 21863080
TI  - Phenolphthalein.

PMID- 21863081
TI  - Phenoxybenzamine hydrochloride.

PMID- 21863082
TI  - Phenytoin and phenytoin sodium.

PMID- 21863083
TI  - Polybrominated biphenyls.

PMID- 21863084
TI  - Polychlorinated biphenyls.

PMID- 21863086
TI  - Procarbazine and its hydrochloride.

PMID- 21863085
TI  - Polycyclic aromatic hydrocarbons: 15 Listings - benz[a]anthracene,
      benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene,
      dibenz[a,h]acridine, dibenz[a,j]acridine, dibenz[a,h]anthracene, 7H
      dibenzo[c,g]carbazole, dibenzo[a,e]pyrene, dibenzo[a,h]pyrene,
      dibenzo[a,i]pyrene, dibenzo[a,l]pyrene, indeno[1,2,3-cd]pyrene, 5-methylchrysene.

PMID- 21863087
TI  - Progesterone.

PMID- 21863088
TI  - 1,3-Propane sultone.

PMID- 21863089
TI  - beta-Propiolactone.

PMID- 21863090
TI  - Propylene oxide.

PMID- 21863091
TI  - Propylthiouracil.

PMID- 21863092
TI  - Reserpine.

PMID- 21863093
TI  - Safrole.

PMID- 21863094
TI  - Selenium sulfide.

PMID- 21863095
TI  - Silica, crystalline (respirable size).

PMID- 21863096
TI  - Soots.

PMID- 21863097
TI  - Strong inorganic acid mists containing sulfuric acid.

PMID- 21863098
TI  - Styrene-7,8-oxide.

PMID- 21863099
TI  - Sulfallate.

PMID- 21863100
TI  - Tamoxifen.

PMID- 21863101
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

PMID- 21863102
TI  - Tetrachloroethylene.

PMID- 21863103
TI  - Tetrafluoroethylene.

PMID- 21863104
TI  - Tetranitromethane.

PMID- 21863105
TI  - Thioacetamide.

PMID- 21863106
TI  - Thiotepa.

PMID- 21863107
TI  - Thiourea.

PMID- 21863108
TI  - Tobacco-related exposures: tobacco smoking.

PMID- 21863109
TI  - Tobacco-related exposures: environmental tobacco smoke.

PMID- 21863110
TI  - Tobacco-related exposures: smokeless tobacco.

PMID- 21863111
TI  - Toluene diisocyanates.

PMID- 21863112
TI  - o-Toluidine and its hydrochloride.

PMID- 21863113
TI  - Toxaphene.

PMID- 21863114
TI  - Trichloroethylene.

PMID- 21863115
TI  - 2,4,6-Trichlorophenol.

PMID- 21863116
TI  - Tris(2,3-dibromopropyl) phosphate.

PMID- 21863117
TI  - Ultraviolet radiation related exposures: solar radiation, exposure to sunlamps or
      sunbeds, broad-spectrum UVR, UVA, UVB, UVC.

PMID- 21863118
TI  - Urethane.

PMID- 21863119
TI  - 4-Vinyl-1-cyclohexene diepoxide.

PMID- 21863120
TI  - Vinyl halides (selected): vinyl bromide.

PMID- 21863121
TI  - Vinyl halides (selected): vinyl chloride.

PMID- 21863122
TI  - Vinyl halides (selected): vinyl fluoride.

PMID- 21863123
TI  - Wood dust.

PMID- 21863124
TI  - 4,4'-Thiodianiline.

PMID- 21863125
TI  - Complete set of material properties of single domain 0.24Pb(In(1/2)Nb(1/2))O(3)
      0.49Pb(Mg(1/3)Nb(2/3))O(3)-0.27PbTiO(3) single crystal and the orientation
      effects.
AB  - Multidomain relaxor-based single crystals have intrigued the enthusiasm of many
      researchers due to their superior electromechanical properties. In order to
      understand the physical origin of multidomain properties, one must know the
      complete set of material coefficients in single domain state. Previous published
      single domain data were all measured under bias because single domain state is
      unstable. Here, we report a set of single domain data without bias for
      rhombohedral 0.24Pb(In(1/2)Nb(1/2))O(3)-0.49Pb(Mg(1/3)Nb(2/3))O(3)-0.27PbTiO(3)
      single crystal. Comparing rotated coefficients from single domain data with
      measured multidomain material coefficients, we concluded that the orientation
      effects account for more than 90% of the observed multidomain properties.

PMID- 21863126
TI  - Sequential shrink photolithography for plastic microlens arrays.
AB  - Endeavoring to push the boundaries of microfabrication with shrinkable polymers,
      we have developed a sequential shrink photolithography process. We demonstrate
      the utility of this approach by rapidly fabricating plastic microlens arrays.
      First, we create a mask out of the children's toy Shrinky Dinks by simply
      printing dots using a standard desktop printer. Upon retraction of this pre
      stressed thermoplastic sheet, the dots shrink to a fraction of their original
      size, which we then lithographically transfer onto photoresist-coated commodity
      shrink wrap film. This shrink film reduces in area by 95% when briefly heated,
      creating smooth convex photoresist bumps down to 30 um. Taken together, this
      sequential shrink process provides a complete process to create microlenses, with
      an almost 99% reduction in area from the original pattern size. Finally, with a
      lithography molding step, we emboss these bumps into optical grade plastics such
      as cyclic olefin copolymer for functional microlens arrays.

PMID- 21863127
TI  - Phylogenomics-based reconstruction of protozoan species tree.
AB  - We have developed a semi-automatic methodology to reconstruct the phylogenetic
      species tree in Protozoa, integrating different phylogenetic algorithms and
      programs, and demonstrating the utility of a supermatrix approach to construct
      phylogenomics-based trees using 31 universal orthologs (UO). The species tree
      obtained was formed by three major clades that were related to three groups of
      data: i) Species containing at least 80% of UO (25/31) in the concatenated
      multiple alignment or supermatrix, this clade was called C1, ii) Species
      containing between 50%-79% (15-24/31) of UO called C2, and iii) Species
      containing less than 50% (1-14/31) of UO called C3. C1 was composed by only
      protozoan species, C2 was composed by species related to Protozoa, and C3 was
      composed by some species of C1 (Protozoa) and C2 (related to Protozoa). Our
      phylogenomics-based methodology using a supermatrix approach proved to be
      reliable with protozoan genome data and using at least 25 UO, suggesting that (a)
      the more UO used the better, (b) using the entire UO sequence or just a conserved
      block of it for the supermatrix produced similar phylogenomic trees.

PMID- 21863128
TI  - On differential gene expression using RNA-Seq data.
AB  - MOTIVATION: RNA-Seq is a novel technology that provides read counts of RNA
      fragments in each gene, including the mapped positions of each read within each
      gene. Besides many other applications it can be used to detect differentially
      expressed genes. Most published methods collapse the position-level read data
      into a single gene-specific expression measurement. Statistical inference
      proceeds by modeling these gene-level expression measurements. RESULTS: We
      present a Bayesian method of calling differential expression (BM-DE) that
      directly models the position-level read counts. We demonstrate the potential
      advantage of the BM-DE method compared to existing approaches that rely on gene
      level aggregate data. An important additional feature of the proposed approach is
      that BM-DE can be used to analyze RNA-Seq data from experiments without
      biological replicates. This becomes possible since the approach works with
      multiple position-level read counts for each gene. We demonstrate the importance
      of modeling for position-level read counts with a yeast data set and a simulation
      study. AVAILABILITY: A public domain R package is available from
      http://odin.mdacc.tmc.edu/~ylji/BMDE/.

PMID- 21863129
TI  - Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of
      Analgesics.
AB  - Low molecular weight opioid peptide esters (OPE) could become a class of
      analgesics with different side effect profiles than current opiates. OPE may have
      sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester
      hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly
      conjugated to ethanol have a structure similar to the anesthestic agent,
      etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski's
      criteria, and permeability of select GABA esters to cross the BBB, opioid
      peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead
      recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester
      crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no
      approved OP analgesics available for clinical use. Clinical trials of good
      manufacturing practice OP administered to patients suffering from chronic pain
      with indwelling intrathecal pumps could resolve the issue that OP may be superior
      to opiates and may redirect research.

PMID- 21863130
TI  - Altered Endoplasmic Reticulum Calcium Pump Expression during Breast
      Tumorigenesis.
AB  - Endoplasmic reticulum calcium homeostasis is involved in several essential cell
      functions including cell proliferation, protein synthesis, stress responses or
      secretion. Calcium uptake into the endoplasmic reticulum is performed by
      Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). In order to study
      endoplasmic reticulum calcium homeostasis in situ in mammary tissue, in this work
      SERCA3 expression was investigated in normal breast and in its benign and
      malignant lesions in function of the cell type, degree of malignancy, and
      histological and molecular parameters of the tumors. Our data indicate, that
      although normal breast acinar epithelial cells express SERCA3 abundantly, its
      expression is strongly decreased already in very early non-malignant epithelial
      lesions such as adenosis, and remains low in lobular carcinomas. Whereas normal
      duct epithelium expresses significant amounts of SERCA3, its expression is
      decreased in several benign ductal lesions, as well as in ductal adenocarcinoma.
      The loss of SERCA3 expression is correlated with Elston-Ellis grade, negative
      hormone receptor expression or triple negative status in ductal carcinomas. The
      concordance between decreased SERCA3 expression and several histological, as well
      as molecular markers of ductal carcinogenesis indicates that endoplasmic
      reticulum calcium homeostasis is remodeled during tumorigenesis in the breast
      epithelium.

PMID- 21863133
TI  - Climbing for preventing and treating health problems: a systematic review of
      randomized controlled trials.
AB  - OBJECTIVE: To summarize the best available evidence on effectiveness of
      therapeutic or sport climbing in preventing or treating health problems. METHODS:
      We searched Medline, Embase, CENTRAL, PsycINFO, PEDro, OTseeker and SportDiscus
      for randomized controlled trials published up to December 26, 2010. We included
      all trials assessing patient-relevant outcomes. Two reviewers independently
      selected relevant studies, assessed their methodological quality and extracted
      data. Quality of evidence was rated using the GRADE system. Data were entered
      into RevMan 5 to calculate effect sizes and 95% confidence intervals where
      appropriate. RESULTS: Eligible for inclusion were four RCTs studying the
      effectiveness of climbing in (a) geriatric patients, (b) adults with multiple
      sclerosis, (c) adults with chronic low-back pain and (d) children with
      disabilities and poor motor function. The sample sizes ranged between 20 and 95.
      All trials had major methodological limitations. We found very low quality
      evidence that therapeutic climbing may improve activities of daily living in
      geriatric patients compared to physiotherapy as measured by the Barthel index
      (difference in mean change score: 2.32 [95%-CI: 0.45 to 4.19]). We found very low
      quality evidence that therapeutic climbing compared to standard exercise therapy
      may improve physical functioning (difference in mean change score: 16.15 [95%-CI:
      4.45 to 27.85]) and general physical health (13.14 [95%-CI: 3.61 to 22.67]) as
      measured by the SF-36 in adults with chronic low back-pain. CONCLUSIONS: Evidence
      for the effectiveness of therapeutic climbing is limited to small trials at high
      risk of bias. The effects of therapeutic climbing are therefore unclear.

PMID- 21863132
TI  - Pulsing with blast cell lysate or blast-derived total RNA reverses the dendritic
      cell-mediated cytotoxic activity of cytokine-induced killer cells against
      allogeneic acute myelogenous leukemia cells.
AB  - Immunotherapeutic strategies may be a treatment option in patients with
      refractory acute myelogenous leukemia (AML) or, in cases of complete remission
      after conventional therapy regimens, may help to reduce disease recurrence or
      delay time to progression. Evidence suggests a key role of dendritic cells (DCs)
      in cancer immunotherapy due to their capacity to present tumour antigens to
      effector cells. We generated cytokine-induced killer (CIK) cells from healthy
      donors and examined their responses in vitro in an LDH release assay against
      three cell lines and allogeneic HLA non-matched blasts from three patients with
      de novo AML after coincubation with autologous peripheral blood monocyte-derived
      DCs. Although DCs were unable to enhance CIK cell effects against all three cell
      lines tested, the cytotoxic activity against the patients' AML cells increased
      after coculture with mature DCs, which was significant in two of three patients.
      However, neither prior pulsing of the DCs with blast cell lysates nor with
      leukemic cell-derived total RNA further enhanced the lytic capacity of the CIK
      cells. On the contrary, pulsing reduced or even reversed the cytotoxic activity
      of the effector cells. This decrease of allogeneic cytotoxicity led us to
      conclude that monocyte-derived DCs may be useful in autologous or allogeneic
      vaccine strategies for the treatment of AML or in priming donor lymphocytes in
      vitro, but unfractionated antigens as pulsing agents may have inhibitory effects
      on T cell efficiency and their employment in immunotherapeutic strategies for AML
      seems questionable.

PMID- 21863131
TI  - Management options in triple-negative breast cancer.
AB  - Notorious for its poor prognosis and aggressive nature, triple-negative breast
      cancer (TNBC) is a heterogeneous disease entity. The nature of its biological
      specificity, which is similar to basal-like cancers, tumors arising in BRCA1
      mutation carriers, and claudin-low cancers, is currently being explored in hopes
      of finding the targets for novel biologics and chemotherapeutic agents. In this
      review, we aim to give a broad overview of the disease's nomenclature and
      epidemiology, as well as the basic mechanisms of emerging targeted therapies and
      their performance in clinical trials to date.

PMID- 21863134
TI  - Effects of CPAP-respiration on markers of glucose metabolism in patients with
      obstructive sleep apnoea syndrome: a systematic review and meta-analysis.
AB  - BACKGROUND: Obstructive Sleep Apnoea Syndrome (OSAS) is a condition of
      obstruction, apneas and arousals while sleeping. It has been suggested that OSAS
      independently influences glucose metabolism. The main treatment for OSAS is
      continuous positive airways pressure (CPAP). OBJECTIVES: To assess the effects of
      CPAP on insulin resistance and glucose metabolism. SEARCH STRATEGY: We searched
      Medline, Embase and the Cochrane Controlled Trial Register (January 2010).
      SELECTION CRITERIA: We included randomised and non-randomised trials comparing
      CPAP with inactive control or placebo CPAP in adults with OSAS. DATA COLLECTION
      AND ANALYSIS: Two authors independently assessed trial quality and extracted
      data. Parallel and crossover group trials were analysed separately. A meta
      analysis was carried out. RESULTS: Three parallel group and two cross-over
      randomised trials and one controlled trial were included investigating 296
      participants. Sample sizes ranged from n=13 to n=102 participants, age was 18 to
      75 years, mean body mass index (BMI) 27.2 kg/m2 to 37.1 kg/m2, mean apnoe
      hypopnoe index (AHI) 29.7 to 39.7 events per hour, mean dips >4% in arterial
      oxygen saturation per hour of sleep 1 to 42.7 events. The studies' methodological
      quality varied. Follow-up ranged from 4 to 12 weeks. Various endpoints were
      investigated. CPAP did neither influence plasma insulin levels nor HOMA-index,
      adiponectin levels or HbA1c value. One study reported a significant positive
      effect on the insulin sensitivity index (1.68%/min, 95% CI 0.3 to 3.06).
      CONCLUSION: This systematic review does not support the hypothesis that OSAS
      independently influences glucose metabolism. Sufficiently powered, long-term
      randomised controlled trials defining changes of insulin resistance as primary
      endpoint are needed.

PMID- 21863135
TI  - Results of a quality control on non-interventional studies.
AB  - Non-interventional studies (NIS) have for decades been an established part of
      post-authorisation medicinal research. As early as the mid-nineties, there were
      at least rudimentary demands for controllable data quality. Beginning with the
      recommendations of the Federal Institute for Drugs and Medical Devices (BfArM) on
      the execution of non interventional (observational) studies of 1998 and finally
      with the guidelines and recommendations for ensuring Good Epidemiological
      Practice (GEP), with the VFA (Verband der forschenden Arzneimittelhersteller
      [German Association of Research-Based Pharmaceutical Companies]) -
      Recommendations for the Improvement of Quality and Transparency of NIS and the
      joint recommendations of BfArM and PEI (Paul-Ehrlich-Institut) on the execution
      of NIS, pharmaceutical companies are required to monitor and/or verify quality in
      the course of a project. According to a survey of pharmaceutical companies 2010,
      about one third of the companies surveyed to date carry out such quality controls
      on site, at participating study centres. This report deals with the results of
      such quality control measures in 4 completed projects. The control rates defined
      in the respective cohort study plans, the measures carried out on site and any
      consequent measures, such as adjustment of forms, reduction of consultation time
      and necessary organisational changes are described. A high level of agreement
      between the data collected and the original patient documents is found,
      comparable to that in clinical trials.

PMID- 21863136
TI  - Effect of aging on esophageal motility in patients with and without GERD.
AB  - BACKGROUND/AIMS: The impact of aging on esophageal motility is not completely
      understood. This study aims at assessing 1) whether degeneration of esophageal
      body motility occurs with age and 2) whether this development is influenced by
      gastroesophageal reflux disease (GERD). METHODS: 326 consecutive patients with
      symptoms of GERD underwent a diagnostic work-up including a water-perfused
      esophageal manometry. Patients were divided by age: 17-39 years (group 1, n=75),
      40-49 years (group 2, n=79), 50-59 years (group 3, n=64), 60-69 years (group 4,
      n=74), and >70 years (group 5, n=34). GERD was diagnosed if patients had erosive
      esophagitis at endoscopy, a positive pH-metry, or both. The amplitude of
      esophageal contraction waves 3 cm and 8 cm above the lower esophageal sphincter
      and the percentage of peristaltic contraction waves of the tubular esophagus were
      analyzed and correlated to GERD. RESULTS: A normal esophageal manometry was found
      in 86.7%, 73.4%, 67.2%, 58.1%, and 55.9% (p<0.01) in groups 1-5, respectively.
      Esophageal contraction wave amplitudes were affected by age in patients positive
      for GERD only (p<0.01). Esophageal body peristalsis was affected by age (p<0.01)
      independent of the diagnosis of GERD. CONCLUSION: Aging is correlated to
      esophageal motor abnormalities. GERD has a significant impact on esophageal
      contraction wave amplitude, but not on peristalsis.

PMID- 21863138
TI  - Imaging of thalamocortical dysrhythmia in neuropsychiatry.
AB  - Abnormal brain activity dynamics, in the sense of a thalamocortical dysrhythmia
      (TCD), has been proposed as the underlying mechanism for a subset of disorders
      that bridge the traditional delineations of neurology and neuropsychiatry. In
      order to test this proposal from a psychiatric perspective, a study using
      magnetoencephalography (MEG) was implemented in subjects with schizophrenic
      spectrum disorder (n = 14), obsessive-compulsive disorder (n = 10), or depressive
      disorder (n = 5) and in control individuals (n = 18). Detailed CNS
      electrophysiological analysis of these patients, using MEG, revealed the presence
      of abnormal theta range spectral power with typical TCD characteristics, in all
      cases. The use of independent component analysis and minimum-norm-based methods
      localized such TCD to ventromedial prefrontal and temporal cortices. The observed
      mode of oscillation was spectrally equivalent but spatially distinct from that of
      TCD observed in other related disorders, including Parkinson's disease, central
      tinnitus, neuropathic pain, and autism. The present results indicate that the
      functional basis for much of these pathologies may relate most fundamentally to
      the category of calcium channelopathies and serve as a model for the cellular
      substrate for low-frequency oscillations present in these psychiatric disorders,
      providing a basis for therapeutic strategies.

PMID- 21863137
TI  - The Role of Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Cognition.
AB  - Striatal-enriched protein tyrosine phosphatase (STEP) has recently been
      implicated in several neuropsychiatric disorders with significant cognitive
      impairments, including Alzheimer's disease, schizophrenia, and fragile X
      syndrome. A model has emerged by which STEP normally opposes the development of
      synaptic strengthening and that disruption in STEP activity leads to aberrant
      synaptic function. We review the mechanisms by which STEP contributes to the
      etiology of these and other neuropsychiatric disorders. These findings suggest
      that disruptions in STEP activity may be a common mechanism for cognitive
      impairments in diverse illnesses.

PMID- 21863139
TI  - Large-Scale Analysis of Gene Expression and Connectivity in the Rodent Brain:
      Insights through Data Integration.
AB  - Recent research in C. elegans and the rodent has identified correlations between
      gene expression and connectivity. Here we extend this type of approach to examine
      complex patterns of gene expression in the rodent brain in the context of
      regional brain connectivity and differences in cellular populations. Using
      multiple large-scale data sets obtained from public sources, we identified two
      novel patterns of mouse brain gene expression showing a strong degree of anti
      correlation, and relate this to multiple data modalities including macroscale
      connectivity. We found that these signatures are associated with differences in
      expression of neuronal and oligodendrocyte markers, suggesting they reflect
      regional differences in cellular populations. We also find that the expression
      level of these genes is correlated with connectivity degree, with regions
      expressing the neuron-enriched pattern having more incoming and outgoing
      connections with other regions. Our results exemplify what is possible when
      increasingly detailed large-scale cell- and gene-level data sets are integrated
      with connectivity data.

PMID- 21863140
TI  - Drug Delivery: Enabling Technology for Drug Discovery and Development. iPRECIO
      Micro Infusion Pump: Programmable, Refillable, and Implantable.
AB  - Successful drug delivery using implantable pumps may be found in over 12,500
      published articles. Their versatility in delivering continuous infusion,
      intermittent or complex infusion protocols acutely or chronically has made them
      ubiquitous in drug discovery and basic research. The recent availability of
      iPRECIO((r)), a programmable, refillable, and implantable infusion pump has made
      it possible to carry out quantitative pharmacology (PKPD) in single animals. When
      combined with specialized catheters, specific administration sites have been
      selected. When combined with radiotelemetry, the physiologic gold standard, more
      sensitive and powerful means of detecting drug induced therapeutic, and/or
      adverse effects has been possible. Numerous application examples are cited from
      iPRECIO((r)) use in Japan, United States, and Europe with iPRECIO((r)) as an
      enabling drug delivery device where the refillable and programmability
      functionality were key benefits. The ability to start/stop drug delivery and to
      have control periods prior dosing made it possible to have equivalent effects at
      a much lower dose than previously studied. Five different iPRECIO((r))
      applications are described in detail with references to the original work where
      the implantable, refillable, and programmable benefits are demonstrated with
      their different end-points.

PMID- 21863141
TI  - Post-marketing health technology monitoring. The analysis of an experience from a
      clinical perspective.
AB  - INTRODUCTION: A system for monitoring the use of aphaeresis in the treatment of
      ulcerative colitis (UC), named system for monitoring aphaeresis in ulcerative
      colitis (SiMAC), was designed in 2006 in the Basque Country. In the present
      study, the opinion of the clinicians who participated in SiMAC was evaluated, in
      order to identify the barriers and gather suggestions that could improve
      implementation of this kind of system. METHODS: A mixed questionnaire was
      designed, in order to gather clinicians' assessments of the SiMAC monitoring
      system. RESULTS: The response rate was 73.9% (17/23). The data from 40.96%
      (159/388) of patients with UC treated with aphaeresis was recorded. The main
      reasons for not including the data from all treated patients were a lack of
      required data or not meeting the study inclusion criteria. Positive aspects of
      the SiMAC were identified, as the simplicity of data collection and its
      systematic, multi-center approach. The negative aspects mentioned were the use of
      a local computer application and the lack of time for health professionals to
      enter data. DISCUSSION: The use of monitoring systems helps to formalize the
      introduction of technologies of little-known effectiveness; involve clinicians
      and medical societies in coming to agreement and obtaining information about the
      safety, effectiveness or efficiency of new technologies; and provide relevant
      information to healthcare administrations for making decisions about the
      introduction of new technologies into healthcare practice. In order for a
      monitoring system to work, the process must be straightforward. A minimum set of
      key variables that are easy to collect must be selected, and an effort made to
      involve a range of stakeholders, especially institutions and scientific
      societies, to support the work group.

PMID- 21863142
TI  - Comparisons of Two Proteomic Analyses of Non-Mucoid and Mucoid Pseudomonas
      aeruginosa Clinical Isolates from a Cystic Fibrosis Patient.
AB  - Pseudomonas aeruginosa chronically infects the lungs of cystic fibrosis (CF)
      patients. The conditions in the CF lung appear to select for P. aeruginosa with
      advantageous phenotypes for chronic infection. However, the mechanisms that allow
      the establishment of this chronic infection have not been fully characterized. We
      have previously reported the transcriptional analysis of two CF isolates strains
      383 and 2192. Strain 2192 is a mucoid, alginate overproducing strain whereas
      strain 383 is non-mucoid. Mucoid strains are associated with chronic infection of
      the CF lung and non-mucoid strains are the typical initially infecting isolates.
      To elucidate novel differences between these two strains, we employed two methods
      of shotgun proteomics: isobaric tags for relative and absolute quantitation
      (iTRAQ) and two-dimensional gel electrophoresis (2-DE). iTRAQ compares the amount
      of protein between samples and relies on protein abundance, while 2-DE gel
      electrophoresis depends on selection of separated protein spots. For both these
      methods, mass spectrometry was then used to identify proteins differentially
      expressed between the two strains. The compilation of these two proteomic methods
      along with Western blot analysis revealed proteins of the HSI-I operon of the
      type 6 secretion system, showed increased expression in 383 compared to 2192,
      confirming the our previous transcriptional analysis. Proteomic analysis of other
      proteins did not fully correlate with the transcriptome but other differentially
      expressed proteins are discussed. Also, differences were noted between the
      results obtained for the two proteomic techniques. These shotgun proteomic
      analyses identified proteins that had been predicted only through gene
      identification; we now refer to these as "proteins of unknown functions" since
      their existence has now been established however their functional
      characterization remains to be elucidated.

PMID- 21863143
TI  - New concepts in the evaluation of biodegradation/persistence of chemical
      substances using a microbial inoculum.
AB  - The European REACH Regulation (Registration, Evaluation, Authorization of
      CHemical substances) implies, among other things, the evaluation of the
      biodegradability of chemical substances produced by industry. A large set of test
      methods is available including detailed information on the appropriate conditions
      for testing. However, the inoculum used for these tests constitutes a "black
      box." If biodegradation is achievable from the growth of a small group of
      specific microbial species with the substance as the only carbon source, the
      result of the test depends largely on the cell density of this group at "time
      zero." If these species are relatively rare in an inoculum that is normally used,
      the likelihood of inoculating a test with sufficient specific cells becomes a
      matter of probability. Normally this probability increases with total cell
      density and with the diversity of species in the inoculum. Furthermore the
      history of the inoculum, e.g., a possible pre-exposure to the test substance or
      similar substances will have a significant influence on the probability. A high
      probability can be expected for substances that are widely used and regularly
      released into the environment, whereas a low probability can be expected for new
      xenobiotic substances that have not yet been released into the environment. Be
      that as it may, once the inoculum sample contains sufficient specific degraders,
      the performance of the biodegradation will follow a typical S shaped growth curve
      which depends on the specific growth rate under laboratory conditions, the so
      called F/M ratio (ratio between food and biomass) and the more or less toxic
      recalcitrant, but possible, metabolites. Normally regulators require the
      evaluation of the growth curve using a simple approach such as half-time.
      Unfortunately probability and biodegradation half-time are very often confused.
      As the half-time values reflect laboratory conditions which are quite different
      from environmental conditions (after a substance is released), these values
      should not be used to quantify and predict environmental behavior. The
      probability value could be of much greater benefit for predictions under
      realistic conditions. The main issue in the evaluation of probability is that the
      result is not based on a single inoculum from an environmental sample, but on a
      variety of samples. These samples can be representative of regional or local
      areas, climate regions, water types, and history, e.g., pristine or polluted. The
      above concept has provided us with a new approach, namely "Probabio." With this
      approach, persistence is not only regarded as a simple intrinsic property of a
      substance, but also as the capability of various environmental samples to degrade
      a substance under realistic exposure conditions and F/M ratio.

PMID- 21863145
TI  - Fabrication of Murine Ventricular Balloons for the Langendorff Heart Preparation.
AB  - A method for fabrication of ventricular pressure balloons is presented. Murine
      ventricular balloons with adequately small size, durability and elastic
      characteristics were produced using silicone dispersion. The forms, onto which
      the silicone are coated, are constructed of water soluble materials allowing the
      release of cured silicone balloons with soaking in H(2)O.

PMID- 21863144
TI  - Brain SPECT Imaging in Complex Psychiatric Cases: An Evidence-Based,
      Underutilized Tool.
AB  - Over the past 20 years brain Single Photon Emission Computed Tomography (SPECT)
      imaging has developed a substantial, evidence-based foundation and is now
      recommended by professional societies for numerous indications relevant to
      psychiatric practice. Unfortunately, SPECT in clinical practice is utilized by
      only a handful of clinicians. This article presents a rationale for a more
      widespread use of SPECT in clinical practice for complex cases, and includes
      seven clinical applications where it may help optimize patient care.

PMID- 21863146
TI  - Pregnancy and Protection: The Ethics of Limiting a Pregnant Woman's Participation
      in Clinical Trials.
AB  - The call for the inclusion of pregnant women in clinical trials has received
      renewed attention recently. This interest springs from articles in various
      medical journals highlighting the gaps in medical knowledge and the need to
      improve health care for pregnant women.It is not a simple decision whether to
      include pregnant women in studies or not. The general thought is that it's too
      dangerous for the baby if a pregnant woman is participating in a trial, and the
      absence of research on how medications work in pregnant women leave doctors
      guessing about how to safely and effectively treat patients through
      pregnancy.Excluding pregnant women from clinical trials are not automatic, not
      unethical nor is it arbitrarily determined. The regulatory framework is based on
      sound ethical and legal reasoning that demonstrates when inclusion in a clinical
      trial is appropriate or when clear and compelling reasons for exclusion are
      presented. LEARNING OBJECTIVE: Readers will learn about limitations of research,
      history of the inclusion and exclusion of pregnant women in clinical trials,
      reticence for inclusions, as well as regulations designed using reasoned legal
      and ethical principles, such as: Principle of Autonomy, Informed Consent, and
      Beneficence and Nonmaleficence.

PMID- 21863147
TI  - Observation of bi-polarons in blends of conjugated copolymers and fullerene
      derivatives.
AB  - From a fundamental and application point of view it is of importance to
      understand how charge carrier generation and transport in a conjugated polymer
      (CP):fullerene blend are affected by the blend morphology. In this work light
      induced electron spin resonance (LESR) spectra and transient ESR response signals
      are recorded on non-annealed and annealed blend layers consisting of alkyl
      substituted thieno[3,2-b]thiophene copolymers (pATBT) and the soluble fullerene
      derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) at temperatures
      ranging from 10 to 180 K. Annealing of the blend sample leads to a reduction of
      the steady state concentration of light-induced PCBM anions within the blend at
      low temperatures (T = 10 K) and continuous illumination. This is explained on the
      basis of the reducing interfacial area of the blend composite on annealing, and
      the high activation energy for electron diffusion in PCBM blends leading to
      trapped electrons near the interface with the CP. As a consequence, these trapped
      electrons block consecutive electron transfer from an exciton on a CP to the PCBM
      domain, resulting in a relatively low concentration charge carriers in the
      annealed blend. Analysis of the transient ESR data allows us to conclude that in
      annealed samples diamagnetic bi-polaronic states on the CPs are generated at low
      temperature. The formation of these states is related to the generation and
      interaction of multiple positive polarons in the large crystalline polymer
      domains present in the annealed sample.

PMID- 21863148
TI  - Localized flexible integration of high-efficiency surface enhanced Raman
      scattering (SERS) monitors into microfluidic channels.
AB  - We report here a facile approach for flexible integration of high efficiency
      surface enhanced Raman scattering (SERS) monitors in a continuous microfluidic
      channel. In our work, femtosecond laser direct writing was adopted for highly
      localizable and controllable fabrication of the SERS monitor through a multi
      photon absorption (MPA) induced photoreduction of silver salt solution. The
      silver substrate could be shaped into designed patterns, and could be precisely
      located at the desired position of the microchannel bed, giving the feasibility
      for real-time detection during reactions. SEM and TEM images show that the silver
      substrates were composed of crystallized silver nanoplates with an average
      thickness of 50 nm. AFM results reveal that the substrates were about 600 nm in
      height and the surface was very rough. As representative tests for SERS
      detection, p-aminothiophenol (p-ATP) and flavin adenine dinucleotide (FAD) were
      chosen as probing molecules for microfluidic analysis at visible light (514.5 nm)
      excitation, exhibiting an enhancement factor of ~10(8). In addition, the
      combination of the SERS substrate with the microfluidic channel allows detection
      of inactive analytes through in situ microfluidic reactions.

PMID- 21863149
TI  - A micropump controlled by EWOD: wetting line energy and velocity effects.
AB  - A Laplace pressure gradient between a droplet and a liquid meniscus was utilized
      to create an on-demand constant flow rate capillary pump. Electrowetting on
      dielectric was implemented to induce the pressure gradient in the microchannel.
      For an initial droplet volume of 0.3 MUL and a power of 12 nW a constant flow
      rate of 0.02 MUL s(-1) was demonstrated. The effects of the wetting line energy
      on the static contact angle and the wetting line velocity on the dynamic contact
      angle in the pump operation were studied. Sample loading on-demand could be
      achieved by regulating an electric potential.

PMID- 21863150
TI  - Characteristics of CO3(2-)-water hydrogen bonds in aqueous solution: insights
      from HF/MM and B3LYP/MM MD simulations.
AB  - Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics
      simulations, namely HF/MM and B3LYP/MM, have been performed to investigate the
      local hydration structure and dynamics of carbonate (CO(3)(2-)) in dilute aqueous
      solution. With respect to the QM/MM scheme, the QM region, which contains the
      CO(3)(2-) and its surrounding water molecules, was treated at HF and B3LYP levels
      of accuracy, respectively, using the DZV+ basis set, while the rest of the system
      is described by classical MM potentials. For both the HF/MM and B3LYP/MM
      simulations, it is observed that the hydrogen bonds between CO(3)(2-) oxygens and
      their nearest-neighbor waters are relatively strong, i.e., compared to water
      water hydrogen bonds in the bulk, and that the first shell of each CO(3)(2-)
      oxygen atom somewhat overlaps with the others, which allows migration of water
      molecules among the coordinating sites to exist. In addition, it is observed that
      first-shell waters are either "loosely" or "tightly" bound to the respective
      CO(3)(2-) oxygen atoms, leading to large fluctuations in the number of first
      shell waters, ranging from 1 to 6 (HF/MM) and 2 to 7 (B3LYP/MM), with the
      prevalent value of 3. Upon comparing the HF and B3LYP methods in describing this
      hydrated ion, the latter is found to overestimate the hydrogen-bond strength in
      the CO(3)(2-)-water complexes, resulting in a slightly more compact hydration
      structure at each of the CO(3)(2-) oxygens.

PMID- 21863151
TI  - Fluorescent pyrene-centered starburst oligocarbazoles with excellent thermal and
      electrochemical stabilities.
AB  - A series of pyrene-centered starburst oligocarbazoles (1-3) have been synthesized
      and well characterized. Based on photophysical, thermal and electrochemical
      studies in solutions and as thin films, all starburst molecules reveal a sky blue
      emission with a high efficiency (Phi(F) = 0.99-0.81) and excellent thermal and
      electrochemical stabilities. As OLED materials, these superior properties are
      helpful to enhance device stability and lifetime.

PMID- 21863152
TI  - Palladium-catalyzed C-H acetoxylation of 2-methoxyimino-2-aryl-acetates and
      acetamides.
AB  - Palladium-catalyzed C-H acetoxylation reactions of 2-methoxyimino-2-aryl-acetates
      and acetamides have been developed. These transformations feature excellent
      regioselectivity, wide substrate scope, and moderate to good yields. The product
      can be easily converted into naturally unprecedented alpha-amino acids in
      excellent yields.

PMID- 21863153
TI  - Paper on a disc: balancing the capillary-driven flow with a centrifugal force.
AB  - This paper describes the active control of the capillary-driven flow in paper
      using a centrifugal device.

PMID- 21863154
TI  - One pot synthesis of amino acid derived chiral disubstituted morpholines and 1,4
      oxazepanes via tandem aziridine/epoxide ring opening sequences.
AB  - A new one-pot synthetic strategy is described for the synthesis of
      enantiomerically pure cis-3,5-disubstituted morpholines and 3,6-disubstituted 1,4
      oxazepanes via tandem aziridine/epoxide ring opening sequences. This new strategy
      describes how epoxy alcohols could act as both a nucleophile and an electrophile
      in a tandem fashion and undergo intermolecular regioselective ring opening of
      chiral aziridines for the first time.

PMID- 21863155
TI  - Combinatorial synthesis of galactosyl-1,3,5-triazines as novel nucleoside
      analogues.
AB  - Herein we report a parallel solid-phase synthesis of 1,3,5-triazine based
      nucleoside analogues by a three-step substitution, starting from 2,4,6-trichloro
      1,3,5-triazine. A library of 80 galactosyl-1,3,5-triazine compounds was prepared
      in high purity without extensive reaction conditions or tedious purification,
      suggesting the generality of this method.

PMID- 21863156
TI  - Rational design of a cyclin A fluorescent peptide sensor.
AB  - We report the design and development of a fluorescent sensor specifically
      designed to target cyclin A, a protein that plays a key role in the regulation of
      the cell cycle. Computational studies provide a molecular picture that explains
      the observed emission increase, suggesting that the 4-DMAP fluorophore in the
      peptide is protected from the bulk solvent when inserted into the hydrophobic
      binding groove of cyclin A.

PMID- 21863157
TI  - One-pot three-enzyme synthesis of UDP-GlcNAc derivatives.
AB  - A Pasteurella multocida N-acetylglucosamine 1-phosphate uridylyltransferase
      (PmGlmU) was cloned and used efficiently with an N-acetylhexosamine 1-kinase
      (NahK_ATCC55813) and an inorganic pyrophosphatase (PmPpA) for one-pot three
      enzyme synthesis of UDP-GlcNAc derivatives with or without further chemical
      diversification.

PMID- 21863158
TI  - Aromaticity of strongly bent benzene rings: persistence of a diatropic ring
      current and its shielding cone in [5]paracyclophane.
AB  - Direct evaluation of the induced pi current density in [5]paracyclophane (1)
      shows that, despite the significant non-planarity (alpha = 23.2 degrees )
      enforced by the pentamethylene bridge, there is only a modest (ca. 17%) reduction
      in the pi ring current, justifying the use of shielding-cone arguments for the
      assignment of (1)H NMR chemical shifts of 1 and the claim that the non-planar
      benzene ring in 1 retains its aromaticity (on the magnetic criterion).

PMID- 21863168
TI  - Design and evaluation of synthetic silica-based monolithic materials in
      shrinkable tube for efficient protein extraction.
AB  - Sample pretreatment is a required step in proteomics in order to remove
      interferences and preconcentrate the samples. Much research in recent years has
      focused on porous monolithic materials since they are highly permeable to liquid
      flow and show high mass transport compared with more common packed beds. These
      features are due to the micro-structure within the monolithic silica column which
      contains both macropores that reduce the back pressure, and mesopores that give
      good interaction with analytes. The aim of this work was to fabricate a
      continuous porous silica monolithic rod inside a heat shrinkable tube and to
      compare this with the same material whose surface has been modified with a C(18)
      phase, in order to use them for preconcentration/extraction of proteins. The
      performance of the silica-based monolithic rod was evaluated using eight
      proteins; insulin, cytochrome C, lysozyme, myoglobin, beta-lactoglobulin,
      ovalbumin, hemoglobin, and bovine serum albumin at a concentration of 60 MUM. The
      results show that recovery of the proteins was achieved by both columns with
      variable yields; however, the C(18) modified silica monolith gave higher
      recoveries (92.7 to 109.7%) than the non-modified silica monolith (25.5 to
      97.9%). Both silica monoliths can be used with very low back pressure indicating
      a promising approach for future fabrication of the silica monolith inside a
      microfluidic device for the extraction of proteins from biological media.

PMID- 21863169
TI  - Silver(I) ions and cysteine detection based on photoinduced electron transfer
      mediated by cytosine-Ag(+)-cytosine base pairs.
AB  - Upon formation of cytosine-Ag(+)-cytosine base pairs as a mediator for the
      photoinduced electron transfer, the fluorescence of FAM-labeled DNA was quenched
      and the fluorescence emission wavelength exhibited a red shift. Based on these
      phenomena a novel dual-output fluorescent DNA sensor for Ag(+) ions and cysteine
      detection was developed.

PMID- 21863170
TI  - An electrochemical DNA sensor based on a layers-film construction modified
      electrode.
AB  - This work developed a relatively inexpensive and layers-film construction
      electrochemical sensor for DNA recognition and its performance was investigated.
      The Fe(3)O(4) magnetic nanoparticles-cysteine were immobilized on the carbon
      paste electrode (CPE) surface using magnetic force. Multiwalled carbon nanotubes
      (MWCNTs), gold nanoparticles (GNPs), and chitosan (Chi) were used successively to
      coat on the electrode surface. The thiolated capture probe was assembled and
      competitively hybridized with the target nucleic acid and biotinylated response
      probe. The electrochemical behavior was analyzed by cyclic voltammetry and
      electrochemical impedance spectroscopy. In addition, the sensor performance was
      also analyzed by introducing the notion of detection efficiency. The experimental
      results showed that although the electron transfer capability of the CPE is less
      strong than that of a metal electrode used in the DNA sensor, the materials
      modified on the CPE could significantly improve the performance. A detection
      limit of 1 nM of target DNA and a sensitivity of 2.707 * 10(3) mA M(-1) cm(-2)
      were obtained. Although the resulting detection limit was not remarkable, further
      experiments could improve it.

PMID- 21863171
TI  - Yolk/shell nanoparticles: new platforms for nanoreactors, drug delivery and
      lithium-ion batteries.
AB  - Yolk/shell or 'rattle-typed' nanomaterials with nanoparticle cores inside hollow
      shells are interesting among the complex hollow nanostructures. Yolk/shell
      nanoparticles (YSNs) are promising functional nanomaterials for a variety of
      applications such as catalysis, delivery, lithium-ion batteries and biosensors
      due to their tailorability and functionality in both the cores and hollow shells.
      This feature article provides an overview of advances in this exciting area of
      YSNs, covering systematic synthesis approaches and key promising applications
      based on the literature and our own recent work. We present some strategies for
      the synthesis of YSNs with controllable sizes, compositions, geometries,
      structures and functionalities. Applications of these new materials in a wide
      range of potential areas are discussed including nanoreactors, biomedicine and
      lithium-ion batteries. Promising future directions of this active research field
      are also highlighted.

PMID- 21863172
TI  - Synthesis of architecturally well-defined nanogels via RAFT polymerization for
      potential bioapplications.
AB  - Nanogel synthesis by RAFT polymerization is an emerging field for the control of
      architectures and functions of polymeric nanomaterials for bioapplications. In
      this Feature Article, we review the recent development in nanogel synthesis using
      preformed RAFT polymers and by direct RAFT polymerizations.

PMID- 21863173
TI  - A novel magnetic mesoporous silica packed S-shaped microfluidic reactor for
      online proteolysis of low-MW proteome.
AB  - Magnetic mesoporous silica with a magnetic cover and mesoporous core was
      synthesized, filled with trypsin and located in an S-shaped microfluidic reactor.
      High-molecular weight (MW) proteins were split to waste by fractionation, whilst
      low-MW proteins were retained on the chip to be digested.

PMID- 21863174
TI  - [60]Fullerene-based monolayers as neuroprotective biocompatible hybrid materials.
AB  - Here we report on the surface immobilization of redox-active [60]fullerene
      derivatives and the consequent neuroprotective effects toward l-glutamate induced
      excitotoxicity in human derived undifferentiated neuroblastoma cells.

PMID- 21863175
TI  - Synthesis of the ABH rings of ecteinascidin 597 using a connective Pummerer-type
      cyclisation.
AB  - A connective Pummerer-type cyclisation involving a cysteine derivative and an N
      benzyl glyoxamide 3 has been applied in an asymmetric synthesis of the protected
      ABH rings 2 of the antitumour and antimicrobial natural product ecteinascidin
      597.

PMID- 21863176
TI  - Intrastrand locks increase duplex stability and base pairing selectivity.
AB  - Oligodeoxynucleotide probes with disulfide locks between neighboring nucleobases
      show increases in melting point for duplexes with RNA target strands of up to 7.6
      degrees C. The weakly pairing TT dimers are replaced with locked 2'-deoxy-5
      (thioalkynyl)uridine residues via automated synthesis.

PMID- 21863177
TI  - Formation of ultracold SrYb molecules in an optical lattice by photoassociation
      spectroscopy: theoretical prospects.
AB  - State-of-the-art ab initio techniques have been applied to compute the potential
      energy curves for the SrYb molecule in the Born-Oppenheimer approximation for the
      electronic ground state and the first fifteen excited singlet and triplet states.
      All the excited state potential energy curves were computed using the equation of
      motion approach within the coupled-cluster singles and doubles framework and
      large basis-sets, while the ground state potential was computed using the coupled
      cluster method with single, double, and noniterative triple excitations. The
      leading long-range coefficients describing the dispersion interactions at large
      interatomic distances are also reported. The electric transition dipole moments
      have been obtained as the first residue of the polarization propagator computed
      with the linear response coupled-cluster method restricted to single and double
      excitations. Spin-orbit coupling matrix elements have been evaluated using the
      multireference configuration interaction method restricted to single and double
      excitations with a large active space. The electronic structure data were
      employed to investigate the possibility of forming deeply bound ultracold SrYb
      molecules in an optical lattice in a photoassociation experiment using continuous
      wave lasers. Photoassociation near the intercombination line transition of atomic
      strontium into the vibrational levels of the strongly spin-orbit mixed
      b(3)Sigma(+), a(3)Pi, A(1)Pi, and C(1)Pi states with subsequent efficient
      stabilization into the v'' = 1 vibrational level of the electronic ground state
      is proposed. Ground state SrYb molecules can be accumulated by making use of
      collisional decay from v'' = 1 to v'' = 0. Alternatively, photoassociation and
      stabilization to v'' = 0 can proceed via stimulated Raman adiabatic passage
      provided that the trapping frequency of the optical lattice is large enough and
      phase coherence between the pulses can be maintained over at least tens of
      microseconds.

PMID- 21863178
TI  - Effects of the surface mobility on the oxidation of adsorbed CO on platinum
      electrodes in alkaline media. The role of the adlayer and surface defects.
AB  - The oxidation of adsorbed CO on Pt single crystal electrodes has been studied in
      alkaline media. The surfaces used in this study were the Pt(111) electrode and
      vicinal stepped and kinked surfaces with (111) terraces. The kinked surfaces have
      either (110) steps broken by (100) kinks or (100) steps broken by (110) kinks and
      different kink densities. The voltammetric profiles for the CO stripping on those
      electrodes show peaks corresponding to the oxidation of CO on the (111) terraces,
      on the (100) steps/kinks and on the (110) steps/kinks at very distinctive
      potentials. Additionally, the stripping voltammograms always present a prewave.
      The analysis of the results with the different stepped and kinked surfaces
      indicates that the presence of the prewave is not associated with defects or
      kinks in the electrode surface. Also, the clear separation of the CO stripping
      process in different peak contributions indicates that the mobility of CO on the
      surface is very low. Using partial CO stripping experiments and studies at
      different pH, it has been proposed that the low mobility is a consequence of the
      negative absolute potential at which the adlayers are formed in alkaline media.
      Also, the surface diffusion coefficient for CO in these media has been estimated
      from the dependence of the stripping charge of the peaks with the scan rate of
      the voltammetry.

PMID- 21863179
TI  - Synthesis and characterization of axial heterojunction inorganic-organic
      semiconductor nanowire arrays.
AB  - The end-to-end P-N heterojunction nanowire arrays combined organic (poly[1,4
      bis(pyrrol-2-yl)benzene], BPB) and inorganic (CdS) molecules have been
      successfully designed and fabricated. The electrical properties of P-N
      heterojunctions of organic-inorganic nanowire arrays were investigated. The diode
      nature and rectifying feature of P-N heterojunction nanowire arrays were
      observed. The rectification ratio of the diode increased from 29.9 to 129.7 as
      the illumination intensity increased. The material exhibits a new property, which
      is an improvement in the integration of the physical and chemical properties of
      the two independent components.

PMID- 21863180
TI  - Mercury wet deposition in rural Korea: concentrations and fluxes.
AB  - The characteristics of Hg wet deposition were investigated in a rural area of
      Korea from August 2006 to July 2008. The volume weighted mean (VWM) Hg(T)
      concentration and cumulative Hg(T) flux were 8.8 ng L(-1) and 9.4 MUg m(-2) per
      year, respectively. The VWM Hg(T) concentration varied seasonally, similar to the
      seasonal pattern in atmospheric Hg(p) concentration. The enhancement of both VWM
      Hg(T) and atmospheric Hg(p) concentrations in spring and winter was likely caused
      by the long-range transport of Hg from China. Monthly VWM Hg(T) and atmospheric
      Hg(p) concentrations were well correlated (R(2) = 0.36); however, there was no
      correlation between VWM Hg(T) and RGM (reactive gaseous mercury) concentrations,
      suggesting that Hg(p) was responsible for the majority of the Hg in wet
      deposition at this site. The VWM Hg(T) concentration in snow was statistically
      higher than in rain. In addition, the atmospheric Hg(p) concentration appeared to
      be elevated for snow events as well. This suggests that both elevated Hg(p)
      concentrations and the enhanced scavenging efficiency of snow for Hg(p) were
      responsible for the elevated VWM Hg(T) concentrations measured during snow
      events.

PMID- 21863181
TI  - Microtopographical assembly of cardiomyocytes.
AB  - One of the central challenges in cardiac tissue engineering is the control of the
      assembly and organization of functional cardiac tissue. Maintenance of a three
      dimensional tissue architecture is key to myocardial function in vivo, and a
      variety of studies hint that provision of topological cues within scaffolds can
      facilitate the engineering of functional myocardial tissue by promoting this
      architecture. To explore this possibility in an isolated and well-defined
      fashion, we have designed scaffolds of polydimethylsiloxane (PDMS) with
      microtopographic pillars ("micropegs") to provide cells with defined structures
      with which to interact in three dimensions. We show that these surfaces permit HL
      1 cardiomyocytes to grow, form myofibrillar structures and cell-cell adhesions,
      and beat spontaneously. Additionally, the cells and their nuclei interact with
      the full length of the micropegs, indicating that the micropegs promote a three
      dimensional cytoarchitecture in the context of a two-dimensional scaffold. We
      also show that the number of cells interacting with a micropeg can be controlled
      by manipulating incubation time, micropeg spatial arrangement, or micropeg
      diameter. Western blots reveal that the expression of the junctional markers N
      cadherin and connexin 43 is upregulated in the presence of specific arrangements
      of micropegs, suggesting that micropegs can enhance cardiomyocyte function.
      Together, these data show that microtopography can be used to provide three
      dimensional adhesion and control the assembly of functional cardiac tissue on a
      two-dimensional surface.

PMID- 21863182
TI  - Microchip-based immunomagnetic detection of circulating tumor cells.
AB  - Screening for circulating tumor cells (CTCs) in blood has been an object of
      interest for evidence of progressive disease, status of disease activity,
      recognition of clonal evolution of molecular changes and for possible early
      diagnosis of cancer. We describe a new method of microchip-based immunomagnetic
      CTC detection, in which the benefits of both immunomagnetic assay and the
      microfluidic device are combined. As the blood sample flows through the
      microchannel closely above arrayed magnets, cancer cells labeled with magnetic
      nanoparticles are separated from blood flow and deposited at the bottom wall of
      the glass coverslip, which allows direct observation of captured cells with a
      fluorescence microscope. A polydimethylsiloxane (PDMS)-based microchannel fixed
      on a glass coverslip was used to screen blood samples. The thin, flat dimensions
      of the microchannel, combined with the sharp magnetic field gradient in the
      vicinity of arrayed magnets with alternate polarities, lead to an effective
      capture of labeled cells. Compared to the commercially available CellSearchTM
      system, fewer (25%) magnetic particles are required to achieve a comparable
      capture rate, while the screening speed (at an optimal blood flow rate of 10 mL
      h(-1)) is more than five times faster than those reported previously with a
      microchannel-based assay. For the screening experiment, blood drawn from healthy
      subjects into CellSaveTM tubes was spiked with cultured cancer cell lines of
      COLO205 and SKBR3. The blood was then kept at room temperature for 48 hours
      before the screening, emulating the actual clinical cases of blood screening.
      Customized Fe(3)O(4) magnetic nanoparticles (Veridex FerrofluidTM) conjugated to
      anti-epithelial cell adhesion molecule (EpCAM) antibodies were introduced into
      the blood samples to label cancer cells, and the blood was then run through the
      microchip device to capture the labelled cells. After capture, the cells were
      stained with fluorescent labelled anti-cytokeratin, DAPI and anti-CD45.
      Subsequent immunofluorescence images were taken for the captured cells, followed
      by comprehensive computer aided analysis based on fluorescence intensities and
      cell morphology. Rare cancer cells (from ~1000 cells down to ~5 cells per mL)
      with very low tumor cell to blood cell ratios (about 1 : 10(7) to 10(9),
      including red blood cells) were successfully detected. Cancer cell capture rates
      of 90% and 86% were demonstrated for COLO205 and SKBR3 cells, respectively.

PMID- 21863183
TI  - A microfluidic device that generates hydroxyl radicals to probe the solvent
      accessible surface of nucleic acids.
AB  - We describe a microfluidic device containing a mineral matrix capable of rapidly
      generating hydroxyl radicals that enables high-resolution structural studies of
      nucleic acids. Hydroxyl radicals cleave the solvent accessible backbone of DNA
      and RNA; the cleavage products can be detected with as fine as single nucleotide
      resolution. Protection from hydroxyl radical cleavage (footprinting) can identify
      sites of protein binding or the presence of tertiary structure. Here we report
      preparation of micron sized particles of iron sulfide (pyrite) and fabrication of
      a microfluidic prototype that together generate enough hydroxyl radicals within
      20 ms to cleave DNA sufficiently for a footprinting analysis to be conducted.
      This prototype enables the development of high-throughput and/or rapid reaction
      devices with which to probe nucleic acid folding dynamics and ligand binding.

PMID- 21863184
TI  - Chiral phosphoproline-catalyzed asymmetric Michael addition of ketones to
      nitroolefins: an experimental and theoretical study.
AB  - A novel pyrrolidine-based chiral phosphoproline is an effective bifunctional
      organocatalyst for the asymmetric Michael addition of ketones to nitroolefins
      giving high levels of diastereo- and enantio-selectivities (up to > 99 : 1 dr and
      96% ee). anti-SR Transition state has the lowest barrier which controls the
      stereoselectivity, in agreement with experimental results.

PMID- 21863185
TI  - New imidazopyridopyrimidine:naphthyridine base-pairing motif, ImN(N):NaO(O),
      consisting of a DAAD:ADDA hydrogen bonding pattern, markedly stabilize DNA
      duplexes.
AB  - The new imidazopyridopyrimidine:naphthyridine base-pairing motifs, ImO(O):NaN(N)
      and ImN(N):NaO(O), were designed. Among the base pairs examined, DNA duplexes
      containing ImN(N):NaO(O) pair(s) consisting of a DAAD:ADDA hydrogen bonding
      pattern (D = donor, A = acceptor) were markedly stabilized thermally and
      thermodynamically.

PMID- 21863186
TI  - Direct electrochemistry of an [FeFe]-hydrogenase on a TiO2 electrode.
AB  - [FeFe]-hydrogenases are efficient natural catalysts that can be exploited for
      hydrogen production. Immobilization of the recombinant [FeFe]-hydrogenase CaHydA
      was achieved for the first time on an anatase TiO(2) electrode. The enzyme is
      able to interact and exchange electrons with the electrode and to catalyze
      hydrogen production with an efficiency of 70%.

PMID- 21863187
TI  - Efficient coating of polystyrene microspheres with graphene nanosheets.
AB  - Herein, we propose a facile and efficient method to obtain the
      polystyrene/graphene nanosheets (PS/GNSs) nanocomposite particles. As far as we
      know, it is the first example that GNSs are attached onto the surface of PS
      microspheres, with such smooth morphology, and without relying on any surface
      pretreatments of substrate microspheres.

PMID- 21863188
TI  - X-ray absorption, photoemission spectroscopy, and Raman scattering analysis of
      amorphous tantalum oxide with a large extent of oxygen nonstoichiometry.
AB  - The electronic structure and modification of the local interatomic structure of a
      reactive sputtered amorphous tantalum oxide (a-TaO(x)) thin film with the
      variation of oxygen nonstoichiometry, x in a-TaO(x) have been investigated by X
      ray absorption spectroscopy (XAS), X-ray photoemission spectroscopy (XPS), Raman
      scattering spectroscopy, and Rutherford back scattering spectroscopy. A parallel
      chemical shift of Ta4f(7/2) and O1s core levels observed with the variation of x
      indicates the Fermi level shift by reduction and oxidation in the framework of
      the rigid band model. Extended X-ray absorption fine structure (EXAFS) suggests
      both the increase of average coordination number of the first Ta-O shell in
      polyhedra and a considerable reduction of the average Ta-O bond length with the
      increase of x. The relative intensity of Raman shift peaks at 670 cm(-1) and 815
      cm(-1), corresponding to Ta-O stretching of TaO(6) octahedra and TaO(5) probably
      with a pyramidal form, respectively, drastically changes between x = 2.47 to
      1.86, suggesting the change in the predominant polyhedron from TaO(6) to TaO(5)
      with a modification in multiplicity of oxygen by the reorganization of the
      polyhedral network.

PMID- 21863189
TI  - Quantitative tracking of the growth of individual algal cells in microdroplet
      compartments.
AB  - In this paper we introduce a simple droplet-based microfluidic system consisting
      of two separate devices to encapsulate and culture microalgae, in contrast to
      cultivation in bulk liquid medium. This microdroplet technology has been used to
      monitor the growth of individual microalgal cells in a constant environment for
      extended periods of time. Single cells from three species of green microalgae,
      (two freshwater species Chlamydomonas reinhardtii and Chlorella vulgaris, and one
      saline species Dunaliella tertiolecta), were encapsulated and incubated in
      microdroplet compartments of diameter of ~80 MUm, and their growth analysed over
      10 days. In all cases, the doubling time of microalgae grown in microdroplets was
      similar to growth in bulk. The growth of C. reinhardtii in microdroplets of
      varying diameters and with different initial cell numbers per droplet was
      investigated, as well as the effect of varying medium conditions such as pH and
      nitrogen concentration. This methodology offers the opportunity to study
      characteristics over time of individual cells and colonies, as well as to screen
      large numbers of them.

PMID- 21863190
TI  - Magnetically separable Prussian blue analogue Mn3[Co(CN)6]2.nH2O porous nanocubes
      as excellent absorbents for heavy metal ions.
AB  - The application of Prussian blue analogue (PBA) Mn(3)[Co(CN)(6)](2).nH(2)O porous
      nanocubes as absorbents for heavy metal ions has been demonstrated. The result
      indicates that Mn(3)[Co(CN)(6)](2).nH(2)O porous nanocubes with average diameter
      of 240 nm possess excellent adsorption efficiency for Pb(2+) ions (94.21% at
      initial Pb(2+) concentration of 10 mg L(-1)). Moreover,
      Mn(3)[Co(CN)(6)](2).nH(2)O porous nanocubes can also show high adsorption
      efficiency on heavy metal ions even in a strong acidic solution due to its
      chemical stability. Notably, an external magnet could be used to accelerate the
      separation of Mn(3)[Co(CN)(6)](2).nH(2)O from the treated solution. It is
      suggested that the high adsorption efficiency may derive from the large surface
      area, M(3)(II)[M(III)(CN)(6)](2).nH(2)O porous framework structure and affinity
      between polarizable pi-electron clouds of the cyanide bridges and heavy metals
      ions.

PMID- 21863191
TI  - Aurophilic interactions as a subject of current research: an up-date.
AB  - Recently accumulated experimental evidence for aurophilic interactions in and
      between molecular gold(I) compounds and the results of pertinent theoretical
      calculations are reviewed for the period from 2007 to mid-2011. The influence of
      the intra- and intermolecular bonding contacts between the closed-shell metal
      centres, Au-Au, on the molecular and crystal structures, and the consequences of
      these effects for the chemical and physical properties of gold compounds are
      summarized for the various classes of mono- and polynuclear systems. The
      literature survey builds on the contents of previous reviews and relates new
      experimental and theoretical findings to earlier observations (353 references).

PMID- 21863192
TI  - Dynamic behaviour of Ru and Ru-Pt complexes containing tetrahedro-P4 ligand.
AB  - Dynamic processes involving the P(4) cage coordinated to transition metal
      fragments were observed for the mononuclear complex trans-[Ru(dppm)(2)(H)(eta(1)
      P(4))]BF(4) and for the bimetallic derivative trans-[Ru(dppm)(2)(H)(MU ,eta(1:2)
      P(4)){Pt(PPh(3))(2)}]BF(4) as demonstrated by NMR experiments and DFT
      calculations.

PMID- 21863193
TI  - Synthesis of novel beta-aminocyclobutanecarboxylic acid derivatives by a solvent
      free aza-Michael addition and subsequent ring closure.
AB  - Novel beta-aminocyclobutanecarboxylic acid derivatives were prepared via a
      sequential solvent-free aza-Michael addition of benzophenone imine across 3
      halopropylidenemalonates and base-induced ring closure. These highly substituted
      cyclobutanedicarboxylic acid derivatives were subjected to a reactivity study
      which demonstrated the tendency of these donor-acceptor substituted four-membered
      rings to be converted into their corresponding ring-opened products.

PMID- 21863194
TI  - A synthetic approach to kingianin A based on biosynthetic speculation.
AB  - A synthetic approach towards the structurally complex dimer, kingianin A is
      reported. The strategy involved a cascade of complexity generating reactions,
      inspired through biosynthetic speculation. A concise protecting group free
      synthesis of the proposed monomeric precursor pre-kingianin A has been achieved
      using a tandem Stille cross-coupling reaction and electrocyclisation process.
      However, preliminary studies of the key dimerisation reaction have been
      conducted, which indicate that the process is not spontaneous, raising questions
      as to the origin of this complex natural product.

PMID- 21863195
TI  - The preparation of 2H-1,4-benzoxazin-3-(4H)-ones via palladium-catalyzed
      intramolecular C-O bond formation.
AB  - Pd/PtBu(3)-catalyzed intramolecular C-O bond formation has been used to access
      aryl- and alkyl-substituted benzoxazinones.

PMID- 21863196
TI  - Synthesis of tert-butyl peresters from aldehydes by Bu4NI-catalyzed metal-free
      oxidation and its combination with the Kharasch-Sosnovsky reaction.
AB  - A new tert-butyl peresters synthesis directly from aldehydes and TBHP was
      developed via Bu(4)NI-catalyzed aldehyde C-H oxidation. Mechanistic studies
      suggest that the protocol proceeds via a radical process. Combining the method
      with the Kharasch-Sosnovsky reaction offers a practical approach for the
      synthesis of allylic esters from simple aldehydes and alkenes via a two-step one
      pot procedure.

PMID- 21863197
TI  - Catalytic conversion of lignocellulosic biomass to fine chemicals and fuels.
AB  - Lignocellulosic biomass is the most abundant and bio-renewable resource with
      great potential for sustainable production of chemicals and fuels. This critical
      review provides insights into the state-of the-art accomplishments in the
      chemocatalytic technologies to generate fuels and value-added chemicals from
      lignocellulosic biomass, with an emphasis on its major component, cellulose.
      Catalytic hydrolysis, solvolysis, liquefaction, pyrolysis, gasification,
      hydrogenolysis and hydrogenation are the major processes presently studied.
      Regarding catalytic hydrolysis, the acid catalysts cover inorganic or organic
      acids and various solid acids such as sulfonated carbon, zeolites,
      heteropolyacids and oxides. Liquefaction and fast pyrolysis of cellulose are
      primarily conducted over catalysts with proper acidity/basicity. Gasification is
      typically conducted over supported noble metal catalysts. Reaction conditions,
      solvents and catalysts are the prime factors that affect the yield and
      composition of the target products. Most of processes yield a complex mixture,
      leading to problematic upgrading and separation. An emerging technique is to
      integrate hydrolysis, liquefaction or pyrolysis with hydrogenation over
      multifunctional solid catalysts to convert lignocellulosic biomass to value-added
      fine chemicals and bio-hydrocarbon fuels. And the promising catalysts might be
      supported transition metal catalysts and zeolite-related materials. There still
      exist technological barriers that need to be overcome (229 references).

PMID- 21863198
TI  - Aromatic residues link binding and function of intrinsically disordered proteins.
AB  - We have searched for intermolecular aromatic pairs in 77 protein-protein
      complexes of intrinsically disordered proteins (IDPs) to understand the role of
      pi-pi interactions in protein-protein interactions involving IDPs. We found that
      40% of the complexes possess at least one intermolecular pair of aromatic
      residues. Analysis of composition, characteristics, location and the contribution
      to the free energy of binding showed that pi-pi interactions substantially
      contribute to binding by working as anchor residues, conformational locks, and
      ready-made recognition motifs required for specific binding. By using available
      experimental data we show that pi-pi interactions play a variety of roles that
      link binding of IDPs and their function in the cell. The results presented in
      this study pave the way to understand in atomic detail the inner workings of IDPs
      interaction networks.

PMID- 21863199
TI  - Paramagnetic antibody-modified microparticles coupled with voltammetry as a tool
      for isolation and detection of metallothionen as a bioindicator of metal
      pollution.
AB  - Low-molecular mass proteins rich in cysteines called metallothioneins (MT) can be
      considered as markers for the pollution of the environment by metals. Here, we
      report on suggestion for an automated procedure for the isolation of MT followed
      by voltammetric analysis. Primarily, we optimized the automated detection of MT
      using an electrochemical analyser. It was found that the most sensitive and
      repeatable analyses are obtained at a temperature of 4  degrees C for the
      supporting electrolyte. Further, we optimized experimental conditions for the
      isolation of MT by using antibody-linked paramagnetic microparticles. Under the
      optimal conditions (4 h long interaction between the microparticles and MT), the
      microparticles were tested on isolation of various amounts of MT. The lowest
      isolated amount of MT by antibody-linked paramagnetic microparticles was 5 MUg
      ml(-1) of MT (50 ng). The automated procedure of MT isolation was further tested
      on isolation of MT from guppy fish (Poecilia reticulata) treated with silver(i)
      ions (50 MUM AgNO(3)). The whole process lasted less than five hours and was
      fully automated. We attempted to correlate these results with the standard method
      for MT isolation. The correlation coefficient is 0.9901, which confirms that
      results are in good agreement. Moreover, the concentration of silver ions in
      tissues of fish treated with Ag(i) ions was determined by high performance liquid
      chromatography with electrochemical detection.

PMID- 21863200
TI  - High throughput discovery of heteroaromatic-modifying enzymes allows enhancement
      of novobiocin selectivity.
AB  - Glycosylated analogues of novobiocin, discovered using a broad library of
      enzymes, have 100-fold improved activity against breast, brain, pancreatic, lung
      and ovarian cancers and ablated associated off-target activity leading to an up
      to 2.7 * 10(4) fold increase in selectivity.

PMID- 21863201
TI  - Addiction psychiatry.

PMID- 21863202
TI  - Available resources and human rights -- a South African perspective.

PMID- 21863203
TI  - Dementia in intellectual disability: a review of diagnostic challenges.
AB  - The evaluation of dementia in individuals with intellectual disability (ID),
      which will guide subsequent intervention, care and management depends on the
      systematic review of a number of factors: (1) the individual historical context,
      obtained from multiple sources, (2) evaluation of the pre-existing cognitive,
      behavioural, psychiatric, medical and adaptive skill profile, (3) the
      constellation, and pattern of evolution, of presenting signs and symptoms, (4)
      results of focused investigations, and (5) refinement of the differential
      diagnosis. In patients with ID, standard clinical methods need to be supplemented
      by careful, longitudinal behavioural observations, and individually tailored
      assessment techniques. Co-morbidity, multiple biological, psychological and
      socioenvironmental factors, and complex interactions among events, are the
      reality for many ageing people with ID. Determining the various influences is
      often a formidable clinical task, but should be systematically carried out using
      medical, cognitive, behavioural, neuropsychiatric and psycho-social frameworks.

PMID- 21863204
TI  - Psychological treatments for depression and anxiety disorders in low- and middle-
      income countries: a meta-analysis.
AB  - OBJECTIVE: The objective of this meta-analysis was to determine the efficacy of
      psychological treatments for depression and anxiety disorders in low- and middle-
      income countries (LAMIC). METHOD: Meta-analysis of randomized controlled trials
      on psychological treatment of depression and anxiety disorders in low-and middle
      income countries using an existing database
      (www.evidencebasedpsychotherapies.org), PubMed, Embase, Psychinfo, Dissertation
      Abstracts International and the Cochrane Central Register of Controlled Trials
      were searched for studies published in all languages. Additional studies were
      identified from reference lists of found studies. Randomized controlled trials in
      which a psychological intervention for anxiety or depression was compared to a
      control condition (care-as-usual, waiting list, placebo, or another control
      group) were included. The randomized controlled trials needed to be conducted in
      a LAMI country (classification of LAMI countries according to the World Bank's
      list of economies) to be eligible for inclusion in the meta-analysis.
      Psychological treatments were defined as interventions in which the core element
      of treatment consisted of verbal communication between a therapist and a patient.
      RESULTS: Seventeen studies met our inclusion criteria, with a total of 3,010
      participants. The mean standardized difference between the treatment and control
      groups at post-test was 1.02 (95% CI: 0.76~1.28) which corresponds well with the
      effects found in high-income countries. CONCLUSION: These results indicate that
      psychological treatments of depression and anxiety disorders are also effective
      in LAMI countries, and may encourage global dissemination of these interventions.

PMID- 21863205
TI  - Autism spectrum disorders (ASD) in Africa: a perspective.
AB  - BACKGROUND: The universal occurrence of autism spectrum disorders (ASD) was
      queried about twenty-six years ago. It was thought to occur only in western
      industrialized countries with high technological development. Over the last
      decade, knowledge about ASD and its prevalence has been documented as being on
      the rise in different regions of the world, with most literature coming from the
      western world -- the situation in Africa on aspects of ASD remain unclear.
      METHODS: Literature cited in Pubmed over the last decade on aspects of
      epidemiology, diagnosis, aetiology and knowledge of ASD in the African context
      were assessed. KEYWORDS: autism, diagnosis, aetiology, knowledge and Africa were
      variously combined in the literature search. RESULTS: No study specifically
      addressed the epidemiology of ASD in Africa. One of the two studies that were
      relevant addressed epidemiology of ASD in Arab countries, though included two
      Northern African countries. A higher proportion of non-verbal cases of ASD
      compared to verbal cases was documented in literature coming from Africa.
      Associated co-morbid disorders included intellectual disability, epilepsy and
      oculo-cutaneous albinism. Aetiological factors postulated included post
      encephalitic infection, genetic and auto-immune factors, and vitamin D
      deficiency. Knowledge about ASD in Africa was noted to be low. CONCLUSION: There
      is a need for epidemiological studies in Africa to define the magnitude of the
      problem of ASD and the characteristics of children affected by ASD in this
      region. This would help in planning and might be helpful in answering the
      question of aetiology of ASD. Policy making needs to be directed at issues of
      childhood developmental disorders in Africa.

PMID- 21863206
TI  - The prevalence and correlates of hallucinations in a general population sample:
      findings from the South African Stress and Health Study.
AB  - OBJECTIVE: Large epidemiological surveys conducted in the developed world have
      found rates of psychotic symptoms in the general population to be as high as 10
      28%. However, there are few data available from developing countries, including
      African countries, on the prevalence and correlates of psychotic symptoms. This
      study investigates the prevalence and correlates of psychotic symptoms (ie
      hallucinations) in a general population sample of South African adults. METHOD:
      As part of the South African Stress and Health Study the prevalence of auditory
      and visual hallucinations was determined in a large community based sample of
      4250 participants utilizing the Composite International Diagnostic Interview
      (CIDI). In addition, socio-demographic and clinical correlates as well as
      indicators of service utilization and functional impairment were determined.
      RESULTS: The prevalence of any reported hallucination was 12.7%, a rate
      comparable to that found in studies from the developed world. Multivariate
      analyses revealed a significant association between role impairment, service
      utilisation, suicidality and reported auditory or visual hallucinations. No
      significant association was found between urbanicity and reported psychotic
      symptoms. CONCLUSION: Our finding that psychotic symptoms (ie hallucinations) are
      significantly associated with functional impairment and service utilization
      supports the potential clinical significance of such symptoms, even in the
      African context.

PMID- 21863207
TI  - Anxiety, psychosis and substance use: prevalence, correlates and recognition in
      an outpatient mental health setting.
AB  - OBJECTIVE: The current study examined anxiety in people with substance use
      disorder (SUD) and a psychotic disorder. It is hypothesised that: anxiety
      disorders (AD) would be highly prevalent (greater than 20%) in people identified
      as having SUD and psychotic disorders; those with comorbid AD would fair worse
      than those without, on measures of quality of life, severity of substance
      dependence, locus of control, suicidality and psychotic symptoms; and, the
      presence of such anxiety disorder symptomatology would be under-detected by their
      mental health case managers. METHOD: Outpatients with co-occurring substance use
      disorder and psychosis were interviewed to collect data about their diagnosis,
      depressive and psychotic symptoms, severity of dependence on substances, quality
      of life and locus of control. Participants' case managers made blind ratings of
      the presence and severity of participants' anxiety. RESULTS: Fifty eight percent
      of participants had at least one anxiety disorder. Of these, 56% - 70% had case
      managers who had identified them as having an anxiety problem. The occurrence of
      anxiety disorder was associated with more external locus of control, greater
      intensity of suicidal thinking, worse psychotic symptoms, lower quality of life
      and greater severity of dependence on substances. CONCLUSION: This research
      suggests anxiety in people with substance use disorder and psychosis is highly
      prevalent, is associated with poorer outcomes, and is under detected by case
      managers. Further examination of this issue may lead to important advances in the
      treatment and prognosis of people with substance use disorder and psychosis.

PMID- 21863208
TI  - Knowledge, attitude and practice (KAP) of mental illness among staff in general
      medical facilities in Kenya: practice and policy implications.
AB  - OBJECTIVE: To determine the knowledge, attitudes and beliefs about mental illness
      among staff in general hospitals. METHOD: A descriptive cross-sectional study
      conducted on staff in ten medical facilities in Kenya on their socio-demographic
      characteristics, professional qualifications and knowledge, attitudes and
      practice (KAP) toward mental illness. RESULTS: A total of 684 general hospital
      staff: nurses (47.8%); doctors (18.1%); registered clinical officers (5.1%);
      students (9.5%) and support staff (19.5%) were recruited. About three quarters
      were under 40 years of age; most thought mental illness could be managed in
      general hospital facilities; the older the doctors were (age 40 years and older)
      the more they were aware of and positive towards mental illness. Most of the
      workers did not suspect any psychiatric symptoms among the patients they treated
      resulting in low referral rates for psychiatric services. CONCLUSION: There are
      gaps in knowledge on mental illness which could be constructively filled with
      Continued Medical Education (CME).

PMID- 21863209
TI  - Clozapine-induced pericarditis.
AB  - OBJECTIVE: To report a case of a patient treated with clozapine who developed
      pericarditis with pericardial effusion that resolved when the drug was
      discontinued. METHOD: Case report of a 21-year-old man with psychotic disorder
      that had been stable on clozapine therapy for five months (after failure of
      atypical antipsyhotic agents) presented to the emergency department complaining
      of chest pain and progressive shortness of breath that had lasted for a few days.
      Echocardiography showed a pericardial effusion suggestive of a cardiac tamponade,
      and the fluid was removed by pericardiocentesis. All other possible causes of the
      pericardial effusion were ruled out and clozapine was suspected as the most
      likely explanation. Clozapine was discontinued and the patient's symptoms
      improved markedly. DISCUSSION: According to the Naranjo probability scale,
      clozapine is a probable cause of pericarditis. Although clozapine is a known
      cause of myocarditis and cardiomyopathy, there are only several reports in the
      literature describing clozapine-induced pericarditis and pericardial effusion. In
      our patient, the pericardial effusion cleared within several days following
      clozapine discontinuation. CONCLUSION: There have been only a few cases of
      clozapine-induced pericarditis reported in the literature, however this adverse
      effect of clozapine can occur, as this case report clearly demonstrates. Cardiac
      adverse effects of clozapine are potentially life threatening, hence early
      recognition is essential to prevent serious outcomes.

PMID- 21863210
TI  - Culture, religion and psychosis -- a case study from Limpopo Province, South
      Africa.

PMID- 21863211
TI  - Can we close the barn door before the horses get out? A case study of high
      genetic loading and subsequent development of psychosis.

PMID- 21863212
TI  - Analysis of potential biomarkers and modifier genes affecting the clinical course
      of CLN3 disease.
AB  - Mutations in the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis, a
      pediatric neurodegenerative disorder characterized by visual loss, epilepsy and
      psychomotor deterioration. Although most CLN3 patients carry the same 1-kb
      deletion in the CLN3 gene, their disease phenotype can be variable. The aims of
      this study were to (i) study the clinical phenotype in CLN3 patients with
      identical genotype, (ii) identify genes that are dysregulated in CLN3 disease
      regardless of the clinical course that could be useful as biomarkers, and (iii)
      find modifier genes that affect the progression rate of the disease. A total of
      25 CLN3 patients homozygous for the 1-kb deletion were classified into groups
      with rapid, average or slow disease progression using an established clinical
      scoring system. Genome-wide expression profiling was performed in eight CLN3
      patients with different disease progression and matched controls. The study
      showed high phenotype variability in CLN3 patients. Five genes were dysregulated
      in all CLN3 patients and present candidate biomarkers of the disease. Of those,
      dual specificity phosphatase 2 (DUSP2) was also validated in acutely CLN3
      depleted cell models and in CbCln3(Deltaex7/8) cerebellar precursor cells. A
      total of 13 genes were upregulated in patients with rapid disease progression and
      downregulated in patients with slow disease progression; one gene showed
      dysregulation in the opposite way. Among these potential modifier genes, guanine
      nucleotide exchange factor 1 for small GTPases of the Ras family (RAPGEF1) and
      transcription factor Spi-B (SPIB) were validated in an acutely CLN3-depleted cell
      model. These findings indicate that differential perturbations of distinct
      signaling pathways might alter disease progression and provide insight into the
      molecular alterations underlying neuronal dysfunction in CLN3 disease and
      neurodegeneration in general.

PMID- 21863213
TI  - The p53 upregulated modulator of apoptosis (PUMA) chemosensitizes intrinsically
      resistant ovarian cancer cells to cisplatin by lowering the threshold set by Bcl
      x(L) and Mcl-1.
AB  - Ovarian cancer is the number one cause of death from gynecologic malignancy. A
      defective p53 pathway is a hallmark of ovarian carcinoma. The p53 mutation
      correlates significantly with resistance to platinum-based chemotherapy, early
      relapse and shortened overall survival in ovarian cancer patients. PUMA (p53
      upregulated modulator of apoptosis), a BH3-only Bcl-2 family protein, was
      recently identified as a transcriptional target of p53 and a potent apoptosis
      inducer in various cancer cells. In this study, we showed that the induction of
      PUMA by cisplatin was abolished in p53-deficient SKOV3 cells. Elevated expression
      of PUMA-induced apoptosis and sensitized A2780s and SKOV3 ovarian cancer cells to
      cisplatin, and the combination of PUMA and low-dose cisplatin, significantly
      suppressed xenograft tumor growth in vivo through enhanced induction of apoptosis
      compared with treatment with PUMA or cisplatin alone. The effects of PUMA were
      mediated by enhanced caspase activation and release of cytochrome c and Smac
      (second mitochondria-derived activator of caspase) into the cytosol. Furthermore,
      PUMA chemosensitized intrinsically resistant SKOV3 cells to cisplatin through
      downregulation of B-cell lymphoma-extra large (Bcl-x(L)) and myeloid cell
      leukemia sequence 1 (Mcl-1). PUMA-mediated Bcl-x(L) downregulation mainly
      happened at the transcription level, whereas PUMA-induced Mcl-1 down-regulation
      was associated with caspase-dependent cleavage and proteasome-mediated
      degradation. To our knowledge, these data suggest a new mechanism by which
      overexpression of PUMA enhances sensitivity of SKOV3 cells to cisplatin by
      lowering the threshold set simultaneously by Bcl-x(L) and Mcl-1. Taken together,
      our findings indicate that PUMA is an important modulator of therapeutic
      responses of ovarian cancer cells and is potentially useful as a chemosensitizer
      in ovarian cancer therapy.

PMID- 21863214
TI  - Endoplasmic reticulum stress implicated in the development of renal fibrosis.
AB  - Endoplasmic reticulum (ER) stress-associated apoptosis plays a role in organ
      remodeling after insult. The effect of ER stress on renal tubular damage and
      fibrosis remains controversial. This study aims to investigate whether ER stress
      is involved in tubular destruction and interstitial fibrosis in vivo. Renal cell
      apoptosis was proven by terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) stain and poly-ADP ribose polymerase expression in the
      unilateral ureteral obstruction (UUO) kidney. ER stress was evoked and confirmed
      by the upregulation of glucose-regulated protein 78 (GRP78) and the common Lys
      Asp-Glu-Leu (KDEL) motif of ER retention proteins after UUO. ER stress-associated
      proapoptotic signals, including B-cell chronic lymphocytic leukemia
      (CLL)/lymphoma 2-associated * protein (BAX) expression, caspase-12 and c-Jun N
      terminal kinase (JNK) phosphorylation, were activated in the UUO kidney.
      Prolonged ER stress attenuated both unsplicing and splicing X-box binding protein
      1 (XBP-1) protein expression, but continued to activate inositol-requiring 1alpha
      (IRE1alpha)-JNK phosphorylation, protein kinase RNA-like endoplasmic reticulum
      kinase (PERK), eukaryotic translation initiation factor 2alpha subunit
      (eIF2alpha), activating transcription factor (ATF)-4, CCAAT/enhancer binding
      protein (C/EBP) homologous protein (CHOP) and cleavage activating transcription
      factor 6 (cATF6)-CHOP signals, which induce ER stress-related apoptosis but
      attenuate adaptive unfolded protein responses in UUO kidneys. However, renal
      apoptosis and fibrosis were attenuated in candesartan-treated UUO kidney.
      Candesartan was associated with maintenance of XBP-1 expression and attenuated
      ATF4, cATF6 and CHOP protein expression. Taken together, results show that
      overwhelming ER stress leads to renal cell apoptosis and subsequent fibrosis; and
      candesartan, at least in part, restores renal integrity by blocking ER stress
      related apoptosis. Reducing ER stress may present a way to attenuate renal
      fibrosis.

PMID- 21863215
TI  - Cannabinoid receptor type I modulates alcohol-induced liver fibrosis.
AB  - The cannabinoid system (CS) is implicated in the regulation of hepatic fibrosis,
      steatosis and inflammation, with cannabinoid receptors 1 and 2 (CB1 and CB2)
      being involved in regulation of pro- and antifibrogenic effects. Daily cannabis
      smoking is an independent risk factor for the progression of fibrosis in chronic
      hepatitis C and a mediator of experimental alcoholic steatosis. However, the role
      and function of CS in alcoholic liver fibrosis (ALF) is unknown so far. Thus,
      human liver samples from patients with alcoholic liver disease (ALD) were
      collected for analysis of CB1 expression. In vitro, hepatic stellate cells (HSC)
      underwent treatment with acetaldehyde, Delta9-tetrahydrocannabinol H2O2, endo-
      and exocannabinoids (2-arachidonoylglycerol (2-AG) and [THC]), and CB1 antagonist
      SR141716 (rimonabant). In vivo, CB1 knockout (KO) mice received thioacetamide
      (TAA)/ethanol (EtOH) to induce fibrosis. As a result, in human ALD, CB1
      expression was restricted to areas with advanced fibrosis only. In vitro,
      acetaldehyde, H2O2, as well as 2-AG and THC, alone or in combination with
      acetaldehyde, induced CB1 mRNA expression, whereas CB1 blockage with SR141716
      dose-dependently inhibited HSC proliferation and downregulated mRNA expression of
      fibrosis-mediated genes PCalpha1(I), TIMP-1 and MMP-13. This was paralleled by
      marked cytotoxicity of SR141716 at high doses (5-10 MUmol/L). In vivo, CB1
      knockout mice showed marked resistance to alcoholic liver fibrosis. In
      conclusion, CB1 expression is upregulated in human ALF, which is at least in part
      triggered by acetaldehyde (AA) and oxidative stress. Inhibition of CB1 by
      SR141716, or via genetic knock-out protects against alcoholic-induced fibrosis in
      vitro and in vivo.

PMID- 21863216
TI  - AHR regulates WT1 genetic programming during murine nephrogenesis.
AB  - Mounting evidence suggests that the blueprint of chronic renal disease is
      established during early development by environmental cues that dictate
      alterations in differentiation programming. Here we show that aryl hydrocarbon
      receptor (AHR), a lig-and-activated basic helix-loop-helix-PAS homology domain
      transcription factor, disrupts murine renal differentiation by interfering with
      Wilms tumor suppressor gene (WT1) signaling in the developing kidney. Embryonic
      kidneys of C57BL/6J Ahr-/- mice at gestation d (GD) 14 showed reduced
      condensation in the nephrogenic zone and decreased numbers of differentiated
      structures compared with wild-type mice. These deficits correlated with increased
      expression of the (+) 17aa Wt1 splice variant, decreased mRNA levels of Igf-1
      rec., Wnt-4 and E-cadherin, and reduced levels of 52 kDa WT1 protein. AHR
      knockdown in wild-type embryonic kidney cells mimicked these alterations with
      notable increases in (+) 17aa Wt1 mRNA, reduced levels of 52 kDa WT1 protein, and
      increased (+) 17aa 40-kDa protein. AHR downregulation also reduced Igf-1 rec.,
      Wnt-4, secreted frizzled receptor binding protein-1 (sfrbp-1) and E-cadherin
      mRNAs. In the case of Igf-1 rec. and Wnt-4, genetic disruption was fully reversed
      upon restoration of cellular Wt1 protein levels, confirming that functional
      interactions between AHR and Wt1 represent a likely molecular target for renal
      developmental interference.

PMID- 21863217
TI  - Development of a liposome-based immunochromatographic strip assay for the
      detection of Salmonella.
AB  - Salmonella species are ubiquitous human pathogens which pose a dangerous threat
      to the elderly and children worldwide. In this study, to develop a more efficient
      assay procedure for the rapid detection of Salmonella Typhimurium, an
      immunochromatographic strip assay was developed using immunoliposome (anti
      Salmonella IgG-tagged) encapsulated with sulforhodamine B (SRB). The detection
      sensitivity of the developed immunochromatographic assay was compared with a
      commercial immunochromatographic test strip using colloidal gold nanoparticles.
      The liposomes were prepared through a reverse-phase evaporation method by using a
      lipid and phospholipid mixture and SRB, a fluorescence dye, which was
      encapsulated in the phospholipid bilayer. Furthermore, the outer surface of the
      SRB-encapsulated liposome was conjugated with antibody (affinity-purified
      polyclonal goat anti-Salmonella IgG) to form an immunoliposome (size, 223 nm),
      used as the analytical reagent in the developed immunoassay. For this strip
      assay, a plastic-backed nitrocellulose strip was immobilized with two antibody
      zones. The lower zone of the strip referred to Salmonella antigen capture zone
      (test line), while the other zone served as a positive control (control line).
      The lower zone was coated with affinity-purified polyclonal goat anti-Salmonella
      IgG, while the upper zone was coated with rabbit anti-goat IgG. During capillary
      migration of the wicking solution (diluted liposome and Salmonella culture, each
      50 MUl), Salmonella was captured with surface-bound immunoliposomes at the
      antigen capture zone, while the unbound liposomes migrated upward and bound to
      another zone. The color density of the antigen capture zone was directly
      proportional to the amount of S. Typhimurium in the test sample. As a result, the
      detection limit of the immunochromatographic strip assay developed in this study
      against S. Typhimurium was found to be 10(2) CFU/ml, which was significantly
      higher than the detection limit (10(7) CFU/ml) of the commercial
      immunochromatographic test strip assay.

PMID- 21863218
TI  - Differential expression of miR-144* as a novel fecal-based diagnostic marker for
      colorectal cancer.
AB  - BACKGROUND: MicroRNAs (miRNA) are tiny, noncoding, small, endogenous RNAs that
      play major roles in neoplastic transformation and could therefore offer a better
      quantitative and noninvasive method for the diagnosis and prognosis of colorectal
      cancer (CRC) using feces. In the present study, we screened feces for 648 miRNAs
      and analyzed the role of miR-144* as a potential CRC diagnostic marker. METHODS:
      Fecal miRNA expression was profiled with RT-pre-amplification-qPCR, and the
      stability was determined using both endogenous and exogenous miRNA by RT-qPCR.
      ROC analysis was performed to enhance the diagnosing power of the CRC patients'
      fecal specimens. RESULTS: We detected 39% of all the miRNAs screened in feces.
      Endogenous miRNAs are more stable over time and temperature, while exogenous
      miRNAs degraded rapidly. miR-144* was overexpressed in feces, suggesting that it
      could be a potent candidate diagnostic marker for CRC detection, with a
      sensitivity of 74% and a specificity of 87% (n = 75, p < 0.0001). Moreover, RT
      qPCR analysis showed that miR-144* was also overexpressed in paired CRC tissues,
      thus suggesting its possible utilization as a diagnostic marker. CONCLUSIONS: We
      demonstrated that miRNAs are stable in the fecal microenvironment, and that,
      among them, miR-144* represents a novel fecal-based diagnostic marker for CRC
      screening. Nevertheless, our data need to be validated in a large cohort of
      subjects.

PMID- 21863219
TI  - Lifestyle and psychological factors related to irritable bowel syndrome in
      nursing and medical school students.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal
      disorder comprising abdominal pain, abdominal discomfort, and disordered
      defecation. The prevalence of IBS is 10-15% in the general population. This study
      investigated the prevalence of IBS and the relationship between IBS and stress,
      lifestyle, and dietary habits among nursing and medical school students. METHODS:
      A blank self-administrated questionnaire was used to survey 2,639 students
      studying nursing or medicine. This questionnaire asked about IBS symptoms,
      lifestyle, dietary intake, life events, anxiety, and depression. The
      questionnaires were collected from 2,365 students (89.6%) and the responses of
      1,768 students (74.8%) were analyzed. RESULTS: The prevalence of IBS was 35.5% as
      a whole, 25.2% in males and 41.5% in females. Significantly higher stress scores
      (anxiety and depression) and life events were found in the IBS group than in the
      non-IBS group. Sleep disorders and the time spent sitting were also higher in
      males with IBS. In the IBS group, females ate less fish, fruit, milk, and green
      yellow vegetables, and more processed food products than the non-IBS group (p =
      0.001, p = 0.002, p = 0.032, p = 0.037, p < 0.001). The rates of missed meals and
      irregular mealtimes were significantly higher in females in the IBS group (p =
      0.001, p = 0.013). CONCLUSIONS: The prevalence of IBS was higher among nursing
      and medical students, and further interventional studies are needed to improve
      IBS symptoms.

PMID- 21863220
TI  - Reconsideration of the most appropriate criterion in the lowest classification of
      vision disability in Japan.
AB  - PURPOSE: To verify the current Japanese classification of vision disability in
      regard to visual acuity. METHODS: A questionnaire was sent to 100 ophthalmology
      services in Japan. Each service was asked to extract 300 of their outpatient
      records. From these records, patients who had a sum of corrected visual acuity in
      both eyes of less than or equal to 0.62 were selected for the questionnaire. The
      questionnaire consisted of items related to prevalence, age, sex, with or without
      vision-disabled certification at any grade, the corrected visual acuity of each
      eye and the name of any disease the subject may have had. RESULTS: Sixty-five
      services responded, and, of 20,235 total records reviewed, 971 patients were
      eligible for the questionnaire. The average age was 66.9 +/- 20.0 years, and
      74.6% were over 60 years old. The distribution of corrected visual acuity showed
      three categories. CONCLUSIONS: Our analysis indicates that a new candidate
      criterion for vision-disabled certification is needed for the sixth grade, which,
      at present is defined as, "The sum of the corrected visual acuity of both eyes is
      more than 0.2, but less than or equal to 0.4."

PMID- 21863221
TI  - Relationship between vision-related quality of life and microperimetry-determined
      macular sensitivity in patients with retinitis pigmentosa.
AB  - PURPOSE: The aim of our study was to determine the relationship between vision
      related quality of life (VRQOL) following the National Eye Institute Visual
      Function Questionnaire-25 (NEI VFQ-25) and the macular sensitivity determined by
      microperimetry in patients with retinitis pigmentosa (RP). METHODS: The Japanese
      version of the NEI VFQ-25 was used to assess the VRQOL of 30 patients with
      typical RP whose decimal visual acuity was >=0.6. The mean retinal sensitivity
      within the central 10 degrees  was determined by fundus-related microperimetry
      (MP1). The correlation between the mean of the total composite NEI VFQ-25 score
      and MP1-determined macular sensitivity was determined. RESULTS: Mean NEI VFQ-25
      score was 69.4 +/- 14.5 (range 34.6-90.3) in RP patients. There was a significant
      positive correlation between mean NEI VFQ-25 score and mean retinal sensitivity
      within 10 degrees  (r = 0.673, P = 0.0003). CONCLUSION: The significant
      correlation between macular sensitivity and VRQOL measured with the NEI VFQ-25
      indicates that sensitivity in the macular area is an important consideration in
      using VRQOL with RP patients.

PMID- 21863222
TI  - Hyaluronan production and hyaluronan synthase expression in three human
      conjunctiva-derived cell strains.
AB  - PURPOSE: The conjunctiva maintains the health of the ocular surface by protecting
      the eye from pathogen invasion, injury, and dryness. In this study, we
      investigated the regulation of hyaluronan (HA) synthesis by cytokines in
      conjunctiva-derived cells. METHODS: Cultured primary cells derived from human
      conjunctivas that had been removed as surgical specimens were transfected with an
      immortalizing gene (human papilloma virus 16 E6/E7). To compare the biological
      features of the primary and immortalized cells, we assessed their morphological
      features and gene expression patterns. We also examined the effects of
      inflammatory cytokines on hyaluronan synthase (HAS) expression and HA production.
      RESULTS: Three conjunctiva-derived cell strains were established and could be
      passaged up to 15 times. All strains expressed beta2MG and KRT13 transcripts,
      highly expressed in conjunctival epithelial cells. HA production and expression
      of the three HAS isoforms were detected in the cell strains; however, cytokine
      treatment had no significant effect on HA production or HAS isoform expression.
      CONCLUSIONS: We succeeded in deriving three human cell strains from conjunctival
      tissue. In the conjunctiva-derived cell strains, HA production and HAS mRNA
      expression were stable and were not changed by either TGF-beta or PDGF-BB.

PMID- 21863223
TI  - Natural language processor as a tool to assess heparin induced thrombocytopenia
      awareness.
AB  - The life-threatening consequences of heparin induced thrombocytopenia (HIT) may
      be prevented with early recognition, prompt heparin withdrawal and direct
      thrombin inhibitor use. To determine the level of HIT awareness, electronic term
      recognition software can be used to query the electronic medical record (EMR) to
      assess the thought process and test ordering behavior of health care providers
      confronted with falling platelet counts. We sought to assess the awareness of HIT
      in a large teaching institution using these tools. Mayo Clinic databases were
      queried to identify a cohort of hospitalized adults receiving heparin (06/1/08
      06/1/09). Serial platelet counts for each patient were scrutinized for a 50%
      decrement from baseline. "Clinician awareness" was defined by mention of HIT
      (determined by electronic term recognition software) within the hospital record
      by any member of the healthcare team or requisition of platelet factor 4/heparin
      antibody testing. During this time period, 34,694 adults were hospitalized and
      24,956 received heparin. Only 3,239 (13%) patients had more than 1 platelet count
      during the hospital stay. Of 199 patients (6.1%) with >=50% platelet count drop,
      clinician awareness was 36%. The absolute platelet count was the only independent
      variable associated with HIT awareness (P < 0.001). Both appropriate platelet
      count monitoring and HIT awareness are low at this large teaching institution.
      Software tools for monitoring awareness and providing realtime alerts of
      significant platelet count decrements may be useful.

PMID- 21863224
TI  - The human ileocaecal junction: anatomical evidence of a sphincter.
AB  - PURPOSE: The human ileocaecal junction (ICJ) is a major transition zone
      regulating intestinal transit. Historically, it has often been considered a valve
      rather than a sphincter. The microscopic anatomy of this junction was studied
      searching for evidence of an anatomical sphincter and neuromuscular
      specialisation. METHODS: Ileocaecal specimens were obtained from ten cadavers and
      five surgical donors (7 male, mean age 81 years, age range 68-94) and examined by
      histology and immunohistochemistry. Quantitative analyses of muscle thickness and
      submucosal vascularity were performed together with immunohistochemical studies
      of innervation and the distribution of interstitial cells of Cajal. RESULTS: The
      thickness of the muscular layer in both the ileum and the colon increased
      significantly over a distance of 1 cm leading up to the base of the ileal papilla
      where it reached a maximum (4.19 +/- 2.0 mm) before gradually tapering towards
      the tip of the papilla. Submucosal vascularity in the ileal papilla was not
      increased compared to the adjacent ileum or caecum/colon. Neuronal density was
      less in the caecum and ileal papilla compared to the terminal ileum (P < 0.05).
      Interstitial cells of Cajal were identified within the myenteric plexus of the
      ICJ but their density was similar to the adjacent bowel. CONCLUSIONS: A localised
      muscle thickening at the base of the ileal papilla is consistent with an
      intrinsic anatomical sphincter. There was no evidence that the ICJ has increased
      submucosal vascularity or a greater density of innervation compared to the
      adjacent bowel. The term ileocaecal valve is misleading and should be replaced by
      ileocaecal junction.

PMID- 21863225
TI  - Chordomas of the skull base and cervical spine: clinical outcomes associated with
      a multimodal surgical resection combined with proton-beam radiation in 40
      patients.
AB  - Previous studies of chordoma have focused on either surgery, radiotherapy, or
      particular tumor locations. This paper reviewed the outcomes of surgery and
      proton radiotherapy with various tumor locations. Between 2001 and 2008, 40
      patients with chordomas of the skull base and cervical spine had surgery at our
      hospital. Most patients received proton therapy. Their clinical course was
      reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and
      chondroid appearance were evaluated in regard to the progression-free survival
      (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed
      independently. The extensive resection rate was 42.5%. Permanent neurological
      morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose
      was 68.9 cobalt gray equivalents. The median follow-up was 56.5 months. The 5
      year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in
      12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated
      with a lower PFS (P = 0.007). In the PS group, a younger age and the CCJ location
      were related to a lower PFS (P = 0.008 and P < 0.001, respectively). The CCJ
      location was also related to a lower OS (P = 0.043) and it was more common in
      young patients (P = 0.002). Among the survivors, the median of the last Karnofsky
      Performance Scale score was 80 with 25.7% of patients experiencing an increase
      and 11.4% experiencing a decrease. Multimodal surgery and proton therapy thus
      improved the chordoma treatment. The CCJ location and a younger age are risks for
      disease progression.

PMID- 21863226
TI  - The role of stem cells in fracture healing and nonunion.
AB  - Nonunion and large bone defects present a therapeutic challenge to the surgeon
      and are often associated with significant morbidity. These defects are expensive
      to both the health care system and society. However, several surgical procedures
      have been developed to maximise patient satisfaction and minimise health-care
      associated and socioeconomic costs. Integrating recent evidence into the diamond
      concept leads to one simple conclusion that not only provides us with answers to
      the "open questions" but also simplifies our entire understanding of bone
      healing. It has been shown that a combination of neo-osteogenesis and
      neovascularisation will restore tissue deficits, and that the optimal approach
      includes a biomaterial scaffold, cell biology techniques, a growth factor and
      optimisation of the mechanical environment. Further prospective, controlled,
      randomised clinical studies will determine the effectiveness and economic
      benefits of treatment with mesenchymal stem cells, not in comparison to other
      conventional surgical approaches but in direct conjunction with them.

PMID- 21863227
TI  - Segmental sodium reabsorption by the renal tubule in prenatally programmed
      hypertension in the rat.
AB  - Hypertension and renal dysfunction can be programmed in the rat by prenatal
      exposure to a low-protein (LP) diet. Expression of the renal thick ascending limb
      (TAL) sodium transporter NKCC2 is up-regulated, which has been predicted to
      result in greater sodium reabsorption. However, we have shown that LP rats
      excrete more not less sodium. The aim of this study was to determine whether the
      increased abundance of sodium:potassium:chloride (Na(+):K(+):2Cl(-)) co
      transporter (NKCC2) leads to enhanced sodium uptake by the TAL. Pregnant Wistar
      rats were fed a control (18%) or LP (9%) diet. Amiloride (AM),
      bendroflumethiazide (BF), and furosemide (FUR) were administered acutely to male
      offspring at 4 weeks of age. Fractional excretion of sodium (FE(Na)) was
      significantly greater in vehicle-infused LP rats (3.0 +/- 0.3%) compared with
      controls (1.7 +/- 0.5, P < 0.01). FE(Na) by the LP proximal tubule did not differ
      from controls, whereas FE(Na) by the distal tubule was significantly greater (P <
      0.01). These differences were abolished by the administration of AM + BF
      (equivalent to the outflow from the TAL) and AM + BF + FUR (equivalent to the
      outflow from the proximal tubule), suggesting that the increase in NKCC2
      expression was not functional. However, during acute salt loading, the LP rat
      pressure natriuresis curve was shifted rightward, implying that raised systemic
      blood pressure is required to match urinary sodium excretion with dietary intake.
      These data suggest that renal sodium handling is impaired in the LP rat but that
      this is not due to increased NKCC2 expression.

PMID- 21863228
TI  - Is routine cholecystectomy justified in severely obese patients undergoing a
      laparoscopic Roux-en-Y gastric bypass procedure? A comparative cohort study.
AB  - BACKGROUND: The aim of the present study was to evaluate the risks and benefits
      of concurrent prophylactic cholecystectomy (CPC) during laparoscopic Roux-en-Y
      gastric bypass (LRYGB). METHODS: From December 2000 to November 2006, CPC during
      LRYGB was only performed in the presence of gallbladder pathology (n = 140).
      Beginning in December 2006, CPC was performed during all LRYGB procedures (n =
      134). Exclusion criteria were open bypass procedure, previous bariatric surgery
      other than gastric banding, and previous cholecystectomy (CCE) or necessary
      concurrent CCE due to gallbladder pathology. RESULTS: During a median follow-up
      of 3.1 years, 26 (18.6%; 95% CI, 12.9-25.9%) of 140 patients without CPC
      subsequently required a CCE, leading to a gallbladder disease-free survival rate
      at 5 years of 77.4% (95% CI, 67.3-87.6%). Multivariate analysis identified a
      distal LRYGB and excess weight loss of >75% at 2 years to be significant risk
      factors for the development of biliary complications while a preoperative BMI >
      50 m(2)/kg was protective. In the second series, prophylactic CCE was not
      associated with prolonged hospitalization or operative time. The postoperative
      complications were not related to the CPC. CONCLUSIONS: The present data indicate
      that a substantial number of patients develop gallbladder complications after
      LRYGB. Furthermore, CPC can safely be performed during LRYGB. Based on these
      findings, CPC should be considered a reasonable approach in severely obese
      patients undergoing LRYGB.

PMID- 21863229
TI  - The digastric muscle is less involved in pharyngeal swallowing in rabbits.
AB  - The swallowing reflex is centrally programmed by the lower brain stem, the so
      called swallowing central pattern generator (CPG), and once the reflex is
      initiated, many muscles in the oral, pharyngeal, laryngeal, and esophageal
      regions are systematically activated. The mylohyoid (MH) muscle has been
      considered to be a "leading muscle" according to previous studies, but the
      functional role of the digastric (DIG) muscle in the swallowing reflex remains
      unclear. In the present study, therefore, the activities of single units of MH
      and DIG neurons were recorded extracellularly, and the functional involvement of
      these neurons in the swallowing reflex was investigated. The experiments were
      carried out on eight adult male Japanese white rabbits anesthetized with
      urethane. To identify DIG and MH neurons, the peripheral nerve (either DIG or MH)
      was stimulated to evoke action potentials of single motoneurons. Motoneurons were
      identified as such if they either (1) responded to antidromic nerve stimulation
      of DIG or MH in an all-or-none manner at threshold intensities and (2) followed
      stimulation frequencies of up to 0.5 kHz. As a result, all 11 MH neurons recorded
      were synchronously activated during the swallowing reflex, while there was no
      activity in any of the 7 DIG neurons recorded during the swallowing reflex. All
      neurons were anatomically localized ventromedially at the level of the caudal
      portion of the trigeminal motor nucleus, and there were no differences between
      the MH and DIG neuron sites. The present results strongly suggest that at least
      in the rabbit, DIG motoneurons are not tightly controlled by the swallowing CPG
      and, hence, the DIG muscle is less involved in the swallowing reflex.

PMID- 21863230
TI  - The non-protein amino acid beta-N-methylamino-L-alanine in Portuguese
      cyanobacterial isolates.
AB  - The tailor made amino acid beta-N-methyl-amino-L-alanine (BMAA) is a neurotoxin
      produced by cyanobacteria. It has been associated with certain forms of
      progressive neurodegenerative disease, including sporadic Amyotrophic Lateral
      Sclerosis and Alzheimer's disease. Some different reports of BMAA in
      cyanobacterial blooms from lakes, reservoirs, and other water resources have been
      made by different investigators. We here report the detection of BMAA of both
      free and protein-bound produced by cyanobacteria, belonging to the Chroococcales,
      Oscillatoriales and Nostocales ordered. We use a rapid and sensitive HPLC-FD
      method that utilizes methanol elution and the Waters AQC Tag chemistry. On other
      hand, we have used three different assay procedures for BMAA extraction from
      cyanobacteria: Trichloroacetic acid (TCA), Methanol/Acetone and hydrochloric acid
      (HCl). All assays let successfully detect BMAA in all cyanobacteria samples
      analyzed. Nevertheless, with TCA and HCl extraction procedures the highest BMAA
      values, for free as well as protein-bound BMAA were detected. BMAA content could
      not be related to the taxonomy of the isolates or to their geographical origin,
      and no correlation between free and protein-bound BMAA concentrations were
      observed within or between taxonomic groups. These data offer confirmation of the
      taxonomic and geographic ubiquity of BMAA from naturally occurring populations of
      cyanobacteria, for the first time reported for estuaries.

PMID- 21863231
TI  - Concluding remarks.

PMID- 21863232
TI  - Increased thermostability of microbial transglutaminase by combination of several
      hot spots evolved by random and saturation mutagenesis.
AB  - The thermostability of microbial transglutaminase (MTG) of Streptomyces
      mobaraensis was further improved by saturation mutagenesis and DNA-shuffling.
      High-throughput screening was used to identify clones with increased
      thermostability at 55 degrees C. Saturation mutagenesis was performed at seven
      "hot spots", previously evolved by random mutagenesis. Mutations at four
      positions (2, 23, 269, and 294) led to higher thermostability. The variants with
      single amino acid exchanges comprising the highest thermostabilities were
      combined by DNA-shuffling. A library of 1,500 clones was screened and variants
      showing the highest ratio of activities after incubation for 30 min at 55 degrees
      C relative to a control at 37 degrees C were selected. 116 mutants of this
      library showed an increased thermostability and 2 clones per deep well plate were
      sequenced (35 clones). 13 clones showed only the desired sites without additional
      point mutations and eight variants were purified and characterized. The most
      thermostable mutant (triple mutant S23V-Y24N-K294L) exhibited a 12-fold higher
      half-life at 60 degrees C and a 10-fold higher half-life at 50 degrees C compared
      to the unmodified recombinant wild-type enzyme. From the characterization of
      different triple mutants differing only in one amino acid residue, it can be
      concluded that position 294 is especially important for thermostabilization. The
      simultaneous exchange of amino acids at sites 23, 24, 269 and 289 resulted in a
      MTG-variant with nearly twofold higher specific activity and a temperature
      optimum of 55 degrees C. A triple mutant with amino acid substitutions at sites
      2, 289 and 294 exhibits a temperature optimum of 60 degrees C, which is 10
      degrees C higher than that of the wild-type enzyme.

PMID- 21863233
TI  - Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in
      Long-Evans rats by the alpha-2 adrenoreceptor antagonist yohimbine.
AB  - RATIONALE: Developing models to efficiently explore the mechanisms by which
      stress can mediate reinstatement of drug-seeking behavior is crucial to the
      development of new pharmacotherapies for alcohol use disorders. OBJECTIVES: We
      examined the effects of multiple reinstatement sessions using the pharmacological
      stressor, yohimbine, in ethanol- and sucrose-seeking rats in order to develop a
      more efficient model of stress-induced reinstatement. METHODS: Long-Evans rats
      were trained to self-administer 10% ethanol with a sucrose-fading procedure, 20%
      ethanol without a sucrose-fading procedure, or 5% sucrose in 30-min operant self
      administration sessions, followed by extinction training. After reaching
      extinction criteria, the animals were tested once per week with yohimbine vehicle
      and yohimbine (2 mg/kg), respectively, 30 min prior to the reinstatement sessions
      or blood collection. Levels of reinstatement and plasma corticosterone (CORT)
      were determined each week for four consecutive weeks. RESULTS: Yohimbine induced
      reinstatement of ethanol- and sucrose-seeking in each of the 4 weeks.
      Interestingly, the magnitude of the reinstatement decreased for the 10% ethanol
      group after the first reinstatement session but remained stable for the 20%
      ethanol group trained without sucrose. Plasma CORT levels in response to
      injection of both vehicle and yohimbine were significantly higher in the ethanol
      trained animals compared to sucrose controls. CONCLUSIONS: The stable
      reinstatement in the 20% ethanol group supports the use of this training
      procedure in studies using within-subject designs with multiple yohimbine
      reinstatement test sessions. Additionally, these results indicate that the
      hormonal response to stressors can be altered following extinction from self
      administration of relatively modest amounts of ethanol.

PMID- 21863234
TI  - Disulfiram stimulates dopamine release from noradrenergic terminals and
      potentiates cocaine-induced dopamine release in the prefrontal cortex.
AB  - RATIONALE: Disulfiram efficacy in treatment of cocaine addiction is attributed to
      the inhibition of dopamine-beta-hydroxylase and reduction in brain noradrenaline
      (NA)/dopamine (DA) ratio. OBJECTIVES: Using microdialysis, we investigated if
      disulfiram causes DA release from noradrenergic terminals and modifies cocaine
      induced DA release. RESULTS: Disulfiram reduced extracellular NA in the medial
      prefrontal (mPF) cortex, occipital cortex, accumbens and caudate nuclei, while it
      markedly increased DA not only in mPF but also in the occipital cortex, despite
      its scanty dopaminergic afferences, and modestly increased DA in the accumbens
      and caudate nuclei, despite their dense dopaminergic innervation. Disulfiram
      induced DA accumulation was reversed in both cortices by tetrodotoxin infusion
      and by systemic administration of the alpha(2)-adrenoceptor agonist clonidine,
      but was not modified by the alpha(2)-adrenoceptor antagonist RS 79948 or the D(2)
      like agonist quinpirole. Disulfiram prevented cocaine-induced NA release in the
      mPF cortex and nucleus accumbens, potentiated cocaine-induced DA release in the
      mPF cortex but failed to modify cocaine effect in the nucleus accumbens. DA
      release induced by disulfiram-cocaine combination in the mPF cortex was prevented
      by clonidine but not by quinpirole. CONCLUSIONS: We suggested that disulfiram, by
      removing NA-mediated inhibitory control on noradrenergic terminals, causes an
      unrestrained cocaine-induced DA release from those terminals in the mPF cortex.
      In the accumbens and caudate nuclei, "allogenic" DA concentration might be
      clouded by DA originated from dopaminergic terminals. The possible role of
      "allogenic" DA in disulfiram ability to prevent stress-induced reinstatement of
      cocaine seeking is discussed.

PMID- 21863235
TI  - Pre-treatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced
      impulsive responding and regional c-Fos protein expression.
AB  - RATIONALE: Overactivation of serotonin (5-hydroxytryptamine, 5-HT)(2A) receptors
      causes impulsivity and attentional deficits. Since 5-HT(2A) receptors are known
      to entertain antagonistic interactions with metabotropic glutamate (mGlu)2/3
      receptors, this interaction may provide an alternative target for a novel class
      of antipsychotics. OBJECTIVES/METHODS: The study characterizes interactions
      between 5-HT(2A) and mGlu2/3 receptors implicated in impulse control. Hooded
      Lister rats were trained in a 5-choice serial reaction time task (5-CSRTT) and
      treated with the 5-HT(2A/2C) receptor agonist (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropan hydrochloride (DOI, 0.1 mg/kg) and the mGlu2/3 receptor
      agonist LY379268 (1 mg/kg). In addition, associated drug-induced changes in
      neuronal activity were assessed via c-Fos immunoreactivity (Fos IR), and co
      localization of c-Fos and GABAergic markers was detected using double
      immunofluorescence labeling. RESULTS: Systemic DOI caused impulsive
      overresponding that was attenuated in animals pre-treated with LY379268. LY379268
      itself had no significant effect on the rats' performance in the 5-CSRTT. DOI
      enhanced Fos IR within fronto-cortical and limbic brain structures, and this
      effect was blocked by LY379268 pre-treatment. Double immunofluorescence labeling
      showed a specific co-localization of DOI-elicited Fos IR with GABAergic (GAD(67)
      positive) cells lacking the calcium-binding protein parvalbumin while LY379268
      increased Fos IR in GABAergic and non-GABAergic cells. CONCLUSION: Our results
      suggest that impulsivity is possibly due to a primary increase in Glu
      transmission mediated via 5-HT(2A) receptor activation. Thus, mGlu2/3 receptor
      agonists might have some potential for treating motor impulsivity-related
      impairments while their cognitive enhancing effects were not confirmed in this
      study.

PMID- 21863236
TI  - Acquisition of cocaine self-administration in male Sprague-Dawley rats: effects
      of cocaine dose but not initial locomotor response to cocaine.
AB  - RATIONALE: We have previously described a model in which adult outbred male
      Sprague-Dawley rats are classified as either low or high cocaine responders (LCRs
      or HCRs, respectively) based on acute cocaine-induced open-field activation. This
      model revealed important individual differences in cocaine's effects, including
      that LCRs exhibited greater responding than HCRs on a progressive ratio schedule
      of cocaine reinforcement. However, no LCR/HCR differences in acquisition of
      cocaine self-administration (0.25 mg/kg/12 s infusion) were observed under these
      conditions. OBJECTIVES: To determine if LCRs and HCRs differ in the effectiveness
      of cocaine to function as a reinforcer under a broader range of conditions, the
      present study assessed the acquisition of cocaine self-administration (fixed
      ratio 1 schedule of reinforcement) as a function of i.v. cocaine dose (0.1875,
      0.375, 0.5, 1, or 1.5 mg/kg/6 s infusion). RESULTS: LCRs and HCRs did not differ
      significantly on any measure of acquisition examined, including the day to meet
      acquisition criterion, percent acquired, and cocaine intake. The effect of dose
      on percent acquired and rate of acquisition peaked at the 1-mg/kg/infusion dose
      of cocaine. In contrast, the effect of dose on cocaine intake was linear, with
      the highest rate of intake occurring at the 1.5-mg/kg/infusion dose of cocaine.
      CONCLUSIONS: LCRs and HCRs do not appear to differ in their acquisition of
      cocaine-reinforced operant responding across a range of cocaine doses, including
      conditions that lead to high levels of cocaine intake.

PMID- 21863237
TI  - A phase I trial of PX-12, a small-molecule inhibitor of thioredoxin-1,
      administered as a 72-hour infusion every 21 days in patients with advanced
      cancers refractory to standard therapy.
AB  - PURPOSE: This phase I trial assessed the safety, dose limiting toxicity (DLT) and
      pharmacodynamics of PX-12 in adult patients with advanced refractory cancers.
      METHODS: PX-12 was administered to sequential cohorts as a 72-h infusion
      utilizing a portable infusion pump on days 1, 2, and 3 of a 21-day cycle at a
      starting dose level of 300 mg/m(2)/day and escalating dose levels till DLT was
      observed. Plasma thioredoxin (Trx-1), vascular endothelial growth factor (VEGF)
      and FGF-2 (fibroblast growth factor) levels were measured predose and during
      infusion of PX-12. RESULTS: Patients (n = 14) were enrolled to the following dose
      cohorts, 300 mg/m(2) (n = 3), 400 mg/m(2) (n = 10) and 500 mg/m(2) (n = 1).
      Common grade 1/2 toxicities included fatigue, taste alteration and odor caused by
      expired drug metabolite. DLTs were one episode each of grade 3 hypoxia at the 400
      mg/m(2) and grade 3 reversible pneumonitis at the 500 mg/m(2) dose levels. Best
      response was stable disease in a patient with rectal cancer. Predose Trx-1 levels
      (n = 12) ranged from 5.1 to 30.0 ng/mL (median 12.6 ng/mL). CONCLUSION: PX-12
      administered at 400 mg/m(2)/day by 72-hour infusion appears safe and tolerable.
      Inhibition of thioredoxin is a strategy worth evaluation with next generation of
      inhibitors.

PMID- 21863238
TI  - A phase II trial of gefitinib for recurrent or metastatic cancer of the esophagus
      or gastroesophageal junction.
AB  - BACKGROUND: Conventional chemotherapeutic agents are of limited benefit in
      patients with recurrent or metastatic cancer of the esophagus or gastroesophageal
      junction (GEJ). We report results from a phase II trial in this population using
      gefitinib, an oral epidermal growth factor receptor inhibitor. PATIENTS AND
      METHODS: Eligibility required a diagnosis of esophageal or GEJ adenocarcinoma or
      squamous cell carcinoma, which was either metastatic or recurrent and incurable
      after initial therapy. No more than one prior chemotherapy regimen was permitted.
      Treatment consisted of gefitinib 250 mg daily for a minimum of 8 weeks. RESULTS:
      Between April 2003 and January 2010, 58 patients, including 18 who were
      chemotherapy-naive, were entered into this trial. Toxicity was modest, although
      most experienced grade 1-2 diarrhea and/or skin rash. There were 4 partial
      responders (7%) and 10 patients with stable disease (17%). The clinical benefit
      (partial response and stable disease) lasted for a median 6.1 months. Median
      survival for all patients was 5.5 months with survival projections at 1-year of
      24.6% and at 2-years of 12.5%. CONCLUSION: Gefitinib was well tolerated but of
      limited efficacy in patients with recurrent or metastatic esophageal or GEJ
      cancer. Further study of this or similar agents will require better patient
      selection.

PMID- 21863239
TI  - Association of bronchopulmonary dysplasia and hypercarbia in ventilated infants
      with birth weights of 500-1,499 g.
AB  - Bronchopulmonary dysplasia (BPD) continues to be a major pulmonary complication
      in very low birth weight (VLBW) and extremely low birth weight (ELBW) survivors
      of neonatal intensive care units (NICUs). Many factors including partial
      pressures of carbon dioxide (PaCO: (2)) have been implicated as possible causes.
      Permissive hypercapnia has become a more common practice in ventilated infants,
      but its effect on BPD is unclear. The hypothesis of this study was that
      hypercarbia is associated with increased BPD in infants with birth weights of 500
      1,499 g. Nine hospitals were involved in this observational cohort study.
      Maternal and infant information including socio-demographics, antenatal steroids,
      gender, race, gestational age, birth weight, intubation and ventilator status,
      physiologic variables and data on therapies were collected by chart abstraction.
      SNAP scores were assigned. Candidate BPD risk factors, including cumulative
      exposures derived from blood gas and ventilation data in the first 6 days of
      life, were identified. Risk models were developed for 425 preterm infants who
      survived to 36 weeks post-menstrual age. BPD occurrence was associated with the
      cumulative burden of MAP >0 cm H(2)O in the first 6 days of life (P < 0.0001).
      After adjustment for the burden of MAP, the occurrence of hypercarbia (PaCO: (2)
      >50 torr) was associated with a greater incidence of BPD (P = 0.024). Among 293
      intubated, mechanically ventilated infants, those with hypercarbia occurring only
      when MAP <= 8 cm H(2)O, a scenario more comparable to permissive hypercapnia,
      also had increased BPD incidence compared to infants without hypercarbia (P =
      0.0003). Hypercarbia during the first 6 days of life was associated with
      increased incidence of BPD in these infants. Mechanically ventilated infants with
      hypercarbia during low MAP also had a significant increase in BPD. Permissive
      hypercapnia in ventilated infants needs further close review before the practice
      becomes even more widespread.

PMID- 21863240
TI  - Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and
      survival of prostate cancer cells treated with diallyl trisulfide.
AB  - PURPOSE: In our previous study, we demonstrated that diallyl trisulfide (DATS)
      induced iron-dependent G2-M arrest of prostate cancer cell cycle. Moreover,
      ferritin degradation and an increase of labile iron pool has been linked to the
      activation of the JNK signaling axis. In the present work, we extended this study
      to determine which of the c-jun kinases is responsible for ferritin degradation
      and the role of iron in DATS-induced cell death. We hypothesized that JNK1
      activates Itch ligase which will lead to ferritin ubiquitination, an increase in
      iron-dependent ROS formation and cell death. METHODS: PC-3 prostate cancer cells
      were used in this study. Cell viability, concentration of ROS, labile iron pool,
      and changes in ferritin and P-Itch and DNA damage were determined. RESULTS: We
      observed that DATS induced ferritin degradation through JNK, Itch signaling axis.
      DATS did not induce neither ROS formation nor increase the LIP in JNK1-DN
      transfected cells. We also observed that DATS increased JNK-dependent activating
      phosphorylation of E3ligase Itch. The cells transfected with inactive form of
      Itch were more resistant against cytotoxicity of DATS and showed lower DATS
      induced ferritin degradation. Desferrioxamine a specific iron chelator had no
      effect neither on cell viability nor DNA damage evaluated by comet assay.
      CONCLUSIONS: These results suggest that JNK1-dependent increase in LIP is
      mediated by Itch ubiquitin ligase.

PMID- 21863241
TI  - Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human
      aortic endothelial cells.
AB  - BACKGROUND: Altered expression of cell adhesion molecules (CAMs) has been
      implicated in a variety of chronic inflammatory conditions, including
      atherosclerosis. Regulation of adhesion molecule expression by specific redox
      sensitive mechanisms has been reported. Additionally, it has been observed that
      the extract of Aronia melanocarpa (A. Melanocarpa) fruits, rich in polyphenols,
      exhibits potent anti-oxidant properties and displays cardioprotective activity.
      METHODS AND RESULTS: Human aortic endothelial cells (HAECs) were pretreated with
      various concentrations (primarily 50 MUg/mL) of Aronia Melanocarpa fruit extract
      prior to treatment with TNFalpha (10 ng/mL) for various periods of time. The
      surface protein and mRNA expression of ICAM-1 and VCAM-1 were determined using
      flow cytometry and real-time RT-PCR, respectively. Adhesion of peripheral blood
      mononuclear leucocytes (PBMLs) to TNFalpha-treated HAECs was evaluated by an
      adhesion assay. Activation of NF-kappaB was evaluated by measuring NF-kappaB p65
      phosphorylation using flow cytometry. ROS production was determined by reduction
      in fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). Tested A.
      Melanocarpa extract significantly inhibited the expression of ICAM-1 and VCAM-1,
      attenuated the phosphorylation of NF-kappaB p65 and decreased intracellular ROS
      production in TNFalpha-treated HAECs. CONCLUSION: We conclude that A. Melanocarpa
      fruit extract exhibits anti-inflammatory effects in HAECs by inhibiting the
      expression of endothelial CAMs, activation of NF-kappaB and production of ROS.

PMID- 21863243
TI  - A novel human high-risk ependymoma stem cell model reveals the differentiation
      inducing potential of the histone deacetylase inhibitor Vorinostat.
AB  - Incompletely resectable ependymomas are associated with poor prognosis despite
      intensive radio- and chemotherapy. Novel treatments have been difficult to
      develop due to the lack of appropriate models. Here, we report on the generation
      of a high-risk cytogenetic group 3 and molecular group C ependymoma model (DKFZ
      EP1NS) which is based on primary ependymoma cells obtained from a patient with
      metastatic disease. This model displays stem cell features such as self-renewal
      capacity, differentiation capacity, and specific marker expression. In vivo
      transplantation showed high tumorigenic potential of these cells, and xenografts
      phenotypically recapitulated the original tumor in a niche-dependent manner. DKFZ
      EP1NS cells harbor transcriptome plasticity, enabling a shift from a neural stem
      cell-like program towards a profile of primary ependymoma tumor upon in vivo
      transplantation. Serial transplantation of DKFZ-EP1NS cells from orthotopic
      xenografts yielded secondary tumors in half the time compared with the initial
      transplantation. The cells were resistant to temozolomide, vincristine, and
      cisplatin, but responded to histone deacetylase inhibitor (HDACi) treatment at
      therapeutically achievable concentrations. In vitro treatment of DKFZ-EP1NS cells
      with the HDACi Vorinostat induced neuronal differentiation associated with loss
      of stem cell-specific properties. In summary, this is the first ependymoma model
      of a cytogenetic group 3 and molecular subgroup C ependymoma based on a human
      cell line with stem cell-like properties, which we used to demonstrate the
      differentiation-inducing therapeutic potential of HDACi.

PMID- 21863242
TI  - Expression of the progenitor marker NG2/CSPG4 predicts poor survival and
      resistance to ionising radiation in glioblastoma.
AB  - Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond
      poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of
      radioresistance are not completely understood. However, cancer cells with an
      immature stem-like phenotype are hypothesised to play a role in radioresistance.
      Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate
      several aspects of GBM progression in experimental systems, we hypothesised that
      its expression would influence the survival of GBM patients. Quantification of
      NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients
      revealed that 50% express high NG2 levels on tumour cells and associated vessels,
      being associated with significantly shorter survival. This effect was independent
      of age at diagnosis, treatment received and hypermethylation of the O(6)
      methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was
      frequently co-expressed with nestin and vimentin but rarely with CD133 and the
      NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D
      proteomics of 11 randomly selected biopsies revealed upregulation of an
      antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients.
      Expression of PRDX-1 was associated with significantly reduced products of
      oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to
      ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle
      checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates
      and sensitised them to IR in vivo. Our data establish NG2 as an important
      prognostic factor for GBM patient survival, by mediating resistance to
      radiotherapy through induction of ROS scavenging enzymes and preferential DNA
      damage signalling.

PMID- 21863244
TI  - Trade-offs of host use between generalist and specialist Helicoverpa sibling
      species: adult oviposition and larval performance.
AB  - Much attention has been paid to the question of the relative importance of female
      behaviour versus larval feeding capacities in determining the host range of
      herbivorous insects. Host-use trade-offs displayed by generalist and specialist
      sister species of the genus Helicoverpa were evaluated to examine the
      relationship between maternal choice and offspring performance. The prediction of
      optimal oviposition theory, that females will choose to lay eggs on plants on
      which their offspring perform best as larvae, was tested by measuring oviposition
      preference and larval performance of Helicoverpa armigera and H. assulta on
      tobacco, sunflower, and hot pepper. These two measures were more highly
      correlated in the specialist H. assulta. Both species exhibited the same
      oviposition preference ranking: tobacco > sunflower > hot pepper. H. armigera
      larvae preferred sunflower, followed by tobacco and hot pepper; while H. assulta
      larvae preferred tobacco to sunflower and hot pepper, consistent with their
      mothers' oviposition preference. Duration of the total period from egg to adult
      emergence for each species was significantly shorter on the host plant preferred
      by the larvae. H. assulta had shorter larval duration and higher relative growth
      rate than H. armigera on tobacco and hot pepper, and vice versa for sunflower,
      indicating species differences in host utilization. Thus, while only the
      specialist H. assulta displayed the predicted optimal oviposition pattern,
      females of both species show the least preference for the plant on which their
      offspring perform worst. Selection for optimal oviposition may be stronger on the
      specialist, which has fewer choices and lower lifetime fecundity than the
      generalist.

PMID- 21863245
TI  - Scale-dependent segregation of seeders and resprouters in cork oak (Quercus
      suber) forests.
AB  - Recent studies showed that disturbances and water availability determine the
      richness among plants with different post-fire strategies of Mediterranean-type
      ecosystems. The aim of this study was to determine whether or not the scale of
      analysis has an influence on the effects of these factors and, therefore, on the
      segregation of the dominant post-fire strategies, obligate seeders and obligate
      resprouters, and facultative species. We recorded all woody species and
      geographical features on 94 (75 m(2)) plots of cork oak woodlands in the southern
      Iberian Peninsula. For each regenerative type (resprouters, seeders and species
      with both traits--facultative species), we tested the relationship between the
      number of species and the predictors using a generalised linear mixed model. The
      fixed predictor considered at the large scale was altitude, and fixed predictors
      considered at the local scale were aspect (north/south) and disturbance (fire and
      clearing by heavy machinery; yes/no). The random predictor was the factor of
      site. When this factor did not have significant effect for some regenerative
      types, these relationships was tested using a generalised linear model.
      Resprouting species were most represented at lower altitudes and in undisturbed
      sites, while seeders were also at lower altitudes but mostly on south-facing
      slopes, especially south-facing disturbed sites. For facultative species, site is
      the most important variable. The proportion of seeders from the total species is
      not related to altitude, but it is related to disturbance and aspect. These
      results suggest that there is no segregation of the richness of seeders and
      resprouters at the large scale (altitudinal gradient). Differences appeared at
      the local scale (aspect and disturbance).

PMID- 21863246
TI  - Large grazers modify effects of aboveground-belowground interactions on small
      scale plant community composition.
AB  - Aboveground and belowground organisms influence plant community composition by
      local interactions, and their scale of impact may vary from millimeters
      belowground to kilometers aboveground. However, it still poorly understood how
      large grazers that select their forage on large spatial scales interact with
      small-scale aboveground-belowground interactions on plant community
      heterogeneity. Here, we investigate how cattle (Bos taurus) modify the effects of
      interactions between yellow meadow ants (Lasius flavus) and European brown hares
      (Lepus europaeus) on the formation of small-scale heterogeneity in vegetation
      composition. In the absence of cattle, hares selectively foraged on ant mounds,
      while under combined grazing by hares and cattle, vertebrate grazing pressure was
      similar on and off mounds. Ant mounds that were grazed by only hares had a
      different plant community composition compared to their surroundings: the cover
      of the grazing-intolerant grass Elytrigia atherica was reduced on ant mounds,
      whereas the relative cover of the more grazing-tolerant and palatable grass
      Festuca rubra was enhanced. Combined grazing by hares and cattle, resulted in
      homogenization of plant community composition on and off ant mounds, with high
      overall cover of F. rubra. We conclude that hares can respond to local ant-soil
      vegetation interactions, because they are small, selective herbivores that make
      their foraging decisions on a local scale. This results in small-scale plant
      patches on mounds of yellow meadow ants. In the presence of cattle, which are
      less selective aboveground herbivores, local plant community patterns triggered
      by small-scale aboveground-belowground interactions can disappear. Therefore,
      cattle modify the consequences of aboveground-belowground interactions for small
      scale plant community composition.

PMID- 21863247
TI  - Muscle-specific growth hormone receptor (GHR) overexpression induces hyperplasia
      but not hypertrophy in transgenic zebrafish.
AB  - Even though growth hormone (GH) transgenesis has demonstrated potential for
      improved growth of commercially important species, the hormone excess may result
      in undesired collateral effects. In this context, the aim of this work was to
      develop a new model of transgenic zebrafish (Danio rerio) characterized by a
      muscle-specific overexpression of the GH receptor (GHR) gene, evaluating the
      effect of transgenesis on growth, muscle structure and expression of growth
      related genes. In on line of transgenic zebrafish overexpressing GHR in skeletal
      muscle, no significant difference in total weight in comparison to non
      transgenics was observed. This can be explained by a significant reduction in
      expression of somatotrophic axis-related genes, in special insulin-like growth
      factor I (IGF-I). In the same sense, a significant increase in expression of the
      suppressors of cytokine signaling 1 and 3 (SOCS) was encountered in transgenics.
      Surprisingly, expression of genes coding for the main myogenic regulatory factors
      (MRFs) was higher in transgenic than non-transgenic zebrafish. Genes coding for
      muscle proteins did not follow the MRFs profile, showing a significant decrease
      in their expression. These results were corroborated by the histological
      analysis, where a hyperplasic muscle growth was observed in transgenics. In
      conclusion, our results demonstrated that GHR overexpression does not induce
      hypertrophic muscle growth in transgenic zebrafish probably because of SOCS
      impairment of the GHR/IGF-I pathway, culminating in IGF-I and muscle proteins
      decrease. Therefore, it seems that hypertrophy and hyperplasia follow two
      different routes for entire muscle growth, both of them triggered by GHR
      activation, but regulated by different mechanisms.

PMID- 21863248
TI  - Molecular characterizations of Nop16 in murine mammary tumors with varying levels
      of c-Myc.
AB  - NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated
      gene in in vitro studies, hence coexpression levels were strongly correlated.
      Importantly, high expression of NOP16 was associated with poor clinical outcome
      in breast cancer patients. However, coexpression of NOP16, MYC and estrogen
      receptor (ESR1) varied widely in tumors and cell lines suggesting that
      transcriptional regulation differed according to pathological environments. The
      goal of this study was to determine the expression patterns of Nop16, Myc and
      Esr1 in murine mammary tumors with disparate histopathological and molecular
      features. We hypothesized that tumor environments with relatively high Myc levels
      would have different coexpression patterns than tumor environments with
      relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein
      in tumors from WAP-c-myc mice that were of high grade and metastasized
      frequently. In contrast, Myc and Nop16 mRNA and proteins levels were
      significantly lower in the less aggressive tumors that developed in NRL-TGFalpha
      mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1
      mRNA levels correlated positively with Myc levels in both models. However, Myc
      and Nop16 transcript levels correlated positively only in tumors from NRL
      TGFalpha mice. We identified prominent NOP16 protein in nuclei and less prominent
      staining in the cytoplasm of luminal cells of ducts and lobules from normal
      mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFalpha
      mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear
      staining was faint or absent and cytoplasmic staining more pronounced. In
      summary, the regulation of expression and localization of NOP16 varies in tumor
      environments with high versus low MYC levels and demonstrate the importance of
      stratifying clinical breast cancers based on MYC levels.

PMID- 21863249
TI  - Dual anca positivity in a child with moyamoya-like cerebral vascular changes: an
      unusual presentation with sudden homonymous hemianopsia.
AB  - A 12-year-old girl presented with a sudden decrease in her right visual acuity
      and homonymous hemianopsia. An angiography of the retinal arteries demonstrated
      recanalized occlusion of the right retinal artery. Cerebral angiography showed
      bilateral internal carotid artery stenosis associated with the development of
      collateral circulation. Laboratory evaluations revealed dual antineutrophil
      cytoplasmic antibodies (ANCA) positivity [anti-proteinase (anti-PR3) ANCA and
      anti-myeloperoxidase (anti-MPO) ANCA], anticardiolipin (aCL) antibodies, and low
      titers of antinuclear antibodies (ANA). There was no evidence of active systemic
      lupus erythematosus (SLE), ANCA-related vasculitis, or other risk factors for
      cerebral occlusion, such as antiphospholipid syndrome (APS). Dual positivity for
      both cytoplasmic (c-ANCA) and perinuclear (p-ANCA) antineutrophil antibodies has
      been found previously in a small number of reports, but to our knowledge, this
      case represents the first case of moyamoya disease associated with dual ANCA
      positivity.

PMID- 21863250
TI  - Cytokinin-induced VvTFL1A expression may be involved in the control of grapevine
      fruitfulness.
AB  - Grapevine bud fruitfulness is determined by the differentiation of uncommitted
      meristem (UCM) into either tendril or inflorescence. Since tendril and
      inflorescence differentiation have long been considered sequential steps in
      inflorescence development, factors that control the progression of floral
      meristem development may regulate the final outcome of UCM differentiation, and
      thus affect fruitfulness. A comparison of the expression profiles of the master
      regulators of floral meristem identity (FMI) during development of fruitful and
      non-fruitful buds along the same cane allowed associating the expression of a
      homolog of terminal flower 1 (TFL1, a negative regulator of FMI) to fruitful
      buds, and the expression of positive FMI regulators to non-fruitful buds.
      Combined with (a) cytokinin-induced upregulation of VvTFL1A expression in
      cultured tendrils, which accompanied cytokinin-derived tendril transformation
      into branched, inflorescence-like structures, (b) positive regulation of VvTFL1A
      expression by cytokinin, which was demonstrated in transgenic embryonic culture
      expressing GUS reporter under the control of VvTFL1A promoter, and (c) a
      significantly higher level of active cytokinins in fruitful positions, the data
      may support the assumption of cytokinin-regulated VvTFL1A activity's involvement
      in the control of inflorescence development. Such activity may delay acquisition
      of FMI and allow an extended branching period for the UCM, resulting in the
      differentiation of inflorescence primordia.

PMID- 21863251
TI  - Adenomatous tumors of the middle ear and temporal bone: clinical, morphological
      and tumor biological characteristics of challenging neoplastic lesions.
AB  - Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this
      retrospective study, we examined nine patients who underwent surgery for an
      adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven
      patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary
      tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic,
      immunohistochemical and DNA image cytometrical characteristics that can help to
      correctly classify these tumors. Therapy consisted of surgical excision of the
      tumors in eight cases. In one elderly patient, only a large biopsy was taken,
      because this patient suffered from cardial and kidney disorders and was not
      suitable for an extended surgical approach. This patient received stereotactic
      radiotherapy. Seven patients underwent planned second look operation. Recurrences
      occurred in three patients (one with APT, two with MEA), whereas in two of these
      cases rather a residual tumor due to initial incomplete tumor resection occurred.
      By image analysis, DNA cytometry MEA were considered benign, whereas the
      appearance of aneuploid tumor cells in APT confirmed these tumors as low grade
      malignant lesions. The proliferation rates were equally low in both entities. APT
      and MEA are tumor entities which can only be correctly classified by a synopsis
      of histopathology, immunohistochemistry and DNA image cytometry. The recommended
      therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau
      syndrome has to be excluded.

PMID- 21863252
TI  - Innate immunity in the pathogenesis of psoriasis.
AB  - Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1
      and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the
      release of inflammatory cytokines that promote further recruitment of immune
      cells, keratinocyte proliferation and sustained inflammation. The innate immune
      system is the first line of defence against infection and plays a crucial role in
      the initiation of the adaptive immune response. The presence of innate immune
      cells and their products in psoriatic skin plaques suggests a role for innate
      immunity in this disease. In addition, the innate immune system can direct the
      development of pathogenic Th cells in psoriasis. In this article, we will
      summarise the role of the innate immune system in psoriasis with particular
      emphasis on the role of cytokines, signalling pathways and cells of the innate
      immune system.

PMID- 21863253
TI  - Severe bleeding eyelid after trivial trauma: conjunctival metastasis of a renal
      cell carcinoma.

PMID- 21863254
TI  - Pain during second eye cataract surgery under topical anesthesia: an
      intraindividual study.
AB  - BACKGROUND: Aim of the study was to investigate: 1) if second eye cataract
      surgery under topical anesthesia is more painful than surgery on the first eye,
      2) if pain experienced during the procedure on the first eye may predict the pain
      of the second procedure, and 3) if patients' cooperation is different between the
      first and the second eye procedure. METHODS: Seventy-three consecutive patients
      undergoing bilateral non-simultaneous cataract surgery were prospectively
      included in the study. Surgical technique was sutureless clear corneal
      phacoemulsification under topical anesthesia. Immediately after surgery every
      patient graded the pain experienced using a visual analogue scale (VAS) from 0
      (no pain) to 10 (unbearable pain). At the end of each procedure the surgeon
      graded patients' cooperation using a 4-point scale. RESULTS: Mean VAS score was
      2.35 (SD 2.63) for the first eye and 2.89 (SD 2.93) for the second eye. Such a
      difference was not statistically significant (p = 0.1777, Wilcoxon test). The
      correlation between the VAS score of the first and that of the second procedure
      was statistically significant (r = 0.5514, p < 0.0001, Spearman rank
      correlation). Patients' cooperation was 2.64 (SD 0.63) during the first procedure
      and 2.52 (SD 0.79) during the second procedure; this difference was not
      statistically significant (p = 0.1769, Wilcoxon matched-pairs signed-ranks test).
      CONCLUSIONS: After uneventful cataract surgery under topical anesthesia, pain
      experienced and cooperation did not differ between first and second eye
      procedures. A correlation was found between pain scores of the first and the
      second eye procedures.

PMID- 21863255
TI  - Use of intravitreal bevacizumab injections to treat type 1 idiopathic macular
      telangiectasia.

PMID- 21863256
TI  - Ocular response analyzer to assess corneal biomechanical properties in
      exfoliation syndrome and exfoliative glaucoma.
AB  - BACKGROUND: The aim of this work was to investigate the differences in corneal
      biomechanical parameters between healthy and exfoliation syndrome (EXS) and
      exfoliative glaucoma (EXG) patients. METHODS: Two hundred and forty-four eyes of
      102 healthy, 64 EXS, and 78 EXG patients were included in the study. Corneal
      biomechanical parameters were measured using an ocular response analyzer (ORA).
      Central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The
      differences in ORA parameters between study and control group participants were
      analyzed using Student's t test. RESULTS: In healthy subjects, EXS and EXG eyes
      mean corneal hysteresis (CH) values were 9.4 +/- 1.4 mmHg, 8.5 +/- 1.5 mmHg and
      6.9 +/- 2.1 mmHg, respectively. The difference in mean CH between the EXG and the
      other two groups were statistically significant (p < 0.01 for both comparisons).
      CH was significantly lower in EXS patients than that of healthy eyes (p < 0.001).
      Mean corneal resistance factor (CRF) values were 9.8 +/- 1.6 mmHg, 9.3 +/- 1.8
      mmHg and 9.5 +/- 2.6 mmHg, respectively. Except for the difference between the
      control and EXS eyes (p = 0.004), no statistically significant difference was
      found between the groups in relation to mean CRF. There were no significant
      differences in CCT between the control eyes and exfoliative eyes with or without
      glaucoma. CONCLUSIONS: In this study, CH was found to be significantly lower in
      eyes with exfoliation. Further studies are needed to establish the relationships
      between exfoliation, ocular biomechanics, and glaucoma.

PMID- 21863257
TI  - BRCA1 R71K missense mutation contributes to cancer predisposition by increasing
      alternative transcript levels.
AB  - Mutation screening of the breast and ovarian cancer predisposition genes BRCA1
      and BRCA2 is becoming an increasingly important part of clinical practice.
      Classification of rare non-truncating sequence variants in the BRCA1 and BRCA2
      genes is problematic because it is not known whether these subtle changes alter
      function sufficiently to predispose cells to cancer development. The BRCA1 331G >
      A substitution mutation, which occurs at the last nucleotide of exon 5, results
      in an Arg-to-Lys change at codon 71 (R71K). cDNA analysis indicated that the R71K
      mutation significantly increases the level of a transcript, characterized by a 22
      bp deletion in exon 5, which putatively produces a truncated BRCA1 protein of 63
      amino acids. The mutation completely abolishes normal splicing as the mutant
      allele does not generate any normal transcript. Analysis of a tumor specimen
      indicates loss of heterozygosity. These results support the conclusion that BRCA1
      331G > A (R71K) is a deleterious mutation.

PMID- 21863258
TI  - Alteration of Y-box binding protein-1 expression modifies the response to
      endocrine therapy in estrogen receptor-positive breast cancer.
AB  - Y-box binding protein-1 (YB-1) plays an important role in tumor progression and
      drug resistance. This study examined whether YB-1 is involved in the alteration
      of response to endocrine therapy in estrogen receptor (ER)-positive breast cancer
      cells. MCF7 cells that stably expressed YB-1 (MCF7-YB-1) and vector control cells
      (MCF7-vector) were established. These cells were used to analyze the expression
      of the factors related to ER and growth factor receptor signaling pathways and
      responses to antiestrogens (tamoxifen and fulvestrant) and estrogen responsive
      element (ERE) activity. The effect of knocking down endogenous YB-1 expression
      was tested in wild-type MCF7 cells. In addition, the expression of YB-1 and the
      factors related to ER and growth factor receptor signaling pathways were
      evaluated in clinical breast cancers treated with preoperative chemotherapy. The
      expression of HER2, AIB1, p-Erk, and c-Myc was increased in MCF7-YB-1 cells. In
      contrast, knocking down of YB-1 decreased the expression of these factors but
      increased the expression of ERalpha in wild-type MCF7 cells. Furthermore,
      sensitivity to antiestrogens was decreased in the MCF7-YB-1 in comparison to that
      in MCF7-vector cells. The introduction of YB-1 into MCF7 cells inhibited
      apoptosis and cell cycle arrest at G1 phase induced by antiestrogens. In MCF7-YB
      1 cells, the expression levels of p-Erk and c-Myc were continuously upregulated
      when cells were treated with either tamoxifen or fulvestrant. The ERE activity
      was reduced in MCF7-YB-1 cells in comparison to MCF7-vector cells, and the ERE
      activity in MCF7-YB-1 cells was inhibited by fulvestrant at a lower concentration
      than that which inhibited the ERE activity in MCF7-vector cells. In ER-positive
      clinical breast cancers treated with preoperative chemotherapy, significantly
      more number of specimens that showed increased or positive YB-1 expression after
      chemotherapy was positive for HER2 expression. These data suggest that alteration
      of YB-1 may modify the crosstalk between the ER pathway and HER2 pathway in ER
      positive breast cancer cells, and consequently, may alter the response to
      endocrine therapy in ER-positive breast cancer cells.

PMID- 21863259
TI  - Mechanically induced experimental knee osteoarthritis benefits from anti
      inflammatory and immunomodulatory properties of simvastatin via inhibition of
      matrix metalloproteinase-3.
AB  - BACKGROUND: We investigated the anti-inflammatory and immunomodulatory effect of
      simvastatin on articular cartilage via the inhibition of matrix metalloproteinase
      3 (MMP-3), a matrix-degrading enzyme, in a mechanically induced experimental
      osteoarthritis (OA) animal model. MATERIALS AND METHODS: Twenty-seven albino
      Wistar rats were divided in three groups of equal number. Unphysiologic loading
      of articular cartilage was simulated by transecting anterior cruciate ligaments
      of the right knees of 18 rats consisting of groups 1 and 2. Nine animals in group
      2 received orally administered simvastatin 20 mg/kg per day by gavage for 8
      weeks. Animals in group 3 were sham operated. All animals were sacrificed at
      postoperative 8 weeks. Effects of simvastatin on disease progression was
      evaluated by documenting OA changes in cartilage specimens using Osteoarthritis
      Research Society International (OARSI) OA cartilage histopathology assessment
      system scores combined with the percentage of MMP-3 expression in chondrocytes.
      RESULTS: Simvastatin treatment significantly down-regulated the percentage of MMP
      3 expression in chondrocytes as assessed by immunohistochemistry methods.
      Suppression of this matrix-degrading enzyme by simvastatin also reduced OARSI
      scores, suggesting the potential for statins against OA progression. CONCLUSIONS:
      Following knee trauma, OA initiates at the molecular level in a short period of
      time. Irreversible structural changes in cartilage that require demanding
      treatment strategies led us to focus on effective measures to prevent OA. Statins
      have immunomodulatory and anti-inflammatory properties independent from their
      serum-cholesterol-lowering effects. One of these widely used drugs, simvastatin,
      showed beneficial effects on OA progression and extent by reducing cartilage
      degradation in our experimental setting. If these results are confirmed by human
      trials, simvastatin might be considered by orthopedic surgeons as a disease
      modifying drug during the early inflammatory phase of posttraumatic OA.

PMID- 21863260
TI  - Potentiation of spontaneous and evoked cortical electrical activity after
      spreading depression: in vivo analysis in well-nourished and malnourished rats.
AB  - Cortical spreading depression (CSD) is influenced by brain excitability and is
      related to neurological diseases, such as epilepsy. In vitro evidence indicates
      that neuronal electrical activity is potentiated after CSD. Malnutrition can
      cause electrophysiological changes in the brain, both in animals and in humans.
      Here, we investigated in vivo whether CSD potentiates the amplitude of
      electrocorticogram (ECoG) and of transcallosal evoked responses in adult well
      nourished (W), early-malnourished (M), and food-restricted rats. ECoG amplitudes
      were compared before and after CSD, at two parietal regions (designated the
      anterior and posterior regions). In the anterior region, post-CSD amplitudes of
      the ECoG waves were 13-23% higher (P < 0.05) than the pre-CSD values in all
      groups. In the posterior region, amplitudes increased 22% in the M group only (P
      < 0.05). In a fourth CSD-free group, ECoG amplitude did not change during the
      four recording hours. Transcallosal electrically evoked cortical responses also
      increased 21.5 +/- 9.6% and 41.8 +/- 28.5%, after CSD, in the W and M conditions,
      respectively, as compared to pre-CSD values. The data support the hypothesis of
      an in vivo CSD potentiation on cortical excitability as recorded by spontaneous
      and evoked electrical activity and modulation by nutritional status.

PMID- 21863261
TI  - Preserved grip selection planning in chronic unilateral upper extremity amputees.
AB  - Upper limb amputees receive no proprioceptive or visual sensory feedback about
      their absent hand. In this study, we asked whether chronic amputees nevertheless
      retain the ability to accurately plan gripping movements. Fourteen patients and
      matched controls performed two grip selection tasks: overt grip selection (OGS),
      in which they used their intact hand to grasp an object that appeared in
      different orientations using the most natural (under- or overhand) precision
      grip, and prospective grip selection (PGS), in which they selected the most
      natural grip for either hand without moving. We evaluated planning accuracy by
      comparing concordance between grip preferences expressed in PGS vs. OGS for the
      intact hand and PGS vs. the inverse of OGS responses for the affected hand.
      Overall, amputees showed no deficits in the accuracy of grip selection planning
      based on either hand and a consistent preference for less awkward hand postures.
      We found no evidence for a speed-accuracy tradeoff. Furthermore, selection
      accuracy did not depend on phantom mobility, phantom limb pain, time since
      amputation, or the residual limb's shoulder posture. Our findings demonstrate
      that unilateral upper limb amputees retain the ability to plan movements based on
      the biomechanics of their affected hand even many years after limb loss. This
      unimpaired representation may stem from persistent higher-level activity
      independent internal representations or may be sustained by sensory feedback from
      the intact hand.

PMID- 21863262
TI  - The effect of social context on the use of visual information.
AB  - Social context modulates action kinematics. Less is known about whether social
      context also affects the use of task relevant visual information. We tested this
      hypothesis by examining whether the instruction to play table tennis
      competitively or cooperatively affected the kind of visual cues necessary for
      successful table tennis performance. In two experiments, participants played
      table tennis in a dark room with only the ball, net, and table visible. Visual
      information about both players' actions was manipulated by means of self-glowing
      markers. We recorded the number of successful passes for each player
      individually. The results showed that participants' performance increased when
      their own body was rendered visible in both the cooperative and the competitive
      condition. However, social context modulated the importance of different sources
      of visual information about the other player. In the cooperative condition,
      seeing the other player's racket had the largest effects on performance increase,
      whereas in the competitive condition, seeing the other player's body resulted in
      the largest performance increase. These results suggest that social context
      selectively modulates the use of visual information about others' actions in
      social interactions.

PMID- 21863263
TI  - Comparison of octreotide LAR and lanreotide autogel as post-operative medical
      treatment in acromegaly.
AB  - Long-acting somatostatin analogs are frequently used as adjuvant treatment of
      acromegaly patients after noncurative surgery. This sudy aims to compare the
      efficacy of octreotide long-acting release (OCT) and lanreotide Autogel (LAN) in
      acromegaly patients. Sixty-eight patients not cured by transsphenoidal endoscopic
      or microscopic pituitary surgery between 2003 and 2009 were retrospectively
      analyzed (25 men; 43 women; mean age 41.1 +/- 10.9 years [range 18-65 years]).
      The patients were assigned randomly to OCT (n = 36) and LAN (n = 32) groups.
      Evaluations included insulin-like growth factor I (IGF-I) and growth hormone (GH)
      after oral glucose tolerance test (OGTT) 3, 6, 12 and 18 months after starting
      medical treatment; pituitary magnetic resonance imaging was performed before
      treatment and after 3 and 12 months. Patients achieving IGF-I levels within the
      age and gender normal range and GH level <1 MUg/l following OGTT were considered
      a 'biochemical cure'. Mean IGF-I and GH values and tumor volumes (cm(3)) in the
      LAN and OCT groups were similar in the post-operative period before initiation of
      medical treatment. A statistically significant decrease in GH and IGF-I levels
      was obtained for both treatment groups at each follow-up visit compared to the
      previous value. Tumor shrinkage after 12 months of treatment was statistically
      significant in both groups but the percentage tumor shrinkage (28.5% vs. 34.9%, P
      = 0.166) and rate of patients achieving biochemical cure (63.9 and 78.1%, P =
      0.454) were similar between OCT and LAN groups, respectively. OCT and LAN
      treatment options have similar efficacy for ensuring biochemical cure and tumor
      shrinkage in acromegaly patients who had noncurative surgery.

PMID- 21863265
TI  - Characterization of heavy metals in water and sediments in Taihu Lake, China.
AB  - To explore a comprehensive status of heavy metals in the Taihu Lake, which is one
      of the most important waters in China, water and sediment samples were taken
      throughout the lake during April to May of 2010, and metal elements (Cu, Cd, Cr,
      Ni, Pb, Sn, Sb, Zn, Mn) were analyzed in the water column, interstitial water and
      sediment. Relevant standards were used to assess the sediment and water quality.
      Results show that, in the lake water column, the average concentration of all
      metals ranged from 0.047 MUg/l (Cd) to 8.778 MUg/l (Zn). The concentration in the
      river water was usually higher than in the lake water for many metals. In the
      interstitial water Mn was significantly higher than that in water column, and
      other metals had no significant difference between the two media. In the surface
      sediment, average metal content ranged from 1.325 mg/kg (Cd) to 798.2 mg/kg (Mn).
      Spatially, contents of many metals were higher in Zhushan Bay than in other lake
      areas, and there existed a clear content gradient from the river to the lake for
      both water and sediment. On the sediment profiles, many metals presented an
      increasing trend from the depth of 15-20 cm to the top, which is indicative of
      the impact of increasingly intensive human activities from that period. Quality
      assessment indicates that metals in water phase are generally safe compared with
      USEPA "National Recommended Water Quality Criteria," with the exception of Mn in
      the interstitial water and Sb in the river water. Whereas the sediment is widely
      contaminated with metals to some extent compared with the "Consensus-Based
      Sediment Quality Guidelines," and Cu, Cr, and Ni are more likely to raise
      ecological risks. This work could be a basis for the ongoing China's criteria
      strategy.

PMID- 21863264
TI  - HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA
      algorithm in patients with gynaecological diseases.
AB  - The aim of this study is to evaluate a new tumour marker, HE4, in comparison with
      CA 125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in healthy women and
      in patients with benign and malignant gynaecological diseases. CA 125 and HE4
      serum levels were determined in 66 healthy women, 285 patients with benign
      gynaecological diseases (68 endometriosis, 56 myomas, 137 ovarian cysts and 24
      with other diseases), 33 patients with non-active gynaecological cancer and 143
      with active gynaecological cancer (111 ovarian cancers). CA 125 and HE4 cut-offs
      were 35 U/mL and 150 pmol/L, respectively. ROMA algorithm cut-off was 13.1 and
      27.7 for premenopausal or postmenopausal women, respectively. HE4, CA 125 and
      ROMA results were abnormal in 1.5%, 13.6% and 25.8% of healthy women and in 1.1%,
      30.2% and 12.3% of patients with benign diseases, respectively. Among patients
      with cancer, HE4 (in contrast to CA 125) had significantly higher concentrations
      in ovarian cancer than in other malignancies (p < 0.001). Tumour marker
      sensitivity in ovarian cancer was 79.3% for HE4, 82.9% for CA 125 and 90.1% for
      ROMA. Both tumour markers, HE4 and CA 125 were related to tumour stage and
      histological type, with the lowest concentrations in mucinous tumours. A
      significantly higher area under the ROC curve was obtained with ROMA and HE4 than
      with CA 125 in the differential diagnosis of benign gynaecological diseases
      versus malignant ovarian cancer (0.952, 0.936 and 0.853, respectively). Data from
      our population indicate that ROMA algorithm might be further improved if it is
      used only in patients with normal HE4 and abnormal CA 125 serum levels (cancer
      risk for this profile is 44.4%). ROMA algorithm in HE4 positive had a similar
      sensitivity and only increases the specificity by 3.2% compared to HE4 alone.

PMID- 21863266
TI  - Ambient ozone injury to forest plants in Northeast and North Central USA: 16
      years of biomonitoring.
AB  - The US Forest Service administers a long-term, nationwide ozone biomonitoring
      program in partnership with other state and federal agencies to address national
      concerns about ozone impacts on forest health. Biomonitoring surveys begun in
      1994 in the East and 1998 in the West provide important regional information on
      ozone air quality and a field-based record of ozone injury unavailable from any
      other data source. Surveys in the Northeast and North Central subregions cover
      450 field sites in 24 states where ozone-sensitive plants are evaluated for ozone
      induced foliar injury every year. Sites are typically large, undisturbed openings
      (>3 acres in size) close to forested areas where >3 bioindicator species are
      available for evaluation. Over the 16-year sampling period, injury indices have
      fluctuated annually in response to seasonal ozone concentrations and site
      moisture conditions. Sites with and without injury occur at all ozone exposures
      but when ambient concentrations are relatively low, the percentage of uninjured
      sites is much greater than the percentage of injured sites; and regardless of
      ozone exposure, when drought conditions prevail, the percentage of uninjured
      sites is much greater than the percentage of injured sites. Results indicate a
      declining trend in foliar injury especially after 2002 when peak ozone
      concentrations declined across the entire region.

PMID- 21863267
TI  - Deep brain stimulation of the globus pallidus internal improves symptoms of
      chorea-acanthocytosis.
AB  - Chorea-acanthocytosis is a rare autosomal recessive disorder. To date, treatment
      is only symptomatic and supportive. Results from the few reports of chorea
      acanthocytosis patients treated with deep brain stimulation (DBS) have been
      inconsistent. We present case reports for two patients with chorea-acanthocytosis
      who received DBS treatment and compare the outcomes with results from the
      literature. Both patients showed the typical clinical features of chorea
      acanthocytosis with motor symptoms resistant to medical treatment. Chorea was
      significantly improved following low-frequency DBS treatment in both patients.
      However, dystonia was only mildly improved. Four chorea-acanthocytosis patients
      treated with DBS treatment have been reported in the literature. One patient had
      improvement with low-frequency DBS stimulation, while another two had improvement
      with higher-frequency DBS. One patient, however, did not improve with either low
      frequency or high-frequency DBS. Bilateral DBS to the GPi can improve chorea and
      dystonia in some patients with intractable chorea-acanthocytosis. However,
      selection criteria for the most promising candidates must be defined, and the
      long-term benefits evaluated in clinical studies.

PMID- 21863268
TI  - Hypertrophic cervical spinal cord pachymeningitis due to Treponema pallidum
      infection.
AB  - Neurosyphilis is recognized as a potential cause of hypertrophic pachymeningitis,
      but modern reports are few. A middle-aged man presented to hospital with a 1
      month history of lower limb pain and weakness. Cerebrospinal fluid analysis
      showed pleocytosis with high protein levels and a positive venereal disease
      research laboratory result. Cervical spinal cord resonance imaging disclosed a
      dural contrast enhancement suggestive of pachymeningitis. Biopsy of the dura
      mater revealed a thick inflammatory process. Despite being treated accordingly,
      the patient rapidly deteriorated and died. The patient was diagnosed as having
      subacute hypertrophic cervical pachymeningitis which caused spinal cord
      compression. Serological evidence of neurosyphilis was present. Physicians should
      still be aware of this cause of hypertrophic pachymeningitis.

PMID- 21863269
TI  - Effects of statin and deferoxamine administration on neurological outcomes in a
      rat model of intracerebral hemorrhage.
AB  - Deferoxamine (DFX), a potent iron-chelating agent, reduces brain edema and
      neuronal cell injury that develop due to the hemolysis cascade. Statins have
      neuroprotective effects via anti-inflammatory action and increment of cerebral
      blood flow after intracerebral hemorrhage (ICH). The purpose of this study was to
      identify the effects of combined DFX and statins treatment in an experimental ICH
      rat model. The treatments were: intraperitoneal (i.p.) injection of DFX (group
      I), combined treatment of i.p. DFX and oral statins (group II), statins only
      (group III) and treatment with vehicle (group IV). Induction of ICH was performed
      with injection of bacterial collagenase type IV into the left striatum. After
      removal of the brain, hematoma volume, water content and brain atrophy were
      measured. Immunohistochemistry in the perihematomal region was performed for
      identification of microglial infiltration, astrocyte expression and apoptotic
      cell presence. Statistical analysis was performed using the non-parametric
      Kruskal-Wallis test and significance was evaluated when the p value was less than
      0.05. According to behavioral tests, significant differences among treatment
      groups were noted 4 weeks after ICH induction (p < 0.05). However, there were no
      significant differences among treatment groups in hematoma volume, brain water
      content or brain atrophy. In the perihematomal area, the activated microglial
      cells were reduced in the combined treatment group. Among the four groups, a
      significant difference in immunohistochemical staining was identified (p < 0.05).
      These results suggest that combined treatment with DFX and statins improves
      neurologic outcomes after ICH through reduction of microglial infiltration,
      apoptosis, inflammation and brain edema.

PMID- 21863270
TI  - A case of rheumatoid meningitis: pathologic and magnetic resonance imaging
      findings.
AB  - Central nervous system (CNS) involvement is extremely rare in patients with
      rheumatoid arthritis (RA). Additionally, most patients with CNS involvement have
      chronic and severe RA. We present a report of a 66-year-old man who was diagnosed
      with rheumatoid meningitis and CNS vasculitis without a history of RA. His
      initial symptom was seizure. Brain magnetic resonance imaging showed
      leptomeningeal enhancement.CSF analysis revealed slight increase in the number of
      white blood cells. An examination of viral markers and culture studies for
      infectious etiology were unremarkable. However, the rheumatoid factor was
      positive and the levels of anti-cyclic citrullinated peptide antibody were very
      high. The patient was diagnosed with rheumatoid meningitis and received steroid
      therapy. However, he developed CNS vasculitis. We suggested that the possibility
      of rheumatoid meningitis should be considered during the differential diagnosis
      stage in patients with uncontrolled meningitis, even though RA does not typically
      show CNS involvement.

PMID- 21863271
TI  - Fulminant multiple sclerosis (MS).
AB  - Fulminant multiple sclerosis (MS) is the most malignant form of MS which usually
      leads to death in few weeks. Although it can be accompanied by optic neuritis
      (ON), but long interval between ON and the grave onset has not been reported.
      Fulminant MS usually occurs as the first onset and previous ON is not common. We
      report a rare case of 30-year-old woman with a history of ON 1 year ago. The
      rapid deterioration to vegetative state followed by a seizure and previous ON
      differentiated this case from previous reported cases. The differential diagnosis
      of a rapidly progressive leucoencephalopathy in this patient includes
      inflammatory, vascular, infectious and toxic disorders. Regarding the previous
      history of optic neuritis with positive brain MRI (multiple T2 hyperintense
      lesions in white matter) in our patient, multiple sclerosis is the most probable
      diagnosis. More effective treatments, such as plasmapheresis and
      cyclophosphamide, that influenced on the prognosis of some previous patients
      could be useful, but should be performed before progressive brain atrophy
      emerges.

PMID- 21863272
TI  - Microsurgical and tractographic anatomical study of insular and transsylvian
      transinsular approach.
AB  - This study is to define the operative anatomy of the insula with emphasis on the
      transsylvian transinsular approach. The anatomy was studied in 15 brain
      specimens, among five were dissected by use of fiber dissection technique;
      diffusion tensor imaging of 10 healthy volunteers was obtained with a 1.5-T MR
      system. The temporal stem consists mainly of the uncinate fasciculus, inferior
      occipitofrontal fasciculus, Meyer's loop of the optic radiation and anterior
      commissure. The transinsular approach requires an incision of the inferior
      limiting sulcus. In this procedure, the fibers of the temporal stem can be
      interrupted to various degrees. The fiber dissection technique is a very relevant
      and reliable method for neurosurgeons to study the details of brain anatomic
      features. The DTI fiber tracking technique can identify the fiber tracts of the
      temporal stem. Moreover, it will also help further functional study of human
      insula.

PMID- 21863273
TI  - Variable phenotypes in a family with mitochondrial encephalomyopathy harboring a
      3291T > C mutation in mitochondrial DNA.
AB  - We present a Japanese family suffering from mitochondrial encephalomyopathy
      associated with a T-to-C transition at mitochondrial DNA (mtDNA) nucleotide
      position 3291. Clinical manifestations of the patients include cerebellar ataxia
      with myopathy, recurrent headache, and myoclonus and epilepsy. The phenotypic
      variation among the affected members of a single family and the mutational
      analysis showing maternal inheritance in a heteroplasmic fashion are consistent
      with well-recognized phenomena associated with many pathogenic point mutations of
      mtDNA tRNA genes. The 3291 mutation is a rare mtDNA mutation whose clinical
      presentation had only been reported in three sporadic cases. This is the first
      report of a family segregating the 3291 mutation with multigenerational
      matrilinear recurrence of mitochondrial encephalopathy. Our findings provide
      conclusive evidence for the pathogenicity of the 3291T > C mutation in mtDNA and
      its characteristic clinical heterogeneity.

PMID- 21863274
TI  - Evaluation of routinely performed hematological and biochemical parameters for
      the prognosis of acute ischemic stroke patients.
AB  - We have investigated serial changes in routine hematological and biochemical
      analysis in the follow-up samples collected from acute ischemic stroke (AIS)
      patients (n = 17) at admission (0 h) and 24, 48, 72 and 144 h after admission,
      respectively, to determine their prognostic significance. Blood samples from age
      and sex matched healthy control subjects (n = 12) were also collected. We
      observed significant changes in erythrocyte sedimentation rate (ESR), white blood
      cell count (WBC), polymorph, lymphocyte, and total protein levels in discharged
      and expired AIS patients. These changes were more in expired AIS patient
      throughout the follow-up. Similarly low hemoglobin (Hb) and globulin were
      observed only in expired AIS patient. Thus ESR, WBC, polymorph, lymphocyte, and
      total protein may be used as a predictor for severity of AIS. Similarly low Hb
      and globulin in AIS patient may be used as a predictive biomarker for short-term
      mortality after AIS.

PMID- 21863277
TI  - 3-Hydroxyisobutyrate aciduria and mutations in the ALDH6A1 gene coding for
      methylmalonate semialdehyde dehydrogenase.
AB  - 3-hydroxyisobutyric aciduria is an organic aciduria with a poorly understood
      biochemical basis. It has previously been assumed that deficiency of 3
      hydroxyisobutyrate dehydrogenase (HIBADH) in the valine catabolic pathway is the
      underlying enzyme defect, but more recent evidence makes it likely that
      individuals with 3-hydroxyisobutyryic aciduria represent a heterogeneous group
      with different underlying mechanisms, including respiratory chain defects or
      deficiency of methylmalonate semialdehyde dehydrogenase. However, to date
      methylmalonate semialdehyde dehydrogenase deficiency has only been demonstrated
      at the gene level for a single individual. We present two unrelated patients who
      presented with developmental delay and increased urinary concentrations of 3
      hydroxyisobutyric acid. Both children were products of consanguineous unions and
      were of European or Pakistani descent. One patient developed a febrile illness
      and subsequently died from a hepatoencephalopathy at 2 years of age. Further
      studies were initiated and included tests of the HIBADH enzyme in fibroblast
      homogenates, which yielded normal activities. Sequencing of the ALDH6A1 gene
      (encoding methylmalonate semialdehyde dehydrogenase) suggested homozygosity for
      the missense mutation c.785 C > A (S262Y) in exon 7 which was not found in 210
      control alleles. Mutation analysis of the ALDH6A1 gene of the second patient
      confirmed the presence of a different missense mutation, c.184 C > T (P62S),
      which was also identified in 1/530 control chromosomes. Both mutations affect
      highly evolutionarily conserved amino acids of the methylmalonate semialdehyde
      dehydrogenase protein. Mutation analysis in the ALDH6A1 gene can reveal a cause
      of 3-hydroxyisobutyric aciduria, which may present with only slightly increased
      urinary levels of 3-hydroxyisobutyric acid, if a patient is metabolically stable.

PMID- 21863278
TI  - Clinical practice and the development of evidence.

PMID- 21863279
TI  - Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b
      patients.
AB  - Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6
      phosphate transporter and is characterized by impaired glucose homeostasis. In
      addition, GSD-1b is associated with chronic neutropenia resulting in recurrent
      infections and inflammatory bowel disease. It is unclear whether the neutropenia
      is solely due to enhanced apoptosis of mature neutrophils or whether aberrant
      neutrophil development may also contribute. Here we demonstrate that
      hematopoietic progenitors from GSD-1b patients are not impaired in their capacity
      to develop into mature neutrophils. However, optimal survival of neutrophil
      progenitors from GSD-1b patients requires high glucose levels (> 200 mg dl(-1)),
      suggesting that even under normoglycemic conditions these cells are more prone to
      apoptosis. Furthermore, analysis of cytokine levels in peripheral blood suggests
      an inflammatory state with an inverse correlation between the level of
      inflammation and the number of neutrophils. Finally, in some patients, with low
      numbers of peripheral blood neutrophils, high numbers of neutrophils were
      observed in the intestine. Together, these results suggest that the neutropenia
      observed in GSD-1b patients is not caused by impaired maturation, but may be
      caused by both increased levels of apoptosis and egress of neutrophils from the
      blood to the inflamed tissues.

PMID- 21863281
TI  - Psychiatric patients' views on why their involuntary hospitalisation was right or
      wrong: a qualitative study.
AB  - PURPOSE: To explore involuntary patients' retrospective views on why their
      hospitalisation was right or wrong. METHODS: Involuntary patients were recruited
      from 22 hospitals in England and interviewed in-depth. The study drew on grounded
      theory and thematic analysis. RESULTS: Most of the patients felt mentally unwell
      before admission and out of control during their treatment. Despite these common
      experiences, three groups of patients with distinct views on their involuntary
      hospitalisation were identified: those who believed that it was right, those who
      thought it was wrong and those with ambivalent views. Those with retrospectively
      positive views believed that hospitalisation ensured that they received
      treatment, averted further harm and offered them the opportunity to recover in a
      safe place. They felt that coercion was necessary, as they could not recognise
      that they needed help when acutely unwell. Those who believed that involuntary
      admission was wrong thought that their problems could have been managed through
      less coercive interventions, and experienced hospitalisation as an unjust
      infringement of their autonomy, posing a permanent threat to their independence.
      Patients with ambivalent views believed that they needed acute treatment and that
      hospitalisation averted further harm. Nonetheless, they thought that their
      problems might have been managed through less coercive community interventions or
      a shorter voluntary hospitalisation. CONCLUSIONS: The study illustrates why some
      patients view their involuntary hospitalisation positively, whereas others
      believe it was wrong. This knowledge could inform the development of
      interventions to improve patients' views and treatment experiences.

PMID- 21863282
TI  - The association of African Americans' perceptions of neighborhood crime and drugs
      with mental illness.
AB  - BACKGROUND: Many African Americans are socioeconomically disadvantaged and live
      in neighborhoods containing chronic sources of stress. Although environmental
      stressors can contribute to the development of mental illness, there is a paucity
      of national studies examining the association of neighborhood crime and drug
      problems with psychiatric disorders. This study aims to determine if higher
      levels of perceived neighborhood problems are associated with greater prevalence
      of 12-month and lifetime psychiatric disorders among African Americans. METHODS:
      To do so, we used cross-sectional data from the National Survey of American Life,
      which interviewed a nationally representative sample of 3,570 African Americans.
      RESULTS: Of these African Americans, nearly 20 and 40% reported that crime and
      drug use are problems in their neighborhoods, respectively. Respondents reporting
      high levels of perceived neighborhood crime or drug problems are 1.5-2.9 times
      more likely to have a 12-month psychiatric disorder and 1.4-2.1 times more likely
      to have a lifetime psychiatric disorder compared to the other respondents. After
      accounting for sociodemographics and chronic disease, neighborhood crime remains
      associated with 12-month mood, 12-month substance use, and lifetime substance use
      disorders, whereas neighborhood drug problems remain significantly associated
      with 12-month and lifetime anxiety and substance use disorders. CONCLUSIONS:
      Among African Americans perceived neighborhood problems are widespread and
      positively associated with psychiatric disorders. Consideration of neighborhood
      context is important to more comprehensively understand mental illness and its
      treatment in this population.

PMID- 21863283
TI  - The association between depression and parental ethnic affiliation and
      socioeconomic status: a 27-year longitudinal US community study.
AB  - PURPOSE: This study examined the extent to which parental SES and ethnic
      affiliation during adolescence are associated with Center for Epidemiologic
      Studies Depression Scale (CES-D) scores compatible with depression during
      adulthood. METHODS: The data were extracted from the US National Longitudinal
      Survey of Youth (NLSY79) conducted in 1979 on several ethnic groups (African
      Americans, Hispanics and Others). These data included paternal socio-economic
      status (SES) when respondents (N = 8,331) were on average aged 18. The CES-D was
      re-administered 27 years later to assess the presence of depression. RESULTS:
      Adjusted for age, binary logistic regression modeling showed that parental low
      SES increased the risk of CES-D of scores compatible with depression across
      ethnic groups for both genders. A gradient was observed of an increased
      likelihood of depression scores with lower parental SES levels: among African
      American respondents, depression scores were highest at the lowest parental SES
      levels (OR = 3.25, 95% CI 2.19-4.84) and the risk dropped at medium (OR = 3.00,
      95% CI 1.96-4.59), and highest SES levels (OR = 1.85, 95% CI 1.12-3.07). An
      analogous pattern was generally found for each ethnic group. CONCLUSIONS: Low
      parental SES during adolescence significantly increases the likelihood of CES-D
      scores compatible with depression during adulthood across US ethnic groups and in
      both genders.

PMID- 21863284
TI  - Analysis of differentially expressed proteins in colorectal cancer using
      hydroxyapatite column and SDS-PAGE.
AB  - Limitation on two dimensional (2D) gel electrophoresis technique causes some
      proteins to be under presented, especially the extreme acidic, basic, or membrane
      proteins. To overcome the limitation of 2D electrophoresis, an analysis method
      was developed for identification of differentially expressed proteins in normal
      and cancerous colonic tissues using self-pack hydroxyapatite (HA) column. Normal
      and cancerous colon tissues were homogenized and proteins were extracted using
      sodium phosphate buffer at pH 6.8. Protein concentration was determined and the
      proteins were loaded unto the HA column. HA column reduced the complexity of
      proteins mixture by fractionating the proteins according to their ionic strength.
      Further protein separation was accomplished by a simple and cost effective sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis method. The protein bands were
      subjected to in-gel digestion and protein analysis was performed using
      electrospray ionization (ESI) ion trap mass spectrometer. There were 17
      upregulated proteins and seven downregulated proteins detected with significant
      differential expression. Some of these proteins were low abundant proteins or
      proteins with extreme pH that were usually under presented in 2D gel analysis. We
      have identified brain mitochondrial carrier protein 1, T-cell surface
      glycoprotein CD1a, SOSS complex subunit B2, and Protein Jade 1 which were
      previously not detected in 2D gel analysis method.

PMID- 21863285
TI  - Activation of the unfolded protein response in primary acute myeloid leukemia
      cells.

PMID- 21863287
TI  - RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and
      tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal
      translocations.
AB  - Recently, RCSD1 was identified as a novel gene fusion partner of the ABL1 gene.
      The RCSD1 gene, located at 1q23, is involved in t(1;9)(q23;q34) translocation in
      acute B lymphoblastic leukemia. Here we describe RCSD1-ABL1-positive B-cell acute
      lymphoblastic leukemia (ALL) followed by rapid clonal evolution exhibiting three
      rare reciprocal translocations. We performed breakpoint analysis of the
      transcript expressed by the RCSD1-ABL1 fusion gene. RT-PCR and sequence analyses
      detected transcription of a single RCSD1-ABL1 fusion gene variant, which had
      breakpoints in exon 3 of RCSD1 and exon 4 of ABL1. The RCSD1 portion of the RCSD1
      ABL1 fusion transcript consists of exons 1, 2, and 3. Tyrosine kinase inhibitors,
      imatinib and dasatinib, coadministered with dexamethasone achieved transient
      clinical effects in the present RCSD1-ABL1-positive ALL. However, leukemic cells
      rapidly became refractory to this treatment following the subsequent development
      of three additional reciprocal chromosomal translocations, t(5;16)(q33;q24),
      dic(18;20)(p11.2;q11.2) and t(10;19)(q24;p13.3). The present RCSD1-ABL1-positive
      ALL may represent a state of high chromosomal instability.

PMID- 21863286
TI  - Hematopoietic stem cell transplantation with reduced intensity conditioning from
      a family haploidentical donor in an infant with familial hemophagocytic
      lymphohistocytosis.
AB  - Allogeneic hematopoietic stem cell transplantation is the only curative method
      for patients with familial hemophagocytic lymphohistiocytosis (FHL). We present a
      case of a 3-month-old girl with Munc13-4 mutation (FHL3), who underwent bone
      marrow transplantation (BMT) from her human leukocyte antigen-haploidentical
      mother following reduced intensity conditioning (RIC) with fludarabine,
      melphalan, and busulfan. Engraftment after BMT was generally uneventful, with
      only mild acute graft versus host disease. Munc13-4 protein was restored
      following BMT, and she is well and free of disease 14 months after BMT. These
      results suggest that BMT with RIC from a family haploidentical donor may
      sufficiently restore immune regulation in infants, while lessening treatment
      related mortality and long-term sequelae.

PMID- 21863288
TI  - MRI of displaced meniscal fragments.
AB  - A torn meniscus frequently requires surgical fixation or debridement as
      definitive treatment. Meniscal tears with associated fragment displacement, such
      as bucket handle and flap tears, can be difficult to recognize and accurately
      describe on MRI, and displaced fragments can be challenging to identify at
      surgery. A displaced meniscal fragment can be obscured by synovium or be in a
      location not usually evaluated at arthroscopy. We present a pictorial essay of
      meniscal tears with displaced fragments in patients referred to a pediatric
      hospital in order to increase recognition and accurate interpretation by the
      radiologist, who in turn can help assist the surgeon in planning appropriate
      therapy.

PMID- 21863289
TI  - The importance of conventional radiography in the mutational analysis of skeletal
      dysplasias (the TRPV4 mutational family).
AB  - The spondylo and spondylometaphyseal dysplasias (SMDs) are characterized by
      vertebral changes and metaphyseal abnormalities of the tubular bones, which
      produce a phenotypic spectrum of disorders from the mild autosomal-dominant
      brachyolmia to SMD Kozlowski to autosomal-dominant metatropic dysplasia.
      Investigations have recently drawn on the similar radiographic features of those
      conditions to define a new family of skeletal dysplasias caused by mutations in
      the transient receptor potential cation channel vanilloid 4 (TRPV4). This review
      demonstrates the significance of radiography in the discovery of a new bone
      dysplasia family due to mutations in a single gene.

PMID- 21863290
TI  - Pulmonary vein flow pattern in children with bidirectional cavopulmonary
      connection or Fontan circuit.
AB  - BACKGROUND: Typical flow velocity profiles in the extraparenchymal pulmonary
      veins (PVs) demonstrate two major antegrade flow waves: a biphasic systolic wave
      (S), with S1 and S2 peaks and a monophasic early diastolic wave (D). Flow
      reversal during atrial systole (A) is common. There is agreement that the forward
      diastolic PV flow wave is caused by left ventricular relaxation with opening of
      the mitral valve. The origin of the PV systolic wave, however, remains a topic of
      debate. Some studies have suggested that the S wave is created by the relaxation
      of the left atrium and descent of the mitral valve plane. These studies have
      concluded that forces generated by the right ventricle (RV) have no effect on the
      S wave. Others suggest that the forward propagation of the right ventricular
      systolic pressure pulse is the major contributor to the S wave. OBJECTIVE: To
      determine whether any part of the systolic wave of PV flow is dependent on forces
      created by the right ventricle. MATERIALS AND METHODS: We assessed PV flow
      pattern, as obtained by cardiac MRI in 12 cases (39 pulmonary veins) with RV
      independent pulmonary circulation (bidirectional cavopulmonary connection or
      Fontan circulation). Phase-contrast imaging of the PVs was performed on a 1.5-T
      MR scanner with velocity encoding set at 120 cm/s. We compared these flow
      patterns with those of a control group of ten children (15 pulmonary veins) who
      had RV-dependent pulmonary circulation and underwent CMR for other indications.
      RESULTS: In all PVs of children with RV-independent pulmonary circulation the
      flow curves showed a single systolic peak in early systole (S1) with the S2 peak
      consistently absent. PV flow pattern in the control group consistently showed
      distinct early and late systolic peaks. CONCLUSION: This study supports the
      concept that S2 is caused by forward propagation of the right ventricular
      systolic pressure pulse. It also demonstrates that the S1 is independent of the
      right ventricle.

PMID- 21863291
TI  - Extracardiac complications of the Fontan circuit.
AB  - The Fontan operation is the primary surgical procedure used in the palliation of
      patients with univentricular cardiac physiology. With improved survival of
      children with congenital heart disease, long-term complications of the Fontan
      circuit are being encountered more frequently. Radiologists are more likely to
      see both the cardiac and extracardiac complications of the Fontan circuit.
      Awareness of the common extracardiac complications in children with failing
      Fontan circuits will aid the radiologist in making the appropriate diagnosis and
      guide the cardiologist caring for these patients.

PMID- 21863292
TI  - US-guided percutaneous needle biopsy of anterior mediastinal masses in children.
AB  - BACKGROUND: Anterior mediastinal masses in children are clinically challenging,
      requiring prompt histological diagnosis. OBJECTIVE: The purpose of this study was
      to review the experience with US-guided percutaneous core needle biopsy (PCNB) of
      anterior mediastinal masses in children, particularly with respect to safety and
      diagnostic accuracy. MATERIALS AND METHODS: We retrospectively reviewed the
      clinical presentation, imaging, sedation approach, procedural details and
      pathology results of US-guided PCNB of mediastinal masses that occurred during an
      8-year period (2001-2008). Complications were graded and pathology was
      categorized into four groups based on adequacy and diagnostic yield. RESULTS: 32
      US-guided PCNBs were performed on 32 children, mean age 12 years (range 18 months
      to 17 years), mean weight 48 kg (range 11.5 to 109 kg, median 49 kg). A coaxial
      US-guided technique was used, with a mean of 8.2 passes and a mean 7.6 cores
      obtained (range 2-15). There were no major complications. The biopsies were
      adequate in volume and quality of specimens in 29/32, and 25/32 were diagnostic.
      PCNB was diagnostic in all cases of non-Hodgkin disease. CONCLUSIONS: Experience
      with anterior mediastinal masses suggests that US-guided PCNB can be considered a
      viable, safe and accurate method of reaching a diagnosis in the pediatric
      population.

PMID- 21863293
TI  - Diphenyl ditelluride induces hypophosphorylation of intermediate filaments
      through modulation of DARPP-32-dependent pathways in cerebral cortex of young
      rats.
AB  - We studied the effect of different concentrations of diphenyl ditelluride
      (PhTe)(2) on the in vitro phosphorylation of glial fibrillary acidic protein
      (GFAP) and neurofilament (NF) subunits from cerebral cortex and hippocampus of
      rats during development. (PhTe)(2)-induced hypophosphorylation of GFAP and NF
      subunits only in cerebral cortex of 9- and 15-day-old animals but not in
      hippocampus. Hypophosphorylation was dependent on ionotropic glutamate receptors,
      as demonstrated by the specific inhibitors 10 MUM DL-AP5 and 50 MUM MK801, 100
      MUM CNQX and 100 MUM DNQX. Also, 10 MUM verapamil and 10 MUM nifedipine, two L
      voltage-dependent Ca(2+) channels (L-VDCC) blockers; 50 MUM dantrolene, a
      ryanodine channel blocker, and the intracellular Ca(2+) chelator Bapta-AM (50
      MUM) totally prevented this effect. Results obtained with 0.2 MUM calyculin A
      (PP1 and PP2A inhibitor), 1 MUM Fostriecin a potent protein phosphatase 2A (PP2A)
      inhibitor, 100 MUM FK-506 or 100 MUM cyclosporine A, specific protein phosphatase
      2B inhibitors, pointed to PP1 as the protein phosphatase directly involved in the
      hypophosphorylating effect of (PhTe)(2). Finally, we examined the activity of
      DARPP-32, an important endogenous Ca(2+)-mediated inhibitor of PP1 activity.
      Western blot assay using anti-DARPP-32, anti-pThr34DARPP-32, and anti-pThr75DARPP
      32 antibodies showed a decreased phosphorylation level of the inhibitor at Thr34,
      compatible with inactivation of protein kinase A (PKA) by pThr75 DARPP-32.
      Decreased cAMP and catalytic subunit of PKA support that (PhTe)(2) acted on
      neuron and astrocyte cytoskeletal proteins through PKA-mediated inactivation of
      DARPP-32, promoting PP1 release and hypophosphorylation of IF proteins of those
      neural cells. Moreover, in the presence of Bapta, the level of the PKA catalytic
      subunit was not decreased by (PhTe)(2), suggesting that intracellular Ca(2+)
      levels could be upstream the signaling pathway elicited by this neurotoxicant and
      targeting the cytoskeleton.

PMID- 21863294
TI  - Cigarette smoking, proteinuria, and renal function in middle-aged Japanese men
      from an occupational population.
AB  - OBJECTIVES: To clarify the renal effects of cigarette smoking in a middle-aged
      occupational population because the effects have previously been demonstrated
      mainly in community populations that included many elderly people who are thought
      to be vulnerable to such effects. METHODS: In 990 middle-aged men recruited from
      a chemical plant, proteinuria was measured by a dipstick method and the
      glomerular filtration rate was estimated (eGFR) using a formula proposed by the
      Japanese Society of Nephrology. RESULTS: Proteinuria was found in 4.6% of the
      current smokers and 1.5% of the never-smokers. It was found in 4.8% of the
      subjects having a Brinkman index (BI) of 400-599 and 6.3% of those having a BI of
      600 or above. The odds ratio for proteinuria in them was 2.94 (CI: 1.01-8.55) and
      3.61 (CI: 1.29-10.1), respectively, adjusting for possible confounders. The mean
      eGFR was higher in smokers than in nonsmokers throughout middle age up to 64
      years. Normal but high eGFR was found in 6.7% of the current heavy smokers and
      subnormal eGFR in 5.7% of the largest cumulative cigarette consumers in contrast
      to 3.0% or less of the never-smokers. Proteinuria was found in 13.3% of the
      subjects showing subnormal eGFR, specifically in 16.7% of the smokers and 8.3% of
      the nonsmokers. CONCLUSIONS: Smoking causes proteinuria in working middle-aged
      men. Smokers tend to have a high eGFR, but those with subnormal eGFR showed
      proteinuria most frequently. Whether the high eGFR in smokers will eventually
      decrease and cause proteinuria remains an important focus for further studies.

PMID- 21863295
TI  - Posterior cranial vault expansion performed with rapid distraction and time
      reduced consolidation in infants with syndromic craniosynostosis.

PMID- 21863296
TI  - Comparison of the metabolic energy cost of overground and treadmill walking in
      older adults.
AB  - We assessed whether the metabolic energy cost of walking was higher when measured
      overground or on a treadmill in a population of healthy older adults. We also
      assessed the association between the two testing modes. Participants (n = 20, 14
      men and 6 women aged between 65 and 83 years of age) were randomly divided into
      two groups. Half of them went through the overground-treadmill sequence while the
      other half did the opposite order. A familiarization visit was held for each
      participant prior to the actual testing. For both modes of testing, five walking
      speeds were experimented (0.67, 0.89, 1.11, 1.33 and 1.67 m s(-1)). Oxygen uptake
      was monitored for all walking speeds. We found a significant difference between
      treadmill and track metabolic energy cost of walking, whatever the walking speed.
      The results show that walking on the treadmill requires more metabolic energy
      than walking overground for all experimental speeds (P < 0.05). The association
      between both measures was low to moderate (0.17 < ICC < 0.65), and the standard
      error of measurement represented 6.9-15.7% of the average value. These data
      indicate that metabolic energy cost of walking results from a treadmill test does
      not necessarily apply in daily overground activities. Interventions aiming at
      reducing the metabolic energy cost of walking should be assessed with the same
      mode as it was proposed during the intervention. If the treadmill mode is
      necessary for any purposes, functional overground walking tests should be
      implemented to obtain a more complete and specific evaluation.

PMID- 21863297
TI  - Insulin therapy in diabetes and cancer risk: current understanding and
      implications for future study: proceedings from a meeting of a European Insulin
      Safety Consensus Panel, convened and sponsored by Novo Nordisk, held Tuesday
      October 5, 2010 at The Radisson Edwardian Heathrow Hotel, Hayes, Middlesex, UK.
AB  - INTRODUCTION: Interest in the possibility of certain insulin treatments having
      the potential to modify cancer development and prognosis was reawakened in 2009,
      following publication of several epidemiological studies addressing this issue.
      This interest extends to how diabetes itself and cancer might be linked, and
      makes desirable an exchange of expert views and knowledge to enhance
      understanding in this subject among those treating diabetes and cancer, or those
      developing diabetes therapies. METHODS: A European meeting was convened with
      participants invited based on known relevant interests in endocrinology,
      oncology, epidemiology, and insulin analog design and investigation. Experts in
      these fields were invited to present on relevant topics, with open discussions
      held after each presentation. RESULTS: Concern over the potential mitogenic
      properties of certain insulin analogs has arisen from some (but not all)
      epidemiological studies, although confounding factors render interpretation
      controversial. Future epidemiological studies are likely to strengthen confidence
      in drawing conclusions. Meanwhile, pharmacological studies, and a consideration
      of cancer pathophysiology, implicate increased insulin-like growth factor-1
      receptor affinity, and/or deranged insulin receptor interaction/signaling
      properties as possible a priori causes for concern with some insulin analogs.
      Again, interpretation of the body of pharmacological evidence is confounded by
      the array of test systems and methodologies used, and by studies frequently
      succumbing to methodological pitfalls. Reassuringly, most available insulin
      analogs do not differ in their receptor interaction response profile to human
      insulin, and for those that do there are reasons to question any potential
      clinical relevance. Nevertheless, it is desirable that new experimental models
      are devised that can better determine the likely clinical consequences of any
      variance in receptor response profile versus human insulin. CONCLUSION: More data
      are required to increase our understanding of this issue. To facilitate and
      disseminate such understanding, close cooperation and communication between
      diabetologists, epidemiologists, oncologists, and insulin engineers will be
      essential.

PMID- 21863298
TI  - Staged correction of an equinovarus deformity due to pyoderma gangrenosum using a
      Taylor spatial frame and tibiotalar calcaneal fusion with an intramedullary
      device.
AB  - Pyoderma gangrenosum is a rare autoinflammatory syndrome manifested by skin
      lesions eventually creating ulcers. Surgical management can lead to scarring and
      contracture at the site of the lesion due to the pathergy phenomenon. A 43-year
      old woman presented with a 5-year history of severe equinovarus deformity due to
      chronic pyoderma gangrenosum on her posteromedial ankle. She underwent a staged
      fusion. A gradual "closed" correction was performed in a Taylor spatial frame for
      8 weeks in order to obviate the need for a surgical release in the area of the
      ulcer. She was ambulatory and full weight-bearing within 4 weeks of her frame
      removal. She maintained her correction with an accommodative foot orthosis until
      she had an uneventful tibiotalar calcaneal fusion with an intramedullary device.
      This case represents the success of using a Taylor spatial frame for staged
      fusion involving soft-tissue correction of severe, rigid equinovarus deformity
      due to pyoderma gangrenosum.

PMID- 21863299
TI  - Necrotizing fasciitis of the extremities: a prospective study.
AB  - Necrotizing fasciitis is a rapidly progressive infection and is a necrosis of the
      fascia and surrounding tissues. Despite recent advances in its management,
      outcomes have not improved and mortality rate is still high. Between September
      2007 and August 2009, we prospectively studied twenty-four histopathologically
      proven necrotizing fasciitis patients to assess the prognostic factors that
      indicate the outcome. Mortality rate was 20.8%. Twelve patients (50%) improved,
      while seven patients (29.2%) were complicated by limb loss. Mortality rates
      related to upper and lower limb involvement were similar (20% vs. 22.2%). The
      rates of gangrene and amputation in patients with diabetes mellitus were
      significantly higher than other comorbidities. Patients with gram-positive
      infections had significantly lower rates of amputation (15.4% vs. 54.5%, P =
      0.04). Mean band cell count and serum potassium level were significantly higher
      in the nonsurvivors same as leukocyte count in the patients with gangrene, while
      serum sodium level was significantly lower in nonsurvivors. We conclude that
      hyponatremia, hyperkalemia, and increased band cells in the peripheral blood of
      patients may be useful parameters in distinguishing life-threatening necrotizing
      fasciitis; hence, we recommended lower threshold to amputation during surgery for
      this group of patients.

PMID- 21863300
TI  - AD: are we intervening too late?

PMID- 21863301
TI  - Excision of giant condyloma and V-Y flap reconstruction.

PMID- 21863302
TI  - Comparison of microbial hosts and expression systems for mammalian CYP1A1
      catalysis.
AB  - Mammalian cytochrome P450 enzymes are of special interest as biocatalysts for
      fine chemical and drug metabolite synthesis. In this study, the potential of
      different recombinant microorganisms expressing rat and human cyp1a1 genes is
      evaluated for such applications. The maximum specific activity for 7
      ethoxyresorufin O-deethylation and gene expression levels were used as parameters
      to judge biocatalyst performance. Under comparable conditions, E. coli is shown
      to be superior over the use of S. cerevisiae and P. putida as hosts for
      biocatalysis. Of all tested E. coli strains, E. coli DH5alpha and E. coli JM101
      harboring rat CYP1A1 showed the highest activities (0.43 and 0.42 U g-1(CDW),
      respectively). Detection of active CYP1A1 in cell-free E. coli extracts was found
      to be difficult and only for E. coli DH5alpha, expression levels could be
      determined (41 nmol g-1(CDW)). The presented results show that efficient
      expression of mammalian cyp1a1 genes in recombinant microorganisms is troublesome
      and host-dependent and that enhancing expression levels is crucial in order to
      obtain more efficient biocatalysts. Specific activities currently obtained are
      not sufficient yet for fine chemical production, but are sufficient for
      preparative-scale drug metabolite synthesis.

PMID- 21863303
TI  - Microcystic meningioma presenting as a cystic lesion with an enhancing mural
      nodule in elderly women: report of three cases.
AB  - Cystic meningioma with an enhancing mural nodule is uncommon and can present as a
      radiologic and clinical dilemma with wide differential. We report a series of
      rare and unique presentation of microcystic meningioma in three elderly women
      aged 76 (case 1), 72 (case 2), and 76 (case 3) years, respectively. The first
      patient presented with a 3-year history of vertigo and past history of carotid
      artery stenosis, hypertension, and hypothyroidism. The second patient presented
      with headache and an acute episode of weakness in her legs. The third patient
      presented with headache, vomiting, and confusion. Magnetic resonance imaging for
      these three cases showed a cystic lesion with an enhancing mural nodule in the
      right frontal lobe. The preoperative differential diagnoses included
      hemangioblastoma and well-circumscribed gliomas for the first two cases.
      Glioblastoma and metastatic tumor were the working diagnoses for the third case
      because of vasogenic brain edema and marked mass effect. The final pathological
      diagnosis was microcystic meningioma for all three cases. Case reports are mainly
      of fibrous or meningothelial meningiomas with cystic formation. Male predominance
      and young age are most commonly reported. Our series is unique because of the
      rare and unusual clinical-radiologic presentation of microcystic meningioma in
      elderly women.

PMID- 21863304
TI  - Knee kinematics: we need to know more.

PMID- 21863305
TI  - Tension band wire fixation for anterior cruciate ligament avulsion fracture:
      biomechanical comparison of four fixation techniques.
AB  - PURPOSE: The purpose of this study is to design a new fixation method to treat
      tibial eminence fractures and assess its stability compared with conventional
      fixation methods. METHODS: Eighty fresh porcine knees were stripped of all soft
      tissue, leaving intact only the femur-anterior cruciate ligament (ACL)-tibia
      complex. A standardized type III fracture was simulated at the anterior cruciate
      ligament attachment region using an osteotome. Then, the 80 specimens were
      randomly divided into 4 groups consisting of 20 knees each. The bony fragments
      were, respectively, fixed with sutures, steel wire, screws, and the newly
      designed tension band wire. All specimens were subsequently tested on a Material
      Testing Machine at a load rate of 60 mm/min. The statistically significant
      difference between the methods in terms of ultimate failure load, yield load, and
      displacement of the fragment under single-cycle loading and cyclic loading were
      analysed. RESULTS: Steel wire encircling K-wire fixation showed significantly
      higher maximum loads, yield loads, and less displacement than all the other
      fixation methods tested. Specimens fixed with steel wire had the second highest
      maximal load followed by fixation with the cannulated screw. The lowest maximal
      load was observed in the group using PDS II suture. CONCLUSIONS: The ultimate
      strength of tension band wire fixation of tibial eminence fractures in these
      specimens was significantly greater than those of the other three fixation
      methods. Tension band wire fixation of eminence fractures appears to provide
      biomechanical advantages over the other three fixation methods; hence, it is a
      practical alternative to conventional fixation techniques.

PMID- 21863306
TI  - A new technique for arthroscopic meniscus transplant using soft tissue fixation
      and anatomical meniscal root reinsertion.
AB  - Allograft meniscus transplant is considered as a treatment option for meniscus
      deficient patients to provide pain relief and decrease contact stress. This
      procedure is now considered as safe and reliable for the treatment for knee pain
      after total menisectomy. This is a new technique that has been developed for
      arthroscopic meniscus transplant with no bone blocks. It anatomically recreates
      the meniscus-tibial insertions and provides aperture fixation of the meniscus
      horns. It is an alternative to the established bone block meniscus transplant
      technique and is less surgically invasive. LEVEL OF EVIDENCE: V.

PMID- 21863307
TI  - Streptococcus gallolyticus prosthetic joint infection associated with undiagnosed
      colonic malignancy.
AB  - Streptococcus gallolyticus is a group D streptococcus which was previously
      classified as part of the S. bovis/S. equinus complex. It is a rare pathogen in
      prosthetic joint infection but has been demonstrated to have a strong association
      with colorectal carcinoma. In this case, a patient with no symptomatology
      suggestive of colorectal carcinoma presented with a S. gallolyticus prosthetic
      joint infection. Awareness of the association prompted investigation and
      subsequent diagnosis of colorectal carcinoma which was successfully treated prior
      to two-stage revision knee replacement. LEVEL OF EVIDENCE: V.

PMID- 21863309
TI  - A lower dose of docetaxel at 60 mg/m(2) could be continued longer for controlling
      peripheral edema in patients with metastatic breast cancer.
AB  - BACKGROUND: Docetaxel is a key drug for metastatic breast cancer (MBC). In
      patients with MBC, the treatment objective is durable response with minimum
      toxicity. In Japan, the approved dose of docetaxel is 60-70 mg/m(2) every 3
      weeks, whereas 75-100 mg/m(2) docetaxel is common in the West. METHODS: We
      retrospectively examined the prevalence of edema in patients with MBC who were
      treated with docetaxel. Seventy-seven patients received docetaxel at a dose of 60
      mg/m(2) every 3 weeks with prophylactic premedication of dexamethasone, 8 mg
      daily for 3 days. RESULTS: Median follow-up time was 28 months (range 4.3-98).
      Overall response was 25% (95% CI 15-34). Median time to progression and median
      survival time from the beginning of any systemic therapy for metastatic disease
      were 10 and 66 months, respectively. Neutropenia was the most common toxicity,
      with grade 3-4 observed in 66%. Fifty-one percent of the patients experienced
      peripheral edema that could be controlled with oral diuretics. Grade 3 edema was
      observed in 4 patients only, and discontinuation because of edema was 9%. Other
      grade 3 or 4 toxicity was <5%. Median cumulative dose of docetaxel to onset of
      peripheral edema was 480 mg/m(2) (range 60-780), and median cumulative given dose
      was 600 mg/m(2) (range 84-2,928). CONCLUSIONS: These results suggest that
      treatment with docetaxel at 60 mg/m(2) could be continued longer than the higher
      dose with manageable peripheral edema in patients with MBC. Further investigation
      is required to determine the superiority of low-dose docetaxel.

PMID- 21863308
TI  - Hepatic stellate cells produce vascular endothelial growth factor via phospho
      p44/42 mitogen-activated protein kinase/cyclooxygenase-2 pathway.
AB  - Vascular endothelial growth factor (VEGF) is one of the major cytokines secreted
      by activated hepatic stellate cells (HSCs). VEGF is involved in hepatic
      angiogenesis and plays an important role in the development of liver fibrosis.
      TNP-470, an angiogenic inhibitor, attenuates the development of rat liver
      fibrosis with reduced angiogenesis, as demonstrated in our previous study. HSCs
      were prepared from specific pathogen-free Wister rat livers. The isolated HSCs
      were activated and stimulated with platelet-derived growth factor BB (PDGF-BB) or
      prostaglandin E2 with or without pretreatment with MAPK cascade inhibitors
      (PD98059, which inhibits MEK activation), SB203580 (a selective pharmacologic
      inhibitor of p38 MAPK), and SP600125 (a selective inhibitor of the c-Jun N
      terminal kinase, JNK). VEGF production and those of related molecules were
      assayed at the protein and mRNA levels by immunostaining, western blot analysis,
      and real-time quantitative PCR. The activated HSCs produced more VEGF than the
      quiescent ones. Those that received PDGF-BB stimulation showed enhanced
      cyclooxygenase-2 (COX-2) expression and activation of phosphor-mitogen-activated
      protein kinase (MAPK) p44/p42. Pretreatment with PD98059 significantly inhibited
      COX-2 expression and VEGF production within the PDGF-activated HSCs, but the
      effect was nullified by exogenous prostaglandin E2. pJNK and p38 inhibitors do
      not show similar inhibitory effects on VEGF and COX-2 expression, and pJNK and
      p38 MAPK signals are not involved in the COX-2/MAPK signaling cascade. VEGF
      production in PDGF-stimulated HSCs is dependent on the overexpression of COX-2
      protein via the phospho-p42/44 MAP kinase activation, based on PD98059
      inhibition.

PMID- 21863310
TI  - Possible available treatment option for early stage, small, node-negative, and
      HER2-overexpressing breast cancer.
AB  - Trastuzumab is known for its clinical activity in women with HER2-overexpressing
      breast cancer. Randomized clinical trials have shown significant improvement in
      disease-free and overall survival with trastuzumab administered in conjunction
      with adjuvant chemotherapy for early-stage HER2-positive breast cancer. However,
      there is no direct evidence of clinical benefit from adjuvant trastuzumab in
      patients with node-negative, HER2-overexpressing, small (T1a-b) breast cancers.
      Previous literature shows that most breast cancers with node-negative small
      tumors have a good prognosis, but HER2-overexpressing disease might still be
      worse in this population. Some recent retrospective studies showed that an
      adjuvant trastuzumab-based regimen has a better prognostic effect, even in
      patients with node-negative, HER2-overexpressing, small breast cancers, although
      absolute survival differences were small. On the basis of the available
      literature, we believe that trastuzumab should be considered for patients with
      minimal HER2-overexpressing disease, although tools for accurate selection of
      patients at risk of relapse still need to be developed.

PMID- 21863311
TI  - Endometrial/uterine corporeal volume ratio (EV/UCV) as predictor of malignancy in
      women with postmenopausal bleeding.
AB  - OBJECTIVE: To evaluate the role of endometrial/uterine corporeal volume ratio for
      the prediction of endometrial malignancy in cases of postmenopausal bleeding.
      METHODS: Endometrial volumes and uterine body volumes excluding cervices measured
      by VOCAL (virtual organ computer-aided analysis) were estimated in 160 women with
      postmenopausal bleeding. Endometrial/uterine corporeal volume ratios were
      calculated for all. Endometrial biopsies and histopathological results were
      obtained for all. One hundred normal postmenopausal women were included as
      controls. RESULTS: Histopathological results of the 160 women with postmenopausal
      bleeding revealed 53 atypia, 27 endometrial cancer and 80 benign conditions. An
      endometrial/uterine volume (EV/UCV) ratio of a cutoff value >0.017 was predictive
      of malignancy. Endometrial/uterine volume ratio was more sensitive than
      endometrial volume and endometrial thickness for prediction of endometrial
      cancer. CONCLUSION: An endometrial/uterine volume ratio (EV/UCV) >0.017 is
      predictive of malignancy. (EV/UCV) was more accurate in the prediction of
      malignancy than endometrial thickness and endometrial volume.

PMID- 21863312
TI  - Cellular signatures in the primary visual cortex of phylogeny and placentation.
AB  - The long-held view that brain size can be used as an index of general functional
      capacity across mammals is in conflict with increasing evidence for phyletic
      differences in cellular organization. Furthermore, it is poorly understood how
      the internal cellular organization of the brain covaries with overall brain size
      variation. Using design-based stereology, we quantified glial cell and neuronal
      densities in the primary visual cortex of 71 mammalian species (spanning 11
      orders) to test how those cellular densities are influenced by phylogeny,
      behavior, environment, and anatomy. We further tested cellular densities against
      mode of placentation to determine whether a relationship may exist. We provide
      evidence for cellular signatures of phylogenetic divergence from the mammalian
      trend in primates and carnivores, as well as considerably divergent scaling
      patterns between the primate suborders, Strepsirrhini and Haplorrhini, that
      likely originated at the anthropoid stem. Finally, we show that cellular
      densities in the mammalian cortex relate to the variability of maternal resources
      to the fetus in a species.

PMID- 21863313
TI  - A shift to 50 degrees C provokes death in distinct ways for glucose- and oleate
      grown cells of Yarrowia lipolytica.
AB  - Based on the observation that shocks provoked by heat or amphiphilic compounds
      present some similarities, this work aims at studying whether cells grown on
      oleate (amphiphilic pre-stress) acquire a tolerance to heat shock. In rich media,
      changing glucose for oleate significantly enhanced the cell resistance to the
      shock, however, cells grown on a minimal oleate medium lost their ability to grow
      on agar with the same kinetic than glucose-grown cells (more than 7-log decrease
      in 18 min compared with 3-log for oleate-grown cells). Despite this difference in
      kinetics, the sequence of events was similar for oleate-grown cells maintained at
      50 degrees C with a (1) loss of ability to form colonies at 27 degrees C, (2)
      loss of membrane integrity and (3) lysis (observed only for some minimal-oleate
      grown cells). Glucose-grown cells underwent different changes. Their membranes,
      which were less fluid, lost their integrity as well and cells were rapidly
      inactivated. But, surprisingly, their nuclear DNA was not stained by propidium
      iodide and other cationic fluorescent DNA-specific probes but became stainable by
      hydrophobic ones. Moreover, they underwent a dramatic increase in membrane
      viscosity. The evolution of lipid bodies during the heat shock depended also on
      the growth medium. In glucose-grown cells, they seemed to coalesce with the
      nuclear membrane whereas for oleate-grown cells, they coalesced together forming
      big droplets which could be released in the medium. In some rare cases of oleate
      grown cells, lipid bodies were fragmented and occupied all the cell volume. These
      results show that heat triggers programmed cell death with uncommon hallmarks for
      glucose-grown cells and necrosis for methyl-oleate-grown cells.

PMID- 21863314
TI  - Local delivery of FTY720 accelerates cranial allograft incorporation and bone
      formation.
AB  - Endogenous stem cell recruitment to the site of skeletal injury is key to
      enhanced osseous remodeling and neovascularization. To this end, this study
      utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA)
      to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate
      (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated,
      low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were
      implanted into critical size calvarial bone defects. The ability of local FTY720
      delivery to promote angiogenesis, maximize osteoinductivity and improve allograft
      incorporation by recruitment of bone progenitor cells from surrounding soft
      tissues and microcirculation was evaluated. FTY720 bioactivity after
      encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS
      quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5
      MUg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to
      statistically significant increases in bone volumes compared to controls, with
      total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of
      5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone
      growth persisted through week 4 but, by week 8, increases in bone formation in
      FTY720 groups were no longer statistically significant. However, micro-computed
      tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL(r)) and
      histological analysis showed enhanced integration as well as directed bone growth
      in both high and low dose FTY720 groups compared to controls.

PMID- 21863315
TI  - Quantification of gene expression after painful nerve injury: validation of
      optimal reference genes.
AB  - Stably expressed housekeeping genes (HKGs) are necessary for standardization of
      transcript measurement by quantitative real-time polymerase chain reaction (qRT
      PCR). Peripheral nerve injury disrupts expression of numerous genes in sensory
      neurons, but the stability of conventional HKGs has not been tested in this
      context. We examined the stability of candidate HKGs during nerve injury,
      including the commonly used 18S ribosomal RNA, beta-tubulin I and beta-tubulin
      III, actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and hypoxanthine
      phosphoribosyltransferase 1 (HPRT1), and mitogen-activated protein kinase 6
      (MAPK6). Total RNA for cDNA synthesis was isolated from dorsal root ganglia of
      rats at 3, 7, and 21 days following either skin incision alone or spinal nerve
      ligation, after which the axotomized and adjacent ganglia were analyzed
      separately. Relative stability of HKGs was determined using statistical
      algorithms geNorm and NormFinder. Both analyses identified MAPK6 and GAPDH as the
      two most stable HKGs for normalizing gene expression for qRT-PCR analysis in the
      context of peripheral nerve injury. Our findings indicate that a prior analysis
      of HKG expression levels is important for accurate normalization of gene
      expression in models of nerve injury.

PMID- 21863316
TI  - Symmetrical corticobasal syndrome caused by a novel C.314dup progranulin
      mutation.
AB  - Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and
      cognitive impairment. The underlying pathology varies between corticobasal
      degeneration, progressive supranuclear palsy, Alzheimer's disease, Creutzfeldt
      Jakob disease and frontotemporal lobar degeneration sometimes in association with
      GRN mutations. A 61-year-old male underwent neurological examination,
      neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After
      his death at the age of 63, brain autopsy, genetic screening and mRNA expression
      analysis were performed. The patient presented with slow progressive walking
      disabilities, non-fluent language problems, behavioural changes and
      forgetfulness. His family history was negative. He had primitive reflexes,
      rigidity of his arms and postural instability. Later in the disease course he
      developed dystonia of his left leg, pathological crying, mutism and dysphagia.
      Neuropsychological assessment revealed prominent ideomotor and ideational
      apraxia, executive dysfunction, non-fluent aphasia and memory deficits.
      Neuroimaging showed symmetrical predominant frontoparietal atrophy and
      hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was
      found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup,
      p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN
      mutation in a patient with an atypical (CBS) presentation with symmetric
      neuroimaging findings. GRN mutations are an important cause of CBS associated
      with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN
      mutations should also be considered in CBS patients without a positive family
      history.

PMID- 21863318
TI  - Symptomatic myocarditis in Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute febrile illness of infants and young children
      that is characterized by a medium vessel vasculitis, most commonly involving the
      coronary arteries. Though subclinical myocarditis is rather common in KD,
      symptomatic congestive heart failure is extremely uncommon. The authors report a
      9-y-old boy who developed heart failure (ejection fraction 28%) in the acute
      phase of KD. He was initially treated with intravenous immunoglobulin (2 g/kg)
      without much clinical improvement. He was then given 5 daily pulses of
      intravenous methylprednisolone followed by tapering doses of oral prednisolone.
      The child showed prompt clinical recovery and remains well on follow-up. The
      present case serves to highlight the fact that methylprednisolone can be
      considered upfront as rescue therapy in children with KD who have symptomatic
      congestive cardiac failure during the acute stage of the disease.

PMID- 21863319
TI  - A simulation study of TaMAC protocol using network simulator 2.
AB  - A Wireless Body Area Network (WBAN) is expected to play a significant role in
      future healthcare system. It interconnects low-cost and intelligent sensor nodes
      in, on, or around a human body to serve a variety of medical applications. It can
      be used to diagnose and treat patients with chronic diseases such as
      hypertensions, diabetes, and cardiovascular diseases. The lightweight sensor
      nodes integrated in WBAN require low-power operation, which can be achieved using
      different optimization techniques. We introduce a Traffic-adaptive MAC protocol
      (TaMAC) for WBAN that supports dual wakeup mechanisms for normal, emergency, and
      on-demand traffic. In this letter, the TaMAC protocol is simulated using a well
      known Network Simulator 2 (NS-2). The problem of multiple emergency nodes is
      solved using both wakeup radio and CSMA/CA protocol. The power consumption,
      delay, and throughput performance are closely compared with beacon-enabled IEEE
      802.15.4 MAC protocol using extensive simulations.

PMID- 21863317
TI  - Progranulin and TDP-43: mechanistic links and future directions.
AB  - Loss-of-function mutations in the multifunctional growth factor progranulin (GRN)
      cause frontotemporal lobar degeneration (FTLD) with TDP-43 protein accumulation.
      Nuclear TDP-43 protein with key roles in RNA metabolism is also aggregated in
      amyotrophic lateral sclerosis (ALS), suggesting that ALS and FTLD constitute a
      broad disease continuum. However, the fact that mutations in GRN are associated
      with FTLD, while mutations in TDP-43 cause a preferential loss of motor neurons
      resulting in ALS-end of the disease spectrum, suggests involvement of both cell
      autonomous and non-autonomous mechanisms. Studies on animal models and in vitro
      studies have been instrumental in understanding the link between GRN and TDP-43
      and also their role in neurodegeneration. For instance, in mouse models, allelic
      deficiencies of Grn do not recapitulate human pathology of TDP-43 brain
      accumulations, but embryonic neurons derived from these mice do show abnormal TDP
      43 accumulation after additional cellular challenges, suggesting that TDP-43
      changes observed in GRN mutation carriers might also relate to stress. Recent
      results have shown that the dual action of GRN in growth modulation and
      inflammation could be due to its negative regulation of TNF-alpha signaling. In
      addition, GRN also interacts with sortilin and is endocytosed, thereby regulating
      its own levels and possibly also modulating the turnover of other proteins
      including that of TDP-43. Accumulating evidence suggests that TDP-43 abnormal
      cellular aggregation causes a possible gain of function, also suggested by
      recently constructed mouse models of TDP-43 proteinopathy; however, it would be
      inconvincible that sequestration of physiological TDP-43 within cellular
      aggregates observed in patients would be innocuous for disease pathogenesis. This
      review discusses some of these data on the possible link between GRN and TDP-43
      as well as mechanisms involved in TDP-43-led neurodegeneration. Continued
      multitiered efforts on genetic, cell biological, and animal modeling approaches
      would prove crucial in finding a cure for GRN-related diseases.

PMID- 21863320
TI  - Correlation of angiographic late loss with neointimal coverage of drug-eluting
      stent struts on follow-up optical coherence tomography.
AB  - Minimal data have been published on the correlation between angiographic late
      loss (LL) and incomplete neointimal coverage of struts after drug-eluting stent
      (DES) implantation. Therefore, we evaluated the relationship between angiographic
      LL and the percentage of uncovered struts on follow-up optical coherence
      tomography (OCT) images, in all cross-sections of the lesions. From the OCT
      registry database, 219 lesions without restenosis after DES implantation were
      divided into tertiles based on angiographic LL: tertile I (LL <= 0.26 mm),
      tertile II (0.26 < LL < 0.59 mm), and tertile III (>=0.59 mm). Lesions with the
      percentage of uncovered struts in the highest quartile (>=75th percentile; >6.0%)
      were defined as highly uncovered; in an independent analysis, lesions without any
      uncovered strut(s) were defined as completely covered. Higher percentages of
      uncovered struts were observed in tertile I than in both tertile II and III (10.3
      +/- 12.8% vs. 4.2 +/- 7.4% vs. 2.4 +/- 5.1%, respectively; P < 0.001 for I vs. II
      and I vs. III). Angiographic LL correlated significantly with the percentage of
      uncovered struts on OCT (r = -0.340, P < 0.001). The best cut-off values of
      angiographic LL to predict highly uncovered and completely covered lesions were
      0.29 mm (area under curves [AUC] = 0.723, P < 0.001) and 0.61 mm (AUC = 0.692, P
      < 0.001), respectively. Angiographic LL inversely and significantly correlated
      with the percentage of uncovered struts on OCT after DES implantation.

PMID- 21863321
TI  - Effect of alcohol septal ablation in patients with hypertrophic cardiomyopathy on
      left-ventricular mechanical dyssynchrony as assessed by phase analysis of gated
      SPECT myocardial perfusion imaging.
AB  - Patients with hypertrophic cardiomyopathy (HCM) may have delayed septal
      activation and left ventricular (LV) mechanical dyssynchrony, and may improve
      after alcohol septal ablation (ASA). This study used phase analysis of gated
      SPECT myocardial perfusion imaging (MPI) to evaluate septal activation and LV
      dyssynchrony in HCM patients pre- and post-ASA. Phase analysis was applied to 28
      controls, and 32 HCM patients having rest MPI pre- and post-ASA to assess septal
      lateral mechanical activation delay (SLD) and consequent LV dyssynchrony. In
      addition, phase analysis was applied to another group of 30 patients having
      serial MPI to measure variability of the LV dyssynchrony parameters on serial
      studies. ASA significantly reduced SLD and improved LV synchrony in the HCM
      patients with SLD < 0 degrees  due to earlier activation of the lateral wall
      relative to the septum. Based on the measured variability, 12 HCM patients had
      significant (Z < -1.65, P < 0.05) and 4 had moderate (Z < -1.00, P < 0.15)
      improvement in LV synchrony post-ASA. SLD < 0 degrees  predicted improvement in
      LV synchrony after ASA with a sensitivity of 81% and a specificity of 88%. SLD
      and LV dyssynchrony were frequent in HCM patients. HCM patients, whose septal
      activation became later than lateral activation, had significant reduction in
      septal activation delay and improvement in LV synchrony after ASA.

PMID- 21863322
TI  - Liquefaction necrosis of mitral annular calcification (LNMAC): review of
      pathology, prevalence, imaging and management: proposed diagnostic imaging
      criteria with detailed multi-modality and MRI image characterization.
AB  - Liquefactive necrosis within a large spheroid zone of mitral annular
      calcification (LNMAC) is an atypical but increasingly recognized variant of
      mitral annular calcification (MAC). Proposed MRI, echo, and CT imaging criteria
      for diagnosis of this unusual disease entity are discussed along with a review of
      the prognosis, histopathology, and management implications. A comprehensive ECHO,
      CT, and MRI imaging approach to diagnostic differentiation from other cardiac
      masses, allowing characterization of the differing components of this unusual
      lesion is emphasized. Differentiation from surrounding myocardium, and
      demonstration of peripheral ring type hyperenhancement, or hyperintense signal in
      the wall of this lesion, seen with specific inversion recovery MRI sequences is
      presented as a major diagnostic criterion. The relationship of these MRI image
      findings to underlying pathology is also discussed. An illustrative case vignette
      is provided for clinical reference.

PMID- 21863323
TI  - Selenium regulates gene expression of selenoprotein W in chicken gastrointestinal
      tract.
AB  - Selenoprotein W (SelW) is an existing form of selenium (Se). Se influences the
      levels of SelW in mammals. However, little is known about the pattern of SelW
      expression in the gastrointestinal tract tissue of bird. The present paper
      describes the effects of different dietary levels of Se on the SelW mRNA
      expression in the gastrointestinal tract tissue of chicken. The expression levels
      of SelW mRNA and the Se contents in the gastrointestinal tract tissues (glandular
      stomach, gizzard, duodenum, small intestine, and rectum) were determined on days
      15, 25, 35, 45, and 55, respectively. The results showed that the Se contents and
      the SelW mRNA expression were significantly higher (p < 0.05) in the high-Se
      group, and the Se contents and SelW mRNA expression in the low-Se group were
      significantly lower (p < 0.05) than in the controls. The Se contents were the
      highest in the duodenum and the lowest in the rectum, while the SelW mRNA
      expression was the highest in the gizzard and the lowest in the rectum. In
      addition, the SelW mRNA levels in the gastrointestinal tract tissue were found to
      increase in a time-dependent manner with increasing feeding time. Furthermore,
      the expression of the SelW mRNA in the gastrointestinal tract tissues of chickens
      was found to correlate with the dietary Se concentrations, but not with the
      tissue Se contents.

PMID- 21863324
TI  - Estimating intestinal absorption of inorganic and organic selenium compounds by
      in vitro flux and biotransformation studies in Caco-2 cells and ICP-MS detection.
AB  - The aim of the present work was to compare and estimate absorption and
      biotransformation of selected selenium compounds by studying their fluxes across
      Caco-2 cells. Five different selenium compounds, selenomethionine (SeMet), Se
      methylselenocysteine (MeSeCys), selenate, selenite, and methylseleninic acid
      (MeSeA), were applied to Caco-2 cells in a concentration of 10 MUM, and fluxes in
      both directions were studied for 2 h. Fluxes of selenite and MeSeA in the
      presence of excess reduced glutathione (selenite + GSH and MeSeA + GSH) and flux
      of MeSeA in the presence of excess cysteine (MeSeA + Cys) were also studied.
      Selenium absorptive and exsorptive fluxes and accumulation in cell cytosol were
      analyzed by means of flow injection inductively coupled plasma mass spectrometry
      (ICP-MS). Absorptive flux of SeMet, MeSeCys, and selenate showed values
      correlating to complete in vivo absorption, while selenite and MeSeA fluxes
      correlated to poor in vivo absorption. Speciation analysis of cell lysate and
      donor and receptor solutions by LC-ICP-MS showed limited transformation of all
      selenium compounds. Extensive transformation as well as significantly increased
      absorptive flux was observed when co-administering selenite with glutathione
      compared to administering selenite alone. These observations are possibly due to
      formation of selenodiglutathione (GS-Se-SG) which may be absorbed differently
      than selenite. Concomitant application of GSH or cysteine with MeSeA resulted in
      extensive transformation of MeSeA, including volatile species, whereas no
      significant increases in fluxes were observed. In summary, the absorption of
      selenite selenate and the selenoamino acids is considered complete under
      physiological conditions, but the absorption mechanisms and metabolism of the
      compounds are different.

PMID- 21863325
TI  - Unique growth pattern in papillary carcinoma of the thyroid gland mimicking
      adenoid cystic carcinoma.
AB  - We report here three cases of papillary thyroid carcinoma (PTC) with hyaline
      globules as seen in adenoid cystic carcinoma of the salivary glands. This unique
      growth pattern was seen in two cases of columnar cell and one case of cribriform
      morular variant of PTC. Fine-needle aspiration was performed in two cases. By
      immunohistochemistry, all cases demonstrated expression of TTF-1 and
      thyroglobulin confirming follicular cell derivation. It is important to be aware
      of this unusual growth pattern in thyroid carcinomas; immunohistochemistry is
      warranted for rendering accurate cytopathologic and histopathologic diagnosis.

PMID- 21863326
TI  - Churg-strauss syndrome: an update.
AB  - Churg-Strauss syndrome is an uncommon disease of unknown cause described
      initially by Churg and Strauss in 1951. Even though it was initially thought to
      be a variant of polyarteritis nodosa, its pathological, clinical, and laboratory
      features show that it is related to the small vessel vasculitides, and it is now
      classified as an antineutrophil cytoplasmic antibody-associated vasculitis. The
      presence of asthma, usually of adult onset, along with other allergic symptoms,
      peripheral and tissue eosinophilia, is specific to this disease. These features
      usually help clinicians distinguish it from other types of small vessel
      vasculitis and should alert clinicians about its presence. Two different clinical
      subtypes defined by the presence of antineutrophil cytoplasmic antibodies
      recently have been recognized. Recent advances in the treatment and
      pathophysiology of Churg-Strauss syndrome are reviewed in this article.

PMID- 21863327
TI  - Enantioselective preference and high antennal sensitivity for (-)-Ipsdienol in
      scent-collecting male orchid bees, Euglossa cyanura.
AB  - Male neotropical orchid bees (Euglossini) collect volatile chemicals from their
      environment, store them in tibial pouches, and later expose their "perfumes"
      during a courtship display. Here, we showed that enantiomeric selectivity plays
      an important role in the choice of volatiles by male Euglossa cyanura in southern
      Mexico, and that behavioral selectivity is linked to antennal sensitivity. In
      field bioassays with equal concentrations of (+)-ipsdienol, (-)-ipsdienol, and
      racemate, males preferred the (-)-isomer to the racemate, while neglecting the
      (+)-isomer. Correspondingly, antennae of male E. cyanura showed larger
      electroantennographic responses to the (-)-isomer than to the (+)-isomer. In
      comparison, antennae of male Euglossa mixta, which are not attracted to any form
      of ipsdienol, showed lower electroantennographic responses to (-)-ipsdienol than
      did antennae of E. cyanura, and also did not differ in sensitivity with respect
      to the (+)- or (-)-isomers. We suggest that (-)-ipsdienol is an important
      component of perfume signals in male E. cyanura, which have undergone selection
      in favor of increased antennal sensitivity to that enantiomer.

PMID- 21863328
TI  - Tissue distribution and expression of signaling lymphocyte activation molecule
      receptor to peste des petits ruminant virus in goats detected by real-time PCR.
AB  - In the present study, we investigated the tissue distribution and expression of
      signaling lymphocyte activation molecule (SLAM) in 40 tissues and organs of goats
      by real-time RT-PCR, in order to determine the role of these receptors in tissue
      tropism. SLAM mRNA was detected in all the samples investigated. The expression
      of SLAM mRNA was detected at high levels in spleen, mesenteric lymph node, hilar
      lymph node, mandibular lymph node, superficial cervical lymph node, nasal mucosa,
      duodenum, heart, gallbladder, thymus and blood; this is similar to the tissue
      tropism of peste des petits ruminant virus. However, it was surprising that
      expression of SLAM was low in lungs, colon and rectum which are the major sites
      of replication of PPRV. In addition, very low levels were detected in larynx,
      tongue and esophagus, which suggest the possible presence of an alternative
      receptor for PPRV. This study provided the first data on caprine SLAM for use in
      further studies of the pathogenesis of PPRV in goats.

PMID- 21863329
TI  - Etanercept attenuates TNBS-induced experimental colitis: role of TNF-alpha
      expression.
AB  - Crohn's disease (CD) is associated with gut barrier dysfunction. Tumour necrosis
      factor-alpha (TNF-alpha) plays an important role into the pathogenesis of several
      inflammatory diseases because its expression is increased in inflamed mucosa of
      CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus,
      this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis
      factor alpha (TNF-alpha) antagonist on the 2,4,6-trinitrobenzene sulfonic acid
      (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized
      into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non
      treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats
      from group 4 presented significant improvement either of macroscopic or of
      histopathological damage in the distal colon. The gene expression of TNF-alpha
      mRNA, decreased significantly in this group compared to the TNBS non-treated
      group. The treatment with etanercept attenuated the colonic damages and reduced
      the inflammation caused by TNBS. Taken together, our results suggest that ETC
      attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-alpha
      downregulation.

PMID- 21863330
TI  - Isn't it time to stop talking about colonoscopy quality and start doing something
      about it?

PMID- 21863331
TI  - Alcohol screening and brief intervention among drug users in primary care: a
      discussion paper.
AB  - BACKGROUND: Problem alcohol use is common among problem drug users (PDU) and
      associated with adverse health outcomes. Primary care has an important role in
      the overall stepped approach to alcohol treatment, especially screening and brief
      intervention (SBI). AIM: To discuss three themes that emerged from an exploration
      of the literature on SBI for problem alcohol use in drug users attending primary
      care. METHODS: Material for this discussion paper was gathered from three
      biomedical databases (PubMed, PsycINFO and Cochrane library), conference
      proceedings and online resources of professional organisations or national health
      agencies. RESULTS: Themes discussed in this paper are: (a) the potential of
      primary care for delivery of alcohol SBIs to PDUs, (b) screening methods and (c)
      application of brief interventions to PDUs. CONCLUSIONS: Although SBI improves
      health outcomes associated with problem alcohol use in the general population,
      further research is needed among high-risk patient groups, especially PDUs.

PMID- 21863332
TI  - Dabigitran and the radiology department.

PMID- 21863334
TI  - Depressive symptoms, stress and resources among adult immigrants living with HIV.
AB  - Investigation on the mental health of HIV-positive immigrants is severely
      limited. We examine the independent and combined effects of HIV symptom and
      coping resources on depressive symptoms among HIV-positive immigrants (n = 259).
      Ordinary Least Squares regression models were estimated with data from a survey
      of clinical and social-psychological outcomes in people receiving treatment for
      HIV infection. We tested for the impact of two HIV-related stressors, one life
      events stressor and three buffering resources on depressive symptoms, controlling
      for thirteen demographic, clinical and acculturative factors. HIV-related
      stressors were found to be positively related to depressive symptom severity.
      Coping resources, namely self-mastery, mediate the relationships between HIV
      related stressors and depressive symptoms. Results from this study provide the
      first empirical assessment of stress processes for immigrants living with HIV.
      Although more research is needed to understand mental health among HIV-positive
      immigrants, the study results suggest that health care providers focus on self
      mastery enhancement among HIV-positive immigrants.

PMID- 21863335
TI  - Physical examination of potential tissue donors: results of a risk management
      procedure to identify the critical elements of the physical examination.
AB  - To identify critical elements of physical examination (PE) of potential tissue
      donors that could help to improve the safety of tissue transplantation. Physical
      signs were identified that can indicate the presence of a contraindication
      mentioned in EU Directive 2006/17/EC and that can theoretically be detected at
      PE. A risk assessment was designed, according to the Failure Mode and Effects
      Analysis model. Signs were scored on several aspects, taking into account various
      control measures, either required in the EU Directive or additional non-required
      measures. 106 signs associated with general and tissue-specific contraindications
      were identified. Signs of advanced infection with HIV, hepatitis B/C and syphilis
      (n = 13, 12.3%) can be omitted, since these contraindications will be detected by
      the required serological testing. With the required control measures, risk
      priorities are unacceptably "high" for 17.3% of the signs. For 64.5% of the
      signs, additional control measures are possible, which result in acceptable risk
      priorities for all signs. This risk management procedure identified the minimal
      necessary content of PE in potential tissue donors. Furthermore, risks associated
      with tissue donation were elucidated and possible risk control measures were
      identified as well as their impact on the safety of tissue transplantation.

PMID- 21863333
TI  - Effects of low environmental salinity on the cellular profiles and expression of
      Na+, K+-ATPase and Na+, K+, 2Cl- cotransporter 1 of branchial mitochondrion-rich
      cells in the juvenile marine fish Monodactylus argenteus.
AB  - The goal of this study was to determine the osmoregulatory ability of a juvenile
      marine fish, silver moony (Monodactylus argenteus), for the purpose of developing
      a new experimental species for ecophysiological research. In this study, M.
      argenteus was acclimated to freshwater (FW), brackish water (BW), or seawater
      (SW). The salinity tolerance of this euryhaline species was effective, and the
      fish survived well upon osmotic challenges. The largest apical surface of
      mitochondrion-rich cells was found in the FW individuals. Immunohistochemical
      staining revealed that Na(+), K(+)-ATPase immunoreactive (NKA-IR) cells were
      distributed in the interlamellar region of the gill filaments of the silver moony
      in all experimental groups. In addition to the filaments, NKA-IR cells were also
      found in the lamellae of the FW individuals. The number of NKA-IR cells in the
      gills of the FW individuals exceeded that of the BW and SW individuals. The NKA
      IR cells of FW and SW individuals exhibited bigger size than that of BW fish. The
      NKA activities and protein expression of the NKA alpha-subunit in the gills of
      the FW individuals were significantly higher than in the BW and SW groups.
      Additionally, the relative amounts of Na(+), K(+), 2Cl(-) cotransporter 1 (NKCC1)
      were salinity-dependent in the gills. Immunofluorescent signals of NKCC1 were
      localized to the basolateral membrane of NKA-IR cells in all groups. In the gills
      of the FW individuals, however, some NKA-IR cells did not exhibit a basolateral
      NKCC1 signal. In conclusion, the present study illustrated the osmoregulatory
      mechanisms of this easy- and economic-to-rear marine teleost with euryhaline
      capacity and proved the silver moony to be a good experimental animal.

PMID- 21863336
TI  - The impact of gene-environment interaction and correlation on the interpretation
      of heritability.
AB  - The presence of gene-environment statistical interaction (GxE) and correlation
      (rGE) in biological development has led both practitioners and philosophers of
      science to question the legitimacy of heritability estimates. The paper offers a
      novel approach to assess the impact of GxE and rGE on the way genetic and
      environmental causation can be partitioned. A probabilistic framework is
      developed, based on a quantitative genetic model that incorporates GxE and rGE,
      offering a rigorous way of interpreting heritability estimates. Specifically,
      given an estimate of heritability and the variance components associated with
      estimates of GxE and rGE, I arrive at a probabilistic account of the relative
      effect of genes and environment.

PMID- 21863337
TI  - Experimental study of neutron-induced soft errors in modern cardiac pacemakers.
AB  - PURPOSE: Density of circuits and size reduction of microelectronic devices
      increase the sensitivity to natural terrestrial radiation environment.
      Atmospheric particles, mainly neutrons can cause non-destructive or destructive
      failures in most electronic circuits, including volatile static memories. The
      failure occurrence probability of a soft error in real life is very low. However,
      in the last few years, a safety alert had to be communicated to the physicians
      for a few defibrillator models potentially affected by background levels of
      atmospheric ionizing cosmic radiation. The aim of this study was to test in vitro
      a variety of currently available pacemakers exposed to experimental neutron
      irradiation. METHODS: The neutron irradiation at high flux fast neutron beam was
      performed using Cyclone facility, with the cyclotron of the University of Leuven,
      Belgium. The neutron energy spectrum was obtained with a peak around 20 mega
      electron volt (MeV) energy range from 3 to 50 MeV, and tests were performed at
      three fluence levels: 1E9, 5E9, and 1E10 neutrons/cm(2). RESULTS: A total of 14
      tests were conducted on 14 devices from four manufacturers. Following the test,
      the devices were functioning normally in eight cases. In six cases, the response
      at interrogation was a message on the programmer screen announcing an electrical
      reset. In all of these cases, the programmer reset command was activated and
      immediately restored normal functioning and programmability. For a same model,
      the electrical reset was present at high fluence (1E10 or/and 5E9 n/cm2) and not
      at the lower level (1E9 n/cm2). Obvious differences among manufacturers were
      shown in this small sample study. CONCLUSIONS: This experiment shows the
      sensibility of modern pacemakers to neutron-induced soft errors and effectiveness
      of backup reversion in response to irradiation. The lower neutron fluence
      associated with a positive test was used to propose the calculation of the very
      low soft error rate for the tested devices in real-life atmospheric radiation.

PMID- 21863338
TI  - "Tell Juliana": acceptability of the candidate microbicide VivaGel(r) and two
      placebo gels among ethnically diverse, sexually active young women participating
      in a phase 1 microbicide study.
AB  - This study assessed acceptability of the candidate microbicide VivaGel((r)) and
      two placebo gels among 61 sexually active young US and Puerto Rican women at
      three sites. Participants were randomly assigned to use one of the gels twice per
      day for 14 days. At trial completion, 59% of the women in the VivaGel((r)) group
      reported being likely to use the gel in the future, whereas 23% were unlikely to
      use it and 18% were undecided. Participants reported problems with all three
      gels, including the "universal" placebo containing hydroxyethyl cellulose (HEC).
      The most frequent complaints were leakage, interference with sexual behavior, and
      decreased sexual satisfaction. Some of the complaints are not new but remain
      unresolved. Women's perceived risk of HIV infection may determine whether the
      gels are used. Users also may want a choice of viscosity. Poor acceptability of
      vaginal microbicide formulations may result in poor adherence to gel use during
      efficacy trials and compromise validity of results.

PMID- 21863339
TI  - Preventive misconception as a motivation for participation and adherence in
      microbicide trials: evidence from female participants and male partners in Malawi
      and Zimbabwe.
AB  - This paper presents empirical data on motivation to join an HIV prevention trial
      of vaginal microbicide gels in Malawi and Zimbabwe, and participant assumption of
      a preventive misconception. Interviews were conducted with women participating in
      the trial and their male partners. Most of the female participants were able to
      adequately describe basic aspects of the trial design. HIV counseling and testing
      were primary reasons motivating women's participation, and male partners' support
      of the trial. 29% of women and 20% of men also provided indications of a
      preventive misconception, attributing gel use and trial participation to avoiding
      HIV infection.

PMID- 21863340
TI  - TSH receptor extracellular region mutations in thyroid functioning nodules:
      further evidence for the functional role of this region in the receptor
      activation.

PMID- 21863341
TI  - Case seminar: a young female with acute hyponatremia and a sellar mass.
AB  - In familial cases of combined pituitary hormone deficiency the most common
      mutations are that of Prophet of Pit 1 (PROP1) gene. PROP1 mutations are
      associated with deficiencies of growth hormone, thyrotropin, prolactin, and
      gonadotropins (follicle-stimulating hormone and luteinizing hormone), with
      evolving adrenocorticotropin (ACTH) deficiency in some cases. On imaging in most
      patients the pituitary gland is hypoplastic, but occasionally transient pituitary
      enlargement is found. We report a 22-year-old female initially diagnosed at age
      12 with familial hypopituitarism due to PROP1 mutation, who presented with coma
      and respiratory arrest (acute hyponatremia). She was urgently treated in
      Intensive Care Unit of Emergency Center with hypertonic saline and stress doses
      of hydrocortisone, which resulted in the fast increase of plasma osmolality
      resulting in the osmotic demyelination syndrome. Simultaneously and incidentally
      on computed tomography scan a large sellar and suprasellar mass were reported as
      possible Rathke's cleft cyst or craniopharyngioma. Once the patient was stable,
      ACTH deficiency was documented. She remained replaced with hydrocortisone and
      subsequently underwent transphenoidal surgery. The removed sellar content
      revealed no pituitary adenoma or pituitary cells, but only an eosinophilic,
      colloid-like mass, and necrotic acellular debris. Her sister with hypopituitarism
      had an empty sella. Genetic testing in both sisters revealed the same homozygous
      c.150delA mutation in PROP1 gene. Here we report two sisters with the same PROP1
      mutation who presented in adulthood with different pituitary morphology, one of
      them with a large sellar and suprasellar mass, in which transphenoidal surgery
      provided an extremely rare opportunity for a histopathological analysis of the
      sellar content. Due to the lack of endocrine care during the transition period
      hypocortisolism which evolved, a consequence of PROP1 mutation, was not
      recognized. Empirical use of hydrocortisone in the Intensive Care in our patient
      with life-threatening acute hyponatremia was appropriate but because
      glucocorticoid therapy on its own corrects hyponatremia even after stopping
      hypertonic saline infusion, the risk for over-correction of hyponatremia in ACTH
      deficiency is high.

PMID- 21863342
TI  - The Campylobacter jejuni NCTC11168 capsule prevents excessive cytokine production
      by dendritic cells.
AB  - Campylobacter jejuni is the leading cause of human bacterial gastroenteritis
      worldwide, mainly caused by handling and consumption of contaminated poultry.
      However, the immune response to infection is poorly understood. Here, the impact
      of the C. jejuni capsule, flagella and the N-linked glycosylation system on
      cytokine production by dendritic cells was investigated. Bone marrow-derived
      murine dendritic cells (BMDCs) infected with C. jejuni lacking the N-linked
      glycosylation system produced similar amounts of cytokines compared to cells
      infected with C. jejuni 11168H wild-type (WT) cultures. C. jejuni flagellin FlaA
      mutants elicited reduced IL-6 and IL-10 production in BMDCs compared to C. jejuni
      WT and this reduction was more pronounced in TLR4(-/-) BMDCs. An acapsular C.
      jejuni mutant as well as a mutant lacking the O-methyl phosphoramidate
      modification of the capsule elicited a higher cytokine response in BMDCs.
      Experiments with TLR4(-/-) BMDCs revealed that this increased cytokine production
      was not solely dependent on signalling through TLR4. Therefore, the C. jejuni
      capsule is important to prevent excessive cytokine production by BMDCs and even
      minor changes in capsule composition such as the lack of the O-methyl
      phosphoramidate modification can lead to increased cytokine production.

PMID- 21863343
TI  - "Resources for each other." The society of German neurologists and psychiatrists
      and the Nazi "health leadership".
AB  - The history of the German Association for Psychiatry and--after its merger with
      the Society of German Neurologists in 1935--the Society of German Neurologists
      and Psychiatrists (Gesellschaft deutscher Neurologen und Psychiater, GDNP) during
      the period of National Socialism has been subjected to only rudimentary research.
      The conventionally accepted idea that two independent professional associations
      were "coordinated" from above and turned into the extended arm of Nazi genetic
      health policy (Erbgesundheitspolitik) against their will must be reconsidered.
      This paper asks how the relationship between the GDNP and the Nazi state can be
      described adequately. Psychiatry and neurology as practice and science, and the
      biopolicy development dictatorship of National Socialism functioned, so the basic
      thesis, as "resources for each other" (Mitchell Ash).

PMID- 21863344
TI  - Deficits in social cognition: a marker for psychiatric disorders?
AB  - Research on social cognition focuses on several human abilities with a huge
      diversity in the approaches to tap the different functions. Empathy, for
      instance, is a rather elaborated human ability, and several recent studies point
      to significant impairments in patients suffering from psychiatric disorders, such
      as schizophrenia or autism. Neuroimaging data from these patients commonly
      indicate neural dysfunctions accompanying the behavioral deficits. Studying the
      neural correlates of social cognition is of particular importance, because
      deficits in these domains may explain the major dysfunctions in psychiatric
      disorders that prevent effective (re) integration into work and social life. It
      has also become clearer that social cognition deficits, similar to emotion
      dysfunctions, may represent trait markers and endophenotypes of the diseases.
      However, there are several challenges for future studies on social cognitive
      dysfunctions: on the one hand, the complexity of the constructs and thus the
      variety of definitions which make it hard to develop adequate tasks. On the other
      hand, results are needed that particularly address the disorder specificity of
      these impairments, as well as their potential as endophenotypes via analyzing
      people at high-risk and their relatives.

PMID- 21863345
TI  - Treating the untreated: applying a community-based, culturally sensitive
      psychiatric intervention to confined and physically restrained mentally ill
      individuals in Bali, Indonesia.
AB  - This study identified, mapped and treated the clinical features of mentally ill
      people, who had been isolated and restrained by family and community members as a
      result of a functional failure of the traditional medical, hospital-based mental
      health model currently practiced in Indonesia. A 10-month epidemiological
      population survey was carried out in Karangasem regency of Bali, Indonesia. A
      total of 404,591 individuals were clinically interviewed, of which 895
      individuals with mental health problems were identified, with 23 satisfying
      criteria of physical restraint and confinement. Of the latter, twenty were males;
      age range was 19-69 years, all diagnosed by the researchers with schizophrenia
      spectrum disorder (ICD-10 diagnostic criteria). Duration of restraint ranged from
      3 months to 30 years (mean = 8.1 years, SD = 8.3 years). Through the application
      of a holistic intervention model, all patients exhibited a remarkable recovery
      within 19 months of treatment. We conclude that the development of a community
      based, culturally sensitive and respectful mental health model can serve as an
      optimum promoter of positive mental health outcomes.

PMID- 21863346
TI  - Is there evidence for late cognitive decline in chronic schizophrenia?
AB  - Schizophrenia (SZP) has been historically referred to as "dementia praecox"
      because of the recognition that its onset is associated with deficits in memory,
      attention and visuospatial orientation. We wondered whether there is evidence for
      additional cognitive decline late in the course of chronic SZP. This review
      examined the evidence (1) for cognitive decline late in the course of chronic
      SZP, (2) for how often the late cognitive decline occurs, and (3) whether the
      cognitive decline in late-life SZP is related to pathophysiology of SZP versus
      the superimposition of another type of dementia. A PUBMED search was performed
      combining the MESH terms schizophrenia and dementia, cognitive decline, cognitive
      impairment and cognitive deficits. A manual search of article bibliographies was
      also performed. We included longitudinal clinical studies employing standard
      tests of cognition. Cross-sectional studies and those that did not test cognition
      through standard cognitive tests were excluded. The initial search produced 3898
      studies. Employing selection criteria yielded twenty-three studies. Our data
      extraction tool included the number of patients in the study, whether a control
      group was present, the age of patients at baseline and follow-up, the study
      setting (inpatients versus outpatients), the cognitive tests employed, study
      duration, and results. Only three longitudinal studies tested for dementia using
      Diagnostic and statistical manual of mental disorder (DSM) or International
      classification of disease (ICD) criteria and compared them to controls: two
      studies demonstrated an increase in the prevalence of dementia and one did not.
      Twenty longitudinal studies tested for one or more cognitive domains without
      employing standard criteria for dementia: twelve studies demonstrated a
      heterogeneous pattern of cognitive decline and eight did not. Studies generally
      did not control for known risk factors for cognitive impairment such as
      education, vascular risk factors, apolipoprotein (ApoE) genotype and family
      history. The evidence for late cognitive decline in SZP is mixed, but, slightly
      more studies suggest that it occurs. If it occurs, it is unclear whether it is
      related to SZP or other risks for cognitive impairment. Hence, prospective,
      longitudinal, controlled studies are needed to confirm that there is progressive
      cognitive decline in chronic SZP which occurs independent of other risk factors
      for cognitive impairment.

PMID- 21863347
TI  - Characterization of seed coat post harvest darkening in common bean (Phaseolus
      vulgaris L.).
AB  - Seed coat post harvest darkening (PHD) represents a problem for producers and
      consumers of several market classes of dry bean. There are three PHD phenotypes:
      (1) non-darkening (ND), (2) slow darkening (SD) and (3) regular darkening (RD).
      The inheritance of PHD was elucidated by evaluating populations derived from
      crosses among multiple RD, SD and ND genotypes. Results indicate that at least
      two unlinked major genes control the PHD trait in common bean. Recessive
      epistasis with three phenotypic classes explains the segregation ratios of
      populations from crosses between SD and ND parents. One gene, J, is responsible
      for whether a bean will darken as seeds from plants that are jj do not darken at
      all. Another gene, sd, influences how quickly a seed coat will darken with sdsd
      individuals darkening more slowly than those with the dominant Sd allele.

PMID- 21863348
TI  - Improved phosphorus acquisition by tobacco through transgenic expression of
      mitochondrial malate dehydrogenase from Penicillium oxalicum.
AB  - Phosphorus (P) is an essential nutrient for plant growth and development, but is
      generally unavailable and inaccessible in soil, since applied P is mostly fixed
      to aluminium (Al) and ferrum (Fe) in acidic soils and to calcium (Ca) in alkaline
      soils. Increased organic acid excretion is thought to be one mechanism by which
      plants use to enhance P uptake. In this study, we overexpressed a mitochondrial
      malate dehydrogenase (MDH) gene from the mycorrhizal fungi Penicillium oxalicum
      in tobacco. The MDH activity of transgenic lines was significantly increased
      compared to that of wild type. Malate content in root exudation of transgenic
      lines induced in response to P deficiency was 1.3- to 2.9-fold greater than that
      of wild type under the same condition. Among the transgenic lines that were
      selected for analysis, one line (M1) showed the highest level of MDH activity and
      malate exudate. M1 showed a significant increase in growth over wild type, with
      149.0, 128.5, and 127.9% increases in biomass, when grown in Al-phosphate, Fe
      phosphate, and Ca-phosphate media, respectively. M1 also had better P uptake
      compared to wild type, with total P content increased by 287.3, 243.5, and 223.4%
      when grown in Al-phosphate, Fe-phosphate, and Ca-phosphate media, respectively.
      To our knowledge, this is the first study on improving the ability of a plant to
      utilize P from Al-phosphate, Fe-phosphate, and Ca-phosphate by manipulating the
      organic acid metabolism of the plant through genetic engineering.

PMID- 21863351
TI  - Dyssynchronous! Remediable?

PMID- 21863349
TI  - "But my doctor recommended pot": medical marijuana and the patient-physician
      relationship.
AB  - As the use of medical marijuana expands, it is important to consider its
      implications for the patient-physician relationship. In Colorado, a small cohort
      of physicians is recommending marijuana, with 15 physicians registering 49% of
      all medical marijuana patients and a single physician registering 10% of all
      patients. Together, they have registered more than 2% of the state to use medical
      marijuana in the last three years. We are concerned that this dramatic expansion
      is occurring in a setting rife with conflicts of interest despite insufficient
      scientific knowledge about marijuana. This system diminishes the patient
      physician relationship to the recommendation of a single substance while
      unburdening physicians of their usual responsibilities to the welfare of their
      patients.

PMID- 21863353
TI  - Blood pressure management during beach chair position shoulder surgery: what do
      we know?

PMID- 21863352
TI  - More hypotension in patients taking antihypertensives preoperatively during
      shoulder surgery in the beach chair position.
AB  - PURPOSE: Hypotension is common in patients undergoing surgery in the sitting
      position under general anesthesia, and the risk may be exacerbated by the use of
      antihypertensive drugs taken preoperatively. The purpose of this study was to
      compare hypotensive episodes in patients taking antihypertensive medications with
      normotensive patients during shoulder surgery in the beach chair position.
      METHODS: Medical records of all patients undergoing shoulder arthroscopy during a
      44-month period were reviewed retrospectively. The primary endpoint was the
      number of moderate hypotensive episodes (systolic blood pressure <= 85 mmHg)
      during the intraoperative period. Secondary endpoints included the frequency of
      vasopressor administration, total dose of vasopressors, and fluid administered.
      Values are expressed as mean (standard deviation). RESULTS: Of 384 patients who
      underwent shoulder surgery, 185 patients were taking no antihypertensive
      medication, and 199 were on at least one antihypertensive drug. The
      antihypertensive medication group had more intraoperative hypotensive episodes
      [1.7 (2.2) vs 1.2 (1.8); P = 0.01] and vasopressor administrations. Total dose of
      vasopressors and volume of fluids administered were similar between groups. The
      timing of the administration of angiotensin-converting enzyme inhibitors and of
      angiotensin receptor antagonists (<= 10 hr vs > 10 hr before surgery) had no
      impact on intraoperative hypotension. CONCLUSIONS: Preoperative use of
      antihypertensive medication was associated with an increased incidence of
      intraoperative hypotension. Compared with normotensive patients, patients taking
      antihypertensive drugs preoperatively are expected to require vasopressors more
      often to maintain normal blood pressure.

PMID- 21863354
TI  - A pilot evaluation of associations between displayed depression references on
      Facebook and self-reported depression using a clinical scale.
AB  - The objective of this study was to determine associations between displayed
      depression symptoms on Facebook and self-reported depression symptoms using a
      clinical screen. Public Facebook profiles of undergraduates from two universities
      were examined for displayed depression references. Profiles were categorized as
      depression symptom displayers or non-displayers. Participants completed an online
      PHQ-9 depression scale. Analyses examined associations between PHQ-9 score and
      depression symptom displayers versus non-displayers. The mean PHQ-9 score for non
      displayers was 4.7 (SD = 4.0), the mean PHQ-9 score for depression symptom
      displayers was 6.4 (SD = 5.1; p = 0.018). A trend approaching significance was
      noted that participants who scored into a depression category by their PHQ-9
      score were more likely to display depression symptom references. Displayed
      references to depression symptoms were associated with self-reported depression
      symptoms.

PMID- 21863355
TI  - Reproducibility of abdominal aortic aneurysm diameter measurement and growth
      evaluation on axial and multiplanar computed tomography reformations.
AB  - PURPOSE: To compare different methods measuring abdominal aortic aneurysm (AAA)
      maximal diameter (Dmax) and its progression on multidetector computed tomography
      (MDCT) scan. MATERIALS AND METHODS: Forty AAA patients with two MDCT scans
      acquired at different times (baseline and follow-up) were included. Three
      observers measured AAA diameters by seven different methods: on axial images
      (anteroposterior, transverse, maximal, and short-axis views) and on multiplanar
      reformation (MPR) images (coronal, sagittal, and orthogonal views). Diameter
      measurement and progression were compared over time for the seven methods.
      Reproducibility of measurement methods was assessed by intraclass correlation
      coefficient (ICC) and Bland-Altman analysis. RESULTS: Dmax, as measured on axial
      slices at baseline and follow-up (FU) MDCTs, was greater than that measured using
      the orthogonal method (p = 0.046 for baseline and 0.028 for FU), whereas Dmax
      measured with the orthogonal method was greater those using all other measurement
      methods (p-value range: <0.0001-0.03) but anteroposterior diameter (p = 0.18
      baseline and 0.10 FU). The greatest interobserver ICCs were obtained for the
      orthogonal and transverse methods (0.972) at baseline and for the orthogonal and
      sagittal MPR images at FU (0.973 and 0.977). Interobserver ICC of the orthogonal
      method to document AAA progression was greater (ICC = 0.833) than measurements
      taken on axial images (ICC = 0.662-0.780) and single-plane MPR images (0.772
      0.817). CONCLUSION: AAA Dmax measured on MDCT axial slices overestimates aneurysm
      size. Diameter as measured by the orthogonal method is more reproducible,
      especially to document AAA progression.

PMID- 21863356
TI  - Abstracts of CIRSE (Cardiovascular and Interventional Radiological Society of
      Europe) 2011. September 10-14, 2011. Munich, Germany.

PMID- 21863357
TI  - Neurocritical care in developing countries.
AB  - Neurocritical illness heavily burdens the developing world. In spite of a lack of
      resources for population-based health in most developing countries, there is an
      increasing demand for resource-intense strategies for acute neurological care.
      Factors including rising individual incomes in emerging economies, need for
      neurointensive care in humanitarian emergencies, growth of private hospitals, the
      rising burden of noncommunicable disease, and the practice of neurocritical care
      by specialists outside of neurology are discussed. Possible steps to improve the
      global practice of neurocritical care include: (1) emphasis on prevention of
      neurocritical illness through traffic safety and adequate outpatient treatment;
      (2) standardization of training requirements and skill sets; (3) guidelines on
      cost-effective measures including medications, equipment, and devices; (4)
      strengthening of surveillance systems and registries for both noncommunicable and
      communicable neurological diseases; (5) expanded use of teleneurology; (6)
      educational exchanges of neurointensive health care workers; and (7) monitoring
      of neurological intensive care unit death rates due to nosocomial infections,
      neurological disease, and other causes. A summary of reported mortality rates
      among neurocritically ill patients in African countries in recent years is
      provided as an illustrative example.

PMID- 21863358
TI  - Genetic diversity and differentiation in Hedychium spicatum, a valuable medicinal
      plant of Indian Himalaya.
AB  - Hedychium spicatum, a perennial rhizomatous medicinal plant distributed in
      subtropical and temperate parts, is considered nearly endemic to the Himalayan
      region.In this study allozyme markers were utilized to assess genetic variations
      and relationships among 12 distinct populations of this species from the West
      Himalaya of India. A high level of genetic diversity was found among the
      populations. Of the 13 loci generated using eight enzymes, 12 (92%) were
      polymorphic. F-statistics suggested a prevalence of a high heterozygote excess
      among populations (F(IS) = -0.51). Gene flow estimates and geographic distances
      between populations did not correlate significantly (r = -0.0258, P < 0.3550).
      The excess heterozygosity may be attributed to high pollinator mobility and
      inbreeding coefficient within the subpopulation, relative to the total F(IS)
      value. High frequencies of several alleles at different loci probably reflect the
      breeding pattern, as the species propagates clonally as well as through seeds. We
      also discuss conservation implications for the target species.

PMID- 21863359
TI  - US-guided vacuum-assisted percutaneous excision for management of benign
      papilloma without atypia diagnosed at US-guided 14-gauge core needle biopsy.
AB  - PURPOSE: To assess the diagnostic accuracy of ultrasound (US)-guided vacuum
      assisted excision (VAE) for the postbiopsy management of benign papilloma without
      atypia after US-guided 14-gauge core needle biopsy (CNB). METHODS: This was an
      institutional review board-approved retrospective study, with a waiver of
      informed consent. After a review of the histologic results and postbiopsy
      management of US-guided CNB performed from January 2007 through April 2009, 122
      benign papillomas without atypia were diagnosed at CNB and excised percutaneously
      with US-guided VAE. Among them, a total of 67 papillomas having surgical excision
      (n = 5) or at least 2 years' US follow-up (n = 62) after VAE were enrolled onto
      this study. We reviewed the medical records, US findings, and pathologic results
      obtained before and after VAE. Over the follow-up period, whether any malignancy
      at the site of the VAE was diagnosed was evaluated. RESULTS: The pathologic
      results of 67 VAEs were benign in 63 (94%) and atypical in four (6%). None of 63
      benign lesions proved to be malignant after surgical excision (n = 1) or US
      follow-up (n = 62). Of four atypical lesions, however, one was upgraded to ductal
      carcinoma-in-situ (25%) after surgical excision. Of 62 benign VAE results having
      US follow-up, 56 (90.3%) showed no residual lesion at the site of the VAE.
      CONCLUSIONS: For the postbiopsy management of benign papilloma without atypia
      after US-guided CNB, US-guided VAE was accurate and could be alternative to
      surgery. In cases of diagnosis of atypical lesion at VAE, however, surgery should
      be performed for a definitive diagnosis.

PMID- 21863360
TI  - Prognostic impact of postoperative serum CA 19-9 levels in patients with
      resectable pancreatic cancer.
AB  - BACKGROUND: Perioperative serum carbohydrate antigen 19-9 (CA 19-9) level has
      been reported to be a useful prognostic marker in pancreatic cancer. The object
      of this study was to investigate the predictive factors for survival, including
      preoperative and postoperative serum CA 19-9 levels in patients with pancreatic
      cancer. METHODS: Between 2003 and 2009, a total of 269 patients with pancreatic
      invasive ductal carcinoma underwent macroscopically curative resection, and pre-
      and postoperative (within 3 months after surgery) serum CA 19-9 levels were
      evaluated in all of them. The prognostic significance of clinicopathologic
      factors was evaluated by univariate and multivariate analyses. RESULTS:
      Preoperative serum CA 19-9 levels were higher than normal (>37 U/ml, 38-4600
      U/ml) in 218 of 269 patients. Of these, after surgery, serum CA 19-9 level
      returned to within a normal range in 136 patients (62%), whereas 82 patients
      (38%) remained in the higher-than-normal range. In univariate and multivariate
      analyses, node metastasis (P < 0.001) and postoperative CA 19-9 level (>37 U/ml)
      (P < 0.0001) were independent predictors for poor survival. Postoperative CA 19-9
      level was higher in patients with microscopically positive surgical margin (P =
      0.02). Hepatic recurrence and peritoneal dissemination were associated with
      postoperative higher CA 19-9 level. CONCLUSIONS: Postoperative CA 19-9 level was
      associated with positive surgical margin and hepatic or peritoneal recurrence and
      may be a useful predictor for survival in patients with pancreatic cancer.

PMID- 21863361
TI  - The surgical treatment of lymphedema: a systematic review of the contemporary
      literature (2004-2010).
AB  - PURPOSE: A systematic review of the literature was performed to examine
      contemporary peer-reviewed literature (2004-2010) evaluating the surgical
      treatment of lymphedema. METHODS: A comprehensive search of 11 major medical
      indices was performed. Selected articles were sorted to identify those related to
      the surgical treatment of lymphedema. Extracted data included the number of
      patients, specific surgical procedure performed, length of follow-up, criteria
      for defining lymphedema, measurement methods, volume or circumference reduction,
      and reported complications. RESULTS: A total of 20 studies met inclusion
      criteria; procedures were categorized as excisional procedures (n = 8), lymphatic
      reconstruction (n = 8), and tissue transfer (n = 4). The reported incidence of
      volume reduction of lymphedema in these studies varied from 118% reduction to a
      13% increase over the follow-up intervals ranging from 6 months to 15 years. The
      largest reported reductions were noted after excisional procedures (91.1%),
      lymphatic reconstruction (54.9%), and tissue transfer procedures (47.6%).
      Procedure complications were rarely reported. CONCLUSIONS: A number of surgical
      approaches have demonstrated beneficial effects for select patients with
      lymphedema. Most of these reports, however, are based on small numbers of
      patients, use nonstandardized or inconsistent measurement techniques, and lack
      long-term follow-up. The proposed benefits of any surgical approach should be
      evaluated in the context of the potential morbidity to the individual patient and
      the availability of surgical expertise. In addition, although these surgical
      techniques have shown promising results, nearly all note that the procedures do
      not obviate the need for continued use of conventional therapies, including
      compression, for long-term maintenance.

PMID- 21863362
TI  - Minimally invasive approach to breast cancer: is less better?

PMID- 21863363
TI  - Disparities in reconstruction rates after mastectomy for ductal carcinoma in situ
      (DCIS): patterns of care and factors associated with the use of breast
      reconstruction for DCIS compared with invasive cancer.
AB  - BACKGROUND: Many factors influence whether breast cancer patients undergo
      reconstruction after mastectomy. This study was undertaken to determine the
      patterns of care and variables associated with the use of reconstruction for
      ductal carcinoma in situ (DCIS) and to compare previous results for invasive
      carcinoma. METHODS: Postmastectomy reconstruction rates were collected from the
      California Office of Statewide Health Planning and Development (OSHPD) for 2003
      2007. International Classification of Disease-9 codes were used to identify
      patients undergoing reconstruction after mastectomy. Variations in reconstruction
      rates were examined by type of breast cancer (DCIS vs. invasive), calendar year,
      age, type of insurance, type of hospital, and race/ethnicity. Univariate and
      multivariate odds ratios (OR) with 95% confidence intervals (CI) were estimated
      for relative odds of immediate reconstruction versus mastectomy only. RESULTS:
      For multivariate analysis, age, race/ethnicity, type of insurance, and type of
      hospital were significantly associated with the use of reconstruction for DCIS
      patients. DCIS patients were twice as likely to undergo reconstruction as
      patients with invasive cancer (odds ratio (OR) = 1.93, 95% confidence interval
      (CI) = 1.75-2.13). DCIS patients with private insurance were nine times more
      likely to undergo reconstruction as patients with Medicaid (OR = 8.84, 95% CI =
      5.92-13.21). Both Hispanic white and Asian patients were one-fifth as likely to
      undergo reconstruction compared with non-Hispanic white patients (OR = 0.18, 95%
      CI = 0.1-0.3; OR = 0.17, 95% CI = 0.09-0.31). CONCLUSIONS: Postmastectomy rates
      for DCIS were twice those for invasive cancer mostly because stage was not a
      limiting factor. However, significant factors remain that limit the use of
      reconstruction in this breast cancer population: age, race/ethnicity, type of
      hospital, and type of insurance.

PMID- 21863364
TI  - Mammography in 40-year-old women: what difference does it make? The potential
      impact of the U.S. Preventative Services Task Force (USPSTF) mammography
      guidelines.
AB  - BACKGROUND: This 10-year retrospective chart review evaluates the potential
      impact the most recent U.S. Preventative Services Task Force (USPSTF) report
      recommending against annual mammographic screening of women aged 40-49 years.
      METHODS: The medical record database was systematically searched to discover all
      women aged 40-49 years treated for breast cancer over a 10-year period. These
      women were separated into 2 cohorts-mammographically detected cancer (MDC) and
      nonmammographically detected cancer (NMDC). Statistical analysis of the cohorts
      was performed for family history (FH), sentinel lymph node (SLN) status, tumor
      size at presentation, and disease-free and overall survival. RESULTS: A total of
      1581 women were treated for breast cancer; of these, 311 were between the ages of
      40 and 49 years with complete diagnostic information, 145 were MDC, and 166 were
      NMDC. The average tumor diameter of the MDC group was 20.68 mm, which was
      significantly smaller than that of the NMDC group at 30.38 mm (P < .0001). Women
      with MDC had a significantly lower incidence of SLN positive cancer than the NMDC
      group, 28 of 113 (24.78%) vs. 85 of 152 (55.92%; P < .0001), respectively. The 5
      year disease-free survival for both groups was MDC 94% (95% confidence interval
      [95% CI], 87-97%) and NMDC 71% (95% CI 62-78%). The overall 5-year survival
      estimates were MDC 97% (95% CI 92-99%) and NMDC 78% (95% CI 69-85%),
      respectively. CONCLUSION: This review demonstrates the significance of
      mammographic screening for early detection and treatment of breast cancer.
      Mammographic screening in women aged 40-49 detected smaller tumors with less
      nodal metastasis, resulting in improved survival, which supports annual
      mammographic screening in this age group.

PMID- 21863365
TI  - Can we measure the quality of breast surgical care?
AB  - Many studies have demonstrated gaps in healthcare quality for all medical and
      surgical specialties including breast surgical care. How to optimally measure and
      improve quality has generated debate at the local, state, and national level.
      Attempts to judge medical performance by private companies using non-risk
      adjusted administrative databases may not be accurate and may unfairly penalize
      surgical care. An overview of concepts to measure and improve quality of breast
      cancer care is presented with specific examples relevant to breast surgeons.
      Breast surgeons and their professional organizations need to take ownership of
      quality measure programs because others will surely do so if we do not.
      Participation in one or more of these programs is beneficial because peer
      performance comparison allows identification of potential areas for individual or
      institutional improvement and demonstrates the commitment of breast surgeons to
      quality improvement. This commitment may gain even greater importance if trends
      continue toward performance-based physician payment, patient steerage, licensure,
      and board certification.

PMID- 21863366
TI  - Metropolitan structure and neighborhood attainment: exploring intermetropolitan
      variation in racial residential segregation.
AB  - Using data from the 1981, 1991, and 2001 waves of the Panel Study of Income
      Dynamics and several decennial censuses, we examine how characteristics of
      metropolitan areas are associated with black and white households' neighborhood
      racial composition. Results from hierarchical linear models show that about 20%
      to 40% of the variation in the percentage of households' tract population that is
      non-Hispanic white or non-Hispanic black exists across metropolitan areas. Over
      time, white households' exposure to non-Hispanic white neighbors has declined,
      and their exposure to non-Hispanic black neighbors has increased; the reverse
      trends are observed for blacks. These trends cannot be attributed to changes in
      the ecological structure of metropolitan areas. Blacks have fewer white neighbors
      in large metropolitan areas containing sizable minority populations, and blacks
      have more white neighbors in metropolitan areas with high government employment.
      Whites have more black neighbors in metropolitan areas with high levels of
      government employment and ample new housing; whites have fewer black neighbors in
      metropolitan areas with a high level of municipal fragmentation. The association
      between metropolitan-area percentage black and tract percentage black is weaker
      among whites than among blacks, suggesting that whites are especially motivated
      to self-segregate in metropolitan areas with large black populations.

PMID- 21863367
TI  - Ethnic enclaves and the earnings of immigrants.
AB  - A large literature in sociology concerns the implications of immigrants'
      participation in ethnic enclaves for their economic and social well-being. The
      "enclave thesis" speculates that immigrants benefit from working in ethnic
      enclaves. Previous research concerning the effects of enclave participation on
      immigrants' economic outcomes has come to mixed conclusions as to whether enclave
      effects are positive or negative. In this article, we seek to extend and improve
      upon past work by formulating testable hypotheses based on the enclave thesis and
      testing them with data from the 2003 New Immigrant Survey (NIS), employing both
      residence-based and workplace-based measures of the ethnic enclave. We compare
      the economic outcomes of immigrants working in ethnic enclaves with those of
      immigrants working in the mainstream economy. Our research yields minimal support
      for the enclave thesis. Our results further indicate that for some immigrant
      groups, ethnic enclave participation actually has a negative effect on economic
      outcomes.

PMID- 21863368
TI  - Magnetic resonance velocity mapping of 3D cerebrospinal fluid flow dynamics in
      hydrocephalus: preliminary results.
AB  - OBJECTIVES: To investigate the detectability of CSF flow alterations in the
      ventricular system of patients with hydrocephalus using time-resolved 3D MR
      velocity mapping. METHODS: MR velocity mapping was performed in 21 consecutive
      hydrocephalus patients and 21 age-matched volunteers using a 3D phase-contrast
      (PC) sequence. Velocity vectors and particle path lines were calculated for
      visualisation of flow dynamics. CSF flow was classified as "hypomotile flow" if
      it showed attenuated dynamics and as "hypermotile flow" if it showed increased
      dynamics compared with volunteers. Diagnostic efficacy was compared with routine
      2D cine PC-MRI. RESULTS: Seven patients showed hypomotile CSF flow: six had non
      communicating hydrocephalus due to aqueductal stenosis. One showed oscillating
      flow between the lateral ventricles after craniotomy for intracranial
      haemorrhage. Seven patients showed normal flow: six had hydrocephalus ex vacuo
      due to brain atrophy. One patient who underwent ventriculostomy 10 years ago
      showed a flow path through the opening. Seven patients showed hypermotile flow:
      three had normal pressure hydrocephalus, three had dementia, and in one the
      diagnosis remained unclear. The diagnostic efficacy of velocity mapping was
      significantly higher except for that of aqueductal stenosis. CONCLUSIONS: Our
      approach may be useful for diagnosis, therapy planning, and follow-up of
      different kinds of hydrocephalus.

PMID- 21863369
TI  - The Psychosocial Distress Questionnaire-Breast Cancer (PDQ-BC) is a useful
      instrument to screen psychosocial problems.
AB  - PURPOSE: Recently, the Psychosocial Distress Questionnaire-Breast Cancer (PDQ
      BC), a screening instrument specific for patients with early-stage breast cancer,
      was developed. The aim of this study was to further examine the psychometric
      properties of the PDQ-BC, in particular the subscales social support, sexual
      problems and financial problems. METHODS: Before patients received treatment (N =
      123), they completed the PDQ-BC, the World Health Organization Quality of Life
      (WHOQOL-100) and the Center for Epidemiologic Studies Depression Scale (CES-D).
      RESULTS: Floor effects were present in 44% of the subscales, whereas ceiling
      effects were only found in the social support subscale (11%). The PDQ-BC
      subscales social support, sexual problems and financial problems were highly
      correlated with the corresponding WHOQOL-100 facets social support, sexual
      activity and financial resources. Furthermore, the subscale depressive symptoms
      (PDQ-BC) was highly significantly correlated with the CES-D. Low correlations
      were found between the PDQ-BC subscales and questionnaires that were expected to
      be unrelated. Exceptions are the subscales trait anxiety and state anxiety, which
      had a high correlation with the CES-D. The Cronbach's alpha coefficients of the
      subscales trait anxiety, state anxiety, depressive symptoms, body image and
      physical problems ranged from 0.70 to 0.87. Social problems had a low consistency
      (0.39). Corrected item-total correlations confirmed the PDQ-BC structure.
      CONCLUSIONS: The PDQ-BC has expected floor effects, few ceiling effects and
      sufficient internal consistency. Furthermore, the construct validity on the PDQ
      BC subscales social support, sexual problems and financial problems was good.
      Thus, the PDQ-BC can be used to screen psychosocial problems in patients with
      early-stage breast cancer as part of routine care.

PMID- 21863370
TI  - TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis
      induced by retrograde infusion of taurocholate.
AB  - OBJECTIVE: Neutrophil infiltration is a key regulator in the pathophysiology of
      acute pancreatitis (AP), although the impact of Toll-like receptors (TLRs) in AP
      remains elusive. The aim of this study was to define the role of TLR2 and TLR4 in
      leukocyte recruitment and tissue damage in severe AP. EXPERIMENTAL DESIGN: AP was
      induced by retrograde infusion of sodium taurocholate into the pancreatic duct in
      wild-type, TLR2- and TLR4-deficient mice. Samples were collected 24 h after
      induction of AP. RESULTS: Taurocholate challenge caused a clear-cut pancreatic
      damage characterized by increased acinar cell necrosis, neutrophil infiltration,
      focal hemorrhage and edema formation, as well as increased levels of blood
      amylase and CXCL2 (macrophage inflammatory protein-2) in the pancreas and serum.
      Moreover, challenge with taurocholate increased activation of trypsinogen in the
      pancreas. Notably, TLR2 gene-deficient mice exhibited a similar phenotype to wild
      type mice after challenge with taurocholate. In contrast, tissue damage,
      pancreatic and lung myeloperoxidase (MPO) activity, serum and pancreatic levels
      of CXCL2 as well as blood amylase were significantly reduced in TLR4-deficient
      mice exposed to taurocholate. However, taurocholate-induced activation of
      trypsinogen was intact in TLR4-deficient mice. CONCLUSION: Our data suggest a
      role for TLR4 but not TLR2 in the pathogenesis of severe AP in mice.

PMID- 21863371
TI  - Comparison of electrophysiological correlates of writing and speaking: a
      topographic ERP analysis.
AB  - Behavioral and neuropsychological studies on written production suggested that
      some cognitive processes are common with spoken production. In this study, we
      attempted to specify the time course of common processes between the two
      modalities with event-related brain potentials (ERPs). High density EEG was
      recorded on twenty two healthy participants during a handwritten and an oral
      picture naming task on the same 120 stimuli. Waveform analyses and topographical
      pattern analyses were combined on stimulus- and response-aligned ERPs in order to
      cover the whole word encoding processing. Similar electrophysiological correlates
      between writing and speaking appeared until about 260 ms. According to previous
      estimations of the time course of spoken production, the time period of identical
      electrophysiological activity corresponds to visual (0-150 ms) semantic (150-190
      ms) and lexical-semantic (190-275 ms) processes. Then, spoken and handwritten
      picture naming starts diverging and display different and modality specific
      topographical configurations from around 260 ms, i.e., at the beginning of the
      time-window associated to the encoding of the surface phonological form in spoken
      production. These results suggested shared conceptual and lexical-semantic
      processes between speaking and writing and different neurophysiological activity
      during word-form (phonological or orthographic) encoding.

PMID- 21863372
TI  - Spatiotemporal variation of karst ecosystem service values and its correlation
      with environmental factors in northwest Guangxi, China.
AB  - In this investigation we analyzed the spatiotemporal variation of ecosystem
      service values (ESVs) and its correlation with numerous environmental factors
      (EFs) for the karst region of Northwest Guangxi, China, from 1985 to 2005 using
      remote sensing, geographic information systems (GIS) and statistical techniques.
      The results indicate that historically ESVs for this karst region decreased from
      1985 (109.652 billion yuan) to 1990 (88.789 billion yuan) and then increased at
      the turn of the twenty-first century. However, the ESVs in both 2000 (103.384
      billion yuan) and 2005 (106.257 billion yuan) never achieved the level recorded
      in 1985. The total of nutrient cycling, organic production and gas regulation
      combined were 72.69, 64.57, 70.18 and 72.10% of ESVs in 1985, 1990, 2000 and
      2005, respectively. In contrast, the ESVs of water conservation, soil
      reservation, recreation and culture were determined to be relatively low
      contributing only 17.44, 23.82, 19.26 and 24.76% of total ESVs, respectively,
      during these four years. With regards to the spatial distribution of ESVs, larger
      values were recorded in the west and smaller ones recorded in the east. The most
      significant factors that were deemed to influence ESVs are annual rainfall, per
      capita cropland, slope and vegetation coverage. Annual rainfall and slope exert a
      negative force, whereas per capita cropland and vegetation coverage exert a
      positive force on ESVs. The results of the study would suggest that ecosystem
      conditions of this important karst region have been improved as the result of the
      implementation of rocky desertification control policies.

PMID- 21863373
TI  - Effects of long-term trampling on the above-ground forest vegetation and soil
      seed bank at the base of limestone cliffs.
AB  - Exposed limestone cliffs in central Europe harbor a highly divers flora with many
      rare and endangered species. During the past few decades, there has been
      increasing recreational use of these cliffs, which has caused local environmental
      disturbances. Successful restoration strategies hinge on identifying critical
      limitations. We examined the composition of aboveground forest vegetation and
      density and species composition of seeds in the soil seed bank at the base of
      four limestone cliffs in mixed deciduous forests that are intensively disturbed
      by human trampling and at four undisturbed cliffs in the Jura Mountains in
      northwestern Switzerland. We found that long-term human trampling reduced total
      aboveground vegetation cover at the base of cliffs and caused a significant shift
      in the plant-species composition. Compared with undisturbed cliffs, total seed
      density was lower in disturbed cliffs. Human trampling also altered the species
      composition of seeds in the soil seed bank. Seeds of unintentionally introduced,
      stress-tolerant, and ruderal species dominated the soil seed bank at the base of
      disturbed cliffs. Our findings indicate that a restoration of degraded cliff
      bases from the existing soil seed bank would result in a substantial change of
      the original unique plant composition. Active seed transfer, or seed flux from
      adjacent undisturbed forest areas, is essential for restoration success.

PMID- 21863374
TI  - Comparison of arterial transit times estimated using arterial spin labeling.
AB  - OBJECTIVE: To compare arterial transit time estimates from two efficient transit
      time mapping techniques using arterial spin labeling (ASL)-flow encoded arterial
      spin tagging (FEAST) and Look-Locker ASL (LL-ASL). The effects of bipolar
      gradients and label location were investigated. MATERIALS AND METHODS: Six
      healthy subjects were scanned with pseudo-continuous ASL (pCASL) FEAST and pulsed
      (PASL) and pCASL variants of LL-ASL at different labeling locations with and
      without bipolar gradients. Application of transit time mapping was demonstrated
      in a clinical case. RESULTS: Mean (+/-SD) macrovascular transit times were 363 +/
      39, 676 +/- 73 and 908 +/- 170 ms for LL-PASL, LL-pCASL with labeling offsets of
      60 and 90 mm respectively, showing linear dependence on labeling locations. Mean
      microvascular transit time for LL-pCASL was 1,463+/-135 ms, in good agreement
      with the FEAST estimate of 1,444 +/- 128 ms. Data acquired from a patient with
      stroke demonstrate how transit time and CBF maps provide complementary
      information for clinical diagnosis. CONCLUSION: Both FEAST and LL-ASL provide
      transit time information in clinically acceptable scan times. Bipolar gradients
      can be used to tailor transit time estimates for different experimental and
      clinical situations.

PMID- 21863375
TI  - Transcriptional control of natural killer cell differentiation and function.
AB  - Gene expression can be modulated depending on physiological and developmental
      requirements. A multitude of regulatory genes, which are organized in
      interdependent networks, guide development and eventually generate specific
      phenotypes. Transcription factors (TF) are a key element in the regulatory
      cascade controlling cell fate and effector functions. In this review, we discuss
      recent data on the diversity of TF that determine natural killer (NK) cell fate
      and NK cell function.

PMID- 21863376
TI  - Cis-trans interactions of cell surface receptors: biological roles and structural
      basis.
AB  - Cell surface receptors bind ligands expressed on other cells (in trans) in order
      to communicate with neighboring cells. However, an increasing number of cell
      surface receptors are found to also interact with ligands expressed on the same
      cell (in cis). These observations raise questions regarding the biological role
      of such cis interactions. Specifically, it is important to know whether cis and
      trans binding have distinct functional effects and, if so, how a single cell
      discriminates between interactions in cis versus trans. Further, what are the
      structural features that allow certain cell surface receptors to engage ligand
      both on the same as well as on an apposed cell membrane? Here, we summarize known
      examples of receptors that display cis-trans binding and discuss the emerging
      diversity of biological roles played by these unconventional two-way
      interactions, along with their structural basis.

PMID- 21863377
TI  - Is laparoscopic antireflux surgery safe and effective in obese patients?
AB  - BACKGROUND: It is not clear whether obesity has any negative impact on the
      results of laparoscopic antireflux surgery (LARS). In this prospective study we
      investigated the effect of body mass index (BMI) on the surgical outcome of LARS.
      METHODS: Patients undergoing primary LARS were divided into three groups: BMI <
      25 (normal), BMI = 25-29.9 (overweight), BMI > 30 (obese). All perioperative
      data, operative and postoperative complications, and follow-up data were recorded
      prospectively. All patients were seen 2 months postoperatively and yearly
      thereafter. RESULTS: One thousand patients underwent LARS from May 2004 to August
      2009. There were 484, 384, and 132 patients in normal, overweight, and obese
      groups, respectively. The incidence of Barrett's metaplasia (8.5% for the entire
      series) increased with BMI, although this difference was not statistically
      significant. 684 patients had Nissen and 316 had Toupet fundoplication. Mean
      follow-up was 53.33 +/- 17.21 months. There was no mortality or conversion to
      open surgery. Mean operating times were 48.04 +/- 21.20, 53.54 +/- 23.42, and
      61.33 +/- 28.47 min for normal, overweight, and obese groups, respectively (P =
      0.0001). Esophageal perforation, jejunal perforation, and pulmonary emboli were
      the three major complications in separate patients. Dysphagia occurred in 18.4,
      13.1, and 9.9% of normal, overweight, and obese patients, respectively (P =
      0.122). Bloating occurred in 18, 14.1, and 20.5 % of normal, overweight, and
      obese patients, respectively (P = 0.150). Rehospitalization for any reason,
      excluding redo surgery or dilatation, occurred less in overweight subjects (4.8,
      1, and 3.8% respectively, P = 0.008). All other minor complications were
      distributed evenly among the groups with the exception of hiccups, which occurred
      more frequently in normal weight patients. Recurrence of reflux was observed in
      0.6, 3.6, and 2.3% of the normal, overweight, and obese patients, respectively (P
      = 0.007). CONCLUSION: LARS is a safe but more demanding procedure in obese
      patients and a significant increase in complications should not be anticipated.
      Long-term control of reflux by LARS in higher-BMI patients is slightly worse than
      that in normal-weight subjects.

PMID- 21863378
TI  - Social networks of homeless youth in emerging adulthood.
AB  - Little is known about the social networks of homeless youth in emerging adulthood
      despite the importance of this information for interventions to reduce health
      risks. This study examined the composition of social networks, and the risks and
      supports present within them, in a random sample of 349 homeless youth (33.4%
      female, 23.9% African American, 17.7% Hispanic) between the ages of 18 and 24.
      Social network members who were met on the street were among the most likely to
      be perceived as engaging in risky sex, as well as to engage in substance use with
      the youth. Youth were more likely to count on relatives and sex partners for
      support compared to other network members, but they also were more likely to use
      substances with sex partners and perceived them as engaging in risky sex.
      Interventions may need to recognize the importance of intimate relationships
      during the developmental stage of emerging adulthood by enhancing supportive
      bonds and reducing substance use and risky sex in these relationships.

PMID- 21863379
TI  - A prospective study of Mexican American adolescents' academic success:
      considering family and individual factors.
AB  - Mexican American youth are at greater risk of school failure than their peers. To
      identify factors that may contribute to academic success in this population, this
      study examined the prospective relationships from 5th grade to 7th grade of
      family (i.e., human capital [a parent with at least a high school education],
      residential stability, academically and occupationally positive family role
      models, and family structure) and individual characteristics (i.e., externalizing
      symptoms, bilingualism, gender, and immigrant status) to the academic performance
      of 749 Mexican American early adolescents (average age = 10.4 years and 48.7%
      were girls in 5th grade) from economically and culturally diverse families as
      these youth made the transition to junior high school. Results indicated that
      while controlling for prior academic performance, human capital and positive
      family role models assessed when adolescents were in 5th grade positively related
      to academic performance in 7th grade. Further, being a girl also was related to
      greater 7th grade academic success, whereas externalizing symptoms were
      negatively related to 7th grade academic performance. No other variables in the
      model were significantly and prospectively related to 7th grade academic
      performance. Implications for future research and interventions are discussed.

PMID- 21863381
TI  - [Aesthetic surgery : Reconstruction of the body image to increase quality of
      life].

PMID- 21863380
TI  - Allometric scaling of pegylated liposomal anticancer drugs.
AB  - Pegylated liposomal formulations contain lipid conjugated to polyethylene glycol.
      The disposition of encapsulated drug is dictated by the composition of the
      liposome, thus altering the pharmacokinetic (PK) profile of the drug. Allometric
      scaling is based on a power-log relationship between body weight (W) and drug
      clearance (CL) among mammals and has been used to compare the disposition of
      nonliposomal drugs across species. The objectives of this study were to use
      allometric scaling to: (1) compare the disposition of pegylated liposomal drugs
      across speciesand determine the best scaling model and (2) predict PK parameters
      of pegylated liposomal drugs in humans. The PK of pegylated liposomal CKD-602 (S
      CKD602), doxorubicin (Doxil(r)), and cisplatin (SPI-077) were compared. PK
      studies ofS-CKD602, Doxil(r), and SPI-077 were performed at the maximum tolerated
      dose (MTD) in male and female mice, rats, dogs and patients with refractory solid
      tumors. The allometric equation used to evaluate the relationship between W and
      CL in each species was CL = a(W)(m) (a = empirical coefficient; m = allometric
      exponent). Substitution of physiological variables other than body weight, such
      as factors representative of the mononuclear phagocyte system (MPS) were
      evaluated. Dedrick Plots and Maximum Life-Span Potential (MLP) were used to
      determine scaling feasibility. Standard allometry demonstrated a relationship
      between clearance of S-CKD602, Doxil(r), and SPI-077 and body, spleen, liver, and
      kidney weights, total monocyte count, and spleen and liver blood flow. However,
      using scaling to predict CL of these agents in humans often resulted in
      differences >30%. Despite a strong correlation between body weight and MPS
      associated variables with CL among preclinical species, the use of the equations
      did not predict CL. Thus, new methods of allometric scaling and measures of MPS
      function need to be developed.

PMID- 21863382
TI  - [Value of fall-risk tests for patients with rheumatoid arthritis].
AB  - The aim of the study was to quickly and efficiently determine the risk of falling
      in patients with rheumatoid arthritis over the age of 46 with established
      methods, to discover parameters which influence the risk of falling and
      fractures. The study group consisted of 67 patients (median age 69+/-7.4 years,
      duration of disease <10 years 71%).With the help of the present data on fractures
      the performance of the chair-rising (CR) test, the timed up-and-go (TUG) test and
      the tandem stand (TS) test plus determination of the average daily and cumulative
      glucocorticoid (GC) dosage, it was possible to detect parameters which influence
      the risk of falling and fractures.Higher age (>60 years), overweight, deficits in
      muscle strength in the lower extremities and very low GC dosage (<=5 mg) were
      found to be associated with an increased risk of falling, which is accompanied by
      an increased risk of fractures.

PMID- 21863383
TI  - [Spondylodiscitis].
AB  - Despite highly sensitive imaging techniques, the diagnosis and treatment of
      spondylodiscitis are often delayed due to a lack of specific symptoms with back
      pain as the presenting complaint. Late diagnosis and neurological involvement at
      the time of diagnosis are risk factors for long-term neurological deficits.
      Unremitting back pain with signs of inflammation should give reason to suspect
      spondylodiscitis and to rule it out by imaging, especially if risk factors such
      as diabetes mellitus, malignant neoplasms or immunosuppression are present.
      Magnetic resonance imaging (MRI) is the imaging procedure of choice with high
      sensitivity and specificity and typically shows hypointense adjacent vertebrae on
      T1-weighted images with hyperintense signal on short tau inversion recovery
      (STIR) sequences and hyperintense disc spaces on T2-weighted images.

PMID- 21863384
TI  - [2010 Love Parade in Duisburg: clinical experiences in planning and treatment].
AB  - BACKGROUND: Tragic incidents at the 2010 Love Parade attracted significant public
      attention. As the frequency of similar events increases, more hospitals and
      practitioners will face the necessities of planning and response to unforeseeable
      occurrences. Obligatory guidelines for physicians do not exist, so that essential
      aspects are repeatedly discussed for each new event. This paper summarizes the
      experience of hospitals and emergency departments and draws conclusions, allowing
      recommendations for reasonable proposals for hospitals and practitioners. METHODS
      AND MATERIAL: A structured analysis of data concerning planning, patient flow and
      injury statistics led to a profile determining personnel, rooms and material
      which have to be provided by the hospitals. In a consensus conference afterwards
      and personal interviews with clinical coordinators the preparation of hospitals
      was evaluated to separate reasonable from needless efforts. RESULTS: We describe
      various measures concerning staff, logistics and rooms from the viewpoint of
      actual application. Reasonable measures for preparation and management of mass
      panic are analysed and described in detail. Problems are explained and solutions
      discussed. The result is a qualitative catalogue, which supports the organization
      of future events. CONCLUSION: Knowledge and reflection on the experience of the
      2010 Love Parade optimizes local emergency guidelines and planning for similar
      events. A coordinated cooperation of all involved is essential.

PMID- 21863385
TI  - Increased serum level of Nup88 protein is associated with the development of
      colorectal cancer.
AB  - Nucleoporin88 (Nup88) has been shown to be overexpressed in a wide variety of
      malignancies including colorectal cancer (CRC). However, no study about serum
      Nup88 in human CRC was reported. Therefore, in this study, we investigated the
      level of serum Nup88 protein and its relationships with clinicopathological
      variables in CRC. The serum concentration of Nup88 protein was determined by a
      quantitative sandwich enzyme-linked immunosorbent assay (ELISA) in 118 pre
      operative serum samples, 66 post-operative and 96 healthy controls. Among the
      patients, the levels of CEA (n = 91) and CA19-9 (n = 87) in the pre-operative
      serum were measured, and DNA sequencing was performed in 12 CRCs and 2 samples
      from non-cancerous colon tissue. In the same patients, the level of pre-operative
      serum Nup88 was significantly higher than that of post-operative Nup88 (P =
      0.021). Furthermore, the level of pre-operative Nup88 was positively related to
      the depth of tumor invasion (P = 0.002) and advanced stage (P = 0.001). The level
      of pre-operative Nup88 in the left colon tended to be higher than that in the
      right colon and the rectum (P = 0.063). DNA sequencing results showed that there
      were two single nucleotide polymorphisms, distributed in exon 6
      (NM_002532.3:c.1044G>A (ACG-ACA, Thr -> Thr) and exon 10 (NM_002532.3:c.1389A>T,
      CCA-CCT, Pro -> Pro). Serum Nup88 might be a candidate for a new biomarker
      implicated in the development and aggressiveness of CRCs.

PMID- 21863386
TI  - Differential assembly of polypeptides of the light-harvesting 2 complex encoded
      by distinct operons during acclimation of Rhodobacter sphaeroides to low light
      intensity.
AB  - In order to obtain an improved understanding of the assembly of the bacterial
      photosynthetic apparatus, we have conducted a proteomic analysis of pigment
      protein complexes isolated from the purple bacterium Rhodobacter sphaeroides
      undergoing acclimation to reduced incident light intensity.
      Photoheterotrophically growing cells were shifted from 1,100 to 100 W/m(2) and
      intracytoplasmic membrane (ICM) vesicles isolated over 24-h were subjected to
      clear native polyacrylamide gel electrophoresis. Bands containing the LH2 and
      reaction center (RC)-LH1 complexes were excised and subjected to in-gel trypsin
      digestion followed by liquid chromatography (LC)-mass spectroscopy (MS)/MS. The
      results revealed that the LH2 band contained distinct levels of the LH2-alpha and
      -beta polypeptides encoded by the two puc operons. Polypeptide subunits encoded
      by the puc2AB operon predominated under high light and in the early stages of
      acclimation to low light, while after 24 h, the puc1BAC components were most
      abundant. Surprisingly, the Puc2A polypeptide containing a 251 residue C-terminal
      extension not present in Puc1A, was a protein of major abundance. A predominance
      of Puc2A components in the LH2 complex formed at high light intensity is followed
      by a >2.5-fold enrichment in Puc1B levels between 3 and 24 h of acclimation,
      accompanied by a nearly twofold decrease in Puc2A levels. This indicates that the
      puc1BAC operon is under more stringent light control, thought to reflect
      differences in the puc1 upstream regulatory region. In contrast, elevated levels
      of Puc2 polypeptides were seen 48 h after the gratuitous induction of ICM
      formation at low aeration in the dark, while after 24 h of acclimation to low
      light, an absence of alterations in Puc polypeptide distributions was observed in
      the upper LH2-enriched gel band, despite an approximate twofold increase in
      overall LH2 levels. This is consistent with the origin of this band from a pool
      of LH2 laid down early in development that is distinct from subsequently
      assembled LH2-only domains, forming the LH2 gel band.

PMID- 21863387
TI  - Finger impedance evaluation by means of hand exoskeleton.
AB  - Modulation of arm mechanical impedance is a fundamental aspect for interaction
      with the external environment and its regulation is essential for stability
      preservation during manipulation. Even though past research on human arm
      movements has suggested that models of human finger impedance would benefit the
      study of neural control mechanisms and the design of novel hand prostheses,
      relatively few studies have focused on finger and hand impedance. This article
      touches on the two main aspects of this research topic: first it introduces a
      mechanical refinement of a device that can be used to effectively measure finger
      impedance during manipulation tasks; then, it describes a pilot study aimed at
      identifying the inertia of the finger and the viscous and elastic properties of
      finger muscles. The proposed wearable exoskeleton, which has been designed to
      measure finger posture and impedance modulation while leaving the palm free, is
      capable of applying fast displacements while monitoring the interaction forces
      between the human finger and the robotic links. Moreover, due to the relatively
      small inertia of the fingers, it allows us to meet some stringent specifications,
      performing relatively large displacements (~45 degrees ) before the stretch
      reflex intervenes (~25 ms). The results of measurements on five subjects show
      that inertia, damping, and stiffness can be effectively identified and that the
      parameters obtained are comparable with values from previous studies.

PMID- 21863388
TI  - [Treatment of metastatic melanoma with BRAF inhibitors].

PMID- 21863389
TI  - The effect of patient-controlled intravenous analgesia on postoperative
      hypokalemia in patients undergoing laparoscopic cholecystectomy.
AB  - PURPOSE: We investigated whether hypokalemia developed during the postoperative
      period and whether the use of intravenous patient-controlled analgesia (IV-PCA)
      could decrease the incidence of postoperative hypokalemia in patients who
      underwent laparoscopic cholecystectomy. METHODS: Sixty patients undergoing
      laparoscopic cholecystectomy were randomly assigned to either IV-PCA (n = 30) or
      control (n = 30) groups. We measured serum potassium concentration at the
      outpatient department (T1), at 8:00 a.m. on the day of surgery (T2), at 6 h after
      the end of surgery (T3), and at 8:00 a.m. on the first (T4), second (T5), and
      third (T6) postoperative days. Serum potassium concentration, incidence of
      hypokalemia, mean blood pressure, heart rate, respiratory rate, and the patient
      reported visual analogue scale score were compared within each group and between
      groups at each time point. RESULTS: Serum potassium concentrations in all
      patients showed a significant decrease at T2-T4 compared to the preoperative
      concentration (T1). Serum potassium concentrations at T3 and T4 in the IV-PCA
      group were significantly higher than those in the control group. Also, the
      incidence of hypokalemia at T3 and T4 was significantly lower in the IV-PCA
      group. Mean blood pressure and heart rate were significantly lower in the IV-PCA
      group than in controls at T3 and T4. CONCLUSIONS: The results show that
      hypokalemia developed during the perioperative period and the use of IV-PCA in
      patients undergoing laparoscopic cholecystectomy effectively decreased the degree
      and incidence of postoperative hypokalemia on the day of the operation and
      postoperative day one.

PMID- 21863390
TI  - Clinical and imaging correlates of the multiple sclerosis impact scale in
      secondary progressive multiple sclerosis.
AB  - The association of pathology and neurological deficit with quality of life (QoL)
      in multiple sclerosis (MS) is not fully understood. In this study, magnetic
      resonance imaging (MRI) measures of pathology--T1 and T2 lesion volume and ratio;
      active T2 lesion number; global and regional brain volume and atrophy;
      magnetization transfer ratio (MTR) for lesions, normal appearing grey and white
      matter (NAGM, NAWM); and spinal cord cross-sectional area-and measures of
      neurological disability (expanded disability status scale, EDSS), deficit (MS
      functional composite, MSFC) and inflammatory activity (relapse rate) were
      compared with the MS impact scale (MSIS-29), in participants in a trial of
      lamotrigine in secondary progressive MS. Data were collected from 118 people (85
      female:33 male) aged 30-61 years (mean 50.6 years)--median EDSS 6.0 (range 4.0
      7.5); mean disease duration 20.1 years (range 3-41)--at baseline and 2 years.
      Regression analysis was used to identify independently significant cross
      sectional and longitudinal correlates of the physical (MSIS-phys) and
      psychological (MSIS-psych) components of the MSIS-29; longitudinal analysis using
      the 57 people in the placebo arm. The only independently significant correlate of
      MSIS-phys was 1/timed walk (TW) (p < 0.0001, R (2) = 0.13; p = 0.047, R (2) =
      0.09); cross-sectionally the best model for MSIS-psych was the paced auditory
      serial addition test (PASAT-3) (p = 0.041) and T1-to-T2 lesion volume ratio (p =
      0.009) (R (2) = 0.13); longitudinally it was change in 1/TW (p = 0.007), mean
      NAWM MTR (p = 0.003) and NAGM peak height (p = 0.048) (R (2) = 0.32). These data
      show that MRI measures and clinical measures do impact on quality of life, but
      the association is limited.

PMID- 21863391
TI  - Is there a preferred articulating spacer technique for infected knee
      arthroplasty? A preliminary study.
AB  - BACKGROUND: Periprosthetic infection in TKA is a devastating and challenging
      problem for both patients and surgeons. Two-stage exchange arthroplasty with an
      interval antibiotic spacer reportedly has the highest infection control rate.
      Studies comparing static spacers with articulating spacers have reported varying
      ROM after reimplant, which could be due to differences in articulating spacer
      technique. QUESTIONS/PURPOSES: We therefore determined whether one of three
      articulating spacer techniques was superior in terms of (1) infection control,
      (2) final ROM, and (3) cost. PATIENTS AND METHODS: We retrospectively reviewed 53
      patients with infected TKAs who had two-stage exchange arthroplasty with one of
      three techniques with articulating spacers: autoclaving an original component (n
      = 15), a new femoral component (n = 16), and a silicone mold component (n = 22).
      We compared infection control, ROM, and cost. Minimum followup was 12 months
      (mean, 39 months; range, 12-105 months). RESULTS: We found no difference in
      infection control among the three techniques. Infection control was achieved in
      13 of 15 (86.7%) autoclaved original component spacers at mean 73 months (range,
      37-105 months), 15 of 16 (93.8%) new femoral component spacers at mean 19 months
      (range, 12-32 months), and 20 of 22 (90.9%) silicone mold component spacers at
      mean 32 months (range, 14-56 months). Mean final flexion was 95.7 degrees , 98.3
      degrees , and 93.8 degrees , respectively. Direct costs for all implants, molds,
      cement, and antibiotics were $932, $3589, and $3945, respectively. CONCLUSIONS:
      We found comparable infection control and ROM for the three techniques. Direct
      cost was least for the autoclaved original component technique.

PMID- 21863392
TI  - Repeated freeze-thaw cycles do not alter the biomechanical properties of fibular
      allograft bone.
AB  - BACKGROUND: Allograft tissues can undergo several freeze-thaw cycles between
      donor tissue recovery and final use by surgeons. However, there are currently no
      standards indicating the number of reasonable freeze-thaw cycles for allograft
      bone and it is unclear how much a graft may be degraded with multiple cycles.
      QUESTIONS/PURPOSES: We therefore asked whether (1) the mechanical properties of
      fibular allograft bone would remain unchanged with increasing numbers of freeze
      thaw cycles and (2) histologic alterations from increased numbers of freeze-thaw
      cycles would correspond to any mechanical changes. METHODS: Fibular allograft
      segments were subjected to two, four, and eight freeze-thaw cycles and compared
      biomechanically and histologically with a control group (one freeze-thaw cycle).
      Two freeze-dried treatments, one after being subjected to one freeze-thaw cycle
      and the other after being subjected to three freeze-thaw cycles, also were
      compared with the control group. RESULTS: For all segments, the average ultimate
      stress was 174 MPa, average modulus was 289 MPa, average energy was 2.00 J, and
      the average stiffness was 1320 N/mm. The material properties of the freeze-thaw
      treatment groups were similar to those of the control group: ultimate stress and
      modulus were a maximum of 16% and 70% different, respectively. Both freeze-dried
      treatments showed increased stiffness (maximum 53% +/- 71%) and energy to failure
      (maximum 117% +/- 137%) but did not exhibit morphologic differences. There were
      no alterations in the histologic appearance of the bone sections in any group.
      CONCLUSIONS: Fibular allograft segments can be refrozen safely up to eight times
      without affecting the biomechanical or morphologic properties. Freeze-dried
      treatments require further study to determine whether the detected differences
      are caused by the processing. CLINICAL RELEVANCE: Cryopreserved cortical
      allografts are thawed by surgeons in preparation for procedures and then
      occasionally discarded when not used. Refreezing allograft tissues can result in
      a cost savings because of a reduction in wasted graft material.

PMID- 21863393
TI  - A fracture does not adversely affect bone mineral density responses after
      teriparatide treatment.
AB  - BACKGROUND: Fracture leads to local and systemic catabolic physiologic changes.
      As teriparatide is an agent used to treat osteoporosis in patients with fragility
      fractures, it is unclear whether teriparatide treatment alters bone mineral
      density (BMD) and bone markers when given to patients with fractures.
      QUESTIONS/PURPOSES: We asked whether BMD and bone marker responses would be
      blunted in patients with fractures placed on teriparatide after fracture compared
      with patients without fractures on teriparatide. PATIENTS AND METHODS: We
      retrospectively collected data from 141 patients treated with teriparatide for
      osteoporosis. Seventy-seven patients received teriparatide after fractures
      (fracture group), whereas 64 were treated for other indications (nonfracture
      group). We determined BMD at the lumbar spine and at the proximal femur before
      and 12 and 24 months posttreatment. Bone markers (urine N-telopeptide [urine
      NTX], bone-specific alkaline phosphatase [BALP]) were measured at baseline and 3,
      12, and 24 months posttreatment. RESULTS: Mean lumbar spine and hip BMDs at last
      followup increased from baseline with no differences between groups to
      approximately 9% and 4% at 24 months, respectively. Both bone markers increased
      from baseline in the nonfracture group, peaking at 12 months. For the fracture
      group, only urine NTX increased at 3 and 12 months posttreatment. Although the
      peak levels of both bone markers in the nonfracture group were greater, there was
      no difference between the two groups. CONCLUSIONS: Fracture does not have a
      negative effect on the BMD and bone marker responses to teriparatide treatment.
      Clinicians should anticipate comparable BMD responses when treating patients with
      teriparatide for osteoporotic fractures and for other indications. LEVEL OF
      EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 21863395
TI  - Measuring the value of total hip and knee arthroplasty: considering costs over
      the continuum of care.
AB  - BACKGROUND: Controlling escalating costs of hip (THA) and knee arthroplasty (TKA)
      without compromising quality of care has created the need for innovative system
      reorganization to inform sustainable solutions. QUESTIONS/PURPOSES: The purpose
      of this study was to inform estimates of the value of THA and TKA by determining:
      (1) the data sources data required to obtain costs across the care continuum; (2)
      the data required for different analytical perspectives; and (3) the relative
      costs across the continuum of care. METHODS: Within the context of a pragmatic
      randomized controlled trial comparing alternative care pathways, we captured
      healthcare resource use: (1) 12 months before surgery; (2) inpatient; (3) acute
      recovery; and (4) long-term recovery 3 and 12 months postsurgery. We established
      a standardized costing model to reflect both the healthcare payer and patient
      perspectives. RESULTS: Multiple data sources from regional health authorities,
      administrative databases, and patient questionnaire were required to estimate
      costs across the care continuum. Inpatient and acute care costs were
      approximately 60% of the total with the remaining 40% incurred 12 months
      presurgery and 12 months postsurgery. Regional health authorities bear close to
      60%, and patient costs are approximately 30% of the mean total costs, most of
      which were incurred after the acute inpatient stay. CONCLUSIONS: To fully
      understand the value of an orthopaedic intervention such as THA and TKA, a
      broader perspective than one limited to the payer should be considered using a
      standardized measurement framework over a relevant time horizon and from multiple
      viewpoints to reflect the substantial patient burden and support sustainable
      improvement over the care continuum. LEVEL OF EVIDENCE: Level III, economic and
      decision analyses study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21863394
TI  - Case reports: the influence of selective voluntary motor control on gait after
      hamstring lengthening surgery.
AB  - BACKGROUND: Preliminary evidence suggests selective voluntary motor control
      (SVMC), defined as performance of isolated voluntary joint movement on request,
      may be an important factor affecting functional movement tasks. Individuals with
      poor SVMC are unable to dissociate hip and knee synergistic movement during the
      swing phase of gait and have difficulty extending their knee while the hip is
      flexing during terminal swing regardless of hamstring length. This pattern may
      limit their ability to take advantage of hamstring-lengthening surgery (HLS) and
      may explain a lack of improved stride length postoperatively. QUESTIONS/PURPOSES:
      Provide a preliminary clinical and conceptual framework for using SVMC to predict
      swing phase parameters of gait after HLS. PATIENTS AND METHODS: We contrasted two
      patients with spastic diplegia of similar age, gross motor function, and
      spasticity but with different SVMC scores using the Selective Control Assessment
      of the Lower Extremity (SCALE). The patients underwent bilateral HLS. Popliteal
      angles, joint kinematics, step length, stride length, and walking velocity were
      assessed pre- and postoperatively. RESULT: Popliteal angles, terminal knee
      extension, and knee range of motion improved for both patients. However, only the
      patient with higher SCALE scores improved stride length postoperatively.
      CONCLUSION: Although preliminary, the data suggest that SVMC, as measured by
      SCALE, may be a prognostic factor for improved stride length after HLS in
      patients with spastic diplegia. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 21863396
TI  - Functional restoration of critically sized segmental defects with bone
      morphogenetic protein-2 and heparin treatment.
AB  - BACKGROUND: Bone defects and fracture nonunions remain a substantial challenge
      for clinicians. Grafting procedures are limited by insufficient volume and donor
      site morbidity. As an alternative, biomaterial scaffolds functionalized through
      incorporation of growth factors such as bone morphogenetic proteins (BMPs) have
      been developed and appear to regenerate the structure and function of damaged or
      degenerated skeletal tissue. OBJECTIVES/PURPOSES: Our objectives were therefore
      to determine whether: (1) the addition of heparin alone to collagen scaffolds
      sufficed to promote bone formation in vivo; (2) collagen-heparin scaffold
      improved BMP-mediated bone regeneration; and (3) precomplexed heparin and BMP-2
      delivered on collagen scaffold could restore long bone biomechanical strength.
      METHODS: We created bilateral surgical defects in the femora of 20 rats and
      filled the defects with PCL scaffolds with one of five treatments: collagen
      matrix (n = 5), collagen/heparin matrix (n = 7), collagen matrix + BMP-2 (n = 9),
      collagen/heparin matrix + BMP-2 (n = 9), or collagen matrix + BMP-2/heparin
      complex (n = 9). Bone formation was observed with radiographs and micro-CT
      analysis and biomechanical testing was used to assess strength. RESULTS: The
      addition of heparin alone to collagen did not promote bone ingrowth and the
      addition of heparin to collagen did not improve BMP-mediated bone regeneration.
      Delivery of precomplexed BMP-2 and heparin in a collagen matrix resulted in new
      bone formation with mechanical properties similar to those of intact bone.
      CLINICAL RELEVANCE: Our findings suggest delivery of precomplexed BMP-2 and
      heparin may be an advantageous strategy for treatment of clinically challenging
      bone defects.

PMID- 21863398
TI  - Tungiasis in a free-ranging jaguar (Panthera onca) population in Brazil.
AB  - Tungiasis is an ectoparasitic disease caused by fleas of the genus Tunga. The
      disease is reported to occur mostly in human populations. In wildlife, however,
      the occurrence and impact of this disease remains uncertain. We captured and
      examined 12 free-ranging jaguars for the presence of Tunga penetrans in the
      Pantanal region of Mato Grosso do Sul state, Brazil. Tungiasis prevalence was
      100% in the population; lesions were confined to the jaguar's paws. T. penetrans
      was identified based on the characteristics of the embedded fleas and the
      morphological identification of a collected free-living flea. The intensity and
      stage of infestation varied between individual animals. However, in general, all
      captured jaguars were in good health. The 100% prevalence of tungiasis may be
      related to the fact that all captures were performed during the dry season. Their
      high ecological requirements for space make jaguars potential disseminators of T.
      penetrans in the Pantanal region. Because cattle ranching and ecotourism are the
      main economic activities in the Pantanal, further studies should evaluate the
      risks of tungiasis to human and animal health. To the best of our knowledge, this
      is the first report of tungiasis in jaguars.

PMID- 21863397
TI  - The Otto Aufranc Award: Demineralized bone matrix around porous implants promotes
      rapid gap healing and bone ingrowth.
AB  - BACKGROUND: Noncemented revision arthroplasty is often complicated by the
      presence of bone implant gaps that reduce initial stability and biologic
      fixation. Demineralized bone matrix has osteoinductive properties and therefore
      the potential to enhance gap healing and porous implant fixation.
      QUESTIONS/PURPOSES: We determined at what times and to what extent demineralized
      bone matrix promotes gap healing and bone ingrowth around a porous implant.
      METHODS: We inserted porous titanium implants into the proximal metaphyses of
      canine femora and humeri, with an initial 3-mm gap between host cancellous bone
      and implants. We left the gaps empty (control; n = 12) or filled them with either
      demineralized bone matrix (n = 6) or devitalized demineralized bone matrix
      (negative control; n = 6) and left them in situ for 4 or 12 weeks. We quantified
      volume healing of the gap with new bone using three-dimensional micro-CT scanning
      and quantified apposition and ingrowth using backscattered scanning electron
      microscopy. RESULTS: The density of bone inside gaps filled with demineralized
      bone matrix reached 64% and 93% of surrounding bone density by 4 and 12 weeks,
      respectively. Compared with empty controls and negative controls at 4 and 12
      weeks, gap healing using demineralized bone matrix was two to three times greater
      and bone ingrowth and apposition were up to 15 times greater. CONCLUSIONS:
      Demineralized bone matrix promotes rapid bone ingrowth and gap healing around
      porous implants. CLINICAL RELEVANCE: Demineralized bone matrix has potential for
      enhancing implant fixation in revision arthroplasty.

PMID- 21863399
TI  - Ultrastructure and molecular phylogenetics of Helmichia lacustris, a
      microsporidium with an uncoiled isofilar polar filament.
AB  - The description of Helmichia lacustris Voronin (Parazitologiya 34:327-331 1998)
      is supplemented with morphogenesis and ultrastructure of the extrusion apparatus.
      Formation of the anterior (made up by rare short lamellae) and posterior (made up
      by spongy matter or small vesicles) regions of the polaroplast is preceded by
      granulated spheres and agglomerations of bean-like bodies, respectively. The
      anchoring disc is formed by an oval structure of moderate electron density,
      sometimes possessing a granular texture. The parasite development occurs within
      the cisterns of granular endoplasmatic reticulum (ER) of the host cell. Each
      group of spores is enclosed within a two-layered sheath, including the smooth
      inner membrane of the sporophorous vesicle and the outer ribosome-encrusted
      membrane (which originates from the host cell ER) of the parasitophorous vacuole.
      Two microsporidia, H. lacustris (GenBank accession number GU130406) and
      Euplotespora binucleata (GenBank accession number DQ675604) share 78.1% of 16S
      rRNA gene sequence similarity. Both parasites are characterized by an uncoiled
      isofilar polar filament. They form a cluster nested among terrestrial and aquatic
      microsporidia with well-developed coiled polar filaments, suggesting that an
      uncoiled polar filament in this species is a result of reduction, rather than a
      "primitive" character.

PMID- 21863400
TI  - A prospective study of influenza vaccination and a comparison of immunologic
      parameters in children and adults with chromosome 22q11.2 deletion syndrome
      (digeorge syndrome/velocardiofacial syndrome).
AB  - Prior to the advent of cardiac bypass, most children with congenital cardiac
      anomalies and chromosome 22q11.2 deletion syndrome died. With improved
      technology, there is now a wave of young adults with chromosome 22q11.2 deletion
      syndrome requiring clinical care. Fifteen young children and 20 adults with
      chromosome 22q11.2 deletion had flow cytometry, functional T cell analyses, and
      functional B cell analyses to characterize their immune system. Subjects were
      vaccinated with the annual inactivated influenza vaccine, and responses were
      evaluated by hemagglutination inhibition titer assessment. The pattern of T cell
      subset abnormalities was markedly different between pediatric and adult patients.
      In spite of the cellular deficits observed in adults, titers produced after
      influenza vaccine administration were largely intact. We conclude that disruption
      to T cell production appears to have secondary consequences for T cell
      differentiation and B cell function although the clinical impact remains to be
      determined.

PMID- 21863402
TI  - Cystic fibrosis carrier screening in Veneto (Italy): an ethical analysis.
AB  - A recent study by Castellani et al. (JAMA 302(23):2573-2579, 2009) describes the
      population-level effects of the choices of individuals who underwent molecular
      carrier screening for cystic fibrosis (CF) in Veneto, in the northeastern part of
      Italy, between 1993 and 2007. We discuss some of the ethical issues raised by the
      policies and individual choices that are the subject of this study. In
      particular, (1) we discuss the ethical issues raised by the acquisition of
      genetic information through antenatal carrier testing; (2) we consider whether by
      choosing to procreate naturally these couples can harm the resulting child and/or
      other members of society, and what the moral implications of such harm would be;
      (3) we consider whether by choosing to avoid natural procreation carrier couples
      can harm current or future individuals affected by cystic fibrosis; (4) we
      discuss whether programs that make carrier testing available can be considered
      eugenic programs.

PMID- 21863401
TI  - Pediatric infratentorial ependymoma: prognostic significance of anaplastic
      histology.
AB  - Pediatric infratentorial ependymomas are difficult to cure. Despite the
      availability of advanced therapeutic modalities for brain tumors, total surgical
      resection remains the most important prognostic factor. Recently, histological
      grade emerged as an independent prognostic factor for intracranial ependymoma. We
      retrospectively reviewed the treatment outcome of 33 pediatric patients with
      infratentorial ependymoma. Progression-free survival (PFS) and overall survival
      (OS) rates were calculated and relevant prognostic factors were analyzed.
      Fourteen patients (42%) were under the age of 3 at diagnosis. Gross total
      resection was achieved in 16 patients (49%). Anaplastic histology was found in 13
      patients (39%). Adjuvant therapies were delayed until progression in 12 patients
      (36%). Actuarial PFS rates were 64% in the first year and 29% in the fifth year.
      Actuarial OS rates were 91% in the first year and 71% in the fifth year. On
      univariate analysis, brainstem invasion (P = 0.047), anaplastic histology (P =
      0.004), higher mitotic count (P = 0.001), and higher Ki-67 index (P = 0.004) were
      significantly related to a shorter PFS. Gross total resection (P = 0.029) and a
      greater age at diagnosis (P = 0.033) were significantly related to a longer PFS.
      On multivariate analysis, anaplastic histology alone was significantly related to
      a shorter PFS (P = 0.023). Gross total resection (P = 0.039) was significantly
      related to a longer overall survival (OS) on multivariate analysis. Anaplastic
      histology and gross total resection were the most important clinical factors
      affecting PFS and OS, respectively. Anaplastic histology, mitotic count, and Ki
      67 index can be used as universal and easily available prognostic parameters in
      infratentorial ependymomas.

PMID- 21863404
TI  - [Selection procedure of scientific contributions for the German Society for
      Urology (DGU) Congress 2011].

PMID- 21863403
TI  - Standardized flavonoid-rich Eugenia jambolana seed extract retards in vitro and
      in vivo LDL oxidation and expression of VCAM-1 and P-selectin in atherogenic
      rats.
AB  - The present inventory evaluates anti-atherogenic potential of flavonoid-rich
      Eugenia jambolana seed extract (EJSE) against in vitro low-density lipoprotein
      (LDL) oxidation, foam cell formation, and atherogenic (ATH) diet-induced
      experimental atherosclerosis in rats. EJSE was able to prevent in vitro LDL
      oxidation and oxidized LDL-induced macrophage foam cell formation. Also, EJSE
      supplementation to ATH rats significantly minimized increment in serum markers of
      LDL oxidation. The ex vivo oxidation indices were also minimized in LDL of EJSE
      treated animals. Microscopic evaluation of thoracic aorta of ATH + EJSE rats
      recorded minimal evidence of atheromatous plaque formation, accumulation of lipid
      laden macrophages, calcium deposition, and expression of cell adhesion molecules
      (vascular cell adhesion molecule-1 and P-selectin). This is the first scientific
      report that demonstrates anti-atherogenic potential of EJSE and warrants further
      evaluation at clinical level.

PMID- 21863406
TI  - [Position paper on urological oncology].

PMID- 21863407
TI  - [Position paper on urological oncology. Joint statement of the German Society for
      Urology, the Professional Association of German Urologists and the Working Group
      Urological Oncology of the German Cancer Society].

PMID- 21863408
TI  - [Current developments in the diagnostics and therapy of bladder carcinoma].
AB  - Considerable progress has been made in nearly all clinical scenarios of bladder
      carcinoma. Nevertheless early detection of bladder carcinoma using urine markers
      is still difficult so that none of the available tests can be recommended as a
      screening test. Photodynamic diagnostics and resection has now been shown for the
      first time to improve recurrence-free survival of patients but this impact on
      survival has to be confirmed in a phase III clinical trial before being regarded
      as standard of care. In pT1G3 tumors early cystectomy seems to improve the
      prognosis compared to organ preserving strategies. The value of adjuvant
      chemotherapy is becoming more and more evident, as, apart from several
      retrospective analyses it has been shown to improve survival in a clinical phase
      III trial. Furthermore, molecular markers are gaining importance and in the
      future can be used for identifying patients who may benefit from systemic
      chemotherapy of bladder carcinoma.

PMID- 21863409
TI  - [News from andrology. Infertility, erectile dysfunction, and hypogonadism].
AB  - This contribution discusses new aspects in andrology focusing on infertility,
      erectile dysfunction (ED), and hypogonadism. Topics such as prostatitis and
      detection of Chlamydia, idiopathic infertility and PDE5 inhibitors, and ED after
      GreenLight laser treatment are addressed.

PMID- 21863410
TI  - [Operative treatment of renal cell carcinoma].
AB  - Renal cell carcinoma represents the fifth most frequent malignant tumor in
      humans. At the time of diagnosis, 20% of the patients already manifest
      metastases. A further 20-30% of the patients develop systemic metastases in the
      postoperative course. Despite continued advances in pharmacological treatment
      options, cancer surgery tailored to the individual tumor findings constitutes the
      only curative treatment option.

PMID- 21863420
TI  - Imaging in Parkinsonism and other extrapyramidal disorders.

PMID- 21863419
TI  - Atrophy: When too much atrophy is too little brain.

PMID- 21863421
TI  - Imaging Alzheimer in 2011.

PMID- 21863423
TI  - Annular tears, fissures or HIZ?

PMID- 21863422
TI  - Other dementias.

PMID- 21863424
TI  - Degenerative facet joint disease.

PMID- 21863425
TI  - Hyperintense vertebral lesions.

PMID- 21863426
TI  - "Spinal degeneration: beyond degenerative disc disease": how to discriminate
      degeneration from spondylarthropathies?

PMID- 21863427
TI  - The normal aging spine and degenerative spinal disease.

PMID- 21863428
TI  - Osteoporosis.

PMID- 21863429
TI  - The "dehydrated" lumbar intervertebral disk on MR, its anatomy, biochemistry and
      biomechanics.

PMID- 21863430
TI  - New techniques in spinal imaging.

PMID- 21863431
TI  - Minimal invasive treatment of vertebral compression fractures: vertebroplasty.

PMID- 21863432
TI  - Kyphoplasty.

PMID- 21863433
TI  - Ozone therapy.

PMID- 21863435
TI  - One- and two-dimensional blue native-PAGE and immunodetection of low-abundance
      chloroplast membrane protein complexes.
AB  - Blue native polyacrylamide gel electrophoresis (BN-PAGE) is a powerful method for
      separating protein complexes from biological membranes under native conditions.
      BN-PAGE provides much higher resolution than gel filtration or sucrose density
      gradient centrifugation, and it can be used to estimate the molecular mass of
      protein complexes. First, membrane protein complexes need to be solubilized with
      a mild nonionic detergent such as digitonin or dodecyl maltoside. Coomassie
      brilliant blue G-250, a negatively charged dye that binds to the surface of the
      solubilized complexes, is then added so these can be resolved according to their
      size by non-denaturing (native) electrophoresis. BN-PAGE can be combined with a
      second dimension SDS-PAGE step (two-dimensional (2D)-BN/SDS-PAGE), so that the
      subunits making up these complexes are also separated according to their size.
      Here, we present our 2D-BN/SDS-PAGE method, and subsequent immunoblotting method,
      for the detection of relatively low-abundance proteins from plant chloroplasts.

PMID- 21863436
TI  - Analysis of thylakoid protein complexes by two-dimensional electrophoretic
      systems.
AB  - Photosynthetic machinery in the thylakoid membrane is prone to modifications
      depending on -environmental, developmental, and morphological parameters. Such
      plasticity in the composition of the thylakoid membrane protein complexes
      guarantees efficient function of the photosynthetic machinery. In this chapter,
      we describe methods for separation of thylakoid membrane protein complexes at
      high resolution by two-dimensional gel electrophoretic systems. Solubilization of
      the thylakoid membrane protein complexes either by dodecylmaltoside or digitonin
      is described first. Then, two partially overlapping -methods, blue native gel
      electrophoresis and high-resolution clear native gel electrophoresis, are
      demonstrated to separate the individual protein complexes. Finally, denaturing
      SDS-polyacrylamide gel electrophoresis is used to reveal the protein composition
      of each complex. Critical points in all protocols are addressed and
      representative examples of the composition of Arabidopsis thaliana thylakoid
      membrane protein complexes are shown.

PMID- 21863437
TI  - Preparation of multiprotein complexes from Arabidopsis chloroplasts using tandem
      affinity purification.
AB  - Since its first description in 1998 (Rigaut et al., Nat Biotech 17:1030-1032,
      1999), the TAP method, for Tandem Affinity Purification, has become one of the
      most popular methods for the purification of in vivo protein complexes and the
      identification of their composition by subsequent mass spectrometry analysis. The
      TAP method is based on the use of a tripartite tag fused to a target protein
      expressed in the organism of interest. A TAP tag has two independent binding
      regions separated by a protease cleavage site, and therefore allows two
      successive affinity purification steps. The most common TAP tag consists of two
      IgG binding repeats of Protein A from Staphylococcus aureus (ProtA) separated
      from a calmodulin-binding peptide by a Tobacco Etch Virus (TEV) protease cleavage
      site. Using the TAP method, native protein complexes can be purified efficiently
      with a reduced contaminant background when compared to single step purification
      methods. Initially developed in the yeast model system, the TAP method has been
      adapted to most common model organisms. The first report of the purification of
      protein complexes from plant tissue by the TAP method was published in 2004 by
      Rohila et al. (Plant J 38:172-181, 2004). The synthetic TAP tag gene described in
      this study has been optimized for use in plants, and since then, has been
      successfully used from single gene analyses to high-throughput studies of whole
      protein families (Rohila et al., PLoS ONE 4:e6685, 2009). Here, we describe a TAP
      tag purification method for the purification of protein complexes from total
      Arabidopsis extracts, that we employed successfully using a TAP-tagged
      chloroplast outer envelope protein.

PMID- 21863438
TI  - Studying interactions between chloroplast proteins in intact plant cells using
      bimolecular fluorescence complementation and Forster resonance energy transfer.
AB  - Protein-protein interactions play crucial roles in the execution of many cellular
      functions, including those in plastids. Identifying and characterising protein
      protein interactions can yield valuable information regarding the function of a
      protein and can also contribute towards understanding protein-protein interaction
      networks in plastids, thereby contributing to a better understanding of cellular
      processes. Here, we describe the planning and experimental procedures required to
      perform both bimolecular fluorescence complementation and Forster resonance
      energy transfer assays to detect protein-protein interactions. Arabidopsis is
      well-suited for microscopy and its small size facilitates live cell imaging,
      enabling observation of protein-protein interactions in living chloroplasts. The
      methods described in this chapter can be used to analyse protein-protein
      interactions of two known proteins and to dissect interacting protein domains.

PMID- 21863439
TI  - Studying chloroplast protein interactions in vitro: an overview of the available
      methods.
AB  - The analysis of protein-protein interactions is essential for the understanding
      of the molecular events in enzymatic pathways, signaling cascades, or transport
      processes in the chloroplast. A large variety of methods are available, which
      range from qualitative assays allowing for screening for new interaction
      partners, and semiquantitative assays allowing for a rough description of the
      interaction between two partners, to quantitative assays that permit detailed
      determination of kinetic and thermodynamic parameters. We summarize the available
      technologies, describe their range of applications and pitfalls, and give some
      examples from chloroplast research. The described techniques are generic and
      thereby important and useful to study the interaction network of proteins in
      Arabidopsis thaliana. In addition, we refer the reader to detailed protocols
      published elsewhere for each method.

PMID- 21863440
TI  - Proteome databases and other online resources for chloroplast research in
      Arabidopsis.
AB  - Proteomics aimed at addressing sub cellular fractions, such as chloroplasts, are
      a complex challenge. In the past few years, several studies in different
      laboratories have identified and, more recently, quantified, thousands of
      proteins within whole chloroplasts or chloroplast fractions. A considerable
      number of these studies are available for querying, using online resources, such
      as databases containing the proteins identified, encoding genes, acquired
      spectra, and phosphopeptides. The main purpose of this review is to identity and
      highlight useful features of these online resourses, mainly focused in proteomics
      databases related to chloroplast research in Arabidopsis thaliana. Several web
      sites were consulted. Among them, 11 were selected and discussed herein. The
      databases were classified into Plastid Databases, General Organelle Proteome
      Databases, and General Arabidopsis Proteome Databases. Special care was taken to
      present information regarding protein identification, protein quantification, and
      data integration. A selected list of online resources is presented in two tables.
      The databases analyzed are a useful source of information for researchers in the
      plastid organelle and plant proteomics fields.

PMID- 21863441
TI  - Use of transcriptomics to analyze chloroplast processes in Arabidopsis.
AB  - The vast majority of the several thousands of chloroplast proteins are encoded by
      nuclear genes. Regulation of their expression involves control of their
      transcription, and thus requires the transmission of information from chloroplast
      to nucleus (retrograde signalling). The most powerful approach to the analysis of
      the transcriptional regulation of chloroplast functions involves RNA
      hybridization to microarrays representing almost all nuclear genes of Arabidopsis
      thaliana, followed by statistical data analysis. This chapter provides detailed
      protocols for the preparation of RNA for microarray experiments, in particular
      the widely used Affymetrix ATH1 array. Finally, the use of the publicly available
      program Robin for statistical data analysis, as well as approaches to confirm
      microarray data, is introduced.

PMID- 21863442
TI  - Use of non-aqueous fractionation and metabolomics to study chloroplast function
      in Arabidopsis.
AB  - Chloroplasts are the chemical factories of plant cells because they are able to
      fix inorganic carbon and -convert it to a wide-range of photoassimilates that are
      exported to the cytosol and other sub-cellular compartments. If the regulation of
      these processes is to be understood, the in vivo concentrations of a large number
      of metabolites have to be measured in all of these compartments separately.
      Sophisticated analytical approaches and continued advances in the technology of
      mass spectrometry coupled to a variety of fractionation and separation techniques
      allow the reliable analysis of a comprehensive complement of metabolites in
      photosynthetic tissues. Metabolomic approaches allow the multi-parallel analysis
      of a wide-range of metabolic intermediates and have been used for rapid
      phenotyping of different genotypes and environmental effects in plants. In
      addition to this, methods have been developed to analyse metabolite levels in
      different sub-cellular compartments of plant cells. Here, we describe methods for
      sub-cellular fractionation of Arabidopsis leaves using a non-aqueous density
      gradient technique, sample preparation suitable for metabolite profiling using
      gas-chromatography-mass spectrometry, and calculation of sub-cellular metabolite
      concentrations.

PMID- 21863443
TI  - Chloroplast phenomics: systematic phenotypic screening of chloroplast protein
      mutants in Arabidopsis.
AB  - As part of a project to analyze chloroplast functional networks systematically,
      we have subjected mutants in >3,200 nuclear genes predicted to encode chloroplast
      targeted proteins in Arabidopsis thaliana (http://www.plastid.msu.edu) to
      parallel phenotypic assays. Detailed methods are presented for the various assays
      being used in this project to study chloroplast biology. These include
      morphological analysis of plants, chloroplasts, and seeds using controlled
      vocabulary. Metabolites synthesized in the chloroplast such as starch, amino
      acids, and fatty acids are analyzed in groups according to their chemical
      properties. As an indicator for the relative composition of seed storage oil and
      proteins, the carbon and nitrogen contents are determined by an elemental
      analyzer. The methods in this chapter describe how the assays are configured to
      run in relatively high throughput, maximizing data quality.

PMID- 21863444
TI  - Preparation of envelope membrane fractions from Arabidopsis chloroplasts for
      proteomic analysis and other studies.
AB  - Plastids are semiautonomous organelles restricted to plants and protists. These
      plastids are surrounded by a double membrane system, or envelope. These envelope
      membranes contain machineries to import nuclear-encoded proteins, and
      transporters for ions or metabolites, but are also essential for a range of
      plastid-specific metabolisms. Targeted semiquantitative proteomic investigations
      have revealed specific cross-contaminations by other cell or plastid compartments
      that may occur during chloroplast envelope purification. This article describes
      procedures developed to recover highly purified envelope fractions starting from
      Percoll-purified Arabidopsis chloroplasts, gives an overview of possible cross
      contaminations, provides some tricks to limit these cross-contaminations, and
      lists immunological markers and methods that can be used to assess the purity of
      the envelope fractions.

PMID- 21863445
TI  - Preparation of stroma, thylakoid membrane, and lumen fractions from Arabidopsis
      thaliana chloroplasts for proteomic analysis.
AB  - For many studies regarding important chloroplast processes such as oxygenic
      photosynthesis, fractionation of the total chloroplast proteome is a necessary
      first step. Here, we describe a method for isolating the stromal, the thylakoid
      membrane, and the thylakoid lumen subchloroplast fractions from Arabidopsis
      thaliana leaf material. All three fractions can be isolated sequentially from the
      same plant material in a single day preparation. The isolated fractions are
      suitable for various proteomic analyses such as simple mapping studies or for
      more complex experiments such as differential expression analysis using two
      dimensional difference gel electrophoresis (2D-DIGE) or mass spectrometry (MS)
      based techniques. Besides this, the obtained fractions can also be used for many
      other purposes such as immunological assays, enzymatic activity assays, and
      studies of protein complexes by native-polyacrylamide gel electrophoresis (native
      PAGE).

PMID- 21863446
TI  - Preparation of plastoglobules from Arabidopsis plastids for proteomic analysis
      and other studies.
AB  - Plastoglobules are particles specifically located inside different types of
      plastids. They mainly contain lipids and proteins and are physically attached to
      thylakoids. Proteomic studies have underlined the role of plastoglobules in
      diverse plastid metabolic pathways, such as those producing vitamin K, vitamin E,
      and carotenoids, and have implicated them in plant response to stress. This
      chapter describes the isolation of pure and intact plastoglobules from
      Arabidopsis leaves. The procedure starts with the isolation of intact
      chloroplasts by centrifugation on a Percoll gradient. Plastoglobules are then
      separated from the plastid membranes by flotation on a sucrose gradient. Finally,
      the purity of the plastoglobule fraction is verified by immunoblotting.

PMID- 21863447
TI  - Preparation and proteomic analysis of chloroplast ribosomes.
AB  - Proteomics of chloroplast ribosomes in spinach and Chlamydomonas revealed unique
      protein composition and structures of plastid ribosomes. These studies have
      suggested the presence of some ribosomal proteins unique to plastid ribosomes
      which may be involved in plastid-unique translation regulation. Considering the
      strong background of genetic analysis and molecular biology in Arabidopsis, the
      in-depth proteomic characterization of Arabidopsis plastid ribosomes would
      facilitate further understanding of plastid translation in higher plants. Here, I
      describe simple and rapid methods for the preparation of plastid ribosomes from
      Chlamydomonas and Arabidopsis using sucrose gradients. I also describe purity
      criteria and methods for yield estimation of the purified plastid ribosomes and
      subunits, methods for the preparation of plastid ribosomal proteins, as well as
      the identification of some Arabidopsis plastid ribosomal proteins by matrix
      assisted laser desorption/ionization mass spectrometry.

PMID- 21863448
TI  - The workflow for quantitative proteome analysis of chloroplast development and
      differentiation, chloroplast mutants, and protein interactions by spectral
      counting.
AB  - This chapter outlines a quantitative proteomics workflow using a label-free
      spectral counting technique. The workflow has been tested on different aspects of
      chloroplast biology in maize and Arabidopsis, including chloroplast mutant
      analysis, cell-type specific chloroplast differentiation, and the proplastid-to
      chloroplast transition. The workflow involves one-dimensional SDS-PAGE of the
      proteomes of leaves or chloroplast subfractions, tryptic digestions, online LC
      MS/MS using a mass spectrometer with high mass accuracy and duty cycle, followed
      by semiautomatic data processing. The bioinformatics analysis can effectively
      select best gene models and deals with quantification of closely related
      proteins; the workflow avoids overidentification of proteins and results in more
      accurate protein quantification. The final output includes pairwise comparative
      quantitative analysis, as well as hierarchical clustering for discovery of
      temporal and spatial patterns of protein accumulation. A brief discussion about
      potential pitfalls, as well as the advantages and disadvantages of spectral
      counting, is provided.

PMID- 21863449
TI  - Use of phosphoproteomics to study posttranslational protein modifications in
      Arabidopsis chloroplasts.
AB  - The posttranslational modification of proteins is important for the regulation of
      enzymatic activity, protein half-life, and interaction with other molecules. One
      of the best understood posttranslational modifications is the reversible
      phosphorylation of proteins at serine, threonine, or tyrosine residues. These
      phosphoamino acids are relatively stable in acidic solutions, and their
      comprehensive identification by mass spectrometry is, therefore, feasible.
      Phosphoproteomics-type experiments require some modifications in the sample
      preparation, mass spectrometry setup, and software-based data interpretation
      compared to standard proteomics workflows. Furthermore, phosphoproteome analyses
      are incompatible with long organelle isolation procedures prior to analysis,
      because of the highly dynamic nature of regulatory phosphorylations. In this
      chapter, we provide a detailed step-by-step overview of the complex experimental
      setup required for successful chloroplast phosphoproteome analysis, report our
      experience with existing methods, and comment on their application in the field.

PMID- 21863450
TI  - Use of a pulse-amplitude modulated chlorophyll fluorometer to study the
      efficiency of photosynthesis in Arabidopsis plants.
AB  - Chlorophyll afluorescence has long been used as a noninvasive means to assess
      photosynthetic performance in plants. Pulse-amplitude modulated (PAM) fluorometry
      is one of the most common techniques used to study the induction and quenching of
      chlorophyll fluorescence in physiological studies. In this chapter, we briefly
      describe the basics of PAM fluorometry and how to configure the instrument before
      moving on to some examples of common measurements that can be made using a PAM
      fluorometer. Photosynthetic performance and energy dissipation are compared
      between wild type and the npq4-1mutant by examining the maximum photochemical
      efficiency during high-light stress, the induction and relaxation of non
      photochemical quenching, and by plotting light curves.

PMID- 21863451
TI  - Gas exchange measurements for the determination of photosynthetic efficiency in
      Arabidopsis leaves.
AB  - Photosynthesis is one of the most readily measured metabolic processes in a
      plant, with fluxes being measurable non-invasively even under field conditions.
      In this chapter, two principal approaches are described to measure photosynthesis
      -O2 evolution as determined using an O2 electrode, and CO2 fixation which can be
      quantified using an infrared gas analyser. The advantages and disadvantages of
      these different methods, as applied to Arabidopsis, are discussed, and some major
      forms of analysis are described.

PMID- 21863452
TI  - Measurement of the DeltapH and electric field developed across Arabidopsis
      thylakoids in the light.
AB  - Measurement of the different components of the proton motive force (pmf) gives
      information about the coupling of proton movement within thylakoids to
      chemiosmotic processes such as photophosphorylation and protein transport, as
      well as that relating to the overall quality of a thylakoid preparation. The
      techniques to assess the pmf have been known for many years, as they have been
      applied to the most popular model plants for photosynthetic research. The
      emergence of Arabidopsis thaliana as the prominent model plant in developmental
      and genetics research prompted us to apply these techniques to thylakoids
      isolated from Arabidopsis chloroplasts. We describe here two spectroscopic
      techniques to measure the transmembrane pH gradient and electric field developed
      in the light in Arabidopsis thylakoids.

PMID- 21863453
TI  - Measurement of chloroplast ATP synthesis activity in Arabidopsis.
AB  - There are numerous options for monitoring ATP synthesis in chloroplasts using
      isolated thylakoid membranes, intact chloroplasts, and even whole leaves.
      Currently, the most commonly used method employs isolated thylakoids coupling the
      synthesis of ATP to light emission from luciferin in a reaction catalyzed by
      luciferase. The luciferin-luciferase assay can be highly sensitive and is a
      direct measure of ATP. Another direct measurement of ATP is the incorporation of
      32P into ATP, which, while more technically difficult, has the advantage over the
      luciferin-luciferase assay of being able to distinguish newly synthesized from
      total ATP. The phosphorylation of ADP results in a net decrease in pKa (acid
      disassociation constant) between the reactants and the product ATP, resulting in
      an increase in the pH of the assay media, which can be used as a convenient,
      continuous measurement of ATP synthesis. The formation of DeltaMUH+ across the
      thylakoid membrane and its concomitant dissipation as ATP is synthesized can be
      measured by an electrochromic absorption band shift (ECS) of thylakoid pigments
      measured at 518 nm (Witt, Biochim. Biophys. Acta 505:355-427, 1979; Petty and
      Jackson, Biochim. Biophys. Acta: Bioenergetics 547:463-473, 1979). The first
      order decay time of the ESC can be used to estimate the rate of ATP synthesis
      providing a noninvasive, indirect method for measuring ATP synthase activity that
      can be used with intact leaves.

PMID- 21863454
TI  - Methods for analysis of photosynthetic pigments and steady-state levels of
      intermediates of tetrapyrrole biosynthesis.
AB  - Tetrapyrroles and carotenoids are required for many indispensable functions in
      photosynthesis. Tetrapyrroles are essential metabolites for photosynthesis, redox
      reaction, and detoxification of reactive oxygen species and xenobiotics, while
      carotenoids function as accessory pigments, in photoprotection and in attraction
      to animals. Their branched metabolic pathways of synthesis and degradation are
      tightly controlled to provide adequate amounts of each metabolite
      (carotenoids/tetrapyrroles) and to prevent accumulation of photoreactive
      intermediates (tetrapyrroles). Many Arabidopsis mutants and transgenic plants
      have been reported to show variations in steady-state levels of tetrapyrrole
      intermediates and contents of different carotenoid species. It is a challenging
      task to determine the minute amounts of these metabolites to assess the metabolic
      flow and the activities of both pigment-synthesising and degrading pathways, to
      unravel limiting enzymatic steps of these biosynthetic pathways, and to
      characterise mutants with accumulating intermediates. In this chapter, we present
      a series of methods to qualify and quantify anabolic and catabolic intermediates
      of Arabidopsis tetrapyrrole metabolism, and describe a common method for
      quantification of different plant carotenoid species. Additionally, we introduce
      two methods for quantification of non-covalently bound haem. The approach of
      analysing steady-state levels of tetrapyrrole intermediates in plants, when
      applied in combination with analyses of transcripts, proteins, and enzyme
      activities, enables the biochemical and genetic elucidation of the tetrapyrrole
      pathway in wild-type plants, varieties, and mutants. Steady-state levels of
      tetrapyrrole intermediates are only up to 1/1,000 of the amounts of the
      accumulating end-products, chlorophyll, and haem. Although present in very low
      amounts, the accumulation and availability of tetrapyrrole intermediates have
      major consequences on the physiology and activity of chloroplasts due to their
      additional photoreactive and possible signalling functions. Although adjusted for
      Arabidopsis tetrapyrrole metabolites, the presented methods can also be applied
      for analysis of cyanobacterial and other plant tetrapyrroles.

PMID- 21863455
TI  - Analysis of starch metabolism in chloroplasts.
AB  - Starch is a primary product of photosynthesis in the chloroplasts of many higher
      plants. It plays an important role in the day-to-day carbohydrate metabolism of
      the leaf, and its biosynthesis and degradation represent major fluxes in plant
      metabolism. Starch serves as a transient reserve of carbohydrate which is used to
      support respiration, metabolism, and growth at night when there is no production
      of energy and reducing power through photosynthesis, and no net assimilation of
      carbon. The chapter includes techniques to measure starch amount and its rate of
      biosynthesis, to determine its structure and composition, and to monitor its
      turnover. These methods can be used to investigate transitory starch metabolism
      in Arabidopsis, where they can be applied in combination with genetics and
      systems-level approaches to yield new insight into the control of carbon
      allocation generally, and starch metabolism specifically. The methods can also be
      applied to the leaves of other plants with minimal modifications.

PMID- 21863456
TI  - Analysis of lipid content and quality in Arabidopsis plastids.
AB  - Chloroplasts of plants contain an intricate membrane system, the thylakoids,
      which harbor the complexes of the photosynthetic machinery. Chloroplasts are
      confined by two membranes, the inner and outer envelope. The major glycerolipids
      of chloroplasts are the glycolipids monogalactosyl diacylglycerol (MGD),
      digalactosyl diacylglycerol (DGD), and sulfoquinovosyl diacylglycerol (SQD).
      Furthermore, two phospholipids, phosphatidyl glycerol (PG) and phosphatidyl
      choline (PC), are found in chloroplast membranes. The photosystems and light
      harvesting complexes in the thylakoids are rich in photosynthetic pigments
      (chlorophyll, carotenoids, and xanthophylls) and contain a unique set of
      prenylquinol lipids (tocochromanol/vitamin E, plastoquinol, and
      phylloquinol/vitamin K1). In this chapter, methods for the isolation and
      quantification of chloroplast and leaf glycerolipids and prenylquinol lipids are
      presented. Glycerolipids are separated by thin-layer chromatography prior to
      conversion of the fatty acids into methyl esters. Fatty acid methyl esters are
      subsequently quantified by gas chromatography. Prenylquinol lipids are separated
      by HPLC and quantified by UV absorption (plastoquinol) or fluorescence
      (tocochromanol, phylloquinol).

PMID- 21863457
TI  - Intraoperative monitoring of visual function.

PMID- 21863458
TI  - Postural balance in low back pain patients: criterion-related validity of centre
      of pressure assessed on a portable force platform.
AB  - INTRODUCTION: Altered postural control has been observed in low back pain (LBP)
      patients. They seem to be more dependent on vision when standing. The objective
      of the study was to determine concurrent and predictive validity of measures of
      postural stability in LBP patients. MATERIALS AND METHODS: Centre of Pressure
      (CoP) measurements were tested against pain, fear of pain, and physical function.
      Velocity, anterior-posterior displacement, and the Romberg Ratio obtained on a
      portable force platform were used as measures of postural stability. RESULTS:
      Baseline and 12-week follow-up results of 97 LBP patients were evaluated. The
      correlations between CoP measurements and pain, fear of pain, and physical
      function were poor. There were no significant differences in CoP measurements
      between patients with no change or deterioration and patients with improvement in
      pain and back-specific function. CONCLUSION: This first study of concurrent and
      predictive validity of postural balance in LBP patients revealed no association
      between CoP measures and pain, fear of pain, and physical function.

PMID- 21863459
TI  - Influence of different commercial scaffolds on the in vitro differentiation of
      human mesenchymal stem cells to nucleus pulposus-like cells.
AB  - INTRODUCTION: Cell-based therapies for regeneration of the degenerated
      intervertebral disc (IVD) are an alternative to current surgical intervention.
      Mesenchymal stem cells (MSCs), in combination with a scaffold, might be ideal
      candidates for regenerating nucleus pulposus (NP), the pressure-distributing part
      of the IVD. While the use of growth factors for MSCs differentiation currently
      receives major attention, in this study we compare the performance of sponge-like
      matrixes in supporting cell differentiation into NP-like cells. MATERIALS AND
      METHODS: Four types matrixes approved as medical devices for other applications
      were tested as scaffolds for MSCs: two made of equine or porcine collagen, one of
      gelatin and one of chitosan. Bone marrow-derived human MSCs were seeded in these
      scaffolds or embedded in alginate, as a three-dimensional control. After five
      weeks in culture, NP-like differentiation of the cell-scaffold constructs was
      analyzed by qRT-PCR, histology, total DNA quantification, proteoglycan
      accumulation and immunohistochemistry. RESULTS: MSCs in collagen matrixes and
      gelatin produced more mRNA and proteins of the chondrogenic markers collagen type
      I, collagen type II (COL2) and aggrecan (ACAN), when compared with cells embedded
      in alginate or chitosan. Proteoglycan accumulation and cell survival were also
      higher in collagen and gelatin matrixes. Gene expression results were also
      confirmed by histological and immunohistochemical staining. In contrast to
      alginate control, the gene expression of the undesired bone marker osteopontin
      was lower in all tested groups. In porcine collagen supports, MSC expression
      ratio between COL2/ACAN closely resembled the expression of nucleus pulposus
      cells, but gene expression of recently described NP markers keratin19, PAX1 and
      FOXF1 was lower. CONCLUSIONS: Collagen supports provide a readily available,
      medically approved and effective scaffold for chondrogenic differentiation in
      vitro, but the phenotype of differentiated MSCs is not yet completely equivalent
      to that of NP cells.

PMID- 21863460
TI  - Surgical treatment of severe congenital scoliosis with unilateral unsegmented bar
      by concave costovertebral joint release and both-ends wedge osteotomy via
      posterior approach.
AB  - INTRODUCTION: Congenital scoliosis with unilateral unsegmented bar has remained a
      surgical challenge. If it is treated with a traditional release of the convex
      side and an apical wedge osteotomy, there is a risk of bony bridge fracture on
      the concave side and spine translation during correction maneuvers, which may
      then result in spinal cord injuries. The authors developed a technique that
      consists of a concave-side costovertebral joint release followed by both-ends
      wedge osteotomy via a posterior-only approach. In this article, we describe the
      technique in detail, and present the results of ten patients treated with this
      technique. METHODS: A total of ten patients with congenital scoliosis with
      unilateral unsegmented bar, who had undergone a concave-side costovertebral joint
      release followed by both-end wedge osteotomy via a posterior-only approach were
      followed up for a mean of 34 months (range 26-48 months). The radiographic
      parameters and clinical records were all reviewed and analyzed. RESULTS: Body
      height increased by a mean of 7.3 cm (range 6.0-9.0 cm). The preoperative coronal
      Cobb angle was 102 degrees  (range 83 degrees -139 degrees ) with a mean
      flexibility of 14%. At the most recent follow-up visit, the mean Cobb angle was
      35 degrees  (range 12 degrees -53 degrees ) and the mean correction rate was 66%.
      The coronal imbalance improved from 3.4 cm (range 0.8-6.3 cm) preoperatively to
      1.1 cm (range 0.6-1.8 cm) postoperatively, a 67% correction. There were no
      definite pseudarthroses, no implant failure, and no obvious loss of correction in
      the follow-up period. Complications included one patient with hemopneumothorax
      and another patient with incomplete paralysis of the left lower extremity caused
      by a pedicle screw violating the spinal canal at the T5 level. The screw was
      removed 4 h after the initial operation, and the patient fully recovered after 3
      months. CONCLUSION: We have had good results with our technique of concave-side
      costovertebral joint release and both-end wedge osteotomy. It has the advantage
      of remnant anulus fibrosus, the ligamentum flavum, and the facet joints on the
      concave side serving both as a hinge and to minimize translation of the spine
      ends. It can provide excellent three-dimensional curve correction for patients
      with severe rigid congenital scoliosis with unilateral unsegmented bar.

PMID- 21863461
TI  - The impact of bone mineral density and disc degeneration on shear strength and
      stiffness of the lumbar spine following laminectomy.
AB  - PURPOSE: Laminectomy is a standard surgical procedure for elderly patients with
      symptomatic degenerative lumbar stenosis. The procedure aims at decompression of
      the affected nerves, but it also causes a reduction of spinal shear strength and
      shear stiffness. The magnitude of this reduction and the influence of bone
      mineral density (BMD) and disc degeneration are unknown. We studied the influence
      of laminectomy, BMD, and disc degeneration on shear force to failure (SFF) and
      shear stiffness (SS). METHODS: Ten human cadaveric lumbar spines were obtained
      (mean age 72.1 years, range 53-89 years). Laminectomy was performed either on L2
      or L4, equally divided within the group of ten spines. BMD was assessed by dual X
      ray absorptiometry (DXA). Low BMD was defined as a BMD value below the median.
      Intervertebral discs were assessed for degeneration by MRI (Pfirrmann) and scaled
      in mild and severe degeneration groups. Motion segments L2-L3 and L4-L5 were
      isolated from each spine. SFF and SS were measured, while loading simultaneously
      with 1,600 N axial compression. RESULTS: Low BMD had a significant negative
      effect on SFF. In addition, a significant interaction between low BMD and
      laminectomy was found. In the high BMD group, SFF was 2,482 N (range 1,678-3,284)
      and decreased to 1,371 N (range 940-1,886) after laminectomy. In the low BMD
      group, SFF was 1,339 N (range 909-1,628) and decreased to 761 N (range 561
      1,221). Disc degeneration did not affect SFF, nor did it interact with
      laminectomy. Neither low BMD nor the interaction of low BMD and laminectomy did
      affect SS. Degeneration and its interaction with laminectomy did not
      significantly affect SS. CONCLUSIONS: In conclusion, low BMD significantly
      decreased SFF before and after lumbar laminectomy. Therefore, DXA assessment may
      be an important asset to preoperative screening. Lumbar disc degeneration did not
      affect shear properties of lumbar segments before or after laminectomy.

PMID- 21863462
TI  - The Canadian Occupational Performance Measure's semi-structured interview: its
      applicability to lumbar spinal fusion patients. A prospective randomized clinical
      study.
AB  - BACKGROUND: Although lumbar spinal fusion has been performed for more than 70
      years, few studies have examined rehabilitation strategies for spinal fusion
      patients, and there is only sparse information about the patient's activity level
      after surgery. The Canadian Occupational Performance Measure (COPM) is a
      standardized semi-structured interview, developed to identify patients' problems
      in relation to activities of daily living (ADL). The COPM has neither been
      examined in a randomised clinical study nor employed in relation to lumbar spinal
      fusion patients. We aimed to examine whether or not the use of the semi
      structured interview COPM during in-hospital rehabilitation could: (1) identify
      more ADL-related problems of importance to the patients after discharge from the
      hospital, (2) enhance the patients' ADL performance after discharge from hospital
      METHOD: Eighty-seven patients undergoing a lumbar spinal fusion caused by
      degenerative diseases were randomly assigned to either use of the COPM or to
      standard treatment. RESULTS AND CONCLUSION: Use of the COPM during
      hospitalization helped in identifying more ADL problems encountered by patients
      during the first 3 months post-discharge period as COPM served to identify more
      treatment goals and plans of action. Use of the COPM had no impact on the
      patients' ADL performance, and the difference is so small that COPM may be of
      little clinical consequence.

PMID- 21863463
TI  - Erratum to: Prevalence of sleep disturbance in patients with low back pain.

PMID- 21863464
TI  - Lumbo-pelvic lordosis and the pelvic radius technique in the assessment of spinal
      sagittal balance: strengths and caveats.
AB  - INTRODUCTION: The two main methodologies described for the assessment of spinal
      sagittal alignment are the pelvic radius (PR) technique and that based on
      measures of the Pelvic Incidence (PI) and Spino-Sacral Angle (SSA). Both methods
      stress the fundamental relationship between the anatomical position and
      orientation of the sacrum within the pelvis and the spinal curves above. The aim
      of the current study was to assess the strengths and potential weaknesses of the
      PR technique. The PR technique uses measures based on a line (the PR), drawn
      between the hip axis and the posterior corner of the S1 endplate. The angle
      formed between the PR line and the sacral endplate, PRS1, is a developmental
      measure of sacropelvic morphology. Geometrically, PI and PRS1 are approximately
      complementary angles and both reflect reciprocal alterations in pelvic tilt (for
      PI) or angulation (for PRS1) and the slope of the S1 endplate. The angle formed
      between PR and T12, the PR-T12, reflects a combined measure of pelvic morphology
      and lumbar lordosis. It appears to be a useful measure, which provides a simple
      and rapid assessment of lumbopelvic sagittal balance, but only in the presence of
      a congruent thoracic curvature. MATERIALS AND METHODS: After reviewing the
      literature, published measures made using the PR technique were compared to
      measures taken from a substantial patient population (479 adult patients).
      CONCLUSIONS: Errors can occur using the PR technique if the PRT12 is viewed in
      isolation from the thoracic kyphosis. We found the ratio of the thoracic kyphosis
      to lumbar lordosis (T4-T12/T12-S1) to be a useful predictor of congruent sagittal
      alignment, which may alert the clinician to situations where use of the PR-T12 in
      isolation may be misleading.

PMID- 21863465
TI  - [Ultrasound-guided joint injections in patients with rheumatic diseases].
AB  - Joint and soft tissue injections are routinely performed in daily rheumatology
      practice to establish the diagnosis or as part of the treatment in patients
      suffering from rheumatic diseases. Consequently, joint injections have been
      included in the rheumatology further training curriculum. Despite numerous
      studies demonstrating a poor accuracy and outcome of joint injections guided only
      by clinical examination, most of the injection procedures are still performed in
      a "blind" fashion based on clinical judgment. Ultrasound has evolved as an
      established imaging method in rheumatology within the past decade and is
      considered the preferred imaging modality for joint interventions due to its
      availability and lack of radiation exposure. In this article the indications and
      important aspects of the practical management of ultrasound-guided injections
      performed in daily rheumatology practice are summarized.

PMID- 21863466
TI  - [Morbidity and mortality in systemic rheumatoid diseases: how did they change?].

PMID- 21863469
TI  - [Magnetic resonance imaging in rheumatology].
AB  - Imaging plays a major role in the diagnosis and meanwhile also in the therapy
      control of rheumatic diseases. Besides the commonly used X-ray technique and
      musculoskeletal ultrasound, magnetic resonance imaging (MRI) is able to provide a
      three-dimensional view of musculature, ligaments, tendons, capsules, synovial
      membranes, bones and cartilage with high resolution quality. Therefore, MRI is
      being employed more and more in the early diagnosis of inflammatory joint and
      spinal diseases. Contrast-enhanced MRI enables an assessment of disease activity
      and a differentiation between active and chronic joint manifestation. The
      technical examinations by MRI are these days standardized and invariably
      reproducible. This makes it possible to document the course of a disease and
      allows subsequent treatment decisions. In addition to midfield (>0.5<1.0 T) and
      high field MRI (>1.0 T), low field MRI (<0.5 T) is used in rheumatology as a
      patient-friendly office-based technique.

PMID- 21863467
TI  - [Cardiovascular comorbidity and its risk factors in rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is still associated with an increased mortality mainly
      due to an increase in cardiovascular risk. This increase is not solely explained
      by traditional cardiovascular risk factors but also by disease characteristics,
      e.g. inflammation, positive rheumatoid factor and anti-citrullinated peptide
      antibodies (ACPA). Control of disease activity with disease-modifying drugs
      (DMARDs) was shown to reduce cardiovascular risk in RA patients. Use of non
      steroidal antirheumatic drugs (NSAIDs) and glucocorticoids might be associated
      with an increased risk. The EULAR recommendations for cardiovascular risk
      management in patients with rheumatoid arthritis and other forms of inflammatory
      arthritis have been established. These recommendations are based on national
      guidelines regarding control of traditional cardiovascular risk factors.

PMID- 21863468
TI  - [Changes in mortality and morbidity in systemic lupus erythematosus].
AB  - Systemic lupus erythematosus (SLE) is a chronic multisystem disease and despite
      the improvements in treatment, long-term care still represents a clinical
      challenge. Previous long-running studies have demonstrated a continuous
      improvement in mortality and this trend has persisted over the last two decades.
      However, there still remains a significantly increased mortality in comparison to
      the normal population. Besides deaths caused by disease activity, cardiovascular
      and infectious diseases also play a major role. While deaths caused by SLE
      activity or infections have declined over the years, there has been a notable
      increase in cardiovascular diseases. As the improvement of SLE activity and
      infections can be traced back to individually optimized treatment regimes and the
      more cautious use of steroids, the cardiovascular complications are due to
      accelerated atherosclerosis and the improved survival with ageing of the
      patients. This long-term aspect needs to be taken into account in the early
      stages of disease when treating disease activity and comorbidities.

PMID- 21863470
TI  - [MicroRNAs in B-cells and T-cells as regulators of inflammation].
AB  - MicroRNAs are small non-coding RNAs which are crucial for the fine regulation of
      gene expression. Recent results suggest that these molecules display multifaceted
      functions in B-cells and T-cells in rheumatic inflammatory diseases.

PMID- 21863471
TI  - [Ultrasound-guided puncture : an inexpensive and effective learning model].
AB  - Ultrasound is present in almost any practice and hospital clinic today. In
      clinical practice, puncture of structures, injections of local anesthetics or
      glucocorticoids are frequently performed. However, unguided puncture into tissue
      may have deleterious side-effects if the target is not reached or the drug is not
      injected properly, such as bleeding, traumatization of delicate structures,
      glucocorticoid-induced tendon rupture and skin necrosis. Coordination of eye,
      probe and the manipulation hand needs practice before being used on
      patients.Therefore, we developed an inexpensive, easy to make and effective
      learning model for ultrasound-guided puncture and injections. We describe how the
      model is made and how it can be used to efficiently enhance learning success. It
      was found that a person unskilled in ultrasonography needs about 40-60 coached
      punctures in order to confidently hit the target.This model has already been used
      in our medical education program for rheumatologists, internists, surgeons,
      orthopedic specialists, anesthetists and general practitioners with great
      success.

PMID- 21863475
TI  - The impact of religious connectedness on health-related quality of life in
      patients with diabetic foot ulcers.
AB  - Religious connectedness is common phenomenon in Saudi Arabia and adjacent Gulf
      countries. An observational case control study was designed, enrolling 180 adult
      patients to report the association between religious connectedness and health
      related quality of life (HRQL) in people with and without diabetes and foot
      ulcers. Sixty diabetic patients with foot ulcers (Group I) were compared with
      sixty diabetic patients without foot ulcer (Group II) and sixty healthy subjects
      (Group III) for assessment of their HRQL by using SF-36 questionnaire. The effect
      of religious connectedness was assessed using intrinsic/extrinsic religious
      connectedness scale. HRQL was found to be significantly lower in Group I compared
      with Group II and III as well as in group II compared with group III (P<0.001).
      Group I patients showed a poorer HRQL with increased severity, duration and
      multiplicity of foot ulcers. There was a strong positive relationship between
      religious connectedness and HRQL as indicated by a positive correlation between
      religious connectedness scale and mental, physical component summary scores
      (r=0.66 and 0.59 respectively and P<0.001). While quality of life is generally
      poor in people with diabetic foot ulcers, there exists a strong positive
      relationship between religious connectedness and higher HRQL. These findings may
      have implications on improving outcomes.

PMID- 21863477
TI  - Polymeric nanoparticles for increased oral bioavailability and rapid absorption
      using celecoxib as a model of a low-solubility, high-permeability drug.
AB  - PURPOSE: To demonstrate drug/polymer nanoparticles can increase the rate and
      extent of oral absorption of a low-solubility, high-permeability drug. METHODS:
      Amorphous drug/polymer nanoparticles containing celecoxib were prepared using
      ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were
      characterized using dynamic light scattering, transmission and scanning electron
      microscopy, and differential scanning calorimetry. Drug release and resuspension
      studies were performed using high-performance liquid chromatography.
      Pharmacokinetic studies were performed in dogs and humans. RESULTS: A physical
      model is presented describing the nanoparticle state of matter and release
      performance. Nanoparticles dosed orally in aqueous suspensions provided higher
      systemic exposure and faster attainment of peak plasma concentrations than
      commercial capsules, with median time to maximum drug concentration (Tmax) of
      0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles
      released celecoxib rapidly and provided higher dissolved-drug concentrations than
      micronized crystalline drug. Nanoparticle suspensions are stable for several days
      and can be spray-dried to form dry powders that resuspend in water. CONCLUSIONS:
      Drug/polymer nanoparticles are well suited for providing rapid oral absorption
      and increased bioavailability of BCS Class II drugs.

PMID- 21863478
TI  - Yeast systems biology: the challenge of eukaryotic complexity.
AB  - In this chapter, we present an up-to-date view of the optimal characteristics of
      the yeast Saccharomyces cerevisiae as a model eukaryote for systems biology
      studies, with main molecular mechanisms, biological networks, and sub-cellular
      organization essentially conserved in all eukaryotes, derived from a complex
      common ancestor. The existence of advanced tools for molecular studies together
      with high-throughput experimental and computational methods, most of them being
      implemented and validated in yeast, with new ones being developed, is opening the
      way to the characterization of the core modular architecture and complex networks
      essential to all eukaryotes. Selected examples of the latest discoveries in
      eukaryote complexity and systems biology studies using yeast as a reference model
      and their applications in biotechnology and medicine are presented.

PMID- 21863479
TI  - Saccharomyces cerevisiae: gene annotation and genome variability, state of the
      art through comparative genomics.
AB  - In the early days of the yeast genome sequencing project, gene annotation was in
      its infancy and suffered the problem of many false positive annotations as well
      as missed genes. The lack of other sequences for comparison also prevented the
      annotation of conserved, functional sequences that were not coding. We are now in
      an era of comparative genomics where many closely related as well as more
      distantly related genomes are available for direct sequence and synteny
      comparisons allowing for more probable predictions of genes and other functional
      sequences due to conservation. We also have a plethora of functional genomics
      data which helps inform gene annotation for previously uncharacterised open
      reading frames (ORFs)/genes. For Saccharomyces cerevisiae this has resulted in a
      continuous updating of the gene and functional sequence annotations in the
      reference genome helping it retain its position as the best characterized
      eukaryotic organism's genome. A single reference genome for a species does not
      accurately describe the species and this is quite clear in the case of S.
      cerevisiae where the reference strain is not ideal for brewing or baking due to
      missing genes. Recent surveys of numerous isolates, from a variety of sources,
      using a variety of technologies have revealed a great deal of variation amongst
      isolates with genome sequence surveys providing information on novel genes,
      undetectable by other means. We now have a better understanding of the extant
      variation in S. cerevisiae as a species as well as some idea of how much we are
      missing from this understanding. As with gene annotation, comparative genomics
      enhances the discovery and description of genome variation and is providing us
      with the tools for understanding genome evolution, adaptation and selection, and
      underlying genetics of complex traits.

PMID- 21863480
TI  - Genome-wide measurement of histone H3 replacement dynamics in yeast.
AB  - Chromatin plays critical roles in processes governed in different timescales -
      responses to environmental changes require rapid plasticity, while long-term
      stability through multiple cell generations requires epigenetically heritable
      chromatin. Understanding the dynamic behavior of chromatin is of great interest
      for fields ranging from transcriptional regulation through meiosis and
      gametogenesis. Here, we describe a protocol for measuring histone replacement
      rates genome wide in the budding yeast Saccharomyces cerevisiae. With suitable
      modifications, this protocol could be applied to other organisms, or to
      replacement dynamics of other DNA-associated proteins.

PMID- 21863481
TI  - Genome-wide approaches to studying yeast chromatin modifications.
AB  - The genomes of eukaryotic organisms are packaged into nuclei by wrapping DNA
      around proteins in a structure known as chromatin. The most basic unit of
      chromatin, the nucleosome, consists of approximately 146 bp of DNA wrapped around
      an octamer of histone proteins. The placement of nucleosomes relative to a gene
      can influence the regulation of the transcription of this gene. Furthermore, the
      N-terminal tails of histone proteins are subjected to numerous post-translational
      modifications that are also known to influence gene regulation. In recent years,
      a number of genome-scale approaches to identify modifications to chromatin have
      been developed. Techniques combining chromatin immunoprecipitation (ChIP) with
      microarrays (ChIP-chip) and second-generation sequencing (ChIP-Seq) have led to
      great advances in our understanding of how chromatin modifications contribute to
      gene regulation. Many excellent protocols related to ChIP-chip have been
      published recently (Lieb, J. D. (2003) Genome-wide mapping of protein-DNA
      interactions by chromatin immunoprecipitation and DNA microarray hybridization.
      Methods Mol. Biol. 224, 99-109.). For this reason, we will focus our attention
      here on the application of second-generation sequencing platforms to the study of
      chromatin modifications in yeast. As these genome-scale experiments require both
      wet-lab and bioinformatic components to reach their full potential, we will
      detail both the wet-lab protocols and bioinformatic steps necessary to fully
      conduct genome-scale studies of chromatin modifications.

PMID- 21863482
TI  - Absolute and relative quantification of mRNA expression (transcript analysis).
AB  - In this protocol, we describe a pipeline for transcript analysis in yeast via the
      quantification of mRNA expression levels. In the first section, we consider the
      well-established, proprietary Affymetrix GeneChip(r) approach to generating
      transcriptomics data. In the next section, we concentrate on providing a detailed
      protocol for the validation of these data using quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR). The protocol provides
      suggested examples of hardware, software, and consumables/reagents required to
      perform these experiments. There are of course many other options available using
      alternative approaches (or indeed suppliers), but this protocol is intended to
      provide an approach that is flexible, inexpensive, sensitive, and easy to use.

PMID- 21863483
TI  - Enrichment of unstable non-coding RNAs and their genome-wide identification.
AB  - Cryptic unstable transcripts (CUTs) have been recently described as a major class
      of non-coding RNAs. These transcripts are, however, extremely unstable in normal
      cells and their analyzes pose specific technical problems. In this chapter, after
      a brief introduction discussing general aspects associated with the analysis of
      non-coding RNAs, we provide details of methods to enrich, map, and quantify this
      unconventional class of transcripts.

PMID- 21863484
TI  - Genome-wide transcriptome analysis in yeast using high-density tiling arrays.
AB  - In the last decade, it became clear that transcription goes far beyond that of
      protein-coding genes. Most RNA molecules are transcribed from intergenic regions
      or introns and exhibit much variability in size, expression level, secondary
      structure, and evolutionary conservation. While for several types of non-coding
      RNAs some cellular functions have been reported, like for micro-RNAs and small
      nucleolar RNAs, for most others no indications of function or regulation have so
      far been found. Therefore, the RNA population inside a cell is diverse and
      cryptic and, thus, demands powerful methods to study its composition, abundance,
      and structure. DNA oligonucleotide microarrays have proven to be of great utility
      to study transcription of genes in various organisms. Recently, due to
      advancement in microarray technology, tiling microarrays that extend
      transcription measurement to genomic regions beyond protein-coding genes were
      designed for several species. The Saccharomyces cerevisiae yeast tiling array
      contains overlapping probes across the full genomic sequence, with consecutive
      probes starting every 8 bp on average on each strand, enabling strand-specific
      measurement of transcription from a full eukaryotic genome. Here, we describe the
      methods used to extract yeast RNA, convert it into first-strand cDNA, fragment,
      and label it for hybridization to the tiling array. This protocol will enable
      researchers not only to study which genes are expressed and to what levels, but
      also to identify non-coding RNAs and to study the structure of transcripts
      including their untranslated regions, alternative start, stop, and processing
      sites. This information will allow understanding their roles inside cells.

PMID- 21863485
TI  - RNA sequencing.
AB  - This chapter describes the RNA sequencing (RNA-Seq) protocol, whereby RNA from
      yeast cells is prepared for sequencing on an Illumina Genome Analyzer. The
      protocol can easily be altered to use RNA from a different organism. This chapter
      covers RNA extraction, cDNA synthesis, cDNA fragmentation, and Illumina cDNA
      library generation and contains some brief remarks on bioinformatic analysis.

PMID- 21863476
TI  - Inhibitors of succinate: quinone reductase/Complex II regulate production of
      mitochondrial reactive oxygen species and protect normal cells from ischemic
      damage but induce specific cancer cell death.
AB  - Succinate:quinone reductase (SQR) of Complex II occupies a unique central point
      in the mitochondrial respiratory system as a major source of electrons driving
      reactive oxygen species (ROS) production. It is an ideal pharmaceutical target
      for modulating ROS levels in normal cells to prevent oxidative stress-induced
      damage or alternatively,increase ROS in cancer cells, inducing cell death.The
      value of drugs like diazoxide to prevent ROS production,protecting normal cells,
      whereas vitamin E analogues promote ROS in cancer cells to kill them is
      highlighted. As pharmaceuticals these agents may prevent degenerative disease and
      their modes of action are presently being fully explored. The evidence that
      SDH/Complex II is tightly coupled to the NADH/NAD+ ratio in all cells,impacted by
      the available supplies of Krebs cycle intermediates as essential NAD-linked
      substrates, and the NAD+-dependent regulation of SDH/Complex II are reviewed, as
      are links to the NAD+-dependent dehydrogenases, Complex I and the E3
      dihiydrolipoamide dehydrogenase to produce ROS. This review collates and
      discusses diverse sources of information relating to ROS production in different
      biological systems, focussing on evidence for SQR as the main source of ROS
      production in mitochondria, particularly its relevance to protection from
      oxidative stress and to the mitochondrial-targeted anti cancer drugs (mitocans)
      as novel cancer therapies [corrected].

PMID- 21863486
TI  - Polyadenylation state microarray (PASTA) analysis.
AB  - Nearly all eukaryotic mRNAs terminate in a poly(A) tail that serves important
      roles in mRNA utilization. In the cytoplasm, the poly(A) tail promotes both mRNA
      stability and translation, and these functions are frequently regulated through
      changes in tail length. To identify the scope of poly(A) tail length control in a
      transcriptome, we developed the polyadenylation state microarray (PASTA) method.
      It involves the purification of mRNA based on poly(A) tail length using thermal
      elution from poly(U) sepharose, followed by microarray analysis of the resulting
      fractions. In this chapter we detail our PASTA approach and describe some methods
      for bulk and mRNA-specific poly(A) tail length measurements of use to monitor the
      procedure and independently verify the microarray data.

PMID- 21863487
TI  - Enabling technologies for yeast proteome analysis.
AB  - Whilst the study of yeast genomes and transcriptomes is in an advanced state,
      there is still much to learn about the resulting proteins in terms of cataloging,
      characterization of post-translational modifications, turnover, and the dynamics
      of sub-cellular localization and interactions. Analysis of the transcripts gives
      little insight into function or diversity as changes in RNA levels do not always
      correlate with the resulting protein abundance. A number of global and targeted
      attempts have been made to catalog and characterize the yeast proteome and we
      describe here the methods used to gain a greater understanding of the yeast
      proteome. This comprehensive review also describes future approaches that will
      aid completion in identifying and characterizing the remaining 20% of the
      undetermined yeast proteome as well as giving new insight into protein dynamics.

PMID- 21863488
TI  - Protein turnover methods in single-celled organisms: dynamic SILAC.
AB  - Early achievements in proteomics were qualitative, typified by the identification
      of very small quantities of proteins. However, as the subject has developed,
      there has been a pressure to develop approaches to define the amounts of each
      protein--whether in a relative or an absolute sense. A further dimension to
      quantitative proteomics embeds the behavior of each protein in terms of its
      turnover. Virtually every protein in the cell is in a dynamic state, subject to
      continuous synthesis and degradation, the relative rates of which control the
      expansion or the contraction of the protein pool, and the absolute values of
      which dictate the temporal responsiveness of the protein pool. Strategies must
      therefore be developed to assess the turnover of individual proteins in the
      proteome. Because a protein can be turning over rapidly even when the protein
      pool is in steady state, the only acceptable approach to measure turnover is to
      use metabolic labels that are incorporated or lost from the protein pool as it is
      replaced. Using metabolic labeling on a proteome-wide scale in turn requires
      metabolic labels that contain stable isotopes, the incorporation or loss of which
      can be assessed by mass spectrometry. A typical turnover experiment is complex.
      The choice of metabolic label is dictated by several factors, including abundance
      in the proteome, metabolic redistribution of the label in the precursor pool, and
      the downstream mass spectrometric analytical protocols. Key issues include the
      need to control and understand the relative isotope abundance of the precursor,
      the optimization of label flux into and out of the protein pool, and a sampling
      strategy that ensures the coverage of the greatest range of turnover rates.
      Finally, the informatics approaches to data analysis will not be as
      straightforward as in other areas of proteomics. In this chapter, we will discuss
      the principles and practice of workflow development for turnover analysis,
      exemplified by the development of methodologies for turnover analysis in the
      model eukaryote Saccharomyces cerevisiae.

PMID- 21863489
TI  - Protein-protein interactions and networks: forward and reverse edgetics.
AB  - Phenotypic variations of an organism may arise from alterations of cellular
      networks, ranging from the complete loss of a gene product to the specific
      perturbation of a single molecular interaction. In interactome networks that are
      modeled as nodes (macromolecules) connected by edges (interactions), these
      alterations can be thought of as node removal and edge-specific or "edgetic"
      perturbations, respectively. Here we present two complementary strategies,
      forward and reverse edgetics, to investigate the phenotypic outcomes of edgetic
      perturbations of binary protein-protein interaction networks. Both approaches are
      based on the yeast two-hybrid system (Y2H). The first allows the determination of
      the interaction profile of proteins encoded by alleles with known phenotypes to
      identify edgetic alleles. The second is used to directly isolate edgetic alleles
      for subsequent in vivo characterization.

PMID- 21863490
TI  - Use of proteome arrays to globally identify substrates for E3 ubiquitin ligases.
AB  - Ubiquitin-protein ligases (E3s) are responsible for target recognition and
      subsequent modification of selected substrates within the ubiquitin proteasomal
      system (UPS). Substrates of this pathway are covalently modified by the
      attachment of ubiquitin usually onto Lys residues. As a result, these modified
      proteins can be targeted for degradation, endocytosis, protein sorting,
      subnuclear trafficking, or other fates. Despite the advancements in understanding
      the underlying mechanisms of the ubiquitin system, the substrates of most E3
      enzymes remain largely unknown. Here, we describe the development of a high
      throughput method to identify in vitro substrates for E3 ligases on a global
      proteomic scale. The enzymatic activity (ubiquitylation) and binding of ubiquitin
      ligases to their substrates are performed using protein (proteome) microarrays as
      the experimental platform, and using Nedd4/Rsp5 family members as examples of
      HECT E3 ligases. The in vitro ubiquitylation and binding substrates identified in
      these screens can provide invaluable insight into the cellular pathways in which
      E3 ligases participate.

PMID- 21863491
TI  - Fit-for-purpose quenching and extraction protocols for metabolic profiling of
      yeast using chromatography-mass spectrometry platforms.
AB  - Metabolomics involves the investigation of the intracellular (endometabolome) and
      extracellular (exometabolome) pools of metabolites in biological systems. Methods
      to sample the exometabolome and to quench metabolism and extract intracellular
      metabolites for the model eukaryote Saccharomyces cerevisiae are presented here.
      These methods have been developed and validated to provide a fit-for-purpose
      protocol for global analyses of the S. cerevisiae metabolome. The protocol allows
      the extraction of a wide variety of metabolite classes and provides reproducible
      results to allow relative and semi-quantitative comparisons between samples of
      different origin. For exometabolome studies, fast sampling and separation of
      cells by syringe filtration is recommended. For endometabolome studies, fast
      quenching of intracellular metabolism is performed using a 60:40 (v/v)
      methanol:aqueous ammonium hydrogen carbonate solution at -48  degrees C.
      Extraction of intracellular metabolites is performed using multiple freeze/thaw
      cycles in a 60:40 (v/v) methanol:water solution at temperatures lower than 0 
      degrees C.

PMID- 21863492
TI  - The automated cell: compound and environment screening system (ACCESS) for
      chemogenomic screening.
AB  - The automated cell, compound and environment screening system (ACCESS) was
      developed as an automated platform for chemogenomic research. In the yeast
      Saccharomyces cerevisiae, a number of genomic screens rely on the modulation of
      gene dose to determine the mode of action of bioactive compounds or the effects
      of environmental/compound perturbations. These and other phenotypic experiments
      have been shown to benefit from high-resolution growth curves and a highly
      automated controlled environment system that enables a wide range of multi-well
      assays that can be run over many days without any manual intervention.
      Furthermore, precise control of drug dosing, timing of drug exposure, and precise
      timing of cell harvesting at specific generation times are important for optimal
      results. Some of these benefits include the ability to derive fine distinctions
      between growth rates of mutant strains (1) and the discovery of novel compounds
      and drug targets (2). The automation has also enabled large-scale screening
      projects with over 100,000 unique compounds screened to date including a thousand
      genome-wide screens (3). The ACCESS system also has a diverse set of software
      tools to enable users to set up, run, annotate, and evaluate complex screens with
      minimal training.

PMID- 21863493
TI  - Competition experiments coupled with high-throughput analyses for functional
      genomics studies in yeast.
AB  - Competition experiments are an effective way to provide a measurement of the
      fitness of yeast strains. The availability of the Saccharomyces cerevisiae yeast
      knock-out (YKO) deletion collection allows scientists to retrieve fitness data
      for the ~6,000 S. cerevisiae genes at the same time in a given environment. The
      molecular barcodes, characterizing each yeast mutant, serve as strain
      identifiers, which can be detected in a single microarray analysis. Competition
      experiments in continuous culture using chemically defined media allow a more
      specific discrimination of the strains based on their fitness profile. With this
      high-throughput approach, a series of genes that, when one allele is missing,
      result in either defective (haplo-insufficient) or favored (haplo-proficient)
      growth phenotype have been discovered, for each nutrient-limiting condition
      tested. While haplo-insufficient genes seemed to overlap largely across all the
      media used, the haplo-proficient ones seem to be more environment specific. For
      example, genes involved in the protein secretion pathway were highly haplo
      insufficient in all the contexts, whereas most of the genes encoding for
      proteasome components showed a haplo-proficient phenotype specific to nitrogen
      limiting conditions. In this chapter, the method used for implementation of
      competition experiments for high-throughput studies in yeast is presented.

PMID- 21863494
TI  - Fluorescence fluctuation spectroscopy and imaging methods for examination of
      dynamic protein interactions in yeast.
AB  - Protein interactions are inherently dynamic. In no system is this more true and
      important than in signaling pathways, where spatial and temporal control of
      specific protein interactions is key to signaling specificity and timing. While
      genetic and biochemical interactions form a necessary and important starting
      point for deciphering interactions among signaling components, they struggle to
      provide precise information of where and when interactions occur in a live cell
      setting. In contrast, live cell fluorescence studies such as those outlined below
      are able to provide quantitative information on the strength, nature, timing, and
      location of homotypic and heterotypic protein interactions.

PMID- 21863495
TI  - Nutritional control of cell growth via TOR signaling in budding yeast.
AB  - Cell growth is highly regulated and its deregulation is related to many human
      diseases such as cancer. Nutritional cues stimulate cell growth through
      modulation of TOR (target of rapamycin) signaling pathway. At the center of this
      pathway is a large serine/threonine protein kinase TOR, which forms two distinct
      functional complexes TORC1 and TORC2 in a cell. TORC1 senses the environmental
      nutrient quality/quantity and transmits the growth signals to multiple effectors
      to regulate a broad spectrum of biological processes including translation
      initiation, ribosome biogenesis, autophagy, nutrient uptake, and metabolism. By
      using budding yeast as a model, recent studies began to elucidate the complexity
      of the TOR signaling pathway.

PMID- 21863496
TI  - Computational yeast systems biology: a case study for the MAP kinase cascade.
AB  - Cellular networks and processes can be mathematically described and analyzed in
      various ways. Here, the case example of a MAP kinase (MAPK) cascade is used to
      detail steps in the formulation of a system of ordinary differential equations
      governing the temporal behavior of a signal transduction pathway after
      stimulation. Different analysis methods for the model are explained and
      demonstrated, such as stoichiometric analysis, sensitivity analysis, or studying
      the effect of deletions and protein overexpression. Finally, a perspective on
      standards concerning modeling in systems biology is given.

PMID- 21863497
TI  - Standards, tools, and databases for the analysis of yeast 'omics data.
AB  - One of the major objectives of systems biology is the development of mathematical
      models for the quantitative description of complex biological systems, such as
      living cells. Biological data and software tools for the design, analysis, and
      simulation of models are two basic ingredients for the new field of systems
      biology. In this chapter we give an overview of databases and repositories that
      provide valuable information for the integrative analysis and modeling of data
      generated by the different omics techniques. We also provide a review of the most
      popular software tools currently used in computational systems biology studies.
      Standards for the annotation of biological data and for the analysis and exchange
      of models are fundamental for the success of systems biology and provide the glue
      that connects experimental data with mathematical models. We also discuss some
      broad trends regarding where systems biology is heading to.

PMID- 21863498
TI  - A computational method to search for DNA structural motifs in functional genomic
      elements.
AB  - The rapidly increasing availability of DNA sequence data from modern high
      throughput experimental techniques has created the need for computational
      algorithms to aid in motif discovery in genomic DNA. Such algorithms are
      typically used to find a statistical representation of the nucleotide sequence of
      the target site of a DNA-binding protein within a collection of DNA sequences
      that are thought to contain segments to which the protein is bound. A major
      assumption of these algorithms is that the protein recognizes the primary order
      of nucleotides in the sequence. However, proteins can also recognize the three
      dimensional shape and structure of DNA. To account for this, we developed a
      computational method to predict the local structural profiles of any set of DNA
      sequences and then to search within these profiles for common DNA structural
      motifs. Here we describe the details of this method and use it to find a DNA
      structural motif in the Saccharomyces cerevisiae yeast genome that is associated
      with binding of the transcription factor RLM1, a component of the protein kinase
      C-mediated MAP kinase pathway.

PMID- 21863499
TI  - High-throughput analyses and curation of protein interactions in yeast.
AB  - The yeast Saccharomyces cerevisiae is the model organism in which protein
      interactions have been most extensively analyzed. The vast majority of these
      interactions have been characterized by a variety of sophisticated high
      throughput techniques probing different aspects of protein association. This
      chapter summarizes the major techniques, highlights their complementary nature,
      discusses the data they produce, and highlights some of the biases from which
      they suffer. A main focus is the key role played by computational methods for
      processing, analyzing, and validating the large body of noisy data produced by
      the experimental procedures. It also describes how computational methods are used
      to extend the coverage and reliability of protein interaction data by integrating
      information from heterogeneous sources and reviews the current status of
      literature-curated data on yeast protein interactions stored in specialized
      databases.

PMID- 21863500
TI  - Noise in biological systems: pros, cons, and mechanisms of control.
AB  - Genetic regulatory circuits are often regarded as precise machines that
      accurately determine the level of expression of each protein. Most experimental
      technologies used to measure gene expression levels are incapable of testing and
      challenging this notion, as they often measure levels averaged over entire
      populations of cells. Yet, when expression levels are measured at the single cell
      level of even genetically identical cells, substantial cell-to-cell variation (or
      "noise") may be observed. Sometimes different genes in a given genome may display
      different levels of noise; even the same gene, expressed under different
      environmental conditions, may display greater cell-to-cell variability in
      specific conditions and more tight control in other situations. While at first
      glance noise may seem to be an undesired property of biological networks, it
      might be beneficial in some cases. For instance, noise will increase functional
      heterogeneity in a population of microorganisms facing variable, often
      unpredictable, environmental changes, increasing the probability that some cells
      may survive the stress. In that respect, we can speculate that the population is
      implementing a risk distribution strategy, long before genetic heterogeneity
      could be acquired. Organisms may have evolved to regulate not only the averaged
      gene expression levels but also the extent of allowed deviations from such an
      average, setting it at the desired level for every gene under each specific
      condition. Here we review the evolving understanding of noise, its molecular
      underpinnings, and its effect on phenotype and fitness--when it can be
      detrimental, beneficial, or neutral and which regulatory tools eukaryotic cells
      may use to optimally control it.

PMID- 21863501
TI  - Genome-scale integrative data analysis and modeling of dynamic processes in
      yeast.
AB  - Building a dynamic model of a complete biological cell is one of the great
      challenges of the 21st century. While this objective could appear unrealistic
      until recently, considerable improvements in high-throughput data collection
      techniques, computational performance, data integration, and modeling approaches
      now allow us to consider it within reach in the near future. In this chapter, we
      review recent developments that pave the way toward the construction of genome
      scale dynamic models. We first describe methodologies for the integration of
      heterogeneous "omics" datasets, which enable the interpretation of cellular
      activity at the genome scale and in fluctuating conditions, providing the
      necessary input to models. We subsequently discuss principles of such models and
      describe a series of approaches that open perspectives toward the construction of
      genome-scale dynamic models.

PMID- 21863502
TI  - Genome-scale metabolic models of Saccharomyces cerevisiae.
AB  - Systematic analysis of Saccharomyces cerevisiae metabolic functions and pathways
      has been the subject of extensive studies and established in many aspects. With
      the reconstruction of the yeast genome-scale metabolic (GSM) network and in
      silico simulation of the GSM model, the nature of the underlying cellular
      processes can be tested and validated with the increasing metabolic knowledge.
      GSM models are also being exploited in fundamental research studies and
      industrial applications. In this chapter, the principle concepts for
      construction, simulation and validation of GSM models, progressive applications
      of the yeast GSM models, and future perspectives are described. This will support
      and encourage researchers who are interested in systemic analysis of yeast
      metabolism and systems biology.

PMID- 21863503
TI  - Representation, simulation, and hypothesis generation in graph and logical models
      of biological networks.
AB  - This chapter presents a discussion of metabolic modeling from graph theory and
      logical modeling perspectives. These perspectives are closely related and focus
      on the coarse structure of metabolism, rather than the finer details of system
      behavior. The models have been used as background knowledge for hypothesis
      generation by Robot Scientists using yeast as a model eukaryote, where
      experimentation and machine learning are used to identify additional knowledge to
      improve the metabolic model. The logical modeling concept is being adapted to
      cell signaling and transduction biological networks.

PMID- 21863504
TI  - Use of genome-scale metabolic models in evolutionary systems biology.
AB  - One of the major aims of the nascent field of evolutionary systems biology is to
      test evolutionary hypotheses that are not only realistic from a population
      genetic point of view but also detailed in terms of molecular biology mechanisms.
      By providing a mapping between genotype and phenotype for hundreds of genes,
      genome-scale systems biology models of metabolic networks have already provided
      valuable insights into the evolution of metabolic gene contents and phenotypes of
      yeast and other microbial species. Here we review the recent use of these
      computational models to predict the fitness effect of mutations, genetic
      interactions, evolutionary outcomes, and to decipher the mechanisms of mutational
      robustness. While these studies have demonstrated that even simplified models of
      biochemical reaction networks can be highly informative for evolutionary
      analyses, they have also revealed the weakness of this modeling framework to
      quantitatively predict mutational effects, a challenge that needs to be addressed
      for future progress in evolutionary systems biology.

PMID- 21863505
TI  - Contributions of Saccharomyces cerevisiae to understanding mammalian gene
      function and therapy.
AB  - Due to its genetic tractability and ease of manipulation, the yeast Saccharomyces
      cerevisiae has been extensively used as a model organism to understand how
      eukaryotic cells grow, divide, and respond to environmental changes. In this
      chapter, we reasoned that functional annotation of novel genes revealed by
      sequencing should adopt an integrative approach including both bioinformatics and
      experimental analysis to reveal functional conservation and divergence of
      complexes and pathways. The techniques and resources generated for systems
      biology studies in yeast have found a wide range of applications. Here we focused
      on using these technologies in revealing functions of genes from mammals, in
      identifying targets of novel and known drugs and in screening drugs targeting
      specific proteins and/or protein-protein interactions.

PMID- 21863506
TI  - [Patient education - evidence-based patient information - a novelty in surgery?].

PMID- 21863507
TI  - [Mediation - Antigone and discussion of the conflict].

PMID- 21863508
TI  - [How can we further improve the long-term prognosis of our tumour patients?].

PMID- 21863509
TI  - [Oesophageal cancer: current status of multimodality therapy].
AB  - Multimodality treatment options have been widely promoted in the therapy for
      locally advanced oesophageal cancer (cT3/4Nx). Generally neoadjuvant chemotherapy
      and combined radiochemotherapy are frequently used in this setting. The recent
      meta-analyses evaluating randomised trials of different neoadjuvant therapy
      protocols prior to surgery for patients with locally advanced oesophageal cancer
      showed only a modest improvement in survivial of 5-10% survival at 5 years. In
      contrast, the meta-analyses reveal that patients with excellent histopathological
      responses seem to highly benefit from neoadjuvant regimens. Patients with poor
      histopathological responses have no benefit but rather disadvantegeous prognoses.
      Therefore, predictive markers to allow individualisation of multimodality
      treatment in locally advanced esophageal cancer are urgently needed.

PMID- 21863510
TI  - [Multimodal therapy for colon cancer: state of the art].
AB  - In UICC stage I a selected group of patients with T1 tumours and a low risk
      profile regarding simultaneous lymph node metastases can be treated by endoscopic
      resection alone, if the tumour is thereby completely removed. In UICC stage II an
      adjuvant chemotherapy (CT) should not be routinely performed. However, in high
      risk UICC stage II patients (T4 tumour, less than 12 examined lymph nodes,
      emergency surgery, intraoperative tumour perforation), an adjuvant CT with
      infusional 5-FU/FA should be recommended. The state of the art in UICC stage III
      is an adjuvant CT with FOLFOX. In this tumour stage no beneficial effect of CT
      involving irinotecan or monoclonal antibodies has been documented. Due to CT
      induced side effects an infusional 5-FU/FA protocol or oral capecitabine should
      be given in patients older than 70 years. In stage UICC IV with resectable liver
      metastases, surgical resection of the primary tumour and the metastases should be
      implemented. Since no conclusive data are currently available regarding the
      beneficial effect of neoadjuvant, perioperative or adjuvant CT in this setting,
      the therapeutic strategy should be individually discussed between surgeons and
      oncologists (tumour board). In cases of non-resectable liver metastases a
      neoadjuvant CT should be performed, preferentially with a FOLFOX protocol in
      combination with targeted therapies, i.e., the monoclonal antibody cetuximab,
      aimed at tumour regression with radical metastasectomy as the secondary intent
      (R0). Patients with UICC stage II colon cancer and microsatellite instability
      (MSI) apparently experience a better prognosis but do not profit from an adjuvant
      CT with 5-FU/FA alone. If a CT is under consideration for these patients, the MSI
      status should be determined on tumour tissue. In cases of a positive result a
      combination CT, i.e., with FOLFOX, should be given. The relevance of the MSI
      status in other tumour stages is as yet unknown. Before targeted therapies, i.e.,
      cetuximab or panitumumab, are initiated, the KRAS status needs to be determined,
      since therapies with antibodies against the epithelial growth factor receptor
      (EGFR) are only effective in tumours bearing the KRAS wild-type.

PMID- 21863511
TI  - [Rectal cancer: current status of multimodal therapy--when and how?].
AB  - Preoperative 5-fluorouracil-based radiochemotherapy (RCT) followed by quality
      assessed total mesorectal excision (TME surgery) are the two most important
      elements of multimodal treatment for patients with locally advanced rectal cancer
      (UICC stages II and III). The optimum sequence of these neoadjuvant modalities
      complemented by adjuvant (postoperative) chemotherapy, has been addressed in
      several randomised trials. Especially within the trials of the German Rectal
      Cancer Study Group (GRCSG), preoperative RCT has been shown to be superior to
      postoperative treatment for a variety of endpoints (pathologically confirmed
      complete tumour remission (pCR), RCT-induced tumour regression, R0 resection
      rates (including circumferential resection margins) and long-term locoregional
      control). This neoadjuvant multimodal strategy has decreased the 5-year and 10
      year local recurrence rates below 10%, and the development of distant metastases
      (e.g., 35% to 45% liver metastases) remains the predominant reason for failure.
      Furthermore, approximately 25% of patients do not receive adjuvant chemotherapy,
      mainly due to surgical complications, patients' refusal or the investigator's
      discretion. Thus, today, integrating more effective systemic therapy into
      (preoperative) multimodal regimens is the most accepted challenge! But from the
      clinical point of view this demand is also a dilemma. The question to be
      addressed is how and when to apply intensified systemic therapy with adequate
      dosage and intensity as well as acceptable treatment-associated toxicity. The
      increase of therapeutic options requires valid predictive biomarkers that may
      help to stratify patients into regimens associated with low toxicity (5-FU
      monotherapy alone) or into more intensified treatment for better long-term
      outcome. In summary, the use of biomarkers for individualised risk-adapted
      treatment is one of the most promising areas of clinical investigations, not only
      in rectal cancer. The assessment of individual tumour response, toxicity, and
      prognosis during multimodal treatment of rectal cancer as a model of a very
      common solid tumour offers radiooncologists, surgeons, pathologists,
      gastroenterologists as well as oncologists immense insights into the under
      standing of tumour biology.

PMID- 21863512
TI  - [Current status of multimodal therapy for colorectal liver metastases].
AB  - Surgical resection is the only chance of cure for patients with colorectal liver
      metastases und significantly improves patient survival. The percentage of
      patients who can undergo curative resection as well as the survival after liver
      resection can be increased by using modern multimodal treatment algorithms. This
      has been achieved by not only innovations in pre- and postoperative chemotherapy
      but also by new surgical and interventional techniques and last but not least by
      individualisation of chemotherapeutic regimens. Due to the high number of new
      treatment modalities, a generally accepted treatment algorithm cannot be provided
      so far for all subgroups of the inhomogeneous group of patients with colorectal
      liver metastases. In the present review the current status of multimodal therapy
      is outlined and the pending questions mentioned.

PMID- 21863516
TI  - Preoperative evaluation of the deep cerebral veins using 3-tesla magnetic
      resonance imaging.
AB  - BACKGROUND: Surgical treatment of deep-seated tumors such as supratentorial
      intraventricular and thalamic-pineal-tectal region tumors carries a risk of
      postoperative deficits due to possible damage to deep cerebral veins including
      the internal cerebral vein. It is often difficult to identify whether the vessel
      encountered during surgery needs to be preserved or not through the small
      operative field. Therefore, preoperative evaluation of deep venous structures is
      important. We evaluated the usefulness of 3-Tesla magnetic resonance imaging (3 T
      MRI) for this purpose. METHODS: First, the ability to detect deep venous
      structures was compared with both 3-dimensional computed tomographical
      angiography (3D-CTA) and 3 T MRI in patients without any damage to deep venous
      structures. Images of 7 consecutive patients suffering from insulo-opercular
      gliomas who underwent both imaging modes for the identification of lateral
      striate arteries were reconstructed for evaluation of the deep cerebral veins.
      Subsequently, surgery for tumors at the supratentorial intraventricular and
      thalamic-pineal-tectal regions was prospectively performed with preoperative
      evaluation of deep venous system only using 3 T MRI. RESULTS: Information on the
      deep venous systems acquired by 3 T MRI was as useful as that acquired by 3D-CTA.
      Until today, we have treated 8 cases of supratentorial intraventricular and
      thalamic-pineal-tectal region tumors with preoperative evaluation of the deep
      venous system using 3 T MRI without any morbidity. CONCLUSION: Information on the
      deep venous system obtained with 3 T MRI aids the surgery of supratentorial
      intraventricular and thalamic-pineal-tectal region tumors. As the required
      sequences of 3 T MRI are same as those necessary for the neuronavigation system,
      and 3 T MRI can be achieved without the use of iodine-based contrast agents, 3 T
      MRI can be an alternative for preoperative evaluation of the deep venous systems.

PMID- 21863513
TI  - [Gastrointestinal stromal tumour (GIST): current standards in multimodal
      management].
AB  - Gastrointestinal stromal tumours (GIST) are the most frequent mesenchymal tumours
      of the gastrointestinal tract. The gold standard therapy is their complete
      surgical removal with safety margins of 1-2 cm. Intraoperative damage to the
      tumour must be avoided because tumour rupture carries a very high risk of
      peritoneal spread. Since metastases to lymph nodes in general does not occur in
      GIST a lymph node dissection is not indicated. Depending on the size of the
      tumour, the number of mitoses and the localisation of the primary tumour, the
      risk of recurrence after potentially curative resection is considerable in many
      cases. Patients with intermediate and high risk according to Miettinens
      classification should receive adjuvant treatment with imatinib. Exceptions are
      those patients whose tumours exhibit a mutation in exon 18, D842V of PDGFRA.
      According to current data the therapy is continued for 3 years. This leads not
      only to a significant improvement of the progression-free survival in comparison
      to therapy for 1 year but also, especially, to an improvement of overall
      survivial. In the case of local advanced tumours that can only be resected by a
      mutilation operation, a primary systemic therapy with imatinib should be
      initiated on account of its extremely high efficacy. Standard therapy for local
      advanced or metastasizing GIST is imatinib at a dose of 400 mg/day. Patients with
      mutations in KIT exon 9 should be treated with 800 mg imatinib/day, since they
      profit from a significantly longer progression-free survival. Therapy with
      imatinib should always be continued up to progression or intolerance. In the case
      of progression under 400 mg imatinib the ESMO guidelines recommend a dose
      increase to 800 mg/day as about a third of the patients respond to this higher
      dose. In the case of further progression a switch to second-line therapy with
      sunitinib is recommended. After exploitation of all registered therapy options
      the patients should be offered an experimental therapy within the framework of a
      clinical trial.

PMID- 21863517
TI  - Endoscopic vascular decompression of the trigeminal nerve.
AB  - BACKGROUND: Microvascular decompression is an effective method of treatment in
      trigeminal neuralgia. It may fail if a compressing vessel is overlooked during
      surgery. The endoscope has an edge over the microscope in visualizing such
      conflicts. MATERIALS AND METHODS: This is a prospective study of 51 patients.
      Preoperative computed tomography and magnetic resonance imaging scans were
      performed in all the cases. A 4 - 5 cm retroauricular skin incision was made and
      an about 3 cm craniectomy was performed. A 0 degrees  4 mm telescope supported by
      the holder was used after the dural opening. A 2 by 6 cm sheet prepared from hand
      gloves was used to protect the brain. A Karl Storz 30 degrees  telescope was used
      for the visualization of the trigeminal nerve from the pons to Meckel's cave and
      dissection of the anterior conflict. Small pieces of dura patch were interposed
      between the nerve and the vessel. The microscope was not used at any stage. Post
      operative infection, cerebrospinal fluid leak, cranial nerve deficit, failure of
      procedure in terms of pain relieves and recurrences of pain were recorded. The
      follow-up period ranged from 24 to 55 months with an average of 36 months.
      RESULTS: There was no mortality or any major permanent complications. The
      duration of stay ranged from 3 to 10 days with an average of 3.6 days. The pain
      was relieved in 48 patients. CONCLUSION: Endoscopic vascular decompression is an
      effective and safe alternative to endoscopic assisted microvascular decompression
      in trigeminal neuralgia.

PMID- 21863518
TI  - Frameless image-guided neuroendoscopy training in real simulators.
AB  - BACKGROUND: Over the last decade, neuroendoscopy has re-emerged as an interesting
      option in the management of intraventricular lesions in both children and adults.
      Nonetheless, as it has become more difficult to use cadaveric specimens in
      training, the development of alternative methods was vital. The aim of this study
      was to analyze the performance of a real simulator, in association with image
      guided navigation, as a teaching tool for the training of intraventricular
      endoscopic procedures. METHODS: 3 real simulators were built using a special type
      of resin. 1 was designed to represent the abnormally enlarged ventricles, making
      it possible for a third ventriculostomy to be performed. The remaining 2 were
      designed to simulate a person's skull and brain bearing intraventricular lesions,
      which were placed as follows: in the foramen of Monro region, in the frontal and
      occipital horns of the lateral ventricles and within the third ventricle. In all
      models, MRI images were obtained for navigation guidance. Within the ventricles,
      the relevant anatomic structures and the lesions were identified through the
      endoscope and compared with the position given by the navigation device. The next
      step consisted of manipulating the lesions, using standard endoscopic techniques.
      RESULTS: We observed that the models were MRI compatible, easy and safe to
      handle. They nicely reproduced the intraventricular anatomy and brain
      consistence, as well as simulated intraventricular lesions. The image-based
      navigation was efficient in guiding the surgeon through the endoscopic procedure,
      allowing the selection of the best approach as well as defining the relevant
      surgical landmarks for each ventricular compartment. Nonetheless, as expected,
      navigation inaccuracies occurred. After the training sessions the surgeons felt
      they had gained valued experience by dealing with intraventricular lesions
      employing endoscopic techniques. CONCLUSION: The use of real simulators in
      association with image-guided navigation proved to be an effective tool in
      training for neuroendoscopy.

PMID- 21863519
TI  - Cranial bone flap fixation using a new device (Cranial LoopTM).
AB  - BACKGROUND: Fixation of bone flaps after craniotomy is a routine part of every
      neurosurgical procedure and there are various options to fixate the bone flap. In
      this paper, we report on a new cranial bone flap fixation d(Cranial Loop)
      implanted in 35 consecutive patients. METHODS: The principle of cranial loop is
      the same as that of a tie rope. With a simple "pull and tighten" movement, the
      device is implanted without the need for additional instruments. The cranial loop
      is made of PEEK [poly(aryl)-ether-ether-ketone] material with the main advantage
      of being artifact free on postoperative imaging. In 35 consecutive patients
      operated by a single surgeon, the cranial loops were used for bone flap fixation.
      All patients had a postoperative CT scanning and a follow-up period of at least 9
      months. RESULTS: In all patients, the bone flap could be easily fixed with 3 or
      more cranial loops without difficulties or material breakage, this within 3 min.
      The postoperative infection rate was 0%, postoperative hemorrhage (either epi/sub
      or intraparenchymatous) requiring reoperation was 0%. None of the patients
      experienced a bone flap dislocation, either clinically or on the postoperative CT
      images. 3D CT-scanning revealed all of the flaps being in a good anatomic
      position. CONCLUSIONS: Although this is a preliminary report in a relatively
      small number of patients, we are of opinion that the cranial loop is a very fast,
      easy, and safe to use bone flap fixation device with the main advantage of the
      absence of artifacts on postoperative CT or MR imaging and lack of cosmetic
      disadvantage.

PMID- 21863520
TI  - Neuronavigation-guided endoscopic management of a pineal region tumour with
      obscured floor of the third ventricle: case report.
AB  - BACKGROUND: Shunt surgery is frequently chosen to manage periventricular
      metastasis of pineal region tumours which obscured the floor of the third
      ventricle. However, this procedure falls short due to distant metastasis.
      Neuronavigation-guided endoscopic surgery offers a viable alternative. PATIENT: A
      17-year-old man became symptomatic from widespread periventricular metastasis of
      a pineal region tumour which completely obscured the floor of the third
      ventricle. RESULTS: Endoscopic tumour biopsy followed by neuronavigation-guided
      endoscopic third ventriculotomy was performed successfully. CONCLUSION: This case
      report emphasizes the value of neuronavigation-guided endoscopic third
      ventriculostomy as a feasible surgical alternative for pineal region tumours with
      widespread periventricular metastasis that obscure the third ventricular floor.

PMID- 21863521
TI  - A ruptured intraorbital ophthalmic artery aneurysm, associated with a dural
      arteriovenous fistula: combined transarterial and transvenous endovascular
      treatment.
AB  - BACKGROUND: True aneurysms of the ophthalmic artery (OA) are extremely rare and
      most often arise at the origin of this artery. We present the endovascular
      management of a ruptured intraorbital OA aneurysm and of an associated dural
      arteriovenous fistula (dAVF). PATIENT: A patient with a ruptured intraorbital
      ophthalmic artery aneurysm, associated with a dAVF with cortical drainage
      presented with acute visual loss and intra- and periorbital hematoma. The
      aneurysm was treated by endovascular coil occlusion. The dAVF was occluded by
      transvenous obliteration of the draining basal vein of Rosenthal. Both
      intraorbital ophthalmic artery aneurysms and their rupture are extremely rare.
      CONCLUSION: Transvenous treatment of dAVFs is well feasible even with very far
      going catheterization, in this case to the origin of the basal vein of Rosenthal.

PMID- 21863522
TI  - FloSeal hemostatic matrix use for intraventricular hemorrhage during a
      neuroendoscopic procedure.
AB  - INTRODUCTION: Neuroendoscopy is a rapidly growing field, but the risk of
      intraventricular hemorrhage is signficant. There are few novel ways of obtaining
      hemostasis for major hemorrhage described in the literature. PATIENT: A 5-year
      old boy with a history of intraventricular hemorrhage and multi-cystic
      hydrocephalus presented with worsening brainstem compression from dilation of a 4
      (th) ventricle cyst. RESULTS: During endoscopic surgery to fenestrate the cyst,
      arterial hemorrhage was emergently controlled with the hemostatic agent, FloSeal.
      CONCLUSION: To the best of the authors' knowledge, this is the first report of a
      patient with intraoperative intraventricular hemorrhage controlled with FloSeal.

PMID- 21863523
TI  - Spontaneous debulking of middle fossa chordoma extension after transnasal
      petroclival biopsy--report of a case.
AB  - BACKGROUND: Clival chordomas are difficult tumors to treat, particularly when
      they have already grown beyond the confines of the clivus. PATIENT: We report the
      case of a 52-year-old man with a clival mass consistent with a chordoma with a
      prominent extension into the right middle fossa. At the patient's request, he
      underwent a simple endonasal biopsy to confirm the diagnosis. A second debulking
      procedure was planned to debulk the remnant tumor. However, follow-up magnetic
      resonance imaging showed that much of the middle fossa tumor had decompressed
      itself through the clival defect into the patient's pharynx. RESULTS: The patient
      underwent additional clival debulking and proton-beam therapy. After 44 months of
      follow-up, he had no clinical or radiographic progression of disease. CONCLUSION:
      It is intriguing to think that leaving a path for easy egress for a chordoma from
      the clivus may prevent it from building up in the bone and spreading.

PMID- 21863524
TI  - Neuroendoscopy combined with intraoperative low-field magnetic imaging for
      treatment of multiloculated hydrocephalus in a 7-month-old infant: technical case
      report.
AB  - BACKGROUND: Treatment of multiloculated hydrocephalus in children remains a
      difficult neurosurgical problem because of the high recurrence rate. Endoscopic
      septostomy with subsequent ventriculoperitoneal shunting is one of the most
      widely accepted therapeutic methods. Intraventricular endoscopic surgery combined
      with intraoperative magnetic resonance (MR) has been used very seldom in infants.
      CASE REPORT: A 7-month-old infant presented with a history of postnatal
      hydrocephalus from the germinal matrix and intraventricular hemorrhage, treated
      with a ventriculoperitoneal shunt. Treatment was complicated by bacterial
      meningitis. On admission the child presented with symptoms of elevated
      intracranial pressure, an MR investigation gave evidence of multiloculated
      hydrocephalus. The patient underwent endoscopic pellucidotomy, followed by
      fenestration of the septa inside the third ventricle, third ventriculostomy and
      aqueductoplasty. Endoscopic navigation was supported by serial intraoperative non
      contrast T1-weighted MR (0.15 T, Polestar N20, Medtronic) images. They also
      served for confirmation of the patency of performed fenestrations and for the
      planning of further steps of the operation. CONCLUSION: Intraoperative low-field
      MR imaging provided an excellent tool for correct navigation of the endoscope
      inside the pathological ventricular compartments and for intraoperative
      assessment of surgical goals.

PMID- 21863525
TI  - Minimally invasive technique for decompression of lumbar foraminal stenosis using
      a spinal microendoscope: technical note.
AB  - BACKGROUND: Lumbar foraminal stenosis is a troublesome disease. Decompression of
      the whole length of the nerve root from the spinal canal to extraforaminal zone
      is often a surgical requirement due to the difficulty in identifying the nerve
      compression site before surgery, making preservation of the posterior elements
      difficult. The authors report a minimally invasive microendoscopic technique for
      lumbar foraminal stenosis to decompress the entire length of the nerve root from
      the spinal canal to the extraforaminal zone while preserving the posterior
      elements. SURGICAL PROCEDURE: A tubular retractor is inserted towards the base of
      the transverse process of the upper vertebra with the retractor tilted inward at
      a 45-degree angle or greater. Approximately one-third of the pedicle is resected
      caudally from the base of the transverse process to the spinal canal. After
      identification of the nerve root, compression factors around the nerve are
      excised from the spinal canal to the extraforaminal zone without damaging
      posterior elements such as the facet joints and pars interarticularis. RESULTS:
      We treated 6 patients with lumbar foraminal stenosis using this procedure. There
      were no complications during the operation, and satisfactory results were
      obtained in all cases. CONCLUSIONS: This microendoscopic technique proved to be
      useful for the treatment of lumbar foraminal stenosis.

PMID- 21863526
TI  - [Iatrogenic late preterm births].

PMID- 21863527
TI  - [Impact of iatrogenic preterm birth on newborn morbidity].
AB  - The incidence of premature births is not decreasing in developed countries, but
      rather shows a tendency to increase. This rise is primarily due to an increase in
      the number iatrogenic late preterm births at a gestational age between 34 + 0 and
      36 + 6 weeks. Late preterm births account for up to 80% of all preterm births and
      these newborns have higher morbidity and mortality rates and a higher rate in
      neurodevelopmental long-term impairment in comparison to term infants. In order
      to reduce iatrogenic preterm birth, it is necessary to apply standardised
      treatment algorithms especially in cases of mild preeclampsia and intrauterine
      growth restriction.

PMID- 21863528
TI  - [Regionalised perinatal care in cases of cervical incompetence and imminent
      premature birth].
AB  - INTRODUCTION: Premature birth due to cervical incompetence is a major obstacle of
      perinatal medicine. While measures of prevention have been investigated, the
      mother should be transferred to a perinatal centre when delivery < 34 + 0 weeks
      is imminent. Delivery in the state of Hessein the large majority of case is
      performed by medically indicated CS: We evaluated the potential prolongation of
      gestation in relation to the level of the institute. METHODS: In order to
      evaluate the influence of the level of the obstetrical institute on the
      prolongation of pregnancy we used the data set of the Hesse perinatal survey
      (HEPE) of the years 1990 - 2009 (n = 449 933). A multivariate analysis excluding
      the confounders prematurity, IUGR,and maternal disease was performed to evaluate
      the relation of prolongation of gestation to the level of care. RESULTS:
      Admissions with imminent premature birth due to cervical incompetence were
      identified in 6 892 cases. Overall prolongation until birth was 9.6 days. When
      the cervical incompetence was < 3 cm the difference between hospitals was not
      significant (12.7 vs. 13.1 d) days. With the cervix >= 3 cm the period after
      admission was merly 0.6 day in level I hospitals - thus significantly lower than
      in perinatal centres (6.5 days). CONCLUSION: In order to achieve optimal
      conditions at birth for very premature newborns the organisation of perinatal
      care should aim at intrauterine transfer to a specialised perinatal unit.A
      precondition is a health system with an adequate structure of perinatal centres
      within 30 k min the case of obstetrical emergencies

PMID- 21863529
TI  - [Respiratory disorders in preterm and term neonates: an update on diagnostics and
      therapy].
AB  - Respiratory disorders remain a major problem in postnatal adaptation. In term
      neonates, an increased incidence of the risk for transient tachypnoea of the
      neonate has been observed during the past decade, most likely secondary to an
      increased usage of primary Caesarean section. The disorder is mainly caused by a
      delayed resorption of foetal lung fluid. Further disorders in term neonates
      include meconium aspiration syndrome and congenital diaphragmatic hernia leading
      to impaired gas exchange and pulmonary hypertension. In preterm neonates,
      respiratory distress syndrome is the main disorder leading to severe acute and
      long-term impaired gas exchange. Prenatal administration of glucocorticoids and
      postnatal surfactant therapy remains an established principle in perinatal care
      for very preterm neonates. The most relevant long-term sequelae, bronchopulmonary
      dysplasia, is currently being observed in about 15% of preterms with less than 32
      weeks of gestation and is associated with severe pulmonary and extrapulmonary
      consequences. Due to the overall improvement in perinatal care, respiratory
      disorders still remain a major problem in pulmonary adaptation. However,
      mortality secondary to neonatal lung failure has been decreased substantially by
      the improvements in the whole field of perinatal medicine.

PMID- 21863530
TI  - [Iatrogenic preterm births and late preterm births of 340/7 to 366/7 - risks and
      chances].
AB  - Late preterm births with a gestational age of 340/7-366/7 are physiologically,
      anatomically and metabolically immature and develop medical complications
      significantly more frequently, have a high morbidity and an elevated mortality.
      Consideration of this knowledge will in future require new strategies for
      obstretric, peripartal and neonatal management options that take into account not
      only maternal risks and demands but also those of the infant.

PMID- 21863531
TI  - On the variability in preterm birth rate, birth weight, and somatic
      classification among neonates of mothers with the same body mass index.
AB  - BACKGROUND: Maternal height and weight are important determinants of perinatal
      outcomes.Height and weight can be combined in the measure of body mass index
      (BMI). We aimed to investigate the utility of maternal BMI as a predictor of
      perinatal outcomes. MATERIALS AND METHODS: Based on data collected between 1995
      and 2000 as part of the German perinatal survey, we examined singleton
      pregnancies of women with BMIs of 18, 24, or 30. We compared preterm birth rate,
      birth weight, and the somatic classification of neonates as small,appropriate, or
      large for gestational age (SGA,AGA, LGA) for women with heights of 150 cm and 180
      cm for each BMI. RESULTS: For women with a BMI of 18 (24; 30)and a height of 150
      cm, the preterm birth rate was 13.9 % (9.1 %; 12.5 %); for women with the same
      BMI and a height of 180 cm the preterm birth rate was 12.1 % (6.1 %; 4.4 %).
      Birth weight for women with a BMI of 18 (24; 30) and a height of 150 cm was 2 889
      g (3 170 g; 3 147 g); for women with the same BMI and a height of 180 cm it was 3
      314 g (3 629 g; 3 753 g). The LGA rate for women with a BMI of 18 (24; 30) and a
      height of 150 cm was 2.1 % (5.2 %; 5.2 %); for women with the same BMI and a
      height of 180 cm it was 7.7 %(20.5 %; 27.7 %). CONCLUSIONS: There is considerable
      variability in perinatal outcomes between women with the same BMI but different
      heights. This limits the utility of BMI as a predictor of perinatal outcomes.

PMID- 21863532
TI  - [Maternal obesity and life-style factors in pregnancy].

PMID- 21863533
TI  - [Comment on the current evaluation of amnioscopy].

PMID- 21863534
TI  - [Current role of MDCT in the diagnosis of coronary artery disease (2011): A
      clinical guideline of the Austrian Societies of Cardiology and Radiology].

PMID- 21863535
TI  - Cardiac MRI: estimation of changes in normalized myocardial gadolinium
      accumulation over time after contrast injection in patients with acute
      myocarditis and healthy volunteers.
AB  - PURPOSE: An increased normalized gadolinium accumulation (NGA) in the myocardium
      during early washout has been used for the diagnosis of acute myocarditis (AM).
      Due to the fact that the pharmacokinetics of contrast agents are complex, time
      related changes in NGA after contrast injection are likely. Because knowledge
      about time-related changes of NGA may improve the diagnostic accuracy of MR, our
      study aimed to estimate the time course of NGA after contrast injection in
      patients as well as in healthy volunteers. MATERIALS AND METHODS: An ECG
      triggered inversion recovery SSFP sequence with incrementally increasing
      inversion times was repetitively acquired over the 15 minutes after injection of
      0.2 Gd-DTPA per kg body weight in a 4-chamber view in 15 patients with AM and 20
      volunteers. The T 1relaxation times and the longitudinal relaxation rates (R1) of
      the myocardium and skeletal musculature were calculated for each point in time
      after contrast injection. The time course of NGA was estimated based on the
      linear relationship between R1 and tissue Gd concentration. RESULTS: NGA
      decreased over time in the form of a negative power function in patients with AM
      and in healthy controls. NGA in AM tended to be higher than in controls (p >
      0.05). CONCLUSION: NGA rapidly changes after contrast injection, which must be
      considered when measuring NGA. Although we observed a trend towards higher NGA
      values in patients with AM with a maximum difference one minute after contrast
      injection, NGA did not allow us to differentiate patients with AM from healthy
      volunteers, because the observed differences did not reach a level of
      significance.

PMID- 21863536
TI  - [Health-economic evaluation of magnetic resonance imaging before biopsy for
      diagnosis of prostate cancer].
AB  - PURPOSE: The aim of this study was the health-economic analysis of MR imaging in
      the diagnostics of suspicious prostate carcinoma (PCa) before execution of a
      first biopsy. MATERIALS AND METHODS: The health-economic analysis included four
      steps: modeling, determination of probabilities, evaluation, and sensitivity
      analyses. We performed an effectiveness analysis from the patient perspective as
      well as a cost-effectiveness and a cost-utility analysis from the health
      insurance perspective for Austria and Germany. The effectiveness and cost
      effectiveness analysis used a hypothetical cohort of 100,000 patients. The result
      parameters were number of biopsies, number of detected PCa, and monetary costs.
      For the cost-efficiency analysis, the result parameters, quality-adjusted life
      years (QALYs) and costs, were calculated for an individual patient. RESULTS: The
      efficiency analysis showed that MRI before a first biopsy can prevent ca. 64,000
      unnecessary biopsies/ 100,000 patients. The diagnostic efficiency was higher by a
      factor of 1.7. Due to MRI, eight PCas were additionally detected. From a health
      insurance perspective, MRI was not cost-effective. Extra costs of ca. 42 m. ? per
      100,000 patients and of 650 ? per prevented biopsy were calculated. The costs per
      detected PCa were increased by 1395 ?. The attainable QALYs were a little higher
      for the MRI alternative, which was therefore not dominated. CONCLUSION: Our
      results do not permit a clear recommendation for or against the application of
      MRI in the diagnostics of PCa. From the patient perspective, it is to be endorsed
      due to the higher medical efficiency. However, it is connected with higher health
      insurance costs.

PMID- 21863537
TI  - [Costs and role of ultrasound follow-up of polytrauma patients after initial
      computed tomography].
AB  - PURPOSE: To assess the costs and diagnostic gain of abdominal ultrasound follow
      up of polytrauma patients initially examined by whole-body computed tomography
      (CT). MATERIALS AND METHODS: A total of 176 patients with suspected multiple
      trauma (126 men, 50 women; age 43.5 +/- 17.4 years) were retrospectively analyzed
      with regard to supplementary and new findings obtained by ultrasound follow-up
      compared with the results of exploratory FAST (focused assessment with sonography
      for trauma) at admission and the findings of whole-body CT. A process model was
      used to document the staff, materials, and total costs of the ultrasound follow
      up examinations. RESULTS: FAST yielded 26 abdominal findings (organ injury and/or
      free intra-abdominal fluid) in 19 patients, while the abdominal scan of whole
      body CT revealed 32 findings in 25 patients. FAST had 81 % sensitivity and 100 %
      specificity. Follow-up ultrasound examinations revealed new findings in 2 of the
      25 patients with abdominal injuries detected with initial CT. In the 151 patients
      without abdominal injuries in the initial CT scan, ultrasound follow-up did not
      yield any supplementary or new findings. The total costs of an ultrasound follow
      up examination were EUR 28.93. The total costs of all follow-up ultrasound
      examinations performed in the study population were EUR 5658.23. CONCLUSION:
      Follow-up abdominal ultrasound yields only a low overall diagnostic gain in
      polytrauma patients in whom initial CT fails to detect any abdominal injuries but
      incurs high personnel expenses for radiological departments.

PMID- 21863538
TI  - [Bezoar of the stomach - a rare differential diagnostic consideration in
      epigastric space occupying lesion of uncertain origin].

PMID- 21863539
TI  - [Unilateral pseudo-Madelung deformity as initial manifestation of Ollier disease
      in a 9-year-old girl].

PMID- 21863540
TI  - Enlargement of the diameter of the peripheral arteries in patients with
      idiopathic venous thrombosis.
AB  - PURPOSE: Recent findings indicate that enlargement of the diameter of the
      peripheral arteries represents a risk of atherosclerotic cardiovascular events.
      As the data indicate a relationship between atherosclerosis and venous thrombosis
      (VT), we investigated whether the diameter of the peripheral arteries is larger
      in patients with idiopathic VT than in healthy subjects. MATERIALS AND METHODS:
      The study included 49 patients with idiopathic VT and 48 age-matched healthy
      controls. Diameters of the brachial, common carotid and common femoral arteries
      as well as the intima media thickness (IMT) of the carotid and femoral arteries
      were measured with the high frequency ultrasound method. RESULTS: Patients had
      significantly higher values for the diameter of the common carotid artery than
      the controls: 7.9 mm (7.4 - 8.4 mm) vs. 7.4 mm (7.0 - 7.9 mm), p < 0.001, and for
      the common femoral artery: 10.3 mm (9.2 - 11.1 mm) vs. 9.5 mm (8.9 - 10.4 mm), p
      = 0.025. Both the carotid and femoral diameters showed significant correlations
      with gender, age, body mass index and IMT. Linear regression analysis confirmed
      that the presence of VT significantly and independently influenced the diameter
      of the carotid and femoral artery but not the brachial artery. CONCLUSION: The
      results of our study showed that carotid and femoral artery diameters are
      enlarged in patients with idiopathic VT in comparison to healthy subjects. Since
      enlargement of the investigated arterial diameters is an indicator of
      atherosclerosis, our findings are consistent with the presumption that there is
      some interrelationship between VT and arterial atherosclerotic disease.

PMID- 21863542
TI  - Finger pulp reconstruction with free dorsoulnar artery perforator (DUAP) flap.
AB  - Finger pulp is a common site for hand injuries, and pulp reconstruction is
      significantly important for optimal handling and sensation. Ideal substitute must
      provide matching texture, tenacity, and slim subcutaneous fat. This article
      presents six cases in which fingertip and finger pulp reconstruction were
      performed via free dorsoulnar artery perforator (DUAP) flap. All flaps survived
      and all patients healed uneventfully without any complications by the end of at
      least 3 months follow-up. Free DUAP flap has proved to be a suitable substitute
      for pulp reconstruction with its thin structure, minimally morbid donor site
      which is also close to the trauma zone, and possibility for neurotization. It can
      be especially favorable when splitting the surgical team for a glabrous flap
      harvest from the foot is not possible.

PMID- 21863543
TI  - An optimized dual-surgeon simultaneous orthotopic hind-limb allotransplantation
      model in rats.
AB  - Composite tissue allograft (CTA) transplantation is a promising treatment in
      reconstructive surgery for complex tissue injuries in humans. However, continued
      research is required to optimize the risk to benefit ratios. In this study, we
      describe, in detail, an optimized simultaneous dual-surgeon orthotopic hind-limb
      transplantation model in direct comparison to a single-surgeon model. In this
      study 75 hind-limb CTAs were performed, employing either a dual-surgeon model (n
      = 60) or a single-surgeon model (n = 15) for the transplantation of two hind
      limbs. Operative times, complication rates, and costs were compared. The dual
      surgeon approach showed a significant reduction of 45.4% in overall operative
      time (p < 0.05). Overall complication rate was 8%. The dual-surgeon model was
      ~30.5% more cost-effective than the traditional single-surgeon approach. Benefits
      of the proposed simultaneous dual-surgeon orthotopic rat hind-limb CTA model
      include decreased operating times, decreased complication rates, and reduced
      financial costs when compared with the established single-surgeon model.

PMID- 21863544
TI  - Microsurgery and telemicrosurgery training: a comparative study.
AB  - Telemicrosurgery (TMS) is a new technique inspired by telesurgery and
      conventional microsurgery (CMS). One of the difficulties of CMS is learning to
      control physiological tremor. TMS eliminates the physiological tremor, thus
      theoretically simplifying microsurgical procedures, but no tactile feedback is
      provided while tying knots. The objective of this study was to assess if the
      learning curve for performing microsurgical anastomosis for TMS than with CMS was
      comparable. Thirty earthworms were anastomosed with 10/0 nylon sutures. In this
      study 15 anastomoses were performed under operating microscope and 15 under Da
      Vinci S(r) robot (Intuitive Surgical, Sunnyvale, CA). A single operator without
      experience in either technique performed all anastomoses. The evaluation
      consisted of measuring the time to perform each stitch, as well as to complete
      the anastomosis. The integrity of the anastomosis was tested by injection of
      saline solution into the earthworm to assess permeability and watertightness. The
      average time to complete a single suture was 296 seconds in the CMS group and 529
      seconds in the TMS group. Permeability and watertightness of anastomosis was
      86.66% in both groups. Learning was faster with CMS than with TMS. For untrained
      surgeon, the absence of tactile feedback is a limiting factor with TMS, however,
      the benefits of the TMS are: three-dimensional high definition vision, abolition
      of physiological tremor, motion scaling of gestures down to 5 times, use of three
      instruments at once, and extreme mobility.

PMID- 21863545
TI  - Autologous alternatives to facial transplantation.
AB  - Advances in autologous reconstructive concepts, principles, and techniques allow
      us to close wounds of almost any size. The concept of three-dimensional (3-D)
      functional units of the face is discussed.  Five cases of facial deformity are
      presented to demonstrate the concept of reconstructing different "functional"
      units of the face with consideration for restoring the 3-D loss of tissue within
      the anatomic boundaries of the aesthetic units. This article demonstrates that
      most individual parts or functional units can be reconstructed with autologous
      techniques in an acceptable way. It is when large segments of multiple contiguous
      functional units are destroyed that these techniques fall short of rebuilding
      parts that function harmoniously with the rest of the face.

PMID- 21863546
TI  - [Repetitive thermal self-manipulation in borderline personality disorder].
AB  - Self-mutilations are one of the major characteristics of patients with borderline
      personality disorder (BPD). Thermal injuries of BPD should be treated by a
      plastic surgeon who is faced to a challenge in the plastic-reconstructive
      strategy because of the most complex psychiatric disease. This means the need of
      a multidisciplinary strategy. Based on 3 case reports such conflict between best
      plastic reconstructive treatment of the burns wound and the psychiatric limit
      with the appropriate therapy options are presented.

PMID- 21863547
TI  - Boning up on mutations: assessing the significance of candidate disease-causing
      DNA sequence variation.

PMID- 21863548
TI  - Interleukin-8 expression associated with canine mammary tumors.
AB  - The use of prognostic markers for mammary cancer is important for routine
      diagnosis and research. Interleukin-8 (IL-8) is a chemotactic cytokine, produced
      by several cell types in response to inflammation. The expression, regulation and
      function of IL-8 in dogs are little known. Recent studies have associated
      angiogenesis and inflammatory processes with tumor malignancy. We investigated a
      possible correlation between IL-8 expression and mammary tumor prognosis in
      female dogs. IL-8 expression was measured in 50 dogs with mammary neoplasia by
      immunohistochemistry and real-time PCR. Immunohistochemical staining was done
      with anti-IL-8 antibodies and PCR amplifications were performed in a 7500 Fast
      Real-Time PCR system. Gene expression stability was analyzed by the geNorm
      software. Quantitative real-time PCR showed that IL-8 expression decreased in
      malignant mammary cells compared to normal mammary tissue, while weak
      immunostaining was associated with a diagnosis of carcinoma. Complementing
      earlier studies on IL-8 expression in several types of cancer, including mammary
      cancer, we conclude that IL-8 has potential for use as a prognostic marker for
      canine mammary neoplasia.

PMID- 21863549
TI  - Gene expression profiling: identification of genes with altered expression in
      Ayu17-449 knockout mice.
AB  - Ayu17-449, a novel gene in mice, has been identified as a tumor-suppressor gene
      in myeloid malignancy; its product catalyzes the conversion of 5-methylcytosine
      of DNA to 5-hydroxymethylcytosine. However, in vivo, its functional target genes
      and biological function have remained unclear. Based on the assumption that
      alterations in the expression of the Ayu17-449 gene affect the expression of
      other related genes, we screened a microarray of altered gene expression in Ayu17
      449(-/-) and Ayu17-449(+/+) mice. We identified 4049 genes with altered
      expression, including 1296 up-regulated (fold change >=2) and 2753 down-regulated
      (fold change <=0.5) genes in knockout mice compared with control mice. We then
      used qRT-PCR and RT-PCR to validate the chip data. Gene ontology and pathway
      analysis were performed on these altered genes. We found that these altered genes
      are functional genes in the complement and coagulation cascades, metabolism,
      biosynthesis, transcriptional regulation, proteolysis, and intracellular
      signaling pathways, such as the peroxisome proliferator-activated-receptor
      signaling pathway, the TNF-alpha-NF-kappaB pathway, the Notch signaling pathway,
      the MAPK signaling pathway, and the insulin signaling pathway. The results of our
      genome-wide comprehensive study could be helpful for comprehending the underlying
      functional mechanisms of the Ayu17-449 gene in mammals.

PMID- 21863550
TI  - Comparison of complete mitochondrial DNA control regions among five Asian
      freshwater turtle species and their phylogenetic relationships.
AB  - The complete mitochondrial DNA (mtDNA) control regions (CR), cytochrome b (Cyt
      b), NADH dehydrogenase subunit 4 (ND4) and cytochrome coxidase subunit I (CO I)
      genes of four Asian freshwater turtles, Mauremys japonica, Ocadia sinensis, M.
      mutica, and Annamemys annamensis, were sequenced using universal PCR and long-PCR
      techniques. Combined with CR sequences of Chinemys reevesii, the composition and
      structure of CR of the five species were compared and analyzed. Three functional
      domains (TAS, CD and CSB) in CR and their conserved sequences (TAS, CSB-F, CSB-1,
      CSB-2, and CSB-3) were identified based on sequence similarity to those of other
      turtles. At the 3' end of CSB, six type motifs of variable number of tandem
      repeats (VNTRs) of five species were recognized, in which the TTATATTA motif may
      be the VNTR motif of the ancestral species of these five turtles. Comparison of
      nucleotide divergences among Cyt b, ND4, CO I, and CR of 11 turtle species using
      transitions + transversions and transversions-only methods supported the
      conclusion that CR evolved 2.6- to 5.7-fold faster than the other mtDNA genes.
      After excluding VNTRs of CR, molecular phylogenetic trees were constructed with
      maximum parsimony, maximum likelihood and Bayesian inference methods. The results
      supported an expanded clade of Mauremys, which included species formerly in
      Ocadia, Chinemys, Mauremys, and Annamemys; this was also reflected in the results
      of VNTR analysis.

PMID- 21863551
TI  - Micronuclei as biomarkers for evaluating the risk of malignant transformation in
      the uterine cervix.
AB  - We evaluated micronucleus and apoptosis occurrence among women with normal smears
      and women with different kinds of cervical abnormalities, i.e., inflammatory
      processes and low- and high-grade squamous intraepithelial lesions (N = 12, N =
      10 and N = 27, respectively). The sample included 59 women who were seen at a
      public medical service for cervical cancer prevention in Feira de Santana, Bahia,
      Brazil. The diagnosis was established by means of cytological, colposcopic, and
      histopathological examination. Cytogenetic analysis was performed on 2000 cells
      from each woman and included assessment of micronuclei and nuclear degenerative
      abnormalities indicative of apoptosis (karyorrhexis, pyknosis and condensed
      chromatin). Micronucleus frequency was significantly higher in the women with
      high-grade squamous intraepithelial lesions than in the women without cervical
      abnormalities or inflammatory processes (P< 0.001) or in the women with low-grade
      squamous intraepithelial lesions (P < 0.005). The frequency of apoptosis was
      similar in women without cervical abnormalities and women showing high-grade
      squamous intraepithelial lesions (P > 0.50), and significantly lower in women
      without cervical abnormalities and in women showing high-grade squamous
      intraepithelial lesions than in women showing inflammatory processes or low-grade
      squamous intraepithelial lesions (P < 0.0001). These results indicate that, in
      addition to Papanicolaou cervical cytological analysis, it would be useful to use
      micronucleus analysis to screen women who are at risk of developing cervical
      cancer. The assessment of nuclear degenerative abnormalities indicative of
      apoptosis increased the sensitivity of this test.

PMID- 21863552
TI  - Polymorphism in Metarhizium anisopliae var. anisopliae (Hypocreales:
      Clavicipitaceae) based on internal transcribed spacer-RFLP, ISSR and intron
      markers.
AB  - Isolates of entomopathogenic fungus Metarhizium anisopliae var. anisopliae were
      characterized using internal transcribed spacer-RFLP, ISSR and intron splice site
      primers. Thirty-seven isolates were studied, most of which were obtained from the
      sugar cane pest, Mahanarva fimbriolata (Hemiptera: Cercopidae) from Tangara da
      Serra, Southwest Mato Grosso State, Brazil. Internal transcribed spacer-RFLP did
      not differentiate the isolates of M. anisopliae var. anisopliae, while ISSR and
      intron primers identified three distinct groups. Variability among these groups
      was 96% for (GTG)(5) and 100% for the other primers. We found considerable
      genetic variability, even among isolates from the same geographical origin and
      host.

PMID- 21863553
TI  - cDNA, genomic sequence cloning and overexpression of ribosomal protein gene L9
      (rpL9) of the giant panda (Ailuropoda melanoleuca).
AB  - The ribosomal protein L9 (RPL9), a component of the large subunit of the
      ribosome, has an unusual structure, comprising two compact globular domains
      connected by an alpha-helix; it interacts with 23 S rRNA. To obtain information
      about rpL9 of Ailuropoda melanoleuca (the giant panda) we designed primers based
      on the known mammalian nucleotide sequence. RT-PCR and PCR strategies were
      employed to isolate cDNA and the rpL9 gene from A. melanoleuca; these were
      sequenced and analyzed. We overexpressed cDNA of the rpL9 gene in Escherichia
      coli BL21. The cloned cDNA fragment was 627 bp in length, containing an open
      reading frame of 579 bp. The deduced protein is composed of 192 amino acids, with
      an estimated molecular mass of 21.86 kDa and an isoelectric point of 10.36. The
      length of the genomic sequence is 3807 bp, including six exons and five introns.
      Based on alignment analysis, rpL9 has high similarity among species; we found 85%
      agreement of DNA and amino acid sequences with the other species that have been
      analyzed. Based on topology predictions, there are two N-glycosylation sites,
      five protein kinase C phosphorylation sites, one casein kinase II phosphorylation
      site, two tyrosine kinase phosphorylation sites, three N-myristoylation sites,
      one amidation site, and one ribosomal protein L6 signature 2 in the L9 protein of
      A. melanoleuca. The rpL9 gene can be readily expressed in E. coli; it fuses with
      the N-terminal GST-tagged protein, giving rise to the accumulation of an expected
      26.51-kDa polypeptide, which is in good agreement with the predicted molecular
      weight. This expression product could be used for purification and further study
      of its function.

PMID- 21863554
TI  - Identification of genes encoding hypothetical proteins in open-reading frame
      expressed sequence tags from mammalian stages of Trypanosoma cruzi.
AB  - Approximately 50% of the predicted protein-coding genes of the Trypanosoma cruzi
      CL Brener strain are annotated as hypothetical or conserved hypothetical
      proteins. To further characterize these genes, we generated 1161 open-reading
      frame expressed sequence tags (ORESTES) from the mammalian stages of the VL10
      human strain. Sequence clustering resulted in 435 clusters, consisting of 339
      singletons and 96 contigs. Significant matches to the T. cruzi predicted gene
      database were found for ~94% contigs and ~69% singletons. These included genes
      encoding surface proteins, known to be intensely expressed in the parasite
      mammalian stages and implicated in host cell invasion and/or immune evasion
      mechanisms. Among 151 contigs and singletons with similarity to predicted
      hypothetical protein-coding genes and conserved hypothetical protein-coding
      genes, 83% showed no match with T. cruzi EST and/or proteome databases. These
      ORESTES are the first experimental evidence that the corresponding genes are in
      fact transcribed. Sequences with no significant match were searched against
      several T. cruzi and National Center for Biotechnology Information non-redundant
      sequence databases. The ORESTES analysis indicated that 124 predicted conserved
      hypothetical protein-coding genes and 27 predicted hypothetical protein-coding
      genes annotated in the CL Brener genome are transcribed in the VL10 mammalian
      stages. Six ORESTES annotated as hypothetical protein-coding genes showing no
      match to EST and/or proteome databases were confirmed by Northern blot in VL10.
      The generation of this set of ORESTES complements the T. cruzi genome annotation
      and suggests new stage-regulated genes encoding hypothetical proteins.

PMID- 21863555
TI  - Methodology: simplified preparation of a DNA ladder using PCR.
AB  - Serving as a DNA molecular weight standard, the DNA ladder has been widely used
      in molecular biology applications. We developed a simple method for the
      preparation of a DNA marker, which involves designing primers to amplify 100- to
      1000-bp DNA fragments using lambda DNA as a template for polymerase chain
      reaction, followed by extraction with phenol/chloroform, precipitation with
      ethanol and mixing. Fragments of 100- to 1000-bp DNA were successfully amplified;
      the sequences showed 100% identity with lambda DNA. This prepared DNA marker
      displayed clear bands, indicating that it can be used for molecular studies.

PMID- 21863556
TI  - Genome wide cloning of maize meiotic recombinase Dmc1 and its functional
      structure through molecular phylogeny.
AB  - The development of meiotic division and associated genetic recombination paved
      the way for evolutionary changes. However, the secondary and tertiary structure
      and functional domains of many of the proteins involved in genetic recombination
      have not been studied in detail. We used the human Dmc1 gene product along with
      secondary and tertiary domain structures of Escherichia coli RecA protein to help
      determine the molecular structure and function of maize Dmc1, which is required
      for synaptonemal complex formation and cell cycle progression. The maize
      recombinase Dmc1 gene was cloned and characterized, using rice Dmc1 cDNA as an
      orthologue. The deduced amino acid sequence was used for elaborating its 3-D
      structure, and functional analysis was made with the CDD software, showing
      significant identity of the Dmc1 gene product in Zea mays with that of Homo
      sapiens. Based on these results, the domains and motives of WalkerA and WalkerB
      as ATP binding sites, a multimer site (BRC) interface, the putative ssDNA binding
      L1 and L2 loops, the putative dsDNA binding helix-hairpin-helix, a polymerization
      motif, the subunit rotation motif, and a small N-terminal domain were proposed
      for maize recombinase Dmc1.

PMID- 21863557
TI  - A new single-nucleotide mutation (rs362719) of the reelin (RELN) gene associated
      with schizophrenia in female Chinese Han.
AB  - Reelin is an extracellular signaling protein that plays an important role in the
      development of the central nervous system. Post-mortem studies have shown lower
      reelin protein levels in the brains of patients with schizophrenia and bipolar
      disorder compared with controls. Genetic studies have also shown that mutations
      in the reelin gene (RELN) increase the risk for schizophrenia and bipolar
      disorder. We evaluated whether an RELN gene variant, rs362719, which has been
      associated with increased susceptibility to bipolar disorder, is also associated
      with susceptibility to schizophrenia. We included 405 Chinese Han schizophrenia
      patients and 390 controls in our study. The polymorphism was genotyped by PCR and
      RFLP methods. We found a significant difference in allele frequency distribution
      (P< 0.05) between schizophrenia patients and controls. The frequency of the A
      allele was significantly higher in schizophrenia patients than in healthy
      controls. The effect of SNP rs362719 on allele distribution was significant in
      female (P < 0.05) but not in male participants (P = 0.473). Besides the gender
      factor, demographic and clinical characteristics of the rs362719 genotype groups
      were also analyzed using the chi-square test, but no significant differences were
      found. We conclude that rs362719 of the RELN gene is associated with
      susceptibility to schizophrenia in Chinese Han, possibly through a gender
      specific mechanism. Further studies will be needed to confirm this genetic risk
      factor for schizophrenia.

PMID- 21863558
TI  - Problems with and a system to eliminate single-primer PCR product contamination
      in simple sequence repeat molecular marker-assisted selection in soybean.
AB  - Polymerase chain reaction (PCR) provides a foundation for simple sequence repeat
      molecular marker-assisted selection (SSR MAS) in soybean. This PCR system and its
      various conditions have been optimized by many researchers. However, current
      research on the optimization of the PCR system focuses on double-primer PCR
      products. We compared single- and double-SSR primer PCR products from 50 soybean
      samples and found that the use of single-PCR primers in the reaction system can
      lead to amplified fragments of portions of the SSR primers in the PCR process,
      resulting in both false-positives and fragment impurity of double-primer PCR
      amplification, inconvenient for subsequent analysis. We used "single-primer PCR
      correction" to eliminate interference caused by single-primer nonspecific PCR
      amplification and improve PCR quality. Using this method, the precision and
      success rates of SSR MAS in soybean can be increased.

PMID- 21863559
TI  - Methodology: a modified method for high-quality DNA extraction for molecular
      analysis in cereal plants.
AB  - Cereal crops that have rigid non-cellulose components in the cell wall tissues of
      leaves and high starch and protein content in grains face limitations in DNA
      extraction. Advanced molecular genetic techniques such as mapping and marker
      assisted selection programs require pure and quick DNA extraction. In this study,
      we developed methods for isolating high-quality genomic DNA from leaves and seeds
      of major cereal crops with minor modifications. DNA yields ranged from 300 to
      1800 ng for 0.01 g seed or leaf tissue.

PMID- 21863560
TI  - Association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a
      Thai population.
AB  - Osteoarthritis is a chronic progressive degenerative joint disease characterized
      by age-related regressive change in articular cartilage. A single nucleotide
      polymorphism has been described at position -174 of the interleukin-6 (IL-6)
      promoter region, leading to three possible genotypes, GG, GC, and CC. We
      investigated a possible association of the IL-6 -174G/C gene polymorphism with
      knee osteoarthritis in a Thai population. Genotype distributions and allelic
      frequencies of the IL-6 -174G/C polymorphism were investigated in 115 knee
      osteoarthritis patients and 100 healthy controls. Genotyping was performed using
      PCR-RFLP. The genotype distribution of IL-6 was 79 GG, 36 GC, 0 CC in knee
      osteoarthritis patients and 88 GG, 12 GC, 0 CC in controls. The frequency of the
      GC genotype in subjects with knee osteoarthritis was higher than in controls (P<
      0.001). Logistic regression analysis showed that the GC genotype was
      independently associated with increased risk of knee osteoarthritis (odds ratio =
      3.3, 95% confidence interval = 1.6-6.9, P = 0.001). These findings suggest that
      the -174G/C polymorphism of the IL-6 gene promoter plays a role in the
      pathogenesis of knee osteoarthritis.

PMID- 21863561
TI  - Molecular characterization of urdbean (Vigna mungo) germplasm related to
      resistance against urdbean leaf crinkle virus.
AB  - Urdbean (Vigna mungo) is an important pulse crop grown worldwide. Urdbean leaf
      crinkle virus (ULCV) is a pathogen of urdbean found in Pakistan that causes huge
      losses in yield. Forty urdbean varieties/lines were screened against the virus
      under field conditions during spring season 2009. None of the lines appeared to
      be highly resistant or resistant. On the basis of a 0-5 disease rating scale and
      disease severity index, genotypes varied significantly in their reaction to ULCV.
      Four lines (M-6206, IAM-382-15, IAM-133, and Mash-1) were moderately resistant,
      eight were rated as moderately susceptible, and 21 as susceptible; the remaining
      seven lines were highly susceptible. RAPD analyses revealed an extensive amount
      of variation, which could be used for cultivar identification. Genetic
      differentiation among urdbean genotypes was similar to the field screening data.
      The varieties 6065-3 and 6206 were highly susceptible and moderately resistant,
      respectively, to ULCV under field conditions, confirmed by the RAPD analysis.
      These varieties were the most diverse varieties in the similarity matrix (67.2%),
      while the varieties IAM-382-9 and 07M003 were the most similar (98.4%). This
      information will help in the recognition of available resistant germplasms that
      can resist this disease and will be utilized for urdbean improvement in Pakistan.

PMID- 21863562
TI  - Single nucleotide polymorphism analysis of exons 3 and 4 of IGF-1 gene in pigs.
AB  - The IGF-1 gene has been implicated as a candidate gene for the regulation of pig
      growth traits. We analyzed exons 3 and 4 of IGF-1 gene polymorphisms of the Banna
      mini-pig (28), the Tibetan mini-pig (30), the Junmu pig (55), and L. Yorkshire
      species (50) using PCR-SSCP. Three genotypes in exon 3 and 6 genotypes in exon 4
      were observed, among which, one single nucleotide polymorphism, G201A, on exon 3
      and two single nucleotide polymorphisms, A440G and T455C, on exon 4 were found.
      Statistical analysis of genotype frequencies revealed that the A allele was
      dominant in the large pig at the G201A locus (PIC = 0.20-0.34), and the AT
      alleles were dominant in the large pig at the A440G and T455C loci (PIC = 0.30
      0.60). The genotype distribution between the various groups was significantly
      different (P< 0.01), with the highest heterozygosity seen in Junmu pigs at 0.223
      and the lowest seen in L. Yorkshire at 0.098. The genetic distance of the Junmu
      pig from the L. Yorkshire is the smallest, the distance from the Tibetan
      miniature pigs is larger, and the distance from the Banna mini-pig is the
      largest. The IGF-1 gene polymorphism and heterozygosity results from various pig
      breeds indicate that IGF-1 is substantially polymorphic with significant
      difference of the polymorphic distribution and expression levels among various
      pig breeds. This information provides a theoretical basis for the genetic
      background of miniature pigs but also provides means to breed improved pig
      varieties.

PMID- 21863563
TI  - Isolation and characterization of 19 polymorphic microsatellite loci from the
      topmouth gudgeon, Pseudorasbora parva.
AB  - The Asiatic topmouth gudgeon, Pseudorasbora parva, is recognized as one of the
      most invasive fish species in many countries outside of Asia. We isolated and
      characterized 19 microsatellite loci from P. parva. The polymorphism of these 19
      loci was tested on 40 individuals of P. parva sampled from a wild population
      located in Ezhou, Hubei province of China. The loci had 5 to 11 alleles, with a
      mean of 7.7 at each locus; 11 loci conformed to Hardy-Weinberg equilibrium. The
      expected and observed heterozygosities ranged from 0.237 to 0.973 and from 0.647
      to 0.914, respectively. All microsatellite loci were in linkage equilibrium.
      These microsatellite markers are potentially useful for the assessment of
      population genetic structure during invasion and dispersal of P. parva in new
      habitats.

PMID- 21863564
TI  - Development and characterization of microsatellite markers for the lizardfish
      known as the Bombay duck, Harpadon nehereus (Synodontidae).
AB  - The Bombay duck, or bummalo (Harpadon nehereus), is a lizardfish native to the
      Arabian sea, but also common in the China sea. It is normally dried and salted
      before consumption and export. To provide molecular information on this
      economically important fish species, we developed and characterized
      microsatellite markers. Ninety positive clones from the (CA)(15)-enriched genomic
      library were sequenced; 62 sequences contained sufficient repeat motifs (di-, tri
      and tetra-nucleotide). Twenty-eight primer pairs were designed and 21 were
      successfully amplified; five loci were polymorphic, but with a low number of
      alleles (three or four). The observed and expected heterozygosities ranged from
      0.3500 to 0.8421 and from 0.5244 to 0.6244, respectively. All of the five
      polymorphic loci were at Hardy-Weinberg equilibrium (adjusted), while linkage
      disequilibrium between Hane-97 and Hane-175 (P< 0.05, adjusted P value = 0.01)
      was significant. The low degree of polymorphism of microsatellite markers may be
      due to the large size of the repeat motifs. These markers will be useful for
      genetic diversity analysis of H. nehereus.

PMID- 21863565
TI  - Application of RNA-seq to reveal the transcript profile in bacteria.
AB  - The large number of microbial genomes deposited in databanks has opened the door
      for in-depth studies of organisms, including post-genomics investigations. Thanks
      to new generation sequencing technology, these studies have made advances that
      have lead to extraordinary discoveries in bacterial transcriptomics. In this
      review, we describe bacterial RNA sequencing studies that use these new
      techniques. We also examined the advantages and biases of these new generation
      technologies; advances in bioinformatics make it possible to overcome the biases,
      providing interesting and surprising results.

PMID- 21863566
TI  - Interleukin-10 promoter polymorphisms associated with susceptibility to lumbar
      disc degeneration in a Chinese cohort.
AB  - We investigated a possible association between interleukin (IL)-10 single
      nucleotide polymorphisms (SNPs) and susceptibility to and severity of lumbar disc
      degeneration (LDD) in a Chinese cohort of 320 patients with LDD and 269 gender-
      and age-matched controls. The degree of disc degeneration was determined by
      magnetic resonance imaging using Schneiderman's classification. Genetic analysis
      of IL-10 promoter polymorphisms (at -1082 A/G, -819 T/C, and -592 A/C) was
      carried out by PCR-RFLP. A total of 134 herniated lumbar intervertebral discs
      were collected during surgery for IL-10 mRNA detection. For SNPs at -592, the A
      allele and AA genotype frequencies were significantly higher in LDD patients than
      in controls. Similarly, the AA genotype and A allele frequencies at -1082 were
      significantly higher in cases than in controls. Among the LDD subjects, carriers
      of AA at -592 and GG at -1082 had significantly lower mean IL-10 mRNA expression
      than the other two genotypes. The SNPs at each locus were not significantly
      associated with severity grade in the LDD patients. Logistic regression analyses
      showed that the AA at -1082, AA at -592, and IL-10 mRNA expression level were
      independent risk factors for LDD. We conclude that the IL-10 SNPs at -1082 A/G
      and -592 A/C as well as IL-10 mRNA in the herniated lumbar intervertebral discs
      are associated with susceptibility to LDD in this Chinese cohort, but not with
      disease severity.

PMID- 21863567
TI  - Meiotic behavior and pollen viability in Moringa oleifera (Moringaceae)
      cultivated in southern Brazil.
AB  - Although originally from India, Moringa oleifera is now cultivated throughout
      most of the tropics, including Brazil. Despite its multipurpose value for food
      and traditional medicine, little is known about the meiotic behavior and pollen
      viability of M. oleifera. We evaluated microsporogenesis and pollen viability in
      eleven plants grown in southern Brazil (Maringa, Parana). Bud flowers were
      collected in different stages of development. All plants that we analyzed
      presented 2n = 28 chromosomes, as previously reported for this species.
      Chromosomes paired as bivalents. Meiotic abnormalities were rare and metaphase I
      was the most affected phase. Pollen viability was superior to 88%. Tripolar
      spindles in metaphase II, leading to the formation of unreduced gametes, were
      recorded in some plants at a low frequency.

PMID- 21863568
TI  - Soybeans as bioreactors for biopharmaceuticals and industrial proteins.
AB  - Plants present various advantages for the production of biomolecules, including
      low risk of contamination with prions, viruses and other pathogens, scalability,
      low production costs, and available agronomical systems. Plants are also
      versatile vehicles for the production of recombinant molecules because they allow
      protein expression in various organs, such as tubers and seeds, which naturally
      accumulate large amounts of protein. Among crop plants, soybean is an excellent
      protein producer. Soybean plants are also a good source of abundant and cheap
      biomass and can be cultivated under controlled greenhouse conditions. Under
      containment, the plant cycle can be manipulated and the final seed yield can be
      maximized for large-scale protein production within a small and controlled area.
      Exploitation of specific regulatory sequences capable of directing and
      accumulating recombinant proteins in protein storage vacuoles in soybean seeds,
      associated with recently developed biological research tools and purification
      systems, has great potential to accelerate preliminary characterization of plant
      derived biopharmaceuticals and industrial macromolecules. This is an important
      step in the development of genetically engineered products that are inexpensive
      and safe for medicinal, food and other uses.

PMID- 21863569
TI  - [Heart valve defects and sports fitness].

PMID- 21863571
TI  - [Syphilis 1923 - 1924 - a contribution from 1924 and comment from the current
      status].

PMID- 21863572
TI  - [CT - diagnosis and differential diagnosis of non-inflammatory acute intestinal
      conditions].
AB  - Multidetector-row CT has shown over the past years that it is able to provide
      reliable diagnoses in various acute intestinal conditions. The presented article
      provides an overview of non-inflammatory acute intestinal pathologies, ranging
      from obstruction to ischemia.

PMID- 21863573
TI  - [CT - diagnosis and differential diagnosis of inflammatory acute intestinal
      conditions].
AB  - Multidetector-row CT has shown over the past years that it is able to provide
      reliable diagnoses in various acute intestinal conditions. The presented article
      provides an overview of primary and secondary inflammatory acute intestinal
      pathologies and their differential diagnoses.

PMID- 21863574
TI  - [Exercise testing and blood pressure].
AB  - Cardiac monitoring with ECG and blood pressure recording is routinely performed
      during a stress test and blood pressure response is an important part of its
      interpretation. Unfortunately, the latter is not straightforward, partly because
      of the inconsistent definition of a pathologic blood pressure response, the
      different populations included in the studies and divergent test modalities. An
      exaggerated blood pressure response in normotensive subjects without coronary
      heart disease is associated with an increased risk of future arterial
      hypertension, whereas in patients with known or suspected coronary heart disease,
      prognosis is not worse than in patients with normal blood pressure response. By
      contrast, exercise induced hypotension, particularly in patients with coronary
      artery disease indicates an increased risk for cardiac events and should be
      investigated further, usually by performing coronary angiography.

PMID- 21863575
TI  - [Frequent exacerbations in chronic obstructive lung disease].

PMID- 21863576
TI  - [Contraindications to beta blockers are eroding more and more - even in COPD].

PMID- 21863577
TI  - [Telemonitoring does not improve outcome of patients with heart failure].

PMID- 21863579
TI  - [CME ECG. Pre-existing heart valve disease].

PMID- 21863582
TI  - Adult learning principles for effective teaching in radiology programmes: a
      review of the literature.
AB  - BACKGROUND: Adult learning processes of acquisition of new knowledge, behaviours,
      skills, values or preferences generally occur as part of personal professional
      development. There is need for radiology residency trainers to understand the
      basic adult learning principles for effective teaching processes. OBJECTIVE: To
      review the different adult learning styles, learning theories and educational
      practice as a guide for radiology residency trainers. METHODS: Literature
      materials from journals, web articles and reputable textbooks in the last 20
      years on adult learning principles in general and radiology in particular were
      reviewed. RESULTS: Most medical educators, including radiologists, lack
      appropriate formal training background in educational practice. The adult
      residency trainee brings to the learning environment high quantity and quality of
      experiences and some amount of control. Connection of this rich adult experience
      base to the learning process requires facilitation and motivation by the
      radiology educator, who must be familiar with the use of appropriate learning
      theories and educational practices. CONCLUSION: there is a general agreement
      about the content of good practice in adult education but a definite
      comprehensive list does not seem to exist in the literature. Nonetheless,
      understanding of the basic adult learning principles would aid the concept of
      guided training, where the adult residency trainee shoulders the bulk of the
      training responsibilities of acquisition of knowledge.

PMID- 21863583
TI  - Assessment and management of severe malnutrition in children.
AB  - BACKGROUND: Severe malnutrition is a common cause of morbidity and mortality
      among children less than five years of age. The World Health Organisation (WHO)
      has developed two manuals for the in-patient treatment of severe malnutrition.
      However, these manuals are not widely distributed with the result that most
      health practitioners caring for severely malnourished children unknowingly use
      practices that, though may be suitable for sick well nourished children, may be
      highly dangerous for the severely malnourished child. OBJECTIVE: This review
      article, based on the two WHO manuals for in-patient treatment of severe
      malnutrition and other relevant literature, seeks to offer the medical fraternity
      the opportunity to abreast themselves with the assessment and case management of
      children with severe malnutrition. CONCLUSION: Health practitioners caring for
      children with severe malnutrition should abreast themselves with the recommended
      guidelines for assessment and management of this common disorder.

PMID- 21863584
TI  - Preventable trauma deaths in Ibadan: a comparison of revised trauma score and
      panel review.
AB  - BACKGROUND: The proportion of preventable trauma-related deaths may be a
      reflection of the quality of trauma care in a health institution. OBJECTIVE: To
      classify mortality in trauma patients in the emergency room and to determine the
      proportion of preventable trauma related mortality in a teaching hospital.
      METHODS: The records of patients who died in the emergency room following trauma
      from January 1996 to December 2005 were reviewed. Data extracted from the
      patients' records included the demographics, the mechanism of injury; and the
      duration of injury prior to presentation. The Probability of Survival (Ps) was
      calculated for each patient using the Revised Trauma Score (RTS). The RTS
      includes three physiologic parameters namely the Glasgow Coma Score [GCS],
      systolic blood pressure and respiratory rate which were recorded soon after the
      patient' presentation at the emergency department. RESULTS: There were 286
      patients who died following trauma from January 1996 to December 2006. There was
      a male: female ratio of 3.4:1. Eighty-one percent were preventable deaths based
      on the revised trauma score while the panel review considered approximately 22%
      as preventable. Fifty-nine percent or 168 of the patients arrived in the hospital
      within six hours of sustaining injury. CONCLUSION: Despite access to emergency
      care within the first six hours (golden hours) the overall survival of our trauma
      patients is poor. The severity of the injuries, inadequate resuscitation, and
      missed injuries by medical personal are some of the factors associated with poor
      outcome of trauma care.

PMID- 21863585
TI  - A clinical review of crossbite in an orthodontic population.
AB  - BACKGROUND: Crossbite is a common occlusal anomaly. It may occur either
      anteriorly or posteriorly and may be either dental or skeletal in origin.
      OBJECTIVE: To determine the pattern and frequency of crossbite occurrence in an
      orthodontic population. METHODS: This was a retrospective study of 633 patients,
      288 males (45.5%) and 345 (54.5%) attending a Lagos orthodontic clinic over a
      five-year period. Information obtained on each patient included age, sex and
      occlusal variables such as overjet, overbite and tooth-bone ratio. RESULTS: Out
      of the 633 patients seen 189 (29.9%) were recorded to have at least one tooth in
      crossbite. Anterior crossbite occurred in 125 (66.1%) of the affected patients
      while posterior crossbite was recorded in 37 (19.6%). Patients presenting with
      anterior and posterior crossbite constituted 27 (14.3%) of patients. Unilateral
      crossbite was slightly more frequently than bilateral crossbite. A total of 445
      teeth were recorded in crossbite with the permanent maxillary lateral incisor
      being the most frequently affected tooth constituting 33.9% of the teeth in
      crossbite. The number of teeth in crossbite per patient ranged from 1 to 8, a
      single tooth in crossbite being most commonly occurring. Crossbite was most
      frequently seen in patients presenting with Class I malocclusion. CONCLUSION:
      Crossbite was a frequently occurring anomaly in the Lagos population, with
      anterior crossbite being more common. There appear to be gender or age difference
      in occurrence of crossbite in our population.

PMID- 21863586
TI  - Diagnostic usefulness of N-terminal pro-brain natriuretic peptide among children
      with heart failure in a tertiary hospital in Lagos, Nigeria.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (NTproBNP) is useful in the
      diagnosis and management of adult patients with heart failure. OBJECTIVE: The
      objective of the study was to determine the usefulness of NT-proBNP in diagnosing
      congestive heart failure (CHF) in children and its correlation with left
      ventricular ejection fraction (LVEF) and clinical heart failure score. METHODS:
      Plasma NT-proBNP was measured in 28 children with CHF and age matched controls.
      Heart failure assessment was done using modified Ross score and all had
      echocardiography done. RESULTS: Mean plasma NT-proBNP of children with CHF
      (377.86+/-1026.49pg/mL) was significantly higher than that of controls (353.61+/
      328.50 pg/mL) (p<0.001). A plasma NT-pro BNP of 951pg/mL was used as the cut off
      value for heart failure. The sensitivity, specificity, negative and positive
      predictive values were 57%, 96%, 69% and 94% respectively. NT-pro BNP levels
      showed a high positive correlation with the modified Ross score (r= 0.502;
      p<0.001) but low correlation with LVEF (r= -0.137; p>0.3). CONCLUSION: Our
      findings indicate that measuring NT-pro BNP may be useful as a diagnostic tool in
      congestive cardiac failure in children. The fact that its levels also correlated
      positively with modified Ross score thereby objectively determining severity of
      heart failure suggests that this biomarker may also be useful as an evaluation
      tool in congestive cardiac failure in children.

PMID- 21863587
TI  - Effect of government-community healthcare co-financing on maternal and child
      healthcare in Nigeria.
AB  - BACKGROUND: Effective maternal and child healthcare delivery requires a proper
      and adequate funding of the health sector. OBJECTIVE: To determine the effect of
      government-community healthcare co-financing on maternal and child healthcare
      services' delivery. METHODS: A descriptive, cross-sectional study with an
      intervention component, conducted amongst 240 women from Igboukwu (intervention
      area), and Ekwuluobia (control area), of Anambra State of Nigeria. RESULTS: The
      biosocial characteristics of the respondents were essentially similar. Better
      utilization of health services occurred in the intervention area post
      intervention. Quality of service from intervention clients' perspective showed
      significant improvement post-intervention. Distance less than five km,
      transportation cost less than N40, and maternal education above secondary level
      impacted positively on utilization of maternal and child health services.
      Acceptability of the scheme was better for the intervention facility evident from
      the higher number of respondents showing "willingness to join", and "willingness
      to pay". CONCLUSION: Health sector funding partnership, positively impacts on
      maternal and child health services. Government's total commitment, backed with
      legislation, and community mobilization, will sustain the scheme.

PMID- 21863588
TI  - Food consumption patterns of female undergraduate students in the United Arab
      Emirates.
AB  - BACKGROUND: Studies on food intake in the UAE especially in relation to the
      student life are lacking. OBJECTIVE: To investigate eating habits of
      undergraduate students. METHODS: A cohort of 146 undergraduate students studying
      Physiology at Zayed University completed a semi-structured questionnaire. A
      student response was accepted for analysis only those weeks with adequate
      responses not more than six. RESULTS: The mean student age was 19.28 (1.22) years
      with a minimum-maximum 18-23 years. The mean weight was 56.67(13.31) with a
      minimum-maximum of 40-89 kg. Of 1,250 United Arab Emirates Dirham; 10 indicated
      they worked but did not specify income; and three were married. More foods were
      consumed seven times in a week. Amongst the principal foods consumed were: bread,
      cereal, starch; white bread, cornflakes and rice; fruits-apple, banana and
      orange; vegetables -cucumber, tomato and lettuce; meat-fish, chicken and beef;
      and eggs and dairy-(milk, cheese and yoghurt). CONCLUSION: Dubai female
      undergraduates have a height intake of milk and fruits and less fanciful breads.
      Further studies should measure the exact quantity/mass of foods consumed per
      week.

PMID- 21863589
TI  - Causes of blindness in a special education school.
AB  - BACKGROUND: Blind children and young adults have to overcome a lifetime of
      emotional, social and economic difficulties. They employ non-vision dependent
      methods for education. OBJECTIVE: To assess the causes of blindness in a special
      school in southwestern Nigeria to aid the development of efficient blindness
      prevention programmes. METHODS: A cross-sectional survey of the Ekiti State
      Special Education School, Nigeria was conducted in May-June 2008 after approval
      from the Ministry of Education. All students in the blind section were examined
      for visual acuity, pen-torch eye examination and dilated fundoscopy in addition
      to taking biodata and history. RESULTS: Thirty blind students with mean age of
      18+/-7.3 years and male: female ratio of 1.7:1 were examined. Blindness resulted
      commonly from cataract eight (26.7%), glaucoma six (20%) retinitis pigmentosa
      four (16.7%) and posttraumatic phthysis bulbi two (6.7%). Blindness was avoidable
      in 18 (61%) of cases. Glaucoma blindness was associated with redness, pain,
      lacrimation and photophobia in 15 (50%) and hyphaema in 16.7% of students; none
      of these students were on any medication at the time of study. CONCLUSION: The
      causes of blindness in rehabilitation school for the blind are largely avoidable
      and glaucoma-blind pupils face additional painful eye related morbidity during
      rehabilitation. While preventive measures and early intervention are needful
      against childhood cataract and glaucoma, regular ophthalmic consultations and
      medications are needed especially for glaucoma blind pupils.

PMID- 21863590
TI  - Clinical and biochemical features of type 2 diabetic patients in Gaza
      Governorate, Gaza Strip.
AB  - BACKGROUND: Diabetes is a multifactorial disease characterized by
      severalmetabolic disorders. Its prevalence rate in Gaza Strip is alarming.
      OBJECTIVE: To describe the clinical and biochemical features of patients with
      Type 2 diabetes in Gaza Governorate. METHODS: Data were obtained through a
      questionnaire interview, patients' records and of 99 type 2 diabetes patients and
      95 healthy individuals. RESULTS: Family history and obesity were risk factors for
      diabetes. The mean age at diagnosis was 41.7+/-8.1 years. Fifty five (55.6%)
      patients had diabetes since 5 years. Distribution of diagnosed diabetic
      complications was low. Micro- and macroalbuminuria in controls and patients (8.4
      v 22.2% and 9.5 v 22.2%, respectively) were associated with diabetes (Chi2 =7.06,
      P=0.007 and (Chi2=5.87, P=0.015, respectively). HbA1c% was significantly higher
      in diabetics (6.93+/-1.22 v 5.36+/-0.57, p<0.001). Serum urea and creatinine were
      significantly decreased in diabetics than controls (mean=23.5+/-6.9 v 27.2+/-7.4
      and 0.49+/-0.15 v 0.58+/-0.14, % differences=13.6 and 15.5, respectively,
      p=0.000). Alkaline phosphatase (ALP) was increased in diabetics (136.9+/-38.7 v
      117.4+/-23.5, % difference =16.6, p=0.001). Cholesterol, triglycerides and low
      density lipoprotein cholesterol (LDLC) were significantly higher in diabetics
      (207.6+/-6.5, 184.1+/-104.5 and 124.6+/-32.9) than controls (181.2+/-39.1,
      139.8+/-76.1 and 102.2+/-37.4) with % differences of 14.6, 31.7 and 21.9%,
      respectively, p<0.001. In contrast, high density lipoprotein cholesterol (HDLC)
      was significantly lower in diabetics (42.6+/-7.8 v 48.2+/-5.7, % difference
      p=11.6 and p<0.001). CONCLUSIONS: Diabetes was associated with family history,
      obesity and micro- or macroalbuminuria. HbA1c%, ALP, cholesterol, triglycerides
      and LDLC were higher in diabetics than controls. In contrast, urea, creatinine
      and HDLC were lower in diabetics.

PMID- 21863591
TI  - Transabdominal chorionic villous sampling in Nigeria: correlation between number
      of cases and other variables.
AB  - BACKGROUND: Transabdominal chorionic villous sampling is generally preferred to
      the transvaginal approach. The procedure may, however, be associated with
      complcations due to a number of factors. OBJECTIVES: To review the relationship
      between the number of cases and other variables in transabdominal chorionic
      villous sampling and also to identify the complications associated with the
      procedure. METHODS: Two hundred and twenty-six cases of transabdominal chorionic
      sampling performed by a single operator were reviewed. Pearson's correlation
      coefficient was used to individually analyze the relationship between numbers of
      samplings performed and other procedure-related variables such as the number of
      needle aspirations, gestational age, percentage diagnosed at first attempt and
      weight of sample. The complications reported during procedure and pregnancy were
      also reviewed. RESULTS: Prenatal diagnosis of sickle cell disease which was
      associated for 95% of the cases was the most frequent (95.1%) indication for
      chorionic villous sampling. There was a statistically significant negative
      correlation between number of cases and needle aspirations (< 0.05) and between
      increasing number of cases and gestational age (>0.05). Also statistically
      significant negative correlations were obtained between number of aspirations and
      weight of sample (r= -0.9, p<0.05) and between gestational age and weight of
      sample (r= -0.89, p<0.05). Correlation between number of cases and weight of
      sample was highly positive (r =+ 0.9). Reported complications included abortion
      and hypertension. CONCLUSIONS: There is a strong relationship between number of
      cases of transabdominal chorionic villous samplings performed and other procedure
      variables.

PMID- 21863592
TI  - Studies on the prevalence of urinary schistosomiasis in Ogun State, South-Western
      Nigeria.
AB  - BACKGROUND: The assessment of the extent and distribution of Schistosoma
      infection in every region in Nigeria is important and required for formulating
      intervention strategies suitable for each endemic area. OBJECTIVE: To assess the
      prevalence of urinary schistosomiasis in Ogun State, South-West Nigeria. METHODS:
      Urine samples of pupils were examined for schistosoma eggs by sedimentation
      technique among selected primary school children. Pretested and structured
      questionnaires were also administered for KAP studies. RESULTS: The overall
      prevalence of 32.2% was observed for schistosomiasis in 276 pupils. Peak
      prevalence of urinary schistosomiasis infection (36.2%) was found in 8-10 years
      age group. Thirty-seven percent reported passing blood in urine, about 50% of
      these informed their parents but 53.1% of the parents did nothing. Contact with
      stream water played a significant role in the transmission of urinary
      schistosomiasis as 80.9% of those infected used the stream water for domestic and
      recreational purposes. There was no significant difference (Chi2 =0.0489, P>0.05
      = 0.0489, P>0.05) between infection status among males and females. CONCLUSION:
      There is need for control measures in this area in order to curb the high
      prevalence of schistosomiasis.

PMID- 21863594
TI  - Issues in blood pressure control among hypertensives attending a specialist
      hypertension service in Jos, Nigeria.

PMID- 21863593
TI  - Human immunodeficiency virus associated with haemophagocytic syndrome in
      pregnancy: a case report.
AB  - BACKGROUND: Haemophagocytic syndrome (HPS) is a rare condition that has been
      documented in association with viral, bacterial, fungal and parasitic infections
      as well as a wide spectrum of malignant neoplasms and autoimmune diseases.
      Whereas HPS is a known cause of anaemia in HIV infection, its occurrence is
      uncommon. Its occurrence in pregnancy is even rarer and very few such cases have
      been reported. METHODS: Full clinical evaluation and investigations including
      bone marrow aspiration cytology were done to elucidate the cause of the anaemia.
      RESULTS: Evaluation revealed severe anaemia, increased serum bilirubin HIV
      positivity and a low CD4 count. The final diagnosis confirmed the case to be
      haemophagocytic syndrome in pregnancy. A 31-year-old primigravida presented at 21
      weeks of gestation with a two-week history of fever, jaundice and abdominal pain.
      She responded to treatment. CONCLUSION: Although a rare condition, this case
      highlights the importance of a high index of suspicion for the syndrome in HIV
      positive pregnant women with persistent Coombs negative haemolytic anaemia. Full
      recovery could be expected following prompt institution of HAART and delivery.

PMID- 21863595
TI  - Abstracts of the 22nd Stroke Society of Australasia Annual Scientific Meeting.
      September 14-16, 2011, Adelaide, South Australia, Australia.

PMID- 21863597
TI  - Bibliography. Anesthesia outside the operating room. Current world literature.

PMID- 21863596
TI  - Reinventing aging through innovation. Abstracts of the International
      Psychogeriatric Association 15th International Congress. September 6-9, 2011. The
      Hague, The Netherlands.

PMID- 21863598
TI  - Effective glycoanalysis with Maackia amurensis lectins requires a clear
      understanding of their binding specificities.

PMID- 21863599
TI  - Poster presentations from the Triological Society's 114th Annual Meeting. April
      29-30, 2011. Chicago, Illinois, USA.

PMID- 21863600
TI  - Abstracts of ESBRA 2011, European Society for Biomedical Research on Alcoholism.
      Vienna, Austria. September 4-7, 2011.

PMID- 21863601
TI  - Abstracts of the Cardiac Society of Australia and New Zealand Annual Scientific
      Meeting and the International Society for Heart Research Australasian Section
      Annual Scientific Meeting. August 11-14, 2011. Perth, Australia.

PMID- 21863602
TI  - Abstracts of the 2011 World Congress on Huntington's Disease. September 11-14,
      2011. Melbourne, Australia.

PMID- 21863603
TI  - Addendum to 'Multiferroic fluorides'.
AB  - An additional eight or ten fluorides with multiferroic phases are listed as an
      addendum to our recent review 'Multiferroic Fluorides' (Scott J F and Blinc R
      2011 J. Phys.: Condens. Matter 23 113202).

PMID- 21863604
TI  - Questionable research conclusions.

PMID- 21863605
TI  - New psychotherapies for mood and anxiety disorders: necessary innovation or waste
      of resources?

PMID- 21863607
TI  - Consequences of SCHIP expansions for household well-being.

PMID- 21863606
TI  - When genetic screening is useful, but not used.
AB  - In families with genetic disorders due to a known genetic mutation,
      presymptomatic genetic testing can lead to early detection and treatment of
      inherited disorders that may manifest later in life. The health benefits for
      family members at increased risk, however, is limited by the predictive value of
      the genetic test, the availability of effective treatments, and individuals' and
      families' willingness to undergo genetic testing in the first place. This Issue
      Brief describes the case of a genetic condition for which genetic screening of
      family members is clearly useful, and just as clearly underused. It explores the
      barriers to the use of genetic screening and has implications for the future as
      genetic technologies become more complex and produce more uncertainty.

PMID- 21863608
TI  - American Board of Family Medicine's Physicians Quality Reporting System registry.

PMID- 21863610
TI  - [A syndrome of chronic pelvic pain].

PMID- 21863611
TI  - Histological effects of zinc and melatonin on rat testes.
AB  - BACKGROUND: The objective of this study is to examine the histological effects of
      zinc and melatonin, alone or in combination, on rat testes. METHODS: For this
      purpose four study groups of ten Sprague-Dawley male rats were formed and treated
      for one month as follows: (1) Controls; (2) Rats injected with 3 mg/kg/day zinc,
      as zinc sulfate; (3) Rats injected with 3 mg/kg/day melatonin and (4) Rats
      injected with 3 mg/kg/day each zinc and melatonin. RESULTS: After four weeks the
      rats treated with melatonin showed inhibited spermatogenesis, testicular tubular
      degeneration and necrosis, obstruction of tubular lumen and lymphocytic
      infiltration. The two zinc-treated groups showed no histological differences to
      controls but the melatonin-only group showed inhibited spermatogenetic activity,
      tubular degeneration and necrosis, as well as obstruction of tubule lumens and
      lymphocytic infiltration. CONCLUSION: The obtained results suggest that 4-week
      treatment with melatonin leads to histological and physiological impairments of
      testis and that zinc supplementation might offset these damaging effects (Tab. 2,
      Fig. 4, Ref. 12).

PMID- 21863612
TI  - Targeting angiogenesis for cancer (gene) therapy.
AB  - Suppression of development of new blood vessels in solid tumors provides a clear
      therapeutic benefit both in experimental animals and human patients. Molecules
      targeting multiple pathways with VEGF pathway being one of the best described are
      currently under consideration to reach use in clinical settings. Even though some
      success has been observed using traditional protein-based inhibitors, alternative
      strategies and new approaches to inhibit excessive tumor angiogenesis are being
      developed and tested. Gene therapy represents a powerful tool for therapeutic
      intervention to angiogenesis. Delivery of genes encoding endogenous angiogenesis
      inhibitors and decoy receptors for proangiogenic factors may bear an advantage
      over classic non-gene therapy in terms of specific targeting, cost-effectiveness
      and safety. Modern approaches focused on gene targeting such as RNA interference
      and microRNA will show the future direction in the field of angiogenesis
      inhibition for cancer treatment (Ref. 68).

PMID- 21863613
TI  - Clinical importance of matrix metalloproteinases.
AB  - This review gives a brief summary on clinical applications of MMPs and their
      determination. Primarily, the activity of MMPs in cancer formation, development
      and metastasis is discussed. Further, survey on methods including fluorimetric
      methods, zymographies, Western-blotting, immunocapture assay, enzyme-linked
      immunosorbent assay, immunocytochemistry and immunohistochemistry, phage display,
      multiple-enzyme/multiple-reagent system, activity profiling, chronopotentiometric
      stripping analysis and imaging methods for detection and determination of MMPs
      follows (Fig. 3, Ref. 100).

PMID- 21863614
TI  - Pharmacogenetics of oral antidiabetic treatment.
AB  - In the majority of patients with type 2 diabetes (T2D), oral antidiabetic drug
      (OAD) treatment is the first line treatment after lifestyle measures fail. Two
      major groups of OAD are used in clinical practice--insulin secretagogues and
      insulin sensitisers. Sulphonyluea (SU) derivatives are insulin secretagogues and
      stimulate insulin secretion by inhibiting ATP-sensitive potassium channels. Genes
      KCNJ11 and ABCC8 encode potassium channel proteins. KCNJ11 gene Glu23Lys
      polymorphism was associated with an increased risk of SU secondary failure, while
      Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU
      drug gliclazide. In addition, the polymorphism of TCF7L2 gene, which has the
      strongest association with T2D, also influenced secondary SU drug failure.
      Insulin sensitisers include both metformin and glitazones. Some drug-genotype
      associations were observed for metformin in patients with T2D. Several genes
      influenced the effect of glitazone treatment. Rosiglitazone was more effective in
      diabetes control in carriers of Prol2Ala polymorphism of PPARG gene encoding the
      PPARg-receptor--the target of this drug. Rosiglitazone treatment had less effect
      on glycemic control and adiponectin increase in T2D patients with GG-genotypes of
      adiponectin (APM1) polymorphism. Pioglitazone treatment had smaller effect on
      glycemic control in patients with LPL Ser447X polymorphism. Identification of
      drug-genotype interactions in pharmacogenetic studies of the OAD treatment might
      have clinical implications in the near future resulting in selection of more
      specific "patient-tailored therapy" in T2D (Tab. 1, Ref. 58).

PMID- 21863615
TI  - Short term oxidative DNA damage by hyperbaric oxygenation in patients with
      chronic leg ulcers.
AB  - INTRODUCTION: Hyperbaric oxygen therapy (HBO) is successfully used for the
      treatment of a variety of conditions and diseases. HBO therapy can be valuable
      for treating selected cases of hypoxic diabetic leg ulcers and chronic venous
      insufficiency. Exposure to high concentration of oxygen is known to induce damage
      to cells, possibly due to an increased oxygen radical production. Reactive oxygen
      species also cause DNA damage. METHOD: The Comet assay method has been used to
      determine DNA damage. Number of DNA strand breaks obtained by the single cell gel
      electrophoresis in nucleuses of lymphocytes was isolated from venous blood.
      Nucleuses of lymphocytes were incubated by bacterial repair endonucleases, which
      detect and remove damaged parts of DNA (SBs, FPG, AlcA, ENDO, and H2O2).
      MATERIAL: 27 patients were investigated in this study; diabetes mellitus was
      diagnosed in 15 of them, and chronic venous insufficiency in 12. They were
      exposed in average 27 times in a hyperbaric chamber to a pressure of 2.5-3ATA of
      100 % oxygen. Lymphocytes were isolated from venous blood before treatment and at
      different time after treatment (24 hours, 7 days, 14 days, 6 weeks). RESULTS AND
      CONCLUSION: Results of DNA damage evaluation at different time periods suggest
      there are no significant changes if compared to initial DNA damage values. HBO
      treatment can be used as adjuvant treatment because no significant risk is
      manifested with this therapy (Tab. 1, Fig. 7, Ref. 52).

PMID- 21863616
TI  - Is carotid endarterectomy under the cervical plexus block safe for all patients
      with various degree of cardiovascular risk?
AB  - BACKGROUND: The result of the GALA study did not answer the question whether it
      is safe to perform carotid endarterectomy (CEA) under the cervical plexus block
      (CPB) in patients at high cardiovascular (CV) risk. The aim of the study was to
      compare CV stability and the frequency of cardiovascular and neurological
      complications in 3 groups of patients with various degree of CV risk who
      underwent CEA under CPB. METHODS: 60 patients operated on in CPB were divided
      into the 3 groups according to the degree of their CV risk (I: very high, II:
      medium, III: low). STATISTICAL ANALYSIS: Chi-square, Kruskal Wallis test.
      RESULTS: No statistically significant difference was confirmed in the changes of
      blood pressure (MAP, BP syst, BP diast), heart rate, cardiovascular
      complications, the rate of the shunt insertion and neurological complications and
      the level of haemodynamic instability, except for hypotension (p = 0.041) in the
      three groups. Life threatening CV complications did not occur in any of the
      groups. The frequency of haemodynamic changes and postoperative complications:
      hypertension (I--40%, II--60%, III--60%), hypotension (I--35%, II--25%, III--5%),
      arrhythmias (I--30%, II--15%, III--10%), neurological complications: 2x (TIA),
      the frequency of shunt insertion: 15 %. CONCLUSION: CPB can be performed in all
      three groups of patients, even in high-risk cardiac patients. The results will
      have to be confirmed in a larger group of patients in future (Tab. 3, Fig. 4,
      Ref. 16).

PMID- 21863617
TI  - Caesarean section in isobaric spinal anesthesia with and without direct
      preoperative hydration with crystalloids.
AB  - BACKGROUND: Because the direct preoperative hydration with crystalloids (20
      ml/kg) does not adequately prevent spinal hypotension during cesarean section,
      the authors investigated whether a continuous intravenous infusion of ephedrine
      (50 mg/500 ml of Ringer solution) without preoperative hydration would prevent
      the spinal hypotension more effectively. METHODS: Forty parturients with ASA
      status I were randomized either to receive a preoperative hydration with 20 ml/kg
      of Ringer solution, or to receive continuous ephedrine infusion, simultaneously
      with spinal anesthesia. The infusion rate was adjusted according to systolic
      blood pressure. Significant hypotension was defined as a systolic blood pressure
      below 100 mmHg. Rescue boluses consisted of ephedrine 10 mg in parturients with
      prehydration and ephedrine 5 mg in parturients with ephedrine infusion. RESULTS:
      Significant hypotension occurred less frequently in the ephedrine group than in
      the volume group: 40% versus 60% (p < 0.05). Nausea and vomiting occurred less
      frequently in the ephedrine group than in the volume group: 40% and 30% versus
      60% and 50%, respectively (p < 0.05). The mean quantity of infused Ringer
      solution was 370 ml +/- 31 in the ephedrine group, i.e. significantly lower than
      1,640 ml +/- 192 in the volume group (p < 0.05). The mean quantity of ephedrine
      given in the ephedrine group was 30 mg +/- 4.1. The mean quantity of ephedrine
      given in the volume group was 25 mg +/- 2. The difference was not significant.
      Apgar scores were similarly good in both groups. CONCLUSION: The continuous
      infusion of ephedrine simultaneously with spinal anesthesia is superior to direct
      preoperative hydration with crystalloids in preventing the spinal hypotension and
      its clinical manifestations in parturients delivered with C-section (Tab. 3, Ref.
      20).

PMID- 21863618
TI  - Portomesenteric vein gas and pneumatosis intestinalis--a rare complication after
      neoadjuvant radiochemotherapy in oesophageal cancer.
AB  - Portomesenteric vein gas and pneumatosis intestinalis is most commonly caused by
      mesenteric ischemia and bowel necrosis but may have a variety of other causes.
      The etiology is multifactorial and the clinical presentation is variable. The
      diagnosis is based on a combination of clinical suspicion and radiographic
      findings. The finding of hepatic portal venous gas alone is not an indication for
      emergent exploration. We report portomesenteric venous gas as a rare complication
      after neoadjuvant radiochemotherapy of the oesophageal cancer (Fig. 3, Ref. 12).

PMID- 21863619
TI  - Orbital melanoma.
AB  - Primary or secondary orbital melanomas are extremely rare tumors; they represent
      less than 1% of primary orbital neoplasms. Over 90% of primary orbital melanomas
      arise from melanocytes (congenital ocular melanosis, oculodermal melanosis). In
      the Department of Ophthalmology, Comenius University, Bratislava, in period 2001
      2007, a total number of 79 patients with uveal melanoma (dg. C69) were treated
      with radical surgery, combined techniques or isolated stereotactic radiosurgery,
      45 (57%) patients with ciliary body and choroidal melanomas were treated with
      primary enucleation, 34 (43%) patients were managed with combined techniques
      (parsplana vitrectomy with endoresection, brachytherapy plus stereotactic
      radiosurgery) or with "conservative treatment", namely with stereotactic
      radiosurgery alone. In group of melanoma patients, primary orbital melanoma was
      present only in 1 case (1 %) (Fig. 4, Ref. 5).

PMID- 21863620
TI  - A forgotten diagnosis in emergency department: tetanus.
AB  - INTRODUCTION: Tetanus is a serious and acute life-threatening disease caused by
      toxins of "Clostridium tetani". Although it is generally a disease of developing
      countries, its lower incidence is encountered also in developed countries. Since
      the principal treatment of this disease is known to be based on vaccination and
      wound care, the emergency physicians play a key role in its management. MATERIAL
      AND METHOD: In the present study, we reviewed its uncommon clinical course along
      with demographic and clinical features of five cases that have presented with
      various complaints to our Emergency Department. Presenting signs, demographic
      features, injury history, and the time from the occurrence of injury to the
      beginning of symptoms were evaluated. RESULTS: Four of five cases were female.
      The mean age of cases was 56.8 (34-73). Three of them had hand injury, one had
      foot injury, and the fifth case had facial injury. The initial symptoms included
      difficult jaw movement, back muscle spasm, and pain. Two cases died. CONCLUSION:
      Tetanus cases may present to ED with different symptoms. Therefore, physicians
      should be aware of the early signs of tetanus. Careful and meticulous wound
      management of cases presented to ED following an injury should be considered a
      significant factor, which can help in reducing the tetanus cases (Tab. 2, Ref.
      18).

PMID- 21863621
TI  - Consequences of abdominal adenocarcinoma in post-menopausal woman in relation to
      surgical and non-surgical management.
AB  - The umbilical tumor as a presenting symptom must be investigated for the
      possibility of metastasis. In this case, it was unlikely, as there was no primary
      carcinoma found elsewhere. Primary peritoneal carcinoma (also termed serous
      surface papillary carcinoma) is a malignancy that arises primarily from
      peritoneal cells. The mesothelium of the peritoneum and the germinal epithelium
      of the ovary arise from the same embryological origin. Although primary
      peritoneal carcinoma has a very poor prognosis, our patient had a disease-free
      interval of two years post surgery. Clinically, primary peritoneal carcinoma may
      be difficult to distinguish from ovarian carcinoma. Compared to ovarian
      carcinoma, primary peritoneal carcinoma has a higher rate of abdominal
      distension, volume of ascites, malignant cells in the ascitic fluid, lower rate
      of pelvic palpable mass, and personal breast cancer history. However, primary
      ovarian cancer can be excluded in this case, based on both ovaries being of
      normal size with no tumor involvement and a histology that favors serous
      carcinoma. The disease is normally disseminated throughout the peritoneum. Our
      patient's disease was confined to the umbilicus with no evidence of
      dissemination. We report a rare case of adenocarcinoma confined to the umbilicus
      of a 64-year-old menopausal woman presented with an umbilical lump of nine years.
      After five years, she presented with a 6-cm irregular periumbilical mass. She
      agreed to undergo an excision biopsy of the mass with total abdominal
      hysterectomy and bilateral salpingo-oopherectomy with omentectomy. The excision
      biopsy showed adenocarcinoma with an appearance suggestive of metastasis from an
      ovarian cystadenocarcinoma. The frozen section of the tumor showed a papillary
      adenocarcinoma. Histology showed adenocarcinoma favoring serous cancer. It was
      found that tumor markers of ovarian malignancy were normal. There was no tumor
      seen in the ovaries, uterus and omentum. On follow-up, there was no disease
      recurrence. The patient has been disease-free for two years post surgery (Fig. 5,
      Ref. 10).

PMID- 21863622
TI  - The topographical features and variations of nervus ischiadicus in human fetuses.
AB  - BACKGROUND: We aimed to investigate the topographical features and variations of
      ischiadic nerve during prenatal period in human. METHODS: Our study was conducted
      on lower extremities of 34 human fetal cadavers who were free of any anomalies
      and were obtained from the department of pathology of our faculty. RESULTS: When
      the development of topographical features of ischiadic nerve is considered
      according to the gestational weeks, it was shown that the distances increased in
      accordance with the age and there was a positive correlation between the two (p <
      0.01), however the width of the ischiadic nerve did not increase similarly and
      there was no significant correlation between its width and the age (p > 0.01).
      CONCLUSIONS: Understanding the structure and course of ischiadic nerve in both
      gluteal and femoral regions is important during all interventions to these
      regions due to the potential damage on the nerve itself. The knowledge of
      topographical features of ischiadic nerve in the prenatal period and its
      relations with reference points that are used especially in childhood and adults
      will help to follow up the variations during postnatal and grow up periods (Tab.
      2, Fig. 4, Ref. 13).

PMID- 21863623
TI  - [Fever with thrombocytopenia associated with a novel bunyavirus in China].

PMID- 21863624
TI  - [Secreted expression of dengue virus type 2 envelope glycoprotein in eukaryotic
      cells].
AB  - OBJECTIVE: To secreted express envelope glycoprotein (E) of dengue virus type 2
      extracellularly. METHODS: The entire prM/E gene was amplified by RT-PCR. An
      optimized signal sequence gene from Japanese encephalits virus (JEV, SA14-14-2
      strain) was introduced using fusion PCR. The impact of E protein transmembrane
      and cytoplasmatic domains was compared by amplifying prM and E with full length
      of E gene, with 20% truncation of the E gene at 3' terminus and one chimeric
      gene, which was generated by replacing the 3' terminal 20% region of E gene with
      the corresponding sequence of JEV (SA14-14-2 strain). The PCR segments were
      inserted into the NheI and NotI sites of pcDNA5/FRT vector or into the NheI and
      XhoI sites of pAcUW51-M. Then they were transfected into 293T cells or Sf9 cells
      respectively. The expression and secretion of E protein were detected by
      immunofluorescence assay (IFA) and Western Blot. RESULTS: After transected into
      293T cells or Sf9 cells, all constructs expressed E protein intracellularly
      indentified by IFA while only two plasmids could secret detectable E protein into
      tissue culture using Western Blot analysis. CONCLUSION: Signal peptide as well as
      the transmembrane and cytoplasmatic domains is crucial for the secretion of
      dengue E protein.

PMID- 21863625
TI  - [Study for association between high risk human papillomavirus and cervical
      lesions in the samples from opportunistic screening].
AB  - OBJECTIVE: To investigate the association between HPV genotypes and cervical
      lesion in Hybrid Capture 2 (HC2) HPV test positive samples. METHODS: 602 cervical
      samples randomly obtained detected as HPV positive by the HC2 high-risk probe
      cocktail were determined by polymerase chain reaction (PCR)-reverse dot blot
      (RDB), among them 344 participated Thinprep Cytology test. RESULTS: 569 (94.5%)
      samples were successfully amplified. The most common HPV genotypes were HPV16
      (31.6%), 52 (16.7%), 58 (15.1%), 56 (8.1%), 39 (7.9%); HPV16 or HPV16/18
      infection was significantly related to ASCUS, LSIL and HSIL; 24 samples suggested
      single HPV infection with the genotypes not available for HC2. CONCLUSION: The
      most common HPV genotypes in random screening were HPV16, 52 and HPV58; Our data
      demonstrated the pseudo-positivity of HC2 test was 4.0%; HPV16 was a index for
      progression of HSIL.

PMID- 21863626
TI  - [The 50% effective dose (ED50a) of seasonal spilt influenza vaccine in mice].
AB  - OBJECTIVE: To evaluate the seasonal influenza spilt vaccine's immunogenicity and
      the 50% effective dose (ED50a) of hemagglutin (HA) that can make 50% of the mice
      hemagglutination inhibition antibody (HI) titers to 40. METHODS: The 2008-2009
      seasonal influenza spilt vaccine's two components, with HA from H1N1 and H3N2
      influenza virus respectively, were used as a model. Mice were immunized once or
      twice with different doses, and the HI antibody titers were tested to determine
      the immunization procedure and to evaluate the immugenicity of seasonal influenza
      spilt vaccine in mice; Consequently, HI antibody response kinetics of the two
      components were observed to determine the time point when the HI antibody titer
      reached the peak point; Finally, mice were immunized with different doses of HA
      to evaluate the ED50a that can make 50% of mice HI titers reach 40. RESULTS:
      Immunization procedures study showed that one-dose of seasonal influenza vaccine
      induced the HI antibody titers ranged from 10 to 120, while two-dose of influenza
      vaccine improved the HI antibody titer 10-100 times as compared with one dose;
      antibody kinetics study suggested that the time point of HI antibody produced to
      peak is 28-35 days post one dose immunization; and the ED50a detection results
      indicated that one dose of 1.5 microg HA could make 50% of the mice HI antibody
      titer reach 40. CONCLUSION: Seasonal influenza spilt vaccine is very immunogenic
      in mouse; the time point of HI antibody produced to peak is 28-35 days post one
      dose immunization; and the ED50a of HA is 1.5 microg, which can make 50% of the
      mice HI titer reach 40. The experimental results provided foundation for the
      establishment of influenza vaccine evaluation system based on seasonal influenza
      vaccine.

PMID- 21863627
TI  - [Bioinformatics analysis of the structure and function correlated to interferon
      sensitivity of HCV core protein].
AB  - OBJECTIVE: To analyze and predict the structure and function correlated to
      interferon sensitivity of HCV Core protein in different genotypes. METHODS: Using
      different bioinformafics software respectively to comparatively analyze and
      predict the secondary structure, tertiary structure, modification site and main
      functional motifs of HCV Core protein. RESULTS: There were diversities in
      secondary structure and tertiary structure of different genotypes. HCV Core
      protein would exist some modification sites about amidation, cAMP, PKC, TYR, and
      interact with amphiphysin SH3 domain, ERK, PKC. CONCLUSION: Differences in
      structure and function of HCV Core protein of different genotypes affected
      interferon sensitivity.

PMID- 21863628
TI  - [The analysis of IL-10 and its methylation in the patients with acute on chronic
      liver failure].
AB  - OBJECTIVE: To investigate the effect of IL-10 and the methylation of its promoter
      in acute on chronic liver failure (ACLF). METHODS: Patients were divided into
      three groups: 25 with ACLF, 25 with CHB, 10 healthy controls. Respectively detect
      the serum level of IL-10 via ELISA, and the methylation of IL-10 promoter via
      MSP, to analyze the difference among the three groups. RESULTS: Both the ACLF
      group and the CHB group have significant increase in serum level of IL-10
      compared with the control group (P < 0.05); the ACLF group's level is higher than
      the CHB group, however without statistical significance (P > 0.05). The serum
      level of IL-10 in ACLF group has no significant relativity with ALT and HBV-DNA(
      r = -0.022, r = 0.033, respectively; P > 0.05); has positive relativity with TBIL
      and MELD ( r = 0.566, r = 0.443, respectively; P < 0.05); and negative relativity
      with PTA (r = -0.581, P < 0.05). The distribution of the methylation of IL-10
      promoter in ACLF group is significantly different from the other two. CONCLUSION:
      The serum level of IL-10 in hepatitis patients is significantly higher and
      increases with the degree of liver failure. The promoter methylation may be
      important in the gene inactivation.

PMID- 21863629
TI  - [Characterization of capsid protein VP3-VP1 genes of hepatitis A virus prevalent
      strains circulated in China].
AB  - OBJECTIVE: To analyse the genetic characteristics of the capsid protein VP3-VP1
      region of hepatitis A virus strains circulated in China. METHODS: The nucleotide
      sequences of VP3-VP1-2A region of 42 HAV IgM positive serum samples were
      sequenced and analysed for nucleotide and amino acid identities and genetic
      characteristics of the VP3-VP1 region. RESULTS: The nucleotide and amino acid
      identities in the VP1-2A junction region among the 42 strains were 89.1% - 100%
      and 97.3% - 100%; while in the complete VP3-VP1 region, the identities were 87.6%
      100% and 98.8%-100%. Strains with identical nucleotide sequences in the VP1-2A
      junction region had 98.4%-100% nucleotide identity in the complete VP3-VP1 region
      and 0-2 amino acid differences in this region. There were no amino acid changes
      at neutralizing antigenetic sites of VP3-VP1 region within the 42 HAV strains.
      CONCLUSION: All the 42 HAV strains belonged to genotype I, with 40 strains
      clustering to sub-genotype IA and 2 to sub-genotype IB. Different HAV strains
      analysed in this paper differed in the nucleotide sequences of the VP3-VP1
      region, but the amino acid sequences were highly conserved with no changes at
      neutralizing antigenetic sites. Both the nucleotide and amino acid sequences of
      the strains with the same VP1-2A junction region were identical or closely
      related when compared in the complete VP3-VP1 region.

PMID- 21863630
TI  - [Research on the aetiology of suspected enterovirus infected patients in Xuzhou
      district in 2009].
AB  - OBJECTIVE: To understand and master the situation in which enterovirus caused
      hand-foot-and-mouth disease (HFMD) in Xuzhou district in 2009 so as to provide
      scientific basis for the control and prevention of hand-foot-and-mouth disease.
      METHODS: The researchers adopted fluorescence RT-PCR method to detect EV and EV71
      as well as the CA16 specificity RNA from 222 samples of anal swabs and
      oropharyngeal swabs from the 240 cases who were diagnosed clinically as hand-foot
      mouth disease infected by enterovirus. Also, the researchers conducted EV71-IgM
      antibody detection on 114 samples of acute phase serum with ELA method. RESULTS:
      Among the 240 enterovirus infected patients, the total EV infection rate is
      72.50% (174/240), among which EV71 infection rate is 57.92% (139/240), CoxA16
      infection rate is 9.17% (22/240), and other EV infection rate is 5.42% (13/240).
      The EV71-RNA positive rate of the samples of 222 anus swabs among the 240
      suspected enterovirus infected patients is 45.94% (102/222), the samples of
      swallow swab EV71-RNA positive rate is 25.68% (57/222) and the EV71-IgM antibody
      positive rate of 114 samples of acute phase serum is 86.84% (99/114). The EV71
      RNA positive rate of oropharyngeal swabs of 254 healthy children is 1.57% (4/254)
      , and no CoxA16-RNA was detected. In the oropharyngeal swabs of 54 close contacts
      (medical personnel), the EV-RNA detected is negative. The positive rate of EV71
      IgM antibody of the 258 healthy children's serum samples is 2.71% (7/258).
      CONCLUSION: The widespreading of hand-foot-mouth disease in Xuzhou district is
      caused mainly by type 71 enterovirus. Inapparent infection of type 71 enterovirus
      exists among children under the age of 3 during the time of widespreading period
      and IgM antibody develops in them. It is difficult for adults to be infected by
      EV71 even if they contact the contagion source closely. The positive rate of EV71
      IgM antibody in the samples of acute phase serum of suspected cases is the
      highest (86.84%), and the second highest is the positive rate of RNA of EV71 of
      anal swabs (45.94%) and of the EV71 of oropharyngeal swabs (25.68%). ELA reagent
      kit is used in the early diagnosis of EV71 infection for it is easy to operate,
      fast and economic, so, it is worth popularizing in the grass-root medical units.

PMID- 21863631
TI  - [Adenoviruses mediated BCL-X1 overexpression protects mice from fulminant hepatic
      failure].
AB  - OBJECTIVE: To indentify the relation between hepatic cells apoptosis and the
      lesion of liver tissue in acute toxic lethal hepatitis. METHODS: 60 Wistar mice
      were randomly divided into normal control, model group and treatment group.
      Normal control and model group were pretreated by portal vein injection of normal
      saline, the treatment group was pretreated by portal vein injection of BCL-X1
      adenoviruses. The mice of model group and treatment group were received an
      injection of D-galn and LPS to establish fulminant hepatic failure models 7 days
      after pretrement. To observe BCL-X1 expression, serum ALT, AST, hepatocyte
      apoptosis rate, and mortality rate of the three groups. RESULTS: The BCL-X1
      expression was higher in treatment group than in model group; 6 hours after
      fulminant hepatic failure models were established,the serum ALT, AST level of
      treatment group was lower than model group;The hepatocyte apoptosis rate of
      treatment group was lower than model group. The death rate of treatment group was
      lower than model group. CONCLUSION: In fulminant mice hepatic failure models, the
      hepatocyte apoptosis rate has a positive correlation with death rate, the
      overexpression of BCL-X1 can decrease the hepatocyte apoptosis rate and the death
      rate.

PMID- 21863632
TI  - [Quantitative analysis of HBV cccDNA from liver biopsy specimens in HBV carriers:
      correlation with serological makers and sera HBV DNA].
AB  - OBJECTIVE: To investigate the correlation of sera HBV DNA and serological makers
      with hepatic tissue HBVcccDNA in chronic HBV carriers. METHODS: Real time
      fluorescence quantitative polymerase chain reaction (RT-PCR) were used to detect
      HBV covalently closed circular DNA (cccDNA) and total intrahepatic HBV DNA from
      30 needle-biopsy specimens as well as HBV DNA in sera in chronic HBV carriers.
      Quantification of the HBsAg, HBeAg in sera were quantified using
      Chemiluminescence immunoassay. RESULTS: HBVcccDNA can be detected in chronic HBV
      carriers, which rang from 3.15 x 10(3) copies/mg to 1.06 x 10(7) copies/mg. There
      was a positive correlation between the cccDNA and HBVtDNA (r = 0.375, P < 0.05),
      but there was no correlation between the cccDNA and sera HBV DNA (P = 0.174).
      There was a positive correlation between cccDNA and sera HBsAg quantification (r
      = 0.562, P < 0.001) but no correlation with sera HBeAg qantification (r = 0.152,
      P > 0.05). CONCLUSION: HBV cccDNA can be replicated stably in hepatic tissue in
      all chronic HBV carriers. HBV DNA in sera can not be indicated hepatic tissue
      cccDNA level. While HBsAg quantification in sera can be used as a marker of
      cccDNA quantification in hepatic tissue to some extent.

PMID- 21863634
TI  - [Construction and identification of attenuated Salmonella which harboring
      enterovirus 71 VP1 gene].
AB  - OBJECTIVE: To develop attenuated Salmonella which harboring enterovirus 71 (EV71)
      VP1 gene. METHODS: The plasmid which expressed VP1 protein of EV71 was
      constructed by gene recombination. Cellular expression was assessed by Western
      Blot analysis. The recombinant plasmid was then transformed into attenuated
      Salmonella SL7207. RESULTS: EV71 VP1 gene sequence was inserted into a eukaryotic
      expression plasmid VR1012. VP1 protein was detected by Western Blot analysis in
      the culture supernatant. And the attenuated Salmonella harbored the plasmid
      stable. CONCLUSION: The plasmid was constructed successfully and it can express
      effectively in vitro. The bacteria which harboring the plasmid were constructed
      successfully. This has provided a basis for further research of an oral EV71
      vaccine.

PMID- 21863633
TI  - [Distribution of hepatitis B virus genotypes and serotypes in people who had a
      physical examination in Yunnan Province].
AB  - OBJECTIVE: To know genotypes and serotypes of hepatitis B virus (HBV) detected
      from hepatitis B infected people in Yunnan Province. METHODS: Serum samples were
      collected from HBsAg carriers detected from people who had a physical examination
      at Yunnan Provincial Center for Disease Control and Prevention. The S genes of
      HBV were amplified by nested PCR and the PCR products were sequenced. The viral
      genotype was identified by phylogenetic analysis. 27 reference sequences
      corresponding to HBV genotype A to I were obtained from GenBank. According to the
      amino acid sequences deduced from the nucleotide sequences of S gene, the
      dominant serotype of HBV detected from these people were confirmed. RESULTS: 39
      HBsAg positive serum samples were detected from 2216 people who had a physical
      examination. The results shows that 76.9% were C genotype; 15.4% were B genotype;
      5.1% were D genotype; 2.5% were I genotype. Three serotypes were found. The rates
      of adw2, adrq+ and ayr serotypes are 71.8%, 17.9% and 10.3% respectively. All of
      adw2 subtype specimens are C genotype. Among the serum specimens in which both
      HBsAg and HBeAg are positive, 75% were C genotype and adw2 subtype. CONCLUSION:
      It is determined that the main genotype and subtype of HBV prevailed in Yunnan
      province is C genotype and adw2 subtype.

PMID- 21863635
TI  - [The study of human rhinovirus in infants with lower respiratory tract
      infections].
AB  - OBJECTIVE: We want to explore the harm degree of human rhinovirus in infants in
      Beijing area. METHODS: From May 2008 to September 2009, 240 nasopharyngeal
      aspirates were collected from the children and infants who were hospitalized and
      with lower respiratory tract infections. These specimens were screened for HRV by
      real-time reverse transcription PCR (RT-PCR) and statistically analysised.
      RESULT: In all of 240 hospitalized children, 208 cases were admission diagnosis
      of pneumonia, accounting for 86.67% (208/240), no deaths, the ratio of male and
      female patients was 1.93 : 1, and the collected samples reached to a maximum
      number in February 2009. Real-time PCR used to detect human rhinovirus, positive
      samples number is 71, positive rate is 29.58% (71/240), and the main symptoms and
      clinical diagnosis was pneumonia. Most cases were less than 2 years old, making
      up 81.69% (58/71), amony them, 13 months-18 months age and > or = 24 months
      groups have the highest incidence rates, the incidence rate is 33.33%.
      CONCLUSION: Human rhinovirus happened in spring and winter seasons, especially
      the infants who were under 2 years are the main infection groups, the important
      symptoms are lower respiratory infections such as pneumonia, bronchitis and
      bronchiolitis et al. Human rhinovirus is seasonal and contagious, spreads fast,
      so protective measures in hospitals should be prepared to avoid cross-infection.

PMID- 21863636
TI  - [One case of correlation between the human herpesvirus 7 DNA load and the hemo
      hagocytic syndrome].
AB  - OBJECTIVE: To research the relationship between human herpesvirus 7 (HHV-7) viral
      Load and the etiopathogenisis of hemophagocytic syndrome, in order to provide
      evidence for the clinical diagnosis of hemophagocytic syndrome and anti-virus
      therapy. METHODS: Peripheral blood of patient with hemophagocytic syndrome during
      different treatment periods, extracted DNA, Syntheticed the primers of HHV-7,
      gene sequence of PCR amplified fragments detected, determined HHV-7 viral Load by
      Real-time fluorescent quantitative PCR and the ferritin concentration in
      peripheral blood detected by chemiluminescence. RESULT: The sequence result
      indicated that PCR amplified fragment was a part of HHV-7 gene, the ferritin
      concentration viried with the load of HHV-7. CONCLUSION: The occurrence of
      hemophagocytic syndrome is connetted with the load of HHV-7.

PMID- 21863637
TI  - [Distribution and clinical significance of HBV genotypes in patients with HBV
      infection in 30 regions of China].
AB  - OBJECTIVE: To explore the distribution and clinical significance of HBV genotypes
      in patients with HBV infection in China. METHOD: Serum samples were collected
      from 2922 patients with HBV infection. HBV genotyping was performed with type
      specific primers polymerase chain reaction, and the virological and biochemical
      markers were detected, which differences in the genotypes distribution between
      various regions and liver function and virological markers between various HBV
      genotyping were analyzed. RESULT: The genotype B, C, B + C, D of 2922 patients
      with HBV infection accounted for 15.9%, 83.5%, 0.41%, 0.21% respectively. In
      Northern China, genotype C was most prevalent, accounting for 90% of all cases,
      while it was less common in Southern China; genotype C was present in Zhejiang
      and Jiangsu provinces, but genotype B was comparatively more common in Guangdong,
      Hunan, Hubei, and Jiangxi provinces. B, C genotype HBV infection patients in the
      sex difference was not statistically significant; B genotypes compared with C
      genotype HBV infection patients, the average age of is less (P < 0.001); HBeAg
      positive rate of C genotype HBV infection patients are higher than that of B
      genotype (P = 0.023); Viral load of genotype C HBV infection patients is higher
      than that of genotype B (P = 0.038); Cholinesterase and Albumin levels of
      genotype C HBV infection patients are lower than that of genotype B (P values
      were 0.016, <0.001). CONCLUSION: There were HBV genotype B, C, B + C and D in
      Chinese patients with HBV infection, with genotype B and C being the major ones.
      Mainly in northern regions of genotype C, C genotype significantly reduced the
      southern region, some of the southern region dominated by B genotype. Genotype C
      HBV infection patients are older, and their HBeAg-positive rate is higher, and
      their liver damage is more severe, but their viral load is less.

PMID- 21863638
TI  - [One-year combination therapy de novo of adefovir dipivoxil and lamivudine for
      decompensated cirrhosis related to HBV].
AB  - OBJECTIVE: To evaluate the efficacy and potential renal impairment of one-year
      combination therapy de novo of adefovir dipivoxil (ADV) and lamivudine (LMV) for
      decompensated cirrhosis related to HBV. METHODS: A total of 36 patients with
      decompensated cirrhosis related to HBV, nobody had nucleos(t)ide analogs (NAs)
      treatment history, were recruited and were divided into two group (control group
      and observation group) randomly. A monotherapy of LMV (100 mg per day) was
      selected to individuals in control group (n = 18), in contrast, a combination
      therapy de novo of ADV (10 mg per day) and LMV (100 mg per day) was applied to
      those in observation group (n = 18). Basic approaches including liver protection,
      symptom-driven intervention, and supporting therapy, were given to all of the
      individuals. A course of one year was applied to all. Liver function, Child-Pugh
      score, serum creatinine (sCr) level, virological response (VR) rate, and
      virological breakthrough rate were observed pro- and post- treatment, differences
      between the two populations were analysed statistically. RESULTS: (1) The
      averages of gender, age, HBeAg status, HBV viral load, sCr level, and Child-Pugh
      score were all compatible in the two groups at baseline (P > 0.05 for all). (2)
      At the endpoint of treatment, none of deaths was reported. Comparing with the
      status before treatment in each group itself, liver function, Child-Pugh score,
      and viral load were improved statistically (P < 0.01 for all), especially in
      observed group (P < 0.01 for all variables, vs control group), as for VR rate,
      result is significant superior to that of control group too (88.89% vs 66.67% , P
      < 0.05). (3) Virological breakthrough occurred to none in observed group and
      three cases (16.67%) in control group, all of them were confirmed to be rtM204V
      variant in the following detection of direct sequencing. (4) Elevated level of
      sCr didn't arised at the end of treatment in two groups. CONCLUSION: Present
      study reveals that in populations with decompensated cirrhosis related to HBV,
      one-year combination therapy de novo of ADV and LMV is superior to monotherapy of
      LMV, and the renal safety is favorable within one year.

PMID- 21863639
TI  - [The levels of HBsAg can predict the efficacy of peglated interferon-alpha 2a
      combined with adefovir dipivoxil, in HBeAg-positive chronic hepatitis B
      patients].
AB  - OBJECTIVE: To investigate the levels of HBsAg in predicting the efficacy of
      peglated interferon-alpha 2a combined with adefovir dipivoxil (ADV), in HBeAg
      positive chronic hepatitis B patients. METHODS: This trial enrolled 62 HBeAg
      positive chronic hepatitis B patients with detectable HBsAg for at least 6 months
      prior to screening, serum HBV DNA levels of at least 100 000 IU/ml. The efficacy
      assessment: viral suppression below 100 IU/ml. The patients with HBV DNA < or =
      100 IU/ml after 24 weeks therapy were divided into group A, in which monotherapy
      continued; While the rest were divided into group B, in which ADV was combined
      until week 48. In group B, at the end-of-treatment, the patients with HBV DNA <
      or = 100 IU/ml were divided into group B1, the rest were divided into group B2.
      RESULTS: There was no significant difference on the baseline characteristics of
      patients between B1 and B2. There was significant difference on the levels of
      HBsAg at 12-week and 24-week between B1 and B2; while there was no significant
      difference on the levels of HBeAg. CONCLUSIONS: The levels of HBsAg at 12-week
      and 24-week would be predictors to evaluate the efficacy of combined therapy in
      HBeAg-positive chronic hepatitis B patients.

PMID- 21863640
TI  - [Epidemiologic and therapeutic status study of patients with hepatitis C].
AB  - OBJECTIVE: To investigate the different infective mode, the time from be
      infectived to be diagnosed and the time from be diagnosed to be treated of
      patients with hepatitis C. METHODS: The different infective mode, the time from
      be infectived to be diagnosed and the time from be diagnosed to be treated of 216
      patients with hepatitis C from march 2004 to march 2009 were retrospectively
      analyzed. RESULTS: 72.22 percents patients suffered from post transfusion
      hepatitis C (PTHC) and 27.78 percents patients suffered from sporadic hepatitisC
      (SHC). 32.61 percents patients were diagnosed after be infectived 15-20 years
      later. 3.26 percents patients were diagnosed after be infectived more than 20
      years later. 33.80 percents patients were treated after be diagnosed more than 5
      years later. 17.13 percents patients were treated after be diagnosed 10-15 years
      later. CONCLUSION: Most patients were infectived with hepatitis C by transfusing
      blood or blood products. Most patients were diagnosed after be infectived more
      than 15 years later. Almost half of patients were treated after be diagnosed more
      than 5 years later, and a significant portion of percents patients were treated
      after be diagnosed more than 10 years later.

PMID- 21863641
TI  - [The analyses of Mycoplasma pneumoniae antibody test results in patients with
      respiratory tract infection].
AB  - OBJECTIVE: To investigate the relationship between the infection rate of
      Mycoplasma pneumoniae (MP) and age, sex and season. METHODS: Passive
      agglutination assay was used to detect Mycoplasma pneumoniae antibodies (MP-Ab)
      in the serum of patients with respiratory tract infection, and MP-Ab test results
      in 2010 were analyzed. RESULTS: The positive rates of 5 year test results were
      30.10%; among the results, the positive rates of male and female patients were
      respectively 30.74% and 36.12%, the difference was statistically significant (P <
      0.05); And every age group were significantly different (P < 0.001), among each
      group, the positive rate of 3-14 years old patients was the highest; the season
      was no significant difference in incidence rates; the patients of positive titer
      > 1:640 accounted for 10.18% of the patients. CONCLUSION: MP infection is
      increasing year by year, children aged 3 to 14 has become the high-risk groups.
      Women are more susceptible to MP than the men and the chances of infection are
      throughout the year, but the most of the patients have a good prognosis.

PMID- 21863642
TI  - [The early diagnosis value of EV 71 IgM class antibodies in the hand, foot and
      mouth disease].
AB  - OBJECTIVE: Assessment of detection of IgM antibodies for human enterovirus 71 (EV
      71) in early diagnosis for the hand, foot and mouth disease (HFMD). METHOD: The
      sera and throat swabs from 38 patients which were clinical diagnosis as HFMD,
      were continuous daily collected in our hospital in 2010. These specimens were
      detected by EV 71 IgM antibodies assay, real time RT-PCR methods for EV 71 and
      Enterovirus. RESULTS: Among 38 HFMD patients, the cumulative positive rates of EV
      71 IgM antibodies were: 60.5% on day 1, 71.1% on day 2, 81.5% in the first 3-4
      days, 92.1% on day 5, 92.1% on day 6, and the positive rate of nucleic acid
      detected by the real time RT-PCR for EV 71 and Enterovirus were 60.5%, 73.6%.
      CONCLUSION: The positive rate of EV 71 IgM antibodies in the hand, foot and mouth
      disease just can occur on day 1, and reach to peak on day 5, which can be used as
      one of indicators of early diagnosis of hand, foot and mouth disease.

PMID- 21863643
TI  - [Application of human papillomavirus dectection in women with abnormal cervical
      cytology].
AB  - OBJECTIVE: To detect the human papillomavirus (HPV) infectious condition in women
      with abnormal cytology and evaluate its values in the screening of high grade
      cervical intraepithelial lesion. METHOD: 101 patients who underwent thinprep cell
      test(TCT) with abnormal cervical cytology were selected to undergo HPV test, all
      subjects also received tissue biopsy at the same time. RESULTS: (1) Among the 101
      patients,the incidence rates of high risk HPV infection of those with ASCUS,
      LSIL, HSIL and squamous cell carcinoma were 84.2%, 88.6%, 100.0% and 2/2
      respectively. (2) Among the patients with abnormal cytology,the number of
      patients with pathologically confirmed results of CIN I and CIN II or worse were
      20 and 81, the incidence rates of high risk HPV infection of those with CIN I and
      CIN II or worse were 60.0% and 97.5% respectively. (3) In the ASCUS group, the
      incidence rates of CIN II or worse with high risk HPV infection were 87.5% and
      the incidence rates of CIN II or worse without high risk HPV infection were
      16.7%. (4) The prevalence of high risk HPV types from highest to lowest order
      were follow: HPV16 (39.6%), 58 (17.8%), 52 (16.8%), 18 (9.9%), 33 (9.9%).
      CONCLUSIONS: The infection rate of high risk HPV was positively correlated with
      the levels of cervical lesions. HPV test is a good triage approach for the
      patients with ASCUS. HPV16, 58, 52, 18, 33 are the most common in the patients of
      cervical lesions.

PMID- 21863644
TI  - [Construction and identification of a vector inserted with gene of T7 RNA
      polymerase].
AB  - OBJECTIVE: To develop a system to rescue virus by intracellular expression of T7
      RNA Polymerase. METHODS: The gene of T7 RNA Polymerase was amplified and cloned
      to VR1012 by molecular biological technology. The expression plasmid VR-1a was
      then identified. VR-1a and EV71 infectious plasmid were co-transfected in Vero
      cell. CPE was observed and viral gene viral antigen were detected. RESULTS: The
      gene of T7 RNA Polymerase was successfully cloned into vector VR1012. Vero cell
      developed to CPE after being transfected VR-1a and EV71 infectious plasmid. EV71
      gene was amplified by RT-PCR from the culture. EV71 antigen was also detected by
      ELISA. CONCLUSION: The method can be used to rescue virus. It could apply to
      immunologic research of EV71 DNA vaccine.

PMID- 21863645
TI  - [High-risk human papilloma virus DNA detection kit (cervista HPV HR) should be
      highly validated clinically in cervical cancer screening programs].
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical significance of High
      risk Human Papilloma virus DNA Detection Kit (Cervista HPV HR) designed to the
      utilized in cervical cancer screening programs. METHODS: The investigation for
      Cervista HPV HR test is designed to detect 437 residual liquid-based cytology
      specimens collected during routine liquid-based Pap tests at standard care vistis
      and to identify the presence of HR HPV. We compared Cervista HPV HR Test against
      standard PCR, in order to examine the performance of Cervista HPV HR Test in
      populations with cervical intraepithelial neoplasia grade 2+ (CIN 2, CIN 3 and
      Cancer, CIN 2+), and the capabilities of A5/A6, A7, A9 oligonucleotides of
      Cervista for predicting CIN2+. RESULTS: The accuracy of Cervista compared to PCR
      with bi-directional sequencing was 88.26%. The positive percent of Cervista HPV
      HR Test and PCR were 38.96% and 29.08%, respectively. The sensitivity,
      specificity, negative predictive value (NPV) and positive predictive value (PPV)
      of Cervista HPV HR Test for the detection of CIN2+ were 98.46%, 58.49%, 99.54%
      and 29.68%, respectively. The A9 oligonucleotides positivity percent was
      significantly higher in CIN2 + (odds ratio: 24.037, 95% CI: 10.086 - 57.283).
      CONCLUSION: The Cervista HPV HR test can be clinically used for detecting HR HPV
      types during routine cervical cancer screening. A9 oligonucleotides were also
      strongly associated with CIN2+ diagnosis, which is improtant in cervical cancer
      screening for triage to colposcopy.

PMID- 21863646
TI  - [The establishment of real time fluorescent PCR detecting method and preliminary
      application on pathogenesis of HFMD].
AB  - OBJECTIVE: To establish the real-time fluorescent PCR method for detecting
      enterovirus, enterovirus 71 and Coxsackievirus A 16 nucleic acid. METHODS:
      Primers and MGB probe were chosen for virus gene. The samples of 38 HFMD patients
      were analyzed by TaqMan-MGB PCR technique on a fluorescence real-time PCR
      instrument,and the results were compared with those by conventional RT-PCR.
      RESULTS: The real-time fluorescent PCR positive rates of EV, EV71 and Cox A16
      were 73.7%, 60.5%, 13.2%; the conventional RT-PCR were 71.1%, 55.3%, 13.2%. There
      were no significant differences between the two methods. CONCLUSION: The real
      time fluorescent PCR detecting method of EV, EV71 and Cox A16 nucleic acid have
      been established successfully.

PMID- 21863647
TI  - Heyde's syndrome: A critical review of the literature.
AB  - Heyde's syndrome is an uncommon association between aortic stenosis and
      gastrointestinal bleeding. Although initially described during the late 1950s,
      with subsequent reports of a possible link between these disorders, controversy
      persists regarding the incidence, pathogenesis, and treatment of this syndrome.
      The main disagreements center on the actual association of aortic stenosis and
      angiodysplasia, though other controversies include the pathogenesis of Heyde's
      syndrome, ranging from von Willebrand factor deficiency and age-related
      degeneration to mucosal ischemia and cholesterol embolization. A variety of
      treatment modalities of the syndrome has been applied, including medical
      management, endoscopic therapy, embolization, and aortic valve replacement. Here,
      the controversies surrounding Heyde's syndrome, which focus on pathogenesis and
      treatment, are reviewed with the aim of providing a clearer understanding of the
      syndrome and the implications for patient care.

PMID- 21863648
TI  - Sound pressure analysis for the early detection of prosthetic valve obstruction.

PMID- 21863649
TI  - In-vitro detection of thrombotic formation on bileaflet mechanical heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: As with all mechanical prostheses, bileaflet
      heart valves are prone to thrombus formation, reduced hemodynamic performance,
      and the occurrence of embolic events. The early detection of thrombotic
      formations is crucial for correct diagnosis and adequate therapy. The study aim
      was to analyze the power spectra of the phonocardiographic signals acquired in
      vitro for various thrombotic deposits reproduced on a bileaflet mechanical valve,
      in order to monitor and classify their presence. METHODS: Data were acquired for
      the St. Jude Medical Regent valve mounted in the aortic position of a Sheffield
      Pulse Duplicator. Different pulsatile flow conditions were reproduced, changing
      the heart rate and stroke volume. Thrombotic deposits of various weights and
      shapes were placed on the valve leaflet, or on the annular housing. The case of a
      thrombus completely blocking one leaflet was also investigated. Power spectra
      were calculated from the phono-cardiographic signals and classified by an
      artificial neural network. RESULTS: The proposed approach resulted in a 95%
      correct identification of all simulated thrombotic deposits. Interestingly,
      phonocardiographic analysis is capable of detecting the presence of different
      types of artificial thrombi and also to classify them, whereas transvalvular
      pressure values cannot provide such detection. CONCLUSION: An effective
      diagnostic tool capable of detecting valvular thrombosis at the early stages of
      formation may help clinicians to formulate valvular dysfunction diagnoses before
      the appearance of critical symptoms. The ability to transfer results obtained in
      vitro to actual clinical situations might represent a significant advance in the
      follow up of patients.

PMID- 21863650
TI  - Individualized thoracic aortic replacement for the aortopathy of biscuspid aortic
      valve disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV) disease is
      associated with an aortopathy resulting in aneurysmal dilatation spanning the
      root, ascending, and arch segments. To date, no large series of proximal aortic
      replacement in this population has been reported. The study aim was to report
      contemporary surgical outcomes for proximal aortic replacement in BAV disease,
      and to examine the relationships between valve morphology, valve pathophysiology,
      and pathology of the thoracic aorta. METHODS: Between September 2005 and December
      2009, a total of 100 consecutive patients (mean age 54 +/- 13 years; range: 29-80
      years) with BAV and proximal aortic enlargement underwent aortic replacement at a
      single referral institution. Of these patients, 16% had undergone prior aortic
      valve replacement (AVR). The aortic repair was individually tailored to treat the
      aortic valve and thoracic aortic pathology, and included supracoronary ascending
      aortic (AA) replacement (n = 17), AVR with separate supracoronary AA replacement
      (n = 39), aortic root replacement (n = 42), and valve-sparing root replacement (n
      = 2). Concomitant arch replacement was performed in 82 patients (80 hemi-arch,
      two full arch). Other concomitant cardiac procedures were performed in 28
      patients. RESULTS: The 30-day/in-hospital rates of death and stroke were both 1%.
      The predominant aortic valve pathophysiology was aortic stenosis (AS; 33%),
      aortic insufficiency (AI; 29%), mixed AS/AI (17%), normally functioning BAV
      (17%), and unknown (4%). Valve morphology included Sievers Type I, R/L (75%),
      Type I, R/N (9%), Type I, L/N (2%), Type 0 (7%), and Type II (7%). BAV patients
      with predominantly AI had more frequent root dilatation (62%) than those with
      either AS (30%) or normal valve function (35%). Based on BAV morphology, there
      were no significant differences in maximal thoracic aortic diameters between
      groups. At a mean follow up of 16 months, there were no late deaths or valve
      related complications. CONCLUSION: Proximal aortic replacement in patients with
      BAV can be performed with low rates of mortality and morbidity. The pathologic
      anatomy of the thoracic aorta was not predicted by the aortic valve morphology,
      although dilation of the aortic root was most common in BAV patients with a
      predominant AI pathophysiology. These findings convey the safety and feasibility
      of treating concomitant aortopathy, including arch replacement as needed, and may
      help tailor the specific operation needed to the patient's pathology.

PMID- 21863651
TI  - Barriers to surgery in severe aortic stenosis patients with Class I indications
      for aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Despite a dismal natural history of severe
      aortic stenosis (AS) in patients with symptoms, there is a high non-surgical
      rate. The study aim was to analyze in detail the decision-making process for
      aortic valve replacement (AVR) that follows the diagnosis of severe AS with Class
      I indications, in order to identify the barriers to surgery. METHODS: A total of
      187 consecutive patients (105 men, 82 women; mean age 74 +/- 14 years) with
      severe AS, defined as aortic valve area (AVA) <1.0 cm2, was evaluated. Detailed
      reviews were performed for patient symptoms, and actions by physicians. The
      sources and reasons for non-surgical management were analyzed. RESULTS: The mean
      AVA was 0.72 +/- 0.19 cm2 and the left ventricular ejection fraction 54 +/- 21%.
      A Class I indication for AVR was present in 174 patients (93%), of whom 125 (72%)
      were referred for AVR, which was performed in 93 cases (53%). The reasons for no
      AVR (n = 81) were patient refusal in 29 cases (36%), comorbidities in 28 (35%),
      while in 19 patients (23%) the AS was considered as 'not severe', despite being
      categorized as severe by ACC/AHA guidelines. The predominant factors in making
      the non-surgical decision were the patient or family (36%), the cardiologist
      (33%), and the surgeon (21%). CONCLUSION: Class I indications for AVR are present
      in most patients with severe AS referred for echocardiography to a tertiary care
      center. Despite a Class I indication, the non-surgical rate remains high and
      attributable to patient reluctance, comorbidities and physician reluctance to
      offer AVR. It is speculated that patient discussions of the dismal natural
      history of severe AS and the major benefit of AVR, preferably conducted within a
      specialized valve clinic set-up, may help to improve the surgical rates.

PMID- 21863652
TI  - Thrombocytopenia following implantation of the stentless biological sorin freedom
      SOLO valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Stentless biological valves have proven
      advantages in hemodynamic performance and left ventricular function compared to
      stented biological valves. Following a marked postoperative fall in the platelet
      count of patients after implantation of the Freedom SOLO valve, the study aim was
      to confirm clinical observations that this effect was more severe in patients
      receiving Freedom SOLO valves than in those receiving St. Jude Medical (SJM)
      mechanical aortic valves. METHODS: Preoperative and postoperative platelet counts
      were compared in two groups of patients who underwent aortic valve replacement
      (AVR) without any concomitant procedures between January and December 2007.
      Patients received either a Freedom SOLO valve (n = 28) or a SJM mechanical valve
      (n = 41). Mean values of platelet counts were compared using three multiple
      linear regression models. RESULTS: Platelet counts were significantly lower in
      the Freedom SOLO group than in the SJM group from the first postoperative day
      (POD 1) up to POD 6 (p <0.001). In three patients of the Freedom SOLO group the
      platelet count fell below 30x10(9)/l, while the lowest level in the SJM group was
      75x10(9)/l. Based on multiple linear regression models, the type of valve
      implanted had a statistically significant influence on postoperative platelet
      counts on POD 1, POD 3, and POD 5 (p <0.001). CONCLUSION: Whilst the reason for
      this phenomenon is unknown, the use of consistent monitoring should prevent
      severe falls in platelet count from becoming dangerous for the patient. Further
      studies are required to investigate the phenomenon since, despite a shorter
      cardiopulmonary bypass time, the fall in platelet count was more profound in the
      Freedom SOLO group.

PMID- 21863653
TI  - Non-resectional repair of myxomatous mitral valve disease: the 'American
      Correction'.
AB  - The 'American Correction', as proposed by Lawrie for myxomatous mitral valve
      disease, utilizes artificial chords and a flexible annuloplasty ring sutured in
      place with a running technique. Leaflet resection is not performed. The aim of
      this review is to describe the physiologic basis of this repair, to contrast it
      with the Carpentier approach, and present the surgical technique in detail.

PMID- 21863654
TI  - Re: Spratt J. Non-resectional repair of myxomatous mitral valve disease: the
      'American Correction'. J Heart Valve Dis 2011;20:407-414.

PMID- 21863655
TI  - Left atrial appendage function in mitral stenosis: is it determined by cardiac
      rhythm?
AB  - BACKGROUND AND AIM OF THE STUDY: The left atrial appendage (LAA) is a common
      source of cardiac thrombus formation associated with systemic embolism in
      patients with mitral stenosis (MS). Low flow velocities in the LAA are important
      factors in the development of thrombosis. Whilst oral anticoagulant therapy is
      used routinely in MS with atrial fibrillation (AF), the characteristics of LAA
      contractile functions and the protective role of oral anticoagulant treatment in
      patients with MS in sinus rhythm (SR) are unclear. The study aim was to compare
      LAA contractile functions in patients with MS who were either in SR or had AF.
      METHODS: The study population comprised 51 patients with MS, who had undergone
      both standard transthoracic and transesophageal echocardiography. The patients
      were allocated to two groups, according to the presence of AF or SR. Ten healthy,
      gender-matched subjects were included in the study as a control group. RESULTS:
      Except for age, the characteristics of the groups were similar. In patients with
      SR and AF, the LAA contractile functions were significantly lower than in
      controls. While the LAA contractile functions of the SR group were significantly
      lower than the AF group (LAA emptying/filling velocity: 26 +/- 7/24 +/- 8 versus
      19 +/- 5/17 +/- 5 cm/s; p = 0.002 and p = 0.001, respectively, LAA
      maximum/minimum area: 5.4 +/- 1.2/3.2 +/- 0.9 versus 6.2 +/- 1.1/3.7 +/- 0.8 cm2,
      p = 0.02 and p =0.02, respectively), no statistically significant differences
      were observed between patients in SR with mitral valve area (MVA) <1.5 cm2 and
      patients in AF. Four SR patients (13%) and six AF patients (27%) had LAA
      thrombus. A strong correlation was observed between the MVA and LAA peak
      emptying/filling velocity in patients with MS in SR (r = 0.739, p = 0.0001 and r
      = 0.728, p = 0.0001, respectively). CONCLUSION: The study results showed that LAA
      contractile function is diminished in patients with moderate-severe MS in SR, and
      to a similar degree as patients in AF. It was concluded that patients with
      moderate-severe MS in SR have a higher risk for thromboembolic events than MS
      patients in AF.

PMID- 21863656
TI  - Reoperations after the ross procedure in adults: towards autograft-sparing/Ross
      reversal.
AB  - BACKGROUND AND AIM OF THE STUDY: The risk of reoperation and loss of a second
      native valve is a major drawback of the Ross operation. The study aim was to
      examine the indications, pathologies, procedures, and outcomes for reoperation
      after the Ross procedure, emphasizing the potential for autograft salvage.
      METHODS: Between 1994 and 2009, a total of 60 reoperations was performed on 55
      patients who previously had undergone the Ross procedure. Attention was focused
      on 49 patients with first-time reoperation for autograft or allograft-related
      problems (37 males, 12 females; mean age 49 +/- 14 years). At the original
      operation, 23% of patients had a history of endocarditis, 14% a previous valve
      replacement, and 61% a bicuspid aortic valve. The original implant technique was
      full root in 88% of cases, inclusion root in 2%, or subcoronary implant in 9%.
      Autograft and aortic indications (n = 38) included root and ascending aorta
      dilatation (53%), structural valve cusp deterioration (32%), endocarditis (11%),
      and technical failure (5%). Regurgitation was moderate to severe in 97% of cases.
      Pulmonary indications (n = 21) were allograft degeneration (71%), endocarditis
      (10%), and Ross reversal (19%). The autograft and aorta reoperation procedures (n
      = 38) included ascending aorta replacement (n = 2), David reimplantation (n = 1),
      valve repair (n = 2), valve replacement (n = 13), and root replacement (n = 22).
      Pulmonary valve replacements (n = 21) were with pulmonary allograft in 12 cases
      and autograft (Ross reversal) in nine. Twelve of the pulmonary valve replacement
      group, including the Ross reversals, were combined aortic and pulmonary. During
      the last 13 reoperations, only two autografts were lost, both of which were
      potentially salvageable. RESULTS: No intraoperative adverse events or
      postoperative deaths occurred, and minimal morbidity was observed. During the
      follow up period there was one death, while two patients required reoperation
      (one for endocarditis and one non-valve-related). CONCLUSION: Reoperation at up
      to 12 years after a Ross procedure was most commonly required for autograft
      failure, and less often for allograft degeneration. Of reassurance to prospective
      Ross patient was the finding that reoperation can be performed safely, and that
      the autograft can be salvaged either by repair and valve-sparing reimplantation
      in the aortic position, or by Ross reversal.

PMID- 21863657
TI  - The CryoLife-O'Brien stentless replacement aortic valve: patterns of valve
      failure.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to describe patterns of
      failure in a consecutive series of patients with the CryoLife-O'Brien stentless
      porcine aortic bioprosthesis. METHODS: The records of patients requiring redo
      surgery were reviewed. All surviving patients were contacted and questioned about
      clinical events since implantation of the valve. RESULTS: The early mortality was
      7%, whilst 4% of patients died between 30 days and one year after surgery, and
      31% died beyond one year. Six cases of structural deterioration were identified;
      five of these cases were due to a cusp tear (usually of the right coronary cusp),
      and one case was due to valve calcification. There were five cases of non
      structural dysfunction; dehiscence was present in three of these cases, with
      progression of minor periprosthetic regurgitation seen immediately after surgery.
      Three failures occurred as a result of infective endocarditis. Structural valve
      deterioration or dehiscence occurred at a mean of 52 months after surgery, with
      no step-up in incidence at any time-point. Primary failure occurred in three of
      49 (6%) bioprostheses manufactured after June 2003, and in eight of 117 (7%)
      manufactured before June 2003. CONCLUSION: The incidence of primary valve failure
      at 52 months after implantation was found to be 7%. It is suggested that routine
      echocardiography be performed at least annually, particularly in those patients
      with even minor paraprosthetic regurgitation on the postoperative study.

PMID- 21863658
TI  - Durability of the Liotta porcine bioprosthesis beyond two decades.
AB  - Porcine valves are generally known to have a limited durability. The case is
      reported of a 35-year-old male patient who underwent mitral valve replacement
      with a 28 mm Liotta porcine bioprosthesis. At reoperation 21 years later, the
      bioprosthesis was replaced (uneventfully) with a second porcine bioprosthesis.
      Pathological and X-radiographic examinations of the excised valve demonstrated
      focal calcification of the leaflets, confirming the long-term durability of the
      Liotta porcine bioprosthesis.

PMID- 21863659
TI  - Prediction of oxygen distribution in aortic valve leaflet considering diffusion
      and convection.
AB  - BACKGROUND: Oxygen supply and transport is an important consideration in the
      development of tissue engineered constructs. Previous studies from our group have
      focused on the effect of tissue thickness on the oxygen diffusion within a three
      dimensional aortic valve leaflet model, and highlighted the necessity for
      additional transport mechanisms such as oxygen convection. The aims of this study
      were to investigate the effect of interstitial fluid flow within the aortic valve
      leaflet, induced by the cyclic loading of the leaflet, on oxygen transport.
      MATERIALS & METHODS: Indentation testing and finite element modelings were
      employed to derive the biphasic properties of the leaflet tissue. The biphasic
      properties were subsequently used in the computational modeling of oxygen
      convection in the leaflet, which was based on the effective interstitial fluid
      velocity and the tissue deformation. Subsequently, the oxygen profile was
      predicted within the valve leaflet model by solving the diffusion and convection
      equation simultaneously utilizing the finite difference method. RESULTS: The
      compression modulus (E) and hydraulic permeability were determined by adapting a
      finite element model to the experimental indentation test on valvular tissue, E =
      0.05MPa, and k =2.0 mm4/Ns. Finite element model of oxygen convection in valvular
      tissue incorporating the predicted biphasic properties was developed and the
      interstitial fluid flow rate was calculated falling in range of 0.025-0.25 mm/s
      depending on the tissue depth. Oxygen distribution within valvular tissue was
      predicted using one-dimensional oxygen diffusion model taking into consider the
      interstitial fluid effect. It was found that convection did enhance the oxygen
      transport in valvular tissue by up to 68% increase in the minimum oxygen tension
      within the tissue, depending on the strain level of the tissue as reaction of the
      magnitude and frequencies of the cardiac loading. CONCLUSIONS: The effective
      interstitial fluid velocity was found to play an important role in enhancing the
      oxygen transport within the valve leaflet. Such an understanding is important in
      the development of valvular tissue engineered constructs.

PMID- 21863661
TI  - 'Clover technique' for tricuspid regurgitation due to pacemaker lead.
AB  - Whilst tricuspid regurgitation (TR) secondary to severe mitral regurgitation (MR)
      is a common problem, organic TR caused by pacemaker leads is also frequently
      encountered. In a 63-year-old patient who developed TR attributable to both MR
      and a pacemaker lead inserted 12 years previously, the regurgitation could not be
      controlled satisfactorily using a normal ring annuloplasty. Consequently, the
      'clover technique' provided an efficient correction to the TR.

PMID- 21863660
TI  - Can valvular interstitial cells become true osteoblasts? A side-by-side
      comparison.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve calcification is believed to
      involve the differentiation of valvular interstitial cells (VICs) into either a
      myofibroblastic or an osteoblast-like phenotype. Despite purported similarities
      between diseased VICs and osteoblasts, few studies have directly compared VICs
      and osteoblasts in side-by-side experiments. In the present study, VICs were
      compared against multiple osteoblastic cell types at different stages of
      differentiation. These findings may help to resolve whether VICs progress through
      a myofibroblastic phenotype before reaching an osteoblast-like stage. METHODS:
      Three cell types representing a range of osteoblastic lineage commitment and
      differentiation were used in the phenotypic comparison against VICs.
      Specifically, VICs, embryonic fibroblasts (C3H10T1/2), pre-osteoblasts (MC3T3
      E1), and mature primary osteoblasts were cultured on tissue-culture polystyrene
      in control or mineralization medium, and harvested for qPCR, DNA, and protein
      analysis at time points ranging from one to eight days. RESULTS: Culture of VICs
      in mineralization medium decreased the expression of alpha-smooth muscle actin
      (alpha-SMA; a myofibroblast marker), with no peak in alpha-SMA gene or protein
      expression in mineralization medium at any time point. The application of a
      mineralization medium led to increased expression levels of alkaline phosphatase
      (ALP; an early mineralization marker) for all cell types, although the magnitude
      of the increase in ALP was drastically smaller for VICs than for the osteogenic
      cell types. Only the osteogenic cell types demonstrated an appreciable increase
      in osteocalcin (an indicator of later-stage mineralization). CONCLUSION: While
      the addition of mineralization medium generally increased the expression of
      osteogenic markers and decreased the expression of myofibroblastic markers, VICs
      displayed different levels and patterns of expression than the osteoblastic cell
      types used for comparison. Additionally, the lack of an alpha-SMA increase at any
      point after the addition of mineralization medium to VICs indicated that these
      cells may not need to progress through a myofibroblastic stage before reaching an
      osteoblast-like gene expression profile.

PMID- 21863662
TI  - Side-wire technique for percutaneous pulmonary balloon valvuloplasty.
AB  - On occasion during percutaneous pulmonary balloon valvuloplasty, a small balloon
      may slip into the pulmonary artery when dilating a stenotic pulmonary valve. In
      order to stabilize the balloon should a larger balloon size not be available, a
      side wire can be used without changing the original balloon.

PMID- 21863663
TI  - Infective endocarditis presenting with ST segment elevation.
AB  - Despite diagnostic and therapeutic advances, mortality and morbidity associated
      with infective endocarditis (IE) remains high. Congestive heart failure and
      complications such as septic embolization and aortic root abscess are the main
      causes. Although aortic root abscess is a common complication of IE involving the
      aortic valve, acute myocardial infarction (AMI) is a rare complication in
      patients with endocarditis, whether in the acute or later phase of infection. In
      most cases, the infarction is either anterior or anterolateral. To the best of
      the present authors' knowledge, only one case of infarction at a purely inferior
      site has been reported previously. In the present case, IE with an aortic root
      abscess presented clinically as an acute inferior wall myocardial infarction.

PMID- 21863664
TI  - Left ventricular dysfunction mimicking Takotsubo cardiomyopathy following cardiac
      surgery.
AB  - Left ventricular dysfunction with apical ballooning consistent with Takotsubo
      cardiomyopathy was encountered in a 68-year-old woman at 5 h after an uneventful
      mitral valve replacement and tricuspid valve repair. Preoperatively, the patient
      had emotional stress as well as worsening congestive heart failure, which might
      have contributed to this rare postoperative complication. Following diagnosis by
      transthoracic echocardiography (TTE), and characteristic findings of apical
      ballooning and a preserved basal contraction of the left ventricle, intra-aortic
      balloon pumping (IABP) was initiated to minimize the use of inotropic drugs. The
      patient was successfully weaned from both the IABP and pharmacological support.
      Follow up with serial TTE showed a gradual recovery of the left ventricle to
      normal systolic function. The mechanism of onset and pathophysiology of Takotsubo
      cardiomyopathy remain unclear, especially in postoperative cardiac surgery
      patients. Since excessive catecholamine stimulation has been proposed as a
      possible mechanism of Takotsubo cardiomyopathy, early mechanical circulatory
      assistance after cardiac surgery is advised to minimize catecholamine use in this
      rare complication.

PMID- 21863665
TI  - Disc wear and entrapment in a Starr-Edwards mitral caged-disc valve.
AB  - A case of wear and entrapment of a polyethylene disc observed in a Starr-Edwards
      (SE) mitral caged-disc valve at 37 years after implantation is reported. A 66
      year-old woman who had undergone mitral valve replacement with a SE disc valve 37
      years previously was admitted to the authors' hospital. Cinefluoroscopy showed
      the polyethylene disc of the SE valve to have impinged against a calcified mass
      on the left ventricular posterior wall, causing a tipping motion of the disc
      during opening. The valve was successfully replaced at surgery. A macroscopic
      examination of the excised valve revealed wear of the polyethylene disc at sites
      where the disc abutted the cage struts, and where it impinged on the calcified
      mass. The long-term durability of the SE caged-disc valves has been favorable;
      however, when implanted for over 20 years, they should be carefully followed up.

PMID- 21863666
TI  - Prolonged anticoagulation with fondaparinux for mechanical cardiac valves in the
      setting of intracranial hemorrhage.

PMID- 21863667
TI  - Beta-blocker for severe aortic regurgitation?

PMID- 21863668
TI  - Pulmonary artery aneurysm.

PMID- 21863669
TI  - Outcomes of pregnancy termination by misoprostol at 14-32 weeks of gestation: a
      10-year-experience.
AB  - OBJECTIVE: To review outcomes of pregnancy termination between 14-32 weeks of
      gestation based on a 10-year-experience of misoprostol use at Maharaj Nakorn
      Chiang Mai Hospital. STUDY DESIGN: A retrospective, descriptive study MATERIAL
      AND METHOD: Based on the authors' prospective database, all pregnancy
      terminations by misoprostol between 14-32 weeks of gestation between 1998 and
      2008 were reviewed. The main outcomes included success rate of termination, mean
      induction-to-abortion time, and complication rate. In addition, regimens and
      routes of drug administration as well as indications for termination of pregnancy
      were also analyzed. RESULTS: Seven hundred forty one pregnancy terminations were
      performed using misoprostol with dosage varied from 50 mcg to 800 mcg, mostly 400
      mcg intravagina every three hours. The most common indication for pregnancy
      termination was severe fetal thalassemia (35.8%). The majority of cases were
      pregnancies with live fetuses and only 18.2% were associated with a dead fetus in
      utero. Success rate of termination within 48 hours was 85.9%. Pregnancies with
      previous cesarean section accounted for 8.6% of cases. The mean gestational age
      was 20.94 weeks. The mean abortion time was 25.35 hours, ranging from 1.25 to
      247.88 hours. The two most common adverse effects were chill and fever (43.7% and
      34.3%). The rate of analgesia needed was 39.3%. No serious adverse complications
      such as uterine rupture were found CONCLUSION: This experience suggests that
      misoprostol has a high efficacy for pregnancy termination with acceptable minor
      side effects and it is relatively safe when used with precaution.

PMID- 21863670
TI  - Quality of life among Thai women diagnosed with cervical cancer and cervical
      intraepithelial neoplasia at King Chulalongkorn Memorial Hospital.
AB  - OBJECTIVE: To determine health related quality of life (QoL) of patients
      diagnosed with cervical intraepithelial neoplasia (CIN) and cervical cancer
      compared QoL among stages of cancer and to study the association between QoL and
      patients' characteristics. MATERIAL AND METHOD: The questionnaire elicited
      information and QoL using Functional Assessment of Cancer Therapy General (FACT
      G) questionnaire. The study population was patients with a diagnosis of one of
      the four FIGO stages of cervical cancer RESULTS: One hundred seventy two patients
      completed the present study. The adjusted mean scores QoL was 78.76. There were
      no significant differences between FIGO stages on the global QoL and subscale.
      The authors found negative association between age and physical wellbeing scores
      (p = 0.049) and a positive association between age and emotional wellbeing scores
      (p = 0.004). Lower educational attainment was associated with higher emotional
      wellbeing scores (p = 0.004). CONCLUSION: For many patients, family, religion, or
      psycho-social support may be considered a necessity. The younger and better
      educated groups may require more information and psycho-emotional support.

PMID- 21863671
TI  - A novel influenza A H1N1 clinical manifestations in patients at Chiang Mai
      University Hospital.
AB  - OBJECTIVE: To describe the clinical manifestations of patients affected with a
      novel influenza A (H1N1 2009) during the pandemic. MATERIAL AND METHOD: A
      retrospective study was conducted in patients with influenza-like illness
      receiving care at Chiang Mai University Hospital between June 1 and September 30,
      2009. The inclusion criteria were as follows 1) patients had influenza-like
      illness that was defined as fever, with cough and/or sore throat, 2) detection of
      influenza A H1N1 2009 by real-time polymerase chain reaction (RT-PCR) from
      nasopharyngeal swabs or throat swabs. RESULTS: Among 278 patients, 150 patients
      (54.0%) were male and the mean age was 21.4 +/- 13.1 years (range 1-74). Eighty
      seven patients (31.3%) were in age group 15-19 years. Fifty-eight patients
      (20.9%) had underlying diseases and asthma was the most common health problem.
      The presenting symptoms were cough (dry or productive) (248 patients, 89.2%),
      fever > or = 38.0 degrees C (229 patients, 82.4%), sore throat (195 patients,
      70.1%), rhinorrhea (126 patients, 45.3%) and myalgia (113 patients, 40.6%). Five
      patients had co-infection at admission, three patients had dengue hemorrhagic
      fever, one patient had mycoplasma infection, and the other one with Acinetobacter
      lwoffi bacteremia. One hundred forty four patients (51.8%) received oseltamivir.
      Two hundred seventy two patients (97.8%) recovered without complications. One
      pregnant-woman developed severe pre-eclampsia five days after the first symptom,
      one patient developed Guillain Barre syndrome 10 days after the first symptoms.
      Four patients died, all had pneumonia. CONCLUSION: Younger people were more
      likely to be infected with influenza A H1N1 2009. The clinical manifestations
      were similar to the seasonal influenza. However, the mortality rate was much
      higher, particularly in patients who developed pneumonia. In this study, all
      patients who died had existing underlying medical conditions.

PMID- 21863672
TI  - Cross-clade immunogenicity and antigen-sparing with an AS03(A)-adjuvanted
      prepandemic influenza vaccine in a Thai population.
AB  - OBJECTIVE: The present study (NCT00449670) in Asian subjects (18-60 years)
      evaluated the manufacturing consistency of four formulations of 3.75 mg AS03(A)
      adjuvanted H5N1 influenza vaccine, in terms of post-immunization Hemagglutination
      Inhibition (HI) titers against the A/Vietnam/1194/2004 and A/Indonesia/05/2005
      strains. The immunogenicity and safety of the vaccine in the Thai population are
      reported herein. MATERIAL AND METHOD: Subjects were randomized (2:2:2:2.:1:1)
      between four vaccine groups and two control groups to receive two doses of either
      the AS03(A)-adjuvanted or non-adjuvanted H5N1 vaccine formulations, 21 days
      apart. Sera were assayed for HI antibody titers against the two strains. RESULTS:
      After the second dose of AS03(A)-adjuvanted vaccine, 94.2% subjects in the H5N1
      AS03(A) groups seroconverted and 94.9% subjects were seroprotected against the
      A/Vietnam/1194/2004 strain. Cross-clade immune response against the
      A/Indonesia/05/2005 strain was observed. All vaccine formulations had an
      acceptable safety profile. CONCLUSION: This antigen-sparing AS03(A)-adjuvanted
      influenza vaccine could be a suitable candidate for combating and mitigating
      future influenza pandemics.

PMID- 21863673
TI  - Epidemiology of candidemia in Songklanagarind Hospital.
AB  - OBJECTIVE: To study the epidemiology of candidemia patients in Songklanagarind
      Hospital. MATERIAL AND METHOD: A retrospective study examining the
      epidemiological data of candidemia patients in Songklanagarind Hospital, a
      referral center in southern Thailand, between January 2004 and December 2009.
      RESULTS: Two hundred six candidemia inpatients had an overall 54% mortality rate.
      The median age of the patients was 53 years (range: 1-98 years). Length of
      hospital stay was an average of 55 days. Most of them (129, 62.6%) were admitted
      in a non-intensive care unit (non-ICU). The most common associated condition was
      solid organ malignancy (67, 32.5%). Most of the patients (181, 88%) had a history
      of broad spectrum antibiotic usage; however, in the non-broad spectrum
      antibiotics group solid organ malignancy was still the most common associated
      condition. Candida albicans and non-albicans Candida accounted for 83 (40.3%) and
      123 (59.7%) cases, respectively. Higher mortality rates were significantly
      related with intensive care unit (ICU) admission, elderly patients, and the
      presence of solid organ tumors, hematologic malignancies, and neutropenia, and
      influenced by intubation with a mechanical ventilator, central venous or urethral
      catheterization, surgical procedures, and administration of antibiotics.
      CONCLUSION: Candidemia can cause a high mortality rate that is influenced with
      many independent risk factors including surgical and medical interventions. Non
      albicans Candida is more common than Candida albicans whereas each mortality rate
      was not significantly different.

PMID- 21863674
TI  - Using digital ECG consultation system to facilitate cases for ST-elevation MI in
      Saraburi Hospital.
AB  - OBJECTIVE: To study the efficacy of fast track managed care and in-hospital
      outcomes after applying the Applied Digital 12 leads ECG Consultation System
      (ADECS) to the routine ST segment elevation myocardial infarction (STEMI) fast
      track guideline in Saraburi Hospital. MATERIAL AND METHOD: The data were
      collected from a prospective registry of all chest discomfort patients who were
      admitted by STEMI fast track care between January 1, 2008 and October 31, 2010.
      RESULTS: Two hundred forty eight STEMI patients were divided into two groups
      (before; n = 123 and after applying ADECS; n = 125). Mean age was 62.35 +/- 12.85
      years and 70.2% were male. Common atherosclerosis risk factors were dyslipidemia
      (80.2%), hypertension (71.8%) and smoking (40.7%). The agreement of STEMI
      diagnosis between emergency department (ED) and ward improved from moderate to
      good level (Kappa value = 0.602; p < 0.001 vs. 0.718; p < 0.001). Mean/median of
      door to needle time (DTNT) and percentage of STEMI patients receiving
      thrombolytic therapy who achieved DTNT within 30 minutes were significantly
      improved, showing 73.24 +/- 54.78/65 vs. 46.05 +/- 33.88/30 minutes; p < 0.001
      and 6% vs. 50.6%; p < 0.001 respectively. Mean/median of total ischemic time
      (TIT) was not different, 250.13 +/- 139.09/225 vs. 254.21 +/- 163.12/226 minutes;
      p = 0.873 due to long symptom onset to hospital arrival time (SHAT), 176.90 +/-
      130.08/145 vs. 208.16 +/- 167.38/165 minutes; p = 0.218, which corresponded to
      the same of all in-hospital outcomes. Only the TIT within 180 minutes could show
      decreasing mortality rate but statistically insignificant, 13.5% vs. 20.7%; p =
      0.369. Major bleeding complication was not different between thrombolytic
      infusion at ward or at ED, 4.1% vs. 4.8%; p = 1.00. CONCLUSION: ADECS should be
      included in routine fast track care and thrombolysis should be initiated infusion
      in Emergency Department for all STEMI patients. Short DTNT was not enough to
      improve in-hospital outcomes. The continuous improvement should be focused on the
      SHAT and routine practice with quality assessment process.

PMID- 21863676
TI  - Development of the Thai Knee Osteoarthritis Screening Questionnaire (Thai-KOA-SQ)
      in Kanleurng Sub-District, Nakronpanom Province.
AB  - OBJECTIVE: To develop a simple questionnaire to use for screening Thai people for
      knee osteoarthritis (OA). MATERIAL AND METHOD: Subjects' characteristics and data
      covering all known risk factors for OA were collected from a sample of villagers
      at Kanleurng Sub-District, Nakronpanom Province. Hip, knee, and finger
      radiographs were taken from all subjects (n = 146) to diagnose OA. Multiple
      logistic regression was used to select the items contained in the questionnaire.
      A ROC curve was used to define the best cut-off point and distinguish between OA
      and non-OA. RESULTS: Three factors were identified as being associated with knee
      OA and were included in a questionnaire. The Thai-KOA-SQ included questions about
      knee pain, age and body mass index (BMI). The questionnaire has 79.2%
      sensitivity, 78.4% specificity and 85.1% for the area under the ROC curve.
      CONCLUSION: This questionnaire should be validated in a large group of people, in
      order to be further developed as the screening questionnaire for knee OA in the
      general Thai population.

PMID- 21863675
TI  - Laparoscopic radical prostatectomy: oncological and functional outcomes of 559
      cases in Siriraj Hospital, Thailand.
AB  - OBJECTIVE: To evaluate the results of oncological and functional outcomes of
      laparoscopic radical prostatectomy (LRP) during the first five years experience
      in Siriraj hospital. MATERIALS AND METHOD: Between September 2004 and September
      2009, the functional and oncological outcomes of 559 patients that underwent LRP
      were retrospectively evaluated. RESULTS: The distribution of pathological T stage
      was T2 (52.1%), T3 (39.9%), and T4 (2.9%). Lymph node metastasis (N1) were found
      in 19 patients (3.4%). The positive margin rates in pT2a-b, pT2c, pT3a, pT3b and
      pT4 were 13.2%, 34.7%, 65.9%, 72.7% and 76.9%, respectively. The 3-year
      biological progression free survival (bPFS) rate for all patients was 87.2%.
      Three-year bPFS rates in pT2a-b, pT2c, pT3a, pT3b and pT4 were 96.3%, 93%, 75%,
      55.6% and 62.5% respectively. The continent rate at 12 months was 84% and potency
      rate at 12 months in group that received bilateral nerve sparing was 29.1%.
      CONCLUSION: The oncological and functional results of our first LRPs in Thai men
      are acceptable and compared well with the early experience of previous studies.
      However, longer follow up is needed for further evaluation.

PMID- 21863677
TI  - Visual analogue scale foot and ankle: validity and reliability of Thai version of
      the new outcome score in subjective form.
AB  - BACKGROUND: Nowadays, measuring score in the form of subjective questionnaires is
      the important tool for clinical evaluation of the foot and ankle-related
      problems. VisualAnalogue Scale-Foot and Ankle (VAS-FA) is the newly developed
      subjective questionnaire, which has sufficiency of validity and reliability from
      a previous study OBJECTIVE: Translate the original English version of VAS-FA into
      the Thai version and evaluate the validity and reliability of Thai VAS-FA in
      patients with foot and ankle-related problems. MATERIAL AND METHOD: According to
      the forward-backward translation protocol, original VAS-FA was translated into
      the Thai version. Thai VAS-FA and validated Thai Short Form-36 (SF-36)
      questionnaires were distributed to 42 Thai patients to complete. For validation,
      Thai VAS-FA scores were correlated with SF-36 scores. For reliability, the test
      retest reliability and internal consistency were analyzed. RESULTS: Thai VAS-FA
      score demonstrated the sufficient correlations with physical functioning (PF),
      role physical (RP), bodily pain (BP) domains, and total score of SF-36
      (statistically significant with p < 0.001 level and r > 0.5 values). The result
      of reliability revealed highly intra-class correlation coefficient as 0.995 from
      test-retest study. The internal consistency was excellent with Cronbach alpha:
      0.995. CONCLUSION: The original VAS-FA score is a well-validated, subjective,
      visual-analogue-scale based outcome score. The Thai version of VAS-FA form
      maintained the validity and reliability of the original version. This newly
      translated-validated score can be distributed for the evaluation of the
      functions, symptoms, and limitation of activities in Thai patients with foot and
      ankle problems.

PMID- 21863678
TI  - Application of mometasone spray to reduce sore throat after tracheal intubation.
AB  - BACKGROUND: Many factors in tracheal intubation lead to postoperative sore throat
      from mucosal injury. Mometasone furoate spray is a moderate potency
      corticosteroid that prevents influx of inflammatory cells into the mucosa. The
      present study assessed the efficacy of this drug for reducing postoperative sore
      throat. MATERIAL AND METHOD: A prospective, randomized, double blind, controlled
      study was completed Forty-two patients undergoing general surgery with general
      anesthesia were randomized into two groups, momethasone and NSS group sprayed at
      the endotracheal tube cuff vocal cords, epiglottis and pharynx at the time of
      tracheal intubation. All the patients were evaluated on the incidence and
      severity of the sore throat at first, sixth, and 24 hour after surgery. RESULTS:
      The sore throat after tracheal intubation was significantly less severe after
      momethasone spray was used than after NSS was used at first, sixth and 24 hours
      after surgery. The incidences of sore throat in the momethasone group were also
      significantly fewer than in the SS group at sixth and 24 hour post operation (20%
      vs. 50% and 10% vs. 40%, respectively) but at the first hour that the incidence
      was not significantly different (40% vs. 75%). Number needed to treat at the
      first hour was 2.86, sixth hour was 3.33 and 24 hour was 3.33. CONCLUSION:
      Application of mometasone spray reduces postoperative sore throat after tracheal
      intubation.

PMID- 21863679
TI  - Comparison of effective-site target controlled infusion and manually controlled
      infusion of propofol for sedation during spinal anesthesia.
AB  - OBJECTIVE: Compare the efficacy of sedation of propofol infusion during spinal
      anesthesia between effective-site target controlled infusion and manually
      controlled infusion during spinal anesthesia. MATERIAL AND METHOD: Sixty
      inpatients scheduled for elective surgery undergoing spinal anesthesia were
      studied. The patients were allocated to one of two groups. Each group has 30
      patients. The TCI group (n = 30) received propofol infusion using effective-site
      target controlled infusion. The initial target concentration of the effective
      site of propofol was 1.5 microg/ml. The MCI group (n = 30) received initial bolus
      0.5 mg/kg and initial infusion rate 1.5 mg/kg/hr. The anesthesiologist adjusted
      to increase or decrease the infusion rate in both groups every minute in order to
      maintain the desired level of sedation (OAA/S score of 3 or 4). Hemodynamic,
      OAA/S score, the induction time, propofol dose, complications were recorded.
      RESULTS: The TCI group achieved the desired level of sedation (OAA/S score 3 or
      4) faster than MCI group. The patients in TCI group had sedation score < 3 more
      than MCI group during surgery. Mean arterial pressure of TCI group were
      significantly lower than the MCI group at 15, 30, 45 min. Four patients in the
      TCI group was experienced airway obstruction. Two patients in the TCI group
      aspirated saliva and choked when they were sleeping. Eight patients in the TCI
      group and one patient in the MCI group were restless and there were intermittent
      patient movements. CONCLUSION: The clinical benefit when used for sedation during
      spinal anesthesia of MCI was not different from TCI. There were complications in
      the TCI group more than the MCI group.

PMID- 21863680
TI  - Kinking of catheters during translaryngeal jet ventilation: a bench model
      investigation of eight devices.
AB  - OBJECTIVE: To evaluate oxygen flow through several transtracheal devices in
      native and right angle kinked states. MATERIAL AND METHOD: Eight catheter-over
      needle, and two oxygen conveyance devices (Enk Flow Modulator 10 L/min flow and
      Manujet III Jet device 15, 30, 50 psi) were examined. Oxygen flow from each
      catheter was measured five times with three insufflation patterns [continuous
      insufflation, one second insufflation/one second pause (1:1), one second
      insufflation/three second pause (1:3)] in both native, and 90 degree kinked
      condition. RESULTS: During continuous insufflation, all but the 20G catheter
      delivered flows of more than 7 L/m with all conveyance pressures. With a 1:1
      insufflation/pause ratio, catheters smaller than 16G were able to deliver 7 L/min
      flow only with driving pressures of 30 and 50 psi. With a 1:3 insufflation ratio,
      no catheter could deliver adequate flow with 15 psi (manujet) or with the Enk
      Flow modulator Only the Cook catheter and 14G Ravussin were capable at 30 psi.
      Only the Cook Transtracheal Jet Ventilation Catheter could deliver adequate flow
      in kinked position, but only at 50 psi. CONCLUSION: Needle-catheters designed for
      vascular access are marginally capable of effective TJV. The Cook Transtracheal
      Jet Ventilation catheter proved to be the most robust device in the kinked state,
      but only when combined with a high-pressure oxygen conveyance system.

PMID- 21863681
TI  - Development of a refractive error quality of life scale for Thai adults (the REQ
      Thai).
AB  - OBJECTIVE: To develop a scale for measuring refractive error quality of life
      (QOL) for Thai adults. MATERIAL AND METHOD: The full survey comprised 424
      respondents from 5 medical centers in Bangkok and from 3 medical centers in
      Chiangmai, Songkla and KhonKaen provinces. Participants were emmetropes and
      persons with refractive correction with visual acuity of 20/30 or better An item
      reduction process was employed by combining 3 methods-expert opinion, impact
      method and item-total correlation methods. The classical reliability testing and
      the validity testing including convergent, discriminative and construct validity
      was performed. RESULTS: The developed questionnaire comprised 87 items in 6
      dimensions: 1) quality of vision, 2) visual function, 3) social function, 4)
      psychological function, 5) symptoms and 6) refractive correction problems. It is
      the 5-level Likert scale type. The Cronbach's Alpha coefficients of its
      dimensions ranged from 0.756 to 0. 979. All validity testing were shown to be
      valid. The construct validity was validated by the confirmatory factor analysis.
      A short version questionnaire comprised 48 items with good reliability and
      validity was also developed. CONCLUSION: This is the first validated instrument
      for measuring refractive error quality of life for Thai adults that was developed
      with strong research methodology and large sample size.

PMID- 21863682
TI  - An evaluation of a new in-house serum and urine ELISA test for detection of
      Helicobacter pylori infection in Thai population.
AB  - OBJECTIVE: Non-invasive tests play significant roles in the test-and-treat
      approach of Helicobacter pylori management. The detection of Helicobacter pylori
      antibodies in urine and serum is an easy and inexpensive way to diagnose this
      infection. In the present study, the authors developed an in-house serum and
      urine ELISA tests for H. pylori antibodies and evaluated their performance in a
      Thai population. MATERIAL AND METHOD: One hundred thirty eight dyspeptic patients
      were recruited. All subjects underwent upper endoscopy and one antral biopsy was
      obtained for rapid urease test, which was used as a standard reference. Urine and
      serum samples were collected before the procedure to run in-house ELISA test.
      RESULTS: Thirty (22%) subjects were positive for the rapid urease test and 108
      (78%) were negative. Urine and serum optical density were significantly lower in
      the urease negative group (p = 0.011 and p < 0.001 respectively), while there
      were no differences in age, gender, or endoscopic findings between the two
      groups. Sensitivity, specificity, negative predictive value, positive predictive
      value, and accuracy of urine and serum ELISA tests were 72% vs. 96.3%, 63.5% vs.
      627%, 89.6% vs. 98.5%, 33.3% vs. 40.6%, and 64.5% vs. 69.8% respectively.
      CONCLUSION: In-house serum ELISA test for H. pylori antibodies yielded a very
      good sensitivity with acceptable specificity, whereas urine ELISA was unable to
      produce satisfactory sensitivity or specificity

PMID- 21863683
TI  - Pattern and risk factors of alcohol withdrawal delirium.
AB  - OBJECTIVE: To determine the incidence, prescribing risk factors of alcohol
      withdrawal delirium (AWD), and factors complicating AWD, in alcohol dependent
      patients hospitalized for alcohol detoxification. MATERIAL AND METHOD: Patients
      attending the detoxification program at Chiang Mai University Hospital and the
      Northern drug dependence treatment center between May and September 2005 were
      assessed. Patients with signs of AWD at baseline were excluded. Incidence, risk
      factors, and dosage of benzodiazepines of patients with and without subsequent
      AWD were compared Risk factors that prolonged the course of AWD were analyzed.
      RESULTS: Nineteen male patients were assessed. Ten patients (52.6%) developed AWD
      despite receiving benzodiazepine detoxification. Risk factors of age, previous
      history of AWD and epilepsy, alcohol use history, frequency and quantity of
      drinking, signs of simple withdrawal at first admission, and dosage of
      benzodiazepines were not significantly different between the groups. However,
      patients with systolic blood pressure at first admission (> 120 mmHg) had longer
      duration of AWD than those without abnormal blood pressure (72.0 +/- 53.7 hr
      versus 168.0 +/- 24.0 hr, respectively, p = 0.038). CONCLUSION: The incidence of
      AWD was relatively high despite treatment. Although the present study did not
      find any risk factor predicting AWD. AWD patients hypertensive at the first
      admission had significantly longer duration of delirium. Physicians should be
      aware of monitor and treat hypertensive state and give early treatment of alcohol
      withdrawal with adequate doses of benzodiazepines to decrease morbidity and
      mortality of AWD.

PMID- 21863684
TI  - Abdominal epilepsy: an uncommon of non-convulsive status epilepticus.
AB  - OBJECTIVE: To recognize abdominal epilepsy in adults. MATERIAL AND METHOD: Case
      report. RESULTS: Case 1: A 21-year-old woman with DM type I presented with a 2
      month history involving four episodes of severe abdominal pain and vomiting, each
      of which lasted four to five days. She had a recurrence every two weeks. The EEG
      revealed 'spike and wave ' and she was started an intravenous phenytoin that
      resolved the symptoms. Case 2: A 20-year-old woman with DM type I was admitted
      with a 2-month history of recurring severe left upper quadrant pain associated
      with occasional nausea but no vomiting. She experienced two more episodes of
      generalized tonic-clonic seizures and was treated with 300 mg phenytoin given
      orally The abdominal pains gradually subsided and she was symptom-free within two
      days. An EEG showed frequent sharp waves. She was treated with 10 mg intravenous
      diazepam and her symptoms and sharp waves disappeared within two minutes. Case 3:
      A 46-year-old man with DM type I was admitted with a four-month history of
      recurring severe epigastric pain and vomiting. His physical examination,
      laboratory tests, and extensive investigation for a primary GI disorder revealed
      nothing unusual. The EEG revealed spike and wave and he was treated with
      intravenous AED (phenytoin) loading after which the symptoms disappeared.
      CONCLUSION: Physicians should consider abdominal epilepsy in diabetics with
      recurrent, intractable abdominal pain in whom extensive investigations for
      primary gastrointestinal (GI) disorders are unremarkable.

PMID- 21863685
TI  - Oculomotor nerve schwannoma: a case report and review of the literature.
AB  - BACKGROUND: Oculomotor nerve schwannomas are extremely rare tumors. There are
      only 40 cases reported in the literature. There is no standard treatment for
      these rare tumors. CASE REPORT: The authors have reported a case of a 41-year-old
      Thai man presenting with progressive visual loss of the left eye for 6 months
      without diplopia. Visual acuity was 20/70 in the right and 20/400 in the left.
      There was no limitation of eye movement. MRI showed a 42.5 ml mass in the
      suprasellar region compatible with a schwannoma. The patient underwent a
      leftpterional craniotomy with partial tumor removal. The pathological section
      confirmed a diagnosis of schwannoma and the patient received postoperative
      stereotactic radiotherapy CONCLUSION: Options for treating these rare tumors
      include clinical observation, surgical resection or stereotactic radiation. High
      incidence of complete third nerve palsy following surgery has been reported in
      the literature. Therefore, a subtotal removal of large oculomotor schwannoma
      followed by stereotactic radiotherapy could provide a safer alternative compared
      to radical surgery.

PMID- 21863686
TI  - Transpyloric prolapse of a pedunculated polypoid gastric carcinoma: a case report
      and review of the literature.
AB  - Gastroduodenal intussusception is not a common clinical condition. It is usually
      caused by transpyloric prolapse of a benign gastric lesion into the duodenum. In
      the present report, the authors present an extremely rare case of gastroduodenal
      intussusception in which gastric carcinoma served as the lending point. Pre
      operative diagnosis was made from endoscopy and biopsy. The patient was treated
      successfully by subtotal gastrectomy with D2 lymph node dissection. The clinical
      presentation, diagnosis, and management of this entity were discussed and the
      literature was reviewed. Both the condition itself and the leading tumor, gastric
      carcinoma, are extremely rare and to the authors' knowledge. This is the first
      report in Thailand.

PMID- 21863687
TI  - Current status of the research ethics committees in Thailand.
AB  - BACKGROUND: Many research ethics committees (RECs) have been established to
      review biomedical research involving human subjects in many research institutes.
      The purpose is "To protect rights and welfare of human research participants". It
      is necessary to determine how many research ethics committees have been
      established in Thailand and whether they have a high enough standard toprotect
      the rights and welfare of human research subjects. OBJECTIVE: To determine the
      status of research ethics committees in Thailand. MATERIAL AND METHOD: One
      hundred thirty survey questionnaires were distributed by mail to medical schools
      of universities, public hospitals under the Ministry of Public Health, private
      hospitals, and research institutes. RESULTS: Seventy-eight questionnaires were
      returned. Thirty respondents had standard Operating Procedures (SOP). Twenty-two
      RECs had their own office while 36 had to share the office with other departments
      or units. Board meeting frequency was once a month. The average number of
      committee members was 14 and the majority was scientific members. Absence of
      nonaffiliated members was found in RECs (20.6%). Thirty RECs had never provided
      training for REC members and investigators, the other 48 provided training at
      least once a year Decision are made by consensus in 51 and majority vote in 14
      RECs. Twenty-two respondents managed conflicts of interest (COI) by asking those
      members to leave the meeting before a decision was finalized. Thirty-nine RECs
      required continuous review after approval of the protocols. CONCLUSION: Strong
      support from the organization leader is a key factor to efficiency and high
      standards of REC operation. Developing a network of RECs will be useful for
      future development. REC members still need knowledge to better protect the
      rights, safety, and well-being of research participants.

PMID- 21863688
TI  - [Recent changes in the paradigm of limbic encephalitis].
AB  - In the recent years, novel antibodies associated with limbic encephalitis have
      been described, which target such extracellular receptors or proteins that have
      been already indicated in the pathogenesis of hereditary or degenerative
      diseases. In a number of cases, where pathogenic role of antibodies generated
      against the voltage-gated potassium channel (VGKC) had been presumed, antibodies
      against a trans-synaptic scaffolding protein, LGI1 were indicated. Antibody
      response against NMDA-receptors has been suggested as a major cause of limbic
      encephalitis especially in young females, resulting in a typical clinical
      syndrome sometimes triggered by an ovarian teratoma. Antibodies against other
      receptors essential in synaptic transmission and plasticity (AMPA and GABA,
      receptors) have been also indicated, partially elicited by paraneoplastic
      processes. Such antibodies against surface proteins result in severe but
      potentially treatable diseases due to reversible internalization of the antigens
      crosslinked by the bivalent antibodies. In contrast, the rare classical
      onconeural antibodies reacting with intracellular targets (anti-Hu, anti-Ta/Ma2,
      anti-CV2/CRMP5) may elicit additional symptoms beside limbic encephalitis and the
      prognosis of such syndromes is poor.

PMID- 21863689
TI  - Modeling of human movements, neuroprostheses.
AB  - Modeling of human movements became very important as modern methods in
      informatics and engeniering are available to discern human movement
      characteristics that were hidden before. The construction of models of neural
      control and mechanical execution of human movements helps the diagnosis of
      movement disorders and predicts the outcome of clinical intervention and medical
      rehabilitation. Here I present methods for recording kinematic and muscle
      activity patterns. Measurements can be compared with predicted movement patterns
      based on mathematical models. There are an infinity of different muscle activity
      patterns or joint rotation patterns to perform a given motor task. I present the
      main approaches that are used to find such solutions from the infinity of choices
      that might be employed by the central nervous system. I present a practical
      application of movement modeling: In rehabilitation of spinal cord injured
      patients we develop and apply artificially controlled neuroprostheses to generate
      active cycling lower limb movements in the patients of the National Institute for
      Medical Rehabilitation.

PMID- 21863690
TI  - [Extension of polynomial analysis of interstitial I-125 brachytherapy for 48
      months].
AB  - OBJECTIVE: Previously we described from 20 patients' data with our new
      "polynomial prediction approach" the volumetrical changes following gliomas 1-125
      brachytherapy. The aim of this study is to extend the polynomials for 48 months,
      and to carry out multivarial analysis of several different aspects. METHODS: 20
      inoperable low-grade gliomas were followed for a 48-month period after 1-125
      interstitial irradiation. The delivered dose on the tumor surface was 50-60 Gy.
      Dose planning and image fusion were done with the BrainLab Target 1.19 software,
      mathematical and statistical computations were carried out with the Matlab
      numeric computation and visualization software. Volumes of tumor necrosis,
      reactive zone and edema referred to as "triple ring" were measured on image fused
      control MRI and planning CT images. The measured volumes were normalized with
      respect to the reference volumes. Mean values of volumes were determined, then
      polynomials were fitted to the mean using the polynomial curve fitting method.
      The accuracy of our results was verified by correlating the predicted data with
      the measured ones. RESULTS: We have found that the edema reaches its maximum two
      times after irradiation during the 48 months follow up period. We have shown that
      small tumors react more rapidly and creating greater volumes of the "triple ring"
      than bigger ones. CONCLUSIONS: The polynomial prediction approach proposed here
      reveals the dynamics of triple ring for 48 months. The derived polynomials and
      the multivarial analysis carried out afterwards help to (i) design the best
      treatment, (ii) follow up the patient's condition and (iii) plan reirradiation if
      necessary.

PMID- 21863691
TI  - [Phylo- and ontogenetic aspects of erect posture and walking in developmental
      neurology].
AB  - The group or profile of elementary neuromotor patterns is different from the
      primitive reflex group which is now called the "primitive reflex profile." All
      these elementary neuromotor patterns are characterized by a high degree of
      organization, persistence, and stereotypy. In many regards, these patterns are
      predecessors or precursors of from them the specific human motor patterns which
      appear spontaneously later as crawling, creeping, sitting, and walking with erect
      posture. On the basis of our experiences it can be stated that the elementary
      neuromotor patterns can be activated in all neonates and young infants as
      congenital motor functions. With regards to their main properties and functional
      forms, the normal patterns can be divided into two main groups: (1) One group is
      characterized by lifting of the head and complex chains of movements which are
      directed to the verticalization of the body; (2) The other group is characterized
      by complex movements directed to locomotion and change of body position. The
      neuromotor patterns can be activated by placing the human infant in specific body
      positions that trigger the vestibulospinal and the reticulospinal systems, the
      archicerebellum and the basal gangliae. Most of these systems display early
      myelinisation and are functioning very soon. Many of the elementary neuromotor
      patterns reflect the most important - spontaneously developing forms of human
      movements such as sitting upright in space and head elevation crawling and
      walking. The majority of the human neuromotor patterns are human specific. When
      the infant is put in an activating position, crawling, sitting up, and walking
      begin and last as long as the activating position is maintained. Each elementary
      neuromotor pattern is a repeated, continuous train of complex movements in
      response to a special activating position. The brainstem is not sufficient to
      organize these complex movements, the integrity of the basal ganglia is also
      necessary. Elementary sensorimotor patterns during human ontogenesis reflect
      phylogenetic develpoment of species specific human functions. During ontogenesis
      spontaneous motor development gradually arises from these early specific
      sensorimotor predecessors.. The regular use of the elementary neuromotor patterns
      for diagnostic puposes has several distinct advantages. The neuromotor patterns
      have a natural stereotypy in normal infants and, therefore, deflections from this
      regular pattern may be detected easily, thus, the activation of the elementary
      neuromotor pattern is a more suitable method for identifying defects in the motor
      activity of the neonate or young infant than the assessment of the primitive
      reflexes. The "stiumulus positions," which activate specific movements according
      to how the human neonate or young infant is positioned, do not activate such
      motor patterns in neonate or young primates including apes. The characteristic
      locomotor pattern in these adult primates, including the apes, is swinging and
      involves brachiation with an extreme prehensility. This species specific motor
      activity is reflected in the orangutan and gibbon neonates by an early extensive
      grasp. However, according to our investigations, no crawling, creeping,
      elementary walk, or sitting up can be activated in them. Neonates grasp the hair
      of the mother, a vital function for the survival of the young. In contemporary
      nonhuman primates including apes, the neonate brain is more mature. Thus,
      pronounced differences can be observed between early motor ontogenesis in the
      human and all other primates. The earliest human movements are complex
      performances rather than simple reflexes. The distinction between primitive
      reflexes and elementary neuromotor patterns is essential. Primitive reflexes are
      controlled by the brainstem. All can be activated in primates. These reflexes
      have short durations and contrary to elementary sensorimotor patterns occur only
      once in response to one stimulus, e.g., one head drop elicits one abduction
      adduction of the upper extremities correlated to adduction and flexion of the
      lower extremities to a lesser degree with the Moro reflex. Elementary neuromotor
      patterns are much more complex and most of them including elementary walk may be
      elicited as early as the 19th-20th gestational week, though less perfectly than
      later.

PMID- 21863692
TI  - Combined evoked potentials in co-occuring attention deficit hyperactivity
      disorder and epilepsy.
AB  - BACKGROUND AND PURPOSE: Evoked potentials, both stimulus related and event
      related, show disturbances in attention deficit-hyperactivity disorder and
      epilepsies, too. This study was designed to evaluate if these potentials are
      characteristically influenced by the presence of the two diseases, individually,
      and in the case of co-occurrence. METHODS: Forty children were included, and four
      groups were formed, control group, ADHD group, epilepsy group and a group with
      the comorbidity of epilepsy and ADHD. Epilepsy patients were under proper
      antiepileptic treatment; ADHD patients were free of specific therapy. Brainstem
      auditory evoked potentials, visual evoked potentials and auditory P300 evaluation
      were performed. RESULTS: The latency of the P100 and N135 visual evoked potential
      components was significantly extended by the presence of epilepsy. If ADHD was
      concomitantly present, this effect was attenuated. Brainstem auditory evoked
      potential components were prolonged in the presence of the comorbidity,
      considering the waves elicited in the brainstem. P300 latencies were prolonged by
      the presence of co-occurring ADHD and epilepsy. Feedback parameters showed
      overall reduction of the tested cognitive performances in the ADHD group.
      CONCLUSION: Disturbances produced by the presence of ADHD-epilepsy comorbidity
      reveal hypothetically a linked physiopathological path for both diseases, and
      offers an approach with possible diagnostic importance, combined evoked potential
      recordings.

PMID- 21863693
TI  - [Initial clinical experience with radiofrequency-guided percutaneous vertebral
      augmentation in the treatment of vertebral compression fractures].
AB  - PURPOSE: Percutaenous Vertebroplasty (PVP) is effective in alleviating pain and
      facilitating early mobilization following vertebral compression fractures. The
      relatively high risk of extravertebral leakage due to uncontrolled delivery of
      low viscosity bone cement is an inherent limitation of the technique. The aim of
      this research is to investigate the ability of controlled cement delivery in
      decreasing the rate of such complications by applying radiofrequency heating to
      regulate cement viscosity. METHOD AND MATERIAL: Thirty two vetebrae were treated
      in 28 patients as part of an Ethics Committee approved multicenter clinical trial
      using RadioFreqency assisted Percutaenous Vertebral Augmentation (RF-PVA)
      technique. This technique is injecting low viscosity polymethylmethacrylate
      (PMMA) bone cement using a pressure controlled hydraulic pump and applying
      radiofrequency heating to increase cement viscosity prior to entering the
      vertebral body. All patients were screened for any cement leakage by X-ray and CT
      scan. The intensity of pain was recorded on a Visual Analog Scale (VAS) and the
      level of physical activity on the Oswestry Disability Index (ODI) prior to, one
      day, one month and three months following procedure. RESULTS: All procedures were
      technically successful. There were no clinical complication, intraspinal or
      intraforaminal cement leakage. In nine cases (29%) a small amount of PMMA entered
      the intervertebral space through the broken end plate. Intensity of pain by VAS
      was reduced from a mean of 7.0 to 2.5 and physical inactivity dropped on the ODI
      from 52% to 23% three months following treatment. CONCLUSION: In this small
      series controlled cement injection using RF-PVA was capable of preventing
      clinically hazardous extravertebral cement leakage while achieving outcomes
      similar to that of conventional vertebroplasty.

PMID- 21863694
TI  - [Pseudo abducens palsy].
AB  - In this study, we present two cases of different eye movement disorders with
      variable case histories but with the same end stage; abduction paresis of one of
      the eyes, which ceased when the other eye was covered. Our differential diagnosis
      is that either the ocular form of myasthenia gravis, convergence spasm or ocular
      myotonia could explain the symptoms. However, we hypothesize that the clinical
      picture corresponds to pseudo abducens palsy or focal dystonia of the extraocular
      muscle, which in turn could be the result of impaired inhibition of the tonic
      resting activity of the antagonistic medial rectus muscle. We offer an
      explanation for the patomechanism of pseudoabducens palsy and the variants of
      internuclear ophthalmoplegia.

PMID- 21863695
TI  - [Treatment of wide necked intracranial aneursyms in a two-step procedure with
      stent implantation and coils].
AB  - Since the introduction of electrolytically detachable coils the endovascular
      treatment of intracranial aneurysms is dynamically developing. The good results
      with this technique led to a progressive expansion of the indications. For the
      treatment of complex, wide-necked and fusiform aneurysms several new devices and
      techniques were developed. The introduction of a new device is possible after a
      feasibility study. In these studies the number of cases is low. Some risk factors
      or possible complications occur only after the introduction of a new device to
      the market.

PMID- 21863697
TI  - [Criticism of neurological services and suggestions for improvement based on the
      article by Daniel Bereczki and Andras Ajtay].

PMID- 21863696
TI  - Unilateral ptosis associated with paramedian thalamiic infarction.
AB  - The paramedian artery arises from P1 segment of posterior cerebral artery and
      supplies a variable extent of thalamus but usually the dorsomedian, median,
      internal medullary lamina and the intralaminar nuclei. The typical clinical
      picture of unilateral paramedian thalamic infarctions consist of arousal and
      memory disorders, language or visuospatial disorders depending on the side of the
      lesion accompanied with gaze palsies and sensory-motor deficits. Ipsilateral
      ptosis associated with paramedian thalamic infarctions has been rarely reported.
      We report a 31 years old patient presenting with unilateral ptosis and right
      sided facial numbness associated with right paramedian thalamic infarction.

PMID- 21863698
TI  - [Foreigners and lepers as strangers in early modern imperial towns].
AB  - This paper provides insight into interdependent processes by which leprosy and
      foreignness were constructed in early modern Germany. The results are based on a
      case study and further source-samples from Imperial towns of the Swabian and
      Franconian district. As it seems the early modern period was characterized by an
      ambivalent attitude towards lepers resulting in a variety of ways of inclusion
      and of exclusion for these persons: The separation from certain forms of social
      life in the towns (and in the villages belonging to the respective territory)
      followed the "suspicion" by other inhabitants caused by physical "signs" and the
      confirmed diagnoses of leprosy by medical experts. Such alienation from one
      community was juxtaposed by a right to enter the towns in rather specific
      circumstances as group of alms-beggars or part of a festive community and to join
      the community of leprosaria. The admission to such houses on the other hand was
      associated with the status of a burgher, a status, however, which could not be
      gained by everybody and was not fixed for life but was flexible. We found
      evidence that the status of leprosarium-"burgher" could be negotiated,
      interchanged, abandoned by lepers or be granted, refused, denied, suspended by
      the authorities--temporarily and permanently. By such means affiliation and
      foreignness were constructed. Preliminary analysis of numbers at ceremonies
      suggest that a large number of lepers was mobile--whether voluntarily or forced
      has still to be found out. And they represented the double fold estranged who,
      albeit, were temporarily included into the celebrating or commemorating
      community. Such forms of inclusion of the excluded, on the other hand, caused
      suspicion of simulation which became increasingly the preoccupation of the
      authorities.

PMID- 21863699
TI  - ["A decision meaning a new foundation...": from the Kaiser Wilhelm Institute for
      Anthropology, Human Genetics and Eugenics to the Max Planck Institute for
      Molecular Genetics].
AB  - The Max Planck Institute for Molecular Genetics (MPIMG) in Berlin-Dahlem dates
      its establishment to 1964. Its homepage makes no mention of its predecessor
      institutes, the Kaiser Wilhelm Institute for Anthropology, Human Genetics and
      Eugenics (KWIA) and the subsequent MPI for Comparative Genetics and Hereditary
      Pathology (MPIVEE). This article traces the two critical phases of transition
      regarding the constellations of academic staff, institutional and epistemic
      ruptures and continuities specific to the era. Only one of the five department
      heads from the final war years, Hans Nachtsheim, remained a researcher within the
      Max Planck Society (MPG); he nevertheless continued to advocate the pre-war and
      wartime eugenic agenda in the life sciences and social policy. The generational
      change of 1959/60 became a massive struggle within the institute, in which
      microbial genetics (with Fritz Kaudewitz) was pitted against human genetics (with
      Friedrich Vogel) and managed to establish itself after a fresh change in
      personnel in 1964/65. For the Dahlem institute, this involved a far-reaching
      reorientation of its research, but for the genetically oriented life sciences in
      the Max Planck Society as a whole it only meant that molecular biology, which was
      already being pursued in the West German institutes, gained an additional
      facility. With this realignment of research traditions, the Society was able to
      draw a line under the Nazi past without having to address it head-on.

PMID- 21863701
TI  - They said I was sick; turns out it was just a code.

PMID- 21863700
TI  - [Genetic testing in occupational medicine--conflicts and arguments within a
      historical perspective].
AB  - The article examines the positions and discussions on genetic testing in
      occupational medicine within a historical perspective. In the process, it shows a
      continuity of views regarding occupational medicine and its diagnostic
      approaches. While labor representatives mainly opposed the possibilities of
      genetic testing and particularly emphasized its selective nature, physicians
      stressed the preventive possibilities but nevertheless realized the importance of
      federal regulation. Interestingly enough, the discussions dealt exclusively with
      the modern possibilities of genetic testing, which played minuscule role in
      practice. On the other hand, family history, to this day, has attracted very
      little interest.

PMID- 21863702
TI  - The switch from ICD-9 to ICD-10. How to reduce claims and coding errors.

PMID- 21863703
TI  - ICD -10: A master data challenge.

PMID- 21863704
TI  - How agile is your claims adjudication system?

PMID- 21863705
TI  - The drive to coding compliance.

PMID- 21863706
TI  - EHR certification: getting comfortable with the concept.

PMID- 21863707
TI  - Meeting REMS head on.

PMID- 21863708
TI  - [Jet lag after birth].

PMID- 21863709
TI  - [Professional autonomy in pediatric nursing].

PMID- 21863710
TI  - [Pain assessment by nurses in extremely premature newborn infants in German
      speaking countries - a review of the literature].

PMID- 21863711
TI  - [Hematologic illnesses in children and adolescents].

PMID- 21863712
TI  - [A new after care clinic for children and adolescents with cancer and heart
      diseases].

PMID- 21863713
TI  - [Foot- and hand prints in newborn infants].

PMID- 21863714
TI  - [Transurethral urinary catheter: daily assessment of indications prevents urinary
      tract infections].

PMID- 21863715
TI  - [Preventing child abuse. The roots of love--a highly hormonal affair].

PMID- 21863716
TI  - How are your inter-species language skills?

PMID- 21863717
TI  - A hybrid approach.
AB  - Industry experts and HIE leaders have moved past early "model"-based debates to
      focus on creating core and value-added services, standardizing the meaning of the
      clinical data, and simplifying point to point connections necessary for
      information to flow between the HIE and providers EHRs.

PMID- 21863718
TI  - Channel surfing.
AB  - The federal Direct Project may be a viable interim solution that can enhance
      clinician-to-clinician communications as HIEs continue to be developed.

PMID- 21863719
TI  - Security in the cloud.
AB  - As more provider organizations look to the cloud computing model, they face a
      host of security-related questions. What are the appropriate applications for the
      cloud, what is the best cloud model, and what do they need to know to choose the
      best vendor? Hospital CIOs and security experts weigh in.

PMID- 21863720
TI  - Are you ready for an OCR audit?
AB  - Proposed rules aimed at strengthening HIPAA privacy and security requirements
      have put CIOs and security officers at provider organizations on alert. Experts
      weigh in on how the changes will play out and what it means for provider
      organizations.

PMID- 21863721
TI  - EHR solution for pediatric dose range checking.

PMID- 21863722
TI  - AMGA expresses concerns over ACOs.

PMID- 21863723
TI  - Electronic claims processing.

PMID- 21863724
TI  - Protecting patient identity.

PMID- 21863725
TI  - Data: the 'unsung' asset.

PMID- 21863726
TI  - The pieces of the hiring puzzle.

PMID- 21863727
TI  - [Modus operandi of insane offenders in multiple homicides].
AB  - Homicides committed by insane offenders have been rarely investigated from the
      forensic point of view in a comprehensive and detailed manner. The objective of
      the study was to describe and characterize the modus operandi and personal
      characteristics in cases when more than one victim was killed and the perpetrator
      was deemed insane in judicial proceedings. Differences between single and
      multiple-vitim homicides in the population of insane murderers were also
      examined. Complete dossiers and forensic examination reports of 21 homicide
      victims killed by 9 individuals were retrospectively analyzed. The comparative
      control group consisted of 41 cases with only one victim killed by a single
      insane perpetrator. The offence and offender variables were subjected to a
      comparative statistical analysis. The results indicated some specific factors
      that can be regarded as distinctive features more commonly observed in multiple
      vs. single victim killings perpetrated by insane individuals. There was a
      significant correlation between, psychosis with depressive delusions,
      emotional/affective motivation, common domicile and a positive relationship
      between the perpetrator and the victim, infanticide committed in the
      perpetrator's offspring, actions with elements of planning, attacking victims
      while asleep, attacking from the back rather than from the front, concentration
      and clustering of injuries in one region of the body and multiple psychotic
      homicides. The results and conclusions of this study can provide practical,
      useful implications for homicide investigations, offender profiling or forensic
      psychiatric and psychological evidence.

PMID- 21863728
TI  - [Development of a method for estimation of citalopram and desmethylcitalopram in
      nails and hair and its usefulness in forensic toxicology].
AB  - The report presents the possibility of using an alternative material of
      determining citalopram and its metabolite (desmethylcitalopram) in hair and
      nails. Citalopram (Cipramil, Citaratio, Citaxin, Oropram, Cital, Cilon, Aurex) is
      an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI)
      class, employed in treatment of depression, prevention of depressive disorders
      recurrence and in some anxiety disorders. The investigations were performed using
      liquid chromatography coupled with electrospray-ionization mass spectrophotometry
      (LC-ESI-MS). In the course of the study, the authors developed a method for
      isolation and identification of Citaprolam and its metabolite
      (desmethylcitaprolam) from hair and nails. Determination were performed in hair
      and nail samples collected from individuals who had been administered citalopram
      in therapeutic doses at least for 12 months before sample collection. Hair and
      nail samples were obtained 4, 6, 9 and 15 months after discontinuing drug
      administration. The concentration of citalopram in nails was 0.40-10.49 ng/mg and
      the concentration of desmethylcitalopram was 0.32-3.70 ng/mg. In hair, citalopram
      concentration was 1.04-8.69 ng/mg and for desmethylcitalopram, the concentration
      range was 0.07-1.27 ng/mg.

PMID- 21863729
TI  - [Evaluating the applicability of medical examinations constituting "the protocol
      of obtaining a blood sample" in measuring the degree of intoxication].
AB  - Breathalysing and blood analysis is the basic instrument of measuring the level
      of intoxication. Prior to collecting a blood sample, an individual suspected of
      being under the influence of alcohol is examined by a physician, who fills out
      the "protocol of obtaining a blood sample". This work aims at evaluating the
      applicability of the described examination in measuring the level of
      intoxication. In order to do so, our team analyzed 352 "protocols of obtaining
      blood sample" referred to the Forensic Laboratory KWP in Bydgoszcz, Poland, and
      compared them with the results of blood analysis. The results of the above
      analysis point to the fact that the elements of medical examination constituting
      "the protocol of obtaining a blood sample" are of a minor usefulness in
      determining the degree of intoxication with ethyl alcohol. The smell from the
      mouth and the conclusions formulated the examining physician prove to be the most
      useful. The summary usage of deviations from the norm does not seem to increase
      the usefulness of methods used within "the protocol of obtaining a blood sample"
      in evaluating the degree of intoxication.

PMID- 21863730
TI  - [Identification of rare genetic variants at DXS10074, DXS10079, DXS10146 and
      DXS10148 loci of investigator argus X-12 multiplex in the south Polish
      population].
AB  - In recent years, the analysis of X-linked short tandem repeats (X-STR), beside
      autosomal and Y-chromosomal STR loci, has become widely used in forensic genetic
      investigations. The usefulness of X-STRs markers in forensic medicine is
      confirmed by their high biostatistical parameters obtained for different
      populations. Such population studies performed on particular ethnic groups allow
      for demonstrating the presence of, rare genetic variants that are not included in
      the allelic ladders of commercially available multiplex kits. The presence of
      these alleles can increase the power of evidence. On the other hand, the off
      ladder alleles can be sometimes difficult to interpret. In this paper, X-STRs
      analysis was performed in a population sample of 200 unrelated females and males
      from the Southern Poland using Investigator Argus X-12 Kit. Seven rare off-ladder
      alleles were encountered: DXS10074*15.2, DXS10079*24, DXS10146*38.2,
      DXS10146*47.2, DXS10148*17, DXS10148*21.1 and DXS10148*22 that were not
      previously reported in the Polish population. Additionally, genetic transmission
      of these genetic variants was ascertained.

PMID- 21863731
TI  - [Population data analysis of miniSTR loci: D10S1248, D14S1434 and D22S1045 in the
      Pomerania-Kujawy region of Poland].
AB  - This paper presents the allele frequencies and forensic parameters of the three
      miniSTR loci D10S1248, D14S1434 and D22S1045 in the Pomerania-Kujawy region of
      Poland. Genomic DNA was extracted by a standard phenol-chloroform extraction
      procedure. The three miniSTR loci D10S1248, D14S1434 and D22S1045 were amplified
      in a triplex polymerase chain reaction with the primer sets designed by Coble and
      Butler in a GeneAmp PCR System 9700 (Applied Biosystems). The amplified products
      were separated and detected by capillary electrophoresis on an ABI PRISM 3100
      Genetic Analyzer (Applied Biosystems).The genotype frequency distributions showed
      no deviations from Hardy-Weinberg equilibrium expectations. The values of
      forensic parameters confirm that D10S1248 and D22S1045 are highly informative
      genetic markers, whereas D14S1434 is a moderately useful for forensic genetic
      identification purposes.

PMID- 21863732
TI  - [Evaluation of visualization of biological stains with the use of alternative
      light source (ALS) for the purpose of genetic identification. Part I. Blood and
      saliva stains analysis].
AB  - The objective of the investigation was evaluation of visualization of human blood
      and saliva stains with the use of alternative light source for the purpose of
      genetic identification. Experimental bloodstains on the bright base were the most
      clearly seen in the natural light and white light, up to blood dilution of 1:600.
      Complete typeability of AmpFISTR SGM Plus kit profiles was obtained from
      bloodstains at dilution 1:1500. Partial AmpFISTR SGM Plus kit profiles were typed
      from bloodstains at dilutions 1:1750 and 1:2000. Experimental saliva stains on
      the light-colored base were completely invisible in the natural light and white
      light, while they were visualized at wavelength range 300-415 nm through yellow
      goggles, and at wavelength range 300-455 nm through orange goggles at saliva
      dilution 1: 600. Complete typeability of AmpFISTR SGM Plus kit loci was obtained
      from saliva stains at dilution 1:1750. Partial AmpFISTR SGM Plus kit profiles
      were typed from saliva stains at dilution 1:2000. The wavelength of 455 nm and
      orange goggles were the optimal set for visualization of bloodstains on various,
      noncontrasting materials. Other useful wavelength/combinations of goggles were
      CSS light/red goggles. In case of saliva, the most useful general condition for
      visualization of stains on various, non-contrasting materials was with the
      wavelength set to 300-415 nm, while wearing yellow goggles. Other useful
      combinations of wavelength/goggles were 300-455 nm/orange or red goggles, and
      also CSS light/orange or red goggles.

PMID- 21863733
TI  - [Evaluation of visualization of biological stains with the use of alternative
      light source (ALS) for the purpose of genetic identification. Part II. Semen
      samples analysis].
AB  - Detection of seminal stains on items such as clothing and bedding is a
      significant element of investigation in sexual assault cases. The use of
      alternative light source may assist in their identification. The objective of the
      investigation was the evaluation of human semen visualization with the use of
      alternative light source for the purpose of genetic identification. The tests
      demonstrated that experimentally prepared semen stains on the bright base could
      be best seen in the natural light and white light when the semen was diluted at a
      ratio 1:10. The complete typeability of AmpFISTR SGM Plus kit loci was evaluated
      in semen which was diluted at a ratio 1:1750 and typeability of AmpFISTR SGM Plus
      kit loci was incomplete in semen diluted at a ratio 1:2000. After washing with
      laundry detergents, semen stains were still recognizable under ALS wavelength 455
      nm, while wearing orange goggles.

PMID- 21863734
TI  - [Saturation of the Polish mitochondrial DNA database].
AB  - The main objective of the study was a statistical evaluation of Polish
      mitochondrial DNA database, consisting of 1253 maternally unrelated individuals
      from seven different regions of Poland. Four relevant parameters were examined:
      haplotype diversity, nucleotide diversity, number of polymorphic positions and
      number of haplotypes, including HVS I and HVS II mtDNA regions. The results show
      that while haplotype and nucleotide diversities have already reached saturation
      level, the number of haplotypes and polymorphic positions rises continuously
      inside the database. These results indicate a need for a substantial increase in
      the number of haplotypes in Polish mitochondrial DNA database.

PMID- 21863735
TI  - [Cases of myocarditis and their effect on the mechanism of death].
AB  - In this study, we describe two cases with autopsy findings of interstitial
      myocarditis. They show that supplementing the autopsy with histopathological
      examination, even when the cause of death is thought to be clear and obvious, is
      extremely important as it can contribute valuable information to the case,
      including the circumstances of death. In the first case, we discussed a tram
      accident in which its driver was killed. The family of the deceased reported that
      he had been suffering from consciousness disturbances for some time, and
      additional radiological examinations demonstrated abnormalities in his neck blood
      vessels. In the second case, a pregnant woman was admitted to hospital after a
      cardiac and respiratory arrest. A cesarean section was carried out but the fetus
      was already dead. The woman was declared dead shortly after the operation.

PMID- 21863736
TI  - [Deaths during asphyxia induced to escalate sexual experience. Case reports].
AB  - The authors present two cases of deaths resulting from asphyxia of one of the
      partners in the act of intercourse to escalate their experience. The first case
      involved a heterosexual intercourse, in which a 30-year-old woman was led to
      state of hypoxia through choking and closing respiratory orifices. The other case
      represented a homosexual intercourse between two men, in which the victim's hands
      and legs were tied. Moreover, the partner put an open knot around the victim's
      neck and was holding it controlling the state of asphyxia, while performing an
      anal intercourse. Both presented victims practiced such paraphilia-associated
      behaviors in the past. The fact of sexual intercourse was confirmed in both cases
      by genetic analysis of the man's anus and the woman's oral cavity and vagina.
      This resulted in finding the genetic material of their partners. Escalating of
      sexual experience through inducing asphyxia of the nervous system is extremely
      dangerous and may result in death of one of the sexual partners, what has been
      proven by the present investigation.

PMID- 21863737
TI  - [Contribution of Polish forensic medicine specialists to the studies of war
      crimes committed in Katyn].

PMID- 21863739
TI  - [Mercury (and...) through the centuries].
AB  - Mercury has a long history, fascinating in its many aspects. Through the
      centuries--from ancient times to the present day--the metal in its various forms,
      also known under the name "quicksilver", accompanied the man and was used for
      diversified purposes. Today, mercury is employed in manufacturing thermometers,
      barometers, vacuum pumps and explosives. It is also used in silver and gold
      mining processes. Mercury compounds play a significant role in dentistry,
      pharmaceutical industry and crop protection. The contemporary use of mercury
      markedly decreases, but historically speaking, the archives abound in materials
      that document facts and events occurring over generations and the immense
      intellectual effort aiming at discovering the true properties and mechanisms of
      mercury activity. Mercury toxicity, manifested in destruction of biological
      membranes and binding of the element with proteins, what disturbs biochemical
      processes occurring in the body, was discovered only after many centuries of the
      metal exerting its effect on the lives of individuals and communities. For
      centuries, mercury was present in the work of alchemists, who searched for the
      universal essence or quintessence and the so-called philosopher's stone. In the
      early modern era, between the 16th and 19th centuries, mercury was used to
      manufacture mirrors. Mercury compounds were employed as a medication against
      syphilis, which plagued mankind for more than four hundred years--from the Middle
      Ages till mid 20th century, when the discovery of penicillin became the turning
      point. This extremely toxic therapy resulted in much suffering, individual
      tragedies, chronic poisonings leading to fatalities and dramatic sudden deaths.
      In the last fifty years, there even occurred attempts of mentally imbalanced
      individuals at injecting themselves with metallic mercury, also as a performance
      enhancing drug. Instances of mass mercury poisoning occurred many times in the
      past in consequence of eating food products poisoned with organic mercury
      compounds originating from the natural environment.

PMID- 21863738
TI  - [Documentation of course and results of crime scene reconstruction and virtual
      crime scene reconstruction possibility by means of 3D laser scanning technology].
AB  - The objective of the study was to present both the possibilities of documenting
      the course and results of crime scene reconstruction using 3D laser scanning
      technology and the legal basis for application of this technology in evidence
      collection. The authors present the advantages of the aforementioned method, such
      as precision, objectivity, resistance of the measurement parameters to
      manipulation (comparing to other methods), high imaging resolution, touchless
      data recording, nondestructive testing, etc. Moreover, trough the analysis of the
      current legal regulations concerning image recording in criminal proceedings, the
      authors show 3D laser scanning technology to have a full complete ability to be
      applied in practice in documentation of the course and results of crime scene
      reconstruction.

PMID- 21863740
TI  - [Accreditation of forensic laboratories].
AB  - According to the framework decision of the European Union Council, genetic
      laboratories which perform tests for the benefit of the law enforcement agencies
      and the administration of justice are required to obtain a certificate of
      accreditation testifying to compliance with the PN EN ISO/IEC 17025:2005
      standard. The certificate is the official confirmation of the competence to
      perform research, an acknowledgement of credibility, impartiality and
      professional independence. It is also the proof of establishment, implementation
      and maintenance of an appropriate management system. The article presents the
      legal basis for accreditation, the procedure of obtaining the certificate of
      accreditation and selected elements of the management system.

PMID- 21863741
TI  - [Mitochondrial disfunction in Parkinson's disease].
AB  - Mitochondrial structural and functional abnormalities in Parkinson's disease and
      experimental animal models of this pathology are described. Special attention is
      paid to the inactivation of mitochondrial enzymes, mutations in mitochondrial and
      nuclear DNA, and genomic and proteomic research of mitochondrial proteins in
      Parkinson's disease and experimental parkinsonism of animals.

PMID- 21863742
TI  - [ACE inhibitors--activators of kinin receptors].
AB  - Angiotensin converting enzyme (ACE) inhibitors are widely used for treatment of
      cardiovascular diseases. The effects of ACE inhibitors on the human bradykinin
      receptors were investigated. The mode of action of ACE inhibitors is considered.
      There is evidence that ACE inhibitors exert effects on the vascular system that
      cannot be attributed simply to the inhibition of ACE activity and accumulation of
      locally produced bradykinin. ACE inhibitors augment bradykinin effects on
      receptors indirectly by inducing cross-talk between ACE and the B2 receptor when
      enzyme and receptor molecules are sterically close, possibly forming a
      heterodimer. ACE inhibitors activate B1 receptors directly and independently of
      ACE via the zink-binding consensus sequence HEXXH, which is present in B1, but
      not in B2 receptor. Particular structure of B2 and B1 are represented, as well as
      receptor amino acids coupled with the G-proteins. Activation of kinin receptors
      by ACE inhibitors leads to clinically beneficial effects of ACE inhibitors.

PMID- 21863743
TI  - [Inhibition of no-dependent soluble human platelet guanylate cyclase by isatin].
AB  - Isatin (indole-dione-2,3) is an endogenous indole that exhibits a wide spectrum
      of biological and pharmacological activities. Physiologically relevant
      concentrations of isatin (ranged from 1 nM to 10 M) did not influence basal
      activity of soluble human platelet guanylate cyclase (sGC), but caused a bell
      shaped inhibition of the NO-activated enzyme. Inhibition of the NO-dependent
      activation by isatin did not depend on a chemical nature of the NO donors. The
      inhibitory effects of ODC (a heme-dependent inhibitor of sGC) and isatin were non
      additive suggesting that the inhibitory effect of isatin may involve the heme
      binding domain (possibly heme iron) and experiments with hemin revealed some
      isatin-dependent changes in its spectrum. Isatin also inhibited sGC activation by
      the allosteric activator YC-1. It is suggested that the bell shaped inhibition of
      the NO-dependent activation of sGC by isatin may be attributed to complex
      interaction of isatin with the heme binding domain and the allosteric YC-1
      binding site of sGC.

PMID- 21863744
TI  - [The analysis of interaction between lipoproteins and steroid hormones].
AB  - Using the methods of ultracentrifugation, gel-filtration and fluorescence
      quenching, we demonstrated, that plasma lipoproteins bind steroid hormones and
      can therefore play a role of their active transport form in an organism. High
      density lipoproteins have revealed the highest affinity to steroids for. It has
      been found, that protein component of lipoproteins takes part in the formation of
      lipoprotein-steroid complex. The apolipoprotein A-I, the main protein component
      of high density lipoproteins, is responsible for binding of steroid hormones. The
      calculated constants formation of the complexes of lipoproteins with steroid
      hormones testifies to specificity of linkage. The results obtained allow to
      considering real opportunity of transfer of steroid hormones into cell by a
      receptor-mediated endocytosis in structure of lipoproteins complexes.

PMID- 21863745
TI  - [The comparative study of the medical action of lyuteolin, rosmarinic acid and
      echinochrom A at experimental stress-induced cardiopathology].
AB  - The method of the physical load in condition of the coronary circulation of the
      blood disturbance, caused mesaton injection, induced development rat
      cardiopathology, bring about of the heart function decompensation and 40% death
      of experimenthal animals. Under electronic-microscopic study of rat
      cardiomyocytes are discovered signs to disorganizations of mitochondrial
      apparatus of these cells. Administration to therapeutic mode of luteolin and
      echinochrome A preparations has provided to 100% animal probability of survival.
      At the same time, mitochondrial apparatus of cardiomyocytes was characterized by
      the normal parameter i.e. given preparations have provided of defensive adative
      effect at cardiomyocytes level. Similar activities for rosmarinic acid have not
      shown. Study some metabolic parameter and endocrine status animal has also
      allowed revealing of therapeutic effect of luteolin and echinochrome A. Findings
      be evidence of that echinochrome A and luteolin capable to play the important
      positive role in metabolism of cardiomyocytes by stimulating of mitochondrial
      biogenesis and by changing of adaptative mechanisms of the organism
      cardiovascular system protection.

PMID- 21863746
TI  - [Evaluation of cytotocicity and efficiency of antioxidant protection of
      hydrophilic derivatives of 2,4,6-trialkylphenols in Escherichia coli cells].
AB  - The effects of five new derivatives of 2,6-dialkyl-4-propylphenole containing in
      para-radical different ionogenic groups (-SO3Na, -S-SO3Na, -S-(NH2)2Cl) in the
      presence and in the absence of hydrogen peroxide on the survival of E. coli
      AB1157 cells and its isogenic strain defective in repair enzyme genes were
      studied. Cell survival treated with hydrogen peroxide was remarkably increased in
      the presence of (3-(3,5-dimethyl-4-hydroxyphenyl)propyl)-1-sulphonate of sodium
      (Cl). Replacement of methyl ortho-radicals in the structure of Cl for tret-buthyl
      or cyclohexyl groups led to a decrease of the compounds ability to protect the
      cells from exogenic hydrogen peroxide. Between derivatives of 2,6-di-tret
      buthylphenol the compound with thiosulphonate group demonstrated properties
      comparable with those for its sulphonate analog, then a chloride of isotiurone at
      concentration 3 mM completely suppressed the growth of cells in presence and in
      the absence of H2O2. Compound Cl may be considered as most perspective for detail
      analysis as antioxidant.

PMID- 21863747
TI  - [Antioxidant enzymes in erythrocytes from hypertension patients receiving
      lisinopril monotherapy or combined lisinopril plus simvastatin therapy].
AB  - Statins and angiotensin-converting enzyme (ACE) inhibitors have beneficial impact
      on the serum cholesterol and blood pressure. It is supposed that statins and ACE
      inhibitors may modify the antioxidative status of erythrocytes. The study
      objective was to compare the effects of two treatments, lisinopril alone vs
      lisinopril plus simvastatin, on erythrocyte antioxidant enzyme activities. The
      study involved 32 patients with arterial hypertension, the initial serum total
      cholesterol, LDL-cholesterol and triglycerides within the normal range. Patients
      of two groups, each of 16 subjects, were treated with lisinopril (10 mg/day) or
      with lisinopril (10 mg/day) plus simvastatin (20 mg/day). Before and after 3 and
      6 months of follow-up therapy, activities of superoxide dismutase (SOD),
      catalase, glutathione peroxidase (GPx), glutathione reductase (GLR) in purified
      erythrocytes were determined. In all patients, significantly higher catalase
      activity (by 79.3-106.5%, p < 0.0001) and significantly lower GPx activity (by
      20.7-30.6%, p < 0.001) were observed after therapy as compared to the baselines.
      Just the same results were obtained in both groups (lisinopril and lisinopril +
      simvastatin), after both periods (3 and 6 month) of treatments. SOD activity was
      increased only in the lisinopril group and only after 6 months (p = 0.0345). No
      changes of GLR reductase activity were seen under all conditions indicated. Thus,
      the lisinopril monotherapy and combined lisinopril plus simvastatin therapy
      exhibit specific, pronounced and equipotent effects on antioxidant enzymes in
      human erythrocytes. Administration of lisinopril or lisinopril plus simvastatin
      may protect erythrocytes and other tissues from oxidative damage.

PMID- 21863749
TI  - [Lymphoid malignancies: progress in diagnosis and treatment].

PMID- 21863750
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: I.
      Pathogenesis and pathophysiology--recent findings; 1. Leukemia stem cells in
      acute lymphoblastic leukemia].

PMID- 21863748
TI  - [The influence of vitamin B group on monooxygenase activity of cytochrome P450
      3A4: pharmacokinetics and electro analysis of catalytic properties].
AB  - It was shown that vitamin B group permit to shorten the longitude of diclofenak
      therapy and to reduce the daytime dose of this drug. All three schemes of
      diclofenac treatment - only diclofenac, diclofenac plus 2 tablets of Gitagamp
      (mixture of vitamin B group), and diclofenac plus 4 tablets of Gitagamp--gave
      maximum value of diclofenal in blood through 1 hour after treatment. In the case
      of diclofenak treatment without vitamins Cmax corresponds to 1137.2 +/- 82.4
      ng/ml, with 2 tablets of Gitagamp--Cmax 1326.7 +/- 122.5 ng/ml, and with 4
      tablets--Cmax 2200.4 +/- 111.3 ng/ml. Positive influence of vitamin B group on
      the decrease of pain syndrome was shown. Pharmacodynamics and pharmacokinetics
      data were confirmed in electrochemical experiments with cytochrome P450 3A4. For
      enzyme immobilization screen printed graphite electrodes modified with gold
      nanoparticles and synthetic membrane-like compound didodecyldimethylammonium
      bromide (DDAB/Au) were used. Electrochemical analysis reviled the influence of
      vitamin B group on metabolism of non steroid anti inflammation drug diclofenac
      catalyzed by cytochrome P450 3A4. Riboflavin was the most effective inhibitor of
      diclofenac hydroxylation by cytochrome P450 3A4 as was compared at 300 M
      concentration of vitamin B group (B1, B2, B6). These data confirmed the
      opportunity of pharmacokinetic parameters regulation and the level of
      pharmacodynamic effects by the influence of vitamin B group on the catalytic
      activity of cytochrome P450 3A4.

PMID- 21863751
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: I.
      Pathogenesis and pathophysiology--recent findings; 2. Malignant lymphoma and
      related diseases].

PMID- 21863752
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: I.
      Pathogenesis and pathophysiology--recent findings; 3. Etiology and pathogenesis
      of plasma cell dyscrasia including multiple myeloma].

PMID- 21863753
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: I.
      Pathogenesis and pathophysiology--recent findings; 4. lymphoid malignancies and
      vires].

PMID- 21863754
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: II. Basic
      knowledge of lymphoid malignancies; 1. Classification of lymphoid malignancy].

PMID- 21863755
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: II. Basic
      knowledge of lymphoid malignancies; 2. Imaging studies in lymphoma].

PMID- 21863756
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: II. Basic
      knowledge of lymphoid malignancies; 3. Cytogenetic and molecular abnormalities].

PMID- 21863757
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: II. Basic
      knowledge of lymphoid malignancies; 4. Cell surface markers].

PMID- 21863758
TI  - [Lymphoid malignancies: Progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment; 1. Management of acute lymphoblastic leukemia and
      chronic lymphocytic leukemia].

PMID- 21863759
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment; 2. Malignant lymphoma; 1) Hodgkin lymphoma: diagnosis
      and treatment strategies].

PMID- 21863760
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment; 2. Malignant lymphoma; 2) Mature B cell lymphoma].

PMID- 21863761
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment; 2. Malignant lymphoma; 3) Mature T/NK-cell lymphomas].

PMID- 21863762
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment; 3. Diagnosis, laboratory examination, and treatment for
      multiple myeloma].

PMID- 21863763
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment: 4. Role of hematopoietic stem cell transplantation in
      the treatment of lymphoid malignancies].

PMID- 21863764
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: III.
      Diagnosis and treatment; 5. Developmental status and perspective of new drugs for
      lymphoid malignancies in Japan].

PMID- 21863765
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: IV.
      Prognosis and cooperation between hospitals and community clinics; 1. Prognosis
      and prognostic factors in lymphoid malignancy].

PMID- 21863766
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: IV.
      Prognosis and cooperation between hospitals and community clinics; 2. Secondary
      malignancies in malignant lymphoma].

PMID- 21863767
TI  - [Lymphoid malignancies: progress in diagnosis and treatment. Topics: IV.
      Prognosis and cooperation between hospitals and community clinics; 3.
      Comprehensive care of patients with lymphoid malignancies].

PMID- 21863768
TI  - [Discussion meeting on lymphoid malignancies: advances in diagnosis and
      treatment].

PMID- 21863770
TI  - [Case report: a young adult case of poorly differentiated lung adenocarcinoma
      showing the resistance mutation T790M of EGFR before treatment with tyrosine
      kinase inhibitors].

PMID- 21863769
TI  - [Case report: a patient with a six-month history of fever of unknown origin,
      followed by various manifestations of the central nervous system, finally
      diagnosed as having intravascular lymphoma by random skin biopsy].

PMID- 21863771
TI  - [Case report: a case of adult-onset Still's disease with thrombotic
      microangiopathy-like disorder successfully treated by plasma exchange and anti
      TNF therapy].

PMID- 21863772
TI  - [Case report: a case of segmental arterial mediolysis (SAM) with bilateral renal
      infarction, superior mesenteric aneurysm and splenic aneurysm].

PMID- 21863773
TI  - [Case report: a case of cat scratch disease in elderly patient needed to
      differentiate tuberculous lymphadenitis].

PMID- 21863774
TI  - [Case report: a case of pulmonary arteriovenous fistula benefited by
      transcatheter embolotherapy].

PMID- 21863775
TI  - [Case report: a case report of fulminant myocarditis effectively treated by
      concentrated therapy].

PMID- 21863776
TI  - [The cutting-edge of medicine: paradigm shift of diagnosis and treatment of
      rheumatoid arthritis].

PMID- 21863777
TI  - [The cutting-edge of medicine: the educational theory useful for a senior fellow
      of internal medicine].

PMID- 21863778
TI  - [The cutting-edge of medicine: etiology, pathogenesis and treatment in PNH].

PMID- 21863779
TI  - [Knowledge of emergency required for internist: acute respiratory failure].

PMID- 21863780
TI  - [Let's think--clinical quiz (question): thirty-four year-old man with an abnormal
      electrocardiogram in the medical examination].

PMID- 21863781
TI  - [Clinical study from Japan and its reflections: evaluation of the prospective
      observation of erythropoietin--administration for the treatment of acute
      myocardial infarction (EPO/AMI-1) study].

PMID- 21863782
TI  - [Clinical study from Japan and its reflections: j-Cypher Registry].

PMID- 21863783
TI  - [Career development of women fellows of Japanese Society of Internal Medicine.
      Results of the questionnaire survey].

PMID- 21863785
TI  - [Diagnosis at a glance].

PMID- 21863787
TI  - Palladium-catalyzed cross-coupling of sterically demanding boronic acids with
      alpha-bromocarbonyl compounds.
AB  - A catalyst system generated in situ from Pd(dba)(2) and tri(o-tolyl)phosphine
      mediates the coupling of arylboronic acids with alkyl alpha-bromoacetates under
      formation of arylacetic acid esters at unprecedented low loadings. The new
      protocol, which involves potassium fluoride as the base and catalytic amounts of
      benzyltriethylammonium bromide as a phase transfer catalyst, is uniquely
      effective for the synthesis of sterically demanding arylacetic acid derivatives.

PMID- 21863788
TI  - Crystal water molecules as magnetic tuners in molecular metamagnets exhibiting
      antiferro-ferro-paramagnetic transitions.
AB  - We studied the effects of the number of crystal water molecules on the magnetic
      behavior of {[Ni(en)(2)](3)[Fe(CN)(6)](2).xH(2)O}(n) (1-3) (where en =
      ethylenediamine and x = 3, 2, or 0) coordination polymers by (57)Fe Mossbauer
      spectroscopy, single-crystal X-ray diffraction, and magnetization measurements.
      Magnetic phase diagrams constructed for all three compounds indicate that they
      behave as metamagnets exhibiting very rare field-induced antiferro-ferro
      paramagnetic transitions. The number of crystal water molecules has a major
      effect on the Neel temperature, critical field, and magnetic hardness of the
      compounds in the ferromagnetic state. Moreover, the systems behave as molecular
      magnetic sponges, changing their magnetic properties due to the controllable and
      reversible dehydration/hydration process.

PMID- 21863786
TI  - Crystallographic trapping of heme loss intermediates during the nitrite-induced
      degradation of human hemoglobin.
AB  - Heme is an important cofactor in a large number of essential proteins and is
      often involved in small molecule binding and activation. Loss of heme from
      proteins thus negatively affects the function of these proteins but is also an
      important component of iron recycling. The characterization of intermediates that
      form during the loss of heme from proteins has been problematic, in a large part,
      because of the instability of such intermediates. We have characterized, by X-ray
      crystallography, three compounds that form during the nitrite-induced degradation
      of human alpha(2)beta(2) hemoglobin (Hb). The first is an unprecedented complex
      that exhibits a large beta heme displacement of 4.8 A toward the protein
      exterior; the heme displacement is stabilized by the binding of the distal His
      residue to the heme Fe, which in turn allows for the unusual binding of an
      exogenous ligand on the proximal face of the heme. We have also structurally
      characterized complexes that display regiospecific nitration of the heme at the 2
      vinyl position; we show that heme nitration is not a prerequisite for heme loss.
      Our results provide structural insight into a possible pathway for nitrite
      induced loss of heme from human Hb.

PMID- 21863789
TI  - From simple to complex: topological evolution and luminescence variation in a
      copper(I) pyridylpyrazolate system tuned via second ligating spacers.
AB  - By systematically varying the geometric length and electronic properties of the
      second ligating ligands of halogen (Cl(-), Br(-), and I(-)) and pseudohalogen
      (CN(-), SCN(-), and N(3)(-)) anions, we synthesized 11 isomeric/isostructural
      copper(I) complexes: [Cu(2)(L3-3)I](n) (1), [Cu(2)(L4-4)Br](n) (2-Br), [Cu(2)(L4
      4)Cl](n) (2-Cl), [Cu(2)(L3-4)(CN)](n) (3), [Cu(2)(L3-3)(CN)](n) (4), [Cu(3)(L4
      4)(CN)(2)](n) (5), {[Cu(2)(L4-4)Br](2).CuBr}(n) (6-Br), {[Cu(2)(L4
      4)Cl](2).CuCl}(n) (6-Cl), [Cu(2)(L4-4)(SCN)](n) (7alpha-SCN), [Cu(2)(L4
      4)(SCN)](n) (7beta-SCN), and [Cu(2)(L4-4)(N(3))](n) (7alpha-N(3)). These
      structures are based on a series of isomeric pyridylpyrazole ligands, namely, 3,5
      bis(3-pyridyl)-1H-pyrazole (HL3-3), 3-(3-pyridyl)-5-(4-pyridyl)-1H-pyrazole (HL3
      4), and 3,5-bis(4-pyridyl)-1H-pyrazole (HL4-4), and their structural features
      range from 1-D (1), 2-D (2), and 3-D noninterpenetration (3), to 3-D 2-fold
      interpenetration (4 and 5), to 3-D self-catenation (6 and 7), exhibiting a trend
      from simple to complex with dimension expansion and an interpenetrating degree
      increase. The five most complex structures (6 and 7) with self-catenated networks
      are based on 2-fold interpenetrated networks linked via appropriate second
      ligating spacers (Cl(-), Br(-), SCN(-), and N(3)(-)), representing a strategy to
      construct self-catenated coordination polymers through cross-linking
      interpenetrated frameworks. Moreover, these complexes exhibit strong
      photoluminescence, which is mainly ascribed to Cu(I)-related charge transfers
      (MLCT, MC, and MMLCT) regulated by the electronic properties of halogen or
      pseudohalogen. The topological evolution and luminescence variation presented in
      this work open an avenue to understanding the luminescence origin and the
      structure-property relationship of luminescent coordination polymers.

PMID- 21863790
TI  - DABCO as a dynamic hinge between cofacial porphyrin panels and its tumbling
      inside a supramolecular cavity.
AB  - The heteroleptic supramolecular double-decker porphyrin 1 was synthesized with
      DABCO as a guest between two cofacial porphyrin units as characterized by (1)H
      NMR and ESI-MS. While DABCO is not seen to tumble inside the cavity, even at
      higher temperatures (80  degrees C), such motion was triggered upon addition of
      various coordinating ligands (quinuclidine, 4-bromopyridine, or excess of DABCO).
      Different stoichiometric amounts were needed depending on the n donor quality of
      the added ligands to initiate tumbling of the "inside" DABCO. As demonstrated in
      an example with excess DABCO, the tumbling was stopped by lowering the
      temperature to -50  degrees C.

PMID- 21863791
TI  - NMR shielding constants in PH3, absolute shielding scale, and the nuclear
      magnetic moment of 31P.
AB  - Ab initio values of the absolute shielding constants of phosphorus and hydrogen
      in PH(3) were determined, and their accuracy is discussed. In particular, we
      analyzed the relativistic corrections to nuclear magnetic resonance (NMR)
      shielding constants, comparing the constants computed using the four-component
      Dirac-Hartree-Fock approach, the four-component density functional theory (DFT),
      and the Breit-Pauli perturbation theory (BPPT) with nonrelativistic Hartree-Fock
      or DFT reference functions. For the equilibrium geometry, we obtained sigma(P) =
      624.309 ppm and sigma(H) = 29.761 ppm. Resonance frequencies of both nuclei were
      measured in gas-phase NMR experiments, and the results were extrapolated to zero
      density to provide the frequency ratio for an isolated PH(3) molecule. This
      ratio, together with the computed shielding constants, was used to determine a
      new value of the nuclear magnetic dipole moment of (31)P: MU(P) = 1.1309246(50)
      MU(N).

PMID- 21863793
TI  - Synthesis of subphthalocyanines as probes for the accessibility of silica
      nanochannels.
AB  - The synthesis of a new subphthalocyanine is reported. Its structural and
      photophysical properties are ideal for probing the accessibility of arrays of
      silica nanochannels.

PMID- 21863794
TI  - A colorimetric and ratiometric fluorescent probe for palladium.
AB  - A colorimetric and ratiometric fluorescent probe for the palladium species has
      been developed based on the Pd(0)-catalyzed cleavage of an allyoxycarbonyl group
      of amines under mild conditions. The probe displays a highly sensitive and
      selective response with significant changes in both color (from colorless to jade
      green) and fluorescence (from blue to green), through the ICT process.

PMID- 21863796
TI  - Effect of polymer structure on micelles formed between siRNA and cationic block
      copolymer comprising thiols and amidines.
AB  - Small interfering RNA (siRNA) has great therapeutic potential for the suppression
      of proteins associated with disease, but delivery methods are needed for improved
      efficacy. Here, we investigated the properties of micellar siRNA delivery
      vehicles prepared with poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL)
      comprising lysine amines modified to contain amidine and thiol functionality.
      Lysine modification was achieved using 2-iminothiolane (2-IT) [yielding PEG-b
      PLL(N2IM-IM)] or dimethyl 3,3'-dithiobispropionimidate (DTBP) [yielding PEG-b
      PLL(MPA)], with modifications aimed to impart disulfide cross-linking ability
      without compromising cationic charge. These two lysine modification reagents
      resulted in vastly different chemistry contained in the reacted block copolymer,
      which affected micelle formation behavior and stability along with in vitro and
      in vivo performance. Amidines formed with 2-IT were unstable and rearranged into
      a noncharged ring structure lacking free thiol functionality, whereas amidines
      generated with DTBP were stable. Micelles formed with siRNA and PEG-b-PLL(N2IM
      IM) at higher molar ratios of polymer/siRNA, while PEG-b-PLL(MPA) produced
      micelles only near stoichiometric molar ratios. In vitro gene silencing was
      highest for PEG-b-PLL(MPA)/siRNA micelles, which were also more sensitive to
      disruption under disulfide-reducing conditions. Blood circulation was most
      improved for PEG-b-PLL(N2IM-IM)/siRNA micelles, with a circulation half-life 3*
      longer than naked siRNA. Both micelle formulations are promising for siRNA
      delivery applications in vitro and in vivo.

PMID- 21863795
TI  - Individual organelle pH determinations of magnetically enriched endocytic
      organelles via laser-induced fluorescence detection.
AB  - The analysis of biotransformations that occur in lysosomes and other endocytic
      organelles is critical to studies on intracellular degradation, nutrient
      recycling, and lysosomal storage disorders. Such analyses require bioactive
      organelle preparations that are devoid of other contaminating organelles.
      Commonly used differential centrifugation techniques produce impure fractions and
      may not be compatible with microscale separation platforms. Density gradient
      centrifugation procedures reduce the level of impurities but may compromise
      bioactivity. Here we report on simple magnetic setup and a procedure that produce
      highly enriched bioactive organelles based on their magnetic capture as they
      traveled through open tubes. Following capture, in-line laser-induced fluorecence
      detection (LIF) determined for the first time the pH of each magnetically
      retained individual endocytic organelle. Unlike bulk measurements, this method
      was suitable to describe the distributions of pH values in endocytic organelles
      from L6 rat myoblasts treated with dextran-coated iron oxide nanoparticles (for
      magnetic retention) and fluorescein/TMRM-conjugated dextran (for pH measurements
      by LIF). Their individual pH values ranged from 4 to 6, which is typical of
      bioactive endocytic organelles. These analytical procedures are of high relevance
      to evaluate lysosomal-related degradation pathways in aging, storage disorders,
      and drug development.

PMID- 21863797
TI  - Multifunctional chitin nanogels for simultaneous drug delivery, bioimaging, and
      biosensing.
AB  - In this work, we developed biodegradable chitin nanogels (CNGs) by controlled
      regeneration method. For multifunctionalization, we have conjugated CNGs with MPA
      capped-CdTe-QDs (QD-CNGs) for the in vitro cellular localization studies. In
      addition, the Bovine Serum Albumin (BSA) was loaded on to QD-CNGs (BSA-QD-CNGs).
      The CNGs, QD-CNGs, and BSA-QD-CNGs were well-characterized by SEM and AFM, which
      shows that the nanogels are in the range of <100 nm. These were further
      characterized by FT-IR and Cyclic Voltametry. The cytocompatibility assay showed
      that the nanogels are nontoxic to L929, NIH-3T3, KB, MCF-7, PC3, and VERO cells.
      The cell uptake studies of the QD-CNGs were analyzed, which showed retention of
      these nanogels inside the cells (L929, PC3, and VERO). In addition, the protein
      loading efficiency of the nano gels has also been analyzed. Our preliminary
      studies reveal that these multifunctionalized nanogels could be useful for drug
      delivery with simultaneous imaging and biosensing.

PMID- 21863798
TI  - Risk of inundation to coastal wetlands and soil organic carbon and organic
      nitrogen accounting in Louisiana, USA.
AB  - Exceeding 1.2 million acres (4856 km(2)) since the 1930s, coastal wetland loss
      has been the most threatening environmental problem in Louisiana, United States.
      This study utilized high-resolution LiDAR (Light Detection and Ranging) and DEM
      (Digital Elevation Model) data sets to assess the risk of potential wetland loss
      due to future sea level rises, their spatial distribution, and the associated
      loss of soil organic carbon (SOC) and organic nitrogen (SON) estimated from the
      State Soil Geographic (STATSGO) Database and National Wetlands Inventory (NWI)
      digital data. Potential inundation areas were divided into five elevation scales:
      < 0 cm, 0-50 cm, 50-100 cm, 100-150 cm, and 150-200 cm above mean sea level. The
      study found that southeastern Louisiana on the Mississippi River Delta,
      specifically the Pontchartrain and Barataria Basins, are most vulnerable to sea
      level rise induced inundation. Accordingly, approximately 42,264,600 t of SOC and
      2,817,640 t of SON would be inundated by 2050 using an average wetland SOC
      density (203 t per hectare) for the inundation areas between 0 and 50 cm. The
      estimated annual SOC and SON loss from Louisiana's coast is 17% of annual organic
      carbon and 6-8% of annual organic nitrogen inputs from the Mississippi River.

PMID- 21863799
TI  - Cyclopentane-1,3-dione: a novel isostere for the carboxylic acid functional
      group. Application to the design of potent thromboxane (A2) receptor antagonists.
AB  - Cyclopentane-1,3-diones are known to exhibit pK(a) values typically in the range
      of carboxylic acids. To explore the potential of the cyclopentane-1,3-dione unit
      as a carboxylic acid isostere, the physical-chemical properties of representative
      congeners were examined and compared with similar derivatives bearing carboxylic
      acid or tetrazole residues. These studies suggest that cyclopentane-1,3-diones
      may effectively substitute for the carboxylic acid functional group. To
      demonstrate the use of the cyclopentane-1,3-dione isostere in drug design,
      derivatives of a known thromboxane A(2) prostanoid (TP) receptor antagonist, 3-(3
      (2-(4-chlorophenylsulfonamido)ethyl)phenyl)propanoic acid (12), were synthesized
      and evaluated in both functional and radioligand-binding assays. A series of mono
      and disubstituted cyclopentane-1,3-dione derivatives (41-45) were identified
      that exhibit nanomolar IC(50) and K(d) values similar to 12. Collectively, these
      studies demonstrate that the cyclopentane-1,3-dione moiety comprises a novel
      isostere of the carboxylic acid functional group. Given the combination of the
      relatively strong acidity, tunable lipophilicity, and versatility of the
      structure, the cyclopentane-1,3-dione moiety may constitute a valuable addition
      to the palette of carboxylic acid isosteres.

PMID- 21863800
TI  - Tracking hydrogen/deuterium exchange at glycan sites in glycoproteins by mass
      spectrometry.
AB  - Hydrogen/deuterium exchange coupled to mass spectrometry (HDX-MS) has emerged as
      a technique for studying glycoproteins, which are often refractory to classical
      methods. Glycan chains are generally assumed to exchange protons very rapidly,
      making them invisible to this technique. Here, we show that under conditions
      commonly used for HDX-MS, acetamido groups within glycan chains retain a
      significant amount of deuterium. Using mono- and polysaccharide standards along
      with glycopeptides from a panel of glycoproteins, we demonstrate that N-acetyl
      hexosamines, along with modified Asn side chains, are responsible for this
      effect. Model compounds for sialic acid also displayed similar exchange kinetics,
      but terminal sialic acids in the context of an entire glycan chain did not
      contribute to deuterium retention. Furthermore, the presence of sialic acid
      appears to enhance the exchange rate of the nearby N-acetyl glucosamines. The
      ability to detect deuterium exchange at the glycan level opens the possibility of
      applying HDX-MS to monitor glycan interactions and dynamics.

PMID- 21863801
TI  - Mapping irreversible electrochemical processes on the nanoscale: ionic phenomena
      in li ion conductive glass ceramics.
AB  - A scanning probe microscopy approach for mapping local irreversible
      electrochemical processes based on detection of bias-induced frequency shifts of
      cantilevers in contact with the electrochemically active surface is demonstrated.
      Using Li ion conductive glass ceramic as a model, we demonstrate near unity
      transference numbers for ionic transport and establish detection limits for
      current-based and strain-based detection. The tip-induced electrochemical process
      is shown to be a first-order transformation and nucleation potential is close to
      the Li-metal reduction potential. Spatial variability of the nucleation bias is
      explored and linked to the local phase composition. These studies both provide
      insight into nanoscale ionic phenomena in practical Li-ion electrolyte and also
      open pathways for probing irreversible electrochemical, bias-induced, and thermal
      transformations in nanoscale systems.

PMID- 21863792
TI  - Supramolecular coordination: self-assembly of finite two- and three-dimensional
      ensembles.

PMID- 21863802
TI  - Effects of sesamol on apoptosis and steroidogenesis in MA-10 mouse Leydig tumor
      cells.
AB  - Sesamol, a pure compound of sesame, has been reported to have antitumor effects.
      In the present study, the apoptotic and steroidogenic effects of sesamol on MA-10
      cells, a mouse Leydig tumor cell line, was investigated by morphological
      observations, cell viability assay, flow cytometry analysis, radioimmunoassay,
      and immunoblotting assay. We found that the number of rounded-up cells increased
      as the treatment duration of sesamol increased from 3 to 24 h and that the plasma
      membrane blebbing phenomenon could be observed after 12 h of treatment. In the
      cell viability assay, the cell surviving rate significantly decreased as the
      dosage and duration of sesamol treatment increased (p<0.05). Moreover, cell cycle
      studies illustrated that the percentages of subG1 phase cells significantly
      increased after 1 mM sesamol treatments for 12 h, and 0.1 and 1 mM sesamol
      treatments for 24 h, respectively (p<0.05). Furthermore, 0.1 mM sesamol for 24 h
      and 1 mM sesamol for 12 and 24 h treatments, respectively, significantly induced
      the cleavage of caspase-3 (p<0.05). These results confirmed the apoptotic event
      of sesamol treatment on MA-10 cells. Meanwhile, we also found that sesamol at 1
      mM for 24 h and 10 mM for 12 and 24 h significantly increased progesterone
      production (p<0.05), and 1 mM sesamol for 24 h treatment significantly activated
      the expression of steroidogenic acute regulatory (StAR) protein (p<0.05).
      However, the expression of P450scc enzyme remained no different among all
      treatments (p>0.05). In conclusion, sesamol could concurrently induce apoptosis
      through the activation of the caspase pathway and steroidogenesis through the
      induction of StAR protein expression in MA-10 mouse Leydig tumor cells.

PMID- 21863804
TI  - Thermal transport across twin grain boundaries in polycrystalline graphene from
      nonequilibrium molecular dynamics simulations.
AB  - We have studied the thermal conductance of tilt grain boundaries in graphene
      using nonequilibrium molecular dynamics simulations. When a constant heat flux is
      allowed to flow, we observe sharp jumps in temperature at the boundaries,
      characteristic of interfaces between materials of differing thermal properties.
      On the basis of the magnitude of these jumps, we have computed the boundary
      conductance of twin grain boundaries as a function of their misorientation
      angles. We find the boundary conductance to be in the range 1.5 * 10(10) to 4.5 *
      10(10) W/(m(2) K), which is significantly higher than that of any other
      thermoelectric interfaces reported in the literature. Using the computed values
      of boundary conductances, we have identified a critical grain size of 0.1 MUm
      below which the contribution of the tilt boundaries to the conductivity becomes
      comparable to that of the contribution from the grains themselves. Experiments to
      test the predictions of our simulations are proposed.

PMID- 21863803
TI  - Enhanced mechanical rigidity of hydrogels formed from enantiomeric peptide
      assemblies.
AB  - Chirality can be used as a design tool to control the mechanical rigidity of
      hydrogels formed from self-assembling peptides. Hydrogels prepared from
      enantiomeric mixtures of self-assembling beta-hairpins show nonadditive,
      synergistic, enhancement in material rigidity compared to gels prepared from
      either pure enantiomer, with the racemic hydrogel showing the greatest effect. CD
      spectroscopy, TEM, and AFM indicate that this enhancement is defined by nanoscale
      interactions between enantiomers in the self-assembled state.

PMID- 21863805
TI  - Factors affecting phase I stereoselective biotransformation of chiral
      polychlorinated biphenyls by rat cytochrome P-450 2B1 isozyme.
AB  - In vitro incubations of rat cytochrome P-450 (CYP) 2B1 isozyme with three chiral
      polychlorinated biphenyl (PCB) congeners (PCBs 45, 95, and 132) were performed to
      investigate factors affecting phase I stereoselective biotransformation. Rat
      CYP2B1 preferentially biotransformed the second-eluting atropisomers of PCBs 45
      and 95 at low substrate concentration ranges (<=15 MUM). Biotransformation
      competition by different congeners was also observed, with increasing competition
      at higher chlorination. Competition decreased the biotransformation rates of each
      congener stereoselectively, affecting atropisomeric composition. No atropisomeric
      enrichment was observed for PCB 132 upon incubation of the racemate. However,
      under the same conditions, significant differences in biotransformation kinetics
      were observed in individual atropisomer incubations, indicating that (+)-PCB 132
      and (-)-PCB 132 were competitively biotransformed. Homology modeling and docking
      studies suggested that each atropisomer had different interactions with rat
      CYP2B1 and could dock with the isozyme at different locations. This is one
      possible explanation for stereoselective biotransformation and competition of
      chiral PCBs at the molecular level. Our results suggest that the lack of
      predictive capability for stereoselectivity of PCBs and other chiral pollutants
      in biota may be due to competitive and/or inhibitory activities of different
      substrates, including individual enantiomers of the same compound.

PMID- 21863806
TI  - Major issues regarding the efficiency of monitoring programs for nitrate
      contaminated groundwater.
AB  - Major issues regarding the efficiency of moni toring programs for nitrate
      contaminated groundwater are analyzed in this paper: (i) representativeness of
      monitoring networks; (ii) correct interpretation of the monitoring data and
      resulting time series and trends; and (iii) differentiation among the different
      sources of nitrates in groundwater. Following an overview of the nitrate
      contamination problem and possible solutions, as well as some of the difficulties
      found, a relatively straightforward method for assessing monitoring network
      representativity is presented, namely interpolation standard error assessment. It
      is shown how nitrate-concentration time series resulting from periodic
      observations can be corrected with a conservative tracer, in order to avoid
      misinterpretation and confirm or correct apparent trends. Finally, coupled 15N
      and 18O isotope signatures of nitrate (NO3-) in groundwater are used to
      differentiate among nitrogen (N) sources, to ensure correct targeting of
      restoration measures. The case study regards a Nitrate Vulnerable Zone in the
      south of Portugal, designated in compliance with the European Nitrates Directive,
      where coastal discharge of nutrient-rich groundwater threatens the good
      qualitative and ecological status of the Ria Formosa coastal lagoon. Results show
      that mineral fertilizer is the main source of N in groundwater, and that
      increases in N load can be masked by dilution phenomena.

PMID- 21863807
TI  - Biotransformation of nitrosamines and precursor secondary amines under
      methanogenic conditions.
AB  - The biotransformation potential of six nitrosamines and their precursor secondary
      amines by a mixed methanogenic culture was investigated. Among the six
      nitrosamines tested, N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine
      (NMEA), and N-nitrosopyrrolidine (NPYR) were almost completely degraded but only
      when degradable electron donors were available. On the contrary, N
      nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), and N
      nitrosodibutylamine (NDBA) were not degraded. Three precursor secondary amines,
      corresponding to the three biodegradable nitrosamines, were also completely
      utilized even with very low levels of available electron donors. The secondary
      amine precursors of the three, nonbiodegradable nitrosamines were also
      recalcitrant. A bioassay conducted to elucidate the biotransformation pathway of
      NDMA in the mixed methanogenic culture using H(2) as the electron donor showed
      that NDMA was utilized as an electron acceptor and transformed to dimethylamine
      (DMA), which in turn was degraded to ammonia and methane. The H(2) threshold
      concentration for NDMA bioreduction ranged between 0.0017 and 0.031 atm. Such a
      high H(2) threshold concentration suggests that in mixed methanogenic cultures,
      NDMA reducers are weak competitors to other, H(2)-consuming microbial species,
      such as homoacetogens and methanogens. Thus, complete removal of nitrosamines in
      anaerobic digestion systems, where the H(2) partial pressure is typically below
      10(-4) atm, is difficult to achieve.

PMID- 21863808
TI  - A cobalt-dithiolene complex for the photocatalytic and electrocatalytic reduction
      of protons.
AB  - The complex [Co(bdt)(2)](-) (where bdt = 1,2-benzenedithiolate) is an active
      catalyst for the visible light driven reduction of protons from water when
      employed with Ru(bpy)(3)(2+) as the photosensitizer and ascorbic acid as the
      sacrificial electron donor. At pH 4.0, the system exhibits very high activity,
      achieving >2700 turnovers with respect to catalyst and an initial turnover rate
      of 880 mol H(2)/mol catalyst/h. The same complex is also an active
      electrocatalyst for proton reduction in 1:1 CH(3)CN/H(2)O in the presence of weak
      acids, with the onset of a catalytic wave at the reversible redox couple of -1.01
      V vs Fc(+)/Fc. The cobalt-dithiolene complex [Co(bdt)(2)](-) thus represents a
      highly active catalyst for both the electrocatalytic and photocatalytic reduction
      of protons in aqueous solutions.

PMID- 21863809
TI  - Giant phase transition properties at terahertz range in VO2 films deposited by
      sol-gel method.
AB  - VO(2) films were fabricated on high-purity single-crystalline silicon substrate
      by the sol-gel method, followed by rapid annealing. The composition and
      microstructure of the films were investigated by X-ray photoelectron spectroscopy
      (XPS), X-ray diffraction (XRD), field-emission scanning electron microscopy (FE
      SEM), and atomic force microscopy (AFM). The results indicated a polycrystalline
      nature with high crystallinity and compact nanostructure for the films, and the
      concentration of +4 valence vanadium is 79.85%. Correlated with these, a giant
      transmission modulation ratio about 81% of the film was observed by terahertz
      time domain spectroscopy. The experimentally observed transmission
      characteristics were reproduced approximately, by a simulation at different
      conductivities across the phase transition. According to the effective-medium
      theory, we assumed that it is important to increase the concentration of +4
      valence vanadium oxide phases and improve the compactness of the VO(2) films for
      giant phase transition properties. The sol-gel-derived VO(2) films with giant
      phase transition properties at terahertz range, and the study on their
      composition and microstructure, provide considerable insight into the fabrication
      of VO(2) films for the application in THz modulation devices.

PMID- 21863810
TI  - Probing essential nucleobase functional groups in aptamers and deoxyribozymes by
      nucleotide analogue interference mapping of DNA.
AB  - Nucleotide analogue interference mapping of DNA (dNAIM) is here introduced as a
      new nonenzymatic interference-based approach that enables high-throughput
      identification of essential nucleobase functional groups in DNA aptamers and in
      the catalytic core of deoxyribozymes. Nucleobase-modified ribonucleotides are
      statistically incorporated into DNA by solid-phase synthesis, employing the 2'-OH
      group as a chemical tag for analysis of interference effects. This method is
      exemplified on an AMP-binding DNA aptamer and was further used to identify
      indispensable nucleobase functional groups for DNA-catalyzed RNA-ligation by the
      Mg(2+)-dependent deoxyribozymes 7S11 and 9DB1. dNAIM should prove broadly useful
      for facile structural probing of functional DNA for which active and inactive
      variants can be separated based on catalytic or ligand-binding activities.

PMID- 21863811
TI  - Molecular dynamics simulations of water molecule-bridges in polar domains of
      humic acids.
AB  - The stabilizing effect of water molecule bridges on polar regions in humic
      substances (HSs) has been investigated by means of molecular dynamics (MD)
      simulations. The purpose of these investigations was to show the effect of water
      molecular bridges (WAMB) for cross-linking distant locations of hydrophilic
      groups. For this purpose, a tetramer of undecanoid fatty acids connected to a
      network of water molecules has been constructed, which serve as a model for
      spatially fixed aliphatic chains in HSs terminated by a polar (carboxyl) group.
      The effect of environmental polarity has been investigated by using solvents of
      low and medium polarity in force-field MD. A nonpolar environment simulated by n
      hexane was chosen to mimic the stability of WAMB in a hydrophilic hotspot
      surrounded by a nonpolar environment, while the more polar acetonitrile
      environment was chosen to simulate a more even distribution of polarity around
      the carboxylic groups and the water molecules. The dynamics simulations show that
      the rigidity of the oligomer chains is significantly enhanced as soon as the
      water cluster is large enough to comprise all four carboxyl groups. Increasing
      the temperature leads to evaporization processes which destabilize the rigidity
      of the tetramer-water cluster. Embedding it into the nonpolar environment
      introduces a pronounced cage effect which significantly impedes removal of water
      molecules from the cluster region. On the other hand, a polar environment
      facilitates their diffusion from the polar region. One important consequence of
      these simulations is that although the local water network is the stabilizing
      factor for the organic matter matrix, the degree of stabilization is additionally
      affected by the presence of nonpolar surroundings.

PMID- 21863812
TI  - Influence of copper morphology in forming nucleation seeds for graphene growth.
AB  - We report that highly crystalline graphene can be obtained from well-controlled
      surface morphology of the copper substrate. Flat copper surface was prepared by
      using a chemical mechanical polishing method. At early growth stage, the density
      of graphene nucleation seeds from polished Cu film was much lower and the domain
      sizes of graphene flakes were larger than those from unpolished Cu film. At later
      growth stage, these domains were stitched together to form monolayer graphene,
      where the orientation of each domain crystal was unexpectedly not much different
      from each other. We also found that grain boundaries and intentionally formed
      scratched area play an important role for nucleation seeds. Although the best
      monolayer graphene was grown from polished Cu with a low sheet resistance of 260
      Omega/sq, a small portion of multilayers were also formed near the impurity
      particles or locally protruded parts.

PMID- 21863813
TI  - Degradation kinetics and mechanism of antibiotic ceftiofur in recycled water
      derived from a beef farm.
AB  - Ceftiofur is a third-generation cephalosporin antibiotic that has been widely
      used to treat bacterial infections in concentrated animal feeding operations
      (CAFOs). Land application of CAFO waste may lead to the loading of ceftiofur
      residues and its metabolites to the environment. To understand the potential
      contamination of the antibiotic in the environment, the degradation kinetics and
      mechanisms of ceftiofur in solutions blended with and without the recycled water
      derived from a beef farm were investigated. The transformation of ceftiofur in
      aqueous solutions in the presence of the CAFO recycled water was the combined
      process of hydrolysis and biodegradation. The total degradation rates of
      ceftiofur at 15  degrees C, 25  degrees C, 35  degrees C, and 45  degrees C
      varied from 0.4-2.8*10(-3), 1.4-4.4*10(-3), 6.3-11*10(-3), and 11-17*10(-3) h(
      1), respectively, in aqueous solutions blended with 1 to 5% CAFO recycled water.
      Hydrolysis of ceftiofur increased with incubation temperature from 15 to 45 
      degrees C. The biodegradation rates of ceftiofur were also temperature-dependent
      and increased with the application amounts of the recycled CAFO water. Cef
      aldehyde and desfuroylceftiofur (DFC) were identified as the main biodegradation
      and hydrolysis products, respectively. This result suggests that the primary
      biodegradation mechanism of ceftiofur was the cleavage of the beta-lactam ring,
      while hydrolytic cleavage occurred at the thioester bond. Unlike DFC and
      ceftiofur, cef-aldehyde does not contain a beta-lactam ring and has less
      antimicrobial activity, indicating that the biodegradation of ceftiofur in animal
      wastewater may mitigate the potentially adverse impact of the antibiotic to the
      environment.

PMID- 21863814
TI  - Role of positive ions in determining the deposition rate and film chemistry of
      continuous wave hexamethyl disiloxane plasmas.
AB  - New data shed light on the mechanisms of film growth from low power, low pressure
      plasmas of organic compounds. These data rebalance the widely held view that
      plasma polymer formation is due to radical/neutral reactions only and that ions
      play no direct role in contributing mass at the surface. Ion reactions are shown
      to play an important role in both the plasma phase and at the surface. The mass
      deposition rate and ion flux in continuous wave hexamethyl disiloxane (HMDSO)
      plasmas have been studied as a function of pressure and applied RF power. Both
      the deposition rate and ion flux were shown to increase with applied power;
      however, the deposition rate increased with pressure while the ion flux
      decreased. Positive ion mass spectrometry of the plasma phase demonstrates that
      the dominant ionic species is the (HMDSO-CH(3))(+) ion at m/z 147, but
      significant fragmentation and subsequent oligomerization was also observed.
      Chemical analysis of the deposits by X-ray photoelectron spectroscopy and
      secondary ion mass spectrometry show that the deposits were consistent with
      deposits reported by previous workers grown from plasma and hyperthermal (HMDSO
      CH(3))(+) ions. Increasing coordination of silicon with oxygen in the plasma
      deposits reveals the role of ions in the growth of plasma polymers. Comparing the
      calculated film thicknesses after a fixed total fluence of 1.5 * 10(19) ions/m(2)
      to results for hyperthermal ions shows that ions can contribute significantly to
      the total absorbed mass in the deposits.

PMID- 21863815
TI  - Noncovalent interaction of dietary polyphenols with common human plasma proteins.
AB  - Common human plasma proteins (CHPP), also called blood proteins, are proteins
      found in blood plasma. The molecular structure/property-affinity relationships of
      dietary polyphenols noncovalently binding to CHPP were investigated by comparing
      the binding constants obtained from the fluorescence titration method. An
      additional methoxy group in flavonoids increased their binding affinities for
      CHPP by 1.05 to 72.27 times. The hydroxylation on the 4' position (ring B) of
      flavones and flavonols and the 5 position (ring A) of isoflavones weakened the
      binding affinities; however, the hydroxylation on other positions of flavonoids
      slightly enhanced or little affected the binding affinities for CHPP. The
      glycosylation of flavonoids weakened or slightly affected the affinities for CHPP
      by 1 order of magnitude. The hydrogenation of the C2?C3 double bond of flavone, 6
      hydroxyflavone, 6-methoxyflavone and myricetin decreased the binding affinities
      about 10.02 to 17.82 times. The galloylation of catechins significantly improved
      the binding affinities with CHPP about 10 to 1000 times. The esterification of
      gallic acid increased its binding affinity. The binding affinities with CHPP were
      strongly influenced by the structural differences of dietary polyphenols.
      Polyphenols with higher affinities for purified HSA also showed stronger
      affinities with CHPP. The hydrophobic force played an important role in binding
      interaction between polyphenols and CHPP.

PMID- 21863817
TI  - Green synthesis of polycyclic benzimidazole derivatives and organic
      semiconductors.
AB  - Polycyclic benzimidazole derivatives, an important class of compounds in organic
      electronics and photovoltaics, were prepared using a solvent-free "green" process
      based on heating carboxylic acid anhydrides and arylene diamines in the presence
      of zinc acetate in the solid state. Products were isolated and purified directly
      by train sublimation of the crude reaction mixtures. The reaction conditions were
      optimized using various carboxylic acid anhydrides. Optical and electrochemical
      properties of these materials are also described.

PMID- 21863816
TI  - Three-step synthesis of cyclopropyl peptidomimetics.
AB  - An efficient approach to novel cyclopropyl peptidomimetics has been developed.
      The synthetic route involves a cyclopropanation using ethyl
      (dimethylsulfuranylidene)acetate (EDSA) as the key step and affords a cyclopropyl
      peptidomimetic core in three steps from protected amino acid Weinreb amides.

PMID- 21863818
TI  - Alkali metal cation-induced destabilization of gas-phase protein-ligand
      complexes: consequences and prevention.
AB  - Electrospray ionization, now a well established technique for studying
      noncovalent protein-ligand interactions, is prone to production of alkali metal
      adducts. Here it is shown that this adduction significantly destabilizes the
      interactions between two model proteins and their ligands and that
      destabilization correlates with cation size. For both the [FKBP.FK506] and
      [lysozyme.NAG(n)] systems, dissociation of the metalated complex occurs at
      markedly lower collision energies than their purely protonated equivalents.
      Dependency upon size of the metal(+) demonstrates the importance of electrostatic
      charge density during the dissociation process. Differences in the gas phase
      basicities (GBapp) of the multiply charged protein ions and proton and sodium
      affinities of the ligands explain the observed charge partitioning during
      dissociation of the complexes. Ion mobility-mass spectrometry measurements
      demonstrate that metal cation adduction does not induce a significant increase in
      unfolding of the polypeptides, indicating that this is not the principal
      mechanism responsible for destabilization. Destabilizing effects can be largely
      reduced by exposing the electrospray to solvent (e.g., acetonitrile) vapor, a
      method that acts to reduce the amount of adduct formation as well as decrease the
      charge states of the resulting ions. This approach leads to more accurate
      determination of apparent K(D)s in the presence of trace alkali metals.

PMID- 21863819
TI  - Separation of a set of peptide sequence isomers using differential ion mobility
      spectrometry.
AB  - Protein identification in bottom-up proteomics requires disentangling isomers of
      proteolytic peptides, a major class of which are sequence inversions. Their
      separation using ion mobility spectrometry (IMS) has been limited to isomeric
      pairs. Here we demonstrate baseline separation of all seven 8-mer tryptic peptide
      isomers using differential IMS. Evaluation of peak capacity implies that even
      larger libraries should be resolved for heavier peptides with higher charge
      states.

PMID- 21863820
TI  - Sensitive and selective chromogenic sensing of carbon monoxide via reversible
      axial CO coordination in binuclear rhodium complexes.
AB  - The study of probes for CO sensing of a family of binuclear rhodium(II) compounds
      of general formula [Rh(2){(XC(6)H(3))P(XC(6)H(4))}(n)(O(2)CR)(4-n)].L(2)
      containing one or two metalated phosphines (in a head-to-tail arrangement) and
      different axial ligands has been conducted. Chloroform solutions of these
      complexes underwent rapid color change, from purple to yellow, when air samples
      containing CO were bubbled through them. The binuclear rhodium complexes were
      also adsorbed on silica and used as colorimetric probes for "naked eye" CO
      detection in the gas phase. When the gray-purple colored silica solids containing
      the rhodium probes were exposed to air containing increasing concentrations of
      CO, two colors were observed, in agreement with the formation of two different
      products. The results are consistent with an axial coordination of the CO
      molecule in one axial position (pink-orange) or in both (yellow). The crystal
      structure of 3.(CO) ([Rh(2){(C(6)H(4))P(C(6)H(5))(2)}(2)(O(2)CCF(3))(2)].CO) was
      solved by single X-ray diffraction techniques. In all cases, the binuclear
      rhodium complexes studied showed a high selective response to CO with a
      remarkable low detection limit. For instance, compound 5.(CH(3)CO(2)H)(2)
      ([Rh(2){(m-CH(3)C(6)H(3))P(m
      CH(3)C(6)H(4))(2)}(2)(O(2)CCH(3))(2)].(CH(3)CO(2)H)(2)) is capable of detection
      of CO to the "naked eye" at concentrations as low as 0.2 ppm in air. Furthermore,
      the binding of CO in these rhodium complexes was found to be fully reversible,
      and release studies of carbon monoxide via thermogravimetric measurements have
      also been carried out. The importance of the silica support for the maintenance
      of the CO-displaced L ligands in the vicinity of the probes in a noninnocent
      manner has been also proved.

PMID- 21863821
TI  - Crystal structure and function of human nucleoplasmin (npm2): a histone chaperone
      in oocytes and embryos.
AB  - Human Npm2 is an ortholog of Xenopus nucleoplasmin (Np), a chaperone that binds
      histones. We have determined the crystal structure of a truncated Npm2-core at
      1.9 A resolution and show that the N-terminal domains of Npm2 and Np form similar
      pentamers. This allowed us to model an Npm2 decamer which may be formed by
      hydrogen bonds between quasi-conserved residues in the interface between two
      pentamers. Interestingly, the Npm2 pentamer lacks a prototypical A1-acidic tract
      in each of its subunits. This feature may be responsible for the inability of
      Npm2-core to bind histones. However, Npm2 with a large acidic tract in its C
      terminal tail (Npm2-A2) is able to bind histones and form large complexes.
      Fluorescence resonance energy transfer experiments and biochemical analysis of
      loop mutations support the premise that nucleoplasmins form decamers when they
      bind H2A-H2B dimers and H3-H4 tetramers simultaneously. In the absence of histone
      tetramers, these chaperones bind H2A-H2B dimers with a single pentamer forming
      the central hub. When taken together, our data provide insights into the
      mechanism of histone binding by nucleoplasmins.

PMID- 21863823
TI  - Fluorescent small molecule probe to modulate and explore alpha2beta1 integrin
      function.
AB  - Collagen binding integrins are an important family of cell surface receptors that
      mediate bidirectionally signals between the interior of the cell and the
      extracellular matrix. The protein-protein interactions between cells and collagen
      are necessary for many physiological functions, but also promote diseases. For
      example, the interaction of alpha2beta1 integrin and collagen has been shown to
      have an important role in thrombus formation and cancer spread. The fact that the
      discovery of small molecules that can block such protein-protein interactions is
      highly challenging has significantly hindered the discovery of pharmaceutical
      agents to treat these diseases. Here, we present a rationally designed novel
      fluorescent molecule that can be synthesized in just a few minutes from
      commercially available starting materials. This molecule blocks the protein
      protein interaction between alpha2beta1 integrin and collagen, and due to its
      fluorescent properties, it can be employed in wide variety of biological
      applications.

PMID- 21863822
TI  - Searching and optimizing structure ensembles for complex flexible sugars.
AB  - NMR restrictions are suitable to specify the geometry of a molecule when a single
      well-defined global free energy minimum exists that is significantly lower than
      other local minima. Carbohydrates are quite flexible, and therefore, NMR
      observables do not always correlate with a single conformer but instead with an
      ensemble of low free energy conformers that can be accessed by thermal
      fluctuations. In this communication, we describe a novel procedure to identify
      and weight the contribution to the ensemble of local minima conformers based on
      comparison to residual dipolar couplings (RDCs) or other NMR observables, such as
      scalar couplings. A genetic algorithm is implemented to globally minimize the R
      factor comparing calculated RDCs to experiment. This is done by optimizing the
      weights of different conformers derived from the exhaustive local minima
      conformational search program, fast sugar structure prediction software (FSPS).
      We apply this framework to six human milk sugars, LND-1, LNF-1, LNF-2, LNF-3,
      LNnT, and LNT, and are able to determine corresponding population weights for the
      ensemble of conformers. Interestingly, our results indicate that in all cases the
      RDCs can be well represented by only a few most important conformers. This
      confirms that several, but not all of the glycosidic linkages in histo-blood
      group "epitopes" are quite rigid.

PMID- 21863824
TI  - Melting and crystallization of ice in partially filled nanopores.
AB  - We investigate the melting and formation of ice in partially filled hydrophilic
      and hydrophobic nanopores of 3 nm diameter using molecular dynamics simulations
      with the mW water model. Above the melting temperature, the partially filled
      nanopores contain two water phases in coexistence: a condensed liquid plug and a
      surface-adsorbed phase. It has been long debated in the literature whether the
      surface-adsorbed phase is involved in the crystallization. We find that only the
      liquid plug crystallizes on cooling, producing ice I with stacks of hexagonal and
      cubic layers. The confined ice is wetted by a premelted liquid layer that
      persists in equilibrium with ice down to temperatures well below its melting
      point. The liquid-ice transition is first-order-like but rounded. We determine
      the temperature and enthalpy of melting as a function of the filling fraction of
      the pore. In agreement with experiments, we find that the melting temperature of
      the nanoconfined ice is strongly depressed with respect to the bulk T(m), it
      depends weakly on the filling fraction and is insensitive to the hydrophobicity
      of the pore wall. The state of water in the crystallized hydrophilic and
      hydrophobic pores, however, is not the same: the hydrophobic pore has a
      negligible density of the surface-adsorbed phase and higher fraction of water in
      the ice phase than the hydrophilic pore. The widths of the ice cores are
      nevertheless comparable for the hydrophobic and hydrophilic pores, and this may
      explain their almost identical melting temperatures. The enthalpy of melting
      DeltaH(m), when normalized by the actual amount of ice in the pore, is
      indistinguishable for the hydrophobic and hydrophilic pores, insensitive to the
      filling fraction, and within the error bars, the same as the difference in
      enthalpy between bulk liquid and bulk ice evaluated at the temperature of melting
      of ice in the nanopores.

PMID- 21863825
TI  - Geminate charge recombination in liquid alkane with concentrated CCl4: effects of
      CCl4 radical anion and narrowing of initial distribution of Cl-.
AB  - Dynamics of radical cations and electrons in an admixture of a linear saturated
      hydrocarbon (n-dodecane) and halocarbon (carbon tetrachloride, CCl(4)) were
      investigated by picosecond electron beam pulse radiolysis. The decay of
      thermalized electrons (e(th)(-)) observed in infrared transient photoabsorption
      were simply accelerated by the addition of CCl(4), giving a high rate constant of
      2.3 * 10(11) mol(-1) dm(3) s(-1). The decrease of the initial yield of e(th)(-)
      was quantified by C(37) (50 mmol), which is linked to the reaction of epithermal
      electrons (e(-)) with CCl(4). In contrast, the n-dodecane radical cation
      (RH(2)(*+)) monitored in the near-infrared indicated a convex-type dependence of
      the decay rate on CCl(4) concentration, although the initial yield of RH(2)(*+)
      remained almost constant up to a much higher CCl(4) concentration. The decay of
      RH(2)(*+) was analyzed by Monte Carlo simulations of geminate ion recombination
      with e(th)(-), chlorine anion (Cl(-)) formed via dissociative electron
      attachment, and CCl(4) radical anion. The results showed a good agreement with
      the experiments by considering two assumptions: (1) CCl(4) radical anion formed
      via e(th)(-) attachment and (2) narrowing of the initial distribution of Cl(-).
      The decrease in the initial yield of RH(2)(*+) at high CCl(4) concentration was
      well explained by immediate decomposition of CCl(4)(*+) to CCl(3)(+) and hole
      transfer from CCl(4)(*+) to adjacent RH(2) without diffusive motion of the
      reactants. Time-dependent density functional theory supported the spectroscopic
      assignment of intermediate species in the n-dodecane/CCl(4) system. The present
      results would be of help in understanding the electron capture reaction in
      multicomponent systems such as a chemically amplified resist in lithography.

PMID- 21863826
TI  - Preparation and characterization of mono- and multilayer films of polymerizable
      1,2-polybutadiene using the Langmuir-Blodgett technique.
AB  - The essence of this study is to apply the Langmuir-Blodgett (LB) technique for
      assembling asymmetric membranes. Accordingly, Langmuir films of a (further)
      polymerizable polymer, 1,2-polybutadiene (1,2-pbd), were studied and transferred
      onto different solid supports, such as gold, indium tin oxide (ITO), and silicon.
      The layers were characterized both at the air/water interface as well as on
      different substrates using numerous methods including cyclic voltammetry,
      impedance spectroscopy, spectroscopic ellipsometry, atomic force microscopy, X
      ray photoelectron spectroscopy, and reflection-absorption Fourier transform
      infrared spectroscopy. The Langmuir films were stable at the air-water interface
      as long as they were not exposed to UV irradiation. The LB films formed
      disorganized layers, which gradually blocked the permeation of different species
      with increasing the number of deposited layers. The thickness was ca. 4-7 A per
      layer. Irradiating the Langmuir films caused their cross-linking at the air-water
      interface. Furthermore, we took advantage of the reactivity of the double bond of
      the LB films on the solid supports and graft polymerized acrylic acid on top of
      the 1,2-pbd layers. This approach is the basis of the formation of an asymmetric
      membrane that requires different porosity on both of its sides.

PMID- 21863827
TI  - Pan-arctic river fluxes of polychlorinated biphenyls.
AB  - Observations of polychlorinated biphenyls (PCB) concentrations in fluvial surface
      sediments near the mouths of the six Great Arctic Rivers (GARs; Ob, Yenisey,
      Lena, Indigirka, Kolyma, and Mackenzie) were combined with annual dissolved
      organic carbon (DOC) and particulate organic carbon (POC) loadings and hydraulic
      discharge to estimate the pan-Arctic river flux of PCBs. The highest total-phase
      fluxes of ?(13)PCB were found for the Ob River, with 184 kg/yr and the smallest
      for the Indigirka River with 3.9 kg/yr. Consistent with a continent-scale trend
      among the Eurasian GARs of increasing POC concentrations eastward, which is
      extending to the North American Mackenzie River, a general shift in the estimated
      PCB partitioning from dissolved to particle-associated flux was found toward the
      east. Pentachlorinated and hexachlorinated PCBs constituted the majority (>70%)
      of the total PCB fluxes in the Eurasian Rivers. In contrast, trichlorinated and
      tetrachlorinated congeners were the most abundant in the Mackenzie (~ 75%). The
      total ?(13)PCB fluxes from the pan-Arctic rivers are here estimated to be ~0.4
      tonne/yr. This is geochemically consistent with the inventory of total PCBs in
      the Polar Mixed Layer of the entire Arctic Ocean (0.39 tonne) and about a factor
      2 less than two new estimates of the PCB settling export to Arctic subsurface
      waters. Hence, the yearly Great Arctic River PCB fluxes only represent 0.001% of
      the historical PCB emission into the global environment. To our knowledge, this
      is the first estimate of circum-Arctic river flux of any organic pollutant based
      on a comprehensive investigation of the pollutants in several rivers and it
      contributes toward a more complete understanding of large-scale contaminant
      cycling in the Arctic.

PMID- 21863828
TI  - Characterizing the molecular order of phosphonic acid self-assembled monolayers
      on indium tin oxide surfaces.
AB  - Self-assembled monolayers (SAMs) of alkanephosphonic acids with chain lengths
      between 8 and 18 carbon units were formed on thin films of indium tin oxide (ITO)
      sputter-deposited on silicon substrates with 400 nm thermally grown SiO(2). The
      silicon substrates, while not intended for use in near-IR or visible optics
      applications, do provide smooth surfaces that permit systematic engineering of
      grain size and surface roughness as a function of the sputter pressure. Argon
      sputter pressures from 4 to 20 mTorr show systematic changes in surface
      morphology ranging from smooth, micrometer-sized grain structures to <50 nm
      grains with 3* higher surface roughness. Near-edge X-ray absorption fine
      structure (NEXAFS) spectroscopy experiments are conducted for alkanephosphonic
      acids deposited on these wide range of ITO surfaces to evaluate the effects of
      these morphological features on monolayer ordering. Results indicate that long
      chain SAMs are more highly ordered, and have a smaller tilt angle, than short
      chain SAMs. Surprisingly, the 1-octadecyl phosphonic acids maintain their order
      as the lateral grain dimensions of the ITO surface shrink to ~50 nm. It is only
      when the ITO surface roughness becomes greater than the SAM chain length (~15 A)
      that SAMs are observed to become relatively disordered.

PMID- 21863829
TI  - Theoretical prediction of the spin-spin coupling constants between an axis and
      macrocycle of a rotaxane.
AB  - The indirect nuclear spin-spin coupling constants between nuclei belonging to the
      axis and to the macrocycle of three structurally related rotaxanes have been
      calculated by means of density functional theory. It has been shown that the
      through-space axis-macrocycle proton-proton coupling constants can be as large as
      0.4-0.5 Hz and therefore of measurable values. The largest through-space axis
      macrocycle carbon-proton and nitrogen-proton coupling constants are 0.2-0.3 Hz.
      Visualization of coupling pathways by means of the coupling energy density method
      indicates that the larger proton-proton couplings are indeed transmitted through
      the space between the coupled nuclei. Thus, it seems that measurement of such
      couplings should be possible and that indirect spin-spin couplings can be
      actually transmitted through-space, with no covalent or hydrogen bonds between
      the coupled nuclei.

PMID- 21863830
TI  - Steric-effect induced alterations in streaming potential and energy transfer
      efficiency of non-newtonian fluids in narrow confinements.
AB  - In this work, we explore the possibilities of utilizing the combined consequences
      of interfacial electrokinetics and rheology toward augmenting the energy transfer
      efficiencies in narrow fluidic confinements. In particular, we consider the
      exploitation of steric effects (i.e., effect of finite size of the ionic species)
      in non-Newtonian fluids over small scales, to report dramatic augmentations in
      the streaming potential, for shear-thickening fluids. We first derive an
      expression for the streaming potential considering strong electrical double layer
      interactions in the confined flow passage and the consequences of the finite
      conductance of the Stern layer, going beyond the Debye-Huckel limit. With a
      detailed accounting for the excluded volume effects of the ionic species and
      their interaction with pertinent interfacial phenomena of special type of
      rheological fluids such as the power law fluids in the above-mentioned formalism,
      we demonstrate that a confluence of the steric interactions with the non
      Newtonian transport characteristics may result in giant augmentations in the
      energy transfer efficiency for shear-thickening fluids under appropriate
      conditions.

PMID- 21863831
TI  - Thermal and mechanical aging of self-assembled monolayers as studied by near edge
      X-ray absorption fine structure.
AB  - Self-assembled monolayers (SAMs) enable significant changes in the surface energy
      and/or specific interactions of surfaces, which are desirable for
      microelectromechanical systems (MEMS), superhydrophobic coatings, sensors, and
      other applications. However, SAMs often exhibit poor durability and rapid
      degradation upon mechanical, thermal, or moisture exposure. The chemical and
      orientational changes in SAMs due to mechanical and thermal degradation were
      investigated using near-edge X-ray absorption fine structure (NEXAFS) and the
      water contact angle. SAMs were based on unfluorinated or fluorinated linear
      hydrocarbons that form highly oriented and densely packed structures on silicon
      substrates. Complex chemical and orientational changes were observed via NEXAFS
      following degradation. Under heating in a dry, oxygen-rich environment,
      unfluorinated SAMs tended to cleave at C-C bonds on the main chain; below 250 
      degrees C, CH(3) groups were sequentially cleaved toward the surface, whereas
      above 250  degrees C, remaining hydrocarbon groups were converted to a graphitic
      coating dominated by C?C bonds. Under similar conditions, fluorinated SAMs began
      their chemical degradation at 350  degrees C and above, although the orientation
      decreased steadily from 150 to 300  degrees C; at and above 350  degrees C, the
      preferential removal of F occurred and the SAM was slowly converted to a
      graphitic layer. By contrast, under vacuum the fluorinated molecules were very
      thermally stable, showing good stability up to 550  degrees C; when degradation
      occurred, entire molecules were removed. Mechanical degradation followed two
      routes; both unfluorinated and fluorinated SAMs that were mechanically rubbed
      with smooth surfaces exhibited severe chemical degradation of the molecules,
      leading to an amorphous and poorly defined layer with C?C, C-C, C-H, and C-F
      bonds. Unfluorinated and fluorinated surfaces that were mechanically rubbed in
      the presence of free silicon particulates showed the rapid and complete
      destruction of both the molecular orientation and the protective SAM layer, even
      for short exposure periods. The resulting NEXAFS spectra were very similar to
      those produced by heating to 550  degrees C, suggesting that the friction created
      by granular particles may lead to extreme local heating.

PMID- 21863832
TI  - Influence of surfactant structure on reverse micelle size and charge for nonpolar
      electrophoretic inks.
AB  - Electrophoretic inks, which are suspensions of colorant particles that are
      controllably concentrated and dispersed by applied electric fields, are the
      leading commercial technology for high-quality reflective displays. Extending the
      state of the art for high-fidelity color in these displays requires improved
      understanding and control of the colloidal systems. In these inks, reverse
      micelles in nonpolar media play key roles in media and particle charging. Here we
      investigate the effect of surfactant structure on reverse micelle size and
      charging properties by synthesizing different surfactants with variations in
      polyamine polar head groups. Small-angle X-ray scattering (SAXS) and dynamic
      light scattering (DLS) were used to determine the micelle core plus shell size
      and micelle hydrodynamic radius, respectively. The results from SAXS agreed with
      DLS and showed that increasing polyamines in the surfactant head increased the
      micelle size. The hydrodynamic radius was also calculated on the basis of
      transient current measurements and agreed well with the DLS results. The
      transient current technique further determined that increasing polyamines
      increased the charge stabilization capability of the micelles and that an
      analogous commercial surfactant OLOA 11000 made for a lower concentration of
      charge-generating ions in solution. Formulating magenta inks with the various
      surfactants showed that the absence of amine in the surfactant head was
      detrimental to particle stabilization and device performance.

PMID- 21863833
TI  - Slow dissociation of a charged ligand: analysis of the primary quinone Q(A) site
      of photosynthetic bacterial reaction centers.
AB  - Reaction centers (RCs) are integral membrane proteins that undergo a series of
      electron transfer reactions during the process of photosynthesis. In the Q(A)
      site of RCs from Rhodobacter sphaeroides, ubiquinone-10 is reduced, by a single
      electron transfer, to its semiquinone. The neutral quinone and anionic
      semiquinone have similar affinities, which is required for correct in situ
      reaction thermodynamics. A previous study showed that despite similar affinities,
      anionic quinones associate and dissociate from the Q(A) site at rates ~10(4)
      times slower than neutral quinones indicating that anionic quinones encounter
      larger binding barriers (Madeo, J.; Gunner, M. R. Modeling binding kinetics at
      the Q(A) site in bacterial reaction centers. Biochemistry 2005, 44, 10994-11004).
      The present study investigates these barriers computationally, using steered
      molecular dynamics (SMD) to model the unbinding of neutral ground state
      ubiquinone (UQ) and its reduced anionic semiquinone (SQ(-)) from the Q(A) site.
      In agreement with experiment, the SMD unbinding barrier for SQ(-) is larger than
      for UQ. Multi Conformational Continuum Electrostatics (MCCE), used here to
      calculate the binding energy, shows that SQ(-) and UQ have comparable affinities.
      In the Q(A) site, there are stronger binding interactions for SQ(-) compared to
      UQ, especially electrostatic attraction to a bound non-heme Fe(2+). These
      interactions compensate for the higher SQ(-) desolvation penalty, allowing both
      redox states to have similar affinities. These additional interactions also
      increase the dissociation barrier for SQ(-) relative to UQ. Thus, the slower SQ(
      ) dissociation rate is a direct physical consequence of the additional binding
      interactions required to achieve a Q(A) site affinity similar to that of UQ. By a
      similar mechanism, the slower association rate is caused by stronger interactions
      between SQ(-) and the polar solvent. Thus, stronger interactions for both the
      unbound and bound states of charged and highly polar ligands can slow their
      binding kinetics without a conformational gate. Implications of this for other
      systems are discussed.

PMID- 21863835
TI  - Molecular doping of porous organic cages.
AB  - Porous organic cages can act as hosts for the three-dimensional alignment of
      guests such as halogens and organometallics. Porous single crystals are doped by
      vapor sublimation to produce diamondoid arrangements of guests such as I(5)(-)
      and OsO(4), leading to marked conductivity enhancement in the case of I(5)(-).

PMID- 21863834
TI  - Biocompatible drug delivery system for photo-triggered controlled release of 5
      Fluorouracil.
AB  - The synthesis of a photo-triggered biocompatible drug delivery system on the
      basis of coumarin-functionalized block copolymers is reported. The coumarin
      functionalized block copolymers poly(ethylene oxide)-b-poly(n-butyl methacrylate
      co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin)) (PEO-b-P(BMA- co-CMA)) were
      synthesized via atom transfer radical polymerization (ATRP). The micelle-drug
      conjugates were made by covalent bonding of anticancer drug 5-fluorouracil (5-FU)
      to the coumarin under UV irradiation at wavelength >310 nm. These micelle-drug
      conjugates possessed spherical morphology with diameters of 70 nm from TEM
      images. In vitro drug release experiments showed the controlled release of
      anticancer drug 5-FU from the micelle-drug conjugates under UV irradiation (254
      nm). These micelle-drug conjugates also showed excellent biocompatibility by the
      in vitro cytotoxicity experiments. The results suggest that these micelle-drug
      conjugates could be a promising candidate for the delivery of anticancer agents
      with low side effects on normal cells and excellent therapeutic efficacy to
      cancer cells.

PMID- 21863837
TI  - Local virial and tensor theorems.
AB  - We show that for any wave function and potential the local virial theorem can
      always be satisfied 2K(r) = r.DeltaV by choosing a particular expression for the
      local kinetic energy. In addition, we show that for each choice of local kinetic
      energy there are an infinite number of quasi-probability distributions which will
      generate the same expression. We also consider the local tensor virial theorem.

PMID- 21863836
TI  - Biosynthesis and characterization of polyhydroxyalkanoate block copolymer P3HB-b
      P4HB.
AB  - Polyhydroxyalkanoates (PHA) synthesis genes phbC and orfZ cloned from Ralstonia
      eutropha H16 were transformed into beta-oxidation weakened Pseudomonas putida
      KTOY08DeltaGC, a mutant of P. putida KT2442. The recombinant P. putida strain
      termed KTHH06 was able to produce a short-chain-length PHA block copolymer
      consisting of poly(3-hydroxybutyrate) (P3HB) as one block and poly(4
      hydroxybutyrate) (P4HB) as another block. One-dimensional and two-dimensional
      nuclear magnetic resonance (NMR) clearly indicated the polymer was a diblock
      copolymer consisting of 20 mol % P3HB as one block and 80 mol % P4HB as another
      one. Differential scanning calorimetric (DSC) showed that P3HB block melting
      temperatures (T(m)) in the block copolymer P3HB-b-P4HB was shift to low
      temperature compared with homopolymer P3HB and a blend of P3HB and P4HB. The
      block copolymer with a number average molecular weight of 50000 Da and a
      polydispersity of 3.1 demonstrated a better yield and tensile strength compared
      with that of its related random copolymer and blend of homopolymers of P3HB and
      P4HB.

PMID- 21863838
TI  - An improved palladium-catalyzed conversion of aryl and vinyl triflates to
      bromides and chlorides.
AB  - A facile Pd-catalyzed conversion of aryl and vinyl triflates to aryl and vinyl
      halides (bromides and chlorides) is described. This method allows convenient
      access to a variety of aryl, heteroaryl, and vinyl halides in good to excellent
      yields and with greatly simplified conditions relative to our previous report.

PMID- 21863839
TI  - Gibbs free energy of liquid drops on conical fibers.
AB  - Small drops can move spontaneously on conical fibers. As a drop moves along the
      cone, it must change shape to maintain a constant volume, and thus, it must
      change its surface energy. Simultaneously, the exposed surface area of the
      underlying cone must also change. The associated surface energies should balance
      each other, and the drop should stop moving when it reaches a location where the
      free energy is a minimum. In this paper, a minimum Gibbs free energy analysis has
      been performed to predict where a drop will stop on a conical fiber. To obtain
      the Gibbs free energies of a drop at different locations of a conical fiber, the
      theoretical expressions for the shape of a droplet on a conical fiber are derived
      by extending Carroll's equations for a drop on a cylindrical fiber. The predicted
      Gibbs free energy exhibits a minimum along the length of the cone. For a constant
      cone angle, as the contact angle between the liquid and the cone increases, the
      drop will move toward the apex of the cone. Likewise, for a constant contact
      angle, as the cone angle increases, the drop moves toward the apex. Experiments
      in which water and dodecane were placed on glass cones verify these dependencies.
      Thus, the final location of a drop on a conical fiber can be predicted on the
      basis of the geometry and surface energy of the cone, the surface tension and
      volume of the liquid, and the original location where the drop was deposited.

PMID- 21863840
TI  - Ligand-passivated Eu:Y2O3 nanocrystals as a phosphor for white light emitting
      diodes.
AB  - Eu(III)-doped Y(2)O(3) nanocrystals are prepared by microwave synthetic methods
      as spherical 6.4 +/- 1.5 nm nanocrystals with a cubic crystal structure. The
      surface of the nanocrystal is passivated by acetylacetonate (acac) and HDA on the
      Y exposed facet of the nanocrystal. The presence of acac on the nanocrystal
      surface gives rise to a strong S(0) -> S(1) (pi -> pi*, acac) and acac -> Ln(3+)
      ligand to metal charge transfer (LMCT) transitions at 270 and 370 nm,
      respectively, in the Eu:Y(2)O(3) nanocrystal. Excitation into the S(0) -> S(1)
      (pi -> pi*) or acac -> Ln(3+) LMCT transition leads to the production of white
      light emission arising from efficient intramolecular energy transfer to the
      Y(2)O(3) oxygen vacancies and the Eu(III) Judd-Ofelt f-f transitions. The acac
      passivant is thermally stable below 400  degrees C, and its presence is evidenced
      by UV-vis absorption, FT-IR, and NMR measurements. The presence of the low-lying
      acac levels allows UV LED pumping of the solid phosphor, leading to high quantum
      efficiency (~19%) when pumped at 370 nm, high-quality white light color rendering
      (CIE coordinates 0.33 and 0.35), a high scotopic-to-photopic ratio (S/P = 2.21),
      and thermal stability. In a LED lighting package luminosities of 100 lm W(-1)
      were obtained, which are competitive with current commercial lighting technology.
      The use of the passivant to funnel energy to the lanthanide emitter via a
      molecular antenna effect represents a new paradigm for designing phosphors for
      LED-pumped white light.

PMID- 21863841
TI  - Change in electronic states in the accumulation layer at interfaces in a poly(3
      hexylthiophene) field-effect transistor and the impact of encapsulation.
AB  - The electrical properties of organic field-effect transistors (OFETs) are largely
      determined by the accumulation layer that extends only a few molecular layers
      away from the gate dielectric/organic semiconductor interface. To understand
      degradation processes that occur within the device structure under ambient
      conditions, it is thus essential to probe the interface using an architecture
      that minimizes the effects of bulk transport of contaminating species through
      upper layers of material in a thick film device. Using FETs designed with
      multiple voltage probes along the conducting channel and an ultrathin film of the
      active material, we found that the charge carrier density and the FET mobility
      decrease, and further, the contact and channel properties are strongly
      correlated. FET devices prepared with an ultrathin film of P3HT become
      significantly contact limited in air due to a hole diffusion barrier near the
      drain electrode. Encapsulation of the device with a layered organic/inorganic
      barrier material consisting of parylene and Al(2)O(3) appreciably retarded
      diffusion of molecular species from ambient air into P3HT.

PMID- 21863842
TI  - Mechanistic investigations of cooperative catalysis in the enantioselective
      fluorination of epoxides.
AB  - This report describes mechanistic studies of the (salen)Co- and amine-cocatalyzed
      enantioselective ring opening of epoxides by fluoride. The kinetics of the
      reaction, as determined by in situ (19)F NMR analysis, are characterized by
      apparent first-order dependence on (salen)Co. Substituent effects, nonlinear
      effects, and reactivity with a linked (salen)Co catalyst provide evidence for a
      rate-limiting, bimetallic ring-opening step. To account for these divergent data,
      we propose a mechanism wherein the active nucleophilic fluorine species is a
      cobalt fluoride that forms a resting-state dimer. Axial ligation of the amine
      cocatalyst to (salen)Co facilitates dimer dissociation and is the origin of the
      observed cooperativity. On the basis of these studies, we show that significant
      improvements in the rates, turnover numbers, and substrate scope of the fluoride
      ring-opening reactions can be realized through the use of a linked salen
      framework. Application of this catalyst system to a rapid (5 min) fluorination to
      generate the unlabeled analog of a known PET tracer, F-MISO, is reported.

PMID- 21863843
TI  - Structure of micelles of a nonionic block copolymer determined by SANS and SAXS.
AB  - The micellar state of Pluronic P123, which is a poly(ethylene oxide)-b
      poly(propylene oxide)-b- poly(ethylene oxide) block polymer (EO(20)PO(70)EO(20)),
      has been investigated using SANS, SAXS, and differential scanning calorimetry
      under the conditions utilized in the synthesis of ordered mesoporous materials,
      such as SBA-15. The absolute intensity measurements, both with SANS and SAXS,
      have provided a detailed quantitative description of the P123 micelles in the
      framework of a simple core-shell spherical model. The model developed has been
      used to establish the structure of the copolymer micelles, including their size,
      shape, aggregation number and detailed composition, as well as the structural
      changes induced by varying reaction conditions. The effects of temperature, pH,
      acidic source and the addition of swelling agents (toluene and TMB) are reported
      and discussed.

PMID- 21863845
TI  - Highly stereoselective synthesis of 1,2,3-trisubstituted indanes via oxidative N
      heterocyclic carbene-catalyzed cascades.
AB  - Three stereocenters are formed in the carbene catalyzed cascade reaction of enals
      with various beta-diketones to give the corresponding indane derivatives with
      excellent stereoselectivities. The products are readily transformed to the
      corresponding 1,2,3-trisubstituted indane derivatives, which represent privileged
      substructures in medicinal chemistry.

PMID- 21863844
TI  - Kinetics of the formation of 2D-hexagonal silica nanostructured materials by
      nonionic block copolymer templating in solution.
AB  - The different steps of the self-assembly in solution of several 2D-hexagonal
      silica nanostructured SBA-15 materials have been investigated by SAXS and SANS in
      situ experiments. Unique quantitative information about the shape and size
      evolution upon time of the micellar aggregates throughout the self-assembly
      process is obtained using a complete model that describes well the scattering
      data for the various synthesis conditions. In all cases, before the precipitation
      of the material, the micelles shape changes from spherical to rod-like, where the
      structure of the rod-like micelles is linked to the structure of the 2D-hexagonal
      precipitated material. In addition, the kinetics of hydrolysis of the inorganic
      precursor (TEOS) has been determined by in situ Raman spectroscopy. More
      specifically, by comparing synthesis made with different acids (HNO(3), HBr, HCl,
      H(2)SO(4), and H(3)PO(4)), it is found that materials prepared using the "salting
      out" anions (SO(4)(2-) and H(2)PO(4)(-)) are much better ordered than with the
      "salting-in" anions (NO(3)(-) and Br(-)).

PMID- 21863846
TI  - "Two-in-one" fabrication of Fe3O4/MePEG-PLA composite nanocapsules as a potential
      ultrasonic/MRI dual contrast agent.
AB  - A new method for the fabrication of Fe(3)O(4) nanoparticles enveloped by
      polymeric nanocapsules is proposed. This method is characterized by combining a
      double emulsification with the interfacial coprecipitation of iron salts to form
      Fe(3)O(4)/polymer composite nanocapsules in a single step. To demonstrate the
      viability of this approach, methoxy poly(ethylene glycol)-poly(lactide) (MePLEG)
      was chosen as the shell material for Fe(3)O(4)/MePLEG nanocapsules. In addition
      to the versatility offered for fabricating nanocapsules with different shell
      materials, the method was found to be convenient for adjusting the magnetite
      content of the nanocapsules from 0 to 43%. In addition to their confirmed T(2)
      weighted magnetic resonance imaging (MRI) enhancement, the resultant composite
      nanocapsules display much more obvious acoustic responses than MePLEG
      nanocapsules in an acoustic investigation. Furthermore, the low toxicity of these
      composite nanocapsules, as confirmed by our study, combined with their magnetic
      and acoustic properties ensure that these composite nanocapsules have great
      potential in acting as ultrasonic/MRI dual contrast agents.

PMID- 21863847
TI  - Ceramic coatings of LA141 alloy formed by plasma electrolytic oxidation for
      corrosion protection.
AB  - Superlight Mg-Li alloy is a promising structural materials in aerospace,
      automobile, and electronics because of its excellent properties such as low
      density, high ductility, superior strength-to-weight ratio, and good damping
      ability. The fabrication of compact plasma electrolytic oxidation coatings with
      excellent corrosion resistance is valuable for the widespread application of Mg
      Li alloy. Here we present a ceramic coating on the surface of Mg-14Li-1Al (LA141)
      alloy for corrosion protection via plasma electrolytic oxidation (PEO) in an
      alkaline silicate electrolyte with tungstate as an additive. X-ray photoelectron
      spectroscopy and thin film-X-ray diffraction analysis of coatings show that the
      surface coating is mainly comprised of Mg(2)SiO(4), MgO and WO(3). Scanning
      electron microscopy observations have revealed that the dense and compact coating
      formed in the presence of tungstate has less structural imperfections in
      comparison to the control one fabricated without use of tungstate. The effect of
      oxidation time on the morphology and phase composition of coatings is also
      examined in detail.

PMID- 21863848
TI  - Ionic specificity in pH regulated charged interfaces: Fe3+ versus La3+.
AB  - We determine the distribution of two trivalent ions Fe(3+) and La(3+) next to two
      different amphiphilic charged interfaces as ions or complexes, consisting of the
      phosphate lipid dihexadecyl phosphate (DHDP) and the fatty acid arachidic acid
      (AA). These amphiphiles provide a wide range of pK(a) values, from 2.1 (DHDP) to
      5.1 (AA), thus allowing manipulation of the surface charge over extremely low pH
      (pH ~1 or larger), and the two ions provide two limiting cases of specificity for
      the amphiphiles. We find that La(3+) distribution is mostly sensitive to the
      surface charge, whereas the Fe(3+) binding depends on its character in the
      solution and is highly specific, as indicated by the crucial role played by iron
      complexes (Fe(OH)(3) or Fe(OH)(2+)) forming covalent bonds even for an uncharged
      interface. The implications of the results to other ions and/or amphiphilic
      interfaces are also discussed.

PMID- 21863849
TI  - An abiotic fluorescent probe for cardiac troponin I.
AB  - The first ratiometric fluorescent reporter was designed for the detection of
      cardiac troponin I (cTnI), a key protein elicited during cardiac muscle cell
      death. In designing this abiotic fluorescent probe, docking simulation studies
      were performed to predict the probe/protein interactions along the solvent
      exposed regions of cTnI. Simple cuvette titration experiments in aqueous buffered
      solution indicate remarkable selectivity for cardiac troponin in the clinically
      relevant nM region versus skeletal troponin.

PMID- 21863850
TI  - Spectroelectrochemical investigation of intramolecular and interfacial electron
      transfer rates reveals differences between nitrite reductase at rest and during
      turnover.
AB  - A combined fluorescence and electrochemical method is described that is used to
      simultaneously monitor the type-1 copper oxidation state and the nitrite turnover
      rate of a nitrite reductase (NiR) from Alcaligenes faecalis S-6. The catalytic
      activity of NiR is measured electrochemically by exploiting a direct electron
      transfer to fluorescently labeled enzyme molecules immobilized on modified gold
      electrodes, whereas the redox state of the type-1 copper site is determined from
      fluorescence intensity changes caused by Forster resonance energy transfer (FRET)
      between a fluorophore attached to NiR and its type-1 copper site. The
      homotrimeric structure of the enzyme is reflected in heterogeneous interfacial
      electron-transfer kinetics with two monomers having a 25-fold slower kinetics
      than the third monomer. The intramolecular electron-transfer rate between the
      type-1 and type-2 copper site changes at high nitrite concentration (>=520 MUM),
      resulting in an inhibition effect at low pH and a catalytic gain in enzyme
      activity at high pH. We propose that the intramolecular rate is significantly
      reduced in turnover conditions compared to the enzyme at rest, with an exception
      at low pH/nitrite conditions. This effect is attributed to slower reduction rate
      of type-2 copper center due to a rate-limiting protonation step of residues in
      the enzyme's active site, gating the intramolecular electron transfer.

PMID- 21863851
TI  - Ultrafast dynamics of nonequilibrium resonance energy transfer and probing
      globular protein flexibility of myoglobin.
AB  - Protein structural plasticity is critical to many biological activities and
      accurate determination of its temporal and spatial fluctuations is challenging
      and difficult. Here, we report our extensive characterization of global
      flexibility of a globular heme protein of myoglobin using resonance energy
      transfer as a molecular ruler. With site-directed mutagenesis, we use a
      tryptophan scan to examine local structural fluctuations from B to H helices
      utilizing 10 tryptophan-heme energy transfer pairs with femtosecond resolution.
      We observed ultrafast resonance energy transfer dynamics by following a nearly
      single exponential behavior in 10-100 ps, strongly indicating that the globular
      structure of myoglobin is relatively rigid, with no observable static or slow
      dynamic conformational heterogeneity. The observation is against our molecular
      dynamics simulations, which show large local fluctuations and give multiple
      exponential energy transfer behaviors, suggesting too flexible of the global
      structure and thus raising a serious issue of the force fields used in
      simulations. Finally, these ultrafast energy transfer dynamics all occur on the
      similar time scales of local environmental relaxations (solvation), leading to
      nonexponential processes caused by energy relaxations, not structural
      fluctuations. Our analyses of such processes reveal an intrinsic compressed-
      and/or stretched-exponential behaviors and elucidate the nature of inherent
      nonequilibrium of ultrafast resonance energy transfer in proteins. This new
      concept of compressed nonequilibrium transfer dynamics should be applied to all
      protein studies by time-resolved Forster resonance energy transfer (FRET).

PMID- 21863852
TI  - Experimental and theoretical charge density studies at subatomic resolution.
AB  - Analysis of accurate experimental and theoretical structure factors of diamond
      and silicon reveals that the contraction of the core shell due to covalent bond
      formation causes significant perturbations of the total charge density that
      cannot be ignored in precise charge density studies. We outline that the nature
      and origin of core contraction/expansion and core polarization phenomena can be
      analyzed by experimental studies employing an extended Hansen-Coppens multipolar
      model. Omission or insufficient treatment of these subatomic charge density
      phenomena might yield erroneous thermal displacement parameters and high residual
      densities in multipolar refinements. Our detailed studies therefore suggest that
      the refinement of contraction/expansion and population parameters of all atomic
      shells is essential to the precise reconstruction of electron density
      distributions by a multipolar model. Furthermore, our results imply that also the
      polarization of the inner shells needs to be adopted, especially in cases where
      second row or even heavier elements are involved in covalent bonding. These
      theoretical studies are supported by direct multipolar refinements of X-ray
      powder diffraction data of diamond obtained from a third-generation synchrotron
      radiation source (SPring-8, BL02B2).

PMID- 21863853
TI  - Bisphosphonamidate clodronate prodrug exhibits potent anticancer activity in non
      small-cell lung cancer cells.
AB  - Bisphoshonates are used clinically to treat disorders of calcium metabolism,
      hypercalcemia and osteoporosis, and malignant bone disease. Although these agents
      are commonly used in cancer patients and have potential direct anticancer
      effects, their use for the treatment of extraskeletal disease is limited as a
      result of poor cellular uptake. We have designed and synthesized
      bisphosphonamidate prodrugs that undergo intracellular activation to release the
      corresponding bisphosphonate and require only two enzymatic activation events to
      unmask multiple negative charges. We demonstrate efficient bisphosphonamidate
      activation and significant enhancement in anticancer activity of two
      bisphosphonamidate prodrugs in vitro compared to the parent bisphosphonate. These
      data suggest a novel approach to optimizing the anticancer activities of commonly
      used bisphosphonates.

PMID- 21863854
TI  - Do temporal and geographical patterns of HBCD and PBDE flame retardants in U.S.
      fish reflect evolving industrial usage?
AB  - Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) are
      common flame retardants in polymers and textiles. Recognition of the persistent,
      bioaccumulative, and toxic properties of PBDEs has prompted reductions in their
      use. In contrast, HBCD has received less scrutiny. The U.S has historically been
      a dominant BFR consumer. However, the few publications on HBCD in wildlife here
      suggest modest levels compared to Asian and European studies. In contrast, the
      HBCD concentrations we detected in U.S. fish are among the highest reported in
      the world. The temporal trends observed suggest that HBCD use may have risen, and
      that of Penta-BDE declined, following the 2004 termination of its U.S.
      manufacture. For example, Hyco River carp collected in 1999-2002 exhibited a mean
      ?HBCD (sum of alpha-, beta- and gamma-HBCD) concentration of only 13 ng/g (lipid
      weight basis), but was 4640 ng/g in fish collected in 2006-2007. In contrast, the
      mean ?PBDE level in these same fish decreased from 40,700 ng/g in 1999-2002 to
      9140 ng/g in 2006-2007. Concentrations of HBCD and PBDEs in several Hyco River
      fish species exceeded those from rivers less influenced by manufacturing
      outfalls. Results support the contention that textile-related production,
      relative to its BFR market share, may release disproportionately large amounts of
      HBCD to the environment.

PMID- 21863855
TI  - Very large, soluble endohedral fullerenes in the series La2C90 to La2C138:
      isolation and crystallographic characterization of La2@D5(450)-C100.
AB  - An extensive series of soluble dilanthanum endohedral fullerenes that extends
      from La(2)C(90) to La(2)C(138) has been discovered. The most abundant of these,
      the nanotubular La(2)@D(5)(450)-C(100), has been isolated in pure form and
      characterized by single-crystal X-ray diffraction.

PMID- 21863856
TI  - Competitive inhibition of heparinase by persulfonated glycosaminoglycans: a tool
      to detect heparin contamination.
AB  - Heparin and the low molecular weight heparins are extensively used as medicinal
      products to prevent and treat the formation of venous and arterial thrombi. In
      early 2008, administration of some heparin lots was associated with the advent of
      severe adverse effects, indicative of an anaphylactoid-like response. Application
      of orthogonal analytical tools enabled detection and identification of the
      contaminant as oversulfated chondroitin sulfate (OSCS) was reported in our
      earlier report. Herein, we investigate whether enzymatic depolymerization using
      the bacterially derived heparinases, given the structural understanding of their
      substrate specificity, can be used to identify the presence of OSCS in heparin.
      We also extend this analysis to examine the effect of other persulfonated
      glycosaminoglycans (GAGs) on the action of the heparinases. We find that all
      persulfonated GAGs examined were effective inhibitors of heparinase I, with
      IC(50) values ranging from approximately 0.5-2 MUg/mL. Finally, using this
      biochemical understanding, we develop a rapid, simple assay to assess the purity
      of heparin using heparinase digestion followed by size-exclusion HPLC analysis to
      identify and quantify digestion products. In the context of the assay, we
      demonstrate that less than 0.1% (w/w) of OSCS (and other persulfonated
      polysaccharides) can routinely be detected in heparin.

PMID- 21863857
TI  - Metal-mediated tandem coassembly of collagen peptides into banded
      microstructures.
AB  - The ability to recapitulate the features of natural collagen at the micro- and
      nanoscale with novel biopolymers has the potential to lead to improved
      biomaterials. Herein we describe stimuli-responsive collagen-based peptides
      (IdaCol and HisCol) that together form higher order assemblies in the presence of
      added metal ions. SEM and TEM imaging of these assemblies revealed microscale
      petal-like and intertwined fiber morphologies, each with periodic banding on the
      nanometer scale. The observed banding is consistent with tandem coassembly of
      alternating IdaCol and HisCol triple helical blocks that may laterally associate
      either in or out of register to form higher order structures, and mimics the
      banding found in natural collagen fibers.

PMID- 21863859
TI  - An n-channel two-dimensional covalent organic framework.
AB  - Co-condensation of metallophthalocyanine with an electron-deficient
      benzothiadiazole (BTDA) block leads to the formation of a two-dimensional
      covalent organic framework (2D-NiPc-BTDA COF) that assumes a belt shape and
      consists of AA stacking of 2D polymer sheets. Integration of BTDA blocks at the
      edges of a tetragonal metallophthalocyanine COF causes drastic changes in the
      carrier-transport mode and a switch from a hole-transporting skeleton to an
      electron-transporting framework. 2D-NiPc-BTDA COF exhibits broad and enhanced
      absorbance up to 1000 nm, shows panchromatic photoconductivity, is highly
      sensitive to near-infrared photons, and has excellent electron mobility as high
      as 0.6 cm(2) V(-1) s(-1).

PMID- 21863860
TI  - A microporous hydrogen-bonded organic framework for highly selective C2H2/C2H4
      separation at ambient temperature.
AB  - The first microporous hydrogen-bonded organic framework with permanent porosity
      and exhibiting extraordinarily highly selective adsorptive separation of C(2)H(2)
      and C(2)H(4) at ambient temperature has been established.

PMID- 21863858
TI  - Does compound I vary significantly between isoforms of cytochrome P450?
AB  - The cytochrome P450 (CYP) enzymes are important in many areas, including
      pharmaceutical development. Subtle changes in the electronic structure of the
      active species, Compound I, have been postulated previously to account partly for
      the experimentally observed differences in reactivity between isoforms. Current
      predictive models of CYP metabolism typically assume an identical Compound I in
      all isoforms. Here we present a method to calculate the electronic structure and
      to estimate the Fe-O bond enthalpy of Compound I, and apply it to several human
      and bacterial CYP isoforms. Conformational flexibility is accounted for by
      sampling large numbers of structures from molecular dynamics simulations, which
      are subsequently optimized with density functional theory (B3LYP) based quantum
      mechanics/molecular mechanics. The observed differences in Compound I between
      human isoforms are small: They are generally smaller than the spread of values
      obtained for the same isoform starting from different initial structures. Hence,
      it is unlikely that the variation in activity between human isoforms is due to
      differences in the electronic structure of Compound I. A larger difference in
      electronic structure is observed between the human isoforms and P450(cam) and may
      be explained by the slightly different hydrogen-bonding environment surrounding
      the cysteinyl sulfur. The presence of substrate in the active site of all
      isoforms studied appears to cause a slight decrease in the Fe-O bond enthalpy,
      apparently due to displacement of water out of the active site, suggesting that
      Compound I is less stable in the presence of substrate.

PMID- 21863861
TI  - Effects of self-assembled materials prepared from V2O5 for lithium ion
      electroinsertion.
AB  - Self-assembled materials consisting of V(2)O(5), polyallylamine (PAH) and silver
      nanoparticles (AgNPs) were obtained by the layer-by-layer (LbL) method, aiming at
      their application as electrodes for lithium-ion batteries and electrochromic
      devices. The method employed herein allowed for linear growth of visually
      homogeneous films composed of V(2)O(5), V(2)O(5)/PAH, and V(2)O(5)/PAH/AgNP with
      15 bilayers. According to the Fourier transform infrared spectra, interaction
      between the oxygen atom of the vanadyl group and the amino group should be
      responsible for the growth of these films. This interaction also enabled
      establishment of an electrostatic shield between the lithium ions and the sites
      with higher negative charge, thereby raising the ionic mobility and consequently
      increasing the energy storage capacity and reducing the response time. According
      to the site-saturation model and the electrochemical and spectroelectrochemical
      results, the presence of PAH in the self-assembled host matrix decreased the
      number of V(2)O(5) electroactive sites. Thus, AgNPs were stabilized in PAH and
      inserted into the nanoarchitecture, so as to enhance the specific capacity. This
      should provide new conducting pathways and connect isolated V(2)O(5) particles in
      the host matrix. Therefore, new nanoarchitectures for specific interactions were
      formed spontaneously and chosen as examples in this work, aiming to demonstrate
      the potentiality of the adopted self-assembled method for enhancing the charge
      transport rate into the host matrices. The obtained materials displayed suitable
      properties for use as electrodes in lithium batteries and electrochromic devices.

PMID- 21863862
TI  - Photoswitching-induced frequency-locked donor-acceptor fluorescence double
      modulations identify the target analyte in complex environments.
AB  - Precisely identifying biological targets and accurately extracting their
      relatively weak signals from complicated physiological environments represent
      daunting challenges in biological detection and biomedical diagnosis.
      Fluorescence techniques have become the method of choice and offer minimally
      invasive and ultrasensitive detections, thus, providing a wealth of information
      regarding the biological mechanisms in living systems. Despite fluorescence
      analysis has advanced remarkably, conventional detections still encounter
      considerable limitations. This stems from the fact that the fluorescence
      intensity signal (I) is sensitive and liable to numerous external factors
      including temperature, light source, medium characteristics, and dye
      concentration. The interferences exasperatingly undermine the precision of
      measurements, and frequently render the signal undetectable. For example,
      fluorescence from single-molecule emitters can be measured on glass substrates
      under optimum conditions, but single-molecule events in complicated physiological
      environments such as live cells can hardly be detected because of
      autofluorescence interference and other factors. Furthermore, traditional
      intensity (I) and wavelength (lambda) measurements do not reveal the interactive
      nature between the donor and the acceptor. Thus, innovative detection strategies
      to circumvent these aforementioned limitations of the conventional techniques are
      critically needed. With the use of photoswitching-induced donor-acceptor
      fluorescence double modulations, we present a novel strategy that introduces
      three additional physical parameters: modulation amplitude (A), phase shift
      (DeltaPhi), and lock-in frequency (omega), and demonstrate that such a strategy
      can circumvent the limitation of the conventional fluorescence detection
      techniques. Together, these five physical quantities (I, lambda, A, DeltaPhi,
      omega) reveal insightful information regarding molecular interactive strength
      between the probe and the analyte and enable extracting weak-fluorescence spectra
      from large interfering noises in complex environments.

PMID- 21863863
TI  - Formation of Ag nanoparticle-doped foam-like polymer films at the liquid-liquid
      interface.
AB  - The composite poly(2-vinylpyridine) (P2VP)-Ag(+) foam-like thin films were
      prepared at the interface between AgNO(3) aqueous solution and polymer chloroform
      solution at 25  degrees C. An X-ray photoelectron spectroscopy (XPS)
      investigation indicated that Ag(+) ions in the composite films were partially
      transformed to Ag atoms after irradiated by UV-light and completely transformed
      to Ag atoms after being treated with KBH(4) aqueous solution. Ag nanoparticles
      with the average sizes of 2.71 +/- 0.82 and 3.28 +/- 1.20 nm were generated in
      these two transferred films with different treatments, respectively. Transmission
      electron microscopy (TEM) and high-resolution TEM (HRTEM) images showed clearly
      that the composite films were composed of microcapsules whose walls had
      multilayer structures, and the nanoparticles were incorporated in the walls. The
      formation of the composite films at the liquid-liquid interface was attributed to
      the adsorption of the polymer molecules at the interface, coordination between
      the pyridine groups and Ag(+) ions, and self-assembly of the composite molecules.
      Furthermore, the catalytic activity of the composite films was evaluated using
      the reduction of 4-nitrophenol (4-NP) by KBH(4). The results demonstrated that
      the composite thin films have high and durable catalytic activity.

PMID- 21863864
TI  - DSX: a knowledge-based scoring function for the assessment of protein-ligand
      complexes.
AB  - We introduce the new knowledge-based scoring function DSX that consists of
      distance-dependent pair potentials, novel torsion angle potentials, and newly
      defined solvent accessible surface-dependent potentials. DSX pair potentials are
      based on the statistical formalism of DrugScore, extended by a much more
      specialized set of atom types. The original DrugScore-like reference state is
      rather unstable with respect to modifications in the used atom types. Therefore,
      an important method to overcome this problem and to allow for robust results when
      deriving pair potentials for arbitrary sets of atom types is presented. A
      validation based on a carefully prepared test set is shown, enabling direct
      comparison to the majority of other popular scoring functions. Here, DSX features
      superior performance with respect to docking- and ranking power and runtime
      requirements. Furthermore, the beneficial combination with torsion angle
      dependent and desolvation-dependent potentials is demonstrated. DSX is robust,
      flexible, and capable of working together with special features of popular
      docking engines, e.g., flexible protein residues in AutoDock or GOLD. The program
      is freely available to the scientific community and can be downloaded from our
      Web site  www.agklebe.de .

PMID- 21863865
TI  - Development of catalytically active silver colloid nanoparticles stabilized by
      dextran.
AB  - Colloidal silver nanoparticles (Ag-NPs) with a mean diameter of 6.1 nm and a
      narrow size distribution were prepared by reduction of the correspondent metal
      salt with injection of NaBH(4), in the presence of dextran, and characterized by
      UV-vis, TEM, and DLS. The concentration of all reactants involved in the
      formation of the nanoparticles was optimized with the use of a new multivariate
      method, which revealed a significant reduction in the number of experiments when
      compared with the vast majority of univariate methods described in the
      literature. The Ag-NPs-dextran composite was able to efficiently catalyze the p
      nitrophenol reduction in water by NaBH(4) with a rate constant normalized to the
      surface area of the nanoparticles per unit volume (k(1)) of 1.41 s(-1) m(-2) L,
      which is higher than values ever reported for Ag-NPs catalytic systems.

PMID- 21863866
TI  - Fabrication of super-oil-repellent dual pillar surfaces with optimized pillar
      intervals.
AB  - Hierarchical dual pillar surfaces with optimized pillar intervals are fabricated
      by a novel combined process of the oblique angle magnetron sputtering deposition
      of Al-Nb alloys and their anodizing. The pillar intervals are controlled by the
      deposition angle and cell size of a scalloped substrate for oblique angle
      deposition. Anodizing of the deposited pillar surfaces develops a nanopillar
      oxide layer, producing the hierarchical dual pillar surfaces. After being coated
      with a fluoroalkyl phosphate layer to reduce the surface free energy,
      hierarchical surfaces with submicrometer pillar intervals greater than 400 nm
      show super liquid repellency even for hexadecane with a low surface tension of
      27.5 mN m(-1), although the submicrometer pillar surfaces with smaller
      submicrometer pillar intervals and without nanopillars were not super-oil
      repellent. In contrast, the dual pillar surfaces show superhydrophobicity
      regardless of the submicrometer pillar intervals. Thus, the present study
      demonstrates the importance of the pillar intervals (gap size between pillars) to
      realize the superoleophobicity.

PMID- 21863867
TI  - Liquid crystal droplets as a hosting and sensing platform for developing
      immunoassays.
AB  - In this paper, we report an immunoassay in which probe proteins are immobilized
      on the surface of liquid crystal (LC) droplets rather than on solid surfaces. The
      advantage of this immunoassay is that the binding of antibodies to the probe
      proteins can be transduced by the LC droplets directly without the need for
      additional steps. For example, when we incubate the LC droplets decorated with
      immunoglobulin G (IgG) in a solution containing anti-IgG (AIgG), these droplets
      change their orientations from radial to bipolar configuration. In contrast, when
      we incubate the IgG-LC droplets in a solution containing anti-human serum albumin
      (AHSA), no changes are observed. The change of orientational configuration
      indicates the formation of the antigen-antibody immunocomplex on the surface of
      the LC droplets. Using LC droplet immunoassays, we successfully detect antibody
      concentrations as low as 0.01 MUg/mL for AIgG and 0.02 MUg/mL for AHSA. Because
      the immunoassay using LC droplets is label-free and gives a unique optical
      response, it has the potential to be further developed as a portable and low-cost
      immunoassay.

PMID- 21863868
TI  - Charge delocalization in a cyclometalated bisruthenium complex bridged by a
      noninnocent 1,2,4,5-tetra(2-pyridyl)benzene ligand.
AB  - Two ruthenium atoms are covalently connected to the para positions of a phenyl
      ring in 1,2,4,5-tetra(2-pyridyl)benzene (tpb) to form a linear Ru-tpb-Ru
      arrangement. This unique structure leads to appealing electronic properties for
      the biscyclometalated complex [(tpy)Ru(tpb)Ru(tpy)](2+), where tpy is 2,2';6',2"
      terpyridine. It could be stepwise oxidized at substantially low potential (+0.12
      and +0.55 V vs Ag/AgCl) and with a noticeably large comproportionation constant
      (1.94 * 10(7)). In addition to the routinely observed metal-to-ligand charge
      transfer transitions, [(tpy)Ru(tpb)Ru(tpy)](2+) displays a separate and distinct
      absorption band at 805 nm with appreciable absorptivity (epsilon = 9000 M(-1) cm(
      1)). This band is assigned to the charge transition from the Ru-tpb-Ru motif to
      the pyridine rings of tpb with the aide of density functional theory (DFT) and
      time-dependent DFT calculations. Complex [(tpy)Ru(tpb)Ru(tpy)](2+) was precisely
      titrated with 1 equiv of cerium ammonium nitrate to produce
      [(tpy)Ru(tpb)Ru(tpy)](3+), which shows intense multiple NIR transitions. The
      electronic coupling parameters H(ab) of individual NIR components are determined
      to be 5812, 4942, 4358, and 3560 cm(-1). DFT and TDDFT calculation were performed
      on [(tpy)Ru(tpb)Ru(tpy)](3+) to elucidate its electronic structure and spin
      density population and the nature of the observed NIR transitions. Electron
      paramagnetic resonance studies of [(tpy)Ru(tpb)Ru(tpy)](3+) exhibit a discernible
      rhombic signal with the isotropic g factor of ?g? = 2.144. These results point to
      the strong orbital interaction of tpb with metal centers and that tpb behaves as
      a redox noninnocent bridging ligand in [(tpy)Ru(tpb)Ru(tpy)](2+). Complex
      [(tpy)Ru(tpb)Ru(tpy)](3+) is determined to be a Robin-Day class III system with
      full charge delocalization across the Ru-tpb-Ru motif.

PMID- 21863869
TI  - Hydride-induced amplification of performance and binding enthalpies in chromium
      hydrazide gels for Kubas-type hydrogen storage.
AB  - Hydrogen is the ideal fuel because it contains the most energy per gram of any
      chemical substance and forms water as the only byproduct of consumption. However,
      storage still remains a formidable challenge because of the thermodynamic and
      kinetic issues encountered when binding hydrogen to a carrier. In this study, we
      demonstrate how the principal binding sites in a new class of hydrogen storage
      materials based on the Kubas interaction can be tuned by variation of the
      coordination sphere about the metal to dramatically increase the binding
      enthalpies and performance, while also avoiding the shortcomings of hydrides and
      physisorpion materials, which have dominated most research to date. This was
      accomplished through hydrogenation of chromium alkyl hydrazide gels, synthesized
      from bis(trimethylsilylmethyl) chromium and hydrazine, to form materials with low
      coordinate Cr hydride centers as the principal H(2) binding sites, thus
      exploiting the fact that metal hydrides form stronger Kubas interactions than the
      corresponding metal alkyls. This led to up to a 6-fold increase in storage
      capacity at room temperature. The material with the highest capacity has an
      excess reversible storage of 3.23 wt % at 298 K and 170 bar without saturation,
      corresponding to 40.8 kg H(2)/m(3), comparable to the 2015 DOE system goal for
      volumetric density (40 kg/m(3)) at a safe operating pressure. These materials
      possess linear isotherms and enthalpies that rise on coverage, retain up to 100%
      of their adsorption capacities on warming from 77 to 298 K, and have no kinetic
      barrier to adsorption or desorption. In a practical system, these materials would
      use pressure instead of temperature as a toggle and can thus be used in
      compressed gas tanks, currently employed in the majority of hydrogen test
      vehicles, to dramatically increase the amount of hydrogen stored, and therefore
      range of any vehicle.

PMID- 21863870
TI  - Interaction of thioflavin T with amyloid fibrils: stoichiometry and affinity of
      dye binding, absorption spectra of bound dye.
AB  - The fluorescence of the benzothiazole dye thioflavin T (ThT) is a well-known test
      for amyloid fibril formation. It has now become evident that ThT can also be used
      for structural investigations of amyloid fibrils and even for the treatment of
      amyloid diseases. In this case, one of the most urgent problems is an accurate
      determination of ThT-amyloid fibril binding parameters: the number of binding
      modes, stoichiometry, and binding constant for each mode. To obtain information
      concerning the ThT-amyloid fibril binding parameters, we propose to use
      absorption spectrophotometry of solutions prepared by equilibrium microdialysis.
      This approach is inherently designed for the determination of dye-receptor
      binding parameters. However, it has been very rarely used in the study of dye
      protein interactions and has never been used to study the binding parameters of
      ThT or its analogues to amyloid fibrils. We showed that, when done in corpore,
      this approach enables the determination of not only binding parameters but also
      the absorption spectrum and molar extinction coefficient of ThT bound to sites of
      different binding modes. The proposed approach was used for the examination of
      lysozyme amyloid fibrils. Two binding modes were found for the ThT-lysozyme
      amyloid fibril interaction. These binding modes have significantly different
      binding constants (K(b1) = 7.5 * 10(6) M(-1), K(b2) = 5.6 * 10(4) M(-1)) and a
      different number of dye binding sites on the amyloid fibrils per protein molecule
      (n(1) = 0.11, n(2) = 0.24). The absorption spectra of ThT bound to sites of
      different modes differ from each other (epsilon(b1,max) = 5.1 * 10(4) M(-1) cm(
      1), epsilon(b2,max) = 6.7 * 10(4) M(-1)cm(-1), lambda(max) = 449 nm) and
      significantly differ from that of free ThT in aqueous solution (epsilon(max) =
      3.2 * 10(4) M(-1)cm(-1), lambda(max) = 412 nm).

PMID- 21863871
TI  - Inhibitory effect of mimosine on polyphenoloxidase from cephalothoraxes of
      Pacific white shrimp (Litopenaeus vannamei).
AB  - The inhibitory effect of mimosine on polyphenoloxidase (PPO) from the
      cephalothorax of Pacific white shrimp (Litopenaeus vannamei) was studied.
      Mimosine showed inhibitory activity toward PPO from white shrimp with an apparent
      molecular weight of 210 kDa as evidenced by the decrease in the activity staining
      band, as compared to the control. An inhibition kinetic study revealed that
      mimosine exhibited the mixed type reversible inhibition on PPO from white shrimp
      with a Ki value of 3.7 mM. Mimosine showed copper (Cu2+) reduction and chelating
      capacity in a dose dependent manner. Mimosine could react with the intermediate
      browning product, thereby rendering lower red-brown color formation. Therefore,
      mimosine could inhibit PPO by different modes of inhibition and could be used to
      prevent melanosis formation in Pacific white shrimp.

PMID- 21863872
TI  - Varietal differences among the phenolic profiles and antioxidant activities of
      seven table grape cultivars grown in the south of Italy based on chemometrics.
AB  - Seven table grape cultivars grown in Apulia region were considered: Italia,
      Baresana, Pizzutello, Red Globe, Michele Palieri, Crimson Seedless, and Thompson
      Seedless. Seeds, skins and pulps were extracted and analyzed for their phenolic
      profiles and antioxidant activities. The hierarchy in the phenolic contents was
      seeds, skins, and pulps. These results indicate that the intake of the whole
      berries (seeds included) must be strongly recommended. The highest phenolic
      contents were detected on Italia and Michele Palieri cv., respectively within the
      white and the red/black table grapes. Seeds gave a high contribution to the berry
      antioxidant activity, as they had higher phenolic content than skins and
      contained high quantities of proanthocyanidines, but the strongest antioxidant
      activity was shown by the pulp juices due to their content in hydroxycinnamyl
      acids. The principal component analysis applied to the phenolic composition and
      antioxidant activity of skins, pulps, and seeds allowed a good separation of
      Italia and Michele Palieri cultivars. According to the cluster analysis,
      cultivars were grouped into two clusters, one including Michele Palieri and the
      other one including Italia, Baresana, Pizzutello, and Thompson Seedless.

PMID- 21863873
TI  - Phosphonate-anchored monolayers for antibody binding to magnetic nanoparticles.
AB  - Targeted delivery of magnetic iron oxide nanoparticles (IONPs) to a specific
      tissue can be achieved by conjugation with particular biological ligands on an
      appropriately functionalized IONP surface. To take best advantage of the unique
      magnetic properties of IONPs and to maximize their blood half-life, thin,
      strongly bonded, functionalized coatings are required. The work reported herein
      demonstrates the successful application of phosphonate-anchored self-assembled
      monolayers (SAMs) as ultrathin coatings for such particles. It also describes a
      new chemical approach to the anchoring of antibodies on the surface of SAM-coated
      IONPs (using nucleophilic aromatic substitution). This anchoring strategy results
      in stable, nonhydrolyzable, covalent attachment and allows the reactivity of the
      particles toward antibody binding to be activated in situ, such that prior to the
      activation the modified surface is stable for long-term storage. While the SAMs
      do not have the well-packed crystallinity of other such monolayers, their
      structure was studied using smooth model substrates based on an iron oxide layer
      on a double-side polished silicon wafer. In this way, atomic force microscopy,
      ellipsometry, and contact angle goniometry (tools that could not be applied to
      the nanoparticles' surfaces) could contribute to the determination of their
      monomolecular thickness and uniformity. Finally, the successful conjugation of
      IgG antibodies to the SAM-coated IONPs such that the antibodies retain their
      biological activity is verified by their complexation to a secondary fluorescent
      antibody.

PMID- 21863874
TI  - A bidirectional approach to the synthesis of polypropionates: synthesis of C1-C13
      fragment of zincophorin and related isomers.
AB  - The structure-activity study of a bioactive natural product containing
      polypropionate subunits requires that its stereoisomers also be evaluated.
      Therefore, a general approach to synthesize these motifs is necessary. We
      describe herein the synthesis of the C1-C13 polypropionate subunit of zincophorin
      and isomers thereof using a two-reaction sequence: an aldol reaction using a
      mixture of tetrasubstituted enoxysilanes and a hydrogen-transfer reaction, both
      under Lewis acid control. Selection of the appropriate Lewis acid dictates the
      stereochemical outcome of these reactions. From a tactical standpoint, this study
      shows how a polypropionate sequence can be read and constructed in two
      directions, either the east-west or the west-east approaches. The choice of the
      optimal route is influenced by the number of complexation sites that can
      interfere in the aldol step under bidentate Lewis acid control.

PMID- 21863875
TI  - A formal synthesis of (-)-cyanolide A featuring a stereoselective Mukaiyama aldol
      reaction and oxocarbenium reduction.
AB  - The formal synthesis of the marine natural product (-)-cyanolide A is presented.
      The synthetic strategy is centered on two acyclic diastereoselective reactions
      and a single cyclic reaction with modest to excellent dr based on an initial
      stereocenter. Most notable is a highly stereoselective oxocarbenium reduction
      based on a "mismatched" reactive conformer to afford the beta-C-glycoside subunit
      leading to an efficient synthesis of the diolide aglycon in 12 overall steps.

PMID- 21863876
TI  - Genotype and environment effects on the contents of vitamins B1, B2, B3, and B6
      in wheat grain.
AB  - The total contents of thiamine (vitamin B1), riboflavin (B2), and pyridoxine (B6)
      and the bioavailable forms of niacin (B3) were determined on wholemeal flours of
      24 winter wheat varieties grown on four sites (United Kingdom, Poland, France,
      and Hungary) in 2007 and of two spring varieties grown on the same sites with the
      exception of Poland. The contents of vitamins B1 (5.53-13.55 MUg/g dw), B2 (0.77
      1.40 MUg/g dw), and B6 (1.27-2.97 MUg/g dw) were within the ranges reported
      previously, while the content of bioavailable vitamin B3 (0.16-1.74 MUg/g dw) was
      about 10-15% of the total contents of vitamin B3 reported in previous studies.
      Strong correlations were observed between the contents of vitamins B1, B3, and
      B6, and partitioning of the variance in the contents of these three B vitamins
      showed that between 48 and 70% was accounted for by the environment. By contrast,
      the content of vitamin B2 was not correlated with the contents of other B
      vitamins, and 73% of the variance was ascribed to the error term, which suggests
      that this trait may be influenced by genotype * environment interactions. Whereas
      the contents of vitamins B1, B3, and B6 were correlated positively with the mean
      temperature from heading to harvest (r > 0.8), the content of vitamin B2 was
      positively correlated with precipitation during the 3 months prior to heading.
      These results are discussed in relation to the development of new wheat varieties
      with enhanced health benefits.

PMID- 21863877
TI  - Tribute to David W. Pratt.

PMID- 21863878
TI  - Scientific autobiography of David W. Pratt.

PMID- 21863882
TI  - Asymmetric synthesis of cyclohexene nucleoside analogues.
AB  - The asymmetric synthesis of novel cyclohexene nucleoside analogues 12 and 15 is
      described. An enantiospecific Diels-Alder reaction between (E,E)-diene 2 and (+)
      5-(d-mentyloxy)-2(5H)-furanone 3 provided the cycloadduct isomer 4. Three
      additional steps yielded amine 8 allowing the constructions of the thymine and
      adenine moieties to afford intermediates 11 and 14, respectively. Amination or
      cyclization and removal of the protecting groups occurred in one step in the
      presence of ammonia, giving the target six-membered ring nucleosides.

PMID- 21863883
TI  - Trivalent PEGylated platform for the conjugation of bioactive compounds.
AB  - PEGylated multivalent structures are a new class of platform for biological
      applications due to their biocompatibility properties. Here, we present the
      synthesis of a trivalent structure 1 based on poly(ethylene glycol) units (PEG)
      as potential synthetic multifunctional carrier molecule. To evaluate whether this
      PEGylated platform could be useful for the conjugation of bioactive compounds, a
      well-known lipopolysaccharide (LPS) inhibitor 2, developed in our laboratory, was
      selected to be conjugated to 1. The LPS-neutralizing activity of the resulted
      conjugates and precursors was established using the chromogenic Limulus amebocyte
      lysate (LAL) assay. The trivalent structure 1 did not show LPS-binding activity,
      nonconjugate LPS inhibitor 2 showed high LPS-neutralizing activity, and the
      trivalent conjugate 4 displayed increased LPS-neutralizing activity and a reduced
      toxicity profile. These results prove the efficacy of this trivalent platform as
      a multivalent ligand scaffold for biological applications.

PMID- 21863884
TI  - Differential solute gas response in ionic-liquid-based QCM arrays: elucidating
      design factors responsible for discriminative explosive gas sensing.
AB  - An eight-sensor array coupling a chemoselective room-temperature ionic liquid
      (RTIL) with quartz crystal microbalance (QCM) transduction is presented in this
      work in order to demonstrate the power of this approach in differentiating
      closely related analytes in sensory devices. The underlying mechanism behind the
      specific sensory response was explored by (i) studying mass loading and
      viscoelasticity effects of the sensing layers, predominantly through variation in
      damping impedance, the combination of which determines the sensitivity; (ii)
      creation of a solvation model based on Abraham's solvation descriptors which
      reveals the fact that polarizability and lipophilicity are the main factors
      influencing the dissolution of gas analytes into the RTILs; and (iii)
      determination of enthalpy and entropy values for the studied interactions and
      comparison via a simulation model, which is also effective for pattern
      discrimination, in order to establish a foundation for the analytical scientist
      as well as inspiration for synthetic pathways and innovative research into next
      generation sensory approaches. The reported sensors displayed an excellent
      sensitivity with detection limit of <0.2%, fast response and recovery, and a
      workable temperature range of 27-55  degrees C and even higher. Linear
      discriminant analysis (LDA) showed a discrimination accuracy of 86-92% for
      nitromethane and 1-ethyl-2-nitrobenzene, 71% for different mixtures of
      nitromethane, and 100% for these analytes when thermodynamic parameters were used
      as input data. We envisage applications to detecting other nitroaromatics and
      security-related gas targets, and high-temperature or real-time situations where
      manual access is restricted, opening up new horizons in chemical sensing.

PMID- 21863886
TI  - Ti-doped LiAlH4 for hydrogen storage: synthesis, catalyst loading and cycling
      performance.
AB  - The direct synthesis of LiAlH(4) from commercially available LiH and Al powders
      in the presence of TiCl(3) and Me(2)O has been achieved for the first time. The
      effects of TiCl(3) loadings (Ti/Al = 0, 0.01, 0.05, 0.2, 0.5, 1.0 and 2.0%) and
      various other additives (TiCl(3)/Al(2)O(3), metallic Ti, Nb(2)O(5), and NbCl(5))
      on the formation and stability of LiAlH(4) have been systematically investigated.
      The yield of LiAlH(4) initially increases, and then decreases, with increasing
      TiCl(3) loadings. LiH + Al -> LiAlH(4) yields above 95% were obtained when the
      molar ratios of Ti/Al were 0.05 and 0.2%. In the presence of a very tiny amount
      of TiCl(3) (Ti/Al = 0.01%), LiAlH(4) is still generated, but the yield is lower.
      In the complete absence of TiCl(3), LiAlH(4) does not form. Addition of metallic
      Ti, Nb(2)O(5), and NbCl(5) to commercial LiH and Al does not result in the
      formation of LiAlH(4). Preliminary tests show that TiCl(3)-doped LiAlH(4) can be
      cycled, making it a suitable candidate for hydrogen storage.

PMID- 21863885
TI  - Novel anticancer polymeric conjugates of activated nucleoside analogues.
AB  - Inherent or therapy-induced drug resistance is a major clinical setback in cancer
      treatment. The extensive usage of cytotoxic nucleobases and nucleoside analogues
      in chemotherapy also results in the development of specific mechanisms of drug
      resistance, such as nucleoside transport or activation deficiencies. These drugs
      are prodrugs; and being converted into the active mono-, di-, and triphosphates
      inside cancer cells following administration, they affect nucleic acid synthesis,
      nucleotide metabolism, or sensitivity to apoptosis. Previously, we actively
      promoted the idea that the nanodelivery of active nucleotide species, e.g., 5'
      triphosphates of nucleoside analogues, can enhance drug efficacy and reduce
      nonspecific toxicity. In this study, we report the development of a novel type of
      drug nanoformulations, polymeric conjugates of nucleoside analogues, which are
      capable of the efficient transport and sustained release of phosphorylated drugs.
      These drug conjugates have been synthesized, starting from cholesterol-modified
      mucoadhesive polyvinyl alcohol or biodegradable dextrin, by covalent attachment
      of nucleoside analogues through a tetraphosphate linker. Association of
      cholesterol moieties in aqueous media resulted in intramolecular polymer folding
      and the formation of small nanogel particles containing 0.5 mmol/g of a 5'
      phosphorylated nucleoside analogue, e.g., 5-fluoro-2'-deoxyuridine (floxuridine,
      FdU), an active metabolite of anticancer drug 5-fluorouracyl (5-FU). The
      polymeric conjugates demonstrated rapid enzymatic release of floxuridine 5'
      phosphate and much slower drug release under hydrolytic conditions (pH 1.0-7.4).
      Among the panel of cancer cell lines, all studied polymeric FdU-conjugates
      demonstrated an up to 50* increased cytotoxicity in human prostate cancer PC-3,
      breast cancer MCF-7, and MDA-MB-231 cells, and more than 100* higher efficacy
      against cytarabine-resistant human T-lymphoma (CEM/araC/8) and gemcitabine
      resistant follicular lymphoma (RL7/G) cells as compared to free drugs. In the
      initial in vivo screening, both PC-3 and RL7/G subcutaneous tumor xenograft
      models showed enhanced sensitivity to sustained drug release from polymeric FdU
      conjugate after peritumoral injections and significant tumor growth inhibition.
      All these data demonstrate a remarkable clinical potential of novel polymeric
      conjugates of phosphorylated nucleoside analogues, especially as new therapeutic
      agents against drug-resistant tumors.

PMID- 21863887
TI  - Phenol acidity and ease of oxidation in isoflavonoid/beta-carotene antioxidant
      synergism.
AB  - Regeneration of beta-carotene from the beta-carotene radical cation by the 4'
      propylpuerarin anion (second-order rate constant=1.5*10(9) L mol(-1) s(-1) in
      methanol/chloroform=1:9 (v/v) solution at 25  degrees C as determined by laser
      flash photolysis) was found to be marginally slower than regeneration by the 7
      propylpuerarin anion (2.3*10(9) L mol(-1) s(-1)), in agreement with the 7
      propylpuerarin anion being more reducing (E'=0.56 V vs NHE) than the 4'
      propylpuerarin anion (E'=1.01 V vs NHE). The potentials were calculated from E
      degrees =1.12 and 1.44 V (vs NHE) as determined by cyclic voltametry in aqueous
      solution and pKa=9.51 and 7.23 obtained previously for 7-propylpuerarin and 4'
      propylpuerarin, respectively. The less reducing but more acidic 4'-propylpuerarin
      showed less antioxidant activity in liposome of pH 7.4, but more significant
      antioxidant synergism with beta-carotene than the more reducing but less acidic 7
      propylpuerarin for oxidation initiated in the liposome lipid phase. Electrostatic
      effects are concluded to be important in the regeneration of beta-carotene from
      the radical cation in the water/lipid interface because approximately 50% of 4'
      propylpuerarin is present as the anion, whereas only 0.5% of 7-propylpuerarin is
      present as the anion. In contrast, penetration of the undissociated phenolic
      group into the lipid phase, more significant for 7-propylpuerarin than for 4'
      propylpuerarin according to the calculated water/lipid partition coefficients,
      becomes important for the chain-breaking action in lipid oxidation of the
      puerarin derivatives as models for (iso)flavonoids and their glycosides.

PMID- 21863888
TI  - Efficient conversion of a nonselective norepinephrin reuptake inhibitor into a
      dual muscarinic antagonist-beta2-agonist for the treatment of chronic obstructive
      pulmonary disease.
AB  - Following interrogation of a wide-ligand profile database, a nonselective
      norepinephrin reuptake inhibitor was converted into a novel muscarinic antagonist
      using two medicinal chemistry transformations (M3/NRI selectivity of >1000).
      Conjugation to a beta(2) agonist motif furnished a molecule with balanced dual
      pharmacology, as demonstrated in a guinea pig trachea tissue model of
      bronchoconstriction. This approach provides new starting points for the treatment
      of chronic obstructive pulmonary disease and illustrates the potential for
      building selectivity into GPCR modulators that possess intrinsic promiscuity or
      reverse selectivity.

PMID- 21863889
TI  - 4-benzimidazolyl-3-phenylbutanoic acids as novel PIF-pocket-targeting allosteric
      inhibitors of protein kinase PKCzeta.
AB  - Protein kinase inhibitors with an allosteric mode of action are expected to
      reach, in many cases, higher selectivity for the target enzyme than ATP
      competitive compounds. Therefore, basic research is aiming at identifying and
      establishing novel sites on the catalytic domain of protein kinases which might
      be targeted by allosteric inhibitors. We previously published the first structure
      activity relationships (SARs) for allosteric activators of protein kinase PDK1.
      Here, we present the design, synthesis, and SAR data on a series of novel
      compounds, 4-benzimidazolyl-3-phenylbutanoic acids, that inhibit the atypical
      protein kinace C (PKC) zeta via binding to the PIF-pocket. Key positions were
      identified in the compounds that can be modified to increase potency and
      selectivity. Some congeners showed a high selectivity toward PKCzeta, lacking
      inhibition of the most closely related isoform, PKCiota, and of further AGC
      kinases. Furthermore, evidence is provided that these compounds are also active
      toward cellular PKCzeta without loss of potency compared to the cell-free assay.

PMID- 21863891
TI  - Oxime linkage: a robust tool for the design of pH-sensitive polymeric drug
      carriers.
AB  - Oxime bonds dispersed in the backbones of the synthetic polymers, while young in
      the current spectrum of the biomedical application, are rapidly extending into
      their own niche. In the present work, oxime linkages were confirmed to be a
      robust tool for the design of pH-sensitive polymeric drug delivery systems. The
      triblock copolymer (PEG-OPCL-PEG) consisting of hydrophilic poly(ethylene glycol)
      (PEG) and hydrophobic oxime-tethered polycaprolactone (OPCL) was successfully
      prepared by aminooxy terminals of OPCL ligating with aldehyde-terminated PEG (PEG
      CHO). Owing to its amphiphilic architecture, PEG-OPCL-PEG self-assembled into the
      micelles in aqueous media, validated by the measurement of critical micelle
      concentration (CMC). The MTT assay showed that PEG-OPCL-PEG exhibited low
      cytotoxicity against NIH/3T3 normal cells. Doxorubicin (DOX) as a model drug was
      encapsulated into the PEG-OPCL-PEG micelles. Drug release study revealed that the
      DOX release from micelles was significantly accelerated at mildly acid pH of 5.0
      compared to physiological pH of 7.4, suggesting the pH-responsive feature of the
      drug delivery systems with oxime linkages. Flow cytometry and confocal laser
      scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles
      were easily internalized by living cells. MTT assay against HeLa cancer cells
      showed DOX-loaded PEG-OPCL-PEG micelles had a high anticancer efficacy. All of
      these results demonstrate that these polymeric micelles self-assembled from oxime
      tethered block copolymers are promising carriers for the pH-triggered
      intracellular delivery of hydrophobic anticancer drugs.

PMID- 21863890
TI  - Coiled coil peptides as universal linkers for the attachment of recombinant
      proteins to polymer therapeutics.
AB  - We have designed, synthesized, and characterized peptides containing four repeats
      of the sequences VAALEKE (peptide E) or VAALKEK (peptide K). While the peptides
      alone adopt in aqueous solutions a random coil conformation, their equimolar
      mixture forms heterodimeric coiled coils as confirmed by CD spectroscopy. 5
      Azidopentanoic acid was connected to the N-terminus of peptide E via a short
      poly(ethylene glycol) spacer. The terminal azide group enabled conjugation of the
      peptide with a synthetic drug carrier based on the N-(2
      hydroxypropyl)methacrylamide copolymer containing propargyl groups using "click"
      chemistry. When incorporated into the polymer drug carrier, peptide E formed a
      stable noncovalent complex with peptide K belonging to a recombinant single-chain
      fragment (scFv) of the M75 antibody. The complex thereby mediates a noncovalent
      linkage between the polymer drug carrier and the protein. The recombinant scFv
      antibody fragment was selected as a targeting ligand against carbonic anhydrase
      IX-a marker overexpressed by tumor cells of various human carcinomas. The antigen
      binding affinity of the polymer-scFv complex was confirmed by ELISA. This
      approach offers a well-defined, specific, and nondestructive universal method for
      the preparation of protein (antibody)-targeted polymer drug and gene carriers
      designed for cell-specific delivery.

PMID- 21863892
TI  - Systems biology approach predicts antibody signature associated with Brucella
      melitensis infection in humans.
AB  - A complete understanding of the factors that determine selection of antigens
      recognized by the humoral immune response following infectious agent challenge is
      lacking. Here we illustrate a systems biology approach to identify the antibody
      signature associated with Brucella melitensis (Bm) infection in humans and
      predict proteomic features of serodiagnostic antigens. By taking advantage of a
      full proteome microarray expressing previously cloned 1406 and newly cloned 1640
      Bm genes, we were able to identify 122 immunodominant antigens and 33
      serodiagnostic antigens. The reactive antigens were then classified according to
      annotated functional features (COGs), computationally predicted features (e.g.,
      subcellular localization, physical properties), and protein expression estimated
      by mass spectrometry (MS). Enrichment analyses indicated that membrane
      association and secretion were significant enriching features of the reactive
      antigens, as were proteins predicted to have a signal peptide, a single
      transmembrane domain, and outer membrane or periplasmic location. These features
      accounted for 67% of the serodiagnostic antigens. An overlay of the seroreactive
      antigen set with proteomic data sets generated by MS identified an additional
      24%, suggesting that protein expression in bacteria is an additional determinant
      in the induction of Brucella-specific antibodies. This analysis indicates that
      one-third of the proteome contains enriching features that account for 91% of the
      antigens recognized, and after B. melitensis infection the immune system develops
      significant antibody titers against 10% of the proteins with these enriching
      features. This systems biology approach provides an empirical basis for
      understanding the breadth and specificity of the immune response to B. melitensis
      and a new framework for comparing the humoral responses against other
      microorganisms.

PMID- 21863893
TI  - Investigation of flavonoids bearing different substituents on ring C and their
      cu2+ complex binding with bovine serum albumin: structure-affinity relationship
      aspects.
AB  - The effects of 1:1 flavonoid-Cu(2+) complexes of four flavonoids with different C
      ring substituents, quercetin (QU), luteolin (LU), taxifolin (TA), and (+)
      catechin (CA), on bovine serum albumin (BSA) were investigated and compared with
      corresponding free flavonoids by spectroscopic analysis in an attempt to
      characterize the chemical association taking place. The results indicated that
      all of the quenching mechanisms were based on static quenching combined with
      nonradiative energy transfer. Cu(2+) chelation changed the binding constants for
      BSA depending on the structures of flavonoids and the detected concentrations.
      The reduced hydroxyl groups, increased steric hindrance, and hydrophilicity of
      Cu(2+) chelation may be the main reasons for the reduced binding constants,
      whereas the formation of stable flavonoid-Cu(2+) complexes and synergistic action
      could increase the binding constants. The changed trends of critical energy
      transfer distance (R(0)) for Cu(2+) chelation were contrary to those of binding
      constants.

PMID- 21863894
TI  - Directed intermixing in multicomponent self-assembling biomaterials.
AB  - The noncovalent coassembly of multiple different peptides can be a useful route
      for producing multifunctional biomaterials. However, to date, such materials have
      almost exclusively been investigated as homogeneous self-assemblies, having
      functional components uniformly distributed throughout their supramolecular
      structures. Here we illustrate control over the intermixing of multiple different
      self-assembling peptides, in turn providing a simple but powerful means for
      modulating these materials' mechanical and biological properties. In beta-sheet
      fibrillizing hydrogels, significant increases in stiffening could be achieved
      using heterobifunctional cross-linkers by sequestering peptides bearing different
      reactive groups into distinct populations of fibrils, thus favoring interfibril
      cross-linking. Further, by specifying the intermixing of RGD-bearing peptides in
      2-D and 3-D self-assemblies, the growth of HUVECs and NIH 3T3 cells could be
      significantly modulated. This approach may be immediately applicable toward a
      wide variety of self-assembling systems that form stable supramolecular
      structures.

PMID- 21863896
TI  - Catalytic asymmetric alpha-alkylation of ketones and aldehydes with N-benzylic
      sulfonamides through carbon-nitrogen bond cleavage.
AB  - A range of ketones and aldehydes smoothly undergo asymmetric S(N)1 alpha
      alkylation with N-benzylic sulfonamides in the presence of 10 mol % of a chiral
      imidazolidinone and trifluoroacetic acid to give the corresponding products in
      good to excellent yields and with good enantioselectivity. This chemistry has
      been successfully extended to the asymmetric desymmetrization of 4-substituted
      cyclohexanones, which exhibits greater than 99:1 diastereoselectivity and good
      enantioselectivity.

PMID- 21863895
TI  - Thermodynamics of nucleic acid "shape readout" by an aminosugar.
AB  - Recognition of nucleic acids is important for our understanding of nucleic acid
      structure as well as for our understanding of nucleic acid-protein interactions.
      In addition to the direct readout mechanisms of nucleic acids such as H-bonding,
      shape recognition of nucleic acids is being increasingly recognized as playing an
      equally important role in DNA recognition. Competition dialysis, UV, flourescent
      intercalator displacement (FID), computational docking, and calorimetry studies
      were conducted to study the interaction of neomycin with a variety of nucleic
      acid conformations (shapes). At pH 5.5, the results suggest the following. (1)
      Neomycin binds three RNA structures [16S A site rRNA, poly(rA).poly(rA), and
      poly(rA).poly(rU)] with high affinities (K(a) ~ 10(7) M(-1)). (2) The binding of
      neomycin to A-form GC-rich oligomer d(A(2)G(15)C(15)T(2))(2) has an affinity
      comparable to those of RNA structures. (3) The binding of neomycin to DNA.RNA
      hybrids shows a 3-fold variance that can be attributed to their structural
      differences [for poly(dA).poly(rU), K(a) = 9.4 * 10(6) M(-1), and for
      poly(rA).poly(dT), K(a) = 3.1 * 10(6) M(-1)]. (4) The interaction of neomycin
      with DNA triplex poly(dA).2poly(dT) yields a binding affinity (K(a)) of 2.4 *
      10(5) M(-1). (5) Poly(dA-dT)(2) shows the lowest association constant for all
      nucleic acids studied (K(a) < 10(5)). (6) Neomycin binds to G-quadruplexes with
      K(a) values of ~10(4)-10(5) M(-1). (7) Computational studies show that the
      decrease in major groove width in the B to A transition correlates with
      increasing neomycin affinity. Neomycin's affinity for various nucleic acid
      structures can be ranked as follows: RNAs and GC-rich d(A(2)G(15)C(15)T(2))(2)
      structures > poly(dA).poly(rU) > poly(rA).poly(dT) > T.A-T triplex, G-quadruplex,
      B-form AT-rich, or GC-rich DNA sequences. The results illustrate the first
      example of a small molecule-based "shape readout" of different nucleic acid
      conformations.

PMID- 21863897
TI  - N-nitrosamines formation from secondary amines by nitrogen fixation on the
      surface of activated carbon.
AB  - Our previous study demonstrated that many commercial activated carbon (AC)
      particles may catalyze transformation of secondary amines to yield trace levels
      of N-nitrosamines under ambient aerobic conditions. Because of the widespread
      usage of AC materials in numerous analytical and environmental applications, it
      is imperative to understand the reaction mechanism responsible for formation of
      nitrosamine on the surface of ACs to minimize their occurrence in water treatment
      systems and during analytical methods employing ACs. The study results show that
      the AC-catalyzed nitrosamine formation requires both atmospheric oxygen and
      nitrogen. AC's surface reactive sites react with molecular oxygen to form
      reactive oxygen species (ROS), which facilitate fixation of molecular nitrogen on
      the carbon surfaces to generate reactive nitrogen species (RNS) likely nitrous
      oxide and hydroxylamine that can react with adsorbed amines to form nitrosamines.
      AC's properties play a crucial role as more nitrosamine formation is associated
      with carbon surfaces with higher surface area, more surface defects, reduced
      surface properties, higher O(2) uptake capacity, and higher carbonyl group
      content. This study is a first of its kind on the nitrosamine formation mechanism
      involving nitrogen fixation on AC surfaces, and the information will be useful
      for minimization of nitrosamines in AC-based processes.

PMID- 21863898
TI  - Dewetting transitions in the self-assembly of two amyloidogenic beta-sheets and
      the importance of matching surfaces.
AB  - We use molecular dynamics simulations to investigate the water-mediated self
      assembly of two amyloidogenic beta-sheets of hIAPP(22-27) peptides (NFGAIL). The
      initial configurations of beta-sheet pairs are packed with two different modes,
      forming a tube-like nanoscale channel and a slab-like 2-D confinement,
      respectively. For both packing modes, we observe strong water drying transitions
      occurring in the intersheet region with high occurrence possibilities, suggesting
      that the "dewetting transition"-induced collapse may play an important role in
      promoting the amyloid fibrils formation. However, contrary to general dewetting
      theory prediction, the slab-like confinement (2-D) shows stronger dewetting
      phenomenon than the tube-like channel (1-D). This unexpected observation is
      attributed to the different surface roughness caused by different packing modes.
      Furthermore, we demonstrated the profound influence of internal surface topology
      of beta-sheet pairs on the dewetting phenomenon through an in silico mutagenesis
      study. The present study highlights the important role of packing modes (i.e.,
      surface roughness) in the assembly process of beta-sheets, which improves our
      understanding toward the molecular mechanism of the amyloid fibrils formation. In
      addition, our study also suggests a potential route to regulate controllably the
      self-assembly process of beta-sheets through mutations, which may have future
      applications in nanotechnology and biotechnology.

PMID- 21863899
TI  - Synthesis of poly-L-glutamic acid grafted silica nanoparticles and their assembly
      into macroporous structures.
AB  - Polypeptide-coated silica nanoparticles represent an interesting class of organic
      inorganic hybrids since the ordered secondary structure of the polypeptide grafts
      imparts functional properties to these nanoparticles. The synthesis of a poly-l
      glutamic acid (PLGA) silica nanoparticle hybrid by employing N-carboxyanhydride
      (NCA) polymerization to synthesize the polypeptide chains and Cu catalyzed azide
      alkyne cycloaddition reaction to graft these chains onto the silica surface is
      reported. This methodology enables the synthesis of well-defined polypeptide
      chains that are attached onto the silica surface at high surface densities. The
      PLGA-silica conjugate particles are well dispersed in water, and have been
      thoroughly characterized using multinuclear ((13)C, (29)Si) solid state NMR,
      thermogravimetric analysis, Fourier transform infrared, dynamic light scattering,
      and transmission electron microscopy. The pH-dependent reversible aggregation of
      the PLGA-silica particles, driven by the change in PLGA structure, has also been
      studied. Preliminary results on the use of aqueous dispersions of silica-PLGA for
      the preparation of three-dimensional macroporous structures with oriented pores
      by ice templating methodology are also demonstrated. These macroporous materials,
      comprising a biocompatible polymer shell covalently attached to rigid inorganic
      cores, adopts an interesting lamellar structure with fishbone-type architecture.

PMID- 21863900
TI  - Two-electron reduced density matrix as the basic variable in many-electron
      quantum chemistry and physics.

PMID- 21863901
TI  - Experimental method to measure the effect of charge on bimolecular collision
      rates in electrolyte solutions.
AB  - A stable, monoprotic nitroxide spin probe is utilized as a model to study
      molecular collisions in aqueous electrolyte solutions. The rate constants of
      bimolecular collisions, K(col) for 2,2,5,5-tetramethylpyrrolidin-1-oxyl-3
      carboxylic acid (CP) when it is uncharged (at low pH) and K(col)- when it is
      charged (CP-; at high pH), are measured as functions of temperature and ionic
      strength. The ratio f* = K(col)-/K(col) is a direct measure of the effect of
      charge on the collision rate. Neglecting the small differences in size and
      diffusion coefficients of CP and CP-, f* is the fractional change in collision
      rate due to Coulomb repulsion which was treated theoretically in Debye's classic
      paper [Trans. Electr. Chem. Soc. 1942, 82, 265]. K(col) and K(col)- are
      determined from EPR spectral changes due to spin-spin interactions which are
      dominated by Heisenberg spin exchange under the conditions of these experiments.
      Values of f* vary linearly with values of kappa . d in the range 0.4 < kappa . d
      < 1.8, where kappa and d are the inverse Debye screening length and the distance
      at closest approach, respectively. Values of d obtained in two independent ways,
      (1) from rotational correlation times measured by EPR and (2) by insisting that
      the experimental results be consistent with the Debye theory at infinite
      dilution, yield similar results. As the ionic strength is increased (kappa
      increased), the screening effect reduces the effect of the Coulomb barrier more
      slowly than predicted by the Debye theory. While values of K(col) and K(col)-
      vary substantially with T, approximately following the Stokes-Einstein
      Smoluchowski equation, values of f* depend only slightly on temperature at a
      given value of kappa . d, as is predicted by Debye's theory.

PMID- 21863902
TI  - Catalytic enantioselective desymmetrization of meso-diamines: a dual small
      molecule catalysis approach.
AB  - The desymmetrization of meso-diamines was accomplished via enantioselective
      monobenzoylation facilitated by the cooperative action of two small-molecule
      catalysts. A chiral acyl-transfer reagent is formed in situ through the interplay
      of benzoic anhydride, 4-(dimethylamino)pyridine as a nucleophilic catalyst, and a
      chiral amide-thiourea cocatalyst.

PMID- 21863903
TI  - Sonofragmentation of molecular crystals.
AB  - Possible mechanisms for the breakage of molecular crystals under high-intensity
      ultrasound were investigated using acetylsalicylic acid (aspirin) crystals as a
      model compound for active pharmaceutical ingredients. Surprisingly, kinetics
      experiments ruled out particle-particle collisions as a viable mechanism for
      sonofragmentation. Two other possible mechanisms (particle-horn and particle-wall
      collisions) were dismissed on the basis of decoupling experiments. Direct
      particle-shock wave interactions are therefore indicated as the primary mechanism
      of sonofragmentation of molecular crystals.

PMID- 21863905
TI  - Deconvoluting subensemble chemical reaction kinetics of platinum-sulfur ligand
      exchange detected with single-molecule fluorescence microscopy.
AB  - The subensemble kinetics of a platinum-sulfur covalent chemical reaction at the
      solution/surface interface of a model industrial catalyst support was examined
      using single-molecule fluorescence microscopy (SMFM) and was found to exhibit
      biexponential first-order kinetic behavior. The observed kinetics was a
      convolution of the observation probability and chemical reaction rate. These
      results suggest that deconvolution strategies may be broadly important for
      obtaining accurate chemical reaction kinetics with SMFM.

PMID- 21863904
TI  - Tunable degradation of maleimide-thiol adducts in reducing environments.
AB  - Addition chemistries are widely used in preparing biological conjugates, and in
      particular, maleimide-thiol adducts have been widely employed. Here, we show that
      the resulting succinimide thioether formed by the Michael-type addition of thiols
      to N-ethylmaleimide (NEM), generally accepted as stable, undergoes retro and
      exchange reactions in the presence of other thiol compounds at physiological pH
      and temperature, offering a novel strategy for controlled release. Model studies
      ((1)H NMR, HPLC) of NEM conjugated to 4-mercaptophenylacetic acid (MPA), N
      acetylcysteine, or 3-mercaptopropionic acid (MP) incubated with glutathione
      showed half-lives of conversion from 20 to 80 h, with extents of conversion from
      20% to 90% for MPA and N-acetylcysteine conjugates. After ring-opening, the
      resultant succinimide thioether did not show retro and exchange reactions. The
      kinetics of the retro reactions and extent of exchange can be modulated by the
      Michael donor's reactivity; therefore, the degradation of maleimide-thiol adducts
      could be tuned for controlled release of drugs or degradation of materials at
      time scales different than those currently possible via disulfide-mediated
      release. Such approaches may find a new niche for controlled release in reducing
      environments relevant in chemotherapy and subcellular trafficking.

PMID- 21863906
TI  - Primary cutaneous small- to medium-sized CD4+ pleomorphic T-cell lymphoma: a
      retrospective case series and review of the provisional cutaneous lymphoma
      category.
AB  - BACKGROUND AND OBJECTIVE: Primary cutaneous small- to medium-sized CD4+
      pleomorphic T-cell lymphoma (PCSM-TCL) is a rare and provisional subcategory of
      cutaneous T-cell lymphoma, associated with a favorable prognosis. We present five
      cases of PCSM-TCL and review the literature to address questions surrounding its
      diagnosis and treatment. METHODS: A retrospective review was conducted of 353
      patients with non-mycosis fungoides cutaneous lymphomas evaluated at the M.D.
      Anderson Cancer Center Cutaneous Lymphoma Clinic over 10 years. A retrospective
      search of the English literature using PubMed was conducted to identify
      additional cases. RESULTS: Only five patients had a diagnosis of PCSM-TCL. Three
      patients had unique multifocal presentations that responded well to topical
      therapy or excision. One patient with localized disease initially treated with
      radiation therapy had an aggressive relapse requiring systemic therapy. One
      patient had an isolated nodule that fully resolved with excision. The review of
      the English literature found 232 additional cases. The presentation of PCSM-TCL
      was heterogeneous and included solitary/localized papules, nodules, plaques, and
      tumors. Multiple differential diagnoses were considered and PCSM-TCL diagnosis
      was based on histopathologic features and clinical correlation. Treatment of
      solitary/localized lesions included excision or radiation therapy. Multifocal
      lesions were uncommon and associated with an aggressive course requiring systemic
      chemotherapy. CONCLUSIONS: The heterogeneous presentation, variable histologic
      overlap with other lymphoproliferative disorders, and uncertain prognosis of PCSM
      TCL creates diagnostic and management dilemmas for clinicians. For treatment, a
      distinction should be made between indolent and aggressive subtypes. Further
      investigation is needed to determine if PCSM-TCL is indeed a distinct lymphoma
      category and, additionally, if aggressive subtypes should remain part of the same
      diagnostic category.

PMID- 21863907
TI  - Government bodies and their influence on the 2009 H1N1 health sector pandemic
      response in remote and isolated First Nation communities of sub-Arctic Ontario,
      Canada.
AB  - INTRODUCTION: First Nation communities were highly impacted by the 2009 H1N1
      influenza pandemic. Multiple government bodies (ie federal, provincial, and First
      Nations) in Canada share responsibility for the health sector pandemic response
      in remote and isolated First Nation communities and this may have resulted in a
      fragmented pandemic response. This study aimed to discover if and how the
      dichotomy (or trichotomy) of involved government bodies led to barriers faced and
      opportunities for improvement during the health sector response to the 2009 H1N1
      pandemic in three remote and isolated sub-arctic First Nation communities of
      northern Ontario, Canada. METHODS: A qualitative community-based participatory
      approach was employed. Semi-directed interviews were conducted with adult key
      informants (n=13) using purposive sampling of participants representing the two
      (or three) government bodies of each study community. Data were manually
      transcribed and coded using deductive and inductive thematic analysis to reveal
      positive aspects, barriers faced, and opportunities for improvement along with
      the similarities and differences regarding the pandemic responses of each
      government body. RESULTS: Primary barriers faced by participants included
      receiving contradicting governmental guidelines and direction from many sources.
      In addition, there was a lack of human resources, information sharing, and
      specific details included in community-level pandemic plans. Recommended areas of
      improvement include developing a complementary communication plan, increasing
      human resources, and updating community-level pandemic plans. CONCLUSIONS:
      Participants reported many issues that may be attributable to the dichotomy (or
      trichotomy) of government bodies responsible for healthcare delivery during a
      pandemic. Increasing formal communication and collaboration between responsible
      government bodies will assist in clarifying roles and responsibilities and
      improve the pandemic response in Canada's remote and isolated First Nation
      communities.

PMID- 21864009
TI  - A psychodynamic formulation masterclass with Nancy McWilliams.
AB  - OBJECTIVE: The aim of this paper was to assess the value of a psychodynamic
      formulation masterclass. METHOD: Formal feedback from the presenters at a
      masterclass at the 2010 RANZCP Congress was obtained and arranged under different
      themes. RESULTS: The importance of counter-transference, reevaluating the case
      and supervision, witnessing the skill of an expert, the sense of containment and
      validation, and the importance of formulation were significant themes that
      emerged. CONCLUSIONS: The results provided evidence both for the importance of
      psychodynamic formulation and for the use of a psychodynamic formulation
      masterclass.

PMID- 21864010
TI  - Clozapine use and outcomes among patients with treatment resistant schizophrenia.
AB  - OBJECTIVE: The phenomenology of patients with schizophrenia is similar world
      wide, regardless of culture. However, the prognosis is variable both
      internationally and within national groups of patients. Furthermore, despite
      advances in pharmacological treatment, a significant proportion of patients with
      schizophrenia continue to show residual symptoms and disabilities due to poor
      response to antipsychotic medication. This study retrospectively assessed
      differences in outcome by gender, ethnicity and age among a group of treatment
      resistant patients with schizophrenia. METHOD: Patients in the catchment (350,000
      people) of a single New Zealand public mental health provider (Waikato) formed
      the study group. Information concerning demographic profiles, Health of the
      Nation Outcome Scales (HoNOS) ratings and details of Clozapine usage were
      extracted from clinical records and the data base. RESULTS: Gender, ethnicity and
      age did not emerge as significantly associated with any of the outcome variables
      except for the 30-40 year olds having more improvement on overactivity/aggression
      ratings than younger or older patients. CONCLUSIONS: Despite these negative
      results in the New Zealand context, there remain many unanswered questions about
      the higher rate of service use by Maori. Replication of this study on a larger
      cohort of patients may be indicated before discarding the idea of potential links
      between ethnicity, treatment choice and outcomes.

PMID- 21864011
TI  - Cognition-focused interventions for older adults: the state of play.
AB  - OBJECTIVE: The aim of this study was to review and discuss the evidence
      supporting the use of cognition-focused interventions to enhance mental function
      and decrease the risk of dementia. METHOD: A non-quantitative review was made of
      existing evidence supporting the use of cognitive stimulation, rehabilitation and
      training in enhancing mental function and decreasing the risk of dementia in
      later life. RESULTS: Despite growing popularity, there is limited evidence from
      randomized trials to support the use of cognition-focused interventions to
      decrease the rate of cognitive decline associated with increasing age or with
      dementia. There is currently no evidence available from randomized trials to
      support the use of cognition-focused interventions to prevent dementia.
      CONCLUSIONS: Sufficiently powered randomized trials of cognition-focused
      interventions designed to prevent dementia and limit the progression of cognitive
      decline in later life are needed before these programs are adopted in normal
      routine clinical practice.

PMID- 21864012
TI  - Critically appraising qualitative research: a guide for clinicians more familiar
      with quantitative techniques.
AB  - OBJECTIVES: Papers using qualitative methods are increasingly common in
      psychiatric journals. This overview is an introduction to critically appraising a
      qualitative paper for clinicians who are more familiar with quantitative methods.
      CONCLUSIONS: Qualitative research uses data from interviews (semi-structured or
      unstructured), focus groups, observations or written materials. Data analysis is
      inductive, allowing meaning to emerge from the data, rather than the more
      deductive, hypothesis centred approach of quantitative research. This overview
      compares and contrasts quantitative and qualitative research methods.
      Quantitative concepts such as reliability, validity, statistical power, bias and
      generalisability have qualitative equivalents. These include triangulation,
      trustworthiness, saturation, reflexivity and applicability. Reflexivity also
      shares features of transference. Qualitative approaches include: ethnography,
      action-assessment, grounded theory, case studies and mixed methods. Qualitative
      research can complement quantitative approaches. An understanding of both is
      useful in critically appraising the psychiatric literature.

PMID- 21864013
TI  - Antiphospholipid syndrome following toxoplasma retinochoroiditis.
AB  - PURPOSE: To report a case of antiphospholipid syndrome (APS) following toxoplasma
      retinochoroiditis. DESIGN: Interventional case report. METHOD: The patient was a
      24-year-old female with an attack of visual loss due to toxoplasma
      retinochoroiditis concomitant with branch retinal vein occlusion. Retinitis
      resolved with anti-toxoplasma treatment. However, a recurrent episode of BRVO and
      vitreous hemorrhage occurred later. RESULT: In systemic evaluation, evidence of
      APS was detected, including high titers of anti-cardiolipin antibody, increased
      beta-2 microglobulin and anti-toxoplasma IgG antibody, and also low titers of C3,
      C4, and CH50. CONCLUSION: Ocular toxoplasmosis should be included in the list of
      etiologies of secondary APS. Systemic evaluation for detection of APS is a
      necessary approach to patients with toxoplasma retinochoroiditis and concomitant
      vascular accident.

PMID- 21864014
TI  - Comment on "Talent identification and promotion programmes of Olympic athletes".

PMID- 21864015
TI  - Limitations (and merits) of PENELOPE as a track-structure code.
AB  - PURPOSE: To outline the limitations of PENELOPE (acronym of PENetration and
      Energy LOss of Positrons and Electrons) as a track-structure code, and to comment
      on modifications that enable its fruitful use in certain microdosimetry and
      nanodosimetry applications. METHODS: Attention is paid to the way in which
      inelastic collisions of electrons are modelled and to the ensuing implications
      for microdosimetry analysis. RESULTS: Inelastic mean free paths and collision
      stopping powers calculated with PENELOPE and two well-known optical-data models
      are compared. An ad hoc modification of PENELOPE is summarized where ionization
      and excitation of liquid water by electron impact is simulated using tables of
      realistic differential and total cross sections. CONCLUSIONS: PENELOPE can be
      employed advantageously in some track-structure applications provided that the
      default model for inelastic interactions of electrons is replaced by suitable
      tables of differential and total cross sections.

PMID- 21864017
TI  - Performance of the Roche Accu-Chek active glucose meter to screen for gestational
      diabetes mellitus using fasting capillary blood.
AB  - BACKGROUND: Point-of-care (POC) blood glucose measurement using glucose meters is
      used by diabetes patients to mange their disease. POC glucose testing also is
      also used in tight glycemic control protocols and as a screening tool for
      diabetes. We report the performance and effectiveness of the Accu-Chek(r) Active
      (Roche Diagnostics GmbH, Mannheim, Germany) glucose meter to screen for
      gestational diabetes mellitus (GDM) using blood fasting capillary glucose (FCG).
      METHODS: To screen for GDM, 1,465 pregnant women underwent an oral glucose
      glucose tolerance test. Correlation between the FCG and fasting plasma glucose
      (FPG) levels was determined by Passing and Bablok regression analysis. Total
      error (TE) of the glucometer was ascertained using the Bland-Altman method with
      the DXC-800 analyzer (Beckman-Coulter Instruments, Brea, CA) as the reference
      method. The area under the receiver operator characteristic curve was used to
      analyze the performance of the FCG to predict GDM. RESULTS: FPG and FCG
      identified 361 (24.6%) and 338 (23%) women as having GDM, respectively. The Bland
      Altman TE at 95% limits of agreement was -11.1% to 10.8%. The area under the
      receiver operator characteristic curve was 0.953 (95% confidence interval 0.943
      to 0.964). CONCLUSIONS: The Roche Accu-Chek Active glucometer meets analytical
      and clinical quality requirements. A TE of+/-15% is acceptable for glucose meters
      used in ambulatory care, including home self-monitoring of blood glucose, and
      different TE targets should be set for acute critical care settings.

PMID- 21864016
TI  - Thrombocytopenia in childhood malaria with special reference to P. vivax
      monoinfection: A study from Bikaner (Northwestern India).
AB  - Thrombocytopenia is commonly seen in Plasmodium vivax malaria, but its prognostic
      value has not been addressed in children. This prospective study included 676
      admitted children of malaria [Plasmodium falciparum (Pf) monoinfection 262,
      Plasmodium vivax (Pv) monoinfection 380, and mixed (Pf + Pv) infection 34], in
      which thrombocytopenia (platelet count <150 * 10(3)/mm(3) on admission) was found
      in 442 (65.38%) children [Pf monoinfection 55.3% (145/262), Pv monoinfection
      73.16% (278/380), and mixed infection 55.88% (19/34)]. The association of
      thrombocytopenia was statistically significant with Pv monoinfection [73.16%
      (278/380)] in comparison to either Pf monoinfection [55.34% (145/262); odds ratio
      (OR) = 2.199 (95% confidence interval (CI) 1.577-3.068), p < 0.0001] or mixed
      infection [55.88% (19/34); OR = 2.152 (95%CI 1.054-4.394), p = 0.032]. In Pv
      monoinfection, thrombocytopenia was highest in 0-5 years age group and
      subsequently decreased with advancing age, whereas in Pf monoinfection it was
      reverse. Severe thrombocytopenia (platelet count <20 * 10(3)/mm(3)) was present
      in 16.52% (73/442) children [Pv monoinfection 21.58% (60/278) and Pf
      monoinfection 8.97% (13/145)]. The risk of developing severe thrombocytopenia was
      also highest in Pv monoinfection [15.79% (60/380)] in comparison to Pf
      monoinfection [10.59% (13/262); OR = 3.591 (95%CI 1.928-6.690), p < 0.0001].
      Bleeding manifestations were associated in 21.27% (94/442) children [Pf
      monoinfection 9.92% (26/262), Pv monoinfection 16.58% (63/380), and mixed malaria
      14.71% (5/34)]. All the children having bleeding manifestations had
      thrombocytopenia but low platelet counts were not always associated with abnormal
      bleeding. The association of severe malaria was significantly more among children
      having Pv monoinfection with platelet counts <20 * 10(3)/mm(3) [OR = 2.569 (95%CI
      1.196-5.517), p < 0.014] with specificity of 88.3% and positive predictive value
      of 85%. Till today, thrombocytopenia is not included in severe malaria criterion
      described by WHO, but when platelet counts <20 * 103/mm(3), we advocate it to
      include as one of the severe malaria criteria.

PMID- 21864018
TI  - A multiple local models approach to accuracy improvement in continuous glucose
      monitoring.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) devices estimate plasma glucose
      (PG) from measurements in compartments alternative to blood. The accuracy of
      currently available CGM is yet unsatisfactory and may depend on the implemented
      calibration algorithms, which do not compensate adequately for the differences of
      glucose dynamics between the compartments. Here we propose and validate an
      innovative calibration algorithm for the improvement of CGM performance. METHODS:
      CGM data from GlucoDay((r)) (A. Menarini, Florence, Italy) and paired reference
      PG have been obtained from eight subjects without diabetes during eu-, hypo-, and
      hyperglycemic hyperinsulinemic clamps. A calibration algorithm based on a dynamic
      global model (GM) of the relationship between PG and CGM in the interstitial
      space has been obtained. The GM is composed by independent local models (LMs)
      weighted and added. LMs are defined by a combination of inputs from the CGM and
      by a validity function, so that each LM represents to a variable extent a
      different metabolic condition and/or sensor-subject interaction. The inputs best
      suited for glucose estimation were the sensor current I and glucose estimations
      G, at different time instants [I(k), I(k)(-1), G(k)(-1)] (IIG). In addition to
      IIG, other inputs have been used to obtain the GM, achieving different
      configurations of the calibration algorithm. RESULTS: Even in its simplest
      configuration considering only IIG, the new calibration algorithm improved the
      accuracy of the estimations compared with the manufacturer's estimate: mean
      absolute relative difference (MARD)=10.8+/-1.5% versus 14.7+/-5.4%, respectively
      (P=0.012, by analysis of variance). When additional exogenous signals were
      considered, the MARD improved further (7.8+/-2.6%, P<0.05). CONCLUSIONS: The LM
      technique allows for the identification of intercompartmental glucose dynamics.
      Inclusion of these dynamics into the calibration algorithm improves the accuracy
      of PG estimations.

PMID- 21864019
TI  - A prefilled insulin pen with a novel injection mechanism and a lower injection
      force than other prefilled insulin pens.
AB  - BACKGROUND: FlexTouch((r)) (Novo Nordisk A/S, Bagsvaerd, Denmark) is a new
      prefilled insulin pen for people with diabetes, with a novel injection mechanism
      and no push-button extension at any dose setting. This study compared the
      injection force of FlexTouch with that of SoloStar((r)) (sanofi-aventis, Paris,
      France) and KwikPen((r)) (Eli Lilly & Co., Indianapolis, IN). METHODS: Injection
      force was measured with the manufacturers' recommended needle attached to each
      pen (NovoFine((r)) [Novo Nordisk] 32-gauge tip extra thin wall 6 mm needle for
      FlexTouch and BD [Franklin Lakes, NJ] MicroFineTM 31-gauge 5 mm needle for
      SoloStar and KwikPen) during injection of the maximum dose (60 IU for KwikPen and
      80 IU for FlexTouch and SoloStar). Injection was performed at three different
      constant push-button speeds. RESULTS: FlexTouch had a significantly (P<0.0001)
      lower injection force than SoloStar and KwikPen at all injection speeds. The
      mean+/-SD injection force of FlexTouch was 5.1+/-0.5 N. At 4, 6, and 8 mm/s push
      button speeds, the injection force of SoloStar was 13.5+/-2.1, 19.1+/-1.9, and
      26.9+/-2.4 N, respectively, and the injection force of KwikPen was 14.5+/-1.9,
      20.9+/-1.4, and 28.2+/-1.4 N, respectively. CONCLUSIONS: The injection mechanism
      of FlexTouch means that insulin injection is driven by a torque spring and not
      the thumb pressure of the user. This results in a 62-82% lower injection force
      with FlexTouch than other prefilled insulin pens.

PMID- 21864020
TI  - Chlamydia and chronic arthritis.
AB  - Certain bacterial infections have been demonstrated to be causative of reactive
      arthritis. The most common bacterial trigger of reactive arthritis is Chlamydia
      trachomatis. Chlamydia pneumoniae is another known cause, albeit far less
      frequently. Although Chlamydia-induced reactive arthritis will often
      spontaneously remit, approximately 30% of patients will develop a chronic course.
      Modern medicine has provided rather remarkable advances in our understanding of
      the chlamydiae, as these organisms relate to chronic arthritis and the delicate
      balance between host and pathogen. C. trachomatis and C. pneumoniae both have a
      remarkable ability to disseminate from the initial site of infection and
      establish persistently viable organisms in distant organ sites, namely the
      synovial tissue. How these persistent chlamydiae contribute to disease
      maintenance remains to be fully established, but recent data demonstrating that
      long-term combination antimicrobial treatment can not only ameliorate the
      symptoms but eradicate the persistent infection suggest that these chronically
      infecting chlamydiae are indeed a driving force behind the chronic inflammation.
      We are beginning to learn that this all appears possible even after an
      asymptomatic initial chlamydial infection. Both C. trachomatis and C. pneumoniae
      are a clear cause of chronic arthritis in the setting of reactive arthritis; the
      possibility remains that these same organisms are culpable in other forms of
      chronic arthritis as well.

PMID- 21864021
TI  - New anticoagulants: moving on from scientific results to clinical implementation.
AB  - Vitamin K antagonists (VKA) are the only registered oral anticoagulants for the
      treatment of venous thromboembolism (VTE). VKA have an unpredictable and highly
      variable effect on coagulation, with a high risk of under- and over-treatment.
      Novel anticoagulants, such as dabigatran and rivaroxaban, could be a very welcome
      replacement for VKA, as they show a predictable anticoagulant effect. Results of
      several phase II and III studies have shown the efficacy and safety of dabigatran
      and rivaroxaban in the prophylaxis and treatment of VTE, and for the prevention
      of stroke in atrial fibrillation. It remains to be shown whether these new
      anticoagulants have the same safety profile in daily clinical practice, where
      more vulnerable patients will be treated. Lack of information on the proper
      monitoring method or antidote in case of bleeding may also hinder the translation
      from science to clinical practice.

PMID- 21864022
TI  - Differential antibacterial activity against Pseudomonas aeruginosa by carbon
      monoxide-releasing molecules.
AB  - AIMS: Carbon monoxide (CO) delivered in a controlled manner to cells and
      organisms mediates a variety of pharmacological effects to the extent that CO
      releasing molecules (CO-RMs) are being developed for therapeutic purposes.
      Recently, ruthenium-based CO-RMs have been shown to posses important bactericidal
      activity. Here we assessed the effect of fast CO releasers containing ruthenium
      (Ru(CO)(3)Cl(glycinate) [CORM-3] and tricarbonyldichlororuthenium(II) dimer [CORM
      2]) and a novel slow manganese-based CO releaser
      ([Me(4)N][Mn(CO)(4)(thioacetate)(2)] [CORM-371]) on O(2) consumption and growth
      of Pseudomonas aeruginosa (PAO1). We then compared these effects with the action
      elicited by sodium boranocarbonate (CORM-A1), which lacks a transition metal but
      liberates CO with a rate similar to CORM-371. RESULTS: CORM-2, CORM-3, and, to a
      lesser extent, CORM-371 exerted a significant bactericidal effect and decreased
      O(2) consumption in PAO1 in vitro. The effect appeared to be independent of
      reactive oxygen species production, but in the case of metal-containing compounds
      it was prevented by the thiol donor N-acetylcysteine. In contrast, CORM-A1 was
      bacteriostatic rather than bactericidal in vitro eliciting only a moderate and
      transient decrease in O(2) consumption. INNOVATION: None of the tested CO-RMs was
      toxic to murine macrophages or human fibroblasts at the concentration impairing
      PA01 growth but only ruthenium-containing CO-RMs showed potential therapeutic
      properties by increasing the survival of mice infected with PA01. CONCLUSION: CO
      carriers inhibit bacterial growth and O(2) consumption in vitro, but transition
      metal carbonyls appear more powerful than compounds spontaneously liberating CO.
      The nature of the metal in CO-RMs also modulates the anti-bacterial effect, with
      ruthenium-based CO-RMs being efficacious both in vitro and in vivo.

PMID- 21864023
TI  - Antioxidants and self-reported history of kidney stones: the National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND AND PURPOSE: Animal studies have demonstrated the likely role of
      oxidative tissue damage in the pathophysiology of stone disease; however, the
      effect of antioxidants on stone formation in the human population is unknown. We
      evaluated the association between serum antioxidant levels and the self-reported
      prevalence of kidney stones in a large cross-sectional population in a
      retrospective cohort study. MATERIALS AND METHODS: Serum levels of antioxidants
      among adult participants in the National Health and Nutrition Examination Survey
      (NHANES III) 1988-1994 were compared between those with and without a self
      reported history of kidney stones, adjusting for covariates of age, sex, body
      mass index (BMI), race/ethnicity, diabetes, and hypertension. RESULTS: The
      prevalence of kidney stones was 5.25% (95% confidence interval: 4.60%, 5.90%).
      The prevalence of kidney stones was higher in males, white/non-Hispanics,
      diabetics, and those with hypertension. The prevalence of kidney stones increased
      with BMI. After adjusting for covariates, mean levels of alpha-carotene, beta
      carotene, and beta-cryptoxanthin were significantly lower in those with kidney
      stones (-9.36%, -10.79%, and -8.48%, respectively). When analyzed by quartile,
      higher serum levels of beta-carotene and beta-cryptoxanthin,, trended toward a
      decreasing prevalence of stones (P=0.007 and P=0.03, respectively), indicating
      that the highest levels of these antioxidants may protect against the formation
      of kidney stones. CONCLUSIONS: Lower levels of alpha-carotene, beta-carotene, and
      beta-cryptoxanthin are associated with a history of kidney stones and may
      indicate a role for these antioxidants in preventing stone formation.

PMID- 21864024
TI  - Hand-assisted laparoscopic partial nephrectomy without formal collecting system
      closure: perioperative outcomes in 104 consecutive patients.
AB  - BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) paralleling open
      techniques, particularly closure of the collecting system, can be technically
      challenging for the novice laparoscopist. We describe operative results and
      complications of a single surgeon, retrospectively reviewed series using a
      simplified method of hand assistance and a fibrin glue patch for hemostasis
      without formal collecting system closure. PATIENTS AND METHODS: We identified 104
      consecutive patients between September 2003 and January 2009 who underwent hand
      assisted laparoscopic partial nephrectomy (HALPN). Our technique involves routine
      hilar clamping after isolation of the tumor and mobilization of the kidney. After
      resection of the mass, a fibrin glue patch is placed within the surgical defect
      and secured with bolstering sutures. No attempt is made to suture the collecting
      system, nor are ureteral catheters placed when the collecting system is entered
      during resection of the tumor. RESULTS: Mean tumor size was 2.8 cm (median 2.5
      cm, range 0.7-7.0 cm). With hilar clamping, warm ischemia time averaged 24.5
      minutes (range 11-39 min). Estimated blood loss averaged 220 mL (range 50-1500
      mL), and five (4.8%) patients received transfusions either intraoperatively or
      postoperatively. Urine leak occurred in 1.9% (n=2) of patients overall and 4.3%
      (2/47) of patients with documented collecting system entry. Both urine leaks
      resolved with conservative management only. CONCLUSIONS: HALPN without formal
      collecting system closure is a safe and effective technique with similar urine
      leak and transfusion rates compared with other series. This technique may allow
      more urologists to perform minimally invasive partial nephrectomy or to do so
      with potentially shorter ischemia times.

PMID- 21864025
TI  - Standardized linear port configuration to improve operative ergonomics in
      laparoscopic renal and adrenal surgery: experience with 1264 cases.
AB  - BACKGROUND AND PURPOSE: Traditional laparoscopic port placement for upper urinary
      tract surgery involves camera access via the umbilicus with working ports placed
      on either side of the camera at various locations. This diamond configuration
      requires the camera operator to cross hands with the surgeon, resulting in poor
      ergonomics. A standardized linear port configuration has been used for nearly all
      transperitoneal urologic surgery at our institution. The purpose of this article
      is to describe our experience with this simplified approach and its advantages.
      PATIENTS AND METHODS: A retrospective review was conducted of all laparoscopic
      cases by a single surgeon from 2000 to June 2009. The linear port configuration
      includes three ports placed along the ipsilateral pararectal line with the most
      superior port one fingerbreadth below the costal margin and the inferior port at
      the level of the umbilicus. A 5-mm camera is used through the most superior port.
      A low transverse extraction site is typically used, if necessary. RESULTS: There
      were 1264 laparoscopic cases performed using the linear port configuration. Of
      these, there were 1038 donor/radical/simple and 60 partial nephrectomies, 35
      nephroureterectomies, 49 adrenalectomies, 50 pyeloplasties, 20 renal
      cryoablations, and 12 miscellaneous renal procedures. Of these, 98.2% were
      performed successfully via this port configuration. Three cases needed an
      additional port. The intraoperative complication rate was 0.9%, and mean
      estimated blood loss was 60 mL. There were 20 (1.6%) open conversions: 16 were
      elective and 4 secondary to complications. CONCLUSION: Simplifying port placement
      via a linear configuration for both right and left renal and adrenal surgery is
      feasible, easy to learn, simplifies strategic planning preoperatively, and
      provides excellent exposure. Using camera access through the superior port allows
      for direct visualization and minimizes interaction between the camera holder and
      surgeon's working envelope.

PMID- 21864026
TI  - Initial experience of laparoendoscopic single-site nephroureterectomy with
      bladder cuff excision for upper urinary tract urothelial carcinoma performed by a
      single surgeon.
AB  - PURPOSE: To present our experience with the first 10 consecutive cases of
      laparoendoscopic single-site nephroureterectomy (LESSNU) with bladder cuff
      excision for upper tract urothelial carcinoma. PATIENTS AND METHODS: Ten patients
      (6 men and 4 women; 6 renal pelvis and 4 ureter) underwent LESSNU by a single
      surgeon. We made a 4-cm single incision at the umbilicus using a homemade single
      port device. The single-port device was made with a surgical glove and Alexis
      wound retractor. LESSNU was performed by the same technique of conventional
      laparoscopic NU. RESULTS: The mean age was 62.79 +/- 7.93 years. The mean total
      operative time, time for nephrectomy, and time for bladder cuff excision were
      225.6 +/- 365.87, 80.00 +/- 29.03, and 145.63 +/- 42.63 minutes. The mean
      estimated blood loss was 187.50 +/- 83.45 mL. On surgical pathologic examination,
      four patients were pT(1)N(0), four patients were pT(2)N(0), one patient was
      pT(3)N(0), and one patient was pT(3)N(2). There was one positive surgical margin
      in a pT(3)N(2) patient. The mean number of lymph nodes dissected was 2.5 (range 0
      9). One incision extension was performed because of complete renal hilar
      lymphadenectomy by open technique (for the pT(3)N(2) patient), and one open
      conversion with a Gibson incision was performed because of severe adhesions
      around the distal ureter (the pT(3)N(0) patient). There were one case of
      transient ileus and one of fever that were improved with conservative treatment.
      The mean hospital stay was 4.75 +/- 3.37 days. Eight patients who underwent
      LESSNU successfully were satisfied with their operations. CONCLUSIONS: LESSNU for
      upper urinary tract urothelial carcinoma seems to be feasible and safe, but it is
      still challenging for advanced cases.

PMID- 21864027
TI  - Re: Reduced radiation exposure with the use of an air retrograde pyelogram during
      fluoroscopic access for percutaneous nephrolithotomy (from: Lipkin ME, Mancini
      JG, Zilberman DE, et al. J Endourol 2011;25:563-567).

PMID- 21864028
TI  - The role of Tyk2 in regulation of breast cancer growth.
AB  - The antigrowth and immunomodulatory actions of interferons (IFNs) have enabled
      these cytokines to be used therapeutically for the treatment of a variety of
      hematologic and solid malignancies. IFNs exert their effects by activation of the
      Jak/Stat signaling pathway. IFNgamma stimulates the tyrosine kinases Jak1 and
      Jak2, resulting in activation of the Stat1 transcription factor, whereas type 1
      IFNs (IFNalpha/beta) activate Jak1 and Tyk2, which mediate their effects through
      Stat1 and Stat2. Disruption in the expression of IFNgamma, IFNalpha receptors, or
      Stat1 inhibits antitumor responses and blunt cancer immunosurveillance in mice.
      Mutations in Jak2 or constitutive activation of Jak1 or Jak2 also promote the
      development of a variety of malignancies. Although there are data indicating that
      Tyk2 plays a role in the pathogenesis of lymphomas, the effects of Tyk2
      expression on tumorigenesis are unknown. We report here that Tyk2(-/-) mice
      inoculated with 4T1 breast cancer cells show enhanced tumor growth and metastasis
      compared to Tyk2(+/+) animals. Accelerated growth of 4T1 cells in Tyk2(-/-)
      animals does not appear to be due to decreased function of CD4(+), CD8(+) T
      cells, or NK cells. Rather, the tumor suppresive effects of Tyk2 are mediated at
      least in part by myeloid-derived suppressor cells, which appear to be more
      effective in inhibiting T cell responses in Tyk2(-/-) mice. Our results provide
      the first evidence for a role of Tyk2 in suppressing the growth and metastasis of
      breast cancer.

PMID- 21864029
TI  - Complete mitochondrial genome of Chilo suppressalis (Walker) (Lepidoptera:
      Crambidae).
AB  - The complete sequence of the mitochondrial genome (mitogenome) of the rice stem
      borer Chilo suppressalis (Walker) (Lepidoptera: Crambidae) was determined to be
      15,465 bp. It contains 13 protein-coding genes (PCGs), 22 tRNA genes, the large
      and small rRNA genes, and an A+T-rich region. The nucleotide composition of the
      mitogenome of C. suppressalis is highly A+T biased, accounting for 79.70% in
      whole mitogenome, 77.74% in PCGs, 84.70% in tRNAs, 81.20% in rRNAs and 94.19% in
      A+T-rich region, respectively. The PCGs have typical ATN start codons, except for
      cox1, which contains the unusual CGA. The C. suppressalis A+T-rich region
      contains a conserved structure combining the motif ATAGA and a 19-bp poly-T
      stretch, but absence of the 9-bp poly-A element upstream trnM.

PMID- 21864030
TI  - Complete mitochondrial genome sequence of the Chinese scrub vole (Neodon irene).
AB  - The Chinese scrub vole (Neodon irene) belongs to the subfamily Arvicolinae, which
      is restricted to mountain areas at high altitudes (2800-4000). In this study, we
      sequenced the complete mitochondrial genome of N. irene. It was determined to be
      16,367 bases. The nucleotide sequence data of 12 heavy-strand protein-coding
      genes of N. irene and other 22 rodents were used for phylogenetic analysis.
      Bayesian inference (BI) and maximum likelihood (ML) were used. Both the BI and ML
      trees demonstrated that Microtus rossiaemeridionalis and Microtus kikuchii did
      not cluster together with each other. On the contrary, M. rossiaemeridionalis
      showed close relationship with N. irene. In the present study, only one sequence
      from Neodon and two sequences from Microtus were included in the phylogenetic
      analysis which should contribute to the unusual relationship. Therefore, in order
      to better understand the phylogenetic relationship within Rodentia, more rodents'
      complete mitochondrial genomes are required.

PMID- 21864031
TI  - Complete mitochondrial genome of the Seoul frog Rana chosenica (Amphibia,
      Ranidae): comparison of R. chosenica and R. plancyi.
AB  - Here, we have sequenced the complete mitochondrial genome of the Seoul frog Rana
      chosenica (Amphibia, Ranidae), which is known as a Korean endemic species. It is
      listed as a vulnerable species by IUCN Red List and also an endangered species in
      South Korea. The complete mitochondrial genome of R. chosenica consists of 18,357
      bp. Its gene arrangement pattern was identical with those of other Rana frogs. We
      compared the mitochondrial genome of R. chosenica with that of the Peking frog
      Rana plancyi that has been known closely related to R. chosenica. Nucleotide
      sequence similarity between the two whole mitochondrial genomes was 95.7%, and
      the relatively low similarity seems to indicate that the two species are
      distinctly separated on the species level. The information of mitochondrial
      genome comparison of the two species was discussed in detail.

PMID- 21864032
TI  - Effect of different sampling strategies for a single geographic region in Yemen
      on standard genetic analyses of mitochondrial DNA sequence data.
AB  - Collection of biological samples is the foundation of genetic studies ranging
      from estimation of genetic diversity to reconstruction of population history.
      Sample collections are intended to accurately represent the genetic, biological,
      ecological, cultural, geographic, and/or linguistic diversity of a particular
      region or population by providing a small, but representative, set of samples. In
      this study, we analyze human mitochondrial DNA variation in samples collected
      using four different sampling strategies to represent the same geographic region.
      Specifically, samples were collected from a village, a rural area, a regional
      clinic, and a national university in the governorate of Dhamar in Yemen. All
      samples were assayed for mitochondrial hypervariable region I DNA sequence
      variation and data were subjected to standard molecular genetic analyses. Our
      results suggest that analyses in which individual DNA sequences are explicitly
      compared or evaluated, e.g. phylogenetic and network analyses, may be more
      sensitive to sample collection design than analyses in which data are averaged
      across individuals or are analyzed more indirectly, e.g. summary statistics.

PMID- 21864033
TI  - Divergent effects of compounds on the hydrolysis and transpeptidation reactions
      of gamma-glutamyl transpeptidase.
AB  - A novel class of inhibitors of the enzyme gamma-glutamyl transpeptidase (GGT)
      were evaluated. The analog OU749 was shown previously to be an uncompetitive
      inhibitor of the GGT transpeptidation reaction. The data in this study show that
      it is an equally potent uncompetitive inhibitor of the hydrolysis reaction, the
      primary reaction catalyzed by GGT in vivo. A series of structural analogs of
      OU749 were evaluated. For many of the analogs, the potency of the inhibition
      differed between the hydrolysis and transpeptidation reactions, providing insight
      into the malleability of the active site of the enzyme. Analogs with electron
      withdrawing groups on the benzosulfonamide ring, accelerated the hydrolysis
      reaction, but inhibited the transpeptidation reaction by competing with a
      dipeptide acceptor. Several of the OU749 analogs inhibited the transpeptidation
      reaction by slow onset kinetics, similar to acivicin. Further development of
      inhibitors of the GGT hydrolysis reaction is necessary to provide new therapeutic
      compounds.

PMID- 21864034
TI  - Long-term maintenance of glucose control in veterans with type 2 diabetes
      mellitus using oral agents.
AB  - PURPOSE OF STUDY: The aim of this study was to evaluate long-term glycemic
      control in individuals with type 2 diabetes mellitus on oral hypoglycemic agents.
      METHODS: We identified the cohort of veterans prescribed hypoglycemic agents
      every year from July, 1992, through June, 2007 (n=191). Glycosylated hemoglobin
      (HbA1c) was used to assess glycemic control. Data are expressed as mean+/
      standard deviation (SD); statistics are expressed by t-test and chi-squared.
      P<0.05 was considered significant. RESULTS: In the first year, 96 of the select
      group of 191 veterans identified above received oral agents only (OAO), 74
      insulin only, and 21 both insulin and oral agents. Fifteen years later, 59 were
      OAO, 78 insulin only, and 54 both. Six patients receiving insulin in 1992-1993
      were OAO-treated in 2006-2007. In the subgroup on OAO both at baseline and at the
      end (n=53), HbA1c decreased from 7.89+/-1.21 to 7.09+/-1.13 (P<0.001). These
      veterans were older at baseline (62.4+/-6.2) and leaner at the 15-year follow-up
      [body mass index (BMI) 28.1+/-4.9] than those who received insulin in 2006-2007
      (n=43; age=57.9+/-9.6; BMI=32.3+/-7.9; P<0.05 and 0.005, respectively). Patients
      in the stable OAO group (n=53) were 74.0% Caucasian, compared to 51.2% in former
      OAO [n=43; P<0.05 (chi-squared)]. CONCLUSIONS: Over half (n=53; 55%) of patients
      originally in the OAO group remained so 15 years later. These stable patients
      were in better glycemic control, both at baseline and follow-up, less obese,
      older, and more likely to be Caucasian, than those who eventually received
      insulin. Currently used oral agents often maintain, or even improve, glucose
      control, over 2 decades after diagnosis of diabetes mellitus.

PMID- 21864035
TI  - Long-term survival after allogeneic stem cell transplant for relapsed large B
      cell lymphomas: a retrospective study.

PMID- 21864036
TI  - The impact of high-dose chemotherapy, autologous stem cell transplant and
      conventional chemotherapy on quality of life of long-term survivors with
      follicular lymphoma.
AB  - In this study we investigated the quality of life (QoL) of long-term survivors
      with follicular lymphoma (FL) after high-dose chemotherapy (HDCT) and autologous
      stem cell transplant (ASCT) using two standardized questionnaires. Altogether,
      124 patients with FL were included in the study. A total of 63 patients received
      HDCT with ASCT, and this group was compared with 61 patients who were treated
      with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
      chemotherapy and supplementary radiation. In addition, the QoL of the patients
      was compared to the QoL of healthy people on the basis of two studies about the
      general health status of the German population. When the QoLs of the HDCT group
      and the conventional therapy group were compared, there was a tendency for better
      QoL in the HDCT group, maybe due to a higher proportion of patients in complete
      remission (CR) or a longer follow-up period in the HDCT group (8.5 years vs. 4.5
      years in the conventional therapy group). In both the HDCT group and the
      conventional therapy group, the results of the questionnaires showed a reduced
      QoL compared to the healthy population. In this study, there was a tendency for
      better QoL in the HDCT group compared to the conventional therapy group. However,
      the negative impact of both HDCT and conventional therapy on the QoL of patients
      with follicular lymphoma should not be underestimated and should lead to the
      development of less toxic therapy strategies.

PMID- 21864037
TI  - Up-regulated autophagy by endogenous high mobility group box-1 promotes
      chemoresistance in leukemia cells.
AB  - Autophagy has recently attracted increasing attention for its role in conferring
      resistance to various commonly used anticancer therapies. Whereas its activities
      are known primarily to be under regulation of the high mobility group box-1
      (HMGB1) gene, the expression of HMGB1 and its function in leukemia cells still
      remain unclear. In this study, we found that HMGB1 was expressed abundantly in
      various kinds of both leukemia and non-blood cancer cell-lines, and its
      expression was positively correlated with clinical status in childhood leukemia.
      In leukemia cells, when endogenous HMGB1 increased starvation-induced autophagy,
      this reaction was inhibited by the suppression of HMGB1. While the use of
      autophagy inhibitor, 3-methyladenine (3-MA), blocked the autophagic reaction and
      increased leukemia cell sensitivity to chemotherapy, enhancing HMGB1 expression
      decreased this sensitivity. Notably, suppressing HMGB1 expression also increased
      leukemia cell chemosensitivity. Furthermore, the phosphatidylinositol 3-kinase
      (PI3K)/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway was found to
      be functionally connected with HMGB1. HMGB1 gene transfection increased the LC3
      II level and inhibited phosphorylation of Akt and p70S6K levels. Knockdown of
      HMGB1 expression blocked the association between mTOR and raptor in the setting
      of enhanced autophagy. When class I PI3K was inhibited by PI3K-I shRNA, it
      decreased the PI3K-I expression level. Knockdown of HMGB1 expression had no
      further effects on LC3-II. These results suggest that endogenous HMGB1 is an
      intrinsic regulator of autophagy in leukemia cells and it enhances leukemia cell
      chemoresistance likely through the PI3K/Akt/mTORC1 pathway.

PMID- 21864038
TI  - Myasthenia gravis, an autoimmune manifestation of lymphoma and
      lymphoproliferative disorders: case reports and review of literature.
AB  - Myasthenia gravis (MG) is an autoimmune disease mediated by antibodies to
      acetylcholine receptors (AChRs) or muscle specific tyrosine kinase (MuSK). While
      the frequent association of MG with thymoma in patients aged 40-60 years is well
      recognized, its occurrence in patients with lymphoma has not been well studied.
      We review the literature on the association of MG and lymphoid malignancies and
      report two new patients. MG can occur in a synchronous or non-synchronous fashion
      with lymphoma. The pathogenesis of MG in lymphoid malignancies is probably
      heterogeneous and likely relates to perturbations in the immune mechanisms that
      normally prevent the emergence of autoimmunity. These perturbations could be the
      result of the lymphoid malignancy per se, or its treatment.

PMID- 21864039
TI  - Improved outcome for very elderly patients with diffuse large B-cell lymphoma in
      the immunochemotherapy era.
AB  - The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved significantly
      since the introduction of immunochemotherapy (rituximab [R] with
      cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP]). However, few
      outcome data are available for very elderly patients (>= 80 years). Therefore, we
      compared all patients with DLBCL aged >= 80 years diagnosed in the Gothenburg
      area during two time periods (2006-2009, "post-R" and 1997-2000, "pre-R"). Forty
      and 30 patients were identified, corresponding to 23.5% and 20.5%, respectively,
      of the entire population with DLBCL. Estimated 3-year progression-free (PFS) and
      overall (OS) survival was better post-R than pre-R: 41% vs. 17% (p = 0.015) and
      41% vs. 17% (p = 0.01), respectively. Fifty-three percent of post-R patients were
      treated with curative intent with a moderately reduced R-CHOP regimen (median
      relative dose intensity: 0.86). At a median follow-up of 29 months, the 3-year
      PFS and OS were 70% (p = 0.018) and 76% (p = 0.0089), respectively. In
      conclusion, moderately reduced R-CHOP is tolerable and effective for a
      considerable number of very elderly patients with DLBCL and high age by itself
      should not be a reason for excluding a patient with DLBCL from such treatment.

PMID- 21864040
TI  - Rituximab plus 70% cyclophosphamide, doxorubicin, vincristine and prednisone for
      Japanese patients with diffuse large B-cell lymphoma aged 70 years and older.
AB  - In the rituximab era, several large studies have suggested that full-dose
      rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)
      might be the best treatment for patients with diffuse large B-cell lymphoma
      (DLBCL) aged 60 years and older. However, it remains unclear whether this is also
      the case for those aged 70 years and older. Previously untreated patients with
      DLBCL aged 70 years and older (elderly) were treated with R-70%CHOP, and patients
      younger than 70 years (younger) were treated with full-dose R-CHOP every 3 weeks,
      for a total of 6-8 cycles. Complete remission (CR) rates in elderly versus
      younger patients were 75 vs. 78% (p = 0.7), respectively. The 3-year overall
      survival, event-free survival and progression-free survival of elderly versus
      younger patients were 58 vs. 78% (p < 0.05), 45 vs. 70% (p < 0.05) and 64 vs. 72%
      (p = 0.43), respectively. Severe adverse events were more frequent in the
      elderly, even with the dose reduction in that age group. Three-year PFS with R
      70%CHOP for patients aged 70 years and older was not significantly worse than
      that with full-dose R-CHOP for younger patients, suggesting that R-70% CHOP might
      be a reasonable choice for patients with DLBCL aged 70 years and older,
      especially for those with comorbidities.

PMID- 21864041
TI  - Targeting Waldenstrom macroglobulinemia with histone deacetylase inhibitors.

PMID- 21864042
TI  - Maintenance rituximab following induction chemo-immunotherapy for mantle cell
      lymphoma: long-term follow-up of a pilot study from the Wisconsin Oncology
      Network.
AB  - Mantle cell lymphoma (MCL) is challenging to manage, with a median survival of 3
      5 years. While intensive strategies are often appropriate for younger patients,
      these approaches are often not appropriate for older patients. In 2006, we
      reported our initial results using modified R-hyperCVAD (rituximab with
      hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone)
      with maintenance rituximab. The complete response rate was 64%, and median
      progression-free survival (PFS) 37 months. Herein, we update our results, now
      with a median follow-up of 62 months. The median PFS is unchanged and the median
      overall survival (OS) is 70 months. The proportion of patients surviving at 5
      years is 62%, comparable to studies using intensive strategies in similar patient
      populations. No late toxicities were noted in our cohort. These long-term results
      suggest that the modified R-hyperCVAD regimen with maintenance rituximab is an
      excellent option for older patients with newly diagnosed mantle cell lymphoma.

PMID- 21864043
TI  - Allogeneic hematopoietic cell transplant for multiple myeloma using reduced
      intensity conditioning therapy, 1998-2006: factors associated with improved
      survival outcome.
AB  - This study reports on the outcome of 95 allogeneic hematopoietic cell transplants
      (HCTs) using reduced intensity conditioning (RIC) performed for patients with
      multiple myeloma (MM) in Australia and New Zealand between 1998 and 2006. The
      median age at HCT was 52 years. Of the 32 patients for whom the allograft was
      performed as a first transplant, 15 (47%) had their allograft less than 1 year
      from diagnosis, while for the 63 patients who had an allograft following an
      autograft, nine (14%) were allografted within 1 year post-diagnosis (p < 0.001).
      The cumulative incidence of transplant-related mortality (TRM) was 19% at 1 year
      post-transplant. At 5 years post-transplant the overall survival (OS) was 40% and
      progression-free survival (PFS) was 23%, with no apparent survival plateau. Three
      factors were independently favorable predictors of OS in a Cox regression model:
      immunoglobulin G (IgG) myeloma (hazard ratio [HR] = 0.42, 95% confidence interval
      [CI] 0.24-0.75, p = 0.004), a human leukocyte antigen (HLA)-identical sibling
      donor (HR = 0.37, 95% CI 0.18-0.74, p = 0.005), and less than 1 year between MM
      diagnosis and RIC HCT (HR = 0.27, 95% CI 0.12-0.59, p = 0.001). Patterns of
      outcome indicate that RIC HCT may offer the potential for cure for only a small
      group of patients with MM.

PMID- 21864044
TI  - Phytoplasma-induced floral abnormalities in Catharanthus roseus are associated
      with phytoplasma accumulation and transcript repression of floral organ identity
      genes.
AB  - Floral symptoms caused by phytoplasma largely resemble floral reversion in other
      plants. Periwinkle leaf yellowing (PLY) phytoplasma and peanut witches'-broom
      (PnWB) phytoplasma caused different degrees of floral abnormalities on infected
      periwinkle plants. The PLY phytoplasma-infected plants exhibited floral
      discoloration, virescence, small flowers, and only occasionally full floral
      reversion. In contrast, PnWB phytoplasma frequently induced complete floral
      reversion and resulted in a witches'-broom symptom from the floral reversion.
      Although different degrees of floral symptoms were induced by these two
      phytoplasmas, the morphological disorders were similar to those of other plants
      carrying SEPALLATA mutations or gene silencing. Here, we compared expression
      levels of organ-identity-related genes and pigmentation genes during floral
      symptom development. Accumulation of phytoplasmas in malformed flowers and their
      closely surrounding leaves was also compared. In infected plants, transcript
      abundance of all examined organ identity genes and pigmentation genes was
      suppressed. Indeed, CrSEP3, a SEPALLALA3 ortholog, showed the greatest
      suppression among genes examined. Of the pigmentation genes, transcript reduction
      of chalcone synthase was most highly correlated with the loss in floral
      pigmentation. Floral symptom severities were associated with the accumulation of
      either phytoplasmas. Interestingly, both phytoplasmas accumulated to higher
      levels in malformed flowers than in their surrounding leaves. Many plant
      pathogens manipulate host plant development to their advantage. It is intriguing
      to see whether phytoplasmas alter floral development to increase their
      population.

PMID- 21864045
TI  - Photosynthetic Bradyrhizobium Sp. strain ORS285 synthesizes 2-O-methylfucosylated
      lipochitooligosaccharides for nod gene-dependent interaction with Aeschynomene
      plants.
AB  - Bradyrhizobium sp. strain ORS285 is a photosynthetic bacterium that forms
      nitrogen-fixing nodules on the roots and stems of tropical aquatic legumes of the
      Aeschynomene genus. The symbiotic interaction of Bradyrhizobium sp. strain ORS285
      with certain Aeschynomene spp. depends on the presence of nodulation (nod) genes
      whereas the interaction with other species is nod gene independent. To study the
      nod gene-dependent molecular dialogue between Bradyrhizobium sp. strain ORS285
      and Aeschynomene spp., we used a nodB-lacZ reporter strain to monitor the nod
      gene expression with various flavonoids. The flavanones liquiritigenin and
      naringenin were found to be the strongest inducers of nod gene expression.
      Chemical analysis of the culture supernatant of cells grown in the presence of
      naringenin showed that the major Nod factor produced by Bradyrhizobium sp. strain
      ORS285 is a modified chitin pentasaccharide molecule with a terminal N-C(18:1)
      glucosamine and with a 2-O-methyl fucose linked to C-6 of the reducing
      glucosamine. In this respect, the Bradyrhizobium sp. strain ORS285 Nod factor is
      the same as the major Nod factor produced by the nonphotosynthetic Bradyrhizobium
      japonicum USDA110 that nodulates the roots of soybean. This suggests a classic
      nod gene-dependent molecular dialogue between Bradyrhizobium sp. strain ORS285
      and certain Aeschynomene spp. This is supported by the fact that B. japonicum
      USDA110 is able to form N(2)-fixing nodules on both the roots and stems of
      Aeschynomene afraspera.

PMID- 21864046
TI  - The Arabidopsis thaliana DNA-binding protein AHL19 mediates verticillium wilt
      resistance.
AB  - Verticillium spp. are destructive soilborne fungal pathogens that cause vascular
      wilt diseases in a wide range of plant species. Verticillium wilts are
      particularly notorious, and genetic resistance in crop plants is the most
      favorable means of disease control. In a gain-of-function screen using an
      activation-tagged Arabidopsis mutant collection, we identified four mutants, A1
      to A4, which displayed enhanced resistance toward the vascular wilt species
      Verticillium dahliae, V. albo-atrum and V. longisporum but not to Fusarium
      oxysporum f. sp. raphani. Further testing revealed that mutant A2 displayed
      enhanced Ralstonia solanacearum resistance, while mutants A1 and A3 were more
      susceptible toward Pseudomonas syringae pv. tomato. Identification of the
      activation tag insertion site in the A1 mutant revealed an insertion in close
      proximity to the gene encoding AHL19, which was constitutively expressed in the
      mutant. AHL19 knock-out alleles were found to display enhanced Verticillium
      susceptibility whereas overexpression of AHL19 resulted in enhanced Verticillium
      resistance, showing that AHL19 acts as a positive regulator of plant defense.

PMID- 21864047
TI  - Whole-genome expression profiling of Bradyrhizobium japonicum in response to
      hydrogen peroxide.
AB  - Bradyrhizobium japonicum, a nitrogen-fixing bacterium in soil, establishes a
      symbiotic relationship with the leguminous soybean plant. Despite a mutualistic
      association between the two partners, the host plant produces an oxidative burst
      to protect itself from the invasion of rhizobial cells. We investigated the
      effects of H(2)O(2)-mediated oxidative stress on B. japonicum gene expression in
      both prolonged exposure (PE) and fulminant shock (FS) conditions. In total, 439
      and 650 genes were differentially expressed for the PE and FS conditions,
      respectively, at a twofold cut-off with q < 0.05. A number of genes within the
      transport and binding proteins category were upregulated during PE and a majority
      of those genes are involved in ABC transporter systems. Many genes encoding ?
      factors, global stress response proteins, the FixK(2) transcription factor, and
      its regulatory targets were found to be upregulated in the FS condition.
      Surprisingly, catalase and peroxidase genes which are typically expressed in
      other bacteria under oxidative stress were not differentially expressed in either
      condition. The isocitrate lyase gene (aceA) was induced by fulminant H(2)O(2)
      shock, as was evident at both the transcriptional and translational levels.
      Interestingly, there was no significant effect of H(2)O(2) on exopolysaccharide
      production at the given experimental conditions.

PMID- 21864048
TI  - Muir-Torre syndrome - an uncommon localization of sebaceous carcinomas following
      irradiation.

PMID- 21864049
TI  - Is genetic counseling a stressful event?
AB  - PURPOSE: The aim of this paper was to investigate whether cancer genetic
      counseling could be considered as a stressful event and associated with more
      anxiety and/or depression compared to other cancer-related events for instance
      attending mammography screening or receiving a cancer diagnosis. METHODS: A total
      of 4911 individuals from three Scandinavian countries were included in the study.
      Data was collected from individuals who had attended either cancer genetic
      counseling (self-referred and physician-referred) or routine mammography
      screening, were recalled for a second mammograpy due to a suspicious mammogram,
      had received a cancer diagnosis or had received medical follow-up after a breast
      cancer-surgery. Data from the genetic counseling group was also compared to
      normative data. Participants filled in the Hospital Anxiety and Depression Scale
      twice: prior to a potentially stressful event and 14 days after the event.
      RESULTS: Pre-counseling cancer genetic counselees reported significant lower
      level of anxiety compared to the cancer-related group, but higher levels of
      anxiety compared to the general population. Furthermore, the level of depression
      observed within the genetic counseling group was lower compared to other
      participants. Post-event there was no significant difference in anxiety levels
      between the cancer genetic counselees and all other groups; however, the level of
      depression reported in the self-referred group was significantly lower than
      observed in all other groups. Notably, the level of anxiety and depression had
      decreased significantly from pre-to post-events within the genetic counseling
      group. In the cancer-related group only the level of anxiety had decreased
      significantly post-event. CONCLUSION: Individuals who attend cancer genetic
      counseling do not suffer more anxiety or depression compared to all other cancer
      related groups. However, some counselees might need additional sessions and
      extended support. Thus, identifying extremely worried individuals who need more
      support, and allocating further resources to their care, seems to be more
      sufficient.

PMID- 21864050
TI  - Plasma citrulline levels predict intestinal toxicity in patients treated with
      pelvic radiotherapy.
AB  - BACKGROUND: Radiotherapy (RT) for abdominal and pelvic malignancies often causes
      severe small bowel toxicity. Citrulline concentrations are known to decrease with
      intestinal failure. We thus evaluated the feasibility of plasma citrulline levels
      in predicting radiation-induced intestinal toxicity. MATERIAL AND METHODS: Fifty
      three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy
      pelvic RT using conventional fractionation were prospectively evaluated. Patients
      with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma
      citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and
      four months post-RT. Dose-volume histogram, citrulline concentration changes, and
      weekly intestinal toxicity scores were analyzed. RESULTS: Mean age was 63 years
      (range: 43-81 years) and mean baseline citrulline concentration was 38.0 +/- 10.1
      MUmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 +/-
      5.9 MUmol/l; p < 0.0001), treatment end (29.9 +/- 8.8 MUmol/l; p < 0.0001), and
      four months post-treatment (34.3 +/- 12.1; p = 0.01). The following factor pairs
      were significantly positively correlated: Citrulline concentration/mean bowel
      dose during, end of treatment, and four months post-RT; dose-volume
      parameters/citrulline change groups; cumulative mean radiation dose/intestinal
      toxicity at end and four months post-RT; citrulline changes/intestinal toxicity
      during and end of RT. Citrulline concentration changes significantly differed
      during treatment according to RTOG intestinal toxicity grades (p < 0.0001).
      Although the citrulline changes differed significantly within RTOG intestinal
      toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not
      differ significantly at the end of the treatment. At four months after RT, no
      significant differences were apparent. CONCLUSION: Citrulline-based assessment
      scores are objective and should be considered in measuring radiation-induced
      intestinal toxicity.

PMID- 21864051
TI  - Artificial neural network analysis to assess hypernasality in patients treated
      for oral or oropharyngeal cancer.
AB  - OBJECTIVE: Investigation of applicability of neural network feature analysis of
      nasalance in speech to assess hypernasality in speech of patients treated for
      oral or oropharyngeal cancer. PATIENTS AND METHODS: Speech recordings of 51
      patients and of 18 control speakers were evaluated regarding hypernasality,
      articulation, intelligibility, and patient-reported speech outcome. Feature
      analysis of nasalance was performed on /a/, /i/, and /u/ and on the entire
      stretch of speech. RESULTS: Nasalance distinguished significantly between
      patients and controls. Nasalance in /a/ and /i/ predicted best intelligibility,
      nasalance in /a/ predicted best articulation, and nasalance in /i/ and /u/
      predicted best hypernasality. CONCLUSION: Feature analysis of nasalance in oral
      or oropharyngeal cancer patients is feasible; prediction of subjective parameters
      varies between moderate and poor.

PMID- 21864053
TI  - Intramuscular administration of a VEGF zinc finger transcription factor activator
      (VEGF-ZFP-TF) improves functional outcomes in SOD1 rats.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron loss leading
      to paralysis and death. Vascular endothelial growth factor (VEGF) has angiogenic,
      neurotrophic, and neuroprotective properties, and has preserved neuromuscular
      function and protected motor neurons in rats engineered to overexpress the human
      gene coding the mutated G93A form of the superoxide dismutase-1 (SOD1). We
      assessed the effects of intramuscular administration of a plasmid that encodes a
      zinc finger protein transcription factor (ZFP-TF) engineered to induce VEGF
      expression in the SOD1 rat model of ALS. Weekly injections of the plasmid
      preserved ipsilateral hindlimb grip strength and markedly improved rotarod
      performance in SOD1 rats compared to the vehicle-treated group. The number of
      motor neurons and the proportion of innervated neuromuscular junctions were
      similar in both groups. In conclusion, our data suggest that administration of
      the VEGF-ZFP-TF may be neuroprotective and has potential as a safe and practical
      approach for the management of motor disability in ALS.

PMID- 21864054
TI  - The relationship between inflammation, endothelial dysfunction and proteinuria in
      patients with diabetic nephropathy.
AB  - OBJECTIVES: Diabetic nephropathy (DN) is a major manifestation of microangiopathy
      in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors
      in the formation of endothelial dysfunction. Endothelial dysfunction is a major
      contributor to the complications of DM. The aim of the present study was to
      investigate the possible relationship between inflammation, endothelial
      dysfunction and proteinuria in patients with diabetic nephropathy. MATERIALS AND
      METHODS: Plasma TNF-alpha and IL-6, pro-inflammatory cytokines, concentrations
      were measured in 25 patients with DN and in 30 diabetic control subjects. Also,
      we evaluated the markers of endothelial dysfunction such as flow mediated
      dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media
      thickness (CIMT). RESULTS: TNF-alpha, IL-6 and high-sensitivity C-reactive
      protein concentrations were significantly higher (p = 0.012, p = 0.006 and p <
      0.001, respectively) in the patients with DN than the controls. And, urinary
      protein concentrations were significantly higher (p < 0.001) but eGFR levels were
      significantly lower (p < 0.001) in the patients with DN. FMD was significantly
      lower in DN patients (p < 0.001). We have observed that FMD correlated negatively
      with body mass index (r = -0.424, p < 0.05). And there was also a positive
      correlation between TNF-alpha and urinary protein concentrations in the patients
      with DN (p < 0.05). CONCLUSION: TNF-alpha, IL-6, hsCRP and urinary protein
      concentrations are higher in the DN patients. There were no correlations among
      pro-inflammatory cytokines concentrations and markers of vascular endotelial
      disfunction. These findings did not show vascular endothelial dysfunction, but
      may indicate glomerular endothelial dysfunction.

PMID- 21864055
TI  - Alcohol consumption and cancer risk.
AB  - This review focuses on selected aspects of the relation between alcohol
      consumption and cancer risk. Heavy alcohol consumption (i.e., >=4 drinks/day) is
      significantly associated with an increased risk of about 5-fold for oral and
      pharyngeal cancer and esophageal squamous cell carcinoma, 2.5-fold for laryngeal
      cancer, 50% for colorectal and breast cancers, and 30% for pancreatic cancer.
      These estimates are based on a large number of epidemiological studies and are
      generally consistent across strata of several covariates. The evidence suggests
      that at low doses of alcohol consumption (i.e., <=1 drink/day) the risk is also
      increased by about 20% for oral and pharyngeal cancer and 30% for esophageal
      squamous cell carcinoma. Thus, for these sites there is little evidence of a
      threshold effect. While consumption of fewer than 3 alcoholic drinks/wk is not
      associated with an increased risk of breast cancer, an intake of 3 to 6 drinks/wk
      might already yield a (small) increase in risk. On the other hand, intakes up to
      1 drink/day are not associated to the risk of laryngeal, colorectal, and
      pancreatic cancer. The positive association between alcohol consumption and the
      risk of head and neck cancers is independent from tobacco exposure.

PMID- 21864056
TI  - Leadership's impact in turnover and career abandonment intention: the Azorean
      Hospital Nurses Case.
AB  - The authors aimed to identify nurse managers' leadership behaviors and determine
      if they had a direct impact on turnover or career abandonment intention among
      nurses. This descriptive and inferential study was conducted in two public
      hospitals in Azores (Portugal). The sample consisted of 266 individuals (22 head
      nurses and 244 staff nurses). Data were collected during May 2010. The most
      expressive leadership styles were S(2) (persuading) and S(3) (sharing). Nurse
      retention seems easier when dealing with profile S(2)-S(3) or effective
      adaptability. This study brings light to a severe problem of nurse retention in
      Portugal.

PMID- 21864057
TI  - Healthcare financing: how does Turkey compare?
AB  - The authors provide an overview of Turkey's healthcare financing. After comparing
      financing data on Turkey and other Organization for Economic Cooperation and
      Development (OECD) member countries, they examine Turkey's performance on a wide
      range of healthcare input and outcome indicators using descriptive data drawn
      from the World Health Organization, World Bank, OECD, and Turkish Statistical
      Institute. The data analysis shows that Turkey ranks low by a number of key
      healthcare indicators across the OECD countries. Empirical analysis suggests that
      although many factors are associated with improvements in healthcare outcomes, a
      significant part of changes in life expectancy at birth are associated with
      higher spending on healthcare.

PMID- 21864058
TI  - Hospitals for sale.
AB  - The pace of hospital merger and acquisition activity reflects the economic theory
      of supply and demand: Publicly traded hospital companies, private equity funds,
      and large nonprofit hospital systems are investing capital to purchase and
      operate freestanding community hospitals at a time when many of those hospitals
      find themselves short of capital reserves and certain forms of management
      expertise. But the sale of those community hospitals also raises questions about
      the impact of absentee ownership on the communities which those hospitals serve.

PMID- 21864059
TI  - The CpG island methylation regulated expression of endothelial proangiogenic
      genes in response to beta-carotene and arachidonic acid.
AB  - beta-carotene (BC) and arachidonic acid (AA) were demonstrated to modulate
      carcinogenesis by influencing angiogenesis. DNA methylation is an epigenetic
      mechanism regulating gene expression. The aim of this study was to investigate
      whether BC and AA change DNA methylation and expression of the proangiogenic
      genes, which might help explain their impact on carcinogenesis. Human umbilical
      vein endothelial cells (HUVECs) and endothelial progenitors (EPCs) were incubated
      with BC or AA for 24 h. Based on microarray results, we selected 18 genes for DNA
      methylation analysis. CpG island methylation was quantified using the combined
      bisulphite restriction analysis method and methylation sensitive restriction
      enzymes. Relative gene expression was quantified using a quantitative real-time
      PCR (qRT-PCR) method. Incubation with AA significantly decreased methylation of
      the promoters of both KDR (P = 0.048) and Notch4 (P = 0.027) genes in HUVECs. In
      EPCs, BC increased methylation of the connexin 43 gene (P = 0.036). qRT-PCR
      showed that AA (P = 0.059) and BC (P = 0.044) upregulated the KDR gene expression
      in HUVECs. Connexin 43 gene expression was induced in the presence of 1 MUM (P =
      0.039) and 3 MUM (P = 0.043) BC in EPCs. No significant changes in the Notch4
      gene expression were found. The impact of BC and AA on carcinogenesis may be due,
      at least in part, to changes in expression of angiogenic genes and these
      transcriptional effects may be mediated by changes in methylation of CpG islands
      in the gene promoters. However more research is necessary to confirm this
      hypothesis.

PMID- 21864060
TI  - A genome-wide microarray highlights the antiinflammatory genes targeted by oolong
      tea theasinensin A in macrophages.
AB  - Theasinensin A is one of the oolong tea theasinensins, which differ from green
      tea catechins and black tea theaflavins. In a previous study, we found that
      theasinesin A had a potential effect on antiinflammation since theasinensin A
      suppressed LPS-induced COX2 and PGE(2) production. To clarify the molecular
      mechanisms, we investigated the gene expression profiling in macrophage-like
      cells treated with theasinensin A through a genome-wide DNA microarray in the
      present study. Among 22,050 oligonucleotides, the expression levels of 406 genes
      were increased by >=3-fold in LPS-activated RAW264 cells, 259 gene signals of
      which were attenuated by theasinensin A treatment (>=2-fold). Expression levels
      of 717 genes were decreased by >=3-fold in LPS-activated cells, of which 471 gene
      signals were restored by theasinensin A treatment (>=2-fold). These genes were
      further categorized as "defense, inflammatory response, cytokines activities, and
      receptor activities," and some of them were confirmed by real-time polymerase
      chain reaction. Furthermore, pathways analysis revealed that theasinensin A
      regulated the relevant expression networks of chemokines, interleukins, and
      interferons to exert its antiinflammatory effects.

PMID- 21864061
TI  - Gene expression patterns in livers of Hispanic patients infected with hepatitis C
      virus.
AB  - We report a gene expression study aimed at the identification of genes
      differentially expressed in the livers of Hispanic patients infected with
      hepatitis C virus (HCV). Six uninfected controls were compared with 14 HCV(+)
      patients in which the liver biopsies were obtained at the time of diagnosis.
      Among the latter, five patients were also analyzed 4 weeks after the onset of
      standard anti-HCV therapy (pegylated interferon-alpha + ribavirin). We identified
      many genes up- or down-regulated by the infection with HCV in the human livers.
      When these genes were subjected to pathway analysis, several prominent pathways
      were revealed including many interferon (IFN)-inducible pathways as well as
      immune cell trafficking, inflammation, anti-microbial responses, and even cancer.
      We detected expression of many genes that have previously been associated with
      HCV infection, as well as several novel genes including CD47. The genes induced
      by HCV infection showed large expression changes, whereas the genes induced by
      the IFN-alpha combination therapy were relatively few (including MX2, ORMDL3,
      GPAM, KOPX18, TMEM56, and HBP1) and they reflected relatively small expression
      changes. This is the first study to identify changes in gene expression in livers
      of HCV(+) Hispanic patients and the first to identify genes induced by anti-HCV
      combination therapy in the human liver.

PMID- 21864062
TI  - Systemic lupus erythematosus in Hispanics.
AB  - Systemic lupus erythematosus is a serious autoimmune disease that causes
      significant morbidity and mortality. It is also a disease for which several
      clinical differences among ethnic groups have been documented. Until recently,
      Hispanics, as separate patient cohort, had not been included in these studies. As
      a result, there is currently little information concerning its characteristics
      both at the clinical and at the molecular levels. With the currently available
      data, we can ascertain that this population exhibits considerable heterogeneity,
      in which some genetic mutations have been detected that may confer greater
      susceptibility and/or protection against the disease. The important differences
      in the clinical manifestations include a higher rate of renal complications as
      well as greater mortality. The latter may be due, at least in part, to lower
      socio-economic levels and inappropriate access to health care. However, given the
      limited data available that have focused on potential molecular mechanisms that
      may affect the Hispanic population affected with lupus, we cannot conclude that
      all the differences in disease outcome, complications, and severity that affect
      this patient population may be due to sociological factors. We conclude that more
      research is required to evaluate potential genetic and molecular factors that
      affect Hispanic lupus patients.

PMID- 21864063
TI  - The impact of genetic variability on liver disease in the Hispanic/Latin-American
      population.
AB  - Liver cirrhosis is within the top 10 causes of death in Latin-American countries
      and recent evidence suggests that Hispanics in the USA have a more aggressive
      course of many types of liver disease and show lower response to treatment of
      hepatitis C compared with other ethnic groups. Although environmental factors are
      very important, they do not appear to fully account for the observed ethnic
      differences in the incidence of cirrhosis and progression rates. Genome-wide
      association studies have been a powerful tool to identify genetic variants that
      directly confer susceptibility to liver disease. Here, we review the current
      knowledge on genetic variants associated with the most common types of liver
      disease that may contribute to ancestry-related differences in disease
      progression and mortality.

PMID- 21864064
TI  - Vitamin D: a link between Epstein-Barr virus and multiple sclerosis development?

PMID- 21864066
TI  - Pramipexole extended release in Parkinson's disease.
AB  - Pramipexole extended release (ER) is a new once-daily formulation of pramipexole,
      a nonergot dopamine agonist, which is available in five dosage strengths: 0.26
      (0.375) mg, 0.52 (0.75) mg, 1.05 (1.5) mg, 2.1 (3) mg and 3.15 (4.5) mg (all
      doses are expressed in terms of pramipexole base and the corresponding dose
      strengths of pramipexole salt are given in brackets). Pramipexole ER is currently
      approved as monotherapy in early Parkinson's disease (PD), as well as an adjunct
      therapy to levodopa in advanced PD. Compared with the immediate release (IR)
      formulation, the ER formulation offers several advantages, including the
      potential for improved compliance owing to its simple once-daily dosing regimen
      and steadier plasma levels over 24 h. Double-blind, randomized, placebo and
      active comparator controlled trials in early, as well as advanced PD, established
      the superiority of both pramipexole ER and IR over placebo. The overnight switch
      from pramipexole IR three times a day to ER once-daily in early PD has been shown
      to be successful in more than 80% of patients. Pramipexole ER is well tolerated,
      with a similar adverse event profile to pramipexole IR. The aim of this article
      is to provide a short review of the most relevant pharmacological and clinical
      data on pramipexole ER.

PMID- 21864067
TI  - Brain 11: what's new in stroke research?
AB  - The International Society for Cerebral Blood Flow and Metabolism promotes
      research centered on furthering the understanding of neurological conditions that
      result from ischemia and related injuries. This previous meeting (Brain 11)
      focused on state-of-the-art research, which shed light on the pathophysiology of
      these conditions as they pertained to the cerebral vasculature - including the
      BBB - and angiogenesis, immune mechanisms, regeneration and repair following such
      insults. The meeting also covered a variety of potential therapeutic strategies
      ranging from cell-based therapy, induced tolerance and the targeting of specific
      immune or cell death pathways. In addition, there was a focus on how the
      peripheral circulation contributes to such types of brain injury.

PMID- 21864068
TI  - Movement disorders in focus: experts debate on pathophysiology and concomitant
      signs.
AB  - The Movement Disorders Society (MDS) organized its 15th International Annual
      Congress of Parkinson's Disease and Movement Disorders in Toronto (Canada), on 5
      9 June 2011. This year's theme was 'Behavioral and motor interfaces of movement
      disorders, from laboratory to patient care'. The congress was organized following
      a routine that has been well established through years of experience: with the
      exception of the first day, each day of the congress consisted of 3-h plenary
      sessions followed by parallel sessions, teaching courses, video sessions and
      skills workshops, fulfilling the educational purpose of the congress.

PMID- 21864069
TI  - Is there a future for donepezil therapy in the treatment of multiple sclerosis
      related cognitive impairment?
AB  - Multicenter randomized clinical trial of donepezil for memory impairment in
      multiple sclerosis. Neurology 76(17), 1500-1507 (2011). Cognitive impairment is a
      core feature of multiple sclerosis (MS), is detectable in up to 65% of patients
      and represents the most important predictor of the subject's work and vocational
      status. The cognitive domains most frequently involved are attention, information
      processing speed, episodic memory and executive functions. To date, there is no
      approved drug or evidence-based strategy for the treatment of this disabling
      condition. Promising findings were provided in a monocentric randomized trial on
      donepezil - a reversible inhibitor of acetylcholinesterase - for the treatment of
      MS-related memory impairment. However, a larger multicentric trial failed to
      confirm any efficacy of donepezil on memory impairment in MS subjects. Possible
      implications of these findings are discussed in this article.

PMID- 21864070
TI  - What happens when natalizumab therapy is stopped?
AB  - Natalizumab is an alpha-4 integrin antagonist used for the treatment of relapsing
      multiple sclerosis (MS). Concerns with the drug have a risen owing to a
      heightened risk of progressive multifocal leukoencephalopathy, which has caused
      some physicians to interrupt or stop treatment altogether. The article under
      review evaluates the safety of natalizumab treatment interruption, including the
      rate and magnitude of the return of MS disease activity toward baseline levels by
      clinical and MRI measures. The investigators found that by 4-7 months after
      natalizumab treatment interruption, MS disease activity began to reach baseline
      levels, which is consistent with the known elimination kinetics of natalizumab.
      The duration of prior natalizumab exposure or alternate MS treatments during
      interruption was demonstrated to not affect return of disease activity. Despite
      nearly similar disease activity after natalizumab treatment, patients with highly
      active disease prior to treatment had a return of disease activity that was
      greater in magnitude when compared with those with less active disease. Most
      significantly, the study did not show evidence of rebound following natalizumab
      cessation. We agree with these conclusions, but note that a subgroup of MS
      patients may demonstrate highly active disease after natalizumab cessation.

PMID- 21864071
TI  - Lacunar infarct and cognitive decline.
AB  - Lacunar infarcts or lacunes result from occlusion of a single penetrating artery
      and account for approximately a quarter of cerebral infarctions. The short-term
      prognosis of symptomatic lacunar infarct is favorable - that is, low early
      mortality and a high proportion of symptom-free patients at hospital discharge -
      but the prognosis in the mid- and long-term is less favorable as there is an
      increased risk of death, recurrence of stroke and vascular-type dementia. This
      unfavorable prognosis is mostly related to asymptomatic progression of small
      vessel disease. Therefore, the consideration of lacunar infarct as a relatively
      benign disorder is misleading. Whereas the clinical relevance of lacunar infarct
      to lacunar syndromes is widely accepted, the degree to which lacunes affect
      cognitive function remains unclear. The reviewed article presents new data from
      the multinational Leukoaraiosis and Disability (LADIS) study, which shows that an
      increase in silent lacunes parallels significantly with longitudinal cognitive
      decline in executive functions and psychomotor speed. The study is discussed in
      the context of the current state and knowledge regarding cognitive impairment in
      ischemic cerebral small-vessel disease, in particular regarding its health
      consequences.

PMID- 21864072
TI  - Cluster headache and the hypothalamus: causal relationship or epiphenomenon?
AB  - Typical clinical features of cluster headache (CH) include circadian/circannual
      rhythmicity and ipisilateral cranial autonomic features. This presentation has
      led to the assumption that the hypothalamus plays a pivotal role in this primary
      headache disorder. Several studies using neuroimaging techniques or measuring
      hormone levels supported the hypothesis of a hypothalamic involvement in the
      underlying pathophysiology of CH. Animal studies added further evidence to this
      hypothesis. Based on previous data, even invasive treatment methods, such as
      hypothalamic deep brain stimulation, are used for therapy. However, the principal
      question of whether these alterations are pathognomonic for CH or whether they
      might be detected in trigeminal pain disorders in general, in terms of an
      epiphenomenon, is still unsolved. This article summarizes studies on hypothalamic
      involvement in CH pathophysiology, demonstrates the involvement of the
      hypothalamus in other diseases and tries to illuminate the role of the
      hypothalamus based on this synopsis.

PMID- 21864073
TI  - Reversible cerebral vasoconstriction syndrome: current and future perspectives.
AB  - Reversible cerebral vasoconstriction syndromes (RCVS) are characterized by
      recurrent acute severe headaches, namely thunderclap headaches, and multifocal
      segmental vasoconstrictions. Interest has arisen in the definitions, clinical
      presentations, differential diagnoses, risk factors and complications of RCVS.
      This article will comprehensively review the milestone monographs and the latest
      research work addressing these issues. Studies that have focused on the
      relationship between RCVS and thunderclap headache will be detailed. We will also
      discuss research on the enigmatic pathophysiology and potential therapeutic
      approaches. Up-to-date information and challenges, undergoing studies and future
      research directions will be deeply probed.

PMID- 21864074
TI  - Chronic cerebrospinal venous insufficiency in multiple sclerosis: diagnostic,
      pathogenetic, clinical and treatment perspectives.
AB  - Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in
      multiple sclerosis patients. CCSVI is characterized by impaired brain venous
      drainage due to outflow obstruction in the extracranial venous system, mostly
      related to anomalies in the internal jugular and azygos veins. The current CCSVI
      diagnosis is based on Doppler sonography of extracranial and transcranial venous
      hemodynamics criteria. To date, prevalence estimates of CCSVI, provided by
      different groups using various imaging methods of assessment, vary widely from
      none to 100%. There is an urgent need to define and validate the spectrum of
      cranial/extracranial venous anomalies and to establish reliable, diagnostic gold
      standard test(s). The potential usefulness of endovascular treatment for CCSVI in
      multiple sclerosis patients is still unknown.

PMID- 21864076
TI  - Antiganglioside antibodies in Guillain-Barre syndrome and its related conditions.
AB  - Guillain-Barre syndrome (GBS) is typically classified into two major subtypes:
      acute inflammatory demyelinating neuropathy and acute motor axonal neuropathy.
      Its most recognizable variant is Fisher syndrome. The last two decades have seen
      considerable advances in our understanding of GBS. Of note, various
      autoantibodies against ganglioside antigens have been identified and found to
      have significant associations with the axonal forms of GBS and Fisher syndrome.
      In this article, we discuss the different clinical presentations in GBS and the
      role of antiganglioside antibodies in their underlying pathogenesis. We also
      discuss the impact that antiganglioside antibodies have had in the development of
      experimental models and treatment modalities in GBS.

PMID- 21864075
TI  - Harnessing the therapeutic potential of mesenchymal stem cells in multiple
      sclerosis.
AB  - Phase I clinical trials exploring the use of autologous mesenchymal stem cell
      (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number
      of centers across the world. MS is a complex and chronic immune-mediated and
      neurodegenerative disease influenced by genetic susceptibility and environmental
      risk factors. The ideal treatment for MS would involve both attenuation of
      detrimental inflammatory responses, and induction of a degree of tissue
      protection/regeneration within the CNS. Preclinical studies have demonstrated
      that both human-derived and murine-derived MSCs are able to improve outcomes in
      the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs
      ameliorate experimental autoimmune encephalomyelitis is being intensely
      investigated. One of the major mechanisms of action of MSC therapy is to inhibit
      various components of the immune system that contribute to tissue destruction.
      Emerging evidence now supports the idea that MSCs can access the CNS where they
      can provide protection against tissue damage, and may facilitate tissue
      regeneration through the production of growth factors. The prospect of cell-based
      therapy using MSCs has several advantages, including the relative ease with which
      they can be extracted from autologous bone marrow or adipose tissue and expanded
      in vitro to reach the purity and numbers required for transplantation, and the
      fact that MSC therapy has already been used in other human disease settings, such
      as graft-versus-host and cardiac disease, with initial reports indicating a good
      safety profile. This article will focus on the theoretical and practical issues
      relevant to considerations of MSC therapy in the context of MS.

PMID- 21864077
TI  - Traumatic white matter injury and toxic leukoencephalopathies.
AB  - White matter injury may be secondary to a range of neurodegenerative disorders,
      such as the common dementing disorders of the elderly, or may be a consequence of
      specific white matter disorders, such as multiple sclerosis and the rare
      leukodystrophies. This article will focus on two relatively common primary groups
      of disorders of the white matter, traumatic white matter injury and toxic
      leukoencephalopathies. Traumatic axonal injury may be focal or diffuse, and is
      associated with a clinical spectrum ranging from concussion through to coma and
      death. The molecular mechanisms underlying axonal degeneration secondary to
      traumatic axonal degeneration are being elucidated and may give an insight into
      potential therapeutic targets. Toxic leukoencephalopathy may be secondary to
      exposure to a wide range of compounds, including chemotherapeutic drugs. These
      toxins may produce white matter injury through a range of mechanisms, and the
      potential toxic effects of compounds need to be considered when assessing a
      patient with a nonspecific leukoencephalopathy.

PMID- 21864078
TI  - Cell replacement therapy for Parkinson's disease: how close are we to the clinic?
AB  - Cell replacement therapy (CRT) offers great promise as the future of regenerative
      medicine in Parkinson's disease (PD). Three decades of experiments have
      accumulated a wealth of knowledge regarding the replacement of dying neurons by
      new and healthy dopaminergic neurons transplanted into the brains of animal
      models and affected patients. The first clinical trials provided the proof of
      principle for CRT in PD. In these experiments, intrastriatal transplantation of
      human embryonic mesencephalic tissue reinnervated the striatum, restored dopamine
      levels and showed motor improvements. Sequential controlled studies highlighted
      several problems that should be addressed prior to the wide application of CRT
      for PD patients. Moreover, owing to ethical and practical problems, embryonic
      stem cells require replacement by better-suited stem cells. Several obstacles
      remain to be surpassed, including identifying the best source of stem cells for
      A9 dopaminergic neuron generation, eliminating the risk of tumor formation and
      the development of graft-induced dyskinesias, and standardizing dopaminergic cell
      production in order to enable clinical application. In this article, we present
      an update on CRT for PD, reviewing the research milestones, various stem cells
      used and tailored differentiation methods, and analyze the information gained
      from the clinical trials.

PMID- 21864080
TI  - Prodomains regulate the synthesis, extracellular localisation and activity of TGF
      beta superfamily ligands.
AB  - All transforming growth factor-beta (TGF-beta) ligands are synthesised as
      precursor molecules consisting of a signal peptide, an N-terminal prodomain and a
      C-terminal mature domain. During synthesis, prodomains interact non-covalently
      with mature domains, maintaining the molecules in a conformation competent for
      dimerisation. Dimeric precursors are cleaved by proprotein convertases, and TGF
      beta ligands are secreted from the cell non-covalently associated with their
      prodomains. Extracellularly, prodomains localise TGF-beta ligands within the
      vicinity of their target cells via interactions with extracellular matrix
      proteins, including fibrillin and perlecan. For some family members (TGF-beta1,
      TGF-beta2, TGF-beta3, myostatin, GDF-11 and BMP-10), prodomains bind with high
      enough affinity to suppress biological activity. The subsequent mechanism of
      activation of these latent TGF-beta ligands varies according to cell type and
      context, but all activating mechanisms directly target prodomains. Thus,
      prodomains control many aspects of TGF-beta superfamily biology, and alterations
      in prodomain function are often associated with disease.

PMID- 21864081
TI  - Similarity in dental maturation in two ethnic groups of London children.
AB  - BACKGROUND: The existence of ethnic differences in dental maturity is uncertain.
      AIMS: The aims were to assess the impact of ethnic group and sex on tooth
      formation and report two new dental age estimation methods. SUBJECTS AND METHODS:
      The sample was radiographs of White and Bangladeshi dental patients in London,
      England (529 males, 521 females) of 2-22 years. Mandibular permanent teeth were
      staged after Moorrees et al. (1963, J Dent Res 42:1490). Average age entering
      tooth stages was calculated using logistic regression with ethnic group and sex
      as explanatory factors. Maturity data were adapted for age prediction (N25a) and
      mean age within stage (N25b) was calculated. RESULTS: Mean ages between ethnic
      groups was not significantly different in 83 of 91 individual tooth stage
      comparisons in males and 77 of 91 comparisons in females. Variation within each
      group was greater than variation between groups. For the combined ethnic group
      comparison of males and females, results show that average age of most canine and
      premolar root stages in females was significantly earlier than males and third
      molar root formation was later in females compared to males (p < 0.05).
      CONCLUSION: Dental maturity of permanent teeth was similar in these ethnic
      groups.

PMID- 21864082
TI  - Impact of sickle cell trait on physical growth in tribal children of Mandla
      district in Madhya Pradesh, India.
AB  - BACKGROUND: Reliable reports on growth impairment in sickle cell trait (SCT)
      children in India are lacking despite contradictory findings reported earlier.
      AIM: The present study assessed the impact of SCT on physical growth of tribal
      children of Mandla district. SUBJECTS AND METHODS: Weight, height,
      circumferences, breadths, lengths and skinfolds were recorded on 6190 children,
      inclusive of 732 SCT children, from birth to 12 years of age using a cross
      sectional design. The sickle test was conducted in the field using 2% sodium
      metabisulphite followed by electrophoresis. RESULTS: No significant difference in
      mean values was observed in the majority of the age groups between SCT and normal
      children for all 11 body measurements. However, inconsistent growth patterns in
      these measurements among SCT children were evident. Body weight was more
      deficient than height or other body measurements in the children when compared to
      Indian and National Centre for Health Statistics (NCHS) standards, while
      bicristal breadth was comparable with Indian standards. CONCLUSIONS: There was no
      significant impact of SCT observed on growth of children irrespective of sex.
      Notably, growth of SCT girls was comparable to their normal counterparts. The
      actual growth difference between normal and SCT children may have been masked on
      account of poor attainment of annual gain in each successive age group.

PMID- 21864083
TI  - Llama antibody fragments have good potential for application as HIV type 1
      topical microbicides.
AB  - There is an urgent global need for preventive strategies against HIV-1
      infections. Llama heavy-chain antibody fragments (VHH) are a class of molecules
      recently described as potent cross-clade HIV-1 entry inhibitors. We studied the
      potential of a VHH-based microbicide in an application-oriented fashion. We show
      that VHH can be inexpensively produced in high amounts in the GRAS organism
      Saccharomyces cerevisiae, resulting in a very pure and endotoxin free product.
      VHH are very stable under conditions they might encounter during transport,
      storage, or use by women. We developed active formulations of VHH in aqueous gel
      and compressed and lyophilized tablets for controlled release from an
      intravaginal device. The release profile of the VHH from, e.g., a vaginal ring
      suggests sufficient bioavailability and protective concentration of the molecule
      at the mucosal site at the moment of the infection. The ex vivo penetration
      kinetics through human tissues show that the VHH diffuse into the mucosal layer
      and open the possibility to create a second defense layer either by blocking the
      HIV receptor binding sites or by blocking the receptors of immune cells in the
      mucosa. In conclusion, our data show that VHH have a high potential for HIV-1
      microbicide application because of their low production costs, their high
      stability, and their favorable release and tissue penetration properties.

PMID- 21864084
TI  - Whole-genome QTL analysis of Stagonospora nodorum blotch resistance and
      validation of the SnTox4-Snn4 interaction in hexaploid wheat.
AB  - Necrotrophic effectors (also known as host-selective toxins) are important
      determinants of disease in the wheat-Stagonospora nodorum pathosystem. To date,
      five necrotrophic effector-host gene interactions have been identified in this
      system. Most of these interactions have additive effects while some are
      epistatic. The Snn4-SnTox4 interaction was originally identified in a recombinant
      inbred population derived from a cross between the Swiss winter wheat cultivars
      'Arina' and 'Forno' using the S. nodorum isolate Sn99CH 1A7a. Here, we used a
      recombinant-inbred population consisting of 121 lines developed from a cross
      between the hexaploid land race Salamouni and the hexaploid wheat 'Katepwa' (SK
      population). The SK population was used for the construction of linkage maps and
      quantitative trait loci (QTL) detection using the Swiss S. nodorum isolate Sn99CH
      1A7a. The linkage maps developed in the SK population spanned 3,228 centimorgans
      (cM) and consisted of 441 simple-sequence repeats, 9 restriction fragment length
      polymorphisms, 29 expressed sequence tag sequence-tagged site markers, and 5
      phenotypic markers. The average marker density was 6.7 cM/marker. Two QTL,
      designated QSnb.fcu-1A and QSnb.fcu-7A on chromosome arms 1AS and 7AS,
      respectively, were associated with disease caused by the S. nodorum isolate
      Sn99CH 1A7a. The effects of QSnb.fcu-1A were determined by the Snn4-SnTox4
      interaction and accounted for 23.5% of the phenotypic variation in this
      population, whereas QSnb.fcu-7A accounted for 16.4% of the phenotypic variation
      for disease but was not associated with any known effector sensitivity locus. The
      effects of both QTL were largely additive and collectively accounted for 35.7% of
      the total phenotypic variation. The results of this research validate the effects
      of a compatible Snn4-SnTox4 interaction in a different genetic background, and it
      provides knowledge regarding genomic regions and molecular markers that can be
      used to improve Stagonospora nodorum blotch resistance in wheat germplasm.

PMID- 21864085
TI  - Estimation of leaf wetness duration requirements of foliar fungal pathogens with
      uncertain data-an application to Mycosphaerella nawae.
AB  - Wetness of the host surface is a critical environmental factor for the
      development of foliar fungal diseases, but it is difficult to estimate the
      wetness durations required by pathogens for infection when only few experimental
      data are available. In this paper, we propose a method to estimate wetness
      duration requirements of foliar fungal pathogens when precise experimental data
      are not available. The proposed method is based on approximate Bayesian
      computation. It only requires lower and upper bounds of wetness duration
      requirements for one or fewer temperatures. We describe the method, show how to
      apply it to an infection model, and then present a case study on Mycosphaerella
      nawae, the causal agent of circular leaf spot of persimmon. In this example, the
      parameters of a simple infection model were estimated using experimental data
      found in the literature for the pathogen, and the model was applied to assess the
      risk in a Spanish area recently affected by the disease. The results showed that
      the probability of successful infection was higher than 0.5 for 32% of the on
      site wetness durations recorded in the affected area. Results obtained with
      simulated data showed that our method was able to improve the estimation of
      wetness duration requirement. Given the flexibility of the proposed method, we
      expect it to become adopted for assessing the risk of introduction of exotic
      fungal plant pathogens.

PMID- 21864086
TI  - Effect of temperature on cortical infection by Plasmodiophora brassicae and
      clubroot severity.
AB  - A study was conducted to assess the effect of temperature on infection and
      development of Plasmodiophora brassicae in the root cortex of Shanghai pak choy
      (Brassica rapa subsp. chinensis) and on subsequent clubroot severity. Ten-day-old
      seedlings were grown individually, inoculated with resting spores, and maintained
      in growth cabinets at 10, 15, 20, 25, and 30?C. Seedlings were harvested at 2-day
      intervals, starting 8 days after inoculation (DAI) and continuing until 42 DAI.
      Roots were assessed at 4-day intervals for the incidence of cortical infection
      and stage of infection (young plasmodia, mature plasmodia, and resting spores),
      at 2-day intervals for symptom development and clubroot severity, and at 8-day
      intervals for the number of spores per gram of gall. Temperature affected every
      stage of clubroot development. Cortical infection was highest and symptoms were
      observed earliest at 25?C, intermediate at 20 and 30?C, and lowest and latest at
      15?C. No cortical infection or symptoms were observed at 42 DAI in plants grown
      at 10?C. A substantial delay in the development of the pathogen was observed at
      15?C. Resting spores were first observed at 38 DAI in plants at 15?C, 26 DAI at
      20 and 30?C, and 22 DAI at 25?C. The yield of resting spores from galls was
      higher in galls that developed at 20 to 30?C than those that developed at 15?C
      over 42 days of assessment. These results support the observation in companion
      studies that cool temperatures result in slower development of clubroot symptoms
      in brassica crops, and demonstrate that the temperature has a consistent pattern
      of effect throughout the life cycle of the pathogen.

PMID- 21864087
TI  - Xylella fastidiosa plasmid-encoded PemK toxin is an endoribonuclease.
AB  - Stable inheritance of pXF-RIV11 in Xylella fastidiosa is conferred by the
      pemI/pemK toxin-antitoxin (TA) system. PemK toxin inhibits bacterial growth; PemI
      is the corresponding antitoxin that blocks activity of PemK by direct binding.
      PemK and PemI were overexpressed in Escherichia coli and activities of each were
      assessed. Purified PemK toxin specifically degraded single-stranded RNA but not
      double-stranded RNA, double-stranded DNA, or single-stranded DNA. Addition of
      PemI antitoxin inhibited nuclease activity of PemK toxin. Purified complexes of
      PemI bound to PemK exhibited minimal nuclease activity; removal of PemI antitoxin
      from the complex restored nuclease activity of PemK toxin. Sequencing of 5' rapid
      amplification of cDNA ends products of RNA targets digested with PemK revealed a
      preference for cleavage between U and A residues of the sequence UACU and UACG.
      Nine single amino-acid substitution mutants of PemK toxin were constructed and
      evaluated for growth inhibition, ribonuclease activity, and PemI binding. Three
      PemK point-substitution mutants (R3A, G16E, and D79V) that lacked nuclease
      activity did not inhibit growth. All nine PemK mutants retained the ability to
      bind PemI. Collectively, the results indicate that the mechanism of stable
      inheritance conferred by pXF-RIV11 pemI/pemK is similar to that of the R100
      pemI/pemK TA system of E. coli.

PMID- 21864088
TI  - Comments regarding the binary power law for heterogeneity of disease incidence.
AB  - The binary power law (BPL) has been successfully used to characterize
      heterogeneity (overdispersion or small-scale aggregation) of disease incidence
      for many plant pathosystems. With the BPL, the log of the observed variance is a
      linear function of the log of the theoretical variance for a binomial
      distribution over the range of incidence values, and the estimated scale (?) and
      slope (b) parameters provide information on the characteristics of aggregation.
      When b = 1, the interpretation is that the degree of aggregation remains constant
      over the range of incidence values observed; otherwise, aggregation is variable.
      In two articles published in this journal in 2009, Gosme and Lucas used their
      stochastic simulation model, Cascade, to show a multiphasic (split-line)
      relationship of the variances, with straight-line (linear) relationships on a log
      log scale within each phase. In particular, they showed a strong break point in
      the lines at very low incidence, with b considerably >1 in the first line segment
      (corresponding to a range of incidence values usually not observed in the field),
      and b being ?1 in the next segment (corresponding to the range of incidence
      values usually observed). We evaluated their findings by utilizing a general
      spatially explicit stochastic simulator developed by Xu and Ridout in 1998, with
      a wide range of median dispersal distances for the contact distribution and
      number of plants in the sampling units (quadrats), and through an assessment of
      published BPL results. The simulation results showed that the split-line
      phenomenon can occur, with a break point at incidence values of ?0.01; however,
      the split is most obvious for short median dispersal distances and large quadrat
      sizes. However, values of b in the second phase were almost always >1, and only
      approached 1 with extremely short median dispersal distances and small quadrat
      sizes. An appraisal of published results showed no evidence of multiple phases
      (although the minimum incidence may generally be too high to observe the break),
      and estimates of b were almost always >1. Thus, it appears that the results from
      the Cascade simulation model represent a special epidemiological case,
      corresponding primarily to a roughly nearest-neighbor population-dynamic process.
      Implications of a multiphasic BPL property may be important and are discussed.

PMID- 21864089
TI  - Gnetum africanum: a wild food plant from the African forest with many nutritional
      and medicinal properties.
AB  - Gnetum africanum is a forest liana that grows abundantly in Central Africa, South
      America, and tropical and subtropical Asia. Its leaves are eaten as a vegetable,
      either raw or finely chopped and cooked; they are also widely used as an
      ingredient in soups and stews and are much in demand for their nutritional and
      therapeutic properties. In the latter application, various fractions of G.
      africanum are used medicinally to treat many different illnesses. Many studies
      have also shown that the chemical composition of the leaves of this plant gives
      it significant nutritional properties, and its high fiber, protein, and calorie
      content support these claims. Several molecular compounds related to the families
      of stilbenes, glycosylflavones, and flavonostilbenes have been isolated and
      identified in the leaf extract of this plant. These molecules give the plant its
      interesting properties and biological activities.

PMID- 21864090
TI  - Bioactive chemicals from carrot (Daucus carota) juice extracts for the treatment
      of leukemia.
AB  - Overwhelming evidence indicates that consumption of fruits and vegetables with
      antioxidant properties correlates with reduced risk for cancers, including
      leukemia. Carrots contain beneficial agents, such as beta-carotene and
      polyacetylenes, which could be effective in the treatment of leukemia. This study
      investigated the effect of carrot juice extracts on myeloid and lymphoid leukemia
      cell lines together with normal hematopoietic stem cells. Leukemia cell lines and
      nontumor control cells were treated with carrot juice extracts for up to 72 hours
      in vitro. Induction of apoptosis was investigated by using annexin V/propidium
      iodide staining followed by flow cytometric analysis, and results were confirmed
      by using 4'-6-diamidino-2-phenylindole morphology. Effects on cellular
      proliferation were investigated via cell cycle analysis and cell counts.
      Treatment of leukemia cell lines with carrot juice extract induced apoptosis and
      inhibited progression through the cell cycle. Lymphoid cell lines were affected
      to a greater extent than were myeloid cell lines, and normal hematopoietic stem
      cells were less sensitive than most cell lines. This study has shown that
      extracts from carrots can induce apoptosis and cause cell cycle arrest in
      leukemia cell lines. The findings suggest that carrots may be an excellent source
      of bioactive chemicals for the treatment of leukemia.

PMID- 21864091
TI  - Fatty acid profiles of four wild mushrooms and their potential benefits for
      hypertension treatment.
AB  - Mushrooms are useful in balancing human diet and treating different health
      problems. The main determinant of the fluidity of erythrocyte membranes and
      rheologic properties of blood is the lipid composition of the membrane, which
      directly depends on lipids present in the diet. Lipid profiles of 4 European wild
      edible mushrooms, as well as the ability of mushroom lipids to modify the
      fluidity of erythrocyte membrane, were examined by using gas chromatography-mass
      spectometry, gas chromatography-flame ionization detector, and electron
      paramagnetic resonance spin probing technique. Lipids from 2 species-
      Macrolepiota procera and Collybia platyphylla--provoked an increase in
      erythrocyte membrane fluidity. Therefore, introduction of these and other wild
      mushrooms with similar lipid profiles to the human diet could be very beneficial
      in the treatment of hypertension and other cardiovascular diseases related to
      decreased fluidity of erythrocyte membranes.

PMID- 21864096
TI  - Evaluation of in vitro percutaneous absorption of olanzapine and fluoxetine HCl:
      enhancement properties of olanzapine.
AB  - The diffusion characteristics of fluoxetine HCl (FLX HCl) and olanzapine (OLZ)
      alone and in combination with each other were studied to determine their in vitro
      permeation behavior across a series of gelling agents through a cellulose
      membrane and human cadaver skin. Klucel 0.5% was selected as the optimal
      formulation to study their diffusion through human cadaver skin. The release
      profiles of drugs acting alone and in combinations were identical in the case of
      the cellulose membrane. However, with human cadaver skin, the permeation of FLX
      HCl in combination with OLZ drastically increased (732 ug) compared with the
      release of FLX HCl alone (43.7 ug), while the release of OLZ remained the same
      whether alone or in combination with FLX HCl (183.7 ug). The results indicate
      that OLZ enhances the diffusion of FLX HCl through the cadaver skin. Follow-up
      studies with OLZ were conducted to further investigate this phenomenon and have
      shown that OLZ enhancement properties are skin reversible as well as
      concentration dependent. Also, a variety of experiments with different
      hydrophilic and lipophilic molecules were conducted, and it was found that OLZ
      enhances the permeation of hydrophilic compounds, while it has no influence on
      lipophilic compounds. Finally, a number of compounds structurally related to OLZ
      were investigated as enhancers, and it was determined that piperazine ring
      attached to the tricyclic system of OLZ is essential for enhancement of FLX HCl
      (1,837 ug).

PMID- 21864097
TI  - Work-related stress and asthma: results from a workforce survey in New Zealand.
AB  - OBJECTIVE: We assessed the association between work-related stress and asthma in
      a cross-sectional workforce survey in New Zealand. METHODS: Men and women
      randomly selected from the Electoral Roll were invited to take part in a
      telephonic interview, which collected information on current workplace exposures
      and respiratory symptoms. Participants rated how stressful they found their
      current job on a five-point scale. We conducted unconditional logistic regression
      to calculate prevalence odds ratios (OR) and 95% confidence intervals (CI) for
      job stress and both current and adult-onset asthma, adjusting for age, sex,
      smoking, and deprivation. Analyses were also stratified by sex, smoking status,
      body mass index, and age group. RESULTS: Results were based on 2903 interviews.
      Participants with very or extremely stressful jobs were twice as likely to have
      current asthma (OR = 1.98; 95% CI = 1.52-2.58) and 50% more likely to have adult
      onset asthma (OR = 1.50; 95% CI = 1.05-2.15) compared to those with not at all or
      mildly stressful jobs. This association was evident for both sexes and was not
      explained by either occupation, age, body mass index, or smoking, although the
      results did differ by smoking status. CONCLUSION: Our study adds to the sparse
      evidence on the relationship between work-related stress and asthma in adult
      working populations.

PMID- 21864094
TI  - International Forum for the Advancement of Diabetes Research and Care, April 29
      30, 2011, Athens, Greece.
AB  - The International Forum for the Advancement of Diabetes Research and Care brought
      together distinguished international experts in diabetes to discuss diverse
      trends and emerging issues in diabetes therapy and management. The plenary
      sessions on the first day focused on trends in insulin therapy, the role of
      glucagon-like peptide-1 receptor agonists in diabetes treatment, the relationship
      between diabetes and cardiovascular risk, and the challenges associated with the
      development of clinically relevant treatment guidelines. Interactive breakout
      sessions addressed the following topics: microvascular complications of diabetes;
      the need for a team approach to patient education; optimal management of Asian
      people with diabetes; the role of continuous glucose monitoring in assessing
      glucose variability; and lessons learned from biosimilar drugs. The plenary
      sessions on the second day covered self-monitoring of blood glucose, treatment
      and prevention of type 1 diabetes, and future directions for diabetes therapy.
      The meeting represented an excellent forum for the presentation of new research
      and the exchange of ideas aimed at improving outcomes for people with diabetes.

PMID- 21864098
TI  - Preparation and characterization of metformin hydrochloride loaded
      Eudragit(r)RSPO and Eudragit(r)RSPO/PLGA nanoparticles.
AB  - The aim of the present study was to develop and characterize metformin HCl-loaded
      nanoparticle formulations. Nanoparticles were prepared by the nanoprecipitation
      method using both a single polymer (Eudragit((r))RSPO) and a polymer mixture
      (Eudragit/PLGA). The mean particle size ranged from 268.8 to 288 nm and the
      nanoparticle surface was positively charged (9.72 to 10.1 mV). The highest
      encapsulation efficiency was observed when Eudragit(r)RSPO was used. All
      formulations showed highly reproducible drug release profiles and the in vitro
      drug release in phosphate buffer (pH = 6.8) ranged from 92 to 100% in 12 h. These
      results suggest that Eudragit((r))RSPO or Eudragit/PLGA nanoparticles might
      represent a promising sustained-release oral formulation for metformin HCl,
      reducing the necessity of repeated administrations of high doses to maintain
      effective plasma concentrations, and thus, increasing patient compliance and
      reducing the incidence of side-effects.

PMID- 21864099
TI  - Social media, text messaging, and email-preferences of asthma patients between 12
      and 40 years old.
AB  - BACKGROUND: Electronic media such as social media (Facebook, Twitter, MySpace),
      email, and text messaging could be useful in the management of asthma. However,
      patient use and preferences for electronic media in asthma management is
      currently unknown. METHODS: A survey was sent to asthma patients between 12-40
      years of age. The survey collected demographic information, use of electronic
      media, interest in using electronic media to receive asthma information, and
      interest in using electronic media to communicate with a health care provider
      about asthma. Free text entries were encouraged. RESULTS: 145 completed surveys
      were returned. Text messaging, email, and Facebook were used at least weekly by a
      majority of respondents (82%, 77%, and 65%, respectively). Email was clearly the
      most preferred method to receive asthma information and to communicate with a
      physician. There was some interest in using Facebook or text messaging, whereas
      Myspace and Twitter had minimal interest. On logistic regression analysis, female
      and Black or Hispanic participants were more likely to have an interest in the
      use of electronic media for asthma care. Frequent users (>1X/week) of each
      electronic media type had greater enthusiasm for their incorporation into asthma
      care. Free text entries revealed that many participants felt social media sites
      were for connecting with friends rather than for health care, and privacy
      concerns were also raised. CONCLUSION: Electronic media offers a novel way to
      improve asthma care. Email was the most preferred method, though text messaging
      and social media sites like Facebook may be appropriate for certain patients.

PMID- 21864101
TI  - Why do we need to make the case for disinfection of drinking water yet again?

PMID- 21864102
TI  - Spatial mapping of lead, arsenic, iron, and polycyclic aromatic hydrocarbon soil
      contamination in Sydney, Nova Scotia: community impact from the coke ovens and
      steel plant.
AB  - This paper presents spatial maps of the arsenic, lead, and polycyclic aromatic
      hydrocarbon (PAH) soil contamination in Sydney, Nova Scotia, Canada. The spatial
      maps were designed to create exposure cohorts to help understand the observed
      increase in health effects. To assess whether contamination can be a proxy for
      exposures, the following hypothesis was tested: residential soils were impacted
      by the coke oven and steel plant industrial complex. The spatial map showed
      contaminants are centered on the industrial facility, significantly correlated,
      and exceed Canadian health risk-based soil quality guidelines. Core samples taken
      at 5-cm intervals suggest a consistent deposition over time. The concentrations
      in Sydney significantly exceed background Sydney soil concentrations, and are
      significantly elevated compared with North Sydney, an adjacent industrial
      community. The contaminant spatial maps will also be useful for developing
      cohorts of exposure and guiding risk management decisions.

PMID- 21864103
TI  - Effects on pulmonary health of neighboring residents of concentrated animal
      feeding operations: exposure assessed using optimized estimation technique.
AB  - Potential adverse health effects of concentrated animal feeding operations
      (CAFOs), which were also shown in the authors' Lower Saxony Lung Study, are of
      public concern. The authors aimed to investigate pulmonary health effect of
      neighboring residents assessed using optimized estimation technique. Annual
      ammonia emission was measured to assess the emission from CAFO and from
      surrounding fields. Location of sampling points was optimized using cluster
      analysis. Individual exposure of 457 nonfarm subjects was interpolated by
      weighting method. Mean estimated annual ammonia levels varied between 16 and 24
      MUg/m3. Higher exposed participants were more likely to be sensitized against
      ubiquitous allergens as compared to lower exposed subjects (adjusted odds ratio
      [OR] 4.2; 95% confidence interval [CI] 1.2-13.2). In addition, they showed a
      significantly lower forced expiratory volume in 1 second (FEV1) (adjusted mean
      difference in % of predicted -8%; 95% CI -13% to -3%). The authors' previous
      findings that CAFOs may contribute to burden of respiratory diseases were
      confirmed by this study.

PMID- 21864104
TI  - Fine particulate matter (PM2.5) air pollution and immune status among women in
      the Seattle area.
AB  - Changes in immune status have been suggested as a possible biologic mechanism by
      which particulate matter (PM) air pollution could lead to adverse health effects.
      The authors studied associations between ambient PM2.5 and immune status among
      115 postmenopausal, overweight women in the greater Seattle, Washington, area.
      The authors evaluated 3-day, 30-day, and 60-day average PM2.5 values in relation
      to inflammation markers (C-reactive protein, serum amyloid A, interleukin-6) and
      functional assays of cellular immunity (natural killer cell cytotoxicity, T
      lymphocyte proliferation) at 3 time points for each woman during 1 year. Three
      day averaged PM2.5 was inversely associated with anti-CD3-stimulated lymphocyte
      proliferation. There were no notable associations between the inflammation
      markers and PM2.5. If additional studies confirm our findings, then future health
      effect assessments for PM2.5 should consider changes in cellular immunity as an
      endpoint that may lead to overt clinical disease.

PMID- 21864105
TI  - Visual contrast sensitivity in children exposed to tetrachloroethylene.
AB  - This study examined relationships between indoor air, breath, and blood
      tetrachloroethylene (perc) levels and visual contrast sensitivity (VCS) among
      adult and child residents of buildings with or without a colocated dry cleaner
      using perc. Decreasing trends in proportions of adults or children with maximum
      VCS scores indicated decreased VCS at a single spatial frequency (12 cycles per
      degree [cpd]) among children residing in buildings with colocated dry cleaners
      when indoor air perc level averaged 336 MUg/m3; breath perc level averaged 159.5
      MUg/m3; and blood perc level averaged 0.51 MUg/L. Adjusted logistic regression
      indicated that increases in indoor air, breath, and blood perc levels among all
      child participants significantly increased the odds for decreased VCS at 12 cpd.
      Adult VCS was not significantly decreased by increasing indoor air, breath, or
      blood perc level. These results suggest that elevated residential perc exposures
      may alter children's VCS, a possible subclinical central nervous system effect.

PMID- 21864106
TI  - Job activities and respiratory symptoms among farmworkers in North Carolina.
AB  - Respiratory health is an important component of the ability to perform physically
      demanding work. The authors assessed respiratory symptom prevalence among Latino
      farmworkers engaged in crop production, and investigated work activities as risk
      factors for respiratory symptoms. During June to September 2008, 122 farmworkers
      completed up to 3 questionnaires. The authors estimated associations between work
      activities and wheezing symptoms using alternating logistic regression,
      controlling for age and smoking. At the first data collection, 29 (24%)
      farmworkers reported ever wheezing and 10 (8%) reported wheezing within the past
      month. Though not statistically significant, the odds of wheezing were elevated
      for individuals who reported performing tobacco-related work in the last 3 days.
      The odds were decreased among individuals who reported harvesting activities
      (odds ratio: 0.3, 95% confidence interval: 0.1, 1.0). Among Latino farmworkers,
      respiratory symptoms may be associated with work activities.

PMID- 21864107
TI  - From "Occupational" to "Industrial": issue 1 of the AMA Archives of Industrial
      Health, January 1955.

PMID- 21864109
TI  - The literal meaning of health.

PMID- 21864110
TI  - Mesenchymal stem cells as immunomodulator therapies for immune-mediated systemic
      dermatoses.
AB  - Mesenchymal stems cells (MSCs) are a population of multipotent cells residing in
      several readily available adult tissue compartments, thus allowing for their ex
      vivo expansion. To date, therapeutic applications of MSCs have focused on their
      ability to hone to and support the repair of damaged tissues. More recent
      evidence suggests that MSCs possess low immunogenicity and a diverse array of
      immunosuppressive properties. In thisarticle, we will review the basic biology of
      bone marrow-derived MSCs including their immunoregulatory effects and the
      putative mechanisms underlying them. We will then present some of the recent
      clinical applications of MSCs that have leveraged these effects for the treatment
      of immune-mediated dermatoses such as graft-versus-host disease and systemic
      lupus erythematosus. Although MSCs offer great therapeutic promise, we will also
      highlight a number of pertinent challenges that should be overcome before their
      successful clinical translation.

PMID- 21864111
TI  - Development and evaluation of novel microemulsion based oral formulations of 5
      fluorouracil using non-everted rat intestine sac model.
AB  - Oral formulations of 5-fluorouracil (5-FU) with enhanced bioavailability were
      developed using microemulsion as a drug carrier system. The formulations were
      evaluated for drug content, physicochemical characteristics such as globule size,
      zeta potential, viscosity, stability and permeation characteristics. Ex vivo
      permeation studies were performed using non-everted rat intestinal sac technique.
      Results of the ex vivo permeation studies revealed that from aqueous solution
      only 25.08% drug was permeated, whereas, the optimized microemulsion formulation
      showed 97.5% drug permeation in 8 h, suggesting, approximately, four times
      enhancement in the drug permeability. Also a 7-fold increase in the flux of drug
      was observed from microemulsion formulation when compared with the aqueous
      solution. Further, in vivo pharmacodynamic studies were carried to check the
      therapeutic efficacy against benzo(a)pyrene [B(a)P]-induced stomach tumors in
      albino mice (Balb/C strain). The treatment of mice with 5-FU and microemulsion (5
      FU II), after the last dose of B(a)P i.e. during the initiation period, resulted
      in 25% and 67% reduction in tumor incidence, respectively suggesting significant
      enhancement in the bioavailability and therapeutic efficacy of 5-FU when it was
      formulated as a microemulsion. These promising results suggest that microemulsion
      formulation of 5-FU may be used for the treatment of human cancers after
      pharmacokinetic and clinical evaluation.

PMID- 21864112
TI  - Comparative analysis of the methods of drug and protein delivery for the
      treatment of cancer, genetic diseases and diagnostics.
AB  - The methods of protein and drug delivery for the treatment of cancer, genetic
      diseases and diagnostics were summarized. The potential of protein transduction
      is discussed and the recent developments in the field are reviewed. An overview
      is provided of the non-viral delivery methods such as liposomes, polymer-based
      delivery, cell-penetrating peptides, bacterial secretion, cells, virosomes,
      physical methods including electroporation, microinjection, osmotic lysis,
      nanoparticles, sonoporation to locally inject therapeutic molecules. The
      characteristic properties of non-viral vectors and their use for the delivery of
      therapeutic molecules for the diagnosis and treatment of disorders and to target
      tumors are also discussed. The potential of the transduced peptides and proteins
      was used as new therapeutic compounds against infectious diseases, to complement
      deficiencies in specific genes, to specifically kill tumour cells, for gene
      therapy. The protein delivery vectors can enhance the transfection at low
      concentrations and help to develop future gene delivery systems with reduced
      toxicity. Vitamin B12, folic acid, biotin, and riboflavin are essential in the
      treatment of cancer. Ultrasound has a potential in the delivery of therapeutic
      agents. The new developing technologies of drug delivery and targeting offer the
      possibility to improve the therapeutic possibilities of the existing drugs and to
      develop novel therapeutics.

PMID- 21864114
TI  - Inactivation of TLR9 by a suppressive oligodeoxynucleotides can ameliorate the
      clinical signs of EAN.
AB  - Susceptible-strain animals immunized with P2 peptide could generate the disease
      of experimental autoimmune neuritis (EAN) with inflammation and demyelination of
      peripheral nerve. A myriad of transcription factors and inflammatory cytokines
      have been found to participate in this process; however, the roles of toll-like
      receptors (TLRs) are poorly understood in EAN. The aim of this study is to
      explore the role of TLR9 in the pathogenesis of EAN. The EAN was induced in Lewis
      rat by immunization with P2(53-78) and complete Freund's adjuvant. CpG
      oligodeoxynucleotides (ODN) (cODN), a suppressive ODN (sODN) and a control non
      specific ODN (nODN) were respectively administered to explore the role of TLR9 in
      EAN both in vivo and vitro. Following immunization up to the peak phase of EAN,
      EAN rats inoculated with sODN had remarkably better clinical score of EAN and
      expressed a significantly inhibited TLR9 signaling pathway. Our study suggests
      that TLR9 may be involved in the pathogenesis of EAN.

PMID- 21864113
TI  - Suppression of MMP-9 expression in brain microvascular endothelial cells (BMVEC)
      using a gold nanorod (GNR)-siRNA nanoplex.
AB  - Inhibition of Matrix metalloproteinase-9 (MMP-9) activity using delivery of short
      interfering RNA (siRNA) molecules to brain microvascular endothelial cells
      (BMVECs) that constitute the BBB may have a significant impact on reducing the
      BBB permeability. Gold nano rods (GNRs) can electrostatically bind with MMP-9
      siRNA to form a nanoplex and the uptake of this nanoplex by BMVEC cells can
      result in suppression of MMP-9 expression. The current study explores if this GNR
      MMP-9 siRNA nanoplex gene silencing modulates the expression of tight junction
      (TJ) proteins in the BMVEC. The endothelial TJ's of the BBB play a critical role
      in controlling cellular traffic into the central nervous system. We hypothesize
      that silencing of the MMP-9 gene expression in BMVEC will increase the expression
      of TJ proteins thereby decrease endothelial permeability. Our results showed a
      significant increase in the gene and protein expression of TJ proteins: ZO-1,
      Occludin and Claudin-5 in BMVEC cells that were transfected with the GNRs-siRNA
      MMP-9 nanoplex suggesting that BBB disruption, which results from loss of TJ
      function due to MMP-9 activation during neuroinflammation can be prevented by
      silencing MMP-9 expression.

PMID- 21864115
TI  - Comparison of liposome-polycation-DNA(LPD) and monophosphoryl lipid A(MPL)
      adjuvant formulations in BALB/c mice models.
AB  - It is of fundamental importance to use an appropriate adjuvant to generate a
      potent immune response for immunotherapy. In this study, we had a comparative
      investigation on the effectiveness of two adjuvant formulations, liposome
      polycation-DNA (LPD) and monophosphoryl lipid A(MPL) in combination with a
      truncated peptide of bFGF(tbFGF) as antigen. LPD/tbFGF induced continuously
      increasing antibodies expression during the whole immunization period. In
      contrast, the level of antibodies was variable in MPL/tbFGF-immunized mice,
      MPL/tbFGF elicited potent antibodies response in the early-phase of immunization
      (during the first 3 immunizations), but the later immunizations did not produce a
      significant increase in the level of antibodies. Evaluation of IFN-gamma and IL-4
      responses revealed that both LPD/tbFGF and MPL/tbFGF demonstrated generation of
      higher level of IFN-gamma, whereas no significant increase in IL-4 levels was
      detected in the two groups. In addition, histological analysis exhibited obvious
      germinal centers in the spleen tissues of LPD/tbFGF mice. The data suggested that
      LPD would be a promising long-effective adjuvant due to its potent and persistent
      immunostimulation and MPL could play an appropriate role in short-acting
      immunization.

PMID- 21864116
TI  - Co-morbidities and 90-day outcomes in hospitalized COPD exacerbations.
AB  - COPD exacerbations resulting in hospitalization are accompanied by high mortality
      and morbidity. The contribution of specific co-morbidities to acute outcomes is
      not known in detail: existing studies have used either administrative data or
      small clinical cohorts and have provided conflicting results. Identification of
      co-existent diseases that affect outcomes provides opportunities to address these
      conditions proactively and improve overall COPD care. Cases were identified
      prospectively on admission then underwent retrospective case note audit to
      collect data including co-morbidities on up to 60 unselected consecutive acute
      COPD admissions between March and May in each hospital participating in the 2008
      UK National COPD audit. Outcomes recorded were death in hospital, length of stay,
      and death and readmission at 90 days after index admission. 232 hospitals
      collected data on 9716 patients, mean age 73, 50% male, mean FEV1 42% predicted.
      Prevalence of co-morbidities were associated with increased age but better FEV1
      and ex-smoker status and with worse outcomes for all four measures. Hospital
      mortality risk was increased with cor pulmonale, left ventricular failure,
      neurological conditions and non-respiratory malignancies whilst 90 day death was
      also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases
      were important factors in readmission. This study demonstrates that co
      morbidities adversely affect a range of short-term patient outcomes related to
      acute admission to hospital with exacerbations of COPD. Recognition of relevant
      accompanying diseases at admission provides an opportunity for specific
      interventions that may improve short-term prognosis.

PMID- 21864117
TI  - A singular case of congenital self-healing histiocytosis with skin, liver and
      atypical eye involvement.
AB  - PURPOSE: To describe a rare case of congenital self-healing Langerhans cell
      histiocytosis (CSHLCH) presenting with atypical eye involvement. DESIGN: Case
      report. METHODS: A female newborn presented with purpuric lesions over the trunk,
      limbs, and face. Liver ultrasonography revealed hypoechogenic lesions with
      blurred borders. Biomicroscopy showed right posterior synechiae with fibrinoid
      deposits on the lens. At 7 months she presented with right acute glaucoma.
      RESULTS: Biomicroscopy showed the presence of inflammatory pseudo-membrane
      covering the anterior surface of the lens, iris, and iridocorneal angle. Ab
      externo trabeculotomy was performed; access to the anterior chamber with
      capsulorrhexis forceps permitted a peeling of the pseudo-membrane with
      normalization of the intraocular pressure. Histologic examination of the membrane
      revealed an inflammatory tissue with CD1a and S-100 positive histiocytic cells.
      CONCLUSIONS: This is the first case of CSHLCH describing acute glaucoma secondary
      to a pseudo-inflammatory membrane with typical histiocytic cells, occluding the
      iridocorneal angle.

PMID- 21864118
TI  - Clinical, tomographic, and angiographic findings in patients with acute
      toxoplasmic retinochoroiditis and associated serous retinal detachment.
AB  - PURPOSE: To describe the clinical, optical coherence tomographic, and
      angiographic findings in patients with acute toxoplasmic retinochoroiditis (RC)
      associated with serous retinal detachment (SRD). METHODS: The study included 60
      eyes with acute toxoplasmic RC. RESULTS: Of 60 eyes, 14 (23.3%) were found to
      have SRD. The SRD was visible on fundus examination in 6 cases and detectable
      only by optical coherence tomography (OCT) in the 8 remaining cases. It involved
      the fovea in 9 eyes. There was evidence of associated choroidal ischemia on
      fluorescein angiography and indocyanine green angiography in 5 eyes. Findings
      seen at the acute stage gradually resolved over a period of 2-6 weeks in all
      patients. CONCLUSIONS: SRD, accurately detected by OCT, is a common complication
      of acute toxoplasmic RC that should be considered as a potential cause of visual
      loss. Choroidal ischemia might contribute to the development of such
      complication.

PMID- 21864119
TI  - A case of severe dysmelia of all extremities.
AB  - A group of limb reduction defects is defined by congenital absence of either part
      of limbs. We report an extremely rare case of symmetrical upper limb peromelia
      (absence of distal bones) and asymmetrical lower limb phocomelia (absence of long
      bones and a flipper-like appearance of feet) in a female fetus at the 20th week
      of pregnancy. No other malformations were identified. The prevalence of peromelia
      and phocomelia is extremely rare, and these malformations can be associated with
      some candidate genes (e.g. de novo apparently balanced reciprocal translocation
      46,XX,t(2;12)(p25.1;q24.1)).

PMID- 21864120
TI  - Perilobar nephrogenic rests and chromosome 22.
AB  - Perilobar nephrogenic rests (NR) are precursor lesions that may display genetic
      changes similar to their associated Wilms tumor (WT). Two patients presented with
      WT, both with perilobar NR and 1 with bilateral, multifocal metachronous WT. Both
      patients' WT displayed monosomy 22 as the predominant cytogenetic change, and the
      constitutional cytogenetic analysis was normal. The purpose of our study was to
      identify at what stage in the morphologic progression from NR to WT the monosomy
      22 occurred by using a fluorescent in situ hybridization probe for chromosome 22
      in the subtypes of perilobar NR and WT present in both cases. Section and core
      fluorescent in situ hybridization with a chromosome 22 probe was performed on
      formalin-fixed, paraffin-embedded tissues containing WT and perilobar NR. We also
      performed fluorescent-based microsatellite analysis on some of the WT in the
      bilateral case to determine whether there was a preferential loss of the same
      allele of chromosome 22. Sclerotic and dormant perilobar NR showed a rate of
      monosomy 22 of only approximately 30%, but this increased to approximately 50% in
      hyperplastic and adenomatous NR. Monosomy 22 was present in 60%-80% of nuclei in
      WT. Microsatellite analysis showed loss of homozygosity, with preferential loss
      of the same allele of chromosome 22 in the tumors examined. There are differences
      in the rate of detection of monosomy 22 in perilobar NR and WT, suggesting loss
      of chromosome 22 in the progression of perilobar NR to WT in a subset of tumors.

PMID- 21864121
TI  - Utility of diagnosing various histological patterns of diffuse chronic hypoxic
      placental injury.
AB  - To examine the clinicopathologic correlations of three histological patterns of
      diffuse chronic hypoxic placental injury (preuterine [PR], uterine [UH], and
      postuterine [PU]), a retrospective statistical analysis of a large 14-year
      placental database was performed. Of 5097 placentas between 20 and 43 weeks of
      gestation examined consecutively, 4413 did not feature histological chronic
      placental hypoxia, while 684 did. In the latter, maternal hypertensive disorders,
      diabetes mellitus, abnormal cardiotocography and Dopplers, cesarean sections,
      inductions of labor, and fetal growth restriction, as well as other placental
      hypoxic lesions and decidual arteriolopathy, were statistically significantly
      more common than in the remaining placental material. Two hundred eighty-nine PR
      cases featured the most advanced gestational age and meconium staining; 237 UH
      cases featured severe preeclampsia, decidual arteriolopathy, villous infarction,
      membrane laminar necrosis, microscopic chorionic pseudocysts, excessive
      extravillous trophoblasts, and maternal floor multinucleate trophoblastic giant
      cells; and 158 PU cases featured the lowest placental weight and the highest
      prevalence of abnormal Dopplers, umbilical cord compromise, fetal growth
      restriction, cesarean section rate, and complicated 3rd stage of labor. The
      specificity of chronic hypoxic patterns of placental injury was much higher than
      the sensitivity, with the highest specificity for an excessive amount of
      extravillous trophoblasts. Diagnosing various hypoxic patterns of placental
      injury by histology may help to clarify the etiopathogenesis of a significant
      proportion of complications of pregnancy and abnormal fetal or neonatal outcomes.
      The patterns should help to retrospectively diagnose placental hypoxia, even in
      clinically unsuspected cases.

PMID- 21864122
TI  - Placental and fetal findings in intrauterine Candida lusitaniae infection
      following in vitro fertilization and embryo transfer.
AB  - Intrauterine infection with non- albicans Candida species is rare but can be
      catastrophic to the fetus. A subset of intrauterine infections with non- albicans
      Candida species has occurred in women who have undergone in vitro fertilization
      and embryo transfer (IVF-ET). We report a case of a 33-year-old healthy woman,
      pregnant with triplets by in vitro fertilization, who experienced preterm
      premature rupture of membranes of fetus A at 16 weeks' gestation and subsequently
      developed oligohydramnios in all 3 fetuses. Following elective pregnancy
      termination, microscopic examination and molecular analysis demonstrated Candida
      lusitaniae chorioamnionitis and pneumonia in all 3 fetuses associated with
      granulomatous inflammation. Our case is only the 2nd report of C. lusitaniae
      chorioamnionitis and should raise awareness that C. lusitaniae intrauterine
      infection is associated with IVF-ET. We also show here that C. lusitaniae can
      cause granulomatous intraplacental inflammation and intrauterine pneumonia.

PMID- 21864123
TI  - Modified technique for vital bleaching of teeth pigmented by amalgam: a case
      report.
AB  - The aim of this study was to describe a technique and report the success of a
      clinical case in which a modified technique of in-office bleaching with hydrogen
      peroxide at 35% was performed for two sessions in a premolar pigmented by amalgam
      followed by placement of a posterior direct composite resin restoration.

PMID- 21864124
TI  - Bonding to glass ionomer cements using resin-based adhesives.
AB  - OBJECTIVE: This study compared the microshear bond strengths (MSBS) of four self
      etching adhesives (Adper Scotchbond SE [SSE], Clearfil SE Bond [CSE], Clearfil S3
      Bond [CS3] and One Coat 7.0 [OC]) and an etch-and-rinse adhesive (Adper Single
      Bond Plus [SB]) when bonded to two conventional glass ionomer cements (GICs)
      (Fuji IX GP EXTRA and Riva Self Cure). The null hypothesis tested was there is no
      difference in the adhesive ability of an etch-and-rinse adhesive and self-etching
      adhesives when bonded to GIC for up to 6 months. METHODS: The GICs were embedded
      in type III dental stone and wet ground with 1200-grit SiC paper. Twenty
      specimens were bonded for each adhesive according to manufacturers' instructions
      with a 1.5-mm bonding diameter. Specimens were stored at 100% humidity for 24
      hours, 1 month, or 6 months. Microshear bond strengths were obtained using a
      crosshead speed of 1 mm/min. The results were calculated and analyzed using
      analysis of variance (ANOVA) and Tukey HSD test. RESULTS: SB had significantly
      lower MSBS than the four self-etching adhesives for all storage periods. MSBS at
      6 months for SB was significantly lower than at 1 month. There were no
      significant differences in MSBS among the self-etching adhesives. Cohesive
      failure within GIC was the most common failure mode observed. CONCLUSIONS: SB
      showed a lower bond strength than the self-etching adhesives when bonded to
      conventional GICs for all storage periods. This might be a result of the
      phosphoric acid etching. However, cohesive strength of GIC was a limiting factor
      for the MSBS outcomes.

PMID- 21864125
TI  - Dual and self-curing potential of self-adhesive resin cements as thin films.
AB  - In this study, the dual- and self-curing potential of self-adhesive resin cements
      (SARCs) as thin, clinically-relevant cement films was investigated. The SARCs
      tested were: BisCem (BSC; Bisco), Maxcem Elite (MXE; Kerr), RelyX Unicem clicker
      (UNI; 3M ESPE), seT capsule (SET; SDI), and SmartCem 2 (SC2; Dentsply Caulk). The
      conventional cement RelyX ARC (3M ESPE) was tested as a reference. The degree of
      conversion (DC) as a function of time was evaluated by real-time Fourier
      transform infrared spectroscopy with an attenuated total reflectance (ATR)
      device. The cements were either photoactivated for 40 seconds (dual-cure mode) or
      not photoactivated (self-cure mode). The cement film thickness was 50 +/- 10 MUm.
      The DC (%) was evaluated 1, 5, 10, 15, 20, 25, and 30 minutes after placing the
      cement on the ATR cell. Data for DC as a function of time were analyzed by two
      way repeated measures analysis of variance (ANOVA). DC values at 30 minutes for
      the self- and dual-cure modes were submitted to one-way ANOVA. Post hoc
      comparisons were performed using the Student-Newman-Keuls test (p<0.05). The rate
      and the extent of conversion were lower for the SARCs compared with the
      conventional cement. Means +/- standard deviations (SD) for the dual-cure mode at
      30 minutes were: 75 +/- 5 (ARC)a, 73 +/- 8 (SET)a, 61 +/- 4 (MXE)b, 51 +/- 9
      (BSC)c, 51 +/- 4 (UNI)c, and 48 +/- 3 (SC2)c, while in the self-cure mode means
      and SD were 62 +/- 6 (ARC)a, 54 +/- 3 (MXE)b, 40 +/- 6 (SC2)c, 35 +/- 2 (UNI)c,
      35 +/- 3 (SET)c, and 11 +/- 3 (BSC)d. The DC for the dual-cure mode was generally
      higher than the self-cure, irrespective of the time. Discrepancies in DC between
      the dual- and self-cure modes from 11% to 79% were observed. In conclusion, SARCs
      may present slower rate of polymerization and lower final DC than conventional
      resin cements, in either the dual- or self-cure mode.

PMID- 21864126
TI  - Bond strength evaluation of three self-adhesive luting systems used for cementing
      composite and porcelain.
AB  - Self-adhesive resin cements were recently introduced with the purpose of
      simplifying the cementation technique, as they combine the use of adhesive and
      cement in a single application, eliminating the need for pretreatment of the
      tooth. In the present study a microtensile bond strength test (MU-TBS) was used
      to compare three self-adhesives, an etch-and-rinse and a self-etch luting system,
      in the cementation of resin-based composite (RBC) and ceramic disks to dentin.
      Freshly extracted molars were transversally sectioned to expose flat, deep dentin
      surfaces. Cylindrical specimens (5 mm in diameter and 10 mm in height),
      consisting of RBC disks and leucite-based glass ceramic disks, were produced. The
      RBC disks were sandblasted with 50-MUm Al2O3. The ceramic disks were conditioned
      with 9.5% hydrofluoric acid gel and silane application. All of the disks were
      then bonded to dentin surfaces employing five different luting agents: iCEM Self
      Adhesive (Heraeus Kulzer), MaxCem (Kerr Corporation), RelyX UniCem (3M ESPE),
      EnaCem HF (Micerium), and Panavia F2.0 (Kuraray-Dental). The products were
      applied according to the manufacturers' instructions. The specimens were
      sectioned perpendicular to the adhesive interface to produce multiple beams
      measuring approximately 1 mm2 in cross section. For each experimental group 12
      beams were tested. The preterm failures were also taken into account. All of the
      specimen preparations were performed by the same operator. The beams were tested
      under tension at a crosshead speed of 0.5 mm/min until failure. Mean MU-TBS
      values were calculated for each group. Data were analyzed by a two-way analysis
      of variance, and multiple comparisons were performed using a Tukey test
      (alpha=0.05). The UniCem group showed the lowest number of preterm failures among
      the tested self-adhesive systems. When premature debondings were included in the
      mean value calculation, bond strength values for the UniCem group were
      statistically equal to or even higher than those achieved with the other self
      adhesives, although these values were still statistically worse than those
      obtained using traditional multi-step luting agents.

PMID- 21864127
TI  - The influence of time and cement type on push-out bond strength of fiber posts to
      root dentin.
AB  - The bond strength of fiber posts luted with resin cements was evaluated after two
      storage times in different regions of a post space. A total of 40 single-rooted
      human teeth were endodontically treated and prepared for cementation of fiber
      posts (White Post DC). In groups 1 and 3 (G1 and G3, respectively), posts were
      luted with RelyX ARC, whereas the posts in groups 2 and 4 (G2 and G4,
      respectively) were luted with RelyX Unicem. After one month of storage at 100%
      humidity, G1 and G2 were transversally sectioned in 1.7-mm slices of the cervical
      (C), middle (M), and apical (A) thirds of the post space and submitted to push
      out testing at 1 mm/min. After nine months of storage, the roots of G3 and G4
      underwent the same process. Mean values were analyzed using the Mann-Whitney and
      Kruskal-Wallis tests (alpha=0.05). The bond strengths in G2 (C=4.26+/-2.29;
      M=4.67+/-3.54; A=7.27+/-4.30) were statistically higher than in G1 (C=3.81+/
      1.07; M=1.57+/-1.62; A=1.99+/-1.60) in the middle and apical thirds (p=0.001).
      Bond strengths in G4 (C=3.36+/-1.39; M=4.49+/-2.17; A=3.83+/-1.92) were higher
      than in G3 (C=2.13+/-0.47; M=0.94+/-1.05; A=0.95+/-1.02) in all evaluated regions
      (p=0.02, p<0.001, and p<0.001, respectively). When comparing the root regions for
      each group, G1 had higher values in the cervical third than the middle third
      (p=0.02). The self-adhesive resin cement showed better results than the
      conventional resin cement at both storage times. For both materials a similar
      performance among the three root regions was found. Storage time did not
      influence the shear bond strength.

PMID- 21864129
TI  - Helminth community structure of Tropidurus torquatus (Squamata: Tropiduridae) in
      a rocky outcrop area of Minas Gerais state, southeastern Brazil.
AB  - The helminth community of Tropidurus torquatus (Squamata: Tropiduridae) from a
      rocky outcrop area located in the state of Minas Gerais, southeastern Brazil, was
      studied. Ninety-two of the 110 individuals examined (83.6%) harbored helminths.
      Five species were found, including 3 nematodes ( Physaloptera lutzi ,
      Parapharyngodon bainae , and Oswaldofilaria chabaudi ), 1 unidentified cestode
      species, and 1 acanthocephalan cystacanth also not identified. Only the nematode
      species had sufficient data to perform ecological analysis, with P. lutzi
      exhibiting the highest prevalence (67.3%). Prevalence between male and female
      hosts differed only for Oswaldofilaria chabaudi , with males exhibiting the
      highest values. The intensities of infection by P. lutzi and O. chabaudi were
      different among male and female hosts, with males also exhibiting the highest
      values. The host body size was positively related to intensity of infection for
      all nematode species. Local seasonality had some influence on the helminth
      community structure. Host diet, sexual dimorphism, and behavior (territorialism,
      forage strategy) represented important factors for the structure of this parasite
      community. In general, the helminth community was species poor, depauperate, and
      non-interactive, representing a typical structure observed in lizard hosts.

PMID- 21864128
TI  - Effect of chlorhexidine pretreatment on bond strength durability of caries
      affected dentin over 2-year aging in artificial saliva and under simulated
      intrapulpal pressure.
AB  - OBJECTIVE: To evaluate the influence of 2% and 5% chlorhexidine (CHX)
      pretreatment on bond durability of a self-etching adhesive to normal (ND) and
      caries-affected (AD) dentin after 2-years of aging in artificial saliva and under
      simulated intrapulpal pressure (IPP). METHODS: One hundred twenty freshly
      extracted carious teeth were ground to expose ND and AD. Specimens were
      distributed into three equal groups (n=40) according to whether the dentin
      substrates were pretreated with 2% or 5% CHX or with water (control). Clearfil SE
      Bond (Kuraray) was applied to both substrates and composite cylinders (0.9 mm
      diameter and 0.7 mm height) were formed. Pretreatment and bonding were done while
      the specimens were subjected to 15 mm Hg IPP. After curing, specimens were aged
      in artificial saliva at 37 degrees C and under IPP at 20 mm Hg until being tested
      after 24 hours or 2 years (n=20/group). Microshear bond strength was evaluated.
      Failure modes were determined using a scanning electron microscope (SEM) at 400*
      magnification. Data were statistically analyzed using three-way analysis of
      variance (ANOVA); one-way ANOVA tests, and t-test (p<0.05). Additional specimens
      (n=5/group) were prepared to evaluate interfacial silver precipitation. RESULTS:
      For the 24-hour groups, there were no significant differences among the ND groups
      and AD groups. For ND aged specimens, the 5% CHX group had the highest value
      followed by the 2% CHX and control groups, although the difference was
      statistically insignificant. For AD aged specimens, the 5% CHX group revealed
      statistically higher bond values compared to the 2% CHX and control groups.
      Fracture modes were predominately adhesive and mixed. Different interfacial
      silver depositions were recorded. CONCLUSIONS: Two percent or 5% CHX pretreatment
      has no adverse effect on the 24-hour bonding to ND and AD. Five percent CHX was
      able to diminish the loss in bonding to AD after 2years of aging in artificial
      saliva and under simulated IPP.

PMID- 21864130
TI  - Widespread dispersal of Borrelia burgdorferi-infected ticks collected from
      songbirds across Canada.
AB  - Millions of Lyme disease vector ticks are dispersed annually by songbirds across
      Canada, but often overlooked as the source of infection. For clarity on vector
      distribution, we sampled 481 ticks (12 species and 3 undetermined ticks) from 211
      songbirds (42 species/subspecies) nationwide. Using PCR, 52 (29.5%) of 176 Ixodes
      ticks tested were positive for the Lyme disease spirochete, Borrelia burgdorferi
      s.l. Immature blacklegged ticks, Ixodes scapularis , collected from infested
      songbirds had a B. burgdorferi infection prevalence of 36% (larvae, 48%; nymphs,
      31%). Notably, Ixodes affinis is reported in Canada for the first time and,
      similarly, Ixodes auritulus for the initial time in the Yukon. Firsts for bird
      parasitizing ticks include I. scapularis in Quebec and Saskatchewan. We provide
      the first records of 3 tick species cofeeding on passerines (song sparrow,
      Swainson's thrush). New host records reveal I. scapularis on the blackpoll
      warbler and Nashville warbler. We furnish the following first Canadian reports of
      B. burgdorferi-positive ticks: I. scapularis on chipping sparrow, house wren,
      indigo bunting; I. auritulus on Bewick's wren; and I. spinipalpis on a Bewick's
      wren and song sparrow. First records of B. burgdorferi-infected ticks on
      songbirds include the following: the rabbit-associated tick, Ixodes dentatus, in
      western Canada; I. scapularis in Quebec, Saskatchewan, northern New Brunswick,
      northern Ontario; and Ixodes spinipalpis (collected in British Columbia). The
      presence of B. burgdorferi in Ixodes larvae suggests reservoir competency in 9
      passerines (Bewick's wren, common yellowthroat, dark-eyed junco, Oregon junco,
      red-winged blackbird, song sparrow, Swainson's thrush, swamp sparrow, and white
      throated sparrow). We report transstadial transmission (larva to nymph) of B.
      burgdorferi in I. auritulus. Data suggest a possible 4-tick, i.e., I. angustus,
      I. auritulus, I. pacificus, and I. spinipalpis, enzootic cycle of B. burgdorferi
      on Vancouver Island, British Columbia. Our results suggest that songbirds
      infested with B. burgdorferi-infected ticks have the potential to start new tick
      populations endemic for Lyme disease. Because songbirds disperse B. burgdorferi
      infected ticks outside their anticipated range, health-care providers are advised
      that people can contract Lyme disease locally without any history of travel.

PMID- 21864131
TI  - Identification of gene expression elements in Histomonas meleagridis using
      splinkerette PCR, a variation of ligated adaptor PCR.
AB  - Histomonas meleagridis is the causative agent of blackhead disease in
      gallinaceous birds. Limited genetic information exists for this organism, with
      the majority of sequence information coming from the coding regions of genes. No
      information is available for intergenic regions that contain DNA elements
      required for the regulation of gene expression. In this study, we demonstrate
      that splinkerette PCR, a variation of ligated adaptor PCR, can be used to
      identify regions of unknown sequence that lie upstream and downstream of known
      genomic sequences. Using this technique, we identified upstream sequences of 2
      beta-tubulin genes. Sequence analysis identified the 5' coding portions of the
      beta-tubulin genes, the intergenic regions, and 2 different open reading frames
      encoding for a putative serine/threonine phosphatase and a putative ras-related
      protein, racG. We predict that these intergenic regions contain polyadenylation
      and cleavage signals for the 2 open reading frames and initiator elements for the
      beta-tubulin genes. Our research demonstrates the use of splinkerette PCR as a
      valuable tool to identify unknown DNA sequences. In addition, the identification
      of the regulatory elements necessary for gene transcription in H. meleagridis
      will provide tools for future studies on its gene expression.

PMID- 21864132
TI  - Seroprevalence of Toxoplasma gondii infection in dogs in Sichuan Province,
      southwestern China.
AB  - There is a lack of information concerning the prevalence of Toxoplasma gondii
      infection in dogs from southwestern China. In the present study, serum samples
      from 314 household dogs were collected from Wenchuan, Heishui, and Jiuzhaigou in
      Sichuan Province, southwestern China, in May and June 201; sera were assayed for
      T. gondii antibodies using an indirect haemagglutination test (IHA). Antibodies
      to T. gondii were found in 11 of 314 (3.5%), with IHA titers of 1:64 in 4 dogs,
      1:128 in 3, 1:256 in 2, 1:512 in 1, and 1:1024 in 1. No regional difference was
      observed among the 3 counties (P > 0.05). The results of the present study
      indicated that infection with T. gondii in dogs is common in China, including
      household dogs in Sichuan Province, and should be of public health concern.

PMID- 21864133
TI  - The significance of small intestinal epithelium in gastric antral biopsies in
      children.
AB  - Intestinal metaplasia of the gastric antrum is common in adults with chronic
      gastritis and occurs in Helicobacter -associated gastritis in children. This
      study examined the frequency and clinical correlates of intestinal epithelium in
      1690 consecutive antral biopsies obtained from children over a 2-year period in a
      tertiary pediatric care facility. Intestinal epithelium in gastric glands not
      associated with overlying villi was present in 22 (1.3%) biopsies. These came
      from 20 patients, 2-17 years of age, none of whom had clinical or histologic
      evidence of Helicobacter infection or significant chronic gastritis. Eight (40%)
      had an antral pancreatic rest, 8 had some other localized antral abnormality, and
      4 were endoscopically normal. Four additional patients with a pancreatic rest had
      no intestinal epithelium. Six surgically resected rests and 2 rests found at
      autopsy were also reviewed. Heterotopic intestinal epithelium was present in 1 of
      the 2 postmortem specimens but was absent from all 6 surgically resected lesions.
      No intestinal epithelium was present in 67 antral biopsies with Helicobacter
      gastritis observed during this same period. Although the intestinal epithelium in
      these patients could be metaplastic, it more likely represents inadvertent
      sampling of the gastroduodenal junction induced by a lesion in the distal antrum
      or a focus of heterotopic epithelium and might best be addressed in the surgical
      pathology report by a comment to this effect. The distinction from metaplasia is
      more than semantic, because a diagnosis of intestinal metaplasia can have adverse
      clinical implications and should be made with caution in a child.

PMID- 21864134
TI  - Acute and chronic changes in diffusivity measures after sports concussion.
AB  - Despite negative neuroimaging findings in concussed athletes, studies indicate
      that the acceleration and deceleration of the brain after concussive impacts
      result in metabolic and electrophysiological alterations that may be attributable
      to changes in white matter resulting from biomechanical strain. In the present
      study we investigated the effects of sports concussion on white matter using
      three different diffusion tensor imaging (DTI) measures: fractional anisotropy
      (FA), mean diffusivity (MD), and axial diffusivity (AD). We compared a group of
      10 non-concussed athletes with a group of 18 concussed athletes of the same age
      (mean age 22.5 years) and education (mean 16 years) using a voxel-based approach
      (VBA) in both the acute and chronic post-injury phases. All concussed athletes
      were scanned 1-6 days post-concussion and again 6 months later in a 3T Siemens
      Trio(TM) MRI. Three 2*2 repeated-measures analyses of variance (ANOVAs) were
      conducted, one for each measure of DTI used in the current study. There was a
      main group effect of FA, which was increased in dorsal regions of both
      corticospinal tracts (CST) and in the corpus callosum in concussed athletes at
      both time points. There was a main group effect of AD in the right CST, where
      concussed athletes showed elevated values relative to controls at both time
      points. MD values were decreased in concussed athletes, in whom analyses revealed
      significant group differences in the CST and corpus callosum at both time points.
      Although the use of VBA does limit the analyses to large tracts, and it has
      clinical limitations with regard to individual analyses, our results nevertheless
      indicate that sports concussions do result in changes in diffusivity in the
      corpus callosum and CST that are not detected using conventional neuroimaging
      techniques.

PMID- 21864135
TI  - HRT and breast cancer risk: a realistic perspective.
AB  - A new analysis from the Women's Health Initiative included data on breast cancer
      incidence over a 11-year period from the randomized trial of conjugated equine
      estrogens (CEE) plus medroxyprogesterone acetate (MPA) and a subsequent
      observational follow-up. The conclusions were that CEE/MPA use was associated
      with an increase in both breast cancer incidence and mortality. We have concerns
      over the validity of their statistical analyses, as adjustments for baseline
      characteristics or for multiple comparisons demonstrate no significant
      differences in incidence between those allocated to CEE/MPA or placebo. We
      suspect that the apparent increase in mortality is the result of surveillance and
      detection bias rather than a true cause and effect. Even if such an effect were
      true, mortality from breast cancer would still be a very rare event. We also
      question the clinical relevance and applicability of their findings. The data
      over the 11 years show no increased risk of breast cancer with CEE/MPA in women
      who had not previously used hormone replacement therapy (HRT), and the vast
      majority of women on HRT would not be prior users at initiation. It should be
      remembered that women using CEE alone showed a significant decrease in breast
      cancer risk in the WHI trial and follow-up. Even if combined estrogen?progestogen
      HRT did cause an increase in breast cancer risk, and this is not proven, the
      magnitude of that risk is small, and less than that risk seen with many lifestyle
      factors. HRT is a benefit, not a risk, for those women requiring it.

PMID- 21864137
TI  - Effect of exercise combined with phytoestrogens on quality of life in
      postmenopausal women.
AB  - BACKGROUND: Postmenopausal women seem to favor alternative therapies such as
      exercise and phytoestrogens as a substitute for potentially harmful hormone
      replacement therapy. Based on previous research, we hypothesized that
      phytoestrogens combined with exercise could have a synergic effect on women's
      health. OBJECTIVE: To verify whether phytoestrogens enhance the response to mixed
      training regarding menopausal symptoms and quality of life in postmenopausal
      women. METHODS: From a pool of women participating in a 6-month randomized,
      controlled exercise study, 21 received a placebo (mean age 58.3 +/- 5.4 years,
      body mass index 29.8 +/- 5.1 kg/m(2)) and 19 received phytoestrogen supplements
      (mean age 60.1 +/- 3.4 years; body mass index 30.3 +/- 4.6 kg/m(2)). Body weight,
      fat mass and lean body mass (dual-energy X-ray absorptiometry) were assessed.
      Quality of life was estimated by the Short Form-36 (SF-36) and Perceived Stress
      Scale-10 (PSS-10) questionnaires, and menopausal symptoms by the Kupperman index.
      All measurements were performed before and after the intervention. RESULTS:
      Although the Kupperman index and PSS-10 remained unchanged in both groups, the SF
      36 Physical Component Summary and almost all the SF-36 subscales (except for role
      emotional and mental health) increased only in the exercise group taking
      phytoestrogens (0.001 < p < 0.04). CONCLUSION: While phytoestrogens combined with
      mixed exercise were not sufficient to improve menopausal symptoms, it seemed to
      be a better strategy than exercise alone to improve the general quality of life
      in postmenopausal women.

PMID- 21864136
TI  - Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model.
AB  - OBJECTIVE: The role of androgens in chronic disease pathogenesis, cognitive
      function and libido during menopause is of increasing interest. The aim of this
      study was to characterize the distribution and expression of androgenic proteins
      in the macaque ovary and to investigate the relationship between serum androgen
      concentrations, follicle number, and the persistence of androgenesis in the aging
      macaque ovary. METHODS: The subjects were 26 adult female cynomolgus macaques.
      Ovaries were immunostained for cytochrome P450 17alpha-hydroxylase/17-20 lyase
      (P450c17), 3beta-hydroxysteroid dehydrogenase (3betaHSD), and cytochrome b5
      (cytb5). Based on primordial follicle counts, animals were divided into tertiles
      (low (<=200), intermediate (226-1232), and high (2372-4356)) to evaluate
      differences in androgen staining and changes in serum androgen concentrations
      following ovariectomy. RESULTS: Positive immunostaining for P450c17 and cytb5
      within the theca interna layer of growing follicles persisted in advanced atretic
      follicles and secondary interstitial cells (residual stromal cells). Ovaries with
      low follicle numbers had less staining for all androgenic proteins compared to
      ovaries with higher numbers of growing follicles. Immunostaining for cytb5 was
      the most reliable marker for persistent androgenesis in ovaries with minimal
      primordial follicle numbers (<100) and residual stromal cells. Following
      ovariectomy, a significant decrease in testosterone (-27.7%, -30.8%, -27.5%; p <
      0.01) and androstenedione (-33.4%, -35.7%, -46.0%; p < 0.01) was observed in
      monkeys with low, intermediate, and high primordial follicle counts,
      respectively. CONCLUSIONS: Despite low follicle numbers, the aging macaque ovary
      retains the necessary proteins for androgenesis within residual stromal cells and
      contributes to peripheral androgen concentrations.

PMID- 21864138
TI  - Does an early onset and continuous chain of rehabilitation improve the long-term
      functional outcome of patients with severe traumatic brain injury?
AB  - There are currently no international guidelines regarding treatment in the early
      rehabilitation phase for persons with severe traumatic brain injury (TBI), and
      only a few studies have investigated the effect of integrating rehabilitation
      into acute TBI care. The aim of the study was to evaluate whether a continuous
      chain of rehabilitation that begins with the acute phase could improve the
      functional outcome of severe TBI patients, compared to a broken chain of
      rehabilitation that starts in the sub-acute phase of TBI. A total of 61 surviving
      patients with severe TBI were included in a quasi-experimental study conducted at
      the Level I trauma center in Eastern Norway. In the study, 31 patients were in
      the early rehabilitation group (Group A) and 30 patients were in the delayed
      rehabilitation group (Group B). The functional outcomes were assessed 12 months
      post-injury with the Glasgow Outcome Scale Extended (GOSE) and the Disability
      Rating Scale (DRS). A favorable outcome (GOSE 6-8) occurred in 71% of the
      patients from Group A versus 37% in Group B (p=0.007). The DRS score was
      significantly better in Group A (p=0.03). The ordinal logistic regression
      analysis was used to quantify the relationship between the type of rehabilitation
      chain and the GOSE. A better GOSE outcome was found in patients from Group A
      (unadjusted OR 3.25 and adjusted OR 2.78, respectively). These results support
      the hypothesis that better functional outcome occurs in patients who receive
      early onset and a continuous chain of rehabilitation.

PMID- 21864139
TI  - Bioavailability and toxicological potential of sunflower-bound residues of (14)C
      chlorpyrifos insecticide in rats.
AB  - Sunflower plants were treated with (14)C-chlorpyrifos under conditions simulating
      local agricultural practice. Residues present in the oil, methanol extract and
      cake of the treated sunflower seeds were 7.2, 2.8, and 12 ppm, respectively. When
      rats fed on sunflower cake containing bound residues for three days, the animals
      eliminated 46 % of the radioactivity in urine, 25 % in feces and 10 % in the
      expired air. A further bioavailable amount of 8 % was found in selected organs
      indicating that the bound residues were highly bioavailable. Chromatographic
      analysis of urine extract revealed the presence of the parent compound, its oxon,
      desethyl chlorpyrifos and desethyl chlorpyrifos oxon as free metabolites in
      addition to a conjugated metabolite. It was liberated by acid hydrolysis and
      identified as 3,5,6-trichloro-2-hydroxypyridine. Bound residues were found to
      have biological effects such as inhibition of rat plasma ChE, elevations of liver
      parameters (ALT, AST, and ALP), decrease in total protein and albumin content
      suggesting a hepatotoxic potential. A significant increase in the values of
      creatinine, urea, cholesterol, triglycerides and significant decrease in Catalase
      and Glutathion-S-Transfrase were observed in treated rats.

PMID- 21864140
TI  - Biodegradation of nicotine by a novel Strain Shinella sp. HZN1 isolated from
      activated sludge.
AB  - The nicotine-degrading bacterium HZN1 was isolated from activated sludge and
      identified as Shinella sp. based on its physiological characteristics and
      analysis of 16S rDNA gene. Strain HZN1 is capable of using nicotine as the sole
      carbon source in the mineral salts medium. The optimum temperature and pH for
      strain HZN1 growth and nicotine degradation were 30 degrees C and 7.0,
      respectively. It could degrade approximately 100 % of 0.5 g L(-1) of nicotine
      within 9 h. Three intermediate metabolites were produced by the strain HZN1 and
      identified as cotinine, myosmine and nicotyrine using gas chromatography-mass
      spectrometry. This is the first report of nicotine-degrading strain from the
      genus of Shinella. The results showed that strain HZN1 could be potentially
      employed in bioremediation of nicotine. Our findings would provide a new insight
      into the biodegradation of nicotine.

PMID- 21864141
TI  - Malathion-induced sublethal toxicity on the intestine of cricket frog (Fejervarya
      limnocharis).
AB  - The effect of malathion [diethyl(dimethoxythiophosphorylthio)succinate] at
      sublethal concentration (0.006 ppm) on intestinal parameters of cricket frog
      (Fejervarya limnocharis) was studied for 24 hrs to 240 hrs of exposure and
      remarkable histopathological alterations were observed. The study on intestinal
      parameters revealed acute pathological conditions in the intestinal wall. The
      toxic effect became evident as the cytoplasm of the cells disintegrated and the
      cells became empty and vacuolated. The cell membranes were also ruptured.
      Degenerative changes of the absorptive surface (villi) of the intestine in the
      different periods of exposure were pronounced. Severe atrophic nature (necrotic
      mucosa) of the intestine began from 48 hrs onwards to 96 hrs of exposure.

PMID- 21864142
TI  - Falling Man: encounters with catastrophic change.
AB  - The assault on the twin towers thrust Americans into an encounter with
      catastrophic change. Previously protected by the illusion of security fed by our
      relative imperviousness to others' points of view, we are harshly awakened to our
      defensive blindness. This rupture helps us see the particular beyond the seeming
      universality, locating culture as a variable frame defining meanings through the
      narratives that hold complexities of human experience in conceptual space. Don
      DeLillo's Falling Man offers a reading of catastrophe as a forced encounter with
      fallibility, breaking apart illusions of sameness and difference, towards
      integration of what trauma excludes from awareness.

PMID- 21864143
TI  - Racism in the consulting room: myth or reality?
AB  - This paper explores ways in which issues of race might impact on, and/or be
      ignored within, the practice of psychotherapy. Racial difference, that is being
      white as well as being black, taps into ingrained patterns of binary thinking
      that create hierarchies of "otherness." This generates anxiety which leads some
      therapists to avoid seeing race or naming its resonance in the therapeutic
      alliance. The origins of this splitting may lie in the unconscious, from whence
      it can be subtly nudged into more conscious awareness, as a seminal paper by
      Andrew Curry, published in this journal, suggested some forty-five years ago.
      Other modalities bring these dynamics more directly into the therapeutic space by
      exploring the patient's familial history or their daily lived experiences of
      racial (dis)advantage from an explicitly empowering standpoint. But whatever
      route is taken, racism is not an animal that can, or should, be left sleeping in
      the corner of the consulting room.

PMID- 21864144
TI  - Sadism linked to loneliness: psychodynamic dimensions of the sadistic serial
      killer Jeffrey Dahmer.
AB  - In this article the psychodynamic link between loneliness and sadism is examined
      on basis of a case report of the sadistic and cannibalistic serial killer Jeffery
      Dahmer. Envy, shame/rage mechanism, a disturbed oral-sadistic development,
      castration fear and severe feelings of inferiority, the conviction of being
      unlovable and unacceptable, need to diminish tension, powerful and sadistic
      fantasies as a consequence of inadequate and frustrated parenting, and reality
      distortion appear to be involved in sadistic etiology.

PMID- 21864145
TI  - Pronouns and progress: a psychoanalytic primer.
AB  - Psychoanalytic psychotherapists have the role responsibility to hover evenly over
      everything that is said--and not said--in the analytic situation. Pronouns may be
      worthy of special attention. Just as children demonstrate a predictable course in
      the acquisition and mastery of pronouns, it may be that the analytic patient also
      shows a predictable sequence in the deployment of pronouns over the course of a
      successful treatment. The analytic patient will move from a focus on "They," to
      joining the analyst in "We," before ultimately separating to become an "I." A
      third person focus in the opening phase, may, with familiarity, move to second
      person intimacy, ultimately yielding to first person agency. These grammatical
      markers occur in the opening, middle and termination/follow-up phases of a
      successful psychoanalytic treatment, during which the pre-morbid introjects are
      identified, chewed up, and, eventually nudged aside by the healthier therapeutic
      introject, from which a new or renewed identity may emerge. Analysis of the
      Grimm's fairy tale "The Wolf and the Kids" illustrations the importance of
      metabolizing old introjects.

PMID- 21864146
TI  - The alterability of the memory trace.
AB  - This essay is the result of a critical reading exercise of Freud's 1925 text Note
      upon the Mystic Writing-Pad. This reading led me to argue the necessity of
      radicalizing some consequences that emerge from the analogy established by Freud
      between the psychic apparatus, and a certain writing machine. The purpose of this
      paper is to compare critically such a model of the psychic apparatus and what
      Derrida describes as processes of inscriptionality. One of the most relevant
      consequences of this writing analogy is that those notions in psychoanalysis
      compromised with the idea of an origin -or that are treated as original in terms
      of the genesis of the psychic apparatus- cannot be further sustain as unaltered
      nucleus. Primal repression is one of the Freudian notions that operate anchored
      to these compromises.

PMID- 21864147
TI  - Toward a tripartite vision of supervision for psychoanalysis and psychoanalytic
      psychotherapies: alliance, transference-countertransference configuration, and
      real relationship.
AB  - The psychoanalytic supervision relationship is examined as a tripartite
      phenomenon, comprised of the supervisory alliance, transference
      countertransference configuration, and real relationship. While most supervisory
      analysts would readily acknowledge that a real (or personal) relationship element
      exists in analytic supervision, that facet of the supervision relationship has
      not routinely been incorporated into considerations of psychoanalytic
      supervision. In this vision of supervision, real relationship, supervisory
      alliance, and transference-countertransference configuration are presented as
      integral and complementary constructs that define psychoanalytic supervision.
      Each of those three components is examined briefly with regard to its beginnings,
      evolution, and contemporary status; each component is also considered from an
      empirical perspective. While we have a growing quantitative and qualitative
      research foundation that supports psychoanalytic practice, psychoanalytic
      supervision has largely been ignored as a subject and object of scientific study.
      Supervisory alliance, transference-countertransference configuration, and real
      relationship are explored as research ready variables. Some clinical hypotheses-
      eminently testable and worthy of investigation--are proposed with regard to each
      component of the model, and some ideas--albeit tentative and preliminary--about
      how to initiate such inquiries are offered.

PMID- 21864150
TI  - Faunistic composition, ecological properties and zoogeographical composition of
      the family Elateridae (Coleoptera) of the Central Anatolian region of Turkey.
AB  - The focus of this study was to understand the faunistic composition, ecological
      properties and zoogeographical composition of Elateridae (Coleoptera) of the
      Central Anatolian region. 72 species belonging to seven subfamilies and 25 genera
      were identified. The major part of the Elateridae fauna of the Central Anatolian
      region is formed by the subfamilies Elaterinae and Cardiophorinae. The genus
      Cardiophorus was the most species-rich genus. The species composition of the
      Elateridae fauna of the Central Anatolian region is partially consistent with
      known Elateridae fauna of Turkey. The Central Anatolian region shares most
      species with the European part of the Western Palaearctic as does the Elateridae
      fauna of Turkey. Detailed localities of nine species are given for the first time
      for Turkey, with emphasis on the Central Anatolian region.

PMID- 21864151
TI  - Female choice reveals terminal investment in male mealworm beetles, Tenebrio
      molitor, after a repeated activation of the immune system.
AB  - Increasing evidence suggests that secondary sexual traits reflect
      immunocompetence of males in many animal species. This study experimentally
      investigated whether a parasite-like immunological challenge via a nylon implant
      affects sexual attractiveness of males in Tenebrio molitor L. (Coleoptera:
      Tenebrionidae) Although a single immunological challenge significantly reduced
      sexual attractiveness and locomotor activity of males, it had no adverse effect
      on their survival. A second immune challenge of the same males increased their
      attractiveness. However, it was found that the repeated challenge significantly
      reduced locomotor activity of males and caused higher mortality. This result
      indicates terminal investment on sexual signaling, which is supposedly based on a
      trade-off between pheromone production and energy expenditures needed for such
      activities as recovery of immune system and locomotor activity. When the third
      implantation was carried out in the same group of males, melanization of nylon
      implants was found to be lower in more attractive than in less attractive males.
      This suggests that males that became sexually attractive after the second immune
      challenge did not invest in recovery of their immune system.

PMID- 21864152
TI  - Assessment of darkling beetle fauna after implementation of an environmental
      restoration program in the southern Iberian Peninsula affected by the Aznalcollar
      toxic spill.
AB  - This study is part of the Follow up Restoration Program of animal communities
      that colonize the Guadiamar River Basin. In 1998, the area was affected by a
      release of toxic sludge after the retention walls of the Aznalcollar Mines
      (southern Iberian Peninsula) broke. The main objective of this study was to
      assess the current state of the population of Tenebrionidae, one of the most
      representative groups of edaphic Coleoptera inhabiting the Guadiamar River Basin.
      This paper analyses the progress made by the darkling beetle community six years
      after the disaster occurred and the Restoration Program was implemented. The
      study is based on faunistic data from systematic sampling carried out for six
      years to monitor plots distributed across the damaged area. To make an overall
      assessment of the tenebrionid fauna in relation to adjacent areas qualitative and
      quantitative ecological indices were applied, and temporal follow up and
      biogeographical comparisons were also made. The results indicate that, on the
      whole, tenebrionid fauna was somewhat affected by the Aznalcollar Mine spill, and
      that a greater loss of fauna was detected closer to the accident site. The
      analysis of the temporal population dynamic suggests that the most affected zones
      are undergoing a process of re-colonization. However, this process varies widely
      by species and has not yet reached the expected levels of a non-affected river
      basin in the southern Iberian Peninsula.

PMID- 21864153
TI  - Utility of multi-gene loci for forensic species diagnosis of blowflies.
AB  - Contemporary studies in forensic entomology exhaustively evaluate gene sequences
      because these constitute the fastest and most accurate method of species
      identification. For this purpose single gene segments, cytochrome oxidase subunit
      I (COI) in particular, are commonly used. However, the limitation of such
      sequences in identification, especially of closely related species and
      populations, demand a multi-gene approach. But this raises the question of which
      group of genes can best fulfill the identification task? In this context the
      utility of five gene segments was explored among blowfly species from two
      distinct geographic regions, China and Pakistan. COI, cytochrome b (CYTB), NADH
      dehydrogenase 5 (ND5), nuclear internal transcribed spacers (ITS1 and ITS2), were
      sequenced for eight blowfly species including Chrysomya megacephala F. (Diptera:
      Calliphoidae), Ch. pinguis Walker, Lucilia sericata Meigen L. porphyrina Walker,
      L. illustris Meigen Hemipyrellia ligurriens Wiedemann, Aldrichina grahami
      Aldrich, and the housefly, Musca domestica L. (Muscidae), from Hangzhou, China;
      while COI, CYTB, and ITS2 were sequenced for four species, i.e. Ch. megacephala,
      Ch. rufifacies, L. cuprina, and the flesh fly, Sarcophaga albiceps Meigen
      (Sarcophagidae), from Dera Ismail Khan Pakistan. The results demonstrate a
      universal utility of these gene segments in the molecular identification of flies
      of forensic importance.

PMID- 21864154
TI  - Survey of leafhopper species in almond orchards infected with almond witches'
      broom phytoplasma in Lebanon.
AB  - Leafhoppers (Hemiptera: Auchenorrhyncha: Cicadellidae) account for more than 80%
      of all "Auchenorrhynchous" vectors that transmit phytoplasmas. The leafhopper
      populations in two almond witches'-broom phytoplasma (AlmWB) infected sites:
      Tanboureet (south of Lebanon) and Bourj El Yahoudieh (north of Lebanon) were
      surveyed using yellow sticky traps. The survey revealed that the most abundant
      species was Asymmetrasca decedens, which represented 82.4% of all the leafhoppers
      sampled. Potential phytoplasma vectors in members of the subfamilies Aphrodinae,
      Deltocephalinae, and Megophthalminae were present in very low numbers including:
      Aphrodes makarovi, Cicadulina bipunctella, Euscelidius mundus, Fieberiella
      macchiae, Allygus theryi, Circulifer haematoceps, Neoaliturus transversalis, and
      Megophthalmus scabripennis. Allygus theryi (Horvath) (Deltocephalinae) was
      reported for the first time in Lebanon. Nested PCR analysis and sequencing showed
      that Asymmetrasca decedens, Empoasca decipiens, Fieberiella macchiae, Euscelidius
      mundus, Thamnottetix seclusis, Balclutha sp., Lylatina inexpectata, Allygus sp.,
      and Annoplotettix danutae were nine potential carriers of AlmWB phytoplasma.
      Although the detection of phytoplasmas in an insect does not prove a definite
      vector relationship, the technique is useful in narrowing the search for
      potential vectors. The importance of this information for management of AlmWB is
      discussed.

PMID- 21864155
TI  - Impact of insecticides on parasitoids of the leafminer, Liriomyza trifolii, in
      pepper in south Texas.
AB  - Liriomyza leafminers (Diptera: Agromyzidae) are cosmopolitan, polyphagous pests
      of horticultural plants and many are resistant to insecticides. Producers in
      South Texas rely on insecticides as the primary management tool for leafminers,
      and several compounds are available. The objective of this study is to address
      the efficacy of these compounds for controlling Liriomyza while minimizing their
      effects against natural enemies. Research plots were established at Texas
      AgriLife research center at Weslaco, Texas in fall 2007 and spring 2008 seasons,
      and peppers were used as a model crop. Plots were sprayed with novaluron,
      abamectin, spinetoram, lambda-cyhalothrin and water as treatments according to
      leafminer infestation; insecticide efficacy was monitored by collecting leaves
      and infested foliage. Plant phenology was also monitored. Novaluron was the most
      effective insecticide and lambda-cyhalothrin showed resurgence in leafminer
      density in fall 2007 and no reduction in spring 2008. Other compounds varied in
      efficacy. Novaluron showed the least number of parasitoids per leafminer larva
      and the lowest parasitoid diversity index among treatments followed by
      spinetoram. Liriomyza trifolii (Burgess) was the sole leafminer species on
      peppers, and 19 parasitoid species were found associated with this leafminer.
      Application of these insecticides for management of leafminers with conservation
      of natural enemies is discussed.

PMID- 21864157
TI  - How dietary phosphorus availability during development influences condition and
      life history traits of the cricket, Acheta domesticas.
AB  - Phosphorus is extremely limited in the environment, often being 10-20 times lower
      in plants than what invertebrate herbivores require. This mismatch between
      resource availability and resource need can profoundly influence herbivore life
      history traits and fitness. This study investigated how dietary phosphorus
      availability influenced invertebrate growth, development time, consumption,
      condition, and lifespan using juvenile European house crickets, Acheta domesticus
      L. (Orthoptera: Gryllidae). Crickets reared on high phosphorus diets ate more
      food, gained more weight, were in better condition at maturity, and contained
      more phosphorus, nitrogen, and carbon in their bodies at death than crickets
      reared on low phosphorus diets. There was also a trend for crickets reared on
      high phosphorus diets to become larger adults (interaction with weight prior to
      the start of the experiment). These findings can be added to the small but
      growing number of studies that reveal the importance of phosphorus to insect life
      history traits. Future research should explore the importance of dietary
      phosphorus availability relative to protein, lipid, and carbohydrate
      availability.

PMID- 21864158
TI  - Distinguishing male and female Chinese rose beetles, Adoretus sinicus, with an
      overview of Adoretus species of biosecurity concern.
AB  - The Chinese rose beetle, Adoretus sinicus Burmeister (Coleoptera: Scarabaeidae:
      Rutelinae: Adoretini), is a broadly polyphagous scarab beetle that is
      economically important and causes damage to a wide variety of host plants
      including agricultural crops and ornamentals in Southeast Asia, China, the
      Hawaiian Islands and several other Pacific Islands. The species has become
      established in numerous regions and is of biosecurity concern because importation
      of this species to other regions poses a threat to agriculture due to its
      generalist herbivore feeding habits. Field and laboratory research directed
      towards control of the species is hampered by the lack of characteristics that
      allow accurate determination of the sexes on live beetles in the field. Here,
      three recognizable and reliable non-destructive morphological differences between
      the sexes of A. sinicus are documented: (1) the form of the terminal sternite;
      (2) the length to width ratio of protarsomere 1, and; 3) the ratio of the
      combined length of protarsomeres 2-4 to the length of protarsomere 1. Because
      many Adoretus species are of biosecurity concern, and because tools to identify
      Adoretus species are lacking, we review the natural history and research on
      control associated with A. sinicus as well as the genus as a whole.

PMID- 21864156
TI  - A review of chemosensation and related behavior in aquatic insects.
AB  - Insects that are secondarily adapted to aquatic environments are able to sense
      odors from a diverse array of sources. The antenna of these insects, as in all
      insects, is the main chemosensory structure and its input to the brain allows for
      integration of sensory information that ultimately ends in behavioral responses.
      Only a fraction of the aquatic insect orders have been studied with respect to
      their sensory biology and most of the work has centered either on the description
      of the different types of sensilla, or on the behavior of the insect as a whole.
      In this paper, the literature is exhaustively reviewed and ways in which antennal
      morphology, brain structure, and associated behavior can advance better
      understanding of the neurobiology involved in processing of chemosensory
      information are discussed. Moreover, the importance of studying such group of
      insects is stated, and at the same time it is shown that many interesting
      questions regarding olfactory processing can be addressed by looking into the
      changes that aquatic insects undergo when leaving their aquatic environment.

PMID- 21864159
TI  - Butterfly larval host plant use in a tropical urban context: life history
      associations, herbivory, and landscape factors.
AB  - This study examines butterfly larval host plants, herbivory and related life
      history attributes within Nagpur City, India. The larval host plants of 120
      butterfly species are identified and their host specificity, life form, biotope,
      abundance and perennation recorded; of the 126 larval host plants, most are trees
      (49), with fewer herbs (43), shrubs (22), climbers (7) and stem parasites (2).
      They include 89 wild, 23 cultivated, 11 wild/cultivated and 3 exotic plant
      species; 78 are perennials, 43 annuals and 5 biannuals. Plants belonging to
      Poaceae and Fabaceae are most widely used by butterfly larvae. In addition to
      distinctions in host plant family affiliation, a number of significant
      differences between butterfly families have been identified in host use patterns:
      for life forms, biotopes, landforms, perennation, host specificity, egg batch
      size and ant associations. These differences arising from the development of a
      butterfly resource database have important implications for conserving butterfly
      species within the city area. Differences in overall butterfly population sizes
      within the city relate mainly to the number of host plants used, but other
      influences, including egg batch size and host specificity are identified. Much of
      the variation in population size is unaccounted for and points to the need to
      investigate larval host plant life history and strategies as population size is
      not simply dependent on host plant abundance.

PMID- 21864160
TI  - Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid
      arthritis.
AB  - Interleukin-18 (IL-18) is a highly regulated inflammatory cytokine that is
      elevated in synovial tissues and synovial fluids of patients with rheumatoid
      arthritis (RA) compared with patients with osteoarthritis (OA) and patients with
      other arthropathies. Within the RA joint, IL-18 can contribute to the
      inflammatory process by inducing leukocyte extravasation through upregulation of
      endothelial cell adhesion molecules, the release of chemokines from RA synovial
      fibroblasts, and directly as a monocytes, lymphocyte, and neutrophil
      chemoattractant. IL-18 can also help maintain and develop the inflammatory pannus
      by inducing endothelial cell migration and angiogenesis. IL-18 does this directly
      by binding and activating endothelial cells and indirectly by inducing RA
      synovial fibroblasts to produce angiogenic chemokines and vascular endothelial
      growth factor. IL-18 is present in RA synovial fluid in high levels, where it
      functions as an angiogenic mediator and leukocyte chemoattractant. IL-18 mediates
      all these inflammatory processes by binding to its receptor, IL-18 receptor, and
      initiating the activation of different signaling cascades leading to changes in
      target cells gene expression and behavior. IL-18 has been identified as a
      potential therapeutic target in the treatment of RA.

PMID- 21864162
TI  - Opportunities and challenges for episode-based payment.

PMID- 21864161
TI  - Human amniotic fluid stem cells seeded in fibroin scaffold produce in vivo
      mineralized matrix.
AB  - This study investigated the potential of amniotic fluid stem cells (AFSCs) to
      synthesize mineralized extracellular matrix (ECM) within different porous
      scaffolds of collagen, poly-D,L-lactic acid (PDLLA), and silk fibroin. The AFSCs
      were initially differentiated by using an osteogenic medium in two-dimensional
      culture, and expression of specific bone proteins and the physiologic mineral
      production by the AFSCs were analyzed. In particular, during differentiation
      process, AFSCs expressed proteins like Runt-related transcription factor 2
      (Runx2), Osterix, Osteopontin, and Osteocalcin with a sequential expression,
      analogous to those occurring during osteoblast differentiation, and produced
      extracellular calcium stores. AFSCs were then cultured on three-dimensional (3D)
      scaffolds and evaluated for their ability to differentiate into osteoblastic
      cells in vivo. Stem cells were cultured in vitro for 1 week in collagen, fibroin,
      and PDLLA scaffolds. The effect of predifferentiation of the stem cells in
      scaffolds on the subsequent bone formation in vivo was determined in a rat
      subcutaneous model. With the addition of a third dimension, osteogenic
      differentiation and mineralized ECM production by AFSCs were significantly
      higher. This study demonstrated the strong potential of AFSCs to produce 3D
      mineralized bioengineered constructs in vivo and suggests that fibroin may be an
      effective scaffold material for functional repair of critical size bone defects.

PMID- 21864163
TI  - Images in clinical medicine. Pneumatosis cystoides intestinalis.

PMID- 21864164
TI  - Clinical decisions. Treatment of a 6-year-old girl with vesicoureteral reflux-
      polling results.

PMID- 21864165
TI  - HIV surveillance, public health, and clinical medicine--will the walls come
      tumbling down?

PMID- 21864168
TI  - Images in clinical medicine. Balo's concentric sclerosis.

PMID- 21864167
TI  - Thrombopoietin-receptor agonists for primary immune thrombocytopenia.

PMID- 21864170
TI  - Preventing exacerbations of COPD--advice from Hippocrates.

PMID- 21864169
TI  - Case records of the Massachusetts General Hospital. Case 26-2011. A 7-year-old
      boy with a complex cyst in the kidney.

PMID- 21864171
TI  - Systemic lupus erythematosus and the neutrophil.

PMID- 21864166
TI  - Azithromycin for prevention of exacerbations of COPD.
AB  - BACKGROUND: Acute exacerbations adversely affect patients with chronic
      obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with
      a variety of inflammatory airway diseases. METHODS: We performed a randomized
      trial to determine whether azithromycin decreased the frequency of exacerbations
      in participants with COPD who had an increased risk of exacerbations but no
      hearing impairment, resting tachycardia, or apparent risk of prolongation of the
      corrected QT interval. RESULTS: A total of 1577 subjects were screened; 1142
      (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily
      (570 participants), or placebo (572 participants) for 1 year in addition to their
      usual care. The rate of 1-year follow-up was 89% in the azithromycin group and
      90% in the placebo group. The median time to the first exacerbation was 266 days
      (95% confidence interval [CI], 227 to 313) among participants receiving
      azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants
      receiving placebo (P<0.001). The frequency of exacerbations was 1.48
      exacerbations per patient-year in the azithromycin group, as compared with 1.83
      per patient-year in the placebo group (P=0.01), and the hazard ratio for having
      an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73
      (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory
      Questionnaire (on a scale of 0 to 100, with lower scores indicating better
      functioning) improved more in the azithromycin group than in the placebo group (a
      mean [+/-SD] decrease of 2.8+/-12.8 vs. 0.6+/-11.4, P=0.004); the percentage of
      participants with more than the minimal clinically important difference of -4
      units was 43% in the azithromycin group, as compared with 36% in the placebo
      group (P=0.03). Hearing decrements were more common in the azithromycin group
      than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS: Among selected
      subjects with COPD, azithromycin taken daily for 1 year, when added to usual
      treatment, decreased the frequency of exacerbations and improved quality of life
      but caused hearing decrements in a small percentage of subjects. Although this
      intervention could change microbial resistance patterns, the effect of this
      change is not known. (Funded by the National Institutes of Health;
      ClinicalTrials.gov number, NCT00325897.).

PMID- 21864172
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864173
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864174
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864175
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864176
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864177
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864178
TI  - Transmission of resistant bacteria in intensive care.

PMID- 21864180
TI  - Abiraterone and increased survival in metastatic prostate cancer.

PMID- 21864181
TI  - Abiraterone and increased survival in metastatic prostate cancer.

PMID- 21864182
TI  - Abiraterone and increased survival in metastatic prostate cancer.

PMID- 21864184
TI  - FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

PMID- 21864186
TI  - Selenium and the course of mild Graves' orbitopathy.

PMID- 21864187
TI  - Selenium and the course of mild Graves' orbitopathy.

PMID- 21864189
TI  - gp100 peptide vaccine in melanoma.

PMID- 21864191
TI  - Childhood diarrhea deaths after rotavirus vaccination in Mexico.

PMID- 21864195
TI  - Heterochromatin patterns and ribosomal DNA loci distribution in diploid and
      polyploid Crotalaria species (Leguminosae, Papilionoideae), and inferences on
      karyotype evolution.
AB  - Most Crotalaria species display a symmetric karyotype with 2n = 16, but 2n = 14
      is found in Chrysocalycinae subsection Incanae and 2n = 32 in American species of
      the section Calycinae. Seven species of the sections Chrysocalycinae, Calycinae,
      and Crotalaria were analyzed for the identification of heterochromatin types with
      GC- and AT-specific fluorochromes and chromosomal location of ribosomal DNA loci
      using fluorescent in situ hybridization (FISH). A major 45S rDNA locus was
      observed on chromosome 1 in all the species, and a variable number of minor ones
      were revealed. Only one 5S rDNA locus was observed in the species investigated.
      Chromomycin A(3) (CMA) revealed CMA(+) bands colocalized with most rDNA loci,
      small bands unrelated to ribosomal DNA on two chromosome pairs in Crotalaria
      incana, and CMA(+) centromeric bands that were quenched by distamycin A were
      detected in species of Calycinae and Crotalaria sections. DAPI(+) bands were
      detected in C. incana. The results support the species relationships based on
      flower specialization and were useful for providing insight into mechanisms of
      karyotype evolution. The heterochromatin types revealed by fluorochromes suggest
      the occurrence of rearrangements in repetitive DNA families in these
      heterochromatic blocks during species diversification. This DNA sequence turnover
      and the variability in number/position of rDNA sites could be interpreted as
      resulting from unequal crossing over and (or) transposition events. The
      occurrence of only one 5S rDNA locus and the smaller chromosome size in the
      polyploids suggest that DNA sequence losses took place following polyploidization
      events.

PMID- 21864196
TI  - Reporter gene HEK 293 cells and WNT/Frizzled fusion proteins as tools to study
      WNT signaling pathways.
AB  - WNT/Frizzled receptor (FZD) signaling pathways are pivotal for physiological and
      pathophysiological processes. In humans, the complexity of WNT/FZD signaling is
      based on 19 WNTs, 10 FZDs and at least two (co)receptors (LRP5/6) mediating
      supposably four different signaling cascades. The detailed investigation of the
      specific function of the different initiating components is primarily hampered by
      the lack of most WNT proteins in a purified form. Therefore, we constructed and
      examined a chimeric protein of WNT3a and FZD4 as a suitable approach to overcome
      this obstacle for future studies of the specificity of other WNT/FZD
      combinations. Furthermore, we produced four different reporter HEK 293 cell lines
      to quantify the induced activation of the proposed signaling cascades, the beta
      catenin-, the NFAT-, the AP-1- and the CRE-regulated pathways. The chimera
      WNT3aFZD4 efficiently induced beta-catenin-mediated luciferase activity. This
      activity was increased 40-fold compared with basal when LRP6 was stably
      cotransfected, proving that the chimera WNT3aFZD4 can also interact efficiently
      with LRP6. Our results demonstrate that the approach of using reporter gene cell
      lines in combination with WNT/FZD chimeras is efficient to study the beta-catenin
      mediated pathway and should also allow clarifying the specificity of WNT/FZD
      combinations in the activation of the other pathways.

PMID- 21864197
TI  - Risky decision-making in older adults without cognitive deficits: an fMRI study
      of VMPFC using the Iowa Gambling Task.
AB  - Some older adults without neurological disease exhibit impaired decision-making
      in risky, nontransparent situations, like the Iowa Gambling Task (IGT). The
      prefrontal cortices are particularly vulnerable to age-related decline, and
      numerous studies implicate the ventromedial prefrontal cortex (VMPFC) in
      successful IGT performance. However, the relationship between IGT performance and
      VMPFC function in older adults has not yet been tested by fMRI. In the present
      study, older adults with seemingly no cognitive impairments performed the IGT and
      a non-gambling control task during fMRI. Group analyses indicate that in these
      older adults, regardless of IGT performance level, a right VMPFC subregion is
      activated during the IGT, while successful IGT performance is correlated with
      left VMPFC activation, suggesting that bilateral VMPFC during risky,
      nontransparent situations may contribute to successful decision-making in older
      adults. Individual subject analyses reveal substantial variation regarding the
      extent and location of VMPFC activation during the IGT, a finding not captured in
      the group analysis: There is no correlation between IGT performance and extent of
      activation in the right VMPFC, although there is such a correlation between left
      VMPFC activation and IGT performance.

PMID- 21864198
TI  - Ameliorating spatial neglect with non-invasive brain stimulation: from
      pathophysiological concepts to novel treatment strategies.
AB  - Neglect is a multifaceted, complex syndrome, in which patients fail to detect or
      respond to stimuli or parts thereof located contralesionally. Non-invasive brain
      stimulation by means of transcranial magnetic stimulation (TMS) or transcranial
      direct current stimulation (tDCS) may not only be useful as diagnostic research
      tools to explore the pathophysiology of neglect, but also for ameliorating its
      symptoms. Current approaches for modulating neglect non-invasively are mainly
      based on the neurophysiological concept of interhemispheric inhibition, which
      suggests a pathological overactivation of the contralesional hemisphere due to
      reduced inhibitory influences from the lesioned one. Within this framework, non
      invasive brain stimulation mainly aims to inhibit the contralesional hemisphere
      to allow for rebalancing the system. However, facilitatory protocols for
      enhancing the ipsilesional neural circuitry might also prove useful. In this
      review, we discuss the contribution of non-invasive brain stimulation to current
      pathological concepts of neglect, the promising results of the proof-of-principle
      studies currently available as well as the specific aspects to be systematically
      investigated before broader clinical trials may eventually suggest a routine
      clinical application.

PMID- 21864199
TI  - Singing proficiency in congenital amusia: imitation helps.
AB  - Singing out of tune characterizes congenital amusia. Here, we examine whether an
      aid to memory improves singing by studying vocal imitation in 11 amusic adults
      and 11 matched controls. Participants sang a highly familiar melody on the
      original lyrics and on the syllable /la/ in three conditions. First, they sang
      the melody from memory. Second, they sang it after hearing a model, and third,
      they sang in unison with the model. Results show that amusic individuals benefit
      from singing by imitation, whether singing after the model or in unison with the
      model. The amusics who were the most impaired in memory benefited most,
      particularly when singing on the syllable /la/. Nevertheless, singing remains
      poor on the pitch dimension; rhythm was intact and unaffected by imitation. These
      results point to memory as a source of impairment in poor singing, and to
      imitation as a possible aid for poor singers.

PMID- 21864200
TI  - Lexical competition for production in a case of nonfluent aphasia: converging
      evidence from four different tasks.
AB  - We report an individual with Broca's aphasia (J.H.M.), who exhibited powerful
      lexical context effects in word production tasks. In an adjective-noun production
      task (Experiment 1), J.H.M.'s production accuracy decreased as the number of
      adjectives in the phrase increased (e.g., curly hair vs. long curly hair). In a
      picture pair naming task (Experiment 2), J.H.M.'s naming accuracy was high, but
      her naming latencies were abnormally delayed when pairs were semantically related
      (e.g., goat and pig). This pattern was not observed for older controls. In a
      computerized Stroop task (Experiment 3), J.H.M.'s naming latencies were
      abnormally prolonged in the conflict condition, relative to a baseline colour
      naming task. This effect was far in excess of that for controls. Finally, in a
      blocked cyclic naming task (Experiment 4), J.H.M.'s accuracy was poorer and her
      latencies slower when the pictures were semantically related than when they were
      unrelated, and this effect built up across successive presentation cycles. It was
      far in excess of that exhibited by older controls. We propose that J.H.M.'s
      pattern of impairment across these four very different tasks suggests an
      impairment to a lexical control mechanism, whose normal function is to modulate
      the flow of activation throughout the lexical network, so as to minimize the
      competitive effects of nontarget lexical items.

PMID- 21864201
TI  - Unusual evolution in Wegener's granulomatosis: recovery of pulmonary involvement
      while renal disease progressed to end-stage.
AB  - A 54-year-old male patient was admitted for acute respiratory distress with
      fever. He was suffering from chronic sinusitis/rhinitis and had persistent otitis
      for the past 2 months before admission despite several antibiotics courses. He
      developed a complex pulmonary involvement (embolism and diffuse alveolar
      hemorrhage) with acute glomerular disease (proteinuria and hematuria but
      initially no renal failure). Clinical suspicion of Wegener's granulomatosis was
      confirmed by the positive high titer of antineutrophil cytoplasmic antibodies (c
      ANCA with antiproteinase 3 specificity) and despite a negative nasal biopsy.
      Treatment including cyclophosphamide and methylprednisolone intravenous pulses
      permitted pulmonary recovery over 4 weeks contrasting with the development of
      rapidly progressive glomerulonephritis and polyneuropathy of lower limbs. Renal
      biopsy showed pauci-immune crescentic and necrotizing glomerulonephritis.
      However, despite additional plasma exchanges, acute kidney injury worsened and
      the patient ended up in dialysis. Such a dissociated evolution was unexpected in
      this case since pulmonary and renal involvements reflected the same pathological
      process (small vessels vasculitis/capillaritis) and the same pathogenic mechanism
      (antiproteinase 3 autoantibodies).

PMID- 21864202
TI  - Preclinical pharmacokinetics of the radiomitigator KZ-41 in rats.
AB  - KZ-41, a quinic acid derivative, significantly reduces mortality in a murine
      model of hematopoietic acute radiation syndrome. The purpose of this study was to
      evaluate the systemic pharmacokinetics, elimination, and oral bioavailability of
      KZ-41 in rats. Male Sprague-Dawley rats (n = 6 per group) received a single dose
      (10 mg/kg) of KZ-41 administered either intravenously via the jugular vein or
      orally via gavage. In vitro stability was determined using both rat liver
      microsomes and the bacteria Gluconobacter oxydans. KZ-41 concentrations were
      determined using LC-MS/MS (liquid chromatography tandom mass spectrometry). Half
      life of KZ-41 was ~3 hr after either intravenous or oral administration. Mean
      volume of distribution was 3.3 L/kg. Extent of absorption (F) after oral
      administration was estimated to be ~100%, which was consistent with the finding
      that KZ-41 was stable to liver microsomal and bacterial degradation. Following
      intravenous administration, KZ-41 demonstrated a medium clearance and volume of
      distribution with a terminal half-life of ~3 hr. KZ-41 was rapidly and completely
      absorbed (F ? 1), which was consistent with the findings that KZ-41 is resistant
      to presystemic elimination mechanisms (i.e. enteric bacterial degradation and
      hepatic metabolism). Thus, KZ-41 represents an excellent candidate for further
      development as an orally available agent for the mitigation of radiation injury.

PMID- 21864203
TI  - Preclinical assessment of novel BRAF inhibitors: integrating pharmacokinetic
      pharmacodynamic modelling in the drug discovery process.
AB  - The objective of these studies were to determine the preclinical disposition of
      the two BRAF inhibitors, G-F and G-C, followed by pharmacokinetic (PK)
      pharmacodynamic (PD) modelling to characterize the concentration-efficacy
      relationship of these compounds in the Colo205 mouse xenograft model. With G-F,
      the relationship of pERK inhibition to concentration was also characterized.
      Compounds G-F and G-C were administered to mice, rats and dogs and the
      pharmacokinetics of G-F and G-C was determined. In addition, using indirect
      response models the concentration-efficacy relationship was described. The
      clearance of G-F was low; 0.625 and 4.65 mL/min/kg in rat and dog respectively.
      Similarly, the clearance of G-C was low in rat and dog, 0.490 and 4.43 mL/min/kg,
      respectively. Both compounds displayed low volumes of distribution (0.140-0.267
      L/kg), resulting in moderate half-lives across species (~2.5 to 4 h).
      Bioavailability was formulation dependent and decreased with increasing dose.
      Using the indirect response models, the KC(50) (50% K(max); maximal response)
      value for tumor growth inhibition for G-F and G-C were 84.5 and 19.2 MUM,
      respectively. The IC(50) for pERK inhibition in Colo205 tumors by G-F was
      estimated to be 29.2 MUM. High exposures of G-F and G-C were required for
      efficacy. Despite good PK properties of low CL and moderate half-life,
      limitations in obtaining exposures adequate for safety testing in rat and dog
      resulted in development challenges.

PMID- 21864204
TI  - Avoidant coping in panic disorder: a yohimbine biological challenge study.
AB  - Few studies have addressed whether the use of avoidance-oriented coping
      strategies is related to the development of panic in patients with panic
      disorder(PD). Self-report, clinician-rated, and physiological data were collected
      from 42 individuals who participated in a yohimbine biological challenge study,
      performed under double-blind, placebo-controlled conditions. Participants
      included 20 healthy controls and 22 currently symptomatic patients who met DSM-IV
      TR diagnostic criteria for PD. Consistent with prediction, patients with PD who
      had higher perceived efficacy of avoidance-oriented strategies in reducing
      anxiety-related thoughts reported increased severity in panic symptoms during the
      yohimbine challenge condition as compared to the placebo. Further, patients with
      PD who had more fear of cognitive dyscontrol, cardiovascular symptoms, and
      publicly observable anxiety also reported increased severity in panic symptoms
      during the challenge. Healthy controls who had more fear of cardiovascular
      symptoms similarly reported increased severity in panic symptoms during the
      challenge. No effects were found for heart rate response to the challenge agent.
      These results provide support for the role of avoidance-oriented coping
      strategies and fear of anxiety-related symptoms as risk and maintenance factors
      in the development of panic symptoms, particularly within a biological challenge
      model.

PMID- 21864205
TI  - Telerehabilitation using virtual reality task can improve balance in patients
      with stroke.
AB  - PURPOSE: The objective of the telerehabilitation is a continuation of the
      rehabilitation process on patients' home. The study also compares the balance
      training in clinical environment with the telerehabilitation approach when the
      physiotherapists and physicians can follow the progress remotely. METHOD: In this
      paper, the preliminary study of the pilot project with virtual reality (VR)-based
      tasks for dynamic standing frame supported balance training is presented. Six
      patients with stroke participated in the study. The patients performed the
      balance training 3 weeks, 2 weeks in the clinical settings and 1 week in the home
      environment, five times a week, and each time for up to 20 minutes. Objective
      effectiveness was demonstrated by parameters as track time, number of collisions
      and the clinical instruments Berg Balance Scale (BBS), Timed Up & Go (TUG), 10-m
      walk test and standing on the unaffected and affected extremity. The outcomes
      were compared to the balance training group without VR and telerehabilitation
      support. A 2-way ANOVA was used to explore the differences between the both
      stroke groups. RESULTS: In patients who were subject to VR supported balance
      training, the BBS demonstrated improvement for 15%, the TUG for 29%, the 10-m
      walk for 26%, stance time on the affected and unaffected extremity for 200 and
      67%, respectively. The follow-up demonstrated that the patients preserved the
      gained functional improvement. The VR task performance time and number of
      collisions decreased to 45 and 68%, respectively. Besides, no statistical
      differences were found between the telerehabilitation approach with VR supported
      balance training and conventional balance training in clinical settings either
      regarding the overall mean level or regarding the mean improvement. CONCLUSIONS:
      The telerehabilitation approach in VR supported balance training improved balance
      in stroke patients and had similar effect on patients' postural functional
      improvement as conventional balance training in clinical settings. However, when
      balance training is continued on patient's home instead of the hospital, it would
      eventually decrease the number of outpatients' visits, reduce related costs and
      enable treatment of larger number of patients.

PMID- 21864206
TI  - Relationship between processed total motile sperm count of husband or donor semen
      and pregnancy outcome following intrauterine insemination.
AB  - We retrospectively analyzed 6,360 artificial insemination cycles of husband's
      semen through intrauterine insemination (AIH-IUI) or artificial insemination with
      donor semen through intrauterine insemination (AID-IUI) in patients with
      infertility between August, 1998 and August, 2010. The relationship between
      processed total motile sperm count (PTMS) and pregnancy outcome was determined.
      The study was divided into 6 groups according to PTMS. Group 1: <= 2.0 million,
      Group 2: 2.1-4.0 million, Group 3: 4.1-6.0 million, Group 4: 6.1-8.0 million,
      Group 5: 8.1-10.0 million, and Group 6: >10.0 million. There was no statistically
      significant difference in age, duration of infertility, unilateral tubal patency,
      induced ovulation, and single IUI or double IUI between the 6 groups in both AIH
      IUI and AID-IUI. The total clinical pregnancy rate of AIH-IUI was 10.81 % and AID
      IUI was 27.52 %. Among the 6 groups, the clinical pregnancy rate was the lowest
      in Group 1 (P < 0.05) in both AIH-IUI and AID-IUI. With the increased PTMS, the
      clinical pregnancy rate of IUI was improved. However, a statistical difference
      between groups was only observed for Group 1. When PTMS is <= 2 * 10(6) the
      clinical pregnancy rate of IUI is significantly decreased. In this case in vitro
      fertilization (IVF) should be adopted.

PMID- 21864207
TI  - Outcomes from switching from rotigotine patch to alternate therapies in
      Parkinson's disease.
AB  - BACKGROUND: When rotigotine patch was withdrawn from the US market, we
      prospectively gathered data on efficacy, side effects, and daytime sedation on
      patients while taking rotigotine and following the switch to alternate therapies.
      METHODS: Patients rated the efficacy of rotigotine on a scale of 0-5 (ineffective
      to extremely effective) and completed the Epworth Sleepiness Scale. At a follow
      up visit a mean of 3 months later, patients rated their change in efficacy and
      side effects on a scale of -3 to +3 (much worse to much better) and again
      completed the Epworth Sleepiness Scale. RESULTS: Thirty-three patients were
      switched to a single alternate treatment. On rotigotine, the average efficacy
      score was 3.5, and after switching, the average change in efficacy was -0.67
      (worsening). Average change scores for efficacy and adverse effects were 0.25 and
      0.38 for levodopa, -0.88 and -0.25 for ropinirole IR, -1.2 and -0.83 for
      ropinirole XL, -0.80 and 1.0 for pramipexole, and -1.0 and 0.50 for rasagiline,
      respectively. Average change in Epworth score on each alternate agent was -3.9, 
      2.3, 1.3, 3.0, and 1. CONCLUSION: Rotigotine was an effective treatment with all
      groups deteriorating after switch except for the levodopa group. Fifty-eight
      percent of patients preferred rotigotine versus 36% preferring the alternate
      treatment.

PMID- 21864208
TI  - Plasma symmetric dimethylarginine reference limits from the Framingham offspring
      cohort.
AB  - BACKGROUND: Symmetric dimethylarginine (SDMA) is a by-product of protein
      methylation. Once released from proteins, SDMA is eliminated by the kidneys;
      consequently, plasma concentration has been suggested as a sensitive marker of
      renal function. Furthermore, recent work implicates SDMA in the pathogenesis of
      cardiovascular disease. To date, reference limits for SDMA plasma concentrations
      in healthy individuals are lacking. METHODS: This study defined reference limits
      for plasma SDMA concentrations in 840 relatively healthy individuals of the
      Offspring Cohort from Framingham Heart Study (mean age 56 years, 61% women).
      Plasma SDMA concentrations were determined by LC-MS/MS using a stable isotope
      dilution assay. RESULTS: The median SDMA concentration in the reference sample
      was 0.37 MUmol/L (Q1, Q3:0.32, 0.43 MUmol/L) and the reference limits were 0.225
      and 0.533 (2.5th and 97.5th percentile). In a multivariable regression model,
      serum creatinine, age and total homocysteine were positively associated with SDMA
      (p<0.001 for all), whereas the body mass index and diastolic blood pressure were
      inversely related to SDMA (p-values<0.01 and 0.03, respectively). CONCLUSIONS:
      This study reports plasma SDMA reference limits from the community-based
      Framingham Heart Study. Plasma SDMA concentration was related positively to
      advancing age, but inversely to renal function. These reference limits may allow
      the identification of individuals with raised plasma SDMA concentrations.

PMID- 21864209
TI  - Sterol profiles in plasma and erythrocyte membranes in patients with Smith-Lemli
      Opitz syndrome: a six-year experience.
AB  - BACKGROUND: This study reports our experience over the last six years in the
      diagnosis of Smith-Lemli-Opitz syndrome and other inborn errors of cholesterol
      biosynthesis. METHODS: Gas chromatography/mass spectrometry was used to obtain
      sterol profiles in plasma and erythrocyte membranes of suspected patients.
      RESULTS: Plasma sterol reference values calculated in unaffected subjects (n=276)
      were in agreement with those previously reported. Among patients investigated
      from 2005 to 2010, we report 16 patients affected by Smith-Lemli-Opitz syndrome,
      three of whom represent new cases and 13 of whom were follow-up patients. In this
      period we also identified a new case of chondrodysplasia punctata 2 X-linked. The
      estimated incidence obtained for Smith-Lemli-Opitz syndrome was 1:93 suspected
      patients (1.08%). We also studied the effect of storage on the
      dehydrocholesterols/cholesterol ratio in plasma and erythrocyte membranes of
      patients affected by Smith-Lemli-Opitz syndrome stored at -20 degrees C for up to
      22 and 20 months, respectively. A significant negative linear correlation between
      storage time and the dehydrocholesterols/cholesterol ratio was identified in both
      plasma and erythrocyte membranes. The decrease in the
      dehydrocholesterols/cholesterol ratio in erythrocyte membranes was at least two
      fold higher than in plasma. CONCLUSIONS: The results of this study may be helpful
      for diagnosis and interpretation of data in patients with findings suggestive of
      a cholesterol biosynthesis defect.

PMID- 21864210
TI  - The development of marine biofilms on two commercial non-biocidal coatings: a
      comparison between silicone and fluoropolymer technologies.
AB  - The antimicrobial performance of two fouling-release coating systems, Intersleek
      700(r) (IS700; silicone technology), Intersleek 900(r) (IS900; fluoropolymer
      technology) and a tie coat (TC, control surface) was investigated in a short term
      (10 days) field experiment conducted at a depth of ca 0.5 m in the Marina Bandar
      Rawdha (Muscat, Oman). Microfouling on coated glass slides was analyzed using
      epifluorescence microscopy and adenosine-5'-triphosphate (ATP) luminometry. All
      the coatings developed biofilms composed of heterotrophic bacteria,
      cyanobacteria, seven species of diatoms (2 species of Navicula, Cylindrotheca
      sp., Nitzschia sp., Amphora sp., Diploneis sp., and Bacillaria sp.) and algal
      spores (Ulva sp.). IS900 had significantly thinner biofilms with fewer diatom
      species, no algal spores and the least number of bacteria in comparison with
      IS700 and the TC. The ATP readings did not correspond to the numbers of bacteria
      and diatoms in the biofilms. The density of diatoms was negatively correlated
      with the density of the bacteria in biofilms on the IS900 coating, and,
      conversely, diatom density was positively correlated in biofilms on the TC. The
      higher antifouling efficacy of IS900 over IS700 may lead to lower roughness and
      thus lower fuel consumption for those vessels that utilise the IS900 fouling
      release coating.

PMID- 21864211
TI  - Exploring the effects of ownership and choice on self-memory biases.
AB  - Objects encoded in the context of temporary ownership by self enjoy a memorial
      advantage over objects owned by other people. This memory effect has been linked
      to self-referential encoding processes. The current inquiry explored the extent
      to which the effects of ownership are influenced by the degree of personal choice
      involved in assigning ownership. In three experiments pairs of participants chose
      objects to keep for ownership by self, and rejected objects that were given to
      the other participant to own. Recognition memory for the objects was then
      assessed. Experiment 1 showed that participants recognised more items encoded as
      "self-owned" than "other-owned", but only when they had been chosen by self.
      Experiment 2 replicated this pattern when participants' sense of choice was
      illusory. A source memory test in Experiment 3 showed that self-chosen items were
      most likely to be correctly attributed to ownership by self. These findings are
      discussed with reference to the link between owned objects and the self, and the
      routes through which self-referential operations can impact on cognition.

PMID- 21864212
TI  - Crafting the TALE: construction of a measure to assess the functions of
      autobiographical remembering.
AB  - Theory suggests that autobiographical remembering serves several functions. This
      research builds on previous empirical efforts (Bluck, Alea, Habermas, & Rubin,
      2005) with the aim of constructing a brief, valid measure of three functions of
      autobiographical memory. Participants (N=306) completed 28 theoretically derived
      items concerning the frequency with which they use autobiographical memory to
      serve a variety of functions. To examine convergent and discriminant validity,
      participants rated their tendency to think about and talk about the past, and
      measures of future time orientation, self-concept clarity, and trait personality.
      Confirmatory factor analysis of the function items resulted in a respecified
      model with 15 items in three factors. The newly developed Thinking about Life
      Experiences scale (TALE) shows good internal consistency as well as convergent
      validity for three subscales: Self-Continuity, Social-Bonding, and Directing
      Behaviour. Analyses demonstrate factorial equivalence across age and gender
      groups. Potential use and limitations of the TALE are discussed.

PMID- 21864213
TI  - SKOOL versus ZOOL: effects of orthographic and phonological long-term memory on
      nonword immediate serial recall.
AB  - In a now-classic study Besner and Davelaar (1982) reported an advantage of
      pseudohomophone (PSH) over nonword recall in a visual immediate serial recall
      (ISR) task, which remained under articulatory suppression (AS), and interpreted
      the findings as indicating PSH items obtain support from stored phonological long
      term memory (LTM) representations even when phonological rehearsal is disrupted.
      However, one key question relating to this PSH effect remains: could the results
      have been contaminated by a potential confound of orthographic familiarity (i.e.,
      PSH items often look like the word they sound like)? As a result, the present
      study examined the impact of orthography on PSH ISR. Our findings indicate that
      PSH accuracy was consistently higher for items that had an orthographic
      similarity to the parent word, and this effect did not interact with concurrent
      task. We therefore argue that PSH items in ISR obtain independent support from
      both orthographic and phonological LTM representations. The present study
      demonstrates the critical impact of orthographic LTM representations on visual
      nonword ISR, and we suggest that this may be a fruitful avenue for further
      research.

PMID- 21864214
TI  - The self in autobiographical memory: effects of self-salience on narrative
      content and structure.
AB  - Contemporary models of autobiographical memory attribute a prominent role to the
      conceptualisation of the self. In an attempt to better understand the impact of
      the self as an organising feature of autobiographical memory, narratives of
      personal episodes were elicited, either after a questionnaire about the self
      (self-prime condition) or after a distractor task (control condition).
      Participants also wrote a narrative of a turning-point memory, which is by
      definition a self-focused narrative. Narratives were divided into propositions
      and analysed for the types of statements used. As predicted, when writing self
      focused turning-point narratives participants included more statements relating
      to the meaning of an event and connecting it to the self, and fewer statements
      focusing on the who, what, where, and when of the narrative. Narratives written
      after the self-prime also demonstrated characteristics that were similar to
      turning-point narratives, although not on all measures. This shift in narrative
      focus in turning-point and self-primed memory narratives indicates an increased
      attempt to fulfil goals of coherence rather than correspondence (Conway, 2005).
      These findings lend insight into the nature of the relationship between the
      semantic conceptualisation of the self, and the process of retrieving event
      specific knowledge in episodic memory.

PMID- 21864215
TI  - No evidence of age-related increases in unconscious plagiarism during free
      recall.
AB  - In three experiments younger and older participants took part in a group
      generation task prior to a delayed recall task. In each, participants were
      required to recall the items that they had generated, avoiding plagiarism errors.
      All studies showed the same pattern: older adults did not plagiarise their
      partners any more than younger adults did. However, older adults were more likely
      than younger adults to intrude with entirely novel items not previously generated
      by anyone. These findings stand in opposition to the single previous
      demonstration of age-related increases in plagiarism during recall.

PMID- 21864216
TI  - Working memory in multilingual children: is there a bilingual effect?
AB  - This research investigates whether early childhood bilingualism affects working
      memory performance in 6- to 8-year-olds, followed over a longitudinal period of 3
      years. The study tests the hypothesis that bilinguals might exhibit more
      efficient working memory abilities than monolinguals, potentially via the
      opportunity a bilingual environment provides to train cognitive control by
      combating interference and intrusions from the non-target language. A total of 44
      bilingual and monolingual children, matched on age, sex, and socioeconomic
      status, completed assessments of working memory (simple span and complex span
      tasks), fluid intelligence, and language (vocabulary and syntax). The data showed
      that the monolinguals performed significantly better on the language measures
      across the years, whereas no language group effect emerged on the working memory
      and fluid intelligence tasks after verbal abilities were considered. The study
      suggests that the need to manage several language systems in the bilingual mind
      has an impact on children's language skills while having little effects on the
      development of working memory.

PMID- 21864217
TI  - Do intrusive memory characteristics predict depression at 6 months?
AB  - Two prospective studies have investigated whether the presence, intrusion, and
      avoidance of negative intrusive memories predict depression, and have reported
      conflicting findings. We aimed to replicate and extend these investigations by
      exploring the role of intrusion and avoidance of intrusive memories, as well as
      memory characteristics, in the prediction of depression prospectively. At Time 1
      a mixed sample of community participants (N=85) were interviewed and completed
      self-report measures of depression, anxiety, and intrusive memory features. At
      Time 2 (6 months later, N=64) depression and anxiety symptoms were reassessed.
      Results were partly consistent with hypotheses for the sub-sample of participants
      who did not receive treatment between the baseline and follow-up assessments.
      Baseline levels of intrusion and some memory features (uncontrollability,
      distress, interference, numbness, detachment) predicted follow-up depression,
      controlling for baseline depression symptoms. Unexpectedly, avoidance of
      intrusive memories and other features (e.g., here and now quality) did not
      predict depression. Levels of intrusion and avoidance did not predict anxiety at
      follow-up. These results provide further evidence that intrusive memories are not
      simply an epiphenomenon of depression, but predict depression prospectively. Our
      results suggest that novel, depression-specific theories that emphasise the role
      of memory disturbances in the maintenance of depression are needed.

PMID- 21864218
TI  - Computational modeling of P450s for toxicity prediction.
AB  - INTRODUCTION: Drug development is a time-consuming and cost-intensive process. On
      average, it takes around 12 - 15 years and approximately ?800 billion to bring a
      new drug to the market. Despite introduction of combinatorial chemistry and
      establishment of high-throughput screening (HTS), the number of new drug entities
      is limited. In fact, a number of established drug entities have been withdrawn
      from the market because of drug-drug interactions (DDIs) and adverse drug
      reactions (ADRs). AREAS COVERED: This review covers the advancements in
      cytochrome P450 (CYP450) modeling using different computational/machine learning
      (ML) tools over the past decade. A computational model for identifying non-toxic
      drug molecule from the pool of small chemical molecules is always welcome in the
      drug industry. Any computational tool that identifies the toxic molecule at early
      stage reduces the economic burden by slashing the number of molecules to be
      screened. This review covers all issues related to CYP-mediated toxicity such as
      specificity, inhibition, induction and regioselectivity. EXPERT OPINION: Several
      computational methods for CYP-mediated toxicity are available, which are popular
      in computer-aided drug designing (CADD). These models may become helpful in
      toxicity prediction during early stages and can reduce high failure rates in
      preclinical and clinical trials. There is an urgent need to improve the accuracy,
      interpretability and confidence of the computation models used in drug discovery
      pathways.

PMID- 21864219
TI  - Health effects of particulate air pollution: A review of epidemiological
      evidence.

PMID- 21864220
TI  - Comparison of mouse strains and exposure conditions in acute cigarette smoke
      inhalation studies.
AB  - Cigarette smoke exposures in mice have been conducted under various exposure
      conditions using different strains as animal models of smoke-related diseases. We
      exposed cigarette smoke to two strains of mice [C57BL/6J (C57) and AKR/J (AKR)]
      under two different exposure regimens (1 h or 4 h/day) at equivalent daily
      exposure amount (concentration * time). After 2 weeks exposure, mice were
      evaluated using exposure markers and biological responses. Smoke exposure
      suppressed respiratory parameters dependent on exposure concentration. The 1-h
      regimen groups generally showed a greater degree of respiratory suppression and
      relatively lower exposure markers of urinary nicotine metabolites than the
      corresponding 4-h regimen groups. Tidal volume was more suppressed in AKR
      compared to C57, while respiratory rate was more suppressed in C57. Plasma
      exposure markers and respiratory parameters suggested that C57 inhaled more
      volume of smoke than AKR. Changes in bronchoalveolar lavage fluid (BALF) cytology
      and enzyme parameters were most noticeable in the 1 h AKR groups. In BALF
      cytokine concentration, TARC concentration in C57 was higher than AKR, while KC
      and MCP-1 in AKR were higher than C57. Relative lung/body weight ratio in smoke
      exposed C57 was generally higher, as well as the incidence and severity of
      lesions in respiratory organs compared to AKR. In summary, C57 appeared to inhale
      relatively more smoke and displayed greater inflammatory changes in respiratory
      tract than AKR. Comparison of exposure regimens suggests that a longer exposure
      duration at lower WTPM concentration might deliver a larger dose of smoke than a
      shorter exposure duration at higher WTPM concentration.

PMID- 21864221
TI  - Elastases from inflammatory and dendritic cells mediate ultrafine carbon black
      induced acute lung destruction in mice.
AB  - CONTEXT: Exposure to ultrafine particles (<100 nm in diameter) is postulated to
      cause chronic obstructive pulmonary disease (COPD). However, the mechanism
      remains to be elucidated. OBJECTIVE: We aimed to evaluate whether ultrafine
      particle exposure causes the infiltration of inflammatory and dendritic cells
      (DCs) with increased elastase activity, contributing to lung parenchymal
      destruction. MATERIALS AND METHODS: C57BL/6 male mice were intratracheally
      instilled with 300 ug ultrafine carbon black (ufCB; 14 nm in diameter), and
      sacrificed at 1, 3, 7 and 14 d post-exposure. Differential cell counts, elastase
      activities, and desmosine and hydroxyproline in bronchoalveolar (BAL) fluid were
      determined. Immunofluorescent staining and flow cytometry analysis determined the
      cell origin of macrophage metalloelastase (MMP-12). Anti-neutrophil antibody was
      applied to assess the contribution of elastase in ufCB induced lung destruction.
      RESULTS: ufCB exposure led to significant increases in neutrophils, mononuclear
      cells and total proteins in BAL fluid. Desmosine and hydroxyproline were
      significantly increased in the ufCB group. Elastase activities were found to be
      significantly elevated, with both neutrophil elastase and MMP-12 peaking at 3 d
      post-exposure. Flow cytometry analysis demonstrated that pulmonary infiltrations
      of MMP-12 positive DCs, including Langerhans cells-derived DCs, occurred at 3 d
      and 7 d, while macrophage infiltration was obvious starting at 1 d. Anti
      neutrophil antibody significantly reduced neutrophil elastase activity and
      prevented the increases in BAL desmosine and hydroxyproline following ufCB
      exposure. CONCLUSION: For the first time we demonstrate the infiltration of
      Langerhans and myeloid dendritic cells, and show that elastase production
      contributes to pulmonary destruction following exposure to ultrafine particles.

PMID- 21864222
TI  - Insulin administration: selecting the appropriate needle and individualizing the
      injection technique.
AB  - INTRODUCTION: Patients with diabetes who receive insulin therapy often fail to
      meet their targets for metabolic control with insulin injections. Their
      inadequate glycemic control may be related to incorrect injection procedure.
      AREAS COVERED: This review examines the latest data related to insulin injection
      and needle characteristics, which play an integral role in patient satisfaction.
      Searches of Medline and Cumulative Index to Nursing and Allied Health Literature
      databases were conducted. Results show that optimal insulin injection can
      facilitate glycemic control in pediatric and adult patients. In general, needles
      shorter than 8 mm are appropriate for normal weight, obese pediatric and adult
      patients. However, body mass index, gender, race, age and injection site can
      influence the depth of subcutaneous tissue and thus, the desired needle size and
      injection technique. Although the abdomen, thighs and buttocks are all
      recommended injection sites, abdominal injections disperse insulin slightly more
      rapidly than thigh injections. EXPERT OPINION: Wider acceptance of needles
      shorter than 6 mm will occur with more evidence of their safety and efficacy,
      particularly in children. Development of shorter and thinner needles to make
      injections even easier and less burdensome may be expected in the future.

PMID- 21864223
TI  - Are there health effects of harassment in the workplace? A gender-sensitive study
      of the relationships between work and neck pain.
AB  - The aim of this study was to identify workplace physical and psychosocial risk
      factors for neck pain among male and female workers and, in particular, to study
      the relationship between neck pain and intimidation and sexual harassment in the
      workplace in a representative sample of the Quebec working population. The study
      sample included 5405 men and 3987 women. In multiple logistic regression
      analyses, when taking into account individual and other workplace factors, neck
      pain was significantly associated with intimidation at work among both male (odds
      ratio (OR) 1.4 (1.01-1.8)) and female workers (OR 1.3 (1.01-1.8)). Among female
      workers, neck pain was alsosignificantly associated with unwanted sexual
      attention (OR 1.6 (1.1-2.4)). If confirmed in prospective studies, these results
      suggest that interventions to prevent harassment in the workplace may help reduce
      musculoskeletal disorders in the workplace and that workplace programmes to
      reduce harassment in the workplace should include prevention of sexual
      harassment. PRACTITIONER SUMMARY: While taking into account relevant personal
      factors and previously identified workplace physical and psychosocial risk
      factors, this gender-based study identifies new work exposures associated with
      neck pain that have not previously been studied, including unwanted sexual
      attention, intimidation and difficult or tense situations with the public.

PMID- 21864224
TI  - Blocking the interaction of vascular endothelial growth factor receptors with
      their ligands and their effector signaling as a novel therapeutic target for
      cancer: time for a new look?
AB  - INTRODUCTION: The interaction between the VEGFRs and their ligands plays an
      important role in tumor angiogenesis. Despite a series of problems encountered
      during early work on blocking growth factors, current evidence injects further
      vigor into researching the modulation of VEGFR activity. Emerging preclinical and
      clinical studies suggest that attenuating receptor activity can synergistically
      promote antitumor action if utilized concurrently with conventional therapies.
      AREAS COVERED: This review presents an up-to-date assessment of the potential
      role of modulating receptor activities in various cancers. The sentinel work on
      the proof of principles in various animal models, and the current translational
      research on these small molecule inhibitors and receptor blocking antibodies,
      from Phase I to Phase III trials, has been systematically examined with an
      emphasis on agents in earlier stages of development. EXPERT OPINION: Many
      clinical trials are ongoing, but early phase trials show promising results.
      Recently, there has been a huge explosion of research activity either in the
      development of new drugs or in the understanding its biology. Many current trials
      lend support to the rationale behind these therapies, which can function as
      adjuvants to conventional treatments. It has been argued that normalization of
      tumor-induced vasculature can promote better drug delivery and prevent resistance
      to radiotherapy. However, strategies involving the inhibition of the interaction
      of VEGFRs with ligands and their downstream pathways are not, in general, at a
      stage where it will be directly useful in clinical cancer treatment. A deeper
      understanding of these biologic therapies will help to improve the efficacy of
      conventional treatments and furthermore reduce dose-dependent cytotoxic activity.

PMID- 21864226
TI  - ?

PMID- 21864225
TI  - The compartmentalization and translocation of the sphingosine kinases: mechanisms
      and functions in cell signaling and sphingolipid metabolism.
AB  - Members of the sphingosine kinase (SK) family of lipid signaling enzymes,
      comprising SK1 and SK2 in humans, are receiving considerable attention for their
      roles in a number of physiological and pathophysiological processes. The SKs are
      considered signaling enzymes based on their production of the potent lipid second
      messenger sphingosine-1-phosphate, which is the ligand for a family of five G
      protein-linked receptors. Both SK1 and SK2 are intracellular enzymes and do not
      possess obvious membrane anchor domains within their primary sequences. The
      native substrates (sphingosine and dihydrosphingosine) are lipids, as are the
      corresponding products, and therefore would have a propensity to be membrane
      associated, suggesting that specific membrane localization of the SKs could
      affect both access to substrate and localized production of product. Here, we
      consider the emerging picture of the SKs as enzymes localized to specific
      intracellular sites, sometimes by agonist-dependent translocation, the mechanism
      targeting these enzymes to those sites, and the functional consequence of that
      localization. Not only is the signaling output of the SKs affected by subcellular
      localization, but the role of these enzymes as metabolic regulators of
      sphingolipid metabolism may be impacted as well.

PMID- 21864227
TI  - Bisphosphonates and breast cancer prevention.
AB  - Bisphosphonates are commonly used in patients with breast cancer to reduce
      skeletal-related events in metastatic disease and to mitigate bone loss
      associated with cancer therapy in early stage disease. In addition, adjuvant
      breast cancer trials evaluating the oral bisphosphonate clodronate suggested a
      reduction in cancer recurrence, but the findings were mixed, with 2 positive and
      1 negative report. In the Austrian Breast and Colorectal Cancer Study Group
      (ABCSG) 12 study, adding the intravenous bisphosphonate zoledronic acid to
      endocrine therapy in premenopausal breast cancer patients significantly prolonged
      disease-free survival versus endocrine therapy alone (hazard ratio = 0.68; p =
      0.008) at 62 months, and reduced local, regional, and distant recurrences.
      Clinical trial findings from other adjuvant trials (Z-FAST, ZO-FAST), neoadjuvant
      studies, and studies involving disseminated tumor cells (DTCs) are generally
      supportive of the ABCSG-12 conclusion, and recent data from AZURE suggest the
      importance of menopausal status. Preclinical studies provide data on the
      mechanisms of action that could mediate bisphosphonate direct and indirect anti
      cancer effects. Recently, several observational studies (2 cohort studies and 2
      case-control analyses) have associated oral bisphosphonate use with a lower
      breast cancer incidence. Such reports require cautious interpretation because
      confounding by indication is an issue: bisphosphonates are prescribed for women
      with low bone mineral density, and women with low bone density are at decreased
      breast cancer risk.

PMID- 21864228
TI  - Bisphosphonate anticancer activity in multiple myeloma.
AB  - Bisphosphonates inhibit osteoclast-mediated bone resorption and have been used
      extensively to prevent skeletal-related events in patients with bone lesions from
      multiple myeloma (MM). In addition, in vitro and in vivo preclinical data suggest
      that bisphosphonates also have antimyeloma properties that may induce myeloma
      cell apoptosis, activate an anticancer immune response, inhibit angiogenesis, and
      reduce tumor burden, supporting an expanded role for bisphosphonates. Signals for
      improved survival in the clinic first emerged in retrospective analyses of MM
      patient subgroups in larger clinical trials. Recently, improved progression-free
      survival and overall survival with bisphosphonates have been reported in the
      overall populations of large-scale randomized clinical trials. Several ongoing
      clinical trials will help further define the role of bisphosphonates during
      antimyeloma therapy. Overall, bisphosphonates appear to be well tolerated in
      patients with MM; the most common adverse events are mild and can be easily
      managed. However, emphasis on renal monitoring and preventive dentistry are
      necessary to reduce the risk of potential adverse events, and have become the
      standard of care for patients with MM.

PMID- 21864229
TI  - Bisphosphonate anticancer activity in prostate cancer and other genitourinary
      cancers.
AB  - Anticancer therapies have traditionally been targeted directly against cancer
      cell growth. However, newer treatment strategies also target the microenvironment
      that supports metastatic cancer cell growth. Bisphosphonates are the standard of
      care for maintaining bone health in patients with bone metastases from solid
      tumors and bone lesions from multiple myeloma, and emerging evidence supports
      potential anticancer activity of bisphosphonates. Zoledronic acid (ZOL), a third
      generation nitrogen-containing bisphosphonate, is currently advised for reducing
      the risk of skeletal morbidity in patients with bone metastases from prostate
      cancer and other genitourinary cancers, such as renal cell carcinoma and bladder
      cancer. Clinical studies indicate that ZOL can normalize bone marker levels (a
      potential measure of skeletal disease burden), which may improve survival in
      patients with aggressive bone disease from prostate and other genitourinary
      cancers, supporting a broader therapeutic role for ZOL in genitourinary
      malignancies. This review examines the rationale and emerging evidence supporting
      the anticancer activity of bisphosphonates, especially ZOL, against prostate and
      other genitourinary cancers.

PMID- 21864230
TI  - The chemistry of bisphosphonates: from antiscaling agents to clinical
      therapeutics.
AB  - In the early 1960s, inorganic pyrophosphate (PPi) was found to be present in body
      fluids and to act as a natural inhibitor of calcification by its interaction with
      hydroxyapatite. In addition to inhibiting the formation of calcium phosphate, PPi
      also inhibited dissolution of hydroxyapatite crystals, which made it interesting
      for pharmacologic applications in the treatment of diseases associated with
      excessive bone resorption. However, PPi is metabolically unstable because of
      rapid hydrolysis of the P-O-P backbone by hydrolytic enzymes in the
      gastrointestinal tract. In the search for more stable analogues of PPi, attention
      turned to the chemical class of bisphosphonates (BPs). The first BPs were
      synthesized in the 19th century and widely used for industrial applications.
      Bisphosphonates are formally derived from PPi by replacement of the bridging
      oxygen atom by a carbon atom, resulting in a P-C-P moiety that is resistant to
      hydrolysis. In addition to its decisive role in stability, the central carbon
      atom also provides an attachment point for 2 additional substituents (R1 and R2).
      While R1 is preferentially a hydroxy group, allowing such derivatives to act as
      powerful tridentate ligands for calcium (bone hook), R2 is mainly responsible for
      antiresorptive potency. The clinically available BPs can be divided into 2
      subclasses based on their structure and molecular mechanism of action. The
      simple, non-nitrogen-containing derivatives can be incorporated into non
      hydrolyzable cytotoxic ATP analogues. The more potent nitrogen-containing BPs
      inhibit FPPS, a key enzyme in the mevalonate pathway. Details of this crucial
      molecular interaction have recently been elucidated. Members of this class have a
      wide therapeutic window between therapeutic inhibition of bone resorption and
      undesired inhibition of bone formation, and several have found widespread use for
      the treatment of benign and malignant bone disease.

PMID- 21864231
TI  - Anticancer activity of bisphosphonates in breast cancer.
AB  - Despite progress in surgical and adjuvant therapy, a subset of patients with
      early stage breast cancer experience disease recurrence and/or distant
      metastases. Disseminated tumor cells (DTCs) in the bone marrow are believed to be
      the source of late relapses in bone and other tissues. Bone is the most common
      site of breast cancer metastasis, and agents that modify the bone
      microenvironment could therefore affect the disease course. Bisphosphonates are
      an effective bone-targeted therapeutic option for preventing cancer treatment-
      induced bone loss (CTIBL) in pre- and postmenopausal women with breast cancer.
      Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting
      the release of growth factors necessary to promote cancer cell growth,
      differentiation, and tumor formation in bone. Preclinical and clinical data also
      suggest anticancer synergy between cytotoxic chemotherapy agents and
      bisphosphonates. Recent trials of zoledronic acid in the adjuvant setting in
      breast cancer have demonstrated reduced disease recurrence in bone and other
      sites. Currently, several ongoing clinical trials are evaluating whether
      antiresorptives can inhibit disease recurrence and the development of bone
      metastases from breast cancer. Based on recent data, the role of bisphosphonates
      in the breast cancer setting is expected to expand in the future. With recent
      changes to treatment guidelines, routine use of bisphosphonates to prevent bone
      loss during adjuvant therapy is likely to become standard practice, especially
      for patients receiving endocrine therapy. Furthermore, the use of zoledronic acid
      to reduce the risk of recurrence is emerging based on ongoing clinical research.

PMID- 21864232
TI  - Potential anticancer properties of bisphosphonates: insights from preclinical
      studies.
AB  - Bone is a common site of metastasis from advanced cancers, and metastasis to bone
      accounts for the majority of distant recurrences from breast and prostate
      cancers. Bone metastases are characterized by increased rates of bone turnover.
      Bisphosphonates are extensively used in the treatment of metastatic bone disease
      to reduce the rates of osteolysis and the risk of skeletal-related events. In
      addition, bisphosphonates have demonstrated direct and indirect anticancer
      potential in preclinical studies. These activities include induction of
      apoptosis, inhibition of invasion, synergistic cytotoxicity with chemotherapy
      agents, antiangiogenic properties, and modulation of immunologic activity against
      transformed cells. Notably, these activities of bisphosphonates are not limited
      to the bone microenvironment; indeed some effects are mediated on the cancer
      cells themselves. These preclinical data provide the rationale for the underlying
      potential clinical benefits from bisphosphonates (e.g., prevention of metastasis
      to bone and other sites in the early breast cancer setting and delayed disease
      progression in malignancies involving colonization of bone [e.g., multiple
      myeloma]). This review article summarizes the preclinical anticancer activities
      of bisphosphonates in various cancer types and evaluates their potential
      contributions to the recently demonstrated clinical effects.

PMID- 21864233
TI  - Bisphosphonates in lung cancer: can they provide benefits beyond prevention of
      skeletal morbidity?
AB  - Bisphosphonates are the current standard of care for patients with bone
      metastases from advanced solid tumors. Zoledronic acid has demonstrated the
      broadest activity in this setting, and is approved for the prevention of skeletal
      related events from bone metastases from a variety of solid tumors in addition to
      breast cancer and multiple myeloma. Ongoing studies are evaluating the
      antiresorptive potentials of investigational agents in these settings. A large
      body of preclinical evidence and recent clinical developments support the
      hypothesis that zoledronic acid can exert clinically meaningful anticancer
      activities in some settings, thereby improving disease outcomes and survival.
      These data are especially strong in breast cancer and multiple myeloma, and are
      emerging in other cancer settings. This review article will discuss the emerging
      data suggesting an anticancer role for bisphosphonates in the context of lung
      cancer and solid tumors other than breast and genitourinary malignancies.

PMID- 21864235
TI  - Gold nanostructures as photothermal therapy agent for cancer.
AB  - Well-designed photothermal nanostructures have attracted many scientists pursuing
      a better means to accurately diagnose cancer and assess the efficacy of
      treatment. Recently, gold-based nanostructures (nanoshells, nanorods and
      nanocages) have enabled photothermal ablation of cancer cells with near-infrared
      (NIR) light without damaging normal human tissues and in particular, animal
      studies and early clinical testing showed the great promise for these materials.
      In this review article, we first discuss the mechanism of the cellular death
      signaling by thermal stress and introduce the intrinsic properties of gold
      nanostructures as photothermal agent for cancer treatment. Then the overview
      follows for evolving researches for the synthesis of various types of gold
      nanostructures and for their biomedical applications. Finally we introduce the
      optimized therapeutic strategies involving nanoparticle surface modification and
      laser operation method for an enhanced accumulation of gold nanostructures to the
      target cancer as well as for an effective cancer cell ablation.

PMID- 21864234
TI  - Cancer nanotechnology: emerging role of gold nanoconjugates.
AB  - Over the last few decades, the study of nanotechnology has grown exponentially.
      Nanotechnology bridges science, engineering and technology; it continues to
      expand in definition as well as practice. One sub-set of nanotechnology is
      bionanotechnology, this will be the focus of this review. Currently,
      bionanotechnology is being studied and exploited for utility within medicinal
      imaging, diagnosis and therapy in regard to cancer. Cancer is a world-wide health
      problem and the implication rate as well as the death rate increase year to year.
      However promising work is being done with gold nanoparticles for detection,
      diagnosis and targeted drug delivery therapy. Gold nanoparticles can be
      synthesized in various shapes and sizes, which directly correlates to the color;
      they can also be manipulated to carry various antibody, protein, plasmid, DNA or
      small molecule drug. Herein we summarize some of the very influential research
      being done in the field of Cancer Nanotechnology with an emphasis on gold
      nanoparticles.

PMID- 21864236
TI  - Strategies for the biological evaluation of gold anticancer agents.
AB  - Since the introduction of the monomeric orally bioavailable anti-arthritic gold
      compound auranofin in 1985, and the success of the platinum-based anti-cancer
      drugs, there has been a great deal of interest in the use of gold compounds for
      cancer therapy. However this early promise has not materialized into an approved
      drug in spite of extensive and innovative efforts in gold chemistry. Therefore,
      in the light of this lack of success, the strategies for the biological
      evaluation of potential gold-based anti-cancer drugs are discussed. It is
      proposed that the biological testing strategy should be multi-faceted
      incorporating an understanding of the molecular properties of the compounds under
      investigation related to their behaviour in a biological environment, an
      evaluation of their comparative in vitro potency against tumor cells,
      ascertaining the biochemical mechanism of action and target identification to aid
      in medicinal chemistry design, evaluation of in vivo activity in relevant tumor
      models, and an understanding of their toxicological and pharmacokinetic
      properties. This strategy will be exemplified with work on Au(III)
      cyclometallated complexes in which an integrated approach to the search for new
      metal-based anticancer drugs was adopted, incorporating in vitro screening, in
      vivo human tumor xenograft models, and mechanistic studies. The importance of
      mechanistic studies which have led to the identification of new molecular targets
      for gold drugs, and in vivo evaluation are emphasized.

PMID- 21864237
TI  - Protein targets for anticancer gold compounds: mechanistic inferences.
AB  - Gold compounds form an interesting class of antiproliferative agents of potential
      pharmacological use in cancer treatment. Indeed, a number of gold compounds,
      either gold(III) or gold(I), were recently described and characterised that
      manifested remarkable cytotoxic properties in vitro against cultured cancer
      cells; for some of them encouraging in vivo results were also reported toward a
      few relevant animal models of cancer. The molecular mechanisms through which gold
      compounds exert their biological effects are still largely unknown and the
      subject of intense investigations. Recent studies point out that the modes of
      action of cytotoxic gold compounds are essentially DNA-independent and cisplatin
      unrelated, relying -most likely- on gold interactions with a variety of protein
      targets. Notably, a few cellular proteins playing relevant functional roles were
      proposed to represent effective targets for cytotoxic gold compounds but these
      hypotheses need adequate validation. The state of the art of this research area
      and the perspectives for future studies are herein critically analysed and
      discussed.

PMID- 21864238
TI  - Phosphine-gold(I) compounds as anticancer agents: general description and
      mechanisms of action.
AB  - Gold complexes have been explored as metallodrugs with great potential
      applications as antitumoral agents. In particular, gold-phosphine derivatives
      seemed quite promising since the use of the antiarthritic auranofin drug
      (thiolate-Au-PEt3 complex) presented also biological activity against different
      cancer cells. So, different auranofin analogues have been explored within this
      context and for this reason, the main number of phosphine-gold complexes
      developed with this goal contain thiolate ligands. Other complexes have been also
      studied such as tetrahedral bis(phosphine)gold(I) and phosphine-gold-halides.
      Very recently, phosphine-gold-alkynyl complexes have also shown very interesting
      biological activities although few reports are published related to them. Their
      mechanism of action seems to be clearly different that the used by platinum drugs
      (DNA intercalating processes) and recent studies point to be related to the
      inhibition of Trx reductase. Cellular uptake and biodistribution studies are well
      reported in the original works but the use of luminescence techniques is
      relatively less explored. For this, the use of these techniques is also
      specifically reported in this review.

PMID- 21864239
TI  - Editorial: targeted therapy for glioblastoma multiforme.

PMID- 21864240
TI  - Sphingolipid modulation: a strategy for cancer therapy.
AB  - Sphingolipids are membrane lipids that play important roles in the regulation of
      cell functions and homeostasis. Alterations in their metabolism have been
      associated with several pathologies. For this reason, therapeutic strategies
      based on the design of small molecules to restore sphingolipid levels to their
      physiological condition have rapidly emerged. In addition, some of these new
      chemical entities, even if they fail to succeed along the pipeline, can become
      valuable pharmacological tools for the study of sphingolipid function.
      Implications of altered sphingolipid metabolism in cancer progression have
      allowed the identification of new targets for the development of potential
      anticancer agents. Based on these premises, this review is focused on the most
      recent achievements in the field, with special attention to the development of
      small molecules, mainly enzyme inhibitors, able to disrupt some of the key
      sphingolipid metabolic pathways implicated in cancer progression. On the other
      hand, metabolic dysregulation can also be modulated by the use of sphingolipid
      analogs, which can alter the sphingolipid balance driving cells to death or
      survival and thus becoming useful candidates for subsequent drug development.

PMID- 21864241
TI  - Biochemistry and biology of 2'-Fluoro-2'-deoxythymidine (FT), a putative highly
      selective substrate for thymidine kinase type 2 (TK2).
AB  - 2'-Deoxy-2'-fluorothymidine (FT) is a bioisostere of both thymidine (TdR), in
      which F replaces H at C-2' in the ribosyl configuration, and methyluridine, in
      which F replaces OH at C-2' in the ribosyl configuration. Fluorine is
      bioisosteric with H with respect to atomic radius and is bioisosteric with OH
      with respect to polarity and H-bonding as an H acceptor. The consequences of this
      C-2' F for H substitution on cytotoxicity, nucleoside transporter affinity,
      phosphorylation by thymidine kinases (TK1, TK2), cell uptake and biodistribution
      of FT in a murine tumor model are now reported. FT toxicity against a bank of
      murine and human cells was seen only at very high (~1 mM) concentrations,
      although the cellular uptake of [3H]FT in these cells was comparable to that of
      [3H]TdR over a 24 h period. Human equilibrative nucleoside transporters (hENT1,
      hENT2) displayed weaker affinity for FT than for TdR, but the concentrative
      transporters (hCNT1, hCNT2, hCNT3) had much higher affinities for FT. FT was
      phosphorylated by both mitochondrial thymidine kinase (TK2) (58 % of TdR) and
      cytosolic thymidine kinase (TK1) (39 % of TdR). Preliminary in vivo imaging with
      [18F]FT in mice bearing implanted KBALB and contralateral KBALB-STK tumors showed
      highly selective uptake, with a tumor:blood ratio of 33 in a small herpes simplex
      type 1 (HSV-1 TK) expressing tumor. In conclusion, [18F]FT appears to be a strong
      candidate for PET imaging of viral TK transgene imaging, based on its TK1:TK2
      phosphorylation differential, its selective uptake by an HSV-TK expressing murine
      tumor model, its interaction with nucleoside transporters and its low toxicity.

PMID- 21864242
TI  - Synthesis and preliminary evaluation of n.c.a. iodoquine: a novel radiotracer
      with high uptake in cells with high ALDH1 expression.
AB  - PURPOSE: Chloroquine has demonstrated high affinity for aldehyde dehydrogenase
      1A1 (ALDH1), an enzyme expressed in the highly tumorigenic CD133+ brain tumor
      initiating subpopulation. The purpose of this study is to report the novel
      synthesis of a chloroquine analogue, n.c.a. iodoquine, and the in vitro and in
      vivo uptake in cells with high ALDH1 content. METHODS AND MATERIALS: Iodoquine
      was synthesized in novel no-carrier-added forms (n.c.a.) for both 125I and 123I.
      I25I IQ and 18F FDG cell uptake assays were performed in the L1210 and L1210cpa
      (cyclophosphamide resistant), A549, and MG456 glioblastoma cell lines. Uptake was
      expressed as a percent of the administered activity. 125I IQ biodistribution
      studies assessed organ uptake at 1, 4, and 24 hours after IV administration (n=
      15 total; 5 mice/timepoint). Radiation dosimetry estimates were calculated using
      standard OLINDA/EXM software. In vivo imaging of 123I IQ uptake in MG456
      glioblastoma mouse model (n=10) was performed with small animal high resolution
      micro-SPECT. Autoradiography and histology co-localized radiotracer and tumor
      biodistribution. Uptake in MG456 glioblastoma tumors was quantified with gamma
      counting. RESULTS: L1210 cpa (high ALDH1) showed significantly higher 125I IQ
      uptake compared to the parental L1210 (low ALDH1) for all time points through 4
      hours (20.7% +/- 1.4% versus 11.0% +/- 0.5%; 21.3% +/- 0.9% versus 11.0% +/-
      0.4%; 20.6% +/- 0.7% versus 9.4% +/- 0.3%; and 15.7% +/- 0.7% versus 7.5% + 0.4%
      at 30 minutes, and 1, 2 and 4 hours, respectively; p < 0.001 for all time
      points). In the CD133+ fraction of MG456 glioblastoma cell line, IQ uptake was
      significantly higher compared to FDG at all time points through 4 hours (81.5% +/
      0.9% versus 1.3% +/- 0.1%; 88.8% +/- 0.4% versus 1.3% +/- 0.1%; 87.8% +/- 2.1%
      versus 1.7% +/- 0.2%; and 87.0% +/- 2.4% versus 1.8% +/- 0.1 at 30 minutes, and
      1, 2 and 4 hours, respectively; p > 0.001 for all time points). The A549 lung
      cancer cell line also showed high IQ uptake through 4 hours. IQ normal
      biodistribution studies showed rapid renal excretion and very low normal
      background brain activity after IV administration. In vivo micro-SPECT images
      showed mild uptake in larger MG456 glioblastomas (n=6) as verified with
      autoradiography and histology. Gamma well counter uptake in large tumors was 2.3%
      +/- 0.48% ID/g (n=5). CONCLUSION: Iodoquine localizes to cells with high ALDH1
      content. Cell assays show high 125I IQ uptake in the MG456 cell line, and in vivo
      micro-SPECT imaging showed mild 123I IQ uptake in MG456 glioblastomas. Further
      studies are necessary to investigate 131I IQ as a potential therapeutic agent
      targeting the highly tumorigenic CD133+ brain tumor stem cell subpopulation.

PMID- 21864243
TI  - RNA synthesis in the pancreatic acinar cells of aging mice as revealed by
      electron microscopic radioautography.
AB  - For the purpose of studying the aging changes of macromolecular synthesis in the
      pancreatic acinar cells of experimental animals, we studied 10 groups of aging
      mice during development and aging from fetal day 19 to postnatal month 24. They
      were injected with 3H-uridine, a precursor for RNA synthesis, sacrificed and the
      pancreatic tissues were taken out, fixed and processed for light and electron
      microscopic radioautography. On many radioautograms the localization of silver
      grains demonstrating RNA synthesis in pancreatic acinar cells in respective aging
      groups were analyzed qualitatively. The number of mitochondria per cell, the
      number of labeled mitochondria with silver grains and the number of silver grains
      in each cell in respective aging groups were analyzed quantitatively in relation
      to the aging of animals. The results revealed that the RNA synthetic activity as
      expressed by the incorporations of RNA precursor, i.e., the number of silver
      grains in cell nuclei, cell organelles, changed due to the aging of animals. The
      number of mitochondria, the number of labeled mitochondria and the mitochondrial
      labeling index labeled with silver grains were counted in each pancreatic acinar
      cell. It was demonstrated that the number of mitochondria, the number of labeled
      mitochondria and the labeling indices showing RNA synthesis at various ages
      increased from embryonic day 19 to postnatal newborn day 1, 3, 9, 14, adult month
      1, 2 and 6, reaching the maxima, then decreased to senile stage at postnatal year
      1 to 2, indicating the aging changes. Based upon our findings, available
      literature on macromolecular synthesis in mitochondria of various cells are
      reviewed.

PMID- 21864245
TI  - Synthesis of [64Cu]Cu-NOTA-Bn-GE11 for PET imaging of EGFR-rich tumors.
AB  - Epidermal growth factor receptors (EGFR) are over-expressed in many different
      types of cancer, thus, are logical targets for both diagnosis and therapy.
      Antibodies and antibody fragments targeting the extracellular EGF receptor and
      small molecules targeting the intracellular tyrosine kinase (TK) part of EGFR
      have been developed as possible diagnostic EGFR imaging agents. Recently, a 12
      amino acid peptide, GE11, was identified using phage display screening to have
      high affinity for EGFR (Kd=22nM). Reported in vitro and in vivo characteristics
      of GE11 suggest that positron-labeled GE11 may be a useful PET imaging agent in
      selecting patients with EGFR-rich tumors who can most benefit from anti- EGFR
      therapy. To enable the exploration of this possibility, positron emitting
      [64Cu]Cu-NOTA-Bn-GE11 was prepared for further evaluation as PET EGFR imaging
      agent.

PMID- 21864246
TI  - Preparation of 99mTc(CO)3-Carboxymethylthioethyl iminodiacetic acid and
      evaluation as a potential renal imaging agent.
AB  - The ligand, carboxymethylthioethyl iminodiacetic acid (CMT-IDA) has a suitable
      array of donor atoms for coordination with [99mTc(CO)3]+ core, wherein the
      resultant complex is expected to possess free carboxylic residues contributing
      towards hydrophilicity of the complex. The aim of the studies was to study the
      renal clearance of 99mTc(CO)3- labeled CMT-IDA and determine the potential of the
      complex towards its use as a renal tubular imaging agent. METHODS: CMT-IDA was
      radiolabeled with the [99mTc(CO)3(H2O)3]+ precursor and was characterized by
      reverse phase HPLC gradient elution system. Stability, hydrophilicity and plasma
      protein binding studies were carried out for the complex. Biodistribution studies
      were carried out in normal male Swiss mice at 10 min.p.i. and 2 h.p.i. The
      clearance was estimated from the activity observed in the urinary bladder by
      tying the urethra prior to injection of the complexes under study. Imaging
      studies were performed with male Swiss mice administered with [99mTc(CO)3(CMT
      IDA)]-2 at 30 min. p.i. and blocking studies were carried out by intraperitoneal
      injection of probenecid 10 min. prior to the injection of the radiotracer.
      RESULTS: [99mTc(CO)3(CMT-IDA)]-2 could be obtained in > 98% radiochemical purity.
      The complex showed renal clearance of 71.0? 5.9% ID at 10 min.p.i. which
      increased to 84.1? 10.6% ID at 2 h.p.i., with no major activity in blood, liver,
      heart, lungs, stomach and spleen. However, the intestinal uptake was high (10.3?
      2.0% ID) at 2 h.p.i. Scintigraphic image of the animal injected with probenecid
      showed an increase in the activity in kidneys indicating excretion of the
      [99mTc(CO)3(CMT-IDA)]-2 complex via tubular pathway. CONCLUSION: The complex,
      [99mTc(CO)3(CMT-IDA)]-2 has shown excellent renal clearance and thereby can be
      explored further for potential use as an agent towards assessing effective renal
      plasma flow.

PMID- 21864247
TI  - Investigation of the dependence of inactivation coefficient on pertinent physical
      quality parameters to low doses ionizing radiation.
AB  - Inactivation constant for V79 cells has been extracted from radiobiology
      experiments that utilize charged particles to irradiate mammal cells in vitro.
      Physical parameters such as effective charge, radiation mean free path and linear
      ionization which characterized protons and heluim-4 particles are determined
      using of standard values. The relationship between inactivation constant alpha
      and physical quality parameters have been determined, in this research, for
      protons and heluim-4 particles. This approach allows getting the characteristic
      biological response of inactivation of V79 cells in terms of each selected
      physical quality parameter. The best regression models are formulated for each
      obtained relationship.

PMID- 21864248
TI  - Prevention and treatment of diabetic retinopathy: evidence from large, randomized
      trials. The emerging role of fenofibrate.
AB  - Diabetic retinopathy (DR) remains a leading cause of preventable vision loss,
      despite advances in diabetes care. The burden of DR is likely to increase as the
      evolving pandemic of type 2 diabetes progresses. Tight control of blood glucose
      levels and blood pressure are essential for preventing or arresting the
      development of diabetic retinopathy, but are often difficult to achieve, and DR
      thus develops in a high proportion of patients. Current treatments for DR such as
      laser photocoagulation, intravitreous injections of corticosteroids or anti
      vascular endothelial growth factor (VEGF) agents are indicated for advanced DR
      and have significant adverse effects. Therefore, new pharmacological treatments
      for the early stages of DR are needed. The Action to Control Cardiovascular Risk
      in Diabetes (ACCORD) trial included a lipid management arm, in which patients
      satisfying additional inclusion criteria for the atherogenic dyslipidemia
      phenotype were randomly assigned to fenofibrate or placebo, each with a statin.
      In the ACCORD-EYE substudy, randomization to fenofibrate was associated with a
      significant reduction in the risk of progression of DR. These data confirm and
      extend the results of the Fenofibrate Intervention and Event Lowering in Diabetes
      (FIELD) study, in which type 2 diabetes patients randomized to fenofibrate
      benefitted from a significantly lower incidence of laser treatment for
      retinopathy, progression of retinopathy or a composite measure of retinopathy
      outcomes. The results of ACCORD-EYE, together with those of FIELD, identify a
      place for fenofibrate for the prevention of retinopathy alongside intensive
      management of traditional risk factors, such as hyperglycemia and high blood
      pressure.

PMID- 21864250
TI  - The potential role of radiation therapy in Bowen's disease: a review of the
      current literature.
AB  - BACKGROUND: Bowen's disease is a form of squamous cell carcinoma in situ that can
      be transformed into invasive squamous cell carcinoma and should be treated
      according to its anatomical position. The aim of this article is to offer an
      overview of treatment options with an emphasis on radiation therapy in the
      treatment of Bowen's disease. METHODS AND MATERIALS: We performed overview of the
      literature based on database searches in PubMed/MEDLINE and we included articles
      till December 2010. Only papers published in English were included. RESULTS:
      There was no standard fractionation regimen: some physicians prescribed high
      doses, such as the ones of invasive skin cancer, whereas others prescribed lower
      doses because of the noninvasive nature of the disease, the sensitive anatomic
      location (e.g., extremity) and the large treatment area. Various studies
      demonstrate high rates of tumor control with minimal morbidity following
      definitive radiation therapy in the treatment of Bowen's Disease. Through a
      multidisciplinary assessment, the treatment of Bowen's disease can be
      individualized to optimize patient care. CONCLUSIONS: Radiation therapy is an
      effective treatment option for Bowen's disease of the skin. Local recurrences
      seem to be equally low in patients treated with high- and low-dose regimens.
      Radiotherapy preserves normal tissues ensuring a superior esthetic and functional
      outcome.

PMID- 21864251
TI  - Esophagitis, treatment-related toxicity in non-small cell lung cancer.
AB  - OBJECTIVES: Radiation esophagitis represents a significant complication
      experienced by non-small cell cancer (NSCLC) patients receiving thoracic
      irradiation. The objective of the current review was to assess the clinical and
      dosimetrical parameters that may predict radiation esophagitis. METHODS: Studies
      were identified by searching PubMed electronic databases. Both prospective and
      retrospective studies were included. Information regarding clinical and
      dosimetrical parameters predicting for radiation-induced esophagitis was
      extracted and analyzed. RESULTS: The esophageal clinical and dosimetric
      parameters that best predict acute esophagitis remain unclear. In many reports,
      Vx (the volume of esophagus receiving x Gy) stands out, with values of x ranging
      from 20-70 Gy. Other studies conclude that the maximal dose received by any point
      of the esophagus is the best predictor of esophagitis. Another metric implicated
      with esophageal toxicity in some reports is the proportion of the esophageal
      circumference or surface area that receives high doses of radiation. CONCLUSIONS:
      Technological advancements in patient immobilization, setup verification, and
      radiotherapy delivery are increasingly being employed to limit the toxicity of
      thoracic irradiation. Future efforts are required to determine how these complex
      techniques should best be implemented to minimize the risks of acute and long
      term esophageal injury.

PMID- 21864253
TI  - Bioavailability enhancement strategies: basics, formulation approaches and
      regulatory considerations.
AB  - Poor solubility remains a major challenge for pharmaceutical industry, which is
      now considered to be an area of prime importance in the field of biomedical
      research. Approximately 40% new molecular entities (NMEs) synthesized in
      pharmaceutical R with advanced combinatorial chemistry and computer aided drug
      designing (CADD) approaches suffer from poor solubility and bioavailability
      related issues. Apart from these presence of intestinal tight junctional
      epithelial cells, transporters and enzymatic barriers further reduces the oral
      absorption of drugs. Implication of the novel lipid based nanocarriers and
      nanomaterials like dendrimers and carbon nanotubes as a delivery system can
      effectively enhance the oral bioavailability of drugs by breaching the barriers,
      and resolve all critics related to solubility and bioavailability. Thus prime
      objectives of this review are to give in-depth knowledge and critical appraisal
      on the barriers for poor oral bioavailability of drugs, along with various novel
      formulation approaches used for bioavailability enhancement such as lipid based
      formulations, nanosizing techniques, complexation with polymers and nanomaterials
      like dendrimers, carbon nanotubes, and penetration enhancers. Also it gives a
      brief account on in vitro, in vivo screening methods used for assessment of oral
      bioavailability, and regulatory considerations for the approval.

PMID- 21864252
TI  - Positron emission tomography for neck evaluation following definitive treatment
      with chemoradiotherapy for locoregionally advanced head and neck squamous cell
      carcinoma.
AB  - OBJECTIVES: The objective of the current review was to assess published data on
      the role of Positron Emission Tomography (PET) for evaluation of nodal residual
      disease after definitive chemoradiotherapy for head and neck squamous cell
      carcinoma (HNSCC). METHODS: Studies were identified by searching PubMed
      electronic databases. Only studies using a post-chemoradiotherapy PET for nodal
      residual disease evaluation were included in the present review. Both prospective
      and retrospective studies were included. Information regarding sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of PET for detecting nodal residual disease after definitive chemoradiotherapy
      for HNSCC was extracted and analyzed. RESULTS: Twenty published studies were
      included in the present review. Existing data suggest that a negative post
      chemoradiotherapy PET scan is associated with a negative predictive value up to
      100%. The sensitivity of PET in detecting nodal residual disease is greater for
      scans performed >= 10 weeks after definitive treatment with chemoradiotherapy for
      HNSCC. CONCLUSIONS: Further studies are needed to quantify the reliability of PET
      in detecting nodal residual disease after chemoradiotherapy for locoregionally
      advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains
      to be defined.

PMID- 21864254
TI  - Microneedles as transdermal delivery systems: combination with other enhancing
      strategies.
AB  - Transdermal drug delivery has exhaustively been studied over the past decades due
      to its multiple advantages over other administration routes; however, drugs that
      can be administered by this via are few owe to the stratum corneum permeability
      properties. Recently, several strategies to bypass the upper-layer skin barrier
      have been developed. One of the latest advances in this area has been the use of
      micro-scale needles, which painlessly pierce skin, increasing the passage of
      drugs with unfavourable skin permeability (i.e., low potent, hydrophilic, high
      molecular drugs) by several orders of magnitude, by bypassing the stratum
      corneum. Microneedles have shown to be safe and easy-to-use for drug
      administration, a nouvelle alternative to hypodermic needle injections, and an
      array in which drugs can be included to attain a controlled release as to achieve
      a higher drug delivery. Several works have demonstrated that such devices
      dramatically increase transdermal delivery of large molecules, thus nowadays
      microneedles have been regarded as a potential technology approach to be employed
      alone or with other enhancing methods such as electroporation and iontophoresis,
      as well as with different drug carriers (e.g., lipid vesicles, micro- and
      nanoparticles). Hence, this review is mainly focused on presenting the results
      obtained when combining microneedles with a variety of strategies to ease drug
      diffusion through skin, including physical enhancers and drug carrier systems.

PMID- 21864249
TI  - Vascular effects of estrogenic menopausal hormone therapy.
AB  - Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post
      MW) than premenopausal women (Pre-MW). Despite recent advances in preventive
      measures, the incidence of CVD in women has shown a rise that matched the
      increase in the Post-MW population. The increased incidence of CVD in Post-MW has
      been related to the decline in estrogen levels, and hence suggested vascular
      benefits of endogenous estrogen. Experimental studies have identified estrogen
      receptor ERalpha, ERbeta and a novel estrogen binding membrane protein GPR30
      (GPER) in blood vessels of humans and experimental animals. The interaction of
      estrogen with vascular ERs mediates both genomic and non-genomic effects.
      Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide,
      prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms
      of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C
      and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton,
      extracellular matrix, lipid profile and the vascular inflammatory response have
      been reported. In addition to the experimental evidence in animal models and
      vascular cells, initial observational studies in women using menopausal hormonal
      therapy (MHT) have suggested that estrogen may protect against CVD. However,
      randomized clinical trials (RCTs) such as the Heart and Estrogen/ progestin
      Replacement Study (HERS) and the Women's Health Initiative (WHI), which examined
      the effects of conjugated equine estrogens (CEE) in older women with established
      CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular
      effects of estrogen treatment. Despite the initial set-back from the results of
      MHT RCTs, growing evidence now supports the 'timing hypothesis', which suggests
      that MHT could increase the risk of CVD if started late after menopause, but may
      produce beneficial cardiovascular effects in younger women during the
      perimenopausal period. The choice of an appropriate MHT dose, route of
      administration, and estrogen/progestin combination could maximize the vascular
      benefits of MHT and minimize other adverse effects, especially if given within a
      reasonably short time after menopause to women that seek MHT for the relief of
      menopausal symptoms.

PMID- 21864255
TI  - Acne and its treatment options: a review.
AB  - Acne vulgaris is an extremely common condition affecting more than 80-90% of
      adolescents and young adults. It typically starts in late childhood or early
      teens, but onset may be delayed in some people well into their 20s and 30s. The
      incidence rate of acne is roughly the same in males and females but, males tend
      to have more serious conditions. Common therapies that are used for the treatment
      of acne include topical, systemic, herbal and combination therapies. This review
      is an attempt to trace out the causes of acne, to know its treatment options and
      precautions to be taken to prevent it.

PMID- 21864257
TI  - Freeze dried chitosan/ poly-(glutamic acid) microparticles for intestinal
      delivery of lansoprazole.
AB  - Lansoprazole sodium is a proton pump inhibitor used in treating gastroesophageal
      reflux disease (GERD). It is highly acid-labile and presents many formulation
      challenges. Therefore, this drug needs to be protected from the harsh environment
      in the stomach. In order to achieve this, a pH-sensitive microparticle system
      composed of chitosan and gamma- poly-(glutamic acid) was prepared and loaded with
      Lansoprazole. The prepared microparticles were not stable in gastric pH. To
      overcome this problem microparticles were freez-dried and filled in an enteric
      coated capsule. Upon oral administration, the enteric-coated capsule remained
      intact in the acidic environment of the stomach, but dissolved rapidly in the
      distal segment of the GIT. Consequently, all the microparticles loaded in the
      capsule were brought into the intestine, thus enhancing the intestinal absorption
      of drug. Drug encapsulation efficiency of formulation F3 was found to be 82.82 %
      and in vitro release of prepared formulation F3 was found to be 94% after 8 h of
      dissolution in 7.4 pH phosphate buffer. FTIR and DSC studies showed no
      interaction between the drug and polymer. The formulation showed good swelling
      property. SEM photographs showed that microparticles are spherical and lies in
      size range of 300-400 MUm. From the above, it can be concluded that the prepared
      chitosan/ gamma-poly-(glutamic acid) microparticles can be used as carriers for
      the intestinal delivery of acid liable drugs such as lansoprazole.

PMID- 21864256
TI  - The release and induced immune responses of a plant-made and delivered antigen in
      the mouse gut.
AB  - This study investigated the site of release of a model vaccine antigen from plant
      cells and the corresponding induced immune response. Three plant tissues (leaf,
      fruit and hairy root) and two formulations (aqueous and lipid) were compared in
      two mouse trials. A developed technique that enabled detection of antigen release
      by plant cells determined that antigen release occurred at early sites of the
      gastrointestinal tract when delivered in leaf material and at later sites when
      delivered in hairy roots. Lipid formulations delayed antigen release from all
      plant materials tested. While encapsulation in the plant cell provided some
      protection of the antigen in the gastrointestinal tract and influenced antigen
      release, formulation medium was also an important consideration with regard to
      vaccine delivery and immunogenicity. Systemic immune responses induced from the
      orally delivered vaccine benefited from late release of antigen in the mouse
      gastrointestinal tract. The influences to the mucosal immune response induced by
      these vaccines were too complex to be determined by studies performed here with
      no clear trend regarding plant tissue site of release or formulation medium.
      Expression and delivery of the model antigen in plant material prepared in an
      aqueous formulation provided the optimal systemic and mucosal, antigen-specific
      immune responses.

PMID- 21864258
TI  - Synthesis and characterization of pH-sensitive silica nanoparticles for oral
      insulin delivery.
AB  - The objective of this study is to utilize the pH sensitivity of modified
      mesoporous silica nanoparticles (MSN) for oral delivery of insulin. Activated
      silica nanoparticle was modified first with different densities of 3-
      Chloropropyltrimethoxysilane (3-CTMS) to load the Chlor group which will bond
      with the organic functional group contained in 4-hydroxybenzoic acid (4-HBA). The
      nanoparticles were characterized by FTIR and SEM. Equilibrium swelling studies
      were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and
      SIF, respectively). Insulin was entrapped in these nanoparticles and the in vitro
      release profiles were established separately in both (SGF, pH 1) and (SIF, pH
      7.4). The amount of loading of insulin was increased with increasing -COO-
      densities resulting from the increasing number of 4-HBA groups. In these cases,
      the biological activity of insulin was retained. These results were used to
      design and improve protein release behavior from these carriers.

PMID- 21864259
TI  - Anti-arthritic effects of immunomodulatory peptide injected in joints.
AB  - OBJECTIVE: To examine the clinical and histological outcomes following intra
      articular injection of an immunomodulatory peptide (CP) during an acute attack of
      adjuvant induced arthritis in rats. METHODS: Arthritis in rats was induced by
      injecting 0.1 mL of Mycobacterium Tuberculosis (MTB; 10mg/ml) intra-dermally at
      the base of the tail. After the onset of arthritis, affected ankle joints were
      injected with either 20 MUl of water, dexamethasone (4 mg/ml), cyclosporine (0.38
      mg; equivalent to 3mg/kg in humans), CP (60 mg/ml; 12.5 mg/ml; 6.25 mg/ml; 3.125
      mg/ml) or a CP analogue (CPD; 6.25mg/ml). There were a minimum of 5 rats/group
      and intra-articular injection was given on two separate occasions following the
      onset of arthritis. Rat weight, paw thickness, paw-width, ankle width and
      arthritic joint count were measured. Affected joints were X-rayed and joint
      tissue taken for histology. RESULTS: Rats given dexamethasone and cyclosporine
      had a significant improvement in clinical outcomes compared to the control group.
      CP at the highest dose was significantly better compared to the water group and
      the clinical effects were dose dependent. Histology of the joints showed severe
      inflammation and destruction in the water treated group with minimal inflammatory
      effects in the dexamethasone and cyclosporine group. Joints injected with
      cyclosporine were characterized by extensive fibrosis. The joints from CP treated
      rats showed mild to moderate inflammation with histological features somewhere
      between the cyclosporine and water injected groups. CONCLUSION: This study
      demonstrates that CP given intra-articularly has antiarthritic effects and raises
      new possibilities for treatment.

PMID- 21864260
TI  - New prospects for treatment of autoimmune diseases.

PMID- 21864261
TI  - Clinical update on the use of immuno modulators (antiCD3, GAD, Diapep277, anti
      IL1) in type 1 diabetes.
AB  - In type 1 diabetes, beta cells are attacked and destroyed by auto reactive T
      cells causing major impairment of blood glucose metabolism and, ultimately, the
      development of life-threatening complications. Currently, the treatment of this
      chronic disease is based on the use of endogenous insulin and no curative
      therapies are available. Treatment approaches in this respect need to be directed
      toward the primary causes of the disease tackling beta cells' auto reactive T
      cells. The goal of any curative intervention in type 1 diabetes is the
      preservation of insulin-secreting cells. This may be achieved by the abrogation
      of the pathogenic reactivity to beta cell auto antigens while preserving full
      capacity to generate a normal immune response against foreign antigens. In this
      review, some of the most promising drugs for immune intervention in type 1
      diabetes are presented and discussed including phase 3 clinical trials that
      involve: DiaPep277, Anti-CD3 Otelixizumab, Glutamic Acid Decarboxylase (GAD) and
      anti-IL1 receptor antagonist. These approaches are currently being tested in
      international multicenter trials and all of them have a very similar outcome in
      terms of a beneficial effect on beta cells.

PMID- 21864262
TI  - Update on intravenous immunoglobulins (IVIg) mechanisms of action and off- label
      use in autoimmune diseases.
AB  - Intravenous Immunoglobulins (IVIg) are administered both as replacement therapy
      for certain immunodeficiencies and as immunomodulatory therapy for some
      autoimmune diseases. While the treatment with IVIg is approved in only a few
      autoimmune diseases, the number of off-label indications is increasing. The
      varied mechanisms by which IVIg attains its beneficial effect are diverse. There
      is much evidence for the beneficial and safety profile for IVIg in low as well as
      high-dose protocols. Patients prone to develop thrombotic events should be
      advised about the risk of IVIg therapy especially at high doses. This paper
      updates the mechanisms of action of IVIg as well as recent off-label indications.

PMID- 21864263
TI  - Anti-TNF treatment in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized
      by persistent synovitis and systemic inflammation. Genetic predisposition as well
      as autoantibodies and environmental factors, such as smoking, are associated with
      an increased risk of RA. Traditionally RA has been treated with disease modifying
      anti-rheumatic drugs (DMARDs) but in the last 15 years or so the introduction of
      biological response modifiers has revolutionized the treatment of RA. Among these
      anti-tumor necrosis factor (TNF) agents were the first to be successfully used in
      treating RA. The goal in treating RA is to induce remission or very low disease
      activity; remission is now accepted as the ultimate therapeutic goal by adoption
      of a "treat to target" strategy to achieve tight disease control. Therefore early
      diagnosis, as well as immediate intervention, are of the utmost importance. This
      review of the role of TNF in RA pathogenesis describes the mechanisms of action
      of currently used anti-TNF agents and the adverse events and safety of these
      drugs. Guidance on the use of anti-TNFs during pregnancy and prior to surgical
      procedures is also discussed. The intense efforts currently being made to
      identify biomarkers of response to anti-TNF therapy and recent progress in
      defining genetic predictors of response using genome- wide association studies
      (GWAS) are covered. However, so far, none of these studies have been translated
      into clinical application. The development of biosimilars or follow-on
      biologicals is also discussed and the first reported study of a biosimilar,
      involving a multicenter study of an etanercept biosimilar, Etanar, is described.

PMID- 21864264
TI  - Immunotherapy-based strategies for the treatment of autoimmune diabetes:
      searching for the cure.
AB  - Type 1 Diabetes is an autoimmune disease most often associated with elevated and
      uncontrolled blood glucose levels. Therefore patient education and treatment
      compliance is often focused on disease maintenance through insulin treatment and
      blood glucose control. Unfortunately insulin therapy alone does not prevent the
      formation of diabetic complications. In order to find a real cure, the underlying
      pathology of the disease must be directly addressed. Diabetes is caused by the
      initial rapid destruction of the insulin producing beta cells of the pancreas by
      autoreactive T-cells. The autoimmune process is also maintained through dendritic
      cell auto-antigen presentation and the production of autoantibodies by B cells.
      Only through some forms of immunotherapy can the immune system be rebalanced to
      assure the survival of the remaining beta cell population. These techniques
      include cell ablation, competitive decoy auto-antigens, reduced cell activation,
      and auto-antigen introduction. Here we will review the current state of these
      different technologies and their progression through clinical trials for the
      treatment of type 1 diabetes.

PMID- 21864265
TI  - B cell modulation strategies in autoimmunity: the SLE example.
AB  - The paradigm that T cells are the prime effectors of autoimmune diseases has been
      recently challenged by growing evidence that B-lymphocytes play a role in the
      development, re-activation and persistence of autoimmune disorders. B-cells of
      different subsets may play different roles in autoimmune pathologies due to their
      ability to secrete antibodies, produce cytokines, present antigen and form
      ectopic germinal centers. Thus, a given therapeutic approach or drug may have
      distinct outcomes depending on which specific B cell subset is targeted.
      Immunosuppressive therapies such as azathioprine (AZA), cyclophosphamide (CyC) or
      methotrexate (MTX) are conventionally used in autoimmune diseases with the aim of
      reducing disease activity and improving the patient's general health conditions.
      These treatments do not target a specific cellular type or subset and have
      substantial side effects, such as impairment of liver function and fertility.
      Moreover, autoimmune patients may be refractory to immunosuppressive therapy. In
      these cases finding an effective treatment becomes a challenge. The fast
      evolution in antibody technology is leading to the production of a wide array of
      humanized monoclonal antibodies, targeting specific cell types or pathways,
      initiating a new era in the treatment of autoimmune disorders. In addition, the
      recent discovery that toll like receptors (TLRs) activation can fire up
      autoimmunity in humans and maintain disease gives the grounds for the development
      of new drugs targeting the TLR/MyD88 pathway. In contrast to conventional immune
      suppression, the availability of drugs interfering with B-cell specific
      pathogenetic pathways gives the possibility to choose therapies tailored to each
      disease and, possibly, to each patient.

PMID- 21864266
TI  - The chemokine system as a therapeutic target in autoimmune thyroid diseases: a
      focus on the interferon-gamma inducible chemokines and their receptor.
AB  - The recruitment, trafficking, and in situ maintenance of specific subsets of
      activated lymphocytes constitute crucial steps for the initiation and
      perpetuation of chronic autoimmune inflammation. The fact that, after IFN-gamma
      stimulation, thyrocytes secrete CXCR3- binding chemokines, which in turn recruits
      Th1 lymphocytes expressing CXCR3 and secreting IFN-gamma, strongly supports the
      concept that the interferon-gamma inducible chemokines (CXCL9, CXCL10, and
      CXCL11) and their receptor CXCR3 play an important role in the initiation of
      autoimmune thyroid diseases (AITD). Thus, interfering with CXCR3 might result in
      the abrogation of the inflammatory process. The understanding of these
      pathogenetic mechanisms suggested novel therapeutic approaches, with a growing
      interest for finding a way to interrupt the interactions between chemokines and
      their receptors. In this review, we focus on the efforts performed in
      establishing new pharmacological compounds able to target the chemokine/chemokine
      receptors system as well as to prevent the secretion of CXCR3-binding chemokines,
      induced by pro-inflammatory cytokines. The crucial issue of selecting the
      relevant therapeutic targets in animal models of AITD was also discussed.
      Although some encouraging results have been reached, major hurdles were
      encountered on the way to success. As a result, we are still waiting for the
      first anti-chemokine anti-inflammatory drug. Given the importance of leukocytes
      recruitment to inflammatory sites, research will continue to address the issue of
      developing specific chemokine-receptor antagonists. We look forward to the
      development of these novel pharmacological compounds which will hopefully provide
      a more valid alternative to the currently used lifelong replacement therapies for
      AITD.

PMID- 21864267
TI  - Experimental strategies in autoimmunity: antagonists of cytokines and their
      receptors, nanocarriers, inhibitors of immunoproteasome, leukocyte migration and
      protein kinases.
AB  - Autoimmune diseases are a heterogeneous group of disorders and epidemiological
      studies demonstrate that their incidence is increasing worldwide. It is known
      that a complex interaction of genetic and environmental factors underlies their
      complex etiopathogenesis. In the light of the aforegoing the exact molecular key
      events were difficult to be explored; these represent the leading step to the
      prevention and treatment of autoimmune disorders. Novel therapeutic approaches
      are nowadays under investigation and specific treatments have been preferentially
      applied in experimental models of disease. New results were brought about and
      fascinating new pathways for treatment of autoimmunity were launched in the past
      years. Nevertheless novel targets for intervention, revealed to be successful in
      animal models, were not necessarily proven to be successful in humans, therefore
      were not necessarily introduced in clinical trials. In this review we present and
      discuss the results of novel therapeutic approaches and novel experimental
      strategies including antagonists of cytokines and cytokine receptors, Toll like
      receptors inhibitors, proteasome inhibitors, antisense oligonucleotides vehicled
      by nanocarriers, inhibitors of leukocyte migration, kinase inhibitors. We also
      present the results of ongoing trials in humans that rely on novel biologicals
      agents. These are presented as applied to organ and non-organ specific autoimmune
      disorders. In the future, novel therapeutic strategies will also combine
      different drugs that possibly intervene at different levels in which the immune
      system may be halted in its function.

PMID- 21864268
TI  - A pathogenetic approach to autoimmune skin disease therapy: psoriasis and
      biological drugs, unresolved issues, and future directions.
AB  - Psoriasis is a chronic inflammatory disease with a complex pathophysiology and a
      multigenic background. Autoimmunity and genetic hallmarks couple to confer the
      disease, which is characterized by chronic plaques (85-90% of all cases) and/or
      psoriasis arthritis (PsA), and involve the peripheral and sacro-iliac joints,
      nails, and skeleton. Dissecting the ethiopathogenetic mechanisms of psoriasis and
      PsA is a major basic research challenge. One important question is whether a
      single inflammatory mediator can be responsible for the interactive network that
      forms between immune cells and cytokines in this disease. Despite much progress,
      no research has yet been able to define a single model to explain the
      multifaceted pathogenesis of psoriasis and PsA. It is known that both the innate
      and adaptive immune systems are involved, antigen presenting cells and T
      lymphocytes play a prominent role, and that the deregulation of the T helper (Th)
      1/Th-2/Th-17/Th-23 axis is directly implicated in disease pathogenesis.
      Pharmacological therapy for psoriasis has evolved with the development of human
      knowledge of the disease pathophysiology. Thus, the first "ethiopathogenetic"
      drugs (e.g., methotrexate, cyclosporin, and alefacept) inhibited T-cell
      activation directly or targeted co-accessory molecules implicated in T-cell
      activation. When the mechanism underlying psoriatic inflammation was accepted as
      a cytokine network disorder, more specific biologics were studied in murine
      models and were later used clinically. Tumor necrosis factor was the first
      successful target of cytokine inhibition therapy for psoriasis and PsA (e.g.,
      infliximab, adalimumab, and etanercept). With the recently discovered role for Th
      17 in autoimmunity, drugs targeting interleukin-23 (ustekinumab) have become
      accepted for the pharmacological treatment of psoriasis. The expansion of
      pharmacological treatment options for psoriasis is not complete. As the knowledge
      of pathogenetic mechanisms increases, it may be possible to design therapeutic
      approaches that selectively target the ethiopathogenetic cells or cytokines while
      sparing the others. In this way, using a more targeted drug therapy may preserve
      the integrity of the immune system. Thus, one great struggle in treating this
      complex disease is the challenge to synthesize the "perfect" drug.

PMID- 21864269
TI  - Manipulating thymic apoptosis for future therapy of autoimmune diseases.
AB  - In humans, T-cell development takes place in the thymus, which contains an
      external cortical region and an inner medulla. The skeleton of the thymus
      consists of stromal cells and is filled with thymocytes in different stages of
      differentiation. Thymocytes undergo to a development process before becoming
      mature T lymphocytes ready for export to the peripheral lymphoid organs.
      Classically, T-cell development has been reported to occur in four steps. First,
      bone marrow derived thymocytes that express neither CD4 nor CD8 surface antigens
      (double negative [DN] thymocytes) undergo an extensive phase of proliferation and
      differentiation and begin to express CD4 and CD8 (step 2: double positive [DP]
      thymocytes). During a subsequent negative selection process, approximately 5% of
      these DP cells undergo apoptosis. If these cells are not eliminated, they could
      differentiate into autoreactive lymphocytes, leading to the development of
      peripheral autoimmune diseases. In the thymus, a particular population of T
      regulatory (Treg) cells also develops. These Treg cells migrate to the periphery
      and are capable of suppressing autoreactive lymphocytes that may have escaped
      from the negative selection process. Autoimmune diseases are generally the result
      of insufficient negative selection of autoreactive cells in the thymus or a
      deficiency in Treg cell production or function. Future therapeutic strategies for
      autoimmune diseases should exploit manipulations in the negative selection
      process and/or the differentiation of Treg cells in the thymus.

PMID- 21864270
TI  - Novel therapeutic approaches to autoimmune demyelinating disorders.
AB  - Multiple Sclerosis (MS) is the most common autoimmune demyelinating disorder in
      Western countries and can lead to permanent disability. Over the past decades
      remarkable progress has been made in providing new therapeutic strategies to
      tackle the burden of the disease. Oral drugs and monoclonal antibodies are the
      main innovative approaches that have been tested in advanced stage clinical
      trials. Several new drugs have been shown to be superior to traditional disease
      modifying treatments (DMTs), in terms of both clinical and imaging outcome
      measures. Oral drugs have the advantage of offering a convenient route of
      administration. Recently fingolimod has received approval for the treatment of
      relapsing remitting (RR)-MS in several countries, becoming the first oral drug
      available to patients. Whilst the majority of the current studies focus on RR-MS,
      some trials investigate the primary or secondary progressive subtypes as well as
      the early forms of the disease aiming at delaying the conversion to clinically
      definite MS. Overall the future of the treatment options looks promising,
      although the occurrence of significant adverse events in some instances points to
      cautious evaluation of risks and benefits. Extension studies for most of the new
      drugs are under way and will provide evidence on the efficacy and long term
      effects of the new treatment strategies.

PMID- 21864271
TI  - Stem cell-based immunomodulation in type 1 diabetes: beyond the regenerative
      approach.
AB  - Type 1 diabetes (T1D) is an autoimmune disease, leading to pancreatic beta-cell
      destruction and loss of glycaemic control. Administration of exogenous insulin to
      diabetic patients prevents life-threatening metabolic derangement, but may fail
      to prevent other longterm complications, such as kidney failure or diabetic
      retinopathy. Islet transplantation is a low-risk surgical procedure, affording
      improved glucose homeostasis provided sufficient islets engraft in the liver.
      Here we review work on the use of stem cells to generate beta- cells for islet
      transplantation, indicating the need for improved protocols for their derivation
      and full maturation. We also consider recent evidence indicating that adult
      stem/progenitor cells may affect islet transplantation by improving the viability
      of engrafted islets and controlling immune reactions to islet allo- and auto
      antigens, extending stem-cell use in T1D beyond the regenerative approach.

PMID- 21864272
TI  - The pathology and immunology of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a pruritic chronic inflammatory disease of the skin
      that is triggered by an underlying complicated interplay between the genetics of
      the individual and stimulation by allergens. Patients with AD demonstrate
      compromised barrier function that leads to activation of keratinocytes and immune
      cells which favor a strong Th2 bias. As a result of this immunological bias such
      patients also suffer from secondary pathogenic infections. A wide array of
      cytokines and chemokines interact to yield symptoms characteristic of AD. In
      addition, the involvement of different immunological cell types compounds our
      difficulty in understanding its immunopathogenesis. The use of various mouse
      models and transgenics has allowed us to intricately examine the functioning of
      the various molecules identified to play a role in AD. Such mouse models have
      also aided in the testing and development of various therapeutics for AD. This
      review is focused on examining the various factors contributing to the
      pathogenesis and exacerbation of AD as well as current treatments for AD. There
      is scope for improving the therapy of AD patients and thereby allowing them a
      better quality of life.

PMID- 21864273
TI  - Impact of sphingosine kinase on inflammatory pathways in fibroblast-like
      synoviocytes.
AB  - Sphingolipids are mediators of inflammation; changes in their cellular
      concentration modulate specific cellular functions. Investigations of sphingosine
      kinases (SphK) and sphingosine 1 phosphate (S1P) in TNFalpha driven murine models
      of rheumatoid arthritis (RA), identified SphK/S1P as important intermediaries in
      TNFalpha mediated synovial proinflammatory pathways. Fibroblast-like synoviocytes
      (FLS) are key contributors to RA pathogenesis and express both SphK 1 and 2. To
      pinpoint the mechanisms of SphK effects in the inflammatory response of murine
      FLS in vitro, we derived SphK1 null (SphK1-/-) FLS and SphK1 wild-type (SphK1+/+)
      FLS from the knee joints of B6 mice. Significantly less MMP1a and IL-6 were
      produced by mTNFalpha-stimulated SphK1-/- FLS versus SphK1+/+ FLS. Trends toward
      less PGE2 as well as activated, ERK 1/2 and STAT3 were present in SphK1-/- FLS
      versus SphK1+/+ FLS. Thus genetic inhibition of SphK1 activity resulted in
      decreased expression of inflammatory mediators and decreased activation of
      inflammatory pathways in TNFalpha stimulated murine FLS. This decreased
      inflammatory phenotype in FLS lacking SphK1 activity is consistent with the
      attenuated TNF-alpha-driven arthritis in vivo in SphK1 deficient mice and adds to
      the understanding of the mechanistic role of SpK1/S1P in rheumatoid arthritis.
      Thus, specific therapeutic can be targeted with SphK inhibitors in rheumatoid
      arthritis.

PMID- 21864274
TI  - Targeting the F1Fo ATP Synthase: modulation of the body's powerhouse and its
      implications for human disease.
AB  - Throughout our lifetime the F1Fo ATP synthase produces the majority of our
      biological energy, and plays central roles in the structure and organization of
      mitochondria, yet our understanding of its roles in human disease remain largely
      enigmatic. It seems logical that even intermittent impairment of this highly
      important enzyme could deprive the body's tissues of energy at crucial times,
      which may predispose or contribute to illness. Indeed, evidence is accumulating
      that there are dire consequences of energy depletion in acute lifethreatening
      conditions, such as heart attacks, as well as chronic diseases, including aging,
      cancer, diabetes and heart failure. Recent advances in our understanding of the
      expanding roles of F1Fo ATP synthase, and how it is regulated, combined with the
      development of novel strategies for manipulating its function, may provide
      renewed hope for therapeutic improvement of energy homeostasis, and mitochondrial
      integrity, in a host of human diseases. In this review we will highlight what is
      known about the molecular regulation of this amazing enzyme complex, discuss
      effects of physiological agonists and therapeutic drugs on its functions, and
      present evidence supporting its involvement in the ills of mankind. Finally, we
      will outline existing challenges, and promising new avenues for targeting the
      enzyme therapeutically.

PMID- 21864275
TI  - Templates and models of monoamine transporter proteins.
AB  - X-ray crystallography, structural bioinformatics and computational chemistry have
      become important techniques in the discovery and development of effective and
      safe new drugs. From a drug discovery point of view, membrane proteins are among
      the most interesting molecular targets, but the current knowledge about detailed
      3D structures of membrane proteins is sparse. Homology modeling techniques may
      provide structural knowledge about membrane proteins and their interactions with
      drugs and other molecules. The neurotransmitter sodium symporters (NSS) are the
      molecular targets of many pharmacologically active substances, and we have used
      three different secondary transporters as templates for modeling the NSS proteins
      DAT, NET and SERT. The first template was based on the electron density
      projection map of the Escherichia coli Na+/H+ antiporter (NhaA), while later the
      X-ray structure of Lac Permease (symporter) was used as a template. The helical
      architectures of these templates have a lot in common, and models based on both
      could contribute with structural explanations of several experimental studies in
      spite of low homology with NSS proteins. In 2005 the crystal structure of a
      bacterial homologue of the human monoamine neurotransmitter transporter Aquifex
      aeolicus (LeuTAa) was reported. This structure was the first experimental
      structure of a NSS family member, and represented a breakthrough for homology
      modeling of pharmacological important NSS proteins. Since then several X-ray
      structures LeuTAa in complex with pharmacologically important compounds have been
      published. Homology models of NSS proteins, combined with site-directed
      mutagenesis data, have identified ligand binding sites and contributed with
      important knowledge for new drug development.

PMID- 21864277
TI  - Clinical trial update and novel therapeutic approaches for metastatic prostate
      cancer.
AB  - Recurrent prostate cancer (PCa) remains a major clinical challenge. Invasive and
      metastatic PCa lesions often exhibit a partial and time-limited response to
      therapy before the cancer progresses and the patient succumbs to the disease.
      Despite recent advances in early diagnosis and treatment, approximately one-third
      of treated patients will relapse and become resistant to currently available
      treatments. In this review we evaluate current treatment practices and recent
      advances in therapy for localized prostate malignancy and advanced, metastatic
      prostate cancer. Some of the promising new drugs for PCa treatment include
      MDV3100, an androgen receptor (AR) antagonist that prevents androgens from
      binding to the AR and nuclear translocation and co-activator recruitment of the
      ligand-receptor complex; abiraterone, an orally administered drug that
      irreversibly inhibits a rate-limiting enzyme in androgen biosynthesis, CYP17; and
      several newer cytotoxic drugs (epothilones, satraplatin). Key new insights are
      that cancer stem cells play a role in PCa and that PCa cells are dependent on the
      AR for proliferation, even in the hormone refractory state of the disease. We
      also discuss potential molecular targets for new drug candidates for the
      treatment of metastatic PCa.

PMID- 21864278
TI  - Mitochondrial alterations and neuropsychiatric disorders.
AB  - Mitochondria are membrane-enclosed organelle found in most eukaryotic cells,
      where they generate the majority of the cell's supply of adenosine triphosphate
      (ATP), used as a source of chemical energy. In addition, they are involved in a
      range of other processes, such as signalling, cellular differentiation, cell
      death, as well as the control of the cell cycle and cell growth. Mitochondria
      have been implicated in several neuropsychiatric disorders, in particular,
      depression, anxiety, schizophrenia, autism, and Alzheimer's dementia.
      Furthermore, the presence of mutations at the level of mitochondrial or nuclear
      DNA (mtDNA and nDNA, respectively) has been linked to personality disorders,
      behavioral disturbances, thought alterations, impulsivity, learning impairment,
      cognitive failures until dementia. The aim of this paper is to review the
      literature on the relationship between psychiatric symptoms or syndromes and
      mtDNA mutations or mitochondrial alterations, while highlighting novel
      therapeutic targets for a broad range of disorders.

PMID- 21864276
TI  - A structure-function perspective of Jak2 mutations and implications for alternate
      drug design strategies: the road not taken.
AB  - Jak2 is a non-receptor tyrosine kinase that is involved in the control of
      cellular growth and proliferation. Due to its significant role in hematopoiesis,
      Jak2 is a frequent target for mutations in cancer, especially myeloid leukemia,
      lymphoid leukemia and the myeloproliferative neoplasms (MPN). These mutations are
      common amongst different populations all over the world and there is a great deal
      of effort to develop therapeutic drugs for the affected patients. Jak2 mutations,
      whether they are point, deletion, or gene fusion, most commonly result in
      constitutive kinase activation. Here, we explore the structure-function relation
      of various Jak2 mutations identified in cancer and understand how they disrupt
      Jak2 regulation. Current Jak2 inhibitors target the highly conserved active site
      in the kinase domain and therefore, these inhibitors may lack specificity. Based
      on our knowledge regarding structure-function correlations as they pertain to
      regulation of Jak2 kinase activity, an alternative approach for specific Jak2
      targeting could be via allosteric inhibitor design. Successful reports of
      allosteric inhibitors developed against other kinases provide precedent for the
      development of Jak2 allosteric inhibitors. Here, we suggest plausible target
      sites in the Jak2 structure for allosteric inhibition. Such targets include the
      type II inhibitor pocket and substrate binding site in the kinase domain, the
      kinase-pseudokinase domain interface, SH2-JH2 linker region and the FERM domain.
      Thus, future Jak2 inhibitors that target these sites via allosteric mechanisms
      may provide alternative therapeutic strategies to existing ATP competitive
      inhibitors.

PMID- 21864279
TI  - Recent developments of peptidomimetic HIV-1 protease inhibitors.
AB  - HIV protease plays a crucial role in the viral life cycle by processing the viral
      Gag and Gag-Pol polyproteins into structural and functional proteins essential
      for viral maturation. Inhibition of HIV-1 protease leads to the production of
      noninfectious virus particles and hence is an important therapeutic target for
      antiviral therapy in AIDS patients. Among many strategies to combat this disease,
      highly active antiretroviral therapy (HAART) with HIV protease inhibitors (PIs)
      in combination with reverse transcriptase inhibitors and fusion inhibitor
      continues to be the first line treatment for control of HIV infection. However,
      the rapid emergence of drug-resistant HIV-1 strains and the appearance of cross
      resistance are severely limiting the long-term treatment options. Thus, numerous
      efforts have been made in the design and synthesis of novel protease inhibitors
      with broad-spectrum activity against multidrug-resistant HIV-1 variants by
      medicinal chemists. This review will focus on the substrate-based drug design of
      novel peptidomimetic PIs in recent years since 2006.

PMID- 21864280
TI  - Oligomerization of G protein-coupled receptors: biochemical and biophysical
      methods.
AB  - Dimerization and oligomerization of G protein-coupled receptors (GPCRs), proposed
      almost 30 years ago, have crucial relevance for drug design. Indeed, formation of
      GPCR oligomers may affect the diversity and performance by which extracellular
      signals are transferred to G proteins in the process of receptor transduction.
      Thus, the control of oligomer assembly/disassembly and signaling will be a
      powerful pharmacological tool. This, however, requires (i) the determination that
      oligomerization takes place between particular receptors, (ii) the confirmation
      that the oligomer has pharmacological importance and (iii) the availability of
      the oligomer 3D structure. This review aims at presenting experimental methods
      which unveil the complexity of GPCR dimerization/oligomerization focusing on
      biochemical and biophysical approaches. In total, we review 22 methods, including
      biochemical methods (radiation inactivation technique, receptor co-expression and
      trans-complementation studies, cross-linking experiments, co-immunoprecipitation
      and immunoblotting studies and analysis of receptor mutants and chimeras) and
      biophysical methods (Fluorescence Resonance Energy Transfer, (FRET), including
      photobleaching FRET (pb-FRET) and Time-Resolved FRET (TR-FRET), Luminescence
      Resonance Energy Transfer (LRET), Bioluminescence Resonance Energy Transfer
      (BRET), Bimolecular Fluorescence Complementation (BiFC), Luminescence
      Fluorescence Complementation (BiLC), Fluorescence Recovery after Photobleaching
      (FRAP), Confocal Microscopy, Immunofluorescence Microscopy, Single Fluorescent
      Molecule Imaging, Transmission Electron Microscopy, Immunoelectron Microscopy,
      Atomic Force Microscopy, Total Internal Reflectance Fluorescence Microscopy
      (TIRFM) and X-ray Crystallography). For each method the scientific basis of the
      approach is shortly described followed by the extensive description of its
      application for studying GPCR oligomers presented according to their classes and
      families. Based on the wealth of experimental evidence, there is no doubt about
      the existence of GPCR dimers, oligomers and receptor mosaics which constitute a
      new and highly promising group of novel drug targets for more selective and safer
      drugs.

PMID- 21864281
TI  - Oligomerization of G protein-coupled receptors: computational methods.
AB  - Recent research has unveiled the complexity of mechanisms involved in G protein
      coupled receptor (GPCR) functioning in which receptor
      dimerization/oligomerization may play an important role. Although the first high
      resolution X-ray structure for a likely functional chemokine receptor dimer has
      been deposited in the Protein Data Bank, the interactions and mechanisms of dimer
      formation are not yet fully understood. In this respect, computational methods
      play a key role for predicting accurate GPCR complexes. This review outlines
      computational approaches focusing on sequence- and structure-based methodologies
      as well as discusses their advantages and limitations. Sequence-based approaches
      that search for possible protein-protein interfaces in GPCR complexes have been
      applied with success in several studies, but did not yield always consistent
      results. Structure-based methodologies are a potent complement to sequence-based
      approaches. For instance, protein-protein docking is a valuable method especially
      when guided by experimental constraints. Some disadvantages like limited receptor
      flexibility and non-consideration of the membrane environment have to be taken
      into account. Molecular dynamics simulation can overcome these drawbacks giving a
      detailed description of conformational changes in a native-like membrane.
      Successful prediction of GPCR complexes using computational approaches combined
      with experimental efforts may help to understand the role of dimeric/oligomeric
      GPCR complexes for fine-tuning receptor signaling. Moreover, since such GPCR
      complexes have attracted interest as potential drug target for diverse diseases,
      unveiling molecular determinants of dimerization/oligomerization can provide
      important implications for drug discovery.

PMID- 21864282
TI  - Development of 5-Fluorouracil derivatives as anticancer agents.
AB  - 5-Fluorouracil (5-FU) is one of the most potent antimetabolites which have been
      widely used in the treatment of advanced solid tumors. As an anticancer agent,
      because of its low efficacy and high toxicity, numerous modifications of 5-FU
      structure have been performed. A great number of novel 5-FU derivatives have been
      developed with highly efficient and much less toxic. In this paper, the recent
      development of novel 5-FU derivatives as potent antitumor agents is reviewed and
      discussed.

PMID- 21864283
TI  - Phytosterols: perspectives in human nutrition and clinical therapy.
AB  - Phytosterols (PSs) are a group of plant derived steroid alcohols, with wide
      occurrence in vegetables and fruits. They are integral components of plant cell
      membranes, having stabilizing effects on phospholipids bilayer, just like
      cholesterol in animal cell membranes. Structural resemblance of PSs with
      cholesterol enables them to displace low-density lipoprotein (LDL) cholesterol in
      the human intestine. Protective effects of PSs against cardiovascular diseases
      (CVDs), colon and breast cancer developments have been widely documented. Several
      reports have been published on the potential dietary intake of common PSs, such
      as beta-sitosterol, stigmasterol and campesterol, and their safety concerns.
      Ability of PSs to reduce cholesterol levels and risks associated with heart
      problems has made them a class of favorite food supplements. Nowadays functional
      foods supplemented with PSs have become an alternative and healthy tool to lower
      LDL-cholesterol levels in a natural way. However, excessive use of PSs has been
      observed to develop premature coronary artery disease in phytosterolemic
      patients, high risk of atherosclerotic CVDs, myocardial infarction and even
      impaired endothelial functions. This manuscript will highlight the recent
      developments in PSs with particular focus on their role as dietary supplements
      and in treatment of various heart- and cholesterol-related ailments. Recently
      explored side effects of PSs will also be discussed.

PMID- 21864284
TI  - Selenium and clinical trials: new therapeutic evidence for multiple diseases.
AB  - The understanding of the essential role of selenium (Se) in human health has
      increased substantially in recent decades. Micronutrient deficiencies are very
      common in the general population and may be even more common in patients with
      different pathologies due to genetic or environmental causes and prescription
      drug use. Selenium is used by people in the prevention and/or treatment of
      different disorders including cardiovascular disease, osteoarthritis, rheumatoid
      arthritis, hypothyroidism, stroke, atherosclerosis, cancer susceptibility and
      treatment, HIV, AIDS, neuronal diseases such as Alzheimer or amyotrophic lateral
      sclerosis, pancreatitis, depression, and diabetes amongst others. Several
      mechanisms have been suggested to mediate the biological effects of Se and these
      include antioxidant defence systems, synthesis and stability of metabolites that
      act as intermediates implicated in diverse selenoproteins expression pathways
      oxidative metabolism, immune system modulation, DNA intercalators, kinase
      regulation, enzymatic cofactor, and gene expression. A number of clinical trials
      in recent years have provided convincing evidence of the central role of this
      element, either alone or in combination with other micronutrients or
      antioxidants, in the prevention and treatment of multiple diseases. Based on
      these studies this review focuses on the advances made so far in the study of
      mechanisms and applications of selenium compounds that could be suitable for
      chronic diseases.

PMID- 21864285
TI  - Squalene synthase inhibitors: An update on the search for new antihyperlipidemic
      and antiatherosclerotic agents.
AB  - Atherosclerosis and related heart disease is strongly associated with elevated
      blood levels of total (and LDL) cholesterol. Due to the widespread incidence as
      well as severity of this pathological condition, major efforts have been made for
      the discovery and development of hypocholesteroleamic agents. In the past few
      decades, HMG-CoA reductase inhibitors (statins) are being extensively used as
      lipid lowering drugs. These agents act predominantly by inhibiting the enzyme 3
      hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) that is the rate limiting
      step of cholesterol biosynthesis. Both the success as well as drawbacks of
      HMGRIs, have led to the investigation and design of inhibitors of other
      (downstream) enzymes involved in the multistep cholesterol biosynthetic pathway.
      One such class of agents consists of the squalene sythase inhibitors which act at
      the first and solely committed step towards the biosynthesis of the cholesterol
      nucleus. This target is considered not to interfere with the biosynthesis of
      other biologically important molecules and thus a better side-effect profile is
      expected for these inhibitors. Several classes of squalene synthase inhibitors
      (SQSIs), such as substrate or transition-state analogues, zaragozic acids or 2,8-
      dioxabicyclo[3.2.1]octane derivatives, dicarboxylic acid and quinuclidine
      derivatives, 4,1-benzoxazepine as well as substituted morpholine derivatives,
      have been studied as potent inhibitors of squalene synthase. So far only one
      benzoxazepine derivative (TAK-475) has been evaluated in advanced clinical
      trials. In this article we review the up to date research and literature on the
      therapeutic potential of this relatively new class of compounds, the drug
      discovery efforts towards the development of active squalene synthase inhibitors,
      their activity profile and effectiveness, as well as their structure-activity
      relationships.

PMID- 21864287
TI  - Functionalized graphene oxide as nanocarrier for loading and delivery of ellagic
      Acid.
AB  - In this research, we have covalently functionalized graphene oxide (GO) with
      hydrophilic and biocompatible Pluronic F38 (F38), Tween 80 (T80) and maltodextrin
      (MD) for loading and delivery of a poorly water soluble antioxidant and
      anticancer drug, ellagic acid (EA). The functionalized GO showed a good aqueous
      solubility and biocompatibility. This is the first time that the EA was loaded
      onto GO-F38, GO-T80 and GO-MD through pi-pi interactions, yielding a loading
      capacity of 1 g, 1.22 g and 1.14 g of EA per gram of GO-F38, GO-T80, and GO-MD
      respectively. Their capabilities to kill human breast carcinoma cells (MCF7) and
      human colon adenocarcinoma cells (HT29) were then investigated. The release of EA
      from these nanocarriers was studied in water (neutral pH) and buffer solutions of
      pH 4 and 10 at 37  degrees  C. The GO-F38, GO-T80 and GO-MD released ~ 36-38%
      drug within 3 days at pH 10. The cytotoxicity of EA loaded onto the
      functionalized GO was higher than that of free EA dissolved in DMSO. The DPPH
      assay was used to study the antioxidant activity, and the very similar
      antioxidant activities were obtained for three EA-loaded nanocarriers and the
      free EA, indicating that loading of EA onto the functionalized GO did not hamper
      its antioxidant activity. Therefore, all three functionalized GOs are suitable
      nanocarriers for drug delivery because of their non-toxicity and high drug
      loading capacity.

PMID- 21864288
TI  - The molecular basis for the pharmacological activity of anthocyans.
AB  - This review summarizes the current knowledge of the regulatory role of pure
      anthocyans in cellular signaling pathways and gene expression. The molecular
      basis for anthocyans pharmacological activity includes the regulation of plethora
      of mechanisms mainly involved in: (1) suppression of the inflammatory response
      through targeting the phospholipase A2 and PI3K/Akt and NF-kappaB pathways, (2)
      protection from cardiovascular disease by exerting (i) antihypertensive and
      endothelium-protective activity through targeting the Akt/eNOS and ACE pathways
      (ii) antiatherogenic activity through targeting NF-kappaB mediated VCAM and ICAM
      expression, (3) growth/differentiation control and tumor suppression by exerting
      (i) anticancerogenic activity through targeting the EGF and HGF signaling
      pathways (ii) tumor anti-invasive activity through targeting the VEGF signaling
      pathway and ECM degrading enzymes (iii) cell cycle arrest and induction of
      apoptosis through the JNK/p38 MAPK mediated caspase activation (iv) modulation of
      chemotherapeutic efficacy by affecting resistance to anticancer drugs, (4)
      reduction of diabetes incidence through modulation of insulin sensitivity and
      glucose utilization, (5) neuroprotection through amelioration of oxidative stress
      and Abeta deposition, and (6) hepatoprotective activity through interference with
      TNF-alpha and TGF-beta in the liver. The estrogen-like activity of anthocyans
      could be utilized in cancer and hormone-replacement therapy. These data provide a
      concise insight into molecular mechanisms of protective and therapeutic activity
      of anthocyans in various pathological conditions, which may not be attributed
      solely to their antioxidant activity but also to direct blockage of signaling
      pathways. Structure-activity analysis reveals that the number of hydroxyl groups
      and presence of sugar moiety are crucial for their specific modulatory actions.

PMID- 21864289
TI  - Targeting monoamine oxidases with multipotent ligands: an emerging strategy in
      the search of new drugs against neurodegenerative diseases.
AB  - The socioeconomic burden of multi-factorial pathologies, such as
      neurodegenerative diseases (NDs), is enormous worldwide. Unfortunately, no proven
      disease-modifying therapy is available yet and in most cases (e.g., Alzheimer's
      and Parkinson's disease) the approved drugs exert only palliative and symptomatic
      effects. Nowadays, an emerging strategy for the discovery of disease-modifying
      drugs is based on the multi-target directed ligand (MTDL) design, an innovative
      shift from the traditional approach one-drug-one-target to the more ambitious one
      drug-more-targets goal. Herein, we review the discovery strategy, the mechanism
      of action and the biopharmacological evaluation of multipotent ligands exhibiting
      monoamine oxidase (MAO) inhibition as the core activity with a potential for the
      treatment of NDs. In particular, MAO inhibitors exhibiting additional
      acetylcholinesterase (AChE) or nitric oxide synthase (NOS) inhibition, or ion
      chelation/antioxidant-radical scavenging/anti-inflammatory/A2A receptor
      antagonist/APP processing modulating activities have been thoroughly examined.

PMID- 21864290
TI  - Transposon-mediated gene transfer into adult and induced pluripotent stem cells.
AB  - Transposon technology is a particularly attractive non-viral gene delivery
      paradigm that allows for efficient genomic integration into a variety of
      different cell types. In particular, transposon-mediated gene transfer is a
      promising tool for stem cell research, by virtue of its ability to efficiently
      and stably transfer genes into adult and induced pluripotent stem (iPS) cells.
      Moreover, transposons open up new perspectives for non-viral-mediated stem cell
      based gene therapy. Several transposon systems, especially the Sleeping Beauty
      (SB), the piggyBac (PB) and Tol2, have been optimized for gene transfer into
      mammalian cells. In particular, SB resulted in stable gene transfer into various
      adult stem cells including human CD34(+) hematopoietic stem cells (HSCs),
      myoblasts and mesenchymal stem cells (MSCs). This has been confirmed with PB,
      yielding stable gene transfer in human CD34(+) HSCs. Recently, PB transposons
      were used to deliver the genes encoding the reprogramming factors into somatic
      cells making it an attractive technology for generating iPS cells. Subsequent de
      novo expression of the PB transposase resulted in traceless excision of the
      reprogramming cassette. This prevented inadvertent re-expression of the
      reprogramming factors obviating some of the concerns associated with the use of
      integrating vectors. Transposons have also been used as a novel non-viral
      paradigm to coax differentiation of iPS cells into their desired target cells by
      forced expression of specific differentiation factors. This review focuses on the
      emerging potential of transposons for gene transfer into stem cells and its
      implications for gene therapy and regenerative medicine.

PMID- 21864291
TI  - Patent review.

PMID- 21864292
TI  - Synergy of microRNA and stem cell: a novel therapeutic approach for diabetes
      mellitus and cardiovascular diseases.
AB  - MicroRNAs ( miRNAs) are highly conserved, 19-23 nucleotide long, non-coding,
      endogenous RNA, which are transcribed from either intergenic, intronic or
      polycistronic regions and modulate gene expression through mRNA degradation or
      translational repression. They are fine tuners of biological processes and have
      recently emerged as biomarkers and therapeutic targets of cardiovascular
      diseases. Several miRNAs regulate stem cell for differentiation, proliferation
      and degeneration. Stem cells are pluripotent, self-renewing and clonogenic cells
      having tremendous potential for regenerative therapy. The current therapeutic
      approach is unable to cope up with rapidly increasing rates of diabetes and
      cardiovascular diseases. The empirical and clinical evidences revealed that
      transplantation of exogenous stem cells can regenerate beta cells in diabetic
      patients and myocardium in patients with myocardial infarction. Nevertheless, the
      major limitation of stem cell therapy is unpredictable behavior of exogenous stem
      cells that incur few reports of teratoma and cancer after transplantation.
      Therefore, understanding the regulation of newly transplanted stem cells into the
      foreign body is a major challenge to translational research / clinical trail.
      Since miRNA plays pivotal role in the fine regulation of proliferation and
      differentiation of stem cells, investigations on the regulation of miRNA in
      transplanted stem cells in a specific micro-environment that houses the stem cell
      is indispensable. Additionally, the inhibition or over expression of specific
      miRNAs in the niche surrounding the stem cell will be crucial for maintaining the
      specific lineage of exogenous stem cells. This review embodies major advancement
      in the field of miRNA biogenesis and its regulatory mechanisms, role of different
      miRNAs and stem cells as a therapeutic target for diabetes and cardiovascular
      diseases. It also provides insights into the novel future therapy, where
      synergistic approach for manipulating miRNAs and stem cells will emerged as a
      potential treatment for diabetes and cardiovascular diseases.

PMID- 21864293
TI  - Common genetic aspects between polycystic ovary syndrome and diabetes mellitus.
AB  - Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disease that
      involves menstrual dysfunction and reproductive difficulty as well as metabolic
      problems. From a genetic point of view, it is a complex disease that is subject
      to environmental influences, mainly dietary, which makes it similar to other
      metabolic processes, such as diabetes and obesity. So, the interest of the
      diagnosis of the PCOS is, not only to improve fertility but to prevent possible
      future medical complications like the diabetes mellitus and the obesity. Due to
      the classical definition of PCOS as functional hyperandrogenism, the race to
      discover genetic alterations that could lead to the development of PCOS started
      with the androgen metabolism genes. However, the list of candidates was later
      expanded to other genes outside this hormonal pathway, and it now includes genes
      involved in carbohydrate and lipid metabolism as well as those involved in
      inflammatory processes. SYNOPSIS: The list of genes candidates involved in PCOS
      is related to diabetes and inflammatory processes.

PMID- 21864294
TI  - A novel class of PTEN protein in Arabidopsis displays unusual phosphoinositide
      phosphatase activity and efficiently binds phosphatidic acid.
AB  - PTEN (phosphatase and tensin homologue deleted on chromosome ten) proteins are
      dual phosphatases with both protein and phosphoinositide phosphatase activity.
      They modulate signalling pathways controlling growth, metabolism and apoptosis in
      animals and are implied in several human diseases. In the present paper we
      describe a novel class of PTEN pro-teins in plants, termed PTEN2, which comprises
      the AtPTEN (Arabidopsis PTEN) 2a and AtPTEN2b proteins in Arabidopsis. Both
      display low in vitro tyrosine phosphatase activity. In addition, AtPTEN2a
      actively dephosphorylates in vitro the 3' phosphate group of PI3P
      (phosphatidylinositol 3-phosphate), PI(3,4)P2 (phosphatidylinositol 3,4
      bisphosphate) and PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate). In contrast
      with animal PTENs, PI(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) is a
      poor substrate. Site-directed mutagenesis of AtPTEN2a and molecular modelling of
      protein-phosphoinositide interactions indicated that substitutions at the PTEN2
      core catalytic site of the Lys267 and Gly268 residues found in animals, which are
      critical for animal PTEN activity, by Met267 and Ala268 found in the eudicot
      PTEN2 are responsible for changes in substrate specificity. Remarkably, the
      AtPTEN2a protein also displays strong binding activity for PA (phosphatidic
      acid), a major lipid second messenger in plants. Promoter::GUS (beta
      glucuronidase) fusion, transcript and protein analyses further showed the
      transcriptional regulation of the ubiquitously expressed AtPTEN2a and AtPTEN2b by
      salt and osmotic stress. The results of the present study suggest a function for
      this novel class of plant PTEN proteins as an effector of lipid signalling in
      plants.

PMID- 21864295
TI  - Promoter hypermethylation of DNA damage response genes in hepatocellular
      carcinoma.
AB  - Aberrant methylation of promoter CpG islands is a major inactivation mechanism of
      tumour-related genes that play a crucial role in the progression of silencing in
      human cancers, including HCC (hepatocellular carcinoma). We have examined the
      promoter methylation status of five important DNA damage response genes in fresh
      frozen HCC tissues and cell lines, as well as the possible correlation between
      methylation patterns and clinical features of the carcinoma. Promoter methylation
      status of RASSF1A (Ras association domain family 1), CHFR (checkpoint with
      forkhead and ring finger domains), GSTP1 (glutathione-S-transferase-pi gene),
      MGMT [O(6)-methylguanine-DNA methyltransferase] and hMLH1 (human mutL homologue
      1) were examined by the MSP (methylation-specific PCR) in 70 HCC tissues and five
      HCC cell lines. The mRNA expression levels of these genes were measured by RT-PCR
      (reverse transcription-PCR). Methylation frequencies of these genes tested in HCC
      were 54 (78%) for RASSF1A, 30 (43%) for CHFR, 26 (38%) for GSTP1 and 22 (32%) for
      MGMT. No hypermethylation was detected for hMLH1 in any case of HCC or HCC cell
      lines. Moreover, promoter hypermethylation of RASSF1A, CHFR and GSTP1 in both
      HepG2 and SNU398 cells, and hypermethylation of MGMT in Huh7 cells, were
      detected. Treatment of three cell lines with 5Aza-dC (5-aza-20-deoxycytidine)
      restored or increased the expression of these genes, implicating aberrant DNA
      methylation in transcriptional silencing. Hypermethylation of RASSF1A and patient
      age were significantly associated. CHFR methylation status showed a statistically
      significant correlation with HCC progression. Methylation of the RASSF1A, CHFR,
      GSTP1 and MGMT genes seem therefore to play an important role in the pathogenesis
      of HCC. These epigenetic changes may have prognostic importance for patients with
      HCC.

PMID- 21864296
TI  - Absence of ABCG2-mediated mucosal detoxification in patients with active
      inflammatory bowel disease is due to impeded protein folding.
AB  - Xenotoxic damage in inflammatory diseases, including IBD (inflammatory bowel
      disease), is compounded by reduced activity of the xenobiotic transporter ABCG2
      (ATP-binding-cassette G2) during the inflammatory state. An association between
      the activation of the unfolded protein response pathway and inflammation prompted
      us to investigate the possibility that reduced ABCG2 activity is causally linked
      to this response. To this end, we correlated expression of ABCG2 and the unfolded
      protein response marker GRP78 (glucose-regulated protein of 78 kDa) in colon
      biopsies from healthy individuals (n=9) and patients with inactive (n=67) or
      active (n=55) IBD, ischaemic colitis (n=10) or infectious colitis (n=14). In
      addition, tissue specimens throughout the small bowel from healthy individuals
      (n=27) and from patients with inactive (n=9) or active (n=25) Crohn's disease
      were co-stained for ABCG2 and GRP78. In all biopsies from patients with active
      inflammation, irrespective of the underlying disease, an absolute negative
      correlation was observed between epithelial ABCG2 expression and GRP78
      expression, suggesting that inflammation-dependent activation of the unfolded
      protein response is responsible for suppression of ABCG2 function. The link
      between the unfolded protein response and functional ABCG2 expression was further
      corroborated by live imaging of ABCG2-expressing cells, which showed that various
      inflammatory mediators, including nitric oxide, activate the unfolded protein
      response and concomitantly reduce plasma membrane localization as well as
      transport function of ABCG2. Thus a novel mechanism for explaining xenobiotic
      stress during inflammation emerges in which intestinal inflammation activates the
      unfolded protein response, in turn abrogating defences against xenobiotic
      challenge by impairing ABCG2 expression and function.

PMID- 21864297
TI  - A common single nucleotide polymorphism A118G of the MU opioid receptor alters
      its N-glycosylation and protein stability.
AB  - The A118G SNP (single nucleotide polymorphism) of the hMOPR [human MOPR (MU
      opioid receptor)] gene OPRM1 results in an amino acid substitution (N40D).
      Subjects homozygous for the 118G allele have been reported to require higher
      morphine doses to achieve adequate analgesia, and the 118G allele is more
      prevalent among drug abusers. However, changes in the MOPR protein associated
      with this SNP are unknown. Using a knockin mouse model (G/G mice; mice homozygous
      for the 112G allele of MOPR) that possesses the equivalent nucleotide/amino acid
      substitution (A112G; N38D) of the A118G SNP in the hMOPR gene, we investigated
      the N-linked glycosylation status of thalamic and striatal MOPR in G/G mice
      compared with A/A mice (wild-type mice homozygous for the 112A allele of MOPR).
      The molecular mass of MOPR determined by immunoblotting was lower in G/G mice
      than in A/A mice. Following treatment with peptide N-glycosidase F, which removes
      all N-linked glycans, both MOPR variants had an identical molecular mass,
      indicating that this discrepancy was due to a lower level of N-glycosylation of
      the MOPR in G/G mice. In Chinese-hamster ovary cells stably expressing hMOPRs,
      118G/Asp40-hMOPR had a lower molecular mass than 118A/Asn40-hMOPR, which was
      similarly due to differential N-glycosylation. Pulse-chase studies revealed that
      the half-life of the mature form of 118G/Asp40-hMOPR (~12 h) was shorter than
      that of 118A/Asn40-hMOPR (~28 h). Thus the A118G SNP reduces MOPR N-glycosylation
      and protein stability.

PMID- 21864298
TI  - In vitro performance of a new non-invasive extracorporeal saturation monitor.
AB  - A simulated cardiopulmonary bypass circuit was constructed in the laboratory to
      compare the accuracy and precision of a new non-invasive extracorporeal oxygen
      saturation monitor-- the M3 monitor (Spectrum Medical LLP, Gloucester, UK)
      against the Siemens RAPIDLab((r)) blood gas analyser (Siemens AG, Munich,
      Germany). Comparisons were made across a range of oxygen saturations and at
      different temperatures and different haemoglobin concentrations. Results showed
      that under all conditions, when recording oxygen saturation, the M3 monitor
      achieved a mean (SD) bias of -0.9 (1.7)% with limits of clinical agreement of 
      4.2 to 2.5. However, the difference between the two monitors was larger at lower
      saturation levels (p < 0.001), lower haemoglobin levels (p = .002) and lower
      temperatures (p = 0.013). The mean (SD) haemoglobin concentration was 15.4 (0.6)
      when recorded by the M3 monitor, compared to 15.4 (0.5) g.dl(-1) measured by the
      blood gas analyser The M3 monitor compares favourably with the gold standard of
      the blood gas analyser and has the advantage of giving a continuous reading. You
      can respond to this article at http://www.anaesthesiacorrespondence.com.

PMID- 21864299
TI  - An analysis of scholarly productivity in United States academic
      anaesthesiologists by citation bibliometrics.
AB  - The h-index is used to evaluate scholarly productivity in academic medicine, but
      has not been extensively used in anaesthesia. We analysed the publications,
      citations, citations per publication and h-index from 1996 to date using the
      Scopus((r)) database for 1630 (1120 men, 510 women) for faculty members from 24
      randomly selected US academic anaesthesiology departments The median
      (interquartile range [range]) h-index of US academic anaesthesiologists was 1 [0
      5 (0-44)] with 3 [0-18 (0-398)] total publications, 24 [0-187 (0-8515)] total
      citations, and 5 [0-14 (0-252)] citations per publication. Faculty members in
      departments with National Institutes of Health funding were more productive than
      colleagues in departments with little or no government funding. The h-index
      increased significantly between successive academic ranks concomitant with
      increases in the number of publications and total citations. Men had higher
      median h-index than women concomitant with more publications and citations, but
      the number of citations per publication was similar between groups. Our results
      suggest that h-index is a reasonable indicator of scholarly productivity in
      anaesthesia. The results may help comparisons of academic productivity across
      countries and may be used to assess whether new initiatives designed to reverse
      recent declines in academic anaesthetic are working. You can respond to this
      article at http://www.anaesthesiacorrespondence.com.

PMID- 21864300
TI  - Sonographic assessment of arterial frequency and distribution within the brachial
      plexus: a comparison with the cadaveric record.
AB  - We investigated the number and distribution of arteries within the brachial
      plexus territory using a portable ultrasound device, and compared these findings
      with known cadaveric data. We recruited 200 volunteers and carried out 400
      brachial plexus examinations in a prospective observational study design. We
      identified arteries within the brachial plexus in more than 90% of subjects. Most
      of these were located in the upper and middle zones of the plexus and therefore
      lie within the possible path of a block needle. These findings correlate well
      with previous cadaveric studies, suggesting that arteries within the brachial
      plexus territory can be reliably identified with a portable ultrasound device.
      The presence of these vessels may impact upon the safety and efficacy of brachial
      plexus blockade. Routine pre-procedural sonographic assessment may offer improved
      safety and efficacy. You can respond to this article at
      http://www.anaesthesiacorrespondence.com.

PMID- 21864301
TI  - Measuring academic productivity: don't drop your 'h's!*.

PMID- 21864302
TI  - In this issue: September 2011.

PMID- 21864303
TI  - Age at first start and racing career of a cohort of Australian Standardbred
      horses.
AB  - OBJECTIVE Compare the career profiles of a cohort of Standardbred horses that
      first raced as 2-year-olds with those that started their racing careers at a
      later age. METHOD Retrospective analysis of the racing records of all foals born
      in New South Wales in the 2000 foaling season. RESULTS The career records of 999
      horses were analysed. Almost half (43.9%) first raced as 2-year-olds and one
      third (33.9%) as 3-year-olds. The median career duration for horses that first
      raced as 2-year-olds was 2.93 years (interquartile range (IQR) 2.70-3.16), which
      was significantly greater than the median for horses that first raced at 3, 4 or
      >=5 years old (P < 0.001). Males, and horses that first raced as 2-year-olds,
      earned significantly more prize money than females or horses that started racing
      aged >=3 years (P < 0.001). The population median number of career starts was
      28.0 (IQR 8-64). Males, and horses that first raced as 2-year-olds, had
      significantly more career starts than females or horses that started racing aged
      >=3 years (P < 0.001). CONCLUSION This study found no evidence suggesting that
      racing as a 2-year-old had a deleterious effect on a horse's racing career.

PMID- 21864304
TI  - Neurological diseases of ruminant livestock in Australia. IV: viral infections.
AB  - Most viral infections that affect the central nervous system of ruminants are
      exotic to Australia. As such, this review focuses on viruses of importance in
      Australian ruminants, including Akabane virus and the ruminant pestiviruses,
      bovine viral diarrhoea virus and border disease virus, as well as bluetongue
      virus. Each virus is discussed in terms of pathogenesis, clinical signs and
      diagnosis.

PMID- 21864305
TI  - Rumen fermentation and liveweight gain in beef cattle treated with monensin and
      grazing lush forage.
AB  - OBJECTIVE: To determine the prevalence of subacute rumen acidosis (SARA) in beef
      cattle grazing lush pasture and the effect of monensin on reducing SARA and
      improving animal performance. DESIGN: Commercial Angus and Murray Grey steers
      received a monensin slow-release capsule (n = 19) or remained untreated (n = 19).
      Cattle grazed an oats crop or tetraploid ryegrass pasture for a total of 91 days.
      Rumen fluid pH, volatile fatty acids (VFA) and lactic acid concentrations and
      body weight data were collected prior to treatment and again 28, 56 and 91 days
      after treatment. Changes in measures over time were analysed using mixed model
      repeated measures analysis. Differences in average daily gain between treatment
      groups were determined. RESULTS: The prevalence of SARA was low during the study,
      with only one animal satisfying criteria for SARA at one time point. Cattle
      treated with monensin capsules were 11.9 kg heavier at the completion of the
      study compared with untreated controls (414.5 +/- 3.88 kg vs 402.6 +/- 4.03 kg, P
      = 0.04). Rumen VFA and L- and D-lactate levels did not differ between cattle
      treated with monensin and untreated cattle. However, the ratio of propionate to
      acetate plus two times butyrate was higher (P < 0.001) when cattle were treated
      with monensin. CONCLUSIONS: Subacute rumen acidosis was not consistently detected
      under the conditions of the study. The higher body weight of cattle treated with
      monensin may have been due to improved energy utilisation of the pasture,
      indicated by increased propionate proportions in the rumen, rather than
      prevention of SARA.

PMID- 21864307
TI  - Treatment of refractory feline sporotrichosis with a combination of intralesional
      amphotericin B and oral itraconazole.
AB  - OBJECTIVE To describe the use of intralesional amphotericin B in localised
      lesions for the treatment of 26 cats from Rio de Janeiro, Brazil, with
      sporotrichosis refractory to oral itraconazole. DESIGN Uncontrolled intervention
      study. METHOD The 26 cats in this study were diagnosed with sporotrichosis,
      confirmed by isolation of Sporothrix schenckii, and presented residual localised
      skin lesions refractory to treatment with oral itraconazole for a minimum period
      of 8 weeks. The animals received weekly applications of intralesional
      amphotericin B in conjunction with oral itraconazole. In cases of owner
      unavailability, a maximum of 2 weeks between the infiltrations was accepted.
      RESULTS Twenty-two (84.6%) of the 26 treated cats achieved clinical remission, 16
      (72.7%) of which were cured, and in the remaining six (27.3%) the lesions
      recurred at the same site. Lack of clinical response was observed in one animal
      and three owners abandoned treatment. CONCLUSION The proposed therapeutic regimen
      is an adjunctive treatment option for cats with sporotrichosis presenting as
      residual skin lesions refractory to itraconazole.

PMID- 21864308
TI  - An analysis of the demand for and revenue from companion animal veterinary
      services in Australia between 1996 and 2026 using industry revenue data and
      household census and pet ownership data and forecasts.
AB  - OBJECTIVE To examine the potential impact of household demographic and pet
      ownership trends on the demand for and revenue from companion animal veterinary
      services in Australia. DESIGN The size of the market for companion animal
      veterinary services was estimated by creating a model using assumptions derived
      from the revenue equation. The model was verified and validated through
      sensitivity analyses and comparisons between model outputs and available industry
      data. RESULTS The model provided outputs similar to alternative industry
      estimates and suggested that revenue growth in recent years has been much
      stronger than demand growth. Under the assumptions used in this model, forecast
      changes to household numbers and types are less important than pet ownership
      trends in determining the potential demand for and revenue from companion animal
      veterinary services. Forecast trends in household types and relatively stable pet
      ownership in the future will lead to growth in demand for companion animal
      veterinary services in real terms of approximately 1.2% per annum to 2026.
      CONCLUSION The market for companion animal veterinary services in Australia is
      mature and growth in demand is expected to remain low over the forecast period.
      For most veterinary practices within this environment, growth in revenue will be
      a function of growth in average client fees.

PMID- 21864309
TI  - Influence of capture method, habitat quality and individual traits on blood
      parameters of free-ranging lace monitors (Varanus varius).
AB  - OBJECTIVE The aims of this study were to determine baseline reference intervals
      for haematological and serum biochemical parameters in lace monitors, and to
      examine whether such values were influenced by capture method, expected
      differences in habitat food resource availability and a lizard's body size and
      body condition. METHODS Thirty-three wild Victorian lace monitors (Varanus
      varius) of unknown age and sex were captured by noose pole or aluminium box trap
      from Cape Conran in East Gippsland, Victoria, Australia. RESULTS No statistical
      differences between the two capture methods were noted for haematology. There was
      a significant difference in the serum glucose concentrations between the two
      methods of capture (higher concentration in box-trapped animals) because of a
      physiological response to capture stress. Habitat food quality did not appear to
      influence haematology or serum biochemistry. The packed cell volume (PCV) for the
      lace monitors was 0.29-0.43 L/L. Lymphocytes were identified as the most common
      leucocyte. The haemoprotozoan parasite, Haemogregarina varanicola, was found in
      all 33 blood samples. No correlation could be made between parasite burden and
      PCV, serum globulins or serum proteins, but animals in poor body condition were
      more likely to harbour large numbers of parasites. CONCLUSION The results of this
      study may be used as a basis for evaluating health in lace monitors.

PMID- 21864310
TI  - Quarantine, exports and animal disease in Australia 1901-2010.
AB  - The Constitution forming the Australian Commonwealth Government on 1 January 1901
      provided that animal and animal products imported into and exported from
      Australia would be under the authority of the national government. By mutual
      agreement, the Quarantine Act 1908 provided for the states to continue the
      delivery of services under contract until 1995 when the Commonwealth took back
      full responsibility for quarantine services. In the 1940s, 50s and 60s there were
      world pandemics of livestock diseases and Australia ceased the import of many
      species. By the 1970s, the livestock industries sought relaxation of import
      restrictions to gain access to diversified genetic stock. By the use of new
      technologies, many species can now be imported into Australia through tight
      importation protocols. With the advent of the World Trade Organization and
      implementation of the Sanitary Phytosanitary Agreement, Australia has developed a
      risk-based framework to support the development of import conditions for animals
      and animal products. Australia's 'Acceptable Level of Protection' has been set to
      provide a low likelihood of disease entry. Being an island continent, Australia
      can apply strong controls over imports and exports of all commodities and
      relatively few outbreaks of exotic animal diseases have occurred by breach of
      quarantine, but the outbreaks of rinderpest in 1923 and equine influenza in 2007
      were notable exceptions.

PMID- 21864311
TI  - Lifting the lid on GPCRs: the role of extracellular loops.
AB  - GPCRs exhibit a common architecture of seven transmembrane helices (TMs) linked
      by intracellular loops and extracellular loops (ECLs). Given their peripheral
      location to the site of G-protein interaction, it might be assumed that ECL
      segments merely link the important TMs within the helical bundle of the receptor.
      However, compelling evidence has emerged in recent years revealing a critical
      role for ECLs in many fundamental aspects of GPCR function, which supported by
      recent GPCR crystal structures has provided mechanistic insights. This review
      will present current understanding of the key roles of ECLs in ligand binding,
      activation and regulation of both family A and family B GPCRs.

PMID- 21864312
TI  - Endothelin and bradykinin: 'brothers-in-arms' in Chagas vasculopathies?
AB  - Reports of Chagas disease are increasing in non-endemic populations across the
      globe. Apart from vector eradication and prevention efforts by public health
      organizations, current pharmacological interventions are sparse and show
      important side effects. In this issue of the BJP, Andrade et al. elegantly
      demonstrate a new pharmacological paradigm whereby Trypanosoma cruzi host cell
      invasion requires significant cross-talk between receptors for kinins and
      endothelins. It is shown, for example, that acting via both ET(A) and ET(B)
      receptors, endothelin-1 (ET-1) cooperates with the (TLR2/CXCR2/B(2) kinin
      receptor) complex to activate inflammatory processes in response to invading
      trypomastigotes. This study by Andrade et al. prompts, however, several important
      questions, summarized in this Commentary, such as the putative role of chymase
      dependent production of ET-1, the contentious protective role of ACE inhibitors
      in Chagasic patients, the unexplored role of de novo formed B(1) receptors for
      kinins triggered by cytokines and the putative role of compartmentalized calcium
      pools in host cell invasion by trypomastigotes.

PMID- 21864313
TI  - A naturally occurring naringenin derivative exerts potent bone anabolic effects
      by mimicking oestrogen action on osteoblasts.
AB  - BACKGROUND AND PURPOSE: Naringenin and its derivatives have been assessed in bone
      health for their oestrogen-'like' effects but low bioavailability impedes
      clinical potential. This study was aimed at finding a potent form of naringenin
      with osteogenic action. EXPERIMENTAL APPROACH: Osteoblast cultures were harvested
      from mouse calvaria to study differentiation by naringenin, isosakuranetin,
      poncirin, phloretin and naringenin-6-C-glucoside (NCG). Balb/cByJ ovariectomized
      (OVx) mice without or with osteopenia were given naringenin, NCG, 17beta
      oestradiol (E2) or parathyroid hormone (PTH). Efficacy was evaluated by bone
      microarchitecture using microcomputed tomography and determination of new bone
      formation by fluorescent labelling of bone. Plasma levels of NCG and naringenin
      were determined by HPLC. KEY RESULTS: NCG stimulated osteoblast differentiation
      more potently than naringenin, while isosakuranetin, poncirin or phloretin had no
      effect. NCG had better oral bioavailability than naringenin. NCG increased the
      mRNA levels of oestrogen receptors (ERs) and bone morphogenetic protein (an ER
      responsive gene) in vivo, more than naringenin. In OVx mice, NCG treatment in a
      preventive protocol increased bone formation rate (BFR) and improved trabecular
      microarchitecture more than naringenin or E2. In osteopenic mice, NCG but not
      naringenin, in a therapeutic protocol, increased BFR and improved trabecular
      microarchitecture, comparable with effects of PTH treatment. Stimulatory effects
      of NCG on osteoblasts were abolished by an ER antagonist. NCG transactivated
      ERbeta but not ERalpha. NCG exhibited no uterine oestrogenicity unlike
      naringenin. CONCLUSIONS AND IMPLICATIONS: NCG is a potent derivative of
      naringenin that has bone anabolic action through the activation of osteoblast ERs
      and exhibited substantial oral bioavailability.

PMID- 21864315
TI  - Recognition of scared faces and the serotonin transporter gene in young children:
      the Generation R Study.
AB  - BACKGROUND: Previous research highlights the significance of a functional
      polymorphism located in the promoter region (5-HTTLPR) of the serotonin
      transporter gene in emotional behaviour. This study examined the effect of the 5
      HTTLPR polymorphism on emotion processing in a large number of healthy
      preschoolers. METHODS: The 5-HTTLPR genotype was classified in 605 children as
      homozygous for the short allele (SS), homozygous for the long allele (LL), or
      heterozygous (LS). Emotion-processing was assessed using age-appropriate computer
      tasks where children matched happy, sad, angry, and fearful facial expressions
      preceded by a shape-matching task to assess basic matching ability. RESULTS: We
      found that young children could differentiate between emotion categories (F =
      12.1, p < .001). The effect of 5-HTTLPR genotype depended on the emotion category
      presented (F = 2.3, p = .031). This effect was explained by the finding that SS
      children were less accurate at recognising fearful faces than LL or LS children
      (F = 5.3, p = .005). We did not find any significant differences as a result of 5
      HTTLPR genotype for happy, sad or angry expressions (p > .05). CONCLUSIONS:
      Results indicate that 5-HTTLPR allele status selectively impacts the processing
      of fearful but not other facial expressions. This pattern is already apparent in
      very young typically developing children. Results may signal an early
      vulnerability for affective problems before disorders emerge.

PMID- 21864316
TI  - Pathology of oesophagitis.
AB  - Endoscopic oesophageal biopsies are common in daily pathology practice.
      Inflammation and damage of the oesophageal mucosa is known as oesophagitis and is
      common worldwide. A variety of physical, chemical and infectious agents cause
      oesophagitis. The oesophagus has a limited range of responses to a wide variety
      of injuries, and so histopathological features of different diseases often
      overlap. The pathologist is reliant on the endoscopist for the 'macroscopic
      description' of the oesophagus. Access to the endoscopic images enhances the
      pathologist's overall interpretation of the case. Correlating clinical,
      endoscopic and microscopic findings may be crucial in arriving at the correct
      diagnosis. In this review, we present clinicopathological descriptions of the
      major types of oesophagitis.

PMID- 21864314
TI  - Enhancing the utility of existing antibiotics by targeting bacterial behaviour?
AB  - The discovery of novel classes of antibiotics has slowed dramatically. This has
      occurred during a time when the appearance of resistant strains of bacteria has
      shown a substantial increase. Concern is therefore mounting over our ability to
      continue to treat infections in an effective manner using the antibiotics that
      are currently available. While ongoing efforts to discover new antibiotics are
      important, these must be coupled with strategies that aim to maintain as far as
      possible the spectrum of activity of existing antibiotics. In many instances, the
      resistance to antibiotics exhibited by bacteria in chronic infections is mediated
      not by direct resistance mechanisms, but by the adoption of modes of growth that
      confer reduced susceptibility. These include the formation of biofilms and the
      occurrence of subpopulations of 'persister' cells. As our understanding of these
      processes has increased, a number of new potential drug targets have been
      revealed. Here, advances in our ability to disrupt these systems that confer
      reduced susceptibility, and in turn increase the efficacy of antibiotic therapy,
      are discussed.

PMID- 21864317
TI  - Patterns of p53 immunoreactivity in endometrial carcinomas: 'all or nothing'
      staining is of importance.

PMID- 21864318
TI  - Impairing somatosensory working memory using rTMS.
AB  - Numerous studies in animals and humans have related central aspects of
      somatosensory working memory function to neural activity in the inferior frontal
      gyrus (IFG). However, as previous studies have almost exclusively used
      correlational analyses, the question whether sustained neural activity in the IFG
      is causally involved in successful maintenance of somatosensory information
      remains unanswered. We used an online repetitive transcranial magnetic
      stimulation (rTMS) protocol to disrupt neuronal activity in the IFG while
      participants were maintaining tactile information throughout the delay for later
      comparison against a probe stimulus. rTMS impaired participants' performance in
      the working memory task, but not in a physically matched perceptual control task.
      Targeting the IFG in either hemisphere led to comparable working memory
      impairment. Our results show that the neural activity in the IFG plays a causal
      role in successful maintenance of somatosensory information.

PMID- 21864319
TI  - Visual adaptation and novelty responses in the superior colliculus.
AB  - The brain's ability to ignore repeating, often redundant, information while
      enhancing novel information processing is paramount to survival. When stimuli are
      repeatedly presented, the response of visually sensitive neurons decreases in
      magnitude, that is, neurons adapt or habituate, although the mechanism is not yet
      known. We monitored the activity of visual neurons in the superior colliculus
      (SC) of rhesus monkeys who actively fixated while repeated visual events were
      presented. We dissociated adaptation from habituation as mechanisms of the
      response decrement by using a Bayesian model of adaptation, and by employing a
      paradigm including rare trials that included an oddball stimulus that was either
      brighter or dimmer. If the mechanism is adaptation, response recovery should be
      seen only for the brighter stimulus; if the mechanism is habituation, response
      recovery ('dishabituation') should be seen for both the brighter and dimmer
      stimuli. We observed a reduction in the magnitude of the initial transient
      response and an increase in response onset latency with stimulus repetition for
      all visually responsive neurons in the SC. Response decrement was successfully
      captured by the adaptation model, which also predicted the effects of
      presentation rate and rare luminance changes. However, in a subset of neurons
      with sustained activity in response to visual stimuli, a novelty signal akin to
      dishabituation was observed late in the visual response profile for both brighter
      and dimmer stimuli, and was not captured by the model. This suggests that SC
      neurons integrate both rapidly discounted information about repeating stimuli and
      novelty information about oddball events, to support efficient selection in a
      cluttered dynamic world.

PMID- 21864320
TI  - Developmental underpinnings of differences in rodent novelty-seeking and
      emotional reactivity.
AB  - Innate differences in human temperament strongly influence how individuals cope
      with stress and also predispose towards specific types of psychopathology. The
      present study examines the developing brain in an animal model of temperamental
      differences to examine how altered neurodevelopment may engender differences in
      emotional reactivity that are stable throughout the animal's life. We utilize
      selectively-bred High Responder (bHR) and Low Responder (bLR) rats that exhibit
      dramatic emotional behavior differences, with bHRs exhibiting exaggerated novelty
      exploration, aggression, impulsivity and drug self-administration, and bLRs
      showing marked behavioral inhibition and exaggerated anxiety-like and depressive
      like behavior. Using Affymetrix microarrays, we assessed bLR and bHR gene
      expression in the developing brain on postnatal days (P)7, 14 and 21, focusing on
      the hippocampus and nucleus accumbens, two regions related to emotionality and
      known to differ in adult bLR and bHR rats. We found dramatic gene expression
      differences between bLR and bHR in the P7 and P14 hippocampus, with minimal
      differences in the nucleus accumbens. Some of the most profound differences
      involved genes critical for neurodevelopment and synaptogenesis. Stereological
      studies evaluated hippocampal structure in developing bHR and bLR pups, revealing
      enhanced hippocampal volume and cell proliferation in bLR animals. Finally,
      behavioral studies showed that the characteristic bHR and bLR behavioral
      phenotypes emerge very early in life, with exploratory differences apparent at
      P16 and anxiety differences present by P25. Together these data point to specific
      brain regions and critical periods when the bHR and bLR phenotypes begin to
      diverge, which may eventually allow us to test possible therapeutic interventions
      to normalize extreme phenotypes (e.g. the anxiety-prone nature of bLRs or drug
      addiction proclivity of bHRs).

PMID- 21864321
TI  - Nav 1.1 dysfunction in genetic epilepsy with febrile seizures-plus or Dravet
      syndrome.
AB  - Relatively few SCN1A mutations associated with genetic epilepsy with febrile
      seizures-plus (GEFS+) and Dravet syndrome (DS) have been functionally
      characterized. In contrast to GEFS+, many mutations detected in DS patients are
      predicted to have complete loss of function. However, functional consequences are
      not immediately apparent for DS missense mutations. Therefore, we performed a
      biophysical analysis of three SCN1A missense mutations (R865G, R946C and R946H)
      we detected in six patients with DS. Furthermore, we compared the functionality
      of the R865G DS mutation with that of a R859H mutation detected in a GEFS+
      patient; the two mutations reside in the same voltage sensor domain of Na(v) 1.1.
      The four mutations were co-expressed with beta1 and beta2 subunits in tsA201
      cells, and characterized using the whole-cell patch clamp technique. The two DS
      mutations, R946C and R946H, were nonfunctional. However, the novel voltage sensor
      mutants R859H (GEFS+) and R865G (DS) produced sodium current densities similar to
      those in wild-type channels. Both mutants had negative shifts in the voltage
      dependence of activation, slower recovery from inactivation, and increased
      persistent current. Only the GEFS+ mutant exhibited a loss of function in voltage
      dependent channel availability. Our results suggest that the R859H mutation
      causes GEFS+ by a mixture of biophysical defects in Na(v) 1.1 gating.
      Interestingly, while loss of Na(v) 1.1 function is common in DS, the R865G
      mutation may cause DS by overall gain-of-function defects.

PMID- 21864322
TI  - Wheel running can accelerate or delay extinction of conditioned place preference
      for cocaine in male C57BL/6J mice, depending on timing of wheel access.
AB  - Aerobic exercise may represent a useful intervention for drug abuse in
      predisposed individuals. Exercise increases plasticity in the brain that could be
      used to reverse learned drug associations. Previous studies have reported that
      exposing mice to a complex environment including running wheels after drug
      conditioning abolishes conditioned place preference (CPP) for cocaine, whereas
      running can enhance CPP when administered before conditioning. The purpose of the
      present study was to test the hypothesis that timing of exercise relative to
      conditioning has opposing effects on cocaine CPP. Male C57BL/6J mice experienced
      30 days of running or sedentary treatments either before or after cocaine
      conditioning. Control animals always received saline and never cocaine, but
      otherwise underwent the same conditioning and exercise treatments. Animals were
      given bromodeoxyuridine injections at the onset of conditioning or exercise, and
      euthanized at the end of the study to quantify survival of new neurons in the
      hippocampus as a marker of plasticity. Wheel running accelerated extinction of
      CPP when running occurred entirely after drug conditioning, whereas running
      delayed extinction when administered before conditioning. A single conditioning
      day after running was sufficient to abolish the accelerated extinction observed
      when all conditioning preceded running. Running approximately doubled adult
      hippocampal neurogenesis, whereas cocaine had no effect. These results suggest
      that exercise-induced plasticity can facilitate learning that context is no
      longer associated with drug. However, if drug exposure occurs after exercise,
      running-induced plasticity may strengthen drug associations. The results provide
      insights into the interaction between exercise and drug conditioning that could
      have implications for drug abuse treatments.

PMID- 21864323
TI  - 50,000 years of genetic uniformity in the critically endangered Iberian lynx.
AB  - Low genetic diversity in the endangered Iberian lynx, including lack of
      mitochondrial control region variation, is thought to result from historical or
      Pleistocene/Holocene population bottlenecks, and to indicate poor long-term
      viability. We find no variability in control region sequences from 19 Iberian
      lynx remains from across the Iberian Peninsula and spanning the last 50,000
      years. This is best explained by continuously small female effective population
      size through time. We conclude that low genetic variability in the Iberian lynx
      is not in itself a threat to long-term viability, and so should not preclude
      conservation efforts.

PMID- 21864324
TI  - A long-term prospective study to compare the effects of vaginal and abdominal
      hysterectomy on micturition and defecation.
AB  - OBJECTIVE: We compared micturition and defecation symptoms with the route of
      hysterectomy over a period of 10 years. DESIGN: Prospective multicentre
      observational study. SETTING: Thirteen teaching hospitals in the Netherlands.
      POPULATION: A total of 430 women who underwent vaginal or abdominal hysterectomy
      for benign conditions (pelvic organ prolapse excluded). METHODS: The presence and
      discomfort experienced as a result of micturition and defecation symptoms were
      assessed using validated questionnaires before surgery, and at 6 weeks, 6 months,
      1 year, 3 years and 10 years after surgery. Statistically significant differences
      in symptoms between vaginal and abdominal hysterectomy were adjusted for pre
      operative differences in uterine descent, uterine size, parity and indication for
      hysterectomy. MAIN OUTCOME MEASURE: Presence of bothersome micturition and
      defecation symptoms, as assessed by the Urogenital Distress Inventory (UDI) and
      Defecation Distress Inventory (DDI). RESULTS: Ten years after hysterectomy the
      response rate was 73%. Preoperatively, no differences were observed in the
      prevalence of micturition symptoms between patients who underwent vaginal and
      abdominal hysterectomy. However, 10 years after vaginal hysterectomy,
      significantly more women had been treated for micturition symptoms (18 versus 8%;
      P = 0.02; adjusted OR 3.8, 95% CI 1.2-11.6). Defecation symptoms also seemed more
      common after vaginal hysterectomy (58 versus 46%; P = 0.08). After adjustment, no
      statistically significant differences in defecation symptoms were found.
      CONCLUSIONS: Despite the same incidence of micturition symptoms before surgery,
      patients undergoing vaginal hysterectomy are more likely to seek medical help for
      micturition symptoms. Defecation symptoms were also more common after vaginal
      hysterectomy; however, this difference was not statistically significant.

PMID- 21864325
TI  - Primary surgical repair of anterior vaginal prolapse: a randomised trial
      comparing anatomical and functional outcome between anterior colporrhaphy and
      trocar-guided transobturator anterior mesh.
AB  - OBJECTIVE: To compare anterior colporrhaphy with a trocar-guided transobturator
      mesh procedure (Avaulta((r)) anterior). DESIGN: Randomised, controlled trial.
      SETTING: Three teaching hospitals. POPULATION: Women with a symptomatic cystocele
      at least stage II requiring primary surgical correction. METHODS: A total of 125
      women were assessed at baseline and 1-year follow up. A sacrospinous hysteropexy
      or posterior colporrhaphy was performed when indicated. MAIN OUTCOME MEASURES:
      The primary outcome was the difference in anatomical cure (defined as Pelvic
      Organ Prolapse-Quantification <stage II cystocele). Secondary outcomes were
      complications, self-reported urogenital symptom severity, and quality of life, as
      measured with validated questionnaires. RESULTS: In all, 64 women were allocated
      to the anterior colporrhaphy group and 61 to the mesh group; 58/64 women versus
      56/61 completed 12 months of follow-up analysis. Compared with the anterior
      colporrhaphy group, the mesh reduced the risk of anatomical failure at 12 months
      follow up from 59 to 9% (risk reduction 50.3%, 95% CI 35.5-65.1). Only three (5%)
      re-operations for anatomical failure in the anterior colporrhaphy group were
      performed versus 0% in the mesh group. Functional outcome improved significantly
      at 12 months on almost all domains, with similar results between groups. Mesh
      exposure occurred in two (4%) women. Baseline dyspareunia disappeared
      significantly more often after an anterior colporrhaphy (80%) than in the mesh
      group (20%). There was a trend towards more de novo dyspareunia in the mesh group
      (15% versus 9%). CONCLUSIONS: Primary cystocele repair with trocar-guided
      transobturator mesh resulted in a statistically significant better anatomical
      outcome compared with the anterior colporrhaphy. However, functional outcome was
      similar between groups.

PMID- 21864326
TI  - Missed opportunities for type 2 diabetes testing following gestational diabetes:
      a population-based cohort study.
AB  - OBJECTIVES: Few women with gestational diabetes (GDM) are tested for type 2
      diabetes in the postpartum period. Whether women are having physician visits that
      could be an opportunity to improve testing rates is unknown. This study sought to
      evaluate population-level trends in postpartum diabetes testing after GDM, and to
      evaluate postpartum physician care for these women. DESIGN: Population-based
      cohort study. SETTING: Ontario, Canada. POPULATION: Women who delivered between
      1994 and 2008. METHODS: Using population-level healthcare databases, we
      identified 47,691 women with GDM. They were matched to women without GDM. MAIN
      OUTCOME MEASURES: An oral glucose tolerance test (OGTT) within 6 months
      postpartum, the specialty of the physician ordering the test, and ambulatory care
      visits with physicians from various specialties within 6 months postpartum were
      recorded. RESULTS: Most women with GDM did not receive an OGTT, although testing
      rates increased slowly over the 14 years of the study, compared with no change in
      testing for women who had not had GDM. Virtually all women with GDM had
      postpartum visits with a family physician or obstetrician, but few OGTTs were
      ordered by physicians from these specialties. CONCLUSIONS: Despite a slow
      increase in testing over time and high rates of postpartum visits to family
      physicians and obstetricians, few women with GDM received the recommended
      diabetes test. This represents a missed opportunity in a high-risk population.
      Interventions to change test ordering that target family physicians and
      obstetricians are most likely to increase the proportion of women with GDM who
      receive postpartum diabetes testing.

PMID- 21864327
TI  - Toxoplasma gondii infection in humans in China.
AB  - Toxoplasmosis is a zoonotic infection of humans and animals, caused by the
      opportunistic protozoan Toxoplasma gondii, a parasite belonging to the phylum
      Apicomplexa. Infection in pregnant women may lead to abortion, stillbirth or
      other serious consequences in newborns. Infection in immunocompromised patients
      can be fatal if not treated. On average, one third of people are chronically
      infected worldwide. Although very limited information from China has been
      published in the English journals, T. gondii infection is actually a significant
      human health problem in China. In the present article, we reviewed the clinical
      features, transmission, prevalence of T. gondii infection in humans in China, and
      summarized genetic characterizations of reported T. gondii isolates. Educating
      the public about the risks associated with unhealthy food and life style habits,
      tracking serological examinations to special populations, and measures to
      strengthen food and occupational safety are discussed.

PMID- 21864329
TI  - Unusual exanthema combined with cerebral vasculitis in pneumococcal meningitis: a
      case report.
AB  - INTRODUCTION: Bacterial meningitis is a complex, rapidly progressive disease in
      which neurological injury is caused in part by the causative organism and in part
      by the host's own inflammatory responses. CASE PRESENTATION: We present the case
      of a two-year-old Greek girl with pneumococcal meningitis and an atypical
      curvilinear-like skin eruption, chronologically associated with cerebral
      vasculitis. A diffusion-weighted MRI scan showed lesions with restricted
      diffusion, reflecting local areas of immunologically mediated necrotizing
      vasculitis. CONCLUSIONS: Atypical presentations of bacterial meningitis may
      occur, and they can be accompanied by serious unexpected complications.

PMID- 21864328
TI  - Improved blastocyst development of single cow OPU-derived presumptive zygotes by
      group culture with agarose-embedded helper embryos.
AB  - BACKGROUND: The in vitro culture of presumed zygotes derived from single cow ovum
      pick-up (OPU) is important for the production of quality blastocysts maintaining
      pedigree. The aim of the present study was to evaluate the agar chip-embedded
      helper embryo coculture system for single cow OPU-derived zygotes by assessing
      embryo quality. METHODS: Cumulus oocyte complexes (COCs) were collected from
      Hanwoo cows with high genetic merit twice a week using the ultra-sound guided OPU
      technique and from slaughterhouse ovaries. The Hanwoo cow COCs and slaughterhouse
      ovaries were matured in vitro, fertilized in vitro with thawed Hanwoo sperm and
      cultured for 24 h. The presumed zygotes were subsequently placed in three
      different culture systems: (1) control OPU (controlOPU) with single cow OPU
      derived presumed zygotes (2~8); (2) agar chip-embedded slaughterhouse helper
      embryo coculture (agarOPU) with ten presumed zygotes including all presumed
      zygotes from a cow (2~8) and the rest from agar chip-embedded slaughterhouse
      presumed zygotes (8~2); and (3) slaughterhouse in vitro embryo production (sIVP)
      with ten slaughterhouse ovary-derived presumed zygotes, each in 50 MUL droplets.
      Day 8 blastocysts were assayed for apoptosis and gene expression using real time
      PCR. RESULTS: The coculture system promoted higher blastocyst development in OPU
      zygotes compared to control OPU zygotes cultured alone (35.2 vs. 13.9%; P <
      0.01). Genes predicted to be involved in implantation failure and/or embryo
      resorption were down-regulated (P < 0.05) in control OPU zygotes (CD9, 0.4-fold;
      AKRAB1, 0.3-fold) and in cocultured zygotes (CD9, 0.3-fold; AKRAB1, 0.3-fold)
      compared to sIVP blastocysts (1.0-fold). Moreover, genes involved in implantation
      and/or normal calf delivery were up-regulated (P < 0.05 to P < 0.01) in control
      OPU zygotes (PGSH2, 5.0-fold; TXN, 4.3-fold; PLAU, 1.7-fold) and cocultured
      zygotes (PGSH2, 14.5-fold; TXN, 3.2-fold; PLAU, 6.8-fold) compared to sIVP (1.0
      fold) blastocysts. However, the expression of PLAC8, TGF-beta1, ODC1, ATP5A1 and
      CASP3 did not differ between the three culture groups. CONCLUSIONS: Results show
      that the agar chip-embedded helper embryo coculture system enhances developmental
      competence and embryo quality in cultures of limited numbers of high pedigree
      single cow OPU presumed zygotes.

PMID- 21864330
TI  - Do expert assessments converge? An exploratory case study of evaluating and
      managing a blood supply risk.
AB  - BACKGROUND: Examining professional assessments of a blood product
      recall/withdrawal and its implications for risk and public health, the paper
      introduces ideas about perceptions of minimal risk and its management. It also
      describes the context of publicly funded blood transfusion in Canada and the
      withdrawal event that is the basis of this study. METHODS: Interviews with 45
      experts from administration, medicine, blood supply, laboratory services and risk
      assessment took place using a multi-level sampling framework in the aftermath of
      the recall. These experts either directly dealt with the withdrawal or were
      involved in the management of the blood supply at the national level. Data from
      these interviews were coded in NVivo for analysis and interpretation.
      Analytically, data were interpreted to derive typifications to relate interview
      responses to risk management heuristics. RESULTS: While all those interviewed
      agreed on the importance of patient safety, differences in the ways in which the
      risk was contextualized and explicated were discerned. Risk was seen in terms of
      patient safety, liability or precaution. These different risk logics are
      illustrated by selected quotations. CONCLUSIONS: Expert assessments did not fully
      converge and it is possible that these different risk logics and discourses may
      affect the risk management process more generally, although not necessarily in a
      negative way. Patient safety is not to be compromised but management of blood
      risk in publicly funded systems may vary. We suggest ways of managing blood risk
      using formal and safety case approaches.

PMID- 21864331
TI  - Synthesis and characterization of aligned ZnO/BeO core/shell nanocable arrays on
      glass substrate.
AB  - By sequential hydrothermal growth of ZnO nanowire arrays and thermal evaporation
      of Be, large-scale vertically aligned ZnO/BeO core/shell nanocable arrays on
      glass substrate have been successfully synthesized without further heat
      treatment. Detailed characterizations on the sample morphologies, compositions,
      and microstructures were systematically carried out, which results disclose the
      growth behaviors of the ZnO/BeO nanocable. Furthermore, incorporation of BeO
      shell onto ZnO core resulted in distinct improvement of optical properties of ZnO
      nanowire, i.e., significant enhancement of near band edge (NBE) emission as well
      as effective suppression of defects emission in ZnO. In particular, the NBE
      emission of nanocable sample shows a noticeable blue-shift compared with that of
      pristine ZnO nanowire, which characteristics most likely originate from Be
      alloying into ZnO. Consequently, the integration of ZnO and BeO into nanoscale
      heterostructure could bring up new opportunities in developing ZnO-based device
      for application in deep ultraviolet region. PACS: 61.46.K; 78.67.Uh; 81.07.Gf.

PMID- 21864332
TI  - Delayed onset of tricuspid valve flow in repaired tetralogy of Fallot: an
      additional mechanism of diastolic dysfunction and interventricular dyssynchrony.
AB  - BACKGROUND: Diastolic dysfunction of the right ventricle (RV) is common after
      repair of tetralogy of Fallot. While restrictive physiology in late diastole has
      been well known, dysfunction in early diastole has not been described. The
      present study sought to assess the prevalence and mechanism of early diastolic
      dysfunction of the RV defined as delayed onset of the tricuspid valve (TV) flow
      after TOF repair. METHODS: The study population consisted of 31 children with
      repaired TOF (mean age +/- SD, 12.3 +/- 4.1 years) who underwent postoperative
      cardiovascular magnetic resonance (CMR). The CMR protocol included simultaneous
      phase-contrast velocity mapping of the atrioventricular valves, which enabled
      direct comparison of the timing and patterns of tricuspid (TV) and mitral (MV)
      valve flow. The TV flow was defined to have delayed onset when its onset was > 20
      ms later than the onset of the MV flow. The TV and MV flow from 14 normal
      children was used for comparison. The CMR results were correlated with the
      findings on echocardiography and electrocardiography. RESULT: Delayed onset of
      the TV flow was observed in 16/31 patients and in none of the controls. The mean
      delay time was 64.81 +/- 27.07 ms (8.7 +/- 3.2% of R-R interval). The delay time
      correlated with the differences in duration of the TV and MV flow (55.94 +/-
      32.88 ms) (r = 0.90, p < 0.001). Delayed onset was associated with prolongation
      of the RV ejection time in 9 and delayed onset and cessation of the pulmonary
      arterial flow in 4. Delayed onset was not associated with timing changes in the
      pulmonary artery in 3. The patients with delayed onset showed reduced RV ejection
      fraction (p = 0.01). However, the two groups did not show significant differences
      in TV E/A ratio, ventricular end-diastolic volumes, left ventricular ejection
      fraction, pulmonary regurgitant fraction, heart rate, PR interval and QRS
      duration. CONCLUSIONS: Early diastolic dysfunction with delayed onset of TV flow
      is common after TOF repair, and is associated with reduced RV ejection fraction.
      It is a further manifestation of interventricular dyssynchrony and represent an
      additional mechanism of ventricular diastolic dysfunction.

PMID- 21864333
TI  - Neurogenin2 regulates the initial axon guidance of cortical pyramidal neurons
      projecting medially to the corpus callosum.
AB  - BACKGROUND: The formation of the mammalian central nervous system requires the
      establishment of complex neural circuits between a diverse array of neuronal
      subtypes. Here we report that the proneural transcription factor Neurogenin2
      (Ngn2) is crucial for the proper specification of cortical axon projections.
      RESULTS: The genetic loss of Ngn2 in mice results in fewer callosal axons
      projecting towards the midline as well as abnormal midline crossing. shRNA
      mediated knockdown of Ngn2 revealed its cell-autonomous requirement for the
      proper projection of axons from layer 2/3 pyramidal neurons to the midline in
      vivo. We found that the acute loss of Ngn2 in vivo induces the axon of
      superficial layer 2/3 neurons to project laterally towards aberrant cortical and
      subcortical targets. CONCLUSIONS: These and previous results demonstrate that
      Ngn2 is required for the coordinated specification of cardinal features defining
      the phenotype of cortical pyramidal neurons, including their migration
      properties, dendritic morphology and axonal projection.

PMID- 21864334
TI  - Coordinated increase in inhibitory and excitatory synapses onto retinal ganglion
      cells during development.
AB  - BACKGROUND: Neuronal output is shaped by a balance of excitation and inhibition.
      How this balance is attained in the central nervous system during development is
      not well understood, and is complicated by the fact that, in vivo, GABAergic and
      glycinergic synaptogenesis precedes that of glutamatergic synapses. Here, we
      determined the distributions of inhibitory postsynaptic sites on the dendritic
      arbors of individual neurons, and compared their developmental patterns with that
      of excitatory postsynaptic sites. We focused on retinal ganglion cells (RGCs),
      the output neurons of the retina, which receive excitatory input from bipolar
      cells and inhibitory input from amacrine cells. To visualize and map inhibitory
      postsynaptic sites, we generated transgenic mice in which RGCs express
      fluorescently tagged Neuroligin 2 (YFP-NL2) under the control of the Thy1
      promoter. By labeling RGC dendrites biolistically in YFP-NL2-expressing retinas,
      we were able to map the spatial distribution and thus densities of inhibitory
      postsynaptic sites on the dendritic arbors of individual large-field RGCs across
      ages. RESULTS: We demonstrate that YFP-NL2 is present at inhibitory synapses in
      the inner plexiform layer by its co-localization with gephyrin, the gamma2
      subunit of the GABAA receptor and glycine receptors. YFP-NL2 puncta were apposed
      to the vesicular inhibitory transmitter transporter VGAT but not to CtBP2, a
      marker of presynaptic ribbons found at bipolar cell terminals. Similar patterns
      of co-localization with synaptic markers were observed for endogenous NL2. We
      also verified that expression of YFP-NL2 in the transgenic line did not
      significantly alter spontaneous inhibitory synaptic transmission onto RGCs. Using
      these mice, we found that, on average, the density of inhibitory synapses on
      individual arbors increased gradually until eye opening (postnatal day 15). A
      small centro-peripheral gradient in density found in mature arbors was apparent
      at the earliest age we examined (postnatal day 8). Unexpectedly, the adult ratio
      of inhibitory/excitatory postsynaptic sites was rapidly attained, shortly after
      glutamatergic synaptogenesis commenced (postnatal day 7). CONCLUSION: Our
      observations suggest that bipolar and amacrine cell synaptogenesis onto RGCs
      appear coordinated to rapidly attain a balanced ratio of excitatory and
      inhibitory synapse densities prior to the onset of visual experience.

PMID- 21864335
TI  - Measuring client satisfaction and the quality of family planning services: a
      comparative analysis of public and private health facilities in Tanzania, Kenya
      and Ghana.
AB  - BACKGROUND: Public and private family planning providers face different incentive
      structures, which may affect overall quality and ultimately the acceptability of
      family planning for their intended clients. This analysis seeks to quantify
      differences in the quality of family planning (FP) services at public and private
      providers in three representative sub-Saharan African countries (Tanzania, Kenya
      and Ghana), to assess how these quality differentials impact upon FP clients'
      satisfaction, and to suggest how quality improvements can improve contraceptive
      continuation rates. METHODS: Indices of technical, structural and process
      measures of quality are constructed from Service Provision Assessments (SPAs)
      conducted in Tanzania (2006), Kenya (2004) and Ghana (2002) using direct
      observation of facility attributes and client-provider interactions. Marginal
      effects from multivariate regressions controlling for client characteristics and
      the multi-stage cluster sample design assess the relative importance of different
      measures of structural and process quality at public and private facilities on
      client satisfaction. RESULTS: Private health facilities appear to be of higher
      (interpersonal) process quality than public facilities but not necessarily higher
      technical quality in the three countries, though these differentials are
      considerably larger at lower level facilities (clinics, health centers,
      dispensaries) than at hospitals. Family planning client satisfaction, however,
      appears considerably higher at private facilities - both hospitals and clinics -
      most likely attributable to both process and structural factors such as shorter
      waiting times and fewer stockouts of methods and supplies. CONCLUSIONS: Because
      the public sector represents the major source of family planning services in
      developing countries, governments and Ministries of Health should continue to
      implement and to encourage incentives, perhaps performance-based, to improve
      quality at public sector health facilities, as well as to strengthen regulatory
      and monitoring structures to ensure quality at both public and private
      facilities. In the meantime, private providers appear to be fulfilling an
      important gap in the provision of FP services in these countries.

PMID- 21864336
TI  - Central venous catheter-related bacteremia caused by Kocuria kristinae: case
      report and review of the literature.
AB  - Kocuria species are unusual human pathogens isolated most commonly from
      immunocompromised hosts, such as transplant recipients and cancer patients
      undergoing chemotherapy, or from patients with chronic medical conditions. A case
      of catheter-related bacteremia with pulmonary septic emboli in a pregnant adult
      female without chronic medical conditions is described. A review of other
      reported Kocuria infections is provided.

PMID- 21864337
TI  - Simvastatin inhibits TGFbeta1-induced fibronectin in human airway fibroblasts.
AB  - BACKGROUND: Bronchial fibroblasts contribute to airway remodelling, including
      airway wall fibrosis. Transforming growth factor (TGF)-beta1 plays a major role
      in this process. We previously revealed the importance of the mevalonate cascade
      in the fibrotic response of human airway smooth muscle cells. We now investigate
      mevalonate cascade-associated signaling in TGFbeta1-induced fibronectin
      expression by bronchial fibroblasts from non-asthmatic and asthmatic subjects.
      METHODS: We used simvastatin (1-15 MUM) to inhibit 3-hydroxy-3-methlyglutaryl
      coenzyme A (HMG-CoA) reductase which converts HMG-CoA to mevalonate. Selective
      inhibitors of geranylgeranyl transferase-1 (GGT1; GGTI-286, 10 MUM) and farnesyl
      transferase (FT; FTI-277, 10 MUM) were used to determine whether GGT1 and FT
      contribute to TGFbeta1-induced fibronectin expression. In addition, we studied
      the effects of co-incubation with simvastatin and mevalonate (1 mM),
      geranylgeranylpyrophosphate (30 MUM) or farnesylpyrophosphate (30 MUM). RESULTS:
      Immunoblotting revealed concentration-dependent simvastatin inhibition of
      TGFbeta1 (2.5 ng/ml, 48 h)-induced fibronectin. This was prevented by exogenous
      mevalonate, or isoprenoids (geranylgeranylpyrophosphate or
      farnesylpyrophosphate). The effects of simvastatin were mimicked by GGTI-286, but
      not FTI-277, suggesting fundamental involvement of GGT1 in TGFbeta1-induced
      signaling. Asthmatic fibroblasts exhibited greater TGFbeta1-induced fibronectin
      expression compared to non-asthmatic cells; this enhanced response was
      effectively reduced by simvastatin. CONCLUSIONS: We conclude that TGFbeta1
      induced fibronectin expression in airway fibroblasts relies on activity of GGT1
      and availability of isoprenoids. Our results suggest that targeting regulators of
      isoprenoid-dependent signaling holds promise for treating airway wall fibrosis.

PMID- 21864338
TI  - Characterization of the latent membrane protein 1 signaling complex of Epstein
      Barr virus in the membrane of mammalian cells with bimolecular fluorescence
      complementation.
AB  - BACKGROUND: Bimolecular fluorescence complementation (BiFC) is a novel technique
      to examine protein-protein interaction through the assembly of fluorescent
      proteins. In the present study, BiFC was used to study the assembly of the
      Epstein-Barr virus latent membrane protein 1 (LMP1) signaling complex within the
      membrane of mammalian cells. LMP1 signaling requires oligomerization,
      localization to lipid rafts, and association of the cytoplasmic domain to adaptor
      proteins, such as the tumor necrosis factor receptor associated factors (TRAFs).
      METHODS: LMP1-TRAF and LMP1-LMP1 interactions were assayed by BiFC using
      fluorescence microscopy and flow cytometry. Function of LMP1 BiFC contructs were
      confirmed by transformation assays and nuclear factor- kappaB (NF-kappaB)
      reporter assays. RESULTS: BiFC was observed between LMP1 and TRAF2 or TRAF3 and
      mutation of the LMP1 signaling domains reduced complementation. Fluorescence was
      observed in previously described LMP1 signaling locations. Oligomerization of
      LMP1 with itself induced complementation and BiFC. LMP1-BiFC constructs were
      fully functional in rodent fibroblast transformation assays and activation of NF
      kappaB reporter activity. The BiFC domain partially suppressed some LMP1 mutant
      phenotypes. CONCLUSIONS: Together these data suggest that BiFC is a unique and
      novel platform to identify and characterize proteins recruited to the LMP1
      signaling complex.

PMID- 21864339
TI  - The efficacy of oral brush biopsy with computer-assisted analysis in identifying
      precancerous and cancerous lesions.
AB  - BACKGROUND: Cancer of the oral cavity is the sixth most common malignancy
      reported worldwide and one with the highest mortality rate among all
      malignancies. There is a paucity of reliable diagnostic methods to detect early
      malignancies. This study was performed to evaluate the sensitivity and
      specificity of brush biopsy in identifying oral premalignant and malignant
      lesions. METHODS: Oral brush and scalpel biopsies were performed on 85
      consecutive patients presenting with an oral lesion deemed to be minimally
      suspicious by clinical examination and the results were compared. RESULTS: Of 79
      patients with adequate brush biopsy samples with matching scalpel biopsies, 27
      revealed histopathologic evidence of dysplasia or carcinoma, 26 of which were
      independently identified with the oral brush biopsy (sensitivity: 96.3%-95% CI,
      87%-100%). 52 oral lesions did not reveal any histopathologic evidence of
      dysplasia or carcinoma and of these, brush biopsy reported 47 as "negative" and 5
      as "atypical"(specificity of "positive" brush biopsy result is 100%- 95% CI, 93%
      100%; specificity for "atypical" brush biopsy result is 90.4%-95% CI, 82%-97%.
      The positive predictive value of an abnormal oral brush biopsy was 84% and the
      negative predictive value was 98%. CONCLUSION: Our study demonstrated that the
      oral brush biopsy is an accurate test in identifying oral premalignant and
      malignant lesions, even if minimally suspicious.

PMID- 21864340
TI  - Environmental versatility promotes modularity in genome-scale metabolic networks.
AB  - BACKGROUND: The ubiquity of modules in biological networks may result from an
      evolutionary benefit of a modular organization. For instance, modularity may
      increase the rate of adaptive evolution, because modules can be easily combined
      into new arrangements that may benefit their carrier. Conversely, modularity may
      emerge as a by-product of some trait. We here ask whether this last scenario may
      play a role in genome-scale metabolic networks that need to sustain life in one
      or more chemical environments. For such networks, we define a network module as a
      maximal set of reactions that are fully coupled, i.e., whose fluxes can only vary
      in fixed proportions. This definition overcomes limitations of purely graph based
      analyses of metabolism by exploiting the functional links between reactions. We
      call a metabolic network viable in a given chemical environment if it can
      synthesize all of an organism's biomass compounds from nutrients in this
      environment. An organism's metabolism is highly versatile if it can sustain life
      in many different chemical environments. We here ask whether versatility affects
      the modularity of metabolic networks. RESULTS: Using recently developed
      techniques to randomly sample large numbers of viable metabolic networks from a
      vast space of metabolic networks, we use flux balance analysis to study in silico
      metabolic networks that differ in their versatility. We find that highly
      versatile networks are also highly modular. They contain more modules and more
      reactions that are organized into modules. Most or all reactions in a module are
      associated with the same biochemical pathways. Modules that arise in highly
      versatile networks generally involve reactions that process nutrients or closely
      related chemicals. We also observe that the metabolism of E. coli is
      significantly more modular than even our most versatile networks. CONCLUSIONS:
      Our work shows that modularity in metabolic networks can be a by-product of
      functional constraints, e.g., the need to sustain life in multiple environments.
      This organizational principle is insensitive to the environments we consider and
      to the number of reactions in a metabolic network. Because we observe this
      principle not just in one or few biological networks, but in large random samples
      of networks, we propose that it may be a generic principle of metabolic network
      organization.

PMID- 21864341
TI  - Enzymatic synthesis of long double-stranded DNA labeled with haloderivatives of
      nucleobases in a precisely pre-determined sequence.
AB  - BACKGROUND: Restriction endonucleases are widely applied in recombinant DNA
      technology. Among them, enzymes of class IIS, which cleave DNA beyond recognition
      sites, are especially useful. We use BsaI enzyme for the pinpoint introduction of
      halogen nucleobases into DNA. This has been done for the purpose of anticancer
      radio- and phototherapy that is our long-term objective. RESULTS: An enzymatic
      method for synthesizing long double-stranded DNA labeled with the halogen
      derivatives of nucleobases (Hal-NBs) with 1-bp accuracy has been put forward and
      successfully tested on three different DNA fragments containing the 5-bromouracil
      (5-BrU) residue. The protocol assumes enzymatic cleavage of two Polymerase-Chain
      Reaction (PCR) fragments containing two recognition sequences for the same or
      different class IIS restriction endonucleases, where each PCR fragment has a
      partially complementary cleavage site. These sites are introduced using synthetic
      DNA primers or are naturally present in the sequence used. The cleavage sites are
      not compatible, and therefore not susceptible to ligation until they are
      partially filled with a Hal-NB or original nucleobase, resulting in complementary
      cohesive end formation. Ligation of these fragments ultimately leads to the
      required Hal-NB-labeled DNA duplex. With this approach, a synthetic, extremely
      long DNA fragment can be obtained by means of a multiple assembly reaction (n *
      maximum PCR product length: n * app. 50 kb). CONCLUSIONS: The long, precisely
      labeled DNA duplexes obtained behave in very much the same manner as natural DNA
      and are beyond the range of chemical synthesis. Moreover, the conditions of
      synthesis closely resemble the natural ones, and all the artifacts accompanying
      the chemical synthesis of DNA are thus eliminated. The approach proposed seems to
      be completely general and could be used to label DNA at multiple pre-determined
      sites and with halogen derivatives of any nucleobase. Access to DNAs labeled with
      Hal-NBs at specific position is an indispensable condition for the understanding
      and optimization of DNA photo- and radio-degradation, which are prerequisites for
      clinical trials of Hal-NBs in anticancer therapy.

PMID- 21864342
TI  - Are old running shoes detrimental to your feet? A pedobarographic study.
AB  - BACKGROUND: Footwear characteristics have been implicated in fatigue and foot
      pain. The recommended time for changing running shoes is every 500 miles. The aim
      of our study was to assess and compare plantar peak pressures and pressure time
      integrals in new and old running shoes. FINDINGS: This was a prospective study
      involving 11 healthy female volunteers with no previous foot and ankle problems.
      New running shoes were provided to the participants. Plantar pressures were
      measured using the Novel Pedar system while walking with new and participants'
      personal old running shoes. Plantar pressures were measured in nine areas of the
      feet. Demographic data, age of old running shoes, Body Mass Index (BMI), peak
      pressures and pressure-time integral were acquired. The right and left feet were
      selected at random and assessed separately. Statistical analysis was done using
      the paired t test to compare measurements between old and new running shoes.The
      mean peak pressures were higher in new running shoes (330.5 +/- 79.6 kiloPascals
      kPa) when compared to used old running shoes (304 +/- 58.1 kPa) (p = 0.01). The
      pressure-time integral was significantly higher in the new running shoes (110 +/-
      28.3 kPa s) compared to used old running shoes (100.7 +/- 24.0 kPa s) (p = 0.01).
      CONCLUSION: Plantar pressure measurements in general were higher in new running
      shoes. This could be due to the lack of flexibility in new running shoes. The
      risk of injury to the foot and ankle would appear to be higher if running shoes
      are changed frequently. We recommend breaking into new running shoes slowly using
      them for mild physical activity.

PMID- 21864344
TI  - Issues and special features of animal health research.
AB  - In the rapidly changing context of research on animal health, INRA launched a
      collective discussion on the challenges facing the field, its distinguishing
      features, and synergies with biomedical research. As has been declared forcibly
      by the heads of WHO, FAO and OIE, the challenges facing animal health, beyond
      diseases transmissible to humans, are critically important and involve food
      security, agriculture economics, and the ensemble of economic activities
      associated with agriculture. There are in addition issues related to public
      health (zoonoses, xenobiotics, antimicrobial resistance), the environment, and
      animal welfare.Animal health research is distinguished by particular
      methodologies and scientific questions that stem from the specific biological
      features of domestic species and from animal husbandry practices. It generally
      does not explore the same scientific questions as research on human biology, even
      when the same pathogens are being studied, and the discipline is rooted in a very
      specific agricultural and economic context.Generic and methodological synergies
      nevertheless exist with biomedical research, particularly with regard to tools
      and biological models. Certain domestic species furthermore present more
      functional similarities with humans than laboratory rodents.The singularity of
      animal health research in relation to biomedical research should be taken into
      account in the organization, evaluation, and funding of the field through a
      policy that clearly recognizes the specific issues at stake. At the same time,
      the One Health approach should facilitate closer collaboration between biomedical
      and animal health research at the level of research teams and programmes.

PMID- 21864343
TI  - A cluster-randomized trial of mass drug administration with a gametocytocidal
      drug combination to interrupt malaria transmission in a low endemic area in
      Tanzania.
AB  - BACKGROUND: Effective mass drug administration (MDA) with anti-malarial drugs can
      clear the human infectious reservoir for malaria and thereby interrupt malaria
      transmission. The likelihood of success of MDA depends on the intensity and
      seasonality of malaria transmission, the efficacy of the intervention in rapidly
      clearing all malaria parasite stages and the degree to which symptomatic and
      asymptomatic parasite carriers participate in the intervention. The impact of MDA
      with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus
      artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria
      transmission was determined in an area of very low and seasonal malaria
      transmission in northern Tanzania. METHODS: In a cluster-randomized trial in four
      villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster
      size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight
      clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over
      three days. Intervention and control clusters were 1 km apart; households that
      were located between clusters were treated as buffer zones where all individuals
      received SP+AS+PQ but were not selected for the evaluation. Passive case
      detection was done for the entire cohort and active case detection in 149
      children aged 1-10 year from the intervention arm and 143 from the control arm.
      Four cross-sectional surveys assessed parasite carriage by microscopy and
      molecular methods during a five-month follow-up period. RESULTS: The coverage
      rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by
      molecular detection methods was 2.2-2.7% prior to the intervention and
      undetectable during follow-up in both the control and intervention clusters. None
      of the slides collected during cross-sectional surveys had microscopically
      detectable parasite densities. Three clinical malaria episodes occurred in the
      intervention (n = 1) and control clusters (n = 2). CONCLUSIONS: This study
      illustrates the possibility to achieve high coverage with a three-day
      intervention but also the difficulty in defining suitable outcome measures to
      evaluate interventions in areas of very low malaria transmission intensity. The
      decline in transmission intensity prior to the intervention made it impossible to
      assess the impact of MDA in the chosen study setting. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00509015.

PMID- 21864345
TI  - A quantitative account of genomic island acquisitions in prokaryotes.
AB  - BACKGROUND: Microbial genomes do not merely evolve through the slow accumulation
      of mutations, but also, and often more dramatically, by taking up new DNA in a
      process called horizontal gene transfer. These innovation leaps in the
      acquisition of new traits can take place via the introgression of single genes,
      but also through the acquisition of large gene clusters, which are termed Genomic
      Islands. Since only a small proportion of all the DNA diversity has been
      sequenced, it can be hard to find the appropriate donors for acquired genes via
      sequence alignments from databases. In contrast, relative oligonucleotide
      frequencies represent a remarkably stable genomic signature in prokaryotes, which
      facilitates compositional comparisons as an alignment-free alternative for
      phylogenetic relatedness. In this project, we test whether Genomic Islands
      identified in individual bacterial genomes have a similar genomic signature, in
      terms of relative dinucleotide frequencies, and can therefore be expected to
      originate from a common donor species. RESULTS: When multiple Genomic Islands are
      present within a single genome, we find that up to 28% of these are
      compositionally very similar to each other, indicative of frequent recurring
      acquisitions from the same donor to the same acceptor. CONCLUSIONS: This
      represents the first quantitative assessment of common directional transfer
      events in prokaryotic evolutionary history. We suggest that many of the resident
      Genomic Islands per prokaryotic genome originated from the same source, which may
      have implications with respect to their regulatory interactions, and for the
      elucidation of the common origins of these acquired gene clusters.

PMID- 21864346
TI  - HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to
      the maturation inhibitor bevirimat.
AB  - BACKGROUND: Maturation inhibitors are an experimental class of antiretrovirals
      that inhibit Human Immunodeficiency Virus (HIV) particle maturation, the
      structural rearrangement required to form infectious virus particles. This
      rearrangement is triggered by the ordered cleavage of the precursor Gag
      polyproteins into their functional counterparts by the viral enzyme protease. In
      contrast to protease inhibitors, maturation inhibitors impede particle maturation
      by targeting the substrate of protease (Gag) instead of the protease enzyme
      itself. Direct cross-resistance between protease and maturation inhibitors may
      seem unlikely, but the co-evolution of protease and its substrate, Gag, during
      protease inhibitor therapy, could potentially affect future maturation inhibitor
      therapy. Previous studies showed that there might also be an effect of protease
      inhibitor resistance mutations on the development of maturation inhibitor
      resistance, but the exact mechanism remains unclear. We used wild-type and
      protease inhibitor resistant viruses to determine the impact of protease
      inhibitor resistance mutations on the development of maturation inhibitor
      resistance. RESULTS: Our resistance selection studies demonstrated that the
      resistance profiles for the maturation inhibitor bevirimat are more diverse for
      viruses with a mutated protease compared to viruses with a wild-type protease.
      Viral replication did not appear to be a major factor during emergence of
      bevirimat resistance. In all in vitro selections, one of four mutations was
      selected: Gag V362I, A364V, S368N or V370A. The impact of these mutations on
      maturation inhibitor resistance and viral replication was analyzed in different
      protease backgrounds. The data suggest that the protease background affects
      development of HIV-1 resistance to bevirimat and the replication profiles of
      bevirimat-selected HIV-1. The protease-dependent bevirimat resistance and
      replication levels can be explained by differences in CA/p2 cleavage processing
      by the different proteases. CONCLUSIONS: These findings highlight the complicated
      interactions between the viral protease and its substrate. By providing a better
      understanding of these interactions, we aim to help guide the development of
      second generation maturation inhibitors.

PMID- 21864347
TI  - Long-term survivor of relapsed MFH on the thigh treated with autologous formalin
      fixed tumor vaccine (AFTV) combined with limb-sparing surgery and radiotherapy.
AB  - Malignant fibrous histiocytoma (MFH) is an aggressive spindle cell cancer of soft
      tissue sarcoma type in the elderly, mostly affecting the extremities. Lesions > 5
      cm, positive margins, and local recurrence are significant poor prognostic
      indicators. The strongest predictor for distant metastasis was tumor size (> 5
      cm), and for overall survival, presence of local recurrence. Limb-sparing
      extensive tumor resection is preferred to achieve negative surgical margins.
      However, in some circumstances, amputation is inevitable. Recent studies
      demonstrated that adjuvant radiotherapy for microscopically positive surgical
      margins significantly improved local control and disease-free survival rates.
      Therefore, effective therapeutic strategies against locally relapsed high grade
      MFH are required to prevent distant metastasis and to achieve long-term disease
      free survival. Here, we report local relapse of high grade MFH treated by
      successive application of autologous formalin-fixed tumor vaccination (AFTV) with
      limb-sparing surgery and postoperative radiotherapy. The patient is alive and
      well, disease-free and with no functional impairment, more than five years after
      treatment.

PMID- 21864348
TI  - An ex vivo, assessor blind, randomised, parallel group, comparative efficacy
      trial of the ovicidal activity of three pediculicides after a single application-
      melaleuca oil and lavender oil, eucalyptus oil and lemon tea tree oil, and a
      "suffocation" pediculicide.
AB  - BACKGROUND: There are two components to the clinical efficacy of pediculicides:
      (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy
      against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy
      are confounded in clinical trials. Here we report on a trial that was specially
      designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were
      collected, pre-treatment and post-treatment, from subjects with different types
      of hair, different coloured hair and hair of different length. METHOD: Subjects
      with at least 20 live eggs of Pediculus capitis (head lice) were randomised to
      one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and
      lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil
      pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22
      live eggs were taken from the head by cutting the single hair with the live egg
      attached, before the treatment (total of 1,062 eggs). TREATMENT: The subjects
      then received a single treatment of one of the three pediculicides, according to
      the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were
      taken from the head by cutting the single hair with the egg attached (total of
      1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had
      hatched after 14 days in the pre-treatment group was compared with the proportion
      of eggs that hatched in the post-treatment group. The primary outcome measure was
      % ovicidal efficacy for each of the three pediculicides. RESULTS: 722 subjects
      were examined for the presence of eggs of head lice. 92 of these subjects were
      recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the
      melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and
      lemon tea tree oil pediculicide (n = 30 subjects). The group treated with
      eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%)
      whereas the group treated with melaleuca oil and lavender oil had an ovicidal
      efficacy of 44.4% (SD 23%) and the group treated with the "suffocation"
      pediculicide had an ovicidal efficacy of 68.3% (SD 38%). CONCLUSION: Ovicidal
      efficacy varied substantially among treatments, from 3.3% to 68.3%. The
      "suffocation" pediculicide and the melaleuca oil and lavender oil pediculicide
      (TTO/LO) were significantly more ovicidal than eucalyptus oil and lemon tea tree
      oil pediculicide (EO/LTTO) (P < 0.0001). Ranking: 1. "Suffocation" pediculicide
      (68.3% efficacy against eggs); 2. Melaleuca oil and lavender oil (44.4%)
      pediculicide; 3. Eucalyptus oil and lemon tea tree oil (3.3%) pediculicide. The
      "suffocation" pediculicide and TTO/LO are also highly efficacious against the
      crawling-stages. Thus, the "suffocation" pediculicide and TTO/LO should be
      recommended as first line treatments.

PMID- 21864349
TI  - Dimensionality and scale properties of the Edinburgh Depression Scale (EDS) in
      patients with type 2 diabetes mellitus: the DiaDDzoB study.
AB  - BACKGROUND: Depression is a common complication in type 2 diabetes (DM2),
      affecting 10-30% of patients. Since depression is underrecognized and
      undertreated, it is important that reliable and validated depression screening
      tools are available for use in patients with DM2. The Edinburgh Depression Scale
      (EDS) is a widely used method for screening depression. However, there is still
      debate about the dimensionality of the test. Furthermore, the EDS was originally
      developed to screen for depression in postpartum women. Empirical evidence that
      the EDS has comparable measurement properties in both males and females suffering
      from diabetes is lacking however. METHODS: In a large sample (N = 1,656) of
      diabetes patients, we examined: (1) dimensionality; (2) gender-related item bias;
      and (3) the screening properties of the EDS using factor analysis and item
      response theory. RESULTS: We found evidence that the ten EDS items constitute a
      scale that is essentially one dimensional and has adequate measurement
      properties. Three items showed differential item functioning (DIF), two of them
      showed substantial DIF. However, at the scale level, DIF had no practical impact.
      Anhedonia (the inability to be able to laugh or enjoy) and sleeping problems were
      the most informative indicators for being able to differentiate between the
      diagnostic groups of mild and severe depression. CONCLUSIONS: The EDS constitutes
      a sound scale for measuring an attribute of general depression. Persons can be
      reliably measured using the sum score. Screening rules for mild and severe
      depression are applicable to both males and females.

PMID- 21864350
TI  - Effort, reward and self-reported mental health: a simulation study on negative
      affectivity bias.
AB  - BACKGROUND: In the present article, we propose an alternative method for dealing
      with negative affectivity (NA) biases in research, while investigating the
      association between a deleterious psychosocial environment at work and poor
      mental health. First, we investigated how strong NA must be to cause an observed
      correlation between the independent and dependent variables. Second, we
      subjectively assessed whether NA can have a large enough impact on a large enough
      number of subjects to invalidate the observed correlations between dependent and
      independent variables. METHODS: We simulated 10,000 populations of 300 subjects
      each, using the marginal distribution of workers in an actual population that had
      answered the Siegrist's questionnaire on effort and reward imbalance (ERI) and
      the General Health Questionnaire (GHQ). RESULTS: The results of the present study
      suggested that simulated NA has a minimal effect on the mean scores for effort
      and reward. However, the correlations between the effort and reward imbalance
      (ERI) ratio and the GHQ score might be important, even in simulated populations
      with a limited NA. CONCLUSIONS: When investigating the relationship between the
      ERI ratio and the GHQ score, we suggest the following rules for the
      interpretation of the results: correlations with an explained variance of 5% and
      below should be considered with caution; correlations with an explained variance
      between 5% and 10% may result from NA, although this effect does not seem likely;
      and correlations with an explained variance of 10% and above are not likely to be
      the result of NA biases.

PMID- 21864351
TI  - Drosophila selenophosphate synthetase 1 regulates vitamin B6 metabolism:
      prediction and confirmation.
AB  - BACKGROUND: There are two selenophosphate synthetases (SPSs) in higher
      eukaryotes, SPS1 and SPS2. Of these two isotypes, only SPS2 catalyzes
      selenophosphate synthesis. Although SPS1 does not contain selenophosphate
      synthesis activity, it was found to be essential for cell growth and
      embryogenesis in Drosophila. The function of SPS1, however, has not been
      elucidated. RESULTS: Differentially expressed genes in Drosophila SL2 cells were
      identified using two-way analysis of variance methods and clustered according to
      their temporal expression pattern. Gene ontology analysis was performed against
      differentially expressed genes and gene ontology terms related to vitamin B6
      biosynthesis were found to be significantly affected at the early stage at which
      megamitochondria were not formed (day 3) after SPS1 knockdown. Interestingly,
      genes related to defense and amino acid metabolism were affected at a later stage
      (day 5) following knockdown. Levels of pyridoxal phosphate, an active form of
      vitamin B6, were decreased by SPS1 knockdown. Treatment of SL2 cells with an
      inhibitor of pyridoxal phosphate synthesis resulted in both a similar pattern of
      expression as that found by SPS1 knockdown and the formation of megamitochondria,
      the major phenotypic change observed by SPS1 knockdown. CONCLUSIONS: These
      results indicate that SPS1 regulates vitamin B6 synthesis, which in turn impacts
      various cellular systems such as amino acid metabolism, defense and other
      important metabolic activities.

PMID- 21864352
TI  - Displaced midshaft fractures of the clavicle: non-operative treatment versus
      plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial.
AB  - BACKGROUND: The traditional view that the vast majority of midshaft clavicular
      fractures heal with good functional outcomes following non-operative treatment
      may be no longer valid for all midshaft clavicular fractures. Recent studies have
      presented a relatively high incidence of non-union and identified speciic
      limitations of the shoulder function in subgroups of patients with these
      injuries. AIM: A prospective, multicentre randomised controlled trial (RCT) will
      be conducted in 21 hospitals in the Netherlands, comparing fracture consolidation
      and shoulder function after either non-operative treatment with a sling or a
      plate fixation. METHODS/DESIGN: A total of 350 patients will be included, between
      18 and 60 years of age, with a dislocated midshaft clavicular fracture. The
      primary outcome is the incidence of non-union, which will be determined with
      standardised X-rays (Antero-Posterior and 30 degrees caudocephalad view).
      Secondary outcome will be the functional outcome, measured using the Constant
      Score. Strength of the shoulder muscles will be measured with a handheld
      dynamometer (MicroFET2). Furthermore, the health-related Quality of Life score
      (ShortForm-36) and the Disabilities of Arm, Shoulder and Hand (DASH) Outcome
      Measure will be monitored as subjective parameters. Data on complications, bone
      union, cosmetic aspects and use of painkillers will be collected with follow-up
      questionnaires. The follow-up time will be two years. All patients will be
      monitored at regular intervals over the subsequent twelve months (two and six
      weeks, three months and one year). After two years an interview by telephone and
      a written survey will be performed to evaluate the two-year functional and
      mechanical outcomes. All data will be analysed on an intention-to-treat basis,
      using univariate and multivariate analyses. DISCUSSION: This trial will provide
      level-1 evidence for the comparison of consolidation and functional outcome
      between two standardised treatment options for dislocated midshaft clavicular
      fractures. The gathered data may support the development of a clinical guideline
      for treatment of clavicular fractures. TRIAL REGISTRATION: Netherlands National
      Trial Register NTR2399.

PMID- 21864353
TI  - Group medical visits in the follow-up of women with a BRCA mutation: design of a
      randomized controlled trial.
AB  - BACKGROUND: BRCA mutation carriers have a 40-80% life-time risk of developing
      breast cancer. They may opt for yearly breast cancer surveillance or for
      prophylactic mastectomy. Both options show increased survival rates. It is a
      complex choice to be made between these two options. As a result most women
      experience high levels of distress and high needs for information. To fulfill the
      needs for psychosocial support and information we have introduced group medical
      consultations (GMCs). A GMC provides individual medical visits conducted within a
      group. This 90 minute group-visit with 8-12 patients gives patients the
      opportunity to spend more time with their clinician and a behavioral health
      professional and learn from other patients experiencing similar topics. However,
      it should be noted that group sessions may increase fear in some patients or
      influence their decision making. METHODS/DESIGN: In this randomized controlled
      trial, 160 BRCA mutation carriers diagnosed maximally 2 years ago are recruited
      from the Radboud University Nijmegen Medical Centre. Participants are randomized
      in a 1:1 ratio to either the GMC intervention group (onetime participation in a
      GMC instead of a standard individual visit) or to a usual care control group.
      Primary outcome measures are empowerment and psychological distress (SCL 90).
      Secondary outcome measures are fear of cancer, information needs before the
      consultation and the received information, self-examination of the breasts,
      patient satisfaction, quality of life and cost-effectiveness. Data are collected
      via self-reported questionnaires 1 week before the visit, and at 1 week and at 3
      months follow-up. A pilot study was conducted to test all procedures and
      questionnaires. DISCUSSION: The possibility for interaction with other BRCA
      mutation carriers within a medical visit is unique. This study will assess the
      effectiveness of GMCs for BRCA mutation carriers to improve empowerment and
      decrease distress compared to individual visits. If GMCs prove to be effective
      and efficient, implementation of GMCs in regular care for BRCA mutation carriers
      will be recommended.

PMID- 21864356
TI  - A successfully thrombolysed acute inferior myocardial infarction due to type A
      aortic dissection with lethal consequences: the importance of early cardiac
      echocardiography.
AB  - Thrombolysis, a standard therapy for ST elevation myocardial infarction (STEMI)
      in non-PCI-capable hospitals, may be catastrophic for patients with aortic
      dissection leading to further expansion, rupture and uncontrolled bleeding.
      Stanford type A aortic dissection, rarely may mimic myocardial infarction. We
      report a case of a patient with an inferior STEMI thrombolysed with tenecteplase
      and followed by clinical and electrocardiographic evidence of successful
      reperfusion, which was found later to be a lethal acute aortic dissection.
      Prognostic implications of early diagnosis applying transthoracic
      echocardiography (TTE) are described.

PMID- 21864355
TI  - Clinical management of gastric cancer: results of a multicentre survey.
AB  - BACKGROUND: The National Comprehensive Cancer Network clinical practice
      guidelines in oncology-gastric cancer guidelines have been widely used to provide
      appropriate recommendations for the treatment of patients with gastric cancer.
      The aim of this study was to examine the adherence of surgical oncologists,
      medical oncologists, and radiation oncologists' to the recommended guidelines.
      METHODS: A questionnaire asking the treatment options for gastric cancer cases
      was sent to 394 Chinese oncology specialists, including surgical oncologists,
      medical oncologists, and radiation oncologists working in hospitals joined in The
      Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire
      involved a series of clinical scenarios regarding the interpretation of surgery,
      neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer.
      RESULTS: Analysis of 358 respondents (91%) showed variations between each
      specialization and from the recommended guidelines in the management approaches
      to specific clinical scenarios. The majority of specialists admitted that less
      than 50% of patients received multidisciplinary evaluation before treatment. The
      participants gave different responses to questions involving adjuvant,
      neoadjuvant, and advanced settings, compared to the recommended guidelines.
      CONCLUSIONS: These results highlight the heterogeneity of the treatment of
      gastric cancer. Surgical oncologists, medical oncologists, and radiation
      oncologists are not adhering to the recommended guidelines.

PMID- 21864354
TI  - Roles of planar cell polarity pathways in the development of neural [correction
      of neutral] tube defects.
AB  - Neural tube defects (NTDs) are the second most common birth defect in humans.
      Despite many advances in the understanding of NTDs and the identification of many
      genes related to NTDs, the fundamental etiology for the majority of cases of NTDs
      remains unclear. Planar cell polarity (PCP) signaling pathway, which is important
      for polarized cell movement (such as cell migration) and organ morphogenesis
      through the activation of cytoskeletal pathways, has been shown to play multiple
      roles during neural tube closure. The disrupted function of PCP pathway is
      connected with some NTDs. Here, we summarize our current understanding of how PCP
      factors affect the pathogenesis of NTDs.

PMID- 21864357
TI  - The association between polyunsaturated fatty acids and depression among Iranian
      postgraduate students in Malaysia.
AB  - BACKGROUND: The incidence of depression is expected to increase over the next 20
      years, and many people will have to deal with it. It has been reported that up to
      40% of university students experience levels of depression. Several negative
      consequences are associated with depression symptoms, such as memory impairment,
      suicide, and substance abuse. Recently, researchers have been studying possible
      associations between depression and polyunsaturated fatty acids (PUFAs), which
      may modify depression symptoms. The aim of the present study was to find an
      association between PUFA levels and depression among Iranian postgraduate
      students in Malaysia. METHODS: This cross-sectional study was conducted in 2011
      with 402 Iranian postgraduate students who were studying in Malaysia. The
      participants included 173 (43%) women and 229 (57%) men, and the mean age of the
      participants was 32.54 +/- 6.22 years. RESULTS: After adjustment for several
      potential confounders including sex, age, BMI, PUFAs, MUFAs, and SFAs, monthly
      expenses, close friends, living in campus, smoking, education, and marital status
      in a logistic regression model, an inverse relationship was found between
      depression symptoms and the dietary intake of PUFAs. CONCLUSION: We found an
      inverse association between PUFA intake and depression symptoms in Iranian
      postgraduate students in Malaysia. We, therefore, concluded that long-term intake
      of PUFAs may modify or prevent depression symptoms.

PMID- 21864358
TI  - Ensemble encoding of nociceptive stimulus intensity in the rat medial and lateral
      pain systems.
AB  - BACKGROUND: The ability to encode noxious stimulus intensity is essential for the
      neural processing of pain perception. It is well accepted that the intensity
      information is transmitted within both sensory and affective pathways. However,
      it remains unclear what the encoding patterns are in the thalamocortical brain
      regions, and whether the dual pain systems share similar responsibility in
      intensity coding. RESULTS: Multichannel single-unit recordings were used to
      investigate the activity of individual neurons and neuronal ensembles in the rat
      brain following the application of noxious laser stimuli of increasing intensity
      to the hindpaw. Four brain regions were monitored, including two within the
      lateral sensory pain pathway, namely, the ventral posterior lateral thalamic
      nuclei and the primary somatosensory cortex, and two in the medial pathway,
      namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex.
      Neuron number, firing rate, and ensemble spike count codings were examined in
      this study. Our results showed that the noxious laser stimulation evoked double
      peak responses in all recorded brain regions. Significant correlations were found
      between the laser intensity and the number of responsive neurons, the firing
      rates, as well as the mass spike counts (MSCs). MSC coding was generally more
      efficient than the other two methods. Moreover, the coding capacities of neurons
      in the two pathways were comparable. CONCLUSION: This study demonstrated the
      collective contribution of medial and lateral pathway neurons to the noxious
      intensity coding. Additionally, we provide evidence that ensemble spike count may
      be the most reliable method for coding pain intensity in the brain.

PMID- 21864359
TI  - Validity of estimating minute-by-minute energy expenditure of continuous walking
      bouts by accelerometry.
AB  - BACKGROUND: Objective measurement of physical activity remains an important
      challenge. For wearable monitors such as accelerometer-based physical activity
      monitors, more accurate methods are needed to convert activity counts into energy
      expenditure (EE). PURPOSE: The purpose of this study was to examine the accuracy
      of the refined Crouter 2-Regression Model (C2RM) for estimating EE during the
      transition from rest to walking and walking to rest. A secondary purpose was to
      determine the extent of overestimation in minute-by-minute EE between the refined
      C2RM and the 2006 C2RM. METHODS: Thirty volunteers (age, 28 +/- 7.7 yrs)
      performed 15 minutes of seated rest, 8 minutes of over-ground walking, and 8
      minutes of seated rest. An ActiGraph GT1M accelerometer and Cosmed K4b2 portable
      metabolic system were worn during all activities. Participants were randomly
      assigned to start the walking bout at 0, 20, or 40 s into the minute (according
      to the ActiGraph clock). Acceleration data were analyzed by two methods: 2006
      Crouter model and a new refined model. RESULTS: The 2006 Crouter 2-Regression
      model over-predicted measured kcal kg-1 hr-1 during the first and last
      transitional minutes of the 20-s and 40-s walking conditions (P < 0.001). It also
      over-predicted the average EE for a walking bout (4.0 +/- 0.5 kcal kg-1 hr-1),
      compared to both the measured kcal kg-1 hr-1 (3.6 +/- 0.7 kcal kg-1 hr-1) and the
      refined Crouter model (3.5 +/- 0.5 kcal kg-1 hr-1) (P < 0.05). CONCLUSION: The
      2006 Crouter 2-regression model over-predicts EE at the beginning and end of
      walking bouts, due to high variability in accelerometer counts during the
      transitional minutes. The new refined model eliminates this problem and results
      in a more accurate prediction of EE during walking.

PMID- 21864360
TI  - Whole-genome phylogenies of the family Bacillaceae and expansion of the sigma
      factor gene family in the Bacillus cereus species-group.
AB  - BACKGROUND: The Bacillus cereus sensu lato group consists of six species (B.
      anthracis, B. cereus, B. mycoides, B. pseudomycoides, B. thuringiensis, and B.
      weihenstephanensis). While classical microbial taxonomy proposed these organisms
      as distinct species, newer molecular phylogenies and comparative genome
      sequencing suggests that these organisms should be classified as a single species
      (thus, we will refer to these organisms collectively as the Bc species-group).
      How do we account for the underlying similarity of these phenotypically diverse
      microbes? It has been established for some time that the most rapidly evolving
      and evolutionarily flexible portions of the bacterial genome are regulatory
      sequences and transcriptional networks. Other studies have suggested that the
      sigma factor gene family of these organisms has diverged and expanded
      significantly relative to their ancestors; sigma factors are those portions of
      the bacterial transcriptional apparatus that control RNA polymerase recognition
      for promoter selection. Thus, examining sigma factor divergence in these
      organisms would concurrently examine both regulatory sequences and
      transcriptional networks important for divergence. We began this examination by
      comparison to the sigma factor gene set of B. subtilis. RESULTS: Phylogenetic
      analysis of the Bc species-group utilizing 157 single-copy genes of the family
      Bacillaceae suggests that several taxonomic revisions of the genus Bacillus
      should be considered. Within the Bc species-group there is little indication that
      the currently recognized species form related sub-groupings, suggesting that they
      are members of the same species. The sigma factor gene family encoded by the Bc
      species-group appears to be the result of a dynamic gene-duplication and gene
      loss process that in previous analyses underestimated the true heterogeneity of
      the sigma factor content in the Bc species-group. CONCLUSIONS: Expansion of the
      sigma factor gene family appears to have preferentially occurred within the
      extracytoplasmic function (ECF) sigma factor genes, while the primary alternative
      (PA) sigma factor genes are, in general, highly conserved with those found in B.
      subtilis. Divergence of the sigma-controlled transcriptional regulons among
      various members of the Bc species-group likely has a major role in explaining the
      diversity of phenotypic characteristics seen in members of the Bc species-group.

PMID- 21864361
TI  - Antioxidants and breast cancer risk- a population-based case-control study in
      Canada.
AB  - BACKGROUND: The effect of antioxidants on breast cancer is still controversial.
      Our objective was to assess the association between antioxidants and breast
      cancer risk in a large population-based case-control study. METHODS: The study
      population included 2,362 cases with pathologically confirmed incident breast
      cancer (866 premenopausal and 1,496 postmenopausal) and 2,462 controls in Canada.
      Intakes of antioxidants from diet and from supplementation as well as other
      potential risk factors for breast cancer were collected by a self-reported
      questionnaire. RESULTS: Compared with subjects with no supplementation, 10 years
      or longer supplementation of zinc had multivariable-adjusted odds ratios (OR) and
      95% confidence intervals (CI) of 0.46 (0.25-0.85) for premenopausal women, while
      supplementation of 10 years or longer of multiple vitamin, beta-carotene, vitamin
      C, vitamin E and zinc had multivariable-adjusted ORs (95% CIs) of 0.74 (0.59,
      0.92), 0.58 (0.36, 0.95), 0.79 (0.63-0.99), 0.75 (0.58, 0.97), and 0.47 (0.28
      0.78), respectively, for postmenopausal women. No significant effect of
      antioxidants from dietary sources (including beta-carotene, alpha-carotene,
      lycopene, lutein and zeaxanthin, vitamin C, vitamin E, selenium and zinc) or from
      supplementation less than 10 years was observed. CONCLUSIONS: This study suggests
      that supplementation of zinc in premenopausal women, and supplementation of
      multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc in postmenopausal
      women for 10 or more years may protect women from developing breast cancer.
      However, we were unable to determine the overall effect of total dose or intake
      from both diet and supplement.

PMID- 21864362
TI  - Non-invasive interactive neurostimulation (InterXTM) reduces acute pain in
      patients following total knee replacement surgery: a randomised, controlled
      trial.
AB  - BACKGROUND: Adequate post-operative pain relief following total knee replacement
      (TKR) is very important to optimal post-operative recovery. Faster mobilisation
      and rehabilitation ultimately results in optimum recovery outcomes, but pain is
      often the limiting factor. This study evaluates the potential clinical benefit of
      the InterX neurostimulation device on pain reduction and rehabilitative outcome.
      METHODS: A clinical trial under the Hywel Dda Clinical Audit Committee to
      validate the clinical benefit of Non-invasive Interactive Neurostimulation (NIN)
      therapy using the InterX device was performed in patients undergoing TKR. 61
      patients were randomised to treatment groups in blocks of two from the Theatre
      Operation List. The control group received the standard hospital course of pain
      medication and rehabilitation twice daily for 3 post-op days. The experimental
      group received 8 sessions of NIN therapy over 3 post-op days in addition to the
      standard course received by the Control group. Pain and range of motion were
      collected as the primary study measures. RESULTS: Sixty one subjects were
      enrolled and randomised, but 2 subjects (one/group) were excluded due to missing
      data at Baseline/Final; one subject in the InterX group was excluded due to pre
      existing rheumatoid pain conditions confounding the analysis. The experimental
      group pre- to post-session Verbal Rating Scale for pain (VRS) showed that NIN
      therapy consistently reduced the pain scores by a mean of 2.3 points (SE 0.11).
      The NIN pre-treatment score at Final was used for the primary ANCOVA comparison,
      demonstrating a significantly greater cumulative treatment effect of a mean 2.2
      (SE 0.49) points pain reduction (p = 0.002). Control subjects only experienced a
      mean 0.34 (SE 0.49) point decrease in pain. Ninety degrees ROM was required to
      discharge the patient and this was attained as an average despite the greater
      Baseline deficit in the InterX group. Eight control patients and three
      experimental patients did not achieve this ROM. CONCLUSIONS: The results clearly
      demonstrated the clinical benefit of NIN therapy as a supplement to the standard
      rehabilitation protocol. The subjects receiving InterX fared significantly better
      clinically. Within a relatively short 3-day period of time, patients in the
      experimental group obtained the necessary ROM for discharge and did it
      experiencing lower levels of pain than those in the control group.

PMID- 21864363
TI  - The role of schools in the spread of mumps among unvaccinated children: a
      retrospective cohort study.
AB  - BACKGROUND: In the Netherlands, epidemics of vaccine preventable diseases are
      largely confined to an orthodox protestant minority with religious objections to
      vaccination. The clustering of unvaccinated children in orthodox protestant
      schools can foster the spread of epidemics. School closure has nevertheless not
      been practiced up until now. A mumps epidemic in 2007-2008 gave us an opportunity
      to study the role of schools in the spread of a vaccine preventable disease in a
      village with low vaccination coverage. METHODS: A retrospective cohort study was
      conducted among the students in four elementary schools and their siblings. The
      following information was collected for each child: having had the mumps or not
      and when, school, age, MMR vaccination status, household size, presence of high
      school students in the household, religious denomination, and home village. The
      spread of mumps among unvaccinated children was compared for the four schools in
      a Kaplan-Meier analysis using a log-rank test. Cox proportional hazard analyses
      were performed to test for the influence of other factors. To correct for
      confounding, a univariate Cox regression model with only school included as a
      determinant was compared to a multivariate regression model containing all
      possible confounders. RESULTS: Out of 650 households with children at the
      schools, 54% completed a questionnaire, which provided information on 1191
      children. For the unvaccinated children (N = 769), the Kaplan-Meier curves showed
      significant differences among the schools in their cumulative attack rates. After
      correction for confounding, the Cox regression analysis showed the hazard of
      mumps to be higher in one orthodox protestant school compared to the other
      (hazard ratio 1.43, p < 0.001). Household size independently influenced the
      hazard of mumps (hazard ratio 1.44, p < 0.005) with children in larger households
      running a greater risk. CONCLUSION: If and when unvaccinated children got mumps
      was determined by the particular school the children and their siblings attended,
      and by the household size. This finding suggests that school closure can
      influence the spread of an epidemic among orthodox protestant populations,
      provided that social distancing is adhered to as well. Further research on the
      effects of school closure on the final attack rate is nevertheless recommended.

PMID- 21864364
TI  - Health status convergence at the local level: empirical evidence from Austria.
AB  - INTRODUCTION: Health is an important dimension of welfare comparisons across
      individuals, regions and states. Particularly from a long-term perspective,
      within-country convergence of the health status has rarely been investigated by
      applying methods well established in other scientific fields. In the following
      paper we study the relation between initial levels of the health status and its
      improvement at the local community level in Austria in the time period 1969-2004.
      METHODS: We use age standardized mortality rates from 2381 Austrian communities
      as an indicator for the health status and analyze the convergence/divergence of
      overall mortality for (i) the whole population, (ii) females, (iii) males and
      (iv) the gender mortality gap. Convergence/Divergence is studied by applying
      different concepts of cross-regional inequality (weighted standard deviation,
      coefficient of variation, Theil-Coefficient of inequality). Various econometric
      techniques (weighted OLS, Quantile Regression, Kendall's Rank Concordance) are
      used to test for absolute and conditional beta-convergence in mortality. RESULTS:
      Regarding sigma-convergence, we find rather mixed results. While the weighted
      standard deviation indicates an increase in equality for all four variables, the
      picture appears less clear when correcting for the decreasing mean in the
      distribution. However, we find highly significant coefficients for absolute and
      conditional beta-convergence between the periods. While these results are
      confirmed by several robustness tests, we also find evidence for the existence of
      convergence clubs. CONCLUSIONS: The highly significant beta-convergence across
      communities might be caused by (i) the efforts to harmonize and centralize the
      health policy at the federal level in Austria since the 1970s, (ii) the
      diminishing returns of the input factors in the health production function, which
      might lead to convergence, as the general conditions (e.g. income, education
      etc.) improve over time, and (iii) the mobility of people across regions, as
      people tend to move to regions/communities which exhibit more favorable living
      conditions.JEL classification: I10, I12, I18.

PMID- 21864365
TI  - Factors associated with parental recognition of a child's overweight status--a
      cross sectional study.
AB  - BACKGROUND: Very few studies have evaluated the association between a child's
      lifestyle factors and their parent's ability to recognise the overweight status
      of their offspring. The aim of this study was to analyze the factors associated
      with a parent's ability to recognise their own offspring's overweight status.
      METHODS: 125 overweight children out of all 1,278 school beginners in Northern
      Finland were enrolled.Weight and height were measured in health care clinics.
      Overweight status was defined by BMI according to internationally accepted
      criteria. A questionnaire to be filled in by parents was delivered by the school
      nurses. The parents were asked to evaluate their offspring's weight status. The
      child's eating habits and physical activity patterns were also enquired about.
      Factor groups of food and physical activity habits were formed by factor
      analysis. Binary logistic regression was performed using all variables associated
      with recognition of overweight status in univariate analyses. The significant
      risk factors in the final model are reported using odds ratios (ORs) and their
      95% confidence intervals (CIs). RESULTS: Fifty-seven percent (69/120) of the
      parents of the overweight children considered their child as normal weight.
      Child's BMI was positively associated with parental recognition of overweight (OR
      3.59, CI 1.8 to 7.0). Overweight boys were less likely to be recognised than
      overweight girls (OR 0.14, CI 0.033 to 0.58). Child's healthy diet (OR 0.22, CI
      0.091 to 0.54) and high physical activity (OR 0.29, CI 0.11 to 0.79) were
      inversely related to parental recognition of overweight status. CONCLUSIONS:
      Child's healthy eating habits and physical activity are inversely related to
      parental recognition of their offspring's overweight. These should be taken into
      account when planning prevention and treatment strategies for childhood obesity.

PMID- 21864366
TI  - Pharmacogenomic technologies: a necessary "luxury" for better global public
      health?
AB  - BACKGROUND: Pharmacogenomic technologies aim to redirect drug development to
      increase safety and efficacy of individual care. There is much hope that their
      implementation in the drug development process will help respond to population
      health needs, particularly in developing countries. However, there is also fear
      that novel pharmacogenomic drugs will remain too costly, be designed for the
      needs of the wealthy nations, and so constitute an unnecessary "luxury" for most
      populations. In this paper, we analyse the promise that pharmacogenomic
      technologies hold for improving global public health and identify strategies and
      challenges associated with their implementation. DISCUSSION: This paper evaluates
      the capacity of pharmacogenomic technologies to meet six criteria described by
      the University of Toronto Joint Centre for Bioethics group: 1) impact of the
      technology, 2) technology appropriateness, 3) capacity to address local burdens,
      4) feasibility to be implemented in reasonable time, 5) capacity to reduce the
      knowledge gap, and 6) capacity for indirect benefits. We argue that the
      implementation of pharmacogenomic technologies in the drug development process
      can positively impact population health. However, this positive impact depends on
      how and for which purposes the technologies are used. We discuss the potential of
      these technologies to stimulate drug discovery in the case of rare (orphan
      diseases) or neglected diseases, but also to reduce acute adverse drug reactions
      in infectious disease treatment and prevention, which promises to improve global
      public health. CONCLUSIONS: The implementation of pharmacogenomic technologies
      may lead to the development of drugs that appear to be a "luxury" for populations
      in need of numerous interventions that are known to have a demonstrable impact on
      population health (e.g., secure access to potable water, reduction of social
      inequities, health education). However, our analysis shows that pharmacogenomic
      technologies do have the potential to redirect drug development and distribution
      so as to improve the health of vulnerable populations. Strategies should thus be
      developed to better direct their implementation towards meeting the needs and
      responding to the realities of populations of the developing world (i.e., social,
      cultural and political acceptability, and local health burdens), making
      pharmacogenomic technologies a necessary "luxury" for global public health.

PMID- 21864367
TI  - Datgan, a reusable software system for facile interrogation and visualization of
      complex transcription profiling data.
AB  - BACKGROUND: We introduce Glaucoma Discovery Platform (GDP), an online environment
      for facile visualization and interrogation of complex transcription profiling
      datasets for glaucoma. We also report the availability of Datgan, the suite of
      scripts that was developed to construct GDP. This reusable software system
      complements existing repositories such as NCBI GEO or EBI ArrayExpress as it
      allows the construction of searchable databases to maximize understanding of user
      selected transcription profiling datasets. DESCRIPTION: Datgan scripts were used
      to construct both the underlying data tables and the web interface that form GDP.
      GDP is populated using data from a mouse model of glaucoma. The data was
      generated using the DBA/2J strain, a widely used mouse model of glaucoma. The
      DBA/2J-Gpnmb+ strain provided a genetically matched control strain that does not
      develop glaucoma. We separately assessed both the retina and the optic nerve
      head, important tissues in glaucoma. We used hierarchical clustering to identify
      early molecular stages of glaucoma that could not be identified using
      morphological assessment of disease. GDP has two components. First, an
      interactive search and retrieve component provides the ability to assess gene(s)
      of interest in all identified stages of disease in both the retina and optic
      nerve head. The output is returned in graphical and tabular format with
      statistically significant differences highlighted for easy visual analysis.
      Second, a bulk download component allows lists of differentially expressed genes
      to be retrieved as a series of files compatible with Excel. To facilitate access
      to additional information available for genes of interest, GDP is linked to
      selected external resources including Mouse Genome Informatics and Online
      Medelian Inheritance in Man (OMIM). CONCLUSION: Datgan-constructed databases
      allow user-friendly access to datasets that involve temporally ordered stages of
      disease or developmental stages. Datgan and GDP are available from
      http://glaucomadb.jax.org/glaucoma.

PMID- 21864368
TI  - Upfront systemic chemotherapy and preoperative short-course radiotherapy with
      delayed surgery for locally advanced rectal cancer with distant metastases.
AB  - BACKGROUND: Choosing the most effective approach for treating rectal cancer with
      mesorectal fascia (MRF) involvement or closeness and synchronous distant
      metastases is a current clinical challenge. The aim of this retrospective study
      was to determine if upfront systemic chemotherapy and short-course radiotherapy
      (RT) with delayed surgery enables R0 resection. METHODS: Between March 2009 and
      October 2009, six patients were selected for upfront chemotherapy and short
      course RT (5 * 5 Gy) with delayed surgery. The patients had locally advanced
      primary tumors with MRF involvement or closeness, as well as synchronous and
      potentially resectable distant metastases. Chemotherapy was administered to five
      patients between the end of the RT and surgery. All patients underwent total
      mesorectal excision (TME). RESULTS: The median patient age was 54 years (range 39
      63). All primary and metastatic lesions were resected simultaneously. The median
      duration between short-course RT and surgery was 13 weeks (range, 7-18). R0
      resection of rectal lesions was achieved in 5 patients. One patient, who had a
      very low-lying tumor, had an R1 resection. The median follow-up duration for all
      patients was 16.7 months (range, 15.5-23.5). One patient developed liver
      metastasis at 15.7 months. There have been no local recurrences or deaths.
      CONCLUSIONS: Upfront chemotherapy and short course RT with delayed surgery is a
      valuable alternative treatment approach for patients with MRF involvement or
      closeness of rectal cancer with distant metastases.

PMID- 21864369
TI  - Inflammatory pseudotumor of the kidney: a case report.
AB  - INTRODUCTION: Inflammatory pseudotumors, also known as inflammatory
      myofibroblastic tumors, are uncommon benign tumors of unknown etiology which may
      develop at several anatomical sites. In the urogenital tract, inflammatory
      pseudotumor usually affects the urinary bladder or the prostate. Inflammatory
      pseudotumor of the kidney is very rare. It is considered as a reactive
      inflammatory lesion that features very good prognosis. CASE PRESENTATION: We
      present the case of a 57-year-old Moroccan man who presented with a two-month
      history of gross hematuria and left lumbar pain. Imaging investigations revealed
      a left kidney mass and pathological examination of the nephrectomy specimen
      showed an inflammatory pseudotumor. CONCLUSION: As the preoperative definitive
      diagnosis of such a tumor is not possible, surgery is advised because only
      pathological examination of the nephrectomy specimen can establish the diagnosis
      with certainty. From one case report and literature review, the authors suggest a
      diagnostic and therapeutic strategy for the management of this rare tumor.

PMID- 21864370
TI  - Psycho-education with problem solving (PEPS) therapy for adults with personality
      disorder: a pragmatic multi-site community-based randomised clinical trial.
AB  - BACKGROUND: Impairment in social functioning is a key component of personality
      disorder. Therefore psycho-education and problem solving (PEPS) therapy may
      benefit people with this disorder. Psycho-education aims to educate, build
      rapport, and motivate people for problem solving therapy. Problem solving therapy
      aims to help clients solve interpersonal problems positively and rationally,
      thereby improving social functioning and reducing distress. PEPS therapy has been
      evaluated with community adults with personality disorder in an exploratory
      trial. At the end of treatment, compared to a wait-list control group, those
      treated with PEPS therapy showed better social functioning, as measured by the
      Social Functioning Questionnaire (SFQ). A definitive evaluation is now being
      conducted to determine whether PEPS therapy is a clinically and cost-effective
      treatment for people with personality disorder METHODS: This is a pragmatic, two
      arm, multi-centre, parallel, randomised controlled clinical trial. The target
      population is community-dwelling adults with one or more personality disorder, as
      identified by the International Personality Disorder Examination (IPDE).
      Inclusion criteria are: Living in the community (including residential or
      supported care settings); presence of one or more personality disorder; aged 18
      or over; proficiency in spoken English; capacity to provide informed consent.
      Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient
      degree of literacy, comprehension or attention to be able to engage in trial
      therapy and assessments; currently engaged in a specific programme of
      psychological treatment for personality disorder or likely to start such
      treatment during the trial period; currently enrolled in any other trial.
      Suitable participants are randomly allocated to PEPS therapy plus treatment as
      usual (TAU) or TAU only. We aim to recruit 340 men and women. The primary outcome
      is social functioning as measured by the SFQ. A reduction (i.e., an improvement)
      of 2 points or more on the SFQ at follow-up 72 weeks post-randomisation is our
      pre-specified index of clinically significant change. Secondary outcomes include
      a reduction of unscheduled service usage and an increase in scheduled service
      usage; improved quality of life; and a reduction in mental distress. DISCUSSION:
      PEPS therapy has potential as an economical, accessible, and acceptable
      intervention for people with personality disorder. The results from this
      randomised controlled trial will tell us if PEPS therapy is effective and cost
      effective. If so, then it will be a useful treatment for inclusion in a broader
      menu of treatment options for this group of service users. TRIAL REGISTRATION:
      International Standard Randomised Controlled Trial Number - ISRCTN70660936.

PMID- 21864371
TI  - Recurrent takotsubo cardiomyopathy in the setting of transient neurological
      symptoms: a case report.
AB  - INTRODUCTION: First described in Japan, takotsubo cardiomyopathy is increasingly
      becoming recognized worldwide as a cause of sudden and reversible diminished left
      ventricular function characterized by left apical ballooning and hyperkinesis of
      the basal segments, often with symptoms mimicking a myocardial infarction.
      Associated with physical or emotional stress, its exact pathogenesis has not been
      established, though evidence supports a neurohumoral etiology. Additionally,
      recurrence of this condition is rare. In this report, we present a rare case of
      recurrent takotsubo cardiomyopathy in a post-menopausal woman who presented with
      transient neurological complaints on both occasions. CASE PRESENTATION: We
      present a rare case of a 76-year-old Caucasian woman with no history of
      congestive heart failure who presented to our emergency department twice with
      transient neurological complaints. On the first occasion, she was found to have
      transient aphasia which resolved within 24 hours, yet during that period she also
      developed symptoms of congestive heart failure and was noted to have a new,
      significantly depressed ejection fraction with apical akinesis and possible
      apical thrombus. One month after her presentation a repeat echocardiogram
      revealed complete resolution of all wall motion abnormalities and a return to
      baseline status. Seven months later she presented with ataxia, was diagnosed with
      vertebrobasilar insufficiency, and again developed symptoms and echocardiography
      findings similar to those of her first presentation. Once again, at her one-month
      follow-up examination, all wall motion abnormalities had completely resolved and
      her ejection fraction had returned to normal. CONCLUSION: Though the exact
      etiology of takotsubo cardiomyopathy is unclear, a neurohumoral mechanism has
      been proposed. Recurrence of this disorder is rare, though it has been reported
      in patients with structural brain abnormalities. This report is the first to
      describe recurrent takotsubo cardiomyopathy in a patient with transient
      neurological symptoms. In our patient, as expected in patients with this
      condition, complete resolution of all left ventricular abnormalities occurred
      within a short period of time. It is important for clinicians to be aware of this
      increasingly recognized syndrome, including its association with recurrence,
      especially in the clinical setting of neurologic dysfunction.

PMID- 21864372
TI  - T cell subpopulations in lymph nodes may not be predictive of patient outcome in
      colorectal cancer.
AB  - BACKGROUND: The immune response has been proposed to be an important factor in
      determining patient outcome in colorectal cancer (CRC). Previous studies have
      concentrated on characterizing T cell populations in the primary tumour where T
      cells with regulatory effect (Foxp3+ Tregs) have been identified as both
      enhancing and diminishing anti-tumour immune responses. No previous studies have
      characterized the T cell response in the regional lymph nodes in CRC. METHODS:
      Immunohistochemistry was used to analyse CD4, CD8 or Foxp3+ T cell populations in
      the regional lymph nodes of patients with stage II CRC (n = 31), with (n = 13) or
      without (n = 18) cancer recurrence after 5 years of follow up, to determine if
      the priming environment for anti-tumour immunity was associated with clinical
      outcome. RESULTS: The proportions of CD4, CD8 or Foxp3+ cells in the lymph nodes
      varied widely between and within patients, and there was no association between T
      cell populations and cancer recurrence or other clinicopathological
      characteristics. CONCLUSIONS: These data indicate that frequency of these T cell
      subsets in lymph nodes may not be a useful tool for predicting patient outcome.

PMID- 21864373
TI  - Gait training with partial body weight support during overground walking for
      individuals with chronic stroke: a pilot study.
AB  - BACKGROUND: It is not yet established if the use of body weight support (BWS)
      systems for gait training is effective per se or if it is the combination of BWS
      and treadmill that improves the locomotion of individuals with gait impairment.
      This study investigated the effects of gait training on ground level with partial
      BWS in individuals with stroke during overground walking with no BWS. METHODS:
      Twelve individuals with chronic stroke (53.17 +/- 7.52 years old) participated of
      a gait training program with BWS during overground walking, and were evaluated
      before and after the gait training period. In both evaluations, individuals were
      videotaped walking at a self-selected comfortable speed with no BWS. Measurements
      were obtained for mean walking speed, step length, stride length and speed, toe
      clearance, durations of total double stance and single-limb support, and minimum
      and maximum foot, shank, thigh, and trunk segmental angles. RESULTS: After gait
      training, individuals walked faster, with symmetrical steps, longer and faster
      strides, and increased toe-clearance. Also, they displayed increased rotation of
      foot, shank, thigh, and trunk segmental angles on both sides of the body.
      However, the duration of single-limb support remained asymmetrical between each
      side of the body after gait training. CONCLUSIONS: Gait training individuals with
      chronic stroke with BWS during overground walking improved walking in terms of
      temporal-spatial parameters and segmental angles. This training strategy might be
      adopted as a safe, specific and promising strategy for gait rehabilitation after
      stroke.

PMID- 21864374
TI  - Chest pain with ST segment elevation in a patient with prosthetic aortic valve
      infective endocarditis: a case report.
AB  - INTRODUCTION: Acute ST-segment elevation myocardial infarction secondary to
      atherosclerotic plaque rupture is a common medical emergency. This condition is
      effectively managed with percutaneous coronary intervention or thrombolysis. We
      report a rare case of acute myocardial infarction secondary to coronary
      embolisation of valvular vegetation in a patient with infective endocarditis, and
      we highlight how the management of this phenomenon may not be the same. CASE
      PRESENTATION: A 73-year-old British Caucasian man with previous tissue aortic
      valve replacement was diagnosed with and treated for infective endocarditis of
      his native mitral valve. His condition deteriorated in hospital and repeat
      echocardiography revealed migration of vegetation to his aortic valve. Whilst
      waiting for surgery, our patient developed severe central crushing chest pain
      with associated anterior ST segment elevation on his electrocardiogram. Our
      patient had no history or risk factors for ischaemic heart disease. It was likely
      that coronary embolisation of part of the vegetation had occurred. Thrombolysis
      or percutaneous coronary intervention treatments were not performed in this
      setting and a plan was made for urgent surgical intervention. However, our
      patient deteriorated rapidly and unfortunately died. CONCLUSION: Clinicians need
      to be aware that atherosclerotic plaque rupture is not the only cause of acute
      myocardial infarction. In the case of septic vegetation embolisation, case report
      evidence reveals that adopting the current strategies used in the treatment of
      myocardial infarction can be dangerous. Thrombolysis risks intra-cerebral
      hemorrhage from mycotic aneurysm rupture. Percutaneous coronary intervention
      risks coronary mycotic aneurysm formation, stent infections as well as distal
      septic embolisation. As yet, there remains no defined treatment modality and we
      feel all cases should be referred to specialist cardiac centers to consider how
      best to proceed.

PMID- 21864375
TI  - Development of ELISA-based methods to measure the anti-malarial drug chloroquine
      in plasma and in pharmaceutical formulations.
AB  - BACKGROUND: In Central and South America and Eastern and Southern Africa,
      Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases,
      respectively. In these areas, chloroquine (CQ) remains the treatment of choice
      for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV
      1 therapeutic agent. There is a dire need to continue monitoring quality of CQ as
      there is a major influx of substandard and fake formulations into malaria-endemic
      countries. The use of fake/substandard drugs will result in sub-therapeutic
      levels endangering the patient and possibly select for parasite resistance. The
      aim of this study was to develop an inexpensive, simple antibody-based ELISA to
      measure CQ concentrations in tablets and in plasma. METHODS: A monoclonal
      antibody (MAb) that reacts with the N-side chain of the CQ molecule was prepared
      by use of a CQ analogue. A specific and reliable ELISA for detection of CQ was
      developed. The developed assay was validated by measuring CQ in tablets sold in
      Denmark, India and Sudan. Furthermore, kinetics of CQ concentrations in plasma of
      four volunteers, who ingested two tablets of Malarex(r) containing, 250 mg CQ
      base, were measured before drug intake, three hours later and thereafter at days
      1, 3, 7, 14, 21 and 28. The same plasma samples were simultaneously measured by
      high performance liquid chromatography (HPLC). RESULTS: The ELISA proved an easy
      to-handle and very sensitive tool for the detection of CQ with a lower limit of
      detection at 3.9 ng/ml. ELISA levels of CQ in plasma showed high agreement with
      the levels obtained by HPLC (r = 0.98). The specificity in the negative control
      group was 100%. CONCLUSION: The developed ELISA can be used for quality screening
      of CQ in pharmaceutical formulations and for drug monitoring in malaria and in
      other infectious diseases, such as HIV, where CQ proved to be an effective
      therapeutic agent. The methodology has been exploited to develop monoclonal
      antibodies for the drugs used in artemisinin-based combination therapy (ACT).

PMID- 21864378
TI  - Inflammatory myopathy and severe rhabdomyolysis induced by leuprolide acetate
      therapy for prostate cancer: a case report.
AB  - INTRODUCTION: Leuprolide acetate is a synthetic analog of gonadotropin-releasing
      hormone used for the treatment of prostate cancer. Its side effects are hot
      flashes, nausea, and fatigue. We report a case of a patient with proximal
      inflammatory myopathy accompanied by severe rhabdomyolysis and renal failure
      following the second application of leuprolide acetate. Drug withdrawal and
      steroid therapy resulted in remission within six weeks of the diagnosis. To the
      best of our knowledge, our case report describes the second case of leuprolide
      acetate-induced inflammatory myopathy and the first case of severe leuprolide
      acetate-induced rhabdomyolysis and renal failure in the literature. CASE
      PRESENTATION: A 64-year-old Swiss Caucasian man was admitted to the hospital
      because of progressive proximal muscle weakness, dyspnea, and oliguria. He had
      been treated twice with leuprolide acetate in monthly doses. We performed a
      muscle biopsy, which excluded other causes of myopathy. The patient's renal
      failure and rhabdomyolysis were treated with rehydration and steroid therapy.
      CONCLUSION: The aim of our case report is to highlight the rare but severe side
      effects associated with leuprolide acetate therapy used to treat patients with
      inflammatory myopathy: severe rhabdomyolysis and renal failure.

PMID- 21864376
TI  - Tribbles homolog 3 denotes a poor prognosis in breast cancer and is involved in
      hypoxia response.
AB  - INTRODUCTION: Hypoxia in solid tumors is associated with treatment resistance,
      resulting in poor prognosis. Tribbles homolog 3 (TRIB3) is induced during hypoxia
      and is involved in multiple cellular pathways involved in cell survival. Here, we
      investigated the role of TRIB3 in breast cancer. METHODS: TRIB3 mRNA expression
      was measured in breast tumor tissue from 247 patients and correlated with
      clinicopathological parameters and clinical outcome. Furthermore, we studied
      TRIB3 expression regulation in cell lines, xenografts tissues and human breast
      cancer material using Reverse transcriptase, quantitative polymerase chain
      reaction (RT-qPCR) and immunohistochemical staining. Finally, the effect of small
      interfering RNA (siRNA) mediated TRIB3 knockdown on hypoxia tolerance was
      assessed. RESULTS: Breast cancer patients with low, intermediate or high TRIB3
      expression exhibited a mean disease free survival (DFS) of 80 (95% confidence
      interval [CI] = 74 to 86), 74 (CI = 67 to 81), and 63 (CI = 55 to 71) months
      respectively (P = .002, Mantel-Cox log-rank). The prognostic value of TRIB3 was
      limited to those patients that had received radiotherapy as part of their primary
      treatment (n = 179, P = .005) and remained statistically significant after
      correction for other clinicopathological parameters (DFS, Hazard Ratio = 1.90, CI
      = 1.17 to 3.08, P = .009). In breast cell lines TRIB3 expression was induced by
      hypoxia, nutrient starvation, and endoplasmic reticulum stress in an hypoxia
      inducible factor 1 (HIF-1) independent manner. TRIB3 induction after hypoxia did
      not increase with decreasing oxygen levels. In breast tumor xenografts and human
      breast cancer tissues TRIB3 co-localized with the hypoxic cell marker
      pimonidazole. The induction of TRIB3 by hypoxia was shown to be regulated via the
      PERK/ATF4/CHOP pathway of the unfolded protein response and knockdown of TRIB3
      resulted in a dose-dependent increase in hypoxia sensitivity. CONCLUSIONS: TRIB3
      is independently associated with poor prognosis of breast cancer patients,
      possibly through its association with tumor cell hypoxia.

PMID- 21864377
TI  - Profile of small interfering RNAs from cotton plants infected with the
      polerovirus Cotton leafroll dwarf virus.
AB  - BACKGROUND: In response to infection, viral genomes are processed by Dicer-like
      (DCL) ribonuclease proteins into viral small RNAs (vsRNAs) of discrete sizes.
      vsRNAs are then used as guides for silencing the viral genome. The profile of
      vsRNAs produced during the infection process has been extensively studied for
      some groups of viruses. However, nothing is known about the vsRNAs produced
      during infections of members of the economically important family Luteoviridae, a
      group of phloem-restricted viruses. Here, we report the characterization of a
      population of vsRNAs from cotton plants infected with Cotton leafroll dwarf virus
      (CLRDV), a member of the genus Polerovirus, family Luteoviridae. RESULTS: Deep
      sequencing of small RNAs (sRNAs) from leaves of CLRDV-infected cotton plants
      revealed that the vsRNAs were 21- to 24-nucleotides (nt) long and that their
      sequences matched the viral genome, with higher frequencies of matches in the 3-
      region. There were equivalent amounts of sense and antisense vsRNAs, and the 22
      nt class of small RNAs was predominant. During infection, cotton Dcl transcripts
      appeared to be up-regulated, while Dcl2 appeared to be down-regulated.
      CONCLUSIONS: This is the first report on the profile of sRNAs in a plant infected
      with a virus from the family Luteoviridae. Our sequence data strongly suggest
      that virus-derived double-stranded RNA functions as one of the main precursors of
      vsRNAs. Judging by the profiled size classes, all cotton DCLs might be working to
      silence the virus. The possible causes for the unexpectedly high accumulation of
      22-nt vsRNAs are discussed. CLRDV is the causal agent of Cotton blue disease,
      which occurs worldwide. Our results are an important contribution for
      understanding the molecular mechanisms involved in this and related diseases.

PMID- 21864379
TI  - Molecular markers of antifolate resistance in Plasmodium falciparum isolates from
      Luanda, Angola.
AB  - BACKGROUND: Plasmodium falciparum malaria remains a leading health problem in
      Africa and its control is seriously challenged by drug resistance. Although
      resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination
      remains an important component of malaria control programmes as intermittent
      preventive therapy (IPT) for pregnant women and children. In Angola, resistance
      patterns have been poorly characterized, and IPT has been employed for pregnant
      women since 2006. The aim of this study was to assess the prevalence of key
      antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in
      P. falciparum samples from Angola. METHODS: Plasmodium falciparum samples
      collected in Luanda, in 2007, were genotyped by amplification and DNA forward and
      reverse sequencing of the pfdhfr and pfdhps genes. RESULTS: The most prevalent
      polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps
      437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed
      in West Africa were also identified (540E in 10%, 581G in 7% of samples).
      CONCLUSION: This study documents an important prevalence of 4 P. falciparum
      polymorphisms that predicts an antifolate resistance in Luanda. Further, some
      samples presented additional mutations associated to high-level resistance. These
      results suggest that the use of SP for IPT may no longer be warranted in Angola.

PMID- 21864380
TI  - Diagnostic accuracy of procalcitonin in critically ill immunocompromised
      patients.
AB  - BACKGROUND: Recognizing infection is crucial in immunocompromised patients with
      organ dysfunction. Our objective was to assess the diagnostic accuracy of
      procalcitonin (PCT) in critically ill immunocompromised patients. METHODS: This
      prospective, observational study included patients with suspected sepsis.
      Patients were classified into one of three diagnostic groups: no infection,
      bacterial sepsis, and nonbacterial sepsis. RESULTS: We included 119 patients with
      a median age of 54 years (interquartile range [IQR], 42-68 years). The general
      severity (SAPSII) and organ dysfunction (LOD) scores on day 1 were 45 (35-62.7)
      and 4 (2-6), respectively, and overall hospital mortality was 32.8%. Causes of
      immunodepression were hematological disorders (64 patients, 53.8%), HIV infection
      (31 patients, 26%), and solid cancers (26 patients, 21.8%). Bacterial sepsis was
      diagnosed in 58 patients and nonbacterial infections in nine patients (7.6%); 52
      patients (43.7%) had no infection. PCT concentrations on the first ICU day were
      higher in the group with bacterial sepsis (4.42 [1.60-22.14] vs. 0.26 [0.09-1.26]
      ng/ml in patients without bacterial infection, P < 0.0001). PCT concentrations on
      day 1 that were > 0.5 ng/ml had 100% sensitivity but only 63% specificity for
      diagnosing bacterial sepsis. The area under the receiver operating characteristic
      (ROC) curve was 0.851 (0.78-0.92). In multivariate analyses, PCT concentrations >
      0.5 ng/ml on day 1 independently predicted bacterial sepsis (odds ratio, 8.6; 95%
      confidence interval, 2.53-29.3; P = 0.0006). PCT concentrations were not
      significantly correlated with hospital mortality. CONCLUSION: Despite limited
      specificity in critically ill immunocompromised patients, PCT concentrations may
      help to rule out bacterial infection.

PMID- 21864381
TI  - Subgroups of older adults with osteoarthritis based upon differing comorbid
      symptom presentations and potential underlying pain mechanisms.
AB  - INTRODUCTION: Although people with knee and hip osteoarthritis (OA) seek
      treatment because of pain, many of these individuals have commonly co-occurring
      symptoms (for example, fatigue, sleep problems, mood disorders). The purpose of
      this study was to characterize adults with OA by identifying subgroups with the
      above comorbid symptoms along with illness burden (a composite measure of somatic
      symptoms) to begin to examine whether subsets may have differing underlying pain
      mechanisms. METHODS: Community-living older adults with symptomatic knee and hip
      OA (n = 129) participated (68% with knee OA, 38% with hip OA). Hierarchical
      agglomerative cluster analysis was used. To determine the relative contribution
      of each variable in a cluster, multivariate analysis of variance was used.
      RESULTS: We found three clusters. Cluster 1 (n = 45) had high levels of pain,
      fatigue, sleep problems, and mood disturbances. Cluster 2 (n = 38) had
      intermediate degrees of depression and fatigue, but low pain and good sleep.
      Cluster 3 (n = 42) had the lowest levels of pain, fatigue, and depression, but
      worse sleep quality than Cluster 2. CONCLUSIONS: In adults with symptomatic OA,
      three distinct subgroups were identified. Although replication is needed, many
      individuals with OA had symptoms other than joint pain and some (such as those in
      Cluster 1) may have relatively stronger central nervous system (CNS)
      contributions to their symptoms. For such individuals, therapies may need to
      include centrally-acting components in addition to traditional peripheral
      approaches.

PMID- 21864382
TI  - Deep sequencing reveals as-yet-undiscovered small RNAs in Escherichia coli.
AB  - BACKGROUND: In Escherichia coli, approximately 100 regulatory small RNAs (sRNAs)
      have been identified experimentally and many more have been predicted by various
      methods. To provide a comprehensive overview of sRNAs, we analysed the low
      molecular-weight RNAs (< 200 nt) of E. coli with deep sequencing, because the
      regulatory RNAs in bacteria are usually 50-200 nt in length. RESULTS: We
      discovered 229 novel candidate sRNAs (>= 50 nt) with computational or
      experimental evidence of transcription initiation. Among them, the expression of
      seven intergenic sRNAs and three cis-antisense sRNAs was detected by northern
      blot analysis. Interestingly, five novel sRNAs are expressed from prophage
      regions and we note that these sRNAs have several specific characteristics.
      Furthermore, we conducted an evolutionary conservation analysis of the candidate
      sRNAs and summarised the data among closely related bacterial strains.
      CONCLUSIONS: This comprehensive screen for E. coli sRNAs using a deep sequencing
      approach has shown that many as-yet-undiscovered sRNAs are potentially encoded in
      the E. coli genome. We constructed the Escherichia coli Small RNA Browser
      (ECSBrowser; http://rna.iab.keio.ac.jp/), which integrates the data for
      previously identified sRNAs and the novel sRNAs found in this study.

PMID- 21864383
TI  - Functional categorization of unique expressed sequence tags obtained from the
      yeast-like growth phase of the elm pathogen Ophiostoma novo-ulmi.
AB  - BACKGROUND: The highly aggressive pathogenic fungus Ophiostoma novo-ulmi
      continues to be a serious threat to the American elm (Ulmus americana) in North
      America. Extensive studies have been conducted in North America to understand the
      mechanisms of virulence of this introduced pathogen and its evolving population
      structure, with a view to identifying potential strategies for the control of
      Dutch elm disease. As part of a larger study to examine the genomes of
      economically important Ophiostoma spp. and the genetic basis of virulence, we
      have constructed an expressed sequence tag (EST) library using total RNA
      extracted from the yeast-like growth phase of O. novo-ulmi (isolate H327).
      RESULTS: A total of 4,386 readable EST sequences were annotated by determining
      their closest matches to known or theoretical sequences in public databases by
      BLASTX analysis. Searches matched 2,093 sequences to entries found in Genbank,
      including 1,761 matches with known proteins and 332 matches with unknown
      (hypothetical/predicted) proteins. Known proteins included a collection of 880
      unique transcripts which were categorized to obtain a functional profile of the
      transcriptome and to evaluate physiological function. These assignments yielded
      20 primary functional categories (FunCat), the largest including Metabolism
      (FunCat 01, 20.28% of total), Sub-cellular localization (70, 10.23%), Protein
      synthesis (12, 10.14%), Transcription (11, 8.27%), Biogenesis of cellular
      components (42, 8.15%), Cellular transport, facilitation and routes (20, 6.08%),
      Classification unresolved (98, 5.80%), Cell rescue, defence and virulence (32,
      5.31%) and the unclassified category, or known sequences of unknown metabolic
      function (99, 7.5%). A list of specific transcripts of interest was compiled to
      initiate an evaluation of their impact upon strain virulence in subsequent
      studies. CONCLUSIONS: This is the first large-scale study of the O. novo-ulmi
      transcriptome. The expression profile obtained from the yeast-like growth phase
      of this species will facilitate a multigenic approach to gene expression studies
      to assess their role in the determination of pathogenicity for this species. The
      identification and evaluation of gene targets in such studies will be a
      prerequisite to the development of biological control strategies for this
      pathogen.

PMID- 21864384
TI  - Application of DNA-based diagnostics in detection of schistosomal DNA in early
      infection and after drug treatment.
AB  - BACKGROUND: Research is now focused on identification of sensitive and specific
      diagnostic tests for early identification of schistosomal infection and
      evaluation of chemotherapy in field situations in China. RESULTS: This study
      compared loop-mediated isothermal amplification (LAMP) with conventional PCR as
      DNA-based diagnostic techniques for the early detection of schistosomal DNA and
      the evaluation of chemotherapy. The results showed that both PCR and LAMP assays
      targeting a 301 base pair (bp) sequence of the highly repetitive retrotransposon,
      SjR2, amplified DNA from schistosomes but were unable to distinguish between
      schistosome species. LAMP and conventional PCR were shown to amplify the target
      sequence of the SjR2-pCR2.1 recombinant plasmid template with limits of detection
      of 10-4 ng and 10-2 ng, respectively, thus demonstrating the superior sensitivity
      of the LAMP method. Schistosoma japonicum DNA was detected in all serum samples
      obtained from the three experimental groups at 1 week post-infection by LAMP
      assay, while the rate of detection by conventional PCR ranged from 50% to 66%.
      The potential application of PCR and LAMP assays for the evaluation of artesunate
      and praziquantel chemotherapy was investigated. PCR was shown to be less
      sensitive for detection of schistosomal DNA in drug-treated rabbit sera than the
      LAMP method. CONCLUSIONS: The data presented here indicate that LAMP is suitable
      for the detection of early infection in the groups primarily infected with
      Schistosoma japonicum, such as migrants, travellers, military personnel and the
      younger age groups. However, it is less suitable for evaluation of the efficacy
      of chemotherapy in the early stages because of its high sensitivity.

PMID- 21864385
TI  - Cystic appearance of low-grade endometrial stromal sarcoma in the right atrium:
      case report.
AB  - A 71-year-old woman presented with a right adnexal solid mass invading the right
      gonadal vein and inferior vena cava up to the hepatic veins revealed by CT and
      confirmed by MRI. A thin-walled cyst and a solid mass were unexpectedly found in
      the right atrium by transesophageal echocardiography (TEE) in the operating room.
      Using color Doppler and air bubbles as contrast material a circumscribed cyst was
      confirmed and localized close to the IVC. The cyst was connected to the mass in
      the inferior vena cava. The tumor, including the cyst, was removed without using
      cardiopulmonary bypass and described as a low-grade endometrial stromal sarcoma,
      a rare slowly growing tumor. This is the first TEE description of endometrial
      stromal sarcoma manifesting as a right atrial cyst.

PMID- 21864386
TI  - Effects of radiation therapy on tissue and serum concentrations of tumour
      associated trypsin inhibitor and their prognostic significance in rectal cancer
      patients.
AB  - BACKGROUND: We have previously demonstrated that elevated concentrations of
      tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in
      serum (s-TATI) are associated with a poor prognosis in colorectal cancer
      patients. It was also found that s-TATI concentrations were lower in patients
      with rectal cancer compared to patients with colon cancer. In this study, we
      investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t
      TATI and s-TATI in patients with rectal cancer. METHODS: TATI was analysed in
      serum, normal mucosa and tumour tissue collected at various time points in 53
      rectal cancer patients enrolled in a case-control study where 12 patients
      received surgery alone, 20 patients 5 * 5 Gy (short-term) preoperative RT and 21
      patients 25 * 2 Gy (long-term) preoperative RT. T-TATI was analysed by
      immunohistochemistry and s-TATI was determined by an immunofluorometric assay.
      Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI
      concentrations in relation to RT. Spearman's correlation (R) test was used to
      explore the associations between t-TATI, s-TATI and clinicopathological
      parameters. Overall survival (OS) according to high and low t-TATI and s-TATI
      concentrations was estimated by classification and regression tree analysis,
      Kaplan-Meier analysis and the log rank test. RESULTS: RT did not affect
      concentrations of t-TATI or s-TATI. In patients receiving short-term but not long
      term RT, s-TATI concentrations were significantly higher 4 weeks post surgery
      than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression
      correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in
      surgical specimens was associated with a significantly shorter OS (P = 0.045). S
      TATI concentrations in serum drawn at all time points were associated with an
      impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post
      surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021)
      and with increased s-creatinine concentrations assessed prior to surgery (P =
      0.041). CONCLUSIONS: The results presented here further validate the utility of t
      TATI and s-TATI as prognostic biomarkers in patients with rectal cancer,
      independent of neoadjuvant RT.

PMID- 21864387
TI  - Lighting and perceptual cues: effects on gait measures of older adults at high
      and low risk for falls.
AB  - BACKGROUND: The visual system plays an important role in maintaining balance. As
      a person ages, gait becomes slower and stride becomes shorter, especially in
      dimly lighted environments. Falls risk has been associated with reduced speed and
      increased gait variability. METHODS: Twenty-four older adults (half identified at
      risk for falls) experienced three lighting conditions: pathway illuminated by 1)
      general ceiling-mounted fixtures, 2) conventional plug-in night lights and 3)
      plug-in night lights supplemented by laser lines outlining the pathway. Gait
      measures were collected using the GAITRite(c) walkway system. RESULTS:
      Participants performed best under the general ceiling-mounted light system and
      worst under the night light alone. The pathway plus night lights increased gait
      velocity and reduced step length variability compared to the night lights alone
      in those at greater risk of falling. CONCLUSIONS: Practically, when navigating in
      more challenging environments, such as in low-level ambient illumination, the
      addition of perceptual cues that define the horizontal walking plane can
      potentially reduce falls risks in older adults.

PMID- 21864388
TI  - Lack of association between gene polymorphisms of Angiotensin converting enzyme,
      Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of
      Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in
      Caucasians.
AB  - BACKGROUND: Several polymorphisms of genes involved in the immunological
      recognition of Helicobacter pylori and regulating apoptosis and proliferation
      have been linked to gastric carcinogenesis, however reported data are partially
      conflicting. The aim of our study was to evaluate potential associations between
      the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and
      polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like
      receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. METHODS: Gene
      polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222,
      controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A
      (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G
      (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches
      and restriction fragment length polymorphism analysis. RESULTS: Frequencies of
      genotypes in our study are similar to the data reported on subjects of Caucasian
      ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with
      increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G
      genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2%
      respectively, however it failed to reach significance level (p = 0.077). We did
      not find any significant associations for all polymorphisms in relation to GC or
      HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated
      with Helicobacter pylori infection. CONCLUSIONS: ACE, NOD1, TRL4 and FAS/FASL
      gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and
      therefore they should not be considered as potential biomarkers for identifying
      individuals with higher risk for GC.

PMID- 21864389
TI  - Prevalence of chronic kidney disease among people living with HIV/AIDS in
      Burundi: a cross-sectional study.
AB  - BACKGROUND: Since little is known about chronic kidney disease (CKD) among people
      living with HIV/AIDS (PLWHA) in Sub-Saharan Africa, the prevalence and nature of
      CKD were assessed in Burundi through a multicenter cross-sectional study.
      METHODS: Patients underwent assessments at baseline and 3 months later.
      Glomerular Filtration Rate (GFR) was estimated using abbreviated 4-variable
      Modification of Diet in Renal Diseases (MDRD) and Cockroft-Gault estimation
      methods. Patients were classified at month 3 into various CKD stages using the
      National Kidney Foundation (NKF) definition, which combines GFR and urinary
      abnormalities. Risk factors for presence of proteinuria (PRO) and aseptic
      leukocyturia (LEU) were further analyzed using multiple logistic regression.
      RESULTS: Median age of the patients in the study (N = 300) was 40 years, 70.3%
      were female and 71.7% were on highly active antiretroviral therapy. Using the
      MDRD method, CKD prevalence in patients was 45.7%, 30.2% of whom being classified
      as stage 1 according to the NKF classification, 13.5% as stage 2 and 2% as stage
      3. No patient was classified as stage 4 or 5. Among CKD patients with urinary
      abnormality, PRO accounted for 6.1% and LEU for 18.4%. Significant associations
      were found between LEU and non-steroidal anti-inflammatory drug (NSAID) use,
      previous history of tuberculosis, low body mass index and female gender and
      between PRO and high viral load. CONCLUSION: Our study, using a very sensitive
      definition for CKD evaluation, suggests a potentially high prevalence of CKD
      among PLWHA in Burundi. Patients should be regularly monitored and preventative
      measures implemented, such as monitoring NSAID use and adjustment of drug dosages
      according to body weight. Urine dipsticks could be used as a screening tool to
      detect patients at risk of renal impairment.

PMID- 21864390
TI  - Acute nerve stretch and the compound motor action potential.
AB  - In this paper, the acute changes in the compound motor action potential (CMAP)
      during mechanical stretch were studied in hamster sciatic nerve and compared to
      the changes that occur during compression.In response to stretch, the nerve
      physically broke when a mean force of 331 gm (3.3 N) was applied while the CMAP
      disappeared at an average stretch force of 73 gm (0.73 N). There were 5 primary
      measures of the CMAP used to describe the changes during the experiment: the
      normalized peak to peak amplitude, the normalized area under the curve (AUC), the
      normalized duration, the normalized velocity and the normalized velocity
      corrected for the additional path length the impulses travel when the nerve is
      stretched. Each of these measures was shown to contain information not available
      in the others.During stretch, the earliest change is a reduction in conduction
      velocity followed at higher stretch forces by declines in the amplitude of the
      CMAP. This is associated with the appearance of spontaneous EMG activity. With
      stretch forces < 40 gm (0.40 N), there is evidence of increased excitability
      since the corrected velocities increase above baseline values. In addition, there
      is a remarkable increase in the peak to peak amplitude of the CMAP after recovery
      from stretch < 40 gm, often to 20% above baseline.Multiple means of predicting
      when a change in the CMAP suggests a significant stretch are discussed and it is
      clear that a multifactorial approach using both velocity and amplitude parameters
      is important. In the case of pure compression, it is only the amplitude of the
      CMAP that is critical in predicting which changes in the CMAP are associated with
      significant compression.

PMID- 21864391
TI  - Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1
      virus infection: an observational cohort study.
AB  - BACKGROUND: There was a pandemic influenza around the world in 2009 including
      South Korea since last pandemic occurred four decades ago. We aimed to evaluate
      the epidemiological and clinical characteristics of this infection in childhood.
      METHODS: We evaluated the epidemiologic characteristics of all the subjects
      infected with the 2009 H1N1 influenza A virus (2,971 patients, <= 15 years of
      age), and the clinical and laboratory findings of the inpatients (217 patients,
      80 had pneumonia) between 1 September 2009 and 31 January 2010 in a single
      hospital throughout the epidemic. RESULTS: The age distribution of all the
      subjects was relatively even. Over 90% of cases occurred during a two-month
      period. Two hundred and five patients (94.5%) received oseltamivir within 48 h of
      fever onset, and 97% of inpatients defervesced within 48 h of medication. The
      group with pneumonia included more males than females, and had higher leukocytes
      counts with lower lymphocyte differentials than the group without pneumonia. The
      white blood cell count and lymphocyte differential were associated with the
      severity of pneumonia. Corticosteroid treatment for severe pneumonia patients was
      highly effective in preventing disease progression. CONCLUSION: Children of all
      ages affected with even rates of infection, but males were predominant in
      pneumonia patients. Pneumonia patients showed lymphopenia and its severity was
      associated with the severity of illness. Our results suggest that the mechanism
      of lung injury in 2009 H1N1 virus infection may be associated with the host
      immune response.

PMID- 21864392
TI  - Simultaneous use of traditional Chinese medicine (si-ni-tang) to treat septic
      shock patients: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Even though there are continually upgraded recommendations for
      managing sepsis, such as "Surviving Sepsis Campaign: international guidelines for
      management of severe sepsis and septic shock", mortality is still high. Si-ni
      tang, a remedy documented in Shanghan Lun, a medical collection from ancient
      China, is used for treating patients with sepsis and septic shock. Using a well
      designed clinical trial, we are eager to survey the effectiveness of the
      concurrent use of this remedy in restoring these patients' hemodynamic status, or
      "Yang Qi". METHODS/DESIGN: Patients admitted to our medical intensive care units
      with the diagnosis of septic shock, defined as persistent hypotension induced by
      sepsis despite adequate fluid resuscitation, are eligible for participation. The
      inclusion criteria include: age from 20 to 85 years, conditions meeting the
      definition of septic shock, use of vasopressors within 24 hours of entering the
      study, and use of a nasogastric tube for feeding. The enrolled patients are
      randomly allocated either to the si-ni-tang group or the placebo group. The
      prescription of the trial drugs (si-ni-tang/placebo) is 2.25 grams 4 times a day
      for 7 days or till shock reversal (if shock reversal occurs in less than 7 days).
      Data, including duration of vasopressor infusion, gender, age, co-morbidities,
      APACHE II score, predicted mortality, ICU mortality, ICU length of stay, hospital
      mortality, hospital length of stay, source of sepsis, and culture results, are
      collected for the following analysis. DISCUSSION: Si-ni-tang is composed of
      processed Zingiber officinale, Glycyrrhiza uralensis, and Aconitum carmichaeli.
      Zingiber officinale and Glycyrrhiza uralensis are found to have the ability to
      reduce pro-inflammatory cytokine production, to inhibit lipopolisaccharide
      induced macrophage activation and function, and to lessen the bacterial load and
      suppress acute and chronic inflammation. Aconitum carmichaeli is known to have
      vasopressor activity, and positive chronotropic and inotropic effects. As this
      remedy has a potential benefit in treating septic shock patients, we designed a
      double-blind, prospective, randomized controlled trial and would like to publish
      the results and conclusions later. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01223430.

PMID- 21864393
TI  - Impact of the frequency of online verifications on the patient set-up accuracy
      and set-up margins.
AB  - PURPOSE: The purpose of the study was to evaluate the patient set-up error of
      different anatomical sites, to estimate the effect of different frequencies of
      online verifications on the patient set-up accuracy, and to calculate margins to
      accommodate for the patient set-up error (ICRU set-up margin, SM). METHODS AND
      MATERIALS: Alignment data of 148 patients treated with inversed planned intensity
      modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D
      CRT) of the head and neck (n = 31), chest (n = 72), abdomen (n = 15), and pelvis
      (n = 30) were evaluated. The patient set-up accuracy was assessed using
      orthogonal megavoltage electronic portal images of 2328 fractions of 173 planning
      target volumes (PTV). In 25 patients, two PTVs were analyzed where the PTVs were
      located in different anatomical sites and treated in two different radiotherapy
      courses. The patient set-up error and the corresponding SM were retrospectively
      determined assuming no online verification, online verification once a week and
      online verification every other day. RESULTS: The SM could be effectively reduced
      with increasing frequency of online verifications. However, a significant
      frequency of relevant set-up errors remained even after online verification every
      other day. For example, residual set-up errors larger than 5 mm were observed on
      average in 18% to 27% of all fractions of patients treated in the chest, abdomen
      and pelvis, and in 10% of fractions of patients treated in the head and neck
      after online verification every other day. CONCLUSION: In patients where high set
      up accuracy is desired, daily online verification is highly recommended.

PMID- 21864394
TI  - Combination of cyclosporine and erythropoietin improves brain infarct size and
      neurological function in rats after ischemic stroke.
AB  - BACKGROUND: This study tested the superiority of combined cyclosporine A (CsA)
      erythropoietin (EPO) therapy compared with either one in limiting brain
      infarction area (BIA) and preserving neurological function in rat after ischemic
      stroke (IS). METHODS: Fifty adult-male SD rats were equally divided into sham
      control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h
      after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group
      3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA
      and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after
      occlusion of distal left internal carotid artery. RESULTS: BIA on day 21 after
      acute IS was higher in group 2 than in other groups and lowest in group 5 (all p
      < 0.01). The sensorimotor functional test showed higher frequency of left turning
      in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and
      protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL
      were higher in group 2 than in other groups and lowest in group 1 and 5, whereas
      the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The
      expressions of inflammatory and oxidized protein were higher in group 2 than in
      other groups and lowest in group 1 and 5, whereas anti-inflammatory markers
      showed reversed changes in group 1 and other groups (all p < 0.05). The number of
      aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in
      group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01).
      CONCLUSION: combined treatment with CsA and EPO was superior to either one alone
      in protecting rat brain from ischemic damage after IS.

PMID- 21864396
TI  - Diabetes screening with hemoglobin A1c prior to a change in guideline
      recommendations: prevalence and patient characteristics.
AB  - BACKGROUND: In January 2010, the American Diabetes Association recommended the
      use of hemoglobin A1c (Hgb A1c) to screen and diagnose diabetes. This study
      explored the prevalence and clinical context of Hgb A1c tests done for non
      diabetic primary care patients for the three years prior to the release of the
      new guidelines. We sought to determine the provision of tests in non-diabetic
      patients age 19 or over, patients age 45 and over (eligible for routine diabetes
      screening), the annual change in the rate of this screening test, and the patient
      characteristics associated with the provision of Hgb A1c screening. METHODS: We
      conducted a retrospective study using data routinely collected in Electronic
      Medical Records. The participants were thirteen community-based family physicians
      in Toronto, Ontario. We calculated the proportion of non diabetic patients who
      had at least one Hbg A1c done in three years. We used logistic generalized
      estimating equation with year treated as a continuous variable to test for a non
      zero slope in yearly Hbg A1c provision. We modelled screening using multivariable
      logistic regression. RESULTS: There were 11,792 non-diabetic adults. Of these,
      1,678 (14.2%; 95%CI 13.6%-14.9%) had at least one Hgb A1c test done; this was
      higher for patients 45 years of age or older (20.2%; 95% CI 19.3% - 21.2%). The
      proportion of non-diabetic patients with an A1c test increased from 5.2% in 2007
      to 8.8% in 2009 (p < 0.0001 for presence of slope). Factors associated with
      significantly greater adjusted odds ratios of having the test done included
      increasing diastolic blood pressure, increasing fasting glucose, increasing body
      mass index, increasing age, as well as male gender and presence of hypertension,
      but not smoking status or LDL cholesterol. Patients living in the highest income
      quintile neighbourhoods had significantly lower odds ratios of having this test
      done than those in the lowest quintile (p < 0.001). CONCLUSIONS: A large and
      increasing proportion of the non-diabetic patients we studied have had an Hgb A1c
      for screening prior to guidelines recommending the test for this purpose. Several
      risk factors for cardiovascular disease or diabetes were associated with the
      provision of the Hgb A1c. Early uptake of the test may represent appropriate
      utilization.

PMID- 21864395
TI  - Exposure to arsenic in drinking water is associated with increased prevalence of
      diabetes: a cross-sectional study in the Zimapan and Lagunera regions in Mexico.
AB  - BACKGROUND: Human exposures to inorganic arsenic (iAs) have been linked to an
      increased risk of diabetes mellitus. Recent laboratory studies showed that
      methylated trivalent metabolites of iAs may play key roles in the diabetogenic
      effects of iAs. Our study examined associations between chronic exposure to iAs
      in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis
      endemic areas of Mexico. METHODS: We used fasting blood glucose (FBG), fasting
      plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin
      (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals.
      Arsenic levels in drinking water and urine were determined to estimate exposure
      to iAs. Urinary concentrations of iAs and its trivalent and pentavalent
      methylated metabolites were measured to assess iAs metabolism. Associations
      between diabetes and iAs exposure or urinary metabolites of iAs were estimated by
      logistic regression with adjustment for age, sex, hypertension and obesity.
      RESULTS: The prevalence of diabetes was positively associated with iAs in
      drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of
      dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05).
      Notably, FPI and HOMA-IR were negatively associated with iAs exposure (beta -2.08
      and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced
      diabetes differ from those underlying type-2 diabetes, which is typically
      characterized by insulin resistance. CONCLUSIONS: Our study confirms a previously
      reported, but frequently questioned, association between exposure to iAs and
      diabetes, and is the first to link the risk of diabetes to the production of one
      of the most toxic metabolites of iAs, DMAsIII.

PMID- 21864397
TI  - Factors determining the survival of nasopharyngeal carcinoma with lung metastasis
      alone: does combined modality treatment benefit?
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) with lung metastasis alone has been
      reported as a relatively favorable prognostic group, and combined modality
      treatment might be indicated for selected cases. However, the prognostic factors
      determining survival of this group and the indication of combined therapy have
      not been thoroughly studied. METHODS: We retrospectively reviewed 246 patients of
      NPC with lung metastasis(es) alone presented at diagnosis or as the first failure
      after primary treatment from 1993 to 2008 in an academic tertiary hospital.
      Univariate and multivariate survival analyses of post-metastasis survival (PMS)
      and overall survival (OS) were carried out to determine the prognostic factors.
      RESULTS: The 3-year, 5-year, and 10-year of PMS and OS for the whole cohort were
      34.3%, 17.0%, 8.6% and 67.8%, 45.4%, 18.5%, respectively. The median PMS (45.6
      months vs. 23.7 months) and OS (73.7 months vs. 46.2 months) of patients treated
      with combined therapy was significantly longer than that of those treated with
      chemotherapy alone (P < 0.001). Age, disease-free interval (DFI) and treatment
      modality were evaluated as independent prognostic factors of OS, while only age
      and treatment modality retain their independent significance in PMS analysis. In
      stratified survival analysis, compared to chemotherapy alone, combined therapy
      could benefit the patients with DFI > 1 year, but not those with DFI <= 1 year.
      CONCLUSIONS: Age <= 45 years, DFI > 1 year, and the combined therapy were good
      prognostic factors for NPC patients with lung metastasis(es) alone. The
      combination of local therapy and the basic chemotherapy should be considered for
      these patients with DFI > 1 year.

PMID- 21864398
TI  - Simultaneous utilization of glucose and xylose for lipid production by
      Trichosporon cutaneum.
AB  - BACKGROUND: Biochemical conversion of lignocellulose hydrolysates remains
      challenging, largely because most microbial processes have markedly reduced
      efficiency in the presence of both hexoses and pentoses. Thus, identification of
      microorganisms capable of efficient and simultaneous utilization of both glucose
      and xylose is pivotal to improving this process. RESULTS: In this study, we found
      that the oleaginous yeast strain Trichosporon cutaneum AS 2.571 assimilated
      glucose and xylose simultaneously, and accumulated intracellular lipid up to 59
      wt% with a lipid coefficient up to 0.17 g/g sugar, upon cultivation on a 2:1
      glucose/xylose mixture in a 3-liter stirred-tank bioreactor. In addition, no
      classic pattern of diauxic growth behavior was seen; the microbial cell mass
      increased during the whole culture process without any lag periods. In shake
      flask cultures with different initial glucose:xylose ratios, glucose and xylose
      were consumed simultaneously at rates roughly proportional to their individual
      concentrations in the medium, leading to complete utilization of both sugars at
      the same time. Simultaneous utilization of glucose and xylose was also seen
      during fermentation of corn-stover hydrolysate with a lipid content and
      coefficient of 39.2% and 0.15 g/g sugar, respectively. The lipid produced had a
      fatty-acid compositional profile similar to those of conventional vegetable oil,
      indicating that it could have potential as a raw material for biodiesel
      production. CONCLUSION: Efficient lipid production with simultaneous consumption
      of glucose and xylose was achieved in this study. This process provides an
      exciting opportunity to transform lignocellulosic materials into biofuel
      molecules, and should also encourage further study to elucidate this unique sugar
      assimilation mechanism.

PMID- 21864399
TI  - Acute medical unit comprehensive geriatric assessment intervention study
      (AMIGOS).
AB  - BACKGROUND: Many older people presenting to Acute Medical Units (AMU) are
      discharged after only a short stay (< 72 hours), yet many re-present to hospital
      or die within 1 year. Comprehensive Geriatric Assessment may improve patient
      outcomes for this group. METHOD:  PARTICIPANTS: Patients aged > 70 years and
      scoring positive on a risk screening tool ('Identification of Seniors At Risk')
      who are discharged within 72 hours of attending an AMU with a medical crisis,
      recruited prior to discharge. Sample size is 400. Carers of participants will
      also be recruited. INTERVENTION: Assessment on the AMU and further out-patient
      management by a specialist physician in geriatric medicine. Assessment and
      further management will follow the principles of Comprehensive Geriatric
      Assessment, providing advice and support to primary care services. DESIGN: Multi
      centre, individual patient randomised controlled trial comparing intervention
      with usual care. OUTCOME MEASUREMENT: Follow up is by postal questionnaire 90
      days after randomisation, and data will be entered into the study database by a
      researcher blind to allocation. The primary outcome is the number of days spent
      at home (for those admitted from home), or days spent in the same care home (if
      admitted from a care home). Secondary outcomes include mortality,
      institutionalisation, health and social care resource use, and scaled outcome
      measures, including quality of life, disability, mental well-being. Carer strain
      and well being will also be measured at 90 days. ANALYSES: Comparisons of
      outcomes and costs, and a cost utility analysis between the intervention and
      control groups will be carried out. TRIAL REGISTRATION: ISRCTN: ISRCTN21800480.

PMID- 21864400
TI  - Air pollution & the brain: Subchronic diesel exhaust exposure causes
      neuroinflammation and elevates early markers of neurodegenerative disease.
AB  - BACKGROUND: Increasing evidence links diverse forms of air pollution to
      neuroinflammation and neuropathology in both human and animal models, but the
      effects of long-term exposures are poorly understood. OBJECTIVE: We explored the
      central nervous system consequences of subchronic exposure to diesel exhaust (DE)
      and addressed the minimum levels necessary to elicit neuroinflammation and
      markers of early neuropathology. METHODS: Male Fischer 344 rats were exposed to
      DE (992, 311, 100, 35 and 0 MUg PM/m3) by inhalation over 6 months. RESULTS: DE
      exposure resulted in elevated levels of TNFalpha at high concentrations in all
      regions tested, with the exception of the cerebellum. The midbrain region was the
      most sensitive, where exposures as low as 100 MUg PM/m3 significantly increased
      brain TNFalpha levels. However, this sensitivity to DE was not conferred to all
      markers of neuroinflammation, as the midbrain showed no increase in IL-6
      expression at any concentration tested, an increase in IL-1beta at only high
      concentrations, and a decrease in MIP-1alpha expression, supporting that
      compensatory mechanisms may occur with subchronic exposure. Abeta42 levels were
      the highest in the frontal lobe of mice exposed to 992 MUg PM/m3 and tau [pS199]
      levels were elevated at the higher DE concentrations (992 and 311 MUg PM/m3) in
      both the temporal lobe and frontal lobe, indicating that proteins linked to
      preclinical Alzheimer's disease were affected. alpha Synuclein levels were
      elevated in the midbrain in response to the 992 MUg PM/m3 exposure, supporting
      that air pollution may be associated with early Parkinson's disease-like
      pathology. CONCLUSIONS: Together, the data support that the midbrain may be more
      sensitive to the neuroinflammatory effects of subchronic air pollution exposure.
      However, the DE-induced elevation of proteins associated with neurodegenerative
      diseases was limited to only the higher exposures, suggesting that air pollution
      induced neuroinflammation may precede preclinical markers of neurodegenerative
      disease in the midbrain.

PMID- 21864402
TI  - Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic
      breast cancer: results of an Austrian observational trial.
AB  - BACKGROUND: In advanced breast cancer, multiple sequential lines of treatments
      are frequently applied. Pegylated liposomal doxorubicin (PLD) has a favourable
      toxicity profile and can be used in first or higher lines of therapy. PLD has
      demonstrated response activity even after prior anthracycline exposure. METHODS:
      129 consecutive patients with advanced breast cancer, of whom the majority had
      been massively pretreated, received PLD as monotherapy within licensed approval,
      for which efficacy and toxicities were documented. RESULTS: In a routine therapy
      setting, PLD was administered in a slightly reduced dose (median, 40 mg/m2 per
      cycle). Response rate (complete and partial remission) was 26%, and stable
      disease was observed in 19% of patients. Progression-free (PFS) and overall
      survival (OS) were 5.8 months and 14.2 months, respectively. There was no
      difference in terms of response and PFS, no matter if patients had already
      received anthracycline treatment. Interestingly, PFS proved similar regardless
      whether PLD was administered as palliative therapy in first, second or third
      line. Furthermore, PFS and OS were similar in patients with response or stable
      disease, underscoring the view that disease stabilization is associated with a
      profound clinical benefit. The most common side effects reported were palmar
      plantar erythrodysesthesia (17%), exanthema (14%) and mucositis (12%).
      CONCLUSIONS: Efficacy and toxicity data in these "real life" patients permit the
      conclusion that PLD is a valuable option in the treatment of advanced breast
      cancer even in heavily pretreated patients.

PMID- 21864401
TI  - Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome
      dependent and -independent downregulation of specificity proteins (Sp)
      transcription factors.
AB  - BACKGROUND: Betulinic acid (BA) inhibits growth of several cancer cell lines and
      tumors and the effects of BA have been attributed to its mitochondriotoxicity and
      inhibition of multiple pro-oncogenic factors. Previous studies show that BA
      induces proteasome-dependent degradation of specificity protein (Sp)
      transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study
      focused on the mechanism of action of BA in colon cancer cells. METHODS: The
      effects of BA on colon cancer cell proliferation and apoptosis and tumor growth
      in vivo were determined using standardized assays. The effects of BA on Sp
      proteins and Sp-regulated gene products were analyzed by western blots, and real
      time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression.
      RESULTS: BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer
      cells and inhibited tumor growth in athymic nude mice bearing RKO cells as
      xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors
      which are overexpressed in colon cancer cells and decreased levels of several Sp
      regulated genes including survivin, vascular endothelial growth factor, p65 sub
      unit of NFkappaB, epidermal growth factor receptor, cyclin D1, and pituitary
      tumor transforming gene-1. The mechanism of action of BA was dependent on cell
      context, since BA induced proteasome-dependent and proteasome-independent
      downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO
      cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to
      induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA
      27a, and induction of the Sp repressor gene ZBTB10. CONCLUSIONS: These results
      suggest that the anticancer activity of BA in colon cancer cells is due, in part,
      to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the
      mechanism of this response is cell context-dependent.

PMID- 21864403
TI  - Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma
      microRNA biomarkers.
AB  - BACKGROUND: Making a definitive preoperative diagnosis of solitary pulmonary
      nodules (SPNs) found by CT has been a clinical challenge. We previously
      demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer
      diagnosis. Here we investigate whether plasma microRNAs are useful in identifying
      lung cancer among individuals with CT-detected SPNs. METHODS: By using
      quantitative reverse transcriptase PCR analysis, we first determine plasma
      expressions of five miRNAs in a training set of 32 patients with malignant SPNs,
      33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs
      that has high diagnostic efficiency for lung cancer. We then validate the miRNA
      panel in a testing set of 76 patients with malignant SPNs and 80 patients with
      benign SPNs. RESULTS: In the training set, miR-21 and miR-210 display higher
      plasma expression levels, whereas miR-486-5p has lower expression level in
      patients with malignant SPNs, as compared to subjects with benign SPNs and
      healthy controls (all P <= 0.001). A logistic regression model with the best
      prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three
      miRNAs used in combination produced the area under receiver operating
      characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with
      75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the
      testing set confirms their diagnostic value that yields significant improvement
      over any single one. CONCLUSIONS: The plasma miRNAs provide potential circulating
      biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs,
      and could be further evaluated in clinical trials.

PMID- 21864404
TI  - School nurses' experiences of delivering the UK HPV vaccination programme in its
      first year.
AB  - BACKGROUND: In the United Kingdom (UK) in September 2008, school nurses began
      delivering the HPV immunisation programme for girls aged 12 and 13 years old.
      This study offers insights from school nurses' perspectives and experiences of
      delivering this new vaccination programme. METHODS: Thirty in-depth telephone
      interviews were conducted with school nurses working across the UK between
      September 2008 and May 2009. This time period covers the first year of the HPV
      vaccination programme in schools. School nurses were recruited via GP practices,
      the internet and posters targeted at school nurse practitioners. RESULTS: All the
      school nurses spoke of readying themselves for a deluge of phone calls from
      concerned parents, but found that in fact few parents telephoned to ask for more
      information or express their concerns about the HPV vaccine. Several school
      nurses mentioned a lack of planning by policy makers and stated that at its
      introduction they felt ill prepared. The impact on school nurses' workload was
      spoken about at length by all the school nurses. They believed that the programme
      had vastly increased their workload leading them to cut back on their core
      activities and the time they could dedicate to offering support to vulnerable
      pupils. CONCLUSION: Overall the first year of the implementation of the HPV
      vaccination programme in the UK has exceeded school nurses' expectations and some
      of its success may be attributed to the school nurses' commitment to the
      programme. It is also the case that other factors, including positive newsprint
      media reporting that accompanied the introduction of the HPV vaccination
      programme may have played a role. Nevertheless, school nurses also believed that
      the programme had vastly increased their workload leading them to cut back on
      their core activities and as such they could no longer dedicate time to offer
      support to vulnerable pupils. This unintentional aspect of the programme may be
      worthy of further exploration.

PMID- 21864405
TI  - Evaluation of the impact of the voucher and accreditation approach on improving
      reproductive behaviors and status in Cambodia.
AB  - BACKGROUND: Cost of delivering reproductive health services to low income
      populations will always require total or partial subsidization by government
      and/or development partners. Broadly termed "demand-side financing" or "output
      based aid", these strategies include a range of interventions that channel
      government or donor subsidies to the user rather than the service provider.
      Initial pilot assessments of reproductive health voucher programs suggest that
      they can increase access, reduce inequities, and enhance program efficiency and
      service quality. However, there is a paucity of evidence describing how these
      programs function in different settings for various reproductive health services.
      METHODS/DESIGN: Population Council, funded by the Bill and Melinda Gates
      Foundation, intends to generate evidence around the "voucher and accreditation"
      approaches to improving the reproductive health of low-income women in Cambodia.
      The study comprises of four populations: facilities, providers, women of
      reproductive age using facilities, and women and men who have been pregnant
      and/or used family planning within the previous 12 months. The study will be
      carried out in a sample of 20 health facilities that are accredited to provide
      maternal and newborn health and family planning services to women holding
      vouchers from operational districts in three provinces: Kampong Thom, Kampot and
      Prey Veng and a matched sample of non-accredited facilities in three other
      provinces. Health facility assessments will be conducted at baseline and endline
      to track temporal changes in quality-of-care, client out-of-pocket costs, and
      utilization. Facility inventories, structured observations, and client exit
      interviews will be used to collect comparable data across facilities. Health
      providers will also be interviewed and observed providing care. A population
      survey of about 3000 respondents will also be conducted in areas where vouchers
      are distributed and similar non-voucher locations. DISCUSSION: A quasi
      experimental study will investigate the impact of the voucher approach on
      improving reproductive health behaviors, reproductive health status and reducing
      inequities at the population level and assess effects on access, equity and
      quality of care at the facility level. If the voucher scheme in Cambodia is found
      effective, it may help other countries adopt this approach for improving
      utilization and access to reproductive health and family planning services.

PMID- 21864406
TI  - Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1
      area: two modes of decreasing release probability.
AB  - BACKGROUND: Synaptic burst activation feeds back as a short-term depression of
      release probability at hippocampal CA3-CA1 synapses. This short-term synaptic
      plasticity requires functional astrocytes and it affects both the recently active
      (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses
      (transient heterosynaptic depression). The aim of this study was to investigate
      and compare the components contributing to the depression of release probability
      in these two different scenarios. RESULTS: When tested using paired-pulses,
      following a period of inactivity, the transient heterosynaptic depression was
      expressed as a reduction in the response to only the first pulse, whereas the
      response to the second pulse was unaffected. This selective depression of only
      the first response in a high-frequency burst was shared by the homosynaptic post
      burst depression, but it was partially counteracted by augmentation at these
      recently active synapses. In addition, the expression of the homosynaptic post
      burst depression included an astrocyte-mediated reduction of the pool of release
      ready primed vesicles. CONCLUSIONS: Our results suggest that activated astrocytes
      depress the release probability via two different mechanisms; by depression of
      vesicular release probability only at inactive synapses and by imposing a delay
      in the recovery of the primed pool of vesicles following depletion. These
      mechanisms restrict the expression of the astrocyte-mediated depression to
      temporal windows that are typical for synaptic burst activity.

PMID- 21864407
TI  - Casein SNP in Norwegian goats: additive and dominance effects on milk composition
      and quality.
AB  - BACKGROUND: The four casein proteins in goat milk are encoded by four closely
      linked casein loci (CSN1S1, CSN2, CSN1S2 and CSN3) within 250 kb on caprine
      chromosome 6. A deletion in exon 12 of CSN1S1, so far reported only in Norwegian
      goats, has been found at high frequency (0.73). Such a high frequency is
      difficult to explain because the national breeding goal selects against the
      variant's effect. METHODS: In this study, 575 goats were genotyped for 38 Single
      Nucleotide Polymorphisms (SNP) located within the four casein genes. Milk
      production records of these goats were obtained from the Norwegian Dairy Goat
      Control. Test-day mixed models with additive and dominance fixed effects of
      single SNP were fitted in a model including polygenic effects. RESULTS:
      Significant additive effects of single SNP within CSN1S1 and CSN3 were found for
      fat % and protein %, milk yield and milk taste. The allele with the deletion
      showed additive and dominance effects on protein % and fat %, and overdominance
      effects on milk quantity (kg) and lactose %. At its current frequency, the
      observed dominance (overdominance) effects of the deletion allele reduced its
      substitution effect (and additive genetic variance available for selection) in
      the population substantially. CONCLUSIONS: The selection pressure of conventional
      breeding on the allele with the deletion is limited due to the observed dominance
      (overdominance) effects. Inclusion of molecular information in the national
      breeding scheme will reduce the frequency of this deletion in the population.

PMID- 21864408
TI  - Phosphatidylinositol 3'-kinase, mTOR, and glycogen synthase kinase-3beta mediated
      regulation of p21 in human urothelial carcinoma cells.
AB  - BACKGROUND: The PTEN/Phosphatidylinositol 3'-kinase (PI3-kinase) growth factor
      signaling pathway plays a critical role in epithelial tumor development in a
      multitude of tissue types. Deletion of the Pten tumor suppressor gene in murine
      urothelial cells in vivo results in upregulation of cyclin-dependent kinase
      inhibitor p21. We have previously shown in mice that p21 expression blocks an
      increase in urothelial cell proliferation due to Pten deletion. In this study, we
      utilized human urothelial carcinoma cells UMUC-3 and UMUC-14 to identify the
      signaling pathways downstream of PI3-kinase that regulate p21. METHODS: Cells
      were treated with a combination of PI3-kinase stimulating growth factors and
      kinase inhibitors, or transfected with exogenous genes in order to identify the
      signaling events that are necessary for p21 induction. Mice with conditional
      deletion of Pten in bladder urothelium were also examined for evidence of PI3
      kinase pathway signaling events that affect p21 expression. RESULTS: When cells
      were treated with PI3-kinase activating growth factors EGF or PDGF, we found that
      p21 levels increased, in a manner similar to that observed in mice. We used the
      inhibitors LY294002, Akti-1/2, and rapamycin, to show that p21 induction is
      dependent upon PI3-kinase and AKT activity, and partially dependent on mTOR. We
      treated the cells with proteasome inhibitor MG-132 and found that p21 may be
      degraded in the proteasome to regulate protein levels. Importantly, our findings
      show that GSK-3beta plays a role in diminishing p21 levels in cells. Treatment of
      cells with the GSK-3beta inhibitor SB-216763 increased p21 levels, while
      exogenous expression of GSK-3beta caused a decrease in p21, indicating that GSK
      3beta actively reduces p21 levels. We found that a combined treatment of LY294002
      and SB-216763 improved the cytotoxic effect against UMUC-3 and UMUC-14 carcinoma
      cells over LY294002 alone, suggesting potential therapeutic uses for GSK-3beta
      inhibitors. Immunohistochemical staining in bladders from wild-type and Pten
      deleted mice indicated that GSK-3beta inhibitory phosphorylation increases when
      Pten is deleted. CONCLUSION: PI3-kinase and AKT cause an upregulation of p21 by
      suppressing GSK-3beta activity and activating mTOR in both cultured human
      urothelial carcinoma cells and mouse urothelial cells in vivo.

PMID- 21864409
TI  - Molecular changes in articular cartilage and subchondral bone in the rat anterior
      cruciate ligament transection and meniscectomized models of osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a debilitating, progressive joint disease.
      METHODS: Similar to the disease progression in humans, sequential events of early
      cartilage degradation, subchondral osteopenia followed by sclerosis, and late
      osteophyte formation were demonstrated in the anterior cruciate ligament
      transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA
      models. We describe a reliable and consistent method to examine the time
      dependent changes in the gene expression profiles in articular cartilage and
      subchondral bone. RESULTS: Local regulation of matrix degradation markers was
      demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13
      as early as the first week post-surgery, and expression remained elevated
      throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in
      differentiated chondrocytes and synovial fibroblasts at week-2 and cells within
      osteophytes at week-10 in the surgically-modified-joints. Concomitant increases
      in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion
      markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels
      at later time points in both models. Indeed, VEGF-positive cells were found in
      the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone
      resorption markers, cathepsin K and TRAP, were also elevated at week-2.
      Confirming bone resorption is an early local event in OA progression, cathepsin K
      positive osteoclasts were found invading the articular cartilage from the
      subchondral region at week 2. This was followed by late disease events, including
      subchondral sclerosis and osteophyte formation, as demonstrated by the
      upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6
      post-surgery. CONCLUSIONS: In summary, this study demonstrated the temporal and
      cohesive gene expression changes in articular cartilage and subchondral bone
      using known markers of OA progression. The findings here support genome-wide
      profiling efforts to elucidate the sequential and complex regulation of the
      disease.

PMID- 21864410
TI  - Reliability of the modified child and adolescent physical activity and nutrition
      survey, physical activity (CAPANS-PA) questionnaire among Chinese-Australian
      youth.
AB  - BACKGROUND: Evidence suggests that differences exist in physical activity (PA)
      participation among Culturally and Linguistically Diverse (CALD) children and
      adolescents. It is possible that these differences could be influenced by
      variations in measurement technique and instrument reliability. However,
      culturally sensitive instruments for examining PA behaviour among CALD
      populations are lacking. This study tested the reliability of the Child and
      Adolescent Physical Activity and Nutrition Survey (CAPANS-PA) recall
      questionnaire among a sample of Chinese-Australian youth. METHODS: The
      psychometric property of the CAPANS-PA questionnaire was examined among a sample
      of 77 Chinese-Australian youth (aged 11-14 y) who completed the questionnaire
      twice within 7 days. Test-retest reliability of individual items and scales
      within the CAPANS-PA questionnaire was determined using Kappa statistics for
      categorical variables and intraclass correlation coefficients (ICC) for
      continuous variables. RESULTS: The CAPANS-PA questionnaire demonstrated
      acceptable test-retest reliability for frequency and duration of time spent in
      weekly Moderate to Vigorous Physical Activity (MVPA) (ICC >= 0.70) for all
      participants. Test-retest reliability for time spent in weekly sedentary
      activities was acceptable for females (ICC = 0.82) and males (ICC = 0.72).
      CONCLUSIONS: The results suggest the CAPANS-PA questionnaire provides reliable
      estimates for type, frequency and duration of MVPA participation among Chinese
      Australian youth. Further investigation into the reliability of the sedentary
      items within the CAPANS-PA is required before these items can be used with
      confidence. This study is novel in that the reliability of instruments among CALD
      groups nationally and internationally remains sparse and this study contributes
      to the wider body of available psychometrically tested instruments. In addition,
      this study is the first to our knowledge to successfully engage and investigate
      the basic health enhancing behaviours of Chinese-Australian adolescents.

PMID- 21864411
TI  - Comparison of the virulence of exopolysaccharide-producing Prevotella intermedia
      to exopolysaccharide non-producing periodontopathic organisms.
AB  - BACKGROUND: Evidence in the literature suggests that exopolysaccharides (EPS)
      produced by bacterial cells are essential for the expression of virulence in
      these organisms. Secreted EPSs form the framework in which microbial biofilms are
      built. METHODS: This study evaluates the role of EPS in Prevotella intermedia for
      the expression of virulence. This evaluation was accomplished by comparing EPS
      producing P. intermedia strains 17 and OD1-16 with non-producing P. intermedia
      ATCC 25611 and Porphyromonas gingivalis strains ATCC 33277, 381 and W83 for their
      ability to induce abscess formation in mice and evade phagocytosis. RESULTS: EPS
      producing P. intermedia strains 17 and OD1-16 induced highly noticeable abscess
      lesions in mice at 107 colony-forming units (CFU). In comparison, P. intermedia
      ATCC 25611 and P. gingivalis ATCC 33277, 381 and W83, which all lacked the
      ability to produce viscous materials, required 100-fold more bacteria (109 CFU)
      in order to induce detectable abscess lesions in mice. Regarding antiphagocytic
      activity, P. intermedia strains 17 and OD1-16 were rarely internalized by human
      polymorphonuclear leukocytes, but other strains were readily engulfed and
      detected in the phagosomes of these phagocytes. CONCLUSIONS: These results
      demonstrate that the production of EPS by P. intermedia strains 17 and OD1-16
      could contribute to the pathogenicity of this organism by conferring their
      ability to evade the host's innate defence response.

PMID- 21864412
TI  - Socio-demographic, psychosocial and home-environmental attributes associated with
      adults' domestic screen time.
AB  - BACKGROUND: Sedentary behaviors (involving prolonged sitting time) are associated
      with deleterious health consequences, independent of (lack of) physical activity.
      To inform interventions, correlates of prevalent sedentary behaviors need to be
      identified. We examined associations of socio-demographic, home-environmental and
      psychosocial factors with adults' TV viewing time and leisure-time Internet use;
      and whether psychosocial and environmental correlates differed according to
      gender, age and educational attainment. METHODS: This cross-sectional study was
      conducted in Ghent, Belgium, between March and May 2010. Respondents to a mail
      out survey (n = 419; 20-65 years; mean age 48.5 [12.1] years; 47.3% men)
      completed a questionnaire on sedentary behaviors and their potential socio
      demographic, psychosocial and home environmental correlates. Statistical analyses
      were performed using multiple linear regression models. RESULTS: The independent
      variables explained 31% of the variance in TV viewing time and 38% of the
      variance in leisure-time Internet use. Higher education, greater perceived pros
      of and confidence about reducing TV time were negatively associated with TV
      viewing time; older age, higher body mass index, larger TV set size and greater
      perceived cons of reducing TV time showed positive associations. Perceived pros
      of and confidence about reducing Internet use were negatively associated with
      leisure-time Internet use; higher education, number of computers in the home,
      positive family social norms about Internet use and perceived cons of reducing
      Internet use showed positive associations. None of the socio-demographic factors
      moderated these associations. CONCLUSIONS: Educational level, age, self-efficacy
      and pros/cons were the most important correlates identified in this study. If
      further cross-sectional and longitudinal research can confirm these findings,
      tailored interventions focusing on both psychosocial and environmental factors in
      specific population subgroups might be most effective to reduce domestic screen
      time.

PMID- 21864413
TI  - Early complications after biliary enteric anastomosis for benign diseases: a
      retrospective analysis.
AB  - BACKGROUND: Biliary-enteric anastomosis (BEA) is a common surgical procedure
      performed for the management of biliary obstruction or leakage that results from
      a variety of benign and malignant diseases. Complications following BEA are not
      rare. We aimed to determine the incidence and the factors associated with early
      complications occurring after BEA for benign diseases. METHODS: We reviewed the
      medical records of all patients who underwent BEA for benign diseases at our
      institution between January 1988 and December 2009. The primary outcome was early
      post operative complication. Logistic regression analysis was done to identify
      factors predicting the occurrence of complications. RESULTS: Records of 79
      patients were reviewed. There were 34 (43%) males and 45 (57% females). Majority
      (53%) had choledocholithiasis with impacted stone or distal stricture, followed
      by traumatic injury to the biliary system (33%). Thirty-four patients (43%)
      underwent a hepaticojejunostomy, 19 patients (24%) underwent a
      choledochojejunostomy, and choledochoduodenostomy was performed in 26 patients
      (33%). Early complications occurred in 39 (49%) patients - 41% had local
      complications and 25% had systemic complications. Most frequent complications
      were wound infection (23%) and bile leak (10%). Four (5%) patients died. On
      multivariate analysis, low serum albumin level (odds ratio = 16, 95% CI = 1.14
      234.6) and higher ASA levels (odds ratio = 7, 95% CI: 1.22-33.34) were the
      independent factors predicting the early complications following BEA.
      CONCLUSIONS: Half of the patients who underwent BEA for benign diseases had
      complications in our population. This high incidence may be explained by the high
      incidence of hypoalbuminemia and the high-risk group who underwent operation.

PMID- 21864415
TI  - Differential transcriptomic profiles effected by oil palm phenolics indicate
      novel health outcomes.
AB  - BACKGROUND: Plant phenolics are important nutritional antioxidants which could
      aid in overcoming chronic diseases such as cardiovascular disease and cancer, two
      leading causes of death in the world. The oil palm (Elaeis guineensis) is a rich
      source of water-soluble phenolics which have high antioxidant activities. This
      study aimed to identify the in vivo effects and molecular mechanisms involved in
      the biological activities of oil palm phenolics (OPP) during healthy states via
      microarray gene expression profiling, using mice supplemented with a normal diet
      as biological models. RESULTS: Having confirmed via histology, haematology and
      clinical biochemistry analyses that OPP is not toxic to mice, we further explored
      the gene expression changes caused by OPP through statistical and functional
      analyses using Illumina microarrays. OPP showed numerous biological activities in
      three major organs of mice, the liver, spleen and heart. In livers of mice given
      OPP, four lipid catabolism genes were up-regulated while five cholesterol
      biosynthesis genes were down-regulated, suggesting that OPP may play a role in
      reducing cardiovascular disease. OPP also up-regulated eighteen blood coagulation
      genes in spleens of mice. OPP elicited gene expression changes similar to the
      effects of caloric restriction in the hearts of mice supplemented with OPP.
      Microarray gene expression fold changes for six target genes in the three major
      organs tested were validated with real-time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR), and the correlation of fold changes obtained
      with these two techniques was high (R2 = 0.9653). CONCLUSIONS: OPP showed non
      toxicity and various pleiotropic effects in mice. This study implies the
      potential application of OPP as a valuable source of wellness nutraceuticals, and
      further suggests the molecular mechanisms as to how dietary phenolics work in
      vivo.

PMID- 21864416
TI  - Effects of a Chinese medical herbs complex on cellular immunity and toxicity
      related conditions of breast cancer patients.
AB  - Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti
      inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae
      (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis
      (Apiaceae) are traditional Chinese herbs associated with immunomodulatory
      functions. In the present study, a randomised, double-blind, placebo-controlled
      study was conducted to examine whether the Chinese medicinal herb complex, RG
      CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C.
      pilosula and A. sinensis, can improve the immune cell count of cancer patients
      receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune
      impairment that usually occurs during cancer therapy. A total of fifty-eight
      breast cancer patients who received chemotherapy or radiotherapy were enrolled.
      Immune cell levels in patient serum were determined before, and following, 6
      weeks of cancer treatment for patients receiving either an RG-CMH or a placebo.
      Administration of RG-CMH was associated with a significant reduction in levels of
      leucocytes from 31.5 % for the placebo group to 13.4 % for the RG-CMH group.
      Similarly, levels of neutrophils significantly decreased from 35.6 % for the
      placebo group to 11.0 % for the RG-CMH group. RG-CMH intervention was also
      associated with a decrease in levels of T cells, helper T cells, cytotoxic T
      cells and natural killer cells compared with the placebo group. However, these
      differences between the two groups were not statistically significant. In
      conclusion, administration of RG-CMH to patients receiving
      chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction
      in levels of leucocytes and neutrophils that are experienced by patients during
      cancer treatment.

PMID- 21864414
TI  - The relaxation exercise and social support trial-resst: study protocol for a
      randomized community based trial.
AB  - BACKGROUND: Studies suggests a possible link between vaginal discharge and common
      mental distress, as well as highlight the implications of the subjective burden
      of disease and its link with mental health. METHODS/DESIGN: This is a community
      based intervention trial that aims to evaluate the impact of a psycho-social
      intervention on medically unexplained vaginal discharge (MUVD) in a group of
      married, low-income Lebanese women, aged 18-49, and suffering from low to
      moderate levels of anxiety and/or depression. The intervention consisted of 12
      sessions of structured social support, problem solving techniques, group
      discussions and trainer-supervised relaxation exercises (twice per week over six
      weeks). Women were recruited from Hey el Selloum, a southern disadvantaged suburb
      of Beirut, Lebanon, during an open recruitment campaign. The primary outcome was
      self-reported MUVD, upon ruling out reproductive tract infections (RTIs), through
      lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for
      this trial. These were assessed using an Arabic validated version of the Hopkins
      Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months
      using face-to face interviews, pelvic examinations and laboratory tests. Women
      were randomized into either intervention or control group. Intent to treat
      analysis will be used. DISCUSSION: The results will indicate whether the proposed
      psychosocial intervention was effective in reducing MUVD (possibly mediated by
      common mental distress). TRIAL REGISTRATION: The trial is registered at the
      Wellcome Trust Registry, ISRCTN assigned: ISRCTN: ISRCTN98441241.

PMID- 21864417
TI  - No effect of 12 weeks' supplementation with 1 g DHA-rich or EPA-rich fish oil on
      cognitive function or mood in healthy young adults aged 18-35 years.
AB  - The n-3 PUFA are a unique class of fatty acids that cannot be manufactured by the
      body, and must be acquired via dietary sources. In the UK, as well as in other
      Western nations, these 'essential' fatty acids are consumed in quantities that
      fall below government guidelines. The present study explored the effects of 12
      weeks' dietary supplementation with 1 g/d of two types of fish oil (FO; DHA-rich
      and EPA-rich) in 159 healthy young adults aged 18-35 years. An assessment of
      performance on a battery of computerised cognitive tasks and mood measures took
      place before and following the 12-week treatment regimen. Venous blood samples
      were also supplied by participants at both time points which were later analysed
      for serum fatty acid concentrations. Despite good adherence to the study protocol
      - as reflected in increased concentrations of n-3 serum fatty acids - compared
      with placebo, the observed effects of both active treatments were minimal. The
      only finding of note revealed that supplementation with EPA-rich FO may reduce
      subjective mental fatigue at times of high cognitive demand, although further
      investigation is required. These findings, taken together with other recent
      reports of null effects, suggest that dietary supplementation with n-3 PUFA in
      healthy, normally developing and impairment-free populations is unlikely to
      result in cognitive enhancement.

PMID- 21864418
TI  - Inhibition of advanced glycation end-product formation on eye lens protein by
      rutin.
AB  - Formation of advanced glycation end products (AGE) plays a key role in the
      several pathophysiologies associated with ageing and diabetes, such as arthritis,
      atherosclerosis, chronic renal insufficiency, Alzheimer's disease, nephropathy,
      neuropathy and cataract. This raises the possibility of inhibition of AGE
      formation as one of the approaches to prevent or arrest the progression of
      diabetic complications. Previously, we have reported that some common dietary
      sources such as fruits, vegetables, herbs and spices have the potential to
      inhibit AGE formation. Flavonoids are abundantly found in fruits, vegetables,
      herbs and spices, and rutin is one of the commonly found dietary flavonols. In
      the present study, we have demonstrated the antiglycating potential and mechanism
      of action of rutin using goat eye lens proteins as model proteins. Under in vitro
      conditions, rutin inhibited glycation as assessed by SDS-PAGE, AGE-fluorescence,
      boronate affinity chromatography and immunodetection of specific AGE. Further, we
      provided insight into the mechanism of inhibition of protein glycation that rutin
      not only scavenges free-radicals directly but also chelates the metal ions by
      forming complexes with them and thereby partly inhibiting post-Amadori formation.
      These findings indicate the potential of rutin to prevent and/or inhibit protein
      glycation and the prospects for controlling AGE-mediated diabetic pathological
      conditions in vivo.

PMID- 21864419
TI  - Bayesian Fundamentalism or Enlightenment? On the explanatory status and
      theoretical contributions of Bayesian models of cognition.
AB  - The prominence of Bayesian modeling of cognition has increased recently largely
      because of mathematical advances in specifying and deriving predictions from
      complex probabilistic models. Much of this research aims to demonstrate that
      cognitive behavior can be explained from rational principles alone, without
      recourse to psychological or neurological processes and representations. We note
      commonalities between this rational approach and other movements in psychology -
      namely, Behaviorism and evolutionary psychology - that set aside mechanistic
      explanations or make use of optimality assumptions. Through these comparisons, we
      identify a number of challenges that limit the rational program's potential
      contribution to psychological theory. Specifically, rational Bayesian models are
      significantly unconstrained, both because they are uninformed by a wide range of
      process-level data and because their assumptions about the environment are
      generally not grounded in empirical measurement. The psychological implications
      of most Bayesian models are also unclear. Bayesian inference itself is
      conceptually trivial, but strong assumptions are often embedded in the hypothesis
      sets and the approximation algorithms used to derive model predictions, without a
      clear delineation between psychological commitments and implementational details.
      Comparing multiple Bayesian models of the same task is rare, as is the
      realization that many Bayesian models recapitulate existing (mechanistic level)
      theories. Despite the expressive power of current Bayesian models, we argue they
      must be developed in conjunction with mechanistic considerations to offer
      substantive explanations of cognition. We lay out several means for such an
      integration, which take into account the representations on which Bayesian
      inference operates, as well as the algorithms and heuristics that carry it out.
      We argue this unification will better facilitate lasting contributions to
      psychological theory, avoiding the pitfalls that have plagued previous
      theoretical movements.

PMID- 21864447
TI  - High contrast magnetic and nonmagnetic sample current microscopy for bulk and
      transparent samples using soft X-rays.
AB  - The soft X-ray energy range provides important detection capabilities for a wide
      range of material systems, e.g., the K-edge behavior of biological materials or
      magnetic contrast imaging at the L2,3- and M4,5-edges, respectively, using the X
      ray magnetic circular dichroism effect. The need for thinned samples due to the
      short penetration depth of soft X-rays is a limiting factor for microscopic
      imaging in transmission microscopy. In contrast, the more surface sensitive
      photoelectron emission microscopy allows the X-ray microscopic investigation of
      nontransparent bulk samples, but only small magnetic fields and very smooth
      surfaces are possible. As both high magnetic fields as well as bulk samples are
      important for magnetic imaging, we present total electron yield (TEY) microscopy
      results using the total sample current detection performed at the new ultra high
      vacuum scanning microscope "MAXYMUS" at HZB/BESSY II. We compare synchronous
      measurements in TEY and transmission mode to demonstrate the capabilities of TEY
      microscopy. Pictures and spectra with high absorption contrast and three
      dimensional-like edge enhancement are observed as known for scanning electron
      microscopy. This unveils details on smallest length scales of the surface
      morphology. Furthermore, surface sensitive in- and out-of-plane magnetic TEY
      measurements at nontransparent samples are shown.

PMID- 21864448
TI  - The influences of metabotropic receptor activation on cellular signaling and
      synaptic function in amacrine cells.
AB  - Amacrine cells receive glutamatergic input from bipolar cells and GABAergic,
      glycinergic, cholinergic, and dopaminergic input from other amacrine cells.
      Glutamate, GABA, glycine, and acetylcholine (ACh) interact with ionotropic
      receptors and it is these interactions that form much of the functional circuitry
      in the inner retina. However, glutamate, GABA, ACh, and dopamine also activate
      metabotropic receptors linked to second messenger pathways that have the
      potential to modify the function of individual cells as well as retinal
      circuitry. Here, the physiological effects of activating dopamine receptors,
      metabotropic glutamate receptors, GABAB receptors, and muscarinic ACh receptors
      on amacrine cells will be discussed. The retina also expresses metabotropic
      receptors and the biochemical machinery associated with the synthesis and
      degradation of endocannabinoids and sphingosine-1-phosphate (S1P). The effects of
      activating cannabinoid receptors and S1P receptors on amacrine cell function will
      also be addressed.

PMID- 21864450
TI  - Acquired ventricular septal aneurysm in a patient with pulmonary atresia with
      intact ventricular septum.
AB  - Myocardial ischaemia and infarction in pulmonary atresia and intact ventricular
      septum with right ventricular-dependent coronary circulation is a well
      established complication. We report an interesting case of an acquired aneurysm
      in the ventricular septum in a patient who underwent staged palliation.

PMID- 21864449
TI  - Genetic targeting and physiological features of VGLUT3+ amacrine cells.
AB  - Amacrine cells constitute a diverse class of interneurons that contribute to
      visual signal processing in the inner retina, but surprisingly, little is known
      about the physiology of most amacrine cell subtypes. Here, we have taken
      advantage of the sparse expression of vesicular glutamate transporter 3 (VGLUT3)
      in the mammalian retina to target the expression of yellow fluorescent protein
      (YFP) to a unique population of amacrine cells using a new transgenic mouse line.
      Electrophysiological recordings made from YFP-positive (VGLUT3+) amacrine cells
      provide the first functional data regarding the active membrane properties and
      synaptic connections of this recently identified cell type. We found that VGLUT3+
      amacrine cells receive direct synaptic input from bipolar cells via both N-methyl
      d-aspartate receptors (NMDARs) and non-NMDARs. Voltage-gated sodium channels
      amplified these excitatory inputs but repetitive spiking was never observed.
      VGLUT3+ amacrine cells responded transiently to both light increments (ON
      response) and decrements (OFF response); ON responses consisted exclusively of
      inhibitory inputs, while OFF responses comprised both excitatory and inhibitory
      components, although the inhibitory conductance was larger in amplitude and
      longer in time course. The physiological properties and anatomical features of
      the VGLUT3+ amacrine cells suggest that this bistratified interneuron may play a
      role in disinhibitory signaling and/or crossover inhibition between parallel
      pathways in the retina.

PMID- 21864451
TI  - Effects of atomoxetine on cardiovascular functions and on QT dispersion in
      children with attention deficit hyperactivity disorder.
AB  - BACKGROUND: Atomoxetine is a central norepinephrine reuptake inhibitor used to
      treat attention deficit/hyperactivity disorder. The effects of atomoxetine on
      cardiovascular functions and QT dispersion in children with attention
      deficit/hyperactivity disorder have not been previously reported. The aim of this
      study was to analyse cardiovascular functions and QT dispersion on the surface
      electrocardiogram of children with attention deficit/hyperactivity disorder
      during atomoxetine therapy. METHODS: A total of 40 children - with a mean age of
      8.6 plus or minus 2.3 years and a median age of 11 years; ranged from 8 to 14
      years - with attention deficit/hyperactivity disorder - with six girls and 34
      boys - were included in the study. We recorded the mean systolic and diastolic
      blood pressure, heart rate, corrected QT interval, QT dispersion, and left
      ventricular systolic functions at baseline and 5 weeks after atomoxetine therapy.
      RESULTS: Atomoxetine decreased baseline mean systolic and diastolic blood
      pressure; baseline mean heart rate decreased; and baseline mean corrected QT
      interval and QT dispersion mildly increased. Atomoxetine decreased baseline mean
      ejection fraction and baseline mean shortening fraction. CONCLUSION: The results
      of our study suggest that atomoxetine does not cause clinically significant
      alterations in QT dispersion, systolic and diastolic blood pressure, heart rate,
      corrected QT interval, and left ventricular systolic functions during short-term
      treatment in children with attention deficit/hyperactivity disorder.

PMID- 21864453
TI  - Statistical significance testing with mahalanobis distance for thresholds
      estimated from constant stimuli method.
AB  - The t-test and the analysis of variance are commonly used as statistical
      significance testing methods. However, they cannot assess the significance of
      differences between thresholds within individual observers estimated from the
      constant stimuli method; these thresholds are not defined as averages of samples,
      but they are rather defined as functions of parameters of psychometric functions
      fitted to participants' responses. Moreover, the statistics necessary for these
      statistical testing methods cannot be derived. In this paper, we propose a new
      statistical testing method to assess the statistical significance of differences
      between thresholds estimated from the constant stimuli method. The new method can
      assess not only threshold differences but also main effects and interactions in
      multifactor experiments, exploiting the asymptotic normality of maximum
      likelihood estimators and the characteristics of multivariate normal
      distributions. This proposed method could be used in similar cases to the
      analysis of variance for thresholds estimated from the adjustment method and the
      staircase method. Finally, we present some data on simulations in which we tested
      assumptions, power and type I error of the proposed method.

PMID- 21864454
TI  - Estimating the position of simulated phosphenes using a tactile guide.
AB  - A visual prosthesis provides usable visual information to the patient in the form
      of phosphenes, that is, punctate photic sensations seen after electrical
      stimulation. Stimulation via different electrodes results in phosphenes in
      different positions within the visual field. Simulation studies can provide data
      on the possible limitations of prosthetic stimulation. We used a head mounted
      screen to monocularly present constant or flickering light spots of different
      sizes, or luminance to normally sighted subjects. Subjects were asked to judge
      the location of the spots using a polar coordinate tactile guide; positioning
      average error and dispersion were analyzed. With the increase of eccentricity,
      the positioning average error and dispersion were also increased. The
      performances under large, stable and high luminance conditions were better than
      that under small, flickering and low luminance conditions, respectively. Repeated
      training sessions were shown to significantly improve the positioning
      performance.

PMID- 21864452
TI  - Mutations in ZIC3 and ACVR2B are a common cause of heterotaxy and associated
      cardiovascular anomalies.
AB  - BACKGROUND: Heterotaxy syndrome is caused by left-right asymmetry disturbances
      and is associated with abnormal lateralisation of the abdominal and thoracic
      organs. The heart is frequently involved and the severity of the abnormality
      usually determines the outcome. METHODS: We performed a direct sequence analysis
      of the coding sequence of genes including Zinc Finger Protein of the Cerebellum
      3, Left-Right Determination Factor 2, Activin A Receptor Type IIB, and Cryptic in
      47 patients with laterality defects and congenital cardiac disease. RESULTS: Of
      the 47 patients, 31 (66%) had atrioventricular septal defects, 34 (72%) had
      abnormal systemic venous return, 25 (53%) had transposed or malposed great
      arteries, and 20 (43%) had pulmonary venous abnormalities. We identified two
      novel genetic changes in Zinc Finger Protein of the Cerebellum 3, and these
      variants were not present in 100 ethnically matched control samples. One
      previously reported missense mutation in Activin A Receptor Type IIB was
      identified in two unrelated subjects. The genetic changes identified in this
      study are all located in conserved regions and are predicted to affect protein
      function in left-right axis formation and cardiovascular development.
      CONCLUSIONS: Mutations in Zinc Finger Protein of the Cerebellum 3 and Activin A
      Receptor Type IIB were identified in 4 of the 47 patients with heterotaxy
      syndrome for a yield of approximately 8.5%. Our results expand the mutation
      spectrum of monogenic heterotaxy syndrome with associated cardiac anomalies and
      suggest that there are other causes of heterotaxy yet to be identified.

PMID- 21864455
TI  - Adaptation affects both high and low (subitized) numbers under conditions of high
      attentional load.
AB  - It has recently been reported that, like most sensory systems, numerosity is
      subject to adaptation. However, the effect seemed to be limited to numerosity
      estimation outside the subitizing range. In this study we show that low numbers,
      clearly in the subitizing range, are adaptable under conditions of high
      attentional load. These results support the idea that numerosity is detected by a
      perceptual mechanism that operates over the entire range of numbers, supplemented
      by an attention-based system for small numbers (subitizing).

PMID- 21864456
TI  - Letter posting and orientation matching: two equivalent tasks in action and
      perception?
AB  - The finding that in a patient with visual form agnosia (DF), the performance
      level varies in a visuomotor letter-posting task and a perceptual orientation
      matching task was considered as part of the evidence for the perception-action
      model (Milner and Goodale, 1995). In this study we examined an alternative
      interpretation of these findings. We specifically tested whether orientation
      matching and letter posting can be accomplished using different strategies.
      Sixteen neurologically intact participants were asked to either put cards of
      different sizes through a target slot of a certain orientation or to simply
      indicate the slot's orientation. Letter-posting was performed in three different
      conditions varying the amount of visual feedback available. Results show that
      some participants apply a strategy of obstacle-avoidance in the posting task.
      That is, they oriented the card such that the safety margin between the edges of
      the target and the card was increased. This tendency became stronger with
      increasing card size. In contrast, in the orientation matching task, the end
      orientation of the card was unaffected by its size and closer to the slot's
      actual orientation. The findings suggest that posting and matching can be solved
      using different visuo-spatial information. The perception-action dissociation
      reported for these tasks in DF might therefore simply indicate a difficulty in
      computing visual orientation, an ability that is needed for successful
      orientation matching but not for posting.

PMID- 21864457
TI  - Simulated viewpoint jitter shakes sensory conflict accounts of vection.
AB  - Sensory conflict has been used to explain the way we perceive and control our
      self-motion, as well as the aetiology of motion sickness. However, recent
      research on simulated viewpoint jitter provides a strong challenge to one core
      prediction of these theories -- that increasing sensory conflict should always
      impair visually induced illusions of self-motion (known as vection). These
      studies show that jittering self-motion displays (thought to generate significant
      and sustained visual-vestibular conflict) actually induce superior vection to
      comparable non-jittering displays (thought to generate only minimal/transient
      sensory conflict). Here we review viewpoint jitter effects on vection, postural
      sway, eye-movements and motion sickness, and relate them to recent behavioural
      and neurophysiological findings. It is shown that jitter research provides
      important insights into the role that sensory interaction plays in self-motion
      perception.

PMID- 21864458
TI  - Partitioning contrast or luminance disparity into perceived intensity and
      rotation.
AB  - While most of the work on stereopsis focuses on geometric disparities, humans
      also respond to intensity (contrast or luminance) disparities in the absence of
      geometric disparities. A rectangular-wave grating viewed with an intensity
      disparity engenders two perceptions: a perceived intensity, and a perceived
      rotation of the individual bars of the grating (the Venetian blind effect).
      Measuring perceived intensity and perceived rotation in gratings with intensity
      disparities, we found that the two degrees of freedom from the intensities
      presented to each eye are conserved in the form of two perceptions: perceived
      intensity is related to the sum of the grating intensities and perceived rotation
      is related to the difference. Perceived rotation as a function of intensity
      disparity was then modeled as a simple difference in the neural response of each
      eye. Perceived contrast and brightness as a function of intensity disparity were
      modeled using the two-stage gain-control model.

PMID- 21864459
TI  - Cerebral correlates and statistical criteria of cross-modal face and voice
      integration.
AB  - Perception of faces and voices plays a prominent role in human social
      interaction, making multisensory integration of cross-modal speech a topic of
      great interest in cognitive neuroscience. How to define potential sites of
      multisensory integration using functional magnetic resonance imaging (fMRI) is
      currently under debate, with three statistical criteria frequently used (e.g.,
      super-additive, max and mean criteria). In the present fMRI study, 20
      participants were scanned in a block design under three stimulus conditions:
      dynamic unimodal face, unimodal voice and bimodal face-voice. Using this single
      dataset, we examine all these statistical criteria in an attempt to define loci
      of face-voice integration. While the super-additive and mean criteria essentially
      revealed regions in which one of the unimodal responses was a deactivation, the
      max criterion appeared stringent and only highlighted the left hippocampus as a
      potential site of face- voice integration. Psychophysiological interaction
      analysis showed that connectivity between occipital and temporal cortices
      increased during bimodal compared to unimodal conditions. We concluded that, when
      investigating multisensory integration with fMRI, all these criteria should be
      used in conjunction with manipulation of stimulus signal-to-noise ratio and/or
      cross-modal congruency.

PMID- 21864460
TI  - Capture of intermodal visual/tactile apparent motion by moving and static sound.
AB  - Apparent motion can occur within a particular modality or between modalities, in
      which a visual or tactile stimulus at one location is perceived as moving towards
      the location of the subsequent tactile or visual stimulus. Intramodal apparent
      motion has been shown to be affected or 'captured' by information from another,
      task-irrelevant modality, as in spatial or temporal ventriloquism. Here we
      investigate whether and how intermodal apparent motion is affected by motion
      direction cues or temporal interval information from a third modality. We
      demonstrated that both moving and asynchronous static sounds can capture
      intermodal (visual-tactile and tactile-visual) apparent motion; moreover, while
      the auditory direction cues have less impact upon the perception of intramodal
      visual apparent motion than upon the perception of intramodal tactile or
      intermodal visual/tactile apparent motion, the auditory temporal information has
      equivalent impacts upon both intramodal and intermodal apparent motion. These
      findings suggest intermodal apparent motion is susceptible to the influence of
      dynamic or static auditory information in similar ways as intramodal visual or
      tactile apparent motion.

PMID- 21864462
TI  - Seeing and Perceiving is announcing the change of the North American editor,
      introduction.

PMID- 21864461
TI  - Anomalous Auditory Cortex Activations in Colored Hearing Synaesthetes: An fMRI
      Study.
AB  - Color percept induction in synaesthetes by hearing words was previously shown to
      involve activation of visual and specifically color processing cortex areas.
      While this provides a rationale for the origin of the anomalous color percept the
      question of mechanism of this crossmodal activation remains unclear. We pursued
      this question with fMRI in color hearing synaesthetes by exposing subjects to
      words and tones. Brain activations in word condition accompanied by highly
      reliable color percepts were compared with activations in tone condition with
      only occasional color percepts and both contrasted to activations in normal
      subjects under the same stimulus conditions. This revealed that already the tone
      condition similar to the word condition caused abnormally high activations in
      various cortical areas even though synaesthetic percepts were more rare. Such
      tone activations were significantly larger than in normal subjects in visual
      areas of the right occipital lobe, the fusiform gyrus, and the left middle
      temporal gyrus and in auditory areas of the left superior temporal gyrus. These
      auditory areas showed strong word and tone activation alike and not the typically
      lower tone than word activation in normal subjects. Taken together these results
      are interpreted in favour of the disinhibited feedback hypothesis as the
      neurophysiological basis of genuine synaesthesia.

PMID- 21864463
TI  - Self-motion reproduction can be affected by associated auditory cues.
AB  - Successful locomotion through space requires precise estimation of the direction
      and distance travelled. Previous studies have shown that humans can use velocity
      information arising from visual, vestibular and somatosensory signals to
      reproduce passive linear displacements. In the present study we investigated
      whether also associated auditory velocity cues are used for distance estimation.
      Subjects had to reproduce (active condition) the distance of a previously seen
      sequence of simulated linear motion (passive condition) across a ground plane.
      During both, the passive and active displacement, they heard a tone with a
      frequency being proportional to the simulated speed (test trials). In some trials
      the relationship between optical velocity and tone frequency was differently
      scaled during the active displacements, i.e., the frequency of the tone was
      either higher or lower than in the passive displacement (catch trials). In test
      trials, subjects reproduced distances quite accurately. In catch trials, however,
      subjects' performance was disturbed: when the frequency was lower subjects used
      higher speeds, resulting in a substantial overshoot of travelled distance,
      whereas a higher frequency resulted in an undershoot of travelled distance. Our
      results clearly show that during self-motion tone frequency can be used as a
      velocity cue and helps to update positional information over time.

PMID- 21864464
TI  - Goal-directed reaching: the SNARC effect influences movement planning but not
      movement execution.
AB  - The spatial-numerical association of response codes (SNARC effect) is a well
      documented phenomenon wherein numerical digits spatially bias the selection of a
      response, with low and high numbers eliciting faster left and right responses,
      respectively. A host of button press tasks report expression of the SNARC effect
      for response planning (i.e., reaction time: RT); however, Fischer (2003) reports
      that the effect can selectively manifest during the movement execution phase
      (i.e., movement time: MT) of a goal-directed reaching task. Here we employed a
      kinematic technique to determine whether the reported SNARC effect is expressed
      in the early or late (or both) stages of a goal-directed reaching trajectory.
      Results for RT produced a reliable SNARC effect whereas results for MT produced a
      reversed-SNARC effect that was attributed to the deceleration phase of reach
      trajectories. More specifically, left space reaches cued by low numbers produced
      shorter RTs than high number counterparts and were associated with longer MTs
      (the converse was true of right space reaches). We have interpreted these results
      in terms of a spatial-numerical bias influencing a trade-off between the temporal
      properties of movement planning and execution mechanisms.

PMID- 21864465
TI  - An investigation of the Venetian blind effect.
AB  - When a rectangular wave grating is binocularly viewed with a neutral density
      filter over one eye, an illusory rotation resembling that of a partially opened
      Venetian blind is perceived (Cibis and Haber, 1951). Using a binary
      classification task, in the first experiment, the probability of perceiving a
      rotation in a given direction was measured as a function of a factorial
      combination of inter-ocular contrast (see Note 1) and luminance ratios. The
      probability of a rotation in a given direction decreased monotonically with the
      luminance of the brighter bars when the grating contains a less than unity
      contrast. This result is inconsistent with (i) the model of the Venetian blind
      effect proposed by Cibis and Haber (1951), (ii) a mechanism based on irradiation
      with a compressive non-linearity (von Helmholtz, 1911/1924, pp. 186-193) and
      (iii) contemporary stereo-energy/cross-correlation models of stereopsis. In the
      second and third experiments, we tested the prediction that irradiation combined
      with an early compressive non-linearity in response implies a positive
      relationship between both the threshold contrast or average luminance disparity
      to perceive rotation and the magnitude of perceived rotation, and the blur width
      at the bar's edge. No support was found for the prediction. We propose an
      intensity difference model of the probability of perceiving a rotation in a given
      direction as a function of the interocular difference in luminance or contrast.

PMID- 21864466
TI  - An investigation into the cause of orientation-sensitivity in haptic object
      recognition.
AB  - Object orientation influences visual and haptic recognition differently. This
      could be caused by the two modalities accessing different object representations
      or it could be due to differences in how each modality acquires information.
      These two alternatives were investigated using sequential haptic matching tasks.
      Matches presented the same object twice. Mismatches presented two similarly
      shaped objects. Objects were either both placed at the same orientation or were
      rotated 90 degrees  in depth from each other. Experiment 1 manipulated
      exploration time to test if longer durations weakened orientation-sensitivity by
      allowing orientation-invariant representations to be extracted. This hypothesis
      was not supported. Experiment 2 investigated whether the same-orientation
      advantage resulted from general spatial or motor action cueing rather than the
      involvement of orientation-specific object representations. To distinguish
      between these two possibilities, people did a secondary task interleaved within
      the matching task. They reported the orientation of a fork or spoon which was
      presented in between the first and second objects. The main axis of the
      fork/spoon was the same as that of the final object, equating spatial and motor
      cueing across the same-orientation and orientation-change conditions.
      Nevertheless, matching remained orientation-sensitive. Together these results
      suggest that there are separate visual and haptic stored, orientation-specific
      perceptual representations of objects.

PMID- 21864467
TI  - Bright light for nonseasonal depression?

PMID- 21864468
TI  - Inflaming depression.

PMID- 21864469
TI  - Hearing aids and auditory localization.

PMID- 21864470
TI  - Evaluation of auditory functions for Royal Canadian Mounted Police officers.
AB  - BACKGROUND: Auditory fitness for duty (AFFD) testing is an important element in
      an assessment of workers' ability to perform job tasks safely and effectively.
      Functional hearing is particularly critical to job performance in law
      enforcement. Most often, assessment is based on pure-tone detection thresholds;
      however, its validity can be questioned and challenged in court. In an attempt to
      move beyond the pure-tone audiogram, some organizations like the Royal Canadian
      Mounted Police (RCMP) are incorporating additional testing to supplement
      audiometric data in their AFFD protocols, such as measurements of speech
      recognition in quiet and/or in noise, and sound localization. PURPOSE: This
      article reports on the assessment of RCMP officers wearing hearing aids in speech
      recognition and sound localization tasks. The purpose was to quantify individual
      performance in different domains of hearing identified as necessary components of
      fitness for duty, and to document the type of hearing aids prescribed in the
      field and their benefit for functional hearing. The data are to help RCMP in
      making more informed decisions regarding AFFD in officers wearing hearing aids.
      RESEARCH DESIGN: The proposed new AFFD protocol included unaided and aided
      measures of speech recognition in quiet and in noise using the Hearing in Noise
      Test (HINT) and sound localization in the left/right (L/R) and front/back (F/B)
      horizontal planes. Sixty-four officers were identified and selected by the RCMP
      to take part in this study on the basis of hearing thresholds exceeding current
      audiometrically based criteria. This article reports the results of 57 officers
      wearing hearing aids. RESULTS: Based on individual results, 49% of officers were
      reclassified from nonoperational status to operational with limitations on fine
      hearing duties, given their unaided and/or aided performance. Group data revealed
      that hearing aids (1) improved speech recognition thresholds on the HINT, the
      effects being most prominent in Quiet and in conditions of spatial separation
      between target and noise (Noise Right and Noise Left) and least considerable in
      Noise Front; (2) neither significantly improved nor impeded L/R localization; and
      (3) substantially increased F/B errors in localization in a number of cases.
      Additional analyses also pointed to the poor ability of threshold data to predict
      functional abilities for speech in noise (r2 = 0.26 to 0.33) and sound
      localization (r2 = 0.03 to 0.28). Only speech in quiet (r2 = 0.68 to 0.85) is
      predicted adequately from threshold data. CONCLUSIONS: Combined with previous
      findings, results indicate that the use of hearing aids can considerably affect
      F/B localization abilities in a number of individuals. Moreover, speech
      understanding in noise and sound localization abilities were poorly predicted
      from pure-tone thresholds, demonstrating the need to specifically test these
      abilities, both unaided and aided, when assessing AFFD. Finally, further work is
      needed to develop empirically based hearing criteria for the RCMP and identify
      best practices in hearing aid fittings for optimal functional hearing abilities.

PMID- 21864471
TI  - Dichotic and dichoptic digit perception in normal adults.
AB  - BACKGROUND: Verbally based dichotic-listening experiments and reproduction
      mediated response-selection strategies have been used for over four decades to
      study perceptual/cognitive aspects of auditory information processing and make
      inferences about hemispheric asymmetries and language lateralization in the
      brain. Test procedures using dichotic digits have also been used to assess for
      disorders of auditory processing. However, with this application, limitations
      exist and paradigms need to be developed to improve specificity of the diagnosis.
      Use of matched tasks in multiple sensory modalities is a logical approach to
      address this issue. Herein, we use dichotic listening and dichoptic viewing of
      visually presented digits for making this comparison. PURPOSE: To evaluate
      methodological issues involved in using matched tasks of dichotic listening and
      dichoptic viewing in normal adults. RESEARCH DESIGN: A multivariate assessment of
      the effects of modality (auditory vs. visual), digit-span length (1-3 pairs),
      response selection (recognition vs. reproduction), and ear/visual hemifield of
      presentation (left vs. right) on dichotic and dichoptic digit perception. STUDY
      SAMPLE: Thirty adults (12 males, 18 females) ranging in age from 18 to 30 yr with
      normal hearing sensitivity and normal or corrected-to-normal visual acuity. DATA
      COLLECTION AND ANALYSIS: A computerized, custom-designed program was used for all
      data collection and analysis. A four-way repeated measures analysis of variance
      (ANOVA) evaluated the effects of modality, digit-span length, response selection,
      and ear/visual field of presentation. RESULTS: The ANOVA revealed that
      performances on dichotic listening and dichoptic viewing tasks were dependent on
      complex interactions between modality, digit-span length, response selection, and
      ear/visual hemifield of presentation. Correlation analysis suggested a common
      effect on overall accuracy of performance but isolated only an auditory factor
      for a laterality index. CONCLUSIONS: The variables used in this experiment
      affected performances in the auditory modality to a greater extent than in the
      visual modality. The right-ear advantage observed in the dichotic-digits task was
      most evident when reproduction mediated response selection was used in
      conjunction with three-digit pairs. This effect implies that factors such as
      "speech related output mechanisms" and digit-span length (working memory)
      contribute to laterality effects in dichotic listening performance with
      traditional paradigms. Thus, the use of multiple-digit pairs to avoid ceiling
      effects and the application of verbal reproduction as a means of response
      selection may accentuate the role of nonperceptual factors in performance.
      Ideally, tests of perceptual abilities should be relatively free of such effects.

PMID- 21864472
TI  - Diagnostic accuracy of established central auditory processing test batteries in
      patients with documented brain lesions.
AB  - PURPOSE: The sensitivity, specificity, and efficiency of commonly used behavioral
      central auditory processing tests and test batteries were determined for 20
      individuals with known lesions of the central auditory nervous system (CANS) and
      related auditory symptoms. RESEARCH DESIGN: Twenty-nine individuals with no known
      neurological involvement served as the control group. Both groups were
      administered dichotic digits (DD), competing sentences (CS), frequency patterns
      (FP), and low-pass filtered speech (FS) tests. DATA ANALYSIS: Diagnostic indices
      for individual tests and test batteries comprised of two, three, or four tests
      were calculated both using a lax criterion in which failure on only one test in a
      battery led to a positive diagnosis and using a strict criterion in which failure
      on all tests in the battery was necessary to trigger a positive diagnosis.
      RESULTS: The test battery providing the best balance between sensitivity and
      specificity varied as a function of criterion. The two-test DD-FP battery using a
      strict criterion demonstrated the best balance. CONCLUSIONS: Limitations of
      particular tests, the advantages of larger test batteries to more broadly examine
      multiple auditory processes, the degree to which the present results can be
      generalized clinically to populations without known brain lesions, and other
      clinical considerations are discussed.

PMID- 21864473
TI  - Hearing aids in the real world: use of multimemory and volume controls.
AB  - BACKGROUND: Despite advances in technology, hearing aid users continue to express
      a desire for some control over their devices. Access to a suitable control can
      significantly affect overall satisfaction with amplification, yet little is known
      about the circumstances that drive hearing aid users to manipulate controls. Such
      information would be useful in guiding clinical decisions about the selection of
      controls and synchronization of their operation in a bilateral pair of hearing
      aids. PURPOSE: The purpose of this study was to examine the real-world use of
      multimemory (MM) and volume (VC) controls and environmental characteristics that
      may influence their use. RESEARCH DESIGN: Real-time data about MM and VC usage
      were gathered in the real world. Subjective reports of the environmental
      characteristics were obtained. This design allowed examination of the nature of
      hearing aid adjustments as well as exploration of factors affecting them. STUDY
      SAMPLE: Ten adults with bilaterally symmetric, mild-to-moderate sensorineural
      hearing loss participated in the study. All had previous experience with hearing
      aids. INTERVENTION: Participants were fitted bilaterally with BTE (behind-the
      ear) hearing aids equipped with an MM button and/or VC wheel. The devices were
      connected to a PDA (personal digital assistant) that logged data from the hearing
      aids and stored surveys completed by participants in various listening
      situations. DATA COLLECTION AND ANALYSIS: The following data were obtained from
      the PDA: (1) MM and VC settings in the left and right devices, (2) broadband
      input level at the microphone of the left and right devices, and (3) participant
      reports of the presence, distance, and location of signal and background noise.
      Prevalence of nondefault settings and bilateral symmetry of hearing aid
      adjustments were summarized descriptively, while the influence of environmental
      characteristics on hearing aid adjustments was analyzed using nonparametric
      methods. RESULTS: Over 4-5 wk, 912 hr of data were logged and 184 surveys
      completed. Results showed that (1) the default (i.e., the programmed or "use")
      setting was preferred most often, (2) the preferred hearing aid settings were
      mostly bilaterally symmetrical, and (3) nondefault settings were often used in
      difficult listening situations. CONCLUSIONS: The findings of this study generally
      support the use of synchronized MMs and/or VCs, although there may be exceptions
      to their utility.

PMID- 21864474
TI  - Adaptation of the BKB-SIN test for use as a pediatric aided outcome measure.
AB  - BACKGROUND: There is a need for objective pediatric hearing aid outcome
      measurement and thus a need for the evaluation of outcome measures. We explored a
      commercially available pediatric sentence-in-noise measure adapted for use as an
      aided outcome measure. PURPOSE: The purposes of the current study were (1) to
      administer an adapted BKB-SIN (Bamford-Kowal-Bench Speech-in-Noise test) to
      adults and children who have normal hearing and children who use hearing aids and
      (2) to evaluate the utility of this adapted BKB-SIN as an aided, within-subjects
      outcome measure for amplification strategies. RESEARCH DESIGN: We used a mixed
      within and between groups design to evaluate speech recognition in noise for the
      three groups of participants. The children who use hearing aids were tested under
      the omnidirectional, directional, and digital noise reduction (DNR) conditions.
      Results from each group were compared to each other, and we compared results of
      each aided condition for the children who use hearing aids to evaluate the test
      utility as an aided outcome measure. STUDY SAMPLE: The study sample consisted of
      14 adults with normal hearing (aged 22-28 yr) and 15 children with normal hearing
      (aged 6-18 yr), recruited through word of mouth, and 14 children who use hearing
      aids (aged 9-16 yr) recruited from local audiology clinics. DATA COLLECTION AND
      ANALYSIS: List pairs of the BKB-SIN test were presented at 50 dB HL as follows:
      four list pairs to each participant with normal hearing, four list pairs in the
      omnidirectional condition, and two list pairs in the directional and DNR
      conditions. Children who use hearing aids were fitted bilaterally with laboratory
      devices and completed the BKB-SIN test aided. Data were plotted as mean percent
      of key words correct at each signal-to-noise ratio (SNR). Further, we conducted
      an analysis of variance for group differences and within-groups for the three
      aided conditions. RESULTS: Adult participants outperformed children with normal
      hearing, who outperformed the children who use hearing aids. SNR-50 (signal-to
      noise ratio at which listener can obtain a speech recognition score of 50%
      correct) scores demonstrated reliability of the adapted test implementation. The
      BKB-SIN test measured significant differences in performance for omnidirectional
      versus directional microphone conditions but not between omnidirectional and DNR
      conditions. CONCLUSIONS: We conclude that the adapted implementation of the BKB
      SIN test can be administered reliably and feasibly. Further study is warranted to
      develop norms for the adapted implementation as well as to determine if an
      adapted implementation can be sensitive to age effects. Until such norms are
      developed, clinicians should refrain from comparing results from the adapted test
      to the test manual norms and should instead use the adapted implementation as a
      within-subject measure.

PMID- 21864475
TI  - c-Met is a marker of pancreatic cancer stem cells and therapeutic target.
AB  - BACKGROUND & AIMS: Growth of many different tumor types requires a population of
      self-renewing cancer stem cells (CSCs). c-Met is a marker of normal mouse
      pancreatic stem and progenitor cells; we investigated whether it is also a marker
      of human pancreatic CSCs that might be developed as a therapeutic target.
      METHODS: We studied growth of primary human pancreatic adenocarcinoma in NOD SCID
      mice. The self-renewal capability of pancreatic cancer cells that expressed high
      levels of c-Met (c-Met(high)) was assessed using in vitro sphere assays and
      compared with those that were c-Met negative or expressed low levels of c-Met.
      The tumorigenicity of c-Met(high) pancreatic cancer cells was evaluated in NOD
      SCID mice. RESULTS: c-Met(high) cells readily formed spheres, whereas c-Met
      negative cells did not. Use of the c-Met inhibitor XL184 or c-Met knockdown with
      small hairpin RNAs significantly inhibited tumor sphere formation. c-Met(high)
      cells had increased tumorigenic potential in mice; those that expressed c-Met and
      CD44 (0.5%-5% of the pancreatic cancer cells) had the capability for self-renewal
      and the highest tumorigenic potential of all cell populations studied. In
      pancreatic tumors established in NOD SCID mice, c-Met inhibitors slowed tumor
      growth and reduced the population of CSCs when given alone or in combination with
      gemcitabine. Administration of XL184 for 2 weeks after cardiac injection of
      cancer cells prevented the development of metastases. CONCLUSIONS: c-Met is a new
      marker for pancreatic CSCs. It is required for growth and metastasis of
      pancreatic tumors in mice and is a therapeutic target for pancreatic cancer.

PMID- 21864476
TI  - "What color is my parachute": career opportunities in academic gastroenterology
      and hepatology.

PMID- 21864477
TI  - Regenerative medicine and the gut.

PMID- 21864479
TI  - Evaluation of a novel paediatric self-inflating bag to improve accuracy of tidal
      volumes delivered during simulated advanced paediatric resuscitation.
AB  - OBJECTIVE: The aim of the study is to compare the accuracy of manually delivered
      target tidal volumes (TVs) with the conventional paediatric self-inflating bags
      (CPBs) versus the novel paediatric self-inflating bags (NPBs) during simulated
      advanced paediatric resuscitation. METHODS: Before the trial begun, four target
      TV ranges were established using the BroselowTM Tape as a reference: 36-70 ml for
      6-10 kg, 60-105 ml for 10-15 kg, 90-168 ml for 15-24 kg and 144-210 ml for 24-30
      kg. An NPB with four surface marks matching the target TV ranges was prepared.
      Senior medical students (N=73) were enrolled. After 1 week of training in TV
      delivery with both CPB and NPB, subjects participated in a test simulation. Using
      the CPB and NPB in a random cross-over design, participants delivered 10
      ventilations to test lungs connected to gas flow analysers for the randomly
      assigned target TV ranges. RESULTS: Each of the 730 values for TV and peak
      inspiratory pressures (PIPs) delivered by CPB and NPB were analysed. The
      proportion of accurate TV delivery was higher with NPB than with CPB: 84.2%
      versus 45.9% for 36-70 ml, 93.2% versus 42.7% for 60-105 ml, 96.0% versus 70.3%
      for 90-168 ml and 91.2% versus 62.6% for 144-210 ml, respectively (all p<0.0001).
      Compared with NPB, CPB delivery was more varied and was more frequently out of
      range. There were no significant differences in PIP between the CPB and NPB.
      CONCLUSIONS: NPB is useful as a ventilation device for the accurate delivery of
      TV to small children of varying weights.

PMID- 21864478
TI  - Accelerated and progressive and lethal liver fibrosis in mice that lack
      interleukin (IL)-10, IL-12p40, and IL-13Ralpha2.
AB  - BACKGROUND & AIMS: Progressive fibrosis contributes to the morbidity of several
      chronic diseases; it typically develops slowly, so the mechanisms that control
      its progression and resolution have been difficult to model. The proteins
      interleukin (IL)-10, IL-12p40, and IL-13Ralpha2 regulate hepatic fibrosis
      following infection with the helminth parasite Schistosoma mansoni. We examined
      whether these mediators interact to slow the progression of hepatic fibrosis in
      mice with schistosomiasis. METHODS: IL-10(-/-), IL-12/23(p40)(-/-), and IL
      13Ralpha2(-/-) mice were crossed to generate triple knockout (TKO) mice. We
      studied these mice to determine whether the simultaneous deletion of these 3
      negative regulators of the immune response accelerated mortality from liver
      fibrosis following infection with S mansoni. RESULTS: Induction of inflammation
      by S mansoni, liver fibrosis, and mortality increased greatly in TKO mice
      compared with wild-type mice; 100% of the TKO mice died by 10 weeks after
      infection. Morbidity and mortality were associated with the development of portal
      hypertension, hepatosplenomegaly, gastrointestinal bleeding, ascites,
      thrombocytopenia, esophageal and gastric varices, anemia, and increased levels of
      liver enzymes, all features of advanced liver disease. IL-10, IL-12p40, and IL
      13Ralpha2 reduced the production and activity of the profibrotic cytokine IL-13.
      A neutralizing antibody against IL-13 reduced the morbidity and mortality of the
      TKO mice following S mansoni infection. CONCLUSIONS: IL-10, IL-12p40, and IL
      13Ralpha2 act cooperatively to suppress liver fibrosis in mice following
      infection with S mansoni. This model rapidly reproduces many of the complications
      observed in patients with advanced cirrhosis, so it might be used to evaluate the
      efficacy of antifibrotic reagents being developed for schistosomiasis or other
      fibrotic diseases associated with a T-helper 2 cell-mediated immune response.

PMID- 21864480
TI  - Therapeutic hypothermia is associated with improved neurologic outcome and
      survival in cardiac arrest survivors of non-shockable rhythms.
AB  - BACKGROUND: Therapeutic hypothermia improves neurologic outcomes in patients
      resuscitated from cardiac arrest due to ventricular fibrillation. However, its
      role in patients with cardiac arrest due to non-shockable rhythms (pulseless
      electrical activity (PEA) and asystole) is unclear. We hypothesized that
      therapeutic hypothermia favorably impacts neurologic outcome and survival in
      patients resuscitated from cardiac arrest due to non-shockable rhythms. METHODS:
      Retrospectively collected data on consecutive adult patients admitted to Hartford
      Hospital from 1/1/2004 to 11/1/2010 who survived a cardiac arrest due to PEA or
      asystole were analyzed. Patients who underwent therapeutic hypothermia (1/1/2007
      11/1/2010) formed the hypothermia group while patients admitted prior to the
      institution of therapeutic hypothermia (1/1/2004-1/1/2007) at Hartford Hospital
      formed the control group. The primary end-point was measured using the Pittsburgh
      cerebral performance category (CPC) scale and patients were assessed for a good
      (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from
      hospital. A secondary end-point was measured as survival at discharge from
      hospital. RESULTS: Of 100 post-cardiac arrest patients included in the study,
      15/52 (29%) patients in the hypothermia group had a good neurologic outcome as
      compared to 5/43 (10%) patients in the control group (P=0.021). On multivariate
      analysis, the odds ratio for good neurologic outcome and survival at discharge
      from the hospital with therapeutic hypothermia as compared to control were 4.35
      (95% CI 1.10-17.24, P=0.04) and 5.65 (CI 1.66-19.23, P=0.006) respectively.
      CONCLUSION: Therapeutic hypothermia is associated with favorable neurologic
      outcome and survival in patients resuscitated after cardiac arrest due to non
      shockable rhythms.

PMID- 21864481
TI  - Wasted breath: dispatcher-assisted CPR in out-of-hospital cardiac arrest meets
      cardio-cerebral resuscitation.

PMID- 21864482
TI  - Circulating cell-free DNA levels correlate with postresuscitation survival rates
      in out-of-hospital cardiac arrest patients.
AB  - Early prediction of prognosis is helpful in cardiac arrest patients. Plasma cell
      free DNA, which increases rapidly after cell death, is a novel biomarker for the
      prognosis of critical ill patients. Changes in the plasma cell-free DNA level and
      its role for the early prognosis of cardiac arrest patients remain unclear. We
      prospectively enrolled adult out-of-hospital cardiac arrest (OHCA) patients with
      sustained return of spontaneous circulation. The resuscitation variables were
      recorded following the Utstein recommendation. The plasma cell-free DNA
      concentration was determined by quantitative real-time polymerase chain reaction
      assay of beta-globin gene. A total of 42 patients were enrolled for the study.
      The plasma cell-free DNA level within 2h after cardiac arrest was higher in the
      non-survival group than the survival-to-discharge group (median level 1659.9
      g.e./mL vs. 1121.6g.e./mL, p=0.003 by non-parametric test). The plasma cell-free
      DNA level at 72 h became no difference between these two groups. The optimal
      cutoff value of plasma cell-free DNA for predicting survival-to-discharge was
      1,170 g.e./mL by ROC curve analysis (area under curve 0.752, p=0.010). A plasma
      cell-free DNA level higher than 1,170 g.e./mL and was an independent predictor
      for in-hospital mortality by multiple logistic regression analysis (adjusted odds
      ratio of 12.35, p=0.023) and was also associated with higher 90 day mortality
      (p=0.021 by log-rank test). In conclusion, the plasma cell-free DNA level
      increases during the early post-cardiac arrest phase and can be an early
      prognostic factor for OHCA patients.

PMID- 21864483
TI  - Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves
      vital organ perfusion pressures and carotid blood flow in a porcine model of
      cardiac arrest.
AB  - PURPOSE OF THE STUDY: To describe a new method of CPR that optimizes vital organ
      perfusion pressures and carotid blood flow. We tested the hypothesis that a
      combination of high dose sodium nitroprusside (SNP) as well as non-invasive
      devices and techniques known independently to enhance circulation would
      significantly improve carotid blood flow (CBF) and return of spontaneous
      circulation (ROSC) rates in a porcine model of cardiac arrest. METHODS: 15
      isofluorane anesthetized pigs (30+/-1 kg), after 6 min of untreated ventricular
      fibrillation, were subsequently randomized to receive either 15 min of standard
      CPR (S-CPR) (8 animals) or 5 min epochs of S-CPR followed by active compression
      decompression (ACD)+inspiratory impedance threshold device (ITD) CPR followed by
      ACD+ITD+abdominal binding (AB) with 1mg of SNP administered at minutes 2, 7, 12
      of CPR (7 animals). Primary endpoints were CBF and ROSC rates. ANOVA and Fisher's
      exact test were used for comparisons. RESULTS/CONCLUSION: There was significant
      improvement in the hemodynamic parameters in the SNP animals. ROSC was achieved
      in 7/7 animals that received SNP and in 2/8 in the S-CPR (p=0.007). CBF and end
      tidal CO(2) (ETCO(2)) were significantly higher in the ACD+ITD+AB+SNP (SNPeCPR)
      animals during CPR. Bolus doses of SNP, when used in conjunction with ACD+ITD+AB
      CPR, significantly improve CBF and ROSC rates compared to S-CPR.

PMID- 21864484
TI  - Treatment with beta-hydroxybutyrate and melatonin is associated with improved
      survival in a porcine model of hemorrhagic shock.
AB  - INTRODUCTION: The neuroprotective ketone beta-hydroxybutyrate (BHB) and the
      antioxidant melatonin have been found at elevated levels in hibernating mammals.
      Previous studies in rat models of hemorrhagic shock have suggested a benefit. We
      compared infusion of 4M BHB and 43 mM melatonin (BHB/M) to 4M sodium chloride and
      20% DMSO (control solution) to evaluate for potential benefits in porcine
      hemorrhagic shock. METHODS: Hemorrhagic shock was induced to obtain systolic
      blood pressures <50 mmHg for 60 min. Pigs were treated with a bolus of either
      BHB/M (n=9) or control solution (n=8) followed by 4-h infusion of the either
      BHB/M or control solution. All animals were then resuscitated for 20 h after
      shock. Physiological data were continually recorded, and blood samples were taken
      at intervals throughout the experiment. Serum samples were analyzed via high
      resolution NMR for metabolomic response. RESULTS: BHB/M treatment significantly
      increased 24-h survival time when compared to treatment with control solution
      (100% versus 62%; p=0.050), with a trend toward decreased volume of resuscitative
      fluid administered to animals receiving BHB/M. BHB/M-treated animals had lower
      base deficit and higher oxygen consumption when compared to animals receiving
      control solution. Serum metabolite profiles revealed increases in beta
      hydroxybutyrate (BHB), succinate, 2-oxovalerate and adipate with BHB/M treatment
      as compared with animals treated with control infusion. CONCLUSION: Infusion of
      BHB/M conferred a survival benefit over infusion of control solution in
      hemorrhagic shock. BHB and its products of metabolism are identified in serum of
      animals subjected to shock and treated with BHB/M. Further preclinical studies
      are needed to clarify the mechanisms of action of this promising treatment
      strategy.

PMID- 21864485
TI  - P-selectin glycoprotein ligand-1 positive microparticles in allogeneic stem cell
      transplantation of hematologic malignancies.
AB  - P-selectin and its receptor P-selectin glycoprotein ligand-1 (PSGL-1) mediate
      adhesion between leukocytes, tumor cells (including leukemias and lymphomas), and
      platelets, and play an important role in hematopoiesis, T cell activation, and
      cancer growth and metastasis. As microparticles (MPs) are released from activated
      or apoptotic cells, there should be significant numbers of circulating PSGL-1
      bearing MPs in the blood of patients undergoing allogeneic stem cell
      transplantation (alloSCT). We enumerated PSGL-1-expressing MPs in plasma samples
      from 30 consecutive patients with hematologic disorders at different time points
      during the course of alloSCT by flow cytometry and analyzed their relation to
      cell counts, patient characteristics, and clinical outcome. Median follow-up time
      of surviving patients was 1,772 days (range 1272-1981 days). Nineteen patients
      (63.3%) died, 10 due to progression of disease (33.3%). The PSGL-1 MPs
      significantly declined during conditioning therapy but increased again after
      transfusion of donor cells and even more at the time of engraftment. Numbers
      >250/MUL after graft transfusion were associated with a shorter time to
      engraftment for patients receiving fresh peripheral stem cell grafts (median, 15
      vs. 21 days; p = 0.049). Furthermore, low PSGL-1 MP values at those two time
      points were associated with a higher risk of progress/relapse in univariate
      analysis (p = 0.008-0.014; hazard ratio [HR] = 15.0-42.0) with cumulative
      incidences at 5 years of 81.8% versus 28.6% and 85.7% versus 20.0%, respectively.
      In conclusion, PSGL-1 microparticles show a characteristic course during alloSCT
      and their possible association with relapse/progress requires further evaluation
      of the PSGL-1/P-selectin interaction in leukemias and lymphomas.

PMID- 21864486
TI  - Interleukin-15 enhances rituximab-dependent cytotoxicity against chronic
      lymphocytic leukemia cells and overcomes transforming growth factor beta-mediated
      immunosuppression.
AB  - Chemoimmunotherapy with anti-CD20 monoclonal antibody rituximab is increasingly
      used for the treatment of patients with chronic lymphocytic leukemia (CLL).
      Antibody-dependent cytotoxicity (ADCC) is one of the most important mechanisms of
      action of rituximab against B-cell malignancies. We studied ways to increase the
      cytotoxic effect of rituximab on CLL cells by enhancing ADCC. Peripheral blood
      mononuclear cell (PBMC) or purified natural killer (NK) cells from healthy donors
      were activated with interleukin-15 (IL-15) and cultured with rituximab-coated CLL
      cells, and ADCC was evaluated using a (51)chromium release assay. The IL-15
      significantly enhanced in vitro ADCC against CLL cells, and this effect was
      mainly mediated by NK cells. The IL-15 treated effector cells with the low
      affinity FcgammaRIIIA receptor (158FF) had an ADCC comparable to those with the
      high affinity FcgammaRIIIA form (158VF). In addition, IL-15 enhanced rituximab
      mediated ADCC of CLL cells in the presence of transforming growth factor-beta.
      The IL-15 increases rituximab-mediated ADCC against CLL, and supports the use of
      such agents with the goal of improving clinical response to chemoimmunotherapy in
      patients with CLL.

PMID- 21864487
TI  - Isolation strategies of regulatory T cells for clinical trials: phenotype,
      function, stability, and expansion capacity.
AB  - Recent clinical results demonstrate the highly effective potency of regulatory T
      cells (Tregs) to control graft-versus-host disease (GvHD). In this presented
      study, we directly compared different Treg subpopulations in order to define the
      most promising Treg target cell population for cellular intervention studies with
      respect to their phenotype, functional properties, stability, and expansion
      capacity. Different Treg cell populations have been isolated from healthy donors
      and characterized by fluorescence activated cell sorting (FACS) analysis for
      their phenotypic marker and purity, functional properties by suppression assay,
      stability by Treg-specific demethylated region (TSDR) of the Foxp3 promoter and
      their in vitro expansion capacity. The direct comparison of the respective Treg
      target cell populations identified CD4(+)CD25(hi)CD127(-) and
      CD4(+)CD25(hi)ICOS(+) Tregs as the most promising Treg population for fresh cell
      infusions in clinical trials with respect to cell yield, phenotype, function, and
      stability. The CD4(+)CD25(hi) Tregs qualified as the best candidate for in vitro
      expansion combining a highly stable phenotype with strong suppressive potential
      and attractive cell yield after repetitive stimulation. The suppressive capacity
      of freshly isolated CD4(+)CD25(hi)CD45RA(+) and CD49d(-)CD127(-) Tregs is
      comparable to freshly isolated CD4(+)CD25(hi), but inferior to
      CD4(+)CD25(hi)CD127(-) and CD4(+)CD25(hi)ICOS(+) Tregs. In vitro expansion of
      CD4(+)CD25(hi)CD45RA(+) and CD49d(-)CD127(-) Tregs resulted in cell populations
      with less suppressive potency compared with CD4(+)CD25(hi) expanded Tregs
      correlating well with a higher TSDR demethylation level. In conclusion, future
      clinical trials should favor CD4(+)CD25(hi)CD127(-) and CD4(+)CD25(hi)ICOS(+)
      Tregs for direct Treg cell transfer, whereas CD4(+)CD25(hi) Tregs qualify as best
      candidate for in vitro expansion.

PMID- 21864488
TI  - Marrow cell genetic phenotype change induced by human lung cancer cells.
AB  - Microvesicles have been shown to mediate varieties of intercellular
      communication. Work in murine species has shown that lung-derived microvesicles
      can deliver mRNA, transcription factors, and microRNA to marrow cells and alter
      their phenotype. The present studies evaluated the capacity of excised human lung
      cancer cells to change the genetic phenotype of human marrow cells. We present
      the first studies on microvesicle production by excised cancers from human lung
      and the capacity of these microvesicles to alter the genetic phenotype of normal
      human marrow cells. We studied 12 cancers involving the lung and assessed nine
      lung-specific mRNA species (aquaporin, surfactant families, and clara cell
      specific protein) in marrow cells exposed to tissue in co-culture, cultured in
      conditioned media, or exposed to isolated lung cancer-derived microvesicles. We
      assessed two or seven days of co-culture and marrow which was unseparated,
      separated by ficoll density gradient centrifugation or ammonium chloride lysis.
      Under these varying conditions, each cancer derived from lung mediated marrow
      expression of between one and seven lung-specific genes. Microvesicles were
      identified in the pellet of ultracentrifuged conditioned media and shown to enter
      marrow cells and induce lung-specific mRNA expression in marrow. A lung melanoma
      and a sarcoma also induced lung-specific mRNA in marrow cells. These data
      indicate that lung cancer cells may alter the genetic phenotype of normal cells
      and suggest that such perturbations might play a role in tumor progression, tumor
      recurrence, or metastases. They also suggest that the tissue environment may
      alter cancer cell gene expression.

PMID- 21864489
TI  - The aging effect of chemotherapy on cultured human mesenchymal stem cells.
AB  - Various agents, including chemotherapeutic drugs, can induce cell senescence.
      However, the mechanisms involved in the aging pathway, particularly the stress
      that chemotherapy imposes on telomeres, are still undefined. To address these
      issues, human mesenchymal stem cells (MSCs) were assessed as target cells to
      investigate the initiation of the aging process by chemotherapy. The MSCs were
      obtained from bone marrow (BM) cells from normal adults and grown in the presence
      of platelet lysates. Cultured MSCs were identified for immunophenotype, and for
      growth and differentiation properties. The MSCs were exposed to 10 nM doxorubicin
      and 500 ng/mL etoposide, sublethal doses that induce DNA double-stranded breaks.
      Telomere length (TL) was assessed by flow-fluorescence in situ hybridization and
      Southern blotting. Initial TL shortening was detectable in MSCs at 5 days after
      drug exposure, with progressive reduction compared with untreated cells at 7, 14,
      21, and 28 days in culture. After a single exposure, MSCs were unable to regain
      the lost telomere sequences for up to 28 days in culture. The ATM phosphorylation
      was documented early after drug exposure, while no telomerase activation was
      observed. Chemotherapy-induced TL shortening was associated with reduced
      clonogenic activity in vitro and accelerated adipose differentiation. Analogous
      behavior in the differentiation pattern was observed in naturally aged MSCs.
      These results indicate that cultured MSCs represent a useful cellular model to
      investigate novel drugs that may favor or, conversely, might prevent TL loss in
      human stem cells. The TL shortening is a permanent signature of previous
      chemotherapy-mediated DNA damage, and predicts impaired proliferative and
      differentiation potential.

PMID- 21864490
TI  - Nanoparticle augmented radiation treatment decreases cancer cell proliferation.
AB  - We report significant and controlled cell death using novel x-ray-activatable
      titania nanoparticles (NPs) doped with lanthanides. Preferential incorporation of
      such materials into tumor tissue can enhance the effect of radiation therapy.
      Herein, the incorporation of gadolinium into the NPs is designed to optimize
      localized energy absorption from a conventional medical x-ray. This result is
      further optimized by the addition of other rare earth elements. Upon irradiation,
      energy is transferred to the titania crystal structure, resulting in the
      generation of reactive oxygen species (ROS). FROM THE CLINICAL EDITOR: The
      authors report significant and controlled cell death using x-ray-activated
      titania nanoparticles doped with lanthanides as enhancers. Upon irradiation X-ray
      energy is transferred to the titania crystal structure, resulting in the
      generation of reactive oxygen species.

PMID- 21864491
TI  - The extent of desmoglein 3 depletion in pemphigus vulgaris is dependent on Ca(2+)
      induced differentiation: a role in suprabasal epidermal skin splitting?
AB  - Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes
      and is characterized by development of autoantibodies against the desmosomal
      cadherins desmoglein (Dsg) 3 and Dsg1 and formation of intraepidermal suprabasal
      blisters. Depletion of Dsg3 is a critical mechanism in PV pathogenesis. Because
      we did not detect reduced Dsg3 levels in keratinocytes cultured for longer
      periods under high-Ca(2+) conditions, we hypothesized that Dsg depletion depends
      on Ca(2+)-mediated keratinocyte differentiation. Our data indicate that depletion
      of Dsg3 occurs specifically in deep epidermal layers both in skin of patients
      with PV and in an organotypic raft model of human epidermis incubated using IgG
      fractions from patients with PV. In addition, Dsg3 depletion and loss of Dsg3
      staining were prominent in cultured primary keratinocytes and in HaCaT cells
      incubated in high-Ca(2+) medium for 3 days, but were less pronounced in HaCaT
      cultures after 8 days. These effects were dependent on protein kinase C signaling
      because inhibition of protein kinase C blunted both Dsg3 depletion and loss of
      intercellular adhesion. Moreover, protein kinase C inhibition blocked suprabasal
      Dsg3 depletion in cultured human epidermis and blister formation in a neonatal
      mouse model. Considered together, our data indicate a contribution of Dsg
      depletion to PV pathogenesis dependent on Ca(2+)-induced differentiation.
      Furthermore, prominent depletion in basal epidermal layers may contribute to the
      suprabasal cleavage plane observed in PV.

PMID- 21864492
TI  - Signal transducer and activator of transcription 3 (Stat3C) promotes myeloid
      derived suppressor cell expansion and immune suppression during lung
      tumorigenesis.
AB  - Signal transducer and activator of transcription 3 (Stat3) is a potent
      transcription factor with diverse biological functions. Overexpression of
      constitutively active form Stat3C in lung alveolar type II (AT II) epithelial
      cells in CCSP-rtTA/(tetO)(7)-CMV-Stat3C bitransgenic mice induces chronic
      inflammation and lung bronchioalveolar adenocarcinoma. In the present study, the
      population of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) was
      significantly increased in lung and blood of doxycycline-treated bitransgenic
      mice, but CD4(+) and CD8(+) T cells were decreased. In bronchioalveolar lavage
      fluid and plasma of doxycycline-treated bitransgenic mice, concentrations of MDSC
      stimulating cytokines IL-1beta, IL-6, IL-10, IL-13, INF-gamma, TNF-alpha, and GM
      CSF were significantly increased, which stimulated alveolar monocytes/macrophages
      to CD11b(+)Gr-1(+) cell conversion in vitro. Phosphorylation of proto-oncogenic
      intracellular signaling molecules Stat3, Erk1/2, and P38 was significantly
      increased in CD11b(+)Gr-1(+) cells from lung and blood of doxycycline-treated
      bitransgenic mice. CD11b(+)Gr-1(+) cells from lung of doxycycline-treated
      bitransgenic mice strongly inhibited proliferation and function of wild-type
      CD4(+) T cells in vitro. These findings support the concept that persistent
      activation of Stat3 induces inflammation during lung cancer by promoting MDSC
      mediated immune suppression.

PMID- 21864493
TI  - A novel type of macrothrombocytopenia associated with a defect in alpha2,3
      sialylation.
AB  - We describe a novel type of human thrombocytopenia characterized by the
      appearance of giant platelets and variable neutropenia. Searching for the
      molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X
      and increased Lewis X surface expression, pointing to a deficiency in
      sialylation. We show that the glycosylation defect is restricted to alpha2,3
      sialylation and can be detected in platelets, neutrophils, and monocytes.
      Platelets exhibited a distorted structure of the open canalicular system,
      indicating defective platelet generation. Importantly, patient platelets, but not
      normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell
      surface protein that removes desialylated thrombocytes from the circulation in
      mice. Taken together, this is the first type of human thrombocytopenia in which a
      specific defect of alpha2,3-sialylation and an induction of platelet binding to
      the liver ASGP-R could be detected.

PMID- 21864494
TI  - Measurement of cystic fibrosis transmembrane conductance regulator activity using
      fluorescence spectrophotometry.
AB  - Cystic fibrosis (CF) is a frequent autosomal recessive disease caused by
      mutations that impair the CF transmembrane conductance regulator (CFTR) protein
      function. CFTR is a chloride channel activated by cyclic AMP (cAMP) via protein
      kinase A (PKA) and ATP hydrolysis. We describe here a method to measure CFTR
      activity in a monolayer of cultured cells using a fluorescence spectrophotometer
      and the chloride-sensitive probe 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ).
      Modifying a slice holder, the spectrophotometer quartz cuvette was converted in a
      perfusion chamber, allowing measurement of CFTR activity in real time, in a
      monolayer of T84 colon carcinoma cells. The SPQ Stern-Volmer constant (K(Cl(-)))
      for chloride in water solution was 115.0 +/- 2.8M(-1), whereas the intracellular
      (K(Cl(-))) was 17.8 +/- 0.8 M(-1), for T84 cells. A functional analysis was
      performed by measuring CFTR activity in T84 cells. The CFTR transport inhibitors
      CFTR(inh)-172 (5 MUM) and glibenclamide (100 MUM) showed a significant reduction
      (P<0.05) in CFTR activity. This simple method allows measuring CFTR activity in a
      very simple, reproducible, and sensitive way.

PMID- 21864495
TI  - Electrochemical titrations and reaction time courses monitored in situ by
      magnetic circular dichroism spectroscopy.
AB  - Magnetic circular dichroism (MCD) spectra, at ultraviolet-visible or near
      infrared wavelengths (185-2000 nm), contain the same transitions observed in
      conventional absorbance spectroscopy, but their bisignate nature and more
      stringent selection rules provide greatly enhanced resolution. Thus, they have
      proved to be invaluable in the study of many transition metal-containing
      proteins. For mainly technical reasons, MCD has been limited almost exclusively
      to the measurement of static samples. But the ability to employ the resolving
      power of MCD to follow changes at transition metal sites would be a potentially
      significant advance. We describe here the development of a cuvette holder that
      allows reagent injection and sample mixing within the 50-mm-diameter ambient
      temperature bore of an energized superconducting solenoid. This has allowed us,
      for the first time, to monitor time-resolved MCD resulting from in situ chemical
      manipulation of a metalloprotein sample. Furthermore, we report the parallel
      development of an electrochemical cell using a three-electrode configuration with
      physically separated working and counter electrodes, allowing true potentiometric
      titration to be performed within the bore of the MCD solenoid.

PMID- 21864497
TI  - Real-time monitoring of matrix metalloproteinase-9 collagenolytic activity with a
      surface plasmon resonance biosensor.
AB  - We describe a simple method for real-time monitoring of matrix metalloproteinase
      9 (MMP-9) collagenolytic activity for native triple helical collagen IV with a
      surface plasmon resonance (SPR) biosensor. The proteolytic activity of MMP-9 is
      measured as a decrease in the SPR signal resulting from the cleavage of collagen
      IV immobilized on the sensor surface. The kinetic parameters of full-length MMP-9
      and its catalytic domain-catalytic constant (k(cat)), association rate constant
      (k(a)), and dissociation rate constant (k(d))-were estimated by the SPR method.
      The presence of sodium chloride and a nonionic detergent Brij-35 in a reaction
      solution led to the lower collagenolytic activity of MMP-9, whereas they
      suppressed the nonspecific interaction between MMP-9 and a cysteamine-modified
      chip. The comparison of kinetic parameters between MMP-9 and its catalytic domain
      revealed that the association constant of MMP-9 is much larger than that of the
      catalytic domain, suggesting that the interplay among hemopexin-like domain,
      fibronectin type II repeats motif, and linker region (O-glycosylated domain)
      plays an important role in recognizing collagen IV.

PMID- 21864496
TI  - A viability assay for Candida albicans based on the electron transfer mediator
      2,6-dichlorophenolindophenol.
AB  - Candida albicans is an opportunistic fungal pathogen with comparably high
      respiratory activity. Thus, we established a viability test based on 2,6
      dichlorophenolindophenol (DCIP), a membrane-permeable electron transfer agent.
      NADH dehydrogenases catalyze the reduction of DCIP by NADH, and the enzymatic
      activity can be determined either electrochemically via oxidation reactions of
      DCIP or photometrically. Among the specific respiratory chain inhibitors, only
      the complex I inhibitor rotenone decreased the DCIP signal from C. albicans,
      leaving residual activity of approximately 30%. Thus, the DCIP-reducing activity
      of C. albicans was largely dependent on complex I activity. C. albicans is
      closely related to the complex I-negative yeast Saccharomyces cerevisiae, which
      had previously been used in DCIP viability assays. Via comparative studies, in
      which we included the pathogenic complex I-negative yeast Candida glabrata, we
      could define assay conditions that allow a distinction of complex I-negative and 
      positive organisms. Basal levels of DCIP turnover by S.cerevisiae and C. glabrata
      were only 30% of those obtained from C. albicans but could be increased to the C.
      albicans level by adding glucose. No significant increases were observed with
      galactose. DCIP reduction rates from C. albicans were not further increased by
      any carbon source.

PMID- 21864498
TI  - Protein chip for the parallel quantification of high and low abundant biomarkers
      for sepsis.
AB  - We present herein a protein chip for diagnosis of sepsis that combines both a
      sandwich and a binding inhibition format in order to quantify high (CRP) and low
      abundant proteins (cytokines, PCT, neopterin) in parallel. Using the combined
      assay format the lowest detectable concentrations for CRP, IL-6, IL-8, IL-10,
      TNFalpha, PCT, and neopterin are 3 mg/L, 15 ng/L, 26 ng/L, 65 ng/L, 40 ng/L, 78
      ng/L, and 0.46 MUg/L. Four different combined assay formats are tested, using
      separate or joint incubation steps of analytes and detection antibodies. Yet, low
      limit of detection (LOD) and short processing time are contradictory: while the
      combined assay performed in a multistep protocol is extremely sensitive (e.g.,
      the LOD for IL-6 is 15 ng/L), but more time-consuming (4 h), the all-in-one
      protocol takes only 2.5 h, but suffers from lower sensitivity compared with the
      multistep protocol (e.g., the LOD for IL-6 is up to 40 times enhanced).
      Reproducibility is good in both cases (CV 5-20%).

PMID- 21864499
TI  - Regioselective oxygenation of fatty acids, fatty alcohols and other aliphatic
      compounds by a basidiomycete heme-thiolate peroxidase.
AB  - Reaction of fatty acids, fatty alcohols, alkanes, sterols, sterol esters and
      triglycerides with the so-called aromatic peroxygenase from Agrocybe aegerita was
      investigated using GC-MS. Regioselective hydroxylation of C(12)-C(20)
      saturated/unsaturated fatty acids was observed at the omega-1 and omega-2
      positions (except myristoleic acid only forming the omega-2 derivative). Minor
      hydroxylation at omega and omega-3 to omega-5 positions was also observed.
      Further oxidized products were detected, including keto, dihydroxylated, keto
      hydroxy and dicarboxylic fatty acids. Fatty alcohols also yielded hydroxy or keto
      derivatives of the corresponding fatty acid. Finally, alkanes gave, in addition
      to alcohols at positions 2 or 3, dihydroxylated derivatives at both sides of the
      molecule; and sterols showed side-chain hydroxylation. No derivatives were found
      for fatty acids esterified with sterols or forming triglycerides, but methyl
      esters were omega-1 or omega-2 hydroxylated. Reactions using H(2)(18)O(2)
      established that peroxide is the source of the oxygen introduced in aliphatic
      hydroxylations. These studies also indicated that oxidation of alcohols to
      carbonyl and carboxyl groups is produced by successive hydroxylations combined
      with one dehydration step. We conclude that the A. aegerita peroxygenase not only
      oxidizes aromatic compounds but also catalyzes the stepwise oxidation of
      aliphatic compounds by hydrogen peroxide, with different hydroxylated
      intermediates.

PMID- 21864500
TI  - Kinetic and spectroscopic characterization of the putative monooxygenase domain
      of human MICAL-1.
AB  - MICALs form a conserved multidomain protein family essential for cytoskeletal
      rearrangements. To complement structural information available, we produced the
      FAD-containing monooxygenase-like domain of human MICAL-1 (MICAL-MO) in forms
      differing for the presence and location of a His-tag, which only influences the
      protein yields. The K(m) for NADPH of the NADPH oxidase reaction is sensitive to
      ionic strength and type of ions. The apparent k(cat) (pH 7) is limited by enzyme
      reduction by NADPH, which occurs without detectable intermediates, as established
      by anaerobic rapid reaction experiments. The sensitivity to ionic strength and
      type of ions and the pH dependence of the steady-state kinetic parameters extend
      MICAL-MO similarity with enzymes of the p-hydroxybenzoate hydroxylase class at
      the functional level. The reaction is also sensitive to solvent viscosity,
      providing a tool to monitor the conformational changes predicted to occur during
      turnover. Finally, it was confirmed that MICAL-MO promotes actin
      depolymerization, and it was shown that F-actin, but not G-actin, stimulates
      NADPH oxidation by increasing k(cat) and k(cat)/K(NADPH) (~5 and ~200-fold,
      respectively) with an apparent K(m) for actin of 4.7MUM, under conditions that
      stabilize F-actin. The time-course of NADPH oxidation shows substrate recycling,
      indicating the possible reversibility of MICAL effect.

PMID- 21864501
TI  - Cytochrome b559 and cyclic electron transfer within photosystem II.
AB  - Cytochrome b559 (Cyt b559), beta-carotene (Car), and chlorophyll (Chl) cofactors
      participate in the secondary electron-transfer pathways in photosystem II (PSII),
      which are believed to protect PSII from photodamage under conditions in which the
      primary electron-donation pathway leading to water oxidation is inhibited. Among
      these cofactors, Cyt b559 is preferentially photooxidized under conditions in
      which the primary electron-donation pathway is blocked. When Cyt b559 is
      preoxidized, the photooxidation of several of the 11 Car and 35 Chl molecules
      present per PSII is observed. In this review, the discovery of the secondary
      electron donors, their structures and electron-transfer properties, and progress
      in the characterization of the secondary electron-transfer pathways are
      discussed. This article is part of a Special Issue entitled: Photosystem II.

PMID- 21864502
TI  - Fluorescence spectroscopy studies of HEK293 cells expressing DOR-Gi1alpha fusion
      protein; the effect of cholesterol depletion.
AB  - Biophysical studies of fluorescence anisotropy of DPH and Laurdan generalized
      polarization were performed in plasma membranes (PM) isolated from control and
      cholesterol-depleted HEK293 cells stably expressing pertussis toxin (PTX)
      insensitive DOR-Gi1alpha (Cys351-Ile351) fusion protein. PM isolated from
      control, PTX-untreated, cells were compared with PM isolated from PTX-treated
      cells. Results from both types of PM indicated that i) hydrophobic membrane
      interior was made more accessible to water molecules and more chaotically
      organized in cholesterol-depleted samples, ii) cholesterol depletion resulted in
      an overall increase in surface area of membrane, membrane fluidity, and mobility
      of its constituents. Analysis of DOR-Gi1alpha coupling in PTX-treated and PTX
      untreated cells indicated that cholesterol depletion did not alter the agonist
      binding site of DOR (Bmax and Kd) but the ability of DOR agonist DADLE to
      activate G proteins was markedly impaired. In PTX-untreated membranes, EC50 for
      DADLE-stimulated [35S]GTPgammaS binding was shifted by one order of magnitude to
      the right: from 4.3+/-1.2*10(-9) M to 2.2+/-1.3*10(-8) M in control and
      cholesterol-depleted membrane samples, respectively. In PTX-treated membranes,
      EC50 was shifted from 4.5+/-1.1*10(-9) M to 2.8+/-1.4*10(-8) M. In summary, the
      perturbation of optimum PM organization by cholesterol depletion deteriorates
      functional coupling of DOR to covalently bound Gi1alpha as well as endogenously
      expressed PTX-sensitive G proteins of Gi/Go family while receptor ligand binding
      site is unchanged. The biophysical state of hydrophobic plasma (cell) membrane
      interior should be regarded as regulatory factor of DOR-signaling cascade.

PMID- 21864503
TI  - The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular
      accumulation of zinc.
AB  - TRPC6 are plasma membrane cation channels. By means of live-cell imaging and
      spectroscopic methods, we found that HEK cells expressing TRPC6 channels (HEK
      TRPC6) are enriched in zinc and sulphur and have a reduced copper content when
      compared to HEK cells and HEK cells expressing TRPC3 channels (HEK-TRPC3). Hence,
      HEK-TRPC6 cells have larger pools of mobilizable Zn2+ and are more sensitive to
      an oxidative stress. Synchrotron X-ray fluorescence experiments showed a higher
      zinc content in the nuclear region indicating that the intracellular distribution
      of this metal was influenced by the over-expression of TRPC6 channels. Their
      properties were investigated with the diacylglycerol analogue SAG and the plant
      extract hyperforin. Electrophysiological recordings and imaging experiments with
      the fluorescent Zn2+ probe FluoZin-3 demonstrated that TRPC6 channels form Zn2+
      conducting channels. In cortical neurons, hyperforin-sensitive channels co-exist
      with voltage-gated channels, AMPA and NMDA receptors, which are known to
      transport Zn2+. The ability of these channels to regulate the size of the
      mobilizable pools of Zn2+ was compared. The data collected indicate that the
      entry of Zn2+ through TRPC6 channels can up-regulate the size of the DTDP
      sensitive pool of Zn2+. By showing that TRPC6 channels constitute a Zn2+ entry
      pathway, our study suggests that they could play a role in zinc homeostasis.

PMID- 21864504
TI  - The natural antioxidant rosmarinic acid spontaneously penetrates membranes to
      inhibit lipid peroxidation in situ.
AB  - Exogenous molecules from dietary sources such as polyphenols are very efficient
      in preventing the alteration of lipid membranes by oxidative stress. Among the
      polyphenols, we have chosen to study rosmarinic acid (RA). We investigated the
      efficiency of RA in preventing lipid peroxidation and in interacting with lipids.
      We used liposomes of 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) to show
      that RA was an efficient antioxidant. By HPLC, we determined that the maximum
      amount of RA associated with the lipids was ~1 mol%. Moreover, by using Langmuir
      monolayers, we evidenced that cholesterol decreases the penetration of RA. The
      investigation of transferred lipid/RA monolayers by atomic force microscopy
      revealed that 1 mol% of RA in the membrane was not sufficient to alter the
      membrane structure at the nanoscale. By fluorescence, we observed no significant
      modification of membrane permeability and fluidity caused by the interaction with
      RA. We also deduced that RA molecules were mainly located among the polar
      headgroups of the lipids. Finally, we prepared DLPC/RA vesicles to evidence for
      the first time that up to 1 mol% of RA inserts spontaneously in the membrane,
      which is high enough to fully prevent lipid peroxidation without any noticeable
      alteration of the membrane structure due to RA insertion.

PMID- 21864505
TI  - A novel splicing variant of CADM2 as a protective transcript of psoriasis.
AB  - CADM2, a candidate gene for psoriasis, was identified by a genome-wide
      association study using microsatellites in the Japanese population (561 cases and
      561 controls). Moreover, haplotype analysis included an additional 68 SNPs and
      indicated that a 110-kb haplotype block was detected for the protective risk
      haplotype of psoriasis. We also identified an initial exon of novel splicing
      variants in this haplotype block. A functional analysis by qRT-PCR using RNAs
      from the blood of 56 cases and 64 controls significantly demonstrated an inverse
      correlation between expression frequencies in a novel splicing variant and the
      number of alleles associated with psoriasis. To confirm these results, we must
      perform replication studies using other ethnic groups and more functional
      analysis particularly for skin tissues.

PMID- 21864506
TI  - Targeting microRNAs involved in human diseases: a novel approach for modification
      of gene expression and drug development.
AB  - The identification of all epigenetic modifications (i.e. DNA methylation, histone
      modifications and expression of noncoding RNAs such as microRNAs) involved in
      gene regulation is one of the major steps forward for understanding human biology
      in both normal and pathological conditions and for development of novel drugs. In
      this context, microRNAs play a pivotal role. This review article focuses on the
      involvement of microRNAs in the regulation of gene expression, on the possible
      role of microRNAs in the onset and development of human pathologies, and on the
      pharmacological alteration of the biological activity of microRNAs. RNA and DNA
      analogs, which can selectively target microRNAs using Watson-Crick base pairing
      schemes, provide a rational and efficient way to modulate gene expression. These
      compounds, termed antago-miR or anti-miR have been described in many examples in
      the recent literature and have proved to be able to perform regulatory as well as
      therapeutic functions. Among these, a still not fully exploited class is that of
      peptide nucleic acids (PNAs), promising tools for the inhibition of miRNA
      activity, with important applications in gene therapy and in drug development.
      PNAs targeting miR-122, miR-155 and miR-210 have already been developed and their
      biological effects studied both in vitro and in vivo.

PMID- 21864507
TI  - Underexpression of miR-224 in methotrexate resistant human colon cancer cells.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs involved in RNA silencing that play
      a role in many biological processes. They are involved in the development of many
      diseases, including cancer. Extensive experimental data show that they play a
      role in the pathogenesis of cancer as well as the development of drug resistance
      during treatments. The aim of this work was to detect differentially expressed
      miRNAs in MTX-resistant cells. Thus, miRNA microarrays of sensitive and MTX
      resistant HT29 colon cancer cells were performed. The results were analyzed using
      the GeneSpring GX11.5 software. Differentially expressed miRNAs in resistant
      cells were identified and miR-224, which was one of the most differentially
      expressed miRNAs and with high raw signal values, was selected for further
      studies. The underexpression of miR-224 was also observed in CaCo-2 and K562
      cells resistant to MTX. Putative targets were predicted using TargetScan 5.1
      software and integrated with the data from expression microarrays previously
      performed. This approach allowed us to identify miR-224 targets that were
      differentially expressed more than 2-fold in resistant cells. Among them CDS2,
      DCP2, HSPC159, MYST3 and SLC4A4 were validated at the mRNA level by qRT-PCR.
      Functional assays using an anti-miR against miR-224 desensitized the cells
      towards MTX, mimicking the resistant phenotype. On the other hand, siRNA
      treatment against SLC4A4 or incubation of Poly Purine Reverse Hoogsteen (PPRH)
      hairpins against CDS2 or HSPC159 increased sensitivity to MTX. These results
      revealed a role for miR-224 and its targets in MTX resistance in HT29 colon
      cancer cells.

PMID- 21864508
TI  - H1, a derivative of Tetrandrine, exerts anti-MDR activity by initiating intrinsic
      apoptosis pathway and inhibiting the activation of Erk1/2 and Akt1/2.
AB  - Currently, multi-drug resistance (MDR) to anticancer drugs is a major obstacle to
      successful treatment of cancer. Looking for novel compounds with anti-MDR
      activity is an effectively way to overcome cancer drug resistance. Here, we found
      that H1, a novel derivate of Tetrandrine, displayed anti-MDR activity in vitro
      and in vivo. Average resistant factor of H1 is only 1.6. In KB and KBv200 cancer
      cells xenograft mice, H1 also displayed favorable anti-MDR activity. It could
      induce typical apoptosis as indicated by morphologic changes, DNA fragmentation
      in sensitive and resistant cancer cells. Further studies showed that H1 treatment
      resulted in the increase of ROS generation, elevation of the Bax/Bcl-2 ratio,
      loss of mitochondrial transmembrane potential (DeltaPsi(m)), release of
      cytochrome c and AIF from mitochondria into cytosol, and activation of caspase-9
      and caspase-3, but had no effect on activation of caspase-8 and the expression of
      Fas/FasL. On the other hand, H1 also inhibited survival pathways such as the
      activation of Erk1/2 and Akt1/2. In conclusion, H1 exerts good anti-MDR activity
      in vitro and in vivo, its mechanisms may be associated with initiating intrinsic
      apoptosis pathway and inhibiting the activation of Erk1/2 and Akt1/2. These
      findings further support the potential of H1 to be used in clinical trial of MDR
      cancer treatment.

PMID- 21864509
TI  - Functional analysis of pharmacogenetic variants of human organic cation/carnitine
      transporter 2 (hOCTN2) identified in Singaporean populations.
AB  - The human organic cation/carnitine transporter-2 (hOCTN2; SLC22A5) mediates the
      cellular influx of organic cations such as carnitine, which is essential for
      fatty acid oxidation. Primary carnitine deficiency has been associated with a
      wide range of hOCTN2 gene mutations. Six novel nonsynonymous single nucleotide
      polymorphisms in the hOCTN2 gene were identified recently in Chinese and Indian
      populations of Singapore. The present study evaluated the impact of these
      polymorphisms on hOCTN2 function and expression in HEK-293 cells. Transport
      function was markedly impaired in variants that encoded amino acid substitutions
      D122Y (<20% of wild-type control) and K302E (~45% of wild-type) in the large
      extracellular loop and large intracellular loop of hOCTN2, respectively. The
      function of the other four variants was unimpaired (E109K, V175M, K191N and
      A214V). From biotinylation and immunofluorescence experiments, the expression of
      the D122Y and K302E-hOCTN2 variants at the plasma membrane of HEK-293 cells was
      decreased relative to the wild-type hOCTN2 but total cellular expression was
      unchanged. Transporter kinetic studies indicated a decrease in the V(max) for l
      carnitine influx by K302E-hOCTN2 to 49% of wild-type control, while K(m) remained
      unchanged; kinetic evaluation of D122Y-hOCTN2 was not possible due to its low
      transport function. The K302E-hOCTN2 variant was also more susceptible than the
      wild-type transporter to inhibition by the drugs cimetidine, pyrilamine and
      verapamil. These findings indicate that impaired plasma membrane targeting of the
      D122Y and K302E-hOCTN2 variants that occur in Singaporean populations contributes
      to decreased carnitine influx.

PMID- 21864510
TI  - The tyrphostin AG1478 inhibits proliferation and induces death of liver tumor
      cells through EGF receptor-dependent and independent mechanisms.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related
      death. Different signaling pathways are de-regulated in this pathogenesis, among
      them the epidermal growth factor receptor one (EGFR/Erb1). Here we show that
      blockage of this pathway by the tyrphostin 4-(3-chloroanilino)-6,7
      dimethoxyquinazoline (AG1478) in different liver tumor cell lines promotes both
      inhibition of cell proliferation and induction of cell death, which are
      coincident with arrest in the G1 phase of the cell cycle, caspase-3 activation
      and DNA fragmentation. AG1478 up-regulates the expression of the pro-apoptotic
      member of the BCL-2 family BIM and down-regulates the expression of the anti
      apoptotic BCL-XL and MCL1. Furthermore, it also decreases the levels of the
      caspase inhibitors HIAP2 and XIAP. The treatment of HCC cells with AG1478
      enhanced the apoptosis induced by other pro-apoptotic stimuli, such as the
      physiological cytokine, TGF-beta, highly expressed in liver tumors, or the
      chemotherapeutic drug doxorubicin. The effects observed by AG1478 were broader
      than the ones seen by silencing of the EGFR with siRNA, which indicates that this
      drug might act on other targets different from the EGFR. In this same line of
      evidence, AG1478 retained some cytotoxic effects in cells where EGFR has been
      targeted knock-down with shRNA. Interestingly, AG1478 preferentially acts on
      liver tumor cells, being untransformed cells much less responsive to its
      cytotoxic effects. In conclusion, AG1478 could be a potential therapeutic drug to
      be used in HCC.

PMID- 21864511
TI  - Propiconazole increases reactive oxygen species levels in mouse hepatic cells in
      culture and in mouse liver by a cytochrome P450 enzyme mediated process.
AB  - Propiconazole induces hepatocellular carcinomas and hepatocellular adenomas in
      mice and promotes liver tumors in rats. Transcriptional, proteomic, metabolomic
      and biochemical studies of hepatic tissues from mice treated with propiconazole
      under the conditions of the chronic bioassay indicated that propiconazole induced
      oxidative stress. Here we sought to identify the source of the reactive oxygen
      species (ROS) induced by propiconazole using both AML12 immortalized mouse
      hepatocytes in culture and liver tissues from mice. We also sought to further
      characterize the nature and effects of ROS formation induced by propiconazole
      treatment in mouse liver. ROS was induced in AML12 cells by propiconazole as
      measured by fluorescence detection and its formation was ameliorated by N
      acetylcysteine. Propiconazole induced glutathione-S-transferase (GSTalpha)
      protein levels and increased the levels of thiobarbituric acid reactive
      substances (TBARS) in AML12 cells. The TBARS levels were decreased by diphenylene
      iodonium chloride (DPIC), a cytochrome P450 (CYP) reductase inhibitor revealing
      the role of CYPs in ROS generation. It has been previously reported that Cyp2b
      and Cyp3a proteins were induced in mouse liver by propiconazole and that Cyp2b
      and Cyp3a proteins undergo uncoupling of their CYP catalytic cycle releasing ROS.
      Therefore, salicylic acid hydroxylation was used as probe for ROS formation using
      microsomes from mice treated with propiconazole. These studies showed that levels
      of 2,3-dihydroxybenzoic acid (an ROS derived metabolite) were decreased by
      ketoconazole, melatonin and DPIC. In vivo, propiconazole increased hepatic
      malondialdehyde levels and GSTalpha protein levels and had no effect on hepatic
      catalase or superoxide dismutase activities. Based on these observations we
      conclude that propiconazole induces ROS in mouse liver by increasing CYP protein
      levels leading to increased ROS levels. Our data also suggest that propiconazole
      induces the hydroxyl radical as a major ROS form.

PMID- 21864513
TI  - Protective role of sinapic acid against arsenic: induced toxicity in rats.
AB  - Arsenic compounds are classified as toxicants and human carcinogens.
      Environmental exposure to arsenic imposes a big health issue worldwide. Sinapic
      acid is a phenylpropanoid compound and is found in various herbal materials and
      high-bran cereals. It has been reported that sinapic acid has antioxidant
      efficacy as metal chelators due to the orientation of functional groups. However,
      it has not yet been examined in experimental animals. In light of this fact, the
      purpose of this study was to characterize the protective role of sinapic acid
      against arsenic induced toxicity in rats. Rats were orally treated with arsenic
      alone (5mg/kg body weight (bw)/day) plus sinapic acid at different doses (10, 20
      and 40mg/kg bw/day) for 30days. Hepatotoxicity was measured by the increased
      activities of serum hepatospecific enzymes namely aspartate transaminase, alanine
      transaminase, alkaline phosphatase, gamma glutamyl transferase, lactate
      dehydrogenase and total bilirubin along with increased elevation of lipid
      peroxidative markers, thiobarbituric acid reactive substances, lipid
      hydroperoxides, protein carbonyl content and conjugated dienes. The toxic effect
      of arsenic was also indicated by significantly decreased activities of enzymatic
      antioxidants like superoxide dismutase, catalase, glutathione peroxidase,
      glutathione-S-transferase, glutathione reductase and glucose-6-phosphate
      dehydrogenase along with non-enzymatic antioxidant like reduced glutathione.
      Administration of sinapic acid exhibited significant reversal of arsenic induced
      toxicity in hepatic tissue. The effect at a dose of 40mg/kgbw/day was more
      pronounced than the other two doses (10 and 20mg/kgbw/day). All these changes
      were supported by reduction of arsenic concentration and histopathological
      observations of the liver. These results suggest that sinapic acid has a
      protective effect over arsenic induced toxicity in rat.

PMID- 21864512
TI  - Specific and prolonged proteasome inhibition dictates apoptosis induction by
      marizomib and its analogs.
AB  - Marizomib (NPI-0052) is a naturally derived irreversible proteasome inhibitor
      that potently induces apoptosis via a caspase-8 and ROS-dependent mechanism in
      leukemia cells. We aim to understand the relationship between the irreversible
      inhibition of the proteasome and induction of cell death in leukemia cells by
      using analogs of marizomib that display reversible and irreversible properties.
      We highlight the importance of sustained inhibition of at least two proteasome
      activities as being key permissive events for the induction of the apoptotic
      process in leukemia cells. These data provide the basis for the development of
      new approaches to generate more effective anti-proteasome therapies.

PMID- 21864514
TI  - d-Ribose glycates beta(2)-microglobulin to form aggregates with high cytotoxicity
      through a ROS-mediated pathway.
AB  - beta(2)-Microglobulin (beta(2)M) modified with advanced glycation end products
      (AGEs) is a major component of the amyloid deposits in hemodialysis-associated
      amyloidosis (HAA). However, the effect of glycation on the misfolding and
      aggregation of beta(2)M has not been studied so far. Here we examine the
      molecular mechanism of aggregate formation of HAA-related ribosylated beta(2)M in
      vitro. We find that the glycating agent d-ribose interacts with human beta(2)M to
      generate AGEs that form aggregates in a time-dependent manner. Ribosylated
      beta(2)M molecules are highly oligomerized compared with unglycated beta(2)M, and
      have granular morphology. Furthermore, such ribosylated beta(2)M aggregates show
      significant cytotoxicity to both human SH-SY5Y neuroblastoma and human foreskin
      fibroblast FS2 cells and induce intracellular reactive oxygen species (ROS).
      Presence of the antioxidant N-acetylcysteine (1.0mM) attenuated intracellular ROS
      and prevented cell death induction in both SH-SY5Y and FS2 cells, indicating that
      the cytotoxicity of ribosylated beta(2)M aggregates depends on a ROS-mediated
      pathway in both cell lines. In other words, d-ribose reacts with beta(2)M and
      induces the ribosylated protein to form granular aggregates with high
      cytotoxicity through a ROS-mediated pathway. These findings suggest that
      ribosylated beta(2)M aggregates could contribute to the dysfunction and death of
      cells and could play an important role in the pathogenesis of beta(2)M-associated
      diseases such as HAA.

PMID- 21864515
TI  - Brominated aliphatic hydrocarbons and sterols from the sponge Xestospongia
      testudinaria with their bioactivities.
AB  - Four brominated aliphatic hydrocarbons (1-4), including a novel brominated ene
      tetrahydrofuran named as mutafuran H (1), and five sterols (5-9) were isolated
      from the South China Sea sponge Xestospongia testudinaria. The structure of 1 was
      determined on the basis of NMR ((1)H, (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, and
      NOESY), MS, and optical rotation analysis. Known compounds were identified by
      comparison of their NMR data with those reported in the literature. Compounds 1
      4, and 6-9 were evaluated for their toxicity against Artemia salina larvae, and
      anti-acetylcholinesterase activity.

PMID- 21864516
TI  - Epoxy ceriporic acid produced by selective lignin-degrading fungus Ceriporiopsis
      subvermispora.
AB  - Ceriporiopsis subvermispora is a selective white rot basidiomycete which degrades
      lignin in wood at a distance far from enzymes. Low molecular mass metabolites
      play a central role in the oxidative degradation of lignin. To understand the
      unique wood-decaying mechanism, we surveyed the oxidized derivatives of ceriporic
      acids (alk(en)ylitaconic acids) produced by C. subvermispora using high
      resolution liquid chromatography multiple-stage mass spectrometry (HR-LC/MS(n)).
      The analysis of the precursor and product ions from the extract suggested that an
      epoxidized derivative of ceriporic acid is produced by the fungus. To identify
      the new metabolite, an authentic compound of ceriporic acid epoxide was
      synthesized in vitro by reacting (R)-3-[(Z)-hexadec-7-enyl]-itaconic acid
      (ceriporic acid C) with m-chloroperbenzoic acid. The precursor and product ions
      from the natural metabolite and authentic epoxide were identical and
      distinguishable from those of hydroxy and hydroperoxy derivatives after reduction
      with NaBD(4). Feeding experiments with [U-(13)C]-glucose, 99% and the subsequent
      analyses of the first and second generation product ions demonstrated that the
      oxidized ceriporic acid was (R)-3-(7,8-epoxy-hexadecyl)-itaconic acid. To our
      knowledge, this study is the first to report that natural alkylitaconic acid
      bears an epoxy group on its side chain.

PMID- 21864517
TI  - Total hCG tests.
AB  - INTRODUCTION: There are 12 types of automated total hCG tests sold today, the
      Abbott Architect, Abbott AxSym, the Beckman Access 2. Beckman DxI 800, the Ortho
      Vitros EciQ, Roche Elecsys hCG+beta, Siemens ACS180, Siemens Centaur, Siemens
      Dimension, Siemens Immulite and Siemens Stratus, and the Tosoh A1A. All tests
      claim to be total hCG tests but do not define what total means. Total hCG test
      needs to detect all hCG variants in order to be used for all hCG test clinical
      applications. Here we assess this ability. METHODS: Coded samples of pure hCG,
      nicked hCG, hyperglycosylated hCG, nicked hCG missing C-terminal peptide, nicked
      hyperglycosylated hCG, asialo hCG, hCGbeta, nicked hCGbeta and beta-core fragment
      were tested blindly in serum and urine at 10 independent laboratories. RESULTS:
      While the Siemens Immulite total hCG test detected 8 of 9 hCG variant standards,
      other assays poorly detected important determinants such as nicked hCG missing
      the C-terminal peptide, beta-core fragment, hyperglycosylated hCG, nicked hCG,
      asialo hCG, and hCGbeta. Four assay appropriately detected 4 of 9 variants, 2
      assays detected 3 of 9, 4 assays detected 2 of 9 and 1 assay only appropriately
      detected 1 of 7 hCG variants. DISCUSSION: Care is needed in selecting a total hCG
      test. The Siemens Immulite tests performed best at detecting all the hCG variants
      making it appropriate for all applications. Nine assays had limited applications,
      3 of the assays were appropriate for advanced pregnancy testing only.

PMID- 21864518
TI  - Complementarily of urine analysis and serum free light chain assay for assessing
      response treatment response: illustrated by three case examples.
AB  - BACKGROUND: With the introduction of a new sensitive serum assay for monoclonal
      free light chains (FLC), there is a question as to whether or not traditional
      urine immunofixation electrophoresis (IFE) is still necessary. Therapy for B-cell
      disease has greatly improved in recent time so that noninvasive biomarkers that
      suggest complete remissions have become increasingly important. A Consensus
      Opinion stated that because of methodological imperfections, at concentrations of
      FLC <100 mg/l, urine IFE should supplement serum FLC ratio. METHODS: Examples are
      presented from a review of laboratory results and medical records from 3 patients
      on treatment after diagnosis of amyloidosis AL and multiple myeloma. RESULTS:
      Monoclonal FLC was identified in urine by IFE while the kappa/lambda ratio from
      the serum FLC assay was within the reference range. CONCLUSION: The results from
      these 3 cases suggest that as the FLC concentration drops, the serum FLC results
      may become more ambiguous. These results are consistent with guidelines
      cautioning about conclusions drawn from the serum FLC assay alone. Although more
      study is needed, the examples presented here illustrate that traditional urine
      IFE appear to adds important information regarding potential complete remissions
      and remains an important complementary assay to the serum FLC assay.

PMID- 21864519
TI  - Apolipoprotein E polymorphisms and sleep quality in obstructive sleep apnea
      syndrome.
AB  - BACKGROUND: The purpose of this study was to evaluate the influence of
      polymorphism on sleep parameters of Obstructive Sleep Apnea Syndrome (OSAS)
      patients. METHODS: Patients were genotyped after a full-night polysomnography
      using the large Epidemiologic Sleep Study of Sao Paulo population-based sample.
      RESULTS: Individuals who carry the APOE epsilon2 allele showed longer sleep
      latency, lower sleep efficiency and higher numbers of arousals/hour, when
      compared to epsilon3 allele homozygous and carriers of epsilon4 allele (p<0.05).
      These findings remained significant even after correction for potential
      confounders, such as sex, age and African genetic ancestry. CONCLUSION: The APOE
      polymorphisms may modulate the effects of intermittent hypoxia and sleep
      fragmentation in the sleep architecture of OSAS patients, and that the presence
      of the epsilon2 allele may serve as a biological marker for the identification of
      a subgroup of patients who are more likely to suffer with OSAS detrimental
      effects on sleep, impacting not only the daily functioning, but also their
      quality of life.

PMID- 21864520
TI  - Budget impact of using midnight salivary cortisol in the diagnosis of
      hypercortisolism.
AB  - BACKGROUND: A single midnight serum cortisol (MSC) test has been reported to
      possess the best sensitivity and specificity for diagnosing Cushing's syndrome
      (CS). However, this test requires patient hospitalization, making it costly. This
      paper aims to compare the hospital budget impact and accuracy of using midnight
      salivary cortisol (MSVC), as opposed to MSC, in the diagnosis of
      hypercortisolism. METHODS: 77 patients with at least two high urinary free
      cortisol (UFC) values (>360 nmol/24 h) were selected from 611 patients with
      clinical symptoms of CS. The costs of the method to confirm the diagnosis of
      hypercortisolism was calculated comparing Option A using MSC (UFCx2, low-dose
      dexamethasone suppression test [LDDST]) that requires patient hospitalization
      versus Option B using MSVC (UFCx2, LDDST) in which the evaluation is done outside
      the Hospital. A budget impact analysis for one year was developed, and a
      sensitivity analysis in different scenarios was performed. Reproducibility and
      diagnostic performance of MSVC and MSC were also measured. RESULTS: Salivary
      cortisol is a sound analytical method for evaluating free serum cortisol due to
      its classification accuracy, good imprecision, linearity, and stability. AUC(ROC)
      comparison between MSVC and MSC shows no significant differences. The
      substitution of the MSC for MSVC in our hospital could save between ?16,762 and
      ?132,804 in one year. CONCLUSIONS: The use of MSVC in the diagnosis of
      hypercortisolism can result in a substantial decrease in the budget impact,
      without losing diagnosis accuracy and reliability, a significant advantage
      considering the current emphasis on reducing the financial burden of health care.

PMID- 21864521
TI  - Plasma CCN2 (connective tissue growth factor; CTGF) is a potential biomarker in
      idiopathic pulmonary fibrosis (IPF).
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and
      fatal pulmonary fibrotic disease and useful biomarkers are required to diagnose
      and predict disease activity. CCN2 (connective tissue growth factor; CTGF) has
      been reported as one of the key profibrotic factors associated with transforming
      growth factor-beta (TGF-beta), and its assay has potential as a non-invasive
      measure in various fibrotic diseases. Recently, we developed a new subtraction
      method for determination of plasma CCN2 levels. We examined the utility of plasma
      CCN2 levels as a surrogate marker in IPF. METHODS: Plasma CCN2 levels were
      calculated in 33 patients with IPF, 14 patients with non-IPF idiopathic
      interstitial pneumonias (IIPs) and 101 healthy volunteers by sandwich enzyme
      linked immunosorbent assay (ELISA) using specific monoclonal antibodies for two
      distinct epitopes of human CCN2. We evaluated the utility of plasma CCN2 levels
      by comparison with clinical parameters. RESULTS: Plasma CCN2 levels were
      significantly higher in patients with IPF than in those with non-IPF IIPs and
      healthy volunteers. Importantly, plasma CCN2 levels showed significantly negative
      correlation with 6-month change of forced vital capacity (FVC) in patients with
      IPF. CONCLUSIONS: Plasma CCN2 is a potential biomarker for IPF.

PMID- 21864522
TI  - Daytime triglyceride variability in men and women with different levels of
      triglyceridemia.
AB  - BACKGROUND: Triglyceride (TG) levels measured in either the fasting or non
      fasting state predict the risk of cardiovascular disease (CVD). Since CVD risk
      assessment is affected by variability in TG, the aim of the study was to
      investigate intra-individual variability of non-fasting TG. METHODS: Capillary
      triglyceride (cTG) levels were measured in 246 free-living individuals at six
      time-points during the day on three separate occasions. Intra-individual
      variability in cTG was assessed by calculating the standard deviation of three
      measures at each time-point. Subjects were analyzed by gender and by fasting TG
      level. RESULTS: In the fasting state, intra-individual variability was similar in
      males and females (0.28 and 0.35 mmol/l, respectively), but increased
      significantly in male but not in female subjects during the day, i.e., 0.28 to
      0.69, and 0.35 to 0.36 mmol/l, resp. Subjects with higher fasting TG levels had
      greater absolute variability in both fasting and non-fasting TG. CONCLUSIONS: The
      variability in non-fasting TG is greater in males and in individuals with higher
      levels of TG. Since greatest variability in non-fasting TG occurs very late in
      the day, it is unlikely to affect the assessment of CVD risk, which is based on a
      blood sample taken during daylight hours.

PMID- 21864523
TI  - Reference values for venous and capillary S100B in children.
AB  - BACKGROUND: The current management guidelines for pediatric mild head injury
      (MHI) liberally recommend computed tomography (CT) and frequent admission. Serum
      protein S100B, currently used in management of adult head injury, has recently
      shown potential for reducing unnecessary CT scans after pediatric mild head
      injury. Capillary sampling in children is commonly used when venous sampling
      fails or is inappropriate. We present reference values for both venous and
      capillary samples of protein S100B in children. METHODS: Neurologically healthy
      children aged 1-16, scheduled for minor surgery requiring general anesthesia,
      were prospectively included. Samples for S100B were drawn before (venous) and
      after (venous and capillary) sedation. RESULTS: Serum values of 455 children (255
      boys, 200 girls) aged 1-14 were computed. S100B was higher in younger children
      for both venous (r=-0.32) and capillary samples (r=-0.28). Reference levels for
      children aged 1 and 2 were significantly higher than for children aged 3-14 years
      (venous 0.15 MUg/L, capillary 0.37 MUg/L). For capillary blood, a gender
      difference was found in the youngest age groups. CONCLUSIONS: We present
      reference values for venous and capillary S100B in healthy children. These
      results can be utilized when considering future studies on pediatric head injury
      and S100B levels.

PMID- 21864524
TI  - Development and evolution of the lateral plate mesoderm: comparative analysis of
      amphioxus and lamprey with implications for the acquisition of paired fins.
AB  - Possession of paired appendages is regarded as a novelty that defines crown
      gnathostomes and allows sophisticated behavioral and locomotive patterns. During
      embryonic development, initiation of limb buds in the lateral plate mesoderm
      involves several steps. First, the lateral plate mesoderm is regionalized into
      the cardiac mesoderm (CM) and the posterior lateral plate mesoderm (PLPM).
      Second, in the PLPM, Hox genes are expressed in a collinear manner to establish
      positional values along the anterior-posterior axis. The developing PLPM splits
      into somatic and splanchnic layers. In the presumptive limb field of the somatic
      layer, expression of limb initiation genes appears. To gain insight into the
      evolutionary sequence leading to the emergence of paired appendages in ancestral
      vertebrates, we examined the embryonic development of the ventral mesoderm in the
      cephalochordate amphioxus Branchiostoma floridae and of the lateral plate
      mesoderm in the agnathan lamprey Lethenteron japonicum, and studied the
      expression patterns of cognates of genes known to be expressed in these
      mesodermal layers during amniote development. We observed that, although the
      amphioxus ventral mesoderm posterior to the pharynx was not regionalized into CM
      and posterior ventral mesoderm, the lateral plate mesoderm of lampreys was
      regionalized into CM and PLPM, as in gnathostomes. We also found nested
      expression of two Hox genes (LjHox5i and LjHox6w) in the PLPM of lamprey embryos.
      However, histological examination showed that the PLPM of lampreys was not
      separated into somatic and splanchnic layers. These findings provide insight into
      the sequential evolutionary changes that occurred in the ancestral lateral plate
      mesoderm leading to the emergence of paired appendages.

PMID- 21864525
TI  - In vivo calcium dynamics during neural crest cell migration and patterning using
      GCaMP3.
AB  - Examining calcium dynamics within the neural crest (NC) has the potential to shed
      light on mechanisms that regulate complex cell migration and patterning events
      during embryogenesis. Unfortunately, typical calcium indicators are added to
      culture media or have low signal to noise after microinjection into tissue that
      severely limit analyses to cultured cells or superficial events. Here, we studied
      in vivo calcium dynamics during NC cell migration and patterning, using a
      genetically encoded calcium sensor, GCaMP3. We discovered that trunk NC cells
      displayed significantly more spontaneous calcium transients than cranial NC
      cells, and during cell aggregation versus cell migration events. Spontaneous
      calcium transients were more prevalent during NC cell aggregation into discrete
      sympathetic ganglia (SG). Blocking of N-cadherin activity in trunk NC cells near
      the presumptive SG led to a dramatic decrease in the frequency of spontaneous
      calcium transients. Detailed analysis and mathematical modeling of cell behaviors
      during SG formation showed NC cells aggregated into clusters after displaying a
      spontaneous calcium transient. This approach highlights the novel application of
      a genetically encoded calcium indicator to study subsets of cells during ventral
      events in embryogenesis.

PMID- 21864526
TI  - Inhibition of advanced glycation end products by aminoguanidine restores mast
      cell numbers and reactivity in alloxan-diabetic rats.
AB  - Mast cell number and reactivity have been shown to be down-regulated under
      diabetic conditions. This study was undertaken in order to investigate the role
      of the advanced glycation end products in the reduction of mast cell number and
      reactivity in diabetic rats. The effect of aminoguanidine on mast cell apoptosis
      was also evaluated. Diabetes was induced by intravenous injection of alloxan into
      fasted rats and aminoguanidine was administered after 3 days of diabetes
      induction, once daily for 18 consecutive days. Mast cell apoptosis and levels of
      Bax, a pro-apoptotic member of Bcl-2 family, were evaluated by TUNEL and western
      blot, respectively. Diabetes led to increased levels of fructosamine and AGEs in
      the plasma, an effect prevented by aminoguanidine. Treatment with aminoguanidine
      restored mast cell numbers in the pleural cavity and in mesenteric tissue of
      diabetic rats. Aminoguanidine also significantly reversed the diabetes-induced
      reduction in histamine release, as measured by fluorescence, following activation
      with substance P or antigen in vitro. Increased apoptosis and levels of Bax in
      mast cells from diabetic rats were inhibited by aminoguanidine. In conclusion,
      our findings showed that aminoguanidine restored the number and reactivity of
      mast cells in diabetic rats, accompanied by suppression of apoptosis, evidencing
      that advanced glycation end product formation has a critical role in mast cell
      behavior of diabetic rats.

PMID- 21864527
TI  - Circadian dysfunction in a mouse model of Parkinson's disease.
AB  - Many Parkinson's disease (PD) patients exhibit sleep disorders as part of their
      symptoms with evidence suggesting that REM sleep disorders may be intimately
      associated with this disease. Possible dysfunction in the circadian system in PD
      has received less attention, yet problems in circadian timing are common in
      neurodegenerative diseases. In the present study, we examined the expression of
      daily and circadian rhythms in the alpha-synuclein overexpressing (ASO)
      transgenic line. We found selective deficits in the expression of circadian
      rhythms of locomotor activity, including lower night-time activity and greater
      fragmentation in the wheel-running activity in this PD model. These alterations
      were prominent in young adult (3-4 mo) ASO mice and worsened progressively with
      age, consistent with prior reports of age-related loss of motor skills. The
      temporal distribution of sleep was also altered in the ASO mice compared to
      littermate controls. In the ASO mice, the peak/trough expression of the clock
      gene PERIOD2 was normal in the master pacemaker of the circadian system: the
      suprachiasmatic nucleus (SCN); however, the daytime firing rate of SCN neurons
      was reduced in the mutant mice. Together, this data raises the possibility that a
      weakening of circadian output is a core feature of PD. The reduction in magnitude
      of circadian output would be expected to have functional consequences throughout
      the body.

PMID- 21864528
TI  - Reduced striatal acetylcholine efflux in the R6/2 mouse model of Huntington's
      disease: an examination of the role of altered inhibitory and excitatory
      mechanisms.
AB  - Huntington's disease (HD) is a genetic neurodegenerative disorder that is
      characterized by the progressive onset of cognitive, psychiatric, and motor
      symptoms. In parallel, the neuropathology of HD is characterized by progressive
      loss of projection neurons in cortex and striatum; striatal cholinergic
      interneurons are relatively spared. Nonetheless, there is evidence that striatal
      acetylcholine (ACh) function is altered in HD. The present study is the first to
      examine striatal ACh function in awake, behaving animals, using the R6/2 mouse
      model of HD, which is transgenic for exon 1 of the mutant huntingtin gene.
      Physiological levels of extracellular striatal ACh were monitored in R6/2 mice
      and wild type controls using in vivo microdialysis. Results indicate that
      spontaneous ACh release is reduced in R6/2 mice relative to controls.
      Intrastriatal application of the GABA(A) antagonist bicuculline methiodide (10.0
      MUM) significantly elevated ACh levels in both R6/2 mice and wild type controls,
      while overall ACh levels were reduced in the R6/2 mice compared to the wild type
      group. In contrast, systemic administration of the D(1) dopamine receptor partial
      agonist, SKF-38393 (10.0mg/kg, IP), elevated ACh levels in control animals, but
      not R6/2 mice. Taken together, the present results suggest that GABA-mediated
      inhibition of striatal ACh release is intact in R6/2 mice, further demonstrating
      that cholinergic interneurons are capable of increased ACh release, whereas D(1)
      receptor-dependent activation of excitatory inputs to striatal cholinergic
      interneurons is dysfunctional in R6/2 mice. Reduced levels of extracellular
      striatal ACh in HD may reflect abnormalities in the excitatory innervation of
      cholinergic interneurons, which may have implications ACh-dependent processes
      that are altered in HD, including corticostriatal plasticity.

PMID- 21864530
TI  - Real-time PCR to assess the Leishmania load in Lutzomyia longipalpis sand flies:
      screening of target genes and assessment of quantitative methods.
AB  - Visceral Leishmaniasis is an endemic disease in Brazil caused by Leishmania
      infantum chagasi and its main vector species is the sand fly Lutzomyia
      longipalpis. Epidemiological studies have used conventional PCR techniques to
      measure the rate of infection of sand flies collected in the field. However, real
      time PCR can detect lower parasite burdens, reducing the number of false
      negatives and improving the quantification of Leishmania parasites in the sand
      fly. This study compared genes with various copy numbers to detect and quantify
      L. infantum chagasi in L. longipalpis specimens by real-time PCR. We mixed pools
      of 1, 10 and 30 male sand flies with various amounts of L. infantum chagasi,
      forming groups with 50, 500, 5000 and 50,000 Leishmania parasites. For the
      amplification of L. infantum chagasi DNA, primers targeting kDNA, polymerase
      alpha and the 18S ribosome subunit were employed. Parasites were measured by
      absolute and relative quantification. PCR detection using the amplification of
      kDNA exhibited the greatest sensitivity among the genes tested, showing the
      capacity to detect the DNA equivalent of 0.004 parasites. Additionally, the
      relative quantification using these primers was more accurate and precise. In
      general, the number of sand flies used for DNA extraction did not influence
      Leishmania quantification. However, for low-copy targets, such as the polymerase
      alpha gene, lower parasite numbers in the sample produced inaccurate
      quantifications. Thus, qPCR measurement of L. infantum chagasi in L. longipalpis
      was improved by targeting high copy-number genes; amplification of high copy
      number targets increased the sensitivity, accuracy and precision of DNA-based
      parasite enumeration.

PMID- 21864529
TI  - Molecular and biochemical characterisation of a Teladorsagia circumcincta
      glutamate dehydrogenase.
AB  - A full length cDNA encoding glutamate dehydrogenase was cloned from Teladorsagia
      circumcincta (TcGDH). The TcGDH cDNA (1614 bp) encoded a 538 amino acid protein.
      The predicted amino acid sequence showed 96% and 93% similarity with Haemonchus
      contortus and Caenorhabditis elegans GDH, respectively. A soluble N-terminal
      6xHis-tagged GDH protein was expressed in the recombinant Escherichia coli strain
      BL21 (DE3) pGroESL, purified and characterised. The recombinant TcGDH had similar
      kinetic properties to those of the enzyme in homogenates of T. circumcincta,
      including greater activity in the aminating than deaminating reaction. Addition
      of 1mM ADP and ATP increased activity about 3-fold in the deaminating reaction,
      but had no effect in the reverse direction. TcGDH was a dual co-factor enzyme
      that operated both with NAD(+) and NADP(+), GDH activity was greater in the
      deaminating reaction with NADP(+) as co-factor and more with NADH in the
      aminating reaction.

PMID- 21864531
TI  - The adjuvant-free immunoprotection of recombinant filarial protein Abundant
      Larval Transcript-2 (ALT-2) in Mastomys coucha and the immunoprophylactic
      importance of its putative signal sequence.
AB  - The filarial protein Abundant Larval Transcript-2 (ALT-2) of the filarial
      parasite Brugia malayi has been shown to produce 74% worm clearance when
      administered with an adjuvant. In the present study, we show that it not only
      induces humoral and cell-mediated immunity, but also protection up to 71% in
      Mastomys coucha, a permissive animal model for filariasis, even without adjuvant.
      This unique feature of ALT-2 protein is highly restricted to its 21 amino acid N
      terminal signal sequence, the absence of which resulted in poor immune response
      as well as immunoprotection (49%). Moreover, ALT-2 is likely to exert
      immunoprotection effects in B. malayi infection by maintaining a Th1-Th2 balance,
      evident from higher levels of IgG1 and IgG2a as well as IL-4 and IFN-gamma. An
      improved understanding about the role of this filarial protein in host immunity,
      host-parasite interaction and worm clearance will aid in the development of good
      immunoprophylaxis for the disease.

PMID- 21864532
TI  - Enlightening the molecular basis of trypanothione specificity in trypanosomatids:
      mutagenesis of Leishmania infantum glyoxalase II.
AB  - Leishmania infantum glyoxalase II shows absolute specificity towards its
      trypanothione thioester substrate. In the previous work, we performed a
      comparative analysis of glyoxalase II structures determined by X-ray
      crystallography which revealed that Tyr291 and Cys294, absent in the human
      homologue, are essential for substrate binding. To validate this trypanothione
      specificity hypothesis we produced a mutant L. infantum GLO2 enzyme by replacing
      Tyr291 and Cys294 by arginine and lysine, respectively. This new enzyme is
      capable to use the glutathione thioester substrate, with kinetic parameters
      similar to the ones from the human enzyme. Substrate specificity is likely to be
      mediated by spermidine moiety binding, providing a primer for understanding the
      molecular basis of trypanothione specificity.

PMID- 21864533
TI  - Molecular identification of three Trichinella isolates from Heilongjiang
      Province, People's Republic of China.
AB  - DNAs of Trichinella dog isolate (HC), Trichinella swine isolate (HH) and
      Trichinella cat isolate (SW), obtained from Heilongjiang Province, were amplified
      by the fragments of 18S rDNA and ITS2. Two reference strains, Trichinella
      spiralis (ISS3) and Trichinella nativa (ISS10) were used for sequence comparison.
      Sequence and dendrogram analysis indicated that HC belonged to T. nativa and HH
      together with SW belonged to T. spiralis. This method permits rapid species
      identification of Trichinella isolates, although further evaluation is required
      before precisely identification.

PMID- 21864534
TI  - Brucella adaptation and survival at the crossroad of metabolism and virulence.
AB  - "In vivo" bacterial nutrition, i.e. the nature of the metabolic network and
      substrate(s) used by bacteria within their host, is a fundamental aspect of
      pathogenic or symbiotic lifestyles. A typical example are the Brucella spp.,
      facultative intracellular pathogens responsible for chronic infections of animals
      and humans. Their virulence relies on their ability to modulate immune response
      and the physiology of host cells, but the fine-tuning of their metabolism in the
      host during infection appears increasingly crucial. Here we review new insights
      on the links between Brucella virulence and metabolism, pointing out the need to
      investigate both aspects to decipher Brucella infectious strategies.

PMID- 21864536
TI  - Effects of male nutrition on sperm storage and remating behavior in wild and
      laboratory Anastrepha fraterculus (Diptera: Tephritidae) females.
AB  - Male physiological condition can affect his ability to modulate female sexual
      receptivity. Thus, studying this aspect can have biological and practical
      implications. Here, we examine how male nutritional status affected the amount of
      sperm stored, remating rate and refractory period of the tephritid fruit fly
      Anastrepha fraterculus (Wiedemann) females. Both wild and laboratory flies were
      evaluated. We also examine female sperm storage patterns. Experiments were
      carried out by manipulating male adult diet and exposing these males to virgin
      females. Females mated with differently treated males were either dissected to
      count the amount of sperm stored or exposed to virgin males to determine remating
      rate and the length of the refractory period. We found that male nutritional
      status affected the amount of the sperm stored and the renewal of sexual
      receptivity in wild flies. For laboratory flies, male nutritional status affected
      the length of the refractory period but not the amount of sperm stored by
      females. In addition, we report that the ventral receptacle is not an important
      organ of sperm storage in this species. We conclude that male nutritional
      condition influences the ability to modulate female sexual receptivity, possibly
      through a combination of the quantity and quality of the ejaculate. From an
      applied perspective, providing males with an enriched diet will likely result in
      increased efficacy of the sterile insect technique.

PMID- 21864535
TI  - Promoting myelin repair and return of function in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS.
      Conduction block in demyelinated axons underlies early neurological symptoms, but
      axonal transection and neuronal loss are believed to be responsible for more
      permanent chronic deficits. Several therapies are approved for treatment of
      relapsing-remitting MS, all of which are immunoregulatory and clinically proven
      to reduce the rate of lesion formation and exacerbation. However, existing
      approaches are only partially effective in preventing the onset of disability in
      MS patients, and novel treatments to protect myelin-producing oligodendrocytes
      and enhance myelin repair may improve long-term outcomes. Studies in vivo in
      genetically modified mice have assisted in the characterization of mechanisms
      underlying the generation of neuropathology in MS patients, and have identified
      potential avenues for oligodendrocyte protection and myelin repair. However, no
      treatments are yet approved that target these areas directly, and in addition,
      the relationship between demyelination and axonal transection in the lesions of
      the disease remains unclear. Here, we review translational research targeting
      oligodendrocyte protection and myelin repair in models of autoimmune
      demyelination, and their potential relevance as therapies in MS.

PMID- 21864538
TI  - Structural organisation of the rotavirus nonstructural protein NSP5.
AB  - Rotavirus is one of the leading agents of gastroenteritis worldwide. During
      infection, viral factories (viroplasms) are formed. The rotavirus nonstructural
      proteins NSP5 and NSP2 are the major building blocks of viroplasms; however, NSP5
      function and organisation remain elusive. In this report, we present a structural
      characterisation of NSP5. Multi-angle laser light scattering, sedimentation
      velocity and equilibrium sedimentation experiments demonstrate that recombinant
      full-length NSP5 forms a decamer in solution. Far-Western, pull-down and multi
      angle laser light scattering experiments show that NSP5 has two oligomerisation
      regions. The first region, residues 103-146, is involved in NSP5 dimerisation,
      whereas the second region, residues 189-198, is responsible for NSP5
      decamerisation. Circular dichroism analyses of full-length and truncated forms of
      NSP5 reveal that the decamerisation region is helical, whereas the dimerisation
      region involves beta-sheets. From these circular dichroism experiments, we also
      show that the NSP5 protomers contain two alpha-helices, a disordered N-terminal
      half and a C-terminal half that is primarily composed of beta-sheet folds. This
      extensive structural characterisation of NSP5 led us to propose a model for its
      quaternary organisation. Finally, co-expression of NSP5 fragments and NSP2 in
      uninfected cells shows that the NSP5 decamerisation region is required for
      viroplasm-like structure formation. However, in vitro, the NSP5 decamerisation
      region partially inhibits the NSP2-NSP5 interaction. Our NSP5 model suggests that
      steric hindrance prevents NSP2 from binding to all NSP5 protomers. Some protomers
      may thus be free to interact with other NSP5 binding partners, such as viral RNAs
      and the viral polymerase VP1, to perform functions other than viroplasm
      organisation.

PMID- 21864537
TI  - Ca2+ dynamics in the mitochondria - state of the art.

PMID- 21864539
TI  - Peptidoglycan remodeling in Mycobacterium tuberculosis: comparison of structures
      and catalytic activities of RipA and RipB.
AB  - The success of Mycobacterium tuberculosis in sustaining long-term survival within
      the host macrophages partly relies on its unique cell envelop that also confers
      low susceptibility to several antibiotics. Remodeling of the septal peptidoglycan
      (PG) has been linked to the putative PG hydrolases RipA and RipB. The crystal
      structures of RipB (Rv1478) and the homologous module of RipA (Rv1477) were
      determined to 1.60 A and 1.38 A resolution, respectively. Both proteins contain a
      C-terminal core domain resembling the NlpC-type PG hydrolases. However, the
      structure of RipB exhibits striking differences to the structures of this domain
      in RipA reported here and previously by others. Major structural differences were
      found in the N-terminal segments of 70 amino acids and in an adjacent loop, which
      form part of the substrate binding groove. Both RipA and RipB are able to bind
      PG. RipA, its C-terminal module and RipB cleave defined PG fragments between d
      glutamate and meso-diaminopimelate with pH optima of 5 and 6, respectively. The
      peptidase module of RipA is also able to degrade Bacillus subtilis PG, which
      displays peptide stems and cross-links identical with those found in
      mycobacterial murein. RipB did not show comparable hydrolase activity with this
      substrate. Removal of the N-terminal segments previously suggested to have a role
      in auto-inhibition did not change the activity of either RipA or RipB. A
      comparison of the putative active-site clefts in the two enzymes provides
      structural insights into the basis of the differences in their substrate
      specificity.

PMID- 21864540
TI  - Dependence of morphometric allometries on the growth kinetics of body parts.
AB  - As overall size varies, the sizes of body parts of many animals often appear to
      be related to each other by a power law, commonly called the allometric equation.
      Orderly scaling relationships among body parts are widespread in the animal
      world, but there is no general agreement about how these relationships come
      about. Presumably they depend on the patterns of growth of body parts, and simple
      analyses have shown that exponential growth can lead to size relationships that
      are well-described by the allometric equation. Exponential growth kinetics also
      allow for a simple biological interpretation of the coefficients of the power
      relationship. Nevertheless, many tissues do not grow with exponential kinetics,
      nor do they grow for the same period of time, and the consequences of more
      realistic growth patterns on the resulting allometric relationships of body parts
      are not well understood. In this paper I derive a set of allometric equations
      that assume different kinetics of growth: linear, exponential and sigmoidal. In
      these derivations I also include differences in development times as a variable,
      in addition to differences in the growth rates and initial sizes of the two
      structures whose allometric relationship is compared. I show how these equations
      can be used to deduce the effect of different causes of variation in absolute
      size on the resulting allometry. Variation in size can be due to variation in the
      duration of development, variation in growth rate or variation in initial size. I
      show that the meaning of the coefficients of the allometric equation depends on
      exactly how size variation comes about. I show that if two structures are assumed
      to grow with sigmoidal kinetics (logistic and Gompertz) the resulting allometric
      equations do not have a simple and intuitive structure and produce graphs that,
      over a sufficiently large range of sizes, can vary from linear, to sigmoidal to
      hump-shaped. Over a smaller range of absolute sizes, these sigmoid growth
      kinetics can produce nearly linear allometries in both the arithmetic and
      logarithmic domains. I will argue that although growth kinetics are likely to be
      sigmoidal in most cases, natural selection will restrict variation in absolute
      size and the parameters of growth kinetics to regions where the allometric
      relations are linear, or nearly so.

PMID- 21864541
TI  - Mathematical model for the homeostasis of alpha-macroglobulins in the rat.
AB  - Alpha-macroglobulins (AM) are proteins that inactivate proteinases. Sodium
      monofluorophosphate (MFP) binds to AM and transiently changes AM plasma levels.
      As a consequence MFP is useful to modify AM homeostasis. A mathematical model to
      study the homeostasis of AM is proposed in this paper. The model describes
      changes in plasma concentration of AM, MFP concentration in the gastrointestinal
      tract, MFP plasma concentration, plasma concentration of AMMFP and includes rate
      constants of the processes involved in AM homeostasis. Estimation of the rate
      constants values was achieved using experimental and mathematical resources. The
      homeostasis of AM after an oral dose of 80 MUmol of MFP was analyzed with a
      simulation tool. Experimental conditions that modify the homeostasis of AM had
      been simulated and validated using specific drugs that change some parameter of
      the system. The mathematical model describes accurately the behavior of the
      biological model. The results allow concluding that the simplifications made did
      not underestimate the main processes involved in the homeostasis and, also that
      the assumptions made were correct.

PMID- 21864542
TI  - Exploitation of a single species by a threshold management policy.
AB  - Continuous time models of single exploited populations usually generate outcomes
      expressing a dependence of yield and economic items on harvest intensity. In this
      work it is shown that a known threshold policy is able to generate yield and
      related economic items that do not depend on harvest intensity, but rather on the
      values of the population threshold itself and the species intrinsic parameters.
      It is argued that since this result can be carried over to other models of single
      species dynamics, it may have significant implications in the management and
      conservation of exploited populations.

PMID- 21864543
TI  - Neutrophil transmigration, focal adhesion kinase and endothelial barrier
      function.
AB  - Neutrophil activation is an essential component of innate immune defense against
      infection and injury. In response to inflammatory stimulation, circulating
      neutrophils undergo a series of dynamic and metabolic changes characterized by
      beta2-intergrin mediated adhesion to microvascular endothelium and subsequent
      transendothelial migration. During this process, neutrophils release granular
      contents containing digestive enzymes and produce cytotoxic agents such as
      reactive oxygen species and cytokines. These products target endothelial barriers
      inducing phosphorylation-triggered junction dissociation, actin stress fiber
      formation, and actomyosin contraction, manifest as paracellular
      hyperpermeability. Endothelial cell-matrix focal adhesions play an integral role
      in this process by providing structural support for endothelial conformational
      changes that facilitate neutrophil transmigration, as well as by recruiting
      intracellular molecules that constitute the hyperpermeability signaling cascades.
      As a central connector of the complex signaling network, focal adhesion kinase
      (FAK) is activated following neutrophil adhesion, and further mediates the
      reorganization of endothelial integrin-matrix attachments in a pattern
      coordinating with cytoskeleton contraction and junction opening. In this review,
      we present recent experimental evidence supporting the importance of FAK in
      neutrophil-dependent regulation of endothelial permeability. The discussion
      focuses on the mechanisms by which neutrophils activate FAK and its downstream
      effects on endothelial barriers.

PMID- 21864545
TI  - Boswellic acid inhibits inflammatory angiogenesis in a murine sponge model.
AB  - The aim of the present study was to investigate the effects of boswellic acid
      (BA) on key components of inflammatory angiogenesis in the murine cannulated
      sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a
      framework for fibrovascular tissue growth, were implanted in Swiss albino mice
      and BA (12.5 or 25mg/kg/day) was given through installed cannulas for nine days.
      The implants collected at day 9 post-implantation were processed for the
      assessment of hemoglobin (Hb). Relevant levels of inflammatory, angiogenic and
      fibrogenic cytokines were also determined. BA treatment resulted in significant
      decrease in sponge vascularization (Hb content) and in vascular endothelial
      growth factor (VEGF) and transforming growth factor (TGF-beta1) at both doses.
      Further, BA decreased expression of VEGF and CD31 and reduced % microvessel
      density (MVD) in sponge implants. A regulatory function of BA on multiple
      parameters of the main components of inflammatory angiogenesis has been revealed
      giving an insight into the potential therapeutic use underlying the actions of
      BA.

PMID- 21864544
TI  - Cross talk between focal adhesion kinase and cadherins: role in regulating
      endothelial barrier function.
AB  - A layer of endothelial cells attached to their underlying matrices by complex
      transmembrane structures termed focal adhesion (FA) proteins maintains the
      barrier property of microvascular endothelium. FAs sense the physical properties
      of the extracellular matrix (ECM) and organize the cytoskeleton accordingly. The
      close association of adherens junction (AJ) protein, cadherin, with the
      cytoskeleton is known to be essential in coordinating the appropriate mechanical
      properties to cell-cell contacts. Recently, it has become clear that a crosstalk
      exists between focal adhesion kinase (FAK) and cadherin that regulates signaling
      at intercellular endothelial junctions. This review discusses recent advances in
      our understanding of the dynamic regulation of the molecular connections between
      FAK and the cadherin complex and cadherin-catenin-actin interaction-dependent
      changes as well as the role of small GTPases in endothelial barrier regulation.
      This review also discusses how a signaling network regulates a range of cellular
      processes important for barrier function and diseases.

PMID- 21864546
TI  - Is there evidence of involvement of DNA repair polymorphisms in human cancer?
AB  - DNA suffers from a wide range of damage, both from extracellular agents and via
      endogenous mechanisms. Damage of DNA can lead to cancer and other diseases.
      Therefore, it is plausible that sequence variants in DNA repair genes are
      involved in cancer development. A recent systematic review and meta-analysis,
      based on the "Venice criteria", showed that out of 241 associations investigated,
      only three resulted to have a strong grade of cumulative evidence. These
      associations were: two SNPs rs1799793 and rs13181 in the ERCC2 gene and lung
      cancer (recessive model) and rs1805794 in the NBN gene and bladder cancer
      (dominant model). An update of this meta-analysis has been performed in the
      present paper, and we found partially inconsistent results. Inconsistencies in
      the literature are thus far not easy to explain. In addition, none of the cancer
      genome-wide association studies (GWAs) published so far showed highly
      statistically significant associations for any of the common DNA repair gene
      variants, in such a way as to place DNA repair genes among the top 10-20 hits
      identified in GWAs. Though this suggests that it is unlikely that DNA repair gene
      polymorphisms per se play a major role, a clarification of the discrepancies in
      the literature is needed. Also, gene/environment and gene/lifestyle interactions
      for the carcinogenic mechanisms involving DNA repair should be investigated more
      systematically and with less classification error. Finally, the combined effect
      of multiple SNPs in several genes in one or more relevant DNA repair pathways
      could have a greater impact on pathological phenotypes than SNPs in single genes,
      but this has been investigated only occasionally.

PMID- 21864547
TI  - Genetic mouse models relevant to schizophrenia: taking stock and looking forward.
AB  - Genetic mouse models relevant to schizophrenia complement, and have to a large
      extent supplanted, pharmacological and lesion-based rat models. The main
      attraction is that they potentially have greater construct validity; however,
      they share the fundamental limitations of all animal models of psychiatric
      disorder, and must also be viewed in the context of the uncertain and complex
      genetic architecture of psychosis. Some of the key issues, including the choice
      of gene to target, the manner of its manipulation, gene-gene and gene-environment
      interactions, and phenotypic characterization, are briefly considered in this
      commentary, illustrated by the relevant papers reported in this special issue.

PMID- 21864548
TI  - Isoflurane induces hippocampal cell injury and cognitive impairments in adult
      rats.
AB  - Post-operative cognitive dysfunction (POCD) is a clinical phenomenon
      characterized with cognitive decline in patients after anesthesia and surgery. It
      has been shown that interleukin-1beta (IL-1beta) contributes to the cognitive
      impairment of mice after surgery and isoflurane anesthesia. This study is
      designed to determine whether isoflurane alone increases inflammatory cytokines
      and causes cell injury and cognitive impairment. Four-month-old male Fisher 344
      rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. Two weeks
      later, rats were subjected to Barnes maze and fear conditioning tests. Although
      animals exposed to or non-exposed to isoflurane developed spatial learning,
      animals exposed to isoflurane had significant impairments in long-term spatial
      memory assessed by Barnes maze. They also had impaired hippocampus-dependent
      learning and memory in fear conditioning test. IL-1beta in the hippocampus was
      increased at 6 h after isoflurane exposure. Isoflurane also increased activated
      caspase 3 in the hippocampus and decreased the neuronal density in the CA1
      region. However, isoflurane did not change the amount of beta-amyloid peptide in
      the cerebral cortex at 29 days after isoflurane exposure when cognitive
      impairment was present. These results suggest that isoflurane increases
      inflammatory cytokine expression and causes cell injury in the hippocampus, which
      may contribute to isoflurane-induced cognitive impairment in rats.

PMID- 21864549
TI  - Establishing a learned-helplessness effect paradigm in C57BL/6 mice: behavioural
      evidence for emotional, motivational and cognitive effects of aversive
      uncontrollability per se.
AB  - Uncontrollability of major life events has been proposed to be central to
      depression onset and maintenance. The learned helplessness (LH) effect describes
      a deficit in terminating controllable aversive stimuli in individuals that
      experienced aversive stimuli as uncontrollable relative to individuals that
      experienced the same stimuli as controllable. The LH effect translates across
      species and therefore can provide an objective-valid readout in animal models of
      depression. Paradigms for a robust LH effect are established and currently
      applied in rat but there are few reports of prior and current study of the LH
      effect in mouse. This includes the C57BL/6 mouse, typically the strain of choice
      for application of molecular-genetic tools in pre-clinical depression research.
      The aims of this study were to develop a robust paradigm for the LH effect in
      BL/6 mice, provide evidence for underlying psychological processes, and study the
      effect of a depression-relevant genotype on the LH effect. The apparatus used for
      in/escapable electro-shock exposure and escape test was a two-way shuttle arena
      with continuous automated measurement of locomotion, compartment transfers, e
      shock escapes, vertical activity and freezing. Brother-pairs of BL/6 mice were
      allocated to either escapable e-shocks (ES) or inescapable e-shocks (IS), with
      escape latencies of the ES brother used as e-shock durations for the IS brother.
      The standard two-way shuttle paradigm was modified: the central gate was replaced
      by a raised divider and e-shock escape required transfer to the distal part of
      the safe compartment. These refinements yielded reduced superstitious, pre
      adaptive e-shock transfers in IS mice and thereby increased the LH effect. To
      obtain a robust LH effect in all brother pairs, pre-screening for minor between
      brother ES differences was necessary and did not confound the LH effect. IS mice
      developed reduced motor responses to e-shock, consistent with a motivational
      deficit, and absence of a learning curve for escapes at escape test, consistent
      with a cognitive deficit. When a tone CS was used to predict e-shock, IS mice
      exhibited increased reactivity to the CS, consistent with hyper-emotionality.
      There was no ES-IS difference in pain sensitivity. Mice heterozygous knockout for
      the 5-HTT gene exhibited an increased LH effect relative to wildtype mice. This
      mouse model will allow for the detailed molecular study of the aetiology,
      psychology, neurobiology and neuropharmacology of uncontrollability of aversive
      stimuli, a potential major aetiological factor and state marker in depression.
      This article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21864550
TI  - Emotionally negative stimuli can overcome attentional deficits in patients with
      visuo-spatial hemineglect.
AB  - Left unilateral spatial neglect resulting from right brain damage is
      characterized by loss of awareness for stimuli in the contralesional side of
      space, despite intact visual pathways. We examined using fMRI whether patients
      with neglect are more likely to consciously detect in the neglected hemifield,
      emotionally negative complex scenes rather than visually similar neutral pictures
      and if so, what neural mechanisms mediate this effect. Photographs of emotional
      and neutral scenes taken from the IAPS were presented in a divided visual field
      paradigm. As expected, the detection rate for emotional stimuli presented in the
      neglected field was higher than for neutral ones. Successful detection of
      emotional scenes as opposed to neutral stimuli in the left visual field (LVF)
      produced activations in the parahippocampal and anterior cingulate areas in the
      right hemisphere. Detection of emotional stimuli presented in the intact right
      visual field (RVF) activated a distributed network of structures in the left
      hemisphere, including anterior and posterior cingulate cortex, insula, as well as
      visual striate and extrastriate areas. LVF-RVF contrasts for emotional stimuli
      revealed activations in right and left attention related prefrontal areas whereas
      RVF-LVF comparison showed activations in the posterior cingulate and extrastriate
      visual cortex in the left hemisphere. An additional analysis contrasting detected
      vs. undetected emotional LVF stimuli showed involvement of left anterior
      cingulate, right frontal and extrastriate areas. We hypothesize that beneficial
      role of emotion in overcoming neglect is achieved by activation of frontal and
      limbic lobe networks, which provide a privileged access of emotional stimuli to
      attention by top-down modulation of processing in the higher-order extrastriate
      visual areas. Our results point to the importance of top-down regulatory role of
      the frontal attentional systems, which might enhance visual activations and lead
      to greater salience of emotional stimuli for perceptual awareness.

PMID- 21864551
TI  - Bilateral hand representations in human primary proprioceptive areas.
AB  - Sensory representations in the postcentral gyrus are supposed to be strictly
      lateralised and to provide spatially unbiased representations of limb positions.
      However, electrophysiological and behavioural measurements in humans and non
      human primates tentatively suggested some degree of bilateral processing even in
      early somatosensory areas. We report a patient who suffered a small and confined
      lesion of the hand area in the postcentral gyrus that resulted in a
      proprioceptive deficit without any concomitant primary motor impairment. We
      performed a finger position-matching task with target locations being defined
      proprioceptively. Without visual feedback of either hand, the patient
      demonstrated a significant leftward shift of perceived locations when reaching
      with the ipsilesional right hand to her contralesional left hand and an opposite
      rightward shift when reaching with the left hand to the position of the right
      hand. Although these directional errors improved when vision of the active hand
      was allowed, errors were still significantly larger than those of age-matched
      healthy controls with unconstrained view of the active contralesional hand.
      Reaching to visual targets without visual online feedback the patient revealed
      comparable errors with both hands. Reaching to visual targets with full visual
      feedback, she was as accurate as controls with either hand. In summary, our data
      demonstrate an effect of the right postcentral lesion on proprioceptive
      information processing for both hands. The results suggest an integration of
      contralateral and ipsilateral proprioceptive information already at this early
      processing stage possibly mediated by callosal connections.

PMID- 21864553
TI  - Effect of the dopamine D1-like receptor antagonist SCH 23390 on the
      microstructure of ingestive behaviour in water-deprived rats licking for water
      and NaCl solutions.
AB  - The analysis of licking microstructure provides measures, size and number of
      licking bouts, which might reveal, respectively, reward evaluation and
      behavioural activation. Based on the different effects of the dopamine D1-like
      and D2-like receptor antagonists SCH 23390 and raclopride on licking for sucrose,
      in particular the failure of the former to reduce bout size and the ability of
      the latter to induce a within-session decrement of bout number resembling either
      reward devaluation or neuroleptics on instrumental responding, we suggested that
      activation of reward-associated responses depends on dopamine D1-like receptor
      stimulation, and its level is updated on the basis of a dopamine D2-like receptor
      mediated reward evaluation. Consistent results were obtained in a study examining
      the effect of dopamine D2-like receptor antagonism in rats licking for NaCl
      solutions and water. In this study, we examined the effects of the dopamine D1
      like receptor antagonist SCH 23390 (0, 10, 20 and 40 MUg/kg) on the
      microstructure of licking for water and sodium chloride solutions (0.075 M, 0.15
      M, 0.3 M) in 12 h water deprived rats. Rats were exposed to each solution for 60
      s either after the first lick or after 3 min that the animals were placed in the
      chambers. Bout size, but not bout number, was decreased at the highest NaCl
      concentration. SCH 23390 produced a decrease of bout number and of lick number
      mainly due to the decreased number of subjects engaging in licking behaviour, and
      failed to reduce bout size for Na Cl and water at a dose which increased the
      latency to the 1st lick but did not affect the intra-bout lick rate. In agreement
      with previous observations, these results suggest that dopamine D1-like receptors
      play an important role in the activation of reward-oriented responses.

PMID- 21864552
TI  - Context-dependent encoding in the auditory brainstem subserves enhanced speech-in
      noise perception in musicians.
AB  - Musical training strengthens speech perception in the presence of background
      noise. Given that the ability to make use of speech sound regularities, such as
      pitch, underlies perceptual acuity in challenging listening environments, we
      asked whether musicians' enhanced speech-in-noise perception is facilitated by
      increased neural sensitivity to acoustic regularities. To this aim we examined
      subcortical encoding of the same speech syllable presented in predictable and
      variable conditions and speech-in-noise perception in 31 musicians and
      nonmusicians. We anticipated that musicians would demonstrate greater neural
      enhancement of speech presented in the predictable compared to the variable
      condition than nonmusicians. Accordingly, musicians demonstrated more robust
      neural encoding of the fundamental frequency (i.e., pitch) of speech presented in
      the predictable relative to the variable condition than nonmusicians. The degree
      of neural enhancement observed to predictable speech correlated with subjects'
      musical practice histories as well as with their speech-in-noise perceptual
      abilities. Taken together, our findings suggest that subcortical sensitivity to
      speech regularities is shaped by musical training and may contribute to
      musicians' enhanced speech-in-noise perception.

PMID- 21864554
TI  - Hydrogen peroxide signaling mediates DHEA-induced vascular endothelial cell
      proliferation.
AB  - Dehydroepiandrosterone (DHEA) activates a putative plasma membrane G(i)-protein
      coupled receptor to induce vascular endothelial proliferation. We now test the
      hypothesis that hydrogen peroxide (H(2)O(2)) signaling mediates this effect.
      Incubation of EA.hy926 cells, a human vascular endothelial cell line, with DHEA
      for 5 min produced a significant increase in H(2)O(2) production, measured by
      oxidation of either p-hydroxyphenylacetate or dichlorodihydrofluorescein. The
      DHEA effect on H(2)O(2) production was maximal at 1 nM DHEA, was evident within
      the first minute of incubation, and remained for 10 min. Similar results were
      present in primary bovine aortic endothelial cells. The induction of H(2)O(2) in
      EA.hy926 cells was mimicked by a membrane-impermeable albumin-conjugated DHEA and
      was inhibited by either catalase or pertussis toxin. Incubation of endothelial
      cells with DHEA for 5 min resulted in a 2-fold increase of cyclin D1 mRNA and
      protein expression at 4h. These effects were abolished by co-incubation with
      catalase. DHEA induced a 50 +/- 7% increase in cell proliferation over 24h,
      measured as cellular Ki-67 immunoreactivity. This proliferative effect was
      abolished by either catalase or pertussis toxin co-incubation, indicating an
      H(2)O(2) and G(i)-protein-dependent effect. We conclude that H(2)O(2) is a key
      signaling molecule mediating the proliferative effects of DHEA in vascular
      endothelial cells, possibly by up-regulating cell-cycle associated genes, such as
      cyclin D1.

PMID- 21864556
TI  - Polymorphic trial in oxidative damage of arsenic exposed Vietnamese.
AB  - Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes
      in the base excision repair (BER) pathway influence the generation and repair of
      oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine
      DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1)
      Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and
      Arg399Gln in the BER genes were analyzed, and the relationship between these 4
      SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100
      Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1
      326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did
      those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects
      showed significantly higher urinary 8-OHdG concentrations than did those
      homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic
      frequencies of the 4SNPs was performed in 10 population and previous reported
      data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations
      were higher than those in the African and Caucasian populations. As for APE1
      Asp148Glu, Caucasians showed higher mutant frequencies than those shown by
      African and Asian populations. Among Asian populations, the Bangladeshi
      population showed relatively higher mutant allele frequencies of the APE1
      Asp148Glu polymorphism. This study is the first to demonstrate the existence of
      genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1
      Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes.

PMID- 21864555
TI  - Sex-based differences in gene expression in hippocampus following postnatal lead
      exposure.
AB  - The influence of sex as an effect modifier of childhood lead poisoning has
      received little systematic attention. Considering the paucity of information
      available concerning the interactive effects of lead and sex on the brain, the
      current study examined the interactive effects of lead and sex on gene expression
      patterns in the hippocampus, a structure involved in learning and memory. Male or
      female rats were fed either 1500 ppm lead-containing chow or control chow for 30
      days beginning at weaning.Blood lead levels were 26.7+/-2.1 MUg/dl and 27.1+/-1.7
      MUg/dl for females and males, respectively. The expression of 175 unique genes
      was differentially regulated between control male and female rats. A total of 167
      unique genes were differentially expressed in response to lead in either males or
      females. Lead exposure had a significant effect without a significant difference
      between male and female responses in 77 of these genes. In another set of 71
      genes, there were significant differences in male vs. female response. A third
      set of 30 genes was differentially expressed in opposite directions in males vs.
      females, with the majority of genes expressed at a lower level in females than in
      males. Highly differentially expressed genes in males and females following lead
      exposure were associated with diverse biological pathways and functions. These
      results show that a brief exposure to lead produced significant changes in
      expression of a variety of genes in the hippocampus and that the response of the
      brain to a given lead exposure may vary depending on sex.

PMID- 21864557
TI  - Role of paraoxonase 1 (PON1) in organophosphate metabolism: implications in
      neurodegenerative diseases.
AB  - Organophosphate pesticides are a class of compounds that are widely used in
      agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is
      involved in the hydrolysis of organophosphate esters. Environmental poisoning by
      organophosphate compounds has been the main driving force of previous research on
      PON1 enzymes. Recent discoveries in animal models have revealed the important
      role of the enzyme in lipid metabolism. However although PON1 function is well
      established in experimental models, the contribution of PON1 in neurodegenerative
      diseases remains unclear. In this minireview we summarize the involvement of PON1
      genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and
      amyotrophic lateral sclerosis. A brief overview of latest epidemiological
      studies, regarding the two most important PON1 coding region polymorphisms PON1
      L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with
      disease occurrence are reported. Notably the MM and RR alleles contribute a risk
      enhancing effect for the development of some neurodegenerative diseases, which
      may be explained by the reduced lipoprotein free radical scavenging activity that
      may give rise to neuronal damage, through distinct mechanism. Conflicting
      findings that fail to support this postulate may represent the human population
      ethnic heterogeneity, different sample size and environmental parameters
      affecting PON1 status. We conclude that further epidemiological studies are
      required in order to address the exact contribution of PON1 genome in combination
      with organophosphate exposure in populations with neurodegenerative diseases.

PMID- 21864558
TI  - The relationship between peripapillary crescent and axial length: Implications
      for differential eye growth.
AB  - We evaluated the relationship between the size of the peripapillary crescent and
      the axial length (AL) of the eye as well as the fine structure of the
      peripapillary crescent in selected eyes. Infrared fundus imaging and spectral
      domain optical coherence tomography (SDOCT) (Spectralis HRA+OCT, Heidelberg
      Engineering, Germany) centered at the fovea were performed on 72 healthy adults.
      On the infrared fundus images, we measured (a) the distance between the foveola
      and the temporal edge of the optic disc (FOD) and (b) the distance between the
      foveola and the temporal edge of the peripapillary crescent (FOC) (if present). A
      peripapillary crescent presented at the nasal margin of the disc in 64% of the
      subjects. The FOD and FOC were 4.22mm+/-0.46 and 3.97mm+/-0.25, respectively.
      Only the FOD was significantly correlated with axial length. As AL increased by
      10%, the FOD increased by 13%, the outer neural retina only expanded by 4% (as
      indicated by the FOC). This result emphasizes that retinal stretching may not
      mirror scleral growth, and the existence in some eyes of a difference between the
      photoreceptor margin and retinal pigment epithelium (RPE) margin suggests that
      within the retina there could be slippage during eye growth.

PMID- 21864559
TI  - Exploring the time course of face matching: temporal constraints impair
      unfamiliar face identification under temporally unconstrained viewing.
AB  - The identification of unfamiliar faces has been studied extensively with matching
      tasks, in which observers decide if pairs of photographs depict the same person
      (identity matches) or different people (mismatches). In experimental studies in
      this field, performance is usually self-paced under the assumption that this will
      encourage best-possible accuracy. Here, we examined the temporal characteristics
      of this task by limiting display times and tracking observers' eye movements.
      Observers were required to make match/mismatch decisions to pairs of faces shown
      for 200, 500, 1000, or 2000ms, or for an unlimited duration. Peak accuracy was
      reached within 2000ms and two fixations to each face. However, intermixing
      exposure conditions produced a context effect that generally reduced accuracy on
      identity mismatch trials, even when unlimited viewing of faces was possible.
      These findings indicate that less than 2s are required for face matching when
      exposure times are variable, but temporal constraints should be avoided
      altogether if accuracy is truly paramount. The implications of these findings are
      discussed.

PMID- 21864560
TI  - Neural bases of selective attention in action video game players.
AB  - Over the past few years, the very act of playing action video games has been
      shown to enhance several different aspects of visual selective attention, yet
      little is known about the neural mechanisms that mediate such attentional
      benefits. A review of the aspects of attention enhanced in action game players
      suggests there are changes in the mechanisms that control attention allocation
      and its efficiency (Hubert-Wallander, Green, & Bavelier, 2010). The present study
      used brain imaging to test this hypothesis by comparing attentional network
      recruitment and distractor processing in action gamers versus non-gamers as
      attentional demands increased. Moving distractors were found to elicit lesser
      activation of the visual motion-sensitive area (MT/MST) in gamers as compared to
      non-gamers, suggestive of a better early filtering of irrelevant information in
      gamers. As expected, a fronto-parietal network of areas showed greater
      recruitment as attentional demands increased in non-gamers. In contrast, gamers
      barely engaged this network as attentional demands increased. This reduced
      activity in the fronto-parietal network that is hypothesized to control the
      flexible allocation of top-down attention is compatible with the proposal that
      action game players may allocate attentional resources more automatically,
      possibly allowing more efficient early filtering of irrelevant information.

PMID- 21864561
TI  - Switching dynamics of border ownership: a stochastic model for bi-stable
      perception.
AB  - A model that computes the border-ownership (BOWN) and the depth map of the image
      (DISC model, Kogo et al., 2010) is applied to investigate the stochastic nature
      of perception in "face or vase" stimuli. The 2-D integration of BOWN signals
      determines the figure-ground relationships in the image. In the present
      application of the model, BOWN signals are made stochastic and feedback
      connections are established between the higher level depth perception and the
      lower level BOWN signals. This feedback modifies the BOWN signals to further
      enhance the figure-ground segregation. Adaptation results in a decay of the
      response which leads to alternation. This triggers recovery of the adaptation.
      The alternation rate decreases in response to the increased levels of
      disambiguation. A detailed examination of the model parameters shows a
      prolongation of the alternation when the stimulus is presented intermittently in
      some conditions. In this framework, the adaptation and the recovery processes
      need to be perception dependent (not physical input dependent) to reproduce human
      perception.

PMID- 21864564
TI  - Chronic diseases, depressive symptoms and functional limitation amongst older
      people in rural Malaysia, a middle income developing country.
AB  - OBJECTIVES: To determine prevalence and prevalence ratio of functional limitation
      amongst older people with combined chronic diseases and co-morbid depressive
      symptoms compared with older people with either chronic disease or depressive
      symptoms alone. METHODS: Data were analysed from a cross-sectional study of 765
      people aged 60 years and over, conducted from 2007 to 2008 in Malaysia. Chronic
      diseases were self-reported, depressive symptoms were measured using the
      Geriatric Depression Scale and functional limitation was assessed using the
      Tinetti Performance Oriented Mobility Assessment Tool. RESULTS: A higher
      proportion of older people with combined chronic diseases and depressive symptoms
      reported having functional limitation (44.7%) compared with older people with
      chronic diseases alone (12.5%) and depressive symptoms alone (18.1%). Adjusting
      for socio-demographic characteristics, cognitive status and living arrangements,
      chronic diseases were associated with functional limitation (PR 2.21, 95% CI
      1.31, 3.72). Depressive symptoms were also associated with functional limitation
      (PR 2.07, 95% CI 1.56, 2.76). The prevalence ratio for functional limitation was
      much greater for combined chronic diseases and depressive symptoms (PR 4.09, 95%
      CI 2.23, 7.51). CONCLUSIONS: Older people with combined chronic diseases and
      depressive symptoms are more likely to have functional limitation than those with
      chronic disease or depressive symptoms alone.

PMID- 21864562
TI  - Assessment of a large panel of candidate biomarkers of ageing in the Newcastle
      85+ study.
AB  - Sensitive and specific biomarkers of ageing are needed to evaluate interventions
      to extend health span. However, there is growing evidence that information
      provided by candidate biomarkers may change with age itself. Little is yet known
      about the value of candidate biomarkers in those over 85 years, currently the
      fastest growing population sub-group in many countries. This study assessed a
      large panel of candidate biomarkers in a cohort of 85 years old by studying
      comparative associations with health status. Using a cross-sectional sample of
      852 individuals aged 85, we performed uni- and multi-variable analyses of
      associations between 74 candidate biomarkers and 4 health-status measures: viz.
      multi-morbidity, cognitive impairment, disability and proximity to death as
      measured by mortality within 1.5 years. We defined as most informative any
      measures that were significantly associated with at least two of the health
      status measures in multivariable analyses in this age group. 10 out of 74 tested
      candidates fulfilled this criterion, while several proposed biomarkers of ageing,
      notably inflammation and immune risk markers and telomere length, did not. As
      future data accrues on health outcomes within the cohort, it will become possible
      also to evaluate the predictive value of these and others of the candidate
      biomarkers.

PMID- 21864566
TI  - On causation in therapeutic research: observational studies, randomised
      experiments and instrumental variable analysis.
AB  - The counterfactual theory defines a conceptual framework for judging causation of
      therapeutic interventions. The main assumption underlying the claim that a
      counterfactual statement holds is that compared groups are exchangeable. In
      observational studies for therapeutic effects causal claims are hard to justify
      because the lack of exchangeability between compared groups. Randomised studies
      have a rather straightforward causal interpretation, based on the randomisation
      procedure that leads to expected exchangeability between compared groups. The use
      of instrumental variables can theoretically overcome the problems adherent to
      observational data, at least to a certain extent. The general idea of
      instrumental variables is to mimic a randomised trial, by searching for a
      variable that determines the probability of exposure (treatment) but that is not
      in other ways associated with the outcome under study. The assumptions for causal
      claims in IV analyses are strong, but the alternative of avoiding causal
      statements based on observational data, is less appealing.

PMID- 21864567
TI  - Polytobacco use in non-daily smokers: an issue requiring greater attention.

PMID- 21864568
TI  - Comparative analysis of malate synthase G from Mycobacterium tuberculosis and E.
      coli: role of ionic interaction in modulation of structural and functional
      properties.
AB  - Metabolic plasticity of Mycobacterium renders high degree of adaptive advantages
      in the persistence through the upregulation of glyoxylate shunt. The malate
      synthase (MS), an important enzyme of the shunt belongs to the G isoform and
      expressed predominantly as monomer. Here we did a comparative unfolding studies
      of two homologous MS from Mycobacterium tuberculosis (MtbMS) and Escherichia coli
      (ecMS) using various biophysical techniques. Despite having high sequence
      identities, they show different structural, stability and functional properties.
      The study suggests that the differences in the stability and unfolding of the two
      enzymes are by virtue of differential electrostatic modulation unique to their
      respective molecular assembly.

PMID- 21864569
TI  - Seroprevalence of antibodies to pertussis and diphtheria among healthy adults in
      China.
AB  - OBJECTIVES: Despite extensive childhood immunization, pertussis remains one of
      the world's leading causes of vaccine-preventable deaths. Incidence of pertussis
      in adolescents and adults has increased in many countries despite high
      vaccination coverage. In China, booster vaccinations against diphtheria, tetanus
      and pertussis are not used in adults, and little is known about pertussis
      incidence in the age group. The aim of this study was to determine seroprevalence
      of IgG antibodies to pertussis toxin (PT) and diphtheria among adults in China.
      METHODS: Blood samples were obtained from 210 healthy adults aged 18-50 years in
      Weifang city, China during the period of May and June 2010. Serum IgG antibodies
      against PT (anti-PT IgG) and diphtheria were determined by the commercial ELISA
      kits, respectively. According to the kit, concentration of anti-PT IgG higher
      than 30 IU/mL was considered positive. An antibody concentration of >= 0.1 IU/mL
      was defined as evidence of seroprotection against diphtheria. RESULTS: The mean
      concentration of anti-PT IgG antibodies was 9.95 IU/mL (95% confidence interval
      (CI) 8.45-11.44). Eleven (5.24%) of the studied subjects were proved to be
      seropositive to pertussis. Of the 210 subjects, 161 (76.6%) had anti-diphtheria
      antibody concentration >= 0.1 IU/mL and 49 (23.3%) had the antibody concentration
      between 0.01 and 0.099 IU/mL. CONCLUSIONS: Our study indicated that about 5% of
      adults aged 18-50 years had positive anti-PT IgG antibodies, suggesting that
      adult pertussis is not uncommon in China. Although a high proportion of studied
      subjects had a protective level of immunity against diphtheria, the antibody
      level decreased with the increasing age of adults. Booster vaccinations against
      pertussis should be considered in adults in China.

PMID- 21864570
TI  - Increasing incidence of necrotizing fasciitis in New Zealand: a nationwide study
      over the period 1990 to 2006.
AB  - OBJECTIVES: Because of concerns following necrotizing fasciitis (NF) reports in
      the media, we aimed to describe the incidence, mortality, case fatality and
      distribution of NF in New Zealand (NZ). METHODS: By using International
      Classification of Disease codes to identify NF cases we analyzed the national
      hospital discharge and mortality data and reviewed 299 charts from 8 hospitals.
      The sensitivity and positive predictive value (PPV) of the hospital discharge
      data were calculated by comparing with the mortality dataset and chart review
      finding respectively. RESULTS: Between 1990 and 2006 there was a highly
      significant rise in annual incidence and mortality rates of NF from 0.18 to 1.69
      and from 0 to 0.3 per 100,000 person-years respectively. The causes of this
      increase are unknown, and were not related to 2004 coding changes for NF.
      Hospital discharge data had a PPV of 82.6% and sensitivity of 76.8%. The case
      fatality was 20.8%. Disease risk was highest in the elderly, males, and Pacific
      and Maori populations. CONCLUSIONS: These findings suggest that incidence and
      mortality of NF are increasing in NZ. Further work is needed to investigate the
      causes of this increase and the marked ethnic inequalities in disease rates,
      particularly factors that may be preventable.

PMID- 21864571
TI  - Behaviour of Granger causality under filtering: theoretical invariance and
      practical application.
AB  - Granger causality (G-causality) is increasingly employed as a method for
      identifying directed functional connectivity in neural time series data. However,
      little attention has been paid to the influence of common preprocessing methods
      such as filtering on G-causality inference. Filtering is often used to remove
      artifacts from data and/or to isolate frequency bands of interest. Here, we show
      [following Geweke (1982)] that G-causality for a stationary vector autoregressive
      (VAR) process is fully invariant under the application of an arbitrary invertible
      filter; therefore filtering cannot and does not isolate frequency-specific G
      causal inferences. We describe and illustrate a simple alternative: integration
      of frequency domain (spectral) G-causality over the appropriate frequencies
      ("band limited G-causality"). We then show, using an analytically solvable
      minimal model, that in practice G-causality inferences often do change after
      filtering, as a consequence of large increases in empirical model order induced
      by filtering. Finally, we demonstrate a valid application of filtering in
      removing a nonstationary ("line noise") component from data. In summary, when
      applied carefully, filtering can be a useful preprocessing step for removing
      artifacts and for furnishing or improving stationarity; however filtering is
      inappropriate for isolating causal influences within specific frequency bands.

PMID- 21864572
TI  - Outer skull landmark-based coordinates for measurement of cerebral blood flow and
      intracranial pressure in rabbits.
AB  - Despite the increased use of intracranial neuromonitoring during experimental
      subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are
      lacking. This study evaluates the safety and reliability of using outer skull
      landmarks to identify locations for placement of cerebral blood flow (CBF) and
      intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was
      performed in 17 rabbits using an extracranial-intracranial shunt model. ICP
      probes were placed in the frontal lobe and compared to measurements recorded from
      the olfactory bulb. CBF probes were placed in various locations in the frontal
      cortex anterior to the coronary suture. Insertion depth, relation to the
      ventricular system, and ideal placement location were determined by post-mortem
      examination. ICP recordings at the time of SAH from the frontal lobe did not
      differ significantly from those obtained from the right olfactory bulb. Ideal
      coordinates for intraparenchymal CBF probes in the left and right frontal lobe
      were found to be located 4.6+/-0.9 and 4.5+/-1.2 anterior to the bregma, 4.7+/
      0.7mm and 4.7+/-0.5mm parasagittal, and at depths of 4+/-0.5mm and 3.9+/-0.5mm,
      respectively. The results demonstrate that the presented coordinates based on
      skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes
      in rabbit brains without the use of a stereotactic frame.

PMID- 21864573
TI  - A mathematical model of cell death in multiple sclerosis.
AB  - This paper imparts a mathematical model of multiple sclerosis (MS) that was
      created using Biochemical Systems Theory (BST). This method uses mechanisms and
      initial values from the literature to create a mathematical model of a disease.
      The model can then be used to test potential drug therapies and to detect
      possible trigger points for the disease. The focus of this MS model is mainly the
      action of reactive oxygen and nitrogen species (RONS), the permeability
      transition pore (PTP), apoptotic factors, and the eventual cell death in the
      oligodendrocyte. Several treatment methods were applied based on current
      therapies; however, one treatment, the prevention of the PTP from opening, is
      completely experimental and showed positive results based on this model. BST is
      an effective means of studying MS and can be beneficial in testing new therapy
      ideas.

PMID- 21864574
TI  - Transcranial electrical stimulation of cortico-cortical connections in
      anesthetized mice.
AB  - We developed a technique of transcranial electrical stimulation (TES) to
      investigate cortico-cortical connections in mice. After the skull was shaved with
      the blade of a dental bar, a blunt tip of a needle was gently pushed onto the
      thinned skull. The skull was deformed by the force, and the subarachnoid space
      between the skull and the cortex was minimized around the needle tip. Under these
      conditions, stimulus currents applied to the needle directly flowed into the
      cortex through the thinned skull. Cortico-cortical functional connections
      stimulated by this method were visualized by transcranial flavoprotein
      fluorescence imaging. The cortical responses evoked by TES exhibited spatial and
      temporal activity patterns comparable to those elicited by a conventional method,
      in which an electrode is directly inserted into superficial cortical layers. A
      comparison of the two methods revealed that TES required a slightly stronger
      stimulus intensity and preferentially activated superficial layers of the cortex
      compared with the conventional method. Using the new method, we revealed the
      presence of reciprocal cortico-cortical functional connections between lateral
      and medial parts of higher visual cortices in mice. This new method combined with
      transcranial flavoprotein fluorescence imaging allowed us to activate cortico
      cortical pathways arising from the primary sensory areas and investigate sensory
      information flow in the mouse cerebral cortex.

PMID- 21864575
TI  - A comparative analysis of intraperitoneal versus intracerebroventricular
      administration of bromodeoxyuridine for the study of cell proliferation in the
      adult rat brain.
AB  - Bromodeoxyuridine (BrdU) is the most widely used marker to detect proliferative
      cells in the adult brain. Here we analyse whether the route of administration of
      the tracer influences the number of labelled cells. For the intraperitoneal (ip)
      administration of BrdU, we performed two daily injections during 7 days, and for
      an intracerebroventricular (icv) delivery, it was continuously infused into one
      lateral ventricle for a 7 days period as well. After ip administration, cells
      labelled with BrdU were seen in the subventricular zone of the striatal wall of
      the lateral ventricle, the hippocampus and the neurohemal circumventricular
      organs. Also, the habenula and large myelinated tracts, such as the fornix and
      the corpus callosum, showed many BrdU-positive nuclei. Labelled nuclei were
      scarce in the parenchymal regions of the rest of the brain. In contrast, a
      significant increase in the number of BrdU-positive nuclei was observed in the
      parenchyma of the periventricular zones after icv administration of the marker,
      thus showing a greater availability of the tracer when it was administered
      directly into the ventricular cerebrospinal fluid. We suggest that the
      availability of BrdU in the vicinity of proliferating cells may depend on the
      permeability of the brain vessels to nucleosides in each location. By using
      double immunocytochemistry we found that neurons, astrocytes, oligodendrocytes,
      tanycytes and microglia had incorporated the tracer, demonstrating their
      proliferation capacity.

PMID- 21864577
TI  - Alternative cell types form a Multi-Component-Plasma-Cell-Niche.

PMID- 21864576
TI  - Mouse current vocalization threshold measured with a neurospecific nociception
      assay: the effect of sex, morphine, and isoflurane.
AB  - Sine-wave electrical stimulation at frequencies 2000, 250, and 5Hz to
      respectively evaluate Abeta, Adelta, and C sensory neurons has recently been
      added to the armamentarium used to evaluate sensory neurons. We developed an
      automated nociception assay using sine-wave stimulation methodology to determine
      current vocalization threshold in response to 2000, 250, and 5Hz and examine the
      effects of sex, analgesics, and anesthetics in mice. At baseline, males had
      significantly higher mean current vocalization thresholds compared with female
      mice at 2000, 250, and 5Hz (p<=0.019). By 1h after intrathecal injections of
      morphine there were significant increases in current vocalization threshold
      percent changes from baseline that varied with doses (p=0.0001) and frequency
      used (p<0.0001). Specifically, with increasing doses of morphine, there were
      significantly greater increases in current vocalization threshold percent changes
      from baseline in response to 5Hz compared with 250 and 2000Hz stimulation in a
      significantly ordered pattern: 5Hz>250Hz (p<0.0001) and 250Hz>2000Hz (p=0.0002).
      Forty-five minutes after exposure, there were no effects of isoflurane on current
      vocalization thresholds at any frequency. Therefore, our findings suggest that
      this automated nociception assay using sine-wave stimulation in mice, can be
      valuable for measurements of the effects of sex, opioids, and anesthetics on the
      response to electrical stimuli that preferentially stimulate Abeta, Adelta, and C
      sensory fibers in vivo. This investigation suggests the validation of this assay
      and supports its use to examine mechanisms of nociception in mice.

PMID- 21864578
TI  - Recombinant non-structural polyprotein 3AB-based serodiagnostic strategy for FMD
      surveillance in bovines irrespective of vaccination.
AB  - In India, the proportion of bovines vaccinated against foot-and-mouth disease
      (FMD) is increasing since the implementation of the Government supported 'FMD
      Control Programme', and non-structural protein (NSP)-based serological assays for
      discriminating between antibodies induced by infection or vaccination (DIVA)
      could be useful. The FMD virus NSP 3AB was expressed in a prokaryotic system and
      an indirect ELISA (r3AB(3) I-ELISA) was developed and validated as a screening
      assay for detecting virus in vaccinated bovines. The diagnostic sensitivity of
      the assay was estimated to be 96%, while the diagnostic specificity varied
      between the naive and vaccinates as 99.1% and 96.4%, respectively. This assay
      could detect antibodies to 3AB (3AB-Ab) from 10 to as late as 900 days post
      infection in cattle infected experimentally. The "in-house" assay demonstrated
      higher sensitivity than a commercial 3ABC ELISA kit particularly with samples
      obtained from the late stages of infection. Transient post-vaccinal 3AB-Ab
      response could be detected in one of the three commercial vaccines during the six
      month vaccination regimen, which emphasizes the fact that for a DIVA-compatible
      diagnostic strategy to be a realistic option, all vaccines need to be quality
      checked for the NSP content.

PMID- 21864579
TI  - Design and validation of consensus-degenerate hybrid oligonucleotide primers for
      broad and sensitive detection of corona- and toroviruses.
AB  - The ssRNA+ family Coronaviridae includes two subfamilies prototyped by
      coronaviruses and toroviruses that cause respiratory and enteric infections. To
      facilitate the identification of new distantly related members of the family
      Coronaviridae, we have developed a molecular assay with broad specificity. The
      consensus-degenerated hybrid oligonucleotide primer (CODEHOP) strategy was
      modified to design primers targeting the most conserved motifs in the RNA
      dependent RNA polymerase locus. They were evaluated initially on RNA templates
      from virus-infected cells using a two-step RT-PCR protocol that was further
      advanced to a one-step assay. The sensitivity of the assay ranged from 10(2) to
      10(6) and from 10(5) to 10(9) RNA copy numbers for individual corona-/torovirus
      templates when tested, respectively, with and without an excess of RNA from human
      cells. This primer set compared to that designed according to the original
      CODEHOP rules showed 10-10(3) folds greater sensitivity for 5 of the 6 evaluated
      corona-/torovirus templates. It detected 57% (32 of 56) of the respiratory
      specimens positive for 4 human coronaviruses, as well as stool specimens positive
      for a bovine torovirus. The high sensitivity and broad virus range of this assay
      makes it suitable for screening biological specimens in search for new viruses of
      the family Coronaviridae.

PMID- 21864580
TI  - A novel virus-encoded nucleocytoplasmic shuttling protein: the UL3 protein of
      herpes simplex virus type 1.
AB  - Herpes simplex virus type 1 (HSV-1) UL3 protein is a nuclear protein. In this
      study, the molecular mechanism of the subcellular localization of UL3 was
      characterized by fluorescence microscopy in living cells. A nuclear localization
      signal (NLS) and a nuclear export signal (NES) were also identified. UL3 was
      demonstrated to target to the cytoplasm through the NES via chromosomal region
      maintenance 1 (CRM-1) dependent pathway, and to the nucleus through RanGTP
      dependent mechanism. Heterokaryon assays confirmed that UL3 was capable of
      shuttling between the nucleus and the cytoplasm. These results demonstrate that
      the UL3 protein is a novel HSV-1 encoded nucleocytoplasmic shuttling protein.

PMID- 21864581
TI  - Central angiotensin converting enzyme facilitates memory impairment in
      intracerebroventricular streptozotocin treated rats.
AB  - Preclinical and clinical studies indicated involvement of renin angiotensin
      system (RAS) in memory functions. However, exact role of RAS in cognition is
      still ambiguous. Our aim was to explore how angiotensin converting enzyme (ACE)
      modulates memory in experimental model of memory impairment. Memory deficit was
      induced by intracerebroventricular administration of streptozotocin (STZ, 3mg/kg)
      in rats. Perindopril, an ACE inhibitor, was given for 21 days and memory function
      was evaluated by Morris water maze test. Cerebral blood flow (CBF) was measured
      by laser doppler flowmetry. The biochemical and expression studies were done in
      cortex and hippocampus of rat brain after the completion of behavioral studies.
      STZ caused impairment in memory along with significant reduction in CBF, ATP
      level and elevated oxidative and nitrosative stress. The activity and mRNA
      expression of acetylcholinesterase (AChE) and ACE were also increased in rat
      brain regions following STZ administration. However, serum ACE activity remained
      unaffected. Treatment with perindopril dose dependently improved memory by
      increasing energy metabolism and CBF. Perindopril also decreased oxidative and
      nitrosative stress, activity and mRNA expression of AChE and ACE in STZ treated
      rat. Further, ACE inhibition mitigated STZ induced neurodegeneration as observed
      in histopathological studies. Moreover, perindopril per se improved memory and
      CBF, decreased oxidative stress with no effect on AChE activity and expression.
      However, perindopril per se significantly reduced ACE activity but increased mRNA
      expression of ACE in rat brain. These results suggest that ACE occupies a pivotal
      role in STZ induced memory deficit thus implicating central RAS in cognition.

PMID- 21864582
TI  - Behavioral coping strategies in response to social stress are associated with
      distinct neuroendocrine, monoaminergic and immune response profiles in mice.
AB  - Individual variation in behavioral coping strategies to stress implies that
      animals may have a distinct physiological adaptation to stress; these differences
      may underlie differences in vulnerability to stress-related diseases. This study
      was designed to test the hypothesis that different behavioral coping strategies
      (active vs. passive) are stable over time and that they would be associated with
      differences in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adreno
      medular (SAM) axes, and monoaminergic and immune activity. Male mice were
      subjected to social stress. Twelve days after the first social interaction, mice
      were subjected to a second identical social stress interaction. Behavior was
      videotaped and assessed during both sessions. One hour after the final social
      interaction, serum was collected for corticosterone and adrenaline concentrations
      and brains were collected for hypothalamic corticotrophin-releasing hormone (CRH)
      mRNA expression. Monoaminergic system activity was determined by mRNA expression
      of serotonin, dopamine and noradrenaline synthetic enzymes in the brain stem.
      Immune system activity was determined by mRNA expression of hypothalamic
      interleukin-1beta (IL-1beta) and splenic IL-1beta and interleukin-2 (IL-2). Mice
      engaging in a passive strategy had higher serum corticosterone and lower serum
      adrenaline concentrations than the active group. The passive group showed lower
      hypothalamic mRNA expression of IL-1beta and CRH and lower splenic mRNA
      expression of IL-2 and IL-1beta relative to mice in the active group. An active
      strategy was associated with higher expression of the dopaminergic synthetic
      enzyme, while a passive strategy was associated with decreased expression of the
      serotonergic synthetic enzyme. These findings indicate that individual coping
      strategies are stable over time and are related to differences in the
      physiological stress response and immune activity.

PMID- 21864583
TI  - Zac1 functional interactions mediate AP-1 transcriptional activity.
AB  - A zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1) is
      a novel seven-zinc-finger protein that can bind a specific GC-rich DNA element
      and has intrinsic transactivation activity; therefore, its role as a
      transcription factor has been proposed. Zac1 not only promotes cell cycle arrest
      and apoptosis but also acts as a transcriptional cofactor for nuclear receptors
      and p53. In this study, we examined the functional roles of mouse Zac1 (mZac1) in
      HeLa cells treated with 12-O-tetradecanoylphorbol-13-acetate (PMA), a potent
      Activator protein 1 (AP-1) activator. At first, we found that mZac1 prolonged and
      enhanced PMA-induced AP-1 activity in both HeLa and HeLa/p53 shRNA cells. We
      further identified physical and functional interactions between mZac1 and AP-1
      proteins (either c-Jun, c-Fos or both). Finally, we showed that Zac1 might
      function as a selective coactivator of AP-1, demonstrated by AP-1-dependent
      transcriptional activation of collagenase, c-Fos and p21(WAF1/Cip1) promoter
      activities. Identification of AP-1 as a specific target for Zac1-mediated
      transcriptional events not only establishes a direct link between these two
      pivotal regulatory proteins but also raises the possibility that Zac1 contributes
      to certain AP-1-dependent biological effects.

PMID- 21864584
TI  - Sporulation studies in Clostridium difficile.
AB  - Clostridium difficile is a leading cause of healthcare-associated diarrhoea. In
      recent years, certain C. difficile types have become highly represented among
      clinical isolates and are associated with outbreaks of increased disease
      severity, higher relapse rates and an expanded repertoire of antibiotic
      resistance. Endospores, produced during sporulation, play a pivotal role in
      infection and disease transmission and it has been suggested in the literature
      that these so-called 'hypervirulent' C. difficile types are more prolific in
      terms of sporulation in vitro. However, work in our laboratory has provided
      evidence to the contrary suggesting that although there is significant strain-to
      strain variation in C. difficile sporulation characteristics this variation does
      not appear to be type-associated. On analysis of the literature, it is apparent
      that the methods used to quantify sporulation in previous studies have varied
      greatly and sample sizes have remained small. The conflicting data in the
      literature may, therefore, not necessarily be generally representative of C.
      difficile sporulation. Instead, these inconsistencies may reflect differences in
      the experimental design of each study. In this review, the need for further
      investigations of C. difficile sporulation rates is highlighted. Specifically,
      the advantages and disadvantages of the different experimental approaches
      previously used are discussed and a standard set of principles for measuring C.
      difficile sporulation in the future is proposed.

PMID- 21864585
TI  - Development of 3D architecture of uropathogenic Proteus mirabilis batch culture
      biofilms-A quantitative confocal microscopy approach.
AB  - This work studies the development of the 3D architecture of batch culture P.
      mirabilis biofilms on the basis of morpho-topological descriptors calculated from
      confocal laser scanning microscopy (CLSM) stacks with image processing routines.
      A precise architectonical understanding of biofilm organization on a morpho
      topological level is necessary to understand emergent interactions with the
      environment and the appearance of functionally different progeny swarmer cells.
      P. mirabilis biofilms were grown on glass coverslips for seven days on LB broth
      and subjected to in situ immunofluorescence. Confocal image stacks were
      deconvolved prior to segmentation of regions of interest (ROI) that identify
      individual bacteria and extracellular material, followed by 3D reconstruction and
      calculation of different morpho-topological key descriptors. Results showed that
      P. mirabilis biofilm formation followed a five stage process: (i) reversible
      adhesion to the surface characterized by slow growth, presence of elongated
      bacteria, and absence of extracellular material, (ii) irreversible bacterial
      adhesion concomitant to decreasing elongation, and the beginning of extracellular
      polymer production, (iii) accelerated bacterial growth concomitant to
      continuously decreasing elongation and halting of extracellular polymer
      production, (iv) maturation of biofilm defined by maximum bacterial density,
      volume, minimum elongation, maximum extracellular material, and highest
      compaction, and (v) decreased bacterial density and extracellular material
      through detachment and dispersion. Swarmer cells do not play a role in P.
      mirabilis biofilm formation under the applied conditions. Our approach sets the
      basis for future studies of 3D biofilm architecture using dynamic in vivo models
      and different environmental conditions that assess clinical impacts of P.
      mirabilis biofilm.

PMID- 21864586
TI  - RA-GEF-1 (Rapgef2) is essential for proper development of the midline
      commissures.
AB  - The cerebral hemispheres are directly connected by three major interhemispheric
      fibers: the corpus callosum, the anterior commissure, and the hippocampal
      commissure. RA-GEF-1 (also termed Rapgef2) is a guanine nucleotide exchange
      factor responsible for sustained activation of Rap1. We previously reported
      anatomical defects of the major forebrain commissures in the adult dorsal
      telencephalon-specific RA-GEF-1 conditional knockout (cKO) mice. In this study,
      we use neuroanatomical tracing and immunohistochemistry to study the formation of
      the commissural fibers during early postnatal development. DiI anterograde
      tracing reveals the inability of the callosal axons to cross the midline in cKO
      mice, thereby forming Probst bundles on the ipsilateral side, which is associated
      with the absence of the indusium griseum glia and the glial sling at the cortical
      midline. Wheat germ agglutinin-conjugated horseradish peroxidase retrograde
      tracing verifies the agenesis of the anterior commissure in cKO mice, and DiI
      anterograde tracing confirms the deviation of the fibers from their original
      tract. As for the hippocampal commissure, agenesis and hypoplasia are observed in
      its dorsal and ventral parts, respectively. These results indicate the essential
      role of RA-GEF-1 in the proper formation of the cerebral midline commissures.

PMID- 21864587
TI  - The development of a high-yield recombinant protein bioreactor through RNAi
      induced knockdown of ATP/ADP transporter in Solanum tuberosum.
AB  - There is an increased need for high-yield protein production platforms to meet
      growing demand. Tuber-based production in Solanum tuberosum offers several
      advantages, including high biomass yield, although protein concentration is
      typically low. In this work, we investigated the question whether minor
      interruption of starch biosynthesis can have a positive effect on tuber protein
      content and/or tuber biomass, as previous work suggested that partial obstruction
      of starch synthesis had variable effects on tuber yield. To this end, we used a
      RNAi approach to knock down ATP/ADP transporter and obtained a large number of
      transgenic lines for screening of lines with improved tuber protein content
      and/or tuber biomass. The initial screening was based on tuber biomass because of
      its relative simplicity. We identified a line, riAATP1-10, with minor (less than
      15%) reduction in starch, that had a nearly 30% increase in biomass compared to
      wild-type, producing both more and larger tubers with altered morphological
      features compared to wild-type. riAATP1-10 tubers have a higher concentration of
      soluble protein compared to wild-type tubers, with nearly 50% more soluble
      protein. We assessed the suitability of this line as a new bioreactor by
      expressing a human scFv, reaching over 0.5% of total soluble protein, a 2-fold
      increase over the highest accumulating line in a wild-type background. Together
      with increased biomass and increased levels in total protein content, foreign
      protein expression in riAATP1-10 line would translate into a nearly 4-fold
      increase in recombinant protein yield per plant. Our results indicate that
      riAATP1-10 line provides an improved expression system for production of foreign
      proteins.

PMID- 21864588
TI  - Fabrication of polyphenol biosensor based on laccase immobilized on copper
      nanoparticles/chitosan/multiwalled carbon nanotubes/polyaniline-modified gold
      electrode.
AB  - A high-performance amperometric polyphenol biosensor was developed, based on
      covalent immobilization of Ganoderma sp. laccase onto copper nanoparticles
      (CuNP's)/chitosan (CHIT)/carboxylated multiwalled carbon nanotube
      (cMWCNT)/polyaniline (PANI)-modified gold (Au) electrode. The CuNP's and cMWCNT
      had a synergistic electrocatalytic effect in the matrix of CHIT. The biosensor
      showed optimum response at pH 6.0 (0.1 M acetate buffer) and 35 degrees C, when
      operated at 50 mVs(-1). The biosensor exhibited excellent sensitivity (the
      detection limit was down to 0.156 MUM for guaiacol), fast response time (less
      than 4s) and wide linear range (from 1 to 500 MUM). Analytical recovery of added
      guaiacol was 96.40-98.46%. Within batch and between batch coefficients of
      variation were <2.6% and <5.3%, respectively. The enzyme electrode was used 300
      times over a period of 7 months, when stored at 4 degrees C.

PMID- 21864589
TI  - Persistence and the state of bovine and porcine adenoviral vector genomes in
      human and nonhuman cell lines.
AB  - The state of vector genome in transduced cells influences the duration of
      transgene expression and can be a safety concern if it gets integrated randomly
      into the host genome. Although human adenovirus (Ad) serotype 5 (HAd5) mainly
      persists in a linear episomal form, information regarding the state of bovine Ad
      serotype 3 (BAd3) and porcine Ad serotype 3 (PAd3) vector genomes in human and
      nonhuman cells is currently unknown. To address this issue, MDA-MB-231 (human),
      MDBK (bovine), PK-15 (porcine), MT1A2 (mouse) and NIH-3T3 (mouse) cell lines were
      infected with replication-defective BAd3, PAd3 or HAd5 vectors carrying the green
      fluorescent protein (GFP) gene. The persistence and the state of vector genome
      were assessed by quantitative real-time PCR and Southern blot hybridization,
      respectively. Levels of transgene and Ad gene expressions were quantified using
      real-time RT-PCR. Persistence of BAd3 or PAd3 vectors was comparable to that of
      HAd5 vector. Only the linear episomal form of the vector genome was observed with
      each vector. In addition, expression levels of transgene as well as viral genes
      by all three vectors were comparable and correlated with their transduction
      levels in each cell type. These results indicate comparable biologic behavior of
      BAd3, PAd3 and HAd5 vectors in cell culture.

PMID- 21864590
TI  - Induction of insert-specific immune response in mice by hamster polyomavirus VP1
      derived virus-like particles carrying LCMV GP33 CTL epitope.
AB  - Hamster polyomavirus (HaPyV) major capsid protein VP1 based chimeric virus-like
      particles (VLPs) carrying model GP33 CTL epitope derived from Lymphocytic
      choriomeningitis virus (LCMV) were generated in yeast and examined for their
      capability to induce CTL response in mice. Chimeric VP1-GP33 VLPs were
      effectively processed in antigen presenting cells in vitro and in vivo and
      induced antigen-specific CD8+ T cell proliferation. Mice immunized only once with
      VP1-GP33 VLPs without adjuvant developed an effective GP33-specific memory T cell
      response: 70% were fully and 30% partially protected from LCMV infection.
      Moreover, aggressive growth of tumors expressing GP33 was significantly delayed
      in these mice in vivo. Therefore, HaPyV VP1-derived VLP harboring CTL epitopes
      are attractive vaccine candidates for the induction of insert-specific CTL immune
      response.

PMID- 21864591
TI  - Intracerebral delivery of small interfering RNAs (siRNAs) using adenoviral vector
      protects mice against lethal peripheral rabies challenge.
AB  - To investigate the potential of RNA interference (RNAi) as antiviral agent
      against rabies, two small interfering RNAs (siRNAs) targeting rabies virus (RABV)
      nucleoprotein (N) and polymerase (L) genes were designed and evaluated. Both
      siRNAs knockdown or silenced the target RABV genes as evaluated in a plasmid
      based transient expression model. For efficient delivery, adenoviruses expressing
      the siRNAs were constructed and antiviral potential of the delivered siRNAs was
      investigated in BHK-21 cells. When cells treated with adenoviruses expressing
      siRNAs were challenged with RABV, there was 88.35+/-2.4% and 41.52+/-9.3%
      reduction in RABV multiplication in infected cells with siRNAs targeting RABV-N
      and L genes, respectively. Relative quantification of RABV transcripts using real
      time PCR revealed knockdown of both RABV-N and L gene transcripts, however,
      significant reduction was observed only with adenovirus expressing siRNA against
      RABV-N. When mice treated intracerebrally with adenoviruses expressing siRNAs
      were challenged peripherally with lethal RABV by the intramuscular route in
      masseter muscle, there was 66.6% and 33.3% protection with adenoviruses
      expressing siRNAs against RABV-N and L genes, respectively. These results
      demonstrated that adenovirus expressing siRNA against RABV-N efficiently
      inhibited the RABV multiplication both, in vitro and in vivo and conferred
      significant protection against lethal RABV challenge. This supported the
      hypothesis that RNAi, based on siRNA targeting RABV-N gene can prevent RABV
      infection and holds the potential of RNAi as an approach to prevent rabies
      infection.

PMID- 21864592
TI  - Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo
      evaluation of insulin-loaded formulations.
AB  - This work presents a new dry powder system consisting of microencapsulated
      protein-loaded chitosan nanoparticles (CS NPs). The developed system was
      evaluated in vivo in rats in order to investigate its potential to transport
      insulin (INS), a model protein, to the deep lung, where it is absorbed into
      systemic circulation. The INS-loaded CS NPs were prepared by ionotropic gelation
      and characterized for morphology, size, zeta potential, association efficiency
      and loading capacity. Afterwards, the NPs were co-spray dried with mannitol
      resulting in a dry powder with adequate aerodynamic properties for deposition in
      deep lungs. The assessment of the plasmatic glucose levels following
      intratracheal administration to rats revealed that the microencapsulated INS
      loaded CS NPs induced a more pronounced and prolonged hypoglycemic effect
      compared to the controls. Accordingly, the developed system constitutes a
      promising alternative to systemically deliver therapeutic macromolecules to the
      lungs, but it can also be used to provide a local effect.

PMID- 21864593
TI  - Nano-sized drug-loaded micelles deliver payload to lymph node immune cells and
      prolong allograft survival.
AB  - By delivering immunomodulatory drugs in vivo directly to lymph nodes draining an
      injection site, an opportunity exists to increase drug bioavailability to local
      immune cells. Importantly, particles smaller than 100 nm are efficiently
      transported through lymphatic vessels to draining lymph nodes. To investigate
      whether this approach could be used for local delivery of immunomodulatory drugs,
      amphiphilic poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) block
      copolymers forming 50 nm micelles were used to encapsulate hydrophobic drugs.
      Micelle drainage was determined using fluorescent micelles and showed effective
      targeting of multiple immune cell subsets in lymph nodes. For functional studies
      of our formulations, two approaches were considered. To evaluate the efficacy of
      anti-inflammatory drug delivery, dendritic cell activation was shown to be
      prevented when mice were pretreated with micelles loaded with the glucocorticoid
      mometasone and then challenged with the TLR9 ligand, CpG. To evaluate whether
      immunosuppressive drug-loaded micelles were effective in prolonging MHC
      mismatched allograft survival, BALB/c mice were treated for 14 consecutive days
      with drug-loaded micelles following transplantation of allogenic C57BL/6 tail
      skin. Micelles loaded with a mixture of rapamycin and tacrolimus prolonged
      allograft survival by 2-fold. Our results indicate that the drug-loaded micelle
      approach effectively targets the draining lymph nodes and exhibits proper immune
      regulation.

PMID- 21864594
TI  - Anthracycline-GnRH derivative bioconjugates with different linkages: synthesis,
      in vitro drug release and cytostatic effect.
AB  - To increase the selectivity and consequently to minimize the side effects of
      chemotherapeutic agents, receptor mediated tumor targeting approaches have been
      developed. In the present work, various anthracycline-GnRH derivative
      bioconjugates were synthesized with the aim of investigating the influence of (i)
      different anthracycline anticancer drugs, (ii) different linkages between the
      targeting moiety and the anticancer drug, and (iii) different targeting moieties
      (e.g., GnRH-III and [D-Lys6]-GnRH-I) on their in vitro drug release and
      cytostatic effect. The anthracyclines, daunorubicin or doxorubicin, were attached
      to the epsilon-amino group of Lys of GnRH-III or [D-Lys6]-GnRH-I through oxime,
      hydrazone or ester bonds. In another bioconjugate, a self-immolative p
      aminobenzyloxycarbonyl spacer was used to link daunorubicin to GnRH-III. The in
      vitro degradation of the bioconjugates was investigated in the presence of rat
      liver lysosomal homogenate and cathepsin B. The cellular uptake of the compounds
      was evaluated by flow cytometry and their in vitro cytostatic effect was
      determined by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.
      The results indicate that on the tested cancer cell lines there is no significant
      difference in the cellular uptake and in vitro cytostatic effect of bioconjugates
      containing GnRH-III or [D-Lys6]-GnRH-I as a targeting moiety. The bioconjugates
      containing ester bond, hydrazone bond and the self-immolative spacer exert the
      highest cytostatic effect, followed by oxime bond-linked compounds.

PMID- 21864595
TI  - Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics:
      modulation of encapsulation efficiency, release rate and lung deposition pattern
      by hydrophilic polymers.
AB  - Although few experimental studies have been handled so far to exploit the
      potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in the
      production of dry powders for antibiotic inhalation, there has been no
      comprehensive study on the role played by NP composition. In this work, we try to
      shed light on this aspect by designing and developing a pulmonary delivery system
      for antibiotics, such as tobramycin (Tb), based on PLGA NPs embedded in an inert
      microcarrier made of lactose, referred to as nano-embedded micro-particles (NEM).
      At nanosize level, helper hydrophilic polymers were used to impart the desired
      surface, bulk and release properties to PLGA NPs prepared by a modified emulsion
      solvent diffusion technique. Results showed that poly(vinyl alcohol) (PVA) and
      chitosan (CS) are essential to optimise the size and modulate the surface
      properties of Tb-loaded PLGA NPs, whereas the use of alginate (Alg) allows
      efficient Tb entrapment within NPs and its release up to one month. Optimized
      formulations display good in vitro antimicrobial activity against P. aeruginosa
      planktonic cells. Furthermore, spray-drying of the NPs with lactose yielded NEM
      with peculiar but promising flow and aerosolization properties, while preserving
      the peculiar NP features. Nonetheless, in vivo biodistribution studies showed
      that PVA-modified Alg/PLGA NPs reached the deep lung, while CS-modified NPs were
      found in great amounts in the upper airways, lining lung epithelial surfaces. In
      conclusion, PLGA NP composition appears to play a crucial role in determining not
      only the technological features of NPs but, once processed in the form of NEM,
      also their in vitro/in vivo deposition pattern.

PMID- 21864596
TI  - Nanoparticle mediated delivery of pure P53 supercoiled plasmid DNA for gene
      therapy.
AB  - The translation of non-viral gene replacement therapies for cancer into clinical
      application is currently hindered due to known issues associated with the
      effectiveness of plasmid DNA (pDNA) expression vectors and the production of gene
      delivery vehicles. Herein we report an integrative approach established on the
      synthesis of nanoparticulated carriers, in association with the supercoiled (sc)
      isoform purification of a p53 tumor suppressor encoding plasmid, to improve both
      delivery and transfection. An arginine-based chromatographic matrix with specific
      recognition for the different topoisoforms was used to completely isolate the
      biologically active sc pDNA. Our findings showed that the sc topoisoform is
      recovered under mild conditions with high purity and structural stability. In
      addition, to further enhance protection and transfection efficiency, the naked sc
      pDNA was encapsulated within chitosan nanoparticles by ionotropic gelation. The
      mild conditions for particle synthesis used in the former technique allowed the
      attainment of a high encapsulation efficiency for sc pDNA (>75%). Moreover, in
      vitro transfection experiments confirmed the reinstatement of the p53 protein
      expression and most importantly, the sc pDNA transfected cells exhibited the
      highest p53 expression levels when compared to other formulations. Overall, given
      the fact that sc pDNA topoisoform indeed enhances transgene expression rates this
      approach might have a profound impact on the development of a sustained nucleic
      acid-based therapy for cancer.

PMID- 21864597
TI  - Design of an inhalable dry powder formulation of DOTAP-modified PLGA
      nanoparticles loaded with siRNA.
AB  - Matrix systems based on biocompatible and biodegradable polymers like the United
      States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co
      glycolide acid) (PLGA) are promising for the delivery of small interfering RNA
      (siRNA) due to favorable safety profiles, sustained release properties and
      improved colloidal stability, as compared to polyplexes. The purpose of this
      study was to design a dry powder formulation based on cationic lipid-modified
      PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary
      delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP)
      was incorporated into the PLGA matrix to potentiate the gene silencing
      efficiency. The gene knock-down level in vitro was positively correlated to the
      weight ratio of DOTAP in the particles, and 73% silencing was achieved in the
      presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for
      nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression
      with 54%. This formulation was spray-dried with mannitol into nanocomposite
      microparticles of an aerodynamic size appropriate for lung deposition. The spray
      drying process did not affect the physicochemical properties of the readily re
      dispersible nanoparticles, and most importantly, the in vitro gene silencing
      activity was preserved during spray-drying. The siRNA content in the powder was
      similar to the theoretical loading and the siRNA was intact, suggesting that the
      siRNA is preserved during the spray-drying process. Finally, X-ray powder
      diffraction analysis demonstrated that mannitol remained in a crystalline state
      upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient
      might exert its stabilizing effect by sterical inhibition of the interactions
      between adjacent nanoparticles. This study demonstrates that spray-drying is an
      excellent technique for engineering dry powder formulations of siRNA
      nanoparticles, which might enable the local delivery of biologically active siRNA
      directly to the lung tissue.

PMID- 21864598
TI  - Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for
      the HIV-1 entry inhibitor maraviroc.
AB  - Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose
      (HEC) and polyacrylic acid (e.g. Carbopol(r)), have a long history of use in
      vaginal drug delivery. However, despite their ubiquity, they often provide sub
      optimal clinical performance, due to poor mucosal retention and limited
      solubility for poorly water-soluble actives. These issues are particularly
      pertinent for vaginal HIV microbicides, since many lead candidates are poorly
      water-soluble and where a major goal is the development of a coitally
      independent, once daily gel product. In this study, we report the use of a non
      aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor
      maraviroc. In vitro rheological, syringeability and retention studies
      demonstrated enhanced performance for silicone gels compared with a conventional
      aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of
      mucosal irritancy. Pharmacokinetic studies following single dose vaginal
      administration of a maraviroc silicone gel in rhesus macaques showed higher and
      sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a
      HEC gel containing the same maraviroc loading. The results demonstrate that non
      aqueous silicone gels have potential as a formulation platform for coitally
      independent vaginal HIV microbicides.

PMID- 21864599
TI  - Octaarginine- and pH sensitive fusogenic peptide-modified nanoparticles for liver
      gene delivery.
AB  - We previously reported that octaarginine peptide modified liposomes (R8
      liposomes) largely accumulated in the liver after intravenous administration and
      that this is dependent on the R8-density. We report herein on the development of
      a Multifunctional Envelope-type Nano Device modified with R8 and GALA, as a pH
      sensitive fusogenic peptide (R8-GALA-MEND) for liver gene delivery. An R8-MEND
      encapsulating pDNA prepared using two different cores (negatively or positively
      charged pDNA/polyethylene imine condensed particles) failed to produce a high
      gene expression in the liver. Modification with GALA dramatically increased gene
      expression particularly in the liver only in the case of a negative core R8-MEND.
      Quantification of the number of gene copies delivered to liver cells and nuclei
      revealed that the amount of pDNA was significantly higher in the case of positive
      core R8-MENDs, regardless of the absence or presence of GALA. However, gene
      expression efficiencies per nucleus-delivered pDNA were much higher in the case
      of the negative core R8-MEND, especially the R8-GALA-MEND suggesting that the
      substantial improvement in gene expression can be explained by an improved gene
      expression efficiency per pDNA in the presence of GALA. A comparative study
      between the developed R8-GALA-MEND and a similar system containing DOTAP, a
      commonly used cationic lipid, instead of R8 showed that gene expression of the R8
      GALA-MEND was 29 times higher than that of the DOTAP-GALA-MEND and is more
      selective for the liver. Collectively, these results suggest that the combination
      of a negatively charged core system and GALA modification of the R8-MEND is
      useful system for efficiently delivering genes to the liver.

PMID- 21864600
TI  - Watching food-related television increases caloric intake in restrained eaters.
AB  - While watching 30-min television (TV) programs that contained either food-related
      content or non-food-related content, participants were asked to eat two types of
      candy by explicitly being told that we were interested in how the TV program
      influenced their taste and therefore they needed to consume some of those
      candies. The results indicated that there was no overall difference in candy
      intake based on the TV content; however, the association was moderated by their
      restrained eating status. Restrained eaters ate more calories while watching a
      food-related TV program whereas unrestrained eaters were not influenced by the
      content of the TV program.

PMID- 21864601
TI  - Body weight relationships in early marriage. Weight relevance, weight
      comparisons, and weight talk.
AB  - This investigation uncovered processes underlying the dynamics of body weight and
      body image among individuals involved in nascent heterosexual marital
      relationships in Upstate New York. In-depth, semi-structured qualitative
      interviews conducted with 34 informants, 20 women and 14 men, just prior to
      marriage and again one year later were used to explore continuity and change in
      cognitive, affective, and behavioral factors relating to body weight and body
      image at the time of marriage, an important transition in the life course. Three
      major conceptual themes operated in the process of developing and enacting
      informants' body weight relationships with their partner: weight relevance,
      weight comparisons, and weight talk. Weight relevance encompassed the changing
      significance of weight during early marriage and included attracting and
      capturing a mate, relaxing about weight, living healthily, and concentrating on
      weight. Weight comparisons between partners involved weight relativism, weight
      competition, weight envy, and weight role models. Weight talk employed pragmatic
      talk, active and passive reassurance, and complaining and critiquing criticism.
      Concepts emerging from this investigation may be useful in designing future
      studies of and approaches to managing body weight in adulthood.

PMID- 21864602
TI  - Synthetic peptides from two Pf sporozoite invasion-associated proteins
      specifically interact with HeLa and HepG2 cells.
AB  - Two recently described molecules have been associated with sporozoite traversal
      ability and hepatocyte entry: sporozoite invasion-associated proteins (SIAP)-1
      and -2. The HeLa and HepG2 cell binding ability of synthetic peptides spanning
      the whole SIAP-1 and -2 sequences has been studied in the search for identifying
      these proteins' functionally active specific regions. Twelve HepG-2 and seventeen
      HeLa cell high-activity binding peptides (HABPs) have been identified in SIAP-1,
      8 of them having high specific binding affinity for both cell lines. Four HepG2
      HABPs and two HeLa HABPs have been identified in SIAP-2, one of them interacting
      with both HeLa and HepG2 cells. SIAP-1 and SIAP-2 HABPs bound specifically and
      saturably to heparin sulfate and chondroitin sulfate-type membrane receptors on
      host cells. Circular dichroism assays have shown high alpha-helix content in SIAP
      1 and SIAP-2 HABP secondary structure. Immunofluorescence analysis has revealed
      that specific peptides against SIAP proteins are highly immunogenic in mice and
      that anti-SIAP-1 and -2 antibodies recognize the native protein in Plasmodium
      falciparum sporozoites. Polymorphism studies have shown that a most SIAP-1 and -2
      HABPs are conserved among P. falciparum strains. Our results have suggested that
      SIAP-1 and -2 participate in host-pathogen interactions during cell-traversal and
      hepatocyte invasion and highlighted the relevance of the ongoing identification
      and study of potentially new molecules when designing a fully protective
      antimalarial vaccine.

PMID- 21864603
TI  - Inhibitory effect of corticotropin-releasing factor on food intake in the
      bullfrog, Aquarana catesbeiana.
AB  - Corticotropin-releasing factor (CRF) and CRF-related peptides exert
      hypophysiotropic and anorexigenic effects in mammals and teleost fish. In anuran
      amphibians, CRF acts as a potent stimulator of thyrotropin release from the
      pituitary. According to our recent study, CRF also acts as an anorexigenic factor
      for the cessation of food intake in the metamorphosing bullfrog larvae. However,
      the anorexigenic action of CRF has not been confirmed in adult bullfrogs. In this
      context, we examined the effect of feeding status on the expression level of the
      CRF transcript in the hypothalamus of the adult bullfrog. Levels of CRF mRNA in
      the hypothalami from bullfrogs fasted for 7 days were lower than in those from
      the bullfrogs that had been fed normally. Subsequently, we developed a method for
      measuring food intake in adult bullfrogs, and then investigated the effect of CRF
      on their food consumption in these animals. Intracerebroventricular (ICV)
      administration of CRF at 1 and 10pmol/g body weight (BW) induced a significant
      decrease of food intake during 60min. The CRF-induced anorexigenic action was
      blocked by treatment with a CRF receptor 1/CRF receptor 2 antagonist, alpha
      helical CRF((9-41)), at 100pmol/g BW. These results provide direct evidence for
      the inhibitory effect of CRF on food intake, and suggest the involvement of CRF
      in the regulation of feeding through a CRF receptor-signaling pathway in the
      adult bullfrog.

PMID- 21864604
TI  - Sequencing and biological effects of an adipokinetic/hypertrehalosemic peptide in
      the stick insect, Baculum extradentatum.
AB  - The corpora cardiaca of the Vietnamese stick insect, Baculum extradentatum,
      contain a member of the adipokinetic hormone/red pigment-concentrating
      hormone/hypertrehalosemic hormone (AKH/RPCH/HrTH) family of peptides whose
      sequence is identical to that originally described for the Indian stick insect,
      Carausius morosus. This decapeptide, Carmo-HrTH-II (pELTFTPNWGTa), has both
      hypertrehalosemic and cardioacceleratory activity in B. extradentatum, and
      hyperlipaemic activity in locusts. Reversed-phase high performance liquid
      chromatography (RP-HPLC) of corpora cardiaca extract followed by MALDI-TOF MS/MS
      also revealed a novel modification of a second peptide in B. extradentatum: the
      tryptophan residue at position 8 is post-translationally modified to kynurenine.

PMID- 21864605
TI  - Isolation and characterization of peptide antibiotics LI-F04 and polymyxin B6
      produced by Paenibacillus polymyxa strain JSa-9.
AB  - Paenibacillus polymyxa JSa-9 had been found to produce five cyclic LI-F type
      antibiotics which were released into culture medium in accordance with our
      previous report. In this study, another three kinds of antagonistic compounds
      were extracted from P. polymyxa JSa-9 cell pellets and (or) spores by methanol.
      Using high performance liquid chromatography (HPLC) method, two antagonistic
      fractions were separated and collected from the methanol extract. One showed
      inhibition against Escherichia coli and Staphylococcus aureus, while the other
      was active against Aspergillus niger and S. aureus. By means of electrospray
      ionization mass spectroscopy (ESI-MS), infrared spectroscopy (IR), and amino acid
      analysis, two kinds of compounds from fraction B with molecular masses of 901 and
      915Da were characterized as the linear lipopeptide analogs of antibiotics LI-F04a
      and LI-F04b, respectively. Another antimicrobial substance from fraction A could
      be attributed to polymyxin B(6).

PMID- 21864606
TI  - Identifying the regulatory element for human angiotensin-converting enzyme 2
      (ACE2) expression in human cardiofibroblasts.
AB  - Angiotensin-converting enzyme 2 (ACE2) has been proposed as a potential target
      for cardioprotection in regulating cardiovascular functions, owing to its key
      role in the formation of the vasoprotective peptides angiotensin-(1-7) from
      angiotensin II (Ang II). The regulatory mechanism of ace2 expression, however,
      remains to be explored. In this study, we investigated the regulatory element
      within the upstream of ace2. The human ace2 promoter region, from position -2069
      to +20, was cloned and a series of upstream deletion mutants were constructed and
      cloned into a luciferase reporter vector. The reporter luciferase activity was
      analyzed by transient transfection of the constructs into human cardiofibroblasts
      (HCFs) and an activating domain was identified in the -516/-481 region. Deletion
      or reversal of this domain within ace2 resulted in a significant decrease in
      promoter activity. The nuclear proteins isolated from the HCFs formed a DNA
      protein complex with double stranded oligonucleotides of the -516/-481 domain, as
      detected by electrophoretic mobility shift assay. Site-directed mutagenesis of
      this region identified a putative protein binding domain and a potential binding
      site, ATTTGGA, homologous to that of an Ikaros binding domain. This regulatory
      element was responsible for Ang II stimulation via the Ang II-Ang II type-1
      receptor (AT1R) signaling pathway, but was not responsible for pro-inflammatory
      cytokines TGF-beta1 and TNF-alpha. Our results suggest that the nucleotide
      sequences -516/-481 of human ace2 may be a binding domain for an as yet
      unidentified regulatory factor(s) that regulates ace2 expression and is
      associated with Ang II stimulation.

PMID- 21864607
TI  - Up-regulation of apelin in brain tissue of patients with epilepsy and an
      epileptic rat model.
AB  - Prolonged epileptic seizures or SE can cause neuronal cell death. However, the
      exact role of neuroprotectant against brain injury during epileptic seizure needs
      to be further elucidated. The aim of this study was to investigate the expression
      of the apelin, a novel neuroprotective peptide, in brain tissues of the patients
      with temporal lobe epilepsy (TLE) and experimental rats using
      immunohistochemistry, immunofluorescence and Western blotting analysis and to
      discuss the possible role of apelin in TLE. Thirty temporal neocortical tissue
      samples from the patients with drug-refractory TLE underwent surgical therapy and
      nine histologically normal temporal lobes tissues as controls were used in our
      study. Fifty-six Sprague-Dawley rats were randomly divided into seven groups,
      including one control group and six groups with epilepsy induced by lithium
      pilocarpine. Hippocampus and adjacent cortex were taken from the controls and
      epileptic rats at 1, 3, 7, 14, 30, and 60 days after onset of seizures. Apelin
      was mainly expressed in the neurons of TLE patients and controls, and was
      significantly increased in TLE patients compared with the controls. Apelin was
      also expressed in the neurons of experimental and control rats, it was gradually
      increased in the experimental rat post-seizure and reached a stable high level in
      chronic epileptic phase. Our results demonstrated that the increased expression
      of apelin in the brain may be involved in human TLE.

PMID- 21864608
TI  - Mitochondrial ERK plays a key role in delta-opioid receptor neuroprotection
      against acute mitochondrial dysfunction.
AB  - It is well established that stimulating delta-opioid receptor (DOR) with its
      specific agonists elicits neuroprotection against hypoxia/ischemia. Mitochondrial
      dysfunction plays a key role in hypoxic neuronal injury, but the effects of DOR
      activation on mitochondrial dysfunction in neurons are poorly elucidated. In this
      investigation, we studied the effects of [D-Ala2, D-Leu5] enkephalin (DADLE), a
      potent DOR agonist, on acute mitochondrial dysfunction and ensuing cell damage
      induced by sodium azide in primary rat cortical neuronal cultures, and explored
      possible mechanisms underlying. Here, we show that DADLE reverses NaN(3)-induced
      acute mitochondrial dysfunction by selectively activating DOR, mainly including
      mitochondrial membrane depolarization, mitochondrial Ca(2+) overload and reactive
      oxygen species generation. DOR stimulation also inhibits cytochrome c release and
      caspase-3 activation, and attenuates neuronal death caused by acute NaN(3)
      insults. Furthermore, DOR activation with DADLE protects neurons from acute
      NaN(3) insults mainly through PKC-ERK pathway, and mitochondrial ERK activation
      is especially required for DOR neuroprotection against acute mitochondrial
      dysfunction.

PMID- 21864609
TI  - Neuroinflammation in acute liver failure: mechanisms and novel therapeutic
      targets.
AB  - It is increasingly evident that neuroinflammatory mechanisms are implicated in
      the pathogenesis of the central nervous system (CNS) complications (intracranial
      hypertension, brain herniation) of acute liver failure (ALF). Neuroinflammation
      in ALF is characterized by microglial activation and arterio-venous difference
      studies as well as studies of gene expression confirm local brain production and
      release of proinflammatory cytokines including TNF-alpha and the interleukins IL
      1beta and IL-6. Although the precise nature of the glial cell responsible for
      brain cytokine synthesis is not yet established, evidence to date supports a role
      for both astrocytes and microglia. The neuroinflammatory response in ALF
      progresses in parallel with the progression of hepatic encephalopathy (HE) and
      with the severity of brain edema (astrocyte swelling). Mechanisms responsible for
      the relaying of signals from the failing liver to the brain include transduction
      of systemic proinflammatory signals as well as the effects of increased brain
      lactate leading to increased release of cytokines from both astrocytes and
      microglia. There is evidence in support of a synergistic effect of
      proinflammatory cytokines and ammonia in the pathogenesis of HE and brain edema
      in ALF. Therapeutic implications of the findings of a neuroinflammatory response
      in ALF are multiple. Removal of both ammonia and proinflammatory cytokines is
      possible using antibiotics or albumen dialysis. Mild hypothermia reduces brain
      ammonia transfer, brain lactate production, microglial activation and
      proinflammatory cytokine production resulting in reduced brain edema and
      intracranial pressure in ALF. N-Acetylcysteine acts as both an antioxidant and
      anti-inflammatory agent at both peripheral and central sites of action
      independently resulting in slowing of HE progression and prevention of brain
      edema. Novel treatments that directly target the neuroinflammatory response in
      ALF include the use of etanercept, a TNF-alpha neutralizing molecule and
      minocycline, an agent with potent inhibitory actions on microglial activation
      that are independent of its antimicrobial properties; both agents have been shown
      to be effective in reducing neuroinflammation and in preventing the CNS
      complications of ALF. Translation of these findings to the clinic has the
      potential to provide rational targeted approaches to the prevention and treatment
      of these complications in the near future.

PMID- 21864611
TI  - The +874T/A polymorphism in the interferon-gamma gene and tuberculosis risk: an
      update by meta-analysis.
AB  - The +874T/A polymorphism in the interferon-gamma (IFN-gamma) gene has been
      extensively examined for association to tuberculosis (TB); however, results of
      different studies have been inconsistent. The aim of this study was to
      comprehensively analyze the genetic risk of the +874T/A polymorphism in IFN-gamma
      gene for TB by meta-analysis. A total of 4553 cases and 4631 controls in 21 case
      control studies were included in this meta-analysis. The results indicated that
      the variant T allele carriers had a 27% decreased risk of TB, when compared with
      the homozygote AA (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.61
      0.87 for TT + TA versus AA). In the subgroup analysis by ethnicity, significant
      decreased risks were associated with T allele carriers in Asians (OR= 0.71, 95%
      CI = 0.52-0.97, p = 0.03) but not in Caucasians (OR = 0.87, 95% CI = 0.65-1.17, p
      = 0.37). Our results suggest that the IFN-gamma +874T/A polymorphism contributes
      to susceptibility to TB.

PMID- 21864610
TI  - PKCbeta-dependent phosphorylation of the glycine transporter 1.
AB  - The extracellular levels of the neurotransmitter glycine in the brain are tightly
      regulated by the glycine transporter 1 (GlyT1) and the clearance rate for glycine
      depends on its rate of transport and the levels of cell surface GlyT1. Over the
      years, it has been shown that PKC tightly regulates the activity of several
      neurotransmitter transporters. In the present work, by stably expressing three N
      terminus GlyT1 isoforms in porcine aortic endothelial cells and assaying for
      [(32)P]-orthophosphate metabolic labeling, we demonstrated that the isoforms
      GlyT1a, GlyT1b, and GlyT1c were constitutively phosphorylated, and that
      phosphorylation was dramatically enhanced, in a time dependent fashion, after PKC
      activation by phorbol ester. The phosphorylation was PKC-dependent, since pre
      incubation of the cells with bisindolylmaleimide I, a selective PKC inhibitor,
      abolished the phorbol ester-induced phosphorylation. Blotting with specific anti
      phospho-tyrosine antibodies did not yield any signal that could correspond to
      GlyT1 tyrosine phosphorylation, suggesting that the phosphorylation occurs at
      serine and/or threonine residues. In addition, a 23-40%-inhibition on V(max) was
      obtained by incubation with phorbol ester without a significant change on the
      apparent Km value. Furthermore, pre-incubation of the cells with the selective
      PKCalpha/beta inhibitor Go6976 abolished the downregulation effect of phorbol
      ester on uptake and phosphorylation, whereas the selective PKCbeta inhibitors
      (PKCbeta inhibitor or LY333531) prevented the phosphorylation without affecting
      glycine uptake, defining a specific role of classical PKC on GlyT1 uptake and
      phosphorylation. Taken together, these data suggest that conventional
      PKCalpha/beta regulates the uptake of glycine, whereas PKCbeta is responsible for
      GlyT1 phosphorylation.

PMID- 21864612
TI  - Healthy-days time equivalents for outcomes of acute rotavirus infections.
AB  - Rotavirus is the most common cause of severe gastroenteritis in infants and young
      children worldwide. Health-state utility measures used in economic evaluations of
      rotavirus vaccines do not reflect differences between mild and severe symptoms of
      rotavirus gastroenteritis and, therefore, do not adequately capture preferences
      for non-fatal outcomes associated with rotavirus common in industrialized
      countries. This paper describes the development and results of a survey
      specifically designed to develop quality-adjusted time equivalents for rotavirus
      gastroenteritis among a sample of parents with young children in the United
      States as an alternative to conventional QALY measures in assessing cost
      effectiveness.

PMID- 21864613
TI  - Immunogenicity and safety of a single intramuscular dose of a diphtheria-tetanus
      toxoid (Td) vaccine (GC1107) in Korean adults.
AB  - The current study aimed to evaluate immunogenicity and safety of a newly
      developed diphtheria-tetanus toxoid (Td) vaccine, GC1107 (Green Cross
      Corporation, Yongin, Korea), in comparison with placebo and active comparator
      (licensed Td vaccine) in healthy Korean adults. A randomized, double-blind,
      placebo and active comparator-controlled study was conducted. Forty subjects were
      randomly administered a single intramuscular dose of GC1107, active comparator or
      placebo in a ratio of 2:1:1. At 2 and 4 weeks after vaccination, anti-diphtheria
      antibody levels in the GC1107 group increased 9.2 and 9.3 times, respectively,
      compared to predose titers. The corresponding values were 9.3 and 8.3 times for
      the active comparator group. Anti-tetanus antibody levels increased 39.0 and 37.9
      fold at 2 and 4 weeks, respectively, after GC1107 administration, and 12.2 and
      14.7 fold after active comparator administration. No increases in tetanus or
      diphtheria antibody were observed for the placebo group. Adverse events in the
      GC1107 and active comparator groups were more frequent than for the placebo
      group, but there were no significant differences between the two active
      treatments. In conclusion, GC1107 was well tolerated and provided significant
      boosts of anti-tetanus and anti-diphtheria antibodies.

PMID- 21864614
TI  - Increase in viral yield in eggs and MDCK cells of reassortant H5N1 vaccine
      candidate viruses caused by insertion of 38 amino acids into the NA stalk.
AB  - BACKGROUND: The H5N1 subtype of highly pathogenic avian influenza viruses has
      spread to over 63 countries in Asia, Europe, and Africa and has become endemic in
      poultry. Since 2004, vaccination against H5N1 influenza has become common in
      domestic poultry operations in China. Most influenza vaccines have been produced
      in embryonated chicken eggs. High yield is the essential feature of a good
      vaccine candidate virus. OBJECTIVE: Therefore, the large-scale manufacture of
      such a vaccine requires that the viral yield of H5N1 reassortant vaccine viruses
      in eggs and MDCK cells be increased. METHODS: We generated two sets of
      reassortant H5N1 viruses based on backbone viruses A/Chicken/F/98 (H9N2) and
      A/Puerto Rico/8/34 (H1N1) using reverse genetics. The HAs and NAs of the
      reassortants were derived from the three epidemic H5N1 strains found in China. We
      compared the replication properties of these recombinant H5N1 viruses in
      embryonated chicken eggs and MDCK cells after inserting either 20 or 38 amino
      acids into their NA stalks. RESULTS: In this study, we demonstrated that
      inserting 38 amino acids into the NA stalks can significantly increase the viral
      yield of H5N1 reassortant viruses in both embryonated chicken eggs and MDCK
      cells, while inserting only 20 amino acids into the same NA stalks does not.
      Hemagglutinin inhibition testing and protection assays indicated that recombinant
      H5N1 viruses with 38 aa inserted into their NA stalks had the same antigenicity
      as the viruses with wt-NA. CONCLUSION: These results suggest that the generation
      of an H5N1 recombinant vaccine seed by the insertion of 38 aa into the NA stalk
      may be a suitable and more economical strategy for the increase in viral yield in
      both eggs and MDCK cells for the purposes of vaccine production.

PMID- 21864615
TI  - Health beliefs and attitudes associated with HPV vaccine intention among young
      gay and bisexual men in the Southeastern United States.
AB  - Gay and bisexual men are at increased risk of anal cancer as a result of human
      papillomavirus (HPV) infection. Prophylactic vaccination is a potentially
      effective strategy for preventing anal cancer in this population. The purpose of
      this study was to identify factors associated with gay and bisexual men's
      intention to receive HPV vaccine. In the fall of 2010, 179 self-identified gay
      and bisexual men (mean age 22 years) completed an Internet-based questionnaire
      assessing beliefs and attitudes toward HPV vaccination. Men were recruited from
      college-based and Internet venues throughout the southeastern United States. The
      probability of intent to receive HPV vaccine was modeled using logistic
      regression. A majority of men (93%) had heard of HPV prior to participation but
      were generally unaware of the association of HPV with anal, penile, and oral
      cancers. Only 26% were aware of an HPV vaccine for males. Of the 179
      participants, 64 (36%) were likely to be vaccinated. Men most likely to receive
      HPV vaccine perceived stronger physical and psychological benefits from
      vaccination and had more positive attitudes toward the vaccine. Conversely,
      intent to be vaccinated was negatively associated with concern over the financial
      cost of vaccination. Findings from this study can inform college-based health
      education programs aimed at increasing vaccine uptake among gay and bisexual men.

PMID- 21864616
TI  - Bovine respiratory syncytial virus ISCOMs-Immunity, protection and safety in
      young conventional calves.
AB  - Bovine respiratory syncytial virus (BRSV) is a major cause of bronchiolitis and
      pneumonia in cattle and causes yearly outbreaks with high morbidity in Europe.
      Commercial vaccines against this virus needs improvement of efficacy, especially
      in calves with BRSV-specific maternally derived antibodies (MDA). We previously
      reported that an experimental BRSV-ISCOM vaccine, but not a commercial vaccine,
      induced strong clinical and virological protection in calves with MDA, immunized
      at 7-15 weeks of age. The aim of the present study was to characterize the immune
      responses, as well as to investigate the efficacy and safety in younger animals,
      representing the target population for vaccination. Four groups of five 3-8 week
      old calves with variable levels of BRSV-specific MDA were immunized s.c. twice at
      a 3 weeks interval with (i) BRSV immunostimulating complexes (BRSV-ISCOMs), (ii)
      BRSV-protein, (iii) adjuvant, or (iv) PBS. All calves were challenged with
      virulent BRSV by aerosol 2 weeks later and euthanized on day 6 after infection.
      The cellular and humoral responses were monitored as well as the clinical signs,
      the viral excretion and the pathology following challenge. Despite presence of
      MDA at the time of the immunization, only a minimum of clinical signs were
      observed in the BRSV-ISCOM group after challenge. In contrast, in all control
      groups, clinical signs of disease were observed in most of the animals
      (respiratory rates up to 76min(-1) and rectal temperatures up to 41 degrees C).
      The clinical protection was associated to a highly significant reduction of virus
      replication in the upper and lower respiratory tract of calves, rapid systemic
      and local antibody responses and T helper cell responses dominated by IFNgamma
      production. Animals that did not shed virus detectable by PCR or cell culture
      following challenge possessed particularly high levels of pulmonary IgA. The
      protective immunological responses to BRSV proteins and the ability to overcome
      the inhibiting effect of MDA were dependent on ISCOM borne antigen presentation.

PMID- 21864617
TI  - The potential cost-effectiveness of infant pneumococcal vaccines in Australia.
AB  - Over the last decade infant pneumococcal vaccination has been adopted as part of
      routine immunisation schedules in many developed countries. Although highly
      successful in many settings such as Australia and the United States, rapid
      serotype replacement has occurred in some European countries. Recently two
      pneumococcal conjugate vaccines (PCVs) with extended serotype coverage have been
      licensed for use, a 10-valent (PHiD-CV) and a 13-valent (PCV-13) vaccine, and
      offer potential replacements for the existing vaccine (PCV-7) in Australia. To
      evaluate the cost-effectiveness of PCV programs we developed a static,
      deterministic state-transition model. The perspective for costs included those to
      the government and healthcare system. When compared to current practice (PCV-7)
      both vaccines offered potential benefits, with those estimated for PHiD-CV due
      primarily to prevention of otitis media and PCV-13 due to a further reduction in
      invasive disease in Australia. At equivalent total cost to vaccinate an infant,
      compared to no PCV the base-case cost per QALY saved were estimated at A$64,900
      (current practice, PCV-7; 3+0), A$50,200 (PHiD-CV; 3+1) and A$55,300 (PCV-13;
      3+0), respectively. However, assumptions regarding herd protection, serotype
      protection, otitis media efficacy, and vaccination cost changed the relative cost
      effectiveness of alternative PCV programs. The high proportion of current
      invasive disease caused by serotype 19A (as included in PCV-13) may be a decisive
      factor in determining vaccine policy in Australia.

PMID- 21864618
TI  - Induction and comparison of SIV immunity in Ad5 naive and Ad5 immune non-human
      primates using an Ad5 [E1-, E2b-] based vaccine.
AB  - The effectiveness of recombinant Adenovirus serotype 5 (Ad5) vectors to induce
      immune responses against targeted antigens has been limited by the presence of
      pre-existing or Ad5 vaccine induced anti-vector immunity. The Ad5 [E1-, E2b-]
      platform, a recombinant Ad5 with additional deletions, has been previously
      reported by us to induce immune responses in the presence of Ad5 immunity. In an
      Ad5 immune non-human primate (NHP) model, an Ad5 [E1-, E2b-] construct expressing
      HIV-1 Gag induced immune responses in the presence of pre-existing Ad5 immunity.
      In the present study we expand on these prior observations by comparing the cell
      mediated immune (CMI) responses induced by Ad5 [E1-, E2b-]-SIV-gag/nef in Ad5
      naive and Ad5 immune NHP. Additionally, NHP were immunized with an Ad5 [E1-, E2b
      ]-HIV-pol construct following two homologous administrations of Ad5 [E1-, E2b-]
      SIV-gag/nef to determine if an immune response could be induced against a third
      antigen in the presence of vaccine induced Ad5 immunity. Positive CMI responses,
      as assessed by interferon-gamma (IFN-gamma) secreting lymphocytes, were induced
      against all three antigens. These CMI responses increased over a course of
      multiple immunizations and the response profiles observed in Ad5 naive and Ad5
      immune NHP were similar. No influence of the major histocompatibility complex on
      CMI responses was observed. These data indicate that the new Ad5 [E1-, E2b-]
      platform based vaccine could be used for homologous vaccination regimes to induce
      robust CMI responses in the presence of Ad5 vector immunity.

PMID- 21864620
TI  - Researching routine immunization-do we know what we don't know?
AB  - BACKGROUND: The Expanded Programme on Immunization (EPI), launched in 1974, has
      developed and implemented a range of strategies and practices over the last three
      decades to ensure that children and adults receive the vaccines they need to help
      protect them against vaccine-preventable diseases. Many of these strategies have
      been implemented, resulting in immunization coverage exceeding 80% among children
      one year of age in many countries. Yet millions of infants remain under-immunized
      or unimmunized, particularly in poorer countries. In November 2009, a panel of
      external experts met at the United States Centers for Disease Control and
      Prevention (CDC) to review and identify areas of research required to strengthen
      routine service delivery in developing countries. METHODS: Research opportunities
      were identified utilizing presentations emphasizing existing research, gaps in
      knowledge and key questions. Panel members prioritized the topics, as did other
      meeting participants. FINDINGS: Several hundred research topics covering a wide
      range were identified by the panel members and participants. However there were
      relatively few topics for which there was a consensus that immediate investment
      in research is warranted. The panel identified 28 topics as priorities. 18 topics
      were identified as priorities by at least 50% of non-panel participants; of
      these, five were also identified as priorities by the panel. Research needs
      included identifying the best ways to increase coverage with existing vaccines
      and introduce new vaccines, integrate other services with immunizations, and
      finance immunization programmes. INTERPRETATION: There is an enormous range of
      research that could be undertaken to support routine immunization. However,
      implementation of strategic plans, rather than additional research will have the
      greatest impact on raising immunization coverage and preventing disease,
      disability, and death from vaccine-preventable diseases. The panel emphasized the
      importance of tying operational research to programmatic needs, with a focus on
      efforts to scale up proven best practices in each country, facilitating the full
      implementation of immunization strategies.

PMID- 21864619
TI  - Improving reverse vaccinology with a machine learning approach.
AB  - Reverse vaccinology aims to accelerate subunit vaccine design by rapidly
      predicting which proteins in a pathogenic bacterial proteome are putative
      protective antigens. Support vector machine classification is a machine learning
      approach that has been applied to solve numerous classification problems in
      biological sciences but has not previously been incorporated into a reverse
      vaccinology approach. A training data set of 136 bacterial protective antigens
      paired with 136 non-antigens was constructed and bioinformatic tools were used to
      annotate this data for predicted protein features, many of which are associated
      with antigenicity (i.e. extracellular localization, signal peptides and B-cell
      epitopes). Annotation was used to train support vector machine classifiers that
      exhibited a maximum accuracy of 92% for discriminating protective antigens from
      non-antigens as assessed by a leave-tenth-out cross-validation approach. These
      accuracies were superior to those achieved when annotating training data with
      auto and cross covariance transformations of z-descriptors for hydrophobicity,
      molecular size and polarity, or when classification was performed using
      regression methods. To further validate support vector machine classifiers, they
      were used to rank all the proteins in six bacterial proteomes for their
      antigenicity. Protective antigens from the training data were significantly
      recalled (enriched) in the top 75 ranked proteins for all six proteomes as
      assessed by a Fisher's exact test (p<0.05). This paper describes a superior
      workflow for performing reverse vaccinology studies and provides a benchmark
      training data set that can be used to evaluate future methodological
      improvements.

PMID- 21864621
TI  - Reactogenicity of two 2010 trivalent inactivated influenza vaccine formulations
      in adults.
AB  - OBJECTIVE: To assess the reactogenicity of two 2010 trivalent inactivated
      influenza vaccine (TIV) formulations among adults, including the formulation
      associated with febrile convulsions among children in Australia. DESIGN, SETTING
      AND PARTICIPANTS: We retrospectively interviewed persons aged >=18 years who
      received TIV between 11 March and 24 April 2010 at a large general practice in
      Perth. All 160 persons who received Influvac(r) (Solvay) and a random sample of
      190 of 451 persons who received Fluvax(r) (CSL Biotherapies) were included in the
      assessment; 127 (79%) recipients of Influvac(r) and 156 (82%) of the Fluvax(r)
      recipients completed the interview. MAIN OUTCOME MEASURES: Patient demographics,
      the presence of underlying medical conditions, prior influenza vaccination
      history, self-reported onset of local and/or systemic symptoms within 72 h
      following receipt of 2010 TIV, and use of anti-fever/pain medication following
      TIV vaccination were examined. RESULTS: The mean age of the vaccinees was 54
      years for both the Fluvax(r) and Influvac(r) brand cohorts and there was no
      significant difference between the cohorts with regard to gender or the presence
      of underlying medical conditions. In bivariate analyses, reported swelling (18%
      vs 7%, p=0.009), muscle pain (12% vs 3%, p=0.014) and use of anti-fever/pain
      medication after TIV vaccination (12% vs 2%, p=0.008) were each significantly
      more common for patients who received Fluvax(r) compared to those who received
      Influvac(r). In multivariate analyses simultaneously controlling for age, gender,
      receipt of seasonal influenza vaccine prior to 2010 and receipt of 2009 H1N1
      pandemic vaccine, vaccination with Fluvax(r) TIV was a significant independent
      predictor of muscle pain and/or swelling (OR=3.3, 95% CI 1.5-7.4 p=0.004). No
      significant differences in the proportion of patients reporting systemic
      reactions were observed. CONCLUSIONS: In this setting, 2010 Fluvax(r) was
      associated with a greater likelihood of local reactions among adults, compared to
      2010 Influvac(r) TIV.

PMID- 21864622
TI  - Evaluation of age-related differences in the immunogenicity of a G9 H9N2
      influenza vaccine.
AB  - Avian influenza A/H9N2 viruses can infect people and are viruses considered to be
      a potential pandemic threat. Prior studies with an inactivated G1 clade H9N2
      vaccine reported that persons born before 1968 were more likely to have an immune
      response than younger subjects. We performed a randomized, double-blind trial to
      evaluate whether immune responses following immunization with an inactivated,
      unadjuvanted influenza G9 H9N2 vaccine prepared from A/chicken/Hong Kong/G9/97
      virus were more frequent in persons born in 1964 or earlier (44-59 years) than in
      those born in 1970 or later (18-38 years). One hundred twenty one persons were
      randomized to receive two doses of either 7.5- or 30-mcg of hemagglutinin
      intramuscularly. Post-vaccination serum antibody responses as measured by
      hemagglutination inhibition and microneutralization were either similar in the
      two age cohorts or greater in the younger age group. Persons born before 1968
      were not more likely to respond to a G9 H9N2 influenza vaccine than persons born
      in 1970 or later.

PMID- 21864623
TI  - The innate immune response to Streptococcus pneumoniae in the lung depends on
      serotype and host response.
AB  - Bacteremic pneumonia with some pneumococcal capsular serotypes, including
      serotype 3 (ST3), has been associated with a higher risk of death, whereas
      others, such as ST8, are associated with a lower risk. To provide a molecular
      basis for understanding such differences, we used oligo cDNA microarrays to
      analyze and compare the gene expression profiles of the lungs of Balb/c mice
      infected intranasally with either ST3, strain A66.1, or ST8, strain ATCC 6308
      (6308). Compared to uninfected controls, infection with either A66.1 or 6308 led
      to inoculum-dependent expression of IFN-gamma inducible CXC chemokines among
      other pro-inflammatory genes. To investigate the role that IFN-gamma inducible
      chemokines CXCL9, CXCL10 and CXCL11 play in A66.1- and 6308-induced pneumonia, we
      examined the effect of the absence of their common receptor, CXCR3, on intranasal
      infection in CXCR3(-/-) (Balb/c) mice. Compared to wild type (WT) mice, virulence
      of A66.1 but not 6308 was attenuated in CXCR3(-/-) mice. A66.1-infected CXCR3(-/
      ) mice had fewer lung neutrophils and more alveolar macrophages 48 h after
      infection and fewer blood CFU 72 h after infection. Histopathological examination
      of lung sections revealed less inflammation among A66.1-infected CXCR3(-/-) than
      WT mice. The reduced virulence of A66.1 in CXCR3(-/-) mice suggests that
      inhibition of the functional activity of IFN-gamma inducible chemokines modulates
      the host response to A66.1, in turn suggesting a novel approach to improve
      vaccine-mediated protection against ST3 pneumonia.

PMID- 21864624
TI  - Evaluation of a virosomal H5N1 vaccine formulated with Matrix MTM adjuvant in a
      phase I clinical trial.
AB  - The avian influenza H5 virus epizootic continues to cause zoonosis with human
      fatalities, highlighting the continued need for pandemic preparedness against
      this subtype. This study evaluated the tolerability and immunogenicity of a
      Matrix MTM adjuvanted virosomal H5N1 vaccine in a phase I clinical trial. Sixty
      healthy adults were vaccinated intramuscularly with two doses of influenza H5N1
      (NIBRG-14) virosomal vaccine alone (30 MUg haemagglutinin (HA)) or 1.5, 7.5 or 30
      MUg HA formulated with 50 MUg Matrix MTM adjuvant. The antibody response was
      analysed by haemagglutination inhibition (HI), microneutralisation (MN) and
      single radial haemolysis (SRH) assays. The vaccine was well tolerated in all
      groups but injection site pain was more frequently observed in the Matrix MTM
      adjuvanted groups. The vaccine elicited homologous and heterologous H5N1-specific
      antibody responses and the Matrix MTM adjuvanted formulations met all the EU
      regulatory criteria. In conclusion, Matrix MTM adjuvant was well tolerated and
      augmented the antibody response allowing considerable dose sparing down to 1.5
      MUg HA.

PMID- 21864625
TI  - Pharmacists as providers: targeting pneumococcal vaccinations to high risk
      populations.
AB  - BACKGROUND: Older adults and persons with chronic conditions are at increased
      risk for pneumococcal disease. Severe pneumococcal disease represents a
      substantial humanistic and economic burden to society. Although pneumococcal
      vaccination (PPSV) can decrease risk for serious consequences, vaccination rates
      are suboptimal. As more people seek annual influenza vaccinations at community
      pharmacies, pharmacists have the ability to identify at-risk patients and provide
      PPSV. OBJECTIVES: The objective of this study was to evaluate the impact of
      pharmacists educating at-risk patients on the importance of receiving a
      pneumococcal vaccination. METHODS: Using de-identified claims from a large,
      national pharmacy chain, all patients who had received an influenza vaccination
      between August 1, 2010 and November 14, 2010 and who were eligible for PPSV were
      identified for the analysis. Based on the Advisory Committee on Immunization
      Practices recommendations, at-risk patients were identified as over 65 years of
      age or as aged 2-64 with a comorbid conditions. A benchmark medical and pharmacy
      claims database of commercial and Medicare health plan members was used to derive
      a PPSV vaccination rate typical of traditional care delivery to compare to
      pharmacy-based vaccination. Period incidence of PPSV was calculated and compared.
      RESULTS: Among the 1.3 million at-risk patients who were vaccinated by a
      pharmacist during the study period, 65,598 (4.88%) also received a pneumococcal
      vaccine. This vaccination rate was significantly higher than the benchmark rate
      of 2.90% (34,917/1,204,104; p<.001) representing traditional care. Patients aged
      60-70 years had the highest vaccination rate (6.60%; 26,430/400,454) of any age
      group. CONCLUSIONS: Pharmacists were successful at identifying at-risk patients
      and providing additional immunization services. Concurrent immunization of PPSV
      with influenza vaccination by pharmacists has potential to improve PPSV coverage.
      These results support the expanding role of community pharmacists in the
      provision of wellness and prevention services.

PMID- 21864627
TI  - Preparing for introduction of a dengue vaccine: recommendations from the 1st
      Dengue v2V Asia-Pacific Meeting.
AB  - Infection with dengue virus is a major public health problem in the Asia-Pacific
      region and throughout tropical and sub-tropical regions of the world. Vaccination
      represents a major opportunity to control dengue and several candidate vaccines
      are in development. Experts in dengue and in vaccine introduction gathered for a
      two day meeting during which they examined the challenges inherent to the
      introduction of a dengue vaccine into the national immunisation programmes of
      countries of the Asia-Pacific. The aim was to develop a series of recommendations
      to reduce the delay between vaccine licensure and vaccine introduction. Major
      recommendations arising from the meeting included: ascertaining and publicising
      the full burden and cost of dengue; changing the perception of dengue in non
      endemic countries to help generate global support for dengue vaccination;
      ensuring high quality active surveillance systems and diagnostics; and
      identifying sustainable sources of funding, both to support vaccine introduction
      and to maintain the vaccination programme. The attendees at the meeting were in
      agreement that with the introduction of an effective vaccine, dengue is a disease
      that could be controlled, and that in order to ensure a vaccine is introduced as
      rapidly as possible, there is a need to start preparing now.

PMID- 21864626
TI  - Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted
      with HIV-1 recombinant MVA among healthy adults in Tanzania.
AB  - BACKGROUND: We conducted a phase I/II randomized placebo-controlled trial with
      the aim of exploring whether priming with a low intradermal dose of a multiclade,
      multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine
      given intramuscularly prior to boosting with a heterologous HIV-1 MVA among
      healthy adults in Dar es Salaam, Tanzania. METHODS: Sixty HIV-uninfected
      volunteers were randomized to receive DNA plasmid vaccine 1mg intradermally (id),
      n=20, or 3.8mg intramuscularly (im), n=20, or placebo, n=20, using a needle-free
      injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B;
      p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA
      (10(8)pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered
      im at month 9 and 21. RESULTS: The vaccines were well tolerated. Two weeks after
      the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-gamma ELISpot
      responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees
      responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA
      boost, 28/29 (97%) vaccinees had IFN-gamma ELISpot responses, 27 (93%) to Gag and
      23 (79%) to Env. The id-primed recipients had significantly higher responses to
      Env than im recipients. Intracellular cytokine staining for Gag-specific IFN
      gamma/IL-2 production showed both CD8(+) and CD4(+) T cell responses. All
      vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted
      in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160
      after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were
      negative for neutralizing antibodies against clade B, C and CRF01_AE
      pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response
      rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE
      virus tested. CONCLUSIONS: This vaccine approach is safe and highly immunogenic.
      Low dose, id HIV-DNA priming elicited higher and broader cell-mediated immune
      responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose
      given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts
      efficiently induced Env-antibody responses.

PMID- 21864628
TI  - Perspective of the U.S. Food and Drug Administration on concomitant
      administration of Zostavax and Pneumovax.

PMID- 21864629
TI  - Airborne asbestos exposures associated with work on asbestos fire sleeve
      materials.
AB  - Asbestos-containing fire sleeves have been used as a fire protection measure for
      aircraft fluid hoses. This investigation was conducted to determine the level of
      airborne asbestos fiber exposure experienced by mechanics who work with fire
      sleeve protected hoses. Duplicate testing was performed inside a small, enclosed
      workroom during the fabrication of hose assemblies. Personal air samples taken
      during this work showed detectable, but low airborne asbestos fiber exposures.
      Analysis of personal samples (n=9) using phrase contract microscopy (PCM)
      indicated task duration airborne fiber concentrations ranging from 0.017 to 0.063
      fibers per milliliter (f/ml) for sampling durations of 167-198 min, and 0.022
      0.14 f/ml for 30 min samples. Airborne chrysotile fibers were detected for four
      of these nine personal samples, and the resulting asbestos adjusted airborne
      fiber concentrations ranged from 0.014 to 0.025 f/ml. These results indicate that
      work with asbestos fire sleeve and fire sleeve protected hose assemblies, does
      not produce regulatory noncompliant levels of asbestos exposure for persons who
      handle, cut and fit these asbestos-containing materials.

PMID- 21864630
TI  - The relationship between serotonin transporter gene promoter polymorphism and
      serum lipid levels at young age in a longitudinal population-representative
      study.
AB  - The serotonin transporter gene promoter region polymorphism (5-HTTLPR) has been
      linked to psychiatric disorders, mostly anxiety and affective disorders. In
      elderly populations 5-HTTLPR polymorphism has also been reported to be associated
      with serum lipid levels. We have examined the interaction of the 5-HTTLPR
      polymorphism and the markers of lipid metabolism at young age in a longitudinal,
      population-representative cohort study. The sample of the Estonian Children
      Personality Behaviour and Health Study (initially cohorts of 9 and 15 year old
      children, complete lipid and genotype data for n=1176) was examined throughout 10
      years. Subjects were genotyped and the levels of low-density lipoproteins, high
      density lipoproteins, triglycerides, and total cholesterol were measured.
      Children and adolescents carrying the s allele of the 5-HTTLPR polymorphism had
      lower levels of low-density lipoprotein and total cholesterol. At the age of 25,
      the s allele carriers had higher levels of high-density lipoproteins. These
      associations were independent of gender. Thus the 5-HTTLPR can be associated with
      the serum lipid levels and in particular low-density lipoproteins already in a
      young age.

PMID- 21864631
TI  - Anti-inflammatory effects of [6]-shogaol: potential roles of HDAC inhibition and
      HSP70 induction.
AB  - Ginger extracts have been reported to have anti-inflammatory, anti-oxidant, and
      anti-cancer effects. [6]-shogaol is one of the most bioactive components of
      ginger rhizomes. This study assessed the [6]-shogaol's ability to protect
      cultured primary rat astrocytes against lipopolysaccharide (LPS)-induced
      inflammation. [6]-shogaol was shown to suppress the release of pro-inflammatory
      cytokines and decreased the level of inducible nitric oxide syntheses (iNOS),
      cyclooxygenase-2 (COX-2), and phospho-NF-kB in LPS-treated astrocytes.
      Furthermore, [6]-shogaol treatment markedly up-regulated histone H3 acetylation
      and suppressed histone deacetylase (HDAC)1 expression. In addition, [6]-shogaol
      treatment also increased the expression of heat-shock protein (HSP)70. The
      neuroprotective, neurotrphic, and anti-inflammatory properties of [6]-shogaol may
      be translated to improvements in neurological performance. [6]-Shogaol's ability
      to inhibit HDAC was comparable to that of commonly used HDAC inhibitors
      Trichostatin A and MS275. Taken together, our results suggest that [6]-shogaol
      can significantly attenuate a variety of neuroinflammatory responses by inducing
      HSP70, that is associated with HDAC inhibition in cortical astrocytes.

PMID- 21864632
TI  - Northeast Portuguese propolis protects against staurosporine and hydrogen
      peroxide-induced neurotoxicity in primary cortical neurons.
AB  - The present work describes the protective effects of the crude Northeast
      Portuguese propolis enriched phenolic extract against staurosporine (STS) and
      hydrogen peroxide (H(2)O(2))-induced neurotoxicity. These two stress inducers act
      through various pathways, including the production of reactive oxygen species
      (ROS) and the induction of apoptosis through caspases activation. STS (25 and 50
      nM) and H(2)O(2) (100 MUM) increased intracellular ROS and diminished cellular
      reducing ability in cultured cortical neurons, under conditions unrelated with
      massive loss of plasma membrane integrity, suggesting decreased neuronal
      function. Moreover, 25 nM STS and 100 MUM H(2)O(2) increased caspase-3 activity
      by about 2.8- and 4.6-fold, respectively. Pre-treatment of cortical neurons with
      the ethanolic extract of propolis (EEP) in the range of 0.01-1 MUg/ml showed no
      protective effect on cell reducing capacity, but decreased H(2)O(2)-stimulated
      increment in ROS production by about 17%. In addition, the EEP attenuated STS- or
      H(2)O(2)-induced activation of caspase-3 by 23-39%. Overall, the results show
      moderate protective effects induced by Northeast Portuguese EEP in cortical
      neurons subjected to stress stimuli.

PMID- 21864633
TI  - Determination and study on dissipation of 1-naphthylacetic acid in garlic and
      soil using high performance liquid chromatography-tandem mass spectrometry.
AB  - A simple, quick and reliable analytical method for the determination of 1
      naphthylacetic acid in garlic and soil has been developed in this study. The
      residual levels and dissipation rates of 1-naphthylacetic acid in garlic and soil
      were determined by high performance liquid chromatography-tandem mass
      spectroscopy (HPLC-MS/MS). The limit of quantification (LOQ) of the developed
      method was 0.005 mg/kg. The half-lives of 1-naphthylacetic acid in garlic plants
      and soil were 0.80-1.4 days and 0.94-2.0 days, respectively. The final residues
      of 1-naphthylacetic acid in garlic, garlic sprout and soil could not be detected
      and were all below 0.05 mg/kg (the MRL of EU). Results of the ultimate residues
      in garlic and soil showed that this pesticide is safe to be used under the
      recommended dosages.

PMID- 21864634
TI  - Infants exposure to aflatoxin M1 as a novel foodborne zoonosis.
AB  - Occurrence of aflatoxin M(1) (AFM(1)) in infant formula milk powder (IFMP) and
      maternal breast milk (MBM) was investigated as a risk factor affects the health
      of newborns in Egypt. A total of 125 IFMP and 125 MBM samples were collected and
      examined for the presence of AFM(1) using competitive ELISA test. The results
      indicated that the relative risk (RR) of exposure to AFM(1) via consumption of
      MBM was higher than IFMP (RR; 1.6, 95%CI; 1.28-2.03, p=0.0001). The mean
      concentrations of AFM(1) were significantly differed (p<0.0001) between MBM
      (74.413 +/- 7.070 ng/l) and IFMP (9.796 +/- 1.036 ng/l). High frequency
      distributions were detected within the range of 5-25 ng/l and >50-100 ng/l in
      IFMP and MBM, respectively. The average daily exposure of newborns to AFM(1) via
      consumption of MBM and IFMP was 52.684 and 8.170 ng, respectively, with a
      significant difference at p<0.0001. Consumption of raw milk by lactating mothers
      exhibited a significant correlation (p<0.0001) with the presence of AFM(1) in
      their milk. In conclusion, this work established a pioneering concept that AFM(1)
      may be considered as an etiological factor for a novel foodborne zoonosis
      identified as Aflatoxicosis M(1).

PMID- 21864635
TI  - The synergistic effect of sodium chlorite and bromochloroacetic acid on BrO3(-)
      induced renal cell death.
AB  - Bromate (BrO(3)(-)) is a drinking water disinfection by-product (DBP) that
      induces renal cell death via DNA damage-dependent and -independent mechanisms.
      Drinking water contains other DBPs in addition to BrO(3)(-). We tested the effect
      of two of these, sodium chlorite (NaClO(2)) and bromochloroacetic acid (BCAA), on
      BrO(3)(-) cytotoxicity in normal rat kidney (NRK) cells. NaClO(2) and BCAA alone
      induced cytotoxicity at concentrations of over 20ppm, while BrO(3)(-) was only
      moderately cytotoxic at concentrations of 200ppm. Combining BrO(3)(-) with
      NaClO(2) or BCAA alone enhanced cytotoxicity 1.5-4 fold. Exposing cells to all
      three compounds induced synergistic-like increases in cytotoxicity. This effect
      did not correlate to increases in reactive oxygen species (ROS), even though all
      three compounds induced ROS formation alone. NaClO(2), but not BCAA, increased
      BrO(3)(-)-mediated DNA damage as measured by 8-hydroxydeoxyguanosine (8-OHdG)
      staining. In addition, NaClO(2), but not BCAA, decreased BrO(3)(-)-induced G2/M
      cell cycle arrest. Both compounds increased apoptosis in the presence of BrO(3)(
      ) as assessed by annexin V, PI, and DAPI staining. This is in contrast to BrO(3)(
      ) treatment alone, which induced necrosis. Immunoblot analysis showed that both
      NaClO(2) and BCAA increased p38 activation; however, consistent with 8-OHdG
      staining, only NaClO(2) increased BrO(3)(-)-induced histone H2AX phosphorylation,
      a marker of DNA damage. In contrast, BCAA, but not NaClO(2), increased BrO(3)(-)
      induced phosphorylation of p53. These data support the novel finding that
      mixtures of DBPs increase BrO(3)(-)-induced renal cell death by DNA-dependent and
      -independent mechanisms, and could alter how the risk of these DBPs towards
      humans is assessed.

PMID- 21864636
TI  - Medium-term multi-organ carcinogenesis bioassay of ethyl tertiary-butyl ether in
      rats.
AB  - The modifying potential of ethyl tertiary-butyl ether (ETBE) on tumor development
      was investigated in a medium-term multi-organ carcinogenesis bioassay using male
      F344 rats. Animals were sequentially given 5 carcinogens with different target
      sites in the first 4 weeks for multi-organ initiation. After one week they
      received ETBE by gavage at dose levels of 0 (control), 300 or 1000mg/kg/day until
      experimental week 28. Further groups were also given ETBE at doses of 0 or
      1000mg/kg/day without prior carcinogen application. Incidences and multiplicities
      of follicular cell hyperplasias and neoplasms in the thyroid were significantly
      increased at dose levels of more than 300mg/kg/day. Combined incidences of
      squamous cell hyperplasias and papillomas of the forestomach were also
      significantly increased at 300 and 1000mg/kg/day. Incidences and multiplicities
      of adenocarcinomas in the colon were increased at 1000mg/kg/day. The numbers and
      areas of glutathione S-transferase placental form (GST-P) positive foci per unit
      area of the liver sections, and the incidence of hepatocellular adenomas were
      also significantly increased at 1000mg/kg/day, along with multiplicities of
      atypical hyperplasias of renal tubules of the kidney and the incidence of
      papillomatosis of the urinary bladder. This latter lesion was also seen at low
      incidence at 1000mg/kg/day without initiation. Thus, the current results indicate
      that ETBE has tumor promoting potential for the thyroid and forestomach at dose
      levels of 300mg/kg/day and more, and for the colon, liver, kidney and urinary
      bladder at 1000mg/kg/day, under the present experimental conditions.

PMID- 21864637
TI  - Prior or coinstantaneous oral exposure to environmental immunosuppressive agents
      aggravates mite allergen-induced atopic dermatitis-like immunoreaction in NC/Nga
      mice.
AB  - BACKGROUND: Immunosuppressive environmental chemicals may increase the potency of
      allergens and thereby play a role in the development of allergic diseases such as
      allergic rhinitis, asthma and atopic dermatitis (AD). OBJECTIVES: This study's
      primary objective was to examine the mechanisms behind the development of
      allergic diseases and immunosuppression induced by some environmental chemicals.
      We focused on the aggravation of AD by the organophosphorus pesticide O,O-diethyl
      O-4-nitro-phenylthiophosphate (parathion) and the organochlorine pesticide 1,1,1
      trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor), in NC/Nga mice
      sensitized with extract of Dermatophagoides farinae (Df). METHODS: NC/Nga mice
      were exposed orally to parathion or methoxychlor prior or coinstantaneous with
      sensitization with Df. The mice were subsequently challenged with Df. One day
      after the last challenge with Df, we analyzed dermatitis severity and expression
      of genes in the ear auricle, immunoglobulin (Ig) E and IgG(2a) levels in serum,
      and in auricular lymph nodes, T- or B-cell numbers and cytokine production.
      RESULTS: Prior exposure to parathion or methoxychlor induced marked increases in
      the following: dermatitis severity and gene expression in the ear auricle, IgE
      and IgG(2a) levels in serum, expression of surface antigens on helper T-cell and
      IgE-positive B-cell, production of Th1 and Th2 cytokines, and production of IgE
      in auricular lymph-node cells. In contrast, coinstantaneous exposure to parathion
      or methoxychlor yielded, at most, small but significant decreases in all
      parameters. CONCLUSIONS: Our results indicate that atopic dermatitis can be
      aggravated by prior exposure to immunosuppressive environmental chemicals.

PMID- 21864638
TI  - Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent,
      CP-31398, in rats and dogs.
AB  - CP-31398 (N'-[2-[2-(4-methoxyphenyl)ethenyl]-4-quinazolinyl]-N,N-dimethyl-1,3
      propanediamine dihydrochloride) is a styrylquinazoline that stabilizes the DNA
      binding conformation of p53, thereby maintaining the activity of p53 as a
      transcription factor and tumor suppressor. In consideration of the potential use
      of p53 stabilizers for cancer prevention and therapy, 28-day studies (with
      recovery) were performed to characterize the toxicity of CP-31398 in rats and
      dogs. In the rat study, groups of 15 CD rats/sex received daily gavage exposure
      to CP-31398 at 0, 40, 80, or 160mg/kg/day (0, 240, 480, or 960mg/m(2)/day). In
      the dog study, groups of five beagle dogs received daily gavage exposure to CP
      31398 at 0, 10, 20, or 40mg/kg/day (0, 200, 400, or 800mg/m(2)/day). The high
      dose of CP-31398 induced mortality in both species: seven male rats and four
      female rats died as a result of hepatic infarcts, and two female dogs died as a
      result of hepatic necrosis without evidence of thrombosis. No deaths were seen in
      the mid- or low-dose groups in either species. In dogs, sporadic emesis was seen
      in the high dose and mid dose groups, and reductions in body weight gain were
      observed in all drug-exposed groups. CP-31398 induced mild anemia in both
      species; clinical pathology data also demonstrated hepatic toxicity, renal
      toxicity, inflammatory reactions, and coagulopathies in rats in the high dose and
      mid dose groups. Treatment-related microscopic changes in high dose and mid dose
      rats were identified in the liver, kidney, heart, bone marrow, lung, adrenals,
      spleen, thymus, skeletal muscle, and ovary; microscopic changes in the liver,
      heart, lung, and adrenals persisted through the recovery period. In dogs,
      microscopic changes were identified in the central nervous system, lung, and
      liver; changes in all tissues remained at the end of the recovery period. The
      liver is the primary site of limiting toxicity for CP-31398 in rats, and is also
      a key site of toxicity in dogs. The maximum tolerated dose (MTD) for subchronic
      oral administration of CP-31398 is 80mg/kg/day (480mg/m(2)/day) in rats and
      20mg/kg/day (400mg/m(2)/day) in dogs. Although only modest and apparently
      reversible toxicities (microscopic changes in rats; reductions in body weight
      gain and alterations in red cell parameters in dogs) were seen in the low dose
      groups, no observed adverse effect levels (NOAELs) for CP-31398 could not be
      established for either species. The toxicity of CP-31398 suggests that this agent
      may not be suitable for use in cancer prevention. However, should in vivo
      antitumor efficacy be achievable at doses that do not induce limiting toxicity,
      CP-31398 may have utility as a cancer therapeutic. Modification of the primary
      sites of CP-31398 metabolism (N-demethylation of the alkyl side chain;
      hydroxylation and O-demethylation of the styryl benzene group) may result in the
      development of CP-31398 analogs with comparable pharmacologic activity and
      reduced toxicity.

PMID- 21864639
TI  - Hepato-protective effects of loganin, iridoid glycoside from Corni Fructus,
      against hyperglycemia-activated signaling pathway in liver of type 2 diabetic
      db/db mice.
AB  - Accumulating evidence indicates that uncontrolled diabetes leads to the
      progression of diabetic complications such as liver disorder. The present study
      was carried out to elucidate the protective role of loganin extracted from Corni
      Fructus against hepatic oxidative stress caused by type 2 diabetes. Loganin (20
      or 100mg/kg body weight/day, p.o.) was administered every day for 8 weeks to
      db/db mice, and its effect was assessed on comparison with vehicle-treated db/db
      and m/m mice. The administration of loganin led to a decrease in glucose and
      elevation of leptin in serum. The diabetic oxidative stress was attenuated by
      loganin through inhibitions of reactive oxygen species production and lipid
      peroxidation in the serum and liver. The expression of proteins induced by
      oxidative stress was significantly up-regulated in the liver of diabetic db/db
      mice; however, the expressions of both Nox-4 and p22(phox) were decreased
      significantly by loganin administration. Loganin showed a crucial effect in the
      inflammation-activated signaling pathway through the regulation of NF-kappaB, COX
      2, and iNOS. It was also found to regulate the anti-inflammatory factors Nrf-2
      and HO-1 in hepatic tissue. Moreover, expression of MCP-1 was significantly down
      regulated in the loganin-treated db/db mice. Furthermore, loganin administration
      showed a protective effect against apoptosis by the regulation of Bcl-2 and
      cytochrome c. The present study demonstrated that the administration of loganin
      isolated from Corni Fructus had a protective effect against hepatic oxidative
      stress under type 2 diabetes through regulations of protein expressions related
      to oxidative stress, inflammation, and apoptosis.

PMID- 21864640
TI  - Comparison of various iron chelators used in clinical practice as protecting
      agents against catecholamine-induced oxidative injury and cardiotoxicity.
AB  - Catecholamines are stress hormones and sympathetic neurotransmitters essential
      for control of cardiac function and metabolism. However, pathologically increased
      catecholamine levels may be cardiotoxic by mechanism that includes iron-catalyzed
      formation of reactive oxygen species. In this study, five iron chelators used in
      clinical practice were examined for their potential to protect cardiomyoblast
      derived cell line H9c2 from the oxidative stress and toxicity induced by
      catecholamines epinephrine and isoprenaline and their oxidation products.
      Hydroxamate iron chelator desferrioxamine (DFO) significantly reduced oxidation
      of catecholamines to more toxic products and abolished redox activity of the
      catecholamine-iron complex at pH 7.4. However, due to its hydrophilicity and
      large molecule, DFO was able to protects cells only at very high and clinically
      unachievable concentrations. Two newer chelators, deferiprone (L1) and
      deferasirox (ICL670A), showed much better protective potential and were effective
      at one or two orders of magnitude lower concentrations as compared to DFO that
      were within their clinically relevant plasma levels. Ethylenediaminetetraacetic
      acid (EDTA), dexrazoxane (ICRF-187, clinically approved cardioprotective agent
      against anthracycline-induced cardiotoxicity) as well as selected beta
      adrenoreceptor antagonists and calcium channel blockers exerted no effect. Hence,
      results of the present study indicate that small, lipophilic and iron-specific
      chelators L1 and ICL670A can provide significant protection against the oxidative
      stress and cardiomyocyte damage exerted by catecholamines and/or their reactive
      oxidation intermediates. This potential new application of the clinically
      approved drugs L1 and ICL670A warrants further investigation, preferably using
      more complex in vivo animal models.

PMID- 21864641
TI  - Dentine remineralization induced by two bioactive glasses developed for air
      abrasion purposes.
AB  - OBJECTIVES: The present study aimed to evaluate dentine remineralization through
      a 7-day period of artificial saliva (AS) storage induced by bioactive glass 45S5
      (BAG) and by bioactive glass modified with soda-lime spherical glass. METHODS:
      Partially demineralized dentine disks were treated by BAG or the spherical-glass
      modified bioactive glass (M-BAG) and subsequently immersed in AS for 7 days.
      Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR)
      was used to quantitatively analyse the mineral variation of the dentine surface
      by calculating the spectra parameters. X-ray diffraction (XRD) and energy
      dispersive X-ray analysis (EDX) were performed on completely demineralized
      dentine to confirm the apatite formation. The roughness of the dentine surface
      was evaluated by atomic force microscopy (AFM) and the morphology was also
      examined by scanning electron microscopy (SEM). RESULTS: ATR-FTIR showed a
      significant increase of the mineral matrix area ratio in dentine specimens
      treated with the two bioactive glasses subsequent to 7 days of AS storage. The
      XRD spectrum exhibited apatite growth and mineral elements could be found on
      completely demineralized samples analysed by EDX after remineralization
      treatments. The dentine specimens treated with bioactive glass showed lower
      roughness, and most of the dentinal tubules appeared completely occluded during
      the AFM and SEM examination. CONCLUSIONS: Although the concentration of bioactive
      glass in the M-BAG is 60% of that contained in the original version, both
      formulations have similar potential in dentine remineralization. These bioactive
      powders developed for air-abrasive use may be considered as innovative bioactive
      materials for therapeutic remineralization of dental hard tissues.

PMID- 21864642
TI  - Separate contribution of enamel and dentine to overall tooth colour change in
      tooth bleaching.
AB  - OBJECTIVES: The aim of this study was to evaluate the separate contribution of
      enamel (E) and dentine (D) to the colour change of tooth which subjected to 10%
      carbamide peroxide (CP) gels using a novel recombined enamel-dentine (Recombined
      ED) study model. METHODS: 120 enamel-dentine (ED) samples (four homogeneous
      premolar ED from each patient; total=30*4 ED) were involved in the present study.
      Two homogeneous ED samples were bleached with 10% CP and the other two ones were
      stored in artificial saliva for one, two or four weeks. After treatment, four
      kinds of layers were prepared from each four homogeneous ED samples by removing
      enamel or dentine part: bleached-enamel (BE), bleached-dentine (BD), control
      enamel (CE) and control-dentine (CD). Initial and final colour records of samples
      were taken with a spectrophotometer in CIELab system. The contribution of
      enamel/dentine to the colour change of tooth (CTCC) was calculated by measuring
      the colour difference DeltaE between two different enamel-dentine combinations
      (DeltaE between BE/BD and CE/BD for enamel; DeltaE between BE/BD and BE/CD for
      dentine). Translucency parameter (TP) was obtained by calculating the colour
      difference between enamel on black and white backings. RESULTS: ED and recombined
      ED were significantly correlated in L(*)a(*)b(*) values both for unbleached
      samples and bleached samples. Bleaching resulted in a significant colour change
      (DeltaE) of E, D and ED samples. The TP of BE was significantly lower than that
      of CE. The CTCC of enamel was significantly higher than that of dentine all
      through the time points. CONCLUSIONS: Enamel played a more important role than
      dentine in tooth bleaching due to the changes in translucency and colour.

PMID- 21864643
TI  - Evaluation of the subgingival microbiota of alcoholic and non-alcoholic
      individuals.
AB  - OBJECTIVES: The aim of this study was to evaluate the composition of the
      subgingival microbiota of alcoholic and non-alcoholic individuals. METHODS: The
      study was conducted with 49 alcoholic and 49 non-alcoholic males of the Philippe
      Pinel Institute, Rio de Janeiro, Brazil. The subjects were selected by
      convenience and two criteria were used to diagnose alcohol dependence: the CAGE
      (cut-down, annoyed, guilt, eyes-opener) questionnaire and the International
      Statistical Classification of Diseases, 10th edition (WHO). Subgingival biofilm
      samples were obtained from 4 sites, 2 with probing depth (PD) >= 4 mm and 2 sites
      with PD < 4 mm. The presence and levels of 45 bacterial taxa were analysed using
      the checkerboard technique. RESULTS: The prevalence of bacterial species was not
      significantly different between groups. However, alcoholics showed significantly
      higher mean counts of Aggregactibacter actinomycetemcomitans, Fusobacterium
      nucleatum nucleatum, and Porphyromonas gingivalis (adjusted p < 0.001). Moreover,
      alcoholics harboured significantly higher mean levels of Capnocytophaga
      sputigena, Fusobacterium nucleatum vincentii, F. nuc. nucleatum, Gemella
      morbillorum, Neisseria mucosa, P. gingivalis, Streptococcus gordonii, and
      Tannerella forsythia at sites with PD < 4 mm or >= 4 mm compared to non
      alcoholics (p <= 0.001). Of interest, shallow sites of alcoholics presented
      significantly higher mean levels of F. nuc. vincentii, F. nuc nucleatum, P.
      gingivalis, and T. forsythia than sites with PD >= 4 mm of non-alcoholics (p <=
      0.001). CONCLUSIONS: Alcoholics and non-alcoholics present a diverse and complex
      microbiota; however, alcoholics harbour significantly higher levels of
      periodontopathic species in the subgingival microbiota than non-alcoholics.

PMID- 21864644
TI  - Clinical and antimicrobial evaluation of a mouthwash and toothpaste for
      xerostomia: a randomized, double-blind, crossover study.
AB  - OBJECTIVES: Specific toothpaste and mouthwash for xerostomia based on triclosan,
      fluoride, and mineral salts were studied in order to evaluate their efficacy in
      improving the quality of life as well as their in vitro antimicrobial action.
      MATERIALS AND METHODS: 30 patients with dry mouth and hyposalivation confirmed by
      sialometry were included in a randomized, double-blind, crossover study, during
      two weeks for each experimental phase. Dryness and oral comfort, difficulty in
      speaking, chewing, swallowing and using dental prostheses, as well as taste and
      sleep disorders were evaluated. Values of minimal biocidal and minimal inhibitory
      concentrations of both products against microorganisms that often cause oral
      disorders in these patients were determined and compared. RESULTS: The use of the
      mouthwash and toothpaste studied improved the dry mouth symptoms, whilst no
      significant differences when compared with the salivary enzyme substitutes were
      observed. The test products showed, in general, a higher biocidal and inhibitory
      action than the control products, with particularly noteworthy action against
      cariogenic bacteria. CONCLUSIONS: The use of a toothpaste and mouthwash based on
      triclosan, fluoride, gingival revitalizers and mineral salts, improves the
      quality of life of patients suffering xerostomia.

PMID- 21864645
TI  - Receptor for advanced glycation end products (RAGE)-expressing endothelial cells
      co-express AGE and S100 in human periapical granulomas.
AB  - OBJECTIVE: The engagement of the receptor for advanced glycation end products
      (RAGE) by AGE or S100 perturbs homeostatic mechanisms and provides a basis for
      cellular dysfunction in pathological situations. To assess the mechanism of
      vascular immune reactions in chronic periapical periodontitis, we analysed co
      expression of RAGE and AGE or S100 in periapical granulomas. METHODS: Surgically
      removed periapical lesions, which had been diagnosed as chronic periodontitis,
      were inspected histologically using paraffin-embedded sections stained with
      haematoxylin and eosin. Cryostat sections of the tissues, which were identified
      histologically as periapical granulomas, were then examined by double
      immunohistochemistry using polyclonal antibodies raised against human CD34 and
      monoclonal antibodies specific for human RAGE, AGE or S100. Dual-colour
      immunofluorescence image analysis was also performed to assess the co-expression
      of RAGE and AGE or RAGE and S100 by endothelial cells. RESULTS: Marked expression
      of RAGE, AGE, and S100 by CD34(+) endothelial cells was noted. Dual-colour
      immunofluorescence image analysis revealed that the RAGE-expressing endothelial
      cells co-expressed AGE and S100; however, the number of RAGE-AGE-expressing
      endothelial cells was significantly higher than that of RAGE-S100-expressing
      endothelial cells. CONCLUSIONS: Co-expression of RAGE and AGE by endothelial
      cells in periapical granulomas is more relevant than that of RAGE and S100. The
      possible engagement of RAGE and AGE may trigger cellular activation and mediate
      tissue injury.

PMID- 21864646
TI  - Effects of resveratrol on biomarkers of oxidative stress and on the activity of
      delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin
      induced diabetic rats.
AB  - The present study investigated the effects of resveratrol (RV), a polyphenol with
      potent antioxidant properties, on oxidative stress parameters in liver and
      kidney, as well as on serum biochemical parameters of streptozotocin (STZ)
      induced diabetic rats. Animals were divided into six groups (n = 8):
      control/saline; control/RV 10 mg/kg; control/RV 20 mg/kg; diabetic/saline;
      diabetic/RV10 mg/kg; diabetic/RV 20 mg/kg. After 30 days of treatment with
      resveratrol the animals were sacrificed and the liver, kidney and serum were used
      for experimental determinations. Results showed that TBARS levels were
      significantly increased in the diabetic/saline group and the administration of
      resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups
      (P < 0.05). The activities of catalase (CAT), superoxide dismutase (SOD) and
      aminolevulinic acid dehydratase (delta-ALA-D) and the levels of non protein
      thiols (NPSH) and vitamin C presented a significant decrease in the
      diabetic/saline group when compared with the control/saline group (P < 0.05). The
      treatment with resveratrol was able to prevent these decrease improving the
      antioxidant defense of the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). In
      addition, the elevation in serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and gamma-glutamiltransferase (gamma-GT) activities as
      well as in levels of urea, creatinine, cholesterol and triglycerides observed in
      the diabetic/saline group were reverted to levels close to normal by the
      administration of resveratrol in the diabetic/RV10 and diabetic/RV20 groups (P <
      0.05). These findings suggest that resveratrol could have a protector effect
      against hepatic and renal damage induced by oxidative stress in the diabetic
      state, which was evidenced by the capacity of this polyphenol to modulate the
      antioxidant defense and to decrease the lipid peroxidation in these tissues.

PMID- 21864648
TI  - Direct projection from the visual associative cortex to the caudate nucleus in
      the feline brain.
AB  - Recent morphological and physiological studies support the assumption that the
      extrageniculate ascending tectofugal pathways send visual projection to the
      caudate nucleus (CN) in amniotes. In the present study we investigate the
      anatomical connection between the visual associative cortex along the anterior
      ectosylvian sulcus (AES) and the CN in adult domestic cats. An anterograde tracer
      - fluoro-dextrane-amine - was injected into the AES cortex. The distribution of
      labeled axons was not uniform in the CN. The majority of labeled axons and
      terminal like puncta was found only in a limited area in the dorsal part of the
      CN between the coordinates anterior 12-15. Furthermore, a retrograde tracer -
      choleratoxin-B - was injected into the dorsal part of the CN between anterior 12
      and 13. We detected a large number of labeled neurons in the fundus and the
      dorsal part of the AES between the coordinates anterior 12-14. Based upon our
      recent results we argue that there is a direct monosynaptic connection between
      the visual associative cortex along the AES and the CN. Beside the posterior
      thalamus, the AES cortex should also participate in the transmission of the
      tectal visual information to the CN. This pathway is likely to convey complex
      information containing both sensory and motor components toward the basal
      ganglia, which supports their integrative function in visuomotor actions such as
      motion and novelty detection and saccade generation.

PMID- 21864649
TI  - Lesions of the ventral ascending noradrenergic bundles decrease the stress
      response to occlusal disharmony in rats.
AB  - Occlusal disharmony induced by placing an acryl cap on the lower incisors of rats
      is perceived as chronic stress. This chronic stress activates corticotropin
      releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus
      (PVN), resulting in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis.
      The ventral ascending noradrenergic bundles (V-NAB) from the brainstem innervate
      the PVN. To investigate the relationship between the response of the HPA axis and
      the V-NAB, we examined changes in extracellular noradrenaline (NA) in the PVN and
      plasma corticosterone, the final output of the HPA axis, following occlusal
      disharmony in rats injected with 6-hydroxydopamine (6-OHDA), a specific
      catecholamine neurotoxin. 6-OHDA microinjection into the V-NAB reduced the
      magnitude of the responses of extracellular NA in the PVN and the plasma
      corticosterone to occlusal disharmony. Our results suggest that V-NAB to the PVN
      are involved in occlusal disharmony-induced activation of the HPA axis.

PMID- 21864647
TI  - Sphingosine-1-phosphate rapidly increases cortisol biosynthesis and the
      expression of genes involved in cholesterol uptake and transport in H295R
      adrenocortical cells.
AB  - In the acute phase of adrenocortical steroidogenesis, adrenocorticotrophin (ACTH)
      activates a cAMP/PKA-signaling pathway that promotes the transport of free
      cholesterol to the inner mitochondrial membrane. We have previously shown that
      ACTH rapidly stimulates the metabolism of sphingolipids and the secretion of
      sphingosine-1-phosphate (S1P) in H295R cells. In this study, we examined the
      effect of S1P on genes involved in the acute phase of steroidogenesis. We show
      that S1P increases the expression of steroidogenic acute regulatory protein
      (StAR), 18-kDa translocator protein (TSPO), low-density lipoprotein receptor
      (LDLR), and scavenger receptor class B type I (SR-BI). S1P-induced StAR mRNA
      expression requires Galpha(i) signaling, phospholipase C (PLC), Ca(2+)/calmodulin
      dependent kinase II (CamKII), and ERK1/2 activation. S1P also increases
      intracellular Ca(2+), the phosphorylation of hormone sensitive lipase (HSL) at
      Ser(563), and cortisol secretion. Collectively, these findings identify multiple
      roles for S1P in the regulation of glucocorticoid biosynthesis.

PMID- 21864650
TI  - Lidocaine for prolonged and intensified spinal anesthesia by coadministration of
      propranolol in the rat.
AB  - Although the coadministration of lidocaine with propranolol interferes with the
      metabolic profile (pharmacokinetics), its pharmacodynamics is still unclear. In
      this report, we investigate whether propranolol can potentiate the effect of
      lidocaine. Rats received spinal anesthesia with lidocaine co-injected with
      propranolol. After intrathecal injections of drugs in rats, three neurobehavioral
      examinations (motor function, proprioception, and nociception) were performed. We
      showed that lidocaine and propranolol elicited a spinal blockade in motor
      function, proprioception, and nociception. Propranolol at the dose of 0.82
      MUmol/kg produced no spinal anesthesia. Co-administration of lidocaine [50%
      effective dose (ED(50)) or ED(95)] and propranolol (0.82 MUmol/kg) produced
      greater spinal anesthesia than lidocaine (ED(50) or ED(95)), respectively. These
      preclinical findings demonstrated that propranolol and lidocaine displayed spinal
      anesthesia. When combined with propranolol, lidocaine elicited a supra-additive
      effect of spinal anesthesia.

PMID- 21864652
TI  - Ginseng derivative ocotillol enhances neuronal activity through increased
      glutamate release: a possible mechanism underlying increased spontaneous
      locomotor activity of mice.
AB  - Ginsenosides are the main active ingredients in ginseng and have recently been
      reported to have beneficial effects on the CNS. Ocotillol is a derivate of
      pseudoginsenoside-F11, which is an ocotillol-type ginsenoside found in American
      ginseng. We examined the effects of ocotillol (a) on neuronal activity of
      projection neurons, mitral cells (MC), in a mouse olfactory bulb brain slice
      preparation using whole-cell patch-clamp recording, and (b) on animal behavior by
      measuring locomotor activity of mice in vivo. Ocotillol displayed an excitatory
      effect on spontaneous action potential firing and depolarized the membrane
      potential of MCs. The effect was concentration-dependent, with an EC(50) of 4
      MUM. In the presence of blockers of ionotropic glutamatergic and GABAergic
      synaptic transmission (6-cyano-7-nitroquinoxaline-2,3-dione [CNQX], 10 MUM; D
      AP5, 50 MUM; gabazine, 5 MUM), the excitatory effect of ocotillol on firing was
      abolished. Further experiments showed that the ocotillol-induced neuronal
      excitation persisted in the presence of GABA(A) receptor antagonist gabazine but
      was eliminated by applying AMPA/kainate receptor antagonist CNQX and N-methyl-d
      aspartate (NMDA) receptor antagonist D-AP5, suggesting that ionotropic glutamate
      transmission was involved in mediating the effects of ocotillol. Bath application
      of ocotillol evoked an inward current as well as an increased frequency of
      spontaneous glutamatergic excitatory postsynaptic currents (EPSCs). Both the
      inward current and sEPSCs could be blocked by ionotropic glutamate receptor
      antagonists CNQX and D-AP5. These results indicate that the excitatory action of
      ocotillol on MCs was mediated by enhanced glutamate release. Behavioral
      experiments demonstrated that ocotillol increased locomotor activities of mice.
      Our results suggest that ocotillol-evoked neuronal excitability was mediated by
      increased release of glutamate, which may be responsible for the increased
      spontaneous locomotor activities in vivo.

PMID- 21864653
TI  - The science of making drug-addicted animals.
AB  - Research involving animal models of drug addiction can be viewed as a sort of
      reverse psychiatry. Contrary to clinicians who seek to treat addicted people to
      become and remain abstinent, researchers seek to make drug-naive animals addicted
      to a drug with known addictive properties in humans. The goals of this research
      are to better understand the neuroscience of drug addiction and, ultimately, to
      translate this knowledge into effective treatments for people with addiction. The
      present review will not cover the vast literature that has accumulated over the
      past 50 years on animal models of drug addiction. It is instead more modestly
      devoted to recent research spanning the past decade on drug self-administration
      based models of addiction in the rat (the animal species most frequently used in
      the field), with a special focus on current efforts to model compulsive cocaine
      use as opposed to nonaddictive use. Surprisingly, it turns out that modeling
      compulsive cocaine use in rats is possible but more difficult than previously
      thought. In fact, it appears that resilience to cocaine addiction is the norm in
      rats. As in human cocaine users, only few individual rats would be vulnerable.
      This conclusion has several important implications for future research on the
      neuroscience of cocaine addiction and on preclinical medication development.

PMID- 21864651
TI  - Hereditary hemochromatosis and transferrin receptor 2.
AB  - BACKGROUND: Multicellular organisms regulate the uptake of calories, trace
      elements, and other nutrients by complex feedback mechanisms. In the case of
      iron, the body senses internal iron stores, iron requirements for hematopoiesis,
      and inflammatory status, and regulates iron uptake by modulating the uptake of
      dietary iron from the intestine. Both the liver and the intestine participate in
      the coordination of iron uptake and distribution in the body. The liver senses
      inflammatory signals and iron status of the organism and secretes a peptide
      hormone, hepcidin. Under high iron or inflammatory conditions hepcidin levels
      increase. Hepcidin binds to the iron transport protein, ferroportin (FPN),
      promoting FPN internalization and degradation. Decreased FPN levels reduce iron
      efflux out of intestinal epithelial cells and macrophages into the circulation.
      Derangements in iron metabolism result in either the abnormal accumulation of
      iron in the body, or in anemias. The identification of the mutations that cause
      the iron overload disease, hereditary hemochromatosis (HH), or iron-refractory
      iron-deficiency anemia has revealed many of the proteins used to regulate iron
      uptake. SCOPE OF THE REVIEW: In this review we discuss recent data concerning the
      regulation of iron homeostasis in the body by the liver and how transferrin
      receptor 2 (TfR2) affects this process. MAJOR CONCLUSIONS: TfR2 plays a key role
      in regulating iron homeostasis in the body. GENERAL SIGNIFICANCE: The regulation
      of iron homeostasis is important. One third of the people in the world are
      anemic. HH is the most common inherited disease in people of Northern European
      origin and can lead to severe health complications if left untreated. This
      article is part of a Special Issue entitled Transferrins: Molecular mechanisms of
      iron transport and disorders.

PMID- 21864654
TI  - Neuroprotective and neuroregenerative effects of low-intensity aerobic exercise
      on sciatic nerve crush injury in mice.
AB  - Here, we established a program of low-intensity aerobic exercise and compared the
      effects of exercise preoperative, postoperative, and a combination of both pre-
      and postoperative protocols on recovery from sciatic nerve crush injury in mice
      using behavioral, biochemical, and morphological assays. Sciatic nerve crush was
      performed in adult male mice. The animals were submitted to preoperative (for 2
      weeks), postoperative (for 2 weeks), and a combination of preoperative
      postoperative (for 4 weeks) training protocols. During the training period,
      functional recovery was monitored using the Sciatic Functional Index, the Sciatic
      Static Index, and mechanical and cold hypersensitivity analyses. Morphological
      and biochemical alterations were analyzed on the 14th day post-crushing. The
      functional recovery values of all of the exercised groups were significantly
      better than the nonexercised group. Biochemically, all of the exercise groups
      showed a reduction in the increase of interleukin-1beta (IL-1beta) in the sciatic
      nerve and in the IL-1beta and interleukin-6 receptor (IL-6R) levels in the spinal
      cord. However, the levels of tumor necrosis factor alpha (TNF-alpha) decreased
      only in the postoperative group and in the combination exercise protocols. In the
      morphological analysis, the combination exercise subjects presented an increase
      in fiber and axon diameter, in the myelination degree and in the number of
      myelinated fibers. The present study showed that pre- and postoperative exercise
      achieved values for functional and morphological sciatic nerve regeneration that
      were significantly better than either the preoperative or postoperative
      protocols. This experimental study suggests that physical exercise can restore
      motor and nerve function to a substantial degree when performed using a
      prophylactic and therapeutic approach.

PMID- 21864655
TI  - Involvement of spinal cord BDNF in the generation and maintenance of chronic
      neuropathic pain in rats.
AB  - Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and
      synaptic plasticity of the central and peripheral nervous system. In chronic
      pain, plastic changes in dorsal horn neurons contribute to a phenomenon of
      hypersensitivity to pain sensation that is maintained over time, known as central
      sensitization. This process is accompanied by BDNF overexpression, but the role
      of BDNF in the generation and maintenance of the hyperalgesic phenomenon is still
      unclear. The present study was aimed to investigate if exogenous BDNF
      administered to the rat spinal cord, in addition to trigger pain, participates in
      the maintenance of the central sensitization process (i.e., pain persistence) and
      to determine if the pain generated is comparable to that observed in a
      neuropathic pain model. Results showed that a single intrathecal injection of
      0.003 ng of BDNF was able to decrease the nociceptive threshold (Randall-Selitto
      test) in normal rats, for at least a 42-day period. Furthermore, the hyperalgesia
      generated was comparable to that observed in rats with a 42-day history of
      mononeuropathy. Increasing the dose or administering additional doses of BDNF
      resulted neither in additional effectiveness in reducing the pain threshold nor
      in the prolongation of the hyperalgesic effect, thus showing that central
      sensitization induced by BDNF is a dose-independent, all-or-none process. It is
      concluded that BDNF alone is sufficient for generating a long-lasting neural
      excitability change in the spinal cord via tyrosine kinase B receptor signaling,
      similar to that observed in chronic pain models such as neuropathy.

PMID- 21864656
TI  - Rats exhibit asymmetrical retention functions for hedonic samples.
AB  - Rats were trained in a symbolic delayed matching-to-sample task to discriminate
      hedonic sample stimuli that consisted of food or no food. Retention functions
      decreased more rapidly on trials initiated by a food sample than on trials
      initiated by a no-food sample when retention intervals were manipulated within
      session. The asymmetrical functions could not be explained in terms of mediation
      of choice responding by magazine head-entry behavior during the retention
      interval. Unlike within-session changes in retention interval, between-session
      changes did not result in steeper forgetting functions for food samples. These
      results in rats are consistent with previous findings reported for the presence
      and absence of visual samples in pigeons (Wixted, 1993).

PMID- 21864657
TI  - Ex vivo toxicity of nitrogen dioxide in human nasal epithelium at the WHO defined
      1-h limit value.
AB  - Current pollution limits indicating potential harm to human health caused by
      nitrogen dioxide have prompted a variety of studies on the cytotoxicity and
      genotoxicity of nitrogen dioxide (NO2) in vitro. The present study focuses on
      toxic effects of NO2 at the WHO defined 1-h limit value of 200 MUg NO2/m(3) air,
      equivalent to 0.1 ppm NO2. Nasal epithelial mucosa cells of 10 patients were
      cultured as an air-liquid interface and exposed to 0.1 ppm NO2 for 0.5 h, 1 h, 2
      h and 3 h and synthetic air as negative control. After exposure, analysis of
      genotoxicity was performed by the alkaline single cell microgel electrophoresis
      (comet) assay and by the micronucleus test. Depression of proliferation and
      cytotoxic effects were checked by the micronucleus assay and the trypan blue
      exclusion assay. The experiments demonstrated significant DNA fragmentation even
      at the shortest exposure duration of half an hour in the comet assay. The amount
      of DNA fragmentation significantly increased with extended NO2 exposure
      durations. The amount of DNA fragmentation increased with extended exposure
      durations to synthetic air at a significantly lower level as compared to NO2
      exposure. Micronucleus inductions were seen only at the longest exposure duration
      of 3h. There were no changes in proliferation seen in the micronucleus assay
      under any experimental setup. Moreover, no signs of necrosis, apoptosis or
      changes in viability were detected. Data demonstrate genotoxicity of NO2 at
      concentrations found in the urban atmosphere during short exposure durations. DNA
      alterations in the micronucleus assay at an exposure time of 3h indicate a
      significant DNA alteration possibly being hazardous to humans.

PMID- 21864658
TI  - Autofluorescence microscopy: a non-destructive tool to monitor mitochondrial
      toxicity.
AB  - Visualization of NADH by fluorescence microscopy makes it possible to distinguish
      mitochondria inside living cells, allowing structure analysis of these organelles
      in a non-invasive way. Mitochondrial morphology is determined by the occurrence
      of mitochondrial fission and fusion. During normal cell function mitochondria
      appear as elongated tubular structures. However, cellular malfunction induces
      mitochondria to fragment into punctiform, vesicular structures. This change in
      morphology is associated with the generation of reactive oxygen species (ROS) and
      early apoptosis. The aim of this study is to demonstrate that autofluorescence
      imaging of mitochondria in living eukaryotic cells provides structural and
      morphological information that can be used to assess mitochondrial health. We
      firstly established the illumination conditions that do not affect mitochondrial
      structure and calculated the maximum safe light dose to which the cells can be
      exposed. Subsequently, sequential recording of mitochondrial fluorescence was
      performed and changes in mitochondrial morphology were monitored in a continuous
      non-destructive way. This approach was then used to assess mitochondrial toxicity
      induced by potential toxicants exposed to mammalian cells. Both mouse and human
      cells were used to evaluate mitochondrial toxicity of different compounds with
      different toxicities. This technique constitutes a novel and promising approach
      to explore chemical induced toxicity because of its reliability to monitor
      mitochondrial morphology changes and corresponding toxicity in a non-invasive
      way.

PMID- 21864659
TI  - Differential effect of P-gp and MRP2 on cellular translocation of gemifloxacin.
AB  - Fluoroquinolones are broad spectrum antibiotics widely indicated in the treatment
      of both human and animal diseases. The primary objective of this study was to
      assess short and long term affinities of gemifloxacin towards efflux transporters
      (P-gp, MRP2) and nuclear hormone receptor (PXR). Uptake and dose dependent
      inhibition studies were performed with [(14)C] erythromycin (0.25 MUCi/ml) on
      MDCKII-MDR1 and MDCKII-MRP2 cells. Cellular accumulation of calcein-AM was
      further determined to confirm the affinity of gemifloxacin towards P-gp and MRP2.
      Transport studies were conducted to determine bi-directional permeability and to
      assess efflux ratio of gemifloxacin. LS-180 cells were treated with three
      different concentrations of gemifloxacin for 72 h and real-time PCR analysis was
      performed to study the quantitative gene expression levels of PXR, MDR1 and MRP2.
      Further, [(14)C] erythromycin uptake was also performed on LS-180 treated cells
      to better delineate the functional activity of efflux transporters. Results from
      our study suggest that gemifloxacin may be a substrate of both the efflux
      transporters studied. This compound inhibited both P-gp and MRP2 mediated efflux
      of [(14)C] erythromycin in a dose dependent manner with IC(50) values of 123 +/-
      2 MUM and 16 +/- 2 MUM, respectively. The efflux ratio of [(14)C] erythromycin
      lowered from 3.56 to 1.63 on MDCKII-MDR1 cells and 4.93 to 1.26 on MDCKII-MRP2
      cells. This significant reduction in efflux ratio further confirmed the substrate
      specificity of gemifloxacin towards P-gp and MRP2. Long term exposure
      significantly induced the expression of PXR (18 fold), MDR1 (6 fold) and MRP2 (6
      fold). A decrease (20%) in [(14)C] erythromycin uptake further confirmed the
      elevated functional activity of P-gp and MRP2. In conclusion, our studies
      demonstrated that gemifloxacin is effluxed by both P-gp and MRP2. Long term
      exposure induced their gene expression and functional activity. This substrate
      specificity of gemifloxacin towards these efflux transporters may be one of the
      major factors accounting for low oral bioavailability (71%). Better understanding
      of these mechanistic interactions may aid in the development of newer strategies
      to achieve adequate therapeutic levels and higher bioavailability.

PMID- 21864660
TI  - NMR imaging of chitosan and carboxymethyl starch tablets: swelling and hydration
      of the polyelectrolyte complex.
AB  - The hydration and swelling properties of the tablets made of chitosan,
      carboxymethyl starch, and a polyelectrolyte complex of these two polysaccharides
      have been studied by NMR imaging. We studied the effect of pH and ionic strength
      on the swelling of the tablets and on the diffusion of fluid into the tablets in
      water and simulated physiological fluids. The pH value of the fluids exerts a
      more significant effect than their ionic strengths on the swelling of the
      tablets. The tablets are compared also with those made of cross-linked high
      amylose starch. The formation of complex helps to keep the integrity of the
      tablets in various media and render a slow and restricted swelling similar to
      that of the tablets of the cross-linked high amylase starch, which is
      significantly lower than the swelling of chitosan and of carboxymethyl starch.
      The capacities to modulate the release rate of drugs in different media are
      discussed by comparing the matrices and evaluating the preparation process of the
      complex. A sustained release of less soluble drugs such as aspirin in
      gastrointestinal fluids can be provided by the complex, due to the ionic
      interaction and hydrogen bonding between the drug and the biopolymer complex.

PMID- 21864662
TI  - Enhanced dissolution of inhalable cyclosporine nano-matrix particles with
      mannitol as matrix former.
AB  - This study aims to improve the dissolution of inhalable cyclosporine A
      nanoparticles by formulating the drug with mannitol as a hydrophilic nano-matrix
      former. The effect of mannitol content on the aerosol performance of the nano
      matrix particles was also examined. Cyclosporine A nanosuspensions were produced
      by anti-solvent precipitation using a multi-inlet vortex mixer. Various amounts
      of mannitol were dissolved into the suspensions before spray drying to obtain
      micron-sized aggregates (nano-matrix powders). Dissolution properties of the
      powders in an aqueous medium, with the drug content, aggregate size distribution,
      surface roughness, physicochemical properties and aerosol performance were
      determined. The powders contained amorphous cyclosporine A and alpha-crystalline
      mannitol, with drug content being very close to the theoretical doses. Inclusion
      of mannitol enhanced the dissolution rate of the drug, without significantly
      affecting the aggregate size distribution, surface roughness and aerosol
      performance. This formulation approach may be applicable to improving the
      dissolution rate and bioavailability of hydrophobic drugs.

PMID- 21864661
TI  - PLGA nanoparticles loaded with the antileishmanial saponin beta-aescin: factor
      influence study and in vitro efficacy evaluation.
AB  - Colloidal carriers are known to improve the therapeutic index of the conventional
      drugs in the treatment of visceral leishmaniasis (VL) by decreasing their
      toxicity whilst maintaining or increasing therapeutic efficacy. This paper
      describes the development of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles
      (NPs) for the antileishmanial saponin beta-aescin. NPs were prepared by the W/O/W
      emulsification solvent evaporation technique and the influence of five
      preparation parameters on the NPs' size (Z(ave)), zeta potential and entrapment
      efficiency (EE%) was investigated using a 2(5-2) fractional factorial design.
      Cytotoxicity of aescin, aescin-loaded and blank PLGA NPs was evaluated in J774
      macrophages and non-phagocytic MRC-5 cells, whereas antileishmanial activity was
      determined in the Leishmania infantum ex vivo model. The developed PLGA NPs were
      monodispersed with Z(ave)<500 nm and exhibited negative zeta potentials. The
      process variables 'surfactant primary emulsion', 'concentration aescin' and
      'solvent evaporation rate' had a positive effect on EE%. Addition of Tween 80 to
      the inner aqueous phase rendered the primary emulsion more stable, which in its
      turn led to better saponin entrapment. The selectivity index (SI) towards the
      supporting host macrophages increased from 4 to 18 by treating the cells with
      aescin-loaded NPs instead of free beta-aescin. In conclusion, the in vitro
      results confirmed our hypothesis.

PMID- 21864663
TI  - Thermal processing of a poorly water-soluble drug substance exhibiting a high
      melting point: the utility of KinetiSol(r) Dispersing.
AB  - Poorly water-soluble drug substances that exhibit high melting points are often
      difficult to successfully process by fusion-based techniques. The purpose of this
      study was to identify a suitable polymer system for meloxicam (MLX), a high
      melting point class II BCS compound, and investigate thermal processing
      techniques for the preparation of chemically stable single phase solid
      dispersions. Thermal and solution based screening techniques were utilized to
      screen hydrophilic polymers suitable for immediate release formulations. Results
      of the screening studies demonstrated that Soluplus((r))(SOL) provided the
      highest degree of miscibility and solubility enhancement. A hot-melt extrusion
      feasibility study demonstrated that high temperatures and extended residence
      times were required in order to render compositions amorphous, causing
      significant degradation of MLX. A design of experiments (DOE) was conducted on
      the KinetiSol((r)) Dispersing (KSD) process to evaluate the effect of processing
      conditions on the chemical stability and amorphous character of MLX. The study
      demonstrated that ejection temperature significantly impacted MLX stability. All
      samples prepared by KSD were substantially amorphous. Dissolution analysis of the
      KSD processed solid dispersions showed increased dissolution rates and extent of
      supersaturation over the marketed generic MLX tablets.

PMID- 21864664
TI  - Synthesis and characterization of mannosylated pegylated polyethylenimine as a
      carrier for siRNA.
AB  - Regulation of gene expression using small interfering RNA (siRNA) is a promising
      strategy for research and treatment of numerous diseases. In this study, we
      develop and characterize a delivery system for siRNA composed of polyethylenimine
      (PEI), polyethylene glycol (PEG), and mannose (Man). Cationic PEI complexes and
      compacts siRNA, PEG forms a hydrophilic layer outside of the polyplex for steric
      stabilization, and mannose serves as a cell binding ligand for macrophages. The
      PEI-PEG-mannose delivery system was constructed in two different ways. In the
      first approach, mannose and PEG chains are directly conjugated to the PEI
      backbone. In the second approach, mannose is conjugated to one end of the PEG
      chain and the other end of the PEG chain is conjugated to the PEI backbone. The
      PEI-PEG-mannose delivery systems were synthesized with 3.45-13.3 PEG chains and
      4.7-3.0 mannose molecules per PEI. The PEI-PEG-Man-siRNA polyplexes displayed a
      coarse surface in Scanning Electron Microscopy (SEM) images. Polyplex sizes were
      found to range from 169 to 357 nm. Gel retardation assays showed that the PEI-PEG
      mannose polymers are able to efficiently complex with siRNA at low N/P ratios.
      Confocal microscope images showed that the PEI-PEG-Man-siRNA polyplexes could
      enter cells and localized in the lysosomes at 2h post-incubation. Pegylation of
      the PEI reduced toxicity without any adverse reduction in knockdown efficiency
      relative to PEI alone. Mannosylation of the PEI-PEG could be carried out without
      any significant reduction in knockdown efficiency relative to PEI alone.
      Conjugating mannose to PEI via the PEG spacer generated superior toxicity and
      gene knockdown activity relative to conjugating mannose and PEG directly onto the
      PEI backbone.

PMID- 21864665
TI  - Effect of aqueous extract of the leaves of Acalypha wilkesiana 'Godseffiana'
      Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular
      indices of oxidative stress in alloxan induced diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Acalypha wilkesiana are used in
      Southern Nigeria for the management of hypertension and diabetes mellitus. In
      this study, the effect of aqueous extract of the leaves of Acalypha wilkesiana on
      the hematology, plasma biochemistry and ocular indices of oxidative stress was
      investigated in alloxan induced diabetic rats. METHODOLOGY: Diabetes mellitus was
      induced by injection of alloxan (80 mg/kg body weight), via the tail vein. The
      extract was administered orally at 100, 200 and 300 mg/kg (both to normal and
      diabetic rats), and metformin at 50mg/kg. RESULTS: On gas chromatographic
      analysis of the extract, twenty nine known flavonoids were detected, consisting
      mainly of 29.77% apigenin, 14.97% quercetin, 11.12% naringenin, 10.62%
      kaempferol, 9.05% (-)-epicatechin and 4.04% (+)-catechin. Tannic acid and beta
      sitosterol were also detected. Compared to test control, the treatment lowered
      (significantly, P < 0.05) plasma glucose, triglyceride, conjugated bilirubin
      levels, atherogenic index of plasma, plasma alanine transaminase activity, total
      protein and total bilirubin, aspartate transaminase activity and unconjugated
      bilirubin, plasma urea, blood urea nitrogen and ocular malondialdehyde contents,
      lymphocyte and monocyte counts, and not significantly, plasma very low density
      lipoprotein cholesterol, but increased (significantly, P < 0.05) plasma calcium
      contents, total white cell and platelet counts, mean cell volume and ocular
      ascorbic acid content, and (though not significantly) plasma high density
      lipoprotein cholesterol level, red cell and neutrophil counts. CONCLUSIONS: This
      study showed that the extract was hypoglycemic, positively affected the
      hemopoietic system and integrity and function (dose dependently) of the liver and
      kidney of the diabetic rats; improved the lipid profile and had no deleterious
      effect on red cell morphology. It also protected against oxidative stress in
      ocular tissues. This study also revealed the presence of pharmacologically active
      compounds in the leaf extract. All of these highlights the cardioprotective
      potential of the leaves of Acalypha wilkesiana and support its use in traditional
      health practices for the management of diabetes mellitus.

PMID- 21864666
TI  - Lonicera japonica Thunb.: ethnopharmacology, phytochemistry and pharmacology of
      an important traditional Chinese medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lonicera japonica Thunb. (Caprifoliaceae), a
      widely used traditional Chinese medicine, was known as Jin Yin Hua (Chinese: ),
      Ren Dong and Japanese honeysuckle. It was taken to treat the exopathogenic wind
      heat, epidemic febrile diseases, sores, carbuncles and some infectious diseases.
      At the same time, Lonicera japonica could be used as healthy food, cosmetics,
      ornamental groundcover, and so on. AIM OF THE REVIEW: The present paper reviewed
      the ethnopharmacology, the biological activities, toxicology and phytochemistry
      of Lonicera japonica. MATERIALS AND METHODS: Information on Lonicera japonica was
      gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS,
      Medline Plus, CNKI and Web of Science) and libraries. Additionally, information
      also was obtained from some local books and brilliant scholars on
      ethnopharmacology. RESULTS: More than 140 chemical compounds have been isolated,
      and the main compositions are essential oils, organic acids and flavones, etc.
      Lonicera japonica and its active principles possess wide pharmacological actions,
      such as anti-inflammatory, antibacterial, antiviral, antioxidative and
      hepatoprotective activities. CONCLUSIONS: As an important traditional Chinese
      medicine, further studies on Lonicera japonica can lead to the development of new
      drugs and therapeutics for various diseases, and how to utilize it better should
      be paid more attentions.

PMID- 21864667
TI  - Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric
      adenocarcinoma cells.
AB  - AIM OF THE STUDY: We had reported that Astragalus saponins (AST) exert promising
      anti-tumorigenic effects by suppressing the growth of HT-29 human colon cancer
      cells and tumor xenograft. In the present study, we further investigated the anti
      angiogenic property of AST in human gastric adenocarcinoma cells (AGS) and
      attempted to elucidate the underlying mechanism. MATERIALS AND METHODS: Viability
      of AGS cells was measured by using the MTT reduction method. Western blotting was
      performed to examine the effect of AST on apoptotic- and cell growth-related
      protein expression. Effect of AST on cell cycle progression was also evaluated
      using PI staining. A Matrigel invasion assay was then employed to demonstrate the
      effect of AST on the invasiveness of gastric cancer cells. The expression of
      invasion-associated proteins (VEGF and MMPs) was also investigated. RESULTS: AST
      could induce apoptosis in AGS cells by activating caspase 3 with subsequent
      cleavage of poly(ADP-ribose) polymerase. Besides, cell cycle arrest at the G2/M
      phase had been observed in AST-treated cells, leading to substantial growth
      inhibition. The anti-proliferative effect of AST was associated with the
      regulation of cyclin B1, p21 and c-myc. Results indicate that the number of AGS
      cells invaded through the Matrigel membrane was significantly reduced upon AST
      treatment, with concomitant down-regulation of the pro-angiogenic protein
      vascular endothelial growth factor (VEGF) as well as the metastatic proteins
      metalloproteinase (MMP)-2 and MMP-9. CONCLUSION: AST derived from the medicinal
      plant Astragalus membranaceus could modulate the invasiveness and angiogenesis of
      AGS cells besides its pro-apoptotic and anti-proliferative activities. These
      findings also suggest that AST has the potential to be further developed into an
      effective chemotherapeutic agent in treating advanced and metastatic gastric
      cancers.

PMID- 21864668
TI  - Vasorelaxant and hypotensive effects of a hydroalcoholic extract from the fruits
      of Nitraria sibirica Pall. (Nitrariaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Nitraria sibirica Pall. are
      traditionally used in Uighur medicine to treat hypertension. This study aimed to
      support that folk use by defining their vasoactive and hypotensive properties.
      MATERIALS AND METHODS: The vasorelaxant activity and the underlying mechanisms of
      a hydroalcoholic extract from the fruits of Nitraria sibirica Pall. (NSHE) were
      evaluated on thoracic aortic rings isolated from Wistar rats. In addition, the
      acute hypotensive effect of NSHE was assessed in anesthetized spontaneously
      hypertensive rats (SHR) and in their normotensive control Wistar Kyoto (WKY)
      rats. RESULTS: NSHE (0.1-10 g/l) was clearly more effective to induce
      vasodilation of phenylephrine- (PE, 1 MUM) than high KCl- (60mM) pre-contracted
      aortic rings with respective E(max) values of 82.9+/-2.2% and 34.8+/-3.6%. The
      removal of endothelium almost abolished the relaxant effect of the extract. In
      addition, pre-treatment with N(w)-nitro-L-arginine-methyl ester (L-NAME, 100
      MUM), atropine (1 MUM) or charybdotoxin (30 nM) plus apamin (30 nM), respective
      blockers of nitric oxide (NO) synthase, muscarinic receptors and endothelium
      derived hyperpolarizing factor (EDHF), significantly reduced the observed effect
      of NSHE. By contrast, the cyclooxygenase (COX) inhibitor indomethacin (10 MUM) or
      the K(+) channels blockers glibenclamide (10 MUM), iberiotoxin (30 nM) and 4
      amino-pyridine (4-AP, 1 mM) failed to modify the vasodilation. Finally, the acute
      intravenous injection of NSHE (1, 5, 10, 20 mg/kg) induced an immediate and
      transient hypotensive effect in anesthetized SHR and in WKY rats. CONCLUSIONS:
      This experimental animal study suggests that hydroalcoholic extract from the
      fruits of Nitraria sibirica Pall. induces vasorelaxation through an endothelium
      dependent pathway involving NO synthase (NOS) activation, EDHF production and
      muscarinic receptor stimulation. Additionally, our results determine that this
      vasorelaxant effect is translated by a significant hypotensive effect.

PMID- 21864669
TI  - Age and sex-related changes in rat brain mitochondrial oxidative status.
AB  - Mitochondria are the main source of free radical species and the most direct
      target for their damaging effects, which especially affect the brain
      mitochondrial function, which is better maintained by females than males. The aim
      of this work was to investigate the age-related changes in rat brain
      mitochondrial oxidative status focusing on sex differences. Male and female rat
      brain from four different age groups (6, 12, 18 and 24 months old) were analyzed.
      Oxidative damage accumulates in rat brain throughout aging, related to the
      increasing activity of mitochondrial respiratory chain (MRC) and failure of
      several antioxidant defenses. The aging effect was less marked in females, which
      accumulated less oxidative damage than males due in part to their greater
      antioxidant capacity, such as higher GPx activity and higher UCP5 level. This
      sexual dimorphism gradually increased during aging.

PMID- 21864670
TI  - Increased transvascular transport of WGA-peroxidase after chronic perinatal
      stress in the hippocampal microvasculature of the rat.
AB  - Brain endothelial ultrastructural properties contribute to maintain proper blood
      brain barrier (BBB) function. Several physiological and pathological conditions
      have been shown to alter BBB permeability to blood-borne molecules, acute and
      chronic stress among them. In the rat, early life stress increased transvascular
      transport of Evans blue, however, the route of tracer extravasation is not fully
      known; therefore the aim of the present experiment was to describe the
      ultrastructural changes in endothelial cells subsequent to chronic perinatal
      stress in order to ascertain the route for transvascular transport of an
      electrodense tracer. Pregnant Wistar rats and their litters were used. Four
      pregnant rats were subjected to forced swimming between gestational days 10 to
      20. After delivery, half of the control litters underwent 180 min maternal
      separation from postnatal day 2 to 20. Controls were kept free of any stress
      manipulation. At sacrifice between postnatal days 1 to 30 subjects were given
      intracardially the lectin wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP). WGA-HRP stained hippocampi were processed for
      ultrastructural analysis, transmission electron micrographs were obtained and
      endothelial ultrastructural parameters quantified using the ImageJ software. Both
      stress procedures accelerated gross microvessel development by decreasing
      capillary wall thickness and endothelial microvilli. However, early-life stress
      also neutralized endothelial glycocalyx, increased vesicle-mediated transport and
      tended to promote the formation of secondary lysosomes containing endocytosed WGA
      HRP vesicles, all parameters of altered endothelial cell function. Tight junction
      development in both stress groups was similar to the control pups.

PMID- 21864671
TI  - Shiga toxin 2 overexpression in Escherichia coli O157:H7 strains associated with
      severe human disease.
AB  - Variation in disease severity among Escherichia coli O157:H7 infections may
      result from differential expression of Shiga toxin 2 (Stx2). Eleven strains
      belonging to four prominent phylogenetic clades, including clade 8 strains
      representative of the 2006 U.S. spinach outbreak, were examined for stx2
      expression by real-time PCR and western blot analysis. Clade 8 strains were shown
      to overexpress stx2 basally, and following induction with ciprofloxacin when
      compared to strains from clades 1-3. Differences in stx2 expression generally
      correlated with Stx2 protein levels. Single-nucleotide polymorphisms identified
      in regions upstream of stx2AB in clade 8 strains were largely absent in non-clade
      8 strains. This study concludes that stx2 overexpression is common to strains
      from clade 8 associated with hemolytic uremic syndrome, and describes SNPs which
      may affect stx2 expression and which could be useful in the genetic
      differentiation of highly-virulent strains.

PMID- 21864673
TI  - 5-HT6 receptor ligands, EMD386088 and SB258585, differentially regulate 5-HT6
      receptor-independent events.
AB  - The serotonin 6 receptor (5-HT6R) is one of the most recently cloned receptors
      among the known serotonin receptors. Because it is abundantly distributed in the
      limbic region and is involved in neurological disorders, it has generated much
      interest as a drug discovery and a biological research target. However, several
      groups recently reported conflicting results for 5-HT6R ligands in animal
      studies. Herein, we investigated in vitro effects of 5-HT6R ligands in cultured
      neurons and mammalian cell lines to explain inconsistencies in the results of in
      vivo studies. When examined the effects of EMD386088, a 5-HT6R agonist, on cell
      viability, we found that EMD386088 potentiated cell death in cultured neuronal,
      native HEK293, and HEK/HA-5-HT6R cells. The results demonstrated that EMD386088
      induces its cytotoxic effects, regardless of the presence of 5-HT6Rs, by the
      downregulation of ERK1/2 activities. Furthermore, we studied the 5-HT6R
      independent effects of SB258585, a specific 5-HT6R antagonist. SB258585
      potentiated cell death and induced an increase in [Ca2+]i, whereas EMD386088 or 5
      HT did not affect [Ca2+]i. Because EMD386088 and SB258585 have been intensively
      used as 5-HT6R ligands in in vitro and in vivo studies, our findings suggest that
      these compounds should be used with caution in cell-based studies as well as
      behavioral studies.

PMID- 21864672
TI  - Mitochondrial permeability and toxicity of diethylhexyl and monoethylhexyl
      phthalates on TK6 human lymphoblasts cells.
AB  - Phthalates are ubiquitous compounds used in the manufacturing industry. Some are
      known endocrine disruptors, acting as xenoestrogens, others induce reproductive
      toxicity and damage to DNA among other effects. Studies on apoptosis induction
      and mitochondrial damage capacity of phthalates on the immune system are limited.
      This study aims to determine cell viability inhibition and apoptosis induction of
      diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) on the human
      TK6 lymphoblast cell line at concentrations found in the environment. Key
      hallmark events, such as mitochondrial membrane permeability, generation of
      reactive oxygen species (ROS) and activation of caspase 3 and 7 were measured.
      Concentrations that inhibit viability of 50% (IC50) of the cells were determined
      at 24, 48 and 72 h with doses ranging from 10 to 500 MUM. Changes in
      mitochondrial membrane permeability, ROS generation and activation of caspases 3
      and 7, were measured as part of the cell death mechanism. The IC50 at 24 h was
      approximately 250 MUM for both phthalates; at 48 h were 234 and 196 MUM for DEHP
      and MEHP, respectively and at 72 h IC50s were 100 and 80 MUM for DEHP and MEHP,
      respectively. Overall the longer the time of exposure the lower the IC50's for
      both compounds. Both compounds affected mitochondrial membrane potential,
      promoted ROS generation and activated caspases 3 and 7. MEHP is more toxic,
      promotes higher level of ROS production and caspases activation. Our findings
      suggest that DEHP and MEHP have the capacity to induce apoptosis in cells of the
      immune system at concentrations found in the environment.

PMID- 21864674
TI  - The inositol 5-phosphatase SHIP1 is a nucleo-cytoplasmic shuttling protein and
      enzymatically active in cell nuclei.
AB  - The inositol 5-phosphatase SHIP1 is a negative regulator of signaling processes
      in hematopoietic cells. SHIP1 mediates its regulatory function after
      relocalization from the cytoplasm to the plasma membrane where it converts its
      substrate PI(3,4,5)P(3) to PI(3,4)P(2) thereby terminating PI3-kinase mediated
      signaling. In addition, SHIP1 converts Ins(1,3,4,5)P(4) to Ins(1,3,4)P(3) thereby
      regulating inositol phosphate metabolism. Here we report, that SHIP1 can be
      detected in nuclear puncta of Jurkat cells by confocal microscopy after
      expression of SHIP1 from a tetracycline inducible vector. SHIP1-containing
      nuclear puncta partially co-localize with FLASH, a multifunctional nuclear
      protein that has been linked to apoptotic signaling and transcriptional control.
      Nuclear localization was confirmed for endogenously expressed SHIP1 in the
      myeloid leukemia cell line TF1. In addition, enzymatically active SHIP1 was found
      in nuclear fractions of Jurkat cells with a similar specific activity as
      cytoplasmic SHIP1. Further analysis revealed that SHIP1 is a nucleocytoplasmic
      shuttling protein which is actively imported into and exported out of the
      nucleus. Nuclear import is mediated by two canonical nuclear localization signals
      (NLS) i.e. K(327)KSK and K(547)KLR. Mutational inactivation of each NLS motif
      inhibited nuclear import and reduced the proliferation of cells indicating a
      functional role of nuclear SHIP1 for cell growth. Our data indicate that SHIP1 is
      partly localized in the nucleus and suggest that SHIP1 plays a role for nuclear
      phosphoinositide and/or nuclear inositol phosphate signaling.

PMID- 21864677
TI  - Mathematical modeling of drug delivery from one-layer and two-layer torus-shaped
      devices with external mass transfer resistance.
AB  - A mathematical modeling of controlled release of drug from one-layer and two
      layer torus-shaped devices with external mass transfer resistance is presented.
      Analytical solutions based on the pseudo-steady state approximation are derived.
      The validity of the equations is established in two stages. In the first stage,
      the validity of the models derived for more complex systems is determined by
      comparison with profiles predicted by the simplest model, in asymptotic cases. In
      the second stage, the reliability and usefulness of the models are ascertained by
      comparison of the simulation results with vaginal rings experimental release data
      reported in the literature. In order to measures quantitatively the fit of the
      theoretical models to the experimental data, the pair-wise procedure is used. A
      good agreement between the prediction of the models and the experimental data is
      observed. The models are applicable only to torus-shaped systems in where the
      initial load of drug is higher than its solubility in the polymer.

PMID- 21864675
TI  - Management of cytoskeleton architecture by molecular chaperones and
      immunophilins.
AB  - Cytoskeletal structure is continually remodeled to accommodate normal cell growth
      and to respond to pathophysiological cues. As a consequence, several cytoskeleton
      interacting proteins become involved in a variety of cellular processes such as
      cell growth and division, cell movement, vesicle transportation, cellular
      organelle location and function, localization and distribution of membrane
      receptors, and cell-cell communication. Molecular chaperones and immunophilins
      are counted among the most important proteins that interact closely with the
      cytoskeleton network, in particular with microtubules and microtubule-associated
      factors. In several situations, heat-shock proteins and immunophilins work
      together as a functionally active heterocomplex, although both types of proteins
      also show independent actions. In circumstances where homeostasis is affected by
      environmental stresses or due to genetic alterations, chaperone proteins help to
      stabilize the system. Molecular chaperones facilitate the assembly, disassembly
      and/or folding/refolding of cytoskeletal proteins, so they prevent aberrant
      protein aggregation. Nonetheless, the roles of heat-shock proteins and
      immunophilins are not only limited to solve abnormal situations, but they also
      have an active participation during the normal differentiation process of the
      cell and are key factors for many structural and functional rearrangements during
      this course of action. Cytoskeleton modifications leading to altered localization
      of nuclear factors may result in loss- or gain-of-function of such factors, which
      affects the cell cycle and cell development. Therefore, cytoskeletal components
      are attractive therapeutic targets, particularly microtubules, to prevent
      pathological situations such as rapidly dividing tumor cells or to favor the
      process of cell differentiation in other cases. In this review we will address
      some classical and novel aspects of key regulatory functions of heat-shock
      proteins and immunophilins as housekeeping factors of the cytoskeletal network.

PMID- 21864678
TI  - Enhanced bioavailability of nano-sized chitosan-atorvastatin conjugate after oral
      administration to rats.
AB  - A novel approach to improve the bioavailability and stability of atorvastatin
      (AT) was developed by constructing a nano-sized polymer-atorvastatin conjugate.
      Firstly, a novel chitosan-atorvastatin (CH-AT) conjugate was efficiently
      synthesized through amide coupling reaction. The formation of conjugate was
      confirmed by (1)H NMR and FT-IR spectrometry. Nano-sized conjugate with a mean
      size of 215.3+/-14.2 nm was prepared by the process of high pressure
      homogenization (HPH). Scanning electron microscopy (SEM) revealed that CH-AT nano
      conjugate possess smooth surface whereas X-ray diffraction (XRD) spectra
      demonstrated amorphous nature of nano-conjugate. Further, CH-AT nano-conjugate
      showed solubility enhancement of nearly 4-fold and 100-fold compared to CH-AT
      conjugate and pure AT, respectively. In vitro drug release studies in simulated
      gastric fluid and simulated intestinal fluid suggested sustained release of AT
      from the conjugate. Additionally, the nano-conjugate significantly reduced the
      acidic degradation of AT. The plasma-concentration time profile of AT after oral
      administration of CH-AT nano-conjugate (2574+/-95.4 ng/mL) to rat exhibited
      nearly 5-fold increase in bioavailability compared with AT suspension (583+/-55.5
      ng/mL). Finally, variable bioavailability, as observed for AT suspension was also
      reduced when AT was administered in form of CH-AT nano-conjugate. Taken together
      these data demonstrate that chitosan conjugate nano-prodrugs may be used as
      sustained polymeric prodrugs for enhancing bioavailability.

PMID- 21864679
TI  - In situ artificial membrane permeation assay under hydrodynamic control:
      correlation between drug in vitro permeability and fraction absorbed in humans.
AB  - The purpose of this study was to develop an in vitro permeation model that will
      predict the fraction of drugs absorbed in humans. A rotating-diffusion cell with
      two aqueous compartments, separated by a lipid-impregnated artificial membrane,
      was used to determine the permeability of drugs under conditions of controlled
      hydrodynamics. The measured effective permeability coefficient was modified to
      include the paracellular transport derived from a previously reported colorectal
      adenocarcinoma epithelial cell line (Caco-2) permeability study and the effects
      of unstirred water layer anticipated in vivo. Permeability data were collected
      for 31 different marketed drugs with known absolute oral bioavailability and
      human hepatic clearance data. Literature bioavailability values were corrected
      for the first pass hepatic clearance thus obtaining the fraction absorbed from
      intestinal lumen (fraction absorbed), F(a), while assuming that the fraction
      escaping intestinal extraction, F(g), was approximately ~1. Permeability obtained
      under conditions of controlled hydrodynamics was compared with the permeability
      measured under unstirred conditions. It is shown that the optimized effective
      permeability correlates with the fraction absorbed. In contrast, permeability
      data obtained under unstirred conditions does not show a good correlation. The in
      vitro permeation model developed in this study predicts the fraction absorbed of
      the selected drugs in humans within experimental uncertainty. It has been
      demonstrated that the correlation with the fraction absorbed is greatly improved
      using the permeability data obtained under controlled hydrodynamics with
      paracellular transport included in the model.

PMID- 21864676
TI  - Differential involvement of ezrin/radixin/moesin proteins in sphingosine 1
      phosphate-induced human pulmonary endothelial cell barrier enhancement.
AB  - Endothelial cell (EC) barrier dysfunction induced by inflammatory agonists is a
      frequent pathophysiologic event in multiple diseases. The platelet-derived
      phospholipid sphingosine-1 phosphate (S1P) reverses this dysfunction by potently
      enhancing the EC barrier through a process involving Rac GTPase-dependent
      cortical actin rearrangement as an integral step. In this study we explored the
      role of the ezrin, radixin, and moesin (ERM) family of actin-binding linker
      protein in modulating S1P-induced human pulmonary EC barrier enhancement. S1P
      induces ERM translocation to the EC periphery and promotes ERM phosphorylation on
      a critical threonine residue (Ezrin-567, Radixin-564, Moesin-558). This
      phosphorylation is dependent on activation of PKC isoforms and Rac1. The majority
      of ERM phosphorylation on these critical threonine residues after S1P occurs in
      moesin and ezrin. Baseline radixin phosphorylation is higher than in the other
      two ERM proteins but does not increase after S1P. S1P-induced moesin and ezrin
      threonine phosphorylation is not mediated by the barrier enhancing receptor S1PR1
      because siRNA downregulation of S1PR1 fails to inhibit these phosphorylation
      events, while stimulation of EC with the S1PR1-specific agonist SEW2871 fails to
      induce these phosphorylation events. Silencing of either all ERM proteins or
      radixin alone (but not moesin alone) reduced S1P-induced Rac1 activation and
      phosphorylation of the downstream Rac1 effector PAK1. Radixin siRNA alone, or
      combined siRNA for all three ERM proteins, dramatically attenuates S1P-induced EC
      barrier enhancement (measured by transendothelial electrical resistance (TER),
      peripheral accumulation of di-phospho-MLC, and cortical cytoskeletal
      rearrangement. In contrast, moesin depletion has the opposite effects on these
      parameters. Ezrin silencing partially attenuates S1P-induced EC barrier
      enhancement and cytoskeletal changes. Thus, despite structural similarities and
      reported functional redundancy, the ERM proteins differentially modulate S1P
      induced alterations in lung EC cytoskeleton and permeability. These results
      suggest that ERM activation is an important regulatory event in EC barrier
      responses to S1P.

PMID- 21864680
TI  - A thought experiment reconciling neuroscience and psychoanalysis.
AB  - Thought experiments have a long tradition in science. The thought experiment
      proposed in this article designs a brain that is compatible with a conceptual
      framework that integrates neuroscience and psychoanalysis. A connectionist model
      with emergent collective computational abilities is modified progressively and
      gradually to retrieve concepts such as the following: life instinct, the death
      instinct, the conscious, the preconscious, the unconscious, the free-association
      method, parapraxis, repetitive compulsion, repression, self, other, and "I". In
      this model, the process of memorisation is represented by a neural network with
      deep depressions, the bottoms of which correspond to learned configurations known
      as "attractors". This thought experiment could be helpful in suggesting new
      formulations of traditional psychoanalytic and neuroscientific constructs.

PMID- 21864681
TI  - Quality by design approach for developing chitosan-Ca-alginate microspheres for
      colon delivery of celecoxib-hydroxypropyl-beta-cyclodextrin-PVP complex.
AB  - The aim of the present work was to develop a new multiparticulate system,
      designed for colon-specific delivery of celecoxib for both systemic (in
      chronotherapic treatment of arthritis) and local (in prophylaxis of colon
      carcinogenesis) therapy. The system simultaneously benefits from ternary
      complexation with hydroxypropyl-beta-cyclodextrin and PVP (polyvinylpyrrolidone),
      to increase drug solubility, and vectorization in chitosan-Ca-alginate
      microspheres, to exploit the colon-specific carrier properties of these polymers.
      Statistical experimental design was employed to investigate the combined effect
      of four formulation variables, i.e., % of alginate, CaCl2, and chitosan and time
      of cross-linking on microsphere entrapment efficiency (EE%) and drug amount
      released after 4h in colonic medium, considered as the responses to be optimized.
      Design of experiment was used in the context of Quality by Design, which requires
      a multivariate approach for understanding the multifactorial relationships among
      formulation parameters. Doehlert design allowed for defining a design space,
      which revealed that variations of the considered factors had in most cases an
      opposite influence on the responses. Desirability function was used to attain
      simultaneous optimization of both responses. The desired goals were achieved for
      both systemic and local use of celecoxib. Experimental values obtained from the
      optimized formulations were in both cases very close to the predicted values,
      thus confirming the validity of the generated mathematical model. These results
      demonstrated the effectiveness of the proposed jointed use of drug cyclodextrin
      complexation and chitosan-Ca-alginate microsphere vectorization, as well as the
      usefulness of the multivariate approach for the preparation of colon-targeted
      celecoxib microspheres with optimized properties.

PMID- 21864682
TI  - Interstitial fibrosis is associated with increased COL1A2 transcription in AA
      injured renal tubular epithelial cells in vivo.
AB  - Accumulation of type I collagen is a key event in renal interstitial fibrosis. As
      there is no effective treatment, understanding the site where collagen is
      transcribed and the factors driving it in response to disease in vivo is critical
      for designing future therapies. The present research investigated the
      transcriptional activity of the COL1A2 gene in a mouse model of progressive
      fibrosis induced by aristolochic acid (aristolochic acid nephropathy, AAN). To
      achieve this we genetically modified mice to express a reporter gene (LacZ) and
      CCN2 (connective tissue growth factor) under the transcriptional control of the
      COL1A2 promoter /enhancer sequences. Using these mice we asked where is collagen
      actively transcribed and secondly, what is the role of CCN2 in AAN. Here, we
      report that de-novo transcription of the COL1A2 gene occurred predominantly in
      damaged tubular epithelial cells during progressive interstitial fibrosis in
      vivo. The activation of COL1A2 was studied by detection of the reporter gene LacZ
      and COL1A2 mRNA in interstitial, glomerular, vascular, and tubular epithelial
      tissue from laser capture microscopy. We also demonstrated that LacZ-positive
      cells co-express E-Cadherin a marker of epithelial origin which is consistent
      with an epithelial phenotype which is capable of collagen expression during
      injury. There was no evidence of detachment of these cells from tubules to become
      myofibroblasts. Moreover, we showed that the transgenic mice show a modest
      enhancement of CCN2 expression; however fibrosis induced by AA is the same in
      transgenics and controls suggesting that CCN2, at this level of expression, is
      not sufficient to enhance fibrogenesis. Overall our study provides a better
      understanding into the expression patterns and roles of two major extracellular
      matrix proteins: type I collagen and CCN2.

PMID- 21864683
TI  - Met-Lys-bradykinin-Ser-Ser, a peptide produced by the neutrophil from kininogen,
      is metabolically activated by angiotensin converting enzyme in vascular tissue.
AB  - Bradykinin (BK) is a vasoactive nonapeptide cleaved from circulating kininogens
      and that is degraded by angiotensin converting enzyme (ACE). It has been reported
      that the PR3 protease from human neutrophil releases an alternate peptide of 13
      amino acids, Met-Lys-BK-Ser-Ser, from high molecular weight kininogen. We have
      studied vascular actions of this kinin. Its affinity for recombinant B1 and B2
      receptors is very low, as assessed by the binding competition of [3H]Lys-des-Arg9
      BK and [3H]BK, respectively, but Met-Lys-BK-Ser-Ser effectively displaced a
      fraction of [3H]enalaprilat binding to recombinant ACE. Mutant recombinant ACE
      constructions revealed that affinity gap between BK and Met-Lys-BK-Ser-Ser is
      larger for the N-terminal catalytic site than for the C-terminal one, based on
      competition for the substrate Abz-Phe-Arg-Lys(Dnp)-Pro-OH in an enzymatic assay.
      Met-Lys-BK-Ser-Ser is a low potency stimulant of the rabbit aorta (bioassay for
      B1 receptors), but the human isolated umbilical vein, a contractile bioassay for
      the B2 receptors, responded to Met-Lys-BK-Ser-Ser more than expected from the
      radioligand binding assay, this agonist being ~30-fold less potent than BK in the
      vein. Venous tissue treatment with the ACE inhibitor enalaprilat reduced the
      apparent potency of Met-Lys-BK-Ser-Ser by 15-fold, while not affecting that of
      BK. In the rabbit isolated jugular vein, Met-Lys-BK-Ser-Ser is nearly as potent
      as BK as a contractile stimulant of endogenous B2 receptors (EC50 values of 16.3
      and 10.5 nM, respectively), but enalaprilat reduced the potency of Met-Lys-BK-Ser
      Ser 13-fold while increasing that of BK 5.3-fold. In vascular tissue, ACE assumes
      a paradoxical activating role for Met-Lys-BK-Ser-Ser.

PMID- 21864684
TI  - Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces
      oxidative stress, lipoperoxidation and TNFalpha-mediated apoptosis in rat liver.
AB  - Liver toxicity is one of the consequences of ecstasy (3,4
      methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported
      after MDMA consumption. Various factors probably play a role in ecstasy-induced
      hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters,
      the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive
      hepatic metabolism that involves the production of reactive metabolites which
      form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-alpha can
      promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of
      pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-kappaB, Bcl
      2) proteins. The aim of the present study was to obtain evidence for the
      oxidative stress mechanism and apoptosis involved in ecstasy-induced
      hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration.
      Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide
      dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and
      malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat
      liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment
      included decrease of GR and GPx activities (29% and 25%, respectively) and
      GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy
      administration compared to control rats. Liver cytosolic level of AA was
      increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong
      positive reaction for TNFalpha (p<0.001) in hepatocytes and a diffuse apoptotic
      process in the liver specimens (p<0.001). There was correlation between
      immunohistochemical results and Western blotting which were quantitatively
      measured by densitometry, confirming the strong positivity for TNF-alpha
      (p<0.001) and NF-kappaB (p<0.001); weak and intense positivity reactions was
      confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The
      results obtained in the present study suggest that MDMA induces loss of GSH
      homeostasis, decreases antioxidant enzyme activities, and lipoperoxidation that
      causes an oxidative stress that accompaines the MDMA-induced apoptosis in liver
      cells.

PMID- 21864685
TI  - Estrogen induces neurite outgrowth via Rho family GTPases in neuroblastoma cells.
AB  - Estrogen (E2) has direct in vivo and in vitro effects, such as inducing neurite
      outgrowth, on neurons. We investigated the morphological changes and
      intracellular signaling pathway induced by E2 in neuroblastoma (SH-SY5Y) cells.
      The effect of medroxyprogesterone acetate (MPA) or progesterone (P4) on the E2
      induced neurite outgrowth was also examined using SH-SY5Y cells. Neurite
      outgrowth was induced by E2 in association with the phosphorylation of Akt, and
      these effects of E2 were abolished by MPA but not by P4. Progesterone receptor
      antagonist RU486 blocked the inhibitory effects of MPA. Estrogen receptor
      antagonist ICI 182,780 and phosphatidylinositol 3-kinase inhibitor LY294002
      inhibited the E2-induced neurite outgrowth. Because the Rho family of small
      GTPases has been shown to be involved in the regulation of neurite outgrowth, we
      examined the cross-talk among Rac1, Cdc42 and RhoA in the E2-induced neurite
      outgrowth. E2 immediately increased the Rac1 and Cdc42 activity and decreased the
      RhoA activity. E2-induced neurite outgrowth was attenuated in cells expressing
      dominant-negative mutants for Rac1 or Cdc42. These results suggest that
      regulation of Rho family GTPase activity by E2 is important for the neurite
      outgrowth in neuroblastoma cells, and that MPA may have an antagonistic effect
      against E2.

PMID- 21864686
TI  - Factors affecting recombinant Western equine encephalitis virus glycoprotein
      production in the baculovirus system.
AB  - In an effort to produce processed, soluble Western equine encephalitis virus
      (WEEV) glycoproteins for subunit therapeutic vaccine studies, we isolated twelve
      recombinant baculoviruses designed to express four different WEEV glycoprotein
      constructs under the transcriptional control of three temporally distinct
      baculovirus promoters. The WEEV glycoprotein constructs encoded full-length E1,
      the E1 ectodomain, an E26KE1 polyprotein precursor, and an artificial, secretable
      E2E1 chimera. The three different promoters induced gene expression during the
      immediate early (ie1), late (p6.9), and very late (polh) phases of baculovirus
      infection. Protein expression studies showed that the nature of the WEEV
      construct and the timing of expression both influenced the quantity and quality
      of recombinant glycoprotein produced. The full-length E1 product was insoluble,
      irrespective of the timing of expression. Each of the other three constructs
      yielded soluble products and, in these cases, the timing of expression was
      important, as higher protein processing efficiencies were generally obtained at
      earlier times of infection. However, immediate early expression did not yield
      detectable levels of every WEEV product, and expression during the late (p6.9) or
      very late (polh) phases of infection provided equal or higher amounts of
      processed, soluble product. Thus, while earlier foreign gene expression can
      provide higher recombinant glycoprotein processing efficiencies in the
      baculovirus system, in the case of the WEEV glycoproteins, earlier expression did
      not provide larger amounts of high quality, soluble recombinant glycoprotein
      product.

PMID- 21864687
TI  - Single-particle reconstruction using L(2)-gradient flow.
AB  - In this paper, we present an iterative algorithm for reconstructing a three
      dimensional density function from a set of two dimensional electron microscopy
      images. By minimizing an energy functional consisting of a fidelity term and a
      regularization term, an L(2)-gradient flow is derived. The flow is integrated by
      a finite element method in the spatial direction and an explicit Euler scheme in
      the temporal direction. Our method compares favorably with those of the weighted
      back projection, Fourier method, algebraic reconstruction technique and
      simultaneous iterative reconstruction technique.

PMID- 21864688
TI  - Automated detection of amnestic mild cognitive impairment in community-dwelling
      elderly adults: a combined spatial atrophy and white matter alteration approach.
AB  - Amnestic mild cognitive impairment (aMCI) is a syndrome widely considered to be
      prodromal Alzheimer's disease. Accurate diagnosis of aMCI would enable earlier
      treatment, and could thus help minimize the prevalence of Alzheimer's disease.
      The aim of the present study was to evaluate a magnetic resonance imaging-based
      automated classification schema for identifying aMCI. This was carried out in a
      sample of community-dwelling adults aged 70-90 years old: 79 with a clinical
      diagnosis of aMCI and 204 who were cognitively normal. Our schema was novel in
      using measures of both spatial atrophy, derived from T1-weighted images, and
      white matter alterations, assessed with diffusion tensor imaging (DTI) tract
      based spatial statistics (TBSS). Subcortical volumetric features were extracted
      using a FreeSurfer-initialized Large Deformation Diffeomorphic Metric Mapping
      (FS+LDDMM) segmentation approach, and fractional anisotropy (FA) values obtained
      for white matter regions of interest. Features were ranked by their ability to
      discriminate between aMCI and normal cognition, and a support vector machine
      (SVM) selected an optimal feature subset that was used to train SVM classifiers.
      As evaluated via 10-fold cross-validation, the classification performance
      characteristics achieved by our schema were: accuracy, 71.09%; sensitivity,
      51.96%; specificity, 78.40%; and area under the curve, 0.7003. Additionally, we
      identified numerous socio-demographic, lifestyle, health and other factors
      potentially implicated in the misclassification of individuals by our schema and
      those previously used by others. Given its high level of performance, our
      classification schema could facilitate the early detection of aMCI in community
      dwelling elderly adults.

PMID- 21864689
TI  - Anticorrelated resting-state functional connectivity in awake rat brain.
AB  - Resting-state functional connectivity (RSFC) measured by functional magnetic
      resonance imaging has played an essential role in understanding neural circuitry
      and brain diseases. The vast majority of RSFC studies have been focused on
      positive RSFC, whereas our understanding about its conceptual counterpart -
      negative RSFC (i.e. anticorrelation) - remains elusive. To date, anticorrelated
      RSFC has yet been observed without the commonly used preprocessing step of global
      signal correction. However, this step can induce artifactual anticorrelation
      (Murphy et al., 2009), making it difficult to determine whether the observed
      anticorrelation in humans is a processing artifact (Fox et al., 2005). In this
      report we demonstrated robust anticorrelated RSFC in a well characterized
      frontolimbic circuit between the infralimbic cortex (IL) and amygdala in the
      awake rat. This anticorrelation was anatomically specific, highly reproducible
      and independent of preprocessing methods. Interestingly, this anticorrelated
      relationship was absent in anesthetized rats even with global signal correction,
      further supporting its functional significance. Establishing negative RSFC
      independent of data preprocessing methods will significantly enhance the
      applicability of RSFC in better understanding neural circuitries and brain
      networks. In addition, combining the neurobiological data of the IL-amygdala
      circuit in rodents, the finding of the present study will enable further
      investigation of the neurobiological basis underlying anticorrelation.

PMID- 21864690
TI  - Comparing dynamic causal models using AIC, BIC and free energy.
AB  - In neuroimaging it is now becoming standard practise to fit multiple models to
      data and compare them using a model selection criterion. This is especially
      prevalent in the analysis of brain connectivity. This paper describes a
      simulation study which compares the relative merits of three model selection
      criteria (i) Akaike's Information Criterion (AIC), (ii) the Bayesian Information
      Criterion (BIC) and (iii) the variational Free Energy. Differences in performance
      are examined in the context of General Linear Models (GLMs) and Dynamic Causal
      Models (DCMs). We find that the Free Energy has the best model selection ability
      and recommend it be used for comparison of DCMs.

PMID- 21864691
TI  - Genetic diversification without obvious genitalic morphological divergence in
      harvestmen (Opiliones, Laniatores, Sclerobunus robustus) from montane sky islands
      of western North America.
AB  - The southern Rocky Mountains and adjacent Intermontane Plateau Highlands region
      of western North America is a geographically diverse area with an active geologic
      history. Given the topological complexity and extensive geologic activity,
      organisms inhabiting this region are expected to show some degree of
      morphological and genetic divergence, especially populations found on the
      southern montane 'sky islands' of this region. Here we examine the
      phylogeographic history and diversification of a montane forest inhabiting
      harvestmen, Sclerobunus robustus, using a combination of genetic and
      morphological data. Divergence time estimates indicate that much of the
      diversification within and between major groups S. robustus predate the
      Pleistocene glacial cycles. The most widespread subspecies, Sclerobunus robustus
      robustus, is recovered as six genetically distinct, geographically cohesive
      mitochondrial phylogroups. Gene tree data for a single nuclear gene reveals
      congruent, albeit slightly more conservative, patterns of genetic divergence.
      Despite high levels of genetic divergence throughout their distribution,
      phylogroups show extreme conservation in somatic and reproductive morphology.
      This uncoupling of morphological and genetic differentiation may be due to
      morphological conservatism associated with a conserved microhabitat preference.
      Based on these data, it is obvious that S. robustus has undergone some level of
      cryptic diversification.

PMID- 21864692
TI  - Can sensitivity analysis help to detect long-branch attraction?
AB  - The behavior of nodal support and stability in the presence of long branches were
      examined under simulations and an analysis of real data. Relatively short
      branches were typically correctly resolved, received high bootstrap support, and
      were stable in sensitivity analyses. Longer branches received lower support and
      stability measures, and were often incorrectly resolved due to the long-branch
      attraction. Support and stability does not always correlate, and in the case of
      mammalian mitochondrial tree, well supported but unstable nodes were typically
      associated with long-branch attraction. Very long branches, on the other hand,
      may be incorrectly resolved with high support and stability indices. These
      patterns were observed both in simulations, and in the real data. The results
      indicate that sensitivity analysis may help to reveal phylogenetic uncertainty
      hidden behind artificially high support.

PMID- 21864693
TI  - A close relationship between primary nucleotides sequence structure and the
      composition of functional genes in the genome of prokaryotes.
AB  - Comparative genomics is an essential tool to unravel how genomes change over
      evolutionary time and to gain clues on the links between functional genomics and
      evolution. In prokaryotes, the large, good quality, genome sequences available in
      public databases and the recently developed large-scale computational methods,
      offer an unprecedent view on the ecology and evolution of microorganisms through
      comparative genomics. In this work, we examined the links among genome structure
      (i.e., the sequential distribution of nucleotides itself by detrended fluctuation
      analysis, DFA) and genomic diversity (i.e., gene functionality by Clusters of
      Orthologous Genes, COGs) in 828 full sequenced prokaryotic genomes from 548
      different bacteria and archaea species. DFA scaling exponent alpha indicated
      persistent long-range correlations (fractality) in each genome analyzed. Higher
      resolution power was found when considering the sequential succession of purine
      (AG) vs. pyrimidine (CT) bases than either keto (GT) to amino (AC) forms or
      strongly (GC) vs. weakly (AT) bonded nucleotides. Interestingly, the phyla
      Aquificae, Fusobacteria, Dictyoglomi, Nitrospirae, and Thermotogae were closer to
      archaea than to their bacterial counterparts. A strong significant correlation
      was found between scaling exponent alpha and COGs distribution, and we
      consistently observed that the larger alpha the more heterogeneous was the gene
      distribution within each functional category, suggesting a close relationship
      between primary nucleotides sequence structure and functional genes composition.

PMID- 21864694
TI  - The uncultured luminous symbiont of Anomalops katoptron (Beryciformes:
      Anomalopidae) represents a new bacterial genus.
AB  - Flashlight fishes (Beryciformes: Anomalopidae) harbor luminous symbiotic bacteria
      in subocular light organs and use the bacterial light for predator avoidance,
      feeding, and communication. Despite many attempts anomalopid symbionts have not
      been brought into laboratory culture, which has restricted progress in
      understanding their phylogenetic relationships with other luminous bacteria,
      identification of the genes of their luminescence system, as well as the nature
      of their symbiotic interactions with their fish hosts. To begin addressing these
      issues, we used culture-independent analysis of the bacteria symbiotic with the
      anomalopid fish, Anomalops katoptron, to characterize the phylogeny of the
      bacteria and to identify the genes of their luminescence system including those
      involved in the regulation of luminescence. Analysis of the 16S rRNA, atpA, gapA,
      gyrB, pyrH, recA, rpoA, and topA genes resolved the A. katoptron symbionts as a
      clade nested within and deeply divergent from other members of Vibrionaceae. The
      bacterial luminescence (lux) genes were identified as a contiguous set
      (luxCDABEG), as found for the lux operons of other luminous bacteria.
      Phylogenetic analysis based on the lux genes confirmed the housekeeping gene
      phylogenetic placement. Furthermore, genes flanking the lux operon in the A.
      katoptron symbionts differed from those flanking lux operons of other genera of
      luminous bacteria. We therefore propose the candidate name Candidatus Photodesmus
      (Greek: photo = light, desmus = servant) katoptron for the species of bacteria
      symbiotic with A. katoptron. Results of a preliminary genomic analysis for genes
      regulating luminescence in other bacteria identified only a Vibrio harveyi-type
      luxR gene. These results suggest that expression of the luminescence system might
      be continuous in P. katoptron.

PMID- 21864695
TI  - Molecular phylogeny and systematics of the highly polymorphic Rumex
      bucephalophorus complex (Polygonaceae).
AB  - Rumex bucephalophorus is a very polymorphic species that has been subjected to
      various taxonomic studies in which diverse infraspecific taxa have been
      recognised on the basis of diaspore traits. In this study we used molecular
      markers (ITS and AFLP) to explore this remarkable diversity, to test previous
      hypotheses of classification, and attempt to explain biogeographic patterns.
      Results show that R. bucephalophorus forms a monophyletic group in which
      diversification began around 4.2 Mya, at the end of Messinian Salinity Crisis.
      The two molecular markers clearly show a deep divergence separating subsp.
      bucephalophorus from all other subspecific taxa, among which subsp. canariensis
      also constitutes a separate and well distinguishable unit. In contrast,
      subspecies hispanicus and subsp. gallicus constitute a monophyletic group in
      which three subgroups can be recognised: subsp. hispanicus, subsp. gallicus var.
      gallicus and subsp. gallicus var. subaegeus. However, these three subgroups are
      not clearly distinguished genetically or morphologically, so that in formal
      classification it would be preferable to treat them at the varietal level.

PMID- 21864696
TI  - Phylogeny of the Southeast Asian freshwater fish genus Pangio (Cypriniformes;
      Cobitidae).
AB  - The genus Pangio is one of the most species-rich of the loach family Cobitidae
      and widespread across South and Southeast Asia. Its species diversity has never
      been studied under a clear phylogenetic approach, but four 'species-groups' were
      proposed according to the most obvious morphological characters. We present here
      phylogenetic analyses of the genus Pangio based on sequence data of the
      mitochondrial cytochrome b gene, the nuclear recombination-activating gene 1 (RAG
      1) and a combined dataset of 109 specimens from 18 morphologically identified
      species across the whole distribution area of the genus. Our data reveal the
      existence of three major lineages within Pangio. Two of our major lineages were
      congruent with formerly proposed species-groups, the remaining two species-groups
      together formed the third major lineage; herein we refer to the lineages as to
      anguillaris-group, kuhlii-oblonga group and shelfordii-group. The application of
      a molecular clock dated the age of the three lineages to 33-29 million years. At
      the species level, our data suggest about 30 distinct lineages, indicating that
      there is a high number of undescribed species within Pangio. The use of Pangio to
      address biogeographic questions is demonstrated with the example of the
      shelfordii-group, which is distributed across Sundaland.

PMID- 21864697
TI  - Phylogeny of the African and Asian Phortica (Drosophilidae) deduced from nuclear
      and mitochondrial DNA sequences.
AB  - Phylogenetic relationships of 26 Phortica species were investigated based on DNA
      sequence data of two mitochondrial (ND2, COI) and one nuclear (28S rRNA) genes.
      Five monophyletic groups were recovered in the genus Phortica, of which three
      were established as new subgenera, Alloparadisa, Ashima, and Shangrila. The
      subgenus Allophortica was suggested as the most basal lineage in Phortica,
      followed by the lineage of P. helva + P. sobodo + P. varipes. The remaining
      Phortica species, most of Oriental distribution, formed a monophyletic group, and
      were subdivided into three lineages (i.e., the subgenera Ashima, Phortica, and
      Shangrila). The subgenera Shangrila and Phortica were suggested as sister taxa,
      and four clades were recovered in the subgenus Ashima. The result of
      reconstruction of ancestral distribution and estimation of divergence times
      indicates that, the ancestor of the genus Phortica restricted to Africa, its
      initial diversification was dated back to ca. 23 Mya (coinciding with the
      Oligocene/Miocene boundary); sympatric speciation and an Africa-to-Asia dispersal
      was proposed to account for the current distribution of Allophortica and the rest
      Phortica; most of the rest diversification of Phortica occurred in southern
      China, and the divergence between the African clade and its Oriental counterpart
      was suggested as a result of vicariance following a dispersal of their ancestral
      species from southern China to Africa.

PMID- 21864698
TI  - Control of gene transcription by Mediator in chromatin.
AB  - The Mediator complex serves as an adaptor for regulatory factors, recruits and
      controls RNA polymerase II promotes preinitiation complex formation and functions
      post initiation. There is increasing evidence for further coordinating roles of
      the Mediator complex in chromatin. Here we summarize interactions with
      regulatory, general and accessory factors that function in transcription and
      chromatin.

PMID- 21864699
TI  - Post-translational modification of 14-3-3 isoforms and regulation of cellular
      function.
AB  - 14-3-3 is now well established as a family of dimeric proteins that can modulate
      interaction between proteins involved in a wide range of functions. In many
      cases, these proteins show a distinct preference for a particular isoform(s) of
      14-3-3 and in many cases a specific repertoire of dimer formation influences the
      particular proteins that 14-3-3 interact. Well over 200 proteins have been shown
      to interact with 14-3-3. The purpose of this review is to give an overview of the
      recently identified post-translational modifications of 14-3-3 isoforms and how
      this regulates function, interaction, specificity of dimerisation between
      isoforms and cellular location of target proteins. The association between 14-3-3
      and its targets usually involves phosphorylation of the interacting protein which
      has been the subject of many reviews and discussion of this is included in other
      reviews in this series. However, it is now realised that in some cases the
      phosphorylation and a number of other, novel covalent modifications of 14-3-3
      isoforms may modulate interaction and dimerisation of 14-3-3. Since this aspect
      is now emerging to be of major importance in the mechanism of regulation by 14-3
      3 isoforms and has not been the focus of previous reviews, this will be detailed
      here.

PMID- 21864700
TI  - In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of
      severe pneumococcal pneumonia.
AB  - KRP-109 is a novel specific inhibitor of neutrophil elastase (NE). Various
      studies suggest that NE inhibitors reduce lung injury associated with systemic
      inflammatory response syndrome (SIRS). In this study, the efficacy of KRP-109 was
      examined using a murine model of severe pneumonia induced by Streptococcus
      pneumoniae (S. pneumoniae). Female mice (CBA/J, aged 5 weeks) were inoculated
      intranasally with penicillin-susceptible S. pneumoniae (ATCC49619 strain, 2.5 *
      10(8) CFU/mouse). KRP-109 (30 or 50 mg/kg) or physiological saline as a control
      was administered intraperitoneally every 8 h beginning at 8 h after inoculation,
      and survival rate was evaluated over 7 days. Histopathological and
      bacteriological analyses of the lung, and bronchoalveolar lavage were performed
      at 48 h post-infection. The mice treated with KRP-109 (KRP-109 mice) tended to
      have higher survival rate than those given saline. The lung tissues of the KRP
      109 mice had few neutrophils in the alveolar walls and less inflammation.
      Furthermore, KRP-109 decreased significantly total cell and neutrophil counts,
      and cytokine levels (interleukin 1beta and macrophage inflammatory protein 2) in
      bronchoalveolar lavage fluid. Viable bacterial numbers in lung were not
      influenced by treatment of KRP-109. The present results indicate that KRP-109
      reduces lung inflammation in a murine model, and that KRP-109 may be useful for
      the treatment of patients with severe pneumonia.

PMID- 21864701
TI  - Sources of variation for nutritional condition indices of the plasma of migratory
      lesser kestrels in the breeding grounds.
AB  - Although published information on reference values for biochemical parameters in
      birds of prey has increased during the last years, little is known on their
      sources of variation. We used an insectivorous and small migratory raptor
      species, the lesser kestrel Falco naumanni, as a model. We looked for sources of
      variation of nutritional biochemical parameters (i.e. triglycerides, cholesterol,
      uric acid and urea) of both nestlings and adults. Reference values indicated
      that, as a rule, lesser kestrel showed more elevated triglycerides, urea and uric
      acid levels than other raptors. All analyzed factors except gender (i.e. year,
      colony, sampling time, presence/absence of a geolocator, body mass, laying date
      and capture date) reached significance for at least one biochemical parameter. In
      the morning, we found an important postprandial increase in the concentration of
      all biochemical parameters in nestlings, and uric acid and urea levels in adults.
      A positive relationship was detected between triglycerides and body mass in
      nestlings and adults. Although we did not find differences between blood
      biochemical parameters of the oldest and youngest chick of each brood, we found
      that cholesterol levels were lower in nestlings from larger broods. Coloration of
      tarsi (measured as brightness) was related to triglycerides and urea levels of
      nestlings and adults, respectively. The feeding habits of lesser kestrel probably
      explain the different levels and patterns of variation of metabolites in
      comparison to more carnivorous raptors eating mammals or birds.

PMID- 21864703
TI  - PGI2 as a regulator of CD4+ subset differentiation and function.
AB  - Prostaglandin (PG)I(2) has important regulatory functions on the innate and
      adaptive immune systems. Recent experimental evidence reveals that PGI(2)
      modulates the development and function of CD4+ T cells subsets, including Th1,
      Th2, and Th17 cell responses. In vitro and in vivo studies support that PGI(2)
      generally has an inhibitory effect on Th1 and Th2 activation, differentiation,
      and cytokine production. In contrast, PGI(2) seems to enhance Th17-favoring
      polarization conditions, resulting in Th17 cytokine production. Therefore, PGI(2)
      may either promote or inhibit individual CD4+ cell subsets and impact adaptive
      immune responses.

PMID- 21864702
TI  - Regulation of inflammation in cancer by eicosanoids.
AB  - Inflammation in the tumor microenvironment is now recognized as one of the
      hallmarks of cancer. Endogenously produced lipid autacoids, locally acting small
      molecule lipid mediators, play a central role in inflammation and tissue
      homeostasis, and have recently been implicated in cancer. A well-studied group of
      autacoid mediators that are the products of arachidonic acid metabolism include:
      the prostaglandins, leukotrienes, lipoxins and cytochrome P450 (CYP) derived
      bioactive products. These lipid mediators are collectively referred to as
      eicosanoids and are generated by distinct enzymatic systems initiated by
      cyclooxygenases (COX 1 and 2), lipoxygenases (5-LOX, 12-LOX, 15-LOXa, 15-LOXb),
      and cytochrome P450s, respectively. These pathways are the target of approved
      drugs for the treatment of inflammation, pain, asthma, allergies, and
      cardiovascular disorders. Beyond their potent anti-inflammatory and anti-cancer
      effects, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 specific
      inhibitors have been evaluated in both preclinical tumor models and clinical
      trials. Eicosanoid biosynthesis and actions can also be directly influenced by
      nutrients in the diet, as evidenced by the emerging role of omega-3 fatty acids
      in cancer prevention and treatment. Most research dedicated to using eicosanoids
      to inhibit tumor-associated inflammation has focused on the COX and LOX pathways.
      Novel experimental approaches that demonstrate the anti-tumor effects of
      inhibiting cancer-associated inflammation currently include: eicosanoid receptor
      antagonism, overexpression of eicosanoid metabolizing enzymes, and the use of
      endogenous anti-inflammatory lipid mediators. Here we review the actions of
      eicosanoids on inflammation in the context of tumorigenesis. Eicosanoids may
      represent a missing link between inflammation and cancer and thus could serve as
      therapeutic target(s) for inhibiting tumor growth.

PMID- 21864704
TI  - Effects of mycobacterial infection on proliferation of hematopoietic precursor
      cells.
AB  - Bacterial infection can affect hematopoietic precursor cells in bone marrow,
      because the infected tissues produce various cytokines and chemokines. Little is
      known about hematopoietic precursor cells, including hematopoietic stem cells and
      their progenitors, during mycobacterial infection. Here, we showed that
      mycobacterial infections result in the expansion of not only the lin-c-kit+sca-1+
      (LKS+) cell population, but also granulocyte-monocyte progenitor cells in a
      chronic murine tuberculosis model. Interestingly, stimulation of LKS+ cells with
      attenuated Mycobacterium tuberculosis H37Ra culture filtrate (RaCF) was
      significantly stronger than that by virulent H37Rv culture filtrate (RvCF). Lower
      TNF-alpha and IL-6 levels were observed in RvCF-stimulated bone marrow cells.
      Neutralization of TNF-alpha or IL-6 in RaCF-stimulated bone marrow cells markedly
      suppressed LKS+ cell clonal expansion. Additionally, numbers of LKS+ cells were
      lower in TLR2(-/-) and MyD88(-/-) mice after mycobacterial infection. Taken
      together, LKS+ cell proliferation related to mycobacterial virulence may be
      related to the secretion of TNF-alpha and IL-6 associated with TLR signaling.
      Expansion of hematopoietic progenitor cells may, therefore, play an important
      role during mycobacterial infection.

PMID- 21864705
TI  - Targeting angiogenesis with compounds from the extracellular matrix.
AB  - The extracellular matrix (ECM) is the central element of a pericellular network
      of bioactive molecules. It orchestrates molecular interactions, availability and
      activity, acting as a key regulator of cell functions and complex biological
      processes, including physiological and pathological angiogenesis. The ECM serves
      as a source of both stimulatory and inhibitory angiogenesis regulatory factors.
      The observation that several endogenous inhibitors of angiogenesis derive from
      the ECM proves its importance in physiological angiogenesis, and point to the ECM
      as a precious source of therapeutic agents for angiogenesis-driven diseases,
      including cancer growth and metastatic dissemination. This review focuses on the
      different approaches to exploit ECM molecules for designing tools for therapeutic
      inhibition or monitoring of pathological angiogenesis, with particular focus on
      antineoplastic therapy, and emphasis on peptides of ECM moieties and mimetic
      small molecules.

PMID- 21864706
TI  - BRCA1 is required for hMLH1 stabilization following doxorubicin-induced DNA
      damage.
AB  - Human DNA mismatch repair (MMR) is involved in the removal of DNA base mismatches
      that arise either during DNA replication or are caused by DNA damage. In this
      study, we show that the activation of the MMR component hMLH1 in response to
      doxorubicin (DOX) treatment requires the presence of BRCA1 and that this
      phenomenon is mediated by an ATM/ATR dependent phosphorylation of the hMLH1 Ser
      406 residue. BRCA1 is an oncosuppressor protein with a central role in the DNA
      damage response and it is a critical component of the ATM/ATR mediated checkpoint
      signaling. Starting from a previous finding in which we demonstrated that hMLH1
      is able to bind to BRCA1, in this study we asked whether BRCA1 might be the
      bridge for ATM/ATR dependent phosphorylation of the hMLH1 molecular partner. We
      found that: (i) the negative modulation of BRCA1 expression is able to produce a
      remarkable reversal of hMLH1 stabilization, (ii) BRCA1 is required for post
      translational modification produced by DOX treatment on hMLH1 which is, in turn,
      attributed to the ATM/ATR activity, (iii) the serine 406 phosphorylatable residue
      is critical for hMLH1 activation by ATM/ATR via BRCA1. Taken together, our data
      lend support to the hypothesis suggesting an important role of this
      oncosuppressor as a scaffold or bridging protein in DNA-damage response signaling
      via downstream phosphorylation of the ATM/ATR substrate hMLH1.

PMID- 21864707
TI  - Tumour necrosis factor-stimulated gene (TSG)-6 controls epithelial-mesenchymal
      transition of proximal tubular epithelial cells.
AB  - Progressive renal disease is characterized by accumulation of extracellular
      matrix in the renal cortex. Proximal tubular cells (PTC) may contribute to
      disease through a process of epithelial-mesenchymal-transition (EMT): phenotypic
      change, disruption of the tubular basement membrane and migration into the
      interstitium. Hyaluronan (HA) synthesis and its extracellular organization by
      hyaladherins affect cell fate in other systems: this study investigated the role
      of the hyaladherin, tumour necrosis factor-stimulated gene (TSG)-6, in PTC EMT
      triggered in vitro by transforming growth factor (TGF)beta1. TGFbeta1 triggered
      the loss of PTC epithelial phenotype with 60% decreased expression of E-cadherin
      and 2-3-fold induction of alpha-smooth muscle actin (alpha-sma). It also
      increased the expression of TSG-6, HA-synthase-(HAS)2 and the HA-receptor, CD44,
      to a peak at 8-12h, remaining elevated thereafter. Immuno-localization of HA
      demonstrated that unstimulated PTC assembled HA in cables and that treatment with
      TGFbeta1 initiated cable disassembly with formation of dense HA-pericellular
      coats. Stable knockdown of TSG-6 with short-hairpin-RNA increased E-cadherin and
      HAS2 expression, produced loose HA-pericellular coats, HA cables were absent and
      cell migration was slowed. Treatment of transfectants with TGFbeta1 did not
      induce alpha-sma, alter E-cadherin, pericellular-HA or migration but did induce
      HAS2. This was dependent on the expression of CD44 and was inhibited by CD44
      specific siRNA. In summary, TSG-6 was central to EMT through effects on HA
      macromolecular structure and through CD44-dependent triggering of cell responses.
      These findings suggest that controlling the assembly of HA by proximal tubular
      cells may be a novel approach towards intervention in renal disease.

PMID- 21864708
TI  - Nuclear translocation of Sgt1 depends on its phosphorylation state.
AB  - Recently we have shown that the Sgt1 (suppressor of G2 allele of Skp1) protein
      translocates to the nucleus due to heat shock and that the Ca(2+)-bound form of
      S100A6 is required for Sgt1 translocation (Prus and Filipek, 2010). In this work
      we studied the influence of Sgt1 phosphorylation on nuclear translocation. By
      means of two-dimensional (2D) electrophoresis we showed that in the protein
      extract of heat-shocked human epidermoid carcinoma (HEp-2) cells a higher level
      of a basic, most probably non-phosphorylated, form of Sgt1 can be detected. Also,
      we found a more efficient translocation of Sgt1 induced by heat shock when casein
      kinase II inhibitor was added to the cells. To confirm the role of Sgt1
      phosphorylation/dephosphorylation in its nuclear translocation we transfected
      cells with non-phosphorylable Sgt1 mutants (S249A, S299A, S249/299A) or a
      phosphorylation mimic S299D mutant. We found that the levels of S299A and
      S249/299A mutants were higher than the level of wild type Sgt1 in the nuclear
      fraction after heat shock. Accordingly, we found that the 139-333 fragment of
      Sgt1 harboring the mutated residues, but not the 1-138 fragment, translocated to
      the nucleus upon heat shock. Moreover, we show that S100A6 is required for
      translocation of the non-phosphorylable Sgt1 mutants and that upon heat shock
      S100A6 translocates to the nucleus together with Sgt1. In addition, we found that
      non-phosphorylable Sgt1 mutant interacts with S100A6 more efficiently and at the
      same time exhibits lower affinity for Hsp90 (heat shock protein 90) than wild
      type Sgt1. Altogether, our results suggest that S100A6-Ca(2+)-mediated Sgt1
      dephosphorylation promotes its nuclear translocation, most likely due to
      disruption of the Sgt1-Hsp90 complex.

PMID- 21864709
TI  - Novel advances in cytochrome P450 research.
AB  - The cytochrome P450 (CYP) enzymes, involved in the metabolism of therapeutic
      drugs, are the major determinants of drug half-life. From a drug industry
      perspective, variability in drug response owing to CYP polymorphisms makes CYP
      profiling a commercially interesting option for diagnosis, prognosis and
      predicting response to drug treatment. Recent studies highlighting microRNA
      mediated regulation of CYP genes represents a major advance in our understanding
      of variations in individual drug responses. Herein we review new perspectives on
      the molecular mechanisms of CYP regulation and genotyping technologies. Together,
      these developments present novel therapeutic opportunities and help to explain
      the integrated response of cells to xenobiotic drug metabolism.

PMID- 21864710
TI  - The role of fragment-based and computational methods in polypharmacology.
AB  - Polypharmacology-based strategies are gaining increased attention as a novel
      approach to obtaining potentially innovative medicines for multifactorial
      diseases. However, some within the pharmaceutical community have resisted these
      strategies because they can be resource-hungry in the early stages of the drug
      discovery process. Here, we report on fragment-based and computational methods
      that might accelerate and optimize the discovery of multitarget drugs. In
      particular, we illustrate that fragment-based approaches can be particularly
      suited for polypharmacology, owing to the inherent promiscuous nature of
      fragments. In parallel, we explain how computer-assisted protocols can provide
      invaluable insights into how to unveil compounds theoretically able to bind to
      more than one protein. Furthermore, several pragmatic aspects related to the use
      of these approaches are covered, thus offering the reader practical insights on
      multitarget-oriented drug discovery projects.

PMID- 21864711
TI  - Effects of Bayluscide on Bithynia siamensis goniomphalos, the first intermediate
      host of the human liver fluke, Opisthorchis viverrini, in laboratory and field
      trials.
AB  - The molluscicidal effects of Bayluscide (niclosamide) were investigated on
      Bithynia siamensis goniomphalos, the first intermediate host of human liver
      fluke, Opisthorchis viverrini. Lethal concentrations of 50% (LC(50)) and 95%
      (LC(95)) against young and adult males were 0.38 and 0.80, 0.42 and 0.86 ppm,
      respectively. The LC(50) and LC(95) against young and adult females were 0.42 and
      0.86, 0.46 and 0.97 ppm, respectively. No significant differences in mortality
      rate between sexes or snail size (p > 0.05) was detected. Bayluscide-related
      tissue damage in B. siamensis goniomphalos included detachment of cilia of the
      epithelial layer of the digestive tract and decreased number of calcium cells. In
      tests of lethal concentrations of Bayluscide on non-target animals, no lethal
      effect was observed on Filopaludina martensi martensi (Viviparous snail) but high
      mortality rates were recorded in Puntius gonionotus fingerling, Ricefish (Oryzias
      mekongensis) and shrimp (Macrobrachium lanchesteri), but lower in guppy fish
      (Poecilia reticulata) after 24h exposure. For field trials, sufficient Bayluscide
      was sprayed in 3 roadside ditches to result in final concentrations of 5, 10 or
      20 ppm, with mortality rates on B. siamensis goniomphalos of 10.94, 20.00 and
      31.25%, respectively. Non-target snails died in small numbers but no effect was
      observed in other aquatic vertebrate animals. Field trials of Bayluscide on B.
      siamensis goniomphalos revealed low mortality rates, suggesting the need for
      application methods of higher efficacy or that Bayluscide is not suitable for
      application to operculate snails or snails which are able to escape by burying in
      mud.

PMID- 21864712
TI  - Coproantigen capture ELISA for detection of Clonorchis sinensis infection in
      experimentally infected rats.
AB  - The present study investigated the diagnostic value of an ELISA for the detection
      of Clonorchis sinensis antigen in the feces of experimentally infected rats. A
      mouse polyclonal IgG antibody against adult C. sinensis crude antigen (CsAg) was
      used to capture the C. sinensis coproantigen. The detection limit for pure CsAg
      was 20 ng/ml in sample buffer and 40 ng/ml in uninfected fecal extract. The test
      was evaluated using a follow-up of five groups of rats experimentally infected
      with 100, 50, 10, 5 and 1 metacercariae of C. sinensis and an uninfected control
      group. Coproantigen was detected in all infected groups of rats from 2 weeks of
      infection, whereas fecal eggs were not observed until 3 weeks of infection. As
      the infection period progressed, the fecal CsAg concentration increased in all
      groups of infected rats, even those infected with a single metacercaria. The
      fecal CsAg concentration was correlated positively with fecal egg counts and worm
      burden. This coproantigen capture ELISA is highly sensitive for the detection of
      CsAg in rat feces, and with further development, should be useful for mass
      screening of human subjects in clonorchiasis-endemic areas.

PMID- 21864713
TI  - The Synthesium Brachycladiidae Odhner, 1905 (Digenea) association with hosts
      based on nuclear and mitochondrial genes.
AB  - Synthesium pontoporiae, exclusive parasite of the endangered dolphin, Pontoporia
      blainvillei, is endemic and restricted to the South Atlantic and belongs to the
      Brachycladiidae family Odhner, 1905. The study of this family has been limited by
      the difficulty of accessing the parasites from their marine mammal hosts and as a
      consequence there is a paucity of genetic information available. Herein we
      present a genetic analysis using 18S rDNA sequences of S. pontoporiae and S.
      tursionis and the ND3 mtDNA sequence of S. pontoporiae. The genetic analysis of
      18S rDNA sequences of brachycladiids and acanthocolpids determined two major
      clusters associated with their definitive hosts, marine mammals and fishes,
      respectively. Considering the tree topology of brachycladiids ND3 mtDNA gene, two
      clusters were defined, one with the Synthesium species. This work contributes
      with fundamental genetic information on S. pontoporiae, and suggests a
      Brachycladiidae genetic evolution related to their hosts.

PMID- 21864715
TI  - Semantic integration of information about orthologs and diseases: the OGO system.
AB  - Semantic Web technologies like RDF and OWL are currently applied in life sciences
      to improve knowledge management by integrating disparate information. Many of the
      systems that perform such task, however, only offer a SPARQL query interface,
      which is difficult to use for life scientists. We present the OGO system, which
      consists of a knowledge base that integrates information of orthologous sequences
      and genetic diseases, providing an easy to use ontology-constrain driven query
      interface. Such interface allows the users to define SPARQL queries through a
      graphical process, therefore not requiring SPARQL expertise.

PMID- 21864716
TI  - Arterial remodeling and atherosclerosis: miRNAs involvement.
AB  - Cardiometabolic diseases (CMD) (such as atherosclerosis, diabetes, and
      hypertension) are the primary cause of death and disability in the Western world.
      Although lifestyle programs and therapeutic approaches have significantly reduced
      the socio-economic burden of CMD, a large number of events still cannot be
      avoided (the so called residual risk). Recent developments in genetics and
      genomics provide a platform for investigating further this area with the aim of
      deepening our understanding of the atherosclerotic phenomena underlying CMD, for
      instance by providing better information on the type of subjects who would
      benefit the most from therapeutic interventions, or by discovering new genetic
      and metabolic derangements that may be targeted for the development of new
      interventions. MicroRNAs (miRNA) are short, non-coding RNAs that negatively
      regulate the expression of proteins by binding to specific sequences on the 3'
      region of target mRNAs. Bioinformatics analysis predicts that each miRNA may
      regulate hundreds of targets, suggesting that miRNAs may play roles in almost
      every biological pathway and process, including those of the cardiovascular
      system. Studies are beginning to unravel their fundamental importance in vessel
      biology. Here, we review recent advance regarding the involvement of miRNAs in
      arterial remodeling and atherosclerosis.

PMID- 21864714
TI  - Anti-atherogenic mechanisms of high density lipoprotein: effects on myeloid
      cells.
AB  - In some settings increasing high density lipoprotein (HDL) levels has been
      associated with a reduction in experimental atherosclerosis. This has been most
      clearly seen in apolipoprotein A-I (apoA-I) transgenic mice or in animals infused
      with HDL or its apolipoproteins. A major mechanism by which these treatments are
      thought to delay progression or cause regression of atherosclerosis is by
      promoting efflux of cholesterol from macrophage foam cells. In addition, HDL has
      been described as having anti-inflammatory and other beneficial effects. Some
      recent research has linked anti-inflammatory effects to cholesterol efflux
      pathways but likely multiple mechanisms are involved. Macrophage cholesterol
      efflux may have a role in facilitating emigration of macrophages from lesions
      during regression. While macrophages can mediate cholesterol efflux by several
      pathways, studies in knockout mice or cells point to the importance of active
      efflux mediated by ATP binding cassette transporter (ABC) A1 and G1. In addition
      to traditional roles in macrophages, these transporters have been implicated in
      the control of hematopoietic stem cell proliferation, monocytosis and
      neutrophilia, as well as activation of monocytes and neutrophils. Thus, HDL and
      cholesterol efflux pathways may have important anti-atherogenic effects at all
      stages of the myeloid cell/monocyte/dendritic cell/macrophage lifecycle. This
      article is part of a Special Issue entitled Advances in High Density Lipoprotein
      Formation and Metabolism: A Tribute to John F. Oram (1945-2010).

PMID- 21864717
TI  - Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the
      rat.
AB  - The study has been designed to investigate the effect of fenofibrate on nicotine
      induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day,
      i.p., 4 weeks) was administered to produce VED in rats. The development of VED
      was assessed by employing isolated aortic ring preparation and estimating serum
      and aortic concentration of nitrite/nitrate. Further, the integrity of vascular
      endothelium was assessed using the scanning electron microscopy of thoracic
      aorta. The expression of mRNA for p22phox and eNOS was assessed by using reverse
      transcriptase-polymerase chain reaction. Serum thiobarbituric acid reactive
      substances concentration (TBARS) and aortic superoxide anion concentration were
      estimated to assess oxidative stress. Moreover, the serum lipid profile was
      assessed by estimating serum cholesterol, triglycerides and high density
      lipoprotein. The administration of nicotine induces VED by increased oxidative
      stress, altered lipid profile and impaired the integrity of vascular endothelium
      as assessed in terms of decrease in expression of mRNA for endothelial nitric
      oxide synthase (eNOS), impairing the integrity of vascular endothelium and
      subsequently decreasing serum and aortic nitrite/nitrate and attenuating
      acetylcholine-induced endothelium dependent relaxation. Further, nicotine
      produced oxidative stress, assessed in terms of increase in serum TBARS and
      aortic superoxide anion generation and increase in expression of mRNA for
      p22phox. Nicotine altered the lipid profile by increasing the serum cholesterol,
      triglycerides and decreasing the high density lipoprotein. However, treatment
      with fenofibrate (32 mg/kg, p.o.) markedly prevented nicotine-induced VED by
      decreasing oxidative stress and improving integrity of vascular endothelium,
      normalising the altered lipid profile, increasing the concentration of serum and
      aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent
      relaxation and decreasing serum TBARS and aortic superoxide anion generation.
      Thus, it may be concluded that fenofibrate has vascular protecting potential, by
      improving the integrity and function of vascular endothelium.

PMID- 21864718
TI  - A randomized trial of a diet and exercise intervention for overweight and obese
      women from economically disadvantaged neighborhoods: Sisters Taking Action for
      Real Success (STARS).
AB  - BACKGROUND: Lower socioeconomic status at both the individual and neighborhood
      level is associated with increased health risks. Weight loss can reduce this
      risk, but few high quality weight-loss studies target this population.
      OBJECTIVES: STARS tests a culturally appropriate, group-based behavioral and
      social support intervention on body weight and waist circumference in women from
      financially disadvantaged neighborhoods. DESIGN: A stratified (by BMI) randomized
      trial. Randomization to group was generated by a random numbers table with
      allocation concealment by opaque envelopes. METHODS: Participants 25-50 years who
      had a BMI >= 25 kg/m(2) and a waist circumference >= 88 cm were recruited from 18
      census tracts in Columbia, SC with high rates of poverty between November 2008
      and November 2010. All participants received a dietary and exercise counseling
      session. Intervention participants then receive 16 theoretically-based and
      tailored weekly group sessions followed by 8 weeks of telephone maintenance
      counseling. Control participants receive 16 weekly health education mailings.
      Measurements correspond to baseline, post-group intervention, and post-telephone
      counseling, and for intervention participants, after a 12-week no-contact period.
      Measurement staff was blinded to group assignment. RESULTS: Participants (N=155;
      n=80 intervention, n=75 minimal intervention control) were primarily African
      American (86.5%) and averaged 38.9 years with a mean BMI of 40.1 kg/m(2) and
      waist circumference of 115.4 cm. Food insecurity was reported by 43% of
      participants. SUMMARY: STARS targets an underserved population with an
      innovative, tailored, and theoretically-grounded, group-based intervention
      followed by telephone maintenance. If effective, the approach has the potential
      to be feasible and cost-effective for community delivery.

PMID- 21864719
TI  - Protocol for a randomised controlled trial of chronic disease self-management
      support for older Australians with multiple chronic diseases.
AB  - The prevalence of older Australians with multiple chronic diseases is increasing
      and now accounts for a large proportion of total health care utilisation. Chronic
      disease self-management support (CDSMS) has become a core service component of
      many community based health programs because it is considered a useful tool in
      improving population health outcomes and reducing the financial burden of chronic
      disease care. However, the evidence base to justify these support programs is
      limited, particularly for older people with multiple chronic diseases. We
      describe an ongoing trial examining the effectiveness of a particular CDSMS
      approach called the Flinders Program. The Flinders Program is a clinician-led
      generic self-management intervention that provides a set of tools and a
      structured process that enables health workers and patients to collaboratively
      assess self-management behaviours, identify problems, set goals, and develop
      individual care plans covering key self-care, medical, psychosocial and carer
      issues. A sample of 252 older Australians that have two or more chronic
      conditions will be randomly assigned to receive either CDSMS or an attention
      control intervention (health information only) for 6 months. Outcomes will be
      assessed using self-reported health measures taken at baseline and post
      intervention. This project will be the first comprehensive evaluation of CDSMS in
      this population. Findings are expected to guide consumers, clinicians and
      policymakers in the use of CDSMS, as well as facilitate prioritisation of public
      monies towards evidence-based services.

PMID- 21864720
TI  - Different name, same problems.

PMID- 21864721
TI  - Review of genetic diversity in malaria vectors (Culicidae: Anophelinae).
AB  - We review previous studies on the genetic diversity of malaria vectors to
      highlight the major trends in population structure and demographic history. In
      doing so, we outline key information about molecular markers, sampling strategies
      and approaches to investigate the causes of genetic structure in Anopheles
      mosquitoes. Restricted gene flow due to isolation by distance and physical
      barriers to dispersal may explain the spatial pattern of current genetic
      diversity in some Anopheles species. Nonetheless, there is noteworthy
      disagreement among studies, perhaps due to variation in sampling methodologies,
      choice of molecular markers, and/or analytical approaches. More refined
      genealogical methods of population analysis allowing for the inclusion of the
      temporal component of genetic diversity facilitated the evaluation of the
      contribution of historical demographic processes to genetic structure. A common
      pattern of past unstable demography (i.e., historical fluctuation in the
      effective population size) by several Anopheles species, regardless of
      methodology (DNA markers), mosquito ecology (anthropophilic vs zoophilic), vector
      status (primary vs secondary) and geographical distribution, suggests that
      Pleistocene environmental changes were major drivers of divergence at population
      and species levels worldwide.

PMID- 21864722
TI  - Vitamin D endocrine system involvement in autoimmune rheumatic diseases.
AB  - Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight
      and then metabolized into an active D hormone in liver, kidney and peripheral
      immune/inflammatory cells. These endocrine-immune effects include also the
      coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase
      (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in
      mediating intracrine and paracrine actions. Vitamin D is implicated in prevention
      and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast
      cancer) and autoimmune rheumatic diseases since regulates both innate and
      adaptive immunity potentiating the innate response (monocytes/macrophages with
      antimicrobial activity and antigen presentation), but suppressing the adaptive
      immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B
      lymphocytes and Ig production and recent reports have demonstrated that
      1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual
      rhythm of trough vitamin D levels in winter and peaks in summer time showed
      negative correlation with clinical status at least in rheumatoid arthritis and
      systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis
      during winter or spring have been associated with greater radiographic evidence
      of disease progression at 12 months possibly are also related to seasonal lower
      vitamin D serum levels.

PMID- 21864723
TI  - B cells are resistant to immunomodulation by 'IVIg-educated' dendritic cells.
AB  - Intravenous immunoglobulin (IVIg) can exert beneficial effects in autoimmune and
      inflammatory diseases via several mutually non-exclusive mechanisms. While, IVIg
      can directly modulate the functions of both innate and adaptive immune cells such
      as dendritic cells (DC), macrophages, B and T cells, several reports have also
      highlighted that the regulation of immune responses by IVIg can be indirect. In
      view of these results, we aimed at exploring whether indirect regulation of
      immune cells by 'IVIg-educated' innate cells is a universal phenomenon. We
      addressed this question by deciphering the modulation of B cell functions by
      'IVIg-educated' DC. Our results indicate that human B cells are resistant to
      immunomodulation by 'IVIg-educated' DC. However, IVIg at therapeutic
      concentrations can directly inhibit B cell activation and proliferation. These
      results thus suggest that, indirect modulation of immune cells by IVIg is not a
      universal phenomenon.

PMID- 21864724
TI  - Evolving paradigms in H+ control of breathing: from homeostatic regulation to
      homeostatic competition.

PMID- 21864725
TI  - Predictors of nocturnal oxyhemoglobin desaturation in COPD.
AB  - It would be useful to detect predictors of marked nocturnal oxyhemoglobin
      desaturation (NOD) among COPD patients, who do not have respiratory failure when
      awake and sleep apnea (SA). Stable COPD patients with awake Pa(O2) >= 60 mmHg and
      Pa(CO2) <= 45 mmHg underwent cardio-respiratory polysomnography to exclude SA and
      to assess NOD. The patients that spent more than 30% of night time with Sp(O2) <
      90%, were defined desaturators (D), and the others non desaturators (ND).
      Pulmonary function testing was performed to determine lung volumes, maximal flow
      rates, lung diffusion capacity for carbon monoxide and maximal inspiratory and
      expiratory pressure (P(Imax) and P(Emax)). Negative expiratory pressure test was
      performed to assess tidal expiratory flow limitation. Supine pharyngometry was
      performed to determine upper airway size, shuttle walking test to assess exercise
      desaturation. Twenty-one patients were included in the study (18 male, age 66.0+/
      7.2 years, Body Mass Index 25.9+/-4.4 kg/m(2), FEV(1) 47.2+/-16.4% pred., Pa(O2)
      74.7+/-6.9 mmHg, Pa(CO2) 40.3+/-3.4 mmHg): 10 were D and 11 ND. Significant
      differences between the two groups were found in diurnal Pa(CO2) (D: 42.4+/-3.0
      vs. ND: 38.3+/-2.6mmHg; p<0.01), diurnal Sp(O2) (D: 94.0+/-1.5 vs. ND: 95.9+/
      0.9%; p<0.01), inspiratory capacity (IC) (D: 69.6+/-11.9 vs. ND: 87.0+/-17.7%
      pred.; p<0.05), and oro-pharyngeal junction area (OPJ) (D: 0.8+/-0.2 vs. ND:
      1.2+/-0.3 cm(2); p<0.01). Among parameters related to marked NOD at the
      univariate analysis, [Formula: see text] and OPJ remained as independent
      predictors after stepwise multiple regression analysis. These findings indicate
      that previously unrecognized factors such as smaller upper airway caliber and
      lung dynamic hyperinflation are associated with marked NOD in stable COPD
      patients without daytime respiratory failure and SA.

PMID- 21864727
TI  - Calpains: an elaborate proteolytic system.
AB  - Calpain is an intracellular Ca(2+)-dependent cysteine protease (EC 3.4.22.17;
      Clan CA, family C02). Recent expansion of sequence data across the species
      definitively shows that calpain has been present throughout evolution; calpains
      are found in almost all eukaryotes and some bacteria, but not in archaebacteria.
      Fifteen genes within the human genome encode a calpain-like protease domain.
      Interestingly, some human calpains, particularly those with non-classical domain
      structures, are very similar to calpain homologs identified in evolutionarily
      distant organisms. Three-dimensional structural analyses have helped to identify
      calpain's unique mechanism of activation; the calpain protease domain comprises
      two core domains that fuse to form a functional protease only when bound to
      Ca(2+)via well-conserved amino acids. This finding highlights the mechanistic
      characteristics shared by the numerous calpain homologs, despite the fact that
      they have divergent domain structures. In other words, calpains function through
      the same mechanism but are regulated independently. This article reviews the
      recent progress in calpain research, focusing on those studies that have helped
      to elucidate its mechanism of action. This article is part of a Special Issue
      entitled: Proteolysis 50 years after the discovery of lysosome.

PMID- 21864726
TI  - Intraprotein electron transfer between the FMN and heme domains in endothelial
      nitric oxide synthase holoenzyme.
AB  - Intraprotein electron transfer (IET) from flavin mononucleotide (FMN) to heme is
      an essential step in nitric oxide (NO) synthesis by NO synthase (NOS). The IET
      kinetics in neuronal and inducible NOS (nNOS and iNOS) holoenzymes have been
      previously determined in our laboratories by laser flash photolysis [reviewed in:
      C.J. Feng, G. Tollin, Dalton Trans., (2009) 6692-6700]. Here we report the
      kinetics of the IET in a bovine endothelial NOS (eNOS) holoenzyme in the presence
      and absence of added calmodulin (CaM). The IET rate constant in the presence of
      CaM is estimated to be ~4.3s(-1). No IET was observed in the absence of CaM,
      indicating that CaM is the primary factor in controlling the FMN-heme IET in the
      eNOS enzyme. The IET rate constant value for the eNOS holoenzyme is approximately
      10 times smaller than those obtained for the iNOS and CaM-bound nNOS holoenzymes.
      Possible mechanisms underlying the difference in IET kinetics among the NOS
      isoforms are discussed. Because the rate-limiting step in the IET process in
      these enzymes is the conformational change from input state to output state, a
      slower conformational change (than in the other isoforms) is most likely to cause
      the slower IET in eNOS.

PMID- 21864728
TI  - Spherical indentation of free-standing acellular extracellular matrix membranes.
AB  - Numerous scaffold materials have been developed for tissue engineering and
      regenerative medicine applications to replace or repair damaged tissues and
      organs. Naturally occurring scaffold materials derived from acellular xenogeneic
      and autologous extracellular matrix (ECM) are currently in clinical use. These
      biological scaffold materials possess inherent variations in mechanical
      properties. Spherical indentation or ball burst testing has commonly been used to
      evaluate ECM and harvested tissue due to its ease of use and simulation of
      physiological biaxial loading, but has been limited by complex material
      deformation profiles. An analytical methodology has been developed and applied to
      experimental load-deflection data of a model hyperelastic material and
      lyophilized ECM scaffolds. An optimum rehydration protocol was developed based on
      water absorption, hydration relaxation and dynamic mechanical analysis. The
      analytical methodology was compared with finite element simulations of the tests
      and excellent correlation was seen between the computed biaxial stress resultants
      and geometry deformations. A minimum rehydration period of 5 min at 37 degrees C
      was sufficient for the evaluated multilaminated ECM materials. The proposed
      approach may be implemented for convenient comparative analysis of ECM materials
      and source tissues, process optimization or during lot release testing.

PMID- 21864729
TI  - Nitric oxide modulates metalloproteinase-2, collagen deposition and adhesion rate
      after polypropylene mesh implantation in the intra-abdominal wall.
AB  - Prosthetic meshes are commonly used to correct abdominal wall defects. However,
      the inflammatory reaction induced by these devices in the peritoneum is not
      completely understood. We hypothesized that nitric oxide (NO), produced by nitric
      oxide synthase 2 (NOS2) may modulate the response induced by mesh implants in the
      abdominal wall and, consequently, affect the outcome of the surgical procedure.
      Polypropylene meshes were implanted in the peritoneal side of the abdominal wall
      in wild-type and NOS2-deficient (NOS2(-/-)) mice. After 15 days tissues around
      the mesh implant were collected, and inflammatory markers (the cytokine
      interleukin 1beta (IL-1beta) and NO) and tissue remodeling (collagen and
      metalloproteinases (MMP) 2 and 9) were analyzed. The lack of NOS2-derived NO
      induced a higher incidence of visceral adhesions at the mesh implantation site
      compared with wild-type mice that underwent the same procedure (P<0.05).
      Additionally, higher levels of IL-1beta were present in the mesh-implanted NOS2(
      /-) animals compared with control and wild-type mice. Mesh implantation induced
      collagen I and III deposition, but in smaller amounts in NOS2(-/-) mice. MMP-9
      activity after the surgical procedure was similarly increased in both groups.
      Conversely, MMP-2 activity was unchanged in mesh-implanted wild-type mice, but
      was significantly increased in NOS2(-/-) mice (P<0.01), due to decreased S
      nitrosylation of the enzyme in these animals. We conclude that NOS2-derived NO is
      crucial for an adequate response to and integration of polypropylene mesh
      implants in the peritoneum. NO deficiency results in a prolonged inflammatory
      reaction to the mesh implant, and reduced collagen deposition may contribute to
      an increased incidence of visceral adhesions.

PMID- 21864730
TI  - Inkjet printed antibiotic- and calcium-eluting bioresorbable nanocomposite
      micropatterns for orthopedic implants.
AB  - Inkjet printing of antibiotic- and calcium-eluting micropatterns was explored as
      a novel means of preventing the formation of biofilm colonies and facilitating
      osteogenic cell development on orthopedic implant surfaces. The micropatterns
      consisted of a periodic array of ~50 MUm circular dots separated by ~150 MUm. The
      composition of the micropatterns was controlled by formulating inks with
      rifampicin (RFP) and poly(D,L-lactic-co-glycolic) acid (PLGA) dissolved in an
      organic solvent with ~100 nm biphasic calcium phosphate (BCP) nanoparticles
      suspended in the solution. During printing RFP and PLGA co-precipitated to form a
      nanocomposite structure with ~10-100 nm RFP and the BCP particles dispersed in
      the PLGA matrix. The rate of RFP release was strongly influenced by the RFP
      loading in the micropattern, particularly on the first day. The RFP-containing
      micropatterns effectively prevented the formation of Staphylococcus epidermidis
      biofilm colonies due to their ability to kill bacteria prior to forming colonies
      on the patterned surfaces. The BCP-containing micropatterns printed on the
      surface of the alloy TiAl6V4 significantly accelerated osteoblast cell
      differentiation, as measured by alkaline phosphatase expression and calcium
      deposition, without compromising cell proliferation.

PMID- 21864731
TI  - Proteomic analysis of 1alpha,25-dihydroxyvitamin D3 action on human colon cancer
      cells reveals a link to splicing regulation.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and other vitamin D compounds
      are promising molecules in the prevention and therapy of colon cancer and other
      neoplasias. To study the mechanism of action of 1,25(OH)(2)D(3) in colon cancer
      cells, we carried out a comparative proteomic analysis of the nuclear fractions
      of SW480-ADH cells treated with 1,25(OH)(2)D(3) or vehicle during 8 or 48h. 2D
      DIGE analysis combined with MALDI-TOF-TOF mass spectrometry interrogation led to
      the identification of 59 differentially expressed unique proteins. Most
      identified proteins were nuclear, but several cytoskeleton-associated proteins
      were also detected. A good concordance between changes in expression at protein
      and RNA levels was observed for the validated proteins. A large group of
      identified proteins, such as SFPQ, SMARCE, KHSRP, TARDBP and PARP1, were involved
      in RNA processing or modification and have been ascribed to the spliceosome
      compartment of human cells. In addition, a smaller group of proteins (ERM (Ezrin,
      Radixin, Moesin) family, VCL, CORO1C, ACTB) were cytoskeleton-associated and
      played a role in cell adhesion and morphology. These results confirm the
      induction of epithelial phenotype by 1,25(OH)(2)D(3) and suggest a role for
      vitamin D compounds in the regulation of the spliceosome and thus, in alternative
      splicing and possibly microRNA synthesis in colon cancer cells.

PMID- 21864732
TI  - Association between sleep duration and bone mineral density in Chinese women.
AB  - BACKGROUND: Short sleep duration has been found to be closely related to several
      endocrine and metabolic dysfunctions. However, evidence of the association
      between insufficient sleep and bone health was limited. OBJECTIVE: The present
      study was aimed to examine the relationships between sleep duration and bone
      mineral density (BMD) in Chinese women. METHODS: Six hundred and two women aged
      18-80 years were analyzed. Sleep duration was collapsed to form categories of 5h
      or less, 6h, 7h, 8h, and 9h or more. Total and regional BMD were measured using
      dual-energy X-ray absorptiometry. Multiple regression analysis was performed to
      examine the relationships between sleep duration categories and BMD. RESULTS:
      Women with a short sleeping duration were more likely to have lower total and all
      body regional BMD after adjusting for potential covariates (all p values for
      trend <0.05). Compared to those who slept 8h, individuals who slept 5h or less
      and 6h had significant lower total and regional BMD (beta coefficients ranged 
      0.07 to -0.11, all p<0.05). When further divided women into 18-44 years old and
      45 years or older groups, and reran the regression models, the significant
      associations between BMD and sleep duration were only observed in 45 years or
      older group. CONCLUSIONS: Significant variations in total and regional BMD with
      sleep duration were observed in women. Decreased sleep duration closely
      associated with lower BMD, especially in middle-age and elderly women. These
      findings may lead to the development of better preventive approaches to
      osteoporosis in women through identification of potential modifiable risk
      factors.

PMID- 21864733
TI  - Common and rare variants in alcohol dependence.

PMID- 21864734
TI  - New approaches to identifying rare genetic variants associated with nicotine
      dependence.

PMID- 21864735
TI  - Functions of arginine vasopressin and its receptors: importance of human
      molecular genetics studies in bidirectional translational research.

PMID- 21864736
TI  - Paths of discovery in motoneuron neurobiology.

PMID- 21864737
TI  - [The Board of Directors of the Societe de stomatologie et de chirurgie maxillo
      faciale].

PMID- 21864738
TI  - Combinations of insulin and oral hypoglycemic agents in diabetes mellitus type 2.
AB  - Insulin therapy is considered to be the most effective therapy for the reduction
      of high glucose levels. In patients who cannot be regulated with the combination
      of oral hypoglycemic agents, insulin should be administrated. The first step is
      the combination of insulin together with the already administrated oral
      hypoglycemic agents. The fear for hypoglycemia, the refusal and weakness that
      patients face when dealing with insulin, constitute reasons for many doctors to
      deal with insulin therapy in a more skeptical way. As a result, the initiation of
      insulin therapy is delayed for those patients who need it for hyperglycemia
      adjustments. This article provides useful practical instructions for initiating
      insulin therapy.

PMID- 21864739
TI  - Insulin analogs versus human insulin in type 2 diabetes.
AB  - Oral hypoglycaemic agents become less effective as beta cell function declines.
      Thus many patients with type 2 diabetes will ultimately require treatment with
      insulin. There are two main approaches to starting insulin: (a) as a basal
      supplement with an intermediate to long-acting preparation (NPH, glargine or
      detemir) plus oral agents; (b) as a premixed insulin regimen. Almost all the
      studies have shown similar glucose control with both NPH and the new insulin
      analogs. Further analyses between these insulins have documented significant
      reductions in hypoglycaemia especially at night with the insulin analogs. The
      weight gain is an important issue in patients with diabetes. It appears that
      insulin detemir studies have reported weight neutrality or less weigh gain or
      even weight loss. However, most insulin glargine studies have reported a weight
      gain. On the other hand insulin analogs have the important disadvantage of high
      cost. It is important to take in to account all the above factors such as cost,
      weight gain, number of insulin injections and hypoglycaemia while prescribing
      insulin.

PMID- 21864740
TI  - Antiatheromatic effects of insulin.
AB  - Despite numerous publications according to which insulin promotes
      atherosclerosis, there are many observations in the last fifteen years suggesting
      that insulin has antiatherogenic properties. Insulin has vasodilatory,
      antithrombotic and anti-inflammatory effects. A good glycemic control contributes
      to the maximum efficiency of antiatherogenic action of insulin. Insulin
      resistance promotes the atherosclerotic process because of diminished insulin
      action and not because of hyperinsulinemia, since insulin secretion is getting
      lower during the years in type 2 diabetes.

PMID- 21864741
TI  - Insulin pump therapy in adults.
AB  - Restoration of the physiological insulin secretion is a current medical challenge
      and a dream for patients with Diabetes Mellitus. Continuous insulin therapy using
      pumps was the first step to the development of artificial pancreas. The aim of
      diabetes treatment is to achieve strict glycemic control in order to avoid the
      development of long-term diabetic complications while reducing the frequency of
      hypoglycemic episodes. Continuous subcutaneous insulin infusion (CSII) using an
      external pump, offers both a better blood glucose stability as compared to
      multiple daily injections and a broader flexibility in life mode, and reduces the
      frequency of severe hypoglycemia. The advantages of the insulin pump (consistency
      of basal delivery, adjustable basal rates, and low insulin depots allowing the
      reduction of glycemic variability) have contributed to its reported superiority
      compared with multiple daily injections (MDI). However, experience with CSII
      indicates that candidates for insulin pump therapy must be carefully selected and
      strongly motivated to improve their glucose control. Finally, the use of CSII in
      patients with Diabetes Mellitus type 2 now appears to be a good alternative to
      the ineffective MDI regimens observed in some of these patients.

PMID- 21864742
TI  - Insulin therapy in children and adolescents with diabetes.
AB  - Diabetes type 1 constitutes a growing problem for many children and adolescents
      worldwide. Diabetic children and adolescents are dependent on insulin for
      survival. Today, insulin treatment, either in the classic insulin forms or in the
      form of insulin analogs, is widely used in the pediatric diabetic population. New
      methods of insulin administration like the continuous subcutaneous insulin
      infusion systems (pumps) have been developed to ameliorate metabolic control and
      reduce diabetic complications.

PMID- 21864743
TI  - Treatment of type 1 diabetes in children and adolescents using modern insulin
      pumps.
AB  - In the last decades, we are experiencing an increasing use of insulin pumps for
      the treatment of type 1 diabetes in children and adolescents. The most frequent
      reasons for switching from insulin injection schemes to pump therapy are frequent
      and/or severe hypoglycaemia, dawn phenomenon, poor glycaemic control, wish for
      more flexibility in daily life, and needle phobia. In toddlers and preschoolers,
      pumps are frequently introduced from the onset of type 1 diabetes. Pumps offer
      the possibility of adjusting basal insulin rates individually on an age-depended
      manner as well as of optimizing meal-related insulin requirements according to
      the meal composition by using three different kinds of boluses. Structured and
      intensive education of patients and their families on basics and specific
      requirements of insulin pump therapy is essential in order to get them familiar
      with the devices and their features. There is increasing evidence both from
      multicentre cross-sectional studies as well as from meta-analyses of randomized
      clinical trials in paediatric populations showing that patients with pump therapy
      can achieve a more favourable metabolic control accompanied with less
      hypoglycaemic events than those with multiple daily injections.

PMID- 21864744
TI  - Continuous blood glucose monitoring in diabetes treatment.
AB  - Continuous glucose monitoring system (CGMS) is a developing technology in the
      field of diabetes treatment since it enables patients to effectively control and
      adjust their insulin therapy. Clinical trials have shown its efficacy in lowering
      HbAlc significantly especially in adults with type 1 diabetes and those with
      HbAlc >8%. Improvement is sustained for at least one year. Conflicting data exist
      for children. Most recent studies agree that the nearly daily use of CGMS is
      accompanied by significant lowering of HbA1c independent of age. However, the
      randomized clinical trials have shown that the use of CGMS does not reduce
      significantly the number of severe hypoglycemic episodes as it is expected, but
      recent data indicate that it reduces the time spent in hypoglycemia. Accuracy
      remains a key issue for CGMS, particularly in children and adolescents who may
      have increased variability of blood glucose. CGMS cost is another barrier to the
      everyday use since reimbursement of CGM is limited to a few countries only. This
      review will focus on the present status of the use of CGMS in type 1 diabetes
      (T1D) patients.

PMID- 21864745
TI  - Closed-loop in children with type 1 diabetes: specific challenges.
AB  - OBJECTIVE: To review challenges and opportunities related to closed-loop glucose
      control in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS:
      During closed-loop glucose control, insulin infusion rates on a subcutaneous
      insulin pump are adjusted by a control algorithm according to subcutaneous
      glucose sensor readings. A literature review is performed and personal experience
      of work with closed-loop systems at the University of Cambridge, UK, is
      presented. RESULTS: The main challenges in the management of T1D in children are
      identified together with a summary of current therapeutics options. Review of the
      literature recognises hypoglycaemia as a limiting factor for the attainment of
      optimal glycaemic control, primarily in children. Additional specific confounding
      issues include unpredictable eating and exercise patterns especially in the
      youngest age group. Closed-loop systems might be particularly helpful, but have
      to consider increased insulin sensitivity, lower insulin doses, and human factors
      such as size and usability of closed-loop components. CONCLUSIONS: Closed-loop
      systems may represent an alternative treatment option to achieve target glucose
      levels whilst reducing the risk of hypoglycaemia in children with T1D.

PMID- 21864746
TI  - The story of insulin discovery.
AB  - Many researchers had tried to isolate insulin from animal pancreas, but Frederick
      Banting, a young surgeon, and Charles Best, a medical student, were the ones that
      succeeded. They both worked hard in very difficult conditions in the late 1921
      and early 1922 until final success. They encountered problems with the impurities
      of their extract that was causing inflammations, but J. Collip, their late
      biochemist collaborator, worked many hours and was soon able to prepare cleaner
      insulin, free from impurities. This extract was administered successfully to L.
      Thomson, a ketotic young diabetic patient, on 23 January 1922. Following this,
      Eli Lilly & Co of USA started the commercial production of insulin, soon followed
      by the Danish factories Nordisc and NOVO as well as the British Wellcome. Nicolae
      Paulescu who was professor of Physiology in Bucharest, was also quite close to
      the discovery of insulin but the researchers in Toronto were faster and more
      efficient. Banting and Macleod won the Nobel price, which Banting shared with
      Best and Macleod with J. Collip. The contribution of Paulescu in insulin
      discovery was recognized after his death.

PMID- 21864747
TI  - The role of alpha-, delta- and F cells in insulin secretion and action.
AB  - Nowadays, most of the basic pancreatic islet research is focused on the beta and
      alpha cells. Nonetheless, the pancreatic islets are complete organs with five, up
      to now, different cell types and dedicated vasculature and neural supply. Every
      cell contributes in the integration of the islet function and deserves a closer
      lookup in the saga of the glucose homeostasis. In this brief report we describe
      the current concepts about the contribution of the non-beta cells in the overall
      islet contribution to glucose metabolism.

PMID- 21864748
TI  - The dual control of insulin secretion by glucose involves triggering and
      amplifying pathways in beta-cells.
AB  - This review outlines the two pathways that interact in beta-cells to ensure
      temporal and amplitude control of insulin secretion by glucose. The most well
      known triggering pathway involves the following steps: acceleration of glucose
      metabolism, closure of ATP-sensitive potassium channels, depolarization, influx
      of Ca(2+) through voltage-gated calcium channels, and a rise in the concentration
      of cytosolic ionized Ca(2+) that triggers exocytosis of insulin-containing
      granules. This classic sequence is, however, incomplete. Additional mechanisms,
      involving other channels, are necessarily implicated in the production of the
      triggering Ca(2+) signal. It is also clear that the effect of glucose on insulin
      secretion would be poor if Ca(2+)-induced exocytosis was not markedly augmented
      (approximately doubled) through a metabolic amplifying pathway, mechanistically
      distinct from neurohormonal amplifying pathways. This metabolic amplifying
      pathway is physiologically relevant for both phases of glucose-induced insulin
      secretion and for the potentiation, by glucose, of insulin secretion triggered by
      non-metabolized secretagogues (e.g. arginine). Three important challenges for
      future studies will be to identify the additional targets mediating control of
      the triggering Ca(2+) signal by glucose, to elucidate the cellular mechanisms of
      the metabolic amplifying pathway and to determine the contribution of each
      pathway in the alterations of insulin secretion in type 2 diabetic patients.

PMID- 21864749
TI  - Incretin effect: GLP-1, GIP, DPP4.
AB  - The term incretin effect was used to describe the fact that oral glucose load
      produces a greater insulin response than that of an isoglycemic intravenous
      glucose infusion. This difference has been attributed to gastrointestinal
      peptides GLP-1 and GIP. Since incretin effect is reduced in subjects with type 2
      diabetes, despite GLP-1 activity preservation, two forms of incretin-based
      treatment have emerged: GLP-1R agonists, administered subcutaneously and DPP-4
      inhibitors, administered orally. There is a great interest whether incretin-based
      treatment will be associated with sustained long-term control and improvement in
      beta-cell function. The observation that GLP-1R agonists improve myocardial
      function and survival of cardiomyocytes highlights the need for further studies.
      Incretin-based therapies offer a new option and show great promise for the
      treatment of type 2 diabetes.

PMID- 21864750
TI  - Glucolipotoxicity and beta cells in type 2 diabetes mellitus: target for durable
      therapy?
AB  - Type 2 diabetes mellitus (T2DM) is characterised by beta-cell failure in the
      setting of obesity-related insulin resistance. Progressive beta-cell dysfunction
      determines the course of the disease, regardless of the treatment used. There is
      mounting evidence that chronically elevated circulating levels of glucose and
      fatty acids contribute to relentless beta-cell function decline, by endorsing
      processes commonly referred to as glucolipotoxicity. Mechanisms related to
      glucolipotoxicity include endoplasmic reticulum (ER) stress, oxidative stress,
      mitochondrial dysfunction and islet inflammation. The most commonly prescribed
      blood-glucose lowering agents, metformin and sul-fonylurea, may temporarily
      improve glycaemic control, however, these drugs do not alter the continuous
      decline in beta-cell function in T2DM patients. Evidence exists that novel
      classes of drugs, the thiazolidinediones (TZDs) and incretin-based therapies, may
      be able to preserve beta-cell function and functional beta-cell mass, amongst
      others by reducing glucolipotoxicity in the beta cell. The durability of the
      effects of TZDs and incretin-based therapies on beta-cell function, whether given
      as monotherapy or combined with other treatment, should be addressed in future,
      long-term clinical studies.

PMID- 21864751
TI  - Insulin sensitivity of the human brain.
AB  - The brain is an insulin sensitive organ and insulin signaling is important to
      regulate feeding behavior, body weight, and cognitive processes. Insulin
      resistance in peripheral tissues is a hallmark in the development of type 2
      diabetes mellitus (T2DM), yet the finding of insulin resistance in the brain is
      relatively novel. Studies in humans revealed that environmental factors like
      obesity, age, and the genetic background have an impact on central insulin
      sensitivity. According to the physiological effects of insulin in the brain,
      disturbances of this signaling chain lead to an impairment of cognitive functions
      and a deterioration of eating behavior with a potential role in the pathogenesis
      of obesity and T2DM. First attempts to treat insulin resistance not only in
      peripheral tissues but also in the CNS have therefore come on its way: Cerebral
      insulin resistance can at least partially be overcome by intranasal treatment
      with insulin or by commercial insulins that exhibit specific effects in the brain
      due to their pharmacokinetic properties. Despite the advances towards a better
      understanding of insulin function in the human brain in the last years, achieving
      a more profound knowledge of mechanisms behind central insulin function and
      identifying further strategies to overcome insulin resistance must be a main goal
      of future research.

PMID- 21864752
TI  - Insulin effects in muscle and adipose tissue.
AB  - The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate
      metabolism: (a) it increases the rate of glucose transport across the cell
      membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6
      phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis
      and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it
      decreases the rate of lipolysis in adipose tissue and hence lowers the plasma
      fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in
      tissues, (c) it increases the uptake of triglycerides from the blood into adipose
      tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle
      and liver. (3) Protein metabolism: (a) it increases the rate of transport of some
      amino acids into tissues, (b) it increases the rate of protein synthesis in
      muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of
      protein degradation in muscle (and perhaps other tissues). These insulin effects
      serve to encourage the synthesis of carbohydrate, fat and protein, therefore,
      insulin can be considered to be an anabolic hormone.

PMID- 21864753
TI  - Role of beta-cell dysfunction, ectopic fat accumulation and insulin resistance in
      the pathogenesis of type 2 diabetes mellitus.
AB  - In the natural history of type 2 diabetes (T2DM), individuals progress from
      normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to overt T2DM
      and this progression has been demonstrated in populations of diverse ethnic
      background. It is widely recognised that both insulin resistance and beta-cell
      dysfunction are important in the pathogenesis of glucose intolerance. In
      populations with a high prevalence of T2DM, insulin resistance is well
      established long before the development of any impairment in glucose homeostasis,
      particularly in subjects with ectopic fat accumulation. However, as long as the
      beta cell is able to secrete sufficient amounts of insulin to offset the severity
      of insulin resistance, glucose tolerance remains normal. This dynamic interaction
      between insulin secretion and insulin resistance is essential to the maintenance
      of NGT and interruption of this crosstalk between the beta cell and peripheral
      tissues results in the progressive deterioration of glucose homeostasis. In this
      paper the role of beta-cell function is reviewed, as well as the role of ectopic
      fat accumulation and insulin resistance in the development of type 2 diabetes.

PMID- 21864754
TI  - Kidney: its impact on glucose homeostasis and hormonal regulation.
AB  - According to current textbook wisdom the liver is the exclusive site of glucose
      production in humans in the postabsorptive state. Although animal and in vitro
      studies have documented that the kidney is capable of gluconeogenesis, glucose
      production by the human kidney has been regarded as negligible. This knowledge is
      based on net balance measurements across the kidney. Recent studies combining
      isotopic and balance techniques have demonstrated that the human kidney is
      involved in the regulation of glucose homeostasis by making glucose via
      gluconeogenesis, taking up glucose from the circulation, and by reabsorbing
      glucose from the glomerular filtrate. The human liver and kidneys release
      approximately equal amounts of glucose via gluconeogenesis in the postabsorptive
      state. In the postprandial state, although overall endogenous glucose release
      decreases substantially, renal gluconeogenesis actually increases by
      approximately 2-fold. Following meal ingestion, glucose utilization by the kidney
      increases. Increased glucose uptake into the kidney may be implicated in diabetic
      nephropathy. Normally each day, ~ 180 g of glucose is filtered by the kidneys;
      almost all of this is reabsorbed by means of sodium glucose cotransporter 2
      (SGLT2), expressed in the proximal tubules. However, the capacity of SGLT2 to
      reabsorb glucose from the renal tubules is finite and when plasma glucose
      concentrations exceed a threshold, glucose begins to appear in the urine. Renal
      glucose release is stimulated by epinephrine and is inhibited by insulin.
      Handling of glucose by the kidney is altered in type 2 diabetes mellitus (T2DM):
      renal gluconeogenesis and renal glucose uptake are increased in both the
      postabsorptive and postprandial states, and renal glucose reabsorption is also
      increased Since renal glucose release is almost exclusively due to
      gluconeogenesis, it seems that the kidney is as important gluconeogenic organ as
      the liver. The most important renal gluconeogenic precursors appear to be lactae
      glutamine and glycerol.

PMID- 21864755
TI  - Insulin therapy and exercise.
AB  - Medical nutrition therapy and physical exercise are the cornerstones of the
      diabetes management. Patients with type 1 DM always need exogenous insulin
      administration, recently available in the form of insulin analogs. In type 2 DM,
      characterized by increased insulin resistance and progressive decline of the beta
      cell function, various antidiabetic medications are used. Most of the subjects
      with type 2 DM will finally need insulin. The main site of insulin action is the
      skeletal muscle, while the liver is the main site of glucose storage in the form
      of glycogen. With the modern diabetes therapies it is possible to rapidly reach
      and maintain normoglycemia in both types of DM but with the cost of higher
      incidence of hypoglycemia, especially related to exercise. Regular physical
      exercise causes a lot of beneficial effects in healthy as well as diabetic
      subjects of all age groups. In type 1 DM physical exercise is a fundamental
      element for both physical and mental development. In type 2 DM it has a main role
      in diabetes control. The increased hepatic glucose production and the increased
      muscular glucose uptake during exercise are closely interrelated in all exercise
      intensities. In diabetes mellitus there is a disturbed energy substrate use
      during exercise leading to either hypo- or hyperglycemia. The influence of low or
      moderate intensity aerobic exercise on diabetes control has been well studied.
      The inappropriately high insulinemia combined with the low glucose levels can
      lead to severe hypoglycemia if proper measures are not taken. Prolonged exercise
      can also predispose to decreased glucose counter regulation. It is better for the
      type 1 diabetic subject to postpone the exercise session in very high (>300
      mg/dl) or very low (<70 mg/dl) BG levels. Every insulin treated subject is
      recommended to be checked for any existing diabetic complication before the start
      of every exercise program. Glucose measurement with glucose meters or sometimes
      with Continuous Glucose Monitoring System (CGMS) must be made before, during and
      most importantly after the end of the exercise session. It is recommended either
      to reduce or suspend the previous insulin dose depending on the insulin regime or
      to receive extra carbohydrates before, during or after the exercise session or
      both. Subjects with type 1 DM may participate at almost all the competitive
      sports if precautions are taken. These measures must be individualized and
      readjusted, even empirically. In very high intensity exercise (about 80% of VO(2
      max)) or when high intensity exercise follows a low intensity one, there is a
      tendency of the BG to increase due to excessive circulating catecholamines
      necessitating postexercise short acting insulin. In anaerobic or resistance
      exercise lactic acid is produced. This exercise type is recommended for people in
      whom aerobic exercise is contraindicated. These two exercise types can be
      combined. The incidence of hypoglycemia or hyperglycemia in specific forms of
      resistance exercise as well as the appropriate insulin dose adjustment are not
      well studied. In conclusion all exercise types are beneficial for both types of
      diabetes.

PMID- 21864756
TI  - Insulin therapy during hospitalization.
AB  - Hyperglycemia occurring during hospitalization is a common phenomenon among
      patients with or without a known history of diabetes mellitus. For several years,
      hyperglycemia in hospitalized patients had been considered as an accompanying
      characteristic of the acute disease that resulted in admission. That point of
      view changed over time mainly because of emerging indications from clinical
      studies showing that hyperglycemia during hospitalization could aggravate
      prognosis and increase mortality. Further studies engaged on how hyperglycemia
      should be treated, yielded results that highlighted the increasing risk of
      mortality due to hypoglycemia in such efforts and also questioned the initial
      relation between hyperglycemia during hospitalization and a poor prognosis. Based
      on the fact that there is still no common ground on what is the best approach on
      hyperglycemia of hospitalized patients, the best practice remains to follow a
      different regime with different glycemic goals for different patient groups. In
      this review, hospitalized patients are divided into three groups; intensive care
      unit patients (general and cardiac), non-intensive care unit patients (general
      and cardiac) and peri-operative patients.

PMID- 21864757
TI  - Insulin and the heart.
AB  - The main role of insulin in the heart under physiological conditions is obviously
      the regulation of substrate utilization. Indeed, insulin promotes glucose uptake
      and its utilization via glycolysis. Insulin, promoting glucose as the main
      cardiac energy substrate, reduces myocardial O(2) consumption and increases
      cardiac efficiency. Moreover, insulin seems to augment cardiomyocyte contraction,
      while it affects favorably myocardial relaxation, increases ribosomal biogenesis
      and protein synthesis, stimulates vascular endothelial growth factor (VEGF) and
      thereby angiogenesis, suppresses apoptosis, promotes cell survival and finally
      ameliorates both myocardial microcirculation and coronary artery resistance,
      leading to increased blood perfusion of myocardium. Thus, insulin acts directly
      on heart muscle, and this action is mediated principally through PKB/Akt signal
      pathway. Under pathological conditions, such as type 2 diabetes, myocardial
      ischaemia, and cardiac hypertrophy, insulin signal transduction pathways and
      action are clearly modified. In this review we summarize the evidence that the
      heart is an important target of insulin action and that elimination of these
      actions is important in disease states.

PMID- 21864759
TI  - Hypoglycemia unawareness.
AB  - Iatrogenic hypoglycemia is the limiting factor in the glycemic control of
      diabetes. It causes recurrent symptomatic and sometimes, at least temporally,
      disabling episodes in most people with type 1 diabetes, as well as in many with
      advanced type 2 diabetes. Furthermore, iatrogenic hypoglycemia precludes
      maintenance of euglycemia during the lifetime of a person with diabetes and thus
      full realization of the well established benefits of glycemic control. In this
      article I discuss the clinical problem of hypoglycemia in diabetes from the
      perspective of pathophysiology. First, the syndromes of defective glucose
      counterregulation and hypoglycemia without warning symptoms (known as
      hypoglycemia unawareness) are described, followed by the unifying concept of
      Hypoglycemia-Associated Autonomie Failure (HAAF). The concept of hypoglycemia
      associated autonomie failure in diabetes posits that recurrent antecedent
      hypoglycemia causes both defective glucose counterregulation and hypoglycemia
      unawareness and thus leads to a vicious cycle of recurrent hypoglycemia and
      further impairment of glucose counterregulation. The clinical relevance of this
      phenomenon is now well established, but the mechanisms and mediators remain
      largely unknown. The short-term avoidance of hypoglycemia reverses hypoglycemia
      unawareness in most affected patients. The ultimate goal of lifelong maintenance
      of euglycemia in patients with diabetes remains elusive because of the
      pharmacokinetic imperfections of all current glucose-lowering therapies and the
      resulting barrier of hypoglycemia. Nonetheless, it is now possible both to
      improve the control of glycemia and to reduce the frequency of hypoglycemia in
      many people with diabetes. These results can be accomplished by recognizing the
      problem of hypoglycemia applying the principles of aggressive glycemic therapy
      and reducing the risk factors of hypoglycemia in people with diabetes.

PMID- 21864758
TI  - New type 2 diabetes risk genes provide new insights in insulin secretion
      mechanisms.
AB  - Type 2 diabetes results from the inability of beta cells to increase insulin
      secretion sufficiently to compensate for insulin resistance. Insulin resistance
      is thought to result mainly from environmental factors, such as obesity. However,
      there is compelling evidence that the decline of both insulin sensitivity and
      insulin secretion have also a genetic component. Recent genome-wide association
      studies identified several novel risk genes for type 2 diabetes. The vast
      majority of these genes affect beta cell function by molecular mechanisms that
      remain unknown in detail. Nevertheless, we and others could show that a group of
      genes affect glucose-stimulated insulin secretion, a group incretin-stimulated
      insulin secretion (incretin sensitivity or secretion) and a group proinsulin-to
      insulin conversion. The most important so far type 2 diabetes risk gene, TCF7L2,
      interferes with all three mechanisms. In addition to advancing knowledge in the
      pathophysiology of type 2 diabetes, the discovery of novel genetic determinants
      of diabetes susceptibility may help understanding of gene-environment, gene
      therapy and gene-gene interactions. It was also hoped that it could make
      determination of the individual risk for type 2 diabetes feasible. However, the
      allelic relative risks of most genetic variants discovered so far are relatively
      low. Thus, at present, clinical criteria assess the risk for type 2 diabetes with
      greater sensitivity and specificity than the combination of all known genetic
      variants.

PMID- 21864760
TI  - Fear, guilt feelings and misconceptions: barriers to effective insulin treatment
      in type 2 diabetes.
AB  - Diabetes self management education, the process of teaching individuals to manage
      their diabetes, has been considered the cornerstone of the clinical management of
      individuals with diabetes since the work of the Joslin Diabetes Center. The goals
      of self-management education are to optimize metabolic control, prevent acute and
      chronic complications, and optimize quality of life. The keystone to successful
      management is to involve the patient in his treatment. Clearly, factors other
      than knowledge and effective therapies affect the behaviors of patients and
      health care professionals and influence their ability to make optimal use of
      available treatments. The DAWN study has shown that both health care providers
      and patients may have a negative attitude toward starting insulin therapy.
      Patients with type 2 diabetes are very often reluctant to accept insulin therapy.
      The reasons most commonly encountered, for this negative attitude are: Patients
      blame themselves, for they consider that starting insulin therapy would indicate
      they had "failed" proper diabetes self-management. For some patients taking
      insulin means life will be more restricted or it means they have reached their
      last resort. Fear of hypoglycemia is a very common barrier for insulin therapy.
      Physicians may, unconsciously, negatively influence their patients. For some
      physicians putting his patient on insulin, means that he has failed to control
      his patient's diabetes on oral agents and now has to force him in a troublesome
      therapeutic regime. In order to overcome these barriers, health care
      professionals, rather than trying to "convince" their patients of the necessity
      of the treatment, should assess, by active listening, the precise reason for
      which his/her patient denies it.

PMID- 21864762
TI  - Nursing and physician attire as possible source of nosocomial infections.
AB  - BACKGROUND: Uniforms worn by medical and nursing staff are not usually considered
      important in the transmission of microorganisms. We investigated the rate of
      potentially pathogenic bacteria present on uniforms worn by hospital staff, as
      well as the bacterial load of these microorganisms. METHODS: Cultures were
      obtained from uniforms of nurses and physicians by pressing standard blood agar
      plates at the abdominal zone, sleeve ends, and pockets. Each participant
      completed a questionnaire. RESULTS: A total of 238 samples were collected from
      135 personnel, including 75 nurses (55%) and 60 physicians (45%). Of these, 79
      (58%) claimed to change their uniform every day, and 104 (77%) defined the level
      of hygiene of their attire as fair to excellent. Potentially pathogenic bacteria
      were isolated from at least one site of the uniforms of 85 participants (63%) and
      were isolated from 119 samples (50%); 21 (14%) of the samples from nurses' gowns
      and 6 (6%) of the samples from physicians' gowns (P = NS) included of antibiotic
      resistant bacteria. CONCLUSION: Up to 60% of hospital staff's uniforms are
      colonized with potentially pathogenic bacteria, including drug-resistant
      organisms. It remains to be determined whether these bacteria can be transferred
      to patients and cause clinically relevant infection.

PMID- 21864764
TI  - Electron tomography combining ESEM and STEM: a new 3D imaging technique.
AB  - This paper presents the development and the application of a new electron
      tomography technique based on STEM (Scanning Transmission Electron Microscopy)
      configuration in ESEM (Environmental Scanning Electron Microscopy). This
      combination provides a new approach for the characterization of the 3D structure
      of materials, as it optimizes a compromise between the resolution level of a few
      tens of nm and the large tomogram size due to the high thickness of transparency.
      The method is well adapted for non-conductive samples, and exhibits good contrast
      even for materials with low atomic number. The paper describes the development of
      a dedicated stage for this new tomography technique. Taking advantage of the size
      of the ESEM chamber, the range of tilt angles is not limited by the space around
      the sample. The performance of this device is illustrated through the three
      dimensional characterization of samples issued from materials science and chosen
      to illustrate the results in resolution, contrast and thickness.

PMID- 21864763
TI  - Bedpan washer disinfectors: an in-use evaluation of cleaning and disinfection.
AB  - BACKGROUND: As part of a comprehensive approach to decreasing Clostridium
      difficile in our health authority, an evaluation of the in-use performance of 2
      brands of bedpan decontaminators (BPDs) in 2 acute care facilities was performed.
      METHODS: A continuous quality improvement approach consisting of 5 BPD audits and
      4 intervention phases was used over a 16-month evaluation period. Visible fecal
      soil on processed items was used as the progress indicator, and infection
      preventionists performed audits. RESULTS: A total of 1,982 observations was
      recorded. Percent failures rates ranged from 7.6% to 33% dependent on the
      intervention phase. Polypropylene materials had fewer failures compared with
      stainless steel. The addition of rinse agent significantly improved results
      particularly in polypropylene items (1% failure rate). A number of human factors
      issues and equipment design features compromised the BPD's ability to function
      adequately. CONCLUSION: Users should thoroughly evaluate the in-use efficacy of
      BPDs and use a step-wise approach to identify and correct both human and
      equipment deficiencies. Forced function and compliance features for correct
      loading of machines, detergent and rinse agent dispensing, and ability to operate
      the machine only when detergent is present should be integral to the BPD design.

PMID- 21864765
TI  - Toward quantitative core-loss EFTEM tomography.
AB  - Core-loss EFTEM tomography provides three-dimensional structural and chemical
      information. Multiple inelastic scattering occurring in thick specimens as well
      as orientation-dependent diffraction contrast due to multiple elastic scattering,
      however, often limit its applications. After demonstrating the capability of core
      loss EFTEM tomography to reconstruct just a few monolayers thin carbon layer
      covering a Fe catalyst particle we discuss its application to thicker samples. We
      propose an approximate multiple-scattering correction method based on the use of
      zero-loss images and apply it successfully to copper whiskers, providing a
      significant improvement of the reconstructed 3D elemental distribution. We
      conclude this paper by a general discussion on experimental parameters affecting
      the accuracy of EFTEM 3D elemental mapping.

PMID- 21864766
TI  - Exploring different inelastic projection mechanisms for electron tomography.
AB  - Several different projection mechanisms that all make use of inelastically
      scattered electrons are used for electron tomography. The advantages and the
      disadvantages of these methods are compared to HAADF-STEM tomography, which is
      considered as the standard electron tomography technique in materials science.
      The different inelastic setups used are energy filtered transmission electron
      microscopy (EFTEM), thickness mapping based on the log-ratio method and bulk
      plasmon mapping. We present a comparison that can be used to select the best
      inelastic signal for tomography, depending on different parameters such as the
      beam stability and nature of the sample. The appropriate signal will obviously
      also depend on the exact information which is requested.

PMID- 21864767
TI  - Study of the crystallographic architecture of corals at the nanoscale by scanning
      transmission X-ray microscopy and transmission electron microscopy.
AB  - We have investigated the nanotexture and crystallographic orientation of
      aragonite in a coral skeleton using synchrotron-based scanning transmission X-ray
      microscopy (STXM) and transmission electron microscopy (TEM). Polarization
      dependent STXM imaging at 40-nm spatial resolution was used to obtain an
      orientation map of the c-axis of aragonite on a focused ion beam milled ultrathin
      section of a Porites coral. This imaging showed that one of the basic units of
      coral skeletons, referred to as the center of calcification (COC), consists of a
      cluster of 100-nm aragonite globules crystallographically aligned over several
      micrometers with a fan-like distribution and with the properties of single
      crystals at the mesoscale. The remainder of the skeleton consists of aragonite
      single-crystal fibers in crystallographic continuity with the nanoglobules
      comprising the COC. Our observation provides information on the nm-scale
      processes that led to biomineral formation in this sample. Importantly, the
      present study illustrates how the methodology described here, which combines
      HRTEM and polarization-dependent synchrotron-based STXM imaging, offers an
      interesting new approach for investigating biomineralizing systems at the nm
      scale.

PMID- 21864768
TI  - Visualization of vortex core polarity in NiFe nanodots by tilted Fresnel images.
AB  - We illustrate an approach which allows determining the out-of-plane component of
      the vortex core (polarity) in NiFe nanodots using Fresnel imaging in Lorentz
      electron microscopy. Using tilted Fresnel images, contribution of the polarity is
      introduced into the Fresnel image. However, this contribution is relatively small
      and a difference image from two symmetrically tilted Fresnel images must be used
      to eliminate the strong contribution from the in-plane curling magnetization and
      non-magnetic contrast. The sense of the polarity appears as a bipolar white-black
      contrast in the difference image on the tilt axis. A vortex core with a diameter
      of 16.5 +/- 2.5 nm is experimentally measured. Image tilting, displacement and
      geometrical distortion may disturb the difference image, and hence subtraction of
      the difference image must be aligned by cross-correlation. The method is also
      justified by a study of the observed contrast characteristic due to misalignment.
      The method is confirmed to be superior to similar approach with direct
      interpretation of information and more information subtracted.

PMID- 21864769
TI  - Pragmatic reconstruction methods in atom probe tomography.
AB  - Data collected in atom probe tomography have to be carefully analysed in order to
      give reliable composition data accurately and precisely positioned in the probed
      volume. Indeed, the large analysed surfaces of recent instruments require
      reconstruction methods taking into account not only the tip geometry but also
      accurate knowledge of geometrical projection parameters. This is particularly
      crucial in the analysis of multilayers materials or planar interfaces. The
      current work presents a simulation model that enables extraction of the two main
      projection features as a function of the tip and atom probe instrumentation
      geometries. Conversely to standard assumptions, the image compression factor and
      the field factor vary significantly during the analysis. An improved
      reconstruction method taking into account the intrinsic shape of a sample
      containing planar features is proposed to overcome this shortcoming.

PMID- 21864770
TI  - Pawley and Rietveld refinements using electron diffraction from L12-type
      intermetallic Au3Fe1-x nanocrystals during their in-situ order-disorder
      transition.
AB  - During the in-situ order-disorder transition of intermetallic L1(2)-type
      Au(3)Fe(1-x) nanocrystals, structural information has been retrieved from their
      electron diffraction patterns based on the Pawley refinement that is unrelated to
      the electron kinematical or dynamical scattering nature as well as the Rietveld
      refinement using a kinematical approximation. At room temperature, it was found
      that the nanocrystals contain approximately x=40% vacancies at the Fe site. Based
      on in-situ heating this phase displayed an irreversible order-disorder
      transition, with the transition temperature between 553 and 593 K. A sudden
      increase in lattice parameter was detected during the first heating from the
      ordered phase, while the second heating of the disordered phase showed only a
      linear relationship with temperature. From the lattice parameter measurement of
      the disordered phase, the coefficient of thermal expansion was estimated as 1.462
      * 10(-5)K(-1). The long-range order parameter S was determined by the refined
      site occupancies, as well as the integrated intensities of the superlattice (100)
      and fundamental (220) reflections using the Pawley and Rietveld refinements
      during the order-disorder transition. Considering the dynamical scattering
      effect, Blackman two-beam approximation theory was applied to corrected S, which
      slightly attenuated after the correction. A comparison of the electron
      diffraction with X-ray diffraction data was made. It was demonstrated that
      elemental and structural information could be retrieved through quantitative
      electron diffraction studies of the nanomaterials. Since the Pawley refinement
      algorithm does not include the electron scattering event, it is especially useful
      to refine the electron diffraction data regardless of the sample thickness.

PMID- 21864771
TI  - Optimizing the phase shift and the cut-on periodicity of phase plates for TEM.
AB  - Images acquired with a phase plate often exhibit fringing and/or contrast
      reversal artifacts. The two basic parameters controlling the performance of the
      phase plate are phase shift and cut-on periodicity. We investigate theoretically
      and numerically the effect of these parameters on the image quality. The analysis
      covers not just the typical negative phase shift phase plates but also positive
      phase shift ones. The theoretical study derives formulas for calculating the
      optimal phase plate phase shift and for the maximum achievable contrast with a
      given specimen. Two figures of merit - fidelity and contrast - were defined and
      used to quantify the numerical results. Larger cut-on periodicities provide
      better performance with higher contrast and less artifacts in the images. Both,
      the theoretical results and the simulations indicate that positive phase shift
      phase plates generate higher contrast with better linearity and are free from
      contrast reversal artifacts. However, with such phase plates the amplitude and
      the phase contrast components are opposed to each other and the simulations show
      stronger fringing outside of objects. Based on these results it is difficult to
      predict if and to what extent the positive phase shift phase plates will be
      advantageous in practice. Two methods for reduction of fringing artifacts were
      compared-tapered phase plate and low-frequency amplification software filter.
      Overall the software solution produced better results and is much easier to
      implement than modifying the hardware of the phase plate to realize the taper.

PMID- 21864772
TI  - Composition mapping in InGaN by scanning transmission electron microscopy.
AB  - We suggest a method for chemical mapping that is based on scanning transmission
      electron microscopy (STEM) imaging with a high-angle annular dark field (HAADF)
      detector. The analysis method uses a comparison of intensity normalized with
      respect to the incident electron beam with intensity calculated employing the
      frozen lattice approximation. This procedure is validated with an
      In(0.07)Ga(0.93)N layer with homogeneous In concentration, where the STEM results
      were compared with energy filtered imaging, strain state analysis and energy
      dispersive X-ray analysis. Good agreement was obtained, if the frozen lattice
      simulations took into account static atomic displacements, caused by the
      different covalent radii of In and Ga atoms. Using a sample with higher In
      concentration and series of 32 images taken within 42 min scan time, we did not
      find any indication for formation of In rich regions due to electron beam
      irradiation, which is reported in literature to occur for the parallel
      illumination mode. Image simulation of an In(0.15)Ga(0.85)N layer that was
      elastically relaxed with empirical Stillinger-Weber potentials did not reveal
      significant impact of lattice plane bending on STEM images as well as on the
      evaluated In concentration profiles for specimen thicknesses of 5, 15 and 50 nm.
      Image simulation of an abrupt interface between GaN and In(0.15)Ga(0.85)N for
      specimen thicknesses up to 200 nm showed that artificial blurring of interfaces
      is significantly smaller than expected from a simple geometrical model that is
      based on the beam convergence only. As an application of the method, we give
      evidence for the existence of In rich regions in an InGaN layer which shows
      signatures of quantum dot emission in microphotoluminescence spectroscopy
      experiments.

PMID- 21864773
TI  - Dark-field electron holography for the measurement of geometric phase.
AB  - The genesis, theoretical basis and practical application of the new electron
      holographic dark-field technique for mapping strain in nanostructures are
      presented. The development places geometric phase within a unified theoretical
      framework for phase measurements by electron holography. The total phase of the
      transmitted and diffracted beams is described as a sum of four contributions:
      crystalline, electrostatic, magnetic and geometric. Each contribution is outlined
      briefly and leads to the proposal to measure geometric phase by dark-field
      electron holography (DFEH). The experimental conditions, phase reconstruction and
      analysis are detailed for off-axis electron holography using examples from the
      field of semiconductors. A method for correcting for thickness variations will be
      proposed and demonstrated using the phase from the corresponding bright-field
      electron hologram.

PMID- 21864774
TI  - Ion beam nanopatterning and micro-Raman spectroscopy analysis on HOPG for testing
      FIB performances.
AB  - This work reports Ga(+) focused ion beam nanopatterning to create amorphous
      defects with periodic square arrays in highly oriented pyrolytic graphite and the
      use of Raman spectroscopy as a new protocol to test and compare progresses in ion
      beam optics, for low fluence bombardment or fast writing speed. This can be
      ultimately used as a metrological tool for comparing different FIB machines and
      can contribute to Focused Ion Beam (FIB) development in general for tailoring
      nanostructures with higher precision. In order to do that, the amount of ion at
      each spot was varied from about 10(6) down to roughly 1 ion per dot. These
      defects were also analyzed by using high resolution scanning electron microscopy
      and atomic force microscopy. The sensitivities of these techniques were compared
      and a geometrical model is proposed for micro-Raman spectroscopy in which the
      intensity of the defect induced D band, for a fixed ion dose, is associated with
      the diameter of the ion beam. In addition, the lateral increase in the bombarded
      spot due to the cascade effect of the ions on graphite surface was extracted from
      this model. A semi-quantitative analysis of the distribution of ions at low doses
      per dot or high writing speed for soft modification of materials is discussed.

PMID- 21864775
TI  - The effect of electron range on electron beam induced current collection and a
      simple method to extract an electron range for any generation function.
AB  - The effect of electron range on electron beam induced current (EBIC) is
      demonstrated and the problem of the choice of the optimal electron ranges to use
      with simple uniform and point generation function models is resolved by proposing
      a method to extract an electron range-energy relationship (ERER). The results
      show that the use of these extracted electron ranges remove the previous
      disagreement between the EBIC curves computed with simple forms of generation
      model and those based on a more realistic generation model. The impact of these
      extracted electron ranges on the extraction of diffusion length, surface
      recombination velocity and EBIC contrast of defects is discussed. It is also
      demonstrated that, for the case of uniform generation, the computed EBIC current
      is independent of the assumed shape of the generation volume.

PMID- 21864776
TI  - A method to determine the local surface profile from reconstructed exit waves.
AB  - Reconstructed exit waves are useful to quantify unknown structure parameters such
      as the position and composition of the atom columns at atomic scale. Existing
      techniques provide a complex wave in a flat plane which is close to the plane
      where the electrons leave the atom columns. However, due to local deviation in
      the flatness of the exit surface, there will be an offset between the plane of
      reconstruction and the actual exit of a specific atom column. Using the
      channelling theory, it has been shown that this defocus offset can in principle
      be determined atom column-by-atom column. As such, the surface roughness could be
      quantified at atomic scale. However, the outcome strongly depends on the initial
      plane of reconstruction especially in a crystalline structure. If this plane is
      further away from the true exit, the waves of the atom columns become delocalized
      and interfere mutually which strongly complicates the interpretation of the exit
      wave in terms of the local structure. In this paper, we will study the
      delocalization with defocus using the channelling theory in a more systematic
      way.

PMID- 21864777
TI  - Quantitative magnetic force microscopy on permalloy dots using an iron filled
      carbon nanotube probe.
AB  - An iron filled carbon nanotube (FeCNT), a 10-40 nm ferromagnetic nanowire
      enclosed in a protective carbon tube, is an attractive candidate for a magnetic
      force microscopy (MFM) probe as it provides a mechanically and chemically robust,
      nanoscale probe. We demonstrate the probe's capabilities with images of the
      magnetic field gradients close to the surface of a Py dot in both the multi
      domain and vortex states. We show the FeCNT probe is accurately described by a
      single magnetic monopole located at its tip. Its effective magnetic charge is
      determined by the diameter of the iron wire and its saturation magnetization
      4piM(s) ~ 2.2 * 10(4)G. A magnetic monopole probe is advantageous as it enables
      quantitative measurements of the magnetic field gradient close to the sample
      surface. The lateral resolution is defined by the diameter of the iron wire and
      the probe-sample separation.

PMID- 21864778
TI  - Broadband nanodielectric spectroscopy by means of amplitude modulation
      electrostatic force microscopy (AM-EFM).
AB  - In this work we present a new AFM based approach to measure the local dielectric
      response of polymer films at the nanoscale by means of Amplitude Modulation
      Electrostatic Force Microscopy (AM-EFM). The proposed experimental method is
      based on the measurement of the tip-sample force via the detection of the second
      harmonic component of the photosensor signal by means of a lock-in amplifier.
      This approach allows reaching unprecedented broad frequency range (2-3 * 10(4)Hz)
      without restrictions on the sample environment. The method was tested on
      different poly(vinyl acetate) (PVAc) films at several temperatures. Simple
      analytical models for describing the electric tip-sample interaction semi
      quantitatively account for the dependence of the measured local dielectric
      response on samples with different thicknesses and at several tip-sample
      distances.

PMID- 21864779
TI  - A study of phase separated Ni66Nb17Y17 metallic glass using atom probe
      tomography.
AB  - Microstructural characterization of Ni(66)Nb(17)Y(17) as spun metallic glass
      ribbon was carried out using atom probe tomography. A comparison of different
      experimental conditions for pulsed laser and pulsed voltage field evaporation
      reveal that the laser pulsing can be optimized to avoid preferential evaporation
      of yttrium. Atom probe tomography measurements illustrate that the sample
      undergoes phase separation resulting in two interconnected phases during the
      process of vitrification. The yttrium-enriched phase was depleted in niobium and
      yttrium-depleted phase was enriched in niobium. Moreover, detailed analyses of
      the roller-contact and non-contact sides of the melt-spun ribbon show different
      wavelength of phase separated regions revealing that the degree of phase
      separation is directly associated with the cooling rate.

PMID- 21864780
TI  - Effect of sample thickness, energy filtering, and probe coherence on fluctuation
      electron microscopy experiments.
AB  - We have explored experimentally the effects of the TEM sample thickness, zero
      loss energy filtering, and probe coherence on fluctuation electron microscopy
      (FEM) experiments implemented using nanodiffraction. FEM measures the variance V
      of spatial fluctuations in nanodiffraction. We find that V is inversely
      proportional to the sample thickness, as predicted by earlier models. Energy
      filtering increases V at all thicknesses we measured. V increases as the
      coherence of the probe increases. All of these factors must be carefully
      controlled to obtain quantitatively reliable FEM data.

PMID- 21864781
TI  - High energy-resolution electron energy-loss spectroscopy study of the dielectric
      properties of bulk and nanoparticle LaB6 in the near-infrared region.
AB  - The dielectric properties of LaB(6) crystals and the plasmonic behavior of LaB(6)
      nanoparticles, which have been applied to solar heat-shielding filters, were
      studied by high energy-resolution electron energy-loss spectroscopy (HR-EELS). An
      EELS spectrum of a LaB(6) crystal showed a peak at 2.0 eV, which was attributed
      to volume plasmon excitation of carrier electrons. EELS spectra of single LaB(6)
      nanoparticles showed peaks at 1.1-1.4 eV depending on the dielectric effect from
      the substrates. The peaks were assigned to dipole oscillation excitations. These
      peak energies almost coincided with the peak energy of optical absorption of a
      heat-shielding filter with LaB(6) nanoparticles. On the other hand, those
      energies were a smaller than a dipole oscillation energy predicted using the
      dielectric function of bulk LaB(6) crystal. It is suggested that the lower energy
      than expected is due to an excitation at 1.2 eV, which was observed for oxidized
      LaB(6) area.

PMID- 21864782
TI  - Optimizing the driving scheme of a self-actuated atomic force microscope probe
      for high-speed applications.
AB  - We investigate the optimum driving scheme of a dynamic atomic force microscope
      with a self-actuated probe for high-speed applications by performing numerical
      simulations. We compare the recently developed methods such as Q-control, dynamic
      PID control, and modified Q-control methods to the standard tapping mode by
      considering scan speed and peak transient forces. In addition, the effects of
      driving frequency and set-point amplitude on the maximum achievable scan speed
      for the same probe-sample system are discussed. We find that the scan speed can
      be increased significantly at the expense of increased peak transient forces.

PMID- 21864783
TI  - Measurement of residual elastic strain and lattice rotations with high resolution
      electron backscatter diffraction.
AB  - A set of dynamically simulated electron backscatter patterns (EBSPs) for alpha-Ti
      crystals progressively rotated by 1 degrees  steps were analysed using cross
      correlation to determine image shifts from which strains and rotations were
      calculated. At larger rotations the cross-correlation fails in certain regions of
      the EBSP where large shifts are generated. These incorrect shifts prevent
      standard least square error procedures from obtaining a valid solution for the
      strain and rotation, where the applied rotation exceeds ~ 8 degrees . Using a
      robust iterative fitting routine reliable strains and rotations can be obtained
      for applied rotations of up to and including ~ 11 degrees  even though some image
      shifts are measured incorrectly. Finally, high resolution electron backscatter
      diffraction has been used to analyse the residual elastic strain, lattice
      rotations and density of stored geometrically necessary dislocations in a sample
      of copper deformed to 10% total strain. The robust iterative fitting analysis
      allows reliable analysis of a larger proportion of the map, the difference being
      most obviously beneficial in regions where significant lattice rotations have
      been generated.

PMID- 21864784
TI  - Detection of buried reference structures by use of atomic force acoustic
      microscopy.
AB  - The miniaturization of micro- and nanoelectronic components requires new methods
      for the inspection of buried inner structures at the nanoscale. We used the
      atomic force acoustic microscopy technique (AFAM) to image subsurface defects.
      This technique combines high lateral resolution with the capability to determine
      local elastic properties of materials near the surface. As the structures buried
      near the surface change the effective tip-sample contact stiffness it is possible
      to detect them. For the verification of the detection capabilities of AFAM we
      fabricated well-defined buried void structures with different geometries and
      dimensions. Large, thin, plate like structures of silicon nitride with a local
      filling were our first test samples. Then, sets of nine small, square, thin
      plates with thicknesses increasing stepwise from 30 to 270 nm were etched in a
      thinned silicon wafer. The last two samples contained wedge structures of widths
      varying between 1.6 and 10 MUm. Our results showed that it was possible to detect
      buried void structures at depths between 180 and 900 nm. We also observed that
      the depths at which the buried defects can be detected by the use of the AFAM
      method depend on the defect dimensions and geometry, and on the mismatch in the
      elastic properties of the sample and the defects. The experimental results
      obtained for the groups of small, thin plates were verified by quantitative
      analysis via finite element method (FEM) simulations.

PMID- 21864785
TI  - Investigation of morphological and functional changes during neuronal
      differentiation of PC12 cells by combined hopping probe ion conductance
      microscopy and patch-clamp technique.
AB  - PC12 cells derived from rat pheochromocytoma can differentiate into sympathetic
      neuron-like cells in response to nerve growth factor (NGF). These cells have been
      proved to be a useful cell model to study neuronal differentiation. NGF induces
      rapid changes in membrane morphology, neurite outgrowth, and electrical
      excitability. However, the relationship between the 3D morphological changes of
      NGF-differentiated PC12 cells and their electrophysiological functions remains
      poorly understood. In this study, we combined a recently developed Hopping Probe
      Ion Conductance Microscopy (HPICM) with patch-clamp technique to investigate the
      high-resolution morphological changes and functional ion-channel development
      during the NGF-induced neuronal differentiation of PC12 cells. NGF enlarged TTX
      sensitive sodium currents of PC12 cells, which associated with cell volume,
      membrane surface area, surface roughness of the membrane, and neurite outgrowth.
      These results demonstrate that the combination of HPICM and patch-clamp technique
      can provide detailed information of membrane microstructures and ion-channel
      functions during the differentiation of PC12 cells, and has the potential to
      become a powerful tool for neuronal research.

PMID- 21864786
TI  - Influence of the tip mass on the tip-sample interactions in TM-AFM.
AB  - This paper focuses on the influences of the tip mass ratio (the ratio of the tip
      mass to the cantilever mass), on the excitation of higher oscillation eigenmodes
      and also on the tip-sample interaction forces in tapping mode atomic force
      microscopy (TM-AFM). A precise model for the cantilever dynamics capable of
      accurate simulations is essential for the investigation of the tip mass effects
      on the interaction forces. In the present work, the finite element method (FEM)
      is used for modeling the AFM cantilever to consider the oscillations of higher
      eigenmodes oscillations. In addition, molecular dynamics (MD) is used to
      calculate precise data for the tip-sample force as a function of tip vertical
      position with respect to the sample. The results demonstrate that in the presence
      of nonlinear tip-sample interaction forces, the tip mass ratio plays a
      significant role in the excitations of higher eigenmodes and also in the normal
      force applied on the surface. Furthermore, it has been shown that the difference
      between responses of the FEM and point-mass models in different system
      operational conditions is highly affected by the tip mass ratio.

PMID- 21864787
TI  - Practical methods for the measurement of spatial coherence--a comparative study.
AB  - Two new methods for the measurement of transverse spatial coherence in a
      transmission electron microscope (TEM) are developed and applied to measure the
      spatial coherence in a field emission gun TEM. Measurements are made under
      different illumination and operating conditions, illustrating the effect of these
      conditions on the spatial coherence. The relative merits and limitations of these
      methods are discussed and compared, together with the previously described
      "Ronchigram" method.

PMID- 21864788
TI  - [110 years ago: Wilhelm Conrad Roentgen received the first Nobel Prize].

PMID- 21864790
TI  - Self-organizing map of gene regulatory networks for cell phenotypes during
      reprogramming.
AB  - The induced pluripotent cells (iPSCs) are derived from somatic cells by
      reprogramming their genetic profiles. Such a process requires coordinated dynamic
      expression of hundreds of genes and proteins. As both deterministic and
      stochastic elements control the reprogramming process, it is not easy to have a
      way to reflect the status of gene regulatory network in those reprogramming
      cells. In this study, we applied self-organizing maps (SOMs) on those complex
      gene expression data from different pluripotent cells, including partially
      reprogrammed and fully reprogrammed induced pluripotent cells (iPSCs), embryonic
      stem cells (ESCs), and adult stem cells came from different tissues. We showed
      that our SOMs have good correlation with the previously reported PluriNet of stem
      cells and they are pictorial diagrams which can reflect the intrinsic status of
      cells.

PMID- 21864791
TI  - CE-PLoc: an ensemble classifier for predicting protein subcellular locations by
      fusing different modes of pseudo amino acid composition.
AB  - Precise information about protein locations in a cell facilitates in the
      understanding of the function of a protein and its interaction in the cellular
      environment. This information further helps in the study of the specific
      metabolic pathways and other biological processes. We propose an ensemble
      approach called "CE-PLoc" for predicting subcellular locations based on fusion of
      individual classifiers. The proposed approach utilizes features obtained from
      both dipeptide composition (DC) and amphiphilic pseudo amino acid composition
      (PseAAC) based feature extraction strategies. Different feature spaces are
      obtained by varying the dimensionality using PseAAC for a selected base learner.
      The performance of the individual learning mechanisms such as support vector
      machine, nearest neighbor, probabilistic neural network, covariant discriminant,
      which are trained using PseAAC based features is first analyzed. Classifiers are
      developed using same learning mechanism but trained on PseAAC based feature
      spaces of varying dimensions. These classifiers are combined through voting
      strategy and an improvement in prediction performance is achieved. Prediction
      performance is further enhanced by developing CE-PLoc through the combination of
      different learning mechanisms trained on both DC based feature space and PseAAC
      based feature spaces of varying dimensions. The predictive performance of
      proposed CE-PLoc is evaluated for two benchmark datasets of protein subcellular
      locations using accuracy, MCC, and Q-statistics. Using the jackknife test,
      prediction accuracies of 81.47 and 83.99% are obtained for 12 and 14 subcellular
      locations datasets, respectively. In case of independent dataset test, prediction
      accuracies are 87.04 and 87.33% for 12 and 14 class datasets, respectively.

PMID- 21864792
TI  - Performance assessment of different constraining potentials in computational
      structure prediction for disulfide-bridged proteins.
AB  - The presence of disulfide bonds in proteins has very important implications on
      the three-dimensional structure and folding of proteins. An adequate treatment of
      disulfide bonds in de-novo protein simulations is therefore very important. Here
      we present a computational study of a set of small disulfide-bridged proteins
      using an all-atom stochastic search approach and including various constraining
      potentials to describe the disulfide bonds. The proposed potentials can easily be
      implemented in any code based on all-atom force fields and employed in
      simulations to achieve an improved prediction of protein structure. Exploring
      different potential parameters and comparing the structures to those from
      unconstrained simulations and to experimental structures by means of a scoring
      function we demonstrate that the inclusion of constraining potentials improves
      the quality of final structures significantly. For some proteins (1KVG and 1PG1)
      the native conformation is visited only in simulations in presence of
      constraints. Overall, we found that the Morse potential has optimal performance,
      in particular for the beta-sheet proteins.

PMID- 21864793
TI  - Exploring and characterizing the folding processes of Lys- and Arg-containing Ala
      based peptides: a molecular dynamics study.
AB  - In this study, molecular dynamics simulations were carried out on Lys- and Arg
      containing Ala-based peptides (i.e. Ace-(AAAAK)(n)A-NH(2) and Ace-(AAAAR)(n)A
      NH(2), where n=1-4), in order to explore and characterize their folding
      processes. For the oligopeptides, the evolution of alpha-helical structure with
      regard to the whole conformation, as well as to each residue was investigated,
      and the helix-forming propensities were characterized. On the basis of the
      helicity curves, representing the alteration of average helicity as a function of
      time, the typical time values describing the folding processes and subprocesses
      were identified. In the case of each peptide, the evolution and role of helix
      stabilizing, non-local and side-chain-to-backbone H-bonds were examined. The
      appearing i<-i+4 H-bonds pointed out the role of these interactions in the
      stabilization of alpha-helical conformations, while the occurring i<-i+3 H-bonds
      indicated the presence of beta-turn or 3(10)-helical structures. Studying the
      formation and role of non-local and side-chain-to-backbone H-bonds led to the
      observation that these types of interactions produced an effect on the evolution
      of helical conformations, as well as on the folding processes.

PMID- 21864794
TI  - An integer programming approach to DNA sequence assembly.
AB  - De novo sequence assembly is a ubiquitous combinatorial problem in all DNA
      sequencing technologies. In the presence of errors in the experimental data, the
      assembly problem is computationally challenging, and its solution may not lead to
      a unique reconstruct. The enumeration of all alternative solutions is important
      in drawing a reliable conclusion on the target sequence, and is often overlooked
      in the heuristic approaches that are currently available. In this paper, we
      develop an integer programming formulation and global optimization solution
      strategy to solve the sequence assembly problem with errors in the data. We also
      propose an efficient technique to identify all alternative reconstructs. When
      applied to examples of sequencing-by-hybridization, our approach dramatically
      increases the length of DNA sequences that can be handled with global optimality
      certificate to over 10,000, which is more than 10 times longer than previously
      reported. For some problem instances, alternative solutions exhibited a wide
      range of different ability in reproducing the target DNA sequence. Therefore, it
      is important to utilize the methodology proposed in this paper in order to obtain
      all alternative solutions to reliably infer the true reconstruct. These
      alternative solutions can be used to refine the obtained results and guide the
      design of further experiments to correctly reconstruct the target DNA sequence.

PMID- 21864796
TI  - Photodynamic therapy (PDT) for lung cancer.
AB  - Clinical PDT began in the early 1980s and lung cancer was one of the first
      indications for which the procedure was tried. Initially patients with advanced
      inoperable cancer and major bronchial obstruction were targeted with the
      objective of relief of airway obstruction and symptom palliation. In the past 30
      years, assisted by progress in imaging methods and advances of technological
      developments, PDT indications have expanded to incorporate a multitude of lung
      cancer presentations which this review aims to display. Locally advanced and
      early stage endobronchial cancer continues to be the major indications albeit
      with a more precise diagnostic and guided illumination devices. Peripheral
      parenchymal disease has been a technical challenge but there is still ongoing
      development. Multifocal synchronous, recurrence and metachronous endobronchial
      disease following lung resection are now an up and coming indication with
      rewarding outcome. More importantly PDTs role within a multi-disciplinary assault
      on lung cancer is receiving acceptance.

PMID- 21864797
TI  - The application of photosensitisers to tropical pathogens in the blood supply.
AB  - The onset of the HIV pandemic led both to significant alterations in blood
      collection and screening practice and to the development of more sophisticated
      methods of inactivation of infectious agents from the blood supply. Photodynamic
      (i.e. light activated) pathogen inactivation is one such method currently in
      limited use in various European states. The approach is based on the generation
      of a burst of reactive oxygen and nitrogen species, resulting in the activation
      of several cell death mechanisms. However, its application to tropical pathogens
      is perhaps less appreciated, despite the fact that the efficacies of
      photoantimicrobial agents such as methylene blue were originally reported
      following screening against organisms such as Trypanosoma cruzi and viruses such
      as those responsible for dengue and yellow fever. Since the objective of pathogen
      inactivation is to remove both established and emerging infective agents, it is
      necessary for photoantimicrobial agents to be broad-spectrum in activity. While
      this is demonstrable in plasma and platelet fractions, the application to red
      blood cells is currently under investigation.

PMID- 21864798
TI  - Evaluation of the effect of photoactivated disinfection with Radachlorin((r))
      against Streptococcus mutans (an in vitro study).
AB  - BACKGROUND: The use of photoactivated disinfection has had a significant medical
      and technological effect in bacterial inactivation, as an alternative to
      conventional antimicrobial methods. The main goal of this study was to
      investigate the effect of photoactivated disinfection on Streptococcus mutans,
      when Radachlorin((r)) was used as a photosensitizer. METHODS: Streptococcus
      mutans samples of two different initial concentrations were treated with
      Radachlorin((r)) gel (0.1%), irradiated by the light of a He-Ne laser (633nm),
      with energy density of 6J/cm(2), and cell viability was evaluated after
      culturing. RESULTS: It was observed that the combination of Radachlorin((r)) and
      laser was more effective than Radachlorin((r)) or laser alone (p<0.05), in
      reduction of S. mutans and Radachlorin((r)) was cytotoxic, in the dark, only for
      the lower concentration of bacteria. Lower concentration of S. mutans resulted in
      higher amount of killing, in the case of using Radachlorin((r)) with or without
      laser. CONCLUSIONS: The photoactivation of Radachlorin((r)) using a He-Ne laser
      could inactivate S. mutans to a significant level. In addition Radachlorin((r))
      might be cytotoxic in the dark, for the lower concentration of bacteria.

PMID- 21864799
TI  - Photodynamic therapy (PDT) - Initiation of apoptosis via activation of stress
      activated p38 MAPK and JNK signal pathway in H460 cell lines.
AB  - AIMS: The purpose of this study was to investigate the photoefficacies of
      protoporphyrin IX (PpIX) generated by drug precursor 5-aminolevulinic acid (ALA)
      and its hexyl ester (H-ALA) on two human non-small lung carcinoma cell lines
      (H460/Bcl-2 and H460/neo). MAIN METHODS: Drug uptake and the photoefficacies of
      PpIX were measured by flow cytometry and MTT assay; while the mode of cell death
      and alternation of signal transduction pathways were studied with 4',6-diamidino
      2-phenylindole (DAPI) staining and Western blot analysis, respectively. KEY
      FINDINGS: The flow cytometric analysis of H-ALA (5MUM) uptake revealed optimal
      fluorescent intensity at 8h incubation, while ALA (0.5mM) was still far from
      saturation. The LD(30) of H-ALA-PDT was 30MUM, 2J/cm(2), while the LD(30) of ALA
      PDT was 3mM, 2J/cm(2). The dark toxicities mediated by both pro-drug H-ALA and
      ALA were negligible. By DAPI staining, apoptotic cell death was observed. In
      addition, by Western blot analysis, H-ALA- and ALA-mediated PDT initiated
      apoptotic cell death via the up-regulation and activation of p38 mitogen
      activated protein kinase (MAPK), the stress-activated c-jun N-terminal kinases
      (JNK) and ERK. SIGNIFICANCE: These results suggested that H-ALA and ALA mediated
      PDT displayed similar photocytotoxicities towards the two non-small lung cancer
      cells. Our present study also demonstrates H-ALA or ALA mediated PDT in H460
      cells are closely related to the activation of p38 MAPK and JNK signalling
      pathway.

PMID- 21864800
TI  - Surgical debulking combined with photodynamic therapy to manage residual
      extramedullary plasmacytoma of the nasopharynx.
AB  - Extramedullary plasmacytomas (EMP) are rare plasma cell neoplasms that are mostly
      located in the mucosal surfaces of the upper aerodigestive tract. The standard
      treatment is radiotherapy (RT), with surgical resection reserved as salvage
      procedure. In this report a patient with a EMP, located in the nasopharynx and
      refractory to curative RT. Because of the technical difficulty of a radical
      resection in the nasopharynx area the EMP is managed by endoscopic debulking and
      temoporfin mediated photodynamic therapy. The patient remains disease free since
      six years.

PMID- 21864801
TI  - Optimal light dose and drug dosage in the photodynamic treatment using
      PHOTOCYANINE.
AB  - BACKGROUND: To explore the effective dose range of PHOTOCYANINE, the intensity
      and duration of irradiation using a 670-nm laser, and changes of local tissues
      after photodynamic therapy (PDT) in mice with S180 tumors to provide evidence for
      the clinical application of PDT. BASIC METHODS: Kunming mice were administered
      the photosensitizer PHOTOCYANINE. After the administration of PHOTOCYANINE,
      irradiation with 670-nm laser had a remarkable inhibitory effect on the growth of
      the grafted tumor S180. MAIN RESULTS: Within the power densities 36-144J/cm(2),
      the irradiation dose showed a significant dose-response relationship; under the
      same drug dosage, an increase in irradiation dose could enhance the inhibitory
      effect on tumor growth. In the groups administered PHOTOCYANINE and irradiated
      with a 670-nm laser, the temperature of the local surface did not increase
      remarkably, an effect also seen in the negative control group. Local swelling
      around the tumor occurred immediately after PHOTOCYANINE administration and laser
      irradiation, and could last for about 3 days. Vertical resection of the tumors 72
      h after irradiation showed that the depth of local-tissue necrosis after
      PHOTOCYANINE administration and laser irradiation was 5.7-7.5mm. PRINCIPAL
      CONCLUSIONS: The efficacy of PHOTOCYANINE was significantly correlated with its
      dose; under identical irradiation conditions, the increase in drug dose increased
      the tumor inhibition rate (TIR) within a certain dose range. The efficacy of
      PHOTOCYANINE also showed significant irradiation-dependent characteristics.

PMID- 21864802
TI  - Photobleaching-based method to individualize irradiation time during interstitial
      5-aminolevulinic acid photodynamic therapy.
AB  - Interstitial photodynamic therapy (iPDT) is being investigated for the treatment
      of high-grade human brain malignancies. In recent clinical studies, fluorescence
      monitoring during iPDT of glioblastoma multiforme has revealed patient-specific
      accumulation of photosensitizer (aminolevulinic acid (ALA) induced protoporphyrin
      IX, PpIX) and its photobleaching kinetics. As photosensitizer degradation, also
      referred to as photobleaching, and tissue damage are caused by the same
      underlying processes, the photobleaching kinetics might provide a tool for real
      time treatment supervision. Here, we show with computer simulations that varying
      optical properties have a strong influence on the irradiation time required to
      fully bleach the photosensitizer. We propose a method to potentially determine
      the time point during iPDT, when the photosensitizer within the target volume has
      been largely photobleached. Simulations show that it is possible to determine
      this time point by continuously monitoring the ratio of the fluorescence
      intensities at two time points during irradiation. We show that this method works
      for a large range of optical properties, different photobleaching rates and
      varying inter-fibre distances. In conclusion, the relative fluorescence method
      offers the potential to individualize irradiation times to consume the
      photosensitizer within the target tissue during iPDT.

PMID- 21864803
TI  - Biphasic dose-response of antioxidants in hypericin-induced photohemolysis.
AB  - In the present paper the photodynamic effect of hypericin on superoxide dismutase
      activity and the possibility of reduction of hypericin phototoxicity by
      antioxidants were studied. It was shown an almost twice decrease in superoxide
      dismutase activity of red blood cells under the photosensitization by hypericin.
      The influence of antioxidants (ascorbic acid and quercetin) on hypericin
      photodynamic action has revealed that these antioxidants suppress or stimulate
      photohemolysis caused by hypericin. The photosensitization reaction realized by
      hypericin could be shifted from type II to type I or vice versa by manipulating
      the antioxidant concentration. Strengthening of photohemolysis by antioxidants in
      some concentrations indicates the switching of alternative mechanisms of
      hypericin photodynamic action and its complicated manner. Thus the selection of
      antioxidant concentrations is of extreme importance for changing the efficacy of
      photodynamic therapy with hypericin.

PMID- 21864804
TI  - Championing photoantimicrobial discovery.

PMID- 21864806
TI  - A1C as the method for diagnosing diabetes--how wise is the choice?

PMID- 21864807
TI  - Advances on the interaction of polypyridyl Cr(III) complexes with transporting
      proteins and its potential relevance in photodynamic therapy.
AB  - The present study reports a detailed investigation into the interaction of
      [Cr(phen)(2)(dppz)](3+) and [Cr(phen)(3)](3+) with transferrin, the key protein
      for the transport of Fe(3+) in blood plasma; its cycle holds promise as an
      attractive system for strategies of drug targeting to tumor tissues. This can
      allow us to understand further the role of both complexes as sensitizers in
      photodynamic therapy (PDT). Chromium(III) complexes, [Cr(phen)(2)(dppz)](3+) and
      [Cr(phen)(3)](3+), (phen=1,10-phenanthroline and dppz=dipyridophenazine), where
      dppz is a planar bidentate ligand with an extended pi system, have been found to
      bind strongly with apotransferrin (apoTf) with an intrinsic binding constant,
      K(b), of (1.8+/-0.3)*10(5)M(-1) and (1.1+/-0.1)*10(5)M(-1) at 299K, for apoTf
      [Cr(phen)(2)(dppz)](3+) and apoTf-[Cr(phen)(3)](3+), respectively. The
      interactions of apoTf with the different Cr(III) complexes were assessed
      employing UV-visible absorption, fluorescence and circular dichroism
      spectroscopy. The relative fluorescence intensity of the protein decreased when
      the increasing concentration of Cr(III) complex was added, suggesting that
      perturbation around the Trp and Tyr residues took place. The analysis of the
      thermodynamic parameters DeltaG, DeltaH, DeltaS indicated that the presence of
      the Cr(III) complex stabilizes the protein with a strong entropic contribution.
      The binding distances and transfer efficiencies for apoTf-[Cr(phen)(2)(dppz)](3+)
      and apoTf-[Cr(phen)(3)](3+) binding reactions were calculated according to Foster
      theory of non-radiation energy transfer. All these experimental results suggest
      that [Cr(phen)(2)(dppz)](3+) and [Cr(phen)(3)](3+) bind strongly to apoTf
      indicating that this protein could act as a carrier of these complexes for
      further applications in PDT.

PMID- 21864808
TI  - Iminophosphorane-organogold(III) complexes induce cell death through
      mitochondrial ROS production.
AB  - Gold compounds are being investigated as potential antitumor drugs. Some
      gold(III) derivatives have been shown to induce cell death in solid tumors but
      their mechanism of action differs from that of cisplatin, since most of these
      compounds do not bind to DNA. We have explored cellular events triggered by three
      different iminophosphorane-organogold(III) compounds in leukemia cells (a neutral
      compound with two chloride ligands [Au{kappa(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))
      2}Cl(2)] 1, and two cationic compounds with either a dithiocarbamate ligand
      [Au{kappa(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(S(2)CN-Me(2))]PF(6)2, or a water
      soluble phosphine and a chloride ligand [Au{kappa(2)-C,N
      C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(P{Cp(m-C(6)H(4)-SO(3)Na)(2)}(3)) Cl]PF(6)3). All
      three compounds showed higher toxicity against leukemia cells when compared to
      normal T-lymphocytes. Compounds 1 and 2 induced both necrosis and apoptosis,
      while 3 was mainly apoptotic. Necrotic cell death induced by 1 and 2 was Bax/Bak-
      and caspase-independent, while apoptosis induced by 3 was Bax/Bak-dependent.
      Reactive oxygen species (ROS) production at the mitochondrial level was a
      critical step in the antitumor effect of these compounds.

PMID- 21864809
TI  - Iron binding of 3-hydroxychromone, 5-hydroxychromone, and sulfonated morin:
      Implications for the antioxidant activity of flavonols with competing metal
      binding sites.
AB  - The iron binding properties and antioxidant activities of compounds with hydroxy
      keto binding sites, 3-hydroxychromone, 5-hydroxychromone, and sulfonated morin
      were investigated. For these compounds, prevention of iron-mediated DNA damage
      and kinetics of Fe(II) oxidation were studied in aqueous solutions close to
      physiological pH (pH 6). 3-Hydroxychromone and sulfonated morin inhibit iron
      mediated DNA damage at lower concentrations than 5-hydroxychromone. All three
      compounds bind iron, but 3-hydroxychromone and sulfonated morin promote Fe(II)
      oxidation much faster than 5-hydroxychromone. These results indicate that DNA
      damage inhibition by flavonols with competing hydroxy-keto binding sites is
      primarily due to iron binding at the 3-hydroxy-keto site. Iron oxidation rate
      also plays a significant role in antioxidant activity. In addition to iron
      binding and oxidation, reactive oxygen species scavenging occurs at high
      concentrations for the hydroxychromones. This study emphasizes the importance of
      iron binding in polyphenol antioxidant behavior and provides insights into the
      iron binding antioxidant activity of similar flavonols such as quercetin and
      myricetin.

PMID- 21864810
TI  - Ternary oxovanadium(IV) complexes with amino acid-Schiff base and polypyridyl
      derivatives: synthesis, characterization, and protein tyrosine phosphatase 1B
      inhibition.
AB  - To investigate the structure-activity relationship of vanadium complexes in
      inhibiting protein tyrosine phosphatase1B (PTP1B), eight mixed-ligand
      oxovanadium(IV) complexes, [V(IV)O(SalAla)(NN)] (H(2)SalAla for salicylidene
      alanine, NN for N,N'-donor heterocyclic base, namely, 2,2'-bipyridine (bpy, 1),
      1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3),
      dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4)), [V(IV)O(SalLys)(dpq)] (5),
      [V(IV)O(SalLys)(dppz)] (6), [V(IV)O(SalAsp)(dppz)], (7) and
      [V(IV)O(SalTrp)(dppz)] (8)), of which 3-8 are new, have been prepared and
      characterized by elemental analysis, infrared, UV-visible, electrospray
      ionization mass spectrometry and conductivity. The molar conductance data
      confirmed the non-electrolytic nature of the complexes in DMSO solution. The
      coordination in [V(IV)O (SalAla)(phen)] (2) was confirmed by X-ray crystal
      structure analysis. The oxidation state of V(IV) with d(1) configuration in 2 was
      confirmed by EPR. The speciation of VO-SalAla-phen in aqueous solution was
      investigated by potentiometric pH titrations. The results indicate that the main
      species are two ternary complexes at the pH range 7.0-7.4. Biochemical assays
      demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors
      of PTP1B with IC(50) values in the range of 62-597nM, approximately 3-10 fold
      weaker in potency than those of similar mixed-ligand oxovanadium(IV) complexes of
      salicylidene anthranilic acid (SAA) derivative with polypyridyl ligands, except
      complex 8, which exhibits comparable or better inhibition activity than those of
      the mixed-ligand oxovanadium(IV) complexes of SAA derivative with polypyridyl
      ligands. The results demonstrate that the structures of vanadium complexes
      influence the PTP1B inhibition activity. Kinetics assays reveal that complex 2
      inhibits PTP1B in a competitive manner.

PMID- 21864811
TI  - DNA strand breakage induced by CuII and NiII, in the presence of peptide models
      of histone H2B.
AB  - In the present study we used the plasmid relaxation assay, a very sensitive
      method for detection of DNA strand breaks in vitro, in order to evaluate the role
      of peptide fragments of histone H2B in DNA strand breakage induced by copper and
      nickel. We have found that in the presence of peptides modeling the histone fold
      domain (H2B(32-62) and H2B(63-93)) as well as the N-terminal tail (H2B(1-31)) of
      histone H2B there is an increased DNA damage by Cu(2+)/H(2)O(2) and
      Ni(2+)/H(2)O(2) reaction mixtures. On the contrary, the C-terminal tail (H2B(94
      125)) seems to have a protective role on the attack of ROS species to DNA. We
      have rendered our findings to the interactions of the peptides with DNA, as well
      as with the metal.

PMID- 21864812
TI  - Reference limits for N-terminal-pro-B-type natriuretic peptide in healthy
      individuals (from the Framingham Heart Study).
AB  - N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a commonly measured
      cardiovascular biomarker in ambulatory and hospital settings. Nonetheless, there
      are limited data regarding "normal" ranges for NT-pro-BNP in healthy subjects,
      despite the importance of such information for interpreting natriuretic peptide
      measurements. In this study, a healthy reference sample free of cardiovascular
      disease from the Framingham Heart Study Generation 3 cohort was examined; there
      were 2,285 subjects (mean age 38 years, 56% women). Plasma NT-pro-BNP levels were
      measured using the Roche Diagnostics Elecsys 2010 assay, and reference values
      (2.5th, 50th, and 97.5th quantiles) were determined using empiric and quantile
      regression methods. Gender, age, blood pressure, and body mass index accounted
      for approximately 33% of the interindividual variability in NT-pro-BNP in the
      reference sample. NT-pro-BNP values were substantially higher in women compared
      to men at every age, and levels increased with increasing age for both genders.
      Using quantile regression, the upper reference values (97.5th quantile) for NT
      pro-BNP were 42.5 to 106.4 pg/ml in men (depending on age) and 111.0 to 215.9
      pg/ml in women. Intraindividual variability was assessed in an additional 12
      healthy subjects, who had serial NT-pro-BNP measurements over 1 month. Intraclass
      correlation was 0.85, indicating that most of the variability in NT-pro-BNP
      concentrations was among rather than within subjects. However, the reference
      change value was 100%, suggesting that small proportional differences in NT-pro
      BNP could be attributable to analytic variability. In conclusion, the reference
      limits obtained from this large, healthy, community-based sample may aid in the
      evaluation of NT-pro-BNP concentrations measured for clinical and research
      purposes.

PMID- 21864813
TI  - Patency of paclitaxel-eluting versus bare metal stents long term after
      implantation in acute ST-segment elevation myocardial infarction.
AB  - Drug-eluting stents effectively inhibit neointimal hyperplasia within the first
      year, thereby reducing the need for repeat revascularization. However, a delayed
      pattern of restenosis might be more prominent in drug-eluting stents compared to
      bare metal stents (BMSs). The extent of restenosis of paclitaxel-eluting stents
      (PESs) long term after implantation in acute ST-segment elevation myocardial
      infarction is currently unknown. The present study was designed to evaluate very
      late luminal loss (VLLL) of PESs used in ST-segment elevation myocardial
      infarction compared to BMSs. A total of 116 patients (61 with PESs and 55 with
      BMSs) initially included in the Paclitaxel Eluting Stent Versus Conventional
      Stent in ST-segment Elevation Myocardial Infarction (PASSION) trial and who were
      free from previous lesion failure underwent angiographic follow-up. Off-line
      quantitative coronary analysis of the angiogram immediately after stent
      implantation and at follow-up was performed. The primary end point was VLLL
      within the stent. The presence of binary restenosis was defined as diameter
      stenosis >50% as a secondary end point. The mean interval between stent
      implantation and follow-up was 4.1 +/- 0.5 years in both stent groups. In-stent
      VLLL was 0.12 mm (interquartile range -0.03 to 0.42) in the PES group versus 0.30
      mm (interquartile range 0.08 to 0.69) in the BMS group (p = 0.011). In-segment
      binary restenosis was found in 4 patients (6.6%) with a PES and 6 patients
      (10.9%) with a BMS (p = 0.40). In conclusion, angiographic follow-up 4 years
      after implantation in ST-segment elevation myocardial infarction showed that in
      patients prospectively randomized to PESs or BMSs, VLLL was low in both stent
      groups. PESs were associated with lower VLLL than BMSs, and the observed rate of
      binary restenosis was not significantly different between the 2 stent groups.

PMID- 21864814
TI  - Gender differences of atrial and ventricular remodeling and autonomic tone in
      nonelite athletes.
AB  - Veteran endurance athletes have an increased risk of developing atrial
      fibrillation (AF), with a striking male predominance. We hypothesized that male
      athletes were more prone to atrial and ventricular remodeling and investigated
      the signal-averaged P wave and factors that promote the occurrence of AF.
      Nonelite athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10
      mile race, were invited. Of the 873 marathon and nonmarathon runners who were
      willing to participate, 68 female and 70 male athletes were randomly selected.
      The runners with cardiovascular disease or elevated blood pressure (>140/90 mm
      Hg) were excluded. Thus, 121 athletes were entered into the final analysis. Their
      mean age was 42 +/- 7 years. No gender differences were found for age, lifetime
      training hours, or race time. The male athletes had a significantly longer signal
      averaged P-wave duration (136 +/- 12 vs 122 +/- 10 ms; p <0.001). The left atrial
      volume was larger in the male athletes (56 +/- 13 vs 49 +/- 10 ml; p = 0.001),
      while left atrial volume index showed no differences (29 +/- 7 vs 30 +/- 6 ml/m2;
      p = 0.332). In male athletes, the left ventricular mass index (107 +/- 17 vs 86
      +/- 16 g/m2; p <0.001) and relative wall thickness (0.44 +/- 0.06 vs 0.41 +/-
      0.07; p = 0.004) were greater. No differences were found in the left ventricular
      ejection fraction (63 +/- 4% vs 66 +/- 6%; p = 0.112) and mitral annular tissue
      Doppler e' velocity (10.9 +/- 1.5 vs 10.6 +/- 1.5 cm/s; p = 0.187). However, the
      tissue Doppler a' velocity was higher (8.7 +/- 1.2 vs 7.6 +/- 1.3 cm/s; p <
      0.001) in the male athletes. Male athletes had a higher systolic blood pressure
      at rest (123 +/- 9 vs 110 +/- 11 mm Hg; p < 0.001) and at peak exercise (180 +/-
      15 vs 169 +/- 19 mm Hg; p = 0.001). In the frequency domain analysis of heart
      rate variability, the sympatho-vagal balance, represented by the low/high
      frequency power ratio, was significantly greater in male athletes (5.8 +/- 2.8 vs
      3.9 +/- 1.9; p < 0.001). Four athletes (3.3%) had at least one documented episode
      of paroxysmal AF, all were men (p = 0.042). In conclusion, for a comparable
      amount of training and performance, male athletes showed a more pronounced atrial
      remodeling, a concentric type of ventricular remodeling, and an altered diastolic
      function. A higher blood pressure at rest and during exercise and a higher
      sympathetic tone might be causal. The altered left atrial substrate might
      facilitate the occurrence of AF.

PMID- 21864815
TI  - Meta-analysis of monotherapy versus combination therapy for pulmonary arterial
      hypertension.
AB  - Previous studies comparing combination therapy (CT) of pulmonary vasodilators to
      monotherapy (MT) in patients with pulmonary arterial hypertension (PAH) report
      conflicting results as to whether CT is more efficacious than MT. We
      systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for
      randomized controlled trials comparing CT to MT for patients with PAH. Data were
      pooled using the DerSimonian-Laird random-effects model. Six randomized
      controlled trials including 729 patients met our inclusion criteria. Follow-up
      ranged from 12 to 16 weeks. Compared to MT, CT resulted in a modest increase in 6
      minute walk distance at the end of follow-up (weighted mean difference 25.2 m,
      95% confidence interval [CI] 13.3 to 37.2). CT did not decrease mortality (risk
      ratio [RR] 0.42, 95% CI 0.08 to 2.25), admissions for worsening PAH (RR 0.72, 95%
      CI 0.36 to 1.44), or escalation of therapy (RR 0.36, 95% CI 0.09 to 1.39) and did
      not improve New York Heart Association functional class (RR 1.32, 95% CI 0.38 to
      4.5) compared to MT. Incidence of study-drug discontinuation was similar between
      groups (RR 0.89, 95% CI 0.53 to 1.48). CT did not decrease the combined end point
      of mortality, admission for worsening PAH, lung transplantation, or escalation of
      PAH therapy (RR 0.42, 95% CI 0.17 to 1.04). In conclusion, this meta-analysis
      suggests that in PAH CT does not offer an advantage over MT apart from modestly
      increasing exercise capacity. However, given the paucity of good-quality data,
      more studies are required to define the efficacy of CT in this population before
      establishing final guidelines.

PMID- 21864816
TI  - Impact of smoking on outcomes of patients with ST-segment elevation myocardial
      infarction (from the HORIZONS-AMI Trial).
AB  - We assessed the impact of smoking on outcomes in patients with ST-segment
      elevation myocardial infarction treated with primary percutaneous coronary
      intervention using alternative antithrombotic regimens and stent types. In the
      HORIZONS-AMI trial 3,602 patients were randomly assigned to unfractionated
      heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) or bivalirudin alone
      and paclitaxel-eluting stents or bare-metal stents. Compared to nonsmokers,
      smokers had significantly lower rates of mortality and major bleeding at 30 days
      and at 1 year; however, the differences were no longer significant after
      covariate adjustment. Smoking was associated with increased rates of
      definite/probable stent thrombosis (ST) at 1 year (adjusted RR 1.99, 95%
      confidence interval 1.28 to 3.10) mainly because of a higher rate of late ST
      after paclitaxel-eluting stent implantation (1.9% vs 0.4%, p = 0.0006). In
      smokers bivalirudin monotherapy compared to UFH plus a GPI was associated with
      lower mortality at 30 days (0.5% vs 2.2%, p = 0.002) and at 1 year (1.8% vs 4.0%,
      p = 0.008). No decrease in mortality was seen with bivalirudin in nonsmokers.
      Major bleeding was significantly decreased with bivalirudin regardless of smoking
      status (smokers 3.7% vs 8.9%, p <0.0001; nonsmokers 6.5% vs 9.6%, p = 0.01). In
      conclusion, in patients with ST-segment elevation myocardial infarction treated
      with primary percutaneous coronary intervention, smoking is an independent
      predictor of definite/probable ST at 1 year. Bivalirudin monotherapy compared to
      UFH plus a GPI decreased major bleeding regardless of smoking status but may have
      different effects on individual components of ischemic events.

PMID- 21864817
TI  - Outcome of sirolimus-eluting versus zotarolimus-eluting coronary stent
      implantation in patients with and without diabetes mellitus (a SORT OUT III
      Substudy).
AB  - Diabetes is associated with an increased risk of major adverse cardiac events
      after percutaneous coronary intervention. We compared clinical outcomes in
      patients with and without diabetes mellitus treated with the second-generation
      Endeavor zotarolimus-eluting stent (ZES) or the first-generation Cypher Select+
      sirolimus-eluting stent (SES). We randomized 2,332 patients to treatment with
      ZESs (n = 1,162, n = 169 diabetics) or SESs (n = 1,170, n = 168 diabetics) and
      followed them for 18 months. Randomization was stratified by presence/absence of
      diabetes. The primary end point was major adverse cardiac events defined as a
      composite of cardiac death, myocardial infarction, or target vessel
      revascularization. Secondary end points included these individual end points plus
      all-cause mortality and target lesion revascularization. In diabetic patients,
      use of ZES compared to SES was associated with an increased risk of major adverse
      cardiac events (18.3% vs 4.8%, hazard ratio 4.05, 95% confidence interval 1.86 to
      8.82), myocardial infarction (4.7% vs 0.6%, hazard ratio 8.09, 95% confidence
      interval 1.01 to 64.7), target vessel revascularization (14.2% vs 3.0%, hazard
      ratio 4.99, 95% confidence interval 1.90 to 13.1), and target lesion
      revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59
      to 47.1). In patients without diabetes differences in absolute risk decrease were
      smaller but similarly favored SES. In conclusion, implantation of ZESs compared
      to SESs is associated with a considerable increased risk of adverse events in
      patients with diabetes at 18-month follow-up.

PMID- 21864818
TI  - Relation between left ventricular morphology and reduction in functional mitral
      regurgitation by cardiac resynchronization therapy in patients with idiopathic
      dilated cardiomyopathy.
AB  - The presence of functional mitral regurgitation (MR) is considered a significant
      risk factor for poor clinical prognosis in patients with idiopathic dilated
      cardiomyopathy (IDC). The objectives of this study were to test the hypothesis
      that not only global but also local left ventricular (LV) remodeling, including
      the position of the papillary muscles, may contribute to the development of MR in
      patients with IDC and wide QRS durations and can be reversed with cardiac
      resynchronization therapy (CRT). Eighty-four subjects were studied, 44 patients
      with IDC who underwent CRT and 40 age- and gender-matched controls. The position
      of the posteromedial papillary muscle was similar in the 2 groups, whereas the
      position of the anterolateral papillary muscle in patients with IDC was displaced
      more posteriorly than in controls. Multivariate analysis revealed that reduction
      in coaptation height (beta = 0.44, p <0.001) and LV dyssynchrony by speckle
      tracking radial strain (beta = 0.303, p <0.01) were independent determinants of
      reduction in MR 5 +/- 2 days after CRT; in contrast, restoration of the position
      of the posteriorly displaced anterolateral papillary muscle (beta = 0.50, p
      <0.001) and the increase in sphericity index (beta = 0.440, p <0.001) were
      identified as independent determinants of reduction in MR 6 +/- 1 months after
      CRT. In conclusion, asymmetric local LV remodeling was observed at baseline, and
      asymmetric local LV reverse remodeling was observed at long-term follow-up after
      CRT in patients with IDC. Furthermore, different parameters contribute to the
      reduction in MR observed at short- and long-term follow-up after CRT.

PMID- 21864819
TI  - Usefulness of serum bilirubin and cardiorespiratory fitness as predictors of
      mortality in men.
AB  - Elevated serum bilirubin has been suggested to reduce the risk for mortality.
      Cardiorespiratory fitness (CRF) has also been reported to have inverse
      association with all-cause and cardiovascular disease (CVD) mortality. The
      association between serum bilirubin, all-cause and CVD mortality, and the effect
      of CRF on the observed association was investigated. A total of 1,279 men aged 30
      to 82 years underwent baseline medical examinations from 1974 to 1997 at the
      Cooper Clinic in Dallas, Texas. During an average of 17 years of follow-up, 698
      men died, with 253 deaths due to CVD (36%). Men in the highest bilirubin
      quartiles had significantly lower risk for all-cause mortality compared to men in
      the lowest quartiles (p for trend = 0.0043), after adjusting for age and
      examination year. This inverse association remained significant after further
      adjustment for known confounders (p for trend = 0.0018). Additional adjustment
      for treadmill time attenuated the association (p for trend = 0.0090). Similar
      patterns of association were observed between serum bilirubin quartiles and CVD
      mortality. CRF was inversely associated with all-cause mortality (p for trend
      <0.0001) after adjusting for age and examination year. This inverse association
      also was observed after further adjusting for known confounders (p for trend =
      0.0004). After additional adjustment for serum bilirubin, the association between
      CRF and all-cause mortality remained significant (p for trend = 0.0012). All
      cause mortality and CVD mortality were significantly lower in men in the moderate
      to high-fitness quartiles in the low- and high-bilirubin groups. In conclusion,
      serum bilirubin level and CRF level were strongly and independently associated
      with all-cause and CVD mortality.

PMID- 21864820
TI  - Evaluation of a rapid, real-time intrapartum group B streptococcus assay.
AB  - OBJECTIVE: We sought to evaluate an intrapartum nucleic acid amplification test
      (NAAT) for group B streptococcus (GBS). STUDY DESIGN: This was a prospective
      cohort study of 559 women comparing intrapartum GBS culture with antepartum
      culture and intrapartum NAAT. RESULTS: GBS prevalence was 19.5% by antepartum
      culture and 23.8% by intrapartum culture. Compared with intrapartum culture,
      antepartum culture had 69.2% sensitivity (60.6-76.9%) and 96.0% specificity (93.7
      97.7%). The NAAT demonstrated sensitivity of 90.8% (84.6-95.2%), specificity of
      97.6% (95.6-98.8%), and predictive values >92%. The incidence of discordant
      cultures was 10.4%. Of the women with negative antepartum and positive
      intrapartum cultures, only 1 (2.4%) received intrapartum antibiotics. Compared
      with white women, black (P = .02) and Hispanic (P = .02) women were more likely
      to have discordant cultures. CONCLUSION: This intrapartum NAAT has excellent
      characteristics. It may be superior to antepartum culture for detecting
      intrapartum GBS-allowing more accurate management of laboring mothers and
      reducing neonatal GBS sepsis.

PMID- 21864821
TI  - Impact of morbid obesity on epidural anesthesia complications in labor.
AB  - OBJECTIVE: We sought to determine whether morbid obesity is associated with
      increased maternal hypotension or fetal heart rate (FHR) abnormalities after
      epidural anesthesia placement during labor. STUDY DESIGN: This was a
      retrospective cohort study of women undergoing epidural anesthesia during labor
      at term from April 2008 through July 2010. RESULTS: A total of 125 morbidly obese
      patients were matched for age and race with 125 normal-weight patients. Morbidly
      obese patients had more frequent persistent systolic (16% vs 4%, P = .003) and
      diastolic (49% vs 29%, P = .002) hypotension and more prolonged (16% vs 5%, P =
      .006) and late (26% vs 14%, P = .03) FHR decelerations. Increasing body mass
      index was associated with persistent systolic (odds ratio, 1.06; 95% confidence
      interval, 1.02-1.10) and diastolic (odds ratio, 1.04; 95% confidence interval,
      1.01-1.06) hypotension after controlling for epidural bolus dose and hypertensive
      disorders. CONCLUSION: Morbidly obese women have more hypotension and prolonged
      FHR decelerations following epidural anesthesia during labor at term.

PMID- 21864822
TI  - Discordant twins: diagnosis, evaluation and management.
AB  - Approximately 16% of twin gestations have discordance of at least 20%. We
      identified 14 risk factors for divergent growth that can be categorized as
      maternal, fetal, or placental. Determination of chorionicity and serial
      ultrasound evaluation with a high index of suspicion for divergent growth is
      required for the diagnosis and stratification of risk. The highest reported
      likelihood ratio for detection of discordance was 5.9 during the first trimester
      examination and 6.0 for the second trimester. Although our ability to identify
      discordant twins is limited, once suspected and at viable gestational age, these
      pregnancies should have antepartum testing. Discordant growth alone is not an
      indication for preterm birth. Although there are multiple publications on the
      increased morbidity and mortality rates with discordant growth, there is a
      paucity of reports on how to manage them optimally and deliver them in a timely
      manner.

PMID- 21864823
TI  - Placental cord insertion and birthweight discordance in twin pregnancies: results
      of the national prospective ESPRiT Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of noncentral
      placental cord insertion on birthweight discordance in twins. STUDY DESIGN: We
      performed a multicenter, prospective trial of twin pregnancies. Placental cord
      insertion was documented as central, marginal, or velamentous according to a
      defined protocol. Association of the placental cord insertion site with
      chorionicity, birthweight discordance, and growth restriction were assessed.
      RESULTS: Eight hundred sixteen twin pairs were evaluated; 165 pairs were
      monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher
      rates of marginal (P = .0068) and velamentous (P < .0001) placental cord
      insertion. Noncentral placental cord insertion was more frequent in smaller twins
      of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous
      placental cord insertion in monochorionic twins was associated significantly with
      birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3-9.4) and
      growth restriction (odds ratio, 4; 95% confidence interval, 1.1-14.3).
      CONCLUSION: Noncentral placental cord insertion contributes to birthweight
      discordance in monochorionic twin pregnancies. Sonographic delineation of
      placental cord insertion may be of value in antenatal assessment of twin
      pregnancies.

PMID- 21864824
TI  - A systematic review of severe morbidity in infants born late preterm.
AB  - OBJECTIVE: Late-preterm infants (34 weeks 0/7 days-36 weeks 6/7 days' gestation)
      represent the largest proportion of singleton preterm births. A systematic review
      was performed to access the short- and/or long-term morbidity of late-preterm
      infants. STUDY DESIGN: An electronic search was conducted for cohort studies
      published from January 2000 through July 2010. RESULTS: We identified 22 studies
      studying 29,375,675 infants. Compared with infants born at term, infants born
      late preterm were more likely to suffer poorer short-term outcomes such as
      respiratory distress syndrome (relative risk [RR], 17.3), intraventricular
      hemorrhage (RR, 4.9), and death <28 days (RR, 5.9). Beyond the neonatal period,
      late-preterm infants were more likely to die in the first year (RR, 3.7) and to
      suffer from cerebral palsy (RR, 3.1). CONCLUSION: Although the absolute incidence
      of neonatal mortality and morbidity in infants born late preterm is low, its
      incidence is significantly increased as compared with infants born at term.

PMID- 21864825
TI  - Do adhesions at repeat cesarean delay delivery of the newborn?
AB  - OBJECTIVE: We sought to assess whether the presence and severity of adhesions at
      first repeat cesarean delivery are associated with delayed delivery of the
      newborn. STUDY DESIGN: We conducted secondary analysis of a prospective cohort of
      women undergoing first repeat cesarean. Severity and location of adhesions were
      reported by surgeons immediately postoperatively. We compared adhesion density
      scores with delivery data. RESULTS: Of 145 women analyzed, 92 (63.5%) had
      adhesions and 53 (36.5%) did not. Mean incision to delivery time in women with
      adhesion scores >3 was 19.8 minutes, compared to 15.6 minutes with scores <= 3 (P
      = .04). More women with adhesion scores >3 remained undelivered at 30 minutes
      after incision compared to scores <= 3 (17.9% vs 5.1%; odds ratio, 7.6; 95%
      confidence interval, 1.6-34.5), after controlling for potential confounders.
      CONCLUSION: Among women undergoing first repeat cesarean, severity of adhesions
      may delay delivery of the newborn. Study of techniques to reduce adhesions may be
      warranted to prevent delayed delivery at repeat cesarean.

PMID- 21864826
TI  - Interobserver and intraobserver reliability of the NICHD 3-Tier Fetal Heart Rate
      Interpretation System.
AB  - OBJECTIVE: Our purpose was to test the reliability of the Eunice Kennedy Shriver
      National Institute of Child Health and Human Development (NICHD) 3-Tier Fetal
      Heart Rate (FHR) classification system. STUDY DESIGN: Individual 15- to 20-minute
      FHR segments (n = 154) were independently reviewed without clinical data by 3
      maternal-fetal medicine examiners and classified by NICHD category (I, II, III).
      RESULTS: Interobserver reliability was moderate (kappa 0.45) and varied by NICHD
      category (category I moderate [kappa 0.48], category II moderate [kappa 0.44],
      and category III poor [kappa 0.0]). The intraobserver agreement ranged from
      substantial to perfect (kappa 0.74-1.0). CONCLUSION: Interobserver agreement of 3
      Tier FHR classification System was moderate for NICHD categories I and II.
      Agreement for category III tracings was poor mainly due to lack of agreement
      regarding absent vs minimal variability.

PMID- 21864827
TI  - Evaluation of the choroidal thickness using high-penetration optical coherence
      tomography with long wavelength in highly myopic normal-tension glaucoma.
AB  - PURPOSE: To evaluate the choroidal thickness by high-penetration optical
      coherence tomography (OCT) using long wavelength in highly myopic normal-tension
      glaucoma (NTG). DESIGN: Cross-sectional retrospective study. METHODS:  SETTINGS:
      Institutional. PARTICIPANTS: Twelve eyes from 8 patients under 45 years old,
      diagnosed as NTG without any other ocular diseases, spherical equivalent
      refractive error between -6 and -12 diopters, and axial length greater than 26.5
      mm; and 12 eyes of matched healthy volunteers. INTERVENTION: Choroid was imaged
      with prototype high-penetration OCT and its thickness was measured. MAIN OUTCOME
      MEASURES: Choroidal thickness at the fovea and 5 locations: 2 mm superior,
      temporal, and inferior to the center of the optic nerve head, and 2 mm superior
      (superotemporal) and 2 mm inferior (inferotemporal) to the temporal location.
      RESULTS: Overall, the choroidal thickness in the NTG group was approximately 50%
      that in controls. Mean choroidal thickness in the NTG group was significantly
      thinner in the control group at the fovea (166 vs 276 MUm, P < .001), superior
      (172 vs 241 MUm, P < 0.05), superotemporal (161 vs 244 MUm, P < .01), temporal
      (110 vs 161 MUm, P < .01), and inferotemporal (115 vs 159 MUm, P < .05) to the
      optic nerve head. Stepwise analysis disclosed that the foveal choroidal thickness
      is the most influential factor on the occurrence of NTG (P < .0001, R(2) = 0.4).
      CONCLUSIONS: Choroidal thickness in highly myopic NTG is significantly thinner
      than in controls, at least in some specific locations. Choroidal thinning is
      somehow related with highly myopic NTG and may be a useful diagnostic parameter
      for myopic NTG.

PMID- 21864828
TI  - Keratocyte density 3 months, 15 months, and 3 years after corneal surface
      ablation with mitomycin C.
AB  - PURPOSE: To study the effects of surface ablation with mitomycin C (MMC) on
      keratocyte population. DESIGN: Prospective, nonrandomized, interventional,
      comparative case series. METHODS: Thirty two eyes treated with surface ablation
      with 0.02% MMC were compared with nontreated eyes at Vissum Santa Hortensia,
      Madrid, Spain. Keratocyte density was measured with the Heidelberg Retina
      Tomograph II (Rostock Cornea Module) 3, 15, and 36 to 42 months after the surgery
      in the anterior, mid, and posterior stroma, and compared with control eyes.
      RESULTS: Three months postoperatively, we found a lower stromal bed density
      compared to controls (16 993 +/- 8001 vs 29 660 +/- 5904 cells/mm(3), P = .0001),
      while there was a significantly higher cell density in the mid (30 783 +/- 9300
      vs 18 505 +/- 1996 cells/mm(3), P = .0001) and deep stroma (30 268 +/- 8321 vs 18
      438 +/- 2139 cells/mm(3), P = .0001). Three years after the surgery, the
      cellularity in the stromal bed had not significantly changed from the 3-month
      follow-up, but the density in the mid (18 889 +/- 3474 cells/mm(3)) and posterior
      stroma (18 992 +/- 3402 cells/mm(3)) had decreased to show no difference from
      controls. The mean cell density between the anterior, mid, and posterior stroma
      was not significantly different from controls 15 months and 3 years after the
      surgery. CONCLUSION: Our study suggests that there is a reorganization of the
      stromal cell population soon after surface ablation with MMC, with a decrease in
      the stromal bed compensated initially with an increase in the mid and posterior
      stroma. Corneal cellularity tends to normalize over time, and 3 years
      postoperatively the mean cell density throughout the cornea seems to maintain
      normal values.

PMID- 21864829
TI  - Effects of early anticoagulation on the degree of thrombosis After repair of
      acute DeBakey type I aortic dissection.
AB  - BACKGROUND: The degree of false lumen thrombosis after surgical repair of acute
      DeBakey type I aortic dissection can predict long-term outcomes. However, there
      are currently no evidence-based recommendations for anticoagulation. We analyzed
      the effect of early anticoagulation on the residual false lumen and long-term
      outcomes. METHODS: This was a retrospective observational study of 136 patients
      with acute DeBakey type I aortic dissection who underwent surgical repair between
      1997 and 2007. We assessed the effect of early anticoagulation on the degree of
      thrombosis of the false lumen, segmental growth rates, repeat distal procedures,
      and long-term survival. RESULTS: Among the 136 patients who underwent operations,
      imaging data in 103 were sufficient for analyzing the degree of thrombosis of the
      false lumen. Of those, 56 (54%) received anticoagulation therapy immediately
      postoperatively. The early-anticoagulation group had a higher proportion of
      completely patent false lumens and lower partial thrombosis than the no
      anticoagulation group. Mean segmental aortic growth rate was significantly lower
      in the early-anticoagulation group than in the no-anticoagulation group (2.9 +/-
      1.3 and 4.5 +/- 2.8 mm/year, p = 0.0184). Overall survival and aorta-related
      repeat procedure-free survival were significantly better with early
      anticoagulation than with no anticoagulation (p < 0.05). CONCLUSIONS: Early
      anticoagulation after surgical repair of acute DeBakey type I aortic dissection
      might have a favorable effect on the onset or extension of thrombosis, aortic
      growth rate, the need for repeat distal procedures, overall survival, and
      thrombosis-related complications during long-term follow-up.

PMID- 21864830
TI  - Acceptance and commitment therapy versus tinnitus retraining therapy in the
      treatment of tinnitus: a randomised controlled trial.
AB  - The study compared the effects of Acceptance and Commitment Therapy (ACT) with
      Tinnitus Retraining Therapy (TRT) on tinnitus impact in a randomised controlled
      trial. Sixty-four normal hearing subjects with tinnitus were randomised to one of
      the active treatments or a wait-list control (WLC). The ACT treatment consisted
      of 10 weekly 60 min sessions. The TRT treatment consisted of one 150 min session,
      one 30 min follow-up and continued daily use of wearable sound generators for a
      recommended period of at least 8h/day for 18 months. Assessments were made at
      baseline, 10 weeks, 6 months and 18 months. At 10 weeks, results showed a
      superior effect of ACT in comparison with the WLC regarding tinnitus impact
      (Cohen's d=1.04), problems with sleep and anxiety. The results were mediated by
      tinnitus acceptance. A comparison between the active treatments, including all
      assessment points, revealed significant differences in favour of ACT regarding
      tinnitus impact (Cohen's d=0.75) and problems with sleep. At 6 months, reliable
      improvement on the main outcome measure was found for 54.5% in the ACT condition
      and 20% in the TRT condition. The results suggest that ACT can reduce tinnitus
      distress and impact in a group of normal hearing tinnitus patients.

PMID- 21864831
TI  - The alterations of oligodendrocyte, myelin in corpus callosum, and cognitive
      dysfunction following chronic cerebral ischemia in rats.
AB  - Although the white matter lesions, so called leuko-araiosis, often seen in
      elderly people have been gaining attention due to their association with
      cognitive dysfunction (CD) and high risk of incident stroke, the pathological
      significance of these lesions still remains controversial. Therefore, in the
      present study, we investigated the alterations in oligodendrocytes (OLG),
      including oligodendrocytes progenitor cells (OPCs), myelin, and CD following
      chronic cerebral ischemia in rats. SD rats were subjected to bilateral common
      carotid artery occlusion. Immunohistochemical staining was performed at 2, 4, 6,
      8, and 12weeks after the induction of ischemia with anti-NG2 (OPCs), anti-GST-pi
      (OLG), and anti-MBP antibodies in paramedian corpus callosum (CC). CD was
      assessed by the Morris water maze test. There was a significant decrease in the
      number of GST-pi positive cells at 2weeks after the start of ischemia compared
      with that seen in the sham group. There was a significant increase of the number
      of NG2 positive cells at 4weeks in the ischemia group compared with the sham
      group. In the ischemic group, the amount of MBP was observed to have decreased
      significantly at each time point compared with the sham group. CD was observed in
      the ischemic group than that in the sham group at all time points. Our results
      indicate that remyelination is strongly correlated with the recovery of cognitive
      dysfunction following chronic cerebral ischemia.

PMID- 21864832
TI  - Synthesis and antibacterial evaluation of a series of oligorhamnoside
      derivatives.
AB  - A series of novel oligorhamnoside derivatives (1-10) and naturally occurring
      cleistrioside-5 were synthesized and evaluated for their in vitro antibacterial
      activities. Among them, dirhamnoside derivative 7 and cleistrioside-5 displayed
      similar antibacterial profiles and exhibited moderate to good inhibitory
      activities on bacterial growth against a panel of Gram-positive bacteria (MICs <=
      4-32 MUg/mL). The results revealed that these two compounds showed selectivity
      towards bacterial species strictly, without being affected by the antibiotic
      resistant/susceptible properties of one species, which suggested that they might
      have the potential to avoid antibiotic cross-resistance. In addition, the
      preliminary SARs of this type of oligorhamnoside derivatives on the antibacterial
      activities were determined.

PMID- 21864833
TI  - Synthesis of various 5-alkoxymethyluracil analogues and structure-cytotoxic
      activity relationship study.
AB  - A number of 5-alkoxymethyluracil analogues were synthesized to evaluate their
      cytotoxic activity. 5-Alkoxymethyluracil derivatives 1 were prepared via known
      nucleophilic substitution of 5-chloromethyluracil 5 and subsequently transformed
      to their corresponding nucleosides 2. All prepared compounds were submitted to
      cytotoxic activity testing against drug sensitive and drug resistant leukaemia
      cells and solid tumour derived cell lines. In addition, the cytotoxic activity of
      5-alkoxymethyluracil analogues 1 and 2 was compared with the previously published
      5-[alkoxy(4-nitrophenyl)methyl]uracil analogues 3 and 4. Extensive structure
      cytotoxic activity relationship studies are reported.

PMID- 21864834
TI  - Prospective investigation of a PTSD personality typology among individuals with
      personality disorders.
AB  - This study investigated the replicability of a previously proposed personality
      typology of posttraumatic stress disorder (PTSD, and explored stability of
      cluster membership over a 6-month period. Participants with current PTSD (n =
      156) were drawn from the Collaborative Longitudinal Personality Disorders Study
      (CLPS). The CLPS project tracked a large sample of individuals who met criteria
      for 1 of 4 target diagnoses (borderline, schizotypal, avoidant, and obsessive
      compulsive) and a contrast group of individuals who met criteria for depression
      but no personality disorder. A cluster analysis using scales from the Schedule of
      Nonadaptive and Adaptive Personality yielded 3 clusters: "internalizing,"
      "externalizing," and "low pathology." Using K-means cluster analysis, the results
      did not replicate previous work. Using Ward's method, the hypothesized 3-cluster
      structure was confirmed at baseline but did not demonstrate temporal stability at
      6 months.

PMID- 21864835
TI  - Bilateral self-enucleation in acute transient psychotic disorder: the influence
      of sociocultural factors on psychopathology.
AB  - Self-inflicted eye injuries are rare but a devastating consequence of a serious
      mental disorder. Bilateral self-enucleation also known as oedipism has been
      documented in ancient texts and myths. Various biologic, psychologic, and social
      theories have been put forward to explain this rare phenomenon. In this report,
      we describe a case of oedipism, which highlights the influence of sociocultural
      factors on the psychopathology in acute transient psychotic disorder.

PMID- 21864836
TI  - Learning to associate novel words with motor actions: language-induced motor
      activity following short training.
AB  - Action words referring to face, arm or leg actions activate areas along the motor
      strip that also control the planning and execution of the actions specified by
      the words. This electroencephalogram (EEG) study aimed to test the learning
      profile of this language-induced motor activity. Participants were trained to
      associate novel verbal stimuli to videos of object-oriented hand and arm
      movements or animated visual images on two consecutive days. Each training
      session was preceded and followed by a test-session with isolated videos and
      verbal stimuli. We measured motor-related brain activity (reflected by a
      desynchronization in the MU frequency bands; 8-12 Hz range) localized at centro
      parietal and fronto-central electrodes. We compared activity from viewing the
      videos to activity resulting from processing the language stimuli only. At centro
      parietal electrodes, stable action-related MU suppression was observed during
      viewing of videos in each test-session of the two days. For processing of verbal
      stimuli associated with motor actions, a similar pattern of activity was evident
      only in the second test-session of Day 1. Over the fronto-central regions, MU
      suppression was observed in the second test-session of Day 2 for the videos and
      in the second test-session of Day 1 for the verbal stimuli. Whereas the centro
      parietal MU suppression can be attributed to motor events actually experienced
      during training, the fronto-central MU suppression seems to serve as a
      convergence zone that mediates underspecified motor information. Consequently,
      sensory-motor reactivations through which concepts are comprehended seem to
      differ in neural dynamics from those implicated in their acquisition.

PMID- 21864837
TI  - Cognitive deficits from a cerebellar tumour: a historical case report from
      Luria's Laboratory.
AB  - In 1964 an original case report from A.R. Luria's Laboratory of Neuropsychology
      was published in Cortex, being one of the first to draw a link between cerebellum
      and cognition, by highlighting the manifestation of 'pseudo-frontal' symptoms
      resulting from a cerebellar tumour. The findings of Luria and his team seem more
      consistent with modern views about cerebellar interactions with the frontal lobe
      and its contributions to behaviour than the views prevalent at the time of
      publication. The paper was originally submitted in Russian, and translated into
      Italian for its publication by Cortex. However, Cortex did not preserve the
      original manuscript in Russian. With the passage of time, and available only to
      the Italian readership, this case report inevitably fell into obscurity. Hence,
      we present a translation in English based on the published Italian version of the
      manuscript and discuss it in the context of Luria's general thinking about
      information processing in the brain and our current understanding of cortico
      cerebellar system. The publication of this article gives readers an opportunity
      to consider the substantial influence of Soviet neuropsychology on the field
      internationally under Luria's leadership in the 1960s. It also shows that time is
      the best judge of ones scientific endeavours, and what may seem implausible today
      might prove to be valid and worthy of exploration tomorrow.

PMID- 21864838
TI  - Exposure to airborne metals and particulate matter and risk for youth adjudicated
      for criminal activity.
AB  - Antisocial behavior is a product of multiple interacting sociohereditary
      variables, yet there is increasing evidence that metal exposure, particularly,
      manganese and lead, play a role in its epigenesis. Other metals, such as arsenic,
      cadmium, chromium, and mercury, and exposure to traffic-related air pollution,
      such as fine particulate matter (<=2.5 MUm) have been associated with
      neurological deficits, yet largely unexplored with respect to their relationship
      with delinquent behavior. The purpose of this study is to evaluate the ecological
      relationship between county-wide reported airborne emissions of air metals,
      particulate matter, and youth adjudicated for criminal activity. Metal exposure
      data were collected from the Environmental Protection Agency AirData. Population
      statistics were obtained from the United States Census 2000 and adjudication data
      was obtained from the Courts of Common Pleases from each Ohio County. Simple
      correlations were calculated with the percentage of adjudications, all
      covariates, and estimated metal air emissions. Separate negative binomial
      regression models for each pollutant were used to provide an estimated risk ratio
      of pollutant emissions on the risk of adjudication for all Ohio counties
      adjusting for urban-rural residence, percentage of African Americans, median
      family income, percentage of family below poverty, percentage of high school
      graduation in 25 years and older populations, and population density. Metal
      emissions and PM in 1999 were all correlated with adjudication rate (2003-2005
      average). Metal emissions were associated with slightly higher risk of
      adjudication, with about 3-4% increased risk per natural log unit of metal
      emission except chromium. The associations achieved statistical significance for
      manganese and mercury. The particulate matter<=2.5 and <=10 MUm emissions had a
      higher risk estimate, with 12% and 19% increase per natural log unit emission,
      respectively, and also achieved statistical significance. In summary, airborne
      exposure to manganese, mercury, and particulate matter are associated with
      increased risk of adjudication. Causality cannot be proven in observational
      studies such as this one, but the association warrants further examination in
      other research studies. Comprehensive epidemiologic investigations of metal
      exposure in pediatric populations should include social health outcomes,
      including measures of delinquent or criminal activity. Furthermore, the influence
      of metals on the neurotoxic pathway leading to delinquent activity should be
      further explored.

PMID- 21864839
TI  - Fecundity and sex ratio of offspring in an infertile cohort.
AB  - OBJECTIVE: To determine whether male and female subfecundity is associated with
      the gender ratio. DESIGN: Retrospective cohort study. SETTING: Reproductive
      endocrinology clinics in California. PATIENT(S): A cohort of 30,448 women who
      sought infertility treatment or evaluation in California between 1990 and 1998
      was identified. A fertile comparison group was assembled after matching data from
      vital statistics records. INTERVENTION(S): Not applicable. MAIN OUTCOME
      MEASURE(S): Multivariate logistic regression was used to determine the odds of a
      male birth based on fertility status. RESULT(S): We identified 5,293 infertile
      women and 6,730 fertile matched women in the live-birth and fetal death records.
      There were 6,178 children born to women evaluated and/or treated for infertility,
      compared with 9,131 born to fertile women, for a total of 15,309 births. There
      was no significant difference in the secondary sex ratio between births in the
      infertile cohort and the fertile cohort or on the basis of male factor
      infertility versus female factor infertility. After controlling for confounding
      factors, there was no difference in sex ratio based on the use of advanced
      reproductive technologies, duration of infertility treatment, or the type of
      infertility. CONCLUSION(S): This study found no statistical evidence to support
      an association between infertility and secondary sex ratio.

PMID- 21864841
TI  - Heterogeneous response of traction force at focal adhesions of vascular smooth
      muscle cells subjected to macroscopic stretch on a micropillar substrate.
AB  - Traction force generated at focal adhesions (FAs) of cells plays an essential
      role in regulating cellular functions. However, little is known about how the
      traction force at each FA changes during cell stretching. Here we investigated
      dynamic changes in traction force at FAs during macroscopic stretching of porcine
      aortic smooth muscle cells (SMCs) cultured on elastic micropillar substrates.
      SMCs were cultured on polydimethylsiloxane (PDMS)-based substrates with a
      micropillar array, and stretched approximately in the direction of their major
      axis and then released by stretching and relaxing the substrates. This stretch
      release cycle was repeated twice with cell strain rates of 0.3%/15s up to a 3%
      strain, and the deflection of the PDMS micropillars was measured simultaneously
      to obtain the traction force at each FA F, total force in the cell's major axis
      direction F(all), and whole-cell strain epsilon(cell). Traction forces of SMCs
      during stretching varied widely with location: their changes at some pillars
      synchronized well with the applied strain epsilon(cell), but others did not
      synchronized. Whole-cell stiffness estimated as the slope of the loading limb of
      the F(all)-epsilon(cell) curves was ~10nN/%, which was the same order of
      magnitude of the reported stiffness of cultured SMCs obtained in a tensile test.
      Interestingly, F(all) at a zero-strain state (pretension at the whole-cell level)
      actively increased in some cells following the loading/unloading process, as did
      whole-cell stiffness. Such a change did not occur in cultured SMCs in the tensile
      test in which cells were held with a pair of micropipettes coated with
      nonspecific adhesive. These results indicate that SMCs showed a myogenic response
      when stretched through their multiple FAs, but not through nonspecific adhesions
      on their membrane. SMCs may behave differently depending on the sites through
      which they are stretched.

PMID- 21864840
TI  - Altered osteogenic commitment of human mesenchymal stem cells by ERM protein
      dependent modulation of cellular biomechanics.
AB  - Cellular mechanics is known to play an important role in many cellular functions
      including adhesion, migration, proliferation, and differentiation. Human
      mesenchymal stem cells (hMSCs) demonstrate unique mechanical properties distinct
      from fully differentiated cells. This observation suggests that the stem cell
      mechanics may be modulated to regulate the hMSCs' lineage commitment.
      Specifically, ERM (ezrin, radixin, moesin) proteins are known to mediate the
      membrane-cytoskeleton adhesion, cell elasticity, actin cytoskeleton organization,
      and therefore could serve as potential targets for modulation of the cellular
      mechanics. Combining silencing RNA, atomic force microscopy, and laser optical
      tweezers, the role of the ERM proteins involved in the regulation of stem cell
      biomechanics and osteogenic differentiation was quantitatively determined.
      Transient ERM knockdown by RNAi causes disassembly of actin stress fibers and
      focal adhesions, a decrease in the cell stiffness, and membrane separation from
      the cytoskeleton. The silencing RNA treatment not only induced mechanical changes
      in stem cells but impaired biochemically-directed osteogenic differentiation. The
      intact actin cytoskeleton and focal adhesions of hMSCs appear critical for the
      osteogenic induction. Thus, ERM knockdown modulates the dynamics of cell
      mechanical changes during hMSC differentiation and regulates the expression of
      tissue specific molecular markers. These findings are of particular interest for
      modulation of the cellular biomechanics to control hMSCs' activities and fate in
      tissue engineering, regenerative medicine, and other stem cell-based therapeutic
      applications.

PMID- 21864842
TI  - Chiral separation of agricultural fungicides.
AB  - Fungicides are very important and diverse environmental and agricultural concern
      species. Their determination in commercial formulations or environmental
      matrices, requires highly efficient, selective and sensitive methods. A
      significant number of these chemicals are chiral with the activity residing
      usually in one of the enantiomers. The different toxicological and degradation
      behavior observed in many cases for fungicide enantiomers, results in the need to
      investigate them separately. For this purpose, separation techniques such as GC,
      HPLC, supercritical fluid chromatography (SFC) and CE have widely been employed
      although, at present, HPLC still dominates chromatographic chiral analysis of
      fungicides. This review covers the literature concerning the enantiomeric
      separation of fungicides usually employed in agriculture grouping the chiral
      separation methodologies developed for their analysis in environmental,
      biological, and food samples.

PMID- 21864843
TI  - Removal of methyl orange from aqueous solution using bentonite-supported
      nanoscale zero-valent iron.
AB  - Zero-valent iron (ZVI) nanoparticles tend to agglomerate, resulting in a
      significant loss in reactivity. To address this issue, synthesized bentonite
      supported nanoscale zero-valent iron (B-nZVI) was used to remove azo dye methyl
      orange (MO) in aqueous solution. Batch experiments show that various parameters,
      such as pH, initial concentration of MO, dosage, and temperature, were affected
      by the removal of MO. Scanning electron microscopy (SEM) confirmed that B-nZVI
      increased their reactivity and a decrease occurred in the aggregation of iron
      nanoparticles for the presence of bentonite (B). Using B-nZVI, 79.46% of MO was
      removed, whereas only 40.03% when using nZVI after reacting for 10 min with an
      initial MO concentration of 100 mg/L (pH=6.5). Furthermore, after B-nZVI reacted
      to MO, XRD indicated that iron oxides were formed. FTIR showed that no new bands
      appeared, and UV-vis demonstrated that the absorption peak of MO was degraded.
      Kinetics studies showed that the degradation of MO fitted well to the pseudo
      first-order model. A degradation mechanism is proposed, including the following:
      oxidation of iron, adsorption of MO to B-nZVI, formation of Fe(II)-dye complex,
      and cleavage of azo bond. Finally, the removal rate of MO from actual wastewater
      was 99.75% when utilizing B-nZVI.

PMID- 21864844
TI  - Effect of deposition parameters on the wettability and microstructure of
      superhydrophobic films with hierarchical micro-nano structures.
AB  - Superhydrophobic films with hierarchical micro-nano structures were deposited on
      glass substrates by solution immersion method from a solution containing cobalt
      chloride, urea and cetyl trimethyl ammonium bromide (CTAB). Subsequently the
      films were hydrophobized with a low surface energy material like octadecanoic
      acid under ambient conditions resulting in superhydrophobic surfaces with water
      contact angle (WCA) of about 168 degrees  and contact angle hysteresis of 1
      degrees . The effect of deposition parameters such as solution composition,
      temperature, deposition time and alkanoic acid treatment on surface morphology
      and wettability of the films was studied. Mechanism of formation of cobalt
      chloride carbonate hydroxide film is discussed. Addition of CTAB to the solution
      resulted in a change in the surface morphology of the deposited films with flower
      like structures. The wettability of films obtained under different process
      conditions was correlated to surface roughness using Wenzel and Cassie models.

PMID- 21864845
TI  - Melanophoromas and iridophoromas in reptiles.
AB  - Chromatophoromas are tumours of pigment-producing cells of the skin and are
      rarely reported in reptiles. These tumours are subclassified on the basis of the
      type of pigment. The present study characterizes chromatophoromas arising in 26
      reptiles, including six snakes, 19 lizards and a tortoise. These include the
      first reports of melanophoromas in a yellow anaconda (Eunectes notaeus), pigmy
      rattlesnake (Sistrurus spp.), southern water snake (Nerodia fasciata), veiled
      chameleon (Chamaeleo calyptratus) and leopard gecko (Eublepharis macularius); the
      first reports of benign iridophoromas in a savannah monitor (Varanus
      exanthematicus), veiled chameleon and bearded dragon (Pogona vitticeps); and the
      first description of a malignant iridophoroma in a bearded dragon. Additionally,
      in three bearded dragons a 'mucinous' type of melanophoroma is described for the
      first time. Chromatophoromas generally arose from the skin of the body and head
      and ranged in size from 0.2 to 2.0cm in diameter. In six cases the animals were
      humanely destroyed immediately after diagnosis. Three further animals were
      humanely destroyed following recurrence of their tumour. Six of these nine
      reptiles had visceral metastases. Grossly, melanophoromas (n=20) were grey or
      black, while iridophoromas (n=6) were white in colour. Microscopically, most of
      the tumours were composed of spindle cells with varying pigmentation and 0-2
      mitoses per 10 high power fields. Six of the 20 melanophoromas were classified as
      malignant due to the presence of intravascular tumour cells, visceral metastases,
      high pleomorphism and/or mitotic figures. Five of the six iridophoromas were
      classified as benign and the one malignant tumour was defined by the presence of
      intravascular tumour cells and visceral metastases. Immunohistochemically, melan
      A and S100 were coexpressed by all of the chromatophoromas.

PMID- 21864847
TI  - A double dissociation of memory impairments in major depression.
AB  - Sleep benefits the consolidation of both declarative and nondeclarative memories,
      however the question if these two memory systems profit from sleep in more or
      less similar ways is still under debate. Studying the on-line and off-line
      consolidation of declarative and nondeclarative memory tasks in depressed
      patients and healthy controls, we here present a clear double dissociation
      between memory systems and consolidation phases, suggesting radically different
      ways how sleep benefits memory consolidation. 37 medicated inpatients with an
      acute episode of major depression and 31 healthy controls were assessed using a
      nondeclarative (sequential finger tapping) memory task before and after a night
      with polysomnography, 27 of the depressed and 22 of the control subjects
      additionally performed a declarative (paired associates) task. Although depressed
      patients and control subjects did not differ in practice-dependent learning of
      the nondeclarative motor task in the wake state, healthy subjects showed
      overnight improvements in tapping performance of 11.4%, while the patients'
      performance decreased overnight by 11.5%. This pattern was reversed for the
      declarative task: While patients learned 33.5% less word pairs than controls in
      the wake state, overnight changes did not differ between the two groups. These
      results suggest a double dissociation of memory consolidation processes in major
      depression: Off-line memory consolidation in major depression is impaired for
      nondeclarative, but not declarative tasks. The same tasks in the wake state show
      a reversed pattern, with performance in declarative but not nondeclarative tasks
      being impaired in major depression.

PMID- 21864846
TI  - Mortality reduction by heart rate characteristic monitoring in very low birth
      weight neonates: a randomized trial.
AB  - OBJECTIVE: To test the hypothesis that heart rate characteristics (HRC)
      monitoring improves neonatal outcomes. STUDY DESIGN: We conducted a two-group,
      parallel, individually randomized controlled clinical trial of 3003 very low
      birth weight infants in 9 neonatal intensive care units. In one group, HRC
      monitoring was displayed; in the other, it was masked. The primary outcome was
      number of days alive and ventilator-free in the 120 days after randomization.
      Secondary outcomes were mortality, number of ventilator days, neonatal intensive
      care unit stay, and antibiotic use. RESULTS: The mortality rate was reduced in
      infants whose HRC monitoring was displayed, from 10.2% to 8.1% (hazard ratio,
      0.78; 95% CI, 0.61-0.99; P = .04; number needed to monitor = 48), and there was a
      trend toward increased days alive and ventilator-free (95.9 of 120 days compared
      with 93.6 in control subjects, P = .08). The mortality benefit was concentrated
      in infants with a birth weight <1000 g (hazard ratio, 0.74; 95% CI, 0.57-0.95; P
      = .02; number needed to monitor = 23). There were no significant differences in
      the other outcomes. CONCLUSION: HRC monitoring can reduce the mortality rate in
      very low birth weight infants.

PMID- 21864848
TI  - The handling of absolute values of activity counts by actigraphy.

PMID- 21864849
TI  - Brain structural MRI correlates of cognitive dysfunctions in Parkinson's disease.
AB  - Cognitive dysfunction occurs at early stages of Parkinson's disease (PD). Initial
      studies reported that cognitive dysfunction in early PD only affected fronto
      striatal circuits, provoking a marked executive dysfunction. Memory impairment in
      PD was thought to depend on a problem in retrieving stored information, therefore
      also reflecting a fronto-striatal dysfunction. However, there is increasing
      structural MRI evidence of medial temporal lobe atrophy in PD, which may be
      responsible for memory dysfunction. Other neuropsychological functions usually
      impaired in PD are semantic fluency, visuoperceptual and visuospatial functions,
      decision-making and recognition of facial emotions; and impairments in these
      functions are associated with cortical structural changes assessed by MRI.
      Overall, although the literature on the topic is scarce, there is increasing
      evidence of brain structural changes, detectable by MRI, which can explain the
      neuropsychological deficits early in the clinical disease course before dementia
      develops. In this review, we summarize the papers that have used structural MRI
      to study the neuroanatomical correlates of cognitive dysfunctions in PD.

PMID- 21864850
TI  - From research to clinical practice: implementation of functional magnetic imaging
      and white matter tractography in the clinical environment.
AB  - In the last two decades functional magnetic resonance imaging (fMRI) has
      dominated research in neuroscience. However, only recently has it taken the first
      steps in translation to the clinical field. In this paper we describe the
      advantages of fMRI and DTI and the possible benefits of implementing these
      methods in clinical practice. We review the current clinical usages of fMRI and
      DTI and discuss the challenges and difficulties of translating these methods to
      clinical use. The most common application today is in neurosurgery. fMRI and DTI
      are done preoperatively for brain tumor patients who are having tumors removed
      and for epilepsy patients who are candidates for temporal resection. Imaging
      results supply the neurosurgeon with essential information regarding possible
      functional damage and thereby aid both in planning and performing surgery.
      Scientific research suggests more promising potential implementations of fMRI and
      DTI in improving diagnosis and rehabilitation. These advanced imaging methods can
      be used for pre-symptomatic diagnosis, as a differentiating biomarker in the
      absence of anatomical measurements, and for identification of mental response in
      the absence of motor-sensory abilities. These methods can aid and direct
      rehabilitation by predicting the success of possible interventions and
      rehabilitation options and by supplying a measure for biofeedback. This review
      opens a window to the state of the art neuroimaging methods being implemented
      these days into the clinical practice and provides a glance to the future
      clinical possibilities of fMRI and DTI.

PMID- 21864851
TI  - Evaluation of apoptosis-related genes: Fas (CD94), FasL (CD178) and TRAIL
      polymorphisms in Iranian multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating disease
      characterized by a relapsing-remitting course leading to progressive disability.
      Given the critical role of apoptosis-related genes in the maintenance of
      homeostasis in the immune privilege sites, mutations in these genes have a
      profound effect on occurring autoimmune diseases such as multiple sclerosis. In
      the current study, polymorphisms in the apoptosis-related genes: Fas _-670 A>G,
      FasL _-844C>T, FasLIVS2nt _124 A>G and TRAIL_1595C>T were analyzed in 107 Iranian
      patients suffering from MS and 112 unrelated healthy controls using PCR-RFLP
      method. Our results demonstrated that among Iranian patients with MS and controls
      being homozygous in Fas_670A/A, G/G and FasL_-844C/C, TT in the promoter region
      and homozygocity in the minor allele for FasLIVS2nt_124G/G and TRAIL_1595C/C,
      polymorphisms were not associated with the MS risk in Iranian patients when
      compared with normal controls. However, the Fas _-670G/G genotype had a
      borderline significantly increased frequency with secondary progressive MS type
      (X(2)=5.8, P=0.05). In conclusion, no statistical association was found between
      the Fas, FasL and TRAIL polymorphisms and the risk of MS in Iranian patients.

PMID- 21864852
TI  - Ascending-descending aortic bypass with valve-sparing root replacement for
      coarctation with aortic root aneurysm.

PMID- 21864853
TI  - Historical perspectives of The American Association for Thoracic Surgery: John
      Gordon Scannell (1914-2002).

PMID- 21864854
TI  - Long-term survival after lung resection for non-small cell lung cancer with
      circulatory bypass: a systematic review.
AB  - OBJECTIVE: Resection of locally advanced non-small cell lung cancer using
      circulatory bypass is not frequently performed. The objective of this study was
      to systematically review the long-term survival associated with the published
      studies dealing with the performance of lung resections for non-small cell lung
      cancer using circulatory bypass. METHODS: A systematic review of publications
      dealing with lung resections for non-small cell lung cancer under circulatory
      bypass spanning from January 1, 1990, to December, 31 2010, was performed using a
      PubMed search with specific inclusion and exclusion criteria. The primary end
      point collected was survival. Several other clinical variables were also
      collected and analyzed. Survival curves were calculated using the Kaplan-Meier
      method. Univariate comparisons of survival were performed using a Cox
      proportional hazard model. Multivariate analysis was carried out using a Cox
      regression model. RESULTS: The search algorithm yielded 20 articles for the
      analysis. The overall 5-year survival was 37% (median, 36 +/- 6 months). Survival
      was significantly higher when placement on bypass was planned (54%; median, 67 +/
      19 months) as opposed to unplanned or emergency placement (11%; median, 19 +/- 6
      months; P = .006). Multivariate analysis demonstrated that the use of unplanned
      bypass was prognostic for a worse long-term survival (hazard ratio = 0.28; 95%
      confidence interval, 0.09-0.90; P = .033). The 30-day and 90-day perioperative
      mortalities were 0% and 1%, respectively. CONCLUSIONS: The literature over the
      past 2 decades demonstrates that favorable long-term survival for extended
      resections of locally advanced non-small cell lung cancer using circulatory
      bypass can be achieved. The use of unplanned cardiopulmonary bypass, though,
      seems to be prognostic of unfavorable long-term survival.

PMID- 21864855
TI  - Risk of recurrent gastrointestinal bleeding after aortic valve replacement in
      patients with Heyde syndrome.
AB  - OBJECTIVE: We sought to evaluate the effectiveness of aortic valve replacement
      for reducing gastrointestinal bleeding in patients with Heyde syndrome, in whom
      gastrointestinal bleeding is associated with intestinal angiodysplasia and aortic
      valve stenosis. METHODS: We conducted a retrospective review of patients treated
      at the Mayo Clinic between 1971 and 2007 for gastrointestinal bleeding and
      intestinal angiodysplasia who later underwent aortic valve replacement for severe
      aortic valve stenosis. We analyzed early and late outcomes, including recurrent
      gastrointestinal hemorrhage. RESULTS: Fifty-seven patients (39 men and 18 women)
      were identified. At operation, the median age of patients was 75 years.
      Intestinal angiodysplasia occurred most commonly in the duodenum and right side
      of the colon. Before aortic valve replacement, the mean number of bleeding
      episodes was 12 per patient-year; 48 patients (84%) required blood transfusions.
      Bioprosthetic valves were used in 47 patients. During follow-up extending to 15
      years, 45 patients (79%) had no recurrence of bleeding. In patients who
      experienced recurrent bleeding, the episodes were reduced from a mean +/-
      standard deviation of 4.7 +/- 7 episodes per patient-year to 1.9 +/- 2 per
      patient-year. Recurrent bleeding occurred only in patients with lesions of the
      duodenum or right colon. Among patients who received bioprostheses, the overall
      risk of recurrent bleeding was 15%, lower than the 50% risk of subsequent
      gastrointestinal bleeding with mechanical prostheses. CONCLUSIONS: Aortic valve
      replacement seems to decrease the risk of gastrointestinal bleeding in patients
      with Heyde syndrome and is curative in approximately 80%. Although rates of
      recurrent bleeding were not significantly different between the 2 prosthetic
      valve types, the higher risk of bleeding in patients receiving warfarin makes
      bioprosthetic valves the valve of choice for most patients.

PMID- 21864856
TI  - Continuous biatrial pacing to prevent early recurrence of atrial fibrillation
      after the Maze procedure.
AB  - OBJECTIVE: It has been suggested that overdrive biatrial pacing may prevent the
      recurrence of atrial fibrillation after the Maze procedure. To further evaluate
      this hypothesis, we performed a randomized prospective study in 100 patients
      undergoing valve surgery concomitant with a full Maze procedure to determine the
      effectiveness of biatrial pacing in the postoperative period to reduce early
      recurrence of atrial fibrillation. METHOD: Between January 2002 and December
      2008, 100 patients undergoing mitral valve +/- tricuspid valve surgery
      concomitant with the Maze procedure were randomized into 2 equal groups: the
      study group using overdrive biatrial pacing and a control group without pacing.
      One pacing wire was attached to the crista terminalis area of the right atrium,
      and the other pacing wire was attached to the Bachmann's bundle area located in
      the roof of the left atrium. The atria were paced continuously in AAI mode at a
      rate of 80 pulses per minute or 10 pulses above the underlying rate for 5 days.
      The end points were the onset of recurrent atrial fibrillation or discharge.
      RESULTS: The incidence of recurrent postoperative atrial fibrillation was
      significantly less in the study group, with 6 of 50 patients (12%) incurring
      atrial fibrillation compared with 18 of 50 patients (36%) in the control group (P
      < .01). The length of hospital stay was significantly reduced in the study group
      (P < .01), and the mean costs of hospital stay were significantly lower in the
      control group (P < .05). CONCLUSIONS: Biatrial overdrive pacing is well tolerated
      and more effective in preventing the early recurrence of atrial fibrillation
      after the Maze procedure. This therapy also results in shortened hospital stays
      and decreased hospital costs. However, the impacts of the long-term results in
      the Maze procedure require further study.

PMID- 21864857
TI  - Early thrombosis risk in patients with biologic valves in the aortic position.
AB  - OBJECTIVE: Patients who require aortic valve replacement are increasingly
      receiving biologic valves to avoid long-term anticoagulation. The thromboembolic
      risk of bioprosthetic valves is reportedly low. The study objective was to review
      the incidence of early valve thrombosis requiring reoperation in patients who
      received a bioprosthetic valve in the aortic position. METHODS: We reviewed all
      adult patients who had a biologic valve implanted in the aortic position at Mayo
      Clinic between January 1993 and July 2009. Records were reviewed for all cases of
      reoperation that occurred less than 2 years postoperatively. Incidences of valve
      thrombosis were calculated including 95% Poisson confidence intervals. RESULTS:
      During the study interval, 4568 patients received biologic valves for aortic
      valve replacement. We identified 8 patients who underwent reoperation to replace
      the aortic prosthesis because of thrombus that resulted in functional aortic
      stenosis. The median age of patients at the time of reoperation was 77 years
      (range, 52-86), and the median time to reoperation was 398 days (range, 106-626).
      All patients with valve thrombosis received a stented porcine valve: St Jude
      Biocor (St Jude Medical, Inc, St Paul, Minn) in 4 patients, Medtronic Mosaic
      (Medtronic Inc, Minneapolis, Minn) in 2 patients, and Medtronic Hancock
      (Medtronic Inc) in 2 patients. The calculated incidence of valve thrombosis was
      1.26% (confidence interval, 0.56-1.96) for the Biocor valve, 0.37% (confidence
      interval, 0.19-0.56) for the Mosaic valve, and 0.84% (confidence interval, 0.42
      1.25) for the Hancock valve (P = .34). There were no cases of valve thrombosis in
      patients who received a pericardial valve (5923 patient-years) or stentless valve
      (172 patient-years). CONCLUSIONS: The incidence of early thrombosis of porcine
      aortic bioprostheses requiring reoperation was not insignificant. Potential
      causes and mechanisms for such thrombosis are unknown. Recognition of this
      unanticipated problem and reoperation resulted in a satisfactory outcome for
      patients.

PMID- 21864859
TI  - Analysis of bacterial diversity and metals in produced water, seawater and
      sediments from an offshore oil and gas production platform.
AB  - Produced water is one of the largest waste products routinely discharged into the
      ocean from offshore oil and gas platforms. This study analyzed bacterial
      communities and metals in the produced water, surrounding seawater, and sediment
      around the Thebaud platform. The bacterial community within the produced water
      was different from the seawater (SAB=13.3), but the discharge had no detectable
      effect on the bacterial communities in the seawater (SAB>97). In contrast,
      genomic analysis of sediments revealed that the bacterial community from 250 m
      was different (SAB=70) from other locations further from the discharge,
      suggesting that the produced water had a detectable effect on the bacterial
      community in the sediment closest to the discharge. These near-field sediments
      contained elevated concentrations of manganese and iron that are associated with
      the produced water effluent. The results suggested that the discharge of produced
      water has influenced the bacterial community structure of sediments adjacent to
      the platform.

PMID- 21864860
TI  - Storm petrel's breeding skipping in response to oil-spill pollution: raising
      concerns over Zabala et al. (2011) methodological approach.

PMID- 21864861
TI  - Marine debris ingestion by Magellanic penguins, Spheniscus magellanicus (Aves:
      Sphenisciformes), from the Brazilian coastal zone.
AB  - Magellanic penguins (Spheniscus magellanicus) are non-breeding winter visitors to
      the Brazilian coast. In 2008 and 2010, plastic items and other marine debris were
      found in the stomachs and intestines of 15% of 175 dead penguins collected in the
      Lagos Region of the state of Rio de Janeiro. One bird had its stomach perforated
      by a plastic straw, which may have caused its death. There are few records of
      penguins ingesting plastic litter, but previous studies have found similar levels
      of debris ingestion among Magellanic penguins stranded on the Brazilian coast
      (35.8% of 397 birds). The high incidence of marine debris in this species in
      Brazil may result at least in part from the predominance of juveniles reaching
      these waters, as juvenile penguins may have a broader diet than adults. It is
      unclear to what extent plastic ingestion affects the mortality rate in this
      species and whether the incidence in stranded birds reflects that in the entire
      population. The present study addresses the increasing impact of plastic debris
      on marine life.

PMID- 21864862
TI  - Rapid macrofaunal colonization of water-based drill cuttings on different
      sediments.
AB  - A field experiment was conducted to investigate how water-based drill cuttings
      and sediment type influence colonization of soft bottom communities. Bottom
      frames with trays containing defaunated sediments were placed at the seabed for 6
      months to study colonization of macrofauna. Two different sediments (coarse and
      fine) were used, and 6 or 24 mm layer of water-based drill cuttings were added on
      top of these sediments. Some of the sediments were controls with no additions. In
      the end of the experiment, the oxygen availability in sediment porewater and
      macrofaunal abundance were reduced in treatments with 24 mm drill cuttings
      compared to controls. Tube-building annelids were particularly sensitive to drill
      cuttings. However, these responses were only minor, and notably, the drill
      cuttings initiated a weaker faunal response than sediment type and site of the
      bottom frame. Sediments capped with water-based drill cuttings thus showed a
      rapid colonization of macrofaunal communities.

PMID- 21864863
TI  - Study of the spatial and historical distribution of sediment inorganic
      contamination in the Toulon bay (France).
AB  - This study presents trace elements levels in surface and deep sediments of the
      Toulon bay (SE France) subjected to anthropogenic inputs (navy base, harbors,
      etc.). The studied elements (As, Cd, Cr, Cu, Hg, Ni, Pb, Zn) are defined as
      priority contaminants in aquatic systems. Fifty-five points scattered on the
      entire bay were sampled, allowing the determination of contaminants distribution
      with a high resolution. Several approaches were used to assess the degree of
      contamination and the potential toxicity of the Toulon bay sediments: comparison
      to the French legislation, surface-weighted average metal concentrations,
      enrichment factors (EF), geoaccumulation indices (Igeo), trace element stock
      calculation and comparison to sediment quality guidelines. A principal component
      analysis was performed to reveal common behavior of the studied contaminants.
      Results demonstrated the very high contamination of the small bay, especially in
      Hg (EF up to 1500), Cu, Pb and Zn, with export to the large bay further governed
      by hydrodynamics.

PMID- 21864864
TI  - High serum uric acid level and low urine pH as predictors of metabolic syndrome:
      a retrospective cohort study in a Japanese urban population.
AB  - The objective of this study was to evaluate whether hyperuricemia, acidic urine,
      or their combination predicts metabolic syndrome (MetS). In study 1, 69,094
      subjects who received a general health checkup between 1985 and 2005 were
      included in a cross-sectional study of serum uric acid (SUA) and urine pH in
      relation to MetS. In study 2, the association of SUA and urine pH with MetS
      development over a 5-year period was evaluated in 5617 subjects with body mass
      index less than 25 kg/m(2) at the first examination. In study 1, higher SUA and
      lower urine pH were both positively correlated to MetS status (P < .001). The
      combination of high SUA and low urine pH was significantly associated with higher
      MetS prevalence compared with the combination of low SUA and high urine pH (odds
      ratio, 3.383; 95% confidence interval [CI], 3.034-3.784 in men; odds ratio,
      4.000; 95% CI, 2.992-5.452 in women). In study 2, the top quartile of SUA levels
      was associated with higher MetS development compared with the bottom quartile
      during the 5-year period in men (hazard ratio [HR], 1.793; 95% CI, 1.084-2.966; P
      = .023). In women, the HR was 3.732 (95% CI, 0.391-35.62; P = .252) for the upper
      vs the lower half of SUA levels. For urine pH, the HR was 1.955 (95% CI, 1.089
      3.509; P = .025) for the bottom vs the top quartile in men. A likelihood ratio
      test confirmed that high SUA and low urine pH act synergistically in the
      development of MetS. High SUA, low urine pH, and their combination are predictive
      risk factors for MetS development.

PMID- 21864865
TI  - Effect of exercise training combined with phytoestrogens on adipokines and C
      reactive protein in postmenopausal women: a randomized trial.
AB  - Phytoestrogens and training could be effective to reduce cardiovascular and type
      2 diabetes mellitus risk factors in postmenopausal women. Nevertheless, the
      impact of their combination on adipokines and systemic inflammation was never
      investigated. The objective was to verify if 6 months of mixed training combined
      with phytoestrogens could have an additional effect on adipokine levels and
      systemic inflammation in obese postmenopausal women. Fifty-two obese women aged
      between 50 and 70 years were randomly assigned to (1) exercise with placebo (EX +
      PL; n = 25) or (2) exercise with phytoestrogens (EX + PHY; n = 27). Body weight,
      waist circumference, fat mass, and lean body mass (dual-energy x-ray
      absorptiometry) were assessed. Fasting plasma glucose and insulin, adiponectin,
      leptin, and C-reactive protein (CRP) levels were obtained after a 12-hour
      overnight fast. Total energy intake was measured with a 3-day dietary record. All
      measurements were performed before and after the 6-month intervention. Although
      energy intake remained unchanged, body composition was improved in all women (all
      Ps < .02). Plasma CRP and leptin levels decreased in both groups similarly (all
      Ps < .03), whereas plasma adiponectin and insulin did not change with exercise
      combined with placebo or phytoestrogens. Correlation analyses showed that
      homeostasis model assessment of insulin resistance (r = -0.58, P = .02) and
      fasting insulin levels (r = -0.42, P = .02) at baseline were both correlated with
      changes in leptin levels. Baseline fasting glucose (r = -0.36, P = .03) and
      adiponectin (r = 0.45, P = .005) levels were associated with changes in CRP
      concentrations. Although mixed exercise program combined with phytoestrogens does
      not seem to provide any additional effect, mixed training improves systemic
      inflammation and leptin concentrations in obese postmenopausal women.

PMID- 21864866
TI  - Combined hypertriglyceridemic and insulin-glucose clamps for the characterization
      of substrate oxidation and plasma elimination of a long-chain triglyceride
      emulsion in healthy men.
AB  - This study examines the effect of glucose and insulin on the plasma elimination
      rate and oxidation of a fat emulsion by using indirect calorimetry in conjunction
      with lipid and insulin-glucose clamp techniques. Ten healthy subjects were
      studied on 2 occasions in a randomized, open, crossover study. On one occasion, a
      hypertriglyceridemic (HTG) clamp was administrated alone; and, on the other, HTG
      and insulin-glucose (IG) clamps were administrated simultaneously. During HTG
      clamps, serum triglyceride (TG) concentration was maintained at 4 mmol * L(-1).
      During the IG clamp, insulin was administered at a rate of 20 mU * m(-2) * min(
      1); and the glucose level was maintained at 7 mmol * L(-1). Continuous indirect
      calorimetry was carried out throughout the study period. The infusion rate
      required to maintain stable serum TG concentrations did not differ between the 2
      clamps. Mean free fatty acid concentration was lower during the HTG/IG than
      during the HTG clamp (0.40 +/- 0.04 vs 0.82 +/- 0.07 mmol * L(-1); P < .001).
      However, the increases in beta-OH-butyrate levels were significantly lower in the
      HTG/IG compared with the HTG clamp (0.09 +/- 0.04 vs 0.55 +/- 0.09 mmol * L(-1);
      P < .001). Energy expenditure and the respiratory quotient were significantly
      higher at steady state in the HTG/IG than in the HTG clamp: 1.47 +/- 0.06 vs 1.34
      +/- 0.04 kcal * min(-1) (P < .01) and 0.85 +/- 0.01 vs 0.79 +/- 0.01 (P < .01),
      respectively. Insulin and glucose did not significantly change plasma TG disposal
      rate (P = .0987) or total lipid oxidation (P = .3204) in this metabolic situation
      with an abundant supply of both carbohydrates and lipids. beta-OH-butyrate
      increased during both clamps, indicating an ongoing hepatic fatty oxidation
      despite the administration of glucose/insulin.

PMID- 21864867
TI  - The effects of glucocorticoids on adipose tissue lipid metabolism.
AB  - Glucocorticoids (GCs) have long been accepted as being catabolic in nature,
      liberating energy substrates during times of stress to supply the increased
      metabolic demand of the body. The effects of GCs on adipose tissue metabolism are
      conflicting, however, because patients with elevated GCs present with central
      adiposity. We performed an extensive literature review of the effects of GCs on
      adipose tissue metabolism. The contradictory effects of GCs on lipid metabolism
      occur through a number of different mechanisms, some of which are well defined
      and others remain to be elucidated. Firstly, through increases in caloric and
      dietary fat intake, along with increased hydrolysis of circulating triglycerides
      (chylomicrons, very low-density lipoproteins) by lipoprotein lipase activity, GCs
      increase the amount of fatty acids in circulation, which are then available for
      ectopic fat distribution (liver, muscle, and central adipocytes). Glucocorticoids
      also increase de novo lipid production in hepatocytes through increased
      expression of fatty acid synthase. There is some controversy as to whether these
      same mechanisms occur in adipocytes, thereby contributing to adipose hypertrophy.
      Glucocorticoids promote preadipocyte conversion to mature adipocytes, causing
      hyperplasia of the adipose tissue. Glucocorticoids also have acute antilipolytic
      effect on adipocytes, whereas their genomic actions facilitate increased
      lipolysis after about 48 hours of exposure. The acute and long-term effects of
      GCs on adipose tissue lipolysis remain unclear. Although considerable evidence
      supports the notion that GCs increase lipolysis through glucocorticoid-induced
      increases of lipase expression, they clearly have antilipolytic effects within
      these same tissues and cell line models.

PMID- 21864868
TI  - Improvement in insulin sensitivity following a 1-year lifestyle intervention
      program in viscerally obese men: contribution of abdominal adiposity.
AB  - The objectives of the study were to quantify the effect of a 1-year healthy
      eating-physical activity/exercise lifestyle modification program on insulin
      sensitivity in viscerally obese men classified according to their glucose
      tolerance status and to evaluate the respective contributions of changes in body
      fat distribution vs changes in cardiorespiratory fitness (CRF) to the
      improvements in indices of plasma glucose/insulin homeostasis. Abdominally obese,
      dyslipidemic men (waist circumference >=90 cm, triglycerides >=1.69 mmol/L,
      and/or high-density lipoprotein cholesterol <1.03 mmol/L) were recruited. The 1
      year intervention/evaluation was completed by 104 men. Body weight, composition,
      and fat distribution were assessed by dual-energy x-ray absorptiometry/computed
      tomography. Cardiorespiratory fitness and cardiometabolic risk profile were
      measured. After 1 year, insulin sensitivity improved in association with
      decreases in both visceral (VAT) and subcutaneous adiposity (SAT) as well as with
      the improvement in CRF, regardless of baseline glucose tolerance. Further
      analyses were performed according to changes in glucose tolerance status:
      improvement (group I, n = 39), no change (group N, n = 50), or worsening (group
      W, n = 15) after 1 year. Groups I and N improved their insulin sensitivity and
      their CRF, whereas group W did not, while losing less VAT than groups I and N.
      Multiple regressions showed that reduction in VAT was associated with an
      improvement in homeostasis model assessment of insulin resistance, whereas
      reduction in SAT was rather associated with improvement of the insulin
      sensitivity index of Matsuda. Changes in CRF were not independently associated
      with changes in indices of plasma glucose/insulin homeostasis. A 1-year lifestyle
      intervention improved plasma glucose/insulin homeostasis in viscerally obese men,
      including those with normal glucose tolerance status at baseline. Changes in SAT
      and VAT but not in CRF appeared to mediate these improvements.

PMID- 21864869
TI  - Acute resistance exercise augments integrative myofibrillar protein synthesis.
AB  - The purpose of this study was to determine whether an acute bout of high
      intensity resistance exercise (RE) would augment integrative mixed muscle and
      myofibrillar protein fractional synthesis rates (FSRs) when total energy and
      macronutrient intake was controlled. Twelve healthy young men were studied over
      24 hours and performed an acute bout of exhaustive (5 sets until volitional
      failure of their 85% 1-repetition maximum) unilateral leg press and knee
      extension exercise, such that one leg was exercised (EX) and the other served as
      a control (CON). (2)H(2)O (70%) was provided to measure mixed muscle and
      myofibrillar FSR, and muscle biopsies (vastus lateralis) were collected from the
      EX and CON legs 16 hours following the RE session. (2)H-labeling of body water
      over the course of the experiment was 0.32 +/- 0.01 mole percent excess.
      Interestingly, integrative mixed muscle FSR (percent per hour) was similar
      between the CON (0.76% +/- 0.08%) and EX (0.69% +/- 0.06%) legs. In contrast,
      upon determination of myofibrillar FSR, there was an RE effect (EX, 0.94% +/-
      0.16% vs CON, 0.75% +/- 0.08%; P < .05). High-intensity RE without prior training
      impacts integrative myofibrillar 24-hour FSR, perhaps without altering total
      responses.

PMID- 21864870
TI  - Structure elucidation and hepatotoxicity evaluation against HepG2 human cells of
      neo-clerodane diterpenes from Teucrium polium L.
AB  - Seven neo-clerodanes (teupolins VI-XII) and eleven known compounds were isolated
      and characterized from leaf extracts of Teucrium polium L., a medicinal plant
      used in traditional and herbal medicine for its hypolipidemic, hypoglycemic,
      antioxidant and antiproliferative properties. The structures of these compounds
      were elucidated by 1D (1H, 13C and DEPT) and 2D (COSY, TOCSY, HSQC, HMBC) NMR
      experiments and by mass spectrometry analysis. The complete stereostructure of
      each compound was defined with a NOESY experiment. Because the overexploitation
      of herbal remedies containing T. polium extracts has resulted in several cases of
      hepatitis, the hepatotoxic activity of pure metabolites against the human
      hepatoblastoma cancer cell line HepG2 was assessed by the MTT (3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) test. All of the compounds showed
      low toxicity values at the highest concentration tested (200 MUM).

PMID- 21864871
TI  - Development of an online tool for public health: the European Public Health Law
      Network.
AB  - BACKGROUND: The European Public Health Law Network was established in 2007 as
      part of the European Union (EU) co-funded Public Health Law Flu project. The aims
      of the website consisted of designing an interactive network of specialist
      information and encouraging an exchange of expertise amongst members. The website
      sought to appeal to academics, public health professionals and lawyers. METHODS:
      The Public Health Law Flu project team designed and managed the website.
      Registered network members were recruited through publicity, advertising and word
      of mouth. Details of the network were sent to health organizations and
      universities throughout Europe. Corresponding website links attracted many new
      visitors. Publications, news, events and a pandemic glossary became popular
      features on the site. Although the website initially focused only on pandemic
      diseases it has grown into a multidisciplinary website covering a range of public
      health law topics. RESULTS: The network contains over 700 publications divided
      into 28 public health law categories. News, events, front page content,
      legislation and the francophone section are updated on a regular basis. Since
      2007 the website has received over 15,000 views from 156 countries. Newsletter
      subscribers have risen to 304. There are now 723 followers on the associated
      Twitter site. CONCLUSION: The European Public Health Law Network has been a
      successful and innovative site in the area of public health law. Interest in the
      site continues to grow. Future funding can contribute to a bigger site with
      interactive features and pages in a wider variety of languages to attract a wider
      global audience.

PMID- 21864872
TI  - Evaluation of the knowledge of primary healthcare patients in Poland on the
      prevention of hypertension: a community study.
AB  - OBJECTIVES: To investigate the knowledge of Poles on the prevention of arterial
      hypertension (HT) and identify the main souces of knowledge in order to make
      health promotion activities more effective, and thus increase the efficiency and
      efficacy of the Polish healthcare system. STUDY DESIGN: Community study. METHODS:
      This questionnaire study included 180 subjects (120 primary healthcare patients
      without a history of diagnosed HT and 60 primary care physicians). RESULTS: The
      knowledge of most surveyed patients was insufficient (43%, n = 52) or sufficient
      (40%, n = 48) for the effective prevention of HT; 17% (n = 20) of the respondents
      had knowledge that was definitely sufficient, and none of the respondents had
      knowledge that was definitely insufficient. The patients reported that primary
      care physicians were the most common source of health information (67%, n = 80).
      Primary care physicians were also the most trusted source of information.
      CONCLUSIONS: Patients' knowledge on smoking, diet and exercise is sufficient for
      the effective prevention of HT. The areas of insufficient knowledge for the
      development of HT and possible organ complications are drinking alcohol, stress,
      genetic factors and diabetes.

PMID- 21864873
TI  - Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T.
AB  - The purpose of this study was to evaluate the feasibility of proton magnetic
      resonance spectroscopy (1H MRS) to study the concentration of metabolites in the
      brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0
      T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained
      showed that all dogs had excellent quality spectra for a small (1 cm3) and large
      (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due
      to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable
      method to study metabolite concentrations in the canine brain. The development of
      more advanced water suppression techniques is necessary to improve the results at
      7.0 T.

PMID- 21864874
TI  - The effect of supplementation of flax-seed oil on interaction of Lactobacillus
      plantarum--BiocenolTM LP96 and Escherichia coli O8:K88ab:H9 in the gut of germ
      free piglets.
AB  - We investigated the influence of administration of flax-seed oil on interaction
      of Lactobacillus plantarum - BiocenolTM LP96 and Escherichia coli O8:K88ab:H9 in
      the gut of germ-free piglets. When compared to animals supplemented with L.
      plantarum, the counts of lactobacilli in the jejunal and ileal mucosa and in the
      intestinal content were significantly higher in LMK group (p<0.0001). Inter
      groups comparison of the counts of E. coli K88 adhering to the jejunal and ileal
      mucosa revealed a significantly decrease in LMK animals (p<0.001; p<0.05).

PMID- 21864875
TI  - Evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal
      reflux episodes in anesthetized dogs.
AB  - This research aimed to evaluate the effect of metoclopramide and ranitidine in
      the prevention of gastroesophageal reflux episodes during anesthetic procedures.
      Ninety healthy female dogs were submitted to elective ovariosalpingohisterectomy,
      randomly divided into three groups of 30 animals. The control group received only
      the anesthetic protocol. The metoclopramide group received an intravenous bolus
      of 1mg/kg, and continuous infusion (1 mg/kg/h intravenously) immediately after
      anesthetic induction. The ranitidine group received an intravenous bolus of 2
      mg/kg, 6 h before anesthesia. Anesthesia (acepromazine, propofol and isofluorane)
      was standardized and the esophageal pH variations were recorded. Esophagoscopy
      was carried out after surgery. No difference (p<0.05) was verified in the reflux
      episodes between the groups. Seven animals presented reflux. Metoclopramide in
      bolus and continuous infusion, as well as ranitidine, 6 h before anesthesia, did
      not influence the reduction of the incidence of gastroesophageal reflux.

PMID- 21864876
TI  - Packaging and structural phenotype of brome mosaic virus capsid protein with
      altered N-terminal beta-hexamer structure.
AB  - The first 45 amino acid region of brome mosaic virus (BMV) capsid protein (CP)
      contains RNA binding and structural domains that are implicated in the assembly
      of infectious virions. One such important structural domain encompassing amino
      acids 28QPVIV32, highly conserved between BMV and cowpea chlorotic mottle virus
      (CCMV), exhibits a beta-hexamer structure. In this study we report that
      alteration of the beta-hexamer structure by mutating 28QPVIV32 to 28AAAAA32 had
      no effect either on symptom phenotype, local and systemic movement in Chenopodium
      quinoa and RNA profile of in vivo assembled virions. However, sensitivity to
      RNase and assembly phenotypes distinguished virions assembled with CP subunits
      having beta-hexamer from those of wild type. A comparison of 3-D models obtained
      by cryo electron microscopy revealed overall similar structural features for wild
      type and mutant virions, with small but significant differences near the 3-fold
      axes of symmetry.

PMID- 21864877
TI  - Fenton-like initiation of a toluene transformation mechanism.
AB  - In Fenton-driven oxidation treatment systems, reaction intermediates derived from
      parent compounds can play a significant role in the overall treatment process.
      Fenton-like reactions in the presence of toluene or benzene, involved a
      transformation mechanism that was highly efficient relative to the conventional
      Fenton-driven mechanism. A delay in hydrogen peroxide (H2O2) reaction occurred
      until the complete or near-complete transformation of toluene or benzene and
      involved the simultaneous reaction of dissolved oxygen. This highly efficient
      transformation mechanism is initiated by Fenton-like reactions, and therefore
      dependent on conventional Fenton-like parameters. Results indicated that several
      potential parameters and mechanisms did not play a significant role in the
      transformation mechanism including electron shuttles, Fe chelates, high valent
      oxo-iron complexes, anionic interferences in H2O2 reaction, and H2O2 formation.
      The Fenton-like initiation, formation, and propagation of a reaction intermediate
      species capable of transforming toluene, while simultaneously inhibiting H2O2
      reaction is the most viable mechanism.

PMID- 21864878
TI  - Removal of persistent pharmaceutical micropollutants from sewage by addition of
      PAC in a sequential membrane bioreactor.
AB  - The performance of a membrane bioreactor operating in a sequential mode (SMBR)
      using an external flat-plate membrane was investigated. After 200 days of
      operation, a single addition of 1 g L(-1) Powdered Activated Carbon (PAC) was
      added directly into the mixed liquor in order to enhance the simultaneous removal
      of nutrients and pharmaceutical micropollutants from synthetic urban wastewater.
      Throughout the entire operation (288 days), Chemical Oxygen Demand (COD) removal
      efficiencies were up to 95%, ammonium nitrogen removal was maintained over 70
      80%, whereas phosphorus removal achieved only high values (around 80%) after PAC
      addition. During the operation of the SMBR without PAC addition, micropollutants
      which exerted a more recalcitrant behaviour were carbamazepine, diazepam,
      diclofenac and trimethoprim, with no significant removal. On the other hand,
      moderate removals (42-64%) were observed for naproxen and erythromycin, whereas
      ibuprofen, roxithromycin and fluoxetine were removed in the range of 71-97%. The
      addition of PAC into the aeration tank was a successful tool to improve the
      removal of the more recalcitrant compounds up to 85%. The highest removal with
      PAC was observed for carbamazepine, trimethoprim as well as for roxithromycin,
      erythromycin and fluoxetine. The latter four compounds have amine groups and pKa
      in the range 6.7-10.1, thus the interaction between PAC and the positively
      charged amino groups might be the cause of their comparatively better results.
      Microbial ecology present in the biomass showed a higher abundance of
      Accumulibacter phosphatis as well as the ammonium oxidizing bacteria belonging to
      the genus Nitrosomonas after PAC addition.

PMID- 21864879
TI  - Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in
      an advanced wastewater reclamation plant.
AB  - The occurrence of nineteen pharmaceutically active compounds and personal care
      products was followed monthly for 12 months after various stages of treatment in
      an advanced wastewater reclamation plant in Gwinnett County, GA, U.S.A. Twenty
      four hour composite samples were collected after primary clarification, activated
      sludge biological treatment, membrane filtration, granular media filtration,
      granular activated carbon (GAC) adsorption, and ozonation in the wastewater
      reclamation plant. Compounds were identified and quantified using high
      performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) and gas
      chromatography/mass spectrometry (GC-MS) after solid-phase extraction. Standard
      addition methods were employed to compensate for matrix effects. Sixteen of the
      targeted compounds were detected in the primary effluent; sulfadimethoxine,
      doxycycline, and iopromide were not found. Caffeine and acetaminophen were found
      at the highest concentrations (~10(5) ng/L), followed by ibuprofen (~10(4) ng/L),
      sulfamethoxazole and DEET (~10(3) ng/L). Most of the other compounds were found
      at concentrations on the order of hundreds of ng/L. After activated sludge
      treatment and membrane filtration, the concentrations of caffeine, acetaminophen,
      ibuprofen, DEET, tetracycline, and 17alpha-ethynylestradiol (EE2) had decreased
      by more than 90%. Erythromycin and carbamazepine, which were resistant to
      biological treatment, were eliminated by 74 and 88%, on average, by GAC.
      Primidone, DEET, and caffeine were not amenable to adsorption by GAC. Ozonation
      oxidized most of the remaining compounds by >60%, except for primidone and DEET.
      Of the initial 16 compounds identified in the primary effluent, only
      sulfamethoxazole, primidone, caffeine and DEET were frequently detected in the
      final effluent, but at concentrations on the order of 10-100 ng/L. Removal of the
      different agents by the various treatment processes was related to the physical
      chemical properties of the compounds.

PMID- 21864880
TI  - Disinfection by-product dynamics in a chlorinated, indoor swimming pool under
      conditions of heavy use: national swimming competition.
AB  - Anecdotal evidence suggests that water quality in chlorinated, indoor pools
      deteriorates under conditions of heavy use. However, data to define these
      dynamics have not been reported. To address this issue, a study was performed in
      which water chemistry was monitored in a chlorinated, indoor pool before and
      during a national swimming competition, a period of heavy, intense use. NCl3
      concentration was observed to double after the first day, and increased by a
      factor of 3-4 over the 4 days of competition. CNCHCl2 and CH3NCl2 concentrations
      both increased by a factor of 2-3 during the course of the meet, while CHCl3
      concentration showed only a modest increase during this same period. Diurnal
      patterns of NCl3, CH3NCl2 and CHCl3 concentrations were observed, and these
      patterns appeared to depend on the Henry's law constant of the compound. Urea
      concentration showed a diurnal pattern, superimposed on a trend of steady
      increase during each day of the competition; however, the diurnal pattern of urea
      behavior could not be explained by reactions with chlorine, as the urea-free
      chlorine reaction is relatively slow. It is more likely that the overnight
      decrease in urea concentration was attributable to mixing of surface water with
      water in the deeper parts of the pool. The findings of this study provide an
      indication of the changes in pool water chemistry that take place in a
      chlorinated, indoor pool under heavy use conditions.

PMID- 21864881
TI  - Supplementation of inorganic phosphate enhancing the removal efficiency of
      tannery sludge-borne Cr through bioleaching.
AB  - Four inorganic mineral nutrients including NH4+, K+, Mg2+ and soluble inorganic
      phosphate (Pi) were investigated to reveal the potential limiting nutrients for
      tannery sludge bioleaching process driven by Acidithiobacillus species, and the
      feasibility of supplementing the limiting nutrients to accelerate tannery sludge
      bioleaching was studied in the present study. It was found that the concentration
      of Pi was lower than 3.5 mg/L throughout the whole bioleaching process, which is
      the most probable restricting nutrient for tannery sludge bioleaching. Further
      experiments revealed that the deficiency of Pi could seriously influence the
      growth of Acidithiobacillus thiooxidans and lower its oxidization capacity for
      S0, and the limiting concentration of Pi for the growth of A. thiooxidans was 6
      mg/L. The low concentration of soluble Pi in sludge matrix was resulted from the
      extremely strong sorbing/binding capacity of tannery sludge for phosphate. The
      supplementation of more than 1.6 g/L KH2PO4 into tannery sludge bioleaching
      system could effectively stimulate the growth of Acidithiobacillus species,
      enhance Cr removal rate and further shorten tannery sludge bioleaching period
      from 10 days to 7 days. Therefore, inorganic phosphate supplementation is an
      effective and feasible method to accelerate tannery sludge bioleaching process,
      and the optimum dosage of KH2PO4 was 1.6 g/L for tannery sludge with 5.1% of
      total solids.

PMID- 21864882
TI  - New synthesis of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid and
      evaluation of the influence of adamantyl group on the DNA binding of a naphthoic
      retinoid.
AB  - 6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene(r)), a synthetic
      aromatic retinoid specific for RARbeta and RARgamma receptors, has been prepared
      utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4
      methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the
      position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of
      6-(4-methoxyphenyl)-2-naphthoic acid/ethyl ester and the 3-adamantyl analogs with
      DNA was studied in aqueous solution at physiological conditions by UV-vis
      spectroscopy. The calculated binding constants K(ligand-DNA) ranged between
      1.1*10(4) M(-1) and 1.1*10(5) M(-1), the higher values corresponding to those of
      the adamantylated compounds. Molecular modeling studies have emphasized that the
      intercalative binding of adapalene and its derivatives to DNA is mainly
      stabilized by hydrophobic interactions related to the presence of the adamantyl
      group.

PMID- 21864883
TI  - Heat shock protein 90 is a putative therapeutic target in patients with recurrent
      advanced-stage ovarian carcinoma with serous effusions.
AB  - Heat shock protein 90 (HSP90) has anti-apoptotic properties exerted through its
      cytoprotective function of chaperone activity and increased expression in
      response to stress. The present study analyzed the clinical role of HSP90 in
      effusions from patients with advanced-stage ovarian carcinoma. HSP90 protein
      expression was investigated in 265 effusions using immunohistochemistry. Results
      were analyzed for association with clinicopathologic parameters, including
      chemotherapy response and survival. The correlation between HSP90 and a panel of
      previously-studied antiapoptotic proteins was additionally investigated. HSP90
      was expressed in the cytoplasm and nucleus of tumor cells in 97% and 18% of
      specimens, respectively. Nuclear HSP90 expression was significantly higher in
      post-chemotherapy compared to pre-chemotherapy effusions (P = .005),
      significantly related to previous treatment with both platinol (P = .024) and
      paclitaxel (P = .007). Cytoplasmic HSP90 expression was significantly higher in
      effusions from patients with complete compared to incomplete/no response after
      second-line chemotherapy (P = .016). No association was found between HSP90
      expression and other clinicopathologic parameters or survival. Cytoplasmic HSP90
      expression was significantly associated with that of Bcl-2 in pre-chemotherapy
      effusions (P = .04), and marginally associated with cytoplasmic Survivin
      expression in post-chemotherapy effusions (P = .05). HSP90 is upregulated along
      tumor progression from primary diagnosis to recurrent effusion. HSP90 does not
      provide prognostic data in patients with advanced ovarian carcinoma effusions.
      However, HSP90 may be of predictive value as to who will benefit from treatment
      with HSP90 inhibitors to potentiate the effectiveness of platinol and paclitaxel
      in patients with recurrent advanced ovarian carcinoma effusions. We propose HSP90
      as a potential therapeutic target in this patient group.

PMID- 21864884
TI  - Consumption patterns and risk assessment of crab consumers from the Newark Bay
      Complex, New Jersey, USA.
AB  - The Newark Bay Complex (NBC) is a significant historical repository of
      polychlorinated dibenzodioxins (PCDDs) and dioxin-like compounds. Detection of
      high levels of 2,3,7,8 tetrachloro-dibenzodioxins (TCDD) and its toxicological
      equivalents in blue crabs in the early 1990's led to a ban on the taking and
      distribution of crabs from the NBC. Despite this ban and ongoing communication
      outreach, surveys of crabbers in 1995, 2002 and 2005 by the New Jersey Department
      of Environmental Protection (NJDEP) showed that crabbing for recreational
      purposes and for significant dietary supplementation was continuing. At the time
      they were surveyed, the crabbers had been consuming these crabs for an average of
      37% of their lives. Thus, exposure can be considered chronic. The surveys
      provided data on the duration, frequency and amount of NBC crab consumption. In
      2004, the NJDEP sampled blue crabs in the NBC and analyzed the edible portions
      for 2,3,7,8 TCDD toxicity equivalent (TEQ) concentration. We have combined the
      survey-based exposure data and the 2,3,7,8 TCDD TEQ concentration data to produce
      an estimate of the lifetime cancer risk to NBC crabbers from dioxin-like
      compounds. We employed a point-estimate approach using discrete lower, central
      tendency and reasonable maximum exposure (RME) estimates of exposure factors and
      a probabilistic approach to exposure factors. Both approaches show central
      tendency lifetime cancer risk of greater than one-in-a-thousand (10(-3)) and an
      upper percentile/RME risk of approximately one-in-a-hundred (10(-2)). Little
      extrapolation is involved in applying the 2,3,7,8-TCDD TEQ concentration data in
      crabs to risk estimates in the population consuming those crabs. The ongoing and
      frequent nature of the crab collection minimizes the uncertainty often inherent
      in food recall surveys. These estimates point to the continued risk posed to NBC
      crab consumers and to the continuing importance of this resource which, with
      proper remediation, could provide ongoing benefit to the surrounding community.

PMID- 21864885
TI  - Bioaccessibility of lead and arsenic in traditional Indian medicines.
AB  - Arsenic and lead have been found in a number of traditional Ayurvedic medicines,
      and the practice of Rasa Shastra (combining herbs with metals, minerals and
      gems), or plant ingredients that contain these elements, may be possible sources.
      To obtain an estimate of arsenic and lead solubility in the human
      gastrointestinal tract, bioaccessibility of the two elements was measured in 42
      medicines, using a physiologically-based extraction test. The test consisted of a
      gastric phase at pH 1.8 containing organic acids, pepsin and salt, followed by an
      intestinal phase, at pH 7 and containing bile and pancreatin. Arsenic speciation
      was measured in a subset of samples that had sufficiently high arsenic
      concentrations for the X-ray absorption near edge structure analysis used.
      Bioaccessible lead was found in 76% of samples, with a large range of
      bioaccessibility results, but only 29% of samples had bioaccessible arsenic. Lead
      bioaccessibility was high (close to 100%) in a medicine (Mahayograj Guggulu) that
      had been compounded with bhasmas (calcined minerals), including naga (lead)
      bhasma. For the samples in which arsenic speciation was measured, bioaccessible
      arsenic was correlated with the sum of As(V)-O and As(III)-O and negatively
      correlated with As-S. These results suggest that the bioaccessible species in the
      samples had been oxidized from assumed As-S raw medicinal ingredients (realgar,
      As(4)S(4), added to naga (lead) bhasma and As(III)-S species in plants).
      Consumption at recommended doses of all medicines with bioaccessibile lead or
      arsenic would lead to the exceedance of at least one standard for acceptable
      daily intake of toxic elements.

PMID- 21864886
TI  - A prospective, randomized trial of integrative medicine for women with ovarian
      cancer.
AB  - OBJECTIVES: Despite increased use of integrative medicine in cancer therapy,
      little data exist on its efficacy. This prospective, randomized, pilot trial
      sought to evaluate the feasibility of combined modality integrative medicine (CM
      IM) in women with ovarian cancer (OvCA) and evaluate its effects on quality of
      life (QoL), chemotherapy toxicity and immunologic profiles. METHODS: Women with
      newly diagnosed OvCA requiring chemotherapy were offered enrollment. Those
      randomized to the experimental arm received hypnosis, therapeutic massage and
      healing touch with each cycle of chemotherapy. The control arm received
      chemotherapy without CM-IM. All patients completed QoL questionnaires prior to
      cycles 1, 3 and 6, and 6-months after chemotherapy. Immunologic profiles were
      measured. Statistical analysis was based on intent-to-treat. Student's t-test and
      Fischer's exact-test were used to determine differences. RESULTS: Forty-three
      women enrolled. All women randomized to CM-IM were successfully treated. There
      were no statistical differences between the groups in age, stage, grade,
      histologic cell type, CA125 levels, or surgical cytoreductive status. There was
      no difference in overall QoL measurements. Re-hospitalization rates, treatment
      delays, anti-emetic use, and infection rates were similar. Immunologic profiles
      revealed no difference between arms for WBC or salivary IgA levels. Women
      receiving CM-IM had consistently higher levels of CD4, CD8 and NK cells, although
      this did not reach statistical significance. CONCLUSIONS: Prospective clinical
      evaluation of integrative medicine for women with gynecologic malignancy is
      feasible. This first, pilot study of CM-IM in gynecologic oncology demonstrated
      no improvement in QoL or chemotherapy toxicity. Integrative medicine-associated
      improvements in immunologic profiles warrant further investigation.

PMID- 21864887
TI  - GardasilTM HPV vaccination: surveillance of vaccine usage and adherence in a
      military population.
AB  - OBJECTIVES: To investigate the usage patterns and adherence rates with the
      quadrivalent HPV (qHPV) vaccine at Naval Medical Center San Diego. METHODS: This
      retrospective, cross-sectional study was conducted by using AHLTA (Electronic
      Health Record of DoD) to identify all qHPV recipients between 2006 and 2009.
      Charts were reviewed to extract demographic variables and immunization schedules
      for association analysis. Subjects were assigned intention-to-treat (ITT) if they
      initiated the series and reached the 1-year anniversary after dose-1 or in
      progress (IP) if the series was incomplete and within 1-year. ITT subjects were
      designated non-adherent or adherent based on 1-2 or 3 doses received. RESULTS:
      6792 females and 46 males with respective mean ages (years) of 19 (95% CI: 10-29)
      and 27 (95% CI: 9-46) initiated the qHPV series. The evaluable ITT population
      consisted of 5088 females and 31 males. The adherence rate for females was 32%
      (1656/5088) versus 3% (1/31) for males. For females, adherence declined from 45%,
      24%, to 14% with respect to increasing age: 8-17, 18-26, 27-50years. Adherence
      declined accordingly by beneficiary status: dependent daughters (43%), spouses
      (21%) and active duty (16%); and by clinic of vaccine initiation:
      Pediatrics/Adolescent (45%), Primary Care (38%), Immunization (21%), and OB/GYN
      (9%). Males were predominantly active duty 84%, vaccinated through immunization
      clinics 84%, and poorly adherent 3%. CONCLUSIONS: Optimal HPV immunization
      efficacy is derived from vaccine adherence and HPV naivety. This study of qHPV
      adherence has provided insight into real-world suboptimal use post-marketing.
      Usage patterns and adherence rates were significantly associated with demographic
      characteristics.

PMID- 21864888
TI  - Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a
      clinical and pathological evaluation.
AB  - OBJECTIVE: Endometrial cancer is classified into: Type I estrogen-dependent
      endometrioid adenocarcinoma, with good prognosis and type 2 non-estrogen
      dependent cancer with serous or clear cell histology and poor prognosis. Grade 3
      endometrioid cancers (G3 EEC), share features of type 1 and type 2 cancer and
      have not been classified as either. This study compares immunohistochemistry and
      survival in G3 EEC and type 2 cancers. METHODS: Clinicopathological data compared
      with immunohistochemistry and survival in 156 consecutive patients with poor
      prognosis cancer-G3 EEC, uterine papillary serous (UPSC) and clear cell carcinoma
      (CC), sarcoma, carcinosarcoma and endometrial tumors of mixed histology. 131
      (84%) datasets were complete, 25 tumors comprising sarcoma, carcinosarcoma or
      mixed histologies were excluded. Tissue microarray constructed and tested for
      estrogen receptor (ER), progesterone receptor (PR), p53 and human epidermal
      growth factor receptor-2 (Her-2). RESULTS: There was no significant difference in
      the mean age for G3 EEC (n=68) and USPC + CC (n=38), (68.01 and 67.08
      respectively, p=0.697) or stage at diagnosis (p=0.384). For ER, PR, p53 and Her
      2, there was no significant difference in marker positivity between G3 EEC and
      UPSC + CC (p=0.612, 0.132, 0.16 and 0.132 respectively). With a mean follow-up
      time 148 months Disease specific and recurrence-free survival between G3 EEC and
      USPC + CC was similar (p=0.842 and 0.863). CONCLUSION: G3 EEC and UPSC + CC share
      similar clinical, immunohistochemistry and poor survival. G3 EEC is better
      characterised as type 2 cancer and should be treated with similar adjuvant
      therapy to UPSC/CC.

PMID- 21864889
TI  - Evaluation of the Patient-Generated Subjective Global Assessment (PG-SGA) as a
      predictor of febrile neutropenia in gynecologic cancer patients receiving
      combination chemotherapy: a pilot study.
AB  - OBJECTIVE: Determine if pre-treatment Patient-Generated Subjective Global
      Assessment (PG-SGA) predicts febrile neutropenia (FN) in gynecologic cancer
      patients receiving primary combination chemotherapy. METHODS: Following IRB
      approval, clinicopathologic variables, pre-treatment laboratory values and PG-SGA
      were recorded from eligible patients. Bone marrow toxicity (CTC 3.0) divided
      groups of patients: (1) No grade 3 or 4 neutropenia, (2) grade 3 or 4
      neutropenia, (3) FN. Statistical analysis with Kruskal-Wallis one-way analysis of
      variance and a receiver operating characteristic (ROC) curve were performed.
      RESULTS: 58 patients met study inclusion: 25 in group 1, 28 in group 2, and 5 in
      group 3. Mean age was 61 and the majority, 42 (72%), had ovarian cancer. Median
      PG-SGA scores were: 6 (group 1) vs. 7 (group 2) vs. 14 (group 3) (p=0.019). Both
      median albumin: (1) 4.2 vs. (2) 4.0 vs. (3) 3.4 g/dl (p=0.041), and hemoglobin:
      (1) 12.1 vs. (2) 11.75 vs. (3) 10.6g/dl (p=0.05) differed between the groups. The
      overall AUC of the ROC curve for PG-SGA was 0.831 +/- 0.064 (95% CI=0.706 to
      0.956, p=0.015). Using the ROC, selecting a PG-SGA score of 7.5 to be predictive
      of febrile neutropenia yields a sensitivity of 100% and a specificity of 60%.
      When the cutoff value is set at 12.5, the specificity improves to 81% while
      decreasing sensitivity to 80%. CONCLUSIONS: PG-SGA scores were higher for
      patients experiencing FN and may be a reasonably predictive marker of FN in
      patients receiving multi-agent primary chemotherapy and likely benefactors of
      prophylactic GCSF.

PMID- 21864890
TI  - Are depictive gestures like pictures? commonalities and differences in semantic
      processing.
AB  - Conversation is multi-modal, involving both talk and gesture. Does understanding
      depictive gestures engage processes similar to those recruited in the
      comprehension of drawings or photographs? Event-related brain potentials (ERPs)
      were recorded from neurotypical adults as they viewed spontaneously produced
      depictive gestures preceded by congruent and incongruent contexts. Gestures were
      presented either dynamically in short, soundless video-clips, or statically as
      freeze frames extracted from gesture videos. In a separate ERP experiment, the
      same participants viewed related or unrelated pairs of photographs depicting
      common real-world objects. Both object photos and gesture stimuli elicited less
      negative ERPs from 400 to 600ms post-stimulus when preceded by matching versus
      mismatching contexts (dN450). Object photos and static gesture stills also
      elicited less negative ERPs between 300 and 400ms post-stimulus (dN300). Findings
      demonstrate commonalities between the conceptual integration processes underlying
      the interpretation of iconic gestures and other types of image-based
      representations of the visual world.

PMID- 21864892
TI  - The mechanically adaptive connective tissue of echinoderms: its potential for bio
      innovation in applied technology and ecology.
AB  - Echinoderms possess unique connective tissues, called mutable collagenous tissues
      (MCTs), which undergo nervously mediated, drastic and reversible or irreversible
      changes in their mechanical properties. Connective tissue mutability influences
      all aspects of echinoderm biology and is a key-factor in the ecological success
      of the phylum. Due to their sensitivity to endogenous or exogenous agents, MCTs
      may be targets for a number of common pollutants, with potentially drastic
      effects on vital functions. Besides its ecological relevance, MCT represents a
      topic with relevance to several applied fields. A promising research route looks
      at MCTs as a source of inspiration for the development of novel biomaterials.
      This contribution presents a review of MCT biology, which incorporates recent
      ultrastructural, biomolecular and biochemical analyses carried out in a
      biotechnological context.

PMID- 21864891
TI  - TMS suppression of right pars triangularis, but not pars opercularis, improves
      naming in aphasia.
AB  - This study sought to discover if an optimum 1 cm(2) area in the non-damaged right
      hemisphere (RH) was present, which could temporarily improve naming in chronic,
      nonfluent aphasia patients when suppressed with repetitive transcranial magnetic
      stimulation (rTMS). Ten minutes of slow, 1Hz rTMS was applied to suppress
      different RH ROIs in eight aphasia cases. Picture naming and response time (RT)
      were examined before, and immediately after rTMS. In aphasia patients,
      suppression of right pars triangularis (PTr) led to significant increase in
      pictures named, and significant decrease in RT. Suppression of right pars
      opercularis (POp), however, led to significant increase in RT, but no change in
      number of pictures named. Eight normals named all pictures correctly; similar to
      aphasia patients, RT significantly decreased following rTMS to suppress right
      PTr, versus right POp. Differential effects following suppression of right PTr
      versus right POp suggest different functional roles for these regions.

PMID- 21864894
TI  - Dendronized iron oxide nanoparticles for multimodal imaging.
AB  - The synthesis of small-size dendrons and their grafting at the surface of iron
      oxide nanoparticles were achieved with the double objective to obtain a good
      colloidal stability with a mean hydrodynamic diameter smaller than 100 nm and to
      ensure the possibility of tuning the organic coating characteristics including
      morphology, functionalities, physico-chemical properties, grafting of fluorescent
      or targeting molecules. Magnetic resonance and fluorescence imaging are then
      demonstrated to be simultaneously possible using such versatile superparamagnetic
      iron oxide nanocrystals covered by a dendritic shell displaying either
      carboxylate or ammonium groups at their periphery which could be further labelled
      with a fluorescent dye. The grafting conditions of these functionalized dendrons
      at the surface of SPIO NPs synthesized by co-precipitation have been optimized as
      a function of the nature of the peripheral functional group. The colloidal
      stability has been investigated in water and osmolar media, and in vitro and in
      vivo MRI and optical imaging measurements have been performed showing encouraging
      biodistribution.

PMID- 21864893
TI  - Engineering fibrin-binding TGF-beta1 for sustained signaling and contractile
      function of MSC based vascular constructs.
AB  - We present a strategy to conjugate TGF-beta1 into fibrin hydrogels to mimic the
      in vivo presentation of the growth factor in a 3D context. To this end, we
      engineered fusion proteins between TGF-beta1 and a bi-functional peptide composed
      of a Factor XIII domain and a plasmin cleavage site. In another version the
      protease cleavage site was omitted to examine whether the growth factor that
      could not be released from the scaffold by cells had different effects on tissue
      constructs. The optimal insertion site which yielded correctly processed,
      functional protein was found between the latency associated peptide and mature
      TGF-beta1 domains. In solution the fusion proteins exhibited similar biological
      activity as native TGF-beta1 as evidenced by inhibition of cell proliferation and
      promoter activity assays. Immunoprecipitation experiments demonstrated that the
      fusion TGF-beta1 protein bound to fibrinogen in a Factor XIII dependent manner
      and could be released from the peptide by the action of plasmin. In contrast to
      bolus delivery, immobilized TGF-beta1 induced sustained signaling in fibrin
      embedded cells for several days as evidenced by Smad2 phosphorylation. Prolonged
      pathway activation correlated with enhanced contractile function of vascular
      constructs prepared from hair follicle mesenchymal stem cells or bone marrow
      derived smooth muscle cells. Our results suggest that fibrin-immobilized TGF
      beta1 may be used to enhance the local microenvironment and improve the function
      of engineered tissues in vitro and potentially also after implantation in vivo
      where growth factor delivery faces overwhelming challenges.

PMID- 21864895
TI  - Functional hydrophobin-coating of thermally hydrocarbonized porous silicon
      microparticles.
AB  - Porous silicon (PSi) particles have been widely used in modulating the
      dissolution rate of various types of drugs loaded within its mesopores. This
      material can be surface treated in order to vary its hydrophobicity and several
      other properties, such as drug loading degree and release rate. Hydrophobins are
      a family of self-assembling proteins of fungal origin which have the ability to
      form layers on hydrophobic materials. This type of protein layer can modify the
      characteristics and control the binding properties of the surface on which it
      assembles. In this study, we have developed a procedure to coat thermally
      hydrocarbonized-PSi microparticles with hydrophobin II (HFBII) in order to modify
      the particles' hydrophobicity and to improve their biocompatibility, while
      maintaining intact the advantageous drug releasing properties of the PSi. The
      HFBII content adsorbed onto the particles was successfully quantified by a
      protein assay. Drug dissolution and permeation across Caco-2 cell monolayers were
      also conducted, together with viability studies in AGS, Caco-2 and HT-29 cells.
      The characterization and coating stability assessment showed that the HFBII
      coating desorbs partially from the particles' surface as the pH increases. The
      HFBII coating also improved the biocompatibility of the particles without
      compromising the enhanced drug permeation or release.

PMID- 21864896
TI  - Osteogenic evaluation of calcium/magnesium-doped mesoporous silica scaffold with
      incorporation of rhBMP-2 by synchrotron radiation-based MUCT.
AB  - The regenerative treatment of large osseous defects remains a formidable
      challenge in orthopedic surgery today. In the present study, we have synthesized
      biodegradable calcium/magnesium-doped silica-based scaffolds with hierarchically
      macro/mesoporous structure (CMMS), and incorporated recombinant human bone
      morphogenetic protein-2 (rhBMP-2) into the scaffolds to obtain a hybrid system
      for osteogenic factor delivery in the functional repair of bone defects. The
      developed CMMS/rhBMP-2 scaffolds presented interconnected porous network,
      macropores (200-500 MUm) and mesopores (5.7 nm), as well as good bioactivity and
      biocompatibility and proper degradation rate. Combined with the capacity to
      deliver ions and growth factors, the CMMS/rhBMP-2 scaffolds significantly
      promoted the in vitro osteogenic differentiation of bone marrow stromal cells
      (bMSCs), as evidenced by the enhanced expression of Runx-2, osteopontin,
      osteocalcin and bone sialoprotein, and induced the ectopic bone formation in the
      thigh muscle pouches of mice. We further assessed the in vivo effects of
      CMMS/rhBMP-2 scaffolds in a rabbit femur cavity defect model by using synchrotron
      radiation-based MUCT (SRMUCT) imaging and histological analysis, indicating that
      the CMMS/rhBMP-2 scaffolds resulted in more bone regeneration compared to that
      observed with the CMMS scaffolds without rhBMP-2. Moreover, scaffolds with or
      without rhBMP-2 underwent gradual resorption and replacement with bone and almost
      disappeared at 12 weeks, while the dense CMMS/rhBMP-2 material showed slower
      degradation rate and promoted the least extensive neo-bone formation. This study
      suggested that the hybrid CMMS/rhBMP-2 scaffolds system demonstrates promise for
      bone regeneration in clinical case of large bone defects.

PMID- 21864897
TI  - Subtleties of biomineralisation revealed by manipulation of the eggshell
      membrane.
AB  - Biocalcification of collagen matrices with calcium phosphate and
      biosilicification of diatom frustules with amorphous silica are two discrete
      processes that have intrigued biologists and materials scientists for decades.
      Recent advancements in the understanding of the mechanisms involved in these two
      biomineralisation processes have resulted in the use of biomimetic strategies to
      replicate these processes separately using polyanionic, polycationic or
      zwitterionic analogues of extracellular matrix proteins to stabilise amorphous
      mineral precursor phases. To date, there is a lack of a universal model that
      enables the subtleties of these two apparently dissimilar biomineralisation
      processes to be studied together. Here, we utilise the eggshell membrane as a
      universal model for differential biomimetic calcification and silicification. By
      manipulating the eggshell membrane to render it permeable to stabilised mineral
      precursors, it is possible to introduce nanostructured calcium phosphate or
      silica into eggshell membrane fibre cores or mantles. We provide a model for
      infiltrating the two compartmental niches of a biopolymer membrane with different
      intrafibre minerals to obtain materials with potentially improved structure
      property relationships.

PMID- 21864898
TI  - Anisotropic cell sheets for constructing three-dimensional tissue with well
      organized cell orientation.
AB  - Normal human dermal fibroblasts were aligned on micropatterned thermoresponsive
      surfaces simply by one-pot cell seeding. After they proliferated with maintaining
      their orientation, anisotropic cell sheets were harvested by reducing temperature
      to 20  degrees C. Surprisingly, the cell sheets showed different shrinking rates
      between vertical and parallel sides of the cell alignment (aspect ratio: approx.
      3: 1), because actin fibers in the cell sheets were oriented with the same
      direction. The control of cell alignment provided not only a physical anisotropy
      but also biological impacts to the cell sheet. Vascular endothelial growth factor
      (VEGF) secreted by aligned fibroblasts was increased significantly, whereas
      transforming growth factor-beta1 (TGF-beta1) expression was the same level in
      anisotropic cell sheets as cell sheets having random cell orientations.
      Furthermore, although the amount of deposited type I collagen was different non
      significantly onto between cell sheets with and without controlled cell
      alignment, collagen deposited onto fibroblasts sheets with cell alignment also
      showed anisotropy, verified by a fluorescence imaging analysis. The physical and
      biological anisotropies of cell sheets were potentially useful to construct
      biomimetic tissues that were organized by aligned cells and/or extracellular
      matrix (ECM) including collagen in cell sheet-based regenerative medicine.
      Furthermore, due to the unique thermoresponsive property, the anisotropic cell
      sheets were successfully manipulated using a gelatin-coated plunger and were
      layered with maintaining their cell alignment. The combined use of the
      anisotropic cell sheet and cell sheet manipulation technique promises to create
      complex tissue that requires the three-dimensional control of their anisotropies,
      as one of the next-generation cell sheet technologies.

PMID- 21864899
TI  - The pivotal role of fibrocytes and mast cells in mediating fibrotic reactions to
      biomaterials.
AB  - Almost all biomaterial implants are surrounded by a fibrotic capsule, although
      the mechanism of biomaterial-mediated fibrotic reactions is mostly unclear. To
      search for the types of cells responsible for triggering the tissue responses, we
      used poly-L glycolic acid polymers capable of releasing various reagents. We
      first identified that CD45(+)/Collagen 1(+) fibrocytes are recruited and resided
      within the fibrotic capsule at the implant interface. Interestingly, we found
      that the recruitment of fibrocytes and the extent of fibrotic tissue formation
      (collagen type I production) were substantially enhanced and reduced by the
      localized release of compound 48/80 and cromolyn, respectively. Since it is well
      established that compound 48/80 and cromolyn alter mast cell reactions, we
      hypothesized that mast cells are responsible for triggering fibrocyte recruitment
      and subsequent fibrotic capsule formation surrounding biomaterial implants. To
      directly test this hypothesis, similar studies were carried out using mast cell
      deficient mice, WBB6F1/J-Kit(W)/Kit(W-v)/, and their congenic controls. Indeed,
      mast cell deficient mice prompted substantially less fibrocyte and myofibroblast
      responses in comparison to C57 wild type mice controls. Most interestingly,
      subcutaneous mast cell reconstitution of WBB6F1/J-Kit(W)/Kit(W-v)/J mice almost
      completely restored the fibrocyte response in comparison to the C57 wild type
      response. These results indicate that the initial biomaterial interaction
      resulting in the stimulation of mast cells and degranulation byproducts not only
      stimulates the inflammatory cascade but significantly alters the downstream
      fibrocyte response and degree of fibrosis.

PMID- 21864900
TI  - Fluorophore-labeled nanocapsules displaying IgG Fc-binding domains for the
      simultaneous detection of multiple antigens.
AB  - Simultaneous detection of multiple antigens by conventional immunological methods
      has been limited by the source of primary antibodies. Each antibody should be
      derived from a different host species (or subclass of immunoglobulin (Ig)) for
      suppressing the cross-reactions of secondary antibodies. Here we describe an
      innovative method for simultaneous, rapid, and sensitive detection of multiple
      antigens using ~30-nm bio-nanocapsules (BNCs) displaying IgG Fc-binding Z domains
      derived from Staphylococcus aureus protein A (ZZ-BNC). When Cy2-labeled ZZ-BNC
      (Cy2-ZZ-BNC) was used instead of Cy2-labeled secondary antibody in western blot
      analysis, both sensitivity and signal intensity were significantly increased. The
      complex of Cy5-ZZ-BNC and mouse IgG2a (which shows moderate affinity to the Z
      domain) was not dissociated, even in the presence of 8-fold excess of free mouse
      IgG2a. In addition, crosslinking with BS(3) (bis-sulfosuccinimidyl suberate)
      efficiently stabilized the interaction. The ZZ-BNCs labeled with various Cy dyes
      facilitated the simultaneous detection of multiple antigens using primary
      antibodies derived from the same host species, by western blot analysis,
      immunocytochemistry and flow cytometry, which could expand the possibility of bio
      imaging probes in various immunofluorescence techniques.

PMID- 21864901
TI  - Intracellular delivery of paclitaxel using oil-free, shell cross-linked HSA-
      multi-armed PEG nanocapsules.
AB  - Various approaches to increase the solubility of water-insoluble anti-cancer
      drugs in aqueous formulations have been undertaken with the aim of treating solid
      tumors through intravenous drug administration. Nanoscale drug carriers are
      particularly attractive for cancer therapy because of their passive targeting
      effect to enhance the therapeutic efficacy of drugs. Here we introduce an oil
      free, shell cross-linked nanocapsule as an efficient intracellular delivery
      system for paclitaxel. The nanocapsules are prepared by emulsifying amine
      reactive six-arm-branched polyethylene glycol (PEG) in dichloromethane into
      aqueous solution of human serum albumin (HSA), followed by cross-linking at the
      organic/aqueous interface. Paclitaxel is successfully incorporated into the
      HSA/PEG nanocapsules having a spherical shape with an average diameter of about
      280 nm. In several types of cells, the surface modification of nanocapsules with
      a cell-penetrating peptide, Hph1, greatly facilitates cellular uptake and
      apoptosis-inducing effects of paclitaxel. Furthermore, the targeted anti-tumor
      activities of the paclitaxel-loaded nanocapsules in a mouse tumor model suggest
      that the shell cross-linked nanocapsules are very promising oil-free nanoscale
      delivery vehicles for water-insoluble anti-cancer agents.

PMID- 21864902
TI  - Computational design principles for bioactive dendrimer based constructs as
      antagonists of the TLR4-MD-2-LPS complex.
AB  - The cell surface interaction between bacterial lipopolysaccharide (LPS), Toll
      like receptor 4 (TLR4) and MD-2 is central to bacterial sepsis syndromes and
      wound healing. We have shown that a generation (G) 3.5 polyamidoamine (PAMAM)
      dendrimer that was partially glycosylated with glucosamine inhibits TLR4-MD-2-LPS
      induced inflammation in a rabbit model of tissue scaring. However, it was a
      mixture of closely related chemical species because of the polydispersity of the
      starting PAMAM dendrimer. Generation 2 triazine dendrimers with single chemical
      entity material status are available at low cost and at the kilogram scale. PAMAM
      dendrimer can be synthetically grafted onto this triazine core dendrimer to make
      new triazine-PAMAM hybrid dendrimers. This led us to examine whether molecular
      modelling methods could be used to identify the key structural design principles
      for a bioactive lead molecule that could be synthesized and biologically
      evaluated. We describe our computer aided molecular studies of several dendrimer
      based constructs and the key design principles identified. Our approach should be
      more broadly applicable to the biologically focused, rational and accelerated
      design of molecules for other TLR receptors. They could be useful for treating
      infectious, inflammatory and malignant diseases.

PMID- 21864903
TI  - The reversal of cisplatin-induced nephrotoxicity by selenium nanoparticles
      functionalized with 11-mercapto-1-undecanol by inhibition of ROS-mediated
      apoptosis.
AB  - Although cisplatin is still one of the most effective chemotherapy agents for
      human cancers, its clinical use is limited by serious side effects, especially
      nephrotoxicity. Oxidative stress is an important mediator of cisplatin-induced
      nephrotoxicity. In the present study, a simple method for functionalization of
      selenium nanoparticles by self-assembly of 11-mercapto-1-undecanol (Se@MUN) to
      achieve enhanced antioxidant activity and antagonis against cisplatin-induced
      nephrotoxicity has been demonstrated. The chemical structure of the nanoparticles
      was characterized by various microscopic and spectroscopic methods. The results
      revealed that the spherical nanoparticles were capped with MUN on the surface
      through formation of Se-S bond. The in vitro protective effects of Se@MUN on HK-2
      proximal tubular cells against cisplatin-induced nephrotoxicity and the
      underlying mechanisms were also investigated. Se@MUN exhibited free radical
      scavenging activity and higher cellular uptake in human normal cells by comparing
      with SeNPs. Se@MUN significantly attenuated cisplatin-induced reduction in cell
      viability, appearance of Sub-G1 peak, nuclear condensation and DNA fragmentation
      in HK-2 cells. Activation of caspase-3 in cells exposed to cisplatin was also
      effectively blocked by Se@MUN. Moreover, Se@MUN significantly prevented the
      cisplatin-induced overproduction of intracellular ROS. Our findings suggest that
      Se@MUN is a promising selenium species with potential application in prevention
      of cisplatin-induced renal injury.

PMID- 21864904
TI  - Correlation between cord insertion type and superficial choriovasculature in
      diamniotic-monochorionic twin placentas.
AB  - BACKGROUND: Non-central cord insertion has been associated with diminished
      chorionic vascular distribution in singleton placentas. The choriovascular
      correlates of peripheral cord insertion in diamniotic-monochorionic twin
      placentas remain undetermined. AIM: To study the association between type of cord
      insertion and choriovascular distribution of both twin territories in diamniotic
      monochorionic twin placentas. DESIGN: A prospective cohort of 138 monochorionic
      placentas was examined at Women and Infants Hospital between 2009 and early 2011.
      Thirty-five cases (25%), including disrupted placentas, placentas from higher
      order multiples and placentas from pregnancies complicated by twin-to-twin
      transfusion syndrome, were excluded. The correlation between cord insertion type
      and superficial choriovascular distribution was studied in the remaining 103 dye
      injected diamniotic-monochorionic placentas. Cord insertion was categorized as
      paracentral, marginal or velamentous. The choriovascular distribution of each
      individual twin territory was assessed by analysis of number and density (number
      per surface area) of perforating chorionic arteries (PCA). RESULTS: In contrast
      with singleton placentas, there was no correlation between cord insertion type
      and a twin's own choriovascular distribution in diamniotic-monochorionic
      placentas. However, a strong correlation was found between the choriovascular
      distribution of one twin and the cord insertion type of the opposite twin. For a
      twin with paracentral or marginal cord insertion, the PCA density was
      significantly higher if the co-twin had a velamentous cord insertion than if the
      co-twin had a paracentral cord insertion (P < 0.001 and P < 0.05, respectively).
      Similarly, the PCA density of a twin with velamentous cord insertion tended to be
      higher if the co-twin had a velamentous, rather than paracentral cord insertion
      (P = 0.09). CONCLUSIONS: This is the first study to suggest that in diamniotic
      monochorionic twin gestations, the choriovascular architecture correlates with
      the cord insertion type of the co-twin. In general, velamentous cord insertion is
      associated with expanded choriovascular distribution in the opposite twin
      territory. Our observations may reflect novel manifestations of twin
      interdependence in monochorionic pregnancies.

PMID- 21864905
TI  - Effects of carbofuran on the sea bass (Dicentrarchus labrax L.): study of
      biomarkers and behaviour alterations.
AB  - The objective of this study was to investigate the acute effects of the pesticide
      carbofuran on the sea bass (Dicentrarchus labrax) using parameters at different
      levels of biological organisation (swimming behaviour and several biomarkers) and
      possible relationships between alterations found in different effect criteria. In
      a bioassay, sea bass juveniles were individually exposed to different doses of
      carbofuran (31, 63, 125 and 250 MUg/L) for 96 h. At the end of the bioassay, the
      swimming performance and 11 biomarkers were determined. Biomarkers were:
      hepatosomatic index (HSI), lipid peroxidation (LPO), reduced glutathione and the
      activities of the enzymes ethoxyresorufin O-deethylase (EROD), glutathione S
      transferases, superoxide dismutase, catalase, glutathione peroxidase, glutathione
      reductase, brain acetylcholinesterase (AChE) and muscle cholinesterases (ChE).
      After 96 h of exposure, carbofuran induced a decrease of the swimming velocity
      and inhibition of EROD activity at all concentrations tested, and inhibition of
      muscle ChE and brain AChE activities at 250 MUg/L. No relevant alterations in any
      of the other tested parameters were found. These results show that carbofuran
      induced adverse effects on fish by interfering with neurofunction, capability of
      detoxication and swimming velocity. In addition, positive and significant
      correlations between the swimming velocity and (i) brain AChE activity, (ii)
      muscle ChE activity and (iii) EROD activity suggest that the inhibition of these
      enzymes may somehow be related to the behavioural changes observed. Since these
      functions are determinant for the survival and performance of the fish in the
      wild, the findings of the present study suggest that adverse effects may occur in
      populations exposed to carbofuran if a sufficient number of animals is affected.

PMID- 21864906
TI  - Redox imbalance in rat tissues exposed with organophosphate pesticides and
      therapeutic potential of antioxidant vitamins.
AB  - Organophosphate pesticides are among the most widely used synthetic chemicals for
      controlling domestic and agricultural pests. Present study was aimed to evaluate
      the potential of chlorpyrifos, parathion and malathion, to disturb glutathione
      homeostasis in rat tissues and to find out whether the pre-feeding of antioxidant
      vitamins has some ameliorating effect on the pesticide-induced alterations. The
      results showed that these pesticides, alone or in combination, caused decrease in
      the levels of GSH and the corresponding increase in the levels of GSSG,
      decreasing the GSH/GSSG ratio. The results also showed NADPH/NADP(+) and
      NADH/NAD(+) ratios were also decreased in the rat tissues on pesticide exposure.
      These pesticides, alone or in combination, caused increase in the activities of
      glutathione reductase and glucose-6-phosphate dehydrogenase in all the rat
      tissues studied. The findings show that these pesticides generate oxidative
      stress and prior feeding of mixture of antioxidant vitamins tend to reduce the
      toxicities of these pesticides.

PMID- 21864907
TI  - Pharmacokinetic comparison of controlled- and immediate-release formulations of
      dexibuprofen after single and multiple oral doses in fasting healthy male Korean
      volunteers.
AB  - BACKGROUND: Dexibuprofen is a pure S(+)-enantiomer product of racemic ibuprofen.
      A new extended-release form of dexibuprofen has recently been developed.
      OBJECTIVE: We aimed to compare pharmacokinetic characteristics of controlled
      release (CR) and immediate-release (IR) formulations of dexibuprofen after single
      and multiple oral doses in fasting healthy male Korean volunteers. METHODS: Both
      single- and multiple-dose studies used an open-label, randomized, 2-way,
      crossover design. In the single-dose study, 24 subjects were administered a 600
      mg CR or 300-mg IR formulation. In the multiple-dose study, 24 subjects were
      administered a 600-mg CR formulation q12h or 300-mg IR formulation q6h.
      Pharmacokinetic parameters of dexibuprofen were determined by noncompartmental
      analysis. RESULTS: All formulations used in the single- and multiple-dose studies
      were well tolerated, and there were no severe adverse events. In the single-dose
      study, the mean (SD) AUC(0-t) was 155.60 (40.94) MUg/h/mL for the CR formulation
      and 161.11 (37.50) MUg/h/mL for the IR formulation; the mean (SD) C(max) values
      were 22.71 (6.64) and 23.77 (4.91) MUg/mL, respectively; and the median T(max)
      values were 2.01 hours and 2.00 hours, respectively. The geometric mean ratios
      (90% CI) of the CR to IR formulations were 0.96 (0.92-1.00) for AUC(0-t) and 1.00
      (0.87-1.14) for C(max). In the multiple-dose study, the mean (SD) AUC(0-tau)
      values for CR and IR were 129.70 (23.72) MUg/h/mL and 150.04 (27.09) MUg/h/mL,
      respectively; the mean (SD) C(max,ss) values were 24.51 (5.12) and 21.69 (5.21)
      MUg/mL, respectively; and the median T(max.ss) values were 2.51 hours and 5.25
      hours, respectively. The geometric mean ratios (90% CI) of the CR to IR
      formulations were 0.86 (0.81-0.91) for AUC(0-tau) and 1.13 (1.03-1.24) for
      C(max). CONCLUSIONS: The pharmacokinetic parameters of single and multiple
      administrations of dexibuprofen did not differ for the IR and CR formulations in
      this small, selected group of healthy male Korean subjects. Both formulations
      were well tolerated.

PMID- 21864908
TI  - Efficacy and tolerability of nebivolol in stage I-II hypertension: a pooled
      analysis of data from three randomized, placebo-controlled monotherapy trials.
AB  - BACKGROUND: Nebivolol is a beta(1)-selective beta-blocker with NO-mediated
      vasodilatory properties, approved in the United States for the treatment of stage
      I-II hypertension. OBJECTIVE: The purpose of this pooled analysis was to
      summarize efficacy and provide a brief overview of the tolerability associated
      with the use of nebivolol. METHODS: PubMed was searched for randomized, double
      blind, placebo-controlled, parallel-group trials of monotherapy with nebivolol
      for stage I-II hypertension of at least 12 weeks' duration. This article reports
      pooled changes in sitting diastolic blood pressure (DBP), systolic blood pressure
      (SBP), and heart rate (HR) at trough; proportions of responders (patients whose
      end-point sitting DBP at trough was <90 mm Hg or whose sitting DBP at trough had
      decreased from baseline by <=10 mm Hg); and the most frequent adverse events
      (AEs). These data were also summarized in the subpopulation of black patients.
      RESULTS: The literature search yielded 3 similarly designed studies. In all 3
      trials, a single-blind placebo run-in phase (4-6 weeks) was followed by
      randomization (baseline) and a 12-week double-blind treatment phase in which
      patients received nebivolol 1.25 to 30 or 40 mg/d or placebo. The primary
      efficacy measure in all 3 trials was the mean change from baseline in sitting DBP
      at 12 weeks, based on the intent-to-treat population. In the pooled sample, 930
      (46.1%) patients were women, and the mean age was 53.6 years. Compared with
      placebo (n = 205), the reductions in DBP (up to 11.1 mm Hg), SBP (up to 12.4 mm
      Hg), and HR (up to 9.2 beats/min) were significantly greater with nebivolol (n =
      1811) at the recommended dosages of 5-30/40 mg/d (all, P < 0.001). The most
      commonly reported AEs were headache (nebivolol, all dosages, 7.1%; placebo,
      5.9%), fatigue (3.6% vs 1.5%, respectively), and nasopharyngitis (3.1% vs 4.4%).
      The efficacy and tolerability of nebivolol in black patients were similar to
      those observed in the total study population. CONCLUSION: Based on the pooled
      results from the 3 monotherapy trials reported here, nebivolol administered for
      12 weeks was efficacious and generally well tolerated in patients with stage I-II
      hypertension.

PMID- 21864910
TI  - Health risks of dietary exposure to perfluorinated compounds.
AB  - Perfluorinated compounds (PFCs) form a diverse group of chemicals with surface
      active properties manufactured for over 50 years. In recent years, a number of
      studies have reported the ubiquitous distribution of PFCs in human tissues and
      wildlife. Although the relative importance of the routes of human exposure to
      these compounds is not well established yet, it has been suggested that food
      intake and packaging, water, house dust, and airborne are all potentially
      significant sources. However, dietary intake is probably the main route of
      exposure to these compounds, including perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA), the most extensively investigated PFCs. This paper
      reviews the state of the science regarding the concentrations of PFCs in
      foodstuffs, human dietary exposure to these compounds and their health risks. The
      influence of processing, cooking and packaging on the PFCs levels in food is also
      discussed. Because of the rather limited information about human dietary
      exposure, studies to determine exposure to PFCs through the diet for the general
      population of a number of countries are clearly necessary. The correlation of
      PFCs body burdens and dietary intake of PFCs should be also established.

PMID- 21864909
TI  - Pedagogy of individual choice and female inmate reentry in the U.S. Southwest.
AB  - Much of the mental health, substance use, and educational programming within a
      particular women's prison in the southwestern United States promotes individual
      choice and agency. Incarcerated women from rural areas are told that their
      ability to succeed outside of prison is primarily dependent upon their personal
      choices. Comparably little attention is given to preparing women for their
      upcoming release or to overcoming structural barriers that could undermine
      successful reentry within rural communities. As a result, these returning
      citizens, many of whom grapple with mental illness and alcohol or drug
      dependence, blame themselves for their inability to surmount these barriers. In
      this qualitative research, we draw upon the perspectives of 99 incarcerated women
      to clarify how ideologies of individual choice promulgated in reentry pedagogy
      clash with contextual factors within rural communities to derail the reentry
      process. We also consider community reentry from Amartya Sen's capabilities
      framework and discuss how this model could inform needed interventions.

PMID- 21864911
TI  - SERPING1 mutations in 59 families with hereditary angioedema.
AB  - Hereditary angioedema due to C1 Inhibitor (C1Inh) deficiency (HAE types I and II)
      is a rare, life-threatening disease causing spontaneous edema of the submucosal
      layers. A cohort of 127 individuals with symptoms of recurrent familial
      angioedema from 59 non-related families was studied. All the patients included
      fulfilled the diagnostic and biochemical criteria of HAE, including low C1Inh
      function and/or concentration. Genetic studies were carried out by PCR and
      sequencing of the C1NH locus followed, in the negative cases, by MLPA, long-range
      PCR and restriction enzyme analysis of genomic DNA to detect potential large
      rearrangements. Mutations located in consensus splicing sequences or nearby
      positions were studied by RT-PCR. The study identified 52 different mutations (25
      missense, 15 frameshift, 7 splicing defects and 5 large deletions) responsible
      for the disease in 56 HAE families. In the remaining three families no molecular
      alteration could be detected. Twenty-seven of the mutations in this cohort are
      novel and 10 are confirmed de novo cases. The pathologic effect of the 5 splicing
      defects first reported here was assessed at the RNA and protein levels. Large
      deletions affecting exons 4 and 7, ranging from approximately 1500 to 2500 bp,
      were partially characterized by their altered restriction patterns upon long
      range amplification. These results highlight the heterogeneity of mutations in
      the C1NH gene causing C1Inh deficiency and HAE. An approach to the molecular
      effects associated to each of the mutations reported here was made when possible
      based on the available data of pathological variants of serpins.

PMID- 21864912
TI  - Symptomatic subsyndromal depression in hospitalized hypertensive patients.
AB  - BACKGROUND: Clinicians generally agree on the association between depression and
      hypertension. Less clear is if the nature of the link is direct or indirect and
      if this should be considered confined only to syndromal forms or if it concerns
      also subsyndromal affective presentations. This study investigated the nature of
      the association between hypertension and subsyndromal depression in hospitalized
      hypertensive patients. METHODS: 196 hypertensive and 96 non hypertensive
      inpatients underwent a SCID interview, to exclude patients positive for any Axis
      I or Axis II diagnosis. Symptomatic Subsyndromal Depression (SSD) was identified
      according to criteria proposed by Judd. Psychopathological assessment was
      performed with Anxiety Sensitivity Index (ASI) and Hopkins Symptom Checklist-90
      (SCL-90). Clinical assessments included blood pressure measurement, evaluation of
      general health conditions and screening cardiovascular risk factors (smoke,
      alcohol, body weight, sedentary life style). RESULTS: Hypertensives met more
      frequently criteria for SSD. They also scored higher on ASI and SCL-90. However,
      those with more severe physical conditions, if compared with more healthy
      patients, did not show increased psychopathological severity. Similarly,
      psychopathological symptom severity did not differ among hypertensives positive
      for other cardiovascular risk factors, commonly more frequent among depressed
      subjects. LIMITATIONS: Further analyses are needed to explore the potential
      advantage obtained on blood pressure control by treating SSD. CONCLUSIONS:
      Hospitalized hypertensives, more frequently satisfied criteria for Symptomatic
      Subsyndromal Depression. These milder affective forms are probably directly
      linked to the presence of hypertension, rather than being indirectly associated
      to physical impairment or to higher prevalence of other cardiovascular risk
      factors.

PMID- 21864913
TI  - Flourishing or floundering? Prevalence and correlates of anxiety and depression
      among a population-based sample of adult cancer survivors 6months after
      diagnosis.
AB  - OBJECTIVE: To describe the prevalence of anxiety, depression and comorbid anxiety
      depression among adult cancer survivors six months following diagnosis, and
      identify the individual, disease, health behaviour, psychological and social
      factors associated with psychological morbidity. METHODS: A population-based
      sample of adult cancer survivors was recruited from two state-based cancer
      registries in Australia. Data for 1323 survivors were obtained by self-report
      questionnaire and linkage with registry data. Anxiety and depression were
      assessed by the 14-item Hospital Anxiety and Depression Scale (HADS). RESULTS:
      The prevalence of psychological morbidity was 28% (95% CI: 23%-33%).
      Specifically, 24% (95% CI: 19%-29%) of survivors were identified as cases on
      anxiety (irrespective of depression), 14% (95% CI: 9%-19%) as cases on depression
      (irrespective of anxiety) and 10% (95% CI: 5%-15%) as cases on comorbid anxiety
      depression. In addition to mental health history prior to cancer, modifiable
      health behaviours (physical activity, smoking status), psychological
      (helplessness-hopelessness, anxious preoccupation coping) and social (low
      positive social interaction) characteristics were stronger indicators of
      psychological morbidity than survivors' individual or disease characteristics.
      LIMITATIONS: Psychological morbidity was assessed by self-report screening
      instrument rather than clinical interview. The extent to which psychological
      morbidity is age-related versus cancer-related cannot be determined without a
      gender- and age-matched control group. CONCLUSION: Although lower than previously
      reported, psychological morbidity is prevalent six months after a cancer
      diagnosis and emphasises the need for routine psychosocial assessment throughout
      the cancer trajectory to identify those at increased risk or in need of immediate
      intervention. Physical activity, smoking cessation and coping skills training
      interventions warrant further exploration.

PMID- 21864914
TI  - A comparison of three screening tools to identify perinatal depression among low
      income African American women.
AB  - BACKGROUND: The purpose of the current study was to determine the sensitivity,
      specificity, and positive predictive value of three depression screening tools
      among a low-income African American population of pregnant and recently delivered
      women enrolled in home visitation programs in a low-income urban community.
      METHODS: Ninety-five women enrolled in home visitation programs-32 who were
      pregnant and 63 with a child <6 months comprise the study sample. Each woman
      completed a structured clinical interview and three depression screening tools
      the Edinburgh Postnatal Depression Scale (EPDS), Center for Epidemiologic Studies
      Depression Scale (CES-D), and Beck Depression Inventory II (BDI-II). RESULTS:
      Over a quarter of women (28.4%) were experiencing major depression. Each
      screening tool was highly accurate in detecting major depression and major or
      minor depression among prenatal and postpartum women, with areas under the curve
      (AUCs) >0.90. Sensitivities of all screening tools were improved when using
      cutoffs lower than those considered standard by instrument developers.
      LIMITATIONS: Participants were recruited from home visitation programs in an
      urban context which may limit generalizability to other populations of low-income
      African American women. Given that no women during pregnancy met criteria for
      minor depression, it was not possible to determine optimal prenatal cutoff
      scores. CONCLUSIONS: Three depression screening tools-the EPDS, CES-D, and BDI-II
      appear to be reliable and brief assessments of major and minor depression among
      low-income African American perinatal women. Providers using these tools should
      consider using lower cutoff scores to most effectively identify women in need of
      depression treatment.

PMID- 21864915
TI  - Psychobiological aspects of somatization syndromes: contributions of inflammatory
      cytokines and neopterin.
AB  - Previous research suggests a dysregulation of immune-to-brain communication in
      the pathophysiology of somatization syndromes (multiple somatoform symptoms). We
      compared blood levels of the inflammatory markers tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and
      neopterin between 23 patients with somatization syndromes (Somatoform Symptom
      Index-8, SSI-8), 23 age- and sex-matched healthy controls and 23 patients with
      major depression. No group differences were found for IL-1ra and IL-6. While TNF
      alpha was increased in both clinical groups, neopterin was only increased in
      somatization syndromes. Correlational analyses revealed that neopterin tended to
      be related to somatoform pain complaints in patients with somatization syndromes.
      This study is the first to demonstrate increased levels of TNF-alpha and
      neopterin in patients with somatization syndromes without a diagnosis of
      depression, which may support a role of immune alterations in somatization
      syndromes. Neopterin is a reliable indicator for interferon-gamma (IFN-gamma)
      which was identified as the only cytokine that induces significant production of
      neopterin. Considering recent research indicating that IFN-gamma can lead to
      increased neuronal responsiveness and body perceptions by reducing inhibitory
      tone in the dorsal horn, the observed association between somatization syndromes
      and neopterin might support the idea of central sensitization in the pathogenesis
      of somatoform symptoms.

PMID- 21864916
TI  - Cardiac troponin-T and the prediction of acute and long-term mortality after
      acute pulmonary embolism.
AB  - BACKGROUND: Although cardiac troponin elevation during acute pulmonary embolism
      (PE) predicts in-hospital death, its long-term prognostic significance, and the
      role of troponin-T concentration in this prediction, is unknown. Moreover, its
      use in acute PE in elderly populations with multiple comorbidities is not well
      described. METHODS: Consecutive patients presenting with confirmed PE to a
      tertiary hospital between 2000 and 2007 with troponin-T measured were identified
      retrospectively and their outcomes tracked from a state-wide death registry.
      RESULTS: There were 577 patients, (47% male) with a mean age (+/- standard
      deviation) of 70.1 +/- 15.2 years, of whom 19 died during index admission. Of the
      558 patients who survived to discharge, 186 patients died during a mean follow-up
      of 3.8 +/- 2.4 years. There were 187 (32%) patients with elevated troponin-T (>=
      0.01 MUg/L). Troponin-T concentration was significantly and independently
      associated with in-hospital and long-term mortality whether analyzed as a
      continuous or categorical variable (p<0.001). However, different cut-points were
      required to optimally predict in-hospital and post-discharge long-term mortality
      in multivariate analysis. Troponin-T >= 0.01 MUg/L was not an independent
      predictor of in-hospital or post-discharge survival. A cut-point of troponin-T >=
      0.03 MUg/L was required to independently predict in-hospital death (p=0.03), and
      troponin-T >= 0.1 MUg/L was required to independently predict long-term mortality
      (hazard ratio 2.3, 95% confidence interval 1.4-3.8, p=0.001). CONCLUSIONS:
      Troponin-T elevation during acute PE shows a concentration-dependent relationship
      with acute and long-term outcome. Concentrations of troponin-T well above the
      threshold for detection may be required to independently contribute to prediction
      of outcome in elderly populations with acute PE.

PMID- 21864917
TI  - Three-year follow-up of the MULTIcentre evaluation of Single high-dose Bolus
      TiRofiban versus Abciximab with Sirolimus-eluting STEnt or Bare-Metal Stent in
      Acute Myocardial Infarction StudY (MULTISTRATEGY).
AB  - BACKGROUND: The Multicentre Evaluation of Single high-dose Bolus TiRofiban versus
      Abciximab with Sirolimus-eluting Stent or Bare Metal Stent in Acute Myocardial
      Infarction Study [MULTISTRATEGY]) randomised 745 patients with ST-elevation
      myocardial infarction to receive high-dose bolus (HDB) tirofiban or abciximab
      infusion and sirolimus-eluting (SES) or uncoated-stent (BMS) implantation.
      Tirofiban was non-inferior to abciximab in terms of ST-segment resolution after
      intervention, whereas 8 month-major adverse cardiac events occurred in 14.5% in
      the BMS and 7.8% in the SES groups (P = 0.0039), reflecting a reduction of
      reintervention rates (10.2% vs. 3.2%). A three-year follow-up was performed to
      extend previous short- to mid-term findings. METHODS AND RESULTS: Complete data
      at 3 years was available for 736 patients (99%). All-cause mortality was 6.7% in
      the tirofiban and 7.8% in the abciximab (P = 0.56) and 7.5% in the BMS vs 7.0 in
      the SES groups, P = 0.79. The composite of all-cause death or MI was identical at
      12.9% in tirofiban and abciximab groups, P = 0.99 and it occurred in 13.2% in the
      BMS vs. 12.6% in the SES groups (P = 0.83). The need for reintervention remained
      more than twice as common with BMS (13.7%; versus 6.2%, P = 0.0006). The
      cumulative rate of stent thrombosis (ST) did not differ. This is inspite of a
      higher very late definite, probable or possible ST thrombosis rate in the SES
      group. CONCLUSIONS: The 3-year follow-up of MULTISTRATEGY demonstrated comparable
      outcomes with HDB Tirofiban or abciximab and a sustained efficacy of SES to
      reduce reintervention with no difference in death, repeat MI or ST.

PMID- 21864918
TI  - Ganoderma lucidum ameliorate mitochondrial damage in isoproterenol-induced
      myocardial infarction in rats by enhancing the activities of TCA cycle enzymes
      and respiratory chain complexes.
AB  - BACKGROUND: Decreased mitochondrial function has been suggested to be one of the
      important pathological events in isoproterenol (ISO)-induced cardiotoxicity. In
      this communication, we have evaluated the protective effect of Ganoderma lucidum
      against ISO induced cardiac toxicity and mitochondrial dysfunction. METHODS:
      Cardiac toxicity was assessed by determining the activities of creatine kinase
      (CK) and lactate dehydrogenases (LDH) after subcutaneous injection of ISO (85
      mg/kg) at an interval of 24h for 2 days. The animals were sacrificed 24h after
      last ISO administration. G. lucidum (100 and 250 mg/kg, p.o.) was given to the
      rats once daily for 15 days prior to the ISO challenge. Similarly, alpha
      Tocopherol (100mg/kg, p.o) was kept as the standard. To assess the extent of
      cardiac mitochondrial damage, the activities of Krebs cycle dehydrogenases and
      mitochondrial complexes I, II, III, and IV as well as the level of ROS and
      mitochondrial membrane potential (DeltaPsimt) were evaluated. RESULTS:
      Administration of G. lucidum and alpha-tocopherol significantly protected the
      elevated activities of CK and LDH. Further, the activities of mitochondrial
      enzymes and the level of DeltaPsimt were significantly enhanced and the level of
      ROS was significantly declined in the G. lucidum and alpha-tocopherol treatments.
      CONCLUSION: The present study concluded that the cardiac mitochondrial enzymes
      are markedly declined by the ISO challenge and the administration G. lucidum and
      alpha-Tocopherol significantly protected mitochondria by preventing the decline
      of antioxidant status and DeltaPsimt or by directly scavenging the free radicals.

PMID- 21864919
TI  - Echocardiographic evaluation of left ventricular outflow tract hemodynamics in
      healthy children with anomalous left ventricular band.

PMID- 21864920
TI  - Catheter ablation of atrial fibrillation in Chinese elderly patients.

PMID- 21864921
TI  - The effect of delineation method and observer variability on bladder dose-volume
      histograms for prostate intensity modulated radiotherapy.
AB  - PURPOSE: To quantify the effect of delineation method on bladder DVH, observer
      variability (OV) and contouring time for prostate IMRT plans. MATERIALS AND
      METHODS: Planning CT scans and IMRT plans of 30 prostate cancer patients were
      anonymized. For 20 patients, 1 observer delineated the bladder using 9 methods.
      The effect of delineation method on the DVH curve, discrete dose levels and
      delineation time was quantified. For the 10 remaining CTs, 6 observers delineated
      bladder wall using 4 methods. Observer-based volume variation and intraclass
      correlation coefficient (ICC) were used to describe the dosimetric effects of OV.
      RESULTS: Manual delineation of the bladder wall (BW_m) was significantly slower
      than any other method (mean: 20 min vs. <= 13 min) and the dosimetric effect of
      OV was significantly larger (V70 Gy ICC: 0.78 vs. 0.98). Only volumes created
      using a 2.5mm contraction from the outer surface, and a method providing a
      consistent wall volume, showed no notable dosimetric differences from BW_m in
      both absolute and relative volume. CONCLUSIONS: Automatic contractions from the
      outer surface provide quicker, more reproducible and reasonably accurate
      substitutes for BW_m. The widespread use of automatic contractions to create a
      bladder wall volume would assist in the consistent application of IMRT dose
      constraints and the interpretation of reported dose.

PMID- 21864922
TI  - Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results.
AB  - PURPOSE: To determine local control, late toxicity and metastatic free survival
      (MFS) of patients treated with fractionated stereotactic radiation therapy (fSRT)
      for uveal melanoma (UM). METHODS AND MATERIALS: Between 1999 and 2007, 102 UM
      patients were included in a prospective study of a single institution (median
      follow-up (FU) 32 months; median tumor thickness 6 mm); five fractions of 10 Gy
      were given. Primary endpoints were local tumor control and late toxicity
      (including visual outcome and eye preservation). Secondary endpoint was MFS.
      RESULTS: Local tumor control was achieved in 96% of the patients. Fifteen
      enucleations were performed, 2-85 months after radiation. Four eyes were
      enucleated because of local tumor progression. Nine patients developed grade 3 or
      4 neovascular glaucoma (NVG), 19 developed severe retinopathy, 13 developed
      opticoneuropathy grade 3 or 4, 10 developed cataract grade 3, and 10 patients
      suffered from keratitis sicca. Best corrected visual acuity (BCVA) decreased from
      a mean of 0.26 at diagnosis to 0.16, 3 months after radiation and it gradually
      declined to 0.03, 4 years after therapy. The 5-year actuarial MFS was 75% (95%
      CIs: 62-84%). CONCLUSIONS: fSRT is an effective treatment modality for uveal
      melanoma with a good local control. With that, fSRT is a serious eye sparing
      treatment modality. However, our FU is relatively short. Also, the number of
      secondary enucleations is substantial, mainly caused by NVG.

PMID- 21864923
TI  - Helical tomotherapy for resected malignant pleural mesothelioma: dosimetric
      evaluation and toxicity.
AB  - This study evaluated adjuvant helical tomotherapy after extrapleural
      pneumonectomy +/- neo-adjuvant chemotherapy in 24 patients with malignant pleural
      mesothelioma. Toxicity was judged acceptable despite 2 cases (8%) of suspected
      grade 5 pneumonitis. With a mean follow-up of 7 months, 5 patients had distant
      and 2 local and distant failure.

PMID- 21864924
TI  - Anatomical and clinical predictors of acute bowel toxicity in whole pelvis
      irradiation for prostate cancer with Tomotherapy.
AB  - PURPOSE: Assessing predictors of acute bowel toxicity after whole-pelvis
      irradiation (WPRT) Image-guided Tomotherapy with simultaneous integrated boost on
      prostate/prostate bed. METHODS AND MATERIALS: In the period March 2005-April
      2009, 178 patients were treated with radical or adjuvant/salvage intent with WPRT
      Tomotherapy. Median dose to the pelvic nodes was 51.8 Gy/28 fractions while
      concomitantly delivering 65.5-74.2 Gy to prostate/prostatic bed. The impact of
      many anatomical and clinical parameters on >= Grade 2 acute bowel toxicity was
      investigated by logistic analyses. RESULTS: Only 15/178 patients (8.4%)
      experienced Grade 2 toxicity (none Grade 3). Main predictors at univariate
      analysis were nodal CTV (CTVN >= 380 cc; OR: 3.7, p=0.017), treatment duration (<
      40 days; OR: 6.2, p=0.006) and Grade 2 acute rectal toxicity (OR: 6.5, p=0.015).
      A multivariate analysis including only pre-treatment variables revealed an
      independent role of CTVN and age; if including treatment-related factors the best
      predictors were age, treatment duration and Grade 2 rectal toxicity. This last
      was correlated with the overlap between PTVN and loops (OVPN >= 51 cc; OR: 14.4,
      p=0.0003) that is representative of the volume of loops receiving the prescribed
      dose (51.8 Gy, 1.85 Gy/fr). CONCLUSIONS: Acute bowel toxicity after WPRT
      Tomotherapy is mild, relatively rare and associated to larger CTVN and older age.
      While efforts to further reduce it do not appear to be relevant, the pre
      treatment assessment of "high-risk" patients may help physicians in better
      managing symptoms. A prospective validation would be very important in confirming
      these results and in better refining dose-volume bowel effects including symptoms
      milder that the ones here investigated and retrospectively assessed.

PMID- 21864925
TI  - Treating intermediate-risk prostate cancer with hypofractionated external beam
      radiotherapy alone.
AB  - PURPOSE: Intermediate-risk prostate cancer has been treated in many ways; the
      most effective treatment is uncertain. Hypofractionated external beam
      radiotherapy (HyRT) is a short and convenient alternative treatment. We report
      our results of HyRT in intermediate-risk patients. MATERIAL AND METHODS: Eighty
      two patients with intermediate-risk prostate cancer were treated with 3
      dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at
      the isocenter without hormones. Intermediate-risk was defined as clinical stage
      T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7.
      The planning target volume consisted of the prostate plus a uniform 7 mm margin.
      Toxicity was prospectively graded by the Common Terminology Criteria version3.
      Biochemical relapse was defined as post-radiotherapy nadir PSA+2 ng/mL. RESULTS:
      With a median follow-up of 51 months, 5-year actuarial biochemical recurrence
      free survival is 95.4%. At the last follow-up visit, grade >= 2 late gastro
      intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No
      patient ever developed grade 4 or 5 toxicity. CONCLUSION: HyRT to a dose of 66 Gy
      in 22 fractions as a single treatment modality is convenient for patients and for
      the health care system and appears to provide similar results to other treatment
      choices.

PMID- 21864926
TI  - TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown results in
      radiosensitization of glioma cells.
AB  - BACKGROUND AND PURPOSE: The TP53 induced glycolysis and apoptosis regulator
      (TIGAR) functions to lower fructose-2,6-bisphosphate (Fru-2,6-P(2)) levels in
      cells, consequently decreasing glycolysis and leading to the scavenging of
      reactive oxygen species (ROS), which correlate with a higher resistance to cell
      death. The decrease in intracellular ROS levels in response to TIGAR may also
      play a role in the ability of p53 to protect from the accumulation of genomic
      lesions. Given these good prospects of TIGAR for metabolic regulation and p53
      response modulation, we analyzed the effects of TIGAR knockdown in U87MG and T98G
      glioblastoma-derived cell lines. METHODS/RESULTS: After TIGAR-knockdown in
      glioblastoma cell lines, different metabolic parameters were assayed, showing an
      increase in Fru-2,6-P(2), lactate and ROS levels, with a concomitant decrease in
      reduced glutathione (GSH) levels. In addition, cell growth was inhibited without
      evidence of apoptotic or autophagic cell death. In contrast, a clear senescent
      phenotype was observed. We also found that TIGAR protein levels were increased
      shortly after irradiation. In addition, avoiding radiotherapy-triggered TIGAR
      induction by gene silencing resulted in the loss of capacity of glioblastoma
      cells to form colonies in culture and the delay of DNA repair mechanisms, based
      in gamma-H2AX foci, leading cells to undergo morphological changes compatible
      with a senescent phenotype. Thus, the results obtained raised the possibility to
      consider TIGAR as a therapeutic target to increase radiotherapy effects.
      CONCLUSION: TIGAR abrogation provides a novel adjunctive therapeutic strategy
      against glial tumors by increasing radiation-induced cell impairment, thus
      allowing the use of lower radiotherapeutic doses.

PMID- 21864927
TI  - A quantitative microbial risk assessment for meatborne Toxoplasma gondii
      infection in The Netherlands.
AB  - Toxoplasma gondii is an important foodborne pathogen, and the cause of a high
      disease burden due to congenital toxoplasmosis in The Netherlands. The aim of
      this study was to quantify the relative contribution of sheep, beef and pork
      products to human T. gondii infections by Quantitative Microbial Risk Assessment
      (QMRA). Bradyzoite concentration and portion size data were used to estimate the
      bradyzoite number in infected unprocessed portions for human consumption. The
      reduction factors for salting, freezing and heating as estimated based on
      published experiments in mice, were subsequently used to estimate the bradyzoite
      number in processed portions. A dose-response relation for T. gondii infection in
      mice was used to estimate the human probability of infection due to consumption
      of these originally infected processed portions. By multiplying these
      probabilities with the prevalence of T. gondii per livestock species and the
      number of portions consumed per year, the number of infections per year was
      calculated for the susceptible Dutch population and the subpopulation of
      susceptible pregnant women. QMRA results predict high numbers of infections per
      year with beef as the most important source. Although many uncertainties were
      present in the data and the number of congenital infections predicted by the
      model was almost twenty times higher than the number estimated based on the
      incidence in newborns, the usefulness of the advice to thoroughly heat meat is
      confirmed by our results. Forty percent of all predicted infections is due to the
      consumption of unheated meat products, and sensitivity analysis indicates that
      heating temperature has the strongest influence on the predicted number of
      infections. The results also demonstrate that, even with a low prevalence of
      infection in cattle, consumption of beef remains an important source of
      infection. Developing this QMRA model has helped identify important gaps of
      knowledge and resulted in the following recommendations for future research:
      collect processing-effect data in line with consumer style processing and acquire
      product specific heating temperatures, investigate the presence and concentration
      of viable bradyzoites in cattle, determine the effect of mincing meat on
      bradyzoite concentrations using actual batch sizes, and obtain an estimate of the
      fraction of meat that has been frozen prior to purchase. With more accurate data
      this QMRA model will aid science-based decision-making on intervention strategies
      to reduce the disease burden from meatborne T. gondii infections in The
      Netherlands.

PMID- 21864929
TI  - Subtyping of Listeria monocytogenes at the haplotype level by Fourier transform
      infrared (FT-IR) spectroscopy and multivariate statistical analysis.
AB  - Listeria monocytogenes is a widespread foodborne pathogen that represents a major
      concern with respect to food safety. Rapid identification of this bacterium at a
      subspecies level is important to trace back an outbreak and improve risk-based
      inspection programs. A method for subtyping L. monocytogenes at the serotype and
      haplotype levels was developed using Fourier transform infrared (FT-IR)
      reflectance microscopy. Thirty strains of L. monocytogenes belonging to four
      different PCR serotypes (1/2a, 1/2b, 4b, and 4c) that had previously been
      characterized by Multilocus genotyping (MLGT) and Pulsed field gel
      electrophoresis (PFGE) assays were used in this study. The FT-IR based
      identification and classification was compared to the known MLGT and PFGE
      subtyping of the L. monocytogenes. Canonical variate analysis (CVA) of the
      spectra resulted in 96.6% correct identification of L. monocytogenes at the
      serotype level. Hierarchical cluster analysis (HCA) and CVA of the spectra showed
      91.7% correct identification of strains at the haplotype level consistent with
      their MLGT groupings. FT-IR spectra of strains were also differentiated correctly
      in accordance with their PFGE haplotyping. Additionally, by using HCA of FT-IR
      spectra, each bacterium was differentiated at the strain level. Starting from a
      pure culture, this method enabled classification of L. monocytogenes at the
      serotype, haplotype, and/or strain level within 18 h, which is faster and
      potentially less expensive than the molecular methods and previous FT-IR methods.
      This is the first report of the identification of L. monocytogenes at the
      haplotype level using FT-IR.

PMID- 21864928
TI  - Evaluation of DNA extraction methods for Bacillus anthracis spores spiked to food
      and feed matrices at biosafety level 3 conditions.
AB  - The DNA extraction efficiency from milk, whey, soy, corn gluten meal, wheat
      powders and heat-treated corn grain that were spiked with Bacillus anthracis and
      Bacillus thuringiensis spores was determined. Two steps were critical: lysis of
      the spores and binding of the free DNA to the DNA binding magnetic beads in the
      presence of the interfering powders. For the guanidine-thiocyanate based
      Nuclisens lysis buffer from Biomerieux we found that between 15 and 30% of the
      spores survived the lysis step. As most lysis buffers in DNA/RNA extraction kits
      are guanidine based it is likely that other lysis buffers will show a similar
      partial lysis of the Bacillus spores. Our results show that soybean flour and
      wheat flour inhibited the DNA extraction process strongest, leading to unreliable
      DNA extractions when using too much of the matrix. For corn gluten meal, heat
      treated corn grain and milk powders, DNA extraction efficiencies in the presence
      of 100mg and 10mg of powder resulted in 70%-95% reduced DNA recoveries. The
      inhibition was, however, reliable and intermediate compared to the inhibition by
      soy and wheat. Whey powder had the lowest inhibitory effect on DNA-extraction
      efficiency and recoveries of 70-100% could be reached when using 10mg of powder.
      The results show that reducing the amount of matrix leads to better DNA
      extraction efficiencies, particularly for strongly inhibiting powders such as soy
      and wheat. Based on these results, a standard protocol to directly isolate DNA
      from micro-organisms present in complex matrixes such as food and feed powders
      was designed.

PMID- 21864930
TI  - From farm to fork follow-up of thermotolerant campylobacters throughout the
      broiler production chain and in human cases in a Hungarian county during a ten
      months period.
AB  - A study tracking thermotolerant campylobacters from the setting of the broilers
      throughout the whole rearing period, slaughter and sale of chicken products in
      five consecutive broiler rotations of the same henhouse as well as in two
      different other farms was conducted in a well-defined geographic area (Hajdu
      Bihar county, Hungary) between March 2006 and Feb 2007. All notified cases of
      human campylobacteriosis in this area during the study period were also included.
      One hundred and one, 44, 23 and 282 Campylobacter jejuni and 13, 15, 20 and 60C.
      coli were isolated from broiler houses, slaughterhouses, retail shops and human
      samples, respectively. Sixty-two isolates collected from broilers or their
      environment selected from different flocks (57C. jejuni, 5C. coli), 92 isolates
      collected from abattoirs and retail shops (72C. jejuni, 20C. coli), as well as 85
      randomly selected human isolates (74C. jejuni, 11C. coli) were subjected to PFGE
      analysis using restriction enzymes KpnI and SmaI. Sixty-six of the isolates
      produced unique Sma-Kpn profiles; the majority (46) of these were of human
      origin. The remaining isolates formed PFGE clusters of between 2-25 isolates with
      14 (12C. jejuni and 2C. coli) main clusters comprised of five or more isolates
      with identical KpnI-SmaI patterns. Two genetic clones of C. jejuni (clone A,
      n=25; clone B, n=20) included 18% of isolates from different sources. Generally,
      isolates from one cluster were found in 1-3 different flocks, notably, clone B
      was present in three rotations including those from the two independent farms.
      Six of the seven investigated flocks had one or two characteristic prevalent
      clones. Transmission of clones between consecutive flocks was frequently seen.
      Spread of both C. jejuni and C. coli was traced multiple times along the food
      chain; eight C. jejuni, but no C. coli clones were detected both in broilers and
      humans. These data suggest that broilers were the major source for C. jejuni but
      not for C. coli in the studied area and period. For C. jejuni the carryover of
      strains between consecutive flocks may be a common event, but the strain is
      eventually replaced by another and consecutive carryover events seem to be
      infrequent. The majority of the human disease was due to nonepidemic strains;
      some clones were transmitted from more than one broiler flocks (including
      epidemiologically unrelated flocks) to humans multiple times.

PMID- 21864931
TI  - Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune
      diabetes in adults.
AB  - Aberrant DNA methylation in T cells has been linked to pathogenesis of autoimmune
      diseases. To investigate genomic and gene-specific DNA methylation levels in
      CD4(+) T cells from patients with latent autoimmune diabetes in adults (LADA),
      and to investigate changes in the expression of genes that regulate methylation
      as well as the autoimmune-related gene FOXP3 in these patients. Global CD4(+) T
      cell DNA methylation was measured in 15 LADA patients and 11 healthy controls
      using a methylation quantification kit. mRNA levels of DNA methytransferases
      (DNMTs), methyl-DNA binding domain proteins (MBDs) and FOXP3 were measured by
      real time PCR. Methylation of a FOXP3 regulatory element region was determined by
      bisulphite genomic sequencing. Genomic DNA methylation in CD4(+) T cells from
      LADA patients was significantly increased compared to controls. DNMT3b mRNA
      levels were higher in CD4(+) T cells from LADA patients than in controls. DNMT3b
      expression positively correlated with global DNA methylation in LADA CD4(+) T
      cells. FOXP3 expression was decreased, and the FOXP3 promoter region was
      hypermethylated in CD4(+) T cells from LADA patients compared with controls. DNA
      methylation levels are altered in CD4(+) T cells from LADA patients, which may
      contribute to disease onset and progression by affecting the expression of
      autoimmune-related genes.

PMID- 21864932
TI  - Differential association of retinal arteriolar and venular caliber with diabetes
      and retinopathy.
AB  - AIMS: To describe the relationship of retinal arteriolar and venular caliber with
      diabetes, retinopathy and hyperglycemia, in an Asian Indian population. METHODS:
      This was a population-based cross-sectional study of 3400 (75.6% response rate)
      Singapore ethnic Indians aged 40-80 years. Central retinal arteriolar equivalent
      (CRAE) and central retinal venular equivalent (CRVE) were obtained using a
      validated computer-assisted program. Diabetes mellitus was identified using
      standardized criteria. Diabetic retinopathy was graded based on the modified
      Airlie House Classification System. RESULTS: There were 980 (32.2%) participants
      with diabetes. Of these, 327 (33.4%) had diabetic retinopathy. After multivariate
      adjustment, diabetic persons had a wider CRAE (145.23MUm vs 142.38MUm, P<0.001).
      This relationship was stronger in persons without hyperlipidemia (P
      interaction<0.1). Among diabetic participants, wider CRVE was related to
      increasing severity of retinopathy (P for trend<0.05) and this association may be
      altered by hypertensive status. Retinal arteriolar caliber widened with
      increasing glucose (P<0.001) and HbA1C (P<0.001) levels. CONCLUSIONS: In Indian
      adults, wider retinal arteriolar caliber is associated with diabetes and
      hyperglycemia, while wider retinal venular caliber is associated with diabetic
      retinopathy. This is consistent with white populations and confirms the
      differential systemic association of retinal vascular caliber in Asian Indians.

PMID- 21864933
TI  - Confirmation of the role of diabetes in the local recurrence of surgically
      resected non-small cell lung cancer.
AB  - PURPOSE: We recently demonstrated that diabetes mellitus was an independent risk
      factor for local recurrence (LR) for patients undergoing resection of non-small
      cell lung cancer (NSCLC). This investigation was performed to confirm or refute
      this finding in a different patient cohort. MATERIALS AND METHODS: Patients were
      eligible if they did not have a second primary cancer within 5 years of the
      original diagnosis, had at least 3-month follow-up, and did not receive
      radiotherapy. There were 373 and 168 patients in the original (P1) and
      confirmatory (P2) cohorts, respectively, with 66 and 30 patients with diabetes.
      RESULTS: The median follow-up was 33 months (range, 3-98 months). Diabetes was an
      independent risk factor for LR in a Cox model in both the P2 (p=0.05, hazard
      ratio [HR] 2.15) and P1 (p=0.008, HR 1.90) cohorts, separately from BMI, glucose
      control, and the presence of the metabolic syndrome. The rates of LR in the
      patients with diabetes after combining the cohorts at 2, 3, and 5 years were 23%,
      33%, and 56%, respectively; these rates were 15%, 19%, and 26% in non-diabetics.
      In multivariate Cox regression and competing risk analysis of the combined
      cohorts, the HRs for LR in patients with diabetes exceeded those of more
      established risk factors for LR including a 1-cm increase in tumor size and
      lymphovascular invasion. CONCLUSIONS: Diabetes was confirmed to be an independent
      predictor of the risk of LR following resection of NSCLC.

PMID- 21864934
TI  - Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer
      solitary metastases: systematic review and analysis of reported cases.
AB  - BACKGROUND: Although patients with stage IV non-small cell lung cancer (NSCLC)
      have a poor prognosis, a subset of patients with solitary brain or adrenal
      metastasis have more favorable outcome following surgical resection.
      Nevertheless, the outcome and predictive factors for survival following
      metastatectomy for patients with other metastatic sites are not well defined.
      METHODS: We performed a systematic review using PUBMED database for all articles
      which included patients with NSCLC and solitary metastasis to sites other than
      the adrenal gland or the brain who had undergone resection of their metastasis
      and definitive treatment of the primary lung cancer. Potential prognostic factors
      on survival including age, sex, histology, T and N stage of the primary tumor,
      synchronous vs. metachronous presentation, visceral vs. non-visceral metastasis
      and the use of perioperative chemotherapy were analyzed using multi-variable Cox
      proportional hazard model. RESULTS: 62 cases were eligible for the analysis. The
      5-year survival rate was 50% for the entire cohort. Mediastinal lymph node
      involvement was independently predictive of inferior outcome; 5-year survival
      rate 0% vs. 64% in favor of no involvement, p<0.001. Similarly, patients with
      intra-thoracic stage III disease had an inferior outcome compared to patients
      with stage II and stage I disease: 5-year survival rate 0% vs. 77% and 63%,
      respectively, p<0.001. Other factors have no effect on outcome. CONCLUSION:
      Selected patients with distant metastatic NSCLC can achieve long term survival
      following metastatectomy and definitive treatment of the primary tumor.
      Mediastinal lymph node involvement is associated with poor prognosis.

PMID- 21864935
TI  - Melanocyte-keratinocyte transplantation procedure in the treatment of vitiligo:
      the experience of an academic medical center in the United States.
AB  - BACKGROUND: Vitiligo is a disfiguring disease with limited treatment options.
      Surgical treatment is underused in the United States because of perceived risk of
      infection, costs, and difficulty of the procedure. OBJECTIVE: We sought to
      determine the efficacy and safety of the melanocyte-keratinocyte transplantation
      procedure (MKTP) in an academic dermatology department in the United States.
      METHODS: This prospective, uncontrolled, open-label study enrolled patients aged
      18 years or older with a self-reported history of vitiligo and no new or
      expanding lesions for at least 6 months before surgery. Patients with a history
      of koebnerization or keloid formation were excluded. Patients underwent
      autologous MKTP. Repigmentation during a 3- to 6-month follow-up period was
      assessed categorically and by modified Vitiligo Area Scoring Index. Safety was
      assessed by frequency of adverse events. RESULTS: Of the 28 patients who
      underwent 36 procedures, 23 patients who underwent 29 procedures completed the 3-
      to 6-month follow-up period. Data for these 29 procedures show excellent
      repigmentation (ie, 95%-100%) after the MKTP in 17%, and good repigmentation (ie,
      65%-94%) in 31%. Fair (64%-25%) and poor (24%-0%) repigmentation were achieved in
      10% and 41% of patients, respectively. Average percent change in Vitiligo Area
      Scoring Index was -45% (95% confidence interval -64% to -26%), signifying an
      improvement in pigmentation. LIMITATIONS: Limitations include small sample size
      and lack of a control group. CONCLUSIONS: The MKTP is an effective and well
      tolerated procedure based upon categorical and Vitiligo Area Scoring Index
      assessments of repigmentation.

PMID- 21864936
TI  - Escherichia coli bacteraemia: how preventable is it?
AB  - Mandatory bacteraemia reporting was extended to include Escherichia coli from
      June 2011. The purpose of this study was to investigate whether the success seen
      in reducing meticillin-resistant Staphylococcus aureus infection rates could be
      duplicated with E. coli. All cases of E. coli bacteraemia occurring at our Trust
      in 2010 were reviewed. There were 216 episodes of E. coli bacteraemia, of which
      63% were community-acquired. Only 19% had a potentially preventable cause
      identified, the majority (71%) of whom had urinary catheter-associated
      bacteraemia. These data must be kept in mind should targets to reduce E. coli
      bacteraemia be set in the future.

PMID- 21864937
TI  - Risk factors for bacteraemia attributable to Pseudomonas aeruginosa resistant to
      imipenem, levofloxacin, or gentamicin.
AB  - We studied the risk factors associated with resistance to imipenem, levofloxacin
      and gentamicin in Pseudomonas aeruginosa isolated from blood cultures of 175
      patients in a hospital in Japan. Imipenem resistance was associated with transfer
      from another hospital, and receiving antifungal medication. Gentamicin resistance
      was associated with previous administration of a penicillin. No specific risk
      factors were associated with levofloxacin resistance.

PMID- 21864938
TI  - Control of an outbreak of diarrhoea in a vascular surgery unit caused by a high
      level clindamycin-resistant Clostridium difficile PCR ribotype 106.
AB  - This report describes an outbreak of Clostridium difficile infection (CDI) in a
      vascular surgery ward in 2009 caused by a high-level clindamycin-resistant
      ribotype 106. A case of CDI was defined as a patient with diarrhoea, positive for
      C. difficile toxin and negative for other enteric pathogens. Cultures were sent
      to the Scottish Salmonella Shigella and Clostridium difficile Reference
      Laboratory (SSSCDRL) for PCR ribotyping, antibiotic susceptibility testing and
      PCR detection of ermB. The mean age of the nine patients was 73 years (range: 38
      90 years). All had received clindamycin and ciprofloxacin. All cases were typed
      as PCR ribotype 106 and they showed high-level resistance to clindamycin. Five of
      these isolates were tested by PCR for the presence of the ermB gene and no
      amplification was detected. This strain has rarely been isolated from patients on
      this ward. The outbreak was controlled successfully by closure of the ward with
      terminal cleaning, reinforcement of infection control precautions and the
      introduction of a new antibiotic policy. It is notable that this outbreak was
      caused by a strain with high-level clindamycin resistance not mediated by ermB.
      It also re-emphasizes that outbreaks of CDI can be caused by C. difficile PCR
      ribotypes other than 027. The outbreak was most likely associated with the use of
      clindamycin and ciprofloxacin cross-infection with spores in this environment.
      Implementation of strict infection control precautions, antimicrobial stewardship
      and enhanced environmental cleaning are key components in managing such an
      outbreak successfully. The number of meticillin-resistant Staphylococcus aureus
      acquisitions also fell substantially after these interventions.

PMID- 21864939
TI  - Impact of medications on bacterial growth in syringes.
AB  - Syringes used to administer intravenous medications in an intensive care unit
      were cultured, and the isolates were compared with those from positive blood
      cultures from the same patients. The overall contamination rate was 16%, and
      syringes used for drugs such as insulin, which support bacterial growth, had
      higher contamination rates. All syringes should be changed routinely after 6h.

PMID- 21864940
TI  - Correlation between glove use practices and compliance with hand hygiene in a
      multicenter study with elderly patients.
AB  - In a study conducted in 11 health care settings for elderly patients, we
      demonstrated a significant negative correlation between the proportion of glove
      use outside any risk of exposure to body fluids and compliance with hand hygiene
      (P < .02). This result underscores a major limitation of strategies for
      controlling the spread of multidrug-resistant bacteria that recommend systematic
      glove use for each contact with carriers or their environment.

PMID- 21864941
TI  - Do hospital visitors wash their hands? Assessing the use of alcohol-based hand
      sanitizer in a hospital lobby.
AB  - BACKGROUND: Reports regarding hand hygiene compliance (HHC) among hospital
      visitors are limited. Although there is an implicit assumption that the
      availability of alcohol-based hand sanitizer (AHS) promotes visitor HHC, the
      degree of AHS use by visitors remains unclear. To assess AHS use, we observed
      visitor HHC and how it is affected by visual cues in a private university
      hospital. METHODS: Using an observational controlled study, we tested 3
      interventions: a desk sign mandating all visitors to use AHS, a free-standing AHS
      dispenser directly in front of a security desk, and a combination of a
      freestanding AHS dispenser and a sign. RESULTS: HHC was 0.52% at baseline and did
      not improve significantly when the desk sign was provided as a cue 0.67% (P =
      .753). However, HHC did improve significantly with use of the freestanding AHS
      dispenser (9.33%) and the sign and dispenser combination (11.67%) (P < .001 for
      all comparisons of dispenser alone and sign and dispenser with baseline and sign
      alone). The degree of improvement with the sign and dispenser combination over
      the dispenser was not statistically significant. CONCLUSIONS: Hospital visitors
      represent an important factor in infection prevention. A coordinated effort is
      needed to increase visitor HHC, including an evaluation of the AHS placement,
      education of visitors on the importance of HHC, and evaluation of corresponding
      changes in hand hygiene behavior.

PMID- 21864942
TI  - An effective intervention to limit the spread of an epidemic carbapenem-resistant
      Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
AB  - BACKGROUND: The highly transmissible and virulent carbapenem-resistant Klebsiella
      pneumoniae (CRKP) KPC-3 strain has been spreading in our medical center and in
      other centers in Israel since 2006. An intervention that aimed to diminish its
      prevalence was constructed and applied in our institute. METHODS: We analyzed the
      efficacy of the intervention during the years 2006-2010 using quasi-experimental
      methodology. The intervention included guidelines for patient isolation,
      cohorting, and environment cleaning; education of staff; and a computerized
      notification system that flags CRKP carriers and provides instructions. The
      efficacy of the program was evaluated through 3 quantifiable parameters:
      incidence of CRKP isolates from clinical samples, rate of cross-infections, and
      rate of screening for CRKP carriage in patients at risk identified by rectal
      samples. RESULTS: The incidence of CRKP decreased by 16-fold (P < .001), and this
      decrease was sustained for 30 months. The rate of cross-infection decreased from
      6% during 2007-2008 to 2.7% in 2009-2010 (P < .05). This period saw an increased
      rate of active surveillance for carriers, from 20% to 89%. CONCLUSIONS: A
      comprehensive infection control program can contain an outbreak of the CRKP KPC-3
      strain in acute care hospitals during a nationwide outbreak of this strain.

PMID- 21864943
TI  - Prevalence and risk factors for methicillin-resistant Staphylococcus aureus
      colonization in a diabetic outpatient population: a prospective cohort study.
AB  - BACKGROUND: Diabetes mellitus is a risk factor for methicillin-resistant
      Staphylococcus aureus (MRSA) colonization and infection. We attempted to
      determine the prevalence and risk factors for MRSA colonization in a population
      of outpatients with diabetes. METHODS: This prospective cohort study enrolled
      patients with diabetes. Anterior nares cultures were obtained from patients with
      diabetes admitted to outpatient endocrinology and metabolism clinics, and risk
      factors for MRSA colonization were analyzed. RESULTS: Out of the 304 patients
      evaluated, 127 (41.9%) were colonized with S aureus and 30 (9.9%) were colonized
      with MRSA. Overall, 23.6% of all S aureus isolates were MRSA. In multivariate
      analysis, factors independently associated with an increased risk of MRSA
      colonization included the presence of connective tissue disease (odds ratio,
      7.075; 95% confidence interval, 2.157-23.209; P = .001) and insulin therapy (odds
      ratio, 3.910; 95% confidence interval, 1.652-9.251; P = .002). CONCLUSIONS: The
      prevalence of MRSA colonization in our sample of diabetic outpatients was 9.9%.
      Independent risk factors for MRSA colonization were the presence of connective
      tissue disease and insulin use. A better understanding of the epidemiology and
      risk factors for nasal MRSA colonization in the persons with diabetes may have
      significant implications for the treatment and prevention of MRSA infections.

PMID- 21864944
TI  - The associations between organizational culture and knowledge, attitudes, and
      practices in a multicenter Veterans Affairs quality improvement initiative to
      prevent methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Previous research demonstrates that organizational culture (OC) and
      knowledge, attitudes, and practices of health care personnel are associated with
      the overall success of infection control programs; however, little attention has
      been given to the relationships among these factors in contributing to the
      success of quality improvement programs. METHODS: Cross-sectional surveys
      assessing OC and knowledge, attitudes, and practices related to methicillin
      resistant Staphylococcus aureus (MRSA) were distributed to 16 medical centers
      participating in a Veterans Affairs MRSA prevention initiative in 2 time periods.
      Factor analysis was performed on the OC survey responses, and factor scores were
      generated. To assess associations between OC and knowledge, attitudes, and
      practices of health care personnel, regression analyses were performed overall
      and then stratified by job type. RESULTS: The final analyzable sample included
      2,314 surveys (43% completed by nurses, 9% by physicians, and 48% by other health
      care personnel). Three OC factors emerged accounting for 53% of the total
      variance: "Staff Engagement," "Overwhelmed/Stress-Chaos," and "Hospital
      Leadership." Overall, higher Staff Engagement was associated with greater
      knowledge scores, better hand hygiene practices, fewer reported barriers, and
      more positive attitudes. Higher Hospital Leadership scores were associated with
      better hand hygiene practices, fewer reported barriers, and more positive
      attitudes. Conversely, higher Overwhelmed/Stress-Chaos scores were associated
      with poorer reported prevention practices, more barriers, and less positive
      attitudes. When these associations were stratified by job type, there were
      significant associations between OC factors and knowledge for nurses only,
      between OC factors and practice items for nurses and other health care personnel,
      and between OC factors and the barriers and attitudes items for all job types. OC
      factors were not associated with knowledge and practices among physicians.
      CONCLUSIONS: Three OC factors-Staff Engagement, Overwhelmed/Stress-Chaos, and
      Hospital Leadership-were found to be significantly associated with individual
      health care personnel knowledge, attitudes, and self-reported practices regarding
      MRSA prevention. When developing a prevention intervention program, health care
      organizations should not only focus on the link between OC and the knowledge,
      attitudes, and practices of health care personnel, but also target programs based
      on health care personnel type to maximize their effectiveness.

PMID- 21864945
TI  - Impact of multiple consecutive donnings on filtering facepiece respirator fit.
AB  - BACKGROUND: A concern with reuse of National Institute for Occupational Safety
      and Health-certified N95 filtering facepiece respirators (FFRs) is that multiple
      donnings could stress FFR components, impairing fit. This study investigated the
      impact of multiple donnings on the facepiece fit of 6 N95 FFR models using a
      group of 10 experienced test subjects per model. METHODS: The TSI PORTACOUNT Plus
      and N95 Companion accessory were used for all tests. After qualifying by passing
      a standard Occupational Safety and Health Administration fit test, subjects
      performed up to 20 consecutive tests on an individual FFR sample using a modified
      protocol. Regression analyses were performed for the percentage of donnings
      resulting in fit factors (FFs) >=100 for all 6 FFR models combined. RESULTS:
      Regression analyses showed statistical significance for donning groups 1-10, 1
      15, and 1-20. The mean percentage of donnings with an FF >=100 was 81%-93% for
      donning group 1-5, but dropped to 53%-75% for donning group 16-20. CONCLUSIONS:
      Our results show that multiple donnings had a model-dependent impact on fit for
      the 6 N95 models evaluated. The data suggest that 5 consecutive donnings can be
      performed before FFs consistently drop below 100.

PMID- 21864946
TI  - Occurrence of and risk factors for methicillin-resistant Staphylococcus aureus at
      a teaching hospital in Philadelphia.
AB  - Manual medical record mining and data analysis were performed at a tertiary care
      university teaching hospital to establish the rate of occurrence of and risk
      factors for infection with methicillin-resistant Staphylococcus aureus (MRSA).
      Patients with surgical site infections had the highest rate of MRSA infection,
      representing 59% of the MRSA infections recorded. The mortality rate in patients
      with relapsed MRSA was 45% (13 of 30), compared with no deaths in 149 new MRSA
      cases. The majority of deaths in patients with relapsed MRSA occurred in the
      intensive care unit.

PMID- 21864947
TI  - Development of a novel furocoumarin derivative inhibiting NF-kappaB dependent
      biological functions: design, synthesis and biological effects.
AB  - Nuclear Factor kappaB (NF-kappaB) plays a very important role in the control of
      gene expression and is deeply involved in several human pathologies. Accordingly,
      molecules targeting NF-kappaB dependent biological functions are considered of
      great interest. Virtual screening of furocoumarin libraries against NF-kappaB p50
      allowed to rank compounds in respect to their expected ability to bind NF-kappaB
      and the identified compound might be considered for the development of analogs to
      be tested for biological activity on inhibition of NF-kappaB/DNA complex
      formation. The data reported in the present paper suggest that, following this
      approach, the best ranked compounds identified by virtual screening (a) strongly
      bind in silico to NF-kappaB and (b) efficiently inhibit the molecular
      interactions between (32)P-labeled NF-kappaB double stranded DNA and p50 or
      p50/p65 complex. These data allowed to develop a novel lead of great interest for
      inhibiting NF-kappaB dependent biological functions. This novel molecule
      (compound 2), bearing a methyl group in the 9 position of the psoralen nucleus,
      exhibits high efficiency in inhibiting NF-kappaB/DNA interactions. In addition,
      we found that compound 2 is a potent inhibitor of IL-8 gene expression in TNF
      alpha treated IB3-1 cystic fibrosis cells. Taken together, our data indicate that
      compound 2 might find an important place in the set of molecules of interest for
      the development of pharmaceutical strategies against the inflammatory phenotype
      of cystic fibrosis.

PMID- 21864948
TI  - Dynamics of different arachidonic acid orientations bound to prostaglandin
      endoperoxide synthases.
AB  - Prostaglandin endoperoxide synthases (PGHSs) catalyze the conversion of
      arachidonic acid (AA) into prostaglandin endoperoxide H(2). This reaction
      requires a specific orientation of AA within the active site, but an alternative
      crystallographic binding orientation for AA also exists. Since the origin of this
      alternative complex, and its potential relevance, have been neglected so far, we
      have characterized the dynamics of both orientations of AA, bound to PGHS-1 and 
      2, in order to obtain new insights for designing PGHSs inhibitors. Our results
      indicate that AA in the alternative orientation seems to be less stable, moving
      toward Arg120. Such potentially minor orientation of AA can be related to
      crystallographic complexes of anti-inflammatory agents, pointing to an alternate
      SAR on PGHSs inhibitors.

PMID- 21864949
TI  - Synthesis and antioxidant activity of oxazolyl/thiazolylsulfonylmethyl pyrazoles
      and isoxazoles.
AB  - A new class of oxazolyl/thiazolylsulfonylmethyl pyrazoles (10-13) and isoxazoles
      (14, 15) were prepared from the synthetically vulnerable intermediate E
      styrylsulfonylacetic acid methyl ester (1) and studied their antioxidant
      activity.

PMID- 21864950
TI  - Conjugation of substituted ferrocenyl to thiadiazine as apoptosis-inducing agents
      targeting the Bax/Bcl-2 pathway.
AB  - Ferrocene compounds are a class of biologically active compounds that has
      antitumour and antifungal properties. This study investigated the induction of
      apoptosis in human fibrosarcoma cells (HT1080) after treatment with a series of 6
      ferrocenyl-3-subsituted7H-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazine (FTFs). We
      found that FTFs could suppress the viability of HT1080 cells. Cell cycle analysis
      showed that proliferative inhibition of HT1080 cells occurred through apoptosis,
      as the cells were blocked in G1 phase. Moreover, mitochondrial membrane staining
      assay demonstrated that FTFs exposure significantly decreased mitochondrial
      membrane potential. Finally, under the stress of FTFs, Bax/Bcl-2 ratio in HT1080
      cells was significantly increased. These results suggested that FTFs-induced
      apoptosis in HT1080 cells may work dependent on a Bax/Bcl-2 pathway.

PMID- 21864951
TI  - Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents.
AB  - A series of N2-{2-[4-aryl(benzyl)-1-piperazinyl(piperidinyl)]ethyl}pyrrolo[3,4
      d]pyridazinones 4 and related derivatives 5 were synthesized as potential
      analgesic agents. The structures of the new compounds were elucidated by micro,
      spectral and X-ray analysis. Analgesic activity of the compounds was investigated
      in the phenylbenzoquinone induced 'writhing' and 'hot plate' test in mice and at
      radioligand binding assay. At 'writhing' test all compounds, without exception,
      were more active than acetylsalicylic acid (ASA) with ED(50) values ranging from
      0.04 to 11 mg/kg (i.p.) (ED(50) for ASA--39.15 mg/kg). Analgesic effect at the
      'hot plate' test was observed for three compounds 4c,e,f at the dose 3-5 times
      higher then that of morphine (ED(50)-3.39 mg/kg). At radioligand binding assay of
      4c,e,f only compound 4f exhibited affinity for the MU-opioid receptors similar to
      that of Tramadol. The acute toxicity of the pyrrolopyridazinones 4, 5 were also
      studied and non toxic effect was observed at the 2000 mg/kg (5a 1420 mg/kg) i.p.
      dose level. On the basis of the available pharmacological data S-A relationship
      is discussed. The preferred conformational characteristic of 4, taken 4c as an
      example, was also described.

PMID- 21864952
TI  - Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP
      and DCK analogues.
AB  - In a continuing study of novel anti-HIV agents with drug-like structures and
      properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and
      DCK analogues (8-37) were designed and synthesized. All newly synthesized seco
      compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase
      (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK
      (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and
      32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to
      1.93 MUM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy
      2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly
      synthesized compounds with EC(50) values of 0.47 and 0.88 MUM, and TI of 96 and
      51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds
      exhibited better chemical stability in acidic conditions compared with DCP and
      DCK compounds. Overall, the results suggested that seco-DCP analogues with
      simplified structures may be more favorable for development as novel anti-HIV
      candidates.

PMID- 21864953
TI  - [Antiphospholipid antibodies and the risk of thrombosis: a comparative survey
      between chronic immune thrombocytopenia and primary antiphospholipid syndrome].
AB  - PURPOSE: The prevalence of antiphospholipid antibodies (APA) in patients with
      immune thrombocytopenic purpura (ITP) varies from 25 to 75% in the literature.
      The risk of thrombosis in this subgroup of patients is debated. In parallel,
      thrombocytopenia is present in 22 to 42% of patients with antiphospholipid
      syndrome (APS). PATIENTS AND METHODS: The main study objective was to compare the
      profile at diagnosis of lupus anticoagulant (LA), anticardiolipin antibody (ACL)
      and anti-beta(2)GP-I antibody between a cohort of 93 chronic ITP patients and a
      cohort of 27 primary APS patients. The secondary objectives were: to evaluate the
      risk of thrombosis in ITP patients depending on the presence of APA; to compare
      the profile of APA and to assess the occurrence of lupus in APS patients
      depending on the presence of thrombocytopenia. RESULTS: In ITP patients, the
      prevalence of APA was 25%; association of several different APA was less frequent
      than in APS patients; mean titles of ACL and anti-beta(2)GP-I antibodies were
      comparable between the two cohorts; two spontaneous venous thromboses occurred in
      ITP patients, with no particular profile of APA (median follow-up: 36 months).
      Thrombocytopenia was present in 26% of APS patients; it was always moderate and
      asymptomatic, and sometimes intermittent; no particular profile of APA was
      associated to thrombocytopenia; only one thrombocytopenic patient developed a
      systemic lupus and no particular profile of APA could be found associated (median
      follow-up: 48 months). CONCLUSION: ITP patients with APA have less frequently an
      association of different APA than APS patients do; their risk of thrombosis
      appears low.

PMID- 21864954
TI  - Plutonium bioaccumulation in seabirds.
AB  - The aim of the paper was plutonium (238Pu and 239+240Pu) determination in
      seabirds, permanently or temporarily living in northern Poland at the Baltic Sea
      coast. Together 11 marine birds species were examined: 3 species permanently
      residing in the southern Baltic, 4 species of wintering birds and 3 species of
      migrating birds. The obtained results indicated plutonium is non-uniformly
      distributed in organs and tissues of analyzed seabirds. The highest plutonium
      content was found in the digestion organs and feathers, the smallest in skin and
      muscles. The plutonium concentration was lower in analyzed species which feed on
      fish and much higher in herbivorous species. The main source of plutonium in
      analyzed marine birds was global atmospheric fallout.

PMID- 21864955
TI  - Recruitment of the plantar intrinsic foot muscles with increasing postural
      demand.
AB  - BACKGROUND: The aim of this study was to determine the difference in activation
      patterns of the plantar intrinsic foot muscles during two quiet standing tasks
      with increasing postural difficulty. We hypothesised that activation of these
      muscles would increase with increasing postural demand and be correlated with
      postural sway. METHODS: Intra-muscular electromyographic (EMG) activity was
      recorded from abductor hallucis, flexor digitorum brevis and quadratus plantae in
      10 healthy participants while performing two balance tasks of graded difficulty
      (double leg stance and single leg stance). These two standing postures were used
      to appraise any relationship between postural sway and intrinsic foot muscle
      activity. FINDINGS: Single leg stance compared to double leg stance resulted in
      greater mean centre of pressure speed (0.24 m s(-1) versus 0.06 m s(-1),
      respectively, P <= 0.05) and greater mean EMG amplitude for abductor hallucis (P
      >= 0.001, ES=0.83), flexor digitorum brevis (P <= 0.001, ES=0.79) and quadratus
      plantae (P <= 0.05, ES=0.4). EMG amplitude waveforms for all muscles were
      moderate to strongly correlated to centre of pressure (CoP) medio-lateral
      waveforms (all r >= 0.4), with muscle activity amplitude increasing with medial
      deviations of the CoP. Intra-muscular EMG waveforms were all strongly correlated
      with each other (all r >= 0.85). INTERPRETATIONS: Activation of the plantar
      intrinsic foot muscles increases with increasing postural demand. These muscles
      are clearly important in postural control and are recruited in a highly co
      ordinated manner to stabilise the foot and maintain balance in the medio-lateral
      direction, particularly during single leg stance.

PMID- 21864956
TI  - Transfer functions for solid-solution partitioning of cadmium for Australian
      soils.
AB  - To assess transport and ecotoxicological risks of metals, such as cadmium (Cd) in
      soils, models are needed for partitioning and speciation. We derived regression
      based "partition-relations" based on adsorption and desorption experiments for
      main Australian soil types. First, batch adsorption experiments were carried out
      over a realistic range of dissolved Cd concentrations in agricultural soils in
      Australia. Results showed linear sorption relationships, implying the adequacy of
      using Kd values to describe partitioning. Desorption measurements were then
      carried out to assess in-situ Kd values and relate these to soil properties The
      best transfer functions for solid-solution partitioning were found for Kd values
      relating total dissolved Cd concentration to total soil Cd concentrations,
      accounting for the variation in pH, SOM contents and DOC concentrations. Model
      predictions compared well with measurements of an independent data set, but there
      was a tendency to underestimate dissolved Cd concentrations of highly polluted
      soils.

PMID- 21864957
TI  - New DDT inputs after 30 years of prohibition in Spain. A case study in
      agricultural soils from south-western Spain.
AB  - This study provides information on the current status of contamination by DDT in
      agricultural soils in south-western Spain. A recent use of technical DDT in at
      least 17% of the soils was found based on the values (<1) of the ratio
      R(p,)(p')/(p,)(p') = [p, p'-DDE + p, p'-DDD]/[p, p'-DDT]. According to the ratio
      R0,(p')/(p,)(p') = [o, p'-DDT]/[p, p'-DDT] , a dicofol type contamination was
      detected in about 27% of the soils. A wide range of concentrations was observed
      (0.08-11.1 ng/g d.w.) regardless of the type of crop soil. Enantiomeric fractions
      (EFs), based on the chiral analysis of o,p'-DDT residues differed from the
      racemic value (0.500) in most soils but they were not correlated with the study
      variables [DDTs], SOM, R(p,)(p')/(p,)(p') and R0,(p')/(p,)(p'). Given the health
      risks posed by DDT, our findings support how the environmental control of legacy
      pollutants such as DDT cannot be neglected.

PMID- 21864958
TI  - Vertical distribution of hydrocarbons in the low troposphere below and above the
      mixing height: tethered balloon measurements in Milan, Italy.
AB  - A novel approach for measuring vertical profiles of HCs and particle number
      concentrations was described and applied in the low troposphere over Milan
      (Italy) during typical spring and summer days. Particle profiles yielded nearly
      homogeneous concentrations below the mixing height, with level-to-ground
      concentration ratios of 92-97%, while HCs showed a more pronounced decrease (74
      95%). Vertical mixing and photochemical loss of HCs were demonstrated to cause
      these gradients. Much lower concentrations were observed for the profiles above
      the mixing height, where the HC mixtures showed also a different composition,
      which was partially explained by the horizontal advection of air with HC sources
      different to those prevailing at the site. The application of pseudo-first order
      kinetics for reactions between HCs and the hydroxyl radical allowed for the
      estimation of the vertical mixing time scale in the order of 100 +/- 20 min.

PMID- 21864959
TI  - Assessment of organochlorine pesticide residues in Atlantic Rain Forest
      fragments, Rio de Janeiro, Brazil.
AB  - A superficial water quality survey in a watershed of the Paraiba do Sul River,
      the main water supply for the most populated cities of southeastern Brazil, was
      held in order to assess the impact of the expansion of agricultural activity in
      the near border of the Atlantic Rain Forest. The aim of this study was to
      investigate the presence of priority organochlorine pollutants in soils and
      superficial waters of Atlantic rainforest fragments in Teresopolis, Rio de
      Janeiro State. Soil sample preparations were compared by using ultrasound,
      microwave assisted extraction and Soxhlet extraction. Recoveries of matrix spiked
      samples ranged from 70 to 130%. Analysis of a certified soil material showed
      recoveries ranging from 71 to 234%. Although low concentrations of organochlorine
      residues were found in water and soil samples, this area is of environmental
      importance and concern, thus demanding a monitoring program of its compartments.

PMID- 21864960
TI  - Tissue distribution of Dechlorane Plus and its dechlorinated analogs in
      contaminated fish: high affinity to the brain for anti-DP.
AB  - Information on tissue distribution of Dechlorane Plus (DP) and its dechlorinated
      analogs in wildlife is scarce. DP isomers and two dechlorinated compounds, anti
      Cl(11)-DP and anti-Cl(10)-DP, were examined in the muscle, liver, and brain
      tissues of two bottom fish species collected from an electronic waste recycling
      site, South China. The median levels of syn-, anti-, and anti-Cl(11)-DP isomers
      in the tissues ranged 0.18-39.1, 0.22-52.9, and 0.01-5.63 ng/g wet wt,
      respectively. Anti-Cl(10)-DP was only detected in one muscle sample of mud carp
      (0.01 ng/g wet wt), although it was consistently detected in the sediments (0.42
      0.83 ng/g dry wt). Preferential distribution in liver relative to muscle was
      observed for syn-DP and anti-Cl(11)-DP. However, a high persistent retention in
      the brain compared to the liver was observed for anti-DP, suggesting that this
      isomer can across the blood-brain barrier of fish, and may cause adverse effects
      to the nervous system in the exposed biota.

PMID- 21864961
TI  - Nephrologists' perspectives on waitlisting and allocation of deceased donor
      kidneys for transplant.
AB  - BACKGROUND: Deceased donor kidneys are a scarce resource and there is debate
      about how to maximize the benefit from each donated kidney while ensuring equity
      of access to transplants. Allocation of kidneys to waitlisted patients is
      determined by a computer algorithm, but the decision to waitlist patients or
      accept the kidneys offered is largely at the discretion of nephrologists. This
      study aims to elicit nephrologists' perspectives on waitlisting patients for
      kidney transplant and the allocation of deceased kidneys. METHODS: We conducted
      semistructured face-to-face interviews with adult and pediatric nephrologists
      from 15 Australian nephrology or transplant centers. Transcripts were analyzed
      for descriptive and analytical themes. RESULTS: 25 nephrologists participated. 5
      major themes on waitlisting and deceased donor kidney allocation were identified:
      patient advocacy (championing their own patients, empowering patients, giving
      hope, individualizing judgments, patient preferences, and limited autonomy),
      professional and moral integrity (transparency, avoiding value judgments, and
      eliminating bias), protecting center reputation (gatekeeping), achieving equity
      (uniformity, avoiding discrimination, and fairness for specific populations), and
      maximizing societal benefit (prioritizing best use of kidney, resource
      implications, favoring social contribution, and improving efficiency of the
      allocation process). In making individual patient assessments, estimates about
      outcomes for a patient had to be resolved with whether it was reasonable from a
      broader societal perspective. CONCLUSION: Nephrologists expressed their primary
      responsibility in terms of giving their own patients access to a transplant and
      upholding professional integrity by maintaining transparency and avoiding value
      judgments and bias. However, nephrologists perceived an obligation to protect
      their center's reputation through the selection of "good" patients, and this
      caused some frustration. Despite having personal preferences for optimizing the
      balance between societal benefit and equity, nephrologists did not want direct
      responsibility for ensuring societal benefit in clinical practice. Rather, they
      placed the onus on policy makers and the community to reconcile such tensions and
      advocate for societal benefit.

PMID- 21864962
TI  - Erich Frank (1884-1957): unsung pioneer in nephrology.
AB  - The period between the 2 World Wars was a time of budding interest in renal
      studies and one that closed in major geopolitical unrest, culminating in World
      War II. The life of Erich Frank (1884-1957) and his contributions to chronic
      kidney disease provide considerable insight into this period. Frank began his
      career in Breslau, Germany. His medical thesis and first publication were on the
      benign nature of orthostatic proteinuria. He went on to define and differentiate
      essential from renal hypertension, presented evidence for the role of the
      posterior pituitary in diabetes insipidus, and studied the first oral
      hypoglycemic agent. As all clinical scientists then, Frank also contributed to
      other fields of medicine. When Germany turned to Nazism, Frank moved to Turkey,
      where he was appointed co-chair of the Department of Medicine of the newly
      established Istanbul University. For the next 23 years, he trained a new
      generation of modern physicians and laid the foundation of several medical
      disciplines in Turkey. As author of the first Turkish textbook of nephrology and
      a teacher who inspired his students, some of whom went on to become the first
      generation of Turkish nephrologists, Frank was a pioneer in nephrology who helped
      establish the discipline in his adopted country.

PMID- 21864963
TI  - Reproducibility of urinary albumin assays by immunonephelometry after long-term
      storage at -70 degrees C.

PMID- 21864964
TI  - Using matched areas to explore international differences in population health.
AB  - In this paper, we develop and test a method for examining the influence of
      national level contextual influences on population health. Acknowledging calls
      for the use of experimental study designs to explore contextual influences on
      health, we develop a study design in which sets of local areas from Britain and
      Belgium became akin to two 'treatment' groups; one exposed to British society and
      culture and the other exposed to Belgian society and culture. The areas are
      matched on the basis of showing very strong similarities in economic, demographic
      and historical characteristics. Data describing these characteristics are
      obtained from national census data. A principal component analysis of these
      variables permits areas in Britain and Belgium with similar scores on the
      resulting components to be matched into pairs. A sequence of logistic regression
      models identifies between-country difference in the risk of reporting poor
      health. Our final model compares the risk of reporting poor health among Belgians
      and people from Britain living in similar local contexts, adjusting for any
      residual differences in individual level characteristics. We compare results from
      this new method with those from more conventional approaches. All approaches show
      that residence in Britain is associated with a substantial and significantly
      higher risk of reporting poor health for both men and women, after adjustment for
      both individual and local contextual influences. We then critically reflect on
      our method and on the context-composition framework for research into area
      variation in health. We conclude that whilst our approach succeeded in applying
      the idea of comparable groups with different exposures to an observational,
      international comparison, it also brought associated questions about external
      validity and the extent to which a sample of matched areas captures a 'national'
      context.

PMID- 21864965
TI  - Comparing HIV-related symbolic stigma in six African countries: social
      representations in young people's narratives.
AB  - HIV-related symbolic stigma arises from moralistic value judgements attached to
      people living with HIV and has negative consequences from both public health and
      human rights perspectives. Relatively little is known about cross-national
      variation in symbolic stigma. With the purpose of informing stigma reduction
      efforts within and across settings, we compared social representations of HIV in
      six African countries with estimated adult HIV prevalence rates ranging from 1 to
      33%. Our study used a unique data source, namely a stratified random sample (n =
      586, ~5%) from 11,354 creative ideas contributed from six countries to a
      continent-wide HIV-related scriptwriting contest held between February and April
      2005. The narratives were written by equal numbers of males and females aged 10
      24 in urban and rural areas of Swaziland, Namibia, Kenya, South-East Nigeria,
      Burkina Faso and Senegal. We combined three analytical approaches: descriptive
      statistics on certain quantifiable characteristics of the narratives, thematic
      data analysis, and a narrative-based approach. The association of HIV with
      outsiders ("othering") and preoccupation with the circumstances of infection are
      more common in lower prevalence countries but vary substantially in tone
      depending on the sociocultural context. The highest proportion both of moralising
      narratives and of narratives with pessimistic outcomes come from South-East
      Nigeria and, to a lesser extent, from Kenya, countries with prevalence levels of
      3.9 and 6.1% respectively, in which evangelical Christian movements, including
      Pentecostalism, have sizeable followings. The data provide a rare cross-cultural
      overview of symbolic stigma, identify country-specific needs, and point to
      strategies for future programming. Social representations from the highest
      prevalence countries, Swaziland and Namibia, and from lower prevalence Burkina
      Faso offer potential models for the framing of HIV in ways that serve to increase
      social proximity and counteract symbolic stigma.

PMID- 21864966
TI  - Rhinocerebral mucormycosis: a diagnostic challenge and therapeutic dilemma in
      immunocompetent host.

PMID- 21864967
TI  - Correlation of increased twist with lymph node metastasis in patients with oral
      squamous cell carcinoma.
AB  - PURPOSE: To investigate the protein expression of Twist, Snail, and Slug in oral
      squamous cell carcinoma (OSCC) samples and evaluate the potential correlation
      between the expression status and clinicopathologic features in patients with
      OSCC. PATIENTS AND METHODS: Twist, Snail, and Slug protein expression was
      assessed by immunohistochemistry in a total of 60 OSCC samples and 10 normal oral
      mucosal samples. The associations between the protein expression and
      clinicopathologic parameters were mainly detected using the chi(2) test. The
      survival analysis was performed using the Kaplan-Meier method, and the prognostic
      analysis was performed using Cox regression models. RESULTS: Immunohistochemistry
      stain analysis showed that positive Twist, Snail, and Slug protein expression was
      observed in 70%, 63.3%, and 58.3% of the cases, respectively. Twist protein
      expression was positively associated with lymph node metastasis, pathologic
      grade, and tumor stage (P = .012, P = .008, and P = .004, respectively, chi(2)
      test). All patients were followed up for 6 to 59 months (mean 37). A correlation
      between Twist protein expression and tumor recurrence was detected (log-rank
      test, P = .025). Nevertheless, no correlation was found between the Snail and
      Slug protein expression and the clinicopathologic parameters. CONCLUSIONS: Twist
      might serve as a useful molecular marker for lymph node metastasis and a poor
      prognosis in OSCC.

PMID- 21864968
TI  - The effect of splinting implant-supported restorations on stress distribution of
      different crown-implant ratios and crown height spaces.
AB  - PURPOSE: To assess whether splinting can counterbalance the detrimental effects
      of varying the crown-to-implant (C/I) ratio and crown height space (CHS) by
      decreasing nonaxial overload stresses. MATERIALS AND METHODS: Three implants were
      inserted into a photoelastic block model. Two strain gauges were cemented onto
      the neck of each implant on the buccal and lingual aspects and provided a
      simultaneous direct reading of strain. Four groups of splinted cement-retained
      restorations with C/I ratios of 1:1, 1:1.5, 1:1.75, and 1:2 were used. CHSs were
      10, 15, 17.5, and 20 mm, respectively. Fifteen static loadings were carried out
      simultaneously with 20-kg weights via a custom-built loading apparatus at 30
      degrees  to the vertical axis. RESULTS: Occlusal force application at 30 degrees 
      showed a statistically significant increase in both buccal (1,911.65 +/- 110 vs
      3,252.06 +/- 150) and palatal (35.58 +/- 7 vs 286.85 +/- 15) microstrain values
      as the C/I ratio increased from 1:1 to 1:1.5 (P < .001). Force application at 30
      degrees  in cases with C/I ratios of 1:1.75 and 1:2 resulted in fracture of the
      abutment screw followed by dislodgement of the crowns. Failures were noted at a
      CHS of 15 mm or greater. CONCLUSIONS: In this biomechanical mode, splinting does
      not prevent prosthetic failure when the CHS is 15 mm or greater. Vertical bone
      augmentation is highly recommended in cases with a CHS of 15 mm or greater.

PMID- 21864969
TI  - Effect of removing an impacted mandibular third molar on the periodontal status
      of the mandibular second molar.
AB  - PURPOSE: The aim of this study was to evaluate the change in the periodontal
      status of mandibular second molars after surgical extraction of adjacent impacted
      lower third molars. MATERIALS AND METHODS: The study was based on a 1-year follow
      up of 48 patients (20 men and 28 women) recruited consecutively after the
      extraction of an impacted lower third molar. Panoramic radiographs were obtained
      and clinical examinations were carried out at baseline to determine the
      periodontal status (probing depth and dental plaque and gingival indices) both
      for the second molar and for the 4 posterior sextants. After surgical removal of
      the impacted mandibular third molars, all patients were assessed at 3, 6, 9, and
      12 months for changes in periodontal status. RESULTS: The periodontal health of
      the second molar was found to improve gradually after third molar surgery in all
      clinical parameters. Probing depth was gradually reduced by about 0.6 mm
      quarterly, until a final depth of 2.6 +/- 0.8 mm was attained. The relative risk
      of having a plaque index and gingival index coded as 0 (healthy) or 1 (minor
      problems) was about 10 times higher at the end of the follow-up than at baseline
      for both indices. The periodontal status of the 4 posterior sextants also
      improved gradually. Molar depth, according to the Pell and Gregory classes and
      types, seemed to be the main factor modulating both the baseline probing depth
      and the change in probing depth during follow-up. CONCLUSIONS: Our results
      suggest that the initial periodontal breakdown established on the distal surfaces
      of the second molars and in the periodontal health of the 4 posterior sextants
      can be significantly improved 1 year after surgical removal of the ipsilateral
      lower third molar.

PMID- 21864970
TI  - Orthognathic surgery in primary myopathies: severe case of congenital fiber type
      disproportion with long-term follow-up and review of the literature.

PMID- 21864971
TI  - Effect of platelet-rich plasma on growth and antigenic profile of human
      osteoblasts and its clinical impact.
AB  - PURPOSE: In recent years, there has been widespread clinical use of platelet-rich
      plasma (PRP) to facilitate the regeneration of different tissues. However, few
      data are available on the effect of PRP on parameters other than cell growth. The
      aim of the present study was to evaluate the effect of PRP on the cell cycle,
      antigenic profile, and proliferation of primary cultured human osteoblasts.
      MATERIALS AND METHODS: The cells in the present study were derived from human
      bone sections obtained from healthy volunteers during third molar surgery. PRP
      was prepared from human venous blood and used to culture the cell line obtained
      from the same patient. Flow cytometry was used to study the cell cycle, antigenic
      profile, and proliferation. RESULTS: The treatment of osteoblasts with PRP
      modified the expression of CD54, CD80, CD86, and HLA-DR antigens. PRP treatment
      increased cell proliferation in the short term, but the cell proliferation
      capacity diminished in the long term, perhaps owing to cell exhaustion. No change
      in the cell cycle profile was observed in the PRP-cultured cells. CONCLUSIONS:
      These results suggest that PRP treatment accelerates bone neoformation with no
      cell cycle changes that might carry a risk of malignant transformation.

PMID- 21864973
TI  - A binational, supply-side evaluation for managing water quality and invasive
      fouling species on California's coastal boats.
AB  - Integrated solutions are needed for sustainable management of risks posed by
      recreational boats to coastal water quality and ecosystems. Fouling organisms
      roughen vessel hull surfaces, creating friction that slows sailboats and
      increases fuel consumption by powerboats. Hull fouling control strategies for
      recreational boats that are stored in the water may include antifouling hull
      paints, newer alternative hull coatings, periodic in-water hull cleaning, and
      excluding propagules by surrounding the boat with a slip liner or raising it
      above water on a lift. Copper discharged to harbor waters from antifouling paints
      via passive leaching and in-water hull cleaning may elevate dissolved copper
      levels above government standards. Invasive species carried among boat-hull
      fouling organisms may be introduced as boats move among coastal areas. Some of
      these species tolerate copper in antifouling paints and copper-polluted harbor
      waters. Policy development must consider supply-side capacity, as well as
      economic and environmental sustainability, in managing these issues. This paper
      presents a supply-side evaluation useful in developing policies to co-manage
      water quality and invasive species risks for recreational boats navigating along
      the coasts of California, the Baja California peninsula and California's
      Sacramento-San Joaquin Delta. Supply-side perspectives on services, materials,
      costs, and boat owner behaviors, such as residence and travel patterns, awareness
      of hull-coating choices and selection of hull coatings, are determined. Analyses
      include evaluation of risks, risk management capacity and costs, and role of
      education in risk management. The issues raised are broadly applicable, as they
      are appearing on research and policy agendas in diverse coastal areas.

PMID- 21864974
TI  - P(4-vinyl pyridine) hydrogel use for the removal of UO(2)(2+) and Th(4+) from
      aqueous environments.
AB  - 4-vinyl pyridine (4-VP) based hydrogels with 2-hydroxyethylmetacrylate (HEMA) and
      magnetic composites were prepared and tested for use in the removal of UO(2)(2+)
      and Th(4+) ions from aqueous environments. It was found that the absorption of
      these metal ions from aqueous environments decreased with an increase in the
      amount of HEMA contained within p(4-VP-co-HEMA) hydrogels between 0.498 mmol for
      pure p(4-VP) and 0.027 mmol for pure p(HEMA). The characterization of the
      hydrogels was determined by swelling experiments, FT-IR and thermal analysis. The
      effects of initial metal ion concentration, hydrogel amount and the temperature
      of the medium on absorption of the ions were investigated. Langmuir and
      Freundlich isotherms were constructed for the absorption of UO(2)(2+) and Th(4+).
      Both isotherms demonstrated that these metal ions complied with monolayer
      absorption kinetics.

PMID- 21864972
TI  - Role of interleukins, IGF and stem cells in BPH.
AB  - The condition known as benign prostatic hyperplasia may be defined as a benign
      enlargement of the prostate gland resulting from a proliferation of both benign
      epithelial and stromal elements. It might also be defined clinically as a
      constellation of lower urinary tract symptoms (LUTSs) in aging men. The purpose
      of this review is to consider the ways in which inflammatory cytokines belonging
      to the interleukin family, members of the IFG family, and stem cells may
      contribute to the development and progression of BPH-LUTS. This might occur in
      three mechanisms: One, interleukin signaling, IFG signaling and stem cells may
      contribute to reactivation of developmental growth mechanisms in the adult
      prostate leading to tissue growth. Two, given that epidemiologic studies indicate
      an increased incidence of BPH-LUTS in association with obesity and diabetes, IFG
      signaling may provide the mechanistic basis for the effect of diabetes and
      obesity on prostate growth. Three, expression of interleukins in association with
      inflammation in the prostate may induce sensitization of afferent fibers
      innervating the prostate and result in increased sensitivity to pain and noxious
      sensations in the prostate and bladder and heightened sensitivity to bladder
      filling.

PMID- 21864975
TI  - Fabrication of WO3/Cu2O composite films and their photocatalytic activity.
AB  - WO(3)/n-Cu(2)O and WO(3)/p-Cu(2)O composite films have been fabricated on
      titanium (Ti) substrates with a consecutive cathodic electrodeposition route.
      Those resulting films were characterized with X-ray diffraction (XRD) and
      scanning electron microscopy (SEM). Their photocatalytic activity under simulated
      natural light illumination was evaluated using Orange II (mainly) and Cr(VI) as
      model pollutants. The results indicate that WO(3)/p-Cu(2)O exhibits higher
      photocatalytic activity compared to both WO(3) and p-Cu(2)O alone, while the
      photocatalytic activity of WO(3)/n-Cu(2)O is higher than WO(3), but lower than n
      Cu(2)O. Even in the absence of other reducing agents (hole scavengers), WO(3)/p
      Cu(2)O also show certain photocatalytic activity towards reduction of Cr(VI). The
      photocatalytic activity of WO(3)/p-Cu(2)O is closely related to the deposition
      amount of p-Cu(2)O. Additionally, WO(3)/p-Cu(2)O composite film also possesses a
      relatively high stability during the reactions. The difference in photocatalytic
      activity between the two types of composite films is interpreted in terms of
      different mechanisms for transfer of charge carriers photogenerated within the
      heterojunctions.

PMID- 21864976
TI  - Treatment of zinc-rich acid mine water in low residence time bioreactors
      incorporating waste shells and methanol dosing.
AB  - Bioreactors utilising bacterially mediated sulphate reduction (BSR) have been
      widely tested for treating metal-rich waters, but sustained treatment of mobile
      metals (e.g. Zn) can be difficult to achieve in short residence time systems.
      Data are presented providing an assessment of alkalinity generating media (shells
      or limestone) and modes of metal removal in bioreactors receiving a synthetic
      acidic metal mine discharge (pH 2.7, Zn 15 mg/L, SO(4)(2-) 200mg/L, net acidity
      103 mg/L as CaCO(3)) subject to methanol dosing. In addition to alkalinity
      generating media (50%, v.v.), the columns comprised an organic matrix of softwood
      chippings (30%), manure (10%) and anaerobic digested sludge (10%). The column
      tests showed sustained alkalinity generation, which was significantly better in
      shell treatments. The first column in each treatment was effective throughout the
      422 days in removing >99% of the dissolved Pb and Cu, and effective for four
      months in removing 99% of the dissolved Zn (residence time: 12-14 h). Methanol
      was added to the feedstock after Zn breakthrough and prompted almost complete
      removal of dissolved Zn alongside improved alkalinity generation and sulphate
      attenuation. While there was geochemical evidence for BSR, sequential extraction
      of substrates suggests that the bulk (67-80%) of removed Zn was associated with
      Fe-Mn oxide fractions.

PMID- 21864977
TI  - Application of aqueous two-phase systems for the development of a new method of
      cobalt(II), iron(III) and nickel(II) extraction: a green chemistry approach.
AB  - We have investigated the extraction behavior of the metallic ions Co(II), Fe(III)
      and Ni(II) as a function of the amount of potassium thiocyanate used as an
      extracting agent, using the following aqueous two-phase systems (ATPS): PEO +
      (NH(4))(2)SO(4) + H(2)O, PEO + Li(2)SO(4) + H(2)O, L35 + (NH(4))(2)SO(4) + H(2)O
      and L35 + (Li)(2)SO(4)+H(2)O. Metal extraction from the salt-rich phase to the
      polymer-rich phase is affected by the following parameters: amount of added
      extractant, pH, and the nature of the electrolyte and polymer that forms the
      ATPS. Maximal extraction percentages were obtained for Co(II) (99.8%), Fe(III)
      (12.7%) and Ni(II) (3.17%) when the ATPS was composed of PEO1500 +
      (NH(4))(2)SO(4) + H(2)O containing 1.4 mmol of KSCN at pH 4.0, providing
      separation factors as high as S(Co, Fe) = 3440 and S(Co, Ni) = 15,300. However,
      when the same ATPS was used at pH 2.0, the maximal extraction percentages for
      iron and nickel were 99.5% and 4.34%, respectively, with S(Fe, Ni) equal to 4380.
      The proposed technique was shown to be efficient in the extraction of Co(II) and
      Fe(III), with large viability for the selective separation of Co(II) and Fe(III)
      ions in the presence of Ni(II).

PMID- 21864978
TI  - Bacterial aox genotype from arsenic contaminated mine to adjacent coastal
      sediment: evidences for potential biogeochemical arsenic oxidation.
AB  - The potential biogeochemical redox activity of arsenic was investigated by
      examining bacterial arsenic (As) redox genes such as aox, ars, and arr in arsenic
      contaminated abandoned mine area and adjacent coastal sediments. Consistent with
      aerobic sediment and water samples from the mine through coastal areas, bacterial
      genes involing arsenic(V) (arsenate, AsO(4)(3-)) reduction such as arsC and arrA
      were identified only in a few samples, where's bacterial aoxB gene encoding
      arsenite oxidase which is a central role in arsenic(III) (AsO(2)(-)) oxidation of
      aox operon. This study suggests that evaluation of arsenite-oxidizing bacteria
      including aox genotype may lead to a better understanding of molecular
      geomicrobiology in arsenic biogeochemistry, which can be applied to the
      bioremediation of arsenic contaminated mines along the coast of Gwangyang Bay. In
      this study, high concentrations of arsenic were observed in the mines and
      Gwangyang Bay and it was speculated that As(III)-oxidizing bacteria isolated from
      those highly arsenic-contaminated areas contributed the biogeochemical cycling of
      arsenic by transforming arsenic species and resulting in change of mobility,
      though further in situ biogeochemical and/or microbial ecological investigations
      are needed for confirming the phenomena in natural environment. Acinetobacter
      junni and Marinobacter sp. which were isolated in the contaminated area contained
      the aox genes and were able to oxidize As(III) to As(V), which is a more soluble
      form in oxic aqueous environments and apt to migrate from the mine to the coast.
      This might suggest a potential of a significant redox role of aox genes of
      arsenic-oxidizing bacteria in biogeochemical cycle of arsenic.

PMID- 21864979
TI  - A role for the ventral hippocampal endocannabinoid system in fear-conditioned
      analgesia and fear responding in the presence of nociceptive tone in rats.
AB  - The endogenous cannabinoid (endocannabinoid) system plays an important role in
      fear-conditioned analgesia (FCA) and expression and extinction of conditioned
      fear. The hippocampus has an established role in both pain and conditioned fear
      and is a substrate for endocannabinoid activity. This study aimed to investigate
      the role of the endocannabinoid system in the ventral hippocampus (vHip) in FCA
      and in fear responding in the presence of nociceptive tone. Fear-conditioned rats
      displayed significantly increased freezing and 22-kHz ultrasonic vocalisation and
      a reduction in formalin-evoked nociceptive behaviour (ie, FCA) upon re-exposure
      to a context previously paired with footshock. Tissue levels of the
      endocannabinoids, anandamide, and 2-arachidonoylglycerol, as well as the fatty
      acid amide, palmitoylethanolamide, were significantly higher in the vHip of fear
      conditioned rats compared with non-fear-conditioned controls. URB597 (inhibitor
      of fatty acid amide hydrolase [FAAH]), administered bilaterally into the vHip,
      significantly enhanced FCA during the entire trial and increased fear responding
      in formalin-treated rats early in the trial. The URB597-induced enhancement of
      FCA was blocked by intra-vHip administration of the cannabinoid(1) (CB(1))
      receptor antagonist/inverse agonist rimonabant. Intra-vHip rimonabant alone had
      no effect on the expression of FCA, and URB597 did not significantly alter
      formalin-evoked nociceptive behaviour in non-fear-conditioned rats. These data
      suggest an important role for the endocannabinoid system in the vHip in FCA,
      whereby levels of 2-arachidonoylglycerol and the FAAH substrates
      palmitoylethanolamide and anandamide are increased in rats expressing FCA, and
      pharmacological inhibition of FAAH in the vHip enhances this form of endogenous
      analgesia via a CB(1) receptor-dependent mechanism.

PMID- 21864981
TI  - New strategy for the survey of Toxoplasma gondii in meat for human consumption.
AB  - Monitoring of Toxoplasma infection in animals destined for human consumption is a
      great challenge for human toxoplasmosis prevention. This study aimed to compare
      results obtained from a naturally infected population of sheep using different
      tests and targeting an original matrix: meat samples and muscle fluids collected
      at the slaughterhouse. A commercial ELISA test was performed on diaphragm fluids
      from 419 ovine carcasses collected at the slaughterhouse. A MAT (modified
      agglutination test) was performed on heart fluids obtained from the same animals.
      In addition, all hearts were bioassayed in mice. Serological test agreement, the
      relative sensitivity of ELISA MAT and mouse bioassay as well as a correlation
      between titres and parasite isolation probability were statistically evaluated.
      The overall agreement (kappa coefficient=0.64) of ELISA on diaphragm fluids and
      MAT on heart fluids is substantial and subsequently both tests can be used for
      epidemiological studies. Relative sensitivity was higher for MAT performed on
      cardiac fluids (90%) than ELISA on diaphragm fluid (61%). For both serological
      tests, relative sensitivity is lower in lambs younger than 12 months. Relative
      sensitivity of mouse inoculation was 42%. A significant correlation was obtained
      between increasing MAT titres and probability to isolate live parasite from the
      heart. When the fluid titre was higher than 1:16, parasites were isolated in 65%
      of cases. When it was lower, isolation failed in 95% of the cases. According to
      our results, cardiac fluids appear to be a relevant matrix for toxoplasmosis
      survey in meat.

PMID- 21864980
TI  - Early-life stress produces muscle hyperalgesia and nociceptor sensitization in
      the adult rat.
AB  - Chronic pain in adults has been associated with early-life stress. To examine the
      pronociceptive effect of early-life stress, we evaluated cutaneous and muscle
      nociception and activity in muscle nociceptors in an animal model of neonatal
      stress, limited bedding, in the rat. In this neonatal limited bedding (NLB)
      model, litters are exposed to limited bedding between postnatal days 2 and 9, and
      controls to standard bedding. In adult NLB-treated rats, mechanical nociceptive
      threshold in skeletal muscle was significantly lower (~22%) than in controls.
      Furthermore, administration of prostaglandin E(2) in skin as well as muscle
      produced markedly prolonged hyperalgesia, an effect prevented by spinal
      intrathecal injection of oligodeoxynucleotide antisense to protein kinase
      Cepsilon (PKCepsilon), a second messenger in nociceptors that has been implicated
      in the induction and maintenance of chronic pain. In electrophysiological
      studies, mechanical threshold of muscle nociceptors was reduced by ~31% and
      conduction velocity significantly increased (~28%). These findings indicate that
      neonatal stress induces a persistent hyperalgesia and nociceptor sensitization
      manifest in the adult and that the second messenger PKCepsilon may be a target
      against which therapies might be directed to treat a chronic pain syndrome that
      is associated with early-life traumatic stress.

PMID- 21864982
TI  - New insights into the epidemiology of bovine piroplasmoses in Italy.
AB  - Few studies have been published on bovine piroplasmoses in Italy, and therefore a
      clear picture of the epidemiology of these infections is difficult to obtain.
      Vertebrate and invertebrate hosts in Central and Northern Regions of Italy were
      investigated in 2005 and 2006, when microscopy, molecular tools and serological
      tests were applied to 468 blood samples drawn from cattle in order to evaluate
      the presence of these protozoa and identify possible risk factors. Ticks were
      also collected, identified and analyzed by molecular techniques. Microscopy
      identified 6.5% of the animals as positive, whereas PCR detected piroplasm DNA in
      21.6%. BLAST analysis showed 67 amplicons (17.0%) referable to the Theileria
      sergenti/buffeli/orientalis group, 17 (4.3%) to Theileria annae, and 1 to Babesia
      divergens. Serology evidenced a prevalence of 45.4% for Babesia bovis, 17.4% for
      Babesia bigemina, and 34.9% for B. divergens. The 127 collected ticks were
      identified as belonging to 5 species, mostly represented by Rhipicephalus bursa,
      Hyalomma marginatum and Ixodes ricinus. Molecular analyses evidenced the presence
      of B. bovis and B. bigemina, in 3 and 5 ticks, respectively. Our findings suggest
      that different species of piroplasms are circulating in bovine populations in
      Central and Northern Italy, and provide new insights into the complex
      epidemiology of bovine piroplasmoses in Italy.

PMID- 21864983
TI  - Parent-teen communication and pre-college alcohol involvement: a latent class
      analysis.
AB  - Although parent-adolescent communication has been identified as important in
      delaying the onset and escalation of alcohol use, both the strength and direction
      of observed associations have varied in prior research with adolescents and
      college students. The current study categorizes parents according to alcohol
      related communication and relates these categories to other parenting factors and
      late adolescent alcohol involvement. METHOD: As part of a larger study, 1007
      college-bound teens and their parents were assessed. Teens were asked to report
      on their drinking behavior, and parents were asked about the occurrence of
      several specific alcohol-related communications with their teen, as well as
      additional parenting characteristics. Profiles of parent alcohol-related
      communication were derived using latent class analysis. Once the best fitting
      solution was determined, covariates were entered predicting class membership and
      investigating how classes were associated with additional parenting
      characteristics and teen alcohol use. RESULTS: A five-class solution provided the
      best fit to the data: Frequent, All Topics (28%); Moderate, All Topics (25%);
      Frequent, General Topics (25%); Frequent, Consequences and Limits (12%); and
      Infrequent, All Topics (10%). Covariate analyses demonstrated class differences
      with regard to parental modeling, monitoring, knowledge, and parent-teen
      relationship satisfaction, as well as for students' intentions to join
      fraternities/sororities and alcohol use. CONCLUSIONS: Findings from the current
      study add to a small but growing literature supporting the continuing influence
      of parents in late adolescence and suggest that the frequency and specificity of
      parent-teen communication are potentially informative for refined parent-based
      preventive interventions.

PMID- 21864984
TI  - Drinking to enhance and to cope: a daily process study of motive specificity.
AB  - OBJECTIVE: Daily process studies of internal drinking motives have not examined
      motive specificity, i.e., whether theoretically plausible trait and situational
      antecedents differ in their ability to predict the extent to which alcohol
      consumption on any given day is motivated by coping or enhancement. METHOD:
      University students (N=81) completed trait measures of coping and enhancement
      motivated drinking (trait CM and EM), sensation seeking, and conscientiousness,
      and then completed a 14-day online diary assessing daily completion of tasks,
      daily alcohol use, and (on days when alcohol was consumed) the extent to which
      drinking was motivated by coping or enhancement (daily CM and EM). RESULTS:
      Hierarchical linear models revealed unique situational and trait antecedents of
      daily CM and EM. In the daily EM drinking model, main effects of daily positive
      affect (b=0.11, p<0.05), trait EM (b=2.88, p<0.01), and trait sensation seeking
      (b=0.36, p<0.01) were qualified by cross-level interactions between daily task
      accomplishment and trait conscientiousness (b=0.03, p<0.01), and daily task
      accomplishment and trait sensation seeking (b=0.03, p<0.01). In the daily CM
      drinking model, main effects of daily positive affect (b=-0.08, p<0.05), daily
      negative affect (b=0.13, p<0.05), and trait CM (b=4.40, p<0.01), were qualified
      by cross-level interactions between trait CM and daily positive affect (b=-0.12,
      p<0.05), trait CM and daily negative affect (b=0.18, p<0.01), and trait
      conscientiousness and daily task accomplishment (b=0.01, p<0.01). CONCLUSION: Our
      results replicated and extended Cooper et al.'s (1995) findings on the
      differential roles of sensation seeking and negative affect in CM and EM drinking
      at the daily level, and call into question the view that drinking motives should
      be solely conceptualized as individual difference variables. Theoretical and
      applied implications of the findings are discussed.

PMID- 21864985
TI  - Src inhibitors are promising therapy molecules for human cervical carcinomas.
AB  - Metastatic cervical cancer is a major cause of cancer mortality in women
      worldwide. In parallel, it is well established that high-risk human
      papillomaviruses (HPVs) are important factors in the progression of this cancer.
      Meanwhile, the overall 5 year-survival rate for patients diagnosed with cervical
      cancer is approximately 50% and has not significantly improved over the past two
      decades. Therefore, new strategies for the treatment of this cancer, especially
      the metastatic form, are becoming a major focus of investigation. Alternatively,
      Src family kinase activities are elevated in several human carcinomas, including
      cervical, and are often associated with aggressive cancer. Moreover, Src
      activities are deregulated by E6/E7 onco-proteins of high-risk HPV which are
      expressed in the majority of human cervical cancers. This raises the question
      whether Src inhibitors play a significant role in the treatment of human cervical
      carcinomas. In this paper, we propose the hypothesis that the Src family can be
      an important target for the treatment of this cancer. Although, we believe that
      significant studies, using different cells and animal models as well as clinical
      trails, are necessary to verify this hypothesis.

PMID- 21864986
TI  - Diuretics in Meniere disease: a therapy or a potential cause of harm?
AB  - Despite the lack of clear evidence for their effectiveness in treating vertigo,
      tinnitus, hearing loss and aural fullness, diuretics, represent a common
      treatment for Meniere disease (MD), as they are supposed to decrease volume and
      pressure in the endolymphatic partition of the labyrinth. Our group have outlined
      the possibility of an adverse effect on inner ear function derived from an abrupt
      lowering of blood pressure: a subsequent exaggerated vasomotor response inducing
      local ischemia could be responsible for more or less permanent damage. The inner
      ear, owing both to its terminal vascular supply and to the necessity of a steady
      metabolism, seems a reliable target for any hemodynamic imbalance that acutely
      affect its perfusion. In our opinion, the complexity of the inner ear anatomy and
      function argues against the usefulness of diuretics to reduce endolymphatic
      volume, in analogy to their effect on the volemia: too many active mechanisms and
      "buffer" systems are involved in the labyrinth. Even considering that the finding
      of mean low pressure values is relatively common in subjects with MD, an attempt
      should be to maintain a stable blood perfusion to the labyrinth; in fact, an
      abrupt decrease in systemic blood pressure can trigger an adverse sympathetic
      reaction and transmit misleading information to the cochlear vasopressin
      receptors.

PMID- 21864987
TI  - O6-methylguanine-DNA methyltransferase (MGMT): can function explain a suicidal
      mechanism?
AB  - Why does O(6)-methylguanine-DNA methyltransferase (MGMT), an indispensable DNA
      repair enzyme, have a mechanism which seems to run counter to its importance?
      This enzyme is key to the removal of detrimental alkyl adducts from guanine
      bases. Although the mechanism is well known, an unusual feature surrounds its
      mode of action, which is its so-called suicidal endpoint. In addition, induction
      of MGMT is highly variable and its kinetics is atypical. These features raise
      some questions on the seemingly paradoxical mechanism. In this manuscript we
      point out that, although there is ample literature regarding the "how" of the
      MGMT enzyme, we found a lack of information on "why" this specific mechanism is
      in place. We then ask whether we know all there is to know about MGMT, or if
      perhaps there is a further as yet unknown function for MGMT, or if the suicidal
      mechanism may play some kind of protective role in the cell.

PMID- 21864988
TI  - Born to yawn? Cortisol linked to yawning: a new hypothesis.
AB  - Yawning has become an interesting and curious scientific conundrum. Links between
      several neurological disorders can be found through the commonality of yawning
      episodes and contagious yawning. However, the reasons why we yawn are uncertain.
      Cortisol levels are known to rise during stress and fatigue; yawning may occur
      when we are under stress or tired. We do not know whether cortisol levels
      fluctuate during yawning. Potentially, yawning and cortisol levels may provide a
      valuable diagnostic tool and warning of untoward underlying neurological
      problems. A new hypothesis is proposed that links cortisol levels with yawning
      episodes.

PMID- 21864989
TI  - Anatomical consideration of the temporal bone as a pathogenesis of Bell's palsy.
AB  - Much controversy surrounds the etiology and management of Bell's palsy, and the
      pathogenetic mechanisms underlying Bell's palsy remain obscure despite the
      extensive body of relevant research. The pathological condition of Bell's palsy
      is almost an inflammatory reaction compressing the facial nerve in the fallopian
      canal, particularly in the narrowest labyrinthine segment, followed by
      demyelinating neural change. As one of the best method for the visualization of
      the inflamed facial nerve in the intratemporal segment, temporal bone CT enable
      us not only to measure the exact length and thickness of individual segments of
      the facial nerve canal but also to view variable anatomic variations in the
      intratemporal facial canal. Some suggest that anatomical variation may predispose
      the nerve to inflammatory processes and also there can be peculiar structures of
      the temporal bone that are vulnerable to inflammation or neural compression
      injury.

PMID- 21864990
TI  - Coronoid hyperplasia in chronic progressive trismus.
AB  - Hyperplasia of the coronoid process of the mandible has been observed in
      conditions like Oral submucous fibrosis, TMJ ankylosis, etc. The etiopathogenesis
      of this coronoid overgrowth has not been clearly sequenced or adequately
      hypothesized, and no definite mechanism has so far been advocated to explain this
      elongation of the coronoid process in the above mentioned conditions. Coronoid
      hyperplasia is seen in both these conditions despite being completely unrelated
      etiologically. However, progressive hypomobility of the mandible seems to be the
      common underlying condition in both the cases. We attempt to hypothesize a
      mechanism of coronoid hyperplasia, which appears to be independent of the
      underlying etiological factor causing trismus in these conditions.

PMID- 21864991
TI  - The possible role of AhR in the protective effects of cigarette smoke on
      preeclampsia.
AB  - Although smoking during pregnancy may lead to many adverse effects, such as fetal
      growth restriction, placental abruption, stillbirth, and preterm labor, smoking
      is the only environmental exposure known to consistently reduce the risk of
      preeclampsia and gestational hypertension. The exact mechanisms through which
      cigarette smoke reduces the risk of preeclampsia are not yet understood. Aryl
      hydrocarbon receptor (AhR), as the most abundant expression protein in the
      placenta, was widely studied in the human reproduction. We propose that cigarette
      smoke decreases the risk of developing preeclampsia via direct activation of AhR
      system in placenta. In this review we will address, and provide evidence for, our
      specific hypotheses that: cigarette significantly enhance trophoblast invasion
      and decrease placental oxidative damage through activation of AhR. This mechanism
      of suppression must be further investigated as they may provide valuable clues to
      novel therapeutic design in the realm of preeclampsia research.

PMID- 21864992
TI  - Local injection/induction of osteoclasts for the treatment of calcified
      tendinitis.
AB  - Calcified tendinitis is characterized by calcification in the rotary cuff tendon
      of the shoulder. The rationale of therapeutic methods is mainly removal of the
      calcification. Osteoclasts are the principle cells capable of resorbing bone and
      calcified tissues. Therefore, we hypothesized local injection of cultured human
      osteoclasts or induction of osteoclasts by recombinant RANKL in vivo may be
      effective for the treatment of calcified tendonitis. Human osteoclasts cultured
      in vitro is technically feasible and the osteoclasts are capable of active bone
      resorption. Thus, injection of osteoclasts may help remove the calcified
      tendonitis. In addition, human RANKL is commercially available. Therefore, local
      RANKL injection can recruit peripheral monocytes and macrophages. In the presence
      of RANKL, these monocytes and macrophages can subsequently differentiate into
      osteoclasts that can directly resorb calcification via their bone resorbing
      machinery. Different from the other treatments, the advantage of this therapeutic
      method includes: (1) less invasive because only local injection/induction of
      osteoclasts into the calcified lesion is conducted; (2) more efficient by direct
      osteoclasts injection or using RANKL to recruit osteoclasts to efficiently resorb
      calcification. Therefore, we proposed local injection/induction of osteoclasts as
      a potential biological method for clinical treatment of calcified tendinitis.

PMID- 21864993
TI  - Prognostic value of prevertebral space involvement in nasopharyngeal carcinoma
      based on intensity-modulated radiotherapy.
AB  - PURPOSE: To investigate the prognostic significance of prevertebral space
      involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with
      intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A retrospective
      review of data from 506 biopsy-proven, nonmetastatic NPCs was performed. Patients
      underwent magnetic resonance imaging examinations and received IMRT as their
      primary treatment. RESULTS: In this series, 161 NPC patients (31.8%) had PSI.
      Parapharyngeal space (p < 0.001), skull base (p < 0.001), and paranasal sinuses
      (p = 0.009) were associated with PSI after multivariate analysis. The 4-year
      overall survival (OS), local relapse-free survival (LRFS), distant metastasis
      free survival (DMFS) for NPC patients with and without PSI was 69.1% and 89.2% (p
      < 0.0001), 83.9% and 96.4% (p < 0.0001), and 71.6% and 89.6% (p < 0.0001),
      respectively. Multivariate analysis identified PSI as an independent negative
      prognostic factor for both OS (HR = 1.478-4.380; p = 0.001) and DMFS (HR = 1.389
      4.174; p = 0.002). Patients with PSI had similar survival rates in OS and DMFS (p
      = 0.241 and p = 0.493, respectively) to that of T4 disease, while the differences
      between PSI and T3 disease in both OS and DMFS were distinctly significant (p =
      0.029 and p = 0.029, respectively). CONCLUSIONS: For NPC patients treated with
      IMRT, PSI was found to be an independent prognostic factor for both OS and DMFS.
      It seems reasonable that PSI should be classified as a T4 disease on the basis of
      the current American Joint Committee on Cancer staging classification criteria.

PMID- 21864994
TI  - The dorsal horizon view: detecting screw protrusion at the distal radius.
AB  - PURPOSE: Extensor tendon injury after osteosynthesis of distal radius fractures
      is a well-documented complication. It has been shown to be associated with screw
      protrusion through the dorsal cortex, or plunging of the drill bit into the
      overlying tendon. It is difficult to determine screw length and protrusion using
      the standard anteroposterior and lateral intraoperative fluoroscopic images
      because of the triangular configuration of the distal radius and Lister tubercle.
      In fractures with a coronal split, it may be necessary to lag the dorsal
      fragment, necessitating longer screws and risking screw protrusion beyond the
      dorsal cortex. For these fractures, we use a radiographic view aimed along the
      long axis of the radius to detect screw protrusion. METHODS: This was a
      retrospective case series involving 15 distal radius fractures. To obtain the
      dorsal horizon view, the wrist is hyperflexed and the beam of the image
      intensifier is aimed along the long axis of the radius. We evaluated 15 distal
      radius fractures with a coronal split component, where the dorsal horizon view
      was used to detect dorsal cortex screw protrusion. This view was used
      intraoperatively following the use of the standard views. We evaluated records
      and imaging to ascertain whether the use of this radiograph led to a change in
      intraoperative screw selection. RESULTS: Of the 15 cases, we changed screw
      selection as a result of the additional view in 4 patients. In 3 of these cases,
      the screw length was long, which was not apparent on standard intraoperative
      fluoroscopic views. CONCLUSIONS: The use of the dorsal horizon view is a useful
      adjunct to prevent screw protrusion beyond the dorsal cortex when performing
      osteosynthesis of the distal radius.

PMID- 21864995
TI  - Potential dangers of tension band wiring of olecranon fractures: an anatomic
      study.
AB  - PURPOSE: Displaced olecranon fractures are often amenable to treatment with open
      reduction and tension-band wiring. The purpose of this study is to examine the
      relationships of the tips of K-wires used in a tension-band construct to volar
      neurovascular structures in the proximal forearm and the proximal radioulnar
      joint. METHODS: We performed simulated percutaneous pinnings of the proximal ulna
      under fluoroscopic guidance on 15 cadavers with intact proximal ulnas. The K
      wires were drilled obliquely through the tip of the olecranon process and
      directed to engage the anterior ulnar cortex, distal to the coronoid. Using
      calipers, we measured the distance from the tip of each pin to the anterior
      interosseous nerve (AIN), ulnar artery, proximal radioulnar joint (PRUJ), and
      volar cortex of the ulna, as well as the distance from the volar cortex of the
      ulna to the AIN and ulnar artery. The angle created by the K-wires and the
      longitudinal axis of the ulna was measured on both anteroposterior and lateral
      radiographs. RESULTS: The distance from pin tip to the AIN and ulnar artery
      measured a mean of 16 mm with a standard deviation of 6 mm and 14 mm with a
      standard deviation of 5 mm, respectively, with 1 pin abutting the artery. The
      shortest distance from both the AIN (11 +/- 5 mm) and the ulnar artery (8 +/- 6
      mm) was measured with the shallowest angle of insertion, ranging from 10 degrees 
      to 14.9 degrees  on lateral radiographs. The mean distance between the pin tip
      and the PRUJ measured 7 mm with a standard deviation of 4 mm, with 3 pins
      penetrating the PRUJ. CONCLUSIONS: The impaction of K-wires under the triceps is
      often approximately 1 cm, which is similar to the distance of the K-wire tips to
      the AIN and ulnar artery. Our findings suggest that larger insertion angles might
      help avoid neurovascular injury when the insertion point of the K-wires is at or
      just proximal to the tip of the olecranon. In this study, the safe zone for pin
      insertion on the anteroposterior view is 0 degrees  to 10 degrees , and on the
      lateral view it is 20 degrees  to 30 degrees . CLINICAL RELEVANCE: This anatomic
      study was done to diminish the chance of complications resulting from K-wire
      placement during tension-band wiring for olecranon fractures.

PMID- 21864996
TI  - Bdellovibrios, potential biocontrol bacteria against pathogenic Aeromonas
      hydrophila.
AB  - Recent studies have revealed that the use of bdellovibrios is an alternative to
      control bacteriosis. However, no bdellovibrios are available against Aeromonas
      hydrophila infections in sturgeons. In the present study, a potential
      Bdellovibrio strain F16 was isolated from sturgeon gut samples, using a sturgeon
      pathogenic A. hydrophila as the prey bacterium. It was initially identified as a
      Bdellovibrio strain using morphological characteristics and specific PCR
      amplification, and confirmed to be Bdellovibrio sp. strain ETB (GenBank Accession
      No. DQ302728) and Bdellovibrio bacteriovorus strain SRA9 (GenBank Accession No.
      AF263833) by phylogenetic analysis. In addition, it was shown to be safe for
      mammalians and sturgeons, had a wide prey range, and exhibited significant
      bacteriolytic effects on the pathogenic A. hydrophila. To the best of our
      knowledge, this is the first report on a promising gut Bdellovibrio strain
      against pathogenic A. hydrophila.

PMID- 21864997
TI  - Detection of virulence factors of Escherichia coli focused on prevalence of EAST1
      toxin in stool of diarrheic and non-diarrheic piglets and presence of adhesion
      involving virulence factors in astA positive strains.
AB  - Between 2005 and 2009, a total of 800 Escherichia coli strains isolated from
      piglets with diarrhea were tested for the presence of enteroaggregative heat
      stable enterotoxin EAST1, heat-labile (LT) and heat-stable enterotoxins (STa) and
      shigatoxin (Stx2e) by PCR with the purpose of investigating the present
      distribution of virulence factors on swine farms in the Czech Republic. The
      isolates were analyzed for their O-serogroup, fimbrial (K88, K99, 987P, F41, F18)
      and nonfimbrial adhesins (adhesin involved in diffuse adherence AIDA and porcine
      attaching and effacing-associated factor PAA). The detection rates of ETEC and
      STEC isolates were 36.5% and 7.75%, respectively, which implies that ETEC play
      the major role in E. coli infections in Czech herds. Generally, the most common
      serotype was O149:K88 which possessed genetic determinants for LT and EAST1. None
      of the tested E. coli isolates was positive for genes K99, 987P and F41. It was
      shown that out of 800 E. coli strains isolated from pigs, 277 were EAST1 positive
      and 74% from the latter were identified as ETEC. Of the fimbrial adhesins, K88
      and F18 were commonly detected. Over 80% of K88/EAST1 positive strains possessed
      the gene for paa. We detected no EAE isolate positive for fimbrial adhesins or
      PAA and AIDA. The AIDA was more often associated with F18 than with K88. The gene
      astA was also identified among E. coli isolates of non-diarrheic piglets. We
      tested rectal swab samples collected from apparently healthy piglets on three
      farms. On all farms, E. coli astA positive strains (26.66%, 90.00% and 46.66%
      astA positive animals) were isolated. Our results showed a significantly higher
      prevalence of astA positive E. coli isolates among apparently healthy piglets in
      comparison with diarrheic piglets. The question remains as to what is the role of
      the astA gene in the pathogenesis of porcine colibacillosis and as a virulence
      factor.

PMID- 21864998
TI  - Pneumocystis jirovecii colonization and infection among non HIV-infected
      patients.
AB  - OBJECTIVE AND METHOD: The epidemiology of pneumocystosis has changed in the last
      decade with a decreased incidence in HIV infected patients, and the emerging
      concept of Pneumocystis colonization. The study objective was to describe
      Pneumocystis infection as well as colonization among non-HIV infected patients in
      the Rouen teaching hospital and cancer institute. A retrospective study was made
      of all patients with a positive respiratory sample for Pneumocystis jirovecii
      between January 1, 2000 and June 6, 2007. RESULTS: Fifty-four cases were reported
      (46 cases of pneumocystosis and eight of asymptomatic carriage) and an increasing
      yearly incidence over the study period was observed. Underlying diseases for
      pneumocystosis were haematological malignancies (n=25; 54%), organ
      transplantation (n=8; 17.4%), inflammatory disorders (n=6; 13%), and solid cancer
      (n=5; 10.8%). Sixty-five per cent of patients were under long-term steroid
      therapy. The overall mortality rate was 21.4%. The CD4 count for 26 patients,
      ranged from 18 to 1449/mm(3) (median: 107). Eight cases of asymptomatic carriage
      were reported with an underlying immunodepression (n=6) and pulmonary disease
      (n=2). DISCUSSION: The increasing incidence of pneumocystosis in immunosuppressed
      patients without AIDS is due to more frequent favorable conditions and progress
      of diagnostic tools. The clinical presentations are severe. Prophylaxis is badly
      codified because there is no threshold value for CD4 count. Colonization could
      present a warning value.

PMID- 21864999
TI  - Magnetic resonance imaging features of nasopharyngeal carcinoma and
      nasopharyngeal non-Hodgkin's lymphoma: are there differences?
AB  - PURPOSE: To describe differences in the primary tumour and distribution of
      cervical lymphadenopathy for cases of nasopharyngeal carcinoma (NPC) and
      nasopharyngeal non-Hodgkin's lymphoma (NPNHL) using magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: MR images of patients with NPC (n = 272) and
      NPNHL (n = 118) were independently reviewed by two experienced radiologists.
      RESULTS: NPC had a higher incidence of tumour invasion associated with the
      levator and tensor muscles of the velum palatine, the longus colli and medial
      pterygoid muscles, the base of the pterygoid process, the clivus, the base and
      greater wing of the sphenoid bone, the petrous apex, the foramen lacerum, the
      foramen ovale, the hypoglossal canal, and intracranial infiltration. In contrast,
      NPNHL had a higher incidence of tumour invasion associated with the hypopharynx,
      the palatine and lingual tonsils, as well as the ethmoid and maxillary sinuses.
      NPNHL also had a higher incidence of extensive and irregular bilateral
      lymphadenopathy, and lymphadenopathy in the parotid. CONCLUSIONS: NPC more often
      involved an unsymmetrical tumour with a propensity to invade both widely and
      deeply into muscle tissue, the fat space, the neural foramen, and the skull base
      bone. In contrast, NPNHL tended to be a symmetrical and diffuse tumour with a
      propensity to spread laterally through the fat space and along the mucosa to the
      tonsils of the oropharynx and hypopharynx. These differences facilitate a
      differentiation of these diseases using MR images, and enhance our understanding
      of the biological behavior of these malignant tumours of the nasopharynx.

PMID- 21865000
TI  - Microwave-assisted forced degradation using high-throughput microtiter platforms.
AB  - Parallel microwave-assisted forced degradation in sealed HPLC/GC vials utilizing
      a high-throughput platform is described. The platform is made out of strongly
      microwave absorbing silicon carbide (SiC) plates providing 20 bore holes having
      the appropriate dimensions to be fitted with standard autosampler HPLC/GC vials
      serving as reaction vessels. Due to the possibility of heating up to four SiC
      platforms simultaneously (80 reactions) in a dedicated multimode microwave cavity
      with online temperature control, efficient parallel forced degradation studies
      can be performed at temperatures and pressures of up to 200  degrees C and 20
      bar, respectively. Since degradation reactions and analyses are performed in the
      same vessel, the sample handling effort is reduced and errors caused by a
      required transfer step are avoided. As proof-of-concept, the platform was
      evaluated for the parallel testing of various stress conditions on the drug
      indomethacin. The obtained data provided a rapid overview over suitable stress
      conditions at high temperatures, implicating a significant reduction in time
      required for the forced degradation compared to conventional methods at room
      temperature. Applying acidic (0.01-0.1 M HCl, 1-15 M AcOH), basic (0.001-0.01 M
      NaOH, 0.001-0.01 M NaHCO(3)) and oxidative (0.001-0.02% H(2)O(2)) stress
      conditions at 150  degrees C for 5 min resulted in similar indomethacin
      degradation levels requiring 0.5-20 h at lower temperatures (25-100  degrees C).
      In addition solvent stability tests exposing indomethacin to 20 different, mostly
      organic, solvents at 150  degrees C and 160  degrees C for 30 min and the
      exposure of the solid drug to various gases (N(2), Ar, O(2), NH(3), air),
      applying high temperatures are presented.

PMID- 21865001
TI  - Utility of multiplex reverse transcriptase-polymerase chain reaction for
      diagnosis and serotypic characterization of dengue and chikungunya viruses in
      clinical samples.
AB  - The reemergence of chikungunya virus (CHIKV) has compounded the already existing
      dengue problem because of clinical similarities and common vector, demanding the
      need for a rapid and specific diagnosis. Thus, dengue chikungunya multiplex
      reverse transcriptase-polymerase chain reaction (DCmRT-PCR) was developed and
      validated for simultaneous detection of dengue and chikungunya viral infections
      and its utility in virus serotyping. Blood samples from 97 suspected dengue and
      chikungunya cases and 10 healthy controls were subjected to dengue and
      chikungunya conventional RT-PCR and DCmRT-PCR. Thirty-one of 97 samples were
      positive for dengue or chikungunya viral RNA by RT-PCR and DCmRT-PCR with 100%
      concordance. DCmRT-PCR products were cycle sequenced. Seven dengue virus strains
      were clustered within genotype III of DENV-3 and 4 within genotype III of DENV-1,
      whereas chikungunya sequences were clustered within the Central/East African
      genotype. DCmRT-PCR was found to be a potential rapid test for simultaneous
      detection of dengue and CHIKV in clinical samples along with dengue serotyping.

PMID- 21865002
TI  - Post-antifungal effects and time-kill studies of anidulafungin, caspofungin, and
      micafungin against Candida glabrata and Candida parapsilosis.
AB  - Candida glabrata (Cgl) and Candida parapsilosis (Cpa) can cause serious
      infections and can be resistant to some antifungal drugs. In treating infections
      caused by these organisms, killing rates and post-antifungal effects (PAFE) are
      important factors in both dose interval choice and outcome. Two strains each of
      Cgl and Cpa were studied. For PAFE studies, each organism was exposed to
      micafungin (MCF), anidulafungin (ANF), or caspofungin (CAS) for 1 h at
      concentrations ranging from 0.25 to 16*MIC. Cell suspensions were then washed 3
      times and resuspended in fresh broth. Time 0 was immediately after resuspension
      of the yeast. Time-kill experiments were done using similar drug concentrations.
      Samples were removed at each time point (0-120 h) and viable counts determined.
      PAFE of ANF and CAS were generally very long, were markedly longer than those of
      MCF, and increased with increased drug concentration. For ANF and CAS, PAFE for
      Cgl were greater than those for Cpa only at 0.5 to 2 * MIC. Time-kill experiments
      showed that ANF, CAS, and MCF were fungicidal at 8 to 16 * MIC up to 120 h. CAS
      had the greatest activity against Cgl, while ANF and MCF were more active than
      CAS against Cpa. Because of the prolonged PAFE of these echinocandins, especially
      ANF and CAS, less frequent dosing during therapy of Cpa and Cgl infections could
      be considered. Further studies are needed to determine the clinical efficacy of
      longer dosing intervals.

PMID- 21865003
TI  - Locally acquired West Nile encephalitis.
AB  - BACKGROUND: West Nile virus (WNV) has spread rapidly across the United States
      since 1999, causing epidemics of neurologic illnesses including meningitis,
      encephalitis, and acute flaccid paralysis. West Nile encephalitis can be fatal;
      recovery can be incomplete; and constitutional and neurological symptoms can
      persist for months to years. OBJECTIVES: To raise awareness of an important
      epidemiologic cause of febrile illness with neurologic involvement in the United
      States. CASE REPORT: We report the case of a 46-year-old woman who presented with
      fever, altered mental status, and maculopapular rash, who was diagnosed with
      locally acquired WNV encephalitis. CONCLUSION: Infection with WNV should be
      considered in patients presenting to emergency departments with fever and
      neurologic symptoms. Recommended evaluation includes serologic testing of
      cerebrospinal fluid and serum.

PMID- 21865004
TI  - Traumatic fifth finger amputation due to pontoon boat railing design.
AB  - BACKGROUND: Boating is a common recreational activity that may subject its
      participants to specific patterns of injury. OBJECTIVES: We describe two
      unrelated cases of fifth-finger amputation associated with a specific pontoon
      boat guardrail design. CASE REPORT: The individuals in these cases sustained an
      avulsion-type amputation injury to the fifth finger when their fingers became
      entrapped in a narrowed portion of the boat railing before jumping into the
      water. CONCLUSIONS: Given the widespread use of this type of recreational boat,
      this apparent design flaw may place additional individuals at risk of significant
      hand injury with cosmetic and functional loss. Methods to reduce the public
      health impact of this type of injury are also discussed.

PMID- 21865005
TI  - Differential acute phase immune responses by Angus and Romosinuano steers
      following an endotoxin challenge.
AB  - Our primary objective of this experiment was to evaluate potential genetic
      differences between two diverse Bos taurus breeds [Angus (AG) and Romosinuano
      (RO)] in response to an endotoxin challenge. Eighteen steers (n = 9 steers/breed;
      299.4 +/- 5.2 kg BW) were acclimated to environmentally controlled chambers
      maintained at thermoneutrality (19.7  degrees C) and then fitted with indwelling
      jugular catheters and rectal temperature (RT) recording devices 1 d before the
      endotoxin challenge. The next day, blood samples were collected at 30-min
      intervals from -2 to 8 h, and RT was measured continuously at 1-min intervals
      throughout the study. At time 0, all steers received an intravenous bolus
      injection of lipopolysaccharide (LPS; 2.5 MUg/kg BW). Serum samples were stored
      at -80  degrees C until analyzed for cortisol, proinflammatory cytokines [tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), IL-6, and
      interferon gamma (IFN-gamma)], and acute phase proteins (serum amyloid A, acid
      soluble protein, ceruloplasmin, and alpha-acid glycoprotein). Rectal temperatures
      increased in both breeds within 1 h after LPS, with RO producing a greater
      increase in RT than AG steers (P < 0.001). Serum cortisol and TNF-alpha increased
      (P < 0.01) in both breeds within 1 h after the LPS challenge. For cortisol, an
      overall breed effect (P < 0.02) was detected, such that AG steers had a higher
      cortisol response than RO steers. A breed * time interaction (P < 0.01) was
      observed for TNF-alpha, such that the response was delayed and extended in the RO
      steers compared with the AG steers. At 2 and 2.5 h after LPS, TNF-alpha
      concentrations were greater (P < 0.03) in RO steers than in AG steers. For IL
      1beta, a breed * time interaction (P < 0.04) was also observed. At 3 h after LPS,
      IL-1beta concentrations were greater (P < 0.01) in RO steers than in AG steers.
      Serum IL-6 and IFN-gamma increased (P < 0.01) in a similar manner in both groups
      after the LPS challenge. These data show differences in the innate immune
      response between two diverse Bos taurus breeds which may provide insight about
      differences observed in productivity, heat tolerance, disease resistance, and
      longevity among cattle breeds.

PMID- 21865006
TI  - Infectious keratitis in 18,651 laser surface ablation procedures.
AB  - PURPOSE: To evaluate the incidence, culture results, risk factors, treatment
      strategies, and visual outcomes of infectious keratitis after surface ablation.
      SETTING: Multicenter study in Spain. DESIGN: Case series. METHODS: The medical
      records of patients who had surface ablation between January 2003 and December
      2009 were reviewed to identify cases of infectious keratitis. The incidence, risk
      factors, clinical course, days to diagnosis, medical and surgical treatment, and
      visual outcome were recorded. Main outcome measures were incidence of infectious
      keratitis after surface ablation, culture results, response to treatment, and
      visual outcomes. RESULTS: The study reviewed the records of 9794 patients (18,651
      eyes). Infectious keratitis after surface ablation was diagnosed in 39 eyes of 38
      patients. The onset of infection was early (within 7 days after surgery) in 28
      cases (71.79%). Cultures were positive in 13 of 27 cases in which samples were
      taken. The most frequently isolated microorganism was Staphylococcus species (9
      cases). The final corrected distance visual acuity (CDVA) was 20/20 or better in
      23 cases (58.97%), 20/40 or better in 36 cases (92.30%), and worse than 20/40 in
      3 cases (7.69%). CONCLUSIONS: The incidence of infectious keratitis after surface
      ablation was 0.20%. Infectious keratitis is a potentially vision-threatening
      complication. Prompt and aggressive management with an intensive regimen of
      fortified antibiotic agents is strongly recommended. Proper management can
      preserve useful vision in most cases. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 21865007
TI  - Residual astigmatism produced by toric intraocular lens rotation.
AB  - PURPOSE: To analyze changes in the eye's refractive properties when a toric
      intraocular lens (IOL) rotates. SETTING: Fundacion Oftalmologica del
      Mediterraneo, Valencia, Spain. DESIGN: Experimental study. METHODS: The matrix
      definition of astigmatism was used in this theoretical study and compared with
      another vector representation. Two methods were compared: (1) The cylinder, C,
      resulting from the addition of 2 cylinders C(1) and C(2) whose axes form an angle
      a, is obtained by the addition of 2 vectors of values C(1) and C(2) forming an
      angle 2a; (2) the power matrix, F, of a thin astigmatic dioptric system that
      decomposes naturally into 3 orthogonal components: the purely spherical part
      F(nes,) the ortho-astigmatism F(or), and oblique astigmatism F(ob). RESULTS: The
      residual cylinder was one third of the corneal astigmatism when a toric IOL
      rotated +/-10 degrees when the cylinder values for the cornea (C(1)) and IOL
      (C(2)) were equal. Nevertheless, in most cases C(1) is greater than C(2);
      therefore, the residual astigmatism did not change noticeably with small
      rotations. The angle of rotation, b, which annuls the astigmatism correction,
      could be obtained from the following: cos(pi + 2b) = -r/2, with r being the ratio
      between the IOL and cornea cylinders. CONCLUSIONS: The 2 methods gave equivalent
      results. When the IOL cylinder had a value different from that of the corneal
      astigmatism, a better choice would be a lower, rather than higher, cylinder value
      to reduce residual astigmatism. In general, toric IOL rotations less than 10
      degrees changed the eye's refraction less than 0.50 diopter. Thus, small axis
      rotations are not an obstacle for satisfactory astigmatism correction with toric
      IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in
      any material or method mentioned.

PMID- 21865008
TI  - Femtosecond-assisted keratopigmentation for functional and cosmetic restoration
      in essential iris atrophy.
AB  - We describe a new surgical technique of femtosecond-assisted keratopigmentation
      (KTP) in a 23-year-old woman with severe visual dysfunction secondary to
      unilateral essential iris atrophy due to the presence of iridocorneal endothelial
      syndrome in her left eye. The patient presented with complaints of photophobia
      and monocular diplopia in the affected eye. Femtosecond-assisted KTP surgery was
      performed in this eye. Following the procedure, the patient reported complete
      elimination of photophobia and diplopia, with an excellent cosmetic result.
      Follow-up of 12 months was unremarkable. To our knowledge, this is the first
      report of a severe visual function disability caused by essential iris atrophy
      that was corrected by a new KTP technique. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 21865009
TI  - Health information-seeking behaviors among classically trained singers.
AB  - Understanding health information-seeking behaviors (HISBs) within a particular
      patient demographic group is an important part of effective clinical outreach and
      education efforts. Although the community of classically trained singers has long
      been recognized by specialized health care providers, no studies have yet
      addressed the processes by which they search for voice-related health
      information, and little is known about how they use and access medical care. An
      electronic questionnaire focusing on HISB and voice-related health care issues
      was administered to 151 self-identified classically trained singers and 49
      nonsinger controls. Outcomes of interest were tested for association with groups
      of singers and controls, followed by tests of association between demographic
      variables (age, gender, insurance status) with each outcome of interest. Results
      showed significant differences in specialty care access including point of first
      contact (P=0.0085), gender-associated delay of treatment initiation (P=0.0324),
      and use of home remedies for vocal problems (P<=0.0001). Significant differences
      in HISB were noted as well, including history of having undertaken an information
      search (P<=0.0001), likelihood of having concerns about information quality
      (P<=0.0001), and difficulty knowing where to find information (P<=0.0001).
      Differences were influenced by singing status, age, and gender. The insights
      provided by these data may inform decision-making processes regarding patient
      care, patient education, and clinical outreach to the target population.

PMID- 21865010
TI  - New conditions on synchronization of networks of linearly coupled dynamical
      systems with non-Lipschitz right-hand sides.
AB  - In this paper, we study synchronization of networks of linearly coupled dynamical
      systems. The node dynamics of the network can be very general, which may not
      satisfy the QUAD condition. We derive sufficient conditions for synchronization,
      which can be regarded as extensions of previous results. These results can be
      employed to networks of coupled systems, of which, in particular, the node
      dynamics have non-Lipschitz or even discontinuous right-hand sides. We also give
      several corollaries where the synchronization of some specific non-QUAD systems
      can be deduced. As an application, we propose a scheme to realize synchronization
      of coupled switching systems via coupling the signals which drive the switchings.
      Examples with numerical simulations are also provided to illustrate the
      theoretical results.

PMID- 21865011
TI  - Validation of echocardiographic left atrial parameters in atrial fibrillation
      using the index beat of preceding cardiac cycles of equal duration.
AB  - BACKGROUND: The clinical assessment of left atrial function during atrial
      fibrillation is challenging and often inaccurate because of the beat-to-beat
      variability in the cycle length. The aim of this study was to validate the use of
      an index beat, the beat following two preceding cardiac cycles of equal duration,
      for the measurement of left atrial functional indices, including area, volume,
      and expansion index. The index beat was compared with the conventional but time
      consuming method of averaging multiple consecutive cardiac cycles. METHODS:
      Thirty patients with persistent or permanent atrial fibrillation were studied
      using two-dimensional echocardiography, and left atrial indices were measured
      from the average of 17 consecutive cardiac cycles compared with that of an index
      beat taken from outside of these 17 cycles. RESULTS: The index beat showed good
      correlation with the averaging technique, and comparison of the two methods
      showed them to be interchangeable. Clinically, the differences in left atrial
      functional indices between the two methods were minor. CONCLUSIONS: Use of the
      index beat to measure dynamic left atrial function in atrial fibrillation can
      easily be performed and is as accurate as and less time consuming than the
      onerous method of averaging of multiple cardiac cycles.

PMID- 21865012
TI  - Chronic rhinorrhea revealing an actinomycotic rhinolithiasis with ectopic tooth.
AB  - Intranasal ectopic tooth is a rare nidus for a rhinolith where local infection
      may be concomitant. No description of the triple association 'actinomycotic
      rhinolithiasis ectopic tooth' could be found in the medical literature.
      Classically, the Actinomyces species are sensitive to regimens of penicillin from
      6 to 12 months or longer. Immunocompetent patients can benefit from shorter
      courses of antibiotic therapy, such as ciprofloxacin, with a favourable outcome.
      The authors describe the case of a 25-year-old man who presented with an
      actinomycosis chronic discharge revealing actinomycosis associated with
      rhinolithiasis and ectopic tooth. They attempt to explain the likely mechanism of
      occurrence of this triple association.

PMID- 21865013
TI  - Lack of association between psychosis-like experiences and seeking help from
      professionals: a case-controlled study.
AB  - BACKGROUNDS: It still remains unclear whether individuals who experience
      attenuated psychotic symptoms are likely to seek help, whereas depressive
      symptoms are more likely to be associated with help-seeking behavior than these
      symptoms themselves. The aims of our study were to compare the profile of these
      symptoms between clinical and community samples and to investigate to what extent
      help-seeking behavior depends on the severity of psychosis-like symptoms and/or
      depressive symptoms. METHODS: The clinical sample consisted of help-seeking
      outpatients aged 16-30 years who had approached a community mental health clinic
      (N=750, mean age: 23.3+/-4.2 years, 62.4% females). The community sample was
      comprised of students from two universities and two high schools (N=781, mean
      age: 18.1+/-1.7 years, 59.2% females). Psychosis-like experiences were assessed
      using the PRIME Screen-Revised (PS-R), a self-reported screening instrument for
      assessing the risk of psychosis. Depressive symptoms were assessed using the Zung
      Self-rating Depression Scale (ZSDS), a 20-item self-reported questionnaire.
      RESULTS: Among the clinical and community samples, 27% and 10% had positive PS-R
      results respectively. No significant difference in the PS-R total score or the
      frequency of PS-R-positive items was observed between the clinical and community
      samples. A logistic regression analysis revealed that none of the psychosis-like
      experiences were significantly associated with help-seeking behavior, after
      controlling for the effect of depressive symptoms. CONCLUSIONS: Our findings
      showed that attenuated psychotic symptoms do not contribute significantly to help
      seeking behavior, suggesting that the relationships among PLEs, depressive
      symptoms, and help-seeking behavior should be reconsidered.

PMID- 21865014
TI  - Efficacy of a targeted cognitive-behavioral treatment program for cannabis use
      disorders (CANDIS).
AB  - AIMS: To examine the efficacy, 3- and 6-month follow-up effects of a
      psychological treatment for older adolescents and adults with DSM-IV cannabis use
      disorders. The program was tailored to the needs of this patient population.
      EXPERIMENTAL PROCEDURES: A randomized controlled clinical trial of 122 patients
      aged 16 to 44 years with DSM-IV cannabis dependence as the main substance use
      diagnosis was conducted. Patients were randomly assigned to either Active
      Treatment (AT, n = 90) or a Delayed Treatment Control group (DTC, n = 32).
      Treatment consisted of 10 sessions of therapy, detailed in a strictly enforced
      manual. Assessments were conducted at baseline, during each therapy session, at
      post treatment and at follow-up assessments at 3 and 6 months. RESULTS: The
      treatment retention rate was 88%. Abstinence was achieved in 49% of AT patients
      and in 13% of those in DTC (p < 0.001; intend-to-treat (ITT) analysis). Further,
      AT patients improved significantly (p < = 0.001) in the frequency of cannabis use
      per week, addiction severity, number of disability days, and overall level of
      psychopathology. Program effects were maintained over a 3-month- (abstinence
      rate: 51%) and 6-month follow-up (45%) period. CONCLUSION: The treatment program
      is effective in obtaining abstinence as well as reducing cannabis use and
      improves the associated social and mental health burden.

PMID- 21865015
TI  - Symptom relief and facilitation of emotional processing.
AB  - Symptoms and observable signs offer an important way of measuring the severity of
      depression and estimating recovery. However, a shift to understanding the
      cognitive neuroscience underlying the clinical picture has been fruitful and
      could change the approach in meaningful ways. Cognition as defined by attention,
      memory and executive function is impaired in depression and offers a way of
      identifying abnormal brain states or structure. Moreover, such changes may limit
      functional recovery and explain why recurrent depression in particular is so
      impairing. More subtle aspects of cognition can be revealed by studies of
      emotional processing. Patients with depression have negative emotional biases but
      the measurement of such effects is confounded by the global impairments already
      described and may be secondary to a primary change in mood. Nevertheless, there
      are early effects of antidepressants treatments in healthy volunteers and
      depressed patients on such mechanisms specifically. It remains to be established
      how far the properties of antidepressants are defined by such effects both in
      relation to successful treatment and in their potential for emotional side
      effects, or blunting of experience, after recovery from depressive symptoms.

PMID- 21865016
TI  - Treating depression: Diagnosing and treating circadian abnormalities in
      depression: current antidepressants.

PMID- 21865017
TI  - Solid lipid nanoparticles comprising internal Compritol 888 ATO, tripalmitin and
      cacao butter for encapsulating and releasing stavudine, delavirdine and
      saquinavir.
AB  - Solid lipid nanoparticles (SLNs) with complex internal phase were fabricated for
      formulating stavudine (D4T), delavirdine (DLV), and saquinavir (SQV). The lipids
      including Compritol 888 ATO, tripalmitin, and cacao butter were stabilized by L
      alpha-phospatidylcholine, cholesteryl hemisuccinate, and taurocholate to form
      SLNs. The results revealed that the morphology of SLNs was spheroidal with
      shallow surface pits. An increase in the weight percentage of Compritol 888 ATO
      increased the average diameter of D4T-entrapping SLNs and decreased that of DLV-
      and SQV-entrapping SLNs. Preservation at 4 degrees C over 6 weeks slightly
      enhanced the size of SLNs. For a specific drug, an increase in the entrapment
      efficiency enlarged the nanocarriers. The order of drug in the average particle
      diameter and in the entrapment efficiency was SQV>DLV>D4T, in general. In
      addition, the dissolution of the three drugs from SLNs showed the characteristics
      of sustained release. The order of drug in the cumulative release percentage was
      D4T>DLV>SQV. SLNs containing Compritol 888 ATO, tripalmitin, and cacao butter are
      efficient in carrying antiretroviral agents for medicinal application.

PMID- 21865018
TI  - [Thoracic congenital ectopic right kidney with diaphragmatic hernia: a rare
      developmental anomaly].
AB  - Ectopic intrathoracic kidney is a very rare congenital anomaly, which is often
      asymptomatic and discovered incidentally on chest radiography. Diagnosis of this
      ectopia in the neonatal period is extremely rare. We report the case of a female
      infant admitted for mild respiratory distress at birth in relation with
      maternofetal infection in whom a right posterior opacity on chest x-ray was
      diagnosed as intrathoracic kidney by sonography and chest CT scan. Diaphragmatic
      hernia could not be confirmed at this stage. At 2 months, the presence of air
      blebs on chest x-ray performed for viral bronchiolitis confirmed an associated
      right Bochdalek hernia. The infant, although asymptomatic, underwent surgery. The
      intrathoracic kidney was reduced into the abdominal cavity at the time of
      surgery. The postoperative course was uneventful and renal function was normal.

PMID- 21865019
TI  - Positron emission tomography scanning in oesophageal cancer - stuck at the first
      hurdle?

PMID- 21865020
TI  - Orchestrating the interferon antiviral response through the mitochondrial
      antiviral signaling (MAVS) adapter.
AB  - Sensing of RNA virus infection by the RIG-I-like receptors (RLRs) engages a
      complex signaling cascade that utilizes the mitochondrial antiviral signaling
      (MAVS) adapter protein to orchestrate the innate host response to pathogen,
      ultimately leading to the induction of antiviral and inflammatory responses
      mediated by type I interferon (IFN) and NF-kappaB pathways. MAVS is localized to
      the outer mitochondrial membrane, and has been associated with peroxisomes, the
      endoplasmic reticulum and autophagosomes, where it coordinates signaling events
      downstream of RLRs. MAVS not only plays a pivotal role in the induction of
      antiviral and inflammatory pathways but is also involved in the coordination of
      apoptotic and metabolic functions. This review summarizes recent findings related
      to the MAVS adapter and its essential role in the innate immune response to RNA
      viruses.

PMID- 21865021
TI  - Reference values for the incremental shuttle walking test.
AB  - BACKGROUND: Reference values for the incremental shuttle walking test (ISWT)
      which are applicable to the whole population need to be solidly established. This
      study aimed to determine which anthropometric and demographic variables influence
      the walking distance achieved in the ISWT in healthy subjects with a broad age
      range and to establish a reference equation for predicting ISWT for that
      population. METHODS: In a cross-sectional study, 242 healthy subjects (102 male)
      performed two ISWT and had their weight, height and body mass index (BMI)
      measured. RESULTS: In general, healthy subjects walked 810 [IQR 25-75%: 572-1030]
      m in the ISWT, presenting large variability (range 210-1820 m). The walked
      distance correlated with age (r = -0.76), height (r = 0.49) and BMI (r = -0.23)
      (p < 0.001 for all), but not with weight (r = 0.06, p = 0.315). A model of
      stepwise multiple regression showed that gender, age and BMI were independent
      contributors to the ISWT in healthy subjects, explaining 71% (p < 0.0001) of the
      variability. The derived reference equation was: ISWT(pred) = 1449.701 - (11.735
      * age) + (241.897 * gender) - (5.686 * BMI), where male gender = 1 and female
      gender = 0. CONCLUSION: In conclusion, the variability of the ISWT is explained
      largely by gender, age and BMI. The reference values for the ISWT can be
      adequately predicted using the equation proposed in this study.

PMID- 21865022
TI  - Time-effect of montelukast on protection against exercise-induced
      bronchoconstriction.
AB  - INTRODUCTION: Montelukast has been proven to assure a protective effect against
      exercise-induced bronchoconstriction. AIM: To verify exactly when montelukast
      begins protection in asthmatic children by evaluating different time intervals
      between dosing and challenge. METHODS: In a double blind, placebo-controlled,
      three day doses, crossover study, patients were randomized to receive in sequence
      treatment with either a placebo or montelukast and assigned to one of seven
      groups that were tested 1, 2, 3, 4, 5, 6 and 8 h after drug administration,
      respectively. For each group, the exercise challenge was always performed at the
      same hour on the first and third days of treatment. RESULTS: Sixty-nine asthmatic
      children took part in the study. On day 3, the mean FEV(1) % fall from baseline
      was 25.54 (95% CI = 21.63/29.46) and 14.89 (95% CI = 11.85/17.92) for the placebo
      and active drug (p < 0.05), respectively. On day 1, the mean fall of FEV(1) was
      28.20 (95% CI = 24.46/31.94) and 19.01 (95% CI = 15.71/22.31) for the placebo and
      montelukast (p < 0.05), respectively. Clinical protection was achieved in 21
      (30%) and 33 (48%) subjects by montelukast on the first and third days,
      respectively. CONCLUSIONS: Montelukast assured protection against exercise
      induced bronchoconstriction from the first through the eighth hour from the first
      day of treatment. However, individual susceptibility to protection was evident
      since some individuals were not protected at any time. We conclude that in
      clinical use individual responses to the drug should be carefully evaluated in
      the follow-up management.

PMID- 21865023
TI  - Pharmacogenomic determination of genes associated with sensitivity or resistance
      of tumor cells to curcumin and curcumin derivatives.
AB  - Curcuma longa L. has long been used as a medicinal plant in traditional Chinese
      medicine against abdominal disorders. Its active constituent curcumin has anti
      inflammatory, chemopreventive and cytotoxic properties. In the present
      investigation, we have analyzed the cytotoxic activity of curcumin and four
      derivatives. Among these compounds,
      ethoxycurcumintrithiadiazolaminomethylcarbonate was the most cytotoxic one. The
      curcumin-type compounds were not cross-resistant to standard anticancer drugs and
      were not involved in ATP-binding cassette transporter-mediated multidrug
      resistance. A combined approach of messenger RNA-based microarray profiling,
      COMPARE analyses and signaling pathway analyses identified genes as determinants
      of sensitivity and resistance to curcumin and specific signaling routes involved
      in cellular response to curcumin. These genes may be useful as biomarkers to
      develop individualized treatment options in the future. From a nutritional point
      of view, it is a thriving perspective to further investigate whether C. longa may
      be used as a spice to improve cancer therapy.

PMID- 21865024
TI  - Decline in extractable antibiotics in manure-based composts during composting.
AB  - A wide variety of antibiotics have been detected in natural water samples and
      this is of potential concern because of the adverse environmental effects of such
      antibiotic residues. One of the main sources of antibiotics effluence to the
      surrounding environment is livestock manures which often contain elevated
      concentrations of veterinary antibiotics (VAs) which survive digestion in the
      animal stomach following application in animal husbandry practices. In Korea,
      livestock manures are normally used for compost production indicating that there
      is potential for antibiotic release to the environment through compost
      application to agricultural lands. Therefore, reduction of the amount of VAs in
      composts is crucial. The purpose of this study was to understand the influence of
      the composting process and the components of the compost on the levels of three
      common classes of antibiotics (tetracyclines, sulfonamides, and macrolides).
      Composted materials at different stages of composting were collected from compost
      manufacturing plants and the variation in antibiotic concentrations was
      determined. Three different antibiotics, chlortetracycline (CTC), sulfamethazine
      (SMZ), and tylosin (TYL) at three different concentrations (2, 10, and 20mgkg(
      1)) were also applied to a mixture of pig manure and sawdust and the mixtures
      incubated using a laboratory scale composting apparatus to monitor the changes in
      antibiotic concentrations during composting together with the physicochemical
      properties of the composts. During composting, in both field and lab-scale
      investigations, the concentrations of all three different antibiotics declined
      below the relevant Korean guideline values (0.8mgkg(-1) for tetracyclines,
      0.2mgkg(-1) for sulfonamides and 1.0mgkg(-1) for macrolides). The decline of
      tetracycline and sulfonamide concentrations was highly dependent on the presence
      of sawdust while there was no influence of sawdust on TYL decline.

PMID- 21865025
TI  - Chemical and microbiological hazards associated with recycling of anaerobic
      digested residue intended for agricultural use.
AB  - In the present study, three full-scale biogas plants (BGP) were investigated for
      the concentration of heavy metals, organic pollutants, pesticides and the
      pathogenic bacteria Bacillus cereus and Escherichia coli in the anaerobically
      digested residues (ADR). The BGPs mainly utilize source-separated organic wastes
      and industrial food waste as energy sources and separate the ADR into an ADR
      liquid and an ADR-solid fraction by centrifugation at the BGP. According to the
      Norwegian standard for organic fertilizers, the ADR were classified as quality 1
      mainly because of high zinc (132-422 mg kg(-1) DM) and copper (23-93 mg kg(-1)
      DM) concentrations, but also because of high cadmium (0.21-0.60 mg kg(-1) DM)
      concentrations in the liquid-ADR. In the screening of organic pollutants, only
      DEHP (9.7-62.1 mg kg(-1)) and ? PAH 16 (0.2-1.98 mg kg(-1) DM) were detected in
      high concentrations according to international regulations. Of the 250 pesticides
      analyzed, 11 were detected, but only imazalil (<0.30-5.77 mg kg(-1) DM) and
      thiabendazol (<0.14-0.73 mg kg(-1) DM) were frequently detected in the ADR-fiber.
      Concentrations of imazalil and thiabendazol were highest during the winter
      months, due to a high consumption of citrus fruits in Norway in this period. Ten
      percent of the ADR-liquid samples contained cereulide-producing B. cereus,
      whereas no verotoxigenic E. coli was detected. The authors conclude that the risk
      of chemical and bacterial contamination of the food chain or the environment from
      agricultural use of ADR seems low.

PMID- 21865026
TI  - Can radiation therapy treatment planning system accurately predict surface doses
      in postmastectomy radiation therapy patients?
AB  - Skin doses have been an important factor in the dose prescription for breast
      radiotherapy. Recent advances in radiotherapy treatment techniques, such as
      intensity-modulated radiation therapy (IMRT) and new treatment schemes such as
      hypofractionated breast therapy have made the precise determination of the
      surface dose necessary. Detailed information of the dose at various depths of the
      skin is also critical in designing new treatment strategies. The purpose of this
      work was to assess the accuracy of surface dose calculation by a clinically used
      treatment planning system and those measured by thermoluminescence dosimeters
      (TLDs) in a customized chest wall phantom. This study involved the construction
      of a chest wall phantom for skin dose assessment. Seven TLDs were distributed
      throughout each right chest wall phantom to give adequate representation of
      measured radiation doses. Point doses from the CMS Xio(r) treatment planning
      system (TPS) were calculated for each relevant TLD positions and results
      correlated. There were no significant difference between measured absorbed dose
      by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up
      to 2.21% was found. The deviations from the calculated absorbed doses were
      overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a
      useful and accurate tool to assess the accuracy of surface dose. Our studies have
      shown that radiation treatment accuracy expressed as a comparison between
      calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately
      predicted for tangential treatment of the chest wall after mastectomy.

PMID- 21865027
TI  - Training breast care nurses throughout Europe: the EONS postbasic curriculum for
      breast cancer nursing.
AB  - BACKGROUND: The European Parliamentary Group on Breast Cancer and the European
      Society of Breast Cancer Specialists state that there is a need for EU agreed
      guidelines on breast care nursing and training. Therefore the European Oncology
      Nursing Society (EONS) commissioned the development of a post-basic curriculum
      for breast cancer nursing. PURPOSE: The goal was to define a European curriculum
      for the training of breast care nurses. METHODS: The curriculum was developed
      using a variety of sources, including guidelines from a number of European and
      other countries world wide, relevant literature and input from an expert panel of
      senior European nurses with expertise in breast care nursing. RESULTS: An English
      language, European curriculum of breast care nursing was developed at a postbasic
      level to provide guidance for the training of breast care nurses throughout
      Europe. Definitions for breast care nurse roles and activities and levels of
      practice, as well as indicative content are provided. CONCLUSIONS: The training
      of nurses in breast cancer care should be mandatory and common practice for
      European countries. To enhance comparability and standard development, the
      indicative content should be applied in all future post-basic education.

PMID- 21865028
TI  - Thermogravimetric investigation on co-combustion characteristics of tobacco
      residue and high-ash anthracite coal.
AB  - The thermal behavior of high-ash anthracite coal, tobacco residue and their
      blends during combustion processes was investigated by means of thermogravimetric
      analysis (20 K min(-1), ranging from ambient temperature to 1273 K). Effects of
      the mixed proportion between coal and tobacco residue on the combustion process,
      ignition and burnout characteristics were also studied. The results indicated
      that the combustion of tobacco residue was controlled by the emission of volatile
      matter; the regions were more complex for tobacco residue (four peaks) than for
      coal (two peaks). Also, the blends had integrative thermal profiles that
      reflected both tobacco residue and coal. The incorporation of tobacco residue
      could improve the combustion characteristics of high-ash anthracite coal,
      especially the ignition and burnout characteristics comparing with the separate
      burning of tobacco residue and coal. It was feasible to use the co-combustion of
      tobacco residue and high-ash anthracite coal as fuel.

PMID- 21865029
TI  - Comparative study for the effects of variable nutrient conditions on the
      biodegradation of microcystin-LR and concurrent dynamics in microcystin-degrading
      gene abundance.
AB  - Microcystin-LR (MCLR) degradation capability of biofilm was investigated with and
      without additional nutrients (nitrate, ammonium, peptone and glucose) at
      concentrations of 100 and 1000 mg L(-1). The MCLR-degradation was stimulated with
      nitrate and inhibited with other nutrients, except for that glucose of low
      concentration had no obvious effect. Both stimulatory and inhibitory effects
      enhanced with increasing concentration of corresponding nutrient. Quantitative
      polymerase chain reaction (qPCR) indicated that enhanced inhibition in
      biodegradation correlated to increased inhibition in functional gene (mlrA)
      abundance, as nutrient concentration increased. Stimulated biodegradation under
      low nitrate concentration may result from more rapid increase in mlrA gene
      abundance. These suggested that MCLR-degradation largely depended upon
      responsible bacterial population, which was affected by population of other
      bacteria in biofilm according to 16S rDNA-targeting qPCR. However, inhibited mlrA
      gene abundance implied that the stimulated biodegradation under high nitrate
      concentration might be involved in the mechanisms not related to MCLRDB
      population.

PMID- 21865030
TI  - Process and technoeconomic analysis of leading pretreatment technologies for
      lignocellulosic ethanol production using switchgrass.
AB  - Six biomass pretreatment processes to convert switchgrass to fermentable sugars
      and ultimately to cellulosic ethanol are compared on a consistent basis in this
      technoeconomic analysis. The six pretreatment processes are ammonia fiber
      expansion (AFEX), dilute acid (DA), lime, liquid hot water (LHW), soaking in
      aqueous ammonia (SAA), and sulfur dioxide-impregnated steam explosion (SO(2)).
      Each pretreatment process is modeled in the framework of an existing biochemical
      design model so that systematic variations of process-related changes are
      consistently captured. The pretreatment area process design and simulation are
      based on the research data generated within the Biomass Refining Consortium for
      Applied Fundamentals and Innovation (CAFI) 3 project. Overall ethanol production,
      total capital investment, and minimum ethanol selling price (MESP) are reported
      along with selected sensitivity analysis. The results show limited
      differentiation between the projected economic performances of the pretreatment
      options, except for processes that exhibit significantly lower monomer sugar and
      resulting ethanol yields.

PMID- 21865031
TI  - Biodegradation of tetrabromobisphenol A by oxidases in basidiomycetous fungi and
      estrogenic activity of the biotransformation products.
AB  - Tetrabromobisphenol A (TBBPA) degradation was investigated using white rot fungi
      and their oxidative enzymes. Strains of the Trametes, Pleurotus, Bjerkandera and
      Dichomitus genera eliminated almost 1 mM TBBPA within 4 days. Laccase, whose role
      in TBBPA degradation was demonstrated in fungal cultures, was applied to TBBPA
      degradation alone and in combination with cellobiose dehydrogenase from
      Sclerotium rolfsii. Purified laccase from Trametes versicolor degraded
      approximately 2 mM TBBPA within 5 h, while the addition of cellobiose
      dehydrogenase increased the degradation rate to almost 2.5 mM within 3 h. Laccase
      was used to prepare TBBPA metabolites 2,6-dibromo-4-(2-hydroxypropane-2-yl)
      phenol (1), 2,6-dibromo-4-(2-methoxypropane-2-yl) phenol (2) and 1-(3,5-dibromo-4
      hydroxyphen-1-yl)-2,2',6,6'-tetrabromo-4,4'-isopropylidene diphenol (3). As
      compounds 1 and 3 were identical to the TBBPA metabolites prepared by using rat
      and human liver fractions (Zalko et al., 2006), laccase can provide a simple
      means of preparing these metabolites for toxicity studies. Products 1 and 2
      exhibited estrogenic effects, unlike TBBPA, but lower cell toxicity.

PMID- 21865032
TI  - Application of hemicelluloses precipitated via ethanol treatment of pre
      hydrolysis liquor in high-yield pulp.
AB  - Hemicelluloses in industrially produced pre-hydrolysis liquor (PHL) were
      precipitated with ethanol. These PHL-derived hemicelluloses (PHL-EH) and a
      commercial, pure birch wood xylan sample (powder form) (BWX) were bleached using
      chlorine dioxide (D(0) and D(1)) and hydrogen peroxide (Ep) in the D(0)EpD(1)
      sequence, and the chemical compositions, molecular weights and charge densities
      of the treated samples were assessed. When applied to high-yield pulp (HYP) at 50
      mg/g, 26 and 20 mg/g of the bleached PHL-EH and BWX, respectively, were adsorbed
      without significantly affecting paper properties. These results suggest that semi
      bleached hemicelluloses could be used to increase the basis weight of paper
      products. Furthermore, an integrated process was proposed that converts the kraft
      based dissolving pulp production process into a biorefinery unit with dissolving
      pulp, bleached hemicelluloses and lignin as main products.

PMID- 21865033
TI  - Role of vermicompost chemical composition, microbial functional diversity, and
      fungal community structure in their microbial respiratory response to three
      pesticides.
AB  - The relationships between vermicompost chemical features, enzyme activities,
      community-level physiological profiles (CLPPs), fungal community structures, and
      its microbial respiratory response to pesticides were investigated. Fungal
      community structure of vermicomposts produced from damaged tomato fruits (DT),
      winery wastes (WW), olive-mill waste and biosolids (OB), and cattle manure (CM)
      were determined by denaturing gradient gel electrophoresis of 18S rDNA.
      MicroRespTM was used for assessing vermicompost CLPPs and testing the microbial
      response to metalaxyl, imidacloprid, and diuron. Vermicompost enzyme activities
      and CLPPs indicated that WW, OB, and DT had higher microbial functional diversity
      than CM. The microbiota of the former tolerated all three pesticides whereas
      microbial respiration in CM was negatively affected by metalaxyl and
      imidacloprid. The response of vermicompost microbiota to the fungicide metalaxyl
      was correlated to its fungal community structure. The results suggest that
      vermicomposts with higher microbial functional diversity can be useful for the
      management of pesticide pollution in agriculture.

PMID- 21865034
TI  - Anaerobic digestion and co-digestion processes of vegetable and fruit residues:
      process and microbial ecology.
AB  - This study evaluated the feasibility of methane production from fruit and
      vegetable waste (FVW) obtained from the central food distribution market in
      Mexico City using an anaerobic digestion (AD) process. Batch systems showed that
      pH control and nitrogen addition had significant effects on biogas production,
      methane yield, and volatile solids (VS) removal from the FVW (0.42
      m(biogas)(3)/kg VS, 50%, and 80%, respectively). Co-digestion of the FVW with
      meat residues (MR) enhanced the process performance and was also evaluated in a
      30 L AD system. When the system reached stable operation, its methane yield was
      0.25 (m(3)/kg TS), and the removal of the organic matter measured as the total
      chemical demand (tCOD) was 65%. The microbial population (general Bacteria and
      Archaea) in the 30 L system was also determined and characterized and was closely
      correlated with its potential function in the AD system.

PMID- 21865035
TI  - Characterizing membrane foulants in MBR with addition of polyferric chloride to
      enhance phosphorus removal.
AB  - The effect of polymeric ferric chloride (PFC) addition on phosphorus removal and
      membrane fouling were investigated in an anoxic/oxic submerged membrane
      bioreactor. The total phosphorus concentration in effluent averaged at 0.26 mg/L
      with PFC addition of 10-15 mg/L, while the rate of membrane fouling increased 1.6
      times over the control MBR (without PFC addition). Three-dimensional excitation
      emission matrix fluorescence spectroscopy and Gel Filtration Chromatography
      analysis indicated that soluble microbial byproduct-like materials and large
      molecules (M(W)>100 kDa) were one of the main contributors of biofouling. Fourier
      transform infrared spectrum confirmed that the major components of the cake layer
      were proteins and polysaccharides materials. Scanning electron microscopy
      demonstrated that membrane surfaces were covered with compact gel layer formed by
      organic substances and Energy Dispersive X-ray analysis indicated that ferric
      metals were the most important inorganic pollutants. Consequently, soluble
      organic substances and dose of PFC should be controlled to minimize membrane
      fouling.

PMID- 21865036
TI  - Self-induced bio-potential and graphite electron accepting conditions enhances
      petroleum sludge degradation in bio-electrochemical system with simultaneous
      power generation.
AB  - Bio-electrochemical treatment (BET) documented effective degradation of real
      field petroleum sludge over the conventional anaerobic treatment (AnT). BET
      (41.08%) operation showed enhanced total petroleum hydrocarbons (TPH) removal
      over AnT (20.72%). Aromatic fraction visualized higher removal (75.54%) compared
      to other TPH fractions viz., aliphatics, asphaltenes and NSO (nitrogen, sulfur
      and oxygen) during BET operation. Higher ring aromatics (5-6) documented easy
      degradation in BET, while AnT was limited to lower ring (2-3) compounds.
      Voltammetric analysis evidenced simultaneous redox behavior during BET operation
      due to presence of graphite electrode as electron acceptor, while AnT showed
      extended reduction behavior only. Self-induced primary and secondary oxidation
      reactions and capacitive-deionization might have enhanced the degradation
      capability of BET. BET documented higher charge/capacitance (2810 mJ/1120 mF)
      than AnT (450 mJ/180 mF). Power output corroborated well with observed results
      supporting BET performance as fuel cell. Electrodes offer a potential alternative
      electron acceptor for promoting the degradation of organic contaminants.

PMID- 21865037
TI  - Ammonium as a sustainable proton shuttle in bioelectrochemical systems.
AB  - This work examines a pH control method using ammonium (NH(4)(+)) as a sustainable
      proton shuttle in a CEM-equipped BES. Current generation was sustained by adding
      NH(3) or ammonium hydroxide (NH(4)OH) to the anolyte, controlling its pH at 7.
      Ammonium ion migration maintained the catholyte pH at approximately 9.25. Such
      NH(4)(+)/NH(3) migration accounted for 90+/-10% of the ionic flux in the BES.
      Reintroducing the volatilized NH(3) from the cathode into the anolyte maintained
      a suitable anolyte pH for sustained microbial-driven current generation. Hence,
      NH(4)(+)/NH(3) acted as a proton shuttle that is not consumed in the process.

PMID- 21865038
TI  - Fuscoside E: a strong anti-inflammatory diterpene from Caribbean octocoral
      Eunicea fusca.
AB  - The screen of 10 soft coral extracts collected from the Colombian Caribbean Sea
      in the TPA-induced ear edema model allowed us to identify Eunicea fusca extract
      among others as an interesting source of active compounds. The new diterpene,
      fuscoside E (1), along with the known fuscoside B (2), fuscol (3), (+)-germacrene
      D (4) and a mixture of six sterols (5-10), were isolated from this soft coral.
      Their structures were elucidated by 1D and 2D NMR spectroscopy techniques.
      Fuscoside E (1) absolute stereochemistry was determined by chiroptical methods.
      Fuscoside E (1) and B (2) showed strong anti-inflammatory in the above mentioned
      bioassay. Additionally, fuscoside E (1) and the sterol mixture (5-10) presented
      antifouling activity against bacterial strains involved in surface colonization.

PMID- 21865039
TI  - Synthesis of phenanthroindolizidine alkaloids and evaluation of their antitumor
      activities and toxicities.
AB  - We previously reported that phenanthroindolizidine alkaloid 3 and its derivatives
      had markedly potent in vitro cytotoxicity. However, they had low in vivo
      antitumor activities and high in vivo toxicities, which was a serious problem. To
      address this problem, new phenanthroindolizidine derivatives were synthesized and
      their antitumor activities and toxicities were evaluated. This study describes
      the relationship between the chemical structures, antitumor activities, and
      toxicities of these phenanthroindolizidine derivatives. Based on its properties,
      compound 8 was found to be the most suitable potential antitumor agent.

PMID- 21865041
TI  - Synthesis of deuterium labeled ketamine metabolite dehydronorketamine-d4.
AB  - A convenient synthesis of ketamine metabolite dehydronorketamine-d(4), starting
      from commercially available deuterium labeled bromochlorobenzene, was achieved.
      Key steps include Grignard reaction, regioselective hydroxybromination,
      Staudinger reduction, and dehydrohalogenation.

PMID- 21865040
TI  - Histone deacetylase activators: N-acetylthioureas serve as highly potent and
      isozyme selective activators for human histone deacetylase-8 on a fluorescent
      substrate.
AB  - We report, for the first time, that certain N-acetylthiourea derivatives serve as
      highly potent and isozyme selective activators for the recombinant form of human
      histone deacetylase-8 in the assay system containing Fluor-de-Lys as a
      fluorescent substrate. The experimental data reveals that such activating feature
      is manifested via decrease in the K(m) value of the enzyme's substrate and
      increase in the catalytic turnover rate of the enzyme.

PMID- 21865042
TI  - Preparation and antibacterial evaluation of decarboxylated fluoroquinolones.
AB  - Decarboxylated ciprofloxacin (3) has been reported in the literature to have
      antibacterial activities against Staphylococcus aureus, Staphylococcus
      epidermidis, Enterococcus faecalis, Bacillus subtilis, Enterobacter cloacae,
      Serratia marcescens and especially potent activity against Escherichia coli.
      Herein, we report our syntheses of 3 and five additional decarboxylated
      fluoroquinolones (FQs). We have re-evaluated the antibacterial activity of these
      FQs. In contrast to previously reported data, none of these decarboxylated
      fluoroquinolones showed significant antibacterial activity in our assays using
      both the broth dilution and agar methods. Our study confirmed that the presence
      of a carboxylic acid group at the 3-position of the fluoroquinolone scaffold is
      essential for antibacterial activity.

PMID- 21865043
TI  - Characteristics and outcomes according to molecular subtypes of breast cancer as
      classified by a panel of four biomarkers using immunohistochemistry.
AB  - To investigate the significance of immunohistochemical molecular subtyping, we
      evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone
      receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using
      tissue microarrays, 1006 breast cancer patients between November 1999 and August
      2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67
      < 14%), luminal B (ER+ and/or PR+, HER2-, Ki-67 >= 14% or ER+ and/or PR+, HER2+),
      HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-,
      PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively
      analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched,
      and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively.
      Luminal A presented well-differentiation and more co-expression of hormone
      receptors comparing to luminal B. HER2-enriched showed larger size and higher
      nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size,
      undifferentiation, higher proliferation, and frequent visceral metastases. The
      peak of recurrence for luminal A was at 36 months postoperatively, while that for
      HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was
      mixed. Luminal A showed the best survival, but no difference was observed between
      the other three subtypes. When matched by nodal status, however, TNBC showed the
      worst outcomes in node-positive patients. In multivariate analyses, luminal A
      remained a positive prognostic significance. Immunohistochemically-defined
      subtypes showed different features, recurrence patterns, and survival. Therefore,
      molecular subtypes using four biomarkers could provide clinically useful
      information of tumor biology and clinical behaviors, and could be used for
      determining treatment and surveillance strategies.

PMID- 21865044
TI  - Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external
      breast radiotherapy for breast cancer: a randomized trial.
AB  - Persistent pain after breast cancer treatment (PPBCT) affects between 25 and 60%
      of patients depending on surgical and adjuvant treatment. External breast
      radiotherapy (EBRT) has been shown to be a riskfactor for PPBCT, raising the
      question whether intraoperative radiation therapy (IORT), with its smaller
      radiation field may reduce the development of PPBCT. Using data from the TARGIT-A
      trial, the aim of this study was to compare these two treatments with regard to
      development of PPBCT. A total of 281 patients enrolled in the TARGIT-A trial from
      the Copenhagen University Hospitals was screened for participation, and a total
      of 244 patients were included and received a detailed questionnaire. The response
      rate was 98%, leaving 238 patients for the final analysis. Pain prevalence were
      33.9% in the EBRT group and 24.6% in the IORT group (p = 0.11). Treatment with
      IORT may not alter the risk of PPBCT.

PMID- 21865045
TI  - High-voltage electrical burn of the skull causing thrombosis of the superior
      sagittal sinus.
AB  - We aimed to describe the effects of high-voltage electricity on the scalp,
      meninges, brain parenchyma, and venous sinuses of a 10-year-old girl with an
      accidental high-voltage electrical burn of the head who presented with an area of
      full-thickness scalp loss. Magnetic resonance venography demonstrated that the
      anterior third of the superior sagittal sinus was thrombosed. The child underwent
      surgical debridement of the wound with a duraplasty and transposition scalp-flap
      reconstruction. She recovered well after surgery. Our patient had no neurological
      deficit at presentation, and she had no new deficit at her 6-month follow-up
      examination. We concluded that despite the electrical nature of the brain, direct
      neural injury is largely thermal. To our knowledge, a scalp burn deep enough to
      involve the superior sagittal sinus has not been reported. Physicians must be
      aware of the potential for delayed neurological deterioration, including severe
      deficits such as quadriplegia.

PMID- 21865046
TI  - Isolation, identification, and biological evaluation of HIF-1-modulating
      compounds from Brazilian green propolis.
AB  - The tumor microenvironment is characterized by hypoxia, low-nutrient levels, and
      acidosis. A natural product chemistry-based approach was used to discover small
      molecules that modulate adaptive responses to a hypoxic microenvironment through
      the hypoxia-inducible factor (HIF)-1 signaling pathways. Five compounds, such as
      baccharin (3), beturetol (4), kaempferide (5), isosakuranetin (6), and drupanin
      (9), that modulate HIF-1-dependent luciferase activity were identified from
      Brazilian green propolis using reporter assay. Compounds 3, 9 and 5 reduced HIF-1
      dependent luciferase activity. The cinnamic acid derivatives 3 and 9
      significantly inhibited expression of the HIF-1alpha protein and HIF-1 downstream
      target genes such as glucose transporter 1, hexokinase 2, and vascular
      endothelial growth factor A. They also exhibited significant anti-angiogenic
      effects in the chick chorioallantoic membrane (CAM) assay at doses of 300 ng/CAM.
      On the other hand, flavonoids 4 and 6 induced HIF-1-dependent luciferase activity
      and expression of HIF-1 target genes under hypoxia. The contents (g/100g extract)
      of the HIF-1-modulating compounds in whole propolis ethanol extracts were also
      determined based on liquid chromatography-electrospray ionization mass
      spectrometry as 1.6 (3), 14.2 (4), 4.0 (5), 0.7 (6), and 0.7 (9), respectively.
      These small molecules screened from Brazilian green propolis may be useful as
      lead compounds for the development of novel therapies against ischemic
      cardiovascular disease and cancer based on their ability to induce or inhibit HIF
      1 activity, respectively.

PMID- 21865047
TI  - 6,7-Dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines and their derivatives as
      novel corticotropin-releasing factor 1 receptor antagonists.
AB  - To identify an orally active corticotropin-releasing factor 1 receptor
      antagonist, a series of 6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines
      and their derivatives were designed, synthesized and evaluated. An in vitro study
      followed by in vivo and pharmacokinetic studies of these heterotricyclic
      compounds led us to the discovery of an orally active CRF1 receptor antagonist.
      The results of a structure-activity relationship study are presented.

PMID- 21865049
TI  - Cross-section measurements and nuclear model calculation for proton induced
      nuclear reaction on zirconium.
AB  - Proton induced nuclear reactions were measured with stacked-foil technique on
      natural zirconium targets up to 16.7MeV. Excitation functions were measured for
      the production of (90,92m,95m,95g,96)Nb and (88)Y. Cumulative cross-section,
      thick target yields and activation functions were deduced and compared with the
      available experimental data, as well as with the nuclear models codes; ALICE
      IPPE, EMPIRE and TALYS. The integral yields for thick targets were deduced from
      the measured excitation function of the produced radionuclides.

PMID- 21865048
TI  - 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4
      tetrahydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR
      12727): a potent, orally active dipeptidyl peptidase IV inhibitor without
      mechanism-based inactivation of CYP3A.
AB  - We report on the identification of 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]
      1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo[3,2-d]pyrimidine-5
      yl}methyl)-4-fluorobenzonitrile (DSR-12727) (7a) as a potent and orally active
      DPP-4 inhibitor without mechanism-based inactivation of CYP3A. Compound 7a showed
      good DPP-4 inhibitory activity (IC(50)=1.1 nM), excellent selectivity against
      related peptidases and other off-targets, good pharmacokinetic and
      pharmacodynamic profile, great in vivo efficacy in Zucker-fatty rat, and no
      safety concerns both in vitro and in vivo.

PMID- 21865050
TI  - Detection of explosive remnants of war by neutron thermalisation.
AB  - The HYDAD-D landmine detector (Brooks and Drosg, 2005) has been modified and
      field-tested for 17 months in a variety of soil conditions. Test objects
      containing about the same mass of hydrogen (20g) as small explosive remnants of
      war, such as antipersonnel landmines, were detected with efficiency 100% when
      buried at cover depths up to 10cm. The false alarm rate under the same conditions
      was 9%. Plots of detection efficiency versus false alarm rate are presented.

PMID- 21865051
TI  - Quality of Life in orthognathic surgery patients: post-surgical improvements in
      aesthetics and self-confidence.
AB  - The objective of this prospective study was to assess changes of Quality of Life
      (QoL) in patients undergoing bimaxillary orthognathic surgery. Questionnaires
      were based on the Oral Health Impact Profile (OHIP, items OH-1-OH-14) and three
      additional questions (items AD-1-3), and were completed by patients (n=50; mean
      age 26.9+/-9.9 years) on average 9.1+/-2.4 months before surgery, and 12.1+/-1.4
      months after surgery, using a scoring scale. Item scores describing functional
      limitation, physical pain, physical disability and chewing function did not
      change significantly, whereas item scores covering psychological discomfort and
      social disability domains revealed significant decreases following surgery. AD-2
      "dissatisfying aesthetics" revealed the greatest difference between pre- and post
      surgical scores (p<0.001). If there was a perception of aesthetic improvement of
      facial features post-surgery, the benefit in QoL was generally high. The
      significant correlation of the pre- to post-surgical changes of item OH-5 "self
      conscious" to nearly all other item changes suggested that OH-5 was the most
      sensitive indicator for post-surgical improvement of QoL. Psychological factors
      and aesthetics exerted a strong influence on the patients' QoL, and determined
      major changes more than functional aspects did.

PMID- 21865052
TI  - A new biomechanical model for evaluation of fixation systems of maxillofacial
      fractures.
AB  - The aim of this study was to develop a new type of biomechanical model for
      biomechanical researches of maxillofacial fractures and then evaluate it. Twenty
      synthetic polyurethane maxillary and mandibular models were used to simulate the
      mandible and maxilla. Springs were used to represent the forces of masseter,
      medial pterygoid, temporalis, and lateral pterygoid muscles acting on the models.
      Four masticatory conditions, namely clenching in the intercuspal position (ICP),
      incisal clenching (INC), left unilateral molar clenching (L-MOL, contralateral
      side of fracture) and right unilateral molar clenching (R-MOL, fracture side)
      were simulated. The strain on a miniplates placed across a simulated fracture was
      measured using strain gauges attached to the plate surface. During INC and L-MOL,
      the strain on the miniplates confirmed the findings of Champy. The upper
      miniplate was subjected to tension force and the lower miniplate to compression.
      When the bite point moved to the fracture, the tension-compression zone reversed,
      with the upper miniplate relatively compressed and the lower miniplate tension.
      During ICP, the tension-compression zone changed again, with both miniplates
      tension. In conclusion, we have successfully developed a model which is much
      closer to physiological conditions than models used previously. It is reliable
      and useful for biomechanical tests of mandibular fractures. Models including soft
      tissue need developing to further understand fracture healing biomechanics.

PMID- 21865053
TI  - Glandular odontogenic cyst: two high-risk cases treated with conservative
      approaches.
AB  - BACKGROUND: The glandular odontogenic cyst is a rare jawbone cyst that is
      considered to be an independent entity, although its histopathological
      characteristics may lead to an incorrect diagnosis as a low-grade mucoepidermoid
      carcinoma. The treatment of glandular odontogenic cysts is controversial. CASE
      REPORT: We present two high-risk cases treated with conservative approaches, one
      by enucleation and curettage and the other by marsupialisation. This report also
      presents a review of the clinical and pathological aspects of glandular
      odontogenic cysts, and considers their development. No evidence of disease was
      observed after 3 years of follow-up in the two cases presented. CONCLUSIONS: When
      possible, treatment plans for these lesions should be customised for each case,
      taking into account the data available in the literature and patient preferences.
      For high-risk cases, that are treated with conservative approaches, such as the
      two cases presented here, strict and regular controls and rigorous radiological
      follow-up evaluations are mandatory.

PMID- 21865054
TI  - Age- and gender-specific epistasis between ADA and TNF-alpha influences human
      life-expectancy.
AB  - Aging is a complex phenotype with multiple determinants but a strong genetic
      component significantly impacts on survival to extreme ages. The dysregulation of
      immune responses occurring with increasing age is believed to contribute to human
      morbidity and mortality. Conversely, some genetic determinants of successful
      aging might reside in those polymorphisms for the immune system genes regulating
      immune responses. Here we examined the main effects of single loci and multi
      locus interactions to test the hypothesis that the adenosine deaminase (ADA) and
      tumor necrosis factor alpha (TNF-alpha) genes may influence human life
      expectancy. ADA (22G>A, rs73598374) and TNF-alpha (-308G>A, rs1800629; -238G>A,
      rs361525) functional SNPs have been determined for 1071 unrelated healthy
      individuals from Central Italy (18-106 years old) divided into three gender
      specific age classes defined according to demographic information and accounting
      for the different survivals between sexes: for men (women), the first class
      consists of individuals<66 years old (<73 years old), the second class of
      individuals 66-88 years old (73-91 years old), and the third class of
      individuals>88 years old (>91 years old). Single-locus analysis showed that only
      ADA 22G>A is significantly associated with human life-expectancy in males
      (comparison 1 (age class 2 vs. age class 1), O.R. 1.943, P=0.036; comparison 2
      (age class 3 vs. age class 2), O.R. 0.320, P=0.0056). Age- and gender-specific
      patterns of epistasis between ADA and TNF-alpha were found using Generalized
      Multifactor Dimensionality Reduction (GMDR). In comparison 1, a significant two
      loci interaction occurs in females between ADA 22G>A and TNF-alpha -238G>A (Sign
      Test P=0.011). In comparison 2, both two-loci and three-loci interaction are
      significant associated with increased life-expectancy over 88 years in males. In
      conclusion, we report that a combination of functional SNPs within ADA and TNF
      alpha genes can influence life-expectancy in a gender-specific manner and that
      males and females follow different pathways to attain longevity.

PMID- 21865055
TI  - Surfactant protein A modulates the lipopolysaccharide-induced inflammatory
      response related to preterm birth.
AB  - Surfactant protein A (SP-A) functions in homeostasis of lung surfactant and in
      innate immunity. SP-A is secreted by the fetal lung into amniotic fluid.
      Additionally it has been detected in gestational tissues. We propose that SP-A
      influences intrauterine inflammation that is commonly associated with preterm
      birth, the main underlying cause of neonatal mortality and morbidity. We used our
      previously established mouse model of LPS-induced preterm birth of live-born pups
      to investigate the role of SP-A in preterm birth. Mice overexpressing rat SP-A
      (rSP-A) under the control of human SP-C promoter were used. Cytokine
      concentrations in maternal and fetal serum and in amniotic fluid and mRNA levels
      of several inflammatory mediators in lungs and in intrauterine tissues were
      quantified using Cytometric Bead Array and RNase Protection Assay, respectively.
      Higher levels of SP-A mRNA were observed in fetal lungs and intrauterine tissues
      of rSP-A mice compared with wild-type. Using Western blot we detected excess of
      SP-A protein in fetal lung and in amniotic fluid of rSP-A animals. Despite some
      differences in the basal levels of TNF-alpha and IL-10 between rSP-A and wild
      type animals, there were no differences in the duration of pregnancy. However,
      the levels of TNF-alpha, IL-10 and some other inflammatory mediators in
      intrauterine tissues and in amniotic fluid differed significantly between the
      mouse lines after maternal LPS given at 17dpc. We conclude that SP-A modulates
      the levels of intrauterine inflammatory mediators involved in preterm birth and
      may contribute to inflammatory processes related to spontaneous preterm labor.

PMID- 21865056
TI  - Comparison of labor and delivery care provided by certified nurse-midwives and
      physicians: a systematic review, 1990 to 2008.
AB  - BACKGROUND: Advanced practice nurses (APNs) in the United States could expand
      access to high-quality health care, particularly for underserved populations.
      Yet, there has been limited synthesis of the evidence related to their
      effectiveness as compared with other providers. The study reported here, part of
      a larger study that examined all four types of APNs, compares the labor and
      delivery care outcomes of certified nurse-midwives (CNMs) and physicians. DATA
      SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), and Proquest (for dissertations), were searched for the years 1990
      through 2008. STUDY ELIGIBILITY CRITERIA: Only those articles where processes or
      outcomes of care were quantitatively compared between CNMs and physicians were
      included. For all APNs, 27,993 citations were reviewed. For CNMs, 21 articles
      representing 18 unique studies reported either infant or maternal outcomes.
      METHODS: The systematic review followed established procedures (replicable search
      of relevant databases, sequential review to identify eligible studies,
      abstraction by two reviewers, assessment of quality, and grading of evidence).
      RESULTS: For measures that relate to the processes of care (e.g., epidural, labor
      induction, episiotomy), lower use was found for CNMs. For many of the infant
      outcomes (e.g., low Apgar, low birth weight, neonatal intensive care unit
      admission), there were no differences between physicians and CNMs. Perineal
      lacerations were lower and breastfeeding was higher among women cared for by CNMs
      compared with physicians. LIMITATIONS: The review addressed only CNMs practicing
      in the United States and outcomes measured during labor and delivery. The
      majority of study designs were observational and the models of care ranged from
      independent to shared, limiting the control for bias. Moreover, all reviewers
      were nurses. CONCLUSION: Differences in practice between CNMs and MDs seem to be
      well documented, particularly in the use of technology. Yet, the findings provide
      evidence that care by CNMs is safe and effective. CNMs should be better utilized
      to address the projected health care workforce shortages.

PMID- 21865057
TI  - Analysis of the center of pressure displacement, ground reaction force and
      muscular activity during step exercises.
AB  - Anterior Knee Pain (AKP) is considered as one of the most common, yet
      misunderstood, knee pathologies. The aim of this study was to evaluate the
      displacement area of the center of pressure, Ground Reaction Force (GRF), and the
      electromyography activity of the hip and the quadriceps muscles in healthy and
      AKP individuals during the step-up and step-down exercises. Both groups (Control
      group and AKP group) were composed of 15 volunteers submitted to the exercises on
      a force plate. The AKP group presented greater displacement area of the center of
      pressure for all the situations evaluated than the Control group (p<0.05), as
      well as a lesser magnitude of the GRF during the step-down exercise. The AKP
      group presented lower electromyography activity than the Control group in all
      situations evaluated. AKP individuals do not have muscle imbalances; they present
      a lower electromyography activity of the stabilizing muscles of the patella and
      hip and show greater instability in activities such as step up and down compared
      to normal subjects.

PMID- 21865058
TI  - Elevated cyclic stretch and serotonin result in altered aortic valve remodeling
      via a mechanosensitive 5-HT(2A) receptor-dependent pathway.
AB  - INTRODUCTION: Serotonin/5-hydroxytryptamine (5-HT) has been implicated in valve
      disease and in the modulation of valve mechanical properties. Several 5-HT
      receptor subtypes are also known to be mechanosensitive in other cell types, but
      this has not been studied in the context of the valve. In this study, we sought
      to understand the effects of elevated 5-HT levels and stretch overload on aortic
      valve remodeling and the dominant 5-HT receptor subtype that regulates these
      processes. METHODS AND RESULTS: Collagen biosynthesis and tissue mechanical
      properties of porcine aortic valve cusps were evaluated after 10% (physiologic)
      and 15% (pathologic) dynamic stretch. These studies were performed in normal
      medium or medium supplemented with 5-HT (1, 10, 100 MUM) in the absence and
      presence of 5-HT(2A) or 5-HT(2B) receptor antagonists. Fresh valves served as
      controls. Valve collagen content was maximal at the 10-MUM 5-HT concentration for
      both 10% and 15% stretch. The 5-HT(2A) receptor antagonist reduced collagen
      synthesis, cell proliferation, and hsp47 expression under elevated and normal
      stretch, whereas the 5-HT(2B) receptor antagonist was effective only at normal
      stretch. The pretransition stiffness of the valve cusps was also increased in
      response to 5-HT via a stretch-sensitive 5-HT(2A) mechanism, with the post
      transition stiffness unaltered. CONCLUSIONS: Combined elevated stretch and 5-HT
      resulted in increased valve collagen biosynthesis, cell proliferation, and tissue
      stiffness. These responses were inhibited by a 5-HT(2A) antagonist. This strongly
      suggests that the 5-HT(2A) receptor subtype is sensitive to elevated stretch.

PMID- 21865059
TI  - Deletion of discoidin domain receptor 2 does not affect smooth muscle cell
      adhesion, migration, or proliferation in response to type I collagen.
AB  - Collagen receptors expressed on vascular smooth muscle cells include the
      discoidin domain receptors (DDR1 and DDR2). DDR1 is known to play important roles
      in mediating smooth muscle cell responses to vascular injury, including
      neointimal hyperplasia, but much less is known about the function of DDR2. In
      this study, we harvested smooth muscle cells from DDR2 wild-type and knockout
      mice and studied the cells using in vitro models of migration and growth. There
      were no significant differences in the ability of Ddr2(+/+) or Ddr2(-/-) smooth
      muscle cells to attach to, migrate, or proliferate on type I collagen.
      Furthermore, neither matrix metalloproteinase (MMP) 2 nor MMP-9 activity nor type
      I collagen expression was different between the cell types. We conclude that in
      vitro, endogenous DDR2 is not required for smooth muscle cell hyperplastic
      responses to collagen.

PMID- 21865061
TI  - Course of size and density of metastatic renal cell carcinoma lesions in the
      early follow-up of molecular targeted therapy.
AB  - OBJECTIVE: Imaging-based monitoring of molecular therapies in oncology remains a
      challenge. Molecular therapies might have more pronounced effects on lesion
      density than on lesion size. We analyzed changes in lesion diameter and density
      in patients with metastasized renal cell cancer (mRCC) in the early follow-up of
      targeted therapy and compared size-based measurements according to Response
      Evaluation Criteria in Solid Tumors (RECIST) with size- and density-based
      response evaluations according to the Choi criteria. PATIENTS AND METHODS: A
      total of 22 patients treated with sorafenib (800 mg/d) were retrospectively
      analyzed. Relative changes (in %) in the greatest diameter and density of defined
      neoplastic "target lesions" were determined 8 weeks and 1 year after start of
      therapy in relation to a pretherapeutic baseline investigation. Data were
      analyzed according to RECIST (ver. 1.0), and results were compared with the
      response assessment based on Choi. Median survival was determined for all
      subgroups according to Choi or RECIST at the 8-week and 1-year follow-up.
      RESULTS: Applying RECIST, 18 patients (82%) demonstrated stable disease (SD) 8
      weeks after the start of targeted therapy, 3 patients (14%) partial response
      (PR), and 1 patient (4%) progressive disease (PD). Partial responders at 8 weeks
      had a median survival of 48 months. After 1 year, 59% of all patients still
      showed SD. Applying Choi, 15 patients (68%) showed PR 8 weeks after the start of
      therapy, 5 patients (23%) SD, and 2 patients (9%) PD. After 1 year, PR was still
      the predominant response group (64% of the patients). Partial responders after 8
      weeks had a median survival of 18 months. CONCLUSION: Choi defined more patients
      as partial responders at early stages of therapy than RECIST, but this was not an
      effective selection for patients with prolonged median survival. Evaluation of a
      larger patient cohort will further clarify the role of combined size- and density
      based follow-up strategies in targeted therapy of mRCC.

PMID- 21865062
TI  - Patterns and outcomes of aortofemoral bypass grafting in the era of endovascular
      interventions.
AB  - OBJECTIVES: The aim of the study is to study contemporary presentation patterns
      and clinical results in patients undergoing aortofemoral bypass (AFB) surgery.
      DESIGN: This was a retrospective comparative study. MATERIAL AND METHODS: During
      a 14-year period, 269 consecutive patients (mean age 65 years) underwent AFB.
      Indications included occlusive disease with severe intermittent claudication (IC)
      (n = 86), critical limb ischaemia (CLI, n = 97) and aneurysmo-occlusive disease
      (n = 86). RESULTS: From 2000-07 on, AFB was performed more frequently for
      occlusive disease with CLI than for other indications (48% vs. 31% before 2000, P
      = 0.009) and also in women (51% vs. 32% before 2000, P = 0.003), compared to the
      period before 2000. Thirty-day mortality was reduced during 2000-2007 to 2.4%,
      compared with 4.3% during 1993-1999, although this difference was not
      statistically significant (P = 0.73). Morbidity did not change substantially over
      the study period. Predictors of 30-day mortality included indication (CLI = 4.1%
      vs. claudication = 1.2% (P = 0.37)) and chronic kidney disease (CKD, serum
      creatinine > 1.5 mg dl-1) (11.1% vs. 2.9% in normal renal function, P = 0.07),
      the latter being the single predictor on multivariate analysis (hazard risk 4.2,
      P = 0.047). Overall 5 and 10-year assisted primary and secondary patency was 95%
      and 88%, and 99% and 95%, respectively. Survival at 5 and 10 years was 69% and
      48%, respectively. Patient age (hazard risk 1.05, P < 0.001), CKD (hazard risk
      1.79, P = 0.018) and diabetes (hazard risk 1.56, P = 0.022) were independent
      predictors of worse long-term survival. Long-term outcome did not change over the
      course of the study. CONCLUSIONS: In the contemporary era, AFB is more likely to
      be performed for CLI and in women than in the past. Despite these changes,
      perioperative mortality and morbidity remain low and long-term outcome excellent.

PMID- 21865060
TI  - Economic evaluations in shoulder pathologies: a systematic review of the
      literature.
AB  - BACKGROUND: Economic evaluations provide decision makers with a tool for reducing
      health care costs because they assess both the costs and consequences of health
      care interventions. This study reviewed the quality of published economic
      evaluations for shoulder pathologies. MATERIALS AND METHOD: A MEDLINE search was
      conducted to identify articles published from 1980 to 2010 that contained "cost"
      or "economic" combined with terms for several shoulder disorders and treatments.
      We selected studies that fit the definition of 1 of the 4 routinely performed
      economic evaluations: cost-minimization, cost-effectiveness, cost-utility, and
      cost-benefit analyses. Study quality was determined by measuring adherence to 6
      established health economic principles, as described in the literature. RESULTS:
      The search retrieved 942 studies. Of these, 32 were determined to be economic
      evaluations, and 53% of the economic evaluations were published from 2005 to
      2010. Only 8 of the 32 studies (25%) adhered to all 6 health economic principles.
      Publication in a nonsurgical journal (P < .05) or in more recent years (P < .01)
      was significantly associated with higher quality. CONCLUSION: Future health care
      resource allocation will likely be based on the economic feasibility of
      treatments. Although the number and quality of economic evaluations of shoulder
      disorders have risen in recent years, the current state of the literature is
      poor. Given that availability of such data may factor in private and public
      reimbursement decisions, there is a clear demand for more rigorous economic
      evaluations.

PMID- 21865063
TI  - Levels of growth differentiation factor-15 are high and correlate with clinical
      severity in transfusion-independent patients with beta thalassemia intermedia.
AB  - Transfusion-independent patients with beta thalassemia intermedia (TI) experience
      a variety of clinical complications attributed to the underlying ineffective
      erythropoiesis and subsequent anemia, hemolysis, and iron overload. Growth
      differentiation factor-15 (GDF-15) was recently investigated as a marker of
      ineffective erythropoiesis in several anemias. In this work, we evaluated GDF-15
      levels in 55 patients with TI. The mean GDF-15 level was 25,197.8+/-16,208.9pg/ml
      which is lower than values reported for patients with thalassemia major, yet
      considerably higher than those reported in patients with other congenital and
      acquired anemias. GDF-15 levels were significantly higher in splenectomized
      compared to non-splenectomized patients and correlated with anemia, markers of
      iron overload, and a pre-defined clinical severity score. Further studies are
      needed to determine the practical utility of GDF-15 measurement and its potential
      to reflect the severity of the clinical course in TI patients.

PMID- 21865064
TI  - It's complicated: pain, priorities and primary care.

PMID- 21865065
TI  - Evaluation of spin labels for in-cell EPR by analysis of nitroxide reduction in
      cell extract of Xenopus laevis oocytes.
AB  - Spin-label electron paramagnetic resonance (SL-EPR) spectroscopy has become a
      powerful and useful tool for studying structure and dynamics of
      biomacromolecules. However, utilizing these methods at physiological temperatures
      for in-cell studies is hampered by reduction of the nitroxide spin labels and
      thus short half-lives in the cellular environment. Consequently, reduction
      kinetics of two structurally different nitroxides was investigated in cell
      extracts of Xenopus laevis oocytes using rapid-scan cw-experiments at X-band. The
      five member heterocyclic ring nitroxide PCA (3-carboxy-2,2,5,5
      tetramethylpyrrolidinyl-1-oxy) under investigation features much higher stability
      against intracellular reduction than the six member ring analog TOAC (2,2,6,6
      tetramethylpiperidine-N-oxyl-4-amino-4-carboxilic acid) and is therefore a
      suitable spin label type for in-cell EPR. The kinetic data can be described
      according to the Michaelis-Menten model and thus suggest an enzymatic or enzyme
      mediated reduction process.

PMID- 21865066
TI  - Prediction of improvement in quality of life (QoL-AGHDA) in adults with growth
      hormone deficiency by normative reference limits: data of the German KIMS cohort.
AB  - OBJECTIVE: The objective of the present study was to calculate sex- and age
      specific normative values for health-related quality of life (HRQoL) in Germany
      using quantile regression. Furthermore, we investigate the estimates of these
      normative data to and to predict the improvement of QoL-AGHDA scores in the
      German KIMS cohort during growth hormone treatment. DESIGN: Normative data of
      HRQoL was assessed by quality of life assessment of growth hormone deficiency
      (GHD) in adults (QoL-AGHDA) in a representative sample of the German population
      (n=4172). Corresponding data for 888 patients with GHD were retrieved from the
      German KIMS cohort (Pfizer International Metabolic Database). RESULTS: The
      overall mean QoL-AGHDA score of the general population was 4.8+/-5.2. ANOVA
      indicated that variability in QoL-AGHDA scores did not differ significantly
      across gender (p=0.20), whereas age was a significant predictor (p<0.001). Given
      the QoL-AGHDA score distribution of the general population, we calculated
      reference values based on quantile regression. In KIMS patients we observed
      significantly higher QoL-AGHDA scores, 7.9+/-6.5 (p<0.001), before GH treatment.
      The optimal predictive QoL-AGHDA score was 6 (70th percentile) with a sensitivity
      of 0.57 and a specificity of 0.70 in ROC analysis. Furthermore, a baseline QoL
      AGHDA score above the 70th percentile allowed predicting an improvement of QoL by
      GH treatment. CONCLUSIONS: This study established normative reference values for
      the QoL-AGHDA in a representative sample of the German population. Based on these
      normative data a QoL-AGHDA cut-off value for prediction of improvement was
      investigated for the German population, which may facilitate clinical assessment
      of HRQoL response to GH replacement for patients with GHD.

PMID- 21865067
TI  - The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney
      disease.
AB  - OBJECTIVE: We have recently shown increased sensitivity to IGF-I induced signal
      transduction in kidneys of diabetic mice. Accordingly we investigated the effects
      of PQ401, a novel diarylurea compound that inhibits IGF1R autophosphorylation in
      type I diabetes. METHODS: Control (C) and Diabetic (D) mice were administered
      PQ401 (CP, DP) or vehicle (C, D) for 3weeks. RESULTS: CP animals showed a
      decrease in renal phosphorylated (p-)AKT and p-IGF1R. However, PQ401 had no
      effect on diabetic state (hyperglycemia, weight loss) or renal disease parameters
      (hypertrophy, hyperfiltration and albuminuria). Type IV collagen as well as TGF
      beta mRNA increased in DP and D compared to C. In the CP group renal hypertrophy
      with fat accumulation in proximal tubuli and increased renal IGF-I, collagen IV
      and TGF-beta mRNA were seen. CONCLUSIONS: IGF1R inhibition by PQ401 exerted no
      significant effects on diabetic kidney disease parameters, arguing against a role
      for IGF-I in the pathogenesis of diabetic kidney disease. However, PQ401 affects
      normal kidneys, inducing renal hypertrophy as well as collagen and fat
      accumulation, with increased renal IGF-I mRNA, suggestive of a damage
      regeneration process. Therefore, this diarylurea compound is not beneficial in
      early diabetic kidney disease. Its potential deleterious effects on kidney tissue
      need to be further investigated.

PMID- 21865068
TI  - PEGylation enhances the therapeutic potential for insulin-like growth factor I in
      central nervous system disorders.
AB  - OBJECTIVE: Due to its potent neurotrophic activity, insulin-like growth factor I
      (IGF-I) has been proposed many times for therapeutic application in disorders of
      the central nervous system (CNS). However, insufficient brain delivery to yield
      beneficial central without peripheral side effects have prevented clinical
      development in most instances. DESIGN: We recently reported the generation of a
      polyethylene-glycol modified IGF-I variant (PEG-IGF-I) with prolonged half-life
      and less acute side effects, but with fully maintained slow anabolic activity.
      Here we investigated if these beneficial properties result in improved brain
      availability of the drug, thereby reaching therapeutically relevant steady-state
      concentrations to elicit beneficial effects on neuronal function. RESULTS: After
      a single subcutaneous injection, PEG-IGF-I reached much higher steady-state
      levels in brain tissue and cerebrospinal fluid compared with IGF-I. Two weeks
      treatment with PEG-IGF-I was sufficient to modulate brain plasticity processes,
      as judged by changes in synaptic proteins and related animal behavior.
      Furthermore, chronic treatment of a mouse model of brain amyloidosis with PEG-IGF
      I reverted deficits in insulin/IGF-I signaling, synaptic proteins and cognitive
      performance. CONCLUSIONS: Our data generate the therapeutic potential for PEG-IGF
      I to treat CNS disorders by systemic drug application, and in addition
      scientifically support its application in disorders of synaptic function and
      neuronal development.

PMID- 21865069
TI  - Failure to increase postprandial blood flow in subcutaneous adipose tissue is
      associated with tissue resistance to adrenergic stimulation.
AB  - AIMS: Adequate adipose tissue blood flow (ATBF) is essential for its metabolic
      and endocrine functions. From a metabolic point of view, sufficient increases in
      ATBF after meals permits full storage of excess energy into fat, thus protecting
      other tissues against the toxic effects of fatty acids and glucose spillover. It
      was previously shown that postprandial increases in ATBF are blunted in obese and
      insulin-resistant subjects, and that much of the postprandial ATBF response is
      the result of beta-adrenergic activation. Examination of previously recorded data
      on postprandial ATBF responses revealed an underlying heterogeneity, with
      postprandial ATBF being largely unresponsive to food stimuli in a substantial
      proportion of normal weight healthy people (low responders). Our study tests the
      hypothesis that this unresponsive pattern is due to resistance to beta-adrenergic
      stimulation in adipose tissue. METHODS: Five responders and five low responders
      were selected from a previously studied cohort and matched for BMI (20.5+/-0.7 vs
      22+/-1 kg/m(2), respectively), gender (male/female: 2/3) and age (30+/-3 vs 37+/
      6 years). Subcutaneous adipose tissue microinfusions of stepwise increasing doses
      of isoproterenol were performed with concomitant monitoring of blood flow, using
      the (133)Xenon washout technique. RESULTS: Although BMI was similar between
      responders and low responders, there were significant differences in fat mass
      (9.9+/-1.6 vs 14.4+/-1.6 kg; P<0.05) and four-point skinfold thickness (33+/-4 vs
      52+/-16 mm; P<0.05). Lack of ATBF response to oral glucose was confirmed in the
      low responder group. In responders, ATBF was higher at baseline (5.4+/-1 vs 3.4+/
      1 mL/min/100 g of tissue) and responded more distinctly to increasing
      isoproterenol doses (10(-8) M: 7.6+/-1.4 vs 4.9+/-1; 10(-6) M: 12.5+/-1.7 vs
      7.5+/-1.6; and 10(-4) M: 20 +/-1.7 vs 9+/-0.9 mL/min/100 g of tissue).
      CONCLUSION: These data suggest that the lack of glucose-stimulated ATBF is
      associated with resistance to sympathetic activation in adipose tissue.

PMID- 21865070
TI  - [Anthropometric analysis of obstetrical pelvis from Neolithic area: obstetrical
      consequences. Preliminary study].
AB  - OBJECTIVES: To study female pelves from Neolithic area (5000 years AD) in order
      to better understand the evolution of obstetrical mecanisms. MATERIALS AND
      METHODS: The fossil material comprised 73 Homo sapiens pelves: we reconstructed
      all the 20 adult female bony pelves. We realised the shape and morphometric
      analysis of the pelvic cavity. Changes in pelvic neolithic morphology were
      compared with pelvic modern morphology. RESULTS: The pelves of prehistoric female
      were similar in shape with modern female. However, they differ in relative
      dimensions (transversal diameter of the pelvis inlet: respectively 118 mm vs 125
      mm, p=0.02). DISCUSSION AND CONCLUSION: Reconstructions based on Neolithic
      hominin fossils suggest that obstetrical mechanisms were probably common to
      Neolithic and modern humans: childbirth would probably require social adaptations
      and risks of perinatal and obstetric complications were undoubtedly high.
      However, the differences in morphometric analysis could suggest a change of human
      pelvis and raise the question of the evolution in obstetrical mechanisms in the
      future.

PMID- 21865071
TI  - Spinal cord stimulation for chronic pain improved motor function in a patient
      with Parkinson's disease.

PMID- 21865072
TI  - Injecting drug user views (and experiences) of drug-related litter bins in public
      places: a comparative study of qualitative research findings obtained from UK
      settings.
AB  - This paper provides a comparative study of qualitative research concerning drug
      related litter in community settings (associated with illicit drug use/rs) and of
      the modes of intervention (noted by municipal authorities in two different UK
      settings) aimed at reducing harm associated with this contemporary public health
      issue. More specifically, the paper focuses upon the views and experiences of 51
      injecting drug users regarding DRL-bin provision, service uptake and connected
      events in the relevant settings. Comparative analysis of these qualitative
      experiences appears to confirm Fitzpatrick and LaGory's concept of 'place
      matters' in any consideration of applied, low threshold, health intervention.
      Accordingly, street-based, drug-related intervention within public settings needs
      to be culturally, environmentally, spatially and geographically relevant to the
      intended target population in order to have any meaningful benefit (e.g. reduced
      opportunities for needlestick injury in community settings), impact (e.g.
      improved community safety) and related outcome (e.g. service uptake by injecting
      drug users).

PMID- 21865073
TI  - Mismatched perceptions of neighbourhood walkability: need for interventions?
AB  - Several studies have reported a mismatch between objectively measured
      characteristics of the obesogenic environment and perceptions of individuals of
      these characteristics. A recent study found a decline in walking and an increase
      in BMI in individuals living in high-walkable neighbourhoods, who perceived the
      walkability of these neighbourhoods as low, and recommends interventions aimed at
      improving this mismatch. We express our concern about the emphasis given to
      interventions based on misperceptions of the environment. It is argued that still
      little is understood about the underlying reasons for misperceptions, that bias
      needs to be ruled out, and that interventions aimed at improving mismatched
      perceptions may only be of little additional value.

PMID- 21865074
TI  - Exudate-based diabetic macular edema detection in fundus images using publicly
      available datasets.
AB  - Diabetic macular edema (DME) is a common vision threatening complication of
      diabetic retinopathy. In a large scale screening environment DME can be assessed
      by detecting exudates (a type of bright lesions) in fundus images. In this work,
      we introduce a new methodology for diagnosis of DME using a novel set of features
      based on colour, wavelet decomposition and automatic lesion segmentation. These
      features are employed to train a classifier able to automatically diagnose DME
      through the presence of exudation. We present a new publicly available dataset
      with ground-truth data containing 169 patients from various ethnic groups and
      levels of DME. This and other two publicly available datasets are employed to
      evaluate our algorithm. We are able to achieve diagnosis performance comparable
      to retina experts on the MESSIDOR (an independently labelled dataset with 1200
      images) with cross-dataset testing (e.g., the classifier was trained on an
      independent dataset and tested on MESSIDOR). Our algorithm obtained an AUC
      between 0.88 and 0.94 depending on the dataset/features used. Additionally, it
      does not need ground truth at lesion level to reject false positives and is
      computationally efficient, as it generates a diagnosis on an average of 4.4s
      (9.3s, considering the optic nerve localisation) per image on an 2.6 GHz platform
      with an unoptimised Matlab implementation.

PMID- 21865076
TI  - Functional genetic variants of TGF-beta1 and risk of tobacco-related oral
      carcinoma in high-risk Asian Indians.
AB  - Transforming growth factor (TGF)-beta1, the most abundant isoform of TGF-beta
      have been implicated in various stages of carcinogenesis such as epithelial to
      mesenchymal transition, enhanced expression of metalloproteases, down-regulation
      of cellular adhesion molecule, increased tumor motility and angiogenesis as well
      as local and systemic immunosuppression leading to a more aggressive and
      metastatic behavior. We assessed the association of TGF-beta1 functional genetic
      polymorphisms at codon 10 (869 T>C) and 25 (915 G>C) of exon 1 in 140 patients
      with tobacco-related oral squamous cell carcinoma (OSCC) and 120 normal subjects
      by PCR-RFLP. The frequency of 869 CC genotype and C allele were significantly
      higher in patients as compared to controls (P(c), 0.024 and 0.0004, respectively)
      while no significant difference was observed in the frequency of 915 CC genotype
      and C allele. In logistic regression analysis CC genotype (OR, 3.87; 95% CI, 1.78
      8.41) and C allele (OR, 2.20; 95% CI 1.51-3.20) appeared as susceptible while TT
      genotype and T allele as protective. In addition C(869)-C(915) haplotype with OR
      of 2.48 at 95% CI, 1.51-4.06 significantly (P=0.0003) increased the risk of
      tobacco-related OSCC in Asian Indians.

PMID- 21865075
TI  - Dynamic coupling between the motors of DNA replication: hexameric helicase, DNA
      polymerase, and primase.
AB  - Helicases are molecular motor proteins that couple NTP hydrolysis to directional
      movement along nucleic acids. A class of helicases characterized by their ring
      shaped hexameric structures translocate processively and unidirectionally along
      single-stranded (ss) DNA to separate the strands of double-stranded (ds) DNA,
      aiding both in the initiation and fork progression during DNA replication. These
      replicative ring-shaped helicases are found from virus to human. We review recent
      biochemical and structural studies that have expanded our understanding on how
      hexameric helicases use the NTPase reaction to translocate on ssDNA, unwind
      dsDNA, and how their physical and functional interactions with the DNA polymerase
      and primase enzymes coordinate replication of the two strands of dsDNA.

PMID- 21865077
TI  - A case report of bevacizumab-related osteonecrosis of the jaw: old problem, new
      culprit.

PMID- 21865078
TI  - Perineural invasion in oral squamous cell carcinoma: a discussion of significance
      and review of the literature.
AB  - Perineural invasion (PNI) is a tropism of tumor cells for nerve bundles in the
      surrounding stroma. It is a form of tumor spread exhibited by neurotropic
      malignancies that correlates with aggressive behavior, disease recurrence and
      increased morbidity and mortality. Oral squamous cell carcinoma (OSCC) is a
      neurotropic malignancy that traditionally has been difficult to treat and manage.
      Evidence suggests that demonstration of PNI in OSCC should impact adjuvant
      treatment decisions and surgical management of this disease. Despite its
      importance as a prognostic indicator, experimental studies to explore the
      molecular mechanisms responsible for PNI are limited. The aim of this review is
      to discuss the difficulties in evaluating for PNI, review the literature
      regarding the relationship of PNI with patient outcomes in OSCC, and summarize
      the recent studies describing the molecular agents associated with this
      pathological phenomenon.

PMID- 21865079
TI  - Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral
      squamous cell carcinoma.
AB  - The aberrant regulation of epigenetic systems including histone acetylation
      contributes to inappropriate gene expression in cancer cells. In this study, we
      investigated the antitumor effects of the novel histone deacetylase inhibitor (S)
      HDAC42 in oral squamous cell carcinoma (OSCC) cells. The antiproliferative effect
      of (S)-HDAC42 was multifold higher than that of suberoylanilide hydroxamic acid
      in a panel of oral squamous carcinoma cell lines examined. (S)-HDAC42 mediated
      caspase-dependent apoptosis by targeting multiple signaling pathways relevant to
      cell cycle progression and survival. We demonstrated that (S)-HDAC42
      downregulated the levels of phospho-Akt, cyclin D1, and cyclin-dependent kinase
      6, accompanied by increased p27 and p21 expression. In addition, (S)-HDAC42
      suppressed NF-kappaB signaling by blocking tumor necrosis factor-alpha-induced
      nuclear translocation, and activated reactive oxygen species generation. Finally,
      (S)-HDAC42 exhibited high potency in suppressing OSCC tumor growth in a Ca922
      xenograft nude mouse model. Together, these findings underscore the translational
      value of (S)-HDAC42 in fostering new therapeutic strategies for OSCC.

PMID- 21865080
TI  - The ins and outs of cellular Ca(2+) transport.
AB  - The cytoplasmic Ca(2+) signals that participate in nearly all aspects of plant
      growth and development encode information as binary switches or information-rich
      signatures. They are the result of influx (thermodynamically passive) and efflux
      (thermodynamically active) activities mediated by membrane transport proteins. On
      the influx side, confirming the molecular identities of Ca(2+)-permeable channels
      is still a major research topic. Cyclic nucleotide-gated channels and glutamate
      receptor-like channels are candidates well supported by evidence. On the efflux
      side, CAX antiporters and P-type ATPase pumps are the principal molecular
      entities. Both of these active transporters load Ca(2+) into specific
      compartments and have the potential to reduce the magnitude and duration of a
      Ca(2+) transient. Recent studies indicate calmodulin-activated Ca(2+) pumps in
      endomembrane systems can dampen the magnitude and duration of a Ca(2+) transient
      that could otherwise grow into a Ca(2+) cell death signature. An important
      challenge following molecular characterization of the influx and efflux pathways
      is to understand how they are coordinately regulated to produce a Ca(2+) switch
      or encode specific information into a Ca(2+) signature.

PMID- 21865081
TI  - Toward rational design of bacterial genomes.
AB  - The advent of genetic engineering-the ability to edit and insert DNA into living
      organisms-in the latter half of the 20th century created visions of a new era of
      synthetic biology, where novel biological functions could be designed and
      implemented for useful purposes. We are witnessing an exciting revolution of
      scale, wherein technical progresses allow for the manipulation of genetic
      material at the whole genome level. This will enable the manufacture of
      increasingly complex genetic designs to solve pressing challenges in health,
      energy and the environment-if and when such designs can be specified. We argue
      that the organized development of key common application organisms, engineered
      for engineerability, and attendant libraries of parts, pathways and standardized
      manufacturing are necessary for this genome-scale technology to realize its
      promise.

PMID- 21865082
TI  - Metabolite channeling and compartmentation in the human cell line AGE1.HN
      determined by 13C labeling experiments and 13C metabolic flux analysis.
AB  - This study focused on analyzing active pathways and the metabolic flux
      distribution in human neuronal AGE1.HN cells that is a desirable basis for a
      rational design and optimization of producing cell lines and production processes
      for biopharmaceuticals. (13)C-labeling experiments and (13)C metabolic flux
      analysis were conducted using glucose, glutamine, alanine and lactate tracers in
      parallel experiments. Connections between cytosolic and mitochondrial metabolite
      pools were verified, e.g., flux from TCA cycle metabolite (13)C to glycolytic
      metabolites. It was also found that lactate and alanine are produced from the
      same pyruvate pool and that consumed alanine is mainly directly metabolized and
      secreted as lactate. Activity of the pentose phosphate pathway was low being
      around 2.3% of the glucose uptake flux. This might be compensated in AGE1.HN by
      high mitochondrial malic enzyme flux producing NADPH. Mitochondrial pyruvate
      transport was almost zero. Instead pyruvate carbons were channeled via
      oxaloacetate into the TCA cycle which was mainly fed via alpha-ketoglutarate and
      oxaloacetate during the investigated phase. The data indicate that further
      optimization of this cell line should focus on the improved substrate usage which
      can be accomplished by an improved connectivity between glycolytic and
      mitochondrial pyruvate pools or by better control of the substrate uptake.

PMID- 21865083
TI  - Prevalence of snoring and associated factors in infancy.
AB  - INTRODUCTION: In children aged 3-12 years snoring is associated with significant
      neurocognitive and behavioural deficits; however, there are few studies that have
      considered both the prevalence of snoring in infants and associated factors that
      may influence the development of snoring. The goal of the present study was to
      examine sleep, snoring and associated factors in a community sample of 0-3 month
      olds. METHODS: Previously validated infant sleep and parent sleep questionnaires
      were completed by parents of 457 term infants aged 1-13.9 weeks old (mean age=4.6
      weeks; SD=2.7; 45% males) during a home-based nurse visit. RESULTS: Approximately
      9% of infants were reported to snore habitually (snoring >= 3 nights/week).
      Habitual snoring was significantly associated with exclusive formula feeding (OR:
      28.87; p<.01), maternal concern about child's breathing during sleep (OR: 3.91;
      p=.01) and restless sleep >= 3 nights/week (OR: 17.76; p<.001). CONCLUSION: These
      results show that snoring is as common in infants as it is in older children.
      Given the known relationships between Sleep Disordered Breathing (SDB) and
      neurocognitive development, the effect of SDB developing early in childhood may
      have important consequences on future developmental outcomes.

PMID- 21865084
TI  - Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18
      genotyping for cervical cancer screening of women aged 25 years and older: a
      subanalysis of the ATHENA study.
AB  - BACKGROUND: The ATHENA study was designed to assess the performance of
      carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping
      compared with liquid-based cytology for cervical cancer screening in a large US
      population aged 21 years and older. We did a subanalysis of this population to
      compare the screening performance of the cobas HPV test versus liquid-based
      cytology in women aged 25 years and older, and assess management strategies for
      HPV-positive women. METHODS: Women aged 25 years or older who were attending
      routine cervical screening were enrolled from 61 clinical centres in 23 US
      states. Cervical specimens were obtained for liquid-based cytology and HPV DNA
      testing with two first-generation assays (Amplicor HPV test and Linear Array HPV
      genotyping test) and the second-generation cobas HPV test (with individual HPV16
      and HPV18 detection). Colposcopy and diagnostic biopsies were done on women with
      atypical squamous cells of undetermined significance (ASC-US) or worse cytology,
      those who tested positive with either first-generation HPV test, and a random
      sample of women who tested negative for HPV and cytology. All women not selected
      for colposcopy received their results and exited the study. Participants and
      colposcopists were masked to cytology and HPV test results until the colposcopy
      visit was completed. The primary endpoint for this substudy was histologically
      confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or worse. This study
      is registered with ClinicalTrials.gov, number NCT00709891; the study is in the
      follow-up phase, which is due to be completed in December, 2012. FINDINGS: From
      May 27, 2008, to Aug 27, 2009, 47,208 women were enrolled, of whom 41,955 met our
      eligibility criteria. Valid cobas HPV and liquid-based cytology test results were
      available for 40,901 women (97%), who were included in this analysis. Of these,
      4275 women (10%) tested cobas HPV positive and 2617 (6%) had abnormal cytology.
      431 women were diagnosed with CIN2 or worse and 274 with CIN3 or worse. In women
      who had colposcopy, the cobas HPV test was more sensitive than liquid-based
      cytology for detection of CIN3 or worse (252/274 [92.0%, 95% CI 88.1-94.6] vs
      146/274 [53.3%, 95% CI 47.4-59.1]; difference 38.7%, 95% CI 31.9-45.5; p<0.0001).
      Addition of liquid-based cytology to HPV testing increased sensitivity for CIN3
      or worse to 96.7% (265/274, 95% CI 93.9-98.3), but increased the number of screen
      positives by 35.2% (5783/40,901 vs 4275/40,901) compared with HPV testing alone.
      As a triage test to identify CIN3 or worse in HPV-positive women, detection of
      HPV16, HPV18, or both alone was equivalent to detection of ASC-US or worse alone
      in terms of sensitivity (150/252 [59.5%] vs 133/252 [52.8%]; p=0.11) and positive
      predictive value (PPV) (150/966 [15.5%] vs 133/940 [14.1%]; p=0.20). Among HPV
      positive women, detection of HPV16, HPV18, or both or low-grade squamous
      intraepithelial lesion or worse cytology had better sensitivity (182/252 [72.2%];
      p<0.0001) and similar PPV (182/1314 [13.9%]; p=0.70) for detection of CIN3 or
      worse than ASC-US or worse cytology alone. Furthermore, detection of HPV16,
      HPV18, or both or high-grade squamous intraepithelial lesion or worse cytology
      had higher sensitivity (165/252 [65.5%]; p=0.0011) and PPV (165/1013 [16.3%];
      p=0.031) for detection of CIN3 or worse than ASC-US or worse cytology alone.
      INTERPRETATION: HPV testing with separate HPV16 and HPV18 detection could provide
      an alternative, more sensitive, and efficient strategy for cervical cancer
      screening than do methods based solely on cytology. FUNDING: Roche Molecular
      Systems.

PMID- 21865085
TI  - HPV16 and HPV18 genotyping in cervical cancer screening.

PMID- 21865086
TI  - Who should be targeted for vaccination against anal cancer?

PMID- 21865088
TI  - Commentary to 'analysis of indications for ureteral reimplantation in 3738
      children with vesicoureteral reflux: a single institutional cohort'.

PMID- 21865087
TI  - Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among
      young women: a nested analysis within the Costa Rica Vaccine Trial.
AB  - BACKGROUND: Anal cancer remains rare (incidence of about 1.5 per 100,000 women
      yearly), but rates are increasing in many countries. Human papillomavirus (HPV)
      16 and 18 infections cause most cases of anal cancer. We assessed efficacy of an
      AS04-adjuvanted HPV 16 and HPV 18 vaccine against anal infection with HPV 16, HPV
      18, or both (HPV 16/18). METHODS: Women from Costa Rica were registered between
      June 28, 2004, and Dec 21, 2005, in a randomised double-blind controlled trial
      that was designed to assess vaccine efficacy against persistent cervical HPV
      16/18 infections and associated precancerous lesions. Eligible women were
      residents of Guanacaste and selected areas of Puntarenas, Costa Rica, age 18-25
      years, in good general health, willing to provide informed consent, and were not
      pregnant or breastfeeding. Participants were randomly assigned (1:1) to receive
      an HPV vaccine (Cervarix, GlaxoSmithKline, Rixensart, Belgium) or a control
      hepatitis A vaccine (modified preparation of Havrix, GlaxoSmithKline, Rixensart,
      Belgium). Vaccines were administered in three 0.5 mL doses at enrolment, 1 month,
      and 6 months. Women, selected at the final blinded study visit 4 years after
      vaccination, provided anal specimens for assessment of vaccine efficacy against
      anal HPV 16/18 infection. Prevalence of anal HPV 16/18 infections, reported as
      vaccine efficacy, was the primary endpoint of the study described here. Vaccine
      efficacy against cervical HPV 16/18 infection in the same women at the 4-year
      visit was used as a comparator. Analyses were done in a restricted cohort of
      women who were negative for both cervical HPV 16 and HPV 18 DNA and who were HPV
      16 and HPV 18 seronegative before enrolment (HPV naive), and also in the full
      cohort of women who provided an anal specimen. Investigators were masked to group
      assignment. This study is registered at ClinicalTrials.gov, number NCT00128661.
      FINDINGS: All women who attended the final blinded study visit and consented to
      anal specimen collection were included in the analysis (4210 of 6352 eligible
      women). In the full cohort, vaccine efficacy against prevalent HPV 16/18
      infection measured one-time, 4 years post vaccination was lower at the anus
      (62.0%, 95% CI 47.1-73.1) compared with the cervix (76.4%, 67.0-83.5; p for
      interaction by anatomical site 0.031). In the restricted cohort, vaccine efficacy
      against anal HPV 16/18 infection was 83.6% (66.7-92.8), which was similar to
      vaccine efficacy against cervical HPV 16/18 infection (87.9%, 77.4-94.0). Safety
      issues were not addressed in the current analysis. Additional safety data will be
      published later in a separate article. INTERPRETATION: The AS04-adjuvanted
      vaccine affords strong protection against anal HPV infection, particularly among
      women more likely to be HPV naive at enrolment. FUNDING: National Cancer
      Institute with contributions from the National Institutes of Health Office of
      Research on Women's Health. Vaccine was provided by GlaxoSmithKline Biologicals.

PMID- 21865091
TI  - Pathology of uterine leiomyosarcomas and smooth muscle tumours of uncertain
      malignant potential.
AB  - Uterine leiomyosarcomas are the most common uterine sarcomas. For clinicians,
      they are difficult tumours to manage. Preoperative detection is difficult because
      of the similarity in clinical presentation to ordinary fibroids. They are highly
      aggressive tumours and the effectiveness of adjuvant therapy remains
      controversial with surgery remaining the mainstay of treatment. Despite
      treatment, disease frequently recurs. For pathologists, diagnosis of most
      leiomyosarcomas using current diagnostic criteria is usually straightforward, as
      most tumours often possess two or more diagnostic microscopic features, including
      diffuse atypia, high mitotic count and tumour cell necrosis. Diagnostic
      difficulties usually relate to tumours having only one of these worrisome
      features, with or without other additional unusual morphologic findings. These
      latter tumours have been labelled as uterine smooth-muscle tumours of uncertain
      malignant potential. Those that are followed by a recurrence are biologically low
      grade leiomyosarcomas. Epithelioid and myxoid leiomyosarcomas are less common,
      and their diagnostic criteria are different to tumours of usual spindle cell
      differentiation. In this review, we discuss the pathology of leiomyosarcomas,
      including an update on smooth-muscle tumours of uncertain malignant potential,
      with emphasis on the controversy of labelling of atypical leiomyomas. The
      problems with histologic diagnosis, immunohistochemical studies and molecular
      pathology are reviewed.

PMID- 21865089
TI  - HIV controllers: a multifactorial phenotype of spontaneous viral suppression.
AB  - A small minority of HIV-infected individuals, known as HIV controllers, is able
      to exert long-term control over HIV replication in the absence of treatment.
      Increasing evidence suggests that the adaptive immune system plays a critical
      role in this control but also that a combination of several host and/or viral
      factors, rather than a single cause, leads to this rare phenotype. Here, we
      review recent advances in the study of these remarkable individuals. We summarize
      the epidemiology and clinical characteristics of HIV controllers, and
      subsequently describe contributing roles of host genetic factors, innate and
      adaptive immune responses, and viral factors to this phenotype. We emphasize
      distinctive characteristics of HIV-specific CD4 T cell responses and of CD4 T
      cell subpopulations that are frequently found in HIV controllers. We discuss
      major controversies in the field and the relevance of the study of HIV
      controllers for the development of novel therapeutic strategies and vaccines.

PMID- 21865090
TI  - Therapeutic in vivo selection of thymic-derived natural T regulatory cells
      following non-myeloablative hematopoietic stem cell transplant for IPEX.
AB  - FOXP3 is critical for the development and function of CD4(+)CD25(bright) natural
      regulatory T cells (nTreg). Individuals harboring mutations in FOXP3 develop
      immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).
      We describe a child diagnosed with IPEX who underwent a reduced intensity, T and
      B cell depleted, matched unrelated donor bone marrow transplant followed by
      clinical resolution. Using lineage-specific donor chimerism studies, we
      demonstrate that non-myeloablative HSCT resolves disease in the context of low
      level donor hematopoietic stem cell (HSC) engraftment. Despite low-levels of
      donor HSC, thymically-derived nTreg and to a lesser extent CD4(+) and CD8(+) T
      cells, exhibit a selective in vivo growth advantage for populations containing a
      functional FOXP3 gene. Moreover, nTreg from this patient show regulatory function
      directly ex vivo. These results have implications for improving clinical therapy
      for patients with IPEX and provide mechanistic insight into the in vivo
      development of human nTreg and unexpectedly, non-regulatory T cells.

PMID- 21865092
TI  - Emotional intelligence and acute pain: the mediating effect of negative affect.
AB  - Emotional abilities are predictive variables of lower perceived pain. However, no
      studies have been published investigating the relationship between emotional
      intelligence (EI), which refers to the ability to accurately perceive, appraise,
      understand, communicate and regulate emotions, and pain. The objective of the
      present study was to analyze the influence of EI, measured using the Mayer
      Salovey-Caruso Emotional Intelligence Test (MSCEIT), on the level of sensory and
      affective pain generated by an experimental cold pressor task (CPT). In addition,
      we examined the influence of negative affect, as measured through the Positive
      and Negative Affect Schedule (PANAS), on the relationship between EI and pain.
      Healthy college students (N = 67) completed measures of EI before the CPT, during
      which they submerged their nondominant hand into ice water, and they completed
      measures of negative emotional state before and after the CPT. Participants with
      higher EI rated pain as less intense and perceived it as less unpleasant. Greater
      emotional intelligence predicted less pain in this experimental paradigm, and the
      effects seemed to be mediated by the lower NA reactivity associated with greater
      EI. PERSPECTIVE: Emotional intelligence is an important element in the processing
      of emotional information during an experience of acute pain since it reduces the
      level of negative affect generated by the experimental task.

PMID- 21865093
TI  - Impact of telephone medication therapy management on medication and health
      related problems, medication adherence, and Medicare Part D drug costs: a 6-month
      follow up.
AB  - BACKGROUND: The Medicare Modernization Act of 2003 mandated the provision of
      medication therapy management (MTM) to eligible Part D beneficiaries to improve
      medication-related outcomes. As MTM programs evolve, evaluation is necessary to
      help inform MTM best practices. OBJECTIVE: The objective of this study was to
      determine the impact of pharmacist-provided telephone MTM on: (1) medication and
      health-related problems (MHRPs); (2) medication adherence; and (3) Part D drug
      costs. METHODS: This quasi-experimental study included Part D beneficiaries from
      a Texas health plan. Andersen's Behavioral Model of Health Services Use served as
      the study framework. MTM utilization was the health behavior. Age, gender, and
      race were predisposing factors, and number of medications, chronic diseases, and
      medication regimen complexity were need factors. Outcomes were pre-to-post
      changes in: (1) MHRPs; (2) medication adherence, using the medication possession
      ratio (MPR); and (3) total drug costs. Multiple regression was used to analyze
      group differences while controlling for predisposing and need factors. RESULTS:
      At baseline, the intervention (n = 60) and control (n = 60) groups were not
      statistically different regarding predisposing and need factors, with the
      exception of gender. The intervention group had significantly (P = 0.009) more
      men compared with the control group (51.7% vs 28.3%). There were 4.8 (2.7) and
      9.2 (2.9) MHRPs identified at baseline and 2.5 (2.0) and 7.9 (3.0) MHRPs remained
      at the 6-month follow up in the intervention and control groups, respectively.
      The intervention group (vs control) had significantly more MHRPs resolved (P =
      0.0003). There were no significant predictors of change in MPR or total drug
      costs from baseline to follow up, although total drug costs decreased by $158 in
      the intervention group compared with a $118 increase in the control group.
      CONCLUSIONS: A telephone MTM program resolved significantly more MHRPs compared
      with a control group, but there were no significant changes in adherence and
      total drug costs.

PMID- 21865094
TI  - Serologic predictors of nonalcoholic steatohepatitis in a population undergoing
      bariatric surgery.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common in the morbidly obese.
      It is a condition that can lead to progressive fibrosis and cirrhosis. We
      determined the prevalence in a population undergoing bariatric surgery and
      evaluated the possible serologic predictors before the development of fibrosis.
      METHODS: Liver biopsies were taken from 370 consecutive patients who were
      undergoing laparoscopic bariatric surgery. The clinical and biochemical
      parameters were then assessed for correlation with the histologic features of
      nonalcoholic steatohepatitis. RESULTS: Of the 370 patients, 68 (18%) were found
      to have NASH. Increased insulin resistance, alanine transaminase, and total
      bilirubin were independently associated with the presence of NASH. The presence
      of >= 2 of the 3 provided the best combination of sensitivity (.71) and
      specificity (.71) for predicting NASH. CONCLUSION: Increased insulin resistance,
      alanine transaminase, and total bilirubin are serologic predictors for the
      presence of NASH before the development of fibrosis.

PMID- 21865095
TI  - Laparoscopic Heller myotomy and gastric bypass for achalasia after vertical
      banded gastroplasty.

PMID- 21865096
TI  - Laparoscopic revision of gastrojejunostomy and vagotomy for intractable marginal
      ulcer after revised gastric bypass.

PMID- 21865097
TI  - Long-term follow-up in patients undergoing open gastric bypass as a revisional
      operation for previous failed restrictive procedures.
AB  - BACKGROUND: We have previously described our early experience with Roux-en-Y
      gastric bypass (RYGB) as a revisional procedure. The favorable results have
      stimulated us to continue using RYGB as our standard operating procedure after
      failed bariatric surgery. Our objective was to evaluate the perioperative risks,
      weight result, and abdominal symptoms 5 years after revisional RYGB surgery at a
      university hospital in Sweden. METHODS: We studied 121 patients undergoing
      revisional open RYGB (age 42.0 yr, body mass index 37.7 kg/m(2), 101 women) 5
      years after RYGB surgery. The patients underwent reoperation because of either
      intolerable side effects or inferior weight loss. The initial procedures were
      horizontal gastroplasty (n = 2), vertical banded gastroplasty (n = 34), gastric
      banding (n = 21), and silicone adjustable gastric banding (n = 64). The mean
      interval between the first surgery and revision was 5 years. The 5-year follow-up
      data were obtained annually using a questionnaire survey. RESULTS: The average
      operating time was 162 minutes (range 75-355). In these 121 cases, 10 (8%)
      reoperations were performed in the first 30-day period (4 for leakage). No
      perioperative mortality occurred, and the 5-year follow-up rate was 91%. The mean
      body mass index was 30.7 kg/m(2). Seven patients (5.7%) had undergone subsequent
      surgery because of complications. At follow-up, 93% reported being very satisfied
      or satisfied with the revisional procedure. Disturbing abdominal symptoms after
      RYGB were rare. CONCLUSION: The perioperative risks of revisional RYGB are
      greater than those for primary RYGB. However, because the long-term weight
      results and patient satisfaction are very good, we believe that the 8%
      reoperative rate is acceptable. We consider RYGB to be a suitable procedure for
      patients in whom previous bariatric procedures have failed.

PMID- 21865099
TI  - Staphylococcus aureus and cystic fibrosis.

PMID- 21865098
TI  - CGK733 does not inhibit ATM or ATR kinase activity in H460 human lung cancer
      cells.

PMID- 21865101
TI  - Inflammatory response in acute chorioamnionitis.
AB  - Acute chorioamnionitis is the principal antecedent of premature birth and an
      important contributor to specific neonatal and other complications that may
      extend throughout subsequent life. A large number of studies have addressed
      surrogate markers of in-utero inflammation including cytokines, chemokines,
      pathogen-associated molecular patterns, and elicited host proteins. However,
      chorioamnionitis means inflammation occurring within the chorioamnion and the
      only practical direct measure available to assess this finding in most placentas
      is histopathology. The maternal and fetal inflammatory response to the presence
      of organisms within the placental membranes, so-called histologic
      chorioamnionitis, is the focus of this review. The issues addressed are the
      nature and origin of the eliciting antigen, mode of spread to the placenta,
      general characteristics of placental immunity, and a specific characterization of
      the spectrum of pathologic lesions observed in placentas with membrane infection.

PMID- 21865100
TI  - Neonatal renal vein thrombosis.
AB  - Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for
      pediatric hematologists and nephrologists. The precise mechanism for the onset
      and propagation of renal thrombosis within the neonatal population is unclear,
      but there is suggestion that acquired and/or inherited thrombophilia traits may
      increase the risk for renal thromboembolic disease during the newborn period.
      This review summarizes the most recent studies of neonatal RVT, examining its
      most common features, the prevalence of acquired and inherited prothrombotic risk
      factors among these patients, and evaluates their short and long term renal and
      thrombotic outcomes as they may relate to these risk factors. Although there is
      some consensus regarding the management of neonatal RVT, the most recent
      antithrombotic therapy guidelines for the management of childhood thrombosis do
      not provide a risk-based algorithm for the acute management of RVT among newborns
      with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition
      associated with a high mortality rate, it is associated with significant
      morbidity due to renal impairment. Recent evidence to evaluate the effects of
      heparin-based anticoagulation and thrombolytic therapy on the long term renal
      function of these patients has yielded conflicting results. Long term cohort
      studies and randomized trials may be helpful to clarify the impact of acute
      versus prolonged antithrombotic therapy for reducing the morbidity that is
      associated with neonatal RVT.

PMID- 21865102
TI  - Are we documenting chaperone use?

PMID- 21865103
TI  - The unwritten price of cosmetic tourism: an observational study and cost
      analysis.
AB  - INTRODUCTION AND AIMS: Cosmetic tourism, driven by the promise of inexpensive
      operations abroad, is increasingly popular despite warnings from professional
      bodies regarding associated risks. Increasing numbers of individuals have
      presented to our department requesting NHS treatment of complications from such
      surgery. We set out to characterize these patients and evaluate costs incurred
      through their assessment and management. MATERIAL AND METHODS: An observational
      study was conducted from 2007 to 2009 on patients presenting to a tertiary
      referral Plastic Surgery practice with complications of cosmetic tourism surgery.
      Demographic characteristics, as well as those related to the operation, were
      recorded. Hospital patient flow pathways were constructed, cost analysis
      performed using Patient Level Costing, and expenditure and profitability
      calculated. KEY RESULTS: Nineteen patients presented within the study period.
      Most operations were performed in Europe or Asia, and were primarily breast
      augmentation procedures (n=13). The principal complications were wound infection
      or dehiscence, and poor cosmetic results. Eleven patients received NHS treatment,
      at a cost of L120,841. The mean cost for all patients' management was L6360
      (range: L114-L57,968), rising to L10,878 for those accepted for treatment. For 8
      of the 9 patients (89%) for whom full patient level costing was available, the
      hospital incurred a financial loss. CONCLUSION: The costs to the NHS of managing
      complications of cosmetic tourism are substantial, and underestimated by central
      funding agencies.

PMID- 21865104
TI  - Prevention of gastrointestinal herniation into the chest following omental
      transposition by the use of ligamentum teres.

PMID- 21865105
TI  - Lipoma or liposarcoma? A cautionary case report.
AB  - MERRF syndrome (myoclonic epilepsy with ragged-red fibres) is a mitochondrial
      encephalomyopathy characterised by a mixed seizure disorder and myoclonus. The
      condition is associated with multiple large cervical lipomas that often require
      surgical excision. Comprehensive clinical examination combined with pre-operative
      radiographic imaging is vital in such cases to help differentiate benign fatty
      masses from potential liposarcomas. We describe a case in which a lipoma-like
      liposarcoma was identified following excision of what was expected, on clinical
      and radiological grounds, to be a lipoma. This case highlights the potential for
      sarcomatous changes in suspicious lipomas, and the key role that imaging plays in
      differentiating benign from malignant.

PMID- 21865106
TI  - Delayed breast implant reconstruction: a 10-year prospective study.
AB  - Studies of complications following reconstructive surgery with implants among
      women with breast cancer are needed. As the, to our knowledge, first prospective
      long-term study we evaluated the occurrence of complications following delayed
      breast reconstruction separately for one- and two-stage procedures. From the
      Danish Registry for Plastic Surgery of the Breast, which has prospectively
      registered data for women undergoing breast implantations since 1999, we
      identified 559 women without a history of radiation therapy undergoing 592
      delayed breast reconstructions following breast cancer during the period 1999 to
      2006; 239 one-stage procedures and 353 two-stage procedures. The postoperative
      course through November 2009 was evaluated by cumulative incidence adjusting for
      competing risks for the selected outcomes; hematoma, infection, seroma, implant
      rupture, severe capsular contracture (modified Baker III and IV), extrusion of
      the implant, asymmetry/displacement of the implant, any complication, and
      reoperation. These analyses were performed both overall and separately according
      to type of procedure (one- or two-stage). The overall 10-year risk estimates were
      68.1% for any complication, 7.7% for severe capsular contracture, 32.3% for
      displacement/asymmetry of the implant and 38.6% for reoperation. When comparing
      one- and two-stage procedures, we observed significantly higher risk estimates
      for infection, seroma and extrusion of the implant following two-stage
      procedures, whereas the risk of reoperation was significantly higher following
      the one-stage procedure. For both procedures, the majority of reoperations were
      due to asymmetry or displacement of the implant. In conclusion, non-radiated one-
      and two-stage delayed breast implant reconstructions are associated with
      substantial risks of complications and reoperation which should be taken into
      consideration in the planning of breast reconstruction.

PMID- 21865107
TI  - Report of the 2010 society of thoracic surgeons congenital heart surgery practice
      and manpower survey.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS) Workforce on Congenital Heart
      Surgery undertook a second subspecialty Practice and Manpower Survey (2005, 2010)
      to obtain contemporary data. METHODS: Preliminary research suggested a potential
      target group of 273 congenital heart surgeons, including 258 at 125 US centers
      and 15 at 8 Canadian centers. The web-based survey was sent to these surgeons,
      plus all individuals listing pediatric cardiac surgery on CTSNet. RESULTS: Two
      hundred forty-six responders included 213 active congenital heart surgeons, 16
      retired congenital heart surgeons, and 17 surgeons in training. Retirement age
      was 63.5+/-7.5 years. Two hundred thirteen active congenital heart surgeon
      responders represent 78% of the original estimate. Their responses generated the
      following data: The mean age was 49.2+/-8.5 (range, 35 to 75 years). American
      medical school graduates included 159 of 201 respondents (79%). Years of
      postgraduate training was 9.7+/-1.7. One hundred ninety-seven (92%) respondents
      were certified in thoracic surgery by the American Board of Thoracic Surgery
      (ABTS). Twenty-eight of 200 (14%) received their congenital heart surgery
      training outside the United States or Canada. One hundred forty-three of 190
      respondents (75%) perform exclusively congenital heart operations; 31 (16%)
      perform exclusively pediatric heart operations. Of 186 respondents, 54 (29%)
      perform fewer than 100 major congenital heart operations per year, 78 (42%)
      perform 100 to 199 procedures, and 54 (29%) perform 200 procedures or more.
      Active congenital heart surgeons have been in their current positions for 9.3+/
      8.6 years. Eight respondents are in their first year of practice. For 203
      respondents, mean anticipated years to retirement is 16.1+/-7.6. Twenty-eight
      anticipate retirement within 5 years; 31 in 6 to 10 years. CONCLUSIONS: These
      data should help facilitate rational plans to meet workforce needs for an
      expanding patient population.

PMID- 21865109
TI  - CT, MRI and PET imaging in peritoneal malignancy.
AB  - Imaging plays a vital role in the evaluation of patients with suspected or proven
      peritoneal malignancy. Nevertheless, despite significant advances in imaging
      technology and protocols, assessment of peritoneal pathology remains challenging.
      The combination of complex peritoneal anatomy, an extensive surface area that may
      host tumour deposits and the considerable overlap of imaging appearances of
      various peritoneal diseases often makes interpretation difficult. Contrast
      enhanced multidetector computed tomography (MDCT) remains the most versatile tool
      in the imaging of peritoneal malignancy. However, conventional and emerging
      magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT
      techniques offer significant advantages over MDCT in detection and surveillance.
      This article reviews established and new techniques in CT, MRI and PET imaging in
      both primary and secondary peritoneal malignancies and provides an overview of
      peritoneal anatomy, function and modes of disease dissemination with illustration
      of common sites and imaging features of peritoneal malignancy.

PMID- 21865110
TI  - [Novel conventional therapies in onco-hemathology].
AB  - Cytogenetic, molecular and phenotyping features of malignant hematologic diseases
      succeeded in improving their management by a more accurate stratification of
      patients according to several groups of risk and by providing a rational for
      targeted therapy. Three major types of treatment (excluding cellular therapy) are
      currently available in onco-hematology: conventional chemotherapy, small
      molecules for targeted therapy and monoclonal antibodies. Conventional
      chemotherapy with optimization of doses and multidrug-based regimens allowed to
      substantially improve survival of patients and keeps a place of choice in
      treatment of these diseases. Targeted treatments came from the cytogenetic and
      molecular characterization of hemopathies. Thus, the kinase Bcr-Abl, as a result
      of the translocation t(9;22)(q34;q11), has been successfully targeted by tyrosine
      kinase inhibitors (TKI) in chronic myeloid leukemia and Ph+ acute lymphoblastic
      leukemia. Molecular abnormalities like internal-tandem duplication/point
      activating mutations in FLT3 in some acute myeloblastic leukemia or epigenetic
      dysregulations in some blood malignancies can also be targeted by small
      molecules. Hematopoietic malignant cells are phenotypically characterized by
      expression of cluster of differentiation (CD) on their surface. These CD are
      detected by flow cytometry using specific antibodies. Monoclonal antibodies
      targeting different CD have been developed for treatment. Rituximab, an anti-CD20
      antibody, was the first monoclonal antibody successfully developed for treatment
      of malignant hematologic diseases. Since rituximab, many other monoclonal
      antibodies are being developed. Trends in malignant hematologic diseases
      presented here will include treatments, which have at least entered phase I/II
      clinical trials in adult or childhood leukemia. They include some novel drugs of
      conventional chemotherapy like second-generation nucleoside analogues. We will
      give an overview of the small molecules targeting the different cellular pathways
      and we will highlight those appearing as the most promising like novel TKIs. The
      large field of monoclonal antibodies will be also approached focusing on
      antibodies developed in leukemias.

PMID- 21865111
TI  - Microvessel density and VEGF expression seems to correlate with invasiveness of
      basal cell carcinoma.

PMID- 21865112
TI  - Expression pattern of VEGFR-1, -2, -3 and D2-40 protein in the skin of patients
      with systemic sclerosis.
AB  - The earliest clinical symptoms of systemic sclerosis (SSc) relate to disturbances
      in the peripheral vascular system. However, detailed examination of the
      microcirculation including the lymphatics in the skin of patients with SSc has
      not been reported. The aim of our study was to examine the expression patterns of
      vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3 and the
      lymphatic endothelial cell marker D2-40 in the skin of SSc patients. Skin biopsy
      specimens from nine patients with SSc were analysed by immunohistochemistry using
      antibodies against VEGFR-1, VEGFR-2, VEGFR-3 and D2-40 protein. The lumen area of
      lymphatic vessels was measured. The data were statistically analysed using the
      Mann-Whitney U test, Wilcoxon signed-ranks or Spearman's rank correlation
      coefficient method. The intensity of VEGFR-2 and VEGFR-3 staining in the skin of
      patients with SSc was significantly higher than that in healthy controls. The
      lumen area of lymphatic vessels in the skin of patients with SSc was
      significantly larger than that in healthy controls. This study details the
      expression of VEGFR and D2-40 in the skin of patients with SSc, and highlights a
      possible role of microcirculatory dysfunction in the pathogenesis of systemic
      sclerosis.

PMID- 21865113
TI  - Upper-ear eczema: an unusual case of allergic contact dermatitis due to rubber
      additives.

PMID- 21865114
TI  - Endothelial dysfunction in psoriasis patients: cross-sectional case-control
      study.
AB  - Psoriasis is an inflammatory, immunomediated skin disorder associated with an
      increased risk of cardiovascular disease. Psoriasis patients are at higher risk
      of atherothrombotic disease independently of the concomitance of traditional
      cardiovascular risk factors. Inflammation is one of the mechanisms involved in
      the development of endothelial dysfunction (ED), which is a marker of subclinical
      atherosclerosis. This study was designed to assess ED in psoriasis patients non
      invasively. Flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID)
      of the brachial artery were measured by ultrasonography in 32 psoriasis patients
      and 31 healthy controls. Diabetes mellitus, renal failure, a history of neoplasm,
      major cardiovascular and cerebrovascular disease and psoriatic arthritis were
      exclusion criteria. Psoriasis patients exhibited a significantly lower percent
      FMD compared with controls, but not a significantly different NID. Our data
      confirm that psoriasis is associated with impaired endothelial function and
      suggest that these patients suffer from subclinical atherosclerosis.

PMID- 21865115
TI  - Acne treatment with isotretinoin in a patient with Apert syndrome.

PMID- 21865116
TI  - In vitro activity of itraconazole in combination with terbinafine against
      clinical strains of itraconazole-insensitive Sporothrix schenckii.
AB  - Four strains of Sporothrix schenckii were isolated from patients with cutaneous
      sporotrichosis who failed itraconazole (ITC) treatment. To investigate the
      susceptibility of these strains to ITC and terbinafine (TRB) alone and in
      combination in 2 growth phases in vitro, a checkerboard microdilution method was
      used in accordance with the recommendations of the Clinical Laboratory Standards
      Institute (CLSI) was used in our study. The drug interaction was evaluated by
      assessing the fractional inhibitory concentration index (FICI). The geometric
      means (GMs) of the minimum inhibitory concentrations (MICs) of 4 insensitive
      strains were obviously higher than those of the sensitive isolates used for
      comparison. The FICI analysis revealed that only 2 isolates (25%) were
      synergistic in yeast form. Our results indicate the failure of clinical
      treatments might be caused by the insensitivity to ITC of these strains.

PMID- 21865118
TI  - Residents'corner July 2011.

PMID- 21865117
TI  - Lichen planus with palmoplantar involvement: rapid therapeutic response to
      acitretin.

PMID- 21865120
TI  - Residents'corner July 2011.

PMID- 21865121
TI  - Differentiation between basal cell carcinoma and trichoepithelioma by
      immunohistochemical staining of the androgen receptor: an overview.
AB  - Clinical and histopathological differentiation between basal cell carcinoma (BCC)
      and trichoepithelioma (TE) is a frequent problem. Attempts have been made to
      identify immunohistochemical markers helpful in differentiating them. A correct
      diagnosis is important because the tumours are treated differently. Recent
      studies showed the absence of androgen receptor (AR) expression in benign hair
      follicle tumours like TE. This study examines whether AR immunostaining is a
      useful diagnostic test to differentiate between BCC and TE. We randomly selected
      75 cases with histological diagnoses of either BCC (subtypes: superficial,
      nodular or infiltrative) or TE (subtypes: classic or desmoplastic) from the
      database of the pathology department of Maastricht University Medical Centre. The
      available haematoxylin & eosin (H&E) slides were reviewed by three independent
      investigators using predetermined characteristics. Fifty-six slides (38 BCC and
      18 TE) with unequivocal histological characteristics of either tumour were used
      for immunohistochemistry with AR antibodies. Any nuclear expression within the
      tumour was considered positive. AR expression was present in 5/8 classic TE, 0/10
      desmoplastic TE, 22/23 superficial or nodular BCC and in 10/15 infiltrative BCC.
      Immunohistochemical stain for AR is useful to differentiate between TE and BCC;
      particularly in desmoplastic TE versus infiltrative BCC (specificity and positive
      predictive value of 100%).

PMID- 21865122
TI  - Localisation value of ictal arterial spin-labelled sequences in partial seizures.
AB  - Perfusion-based magnetic resonance imaging (MRI) using pulsed arterial spin
      labelled (ASL) sequences is becoming a more commonly used tool for the diagnosis
      of patients with focal epilepsy. We report a patient with post-traumatic epilepsy
      and cortical haemorrhage who had a complex partial seizure characterised mainly
      by ictal speech (verbalisation) during MRI acquisition. Ictal ASL showed focal
      hyperperfusion over the right temporal region which had resolved on follow-up
      MRI, two weeks later. Seizure semiology and interictal EEG suggested seizure
      origin in the non-dominant temporal lobe, which matched the increased ictal blood
      flow observed by ASL. The patient had language dominance in the left hemisphere,
      as observed by functional MRI. Our findings suggest that focal hyperperfusion, as
      observed by ASL, may have localising value in temporal epilepsies when performed
      in the ictal period.

PMID- 21865123
TI  - Fibrosarcoma arising from a burn scar.

PMID- 21865124
TI  - Angelman syndrome and pseudo-hypsarrhythmia: a diagnostic pitfall.
AB  - Angelman syndrome is a rare genetic disorder scarcely diagnosed before the age of
      two years. We report the case of an eight-month-old female presenting with severe
      hypotonia, myoclonus, suspected spasms and an electroencephalogram with
      hypsarrhythmic-like features. She was initially treated with vigabatrin which
      resulted in worsening of myoclonic jerks. Fluorometric in situ hybridization
      revealed a chromosomal deletion at region 15q11-13. We discuss the case and
      differential diagnosis with other conditions including West syndrome. [Published
      with video sequences].

PMID- 21865125
TI  - Fronto-polar epilepsy masquerading as juvenile myoclonic epilepsy.
AB  - A woman diagnosed with juvenile myoclonic epilepsy for over 30 years presented
      with stereotyped episodes of abnormal sensations in both arms. Continuous video
      EEG monitoring for 14 days and MRI brain revealed that the patient's
      somatosensory events with associated postictal aphasia, as well as her myoclonic
      and generalised tonic-clonic seizures, were likely due to a symptomatic left
      fronto-polar epilepsy. Our case emphasizes the need for clinicians to consider
      fronto-polar epilepsy as a potential cause of myoclonic seizures, particularly
      when associated with other semiologic features suggestive of frontal lobe
      epilepsy. [Published with video sequences].

PMID- 21865126
TI  - Epileptic seizure induced by fennel essential oil.
AB  - An epileptic seizure is reported in a 38-year-old woman, known to be an epileptic
      patient. Although she was under antiepileptic treatment and had well-controlled
      epilepsy, she developed a typical generalised tonic-clonic seizure and remained
      unconscious for 45 minutes following ingestion of a number of cakes containing an
      unknown quantity of fennel essential oil. Involuntary diarrhoea accompanied her
      epileptic seizure. This reported case recalls the fact that fennel essential oil
      can induce seizures and that this oil should probably be avoided by patients with
      epilepsy. Labelling of products with fennel essential oil should refer to the
      risk of seizures, particularly for patients with epilepsy. An awareness programme
      should involve all stakeholders affected by this issue.

PMID- 21865127
TI  - "Benign" myoclonic epilepsy of infancy as the initial presentation of glucose
      transporter-1 deficiency.
AB  - We report the case of a young boy carrying a de novo missense mutation
      (c.1199G>T; p.R400L) in the SLC2A1 gene who presented initially with benign
      myoclonic epilepsy of infancy. Eventually, he had a poor outcome with refractory
      generalised tonic-clonic, myoclonic and absence seizures, ataxia, significant
      mental impairment and slowing of head growth. He responded poorly to ketogenic
      diet. This case extends the phenotype of GLUT1-related syndromes and also sheds
      light on the genetic basis of myoclonic epilepsies of infancy suggesting that
      variable outcome may depend on genetic factors. [Published with video sequences].

PMID- 21865128
TI  - Dravet syndrome with an exceptionally good seizure outcome in two adolescents.
AB  - We present two children who exhibited the characteristics of Dravet syndrome
      during infancy and young childhood, with SCN1A mutation, but nevertheless
      achieved seizure freedom for at least four years during adolescence. These
      patients had no episodes of convulsive status epilepticus with a duration of more
      than 30 minutes and their overall favourable seizure outcome may be related to
      the prevention of convulsive status epilepticus.

PMID- 21865129
TI  - A case imitating Panayiotopoulos syndrome.
AB  - Panayiotopoulos syndrome is one of the most common childhood-specific epileptic
      disorders. It is characterized by autonomic symptoms; the most common being
      emesis. However, the presence of emetic symptoms may cause misdiagnosis, for
      example with some organic disorders which have similar autonomic features. On the
      other hand, since this syndrome has been recently well documented, the tendency
      for early recognition may lead to overdiagnosis. Here, we present a case which
      could be mistaken for Panayiotopoulos syndrome based on anamnesis, however, with
      the aid of ictal video-EEG monitoring, the patient was shown to present with a
      non-epileptic psychogenic seizure. This report is an example of careful
      evaluation in order to avoid over- or underdiagnosis of this benign disorder.
      [Published with video sequences].

PMID- 21865130
TI  - HER2 in gastric cancer: a biomarker with clinical impact, but not without
      translational challenges.

PMID- 21865131
TI  - Gastric tumours in hereditary cancer syndromes: clinical features, molecular
      biology and strategies for prevention.
AB  - Gastric cancer is the major cause of cancer-related deaths worldwide. The
      majority of them are classified as sporadic, whereas the remaining 10% exhibit
      familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the
      most important condition that leads to hereditary gastric cancer. However, other
      hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer,
      familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and
      hereditary breast and ovarian cancer, entail a higher risk compared to the
      general population for developing this kind of neoplasia. In this review, we
      describe briefly the most important aspects related to clinical features,
      molecular biology and strategies for prevention in hereditary gastric associated
      to different cancer syndromes.

PMID- 21865132
TI  - Mesenchymal niches of bone marrow in cancer.
AB  - Over the last decade, genetic and cell biology studies have indicated that tumour
      growth is not only determined by malignant cancer cells themselves, but also by
      the tumour microenvironment. Cells present in the tumour microenvironment include
      fibroblasts, vascular, smooth muscle, adipocytes, immune cells and mesenchymal
      stem cells (MSC). The nature of the relationship between MSC and tumour cells
      appears dual and whether MSC are pro- or anti-tumorigenic is a subject of
      controversial reports. This review is focused on the role of MSC and bone marrow
      (BM) niches in cancer.

PMID- 21865133
TI  - Approaches for the study of cancer: towards the integration of genomics,
      proteomics and metabolomics.
AB  - Recent technological advances, combined with the development of bioinformatic
      tools, allow us to better address biological questions combining -omic approaches
      (i.e., genomics, metabolomics and proteomics). This novel comprehensive
      perspective addresses the identification, characterisation and quantitation of
      the whole repertoire of genes, proteins and metabolites occurring in living
      organisms. Here we provide an overview of recent significant advances and
      technologies used in genomics, metabolomics and proteomics. We also underline the
      importance and limits of mass accuracy in mass spectrometry-based -omics and
      briefly describe emerging types of fragmentation used in mass spectrometry. The
      range of instruments and techniques used to address the study of each -omic
      approach, which provide vast amounts of information (usually termed "high
      throughput" technologies in the literature) is briefly discussed, including
      names, links and descriptions of the main databases, data repositories and
      resources used. Integration of multiple -omic results and procedures seems
      necessary. Therefore, an emerging challenge is the integration of the huge amount
      of data generated and the standardisation of the procedures and methods used.
      Functional data integration will lead to answers to unsolved questions,
      hopefully, applicable to clinical practice and management of patients.

PMID- 21865134
TI  - Multidisciplinary approach in stage III non-small-cell lung cancer: standard of
      care and open questions.
AB  - Lung cancer is the most frequent cause of cancer death worldwide and its global
      incidence has been steadily increasing during recent decades. A third of patients
      with newly diagnosed non-small-cell lung cancer (NSCLC) present with locally
      advanced disease. There is not a single widely accepted standard of care for
      these patients because of the wide spectrum of presentation of the disease.
      Although feasible and safe in experienced hands, evidence that surgical resection
      after induction treatment improves overall survival (OS) is lacking. For
      resectable or potentially resectable stage III, the findings of two phase III
      trials suggest that surgical resection should not be considered a standard of
      care but rather reserved for selected patients after critical multidisciplinary
      assessment, in whom surgery improves survival after downstaging if pneumonectomy
      can be avoided or in some T4N0-1 resectable tumours. For unresectable stage III
      NSCLC the standard of care is a combination of chemotherapy and radiotherapy. In
      those patients with good performance status and minimal weight loss, the
      concurrent approach has resulted in a statistically significant improvement in OS
      rates compared with a sequential approach in randomised clinical trials, although
      several questions remain unresolved.

PMID- 21865135
TI  - Consensus of the Spanish Society of Medical Oncology (SEOM) and Spanish Society
      of Pathology (SEAP) for HER2 testing in gastric carcinoma.
AB  - The identification of HER2 alterations in advanced gastric carcinomas is of
      critical importance in daily clinical practice as such neoplasms require specific
      treatment with trastuzumab. For these reasons, pathologists and oncologists with
      expertise in gastric carcinomas and HER2 testing from both organisations (SEAP
      and SEOM) have endeavoured to discuss and agree on national guidelines for HER2
      testing in gastric carcinomas. These guidelines are based on the experience of
      those who participated in the discussions and also on experience published
      internationally. These agreed guidelines give the minimum requirements that a
      pathological anatomy laboratory must fulfil in order to guarantee adequate HER2
      testing in daily practice. Any laboratories which do not meet the minimum
      standards set out in the guidelines must make every effort to achieve compliance.

PMID- 21865136
TI  - Comparative analysis of loss of heterozygosity and expression profile in normal
      tissue, DCIS and invasive breast cancer.
AB  - INTRODUCTION: Ductal carcinoma in situ (DCIS) is considered to be related to the
      development of invasive breast cancer. The aim of molecular biological research
      of preinvasive breast lesion characteristics and comparison with normal tissues
      and tissue of invasive tumours is to identify patients at high risk of developing
      invasive tumour on the basis of already established preinvasive lesions, and thus
      influence clinical decision-making. The aim of our study was to analyse several
      key molecules involved in different cellular pathways important for cancer
      development and progression in different types of breast tissue and to describe
      similarities and differences between premalignant and malignant lesions. MATERIAL
      AND METHODS: Genetic material isolated from both the tumour and healthy tissue
      was examined by loss of heterozygosity (LOH) analysis and real-time PCR using
      collagen 2A as a house-keeping gene. RESULTS: We analysed 65 samples of healthy
      mammary gland, 25 DCIS and 42 invasive ductal breast cancer samples. We analysed
      the LOH in three genes: BRCA1, BRCA2 and p53; and the gene expression of the VEGF
      gene and Bcl-2 gene. LOH in the BRCA1 gene was present in 44.74% of invasive
      samples and in 8.69% of DCIS (p=0.026); LOH in the BRCA2 gene in 45.0% of
      invasive samples and in 9.52% of DCIS (p=0.036); LOH in the p53 gene in 32.5% of
      invasive samples and in 31.82% of DCIS (p=0.97). No LOH was observed in normal
      tissue samples. VEGF was overexpressed in 14.3% of invasive cancers and in 12.0%
      of DCIS. Overexpression of Bcl-2 was observed in 11.9% of invasive cancers and in
      8.0% of DCIS. CONCLUSION: We have confirmed that some of the molecular
      characteristics of DCIS are identical to those of invasive carcinoma. This
      approach could lead to the identification of molecular markers as indicators for
      the potential development of DCIS into invasive carcinoma or identification of
      DCIS subgroups with latent invasion.

PMID- 21865137
TI  - Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with
      cancer-related neuropathic pain: better pain relief, sleep and physical health.
AB  - BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP)
      found that a 10-fold increase in pregabalin (PGB) use increased patients'
      satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB)
      treatment was carried out to assess if the use of more specific NP-targeting
      drugs, such as PGB, in combined therapy, in patients with cancer-related NP,
      provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB-
      vs. non- PGB-treated patients in a 2-month epidemiological, prospective,
      multicentre study to assess NP prevalence and management in cancer pain patients
      visiting radiotherapy oncologic units. Patients undertook the Brief Pain
      Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical
      Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey.
      RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated
      with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with
      treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use
      37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain
      intensity and total interference with activities and in MOS overall sleep
      problems index were significantly larger in the PGB group. CONCLUSIONS: The
      addition of more specific NP-targeting drugs to usual treatment, such as PGB, in
      NP cancer patients provides more satisfaction with treatment and better outcomes
      in terms of pain intensity, interference with activities and sleep than
      treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could
      allow for less use of benzodiazepines.

PMID- 21865138
TI  - APC and KRAS mutations in distal colorectal polyps are related to smoking habits
      in men: results of a cross-sectional study.
AB  - BACKGROUND: The purpose of this study was (a) to evaluate the association between
      cigarette smoking and the prevalence of distal colorectal polyps and
      adenocarcinoma and (b) to analyse genetic alterations representing different
      molecular pathways of the colorectal carcinogenesis. METHODS: A total of 623
      asymptomatic male (mean age: 53 years; 50-65) car factory workers were included.
      Information on smoking habits and other lifestyle factors were collected followed
      by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were
      determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP)
      and adenomatous polyps (AP)). Data were analysed using unconditional multiple
      logistic regression models. RESULTS: Smokers had a higher prevalence of AP (OR
      2.1; 95% CI 1.2-3.6; p<0.05) and HP (OR 5.4; 95% CI 2.6- 11.1; p<0.05). No
      differences in CRC were observed. There was a dose-response relationship with the
      number of cigarettes smoked. The risk of developing AP or HP decreased after
      smoking cessation, even among heavy smokers (>=20 packs/year). KRAS mutations
      were more prevalent among smokers AP (OR 5.6; 95% CI 1.6-20.4; p=0.007). There
      was a trend of positive association with APC mutations (OR 3.5; 95% CI 0.9-4.4;
      p=0.096). APC and KRAS mutations were found in 36% and 61% of the HP of smokers,
      but were absent in non-smokers (p=0.89 and 0.78, respectively). There were no
      differences in MSI between smokers and non-smokers. CONCLUSIONS: Cigarette
      smoking is associated with a higher risk of developing both HP and AP and a
      higher prevalence of mutations in APC and KRAS.

PMID- 21865139
TI  - Multimodal therapy for adult Wilms' tumour: an experience from one centre.
AB  - INTRODUCTION: Wilms' tumour (WT) is very rare in adults but very common in
      children. Treatment guidelines for adult patients with WT are still insufficient.
      Some study groups recommend that therapeutic protocols for adults with WT (AWT)
      should follow the guidelines that have been established for children. OBJECTIVE:
      To describe the clinical and pathological characteristics of AWT as well as the
      treatment protocols and outcomes for AWT at our treatment centre. MATERIAL AND
      METHODS: Seven patients (5 females and 2 males) were diagnosed with AWT in our
      hospital between 2002 and 2009. The tumours were staged and the patients were
      treated according to the paediatric regimen recommended by the National Wilms'
      Tumor Study Group. RESULTS: The median patient age at the time of diagnosis was
      29 years (range, 16-37 years). Flank pain was the most common clinical
      presentation. One patient was in Stage I of disease development, two were in
      Stage II, two were in Stage III and two were in Stage IV. Anaplasia was present
      in 3 patients with Stage III or Stage IV disease. All of the patients but one
      underwent nephrectomy and 2 incomplete surgeries were performed. Seven patients
      received 2-drug or 3-drug chemotherapy (dactinomycin and vincristine and/or
      doxorubicin). Two patients with Stage III disease also received radiation therapy
      (a total dose of 3600 or 3960 cGy). Complete remission was achieved in 4
      patients. Three patients (one with Stage III disease, 2 patients with Stage IV
      disease) died of their disease and those patients were all classified with an
      unfavourable histological type called anaplasia. With a median follow-up of 53.5
      months (range, 40-102 months), the 3-year and 5-year overall survival rates were
      57.1% (95% confidence interval, 20.4-93.8%). CONCLUSIONS: The results of this
      report suggest that histological anaplasia might be an adverse prognostic factor
      for AWT. Proper application of the diagnostic and therapeutic regimens
      established for children may improve the prognosis of adult patients with WT.

PMID- 21865140
TI  - Tumour and serum MGMT promoter methylation and protein expression in glioblastoma
      patients.
AB  - INTRODUCTION: Methylation of the promoter of the MGMT gene and MGMT protein
      expression are recognized as predictive markers for response to alkylating
      chemotherapy in glioblastoma (GB). MATERIAL AND METHODS: We have assessed MGMT
      methylation with the methylation-specific polymerase chain reaction (MSP) in
      tumor samples from 70 GB patients and in serum samples from 37 of these patients.
      We have also assessed MGMT protein expression by immunohistochemical (IHC)
      analysis in tissue samples from 63 of these patients. RESULTS: We found
      concordance between MGMT methylation status in tissue and serum (Cohen's Kappa =
      0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum
      showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation
      test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated
      in tissue attained longer progression-free and overall survival. In the
      multivariate analysis, serum MGMT promoter methylation emerged as an independent
      factor for longer progression-free and overall survival. CONCLUSION: Serum-based
      MGMT methylation analysis offers a promising alternative to tumor-based MGMT
      analysis in cases where tissue samples are unavailable.

PMID- 21865141
TI  - A dose-dense schedule of docetaxel followed by doxorubicin and cyclophosphamide
      as neoadjuvant treatment for breast cancer: results from a phase II study.
AB  - INTRODUCTION: The objective was to evaluate a dose-dense schedule of docetaxel
      followed by doxorubicin and cyclophosphamide (AC) as neoadjuvant treatment for
      patients with locally advanced breast cancer. PATIENTS AND METHODS: Ninety-nine
      patients were included and received 100 mg/m(2) of docetaxel every two weeks for
      four cycles followed by 60 mg/m(2) of doxorubicin and 600 mg/m(2) of
      cyclophosphamide every two weeks for four cycles. Primary prophylaxis with
      granulocyte colony-stimulating factor (G-CSF) was administered systematically to
      all patients. RESULTS: Efficacy and toxicity analyses were carried out on an
      intention-to-treat basis. After treatment, complete pathological response in the
      breast and lymph nodes was confirmed in 15 patients (15%, 95% confidence interval
      [CI]: 8.4-22.9). Clinical response rate was 74% (95% CI: 65-82), of which 19%
      were complete responses. Breast-conserving surgery could be performed in 41% of
      patients. The dose-dense schedule was generally well tolerated. The most
      important grade 3/4 toxicities per patient were cutaneous toxicity (12.1%) and
      hepatic dysfunction (9.1%) during docetaxel administration, and neutropenia
      (28.1%) and leucopenia (8.3%) with AC. CONCLUSION: A dose-dense schedule of
      docetaxel followed by AC as neoadjuvant treatment is an effective and safe
      treatment for locally advanced breast cancer. Primary prophylaxis with G-CSF, and
      possibly the change in the sequence of drug administration, appears to play a
      major role in avoiding the excessive toxicity of dose-dense schedules.

PMID- 21865142
TI  - Prognosis of patients with thyroid cancer who do not undergo surgical treatment:
      a SEER database analysis.
AB  - BACKGROUND: The treatment for thyroid cancer is surgical. However, some patients
      do not undergo operations because of comorbidities or other reasons. There is
      little information about the prognosis of these patients. The aim of the present
      study was to describe patients with well differentiated thyroid carcinoma who did
      not undergo surgical treatment and to identify differences in prognostic
      variables and survival compared with patients treated surgically. METHODS: We
      conducted a retrospective review of a prospective cohort collected by the
      National Cancer Institute obtained from the Surveillance, Epidemiology and End
      Results (SEER) Program. All patient files with a diagnosis of thyroid cancer were
      selected (38,493 cases). Finally, 12,416 cases were used for the analysis.
      Treatment was divided into surgical or nonsurgical groups. Five-year survival
      rates were estimated and classified by the SEER stage. RESULTS: Eighty-six
      patients did not receive surgical treatment. These patients were older, had more
      advanced tumours and their treatment was less associated with complementary
      radiotherapy. Five-year overall survival rates were 96.7% for surgical patients
      vs. 56.8% for nonsurgical patients (p<0.001). The overall survival in the
      nonsurgery group for localised tumours decreased 14.9%, for regional tumours
      decreased 49.9% and for distant tumours decreased 61.8%. DISCUSSION: The patients
      who did not undergo surgical treatment showed less than 5-year overall survival.
      The SEER database does not offer information about comorbidities that could
      explain these differences.

PMID- 21865143
TI  - The present and future of radiation oncology in Spain.

PMID- 21865145
TI  - [Use of Integra in a case of extensive upper extremity avulsion].
AB  - Authors performed successful skin replacement with Integra, a dermal regeneration
      template, on a patient with circumferential avulsion injury including the elbow
      region and the dorsum of the hand. The take rate of Integra was 97%, followed by
      a 98% take rate of the split thickness mesh graft used for final wound coverage.
      Treatment modality provided excellent aesthetic and functional results,
      underlining the role of Integra in cases of extensive traumatic skin and soft
      tissue deficit, such as the treatment of avulsion injury.

PMID- 21865144
TI  - [Predictors of efficacy, mucosal healing and dose intensification during the
      first year of adalimumab therapy in patients with luminal and fistulizing Crohn's
      disease. National data from Hungary].
AB  - Adalimumab is a fully human monoclonal antibody targeting tumor necrosis factor
      with proven efficacy in the treatment of Crohn's disease in clinical trials. The
      aim of the present study was to investigate the predictors of medium term
      clinical efficacy and mucosal healing during adalimumab therapy in patients with
      Crohn's disease in specialized centers approved for biological therapy in
      Hungary. METHODS: Data of 201 Crohn's disease patients were prospectively
      captured (male/female: 112/89, median age: 24 years, duration: 8 years). Previous
      infliximab therapy was given in 97 (48.3%) patients, concomitant steroids in
      41.3% and azathioprine in 69.2% (combined: 26.4%) of patients. RESULTS: Overall
      clinical response and remission rates at 24 and 52 weeks were 78% and 52%, and
      69.4% and 44.4%, respectively. Endoscopic improvement and healing was achieved in
      43.1% and 23.6%, respectively. In a logistic regression model, clinical efficacy
      and normalized C-reactive protein at week 12, need for combined immunosuppression
      at induction, shorter disease duration and smoking were identified as independent
      predictors for 12-month clinical outcome, while normalized C-reactive protein at
      week 12, clinical remission at week 24, frequency of previous relapses and
      smoking were associated to endoscopic improvement/healing. Dose intensification
      to weekly dosing was needed in 16.4%. Parallel azathioprine therapy and clinical
      remission at week 12 was inversely associated to dose escalation to weekly
      dosing. CONCLUSION: Clinical efficacy and normalized C-reactive protein at week
      12, need for combined immunosuppression, luminal disease and smoking are
      predictors for medium term clinical efficacy/mucosal healing during adalimumab
      therapy, while parallel azathioprine therapy may decrease the probability for
      dose escalation.

PMID- 21865146
TI  - [Myocardial infarction associated with oral contraceptive use, smoking and
      elevated cholesterol level in a young patient].
AB  - Oral hormonal contraceptives are the safest methods for young patients to avoid
      unwanted pregnancy. They are well accepted and have certain beneficial effects;
      however, physicians should pay attention to risk factors even when applied in
      young age. Obesity, dyslipidemia, smoking and oral contraceptive pills alone or
      in combination may lead to serious adverse events. Authors present a young woman
      who developed acute myocardial infarction in association with several
      unconsidered risk factors including the use of contraceptive pills.

PMID- 21865147
TI  - [The metabolic syndrome--clinical significance in 2011. Position statement of the
      Hungarian Diabetes Society, Metabolism Work Group].

PMID- 21865148
TI  - [Dr. Pal Rethy (Schlotterbeck)].

PMID- 21865149
TI  - [History of artificial modification (deformation) of the human body. IV.
      Modification of the ear, nose, lips, and other body parts].

PMID- 21865151
TI  - RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy.
AB  - RhoB, a member of the Rho subfamily of small GTPases, mediates diverse cellular
      functions, including cytoskeletal organization, cell transformation and vesicle
      trafficking. The thymus undergoes progressive decline in its structure and
      function after puberty. We found that RhoB was expressed in thymic medullary
      epithelium. To investigate a role of RhoB in the regulation of thymic epithelial
      organization or thymocyte development, we analyzed the thymi of RhoB-deficient
      mice. RhoB-deficient mice were found to display earlier thymic atrophy. RhoB
      deficiency showed significant reductions in thymus weight and cellularity,
      beginning as early as 5 weeks of age. The enhanced expression of TGF-beta
      receptor type II (TGFbetaRII) in thymic medullary epithelium was observed in RhoB
      null mice. In addition, the expression of fibronectin, which is shown to be
      regulated by TGF-beta signaling, was accordingly increased in the mutant thymic
      medulla. Since there is no age-related change of RhoB expression in the thymus,
      it is unlikely that RhoB in thymic epithelium directly contributes to age-related
      thymic involution. Nevertheless, our findings strongly support a physiological
      role of RhoB in regulation of thymus development and maintenance through the
      inhibition of TGF-beta signaling in thymic medullary epithelium.

PMID- 21865153
TI  - Toward a hermeneutical conception of medicine: a conversation with Charles
      Taylor.

PMID- 21865152
TI  - Phase II study of the combination of cetuximab and weekly paclitaxel in the first
      line treatment of patients with recurrent and/or metastatic squamous cell
      carcinoma of head and neck.
AB  - BACKGROUND: The efficacy and safety of a novel combination of weekly paclitaxel
      and the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab for
      the first-line treatment of recurrent and/or metastatic squamous cell carcinoma
      of the head and neck were investigated. PATIENTS AND METHODS: Patients received
      paclitaxel (80 mg/m(2)) and cetuximab (400/250 mg/m(2)), weekly, until disease
      progression or unacceptable toxicity. The primary end point was response rate.
      RESULTS: Among 46 patients enrolled, the overall response rate was 54% [95%
      confidence interval (CI) 39% to 69%], with 10 (22%) complete responses and a
      disease control rate of 80%. Median progression-free and overall survival times
      were 4.2 (95% CI 2.9-5.5 months) and 8.1 months (95% CI 6.6-9.6 months),
      respectively. Common grade 3/4 adverse events were acne-like rash (24%), asthenia
      (17%) and neutropenia (13%). Prior chemotherapy and the development of acne-like
      rash were associated with tumor response but not survival. No association between
      tumor EGFR expression or EGFR gene copy number and response or survival was
      found. CONCLUSION: The combination of cetuximab and weekly paclitaxel was active
      and well tolerated by these poor prognosis patients and may be an option for the
      treatment of medically unfit patients, particularly those for whom platinum is
      contraindicated.

PMID- 21865155
TI  - Reduced insulin-like growth factor-I serum levels in formerly obese women
      subjected to laparoscopic-adjustable gastric banding or diet-induced long-term
      caloric restriction.
AB  - Life-span extension in laboratory rodents induced by long-term caloric
      restriction correlates with decreased serum insulin-like growth factor-I (IGF-I)
      levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging
      and increases longevity in mutant mouse models. In the present study, we show
      that long-term caloric restriction achieved by two different interventions for 4
      years, either laparoscopic-adjustable gastric banding or reducing diet, leads to
      reduced IGF-I serum levels in formerly obese women relative to normal-weight
      women eating ad libitum. Moreover, we present evidence that the long-term caloric
      restriction interventions reduce fasting growth hormone serum levels. The present
      study indicates that the activity of the growth hormone/IGF-I axis is reduced in
      long-term calorically restricted formerly obese humans. Furthermore, our findings
      suggest that the duration and severity of the caloric restriction intervention
      are important for the outcome on the growth hormone/IGF-I axis in humans.

PMID- 21865154
TI  - Challenges to recruitment and retention of African Americans in the gene
      environment trial of response to dietary interventions (GET READI) for heart
      health.
AB  - In this paper, challenges to recruiting African Americans specifically for a
      dietary feeding trial are examined, learning experiences gained and suggestions
      to overcome these challenges in future trials are discussed. A total of 333
      individuals were randomized in the trial and 234 (167 sibling pairs and 67
      parents/siblings) completed the dietary intervention and required DNA blood
      sampling for genetic analysis. The trial used multiple strategies for
      recruitment. Hand distributed letters and flyers through mass distribution at
      various churches resulted in the largest number (n = 153, 46%) of African
      Americans in the trial. Word of mouth accounted for the second largest number (n
      = 120, 36%) and included prior study participants. These two recruitment sources
      represented 82% (n = 273) of the total number of individuals randomized in GET
      READI. The remaining 18% (n = 60) consisted of a combination of sources including
      printed message on check stubs, newspaper articles, radio and TV appearances,
      screening events and presentations. Though challenging, the recruitment efforts
      for GET READI produced a significant number of African American participants
      despite the inability to complete the trial as planned because of low recruitment
      yields. Nevertheless, the recruitment process produced substantial numbers that
      successfully completed all study requirements.

PMID- 21865156
TI  - Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein
      sorting pathway.
AB  - Biogenesis of the posterior pole is critical to directed cell migration and other
      polarity-dependent processes. We show here that proteins are targeted to the
      posterior pole on the basis of higher order oligomerization and plasma membrane
      binding, the same elements that target proteins to exosomes/microvesicles (EMVs),
      HIV, and other retrovirus particles. We also demonstrate that the polarization of
      the EMV protein-sorting pathway can occur in morphologically non-polarized cells,
      defines the site of uropod formation, is induced by increased expression of EMV
      cargo proteins, and is evolutionarily conserved between humans and the protozoan
      Dictyostelium discoideum. Based on these results, we propose a mechanism of
      posterior pole biogenesis in which elevated levels of EMV cargoes (i) polarize
      the EMV protein-sorting pathway, (ii) generate a nascent posterior pole, and
      (iii) prime cells for signal-induced biogenesis of a uropod. This model also
      offers a mechanistic explanation for the polarized budding of EMVs and
      retroviruses, including HIV.

PMID- 21865157
TI  - Translational regulation of acetylcholinesterase by the RNA-binding protein
      Pumilio-2 at the neuromuscular synapse.
AB  - Acetylcholinesterase (AChE) is highly expressed at sites of nerve-muscle contact
      where it is regulated at both the transcriptional and post-transcriptional
      levels. Our understanding of the molecular mechanisms underlying its regulation
      is incomplete, but they appear to involve both translational and post
      translational events as well. Here, we show that Pumilio-2 (PUM2), an RNA binding
      translational repressor, is highly localized at the neuromuscular junction where
      AChE mRNA concentrates. Immunoprecipitation of muscle cell extracts with a PUM2
      specific antibody precipitated AChE mRNA, suggesting that PUM2 binds to the AChE
      transcripts in a complex. Gel shift assays using a bacterially expressed PUM2 RNA
      binding domain showed specific binding using wild type AChE 3'-UTR RNA segment
      that was abrogated by mutation of the consensus recognition site. Transfecting
      skeletal muscle cells with shRNAs specific for PUM2 up-regulated AChE expression,
      whereas overexpression of PUM2 decreased AChE activity. We conclude that PUM2
      binds to AChE mRNA and regulates AChE expression translationally at the
      neuromuscular synapse. Finally, we found that PUM2 is regulated by the motor
      nerve suggesting a trans-synaptic mechanism for locally regulating translation of
      specific proteins involved in modulating synaptic transmission, analogous to CNS
      synapses.

PMID- 21865158
TI  - Vav protein guanine nucleotide exchange factor regulates CD36 protein-mediated
      macrophage foam cell formation via calcium and dynamin-dependent processes.
AB  - Atherosclerosis, a chronic inflammatory disease, results in part from the
      accumulation of modified lipoproteins in the arterial wall and formation of lipid
      laden macrophages, known as "foam cells." Recently, we reported that CD36, a
      scavenger receptor, contributes to activation of Vav-family guanine nucleotide
      exchange factors by oxidatively modified LDL in macrophages. We also discovered
      that CD36-dependent uptake of oxidized LDL (oxLDL) in vitro and foam cell
      formation in vitro and in vivo was significantly reduced in macrophages deficient
      of Vav proteins. The goal of the present study was to identify the mechanisms by
      which Vav proteins regulate CD36-dependent foam cell formation. We now show that
      a Vav-dynamin signaling axis plays a critical role in generating calcium signals
      in mouse macrophages exposed to CD36-specific oxidized phospholipid ligands.
      Chelation of intracellular Ca(2+) or inhibition of phospholipase C-gamma (PLC
      gamma) inhibited Vav activation (85 and 70%, respectively, compared with vehicle
      control) and reduced foam cell formation (approximately 75%). Knockdown of
      expression by siRNA or inhibition of GTPase activity of dynamin 2, a Vav
      interacting protein involved in endocytic vesicle fission, significantly blocked
      oxLDL uptake and inhibited foam cell formation. Immunofluorescence microscopy
      studies showed that Vav1 and dynamin 2 colocalized with internalized oxLDL in
      macrophages and that activation and mobilization of dynamin 2 by oxLDL was
      impaired in vav null cells. These studies identified previously unknown
      components of the CD36 signaling pathway, demonstrating that Vav proteins
      regulate oxLDL uptake and foam cell formation via calcium- and dynamin 2
      dependent processes and thus represent novel therapeutic targets for
      atherosclerosis.

PMID- 21865159
TI  - Solution structure of the soluble receptor for advanced glycation end products
      (sRAGE).
AB  - The receptor for advanced glycation end products (RAGE) is a multiligand cell
      surface receptor involved in various human diseases, as it binds to numerous
      molecules and proteins that modulate the activity of other proteins. Elucidating
      the three-dimensional structure of this receptor is therefore most important for
      understanding its function during activation and cellular signaling. The major
      alternative splice product of RAGE comprises its extracellular region that occurs
      as a soluble protein (sRAGE). Although the structures of sRAGE domains were
      available, their assembly into the functional full-length protein remained
      unknown. We observed that the protein has concentration-dependent oligomerization
      behavior, and this is also mediated by the presence of Ca(2+) ions. Moreover,
      using synchrotron small angle x-ray scattering, the solution structure of human
      sRAGE was determined in the monomeric and dimeric forms. The model for the
      monomer displays a J-like shape, whereas the dimer is formed through the
      association of the two N-terminal domains and has an elongated structure. These
      results provide insights into the assembly of the RAGE homodimer, which is
      essential for signal transduction, and the sRAGE:RAGE heterodimer that leads to
      blockage of the receptor signaling, paving the way for the design of therapeutic
      strategies for a large number of different pathologies.

PMID- 21865160
TI  - Structural and enzymatic characterization of the streptococcal ATP/diadenosine
      polyphosphate and phosphodiester hydrolase Spr1479/SapH.
AB  - Spr1479 from Streptococcus pneumoniae R6 is a 33-kDa hypothetical protein of
      unknown function. Here, we determined the crystal structures of its apo-form at
      1.90 A and complex forms with inorganic phosphate and AMP at 2.30 and 2.20 A,
      respectively. The core structure of Spr1479 adopts a four-layer
      alphabetabetaalpha-sandwich fold, with Fe(3+) and Mn(2+) coordinated at the
      binuclear center of the active site (similar to metallophosphoesterases).
      Enzymatic assays showed that, in addition to phosphodiesterase activity for bis(p
      nitrophenyl) phosphate, Spr1479 has hydrolase activity for diadenosine
      polyphosphate (Ap(n)A) and ATP. Residues that coordinate with the two metals are
      indispensable for both activities. By contrast, the streptococcus-specific
      residue Trp-67, which binds to phosphate in the two complex structures, is
      indispensable for the ATP/Ap(n)A hydrolase activity only. Moreover, the AMP
      binding pocket is conserved exclusively in all streptococci. Therefore, we named
      the protein SapH for streptococcal ATP/Ap(n)A and phosphodiester hydrolase.

PMID- 21865161
TI  - Placenta-specific expression of the interleukin-2 (IL-2) receptor beta subunit
      from an endogenous retroviral promoter.
AB  - The long terminal repeat (LTR) sequences of endogenous retroviruses and
      retroelements contain promoter elements and are known to form chimeric
      transcripts with nearby cellular genes. Here we show that an LTR of the THE1D
      retroelement family has been domesticated as an alternative promoter of human
      IL2RB, the gene encoding the beta subunit of the IL-2 receptor. The LTR promoter
      confers expression specifically in the placental trophoblast as opposed to its
      native transcription in the hematopoietic system. Rather than sequence-specific
      determinants, DNA methylation was found to regulate transcription initiation and
      splicing efficiency in a tissue-specific manner. Furthermore, we detected the
      cytoplasmic signaling domain of the IL-2Rbeta protein in the placenta, suggesting
      that IL-2Rbeta undergoes preferential proteolytic cleavage in this tissue. These
      findings implicate novel functions for this cytokine receptor subunit in the
      villous trophoblast and reveal an intriguing example of ancient LTR exaptation to
      drive tissue-specific gene expression.

PMID- 21865162
TI  - Transcriptional regulation of neural retina leucine zipper (Nrl), a photoreceptor
      cell fate determinant.
AB  - The transcription factor neural retina leucine zipper (Nrl) is a critical
      determinant of rod photoreceptor cell fate and a key regulator of rod
      differentiation. Nrl(-/-) rod precursors fail to turn on rod genes and instead
      differentiate as cones. Furthermore, NRL mutations in humans cause retinitis
      pigmentosa. Despite the developmental and clinical significance of this gene,
      little is known about the transcriptional regulation of Nrl itself. In this
      study, we sought to define the cis- and trans-acting factors responsible for
      initiation and maintenance of Nrl transcription in the mouse retina. Utilizing a
      quantitative mouse retinal explant electroporation assay, we discovered a
      phylogenetically conserved, 30-base pair region immediately upstream of the
      transcription start site that is required for Nrl promoter activity. This region
      contains binding sites for the retinal transcription factors CRX, OTX2, and
      RORbeta, and point mutations in these sites completely abolish promoter activity
      in living retinas. Gel-shift experiments show that CRX, OTX2, and RORbeta can
      bind to the critical region in vitro, whereas ChIP experiments demonstrate
      binding of CRX and OTX2 to the critical region in vivo. Thus, our results
      indicate that CRX, OTX2, and RORbeta directly regulate Nrl transcription by
      binding to critical sites within the Nrl promoter. We propose a model in which
      Nrl expression is primarily initiated by OTX2 and RORbeta and later maintained at
      high levels by CRX and RORbeta.

PMID- 21865163
TI  - Genetic and genomic analyses of RNA polymerase II-pausing factor in regulation of
      mammalian transcription and cell growth.
AB  - Many mammalian genes are occupied by paused RNA polymerase II (pol II) in the
      promoter-proximal region on both sides of the transcription start site. However,
      the impact of pol II pausing on gene expression and cell biology is not fully
      understood. In this study, we used a Cre-Lox system to conditionally knock out
      the b subunit of mouse negative elongation factor (Nelf-b), a key pol II-pausing
      factor, in mouse embryonic fibroblasts. We found that Nelf-b was associated with
      the promoter-proximal region of the majority of expressed genes, yet genetic
      ablation of Nelf-b only affected the steady-state mRNA levels of a small
      percentage of the Nelf-b-associated genes. Interestingly, Nelf-b deletion also
      increased levels of transcription start site upstream transcripts at multiple
      negative elongation factor-associated genes. The direct target genes of Nelf-b
      were highly enriched with those involved in the control of cell growth and cell
      death. Correspondingly, Nelf-b knock-out mouse embryonic fibroblasts exhibited
      slower progression from quiescence to proliferation, as well as in a cycling cell
      population. Furthermore, Nelf-b deletion also resulted in increased apoptosis.
      Thus, the genetic and genomic studies provide new physiological and molecular
      insight into Nelf-mediated pol II pausing.

PMID- 21865164
TI  - Regulated binding of importin-alpha to protein kinase Cdelta in response to
      apoptotic signals facilitates nuclear import.
AB  - PKCdelta translocates into the nucleus in response to apoptotic agents and
      functions as a potent cell death signal. Cytoplasmic retention of PKCdelta and
      its transport into the nucleus are essential for cell homeostasis, but how these
      processes are regulated is poorly understood. We show that PKCdelta resides in
      the cytoplasm in a conformation that precludes binding of importin-alpha. A
      structural model of PKCdelta in the inactive state suggests that the nuclear
      localization sequence (NLS) is prevented from binding to importin-alpha through
      intramolecular contacts between the C2 and catalytic domains. We have previously
      shown that PKCdelta is phosphorylated on specific tyrosine residues in response
      to apoptotic agents. Here, we show that phosphorylation of PKCdelta at Tyr-64 and
      Tyr-155 results in a conformational change that allows exposure of the NLS and
      binding of importin-alpha. In addition, Hsp90 binds to PKCdelta with similar
      kinetics as importin-alpha and is required for the interaction of importin-alpha
      with the NLS. Finally, we elucidate a role for a conserved PPxxP motif, which
      overlaps the NLS, in nuclear exclusion of PKCdelta. Mutagenesis of the conserved
      prolines to alanines enhanced importin-alpha binding to PKCdelta and induced its
      nuclear import in resting cells. Thus, the PPxxP motif is important for
      maintaining a conformation that facilitates cytosplasmic retention of PKCdelta.
      Taken together, this study establishes a novel mechanism that retains PKCdelta in
      the cytoplasm of resting cells and regulates its nuclear import in response to
      apoptotic stimuli.

PMID- 21865165
TI  - High cell surface death receptor expression determines type I versus type II
      signaling.
AB  - Previous studies have suggested that there are two signaling pathways leading
      from ligation of the Fas receptor to induction of apoptosis. Type I signaling
      involves Fas ligand-induced recruitment of large amounts of FADD (FAS-associated
      death domain protein) and procaspase 8, leading to direct activation of caspase
      3, whereas type II signaling involves Bid-mediated mitochondrial perturbation to
      amplify a more modest death receptor-initiated signal. The biochemical basis for
      this dichotomy has previously been unclear. Here we show that type I cells have a
      longer half-life for Fas message and express higher amounts of cell surface Fas,
      explaining the increased recruitment of FADD and subsequent signaling. Moreover,
      we demonstrate that cells with type II Fas signaling (Jurkat or HCT-15) can
      signal through a type I pathway upon forced receptor overexpression and that
      shRNA-mediated Fas down-regulation converts cells with type I signaling (A498) to
      type II signaling. Importantly, the same cells can exhibit type I signaling for
      Fas and type II signaling for TRAIL (TNF-alpha-related apoptosis-inducing
      ligand), indicating that the choice of signaling pathway is related to the
      specific receptor, not some other cellular feature. Additional experiments
      revealed that up-regulation of cell surface death receptor 5 levels by treatment
      with 7-ethyl-10-hydroxy-camptothecin converted TRAIL signaling in HCT116 cells
      from type II to type I. Collectively, these results suggest that the type I/type
      II dichotomy reflects differences in cell surface death receptor expression.

PMID- 21865166
TI  - Tyrosine phosphorylation of protein kinase D2 mediates ligand-inducible
      elimination of the Type 1 interferon receptor.
AB  - Type 1 interferons (including IFNalpha/beta) activate their cell surface receptor
      to induce the intracellular signal transduction pathways that play an important
      role in host defenses against infectious agents and tumors. The extent of
      cellular responses to IFNalpha is limited by several important mechanisms
      including the ligand-stimulated and specific serine phosphorylation-dependent
      degradation of the IFNAR1 chain of Type 1 IFN receptor. Previous studies revealed
      that acceleration of IFNAR1 degradation upon IFN stimulation requires activities
      of tyrosine kinase TYK2 and serine/threonine protein kinase D2 (PKD2), whose
      recruitment to IFNAR1 is also induced by the ligand. Here we report that
      activation of PKD2 by IFNalpha (but not its recruitment to the receptor) depends
      on TYK2 catalytic activity. PKD2 undergoes IFNalpha-inducible tyrosine
      phosphorylation on specific phospho-acceptor site (Tyr-438) within the plekstrin
      homology domain. Activated TYK2 is capable of facilitating this phosphorylation
      in vitro. Tyrosine phosphorylation of PKD2 is required for IFNalpha-stimulated
      activation of this kinase as well as for efficient serine phosphorylation and
      degradation of IFNAR1 and ensuing restriction of the extent of cellular responses
      to IFNalpha.

PMID- 21865167
TI  - Reactive oxygen species and p38 mitogen-activated protein kinase mediate tumor
      necrosis factor alpha-converting enzyme (TACE/ADAM-17) activation in primary
      human monocytes.
AB  - Tumor necrosis factor alpha-converting enzyme (TACE) is responsible for the
      shedding of cell surface TNF. Studies suggest that reactive oxygen species (ROS)
      mediate up-regulation of TACE activity by direct oxidization or modification of
      the protein. However, these investigations have been largely based upon
      nonphysiological stimulation of promonocytic cell lines which may respond and
      process TACE differently from primary cells. Furthermore, investigators have
      relied upon TACE substrate shedding as a surrogate for activity quantification.
      We addressed these concerns, employing a direct, cell-based fluorometric assay to
      investigate the regulation of TACE catalytic activity on freshly isolated primary
      human monocytes during LPS stimulation. We hypothesized that ROS mediate up
      regulation of TACE activity indirectly, by activation of intracellular signaling
      pathways. LPS up-regulated TACE activity rapidly (within 30 min) without changing
      cell surface TACE expression. Scavenging of ROS or inhibiting their production by
      flavoprotein oxidoreductases significantly attenuated LPS-induced TACE activity
      up-regulation. Exogenous ROS (H(2)O(2)) also up-regulated TACE activity with
      similar kinetics and magnitude as LPS. H(2)O(2)- and LPS-induced TACE activity up
      regulation were effectively abolished by a variety of selective p38 MAPK
      inhibitors. Activation of p38 was redox-sensitive as H(2)O(2) caused p38
      phosphorylation, and ROS scavenging significantly reduced LPS-induced phospho-p38
      expression. Inhibition of the p38 substrate, MAPK-activated protein kinase 2,
      completely attenuated TACE activity up-regulation, whereas inhibition of ERK had
      little effect. Lastly, inhibition of cell surface oxidoreductases prevented TACE
      activity up-regulation distal to p38 activation. In conclusion, our data indicate
      that in primary human monocytes, ROS mediate LPS-induced up-regulation of TACE
      activity indirectly through activation of the p38 signaling pathway.

PMID- 21865168
TI  - New N-acetyltransferase fold in the structure and mechanism of the phosphonate
      biosynthetic enzyme FrbF.
AB  - The enzyme FrbF from Streptomyces rubellomurinus has attracted significant
      attention due to its role in the biosynthesis of the antimalarial phosphonate FR
      900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR
      900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine
      5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established
      function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to
      any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we
      present the 2.0 A resolution crystal structure of FrbF in complex with acetyl
      CoA, which demonstrates a unique architecture that is distinct from those of
      canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure
      to guide structure-function studies that identified the roles of putative active
      site residues in the acetyltransferase mechanism. The combined biochemical and
      structural analyses of FrbF provide insights into this previously uncharacterized
      family of N-acetyltransferases and also provide a molecular framework toward the
      production of novel N-acyl derivatives of FR-900098.

PMID- 21865169
TI  - Characterization of the activities of the CpeY, CpeZ, and CpeS bilin lyases in
      phycoerythrin biosynthesis in Fremyella diplosiphon strain UTEX 481.
AB  - When grown in green light, Fremyella diplosiphon strain UTEX 481 produces the red
      colored protein phycoerythrin (PE) to maximize photosynthetic light harvesting.
      PE is composed of two subunits, CpeA and CpeB, which carry two and three
      phycoerythrobilin (PEB) chromophores, respectively, that are attached to specific
      Cys residues via thioether linkages. Specific bilin lyases are hypothesized to
      catalyze each PEB ligation. Using a heterologous, coexpression system in
      Escherichia coli, the PEB ligation activities of putative lyase subunits CpeY,
      CpeZ, and CpeS were tested on the CpeA and CpeB subunits from F. diplosiphon.
      Purified His(6)-tagged CpeA, obtained by coexpressing cpeA, cpeYZ, and the genes
      for PEB synthesis, had absorbance and fluorescence emission maxima at 566 and 574
      nm, respectively. CpeY alone, but not CpeZ, could ligate PEB to CpeA, but the
      yield of CpeA-PEB was lower than achieved with CpeY and CpeZ together. Studies
      with site-specific variants of CpeA(C82S and C139S), together with mass
      spectrometric analysis of trypsin-digested CpeA-PEB, revealed that CpeY/CpeZ
      attached PEB at Cys(82) of CpeA. The CpeS bilin lyase ligated PEB at both Cys(82)
      and Cys(139) of CpeA but very inefficiently; the yield of PEB ligated at Cys(82)
      was much lower than observed with CpeY or CpeY/CpeZ. However, CpeS efficiently
      attached PEB to Cys(80) of CpeB but neither CpeY, CpeZ, nor CpeY/CpeZ could
      ligate PEB to CpeB.

PMID- 21865170
TI  - The structure of sucrose synthase-1 from Arabidopsis thaliana and its functional
      implications.
AB  - Sucrose transport is the central system for the allocation of carbon resources in
      vascular plants. During growth and development, plants control carbon
      distribution by coordinating sites of sucrose synthesis and cleavage in different
      plant organs and different cellular locations. Sucrose synthase, which reversibly
      catalyzes sucrose synthesis and cleavage, provides a direct and reversible means
      to regulate sucrose flux. Depending on the metabolic environment, sucrose
      synthase alters its cellular location to participate in cellulose, callose, and
      starch biosynthesis through its interactions with membranes, organelles, and
      cytoskeletal actin. The x-ray crystal structure of sucrose synthase isoform 1
      from Arabidopsis thaliana (AtSus1) has been determined as a complex with UDP
      glucose and as a complex with UDP and fructose, at 2.8- and 2.85-A resolutions,
      respectively. The AtSus1 structure provides insights into sucrose catalysis and
      cleavage, as well as the regulation of sucrose synthase and its interactions with
      cellular targets.

PMID- 21865171
TI  - Clustering and internalization of toxic amylin oligomers in pancreatic cells
      require plasma membrane cholesterol.
AB  - Self-assembly of the human pancreatic hormone amylin into toxic oligomers and
      aggregates is linked to dysfunction of islet beta-cells and pathogenesis of type
      2 diabetes mellitus. Recent evidence suggests that cholesterol, an essential
      component of eukaryotic cells membranes, controls amylin aggregation on model
      membranes. However, the pathophysiological consequence of cholesterol-regulated
      amylin polymerization on membranes and biochemical mechanisms that protect beta
      cells from amylin toxicity are poorly understood. Here, we report that plasma
      membrane (PM) cholesterol plays a key role in molecular recognition, sorting, and
      internalization of toxic amylin oligomers but not monomers in pancreatic rat
      insulinoma and human islet cells. Depletion of PM cholesterol or the disruption
      of the cytoskeleton network inhibits internalization of amylin oligomers, which
      in turn enhances extracellular oligomer accumulation and potentiates amylin
      toxicity. Confocal microscopy reveals an increased nucleation of amylin oligomers
      across the plasma membrane in cholesterol-depleted cells, with a 2-fold increase
      in cell surface coverage and a 3-fold increase in their number on the PM.
      Biochemical studies confirm accumulation of amylin oligomers in the medium after
      depletion of PM cholesterol. Replenishment of PM cholesterol from intracellular
      cholesterol stores or by the addition of water-soluble cholesterol restores
      amylin oligomer clustering at the PM and internalization, which consequently
      diminishes cell surface coverage and toxicity of amylin oligomers. In contrast to
      oligomers, amylin monomers followed clathrin-dependent endocytosis, which is not
      sensitive to cholesterol depletion. Our studies identify an actin-mediated and
      cholesterol-dependent mechanism for selective uptake and clearance of amylin
      oligomers, impairment of which greatly potentiates amylin toxicity.

PMID- 21865172
TI  - Structural basis for the interaction of lipopolysaccharide with outer membrane
      protein H (OprH) from Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a major nosocomial pathogen that infects cystic
      fibrosis and immunocompromised patients. The impermeability of the P. aeruginosa
      outer membrane contributes substantially to the notorious antibiotic resistance
      of this human pathogen. This impermeability is partially imparted by the outer
      membrane protein H (OprH). Here we have solved the structure of OprH in a lipid
      environment by solution NMR. The structure reveals an eight-stranded beta-barrel
      protein with four extracellular loops of unequal size. Fast time-scale dynamics
      measurements show that the extracellular loops are disordered and unstructured.
      It was previously suggested that the function of OprH is to provide increased
      stability to the outer membranes of P. aeruginosa by directly interacting with
      lipopolysaccharide (LPS) molecules. Using in vivo and in vitro biochemical
      assays, we show that OprH indeed interacts with LPS in P. aeruginosa outer
      membranes. Based upon NMR chemical shift perturbations observed upon the addition
      of LPS to OprH in lipid micelles, we conclude that the interaction is
      predominantly electrostatic and localized to charged regions near both rims of
      the barrel, but also through two conspicuous tyrosines in the middle of the
      bilayer. These results provide the first molecular structure of OprH and offer
      evidence for multiple interactions between OprH and LPS that likely contribute to
      the antibiotic resistance of P. aeruginosa.

PMID- 21865173
TI  - Cohen syndrome-associated protein, COH1, is a novel, giant Golgi matrix protein
      required for Golgi integrity.
AB  - Loss-of-function mutations in the gene COH1, also known as VPS13B, lead to
      autosomal recessive Cohen syndrome. However, the cellular distribution and
      function of the encoded protein COH1 (3997 amino acids), which lacks functional
      homologies to other mammalian proteins, have remained enigmatic. We show here
      that COH1 is a peripheral Golgi membrane protein that strongly co-localizes with
      the cis-Golgi matrix protein GM130. Consistent with its subcellular localization,
      COH1 depletion using RNAi causes fragmentation of the Golgi ribbon into
      ministacks. Disruption of Golgi organization observed in fibroblasts from Cohen
      syndrome patients suggests that Golgi dysfunction contributes to Cohen syndrome
      pathology. In conclusion, our findings establish COH1 as a Golgi-associated
      matrix protein required for Golgi integrity.

PMID- 21865174
TI  - The third transmembrane segment of orai1 protein modulates Ca2+ release-activated
      Ca2+ (CRAC) channel gating and permeation properties.
AB  - Orai1, the pore subunit of Ca(2+) release-activated Ca(2+) channels, has four
      transmembrane segments (TMs). The first segment, TMI, lines the pore and plays an
      important role in channel activation and ion permeation. TMIII, on the other
      hand, does not line the pore but still regulates channel gating and permeation
      properties. To understand the role of TMIII, we have mutated and characterized
      several residues in this domain. Mutation of Trp-176 to Cys (W176C) and Gly-183
      to Ala (G183A) had dramatic effects. Unlike wild-type channels, which exhibit
      little outward current and are activated by STIM1, W176C mutant channels
      exhibited a large outward current at positive potentials and were constitutively
      active in the absence of STIM1. G183A mutant channels also exhibited substantial
      outward currents but were active only in the presence of 2-aminoethoxydiphenyl
      borate (2-APB), irrespective of STIM1. With W176C mutant channels inward,
      monovalent currents were blocked by Ca(2+) with a high affinity similar to the
      wild type, but the Ca(2+)-dependent blocking of outward currents differed in the
      two cases. Although a 50% block of the WT outward current required 250 MUm
      Ca(2+), more than 6 mm was necessary to have the same effect on W176C mutant
      channels. In the presence of extracellular Ca(2+), W176C and G183A outward
      currents developed slowly in a voltage-dependent manner, whereas they developed
      almost instantaneously in the absence of Ca(2+). These changes in permeation and
      gating properties mimic the changes induced by mutations of Glu-190 in TMIII and
      Asp-110/Asp-112 in the TMI/TMII loop. On the basis of these data, we propose that
      TMIII maintains negatively charged residues at or near the selectivity filter in
      a conformation that facilitates Ca(2+) inward currents and prevents outward
      currents of monovalent cations. In addition, to controlling selectivity, TMIII
      may also stabilize channel gating in a closed state in the absence of STIM1 in a
      Trp-176-dependent manner.

PMID- 21865175
TI  - Pneumococcal conjugate vaccine given shortly after birth stimulates effective
      antibody concentrations and primes immunological memory for sustained infant
      protection.
AB  - BACKGROUND: In developing countries, newborn immunization with pneumococcal
      conjugate vaccines (PCVs) could protect young infants who are at high risk of
      invasive pneumococcal disease (IPD) but might lead to immune tolerance. METHODS:
      In a randomized trial, young infants received 7-valent PCV at 6, 10, and 14 weeks
      (Expanded Programme on Immunization [EPI] group) or 0, 10, and 14 weeks (newborn
      group). Safety was monitored actively at 2-7 days and then passively. Serum
      samples obtained at birth and 6, 10, 14, 18, 36, and 37 weeks were assayed by
      enzyme-linked immunosorbent assay for anticapsular immunoglobulin G concentration
      and avidity. Infants were boosted with either 7-valent PCV or one-fifth dose of
      pneumococcal polysaccharide vaccine at 36 weeks. Nasopharyngeal swab samples were
      obtained at 18 and 36 weeks. RESULTS: Three-hundred neonates and young infants
      were enrolled. Newborn vaccination was well tolerated. Adverse events occurred
      equally in each group; none was related to immunization. One infant, immunized at
      birth, died of unrelated neonatal sepsis. At 18 weeks, protective concentrations
      (>=0.35 MUg/mL) were achieved against each serotype by >=87% of infants with no
      significant differences between groups. Geometric mean concentrations were higher
      in the EPI group for serotypes 4, 9V, 18C, and 19F at 18 weeks and for serotype 4
      at 36 weeks. Avidity was greater in the newborn group for serotypes 4, 6B, and
      19F at 18 weeks and for serotype 19F at 36 weeks. Booster responses and vaccine
      type/nonvaccine-type carriage prevalence did not differ between groups.
      CONCLUSIONS: PCV was safe, immunogenic, and primed for memory when given at
      birth. There was no evidence of immune tolerance. Vaccination beginning at birth
      offers an alternative to control IPD in vulnerable young infants.

PMID- 21865176
TI  - Molecular analysis of T-DNA insertion mutants identified putative regulatory
      elements in the AtTERT gene.
AB  - Analysis of plants bearing a T-DNA insertion is a potent tool of modern molecular
      biology, providing valuable information about the function and involvement of
      genes in metabolic pathways. A collection of 12 Arabidopsis thaliana lines with T
      DNA insertions in the gene coding for the catalytic subunit of telomerase
      (AtTERT) and in adjacent regions was screened for telomerase activity [telomere
      repeat amplification protocol (TRAP) assay], telomere length (terminal
      restriction fragments), and AtTERT transcription (quantitative reverse
      transcription-PCR). Lines with the insertion located upstream of the start codon
      displayed unchanged telomere stability and telomerase activity, defining a
      putative minimal AtTERT promoter and the presence of a regulatory element linked
      to increased transcription in the line SALK_048471. Lines bearing a T-DNA
      insertion inside the protein-coding region showed telomere shortening and lack of
      telomerase activity. Transcription in most of these lines was unchanged upstream
      of the T-DNA insertion, while it was notably decreased downstream. The expression
      profile varied markedly in mutant lines harbouring insertions at the 5' end of
      AtTERT which showed increased transcription and abolished tissue specificity.
      Moreover, the line FLAG_385G01 (T-DNA insertion inside intron 1) revealed the
      presence of a highly abundant downstream transcript with normal splicing but
      without active telomerase. The role of regulatory elements found along the AtTERT
      gene is discussed in respect to natural telomerase expression and putative intron
      mediated enhancement.

PMID- 21865177
TI  - Pyrimidine degradation influences germination seedling growth and production of
      Arabidopsis seeds.
AB  - PYD1 (dihydropyrimidine dehydogenase) initiates the degradation of pyrimidine
      nucleobases and is located in plastids. In this study, a physiological analysis
      of PYD1 employing T-DNA knockout mutants and overexpressors was carried out. PYD1
      knockout mutants were restricted in degradation of exogenously provided uracil
      and accumulated high uracil levels in plant organs throughout development,
      especially in dry seeds. Moreover, PYD1 knockout mutants showed delayed
      germination which was accompanied by low invertase activity and decreased
      monosaccharide levels. Abscisic acid (ABA) is an important regulator of seed
      germination, and ABA-responsive genes were deregulated in PYD1 knockout mutants.
      Together with an observed increased PYD1 expression in wild-type seedlings upon
      ABA treatment, an interference of PYD1 with ABA signalling can be assumed.
      Constitutive PYD1 overexpression mutants showed increased growth and higher seed
      number compared with wild-type and knockout mutant plants. During senescence PYD1
      expression increased to allow uracil catabolism. From this it is concluded that
      early in development and during seed production PYD1 is needed to balance
      pyrimidine catabolism versus salvage.

PMID- 21865178
TI  - The involvement of jasmonates and ethylene in Alternaria alternata f. sp.
      lycopersici toxin-induced tomato cell death.
AB  - Previous studies have shown that an ethylene (ET)-dependent pathway is involved
      in the cell death signalling triggered by Alternaria alternata f. sp. lycopersici
      (AAL) toxin in detached tomato (Solanum lycopersicum) leaves. In this study, the
      role of jasmonic acid (JA) signalling in programmed cell death (PCD) induced by
      AAL toxin was analysed using a 35S::prosystemin transgenic line (35S::prosys), a
      JA-deficient mutant spr2, and a JA-insensitive mutant jai1. The results indicated
      that JA biosynthesis and signalling play a positive role in the AAL toxin-induced
      PCD process. In addition, treatment with the exogenous ET action inhibitor silver
      thiosulphate (STS) greatly suppressed necrotic lesions in 35S::prosys leaves,
      although 35S::prosys leaflets co-treated with AAL toxin and STS still have a
      significant high relative conductivity. Application of 1-aminocyclopropane-1
      carboxylic acid (ACC) markedly enhanced the sensitivity of spr2 and jai1 mutants
      to the toxin. However, compared with AAL toxin treatment alone, exogenous
      application of JA to the ET-insensitive mutant Never ripe (Nr) did not alter AAL
      toxin-induced cell death. In addition, the reduced ET-mediated gene expression in
      jai1 leaves was restored by co-treatment with ACC and AAL toxin. Furthermore, JA
      treatment restored the decreased expression of ET biosynthetic genes but not ET
      responsive genes in the Nr mutant compared with the toxin treatment alone. Based
      on these results, it is proposed that both JA and ET promote the AAL toxin
      induced cell death alone, and the JAI1 receptor-dependent JA pathway also acts
      upstream of ET biosynthesis in AAL toxin-triggered PCD.

PMID- 21865179
TI  - Subcellular and single-molecule imaging of plant fluorescent proteins using total
      internal reflection fluorescence microscopy (TIRFM).
AB  - Total internal reflection fluorescence microscopy (TIRFM) has been proven to be
      an extremely powerful technique in animal cell research for generating high
      contrast images and dynamic protein conformation information. However, there has
      long been a perception that TIRFM is not feasible in plant cells because the cell
      wall would restrict the penetration of the evanescent field and lead to
      scattering of illumination. By comparative analysis of epifluorescence and TIRF
      in root cells, it is demonstrated that TIRFM can generate high contrast images,
      superior to other approaches, from intact plant cells. It is also shown that TIRF
      imaging is possible not only at the plasma membrane level, but also in
      organelles, for example the nucleus, due to the presence of the central vacuole.
      Importantly, it is demonstrated for the first time that this is TIRF excitation,
      and not TIRF-like excitation described as variable-angle epifluorescence
      microscopy (VAEM), and it is shown how to distinguish the two techniques in
      practical microscopy. These TIRF images show the highest signal-to-background
      ratio, and it is demonstrated that they can be used for single-molecule
      microscopy. Rare protein events, which would otherwise be masked by the average
      molecular behaviour, can therefore be detected, including the conformations and
      oligomerization states of interacting proteins and signalling networks in vivo.
      The demonstration of the application of TIRFM and single-molecule analysis to
      plant cells therefore opens up a new range of possibilities for plant cell
      imaging.

PMID- 21865184
TI  - Invasive aspergillosis complicating pandemic influenza A (H1N1) infection in
      severely immunocompromised patients.
AB  - We report 5 cases of invasive aspergillosis occurring in severely
      immunosuppressed patients hospitalized with pandemic influenza A (H1N1). We
      suggest that infection with influenza A (H1N1) may predispose immunocompromised
      patients to develop invasive aspergillosis. Physicians should be aware of this
      potential association to allow early diagnosis and prompt treatment of
      aspergillosis.

PMID- 21865185
TI  - Early treatment with fluconazole may abrogate the development of IgG antibodies
      in coccidioidomycosis.
AB  - BACKGROUND: We have observed a number of patients who fail to develop
      coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the
      initiation of early antifungal therapy. Although this is the first description of
      this phenomenon in mycology, a precedent for the abrogation of the immune
      response has been observed in other conditions, including primary syphilis and
      primary Lyme disease. METHODS: We conducted a retrospective case-control study to
      determine any patient-specific risk factors associated with this observation.
      Additionally, in vitro analysis of the coccidioidal CF (IgG) antigen (Cts1) was
      performed after Coccidioides was grown under escalating fluconazole
      concentrations. RESULTS: Seventeen patients persistently positive for
      coccidioidal IgM antibodies without developing an IgG response (cases) were
      compared with 64 consecutive patients who did develop coccidioidal CF (IgG)
      antibodies (controls). Early treatment with antifungals (within 2 weeks of
      symptom onset) was associated with an abrogation of IgG antibody production (P <
      .001). With immunodiffusion testing, control serum demonstrated a lack of IgG
      seroreactivity when Coccidioides posadasii grown in the presence of escalating
      fluconazole doses (0.5-128 MUg/mL) was used as the antigen; however, control
      serum remained seroreactive for the presence of IgM. The coccidioidal IgG antigen
      (Cts1) was shown to be diminished when cultures were grown in the presence of
      fluconazole, lending further in vitro plausibility to our findings. CONCLUSIONS:
      The abrogation of an IgG response in patients treated early in the course of
      coccidioidal infection may complicate serodiagnosis and epidemiologic studies,
      and further study to determine the potential clinical implications should be
      performed.

PMID- 21865188
TI  - Validation of the Infectious Diseases Society of America/American Thoratic
      Society minor criteria for intensive care unit admission in community-acquired
      pneumonia patients without major criteria or contraindications to intensive care
      unit care.
AB  - BACKGROUND: The 2007 Infectious Disease Society of America/American Thoracic
      Society (IDSA/ATS) guidelines for community-acquired pneumonia (CAP) recommended
      new criteria to guide admission to the intensive care unit (ICU) for patients
      with this condition. Although the major criteria (requirement for mechanical
      ventilation or septic shock requiring vasopressor support) are well established,
      the value of the minor criteria alone have not been fully validated. METHODS: We
      performed a prospective observational study of consecutive adult patients with
      CAP admitted to NHS Lothian (Scotland, United Kingdom). Patients meeting the
      IDSA/ATS major criteria on admission were excluded, along with patients not
      suitable for ICU care owing to advanced directives or major comorbid illnesses.
      Performance characteristics for the IDSA/ATS minor criteria were calculated and
      compared with those for alternative scoring systems identified in the literature.
      Two definitions of severe CAP were used as primary end points: ICU admission, and
      subsequent requirement for mechanical ventilation or vasopressor support (MV/VS);
      30-day mortality was a secondary outcome. RESULTS: The study included 1062
      patients with CAP potentially eligible for ICU admission. Each of the 9 minor
      criteria was associated with increased risk of MV/VS and 30-day mortality in
      univariate analysis. Two hundred seven patients had >= 3 minor criteria (19.5%).
      The IDSA/ATS 2007 criteria had an area under the receiver operating
      characteristic curve of 0.85 (0.82-0.88) for prediction of MV/VS, 0.85 (0.82
      0.88) for prediction of ICU admission, and 0.78 (0.74-0.82) for prediction of 30
      day mortality. The IDSA/ATS 2007 criteria were at least equivalent to more
      established scoring systems for prediction of MV/VS and ICU admission and
      equivalent to alternative scoring systems for predicting 30-day mortality in this
      patient population. CONCLUSIONS: In a population of patients with CAP without
      contraindications to ICU care, the IDSA/ATS minor criteria predict subsequent
      requirement for MV/VS, ICU admission, and 30-day mortality.

PMID- 21865189
TI  - Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase
      producing Enterobacteriaceae.
AB  - Exposure network analysis and molecular epidemiologic methods were used to
      analyze the emergence and regional spread of Klebsiella pneumoniae carbapenemase
      producing Enterobacteriaceae over a 1-year period. Although 40 patients and 26
      health care facilities were affected, 1 long-term acute care hospital played a
      critical role in the convergence of patients at high risk, amplification by cross
      infection, and dissemination of these multidrug-resistant bacteria. BACKGROUND:
      Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are an
      emerging antibiotic resistance threat with demonstrated epidemic potential.
      METHODS: We conducted an outbreak investigation of KPC-producing
      Enterobacteriaceae among patients of acute and long-term acute care hospitals
      (LTACHs) in 4 adjacent counties in Indiana and Illinois from 1 January 2008
      through 31 December 2008 (cases). The study used traditional and molecular
      epidemiologic methods and an adaptation of social network analysis ("exposure
      network analysis"). RESULTS: Clinical records for 40 (95%) of 42 patients were
      available. Patients were mostly older with multiple comorbid conditions. Eleven
      patients (27.5%) died during the index hospitalization or were discharged to
      hospice; 23 (57.5%) were discharged to a nursing home, and 4 (10.0%) were
      discharged to home. One LTACH (LTACH-A) was central to the regional outbreak: 24
      (60%) of 40 cases were linked to LTACH-A, and at least 10 patients (25%) acquired
      KPC there. Of 16 cases not linked to LTACH-A, 12 (75%) were linked to 3 nursing
      homes. Only 4 patients (10%) definitely acquired KPC during an acute care
      hospital stay. Molecular typing revealed the 31 available KPC-positive K.
      pneumoniae isolates to be similar and to cluster with epidemic multilocus
      sequence type 258; 2 KPC-positive Escherichia coli isolates were unique.
      CONCLUSIONS: We observed extensive transfer of KPC-positive patients throughout
      the exposure network of 14 acute care hospitals, 2 LTACHs, and 10 nursing homes.
      Although few cases were identified at most institutions, many facilities were
      affected. Successful control of KPC-producing Enterobacteriaceae will require a
      coordinated, regional effort among acute and long-term health care facilities and
      public health departments.

PMID- 21865190
TI  - Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a
      whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme
      immunoassay.
AB  - BACKGROUND: Lyme disease (LD) antibody testing currently involves a 2-tiered
      algorithm with a whole-cell sonicate (WCS) enzyme immunoassay (EIA), followed by
      IgM/IgG Western immunoblots. A single EIA using the C6 peptide of the Borrelia
      burgdorferi variable-major protein-like sequence expressed lipoprotein provides
      similar or better sensitivity but less specificity, compared with standard 2
      tiered testing. Here, we investigated an alternative 2-tiered strategy, in which
      the first step remained a WCS EIA, but immunoblotting was replaced by a C6 EIA.
      METHODS: We determined the sensitivity of the 3 testing strategies with use of 91
      serum samples from research study patients with LD and 78 serum samples from
      patients with LD whose samples were submitted to our hospital's clinical
      laboratory. Specificity was measured using 54 patients with other illnesses and
      1246 healthy subjects from areas where the infection is endemic and nonendemic.
      RESULTS: The 2-EIA algorithm in early LD had similar sensitivity as C6 testing
      alone, and both strategies had better sensitivity than did standard 2-tiered
      testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late
      disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA
      algorithm was equal to that of standard 2-tiered testing, and both 2-tiered
      strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P
      = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared
      with 66% for standard 2-tiered testing and 43% for the C6 EIA alone. CONCLUSIONS:
      The 2-EIA strategy matched the individual strengths of the C6 EIA and Western
      blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to
      that of the C6 EIA but maintained the specificity of standard 2-tiered testing.

PMID- 21865191
TI  - Point-of-care measurement of blood lactate in children admitted with febrile
      illness to an African District Hospital.
AB  - BACKGROUND: Lactic acidosis is a consistent predictor of mortality owing to
      severe infectious disease, but its detection in low-income settings is limited to
      the clinical sign of "deep breathing" because of the lack of accessible
      technology for its measurement. We evaluated the use of a point-of-care (POC)
      diagnostic device for blood lactate measurement to assess the severity of illness
      in children admitted to a district hospital in Tanzania. METHODS: Children
      between the ages of 2 months and 13 years with a history of fever were enrolled
      in the study during a period of 1 year. A full clinical history and examination
      were undertaken, and blood was collected for culture, microscopy, complete blood
      cell count, and POC measurement of blood lactate and glucose. RESULTS: The study
      included 3248 children, of whom 164 (5.0%) died; 45 (27.4%) of these had raised
      levels of blood lactate (>5 mmol/L) but no deep breathing. Compared with
      mortality in children with lactate levels of <= 3 mmol/L, the unadjusted odds of
      dying were 1.6 (95% confidence interval [CI].8-3.0), 3.4 (95% CI, 1.5-7.5), and
      8.9 (95% CI, 4.7-16.8) in children with blood lactate levels of 3.1-5.0, 5.1-8.0,
      or >8.0 mmol/L, respectively. The prevalence of raised lactate levels (>5 mmol/L)
      was greater in children with malaria than in children with nonmalarial febrile
      illness (P < .001) although the associated mortality was greater in slide
      negative children. CONCLUSIONS: POC lactate measurement can contribute to the
      assessment of children admitted to hospital with febrile illness and can also
      create an opportunity for more hospitals in resource-poor settings to participate
      in clinical trials of interventions to reduce mortality associated with
      hyperlactatemia.

PMID- 21865192
TI  - Current diagnosis and management of peripheral tuberculous lymphadenitis.
AB  - Peripheral tuberculous lymphadenitis accounts for ~10% of tuberculosis cases in
      the United States. Epidemiologic characteristics include a 1.4:1 female-to-male
      ratio, a peak age range of 30-40 years, and dominant foreign birth, especially
      East Asian. Patients present with a 1-2 month history of painless swelling of a
      single group of cervical lymph nodes. Definitive diagnosis is by culture or
      nucleic amplification of Mycobacterium tuberculosis; demonstration of acid fast
      bacilli and granulomatous inflammation may be helpful. Excisional biopsy has the
      highest sensitivity at 80%, but fine-needle aspiration is less invasive and may
      be useful, especially in immunocompromised hosts and in resource-limited
      settings. Antimycobacterial therapy remains the cornerstone of treatment, but
      response is slower than with pulmonary tuberculosis; persistent pain and swelling
      are common, and paradoxical upgrading reactions may occur in 20% of patients. The
      role of steroids is controversial. Initial excisional biopsy deserves
      consideration for both optimal diagnosis and management of the otherwise slow
      response to therapy.

PMID- 21865193
TI  - Failure of the Milwaukee protocol in a child with rabies.
AB  - Rabies has the highest case-fatality rate of all infectious diseases, with 50,000
      cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived
      after novel therapy. We report the management of a child with rabies. Although
      the implementation of this same therapeutic protocol was successful, the child
      died after 1 month of hospitalization.

PMID- 21865194
TI  - PHOTO QUIZ. A diagnosis made in vein. Schistosoma haematobium infection
      (Bilharzias).

PMID- 21865195
TI  - The interface between antibiotic resistance and virulence in Staphylococcus
      aureus and its impact upon clinical outcomes.
AB  - The ability of Staphylococcus aureus to rapidly acquire antibiotic resistance in
      the face of antimicrobial challenge has enabled it to remain an ongoing,
      significant human pathogen. Mechanisms behind the evolution of resistance in S.
      aureus are well documented, but the effects of these phenotypes upon virulence
      are less clear. By exploring available clinical and experimental data, we have
      shown that a number of the major steps in the evolution of antibacterial
      resistance in S. aureus have been accompanied by alterations in virulence. This
      review also highlights that further experimentation is required to fully
      elucidate the mechanisms involved in the interface between virulence and
      antibiotic resistance, with the intention of identifying novel preventative or
      therapeutic strategies for this important human pathogen.

PMID- 21865196
TI  - Transfusion-transmitted Yersinia enterocolitica sepsis.
AB  - Bacterial sepsis has become the most frequent infectious complication of
      transfusion. Although Yersinia enterocolitica is a common enteropathogen usually
      causing relatively mild disease, it is nevertheless a prominent cause of life
      threatening post-transfusion infection. To gain a better understanding of the
      clinical presentation and prognosis of this rare occurrence, we performed a
      systematic and detailed review of 55 published cases, which we present here after
      a description of the mechanisms underlying the contamination of red blood cell
      preparations by Y. enterocolitica. The symptoms are rapid-onset septic shock
      sometimes heralded by atypical symptoms, such as explosive diarrhea, with an
      overall fatality rate of 54.5%. Although the pathophysiology involves transfusion
      of preformed bacterial endotoxin, timely administration of effective antibiotics
      seems to improve the prognosis. Increased vigilance of the blood supply could
      help mitigate this transfusion hazard, although cost-effective strategies are
      difficult to define for this highly serious but infrequent event.

PMID- 21865198
TI  - Letter to Mendeni et al.

PMID- 21865199
TI  - Methodological issues in corneal collagen crosslinking in post-LASIK
      keratectasia.

PMID- 21865201
TI  - The 'I' of the beholder: studying the 'self' across the humanities and
      neuroscience.
AB  - Long debated within the humanistic tradition, the concept of 'self' has recently
      been embraced as a subject of investigation by cognitive neuroscience. Tracing
      parallels between ancient philosophical ideas and current-day scientific research
      on the 'self', the author proposes that contemporary knowledge based on empirical
      neuroscientific evidence may inform novel perspectives on-and draw inspiration
      from-notions grounded in ancient intuitions and traditionally falling within
      humanistic fields of enquiry. Further, the author suggests that the 'self', as a
      major object of philosophical and psychological enquiry, as well as a central
      component of human motivation, cognition, affect and social identity, is an
      inherently cross-disciplinary research topic, which, by virtue of its pervasive
      and defining presence in human existence, lends itself-and demands-to be
      approached both from scientific (objective) and phenomenological (subjective)
      vantage points. On this premise, the author proposes that the study of the 'self'
      provides both neuroscientists and humanists with a fertile ground for cross
      disciplinary research, and with the challenge and the opportunity to rethink the
      relationship of science to knowledge.

PMID- 21865200
TI  - Age-related macular degeneration: the importance of family history as a risk
      factor.
AB  - BACKGROUND: Family history is considered a risk factor for age-related macular
      degeneration (AMD). With the advent of effective therapy for the disease, the
      importance of family history merits further investigation. This study quantifies
      the risk associated with family history, first, by a case-control study of
      reported family history and, second, by examining the siblings of AMD cases.
      METHODS: The authors recruited cases with advanced AMD, spouses and siblings. All
      subjects were carefully phenotyped. Clinical findings in the siblings were
      compared with spouses. Information about family history was collected. The ORs
      for reported family history of AMD were calculated. Analyses were adjusted for
      age, smoking and genotype. RESULTS: 495 AMD cases, 259 spouses and 171 siblings
      were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a
      reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001)
      with a history of an affected sibling. ORs adjusted for age and smoking were
      higher. Examination of siblings confirmed their increased risk with 23% affected
      by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the
      OR to 16.1 (6.2 to 41.8). CONCLUSION: The risk of AMD is greatly increased by
      having an affected first-degree relative. Those at risk need to be made aware of
      this and AMD patients should advise siblings and children to seek prompt
      ophthalmological advice if they develop visual symptoms of distortion or reduced
      vision.

PMID- 21865202
TI  - Do antioxidant vitamins have an anti-arrhythmic effect following cardiac surgery?
      A meta-analysis of randomised controlled trials.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF) affects approximately 30% of
      patients undergoing elective cardiac surgery. While its pathogenesis is
      multifactorial, increasing evidence supports a role for oxidative stress in the
      electrophysiological remodelling associated with AF. Although prophylactic
      antioxidants appear to be a potentially attractive pharmacotherapy, there is
      still uncertainty regarding their efficacy. This study aims to provide a
      quantitative summary of the current evidence surrounding antioxidant vitamins and
      POAF prevention. METHODS: A systematic literature review identified five
      randomised controlled trials incorporating 567 patients (n = 284 antioxidant, n =
      283 control). These were meta-analysed using random effects modelling.
      Heterogeneity, subgroup analysis, quality scoring and risk of bias were assessed.
      Primary endpoints were the incidence of POAF and all-cause arrhythmia. Secondary
      endpoints were length of stay in the intensive care unit (ITU) and length of
      hospital stay. RESULTS: Vitamins C and E significantly reduced the incidence of
      POAF (OR 0.43, 95% CI 0.21 to 0.89) and all-cause arrhythmia (OR 0.54, 95% CI
      0.29 to 0.99) compared with controls. A significant reduction in both ITU stay
      (weighted mean difference (WMD) -0.44, 95% CI -0.70 to -0.17) and hospital stay
      (WMD -1.11, 95% CI -1.70 to -0.52) was also seen in the antioxidant group,
      without significant heterogeneity. CONCLUSIONS: The prophylactic use of vitamins
      C and E may significantly reduce the incidence of POAF and all-cause arrhythmia
      following cardiac surgery. However, the overall quality of current studies is
      poor and further research should focus on adequately powered randomised
      controlled trials that standardise AF reporting, antioxidant protocol and the use
      of concomitant agents. Cost analysis should be considered to establish the
      potential economic benefit of antioxidant vitamin prophylaxis in POAF.

PMID- 21865204
TI  - Response to the recent best evidence topic on the use of thrombolysis in stroke.

PMID- 21865203
TI  - Central obesity and cardiovascular outcomes in patients with acute coronary
      syndrome: observations from the MERLIN-TIMI 36 trial.
AB  - OBJECTIVE: Despite the association of obesity with incident cardiovascular
      disease, obese patients with acute coronary syndrome (ACS) appear to have more
      favourable short-term outcomes. A study was undertaken to determine whether this
      'obesity paradox' persists in the long term and to examine the specific
      relationship of central obesity with outcomes after ACS. METHODS: The
      relationship was investigated between two measures of obesity-body mass index
      (BMI) and waist circumference (WC)-and 30-day and 1-year outcomes after ACS. 6560
      patients with non-ST elevation ACS in the MERLIN-TIMI 36 trial were followed for
      1 year. Patients were stratified into three BMI groups (<25, 25-30, >=30 kg/m2)
      and gender-specific tertiles of WC. The primary endpoint was cardiovascular
      death, myocardial infarction or recurrent ischaemia. RESULTS: Patients with BMI
      >=30 kg/m2 had a significantly lower risk of the primary endpoint than those with
      BMI <25 kg/m(2) (HR 0.64; 95% CI 0.51 to 0.81, p<0.0001) at 30 days. However,
      after the 30-day acute phase, landmark analysis from 30 days to 1 year showed no
      difference in risk between BMI groups (HR 1.09; 95% CI 0.92 to 1.29, p=0.34). WC
      tertiles demonstrated a similar relationship. When BMI groups were stratified by
      WC there was a trend towards more adverse outcomes in higher WC groups among
      those in lower BMI groups. The group with the lowest BMI and highest WC had the
      highest risk (HR 2.8; 95% CI 0.93 to 8.3; p=0.067). CONCLUSIONS: Obesity is
      associated with more favourable short-term outcomes after ACS. However, in the
      longer term the obesity paradox is no longer present and may reverse. Those with
      WC out of proportion to BMI suggestive of significant central adiposity may be at
      highest risk following ACS.

PMID- 21865205
TI  - Factors associated with use of slip-resistant shoes in US limited-service
      restaurant workers.
AB  - OBJECTIVES: Slips and falls are a leading cause of injury at work. Several
      studies have indicated that slip-resistant shoes can reduce the risk of
      occupational slips and falls. Few studies, however, have examined the
      determinants of slip-resistant shoe use. This study examined the individual and
      workplace factors associated with slip-resistant shoe use. METHODS: 475 workers
      from 36 limited-service restaurants in the USA participated in a study of
      workplace slipping. Demographic and job characteristic information about each
      participant was collected. Restaurant managers provided information on whether
      slip-resistant shoes were provided and paid for by the employer and whether any
      guidance was given regarding slip-resistant shoe use when they were not provided.
      Kitchen floor coefficient of friction was measured. Slip-resistant status of the
      shoes was determined by noting the presence of a 'slip-resistant' marking on the
      sole. Poisson regression with robust SE was used to calculate prevalence ratios.
      RESULTS: 320 participants wore slip-resistant shoes (67%). In the multivariate
      analysis, the prevalence of slip-resistant shoe use was lowest in 15-19-year age
      group. Women were more likely to wear slip-resistant shoes (prevalence ratio
      1.18, 95% CI 1.07 to 1.31). The prevalence of slip-resistant shoe use was lower
      when no guidance regarding slip-resistant shoes was given as compared to when
      they were provided by the employer (prevalence ratio 0.66, 95% CI 0.55 to 0.79).
      Education level, job tenure and the mean coefficient of friction had no
      significant effects on the use of slip-resistant shoes. CONCLUSION: Provision of
      slip-resistant shoes was the strongest predictor of their use. Given their
      effectiveness and low cost, employers should consider providing slip-resistant
      shoes at work.

PMID- 21865206
TI  - Measuring the cost of injury: underestimating the costs of street violence.

PMID- 21865207
TI  - Primary airway epithelial cultures from children are highly permissive to
      respiratory syncytial virus infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection of airway epithelial
      cells (AECs) is an important initial event in RSV bronchiolitis. AEC
      immunological responses are thought to be critical in driving the subsequent
      inflammation in the airway. This study examined viral replication, cytotoxicity
      and cytokine production in cultures of primary AECs from children compared with
      responses to RSV infection in an immortalised epithelial cell line and to those
      from infants with RSV bronchiolitis. METHODS: RSV replication, proinflammatory
      cytokine responses and cytotoxicity in RSV-infected primary AEC cultures derived
      from bronchial brushings from the lungs of children were compared with those seen
      in BEAS-2B cultures, as well as AECs and bronchoalveolar lavage fluid collected
      from children with and without RSV bronchiolitis. RESULTS: Viral replication,
      cytotoxicity and inflammatory cytokine production were greater in primary AEC
      cultures than in BEAS-2B cells. Different response patterns were observed, with
      RSV infection of primary AEC cultures causing distinct peaks of viral replication
      and matched cytotoxic responses. Some primary AEC culture immunological
      responses, such as interleukin 8, were similar in magnitude to those seen in
      clinical samples from the lungs of children with RSV bronchiolitis. Although
      variable amounts of RSV were detected by PCR in freshly isolated primary AECs,
      RSV was not detected by immunocytochemistry. CONCLUSION: This is one of the first
      studies to examine comprehensively the responses to RSV infection in primary AEC
      cultures from children and shows marked differences from those of a commercially
      available immortalised human cell line but reassuring similarities to results
      found in vivo. This suggests that future work investigating responses of AECs to
      RSV infection should use primary AEC cultures.

PMID- 21865209
TI  - Pragmatic trials: how to adjust for the 'Hawthorne effect'?

PMID- 21865211
TI  - Treatment effect of natalizumab on relapse outcomes in multiple sclerosis
      patients despite ongoing MRI activity.
AB  - Natalizumab treatment significantly reduced the annualised relapse rate and MRI
      activity over 2 years compared with placebo in phase III trials when administered
      as monotherapy in AFFIRM or in combination with interferon beta-1a (IFNbeta) in
      SENTINEL. The post hoc analyses reported here sought to determine the effect of
      natalizumab treatment on relapse activity in the minority of patients who
      continued to show MRI activity (ie, >= 1 gadolinium enhancing (Gd+) lesions or
      new or enlarging T2 hyperintense lesions) over 2 years in these trials. These
      analyses demonstrated that natalizumab treatment, both alone (AFFIRM) and in
      combination with IFNbeta (SENTINEL), resulted in a reduced annualised relapse
      rate despite the presence of Gd+ lesions (p=0.004 and p=0.008, respectively) or
      new or enlarging T2 hyperintense lesions (each p<0.0001). Thus patients treated
      with natalizumab show clinical benefit even in the presence of continued MRI
      activity. Long term clinical outcome of these patients has not been studied.

PMID- 21865212
TI  - Relative mortality and survival in multiple sclerosis: findings from British
      Columbia, Canada.
AB  - OBJECTIVE: To examine mortality and factors associated with survival in a
      population based multiple sclerosis (MS) cohort. METHODS: Clinical and
      demographic data of MS patients registered with the British Columbia MS clinics
      (1980-2004) were linked to provincial death data, and patients were followed
      until death, emigration or study end (31 December 2007). Absolute survival and
      the influence of patient characteristics (sex, disease course (primary
      progressive (PPMS) vs relapsing onset (R-MS)) and onset age) were estimated by
      Kaplan-Meier analyses (from birth and disease onset). Mortality relative to the
      general population was examined using standardised mortality ratios. Excess
      mortality associated with patient characteristics and time period of cohort entry
      was assessed by relative survival modelling. RESULTS: Of 6917 patients, 1025
      died. Median survival age was 78.6 years (95% CI 77.5 to 79.7) for women and 74.3
      years (95% CI 73.1 to 75.4) for men. Survival from onset was longer for R-MS
      (49.7 years; 95% CI 47.9 to 51.5) than for PPMS (32.5 years; 95% CI 29.5 to
      35.7); however, survival age was similar. The overall standardised mortality
      ratios was 2.89 (95% CI 2.71 to 3.07), and patients survived approximately 6
      years less than expected, relative to the general population. PPMS had a higher
      relative mortality risk compared with R-MS (relative mortality ratio (RMR) 1.52;
      95% CI 1.30 to 1.80). Women with PPMS had a relative survival disadvantage
      compared with men with PPMS (RMR 1.55; 95% CI 1.19 to 2.01). Relative survival
      within 10 years of cohort entry was similar between time periods. CONCLUSIONS:
      Some of the longest MS survival times are reported here but the risk of death was
      still greater than in the age, sex and calendar year matched general population.
      No evidence of increased survival over time was found when improved survival in
      the general population was taken into consideration.

PMID- 21865213
TI  - Genetic basis of Bartter syndrome in Korea.
AB  - BACKGROUND: Bartter syndrome (BS) is clinically classified into antenatal or
      neonatal BS (aBS) and classic BS (cBS) as well as five subtypes based on the
      underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III), BSND (BS
      IV) and CASR (BS V). METHODS: Clinico-genetic features of a nationwide cohort of
      26 Korean children with BS were investigated. RESULTS: The clinical diagnosis was
      aBS in 8 (30.8%), cBS in 15 (57.7%) and mixed Bartter-Gitelman phenotype in 3
      cases (11.5%). Five of eight patients with aBS and all 18 patients with either
      cBS or mixed Bartter-Gitelman phenotype had CLCNKB mutations. Among the 23
      patients (46 alleles) with CLCNKB mutations, p.W610X and large deletions were
      detected in 25 (54.3%) and 10 (21.7%) alleles, respectively. There was no
      genotype-phenotype correlation in patients with CLCNKB mutations. CONCLUSIONS:
      Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB
      mutations. The p.W610X mutation and large deletion were two common types of
      mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous
      without a genotype-phenotype correlation, typically manifesting cBS phenotype but
      also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for
      patients with BS in our population should be designed taking these peculiar
      genotype distributions into consideration, and a new more clinically relevant
      classification including BS and Gitelman syndrome is required.

PMID- 21865214
TI  - High frequency of aspirin resistance in patients with nephrotic syndrome.
AB  - BACKGROUND: Aspirin has a beneficial role in prevention of cardiovascular and
      thromboembolic events. Patients may experience thromboembolic events despite
      aspirin treatment, a phenomenon called aspirin resistance. We evaluated the
      frequency of aspirin resistance and its correlation with clinical and biochemical
      parameters among patients with nephrotic syndrome (NS). METHODS: A total of 83
      patients (50 males, 33 females, age range 18-79 years) with NS using aspirin 100
      mg/day were included in the study. Demographic information and aetiology of NS
      based on the histology of a renal biopsy were recorded for each patient. Blood
      samples were drawn to investigate the association of aspirin resistance with
      inflammation and thrombotic risk factors. Aspirin resistance was defined as a
      normal collagen/epinephrine closure time<159 s using a platelet function analyzer
      (PFA-100). RESULTS: Aspirin resistance was determined in 51 patients (61.4%). The
      number of patients exposed to azathioprine therapy was significantly higher in
      the aspirin-sensitive group (P=0.043), whereas patients exposed to cyclosporine
      therapy were significantly higher in the aspirin-resistant group (P=0.017). More
      patients in the aspirin-resistant group were on angiotensin-converting enzyme
      inhibitor therapy compared with the aspirin-sensitive group (P=0.024). The
      aspirin-resistant group showed significantly higher serum low-density lipoprotein
      cholesterol (LDL-C) (151+/-47 versus 104+/-21 mg/dL; P<0.001), triglyceride
      levels (192+/-116 versus 134+/-82 mg/dL; P=0.015) and glomerular filtration rates
      (91.8+/-43.0 versus 74.0+/-35.6 mL/min/1.73 m2; P=0.044) compared with the
      aspirin-sensitive group. In multivariate analysis, LDL-C was the only parameter
      associated independently with aspirin resistance [odds ratio (OR) 1.04, 95%
      confidence interval (CI) 1.02-1.06; P=0.004]. CONCLUSIONS: A significant number
      of patients with NS are resistant to aspirin therapy. Serum LDL-C level is
      closely associated with aspirin resistance in NS.

PMID- 21865215
TI  - The effect of timing of the first kidney transplantation on survival in children
      initiating renal replacement therapy.
AB  - BACKGROUND: Controversy exists concerning the timing of the first kidney
      transplantation for children who need to start renal replacement therapy (RRT).
      Our aim was to estimate the effect of timing of the first transplantation on
      patient survival in children, for the first time also taking into account the
      mortality on dialysis before transplantation. METHODS: We included 2091 patients
      who started RRT between the age of 3 and 18 years in the period 1988-2007, from
      13 European renal registries. A multistate model was used to simulate patient
      survival assuming (i) pre-emptive transplantation, (ii) transplantation after 1
      or 2 years on dialysis and (iii) remaining on dialysis. RESULTS: Over the 20-year
      period, the highest 8-year survival probabilities were achieved in children
      transplanted pre-emptively {living donor (LD): 95.9% [95% confidence interval
      (CI): 93.1-98.8], deceased donor (DD): 95.3% (95% CI: 90.9-99.9)} rather than
      after 2 years of dialysis [LD: 94.2% (95% CI: 91.6-96.8), DD: 93.4% (95% CI: 91.0
      95.9)], although these differences were not statistically significant.
      CONCLUSIONS: Even after taking mortality on dialysis into account, the
      potentially negative effect of postponing transplantation for 1 or 2 years was
      relatively small and not statistically significant. Therefore, if pre-emptive
      transplantation is not possible, starting RRT with a short period of dialysis and
      receiving a transplant thereafter seems an acceptable alternative from the
      perspective of patient survival.

PMID- 21865216
TI  - What influences patient choice of treatment modality at the pre-dialysis stage?
AB  - BACKGROUND: There is little information on factors influencing patient choice of
      renal replacement modality (RRM) in the UK. Pre-dialysis education programmes
      have been associated with increased uptake of peritoneal dialysis (PD) in other
      countries but their relevance in informing patient choice within UK centres has
      not been extensively studied. In this study, we examined how patient choice of
      different treatment modalities [haemodialysis (HD), PD and conservative
      management (CM)] is influenced by personal and demographic parameters. METHODS:
      Questionnaires were sent to 242 pre-dialysis patients from a single centre.
      Patients were asked to rate factors affecting their treatment choice.
      Demographics, functional status, educational day attendance and Charlson index
      (CI) scores were also collected. RESULTS: One hundred and eighteen replies were
      received. Seventy per cent of patients had chosen HD, 20% PD and 10% had opted
      for CM. There was a clear association between age and modality choice. Mean age
      of patients choosing PD was 55 years compared to 68 years for HD and 84 years for
      CM (P<0.001). Similarly, the degree of co-morbidity was linked with treatment
      choice, with patients choosing PD having a mean CI score of 4.1 compared to 5.8
      among HD patients and 7.7 for CM (P<0.001). Factors rated as important by all
      three groups were: the ability to cope, fitting modality with lifestyle, distance
      to centre and verbal and written information about modality. Conversely, factors
      rated as not important by all groups were: use of internet, religious beliefs and
      friends' views. Using analysis of variance, there was a statistically significant
      variance between the HD and the PD group responses in the following factors:
      provision of written information (P=0.048), fitting modality with lifestyle
      (P=0.025), family/home/work circumstances (P=0.003) and past medical history
      (P=0.018). Fifty per cent of patients who chose PD attended a formal education
      day compared to 32.9% that chose HD and 0% that chose CM (P=0.011). The following
      demographic factors were crucial in predicting RRM choice: being married (PD
      95.7%, HD 53.8%, CM 41.7%; P<0.001), being employed (PD 33.3%, HD 11.5%, CM 0%;
      P=0.015) and having another person living at home (PD 100%, HD 69.5%, CM 50%;
      P=0.003). Patients who have had a social services assessment in the last 12
      months or received private care services or disability allowance were more likely
      to choose CM. CONCLUSIONS: This study highlights important factors influencing
      patient choice of end-stage renal disease treatment modality including CM. While
      some of these are non-modifiable, such as age and degree of co-morbidity, others
      draw attention to the importance of good information provision and pre-dialysis
      education in empowering socially able patients to choose self-care therapies.
      Furthermore, the overwhelming association of having a strong social support
      network and being functionally able with choosing PD emphasizes the need for
      assisted PD.

PMID- 21865217
TI  - How plant architecture affects light absorption and photosynthesis in tomato:
      towards an ideotype for plant architecture using a functional-structural plant
      model.
AB  - BACKGROUND AND AIMS: Manipulation of plant structure can strongly affect light
      distribution in the canopy and photosynthesis. The aim of this paper is to find a
      plant ideotype for optimization of light absorption and canopy photosynthesis.
      Using a static functional structural plant model (FSPM), a range of different
      plant architectural characteristics was tested for two different seasons in order
      to find the optimal architecture with respect to light absorption and
      photosynthesis. METHODS: Simulations were performed with an FSPM of a greenhouse
      grown tomato crop. Sensitivity analyses were carried out for leaf elevation
      angle, leaf phyllotaxis, leaflet angle, leaf shape, leaflet arrangement and
      internode length. From the results of this analysis two possible ideotypes were
      proposed. Four different vertical light distributions were also tested, while
      light absorption cumulated over the whole canopy was kept the same. KEY RESULTS:
      Photosynthesis was augmented by 6 % in winter and reduced by 7 % in summer, when
      light absorption in the top part of the canopy was increased by 25 %, while not
      changing light absorption of the canopy as a whole. The measured plant structure
      was already optimal with respect to leaf elevation angle, leaflet angle and
      leaflet arrangement for both light absorption and photosynthesis while
      phyllotaxis had no effect. Increasing the length : width ratio of leaves by 1.5
      or increasing internode length from 7 cm to 12 cm led to an increase of 6-10 %
      for light absorption and photosynthesis. CONCLUSIONS: At high light intensities
      (summer) deeper penetration of light in the canopy improves crop photosynthesis,
      but not at low light intensities (winter). In particular, internode length and
      leaf shape affect the vertical distribution of light in the canopy. A new plant
      ideotype with more spacious canopy architecture due to long internodes and long
      and narrow leaves led to an increase in crop photosynthesis of up to 10 %.

PMID- 21865219
TI  - Introduction of endobronchial ultrasonography (EBUS) in bronchoscopy clearly
      reduces fluoroscopy time: comparison of 147 cases in groups before and after EBUS
      introduction.
AB  - BACKGROUND: Endobronchial ultrasonography (EBUS) has been used in diagnosing
      peripheral lung cancer and has allowed for higher rates of peripheral lung cancer
      diagnosis. However, no studies have reported that fluoroscopy time is shortened
      by the use of endobronchial ultrasonography. We aimed to investigate whether
      fluoroscopy time is shortened using endobronchial ultrasonography. METHODS: We
      retrospectively researched fluoroscopy time in terms of the rate of diagnosis,
      lesion size, age, gender, histologic type and lesion site in 147 cases of
      malignant lesions from January 2006 to September 2007 at the Tokai University
      Hospital. The location of the bronchial brush or biopsy forceps was confirmed by
      fluoroscopy without endobronchial ultrasonography with guide-sheath group in 96
      of the 147 cases, while fluoroscopy with endobronchial ultrasonography guide
      sheath group was confirmed in 51 cases. RESULTS: The result was that fluoroscopy
      time was significantly shortened in the endobronchial ultrasonography guide
      sheath group (4.08 +/- 3.27 min) compared with the non-endobronchial
      ultrasonography guide-sheath group (7.06 +/- 3.99 min), but there was no
      significant difference between either groups in terms of bronchoscopic diagnosis,
      lesion size, age, gender, histologic type and lesion site. CONCLUSION: The use of
      endobronchial ultrasonography guide sheath allows a reduction in fluoroscopy time
      and may reduce the adverse effects of radiation exposure on patients and staff.

PMID- 21865218
TI  - How good is the turbid medium-based approach for accounting for light
      partitioning in contrasted grass--legume intercropping systems?
AB  - BACKGROUND AND AIMS: Most studies dealing with light partitioning in
      intercropping systems have used statistical models based on the turbid medium
      approach, thus assuming homogeneous canopies. However, these models could not be
      directly validated although spatial heterogeneities could arise in such canopies.
      The aim of the present study was to assess the ability of the turbid medium
      approach to accurately estimate light partitioning within grass-legume mixed
      canopies. METHODS: Three contrasted mixtures of wheat-pea, tall fescue-alfalfa
      and tall fescue-clover were sown according to various patterns and densities.
      Three-dimensional plant mock-ups were derived from magnetic digitizations carried
      out at different stages of development. The benchmarks for light interception
      efficiency (LIE) estimates were provided by the combination of a light projective
      model and plant mock-ups, which also provided the inputs of a turbid medium model
      (SIRASCA), i.e. leaf area index and inclination. SIRASCA was set to gradually
      account for vertical heterogeneity of the foliage, i.e. the canopy was described
      as one, two or ten horizontal layers of leaves. KEY RESULTS: Mixtures exhibited
      various and heterogeneous profiles of foliar distribution, leaf inclination and
      component species height. Nevertheless, most of the LIE was satisfactorily
      predicted by SIRASCA. Biased estimations were, however, observed for (1) grass
      species and (2) tall fescue-alfalfa mixtures grown at high density. Most of the
      discrepancies were due to vertical heterogeneities and were corrected by
      increasing the vertical description of canopies although, in practice, this would
      require time-consuming measurements. CONCLUSIONS: The turbid medium analogy could
      be successfully used in a wide range of canopies. However, a more detailed
      description of the canopy is required for mixtures exhibiting vertical
      stratifications and inter-/intra-species foliage overlapping. Architectural
      models remain a relevant tool for studying light partitioning in intercropping
      systems that exhibit strong vertical heterogeneities. Moreover, these models
      offer the possibility to integrate the effects of microclimate variations on
      plant growth.

PMID- 21865220
TI  - A US-UK comparison of health in 1990-1991 Gulf War veterans.
AB  - BACKGROUND: UK and US military personnel appear to have different health profiles
      yet direct comparisons of health status and deployment exposures between US and
      UK military populations have never been performed. AIMS: To compare US and UK
      military personnel deployed to the 1991 Persian Gulf War (PGW) for rates of
      symptom reporting, medical conditions and health status [Short Form-36 general
      health perception (GHP) and physical functioning (PF) subscales] and self-report
      military exposures. METHODS: We analysed representative cross-sectional samples
      of military personnel from the Iowa Persian Gulf Study (n = 3626) and the UK
      Health Survey of Military Personnel (n = 5573) that included directly comparable
      measures and stratified by those who had been deployed to PGW and those who had
      not been deployed to PGW. RESULTS: Although UK veterans had similar mean PF
      scores as US veterans (mean differences in PGW: 0.86, 95% CI -0.36 to 2.07 and in
      non-deployed -0.61, 95% CI -1.84 to 0.62), they had worse mean GHP scores (mean
      differences in PGW: -5.62, 95% CI -7.44 to -3.80 and in non-deployed -3.83, 95%
      CI -5.40 to -2.27). UK PGW veterans were more likely to report Gulf specific
      exposures, and this was associated with worse GHP (UK mean difference -9.05, 95%
      CI -11.49 to -6.61 versus US mean difference -4.30, 95% CI -6.62 to -1.98).
      CONCLUSIONS: This study observed transatlantic variations in health status in
      military populations that may reflect cultural differences in the reporting of
      health.

PMID- 21865221
TI  - Sickness absence among Finnish special and general education teachers.
AB  - BACKGROUND: Although teaching is considered a high-stress profession, research on
      stress-related outcomes among teachers, such as absence from work due to illness
      (i.e. sickness absence), remains scarce. It is possible that teachers are not a
      homogeneous group but include subgroups with particularly high risk of sickness
      absence, such as special education teachers. AIMS: To examine differences in
      sickness absence rates between special and general education teachers in a large
      cohort of 2291 Finnish lower secondary school teachers. METHODS: Register data on
      teachers' job titles, sociodemographic characteristics and sickness absence were
      obtained from 10 municipal employers' registers. Indices of sickness absence
      included rates of short-term (1-3 days) and long-term (>3 days) absence spells
      during 2003-05. RESULTS: With multi-level models adjusted for individual- and
      school-level covariates, we found that although the absolute level of sickness
      absence was higher among women than among men, male special education teachers
      were at a 1.36-fold (95% CI: 1.15-1.61) increased risk of short-term and a 1.33
      fold (95% CI: 1.01-1.76) increased risk of long-term sickness absence compared
      with male teachers in general education. Among women, there were no differences
      in sickness absence between special and general education teachers. CONCLUSIONS:
      Compared to male teachers in general education, male teachers in special
      education appear to have an excess risk of absence from work due to illness.
      Future studies should examine the causes for this excess risk and determine the
      need for preventive interventions.

PMID- 21865222
TI  - Work-related health advice in primary care.
AB  - BACKGROUND: The dangers of long-term sickness absence and worklessness are well
      recognized. In the UK, the occupational health (OH) community was challenged to
      seek new partners to support health in working age people. A National Health
      Service OH service and Leicestershire general practice set up a pilot clinic to
      provide work-related health advice in primary care. AIMS: To recruit 100 patients
      to an OH clinic in general practice and record their demographic characteristics,
      diagnoses and occupational outcomes. METHODS: Pre-booked 30 min appointments for
      work-related health consultations in general practice were offered over 12
      months. Consultations were recorded electronically and questionnaire feedback
      invited 3-6 months later. The main outcome was subjective reporting of benefit
      and workplace adjustments. RESULTS: Ninety-six patients attended OH appointments
      in general practice, 86 were in employment: 49 on sick leave at the time of their
      consultation and 10 were workless. Mental health and musculoskeletal problems
      accounted for the most common diagnoses. Following their consultation, 29% of
      patients reported workplace adjustments which were beneficial to them. None of
      the workless reported a return to employment. CONCLUSIONS: Patients will access
      work-related health advice in primary care. Extended OH consultations by general
      practitioners can achieve positive self-reported outcomes for patients in
      employment.

PMID- 21865223
TI  - Human cell-death-inducing DFF45-like effector C induces apoptosis via caspase-8.
AB  - Human cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector C
      (CIDEC) is a potent apoptotic inducer. Previous studies have indicated that the
      Fat-specific protein 27 (Fsp27), a mouse homolog of CIDEC, induces apoptosis via
      caspase-3, -7, and -9 and triggers the release of cytochrome c from mitochondria,
      which implies that the mitochondrial pathway is involved in Fsp27-induced
      apoptosis. In the current study, we found that CIDEC-induced apoptosis was
      mediated by caspase-8. The caspase inhibitor assay showed that CIDEC-induced
      apoptosis was dramatically reduced in the presence of the general caspase
      inhibitor, the caspase-3 inhibitor, and the caspase-8 inhibitor, whereas the
      caspase-9 inhibitor only weakly inhibited CIDEC-induced apoptosis. These results
      confirmed that the activation of caspase-3 and caspase-8 were involved in CIDEC
      induced apoptosis. Moreover, in caspase-3- or caspase-8-deficient cells, CIDEC
      induced apoptosis were dramatically decreased, which demonstrated that CIDEC
      induced apoptosis might require the activation of caspase-3 and caspase-8.
      Because caspase-8 in general is a key effecter of death-receptor pathway and
      activated by Fas-Associated protein with Death Domain (FADD), we examined whether
      FADD was involved in CIDEC-induced apoptosis. Our results demonstrated that CIDEC
      induced apoptosis was independent of FADD, suggesting that CIDEC-induced
      apoptosis might be in a death-receptor-independent, caspase-8-dependent manner.
      It was also found that the region of amino acid 168-200 in carboxyl domain of
      CIDEC was critical for its crucial pro-apoptotic function.

PMID- 21865225
TI  - Reverse remodelling induces progressive ventricular resynchronization after
      cardiac resynchronization therapy 'from vicious to virtuous cycle'.
AB  - AIMS: Cardiac resynchronization therapy (CRT) can stop the vicious cycle
      resulting from dyssynchrony and generates left ventricular (LV) reverse
      remodelling. Our objective was to assess the time course and the relationship
      between improvement in LV dyssynchrony and reverse remodelling after CRT. METHODS
      AND RESULTS: Sixty-four consecutive patients were evaluated before, immediately
      after, and 3- and 6 months after CRT. We measured LV volumes, ejection fraction
      (EF), and sphericity index, and dyssynchrony was assessed using speckle-tracking
      radial strain. Response was defined as a >15% decrease in end-systolic volume
      (ESV) 6 months after CRT, and event-free survival was followed for 24 months.
      Responders and non-responders had similar baseline LV volumes and EF. During the
      first and the following 3 months after CRT, LV volumes gradually decreased (end
      diastolic volume: 195+/-73 to 164+/-60* to 129+/-51 mL?, ESV: 141+/-70 to 110+/
      47* to 82+/-40 mL?), and sphericity index and EF progressively increased
      (sphericity index: 1.52+/-0.20 to 1.75+/-0.31* to 1.94+/-0.34?, EF: 28+/-7 to
      34+/-7* to 38+/-8%?, *?P<0.001) in responders. No such changes were observed in
      non-responders. Furthermore, dyssynchrony diminished progressively during the
      first and the following 3 months after CRT and patients with progressive
      resynchronization experienced fewer major cardiovascular events than those
      without (P<0.001). CONCLUSION: CRT can stop the vicious cycle of remodelling and
      dyssynchrony, and actually, turn it into the virtuous cycle of reverse
      remodelling and further resynchronization.

PMID- 21865224
TI  - Substance use disorders in forensic psychiatry: differences among different types
      of offenders.
AB  - This is the first study that compared different types of offenders in forensic
      outpatient treatment (i.e., offenders of general violence [GV], intimate partner
      violence [IPV], sex crimes, and "other offenses" such as drug smuggling and
      property crimes) regarding the prevalence of substance use disorders at the time
      of the offense. In total, 35.8% of participants (n = 187) were diagnosed with any
      substance use disorder. Specifically, 61.5% of GV perpetrators, 30.9% of IPV
      perpetrators, 9.1% of sex offenders, and 26.7% of "other offenders" were
      diagnosed with substance abuse or dependence. More GV offenders and less sex
      offenders fulfilled diagnostic criteria for a substance use disorder.
      Furthermore, 29.9% of the offenders were intoxicated by substances at the moment
      they committed the offense (48.5% of GV perpetrators, 25.0% of IPV perpetrators,
      17.4% of sex offenders, and 21.0% of other offenders). More GV perpetrators were
      intoxicated during the offense. As there is a clear association between substance
      abuse and criminal behavior, substance abuse in offenders should be assessed and,
      if present, be treated.

PMID- 21865227
TI  - Altered two-dimensional strain measures of the right ventricle in patients with
      Brugada syndrome and arrhythmogenic right ventricular dysplasia/cardiomyopathy.
AB  - AIMS: Brugada syndrome (BrS) is an inherited channelopathy that can be
      characterized by mild right ventricular (RV) abnormalities that are not
      detectable with conventional echocardiography. The aim of this study was to
      evaluate the presence of RV abnormalities in BrS patients when compared with
      controls and a group of patients with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD/C) using two-dimensional (2D) strain analysis.
      METHODS AND RESULTS: We enrolled 25 BrS, 15 ARVD/C patients, and 25 controls.
      Right and left ventricular dimension and systo-diastolic function were evaluated
      by conventional echocardiography. Longitudinal systolic strain (sS) peak,
      systolic and early diastolic strain rate of lateral RV segments were evaluated by
      2D speckle tracking analysis. Left ventricle global and segmental strain measures
      were also evaluated. A reduced basal or mid-RV lateral sS were the parameters
      mostly associated with both BrS and ARVD/C. In BrS patients the minimum sS
      observed in these segments was significantly lower than that of controls (-28.9+/
      3.2% vs. -32.3+/-3.2%, P: 0.002) but significantly greater than that evaluated in
      ARVD/C patients (-24.6+/-6.7%, P<0.001 both vs. BrS and controls). No differences
      were found between the BrS and the control group when left ventricular strain
      measures were analysed. CONCLUSION: By 2D strain technique it is possible to
      observe mild abnormalities in RV systolic and diastolic function of BrS patients
      that are less pronounced than those observed in ARVD/C patients. These results
      help to better define the phenotypic characteristics of BrS patients and
      represent the basis for future studies aimed at testing their clinical usefulness
      in BrS patients.

PMID- 21865226
TI  - Predictors of mitral annulus early diastolic velocity: impact of long-axis
      function, ventricular filling pattern, and relaxation.
AB  - AIMS: Although left ventricular (LV) relaxation is well recognized as a predictor
      of mitral annulus (MA) early diastolic (E') velocity, its significance relative
      to other predictors of E' is less well understood. METHODS AND RESULTS: We
      assessed 40 healthy volunteers, 43 patients with acutely decompensated chronic
      systolic heart failure (HF), and 36 patients with hypertrophic obstructive
      cardiomyopathy (HOCM) using echocardiography and right or left heart
      catheterization. Data were obtained at baseline. In addition, in healthy
      volunteers haemodynamics were varied by graded saline infusion and low body
      negative pressure, while in HF patients it was varied by vasoactive drug
      treatment. E- and A-wave velocity (E/A) ratio of the mitral valve inflow,
      systolic MA velocity integral (s' integral) and E' and late velocity (A') of
      lateral and septal MA pulsed wave velocities were assessed by echocardiography.
      Time constant of isovolumic pressure decay tau(0)) was calculated from isovolumic
      relaxation time/[ln(aortic dicrotic notch pressure) - ln(LV filling pressure)].
      In all three groups, s' integral was the strongest predictor of E' (partial r=
      0.53-0.79; 0.81 for three groups combined), followed by E/A ratio (partial r=
      0.10-0.78; 0.26 for all groups combined) and tau(0) (partial r= -0.1 to 0.023; 
      0.21 for all groups combined). CONCLUSION: In healthy adults, patients with
      systolic HF, or patients with HOCM, E' is related to LV long-axis function and
      E/A ratio, a global marker of LV filling. E' appears less sensitive to LV
      relaxation.

PMID- 21865228
TI  - Broken arms: a three-dimensional sight closer to the Premere device.

PMID- 21865229
TI  - Acute left ventricle diastolic function improvement after transcatheter aortic
      valve implantation.
AB  - AIMS: Data regarding the effects of TAVI on LV after are scarce and conflicting
      results have been reported immediately after aortic valvuloplasty. This study
      aimed to determine the acute haemodynamic effects of transcatheter aortic valve
      implantation (TAVI) in left ventricle (LV) diastolic performance, immediately
      after aortic valvuloplasty and prosthesis deployment. METHODS AND RESULTS: Sixty
      one patients with severe aortic valve stenosis, and preserved LV systolic
      function submitted to successful TAVI, were included. All procedures were guided
      through transoesophageal echocardiography, and parameters of diastolic function
      were evaluated before and minutes after TAVI. The mean age was 83.5+/-6 years and
      mean log EuroSCORE was 18.2+/-9.4. Before the procedure, all patients presented
      LV diastolic dysfunction. Immediately after TAVI, fewer patients presented a
      restrictive pattern [27 (44.3%), before the procedure, vs. 20 (34.4%), after TAVI
      (P=0.047)], and an increase in E wave deceleration time (211.2+/-75.5 vs. 252.7+/
      102.3 cm/s, P=0.001), in E wave velocity (109.5+/-41.2 vs. 120.3+/-43.6 cm/s,
      P=0.025), and in isovolumetric relaxation time (83+/-36.5 vs. 97.1+/-36.0 ms,
      P=0.013) was observed. On multivariate analysis of covariance (ANCOVA), adjusting
      to LV systolic function, heart rate, blood pressure, and haematocrit values, the
      results remained significant. Patients referred to percutaneous approach had
      invasive haemodynamic data collected, showing a decrease in LV end-diastolic
      pressure after valve implantation [18.8+/-5.7 vs. 14.7+/-4.7, mean difference 
      4.1 (95% CI: -5.9; -2.9)]. Patients with a restrictive pattern immediately after
      TAVI presented a smaller decrease in LV end diastolic pressure (-3.3+/-4.7) than
      those with diastolic dysfunction grade I or II (-9.5+/-4.7; P=0.017). CONCLUSION:
      This is the first study describing LV diastolic performance during TAVI. Our
      results show improvement in diastolic function parameters in patients with
      preserved LV systolic function, immediately after successful TAVI.

PMID- 21865230
TI  - Intraoperative complications are more common with laparoscopic than with open
      colorectal surgery.

PMID- 21865231
TI  - Randomised trial of radical prostatectomy versus watchful waiting finds reduced
      risk for death but uncertainty still reigns.

PMID- 21865232
TI  - Laparoscopic antireflux surgery and esomeprazole similarly efficacious for
      symptoms in people with gastro-oesophageal reflux disease who respond well to
      proton pump inhibitors.

PMID- 21865233
TI  - Sustained reduction in body mass index and other cardiovascular risk markers a
      year after a 12-month intensive family-based lifestyle intervention for obese
      children; but follow-up of participants low.

PMID- 21865234
TI  - Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by
      ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes.
AB  - BACKGROUND: In mammalian follicles, oocytes are arrested at the diplotene stage
      of prophase I until meiotic resumption following the LH surge. Recently, C-type
      natriuretic peptide (CNP), encoded by natriuretic peptide precursor type C (NPPC)
      was found to suppress mouse oocyte maturation by promoting cyclic guanosine 5'
      monophospate (cGMP) production in cumulus cells. However, regulation of NPPC/CNP
      expression during the pre-ovulatory period and their regulation by the LH surge
      have not been investigated. METHODS AND RESULTS: Based on genome-wide analysis of
      DNA microarray data sets using samples from periovulatory ovaries, we found
      increases in NPPC transcripts in granulosa cells during pre-ovulatory follicle
      growth in mice and a rapid decline induced by the pre-ovulatory LH/hCG
      stimulation. Treatment of pre-ovulatory animals with hCG decreased ovarian CNP
      content. In isolated ovarian cells, NPPC mRNA was predominantly expressed in
      mural granulosa cells exhibiting similar regulation following gonadotrophin
      treatment. In cultured mouse pre-ovulatory follicles, meiosis resumption in
      oocytes by hCG treatment was accompanied by decreases in NPPC transcript levels.
      In cultured mouse cumulus cell-oocyte complexes, CNP treatment inhibited the
      resumption of meiosis with increases in cGMP levels in both cumulus cells and
      oocytes. In human ovaries, CNP levels in ovarian follicular fluid were also
      decreased following treatment of patients with an ovulatory dose of hCG.
      CONCLUSIONS: Our findings demonstrate gonadotrophins regulation of NPPC/CNP
      expression in mouse and human ovaries and confirm the role of CNP as a potent
      paracrine oocyte maturation inhibitor.

PMID- 21865235
TI  - Expression of translationally controlled tumor protein (TCTP) in the uterus of
      mice of early pregnancy and its possible significance during embryo implantation.
AB  - BACKGROUND: Translationally controlled tumor protein (TCTP) is a highly
      conserved, growth-related protein. Previous studies showed that TCTP is involved
      in many biological processes and it is essential for early embryo development and
      proliferation of embryonic stem cells. However, whether TCTP plays a role during
      embryo implantation remains unclear. This paper examines the expression and the
      role of TCTP in the uterus of mice during early pregnancy. METHODS: The
      expression of TCTP in the uterus of mice during early pregnancy was examined by
      quantitative real-time PCR, immunohistochemistry and western blot. A functional
      study of TCTP in embryo implantation of mice was also performed by intrauterine
      injection with antisense oligodeoxynucleotides (A-ODNs) of TCTP on day 3 (D3) of
      pregnancy. RESULTS: The TCTP mRNA levels were significantly upgraded from D3 to
      D5 of pregnancy and reached maximum levels on D5, then dramatically decreased on
      D6 and D7. The levels of the TCTP protein detected by western blot were
      consistent with those of the mRNA. Immunohistochemistry analysis showed that the
      TCTP protein was mainly located in the luminal and the glandular epithelium on D1
      and D2 of pregnancy and reached maximum levels on D5 in the luminal and glandular
      epithelium and in the stromal cells. The levels of TCTP in the pseudo-pregnant
      uterus of mice were lower than those of pregnant mice on D4 and D6. Furthermore,
      inhibiting the TCTP expression by intrauterine injection with A-ODNs of TCTP on
      D3 of pregnancy significantly reduced the number of the implanted embryos
      compared with the control. CONCLUSIONS: This study demonstrated that TCTP may
      play a significant role in embryo implantation in mice.

PMID- 21865236
TI  - Viral screening at the time of each donation in ART patients: is it justified?
AB  - BACKGROUND: The frequency for virology testing for couples undergoing assisted
      reproductive treatment (ART) in Europe is currently under debate, with little
      scientific data available to support the time-frame imposed by EU legislation.
      The aim of this study was to determine the incidence of blood-borne viruses (BBV)
      in this population and to assess the likelihood of seroconversion after an
      initial negative screen and the possible cost saving to couples. METHODS: We
      identified all cases where a BBV screen was performed on patients attending our
      tertiary referral unit for ART. We calculated the incidence of Hepatitis B
      surface antigen, Hepatitis C antibody and HIV infection in this population and
      the incidence of seroconversion in follow-up screening (which included Hepatitis
      B core antibody) following the implementation of the EU legislation. In all cases
      identified, we sought to assess the risk of seroconversion after an initial
      negative screen. RESULTS: Between 1998 and 2009, we identified a total of 79 291
      tests performed in over 12 500 patients. The incidence in this population of
      Hepatitis B surface antigen was 0.28% (37/12,797), Hepatitis B core antibody
      3.32% (96/2891), Hepatitis C antibody 0.33% (43/12,762) and HIV 0.007%
      (1/12,819). We were able to show that for over 6500 individuals who were tested
      and re-tested for all three viruses, no seroconversions were reported.
      CONCLUSIONS: Based on the above measured negligible risk of seroconversion after
      an initial negative screen in co-habitating couples participating in an ART
      programme, current legislation requiring screening of couples at each procurement
      of cells in the assisted reproductive setting is not clinically justified.

PMID- 21865237
TI  - The relationship between mitral regurgitation and ejection fraction as predictors
      for the prognosis of patients with heart failure.
AB  - AIMS: To study whether there is interaction between mitral regurgitation (MR) and
      left ventricular ejection fraction (LVEF) in the mortality risk of heart failure
      (HF) patients. METHODS AND RESULTS: We studied a large group of patients
      hospitalized for symptoms and clinical signs of HF in the period 2001-02. Mitral
      regurgitation was diagnosed on echocardiography and qualitatively graded as
      no/trace, mild, moderate, and severe using the colour Doppler method. Median
      follow-up time was 4.5 years. Three thousand and seventy-eight patients with HF
      were included, of whom 1890 patients (61%) had no/trace MR, 628 (20%) had mild
      MR, 452 (15%) had moderate MR, and 108 (4%) had severe MR. During follow-up, 1660
      deaths (54%) were registered. In univariate analysis, increasing severity of MR
      carried an increasing mortality risk, hazard ratio (HR) 1.10, 95% confidence
      interval (CI) 1.04-1.16, P = 0.0006 for each increasing degree of MR. In
      multivariable analysis, with adjustments made for age, sex, ejection fraction,
      serum creatinine, presence of ischaemic heart disease, chronic obstructive
      pulmonary disease, diabetes, and stroke, similar results were found, but only in
      patients with LVEF<25%, HR 1.14, 95% CI 1.03-1.26, P = 0.01 for each increasing
      degree of MR. This risk was driven by moderate and severe MR. For patients with
      LVEF>=25% the HR was 0.91, 95% CI 0.82-1.03, P = 0.2 for each increasing degree
      of MR. CONCLUSION: Mitral regurgitation has a negative effect on prognosis of
      patients with HF, but only in patients with severely reduced LVEF.

PMID- 21865238
TI  - Inhaled furosemide test in the diagnosis of acute dyspnoea.

PMID- 21865239
TI  - Evolutionary dynamics of taxonomic structure.
AB  - The distribution of species among genera and higher taxa has largely untapped
      potential to reveal among-clade variation in rates of origination and extinction.
      The probability distribution of the number of species within a genus is modelled
      with a stochastic, time-homogeneous birth-death model having two parameters: the
      rate of species extinction, MU, and the rate of genus origination, gamma, each
      scaled as a multiple of the rate of within-genus speciation, lambda. The
      distribution is more sensitive to gamma than to MU, although MU affects the size
      of the largest genera. The species : genus ratio depends strongly on both gamma
      and MU, and so is not a good diagnostic of evolutionary dynamics. The proportion
      of monotypic genera, however, depends mainly on gamma, and so may provide an
      index of the genus origination rate. Application to living marine molluscs of New
      Zealand shows that bivalves have a higher relative rate of genus origination than
      gastropods. This is supported by the analysis of palaeontological data. This
      concordance suggests that analysis of living taxonomic distributions may allow
      inference of macroevolutionary dynamics even without a fossil record.

PMID- 21865240
TI  - Defence strategies against a parasitoid wasp in Drosophila: fight or flight?
AB  - Hosts may defend themselves against parasitism through a wide variety of defence
      mechanisms, but due to finite resources, investment in one defence mechanism may
      trade-off with investment in another mechanism. We studied resistance strategies
      against the parasitoid wasp Leptopilina boulardi in two Drosophila species. We
      found that D. melanogaster had significantly lower physiological resistance
      against L. boulardi than D. simulans, and hypothesized that D. melanogaster might
      instead invest more heavily in other forms of defence, such as behavioural
      defence. We found that when given a choice between clean oviposition sites and
      sites infested with wasps, both D. melanogaster and D. simulans detected and
      avoided infested sites, which presumably limits later exposure of their offspring
      to infection. Unlike D. simulans, however, D. melanogaster laid significantly
      fewer eggs than controls in the forced presence of wasps. Our findings suggest
      that D. melanogaster relies more heavily on behavioural avoidance as defence
      against wasp parasitism than D. simulans, and that this may compensate for a lack
      of physiological defence.

PMID- 21865241
TI  - The evolutionary palaeoecology of species and the tragedy of the commons.
AB  - The fossil record presents palaeoecological patterns of rise and fall on multiple
      scales of time and biological organization. Here, we argue that the rise and fall
      of species can result from a tragedy of the commons, wherein the pursuit of self
      interests by individual agents in a larger interactive system is detrimental to
      the overall performance or condition of the system. Species evolving within
      particular communities may conform to this situation, affecting the ecological
      robustness of their communities. Results from a trophic network model of Permian
      Triassic terrestrial communities suggest that community performance on geological
      timescales may in turn constrain the evolutionary opportunities and histories of
      the species within them.

PMID- 21865242
TI  - Models in palaeontological functional analysis.
AB  - Models are a principal tool of modern science. By definition, and in practice,
      models are not literal representations of reality but provide simplifications or
      substitutes of the events, scenarios or behaviours that are being studied or
      predicted. All models make assumptions, and palaeontological models in particular
      require additional assumptions to study unobservable events in deep time. In the
      case of functional analysis, the degree of missing data associated with
      reconstructing musculoskeletal anatomy and neuronal control in extinct organisms
      has, in the eyes of some scientists, rendered detailed functional analysis of
      fossils intractable. Such a prognosis may indeed be realized if palaeontologists
      attempt to recreate elaborate biomechanical models based on missing data and
      loosely justified assumptions. Yet multiple enabling methodologies and techniques
      now exist: tools for bracketing boundaries of reality; more rigorous
      consideration of soft tissues and missing data and methods drawing on physical
      principles that all organisms must adhere to. As with many aspects of science,
      the utility of such biomechanical models depends on the questions they seek to
      address, and the accuracy and validity of the models themselves.

PMID- 21865243
TI  - Analysis and visualization of animal movement.
AB  - The interdisciplinary workshop 'Analysis and Visualization of Moving Objects' was
      held at the Lorentz Centre in Leiden, The Netherlands, from 27 June to 1 July
      2011. It brought together international specialists from ecology, computer
      science and geographical information science actively involved in the
      exploration, visualization and analysis of moving objects, such as marine
      reptiles, mammals, birds, storms, ships, cars and pedestrians. The aim was to
      share expertise, methodologies, data and common questions between different
      fields, and to work towards making significant advances in movement research. A
      data challenge based on GPS tracking of lesser black-backed gulls (Larus fuscus)
      was used to stimulate initial discussions, cross-fertilization between research
      groups and to serve as an initial focus for activities during the workshop.

PMID- 21865244
TI  - Cleaner wrasse mimics inflict higher costs on their models when they are more
      aggressive towards signal receivers.
AB  - Aggressive mimics are predatory species that resemble a 'model' species to gain
      access to food, mating opportunities or transportation at the expense of a signal
      receiver. Costs to the model may be variable, depending on the strength of the
      interaction between mimics and signal receivers. In the Indopacific, the
      bluestriped fangblenny Plagiotremus rhinorhynchos mimics juvenile cleaner wrasse
      Labroides dimidiatus. Instead of removing ectoparasites from larger coral reef
      fish, fangblennies attack fish to feed on scales and body tissue. In this study,
      juvenile cleaner wrasse suffered significant costs when associated with P.
      rhinorhynchos mimics in terms of reduced cleaning activity. Furthermore, the
      costs incurred by the model increased with heightened aggression by mimics
      towards signal receivers. This was apparently because of behavioural changes in
      signal receivers, as cleaning stations with mimics that attacked frequently were
      visited less. Variation in the costs incurred by the model may influence mimicry
      accuracy and avoidance learning by the signal receiver and thus affect the
      overall success and maintenance of the mimicry system.

PMID- 21865245
TI  - Exploring uncertainty in the calibration of the molecular clock.
AB  - Calibration is a critical step in every molecular clock analysis but it has been
      the least considered. Bayesian approaches to divergence time estimation make it
      possible to incorporate the uncertainty in the degree to which fossil evidence
      approximates the true time of divergence. We explored the impact of different
      approaches in expressing this relationship, using arthropod phylogeny as an
      example for which we established novel calibrations. We demonstrate that the
      parameters distinguishing calibration densities have a major impact upon the
      prior and posterior of the divergence times, and it is critically important that
      users evaluate the joint prior distribution of divergence times used by their
      dating programmes. We illustrate a procedure for deriving calibration densities
      in Bayesian divergence dating through the use of soft maximum constraints.

PMID- 21865246
TI  - Incubation temperature affects multiple measures of immunocompetence in young
      wood ducks (Aix Sponsa).
AB  - Parental effects play a vital role in shaping offspring phenotype. In birds,
      incubation behaviour is a critical parental effect because it influences the
      early developmental environment and can therefore have lifelong consequences for
      offspring phenotype. Recent studies that manipulated incubation temperature found
      effects on hatchling body composition, condition and growth, suggesting that
      incubation temperature could also affect energetically costly physiological
      processes of young birds that are important to survival (e.g. immune responses).
      We artificially incubated wood duck (Aix sponsa) eggs at three biologically
      relevant temperatures. Following incubation, we used two immunoassays to measure
      acquired immune responses of ducklings. Ducklings incubated at the lowest
      temperature had reduced growth, body condition and responses to both of our
      immune challenges, compared with those from the higher temperatures. Our results
      show that incubation temperatures can be an important driver of phenotypic
      variation in avian populations.

PMID- 21865247
TI  - Pre-fledgling oxidative damage predicts recruitment in a long-lived bird.
AB  - Empirical evidence has shown that stressful conditions experienced during
      development may exert long-term negative effects on life-history traits. Although
      it has been suggested that oxidative stress has long-term effects, little is
      known about delayed consequences of oxidative stress experienced early in life in
      fitness-related traits. Here, we tested whether oxidative stress during
      development has long-term effects on a life-history trait directly related to
      fitness in three colonies of European shags Phalacrocorax aristotelis. Our
      results revealed that recruitment probability decreased with oxidative damage
      during the nestling period; oxidative damage, in turn, was related to the level
      of antioxidant capacity. Our results suggest a link between oxidative stress
      during development and survival to adulthood, a key element of population
      dynamics.

PMID- 21865248
TI  - Staining diatoms with rhodamine dyes: control of emission colour in photonic
      biocomposites.
AB  - The incorporation of rhodamine dyes in the cell wall of diatoms Coscinodiscus
      granii and Coscinodiscus wailesii for the production of luminescent hybrid
      nanostructures is investigated. By systematic variation of the substitution
      pattern of the rhodamine core, we found that carbonic acids are considerably
      better suited than esters because of their physiological compatibility. The amino
      substitution pattern that controls the optical properties of the chromophore has
      no critical influence on dye uptake and incorporation, thus a variety of
      biocomposites with different emission maxima can be prepared. Applications in
      biomineralization studies as well as in materials science are envisioned.

PMID- 21865249
TI  - On the role of DNA biomechanics in the regulation of gene expression.
AB  - DNA is traditionally seen as a linear sequence of instructions for cellular
      functions that are expressed through biochemical processes. Cellular DNA,
      however, is also organized as a complex hierarchical structure with a mosaic of
      mechanical features, and a growing body of evidence is now emerging to imply that
      these mechanical features are connected to genetic function. Mechanical tension,
      for instance, which must be felt by DNA within the heavily constrained and
      continually fluctuating cellular environment, can affect a number of regulatory
      processes implicating a role for biomechanics in gene expression complementary to
      that of biochemical regulation. In this article, we review evidence for such
      mechanical pathways of genetic regulation.

PMID- 21865250
TI  - Direct evidence of phospholipids in gecko footprints and spatula-substrate
      contact interface detected using surface-sensitive spectroscopy.
AB  - Observers ranging from Aristotle to young children have long marvelled at the
      ability of geckos to cling to walls and ceilings. Detailed studies have revealed
      that geckos are 'sticky' without the use of glue or suction devices. Instead, a
      gecko's stickiness derives from van der Waals interactions between proteinaceous
      hairs called setae and substrate. Here, we present surprising evidence that
      although geckos do not use glue, a residue is transferred on surfaces as they
      walk-geckos leave footprints. Using matrix-free nano-assisted laser desorption
      ionization mass spectrometry, we identified the residue as phospholipids with
      phosphocholine head groups. Moreover, interface-sensitive sum-frequency
      generation spectroscopy revealed predominantly hydrophobic methyl and methylene
      groups and the complete absence of water at the contact interface between a gecko
      toe pad and the substrate. The presence of lipids has never been considered in
      current models of gecko adhesion. Our analysis of gecko footprints and the toe
      pad-substrate interface has significant consequences for models of gecko adhesion
      and by extension, the design of synthetic mimics.

PMID- 21865251
TI  - Nanostructural self-assembly of iridescent feather barbules through depletion
      attraction of melanosomes during keratinization.
AB  - Avian plumage colours are model traits in understanding the evolution of sexually
      selected ornamental traits. Paradoxically, iridescent structural colours,
      probably the most dazzling of these traits, remain the most poorly understood.
      Though some data suggest that expression of bright iridescent plumage colours
      produced by highly ordered arrays of melanosomes and keratin is condition
      dependent, almost nothing is known of their ontogeny and thus of any
      developmental mechanisms that may be susceptible to perturbation. Here, we use
      light and electron microscopy to compare the ontogeny of iridescent male and non
      iridescent female feathers in blue-black grassquits. Feather barbules of males
      contain a single layer of melanosomes bounded by a thin layer of keratin
      producing blue iridescent colour, while those of females contain disorganized
      melanosomes and no outer layer. We found that nanostructural organization of male
      barbules occurs late in development, following death of the barbule cell, and is
      thus unlikely to be under direct cellular control, contrary to previous
      suggestions. Rather, organization appears to be caused by entropically driven
      self-assembly through depletion attraction forces that pin melanosomes to the
      edge of barbule cells and to one another. These forces are probably stronger in
      developing barbules of males than of females because their melanosomes are (i)
      larger, (ii) more densely packed, and (iii) more homogeneously distributed owing
      to the more consistent shape of barbules during keratinization. These data
      provide the first proposed developmental pathway for iridescent plumage colours,
      and suggest that any condition dependence of iridescent barbules is likely driven
      by factors other than direct metabolic cost.

PMID- 21865252
TI  - Tilted cellulose arrangement as a novel mechanism for hygroscopic coiling in the
      stork's bill awn.
AB  - The sessile nature of plants demands the development of seed-dispersal mechanisms
      to establish new growing loci. Dispersal strategies of many species involve
      drying of the dispersal unit, which induces directed contraction and movement
      based on changing environmental humidity. The majority of researched hygroscopic
      dispersal mechanisms are based on a bilayered structure. Here, we investigate the
      motility of the stork's bill (Erodium) seeds that relies on the tightening and
      loosening of a helical awn to propel itself across the surface into a safe
      germination place. We show that this movement is based on a specialized single
      layer consisting of a mechanically uniform tissue. A cell wall structure with
      cellulose microfibrils arranged in an unusually tilted helix causes each cell to
      spiral. These cells generate a macroscopic coil by spiralling collectively. A
      simple model made from a thread embedded in an isotropic foam matrix shows that
      this cellulose arrangement is indeed sufficient to induce the spiralling of the
      cells.

PMID- 21865253
TI  - The global spread of drug-resistant influenza.
AB  - Resistance to oseltamivir, the most widely used influenza antiviral drug, spread
      to fixation in seasonal influenza A(H1N1) between 2006 and 2009. This sudden rise
      in resistance seemed puzzling given the low overall level of the oseltamivir
      usage and the lack of a correlation between local rates of resistance and
      oseltamivir usage. We used a stochastic simulation model and deterministic
      approximations to examine how such events can occur, and in particular to
      determine how the rate of fixation of the resistant strain depends both on its
      fitness in untreated hosts as well as the frequency of antiviral treatment. We
      found that, for the levels of antiviral usage in the population, the resistant
      strain will eventually spread to fixation, if it is not attenuated in
      transmissibility relative to the drug-sensitive strain, but not at the speed
      observed in seasonal H1N1. The extreme speed with which the resistance spread in
      seasonal H1N1 suggests that the resistant strain had a transmission advantage in
      untreated hosts, and this could have arisen from genetic hitchhiking, or from the
      mutations responsible for resistance and compensation. Importantly, our model
      also shows that resistant virus will fail to spread if it is even slightly less
      transmissible than its sensitive counterpart--a finding of relevance given that
      resistant pandemic influenza (H1N1) 2009 may currently suffer from a small, but
      nonetheless experimentally perceptible reduction in transmissibility.

PMID- 21865254
TI  - Emergence of coherent structures and large-scale flows in motile suspensions.
AB  - The emergence of coherent structures, large-scale flows and correlated dynamics
      in suspensions of motile particles such as swimming micro-organisms or artificial
      microswimmers is studied using direct particle simulations. A detailed model is
      proposed for a slender rod-like particle that propels itself in a viscous fluid
      by exerting a prescribed tangential stress on its surface, and a method is
      devised for the efficient calculation of hydrodynamic interactions in large-scale
      suspensions of such particles using slender-body theory and a smooth particle
      mesh Ewald algorithm. Simulations are performed with periodic boundary conditions
      for various system sizes and suspension volume fractions, and demonstrate a
      transition to large-scale correlated motions in suspensions of rear-actuated
      swimmers, or Pushers, above a critical volume fraction or system size. This
      transition, which is not observed in suspensions of head-actuated swimmers, or
      Pullers, is seen most clearly in particle velocity and passive tracer statistics.
      These observations are consistent with predictions from our previous mean-field
      kinetic theory, one of which states that instabilities will arise in uniform
      isotropic suspensions of Pushers when the product of the linear system size with
      the suspension volume fraction exceeds a given threshold. We also find that the
      collective dynamics of Pushers result in giant number fluctuations, local
      alignment of swimmers and strongly mixing flows. Suspensions of Pullers, which
      evince no large-scale dynamics, nonetheless display interesting deviations from
      the random isotropic state.

PMID- 21865256
TI  - Manipulating individual state during migration provides evidence for carry-over
      effects modulated by environmental conditions.
AB  - Despite observational evidence of carry-over effects (COEs, events occurring in
      one season that produce residual effects on individuals the following seasons),
      to our knowledge no experimental studies have been carried out to explore how
      COEs might affect reproductive output. We simulated an environmental perturbation
      affecting spring-staging migrants to investigate COEs in greater snow geese
      (Anser caerulescens atlanticus). During three consecutive years, 2037 females
      captured during spring staging (approx. 3000 km south of their Arctic breeding
      grounds) were maintained in captivity (with or without access to food) for 0-4
      days. Duration of captivity (but not food treatment) negatively affected
      reproductive success, probably through stress response. Reproductive success was
      reduced by 45-71% in 2 years, but not in a third year with unusually favourable
      breeding conditions. This unprecedented manipulation indicates that COEs can have
      a strong effect on individual reproductive success in long-distance migrants, but
      that this effect can be partly compensated for by good environmental conditions
      on the breeding ground.

PMID- 21865255
TI  - Cryoprotection-lyophilization and physical stabilization of rifampicin-loaded
      flower-like polymeric micelles.
AB  - Rifampicin-loaded poly(epsilon-caprolactone)-b-poly(ethylene glycol)-poly(epsilon
      caprolactone) flower-like polymeric micelles display low aqueous physical
      stability over time and undergo substantial secondary aggregation. To improve
      their physical stability, the lyoprotection-lyophilization process was thoroughly
      characterized. The preliminary cryoprotectant performance of mono- and
      disaccharides (e.g. maltose, glucose), hydroxypropyl-beta-cyclodextrin (HPbetaCD)
      and poly(ethylene glycol) (PEG) of different molecular weights was assessed in
      freeze-thawing assays at -20 degrees C, -80 degrees C and -196 degrees C. The
      size and size distribution of the micelles at the different stages were measured
      by dynamic light scattering (DLS). A cryoprotectant factor (f(c)) was determined
      by taking the ratio between the size immediately after the addition of the
      cryoprotectant and the size after the preliminary freeze-thawing assay. The
      benefit of a synergistic cryoprotection by means of saccharide/PEG mixtures was
      also assessed. Glucose (1 : 20), maltose (1 : 20), HPbetaCD (1 : 5) and glucose
      or maltose mixtures with PEG3350 (1 : 20) (copolymer:cryoprotectant weight ratio)
      were the most effective systems to protect 1 per cent micellar systems.
      Conversely, only HPbetaCD (1 : 5) cryoprotected more concentrated drug-loaded
      micelles (4% and 6%). Then, those micelle/cryoprotectant systems that displayed
      f(c) values smaller than 2 were freeze-dried. The morphology of freeze-dried
      powders was characterized by scanning electron microscopy and atomic force
      microscopy and the residual water content analysed by the Karl Fisher method. The
      HPbetaCD-added lyophilisates were brittle porous cakes (residual water was
      between 0.8% and 3%), easily redispersable in water to form transparent systems
      with a minimal increase in the micellar size, as determined by DLS.

PMID- 21865258
TI  - The peopling of Europe and the cautionary tale of Y chromosome lineage R-M269.
AB  - Recently, the debate on the origins of the major European Y chromosome haplogroup
      R1b1b2-M269 has reignited, and opinion has moved away from Palaeolithic origins
      to the notion of a younger Neolithic spread of these chromosomes from the Near
      East. Here, we address this debate by investigating frequency patterns and
      diversity in the largest collection of R1b1b2-M269 chromosomes yet assembled. Our
      analysis reveals no geographical trends in diversity, in contradiction to
      expectation under the Neolithic hypothesis, and suggests an alternative
      explanation for the apparent cline in diversity recently described. We further
      investigate the young, STR-based time to the most recent common ancestor
      estimates proposed so far for R-M269-related lineages and find evidence for an
      appreciable effect of microsatellite choice on age estimates. As a consequence,
      the existing data and tools are insufficient to make credible estimates for the
      age of this haplogroup, and conclusions about the timing of its origin and
      dispersal should be viewed with a large degree of caution.

PMID- 21865259
TI  - Mental health of young adult patients who do not attend appointments in primary
      care: a retrospective cohort study.
AB  - OBJECTIVE: The objective is to examine the relation between young adults' non
      attendance at primary care appointments and mental health problems, using a
      retrospective cohort study, in a urban primary health care facility in a
      relatively deprived and ethnically diverse area of Oxford, England. METHODS: Two
      hundred and nine patients aged between 15 and 35 years who failed to attend a
      doctor's appointment in primary care during 2008 each matched with two control
      patients of the same age and gender who had attended appointments during the same
      period. Main outcome measure is the presentation with a mental health problem
      within 12 months following the missed appointment. RESULTS: Non-attendance in
      primary care among 15-35 year olds was strongly associated with presentation of
      mental health problems. Those who did not attend an appointment were more likely
      to have presented mental health problems in the past [31.0% versus 8.9%, odds
      ratio (OR) 4.72, 95% confidence interval (CI) 3.00-7.42] and to present mental
      health problems within the ensuing 12 months (32.0% versus 7.4%, OR 5.91, 95% CI
      3.69-9.46) when compared with those who attended appointments. Patients with no
      known past history of mental health problems were more likely to make their first
      recorded mental health presentation in the 12 months following a non-attendance
      when compared with those who attended (10.3% versus 3.1%, OR 3.60, 95% CI 1.76
      7.35). CONCLUSIONS: Non-attendance of a young adult for a doctor's appointment in
      primary care may signal a mental health problem. This applies whether or not the
      patient is known to have presented mental health problems in the past.

PMID- 21865257
TI  - Reactive oxygen species production and discontinuous gas exchange in insects.
AB  - While biochemical mechanisms are typically used by animals to reduce oxidative
      damage, insects are suspected to employ a higher organizational level,
      discontinuous gas exchange mechanism to do so. Using a combination of real-time,
      flow-through respirometry and live-cell fluorescence microscopy, we show that
      spiracular control associated with the discontinuous gas exchange cycle (DGC) in
      Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails
      to increase mean ROS production, although minima are elevated above normoxic
      levels. Furthermore, a negative relationship between mean   and mean ROS
      production indicates that higher ROS production is generally associated with
      lower  . Our results, therefore, suggest a possible signalling role for ROS in
      DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by
      regulating ROS production.

PMID- 21865260
TI  - Hormonal contraception and risk of cancer.

PMID- 21865261
TI  - Histone modifications and methyl-CpG-binding domain protein levels at the TNFSF7
      (CD70) promoter in SLE CD4+ T cells.
AB  - In systemic lupus erythematosus (SLE), T lymphocytes overexpress CD70 (TNFSF7
      gene), leading to the synthesis of autoreactive IgGs. CD70 upregulation in SLE
      CD4(+) T cells is associated with hypomethylation of TNFSF7 promoter. In this
      study, we explored histone modifications in the TNFSF7 promoter region in SLE
      CD4(+) T cells, and characterized the effects of a DNA methyltransferase
      inhibitor (5-azaC) and a histone deacetylase inhibitor (TSA) on CD70 expression.
      We found that CD70 mRNA was significantly increased in active lupus CD4(+) T
      cells, and in control cells treated with 5-azaC, TSA, or both. Histone H3
      acetylation and dimethylated H3 lysine 4 (H3K4me2) levels were significantly
      elevated in patients with lupus, and both factors correlated positively with
      disease activity. MeCP2 protein levels within the TNFSF7 promoter decreased in
      patients with active lupus. Treatment of CD4+ T cells with 5-azaC alone
      significantly raised H3K4 dimethyl levels at the TNFSF7 locus. TSA treatment
      significantly increased H3 and H4 acetylation levels, as well as levels of H3K4
      dimethylation at the TNFSF7 locus. Treatment with 5-azaC plus TSA enhanced H3
      acetylation levels. These findings indicate that aberrant histone modifications
      within the TNFSF7 promoter may contribute to the development of lupus by
      increasing CD70 expression in CD4(+) T cells.

PMID- 21865262
TI  - Differential interaction of dicarboxylates with human sodium-dicarboxylate
      cotransporter 3 and organic anion transporters 1 and 3.
AB  - Organic anions are taken up from the blood into proximal tubule cells by organic
      anion transporters 1 and 3 (OAT1 and OAT3) in exchange for dicarboxylates. The
      released dicarboxylates are recycled by the sodium dicarboxylate cotransporter 3
      (NaDC3). In this study, we tested the substrate specificities of human NaDC3,
      OAT1, and OAT3 to identify those dicarboxylates for which the three cooperating
      transporters have common high affinities. All transporters were stably expressed
      in HEK293 cells, and extracellularly added dicarboxylates were used as inhibitors
      of [(14)C]succinate (NaDC3), p-[(3)H]aminohippurate (OAT1), or [(3)H]estrone-3
      sulfate (OAT3) uptake. Human NaDC3 was stably expressed as proven by
      immunochemical methods and by sodium-dependent uptake of succinate (K(0.5) for
      sodium activation, 44.6 mM; Hill coefficient, 2.1; K(m) for succinate, 18 MUM).
      NaDC3 was best inhibited by succinate (IC(50) 25.5 MUM) and less by alpha
      ketoglutarate (IC(50) 69.2 MUM) and fumarate (IC(50) 95.2 MUM). Dicarboxylates
      with longer carbon backbones (adipate, pimelate, suberate) had low or no affinity
      for NaDC3. OAT1 exhibited the highest affinity for glutarate, alpha
      ketoglutarate, and adipate (IC(50) between 3.3 and 6.2 MUM), followed by pimelate
      (18.6 MUM) and suberate (19.3 MUM). The affinity of OAT1 to succinate and
      fumarate was low. OAT3 showed the same dicarboxylate selectivity with ~13-fold
      higher IC(50) values compared with OAT1. The data 1) reveal alpha-ketoglutarate
      as a common high-affinity substrate of NaDC3, OAT1, and OAT3 and 2) suggest
      potentially similar molecular structures of the binding sites in OAT1 and OAT3
      for dicarboxylates.

PMID- 21865263
TI  - Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic
      calcification in a rat model of cystic renal disease.
AB  - The effect of angiotensin-converting enzyme inhibition on function and structure
      of the aorta was studied in the Lewis polycystic kidney (LPK) rat model of cystic
      renal disease and Lewis controls. Pulse-wave velocity (PWV) was recorded under
      urethane anesthesia (1.3 g/kg ip) in mixed-sex animals aged 6 and 12 wk and in 12
      wk-old animals treated with perindopril (3 mg.kg(-1).day(-1) po) from age 6-12
      wk. Tail-cuff systolic pressures were recorded over the treatment period. After
      PWV measurements, animals were euthanized and the aorta was removed for
      histomorphological and calcium analysis. Hypertension in LPK at 6 and 12 wk was
      associated with a shift of the PWV curve upward and to the right, indicating a
      decrease in aortic compliance, which was significantly reduced by perindopril.
      LPK demonstrated greater aortic calcification (6 wk: 123 +/- 19 vs. 65 +/- 7 and
      12 wk: 406 +/- 6 vs. 67 +/- 6 MUmol/g, P < 0.001, LPK vs. Lewis, respectively).
      This was reduced by treatment with perindopril (172 +/- 48 MUmol/g, 12 wk LPK P <
      0.001). Medial cross-sectional area and elastic modulus/wall stress of the aorta
      were greater in LPK vs. Lewis control animals at 6 and 12 wk of age and showed an
      age-related increase that was prevented by treatment with perindopril (P <
      0.001). Perindopril also ameliorated the degradation of elastin, increase in
      collagen content, and medial elastocalcinosis seen in 12-wk LPK. Overall,
      perindopril improved the structural and functional indices of aortic stiffness in
      the LPK rats, demonstrating a capacity for angiotensin-converting enzyme
      inhibition to limit vascular remodeling in chronic kidney disease.

PMID- 21865264
TI  - Increased renin excretion is associated with augmented urinary angiotensin II
      levels in chronic angiotensin II-infused hypertensive rats.
AB  - Renin expression in principal cells of collecting ducts (CD) is upregulated in
      angiotensin II (ANG II)-dependent hypertensive rats; however, it remains unclear
      whether increased CD-derived renin undergoes tubular secretion. Accordingly,
      urinary levels of renin (uRen), angiotensinogen (uAGT), and ANG II (uANG II) were
      measured in chronic ANG II-infused Sprague-Dawley rats (80 ng/min for 14 days, n
      = 10) and sham-operated rats (n = 10). Systolic blood pressure increased in the
      ANG II rats by day 5 and continued to increase throughout the study (day 13; ANG
      II: 175 +/- 10 vs. sham: 116 +/- 2 mmHg; P < 0.05). ANG II infusion increased
      renal cortical and medullary ANG II levels (cortical ANG II: 606 +/- 72 vs. 247
      +/- 43 fmol/g; P < 0.05; medullary ANG II: 2,066 +/- 116 vs. 646 +/- 36 fmol/g; P
      < 0.05). Although plasma renin activity (PRA) was suppressed in the ANG II
      infused rats (0.3 +/- 0.2 vs. 5.5 +/- 1.8 ng ANG I.ml(-1).h(-1); P < 0.05), renin
      content in renal medulla was increased (12,605 +/- 1,343 vs. 7,956 +/- 765 ng ANG
      I.h(-1).mg(-1); P < 0.05). Excretion of uAGT and uANG II increased in the ANG II
      rats [uAGT: 1,107 +/- 106 vs. 60 +/- 26 ng/day; P < 0.0001; uANG II: 3,813 +/-
      431 vs. 2,080 +/- 361 fmol/day; P < 0.05]. By day 13, despite suppression of PRA,
      urinary prorenin content increased in ANG II rats [15.7 +/- 3 vs. 2.6 +/- 1 * 10(
      3) enzyme units excreted (EUE)/day, P < 0.01] as was the excretion rate of renin
      (8.6 +/- 2 * 10(-6) EUE/day) compared with sham (2.8 +/- 1 * 10(-6) EUE/day; P <
      0.05). Urinary renin and prorenin protein levels examined by Western blot were
      augmented ~10-fold in the ANG II-infused rats. Concomitant AT(1) receptor
      blockade with candesartan prevented the increase. Thus, in ANG II-dependent
      hypertensive rats with marked PRA suppression, increased urinary levels of renin
      and prorenin reflect their augmented secretion by CD cells into the luminal
      fluid. The greater availability of renin and AGT in the urine reflects the
      capability for intratubular ANG II formation which stimulates sodium reabsorption
      in distal nephron segments.

PMID- 21865265
TI  - Angiotensin receptor blockers shift the circadian rhythm of blood pressure by
      suppressing tubular sodium reabsorption.
AB  - Recently, we found that an angiotensin II receptor blocker (ARB) restored the
      circadian rhythm of the blood pressure (BP) from a nondipper to a dipper pattern,
      similar to that achieved with sodium intake restriction and diuretics (Fukuda M,
      Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S, Nishio T, Yoshida A,
      Kimura G. J Hypertens 26: 583-588, 2008). ARB enhanced natriuresis during the
      day, while BP was markedly lower during the night, resulting in the dipper
      pattern. In the present study, we examined whether the suppression of tubular
      sodium reabsorption, similar to the action of diuretics, was the mechanism by
      which ARB normalized the circadian BP rhythm. BP and glomerulotubular balance
      were compared in 41 patients with chronic kidney disease before and during ARB
      treatment with olmesartan once a day in the morning for 8 wk. ARB increased
      natriuresis (sodium excretion rate; U(Na)V) during the day (4.5 +/- 2.2 to 5.5 +/
      2.1 mmol/h, P = 0.002), while it had no effect during the night (4.3 +/- 2.0 to
      3.8 +/- 1.6 mmol/h, P = 0.1). The night/day ratios of both BP and U(Na)V were
      decreased. The decrease in the night/day ratio of BP correlated with the increase
      in the daytime U(Na)V (r = 0.42, P = 0.006). Throughout the whole day, the
      glomerular filtration rate (P = 0.0006) and tubular sodium reabsorption (P =
      0.0005) were both reduced significantly by ARB, although U(Na)V remained constant
      (107 +/- 45 vs. 118 +/- 36 mmol/day, P = 0.07). These findings indicate that the
      suppression of tubular sodium reabsorption, showing a resemblance to the action
      of diuretics, is the primary mechanism by which ARB can shift the circadian BP
      rhythm into a dipper pattern.

PMID- 21865266
TI  - Urinary C-type natriuretic peptide excretion: a potential novel biomarker for
      renal fibrosis during aging.
AB  - Renal aging is characterized by structural changes in the kidney including
      fibrosis, which contributes to the increased risk of kidney and cardiac failure
      in the elderly. Studies involving healthy kidney donors demonstrated subclinical
      age-related nephropathy on renal biopsy that was not detected by standard
      diagnostic tests. Thus there is a high-priority need for novel noninvasive
      biomarkers to detect the presence of preclinical age-associated renal structural
      and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective
      properties and is present in the kidney; however, its modulation during aging
      remains undefined. We assessed circulating and urinary CNP in a Fischer rat model
      of experimental aging and also determined renal structural and functional
      adaptations to the aging process. Histological and electron microscopic analysis
      demonstrated significant renal fibrosis, glomerular basement membrane thickening,
      and mesangial matrix expansion with aging. While plasma CNP levels progressively
      declined with aging, urinary CNP excretion increased, along with the ratio of
      urinary to plasma CNP, which preceded significant elevations in proteinuria and
      blood pressure. Also, CNP immunoreactivity was increased in the distal and
      proximal tubules in both the aging rat and aging human kidneys. Our findings
      provide evidence that urinary CNP and its ratio to plasma CNP may represent a
      novel biomarker for early age-mediated renal structural alterations, particularly
      fibrosis. Thus urinary CNP could potentially aid in identifying subjects with
      preclinical structural changes before the onset of symptoms and disease, allowing
      for the initiation of strategies designed to prevent the progression of chronic
      kidney disease particularly in the aging population.

PMID- 21865267
TI  - Expression of SIRT1 in gastric cardiac cancer and its clinicopathologic
      significance.
AB  - SIRT1 is a deacetylase that modifies gene expression. Some researchers have found
      that SIRT1 is upregulated in malignant tumor tissues. Therefore, this study
      investigated the SIRT1 expression in gastric cardiac carcinoma and its
      correlation with clinicopathologic features and prognosis. Tissue microarray
      technique and immunohistochemical stains were used to detect the expression of
      SIRT1, p53, and Ki-67 in 176 gastric cardiac carcinoma tissues and 32 normal
      gastric cardiac region tissues. SIRT1 expression in gastric cardiac carcinoma was
      significantly higher than that in normal gastric cardiac tissues and was
      associated with lymphatic metastasis, TNM stage, survival rate and mean survival
      time. Expression of Ki-67 in the SIRT1 positive group was significantly higher
      than that in the negative group. In conclusion, high expression of SIRT1 in
      gastric cardiac carcinoma was correlated with lymphatic metastasis, TNM stage,
      proliferative status and prognosis. SIRT1 might be a biological parameter to
      evaluate malignant degree and prognosis of gastric cardiac carcinoma.

PMID- 21865268
TI  - Metaplastic carcinoma of the breast with dominant squamous and sebaceous
      differentiation in the primary tumor and osteochondroid metaplasia in a distant
      metastasis: report of a case with review of sebaceous differentiation in breast
      tumors.
AB  - Metaplastic breast carcinoma is an uncommon tumor that develops from conventional
      ductal mammary carcinoma, usually consisting of squamous and/or spindle cell
      components and/or mesenchymal elements. Although several morphological subtypes
      of metaplastic breast carcinoma are known, sebaceous metaplasia has not yet been
      described in this context. The authors report a case of an 84-year-old woman with
      a huge, ulcerated primary tumor in her left breast that had already been present
      for 10 years. Pulmonary and bone metastases and a tumor nodule in the
      contralateral breast were also detected at the time of admission. Left simple
      mastectomy was performed. Histological examination of the tumor revealed
      metaplastic carcinoma consisting of ductal carcinoma, which immunohistochemically
      exhibited a triple-negative immunoprofile, along with dominant areas of squamous
      and sebaceous differentiation. Adjuvant chemotherapy was subsequently given with
      partial regression of the systemic metastases. Seven months after surgery and
      diagnosis, a new, rapidly growing, large soft tissue metastatic tumor appeared in
      the intramuscular compartment of the patient's right thigh, which was removed and
      histologically examined. Morphologically this metastatic tumor showed ductal
      adenocarcinoma along with areas of sebaceous differentiation and, in addition,
      osteochondroid metaplasia. Immunohistochemically, unlike the primary, this tumor
      expressed HER-2. The case is presented because of its rarity, and sebaceous
      differentiation is also proposed as a novel type of metaplasia in this context,
      expanding the spectrum of the histological patterns of metaplastic breast
      carcinoma. The literature concerning breast sebaceous lesions is reviewed, and
      the hypothetical biological mechanisms responsible for the tumor pathogenesis in
      this case are discussed.

PMID- 21865269
TI  - Using proportion of similar response to evaluate correlates of protection for
      vaccine efficacy.
AB  - A question of interest in many vaccine clinical development programmes is whether
      vaccine-induced serum antibody level can be used as a correlate of vaccine
      efficacy; that is, whether serum antibody levels induced by a candidate vaccine
      can reliably predict the risk of breakthrough disease. Traditionally, analyses to
      answer this question have been based on modelling the incidence of breakthrough
      disease as a function of antibody level, among vaccinated subjects in clinical
      trials. The Proportion of Similar Response (PSR) method will be described and
      explored, and compared to the Receive Operator Characteristics (ROC) curve as a
      graphical tool and the area under the ROC (AUROC) as a summary measure in the
      context of evaluating correlates of protection. A way to use PSR analysis as
      complementary to Youden's index as a simple and elegant method to determine the
      discriminatory ability of a test and to set an optimal threshold value will be
      presented. In addition, the relationships among PSR and other measures of overlap
      and discrimination will be described. An example based on a clinical trial from a
      development programme for a vaccine against human papillomavirus (HPV) will be
      presented. 

PMID- 21865270
TI  - Measuring continuous baseline covariate imbalances in clinical trial data.
AB  - This paper presents and compares several methods of measuring continuous baseline
      covariate imbalance in clinical trial data. Simulations illustrate that though
      the t-test is an inappropriate method of assessing continuous baseline covariate
      imbalance, the test statistic itself is a robust measure in capturing imbalance
      in continuous covariate distributions. Guidelines to assess effects of imbalance
      on bias, type I error rate and power for hypothesis test for treatment effect on
      continuous outcomes are presented, and the benefit of covariate-adjusted analysis
      (ANCOVA) is also illustrated. 

PMID- 21865271
TI  - Is your mum on drugs?

PMID- 21865272
TI  - HIV groups call on US government to fund preventive drug treatment.

PMID- 21865273
TI  - Government is still "listening" as NHS Future Forum continues work.

PMID- 21865274
TI  - Hypertension diagnosis should be based on ambulatory blood pressure monitoring,
      NICE recommends.

PMID- 21865275
TI  - Computational design of synthetic regulatory networks from a genetic library to
      characterize the designability of dynamical behaviors.
AB  - The engineering of synthetic gene networks has mostly relied on the assembly of
      few characterized regulatory elements using rational design principles. It is of
      outmost importance to analyze the scalability and limits of such a design
      workflow. To analyze the design capabilities of libraries of regulatory elements,
      we have developed the first automated design approach that combines such elements
      to search the genotype space associated to a given phenotypic behavior. Herein,
      we calculated the designability of dynamical functions obtained from circuits
      assembled with a given genetic library. By designing circuits working as
      amplitude filters, pulse counters and oscillators, we could infer new mechanisms
      for such behaviors. We also highlighted the hierarchical design and the
      optimization of the interface between devices. We dissected the functional
      diversity of a constrained library and we found that even such libraries can
      provide a rich variety of behaviors. We also found that intrinsic noise slightly
      reduces the designability of digital circuits, but it increases the designability
      of oscillators. Finally, we analyzed the robust design as a strategy to
      counteract the evolvability and noise in gene expression of the engineered
      circuits within a cellular background, obtaining mechanisms for robustness
      through non-linear negative feedback loops.

PMID- 21865276
TI  - Drinks industry is using social networking to promote alcohol to young people,
      report warns.

PMID- 21865277
TI  - Private finance initiatives to build hospitals do not provide value for money,
      English MPs warn.

PMID- 21865278
TI  - Health inequalities and cystic fibrosis.

PMID- 21865279
TI  - Will industry influence derail UN summit?

PMID- 21865280
TI  - Commentary: UN high level meeting on non-communicable diseases: an opportunity
      for whom?

PMID- 21865281
TI  - Risk of infections in rheumatoid arthritis patients treated with tocilizumab.
AB  - OBJECTIVES: To investigate the occurrence and risk factors for infections in RA
      patients treated with tocilizumab. METHODS: A cohort of all RA patients (n = 112)
      starting tocilizumab therapy between October 2008 and March 2010 in Northern
      Bavaria was screened for infections. Mild/moderate and severe infections were
      recorded. Multivariate logistic regression analysis was used to define risk
      factors for infection. RESULTS: Overall, 26 patients developed infections [23.2%;
      58.0/100 patient-years (py)], 18 of them were mild to moderate (16.1%, 40.1/100
      py) and 8 were severe (17.9/100 py). Concomitant use of LEF and prednisone, high
      disease activity and previous therapy with rituximab were associated with the
      occurrence of mild/moderate infections. Severe infections were related to longer
      disease duration, exposure to more than three previous DMARDs and concomitant
      therapy with proton-pump inhibitors. CONCLUSION: The rate of infection in RA
      patients treated with tocilizumab in clinical practice is higher than in the
      clinical trial populations. Increased attention should especially be given to
      patients with longer disease duration, previous exposure to multiple DMARDs, i.e.
      previous exposure to rituximab and those receiving concomitant LEF, prednisone or
      proton-pump inhibitor treatment.

PMID- 21865282
TI  - Rheumatic disorders affecting the head and neck: underestimated diseases.
AB  - OBJECTIVES: To describe the clinical manifestations of rheumatic disorders with
      isolated head and neck (H&N) affection and to introduce a novel diagnostic
      pathway. METHODS: From 2004 to 2010, 90 patients presented with isolated H&N
      symptoms of a rheumatic disorder were included in the study. Rheumatic disorders
      were classified according to the ACR criteria. In 2008, we introduced a novel
      diagnostic pathway to reduce under-diagnosis of primary rheumatic disorders in
      the H&N. Disease-related data were assessed retrospectively and set into clinical
      context. RESULTS: The majority of patients suffered from SS (n = 42),
      granulomatosis with polyangiitis (Wegener's) (n = 13) and sarcoidosis (n = 18)
      with predominance for female patients (n = 65). Enlargement of the major salivary
      glands (n = 47), sicca symptoms (n = 41) and cervical lymphadenopathy (n = 25)
      represented the most frequent symptoms. Interestingly, 3% of all enlargements of
      salivary glands and 4% of all cervical lymphadenopathy could be contributed to
      rheumatic disorders. The mean time to diagnosis was 20.71 months for SS, 8.4
      months for granulomatosis with polyangiitis and 57.5 months for sarcoidosis.
      After implementation of the newly developed diagnostic pathway in 2008, the
      annually diagnosed rheumatic disorders increased 5-fold. CONCLUSIONS: The
      majority of rheumatic diseases of the H&N can be related to SS, granulomatosis
      with polyangiitis and sarcoidosis. However, the lack of specific symptoms and the
      clinical variability of H&N manifestation may contribute to a prolonged time to
      diagnosis. Our retrospective study points out the variability of symptoms and
      suggests a diagnostic pathway to reduce the cases of undetected H&N affection in
      rheumatic disorders.

PMID- 21865283
TI  - Clopidogrel: a drug with potential to prevent steroid-induced osteonecrosis?

PMID- 21865284
TI  - ERAP1 polymorphisms and haplotypes are associated with ankylosing spondylitis
      susceptibility and functional severity in a Spanish population.
AB  - OBJECTIVES: The aim of this study was to assess the involvement of the
      endoplasmic reticulum aminopeptidase 1 (ERAP1) gene in AS susceptibility and
      functional severity in a Spanish population. METHODS: Eight single nucleotide
      polymorphisms (SNPs) spanning the ERAP1 gene were genotyped by allele-specific
      fluorescent PCR in 300 AS Spanish patients and 300 spondylarthritis-free
      controls. The influence of the ERAP1 SNPs on the functional severity of AS was
      analysed with the BASFI corrected for disease duration. Association analyses with
      AS susceptibility and functional severity were performed. RESULTS: Significant
      ERAP1 single marker association with AS susceptibility was found for five SNPs,
      namely rs30187 (allele T: P = 0.035), rs17482078 (allele C: P = 0.030), rs2287987
      (allele T: P = 0.028), rs26653 (allele C: P = 0.041) and rs10050860 (allele C: P
      = 0.018). Three of the associated SNPs (rs17482078, rs2287987 and rs10050860)
      were in strong linkage disequilibrium. After imputing genotypes with the HapMap
      CEU data as reference, the strongest association was with rs41135 (P = 0.0046) in
      the 5'-upstream region of ERAP1. In addition, the SNP rs17481856 was found to be
      a risk factor for functional severity in AS and a borderline trend was observed
      for rs27044. CONCLUSIONS: These results suggest that the ERAP1 gene is associated
      with genetic predisposition to AS and influences the functional severity of the
      disease in a Spanish population.

PMID- 21865285
TI  - Incidence of osteonecrosis associated with corticosteroid therapy among different
      underlying diseases: prospective MRI study.
AB  - OBJECTIVES: The purpose of this study was to clarify the incidence of (CS)
      associated osteonecrosis among different underlying diseases and to evaluate the
      risk factors for steroid-associated osteonecrosis in a prospective MRI study.
      METHODS: We prospectively used MRI to study 337 eligible underlying disease
      patients requiring CS therapy and succeeded in examining 1199 joints (hips and
      knees) in 302 patients with MRI for at least 1 year starting immediately after
      the onset of CS therapy (1-year follow-up rate of 90%). The underlying diseases
      included SLE in 687 joints (173 patients) and a variety of other rheumatological
      disorders in 512 joints (129 patients). RESULTS: The incidence of osteonecrosis
      was significantly higher in SLE patients than in non-SLE patients (37 vs 21%, P =
      0.001). Logistic regression analysis revealed that adolescent and adult patients
      had a significantly higher risk of osteonecrosis compared with paediatric
      patients [odds ratio (OR) = 13.2], that high daily CS dosage (>40 mg/day)
      entailed a significantly higher risk of osteonecrosis compared with the dosage of
      <40 mg/day (OR = 4.2), that SLE patients had a significantly higher risk of
      osteonecrosis compared with non-SLE patients (OR = 2.6) and that male patients
      had a significantly higher risk of osteonecrosis compared with female patients
      (OR = 1.6). CONCLUSION: These findings suggest that the incidence of CS
      associated osteonecrosis varies among different underlying diseases.

PMID- 21865286
TI  - Inadvertent intraarterial injection of 18F-FDG: a case report and literature
      review of hot forearm and hot hand signs.
AB  - Unintentional intraarterial injection of radiotracers may cause artifacts leading
      to difficulties in accurately interpreting PET/CT images. We report a case of a
      73-y-old man with a history of metastatic colon cancer who underwent a PET/CT
      scan for restaging. In the PET scan, there was intense and diffuse distribution
      of (18)F-FDG in his left forearm and hand. This is a classic sign of an
      accidental intraarterial injection of (18)F-FDG in the antecubital region.
      Similar phenomena after inadvertent intraarterial injection of other radiotracers
      are reviewed. The associated risk factors, preventive measures, and radiation
      dose to the arm are discussed.

PMID- 21865287
TI  - Comprehensive approach to coregistration of autoradiography and microscopy images
      acquired from a set of sequential tissue sections.
AB  - Histopathologic validation of a PET tracer requires assessment of colocalization
      of the tracer with its intended biologic target. Using thin tissue section
      autoradiography, it is possible to visualize the spatial distribution of the PET
      tracer uptake and compare it with the distribution of the intended biologic
      target (as visualized with immunohistochemistry). The purpose of this study was
      to develop and evaluate an objective methodology for deformable coregistration of
      autoradiography and microscopy images acquired from a set of sequential tissue
      sections. METHODS: Tumor-bearing animals were injected with 3'-deoxy-3'-(18)F
      fluorothymidine ((18)F-FLT), (14)C-FDG, and other markers of tumor
      microenvironment including Hoechst 33342 (blood-flow surrogate). After sacrifice,
      tumors were excised, frozen, and sectioned. Multiple stacks of sequential 8 MUm
      sections were collected from each tumor. From each stack, the middle (reference)
      sections were used to obtain images of (18)F-FLT and (14)C-FDG uptake
      distributions using dual-tracer autoradiography. Sections adjacent to the
      reference were used to acquire all histopathologic data (e.g., images of cell
      proliferation, hematoxylin and eosin). Hoechst images were acquired from all
      sections. To correct for deformations and misalignments induced by tissue
      processing and image acquisition, the Hoechst image of each nonreference section
      was deformably registered to the reference Hoechst image. This transformation was
      then applied to all images acquired from the same tissue section. In this way,
      all microscopy images were registered to the reference Hoechst image. The Hoechst
      to-autoradiography image registration was done using rigid point-set registration
      based on external markers visible in both images. RESULTS: The mean error of
      Hoechst to (18)F-FLT autoradiography registration (both images acquired from the
      same section) was 30.8 +/- 20.1 MUm. The error of Hoechst-based deformable
      registration of histopathologic images (acquired from sequential tissue sections)
      was 23.1 +/- 17.9 MUm. Total error of registration of autoradiography images to
      the histopathologic images acquired from adjacent sections was evaluated at 44.9
      MUm. This coregistration precision supersedes current rigid registration methods
      with reported errors of 100-200 MUm. CONCLUSION: Deformable registration of
      autoradiography and histopathology images acquired from sequential sections is
      feasible and accurate when performed using corresponding Hoechst images.

PMID- 21865288
TI  - Imaging of prostate cancer with immuno-PET and immuno-SPECT using a radiolabeled
      anti-EGP-1 monoclonal antibody.
AB  - hRS7 is a humanized IgG1 monoclonal antibody directed against the epithelial
      glycoprotein-1 (EGP-1; also known as TROP2). This antigen is found in many
      epithelial cancers, including prostate cancer, and therefore this antibody could
      be suitable for targeting this cancer. In this study, the characteristics of hRS7
      for targeting prostate cancer were examined. The potential for immuno-PET with
      (89)Zr-hRS7 and immuno-SPECT with (111)In-hRS7 was assessed using nude mice with
      human prostate cancer xenografts. METHODS: EGP-1 expression was assessed by
      immunohistology in human primary and metastatic prostate cancer samples and in
      PC3 xenografts. The optimal antibody protein dose for prostate cancer targeting
      was examined in nude mice with subcutaneous PC3 xenografts, and then the
      biodistribution of (111)In-, (125)I-, and (89)Zr-labeled hRS7 was determined in
      subcutaneous PC3 xenografts at 1, 3, and 7 d after injection. Immuno-PET and
      immuno-SPECT were performed with (89)Zr-hRS7 and (111)In-hRS7 in mice with
      subcutaneous and intraprostatic PC3 xenografts, respectively. RESULTS:
      Immunohistochemical analysis showed abundant EGP-1 expression in human primary
      and metastatic prostate cancers and in PC3 xenografts. (111)In-hRS7 and (89)Zr
      hRS7 preferentially and specifically accumulated in PC3 xenografts, with tumor
      uptake as high as 60% injected dose per gram at a protein dose of 0.1 MUg per
      mouse. PC3 tumors in nude mice were clearly visualized with both tracers with
      immuno-PET and immuno-SPECT. CONCLUSION: hRS7 shows excellent in vivo tumor
      targeting in human prostate cancer xenografts. Therefore, hRS7 is a potential
      vehicle for targeting prostate cancer.

PMID- 21865289
TI  - Doxorubicin-induced platelet procoagulant activities: an important clue for
      chemotherapy-associated thrombosis.
AB  - Thrombotic risk associated with chemotherapy including doxorubicin (DOX) has been
      frequently reported; yet, the exact mechanism is not fully understood. Here, we
      report that DOX can induce procoagulant activity in platelets, an important
      contributor to thrombus formation. In human platelets, DOX increased
      phosphatidylserine (PS) exposure and PS-bearing microparticle (MP) generation.
      Consistently, DOX-treated platelets and generated MPs induced thrombin
      generation, a representative marker for procoagulant activity. DOX-induced PS
      exposure appeared to be from intracellular Ca2+ increase and ATP depletion, which
      resulted in the activation of scramblase and inhibition of flippase. Along with
      this, apoptosis was induced by DOX as determined by the dissipation of
      mitochondrial membrane potential (Deltapsi), cytochrome c release, Bax
      translocation, and caspase-3 activation. A Ca2+ chelator ethylene glycol
      tetraacetic acid, caspase inhibitor Q-VD-OPh, and antioxidants (vitamin C and
      trolox) can attenuate DOX-induced PS exposure and procoagulant activity
      significantly, suggesting that Ca2+, apoptosis, and reactive oxygen species (ROS)
      were involved in DOX-enhanced procoagulant activity. Importantly, rat in vivo
      thrombosis model demonstrated that DOX could manifest prothrombotic effects
      through the mediation of platelet procoagulant activity, which was accompanied by
      increased PS exposure and Deltapsi dissipation in platelets.

PMID- 21865290
TI  - ATP mediates neuroprotective and neuroproliferative effects in mouse olfactory
      epithelium following exposure to satratoxin G in vitro and in vivo.
AB  - Intranasal aspiration of satratoxin G (SG), a mycotoxin produced by the black
      mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory
      neurons (OSNs) in mouse olfactory epithelium (OE) through unknown mechanisms.
      Here, we show a dose-dependent induction of apoptosis 24 h post-SG exposure in
      vitro as measured by increased activated caspases in the OP6 olfactory placodal
      cell line and increased propidium iodide staining in primary OE cell cultures.
      Intranasal aspiration of SG increased TUNEL (Terminal dUTP Nick End Labeling)
      staining in the neuronal layer of the OE and significantly increased the latency
      to find a buried food pellet, confirming that SG selectively induces neuronal
      apoptosis and demonstrating that SG impairs the sense of smell. Next, we
      investigated whether ATP can prevent SG-induced OE toxicity. ATP did not decrease
      apoptosis under physiological conditions but significantly reduced SG-induced OSN
      apoptosis in vivo and in vitro. Furthermore, purinergic receptor inhibition
      significantly increased apoptosis in OE primary cell culture and in vivo. These
      data indicate that ATP is neuroprotective against SG-induced OE toxicity. The
      number of cells that incorporated 5'-bromodeoxyuridine, a measure of
      proliferation, was significantly increased 3 and 6 days post-SG aspiration.
      Treatment with purinergic receptor antagonists significantly reduced SG-induced
      cell proliferation, whereas post-treatment with ATP significantly potentiated SG
      induced cell proliferation. These data indicate that ATP is released and promotes
      cell proliferation via activation of purinergic receptors in SG-induced OE
      injury. Thus, the purinergic system is a therapeutic target to alleviate or
      restore the loss of OSNs.

PMID- 21865293
TI  - Paramedics experiences and expectations concerning advance directives: a
      prospective, questionnaire-based, bi-centre study.
AB  - BACKGROUND: Advance directives and palliative crisis cards are means by which
      palliative care patients can exert their autonomy in end-of-life decisions. AIM:
      To examine paramedics' attitudes towards advance directives and end-of-life care.
      DESIGN: Questionnaire-based investigation using a self-administered survey
      instrument. SETTING/PARTICIPANTS: Paramedics of two cities (Hamburg and
      Goettingen, Germany) were included. Participants were questioned as to (1) their
      attitudes about advance directives, (2) their clinical experiences in connection
      with end-of-life situations (e.g. resuscitation), (3) their suggestions in regard
      to advance directives, 'Do not attempt resuscitation' orders and palliative
      crisis cards. RESULTS: Questionnaires were returned by 728 paramedics (response
      rate: 81%). The majority of paramedics (71%) had dealt with advance directives
      and end-of-life decisions in emergency situations. Most participants (84%) found
      that cardiopulmonary resuscitation in end-of-life patients is not useful and 75%
      stated that they would withhold cardiopulmonary resuscitation in the case of
      legal possibility. Participants also mentioned that more extensive discussion of
      legal aspects concerning advance directives should be included in paramedic
      training curricula. They suggested that palliative crisis cards should be
      integrated into end-of-life care. CONCLUSIONS: Decision making in prehospital end
      of-life care is a challenge for all paramedics. The present investigation
      demonstrates that a dialogue bridging emergency medical and palliative care
      issues is necessary. The paramedics indicated that improved guidelines on end-of
      life decisions and the termination of cardiopulmonary resuscitation in palliative
      care patients may be essential. Participants do not feel adequately trained in
      end-of-life care and the content of advance directives. Other recent studies have
      also demonstrated that there is a need for training curricula in end-of-life care
      for paramedics.

PMID- 21865291
TI  - Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague
      Dawley rats.
AB  - Homeostasis of selenium (Se), a critical antioxidant incorporated into amino
      acids and enzymes, is disrupted by exposure to aryl hydrocarbon receptor (AhR)
      agonists. Here we examined the importance of dietary Se in preventing the
      toxicity of the most toxic polychlorinated biphenyl congener, 3,3',4,4',5
      pentachlorobiphenyl (PCB 126), a potent AhR agonist. Male Sprague-Dawley rats
      were fed a modified AIN-93 diet with differing dietary Se levels (0.02, 0.2, and
      2 ppm). Following 3 weeks of acclimatization, rats from each dietary group were
      given a single ip injection of corn oil (vehicle), 0.2, 1, or 5 MUmol/kg body
      weight PCB 126, followed 2 weeks later by euthanasia. PCB exposure caused dose
      dependent increases in liver weight and at the highest PCB 126 dose decreases in
      whole body weight gains. Hepatic cytochrome P-450 (CYP1A1) activity was
      significantly increased even at the lowest dose of PCB 126, indicating potent AhR
      activation. PCB exposure diminished hepatic Se levels in a dose-dependent manner,
      and this was accompanied by diminished Se-dependent glutathione peroxidase
      activity. Both these effects were partially mitigated by Se supplementation.
      Conversely, thioredoxin (Trx) reductase activity and Trx oxidation state,
      although significantly diminished in the lowest dietary Se groups, were not
      affected by PCB exposure. In addition, PCB 126-induced changes in hepatic copper,
      iron, manganese, and zinc were observed. These results demonstrate that
      supplemental dietary Se was not able to completely prevent the toxicity caused by
      PCB 126 but was able to increase moderately the levels of several key
      antioxidants, thereby maintaining them roughly at normal levels.

PMID- 21865292
TI  - Genomic-derived markers for early detection of calcineurin inhibitor
      immunosuppressant-mediated nephrotoxicity.
AB  - Calcineurin inhibitor (CI) therapy has been associated with chronic
      nephrotoxicity, which limits its long-term utility for suppression of allograft
      rejection. In order to understand the mechanisms of the toxicity, we analyzed
      gene expression changes that underlie the development of CI immunosuppressant
      mediated nephrotoxicity in male Sprague-Dawley rats dosed daily with cyclosporine
      (CsA; 2.5 or 25 mg/kg/day), FK506 (0.6 or 6 mg/kg/day), or rapamycin (1 or 10
      mg/kg/day) for 1, 7, 14, or 28 days. A significant increase in blood urea
      nitrogen was observed in animals treated with CsA (high) or FK506 (high) for 14
      and 28 days. Histopathological examination revealed tubular basophilia and
      mineralization in animals given CsA (high) or FK506 (low and high). We identified
      a group of genes whose expression in rat kidney is correlated with CI-induced
      kidney injury. Among these genes are two genes, Slc12a3 and kidney-specific Wnk1
      (KS-Wnk1), that are known to be involved in sodium transport in the distal
      nephrons and could potentially be involved in the mechanism of CI-induced
      nephrotoxicity. The downregulation of NCC (the Na-Cl cotransporter coded by
      Slc12a3) in rat kidney following CI treatment was confirmed by
      immunohistochemical staining, and the downregulation of KS-Wnk1 was confirmed by
      quantitative real-time-polymerase chain reaction (qRT-PCR). We hypothesize that
      decreased expression of Slc12a3 and KS-Wnk1 could alter the sodium chloride
      reabsorption in the distal tubules and contribute to the prolonged activation of
      the renin-angiotensin system, a demonstrated contributor to the development of CI
      induced nephrotoxicity in both animal models and clinical settings. Therefore, if
      validated as biomarkers in humans, SLC12A3 and KS-WNK1 could potentially be
      useful in the early detection and reduction of CI-related nephrotoxicity in
      immunosuppressed transplant patients when monitoring the health of kidney
      xenographs in clinical practice.

PMID- 21865294
TI  - The evaluation of complex interventions in palliative care: an exploration of the
      potential of case study research strategies.
AB  - BACKGROUND: Complex, incrementally changing, context dependent and variable
      palliative care services are difficult to evaluate. Case study research
      strategies may have potential to contribute to evaluating such complex
      interventions, and to develop this field of evaluation research. AIM: This paper
      explores definitions of case study (as a unit of study, a process, and a product)
      and examines the features of case study research strategies which are thought to
      confer benefits for the evaluation of complex interventions in palliative care
      settings. RESULTS: Ten features of case study that are thought to be beneficial
      in evaluating complex interventions in palliative care are discussed, drawing
      from exemplars of research in this field. Important features are related to a
      longitudinal approach, triangulation, purposive instance selection, comprehensive
      approach, multiple data sources, flexibility, concurrent data collection and
      analysis, search for proving-disproving evidence, pattern matching techniques and
      an engaging narrative. The limitations of case study approaches are discussed
      including the potential for subjectivity and their complex, time consuming and
      potentially expensive nature. CONCLUSIONS: Case study research strategies have
      great potential in evaluating complex interventions in palliative care settings.
      Three key features need to be exploited to develop this field: case selection,
      longitudinal designs, and the use of rival hypotheses. In particular, case study
      should be used in situations where there is interplay and interdependency between
      the intervention and its context, such that it is difficult to define or find
      relevant comparisons.

PMID- 21865296
TI  - Symptom clusters in patients with advanced cancer: sub-analysis of patients
      reporting exclusively non-zero ESAS scores.
AB  - BACKGROUND: Advanced cancer patients often experience multiple concurrent
      symptoms, which can have prognostic effects on patients' quality of life.
      Including patients who did not experience all of the symptoms measured by an
      assessment tool may interfere with accurate symptom cluster identification.
      Varying statistical methods may also contribute to inconsistencies of cluster
      results. AIMS: To compare symptom clusters in a subgroup of patients reporting
      exclusively non-zero ESAS scores with those in the total patient sample. To
      examine whether using different statistical methods results in varied symptom
      clusters. DESIGN: Principal Component Analysis (PCA), Hierarchical Cluster
      Analysis (HCA) and Exploratory Factor Analysis (EFA) were performed on the 'non
      zero' subgroup and the total patient sample to identify symptom clusters at
      baseline and weeks 1, 2, 4, 8 and 12 following palliative radiotherapy.
      SETTING/PARTICIPANTS: A previous single-centre study used Principal Component
      Analysis to explore symptom clusters in 1296 advanced cancer patients. The
      present study analyzed this previously reported data set. RESULTS: Notably
      different symptom clusters were extracted between the two patient groups
      regardless of the statistical method at baseline, with the exception of a cluster
      composed of drowsiness, fatigue and dyspnea using Principal Component Analysis
      and Hierarchical Cluster Analysis. At follow-ups, different statistical methods
      yielded significantly varied symptom clusters. Only anxiety, depression and well
      being consistently occurred in the same cluster across methods and over time.
      CONCLUSIONS: The composition of symptom clusters varied depending on if patients
      with non-zero scores were excluded at baseline and on the statistical method
      employed. Identifying valid clusters may prove useful for bettering symptom
      diagnosis and management for cancer patients.

PMID- 21865295
TI  - A systematic review on the role of fish oil for the treatment of cachexia in
      advanced cancer: an EPCRC cachexia guidelines project.
AB  - BACKGROUND: The European Palliative Care Research Collaboration is developing
      clinical guidelines on cachexia in patients with advanced cancer. A systematic
      review on the use of fish oil/omega-3-fatty acids (n-3-FA)/eicosapentaenoic acids
      (EPA) in advanced cancer patients suffering from cancer cachexia was performed as
      part of the guideline development. METHODS: The systematic literature search in
      Medline on the use of fish oil/n-3-FA/EPA identified 244 papers, with 38
      publications included in the final evaluation. Some smaller trials, often
      unrandomized and without a control group, reported a good effect of n-3-FA in
      patients with advanced cancer and cachexia. However, the results of the larger
      randomized controlled trials could not support the positive results, as they
      mostly did not find a significant effect. RESULTS: Adverse effects such as
      abdominal discomfort, fish belching, fish aftertaste, nausea and diarrhoea were
      reported with a low incidence. No serious adverse effects were documented, but
      adverse effects often had an impact on quality of life. This often limited dose
      escalations or even led to discontinuation of n-3-FA. CONCLUSION: There is not
      enough evidence to support a net benefit of n-3-FA in cachexia in advanced
      cancer. On the other hand, adverse effects were infrequent, with no severe
      adverse effects. The results from the review led to a weak negative GRADE
      recommendation.

PMID- 21865297
TI  - Action research in palliative care: defining an evaluation methodology.
AB  - BACKGROUND: Action research is beginning to be utilized within palliative care
      research to address questions concerned with practice and organizational change.
      An understanding of appropriate evaluation practices is required in order to
      ensure that high-quality action research is conducted. AIM: The aim of this paper
      is to present an account of participatory action research and illustrate the way
      in which evaluation approaches are integrated within this methodology. DESIGN:
      Participatory action research will be described identifying its origins,
      principles and its relationship with evaluation frameworks. The key features of
      the evaluation process in regard to participatory research are outlined. SETTING:
      Two studies are presented which illustrate the integration of evaluation within a
      participatory action research framework. The first approach uses a before-after
      summative evaluation approach in a study undertaken to develop palliative care
      practice within a UK nursing home context. The evaluation focused upon the impact
      of the intervention. The second study utilized similar methods and addressed the
      process of the action research using the Aldrevast Sjuharad (AVS) model to
      evaluate participation in a peer education programme for advance care planning
      amongst older adults. RESULTS: These examples of evaluation within action
      research illustrate how diverse methods can be used. The use of a specific
      participatory evaluation model ensures the process reflects the underlying
      participatory principle of action research. CONCLUSIONS: Evaluation processes are
      integral to action research approaches. The specific evaluative methods adopted
      will reflect the nature and focus of the evaluation being undertaken.

PMID- 21865298
TI  - Use of array CGH to detect exonic copy number variants throughout the genome in
      autism families detects a novel deletion in TMLHE.
AB  - Autism is a neurodevelopmental disorder with increasing evidence of heterogeneous
      genetic etiology including de novo and inherited copy number variants (CNVs). We
      performed array comparative genomic hybridization using a custom Agilent 1 M
      oligonucleotide array intended to cover 197 332 unique exons in RefSeq genes; 98%
      were covered by at least one probe and 95% were covered by three or more probes
      with the focus on detecting relatively small CNVs that would implicate a single
      protein-coding gene. The study group included 99 trios from the Simons Simplex
      Collection. The analysis identified and validated 55 potentially pathogenic CNVs,
      categorized as de novo autosomal heterozygous, inherited homozygous autosomal,
      complex autosomal and hemizygous deletions on the X chromosome of probands.
      Twenty percent (11 of 55) of these CNV calls were rare when compared with the
      Database of Genomic Variants. Thirty-six percent (20 of 55) of the CNVs were also
      detected in the same samples in an independent analysis using the 1 M Illumina
      single-nucleotide polymorphism array. Findings of note included a common and
      sometimes homozygous 61 bp exonic deletion in SLC38A10, three CNVs found in
      lymphoblast-derived DNA but not present in whole-blood derived DNA and, most
      importantly, in a male proband, an exonic deletion of the TMLHE (trimethyllysine
      hydroxylase epsilon) that encodes the first enzyme in the biosynthesis of
      carnitine. Data for CNVs present in lymphoblasts but absent in fresh blood DNA
      suggest that these represent clonal outgrowth of individual B cells with pre
      existing somatic mutations rather than artifacts arising in cell culture. GEO
      accession number GSE23765 (http://www.ncbi.nlm.nih.gov/geo/, date last accessed
      on 30 August 2011). Genboree accession: http://genboree.org/java
      bin/gbrowser.jsp?refSeqId=1868&entryPointId=chr17&from=53496072&to=53694382&isPub
      ic=yes, date last accessed on 30 August 2011.

PMID- 21865300
TI  - The selective footprints of viral pressures at the human RIG-I-like receptor
      family.
AB  - The RIG-I-like receptors (RLRs)--RIG-I, IFIH1 (or MDA5) and LGP2--are thought to
      be key actors in the innate immune system, as they play a major role in sensing
      RNA viruses in the cytosol of host cells. Despite the increasingly recognized
      importance of the RLR family in antiviral immunity, no population genetic studies
      have yet attempted to compare the evolutionary history of its different members
      in humans. Here, we characterized the levels of naturally occurring genetic
      variation in the RLRs in a panel of individuals of different ethnic origins, to
      assess to what extent natural selection has acted on this family of microbial
      sensors. Our results show that amino acid-altering variation at RIG-I,
      particularly in the helicase domain, has been under stronger evolutionary
      constraint than that at IFIH1 and LGP2, reflecting an important role for RIG-I in
      sensing numerous RNA viruses and/or functional constraints related to the binding
      of viral substrates. Such evolutionary constraints have been much more relaxed at
      IFIH1 and LGP2, which appear to have evolved adaptively in specific human
      populations. Notably, we identified several mutations showing signatures of
      positive selection, including two non-synonymous polymorphisms in IFIH1 (R460H
      and R843H) and one in LGP2 (Q425R), suggesting a selective advantage related to
      the sensing of RNA viruses by IFIH and to the regulatory functions of LGP2. In
      light of the fact that some of these mutations have been associated with altered
      risks of developing autoimmune disorders, our study provides an additional
      example of the evolutionary conflict between infection and autoimmunity.

PMID- 21865299
TI  - Functional and physical interaction between the mismatch repair and FA-BRCA
      pathways.
AB  - Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow
      failure and an increased risk for leukemia and cancer. Fifteen proteins thought
      to function in the repair of DNA interstrand crosslinks (ICLs) comprise what is
      known as the FA-BRCA pathway. Activation of this pathway leads to the
      monoubiquitylation and chromatin localization of FANCD2 and FANCI. It has
      previously been shown that FANCJ interacts with the mismatch repair (MMR) complex
      MutLalpha. Here we show that FANCD2 interacts with the MMR proteins MSH2 and
      MLH1. FANCD2 monoubiquitylation, foci formation and chromatin loading are greatly
      diminished in MSH2-deficient cells. Human or mouse cells lacking MSH2 or MLH1
      display increased sensitivity and radial formation in response to treatment with
      DNA crosslinking agents. Studies in human cell lines and Drosophila mutants
      suggest an epistatic relationship between FANCD2, MSH2 and MLH1 with regard to
      ICL repair. Surprisingly, the interaction between MSH2 and MLH1 is compromised in
      multiple FA cell lines, and FA cell lines exhibit deficient MMR. These results
      suggest a significant role for MMR proteins in the activation of the FA pathway
      and repair of ICLs. In addition, we provide the first evidence for a defect in
      MMR in FA cell lines.

PMID- 21865301
TI  - SDRS--an algorithm for analyzing large-scale dose-response data.
AB  - SUMMARY: Dose-response information is critical to understanding drug effects, yet
      analytical methods for dose-response assays cannot cope with the dimensionality
      of large-scale screening data such as the microarray profiling data. To overcome
      this limitation, we developed and implemented the Sigmoidal Dose Response Search
      (SDRS) algorithm, a grid search-based method designed to handle large-scale dose
      response data. This method not only calculates the pharmacological parameters for
      every assay, but also provides built-in statistic that enables downstream
      systematic analyses, such as characterizing dose response at the transcriptome
      level. AVAILABILITY: Bio::SDRS is freely available from CPAN (www.cpan.org).
      CONTACTS: ruiruji@gmail.com; bruc@acm.org SUPPLEMENTARY INFORMATION:
      Supplementary data is available at Bioinformatics online.

PMID- 21865302
TI  - Thermostability of two cyanobacterial GrpE thermosensors.
AB  - GrpE proteins act as co-chaperones for DnaK heat-shock proteins. The dimeric
      protein unfolds under heat stress conditions, which results in impaired
      interaction with a DnaK protein. Since interaction of GrpE with DnaK is crucial
      for the DnaK chaperone activity, GrpE proteins act as a thermosensor in bacteria.
      Here we have analyzed the thermostability and function of two GrpE homologs of
      the mesophilic cyanobacterium Synechocystis sp. PCC 6803 and of the thermophilic
      cyanobacterium Thermosynechococcus elongatus BP1. While in Synechocystis an N
      terminal helix pair of the GrpE dimer appears to be the thermosensing domain and
      mainly mediates GrpE dimerization, the C-terminal four-helix bundle is involved
      in additional stabilization of the dimeric structure. The four-helix bundle
      domain has a key role in the thermophilic cyanobacterium, since dimerization of
      the Thermosynechococcus protein appears to be mediated by the four-helix bundle
      domain, and melting of this domain is linked to monomerization of the GrpE
      protein. Thus, in two related cyanobacteria the GrpE thermosensing function might
      be mediated by different protein domains.

PMID- 21865304
TI  - The trade-off between safety and efficiency in hydraulic architecture in 31 woody
      species in a karst area.
AB  - Karst topography is a special landscape shaped by the dissolution of one or more
      layers of soluble bedrock, usually carbonate rock such as limestone or dolomite.
      Due to subterranean drainage, overland flow, extraction of water by plants and
      evapotranspiration, there may be very limited surface water. The hydraulic
      architecture that plants use to adapt to karst topography is very interesting,
      but few systematic reports exist. The karst area in southwestern China is unique
      when compared with other karst areas at similar latitudes, because of its
      abundant precipitation, with rainfall concentrated in the growing season. In
      theory, resistance to water-stress-induced cavitation via air seeding should be
      accompanied by decreased pore hydraulic conductivity and stem hydraulic
      conductivity. However, evidence for such trade-offs across species is ambiguous.
      We measured the hydraulic structure and foliar stable carbon isotope ratios of 31
      karst woody plants at three locations in Guizhou Province, China, to evaluate the
      functional coordination between resistance to cavitation and specific
      conductivity. We also applied phylogenetically independent contrast (PIC)
      analysis in situations where the inter-species correlations of functional traits
      may be biased on the potential similarity of closely related species. The average
      xylem tension measurement, at which 50% of hydraulic conductivity of the plants
      was lost (Psi(50)), was only -1.27 MPa. Stem Psi(50) was positively associated
      with specific conductance (K(s)) (P < 0.05) and leaf specific conductance (K(l))
      (P < 0.05). However, the PIC correlation for both relationships was not
      statistically significant. delta(13)C was positively related to K(l) in both the
      traditional cross-species correlation analysis and the corresponding PIC
      correlations (P < 0.05). The Huber value (sapwood area:leaf area ratio) was
      negatively correlated with K(s) in both the traditional cross-species correlation
      and the corresponding PIC correlations (P < 0.01). The characteristics of
      hydraulic architecture measured in this study showed that karst plants in China
      are not highly cavitation-resistant species. This study also supports the idea
      that there may not be an evolutionary trade-off between resistance to cavitation
      and specific conductivity in woody plants. Whole-plant hydraulic adjustment may
      decouple the trade-off relationship between safety and efficiency at the branch
      level.

PMID- 21865303
TI  - ABA-mediated heterophylly is regulated by differential expression of 9-cis
      epoxycarotenoid dioxygenase 3 in lilies.
AB  - Although exogenous ABA-regulated heterophylly has been well documented in
      multiple plant species, the effect of endogenous ABA and its molecular mechanism
      remain uncharacterized. In the present study, the effects of endogenous ABA on
      heterophyllous switching were investigated in two different lily varieties,
      Lilium formosanum and Lilium oriental hybrid 'Casa Blanca'. Seedlings of L.
      formosanum, which have scale-leaf-type growth, displayed low levels of both 9-cis
      epoxycarotenoid dioxygenase 3 (LfNCED3) transcripts and ABA, whereas seedlings of
      L. oriental hybrid 'Casa Blanca', which have scale-type growth, displayed high
      levels of both LoNCED3 transcripts and ABA. Sucrose induced endogenous ABA
      production in cultured lilies; low ABA induction shows scale-leaf-type growth,
      whereas scale-type growth becomes predominant when ABA levels are high.
      Heterologous expression of either LfNCED3 or LoNCED3 was found to complement the
      Arabidopsis Atnced3 mutant. Interestingly, the expression patterns of LfNCED3 and
      LoNCED3 in transgenic Arabidopsis plants are distinguishable. Further promoter
      analysis revealed that a putative E2F-like element in the LfNCED3 promoter, but
      not in the LoNCED3 promoter, plays a negative role in controlling its activity.
      Collectively, our results demonstrate that NCED3 plays a key role in ABA-mediated
      heterophylly in lilies.

PMID- 21865305
TI  - Flagellate erythema secondary to bleomycin.

PMID- 21865306
TI  - 'Hair-on-end' sign: an important finding in clinical practice.

PMID- 21865307
TI  - A difficult diagnosis.

PMID- 21865308
TI  - Quality of resuscitation orders in general medical patients.
AB  - BACKGROUND: Documentation of resuscitation status in hospitalized patients has
      relevance in the management of cardiopulmonary arrest. Its association with
      mortality, Length Of hospital Stay (LOS) and the patients' primary diagnosis has
      not been established in general medical inpatients in hospitals in Australia and
      New Zealand. AIM: To investigate the association of resuscitation orders with in
      hospital mortality and LOS in a range of diagnoses, adjusting for severity of
      illness and other covariates. DESIGN: Retrospective study. METHODS: The admission
      notes of 1681 medical admissions to four tertiary care teaching hospitals across
      Australia and New Zealand were reviewed retrospectively for frequency and nature
      of resuscitation documentation and its association with mortality, LOS and
      primary diagnosis. RESULTS: Resuscitation orders were documented in 741 patients
      (44.7%). For the 232 patients with a Not For Resuscitation (NFR) order, the in
      hospital mortality rate was higher than in control patients (14% vs. 1.2%,
      P<0.005). The mortality rate remained significantly higher in the NFR group after
      propensity matching of the controls for age and co-morbidity (14% vs. 5%,
      P<0.005). The death-adjusted LOS for the NFR group was also significantly higher
      compared to the control patients (9.7 days vs. 4.7 days, P<0.005) and this
      difference remained after propensity matching (9.7 days vs. 7.7 days, P<0.05).
      Those patients with a primary diagnosis of respiratory tract infection or cardiac
      failure were more likely to be documented NFR compared to those with cellulitis
      or urinary tract infection. CONCLUSIONS: The documentation of NFR in a patient's
      admission notes is associated with increased in-hospital mortality and LOS. This
      is only partly explicable in terms of these patients' greater age and co
      morbidity.

PMID- 21865309
TI  - Recurrent appendicitis after appendectomy.

PMID- 21865310
TI  - When I use a word ... Misunderspellings.

PMID- 21865311
TI  - Barium aspiration.

PMID- 21865312
TI  - Obscure gastrointestinal bleeding revealed by abdominal ultrasound.

PMID- 21865313
TI  - AAA syndrome--adrenal insufficiency, alacrima and achalasia.

PMID- 21865314
TI  - Clinical features and outcomes of posterior reversible encephalopathy syndrome
      following bevacizumab treatment.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a potentially
      devastating complication of bevacizumab treatment. AIM: We examined the clinical
      features, treatment and outcomes of patients who developed PRES following
      bevacizumab treatment at our institution and those reported in the literature.
      DESIGN: Retrospective audit and systematic review. METHODS: Patients were
      identified from the Mayo Clinic database and the published literature using
      'PubMed' and 'OVID' databases, from January 2006 to June 2010, who developed PRES
      features within 3 weeks of bevacizumab treatment, who had brain imaging findings
      of focal vasogenic edema and radiologic proof of reversibility. RESULTS: Two
      patients with definite PRES were identified from our institution and a further 10
      cases were identified from the published literature (total, n=12). The mean age
      of these patients was 52 years (range 4-68 years), four of whom were men and
      eight women. Headaches (n=7), seizures (n=6), visual disturbances (n=5) and
      nausea and vomiting (n=3) were the common presenting symptoms. In a majority of
      patients (n=10), an increase in blood pressure from their baseline values was
      observed during their acute presentation. PRES resolved following withdrawal of
      bevacizumab and blood pressure control in all patients. CONCLUSIONS: PRES is a
      catastrophic neurological complication of bevacizumab treatment, which responds
      favorably to prompt bevacizumab withdrawal and blood pressure control.

PMID- 21865315
TI  - Predicting in vivo cardiovascular properties of beta-blockers from cellular
      assays: a quantitative comparison of cellular and cardiovascular pharmacological
      responses.
AB  - beta-Adrenoceptor antagonists differ in their degree of partial agonism. In vitro
      assays have provided information on ligand affinity, selectivity, and intrinsic
      efficacy. However, the extent to which these properties are manifest in vivo is
      less clear. Conscious freely moving rats, instrumented for measurement of heart
      rate (beta1; HR) and hindquarters vascular conductance (beta2; HVC) were used to
      measure receptor selectivity and ligand efficacy in vivo. CGP 20712A caused a
      dose-dependent decrease in basal HR (P<0.05, ANOVA) at 5 doses between 6.7 and
      670 MUg/kg (i.v.) and shifted the dose-response curve for isoprenaline to higher
      agonist concentrations without altering HVC responses. In contrast, at doses of
      67 MUg/kg (i.v.) and above, ICI 118551 substantially reduced the HVC response to
      isoprenaline without affecting HR responses. ZD 7114, xamoterol, and bucindolol
      significantly increased basal HR (DeltaHR: +122 +/- 12, + 129 +/- 11, and + 59 +/
      11 beats/min, respectively; n=6), whereas other beta-blockers caused significant
      reductions (all at 2 mg/kg i.v.). The agonist effects of xamoterol and ZD 7114
      were equivalent to that of the highest dose of isoprenaline. Bucindolol, however,
      significantly antagonized the response to the highest doses isoprenaline. An
      excellent correlation was obtained between in vivo and in vitro measures of beta1
      adrenoceptor efficacy (R(2)=0.93; P<0.0001).

PMID- 21865316
TI  - A critical role for macrophages in neovessel formation and the development of
      stenosis in tissue-engineered vascular grafts.
AB  - The primary graft-related complication during the first clinical trial evaluating
      the use of tissue-engineered vascular grafts (TEVGs) was stenosis. We
      investigated the role of macrophages in the formation of TEVG stenosis in a
      murine model. We analyzed the natural history of TEVG macrophage infiltration at
      critical time points and evaluated the role of cell seeding on neovessel
      formation. To assess the function of infiltrating macrophages, we implanted TEVGs
      into mice that had been macrophage depleted using clodronate liposomes. To
      confirm this, we used a CD11b-diphtheria toxin-receptor (DTR) transgenic mouse
      model. Monocytes infiltrated the scaffold within the first few days and initially
      transformed into M1 macrophages. As the scaffold degraded, the macrophage
      infiltrate disappeared. Cell seeding decreased the incidence of stenosis (32%
      seeded, 64% unseeded, P=0.024) and the degree of macrophage infiltration at 2 wk.
      Unseeded TEVGs demonstrated conversion from M1 to M2 phenotype, whereas seeded
      grafts did not. Clodronate and DTR inhibited macrophage infiltration and
      decreased stenosis but blocked formation of vascular neotissue, evidenced by the
      absence of endothelial and smooth muscle cells and collagen. These findings
      suggest that macrophage infiltration is critical for neovessel formation and
      provides a strategy for predicting, detecting, and inhibiting stenosis in TEVGs.

PMID- 21865317
TI  - Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially
      a useful biomarker for Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by the presence of Lewy bodies
      containing phosphorylated and aggregated alpha-synuclein (alpha-syn). alpha-Syn
      is present in human body fluids, including blood plasma, and is a potential
      biomarker for PD. Immunoassays for total and oligomeric forms of both normal and
      phosphorylated (at Ser-129) alpha-syn have been used to assay plasma samples from
      a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well
      as single plasma samples from a group of 30 healthy control participants. The
      levels of alpha-syn in plasma varied greatly between individuals, but were
      remarkably consistent over time within the same individual with PD. The mean
      level of phospho-alpha-syn was found to be higher (P=0.053) in the PD samples
      than the controls, whereas this was not the case for total alpha-syn (P=0.244),
      oligo-alpha-syn (P=0.221), or oligo-phospho-alpha-syn (P=0.181). Immunoblots of
      plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated
      alpha-syn. Thus, phosphorylated alpha-syn can be detected in blood plasma and
      shows more promise as a diagnostic marker than the nonphosphorylated protein.
      Longitudinal studies undertaken over a more extended time period will be required
      to determine whether alpha-syn can act as a marker of disease progression.

PMID- 21865318
TI  - Defective macrophage function in aquaporin-3 deficiency.
AB  - Macrophages play an essential role in innate immunity. We found that mouse
      resident peritoneal macrophages (mRPMs) express the aquaglyceroporin aquaporin-3
      (AQP3) in a plasma membrane pattern. AQP3-deficient (AQP3(-/-)) mice showed
      significantly greater mortality than wild-type (AQP3(+/+)) mice in a model of
      bacterial peritonitis. To establish the cellular mechanism of the peritonitis
      phenotype, measurements were made of mRPM phagocytosis, migration, and
      water/glycerol permeability. We found significantly impaired engulfment of
      Escherichia coli and chicken erythrocytes in AQP3(-/-) vs. AQP3(+/+) mRPMs, as
      well as impaired migration of AQP3(-/-) mRPMs in response to a chemotactic
      stimulus. In AQP3(+/+) mRPMs, AQP3 was polarized to pseudopodia at the leading
      edge during migration and around the phagocytic cup during engulfment. Water and
      glycerol permeabilities in mRPMs from AQP3(-/-) mice were reduced compared to
      mRPMs from AQP3(+/+) mice. Cellular glycerol and ATP content were remarkably
      lower in AQP3(-/-) vs. AQP3(+/+) mRPMs, and glycerol supplementation partially
      rescued the reduced ATP content and impaired function of AQP3(-/-) mRPMs. These
      data implicate AQP3 as a novel determinant in macrophage immune function by a
      cellular mechanism involving facilitated water and glycerol transport, and
      consequent phagocytic and migration activity. This is the first study
      demonstrating involvement of an aquaporin in innate immunity. Our results suggest
      AQP3 as a novel therapeutic target in modulating the immune response in various
      infectious and inflammatory conditions.

PMID- 21865319
TI  - Differences in the disposition of silymarin between patients with nonalcoholic
      fatty liver disease and chronic hepatitis C.
AB  - Silymarin, derived from the milk thistle plant Silybum marianum and widely used
      for self-treatment of liver diseases, is composed of six major flavonolignans
      including silybin A and silybin B, which are the predominant flavonolignans
      quantified in human plasma. The single- and multiple-dose pharmacokinetics of
      silymarin flavonolignans were examined in patients with nonalcoholic fatty liver
      disease (NAFLD) or hepatitis C virus (HCV) to determine whether the disposition
      of silymarin and therefore its potential efficacy vary among liver disease
      populations. Cohorts of eight subjects with noncirrhotic liver disease were
      randomized 3:1 to oral silymarin or placebo (280 or 560 mg) every 8 h for 7 days.
      Forty-eight-hour blood sampling was conducted after the first and final doses. In
      general, plasma concentrations of silybin A and silybin B were higher, whereas
      concentrations of conjugates were lower in NAFLD compared with HCV. After
      adjustment of the area under plasma concentration-time curve from 0 to 8 h (AUC(0
      8 h)) for weight and dose, only silybin B and silybin B conjugates differed
      significantly between disease types. For NAFLD, the adjusted mean AUC(0-8 h) was
      higher for silybin B (p < 0.05) but lower for silybin B conjugates (p < 0.05)
      compared with that for HCV. At the 280-mg dose, steady-state plasma
      concentrations of silybin B conjugates for NAFLD subjects were characterized by
      46% lower AUC(0-8 h) (p < 0.05) and 42% lower C(max) (p < 0.05) compared with HCV
      subjects. Evidence of enterohepatic cycling of flavonolignans was only observed
      in NAFLD subjects. In summary, the efficacy of silymarin may be more readily
      observed in NAFLD patients because of their higher flavonolignan plasma
      concentrations and more extensive enterohepatic cycling compared with those in
      HCV patients.

PMID- 21865320
TI  - Effect of culture time on the basal expression levels of drug transporters in
      sandwich-cultured primary rat hepatocytes.
AB  - Sandwich-cultured rat hepatocytes are used in drug discovery for pharmacological
      and toxicological assessment of drug candidates, yet their utility as a
      functional model for drug transporters has not been fully characterized. To
      evaluate the system as an in vitro model for drug transport, expression changes
      of hepatic transporters relative to whole liver and freshly isolated hepatocytes
      (day 0) were examined by real-time quantitative reverse transcription-polymerase
      chain reaction for 4 consecutive days of culture. No significant differences in
      transporter expression levels were observed between freshly isolated hepatocytes
      and whole liver. Two distinct mRNA profiles were detected over time showing 1) a
      more than 5-fold decline in levels of uptake transporters such as Na(+)
      taurocholate cotransporting polypeptide (Ntcp), organic anion transporter (Oat)
      2, organic anion-transporting polypeptide (Oatp) 1a1, Oatp1a4, and Oatp1b2 and 2)
      a greater than 5-fold increase of efflux transporters P-glycoprotein (P-gp),
      breast cancer resistance protein (Bcrp), and multidrug resistance-related
      proteins (Mrp) 1, 2, 3, and 4. In addition, protein levels and functional
      activities for selected transporters were also determined. Protein levels for
      Mrp2, Bcrp, P-gp, Ntcp, and Oatp1a4 corresponded to changes in mRNA. Functional
      activities of Oatps and Oct1 exhibited a 3- and 4-fold decrease on day 2 and day
      4, respectively, relative to that on day 0, whereas a more than 10-fold reduction
      in Oat2 activity was observed. These results indicate that the cell culture
      conditions used herein did not provide an optimal environment for expression of
      all hepatic transporters. Significant time-dependent alterations in basal gene
      expression patterns of transporters were detected compared with those in liver or
      freshly isolated hepatocytes. Further work and new strategies are required to
      improve the validity of this model as an in vitro tool for in vivo drug transport
      or biliary clearance prediction.

PMID- 21865321
TI  - Pallial origin of basal forebrain cholinergic neurons in the nucleus basalis of
      Meynert and horizontal limb of the diagonal band nucleus.
AB  - The majority of the cortical cholinergic innervation implicated in attention and
      memory originates in the nucleus basalis of Meynert and in the horizontal limb of
      the diagonal band nucleus of the basal prosencephalon. Functional alterations in
      this system give rise to neuropsychiatric disorders as well as to the cognitive
      alterations described in Parkinson and Alzheimer's diseases. Despite the
      functional importance of these basal forebrain cholinergic neurons very little is
      known about their origin and development. Previous studies suggest that they
      originate in the medial ganglionic eminence of the telencephalic subpallium;
      however, our results identified Tbr1-expressing, reelin-positive neurons
      migrating from the ventral pallium to the subpallium that differentiate into
      cholinergic neurons in the basal forebrain nuclei projecting to the cortex.
      Experiments with Tbr1 knockout mice, which lack ventropallial structures,
      confirmed the pallial origin of cholinergic neurons in Meynert and horizontal
      diagonal band nuclei. Also, we demonstrate that Fgf8 signaling in the
      telencephalic midline attracts these neurons from the pallium to follow a
      tangential migratory route towards the basal forebrain.

PMID- 21865323
TI  - Rapid BAC selection for tol2-mediated transgenesis in zebrafish.
AB  - The generation of zebrafish transgenic lines that express specific fluorophores
      in a cell- or tissue-specific manner is an important technique that takes full
      advantage of the optical clarity of the embryo. Identifying promoter fragments
      that faithfully recapitulate endogenous expression patterns and levels is often
      difficult and using large genomic DNA fragments, such as bacterial artificial
      chromosomes (BACs), makes the process of transgenesis less reliable. Here we
      provide a detailed protocol that allows for BAC selection and subsequent rapid
      modification through recombineering in Escherichia coli, resulting in BACs that
      can be injected into zebrafish embryos and, aided by tol2-mediated transgenesis,
      reliably yield stable transgenic lines. A number of BACs can be prepared in
      parallel, and injection of the BACs containing CFP/YFP/RFP or Gal4 cassettes
      allows for immediate testing of whether a particular BAC will yield the desired
      result. Furthermore, since injected embryos often show widespread expression,
      recombineered BACs provide an alternative to two-color in situ hybridizations:
      BACs injected into embryos of a different transgenic reporter line thus enable in
      vivo colocalization studies. Using this protocol, we have generated 66 stable
      lines for 23 different genes, with an average transgenesis rate above 10%.
      Importantly, we provide evidence that BAC size shows no apparent correlation to
      the transgenesis rate achieved and that there are no severe position effects.

PMID- 21865322
TI  - Combinatorial activation and concentration-dependent repression of the Drosophila
      even skipped stripe 3+7 enhancer.
AB  - Despite years of study, the precise mechanisms that control position-specific
      gene expression during development are not understood. Here, we analyze an
      enhancer element from the even skipped (eve) gene, which activates and positions
      two stripes of expression (stripes 3 and 7) in blastoderm stage Drosophila
      embryos. Previous genetic studies showed that the JAK-STAT pathway is required
      for full activation of the enhancer, whereas the gap genes hunchback (hb) and
      knirps (kni) are required for placement of the boundaries of both stripes. We
      show that the maternal zinc-finger protein Zelda (Zld) is absolutely required for
      activation, and present evidence that Zld binds to multiple non-canonical sites.
      We also use a combination of in vitro binding experiments and bioinformatics
      analysis to redefine the Kni-binding motif, and mutational analysis and in vivo
      tests to show that Kni and Hb are dedicated repressors that function by direct
      DNA binding. These experiments significantly extend our understanding of how the
      eve enhancer integrates positive and negative transcriptional activities to
      generate sharp boundaries in the early embryo.

PMID- 21865324
TI  - Cell class-specific regulation of neocortical dendrite and spine growth by AMPA
      receptor splice and editing variants.
AB  - Glutamatergic transmission converging on calcium signaling plays a key role in
      dendritic differentiation. In early development, AMPA receptor (AMPAR)
      transcripts are extensively spliced and edited to generate subunits that differ
      in their biophysical properties. Whether these subunits have specific roles in
      the context of structural differentiation is unclear. We have investigated the
      role of nine GluA variants and revealed a correlation between the expression of
      flip variants and the period of major dendritic growth. In interneurons, only
      GluA1(Q)-flip increased dendritic length and branching. In pyramidal cells,
      GluA2(Q)-flop, GluA2(Q)-flip, GluA3(Q)-flip and calcium-impermeable GluA2(R)-flip
      promoted dendritic growth, suggesting that flip variants with slower
      desensitization kinetics are more important than receptors with elevated calcium
      permeability. Imaging revealed significantly higher calcium signals in pyramidal
      cells transfected with GluA2(R)-flip as compared with GluA2(R)-flop, suggesting a
      contribution of voltage-activated calcium channels. Indeed, dendritic growth
      induced by GluA2(R)-flip in pyramidal cells was prevented by blocking NMDA
      receptors (NMDARs) or voltage-gated calcium channels (VGCCs), suggesting that
      they act downstream of AMPARs. Intriguingly, the action of GluA1(Q)-flip in
      interneurons was also dependent on NMDARs and VGCCs. Cell class-specific effects
      were not observed for spine formation, as GluA2(Q)-flip and GluA2(Q)-flop
      increased spine density in pyramidal cells as well as in interneurons. The
      results suggest that AMPAR variants expressed early in development are important
      determinants for activity-dependent dendritic growth in a cell type-specific and
      cell compartment-specific manner.

PMID- 21865326
TI  - Dietary alpha-linolenic acid, linoleic acid, and n-3 long-chain PUFA and risk of
      ischemic heart disease.
AB  - BACKGROUND: n-3 (omega-3) PUFA has been proposed as having health-promoting
      effects, primarily in relation to ischemic heart disease (IHD). Whether these
      benefits can be achieved by both alpha-linolenic acid (ALA, 18:3n-3) and n-3 long
      chain PUFA (LC-PUFA) is debatable. OBJECTIVE: The objective was to examine the
      association between ALA intake and risk of IHD in healthy subjects and to see if
      this was modified by intake of n-3 LC-PUFA or linoleic acid (LA, 18:2 n-6).
      DESIGN: This was a prospective cohort study of 3277 healthy Danish women and men
      free of known IHD. RESULTS: Four hundred seventy-one cases of IHD were observed
      during a median follow-up period of 23.3 y. Higher intake of ALA was not
      significantly associated with decreased risk of IHD among women or men. Although
      the HR of IHD was stepwise decreased with increasing ALA intake in men [0.84 (95%
      CI: 0.62, 1.14) in the medium compared with the lowest tertile (reference) and
      0.83 (95% CI: 0.56, 1.24) in the highest compared with the lowest tertile], this
      change was far from significant (P-trend: 0.39). No evidence of effect
      modification by n-3 LC-PUFA or LA was observed. High n-3 LC-PUFA intake, in
      comparison with low intake, was inversely associated with risk of IHD; this trend
      was significant in women (P = 0.04; HR: 0.62; 95% CI: 0.40, 0.97) but not in men
      (P = 0.15; HR: 0.74; 95% CI: 0.51, 1.06). No associations were observed between
      intake of LA and risk of IHD. CONCLUSION: This study suggests that there is no
      association between ALA intake and risk of IHD, but a high intake of n-3 LC-PUFA
      had a significant cardioprotective effect in women.

PMID- 21865325
TI  - A role for heterochromatin protein 1gamma at human telomeres.
AB  - Human telomere function is mediated by shelterin, a six-subunit complex that is
      required for telomere replication, protection, and cohesion. TIN2, the central
      component of shelterin, has binding sites to three subunits: TRF1, TRF2, and
      TPP1. Here we identify a fourth partner, heterochromatin protein 1gamma
      (HP1gamma), that binds to a conserved canonical HP1-binding motif, PXVXL, in the
      C-terminal domain of TIN2. We show that HP1gamma localizes to telomeres in S
      phase, where it is required to establish/maintain cohesion. We further
      demonstrate that the HP1-binding site in TIN2 is required for sister telomere
      cohesion and can impact telomere length maintenance by telomerase. Remarkably,
      the PTVML HP1-binding site is embedded in the recently identified cluster of
      mutations in TIN2 that gives rise to dyskeratosis congenita (DC), an inherited
      bone marrow failure syndrome caused by defects in telomere maintenance. We show
      that DC-associated mutations in TIN2 abrogate binding to HP1gamma and that DC
      patient cells are defective in sister telomere cohesion. Our data indicate a
      novel requirement for HP1gamma in the establishment/maintenance of cohesion at
      human telomeres and, furthermore, may provide insight into the mechanism of
      pathogenesis in TIN2-mediated DC.

PMID- 21865327
TI  - Vitamin D intake from foods and supplements and depressive symptoms in a diverse
      population of older women.
AB  - BACKGROUND: Vitamin D may plausibly reduce the occurrence of depression in
      postmenopausal women; however, epidemiologic evidence is limited, and few
      prospective studies have been conducted. OBJECTIVE: We conducted a cross
      sectional and prospective analysis of vitamin D intake from foods and supplements
      and risk of depressive symptoms. DESIGN: Study participants were 81,189 members
      of the Women's Health Initiative (WHI) Observational Study who were aged 50-79 y
      at baseline. Vitamin D intake at baseline was measured by food-frequency and
      supplement-use questionnaires. Depressive symptoms at baseline and after 3 y were
      assessed by using the Burnam scale and current antidepressant medication use.
      RESULTS: After age, physical activity, and other factors were controlled for,
      women who reported a total intake of >=800 IU vitamin D/d had a prevalence OR for
      depressive symptoms of 0.79 (95% CI: 0.71, 0.89; P-trend < 0.001) compared with
      women who reported a total intake of <100 IU vitamin D/d. In analyses limited to
      women without evidence of depression at baseline, an intake of >=400 compared
      with <100 IU vitamin D/d from food sources was associated with 20% lower risk of
      depressive symptoms at year 3 (OR: 0.80; 95% CI: 0.67, 0.95; P-trend = 0.001).
      The results for supplemental vitamin D were less consistent, as were the results
      from secondary analyses that included as cases women who were currently using
      antidepressant medications. CONCLUSIONS: Overall, our findings support a
      potential inverse association of vitamin D, primarily from food sources, and
      depressive symptoms in postmenopausal women. Additional prospective studies and
      randomized trials are essential in establishing whether the improvement of
      vitamin D status holds promise for the prevention of depression, the treatment of
      depression, or both.

PMID- 21865328
TI  - Centrally located body fat is associated with lower bone mineral density in older
      Puerto Rican adults.
AB  - BACKGROUND: Fat mass is thought to be protective against osteoporosis, primarily
      because of its weight-bearing effect. Few studies have evaluated the association
      between abdominal fat mass (AFM) and bone health beyond its weight-bearing
      effect. OBJECTIVE: We tested the hypothesis that higher body weight-adjusted AFM
      is associated with poor bone health. DESIGN: A cross-sectional study was
      conducted in 629 Puerto Rican adults aged 47-79 y. Bone mineral density (BMD) of
      the femoral neck, trochanter, total femur, and lumbar spine (L2-L4) were measured
      by using dual-energy X-ray absorptiometry (DXA). AFM and total fat mass (TFM)
      were assessed by using body-composition software from whole-body DXA scans.
      Osteoporosis and osteopenia were defined as T-scores <= -2.5 and -1.0 to -2.5 SD,
      respectively, at the respective bone site. RESULTS: After confounders were
      controlled for, body weight-adjusted AFM was inversely associated with BMD at all
      4 bone sites in women and at the femoral neck in men. For TFM, small inverse
      associations were seen at the trochanter and total femur in women. In men,
      similar associations were seen at the 3 femur sites. In both sexes, the odds for
      osteoporosis or osteopenia at each of the femoral sites increased by 10-16% for
      every 100-g increase in body weight-adjusted AFM. CONCLUSIONS: Higher AFM was
      associated with poor bone health in this Puerto Rican sample. Efforts to reduce
      abdominal obesity will not only reduce the risk of chronic disease but may also
      improve bone health. This trial is registered at clinicaltrials.gov as
      NCT01231958.

PMID- 21865330
TI  - Use of mass spectrometry fingerprinting to identify urinary metabolites after
      consumption of specific foods.
AB  - BACKGROUND: The lack of robust biological markers of dietary exposure hinders the
      quantitative understanding of causal relations between diet and health.
      OBJECTIVE: We aimed to develop an efficient procedure to discover metabolites in
      urine that may have future potential as biomarkers of acute exposure to foods of
      high public health importance. DESIGN: Twenty-four participants were provided
      with a test breakfast in which the cereal component of a standardized breakfast
      was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5
      h postprandial urine samples were collected. Flow infusion electrospray
      ionization mass spectrometry followed by supervised multivariate data analysis
      was used to discover signals resulting from consumption of each test food.
      RESULTS: Fasted-state urine samples provided a universal comparator for food
      biomarker lead discovery in postprandial urine. The filtering of data features
      associated with consumption of the common components of the standardized
      breakfast improved discrimination models and readily identified metabolites that
      showed consumption of specific test foods. A combination of trimethylamine-N
      oxide and 1-methylhistidine was associated with salmon consumption. Novel
      ascorbate derivatives were discovered in urine after consumption of either
      broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl
      epicatechin concentrations increased dramatically after consumption of
      raspberries. CONCLUSIONS: This biomarker lead discovery strategy can identify
      urinary metabolites associated with acute exposure to individual foods. Future
      studies are required to validate the specificity and utility of potential
      biomarkers in an epidemiologic context.

PMID- 21865329
TI  - Dietary fat and breast cancer: comparison of results from food diaries and food
      frequency questionnaires in the UK Dietary Cohort Consortium.
AB  - BACKGROUND: Epidemiologic studies of dietary fat and breast cancer risk are
      inconsistent, and it has been suggested that a true relation may have been
      obscured by the imprecise measurement of fat intake. OBJECTIVE: We examined
      associations of fat with breast cancer risk by using estimates of fat intake from
      food diaries and food-frequency questionnaires (FFQs) pooled from 4 prospective
      studies in the United Kingdom. DESIGN: A total of 657 cases of breast cancer in
      premenopausal and postmenopausal women were matched on study, age, and
      recruitment date with 1911 control subjects. Nutrient intakes were estimated from
      food diaries and FFQs. Conditional logistic regression was used to estimate ORs
      for breast cancer associated with total, saturated, monounsaturated, and
      polyunsaturated fat intakes with adjustment for relevant covariates. RESULTS:
      Neither the food diaries nor the FFQs showed any positive associations between
      fat intake and overall breast cancer risk. ORs (95% CIs) for the highest compared
      with lowest quintiles of percentage of energy from total fat were 0.90 (0.66,
      1.23) for food diaries and 0.80 (0.59, 1.09) for FFQs. CONCLUSION: In this study,
      breast cancer risk was not associated with fat intake in middle-aged women in the
      United Kingdom, irrespective of whether diet was measured by food diaries or by
      FFQs.

PMID- 21865331
TI  - Effect of lectin-like oxidized LDL receptor-1 polymorphism on liver disease,
      glucose homeostasis, and postprandial lipoprotein metabolism in nonalcoholic
      steatohepatitis.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) affects 3-5% of the general adult
      population and predisposes to cirrhosis, cardiovascular disease (CVD), and
      diabetes through unclear mechanisms. Lectin-like oxidized LDL receptor-1 (LOX-1)
      has been connected to CVD risk in the general population and to insulin
      resistance and hepatic fibrogenesis in experimental models. OBJECTIVE: The
      objective was to assess the effect of the common functional LOX-1 IVS4-14 A->G
      polymorphism on liver disease, adipokines, oxidative stress, lipoprotein
      metabolism, and glucose homeostasis in NASH. DESIGN: Forty nonobese, nondiabetic,
      normolipidemic biopsy-proven NASH patients and 40 age-, sex-, BMI-, and LOX-1
      IVS4-14 A->G polymorphism--matched healthy control subjects underwent an oral-fat
      load test (OFT), with measurement of plasma triglyceride-rich lipoprotein (TRLP)
      subfractions, oxidized LDL, total antioxidant status (TAS), adipokines (resistin
      and adiponectin), and cytokeratin-18 fragments (marker of hepatocyte apoptosis).
      The subjects also underwent an oral-glucose-tolerance test (OGTT), with minimal
      model analysis to yield variables of glucose homeostasis. RESULTS: The LOX-1
      polymorphism was independently associated with liver histology (G allele carriers
      had more severe liver disease); during the OFT, the G allele was associated with
      small TRLP accumulation, lower TAS, adipokine imbalance (higher resistin and
      lower adiponectin), and increased cytokeratin-18 fragments. The G allele was also
      independently associated with insulin resistance, impaired pancreatic beta cell
      function, and incretin effect during the OGTT. CONCLUSION: In NASH, the LOX-1
      polymorphism is associated with liver disease severity and may predispose to CVD
      through modulation of postprandial small TRLPs and adipokine balance and to
      diabetes by affecting both insulin secretion and insulin sensitivity.

PMID- 21865332
TI  - Zinc absorption and zinc status are reduced after Roux-en-Y gastric bypass: a
      randomized study using 2 supplements.
AB  - BACKGROUND: Micronutrient deficiencies are common in patients undergoing gastric
      bypass. The effect of this type of surgery on zinc absorption and zinc status is
      not well known. OBJECTIVE: The objective was to evaluate the effects of Roux-en-Y
      gastric bypass (RYGBP) on zinc status and zinc absorption at different stages
      after surgery. We hypothesized that zinc status would be significantly impaired
      after surgery and that this impairment would be less severe in subjects receiving
      increased supplemental zinc. We also hypothesized that zinc absorption would be
      lower after surgery. DESIGN: Anthropometric and body-composition variables and
      dietary and biochemical indexes of zinc status and zinc absorption were
      determined in 67 severe and morbidly obese women [mean (+/-SD) age: 36.9 +/- 9.8
      y; BMI (in kg/m(2)): 45.2 +/- 4.7] who underwent RYGBP. The subjects were
      randomly assigned to 1 of 2 vitamin-mineral supplementation groups. Measurements
      were made before and 6, 12, and 18 mo after surgery. Fifty-six subjects completed
      the 18-mo follow-up. RESULTS: Mean plasma zinc, erythrocyte membrane alkaline
      phosphatase activity, and the size of the rapidly exchangeable zinc pool
      decreased after RYGBP. Percentage zinc absorption decreased significantly from
      32.3% to 13.6% at 6 mo after RYGBP and to 21% at 18 mo after surgery. No effect
      of supplement type was observed. CONCLUSIONS: Zinc status is impaired after
      RYGBP, despite the finding that dietary plus supplemental zinc doubled
      recommended zinc intakes in healthy persons. Zinc absorption capacity is
      significantly reduced soon after RYGBP, with no major changes until 18 mo after
      surgery.

PMID- 21865333
TI  - Zinc homeostasis and gut function in children with celiac disease.
AB  - BACKGROUND: Celiac disease (CD) is an immunologic enteropathy triggered by the
      intake of gluten. It is thought that the enteropathy impairs gut function and
      absorption. OBJECTIVE: We assessed the zinc-absorption capacity and small-bowel
      integrity in children with CD. DESIGN: Children in whom a diagnosis of CD was
      considered clinically and either confirmed (n = 16; Marsh score >=3) or not (n =
      22; Marsh score of 0) with a small-bowel biopsy (SBB) were recruited. The
      fractional absorption of zinc (FAZ) was determined by the administration of an
      oral (67)Zn dose (2.5 mg) and an intravenous (70)Zn dose (0.2 mg) 2 h before and
      during the SBB, respectively. Spot urine samples were collected, and zinc
      isotopic ratios were determined by ion-coupled plasma mass spectrometry. Gut
      health was assessed by the ingestion of (13)C-sucrose (20 g) after an overnight
      fast, and breath samples were collected and analyzed by isotope ratio mass
      spectrometry. RESULTS: There was no difference in FAZ between children with a
      Marsh score >=3 (mean +/- SEM: 0.68 +/- 0.05) and children with a Marsh score of
      0 (0.74 +/- 0.05). The exchangeable zinc pool (EZP) was significantly (P < 0.05)
      lower in children with a Marsh score >=3 (2.6 +/- 0.8 mg/kg) than in children
      with a Marsh score of 0 (3.8 +/- 1.4 mg/kg). Gut function in children with a
      Marsh score >=3 (4.5 +/- 0.7% cumulative dose recovered at 90 min) was lower than
      the lower cutoff of a normal gut-function breath test (5.06% cumulative dose
      recovered at 90 min) but not significantly different from that in children with a
      Marsh score of 0 (4.9 +/- 0.4%). There was a significant (P < 0.01) correlation
      between zinc absorption and gut function in children with CD. CONCLUSIONS: Zinc
      absorption did not appear below usual amounts in subjects with CD. Children with
      CD have impaired gut function that may affect their zinc nutritional status as
      shown by a smaller EZP. However, the EZP decrease in children with CD was not
      compared with that in healthy control subjects, and its biological meaning is
      uncertain.

PMID- 21865334
TI  - Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial
      stiffness: a randomized controlled trial.
AB  - BACKGROUND: The dietary intake of n-3 (omega-3) long-chain PUFAs (LC-PUFAs) from
      fish may improve endothelial function and arterial stiffness. OBJECTIVE: The
      objective was to test the hypothesis that increasing intakes of n-3 LC-PUFAs
      equivalent to the consumption of 1, 2, or 4 portions of oily fish per week
      favorably affects endothelial function and arterial stiffness. DESIGN: A parallel
      design, randomized, double-blind study compared daily doses of 0.45, 0.9, and 1.8
      g n-3 LC-PUFAs (EPA:DHA ratio of 1.51:1) with placebo (refined olive oil). The
      primary and secondary outcomes were changes in flow-mediated dilatation (FMD) of
      the brachial artery, arterial stiffness, and blood pressure. Nonsmoking men (n =
      142) and women (n = 225) aged 45-70 y were randomly assigned to treatment for 12
      mo; 312 subjects completed the intervention. RESULTS: Compliance with the
      intervention was corroborated by significant dose-dependent increases in the
      proportions of EPA and DHA in erythrocyte lipids and a 16.5% reduction in serum
      triacylglycerol concentrations with 1.8 g n-3 LC-PUFAs/d. FMD was lower in men
      than in women (P < 0.0001) and decreased with age (rho = 0.270, P < 0.001) but
      was not significantly (P = 0.781) related to n-3 LC-PUFA intake. The mean changes
      in FMD (95% CIs) compared with placebo were 0.1% (-0.9%, 1.1%), -0.3% (-1.3%,
      0.6%), and -0.3% (-1.3%, 0.7%) with daily intakes of 0.45, 0.9, and 1.8 g n-3 LC
      PUFAs, respectively. No significant treatment effects were noted for arterial
      stiffness and central mean or 24-h ambulatory blood pressure. CONCLUSION: Intakes
      of n-3 LC-PUFAs <=1.8 g/d do not improve endothelial function in healthy adults.
      The trial is registered at controlled-trials.com as ISRCTN66664610.

PMID- 21865335
TI  - Phylogenetic nomenclature, three-taxon statements, and unnecessary name changes.

PMID- 21865336
TI  - Branch lengths on birth-death trees and the expected loss of phylogenetic
      diversity.
AB  - Diversification is nested, and early models suggested this could lead to a great
      deal of evolutionary redundancy in the Tree of Life. This result is based on a
      particular set of branch lengths produced by the common coalescent, where pendant
      branches leading to tips can be very short compared with branches deeper in the
      tree. Here, we analyze alternative and more realistic Yule and birth-death
      models. We show how censoring at the present both makes average branches one half
      what we might expect and makes pendant and interior branches roughly equal in
      length. Although dependent on whether we condition on the size of the tree, its
      age, or both, these results hold both for the Yule model and for birth-death
      models with moderate extinction. Importantly, the rough equivalency in interior
      and exterior branch lengths means that the loss of evolutionary history with loss
      of species can be roughly linear. Under these models, the Tree of Life may offer
      limited redundancy in the face of ongoing species loss.

PMID- 21865337
TI  - Dispersal between shallow and abyssal seas and evolutionary loss and regain of
      compound eyes in cylindroleberidid ostracods: conflicting conclusions from
      different comparative methods.
AB  - Complex organs such as eyes are commonly lost during evolution, but the timescale
      on which lost phenotypes could be reactivated is a matter of long-standing
      debate, with important implications for the molecular mechanisms of trait loss.
      Two phylogenetic approaches have been used to test whether regain of traits has
      occurred. One way is by comparison of nested, continuous-time Markov models of
      trait evolution, approaches that we term tree-based tests. A second way to
      demonstrate statistical support for trait regain is through use of node-based
      tests that employ explicit estimation of ancestral node states. Here, we estimate
      new molecular and morphological phylogenies and use them to examine the
      possibility of eye regain and dispersal between abyssal and shallow seas during
      the history of cylindroleberidid ostracods, a family of about 200 species,
      comprising both eyeless and sighted species. First, we confirmed that eye
      presence/absence is correlated with habitat depth. Parameter estimates from a
      phylogenetic model indicate that speciation is more rapid in deep-sea eyeless
      clades compared with shallow-water sighted clades. In addition, we found that
      tree-based statistical tests usually indicated reversals, including both
      transitions from deep to shallow seas and regain of eyes. In contrast, node-based
      statistical tests usually failed to show significant support for reversals. These
      results also hold for simulated phylogenies, indicating that they are not unique
      to the current data set. We recommend that both tree-based and node-based tests
      should be examined before making conclusions about character reversal and that
      ideally, alternative character histories should be tested using additional data,
      besides just the phylogenetic distribution of presence/absence of the characters.

PMID- 21865338
TI  - Tree models for macroevolution and phylogenetic analysis.
AB  - It has long been recognized that phylogenetic trees are more unbalanced than
      those generated by a Yule process. Recently, the degree of this imbalance has
      been quantified using the large set of phylogenetic trees available in the
      TreeBASE data set. In this article, a more precise analysis of imbalance is
      undertaken. Trees simulated under a range of models are compared with trees from
      TreeBASE and two smaller data sets. Several simple models can match the amount of
      imbalance measured in real data. Most of them also match the variance of
      imbalance among empirical trees to a remarkable degree. Statistics are developed
      to measure balance and to distinguish between trees with the same overall
      imbalance. The match between models and data for these statistics is
      investigated. In particular, age-dependent (Bellman-Harris) branching process are
      studied in detail. It remains difficult to separate the process of macroevolution
      from biases introduced by sampling. The lessons for phylogenetic analysis are
      clearer. In particular, the use of the usual proportional to distinguishable
      arrangements (uniform) prior on tree topologies in Bayesian phylogenetic analysis
      is not recommended.

PMID- 21865339
TI  - Contribution of motion parallax to segmentation and depth perception.
AB  - Relative image motion resulting from active movement of the observer could
      potentially serve as a powerful perceptual cue, both for segmentation of object
      boundaries and for depth perception. To examine the perceptual role of motion
      parallax from shearing motion, we measured human performance in three
      psychophysical tasks: segmentation, depth ordering, and depth magnitude
      estimation. Stimuli consisted of random dot textures that were synchronized to
      head movement with sine- or square-wave modulation patterns. Segmentation was
      assessed with a 2AFC orientation judgment of a motion-defined boundary. In the
      depth-ordering task, observers reported which modulation half-cycle appeared in
      front of the other. Perceived depth magnitude was matched to that of a 3D
      rendered image with multiple static cues. The results indicate that head movement
      might not be important for segmentation, even though it is crucial for obtaining
      depth from motion parallax--thus, concomitant depth perception does not appear to
      facilitate segmentation. Our findings suggest that segmentation works best for
      abrupt, sharply defined motion boundaries, whereas smooth gradients are more
      powerful for obtaining depth from motion parallax. Thus, motion parallax may
      contribute in a different manner to segmentation and to depth perception and
      suggests that their underlying mechanisms might be distinct.

PMID- 21865340
TI  - Necker cube: stimulus-related (low-level) and percept-related (high-level) EEG
      signatures early in occipital cortex.
AB  - During observation of an ambiguous Necker cube, our percept changes spontaneously
      although the external stimulus does not. An EEG paradigm allowing time-resolved
      EEG measurement during endogenous perceptual reversals recently revealed a chain
      of ERP correlates beginning with an early occipital positivity at around 130 ms
      (Reversal Positivity, "RP"). In order to better understand the functional role of
      this RP, we investigated its relation to the P100, which is spatiotemporally
      close, typically occurring 100 ms after onset of a visual stimulus at occipital
      electrodes. We compared the relation of the ERP amplitudes to varying sizes of
      ambiguous Necker cubes. The main results are: (1) The P100 amplitude increases
      monotonically with stimulus size but is independent of the participants' percept.
      (2) The RP, in contrast, is percept-related and largely unaffected by stimulus
      size. (3) A similar pattern to RP was found for reaction times: They depend on
      the percept but not on stimulus size. We speculate that the P100 reflects
      processing of elementary visual features, while the RP is related to a processing
      conflict during 3D interpretation that precedes a reversal. The present results
      indicate that low-level visual processing (related to stimulus size) and
      (relative) high-level processing (related to perceptual reversal) occur in close
      spatial and temporal vicinity.

PMID- 21865341
TI  - Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL).
AB  - Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas.
      Nevertheless, diagnosis of early disease has proven difficult because of a
      clinical and histologic resemblance to benign inflammatory skin diseases. To
      address whether microRNA (miRNA) profiling can discriminate CTCL from benign
      inflammation, we studied miRNA expression levels in 198 patients with CTCL,
      peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and
      dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b,
      and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from
      benign skin diseases with > 90% accuracy in a training set of 90 samples and a
      test set of 58 blinded samples. These miRNAs also distinguish malignant and
      benign lesions in an independent set of 50 patients with PTL and skin
      inflammation and in experimental human xenograft mouse models of psoriasis and
      CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin
      disorders validates differential expression of 4 of the 5 miRNAs and confirms
      previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR
      155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high
      specificity and sensitivity, and with a classification accuracy of 95%,
      indicating that miRNAs have a high diagnostic potential in CTCL.

PMID- 21865342
TI  - Impaired FcepsilonRI stability, signaling, and effector functions in murine mast
      cells lacking glycosylphosphatidylinositol-anchored proteins.
AB  - A key event and potential therapeutic target in allergic and asthmatic diseases
      is signaling by the IgE receptor FcepsilonRI, which depends on its interactions
      with Src family kinases (SFK). Here we tested the hypothesis that
      glycosylphosphatidylinositiol-anchored proteins (GPI-AP) are involved in
      FcepsilonRI signaling, based on previous observations that GPI-AP colocalize with
      and mediate activation of SFK. We generated mice with a hematopoietic cell
      specific GPI-AP deficiency by targeted disruption of the GPI biosynthesis gene
      PigA. In these mice, IgE-mediated passive cutaneous anaphylaxis was largely
      abolished. PigA-deficient mast cells cultured from these mice showed impaired
      degranulation in response to stimulation with IgE and antigen in vitro, despite
      normal IgE binding and antigen-induced FcepsilonRI aggregation. On stimulation of
      these cells with IgE and antigen, coprecipitation of the FcepsilonRI alpha-chain
      with the gamma-chain and beta-chain was markedly reduced. As a result,
      IgE/antigen-induced FcepsilonRI-Lyn association and gamma-chain tyrosine
      phosphorylation were both impaired in PigA-deficient cells. These data provide
      genetic evidence for an unanticipated key role of GPI-AP in FcepsilonRI
      interchain interactions and early FcepsilonRI signaling events, necessary for
      antigen-induced mast cell degranulation.

PMID- 21865343
TI  - ZAP-70 enhances migration of malignant B lymphocytes toward CCL21 by inducing
      CCR7 expression via IgM-ERK1/2 activation.
AB  - ZAP-70 in chronic lymphocytic leukemia (CLL) has been associated with enhanced B
      cell receptor (BCR) signaling, survival, and migration. We investigated whether
      ZAP-70 can directly govern migration and the underlying mechanisms. In the ZAP-70
      stably transfected Ramos cell line, IgM stimulation, but no IgD, enhanced
      phosphorylation of ERK1/2, Akt and Syk, and delayed IgM and CD79b
      internalization. In contrast, in the Raji cell line, where ZAP-70 was
      constitutively phosphorylated, ERK1/2, but not Akt, was phosphorylated,
      suggesting that MAPK pathway mediates ZAP-70 effects. BCR stimulation modulated
      the expression of CCR7, CXCR4, CXCR5, CD44, CD49d, and CD62L, which were up
      regulated in ZAP-70-positive CLL primary subclones. The most dramatic change
      after BCR engagement in ZAP-70-transfected cells was CCR7 up-regulation, this
      being impaired by ERK1/2 inhibition and translating into both increased signaling
      and migration toward CCL21. Primary CLL subclones with high ZAP-70 expression
      showed increased migration toward CCL21. In conclusion, ZAP-70 ectopic expression
      led to enhanced BCR signaling after IgM stimulation and increased the expression
      of CCR7 predominantly via ERK1/2, increasing the response and migration toward
      CCL21. In primary CLL samples, cellular subsets with high ZAP-70 expression had
      increased expression of adhesion molecules and chemokine receptors in addition to
      an enhanced ability to migrate toward CCL21.

PMID- 21865344
TI  - Ontogeny stage-independent and high-level clonal expansion in vitro of mouse
      hematopoietic stem cells stimulated by an engineered NUP98-HOX fusion
      transcription factor.
AB  - Achieving high-level expansion of hematopoietic stem cells (HSCs) in vitro will
      have an important clinical impact in addition to enabling elucidation of their
      regulation. Here, we couple the ability of engineered NUP98-HOXA10hd expression
      to stimulate > 1000-fold net expansions of murine HSCs in 10-day cultures
      initiated with bulk lin(-)Sca-1(+)c-kit(+) cells, with strategies to purify fetal
      and adult HSCs and analyze their expansion clonally. We find that NUP98-HOXA10hd
      stimulates comparable expansions of HSCs from both sources at ~ 60% to 90% unit
      efficiency in cultures initiated with single cells. Clonally expanded HSCs
      consistently show balanced long-term contributions to the lymphoid and myeloid
      lineages without evidence of leukemogenic activity. Although effects on fetal and
      adult HSCs were indistinguishable, NUP98-HOXA10hd-transduced adult HSCs did not
      thereby gain a competitive advantage in vivo over freshly isolated fetal HSCs.
      Live-cell image tracking of single transduced HSCs cultured in a microfluidic
      device indicates that NUP98-HOXA10hd does not affect their proliferation
      kinetics, and flow cytometry confirmed the phenotype of normal proliferating HSCs
      and allowed reisolation of large numbers of expanded HSCs at a purity of 25%.
      These findings point to the effects of NUP98-HOXA10hd on HSCs in vitro being
      mediated by promoting self-renewal and set the stage for further dissection of
      this process.

PMID- 21865345
TI  - Clonal drift demonstrates unexpected dynamics of the T-cell repertoire in T-large
      granular lymphocyte leukemia.
AB  - T-cell large granular lymphocyte leukemia (T-LGLL) is characterized by chronic
      lymphoproliferation of cytotoxic T lymphocytes (CTLs) and is associated with
      lineage-restricted cytopenias. Introduction of T-cell receptor (TCR) variable
      beta-chain (Vbeta) monoclonal antibodies has facilitated identification and
      enumeration of clonal CTLs by flow cytometry. A highly skewed TCR Vbeta
      repertoire identified by flow cytometry is strongly associated with monoclonal
      CDR3 regions by quantitative sequencing and positive TCRgamma rearrangement
      assays. Therefore, Vbeta expansions can serve as surrogate markers of CTL
      clonality to assess clonal kinetics in T-LGLL. We analyzed the TCR repertoire in
      143 patients, 71 of which were available for serial measurements over 6 to 96
      months. Although the majority (38/71, 54%) maintained a consistent monoclonal
      expansion, many (26/71, 37%) unexpectedly displayed a change in the dominant
      clone, whereby the original CTL clone contracted and another emerged as
      demonstrated by Vbeta typing. Our results demonstrate that the T-cell repertoire
      is more dynamic in T-LGLL than recognized previously, illustrating the
      heterogeneity of disorders under this categorization.

PMID- 21865347
TI  - An improved method on stimulated T-lymphocytes to functionally characterize novel
      and known LDLR mutations.
AB  - The main causes of familial hypercholesterolemia (FH) are mutations in LDL
      receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR
      function impairment caused by mutations and would be useful as a diagnostic tool
      if they allow discrimination between FH patients and controls. In order to
      identify the best method to detect LDLR activity, we compared continuous Epstein
      Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes.
      In addition, we characterized both novel and known mutations in the LDLR gene. T
      lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood
      of 24 FH patients and 24 control subjects. Functional assays were performed by
      incubation with fluorescent LDL followed by flow cytometry analysis. Residual
      LDLR activity was calculated normalizing fluorescence for the mean fluorescence
      of controls. With stimulated T-lymphocytes we obtained a better discrimination
      capacity between controls and FH patients compared with EBV-transformed B
      lymphocytes as demonstrated by receiver operating characteristic (ROC) curve
      analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001
      both). The characterization of LDLR activity through T-lymphocytes is more simple
      and faster than the use of EBV-transformed B-lymphocytes and allows a complete
      discrimination between controls and FH patients. Therefore the evaluation of
      residual LDLR activity could be helpful not only for mutation characterization
      but also for diagnostic purposes.

PMID- 21865346
TI  - Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia
      chromosome-positive chronic myeloid leukemia patients with resistance or
      intolerance to imatinib.
AB  - Bosutinib, a dual Src/Abl kinase inhibitor, has shown potent activity against
      chronic myeloid leukemia (CML). In this phase 1/2 study we evaluated bosutinib in
      patients with chronic phase imatinib-resistant or imatinib-intolerant CML. Part 1
      was a dose-escalation study to determine the recommended starting dose for part
      2; part 2 evaluated the efficacy and safety of bosutinib 500 mg once-daily
      dosing. The study enrolled 288 patients with imatinib-resistant (n = 200) or
      imatinib-intolerant (n = 88) CML and no other previous kinase inhibitor exposure.
      At 24 weeks, 31% of patients achieved major cytogenetic response (primary end
      point). After a median follow-up of 24.2 months, 86% of patients achieved
      complete hematologic remission, 53% had a major cytogenetic response (41% had a
      complete cytogenetic response), and 64% of those achieving complete cytogenetic
      response had a major molecular response. At 2 years, progression-free survival
      was 79%; overall survival at 2 years was 92%. Responses were seen across Bcr-Abl
      mutants, except T315I. Bosutinib exhibited an acceptable safety profile; the most
      common treatment-emergent adverse event was mild/moderate, typically self
      limiting diarrhea. Grade 3/4 nonhematologic adverse events (> 2% of patients)
      included diarrhea (9%), rash (9%), and vomiting (3%). These data suggest
      bosutinib is effective and tolerable in patients with chronic phase imatinib
      resistant or imatinib-intolerant CML. This trial was registered at
      http://www.clinicaltrials.gov as NCT00261846.

PMID- 21865348
TI  - BSSL and PLRP2: key enzymes for lipid digestion in the newborn examined using the
      Caco-2 cell line.
AB  - In rodents, bile salt-stimulated lipase (BSSL) and pancreatic lipase-related
      protein 2 (PLRP2) are the dominant lipases expressed in the exocrine pancreas in
      early life when milk is the main food. The aim of the present study was to
      evaluate whether BSSL and PLRP2 are also key enzymes in neonatal intestinal fat
      digestion. Using Caco-2 cells as a model for the small intestinal epithelium,
      purified human enzymes were incubated in the apical compartment with substrates,
      bile salt composition and concentrations physiologic to newborn infants. Both
      BSSL and PLRP2 hydrolyzed triglycerides (TG) to free FA and glycerol. Released FA
      were absorbed by the cells and reesterfied to TG. Together, BSSL and PLRP2 had a
      synergistic effect, increasing cellular uptake and reesterification 4-fold
      compared with the sum of each lipase alone. A synergistic effect was also
      observed with retinyl ester as a substrate. PLRP2 hydrolyzed cholesteryl ester
      but not as efficiently as BSSL, and the two had an additive rather than
      synergistic effect. We conclude the key enzymes in intestinal fat digestion are
      different in newborns than later in life. Further studies are needed to fully
      understand this difference and its implication for designing optimal neonatal
      nutrition.

PMID- 21865349
TI  - Detailed analysis of mucosal herpes simplex virus-2 replication kinetics with and
      without antiviral therapy.
AB  - OBJECTIVES: The presence of herpes simplex virus-2 (HSV-2) shedding episodes
      correlates with transmission to sexual partners and neonates, and some episodes
      correlate with disease manifestations. HSV-2-targeted guanosine analogues are
      effective when given on a prophylactic basis, but do not completely eliminate
      recurrences, asymptomatic shedding or transmission. We sought to describe the
      impact of twice-daily aciclovir and famciclovir on shedding episodes. METHODS: We
      used pooled results from crossover clinical trials to construct frequency
      histograms for viral shedding episode duration, peak copy number, expansion
      kinetics and decay kinetics. RESULTS: Suppressive aciclovir and famciclovir
      decreased the frequency of episodes of >24 h duration by 50%, lowered the mean
      early episode expansion rate (from 8.2 to 7.2 HSV DNA logs/day, P = 0.004),
      decreased the mean peak values for shedding episodes (from 4.9 to 3.9 log(10) HSV
      DNA copies/mL, P < 0.001) and lowered the mean episode duration (from 4.8 to 2.1
      days, P < 0.001) primarily by decreasing the probability of viral re-expansion
      during episodes. The mean rate of late viral decay was similar for persons on and
      off antiviral medications (-6.0 versus -5.8 HSV DNA logs/day, P = 0.61).
      CONCLUSIONS: HSV-2-targeted antiviral therapy limits episode severity by
      decreasing the rate of early viral expansion and the likelihood of episode re
      expansion. Late clearance of episodes in the immunocompetent host is not affected
      by antiviral therapy, suggesting that local immune response is critical for
      clearance of episodes both on and off treatment.

PMID- 21865350
TI  - Delineation of key regulatory elements identifies points of vulnerability in the
      mitogen-activated signaling network.
AB  - Drug development efforts against cancer are often hampered by the complex
      properties of signaling networks. Here we combined the results of an RNAi screen
      targeting the cellular signaling machinery, with graph theoretical analysis to
      extract the core modules that process both mitogenic and oncogenic signals to
      drive cell cycle progression. These modules encapsulated mechanisms for
      coordinating seamless transition of cells through the individual cell cycle
      stages and, importantly, were functionally conserved across different cancer cell
      types. Further analysis also enabled extraction of the core signaling axes that
      progressively guide commitment of cells to the division cycle. Importantly,
      pharmacological targeting of the least redundant nodes in these axes yielded a
      synergistic disruption of the cell cycle in a tissue-type-independent manner.
      Thus, the core elements that regulate temporally distinct stages of the cell
      cycle provide attractive targets for the development of multi-module-based
      chemotherapeutic strategies.

PMID- 21865351
TI  - Energy deprivation alters in a leptin- and cortisol-independent manner
      circulating levels of activin A and follistatin but not myostatin in healthy
      males.
AB  - CONTEXT: Activin A, myostatin, and follistatin have recently emerged as important
      regulatory molecules of reproduction and the musculoskeletal system. Little is
      known, however, about their day/night patterns of secretion and their
      physiological regulation by energy availability. OBJECTIVE: The objective of the
      study was to explore day/night patterns of secretion and assess whether energy
      deprivation alters circulating levels of activin A, myostatin, follistatin, and
      cortisol and to examine whether leptin may mediate this effect. DESIGN, SETTING
      AND PATIENTS, AND INTERVENTIONS: Seven healthy lean men (aged 23.2 +/- 3.7 yr,
      body mass index 23.6 +/- 1.7 kg/m(2)) were studied for 72 h under three different
      conditions: on their baseline/isocaloric diet and in a complete fasting state
      with administration of either placebo or metreleptin. The two fasting studies
      were randomized and double blinded. Blood samples were obtained every 15 min from
      0800 h on d 3 until 0800 h on d 4 and pooled hourly. MAIN OUTCOME MEASURES: Serum
      concentrations of activin A, myostatin, follistatin, cortisol, and leptin were
      measured. RESULTS: In contrast to cortisol, we demonstrated no day/night pattern
      of activin A, myostatin, and follistatin secretion. Activin A concentrations
      decreased significantly in response to energy deprivation (P < 0.01). Follistatin
      and cortisol concentrations increased significantly (P < 0.01 and P < 0.01,
      respectively). Myostatin remained unaffected (P = 0.40). Leptin administration
      reversed cortisol response (P < 0.01) but failed to alter activin A, follistatin,
      or myostatin concentrations. CONCLUSIONS: Unlike cortisol, there is no day/night
      variation in the concentrations of activin A, myostatin, and follistatin in
      healthy young males. Although energy deprivation-induced cortisol changes are
      leptin mediated, the changes in follistatin and activin A concentrations occur
      through a leptin-independent pathway.

PMID- 21865352
TI  - A randomized pilot study of monthly cycled testosterone replacement or continuous
      testosterone replacement versus placebo in older men.
AB  - CONTEXT: Cycling androgens has been reported by athletes to improve physical
      performance by enhancing muscle mass and strength, a paradigm that has not been
      studied, and may have clinical value in older men being treated with
      testosterone. OBJECTIVE: We investigated the efficacy of a monthly cycled
      testosterone regimen that uses half the testosterone dose as the current standard
      of care continuous therapy on body composition and muscle strength in older men.
      DESIGN, SETTING, AND PATIENTS: Twenty-four community-dwelling older men 70 +/- 2
      yr of age with total testosterone levels below 500 ng/dl were randomized at the
      Institute for Translational Sciences-Clinical Research Center into a 5-month
      double-blind placebo-controlled trial. INTERVENTION: Subjects were dosed weekly
      for 5 months, receiving continuous testosterone (TE, n = 8; 100 mg testosterone
      enanthate, im injection), monthly cycled testosterone (MO, n = 8; alternating
      months of testosterone and placebo), or placebo (PL, n = 8). MAIN OUTCOME
      MEASURES: Main outcomes included body composition by dual-energy x-ray
      absorptiometry and upper and lower body muscle strength. Secondary outcomes
      included body weight, serum hormones, and mixed-muscle protein fractional
      synthesis rate (FSR). RESULTS: Total lean body mass was increased and percent fat
      was reduced after 5 months in TE and MO (P < 0.05). Upper body muscle strength
      increased in TE, and lower body muscle strength increased in TE and MO (P <
      0.05). FSR increased in TE and MO (P < 0.05) but not in PL. CONCLUSIONS: Cycled
      testosterone improved body composition and increased muscle strength compared
      with placebo and increased FSR similarly to continuous testosterone.

PMID- 21865353
TI  - In silico analysis identifies a novel role for androgens in the regulation of
      human endometrial apoptosis.
AB  - CONTEXT: The endometrium is a multicellular, steroid-responsive tissue that
      undergoes dynamic remodeling every menstrual cycle in preparation for
      implantation and, in absence of pregnancy, menstruation. Androgen receptors are
      present in the endometrium. OBJECTIVE: The objective of the study was to
      investigate the impact of androgens on human endometrial stromal cells (hESC).
      DESIGN: Bioinformatics was used to identify an androgen-regulated gene set and
      processes associated with their function. Regulation of target genes and impact
      of androgens on cell function were validated using primary hESC. SETTING: The
      study was conducted at the University Research Institute. PATIENTS: Endometrium
      was collected from women with regular menses; tissues were used for recovery of
      cells, total mRNA, or protein and for immunohistochemistry. RESULTS: A new
      endometrial androgen target gene set (n = 15) was identified. Bioinformatics
      revealed 12 of these genes interacted in one pathway and identified an
      association with control of cell survival. Dynamic androgen-dependent changes in
      expression of the gene set were detected in hESC with nine significantly down
      regulated at 2 and/or 8 h. Treatment of hESC with dihydrotestosterone reduced
      staurosporine-induced apoptosis and cell migration/proliferation. CONCLUSIONS:
      Rigorous in silico analysis resulted in identification of a group of androgen
      regulated genes expressed in human endometrium. Pathway analysis and functional
      assays suggest androgen-dependent changes in gene expression may have a
      significant impact on stromal cell proliferation, migration, and survival. These
      data provide the platform for further studies on the role of circulatory or local
      androgens in the regulation of endometrial function and identify androgens as
      candidates in the pathogenesis of common endometrial disorders including
      polycystic ovarian syndrome, cancer, and endometriosis.

PMID- 21865355
TI  - Continuation of amiodarone delays restoration of euthyroidism in patients with
      type 2 amiodarone-induced thyrotoxicosis treated with prednisone: a pilot study.
AB  - CONTEXT: Type 2 amiodarone-induced thyrotoxicosis (AIT) is a destructive
      thyroiditis usually responsive to glucocorticoids. Whether continuation of
      amiodarone affects treatment outcome is unsettled. OBJECTIVE: The objective of
      the study was to compare the outcome of glucocorticoid treatment in type 2 AIT
      patients who continued or withdrew amiodarone. DESIGN: This was a matched
      retrospective cohort study. SETTING: The study was conducted at a university
      center. PATIENTS: Eighty-three consecutive patients with untreated type 2 AIT
      participated in the study. After matching with patients continuing amiodarone
      (AMIO-ON, n = 8), patients interrupting amiodarone were randomly selected in a
      4:1 ratio (AMIO-OFF, n = 32). INTERVENTION: All patients were treated with oral
      prednisone. Patients whose thyrotoxicosis recurred after glucocorticoid
      withdrawal were treated with a second course of prednisone. MAIN OUTCOME MEASURE:
      Time and rate of cure were measured. RESULTS: Median time to the first
      normalization of serum thyroid hormone levels did not significantly differ in
      AMIO-ON and AMIO-OFF patients (24 and 31 d, respectively; P = 0.326). Conversely,
      median time for stably restoring euthyroidism was 140 d in AMIO-ON patients and
      47 d in AMIO-OFF patients (log rank, P = 0.011). In fact, AIT recurred in five of
      seven AMIO-ON patients (71.4%) and in only three of 32 AMIO-OFF patients (9.4%, P
      = 0.002), requiring readministration of prednisone. One AMIO-ON patient never
      reached thyroid hormone normalization during the study period. Factors associated
      with glucocorticoid failure were thyroid volume and amiodarone continuation.
      CONCLUSIONS: Prednisone restores euthyroidism in most type 2 AIT patients,
      irrespective of amiodarone continuation or withdrawal. However, continuing
      amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in
      the stable restoration of euthyroidism and a longer exposure of the heart to
      thyroid hormone excess.

PMID- 21865356
TI  - Facing the nuclear threat: thyroid blocking revisited.
AB  - CONTEXT: People being exposed to potentially harmful amounts of radioactive
      iodine need prophylaxis to prevent high radiation-absorbed doses to the thyroid.
      OBJECTIVE: Parameters determining the individual protective effect of a
      pharmacological intervention were investigated. DESIGN AND PARTICIPANTS:
      Biokinetics of (123)I was evaluated in 27 healthy volunteers (aged 22-46 yr,
      median 25 yr, in total 48 assessments) twice in a baseline measurement of the
      undisturbed kinetics and in an intervention assessment 48 h later. INTERVENTIONS:
      Seven regimens using single doses of potassium iodide (KI) or sodium perchlorate
      (SP) at different times relative to exposure were compared: 100 mg KI (-24, 2, 8,
      24 h), 100 mg SP (2 h), or 1 g SP (2, 8 h). MAIN OUTCOME MEASURES: Different
      drugs and dosages and the influence of individual parameters of iodine kinetics
      should be tested. RESULTS: Mean dose reductions for interventions at -24, 2, 8,
      and 24 h relative to the activity incorporation were 88.7, 59.7, 25.4, and 2.8%,
      respectively. One gram SP was equally effective as 100 mg KI; residual uptake was
      observed after 100 mg SP. The individual dose reduction decreased exponentially
      with the effective half-life of the activity in the blood. Kinetics in subjects
      older than 40 yr was as assumed in official guidelines for the prophylaxis after
      nuclear accidents but was faster in younger participants. CONCLUSIONS: Data on
      the efficacy of thyroid blocking used in the guidelines are adequate for older
      people but not for young individuals with their typically faster kinetics. SP may
      be used for thyroid blocking as alternative for individuals with iodine
      hypersensitivity.

PMID- 21865354
TI  - Early initiation of hormone therapy in menopausal women is associated with
      increased hippocampal and posterior cingulate cholinergic activity.
AB  - CONTEXT: The role of ovarian hormones in maintaining neuronal integrity and
      cognitive function is still debated. This study was undertaken to clarify the
      potential relationship between postmenopausal hormone use and the cholinergic
      system. OBJECTIVE: We hypothesized that early initiated hormone therapy (HT)
      preserves the cholinergic system and that estrogen therapy (ET) would be
      associated with higher levels of acetylcholinesterase activity in the posterior
      cingulate cortex and hippocampus compared to estrogen plus progestin therapy
      (EPT) or no HT. DESIGN AND SETTING: We conducted a cross-sectional study at a
      university teaching hospital. PATIENTS: Fifty postmenopausal women (age, 65.2 +/-
      0.7 yr) with early long-term HT (n = 34; 13 ET and 21 EPT) or no HT (n = 16)
      participated in the study. INTERVENTIONS: There were no interventions. MAIN
      OUTCOME MEASURE: We measured cholinergic activity (acetylcholinesterase) in the
      hippocampus and posterior cingulate brain regions as measured by N
      [(11)C]methylpiperidin-4-yl propionate and positron emission tomography as a
      marker of cholinergic function. RESULTS: Significant effects of treatment on
      cholinergic activity measures were obtained in the left hippocampus (F = 3.56; P
      = 0.04), right hippocampus (F = 3.42; P = 0.04), and posterior cingulate (F =
      3.76; P = 0.03). No significant effects were observed in a cortical control
      region. Post hoc testing identified greater cholinergic activity in the EPT group
      compared to the no-HT group in the left hippocampus (P = 0.048) and posterior
      cingulate (P = 0.045), with a nonstatistically significant trend in the right
      hippocampus (P = 0.073). CONCLUSIONS: A differential effect of postmenopausal ET
      and EPT on cholinergic neuronal integrity was identified in postmenopausal women.
      The findings are consistent with a preservation of cholinergic neuronal integrity
      in the EPT group.

PMID- 21865357
TI  - Measurement of mRNA transcripts of very high placental expression in maternal
      blood as biomarkers of preeclampsia.
AB  - CONTEXT: mRNA of placental origin in maternal blood shows potential as a clinical
      biomarker of obstetric diseases such as preeclampsia (PE). We hypothesized that
      mRNA transcripts very highly expressed in the placenta relative to other tissues
      will be differentially expressed in PE and be useful as mRNA biomarkers in
      maternal blood. OBJECTIVE: Our objective was to identify a panel of genes highly
      expressed in the placenta and compare their expression in placenta and maternal
      whole blood from PE vs. control pregnancies. SETTING: Placental tissue and
      maternal whole blood specimens were obtained from normotensive controls (n = 15)
      and pregnancies complicated by severe preterm PE (n = 21). INTERVENTION: mRNA
      expression was evaluated by quantitative real-time RT-PCR. RESULTS: We identified
      20 genes exhibiting highest to fourth highest expression in the placenta relative
      to all other tissues. All genes were detectable in placenta. Nine of the 20 genes
      were detectable in maternal whole blood. Four of the nine genes detectable in
      blood (i.e. PLAC3, PLAC4, CRH, and ERVWE1) were significantly increased in both
      maternal blood and placenta from PE pregnancies. The remaining five genes
      detectable in maternal blood were unchanged in both blood and placenta from PE
      pregnancies. Thus, there was complete correlation of gene expression between
      maternal blood and placenta. CONCLUSIONS: Circulating mRNA coding genes of high
      placental expression show strong correlation with transcript levels in
      preeclamptic placenta. Such transcripts may be promising candidates to screen as
      mRNA biomarkers of PE in maternal whole blood.

PMID- 21865358
TI  - Effects of simvastatin and metformin on polycystic ovary syndrome after six
      months of treatment.
AB  - CONTEXT: A randomized trial on women with polycystic ovary syndrome (PCOS)
      compared simvastatin, metformin, and a combination of these drugs. OBJECTIVE: The
      aim of the study was to evaluate long-term effects of simvastatin and metformin
      on PCOS. DESIGN: Women with PCOS (n = 139) were randomized to simvastatin (S),
      metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were
      performed at baseline and at 3 and 6 months. SETTING: The study was conducted at
      a university medical center. PRIMARY OUTCOME: We measured the change of serum
      total testosterone. RESULTS: Ninety-seven subjects completed the study. Total
      testosterone decreased significantly and comparably in all groups: by 25.6, 25.6,
      and 20.1% in the S, M, and SM groups, respectively. Both simvastatin and
      metformin improved menstrual cyclicity and decreased hirsutism, acne, ovarian
      volume, body mass index, C-reactive protein, and soluble vascular cell adhesion
      molecule-1. Dehydroepiandrosterone sulfate declined significantly only in the S
      group. Total cholesterol and low-density lipoprotein cholesterol significantly
      declined only in the S and SM groups. Ongoing reduction of ovarian volume,
      decreased hirsutism, acne and testosterone were observed between 0 and 3 months
      as well as between 3 and 6 months. Improvement of lipid profile, C-reactive
      protein, and soluble vascular cell adhesion molecule-1 occurred only during the
      first 3 months of treatment, with little change thereafter. Treatments were well
      tolerated, and no significant adverse effects were encountered. CONCLUSIONS: Long
      term treatment with simvastatin was superior to metformin. Improvement of ovarian
      hyperandrogenism continued throughout the duration of the study.

PMID- 21865359
TI  - Effect of stopping risedronate after long-term treatment on bone turnover.
AB  - CONTEXT: Determining how quickly bisphosphonate treatment effects begin to
      regress is crucial when considering termination of treatment. OBJECTIVE: Our
      objective was to assess the effects of 1 yr discontinuation of risedronate use in
      postmenopausal women with osteoporosis who had previously received risedronate
      for 2 or 7 yr. DESIGN AND SETTING: Before initiation of the current study,
      placebo/5-mg-risedronate patients had received placebo for 5 yr and risedronate
      for 2 yr, whereas 5-mg-risedronate patients had received risedronate for a total
      of 7 yr. Risedronate was then discontinued for 1 yr (yr 8). PATIENTS:
      Postmenopausal women with osteoporosis who had previously completed the 3-yr
      Vertebral Efficacy with Risedronate Therapy MultiNational (VERT-MN) pivotal
      trial, plus a 2-yr extension comparing risedronate or placebo for a total of 5
      yr, followed by 2 yr of open-label risedronate treatment were enrolled in these
      trial extensions. MAIN OUTCOME MEASURES: Evaluations included changes in type I
      collagen cross-linked N-telopeptide (NTX)/creatinine (Cr) and bone mineral
      density (BMD) values, fracture incidence, and adverse events. RESULTS: After 1 yr
      of risedronate discontinuation, NTX/Cr levels increased toward baseline in both
      patient groups vs. the values at the end of yr 7. In both treatment groups, off
      treatment total hip and femoral trochanter BMD values decreased, whereas lumbar
      spine and femoral neck BMD were maintained or slightly increased. The adverse
      event profiles were similar between the two treatment groups during yr 8.
      CONCLUSIONS: One year of discontinuation of risedronate treatment in patients who
      had received 2 or 7 yr of risedronate therapy led to increases in NTX/Cr levels
      toward baseline and decreases in femoral trochanter and total hip BMD.

PMID- 21865361
TI  - Preferential fat deposition in subcutaneous versus visceral depots is associated
      with insulin sensitivity.
AB  - BACKGROUND: Studies on the relationship between regional fat and insulin
      resistance yield mixed results. Our objective was to determine whether regional
      fat distribution, independent of obesity, is associated with insulin resistance.
      DESIGN: Subjects included 115 healthy, overweight/moderately obese adults with
      body mass index (BMI) 25-36.9 kg/m(2) who met predetermined criteria for being
      insulin resistant (IR) or insulin sensitive (IS) based on the modified insulin
      suppression test. Computerized tomography was used to quantify visceral adipose
      tissue (VAT), sc adipose tissue (SAT), and thigh adipose tissue. Fat mass in each
      depot was compared according to IR/IS group, adjusting for BMI and sex. RESULTS:
      Despite nearly identical mean BMI in the IR vs. IS groups, VAT and %VAT were
      significantly higher in the IR group, whereas SAT, %SAT, and thigh sc fat were
      significantly lower. In logistic regression analysis, each sd increase in VAT
      increased the odds of being IR by 80%, whereas each increase in SAT decreased the
      odds by 48%; each increase in thigh fat decreased the odds by 59% and retained
      significance after adjusting for other depots. When grouped by VAT tertile, IS
      vs. IR individuals had significantly more SAT. There was no statistically
      significant interaction between sex and these relationships. CONCLUSION: These
      data demonstrate that after adjustment for BMI and VAT mass, sc abdominal and
      thigh fat are protective for insulin resistance, whereas VAT, after adjustment
      for SAT and BMI, has the opposite effect. Whether causal in nature or a marker of
      underlying pathology, these results clarify that regional distribution of fat
      favoring sc depots is associated with lower risk for insulin resistance.

PMID- 21865360
TI  - MicroRNAs in thyroid cancer.
AB  - CONTEXT: Traditionally, factors predisposing to diseases are either genetic
      ("nature") or environmental, also known as lifestyle-related ("nurture").
      Papillary thyroid cancer is an example of a disease where the respective roles of
      these factors are surprisingly unclear. EVIDENCE ACQUISITION: Original articles
      and reviews summarizing our current understanding of the role of microRNA in
      thyroid tumorigenesis are reviewed and evaluated. CONCLUSION: The genetic
      predisposition to papillary thyroid cancer appears to consist of a variety of
      gene mutations that are mostly either of low penetrance and common or of high
      penetrance but rare. Moreover, they likely interact with each other and with
      environmental factors. The culpable genes may not be of the traditional, protein
      coding type. A limited number of noncoding candidate genes have indeed been
      described, and we propose here that the failure to find mutations in traditional
      protein-coding genes is not coincidental. Instead, a more likely hypothesis is
      that changes in the expression of multiple regulatory RNA genes, e.g. microRNAs,
      may be a major mechanism. Our review of the literature strongly supports this
      notion in that a polymorphism in one microRNAs (miR-146a) predisposes to thyroid
      carcinoma, whereas numerous other microRNAs are involved in signaling (mainly
      PTEN/PI3K/AKT and T3/THRB) that is central to thyroid carcinogenesis.

PMID- 21865362
TI  - Testicular failure and male infertility in the monogenic Mulibrey nanism
      disorder.
AB  - CONTEXT: Few monogenic mutations causing human male infertility have been
      identified to date. OBJECTIVE: We studied pubertal development and fecundity in
      males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. DESIGN,
      SETTING, AND PATIENTS: Twenty-eight male MUL patients of the Finnish national
      cohort aged 8.7 to 50.0 yr (median age, 28.8) at the end of observation were
      followed for 10 yr beginning from 2000-2001. MAIN OUTCOME MEASURES: Clinical
      characteristics, reproductive hormone levels, semen quality, and testicular
      histology were assessed. RESULTS: The external genital phenotype was normal. In
      childhood and prepuberty, serum levels of FSH, LH, testosterone (T), and inhibin
      B were normal. Puberty started spontaneously at a median age of 12.6 yr (range,
      11.1-15.0), and FSH, LH, T, and inhibin B levels increased adequately until
      midpuberty. Thereafter, testicular growth and virilization proceeded slowly.
      Concomitantly, FSH, and to a lesser extent LH, showed a progressive increase to
      hypergonadotropic levels in all patients, whereas inhibin B decreased and T
      leveled off. Testicular size was small (median volume, 8.7 ml; range, 3.5-18.3 ml
      in adults). All semen samples showed severe oligoasthenozoospermia or
      azoospermia. None of the patients had a history of spontaneous fertility, but
      four men had undergone infertility treatment, which in one case was successful.
      All histological MUL samples showed varying degrees of degeneration. CONCLUSIONS:
      All adult MUL males have a unique disorder of testicular function with small
      testes, elevated FSH and LH, and low inhibin B. In MUL, mutations in TRIM37 lead
      to disturbance of sexual maturation, and fertility is severely compromised. Thus,
      TRIM37 is a novel gene causing male infertility.

PMID- 21865363
TI  - Treatment of androgen excess in adolescent girls: ethinylestradiol
      cyproteroneacetate versus low-dose pioglitazone-flutamide-metformin.
AB  - OBJECTIVE: The aim was to perform a first comparison between the effects of a
      classic therapy and those of a novel treatment for androgen excess in adolescent
      girls. DESIGN AND SETTING: We conducted a randomized, open-labeled trial at a
      university hospital. PARTICIPANTS: Thirty-four adolescents with hyperinsulinemic
      androgen excess and without risk of pregnancy participated in the study.
      INTERVENTIONS: Ethinyl estradiol-cyproterone acetate (EE-CA) vs. a low-dose
      combination of pioglitazone, flutamide, and metformin (PioFluMet) was
      administered for 6 months. MAIN OUTCOME MEASURES: We assessed hirsutism and acne
      scores; androgen excess; fasting insulin, lipid profile, C-reactive protein, high
      molecular-weight adiponectin, leptin, follistatin; carotid intima-media
      thickness; body composition (absorptiometry); and abdominal fat partitioning
      (magnetic resonance imaging). RESULTS: EE-CA and PioFluMet attenuated the
      androgen excess comparably but had divergent effects on fasting insulinemia; on
      circulating cholesterol, triglycerides, C-reactive protein, high molecular-weight
      adiponectin, leptin, and follistatin; on carotid intima-media thickness; on lean
      mass; and on abdominal, visceral, and hepatic fat, with all these divergences
      pointing to a healthier condition on low-dose PioFluMet. CONCLUSION: Low-dose
      PioFluMet compared favorably to EE-CA in adolescents with androgen excess and
      without pregnancy risk. The efficacy and safety of low-dose PioFluMet remain to
      be studied over a longer term and in larger cohorts.

PMID- 21865364
TI  - Atropine improves insulin sensitivity in both lean and abdominally obese
      subjects.
AB  - BACKGROUND: Dysregulated autonomic nerve activity may contribute to the
      development of type 2 diabetes. The aim of this study was to assess the effects
      of an anticholinergic agent, atropine, and a cholinergic agent, physostigmine, on
      insulin sensitivity in lean and abdominally obese subjects. SUBJECTS AND METHODS:
      In a single-blinded three-way crossover study, six lean and six abdominally obese
      nondiabetic subjects [three males and three females in each group; age, 43.8 +/-
      14.8 vs. 46.8 +/- 4.8 yr (mean +/- sd); body mass index, 22.6 +/- 1.7 vs. 28.8 +/
      1.3 kg/m(2); and waist circumference, 85 +/- 2 vs. 99 +/- 6 cm, respectively]
      were given iv infusions with atropine (15 MUg/kg bolus, 4 MUg/kg . h infusion),
      physostigmine (0.12 MUg/kg . min) or saline (0.9% NaCl) in a randomized treatment
      order. Infusions were started 30 min before and continued throughout a 120-min
      euglycemic (5.6 mm) hyperinsulinemic (40 mU/m(2) . min) clamp. RESULTS: Insulin
      sensitivity (M-value, i.e. glucose infusion rate divided by lean body mass)
      during the last 60 min of the clamp was higher during infusion with atropine than
      saline (9.2 +/- 1.0 vs. 7.6 +/- 1.0 mg/kg lean body mass . min, mean +/- sem; P =
      0.015) in all subjects. Physostigmine did not differ significantly from saline
      (8.2 +/- 1.0). M-values were significantly higher in lean vs. obese [atropine,
      11.6 +/- 1.4 vs. 7.6 +/- 1.3; physostigmine, 10.8 +/- 1.3 vs. 6.3 +/- 1.3; and
      saline, 9.1 +/- 1.4 vs. 6.4 +/- 1.3, respectively (all P < 0.05)], but the
      incremental effect of atropine vs. saline did not differ consistently between
      groups. CONCLUSION: Insulin sensitivity was higher during a short-term atropine
      infusion compared with saline in both lean and abdominally obese subjects. This
      insulin-sensitizing effect of cholinergic blockade is unexpected, and the
      underlying mechanisms should be further investigated.

PMID- 21865365
TI  - Obstetric outcomes in women with Turner karyotype.
AB  - CONTEXT: Women with Turner syndrome (TS) have high risk of cardiovascular
      complications and hypertensive disorders. Few studies have analyzed obstetric
      outcome in women with TS. OBJECTIVE: This study compared obstetric outcome in
      women with TS karyotype with women in the general population. DESIGN: The Swedish
      Genetic Turner Register was cross-linked with the Swedish Medical Birth Register
      between 1973 and 2007. Obstetric outcome in singletons was compared with a
      reference group of 56,000 women from the general population. Obstetric outcome in
      twins was described separately. RESULTS: A total of 202 singletons and three sets
      of twins were born to 115 women with a TS karyotype that was unknown in 52% at
      time of pregnancy. At first delivery, TS women of singletons were older than
      controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0%
      (P = 0.07). Aortic dissection occurred in one woman. Compared with the general
      population, the gestational age was shorter in children born by TS women (-6.4 d,
      P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd
      scores for weight and length at birth were similar. The cesarean section rate was
      35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in
      birth defects in children of TS women as compared with controls. CONCLUSIONS:
      Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons
      of TS women had shorter gestational age, but similar size at birth, adjusted for
      gestational age and sex. Birth defects did not differ between TS and controls.

PMID- 21865366
TI  - Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double
      blind, crossover trial of liothyronine versus levothyroxine.
AB  - CONTEXT: Levothyroxine (L-T(4)) therapy is based on the assumption that the
      conversion of T(4) into T(3) provides adequate amounts of active hormone at
      target tissues. However, in rodents, L-T(4) alone does not restore a euthyroid
      state in all tissues. Previous combination L-T(4)/liothyronine (L-T(3)) therapy
      trials focused on quality-of-life endpoints, and limited information is available
      on the effects on other measures of thyroid hormone action. OBJECTIVE: Our
      objective was to evaluate the efficacy of thyroid hormone replacement with L-T(4)
      or L-T(3) at doses producing equivalent normalization of TSH. PARTICIPANTS,
      DESIGN, AND SETTING: Fourteen hypothyroid patients participated in this
      randomized, double-blind, crossover intervention at the National Institutes of
      Health Clinical Center. INTERVENTIONS: L-T(3) or L-T(4) were administered thrice
      daily to achieve a target TSH from 0.5-1.5 mU/liter. Volunteers were studied as
      inpatients after 6 wk on a stable dose and at the target TSH. MAIN OUTCOME
      MEASURES: Serum thyroid hormones, lipid parameters, and indices of glucose
      metabolism were evaluated. RESULTS: No difference was observed in TSH between L
      T(3) and L-T(4) treatments. L-T(3) resulted in significant weight loss [L-T(4),
      70.6 +/- 12.5, vs. L-T(3), 68.5 +/- 11.9 kg (P = 0.009)] and in a 10.9 +/- 10.0%
      decrease in total cholesterol (P = 0.002), 13.3 +/- 12.1% decrease in low-density
      lipoprotein-cholesterol (P = 0.002), and an 18.3 +/- 28.6% decrease in
      apolipoprotein B (P = 0.018). No significant differences were observed in high
      density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance,
      or insulin sensitivity. CONCLUSIONS: The substitution of L-T(3) for L-T(4) at
      equivalent doses (relative to the pituitary) reduced body weight and resulted in
      greater thyroid hormone action on the lipid metabolism, without detected
      differences in cardiovascular function or insulin sensitivity.

PMID- 21865367
TI  - Cost-effectiveness of a novel molecular test for cytologically indeterminate
      thyroid nodules.
AB  - CONTEXT: Determining which patients with thyroid nodules require surgery is
      limited by cytologically indeterminate findings. A new approach for preoperative
      molecular classification of cytologically indeterminate thyroid nodules has a
      reported sensitivity of 91% and specificity of 75%; however, its cost
      effectiveness has yet to be assessed. OBJECTIVE: Our objective was to evaluate
      the 5-yr cost-effectiveness of routine use of a molecular test in adult patients
      with indeterminate fine-needle aspiration biopsy results from a societal
      perspective. DESIGN: A 16-state Markov decision model was developed.
      Probabilities, costs, and quality-adjusted life years (QALY) were estimated from
      literature review, U.S. Department of Health and Human Services data, Medicare
      reimbursement schedules, and expert opinion. SETTING AND SUBJECTS: Decision
      analysis of a hypothetical group of adult patients with cytologically
      indeterminate thyroid nodules was conducted. MAIN OUTCOME MEASURES: Incremental
      cost-effectiveness ratio was calculated as incremental cost (measured in U.S.
      dollars) divided by incremental effectiveness (measured in QALY). RESULTS:
      Modifying current practice with use of the molecular test resulted in 74% fewer
      surgeries for benign nodules with no greater number of untreated cancers. Over 5
      yr, mean discounted cost estimates were $12,172 for current practice and $10,719
      with the molecular test. Current practice and molecular test use produced 4.50
      and 4.57 QALY, respectively. CONCLUSIONS: Use of this novel molecular test for
      differential diagnosis of cytologically indeterminate thyroid nodules can
      potentially avoid almost three fourths of currently performed surgeries in
      patients with benign nodules. Compared with current practice based on cytological
      findings alone, use of this test may result in lower overall costs and modestly
      improved quality of life for patients with indeterminate thyroid nodules.

PMID- 21865368
TI  - Clinical review#: Lipodystrophies: genetic and acquired body fat disorders.
AB  - CONTEXT: Lipodystrophies are heterogeneous, genetic or acquired disorders
      characterized by selective loss of body fat and predisposition to insulin
      resistance. The extent of fat loss determines the severity of associated
      metabolic complications such as diabetes mellitus, hypertriglyceridemia, and
      hepatic steatosis. EVIDENCE ACQUISITION AND SYNTHESIS: Both original and review
      articles were found via PubMed search reporting on clinical features and
      management of various types of lipodystrophies and were integrated with the
      author's knowledge of the field. CONCLUSION: The autosomal recessive congenital
      generalized lipodystrophy and autosomal dominant familial partial lipodystrophy
      (FPL) are the two most common types of genetic lipodystrophies. Mutations in
      AGPAT2, BSCL2, CAV1, and PTRF have been reported in congenital generalized
      lipodystrophy and in LMNA, PPARG, AKT2, and PLIN1 in FPL. CIDEC is the disease
      gene for autosomal recessive, FPL and LMNA and ZMPSTE24 for autosomal recessive,
      mandibuloacral dysplasia-associated lipodystrophy. Recently, an autosomal
      recessive autoinflammatory lipodystrophy syndrome was reported to be due to PSMB8
      mutation. Molecular genetic bases of many rare forms of genetic lipodystrophies
      remain to be elucidated. The most prevalent subtype of acquired lipodystrophy
      currently occurs with prolonged duration of protease inhibitor-containing, highly
      active antiretroviral therapy in HIV-infected patients. The acquired generalized
      and partial lipodystrophies are mainly autoimmune in origin and display
      complement abnormalities. Localized lipodystrophies occur due to drug or vaccine
      injections, pressure, panniculitis, and other unknown reasons. The current
      management includes cosmetic surgery and early identification and treatment of
      metabolic and other complications with diet, exercise, hypoglycemic drugs, and
      lipid-lowering agents.

PMID- 21865369
TI  - Adipose tissue dysregulation in patients with metabolic syndrome.
AB  - CONTEXT: The metabolic syndrome (MetS) is associated with increased risk of
      diabetes and cardiovascular disease (CVD). Numerous groups have shown increased
      circulating biomarkers of inflammation in MetS. However, there are scanty data on
      the cellular sources contributing to this low-grade inflammation. OBJECTIVE: The
      aim of this study was to determine the role of sc adipose tissue (SAT) biology in
      nascent MetS without concomitant diabetes or CVD. PATIENTS AND METHODS: Subjects
      with MetS and controls were recruited after informed consent. Fasting blood was
      collected, and SAT was obtained by biopsy. RESULTS: Circulating biomarkers of
      inflammation and insulin resistance, high-sensitivity C-reactive protein (hsCRP),
      IL-6, IL-1beta, leptin, serum amyloid A, and retinol-binding protein-4 (RBP-4)
      concentrations were significantly higher in the MetS subjects than controls,
      whereas adiponectin concentrations were lower. In SAT, leptin, RBP-4, CRP, serum
      amyloid A, plasminogen activator inhibitor-1, IL-1, IL-6, IL-8, and monocyte
      chemotactic protein-1 (MCP-1) levels were significantly higher in MetS than
      controls. These differences except for RBP-4 persisted after adjusting for waist
      circumference. In addition, there were significantly increased numbers of
      macrophages infiltrating the SAT of MetS and increased numbers of crown-like
      structures compared with controls. hsCRP correlated positively with homeostasis
      model assessment and SAT MCP-1 and negatively with adiponectin. Homeostasis model
      assessment correlated positively with plasminogen activator inhibitor-1, RBP-4,
      and SAT MCP-1. CONCLUSIONS: We make the novel observation that SAT of MetS has
      increased macrophage recruitment with cardinal crown-like structure features and
      contributes to the increased cellular inflammation that produces increased levels
      of biomarkers that are correlated with both insulin resistance and low-grade
      inflammation. These aberrations could contribute to the progression of MetS and
      the increased risk for diabetes and CVD.

PMID- 21865371
TI  - Telomere length in neoplastic and nonneoplastic tissues of patients with familial
      and sporadic papillary thyroid cancer.
AB  - INTRODUCTION: Many studies have found an association between altered telomere
      length (TL), both attrition or elongation, and cancer phenotype. Recently, we
      have reported that patients with the familial form of papillary thyroid cancer
      (FPTC) have short telomeres in blood leucocytes. AIM: To evaluate relative TL
      (RTL) at somatic level in neoplastic and nonneoplastic tissues of patients with
      FPTC (n = 30) and sporadic PTC (n = 46). METHODS: RTL was measured by
      quantitative PCR in neoplastic thyroid tissues, in the corresponding nontumor
      thyroid tissues (normal contralateral thyroid), and in other extrathyroidal
      tissues (lymph nodes, muscles, or buccal mucosa). RTL was also measured in
      adenomas and hyperplastic nodules. In a subset of samples, telomerase expression
      was measured by quantitative PCR. RESULTS: Mean +/- SD RTL of FPTC patients was
      short in neoplastic thyroid tissues (0.87 +/- 0.2) with no difference from the
      normal contralateral thyroid tissues (0.85 +/- 0.11) and extrathyroidal tissues
      (0.85 +/- 0.31). On the contrary, in patients with sporadic PTC, the mean +/- SD
      RTL in the neoplastic tissues (1.73 +/- 0.63) was significantly shorter than that
      found in normal contralateral tissues (2.58 +/- 0.89) and extrathyroidal tissues
      (2.5 +/- 0.86). For all tissue samples (cancer, normal thyroid, and nonthyroidal
      tissues) the mean +/- SD RTL of familial cases was shorter (P < 0.0001) than that
      found in tissues from sporadic PTC. RTL of FPTC was also lower (P < 0.0001) than
      that of 23 follicular adenomas (1.6 +/- 0.7) and 24 hyperplastic nodules (2.2 +/-
      0.9). CONCLUSIONS: Our results demonstrate that short telomeres are a consistent
      feature of PTC, which in familial cases, is not restricted to the tumor tissue.
      This finding suggests that FPTC has a distinct, heritable, genetic background.

PMID- 21865370
TI  - Acute decline in serum sclerostin in response to PTH infusion in healthy men.
AB  - CONTEXT: Animal models suggest that the osteoblast-stimulating actions of PTH are
      mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt
      pathway. The immediate physiological changes in serum sclerostin in response to
      PTH infusion have not been reported in human studies. OBJECTIVE: We sought to
      determine the acute physiological effects of PTH infusion on serum sclerostin and
      bone turnover markers in healthy adult men. DESIGN, SETTING, AND PARTICIPANTS:
      Fifty-three healthy adult men underwent an 18-h iv infusion of human PTH(1-34) at
      a dose of 0.55 U/kg . h. OUTCOMES: Serum levels of ionized calcium, sclerostin,
      and markers of bone formation (osteocalcin and amino-terminal propeptide of type
      I procollagen) and bone resorption (C-telopeptide and N-telopeptide) were
      obtained at 0, 6, 12, and 18 h. RESULTS: Serum ionized calcium, C-telopeptide,
      and N-telopeptide increased, and osteocalcin and amino-terminal propeptide of
      type I procollagen fell linearly throughout the PTH infusion (P < 0.001 for all).
      Average +/- sem sclerostin levels declined from 936 +/- 65 to 813 +/- 63 pg/ml at
      6 h (P < 0.001) and remained stably suppressed for the duration of the PTH
      infusion. There were no significant correlations between change in sclerostin and
      change in bone markers. CONCLUSIONS: Serum sclerostin declined in response to
      acute PTH infusion within 6 h in healthy adult men. The early plateau in
      sclerostin suppression may indicate that maximal stimulation of the Wnt pathway
      is achieved quickly after exposure to PTH. Our findings support the hypothesis
      that PTH may mediate its anabolic effects in part via suppression of sclerostin.

PMID- 21865373
TI  - Is elastography actually useful in the presurgical selection of thyroid nodules
      with indeterminate cytology?
AB  - BACKGROUND: Although fine-needle aspiration cytology remains the mainstay of the
      preoperative workup of thyroid nodules, those with follicular proliferation still
      represent a diagnostic challenge. Real-time elastography (RTE) estimates the
      stiffness/elasticity of lesions and is regarded as a promising technique for the
      presurgical selection of thyroid nodules (including those with indeterminate
      cytology). AIM: Our aim was to verify the potential role of RTE in the
      presurgical diagnosis of cancer in a large cohort of consecutive patients with
      follicular thyroid nodules. PATIENTS AND METHODS: One hundred two patients were
      submitted to conventional ultrasonography and RTE evaluation before being
      operated on for thyroid nodule with indeterminate cytology (54% single nodules).
      Tissue stiffness on RTE was scored from 1 (greatest elasticity) to 4 (no
      elasticity). RESULTS: At conventional ultrasonography examination, the nodules
      (median diameter 2.2 cm) were solid (cystic areas < 10%); microcalcifications
      were detected in 56% of them and a hypoechoic pattern in 64%. Elasticity was high
      in eight cases only (score 1-2) although low in 94 (score 3-4). Cancer was
      diagnosed in 36 nodules (35%), being associated with microcalcifications (P <
      0.0001) and inversely related to nodule diameter (P < 0.01). Malignancy was
      detected in 50% of the nodules with RTE score 1-2 and in 34% of those with score
      3-4. Therefore, either the positive (34%) or the negative predictive value (50%)
      was clinically negligible. CONCLUSIONS: The current study does not confirm the
      recently reported usefulness of RTE in presurgical selection of nodules with
      indeterminate cytology and suggest the need for quantitative analytical
      assessment of nodule stiffness to improve RTE efficacy.

PMID- 21865374
TI  - Clinical review: Lessons learned from the hGH era.
AB  - Today, many medical interventions that begin as treatments for disease often
      expand into therapies that reduce disability, lessen disadvantage, or even confer
      advantage. Forces that propel profitable drugs, devices, and procedures dominate
      over considerations of efficient and equitable distribution of resources. This
      dominance is fueled by industry-physician collaborations often biased by prior
      assumptions, reliant on surrogate outcomes, and advantageous to marketing.
      Interventions are justified by "medicalization" of physiologic variations (e.g.
      short stature) as defects or disease, and nudged into "standard practice" by key
      opinion leaders. The story below of recombinant human growth hormone (hGH)
      treatment of short stature is one vivid example, but others (e.g. expansion of
      drug treatment to "optimize" cholesterol profiles, bone health, psychological
      well-being) can be found throughout medicine. In the new obesity era, lessons
      learned from the hGH era will be needed to keep the field of pediatric
      endocrinology empowered to make the key clinical decisions, and free of
      unintended consequences for patients and runaway health care inflation for
      society.

PMID- 21865372
TI  - Serum level of triglycerides is a potent risk factor comparable to LDL
      cholesterol for coronary heart disease in Japanese patients with type 2 diabetes:
      subanalysis of the Japan Diabetes Complications Study (JDCS).
AB  - CONTEXT: Risk factors for cardiovascular complications in Japanese patients with
      diabetes have not been fully elucidated. OBJECTIVE: Our objective was to
      determine incidence of and risk factors for coronary heart disease (CHD) and
      stroke in Japanese diabetic patients. DESIGN AND SETTINGS: We conducted a
      prospective study at 59 hospitals throughout Japan. PATIENTS: Patients included
      940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history
      of cardiovascular complications who were followed for a median of 7.86 yr.
      INTERVENTION: This was an observational study. MAIN OUTCOME MEASURES: Incidence
      of CHD and stroke was evaluated. RESULTS: Incidences of CHD and stroke per 1000
      person-years were 9.59 and 7.45, respectively, whereas those of myocardial and
      brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis
      revealed that the serum log-transformed triglyceride level was a potent and
      independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval
      (CI) = 1.22-1.94 per 1 sd increase), comparable to low-density lipoprotein (LDL)
      cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 sd increase). Triglycerides and
      LDL cholesterol linearly and continuously increased CHD risk, and subjects in the
      top third for both had markedly high risks of CHD, and their effects were
      possibly additive. However, serum triglycerides worked independently of blood
      pressure levels. Systolic blood pressure was the only significant predictor for
      stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 sd increase).
      CONCLUSIONS: In Japanese patients with type 2 diabetes, the serum triglyceride
      level was a leading predictor of CHD, comparable to LDL cholesterol. Because the
      serum triglyceride level is not a leading predictor of CHD in diabetic subjects
      in Western countries, ethnic group-specific strategies for prevention of diabetic
      macroangiopathy may be indicated.

PMID- 21865375
TI  - Long-term results of continuous subcutaneous recombinant PTH (1-34) infusion in
      children with refractory hypoparathyroidism.
AB  - Hypoparathyroidism in children is most often due to mutations in genes involved
      in parathyroid development and calcium homeostasis signaling. Some rare cases
      result from autoimmune attack on the parathyroid glands as a part of the type 1
      polyglandular failure syndrome (autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy). The majority of cases of pediatric hypoparathyroidism are
      well controlled under conventional treatment with calcium and vitamin D analogs.
      However, this treatment may be difficult to manage, especially in two situations:
      1) in the context of autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy and 2) activating mutations in the calcium-sensing receptor. We
      successfully treated three patients with hypoparathyroidism with continuous
      subcutaneous administration of rhPTH(1-34) (recombinant human PTH(1-34)), two of
      which were refractory to conventional therapy.

PMID- 21865376
TI  - Genomic and proteomic characterization of the broad-host-range Salmonella phage
      PVP-SE1: creation of a new phage genus.
AB  - (Bacterio)phage PVP-SE1, isolated from a German wastewater plant, presents a high
      potential value as a biocontrol agent and as a diagnostic tool, even compared to
      the well-studied typing phage Felix 01, due to its broad lytic spectrum against
      different Salmonella strains. Sequence analysis of its genome (145,964 bp) shows
      it to be terminally redundant and circularly permuted. Its G+C content, 45.6
      mol%, is lower than that of its hosts (50 to 54 mol%). We found a total of 244
      open reading frames (ORFs), representing 91.6% of the coding capacity of the
      genome. Approximately 46% of encoded proteins are unique to this phage, and 22.1%
      of the proteins could be functionally assigned. This myovirus encodes a large
      number of tRNAs (n=24), reflecting its lytic capacity and evolution through
      different hosts. Tandem mass spectrometric analysis using electron spray
      ionization revealed 25 structural proteins as part of the mature phage particle.
      The genome sequence was found to share homology with 140 proteins of the
      Escherichia coli bacteriophage rV5. Both phages are unrelated to any other known
      virus, which suggests that an "rV5-like virus" genus should be created within the
      Myoviridae to contain these two phages.

PMID- 21865377
TI  - The HIV/AIDS vaccine candidate MVA-B administered as a single immunogen in humans
      triggers robust, polyfunctional, and selective effector memory T cell responses
      to HIV-1 antigens.
AB  - Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV
      1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we
      describe the nature of T cell immune responses induced in healthy volunteers
      participating in a phase I clinical trial in Spain after intramuscular
      administration of three doses of the recombinant MVA-B-expressing monomeric gp120
      and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of
      the volunteers immunized had a positive specific T cell response at any time
      postvaccination as detected by gamma interferon (IFN-gamma) intracellular
      cytokine staining (ICS) assay. The CD4(+) T cell responses were predominantly Env
      directed, whereas the CD8(+) T cell responses were similarly distributed against
      Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was
      similar to that obtained after the third dose of MVA-B vaccination, and the
      responses were sustained (84.6% at week 48). Vaccine-induced CD8(+) T cells to
      HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the
      effector memory (TEM) and terminally differentiated effector memory (TEMRA) T
      cell populations. Antivector T cell responses were mostly induced by CD8(+) T
      cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate
      that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic,
      inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to
      HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile
      of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine
      candidate.

PMID- 21865378
TI  - trans-Repression of protein expression dependent on the Epstein-Barr virus
      promoter Wp during latency.
AB  - An ordered silencing of Epstein-Barr virus (EBV) latency gene transcription is
      critical for establishment of persistent infection within B lymphocytes, yet the
      mechanisms responsible and the role that the virus itself may play are unclear.
      Here we describe two B-cell superinfection models with which to address these
      problems. In the first, Burkitt lymphoma (BL) cells that maintain latency I, when
      superinfected, initially supported transcription from the common EBNA promoters
      Wp and Cp (latency III) but ultimately transitioned to latency I (Cp/Wp silent),
      an essential requirement for establishment of EBV latency in vivo. We used this
      model to test whether the early lytic-cycle gene BHLF1, implicated in silencing
      of the Cp/Wp locus, is required to establish latency I. Upon superinfection with
      EBV deleted for the BHLF1 locus, however, we have demonstrated that BHLF1 is not
      essential for this aspect of EBV latency. In the second model, BL cells that
      maintain Wp-restricted latency, a variant program in which Cp is silent but Wp
      remains active, sustained the latency III program of transcription from the
      superinfecting-virus genomes, failing to transition to latency I. Importantly,
      there was substantial reduction in Wp-mediated protein expression from endogenous
      EBV genomes, in the absence of Cp reactivation, that could occur independent of a
      parallel decrease in mRNA. Thus, our data provide evidence of a novel,
      potentially posttranscriptional mechanism for trans-repression of Wp-dependent
      gene expression. We suggest that this may ensure against overexpression of the
      EBV nuclear antigens (EBNAs) prior to the transcriptional repression of Wp in cis
      that occurs upon activation of Cp.

PMID- 21865379
TI  - Mutation of glutamine to arginine at position 548 of IE2 86 in human
      cytomegalovirus leads to decreased expression of IE2 40, IE2 60, UL83, and UL84
      and increased transcription of US8-9 and US29-32.
AB  - The IE2 86 protein of human cytomegalovirus (HCMV) is essential for productive
      infection. The mutation of glutamine to arginine at position 548 of IE2 86 causes
      the virus to grow both slowly and to very low titers, making it difficult to
      study this mutant via infection. In this study, Q548R IE2 86 HCMV was produced on
      the complementing cell line 86F/40HA, which allowed faster and higher-titer
      production of mutant virus. The main defects observed in this mutant were greatly
      decreased expression of IE2 40, IE2 60, UL83, and UL84. Genome replication and
      the induction of cell cycle arrest were found to proceed at or near wild-type
      levels, and there was no defect in transitioning to early or late protein
      expression. Q548R IE2 86 was still able to interact with UL84. Furthermore, Q548R
      IE2 40 maintained the ability to enhance UL84 expression in a cotransfection
      assay. Microarray analysis of Q548R IE2 HCMV revealed that the US8, US9, and US29
      32 transcripts were all significantly upregulated. These results further confirm
      the importance of IE2 in UL83 and UL84 expression as well as pointing to several
      previously unknown regions of the HCMV genome that may be regulated by IE2.

PMID- 21865380
TI  - Coreplication of the major genotype group members of porcine circovirus type 2 as
      a prerequisite to coevolution may explain the variable disease manifestations.
AB  - A member of the family Circoviridae, porcine circovirus type 2 (PCV2), is
      associated with postweaning multisystemic wasting syndrome (PMWS), a recent
      emerging disease worldwide. PCV2 is also found in clinically asymptomatic
      animals. This paradoxical finding makes the syndrome etiology challenging. We
      developed new assays to study PCV2 with links to syndrome etiology. For analysis,
      we used PCV2-infected tissues from subclinically infected and diseased piglets.
      We compared antigen- and PCV2 DNA-derived signals for tissue localization and
      intensity. Oligonucleotides were designed to the signature motif of the PCV2
      capsid open reading frame to discriminate experimentally between PCV2 genotype
      groups by PCR, in situ hybridization (ISH), and fluorescence in situ
      hybridization (FISH). Unexpectedly, all PCV2-infected animals carried both PCV2a
      and PCV2b genotype group members. Using confocal microscopy, genotype single-cell
      infections and cell superinfections were visible. Additionally, we discriminated
      replicative DNA from total PCV2 DNA isoforms with FISH. This aided in our inquiry
      into cellular genotype-specific replication. Importantly, single-genotype-group
      replication was not observed. In infected cells with replicating virus, both
      genotype groups were equally present. These findings suggest PCV2 genotype group
      members relaxed replication regulation requirements and may even point to PCV2
      replication cooperativity in vivo. These observations explain the readily seen
      PCV2 DNA recombinations and the high overall PCV2 genome plasticity. Hence, we
      suggest a novel mechanism of syndrome etiology that consists of a continuously
      changing PCV2 genome pool in hosts and pig herds, posing a constant challenge to
      the individual maturing immune system.

PMID- 21865381
TI  - Improved knockout methodology reveals that frog virus 3 mutants lacking either
      the 18K immediate-early gene or the truncated vIF-2alpha gene are defective for
      replication and growth in vivo.
AB  - To better assess the roles of frog virus 3 (FV3; genus Ranavirus, family
      Iridoviridae) genes in virulence and immune evasion, we have developed a reliable
      and efficient method to systematically knock out (KO) putative virulence genes by
      site-specific integration into the FV3 genome. Our approach utilizes a dual
      selection marker consisting of the puromycin resistance gene fused in frame with
      the enhanced green fluorescent protein (EGFP) reporter (Puro-EGFP cassette) under
      the control of the FV3 immediate-early (IE) 18K promoter. By successive rounds of
      selection for puromycin resistance and GFP expression, we have successfully
      constructed three recombinant viruses. In one, a "knock-in" mutant was created by
      inserting the Puro-EGFP cassette into a noncoding region of the FV3 genome (FV3
      Puro/GFP). In the remaining two, KO mutants were constructed by replacement of
      the truncated viral homolog of eIF-2alpha (FV3-DeltavIF-2alpha) or the 18K IE
      gene (FV3-Delta18K) with the Puro-EGFP cassette. The specificity of recombination
      and the clonality of each mutant were confirmed by PCR, sequencing, and
      immunofluorescence microscopy. Viral replication of each recombinant in cell
      culture was similar to that of parental FV3; however, infection in Xenopus laevis
      tadpoles revealed that FV3-DeltavIF-2alpha and FV3-Delta18K replicated less and
      resulted in lower mortality than did GFP-FV3 and wild-type FV3. Our results
      suggest that 18K, which is conserved in all ranaviruses, and the truncated vIF
      2alpha gene contribute to virulence. In addition, our study describes a powerful
      methodology that lays the foundation for the discovery of potentially new
      ranaviral genes involved in virulence and immune escape.

PMID- 21865382
TI  - Inhibition of dengue virus by targeting viral NS4B protein.
AB  - We report a novel inhibitor that selectively suppresses dengue virus (DENV) by
      targeting viral NS4B protein. The inhibitor was identified by screening a 1.8
      million-compound library using a luciferase replicon of DENV serotype 2 (DENV-2).
      The compound specifically inhibits all four serotypes of DENV (50% effective
      concentration [EC(50)], 1 to 4 MUM; and 50% cytotoxic concentration [CC(50)], >40
      MUM), but it does not inhibit closely related flaviviruses (West Nile virus and
      yellow fever virus) or nonflaviviruses (Western equine encephalomyelitis virus,
      Chikungunya virus, and vesicular stomatitis virus). A mode-of-action study
      suggested that the compound inhibits viral RNA synthesis. Replicons resistant to
      the inhibitor were selected in cell culture. Sequencing of the resistant
      replicons revealed two mutations (P104L and A119T) in the viral NS4B protein.
      Genetic analysis, using DENV-2 replicon and recombinant viruses, demonstrated
      that each of the two NS4B mutations alone confers partial resistance and double
      mutations confer additive resistance to the inhibitor in mammalian cells. In
      addition, we found that a replication defect caused by a lethal NS4B mutation
      could be partially rescued through trans complementation. The ability to
      complement NS4B in trans affected drug sensitivity when a single cell was
      coinfected with drug-sensitive and drug-resistant viruses. Mechanistically, NS4B
      was previously shown to interact with the viral NS3 helicase domain; one of the
      two NS4B mutations recovered in our resistance analysis-P104L-abolished the NS3
      NS4B interaction (I. Umareddy, A. Chao, A. Sampath, F. Gu, and S. G. Vasudevan,
      J. Gen. Virol. 87:2605-2614, 2006). Collectively, the results suggest that the
      identified inhibitor targets the DENV NS4B protein, leading to a defect in viral
      RNA synthesis.

PMID- 21865383
TI  - A duck enteritis virus-vectored bivalent live vaccine provides fast and complete
      protection against H5N1 avian influenza virus infection in ducks.
AB  - Ducks play an important role in the maintenance of highly pathogenic H5N1 avian
      influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks
      has important implications for the eradication of the disease in poultry and its
      prevention in humans. The inactivated influenza vaccine is expensive, labor
      intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks.
      Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used
      routinely to control lethal DEV infections in many duck-producing areas. Here, we
      first established a system to generate the DEV vaccine strain by using the
      transfection of overlapping fosmid DNAs. Using this system, we constructed two
      recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA)
      gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained
      within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck
      studies indicated that rDEV-us78HA had protective efficacy similar to that of the
      live DEV vaccine against lethal DEV challenge; importantly, a single dose of
      10(6) PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus
      challenge in as little as 3 days postvaccination. The protective efficacy against
      both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks
      was slightly weaker than that provided by rDEV-us78HA. These results demonstrate,
      for the first time, that recombinant DEV is suitable for use as a bivalent live
      attenuated vaccine, providing rapid protection against both DEV and H5N1 virus
      infection in ducks.

PMID- 21865384
TI  - Systems analysis of immune responses in Marek's disease virus-infected chickens
      identifies a gene involved in susceptibility and highlights a possible novel
      pathogenicity mechanism.
AB  - Marek's disease virus (MDV) is a highly contagious oncogenic alphaherpesvirus
      that causes disease that is both a cancer model and a continuing threat to the
      world's poultry industry. This comprehensive gene expression study analyzes the
      host response to infection in both resistant and susceptible lines of chickens
      and inherent expression differences between the two lines following the infection
      of the host. A novel pathogenicity mechanism, involving the downregulation of
      genes containing HIC1 transcription factor binding sites as early as 4 days
      postinfection, was suggested from this analysis. HIC1 drives antitumor
      mechanisms, suggesting that MDV infection switches off genes involved in
      antitumor regulation several days before the expression of the MDV oncogene meq.
      The comparison of the gene expression data to previous QTL data identified
      several genes as candidates for involvement in resistance to MD. One of these
      genes, IRG1, was confirmed by single nucleotide polymorphism analysis to be
      involved in susceptibility. Its precise mechanism remains to be elucidated,
      although the analysis of gene expression data suggests it has a role in
      apoptosis. Understanding which genes are involved in susceptibility/resistance to
      MD and defining the pathological mechanisms of the disease gives us a much
      greater ability to try to reduce the incidence of this virus, which is costly to
      the poultry industry in terms of both animal welfare and economics.

PMID- 21865386
TI  - Matrix protein-specific IgA antibody inhibits measles virus replication by
      intracellular neutralization.
AB  - Measles virus (MV) is still an imposing threat to public health. The matrix (M)
      protein has been shown not only to function as a structure block in the assembled
      MV virions, but also to regulate viral RNA synthesis, playing an important role
      in MV's replication and assembly. In the present study, we generated a panel of
      IgG monoclonal antibodies (MAbs) against M protein and successfully obtained one
      IgA MAb (5H7) from the IgG panel. Employing the polarized Vero cells grown in the
      two-chamber transwell model, we investigated whether M-specific 5H7 IgA MAb could
      suppress MV's replication and assembly. The data presented indicate that, while
      failing to show the activities of traditional neutralization and immune
      exclusion, M-specific IgA MAb was able to effectively inhibit viral replication
      by intracellular neutralization (78%), supporting the notion that the M protein
      is important for MV assembly and replication and implying that the M protein was
      an effective target antigen. The data also showed that MV had a long entry and
      assembly phase during viral replication, providing an extended window for IgA
      intervention. The colocalization of M proteins and M-specific 5H7 IgA MAbs
      demonstrated that the intracellular neutralization was due to the direct binding
      of the M-specific 5H7 IgA MAbs to the M proteins. In summary, the present study
      has added another example showing that IgA antibodies targeting internal viral
      antigens could proactively participate in mucosal immune protection by
      intracellular neutralization and has provided evidence that M protein might be
      included as a target antigen in future MV vaccine design.

PMID- 21865385
TI  - Alphavirus-induced encephalomyelitis: antibody-secreting cells and viral
      clearance from the nervous system.
AB  - Sindbis virus (SINV) infection of the central nervous system (CNS) provides a
      model for understanding the role of the immune response in recovery from
      alphavirus infection of neurons. Virus clearance occurred in three phases:
      clearance of infectious virus (days 3 to 7), clearance of viral RNA (days 8 to
      60), and maintenance of low levels of viral RNA (>day 60). The antiviral immune
      response was initiated in the cervical lymph nodes with rapid extrafollicular
      production of plasmablasts secreting IgM, followed by germinal center production
      of IgG-secreting and memory B cells. The earliest inflammatory cells to enter the
      brain were CD8(+) T cells, followed by CD4(+) T cells and CD19(+) B cells. During
      the clearance of infectious virus, effector lymphocytes in the CNS were primarily
      CD8(+) T cells and IgM antibody-secreting cells (ASCs). During the clearance of
      viral RNA, there were more CD4(+) than CD8(+) T cells, and B cells included IgG
      and IgA ASCs. At late times after infection, ASCs in the CNS were primarily
      CD19(+) CD38(+) CD138(-) Blimp-1(+) plasmablasts, with few fully differentiated
      CD38(-) CD138(+) Blimp-1(+) plasma cells. CD19(+) CD38(+) surface Ig(+) memory B
      cells were also present. The level of antibody to SINV increased in the brain
      over time, and the proportion of SINV-specific ASCs increased from 15% of total
      ASCs at day 14 to 90% at 4 to 6 months, suggesting specific retention in the CNS
      during viral RNA persistence. B cells in the CNS continued to differentiate, as
      evidenced by accumulation of IgA ASCs not present in peripheral lymphoid tissue
      and downregulation of major histocompatibility complex (MHC) class II expression
      on plasmablasts. However, there was no evidence of germinal center activity or
      IgG avidity maturation within the CNS.

PMID- 21865387
TI  - Naturally occurring antibodies in humans can neutralize a variety of influenza
      virus strains, including H3, H1, H2, and H5.
AB  - Influenza A viruses are classified into 16 subtypes according to the serotypes of
      hemagglutinin (HA). It is generally thought that neutralizing antibodies (Abs)
      are not broadly cross-reactive among HA subtypes. We examined the repertoire of
      neutralizing Abs against influenza viruses in humans. B lymphocytes were
      collected from donors by apheresis, and Ab libraries were constructed by using
      phage-display technology. Anti-HA clones were isolated by screening with H3N2
      viruses. Their binding activity was examined, and four kinds of Abs showing broad
      strain specificity were identified from one donor. Two of the Abs, F045-092 and
      F026-427, were extensively analyzed. They neutralized not only H3N2 but also
      H1N1, H2N2, and H5N1 viruses, although the activities were largely varied. Flow
      cytometry suggested that they have the ability to bind to HA and HA1 artificially
      expressed on the cell surface. They show hemagglutination inhibition activity and
      do not compete with C179, an Ab thought to bind to the stalk region. F045-092
      competes with Abs that recognize sites A and B for binding to HA. Furthermore,
      the serine at residue 136 in site A could be a part of the epitope. Thus, it is
      likely that F045-092 and F026-427 bind to a conserved epitope in the head region
      formed by HA1. Interestingly, while the V(H)1-69 gene can encode MAbs against the
      HA stem that are group 1 specific, F045-092 and its relatives that recognize the
      head region also use V(H)1-69. The possible epitope recognized by these clones is
      discussed.

PMID- 21865389
TI  - MyD88 plays an essential role in inducing B cells capable of differentiating into
      antibody-secreting cells after vaccination.
AB  - We investigated the roles of MyD88, an innate adaptor signaling molecule, in
      inducing protective humoral immunity after vaccination with influenza virus-like
      particles (VLPs). MyD88 knockout C57BL/6 mice (MyD88(-/-) mice) vaccinated with
      influenza VLPs showed significant defects in inducing IgG2a/c isotype antibodies
      and in generating splenic recall memory B cell responses and antibody-secreting
      plasma cells in the bone marrow. The protective efficacy of influenza VLP
      vaccination was lower in MyD88(-/-) mice than in the wild-type mice. Our findings
      indicate that MyD88-mediated innate signaling pathways are important for
      effectively inducing primary and boost immune responses, T helper type 1 isotype
      switched antibodies, and gamma interferon (IFN-gamma)-secreting T cell responses.
      In particular, the results in this study demonstrated for the first time that
      MyD88-mediated immune activation is likely an essential pathway for effective
      generation of long-lived antibody-secreting plasma cells and highly protective
      immunity after vaccination with influenza VLPs. This study provides insight into
      mechanisms by which recombinant viral vaccines induce protective immunity via the
      MyD88-mediated innate immune signaling pathway.

PMID- 21865388
TI  - Determinants of bluetongue virus virulence in murine models of disease.
AB  - Bluetongue is a major infectious disease of ruminants that is caused by
      bluetongue virus (BTV). In this study, we analyzed virulence and genetic
      differences of (i) three BTV field strains from Italy maintained at either a low
      (L strains) or high (H strains) passage number in cell culture and (ii) three
      South African "reference" wild-type strains and their corresponding live
      attenuated vaccine strains. The Italian BTV L strains, in general, were lethal
      for both newborn NIH-Swiss mice inoculated intracerebrally and adult type I
      interferon receptor-deficient (IFNAR(-/-)) mice, while the virulence of the H
      strains was attenuated significantly in both experimental models. Similarly, the
      South African vaccine strains were not pathogenic for IFNAR(-/-) mice, while the
      corresponding wild-type strains were virulent. Thus, attenuation of the virulence
      of the BTV strains used in this study is not mediated by the presence of an
      intact interferon system. No clear distinction in virulence was observed for the
      South African BTV strains in newborn NIH-Swiss mice. Full genomic sequencing
      revealed relatively few amino acid substitutions, scattered in several different
      viral proteins, for the strains found to be attenuated in mice compared to the
      pathogenic related strains. However, only the genome segments encoding VP1, VP2,
      and NS2 consistently showed nonsynonymous changes between all virulent and
      attenuated strain pairs. This study established an experimental platform for
      investigating the determinants of BTV virulence. Future studies using reverse
      genetics will allow researchers to precisely map and "weight" the relative
      influences of the various genome segments and viral proteins on BTV virulence.

PMID- 21865390
TI  - Inhibition of hepatitis B virus replication by cIAP2 involves accelerating the
      ubiquitin-proteasome-mediated destruction of polymerase.
AB  - Cellular inhibitor of apoptosis protein 2 (cIAP2) is a potent suppressor of
      apoptotic cell death. We have shown previously that cIAP2 is involved in the
      tumor necrosis factor alpha (TNF-alpha)-induced anti-hepatitis B virus (HBV)
      response; however, the mechanism for this antiviral effect remains unclear. In
      the present study, we demonstrate that cIAP2 can significantly reduce the levels
      of HBV DNA replication intermediates but not the total viral RNA or core protein
      levels. Domain-mapping analysis revealed that the carboxy-terminal domains of
      cIAP2 were indispensable for this anti-HBV ability and that an E3 ligase
      deficient mutant of cIAP2 (termed cIAP2*) completely lost its antiviral activity.
      We further identified HBV polymerase as the target of cIAP2. Overexpression of
      cIAP2 but not cIAP2* reduced polymerase protein levels, while cIAP2 knockdown
      increased polymerase expression. In addition, we observed that cIAP2 promoted the
      degradation of the viral polymerase through a proteasome-dependent pathway.
      Further experiments demonstrated that cIAP2 can bind to polymerase and promote
      its polyubiquitylation. Finally, we found that cIAP2 downregulated the
      encapsidation of HBV pregenomic RNA. Taken together, these data reveal a novel
      mechanism for the inhibition of HBV replication by cIAP2 via acceleration of the
      ubiquitin-proteasome-mediated decay of polymerase and reduction of the
      encapsidation of HBV pregenomic RNA, making this mechanism a novel strategy for
      HBV therapy.

PMID- 21865391
TI  - Heterogeneous nuclear ribonucleoprotein A2 participates in the replication of
      Japanese encephalitis virus through an interaction with viral proteins and RNA.
AB  - Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is kept in
      a zoonotic transmission cycle between pigs and mosquitoes. JEV causes infection
      of the central nervous system with a high mortality rate in dead-end hosts,
      including humans. Many studies have suggested that the flavivirus core protein is
      not only a component of nucleocapsids but also an important pathogenic
      determinant. In this study, we identified heterogeneous nuclear ribonucleoprotein
      A2 (hnRNP A2) as a binding partner of the JEV core protein by pulldown
      purification and mass spectrometry. Reciprocal coimmunoprecipitation analyses in
      transfected and infected cells confirmed a specific interaction between the JEV
      core protein and hnRNP A2. Expression of the JEV core protein induced cytoplasmic
      retention of hnRNP A2 in JEV subgenomic replicon cells. Small interfering RNA
      (siRNA)-mediated knockdown of hnRNP A2 resulted in a 90% reduction of viral RNA
      replication in cells infected with JEV, and the reduction was cancelled by the
      expression of an siRNA-resistant hnRNP A2 mutant. In addition to the core
      protein, hnRNP A2 also associated with JEV nonstructural protein 5, which has
      both methyltransferase and RNA-dependent RNA polymerase activities, and with the
      5'-untranslated region of the negative-sense JEV RNA. During one-step growth,
      synthesis of both positive- and negative-strand JEV RNAs was delayed by the
      knockdown of hnRNP A2. These results suggest that hnRNP A2 plays an important
      role in the replication of JEV RNA through the interaction with viral proteins
      and RNA.

PMID- 21865392
TI  - The cryo-electron microscopy structure of feline calicivirus bound to junctional
      adhesion molecule A at 9-angstrom resolution reveals receptor-induced flexibility
      and two distinct conformational changes in the capsid protein VP1.
AB  - Caliciviridae are small icosahedral positive-sense RNA-containing viruses and
      include the human noroviruses, a leading cause of infectious acute
      gastroenteritis and feline calicivirus (FCV), which causes respiratory illness
      and stomatitis in cats. FCV attachment and entry is mediated by feline junctional
      adhesion molecule A (fJAM-A), which binds to the outer face of the capsomere,
      inducing a conformational change in the capsid that may be important for viral
      uncoating. Here we present the results of our structural investigation of the
      virus-receptor interaction and ensuing conformational changes. Cryo-electron
      microscopy and three-dimensional image reconstruction were used to solve the
      structure of the virus decorated with a soluble fragment of the receptor at
      subnanometer resolution. In initial reconstructions, the P domains of the capsid
      protein VP1 and fJAM-A were poorly resolved. Sorting experiments led to improved
      reconstructions of the FCV-fJAM-A complex both before and after the induced
      conformational change, as well as in three transition states. These data showed
      that the P domain becomes flexible following fJAM-A binding, leading to a loss of
      icosahedral symmetry. Furthermore, two distinct conformational changes were seen;
      an anticlockwise rotation of up to 15 degrees  of the P domain was observed in
      the AB dimers, while tilting of the P domain away from the icosahedral 2-fold
      axis was seen in the CC dimers. A list of putative contact residues was
      calculated by fitting high-resolution coordinates for fJAM-A and VP1 to the
      reconstructed density maps, highlighting regions in both virus and receptor
      important for virus attachment and entry.

PMID- 21865393
TI  - Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in
      human papillomavirus type 16 E6/E7-expressing keratinocytes.
AB  - A number of epigenetic alterations occur in both the virus and host cellular
      genomes during human papillomavirus (HPV)-associated carcinogenesis, and
      investigations of such alterations, including changes in chromatin proteins and
      histone modifications, have the potential to lead to therapeutic epigenetic
      reversion. We report here that transformed HPV16 E6/E7-expressing primary human
      foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of
      the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not
      exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to
      normal keratinocytes. In contrast, these cells show a reduction in global
      H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We
      further show for the first time that transformation with the HPV16 E6 and E7
      oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2
      Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1
      in these cells. High-grade squamous cervical intraepithelial lesions also showed
      a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating
      with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-,
      KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed
      reduction in H3K27me3 may be due to a combination of reduced activities/levels of
      specific polycomb proteins and increases in demethylases. The dysregulation of
      multiple chromatin proteins resulting in the loss of global H3K27me3 and the
      transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an
      epigenetic signature associated with risk and/or progression of HPV16-associated
      cancers, as well as the potential for epigenetic reversion in the future.

PMID- 21865394
TI  - Fatal outcome of pandemic H1N1 2009 influenza virus infection is associated with
      immunopathology and impaired lung repair, not enhanced viral burden, in pregnant
      mice.
AB  - Pandemic A (H1N1) 2009 influenza virus (pH1N1) infection in pregnant women can be
      severe. The mechanisms that affect infection outcome in this population are not
      well understood. To address this, pregnant and nonpregnant BALB/c mice were
      inoculated with the wild-type pH1N1 strain A/California/04/09. To determine
      whether innate immune responses are associated with severe infection, we measured
      the innate cells trafficking into the lungs of pregnant versus nonpregnant
      animals. Increased infiltration of pulmonary neutrophils and macrophages strongly
      correlated with an elevated mortality in pregnant mice. In agreement with this,
      the product of nitric oxide (nitrite) and several cytokines associated with
      recruitment and/or function of these cells were increased in the lungs of
      pregnant animals. Surprisingly, increased mortality in pregnant mice was not
      associated with higher virus load because equivalent virus titers and
      immunohistochemical staining were observed in the nasal cavities or lungs of all
      mice. To determine whether exacerbated inflammatory responses and elevated
      cellularity resulted in lung injury, epithelial regeneration was measured. The
      lungs of pregnant mice exhibited reduced epithelial regeneration, suggesting
      impaired lung repair. Despite these immunologic alterations, pregnant animals
      demonstrated equivalent percentages of pulmonary influenza virus-specific CD8(+)
      T lymphocytes, although they displayed elevated levels of T-regulator lymphocytes
      (Tregs) in the lung. Also, pregnant mice mounted equal antibody titers in
      response to virus or immunization with a monovalent inactivated pH1N1
      A/California/07/09 vaccine. Therefore, immunopathology likely caused by elevated
      cellular recruitment is an implicated mechanism of severe pH1N1 infection in
      pregnant mice.

PMID- 21865395
TI  - Gypsy and the birth of the SCAN domain.
AB  - SCAN is a protein domain frequently found at the N termini of proteins encoded by
      mammalian tandem zinc finger (ZF) genes, whose structure is known to be similar
      to that of retroviral gag capsid domains and whose multimerization has been
      proposed as a model for retroviral assembly. We report that the SCAN domain is
      derived from the C-terminal portion of the gag capsid (CA) protein from the Gmr1
      like family of Gypsy/Ty3-like retrotransposons. On the basis of sequence
      alignments and phylogenetic distributions, we show that the ancestral host SCAN
      domain (ESCAN for extended SCAN) was exapted from a full-length CA gene from a
      Gmr1-like retrotransposon at or near the root of the tetrapod animal branch. A
      truncated variant of ESCAN that corresponds to the annotated SCAN domain arose
      shortly thereafter and appears to be the only form extant in mammals. The Anolis
      lizard has a large number of tandem ZF genes with N-terminal ESCAN or SCAN
      domains. We predict DNA binding sites for all Anolis ESCAN-ZF and SCAN-ZF
      proteins and demonstrate several highly significant matches to Anolis Gmr1-like
      sequences, suggesting that at least some of these proteins target retroelements.
      SCAN is known to mediate protein dimerization, and the CA protein multimerizes to
      form the core retroviral and retrotransposon capsid structure. We speculate that
      the SCAN domain originally functioned to target host ZF proteins to retroelement
      capsids.

PMID- 21865396
TI  - H5N1 virus-like particle vaccine elicits cross-reactive neutralizing antibodies
      that preferentially bind to the oligomeric form of influenza virus hemagglutinin
      in humans.
AB  - Transmission of pathogenic avian influenza viruses (AIV) from wild birds to
      domestic poultry and humans is continuing in multiple countries around the world.
      In preparation for a potential AIV pandemic, multiple vaccine candidates are
      under development. In the case of H5N1 AIV, a clear shift in transmission from
      clade 1 to clade 2 viruses occurred in recent years. The virus-like particle
      (VLP) represents an economical approach to pandemic vaccine development. In the
      current study, we evaluated the humoral immune response in humans vaccinated with
      H5N1 A/Indonesia/05/2005 (clade 2.1) VLP vaccine manufactured in Sf9 insect
      cells. The VLPs were comprised of the influenza virus hemagglutinin (HA),
      neuraminidase (NA), and matrix 1 (M1) proteins. In an FDA-approved phase I/II
      human clinical study, two doses of H5N1 VLPs at 15, 45, or 90 MUg HA/dose
      resulted in seroconversion and production of functional antibodies. Moreover,
      cross-reactivity against other clade 2 subtypes was demonstrated using virus
      neutralization assays. H5N1 whole-genome fragment phage display libraries (GFPDL)
      were used to elucidate the antibody epitope repertoire in postvaccination human
      sera. Diverse epitopes in HA1/HA2 and NA were recognized by postvaccination sera
      from the two high-dose groups, including large segments spanning the HA1 receptor
      binding domain. Importantly, the vaccine elicited sera that preferentially bound
      to an oligomeric form of recombinant HA1 compared with monomeric HA1. The
      oligomeric/monomeric HA1 binding ratios of the sera correlated with the virus
      neutralizing titers. Additionally, the two high-dose VLP vaccine groups generated
      NA-inhibiting antibodies that were associated with binding to a C-terminal
      epitope close to the sialic acid binding site. These findings represent the first
      report describing the quality of the antibody responses in humans following AIV
      VLP immunization and support further development of such vaccines against
      emerging influenza virus strains.

PMID- 21865397
TI  - Dynamic antibody specificities and virion concentrations in circulating immune
      complexes in acute to chronic HIV-1 infection.
AB  - Understanding the interactions between human immunodeficiency virus type 1 (HIV
      1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is
      critical for defining antibody antiviral capabilities. Antibodies that bind
      virions may prevent transmission by neutralization of virus or mechanically
      prevent HIV-1 migration through mucosal layers. In this study, we quantified
      circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of
      AHI subjects, and compared the levels and antibody specificity to those in
      chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes)
      were in significantly lower levels relative to the viral load in acute infection
      than in chronic HIV-1 infection. The specificities of the antibodies in the
      immune complexes differed between acute and chronic infection (anti-gp41 Ab in
      acute infection and anti-gp120 in chronic infection), potentially suggesting
      different roles in immunopathogenesis for complexes arising at different stages
      of infection. We also determined the ability of circulating IgG from AHI to bind
      infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41
      monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound
      both infectious and noninfectious virions. This was in contrast to the
      neutralizing antibody 2G12 MAb that bound predominantly infectious virions.
      Moreover, the initial antibody response captured acute HIV-1 virions without
      selection for different HIV-1 envelope sequences. In total, this study
      demonstrates that the composition of immune complexes are dynamic over the course
      of HIV-1 infection and are comprised initially of antibodies that nonselectively
      opsonize both infectious and noninfectious virions, likely contributing to the
      lack of efficacy of the antibody response during acute infection.

PMID- 21865398
TI  - Host regulatory network response to infection with highly pathogenic H5N1 avian
      influenza virus.
AB  - During the last decade, more than half of humans infected with highly pathogenic
      avian influenza (HPAI) H5N1 viruses have died, yet virus-induced host signaling
      has yet to be clearly elucidated. Airway epithelia are known to produce
      inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a
      comprehensive analysis of the host response in this cell type is lacking. Here,
      we leveraged a system approach to identify and statistically validate signaling
      subnetworks that define the dynamic transcriptional response of human bronchial
      epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1,
      VN1203). Importantly, we validated a subset of transcripts from one subnetwork in
      both Calu-3 cells and mice. A more detailed examination of two subnetworks
      involved in the immune response and keratinization processes revealed potential
      novel mediators of HPAI H5N1 pathogenesis and host response signaling. Finally,
      we show how these results compare to those for a less virulent strain of
      influenza virus. Using emergent network properties, we provide fresh insight into
      the host response to HPAI H5N1 virus infection and identify novel avenues for
      perturbation studies and potential therapeutic interventions for fatal HPAI H5N1
      disease.

PMID- 21865400
TI  - A phase II trial of single-agent bevacizumab in patients with recurrent
      anaplastic glioma.
AB  - The purpose of this study was to evaluate the activity of single-agent
      bevacizumab in patients with recurrent anaplastic glioma and assess correlative
      advanced imaging parameters. Patients with recurrent anaplastic glioma were
      treated with bevacizumab 10 mg/kg every 2 weeks. Complete patient evaluations
      were repeated every 4 weeks. Correlative dynamic contrast-enhanced MR and
      (18)fluorodeoxyglucose PET imaging studies were obtained to evaluate physiologic
      changes in tumor and tumor vasculature at time points including baseline, 96 h
      after the first dose, and after the first 4 weeks of therapy. Median overall
      survival was 12 months (95% confidence interval [CI]: 6.08-22.8). Median
      progression-free survival was 2.93 months (95% CI: 2.01-4.93), and 6-month
      progression-free survival was 20.9% (95% CI: 10.3%-42.5%). Thirteen (43%)
      patients achieved a partial response. The most common grade >= 3 treatment
      related toxicities were hypertension, hypophosphatemia, and thromboembolism.
      Single-agent bevacizumab produces significant radiographic response in patients
      with recurrent anaplastic glioma but did not meet the 6-month progression-free
      survival endpoint. Early change in enhancing tumor volume at 4 days after start
      of therapy was the most significant prognostic factor for overall and progression
      free survival.

PMID- 21865399
TI  - "Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non
      small cell lung cancer.
AB  - Erlotinib is effective for epidermal growth factor receptor (EGFR) mutant lung
      cancer, but CNS penetration at standard daily dosing is limited. We previously
      reported that intermittent "pulsatile" administration of high-dose (1500 mg)
      erlotinib once weekly was tolerable and achieved concentrations in cerebrospinal
      fluid exceeding the half maximal inhibitory concentration for EGFR mutant lung
      cancer cells in a patient with leptomeningeal metastases; we now expand this
      paradigm to a series of 9 patients. We retrospectively identified patients with
      EGFR mutant lung cancer treated with pulsatile erlotinib for CNS metastases
      (brain and/or leptomeningeal) that occurred despite conventional daily erlotinib
      or other EGFR tyrosine kinase inhibitors. Mutations in available lung and CNS
      tissue were correlated with efficacy. Erlotinib was administered as monotherapy
      at a median dose of 1500 mg weekly. Best CNS radiographic response was partial in
      67% (6/9, including 2 with isolated leptomeningeal metastases), stable disease in
      11% (1/9), and progressive disease in 22% (2/9). Median time to CNS progression
      was 2.7 months (range, 0.8-14.5 months) and median overall survival was 12 months
      (range, 2.5 months-not reached). Treatment was well tolerated. No acquired
      resistance mutations in EGFR were identified in the CNS metastases of 4 patients,
      including 1 harboring T790M outside the CNS. Pulsatile erlotinib can control CNS
      metastases from EGFR mutant lung cancer after failure of standard daily dosing.
      CNS disease may not harbor acquired resistance mutations that develop
      systemically. A prospective trial is planned.

PMID- 21865401
TI  - MRI apparent diffusion coefficient reflects histopathologic subtype, axonal
      disruption, and tumor fraction in diffuse-type grade II gliomas.
AB  - The apparent diffusion coefficient (ADC) determined from MR diffusion tensor
      imaging (DTI) has shown promise for distinguishing World Health Organization
      grade II astrocytoma (AS) from the more prognostically favorable grade II
      oligodendroglioma (OD). Since mixed oligoastrocytomas (OAs) with codeletions in
      chromosomes 1p and 19q confer prognoses similar to those of OD, we questioned
      whether a previously determined ADC-based criterion for distinguishing OD and AS
      would hold on an independent set of gliomas that included OA with codeleted or
      intact 1p/19q chromosomes. We also questioned whether the ADC is associated with
      the tumor microstructure. ADC colormaps generated from presurgical DTI scans were
      used to guide the collection of biopsies from each tumor. The median normalized
      ADC distinguished OD from AS with 91% sensitivity and 92% specificity. 1p/19q
      codeleted OAs were always classified as ODs, while 1p/19q intact OAs were always
      classified as ASs. There were positive associations between the ADC and both the
      SMI-31 score of axonal disruption and the fraction of tumor cells in the
      biopsies. The ADC of OD and 1p/19q codeleted OA was more associated with tumor
      fraction, while the ADC of AS and 1p/19q intact OA was more associated with SMI
      31 score. We conclude that our previously determined threshold median ADC can
      distinguish grade II OD and AS on a new patient cohort and that the distinctions
      extend to OA with codeleted and intact 1p/19q chromosomes. Further, the ADC in
      grade II gliomas is associated with the fraction of tumor cells and degree of
      axonal disruption in tumor subregions.

PMID- 21865402
TI  - Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial
      tight junction defects in coeliac disease.
AB  - BACKGROUND: Epithelial barrier defects are well known in coeliac disease, but the
      mechanisms are only poorly defined. It is unclear, whether barrier disturbance
      reflects upregulated epithelial transcytosis or paracellular leakage. OBJECTIVE:
      To characterise the molecular structure and function of the epithelial tight
      junction (TJ) and mechanisms of its dysregulation. METHODS: Molecular analysis of
      proteins involved in TJ assembly and their regulation was performed by western
      blotting and confocal microscopy correlated to electrophysiology. RESULTS: A
      complex alteration of the composition of epithelial TJ proteins (with more pore
      forming claudins like claudin-2 and a reduction in tightening claudins like
      claudin-3, -5 and -7) was found for protein expression and subcellular
      localisation, responsible for an increase in paracellular biotin-NHS uptake. In
      contrast, epithelial apoptosis was only moderately elevated (accounting for a
      minor portion of barrier defects) and epithelial gross lesions--for example, at
      cell extrusion zones, were absent. This TJ alteration was linked to an altered
      localisation/expression of proteins regulating TJ assembly, the polarity complex
      protein Par-3 and the serine-/threonine phosphatase PP-1. CONCLUSIONS: Changes in
      cell polarity proteins Par-3 and PP-1 are associated with altered expression and
      assembly of TJ proteins claudin-2, -3, -5 and -7 and ZO-1, causing paracellular
      leakage in active coeliac disease.

PMID- 21865403
TI  - Synergistic tumour suppressor activity of E-cadherin and p53 in a conditional
      mouse model for metastatic diffuse-type gastric cancer.
AB  - BACKGROUND: Gastric cancer is the second most frequent cause of death from cancer
      in the world, diffuse-type gastric cancer (DGC) exhibiting a poor prognosis.
      Germline mutations of CDH1, encoding E-cadherin, have been reported in hereditary
      DGC, and genetic and/or epigenetic alterations of CDH1 are frequently detected in
      sporadic DGC. Genetic alterations of TP53 are also frequently found in DGC. To
      examine the synergistic effect of the loss of E-cadherin and p53 on gastric
      carcinogenesis, a mouse line was established in which E-cadherin and p53 are
      specifically inactivated in the stomach parietal cell lineage. METHODS: Atp4b-Cre
      mice were crossed with Cdh1(loxP/loxP) and Trp53(loxP/loxP) mice, and the gastric
      phenotype of Atp4b-Cre(+);Cdh1(loxP/loxP);Trp53(loxP/loxP) double conditional
      knockout (DCKO) mice was examined. RESULTS: Non-polarised E-cadherin-negative
      parietal cells and proton pump-negative atypical foci were observed in DCKO mice.
      Intramucosal cancers and invasive cancers composed of poorly differentiated
      carcinoma cells and signet ring cells, histologically very similar to those in
      humans, were found from 6 to 9 months, respectively. Fatal DGC developed at 100%
      penetrance within a year, frequently metastasised to lymph nodes, and had
      tumourigenic activity in immunodeficient mice. Gene expression profiles of DGC in
      DCKO mice also resembled those of human DGC, and mesenchymal markers and
      epithelial-mesenchymal transition-related genes were highly expressed in mouse
      DGC as in human DGC. CONCLUSION: This mouse line is the first genetically
      engineered mouse model of DGC and is very useful for clarifying the mechanism
      underlying gastric carcinogenesis, and provides a new approach to the treatment
      and prevention of DGC.

PMID- 21865404
TI  - HIV, HSV-2 and syphilis among married couples in India: patterns of discordance
      and concordance.
AB  - OBJECTIVES: Differences in sexual networks probably explain the disparity in the
      scale of HIV epidemics in sub-Saharan Africa and India. HIV and sexually
      transmitted infection (STI) discordant couple studies provide insights into
      important aspects of these sexual networks. The authors quantify the role of male
      sexual behaviour in HIV transmission in married couples in India. METHODS: The
      authors analysed patterns of HIV and STI discordance in married couples from two
      community surveys in India: the National Family Health Study-3 for HIV-1 and the
      Centre for Global Health Research health check-up for HSV-2 and syphilis. A
      statistical model was used to estimate the fraction of infections introduced by
      each of the two partners. RESULTS: Only 0.8%, 16.0% and 3.5% of couples were
      infected (either partner or both) with HIV-1, HSV-2 and syphilis, respectively. A
      large proportion of infected couples were discordant (73.0%, 56.3% and 84.2% for
      HIV-1, HSV-2 and syphilis, respectively). This model estimated that, among
      couples with any STI, the male partner introduced the infection the majority of
      the time (HIV-1: 85.4%, HSV-2: 64.1%, syphilis: 75.0%). CONCLUSIONS: Male sexual
      activity outside of marriage appears to be a driving force for the Indian HIV/STI
      epidemic. Male client and female sex worker contacts should remain a primary
      target of the National AIDS Control Program in India.

PMID- 21865405
TI  - Lymphatic pump treatment enhances the lymphatic and immune systems.
AB  - The osteopathic medical profession has long advocated the use of osteopathic
      lymphatic pump treatments (LPT) to improve lymphatic circulation, reduce edema
      and combat infectious disease. However, until recently, there was no scientific
      evidence that LPT enhances function of the lymphatic and immune systems. This
      review discusses the physiological functions of the lymphatic system, the ability
      of LPT to increase lymph flow under normal and experimental conditions, the
      clinical benefits of LPT, current research models for the study of LPT and the
      potential mechanisms by which LPT enhances lymphatic and immune function.

PMID- 21865406
TI  - Effect and mechanism of erythropoietin on mesenchymal stem cell proliferation in
      vitro under the acute kidney injury microenvironment.
AB  - Erythropoietin (EPO) can stimulate the proliferation and protraction of
      endothelial progenitor cells, and plays an important role in the proliferation
      and differentiation of marrow-derived mesenchymal stem cells (mMSCs) under the
      acute kidney injury (AKI) microenvironment. In the present study, C57BL/6 mice
      mMSCs were isolated, and AKI mice models were prepared. The renal cortex was
      obtained to prepare the ischemia/reperfusion (I/R) kidney homogenate supernatant.
      P3-mMSCs were treated by different methods: one group was added only I/R kidney
      homogenate supernatant, and another contained different concentrations of EPO (1,
      5, 10, 50 IU/mL) in I/R kidney homogenate supernatant. The proliferation and
      apoptosis of mMSCs were detected by CCK-8 and TUNEL (terminal deoxynucleotidyl
      transferase dUTP nick end labeling), respectively. Expression of erythropoietin
      receptor (EPOR) and protein of the signal pathway related to
      proliferation/apoptosis were also examined. The results showed that the
      proliferation ability of mMSCs treated with I/R kidney homogenate supernatant
      decreased significantly, while the apoptosis percentage was significantly higher
      than that of the control. After intervention of EPO, their proliferation enhanced
      and the apoptosis percentage decreased. EPOR expression was positive in P3-mMSCs.
      EPO decreased the expression of caspase-3 of mMSCs under the AKI microenvironment
      in a dose- and time-dependent manner, but increased the Bcl-2 expression. The
      expression of phosphor-Janus kinase 2, phosphor-signal transducer and activator
      of transcription (pSTAT-5) increased significantly in 10 IU/mL EPO cultured for
      five days. Our results show that EPO can promote proliferation of mMSCs in vitro
      under the AKI microenvironment, which is mediated by EPOR and related with the
      proliferation/apoptosis signal pathway.

PMID- 21865407
TI  - Protective effect of zinc on N-methyl-N-nitrosourea and testosterone-induced
      prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague
      Dawley rats.
AB  - Previous studies have suggested that zinc exerts anticarcinogenic and
      antiproliferative effects against prostate cancer both in vitro and in rat
      ventral prostate. Zinc accumulation diminishes early in the course of prostate
      malignancy and it inhibits the growth of several carcinoma cells through
      induction of cell cycle arrest and apoptosis. In this study, we have investigated
      the influence of zinc on N-methyl-N-nitrosourea (MNU) and testosterone (T)
      induced prostatic intraepithelial neoplasia in the dorsolateral prostate of
      Sprague Dawley (SD) rats. The results indicate that zinc plays an important role
      in prostate carcinogenesis. Increased tumor incidence was accompanied by a
      decrease in prostatic acid phosphatase activity, citrate, zinc, glutathione-S
      transferase, reduced glutathione, p53, B-cell lymphoma protein (Bcl-2)-associated
      X protein and caspase-3 levels in MNU + T-treated rats. On the contrary,
      significantly increased phase I drug metabolizing enzyme activities, lipid
      peroxide, hydrogen peroxide, proliferating cell nuclear antigen, Bcl-2 and Bcl
      X(L) protein levels were observed in the dorsolateral prostate of MNU + T-treated
      rats. Simultaneous zinc supplementation significantly reversed these effects in
      MNU + T-treated rats. Signs of dysplasia, a characteristic of prostatic
      intraepithelial neoplasia, were evident in the dorsolateral prostatic tissue
      sections by MNU + T administration. However, zinc supplementation has reversed
      these effects in the dorsolateral prostatic histoarchitecture. These results
      suggest that zinc may act as an essential trace element against MNU and
      testosterone-induced prostatic preneoplastic progression in SD rats.

PMID- 21865408
TI  - Plasma omentin-1 levels are reduced in non-obese women with normal glucose
      tolerance and polycystic ovary syndrome.
AB  - OBJECTIVE: Omentin-1 is a novel adipokine that increases insulin sensitivity and
      is expressed in visceral adipose tissue. The aim of this study was to determine
      the metabolic parameters that influence plasma omentin-1 levels in women with
      polycystic ovary syndrome (PCOS). DESIGN AND METHODS: A cross-sectional study was
      performed in 87 women with PCOS and 53 body mass index (BMI)-matched healthy
      controls including 39 non-obese, normal-weight (NW) PCOS women with normal
      glucose tolerance (NGT) and 44 BMI- and homeostasis model assessment (HOMA)
      matched controls. Indices of insulin sensitivity, metabolic variables,
      circulating androgen levels, serum adiponectin, and omentin-1 levels were
      measured. A 75 g oral glucose tolerance test was performed in all participants.
      RESULTS: Plasma omentin-1 levels were significantly lower in women with PCOS
      compared with those in BMI-matched controls (P<0.001). A significantly lower
      level of plasma omentin-1 was observed in non-obese women with PCOS and NGT
      compared with that in BMI- and HOMA-matched controls (P<0.001). Omentin-1 level
      was negatively correlated with BMI, indices of insulin sensitivity, and
      circulating androgens and was associated with greater 2 h postprandial glucose, C
      peptide, and insulin levels compared with fasting values. Within the NW and NGT
      groups, omentin-1 levels remained negatively correlated with BMI, 2 h
      postprandial C-peptide, and circulating androgens and demonstrated a negative
      linear trend according to quartile of free testosterone (P=0.028). CONCLUSIONS:
      Plasma levels of omentin-1 were reduced in non-obese women with PCOS and NGT.
      Postprandial hyperinsulinemia and hyperglycemia contributed more to lower omentin
      1 levels than did fasting values in the setting of PCOS. Increased androgen
      levels contributed to decreased omentin-1 levels in women with PCOS.

PMID- 21865409
TI  - Body composition and quality of life in adults treated with GH therapy: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To summarise the evidence about the efficacy and safety of using GH in
      adults with GH deficiency focusing on quality of life and body composition. DATA
      SOURCES: We searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus
      through April 2011. We also reviewed reference lists and contacted experts to
      identify candidate studies. STUDY SELECTION: Reviewers, working independently and
      in duplicate, selected randomised controlled trials (RCTs) that compared GH to
      placebo. DATA SYNTHESIS: We pooled the relative risk (RR) and weighted mean
      difference (WMD) by the random effects model and assessed heterogeneity using the
      I(2) statistic. RESULTS: Fifty-four RCTs were included enrolling over 3400
      patients. The quality of the included trials was fair. GH use was associated with
      statistically significant reduction in weight (WMD, 95% confidence interval (95%
      CI): -2.31 kg, -2.66 and -1.96) and body fat content (WMD, 95% CI: -2.56 kg, 
      2.97 and -2.16); increase in lean body mass (WMD, 95% CI: 1.38, 1.10 and 1.65),
      the risk of oedema (RR, 95% CI: 6.07, 4.34 and 8.48) and joint stiffness (RR, 95%
      CI: 4.17, 1.4 and 12.38); without significant changes in body mass index, bone
      mineral density or other adverse effects. Quality of life measures improved in 11
      of the 16 trials although meta-analysis was not feasible. RESULTS: GH therapy in
      adults with confirmed GH deficiency reduces weight and body fat, increases lean
      body mass and increases oedema and joint stiffness. Most trials demonstrated
      improvement in quality of life measures.

PMID- 21865410
TI  - Treatment of relapsing-remitting multiple sclerosis with high-dose
      cyclophosphamide induction followed by glatiramer acetate maintenance.
AB  - BACKGROUND: Previous studies have described stabilization of aggressive multiple
      sclerosis (MS) with one-time induction therapy with high-dose cyclophosphamide
      (HiCy). The long-term benefit of this stabilization followed by conventional
      therapy has not been explored. OBJECTIVE: The objective of this study was to
      evaluate the safety and clinical outcomes following treatment of relapsing
      remitting MS with HiCy induction therapy followed by glatiramer acetate
      maintenance. METHODS: A retrospective review of a closely followed population of
      thirty two MS patients treated with HiCy (200mg/kg intravenous infusion over 4
      days) followed by maintenance with glatiramer acetate was performed. RESULTS:
      Annualized relapse rate was reduced from 1.37 in the 2 years prior to treatment
      to 0.27 over a mean post-treatment follow-up period of 14 months (range 0.5
      33.8). The projected probability of relapse-free survival at 2 years was 0.64
      (95% CI 0.37-0.82). The projected probability of Expanded Disability Status Scale
      (EDSS) progression-free survival at 2 years was 0.77 (95% CI 0.43-0.92). The mean
      number of gadolinium-enhanced lesions was reduced from 0.86 (SD 1.6) at baseline
      to 0 at 12 months and 0.08 (SD 0.28) at 15-24 months. A total of 55% of patients
      had no evidence of disease activity in follow-up. Infectious complications
      occurred in 47% with no long-term morbidity and no deaths. CONCLUSIONS: Induction
      therapy with HiCy followed by long-term maintenance with glatiramer acetate is
      well tolerated in patients with MS, and appears to be efficacious in reducing the
      risk of relapse, disability progression, and new MRI lesions.

PMID- 21865411
TI  - Visual dysfunction in multiple sclerosis correlates better with optical coherence
      tomography derived estimates of macular ganglion cell layer thickness than
      peripapillary retinal nerve fiber layer thickness.
AB  - BACKGROUND: Post-mortem analyses of multiple sclerosis (MS) eyes demonstrate
      prominent retinal neuronal ganglion cell layer (GCL) loss, in addition to related
      axonal retinal nerve fiber layer (RNFL) loss. Despite this, clinical correlations
      of retinal neuronal layers remain largely unexplored in MS. OBJECTIVES: To
      determine if MS patients exhibit in vivo retinal neuronal GCL loss, deeper
      retinal neuronal loss, and investigate correlations between retinal layer
      thicknesses, MS clinical subtype and validated clinical measures. METHODS: Cirrus
      HD-optical coherence tomography (OCT), utilizing automated intra-retinal layer
      segmentation, was performed in 132 MS patients and 78 healthy controls. MS
      classification, Expanded Disability Status Scale (EDSS) and visual function were
      recorded in study subjects. RESULTS: GCL+inner plexiform layer (GCIP) was thinner
      in relapsing-remitting MS (RRMS; n = 96, 71.6 um), secondary progressive MS
      (SPMS; n = 20, 66.4 um) and primary progressive MS (PPMS; n = 16, 74.1 um) than
      in healthy controls (81.8 um; p < 0.001 for all). GCIP thickness was most
      decreased in SPMS, and although GCIP thickness correlated significantly with
      disease duration, after adjusting for this, GCIP thickness remained significantly
      lower in SPMS than RRMS. GCIP thickness correlated significantly, and better than
      RNFL thickness, with EDSS, high-contrast, 2.5% low-contrast and 1.25% low
      contrast letter acuity in MS. 13.6% of patients also demonstrated inner or outer
      nuclear layer thinning. CONCLUSIONS: OCT segmentation demonstrates in vivo GCIP
      thinning in all MS subtypes. GCIP thickness demonstrates better structure
      function correlations (with vision and disability) in MS than RNFL thickness. In
      addition to commonly observed RNFL/GCIP thinning, retinal inner and outer nuclear
      layer thinning occur in MS.

PMID- 21865412
TI  - Age at onset as a determinant of presenting phenotype and initial relapse
      recovery in multiple sclerosis.
AB  - BACKGROUND: Age at onset modifies prognosis in multiple sclerosis (MS) and may
      also exert an effect on the characteristics of disease ignition. Understanding
      how age influences presentation informs disease management and may allow
      differentiation of distinct clinical sub-groups. OBJECTIVES: To determine the
      nature of age-specific presentations of relapsing-remitting MS (RRMS) with
      respect to onset symptoms, gender ratios and index event outcomes. METHODS: In a
      prospective, population-based sample of 1424 patients in South-East Wales we
      examined associations between age at onset, clinical features and outcome of the
      onset event, making specific comparisons between paediatric, adolescent and late
      onset MS. RESULTS: Age at onset varied significantly between sexes (Male 31.2,
      Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and
      2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and
      declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric
      symptoms rose with age independent of sex and disease course. F:M ratios were
      highest <16 years of age and declined with increasing age, with a male excess in
      those over 50. Probability of complete recovery from index event declined with
      age from 87.4% in the youngest group to 68% in the eldest (p = 0.009).
      CONCLUSIONS: Age at disease onset in RRMS exerts a significant effect on gender
      ratios and presenting phenotype, and allows identification of specific clinical
      sub-groups. In addition, ability to recover from initial relapse declines with
      age, suggesting accumulation of disability in MS is an age-dependent response to
      relapse.

PMID- 21865413
TI  - Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis
      in a Spanish cohort of patients with clinically isolated syndromes.
AB  - BACKGROUND: Recently the International Panel on Diagnosis of Multiple Sclerosis
      (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis
      of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate
      the accuracy of these new criteria for lesions dissemination in space (DIS) and
      time (DIT), from a single MRI scan, to predict conversion from CIS to clinically
      definite MS. METHODS: We studied 67 CIS patients with baseline MRI performed
      within the first 3 months after onset. The follow-up was of at least 24 months.
      The sensitivity, specificity and accuracy of Barkhof-Tintore criteria and the new
      proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0. RESULTS:
      The mean age for clinical onset was 30 years and 64% of patients were female. The
      overall conversion rate was 74%. In our cohort, Barkhof-Tintore criteria showed a
      sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New
      DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an
      accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan
      in 54 patients with baseline scans that included gadolinium-enhanced images. The
      sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy
      of 59.26%. CONCLUSION: New DIS criteria are simpler and more sensitive than
      previous criteria. The sensitivity of DIT criterion using a single MRI scan was
      rather low, as other previous studies showed, reflecting its stringency, but it
      could improve the accuracy of early MS diagnosis in that group of patients with
      typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline
      scans. These results reinforce their use in MS diagnosis.

PMID- 21865414
TI  - Comment on the article by Stauch et al. 'Intrathecal IgM synthesis in paediatric
      MS is not a negative prognostic marker of disease progression: quantitative
      versus qualitative IgM analysis'.

PMID- 21865415
TI  - Benign multiple sclerosis: a new definition of this entity is needed.
AB  - BACKGROUND: To study a cohort of benign multiple sclerosis (BMS) patients beyond
      physical disability, including the evaluation of cognitive and social function,
      as well as fatigue, pain and MRI studies. METHODS: A cohort of 342 patients was
      prospectively followed for 10.9 +/- 0.71 years. Forty-three patients (12.5%) met
      the BMS diagnosis criteria [Expanded Disability Status Scale (EDSS) < 3 after at
      least 10 years' disease duration], undergoing full neurological examination every
      6 months. Neuropsychological status, pain, fatigue, social functioning and work
      related disability, as well as brain MRIs, were assessed yearly. RESULTS: By the
      end of follow-up, 20 of 43 BMS patients (47%) had suffered cognitive impairment
      and 23 (53.3%) referred depression. Furthermore, 21 (48.8%) reported significant
      changes in pain intensity, with fatigue and environmental severity scores
      significantly increasing over time in 33-35% of patients. Finally, 32 BMS
      patients (74%) showed significant increase in the number of new or enlarging T2
      lesions, gadolinium-enhanced lesions, and persistent black holes, without changes
      in EDSS. Thirty-five of 43 patients (81%) fulfilling the BMS diagnostic criteria
      showed significant worsening of cognitive function, fatigue, pain or depression
      during the 10-year follow-up. CONCLUSIONS: Currently accepted criteria for BMS
      diagnosis may cause overestimation of true prevalence, underscoring the need for
      routine monitoring of non-motor symptoms and imaging studies, to help physicians
      improve diagnostic accuracy as well as therapeutic decision-making in this
      subgroup of MS patients.

PMID- 21865416
TI  - Poor diagnostic accuracy of commercial antibody-based assays for the diagnosis of
      acute Chikungunya infection.
AB  - A Sri Lankan fever cohort (n = 292 patients; 17.8% prevalence) was used to assess
      two standard diagnostic Chikungunya IgM tests. The immunochromatographic test
      (ICT) acute sample sensitivity (SN) was 1.9 to 3.9%, and specificity (SP) was
      92.5 to 95.0%. The enzyme-linked immunosorbent assay (ELISA) gave an acute sample
      SN of 3.9% and an SP of 92.5% and a convalescent sample SN of 84% and an SP of
      91%. These assays are not suitable for the acute diagnosis of Chikungunya virus
      infection.

PMID- 21865417
TI  - A rabbit vaginal cell-derived antimicrobial peptide, RVFHbalphaP, blocks
      lipopolysaccharide-mediated inflammation in human vaginal cells in vitro.
AB  - Antimicrobial peptides (AMPs) constitute a phylogenetically ancient form of
      innate immunity that provides host defense at various mucosal surfaces, including
      the vagina. Recently, we have identified one such AMP, rabbit vaginal fluid
      hemoglobin alpha peptide (RVFHbalphaP), from the vaginal lavage of rabbits
      (Oryctolagus cuniculus). The recent demonstration of a protective role of this
      peptide in erythrocytes and vaginal cells led us to investigate (i) the
      lipopolysaccharide (LPS) interactive domain in RVFHbalphaP and (ii) whether
      RVFHbalphaP of rabbit origin modulates the cellular immune responses of another
      species (humans) in vitro. HeLa-S3, a human vaginal epithelial cell line (hVEC),
      was exposed to LPS alone (10 MUg/ml for 6 h), or LPS-induced cells were treated
      with RVFHbalphaP (70.45 MUM for 1 h) and cultured for 24 h, and the results
      obtained were compared with the medium control. We show here that RVFHbalphaP
      exerts an anti-inflammatory activity in hVECs, as suggested by the prevention of
      LPS-induced production of extracellular (supernatant) and intracellular (lysate)
      levels of cytokines (interleukin 6 [IL-6] and IL-1alpha) and chemokines (IL-8 and
      monocyte chemoattractant protein 1 [MCP-1]). The demonstration of Toll-like
      receptor 4 (TLR4) and NF-kappaB expression in hVECs and the observations of
      RVFHbalphaP suppression of human beta-defensin-1 (hBD1) mRNA expression further
      support the hypothesis of a genomic activity of RVFHbalphaP. Confocal microscopy
      and flow cytometry results demonstrate that RVFHbalphaP inhibits LPS-induced
      phagocytosis of Escherichia coli by macrophages. The chemotaxis studies performed
      using the Boyden chamber Transwell method showed the increased migration of U937
      cells when supernatants of LPS-induced hVECs were used, and this effect was
      inhibited by RVFHbalphaP. In conclusion, our study proposes a novel explanation
      for the protective role of RVFHbalphaP in inflammation-associated infections,
      which not only may provide the new cellular targets for the screening of
      RVFHbalphaP ligands acting in the vaginal tissue but also has the potential to
      develop RVFHbalphaP as a therapeutic agent for reproductive tract infections.

PMID- 21865419
TI  - Comparison of two nucleic acid amplification assays, the Xpert MTB/RIF assay and
      the amplified Mycobacterium Tuberculosis Direct assay, for detection of
      Mycobacterium tuberculosis in respiratory and nonrespiratory specimens.
AB  - We compared the performance of the Xpert MTB/RIF assay, a new real-time
      tuberculosis (TB) PCR test, with that of the Amplified Mycobacterium Tuberculosis
      Direct (MTD) assay using 162 respiratory and nonrespiratory specimens. Based on
      culture as the gold standard, the overall sensitivity and specificity for all
      sample types for the Xpert MTB/RIF assay were 90.9 and 89%, respectively, while
      for the MTD assay, the overall sensitivity and specificity were 97.3 and 87.1%,
      respectively. A higher proportion of total equivocal results were obtained for
      the MTD assay, at 10.5% (17/162), while the Xpert MTB/RIF assay generated 5.5%
      (9/162) of invalid reads.

PMID- 21865418
TI  - A study of the genetic variability of human respiratory syncytial virus (HRSV) in
      Cambodia reveals the existence of a new HRSV group B genotype.
AB  - Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization
      of children aged <5 years due to respiratory illness in industrialized countries,
      and pneumonia is the leading cause of mortality among children aged <5 years
      worldwide. Although HRSV was first identified in 1956, a preventative vaccine has
      yet to be developed. Here we report the results of the first study to investigate
      the circulation and genetic diversity of HRSV in Cambodia among an all-ages
      population over 5 consecutive years. The incidences of HRSV infection among all
      ages outpatient and hospitalized populations were equivalent, at 9.5% and 8.2%,
      respectively. Infection was most prevalent among children aged <5 years, with
      bronchiolitis being the most frequently observed clinical syndrome in the same
      age group. Circulation of HRSV was seasonal, typically coinciding with the rainy
      season between July and November annually. Strains belonging to HRSV groups A and
      B were detected with equivalent frequencies; however, we observed a potentially
      biennial shift in the predominant circulating HRSV genotype. The majority of HRSV
      group B strains belonged to the recently described BA genotype, with the
      exception of 10 strains classified as belonging to a novel HRSV group B genotype,
      SAB4, first reported here.

PMID- 21865420
TI  - Predictors of relapse of methicillin-resistant Staphylococcus aureus bacteremia
      after treatment with vancomycin.
AB  - The risk factors for relapse of methicillin-resistant Staphylococcus aureus
      (MRSA) bacteremia after vancomycin treatment are unknown. Diversilab typing was
      used to classify recurrent bacteremia as relapse or reinfection. Bacteremia for
      >7 days and staphylococcal cassette chromosome mec element (SCCmec) type II were
      independently associated with relapse of MRSA bacteremia after vancomycin
      treatment.

PMID- 21865421
TI  - Saksenaea erythrospora infection following combat trauma.
AB  - Saksenaea erythrospora is a newly described species of the order Mucorales which
      has not previously been reported as a cause of human infection. We report a fatal
      case of S. erythrospora invasive burn wound infection in a 26-year-old male
      injured during combat operations in Iraq.

PMID- 21865422
TI  - Genetic heterogeneity in clinical isolates of Leishmania donovani from India.
AB  - Genetic diversity within 45 Indian Leishmania donovani isolates was analyzed
      using seven genetic markers. While kinetoplast DNA (kDNA) analysis revealed 15
      genotypes, 8 genotypes were obtained by analysis of other markers. In contrast to
      earlier reports, our data suggest that significant genetic polymorphisms exist in
      L. donovani strains in Bihar, India. Our results confirm the presence of 2
      zymodemes in India.

PMID- 21865423
TI  - Visual detection of high-risk human papillomavirus genotypes 16, 18, 45, 52, and
      58 by loop-mediated isothermal amplification with hydroxynaphthol blue dye.
AB  - A simple, rapid, sensitive, qualitative, colorimetric loop-mediated isothermal
      amplification (LAMP) with hydroxynaphthol blue dye (HNB) was established to
      detect high-risk human papillomavirus (HPV) genotypes 16, 18, 45, 52, and 58. All
      initial validation studies with the control DNA proved to be type specific. The
      colorimetric type-specific LAMP assay could achieve a sensitivity of 10 to 100
      copies at 63 degrees C for 65 min, comparable to that of real-time PCR. In order
      to evaluate the reliability of HPV type-specific LAMP, the assay was further
      evaluated with HPV DNAs from a panel of 294 clinical specimens whose HPV status
      was previously determined with a novel one-step typing method with multiplex PCR.
      The tested panel comprised 108 HPV DNA-negative samples and 186 HPV-DNA-positive
      samples of 14 genotypes. The results showed that the sensitivity of HPV type
      specific LAMP for HPV types 16, 18, 45, 52, and 58 was 100%, 100%, 100%, 100%,
      and 100%, respectively, and the specificity was 100%, 98.5%, 100%, 98.8%, and
      99.2%, respectively, compared with a novel one-step typing method with multiplex
      PCR. No cross-reactivity with other HPV genotypes was observed. In conclusion,
      this qualitative and colorimetric LAMP assay has potential usefulness for the
      rapid screening of HPV genotype 16, 18, 45, 52, and 58 infections, especially in
      resource-limited hospitals or rural clinics of provincial and municipal regions
      in China.

PMID- 21865424
TI  - Emergence of a novel Shiga toxin-producing Escherichia coli O serogroup cross
      reacting with Shigella boydii type 10.
AB  - This is the first report of the isolation of Shiga toxin-producing Escherichia
      coli (STEC) strains whose O antigens were genetically and serologically identical
      to those of Shigella boydii type 10, from human feces. The novel STEC O serogroup
      may be widespread in Japan and associated with diarrhea and hemorrhagic colitis.

PMID- 21865425
TI  - Clinical and molecular characteristics of invasive and noninvasive skin and soft
      tissue infections caused by group A Streptococcus.
AB  - The severity of skin and soft tissue infections caused by group A Streptococcus
      (GAS) is variable, and there are only a limited number of studies evaluating the
      characteristics of these infections in the literature. From May 2005 to November
      2007, 73 patients with skin and soft tissue infections caused by group A
      Streptococcus were included in this study. Among these patients, 34 (46.6%) had
      invasive diseases. Diabetes mellitus, alcoholism, and hypertension were the most
      common underlying disorders. The overall mortality rate was 6.8%, and the elderly
      were predisposed to invasive infections (P < 0.001). Neutrophil percentages of
      >=80, serum creatinine levels of >=2 mg/dl, and high serum C-reactive protein
      levels were noted more frequently in patients with invasive infections than in
      patients with noninvasive infections, as were bacteremia and a high mortality
      rate. Of the 73 isolates, 93.2%, 97.3%, and 37% exhibited susceptibility to
      erythromycin, clindamycin, and tetracycline, respectively. The five most
      prevalent emm types were emm106 (24.7%), emm11 (12.3%), emm102 (9.6%), emm4
      (8.2%), and emm12 (8.2%). Compared to other types, the emm106 type was
      significantly more likely to be associated with invasive diseases (P = 0.012).
      Dendrogram analysis showed a unique SmaI-digested pulsed-field gel
      electrophoresis pattern of the emm106 type that was particularly prone to cause
      invasive skin and soft tissue infections (P < 0.001). The results of this study
      suggest that isolates with the emm106 gene may be an emerging group A
      Streptococcus strain that causes invasive skin and soft tissue infections.
      Further surveillance study to understand the significance of this invasive strain
      is critical.

PMID- 21865426
TI  - External quality assessment for enterovirus 71 and coxsackievirus A16 detection
      by reverse transcription-PCR using armored RNA as a virus surrogate.
AB  - Three armored RNAs (virus-like particles [VLPs]) containing target sequences from
      enterovirus 71 (EV71) and coxsackievirus A16 (CA16) and a pan-enterovirus (pan
      EV) sequence were constructed and used in an external quality assessment (EQA) to
      determine the performance of laboratories in the detection of EV71 and CA16. The
      EQA panel, which consisted of 20 samples, including 14 positive samples with
      different concentrations of EV and either EV71 or CA16 armored RNAs, 2 samples
      with all 3 armored RNAs, and 4 negative-control samples (NaN(3)-preserved minimal
      essential medium [MEM] without VLPs), was distributed to 54 laboratories that
      perform molecular diagnosis of hand, foot, and mouth disease (HFMD) virus
      infections. A total of 41 data sets from 41 participants were returned; 5 (12.2%)
      were generated using conventional in-house reverse transcription-PCR (RT-PCR)
      assays, and 36 (87.8%) were generated using commercial real-time RT-PCR assays.
      Performance assessments of laboratories differed; 12 (29.3%) showed a need for
      improvement. Surprisingly, 4 laboratories were unable to detect EV71 RNA in any
      samples, even those containing the highest concentration of 10(7) IU/ml.
      Furthermore, the detection sensitivity for EV71 among all laboratories (82.1%)
      was substantially lower than that for EV (97.4%) or CA16 (95.1%). Overall, the
      results of the present study indicate that EQA should be performed periodically
      to help laboratories monitor their ability to detect HFMD viruses and to improve
      the comparability of results from different laboratories.

PMID- 21865427
TI  - Quantification of Clostridium difficile in antibiotic-associated-diarrhea
      patients.
AB  - Comparing culture- and non-culture-based methods for quantifying Clostridium
      difficile in antibiotic-associated-diarrhea patients, we found that the real-time
      PCR method correlated well with quantitative culture and was more sensitive. A
      positive association between the population levels of C. difficile and the
      presence of its toxins was found.

PMID- 21865428
TI  - Characterization of invasive and colonizing isolates of Streptococcus agalactiae
      in East African adults.
AB  - Ninety-five colonizing isolates and 74 invasive isolates of Streptococcus
      agalactiae from Kenyan adults were characterized by using capsular serotyping and
      multilocus sequence typing. Twenty-two sequence types clustering into five clonal
      complexes were found. Data support the view that S. agalactiae isolates belonging
      to a limited number of clonal complexes are invasive in adults worldwide.

PMID- 21865429
TI  - Diagnostic strategy used to establish etiologies of encephalitis in a prospective
      cohort of patients in England.
AB  - The laboratory diagnostic strategy used to determine the etiology of encephalitis
      in 203 patients is reported. An etiological diagnosis was made by first-line
      laboratory testing for 111 (55%) patients. Subsequent testing, based on
      individual case reviews, resulted in 17 (8%) further diagnoses, of which 12 (71%)
      were immune-mediated and 5 (29%) were due to infection. Seventy-five cases were
      of unknown etiology. Sixteen (8%) of 203 samples were found to be associated with
      either N-methyl-d-aspartate receptor or voltage-gated potassium channel complex
      antibodies. The most common viral causes identified were herpes simplex virus
      (HSV) (19%) and varicella-zoster virus (5%), while the most important bacterial
      cause was Mycobacterium tuberculosis (5%). The diagnostic value of testing
      cerebrospinal fluid (CSF) for antibody was assessed using 139 samples from 99
      patients, and antibody was detected in 46 samples from 37 patients. Samples
      collected at 14 to 28 days were more likely to be positive than samples taken 0
      to 6 days postadmission. Three PCR-negative HSV cases were diagnosed by the
      presence of virus-specific antibody in the central nervous system (CNS). It was
      not possible to make an etiological diagnosis for one-third of the cases; these
      were therefore considered to be due to unknown causes. Delayed sampling did not
      contribute to these cases. Twenty percent of the patients with infections with an
      unknown etiology showed evidence of localized immune activation within the CNS,
      but no novel viral DNA or RNA sequences were found. We conclude that a good
      standard of clinical investigation and thorough first-line laboratory testing
      allows the diagnosis of most cases of infectious encephalitis; testing for CSF
      antibodies allows further cases to be diagnosed. It is important that testing for
      immune-mediated causes also be included in a diagnostic algorithm.

PMID- 21865430
TI  - High-resolution melting approach to efficient identification and quantification
      of H275Y mutant influenza H1N1/2009 virus in mixed-virus-population samples.
AB  - The single-nucleotide variation 823C to T (His275Tyr), responsible for
      oseltamivir drug resistance has been detected in some isolates of the influenza
      A/H1N1/2009 virus. Early detection of the presence of this oseltamivir-resistant
      strain allows prompt consideration of alternative treatment options. An isolated
      probe-asymmetric amplification PCR (Roche LightCycler v2.0) and high-resolution
      melting (HRM) method using unlabeled probes and amplified products (Idaho
      LightScanner 32) was designed and optimized to detect and estimate the proportion
      of H275Y mutants in influenza A/H1N1/2009 virus samples. The lower limit of
      quantification within the linear range of PCR assay detection was 200
      copies/reaction. The melting peaks of the H275Y-specific unlabeled probe for the
      wild-type A/H1N1/2009 and H275Y mutant viruses were clearly distinguishable at
      65.5 degrees C and 69.0 degrees C, respectively, at various ratios of wild
      type/mutant virus population standards. The 95% detection limit for the 10%
      mutant sample pool was 1,200 copies/reaction (95% confidence interval, 669.7 to
      3,032.6 copies/reaction). This HRM assay was tested with 116 archived clinical
      specimens. The quantitative HRM results obtained with samples containing mixed
      mutant-wild-type virus populations, at threshold cycle (C(T)) values of <29,
      compared well to those obtained with a pyrosequencing method performed by an
      independent laboratory. The quantitative feature of this assay allows the
      proportions of mutant and wild-type viral populations to be determined, which may
      assist in the conventional clinical management of infected patients and
      potentially more preemptive clinical management. This validated quantitative HRM
      method, with its low running cost, is well positioned as a rapid, high-throughput
      screening tool for oseltamivir resistance mutations in influenza A/H1N1/2009
      virus-infected patients, with the potential to be adapted to other influenza
      virus species.

PMID- 21865431
TI  - Rapid multiplexed immunoassay for simultaneous serodiagnosis of HIV-1 and
      coinfections.
AB  - Diagnosis of opportunistic infections in HIV-infected individuals remains a major
      public health challenge, particularly in resource-limited settings. Here, we
      describe a rapid diagnostic system that delivers a panel of serologic immunoassay
      results using a single drop of blood, serum, or plasma. The system consists of
      disposable cartridges and a simple reader instrument, based on an innovative
      implementation of planar waveguide imaging technology. The cartridge incorporates
      a microarray of recombinant antigens and antibody controls in a fluidic channel,
      providing multiple parallel fluorescence immunoassay results for a single sample.
      This study demonstrates system performance by delivering antibody (Ab) reactivity
      results simultaneously for multiple antigens of HIV-1, Treponema pallidum
      (syphilis), and hepatitis C virus (HCV) in a collection of clinical serum,
      plasma, and whole-blood samples. By plotting antibody reactivity (fluorescence
      intensity) for known positive and negative samples, empirical reactivity cutoff
      values were defined. The HIV-1 assay shows 100% agreement with known
      seroreactivity for a collection of 82 HIV Ab-positive and 142 HIV Ab-negative
      samples, including multiple samples with HCV and syphilis coinfection. The
      treponema-specific syphilis assay correctly identifies 67 of 68 T. pallidum Ab
      positive and 100 of 102 T. pallidum Ab-negative samples, and the HCV assay
      correctly identifies 59 of 60 HCV Ab-positive and 120 of 121 HCV Ab-negative
      samples. Multiplexed assay performance for whole-blood samples is also
      demonstrated. The ability to diagnose HIV and opportunistic infections
      simultaneously at the point of care should lead to more effective therapy
      decisions and improved linkage to care.

PMID- 21865432
TI  - Evaluation of the DiversiLab typing method in a multicenter study assessing
      horizontal spread of highly resistant gram-negative rods.
AB  - The worldwide prevalence of highly resistant Gram-negative rods (HR-GNR) is
      increasing rapidly. Reliable typing methods are needed to detect and control
      outbreaks and to monitor the effectiveness of infection control programs in
      endemic situations. In this study, we investigated the performance of the
      DiversiLab typing method in comparison with the amplified fragment length
      polymorphism (AFLP) typing method. Six hundred fifty-three HR-GNR isolates, which
      were obtained during a 6-month prospective survey in 18 Dutch hospitals, were
      typed by AFLP and DiversiLab. Subsequently, the sensitivity and specificity of
      DiversiLab were calculated, using AFLP as the reference method. In addition,
      results were compared by means of epidemiological linkage, and Cohen's kappa for
      agreement was calculated. DiversiLab considered significantly more isolates (275)
      to belong to a cluster than AFLP (198) (P < 0.001). In direct comparison, the
      sensitivity was 83.8%, and the specificity was 78.6%. When epidemiological
      linkage was included in the analysis, DiversiLab considered eight isolates as
      secondary cases, which were considered unique in AFLP. Only two secondary cases,
      according to AFLP, were missed by DiversiLab. This results in a kappa for
      agreement of 0.985. In daily practice, a typing method has to be used in
      combination with epidemiological information. When this was done, DiversiLab was
      shown to be a reliable method for the typing of HR-GNR. This, in combination with
      the ease of use and the speed, makes DiversiLab an appropriate method for
      screening in routine clinical practice. When a cluster is suspected and the
      consequences of these findings are substantial, a confirmatory analysis should be
      performed.

PMID- 21865433
TI  - Effect of sample storage conditions on culture-independent bacterial community
      measures in cystic fibrosis sputum specimens.

PMID- 21865434
TI  - Pre- and postnatal differences in membrane, action potential, and ion channel
      properties of rostral nucleus of the solitary tract neurons.
AB  - There is little known about the prenatal development of the rostral nucleus of
      the solitary tract (rNST) neurons in rodents or the factors that influence
      circuit formation. With morphological and electrophysiological techniques in
      vitro, we investigated differences in the biophysical properties of rNST neurons
      in pre- and postnatal rats from embryonic day 14 (E14) through postnatal day 20.
      Developmental changes in passive membrane and action potential (AP) properties
      and the emergence and maturation of ion channels important in neuron function
      were characterized. Morphological maturation of rNST neurons parallels changes in
      passive membrane properties. Mean soma size, dendritic branch points, neurite
      endings, and neurite length all increase prenatally. whereas neuron resting
      membrane potential, input resistance, and time constant decrease. Dendritic
      spines, on the other hand, develop after birth. AP discharge patterns alter in
      pre- and postnatal stages. At E14, neurons generated a single TTX-sensitive,
      voltage-gated Na(+) AP when depolarized; a higher discharge rate appeared at
      older stages. AP amplitude, half-width, and rise and fall times all change during
      development. Responses to current injection revealed a number of voltage-gated
      conductances in embryonic rNST, including a hyperpolarization-activated inward
      current and a low-threshold Ca(2+) current that initiated Ca(2+) spikes. A
      hyperpolarization-activated, transient outward potassium current was also present
      in the developing neurons. Although the properties of these channels change
      during development, they are present before synapses form and therefore, can
      contribute to initial establishment of neural circuits, as well as to the
      changing electrophysiological properties in developing rNST neurons.

PMID- 21865435
TI  - A distinctive subpopulation of medial septal slow-firing neurons promote
      hippocampal activation and theta oscillations.
AB  - The medial septum-vertical limb of the diagonal band of Broca (MSvDB) is
      important for normal hippocampal functions and theta oscillations. Although many
      previous studies have focused on understanding how MSVDB neurons fire rhythmic
      bursts to pace hippocampal theta oscillations, a significant portion of MSVDB
      neurons are slow-firing and thus do not pace theta oscillations. The function of
      these MSVDB neurons, especially their role in modulating hippocampal activity,
      remains unknown. We recorded MSVDB neuronal ensembles in behaving rats, and
      identified a distinct physiologically homogeneous subpopulation of slow-firing
      neurons (overall firing <4 Hz) that shared three features: 1) much higher firing
      rate during rapid eye movement sleep than during slow-wave (SW) sleep; 2)
      temporary activation associated with transient arousals during SW sleep; 3) brief
      responses (latency 15~30 ms) to auditory stimuli. Analysis of the fine temporal
      relationship of their spiking and theta oscillations showed that unlike the theta
      pacing neurons, the firing of these "pro-arousal" neurons follows theta
      oscillations. However, their activity precedes short-term increases in
      hippocampal oscillation power in the theta and gamma range lasting for a few
      seconds. Together, these results suggest that these pro-arousal slow-firing MSvDB
      neurons may function collectively to promote hippocampal activation.

PMID- 21865436
TI  - CCL2 has similar excitatory effects to TNF-alpha in a subgroup of inflamed C
      fiber axons.
AB  - Peripheral nerve inflammation can cause neuronal excitability changes that have
      been implicated in the pathogenesis of chronic pain. Although the neuroimmune
      interactions that lead to such physiological changes are unclear, in vitro
      studies suggest that the chemokine CCL2 may be involved. This in vivo study
      examines the effects of CCL2 on untreated and inflamed neurons and compares its
      effects with those of TNF-alpha. Extracellular recordings were performed in the
      anesthetized rat on isolated neurons with C-fiber axons. On untreated neurons,
      CCL2, as well as TNF-alpha, had negligible effects. Following neuritis, both
      cytokines transiently caused the firing of action potentials in 27-30% of
      neurons, which were either silent or had background (ongoing) activity. The
      neurons with ongoing activity, which responded to either cytokine, had
      significantly slower baseline firing rates {median = 3.0 spikes/min
      [interquartile range (IQR) 3.0]} compared with the nonresponders [median = 24.4
      spikes/min (IQR 24.6); P < 0.001]. In an additional group, 26-27% of neurons,
      which were sensitized due to repeated noxious mechanical stimulation of the
      periphery, also responded to the effects of both cytokines. Neither cytokine
      caused axons to become mechanically sensitive. Immunohistochemistry confirmed
      that the cognate CCL2 receptor, CCR2, is mainly expressed on glia and is
      therefore not likely to be an axonal target for CCL2 following inflammation. In
      contrast, the cognate TNF-alpha receptor (TNFR), TNFR1, was present on untreated
      and inflamed neurons. In summary, CCL2 can excite inflamed C-fiber neurons with
      similar effects to TNF-alpha, although the underlying mechanisms may be
      different. The modulatory effects of both cytokines are limited to a subgroup of
      neurons, which may be subtly inflamed.

PMID- 21865437
TI  - Modulation and transmission of peripheral inputs in monkey cuneate and external
      cuneate nuclei.
AB  - Somatosensory signals undergo substantial modulation in the dorsal column nuclei.
      We examined transmission of signals from forelimb afferents in primate cuneate
      and external cuneate nuclei. In anesthetized macaque monkeys, the median, ulnar,
      deep radial, and superficial radial nerves were electrically stimulated at 1.5-2*
      motor threshold with independent Poisson trains whereas extracellular recordings
      were made from 317 cells. Responses to peripheral stimulation included instances
      of both brief facilitation and long lasting suppression. A high proportion of
      cells (87%) responded to stimulation of two or more peripheral nerves, suggesting
      a large amount of convergence. Facilitated cells showed coherence with the
      peripheral stimulation across a broad frequency range; coherence was especially
      high in cells that responded with a burst of action potentials. Cells that
      responded with suppression also showed significant coherence, but this fell
      rapidly for frequencies above 25 Hz. Similar results were seen in both the main
      and external cuneate. When stimulation of one nerve was conditioned by a
      preceding nerve stimulus, the response to the second stimulus was attenuated for
      around 40 ms. This occurred independently of whether the first stimulus produced
      an initial facilitation or suppression or whether the same or a different nerve
      served as a conditioning stimulus. Mechanical stimulation of a receptive field
      suppressed responses to a second identical mechanical stimulus over a similar
      timescale. We conclude that the primate cuneate nucleus is capable of
      transmitting temporal information about stimuli with high fidelity; stimuli
      interact both temporally and spatially to modulate the onward transmission of
      information.

PMID- 21865438
TI  - Functional role of exercise-induced cortical organization of sensorimotor cortex
      after spinal transection.
AB  - Spinal cord transection silences neuronal activity in the deafferented cortex to
      cutaneous stimulation of the body and untreated animals show no improvement in
      functional outcome (weight-supported stepping) with time after lesion. However,
      adult rats spinalized since neonates that receive exercise therapy exhibit
      greater functional recovery and exhibit more cortical reorganization. This
      suggests that the change in the somatotopic organization of the cortex may be
      functionally relevant. To address this issue, we chronically implanted arrays of
      microwire electrodes into the infragranular layers of the hindlimb somatosensory
      cortex of adult rats neonatally transected at T8/T9 that received exercise
      training (spinalized rats) and of normal adult rats. Multiple, single neuron
      activity was recorded during passive sensory stimulation, when the animals were
      anesthetized, and during active sensorimotor stimulation during treadmill-induced
      locomotion when the animal was awake and free to move. Our results demonstrate
      that cortical neurons recorded from the spinalized rats that received exercise 1)
      had higher spontaneous firing rates, 2) were more likely to respond to both
      sensory and sensorimotor stimulations of the forelimbs, and also 3) responded
      with more spikes per stimulus than those recorded from normal rats, suggesting
      expansion of the forelimb map into the hindlimb map. During treadmill locomotion
      the activity of neurons recorded from neonatally spinalized rats was greater
      during weight-supported steps on the treadmill compared with the neuronal
      activity during nonweight supported steps. We hypothesize that this increased
      activity is related to the ability of the animal to take weight supported steps
      and that, therefore, these changes in cortical organization after spinal cord
      injury are relevant for functional recovery.

PMID- 21865439
TI  - Reversal of isoflurane-induced depression of myocardial contraction by nitroxyl
      via myofilament sensitization to Ca2+.
AB  - Isoflurane (ISO) is known to depress cardiac contraction. Here, we hypothesized
      that decreasing myofilament Ca(2+) responsiveness is central to ISO-induced
      reduction in cardiac force development. Moreover, we also tested whether the
      nitroxyl (HNO) donor 1-nitrosocyclohexyl acetate (NCA), acting as a myofilament
      Ca(2+) sensitizer, restores force in the presence of ISO. Trabeculae from the
      right ventricles of LBN/F1 rats were superfused with Krebs-Henseleit solution at
      room temperature, and force and intracellular Ca(2+) ([Ca(2+)](i)) were measured.
      Steady-state activations were achieved by stimulating the muscles at 10 Hz in the
      presence of ryanodine. The same muscles were chemically skinned with 1% Triton X
      100, and the force-Ca(2+) relation measurements were repeated. ISO depressed
      force in a dose-dependent manner without significantly altering [Ca(2+)](i). At
      1.5%, force was reduced over 50%, whereas [Ca(2+)](i) remained unaffected. At 3%,
      contraction was decreased by ~75% with [Ca(2+)](i) reduced by only 15%. During
      steady-state activation, 1.5% ISO depressed maximal Ca(2+)-activated force
      (F(max)) and increased the [Ca(2+)](i) required for 50% activation (Ca(50))
      without affecting the Hill coefficient. After skinning, the same muscles showed
      similar decreases in F(max) and increases in Ca(50) in the presence of ISO. NCA
      restored force in the presence of ISO without affecting [Ca(2+)](i). These
      results show that 1) ISO depresses cardiac force development by decreasing
      myofilament Ca(2+) responsiveness, and 2) myofilament Ca(2+) sensitization by NCA
      can effectively restore force development without further increases in
      [Ca(2+)](i). The present findings have potential translational value because of
      the efficiency and efficacy of HNO on ISO-induced myocardial contractile
      dysfunction.

PMID- 21865440
TI  - Hydrogen sulfide regulates Na+/H+ exchanger activity via stimulation of
      phosphoinositide 3-kinase/Akt and protein kinase G pathways.
AB  - Intracellular pH (pH(i)) is an important endogenous modulator of cardiac
      function. Inhibition of Na(+)/H(+) exchanger-1 (NHE-1) protects the heart by
      preventing Ca(2+) overload during ischemia/reperfusion. Hydrogen sulfide (H(2)S)
      has been reported to produce cardioprotection. The present study was designed to
      investigate the pH regulatory effect of H(2)S in rat cardiac myocytes and
      evaluate its contribution to cardioprotection. It was found that sodium
      hydrosulfide (NaHS), at a concentration range of 10 to 1000 MUM, produced
      sustained decreases in pH(i) in the rat myocytes in a concentration-dependent
      manner. NaHS also abolished the intracellular alkalinization caused by trans-(+/
      )-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methane
      sulfonate hydrate (U50,488H), which activates NHEs. Moreover, when measured with
      an NHCl(4) prepulse method, NaHS was found to significantly suppress NHE-1
      activity. Both NaHS and cariporide or [5-(2-methyl-5-fluorophenyl)furan-2
      ylcarbonyl]guanidine (KR-32568), two NHE inhibitors, protected the myocytes
      against ischemia/reperfusion injury. However, coadministration of NaHS with KR
      32568 did not produce any synergistic effect. Functional study showed that
      perfusion with NaHS significantly improved postischemic contractile function in
      isolated rat hearts subjected to ischemia/reperfusion. Blockade of
      phosphoinositide 3-kinase (PI3K) with 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran
      4-one (LY294002), Akt with Akt VIII, or protein kinase G (PKG) with (9S,10R,12R)
      2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H
      diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]]enzodiazocine-10-carboxylic
      acid, methyl ester (KT5823) significantly attenuated NaHS-suppressed NHE-1
      activity and/or NaHS-induced cardioprotection. Although KT5823 failed to affect
      NaHS-induced Akt phosphorylation, Akt inhibitor did attenuate NaHS-stimulated PKG
      activity. In conclusion, this work demonstrated for the first time that H(2)S
      produced cardioprotection via the suppression of NHE-1 activity involving a
      PI3K/Akt/PKG-dependent mechanism.

PMID- 21865441
TI  - Competitive enzymatic interactions determine the relative amounts of
      prostaglandins E2 and D2.
AB  - Prostaglandins (PGs) are a family of cellular messengers exerting diverse
      homeostatic and pathophysiologic effects. Recently, several studies reported
      significant increases of PGI(2) and PGF(2alpha) after the inhibition of
      microsomal PGE synthase-1 (mPGES-1) expression, which indicated that PGH(2)
      metabolism might be redistributed when the PGE(2) pathway is blocked. To address
      the determinants that govern the relative amounts of PGs, we developed an in
      vitro cell-free method, based on liquid chromatography-tandem mass spectrometry,
      to measure the exact amounts of these PGs formed in response to the addition of
      recombinant isomerases and their selective inhibitors. Our in vitro cell-free
      assay results were confirmed in cells using bone marrow-derived macrophage.
      Initially, we determined the in vitro stability of PGH(2) and noted that there
      was spontaneous nonenzymatic conversion to PGD(2) and PGE(2). mPGES-1 markedly
      increased the conversion to PGE(2) and decreased conversion to PGD(2).
      Reciprocally, the addition of hematopoietic or lipocalin PGD synthase resulted in
      a relative increase of PGD(2) and decrease of PGE(2). A detailed titration study
      showed that the ratio of PGE(2)/PGD(2) was closely correlated with the ratio of
      PGE synthase/PGD synthase. Our redistribution results also provide the foundation
      for understanding how PGH(2) metabolism is redistributed by the presence of
      distal isomerases or by blocking the major metabolic outlet, which could
      determine the relative benefits and risks resulting from interdiction in nonrated
      limiting components of PG synthesis pathways.

PMID- 21865442
TI  - Characterization of self-assembled virus-like particles of rat hepatitis E virus
      generated by recombinant baculoviruses.
AB  - Hepatitis E virus (HEV) is a causative agent of hepatitis E. Recently, a novel
      hepatitis E-like virus was isolated from Norway rats in Germany. However, the
      antigenicity, pathogenicity and epidemiology of this virus are unclear because of
      the lack of a cell-culture system in which to grow it. In this study, an N
      terminally truncated ORF2 protein was expressed in insect Tn5 cells using a
      recombinant baculovirus expression system and a large amount of 53 kDa protein
      was expressed and efficiently released into the supernatant. Electron microscopic
      analyses of the purified 53 kDa protein revealed that the protein self-assembled
      into two types of empty HEV-like particles (rat HEVLPs). The smaller rat HEVLPs
      were estimated to be 24 nm in diameter, which is similar to the size of genotype
      G1, G3 and G4 HEVLPs. The larger rat HEVLPs were estimated to measure 35 nm in
      diameter, which is similar to the size of native rat HEV particles. An ELISA to
      detect antibodies was established using rat HEVLPs as the antigens, which
      demonstrated that rat HEVLPs were cross-reactive with G1, G3 and G4 HEVs.
      Detection of IgG and IgM antibodies was performed by examination of 139 serum
      samples from wild rats trapped in Vietnam, and it was found that 20.9 % (29/139)
      and 3.6 % (5/139) of the samples were positive for IgG and IgM, respectively. In
      addition, rat HEV RNA was detected in one rat serum sample that was positive for
      IgM. These results indicated that rat HEV is widespread and is transmitted among
      wild rats.

PMID- 21865443
TI  - Recent advances in the molecular and cellular biology of bunyaviruses.
AB  - The family Bunyaviridae of segmented, negative-stranded RNA viruses includes over
      350 members that infect a bewildering variety of animals and plants. Many of
      these bunyaviruses are the causative agents of serious disease in their
      respective hosts, and are classified as emerging viruses because of their
      increased incidence in new populations and geographical locations throughout the
      world. Emerging bunyaviruses, such as Crimean-Congo hemorrhagic fever virus,
      tomato spotted wilt virus and Rift Valley fever virus, are currently attracting
      great interest due to migration of their arthropod vectors, a situation possibly
      linked to climate change. These and other examples of continued emergence suggest
      that bunyaviruses will probably continue to pose a sustained global threat to
      agricultural productivity, animal welfare and human health. The threat of
      emergence is particularly acute in light of the lack of effective preventative or
      therapeutic treatments for any of these viruses, making their study an important
      priority. This review presents recent advances in the understanding of the
      bunyavirus life cycle, including aspects of their molecular, cellular and
      structural biology. Whilst special emphasis is placed upon the emerging
      bunyaviruses, we also describe the extensive body of work involving model
      bunyaviruses, which have been the subject of major contributions to our overall
      understanding of this important group of viruses.

PMID- 21865444
TI  - The large Rep protein of adeno-associated virus type 2 is polyubiquitinated.
AB  - Five adenovirus (Ad) gene products are required for efficient replication of co
      infecting adeno-associated virus (AAV); however, the combined net enhancement by
      these factors is composed of both positive and negative effects. Similar to
      previous results with AAV Rep52, AAV2 large Rep was targeted for ubiquitination
      and degradation by the Ad E4orf6/E1b 55 kDa, cullin 5-containing, E3-ubiquitin
      ligase. Additionally, large Rep was targeted for ubiquitination via extension of
      ubiquitin lysine K48 and K63 both in the presence and absence of E4orf6.

PMID- 21865445
TI  - Envelope and pre-membrane protein structural amino acid mutations mediate
      diminished avian growth and virulence of a Mexican West Nile virus isolate.
AB  - The hallmark attribute of North American West Nile virus (WNV) strains has been
      high pathogenicity in certain bird species. Surprisingly, this avian virulent WNV
      phenotype has not been observed during its geographical expansion into the
      Caribbean, Central America and South America. One WNV variant (TM171-03-pp1)
      isolated in Mexico has demonstrated an attenuated phenotype in two widely
      distributed North American bird species, American crows (AMCRs) and house
      sparrows (HOSPs). In order to identify genetic determinants associated with
      attenuated avian replication of the TM171-03-pp1 variant, chimeric viruses
      between the NY99 and Mexican strains were generated, and their replicative
      capacity was assessed in cell culture and in AMCR, HOSP and house finch avian
      hosts. The results demonstrated that mutations in both the pre-membrane (prM
      I141T) and envelope (E-S156P) genes mediated the attenuation phenotype of the WNV
      TM171-03-pp1 variant in a chicken macrophage cell line and in all three avian
      species assayed. Inclusion of the prM-I141T and E-S156P TM171-03-pp1 mutations in
      the NY99 backbone was necessary to achieve the avian attenuation level of the
      Mexican virus. Furthermore, reciprocal incorporation of both prM-T141I and E
      P156S substitutions into the Mexican virus genome was necessary to generate a
      virus that exhibited avian virulence equivalent to the NY99 virus. These
      structural changes may indicate the presence of new evolutionary pressures
      exerted on WNV populations circulating in Latin America or may signify a genetic
      bottleneck that has constrained their epiornitic potential in alternative
      geographical locations.

PMID- 21865446
TI  - Rehabilitation interventions.

PMID- 21865447
TI  - Pulsed radiofrequency versus conventional transcutaneous electrical nerve
      stimulation in painful shoulder: a prospective, randomized study - can you really
      have the conclusion?

PMID- 21865449
TI  - p38alpha and p38beta mitogen-activated protein kinases determine cholinergic
      transdifferentiation of sympathetic neurons.
AB  - Although the p38 mitogen-activated protein kinases are active in many neuronal
      populations in the peripheral and central nervous systems, little is known about
      the physiological functions of p38 in postmitotic neurons. We report that p38
      activity determines in vitro and in vivo the switch from noradrenergic to
      cholinergic neurotransmission that occurs in sympathetic neurons on exposure to
      the neuropoietic cytokines CNTF and LIF. This transdifferentiation serves as a
      model for the plastic mechanisms that enable mature neurons to change some of
      their central functions without passing through the cell cycle. We demonstrate
      that in postmitotic neurons, p38 and STAT pathways are concurrently activated by
      neuropoietic cytokine treatment for at least 12 h overlapping with changes in
      neurotransmitter marker gene expression. Inhibition of p38 blocks the
      upregulation of the nuclear matrix protein Satb2 and of cholinergic markers by
      CNTF without affecting STAT3 phosphorylation. Conversely, overexpression of
      p38alpha or beta in the absence of cytokines stimulates cholinergic marker
      expression. The neurotransmitter switch in vitro is impaired in neurons isolated
      from p38beta(-/-) mice. Consistent with these in vitro results, a substantial
      loss of cells expressing cholinergic properties is observed in vivo in the
      stellate ganglion of mature mice deficient in the p38beta isoform.

PMID- 21865450
TI  - Bone morphogenetic protein inhibition promotes neurological recovery after
      intraventricular hemorrhage.
AB  - Intraventricular hemorrhage (IVH) results in neural cell death and white matter
      injury in premature infants. No therapeutic strategy is currently available
      against this disorder. Bone morphogenetic protein (BMP) signaling suppresses
      oligodendrocyte development through basic-helix-loop-helix (bHLH) transcription
      factors and promotes astrocytosis. Therefore, we hypothesized that IVH in
      premature newborns initiates degeneration and maturation arrest of
      oligodendrocyte lineage and that BMP inhibition alleviates hypomyelination,
      gliosis, and motor impairment in the survivors of IVH. To test the hypotheses, a
      rabbit model of IVH was used in which premature rabbit pups (E29) are treated
      with intraperitoneal glycerol at 2 h of age to induce IVH; and the pups with IVH
      exhibit hypomyelination and gliosis at 2 weeks of postnatal age. Maturation of
      oligodendrocyte lineage was evaluated by specific markers, and the expression of
      bHLH transcription factors was assessed. BMP levels were measured in both
      premature rabbit pups and autopsy materials from premature infants. Recombinant
      human noggin was used to suppress BMP action; and neurobehavioral performance,
      myelination and gliosis were assessed in noggin-treated pups compared with
      untreated controls. We found that IVH resulted in apoptosis and reduced
      proliferation of oligodendrocyte progenitors, as well as arrested maturation of
      preoligodendrocytes in rabbits. BMP4 levels were significantly elevated in both
      rabbit pups and human premature infants with IVH compared with controls.
      Importantly, BMP inhibition by recombinant human noggin restored the levels of
      phospho-Smad1/5/8, Olig2 transcription factor, oligodendrocyte maturation,
      myelination, astrocyte morphology, and motor function in premature pups with IVH.
      Hence, BMP inhibition might enhance neurological recovery in premature infants
      with IVH.

PMID- 21865451
TI  - Synaptic autoregulation by metalloproteases and gamma-secretase.
AB  - The proteolytic machinery comprising metalloproteases and gamma-secretase, an
      intramembrane aspartyl protease involved in Alzheimer's disease, cleaves several
      substrates in addition to the extensively studied amyloid precursor protein. Some
      of these substrates, such as N-cadherin, are synaptic proteins involved in
      synapse remodeling and maintenance. Here we show, in rats and mice, that
      metalloproteases and gamma-secretase are physiologic regulators of synapses. Both
      proteases are synaptic, with gamma-secretase tethered at the synapse by delta
      catenin, a synaptic scaffolding protein that also binds to N-cadherin and,
      through scaffolds, to AMPA receptor and a metalloprotease. Activity-dependent
      proteolysis by metalloproteases and gamma-secretase takes place at both sides of
      the synapse, with the metalloprotease cleavage being NMDA receptor-dependent.
      This proteolysis decreases levels of synaptic proteins and diminishes synaptic
      transmission. Our results suggest that activity-dependent substrate cleavage by
      synaptic metalloproteases and gamma-secretase modifies synaptic transmission,
      providing a novel form of synaptic autoregulation.

PMID- 21865452
TI  - Maintenance of dendritic spine morphology by partitioning-defective 1b through
      regulation of microtubule growth.
AB  - Dendritic spines are postsynaptic structures that receive excitatory synaptic
      input from presynaptic terminals. Actin and its regulatory proteins play a
      central role in morphogenesis of dendritic spines. In addition, recent studies
      have revealed that microtubules are indispensable for the maintenance of mature
      dendritic spine morphology by stochastically invading dendritic spines and
      regulating dendritic localization of p140Cap, which is required for actin
      reorganization. However, the regulatory mechanisms of microtubule dynamics remain
      poorly understood. Partitioning-defective 1b (PAR1b), a cell polarity-regulating
      serine/threonine protein kinase, is thought to regulate microtubule dynamics by
      inhibiting microtubule binding of microtubule-associated proteins. Results from
      the present study demonstrated that PAR1b participates in the maintenance of
      mature dendritic spine morphology in mouse hippocampal neurons. Immunofluorescent
      analysis revealed PAR1b localization in the dendrites, which was concentrated in
      dendritic spines of mature neurons. PAR1b knock-down cells exhibited decreased
      mushroom-like dendritic spines, as well as increased filopodia-like dendritic
      protrusions, with no effect on the number of protrusions. Live imaging of
      microtubule plus-end tracking proteins directly revealed decreases in distance
      and duration of microtubule growth following PAR1b knockdown in a neuroblastoma
      cell line and in dendrites of hippocampal neurons. In addition, reduced
      accumulation of GFP-p140Cap in dendritic protrusions was confirmed in PAR1b knock
      down neurons. In conclusion, the present results suggested a novel function for
      PAR1b in the maintenance of mature dendritic spine morphology by regulating
      microtubule growth and the accumulation of p140Cap in dendritic spines.

PMID- 21865453
TI  - Fast and slow gamma rhythms are intrinsically and independently generated in the
      subiculum.
AB  - Gamma rhythms are essential for memory encoding and retrieval. Despite extensive
      study of these rhythms in the entorhinal cortex, dentate gyrus, CA3, and CA1,
      almost nothing is known regarding their generation and organization in the
      structure delivering the most prominent hippocampal output: the subiculum. Here
      we show using a complete rat hippocampal preparation in vitro that the subiculum
      intrinsically and independently generates spontaneous slow (25-50 Hz) and fast
      (100-150 Hz) gamma rhythms during the rising phase and peak of persistent
      subicular theta rhythms. These two gamma frequencies are phase modulated by theta
      rhythms without any form of afferent input from the entorhinal cortex or CA1.
      Subicular principal cells and interneurons phase lock to both fast and slow
      gamma, and single cells are independently phase modulated by each form of gamma
      rhythm, enabling selective participation in neural synchrony at both gamma
      frequencies at different times. Fast GABAergic inhibition is required for the
      generation of fast gamma, whereas slow gamma is generated by excitatory and
      inhibitory mechanisms. In addition, the transverse subicular axis exhibits gamma
      rhythm topography with faster gamma coupling arising in the distal subiculum
      region. The subiculum therefore possesses a unique intrinsic circuit organization
      that can autonomously regulate the timing and topography of hippocampal output
      synchronization. These results suggest the subiculum is a third spontaneous gamma
      generator in the hippocampal formation (in addition to CA3 and the entorhinal
      cortex), and these gamma rhythms likely play an active role in mediating the flow
      of information between the hippocampus and multiple cortical and subcortical
      brain regions.

PMID- 21865454
TI  - Cyclin B1 expression regulated by cytoplasmic polyadenylation element binding
      protein in astrocytes.
AB  - Astrocytes are the most abundant cells in the brain, playing vital roles in
      neuronal survival, growth, and function. Understanding the mechanism(s)
      regulating astrocyte proliferation will have important implications in brain
      development, response to injury, and tumorigenesis. Cyclin B1 is well known to be
      a critical regulator of mitotic entry via its interaction with cyclin-dependent
      kinase 1. In rat astrocytes, we now show that the mRNA binding protein
      cytoplasmic polyadenylation element binding protein 1 (CPEB1) is associated with
      cyclin B1 mRNA and that this interaction is enriched at the centrosome. In
      addition, if growth-arrested astrocytes are stimulated to divide, CPEB1 is
      phosphorylated and cyclin B1 mRNA is polyadenylated, both hallmarks of CPEB1
      activation, resulting in an increase in cyclin B1 protein. CPEB1 binding to mRNA
      initially inhibits translation; therefore, removing CPEB1 from mRNA should result
      in an increase in translation due to derepression. Indeed, when we either knocked
      down CPEB1 protein with siRNA or sequestered it from endogenous mRNA by
      expressing RNA containing multiple CPEB1 binding sites, cyclin B1 protein was
      increased and cell proliferation was stimulated. Our data suggest a mechanism
      wherein CPEB1 is bound and represses cyclin B1 mRNA translation until a signal to
      proliferate phosphorylates CPEB1, resulting in an increase in cyclin B1 protein
      and progression into mitosis. Our results demonstrate for the first time a role
      for CPEB1 in regulating cell proliferation in the brain.

PMID- 21865455
TI  - Loss of PSD-95 enrichment is not a prerequisite for spine retraction.
AB  - Changes in neuronal structure are thought to underlie long-term behavioral
      modifications associated with learning and memory. In particular, considerable
      evidence implicates the destabilization and retraction of dendritic spines along
      with the loss of spine synapses as an important cellular mechanism for refining
      brain circuits, yet the molecular mechanisms regulating spine elimination remain
      ill-defined. The postsynaptic density protein, PSD-95, is highly enriched in
      dendritic spines and has been associated with spine stability. Because spines
      with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to
      nascent spines has been associated with spine stabilization, we hypothesized that
      loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test
      this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor
      rat hippocampal pyramidal neurons cotransfected with PSD-95-GFP and DsRed
      Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine
      morphological changes. Consistent with our hypothesis, we found that the majority
      of spines that retracted were relatively unenriched for PSD-95-GFP. However, in
      the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss
      of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment
      did not precede spine retraction. Moreover, we found that, in some instances,
      spine retraction resulted in a significant enrichment of PSD-95-GFP on the
      dendritic shaft. Our data support a model of spine retraction in which loss of
      PSD-95 enrichment is not required prior to the destabilization of spines.

PMID- 21865456
TI  - Effects of training of processing speed on neural systems.
AB  - Processing speed (PS) training improves performance on untrained PS tasks in the
      elderly. However, PS training's effects on the PS of young adults and on neural
      mechanisms are still unknown. In humans, we investigated this issue using
      psychological measures, voxel-based morphometry, the n-back task [a typical task
      for functional magnetic resonance imaging (fMRI) studies with conditions of 0
      back (simple cognitive processes) and 2-back tasks (working memory; WM)], resting
      state fMRI for the analysis of functional connectivity between brain regions
      during rest (resting-FC), and intensive adaptive training of PS. PS training was
      associated with (1) significant or substantial improvement in the performance of
      PS measures, (2) changes in the gray matter structures of the left superior
      temporal gyrus and the bilateral regions around the occipitotemporal junction,
      (3) changes in functional activity that are related to simple cognitive processes
      (but not those of WM) in the left perisylvian region, and (4) increased resting
      FC between the left perisylvian area and the area that extends to the lingual
      gyrus and calcarine cortex. These results confirm the PS-training-induced
      plasticity in PS and the training-induced plasticity of functions and structures
      that are associated with speeded cognitive processes. The observed neural changes
      caused by PS training may give us new insights into how PS training, and possibly
      other cognitive training, can improve PS.

PMID- 21865457
TI  - Complementary sensory and associative microcircuitry in primary olfactory cortex.
AB  - The three-layered primary olfactory (piriform) cortex is the largest component of
      the olfactory cortex. Sensory and intracortical inputs converge on principal
      cells in the anterior piriform cortex (aPC). We characterize organization
      principles of the sensory and intracortical microcircuitry of layer II and III
      principal cells in acute slices of rat aPC using laser-scanning photostimulation
      and fast two-photon population Ca(2+) imaging. Layer II and III principal cells
      are set up on a superficial-to-deep vertical axis. We found that the position on
      this axis correlates with input resistance and bursting behavior. These
      parameters scale with distinct patterns of incorporation into sensory and
      associative microcircuits, resulting in a converse gradient of sensory and
      intracortical inputs. In layer II, sensory circuits dominate superficial cells,
      whereas incorporation in intracortical circuits increases with depth. Layer III
      pyramidal cells receive more intracortical inputs than layer II pyramidal cells,
      but with an asymmetric dorsal offset. This microcircuit organization results in a
      diverse hybrid feedforward/recurrent network of neurons integrating varying
      ratios of intracortical and sensory input depending on a cell's position on the
      superficial-to-deep vertical axis. Since burstiness of spiking correlates with
      both the cell's location on this axis and its incorporation in intracortical
      microcircuitry, the neuronal output mode may encode a given cell's involvement in
      sensory versus associative processing.

PMID- 21865458
TI  - Age-dependent homeostatic plasticity of GABAergic signaling in developing retinal
      networks.
AB  - Developing retinal ganglion cells fire in correlated spontaneous bursts,
      resulting in propagating waves with robust spatiotemporal features preserved
      across development and species. Here we investigate the effects of homeostatic
      adaptation on the circuits controlling retinal waves. Mouse retinal waves were
      recorded in vitro for up to 35 h with a multielectrode array in presence of the
      GABA(A) antagonist bicuculline, allowing us to obtain a precise, time-resolved
      characterization of homeostatic effects in this preparation. Experiments were
      performed at P4-P6, when GABA(A) signaling is depolarizing in ganglion cells, and
      at P7-P10, when GABA(A) signaling is hyperpolarizing. At all ages, bicuculline
      initially increased the wave sizes and other activity metrics. At P5-P6, wave
      sizes decreased toward control levels within a few hours while firing remained
      strong, but this ability to compensate disappeared entirely from P7 onwards. This
      demonstrates that homeostatic control of spontaneous retinal activity maintains
      specific network dynamic properties in an age-dependent manner, and suggests that
      the underlying mechanism is linked to GABA(A) signaling.

PMID- 21865459
TI  - Frequency-dependent tuning of the human motor system induced by transcranial
      oscillatory potentials.
AB  - Different corticothalamic brain modules intrinsically oscillate at a "natural
      frequency" in a topographically organized manner. In "quiescent" human
      sensorimotor regions, the main detectable oscillatory activity peaks at ~20 Hz,
      and partly contributes to determine the state of corticospinal excitability.
      Here, we showed that the transcranial application of an imperceptible, short
      lasting (90 s) electric field oscillating at a physiological range increases
      corticospinal excitability online, with well defined frequency dependence and
      regional specificity. Indeed, the size of motor evoked potentials (MEPs) induced
      by navigated single-pulse TMS over the motor cortex significantly increased only
      during the local application of transcranial alternating current stimulation
      (tACS) at 20 Hz (beta range). Other tACS frequencies (5, 10, and 40 Hz) applied
      on the motor cortex did not impact MEPs' size. Moreover, tACS applied on a
      control site (parietal cortex) and on a peripheral site (ulnar nerve) also failed
      to modulate MEPs. These results help clarifying the functional significance of
      the 20 Hz idling beta rhythm of sensorimotor regions and suggest potential
      clinical applications of this approach.

PMID- 21865460
TI  - Ultrafast population encoding by cortical neurons.
AB  - The processing speed of the brain depends on the ability of neurons to rapidly
      relay input changes. Previous theoretical and experimental studies of the
      timescale of population firing rate responses arrived at controversial
      conclusions, some advocating an ultrafast response scale but others arguing for
      an inherent disadvantage of mean encoded signals for rapid detection of the
      stimulus onset. Here we assessed the timescale of population firing rate
      responses of neocortical neurons in experiments performed in the time domain and
      the frequency domain in vitro and in vivo. We show that populations of
      neocortical neurons can alter their firing rate within 1 ms in response to
      somatically delivered weak current signals presented on a fluctuating background.
      Signals with amplitudes of miniature postsynaptic currents can be robustly and
      rapidly detected in the population firing. We further show that population firing
      rate of neurons of rat visual cortex in vitro and cat visual cortex in vivo can
      reliably encode weak signals varying at frequencies up to ~200-300 Hz, or ~50
      times faster than the firing rate of individual neurons. These results provide
      coherent evidence for the ultrafast, millisecond timescale of cortical population
      responses. Notably, fast responses to weak stimuli are limited to the mean
      encoding. Rapid detection of current variance changes requires extraordinarily
      large signal amplitudes. Our study presents conclusive evidence showing that
      cortical neurons are capable of rapidly relaying subtle mean current signals.
      This provides a vital mechanism for the propagation of rate-coded information
      within and across brain areas.

PMID- 21865461
TI  - Counting ion and water molecules in a streaming file through the open-filter
      structure of the K channel.
AB  - The mechanisms underlying the selective permeation of ions through channel
      molecules are a fundamental issue related to understanding how neurons exert
      their functions. The "knock-on" mechanism, in which multiple ions in the
      selectivity filter are hit by an incoming ion, is one of the leading concepts.
      This mechanism has been supported by crystallographic studies that demonstrated
      ion distribution in the structure of the Streptomyces lividans (KcsA) potassium
      channel. These still pictures under equilibrium conditions, however, do not
      provide a snapshot of the actual, ongoing permeation processes. To understand the
      dynamics of permeation, we determined the ratio of the ion and water flow [the
      water-ion coupling ratio (CR(w-i))] through the KcsA channel by measuring the
      streaming potential (V(stream)) electrophysiologically. The V(stream) value was
      converted to the CR(w-i) value, which reveals how individual ion and water
      molecules are queued in the narrow and short filter during permeation. At high
      K(+) concentrations, the CR(w-i) value was 1.0, indicating that turnover between
      the alternating ion and water arrays occurs in a single-file manner. At low K(+),
      the CR(w-i) value was increased to a point over 2.2, suggesting that the filter
      contained mostly one ion at a time. These average behaviors of permeation were
      kinetically analyzed for a more detailed understanding of the permeation process.
      Here, we envisioned the permeation as queues of ion and water molecules and
      sequential transitions between different patterns of arrays. Under physiological
      conditions, we predicted that the knock-on mechanism may not be predominant.

PMID- 21865462
TI  - Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown
      adipose tissue in spite of systemic leptin resistance.
AB  - Leptin regulates body weight in mice by decreasing appetite and increasing
      sympathetic nerve activity (SNA), which increases energy expenditure in
      interscapular brown adipose tissue (iBAT). Diet-induced obese mice (DIO) are
      resistant to the anorectic actions of leptin. We evaluated whether leptin still
      stimulated sympathetic outflow in DIO mice. We measured iBAT temperature as a
      marker of SNA. We found that obese hyperleptinemic mice have higher iBAT
      temperature than mice on regular diet. Conversely, obese leptin-deficient ob/ob
      mice have lower iBAT temperature. Additionally, leptin increased SNA in obese
      (DIO and ob/ob) and control mice, despite DIO mice being resistant to anorectic
      action of leptin. We demonstrated that neurons in the dorsomedial hypothalamus
      (DMH) of DIO mice mediate the thermogenic responses to hyperleptinemia in obese
      mammals because blockade of leptin receptors in the DMH prevented the thermogenic
      effects of leptin. Peripheral Melotan II (MTII) injection increased iBAT
      temperature, but it was blunted by blockade of DMH melanocortin receptors (MC4Rs)
      by injecting agouti-related peptide (AgRP) directly into the DMH, suggesting a
      physiological role of the DMH on temperature regulation in animals with normal
      body weight. Nevertheless, obese mice without a functional melanocortin system
      (MC4R KO mice) have an increased sympathetic outflow to iBAT compared with their
      littermates, suggesting that higher leptin levels drive sympathoexcitation to
      iBAT by a melanocortin-independent pathway. Because the sympathetic nervous
      system contributes in regulating blood pressure, heart rate, and hepatic glucose
      production, selective leptin resistance may be a crucial mechanism linking
      adiposity and metabolic syndrome.

PMID- 21865463
TI  - Adaptation changes stereoscopic depth selectivity in visual cortex.
AB  - Exposure to specific visual stimuli causes a reduction in sensitivity to similar
      subsequent stimulation. This adaptation effect is observed behaviorally and for
      neurons in the primary visual cortex. Here, we explore the effects of adaptation
      on neurons that encode binocular depth discrimination in the cat's primary visual
      cortex. Our results show that neuronal preference for binocular depth is altered
      selectively with appropriate adaptation. At the preferred depth, adaptation
      causes substantial suppression of subsequent responses. Near the preferred depth,
      the same procedure causes a shift in depth preference. At the null depth,
      adaptation has little effect on binocular depth coding. These results demonstrate
      that prior exposure can change the depth selectivity of binocular neurons. The
      findings are relevant to the theoretical treatment of binocular depth processing.
      Specifically, the prevailing notion of binocular depth encoding based on the
      energy model requires modification.

PMID- 21865464
TI  - MMP2-9 cleavage of dystroglycan alters the size and molecular composition of
      Schwann cell domains.
AB  - Myelinating glial cells exhibit a spectacular cytoarchitecture, because they
      polarize on multiple axes and domains. How this occurs is essentially unknown.
      The dystroglycan-dystrophin complex is required for the function of myelin
      forming Schwann cells. Similar to other tissues, the dystroglycan complex in
      Schwann cells localizes with different dystrophin family members in specific
      domains, thus promoting polarization. We show here that cleavage of dystroglycan
      by matrix metalloproteinases 2 and 9, an event that is considered pathological in
      most tissues, is finely and dynamically regulated in normal nerves and modulates
      dystroglycan complex composition and the size of Schwann cell compartments. In
      contrast, in nerves of Dy(2j/2j) mice, a model of laminin 211 deficiency,
      metalloproteinases 2 and 9 are increased, causing excessive dystroglycan cleavage
      and abnormal compartments. Pharmacological inhibition of cleavage rescues the
      cytoplasmic defects of Dy(2j/2j) Schwann cells. Thus, regulated cleavage may be a
      general mechanism to regulate protein complex composition in physiological
      conditions, whereas unregulated processing is pathogenic and a target for
      treatment in disease.

PMID- 21865465
TI  - Electrical synaptic input to ganglion cells underlies differences in the output
      and absolute sensitivity of parallel retinal circuits.
AB  - Parallel circuits throughout the CNS exhibit distinct sensitivities and responses
      to sensory stimuli. Ambiguities in the source and properties of signals elicited
      by physiological stimuli, however, frequently obscure the mechanisms underlying
      these distinctions. We found that differences in the degree to which activity in
      two classes of Off retinal ganglion cell (RGC) encode information about light
      stimuli near detection threshold were not due to obvious differences in the
      cells' intrinsic properties or the chemical synaptic input the cells received;
      indeed, differences in the cells' light responses were largely insensitive to
      block of fast ionotropic glutamate receptors. Instead, the distinct responses of
      the two types of RGCs likely reflect differences in light-evoked electrical
      synaptic input. These results highlight a surprising strategy by which the retina
      differentially processes and routes visual information and provide new insight
      into the circuits that underlie responses to stimuli near detection threshold.

PMID- 21865466
TI  - Relationship between functional magnetic resonance imaging-identified regions and
      neuronal category selectivity.
AB  - Functional magnetic resonance imaging (fMRI) has been used extensively to
      identify regions in the inferior temporal (IT) cortex that are selective for
      categories of visual stimuli. However, comparatively little is known about the
      neuronal responses relative to these fMRI-defined regions. Here, we compared in
      nonhuman primates the distribution and response properties of IT neurons recorded
      within versus outside fMRI regions selective for four different visual
      categories: faces, body parts, objects, and places. Although individual neurons
      that preferred each of the four categories were found throughout the sampled
      regions, they were most concentrated within the corresponding fMRI region,
      decreasing significantly within 1-4 mm from the edge of these regions.
      Furthermore, the correspondence between fMRI and neuronal distributions was
      specific to neurons that increased their firing rates in response to the visual
      stimuli but not to neurons suppressed by visual stimuli, suggesting that the
      processes associated with inhibiting neuronal activity did not contribute
      strongly to the fMRI signal in this experiment.

PMID- 21865467
TI  - Polycystin-1 is required for stereocilia structure but not for
      mechanotransduction in inner ear hair cells.
AB  - The polycystic kidney disease-1 (Pkd1) gene encodes a large transmembrane protein
      (polycystin-1, or PC-1) that is reported to function as a fluid flow sensor in
      the kidney. As a member of the transient receptor potential family, PC-1 has also
      been hypothesized to play a role in the elusive mechanoelectrical transduction
      (MET) channel in inner ear hair cells. Here, we analyze two independent mouse
      models of PC-1, a knock-in (KI) mutant line and a hair cell-specific inducible
      Cre-mediated knock-out line. Both models exhibit normal MET channel function at
      neonatal ages despite hearing loss and ultrastructural abnormalities of
      sterecilia that remain properly polarized at adult ages. These findings
      demonstrate that PC-1 plays an essential role in stereocilia structure and
      maintenance but not directly in MET channel function or planar cell polarity. We
      also demonstrate that PC-1 is colocalized with F-actin in hair cell stereocilia
      in vivo, using a hemagglutinin-tagged PC-1 KI mouse model, and in renal
      epithelial cell microvilli in vitro. These results not only demonstrate a novel
      role for PC-1 in the cochlea, but also suggest insight into the development of
      polycystic kidney disease.

PMID- 21865468
TI  - Acute cocaine exposure weakens GABA(B) receptor-dependent G-protein-gated
      inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental
      area.
AB  - Enhanced glutamatergic neurotransmission in dopamine (DA) neurons of the ventral
      tegmental area (VTA), triggered by a single cocaine injection, represents an
      early adaptation linked to the more enduring effects of abused drugs that
      characterize addiction. Here, we examined the impact of in vivo cocaine exposure
      on metabotropic inhibitory signaling involving G-protein-gated inwardly
      rectifying K(+) (Girk) channels in VTA DA neurons. Somatodendritic Girk currents
      evoked by the GABA(B) receptor (GABA(B)R) agonist baclofen were diminished in a
      dose-dependent manner in mice given a single cocaine injection. This adaptation
      persisted for 3-4 d, was specific for DA neurons of the VTA, and occurred in
      parallel with an increase in spontaneous glutamatergic neurotransmission. No
      additional suppression of GABA(B)R-Girk signaling was observed following repeated
      cocaine administration. While total Girk2 and GABA(B)R1 mRNA and protein levels
      were unaltered by cocaine exposure in VTA DA neurons, the cocaine-induced
      decrease in GABA(B)R-Girk signaling correlated with a reduction in Girk2
      containing channels at the plasma membrane in VTA DA neurons. Systemic
      pretreatment with sulpiride, but not SCH23390 (7-chloro-3-methyl-1-phenyl-1,2,4,5
      tetrahydro-3-benzazepin-8-ol), prevented the cocaine-induced suppression of
      GABA(B)R-Girk signaling, implicating D(2/3) DA receptor activation in this
      adaptation. The acute cocaine-induced weakening of somatodendritic Girk signaling
      complements the previously demonstrated cocaine-induced strengthening of
      glutamatergic neurotransmission, likely contributing to enhanced output of VTA DA
      neurons during the early stages of addiction.

PMID- 21865469
TI  - Hippocampal telomerase is involved in the modulation of depressive behaviors.
AB  - Telomere and telomerase alterations have been reported in mood disorders.
      However, the role of telomerase in depression remains unclear. Here we show that
      chronic mild stress (CMS) led to a significant decrease in telomerase reverse
      transcriptase (TERT) level and telomerase activity in the hippocampus. Treatment
      with antidepressant fluoxetine reversed the CMS-induced TERT and telomerase
      activity changes. Inhibiting telomerase by systemic administration (100 mg . kg(
      1) . d(-1), i.p., for 14 d), intrahippocampal microinjection (0.7 MUmol, 2 MUl),
      or infusion (using an osmotic minipump, 0.134 MUg/MUl, 0.25 MUl/h) of 3'-azido
      deoxythymidine (AZT) resulted in depression-like behaviors and impaired
      hippocampal neurogenesis in mice. In contrast, overexpressing telomerase by
      intrahippocampal infusion of recombinant adenovirus vector expressing mouse TERT
      (Ad-mTERT-GFP) led to neurogenesis upregulation, produced antidepressant-like
      behaviors, and prevented the CMS-induced behavioral modifications. Disrupting
      neurogenesis in the dentate gyrus by X-irradiation (15 Gy) of a restricted region
      of mouse brain containing the hippocampus abolished the antidepressant-like
      effect of Ad-mTERT-GFP. Additionally, AZT had no effect on DNA polymerase
      activity and did not cause cell damage in vitro and in vivo. Microinjection of
      AZT into the subventricular zone of lateral ventricle (0.7 MUmol, 2 MUl)
      inhibited local neurogenesis but had no behavioral effect. These results suggest
      that hippocampal telomerase is involved in the modulation of depression-related
      behaviors, possibly by regulating adult neurogenesis.

PMID- 21865471
TI  - A model of intracellular theta phase precession dependent on intrinsic
      subthreshold membrane currents.
AB  - A hippocampal place cell fires at an increasingly earlier phase in relation to
      the extracellular theta rhythm as a rodent moves through the place field. The
      present report presents a compartment model of a CA1 pyramidal cell that explains
      the increase in amplitude and the phase precession of intracellular theta
      oscillations, with the assumption that the cell receives an asymmetric ramp
      depolarization (<10 mV) in the place field and rhythmic inhibitory and/or
      excitatory synaptic driving. Intracellular subthreshold membrane potential
      oscillations (MPOs) increase in amplitude and frequency, and show phase
      precession within the place field. Theta phase precession and MPO power and
      frequency increase in the place field are caused by a shift in excitatory
      inhibitory response, intrinsic theta-frequency resonance, and intrinsic
      oscillations that depend on voltage-dependent persistent Na(+) and slowly
      inactivating K(+) currents, but not on I(h). Phase precession is diminished when
      theta-frequency resonance is decreased. Simulated spikes fire near the peak of
      MPOs and precess similarly as the MPOs. The phase of the MPOs/spikes codes for
      distance in a one-dimensional place field, and phase precession is only weakly
      dependent on firing rate, running speed, or the duration needed to cross the
      place field. In addition, phase precession within the place field resumes quickly
      after disruption by maximal afferent pulse stimulation.

PMID- 21865470
TI  - Memory-guided learning: CA1 and CA3 neuronal ensembles differentially encode the
      commonalities and differences between situations.
AB  - Memory influences learning, but how neural signals support such transfer are
      unknown. To investigate these mechanisms, we trained rats to perform a standard
      spatial memory task in a plus maze and tested how training affected learning and
      neural coding in two new task variants. A switch task exchanged the start and
      goal locations in the same environment, whereas, an altered environment task
      contained unfamiliar local and distal cues. Learning was facilitated in both
      variants compared with the acquisition of the standard task. In the switch task,
      performance was largely maintained, and was accompanied by immediate and stable
      place-field remapping. Place-field maps in CA1 were anticorrelated in the
      standard and switch sessions, and the anticorrelation covaried with switch
      performance. Simultaneously, CA3 maps were uncorrelated overall in the standard
      and switch, though many CA3 cells had fields in shifted locations in the same
      maze arms. In the altered environment, performance was initially impaired, and
      place fields changed dynamically. CA1 fields were initially unstable, and their
      stabilization correlated with improving performance. Most CA3 cells, however,
      stopped firing on the maze in the altered environment, even as the same cells
      maintained prominent fields in standard sessions recorded before and after. CA1
      and CA3 place fields thus revealed different coding dynamics that correlated with
      both learning and memory performance. Together, CA1 and CA3 ensembles represented
      the similarities and differences between new and familiar situations through
      concurrent rate and place remapping.

PMID- 21865472
TI  - Single synapse information coding in intraburst spike patterns of central pattern
      generator motor neurons.
AB  - Burst firing is ubiquitous in nervous systems and has been intensively studied in
      central pattern generators (CPGs). Previous works have described subtle
      intraburst spike patterns (IBSPs) that, despite being traditionally neglected for
      their lack of relation to CPG motor function, were shown to be cell-type specific
      and sensitive to CPG connectivity. Here we address this matter by investigating
      how a bursting motor neuron expresses information about other neurons in the
      network. We performed experiments on the crustacean stomatogastric pyloric CPG,
      both in control conditions and interacting in real-time with computer model
      neurons. The sensitivity of postsynaptic to presynaptic IBSPs was inferred by
      computing their average mutual information along each neuron burst. We found that
      details of input patterns are nonlinearly and inhomogeneously coded through a
      single synapse into the fine IBSPs structure of the postsynaptic neuron following
      burst. In this way, motor neurons are able to use different time scales to convey
      two types of information simultaneously: muscle contraction (related to bursting
      rhythm) and the behavior of other CPG neurons (at a much shorter timescale by
      using IBSPs as information carriers). Moreover, the analysis revealed that the
      coding mechanism described takes part in a previously unsuspected information
      pathway from a CPG motor neuron to a nerve that projects to sensory brain areas,
      thus providing evidence of the general physiological role of information coding
      through IBSPs in the regulation of neuronal firing patterns in remote circuits by
      the CNS.

PMID- 21865473
TI  - Functional heterogeneity of macaque lateral intraparietal neurons.
AB  - The macaque lateral intraparietal area (LIP) has been implicated in many
      cognitive processes, ranging from saccade planning and spatial attention to
      timing and categorization. Importantly, different research groups have used
      different criteria for including LIP neurons in their studies. While some
      research groups have selected LIP neurons based on the presence of memory-delay
      activity, other research groups have used other criteria such as visual,
      presaccadic, and/or memory activity. We recorded from LIP neurons that were
      selected based on spatially selective saccadic activity but regardless of memory
      delay activity in macaque monkeys. To test anticipatory climbing activity, we
      used a delayed visually guided saccade task with a unimodal schedule of go-times,
      for which the conditional probability that the go-signal will occur rises
      monotonically as a function of time. A subpopulation of LIP neurons showed
      anticipatory activity that mimicked the subjective hazard rate of the go-signal
      when the animal was planning a saccade toward the receptive field. A large
      subgroup of LIP neurons, however, did not modulate their firing rates according
      to the subjective hazard function. These non-anticipatory neurons were strongly
      influenced by salient visual stimuli appearing in their receptive field, but less
      so by the direction of the impending saccade. Thus, LIP contains a heterogeneous
      population of neurons related to saccade planning or visual salience, and these
      neurons are spatially intermixed. Our results suggest that between-study
      differences in neuronal selection may have contributed significantly to the
      findings of different research groups with respect to the functional role of area
      LIP.

PMID- 21865474
TI  - Endogenous brain-derived neurotrophic factor in the nucleus tractus solitarius
      tonically regulates synaptic and autonomic function.
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly
      expressed in the nucleus tractus solitarius (nTS), the principal target of
      cardiovascular primary afferent input to the brainstem. However, little is known
      about the role of BDNF signaling in nTS in cardiovascular homeostasis. We
      examined whether BDNF in nTS modulates cardiovascular function in vivo and
      regulates synaptic and/or neuronal activity in isolated brainstem slices.
      Microinjection of BDNF into the rat medial nTS (mnTS), a region critical for
      baroreflex control of sympathetic outflow, produced dose-dependent increases in
      mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve
      activity (LSNA) that were blocked by the tyrosine kinase inhibitor K252a. In
      contrast, immunoneutralization of endogenous BDNF (anti-BDNF), or microinjection
      of K252a alone, decreased MAP, HR, and LSNA. The effects of anti-BDNF were
      abolished by blockade of ionotropic glutamate receptors, indicating a role for
      glutamate signaling in the response to BDNF. In vitro, BDNF reduced the amplitude
      of miniature EPSCs as well as solitary tract (TS) evoked EPSC amplitude and
      action potential discharge (APD) in second-order nTS neurons. BDNF effects on
      EPSCs were independent of GABAergic signaling and abolished by AMPA receptor
      blockade. In contrast, K252a increased spontaneous EPSC frequency and TS evoked
      EPSC amplitude. BDNF also attenuated APD evoked by injection of depolarizing
      current into second-order neurons, indicating reduced intrinsic neuronal
      excitability. Our data demonstrate that BDNF signaling in mnTS plays a tonic role
      in regulating cardiovascular function, likely via modulation of primary afferent
      glutamatergic excitatory transmission and neural activity.

PMID- 21865475
TI  - Antipsychotic drugs rapidly induce dopamine neuron depolarization block in a
      developmental rat model of schizophrenia.
AB  - Repeated administration of antipsychotic drugs to normal rats has been shown to
      induce a state of dopamine neuron inactivation known as depolarization block,
      which correlates with the ability of the drugs to exhibit antipsychotic efficacy
      and extrapyramidal side effects in schizophrenia patients. Nonetheless, in normal
      rats depolarization block requires weeks of antipsychotic drug administration,
      whereas schizophrenia patients exhibit initial effects soon after initiating
      antipsychotic drug treatment. We now report that, in a developmental disruption
      rat model of schizophrenia [methyl-azoxymethanol acetate (20 mg/kg, i.p.)
      injected into G17 pregnant female rats, with offspring tested as adults], the
      extant hyperdopaminergic state combines with the excitatory actions of a first-
      (haloperidol; 0.6 mg/kg, i.p.) and a second- (sertindole; 2.5 mg/kg, i.p.)
      generation antipsychotic drug to rapidly induce depolarization block in ventral
      tegmental area dopamine neurons. Acute injection of either antipsychotic drug
      induced an immediate reduction in the number of spontaneously active dopamine
      neurons (cells per electrode track; termed population activity). Repeated
      administration of either antipsychotic drug for 1, 3, 7, 15, and 21 d continued
      to reduce dopamine neuron population activity. Both acute and repeated effects on
      population activity were reversed by acute apomorphine injections, which is
      consistent with the reversal of dopamine neuron depolarization block. Although
      this action may account for the effects of D2 antagonist drugs on alleviating
      psychosis and the lack of development of tolerance in humans, the drugs appear to
      do so by inducing an offsetting deficit rather than attacking the primary
      pathology present in schizophrenia.

PMID- 21865477
TI  - Anatomical evidence for the involvement of the macaque ventrolateral prefrontal
      area 12r in controlling goal-directed actions.
AB  - The macaque ventrolateral prefrontal (VLPF) area 12r is thought to be involved in
      higher-order nonspatial information processing. We found that this area is
      connectionally heterogeneous, and the intermediate part is fully integrated in a
      cortical network involved in selecting and controlling object-oriented hand and
      mouth actions. Specifically, intermediate area 12r displayed dense connections
      with the caudal half of area 46v and orbitofrontal areas and relatively strong
      extraprefrontal connections involving the following: (1) the hand- and mouth
      related ventral premotor area F5 and the anterior intraparietal (AIP) area,
      jointly involved in visuomotor transformations for grasping; (2) the SII sector
      that is connected to AIP and F5; (3) a sector of the inferotemporal area TEa/m,
      primarily corresponding to the sector densely connected to AIP; and (4) the
      insular and opercular frontal sectors, which are connected to AIP and F5. This
      connectivity pattern differed markedly from those of the caudal and rostral parts
      of area 12r. Caudal area 12r displayed dense connections with the caudal part of
      the VLPF, including oculomotor areas 8/FEF and 45B, relatively weak orbitofrontal
      connections and extraprefrontal connections limited to the inferotemporal cortex.
      Rostral area 12r displayed connections mostly with rostral prefrontal and
      orbitofrontal areas and relatively weaker connections with the fundus and the
      upper bank of the superior temporal sulcus. The present data suggest that the
      intermediate part of area 12r is involved in nonspatial information processing
      related to object properties and identity, for selecting and controlling goal
      directed hand and mouth actions.

PMID- 21865476
TI  - Orientation selectivity of synaptic input to neurons in mouse and cat primary
      visual cortex.
AB  - Primary visual cortex (V1) is the site at which orientation selectivity emerges
      in mammals: visual thalamus afferents to V1 respond equally to all stimulus
      orientations, whereas their target V1 neurons respond selectively to stimulus
      orientation. The emergence of orientation selectivity in V1 has long served as a
      model for investigating cortical computation. Recent evidence for orientation
      selectivity in mouse V1 opens cortical computation to dissection by genetic and
      imaging tools, but also raises two essential questions: (1) How does orientation
      selectivity in mouse V1 neurons compare with that in previously described
      species? (2) What is the synaptic basis for orientation selectivity in mouse V1?
      A comparison of orientation selectivity in mouse and in cat, where such measures
      have traditionally been made, reveals that orientation selectivity in mouse V1 is
      weaker than in cat V1, but that spike threshold plays a similar role in narrowing
      selectivity between membrane potential and spike rate. To uncover the synaptic
      basis for orientation selectivity, we made whole-cell recordings in vivo from
      mouse V1 neurons, comparing neuronal input selectivity-based on membrane
      potential, synaptic excitation, and synaptic inhibition-to output selectivity
      based on spiking. We found that a neuron's excitatory and inhibitory inputs are
      selective for the same stimulus orientations as is its membrane potential
      response, and that inhibitory selectivity is not broader than excitatory
      selectivity. Inhibition has different dynamics than excitation, adapting more
      rapidly. In neurons with temporally modulated responses, the timing of excitation
      and inhibition was different in mice and cats.

PMID- 21865478
TI  - Sex differences in the use of anticipatory brain activity to encode emotional
      events.
AB  - Women and men differ in the way they experience emotional events. Previous work
      has indicated that the impact of an emotional event depends on how it is
      anticipated. Separately, it has been shown that anticipation affects memory
      formation. Here, we assessed whether anticipatory brain activity influences the
      encoding of emotional events into long-term memory and, in addition, how
      biological sex affects the use of such activity. Electrical brain activity was
      recorded from the scalps of healthy men and women while they performed an
      incidental encoding task (indoor/outdoor judgments) on pleasant, unpleasant, and
      neutral pictures. Pictures were preceded by a cue that indicated the valence of
      the upcoming item. Memory was tested after a 20 min delay with a recognition task
      incorporating the remember/know procedure. Brain activity before picture onset
      predicted later memory of an event. Crucially, the role of anticipatory activity
      depended entirely on the valence of a picture and the sex of an individual. Right
      lateralized anticipatory activity selectively influenced the encoding of
      unpleasant pictures in women, but not in men. These findings indicate that
      anticipatory processes influence the way in which women encode negative events
      into memory. The selective use of such activity may indicate that anticipatory
      activity is one mechanism by which individuals regulate their emotions.

PMID- 21865480
TI  - The representation of visual and motor aspects of reaching movements in the human
      motor cortex.
AB  - The human primary motor cortex (M1) is robustly activated during visually guided
      hand movements. M1 multivoxel patterns of functional MRI activation are more
      correlated during repeated hand movements to the same targets than to greatly
      differing ones, and therefore potentially contain information about movement
      direction. It is unclear, however, whether direction specificity is due to the
      motor command, as implicitly assumed, or to the visual aspects of the task, such
      as the target location and the direction of the cursor's trajectory. To
      disambiguate the visual and motor components, different visual-to-motor
      transformations were applied during an fMRI scan, in which participants made
      visually guided hand movements in various directions. The first run was the
      "baseline" (i.e., visual and motor mappings were matched); in the second run
      ("rotation"), the cursor movement was rotated by 45 degrees  with respect to the
      joystick movement. As expected, positive correlations were seen between the M1
      multivoxel patterns evoked by the baseline run and by the rotation run, when the
      two movements were matched in their movement direction but the visual aspects
      differed. Importantly, similar correlations were observed when the visual
      elements were matched but the direction of hand movement differed. This indicates
      that M1 is sensitive to both motor and visual components of the task. However,
      repeated observation of the cursor movement without concurrent joystick control
      did not elicit significant activation in M1 or any correlated patterns of
      activation. Thus, visual aspects of movement are encoded in M1 only when they are
      coupled with motor consequences.

PMID- 21865479
TI  - Two amino acid residues contribute to a cation-pi binding interaction in the
      binding site of an insect GABA receptor.
AB  - Cys-loop receptor binding sites characteristically possess an "aromatic box,"
      where several aromatic amino acid residues surround the bound ligand. A cation-pi
      interaction between one of these residues and the natural agonist is common,
      although the residue type and location are not conserved. Even in the closely
      related vertebrate GABA(A) and GABA(C) receptors, residues in distinct locations
      perform this role: in GABA(A) receptors, a Tyr residue in loop A forms a cation
      pi interaction with GABA, while in GABA(C) receptors it is a loop B residue. GABA
      activated Cys-loop receptors also exist in invertebrates, where they have
      distinct pharmacologies and are the target of a range of pesticides. Here we
      examine the location of GABA in an insect binding site by incorporating a series
      of fluorinated Phe derivatives into the receptor binding pocket using unnatural
      amino acid mutagenesis, and evaluating the resulting receptors when expressed in
      Xenopus oocytes. A homology model suggests that two aromatic residues (in loops B
      and C) are positioned such that they could contribute to a cation-pi interaction
      with the primary ammonium of GABA, and the data reveal a clear correlation
      between the GABA EC(50) and the cation-pi binding ability both at Phe206 (loop B)
      and Tyr254 (loop C), demonstrating for the first time the contribution of two
      aromatic residues to a cation-pi interaction in a Cys-loop receptor.

PMID- 21865481
TI  - Reflections on the evolution of cardiac biomarkers.

PMID- 21865482
TI  - Serum concentrations of insulin-like growth factor (IGF)-1 and IGF binding
      protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio, and markers of bone turnover: reference
      values for French children and adolescents and z-score comparability with other
      references.
AB  - BACKGROUND: A reference model for converting serum growth factor and bone
      metabolism markers into an SD score (SDS) is required for clinical practice. We
      aimed to establish reference values of serum insulin-like growth factor-1 (IGF-1)
      and IGF binding protein 3 (IGFBP-3) concentrations and bone metabolism markers in
      French children, to generate a model for converting values into SDS for age, sex,
      and pubertal stage. METHODS: We carried out a cross-sectional study of 1119
      healthy white children ages 6-20 years. We assessed concentrations of serum IGF
      1, IGFBP-3, carboxyterminal telopeptide alpha1 chain of type I collagen
      (CrossLaps), and bone alkaline phosphatase concentrations and height, weight, and
      pubertal stage, and used semiparametric regression to develop a model. RESULTS: A
      single regression model to calculate the SDSs with an online calculator was
      provided. A positive relationship was found between SDS for serum IGF-1 and IGFBP
      3, IGF/IGFBP-3 mol/L ratio, and anthropometric parameters (P < 0.0001), with
      slightly greater effects observed for height than for body mass index (BMI).
      There was a negative relationship between serum CrossLaps concentration and BMI,
      and a positive relationship between serum CrossLaps concentration and height. A
      comparison of serum IGF-1 reference databases for children showed marked
      variation as a function of age and pubertal group; smooth changes with age and
      puberty were observed only in our model. CONCLUSIONS: This new model for the
      assessment of SDS reference values specific for age, sex, and pubertal stage may
      help to increase the diagnostic power of these parameters for the assessment of
      growth and bone metabolism disorders. This study also provides information about
      the physiological role of height and BMI for the interpretation of these
      parameters.

PMID- 21865483
TI  - Reference values for aldosterone-renin ratios in normotensive individuals and
      effect of changes in dietary sodium consumption.
AB  - BACKGROUND: Determination of the aldosterone-to-renin ratio (ARR) in blood is the
      preferred screening test for primary aldosteronism. Renin can be measured as the
      plasma renin activity (PRA) or the plasma renin concentration (PRC).
      Consequently, the ARR can be measured either based on the PRA (ARR(pra)) or based
      on the PRC (ARR(prc)). In contrast with the ARR(pra), the data on reference
      values for the ARR(prc) are limited. Moreover, whether the ARR(pra) or ARR(prc)
      is affected by variations in salt intake is unknown. METHODS: We measured the
      PRA, the PRC, and serum aldosterone in 100 normotensive individuals between 20
      and 70 years of age before and after a 3-day oral sodium-loading test (SLT).
      Participants were stratified according to age and sex. Data are presented as the
      median and interquartile range (IQR). RESULTS: Urinary sodium excretion after the
      SLT was >=200 mmol/24 h in all participants. Serum aldosterone, PRA, and PRC
      values were significantly reduced after the SLT. PRC and PRA results were highly
      correlated [Spearman rank correlation r(s) = 0.80 and 0.74 before and after SLT,
      respectively; P < 0.001 for both]. The central 95% reference intervals for
      ARR(pra) before and after SLT were 0.07-1.45 h(-1) and 0.06-1.84 h(-1),
      respectively. The corresponding reference intervals for ARR(prc) were 4.1-81.3
      pmol/ng and 3.9-74.8 pmol/ng. The median ARR(prc) decreased after the SLT from
      19.5 pmol/ng (IQR, 13.0-29.4 pmol/ng) to 18.6 pmol/ng (IQR, 9.4-27.1 pmol/ng) (P
      = 0.005), whereas the median ARR(pra) did not change (P = 0.12). Both the
      ARR(prc) and ARR(pra) at baseline were higher in women than in men, whereas no
      sex difference was observed after sodium loading. CONCLUSIONS: We present
      reference values for the ARR(prc) for healthy individuals. The ARR is affected to
      a variable degree by sex and sodium intake.

PMID- 21865484
TI  - Newborn screening for metabolic disorders: how are we doing, and where are we
      going?

PMID- 21865485
TI  - An interview with Dr. Eugene Braunwald. Interview by Misia Landau.

PMID- 21865486
TI  - What are the main research findings during the last 5 years that have changed my
      approach to clinical practice?
AB  - When asked to address the above question, findings that appeared to be among the
      most relevant included (1) interventions in the delivery room directed at
      supporting the physiological transition from intrauterine to extrauterine life
      rather than actively intervening in it; (2) recent data suggesting that keeping
      extremely low-gestational age neonates at a pulse oximeter saturation (SpO(2)) of
      91-95% would increase their chances of survival compared with aiming for lower
      SpO(2) values; (3) using caffeine citrate in infants <1250 g with apnoea of
      prematurity improves neurodevelopmental outcome; (4) injecting antivascular
      epithelial growth factor into the vitreous seems to be an effective treatment for
      retinopathy of prematurity and (5) moderate hypothermia for perinatal hypoxic
      ischaemic encephalopathy increases the likelihood of survival without
      neurological impairment. Here, data that support these recent changes in approach
      will be presented and discussed.

PMID- 21865487
TI  - Born just a few weeks early: does it matter?
AB  - Until recently, infants born at moderate preterm (32-33 weeks) and late preterm
      (34-36 weeks) gestations have gone largely unstudied. Since their outcomes were
      thought to be similar to those of infants born at 37 weeks and above, they have
      historically been managed in much the same way as infants born at term. However,
      accumulating data indicate that risks of morbidity and mortality are
      significantly greater in this group than previously believed. Since moderate and
      late preterm infants account for around 6% of all births, very large numbers of
      babies are potentially affected. Although their problems may be less obvious than
      those of extremely preterm infants, the population impact of long-term health and
      neurodevelopmental problems in this group will be substantial. This review
      summarises the current available literature, highlights gaps in knowledge and
      discusses the implications of late preterm birth for both clinical practice and
      research in the perinatal period and beyond.

PMID- 21865490
TI  - Hurricane Katrina's first responders: the struggle to protect and serve in the
      aftermath of the disaster.
AB  - OBJECTIVE: Hurricane Katrina highlighted both the crucial role of first
      responders in times of disaster and the resultant stress on them and their
      families. The primary objective of this study was to describe the mental health
      status and symptoms of first responders in the New Orleans area. We further
      hypothesized that given the extent of the disaster and slowness of recovery,
      symptoms of posttraumatic stress and depression would not decrease after the
      first-year anniversary of Hurricane Katrina. METHODS: A total of 1382 first
      responders, including respondents from police, fire, emergency medical services,
      and city workers, participated in this longitudinal study. The first screening
      was conducted between 6 and 9 months after Hurricane Katrina and the second round
      of data collection was conducted 13 to 18 months after the hurricane. A subsample
      of the respondents (n = 87) were matched at both time points, which allowed for
      paired sample comparisons. We measured all of the respondents' levels of
      traumatic experiences, alcohol use, partner conflict, requests for services,
      posttraumatic stress, and depression. RESULTS: More than one-quarter of the first
      responders reported the following traumatic experiences: witnessed injury or
      death (70%); damage to home (93%); injury to a friend (25%); and previous loss or
      trauma (30%). Data also revealed that at least 10% of the respondents had
      significant levels of posttraumatic stress symptoms; 25% of the participants
      reported significant levels of depression; and more than 40% reported increased
      alcohol use and conflict with partner (41%). A statistically significant decrease
      in the symptoms of posttraumatic stress or depression was not found within 18
      months of Hurricane Katrina. CONCLUSIONS: Results suggest that the severity of
      the traumas experienced from both the impact of Hurricane Katrina and the
      subsequent recovery has important mental health implications for first
      responders. Reports of symptoms of anxiety or depression should be attended to so
      as to prevent increasing symptoms that could negatively affect the first
      responder and his or her family. These findings highlight the importance of not
      only providing mental health services for first responders but also having
      adequate plans in place before natural or technological disasters strike.

PMID- 21865488
TI  - Biosynthesis of the major tetrahydroxystilbenes in spruce, astringin and
      isorhapontin, proceeds via resveratrol and is enhanced by fungal infection.
AB  - Stilbenes are dibenzyl polyphenolic compounds produced in several unrelated plant
      families that appear to protect against various biotic and abiotic stresses.
      Stilbene biosynthesis has been well described in economically important plants,
      such as grape (Vitis vinifera), peanut (Arachis hypogaea), and pine (Pinus
      species). However, very little is known about the biosynthesis and ecological
      role of stilbenes in spruce (Picea), an important gymnosperm tree genus in
      temperate and boreal forests. To investigate the biosynthesis of stilbenes in
      spruce, we identified two similar stilbene synthase (STS) genes in Norway spruce
      (Picea abies), PaSTS1 and PaSTS2, which had orthologs with high sequence identity
      in sitka (Picea sitchensis) and white (Picea glauca) spruce. Despite the
      conservation of STS sequences in these three spruce species, they differed
      substantially from angiosperm STSs. Several types of in vitro and in vivo assays
      revealed that the P. abies STSs catalyze the condensation of p-coumaroyl-coenzyme
      A and three molecules of malonyl-coenzyme A to yield the trihydroxystilbene
      resveratrol but do not directly form the dominant spruce stilbenes, which are
      tetrahydroxylated. However, in transgenic Norway spruce overexpressing PaSTS1,
      significantly higher amounts of the tetrahydroxystilbene glycosides, astringin
      and isorhapontin, were produced. This result suggests that the first step of
      stilbene biosynthesis in spruce is the formation of resveratrol, which is further
      modified by hydroxylation, O-methylation, and O-glucosylation to yield astringin
      and isorhapontin. Inoculating spruce with fungal mycelium increased STS
      transcript abundance and tetrahydroxystilbene glycoside production. Extracts from
      STS-overexpressing lines significantly inhibited fungal growth in vitro compared
      with extracts from control lines, suggesting that spruce stilbenes have a role in
      antifungal defense.

PMID- 21865489
TI  - Antisense suppression of the small chloroplast protein CP12 in tobacco alters
      carbon partitioning and severely restricts growth.
AB  - The thioredoxin-regulated chloroplast protein CP12 forms a multienzyme complex
      with the Calvin-Benson cycle enzymes phosphoribulokinase (PRK) and glyceraldehyde
      3-phosphate dehydrogenase (GAPDH). PRK and GAPDH are inactivated when present in
      this complex, a process shown in vitro to be dependent upon oxidized CP12. The
      importance of CP12 in vivo in higher plants, however, has not been investigated.
      Here, antisense suppression of CP12 in tobacco (Nicotiana tabacum) was observed
      to impact on NAD-induced PRK and GAPDH complex formation but had little effect on
      enzyme activity. Additionally, only minor changes in photosynthetic carbon
      fixation were observed. Despite this, antisense plants displayed changes in
      growth rates and morphology, including dwarfism and reduced apical dominance. The
      hypothesis that CP12 is essential to separate oxidative pentose phosphate pathway
      activity from Calvin-Benson cycle activity, as proposed in cyanobacteria, was
      tested. No evidence was found to support this role in tobacco. Evidence was seen,
      however, for a restriction to malate valve capacity, with decreases in NADP
      malate dehydrogenase activity (but not protein levels) and pyridine nucleotide
      content. Antisense repression of CP12 also led to significant changes in carbon
      partitioning, with increased carbon allocation to the cell wall and the organic
      acids malate and fumarate and decreased allocation to starch and soluble
      carbohydrates. Severe decreases were also seen in 2-oxoglutarate content, a key
      indicator of cellular carbon sufficiency. The data presented here indicate that
      in tobacco, CP12 has a role in redox-mediated regulation of carbon partitioning
      from the chloroplast and provides strong in vivo evidence that CP12 is required
      for normal growth and development in plants.

PMID- 21865491
TI  - What rules of thumb do clinicians use to decide whether to antagonize
      nondepolarizing neuromuscular blocking drugs?
AB  - BACKGROUND: In anesthesia practice, inadequate antagonism of neuromuscular
      blocking drugs (NMBD) may lead to frequent prevalence of residual neuromuscular
      block that is associated with morbidity and death. In this study we analyzed the
      clinical decision on antagonizing NMBD to generate hypotheses about barriers to
      the introduction of experts' recommendations into clinical practice. METHODS:
      Sequential surveys were conducted among 108 clinical anesthesiologists to elicit
      the rules of thumb (heuristics) that support their decisions and provide a
      measurement of the confidence the clinicians have in their own decisions in
      comparison with their peers' decisions. RESULTS: The 2 most frequently used
      heuristics for administering reversal were "the interval since the last NMBD dose
      was short" and "the breathing pattern is inadequate," chosen by 73% and 71% of
      the clinicians, respectively. Clinicians considered that the prevalence of
      clinically significant residual block is higher in their colleagues' practices
      than in their own practice (60% vs 16%, odds ratio=7.8, 95% confidence interval,
      3.8 to 16.2, P=0.0001). The clinicians were less likely to use antagonists if >60
      minutes had elapsed after a single dose of atracurium (0.5 mg/kg) (31%) in
      comparison with after rocuronium 0.6 mg/kg (53%) (P=0.0035). CONCLUSIONS: In our
      institution, the clinical decision to antagonize NMBD is mainly based on the
      pharmacological forecast and a qualitative judgment of the adequacy of the
      breathing pattern. Clinicians judge themselves as better skilled at avoiding
      residual block than they do their colleagues, making them overconfident in their
      capacity to estimate the duration of action of intermediate-acting NMBD.
      Awareness of these systematic errors related to clinical intuition may facilitate
      the adoption of experts' recommendations into clinical practice.

PMID- 21865492
TI  - The etomidate requirement is decreased in patients with obstructive jaundice.
AB  - BACKGROUND: Patients with obstructive jaundice have increased sensitivity to
      inhaled anesthetics. In rodent brain, bilirubin can enhance gamma-aminobutyric
      acid A/glycinergic synaptic transmission. Etomidate is a nonbarbiturate hypnotic
      that induces sedation through gamma-aminobutyric acid A receptors in the central
      nervous system. We tested the hypothesis that patients with obstructive jaundice
      have an altered sensitivity to etomidate. METHODS: The study design was a
      comparison of etomidate requirements to reach a Bispectral Index of 50 in
      patients with obstructive jaundice versus patients with chronic cholelithiasis
      and normal bilirubin levels. Etomidate was infused at 30 MUg/kg/min until this
      end point was reached. RESULTS: The etomidate requirement in the obstructive
      jaundice group was lower than that in the control group (150+/-46 MUg/kg vs 206+/
      74 MUg/kg, P=0.007). The average decrease in etomidate requirement was 56 MUg/kg
      (95% confidence interval: 16-96 MUg/kg). In addition, we found a significant
      negative correlation between serum total bilirubin and etomidate requirement with
      Pearson r of -0.545, and 95% confidence interval for r value (-0.791 to -0.148).
      All subjects were hemodynamically stable during the study. CONCLUSIONS: Etomidate
      requirements to reach a level of anesthesia defined by a Bispectral Index of 50
      are reduced in patients with obstructive jaundice.

PMID- 21865493
TI  - Intrathecal ultra-low dose naloxone enhances the antinociceptive effect of
      morphine by enhancing the reuptake of excitatory amino acids from the synaptic
      cleft in the spinal cord of partial sciatic nerve-transected rats.
AB  - BACKGROUND: In this study, we examined the effects of ultra-low dose naloxone on
      the antinociceptive effect of morphine and on spinal cord dorsal horn glutamate
      transporter expression in rats with neuropathic pain. METHODS: Neuropathic pain
      was induced in male Wistar rats by partial transection of the left sciatic nerve
      and an intrathecal catheter was implanted for drug administration; in some rats,
      an intrathecal microdialysis probe for cerebrospinal fluid (CSF) dialysate
      collection was also implanted. Nociception was assessed using the plantar test, a
      Hargreaves radiant heat apparatus, and by the von Frey test, using a dynamic
      plantar anesthesiometer. Glutamate transporter protein expression in the left
      spinal cord dorsal horn was examined by Western blotting and
      immunohistochemistry. Levels of the excitatory amino acids (EAAs) glutamate and
      aspartate in the CSF dialysate were measured using high-performance liquid
      chromatography. RESULTS: Reduced astrocyte expression of glutamate transporters
      (GLT-1 and GLAST levels were 55% and 53%, respectively, of that in sham-operated
      rats) in laminae I and II of the spinal cord dorsal horn ipsilateral to the
      partial sciatic nerve transection (PST), and hyperalgesia and allodynia in the
      PST hindlimb were observed. High-dose naloxone (15 MUg) attenuated the
      antihyperalgesia and antiallodynia effects of the morphine (10 MUg). In contrast,
      ultra-low dose (15 ng) naloxone enhanced the antinociceptive effect of morphine
      (10 MUg), with an increase in the paw withdrawal threshold to thermal stimulus
      (from 19% to 35%) and to tactile stimulus (from 33% to 55%) compared with
      morphine treatment alone, and this was associated with restoration of GLAST and
      GLT-1 expression to control levels (102% and 114%, respectively) in the
      astrocytes of laminae I and II in the spinal cord dorsal horn ipsilateral to the
      PST hindlimb and a decrease in EAA levels in the CSF dialysate (glutamate: 10.0
      MUM; aspartate: 1.1 MUM). CONCLUSIONS: Ultra-low dose naloxone enhanced the
      antinociceptive effect of morphine in PST rats, possibly by restoration of GLAST
      and GLT-1 expression in astrocytes, which inhibited the accumulation of EAAs in
      the synapses, resulting in a neuroprotective effect.

PMID- 21865494
TI  - Allergic reactions during anesthesia at a large United States referral center.
AB  - BACKGROUND: The types of agents implicated to trigger intraoperative anaphylactic
      reactions vary among reports, and there are no recent series from the United
      States. In this retrospective study, we examined perioperative anaphylactic
      reactions that occurred at a major tertiary referral academic center. METHODS: To
      characterize perioperative allergens associated with anaphylactic reactions, we
      reviewed the Mayo Clinic Division of Allergic Diseases skin test database between
      1992 to 2010. The records of all patients who were tested for perioperative and
      anesthetic medications were reviewed. Charts that included a detailed history
      obtained by an allergist, skin test results, and tryptase measurements when
      available were reviewed and categorized. RESULTS: Thirty-eight patients were
      found to have an anaphylactic reaction during anesthesia, of which 18 were
      immunoglobulin (Ig)E-mediated anaphylactic reactions (likely causative agent
      identified by skin test), 6 were non-IgE-mediated anaphylactic reactions
      (elevated tryptase levels and negative skin test), and 14 were probable non-IgE
      mediated anaphylactic reactions (tryptase levels normal or not obtained and
      negative skin test). Of the IgE-mediated anaphylactic reactions, antibiotics were
      the most prevalent likely causative agent (50%) whereas neuromuscular blocking
      drugs were implicated as a likely causative agent in 11% of reactions.
      CONCLUSION: Antibiotics were the most common likely causative agent associated
      with IgE-mediated anaphylactic reactions; however, for 52.6% of reactions, a
      causative agent could not be determined, suggesting a non-IgE-mediated
      anaphylactic reaction. The undiagnosed allergic reactions place patients at risk
      of a subsequent reexposure to the same allergen, or lead to unnecessary avoidance
      of needed medications.

PMID- 21865495
TI  - Use of the BATHE method in the preanesthetic clinic visit.
AB  - BACKGROUND: In the primary care setting, use of the BATHE (Background, Affect,
      Trouble, Handling, and Empathy) method of interviewing has been shown to increase
      patient satisfaction. This technique is a brief psychotherapeutic method used to
      address patients' physical and psychosocial problems. The BATHE technique has not
      been evaluated in the perioperative setting as a way of improving patient
      satisfaction. In this study, we sought to determine whether satisfaction could be
      enhanced by use of the BATHE technique during the preoperative evaluation by
      anesthesiologists. METHODS: Fifty cardiac and 50 general surgery patients were
      interviewed in the preanesthesia clinic (PAC) of an academic hospital. They were
      randomly enrolled in the BATHE group or the control group and asked to complete
      an anonymous satisfaction survey after their visit. This survey was modified from
      current studies and not validated elsewhere. The relative influence of the BATHE
      condition was examined as it pertained to interview duration, patient
      satisfaction, and patient report of the BATHE items being asked. RESULTS: Ninety
      two percent of patients approached by the study group voluntarily enrolled.
      Patients interviewed using the BATHE method reported being asked about all BATHE
      questions significantly more often than control patients: t(98)=19.10, P=0.001
      (95% confidence interval [CI]=2.59, 3.20). Patients in the BATHE group were more
      satisfied with their visit to the PAC than those in the control group:
      t(98)=5.37, P=0.001 (95% CI=0.19, 0.41). The use of the BATHE method did not
      significantly increase the amount of time physicians spent evaluating patients:
      t(98)=0.110, P=0.912 (95% CI=-1.519, 1.359). CONCLUSIONS: Use of the BATHE method
      in an academic medical center's cardiac and general PAC showed promising results
      in this preliminary study. A validated and fully developed survey instrument is
      needed before we can convincingly conclude that the BATHE method is an effective
      way of improving patient satisfaction.

PMID- 21865496
TI  - Thoracic epidural bupivacaine attenuates inflammatory response, intestinal lipid
      peroxidation, oxidative injury, and mucosal apoptosis induced by mesenteric
      ischemia/reperfusion.
AB  - BACKGROUND: We conducted this study to evaluate the effects of thoracic epidural
      anesthesia (TEA) on inflammatory response, lipid peroxidation, and oxidative
      stress in a rat model of mesenteric ischemia/reperfusion (I/R). METHOD: Rats were
      divided into 4 groups: sham group (n=6; sham laparotomy), control group (n=6;
      I/R), bupivacaine group (n=6; mesenteric I/R and 20 MUL/h 0.5% bupivacaine), and
      saline group (n=6, mesenteric I/R and 20 MUL/h 0.9% saline). I/R injury was
      established by occluding the superior mesenteric artery for 1 hour followed by 12
      hours reperfusion. Blood gas, tumor necrosis factor-alpha, interleukin-6,
      interleukin-1beta, glutathione peroxidise, superoxide dismutase, catalese,
      myeloperoxidase concentrations, immunohistochemical examinations (intracellular
      adhesion molecule-1), apoptosis determination, and wet/dry ratio of intestinal
      edema were determined. RESULTS: Bupivacaine significantly decreased the cytokine,
      malondialdehyde, and myeloperoxidase levels and increased the antioxidant enzyme
      levels. Wet/dry ratio comparison showed a significant decrease in the bupivacaine
      (2.88+/-0.17) group in comparison with control (5.45+/-0.67) and saline (5.87+/
      0.17) groups. The intestinal injury score was significantly decreased in rats in
      the epidural bupivacaine (2 [1-2]) infusion group in comparison with rats in the
      control (3 [2-3]) and saline (3 [2-4]) groups. Bupivacaine (63%) caused a
      significant decrease in the percentage of apoptotic cells in comparison with
      control (85%) only. ICAM-1 levels in the bupivacaine (27.4+/-7.1) group decreased
      in comparison with control (12.3+/-7.4) and saline (24.9+/-3.2) groups.
      CONCLUSION: This study demonstrated that epidural bupivacaine attenuates the
      mesenteric I/R-related inflammatory response and intestinal damage.

PMID- 21865497
TI  - Limb remote postconditioning alleviates cerebral reperfusion injury through
      reactive oxygen species-mediated inhibition of delta protein kinase C in rats.
AB  - BACKGROUND: Remote ischemic postconditioning (RPostC) is an emerging concept for
      cerebral infarction protection, and its potential protective mechanisms have not
      been well established. We attempted to investigate the implications of reactive
      oxygen species (ROS) and delta protein kinase C (deltaPKC) in neuroprotection
      induced by RPostC in a rat model of focal cerebral ischemia, and also to explore
      a possible relationship between ROS and epsilonPKC. METHODS: Focal cerebral
      ischemia was induced by middle cerebral artery occlusion using the intraluminal
      filament technique in male rats. RPostC was generated by 3 10-minute cycles of
      femoral artery occlusion/reperfusion on the right limb at the onset of middle
      cerebral artery reperfusion. RPostC was performed alone or with pretreatment of N
      acetylcysteine, a ROS scavenger. In separate group, TAT-deltaV1-1, a deltaPKC
      selective peptide inhibitor, was administered at the onset of reperfusion. Brain
      ischemic injury was evaluated by neurologic scores, infarction volumes, and TUNEL
      staining. Moreover, the activation of deltaPKC in the ischemic penumbra was
      investigated by Western blot after reperfusion. RESULTS: RPostC improved
      neurologic outcome, reduced infarct size, and inhibited neuronal apoptosis as
      well as suppressed the activation of deltaPKC after reperfusion. Moreover,
      systemic delivery of TAT-deltaV1-1 conferred neuroprotection against cerebral
      reperfusion injury at the onset of reperfusion. Pretreatment with N
      acetylcysteine not only completely prevented all aspects of RPostC-induced
      neuroprotection, but also reversed RPostC-induced inhibition of deltaPKC
      activation after reperfusion. CONCLUSION: These findings suggested that RPostC
      performed in one limb alleviated reperfusion injury after focal cerebral ischemia
      through ROS-mediated inhibition of endogenous deltaPKC activation signaling
      cascade in an in vivo rat model of focal cerebral ischemia.

PMID- 21865498
TI  - The effect of lipid emulsion infusion on postmortem ropivacaine concentrations in
      swine: endeavoring to comprehend a soldier's death.
AB  - BACKGROUND: Lipid emulsion (20%) is advocated as a rescue drug for local
      anesthetic toxicity. No study has measured the impact of lipid emulsion therapy
      on postmortem local anesthetic serum levels. METHODS: We anesthetized Yorkshire
      swine (n = 11) and standard monitors were placed. The swine received 1.5
      mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before
      infusion (baseline) and at 5-minute intervals during the infusion for measurement
      of blood gases and free, bound, and total serum ropivacaine concentrations via
      high-performance liquid chromatography. Five swine received ropivacaine only, and
      6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1
      mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine
      infusions were terminated at asystole and no resuscitation was initiated. Total
      ropivacaine dose and time to death were recorded. The swine were cooled (mean
      temperature, 25.5 degrees C +/- 0.8 degrees C at 6 hours postmortem) to reflect
      morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours
      postmortem for analysis. Additionally, a craniotomy and laparotomy were performed
      at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and
      muscle for analysis. RESULTS: Analysis of the postmortem serum ropivacaine
      concentrations in the control and the lipid-treated animals indicated that both
      the total (bound and not bound to proteins) and free (not bound to proteins)
      ropivacaine concentrations were significantly higher in the lipid-treated animals
      (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant
      effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095).
      The lipid group had a statistically significant earlier onset of death (asystole)
      compared with the control group (P = 0.0274). Tissue analysis indicated that the
      ropivacaine concentration significantly decreased postmortem in the lung, kidney,
      and brain tissues of the lipid-treated animals (P = 0.0168, P = 0.0073, and P =
      0.0018, respectively). Tissue drug concentrations in the control animals remained
      unchanged after death. CONCLUSIONS: Our data show that postmortem blood samples
      in swine that experience local anesthetic cardiovascular collapse and are treated
      with lipid emulsions will result in measurements that cannot be directly
      extrapolated to premortem drug concentrations.

PMID- 21865499
TI  - Case report: Severe vasospasm mimics hypotension after high-dose intrauterine
      vasopressin.
AB  - Intramyometrial vasopressin injection reduces bleeding during myomectomy.
      Subsequent loss of peripheral pulses and nonmeasurable arterial blood pressure
      have been attributed to cardiovascular collapse or hypotension. When interpreted
      as global hypotension, treatment with vasopressors or according to Advanced
      Cardiac Life Support resuscitation protocols has been associated with cardiac
      complications. We describe a patient who developed loss of peripheral pulses and
      nonmeasurable blood pressure by noninvasive means after myometrial administration
      of 60 U vasopressin, with documented severe peripheral arterial vasospasm and
      elevated proximal blood pressure. We discuss the pathophysiology and emphasize
      the danger of misinterpreting pulselessness as global hypotension instead of
      vasospasm in this setting.

PMID- 21865500
TI  - Technical communication: An initial evaluation of a novel anesthetic scavenging
      interface.
AB  - Waste anesthetic gas scavenging technology has not changed appreciably in the
      past 30 years. Open reservoir systems entrain high volumes of room air and dilute
      waste gases before emission into the atmosphere. This process requires a large
      vacuum pump, which is both costly to install and, although efficient, operates
      continuously and at near-full capacity. In an era of increasing energy costs and
      environmental awareness, carbon footprint reduction is a priority and a more
      efficient system of safely scavenging waste anesthetic gases is desirable. We
      tested a low-flow scavenger interface to evaluate the potential for cost and
      energy savings. The use of this interface in a suite of 4 operating rooms reduced
      scavenging flow from a constant 37 L/min to a value equal to the fresh gas flow
      (usually 2 L/min) for each anesthesia machine. Using the ventilator increased
      this flow by approximately 6 L/min because of the exhaust of ventilator drive gas
      into the scavenging circuit. Daytime workload of the central vacuum pump
      decreased from 92% to 12% (expressed as duty cycle). The new system produces
      energy savings and may increase vacuum pump lifespan.

PMID- 21865501
TI  - A set of microsatellite primers for Zostera japonica (Zosteraceae).
AB  - PREMISE OF THE STUDY: Polymorphic microsatellite primers were developed in the
      seagrass Zostera japonica to investigate genetic variation and to identify clonal
      structure. * METHODS AND RESULTS: Thirteen polymorphic loci and 23 monomorphic
      loci were developed in Z. japonica. Two to 13 alleles per locus were observed at
      the polymorphic loci across 57 individuals of two Z. japonica populations. The
      observed and expected heterozygosities within populations ranged from 0.0000 to
      1.0000 and from 0.0000 to 0.8542, respectively. * CONCLUSIONS: Our study showed
      high-level polymorphism at the polymorphic loci in Z. japonica. These primers
      would be a powerful tool to study genetic variation, clonal structure, and mating
      systems.

PMID- 21865502
TI  - Microsatellite loci development in mycoheterotrophic Corallorhiza maculata
      (Orchidaceae) with amplification in C. mertensiana.
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for the first time
      in the species Corallorhiza maculata, a nonphotosynthetic orchid that is becoming
      a model for studying mycorrhizal specificity. * METHODS AND RESULTS: Eight
      polymorphic microsatellite markers were developed using an enrichment and cloning
      protocol. The number of alleles for each locus ranged from two to seven. The loci
      were tested in three populations, and the resulting high F(ST) values suggested
      that these loci have utility in illuminating population structure. Cross
      amplification was also achieved in the sister species C. mertensiana. *
      CONCLUSIONS: These microsatellite markers will be useful in further study of the
      population genetics of this species, including that of previously described
      mycorrhizal races.

PMID- 21865503
TI  - Isolation and characterization of microsatellite markers for a worldwide invasive
      weed, Chromolaena odorata (Asteraceae).
AB  - PREMISE OF THE STUDY: Microsatellite loci were isolated and characterized for a
      worldwide invasive weed Chromolaena odorata (Asteraceae) to elucidate the
      population genetic structure and invasive history. * METHODS AND RESULTS: A total
      of 14 microsatellite primer pairs were developed using the Fast Isolation by AFLP
      of Sequences Containing repeats (FIASCO) protocol, and their polymorphism was
      assessed in two natural populations of C. odorata from Mexico and Trinidad and
      Tobago. Eleven loci showed polymorphism and eight of these loci were successfully
      amplified in Ageratina adenophora, another invasive weed related to C. odorata. *
      CONCLUSIONS: These microsatellite markers are useful for investigating the
      population genetic structure and the history of range expansion of these invasive
      species.

PMID- 21865504
TI  - Xylem function and climate adaptation in Pinus.
AB  - PREMISE OF THE STUDY: The distribution of species is determined in part by their
      functional traits. One important function is the ability of xylem to supply water
      to leaves and withstand water-stress-induced cavitation. These hydraulic traits
      are hypothesized to have evolved in response to selection by precipitation and
      temperature. * METHODS: We grew 26 species in the genus Pinus in a common
      environment and used phylogenetic comparative methods to examine whether the
      evolution of seedling hydraulic and wood density traits were associated with the
      climate of the extant geographic range of the species. We also examined whether
      these traits were correlated with each other, with integrated water-use
      efficiency (WUE), and with plant growth. * KEY RESULTS: Contrary to predictions
      from a hydraulic model, we found no association between stem hydraulic
      conductivity (K(S)) and precipitation, even though there was substantial
      variation for K(S) in the genus. Nevertheless, K(S) was positively correlated
      with temperature, plant biomass, and WUE. Wood density was infrequently
      associated with climate or correlated with other traits except for plant biomass.
      * CONCLUSIONS: Reduced K(S) in cold climates, if associated with reduced conduit
      diameter, likely evolved to increase resistance to freezing-induced xylem
      cavitation. The absence of a K(S)-precipitation relationship among Pinus
      seedlings suggests that associations between hydraulic traits and precipitation
      found in adult trees arise through plastic responses to moisture availability
      and/or develop over ontogeny. The weak association among wood density, climate,
      and other traits suggest that this trait does not contribute to climate
      adaptation in Pinus.

PMID- 21865505
TI  - Genetic structure and phenotypic variation in wild populations of the medicinal
      tetraploid species Bromelia antiacantha (Bromeliaceae).
AB  - PREMISE OF THE STUDY: The patterns of genetic structure in plant populations are
      mainly related to the species life history and breeding system, and knowledge of
      these patterns is necessary for the management, use, and conservation of
      biological diversity. Polyploidy is considered an important mode of evolution in
      plants, but few studies have evaluated genetic structure of polyploid
      populations. We studied the patterns of genetic structure and morphological
      variation of Bromelia antiacantha (Bromeliaceae) populations, a polyploid
      terrestrial species. * METHODS: Microsatellite markers and morphological analyses
      were used to explore patterns of genetic and morphological diversity in wild
      populations of B. antiacantha. * KEY RESULTS: The results of our simple-sequence
      repeat analyses supported that B. antiacantha is a polyploid species. The
      inbreeding coefficients were high and significant in all populations (F(IS) =
      0.431), indicating homozygote excess. Bromelia antiacantha showed high levels of
      genetic differentiation among populations (F(ST) = 0.224) and therefore was
      highly structured. High morphological variation was observed in fruit phenotypic
      traits in the populations studied. * CONCLUSIONS: The levels of genetic diversity
      and the pattern of the population's structure may be related to the low
      recruitment of seeds, clonal reproduction, and the population's colonization
      history. The genetic and morphological variability displayed in this study are
      important issues in planning the conservation and exploitation of this resource
      in a sustainable way.

PMID- 21865506
TI  - From forest to field: perennial fruit crop domestication.
AB  - PREMISE OF THE STUDY: Archaeological and genetic analyses of seed-propagated
      annual crops have greatly advanced our understanding of plant domestication and
      evolution. Comparatively little is known about perennial plant domestication, a
      relevant topic for understanding how genes and genomes evolve in long-lived
      species, and how perennials respond to selection pressures operating on a
      relatively short time scale. Here, we focus on long-lived perennial crops (mainly
      trees and other woody plants) grown for their fruits. KEY RESULTS: We reviewed
      (1) the basic biology of long-lived perennials, setting the stage for perennial
      domestication by considering how these species evolve in nature; (2) the suite of
      morphological features associated with perennial fruit crops undergoing
      domestication; (3) the origins and evolution of domesticated perennials grown for
      their fruits; and (4) the genetic basis of domestication in perennial fruit
      crops. CONCLUSIONS: Long-lived perennials have lengthy juvenile phases, extensive
      outcrossing, widespread hybridization, and limited population structure. Under
      domestication, these features, combined with clonal propagation, multiple
      origins, and ongoing crop-wild gene flow, contribute to mild domestication
      bottlenecks in perennial fruit crops. Morphological changes under domestication
      have many parallels to annual crops, but with key differences for mating system
      evolution and mode of reproduction. Quantitative trait loci associated with
      domestication traits in perennials are mainly of minor effect and may not be
      stable across years. Future studies that take advantage of genomic approaches and
      consider demographic history will elucidate the genetics of agriculturally and
      ecologically important traits in perennial fruit crops and their wild relatives.

PMID- 21865507
TI  - Development and characterization of microsatellite markers in the critically
      endangered species Acer yangbiense (Aceraceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed to assess genetic
      diversity and population structure in Acer yangbiense, a critically endangered
      endemic species that occurs in northwestern Yunnan Province, China. * METHODS AND
      RESULTS: Using the Fast Isolation by AFLP of Sequences Containing repeats
      (FIASCO) protocol, 34 microsatellite loci were isolated and characterized in A.
      yangbiense. Polymorphisms were evaluated in 39 individuals from two distinct
      populations, one of which was naturally occurring and the other an ex situ
      grouping. Nine of the markers showed polymorphisms with two to five alleles per
      locus; observed (H(o)) and expected (H(e)) heterozygosities ranged from 0.0000 to
      0.8000 and from 0.0000 to 0.6889, respectively. * CONCLUSIONS: These
      microsatellite primers will prove useful in the further investigation of
      population genetics studies in A. yangbiense and, in addition, will assist
      related research of other congeneric species.

PMID- 21865508
TI  - Twelve-month mortality among delirium subtypes.
AB  - This study used data from the Delirium Among the Elderly in Rural Long-Term Care
      Facilities Study and data from the National Death Index (NDI) to examine
      mortality among 320 individuals. Individuals were grouped into noncases,
      subsyndromal cases, hypoactive delirium, hyperactive delirium, and mixed delirium
      on the basis of scoring using the Confusion Assessment Method (CAM), NEECHAM
      Scale, Mini-Mental State Examination (MMSE), Clinical Assessment of Confusion-A
      (CAC-A), and Vigilance A instruments. Risk ratios of mortality using "days of
      survival" did not reach statistical significance (alpha = .05) for any subgroup.
      Underlying cause of death (UCD) using International Classification of Disease,
      10th version (ICD-10), showed typical UCD among older adults. There appeared to
      be clinical differences in UCD between delirium subgroups. Findings supported the
      conclusion that careful monitoring of patients with delirium and subsyndromal
      delirium is needed to avoid complications and injuries that could increase
      mortality.

PMID- 21865509
TI  - The Company of Biologists' Workshop--Fish muscle growth and repair: models
      linking biomedicine and aquaculture.

PMID- 21865510
TI  - An exemplar of energy accounting: the energetics of the locust jump.

PMID- 21865511
TI  - Developmental expression of calcium transport proteins in extraembryonic
      membranes of oviparous and viviparous Zootoca vivipara (Lacertilia, Lacertidae).
AB  - The eggshell of oviparous lizards is a significant source of calcium for embryos,
      whereas the eggshell of viviparous lizards, when present, contains little
      calcium. In view of the potential cost to embryonic nutrition occasioned by the
      loss of eggshell calcium, the large number of independent origins of viviparity
      among lizards is surprising. Concomitant evolution of viviparity and calcium
      placentotrophy would ameliorate the loss of eggshell calcium, but a mechanism
      linking these events has yet to be discovered. Zootoca vivipara, a lizard with
      geographic variation in its mode of parity, is an excellent model for studying
      mechanisms of calcium transport to oviparous and viviparous embryos because each
      is highly dependent on calcium secreted by the uterus (eggshell or placenta) and
      ontogenetic patterns of embryonic calcium mobilization are similar. We compared
      developmental expression of the calcium transport protein calbindin-D(28K) in
      yolk splanchnopleure and chorioallantoic membranes of oviparous and viviparous
      embryos to test the hypothesis that the mechanism of calcium transport does not
      differ between modes of parity. We found that the ontogenetic pattern of protein
      expression is similar between reproductive modes and is correlated with calcium
      uptake from yolk and either eggshell or placenta. Calbindin-D(28K) is localized
      in the chorionic epithelium of embryos of both reproductive modes. These findings
      suggest that the embryonic calcium transport machinery is conserved in the
      transition between reproductive modes and that an adaptation of oviparous embryos
      for calcium uptake from eggshells functions similarly to transport calcium
      directly from uterine secretions.

PMID- 21865512
TI  - Hypoxia-induced mobilization of stored triglycerides in the euryoxic goby
      Gillichthys mirabilis.
AB  - Environmental hypoxia is a common challenge that many aquatic organisms
      experience in their habitat. Responding to hypoxia requires metabolic
      reprogramming so that energy-demanding processes are regulated to match available
      energy reserves. In this study we explored the transcriptional control of
      metabolic reorganization in the liver of a hypoxia-tolerant burrow-dwelling goby,
      Gillichthys mirabilis. Gene expression data revealed that pathways associated
      with triglyceride hydrolysis were upregulated by hypoxia whereas pathways
      associated with triglyceride synthesis were downregulated. This finding was
      supported by tissue histology, which showed that the size of hepatic lipid
      droplets declined visibly during exposure to hypoxia. Proton nuclear magnetic
      resonance analysis confirmed the mobilization of hepatic triglycerides, which
      declined 2.7-fold after 5 days of hypoxia. The enzyme, adipose triglyceride
      lipase, was implicated in the mobilization of triglycerides because its
      expression increased at the level of both transcript and protein. This
      observation raises questions regarding the regulation of fat metabolism during
      hypoxia and the role played by the hypoxia-responsive gene leptin.

PMID- 21865513
TI  - Evolution of limb bone loading and body size in varanid lizards.
AB  - Geometric scaling predicts that stresses on limb bones and muscles should
      increase with body size. Mammals counter this size-related increase in stress
      partially through changes in bone geometry, but largely through changes in
      posture, with larger species having a more erect stance. However, the ability to
      counter size-related stresses in this fashion may be limited to those taxa that
      have a parasagittal gait (such as mammals), where legs are swung underneath the
      body. We examined locomotor kinematics for 11 species of varanid lizards (from
      0.04 to 8 kg body mass) that have a sprawling gait, to determine how they
      moderate size-related stresses. Posture, as indicated by femur adduction and hip
      heights, did not change significantly with body size, beyond that expected from
      geometrical scaling. Instead, lizards mitigated size-related increases in stress
      by increasing duty factor and possibly reducing femur rotation. Incorporating
      these factors in biomechanical models predicted that both bending (?M(0.016),
      where M is mass) and torsional (?M(-0.049)) stresses should be nearly independent
      of body size over the size range examined. However, increasing duty factor and
      reducing femur rotation probably have deleterious effects on speed, and this
      difference in kinematics with size may explain why speed scales lower for
      sprawling lizards than for parasagittal mammals (?M(0.17) and ?M(0.24),
      respectively). Further, paralleling conclusions for the synapsid lineage, these
      findings suggest that evolution from sprawling to upright posture did not occur
      in archosaurs as a response to larger size; rather, these archosaurs likely
      became upright first and larger later.

PMID- 21865514
TI  - Cold-impaired cardiac performance in rats is only partially overcome by cold
      acclimation.
AB  - The consequences of acute hypothermia include impaired cardiovascular
      performance, ultimately leading to circulatory collapse. We examined the extent
      to which this results from intrinsic limitations to cardiac performance or
      physiological dysregulation/autonomic imbalance, and whether chronic cold
      exposure could ameliorate the impaired function. Wistar rats were held at a 12
      h:12 h light:dark (L:D) photoperiod and room temperature (21 degrees C; euthermic
      controls), or exposed to a simulated onset of winter in an environmental chamber
      by progressive acclimation to 1 h:23 h L:D and 4 degrees C over 4 weeks. In vivo,
      acute cold exposure (core temperature, T(b)=25 degrees C) resulted in hypotension
      (approximately -20%) due to low cardiac output (approximately -30%) accompanying
      a bradycardia (approximately -50%). Cold acclimation (CA) induced only partial
      compensation for this challenge, including increased coronary flow at T(b)=37
      degrees C (but not at T(b)=25 degrees C), maintenance of ventricular capillarity
      and altered sympathovagal balance (increased low:high frequency in power spectral
      analysis, PSA), suggesting physiological responses alone were insufficient to
      maintain cardiovascular performance. However, PSA showed maintenance of
      cardiorespiratory coupling on acute cold exposure in both groups. Ex vivo cardiac
      performance revealed no change in intrinsic heart rate, but a mechanical
      impairment of cardiac function at low temperatures following CA. While CA
      involved an increased capacity for beta-oxidation, there was a paradoxical
      reduction in developed pressure as a result of adrenergic down-regulation. These
      data suggest that integrated plasticity is the key to cardiovascular
      accommodation of chronic exposure to a cold environment, but with the potential
      for improvement by intervention, for example with agents such as non
      catecholamine inotropes.

PMID- 21865515
TI  - Learning the way to blood: first evidence of dual olfactory conditioning in a
      blood-sucking insect, Rhodnius prolixus. I. Appetitive learning.
AB  - It has been largely assumed that the individual experience of insects that are
      disease vectors might not only contribute to animal fitness, but also have an
      important influence on parasite transmission. Nevertheless, despite the invested
      efforts in testing the capacity to learn and remember information in blood
      sucking insects, only little conclusive information has been obtained to date.
      Adapting a classical conditioning approach to our haematophagous model, we
      trained larvae of Rhodnius prolixus to associate L-lactic-acid, an odour
      perceived by these bugs but behaviourally neutral when presented alone, with food
      (i.e. positive reinforcement). Naive bugs--those exposed either to a conditioned
      stimulus (CS, L-lactic acid), unconditioned stimulus (US, heat) and reward
      (blood) alone or CS, US and reward in the absence of contingency--remained
      indifferent to the presence of an air stream loaded with L-lactic acid when
      tested in an olfactometer (random orientation), whereas the groups previously
      exposed to the contingency CS-US-reward (blood) were significantly attracted by L
      lactic-acid. In a companion paper, the opposite, i.e. repellence, was induced in
      bugs exposed to the contingency of the same odour with a negative reinforcement.
      This constitutes the first evidence of olfactory conditioning in triatomine bugs,
      vectors of Chagas disease, and one of the few substantiations available to date
      of olfactory conditioning in haematophagous insects.

PMID- 21865516
TI  - Learning the way to blood: first evidence of dual olfactory conditioning in a
      blood-sucking insect, Rhodnius prolixus. II. Aversive learning.
AB  - After having demonstrated that blood-sucking bugs are able to associate a
      behaviourally neutral odour (L-lactic acid) with positive reinforcement (i.e.
      appetitive conditioning) in the first part of this study, we tested whether these
      insects were also able to associate the same odour with a negative reinforcement
      (i.e. aversive conditioning). Learned aversion to host odours has been repeatedly
      suggested as a determinant for the distribution of disease vectors among host
      populations. Nevertheless, no experimental evidence has been obtained so far.
      Adapting a classical conditioning approach to our haematophagous model, we
      trained larvae of Rhodnius prolixus to associate L-lactic acid, an odour
      perceived by bugs but behaviourally neutral when presented alone, with a
      mechanical perturbation (i.e. negative reinforcement). Naive bugs and bugs
      exposed to CS, punishment, or CS and punishment without contingency remained
      indifferent to the presence of an air stream loaded with L-lactic acid (random
      orientation on a locomotion compensator), whereas the groups previously exposed
      to the contingency CS-punishment were significantly repelled by L-lactic acid. In
      a companion paper, the opposite, i.e. attraction, was induced in bugs exposed to
      the contingency of the same odour with a positive reinforcement. These constitute
      the first pieces of evidence of olfactory conditioning in triatomine bugs and the
      first demonstration that the same host odour can be used by insects that are
      disease vectors to learn to recognize either a host to feed on or a potentially
      defensive one. The orientation mechanism during repulsion is also discussed in
      light of our results.

PMID- 21865517
TI  - Knowledgeable individuals lead collective decisions in ants.
AB  - Self-organisation underlies many collective processes in large animal groups,
      where coordinated patterns and activities emerge at the group level from local
      interactions among its members. Although the importance of key individuals acting
      as effective leaders has recently been recognised in certain collective
      processes, it is widely believed that self-organised decisions are evenly shared
      among all or a subset of individuals acting as decision-makers, unless there are
      significant conflicts of interests among group members. Here, we show that
      certain individuals are disproportionately influential in self-organised
      decisions in a system where all individuals share the same interests: nest site
      selection by the ant Temnothorax albipennis. Workers that visited a good
      available nest site prior to emigration (the familiar nest) memorised its
      location, and later used this memory to navigate efficiently and find that nest
      faster than through random exploration. Additionally, these workers relied on
      their private information to expedite individual decisions about the familiar
      nest. This conferred a bias in favour of familiar nests over novel nests during
      emigrations. Informed workers were shown to have a significantly greater share in
      both recruitment and transport to the familiar nest than naive workers. This
      suggests that they were the main determinants of the collective preference for
      familiar nests, and thus contributed greatly to enhance collective performance.
      Overall, these results indicate that self-organised decisions are not always
      evenly shared among decision-makers, even in systems where there are no conflicts
      of interest. Animal groups may instead benefit from well-informed, knowledgeable
      individuals acting as leaders in decisions.

PMID- 21865518
TI  - Effects of molting on the visual acuity of the blue crab, Callinectes sapidus.
AB  - In crustaceans with compound eyes, the corneal lens of each facet is part of the
      exoskeleton and thus shed during molting. Here we used an optomotor assay to
      evaluate the impact of molting on visual acuity (as measured by the minimum
      resolvable angle, alpha(min)) in the female blue crab, Callinectes sapidus. We
      found that visual acuity decreases substantially in the days prior to molting and
      is gradually recovered after molting. Four days prior to molting, alpha(min) was
      1.8 deg (N=5), a value approximating the best possible acuity in this species. In
      the 24 h before ecdysis occurred, alpha(min) increased to 15.0 deg (N=12),
      corresponding to an eightfold drop in visual acuity. Within 6 days after molting,
      alpha(min) returned to the pre-molting value. Micrographs of C. sapidus eyes
      showed that a gap between the corneal lens and the crystalline cone first
      appeared approximately 5 days prior to shedding and increased in width as the
      process progressed. This separation was likely responsible for the loss of visual
      acuity observed in behavioral tests. In blue crabs, mating is limited to the
      period of the female's pubertal molt, and a reduction in acuity during this time
      may have an effect on the sensory cues used in female mate choice. The results
      described here may be broadly applicable to all arthropods that molt and have
      particular importance for crustaceans that molt multiple times in their lifetime
      or have mating cycles that are paired with molting.

PMID- 21865519
TI  - Regulation of gas exchange and haemolymph pH in the cockroach Nauphoeta cinerea.
AB  - Ventilatory control of internal CO(2) plays an important role in regulating
      extracellular acid-base balance in terrestrial animals. While this phenomenon is
      well understood among vertebrates, the role that respiration plays in the acid
      base balance of insects is in need of much further study. To measure changes in
      insect haemolymph pH, we implanted micro pH optodes into the haemocoel of
      cockroaches (Nauphoeta cinerea). They were then exposed to normoxic, hypoxic,
      hyperoxic and hypercapnic atmospheres while their haemolymph pH, VCO(2) and
      abdominal ventilation frequency were measured simultaneously. Intratracheal O(2)
      levels were also measured in separate experiments. It was found that cockroaches
      breathing continuously control their ventilation to defend a haemolymph pH of
      7.3, except under conditions where hypoxia (<10% O(2)) induces hyperventilation,
      or where ambient hypercapnia is in excess of haemolymph (>1% CO(2)). In contrast,
      intratracheal O(2) levels fluctuated widely, but on average remained above 15% in
      normoxic (21% O(2)) atmospheres. Decapitation caused the cockroaches to display
      discontinuous gas exchange cycles (DGCs). The alternating periods of ventilation
      and apnoea during DGCs caused haemolymph pH to fluctuate by 0.11 units. Exposure
      to hypoxia caused haemolymph pH to increase and initiated brief bouts of
      spiracular opening prior to the active ventilation phase. The spontaneous
      occurrence of DGCs in decapitated cockroaches indicates that central pattern
      generators in the thoracic and abdominal ganglia generate the periodic gas
      exchange pattern in the absence of control from the cephalic ganglion. This
      pattern continues to maintain gas exchange, but with less precision.

PMID- 21865520
TI  - Exceptional aerobic scope and cardiovascular performance of pink salmon
      (Oncorhynchus gorbuscha) may underlie resilience in a warming climate.
AB  - Little is known of the physiological mechanisms underlying the effects of climate
      change on animals, yet it is clear that some species appear more resilient than
      others. As pink salmon (Oncorhynchus gorbuscha) in British Columbia, Canada, have
      flourished in the current era of climate warming in contrast to other Pacific
      salmonids in the same watershed, this study investigated whether the continuing
      success of pink salmon may be linked with exceptional cardiorespiratory
      adaptations and thermal tolerance of adult fish during their spawning migration.
      Sex-specific differences existed in minimum and maximum oxygen consumption rates
      (M(O2,min) and M(O2,max), respectively) across the temperature range of 8 to 28
      degrees C, reflected in a higher aerobic scope (M(O2,max)-M(O2,min)) for males.
      Nevertheless, the aerobic scope of both sexes was optimal at 21 degrees C
      (T(opt)) and was elevated across the entire temperature range in comparison with
      other Pacific salmonids. As T(opt) for aerobic scope of this pink salmon
      population is higher than in other Pacific salmonids, and historic river
      temperature data reveal that this population rarely encounters temperatures
      exceeding T(opt), these findings offer a physiological explanation for the
      continuing success of this species throughout the current climate-warming period.
      Despite this, declining cardiac output was evident above 17 degrees C, and
      maximum attainable swimming speed was impaired above ~23 degrees C, suggesting
      negative implications under prolonged thermal exposure. While forecasted summer
      river temperatures over the next century are likely to negatively impact all
      Pacific salmonids, we suggest that the cardiorespiratory capacity of pink salmon
      may confer a selective advantage over other species.

PMID- 21865522
TI  - Magnetic orientation of migratory robins, Erithacus rubecula, under long
      wavelength light.
AB  - The avian magnetic compass is an inclination compass that appears to be based on
      radical pair processes. It requires light from the short-wavelength range of the
      spectrum up to 565 nm green light; under longer wavelengths, birds are
      disoriented. When pre-exposed to longer wavelengths for 1 h, however, they show
      oriented behavior. This orientation is analyzed under 582 nm yellow light and 645
      nm red light in the present study: while the birds in spring prefer northerly
      directions, they do not show southerly tendencies in autumn. Inversion of the
      vertical component does not have an effect whereas reversal of the horizontal
      component leads to a corresponding shift, indicating that a polar response to the
      magnetic field is involved. Oscillating magnetic fields in the MHz range do not
      affect the behavior but anesthesia of the upper beak causes disorientation. This
      indicates that the magnetic information is no longer provided by the radical pair
      mechanism in the eye but by the magnetite-based receptors in the skin of the
      beak. Exposure to long-wavelength light thus does not expand the spectral range
      in which the magnetic compass operates but instead causes a different mechanism
      to take over and control orientation.

PMID- 21865523
TI  - Behavioural and kinematic components of the fast-start escape response in fish:
      individual variation and temporal repeatability.
AB  - Inter-individual variation in physiological performance traits, which is stable
      over time, can be of potential ecological and evolutionary significance. The fish
      escape response is interesting in this regard because it is a performance trait
      for which inter-individual variation may determine individual survival. The
      temporal stability of such variation is, however, largely unexplored. We
      quantified individual variation of various components of the escape response in a
      population of European sea bass (Dicentrarchus labrax), considering both non
      locomotor (responsiveness and latency) and locomotor (speed, acceleration,
      turning rate, turning angle and distance travelled in a fixed time, D(esc))
      variables. We assessed whether variation in performance was temporally stable and
      we searched for any trade-offs among the components of the response that might
      explain why the variation persisted in the population. The coefficient of
      variation was high for all components, from 23% for turning rate to 41% for
      D(esc), highlighting the non-stereotypic nature of the response. Individual
      performance for all variables was significantly repeatable over five sequential
      responses at 30 min intervals, and also repeatable after a 30 day interval for
      most of the components. This indicates that the variation is intrinsic to the
      individuals, but there was no evidence for trade-offs amongst the components of
      the response, suggesting that, if trade-offs exist, they must be against other
      ecologically important behavioural or performance traits.

PMID- 21865521
TI  - Subglottal pressure and fundamental frequency control in contact calls of
      juvenile Alligator mississippiensis.
AB  - Vocalization is rare among non-avian reptiles, with the exception of the
      crocodilians, the sister taxon of birds. Crocodilians have a complex vocal
      repertoire. Their vocal and respiratory system is not well understood but appears
      to consist of a combination of features that are also found in the extremely
      vocal avian and mammalian taxa. Anatomical studies suggest that the alligator
      larynx is able to abduct and adduct the vocal folds, but not to elongate or
      shorten them, and is therefore lacking a key regulator of frequency, yet
      alligators can modulate fundamental frequency remarkably well. We investigated
      the morphological and physiological features of sound production in alligators.
      Vocal fold length scales isometrically across a wide range of alligator body
      sizes. The relationship between fundamental frequency and subglottal pressure is
      significant in some individuals at some isolated points, such as call onset and
      position of maximum fundamental frequency. The relationship is not consistent
      over large segments of the call. Fundamental frequency can change faster than
      expected by pressure changes alone, suggesting an active motor pattern controls
      frequency and is intrinsic to the larynx. We utilized a two-mass vocal fold model
      to test whether abduction and adduction could generate this motor pattern. The
      fine-tuned interplay between subglottal pressure and glottal adduction can
      achieve frequency modulations much larger than those resulting from subglottal
      pressure variations alone and of similar magnitude, as observed in alligator
      calls. We conclude that the alligator larynx represents a sound source with only
      two control parameters (subglottal pressure and vocal fold adduction) in contrast
      to the mammalian larynx in which three parameters can be altered to modulate
      frequency (subglottal pressure, vocal fold adduction and length/tension).

PMID- 21865524
TI  - Movement and function of the pectoral fins of the larval zebrafish (Danio rerio)
      during slow swimming.
AB  - Pectoral fins are known to play important roles in swimming for many adult fish;
      however, their functions in fish larvae are unclear. We examined routine pectoral
      fin movement during rhythmic forward swimming and used genetic ablation to test
      hypotheses of fin function in larval zebrafish. Fins were active throughout bouts
      of slow swimming. Initiation was characterized by asymmetric fin abduction that
      transitioned to alternating rhythmic movement with first fin adduction. During
      subsequent swimming, fin beat amplitude decreased while tail beat amplitude
      increased over swimming speeds ranging from 1.47 to 4.56 body lengths per second.
      There was no change in fin or tail beat frequency with speed (means +/- s.d.:
      28.2+/-3.5 and 29.6+/-1.9 Hz, respectively). To examine potential roles of the
      pectoral fins in swimming, we compared the kinematics of finless larvae generated
      with a morpholino knockdown of the gene fgf24 to those of normal fish. Pectoral
      fins were not required for initiation nor did they significantly impact forward
      rhythmic swimming. We investigated an alternative hypothesis that the fins
      function in respiration. Dye visualization demonstrated that pectoral fin beats
      bring distant fluid toward the body and move it caudally behind the fins,
      disrupting the boundary layer along the body's surface, a major site of oxygen
      absorption in larvae. Larval zebrafish also demonstrated more fin beating in low
      oxygen conditions. Our data reject the hypothesis that the pectoral fins of
      larval zebrafish have a locomotor function during slow, forward locomotion, but
      are consistent with the hypothesis that the fins have a respiratory function.

PMID- 21865525
TI  - jShaw1, a low-threshold, fast-activating K(v)3 from the hydrozoan jellyfish
      Polyorchis penicillatus.
AB  - Voltage-gated potassium (K(v)) channels work in concert with other ion channels
      to determine the frequency and duration of action potentials in excitable cells.
      Little is known about K(v)3 channels from invertebrates, but those that have been
      characterized generally display slow kinetics. Here, we report the cloning and
      characterization of jShaw1, the first K(v)3 isolated from a cnidarian, the
      jellyfish Polyorchis penicillatus, in comparison with mouse K(v)3.1 and K(v)3.2.
      Using a two-electrode voltage clamp on Xenopus laevis oocytes expressing the
      channels, we compared steady-state and kinetic properties of macroscopic
      currents. jShaw1 is fast activating, and opens at potentials approximately 40 mV
      more hyperpolarized than the mouse K(v)3 channels. There is an inverse
      relationship between the number of positive charges on the voltage sensor and the
      half-activation voltage of the channel, contrary to what would be expected with
      the simplest model of voltage sensitivity. jShaw1 has kinetic characteristics
      that are substantially different from the mammalian K(v)3 channels, including a
      much lower sensitivity of early activation rates to incremental voltage changes,
      and a much faster voltage-dependent transition in the last stages of opening.
      jShaw1 opening kinetics were affected little by pre-depolarization voltage, in
      contrast to both mouse channels. Similar to the mouse channels, jShaw1 was half
      blocked by 0.7 mmol l(-1) tetraethyl ammonium and 5 mmol l(-1) 4-aminopyridine.
      Comparison of sequence and functional properties of jShaw1 with the mouse and
      other reported K(v)3 channels helps to illuminate the general relationship
      between amino acid sequence and electrophysiological activity in this channel
      family.

PMID- 21865526
TI  - The spatial and temporal patterns of odors sampled by lobsters and crabs in a
      turbulent plume.
AB  - Odors are dispersed across aquatic habitats by turbulent water flow as
      filamentous, intermittent plumes. Many crustaceans sniff (take discrete samples
      of ambient water and the odors it carries) by flicking their olfactory
      antennules. We used planar laser-induced fluorescence to investigate how flicking
      antennules of different morphologies (long antennules of spiny lobsters,
      Panulirus argus; short antennules of blue crabs, Callinectes sapidus) sample
      fluctuating odor signals at different positions in a turbulent odor plume in a
      flume to determine whether the patterns of concentrations captured can provide
      information about an animal's position relative to the odor source. Lobster
      antennules intercept odors during a greater percentage of flicks and encounter
      higher peak concentrations than do crab antennules, but because crabs flick at
      higher frequency, the duration of odor-free gaps between encountered odor pulses
      is similar. For flicking antennules there were longer time gaps between odor
      encounters as the downstream distance to the odor source decreases, but shorter
      gaps along the plume centerline than near the edge. In contrast to the case for
      antennule flicking, almost all odor-free gaps were <500 ms at all positions in
      the plume if concentration was measured continuously at the same height as the
      antennules. Variance in concentration is lower and mean concentration is greater
      near the substratum, where leg chemosensors continuously sample the plume, than
      in the water where antennules sniff. Concentrations sampled by legs increase as
      an animal nears an odor source, but decrease for antennules. Both legs and
      antennules encounter higher concentrations near the centerline than at the edge
      of the plume.

PMID- 21865527
TI  - Religiosity and major depression in adults at high risk: a ten-year prospective
      study.
AB  - OBJECTIVE: Previously the authors found that personal importance of religion or
      spirituality was associated with a lower risk for major depression in a study of
      adults with and without a history of depression. Here the authors examine the
      association of personal importance of religion or spirituality with major
      depression in the adult offspring of the original sample using a 10-year
      prospective longitudinal design. METHOD: Participants were 114 adult offspring of
      depressed and nondepressed parents, followed longitudinally. The analysis covers
      the period from the 10-year to the 20-year follow-up assessments. Diagnosis was
      assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime
      Version. Religiosity measures included personal importance of religion or
      spirituality, frequency of attendance at religious services, and denomination
      (all participants were Catholic or Protestant). In a logistic regression
      analysis, major depression at 20 years was used as the outcome measure and the
      three religiosity variables at 10 years as predictors. RESULTS: Offspring who
      reported at year 10 that religion or spirituality was highly important to them
      had about one-fourth the risk of experiencing major depression between years 10
      and 20 compared with other participants. Religious attendance and denomination
      did not significantly predict this outcome. The effect was most pronounced among
      offspring at high risk for depression by virtue of having a depressed parent; in
      this group, those who reported a high importance of religion or spirituality had
      about one-tenth the risk of experiencing major depression between years 10 and 20
      compared with those who did not. The protective effect was found primarily
      against recurrence rather than onset of depression. CONCLUSIONS: A high self
      report rating of the importance of religion or spirituality may have a protective
      effect against recurrence of depression, particularly in adults with a history of
      parental depression.

PMID- 21865528
TI  - The study of fear extinction: implications for anxiety disorders.
AB  - In this review, the authors propose that the fear extinction model can be used as
      an experimental tool to cut across symptom dimensions of multiple anxiety
      disorders to enhance our understanding of the psychopathology of these disorders
      and potentially facilitate the detection of biomarkers for them. The authors
      evaluate evidence for this proposition from studies examining the neurocircuitry
      underlying fear extinction in rodents, healthy humans, and clinical populations.
      The authors also assess the potential use of the fear extinction model to predict
      vulnerability for anxiety and treatment response and to improve existing
      treatments or develop novel ones. Finally, the authors suggest potential
      directions for future research that will help to further validate extinction as a
      biomarker for anxiety across diagnostic categories and to bridge the gap between
      basic neuroscience and clinical practice.

PMID- 21865529
TI  - Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the
      effects of age and stimulant medication.
AB  - OBJECTIVE: Structural neuroimaging studies in attention-deficit hyperactivity
      disorder (ADHD) have been relatively inconsistent and have mainly been conducted
      with pediatric samples. Furthermore, there is evidence that stimulant medication
      may have an effect on brain structure. The authors conducted a meta-analysis of
      voxel-based morphometry studies in children and adults with ADHD and examined the
      potential effects of age and stimulant medication on regional gray matter
      volumes. METHOD: The PubMed, ScienceDirect, Web of Knowledge, and Scopus
      databases were searched for articles published between 2001 and 2011. Manual
      searches were also conducted, and authors of studies were contacted for
      additional data. Coordinates were extracted from clusters of significant gray
      matter difference between ADHD patients and healthy comparison subjects.
      Metaregression methods were used to explore potential age and stimulant
      medication effects. RESULTS: Fourteen data sets comprising 378 patients with ADHD
      and 344 healthy subjects met inclusion criteria. The ADHD group had global
      reductions in gray matter volumes, which were robustly localized in the right
      lentiform nucleus and extended to the caudate nucleus. Both increasing age and
      percentage of patients taking stimulant medication were found to be independently
      associated with more normal values in this region. Patients also had slightly
      greater gray matter volumes in the left posterior cingulate cortex. CONCLUSIONS:
      These findings confirm that the most prominent and replicable structural
      abnormalities in ADHD are in the basal ganglia. They furthermore suggest that
      ADHD patients may progressively catch up with their developmental delay with
      advancing age and that use of stimulant medication may be associated with
      normalization of structural abnormalities in ADHD, although longitudinal studies
      are needed to confirm both observations.

PMID- 21865530
TI  - Interaction of FKBP5 gene variants and adverse life events in predicting
      depression onset: results from a 10-year prospective community study.
AB  - OBJECTIVE: The binding protein FKBP5 is an important modulator of the function of
      the glucocorticoid receptor, the main receptor of the stress hormone system. This
      turns the FKBP5 gene into a key candidate for gene-environment interactions,
      which are considered critical for pathogenesis of stress-related disorders. The
      authors explored gene-environment interactions between FKBP5 gene variants and
      adverse life events in predicting the first occurrence of a major depressive
      episode. METHOD: The analyses were based on 884 Caucasians in a 10-year
      prospective community study. At baseline, they were 14-24 years old and did not
      fulfill criteria for a major depressive episode. The DSM-IV-based Munich
      Composite International Diagnostic Interview was used to assess adverse life
      events preceding baseline and major depressive episodes during follow-up. On the
      basis of previous findings, five single-nucleotide polymorphisms (SNPs) within
      the FKBP5 gene were selected for genotyping. RESULTS: While the authors did not
      observe genetic main effects, they found interactions between the five SNPs and
      traumatic (but not separation) events, with the strongest effect for severe
      trauma. The effect of trauma on incident major depressive episodes was evident
      among subjects homozygous for the minor alleles but not subjects with other
      genotypes. The findings were replicated in the U.K. Environmental Risk
      Longitudinal Twin Study. CONCLUSIONS: These hypothesis-driven results suggest
      that an interaction between FKBP5 genotype and trauma is involved in the onset of
      depression. Subjects homozygous for the minor alleles of the investigated FKBP5
      SNPs seem to be particularly sensitive to effects of trauma exposure in terms of
      triggering depression onset.

PMID- 21865532
TI  - Statistics, probability, significance, likelihood: words mean what we define them
      to mean.

PMID- 21865533
TI  - Ventricular remodelling in prediabetes: the heart of the matter!

PMID- 21865535
TI  - Herding cats.
AB  - The U.S. National Institutes of Health's new National Center for Advancing
      Translational Sciences (NCATS) should be refocused to spur innovation and renamed
      in a way that doesn't further polarize the scientific community. This Commentary
      offers some suggestions for both types of transformations.

PMID- 21865534
TI  - Emerging roles for gasotransmitters.

PMID- 21865536
TI  - A tale of two SCIDs.
AB  - Hematopoietic stem cell (HSC) transplantation may be curative for severe combined
      immunodeficiency (SCID). However, for a majority of infants with SCID a suitable
      donor is not available, and even with a matched donor, allogeneic HSC
      transplantation itself carries potential complications such as graft-versus-host
      disease as well as side effects from myelosuppressive chemotherapy. In the past
      decade, substantial advances have been made in the transplantation of gene
      modified autologous HSCs, especially for two forms of SCID: X-linked SCID (SCID
      X1) and adenosine deaminase (ADA)-deficient SCID. Two new reports in this issue
      of Science Translational Medicine add to the accumulating findings from gene
      therapy trials in Italy, France, and the United States that show clinical
      benefits of this alternative treatment.

PMID- 21865537
TI  - Long-term persistence of a polyclonal T cell repertoire after gene therapy for X
      linked severe combined immunodeficiency.
AB  - X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the
      common cytokine receptor gamma chain. These mutations classically lead to
      complete absence of functional T and natural killer cell lineages as well as to
      intrinsically compromised B cell function. Although human leukocyte antigen (HLA)
      matched hematopoietic stem cell transplantation (HSCT) is highly successful in
      SCID-X1 patients, HLA-mismatched procedures can be associated with prolonged
      immunodeficiency, graft-versus-host disease, and increased overall mortality.
      Here, 10 children were treated with autologous CD34(+) hematopoietic stem and
      progenitor cells transduced with a conventional gammaretroviral vector. The
      patients did not receive myelosuppressive conditioning and were monitored for
      immunological recovery after cell infusion. All patients were alive after a
      median follow-up of 80 months (range, 54 to 107 months), and a functional
      polyclonal T cell repertoire was restored in all patients. Humoral immunity only
      partially recovered but was sufficient in some patients to allow for withdrawal
      of immunoglobulin replacement; however, three patients developed antibiotic
      responsive acute pulmonary infection after discontinuation of antibiotic
      prophylaxis and/or immunoglobulin replacement. One patient developed acute T cell
      acute lymphoblastic leukemia because of up-regulated expression of the proto
      oncogene LMO-2 from insertional mutagenesis, but maintained a polyclonal T cell
      repertoire through chemotherapy and entered remission. Therefore, gene therapy
      for SCID-X1 without myelosuppressive conditioning effectively restored T cell
      immunity and was associated with high survival rates for up to 9 years. Further
      studies using vectors designed to limit mutagenesis and strategies to enhance B
      cell reconstitution are warranted to define the role of this treatment modality
      alongside conventional HSCT for SCID-X1.

PMID- 21865538
TI  - Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe
      combined immunodeficiency leads to long-term immunological recovery and metabolic
      correction.
AB  - Genetic defects in the purine salvage enzyme adenosine deaminase (ADA) lead to
      severe combined immunodeficiency (SCID) with profound depletion of T, B, and
      natural killer cell lineages. Human leukocyte antigen-matched allogeneic
      hematopoietic stem cell transplantation (HSCT) offers a successful treatment
      option. However, individuals who lack a matched donor must receive mismatched
      transplants, which are associated with considerable morbidity and mortality.
      Enzyme replacement therapy (ERT) for ADA-SCID is available, but the associated
      suboptimal correction of immunological defects leaves patients susceptible to
      infection. Here, six children were treated with autologous CD34-positive
      hematopoietic bone marrow stem and progenitor cells transduced with a
      conventional gammaretroviral vector encoding the human ADA gene. All patients
      stopped ERT and received mild chemotherapy before infusion of gene-modified
      cells. All patients survived, with a median follow-up of 43 months (range, 24 to
      84 months). Four of the six patients recovered immune function as a result of
      engraftment of gene-corrected cells. In two patients, treatment failed because of
      disease-specific and technical reasons: Both restarted ERT and remain well. Of
      the four reconstituted patients, three remained off enzyme replacement. Moreover,
      three of these four patients discontinued immunoglobulin replacement, and all
      showed effective metabolic detoxification. All patients remained free of
      infection, and two cleared problematic persistent cytomegalovirus infection.
      There were no adverse leukemic side effects. Thus, gene therapy for ADA-SCID is
      safe, with effective immunological and metabolic correction, and may offer a
      viable alternative to conventional unrelated donor HSCT.

PMID- 21865539
TI  - Potent kinetic stabilizers that prevent transthyretin-mediated cardiomyocyte
      proteotoxicity.
AB  - A valine-to-isoleucine mutation at position 122 of the serum protein
      transthyretin (TTR), found in 3 to 4% of African Americans, alters its stability,
      leading to amyloidogenesis and cardiomyopathy. In addition, 10 to 15% of
      individuals older than 65 years develop senile systemic amyloidosis and cardiac
      TTR deposits because of wild-type TTR amyloidogenesis. Although several drugs are
      in development, no approved therapies for TTR amyloid cardiomyopathy are yet
      available, so the identification of additional compounds that prevent amyloid
      mediated cardiotoxicity is needed. To this aim, we developed a fluorescence
      polarization-based high-throughput screen and used it to identify several new
      chemical scaffolds that target TTR. These compounds were potent kinetic
      stabilizers of TTR and prevented TTR tetramer dissociation, partial unfolding,
      and aggregation of both wild type and the most common cardiomyopathy-associated
      TTR mutant, V122I-TTR. High-resolution co-crystal structures and characterization
      of the binding energetics revealed how these diverse structures bound to
      tetrameric TTR. These compounds effectively inhibited the proteotoxicity of V122I
      TTR toward human cardiomyocytes. Several of these ligands stabilized TTR in human
      serum more effectively than diflunisal, which is a well-studied inhibitor of TTR
      aggregation, and may be promising leads for the treatment or prevention of TTR
      mediated cardiomyopathy.

PMID- 21865540
TI  - Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal
      "bitter taste" cue.
AB  - The discovery that cells in the gastrointestinal (GI) tract express the same
      molecular receptors and intracellular signaling components known to be involved
      in taste has generated great interest in potential functions of such post-oral
      "taste" receptors in the control of food intake. To determine whether taste cues
      in the GI tract are detected and can directly influence behavior, the present
      study used a microbehavioral analysis of intake, in which rats drank from
      lickometers that were programmed to simultaneously deliver a brief yoked infusion
      of a taste stimulus to the intestines. Specifically, in daily 30-min sessions,
      thirsty rats with indwelling intraduodenal catheters were trained to drink
      hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M
      NaCl solution. Once trained, in a subsequent series of intestinal taste probe
      trials, rats reduced licking during a 6-min infusion period, when a bitter
      stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for
      infusion, apparently conditioning a mild taste aversion. Presentation of the DB
      in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the
      development of the response across trials and strengthened the temporal
      resolution of the early licking suppression in response to the arrival of the DB
      in the intestine. In an experiment to evaluate whether CCK is involved as a
      paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist
      devazepide partially blocked the response to intestinal DB. In contrast to their
      ability to detect and avoid the bitter taste in the intestine, rats did not
      modify their licking to saccharin intraduodenal probe infusions. The intestinal
      taste aversion paradigm developed here provides a sensitive and effective
      protocol for evaluating which tastants-and concentrations of tastants-in the
      lumen of the gut can control ingestion.

PMID- 21865541
TI  - Regulation of apical H+-ATPase activity and intestinal HCO3- secretion in marine
      fish osmoregulation.
AB  - The absorption of Cl(-) and water from ingested seawater in the marine fish
      intestine is accomplished partly through Cl(-)/HCO(3)(-) exchange. Recently, a
      H(+) pump (vacuolar-type H(+)-ATPase) was found to secrete acid into the
      intestinal lumen, and it may serve to titrate luminal HCO(3)(-) and facilitate
      further Cl(-)/HCO(3)(-) exchange, especially in the posterior intestine, where
      adverse concentration gradients could limit Cl(-)/HCO(3)(-) exchange. The H(+)
      pump is expressed in all intestinal segments and in gill tissue of gulf toadfish
      (Opsanus beta) maintained in natural seawater. After acute transfer of toadfish
      to 60 ppt salinity, H(+) pump expression increased 20-fold in the posterior
      intestine. In agreement with these observations was a fourfold-increased H(+)
      ATPase activity in the posterior intestine of animals acclimated to 60 ppt
      salinity. Interestingly, Na(+)-K(+)-ATPase activity was elevated in the anterior
      intestine and gill, but not in the posterior intestine. Apical acid secretion by
      isolated intestinal tissue mounted in Ussing chambers fitted with pH-stat
      titration systems increased after acclimation to hypersalinity in the anterior
      and posterior intestine, titrating >20% of secreted bicarbonate. In addition, net
      base secretion increased in hypersalinity-acclimated fish and was ~70% dependent
      on serosal HCO(3)(-). Protein localization by immunohistochemistry confirmed the
      presence of the vacuolar-type H(+)-ATPase in the apical region of intestinal
      enterocytes. These results show that the H(+) pump, especially in the posterior
      intestine, plays an important role in hypersaline osmoregulation and that it
      likely has significant effects on HCO(3)(-) accumulation in the intestinal lumen
      and, therefore, the continued absorption of Cl(-) and water.

PMID- 21865542
TI  - Skeletal muscle proteomics: carbohydrate metabolism oscillates with seasonal and
      torpor-arousal physiology of hibernation.
AB  - The physiology of small mammalian hibernators shifts profoundly over a year, from
      summer homeothermy to winter heterothermy. Torpor-arousal cycles define high
      amplitude tissue activity fluctuations in winter, particularly for skeletal
      muscle, which contributes to the energetically demanding rewarming process via
      shivering. To better understand the biochemistry underlying summer-winter and
      torpor-arousal transitions, we applied two-dimensional gel electrophoresis
      coupled with liquid chromatography/mass spectrometry/mas spectrometry to the
      soluble proteins from hindlimb muscle of 13-lined ground squirrels (Ictidomys
      tridecemlineatus) in two summer and six winter states. Two hundred sixteen
      protein spots differed by sampled state. Significantly, intrawinter protein
      adjustment was a minor component of the dataset despite large discrepancies in
      muscle activity level among winter states; rather, the bulk of differences
      (127/138 unequivocally identified proteins spots) occurred between summer and
      winter. We did not detect any proteomic signatures of skeletal muscle atrophy in
      this hibernator nor any differential seasonal regulation of protein metabolism.
      Instead, adjustments to metabolic substrate preferences dominated the detected
      proteomic differences. Pathways of carbohydrate metabolism (glycolysis and
      gluconeogenesis) were summer enriched, whereas the winter proteome was enriched
      for fatty acid beta-oxidation. Nevertheless, our data suggest that some reliance
      on carbohydrate reserves is maintained during winter. Phosphoglucomutase (PGM1),
      which reversibly prepares glucose subunits for either glycolysis or glycogenesis,
      showed apparent winter state-specific phosphorylation. PGM1 was phosphorylated
      during rewarming and dephosphorylated by interbout arousal, implying that glucose
      supplements lipid fuels during rewarming. This, along with winter elevation of
      TCA cycle enzymes, suggests that hindlimb muscles are primed for rapid energy
      production and that carbohydrates are an important fuel for shivering
      thermogenesis.

PMID- 21865544
TI  - Impact of L-NAME on the cardiopulmonary reflex in cardiac hypertrophy.
AB  - There is evidence that in cardiac failure, there is defective baroreceptor reflex
      control of sympathetic nerve activity. Often, cardiac failure is preceded by a
      state of cardiac hypertrophy in which there may be enhanced performance of the
      heart. This study investigated whether in two different models of cardiac
      hypertrophy, there was an increased contribution of nitric oxide (NO) to the low
      pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) and
      nerve-dependent excretory function. Administration of a volume load, 0.25* body
      wt/min saline for 30 min, in normal rats decreased RSNA by 40* and increased
      urine flow by some 9-fold. Following nitro-L-arginine methyl ester (L-NAME)
      administration, 10 MUg.kg(-1).min(-1) for 60 min, which had no effect on blood
      pressure, heart rate, or RSNA, the volume load-induced renal sympathoinhibitory
      and excretory responses were markedly enhanced. In cardiac hypertrophy states
      induced by 2 wk of isoprenaline/caffeine or 1 wk thyroxine administration, the
      volume challenge failed to suppress RSNA, and there were blunted increases in
      urine flow in the innervated kidneys, but following L-NAME infusion, the volume
      load decreased RSNA by 30-40* and increased urine flow by some 20-fold in the
      innervated kidneys, roughly to the same extent as observed in normal rats. These
      findings suggest that the blunted renal sympathoinhibition and nerve-dependent
      diuresis to the volume load in cardiac hypertrophy are related to a heightened
      production or activity of NO within either the afferent or central arms of the
      reflex.

PMID- 21865543
TI  - Hypercholesterolemia increases mitochondrial oxidative stress and enhances the
      MPT response in the porcine myocardium: beneficial effects of chronic exercise.
AB  - Hypercholesterolemia has been suggested to have direct negative effects on
      myocardial function due to increased reactive oxygen species (ROS) generation and
      increased myocyte death. Mitochondrial permeability transition (MPT) is a
      significant mediator of cell death, which is enhanced by ROS generation and
      attenuated by exercise training. The purpose of this study was to investigate the
      effect of hypercholesterolemia on the MPT response of cardiac mitochondria. We
      tested the hypothesis that familial hypercholesterolemic (FH) pigs would have an
      enhanced MPT response and that exercise training could reverse this phenotype.
      MPT was assessed by mitochondrial swelling in response to 10-100 MUM Ca(2+). FH
      pigs did show an increased MPT response to Ca(2+) that was associated with
      decreases in the expression of the putative MPT pore components mitochondrial
      phosphate carrier (PiC) and cyclophilin-D (CypD). FH also caused increased
      oxidative stress, depicted by increased protein nitrotyrosylation, as well as
      decreased levels of reduced GSH in cardiac mitochondria. Expression of the
      mitochondrial antioxidant enzymes manganese superoxide dismutase (MnSOD),
      thioredoxin-2 (Trx2), and peroxiredoxin-3 (Prx3) was greatly reduced in the FH
      pigs. In contrast, cytosolic catalase expression and activity were increased.
      However, chronic exercise training was able to normalize the MPT response in FH
      pigs, reduce mitochondrial oxidative stress, and return MnSOD, Trx2, Prx3, and
      catalase expression/activities to normal. We conclude that FH reduces
      mitochondrial antioxidants, increases mitochondrial oxidative stress, and
      enhances the MPT response in the porcine myocardium, and that exercise training
      can reverse these detrimental alterations.

PMID- 21865546
TI  - Thermal acclimation in Antarctic fish: transcriptomic profiling of metabolic
      pathways.
AB  - It is widely accepted that adaptation to the extreme cold has evolved at the
      expense of high thermal sensitivity. However, recent studies have demonstrated
      significant capacities for warm acclimation in Antarctic fishes. Here, we report
      on hepatic metabolic reorganization and its putative molecular background in the
      Antarctic eelpout (Pachycara brachycephalum) during warm acclimation to 5 degrees
      C over 6 wk. Elevated capacities of cytochrome c oxidase suggest the use of warm
      acclimation pathways different from those in temperate fish. The capacity of this
      enzyme rose by 90%, while citrate synthase (CS) activity fell by 20% from the
      very beginning. The capacity of lipid oxidation by hydroxyacyl-CoA dehydrogenase
      remained constant, whereas phosphoenolpyruvate carboxykinase as a marker for
      gluconeogenesis displayed 40% higher activities. These capacities in relation to
      CS indicate a metabolic shift from lipid to carbohydrate metabolism. The finding
      was supported by large rearrangements of the related transcriptome, both
      functional genes and potential transcription factors. A multivariate analysis
      (canonical correspondence analyses) of various transcripts subdivided the
      incubated animals in three groups, one control group and two responding on short
      and long timescales, respectively. A strong dichotomy in the expression of
      peroxisome proliferator-activated receptors-1alpha and -beta receptors was most
      striking and has not previously been reported. Altogether, we identified a
      molecular network, which responds sensitively to warming beyond the realized
      ecological niche. The shift from lipid to carbohydrate stores and usage may
      support warm hardiness, as the latter sustain anaerobic metabolism and may
      prepare for hypoxemic conditions that would develop upon warming beyond the
      present acclimation temperature.

PMID- 21865545
TI  - Angiotensin II potentiates adrenergic and muscarinic modulation of guinea pig
      intracardiac neurons.
AB  - The intrinsic cardiac plexus represents a major peripheral integration site for
      neuronal, hormonal, and locally produced neuromodulators controlling efferent
      neuronal output to the heart. This study examined the interdependence of
      norepinephrine, muscarinic agonists, and ANG II, to modulate intrinsic cardiac
      neuronal activity. Intracellular voltage recordings from whole-mount preparations
      of the guinea pig cardiac plexus were used to determine changes in active and
      passive electrical properties of individual intrinsic cardiac neurons.
      Application of either adrenergic or muscarinic agonists induced changes in
      neuronal resting membrane potentials, decreased afterhyperpolarization duration
      of single action potentials, and increased neuronal excitability. Adrenergic
      responses were inhibited by removal of extracellular calcium ions, while
      muscarinic responses were inhibited by application of TEA. The adrenergic
      responses were heterogeneous, responding to a variety of receptor-specific
      agonists (phenylephrine, clonidine, dobutamine, and terbutaline), although alpha
      receptor agonists produced the most frequent responses. Application of ANG II
      alone produced a significant increase in excitability, while application of ANG
      II in combination with either adrenergic or muscarinic agonists produced a much
      larger potentiation of excitability. The ANG II-induced modulation of firing was
      blocked by the angiotensin type 2 (AT(2)) receptor inhibitor PD 123319 and was
      mimicked by the AT(2) receptor agonist CGP-42112A. AT(1) receptor blockade with
      telmasartin did not alter neuronal responses to ANG II. These data demonstrate
      that ANG II potentiates both muscarinically and adrenergically mediated
      activation of intrinsic cardiac neurons, doing so primarily via AT(2) receptor
      dependent mechanisms. These neurohumoral interactions may be fundamental to
      regulation of neuronal excitability within the intrinsic cardiac nervous system.

PMID- 21865547
TI  - Induction of heme oxygenase-1 attenuates sFlt-1-induced hypertension in pregnant
      rats.
AB  - Preeclampsia (PE) is one of the leading causes of fetal and maternal morbidity,
      affecting 5-10% of all pregnancies, and lacks an effective treatment. The exact
      etiology of the disorder is unclear, but placental ischemia has been shown to be
      a central causative agent. In response to placental ischemia, the antiangiogenic
      protein fms-like tyrosine kinase-1 (sFlt-1), a VEGF antagonist, and reactive
      oxygen species are secreted, leading to the maternal syndrome. One promising
      therapeutic approach to treat PE is through manipulation of the heme oxygenase-1
      (HO-1) protein. It has been previously reported that HO-1 and carbon monoxide
      downregulate sFlt-1 production in vitro, and we have recently shown that HO-1
      induction significantly attenuates placental ischemia-induced hypertension,
      partially through normalization of the sFlt-1-to-VEGF ratio in the placenta. The
      purpose of this study was to determine whether HO-1 induction would have
      beneficial effects independently of sFlt-1 suppression. To that end, pregnant
      rats were continuously infused with recombinant sFlt-1 from gestational days 14
      19, and circulating sFlt-1 increased approximately twofold, similar to rats with
      experimentally induced placental ischemia. In response, mean arterial pressure
      increased 17 mmHg, which was completely normalized by HO-1 induction. Unbound
      circulating VEGF was decreased ~17% in response to sFlt-1 infusion but was
      increased ~50% in response to HO-1 induction. Finally, endothelial function was
      improved as measured by reductions in vascular expression of preproendothelin
      mRNA. In conclusion, manipulation of HO-1 presents an intriguing therapeutic
      approach to the treatment of PE.

PMID- 21865548
TI  - Cutting edge: mouse CD300f (CMRF-35-like molecule-1) recognizes outer membrane
      exposed phosphatidylserine and can promote phagocytosis.
AB  - Reportedly, CD300f negatively regulates interactions between dendritic and T
      cells and acts as an anti-inflammatory molecule in a multiple sclerosis mouse
      model. We found that a CD300f/Fc chimeric protein specifically binds to
      apoptotic/dead splenocytes and to apoptotic cells from starved or irradiated
      lymphocytic cell lines, an observation extended to insect cells. CD300f also
      binds PMA/ionomycin-activated splenocytes and Ag-stimulated T cells, an
      interaction inhibited by Annexin V. By ELISA, cosedimentation, and surface
      plasmon resonance using phospholipid-containing liposomes, we show that CD300f
      preferentially binds phosphatidylserine and requires a metal ion. Exogenous
      expression of CD300f in cell lines results in enhanced phagocytosis of apoptotic
      cells. We conclude that expression of CD300f conveys additional capacity to
      recognize phosphatidylserine to myeloid cells. The result of this recognition may
      vary with the overall qualitative and quantitative receptor content, as well as
      signaling capacity of the expressing effector cell, but enhanced phagocytosis is
      one measurable outcome.

PMID- 21865549
TI  - Genome-wide expression profiling and mutagenesis studies reveal that
      lipopolysaccharide responsiveness appears to be absolutely dependent on TLR4 and
      MD-2 expression and is dependent upon intermolecular ionic interactions.
AB  - Lipid A (a hexaacylated 1,4' bisphosphate) is a potent immune stimulant for
      TLR4/MD-2. Upon lipid A ligation, the TLR4/MD-2 complex dimerizes and initiates
      signal transduction. Historically, studies also suggested the existence of
      TLR4/MD-2-independent LPS signaling. In this article, we define the role of TLR4
      and MD-2 in LPS signaling by using genome-wide expression profiling in TLR4- and
      MD-2-deficient macrophages after stimulation with peptidoglycan-free LPS and
      synthetic Escherichia coli lipid A. Of the 1396 genes significantly induced or
      repressed by any one of the treatments in the wild-type macrophages, none was
      present in the TLR4- or MD-2-deficient macrophages, confirming that the TLR4/MD-2
      complex is the only receptor for endotoxin and that both are required for
      responses to LPS. Using a molecular genetics approach, we investigated the
      mechanism of TLR4/MD-2 activation by combining the known crystal structure of
      TLR4/MD-2 with computer modeling. According to our murine TLR4/MD-2-activation
      model, the two phosphates on lipid A were predicted to interact extensively with
      the two positively charged patches on mouse TLR4. When either positive patch was
      abolished by mutagenesis into Ala, the responses to LPS and lipid A were nearly
      abrogated. However, the MyD88-dependent and -independent pathways were impaired
      to the same extent, indicating that the adjuvant activity of monophosphorylated
      lipid A most likely arises from its decreased potential to induce an active
      receptor complex and not more downstream signaling events. Hence, we concluded
      that ionic interactions between lipid A and TLR4 are essential for optimal LPS
      receptor activation.

PMID- 21865550
TI  - Low-dose antigen promotes induction of FOXP3 in human CD4+ T cells.
AB  - Low Ag dose promotes induction and persistence of regulatory T cells (Tregs) in
      mice, yet few studies have addressed the role of Ag dose in the induction of
      adaptive CD4(+)FOXP3(+) Tregs in humans. To this end, we examined the level of
      FOXP3 expression in human CD4(+)CD25(-) T cells upon activation with autologous
      APCs and varying doses of peptide. Ag-specific T cells expressing FOXP3 were
      identified by flow cytometry using MHC class II tetramer (Tmr). We found an
      inverse relationship between Ag dose and the frequency of FOXP3(+) cells for both
      foreign Ag-specific and self Ag-specific T cells. Through studies of FOXP3 locus
      demethylation and helios expression, we determined that variation in the
      frequency of Tmr(+)FOXP3(+) T cells was not due to expansion of natural Tregs,
      but instead, we found that induction, proliferation, and persistence of FOXP3(+)
      cells was similar in high- and low-dose cultures, whereas proliferation of FOXP3(
      ) T cells was favored in high Ag dose cultures. The frequency of FOXP3(+) cells
      positively correlated with suppressive function, indicative of adaptive Treg
      generation. The frequency of FOXP3(+) cells was maintained with IL-2, but not
      upon restimulation with Ag. Together, these data suggest that low Ag dose favors
      the transient generation of human Ag-specific adaptive Tregs over the
      proliferation of Ag-specific FOXP3(-) effector T cells. These adaptive Tregs
      could function to reduce ongoing inflammatory responses and promote low-dose
      tolerance in humans, especially when Ag exposure and tolerance is transient.

PMID- 21865551
TI  - The P2X7 receptor and Pannexin-1 are both required for the promotion of
      multinucleated macrophages by the inflammatory cytokine GM-CSF.
AB  - The P2X(7) receptor (P2X(7)R), an ATP-gated ion channel, has been implicated in
      the process of cell-to-cell fusion into multinucleated macrophages (MA), but its
      contribution to MA fusion driven by physiological/pathological stimuli is not
      clearly established. Based on several lines of evidence, we demonstrate that
      P2X(7)R is critical for the induction of multinucleated MA by the inflammatory
      cytokine GM-CSF: 1) pharmacological inhibition of P2X(7)R with oxidized ATP
      (oATP), KN-62, and the selective antagonist A740003 abrogated GM-CSF action on
      rat alveolar MA and murine peritoneal MA; 2) a murine J774 P2X(7) low MA clone,
      selected for defective P2X(7)R function, was unresponsive; 3) MA from mice
      lacking P2X(7)R failed to respond to GM-CSF, in contrast to wild-type. GM-CSF
      also stimulated ATP-induced membrane permeabilization in J774 P2X(7) high MA and
      rat alveolar MA, an effect absent in the P2X(7) low MA clone and inhibited by the
      P2X(7) blockers oATP and KN-62. Notably, the stimulatory effects of GM-CSF on
      pore formation and MA fusion were both inhibited by blocking functional Pannexin
      1 (Panx-1), and GM-CSF failed to stimulate MA fusion in cells from Panx-1
      knockout mice. We provide further evidence that extracellular ATP release from
      peritoneal MA is dependent on P2X(7) but not on Panx-1 expression and that its
      metabolism to adenosine mediates P2X(7)-dependent MA fusion. These data
      demonstrate that both P2X(7) and Panx-1 are required for GM-CSF promotion of MA
      fusion but likely act independently through different signaling pathway(s).

PMID- 21865552
TI  - The role of mannose-binding lectin-associated serine protease-3 in activation of
      the alternative complement pathway.
AB  - Mannose-binding lectin (MBL)-associated serine proteases (MASPs) are responsible
      for activation of the lectin complement pathway. Three types of MASPs (MASP-1,
      MASP-2, and MASP-3) are complexed with MBL and ficolins in serum. Although MASP-1
      and MASP-2 are known to contribute to complement activation, the function of MASP
      3 remains unclear. In this study, we investigated the mechanism of MASP-3
      activation and its substrate using the recombinant mouse MASP-3 (rMASP-3) and
      several different types of MASP-deficient mice. A proenzyme rMASP-3 was obtained
      that was not autoactivated during preparation. The recombinant enzyme was
      activated by incubation with Staphylococcus aureus in the presence of MBL-A, but
      not MBL-C. In vivo studies revealed the phagocytic activities of MASP-1/3
      deficient mice and all MASPs (MASP-1/2/3)-deficient mice against S. aureus and
      bacterial clearance in these mice were lower than those in wild-type and MASP-2
      deficient mice. Sera from all MASPs-deficient mice showed significantly lower C3
      deposition activity on the bacteria compared with that of wild-type serum, and
      addition of rMASP-3 to the deficient serum restored C3 deposition. The low C3
      deposition in sera from all MASPs-deficient mice was probably caused by the low
      level factor B activation that was ameliorated by the addition of rMASP-3.
      Furthermore, rMASP-3 directly activated factors B and D in vitro. These results
      suggested that MASP-3 complexed with MBL is converted to an active form by
      incubation with bacterial targets, and that activated MASP-3 triggered the
      initial activation step of the alternative complement pathway.

PMID- 21865554
TI  - Loss of cysteine-rich secretory protein 4 (Crisp4) leads to deficiency in sperm
      zona pellucida interaction in mice.
AB  - Mammalian sperm gain their ability to fertilize the egg during transit through
      the epididymis and by interacting with proteins secreted by the epididymal
      epithelial cells. Certain members of the CRISP (cysteine-rich secretory protein)
      family form the major protein constituent of the luminal fluid in the mammalian
      epididymis. CRISP4 is the newest member of the CRISP family expressed
      predominantly in the epididymis. Its structure and expression pattern suggest a
      role in sperm maturation and/or sperm-egg interaction. To study the relevance of
      CRISP4 in reproduction, we have generated a Crisp4 iCre knock-in mouse model
      through insertion of the iCre recombinase coding cDNA into the Crisp4 locus. This
      allows using the mouse line both as a Crisp4 deficient model and as an epididymis
      specific iCre-expressing mouse line applicable for the generation of conditional,
      epididymis-specific knockout mice. We show that the loss of CRISP4 leads to a
      deficiency of the spermatozoa to undergo progesterone-induced acrosome reaction
      and to a decreased fertilizing ability of the sperm in the in vitro fertilization
      conditions, although the mice remain fully fertile in normal mating. However,
      removal of the egg zona pellucida returned the fertilization potential of the
      CRISP4-deficient spermatozoa, and accordingly we detected a reduced number of
      Crisp4-deficient spermatozoa bound to oocytes as compared with the wild-type
      spermatozoa. We also demonstrate that iCre recombinase is expressed in a pattern
      similar to endogenous Crisp4 and is able to initiate the recombination event with
      its target sequences in vivo.

PMID- 21865553
TI  - Aging results in differential regulation of DNA repair pathways in pachytene
      spermatocytes in the Brown Norway rat.
AB  - The present trend of increasing paternal age is accompanied by concerns for the
      development of complex multigene diseases (e.g., autism and schizophrenia) in
      progeny. Recent studies have established strong correlations between male age,
      increased oxidative stress, decreased sperm quality, and structural aberrations
      of chromatin and DNA in spermatozoa. We tested the hypothesis that increasing age
      would result in altered gene expression relating to oxidative stress and DNA
      damage/repair in germ cells. To test this hypothesis, pachytene spermatocytes and
      round spermatids were isolated from Brown Norway (BN) rats at 4 (young) and 18
      (aged) mo of age. Microarray analysis was used to compare gene expression between
      the groups. The probe sets with significantly altered expression were linked to
      DNA damage/repair and oxidative stress in pachytene spermatocytes but not in
      round spermatids. Further analysis of pachytene spermatocytes demonstrated that
      genes involved in the base excision repair (BER) and nucleotide excision repair
      (NER) pathways were specifically altered. Quantitative RT-PCR confirmed that NER
      genes were upregulated (>1.5-fold), whereas BER genes were downregulated (>1.5
      fold). At the protein level the members of the BER pathway were also altered by
      up to 2.3-fold; levels of NER proteins remained unchanged. Furthermore, there was
      an increase in 8-oxo-2'-deoxyguanosine (8-oxodG) immunoreactivity in testes from
      aged males and in the number of spermatozoa positive for 8-oxodG. In conclusion,
      aging is associated with differential regulation of DNA repair pathways with a
      decrease in the BER pathway leading to deficient repair of 8-oxo-dG lesions in
      germ cells and spermatozoa.

PMID- 21865555
TI  - Comparative transcriptome analysis of human trophectoderm and embryonic stem cell
      derived trophoblasts reveal key participants in early implantation.
AB  - The implantation process begins with attachment of the trophectoderm (TE) of the
      blastocyst to the maternal endometrial epithelium. Herein we have investigated
      the transcriptome of mural TE cells from 13 human blastocysts and compared these
      with those of human embryonic stem cell (hESC)-derived-TE (hESC(troph)). The
      transcriptomes of hESC(troph) at Days 8, 10, and 12 had the greatest consistency
      with TE. Among genes coding for secreted proteins of the TE of human blastocysts
      and of hESC(troph) are several molecules known to be involved in the implantation
      process, as well as novel ones, such as CXCL12, HBEGF, inhibin A, DKK3, WNT5A,
      and follistatin. The similarities between the two lineages underscore some of the
      known mechanisms and offer discovery of new mechanisms and players in the process
      of the very early stages of human implantation. We propose that the hESC(troph)
      is a viable functional model of human trophoblasts to study trophoblast
      endometrial interactions. Furthermore, the data derived herein offer the promise
      of novel diagnostics and therapeutics aimed at practical challenges in human
      infertility and pregnancy disorders associated with abnormal embryonic
      implantation.

PMID- 21865556
TI  - Uterine histotroph and conceptus development: select nutrients and secreted
      phosphoprotein 1 affect mechanistic target of rapamycin cell signaling in ewes.
AB  - Interferon tau (IFNT), the pregnancy recognition signal in ruminants, abrogates
      the uterine luteolytic mechanism to ensure maintenance of function for the
      corpora lutea to produce progesterone (P4). IFNT also suppresses expression of
      classical IFN-stimulated genes by uterine lumenal epithelium (LE) and superficial
      glandular (sGE) epithelium but, acting in concert with progesterone, affects
      expression of a multitude of genes critical to growth and development of the
      conceptus. The LE and sGE secrete proteins and transport nutrients into the
      uterine lumen necessary for conceptus development, pregnancy recognition
      signaling, and implantation. Secretions include arginine and secreted
      phosphoprotein 1 (SPP1). Arginine can be metabolized to nitric oxide and to
      polyamines or act directly to activate the mechanistic target of rapamycin cell
      signaling pathway to stimulate proliferation, migration, and mRNA translation in
      trophectoderm cells. SPP1 binds alphavbeta3 and alpha5beta1 integrins to induce
      focal adhesion assembly, adhesion, and migration of conceptus trophectoderm cells
      during implantation. Thus, arginine and SPP1 mediate growth, migration,
      cytoskeletal remodeling, and adhesion of trophectoderm essential for pregnancy
      recognition signaling and implantation. This minireview focuses on components of
      histotroph that affect conceptus development in the ewe.

PMID- 21865558
TI  - Divalent minerals decrease micellarization and uptake of carotenoids and
      digestion products into Caco-2 cells.
AB  - Carotenoids are lipophilic, dietary antioxidants with the potential to prevent
      chronic and age-related diseases. Prior to their availability for physiological
      functions, carotenoids require micellarization and intestinal uptake, both
      constituting marginally understood processes. Based on an in vitro digestion
      model coupled to Caco-2 cells, we assessed the effect of dietary abundant
      divalent ions on spinach-derived carotenoid micellarization and cellular uptake:
      Ca and Mg ranging from 7.5 to 25 mmol/L in the digesta and Zn and Fe ranging from
      3.8 to 12.5 mmol/L. Both micellarization and uptake were significantly inhibited
      by minerals in a concentration-dependent manner, with stronger effects for Fe and
      Zn compared to Ca and Mg. Compared to controls (no mineral addition), fractional
      micellarization and uptake were decreased to the greatest extent (to 22.5 and
      5.0%, respectively; P < 0.001) by 12.5 mmol/L Fe. Effects of Mg were of the least
      magnitude; at 25 mmol/L, only uptake was decreased significantly to 69.2% of the
      control value (P < 0.001). Total cellular carotenoid uptake from test meals
      decreased similarly compared to micellarization; however, decreased beta-carotene
      micellarization was counterbalanced by improved fractional cellular uptakes from
      the micelles for all ions. Compared to controls, fractional beta-carotene uptake
      from the micelles was greater in samples digested in the presence of Fe, Ca, and
      Zn, by up to 5-10 times at the highest concentrations of each ion (P < 0.001).
      Like for the above carotenoids, a high cellular uptake of the epoxycarotenoid
      conversion products neochrome (from neoxanthin) and luteoxanthin+auroxanthin
      (from violaxanthin) was also observed. The present results indicate that divalent
      ions may inhibit carotenoid micellarization and uptake.

PMID- 21865557
TI  - Age-dependent susceptibility of chromosome cohesion to premature separase
      activation in mouse oocytes.
AB  - A hypothesis to explain the maternal age-dependent increase in formation of
      aneuploid eggs is deterioration of chromosome cohesion. Although several lines of
      evidence are consistent with this hypothesis, whether cohesion is actually
      reduced in naturally aged oocytes has not been directly tested by any
      experimental perturbation. To directly target cohesion, we increased the activity
      of separase, the protease that cleaves the meiotic cohesin REC8, in oocytes. We
      show that cohesion is more susceptible to premature separase activation in old
      oocytes than in young oocytes, demonstrating that cohesion is significantly
      reduced. Furthermore, cohesion is protected by two independent mechanisms that
      inhibit separase, securin and an inhibitory phosphorylation of separase by CDK1;
      both mechanisms must be disrupted to prematurely activate separase. With the
      continual loss of cohesins from chromosomes that occurs throughout the natural
      reproductive lifespan, tight regulation of separase in oocytes may be
      particularly important to maintain cohesion and prevent aneuploidy.

PMID- 21865559
TI  - Cholesterol-absorber status modifies the LDL cholesterol-lowering effect of a
      Mediterranean-type diet in adults with moderate cardiovascular risk factors.
AB  - LDL-cholesterol (LDL-C) reduction may be achieved by various types of prudent
      diets, but their effects on surrogate markers of cholesterol absorption and
      synthesis have not been well studied in humans. We aimed to assess whether the
      extent of cholesterol absorption or synthesis, and cholesterol concentrations,
      are modified in adults when they shift from a Western-type diet (WD) to a
      combined low-fat, low-cholesterol/Mediterranean-type diet (LFCMD). Cholestanol
      and sitosterol, as well as desmosterol and lathosterol, surrogate markers of
      cholesterol absorption or synthesis, respectively, were quantified in the serum
      of 125 fasting, middle-aged participants at moderate cardiovascular risk. They
      habitually consumed a WD and then consumed a LFCMD during the 3-mo intervention.
      The group was stratified by serum cholestanol concentration and classified as
      high, intermediate, or low absorbers of cholesterol. When they consumed the WD,
      participants had comparable total and LDL-C concentrations, independent of
      absorber group and sex. After 3 mo of consuming the LFCMD, absorption and
      synthesis did not change or changed only slightly. The cholestanol concentration
      increased in low absorbers by 18% (P < 0.02) and decreased in high absorbers by
      14% (P < 0.001), but these variations did not change the high- or low-absorber
      status. In male and female low absorbers, plasma total (-7%) and LDL-C (-9%)
      concentrations decreased after the 3-mo intervention and changes were 2.3- and
      2.4-fold greater, respectively, than in high absorbers, independent of sex.
      Cholesterol synthesis/absorption status was not markedly altered by diet, but the
      decrease in plasma LDL-C due to the Mediterranean-type diet occurred only in low
      absorbers of cholesterol. This should be considered during further dietary
      interventions.

PMID- 21865560
TI  - Opportunities for small nutrition-related cancer research grants (R03) from the
      National Cancer Institute.
AB  - Small research grants, or R03 grants, provide limited, short-term support for
      individual research projects. R03s may be an excellent means of support for
      projects by nutrition scientists at all stages in their careers. The National
      Cancer Institute (NCI) has awarded roughly one-half of all nutrition-related NIH
      R03 grants in the period from 2005 to 2010. A detailed review of the recent NCI
      grant portfolio identified potential strategies for successful applications.
      Projects that addressed important nutrition and cancer issues had feasible and
      appropriate specific aims, were innovative, and were based on sound concepts were
      most positively viewed by reviewers. Furthermore, applicants with suitable
      expertise, training, mentorship, and records of accomplishment who, when
      appropriate, collaborated with investigators with complementary knowledge and
      skills were more likely to receive higher priority scores.

PMID- 21865561
TI  - Transcobalamin polymorphism 67A->G, but not 776C->G, affects serum
      holotranscobalamin in a cohort of healthy middle-aged men and women.
AB  - Two polymorphic variants in the gene coding for transcobalamin II (TCN2), TCN2
      776C- > G and TCN2 67A- > G, may alter serum holotranscobalamin (holoTC), which
      in turn may affect cellular uptake of cobalamin (Cbl) and thereby Cbl status
      indicators. We studied the effects of TCN2 776C- > G and TCN2 67A- > G on blood
      concentrations of holoTC, Cbl, methylmalonic acid (MMA), and total homocysteine
      (tHcy) in 2411 individuals (50-64 y) that had been selected on the basis of these
      TCN2 genotypes from 10601 Norwegian inhabitants. The serum holoTC concentration
      was lower in TCN2 67AG (55 +/- 0.75 pmol/L) and 67GG (48 +/- 2.14 pmol/L) than in
      67AA (62 +/- 0.67 pmol/L) (P < 0.001) but did not differ among TCN2 776C- > G
      genotypes. The polymorphisms interacted as serum holoTC determinants (P = 0.001)
      and the presence of TCN2 67AG and GG in strata of 776CC and CG, but not 776GG,
      increased the risk of having serum holoTC < 45.6 pmol/L [tertile 1 vs. tertiles 2
      and 3: OR = 2.5 (95% CI 1.8-3.5) for 67AG; OR = 5.7 (95% CI 3.5-9.1) for 67GG in
      776CC; OR = 2.1 (95% CI 1.6-2.9) for 67AG; and OR = 4.5 (95% CI 2.4-8.2) for 67GG
      in 776CG; all P < 0.001]. Plasma MMA, tHcy, and Cbl were not affected by either
      polymorphism. In summary, serum holoTC, but not plasma Cbl, MMA, or tHcy, varied
      according to TCN2 67A- > G genotypes. It remains to be determined whether this
      polymorphic effect on serum holoTC alters its diagnostic utility as Cbl status
      indicator.

PMID- 21865562
TI  - Dietary patterns are associated with stroke in Chinese adults.
AB  - We recently featured Chinese dietary patterns that were associated with obesity,
      hyperglycemia, hypertension, and metabolic syndrome. In this study, we examined
      the association of those dietary patterns and risk of stroke among 26,276 Chinese
      adults aged >=45 y by using data from the 2002 China National Nutrition and
      Health Survey and explored whether those associations were mediated by obesity,
      hypertension, hyperglycemia, and other cardiovascular risk factors. The
      traditional southern Chinese dietary pattern, characterized by high intakes of
      rice and vegetables and moderate intakes in animal foods, was related to the
      lowest prevalence of stroke. Compared to the traditional southern dietary
      pattern, the traditional northern Chinese dietary pattern, characterized by high
      intakes of refined cereal products, potatoes, and salted vegetables, was
      associated with an elevated risk of stroke [OR = 1.96 (95% CI = 1.48-2.60); P <
      0.0001]. Adjustment for conventional cardiovascular risk factors did not
      appreciably change the association [multivariate adjusted OR = 1.59 (95%CI = 1.16
      2.17); P = 0.004]. The Western dietary pattern characterized by high consumption
      of beef, fruit, eggs, poultry, and seafood is also associated with an elevated
      risk of stroke [OR = 2.36 (95%CI = 1.82-3.06); P < 0.0001], but the associations
      became nonsignificant after adjustment for obesity, hypertension, hyperglycemia,
      and dyslipidemia. In conclusion, we found that the traditional southern dietary
      pattern was related to low prevalence of stroke and the traditional northern
      dietary pattern was associated with an increased stroke risk. The Western dietary
      patterns also association with high risk of stroke, which was largely mediated by
      obesity, hypertension, hyperglycemia, and dyslipidemia.

PMID- 21865563
TI  - Low maternal vitamin B-12 status is associated with offspring insulin resistance
      regardless of antenatal micronutrient supplementation in rural Nepal.
AB  - Questions have been raised about potentially negative effects of antenatal folic
      acid use in populations with a high prevalence of vitamin B-12 deficiency. Our
      objective was to examine the association between maternal folate and vitamin B-12
      status in pregnancy on offspring insulin resistance and examine whether the
      effects of maternal micronutrient supplementation varied by baseline maternal
      folate and/or vitamin B-12 status. Pregnant women were cluster randomized to
      receive daily supplements containing vitamin A alone or with folic acid, folic
      acid+iron, folic acid+iron+zinc, or a multiple micronutrient. In a subsample (n =
      1132), micronutrient status biomarkers were analyzed at baseline and late
      pregnancy. Children born to the women who participated in the trial were visited
      at 6-8 y of age. Fasting plasma glucose and insulin were used to estimate insulin
      resistance using the homeostasis model assessment (HOMA-IR). Children whose
      mothers were deficient in vitamin B-12 (<148 pmol/L, 27%) during early pregnancy
      had a 26.7% increase in HOMA-IR (P = 0.02), but there was no association with
      maternal folate status. Among children born to women who were vitamin B-12
      deficient at baseline, the percent difference in HOMA-IR compared to the control
      group was 15.1% (95% CI: -35.9, 106.4), 4.9% (-41.6, 88.5), 3.3% (-38.4, 73.5),
      and 18.1% (-29.0, 96.7) in the folic acid, folic acid-iron, folic acid-iron-zinc,
      and multiple micronutrient supplementation groups, respectively, none of which
      were significant. Maternal vitamin B-12 deficiency is associated with an elevated
      risk of insulin resistance, but supplementation with folic acid or other
      micronutrients led to no significant change in insulin resistance in school-aged
      offspring.

PMID- 21865564
TI  - Longitudinal change in diet quality in Australian adults varies by demographic,
      socio-economic, and lifestyle characteristics.
AB  - Knowledge of determinants of change in diet quality is needed, but it is
      relatively limited to date and mostly available from cross-sectional studies. We
      investigated longitudinal change in diet quality and its associations with period
      of birth (birth cohort) and socio-demographic and lifestyle characteristics. We
      used dietary intake data collected by FFQ in 1992, 1996, and 2007 from a
      population-based random sample of adults comprising 1511 men and women aged 25-75
      y at baseline and applied generalized estimating equations to examine
      determinants of long-term change in diet quality, calculated using a diet quality
      index reflecting dietary guidelines for Australian adults. Information on socio
      demographic and lifestyle factors was derived from self-reported questionnaires.
      Multivariable models, stratified by sex, were adjusted for confounders. We showed
      that there was an overall increase in diet quality in both men and women, but
      scores related to intake of fruit (men only), cereals, and food variety decreased
      during a 15-y follow-up. Younger age, higher occupational level (men only), and
      low to medium level of physical activity and hormone replacement therapy use in
      women were independently associated with greater improvement in diet quality over
      time (P < 0.05). In conclusion, despite an overall improvement in diet quality
      over time, this study suggests that efforts to further improve diet quality in
      Australia should focus on increasing consumption of fruit, cereals, and a greater
      variety of foods. More evidence from studies that assess change in dietary
      quality in longitudinal studies is needed to corroborate these findings.

PMID- 21865565
TI  - Maintenance energy requirements of growing pigs and calves are influenced by
      feeding level.
AB  - The conventional regression method for partitioning heat production (HP) in
      growing animals between HP associated with either maintenance or growth assumes
      maintenance HP to be independent of feeding level (FL). However, there are
      indications that this assumption is not correct and an alternative method is
      proposed in this study from a reanalysis of 3 trials. In trial 1, 73-, 152-, and
      237-kg calves received one milk replacer at 77, 84, 92, and 100% of their ad
      libitum metabolizable energy (ME) intake. In trial 2, 70-kg barrows received one
      diet at 60, 80, and 100% of their ad libitum ME intake {2600 kJ ME/[kg body
      weight (BW)(0.60) . d]}. In trial 3, 60-kg barrows received a basal diet [1700 kJ
      ME/(kg BW(0.60) . d)] or 4 diets consisting of the basal diet plus 850 kJ ME/(kg
      BW(0.60).d) of starch alone or starch with corn gluten, casein, or vegetable oil.
      In the 3 trials (n = 48, 18, and 28, respectively), HP and activity-related HP
      were measured on individuals pigs and calves in respiration chambers for 6 d (fed
      state) and fasting HP (FHP; at zero activity) was calculated as the asymptotic
      value of HP kinetics on d 7 (feed-deprived state). The FHP changed by 0.22 kJ in
      calves and 0.14 kJ in pigs/kJ ME intake change during the previous days. The
      efficiency of using ME for maintenance and growth [k(mg); 1- (HP - FHP)/ME] was
      not affected by FL (calves: 84%, pigs in trial 2: 74%). In trial 3, k(mg) varied
      between diets in connection with variations in efficiencies between nutrients
      (from 55% for corn gluten to 85% for lipid). This new method of representing
      partitioning of ME intake considers FHP as variable with FL, does not require
      estimates of maintenance ME requirements, includes efficiencies that depend on
      diet characteristics, and is not biased by metabolic adaptations of the animal to
      FL.

PMID- 21865566
TI  - Polyphenol-rich strawberry pomace reduces serum and liver lipids and alters
      gastrointestinal metabolite formation in fructose-fed rats.
AB  - This study compared the effects of supplementation with a polyphenol-rich pomace
      from strawberry (US) and a strawberry pomace without most of these compounds (PS)
      on gastrointestinal, blood, and tissue biomarkers in rats fed diets differing in
      carbohydrate contents for 4 wk. The diets were: corn starch (group CS), high
      fructose (60% by weight; group F), starch with 7.7% of either US or PS (groups
      CS+US and CS+PS, respectively), and high fructose with 7.7% of either US or PS
      (groups F+US and F+PS, respectively). An interaction (P < 0.05) was observed
      between diet type and strawberry preparation, showing that upon fructose feeding,
      US had a greater effect than PS on lowering serum insulin, liver total
      cholesterol, and conjugated dienes. Additionally, the F+US group had lower serum
      FFA than the F+PS group (P < 0.05). The extraction of polyphenols diminished the
      physiological effect associated with strawberry intake, suggesting that the fiber
      component of the pomace was also active in reducing metabolic complications
      following fructose feeding to rats.

PMID- 21865567
TI  - 20-Year trends in dietary and meal behaviors were similar in U.S. children and
      adolescents of different race/ethnicity.
AB  - Recent survey data reveal persistent race/ethnic disparities in prevalence of
      adiposity in U.S. children and adolescents. We examined race/ethnic differentials
      in time trends in dietary behaviors of Americans 2-19 y of age to understand if
      these trends track those observed for body weight. We used dietary data from the
      NHANES 1988-1994, 1999-2002, and 2003-2008 (n = 24,131) to examine changes in
      reported energy intake, amount of foods and beverages, number of eating
      occasions, and percent of energy from foods and beverages, among non-Hispanic
      white, non-Hispanic black, and Mexican American 2-19 y olds. Multivariable
      regression analyses appropriate for complex surveys were used to examine these
      associations. The secular increase in mean number of eating occasions was
      significant (P-trend < 0.0001) in all age and race/ethnic groups; however, a
      corresponding increase in the amount of foods and beverages, or total energy
      intake was not observed. In non-Hispanic black and Mexican American 2-5 and 12-19
      y olds, the secular increase in number of eating occasions, and in non-Hispanic
      black 12-19 y olds, the increase in percent of energy from all beverages or non
      nutritive beverages were greater relative to non-Hispanic whites. In conclusion,
      the observed race/ethnic differences in trajectory of changes in dietary
      behaviors over past 20 y were modest and were not accompanied by a significant
      increase in energy intake. Cautious interpretation is urged due to potential
      underreporting of dietary intake in national surveys. There was a suggestion of
      convergence in some race/ethnic differentials in dietary behaviors due to greater
      relative changes in possibly adverse behaviors in non-Hispanic blacks, especially
      adolescents.

PMID- 21865568
TI  - Foods, fortificants, and supplements: Where do Americans get their nutrients?
AB  - Limited data are available on the source of usual nutrient intakes in the United
      States. This analysis aimed to assess contributions of micronutrients to usual
      intakes derived from all sources (naturally occurring, fortified and enriched,
      and dietary supplements) and to compare usual intakes to the Dietary Reference
      Intake for U.S. residents aged >=2 y according to NHANES 2003-2006 (n = 16,110).
      We used the National Cancer Institute method to assess usual intakes of 19
      micronutrients by source. Only a small percentage of the population had total
      usual intakes (from dietary intakes and supplements) below the estimated average
      requirement (EAR) for the following: vitamin B-6 (8%), folate (8%), zinc (8%),
      thiamin, riboflavin, niacin, vitamin B-12, phosphorus, iron, copper, and selenium
      (<6% for all). However, more of the population had total usual intakes below the
      EAR for vitamins A, C, D, and E (34, 25, 70, and 60%, respectively), calcium
      (38%), and magnesium (45%). Only 3 and 35% had total usual intakes of potassium
      and vitamin K, respectively, greater than the adequate intake. Enrichment and/or
      fortification largely contributed to intakes of vitamins A, C, and D, thiamin,
      iron, and folate. Dietary supplements further reduced the percentage of the
      population consuming less than the EAR for all nutrients. The percentage of the
      population with total intakes greater than the tolerable upper intake level (UL)
      was very low for most nutrients, whereas 10.3 and 8.4% of the population had
      intakes greater than the UL for niacin and zinc, respectively. Without enrichment
      and/or fortification and supplementation, many Americans did not achieve the
      recommended micronutrient intake levels set forth in the Dietary Reference
      Intake.

PMID- 21865569
TI  - Increasing the vegetable intake dose is associated with a rise in plasma
      carotenoids without modifying oxidative stress or inflammation in overweight or
      obese postmenopausal women.
AB  - The optimal amount of vegetable consumption required to reduce chronic disease
      risk is widely debated. Intervention trials evaluating biological activity of
      vegetables at various doses are limited. We conducted a 3-dose, crossover feeding
      trial to test the hypothesis that vegetable intake is associated in a dose
      dependent manner with increased plasma carotenoids and subsequently reduced
      oxidative stress and inflammation in 49 overweight, postmenopausal women.
      Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614
      g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a
      4-wk washout period between treatments. Plasma total carotenoids significantly
      increased from 1.63 to 2.07 MUmol/L with a dose of 2 vegetable servings, from
      1.49 to 2.84 MUmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42
      MUmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P <
      0.001). The change during each feeding period increased with each dose level (P <
      0.001). Urine concentrations of 8-isoprostane F2alpha, hexanoyl lysine, and serum
      high sensitivity C-reactive protein were not affected by any administered
      vegetable dose. In this variable-dose vegetable study, a dose-response for plasma
      carotenoids was demonstrated without significant change in oxidative stress and
      inflammation in overweight, postmenopausal women.

PMID- 21865570
TI  - Acculturation factors are associated with folate intakes among Mexican American
      women.
AB  - Folic acid can prevent neural tube defects (NTD). Hispanic women have a higher
      prevalence of NTD than non-Hispanic white (NHW) women and consume less folic
      acid. Among Hispanics, acculturation has been associated with lower intakes of
      natural folate. It is unknown if this same relationship is seen for fortified
      foods. This article describes the associations of acculturation factors with
      usual folate intakes from foods and supplements and compares the proportion that
      meets recommended intakes of folic acid of US Mexican American (MA) women with
      those of NHW women. For US NHW and MA women aged 15-44 y (n = 3167), usual folate
      intakes (i.e., natural food folate, folic acid from food, total folic acid
      [fortified foods plus supplements], and total folate) were estimated using
      measurement error models from NHANES 2001-2008. Compared with NHW women, MA women
      did not differ in their intake of natural food folate or folic acid from food.
      Similarly, compared with NHW women (332 +/- 17.3 MUg/d), the mean total usual
      folic acid intakes were lower among MA women who reported speaking Spanish (224
      +/- 24.9 MUg/d) but not for MA women who reported speaking English (283 +/- 36.2
      MUg/d). MA women were more likely than NHW women to consume a total folic acid
      intake <400 MUg/d. MA women with lower acculturation factors were the most likely
      to have an intake <400 MUg/d compared to NHW women. Public health efforts should
      focus on increasing total folic acid intake among MA women, emphasizing those
      with lower acculturation factors (e.g., MA women who report speaking Spanish).

PMID- 21865571
TI  - Longitudinal assessment of oxaliplatin-induced neuropathy.
AB  - OBJECTIVES: To characterize the natural history of oxaliplatin-associated
      neuropathy (ON) and determine whether intraepidermal nerve fiber density (IENFD)
      is a sensitive measure of neuropathy progression. In addition, we sought to
      assess the potential of ON as a neuroprotection model and gain insight into the
      relationship between axon loss and neuropathic symptoms. METHODS: Eight subjects
      receiving oxaliplatin for advanced colorectal cancer were prospectively followed
      prior to starting chemotherapy and at 30, 90, 180, and 360 days (180 days after
      completing treatment). Electrophysiology, punch biopsies, symptom assessment, and
      examinations with calculation of a reduced total neuropathy score (rTNS) were
      performed at each time point. Changes over time were assessed through Poisson
      regression for IENFD and a mixed effects model for rTNS and electrophysiology
      measures. RESULTS: The distal leg IENFD, rTNS, peroneal, and sural amplitudes
      were all significantly reduced over time, while conduction velocity (peroneal and
      sural) and distal thigh IENFD were not. Measures of axon loss continued to worsen
      following discontinuation of oxaliplatin. Five of 8 subjects reported prominent
      symptoms associated with oxaliplatin administration. CONCLUSIONS: This study
      demonstrates that oxaliplatin is associated with mild, sensory, and motor axon
      loss that may not be reversible. Axonal loss was detected by electrophysiology,
      rTNS, and distal leg IENFD. Several subjects reported prominent sensory symptoms
      that were not associated with axon loss, and that may or may not represent
      neuropathy. ON is an attractive paradigm for neuroprotection studies and the
      distal leg IENFD is an objective measure that requires minimal subject
      participation or study site expertise.

PMID- 21865572
TI  - Acquiring new insights: incidence of acquired demyelination and MS in US
      children.

PMID- 21865573
TI  - Factors influencing in-hospital mortality and morbidity in patients treated on a
      stroke unit.
AB  - OBJECTIVE: To determine the extent that demographics, clinical characteristics,
      comorbidities, and complications contribute to the risk of in-hospital mortality
      and morbidity in acute stroke. METHODS: Data of consecutive patients admitted to
      14 stroke units cooperating within the Berlin Stroke Register were analyzed. The
      association of demographics, clinical characteristics, comorbidities, and
      complications with the risk of in-hospital death and poor outcome at discharge
      was assessed, and independent attributable risks were calculated, applying
      average sequential attributable fractions. RESULTS: In a 3-year period, 16,518
      consecutive patients with ischemic or hemorrhagic stroke were documented. In
      hospital mortality was 5.4%, and 45.7% had a poor outcome (modifed Rankin Scale
      score >=3). In patients with length of stay (LOS) <=7 days, 37.5% of in-hospital
      deaths were attributed to stroke severity, 23.1% to sociodemographics (age and
      prestroke disability), and 28.9% to increased intracranial pressure (iICP) and
      other complications. In those with LOS >7 days, age and stroke severity accounted
      for 44.1%, whereas pneumonia (12.2%), other complications (12.6%), and iICP
      (8.3%) contributed to one-third of in-hospital deaths. For poor outcome,
      attributable risks were similar for prestroke disability, stroke severity,
      pneumonia, and other complications regardless of the patient's LOS. CONCLUSIONS:
      Approximately two-thirds of early death and poor outcome in acute stroke is
      attributed to nonmodifiable predictors, whereas main modifiable factors are early
      complications such as iICP, pneumonia, or other complications, on which stroke
      unit treatment should focus to further improve the prognosis of acute stroke.

PMID- 21865574
TI  - Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and
      patients with lung cancer.
AB  - OBJECTIVE: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment
      for chemotherapy-induced peripheral neuropathy in an experimental animal model
      and in a randomized, double-blinded, controlled trial in patients with non-small
      cell lung cancer (NSCLC). METHODS: Forty male Wistar rats were randomized in 5
      groups: group A, control; groups B and C, treated with cisplatin; and groups D
      and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days
      in groups C and E. We evaluated neuropathy and nerve regeneration-related
      morphologic changes in sciatic nerve, the concentration of nerve growth factor
      (NGF), and retinoic acid receptor (RAR)-alpha and RAR-beta expression. In
      addition, 95 patients with NSCLC under chemotherapy treatment were randomized to
      either ATRA (20 mg/m(2)/d) or placebo. Serum NGF, neurophysiologic tests, and
      clinical neurotoxicity were assessed. RESULTS: The experimental animals developed
      neuropathy and axonal degeneration, associated with decreased NGF levels in
      peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve
      morphology; this was associated with increased NGF levels and RAR-beta
      expression. Patients treated with chemotherapy had clinical neuropathy and axonal
      loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA
      reduced axonal degeneration demonstrated by nerve conduction velocity and
      clinical manifestations of neuropathy grades >=2. CONCLUSIONS: ATRA reduced
      chemotherapy-induced experimental neuropathy, increased NGF levels, and induced
      RAR-beta expression in nerve. In patients, reduction of NGF in serum was
      associated with the severity of neuropathy; ATRA treatment reduced the
      electrophysiologic alterations. CLASSIFICATION OF EVIDENCE: This study provides
      Class II evidence that ATRA improves nerve conduction in patients with
      chemotherapy-induced peripheral neuropathy.

PMID- 21865575
TI  - Spectra to identify the spectre of Alzheimer disease?

PMID- 21865576
TI  - Early stroke risk: tissue is the issue.

PMID- 21865577
TI  - Magnetic resonance spectroscopy, beta-amyloid load, and cognition in a population
      based sample of cognitively normal older adults.
AB  - OBJECTIVE: To determine the relationship between proton magnetic resonance
      spectroscopy ((1)H MRS) metabolites and beta-amyloid (Abeta) load and the effects
      of Abeta load on the association between (1)H MRS metabolites and cognitive
      function in cognitively normal older adults. METHODS: We studied 311 cognitively
      normal older adults who participated in the population-based Mayo Clinic Study of
      Aging from January 2009 through September 2010. Participants underwent (11)C
      Pittsburgh compound B (PiB) PET, (1)H MRS from the posterior cingulate gyri, and
      neuropsychometric testing to assess memory, attention/executive, language, and
      visual-spatial domain functions within 6 months. Partial Spearman rank order
      correlations were adjusted for age, sex, and education. RESULTS: Higher PiB
      retention was associated with abnormal elevations in myoinositol (mI)/creatine
      (Cr) (partial r(s) = 0.17; p = 0.003) and choline (Cho)/Cr (partial r(s) = 0.13;
      p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on
      Auditory Verbal Learning Test Delayed Recall (partial r(s) = -0.12; p = 0.04),
      Trail Making Test Part B (partial r(s) = 0.12; p = 0.04), Wechsler Adult
      Intelligence Scale-Revised (WAIS-R) Digit Symbol (partial r(s) = -0.18; p <
      0.01), and WAIS-R Block Design (partial r(s) = -0.12; p = 0.03). Associations
      between (1)H MRS metabolites and cognitive function were not different among
      participants with high vs low PiB retention. CONCLUSION: In cognitively normal
      older adults, the (1)H MRS metabolite ratios mI/Cr and Cho/Cr are associated with
      the preclinical pathologic processes in the Alzheimer disease cascade. Higher
      Cho/Cr is associated with worse performance on domain-specific cognitive tests
      independent of Abeta load, suggesting that Cho/Cr elevation may also be dependent
      on other preclinical dementia pathologies characterized by Cho/Cr elevation such
      as Lewy body or ischemic vascular disease in addition to Abeta load.

PMID- 21865578
TI  - Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a
      multicenter study.
AB  - OBJECTIVES: Stroke risk immediately after TIA defined by time-based criteria is
      high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist
      management. The American Stroke Association has proposed changing the criteria
      for the distinction between TIA and stroke from time-based to tissue-based.
      Research using these definitions is lacking. In a multicenter observational
      cohort study, we have investigated prognosis and performance of the ABCD2 score
      in TIA, subcategorized as tissue-positive or tissue-negative on diffusion
      weighted imaging (DWI) or CT imaging according to the newly proposed criteria.
      METHODS: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging,
      and follow-up in cohorts of patients with TIA diagnosed by time-based criteria.
      Stroke rates at 7 and 90 days were studied in relation to tissue-positive or
      tissue-negative subcategorization, according to the presence or absence of brain
      infarction. The predictive power of the ABCD2 score was determined using area
      under receiver operator characteristic curve (AUC) analyses. RESULTS: A total of
      4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke
      rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive
      and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding
      rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2),
      respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue
      positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63
      0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff
      = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events
      with high ABCD2 scores had similar stroke risks, especially after a 90-day follow
      up. CONCLUSIONS: Our findings support the concept of a tissue-based definition of
      TIA and stroke, at least on prognostic grounds.

PMID- 21865579
TI  - Analysis of relapses in anti-NMDAR encephalitis.
AB  - OBJECTIVE: The clinical characteristics of patients with relapsing anti-NMDA
      receptor (NMDAR) encephalitis are not well-defined. In this study, we report the
      clinical profile and outcome of relapses in a series of anti-NMDAR encephalitis.
      METHODS: We did a retrospective review of relapses that occurred in 25 patients
      with anti-NMDAR encephalitis. Relapses were defined as any new psychiatric or
      neurologic syndrome, not explained by other causes, which improved after
      immunotherapy or, less frequently, spontaneously. RESULTS: A total of 13 relapses
      were identified in 6 patients. Four of them had several, 2 to 4, relapses. There
      was a median delay of 2 years (range 0.5 to 13 years) for the first relapse.
      Median relapse rate was 0.52 relapses/patient-year. Relapse risk was higher in
      patients who did not receive immunotherapy in the first episode (p = 0.009). Most
      cases (53%) presented partial syndromes of the typical anti-NMDAR encephalitis.
      Main symptoms of relapses were speech dysfunction (61%), psychiatric (54%),
      consciousness-attention disturbance (38%), and seizures (31%). Three relapses
      (23%) presented with isolated atypical symptoms suggestive of brainstem
      cerebellar involvement. An ovarian teratoma was detected at relapse in only 1
      patient (17%). Relapses did not add residual deficit to that caused by the first
      episode. CONCLUSIONS: Relapses in anti-NMDAR encephalitis are common (24%). They
      may occur many years after the initial episode. Relapses may present with partial
      aspects or with isolated symptoms of the full-blown syndrome. Immunotherapy at
      first episode reduces the risk of relapses.

PMID- 21865580
TI  - Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of
      children.
AB  - OBJECTIVE: To determine whether the incidence and clinical features of pediatric
      multiple sclerosis (MS) and other forms of pediatric acquired demyelinating
      syndromes (ADS) vary by race/ethnicity in a population-based cohort. METHODS: We
      used a combination of electronic database searches followed by complete medical
      records review to identify all children diagnosed with MS and ADS in the
      multiethnic membership of Kaiser Permanente Southern California from January 1,
      2004, to December 31, 2009. Incidence rates were standardized to the US census by
      age and gender. RESULTS: We identified 81 incident cases of ADS from 4.87 million
      person-years of observation in children 0-18 years of age. The incidence rate of
      pediatric MS was 0.51 per 100,000 person-years (95% confidence interval [CI] 0.33
      0.75) and incidence of other forms of ADS including optic neuritis, transverse
      myelitis, other forms of clinically isolated syndrome (CIS), and acute
      disseminated encephalomyelitis (ADEM) was 1.56 (95% CI 1.23-1.95) for an overall
      incidence of ADS of 1.66 per 100,000 person-years (95% CI 1.32-2.06). Incidence
      of ADS was higher in black (4.4 per 100,000 person-years, 95% CI 2.5-7.2, p <
      0.001) and Asian/Pacific Islander (2.8, 95% CI 1.2-5.2, p = 0.02) than white
      (1.03, 95% CI 0.6-1.7) and Hispanic (1.5, 95% CI 1.1-2.1, per 100,000 person
      years) children. Black children were also significantly more likely to have MS
      than white children (p = 0.001). Children who presented with ADEM were
      significantly younger than children with other types of ADS clinical
      presentations (mean age 5.6, range 0.7-17.6 years vs 14.6, range 2.7-18.5,
      respectively). CONCLUSIONS: The incidence of pediatric acquired demyelinating
      syndromes is 1.66 per 100,000 person-years in a population-based cohort of
      Southern Californian children. The incidence of ADS and MS is higher in black
      children compared with white and Hispanic children.

PMID- 21865581
TI  - Opsoclonus and multiple cranial neuropathy as a manifestation of
      neuroborreliosis.

PMID- 21865583
TI  - Growth factor regulation of neural chemorepellent Sema3A expression in satellite
      cell cultures.
AB  - Successful regeneration and remodeling of the intramuscular motoneuron network
      and neuromuscular connections are critical for restoring skeletal muscle function
      and physiological properties. The regulatory signals of such coordination remain
      unclear, although axon-guidance molecules may be involved. Recently, satellite
      cells, resident myogenic stem cells positioned beneath the basal lamina and at
      high density at the myoneural junction regions of mature fibers, were shown to
      upregulate a secreted neural chemorepellent semaphorin 3A (Sema3A) in response to
      in vivo muscle-crush injury. The initial report on that expression centered on
      the observation that hepatocyte growth factor (HGF), an essential cue in muscle
      fiber growth and regeneration, remarkably upregulates Sema3A expression in early
      differentiated satellite cells in vitro [Tatsumi et al., Am J Physiol Cell
      Physiol 297: C238-C252, 2009]. Here, we address regulatory effects of basic
      fibroblast growth factor (FGF2) and transforming growth factor (TGF)-betas on
      Sema3A expression in satellite cell cultures. When treated with FGF2, Sema3A
      message and protein were upregulated as revealed by reverse transcription
      polymerase chain reaction and immunochemical studies. Sema3A upregulation by FGF2
      was dose dependent with a maximum (8- to 1-fold relative to the control) at 2.5
      ng/ml (150 pM) and occurred exclusively at the early differentiation stage. The
      response was highly comparable in dose response and timing to effects of HGF
      treatment, without any additive or synergistic effect from treatment with a
      combination of both potent upregulators. In contrast, TGF-beta2 and -beta3
      potently decreased basal Sema3A expression; the maximum effect was at very low
      concentrations (40 and 8 pM, respectively) and completely cancelled the
      activities of FGF2 and HGF to upregulate Sema3A. These results therefore
      encourage the prospect that a time-coordinated increase in HGF, FGF2, and TGF
      beta ligands and their receptors promotes a programmed strategy for Sema3A
      expression that guarantees successful intramuscular motor reinnervation by
      delaying sprouting and reattachment of motoneuron terminals onto damaged muscle
      fibers early in regeneration pending restoration of muscle fiber contractile
      integrity.

PMID- 21865582
TI  - Genetic deletion of trkB.T1 increases neuromuscular function.
AB  - Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL
      modulates neuromuscular synapse maintenance and function; however, it is unclear
      what role the alternative splice variant, truncated trkB (trkB.T1), may have in
      the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice
      and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle
      tension are significantly increased. In vitro assays indicated that the gain-in
      function in trkB.T1(-/-) animals resulted specifically from an increased muscle
      contractility, and increased electrically evoked calcium release. In the trkB.T1
      null muscle, we identified an increase in Akt activation in resting muscle as
      well as a significant increase in trkB.FL and Akt activation in response to
      contractile activity. On the basis of these findings, we conclude that the trkB
      signaling pathway might represent a novel target for intervention across diseases
      characterized by deficits in neuromuscular function.

PMID- 21865584
TI  - G protein-coupled estrogen receptor 1-mediated effects in the rat myometrium.
AB  - G protein-coupled estrogen receptor 1 (GPER), also named GPR30, has been
      previously identified in the female reproductive system. In this study, GPER
      expression was found in the female rat myometrium by reverse transcriptase
      polymerase chain reaction and immunocytochemistry. Using GPER-selective ligands,
      we assessed the effects of the GPER activation on resting membrane potential and
      cytosolic Ca(2+) concentration ([Ca(2+)](i)) in rat myometrial cells, as well as
      on contractility of rat uterine strips. G-1, a specific GPER agonist, induced a
      concentration-dependent depolarization and increase in [Ca(2+)](i) in myometrial
      cells. The depolarization was abolished in Na(+)-free saline. G-1-induced
      [Ca(2+)](i) increase was markedly decreased by nifedipine, a L-type Ca(2+)
      channel blocker, by Ca(2+)-free or Na(+)-free saline. Intracellular
      administration of G-1 produced a faster and transitory increase in [Ca(2+)](i),
      with a higher amplitude than that induced by extracellular application,
      supporting an intracellular localization of the functional GPER in myometrial
      cells. Depletion of internal Ca(2+) stores with thapsigargin produced a robust
      store-activated Ca(2+) entry; the Ca(2+) response to G-1 was similar to the
      constitutive Ca(2+) entry and did not seem to involve store-operated Ca(2+)
      entry. In rat uterine strips, administration of G-1 increased the frequency and
      amplitude of contractions and the area under the contractility curve. The effects
      of G-1 on membrane potential, [Ca(2+)](i), and uterine contractility were
      prevented by pretreatment with G-15, a GPER antagonist, further supporting the
      involvement of GPER in these responses. Taken together, our results indicate that
      GPER is expressed and functional in rat myometrium. GPER activation produces
      depolarization, elevates [Ca(2+)](i) and increases contractility in myometrial
      cells.

PMID- 21865585
TI  - Truncated IRAG variants modulate cGMP-mediated inhibition of human colonic smooth
      muscle cell contraction.
AB  - Nitric oxide (NO) induces relaxation of colonic smooth muscle cells predominantly
      by cGMP/cGMP-dependent protein kinase I (cGKI)-induced phosphorylation of the
      inositol 1,4,5-trisphosphate receptor (IP(3)R)-associated cGMP kinase substrate
      (IRAG), to block store-dependent calcium signaling. In the present study we
      analyzed the structure and function of the human IRAG/MRVI1 gene. We describe
      four unique first exon variants transcribed from individual promoters in diverse
      human tissues. Tissue-specific alternative splicing with exon skipping and
      alternative splice donor and acceptor site usage further increases diversity of
      IRAG mRNA variants that encode for NH(2)- and COOH-terminally truncated proteins.
      At the functional level, COOH-terminally truncated IRAG variants lacking both the
      cGKI phosphorylation and the IP(3)RI interaction site counteract cGMP-mediated
      inhibition of calcium transients and relaxation of human colonic smooth muscle
      cells. Since COOH-terminally truncated IRAG mRNA isoforms are widely expressed in
      human tissues, our results point to an important role of IRAG variants as
      negative modulators of nitric oxide/cGKI-dependent signaling. The complexity of
      alternative splicing of the IRAG gene impressively demonstrates how
      posttranscriptional processing generates functionally distinct proteins from a
      single gene.

PMID- 21865586
TI  - Tissue length modulates "stimulated actin polymerization," force augmentation,
      and the rate of swine carotid arterial contraction.
AB  - "Stimulated actin polymerization" has been proposed to be involved in force
      augmentation, in which prior submaximal activation of vascular smooth muscle
      increases the force of a subsequent maximal contraction by ~15%. In this study,
      we altered stimulated actin polymerization by adjusting tissue length and then
      measured the effect on force augmentation. At optimal tissue length (1.0 L(o)),
      force augmentation was observed and was associated with increased prior
      stimulated actin polymerization, as evidenced by increased prior Y118 paxillin
      phosphorylation without changes in prior S3 cofilin or cross-bridge
      phosphorylation. Tissue length, per se, regulated Y118 paxillin, but not S3
      cofilin, phosphorylation. At short tissue length (0.6 L(o)), force augmentation
      was observed and was associated with increased prior stimulated actin
      polymerization, as evidenced by reduced prior S3 cofilin phosphorylation without
      changes in Y118 paxillin or cross-bridge phosphorylation. At long tissue length
      (1.4 L(o)), force augmentation was not observed, and there were no prior changes
      in Y118 paxillin, S3 cofilin, or cross-bridge phosphorylation. There were no
      significant differences in the cross-bridge phosphorylation transients before and
      after the force augmentation protocol at all three lengths tested. Tissues
      contracted faster at longer tissue lengths; contractile rate correlated with
      prior Y118 paxillin phosphorylation. Total stress, per se, predicted Y118
      paxillin phosphorylation. These data suggest that force augmentation is regulated
      by stimulated actin polymerization and that stimulated actin polymerization is
      regulated by total arterial stress. We suggest that K(+) depolarization first
      leads to cross-bridge phosphorylation and contraction, and the contraction
      induced increase in mechanical strain increases Y118 paxillin phosphorylation,
      leading to stimulated actin polymerization, which further increases force, i.e.,
      force augmentation and, possibly, latch.

PMID- 21865587
TI  - Hypoxic culture and in vivo inflammatory environments affect the assumption of
      pericyte characteristics by human adipose and bone marrow progenitor cells.
AB  - Previous studies have shown that exposure to a hypoxic in vitro environment
      increases the secretion of pro-angiogenic growth factors by human adipose-derived
      stromal cells (hASCs) [Cao Y, et al., Biochem Biophys Res Commun 332: 370-379,
      2005; Kokai LE, et al., Plast Reconstr Surg 116: 1453-1460, 2005; Park BS, et
      al., Biomed Res (Tokyo) 31: 27-34, 2010; Rasmussen JG, et al., Cytotherapy 13:
      318-328, 2010; Rehman J, et al., Circulation 109: 1292-1298, 2004]. Previously,
      it has been demonstrated that hASCs can differentiate into pericytes and promote
      microvascular stability and maintenance during angiogenesis in vivo (Amos PJ, et
      al., Stem Cells 26: 2682-2690, 2008; Traktuev DO, et al., Circ Res 102: 77-85,
      2008). In this study, we tested the hypotheses that angiogenic induction can be
      increased and pericyte differentiation decreased by pretreatment of hASCs with
      hypoxic culture and that hASCs are similar to human bone marrow-derived stromal
      cells (hBMSCs) in these regards. Our data confirms previous studies showing that
      hASCs: 1) secrete pro-angiogenic proteins, which are upregulated following
      culture in hypoxia, and 2) migrate up gradients of PDGF-BB in vitro, while
      showing for the first time that a rat mesenteric model of angiogenesis induced by
      48/80 increases the propensity of both hASCs and hBMSCs to assume perivascular
      phenotypes following injection. Moreover, culture of both cell types in hypoxia
      before injection results in a biphasic vascular length density response in this
      model of inflammation-induced angiogenesis. The effects of hypoxia and
      inflammation on the phenotype of adult progenitor cells impacts both the
      therapeutic and the basic science applications of the cell types, as hypoxia and
      inflammation are common features of natural and pathological vascular
      compartments in vivo.

PMID- 21865589
TI  - Mast cells function as an alternative modulator of adipogenesis through 15-deoxy
      delta-12, 14-prostaglandin J2.
AB  - Mast cells are one of the major producers of prostaglandins (PGs). The final
      metabolite of PGs 15-deoxy-delta-12,14-PGJ(2) (15-deoxy-delta PGJ(2)) is the
      endogenous ligand of the peroxisome proliferator-activated receptor (PPAR) gamma.
      PPARgamma modulates adipocyte differentiation; therefore, we attempted to
      investigate whether PGs derived from mast cells influenced on adipogenesis. We
      found the increase of mast cell numbers in fat tissue of obese mice fed with a
      high-fat diet allowed us to speculate contributions of mast cells to
      adipogenesis. Mast cell-mediated induction of adipogenesis was evaluated by using
      3T3 L1 cells. Supernatants obtained from mast cells stimulated with calcium
      ionophore or the high-glucose condition contained 15-deoxy-delta PGJ(2) and
      induced adipogenesis of 3T3 L1 cells. Agonistic activity of PGJ(2) from the
      supernatants on PPARgamma was confirmed by a reporter gene assay. Culture medium
      collected from calcium ionophore-stimulated bone marrow-derived cultured mast
      cells (BMCMC) activated PPAR-responsive element in NIH3T3 fibroblasts, and the
      specific inhibitor of PPARgamma canceled the activation. Contribution of mast
      cells to obesity was evaluated by using mast cell-deficient mice fed with a
      Western diet. Weight gain of mast cell-deficient mice during high-fat feeding was
      impaired compared with their littermate wild-type mice; on the other hand,
      transplantation of bone marrow-derived cultured mast cells to mast cell-deficient
      mice restored the weight gain by intake of a high-fat diet. In this study, we
      clearly demonstrated that mast cells produced PGs in response to the high-glucose
      condition and induced adipocyte differentiation and possibly obesity. This is the
      first study that provides evidence for a novel role of mast cells in adipogenesis
      via PPARgamma activation.

PMID- 21865588
TI  - A calcineurin homologous protein is required for sodium-proton exchange events in
      the C. elegans intestine.
AB  - Caenorhabditis elegans defecation is a rhythmic behavior, composed of three
      sequential muscle contractions, with a 50-s periodicity. The motor program is
      driven by oscillatory calcium signaling in the intestine. Proton fluxes, which
      require sodium-proton exchangers at the apical and basolateral intestinal
      membranes, parallel the intestinal calcium flux. These proton shifts are critical
      for defecation-associated muscle contraction, nutrient uptake, and longevity. How
      sodium-proton exchangers are activated in time with intestinal calcium
      oscillation is not known. The posterior body defecation contraction mutant (pbo
      1) encodes a calcium-binding protein with homology to calcineurin homologous
      proteins, which are putative cofactors for mammalian sodium-proton exchangers.
      Loss of pbo-1 function results in a weakened defecation muscle contraction and a
      caloric restriction phenotype. Both of these phenotypes also arise from
      dysfunctions in pH regulation due to mutations in intestinal sodium-proton
      exchangers. Dynamic, in vivo imaging of intestinal proton flux in pbo-1 mutants
      using genetically encoded pH biosensors demonstrates that proton movements
      associated with these sodium-proton exchangers are significantly reduced. The
      basolateral acidification that signals the first defecation motor contraction is
      scant in the mutant compared with a normal animal. Luminal and cytoplasmic pH
      shifts are much reduced in the absence of PBO-1 compared with control animals. We
      conclude that pbo-1 is required for normal sodium-proton exchanger activity and
      may couple calcium and proton signaling events.

PMID- 21865590
TI  - No muscle atrophy without GSK-3beta. Focus on "Glycogen synthase kinase-3beta is
      required for the induction of skeletal muscle atrophy".

PMID- 21865591
TI  - Expression and possible immune-regulatory function of ghrelin in oral epithelium.
AB  - Originally found in stomach mucosa, ghrelin is a peptide appetite hormone that
      has been implicated as an immuno-modulatory factor. Ghrelin has also been found
      in salivary glands and saliva; however, its expression patterns and biological
      properties in the oral cavity remain unclear. Therefore, we investigated the
      expression patterns of ghrelin in saliva, gingival crevicular fluid (GCF), and
      gingival tissue, as well as its in vitro effects on IL-8 production by TNF-alpha
      or LPS-stimulated oral epithelial cells. In the clinical samples obtained from 12
      healthy volunteers, the concentration of ghrelin in GCF remarkably exceeded that
      detected in saliva. The expression of ghrelin mRNAs and growth hormone
      secretagogue (GHS) receptors could be detected in human oral epithelial cells.
      Immunohistochemical analysis revealed the expression of ghrelin in gingival
      epithelium, as well as in fibroblasts in the lamina propria. Ghrelin increased
      intracellular calcium mobilization and cAMP levels in oral epithelial cells,
      suggesting that ghrelin acts on epithelial cells to induce cell signaling.
      Furthermore, synthetic ghrelin inhibited the production of IL-8 from TNF-alpha or
      LPS-stimulated oral epithelial cells. These results indicate that ghrelin
      produced in the oral cavity appears to play a regulatory role in innate immune
      responses to inflammatory infection.

PMID- 21865592
TI  - Double edge: CDK2AP1 in cell-cycle regulation and epigenetic regulation.
AB  - Cancer research has been devoted toward an understanding of the molecular
      regulation and functional significance of cell-cycle regulators in the
      pathogenesis and development of cancers. Cyclin-dependent Kinase 2-associated
      Protein 1 (CDK2AP1) is one such cell-cycle regulator, originally identified as a
      growth suppressor and a prognostic marker for human oral/head and neck cancers.
      Functional importance and the molecular mechanism of CDK2AP1-mediated cell-cycle
      regulation have been documented over the years. Recent progress has shown that
      CDK2AP1 is a competency factor in embryonic stem cell differentiation. Deletion
      of CDK2AP1 leads to early embryonic lethality, potentially through altered
      differentiation capability of embryonic stem cells. More intriguingly, CDK2AP1
      exerts its effect on stem cell maintenance/differentiation through epigenetic
      regulation. Cancer cells and stem cells share common cellular characteristics,
      most prominently in maintaining high proliferative potential through an
      unconventional cell-cycle regulatory mechanism. Cross-talk between cellular
      processes and molecular signaling pathways is frequent in any biological system.
      Currently, it remains largely elusive how cell-cycle regulation is
      mechanistically linked to epigenetic control. Understanding the molecular
      mechanism underlying CDK2AP1-mediated cell-cycle regulation and epigenetic
      control will set an example for establishing a novel and effective molecular link
      between these two important regulatory mechanisms.

PMID- 21865593
TI  - Ligand activation leads to regulated intramembrane proteolysis of fibroblast
      growth factor receptor 3.
AB  - Fibroblast growth factor receptor 3 (FGFR3) is a major negative regulator of bone
      growth that inhibits the proliferation and differentiation of growth plate
      chondrocytes. Activating mutations of its c isoform cause dwarfism in humans;
      somatic mutations can drive oncogenic transformation in multiple myeloma and
      bladder cancer. How these distinct activities arise is not clear. FGFR3 was
      previously shown to undergo proteolytic cleavage in the bovine rib growth plate,
      but this was not explored further. Here, we show that FGF1 induces regulated
      intramembrane proteolysis (RIP) of FGFR3. The ectodomain is proteolytically
      cleaved (S1) in response to ligand-induced receptor activation, but unlike most
      RIP target proteins, it requires endocytosis and does not involve a
      metalloproteinase. S1 cleavage generates a C-terminal domain fragment that
      initially remains anchored in the membrane, is phosphorylated, and is spatially
      distinct from the intact receptor. Ectodomain cleavage is followed by
      intramembrane cleavage (S2) to generate a soluble intracellular domain that is
      released into the cytosol and can translocate to the nucleus. We identify the S1
      cleavage site and show that gamma-secretase mediates the S2 cleavage event. In
      this way we demonstrate a mechanism for the nuclear localization of FGFR3 in
      response to ligand activation, which may occur in both development and disease.

PMID- 21865594
TI  - Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its
      distribution between mitochondria and the cytosol.
AB  - Superoxide dismutase 1 (Sod1) is an important antioxidative enzyme that converts
      superoxide anions to hydrogen peroxide and water. Active Sod1 is a homodimer
      containing one zinc ion, one copper ion, and one disulfide bond per subunit.
      Maturation of Sod1 depends on its copper chaperone (Ccs1). Sod1 and Ccs1 are
      dually localized proteins that reside in the cytosol and in the intermembrane
      space of mitochondria. The import of Ccs1 into mitochondria depends on the
      mitochondrial disulfide relay system. However, the exact mechanism of this import
      process has been unclear. In this study we detail the import and folding pathway
      of Ccs1 and characterize its interaction with the oxidoreductase of the
      mitochondrial disulfide relay Mia40. We identify cysteines at positions 27 and 64
      in domain I of Ccs1 as critical for mitochondrial import and interaction with
      Mia40. On interaction with Mia40, these cysteines form a structural disulfide
      bond that stabilizes the overall fold of domain I. Although the cysteines are
      essential for the accumulation of functional Ccs1 in mitochondria, they are
      dispensable for the enzymatic activity of cytosolic Ccs1. We propose a model in
      which the Mia40-mediated oxidative folding of domain I controls the cellular
      distribution of Ccs1 and, consequently, active Sod1.

PMID- 21865595
TI  - ARHGAP18, a GTPase-activating protein for RhoA, controls cell shape, spreading,
      and motility.
AB  - Rho GTPases are molecular switches that transmit biochemical signals in response
      to extracellular stimuli to elicit changes in the actin cytoskeleton. Rho GTPases
      cycle between an active, GTP-bound state and an inactive, GDP-bound state. These
      states are regulated by two distinct families of proteins-guanine nucleotide
      exchange factors and GTPase-activating proteins (GAPs). We studied the role of a
      previously uncharacterized GAP, ARHGAP18 (MacGAP). Overexpression of ARHGAP18
      suppressed the activity of RhoA and disrupted stress fiber formation. Conversely,
      silencing of ARHGAP18 by small interfering RNA transfection-enhanced stress fiber
      formation and induced rounding of cells. We examined the role of ARHGAP18 in cell
      spreading and migration. Immunofluorescence analysis revealed that ARHGAP18 was
      localized to the leading edge during cell spreading and migration. ARHGAP18
      knockdown cells showed impaired spreading, premature formation of stress fibers,
      and sustained activation of RhoA upon cell attachment. In addition, knockdown and
      overexpression of ARHGAP18 resulted in the inhibition and promotion of cell
      migration, respectively. Furthermore, ARHGAP18 was required for the polarization
      of cells for migration. Our results define ARHGAP18 as one of the crucial factors
      for the regulation of RhoA for the control of cell shape, spreading, and
      migration.

PMID- 21865596
TI  - Prevention of estradiol 17beta-D-glucuronide-induced canalicular transporter
      internalization by hormonal modulation of cAMP in rat hepatocytes.
AB  - In estradiol 17beta-d-glucuronide (E17G)-induced cholestasis, the canalicular
      hepatocellular transporters bile salt export pump (Abcb11) and multidrug
      resistance associated protein 2 (Abcc2) undergo endocytic internalization. cAMP
      stimulates the trafficking of transporter-containing vesicles to the apical
      membrane and is able to prevent internalization of these transporters in estrogen
      induced cholestasis. Hepatocyte levels of cAMP are regulated by hormones such as
      glucagon and adrenaline (via the beta2 receptor). We analyzed the effects of
      glucagon and salbutamol (a beta2 adrenergic agonist) on function and localization
      of Abcb11 and Abcc2 in isolated rat hepatocyte couplets exposed to E17G and
      compared the mechanistic bases of their effects. Glucagon and salbutamol
      partially prevented the impairment in Abcb11 and Abcc2 transport capacity. E17G
      also induced endocytic internalization of Abcb11 and Abcc2, which partially
      colocalized with the endosomal marker Rab11a. This effect was completely
      prevented by salbutamol, whereas some transporter-containing vesicles remained
      internalized and mainly colocalizing with Rab11a in the perinuclear region after
      incubation with glucagon. Glucagon prevention was dependent on cAMP-dependent
      protein kinase (PKA) and independent of exchange proteins activated directly by
      cAMP (Epac) and microtubules. In contrast, salbutamol prevention was PKA
      independent and Epac/MEK and microtubule dependent. Anticholestatic effects of
      glucagon and salbutamol were additive in nature. Our results show that increases
      in cAMP could activate different anticholestatic signaling pathways, depending on
      the hormonal mediator involved.

PMID- 21865597
TI  - Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute
      activation of Na+/H+ exchanger NHE3 by glucocorticoids.
AB  - Na(+)/H(+) exchanger 3 (NHE3) is the major Na(+) transporter in the intestine.
      Serum- and glucocorticoid-induced kinase (SGK) 1 interacts with NHE regulatory
      factor 2 (NHERF2) and mediates activation of NHE3 by dexamethasone (Dex) in
      cultured epithelial cells. In this study, we compared short-term regulation of
      NHE3 by Dex in SGK1-null and NHERF2-null mice. In comparison to wild-type mice,
      loss of SGK1 or NHERF2 significantly attenuated regulation of NHE3 by Dex but did
      not completely obliterate the effect. We show that transfection of SGK2 or SGK3
      in PS120 cells resulted in robust activation of NHE3 by Dex. However, unlike SGK1
      or SGK2, SGK3 rapidly activated NHE3 within 15 min of Dex treatment in both PS120
      and Caco-2bbe cells. Immunofluorescence analysis showed that SGK3 colocalized
      with NHE3 in recycling endosomes, whereas SGK1 and SGK2 were diffusely
      distributed. Mutation of Arg-90 of SGK3 disrupted the endosomal localization of
      SGK3 and delayed NHE3 activation. Activation of SGK3 and NHE3 by Dex was
      dependent on phosphoinositide 3-kinase (PI3K) and phosphoinositide-dependent
      kinase 1 (PDK1), and Dex induced translocation of PDK1 to endosomes. Our study
      identifies SGK3 as a novel endosomal kinase that acutely regulates NHE3 in a PI3K
      dependent mechanism.

PMID- 21865598
TI  - The functionally distinct fission yeast formins have specific actin-assembly
      properties.
AB  - Fission yeast expresses three formins required for distinct actin cytoskeletal
      processes: Cdc12 (cytokinesis), For3 (polarization), and Fus1 (mating). We
      propose that in addition to differential regulation, key actin-assembly
      properties tailor formins for a particular role. In direct comparison to the well
      studied Cdc12, we report the first in vitro characterization of the actin
      assembly properties of For3 and Fus1. All three share fundamental formin
      activities; however, particular reaction rates vary significantly. Cdc12 is an
      efficient nucleator (one filament per approximately 3 Cdc12 dimers) that
      processively elongates profilin-actin at a moderate rate of 10 subunits s(-1)
      MUM(-1), but lacks filament-bundling activity. Fus1 is also an efficient
      nucleator, yet processively elongates profilin-actin at one-half the rate of and
      dissociates 10-fold more rapidly than Cdc12; it also bundles filaments. For3
      nucleates filaments 100-fold less well than Fus1, but like Cdc12, processively
      elongates profilin-actin at a moderate rate and lacks filament-bundling activity.
      Additionally, both the formin homology FH1 and FH2 domains contribute to the
      overall rate of profilin-actin elongation. We also confirmed the physiological
      importance of the actin-assembly activity of the fission yeast formins. Point
      mutants that disrupt their ability to stimulate actin assembly in vitro do not
      function properly in vivo.

PMID- 21865599
TI  - The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix
      proteins are essential for endothelial cell lumen formation.
AB  - A role for fibroblasts in physiological and pathological angiogenesis is now well
      recognized; however, the precise mechanisms underlying their action have not been
      determined. Using an in vitro angiogenesis model in combination with a candidate
      gene approach, column chromatography, and mass spectrometry, we identify two
      classes of fibroblast-derived factors--one that supports vessel sprouting but not
      lumen formation, and one that promotes lumen formation. In the absence of
      fibroblasts a combination of angiopoietin-1, angiogenin, hepatocyte growth
      factor, transforming growth factor-alpha, and tumor necrosis factor drives robust
      endothelial cell (EC) sprouting; however, lumens fail to form. Subsequent
      addition of fibroblast-conditioned medium restores lumenogenesis. Using small
      interfering RNA-mediated knockdown, we show that five genes expressed in
      fibroblasts--collagen I, procollagen C endopeptidase enhancer 1, secreted protein
      acidic and rich in cysteine, transforming growth factor-beta-induced protein ig
      h3, and insulin growth factor-binding protein 7--are necessary for lumen
      formation. Moreover, lumen formation can be rescued by addition of purified
      protein to knockdown cultures. Finally, using rheology, we demonstrate that the
      presence of these matricellular proteins results in significantly stiffer gels,
      which correlates with enhanced lumen formation. These findings highlight the
      critical role that fibroblast-derived extracellular matrix components play in EC
      lumen formation and provide potential insight into the role of fibroblasts in the
      tumor microenvironment.

PMID- 21865600
TI  - Knock-in reconstitution studies reveal an unexpected role of Cys-65 in regulating
      APE1/Ref-1 subcellular trafficking and function.
AB  - Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1) protects cells from
      oxidative stress via the base excision repair pathway and as a redox
      transcriptional coactivator. It is required for tumor progression/metastasis, and
      its up-regulation is associated with cancer resistance. Loss of APE1 expression
      causes cell growth arrest, mitochondrial impairment, apoptosis, and alterations
      of the intracellular redox state and cytoskeletal structure. A detailed knowledge
      of the molecular mechanisms regulating its different activities is required to
      understand the APE1 function associated with cancer development and for targeting
      this protein in cancer therapy. To dissect these activities, we performed
      reconstitution experiments by using wild-type and various APE1 mutants. Our
      results suggest that the redox function is responsible for cell proliferation
      through the involvement of Cys-65 in mediating APE1 localization within
      mitochondria. C65S behaves as a loss-of-function mutation by affecting the in
      vivo folding of the protein and by causing a reduced accumulation in the
      intermembrane space of mitochondria, where the import protein Mia40 specifically
      interacts with APE1. Treatment of cells with (E)-3-(2-[5,6-dimethoxy-3-methyl-1,4
      benzoquinonyl])-2-nonyl propenoic acid, a specific inhibitor of APE1 redox
      function through increased Cys-65 oxidation, confirm that Cys-65 controls APE1
      subcellular trafficking and provides the basis for a new role for this residue.

PMID- 21865601
TI  - Mitochondrial Ccs1 contains a structural disulfide bond crucial for the import of
      this unconventional substrate by the disulfide relay system.
AB  - The copper chaperone for superoxide dismutase 1 (Ccs1) provides an important
      cellular function against oxidative stress. Ccs1 is present in the cytosol and in
      the intermembrane space (IMS) of mitochondria. Its import into the IMS depends on
      the Mia40/Erv1 disulfide relay system, although Ccs1 is, in contrast to typical
      substrates, a multidomain protein and lacks twin Cx(n)C motifs. We report on the
      molecular mechanism of the mitochondrial import of Saccharomyces cerevisiae Ccs1
      as the first member of a novel class of unconventional substrates of the
      disulfide relay system. We show that the mitochondrial form of Ccs1 contains a
      stable disulfide bond between cysteine residues C27 and C64. In the absence of
      these cysteines, the levels of Ccs1 and Sod1 in mitochondria are strongly
      reduced. Furthermore, C64 of Ccs1 is required for formation of a Ccs1 disulfide
      intermediate with Mia40. We conclude that the Mia40/Erv1 disulfide relay system
      introduces a structural disulfide bond in Ccs1 between the cysteine residues C27
      and C64, thereby promoting mitochondrial import of this unconventional substrate.
      Thus the disulfide relay system is able to form, in addition to double disulfide
      bonds in twin Cx(n)C motifs, single structural disulfide bonds in complex protein
      domains.

PMID- 21865602
TI  - Role of Survivin in cytokinesis revealed by a separation-of-function allele.
AB  - The chromosomal passenger complex (CPC), containing Aurora B kinase, Inner
      Centromere Protein, Survivin, and Borealin, regulates chromosome condensation and
      interaction between kinetochores and microtubules at metaphase, then relocalizes
      to midzone microtubules at anaphase and regulates central spindle organization
      and cytokinesis. However, the precise role(s) played by the CPC in anaphase have
      been obscured by its prior functions in metaphase. Here we identify a missense
      allele of Drosophila Survivin that allows CPC localization and function during
      metaphase but not cytokinesis. Analysis of mutant cells showed that Survivin is
      essential to target the CPC and the mitotic kinesin-like protein 1 orthologue
      Pavarotti (Pav) to the central spindle and equatorial cell cortex during anaphase
      in both larval neuroblasts and spermatocytes. Survivin also enabled localization
      of Polo kinase and Rho at the equatorial cortex in spermatocytes, critical for
      contractile ring assembly. In neuroblasts, in contrast, Survivin function was not
      required for localization of Rho, Polo, or Myosin II to a broad equatorial
      cortical band but was required for Myosin II to transition to a compact, fully
      constricted ring. Analysis of this "separation-of-function" allele demonstrates
      the direct role of Survivin and the CPC in cytokinesis and highlights striking
      differences in regulation of cytokinesis in different cell systems.

PMID- 21865603
TI  - Identification and experimental validation of splicing regulatory elements in
      Drosophila melanogaster reveals functionally conserved splicing enhancers in
      metazoans.
AB  - RNA sequence elements involved in the regulation of pre-mRNA splicing have
      previously been identified in vertebrate genomes by computational methods. Here,
      we apply such approaches to predict splicing regulatory elements in Drosophila
      melanogaster and compare them with elements previously found in the human, mouse,
      and pufferfish genomes. We identified 99 putative exonic splicing enhancers
      (ESEs) and 231 putative intronic splicing enhancers (ISEs) enriched near weak 5'
      and 3' splice sites of constitutively spliced introns, distinguishing between
      those found near short and long introns. We found that a significant proportion
      (58%) of fly enhancer sequences were previously reported in at least one of the
      vertebrates. Furthermore, 20% of putative fly ESEs were previously identified as
      ESEs in human, mouse, and pufferfish; while only two fly ISEs, CTCTCT and TTATAA,
      were identified as ISEs in all three vertebrate species. Several putative
      enhancer sequences are similar to characterized binding-site motifs for
      Drosophila and mammalian splicing regulators. To provide additional evidence for
      the function of putative ISEs, we separately identified 298 intronic hexamers
      significantly enriched within sequences phylogenetically conserved among 15
      insect species. We found that 73 putative ISEs were among those enriched in
      conserved regions of the D. melanogaster genome. The functions of nine enhancer
      sequences were verified in a heterologous splicing reporter, demonstrating that
      these sequences are sufficient to enhance splicing in vivo. Taken together, these
      data identify a set of predicted positive-acting splicing regulatory motifs in
      the Drosophila genome and reveal regulatory sequences that are present in distant
      metazoan genomes.

PMID- 21865604
TI  - Preliminary Evidence of Significant Gaps in Continuity of HIV Care among
      Excarcerated Populations in Puerto Rico.
AB  - OBJECTIVE: Puerto Rico has high HIV prevalence and incidence rates, including a
      large prison population living with HIV. While HIV treatment is available within
      the prisons, there are no linkages to care or treatment preparedness
      interventions following release. METHODS: In an effort to assess the risk of
      treatment discontinuity in this group, we examined data from an ongoing
      epidemiological study in the largest, publicly funded HIV/sexually transmitted
      infection (STI) treatment center in the San Juan area. RESULTS: Among the newly
      enrolled, HIV-positive patients with a history of incarceration, there was an
      average 4-year gap in reengagement in treatment. Drug and sexual risk behaviors
      were prevalent, as was evidence of significant immune impairment (including high
      viral load and low CD4 count). CONCLUSIONS: Treatment discontinuity may
      contribute to poor health outcomes in this group and also fuel new infections.
      There is an urgent need for interventions to retain HIV-positive inmates in
      community HIV care following release.

PMID- 21865606
TI  - Stems to GEMs: impact of stem cell technology on engineered animal models.
AB  - Collectively, these presentations introduced the audience to the roles of ES
      cells in generating phenotypes of transgenic animals,and they provided examples
      where the GEMs were used to define molecular mechanisms of disease or where ES
      cells were used as a therapeutic modality. Points of discussion among audience
      members reinforced the importance of strain-associated background lesions in
      animal models, technological advances in imaging functional biology,
      opportunities for stem cell therapies, and ubiquitination in regulation of cell
      proliferation. The 2012 American College of Veterinary Pathologists symposium
      ''Evolutionary Aspects of Animal Models'' will focus on the proper selection of a
      relevant animal model in biomedical research as critical to investigative
      success. Recent work characterizing rapid evolutionary changes and differences in
      physiology between species questions the validity of some comparative models. Dr.
      Robert Hamlin will be speaking on cardiovascular disease in ''Animals as Models
      of Human Cardiovascular Disease: Or the Search to Overcome Outdated Evolutionary
      Homeostatic Mechanisms.'' Dr. Stefan Niewiesk will discuss evolutionary factors
      that affect modeling the human immune system in ''Of Mice and Men:
      Evolutionarily, What Are the Best Rodent Models of the Human Immune System for
      Infectious Disease Research?'' Dr. Steven Austad will consider evolution in
      ''Evolutionary Aspects of Animal Models of Aging.''Finally, Dr. Elizabeth Uhl
      will conclude the session with ''Modeling Disease Phenotypes: How an Evolutionary
      Perspective Enhances the Questions.''

PMID- 21865607
TI  - Heterogeneity of cancer patient information-seeking behaviors.
AB  - OBJECTIVES: This study aimed to determine whether cancer patients report
      different information-seeking behaviors (ISBs), investigate why they searched for
      information, and determine the relationship between their ISBs and their
      socioeconomic and behavioral characteristics. The authors also explored the
      relationship between ISB and participation in the medical decision-making process
      as well as the patients' health state. METHODS: A sample of 4270 French cancer
      survivors aged 18 or older was interviewed at 2 years following diagnosis. Rather
      than deciding a priori who should be considered an information seeker, the
      authors chose to statistically define the different ISBs using cluster analysis.
      RESULTS: The authors identified 4 distinct profiles: Stereotypical high
      information seekers and acquainted seekers are generally highly educated. They
      search for information due to their own motivation or because they are close to
      the medical profession. Constrained information seekers are characterized by a
      low socioeconomic status. They perceive themselves as "dropouts" of the health
      care system. Finally, the general information seekers did not systematically
      resort to any specific ISB. The authors show that after adjustment, belonging to
      a specific ISB was associated with the likelihood of participating in the medical
      decision-making process and, more surprisingly, with health state. CONCLUSIONS: A
      key finding of this study is that social disparities are significantly associated
      with the different ISBs. If these relationships are found in other samples, it
      would further support the need for medical teams to pay more attention to
      patients with lower levels of education, particularly in health care systems that
      have acknowledged equality as a founding principle. The clusters determined in
      this study offer a potential theoretical framework that can be used in future
      studies.

PMID- 21865608
TI  - Prevalence of owner-reported behaviours in dogs separated from the litter at two
      different ages.
AB  - The present study examined the prevalence of behaviours in dogs separated from
      the litter for adoption at different ages. Seventy adult dogs separated from
      their dam and littermates and adopted between the ages of 30 and 40 days were
      compared with 70 adult dogs that had been taken from the litter for adoption at
      two months. Owners were asked to complete a questionnaire eliciting information
      on whether their dog exhibited potentially problematic behaviours when in its
      usual environment. Binary logistic regression analysis was performed to
      investigate whether the age at which the dog was separated from the litter might
      predispose it to developing undesirable behaviours. The odds of displaying
      destructiveness, excessive barking, fearfulness on walks, reactivity to noises,
      toy possessiveness, food possessiveness and attention-seeking were significantly
      greater for the dogs that had been removed from the litter earlier during the
      socialisation period. In addition, dogs purchased from a pet shop at 30 to 40
      days of age were reported to exhibit some of the listed behaviours with a
      significantly higher frequency than dogs purchased from a pet shop at two months.
      No significant differences were observed with dogs obtained from other types of
      sources. The dogs in the youngest age group (18 to 36 months) had a higher
      probability of displaying destructiveness and tail chasing. These findings
      indicate that, compared with dogs that remained with their social group for 60
      days, dogs that had been separated from the litter earlier were more likely to
      exhibit potentially problematic behaviours, especially if they came from a pet
      shop.

PMID- 21865609
TI  - Aurora kinase inhibition overcomes cetuximab resistance in squamous cell cancer
      of the head and neck.
AB  - Squamous cell cancer of the head and neck (SCCHN) is the sixth leading cause for
      cancer deaths worldwide. Despite extense knowledge of risk factors and
      pathogenesis about 50 percent of all patients and essentially every patient with
      metastatic SCCHN eventually die from this disease. We analyzed the clinical data
      and performed immunohistochemistry for Epidermal growth factor receptor (EGFR)
      and Aurora kinase A (Aurora-A) expression in 180 SCCHN patients. Patients
      characterized by elevated EGFR and elevated Aurora-A protein expression in tumor
      tissue represent a risk group with poor disease-free and overall survival
      (EGFR(low)Aurora-A(low) versus EGFR(high)Aurora-A(high), p = 0.024). Treating
      SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective
      cytokinesis, polyploidy and apoptosis, which was effective irrespective of the
      EGFR status. Combined Aurora kinase and EGFR targeting using a monoclonal anti
      EGFR antibody was more effective compared to single EGFR and Aurora kinase
      inhibition. Comparing pan-Aurora kinase and Aurora-A targeting hints towards a
      strong and clinically relevant biological effect mediated via Aurora kinase B.
      Taken together, our findings characterize a new poor risk group in SCCHN patients
      defined by elevated EGFR and Aurora-A protein expression. Our results demonstrate
      that combined targeting of EGFR and Aurora kinases represents a therapeutic means
      to activate cell cycle checkpoints and apoptosis in SCCHN.

PMID- 21865611
TI  - Doses to the red bone marrow of young people and adults from radiation of natural
      origin.
AB  - Natural radiation sources comprise cosmic rays, terrestrial gamma rays,
      radionuclides in food and inhaled isotopes of radon with their decay products.
      These deliver doses to all organs and tissues including red bone marrow (RBM),
      the tissue in which leukaemia is thought to originate. In this paper we calculate
      the age-dependent annual RBM doses from natural radiation sources to young people
      and to adults at average levels of exposure in the UK. The contributions to dose
      are generally less complex than in the case of doses to foetuses and young
      children where it is necessary to take into account transfer of radionuclides
      across the placenta, intakes in mother's milk and changes in gut uptake in young
      infants. However, there is high uptake of alkaline earths and of similar elements
      in the developing skeleton and this significantly affects the doses from
      radioisotopes of these elements, not just in the teens and twenties but through
      into the fifth decade of life. The total equivalent dose to the RBM from all
      natural sources of radiation at age 15 years is calculated to be about 1200  uSv
      a year at average UK levels, falling to rather less than 1100  uSv per year in
      later life; the gentle fall from the late teens onwards reflects the diminishing
      effect of the high uptakes of radioisotopes of the alkaline earths and of lead in
      this period. About 60% of the equivalent dose is contributed by the low linear
      energy transfer (LET) component. Radionuclides in food make the largest
      contribution to equivalent doses to RBM and much the largest contribution to the
      absorbed dose from high LET radiation (mainly alpha particles).

PMID- 21865610
TI  - PaCATB, a secreted catalase protecting Podospora anserina against exogenous
      oxidative stress.
AB  - A differential mass spectrometry analysis of secreted proteins from juvenile and
      senescent Podospora anserina cultures revealed age-related differences in protein
      profiles. Among other proteins with decreased abundance in the secretome of
      senescent cultures a catalase, termed PaCATB, was identified. Genetic modulation
      of the abundance of PaCATB identified differential effects on the phenotype of
      the corresponding strains. Deletion of PaCatB resulted in decreased resistance,
      over-expression in increased resistance against hydrogen peroxide. While the
      lifespan of the genetically modified strains was found to be unaffected under
      standard growth conditions, increased exogenous hydrogen peroxide stress in the
      growth medium markedly reduced the lifespan of the PaCatB deletion strain but
      extended the lifespan of PaCatB over-expressors. Overall our data identify a
      component of the secretome of P. anserina as a new effective factor to cope with
      environmental stress, stress that under natural conditions is constantly applied
      on organisms and influences aging processes.

PMID- 21865612
TI  - Radioactive waste policy and legislation: 50 years on from the 1960 Act.
AB  - Over the past 50 years a comprehensive regulatory framework for radioactive
      substances in the UK has been progressively introduced, important initial
      milestones being the white paper Cmnd 884 and the Radioactive Substances Act
      1960. During the 1970s and 1980s there were a succession of enquiries and white
      papers which developed from the growing awareness of the problems of the nuclear
      waste legacy. This was followed by a comprehensive policy white paper in 1995: Cm
      2919. In 1990, 1993, 1995 and 2005 some aspects of the 1960 Act were updated. The
      most recent, and most radical, modernisation took place in 2010, when the Act was
      incorporated into the Environmental Permitting Regulations, in England and Wales.
      Currently a major review of the exemption orders and exclusion criteria under the
      radioactive substances legislation is close to completion, which will complete
      the current phase of modernisation of the regulatory framework.

PMID- 21865613
TI  - A German storm affecting Britain: childhood leukaemia and nuclear power plants.

PMID- 21865614
TI  - Measurement of radon concentration for assessment of the radiological hazard in
      the Chakwal coalmines of the Salt Range, Pakistan.
AB  - Radon and its progeny are prevalent everywhere on the lithosphere especially in
      the mining environment. Coal exists in the Salt Range that passes through
      Pakistan. The aim of the present study was to measure radon concentration and
      assess the associated radiological hazard in the coalmines developed in that
      portion of the Salt Range which passes through the district of Chakwal in
      Pakistan. Among the various coalmines in the coalfield, five were selected for
      radon survey. A passive integrated technique consisting of SSNTDs (solid state
      nuclear track detectors) was employed for the measurement of radon concentration
      in these coalmines. Box type dosimeters containing CN-85 detectors were placed
      for three months at six locations in every selected coalmine. After removing the
      dosimeters, the CN-85 detectors were etched in alkaline solution to enlarge the
      alpha tracks in the detectors and counted under an optical microscope. The track
      densities were converted to radon concentration. The average concentration of
      radon in the coalmines varied in the range 50-114  Bq m(-3). Radon exhalation
      rates from the samples of coal and shale collected from the coalmines were
      determined to be respectively 934 (830-1010) and 1302 (1020-1580)  mBq m(-2) h(
      1). The radiation dose and corresponding health risk for the mine workers were
      also estimated.

PMID- 21865616
TI  - Investigation of the environmental impacts of naturally occurring radionuclides
      in the processing of sulfide ores for gold using gamma spectrometry.
AB  - The possible environmental impacts of naturally occurring radionuclides on
      workers and a critical community, as a result of milling and processing sulfide
      ores for gold by a mining company at Bogoso in the western region of Ghana, have
      been investigated using gamma spectroscopy. Indicative doses for the workers
      during sulfide ore processing were calculated from the activity concentrations
      measured at both physical and chemical processing stages. The dose rate, annual
      effective dose equivalent, radium equivalent activity, external and internal
      hazard indices, and radioactivity level index for tailings, for the de-silted
      sediments of run-off from the vicinity of the tailings dam through the critical
      community, and for the soils of the critical community's basic schools were
      calculated and found to be lower than their respective permissible limits. The
      environmental impact of the radionuclides is therefore expected to be low in this
      mining environment.

PMID- 21865617
TI  - Radiation risks and radiation protection training for healthcare professionals:
      ICRP and the Fukushima experience.

PMID- 21865618
TI  - The use of volunteer radon measurements for radon mapping purposes: an
      examination of sampling bias issues.
AB  - National and regional radon surveys are used in many nations to produce maps
      detailing the spatial variation of indoor radon concentrations. National surveys
      which are designed to be representative use either a geographically-weighted or a
      population-weighted sampling scheme. Additionally, many countries collect a large
      number of data on indoor radon concentrations from volunteers who have chosen to
      have the indoor radon concentration measured in their own dwellings. This work
      examines the representativeness of volunteer-based samples in radon measurement
      and explores the effect of potential volunteer bias on radon mapping results. We
      also investigate the influence that media attention has on volunteer sampling of
      indoor radon concentrations. The result of our work indicates that volunteer
      measurements are biased due to over-sampling of high radon areas. Consequently
      such volunteer radon measurements should not be used for radon mapping purposes.

PMID- 21865619
TI  - Risks from ionising radiation: an HPA viewpoint paper for Safegrounds.
AB  - Safegrounds is a forum for developing and disseminating good practice guidance on
      the management of radioactively contaminated land on nuclear and defence sites in
      the UK. This review has been provided to Safegrounds as a summary of the basis
      for current radiation risk estimates and the International Commission on
      Radiological Protection (ICRP) protection system, in a form that will be
      accessible to a wide range of stakeholders. Safegrounds has also received
      viewpoint papers from other members who contend that the ICRP methodology results
      in substantial underestimates of risk, particularly for internal emitters. There
      is an extensive literature on the risks of radiation exposure, regularly reviewed
      by the United Nations Scientific Committee on the Effects of Atomic Radiation
      (UNSCEAR) and other expert groups. These data provide a sound basis for the
      system of protection recommended by ICRP. The available epidemiological and
      experimental evidence supports the application of cancer risk estimates derived
      for acute, high dose, external exposures to low dose exposures to external and
      internal sources. In the context of radioactively contaminated land on nuclear
      and defence sites, the national standards for the cleaning up of land and for
      waste disposal correspond to very low doses, two orders of magnitude less than
      average annual doses in the UK from natural background radiation (10-20  uSv
      compared with 2-3 mSv). Risks at such very low doses can only be estimated on the
      basis of observations after exposure of population groups at much higher doses.
      The estimated risks at these very low doses, while uncertain, are as likely to be
      overestimates as underestimates.

PMID- 21865620
TI  - Toward the modeling of mucus draining from the human lung: role of the geometry
      of the airway tree.
AB  - Mucociliary clearance and cough are the two main natural mucus draining methods
      in the bronchial tree. If they are affected by a pathology, they can become
      insufficient or even ineffective, then therapeutic draining of mucus plays a
      critical role to keep mucus levels in the lungs acceptable. The manipulations of
      physical therapists are known to be very efficient clinically but they are mostly
      empirical since the biophysical mechanisms involved in these manipulations have
      never been studied. We develop in this work a model of mucus clearance in
      idealized rigid human bronchial trees and focus our study on the interaction
      between (1) tree geometry, (2) mucus physical properties and (3) amplitude of
      flow rate in the tree. The mucus is considered as a Bingham fluid (gel-like)
      which is moved upward in the tree thanks to its viscous interaction with air
      flow. Our studies point out the important roles played both by the geometry and
      by the physical properties of mucus (yield stress and viscosity). More
      particularly, the yield stress has to be overcome to make mucus flow. Air flow
      rate and yield stress determine the maximal possible mucus thickness in each
      branch of the tree at equilibrium. This forms a specific distribution of mucus in
      the tree whose characteristics are strongly related to the multi-scaled structure
      of the tree. The behavior of any mucus distribution is then dependent on this
      distribution. Finally, our results indicate that increasing air flow rates ought
      to be more efficient to drain mucus out of the bronchial tree while minimizing
      patient discomfort.

PMID- 21865621
TI  - The effects of 7-dehydrocholesterol on the structural properties of membranes.
AB  - Smith-Lemli-Opitz syndrome, a congenital and developmental malformation disease,
      is typified by abnormal accumulation of 7-dehydrocholesterol (7DHC), the
      immediate precursor of cholesterol (CHOL), and depletion thereof. Knowledge of
      the effect of 7DHC on the biological membrane is, however, still fragmentary. In
      this study, large-scale atomistic molecular dynamics simulations, employing two
      distinct force fields, have been conducted to elucidate differences in the
      structural properties of a hydrated dimyristoylphosphatidylcholine bilayer due to
      CHOL and 7DHC. The present series of results indicate that CHOL and 7DHC possess
      virtually the same ability to condense and order membranes. Furthermore, the
      condensing and ordering effects are shown to be strengthened at increasing sterol
      concentrations.

PMID- 21865622
TI  - Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang
      attenuation correction.
AB  - Attenuation of photon flux on trajectories between the source and pinhole
      apertures affects the quantitative accuracy of reconstructed single-photon
      emission computed tomography (SPECT) images. We propose a Chang-based non-uniform
      attenuation correction (NUA-CT) for small-animal SPECT/CT with focusing pinhole
      collimation, and compare the quantitative accuracy with uniform Chang correction
      based on (i) body outlines extracted from x-ray CT (UA-CT) and (ii) on hand drawn
      body contours on the images obtained with three integrated optical cameras (UA
      BC). Measurements in phantoms and rats containing known activities of isotopes
      were conducted for evaluation. In (125)I, (201)Tl, (99m)Tc and (111)In phantom
      experiments, average relative errors comparing to the gold standards measured in
      a dose calibrator were reduced to 5.5%, 6.8%, 4.9% and 2.8%, respectively, with
      NUA-CT. In animal studies, these errors were 2.1%, 3.3%, 2.0% and 2.0%,
      respectively. Differences in accuracy on average between results of NUA-CT, UA-CT
      and UA-BC were less than 2.3% in phantom studies and 3.1% in animal studies
      except for (125)I (3.6% and 5.1%, respectively). All methods tested provide
      reasonable attenuation correction and result in high quantitative accuracy. NUA
      CT shows superior accuracy except for (125)I, where other factors may have more
      impact on the quantitative accuracy than the selected attenuation correction.

PMID- 21865623
TI  - Semi-quantitative and simulation analyses of effects of gamma rays on
      determination of calibration factors of PET scanners with point-like (22)Na
      sources.
AB  - The uncertainty of radioactivity concentrations measured with positron emission
      tomography (PET) scanners ultimately depends on the uncertainty of the
      calibration factors. A new practical calibration scheme using point-like (22)Na
      radioactive sources has been developed. The purpose of this study is to
      theoretically investigate the effects of the associated 1.275 MeV gamma rays on
      the calibration factors. The physical processes affecting the coincidence data
      were categorized in order to derive approximate semi-quantitative formulae.
      Assuming the design parameters of some typical commercial PET scanners, the
      effects of the gamma rays as relative deviations in the calibration factors were
      evaluated by semi-quantitative formulae and a Monte Carlo simulation. The
      relative deviations in the calibration factors were less than 4%, depending on
      the details of the PET scanners. The event losses due to rejecting multiple
      coincidence events of scattered gamma rays had the strongest effect. The results
      from the semi-quantitative formulae and the Monte Carlo simulation were
      consistent and were useful in understanding the underlying mechanisms. The
      deviations are considered small enough to correct on the basis of precise Monte
      Carlo simulation. This study thus offers an important theoretical basis for the
      validity of the calibration method using point-like (22)Na radioactive sources.

PMID- 21865624
TI  - On a PCA-based lung motion model.
AB  - Respiration-induced organ motion is one of the major uncertainties in lung cancer
      radiotherapy and is crucial to be able to accurately model the lung motion. Most
      work so far has focused on the study of the motion of a single point (usually the
      tumor center of mass), and much less work has been done to model the motion of
      the entire lung. Inspired by the work of Zhang et al (2007 Med. Phys. 34 4772
      81), we believe that the spatiotemporal relationship of the entire lung motion
      can be accurately modeled based on principle component analysis (PCA) and then a
      sparse subset of the entire lung, such as an implanted marker, can be used to
      drive the motion of the entire lung (including the tumor). The goal of this work
      is twofold. First, we aim to understand the underlying reason why PCA is
      effective for modeling lung motion and find the optimal number of PCA
      coefficients for accurate lung motion modeling. We attempt to address the above
      important problems both in a theoretical framework and in the context of real
      clinical data. Second, we propose a new method to derive the entire lung motion
      using a single internal marker based on the PCA model. The main results of this
      work are as follows. We derived an important property which reveals the implicit
      regularization imposed by the PCA model. We then studied the model using two
      mathematical respiratory phantoms and 11 clinical 4DCT scans for eight lung
      cancer patients. For the mathematical phantoms with cosine and an even power (2n)
      of cosine motion, we proved that 2 and 2n PCA coefficients and eigenvectors will
      completely represent the lung motion, respectively. Moreover, for the cosine
      phantom, we derived the equivalence conditions for the PCA motion model and the
      physiological 5D lung motion model (Low et al 2005 Int. J. Radiat. Oncol. Biol.
      Phys. 63 921-9). For the clinical 4DCT data, we demonstrated the modeling power
      and generalization performance of the PCA model. The average 3D modeling error
      using PCA was within 1 mm (0.7 +/- 0.1 mm). When a single artificial internal
      marker was used to derive the lung motion, the average 3D error was found to be
      within 2 mm (1.8 +/- 0.3 mm) through comprehensive statistical analysis. The
      optimal number of PCA coefficients needs to be determined on a patient-by-patient
      basis and two PCA coefficients seem to be sufficient for accurate modeling of the
      lung motion for most patients. In conclusion, we have presented thorough
      theoretical analysis and clinical validation of the PCA lung motion model. The
      feasibility of deriving the entire lung motion using a single marker has also
      been demonstrated on clinical data using a simulation approach.

PMID- 21865626
TI  - Failings of the International Nuclear Event Scale at Fukushima: the citizen's
      perspective.

PMID- 21865625
TI  - Verdicts on radiofrequency electromagnetic fields from IARC and ICNIRP. Verifying
      Canadian nuclear energy worker radiation risk: a reanalysis of cancer mortality
      in Canadian nuclear energy workers (1957-1994). Childhood cancer in the vicinity
      of nuclear power plants: results of the CANUPIS study. Environment Agencies'
      statement on Radioactive Waste Advisers and associated guidance. BBC Trust-BBC
      science coverage given 'vote of confidence' by independent report.

PMID- 21865627
TI  - A modified blade element theory for estimation of forces generated by a beetle
      mimicking flapping wing system.
AB  - We present an unsteady blade element theory (BET) model to estimate the
      aerodynamic forces produced by a freely flying beetle and a beetle-mimicking
      flapping wing system. Added mass and rotational forces are included to
      accommodate the unsteady force. In addition to the aerodynamic forces needed to
      accurately estimate the time history of the forces, the inertial forces of the
      wings are also calculated. All of the force components are considered based on
      the full three-dimensional (3D) motion of the wing. The result obtained by the
      present BET model is validated with the data which were presented in a reference
      paper. The difference between the averages of the estimated forces (lift and
      drag) and the measured forces in the reference is about 5.7%. The BET model is
      also used to estimate the force produced by a freely flying beetle and a beetle
      mimicking flapping wing system. The wing kinematics used in the BET calculation
      of a real beetle and the flapping wing system are captured using high-speed
      cameras. The results show that the average estimated vertical force of the beetle
      is reasonably close to the weight of the beetle, and the average estimated thrust
      of the beetle-mimicking flapping wing system is in good agreement with the
      measured value. Our results show that the unsteady lift and drag coefficients
      measured by Dickinson et al are still useful for relatively higher Reynolds
      number cases, and the proposed BET can be a good way to estimate the force
      produced by a flapping wing system.

PMID- 21865628
TI  - p-n homo-junction arrays of aligned single walled carbon nanotubes fabricated by
      selective patterning of polyethyleneimine film.
AB  - We describe the fabrication and electrical performance of p-n homo-junction diode
      arrays of horizontally aligned single walled carbon nanotubes (SWCNTs).
      Horizontally aligned SWCNTs grown on stable temperature-cut quartz with a density
      of ~ 6 SWCNTs um(-1) were transferred onto a SiO(2)/Si substrate. After the
      electrical breakdown, aligned SWCNT field effect transistors (FETs) showed
      unipolar p-type characteristics with a large current on/off ratio of 10(6) at 1 V
      and a hole mobility per tube of 1500 cm(2) V(-1) s(-1). Spin-coating of
      polyethyleneimine (PEI) onto p-type SWCNT FETs showed the n-type transfer
      characteristics. Patterning of spin-coated PEI film enabled the fabrication of p
      n homo-junction arrays of aligned SWCNTs in an easy way, where the rectifying
      behavior was observed with a rectification ratio of ~ 10(4) at +/- 2 V. A
      comparative study with a p-n homo-junction of random networks of SWCNTs confirmed
      the advantage of aligned SWCNTs for applications in high performance electronic
      devices.

PMID- 21865630
TI  - Multi-parametric growth of silicon nanowires in a single platform by laser
      induced localized heat sources.
AB  - Nanoscale-synthesized materials hold great promise for the realization of future
      generation devices. In order to fulfil this exceptional promise, new techniques
      must be developed that will enable the precise layout and assembly of the
      heterogeneous components into functional 'superblocks'. Direct synthesis of
      nanostructures via a laser-assisted chemical vapor deposition process is one
      promising route. In this paper, laser-assisted silicon nanowire growth based on a
      vapor-liquid-solid (VLS) mechanism is studied. Spatial confinement of the
      nanowire growth region via focused laser beam illumination provides a convenient
      way to examine multiple growth parameters (temperature, time, illumination
      direction, gas species composition, and pressure), thereby elucidating
      fundamental mechanisms of laser-assisted growth in a single sample configuration.
      Furthermore, the work demonstrates an advanced method for direct synthesis of
      nanostructures for the purpose of practical rapid patterning.

PMID- 21865629
TI  - Dynamic properties of spin cluster glass and the exchange bias effect in BiFeO3
      nanocrystals.
AB  - A spin cluster glass behavior and a complicated exchange bias effect are observed
      in high quality BiFeO(3) nanocrystals grown by a hydrothermal method. The dynamic
      properties of the spin clusters investigated by measuring the frequency
      dependences of ac susceptibility show that the relaxation process can be
      described using a power law with the glass transition temperature T(g) = 57 K,
      relaxation time constant tau(0) = 4.4 * 10(-10) s, and critical exponent zv =
      10.3 +/- 1.9, consistent with a three-dimensional Ising spin glass. The exchange
      bias field (H(EB)) varies non-monotonically with temperature and achieves a
      minimum at T(g). The abnormal shift of hysteresis loops above T(g) may be
      interpreted in terms of a Malozemoff's random-field model with a framework of
      antiferromagnetic core/spin-cluster shell structure and a two-dimensional diluted
      antiferromagnet in a field (2D-DAFF) model, respectively. The exchange anisotropy
      of the BiFeO(3) nanocrystals will shed light on a possible application for
      magnetism related nanosized devices.

PMID- 21865631
TI  - Characterization of individual barium titanate nanorods and their assessment as
      building blocks of new circuit architectures.
AB  - In this work, we report on the integration of individual BaTiO(3) nanorods into
      simple circuit architectures. Polycrystalline BaTiO(3) nanorods were synthesized
      by electrophoretic deposition (EPD) of barium titanate sol into aluminium oxide
      (AAO) templates and subsequent annealing. Transmission electron microscopy (TEM)
      observations revealed the presence of slabs of hexagonal polymorphs intergrown
      within cubic grains, resulting from the local reducing atmosphere during the
      thermal treatment. Electrical measurements performed on individual BaTiO(3)
      nanorods revealed resistivity values between 10 and 100 Omega cm, which is in
      good agreement with typical values reported in the past for oxygen-deficient
      barium titanate films. Consequently the presence of oxygen vacancies in their
      structure was indirectly validated. Some of these nanorods were tested as proof
      of-concept humidity sensors. They showed reproducible responses towards different
      moisture concentrations, demonstrating that individual BaTiO(3) nanorods may be
      integrated in complex circuit architectures with functional capacities.

PMID- 21865632
TI  - Fabrication and characterization of bit-patterned media beyond 1.5 Tbit/in2.
AB  - We fabricated bit-patterned media (BPM) at densities as high as 3.3 Tbit/in(2)
      using a process consisting of high-resolution electron-beam lithography followed
      directly by magnetic film deposition. By avoiding pattern transfer processes such
      as etching and liftoff that inherently reduce pattern fidelity, the resolution of
      the final pattern was kept close to that of the lithographic step. Magnetic force
      microscopy (MFM) showed magnetic isolation of the patterned bits at 1.9
      Tbit/in(2), which was close to the resolution limit of the MFM. The method
      presented will enable studies on magnetic bits packed at ultra-high densities,
      and can be combined with other scalable patterning methods such as templated self
      assembly and nanoimprint lithography for high-volume manufacturing.

PMID- 21865633
TI  - Boroxol rings from diffraction data on vitreous boron trioxide.
AB  - There has been a considerable debate about the nature of the short range atomic
      order in vitreous B(2)O(3). Some authorities state that it is not possible to
      build a model of glassy boron oxide of the correct density containing a large
      number of six-membered rings which also fits experimental diffraction data, but
      recent computer simulations appear to overrule that view. To discover which view
      is correct I use empirical potential structure refinement (EPSR) on existing
      neutron and x-ray diffraction data to build two models of vitreous B(2)O(3). One
      of these consists only of single boron and oxygen atoms arranged in a network to
      reproduce the diffraction data as closely as possible. This model has less than
      10% of boron atoms in boroxol rings. The second model is made up of an equimolar
      mixture of B(3)O(3) hexagonal ring 'molecules' and BO(3) triangular molecules,
      with no free boron or oxygen atoms. This second model therefore has 75% of the
      boron atoms in boroxol rings. It is found that both models give closely similar
      diffraction patterns, suggesting that the diffraction data in this case are not
      sensitive to the number of boroxol rings present in the structure. This
      reinforces recent Raman, ab initio, and NMR claims that the percentage of boroxol
      rings in this material may be as high as 75%. The findings of this study probably
      explain why some interpretations based on different simulation techniques only
      find a small fraction of boroxol rings. The results also highlight the power of
      EPSR for the extraction of accurate atomistic representations of amorphous
      structures, provided adequate additional, non-scattering data (such as Raman and
      NMR in this case) are available.

PMID- 21865634
TI  - Electronic structure and trilayer growth of indium films on Si(111): a
      photoemission study.
AB  - We report on the preferred trilayer growth of indium films on Si(111) studied by
      angle-resolved photoemission spectroscopy. By employing an interfactant and
      optimized annealing conditions, the kinetic constraint on the In atoms due to the
      substrate is greatly reduced and 'electronic growth'-where film morphology is
      controlled by the quantized electronic structure of the film-can be achieved at
      low coverage. Our photoemission spectra reveal that films of 4 ML (monolayers)
      and 7 ML thicknesses are energetically favored due to a lower surface energy, as
      confirmed by theoretical calculations. A detailed comparison of the photoemission
      spectra between In films grown on the In-?3 * ?3/Si(111) surface and those on the
      Si(111) 7 * 7 surface shows that the ?3 * ?3 interfactant is a better template
      for growing In films at low coverage and effectively reduces the electronic
      coupling between the film and the substrate. In addition, the observed band
      structures of In films are in reasonable agreement with first-principles
      calculations and suggest that In films grown on the ?3 * ?3 interfactant might
      already be close to the bulk-like body-centered tetragonal structure at around 10
      ML.

PMID- 21865635
TI  - Structural phase transitions in EuFe2As2 superconductor at low temperatures and
      high pressures.
AB  - The crystal structure of EuFe(2)As(2) has been studied up to a pressure of 35 GPa
      and down to a temperature of 8 K using temperature dependent x-ray diffraction in
      a diamond anvil cell at a synchrotron source. At 4.3 GPa, we have detected a
      structural phase transition from a high temperature tetragonal phase with I4/mmm
      space group to a low temperature orthorhombic phase with Fmmm space group around
      120 K. With the application of pressure at a low temperature of 10 K, the
      orthorhombic phase is suppressed and a phase change to a collapsed tetragonal
      phase with I4/mmm space group is observed at 11 GPa. This collapsed tetragonal
      phase is similar to the one observed at ambient temperature and pressure above
      8.5 GPa. We have shown that the collapsed tetragonal phase of EuFe(2)As(2) has
      the same pressure-volume (P-V) equation of state at ambient temperature and at 10
      K, implying that the high pressure phase of EuFe(2)As(2) has a negligible thermal
      expansion coefficient.

PMID- 21865636
TI  - Interplay between charge stripes and sign reversals of Hall and Seebeck effects
      in stripe-ordered La(1.6-x)Nd0.4Sr(x)CuO4 superconductors.
AB  - The Hall and Seebeck effects of the stripe-ordered superconductor La(1.6
      x)Nd(0.4)Sr(x)CuO(4) single crystals (x = 0.10, 0.12 and 0.15) were investigated
      systematically. The sign change of Hall and Seebeck coefficients (R(H) and S)
      from positive to negative with decreasing temperature suggests the presence of
      electron pockets in the Fermi surface due to the stripe ordering. We successfully
      tune this behavior through an epitaxial strain induced by the mismatch between
      the thin film and the substrate. The negative R(H) disappears in the thinner film
      in which the static charge stripe is greatly suppressed by the strong epitaxial
      strain, and for a strain released thicker film the negative R(H) recovers. These
      results indicate the possibility of Fermi surface reconstruction caused by the
      static charge stripe order in the system.

PMID- 21865637
TI  - Understanding the spin glass transition as a dynamic phenomenon.
AB  - Existing theories explain the spin glass transition in terms of a phase
      transition and order parameters, and assume the existence of a distinct spin
      glass phase. In addition to problems related to clarifying the nature of this
      phase, the common challenge is to explain profound dynamic effects. Here, we
      propose that the main experimental results of the spin glass transition can be
      understood in an entirely dynamic picture, without a reference to a distinct spin
      glass phase, phase transition and order parameters. In this theory, the
      susceptibility cusp at the glass transition temperature is due to the dynamic
      crossover between the high-temperature relaxational and low-temperature spin wave
      regimes. The crossover takes place when t = tau, where t is the observation time
      and tau is the relaxation time. Time-dependent effects, inconsistent with the
      phase transition approach, and the logarithmic increase of T(g) with field
      frequency in particular, originate as the immediate consequence of the proposed
      picture. In our discussion, we explore similarities between the spin and
      structural glass transitions.

PMID- 21865638
TI  - Interaction of oxygen vacancies and lanthanum in Hf-based high-k dielectrics: an
      ab initio investigation.
AB  - The interaction between oxygen vacancies and La atoms in the La doped HfO(2)
      dielectric were studied using first principles total energy calculations. La
      dopants in the vicinity of a neutral oxygen vacancy (V(O)) show lower formation
      energy compared to the La defects far from V(O) centres. La doping in HfO(2)
      leads to the shift of the defect states of oxygen vacancies towards the
      conduction band edge. A statistical average of this shift over several possible
      configurations of La atoms and V(O) shows that the incorporation of La
      effectively passivates the V(O) induced defect states leading to the reduction of
      the gate leakage current and improvement of the device reliability.

PMID- 21865639
TI  - A MUSR study of the magnetoresistive ruthenocuprates RuSr2Nd(1.8
      x)Y0.2Ce(x)Cu2O(10-delta) (x = 0.95 and 0.80).
AB  - Zero field muon spin relaxation (ZF-MUSR) has been used to study the magnetic
      properties of the underdoped giant magnetoresistive ruthenocuprates RuSr(2)Nd(1.8
      x)Y (0.2)Ce(x)Cu(2)O(10-delta) (x = 0.95, 0.80). The magnetoresistance (MR) is
      defined so that MR = ((rho(H)-rho(0))/rho(0)) and the giant magnetoresistive
      ruthenocuprates RuSr(2)Nd(1.8-x)Y(0.2)Ce(x)Cu(2)O(10-delta) exhibit a large
      reduction in electronic resistivity upon application of a magnetic field. The ZF
      MUSR results show a gradual loss of initial asymmetry A(0) at the ruthenium spin
      transition temperature, T(Ru). At the same time the electronic relaxation rate,
      lambda, shows a gradual increase with decreasing temperature below T(Ru). These
      results have been interpreted as evidence for Cu spin cluster formation below
      T(Ru). These magnetically ordered clusters grow as the temperature is decreased
      thus causing the initial asymmetry to decrease slowly. Giant magnetoresistance is
      observed over a wide temperature range in the materials studied and the magnitude
      increases as the temperature is reduced from T(Ru) to 4 K which suggests a
      relation between Cu spin cluster size and |-MR|.

PMID- 21865640
TI  - Phase diagram of CuCrO2 in a magnetic field.
AB  - A simplified model is used to construct the magnetic phase diagram of CuCrO(2) as
      a function of magnetic field and easy-axis anisotropy. Neglecting the weak
      interactions between hexagonal layers, CuCrO(2) is predicted to undergo
      transitions between three different 3-sublattice (SL) phases with increasing
      field: from a chiral, non-collinear phase that exhibits multiferroic behavior, to
      a collinear phase, to a non-chiral, non-collinear phase. The phase diagram also
      contains 1-SL, 4-SL, and 5-SL collinear phases, some of which may be accessible
      in the nonstoichiometric compound CuCrO(2+delta).

PMID- 21865641
TI  - Bond-order correlation and ground-state phase diagram of a one-dimensional V1-V2
      spinless fermion model.
AB  - We establish the ground-state phase diagram of a spinless fermion model with the
      nearest and next-nearest-neighbor repulsions via the density-matrix
      renormalization-group method. The bond-order (BO) correlation function and its
      static structure factor can be employed to accurately determine the BO phase
      boundaries. The first derivative of the charge-density wave (CDW) structure
      factor and the second derivative of the energy are expect to diverge at the 2k(F)
      CDW-BO transition point, which indicates that a second-order transition occurs.
      We determine the metallic-4k(F)-CDW boundary by analyzing the decay behavior of
      the charge correlation function near the transition point.

PMID- 21865642
TI  - A uroguanylin-GUCY2C endocrine axis regulates feeding in mice.
AB  - Intestinal enteroendocrine cells are critical to central regulation of caloric
      consumption, since they activate hypothalamic circuits that decrease appetite and
      thereby restrict meal size by secreting hormones in response to nutrients in the
      gut. Although guanylyl cyclase and downstream cGMP are essential regulators of
      centrally regulated feeding behavior in invertebrates, the role of this
      primordial signaling mechanism in mammalian appetite regulation has eluded
      definition. In intestinal epithelial cells, guanylyl cyclase 2C (GUCY2C) is a
      transmembrane receptor that makes cGMP in response to the paracrine hormones
      guanylin and uroguanylin, which regulate epithelial cell dynamics along the crypt
      villus axis. Here, we show that silencing of GUCY2C in mice disrupts satiation,
      resulting in hyperphagia and subsequent obesity and metabolic syndrome. This
      defined an appetite-regulating uroguanylin-GUCY2C endocrine axis, which we
      confirmed by showing that nutrient intake induces intestinal prouroguanylin
      secretion into the circulation. The prohormone signal is selectively decoded in
      the hypothalamus by proteolytic liberation of uroguanylin, inducing GUCY2C
      signaling and consequent activation of downstream anorexigenic pathways. Thus,
      evolutionary diversification of primitive guanylyl cyclase signaling pathways
      allows GUCY2C to coordinate endocrine regulation of central food acquisition
      pathways with paracrine control of intestinal homeostasis. Moreover, the
      uroguanylin-GUCY2C endocrine axis may provide a therapeutic target to control
      appetite, obesity, and metabolic syndrome.

PMID- 21865643
TI  - Enteric glia are multipotent in culture but primarily form glia in the adult
      rodent gut.
AB  - It is unclear whether neurogenesis occurs in the adult mammalian enteric nervous
      system (ENS). Neural crest-derived cells capable of forming multilineage colonies
      in culture, and neurons and glia upon transplantation into chick embryos, persist
      throughout adult life in the mammalian ENS. In this study we sought to determine
      the physiological function of these cells. We discovered that these cells could
      be identified based on CD49b expression and that they had characteristics of
      enteric glia, including p75, GFAP, S100B, and SOX10 expression. To test whether
      new neurons or glia arise in the adult gut under physiological conditions, we
      marked dividing progenitors with a thymidine analog in rodents under steady-state
      conditions, or during aging, pregnancy, dietary changes, hyperglycemia, or
      exercise. We also tested gut injuries including inflammation, irradiation,
      benzalkonium chloride treatment, partial gut stenosis, and glial ablation. We
      readily observed neurogenesis in a neurogenic region of the central nervous
      system, but not reproducibly in the adult ENS. Lineage tracing of glial cells
      with GFAP-Cre and GFAP-CreERT2 also detected little or no adult ENS neurogenesis.
      Neurogenesis in the adult gut is therefore very limited under the conditions we
      studied. In contrast, ENS gliogenesis was readily observed under steady-state
      conditions and after injury. Adult enteric glia thus have the potential to form
      neurons and glia in culture but are fated to form mainly glia under physiological
      conditions and after the injuries we studied.

PMID- 21865644
TI  - Brain insulin action augments hepatic glycogen synthesis without suppressing
      glucose production or gluconeogenesis in dogs.
AB  - In rodents, acute brain insulin action reduces blood glucose levels by
      suppressing the expression of enzymes in the hepatic gluconeogenic pathway,
      thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether
      a similar mechanism is functional in large animals, including humans, is unknown.
      Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought
      about by infusion of insulin into the head arteries (during a pancreatic clamp to
      maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt,
      altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene
      expression without altering EGP or gluconeogenesis. Rather, brain
      hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output
      (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen
      synthesis. This was associated with decreased levels of glycogen synthase kinase
      3beta (GSK3beta) protein and mRNA and with decreased glycogen synthase
      phosphorylation, changes that were blocked by hypothalamic PI3K inhibition.
      Therefore, we conclude that the canine brain senses physiologic elevations in
      plasma insulin, and that this in turn regulates genetic events in the liver. In
      the context of basal insulin and glucagon levels at the liver, this input
      augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without
      altering EGP.

PMID- 21865645
TI  - A genetically engineered human pancreatic beta cell line exhibiting glucose
      inducible insulin secretion.
AB  - Despite intense efforts over the past 30 years, human pancreatic beta cell lines
      have not been available. Here, we describe a robust technology for producing a
      functional human beta cell line using targeted oncogenesis in human fetal tissue.
      Human fetal pancreatic buds were transduced with a lentiviral vector that
      expressed SV40LT under the control of the insulin promoter. The transduced buds
      were then grafted into SCID mice so that they could develop into mature
      pancreatic tissue. Upon differentiation, the newly formed SV40LT-expressing beta
      cells proliferated and formed insulinomas. The resulting beta cells were then
      transduced with human telomerase reverse transcriptase (hTERT), grafted into
      other SCID mice, and finally expanded in vitro to generate cell lines. One of
      these cell lines, EndoC-betaH1, expressed many beta cell-specific markers without
      any substantial expression of markers of other pancreatic cell types. The cells
      secreted insulin when stimulated by glucose or other insulin secretagogues, and
      cell transplantation reversed chemically induced diabetes in mice. These cells
      represent a unique tool for large-scale drug discovery and provide a preclinical
      model for cell replacement therapy in diabetes. This technology could be
      generalized to generate other human cell lines when the cell type-specific
      promoter is available.

PMID- 21865646
TI  - Foxo1 is required in mouse spermatogonial stem cells for their maintenance and
      the initiation of spermatogenesis.
AB  - Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are
      the foundation for spermatogenesis. Although several factors important for these
      processes have been identified, the fundamental mechanisms regulating SSC self
      renewal and differentiation remain unknown. Here, we investigated a role for the
      Foxo transcription factors in mouse spermatogenesis and found that Foxo1
      specifically marks mouse gonocytes and a subset of spermatogonia with stem cell
      potential. Genetic analyses showed that Foxo1 was required for both SSC
      homeostasis and the initiation of spermatogenesis. Combined deficiency of Foxo1,
      Foxo3, and Foxo4 resulted in a severe impairment of SSC self-renewal and a
      complete block of differentiation, indicating that Foxo3 and Foxo4, although
      dispensable for male fertility, contribute to SSC function. By conditional
      inactivation of 3-phosphoinositide-dependent protein kinase 1 (Pdk1) and
      phosphatase and tensin homolog (Pten) in the male germ line, we found that PI3K
      signaling regulates Foxo1 stability and subcellular localization, revealing that
      the Foxos are pivotal effectors of PI3K-Akt signaling in SSCs. We also identified
      a network of Foxo gene targets--most notably Ret--that rationalized the
      maintenance of SSCs by the Foxos. These studies demonstrate that Foxo1 expression
      in the spermatogenic lineage is intimately associated with the stem cell state
      and revealed what we believe to be novel Foxo-dependent mechanisms underlying SSC
      self-renewal and differentiation, with implications for common diseases,
      including male infertility and testicular cancer, due to abnormalities in SSC
      function.

PMID- 21865648
TI  - Behind an enteric neuron there may lie a glial cell.
AB  - The enteric nervous system (ENS) controls the gastrointestinal system. Enteric
      glia have long been regarded as the essential "glue" of the ENS. Now, however,
      two independent reports in this issue of the JCI provide compelling evidence that
      mouse enteric glia can also be neuronal precursors. These reports show that
      enteric glia give rise to neurons in vitro and that neurogenesis can be
      experimentally induced to occur in vivo in the adult mouse ENS. Unfortunately,
      glia do not constitutively replace neurons, and neurogenesis is not easily
      provoked. Although these new observations make it clear that clinical trials
      using glia to replace enteric neurons are more than premature, they are enticing
      for future research.

PMID- 21865647
TI  - Glial cells in the mouse enteric nervous system can undergo neurogenesis in
      response to injury.
AB  - The enteric nervous system (ENS) in mammals forms from neural crest cells during
      embryogenesis and early postnatal life. Nevertheless, multipotent progenitors of
      the ENS can be identified in the adult intestine using clonal cultures and in
      vivo transplantation assays. The identity of these neurogenic precursors in the
      adult gut and their relationship to the embryonic progenitors of the ENS are
      currently unknown. Using genetic fate mapping, we here demonstrate that mouse
      neural crest cells marked by SRY box-containing gene 10 (Sox10) generate the
      neuronal and glial lineages of enteric ganglia. Most neurons originated from
      progenitors residing in the gut during mid-gestation. Afterward, enteric
      neurogenesis was reduced, and it ceased between 1 and 3 months of postnatal life.
      Sox10-expressing cells present in the myenteric plexus of adult mice expressed
      glial markers, and we found no evidence that these cells participated in
      neurogenesis under steady-state conditions. However, they retained neurogenic
      potential, as they were capable of generating neurons with characteristics of
      enteric neurons in culture. Furthermore, enteric glia gave rise to neurons in
      vivo in response to chemical injury to the enteric ganglia. Our results indicate
      that despite the absence of constitutive neurogenesis in the adult gut, enteric
      glia maintain limited neurogenic potential, which can be activated by tissue
      dissociation or injury.

PMID- 21865649
TI  - Uroguanylin: how the gut got another satiety hormone.
AB  - Prouroguanylin is a gastrointestinal paracrine signal and prohormone that is
      secreted after nutrient ingestion. In this issue of the JCI, Valentino et al.
      show that prouroguanylin is converted to uroguanylin in the CNS, which can
      activate guanylyl cyclase 2C (GUCY2C) receptors in the brain to reduce food
      intake in mice. This 16-amino acid residue peptide is a novel component of the
      gut-brain axis that represents a new and unique opportunity to manipulate gut
      brain signaling for therapeutic intervention in obesity.

PMID- 21865650
TI  - Peripheral glucose homeostasis: does brain insulin matter?
AB  - Much controversy surrounds the relative role of insulin signaling in the brain in
      the control of hepatic glucose metabolism. In this issue of the JCI, Ramnanan and
      colleagues demonstrate that arterial infusion of insulin into the brains of dogs
      reduces net hepatic glucose output without altering endogenous glucose
      production. However, this effect was modest and required both prolonged fasting
      and prolonged exposure of the brain to insulin, raising doubts about the overall
      physiological relevance of insulin action in the brain on hepatic glucose
      metabolism. Given the dominant direct role that insulin plays in inhibiting
      glucose production in the liver, we suggest that the main effect of central
      insulin on hepatic glucose metabolism may be more chronic and assume greater
      significance either when portal insulin is deficient, as occurs during exogenous
      insulin treatment of type 1 diabetes, or when chronic hyperinsulinemia and
      central insulin resistance develops, as occurs in type 2 diabetes.

PMID- 21865651
TI  - Parkin reinvents itself to regulate fatty acid metabolism by tagging CD36.
AB  - Parkinson disease (PD) is a relatively common neurodegenerative disorder
      characterized by the progressive degeneration of dopaminergic neurons in the
      substantia nigra. About 5%-10% of PD cases are inherited. Mutations in the Parkin
      gene, which encodes a protein that can function as an E3 ubiquitin ligase, are a
      common cause of familial PD. Such mutations act in a loss-of-function manner and
      impair the ability of the encoded protein to mediate substrate ubiquitination,
      although the subsequent molecular pathway that precipitates neuronal degeneration
      is poorly defined. In this issue of the JCI, Kim and colleagues describe
      painstaking evidence using a number of dissecting approaches in intact animals
      and cultured cells to functionally link Parkin and the class B scavenger receptor
      CD36, suggesting a novel and complex connection between PD and fatty acid
      metabolism.

PMID- 21865652
TI  - Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human
      cells.
AB  - It has long been hypothesized that abnormalities in lipid biology contribute to
      degenerative brain diseases. Consistent with this, emerging epidemiologic
      evidence links lipid alterations with Parkinson disease (PD), and disruption of
      lipid metabolism has been found to predispose to alpha-synuclein toxicity. We
      therefore investigated whether Parkin, an E3 ubiquitin ligase found to be
      defective in patients with early onset PD, regulates systemic lipid metabolism.
      We perturbed lipid levels by exposing Parkin+/+ and Parkin-/- mice to a high-fat
      and -cholesterol diet (HFD). Parkin-/- mice resisted weight gain,
      steatohepatitis, and insulin resistance. In wild-type mice, the HFD markedly
      increased hepatic Parkin levels in parallel with lipid transport proteins,
      including CD36, Sr-B1, and FABP. These lipid transport proteins were not induced
      in Parkin-/- mice. The role of Parkin in fat uptake was confirmed by increased
      oleate accumulation in hepatocytes overexpressing Parkin and decreased uptake in
      Parkin-/- mouse embryonic fibroblasts and patient cells harboring complex
      heterozygous mutations in the Parkin-encoding gene PARK2. Parkin conferred this
      effect, in part, via ubiquitin-mediated stabilization of the lipid transporter
      CD36. Reconstitution of Parkin restored hepatic fat uptake and CD36 levels in
      Parkin-/- mice, and Parkin augmented fat accumulation during adipocyte
      differentiation. These results demonstrate that Parkin is regulated in a lipid
      dependent manner and modulates systemic fat uptake via ubiquitin ligase-dependent
      effects. Whether this metabolic regulation contributes to premature Parkinsonism
      warrants investigation.

PMID- 21865653
TI  - Finally! A human pancreatic beta cell line.
AB  - For decades, investigators have made numerous attempts to generate human
      pancreatic beta cell lines that could be used to advance beta cell biology,
      facilitate drug discovery, and provide a pathway to beta cell replacement therapy
      for the treatment of diabetes. In this issue of the JCI, Ravassard and colleagues
      report that this has finally been achieved successfully with a multistep process
      that led to the generation of cells, which they termed EndoC-betaH1 cells, that
      secreted insulin in response to glucose challenge.

PMID- 21865655
TI  - Strain-specific differences in perinatal rodent oligodendrocyte lineage
      progression and its correlation with human.
AB  - Progress in the development of rat models of human periventricular white matter
      injury (WMI) has been hampered by uncertainty about the developmental window in
      different rodent strains that coincides with cerebral white matter development in
      human premature infants. To define strain-specific differences in rat cerebral
      white matter maturation, we analyzed oligodendrocyte (OL) lineage maturation
      between postnatal days (P)2 and P14 in three widely studied strains of rat:
      Sprague-Dawley, Long-Evans and Wistar (W). We previously reported that late OL
      progenitors (preOL) are the major vulnerable cell type in human periventricular
      WMI. Strain-specific differences in preOL maturation were found at P2, such that
      the W rat had the highest percentage and density of preOL relative to the other
      strains. Overall, at P2, the state of OL maturation was similar to preterm human
      cerebral white matter. However, by P5, all three strains displayed a similar
      magnitude and extent of OL maturation that persisted with progressive myelination
      between P7 and P14. PreOL were the predominant OL lineage stage present in the
      cerebral cortex through P14, and thus OL lineage maturation occurred latter than
      in white matter. The hippocampus also displayed a later onset of preOL maturation
      in all three strains, such that OL lineage maturation and early myelination was
      not observed to occur until about P14. This timing of preOL maturation in rat
      cortical gray matter coincided with a similar timing in human cerebral cortex,
      where preOL also predominated until at least 8 months after full-term birth.
      These studies support that strain-specific differences in OL lineage immaturity
      were present in the early perinatal period at about P2, and they define a narrow
      window of preterm equivalence with human that diminishes by P5. Later
      developmental onset of preOL maturation in both cerebral cortex and hippocampus
      coincides with an extended window of potential vulnerability of the OL lineage to
      hypoxia-ischemia in these gray matter regions.

PMID- 21865656
TI  - Endoscopic treatment of vesicoureteral reflux using dextranomer/hyaluronic acid
      copolymer in children: results of postoperative follow-up with real-time 3D
      sonography.
AB  - OBJECTIVES: We evaluated whether real-time 3D ultrasound (4D-US) together with
      clinical evaluation is an alternative to voiding cystourethrography (VCUG) after
      endoscopic treatment of vesicoureteral reflux (VUR) in children at postoperative
      follow-up. MATERIAL AND METHODS: We reviewed 178 children who underwent
      endoscopic therapy with dextranomer/hyaluronic acid copolymer in grade II or III
      VUR between 2002 and 2005. 4D-US was performed in all patients 1 day and 3, 9 and
      18 months after endoscopic therapy. Only children with postoperative urinary
      tract infections (UTIs) and/or nonorthotopic position of the bulking agent were
      referred for VCUG. RESULTS: In 93% of the ureteral units, the depot could be
      detected in the orthotopic position after 3, 9 and 18 months. None of these
      children developed UTIs in the postoperative follow-up. Twelve children
      demonstrated a shifting of the depot, indicating a possible therapy failure.
      Eight of these 12 patients (66.7%) presented a positive VCUG, and 50% of them
      sustained UTIs. CONCLUSIONS: 4D-US seems to be a sufficient protocol in the
      follow-up of children after endoscopic treatment of low-grade VUR. VCUG should be
      performed in cases of a shifted position of the depot; invasive investigations
      are unnecessary in asymptomatic children with orthotopic bulk.

PMID- 21865657
TI  - HIV-1 infection suppresses expression of host cell cycle-associated gene PDS5A.
AB  - OBJECTIVE: To unravel the interplay between HIV-1 and its host cell, the effect
      of HIV-1 infection on cellular gene expression was investigated. METHODS: HIV
      1(SF33)-infected and uninfected H9 T cells were screened by differential display
      and RNase protection assay. The finding (PDS5A) was confirmed in HIV-1(Lai)
      infected P4-CCR5 HeLa cells, which were also examined after PDS5A siRNA knockdown
      in regard to HIV-1 replication by quantitative RT-PCR, p24 ELISA and LTR-driven
      beta-galactosidase expression. The PDS5A knockdown effect on cellular gene
      expressions was studied by microarray analysis. PDS5A tissue expression was
      determined by Northern blotting. RESULTS: Regulator of cohesion maintenance,
      homolog A (PDS5A) was found to be down-regulated by HIV-1. When PDS5A was
      suppressed by siRNA, HIV-1 replication was unaffected. PDS5A was found to be
      highly expressed in skeletal muscle tissue, and to lesser degrees in pancreas,
      heart, placenta, lung, kidney, liver and brain. Microarray analysis of PDS5A
      knockdown revealed 91 differential gene products over-representing cell cycle,
      transport and protein stability regulation, including 4 genes (PP2A, RANTES,
      PCAF, TCF7L2) previously reported to interact with HIV-1. CONCLUSION: The data
      show a downregulation of proliferation-associated host gene PDS5A and suggest a
      role of PDS5A in HIV-1-induced cellular pathogenesis but not viral replication.

PMID- 21865658
TI  - Apoptin enhances the oncolytic properties of Newcastle disease virus.
AB  - OBJECTIVE: Naturally occurring strains of Newcastle disease virus (NDV) have
      demonstrated the potential to kill cancer cells in both preclinical and clinical
      studies. Previous studies showed that apoptin, the VP3 protein of chicken
      infectious anemia virus, is a p53-independent, Bcl-2-insensitive apoptotic
      protein with the ability to specifically induce apoptosis in transformed cells.
      In this study, we tested the hypothesis that apoptin enhances NDV-mediated tumor
      cell death. METHODS: Reverse genetics was used to engineer an oncolytic NDV
      strain, FMW, to express apoptin. The antitumor effects of the recombinant virus
      (rFMW/AP) were also evaluated in the tumor cell lines and tumor-bearing mice.
      RESULTS: Compared to the parental strain FMW, rFMW/AP was more potent in killing
      A459 and SMMC7721 tumor cells. Recombinant NDV also exhibited higher efficacy in
      suppressing tumor growth in mice bearing A549-induced tumors. Furthermore,
      rFMW/AP did not display apparent toxic effects in either normal cells or control
      mice. CONCLUSION: Our results suggest that the recombinant NDV expressing apoptin
      is a promising novel antitumor agent.

PMID- 21865659
TI  - Heregulin expression and prognosis in prostate adenocarcinoma.
AB  - BACKGROUND: Heregulins (HRG) are a family of growth factors acting as ligands to
      HER3, HER4 and HER family signalling. HRG has a concentration-dependent
      differential growth effect--low levels mitogenic, high levels inhibitory. HRG
      differentially affects hormone-naive (inhibitory) and castrate-resistant
      (proliferative) prostate adenocarcinoma (CaP) cell lines. We postulate that
      differential HRG expression in CaP will be associated with alteration in tumour
      growth, development and prognosis. PATIENTS AND METHODS: HRG expression was
      assessed in 2 cohorts: cohort 1 of 45 patients with paired hormone-naive and
      castrate-resistant samples, and cohort 2 of 357 hormone-naive samples.
      Correlations between HRG expression and biochemical relapse and survival were
      determined. RESULTS: In cohort 1, hormone-naive samples' high membranous HRG
      expression was associated with increased time to relapse (p = 0.036), time to
      death from relapse (p = 0.002) and overall survival (p = 0.001). Membrane HRG
      fell significantly in post-relapse specimens. In cohort 2, high membranous HRG
      was associated with increased time to relapse (p = 0.004) and overall survival (p
      = 0.044) in patients treated with castration therapy but only with overall
      survival (p = 0.002) in the full cohort. CONCLUSION: High HRG expression is
      associated with improved prognosis in hormone-naive CaP and a fall in expression
      occurs at castration escape indicating a protective role against castrate
      resistance.

PMID- 21865660
TI  - Achievement of sustained viral response after switching treatment from pegylated
      interferon alpha-2b to alpha-2a and ribavirin in patients with recurrence of
      hepatitis C virus genotype 1 infection after liver transplantation: a case
      report.
AB  - We report a case in which sustained viral response was achieved after switching
      treatment from pegylated interferon (PEG-IFN) alpha-2b to alpha-2a and ribavirin
      (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after
      living donor liver transplantation. The patient was a 62-year-old man with liver
      cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa)
      substitutions in the interferon sensitivity-determining region, and had
      substitutions for mutant and wild-type at aa70 and aa91, respectively, in the
      core region. The patient had minor genotype (GG) IL28B single nucleotide
      polymorphisms (rs8099917). He had initially received interferon alpha-2b and RBV
      for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical
      resection of HCC, he subsequently received PEG-IFN alpha-2b and RBV for 1.5
      years, without undetectable viremia during the treatment course. Due to
      recurrence of HCC, the patient received a living donor liver transplantation.
      Later on, hepatitis C relapsed. For the management of relapse, he received
      another course of PEG-IFN alpha-2b and RBV. However, breakthrough viremia
      occurred. PEG-IFN was thus switched from alpha-2b to alpha-2a and RBV for another
      17 months. The patient eventually achieved a sustained viral response.

PMID- 21865661
TI  - Olig2 lineage cells generate GABAergic neurons in the prethalamic nuclei,
      including the zona incerta, ventral lateral geniculate nucleus and reticular
      thalamic nucleus.
AB  - Neuronal differentiation is a crucial event during neural development. Recent
      studies have characterized the development of the diencephalon; however, the
      origins of the primarily GABAergic prethalamic nuclei, including the zona incerta
      (ZI), ventral lateral geniculate nucleus (vLG) and reticular thalamic nucleus
      (RT), remain unclear. Here we characterize Olig2 lineage cells in the developing
      prethalamus using mice in which tamoxifen-induced recombination permanently
      labels Olig2-expressing cells. We show that GABAergic neurons in the prethalamic
      nuclei, including the RT, ZI and vLG, originate from prethalamic Olig2 lineage
      cells. Based on these data and on those derived from short-term lineage-tracing
      data using Olig3-lacZ mice and previous reports, we suggest that vLG cells
      originate from the ventricular zone of the thalamus, zona limitans intrathalamica
      and prethalamus.

PMID- 21865662
TI  - Feasibility of noninvasive near-infrared spectroscopy to diagnose detrusor
      overactivity.
AB  - INTRODUCTION: Near-infrared spectroscopy (NIRS) is an optical technology able to
      detect the hemodynamic changes in biological tissues. Our objective was to
      determine the feasibility of applying NIRS in the noninvasive diagnosis of
      detrusor overactivity (DO). PATIENTS AND METHODS: Comparative analysis was
      performed on 39 involuntary detrusor contractions (IDC) from 23 filling
      cystometries with simultaneous noninvasive NIRS of the bladder in 14 patients
      with DO. Motion artifacts were checked for via surface EMG of the abdominal
      muscles. RESULTS: Thirty-nine IDC were obtained. The median amplitude of rise in
      detrusor pressure at DO was 48 cm H(2)O (range: 5-219). The median filling volume
      at DO was 148 ml (range: 9-531). NIRS curves demonstrated apparently significant
      deviations from baseline in 35 of 39 (90%) DO episodes. All onsets of NIRS
      deviations occurred within the time period of the IDC with a mean delay of 3 s
      (range: 0-9). CONCLUSION: NIRS can be a potential tool for the noninvasive
      diagnosis of DO.

PMID- 21865663
TI  - Comparison of two different suture methods in laparoscopic dismembered
      pyeloplasty.
AB  - OBJECTIVE: Anastomosis of ureteropelvic junction with a laparoscope for the
      treatment of ureteropelvic junction obstruction (UPJO) is a time-consuming and
      technically challenging procedure. We present our experience of laparoscopic
      dismembered pyeloplasty and compare clinical outcomes of two different suture
      techniques. METHODS: From September 2003 to June 2010, 105 laparoscopic
      dismembered pyeloplasties were performed in our department. All procedures were
      done using the retroperitoneal approach. According to the suture methods
      (interrupted or running), the patients were divided into two groups. An
      indwelling stent was placed intraoperatively in an antegrade manner. Data on
      operation time, blood loss and complications were collected. RESULTS: All
      procedures were completed without open conversion. Mean operation time and
      anastomotic time were 96 (55-150) and 36 min (15-70), respectively. A significant
      decrease of operation and anastomosis time was seen when running sutures were
      applied. Mean blood loss was 54 ml (30-100). The total complication rate was
      7.6%. No anastomotic stricture occurred. The average hospitalization stay was 7
      days. During 5-85 months of follow-up, hydronephrosis was alleviated in all
      cases. CONCLUSIONS: Laparoscopic dismembered pyeloplasty for the treatment of
      UPJO can provide satisfactory clinical outcomes. Higher surgical efficiency and
      lower complication rates can be obtained by using the running suture method.

PMID- 21865664
TI  - Mouse models for Down syndrome-associated developmental cognitive disabilities.
AB  - Down syndrome (DS) is mainly caused by the presence of an extra copy of human
      chromosome 21 (Hsa21) and is a leading genetic cause for developmental cognitive
      disabilities in humans. The mouse is a premier model organism for DS because the
      regions on Hsa21 are syntenically conserved with three regions in the mouse
      genome, which are located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. With
      the advance of chromosomal manipulation technologies, new mouse mutants have been
      generated to mimic DS at both the genotypic and phenotypic levels. Further mouse
      based molecular genetic studies in the future may lead to the unraveling of the
      mechanisms underlying DS-associated developmental cognitive disabilities, which
      would lay the groundwork for developing effective treatments for this phenotypic
      manifestation. In this review, we will discuss recent progress and future
      challenges in modeling DS-associated developmental cognitive disability in mice
      with an emphasis on hippocampus-related phenotypes.

PMID- 21865665
TI  - Environmental enrichment rescues postnatal neurogenesis defect in the male and
      female Ts65Dn mouse model of Down syndrome.
AB  - Down syndrome (DS), the most frequent genetic cause of intellectual disability
      and developmental delay, results from impaired neural stem cell proliferation and
      differentiation. Impaired neurogenesis in the neocortex, hippocampus and
      cerebellum is believed to be the underlying cause of learning and behavioral
      deficits in the Ts65Dn mouse model of DS. Aggressive sensorimotor and cognitive
      therapies have shown promise in mitigating the cognitive disabilities in DS but
      these behavioral therapies have not yet been investigated at the cellular level.
      Here, using the Ts65Dn mouse model of DS, we demonstrate that a combination of
      environmental enrichment and physical exercise starting in juvenile mice
      (postnatal day 18) markedly increases cell proliferation, neurogenesis and
      gliogenesis in the hippocampal dentate gyrus (DG) and the forebrain
      subventricular zone (SVZ) of both male and female mice. Enrichment and exercise
      increased the rate of Ts65Dn DG neurogenesis to be comparable to that of the
      nonenriched euploid group, while the effect on SVZ neurogenesis was reduced and
      seen only after prolonged exposure. These results clearly indicate that in a
      comprehensive stimulatory environment, the postnatal DS brain has the intrinsic
      capability of improving neurogenesis and gliogenesis to the levels of normal
      matched controls and that this cellular response underlies the cognitive
      improvement seen following behavioral therapies.

PMID- 21865666
TI  - G-protein-associated signal transduction processes are restored after postweaning
      environmental enrichment in Ts65Dn, a Down syndrome mouse model.
AB  - Individuals with Down syndrome (DS) present cognitive deficits that can be
      improved by early implementation of special care programs. However, they showed
      limited and temporary cognitive effects. We previously demonstrated that
      postnatal environmental enrichment (EE) improved clearly, though temporarily, the
      execution of visuospatial memory tasks in Ts65Dn mice, a DS model bearing a
      partial trisomy of murine chromosome 16; but in contrast to wild-type
      littermates, there was a lack of structural plasticity in pyramidal cell
      structure in the trisomic cerebral cortex. In the present study, we have
      investigated the impact of EE on the function of adenylyl cyclase and
      phospholipase C as a possible mechanism underlying the time-limited improvements
      observed. Basal production of cyclic adenosine monophosphate (cAMP) was not
      affected, but responses to GTPgammaS, isoprenaline, noradrenaline, SKF 38393 and
      forskolin were depressed in the Ts65Dn hippocampus. In EE conditions, cAMP
      accumulation was not significantly modified in control animals with respect to
      nonenriched controls. However, EE had a marked effect in Ts65Dn mice, in which
      cAMP production was significantly increased. Similarly, EE increased
      phospholipase C activity in Ts65Dn mice, in response to carbachol and calcium. We
      conclude that EE restores the G-protein-associated signal transduction systems
      that are altered in Ts65Dn mice.

PMID- 21865667
TI  - Aging in autism spectrum disorders: a mini-review.
AB  - This article addresses an important and barely researched topic: what happens to
      children with autism spectrum disorders when they grow old. We review the small
      published literature on aging in autism. We then consider the relevance of
      research on 'neurotypical' aging in core domains of autistic impairment: social
      cognition, executive function, cognitive style and memory. Research themes from
      the study of normal aging, including cognitive reserve, compensation, quality of
      life, loneliness and physical health are of relevance for future research on
      autism. Studies of aging in autism will be important not only to plan appropriate
      services, but also to shed light on the full developmental trajectory of this
      neurodevelopmental condition, and perhaps provide clues to neuropathology and
      etiology.

PMID- 21865668
TI  - Does automatic transmission improve driving behavior in older drivers?
AB  - BACKGROUND: Most older drivers continue to drive as they age. To maintain safe
      and independent transport, mobility is important for all individuals, but
      especially for older drivers. OBJECTIVE: The objective of this study was to
      investigate whether automatic transmission, compared with manual transmission,
      may improve the driving behavior of older drivers. METHOD: In total, 31 older
      drivers (mean age 75.2 years) and 32 younger drivers - used as a control group
      (mean age 39.2 years) - were assessed twice on the same fixed route; once in a
      car with manual transmission and once in a car with automatic transmission. The
      cars were otherwise identical. The driving behavior was assessed with the Ryd On
      Road Assessment driving protocol. Time to completion of left turns (right-hand
      side driving) and the impact of a distraction task were measured. RESULTS: The
      older group had more driving errors than the younger group, in both the manual
      and the automatic transmission car. However, and contrary to the younger drivers,
      automatic transmission improved the older participants' driving behavior as
      demonstrated by safer speed adjustment in urban areas, greater maneuvering
      skills, safer lane position and driving in accordance with the speed regulations.
      CONCLUSION: Switching to automatic transmission may be recommended for older
      drivers as a means to maintain safe driving and thereby the quality of their
      transport mobility.

PMID- 21865669
TI  - Combination of preS deletions and A1762T/G1764A mutations in HBV subgenotype C2
      increases the risk of developing HCC.
AB  - BACKGROUND: The interactions among hepatitis B virus (HBV) mutations in
      developing hepatocellular carcinoma (HCC) remain unclear and thus we investigated
      the risk of HCC related with single or multiple HBV mutations in Korean patients
      infected with HBV subgenotype C2. METHODS: From January 2003 to December 2008,
      HBV isolates from 135 patients with HCC were compared with those from 135
      patients without HCC, matching for age, gender, and HBeAg status. The prevalence
      of preS deletions and G1896A and A1762T/G1764A mutations was evaluated. RESULTS:
      The frequency of preS deletions significantly differed between the non-HCC and
      HCC groups, with 6 (4.4%) versus 25 (18.5%) patients, respectively (p < 0.001).
      Additionally, the frequency of A1762T/G1764A mutations was higher in the HCC than
      the non-HCC group [82 (60.7%) versus 30 (22.2%), p < 0.001]. For combined
      mutations, the odds ratio (OR) was highest in patients with both preS deletions
      and the A1762T/G1764A mutation, with 1 (0.7%) versus 11 (8.1%) patients (p =
      0.005; OR 11.887). CONCLUSIONS: HCC was associated with preS deletions and
      A1762T/G1764A mutations, and the combination of both mutations had a stronger
      association with HCC in Korean patients infected with HBV subgenotype C2.

PMID- 21865670
TI  - Diagnostic value of the nuclear matrix protein 22 test and urine cytology in
      upper tract urothelial tumors.
AB  - OBJECTIVE: To investigate the diagnostic value of the nuclear matrix protein 22
      (NMP22) test in comparison to urine cytology for the detection of upper tract
      urothelial carcinoma. PATIENTS AND METHODS: Patients with transitional cell
      carcinoma of the upper urinary tract (n = 34) and patients with renal calculosis
      (n = 25) were included in this study. Voided urine samples and separated catheter
      urine specimens were assayed for NMP22 and cytological examination. RESULTS: The
      sensitivity of the NMP22 test in separated and voided urine was 73.2 and 70.5%,
      respectively, compared to 64.7 and 58.8% of urine cytology. The specificity of
      the NMP22 test in separated and voided urine was 88 and 92%, respectively,
      compared to 96 and 96% of urine cytology. The combination of separated and voided
      urine is the best method because the sensitivity is 79.41% and specificity 88%.
      There is a high agreement of the NMP22 test in voided and separated urine (kappa
      = 0.795, p < 0.01), indicating that the voided urine is adequate for diagnosis.
      CONCLUSIONS: The NMP22 test has higher sensitivity but lower specificity than
      cytology. The combination of these two tests could be a very useful diagnostic
      method for detection of upper urothelial tumors.

PMID- 21865671
TI  - Improved automated screening of diabetic retinopathy.
AB  - AIM: To assess a two-step automated system (RetmarkerSR) that analyzes retinal
      photographs to detect diabetic retinopathy for the purpose of reducing the burden
      of manual grading. METHODS: Anonymous images from 5,386 patients screened in 2007
      were obtained from a nonmydriatic diabetic retinopathy screening program in
      Portugal and graded by an experienced ophthalmologist. RetmarkerSR earmarked
      microaneurysms, generating two outputs: 'disease' or 'no disease'. A second-step
      analysis, based on coregistration, combining two visits, was subsequently
      performed in 289 patients who underwent repeated examinations in 2008. The study
      was extended by analyzing all referrals considered urgent by the ophthalmologist
      from 2001 to 2007. Results were compared with those obtained by manual grading.
      RESULTS: The RetmarkerSR classified in a first-step analysis 2,560 patients
      (47.5%) as having 'no disease' and 2,826 patients (52.5%) as having 'disease',
      thus requiring manual grading. RetmarkerSR detected all eyes considered urgent
      referrals. The two-step analysis further reduced the number of false-positive
      results by 26.3%, indicating an overall sensitivity of 95.8% and a specificity of
      63.2%. CONCLUSION: Automated grading of diabetic retinopathy may safely reduce
      the burden of grading patients in diabetic retinopathy screening programs. The
      novel two-step automated analysis system offers improved sensitivity and
      specificity over published automated analysis systems.

PMID- 21865672
TI  - Irradiation-induced morphea: x-rays as triggers of autoimmunity.
AB  - We report on 3 females with breast cancer who developed morphea at the site of
      post-surgery radiotherapy. One was suffering from other autoimmune skin diseases
      before the diagnosis and treatment of breast cancer. Postirradiation morphea is a
      potential complication after radiotherapy, particularly radiotherapy for cancer.
      This troublesome skin disease can occur months to years after treatment, and is
      associated with remarkable morbidity and pain, and also cosmetic aspects.
      Therefore, it is crucial to be aware of this condition, and to try to identify
      patients who might be at an increased risk of developing morphea.

PMID- 21865673
TI  - Isotretinoin and the risk of cardiovascular, cerebrovascular and thromboembolic
      disorders.
AB  - BACKGROUND: Case reports suggest that isotretinoin use is associated with an
      increased risk of cardiovascular disorders; however, the clinical significance
      has not been determined. OBJECTIVE: To determine whether isotretinoin increases
      the risk of cardiovascular outcomes. METHODS: A case crossover study was
      performed among subjects who filled >=1 isotretinoin prescription during 1984
      2003. Cases were defined as those with a first-ever diagnosis or hospitalization
      for acute myocardial infarction (MI), stroke, phlebitis/thrombophlebitis,
      pulmonary embolism (PE) or thrombosis. Exposure to isotretinoin in a 5-month
      hazard period immediately prior to the index date (calendar date of the diagnosis
      or hospitalization for the study outcomes) was compared to a 5-month control
      period. Odds ratios (ORs) along with 95% confidence intervals (CIs) were
      estimated using conditional logistic regression. RESULTS: Of 30,496 isotretinoin
      users identified, 872 (3%) cases met the inclusion criteria; 381 (43.7%) had a
      stroke, 268 (30.7%) phlebitis/thrombophlebitis, 133 (15.3%) MI, 61 (7.0%) PE and
      29 (3.3%) thrombosis. When stratified according to type of outcome, ORs were 0.75
      (95% CI: 0.38-1.47), 1.31 (95% CI: 0.64-2.69) and 2.00 (95% CI: 0.50-8.00) for
      stroke, phlebitis/thrombophlebitis and MI, respectively. CONCLUSION: No
      statistically significant association was found between isotretinoin and
      cardiovascular, cerebrovascular and thromboembolic outcomes.

PMID- 21865674
TI  - Th1, Th2, Th17 and regulatory T cell pattern in psoriatic patients: modulation of
      cytokines and gene targets induced by etanercept treatment and correlation with
      clinical response.
AB  - BACKGROUND: Psoriasis is sustained by pro-inflammatory CD4+ T helper cells mainly
      belonging to the Th1, Th17 and Th22 lineage. OBJECTIVE: To identify whether
      treatment with the anti-tumour-necrosis-factor antagonist etanercept is able to
      induce significant modulations in transcription factor and cytokine mRNA gene
      expressions related to the different T cell immune response polarization (Th1,
      Th2, Th17 and regulatory T cells, Treg and to correlate them with clinical
      response. METHODS: The study population included 19 psoriasis patients treated
      with etanercept and 19 healthy subjects. Blood samples were collected at baseline
      and every 4 weeks during treatment. Taqman quantitative real-time polymerase
      chain reaction was applied to analyse the expression of: Stat-4, T-bet, IL-12p35
      and IFN-gamma (Th1-related); GATA-3, IL-4 (Th2-related); Stat-3, RORgammat, IL
      23p19 (Th17-related); Foxp3, IL-2 (Treg-related). Flow cytometry was applied to
      analyse CD4+CD25+(bright)Foxp3+ cells in peripheral blood. RESULTS: Upregulation
      of Th1 and Th17 and downregulation of Treg subsets was found at baseline. The
      response to etanercept could be associated with a significant reversal of the
      Th1/Th17 activation, and a concomitant upregulation of Th2 and Treg subsets.
      CONCLUSION: Our data may contribute to a better understanding of the mechanisms
      underlying the achievement of clinical response in psoriasis and could be helpful
      for the identification of early predictive markers of response.

PMID- 21865675
TI  - 'EASIdig'--a digital tool to document disease activity in atopic dermatitis.
AB  - BACKGROUND: Different scoring systems have been developed to determine the
      severity of atopic dermatitis (AD); the SCORAD (Scoring Atopic Dermatitis) and
      EASI (Eczema Area and Severity Index) are among the best-validated scoring
      systems. OBJECTIVE: The aim of this study was to produce a rational quality
      control for routine clinical use by using the modern facilities of digital
      imaging. METHODS: 63 AD patients were scored by a single person at each visit
      using the SCORAD and EASI scoring methods. Images were taken and rated by two non
      dermatology physicians trained in the scoring system. In addition, blood samples
      were taken for the determination of total IgE, eosinophils and eosinophilic
      cationic protein. RESULTS: The EASI score established from the digital images,
      hereby named 'EASIdig', correlated at all visits with the results of the SCORAD
      and EASI. Together with immunological parameters, they also reflected changes of
      disease severity during the 3 time points. CONCLUSION: The digital evaluation of
      the EASI is a reliable tool for the digital assessment of severity and extent of
      AD.

PMID- 21865676
TI  - Molecular karyotyping: from microscope to SNP arrays.
AB  - Chromosomal rearrangements are an important cause of distinctive and recognizable
      clinical phenotypes. For many years conventional karyotyping has been a
      successful tool to detect such chromosomal rearrangements. However, this
      technique has a limited resolution of 5-10 Mb. In the past decades, the
      development of new high-resolution techniques has led to the field of molecular
      cytogenetics. One of the most significant changes has been the use of molecular
      karyotyping by high-resolution whole-genome array techniques in the diagnostic
      setting. This technology is able to detect chromosomal aberrations at a
      resolution beyond the detection level of conventional karyotyping. Many new
      microdeletion and microduplication syndromes have been identified by this new
      method. In this review, we will focus on the most commonly used (molecular)
      cytogenetic techniques.

PMID- 21865677
TI  - Imaging geographic atrophy in age-related macular degeneration.
AB  - Advances in retinal imaging technology have largely contributed to the
      understanding of the natural history, prognostic markers and disease mechanisms
      of geographic atrophy (GA) due to age-related macular degeneration. There is
      still no therapy available to halt or slow the disease process. In order to
      evaluate potential therapeutic effects in interventional trials, there is a need
      for precise quantification of the GA progression rate. Fundus autofluorescence
      imaging allows for accurate identification and segmentation of atrophic areas and
      currently represents the gold standard for evaluating progressive GA enlargement.
      By means of high-resolution spectral-domain optical coherence tomography,
      distinct microstructural alterations related to GA can be visualized.

PMID- 21865678
TI  - Prevention of neural-tube defects with periconceptional folic acid, methylfolate,
      or multivitamins?
AB  - BACKGROUND/AIMS: To review the main results of intervention trials which showed
      the efficacy of periconceptional folic acid-containing multivitamin and folic
      acid supplementation in the prevention of neural-tube defects (NTD). METHODS AND
      RESULTS: The main findings of 5 intervention trials are known: (i) the efficacy
      of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled
      trial resulted in an 83-91% reduction in NTD recurrence, while the results of the
      Hungarian (ii) randomized controlled trial and (iii) cohort-controlled trial
      using a multivitamin containing 0.8 mg folic acid showed 93 and 89% reductions in
      the first occurrence of NTD, respectively. On the other hand, (iv) another
      multicenter randomized controlled trial proved a 71% efficacy of 4 mg folic acid
      in the reduction of recurrent NTD, while (v) a public health-oriented Chinese-US
      trial showed a 41-79% reduction in the first occurrence of NTD depending on the
      incidence of NTD. CONCLUSIONS: Translational application of these findings could
      result in a breakthrough in the primary prevention of NTD, but so far this is not
      widely applied in practice. The benefits and drawbacks of 4 main possible uses of
      periconceptional folic acid/multivitamin supplementation, i.e. (i) dietary
      intake, (ii) periconceptional supplementation, (iii) flour fortification, and
      (iv) the recent attempt for the use of combination of oral contraceptives with 6S
      5-methytetrahydrofolate (methylfolate), are discussed. Obviously, prevention of
      NTD is much better than the frequent elective termination of pregnancies after
      prenatal diagnosis of NTD fetuses.

PMID- 21865679
TI  - Clinical manifestations and pathogenesis of tonsillar focal diseases: IgA
      nephropathy and palmoplantar pustulosis.
AB  - Tonsillar focal disease is defined as clinical disorders in the distant organ
      from the tonsil that are caused by the tonsils without any symptoms of the tonsil
      itself. Palmoplantar pustulosis and IgA nephropathy are known typical tonsillar
      focal diseases. In this paper, the clinical outcome of tonsillectomy and the
      etiological evidence of related diseases are reviewed.

PMID- 21865680
TI  - Moving towards a new era in the research of tonsils and mucosal barriers.
AB  - The palatine and nasopharyngeal tonsils (adenoids) are lymphoepithelial tissues
      located in strategic anatomical areas of the oral pharynx and nasopharynx. These
      immunocompetent tissues represent the first line of defense against ingested or
      inhaled foreign proteins such as bacteria, viruses, or food antigens.
      Accompanying the advances being made in the field of medicine today, the role of
      the tonsils in immunocompetence is becoming extremely important. Upper
      respiratory tract infections such as acute otitis media, acute rhinosinusitis and
      acute pharyngo-tonsillitis are diseases that occur with extremely high frequency,
      and the antimicrobial agents used to treat these diseases account for a large
      proportion of health care costs. The increasingly refractory nature of upper
      respiratory tract infections caused by drug-resistant bacteria has become a major
      worldwide concern. The elucidation of the immune functions of the tonsils and
      mucosal membranes of the upper respiratory tract is considered to have important
      significance. The tonsils are also considered to play an important role as one of
      the causes of sleep apnea syndrome, and have been reported to be intimately
      involved in the manifestation of IgA nephropathy and palmoplantar pustulosis, a
      kind of skin disorder. Interest has continued to grow in this symposium with each
      session ever since it was first held in Kyoto, Japan in 1987. Since then, the
      symposium has been held every 3-4 years; in Pavia in 1991, in Sapporo in 1995, in
      Ghent in 1999, in Wakayama in 2003, and in Siena in 2006. Since the 5th symposium
      in Wakayama, the topics were extended to mucosal barriers of upper airways
      including the mucosal immune system, innate immunity, and mucosal vaccine. Recent
      fine technologies and information on molecular biological approaches for upper
      airways will continue to advance our understanding of epidemiology, etiology,
      pathogenesis, diagnosis and management of tonsil-related disorders and various
      upper respiratory tract infections such as otitis media and rhinosinusitis.
      Moreover, in the era of drug-resistant microbes, we should exert more effort to
      develop powerful and effective mucosal vaccines against pathogens in upper
      airways.

PMID- 21865681
TI  - Immune functions of nasopharyngeal lymphoid tissue.
AB  - This brief review will focus on nasopharynx-associated lymphoid tissue as a
      unique inductive immune site for B cell responses and plasma cell generation. The
      anatomical and immunological characteristics of Waldeyer's lymphoid ring should
      make the nasal route for vaccine administration highly relevant in future
      clinical trials to stimulate both mucosal and systemic immunity. In this context,
      the potential immunological consequences of removing both the tonsils and the
      adenoids have to be considered.

PMID- 21865682
TI  - Elicitation of mucosal immunity by proteins of Streptococcus pneumoniae.
AB  - Pneumococcal diseases such as otitis media, pneumonia, and meningitis are
      invariably preceded by nasopharyngeal colonization, and herd immunity against
      pneumococcal disease requires protection against colonization. An early study in
      mice demonstrated that mucosal immunization with cholera toxin B subunit as
      adjuvant could elicit solid mucosal immunity. Recent data from several
      laboratories provides support for three different mechanisms by which adaptive
      immunity can provide protection against colonization. (1) IL-17-dependent T cell
      immunity can recruit PMN to sites of colonization. This IL-17-dependent immunity
      can be elicited by immunization with antigen plus a mucosal adjuvant, or can be
      elicited by colonization itself. (2) Immunity against colonization can be
      mediated by mucosal IgA and at the mucosal surface passive mucosal IgA antibody
      provides much better protection against carriage than passive IgG antibody. (3)
      Complement-fixing IgG antibody can protect against colonization and may act by
      protecting against colonization of bacteria.

PMID- 21865683
TI  - Mucosal immune barrier and antigen-presenting system in human nasal epithelial
      cells.
AB  - The upper respiratory tract including the nasal cavity, which is the first site
      of invading antigen exposure, plays a crucial role in host defense via the
      mucosal immune response. The epithelium of nasal mucosa forms a continuous
      barrier against a wide variety of exogenous antigens. The epithelial barrier
      function is regulated in large part by the apical-most intercellular junction,
      referred to as the tight junction. Antigen-presenting cells, particularly
      dendritic cells (DCs), are known to play an important role in human nasal mucosa.
      Recently, the author and colleagues discovered a new mechanism for pathogen
      uptake in the nasal mucosa, by which DCs open the tight junctions between
      epithelial cells and send dendrites outside the epithelium to directly sample the
      pathogen. In order to preserve the integrity of the epithelial barrier and
      penetrate beyond well-developed epithelial tight junctions, DCs express tight
      junction proteins. We also found that these DCs are activated by nasal epithelial
      derived TSLP induced by stimuli such as cytokines and Toll-like receptor ligands.
      In this lecture, I will talk about the novel mechanisms in host defense in terms
      of innate immunity of the nasal mucosa from the point of view of the mucosal
      barrier function.

PMID- 21865684
TI  - Craniofacial mucosal immune system: importance of its unique organogenesis and
      function in the development of a mucosal vaccine.
AB  - Mucosa-associated lymphoid tissues (MALT) play a critical role as inductive sites
      for the initiation of antigen-specific protective immunity against pathogens
      penetrating the mucus membranes. Nasopharynx-associated lymphoid tissue (NALT),
      situated at the bottom of the rodent nasal cavity, is thought to be an important
      site for the induction of antigen-specific immune response to inhaled antigens.
      In addition, we have recently shown that tear duct-associated lymphoid tissue
      (TALT), present in the murine tear duct bridging the ocular and nasal cavities,
      is involved in the induction and regulation of both nasal and ocular immunity.
      Interestingly, cellular requirements for the organogenesis of NALT and TALT are
      quite different from those of other MALT (e.g. Peyer's patches; PPs) and
      peripheral lymphoid tissues. Moreover, mucosal imprinting molecules of NALT and
      TALT inducer cells are totally independent of currently known chemokines and
      adhesion molecules in PPs and lymph nodes, such as the CXCR5-CXCL13, alpha4beta1
      integrin-vascular cell adhesion molecule-1 (VCAM1), and CCR9-CCL25 axes. NALT and
      TALT lymphocytes are also independent of these tissue-specific migration
      molecules. Together with already-characterized conjunctiva-associated lymphoid
      tissue (CALT ), which has been demonstrated to play a critical role in ocular
      defense, the MALT associated with the head region seems to be coordinately
      organizing the unique craniofacial mucosal immune system of the ocular, nasal,
      oral-pharynx mucus membranes. Clarification of the immunological network of this
      unique craniofacial immune system will facilitate the development of a safe and
      effective mucosal vaccine against respiratory and ocular infections.

PMID- 21865685
TI  - Tonsillectomy with steroid pulse: a curative therapy for IgA nephropathy.
AB  - IgA nephropathy (IgAN), the most common form of primary glomerulonephritis
      progressing to end-stage renal disease (ESRD), has been regarded as an incurable
      disease. However, in recent years, it has been demonstrated that combined
      tonsillectomy with steroid pulse (TS) therapy, if administrated in the relatively
      early stage of the disease, can yield clinical remission in patients with IgAN.
      However, clinical remission is no longer obtained when the same treatment is
      administrated in cases with more advanced disease and/or a longer duration of
      nephropathy. Thus, the paradigm of managing IgAN patients is shifting in Japan
      from 'slowing the progression and the delaying the onset of ESRD' (by
      conventional therapy using a RAS inhibitor and/or corticosteroids at low doses in
      selected patients with advanced IgAN) to 'achieving remission' by the TS therapy
      in patients with early disease. In the new paradigm aimed at clinical remission,
      the principle for initiation of TS therapy should be 'the earlier, the better'.

PMID- 21865686
TI  - Recent advances in IgA nephropathy--the glomerulopodocytic-tubular communication.
AB  - IgA nephropathy (IgAN) is characterized by mesangial deposition of pathogenic
      polymeric IgA1 with rare deposits in the tubular epithelial cells (TEC).
      Recently, a novel mechanism involving a glomerulopodocytictubular cross-talk in
      the development of tubulointerstitial damage in IgAN has been revealed. Podocytes
      are positioned strategically along the glomerulotubular axis and plays an
      important role in mediating the glomerulotubular cross-talk. In IgAN, podocyte
      markers are reduced in the glomeruli. In vitro study implicates humoral factors
      (predominantly tumor necrosis factor-alpha and transforming growth factor-beta)
      released from mesangial cells alter the glomerular permeability in the event of
      proteinuria and tubulointerstitial injury in IgAN. These mediators released from
      mesangial cells after IgA deposition further activate TEC leading to subsequent
      inflammatory changes in the renal tubulointerstitium.

PMID- 21865687
TI  - Immunomodulatory agents against IgA nephropathy.
AB  - Synthesis of aberrant IgA molecules as the key pathogenetic mechanism of
      immunoglobulin A nephropathy (IgAN) apparently forms a potential scientific
      rationale for applying immunomodulatory agents in the treatment of IgAN. There is
      evidence that corticosteroids can steadily reduce proteinuria and slow down renal
      progression. Evidence that pulse steroid plus intravenous or oral
      cyclophosphamide can retard the rate of progression of advanced IgAN was provided
      by several groups worldwide. Cyclosporin is generally not used to treat IgAN. The
      efficacy of azathioprine is equivocal. Mycophenolate mofetil reduces proteinuria
      by up to 30% and favorably impacts renal survival in Chinese patients with mild
      histologic lesions, but these results were not achieved in Caucasians with more
      advanced disease. In conclusion, the choice of immunomodulatory therapy remains
      controversial. We advocate the use of immunomodulatory agents as an adjunctive
      therapy in patients with proteinuria>1 g/day despite achieving target blood
      pressure with full renin-angiotensin blockade. More aggressive therapy should be
      reserved for patients with nephrotic-range proteinuria, crescentic lesions and/or
      rapidly progressive renal failure.

PMID- 21865688
TI  - Indication criteria for tonsillectomy in IgA nephropathy patients.
AB  - We proposed the following indication criteria for tonsillectomy in patients with
      IgA nephropathy. (1) IgA nephropathy has been definitively diagnosed by an
      evaluation of the renal glomeruli during renal biopsy. (2) Tonsillectomy is
      indicated for patients who demonstrate grade I-III renal pathology and a serum
      creatinine level of 2.0 mg/dl or less during renal biopsy. However, even among
      patients who demonstrate grade IV disease or a serum creatinine level higher than
      2.0 mg/dl during renal biopsy, surgery should be considered in the absence of
      contraindications for tonsillectomy, such as renal hypofunction, providing the
      patient wants to undergo surgery and informed consent is obtained. (3) The
      patient's medical history includes deterioration of urine findings during
      tonsillitis or acute upper respiratory inflammation.(4) Buried tonsils and the
      attachment of pus plugs to the tonsillar crypt are observed as local findings of
      the palatine tonsil. (5) Positive findings, especially positive urine findings
      (hematuria), are detected on the tonsillar provocation test. Items (1) and (2)
      are essential. Items (3) to (5) are indicative, as their inclusion has not been
      supported by previous studies.

PMID- 21865689
TI  - Periodontal and ENT therapy in the treatment of pediatric Henoch-Schonlein
      purpura and IgA nephropathy.
AB  - Henoch-Schonlein purpura (HSP) and IgA nephropathy (IgAN) are both IgA1-related
      vasculitis caused by vascular deposition of IgA1-containing immune complexes. A
      pathological role of the tonsils in the development of HSP and IgAN has been
      suggested. Tonsils are a mucosaassociated lymphoid organ. Since oral and
      sinonasal cavities are anatomically directly connected to the tonsils, delivering
      exogenous antigens into the tonsils to induce local and systemic antibody
      responses, we examined the infectious status of these cavities when we treated
      HSP and IgAN. In 40 HSP children (6.7+/-2.5 years), apical periodontitis,
      rhinosinusitis, and otitis media were identified in 21 (53%, 4.9+/-2.8 affected
      teeth), 19 (48%), and 4 (10%) of them, whereas in 11 IgAN children (10.4+/-2.5
      years), these diseases were observed in 6 (55%, 5.8+/-4.6 affected teeth), 2
      (18%), and 0 (0%) of them, respectively. We first treated the patients with
      extensive eradiation of infectious foci, including antimicrobial treatment and
      root canal therapy. In 31 HSP patients, such dental and/or ENT therapy resulted
      in a complete cure without development of nephritis or recurrent attacks. For the
      remaining 9 HSP and 11 IgAN patients, we further performed tonsillectomy plus
      methylprednisolone (MP) pulse therapy to control their intractable symptoms,
      including aggravated purpura, recurrent HSP attacks or nephritis. Using this
      therapeutic strategy, all of the HSP patients attained clinical remission. All of
      the IgAN patients with various histological grades also achieved normalization of
      urinalysis by 7.2+/-5.7 months after the start of steroid therapy. No relapses
      were observed in both diseases during followup for 2-10 years. In pediatric HSP
      and IgAN, apical periodontitis and rhinosinusitis may be involved in abnormal
      immune responses in both the tonsils and whole body. We conclude that extensive
      elimination of these infectious foci is beneficial to optimize the effect of
      tonsillectomy plus MP pulse therapy.

PMID- 21865690
TI  - Tonsillectomy combined with steroid pulse therapy induces clinical remission of
      IgA nephropathy.
AB  - Tonsillectomy combined with steroid pulse therapy has been a popular approach to
      treating IgA nephropathy (IgAN) in Japan for several years. However, little is
      understood about how such combined therapy affects the clinical course of IgAN.
      We therefore compared the effects of the combined therapy with those of steroid
      pulsing alone in a controlled study of patients with IgAN. The achievement ratio
      of clinical remission (CR), defined as the disappearance of urinary protein (UP)
      and occult blood (UOB), were compared between tonsillectomy combined with steroid
      pulse therapy (n=35) and steroid pulse monotherapy (n=20). The CR rate was higher
      in the group given combined therapy than that given monotherapy at the final
      observation 54.0+/-21.2 months after the initial treatment (54.3 vs. 25.0%,
      p=0.033). The Cox regression model showed that the combined therapy caused UP to
      disappear 6-fold more effectively than monotherapy. These findings suggest that
      tonsillectomy combined with steroid pulse therapy induces CR in patients with
      IgAN. Meanwhile, the indications for this therapy and verification of its
      positive longterm prognosis require urgent validation.

PMID- 21865691
TI  - Aberrant glycosylation of IgA1 and anti-glycan antibodies in IgA nephropathy:
      role of mucosal immune system.
AB  - IgA nephropathy (IgAN), the most common glomerulonephritis, is characterized by
      mesangial IgA1-containing immunodeposits, proliferation of mesangial cells, and
      matrix expansion. Clinical onset is frequently heralded by synpharyngitic
      hematuria, macroscopic hematuria during an upper-respiratory tract infection.
      Clinical and laboratory data support a postulated extrarenal origin of the
      glomerular IgA1, likely derived from circulating immune complexes containing
      polymeric IgA1, deficient in galactose in the hinge-region O-glycans, bound by
      antiglycan antibodies. This aberrant IgA1 is produced by IgA1-secreting cells
      with abnormal activities of specific glycosyltransferases. The galactose
      deficiency affects IgA1 induced by mucosal antigens and elevated circulating
      levels of this abnormal IgA1 are hereditable, suggesting interactions of genetic
      and environmental factors. An abnormal mucosal immune response resulting in
      production of galactose-deficient IgA1 in IgAN patients is supported by several
      observations: the aberrant glycosylation affects mostly polymeric IgA1 produced
      by mucosal-associated IgA1-secreting cells (including those from tonsils), the
      synpharyngitic nature of the macroscopic hematuria, and the association of
      disease severity with polymorphisms of a pattern-recognition receptor, TLR9.
      Thus, IgAN is an auto-immune disease, induced by mesangial deposition of
      circulating complexes containing galactose-deficient IgA1. The aberrant
      glycosylation of IgA1 may reflect abnormal mucosal immune responses to infections
      of the upper respiratory tract in genetically predisposed individuals.

PMID- 21865692
TI  - Reevaluation of the mucosa-bone marrow axis in IgA nephropathy with animal
      models.
AB  - Impaired immune regulation along the 'mucosa-bone marrow axis' has been
      postulated to play an important role in the pathogenesis of IgA nephropathy
      (IgAN). Animal models have allowed us to study such changes in detail. Recently,
      we established several useful animal models, including IgAN-prone mice. Using
      these animal models, our group is approaching the underlying mechanisms by which
      bone marrow and mucosal cell interrelate and finally induce this disease.
      Accumulating evidence from these approaches suggests that there is dysregulation
      of innate and cellular immunity in IgAN resulting in changes in the mucosal
      immune system. These changes appear to be closely linked to disruption of mucosal
      tolerance, resulting in abnormal priming and dissemination of cells to sites such
      as the bone marrow where they are responsible for synthesis of nephritogenic IgA.
      Our clinical studies further support these ideas and indicate that the tonsils
      may be a major mucosal priming site in human IgAN. In addition, our findings also
      suggest clinical application of nephritogenic IgA (IgA1) as a biological marker
      and possible future treatment strategies that focus on manipulating the priming
      and dissemination of these memory cells in order to prevent the appearance of
      nephritogenic IgA (IgA1) in the systemic compartment.

PMID- 21865693
TI  - IgA nephropathy and aberrant glycosylation of tonsillar, serum and glomerular
      IgA1.
AB  - Human IgA1, which is the predominant subtype deposited in the glomeruli in IgA
      nephropathy (IgAN), has a unique mucin-like structure in its hinge region.
      Several studies suggested that the IgA1 molecules in IgAN patients had an
      aberrant structure of O-glycans. The paper summarizes the analyses of O-glycan
      structure in the IgA1 molecules taken from tonsils, sera and glomeruli of
      patients with IgAN. Hypoglycosylation, especially hypogalactosylation of O
      glycans has been observed not only in serum and glomerular IgA1 but also in
      tonsillar IgA1.

PMID- 21865694
TI  - Abnormalities of glycogenes in tonsillar lymphocytes in IgA nephropathy.
AB  - Glycosylation, which represents the most complex post-translational modification,
      plays a pivotal role during protein maturation, and is orchestrated by numerous
      glycosyltransferases. Aberrant O-glycosylation of serum and tonsillar IgA1 is
      presumed to be one of the pathogeneses of IgA nephropathy (IgAN). However, the
      synthesis of underglycosylated IgA1 in tonsils has not yet been characterized.
      This study investigated tonsillar B lymphocytes of IgAN using tonsils from
      patients with chronic tonsillitis and sleep apnea syndrome. Gene expression of
      beta1,3-galactosyltransferase (beta3GalT), Cosmc, UDP-N-acetyl-alpha-D
      galactosamine: polypeptide N-acetylgalactosaminyl-transferase 2, were
      significantly down regulated in tonsillar CD19-positive B lymphocytes from IgAN
      patients compared to control as determined by real-time RT-PCR. In contrast, the
      level of sialyltransferase was not significantly different among the three
      groups. Tonsillar B cell beta3GalT gene expression significantly correlated with
      estimated GFR and negatively correlated with proteinuria and glomerular or
      interstitial injury score. Double immunofluorescent staining showed that some IgA
      positive cells in the intrafollicular area were also positive for beta3GalT
      staining. Western blotting showed the protein expression of beta3GalT in the
      tonsils to significantly decrease in IgAN in comparison to the controls. These
      data suggest the downregulation of beta3GalT in tonsillar B lymphocytes to be
      closely associated with the clinical characteristics of IgAN.

PMID- 21865695
TI  - Microarray analysis of tonsils of IgA nephropathy patients.
AB  - IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Its close
      relation with the tonsils is well known because tonsillitis sometimes causes
      aggravation of urinary findings or macrohematuria. However, the genes specific to
      the tonsils of IgAN patients are not clarified. To clarify the specific gene
      expression in the tonsils of IgAN patients, we performed tonsillectomy and
      corticosteroid IV therapy as a treatment of IgAN, analyzed the gene expression in
      the tonsils by microarray and compared it with that in tonsils from chronic
      tonsillitis patients. The upregulated genes seem to be categorized into two
      groups: muscle-related genes and immunerelated genes. The downregulated genes
      include the polymeric Ig receptor (pIgR) which was reportedly involved in single
      nucleotide polymorphism (SNP) of Japanese IgAN patients.

PMID- 21865696
TI  - Reactive arthritis induced by tonsillitis: a type of 'focal infection'.
AB  - OBJECTIVE: The clinical manifestation of reactive arthritis (ReA ) induced by
      tonsillitis is demonstrated. METHODS: Medical records of 21 patients with ReA
      induced by tonsillitis were analyzed. RESULTS: Nine male and 12 female patients
      were recorded. The mean age was 31.7 years ranging from 20 to 51 years. The mean
      duration of arthritis was 29.8 months (2 weeks to 10 years). Acute or recurrent
      origoarthritis involved in ankle, knee and sternoclavicular joints associated
      with Achilles tendon enthesitis were demonstrated. Thirteen of 21 (62%) patients
      were demonstrated positive for ASO and/or ASK. Group A streptococcus was
      demonstrated in 12 of 21 (57.1%) patients and other bacteria were demonstrated by
      culture of tonsillar swab or from resected tonsillar microabscess. No bacteria
      was demonstrated in synovial fluid from 3 patients. Rheumatoid factor was
      demonstrated only in 2 of 21 patients. HLA-B39 and BW61 (B40) were significantly
      demonstrated in 5 and 7 patients (p=0.0004, 0.0006, respectively) compared with
      those of healthy controls. All patients were treated with antibiotics and
      nonsteroidal anti-inflammatory drugs (NSAIDs). Eight of 21 patients underwent
      tonsillectomy. Arthritis ceased after the treatments and no recurrence was found.
      DISCUSSION: Sterile inflammatory arthritis induced by tonsillitis was cured by
      resection of the microabscess in the tonsils. Therefore, ReA induced by
      tonsillitis is one form of 'focal infection'.

PMID- 21865697
TI  - Tonsil-related skin diseases and possible involvement of T cell co-stimulation in
      chronic focal infection.
AB  - Some inflammatory skin diseases are known to be related to tonsil focal infection
      at their onset. Administration of antibiotics is adequate treatment in most acute
      or subacute cases. However, chronic focal infections in the tonsils could cause
      chronic skin diseases like pustulosis palmaris et plantaris (PPP), and it is our
      frequent experience that tonsillectomy leads to a dramatic and persistent
      improvement of PPP skin lesions. The expression of inducible co-stimulator
      (ICOS), a co-stimulatory receptor on activated T cells, was significantly higher
      in tonsil tissues from PPP patients than in tonsil tissues from non-PPP patients.
      Moreover, ICOS expression in tonsil tissues from 3 patients with psoriasis
      vulgaris that was strongly suspected to be related to tonsil focal infection was
      also high, suggesting that the activation of T cells via ICOS costimulation in
      focal infections likely triggers inflammation associated with tonsil-related skin
      diseases. PPP is notable today for paradoxically induced skin lesions in patients
      treated with TNF-alpha antagonists for rheumatoid arthritis, Crohn's disease,
      psoriasis and psoriatic arthritis. It is important to clarify the immunological
      milieu in PPP not only for the treatment approach but also for understanding
      these unexpected reactions.

PMID- 21865698
TI  - Clinical outcome of tonsillectomy for palmoplantar pustulosis and etiological
      relationship between palmoplantar pustulosis and tonsils.
AB  - Palmoplantar pustulosis (PPP) is famous for causing typical tonsillar focal
      diseases. Clinical improvement of PPP rash after tonsillectomy was seen in 109
      (94%) of 116 patients by subjective self-assessment, and 52 (88%) of 59 patients
      by objective Palmoplantar Pustulosis Area and Severity Index (PPPASI) scoring.
      Flow-cytometric analyses revealed that expression of activation markers (CD25 and
      HLA) class II increased on tonsillar T cells from PPP and IgAN patients.
      Moreover, expressions of skin-homing receptors (CLA and CCR6) increased on
      tonsillar T cells from PPP patients. In addition, the expressions were enhanced
      by stimulation of indigenous bacteria. Moreover, those expressions also increased
      in peripheral T cells, and decreased after tonsillectomy. Immunohistchemical
      analyses revealed that the ligands of those receptors (E-selectin and chemokine
      ligand 20) were expressed in lesions of skin. On the basis of our findings,
      migration of tonsillar T cells on which several homing receptors express by
      hyperimmune response against indigenous bacteria have a critical role in the
      pathogenesis of tonsillar focal diseases.

PMID- 21865699
TI  - Triggering role of focal infection in the induction of extra-palmoplantar lesions
      and pustulotic arthro-osteitis associated with palmoplantar pustulosis.
AB  - Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by
      sterile pustules predominantly involving the palms and soles of middle-aged
      women. Whether PPP is the acral type of pustular psoriasis or a distinct entity
      has long been discussed; however, the clinical features of PPP are really
      heterogeneous and different between Asians and Caucasians, which may depend on
      the race with backgrounds of different HLAs. PPP is closely related with
      psoriasis, but considered to be a distinct entity in Japan. Although the
      pathogenesis of PPP is still poorly understood, PPP is a representative skin
      disorder showing a close relationship with focal infections such as tonsillitis,
      chronic sinusitis, and dental infection. In particular, tonsillitis often
      triggers or deteriorates PPP. In Japanese patients, regions other than the palms
      and soles are occasionally affected manifesting scaly erythemas which resemble
      psoriasis, and solitary pustules are also seen. Some of these extra-palmoplantar
      lesions are induced by the Koebner phenomenon or occur after focal infections.
      Further, arthralgia is also induced on the sternum, clavics, sacroiliac joints,
      and upper ribs following focal infections. This paper makes a focus on the
      triggering role of focal infection in the induction of extra-palmoplantar lesions
      as well as arthralgia (putulotic arthro-osteitis).

PMID- 21865700
TI  - Role of biofilms in chronic inflammatory diseases of the upper airways.
AB  - The objective of our studies was to document the presence of bacterial biofilms
      in recurrent and chronic infectious diseases of the upper airways (UA)
      (adenoiditis, tonsillitis, chronic rhinosinusitis) and to assess the association
      between the presence of biofilm and the maintenance of a chronic inflammation.
      METHODS: 16 surgical samples of tonsils and adenoids from patients with UA
      infections and 24 samples of ethmoid mucosa from patients who underwent
      endoscopic sinus surgery for chronic rhinosinusitis (CRS) were cultured using
      conventional methods and subjected to scanning electron microscopy (SEM) to
      detect evidence of biofilm. RESULTS: Bacterial biofilms were observed in 57.5% of
      chronically infected UA mucosa; in 41.7% of ethmoid mucosa of CRS patients they
      were significantly (p<0.001) associated with a marked destruction of ciliated
      epithelium. DISCUSSION: Our studies confirm that biofilm formation plays a role
      in UA infections, it not only explains the resistance of these infections to
      antibiotic therapy, but also represents an important element that contributes to
      the maintenance of a chronic inflammatory reaction.

PMID- 21865701
TI  - Regulation of microbiota by antimicrobial peptides in the gut.
AB  - The antimicrobial peptide is one of major effectors of the innate immunity, and
      is common in the entire multicellular organisms. In mammals, one family of
      antibacterial peptide named defensins plays a central role in host defense,
      especially in the epithelial surface such as oral cavity, skin and the intestine.
      Recently, the importance of the antimicrobial peptides has been widely
      recognized. The epithelium of the gut is a largest surface that is exposed to
      various pathogens in the environment. It is the Paneth cells that produce
      antimicrobial peptides, alpha-defensins in the small intestine. Paneth cells
      contribute to mucosal innate immunity by sensing bacteria and releasing
      microbicidal activities mostly from activated alpha-defensins. In mice, alpha
      defensins, named cryptdins, consisted of six major isoforms (cryptdin-1 to
      cryptdin-6), and among those cryptdin-4 is the most microbicidal, suggesting that
      cryptdin-4 has a pivotal role in innate immunity. Paneth cell alpha-defensins
      have selective activities against commensal bacteria which may be associated with
      compositions of intestinal microbiota in vivo and homeostasis of the entire
      intestine. In addition, Paneth cell alpha-defensins appeared to be regulated
      topographically to control intestinal integrity.

PMID- 21865702
TI  - Evidence of the local immune status in the human larynx.
AB  - We have studied the presence of local immunity in the larynx and its role and
      development of laryngeal glands in the human larynx. The local immune status in
      laryngeal secretion or related tissue specimens from the laryngeal ventricle was
      examined and the results were analyzed between individuals with or without head
      and neck cancer. Laryngeal secretions or mucosal tissue specimens were obtained
      during the microscopic laryngeal surgery or at the time of the surgery of the
      larynx. The laryngeal secretion contained immunological factors such as IgG, IgM,
      IgA or secretory IgA (SIgA). The mean level of SIgA of the mucosal tissue was low
      in patients with the benign laryngeal disease and considerably decreased in
      patients with previous radiation therapy. The level of SIgA in the laryngeal
      secretion closely correlated to the level of SIgA in the mucosal tissue. From the
      present study, we confirmed the actual presence of local immune function in the
      human larynx. Furthermore, the local immune status is affected by either the
      presence of malignancy or the treatment to the larynx such as radiation.

PMID- 21865703
TI  - Short review on sublingual immunotherapy for patients with allergic rhinitis:
      from bench to bedside.
AB  - Sublingual immunotherapy has been considered to be a painless and effective
      therapeutic treatment for allergic rhinitis, and is known as type 1 allergy of
      the nasal mucosa. So far, its mechanism of action has been elucidated employing
      peripheral blood serum and lymphocytes in an antigen-specific fashion. Because of
      the limitations in sampling human materials, there is still controversy among
      many reports between clinical efficacy and laboratory data. Therefore, its
      mechanism of action needs to be investigated further by using promising animal
      models such as rodents and monkeys. Bearing this in mind, in our present study,
      we successfully constructed an effective murine model for sublingual
      immunotherapy in allergic rhinitis in which mice were administered ovalbumin
      (OVA) sublingually followed by intraperitoneal sensitization and nasal challenge.

PMID- 21865704
TI  - Differential properties of mucous glycoproteins produced by allergic inflammation
      and lipopolysaccharide stimulation in rat nasal epithelium.
AB  - To examine the differential properties of mucous glycoproteins, we produced
      hyperplastic and metaplastic changes in goblet cells of rat nasal epithelium by
      intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats, and by
      intranasal lipopolysaccharides (LPS) instillation. The epithelial mucosubstance
      was quantitatively examined by AB-PAS and lectin histochemistry. The newly
      produced mucin after OVA challenge or LPS instillation contained a high amount of
      sulfomucin and a low amount of neutral glycoprotein: LPS-induced mucin contained
      more sulfomucin (70.1% of total) and less neutral glycoprotein (8.6%) than OVA
      induced mucin (sulfomucin 33.6%, neutral glycoprotein 41.8%). Four of the
      lectins, PNA, MAL II, SNA, UEA I, stained some of the mucosubstance, indicating
      the presence of galactose-N-acetylgalactosamine, alpha2,3-linked and alpha2,6
      linked sialic acid-galactose, and fucose residues. After LPS instillation, the
      reactivity was higher for galactose-N-acetylgalactosamine (64.8% of total) and
      alpha2,3-linked sialic acid-galactose (75.8%) than after saline instillation (3.5
      and 19.1%, respectively) or OVA challenge (5.8 and 32.3%). A 2-fold increase in
      mucin mRNA (rat Muc5ac) expression was induced after LPS instillation or OVA
      challenge. These results indicate that mucin mRNA expression increases similarly
      after LPS instillation or OVA challenge, however, carbohydrate compositions of
      newly produced mucin are different between the two groups.

PMID- 21865705
TI  - Nasal-associated lymphoid tissue immunity and vaccine development.
AB  - Nasal vaccination is an effective therapeutic regimen for preventing upper
      respiratory infectious diseases. In the development of nasal vaccine, an
      appropriate adjuvant is required. In the present study, we examined the efficacy
      of fms-like tyrosine kinase receptor-3 ligand (Flt3L) as a mucosal adjuvant. Mice
      were immunized intranasally with Flt3L and P6 protein of nontypeable Haemophilus
      influenzae (NTHi), and P6-specific immune responses were examined. In addition,
      NTHi challenges were performed and the level of NTHi was quantified in nasal
      washes. Nasal vaccination with P6 and Flt3L induced an increase in the number of
      dendritic cells in nasal-associated lymphoid tissue. P6-specific nasal wash
      immunoglobulin (Ig)A and serum IgG titers were elevated significantly after nasal
      immunization. Enhanced NTHi clearance from the nasopharynx was also observed.
      These results indicate the potential of Flt3L as an effective mucosal adjuvant
      and suggest that nasal vaccination with P6 and Flt3L might be an effective
      regimen for the induction of NTHi-specific protective immunity.

PMID- 21865706
TI  - Intranasal therapy with CpG DNA alone for the control of allergic rhinitis.
AB  - Many people all over the world suffer from allergic rhinitis, induced by Th2
      responses. CpG DNA, containing a central unmethylated C-G dinucleotide, promotes
      Th1 responses. Consequently, Th2 responses decrease. Systemic administration of
      CpG DNA could attenuate allergic rhinitis. However, studies investigating the
      effects of intranasal therapy with CpG DNA alone on allergic rhinitis are rare.
      Therefore, we estimated the effectiveness of intranasal administration of CpG DNA
      alone on allergic rhinitis compared with intradermal administration. Mice were
      sensitized intraperitoneally and challenged intranasally with Cryptomeria
      japonica. Therapy with CpG DNA alone was performed during the challenge, either
      intranasally or intradermally. Immunologic variables and nasal symptoms were
      examined. Intranasal administration of CpG DNA alone significantly reduced nasal
      symptoms, nasal eosinophilia, and the levels of IgE as well as IL-5 production
      from nasal lymphocytes and splenocytes, although intradermal administration of
      CpG DNA alone did not show a significant reduction. This study demonstrated that
      CpG DNA has effects not only on splenocytes but also on nasal lymphocytes, and
      that the intranasal administration of CpG DNA alone is useful in the management
      of allergic rhinitis.

PMID- 21865707
TI  - Airway bacterial interactions and impact on host immune responses.
AB  - The dynamic interactions of the major respiratory microbial pathogens are
      complex. An understanding of the impact on naturally acquired immune responses to
      respiratory polymicrobial commensal bacteria is slowly evolving. Maintaining a
      micro-floral balance and the host's ability to respond to imbalances associated
      with disease is critical. Studies of acquired immune responses have found that
      both antibody and cellular immune responses are suppressed by the presence of
      multiple bacteria when compared with colonization by the single microbe. Microbes
      interact with the mucosal epithelium through a range of receptor-ligand
      interactions, including interactions with Toll-like receptors and adhesion
      molecules. Regulation of the inflammatory response associated with commensal
      colonization suggests a possible role for Treg cells in controlling the upper
      airway responses to bacterial microflora with both bacteria-bacteria and bacteria
      host interactions affecting colonization and immune responses.

PMID- 21865708
TI  - Protection of pneumococcal infection by maternal intranasal immunization with
      pneumococcal surface protein A.
AB  - Streptococcus pneumoniae is one of the important causative pathogens for both
      upper and lower respiratory tract infections during childhood. The current study
      was designed to evaluate the protection against fatal pneumococcal infections
      during the infant period by maternal immunization with pneumococcal surface
      protein A (PspA). Four-week-old females BALB/c mice were immunized with PspA and
      cholera toxin B (CTB) intranasally twice a week for 3 weeks. After mating, the 10
      day-old offspring of these mice were intraperitoneally (i.p.) infected with S.
      pneumoniae to evaluate survival. Anti-PspA-specific IgG antibody was induced in
      the sera of mother and offspring. The survival times to death after systemic
      fatal pneumococcal infections were significantly extended among offspring
      delivered from PspA-immunized mothers than the controls. Current findings suggest
      that maternal intranasal immunization with PspA is an attractive procedure
      against pneumococcal infections in early childhood.

PMID- 21865710
TI  - Immunologic impact of tonsillopharyngitis associated with group A streptococci.
AB  - While very common clinically, group A streptococcal infections of the upper
      respiratory tract remain incompletely understood. Vital to clarifying these
      incompletely answered questions is the understanding of the immune responses
      associated with infection and the enigmatic 'carrier state'. An important aspect
      of this is understanding the differences between an immune response and a
      protective immune response. Several of these concerns are discussed.

PMID- 21865709
TI  - Heat-shock protein ClpL/HSP100 increases penicillin tolerance in Streptococcus
      pneumoniae.
AB  - Penicillin resistance and tolerance has been an increasing threat to the
      treatment of pneumococcal pneumoniae. However, no penicillin tolerance-related
      genes have been claimed. Here we show that a major heat shock protein ClpL/HSP100
      could modulate the expression of a cell wall synthesis enzyme PBP2x, and
      subsequently increase cell wall thickness and penicillin tolerance in
      Streptococus pneumoniae.

PMID- 21865711
TI  - Influence of Waldeyer's ring hypertrophy on snoring and sleep apnea.
AB  - Severe adenotonsillar hypertrophy can be the main cause of nocturnal respiratory
      affections, as confirmed by the improvement of symptoms seen after
      adenotonsillectomy. Unsuccessful surgical treatment can be due to craniofacial
      morphological alterations. Hypotony of the pharyngeal muscles could also be
      responsible together with tonsil hypertrophy. In our study, we enrolled 125
      patients (87 males and 38 females), aged from 3 to 8 years, suffering from
      chronic snoring. All the patients underwent adenotonsillectomy. The follow-up was
      carried out at 2, 4 and 6 months after the operation. Snoring and nocturnal
      apneas were no longer present in almost all the patients. Overnight
      polysomnography remains the gold standard diagnostic test for obstructive sleep
      apnea syndrome, but its feasibility in clinical practice is debated.
      Rhinomanometry, which gives an objective evaluation of ventilatory nasal
      function, acoustic rhinometry, which measures the cross-section in fixed nasal
      areas, and nasal mucociliary transport time can be considered useful tests to
      evaluate the cause of respiratory obstruction.

PMID- 21865712
TI  - Tonsils diseases, past, present and future and the impact in clinical practice in
      Brazil.
AB  - A simplified review of the research carried out in Brazil on tonsils is
      presented: histopathological findings in children's tonsils with allergy, the
      detection of Epstein-Barr virus, herpes virus (SV1 e SV2, HHV8) and the
      correlation between tonsil hypertrophy and recurrence of infection is discussed.
      The role of allergy in children with tonsillitis and/or tonsil and adenoid
      hypertrophy are analyzed. After participating in the Tonsils Symposium in 1991,
      the knowledge of tonsils morphology, immunology and histopathology increased,
      triggering a change in clinical practice in Brazil.

PMID- 21865713
TI  - Clinical scoring system of acute pharyngotonsillitis.
AB  - OBJECTIVES: The aim of this study was to evaluate clinical outcomes of acute
      pharyngo-tonsillitis by a scoring system and the impact of causative pathogens.
      METHODS: The patients with acute pharyngotonsillitis were evaluated for causative
      pathogens and her clinical symptoms and pharyngotonsillar finding by a clinical
      scoring system were assessed. RESULTS: Streptocococcus pyogenes were identified
      at 13.6%. Thirty-one viruses were also identified by PCR. The numbers of total
      white blood cells and the levels of C-reactive protein showed a significant
      positive correlation with clinical scores (p<0.001) and were significantly higher
      in cases with S. pyogenes. The clinical scores rapidly improved after the
      antimicrobial treatments in moderate cases and severe cases. CONCLUSION: A
      clinical scoring system represents the severity of acute pharyngotonsillitis and
      is useful for evaluating clinical course of the illness.

PMID- 21865714
TI  - Clinical guideline on adenotonsillectomy: the Italian experience.
AB  - Five years after publishing the document on 'The clinical and organizational
      appropriateness of tonsillectomy and adenoidectomy' in 2003, a multidisciplinary
      group of experts came together again to update this document and to publish a
      guideline with grading of evidences and recommendations. Major revisions of the
      previous document were addressed to: (1) the diagnosis and indications for
      adenotonsillectomy in presence of OSAS in children, (2) the analysis of
      advantages of new surgical techniques in terms of effectiveness, costs or the
      risk of postsurgery bleeding and recurrences, and (3) the efficacy of
      perioperative management in reducing the incidence and duration of post-operative
      events. In fact, in the last years, a relevant number of evidence became
      available on the above-mentioned items making the need for a continuing updating
      of guidelines tangible. As a premise to the guideline, it is stressed how the
      previous document impact was prominent: the decrease of total number of
      tonsillectomy in Italy was evident and accompanied by a decrease of variations in
      the regional rates. Besides the document contributed to strengthen the
      multidisciplinary collaboration, especially between pediatricians and
      otorhinolaryngologists, and to divulge the Evidence-Based Medicine culture.

PMID- 21865715
TI  - Diversity of mucosal immune responses in upper respiratory organs and its
      application for mucosal vaccine.
AB  - Mucosal vaccine has been considered a promising strategy to prevent upper
      respiratory infections. As the immunization routes to induce mucosal immune
      responses, oral, intranasal, and sublingual immunizations are proposed for
      clinical application. Recently, it has been reported that transcutaneous
      immunization is also capable of inducing mucosal immune responses. However, it
      still remains unclear which route is the most effective to induce mucosal immune
      responses in upper respiratory organs. In order to investigate the differences in
      the immune responses among several mucosal immunizations, mice were immunized
      with phosphorylcholine (PC) together with cholera toxin (CT) as mucosal adjuvant
      intranasally, sublingually, and transcutaneously, and the mucosal as well as
      systemic immune responses were compared. PC-specific IgA antibody titers in
      saliva and nasal wash were increased by intaranasal as well as sublingual
      immunization to the same levels. However, IgE levels induced by mucosal
      immunization were remarkably reduced by sublingual immunization. Transcutaneous
      immunization increased mucosal IgA responses, although the levels were lower than
      those induced by intaranasal and sublingual immunization. Those results suggest
      that sublingual immunization might be superior to the other immunizations in
      inducing PC-specific mucosal immune responses in upper respiratory tract.

PMID- 21865716
TI  - Nasal submucosal administration of antigen-presenting cells induces effective
      immunological responses in cancer immunotherapy.
AB  - Human NKT cells are known to have strong antitumor activities and to be activated
      by specific ligand, alpha-galactosylceramide (alphaGelCer). We examined the
      migration pattern of alphaGalCer-pulsed DCs and the immune responses after
      administration by different routes. DCs injected into nasal submucosa quickly
      migrated to the lateral neck lymph rather than the lateral lymph nodes. The
      absolute number of NKT cells and the IFN-gamma-producing cells increased in
      peripheral blood after injection of the DCs into nasal submucosa. We conducted a
      phase I study with alphaGalCer-pulsed DCs administered in nasal submucosa of
      patients with head and neck cancer, and evaluated safety and feasibility. The
      results showed that nasal submucosal administration of alpha-GalCer-pulsed DCs
      was safe and a smaller number of these DCs could exhibit significant immune
      responses and some positive clinical effects. In additional study, the use of the
      intra-arterial infusion of activated NKT cells and the submucosal injection of
      alpha-GalCer-pulsed DCs has been shown to induce significant antitumor immunity
      and had beneficial clinical effects in the management of advanced head and neck
      squamous cell carcinoma. The NKT cell-based cancer immunotherapy may be helpful
      in management of head and neck cancer and needs to be explored in further detail.

PMID- 21865717
TI  - Respiratory syncytial virus infection and the tight junctions of nasal epithelial
      cells.
AB  - Respiratory syncytial virus (RSV) primarily infects upper respiratory tract
      cells, mainly nasal epithelial cells. The tight junctions of nasal epithelial
      cells are thought to perform important innate immune function against foreign
      materials including respiratory viruses. We investigated in vitro the
      relationship of RSV infection and the tight junctions of primary nasal epithelial
      cells which had been transfected with human telomerase reverse transcriptase
      (hTERT) to prolong cell life. Nasal epithelial cells developed tight junctions
      when cultured in medium containing fetal bovine serum, and these cells showed
      apparent resistance to RSV infection compared to control cells. RSV could infect
      these cells from apical but not basolateral side, suggesting that only apical
      side possess RSV receptor or a mechanism for absorbing RSV particles.
      Importantly, RSV infection of the cells enhanced the expression of tight junction
      proteins occludin, claudin-4 and ZO-1. These findings suggest that RSV infection
      induces polarity in the infected cells. This polarity could facilitate cellular
      secretion of propagated RSV, thereby spreading the infection.

PMID- 21865718
TI  - A novel immune evasion mechanism of LMP-1, an EBV-primary oncogene, in
      nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor. Viruses
      that are associated with malignant transformation have evolved unique mechanisms
      to interfere with this interaction to evade antiviral T cell responses. EBV
      exploits many immune evasive strategies to successfully establish a latent
      infection in B cells. CD8+ T cell responses to LMP-1 are generally very low and
      rarely detected in healthy virus carriers. Activation of the NF-kB pathway by EBV
      LMP-1 leads to an upregulation of the MHC class I antigen-processing pathway.
      Paradoxically, LMP-1itself induces a subdominant CD8+ T cell response and appears
      to have evolved to avoid immune recognition. An expression of LMP-1 in human
      cells enhanced the trans-presentation of CD8+ T cell epitopes; however, cis
      presentation of LMP-1-derived epitopes was severely impaired. Deletion of the
      first transmembrane domain of LMP-1, which prevented self-aggregation,
      significantly enhanced the cis-presentation of T cell epitopes from this protein,
      whereas it lost its ability to upregulate trans-presentation. These results
      delineate a novel mechanism of immune evasion, which renders a virally encoded
      oncogene inaccessible to the conventional MHC class I pathway limiting its cis
      presentation.

PMID- 21865719
TI  - Otitis media and tonsils--role of adenoidectomy in the treatment of chronic
      otitis media with effusion.
AB  - Innate immunity involves the first line of the mucosal defense system.
      Homeostatic defense of the middle ear and Eustachian tube is maintained in part
      by molecules related to the innate immunity. The middle ear and tonsils are the
      organs related to the innate immunity. Recent attention has focused on the
      possibility that chronic otitis media and adenotonsillitis may represent a
      chronic infective state such as evidenced in conditions secondary to biofilms or
      small colony variants. The role of biofilms in the persistence of chronic mucosal
      based ENT-related infections was first recognized in otitis media and
      adenotonsillitis. The efficacy of adenotonsillectomy on otitis media with
      effusion (OME) has been demonstrated by several randomized and controlled
      studies. It was speculated that tonsil and adenoid may play a role as an
      infectious focus to OME. In summary, patients suffering from recurrent or chronic
      OME may benefit from adenoidectomy due to the removal of an infectious source in
      the nasopharynx rather than the removal of a large adenoidal mass.

PMID- 21865720
TI  - Otitis media and immunological alterations of Waldeyer's ring.
AB  - In the literature, correlations between adenoids and middle ear disorders have
      been widely discussed over the years. Adenoids fundamentally influence
      inflammation/ infections of the middle ear through 3 factors: obstructive,
      inflammatory/infective, and immunologic. The authors carefully analyze each of
      these factors reviewing the opinion of the most important researches in the
      field. The important role of immunological (T cells and Ig), infective
      (microorganisms and bacterial biofilms) and allergic factors as predisposing
      factors for otitis media leads one to consider the importance of a medical
      treatment oriented to correction of the infective and immunological disorders in
      children with OM, without adenoids hypertrophy.

PMID- 21865721
TI  - Role of nontypeable Haemophilus influenzae in otitis media and chronic
      obstructive pulmonary disease.
AB  - In both infants and adults, infections with non-typeable Haemophilus influenzae
      (NTHI) results in morbidity and mortality. NTHI strains are the leading cause of
      bacterial otitis media infections (both acute and recurrent) in young children
      and are also responsible for chronic obstructive pulmonary disease (COPD)
      exacerbations in current and former smokers. The realization that NTHI causes
      serious infections in humans has generated interest in the study of the
      pathogenesis associated with this bacterium and also stimulated considerable
      efforts towards the evaluation of candidate vaccines that will elicit protective
      immunity. As NTHI is exclusively a human pathogen and has not been associated
      with any diseases in other mammals, special efforts have been necessary to
      establish animal models of NTHI infection to generate useful data on the
      pathogenesis of infection and efficacy of potential vaccines. This article
      provides a brief summary of the role of NTHI in disease and the work that has
      been accomplished by us and several other investigators.

PMID- 21865722
TI  - Recent changes in nasopharyngeal flora of children in Japan.
AB  - We investigated the relationship between nasopharyngeal flora of pediatric
      patients and antibiotic consumption in a local community in Japan between 2000
      and 2009 retrospectively. There was a clear relationship between the lower annual
      consumption rate of cephalosporins and the lower annual prevalence of non
      susceptible strains of Streptococcus pneumoniae (SP). High prevalence of BLNAR
      (beta-lactamase nonproducing ampicillin-resistant Haemophilus influenzae) has
      been one of the bacteriological features of Japan.

PMID- 21865723
TI  - Effectiveness of theta-burst repetitive transcranial magnetic stimulation for
      treating chronic tinnitus.
AB  - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS), a noninvasive
      method for altering cortical excitability, is becoming a therapeutic strategy in
      auditory research institutions worldwide. Application of inhibiting rTMS on these
      overactive cortical regions can result in effective tinnitus suppression. The aim
      of this study is to investigate the efficacy of theta-burst rTMS in patients with
      chronic tinnitus. STUDY DESIGN: Parallel randomized control study. SETTING:
      Tertiary referral center. PATIENTS: We enrolled 2 female and 20 male patients in
      this study. The evaluative tools included tinnitus frequency- and loudness
      matching, tinnitus questionnaires (TQ), and the Tinnitus Handicap Inventory
      (THI). METHODS: The orthogonal projection of the auditory cortex on the scalp was
      focalized. A figure-eight coil was placed on the surface of the skull over the
      targeted region with the intensity setting at 80% of the resting motor threshold.
      We delivered 900 pulses of theta-burst rTMS daily for 10 business days. MAIN
      OUTCOME MEASURES: Nine of twelve patients (75%) in the active-stimulation group
      reported tinnitus suppression following treatment with rTMS. The treatment led to
      reductions of 8.58 and 8.33 in the mean TQ global and THI scores, respectively.
      Tinnitus loudness also decreased significantly after delivering rTMS. RESULTS:
      Descriptive analysis of the TQs revealed that patients experienced significant
      improvements in emotional distress levels and somatic symptoms. CONCLUSIONS: Our
      preliminary results demonstrate that theta-burst rTMS treatments offer a method
      of modulating tinnitus. Patients could benefit from emotional improvements, even
      more than auditory perceptive relief. Further studies are needed to establish a
      standard protocol and to clarify nervous propagation along the auditory and
      psychological projection following treatment with rTMS.

PMID- 21865724
TI  - Effects of high blood flow and high pre-dilution replacement fluid rates on small
      solute clearances in hemofiltration.
AB  - BACKGROUND/AIMS: In pre-dilution hemofiltration (HF), solute clearance is less
      than the HF rate. While the amount of this loss is predictable, it has not been
      validated in high-volume HF associated with high blood flow rates. METHODS: Using
      isovolemic pre-dilution HF, we studied small solute clearances using combinations
      of blood flow (Q(B); 150, 250, 350, 450 ml/min) and replacement fluid (RF) flow
      (Q(RF); 2, 4, 6 l/h) to determine clearance losses we entitled 'measured
      efficiency' (E(M)). E(M) was compared to predicted efficiency (E(P)) = (Q(B)/Q(B)
      + Q(RF)). RESULTS: Pre-dilution produced E(M) values of 61-93%. Increases in Q(B)
      for any Q(RF) and decreases in Q(RF) for any Q(B) increased E(M) over a wide
      range of Q(B) and Q(RF). E(P) was equivalent to E(M). CONCLUSION: In high-volume
      pre-dilution HF, E(P) can be used to determine E(M) across a broad range of Q(B)
      and Q(RF) values. Higher Q(RF) requires higher Q(B) to minimize the attenuating
      effects of pre-dilution on clearance.

PMID- 21865725
TI  - Celastrol inhibits breast cancer cell invasion via suppression of NF-KB-mediated
      matrix metalloproteinase-9 expression.
AB  - BACKGROUND/AIMS: Metastasis is one of the main causes of death for patients with
      malignant tumors. Induction of matrix metalloproteinase (MMP)-9 is particularly
      important for the invasiveness of various cancer cells. Celastrol, a triterpenoid
      isolated from the traditional Chinese medicine, is known to inhibit the
      proliferation of a variety of tumor cells, including leukemia, glioma, prostate
      and breast cancer cells. In this study, we investigated the effect of celastrol
      on the migration and invasion of human breast carcinoma cells. RESULTS: We
      observed that celastrol suppressed phorbol 12-myristate 13-acetate (PMA)-induced
      invasion and migration of MCF-7 cells. We also found that celastrol inhibited PMA
      induced MMP-9 expression at both the mRNA and the protein levels, and the
      proteolytic activity of MMP-9 in MCF-7 cells. Our results revealed that celastrol
      inhibited the transcriptional activity of MMP-9 by suppression of the DNA binding
      activity of NF-kappaB in the MMP-9 promoter, and inhibited degradation of
      IkappaBalpha and nuclear translocation of NF-kappaB. CONCLUSION: These results
      indicate that celastrol inhibits NF-kappaB-mediated MMP-9 expression, resulting
      in suppression of breast cancer cell invasion and migration that is induced by
      PMA. Celastrol is a potential agent for clinical use in preventing the invasion
      and metastasis of human malignant breast tumors.

PMID- 21865726
TI  - Differential gene regulation under altered gravity conditions in follicular
      thyroid cancer cells: relationship between the extracellular matrix and the
      cytoskeleton.
AB  - Extracellular matrix proteins, adhesion molecules, and cytoskeletal proteins form
      a dynamic network interacting with signalling molecules as an adaptive response
      to altered gravity. An important issue is the exact differentiation between real
      microgravity responses of the cells or cellular reactions to hypergravity and/or
      vibrations. To determine the effects of real microgravity on human cells, we used
      four DLR parabolic flight campaigns and focused on the effects of short-term
      microgravity (22 s), hypergravity (1.8 g), and vibrations on ML-1 thyroid cancer
      cells. No signs of apoptosis or necrosis were detectable. Gene array analysis
      revealed 2,430 significantly changed transcripts. After 22 s microgravity, the F
      actin and cytokeratin cytoskeleton was altered, and ACTB and KRT80 mRNAs were
      significantly upregulated after the first and thirty-first parabolas. The COL4A5
      mRNA was downregulated under microgravity, whereas OPN and FN were significantly
      upregulated. Hypergravity and vibrations did not change ACTB, KRT-80 or COL4A5
      mRNA. MTSS1 and LIMA1 mRNAs were downregulated/slightly upregulated under
      microgravity, upregulated in hypergravity and unchanged by vibrations. These data
      indicate that the graviresponse of ML-1 cells occurred very early, within the
      first few seconds. Downregulated MTSS1 and upregulated LIMA1 may be an adaptive
      mechanism of human cells for stabilizing the cytoskeleton under microgravity
      conditions.

PMID- 21865727
TI  - 4-aminopyridine induces apoptosis of human acute myeloid leukemia cells via
      increasing [Ca2+]i through P2X7 receptor pathway.
AB  - 4-AP, a voltage-gated potassium channel blocker, was identified to exert critical
      pro-apoptotic properties in various types of cancer cells. The present study aims
      to explore the effect of 4-AP on the apoptosis of human AML cells and the
      underlying mechanism. We found 4-AP inhibited the proliferation and induces
      apoptosis in both AML cell lines and primary cultured human AML cells. The
      apoptosis of AML cells after 4-AP treatment was further confirmed by the
      disruption of mitochondrial membrane potential (MMP) and activation of caspase 3
      and 9. 4-AP inhibited Kv currents in NB(4), HL-60 and THP-1 cells. Furthermore, 4
      AP induced significant increment in [Ca(2+)](i), which were inhibited by KN-62, a
      specific blocker of P(2)X(7) receptors. KN-62 also abrogated 4-AP induced
      apoptosis. Knockdown of P(2)X(7) receptor by small interfering RNA blocked the
      effect of 4-AP. Conclusively, this study indicated that 4-AP promotes apoptosis
      in human AML cells via increasing [Ca(2+)](i) through P(2)X(7) receptor.

PMID- 21865728
TI  - Comparative evaluation of different cell lysis and extraction methods for
      studying benzo(a)pyrene metabolism in HT-29 colon cancer cell cultures.
AB  - Lysis and extraction of cells are essential sample processing steps for
      investigations pertaining to metabolism of xenobiotics in cell culture studies.
      Of particular importance to these procedures are maintaining high lysis
      efficiency and analyte integrity as they influence the qualitative and
      quantitative distribution of drug and toxicant metabolites in the intra- and
      extracellular milieus. In this study we have compared the efficiency of different
      procedures viz. homogenization, sonication, bead beating, and molecular grinding
      resin treatment for disruption of HT-29 colon cells exposed to benzo(a)pyrene
      (BaP), a polycyclic aromatic hydrocarbon (PAH) compound and a suspected colon
      carcinogen. Also, we have evaluated the efficiency of various procedures for
      extracting BaP parent compound/metabolites from colon cells and culture media
      prior to High Performance Liquid Chromatography (HPLC) analyses. The extraction
      procedures include solid phase extraction, solid-supported liquid- liquid
      extraction, liquid-liquid extraction, and homogeneous liquid- liquid extraction.
      Our findings showed that bead-beating in combination with detergent treatment of
      cell pellet coupled with liquid-liquid extraction yielded greater concentrations
      of BaP metabolites compared to the other methods employed. Our method
      optimization strategy revealed that disruption of HT-29 colon cells by a
      combination of mechanical and chemical lysis followed by liquid-liquid extraction
      is efficient and robust enough for analyzing BaP metabolites from cell culture
      studies.

PMID- 21865729
TI  - Resveratrol potentiates the cytotoxic oxidative stress induced by chemotherapy in
      human colon cancer cells.
AB  - The treatment of advanced colorectal cancer with 5-fluorouracil has two major
      problems: development of tumor resistance and toxicity toward normal tissues. The
      aim of this study was to investigate the possible advantages of combining 5
      fluorouracil (5-FU) with resveratrol (trans-3, 4', 5-trihydroxystilbene) for
      treating HT-29 and SW-620 colorectal carcinoma cell lines. Since combined
      treatment using 5-FU with resveratrol resulted in a significant decrease in long
      term cell survival, we investigated the possible basis of this synergistic
      interaction at a molecular level, focusing on oxidative stress as a possible
      mediator of cell death. Resveratrol established interactions with the
      mitochondria of cancer cells and induced an imbalance in cellular antioxidant
      activities, leading to a significant increase in the levels of both intracellular
      reactive oxygen species (ROS) and lipid peroxides. Combined treatment with
      resveratrol sensitized colon cancer cells to 5-fluorouracil, inducing a further
      increase in oxidative stress, which was linked to the inhibition of AKT and STAT3
      proteins, which are known to have oncogenic potential in colorectal carcinomas.

PMID- 21865730
TI  - TGFbeta-induced early activation of the small GTPase RhoA is Smad2/3-independent
      and involves Src and the guanine nucleotide exchange factor Vav2.
AB  - TGFbeta has been shown to induce short- and long-term actin reorganization
      controlled by Rho-GTPase signaling. A number of direct Smad target genes, rapidly
      activated by TGFbeta, have been previously reported to control the long-term Rho
      activation and actin reorganization. However, the molecular mechanisms that
      regulate the prompt stimulation of Rho GTPases by TGFbeta remain unknown. In the
      present study we report that TGFbeta rapidly stimulated RhoA and RhoB activation
      in JEG3 choriocarcinoma cells that lack endogenous Smad3. Inhibition of Smad2
      expression via siRNA-mediated silencing or by blocking its phosphorylation using
      the TbetaRI inhibitor SB431542 did not prevent the early RhoA/B activation by
      TGFbeta indicating that this effect is Smad2/3-independent. Pre-treatment of the
      cells with the general tyrosine kinase inhibitor Genistein blocked the TGFbeta
      induced early RhoA activation. In line with this finding, TGFbeta-stimulation
      resulted in a quick activation of the non-receptor tyrosine kinase Src, followed
      by activation of the guanine nucleotide exchange factor (GEF) Vav2. Inhibition of
      Src kinase by the selective inhibitor of the Src family tyrosine kinases PP2
      totally blocked the early TGFbeta-induced RhoA activation. Similarly, Vav2
      silencing via siRNA reduced the TGFbeta-induced RhoA activation implying that the
      rapid Src/Vav2 stimulation was effective in regulating RhoA activation. Our
      present findings provide for the first time a clear evidence for the role of Src
      and Vav2-GEF in the early Smad2/3-independent Rho activation by TGFbeta.

PMID- 21865731
TI  - Stimulation of murine intestinal secretion by daily genistein injections: gender
      dependent differences.
AB  - BACKGROUND/AIMS: The effect of daily injections with genistein (naturally
      occurring phytoestrogen) on intestinal chloride (Cl(-)) secretion was measured
      with Ussing chamber short circuit current (I(sc), MUA/cm(2)), in C57BL/6J male
      and female mice, using 600 mg/kg genistein/day (600G), 300 mg/kg genistein/day
      (300G), 150 mg/kg genistein/day (150G) or genistein-free vehicle control (0G) for
      1- or 2-weeks. METHODS AND RESULTS: Injecting with 600G elicited significant
      increases in basal I(sc) in females after 1-week (n70 MUA/cm(2), n=15, p < 0.05)
      and in males after 2-weeks (n80 MUA/cm(2), n=5, p < 0.05) compared to their 0G
      counterparts. Chloride-free ringer significantly reduced basal I(sc) by 65% in
      600G males and 72% in 600G females, suggesting that Cl(-) was the major anion
      comprising the genistein-stimulated secretion. The forskolin-stimulated (10 MUM)
      I(sc) was significantly inhibited by the CFTR chloride channel inhibitors,
      glibenclamide (500 MUM) and CFTR(inh)-172 (100 MUM) in 600G males and females,
      suggesting some contribution by genistein-dependent CFTR-mediated Cl(-)
      secretion. We found no associated changes in intestinal morphology, nor change in
      total CFTR protein with 600G. There was a 5% increase in apical/subapical ratio
      in 600G males compared to controls (no change in females). CONCLUSION: These data
      suggest that male and female mice both exhibit increased Cl- secretion with 600G,
      however, the mechanisms mediating this are gender-dependent.

PMID- 21865732
TI  - Downregulation of NaPi-IIa and NaPi-IIb Na-coupled phosphate transporters by
      coexpression of Klotho.
AB  - Klotho, a transmembrane protein, protease and hormone has been shown to exert a
      profound effect on phosphate metabolism. Klotho overexpression lowers and Klotho
      deficiency increases the plasma phosphate concentration, effects in part
      attributed to an inhibitory effect of Klotho on the formation of 1,25
      dihydroxycholecalciferol (1,25(OH) (2)D(3)), the active form of Vitamin D. Beyond
      that Klotho has been shown to decrease renal tubular phosphate transport more
      directly. The influence of Klotho on the plasma phosphate concentration
      contributes to the profound effect of Klotho on ageing and life span. The present
      study explored whether Klotho influences the major renal tubular (NaPi-IIa) and
      the major intestinal (NaPi-IIb) phosphate transporters. For functional analysis
      NaPi-IIa or NaPi-IIb were expressed in Xenopus oocytes both, without or with
      additional coexpression of Klotho and electrogenic phosphate transport was
      estimated from the phosphate-induced current (Ip). According to RT-PCR Klotho is
      expressed in the murine kidney and intestine. Coexpression of Klotho decreased Ip
      in both NaPi-IIa- and NaPi-IIb-expressing oocytes. Klotho decreased the maximal
      Ip without appreciably affecting the concentration required for halfmaximal Ip.
      Treatment of NaPi-IIa- or NaPi-IIb-expressing oocytes with Klotho protein
      similarly decreased Ip. In conclusion, Klotho down regulates both, renal (NaPi
      IIa) and intestinal (NaPi-IIb) phosphate transporters.

PMID- 21865733
TI  - ENaC channels in oocytes from Xenopus laevis and their regulation by xShroom1
      protein.
AB  - Shroom is a family of related proteins linked to the actin cytoskeleton. xShroom1
      is constitutively expressed in X. oocytes and is required for the expression of
      amiloride sensitive sodium channels (ENaC). Oocytes were injected with alpha,
      beta, and gamma mENaC and xShroom1 sense or antisense oligonucleotides. We used
      voltage clamp techniques to study the amiloride-sensitive Na(+) currents
      (INa((amil))). We observed a marked reduction in INa((amil)) in oocytes co
      injected with xShroom1 antisense. Oocytes expressing a DEG mutant beta-mENaC
      subunit (beta-S518K) with an open probability of 1 had enhanced INa((amil))
      although these currents were also reduced when co-injected with xShroom1
      antisense. Addition of low concentration (20 ng/ml) of trypsin which activates
      the membrane-resident ENaC channels led to a slow increase in INa((amil)) in
      oocytes with xShroom1 sense but had no effect on the currents in oocytes
      coinjected with ENaC and xShroom1 antisense. The same results were obtained with
      higher concentrations of trypsin (2 MUg/ml) exposed during 2.5 min. In addition,
      fluorescence positive staining of plasma membrane in the oocytes expressing
      alpha, beta and gamma mENaC and xShroom1 sense were observed but not in oocytes
      coinjected with ENaC and xShroom1 antisense oligonucleotides. On this basis, we
      suggest that xShroom1-dependent ENaC inhibition may be through the number of
      channels inserted in the membrane.

PMID- 21865734
TI  - Paracrine interaction between bone marrow-derived stem cells and renal epithelial
      cells.
AB  - BACKGROUND/AIMS: Renal tubular cells are the main target of ischemic insult
      associated with acute renal injury. Low oxygen and nutrient supplies result in
      ATP depletion, leading to cell death and loss of renal function. A possible
      mechanism by which bone marrow-derived cells support renal tissue regeneration
      relies on the capacity of mononuclear cells (BMMC), particularly mesenchymal stem
      cells (MSC), to secrete paracrine factors that mediate support for kidney
      regeneration. METHODS: BMMC/MSC and renal cells (LLC-PK(1) from pig and IRPTC
      from rat) were co-cultured under stressful conditions (ATP depletion and/or serum
      free starvation), physically separated by a microporous membrane (0.4 MUm), was
      used to determine whether bone marrow-derived cells can interact with renal cells
      in a paracrine manner. RESULTS: This interaction resulted in stimulation of renal
      cell proliferation and the arrest of cell death. MSC elicit effective responses
      in renal cells in terms of stimulating proliferation and protection. Such effects
      are observed in renal cells co-cultured with rat BMMC/MSC, an indication that
      paracrine mechanisms are not entirely species-specific. CONCLUSION: The paracrine
      action of BMMC/MSC was influenced by a renal cell stimulus released during
      stress, indicating that cross-talk with injured cells is required for renal
      regeneration supported by bone marrow-derived cells.

PMID- 21865735
TI  - Carnosine prevents apoptosis of glomerular cells and podocyte loss in STZ
      diabetic rats.
AB  - BACKGROUND/AIMS: We identified carnosinase-1 (CN-1) as risk-factor for diabetic
      nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective
      factor regarding diabetic complications. In this study, we hypothesized that
      carnosine administration to diabetic rats might protect the kidneys from
      glomerular apoptosis and podocyte loss. METHODS: We examined the effect of oral L
      carnosine administration (1g/kg BW per day) on apoptosis, podocyte loss,
      oxidative stress, AGEs and hexosamine pathway in kidneys of streptozotocin
      induced diabetic Wistar rats after 3 months of diabetes and treatment. RESULTS:
      Hyperglycemia significantly reduced endogenous kidney carnosine levels. In
      parallel, podocyte numbers significantly decreased (-21% compared to non
      diabetics, p<0.05), apoptotic glomerular cells numbers increased (32%, compared
      to non-diabetic, p<0.05) and protein levels of bax and cytochrome c increased
      (175% and 117%). Carnosine treatment restored carnosine kidney levels, prevented
      podocytes loss (+23% compared to diabetic, p<0.05), restrained glomerular
      apoptosis (-34% compared to diabetic; p<0.05) and reduced expression of bax and
      cytochrome c (-63% and -54% compared to diabetics, both p<0.05). In kidneys of
      all diabetic animals, levels of ROS, AGEs and GlcNAc-modified proteins were
      increased. CONCLUSION: By inhibition of pro-apoptotic signaling and independent
      of biochemical abnormalities, carnosine protects diabetic rat kidneys from
      apoptosis and podocyte loss.

PMID- 21865736
TI  - Paracellular permeability of bronchial epithelium is controlled by CFTR.
AB  - In normal airway epithelium, the cystic fibrosis transmembrane conductance
      regulator (CFTR) transports Cl(-) ions to the apical surface of the epithelium
      paralleled by the flow of water through transcellular and paracellular pathways.
      The hypothesis was tested whether CFTR not only regulates the transcellular but
      also the paracellular shunt pathway. Therefore, we performed measurements of
      transepithelial electrical resistance (TER) and paracellular (14)C-mannitol
      permeability in wtCFTR (16HBE14o(-)) and delF508-CFTR (CFBE41o(-)) expressing
      human bronchial epithelial cells. Under resting conditions, CFBE41o(-) cell
      monolayers exhibit a higher paracellular permeability and lower TER as compared
      to 16HBE14o(-) monolayers. Stimulation of CFTR by cAMP induces opposite effects
      in the two cell lines. 16HBE14o(-) monolayers show a sharp decrease of TER, in
      parallel with a concomitant increase of paracellular permeability. The change in
      paracellular permeability is mediated by a myosin II dependent mechanism because
      it can be blocked by the myosin light chain kinase inhibitor ML-7. In contrast,
      CFBE41o(-) cells respond to cAMP stimulation with a decrease of paracellular
      permeability, paralleled by slight increase of TER. We conclude that stimulation
      of wtCFTR increases vectorial transcellular salt transport and, simultaneously,
      the paracellular permeability allowing water to follow through the paracellular
      pathway. In contrast, in CF epithelium cAMP stimulation increases neither
      vectorial salt transport nor paracellular permeability which is likely to
      contribute to the CF pulmonary phenotype. Taken together, our results link CFTR
      dysfunction to an improper regulation of the paracellular transport route.

PMID- 21865737
TI  - Stretch-inducible expression of connective tissue growth factor (CTGF) in human
      osteoblasts-like cells is mediated by PI3K-JNK pathway.
AB  - To explore the possible role for connective tissue growth factor (CTGF) during
      tooth movement, we evaluated CTGF gene and protein expression in MG-63 cells
      subjected to cyclic stretch. Cyclic stretch caused a time-dependent increase in
      CTGF mRNA and protein levels.Inhibition of p38 MAP kinase or ERK activation did
      not affect cyclic stretch-induced CTGF expression. Specific inhibitors of PI3K
      suppressed stretch -induced CTGF expression in a time-dependent manner. cyclic
      stretch activated JNK and ERK, but not p38 MAP kinase in osteoblast-like cells.
      PI3K inhibitors suppressed cyclic stretch-induced JNK, but not p38 MAP kinase
      activation. Finally, SP600125, a Specific Inhibitor of JNK, suppressed stretch 
      induced CTGF Expression. These results suggest that stretch-induced CTGF
      expression is mediated through the PI3K-JNK -dependent pathway, not by p38 MAP
      kinase and ERK pathways.

PMID- 21865738
TI  - Influence of dexamethasone on na+/h+ exchanger activity in dendritic cells.
AB  - Glucocorticoids regulate the function of dendritic cells (DCs), antigen
      presenting cells linking innate and adaptive immunity. Glucocorticoids influence
      the function of other cell types by modulating the activity of the
      Na(+)/H(+)exchanger (NHE), a carrier involved in the regulation of cytosolic pH
      and cell volume. The present study explored whether dexamethasone influences
      Na(+)/H(+) exchanger activity in DCs. The DCs were isolated from mouse bone
      marrow, cell volume was estimated from forward scatter in FACS analysis,
      cytosolic pH (pH(i)) utilizing BCECF fluorescence and Na(+)/H(+) exchanger
      activity from the Na(+) dependent realkalinization after an ammonium pulse.
      Treatment with the glucocorticoid dexamethasone (100 nM; 1, 4, 16 and 24h)
      significantly decreased pH(i) (>=4 h) and gradually increased Na(+)/H(+)
      exchanger activity (=16 h). The stimulation of Na(+)/H(+) exchanger activity by
      dexamethasone was virtually abrogated by glucocorticoid receptor blocker
      mefiprestone (1 MUM) and NHE3 inhibitor dimethyl amiloride (5 MUM), but not
      prevented by NHE1 inhibitor cariporide (10 MUM). Dexamethasone treatment
      significantly increased SGK1 mRNA levels. Stimulation of Na(+)/H(+) exchanger
      activity by dexamethasone was blunted in DCs lacking SGK1. Dexamethasone
      treatment did not significantly alter ROS formation but significantly decreased
      the forward scatter. Exposure of DCs to lipopolysacharide (LPS, 1 MUg/ml) led to
      a transient increase followed by a decline of Na(+)/H(+) exchanger activity and
      to enhanced forward scatter as well as ROS formation, all effects significantly
      blunted in the presence of dexamethasone (100 nM). In conclusion, glucocorticoid
      treatment decreased pH(i) and cell volume, effects paralleled by upregulation of
      Na(+)/H(+) exchanger activity in DCs. Moreover, glucocorticoids blunted the
      stimulation of Na(+)/H(+) exchanger activity, cell swelling and ROS formation
      following LPS treatment.

PMID- 21865739
TI  - Chronic beta-adrenoceptor antagonists upregulate the rat alveolar macrophage
      adrenergic system through the beta1-subtype.
AB  - BACKGROUND: Previous studies demonstrate that macrophages synthesis and release
      catecholamines, which regulate the immune responses in an autocrine manner. These
      responses are mediated in part by beta-adrenoceptors expressed on macrophages.
      Some beta-adrenoceptor antagonists are commonly used in clinical conditions. Here
      we investigated whether the chronic administration of beta-adrenoceptor
      antagonists upregulate adrenergic system of alveolar macrophage and the potential
      mechanims. METHODS: Propranolol (30 mg/kg.d) or atenolol (5 mg/kg.d) was
      administered by gavage to rats for 4 weeks. Then alveolar macrophages were
      isolated and the expression of beta(1) or beta(2)-adrenoceptor was detected by
      flow cytometric analysis. Dopamine beta-hydroxylase expression was assessed by
      Western blot assay and the concentrations of noradrenaline, IL-6, and TNF-alpha
      in cell supernatants were measured using ELISA after 2 h or 24 h exposure of
      alveolar macrophages to 100 ng/ml lipopolysaccharide (LPS). RESULTS: Propranolol
      increased the mean fluorescence intensity (MFI) of beta(1), beta(2)-adrenoceptor
      and the frequency of beta(1)-,beta(2)- adrenoceptor positive macrophages.
      However, only the MFI of beta(1)-adrenoceptor and the frequency of beta(1)
      adrenoceptor positive macrophages were increased by atenolol. Furthermore, both
      propranolol and atenolol promoted LPS-mediated dopamine beta-hydroxylase protein
      expression and increased noradrenaline production in rat alveolar macrophages.
      This was accompanied by increased LPS-mediated IL-6 and TNF-alpha production in
      cell supernatants of alveolar macrophages. CONCLUSION: These findings demonstrate
      that propranolol or atenolol upregulates alveolar macrophage adrenergic system,
      and the response may be beta(1)-adrenergic receptor subtype dependent.

PMID- 21865740
TI  - Mononuclear derived from human umbilical cord normalize glycemia in alloxan
      induced hyperglycemic rat.
AB  - The present study explored whether mononuclear cells derived from human umbilical
      cord blood could resolve hyperglycemia. In order to test this hypothesis,
      mononuclear cells derived from Human umbilical cord blood (HUCB) were
      transplanted into alloxan-induced hyperglycemic rats. Mononuclear cells (MNCs)
      were isolated by a conventional centrifuge method through a Ficoll- paque.
      Hyperglycemia was induced in rats by a single injection of alloxan at 50 mg/kg
      body weigh intraperitonealy. Rats were divided into three groups of ten each.
      Group I, served as control; Group II received alloxan alone; Group III received
      both alloxan and MNCs. The serum glucose and insulin level were measured before
      the animals received the MNCs and at 1, 4, 7, 12 and 15 weeks following the
      treatment. Glucose levels were monitored by the glucose oxidase technique. The
      insulin level was measured following Elisa assay by the insulin kit specific for
      rats made by Mercodia Co., Sweden. The results indicated that glucose levels in
      alloxan-injected rats rose at week 1 and remained elevated 301.00 +/- 6.43 mg/dl
      for 15 weeks. In contrast, in week 15, after treated with MNCs, the blood glucose
      levels were 108.26 +/- 6.84, mg/dl. Within a week after MNCs administration,
      blood glucose levels significantly reduced (245.74 +/- 2.37 mg/dl and reached a
      baseline almost close to the normal glycemic values 15 week later (108.26 +/-
      6.84 mg/dl). Treated with MNCs in alloxan diabetic rats caused a significant rise
      in serum insulin accompanied by a drop in the blood glucose level.

PMID- 21865741
TI  - Activation of human neutrophils by oleic acid involves the production of reactive
      oxygen species and a rise in cytosolic calcium concentration: a comparison with N
      6 polyunsaturated fatty acids.
AB  - BACKGROUND: There is a growing body of evidence showing that dietary constituents
      and lipids in particular, influence the function of the human immune system.
      However, although the beneficial effects of oleic acid (OA) are clear, its
      mechanism of action at the molecular level is poorly understood. AIMS: To
      evaluate neutrophil activation under the influence of OA and compare this with
      several n-6 PUFAs. METHODS: Two key aspects of neutrophil activation were
      investigated: oxygen radical (ROS) production and intracellular Ca(2+) signaling.
      RESULTS: OA and the n-6 PUFA arachidonic acid (AA) both induced ROS production in
      a dose-dependent manner, although AA was the more potent stimulus. When looking
      for the mechanisms behind these effects, we found that both FA induce increases
      in cytosolic calcium concentration [Ca(2+)](i)), but whereas OA-induced ROS
      production is totally mediated through Ca2+ signaling, this is not the case for
      AA since ROS generation by AA is only partly inhibited in BAPTA-treated cells. We
      also found evidence for the involvement of protein kinase C (PKC) in the OA
      induced ROS generation; by contrast, other enzymes apart from PKC seem to be
      implicated in n-6 PUFA-induced ROS production. In addition, our results argue
      against the involvement of a pertussis toxin-sensitive receptor activated by OA.
      CONCLUSIONS: OA differs from the n-6 PUFA AA in the activation of human
      neutrophils and these differences may be related to their distinct
      inmunomodulatory properties.

PMID- 21865742
TI  - Sphingosine but not sphingosine-1-phosphate stimulates suicidal erythrocyte
      death.
AB  - Sphingosine kinase 1 phosphorylates sphingosine, which is converted to ceramide
      by ceramide synthetase. Ceramide triggers eryptosis, the suicidal erythrocyte
      death characterized by cell shrinkage and phosphatidylserine (PS) exposure at the
      erythrocyte surface. Erythrocytes lack sphingosine phosphate-degrading enzymes
      and thus store large quantities of sphingosine phosphate. The present study
      explored the influence of sphingosine and sphingosine phosphate on eryptosis.
      [Ca(2+)](i), was estimated from Fluo3 fluorescence, cell volume from forward
      scatter and PS exposure from annexin V-binding in FACS analysis. Sphingosine (0.1
      - 10 MUM) but not sphingosine-1- phosphate (0.1 - 10 MUM) increased [Ca(2+)](i),
      decreased cell volume and increased PS-exposure. The observations disclose
      sphingosine, but not sphingosine-1-phosphate, as a strong inducer of eryptosis.

PMID- 21865743
TI  - Stimulation of suicidal erythrocyte death by benzethonium.
AB  - Benzethonium, an antimicrobial surfactant widely used as preservative of
      pharmaceuticals, topical wound care product and oral disinfectant, triggers
      apoptosis of several cell types. The apoptosis is preceded and possibly triggered
      by mitochondrial depolarization. Even though lacking mitochondria, erythrocytes
      may similarly undergo suicidal cell death or eryptosis. Hallmarks of eryptosis
      include cell shrinkage and cell membrane scrambling with phosphatidylserine
      exposure at the cell surface. Eryptosis may be triggered by energy depletion,
      which leads to increase of cytosolic Ca(2+)-activity with subsequent Ca(2+)
      sensitive cell shrinkage and cell membrane scrambling. Ca(2+)-sensitivity is
      enhanced by ceramide. The present study explored the effect of benzethonium on
      eryptosis. Cell membrane scrambling was estimated from binding of fluorescent
      annexin V to phosphatidylserine, cell volume from forward scatter in FACS
      analysis, cytosolic Ca(2+)-concentration from Fluo3-fluorescence, hemolysis from
      hemoglobin release, lactate formation by colorimetry and ceramide utilizing
      fluorescent antibodies. A 48 hours exposure to benzethonium (=5MUM) significantly
      increased cytosolic Ca(2+)-concentration, decreased forward scatter and triggered
      annexin V-binding affecting some 30% of the erythrocytes at 5 MUM benzethonium.
      Only 5% of treated erythrocytes were hemolytic. The effects of benzethonium on
      annexin V binding were blunted in the nominal absence of Ca(2+) and in the
      presence of amiloride (1 mM) but not in the presence of the pancaspase inhibitor
      zVAD (10 MUM). Benzethonium further significantly enhanced the effect of glucose
      depletion on cytosolic Ca(2+)-concentration and annexin V-binding, but
      significantly blunted the effect of glucose depletion on forward scatter.
      Benzethonium (5 MUM) significantly enhanced lactic acid formation but not
      ceramide abundance. The present observations disclose a novel effect of
      benzethonium, i.e. triggering of suicidal death of erythrocytes.

PMID- 21865744
TI  - Involvement of P2X receptors in the regulation of insulin secretion,
      proliferation and survival in mouse pancreatic beta-cells.
AB  - In order to clarify the functional role of ionotropic purinergic (P2X) receptors
      in pancreatic beta-cells, we examined the effect of several P2 receptor agonists
      and antagonists on insulin secretion by mouse pancreatic islets, mouse Beta-TC6
      cell proliferation and survival of dispersed islet cells in culture. Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis showed the expression
      of mRNAs of P2X(4) receptor in mouse islets and P2X(1), P2X(2), P2X(3), P2X(4),
      P2X(5) and P2X(7) receptors in Beta-TC6 cells. The presence of P2X(4) receptor
      proteins in islets and Beta-TC6 cells was confirmed by immunofluorescent staining
      and Western blot analysis. We have previously found that the functional P2Y(1)
      receptor but not P2Y(2) and P2Y(4) receptors was present in islets. In this study
      we found that a nonspecific P2 receptor agonist, ATP (1 MUM) stimulated insulin
      secretion by islets in the presence of high glucose (20 mM) in culture. The
      effect of ATP was partially inhibited by a P2 receptor antagonist PPADS as well
      as a P2Y(1) receptor antagonist MRS2179. In addition, a P2X(4) receptor
      potentiator ivermectin per se augmented glucose-induced insulin secretion and
      slightly potentiated the effect of ATP. These results suggested the involvement
      of P2Y(1)and P2X receptors. We also found that ATP inhibited proliferation of
      Beta-TC6 cells in a concentration-dependent manner during 72 h culture. The
      inhibitory effect of ATP was completely reversed by PPADS and partially by
      treating cells with small interfering RNA targeted for P2X(4) receptor mRNA.
      Furthermore, we found that the phosphorylation of the extracellular signal
      regulated kinase 1 and 2 (ERK1/2) was suppressed by treatment with ATP in Beta
      TC6 cells. In addition, we found that ATP reduced the cell viability and DNA
      synthesis of islet cells in culture. The effect of ATP on the cell viability was
      blocked by PPADS or MRS2179. These results suggested that P2X receptors as well
      as the P2Y(1) receptor played a role in the modulation of insulin secretion,
      proliferation and cell viability in mouse pancreatic beta-cells.

PMID- 21865745
TI  - Panax notoginseng saponins promote osteogenic differentiation of bone marrow
      stromal cells through the ERK and P38 MAPK signaling pathways.
AB  - The Chinese medicinal herb, Panax notoginseng, has long been used to treat bone
      fractures and Panax notoginseng saponins (PNS) could promote bone formation.
      Here, we investigated whether PNS could promote osteogenesis of bone marrow
      stromal cells (BMSCs) through modulating the MAPK signaling pathways, which are
      implicated in BMSC osteogenesis. We found that PNS markedly increased the
      mineralization of BMSCs by alizarin red S assays and stimulate alkaline
      phosphatase activity of these cells. Additionally, PNS significantly increased
      the mRNA levels of alkaline phosphatase, core-binding factor a1, and bone
      sialoprotein while decreasing PPARgamma2 mRNA levels. Furthermore, inhibitors of
      ERK, PD98059, and p38, SB203580 inhibited the osteogenesis-potentiating effects
      by PNS. PNS stimulated the activation of ERK and p38 as evidenced by increased
      phosphorylation of these proteins, which was inhibited by PD98059 and SB203580.
      Our findings indicate that PNS could promote BMSC osteogenesis by activating the
      ERK and p38 signaling pathways.

PMID- 21865746
TI  - A blood-based algorithm for the detection of Alzheimer's disease.
AB  - BACKGROUND: We previously created a serum-based algorithm that yielded excellent
      diagnostic accuracy in Alzheimer's disease. The current project was designed to
      refine that algorithm by reducing the number of serum proteins and by including
      clinical labs. The link between the biomarker risk score and neuropsychological
      performance was also examined. METHODS: Serum-protein multiplex biomarker data
      from 197 patients diagnosed with Alzheimer's disease and 203 cognitively normal
      controls from the Texas Alzheimer's Research Consortium were analyzed. The 30
      markers identified as the most important from our initial analyses and clinical
      labs were utilized to create the algorithm. RESULTS: The 30-protein risk score
      yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91,
      respectively. When combined with demographic data and clinical labs, the
      algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94,
      respectively. In linear regression models, the biomarker risk score was most
      strongly related to neuropsychological tests of language and memory. CONCLUSIONS:
      Our previously published diagnostic algorithm can be restricted to only 30 serum
      proteins and still retain excellent diagnostic accuracy. Additionally, the
      revised biomarker risk score is significantly related to neuropsychological test
      performance.

PMID- 21865747
TI  - Influence of variation in the follicle-stimulating hormone receptor gene (FSHR)
      and age at menopause on the development of Alzheimer's disease in women.
AB  - BACKGROUND: The higher prevalence of sporadic Alzheimer's disease (AD) in women
      may be explained by their longer life expectancy, but also by biological gender
      specific factors such as a woman's past fertility. METHODS: We investigated the
      relationship between fertility and susceptibility to AD in women by studying two
      polymorphisms at codons 307 and 680 of the follicle-stimulating hormone receptor
      gene (FSHR) involved in determining human fertility. The role of age at menopause
      (AM) as a gender-specific AD susceptibility determinant was also examined. The
      study population comprised 291 AD patients (70.1% women) and 134 controls (63.4%
      women). RESULTS: Logistic regression analysis showed that only among the women
      the FSHR AS/AS genotype was associated with a significantly lower risk of AD (OR
      = 0.36, 95% CI: 0.15-0.85), suggesting a gender-specific protective role of the
      FSHR genotype against AD susceptibility. A lower age at natural menopause was
      observed in the AD patients (49.7 +/- 2.53) than in the controls (50.7 +/- 2.53,
      p = 0.02) and on linear regression analysis an association emerged between an
      earlier AM and an earlier AD onset (p = 0.004). CONCLUSIONS: Genetic and non
      genetic gender-specific factors may contribute to the AD pathogenesis in women,
      although further investigations are required to clarify their actual role.

PMID- 21865748
TI  - 'Red alert' or not? - do we give our inflammatory bowel disease patients the
      right dietary recommendations?

PMID- 21865749
TI  - Chondrocyte proliferation and differentiation.
AB  - The skeletal elements of the axial and appendicular skeleton are preformed as
      cartilage templates by a mechanism called endochondral ossification. During this
      process, a cartilage template is formed in which chondrocytes proliferate and
      differentiate into hypertrophic chondrocytes and are gradually replaced by bone.
      Postnatally, remnants of embryonic chondrocytes remain in a restricted domain
      between the ossified regions of the bones forming the growth plate. The
      coordinated proliferation and differentiation of chondrocytes ensures the
      continuous elongation of the epiphyseal growth plates. The sequential changes
      between proliferation and differentiation are tightly regulated by secreted
      growth factors, which activate chondrocyte-specific transcription factors.
      Transcription factors that play critical roles in regulating cell type-specific
      gene expression include SOX9, GLI2/3 and RUNX2. This review will outline recent
      advances in the analysis of the complex transcriptional network that regulates
      distinct steps of chondrocyte differentiation.

PMID- 21865750
TI  - Local regulation of growth plate cartilage.
AB  - Elongation of bones primarily occurs by endochondral ossification at the growth
      plate. In the growth plate, stem-like cells in the resting zone differentiate
      into rapidly dividing chondrocytes in the proliferative zone and then terminally
      differentiate into nondividing chondrocytes of the hypertrophic zone. The
      hypertrophic zone is then invaded by blood vessels and bone cell precursors,
      which remodel the newly formed cartilage into bone. The net effect is that new
      bone tissue is progressively generated at the bottom of the growth plate,
      resulting in bone elongation. The process of longitudinal bone growth is governed
      by a complex network of paracrine signals that maintain the unique structure and
      cellular kinetics of the growth plate. Recent progress in the understanding of
      important paracrine signals that regulate growth plate cartilage will be reviewed
      in this chapter.

PMID- 21865751
TI  - Growth plate senescence and catch-up growth.
AB  - Longitudinal bone growth is rapid in prenatal and early postnatal life, but then
      slows with age and eventually ceases. This growth deceleration is caused
      primarily by a decrease in chondrocyte proliferation, and is associated with
      other structural, functional, and molecular changes collectively termed growth
      plate senescence. Current evidence suggests that growth plate senescence occurs
      because the progenitor chondrocytes in the resting zone have a limited
      replicative capacity which is gradually exhausted with increasing cell division.
      In addition, recent experimental findings from laboratory and clinical studies
      suggest that growth plate senescence explains the phenomenon of catch-up growth.
      Growth-inhibiting conditions such as glucocorticoid excess and hypothyroidism
      delay the program of growth plate senescence. Consequently, growth plates are
      less senescent after these conditions resolve and therefore grow more rapidly
      than is normal for age, resulting in catch-up growth.

PMID- 21865752
TI  - Endocrine regulation of longitudinal bone growth.
AB  - Longitudinal growth is primarily influenced by the GH-IGF-I axis, which is a
      mixed endocrine-paracrine-autocrine system. Further, classical hormones such as
      thyroxine, glucocorticosteroids and sex steroids play a role, as well as
      primarily paracrine systems. In the GH-IGF-I axis, seven disorders can be
      differentiated: (1) GH deficiency; (2) GHR defects; (3) defects in the GH signal
      transduction pathway; (4) IGF1 defects; (5) IGFALS defects; (6) IGF1R defects,
      and (7) IGF2 defects. Children with one of the first 3 disorders have near-normal
      prenatal growth, while children with defects of IGF1, IGF1R or IGF2 show prenatal
      as well as postnatal growth retardation. Hypothyroidism or a thyroid hormone
      resistance cause growth failure, but the effect of hyperthyroidism on growth is
      modest. Hypercortisolism causes poor growth, while FGD caused by ACTH
      insensitivity is associated with tall stature. Increased sex steroids in
      childhood cause advanced growth but even more skeletal maturation, so that adult
      height is decreased. Finally, the paracrine-autocrine SHOX-BNP pathway and the
      related CNP-NPR2 pathway are also involved in growth, as very many other growth
      factors and their receptors and mediators.

PMID- 21865753
TI  - Estrogen signaling in growth plate cartilage.
AB  - It is well known that sex steroids, in particular estrogens, play an important
      role in longitudinal bone growth during puberty. High doses of estrogen therapy
      can reduce the final height of an individual, but such treatment is also
      associated with severe side effects. At the same time, attenuation of estrogen
      production by aromatase inhibitors increases adult final height, inhibiting bone
      turnover, which influences bone architecture and may increase the risk for
      vertebrae fractures. SERMs, which display either estrogenic and/or antiestrogenic
      effects, bind to ERs with different affinities and subsequently recruit co
      modulators of transcription in a tissue-specific manner.

PMID- 21865754
TI  - Methods to study cartilage and bone development.
AB  - In humans, the study of linear growth at the level of growth plate is limited to
      the use of mainly noninvasive methods. The use of in vitro studies and diverse
      animal models are alternative applied methods to unravel the underlying
      mechanisms of endochondral ossification and bone remodeling. In this chapter, we
      will outline important techniques to study molecular interactions and the
      regulation of gene expression in chondrocytes as well as bone cells.
      Microdissection of growth plate provides a powerful approach to study gene
      expression of individual zones and temporal senescence of growth plate cartilage
      by using microarray and real-time PCR analysis. IHC gives valuable information
      about the distribution of proteins of interest throughout distinct layers of the
      growth plate. The TUNEL assay has been successfully applied to study apoptosis in
      chondrocytes. In addition, organ(metatarsal) culture, primary and cell line
      cultures have been widely used to explore the regulation of chondrocyte
      differentiation under varying experimental conditions. Ultimately, these methods
      are essential to give new insights into the search for new diagnostic and
      therapeutic approaches for growth and various metabolic bone disorders.

PMID- 21865755
TI  - Fibroblast growth factor-23 and phosphorus metabolism.
AB  - The understanding of phosphorus metabolism has expanded considerably over the
      last decade. Recent studies have identified a novel bone-kidney endocrine axis
      that maintains phosphate homeostasis. When phosphate is in excess, FGF-23 is
      secreted from bone and acts on the kidney to promote phosphate excretion into
      urine and to suppress vitamin D synthesis, thereby inducing negative phosphate
      balance. This review summarizes the role of the FGF-23 axis on phosphorus
      metabolism, and presents the clinical entities that arise from activation or
      inactivation of the FGF-23 axis.

PMID- 21865756
TI  - Molecular defects causing skeletal dysplasias.
AB  - Almost 400 different forms of skeletal dysplasias have been described, each with
      characteristic clinical and radiographic features. The underlying genetic and
      molecular pathology is known in several forms. Correct diagnosis is important for
      genetic counseling, treatment decisions, follow-up and for predicting long-term
      outcome. With advances in molecular genetics it has become evident that variable
      phenotypes can be caused by mutations in one gene, depending on the mutation type
      and location within the gene. On the other hand, mutations in different genes can
      result in similar phenotypes. Careful clinical assessment with thorough
      radiographic evaluation are of key importance.

PMID- 21865757
TI  - Allele-specific gene silencing in osteogenesis imperfecta.
AB  - OI is caused by mutations in the genes encoding for collagen type I COL1A1 and
      COL1A2, respectively. The patients suffer from bone fragility, and the severity
      can range from mild, with fractures in the youth, to lethal forms. Today, there
      is no effective treatment for the disorder. OI is caused by dominant negative
      mutations. A tempting approach to treat the disease would be to silence the
      allele carrying the mutation. This could in theory be done with siRNAs. Today,
      more than 800 various mutations are reported, and to create siRNA against a
      specific mutation is difficult. Instead, by developing siRNA against common
      polymorphic variations, it would be possible to silence the mutation by a
      standardized method regardless where the mutation is located on the allele. If
      the concept of allele-specific gene silencing by inhibitory RNA directed towards
      dominant negative mutations could be proven, this might be a novel approach to
      gene therapy in OI.

PMID- 21865758
TI  - Stem cells in skeletal physiology and endocrine diseases of bone.
AB  - Self-renewing, multipotent progenitors of skeletal tissues are found within
      skeletal segments (skeletal stem cells) and coincide with adventitial reticular
      cells of bone marrow vessels in situ and with explanted clonogenic stromal cells
      ex vivo. These cells, which can be identified and prospectively isolated based on
      a minimal surface phenotype noted for expression of CD146, CD105 and alkaline
      phosphatase, are established during bone development through interactions with
      developing sinusoids. They represent a crucial crossroad of skeletal and
      hematopoietic physiology, as well as of endocrine regulation of bone growth and
      remodeling. In addition, they are central to major endocrine functions of bone
      itself, such as regulation of renal phosphate handling. Skeletal stem cells
      represent a central model system for investigating skeletal diseases, as tools
      for in vitro and in vivo models, for cell therapy-based strategies, or as targets
      for drugs.

PMID- 21865759
TI  - Cartilage tissue engineering.
AB  - Cartilage tissue engineering is the art aimed at repairing defects in the
      articular cartilage which covers the bony ends in the joints. Since its
      introduction in the early 1990s of the past century, cartilage tissue engineering
      using ACI has been used in thousands of patients to repair articular cartilage
      defects. This review focuses on emerging strategies to improve cartilage repair
      by incorporating fundamental knowledge of developmental and cell biology in the
      design of optimized strategies for cell delivery at the defect site and to
      locally stimulate cartilage repair responses.

PMID- 21865760
TI  - Reduced serum caeruloplasmin levels in non-wilsonian movement disorders.
AB  - Reduction in caeruloplasmin (Cp) levels is sometimes found in other sporadic
      movement disorders, not limited to Wilson's disease (WD). Serum levels of Cp,
      copper, iron and gamma-glutamyl transpeptidase were measured in 71 patients with
      various diagnoses of movement disorders, including Parkinson's disease (PD),
      atypical parkinsonian disorders, tardive dyskinesia, essential tremor, and
      idiopathic focal dystonia, and compared with those of 26 healthy age- and gender
      matched controls. The mean Cp level in the patient group was 20.5 +/- 4.2 mg/dl ,
      lower than in controls (23.5 +/- 7.2 mg/dl; p = 0.005). In subgroup analysis,
      mean Cp level of PD patients (19.6 +/- 3.0 mg/dl) was lower than that of controls
      (p = 0.045). In a group analysis as neurodegenerative movement disorders (NDD),
      their mean Cp level was 19.9 +/- 3.0 mg/dl, lower than that of controls (p =
      0.019). Linear regression analysis indicated that the presence of NDD was the
      main factor associated with lower Cp levels. The finding of reduced serum Cp
      level in non-Wilsonian movement disorders and selective reduction in the
      neurodegenerative subgroup supports the notion that Cp might be associated with
      the cascade of neurotoxicity in NDD. The variation in Cp level in other non-WD
      conditions highlights the fact that Cp level is a poor screening test for WD in
      the absence of clear clinical suspicion.

PMID- 21865761
TI  - The use of S100B and Tau protein concentrations in the cerebrospinal fluid for
      the differential diagnosis of bacterial meningitis: a retrospective analysis.
AB  - BACKGROUND: Patients with meningitis are often difficult to classify into
      bacterial (BM) or benign viral (VM) meningitis. To facilitate the differential
      diagnosis, S100B and Tau protein in the cerebrospinal fluid (CSF) were measured
      and compared with standard laboratory parameters. METHODS: S100B(CSF), Tau(CSF),
      and routine parameters (CSF leukocyte count, protein(CSF), lactate(CSF), serum C
      reactive protein, blood leukocyte count and body temperature) were analyzed in 33
      patients with microbiologically confirmed BM and in 19 with VM. Their
      classification accuracy, sensitivity and specificity were studied by receiver
      operating characteristic (ROC) curves. RESULTS: S100B(CSF) concentrations were
      higher in BM than in VM patients (p = 0.03) and showed a promising accuracy (90%)
      for the differential diagnosis of BM versus VM. Its discriminative properties
      were comparable to routine parameters. Of all parameters, S100B(CSF) showed the
      highest specificity (100%) with an optimal cut-off of 3.1 ng/ml. Tau(CSF)
      concentrations were useless for the discrimination (p = 0.64). CONCLUSIONS: In
      contrast to Tau(CSF), S100B(CSF) concentrations >=3.1 ng/ml are promising to
      discriminate bacterial from viral meningitis.

PMID- 21865762
TI  - Ischemic stroke presenting as thunderclap headache: report of two cases and
      review of the literature.

PMID- 21865763
TI  - Associations between Circle of Willis morphology and white matter lesion load in
      subjects with carotid artery stenosis.
AB  - BACKGROUND: Various cerebral pathological changes have been reported to cause
      leukoaraiosis (LA). We hypothesized that circle of Willis (CoW) anomalies may
      contribute to LA in severe carotid artery stenosis victims through impaired
      cerebral autoregulation. We conducted a retrospective review on cerebral magnetic
      resonance (MR) patterns in patients with severe symptomatic carotid artery
      stenosis and compared white matter lesion (WML) load between subjects with and
      without complete CoW. METHODS: LA on fluid attenuation inversion recovery (FLAIR)
      MR images at the levels of the centrum semiovale and frontal horns in both
      cerebral hemispheres were scored in 106 patients with unilateral carotid artery
      stenosis (64 men and 42 women; mean age 68.7 +/- 9.2 years, range 44-82).
      Subjects were divided into groups of complete and incomplete CoW according to
      cerebral MR angiography. Differences in the LA scores between the groups of
      complete and incomplete CoW were further analyzed. RESULTS: Compared with those
      with incomplete configuration of the CoW, subjects with a complete CoW
      demonstrated a decreased WML load at the level of the centrum semiovale (2.78 +/-
      1.17 vs. 5.62 +/- 2.12, p = 0.02) and frontal horns (2.21 +/- 0.79 vs. 4.22 +/-
      1.83, p = 0.01). CONCLUSION: Our results support the importance of a complete CoW
      since it may protect from WML in case of carotid stenosis.

PMID- 21865764
TI  - Decolorizing activity of malachite green and its mechanisms involved in dye
      biodegradation by Achromobacter xylosoxidans MG1.
AB  - An Achromobacter xylosoxidans MG1 strainisolated from the effluent treatment
      plant of a textile and dyeing factory from Yunnan Province in China was found
      capable of decolorizing the malachite green dye at a high efficacy. Strain MG1
      reduced 86% malachite green at the concentration of 2,000 mg/l within 1 h,
      representing a greater ability for decolorizing and a higher tolerance of this
      compound than all previously reported bacteria. Color removal was optimal at pH 6
      and 38 degrees C. Further experimental evidences demonstrated that both
      cytoplasmic and extracellular biodegradation contributed to the decolorization of
      malachite green. Nested PCR was employed to identify the candidate genes
      responsible for malachite green decolorization, and we identified a cytoplasmic
      triphenylmethane reductase gene with 100% amino acid similarity to the
      corresponding gene in Citrobacter sp. strain. In contrast to our expectation, the
      addition of metyrapone had little effect on the cytoplasmic biodegradation,
      suggesting that cytochrome P450 was not involved in the high-performance
      reduction. The extracellular biodegradation was likely attributable to the
      secretion of extracellular proteases and some heat-resistant compounds.

PMID- 21865765
TI  - Excessive milk intake as a risk factor, probably associated with oxidative
      stress, in experimental naphthalene-initiated cataract in rats.
AB  - AIM: To determine whether a diet containing excessive amounts of milk aggravates
      naphthalene-initiated cataracts in a common animal model of age-related human
      cataract. METHODS: Ninety Sprague-Dawley rats were fed a natural diet
      supplemented with either water (group A), normal amounts of milk (group B),
      excessive amounts of milk (group C), naphthalene plus water (group D),
      naphthalene plus normal amounts of milk (group E), naphthalene plus excessive
      amounts of milk (group F). Cataract development was monitored weekly using a slit
      lamp and lens gray value analysis. Concentrations of reactive oxygen species
      (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) in rat lenses were
      measured to determine the role of oxidative stress in cataract induction.
      RESULTS: By week 4, the cortical gray value was significantly higher in group F
      than that in group D, and the cortical gray value was significantly higher in
      group D than in group A. However, by week 8, no significant differences were
      observed among groups C, F, B, E and A. ROS concentrations in lenses of rats of
      groups C and F were slightly higher than in those of groups B, E and A, but ROS
      concentrations in group F were significantly higher than in the other groups
      receiving naphthalene (i.e. groups D and E). GSH concentrations in group F were
      significantly lower than in the other groups. MDA concentrations in group F were
      significantly higher than in the other groups receiving naphthalene, indicating
      increased lipid peroxidation induced by naphthalene plus excessive intake of
      milk. CONCLUSIONS: Our results provide quantitative evidence that excessive
      intake of milk aggravates naphthalene-initiated cataracts, which is probably due
      to oxidative damage caused by increased ROS.

PMID- 21865766
TI  - Bacteriologic evaluation of sinus aspirates taken by balloon catheter devices in
      chronic rhinosinusitis: preliminary study.
AB  - PURPOSE: Chronic rhinosinusitis (CRS) is known to be a polymicrobial infection
      involving both aerobes and Gram-positive and Gram-negative anaerobes. Accurate
      bacterial evaluation by adequate culture methods can justify subsequent
      antimicrobial strategies. METHODS: Two specimens were obtained from each of 10
      patients undergoing catheter-based Balloon SinuplastyTM, one from the middle
      meatus (endoscopic approach) and the other from the sinus (catheter-based
      approach). RESULTS: The bacterial culture from the middle meatus was positive in
      9 of 10 patients, including 6 different aerobes without anaerobes. The bacterial
      culture of aspirates from the sinuses were positive in 8 out of 10 patients, with
      4 different aerobic bacteria and 4 different anaerobic bacteria. Anaerobes were
      isolated in 0% of middle meatus samples, which was significantly lower than the
      62.5% (5/8) detected in the sinus samples. CONCLUSIONS: Bacterial culture of
      sinus aspirates using a catheter-based technique improves the recovery of
      bacterial pathogens from CRS patients.

PMID- 21865767
TI  - Anti-inflammatory and immunomodulatory effects of bortezomib in various in vivo
      models.
AB  - Bortezomib (Velcade(r)) is a proteasome inhibitor that has been approved for the
      treatment of multiple myeloma and mantle cell lymphoma. It has been shown to
      inhibit the expression of cell adhesion molecules, co-stimulatory molecules, and
      NFkappaB activation, to deplete alloreactive T lymphocytes, and to decrease Th1
      cytokine production. The anti-inflammatory effects of bortezomib were further
      investigated in this current set of studies. Systemic treatment with bortezomib
      was efficacious in the thioglycolate-induced MCP-1 production model, and the
      dinitrofluorobenzene-induced delayed-type hypersensitivity model. Psoriasis is an
      autoimmune disease that affects about 2% of the world population. Many treatments
      have been reported with varying degrees of efficacy. A topical bortezomib
      formulation was developed to minimize systemic exposure. Its tolerability was
      investigated in a topical imiquimod (IMQ)-induced psoriasis model. Daily
      application of IMQ on mouse skin induced inflamed scaly skin lesions resembling
      plaque-type psoriasis. Fatality was observed in the 1-mg/ml dose group. At 0.1
      and 0.01 mg/ml, bortezomib potentiated IMQ-induced erythema, scaling, skin
      thickening, and caused necrotic lesions. Lower doses had no effect on the
      clinical observations. Histologically, bortezomib dose-dependently increased
      parakeratosis, hyperkeratosis, acanthosis, and inflammatory cell infiltration.
      This study demonstrated that topical bortezomib is not suitable for the treatment
      of psoriasis.

PMID- 21865768
TI  - Glycerophosphate does not interact with components of parenteral nutrition.
AB  - BACKGROUND/AIMS: The primary objective of this study was to determine and compare
      the pharmacokinetic (PK) profiles of inorganic phosphate in the serum after
      continuous administration of pure glycerophosphate and glycerophosphate contained
      in total parenteral nutrition (TPN) emulsions. This approach was selected to
      identify potential PK interactions between TPN components and glycerophosphate.
      METHODS: The serum PK profile of inorganic phosphate after continuous intravenous
      administration of a sodium glycerophosphate containing TPN emulsion was
      determined in 10 healthy, white (5 male/5 female) volunteers. A pure sodium
      glycerophosphate formulation served as reference. Standard criteria of
      bioequivalence were applied. Subjects were enrolled in the double-blinded study
      and were randomly allocated to receive the test and reference preparations on two
      occasions in a 2-sequence crossover study design. The volunteers received 1/3 of
      the maximum recommended body weight- (BW) adjusted intravenous daily dosage (13.3
      ml/kg BW) of the test drug over a period of 8 h. The amount of total phosphate
      (0.101 mmol/kg) and duration of administration were identical for the test and
      reference drugs. Study days were separated by washout periods of at least 88 h.
      Serum concentrations of total inorganic phosphate were measured serially over a
      36-hour period using a validated method. A statistical mixed ANOVA, based on
      population averages, was used for testing bioequivalence between these study
      preparations. RESULTS: The 90% confidence intervals (90% CIs) of inorganic
      phosphate in serum were calculated for the test/reference ratios of the area
      under the time-concentration curve from time 0 to 36 h (AUC0-36), the maximum
      concentration (C(max)) and the concentration 5 min before the end of infusion
      (C(ss)) for a bioequivalence range from 0.80 to 1.25. The mean test/reference
      ratios fell completely within the 90% CIs with values of 1.016 (90% CI 1.005
      1.028), 1.013 (90% CI 0.981-1.047) and 0.932 (90% CI 0.886-0.980) for AUC(0-36),
      C(max) and C(ss), respectively. In total, 3 mild adverse events in the reference
      group were detected after starting intravenous infusion, while no adverse events
      were observed in the test group after treatment. CONCLUSION: Primary PK
      parameters were within the defined bioequivalence range of 0.8-1.25. Thus,
      inorganic phosphate levels were essentially similar between the two
      investigational medicinal products tested in the present study. These findings
      confirm the concept that nutritional components of the test drug do not
      significantly interact with glycerophosphate. The two study preparations proved
      to be safe during the investigation.

PMID- 21865769
TI  - Pharmacokinetics and tolerability of almorexant in Japanese and Caucasian healthy
      male subjects.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the pharmacokinetics and
      tolerability of single doses of the dual orexin receptor antagonist almorexant in
      Japanese and Caucasian healthy male subjects (n = 10 in each group, body weight
      matched +/-5%). METHODS: Almorexant (200 mg) was administered in the morning in
      the fasted state. The pharmacokinetic parameters of almorexant were calculated by
      noncompartmental analysis from the plasma concentration data. RESULTS: The
      pharmacokinetics of almorexant in Japanese and Caucasian subjects were similar.
      The plasma concentration-time profile of almorexant was characterized by a rapid
      absorption and disposition. Peak plasma concentrations (C(max)) were reached at
      approximately 1.0 h in both ethnic groups. C(max) was 13% lower (ratio of
      geometric means [90% CI]: 0.87 [0.53, 1.43]), and the total exposure (AUC(0
      )infinity) was 15% lower (0.85 [0.54, 1.35]) in the Japanese subjects. There was
      no difference in the geometric mean ratio for t(1/2) between the two ethnic
      groups (1.03 [0.84, 1.25]). Almorexant was well tolerated in both ethnic groups.
      CONCLUSION: The pharmacokinetics and tolerability profiles of almorexant in
      Japanese and Caucasian healthy male subjects are similar. No dose adjustments for
      clinical studies with almorexant in Japanese subjects appear to be needed.

PMID- 21865770
TI  - Definition of high-performance membranes - from the clinical point of view.
AB  - Global knowledge of the molecular target of uremic toxins (UTs) was significantly
      different in the 1980s than it is now. In 1971, Babb et al. hypothesized that UTs
      such as neurotoxin existed in mid-sized molecules ranging from 300 to 3,000 Da.
      In the 1980s, larger molecular weight substances > 5,000 Da were targeted for
      removal, as well as small and medium size toxins in Japan, while urea was
      considered a surrogate marker of UTs, and Kt/V for urea was used as a measure of
      dialysis dose in the USA. In Japan, albumin-bound toxins in addition to low
      molecular-weight proteins were targeted for removal as glomerular filtration in
      the normal kidney. As binding capacity of albumin is significantly lowered and,
      on the other hand, the alpha-helical content of albumin also lowered in uremic
      patients because of binding of UTs to albumin, a small amount of albumin should
      be removed to stimulate the synthesis of new albumin. KF101 C-2 (EVAL) used as a
      high-performance dialysis membrane (HPM) at the first step, in which
      approximately 7 g of albumin is removed per dialysis session. It resulted in
      lowered plasma albumin levels in hemodialysis patients, although accumulated
      levels of low-molecular-weight proteins were significantly lowered. Therefore,
      the Japanese Society of Dialysis Therapy has recommended limitation of albumin
      removal to < 3 g/session by the second generation of HPMs. Many different HPMs
      have been developed since the Japanese Society of HPM was first organized in
      1985. Approximately 98% of the dialyzers used in Japan employ HPMs. New
      technology is required to suppress fouling on the surface and in the pores of
      HPMs. This would maintain permeation of inflammatory cytokines during dialysis
      sessions.

PMID- 21865771
TI  - Solute removal efficiency and biocompatibility of the high-performance membrane -
      from engineering points of view.
AB  - Two major prerequisites of high-performance dialysis membranes are superior
      biocompatibility and high removal efficiency of pathogenic substances of large
      molecular size. In this article, we present a review, in the context of recent
      research results, of the solute removal efficiency and biocompatibility of the
      high-performance membrane. The former is discussed in terms of differences in
      separation properties arising from the constituent materials, the dialysis
      membrane structures, internal filtration-accelerated dialyzers, optimization of
      the dialysis fluid flow, and solute removal by adsorption, and the latter in
      terms of invasion of endotoxins present in dialysis fluid, antioxidant actions,
      and properties of the internal surface of dialysis membranes. We also discuss the
      main properties and problems of currently available high-performance dialysis
      membranes. While the solute removal efficiency of high-performance dialysis
      membranes is already mostly satisfactory and no further significant improvements
      are expected, except in relation to the fractioning properties (selectivity),
      there is much scope for improvement in the biocompatibility of dialysis
      membranes. It is important that ultrahigh-performance dialysis membranes of
      superior biocompatibility are developed based on the results of basic studies
      carried out from the engineering point of view, reports from the manufacturers,
      and clinical outcomes.

PMID- 21865772
TI  - Biocompatible characteristics of high-performance membranes.
AB  - Interactions of blood with hemodialysis membranes induce activation of blood
      factors that may cause adverse clinical outcomes in hemodialysis patients. The
      biocompatibility of a hemodialysis membrane is determined by the change in blood
      factors induced by blood interactions, and it is important that these
      interactions are mild and well tolerated by dialysis patients. Bioincompatible
      membranes that activate the complement system and accelerate cytokine production
      by monocytes may lead to chronic inflammation, dialysis-related amyloidosis,
      malnutrition, and atherosclerosis. Contact activation by a bioincompatible
      membrane may also induce an anaphylactoid reaction via bradykinin production.
      Thus, high-performance membranes should have both the high permeability to uremic
      substances shown by the glomerular basement membrane and the good
      biocompatibility of glomerular endothelial cells.

PMID- 21865773
TI  - Selection guidelines for high-performance membrane.
AB  - The fundamental concept for the selection of high-performance membrane is based
      on solute removal capability and biocompatibility. From this principle, the
      selection guidelines for high-performance membrane are recommended as follows:
      (1) The currently available products do not provide coverage of the necessary
      'balance between solute removal and biocompatibility' in a single dialyzer for
      all the dialysis patients. Therefore, it is advisable to choose a high
      performance membrane taking into consideration the balance between the solute
      removal capacity necessary for the patient and the severity of complications that
      is considered a surrogate marker for biocompatibility. (2) There is an increasing
      demand in dialysis therapy for new biocompatibility indices such as 'reducing
      blood pressure variability during dialysis', 'decreasing oxidative stress' and
      'delaying the onset or progression of complications'. High-performance membranes
      developed to address these needs include the ethylene-co-vinyl alcohol copolymer
      (EVAL) (R) membrane, cellulose triacetate, polymethylmethacrylate, vitamin E
      coated polysulfone (PS) membrane, and PS membrane hemodiafiltration filter.

PMID- 21865774
TI  - Preferred performance of the high-performance membrane in the case of online
      hemodiafiltration.
AB  - High-performance membrane (HPM) dialyzers have become commonly used in online
      hemodiafiltration (ol-HDF). HPM dialyzers with a markedly improved function of
      removing high-molecular solutes have appeared, but excessive albumin loss often
      occurs using these. Higher albumin loss was observed when these protein-permeable
      dialyzers were used for post-dilution ol-HDF. When albumin loss is regarded as
      the criterion, dialyzers with a 0.5 g or lower albumin loss in the hemodialysis
      mode should be used for post-dilution HDF, whereas those with a 2 g or greater
      albumin loss should be selected for pre-dilution HDF. The performance of recent
      HPM dialyzers has been markedly developed, and equivalent removal efficiency can
      now be achieved with non-ol-HDF. To demonstrate the efficacy of ol-HDF, it is
      necessary to compare hemodialysis and ol-HDF using a type V dialyzer (beta(2)
      microglobulin clearance >=70 ml/min) classified in Japan, and re-investigate the
      significance of removing high-molecular solutes larger than beta(2)-microglobulin
      and protein-bound solutes.

PMID- 21865775
TI  - Preferred dialysis fluid for the high-performance membrane.
AB  - In the present study, we investigated the effect of hemodialysis (HD) with high
      performance membrane filter (HPM-HD) using acetate-free bicarbonate dialysis
      (AFD) fluid on bioincompatibility as represented by inflammatory markers in
      patients undergoing maintenance HD therapy and compared it with conventional
      acetate-containing bicarbonate dialysis (ACD) fluid. A total of 36 maintenance HD
      patients were registered for study during the 4-month study period (22 males and
      14 females, aged 63.5 +/- 10.2 years, mean duration of dialysis 12.2 +/- 8.6
      years, chronic glomerular nephritis in 27 patients, diabetic nephropathy in 6
      patients, and nephrosclerosis in 3 patients). These patients were subjected to
      ACD for the first 2 months followed by AFD fluid for the latter 2 months.
      Predialysis blood pH and bicarbonate were examined after each of the first and
      latter 2-month period. Blood variables of C-reactive protein (CRP) and
      interleukin-6 (IL-6) or fetuin-A were also determined. The filters (membrane
      surface area, raw material), the conditions of HD (blood flow rate, dialysate
      flow rate, dialysis time, dry weight) and drug regimen including erythrocyte
      simulating agent (drug type, dosage) were unchanged throughout the study. There
      appeared to be significantly higher levels of predialysis blood pH and
      bicarbonate in the AFD phase than in the ACD phase. Blood CRP and IL-6 levels
      were significantly decreased in the AFD group as compared with those seen in the
      ACD group. From these results, it can be suggested that HPM-HD using AFD fluid
      contributes to correcting metabolic acidosis and alleviating microinflammation in
      HD patients.

PMID- 21865776
TI  - Required water quality for the use of high-performance membranes.
AB  - The clinical benefits of high-performance membrane (HPM) dialyzers have often
      been reported since the advent of the synthetic polyacrylonitrile dialysis
      membrane. HPMs, which have high water permeability, eliminate a wide spectrum of
      uremic toxins, and offer excellent biocompatibility, are now essential for
      hemodialysis, hemofiltration, and hemodiafiltration. For HPMs whose mean pore
      size is enlarged to secure better dialysis membrane performance, however, the
      dialyzing fluid must be highly purified to prevent contamination. Blood
      purification therapies using highly purified dialyzing fluid and HPM are expected
      to improve the prognosis of future patients undergoing dialysis.

PMID- 21865777
TI  - Clinical outcomes of the high-performance membrane dialyzer.
AB  - HPM (high-performance membrane or high-flux membrane) has better biocompatibility
      and higher capacity to remove retention solutes of large molecular weight, which
      has been proven to be toxic especially to cardiovascular and skeletal organs. To
      date, several non-randomized observational studies have shown a reduction in
      morbidity and mortality in HPM-treated patients compared with low-flux
      conventional membrane. Meanwhile, two randomized controlled trials were unable to
      reveal the superiority of high-flux membrane in survival of all-cause mortality,
      but suggested a significant benefit by subgroup analyses or post-hoc analyses in
      patients with diabetes, hypoalbuminemia and long duration of prior dialysis.
      Thus, the results of the published studies are conflicting and it still cannot be
      explained whether the effect is based on the biocompatibility of the membrane or
      on the differences in the clearance of middle molecules, or on the
      microbiological purity of dialysate which improved simultaneously with the flux
      increment. As survival outcome might be determined by additional multiple
      confounding factors, dialysis-related or non-dialysis-related, investigations to
      control them are difficult to perform. Although the clinical results are non
      conclusive and it is still unanswered how much large molecule removal is required
      to improve outcomes in routine clinical practice, there is a considerable amount
      of biological plausibility for high-flux dialysis or middle molecule removal.
      Further trials will be required to confirm what patient group benefits the most,
      the magnitude of advantages and how large the molecules are and how much molecule
      removal is acceptable using advanced high-performance dialyzers. Dispersing
      hazardous effects by a low-quality therapy should be taken more seriously than
      practicing a high-quality therapy of uncertain superiority.

PMID- 21865778
TI  - Endotoxin and bacterial level of dialysate fluid quality.
AB  - For dialysis fluid quality criteria, several dialysis centers in Japan have put
      great effort into keeping endotoxin (ET) levels low, although in many countries
      the bacterial count measurement for dialysis fluid is widely used. The
      International Organization for Standardization (ISO) suggests an ET and bacterial
      level for dialysate fluid quality, and Japan currently also measures the
      bacterial count. Each country presses forward to revise their domestic criteria
      based on ISO suggestions. In some Japanese cities, guidelines are currently made
      for dialysate fluid quality control by referring to ISO values. In many countries
      it is necessary to push forward these domestic guidelines to hemodialysis centers
      to keep a low level of ET and bacteria. As one of several actual data, we will
      describe the ET concentration and bacterial count of dialysis fluid in many
      Japanese dialysis centers to make clear the relation between ET level and
      bacterial count.

PMID- 21865779
TI  - Albumin loss under the use of the high-performance membrane.
AB  - Beta-2-microglobulin (beta(2)M) clearance has been improved in recent dialysis
      membranes and minimum albumin leakage has been achieved in most membranes today
      since dialysis membranes are now classified by beta(2)M clearance in terms of the
      reimbursement by health insurance. Kawanishi et al. suggested that 'the desirable
      albumin leakage in one treatment is less than 4 g '. Function classification type
      IV or type V dialysis membranes have leakages as low as 3 g, while most resulted
      in < 1 g leakage. However, some high-performance membranes (HPMs) have around 8 g
      of leakage, which requires further study of the clinical efficacy using such
      dialysis membranes. The comparison of albumin leakage in one dialysis treatment
      (4 h: blood flow volume of 250 ml/min) revealed that PES-210D has an
      overwhelmingly high albumin leakage of 7.69 +/- 1.01 g. The data were without any
      significant difference between the PES-D membrane user group and the non-PES-D
      membrane user group for hemoglobin, hematocrit, beta(2)M protein, catabolic rate,
      body mass index, and muscle mass. However, the PES-D membrane user group had a
      significantly lower number of hospitalizations and other complication events.
      When comparing the event contents, the PES-D membrane user group had no cardiac
      failure and lower DRA, however it had more vascular access problems. In normal
      renal function, approximately 10 g of albumin is filtered in the glomerulus per
      day, decomposed in the renal tubule and reabsorbed as amino acid, and re
      synthesized into albumin in the liver. On the contrary, in dialysis patients,
      albumin that is bound to biologically active substances and/or the oxidized form
      of albumin that has lost its antioxidant effect cannot be filtered from the
      kidney and accumulate. Therefore, the idea regarding albumin leakage is to remove
      biologically active substances that bind to albumin and function as uremic toxin,
      remove albumin without the antioxidant effect, and facilitate synthesis of new
      albumin with an antioxidant effect.

PMID- 21865781
TI  - Mass transfer mechanisms in high-performance membrane dialyzers.
AB  - Four dialyzers with super-high-flux membrane or high-performance membrane (HPM)
      with varying packing density of the hollow fiber (PDF) from 29.6 to 53.1% were
      investigated in aqueous in vitro experiments for the purpose of identifying the
      mass transfer mechanism for three test solutes. Clearances for relatively small
      test solutes (creatinine and vitamin B(12)) slowly increased with PDF and reached
      plateau since mass transfer mechanism of these solutes was diffusion limited.
      However, since unlike classic high-flux dialyzers a considerable amount of
      internal filtration ( > 20 ml/min) should occur in super-high-flux dialyzers even
      under relatively reduced blood and dialysis fluid flow rates, Q(B) = 200 ml/min
      and Q(D) = 500 ml/min, it should contribute to enhance the rate of mass transfer
      especially for those solutes that cannot be easily removed by diffusion, such as
      beta(2)-microglobulin or even larger toxic substances. For dialyzers with the HPM
      a module design becomes even more important for developing novel commercial
      products.

PMID- 21865780
TI  - Choice of modality with the use of high-performance membrane and evaluation for
      clinical effects.
AB  - The golden target for dialysis therapy should be to guarantee longer survival and
      to give a higher quality of life without dialysis-related complications. In order
      to achieve this target, the choice of dialysis modality and membrane is essential
      but we have not yet established what the best choice for a dialysis modality and
      membrane are. Generally, we choose a dialysis modality for better solute removal
      and better biocompatibility. In this issue we would like to propose that the
      patients' preference for dialysis therapy is a useful parameter in prescribing
      the dialysis modality. In our recent experience, chronic dialysis patients have
      had preferences on a dialysis modality and membrane, those being PMMA, EVAL, AN
      69 and pre-dilution online HDF. These modalities could relieve them of
      uncomfortable dialysis-related symptoms such as insomnia, itchiness,
      irritability, and so on. Other characteristics of these modalities are of a
      nutritional advantage, a broad removal pattern of uremic toxins including low
      molecular-weight protein and protein-bound uremic toxins, and good
      biocompatibility free from chemical components of dialysis membrane. In
      conclusion, patients' symptoms could be a useful parameter to choose a dialysis
      modality and membrane.

PMID- 21865782
TI  - Fluid and solute transfer characteristics in a dialyzer with a high-performance
      membrane.
AB  - To date, many types of high-flux dialyzers with high-performance membranes have
      been developed. They seem to have a higher internal filtration flow rate (Q(IF))
      because of a higher ultrafiltration coefficient. In the health reimbursement
      system in Japan, commercially available dialyzers are categorized into five types
      based on their beta(2)-microglobulin clearance (K(BMG)) values. Although the
      K(BMG) value was not correlated strongly with the Q(IF) value for 26 types of
      commercially available dialyzers, almost all the dialyzers with a higher Q(IF)
      value had a higher KBMG value. These dialyzers seem to have a higher convective
      transport because of internal filtration in addition to diffusive transport. We
      measured the blood flow velocity in a cross-sectional plane of the dialyzer using
      pulse Doppler ultra-sonography to evaluate QIF. It is a useful method for the
      bedside monitoring because it is noninvasive to the patient and produces reliable
      data with a higher reproducibility. On the other hand, membrane fouling occurs
      more easily in higher Q(IF) dialyzers, compared with conventional dialyzers,
      because of the higher degree of membrane fouling. Internal filtration-enhanced
      hemodialysis (IFEHD) using these dialyzers, therefore, has the advantage of
      increasing solute removal efficiency by enhancing convective transport and the
      simultaneous disadvantage of decreasing solute removal efficiency by causing
      membrane fouling. Thus, IFEHD treatment should be performed using a dialyzer with
      a high-performance membrane to ensure that the advantage is superior to the
      disadvantage.

PMID- 21865783
TI  - Contribution of polysulfone membranes to the success of convective dialysis
      therapies.
AB  - The majority of patients with chronic kidney disease are currently treated with
      dialyzers containing synthetic membranes. Of all the dialysis membranes made from
      these polymers, 93% are from the parent polyarylsulfone family of which 71% are
      from polysulfone (PSu) and 22% from polyethersulfone. The preference of
      nephrologists for PSu dialyzers signifies their versatility in terms of meeting
      the solute and fluid removal demands for all treatment modalities (low-and high
      flux dialysis, online hemodiafiltration, hemofiltration). The unprecedented
      success and widespread usage of PSu membranes is attributed, in addition to
      efficient removal of a broad spectrum of uremic toxins, to other criteria
      required of modern dialysis therapies. Namely, effective endotoxin retention
      capacity, pronounced intrinsic biocompatibility and low cytotoxicity are factors
      which all contribute to minimal adverse clinical sequelae. Furthermore, PSu by
      virtue of its high thermal stability can be sterilized with steam, the preferred
      mode of sterilization as it does not have the disadvantages associated with other
      sterilization methods. However, there are significant differences between
      membranes made from PSu due to differences in membrane polymer recipes and
      manufacturing technologies. Although PSu may be the main constituent, these
      membranes are blended with other polymers, e.g. hydrophilizing agents, such as
      polyvinylpyrrolidone to give each membrane its characteristic profile. The
      relative amounts of the two (or more) co-polymers as well as the spinning
      conditions provide a fingerprint of each membrane in terms of solute separation
      characteristics, biocompatibility, cytotoxicity or endotoxin retention
      capabilities. PSu membrane-based dialyzers thus fulfill the crucial therapy
      requirements of current treatment modalities to varying extents. Thereby,
      different effects towards patient outcomes and treatment safety are achieved.

PMID- 21865785
TI  - Polyethersulfone as a high-performance membrane.
AB  - Polyethersulfone as base material has proven its suitability for synthetic
      dialysis membranes since more than one decade. Recently, a new generation of high
      performance polyethersulfone membranes has been introduced, which are the result
      of an advanced spinning process. They are characterized by an improved
      permselectivity due to a more homogenous and dense pore size distribution. These
      innovative membranes achieve an outstanding middle molecule removal at low
      albumin loss and have best biocompatibility characteristics. Provided that the
      albumin permeability is low, the pyrogen retention capability is on a par with
      the best references. Overall, polyethersulfone high-performance membranes are
      highly efficient, biocompatible, safe and suited for all current dialysis
      procedures.

PMID- 21865784
TI  - AN69: Evolution of the world's first high permeability membrane.
AB  - In response to a request from the French government, Rhone-Poulenc started
      development of a synthetic membrane for dialysis in 1969. When used for patients
      the new membrane, AN69, showed improved efficiency and clinical outcome.
      Treatment times could be reduced, peripheral neuropathy improved and patients
      expressed improved quality of life. This was the introduction of high-flux,
      volume-controlled dialysis. The polymer used for the AN69 membrane is a copolymer
      of acrylonitrile and sodium methallylsulfonate, specially selected for the
      dialysis application. Contrary to most synthetic membranes AN69 is hydrophilic,
      because the numerous sulfonate groups attract water and create a hydrogel
      structure which provides high diffusive and hydraulic permeability. In the AN69
      membrane the microstructure and the chemical composition offer a unique context
      for bulk adsorption of low-molecular-weight proteins, the high water content of
      the hydrogel making the polymer chains easily accessible. The highly specific
      adsorptive properties - limited on the surface and favored in the membrane
      structure and with high specificity for basic, medium-sized proteins -
      distinguish AN69 from other synthetic high-flux membranes as well as from other
      so-called adsorptive membranes in the field of dialysis. Since its creation in
      the early 1970s the AN69 membrane has evolved to meet the requirements and
      challenges of dialysis therapy. Still the basic characteristics of high
      permeability to fluid and to a wide range of relevant uremic retention products
      combined with excellent biocompatibility, whether measured by traditional or
      novel indicators, have remained the hallmark of the membrane. The unique
      adsorptive capacity has provided a base for further development. The latest
      version of AN69, HeprAN, has heparin grafting on the inner surface and enhanced
      adsorption of bacterial products on the outer surface. Modern versions of AN69
      are today used in hemodialysis and contemporary modes of convective therapies for
      a large number of chronic as well as acute renal patients around the world.

PMID- 21865786
TI  - Polymethylmethacrylate membrane with a series of serendipity.
AB  - Forty years have passed since the polymethylmethacrylate (PMMA) membrane was
      first developed. This article reviews its history and explains its longevity. The
      membrane was developed through application of a stereocomplex phenomenon that is
      observed upon mixture of isotactic and syndiotactic PMMA polymers. Filtryzer(TM)
      B1 and B2 were approved in Japan in 1977. B1 was the pioneer high-performance
      membrane model and B2 was a model that simulated a low-flux cellulosic membrane.
      The development of B1 led to the development of the dialysis machine with an
      ultrafiltration rate (UFR)-controlling function because the UFR of B1 was too
      high to control using transmembrane pressure control. B1 was used not only as a
      dialyzer but also as a hemodiafilter by combination with a UFR controller.
      Biocompatibility of the dialysis membrane, complement activation and/or transient
      leukopenia was studied with B2. Cooperative studies between Niigata University
      and Toray resulted in Gejyo's finding regarding the harmfulness of beta(2)
      microglobulin (BMG). Long-term follow-up of patients dialyzed using the BK
      membrane revealed that plasma BMG levels were significantly low and that the
      occurrence ratio of carpal tunnel syndrome was suppressed. These results were
      obtained by the adsorptive removal of BMG onto a PMMA membrane. Several papers
      have discussed new aspects in succession mainly based on clinical experiences
      that were not aimed at a development stage, i.e. they were kinds of serendipity.
      For the BK-F membrane with the largest pore size, this includes anemia and
      removal or modification of furancarboxylic acid, homocysteine, pentosidine and
      soluble CD40. For the BG membrane with a slightly anionic component, this
      includes pruritus and removal of free immunoglobulin light chains. Even patients'
      prognoses may be modified by the use of PMMA membrane. The mechanisms of these
      findings have been clarified bit by bit and the membrane will further open new
      frontiers in dialysis treatment.

PMID- 21865787
TI  - Polyester polymer alloy as a high-performance membrane.
AB  - Polyester polymer alloy (PEPA) membrane is developed as a synthetic
      polymermembrane. It consists of two polymers - polyethersulfone (PES) and
      polyarylate (PAR).The pore size in membrane can be controlled by a blend ratio of
      PES and PAR. One unique characteristic is that PEPA membrane has three layers of
      a skin layer on the inner surface, a porous layer in the membrane, and a skin
      layer on the outer surface, respectively. The permeability of water and
      substances is controlled by the skin layer on the inner surface. PEPA membrane
      dialyzer can be adequately considered as a high-performance dialyzer.
      Furthermore, the skin layer on the outer surface can block endotoxin from the
      dialysis fluid side. PEPA membrane can therefore be used as an endotoxin
      retentive filter. The other unique characteristic is that each amount of albumin
      loss or beta2-microglobulin removal can be controlled by an additive amount of
      polyvinylpyrrolidone. This means that the PEPA dialyzer can be clinically used to
      meet the conditions of the patient.

PMID- 21865788
TI  - Cellulose triacetate as a high-performance membrane.
AB  - The cellulose triacetate membrane is one of the typical high-performance
      membranes. Cellulose triacetate is a plastic material manufactured from
      cellulose. The hydroxyl group of cellulose is chemically substituted for the
      carboxyl group. Therefore, its characteristics are quite different from
      cellulose. The cellulose triacetate membrane has a homogeneous membrane
      structure. It can be produced with a wide range of permeability, from low-flux
      performance to super high-flux performance. Because the thickness of the membrane
      is thin, and flow distribution of the dialysate (due to the moire structure) is
      uniform, this enables the development of a dialyzer with high diffusive
      efficiency. Recently, this new product, improved through a sieving process,
      produced a uniform pore size distribution. As for the dialyzer, through
      sterilization by gamma-rays with the absence of oxygen, now enables long-term
      safety of the product. Several clinical improvements have been reported, such as
      high antithrombus, the improvement of lipid metabolism and the reduction of
      biomarkers. Thus, continuous membrane development is desired, made of safe and
      stable cellulose triacetate material.

PMID- 21865789
TI  - Ethylene vinyl alcohol co-polymer as a high-performance membrane: an EVOH
      membrane with excellent biocompatibility.
AB  - Over the last few years, with an increase in the number of patients receiving
      long-term dialysis and elderly patients on dialysis, the frequency of
      cardiovascular complications and complications associated with long-term dialysis
      have increased sharply. As a result, dialysis treatment must be capable of
      reducing oxidative stress and mitigating the inflammatory response. The ethylene
      vinyl alcohol (EVOH) co-polymer is a hydrophilic and uncharged synthetic polymer
      blend. EVOH membranes have a smooth surface and retain structural water, so they
      adsorb few plasma proteins. Dialysis using an EVOH membrane results in minimal
      platelet activation and little generation of reactive oxygen species by activated
      neutrophils. Consequently, patients have good peripheral circulation. As a
      result, fluid containing uremic toxins moves readily from the intracellular
      compartment to the intravascular compartment through the interstitial space. In
      addition, these membranes cause minimal activation of coagulation during
      dialysis; therefore, genes encoding monocyte chemoattractant protein-1 and
      inflammatory cytokines (e.g. IL-6) are expressed at low levels. Thus, treatment
      involving an EVOH membrane can be expected to help alleviate cardiovascular
      complications and complications of dialysis.

PMID- 21865790
TI  - Sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane
      (SHEDD-fA) in the treatment of patients with severe sepsis.
AB  - Sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane
      (SHEDD-fA) is an effective, intensive modality for sepsis treatment. Here we
      describe the effectiveness of SHEDD-fA, which makes the best use of three
      principles: dialysis, filtration and adsorption, for mediator removal in the
      treatment of severe sepsis. SHEDD-fA was initiated after adequate fluid
      resuscitation and catecholamine support had been provided. A large (2.1 m(2))
      polymethylmethacrylate membrane dialyzer was placed in the blood circuit.
      Operation conditions were as follows: blood flow rate 150 ml/min, filtration rate
      1,500 ml/h (post-dilution), and dialysate flow rate 300-500 ml/min over 8-12 h
      daily. 55 consecutive patients with severe sepsis were studied. The following
      results were obtained: pressure catecholamine index significantly decreased at 3
      h after initiation of septic shock, PaO(2)/F(IO2) significantly increased at 1 h
      after initiation of septic acute respiratory distress syndrome, a significant
      decrease in interleukin (IL)-6 level for 3 days was observed, and IL-6 was
      effectively adsorbed in one pass through the filter. The average sequential organ
      failure assessment score of patients was 10.1 and the mortality at 28 days was
      16.4% (46 survived, 9 died). Because SHEDD-fA is an intensive and high-efficiency
      modality, removal of useful drugs or nutrients may be observed. Despite the fact
      that removal of useful substances cannot be ignored, we believe that an
      appropriate stage or timing can be identified so that we can avoid a vicious
      cycle and use blood purification with effective diffusion, filtration and
      adsorption. We demonstrate that SHEDD-fA may be an effective, intensive modality
      for the treatment of patients with severe sepsis and is a possible modality for
      cytokine modulation therapy.

PMID- 21865791
TI  - Comparison of efficacy between continuous hemodiafiltration with a PMMA high
      performance membrane dialyzer and a PAN membrane hemofilter in the treatment of
      septic shock patients with acute renal failure.
AB  - The aim of this study was to investigate whether continuous hemodiafiltration
      (CHDF) with a high-performance membrane dialyzer made of polymethylmethacrylate
      (PMMA-CHDF) in the treatment of septic shock patients with acute renal failure
      (ARF) is clinically relevant. 30 patients were treated with PMMA-CHDF. 13
      patients treated with CHDF used a hemofilter made of polyacrylonitrile membrane
      (PAN-CHDF). Systolic blood pressure significantly increased in the PMMA-CHDF
      group following 24 h of treatment (p < 0.01), whereas it did not improve in the
      PAN-CHDF group. Urine volume significantly increased in the PMMA-CHDF group
      following 24 h of treatment which was more than in the PAN-CHDF group (p < 0.05).
      28-day survival was 83.3% in the PMMA-CHDF group and 30.8% in the PAN-CHDF group,
      respectively (p < 0.01). We can assume that PMMA-CHDF in the treatment of septic
      shock patients with ARF is clinically relevant.

PMID- 21865792
TI  - Commercially available high-performance membrane dialyzers and several special
      kinds on the Japanese market (as of April 30, 2011).

PMID- 21865793
TI  - History of lasers in dermatology.
AB  - In the 1950s, based on the theory of stimulating radiant energy published by
      Albert Einstein in 1916, the collaboration of physicists and electrical
      engineers, searching for monochromatic radiation to study the spectra of
      molecules, led to the invention of the first laser in 1960. Ophthalmologists and
      dermatologists were the first to study the biological effects and therapeutic
      possibilities of laser beams. The construction of new laser systems emitting
      energy at different wavelengths or with different durations, as well as the
      development of new concepts of the biomedical effects, led to its broad use in
      surgery in the treatment of vascular and pigmented lesions as well as cosmetic
      applications.

PMID- 21865794
TI  - Laser principles.
AB  - Since the construction of the first laser in the 1960s, the role that lasers play
      in various medical specialities, including dermatology, has steadily increased.
      However, within the last 2 decades, the technological advances and the use of
      lasers in the field of dermatology have virtually exploded. Many treatments have
      only become possible with the use of lasers. Especially in aesthetic medicine,
      lasers are an essential tool in the treatment armamentarium. Due to better
      research and understanding of the physics of light and skin, there is now a wide
      and increasing array of different lasers and devices to choose from. The proper
      laser selection for each indication and treatment requires a profound
      understanding of laser physics and the basic laser principles. Understanding
      these principles will allow the laser operator to obtain better results and help
      avoid complications. This chapter will give an in-depth overview of the physical
      principles relevant in cutaneous laser surgery.

PMID- 21865795
TI  - Laser-induced tissue reactions and dermatology.
AB  - Knowledge of laser tissue reactions and tissue properties allows the practitioner
      to tailor a treatment to an individual patient's need and goals. A laser's power,
      spot size and pulse duration may be manipulated to yield different tissue
      reactions. Five tissue reactions, each the result of varying laser pulse
      durations and energy densities, may be achieved. They are photochemical,
      photothermal, photoablation, plasma-induced ablation and photomechanical. Of
      these, photothermal reactions are most utilized in dermatology. When higher
      powered pulses are applied, tissue often undergoes multiple reactions
      simultaneously. An understanding of these reactions allows their effects to be
      predicted. In this chapter, the various reactions are reviewed, and the reactions
      caused by many of the most commonly used lasers in dermatology are discussed.

PMID- 21865796
TI  - Laser safety.
AB  - The use of lasers in medical practice has seen great expansion in the past
      decades. However, these devices may also pose a significant hazard. Laser hazards
      are generally divided into beam hazards and nonbeam hazards. Beam hazards inflict
      ocular and cutaneous injury, whereas nonbeam hazards stem from the laser device
      itself or its interaction with materials within the surgical environment. The
      latter include laser plume hazards, fire hazards, and electrical hazards inherent
      in a high-voltage system that is a laser device. Therefore, a thorough
      understanding of these hazards along with methods to reduce their risk is of
      paramount importance in order to ensure maximal safety for the surgeon, the
      staff, and the patient.

PMID- 21865797
TI  - Ablative skin resurfacing.
AB  - Ablative skin resurfacing has remained the gold standard for treating photodamage
      and acne scars since the development of the first CO(2) lasers. CO(2) and Er:YAG
      lasers emit infrared light, which targets water resulting in tissue contraction
      and collagen formation. The first ablative laser systems created significant
      thermal damage resulting in unacceptably high rates of scarring and prolonged
      healing. Newer devices, such as high-energy pulsed lasers and fractional ablative
      lasers, are capable of achieving significant improvements with fewer side effects
      and shorter recovery times. While ablative resurfacing has become safer, careful
      patient selection is still important to avoid post-treatment scarring,
      dyspigmentation, and infections. Clinicians utilizing ablative devices need to be
      aware of possible side effects in order to maximize results and patient
      satisfaction. This chapter reviews the background of ablative lasers including
      the types of ablative lasers, mechanism of action, indications for ablative
      resurfacing, and possible side effects.

PMID- 21865798
TI  - Non-ablative lasers.
AB  - Non-ablative laser devices exert their effects by inducing dermal collagen
      remodeling while sparing the epidermis. The remodeling process is achieved by
      producing thermal energy in a controlled and precise fashion, which recruits
      fibroblasts and stimulates collagen production. Although these devices do not
      produce the same degree of improvement as traditional CO(2) or er:YAG resurfacing
      techniques, they are an excellent alternative for people seeking gradual
      aesthetic improvement with minimal downtime. They are also extremely well suited
      to patients with darker skin types. In this chapter, we review the various non
      ablative devices currently available on the market, with an emphasis on safety
      profiles and efficacy.

PMID- 21865799
TI  - Fractional photothermolysis.
AB  - The novel concept of 'fractional photothermolysis' was introduced to the market
      in 2003, and has since gained tremendous popularity and importance for numerous
      clinical indications. Its development and introduction were driven by the need
      for an effective yet safe and low-risk resurfacing technique, in contrast to the
      ablative and non-ablative lasers available at the time. The first device that was
      introduced to the market used non-ablative wavelengths. In 2007, the technology
      was further developed with ablative wavelengths leading to vaporization of
      tissue. This new technology has revolutionized the field of laser skin
      resurfacing and resulted in the development of numerous non-ablative and ablative
      fractional devices. There is little doubt that fractional technology is here to
      stay, as (when used properly) it allows the operator to obtain significant
      clinical results with minimal post-treatment recovery and hence fewer
      complications.

PMID- 21865800
TI  - Vascular lesions.
AB  - Advances in laser and light-based technology have increased their potential
      applications, safety and efficacy for the management of vascular lesions in
      dermatology. Light devices for vascular lesions include the variable-pulse 532 nm
      potassium titanyl phosphate laser, 577 to 595 nm pulsed dye laser, intense pulsed
      light devices, and 800 to 940 nm diode, long-pulse 755 nm alexandrite and 1,064
      nm Nd:YAG lasers. This review will discuss the various different laser and light
      based devices, and provide a focused treatment approach for the management of
      common congenital and acquired vascular lesions.

PMID- 21865801
TI  - Benign pigmented lesions.
AB  - Benign pigmented lesions are a frequent complaint in dermatological patients,
      especially those seeking advice and therapy in a laser or cosmetic practice.
      Significant advances in laser technology over the last decades now allow us to
      effectively and safely treat various benign pigmented lesions. However, a
      thorough understanding of the biology of the lesion to be treated, the physical
      properties of the lasers to be used, and laser-tissue interactions is crucial for
      a successful and safe treatment. This chapter will give an overview of the types
      of benign pigmented lesions that can be treated with lasers and the specific
      lasers used to treat them.

PMID- 21865802
TI  - Tattoo removal.
AB  - Over 50,000 new tattoos are placed each year in the United States. Studies
      estimate that 24% of American college students have tattoos and 10% of male
      American adults have a tattoo. The rising popularity of tattoos has spurred a
      corresponding increase in tattoo removal. Not all tattoos are placed
      intentionally or for aesthetic reasons though. Traumatic tattoos due to
      unintentional penetration of exogenous pigments can also occur, as well as the
      placement of medical tattoos to mark treatment boundaries, for example in
      radiation therapy. Protocols for tattoo removal have evolved over history. The
      first evidence of tattoo removal attempts was found in Egyptian mummies, dated to
      have lived 4,000 years BC. Ancient Greek writings describe tattoo removal with
      salt abrasion or with a paste containing cloves of white garlic mixed with
      Alexandrian cantharidin. With the advent of Q-switched lasers in the late 1960s,
      the outcomes of tattoo removal changed radically. In addition to their selective
      absorption by the pigment, the extremely short pulse duration of Q-switched
      lasers has made them the gold standard for tattoo removal.

PMID- 21865803
TI  - Hair removal.
AB  - Hair removal with optical devices has become a popular mainstream treatment that
      today is considered the most efficient method for the reduction of unwanted hair.
      Photothermal destruction of hair follicles constitutes the fundamental concept of
      hair removal with red and near-infrared wavelengths suitable for targeting
      follicular and hair shaft melanin: normal mode ruby laser (694 nm), normal mode
      alexandrite laser (755 nm), pulsed diode lasers (800, 810 nm), long-pulse Nd:YAG
      laser (1,064 nm), and intense pulsed light (IPL) sources (590-1,200 nm). The
      ideal patient has thick dark terminal hair, white skin, and a normal hormonal
      status. Currently, no method of lifelong permanent hair eradication is available,
      and it is important that patients have realistic expectations. Substantial
      evidence has been found for short-term hair removal efficacy of up to 6 months
      after treatment with the available systems. Evidence has been found for long-term
      hair removal efficacy beyond 6 months after repetitive treatments with
      alexandrite, diode, and long-pulse Nd:YAG lasers, whereas the current long-term
      evidence is sparse for IPL devices. Treatment parameters must be adjusted to
      patient skin type and chromophore. Longer wavelengths and cooling are safer for
      patients with darker skin types. Hair removal with lasers and IPL sources are
      generally safe treatment procedures when performed by properly educated
      operators. However, safety issues must be addressed since burns and adverse
      events do occur. New treatment procedures are evolving. Consumer-based treatments
      with portable home devices are rapidly evolving, and presently include low-level
      diode lasers and IPL devices.

PMID- 21865804
TI  - Photoaging.
AB  - Treatments for photoaging are commonly requested by cosmetic patients. Laser
      resurfacing treatment addresses the myriad aspects of photoaging, including fine
      rhytides, dyspigmentation, and abnormal texture. Recent developments in laser
      medicine--such as fractional resurfacing in both ablative and non-ablative
      wavelengths--have improved the safety and side effect profile of laser
      resurfacing. Both ablative and non-ablative wavelengths are effective. The use of
      lasers should be limited to experienced practitioners to minimize the risks of
      scarring, pigment alterations, and other unwanted effects.

PMID- 21865805
TI  - Scars.
AB  - Scars are usually classified into atrophic scars, hypertrophic scars, or keloids.
      A number of lasers, both with known and unknown mechanisms of action, have been
      investigated for improving the appearance of such scars, with variable outcomes.
      Currently, multiple lasers are being utilized for the treatment of scars. The 585
      nm pulsed dye laser is the gold standard of laser therapy for keloid and
      hypertrophic scars. The ablative lasers such as the CO(2) and Er:YAG lasers are
      best suited for atrophic scars. Non-ablative approaches have also become popular
      and are being widely used to achieve reduced downtimes yet still provide
      excellent outcomes. This chapter discusses these lasers and their role in scar
      improvement.

PMID- 21865806
TI  - Acne vulgaris.
AB  - Acne vulgaris is one of the most common dermatological diseases, and caused by a
      combination of pathogenetic factors including follicular hyperkeratosis,
      seborrhea, colonization with Propionibacteriumacnes and inflammatory phenomena.
      Various medical treatments address these causative factors, but they are not
      always well tolerated. In the last decades, there has been increased interest in
      laser and light-based treatments. These optical devices mainly target
      Propionibacteriumacnes by activating porphyrins produced by the bacterium,
      whereas some treatments directly lead to the destruction of sebaceous glands.
      Photodynamic therapy can enhance these effects through the prior application of a
      photosensitizing agent. Many laser and light-based treatments have shown
      excellent clinical results in the reduction of inflammatory acne lesions and
      improved acne severity. Although relapses are frequent, results can be improved
      by combination therapy with conventional medical treatments. Data of randomized
      controlled studies or studies with a split-face design are contradictory and
      difficult to compare. Furthermore, the cost of the treatments is often a limiting
      factor. In summary, some optical devices are an important additional tool in the
      treatment of patients with mainly inflammatory acne where conventional treatments
      are not well tolerated.

PMID- 21865807
TI  - Skin tightening.
AB  - Skin tightening describes the treatment of skin laxity via radiofrequency (RF),
      ultrasound, or light-based devices. Skin laxity on the face is manifested by
      progressive loss of skin elasticity, loosening of the connective tissue
      framework, and deepening of skin folds. This results in prominence of
      submandibular and submental tissues. Genetic factors (chronological aging) and
      extrinsic factors (ultraviolet radiation) both contribute to skin laxity. There
      are many RF, ultrasound, and light-based devices directed at treating skin
      laxity. All of these devices target and heat the dermis to induce collagen
      contraction. Heating of the dermis causes collagen denaturation and immediate
      collagen contraction in addition to long-term collagen remodeling. Via RF, light,
      or ultrasound, these skin tightening devices deliver heat to the dermis to create
      new collagen and induce skin tightening. This chapter will provide an overview of
      the various skin tightening devices.

PMID- 21865808
TI  - Special considerations for darker-skinned patients.
AB  - Today, lasers are being used to treat an increasing number of medical and
      aesthetic challenges with great success. However, the effects of laser treatments
      upon darker-skinned patients differ from those on Caucasians in several aspects;
      this makes their use not without risk. First of all, skin of color has a greater
      epidermal melanin content than Caucasian skin, and this increase in epidermal
      pigmentation acts as a competing chromophore. Furthermore, with epidermal melanin
      acting as a competing chromophore, the light dosage that reaches the actual
      target is reduced, and higher fluence is necessary to produce a desirable effect.
      Although effective cooling and longer wavelengths with decreased melanin
      absorption have been used, the treatment of patients with Fitzpatrick skin types
      > IV remains associated with a significant risk of side effects. Thus, careful
      selection of laser and light source parameters in conjunction with skin cooling
      are important in obtaining desirable clinical outcomes in ethnic skin.

PMID- 21865809
TI  - At-home laser and light-based devices.
AB  - With the advancement in laser technology, there has been a recent trend in laser
      and light devices towards 'do it yourself' at-home use. There has been an
      exponential growth in devices aimed at the treatment of acne, hair removal, and
      psoriasis. With the exception of the at-home UVB box and excimer lasers, these
      systems do not require a prescription and patients may purchase the systems as
      over-the-counter products. Medical treatment still remains the standard of care
      for most conditions, but these at-home devices play a significant role in the
      treatment of various conditions. Media and marketing have driven the popularity
      of these devices and have encouraged patients to try them out. Patients are
      attracted to at-home devices because of the one-time cost, ease of use,
      convenience, and privacy of use. Naturally, despite these devices being for at
      home use, there should be a level of caution adhered to when using any laser or
      light device.

PMID- 21865810
TI  - Intense pulsed light.
AB  - In addition to lasers, intense pulsed light (IPL) sources are widely used in
      medicine to treat various indications, such as vascular lesions, irregular
      pigmentation and hypertrichosis. In contrast to lasers, IPL systems are broadband
      flash lamps that emit polychromatic incoherent light ranging from visible to
      infrared (500-1,300 nm). Optical filters are used to tailor the polychromatic
      light to specific needs. As a broad range of wavelengths are delivered, treatment
      of multiple chromophores--including melanin, hemoglobin, water and collagen-
      within the same exposure is possible.

PMID- 21865811
TI  - Light-emitting diode.
AB  - Light-emitting diode (LED) photomodulation has become a recognized player in the
      world of lasers and light sources. It is used to treat a variety of clinical
      entities, including photorejuvenation, erythema-induced injury following laser
      and other cosmetic procedures, and acne vulgaris. Its use has increased and will
      increase further as our understanding of LED devices deepens.

PMID- 21865812
TI  - Photodynamic therapy.
AB  - Photodynamic therapy (PDT) utilizes a photosensitizer, a light source, and
      molecular oxygen to selectively destroy cells. In dermatology, the
      photosensitizers accumulate in non-melanoma skin cancer cells, actinically
      damaged skin cells and actinic keratoses (AK), and in the pilosebaceous units.
      This has forged great interest and clinical research towards utilizing PDT for
      the treatment of non-melanoma skin cancers, AK and associated photorejuvenation,
      and inflammatory acne vulgaris. Here, the evidence-based medicine supporting the
      use of PDT in the USA will be presented, and how we utilize PDT in our clinic
      will also be discussed. It is hoped that with this knowledge, more and more
      clinicians will feel comfortable using this therapy, thereby benefitting their
      patients to an even greater extent.

PMID- 21865813
TI  - Action plan for a healthy agriculture, healthy nutrition, healthy people.

PMID- 21865814
TI  - Keynote.

PMID- 21865815
TI  - Importance of the omega-6/omega-3 balance in health and disease: evolutionary
      aspects of diet.

PMID- 21865816
TI  - The omega-6/omega-3 fatty acid ratio in chronic diseases: animal models and
      molecular aspects.

PMID- 21865817
TI  - All PUFAs are not created equal: absence of CHD benefit specific to linoleic acid
      in randomized controlled trials and prospective observational cohorts.

PMID- 21865818
TI  - Stress and behavior: the role of nutrients with emphasis on omega-3 fatty acids.

PMID- 21865819
TI  - The current Greek diet and the omega-6/omega-3 balance: the Mediterranean diet
      score is inversely associated with the omega-6/omega-3 ratio.

PMID- 21865820
TI  - The Chilean diet and the omega-6/omega-3 balance.

PMID- 21865822
TI  - From French to Mediterranean diet: importance of the omega-6/omega-3 fatty acids
      ratio.

PMID- 21865821
TI  - From the Swedish to the Mediterranean diet and the omega-6/omega-3 balance.

PMID- 21865823
TI  - Epidemiological studies on cognition and the omega-6/omega-3 balance.

PMID- 21865824
TI  - Diet and mental health: an up-to-date analysis.

PMID- 21865825
TI  - The Okinawan diet: a modern view of an ancestral healthy lifestyle.

PMID- 21865826
TI  - New Cholesterol Guidelines for Longevity (2010).

PMID- 21865827
TI  - Update of French nutritional recommendations for fatty acids.

PMID- 21865828
TI  - Genetics of the adaptation to exercise.

PMID- 21865829
TI  - Genetic and nutritional interactions in cardiovascular disease.

PMID- 21865830
TI  - Dietary omega-3 fatty acids, genetic variation and risk of breast and prostate
      cancers.

PMID- 21865831
TI  - Global warming and cardiovascular health: mind the gap.

PMID- 21865832
TI  - Climate change and its impact on food and nutrition security and food safety in
      China.

PMID- 21865833
TI  - Climate change and its potential impact on the nutritional scenario in South-East
      Asia.

PMID- 21865834
TI  - Food and nutrition security in the Australia-New Zealand region: impact of
      climate change.

PMID- 21865835
TI  - 'Health-oriented agriculture' for nutritional security versus climate change
      risks in the Mediterranean Basin.

PMID- 21865836
TI  - Improving milk nutritional and environmental value with flaxseed-supplemented
      diets.

PMID- 21865837
TI  - The first carbon neutral extra virgin olive oil in the world!

PMID- 21865838
TI  - Urban agriculture and urban design.

PMID- 21865839
TI  - Healthy people and homes.

PMID- 21865840
TI  - Food industry response to nutritional studies.

PMID- 21865841
TI  - The art of applying science: creating a convergence of interests among producers,
      consumers, regulators and scientists.

PMID- 21865842
TI  - Role of government.

PMID- 21865843
TI  - Methods employed for induction and analysis of experimental myocardial infarction
      in mice.
AB  - Myocardial ischemia und subsequent reperfusion is followed by a complex sequence
      of pathophysiological responses involving inflammatory cell infiltration and
      cytokine release as well as postinfarction wound healing and myocardial tissue
      remodeling. With the development of gene targeted mice the contribution of
      individual gene products to the pathophysiology of myocardial ischemia and
      reperfusion can be defined leading to an increasing interest in the widely-used
      mouse model of myocardial infarction. This methological paper describes in detail
      the required equipment, surgical instruments, drugs and additional material, the
      methods of anesthesia and analgesia, the procedures involved in preparation of
      the animal, tracheotomy, intubation, thoracotomy, occlusion of the left
      descending artery, removal of the heart, determination of infarct size, analysis
      of cardiac functional parameters with echocardiography and magnetic resonance
      imaging (MRI) as well as determination of the morphological consequences
      utilizing gelatin zymography, histology and immunohistochemistry.

PMID- 21865845
TI  - Systemic heme oxygenase-1 transgenic overexpression aggravates pressure overload
      induced cardiac hypertrophy in mice.
AB  - BACKGROUND/AIMS: Heme oxygenase-1(HO-1) has been reported to protect against
      cardiac hypertrophy in cultured neonatal cardiomyocytes treated with HO-1
      inducer, cardiac specific HO-1 transgenic mice, or animals treated with HO-1
      inducer. The aim of the present study is to examine the effects of systemic HO-1
      transgenic overexpression on pressure overload-induced cardiac hypertrophy in
      mice. METHODS: Pressure-overload cardiac hypertrophy was induced by transverse
      aortic constriction (TAC) in WT (wild type) and systemic HO-1 transgenic
      overexpression (TG) mice. RESULTS: We found that systemic HO-1 transgenic
      overexpression aggravated pressure overload-induced cardiac hypertrophy. Pressure
      overload induced the more increases of heart weight/ body weigh index, left
      ventricular weight/ body weight index, beta-MHC protein expression, cardiac
      interstitial fibrosis in TG mice than in WT mice. Pressure-overload increased
      cardiac HO-1 protein expression in WT but not TG mice, but the cardiac HO-1
      protein level was still higher in TAC-treated TG mice than in TAC-treated WT
      mice. The basal cardiac calcineurin protein level in TG mice was lower than that
      in WT mice. Pressure-overload increased calcineurin protein expression in both WT
      and TG mice; however, pressure-overload induced more calcineurin protein
      expression in TG mice than in WT mice. CONCLUSION: This study shows for the first
      time that systemic HO-1 transgenic overexpression aggravates pressure overload
      induced cardiac hypertrophy.

PMID- 21865844
TI  - The cardioprotective effect of brief acidic reperfusion after ischemia in
      perfused rat hearts is not mimicked by inhibition of the Na(+)/H(+) exchanger
      NHE1.
AB  - BACKGROUND: Ischemic postconditioning (PostC), i.e. brief ischemia-reperfusion
      cycles before full reperfusion, is protective against cardiac
      ischemia/reperfusion (I/R) injury. Inhibition of the Na(+)/H(+) exchanger NHE1
      and delayed intracellular pH-normalization have been proposed to underlie
      protection by PostC. METHODS AND RESULTS: We used Langendorff perfused rat hearts
      exposed to 35 min global ischemia to show that 15 min acidic (pH 6.5) treatment
      at onset of reperfusion decreased infarct size and functional deterioration at
      least to the same extent as PostC. In contrast, NHE1 inhibition by EIPA was
      detrimental. To evaluate HL-1 atrial cardiomyocytes as a cellular model for
      PostC, we exposed the cells to simulated ischemia/reperfusion (I/R) mimicking
      that in perfused hearts. Necrosis and apoptosis induced by I/R were unaffected by
      15 min of pH 6.0 at onset of reperfusion. I/R increased the activity of c-Jun N
      terminal Kinase 1/2 (JNK1/2) and Akt, but not of p38 MAPK, with no further effect
      of acidic reperfusion or EIPA. CONCLUSION: In rat hearts, 15 min acidic
      reperfusion improves myocardial performance at least as much as does PostC,
      whereas NHE1 inhibition is detrimental. In contrast, in HL-1 cardiomyocytes,
      acidic reperfusion or NHE1 inhibition affect neither survival nor JNK1/2-, Akt-,
      and p38 MAPK activity after I/R, pointing to different mechanisms of damage and
      protection in these systems.

PMID- 21865846
TI  - The antiapoptotic effect of granulocyte colony-stimulating factor reduces infarct
      size and prevents heart failure development in rats.
AB  - BACKGROUND/AIM: Granulocyte colony-stimulating factor (G-CSF) reduces myocardial
      injury and improves cardiac function after myocardial infarction (MI). We
      investigated the early alterations provided by G-CSF and the chronic
      repercussions in infarcted rats. METHODS: Male Wistar rats (200-250g) received
      vehicle (MI) or G-CSF (MI-GCSF) (50 MUg/kg, sc) at 7, 3 and 1 days before MI
      surgery. Afterwards MI was produced and infarct size was measured 1 and 15 days
      after surgery. Expression of anti- and proapoptotic proteins was evaluated
      immediately before surgery. 24 hours after surgery, apoptotic nuclei were
      evaluated. Two weeks after MI, left ventricular (LV) function was evaluated,
      followed by in situ LV diastolic pressure-volume evaluation. RESULTS: Infarct
      size was decreased by 1 day pre-treatment before occlusion (36+/-2.8 vs. 44+/
      2.1% in MI; P<0.05) and remained reduced at 15 days after infarction (28+/-2.2
      vs. 36+/-1.4% in MI; P<0.05). G-CSF pretreatment increased Bcl-2 and Bcl-xL
      protein expression, but did not alter Bax in LV. Apoptotic nuclei were reduced by
      treatment (Sham: 0.46+/-0.42, MI: 15.5+/-2.43, MI-GCSF: 5.34+/-3.34%; P<0.05).
      Fifteen days after MI, cardiac function remained preserved in G-CSF pretreated
      rats. The LV dilation was reduced in MI-G-CSF group as compared to MI rats, being
      closely associated with infarct size. CONCLUSION: The early beneficial effects of
      G-CSF were essentials to preserve cardiac function at a chronic stage of
      myocardial infarction.

PMID- 21865847
TI  - Crucial role of phospholamban phosphorylation and S-nitrosylation in the negative
      lusitropism induced by 17beta-estradiol in the male rat heart.
AB  - BACKGROUND/AIMS: 17beta-estradiol (17betaE2) plays an important cardiovascular
      role by activating estrogen receptors (ER) alpha and ERbeta. Previous studies
      demonstrated that the novel estrogen G protein-coupled receptor (GPR30/GPER)
      mediates estrogen action in different tissues. We have recently shown in the rat
      heart that 17betaE2 elicits negative inotropism through ERalpha, ERbeta and
      GPR30, by triggering activation of ERK1/2, phosphatidylinositol 3-kinase (PI3K),
      protein kinase A (PKA) and endothelial Nitric Oxide synthase (eNOS) signaling.
      METHODS: In the present study, using the isolated and Langendorff-perfused rat
      heart as a model system we analyzed: i) whether and to which extent 17betaE2
      modifies mammalian ventricular myocardial relaxation (lusitropism); ii) the type
      of ERs and the signaling pathways involved in this effect. RESULTS: We found that
      17betaE2 negatively modulated the ventricular lusitropic performance. This
      effect, which partially involved the vascular endothelium, recruited ERbeta and
      occurred via PI3K, eNOS-NO-cGMP-protein kinase G (PKG) transduction cascade. Of
      note, 17betaE2-mediated negative lusitropism associated with a modification of
      phospholamban (PLN) phosphorylation and S-nitrosylation (SNO) both in isolated
      Langendorff rat heart and in isolated cardiomyocytes. CONCLUSION: Taken together,
      our results allow including 17betaE2 to the family of substances that control
      ventricular relaxation. This is of relevance in relation not only to the normal
      endocrine control of cardiac function, but also to physio-pathologic conditions
      characterized by an altered ventricular diastolic performance.

PMID- 21865848
TI  - Homocysteine induces phosphatidylserine exposure in cardiomyocytes through
      inhibition of Rho kinase and flippase activity.
AB  - AIMS: Increased levels of homocysteine (Hcy) form an independent risk factor for
      cardiovascular disease. In a previous study we have shown that Hcy induced
      phosphatidylserine (PS) exposure to the outer leaflet of the plasma membrane in
      cardiomyocytes, inducing a pro-inflammatory phenotype. In the present study the
      mechanism(s) involved in Hcy-induced PS exposure were analyzed. METHODS: H9c2 rat
      cardiomyoblasts were subjected to 2.5 mM D,L-Hcy and analyzed for RhoA
      translocation and activity, Rho Kinase (ROCK) activity and expression and
      flippase activity. In addition, the effect of ROCK inhibition with Y27632 on Hcy
      induced PS exposure and flippase activity was analyzed. Furthermore, GTP and ATP
      levels were determined. RESULTS: Incubation of H9c2 cells with 2.5 mM D,L-Hcy did
      not inhibit RhoA translocation to the plasma membrane. Neither did it inhibit
      activation of RhoA, even though GTP levels were significantly decreased. Hcy did
      significantly inhibit ROCK activation, but not its expression, and did inhibit
      flippase activity, in advance of a significant decrease in ATP levels. ROCK
      inhibition via Y27632 did not have significant added effects on this. CONCLUSION:
      Hcy induced PS exposure in the outer leaflet of the plasma membrane in
      cardiomyocytes via inhibition of ROCK and flippase activity. As such Hcy may
      induce cardiomyocytes vulnerable to inflammation in vivo in hyperhomocysteinaemia
      patients.

PMID- 21865849
TI  - Integration properties of Wharton's jelly-derived novel mesenchymal stem cells
      into ventricular slices of murine hearts.
AB  - Wharton's jelly (WJ) is a rich source of multiple-lineage differentiating cells,
      recently proposed for cell replacement therapy. However, their ability to
      integrate into the cardiac tissue has not been elucidated, yet. We employed in
      vitro cardiac transplantation models to investigate the capacity of a novel
      population of human WJ-derived mesenchymal stem cells (nMSCs) to integrate into
      both living and ischemic cardiac tissue. NMSCs were characterized for the
      expression of stem/progenitor cell genes and proteins, as well as for multi
      lineage differentiation potential. To assess their integration properties, nMSCs
      were cocultured with either living or ischemic embryonic murine ventricular
      slices. Immunohistochemical analyses were performed on cryosections of cocultured
      preparations to allow human cells tracking within the cocultures. Results showed
      that nMSCs shared MSC and endothelial colony-forming cell characteristics at
      gene, protein, and functional levels. NMSCs were markedly chemoattracted towards
      the ventricular slices, integrating robustly into the depth of both living and
      ischemic cardiac tissue. In conclusion, the functional ability of WJ-derived
      cells to populate the cardiac tissue could be validated in vitro. The
      transplantation models described could be further used to depict the mechanisms
      of WJ-derived cells integration into the cardiac tissue, contributing to
      optimization of reliable cell therapies for cardiac repair.

PMID- 21865850
TI  - Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a
      disturbed QRS complex.
AB  - BACKGROUND/AIMS: The aim of the study was to characterize the whole cell current
      of the two-pore domain potassium channel TASK-1 (K2P3) in mouse ventricular
      cardiomyocytes (I(TASK-1)) and to analyze the cardiac phenotype of the TASK-1(-/
      ) mice. METHODS AND RESULTS: We have quantified the ventricular I(TASK-1) current
      using the blocker A293 and TASK-1(-/-) mice. Surface electrocardiogram recordings
      of TASK-1(-/-) mice showed a prolonged QTc interval and a broadened QRS complex.
      The differences in electrocardiograms between wild type and TASK-1(-/-) mice
      disappeared during sympathetic stimulation of the animals. Quantitative RT-PCR,
      patch clamp recordings and measurements of hemodynamic performance of TASK-1(-/-)
      mice revealed no major compensatory changes in ion channel transcription. Action
      potential recordings of TASK-1(-/-) mouse cardiomyocytes indicated that I(TASK-1)
      modulates action potential duration. Our in vivo electrophysiological studies
      showed that isoflurane, which activates TASK-1, slowed heart rate and
      atrioventricular conduction of wild-type but not of TASK-1(-/-) mice. CONCLUSION:
      The results of an invasive electrophysiological catheter protocol in combination
      with the observed QRS time prolongation in the surface electrocardiogram point
      towards a regulatory role of TASK-1 in the cardiac conduction system.

PMID- 21865851
TI  - Activation of beta(3)-adrenoceptor promotes rapid pacing-induced atrial
      electrical remodeling in rabbits.
AB  - Cardiac electrophysiological function is under the regulatory control of the
      sympathetic nervous system. In addition to classical beta-adrenoceptors (beta-AR,
      including beta(1)- and beta(2)- subtypes), beta(3)-AR is also expressed in human
      heart and shows its distinctive functions. This study is aimed to elucidate the
      role of beta(3)-AR in the regulation of atrial fibrillation (AF), especially its
      role in rapid pacing-induced atrial electrical remodeling in rabbits. The rapid
      atrial pacing model was established by embedding electrodes in the right atrium
      pacing at a speed of 600 beats per minute. The protein level of beta(3)-AR in the
      atria was found significantly upregulated by western blot. The atrial effective
      refractory period (AERP) and its rate adaptation were decreased after pacing
      which were further shortened by BRL37344, a selective beta(3)-AR agonist, leading
      to the increase of AF inducibility and duration. Similarly, beta(3)-AR activation
      induced time-dependent shortening of action potential duration (APD), together
      with decrease of L-type calcium current (I(Ca,L)) and increase of inward
      rectifier potassium current (I(K1)) and transient outward potassium current
      (I(to)) in rapid pacing atrial myocytes. Meanwhile, all the effects were
      abolished by specific beta(3)-AR antagonist, SR59230A. In summary, our study
      represents that activation of beta(3)-AR promotes the atrial electrical
      remodeling process by altering the balance of ion channels in atrial myocytes,
      which provides new insights into the pharmacological role of beta(3)-AR in heart
      diseases.

PMID- 21865852
TI  - Potential therapeutic value of antioxidants for abnormal prolongation of QT
      interval and the associated arrhythmias in a rabbit model of diabetes.
AB  - Abnormal QT prolongation is the major cardiac electrical disorder and a predictor
      of mortality in diabetic patients. Our previous studies suggest that dysfunction
      of delayed rectifier K(+) current (I(Kr)) is the main cause for the problem. Here
      we report the potential therapeutic role and mechanisms of vitamin E in the
      rabbit model of diabetes. The QT interval and action potential duration were
      considerably prolonged with frequent occurrence of ventricular tachyarrhythmias
      in diabetic rabbits. Administration of vitamin E corrected the abnormal QT
      prolongation and abolished the arrhythmic incidence. I(Kr) was found markedly
      reduced resulting in slowing of cardiac repolarization thereby QT prolongation in
      diabetic hearts. The diabetic depression of I(Kr) is primarily ascribed to
      oxidative damages to the cardiac membrane and proteins, as indicated by the
      overproduction of reactive oxygen species leading to severe lipid peroxidation
      and protein oxidation. Moreover, I(Kr) depression is most likely due to the
      dysfunction of HERG K(+) channel, the major subunit underlying native I(Kr), in
      response to oxidative stress, for peroxide anion-generating system produced
      similar depression of HERG channels. Vitamin E restored the depressed I(Kr) and
      HERG by its antioxidant actions which likely underlie its beneficial effects on
      diabetic QT prolongation and the associated arrhythmias. The data indicate that
      an antioxidant is sufficient for reversing the I(Kr)/I(HERG) dysfunction and the
      consequent electrical disorders in diabetic hearts. Our study also conceptually
      simplifies the complex nature of diabetic electrical disorders to primarily
      oxidative stress, and should stimulate interest in antioxidants as a therapeutic
      strategy for diabetic QT prolongation.

PMID- 21865853
TI  - Ischemia induces closure of gap junctional channels and opening of hemichannels
      in heart-derived cells and tissue.
AB  - AIM: Gap junction intercellular communication (GJIC) and hemichannel permeability
      may have important roles during an ischemic insult. Our aim was to evaluate the
      effect of ischemia on gap junction channels and hemichannels. METHODS: We used
      neonatal rat heart myofibroblasts and simulated ischemia with a HEPES buffer with
      high potassium, low pH, absence of glucose, and oxygen tension was reduced by
      dithionite. Microinjection, western blot, immunofluorescence, cell viability and
      dye uptake were used to evaluate the effects induced by dithionite. Isolated
      perfused rat hearts were used to analyse infarct size. RESULTS: Short period with
      simulated ischemia reduced the ability to transfer a dye between neighbouring
      cells, which indicated reduced GJIC. Prolonged exposure to simulated ischemia
      caused opening of hemichannels, and cell death was apparent while gap junction
      channels remained closed. Connexin 43 became partially dephosphorylated and the
      total amount decreased during simulated ischemia. We were not able to detect the
      alternative hemichannel-forming protein, Pannexin 1, in these cells. The
      potential importance of Connexin 43 or Pannexin 1 hemichannels in ischemia
      induced infarct in the intact heart was studied by perfusion of the heart in the
      presence of peptides that block one or the other type of hemichannels. The
      connexin-derived peptide, Gap26, significantly reduced the infract/risk zone
      ratio (control 48.7+/-4.2% and Gap26 19.4+/-4.1%, p<0.001), while the pannexin
      derived peptide, (10)Panx1, did not change infarct/risk ratio. CONCLUSION:
      Connexin 43 is most likely responsible for both closure of gap junction channels
      and opening of hemichannels during simulated ischemia in neonatal rat heart
      myofibroblasts. Opening of connexin 43 hemichannels during ischemia-reperfusion
      seems to be an important mechanism for ischemia-reperfusion injury in the heart.
      By preventing the opening of these channels during early ischemia-reperfusion the
      infarct size becomes significantly reduced.

PMID- 21865854
TI  - NFKB is an unexpected major mediator of interleukin-15 signaling in cerebral
      endothelia.
AB  - Interleukin (IL)-15 and its receptors are induced by tumor necrosis factor alpha
      (TNF) in the cerebral endothelial cells composing the blood-brain barrier, but it
      is not yet clear how IL-15 modulates endothelial function. Contrary to the known
      induction of JAK/STAT3 signaling, here we found that nuclear factor (NF)- kappaB
      is mainly responsible for IL-15 actions on primary brain microvessel endothelial
      cells and cerebral endothelial cell lines. IL-15-induced transactivation of an
      NFkappaB luciferase reporter resulted in phosphorylation and degradation of the
      inhibitory subunit IkappaB that was followed by phosphorylation and nuclear
      translocation of the p65 subunit of NFkappaB. An IkappaB kinase inhibitor Bay 11
      7082 only partially inhibited IL-15-induced NFkappaB luciferase activity. The
      effect of IL-15 was mediated by its specific receptor IL-15Ralpha, since
      endothelia from IL-15Ralpha knockout mice showed delayed nuclear translocation of
      p65, whereas those from knockout mice lacking a co-receptor IL-2Rgamma did not
      show such changes. At the mRNA level, IL-15 and TNF showed similar effects in
      decreasing the tight junction protein claudin-2 and increasing the p65 subunit of
      NFkappaB but exerted different regulation on caveolin-1 and vimentin. Taken
      together, NFkappaB is a major signal transducer by which IL-15 affects cellular
      permeability, endocytosis, and intracellular trafficking at the level of the
      blood-brain barrier.

PMID- 21865856
TI  - EMD638683, a novel SGK inhibitor with antihypertensive potency.
AB  - The serum- and glucocorticoid-inducible kinase 1 (SGK1) is transcriptionally
      upregulated by mineralocorticoids and activated by insulin. The kinase enhances
      renal tubular Na(+)-reabsorption and accounts for blood pressure increase
      following high salt diet in mice made hyperinsulinemic by dietary fructose or
      fat. The present study describes the in vitro and in vivo efficacy of a novel
      SGK1 inhibitor (EMD638683). EMD638683 was tested in vitro by determination of
      SGK1-dependent phosphorylation of NDRG1 (N-Myc downstream-regulated gene 1) in
      human cervical carcinoma HeLa-cells. In vivo EMD638683 (4460 ppm in chow, i.e.
      approx. 600 mg/kg/day) was administered to mice drinking tap water or isotonic
      saline containing 10% fructose. Blood pressure was determined by the tail cuff
      method, and urinary electrolyte (flame photometry) concentrations determined in
      metabolic cages. In vitro testing disclosed EMD638683 as a SGK1 inhibitor with an
      IC50 of 3 MUM. Within 24 hours in vivo EMD638683 treatment significantly
      decreased blood pressure in fructose/saline-treated mice but not in control
      animals or in SGK1 knockout mice. EMD638683 failed to alter the blood pressure in
      SGK1 knockout mice. Following chronic (4 weeks) fructose/high salt treatment,
      additional EMD638683 treatment again decreased blood pressure. EMD638683 thus
      abrogates the salt sensitivity of blood pressure in hyperinsulinism without
      appreciably affecting blood pressure in the absence of hyperinsulinism. EMD638683
      tended to increase fluid intake and urinary excretion of Na(+), significantly
      increased urinary flow rate and significantly decreased body weight. CONCLUSION:
      EMD638683 could serve as a template for drugs counteracting hypertension in
      individuals with type II diabetes and metabolic syndrome.

PMID- 21865855
TI  - Oral carnosine supplementation prevents vascular damage in experimental diabetic
      retinopathy.
AB  - BACKGROUNDS/AIMS: Pericyte loss, vasoregression and neuroglial activation are
      characteristic changes in incipient diabetic retinopathy. In this study, the
      effect of the antioxidant and antiglycating dipeptide carnosine was studied on
      the development of experimental diabetic retinopathy. MATERIALS/METHODS: STZ
      induced diabetic Wistar rats were orally treated with carnosine (1g/kg body
      weight/day). Retinal vascular damage was assessed by quantitative morphometry.
      Retinal protein extracts were analyzed for markers of oxidative stress, AGE
      formation, activation of the hexosamine pathway and changes in the expression of
      Ang-2, VEGF and heat shock proteins Hsp27 and HO-1. Glial cell activation was
      analyzed using Western blot analysis and immunofluorescence of GFAP expression
      and retinal neuronal damage was histologically examined. RESULTS: Oral carnosine
      treatment prevented retinal vascular damage after 6 months of experimental
      hyperglycemia. The protection was not caused by ROS- or AGE-inhibition, but
      associated with a significant induction of Hsp27 in activated glial cells and
      normalization of increased Ang-2 levels in diabetic retinas. A significant
      reduction of photoreceptors in retinas of carnosine treated animals was noted.
      CONCLUSION: Oral carnosine treatment protects retinal capillary cells in
      experimental diabetic retinopathy, independent of its biochemical function. The
      vasoprotective effect of carnosine might be mediated by the induction of
      protective Hsp27 in activated glial cells and normalization of hyperglycemia
      induced Ang-2.

PMID- 21865857
TI  - Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation
      of Na(+)/K(+)/2Cl(-) cotransporter.
AB  - We have recently reported that Na(+)/K(+)/2Cl(-) cotransporter isoform 1 (NKCC1)
      plays an essential role in nerve growth factor (NGF)-induced neurite outgrowth in
      PC12D cells. On the other hand, it has been reported that dietary flavonoids,
      such as quercetin, apigenin, and luteolin, stimulate various ion transporters. In
      the present report, we investigated the effect of quercetin, a flavonoid, on NGF
      induced neurite outgrowth in PC12 cells (the parental strain of PC12D cells).
      Quercetin stimulated the NGF-induced neurite outgrowth in a dose-dependent
      manner. Knockdown of NKCC1 by RNAi methods abolished the stimulatory effect of
      flavonoid. Quercetin stimulated NKCC1 activity (measured as bumetanide-sensitive
      (86)Rb influx) without any increase in the expression level of NKCC1 protein. The
      stimulatory effect of quercetin on neurite outgrowth was dependent upon
      extracellular Cl(-). These observations indicate that quercetin stimulates the
      NGF-induced neurite outgrowth via an increase in Cl(-) incorporation into the
      intracellular space by activating NKCC1 in PC12 cell.

PMID- 21865858
TI  - DHA protects against zinc mediated alterations in neuronal cellular
      bioenergetics.
AB  - Zinc accumulation may impair cellular bioenergetics, which is associated with
      neuronal apoptosis. We simultaneously assessed anaerobic and aerobic metabolism
      in live cells to characterise this effect and hypothesised that the omega 3 fatty
      acid docosahexaenoic acid (DHA) would protect against any zinc mediated
      alterations in bioenergetics. In this study we observed a decrease in cellular
      oxygen consumption, but not glycolytic rate, following chronic zinc exposure,
      which was specific for neuronal cells. This was due to impaired ATP turnover,
      without any other effects on mitochondrial function, and was restored by DHA. DHA
      had no further effects on bioenergetics. These data suggest that zinc disrupts
      bioenergetics at a point distal to the respiratory chain, which is restored by
      DHA.

PMID- 21865859
TI  - Amoxapine inhibits delayed outward rectifier K(+) currents in cerebellar granule
      cells via dopamine receptor and protein kinase A activation.
AB  - BACKGROUND: Although tricyclic antidepressants amoxapine is proposed to target 5
      HT and D2 receptors, very few studies have addressed the effect of amoxapine on
      molecular and cellular mechanisms via receptor pathways. In this study, we test
      the effect of amoxapine on rat cerebellar granule neurons (CGNs) to address this
      possibility. METHODS: CGNs cell culture, whole-cell current recording using a
      patch-clamp technique, western blot and non-radioactive detection analysis of
      phosphorylated protein kinase A (PKA) were used. RESULTS: Amoxapine inhibits
      delayed rectifier potassium (I(K)) current in a dose-dependent manner and
      modulates inactivation properties in CGNs. Those effects were not eliminated by
      preincubation with 5-HT or 5-HT receptor antagonists, but abolished by dopamine
      and D1/D5 receptor antagonists. Application of GTPgamma-S and inhibitor of the Gs
      signalling cascade abolished the amoxapine-induced effect on I(K). The
      application of forskolin or dibutyryl-cAMP mimicked the inhibitory effect of
      amoxapine on I(K). Western blotting for phosphorylated PKA revealed that
      amoxapine significantly increased the intracellular levels of phosphorylated PKA,
      a marker of PKA activation. CONCLUSION: Amoxapine inhibits I(K) currents in rat
      CGNs via cAMP/PKA-dependent pathways, as in mouse cortical neurons we reported
      earlier, but that involves D1-like receptors instead of 5-HT receptors.

PMID- 21865860
TI  - Higher infiltration by Th17 cells compared with regulatory T cells is associated
      with severe acute T-cell-mediated graft rejection.
AB  - The aim of this study was to evaluate whether the Th17 and Treg cell infiltration
      into allograft tissue is associated with the severity of allograft dysfunction
      and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one
      allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens
      were immunostained for FOXP3 and IL-17. The allograft function was assessed at
      biopsy by measuring serum creatinine (Scr) concentration, and by applying the
      modified diet in renal disease (MDRD) formula, which provides the estimated
      glomerular filtration rate (eGFR). The severity of allograft tissue injury was
      assessed by calculating tissue injury scores using the Banff classification. The
      average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2
      and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/-
      8.2. The Treg/Th17 ratio was significantly associated with allograft function
      (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular
      injury (P < 0.05, all parameters). In separate analyses of the number of
      infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly
      associated with allograft function and the severity of tissue injury. By
      contrast, Treg cell infiltration was not significantly associated with allograft
      dysfunction or the severity of tissue injury. The results of this study show that
      higher infiltration of Th17 cell compared with Treg cell is significantly
      associated with the severity of allograft dysfunction and tissue injury.

PMID- 21865861
TI  - Improvement of plastid transformation efficiency in potato by using vectors with
      homologous flanking sequences.
AB  - Low transformation frequencies limit the use of plastid transformation in potato
      and other crops. Hence, a breakthrough in chloroplast genetic engineering of
      agronomically important species is a highly desirable goal. We succeeded in
      achieving potato transformation efficiency up to one shoot every bombardment
      using a modified regeneration procedure and novel vectors containing potato
      flanking sequences for transgene integration by homologous recombination in the
      Large Single Copy region of the plastome. Vector delivery was performed by the
      biolistic approach. Such efficiency corresponds to 15-18-fold improvement
      compared to previous results obtained in potato with a progenitor vector of that
      used in our study, and is comparable to that usually achieved with tobacco. The
      results obtained represent a significant advancement towards the implementation
      of the plastid transformation technology in potato breeding and biotechnology.

PMID- 21865862
TI  - TALE nucleases and next generation GM crops.
AB  - Site-specific and adaptable DNA binding domains are essential modules to develop
      genome engineering technologies for crop improvement. Transcription activator
      like effectors (TALEs) proteins are used to provide a highly specific and
      adaptable DNA binding modules. TALE chimeric nucleases (TALENs) were used to
      generate site-specific double strand breaks (DSBs) in vitro and in yeast,
      Caenorhabditis elegans, mammalian and plant cells. The genomic DSBs can be
      generated at predefined and user-selected loci and repaired by either the non
      homologous end joining (NHEJ) or homology dependent repair (HDR). Thus, TALENs
      can be used to achieve site-specific gene addition, stacking, deletion or
      inactivation. TALE-based genome engineering tools should be powerful to develop
      new agricultural biotechnology approaches for crop improvement. Here, we discuss
      the recent research and the potential applications of TALENs to accelerate the
      generation of genomic variants through targeted mutagenesis and to produce a non
      transgenic GM crops with the desired phenotype.

PMID- 21865863
TI  - Bt brinjal in India: a long way to go.
AB  - Brinjal occupies the major proportion amongst all vegetable crops in India and is
      vulnerable to many diseases caused by insect-pests, fungus, bacteria and virus.
      Brinjal production is extensively affected by the insect brinjal fruit and shoot
      borer. Use of conventional chemical pesticides not only damage environment
      including the biotic and abiotic components but, also affect human health. Bt
      Brinjal was developed to combat brinjal fruit and shoot borer that has an
      advantage minimizing use of chemical pesticides. Extensive biosafety
      investigations, nutritional studies, substantial equivalence studies, relative
      toxicity and allergenicity assessment using animal models like Sprague Dawley
      rats, Brown Norway rats, rabbit, fish, chicken, goats, etc. revealed no
      significant differences between genetically modified brinjal and its native
      counterpart. Bt brinjal could effectively control the target pest and was found
      to be safe for environment and human health. In spite of all the scientific
      studies, release of Bt Brinjal has been put under moratorium. Indian government
      has constituted an expert committee to address this issue. In this review we have
      tried to explore the facts related to Bt Brinjal including its production, use of
      Bt toxin, use of chemical pesticides in controlling the FSB in native brinjal,
      along with perspective of public opinion and government initiatives. Key words:
      Bt Brinjal, agriculture, insecticides, GM foods, agrobacterium, transgenic crops.

PMID- 21865864
TI  - Regeneration of Jatropha curcas through efficient somatic embryogenesis and
      suspension culture.
AB  - .Using immature zygotic embryos as explants, we have developed an efficient
      method for somatic embryogenesis in three germplasm accessions collected from
      China, India and Indonesia. Indirect somatic embryogenesis was achieved when
      endosperm tissue and immature embryos between 0.5-1.0 cm in length were cultured
      in a medium with 2,4-D, preferably at 5-10 mg/l, followed by a shift to a hormone
      free medium supplemented with glutamine and asparagine.  Production of secondary
      embryos was improved by supplementing KNO3, glutamine and asparagine. 2,4-D (0.1
      0.2 mg/l). PEG 8000 (5-10%) were essential for maintenance of embryogenic calli
      in liquid medium. Regeneration of soil-ready plants took as short as 3 months
      using the suspension cultures. Over 95% of the regenerated trees were able to
      flower and set seeds with no discernable morphological abnormality. This
      regeneration method is expected to facilitate the development of more efficient
      transformation system for Jatropha curcas.

PMID- 21865865
TI  - Amflora: great expectation for GM crops in Europe. Interview by Naglaa Abdallah.

PMID- 21865866
TI  - The first approved transgenic rice in China.

PMID- 21865867
TI  - Using genetic variability available in the breeder's pool to engineer fruit
      quality.
AB  - We substantiate here the opinion that experts in biotechnology and natural
      biodiversity can work together on the production of successive waves of next
      generation GM fruit crops to improve organoleptic and nutritional quality and
      therefore generate wider public acceptance. In this scenario genetic engineering
      becomes a faster and more precise way of transferring genes of interest to fruit
      crop plants from the same or sexually compatible species (intra- or cisgenesis)
      than more traditional methods, such as MASPB. The availability of complete genome
      sequences for an increasing number of crop plants, as well as the results from
      genomics studies, can assist in the identification of gene-to-trait association.
      The next wave of GM crops will be able to take full advantage of a Synthetic
      Biology-based strategy in the development of new fruit varieties by using DNA not
      necessarily present in the breeder's pool for a wide range of applications. There
      are still a number of challenges which require attention, such as identifying
      genes and allelic forms associated with traits of interest and improving the
      precision and stability of the transferred DNA.

PMID- 21865868
TI  - Engineering the plant genome: prospects of selection systems using non-antibiotic
      marker genes.
AB  - In the past two to three decades, great progress has been achieved in the field
      of plant genetic manipulation. This progress is based on fine-tuning gene
      transfer methods, selection of transformed cells and regulation of transgene
      expression. Transgenic plant production requires selectable marker genes that
      enable the selection of transformed cells, tissue and plants. The most used are
      those that exhibit resistance to antibiotics or herbicides. Although this type of
      selection is routinely practiced, there are perceived risks in the deployment of
      transgenic plants containing these markers. A number of strategies have emerged
      on the development of alternate selection systems referred to as positive
      selection and marker-free systems. Transgenes that permit plant cells to utilize
      new carbon sources are being employed in transformation research. Current
      research on development of novel selection methods in transgenics is growing
      rapidly and its application is being tested in different plant species.

PMID- 21865869
TI  - Genetically modified crops for biomass increase. Genes and strategies.
AB  - Genetically modified crops (GMCs) have been developed to accelerate the creation
      of new varieties with improved characteristics such as disease resistance, stress
      tolerance and higher quality composition. However, agriculture, without
      minimizing its role in food, feed and fiber source, has become important for the
      energy matrix of many countries. GMCs are also attractive systems that could
      fulfill the requirements for these new necessities. An increase of crop yields in
      an environmental friendly system is a new goal for plant biology research in the
      twenty-first century. In particular, biomass yield improvement is needed to
      render the use of biofuels economically feasible. In this context, research
      directed toward increasing biomass production has attracted much attention and a
      considerable effort is being made to reach new goals. Nonetheless, in some cases
      differentiated strategies are needed, as biomass improvement requires approaches
      other than those employed with traditional crops. This review summarizes the
      various approaches applied so far to modulate plant growth applying molecular
      biology-based strategies and increase biomass production, and it highlights
      several outstanding issues about the developmental constraints that must be
      addressed.

PMID- 21865870
TI  - Challenges.
AB  - Genetically modified plants have the same goal as conventional breeding:: to
      develop better varieties for farmers, the environment and consumers. "We have the
      capacity to eliminate hunger from the face of the earth in: our lifetime. We need
      only the will." John Kennedy, World Food Congress: in 1963. The will is all we
      need to concur hunger. This is our challenge: at GM crops, our challenge as
      scientists, and above all our challenge as: human being.

PMID- 21865871
TI  - Conducting public-sector research on commercialized transgenic seed: in search of
      a paradigm that works.
AB  - Public-sector scientists have a mandate to independently evaluate agricultural
      products available to American farmers on the open market, whereas the companies
      that sell the products must protect their intellectual property.  However, as a
      consequence of the latter concern, public scientists currently are prohibited by
      industry-imposed restrictions from conducting research on commercialized
      transgenic seed without permission of the company.  Industry acknowledged the
      seriousness of the problem after public warnings by a large group of
      entomologists to EPA and scientific advisory panels that the assumption of
      independence of public-sector studies on these products is no longer valid under
      current restrictions.  Both industry and public scientists are working to find an
      amicable, mutually-acceptable solution.  Recently, the American Seed Trade
      Association brokered a draft set of principles designed to protect the legitimate
      property rights of companies while allowing public scientists independence to
      conduct most types of research on their commercialized products without the need
      for case-by-case agreements.  While there are a number of potential pitfalls in
      implementation of the principles across companies, this effort represents a major
      step forward, and there is reason for optimism that this approach can be made to
      work to the benefit of industry, public scientists, and the American public.

PMID- 21865872
TI  - The tarnished gold standard for GM risk assessment.
AB  - The American public's assessment of the accuracy of news stories is now at its
      lowest level in more than two decades, and their views of media bias and
      independence now match previous lows, according to a September 2009 Pew Research
      Center survey.  Only 29% of Americans say that news organizations usually get the
      facts right, while 63% say that news stories often are inaccurate.  Although
      there are no similar survey data for "peer-reviewed journals" -- which submit
      articles to review by independent experts before they are accepted for
      publication and which have long been considered science's "gold standard" - it is
      not uncommon for articles that are egregiously, obviously flawed to find their
      way into prominent international scientific publications. If the articles have
      policy implications, misinformation is quickly and widely propagated; feeds the
      propagandizing of opportunistic, anti-technology activists, and can have dire
      consequences.

PMID- 21865873
TI  - Amino acids conferring herbicide resistance in tobacco acetohydroxyacid synthase.
AB  - Acetohydroxyacid synthase (AHAS) (EC 4.1.3.18) is a target of commercially
      available herbicides such as sulfonylurea, imidazolinone, and triazolopyrimidine.
      In plants and microorganisms, AHAS catalyzes the first common reaction in the
      biosynthesis pathways leading to leucine, isoleucine and valine. Intensive
      studies using different approaches - including site-directed mutagenesis,
      molecular modeling and structural analysis - on plant AHAS-s have contributed to
      the understanding of the herbicide-AHAS interaction. Knowledge of the critical
      roles of amino acid residues of plant AHAS in conferring herbicide resistance
      will enable the creation of new herbicide-tolerant AHAS which could be used to
      develop herbicide-resistant transgenic plants. Moreover, such information will
      also elucidate design strategies for more efficient herbicides that could also
      kill weeds resistant to previously used AHAS-inhibiting herbicides. In this
      review, we summarize the results of intensive searches for amino acid residues
      and their substitutions that confer herbicide resistance in tobacco AHAS.

PMID- 21865874
TI  - Is genetically modified crop the answer for the next green revolution?
AB  - Post-green revolution advances made in biotechnology paved the way of cultivating
      the high-yielding, stress and disease resistant genetically modified (GM)
      varieties of wheat, rice, maize cotton and several other crops. The recent rapid
      commercialization of the genetically modified crops in Asia, Americas and
      Australia indicates the potentiality of this new technology. GM crops give higher
      yields and are rich in nutritional values containing vitamins and minerals and
      can thus can help to alleviate hunger and malnutrition of the growing population
      in the under developed and developing countries. It could also be possible to
      develop more biotic and abiotic stress resistant genotypes in these crops where
      it was difficult to develop due to the unavailability of genes of resistance in
      the crossing germplasms. However, further research and investigations are needed
      to popularize the cultivation of these crops in different parts of the world.
      This review provides an insight of the impact of GM crops on contemporary
      agriculture across the past few decades, traces its' history across time,
      highlights new achievements and breakthroughs and discusses the future
      implication of this powerful technology in the coming few decades.

PMID- 21865875
TI  - Viroids and RNA silencing: mechanism, role in viroid pathogenicity and
      development of viroid-resistant plants.
AB  - Viroids are autonomously replicating, small single-stranded circular RNA
      pathogens that do not code for proteins and may cause diseases in infected,
      susceptible plants. They have the ability to induce both RNA-mediated
      transcriptional gene silencing (TGS) and post-transcriptional gene silencing
      (PTGS), or RNA silencing, in infected plants. Their induced RNA silencing has
      also been demonstrated in a wheat germ extract system. A possible role of RNA
      silencing in viroid pathogenicity and evolution has been discussed. It is
      suggested that RNA silencing can be employed to engineer plants for viroid
      resistance and attempts to produce these plants have been also discussed.

PMID- 21865876
TI  - Genetic transformation of mature embryos of bread (T. aestivum) and pasta (T.
      durum) wheat genotypes.
AB  - The objective of the present study is to develop an efficient protocol for
      regeneration of transgenic wheat plants using Agrobacterium- mediated
      transformation of mature embryos of hexaploid bread wheat (Triticum aestivum) and
      tetraploid pasta wheat (Triticum durum). The data indicated that embryogenic
      calli were formed within 7 days in the presence of 2 mgl-1 2,4-D. Adventitious
      shoots emerged from the embryonic calli in the presence of 2 mgl-1 BA. Shoot
      regeneration frequency varied between wheat cultivars according to their genetic
      background differences. Regeneration frequency was higher in the cultivar Gemmiza
      10 (95 %) compared with the other cultivars tested. Mature embryos derived callus
      of the cultivars Gemmiza 10 and Gemmiza 9 were co-cultivated with A. tumefaciens
      strain LBA4404 harboring a binary vector pBI-121 containing the neomycin
      phosphotransferase-II gene (npt-II). The resulted putative transgenic plantlets
      were able to grow on kanamycin containing medium. A successful integration of the
      transgene was confirmed by analyzing the T0 plantlets using Southern
      hybridization and PCR amplification. The gus gene expression can be detected only
      in the transgenic plants. The reported protocol is reproducible and can be used
      to regenerate transgenic wheat plants expressing the genes present in A.
      tumifaciens binary vectors.

PMID- 21865877
TI  - Gene flow from transgenic common beans expressing the bar gene.
AB  - Gene flow is a common phenomenon even in self-pollinated plant species. With the
      advent of genetically modified plants this subject has become of the utmost
      importance due to the need for controlling the spread of transgenes. This study
      was conducted to determine the occurrence and intensity of outcrossing in
      transgenic common beans. In order to evaluate the outcross rates, four
      experiments were conducted in Santo Antonio de Goias (GO, Brazil) and one in
      Londrina (PR, Brazil), using transgenic cultivars resistant to the herbicide
      glufosinate ammonium and their conventional counterparts as recipients of the
      transgene. Experiments with cv. Olathe Pinto and the transgenic line Olathe M1/4
      were conducted in a completely randomized design with ten replications for three
      years in one location, whereas the experiments with cv. Perola and the transgenic
      line Perola M1/4 were conducted at two locations for one year, with the
      transgenic cultivar surrounded on all sides by the conventional counterpart. The
      outcross occurred at a negligible rate of 0.00741% in cv. Perola, while none was
      observed (0.0%) in cv. Olathe Pinto. The frequency of gene flow was cultivar
      dependent and most of the observed outcross was within 2.5 m from the edge of the
      pollen source. Index terms: Phaseolus vulgaris, outcross, glufosinate ammonium.

PMID- 21865878
TI  - A genomic approach to nutritional, pharmacological and genetic issues of faba
      bean (Vicia faba): prospects for genetic modifications.
AB  - Cultivated faba bean (Vicia faba) is widely used as human food, especially in
      Europe, Northern Africa and China.  In view of its superior feeding value over
      field peas or other legumes, it is also widely used as animal feed for a variety
      of species.   V. faba also contains medically important components such as 3,4
      dihydroxyphenylalanine (levo-DOPA, L-DOPA), the principal treatment used for
      Parkinson's disease patients.  However, this species also contains several
      antinutritional components, including the pyrimidine glycosides vicine and
      convicine; phytates; and the sucrose galactosides including raffinose, stachyose
      and verbascose.  We have undertaken a genomic project to provide publicly
      available expressed sequence tag sequences (EST) prepared from early to mid
      developing embryo in an attempt to identify genes that are likely to be involved
      in the biosynthesis of L-DOPA and the vicine group of compounds.  As initial
      examples of the utility of this approach, we describe the complete sequence of
      fabatin, new defensins, type 4 metallothioneins and a variety of other key genes
      which were identified in this EST library. No candidate sequences corresponding
      to the biosynthesis of L-DOPA or the vicine group could be identified at this
      early stage of seed development.

PMID- 21865879
TI  - Universal protein vaccines against Neisseria meningitidis serogroup B,
      Streptococcus pneumoniae and influenza.
AB  - Traditional vaccines can only be really effective when the antigenic diversity or
      variability of the micro-organisms in the same bacterial species or viral family
      is no more than marginally different, and when protection is mainly dependent
      from antibody-mediated immunity. One solution is to identify the antigens common
      to all of the strains in a species or family that are significantly capable of
      eliciting inactivating antibodies. A number of attempts have recently been made
      to develop vaccines with conserved and highly immunogenic antigens made using
      various and sometimes highly innovative approaches. Although none of these
      vaccines has yet been licensed for human use, some have been widely studied in
      experimental animals and humans, and seem to increase the possibility of
      preventing previously uncovered or only partially covered infectious diseases.
      This review provides a detailed description of the most important new information
      concerning protein vaccines against influenza and meningococcal and pneumococcal
      diseases.

PMID- 21865880
TI  - Guidance for future HTA applications to vaccines: the HPV lesson.
AB  - The HTA is a multidisciplinary approach which is increasingly applied worldwide
      in order to support decision-makers in the introduction of health technologies.
      The application of HTA to vaccines is quite recent and linked to the increasing
      number of vaccines available or in development, especially to those intended to
      non pediatric immunization. In this article a description of the HTA approach
      used in the evaluation of the bivalent HPV vaccine in Italy is provided; moreover
      the reasons for keeping HTA process "alive" and identifying new or pending Public
      Health issues are discussed. In fact, the project raised questions and challenges
      about the standardization and sharing of HTA methods in Italy. Recently the need
      of updating the results is starting to be seen as urgent due to the evolution of
      scientific knowledge, the availability of the first results after technology
      introduction and the observed differences in vaccination strategies among Italian
      regions. Moreover in these last two years after the completion of the HTA project
      a number of new issues have risen in the Italian context as immunization rates,
      regional vaccination strategies, processes for vaccine selection and health
      economic issues.

PMID- 21865881
TI  - Cortical thinning in verbal, visual, and both memory-predominant mild cognitive
      impairment.
AB  - The amnestic form of mild cognitive impairment (aMCI) is likely a precursor of
      Alzheimer disease (AD). Both verbal and visual memory tests are used in the
      diagnosis of aMCI; however, it is unknown which type of test is superior at
      predicting the underlying pathologic changes associated with AD. In this study,
      we compared the topography of cortical thinning among 3 subtypes of patients with
      aMCI: 33 patients with predominant verbal memory impairment (verbal-aMCI), 35
      with predominant visual memory impairment (visual-aMCI), and 56 with both verbal
      and visual memory-predominant impairment (both-aMCI), and 143 patients with
      normal cognition. As a result, patients with verbal-aMCI showed cortical thinning
      in the left anterior and medial temporal regions compared with individuals with
      normal cognition, while those with visual-aMCI did not show significant cortical
      thinning. The cortical thinning areas of both-aMCI group overlapped those of
      verbal-aMCI but were more widespread involving the bilateral temporal regions.
      These findings suggest that the verbal-aMCI and both-aMCI are more likely to be a
      precursor of AD than visual-aMCI, and that both-aMCI may be more advanced subtype
      than verbal-aMCI on the spectrum from MCI to AD.

PMID- 21865882
TI  - Signaling of glial cell line-derived neurotrophic factor and its receptor
      GFRalpha1 induce Nurr1 and Pitx3 to promote survival of grafted midbrain-derived
      neural stem cells in a rat model of Parkinson disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRalpha1
      have been implicated in the survival of ventral midbrain dopaminergic (DA)
      neurons, but the molecular mechanisms bywhich GDNF generates DA neurons in
      grafted midbrain-derived neural stem cells (mNSCs) are not understood. Midbrain
      derived neural stem cells isolated from rat embryonic mesencephalon (embryonic
      day 12) were treated with GDNF or in combination with GFRalpha1 small interfering
      RNA. Reverse transcription-polymerase chain reaction, Western blot, and
      immunocytochemistry were used totest the expression of the orphan nuclear
      receptor Nurr1 and thetranscription factor Pitx3 and newborn tyrosine hydroxylase
      (TH)-positive cells. Treatment of mNSCs with GDNF increased mNSCs' sphere
      diameter, reduced expression of caspase 3, and increased expression of Bcl-2.
      Glial cell line-derived neurotrophic factor-treated mNSCs enhanced Nurr1 and
      Pitx3 expression and the fraction of TH-, TH/Pitx3-, and TH/Nurr1-positive cells
      in culture. Grafted GDNF-treated mNSCs significantly decreased apomorphine
      induced rotation behavior in 6-hydroxydopamine-lesioned rats. Glialcell line
      derived neurotrophic factor-treated mNSCs showed increased numbers of TH/Pitx3-
      and TH/Nurr1-postivie cells. The effect elicited by GDNF was inhibited by small
      interfering RNA-mediated knockdown of GFRalpha1. Our data demonstrate the
      contribution of GDNF to DA neuron development and may also elucidate pathogenetic
      mechanisms in Parkinson disease and contribute to the development of novel
      therapies for the disorder.

PMID- 21865883
TI  - Long-term intrathecal infusion of outer surface protein C from Borrelia
      burgdorferi causes axonal damage.
AB  - Lyme neuroborreliosis (LNB) is the most frequent tick-borne infectious disease of
      the central nervous system. In acute LNB and the rare chronic state of infection,
      patients can experience cognitive deficits such as attention and memory
      disturbances. During LNB, single compounds of Borrelia burgdorferi sensu lato are
      released into the subarachnoid space.To investigate the pathogenesis of
      neurologic dysfunction in LNB, we determined that the outer surface protein C
      (OspC), a major virulence factor of B. burgdorferi, stimulated mouse microglial
      cells in a dose-dependent manner to release nitric oxide (EC50 = 0.24 mg/L) in
      vitro. To mimic pathophysiologic conditions of long-term release of this
      bacterial component in vivo, we treated C57BL/6 mice with recombinant OspC from
      Borrelia garinii or buffer by intraventricular infusion and tested them for
      behavioral deficits. After 4weeks, brains were examined by routine histology and
      immunohistochemistry. Assessment of spatial learning and memory of treated mice
      during OspC exposure did not reveal significant differences from controls.
      Continuous exposure to intrathecal B. burgdorferi OspC led to activation of
      microglia and axonal damage without demonstrable cognitive impairment in
      experimental mice. These results suggest that long-term intrathecal exposure to
      OspC resulted in axonal damage that may underlie the neurologic manifestations in
      chronic LNB.

PMID- 21865885
TI  - Transplanted myoblasts can migrate several millimeters to fuse with damaged
      myofibers in nonhuman primate skeletal muscle.
AB  - A major restriction of the intramuscular transplantation of myoblasts is that the
      grafted cells fuse mostly with myofibers along the injection trajectories. This
      has been attributed to a "lack of migration ability" of the grafted myoblasts. It
      has been assumed that grafted myoblasts remain motionless in the sites of
      delivery and fuse only with myofibers with which they come into contact. In the
      present study, we analyzed this phenomenon in 17 cynomolgus monkeys. We found
      that intramuscularly injected myoblasts within 1 hour after their injection are
      mainly located in the perimysium and not distributed along the injection
      trajectories. This suggested that the grafted myoblasts later migrate from the
      perimysium to fuse with myofibers that are damaged by the injections. Therefore,
      we analyzed whether beta-galactosidase-labeled myoblasts injected subcutaneously
      over skeletal muscles migrate in needle-damaged and nondamaged muscle regions. We
      observed that grafted myoblasts migrated up to 1cm in depth from the muscle
      surface into the muscles, although they seemingly fused mainly with damaged
      myofibers. Our findings suggest that myoblast transplantation is not necessarily
      restricted bya "lack of migration ability" of the grafted cells but by the fact
      that myoblasts fuse with regenerating myofibers and not with undamaged myofibers.

PMID- 21865884
TI  - Matrix metalloproteinases and their tissue inhibitors in cuprizone-induced
      demyelination and remyelination of brain white and gray matter.
AB  - Apart from their involvement in the pathogenesis of demyelinating diseases such
      as multiple sclerosis, there is emerging evidence that matrix metalloproteinases
      (MMPs) also promote remyelination. We investigated region-specific expression
      patterns of 11 MMPs and 4 tissueinhibitors of metalloproteinases (TIMPs) in the
      cuprizone murine demyelination model. Messenger RNA (mRNA) was extracted at
      different time points of exposure to cuprizone from microdissected samples of
      corpus callosum, cortex, and ex vivo isolated microglia and analyzedusing
      quantitative reverse transcription-polymerase chain reaction.Matrix
      metalloproteinase 12 and TIMP-1 mRNA were significantly upregulated versus age
      matched controls in both areas during demyelination and remyelination. Matrix
      metalloproteinases 3, 11, and 14 mRNA were upregulated only in white matter
      during remyelination. Matrix metalloproteinase 24 mRNA was downregulated during
      both demyelination and remyelination. To identify potential cellular sources of
      the MMPs and TIMPs, we isolated microglia and detected high MMP-12and TIMP-2 mRNA
      upregulation at the peak of demyelination.By immunohistochemistry, MMP-3 protein
      was localized in astrocytes and MMP-12 was identified in microglia, astrocytes,
      and cells of oligodendrocyte lineage. These findings suggest that MMPs and TIMPs
      have roles in the regulation of demyelination and remyelination in thismodel.
      Moreover, differences in the expression levels of these genesbetween white and
      gray matter reveal region-specific molecularmechanisms.

PMID- 21865886
TI  - Immunoelectron microscopic and biochemical studies of caspase-cleaved tau in a
      mouse model of tauopathy.
AB  - Neurofibrillary tangles (NFTs) have been implicated in mediating neuronal death
      and disease progression in human tauopathies; however, mounting in vivo data
      suggest that NFTs may not be the primary initiators of neurotoxicity. Caspase
      activity has been implicated in processes associated with the development of
      tauopathy, but the position that caspase activation holds in neurodegenerative
      cascades remains uncertain. Using multiphoton real-time imaging microscopy, de
      Calignon et al recently demonstrated that caspase activation precedes and leads
      to tangle formation within 24 hours in the rTg4510 mouse model of tauopathy.
      Here, we used immunoelectron microscopy to determine whether caspase-cleaved tau
      was present in NFTs of rTg4510 mice. Using a caspase-cleaved tau-specific
      antibody (TauC3), we found very little immunogold labeling in NFTs in the brains
      of rTg4510 mice. By immunohistochemistry, the number of TauC3-positive neurons
      was far less than the numbers of neurons stained with the MC1 antibody, which
      recognizes abnormal conformations of tau. Biochemically, caspase-cleaved tau was
      barely detectable in fractions of rTg4510 mouse brain extracts. Our data suggest
      that caspase activation might be one of multiple routes through which NFT
      formation occurs, rather than an obligatory initiation step in pathologic tau
      production in rTg4510 mice.

PMID- 21865887
TI  - Accumulation of transactive response DNA binding protein 43 in mild cognitive
      impairment and Alzheimer disease.
AB  - Transactive response DNA binding protein 43 (TDP-43) plays a central role in the
      neuropathology of frontotemporal lobar degeneration and amyotrophic lateral
      sclerosis, but the relationship between TDP-43 abnormalities and Alzheimer
      disease (AD) remains unclear. To determine whether TDP-43 can serve as a
      neuropathologic marker of AD, we performed biochemical characterization and
      quantification of TDP-43 in homogenates from parietal neocortex of subjects with
      aclinical diagnosis of no cognitive impairment (NCI, n = 12), mild cognitive
      impairment (MCI, n = 12), or AD (n = 12). Immunoblots revealed increased
      detergent-insoluble TDP-43 in the cortex of 0, 3, and 6 of the 12 individuals
      with NCI, MCI, or AD, respectively. Detergent-insoluble TDP-43 was positively
      correlated with the accumulation of soluble Abeta42, amyloid plaques, and paired
      helical filamenttau. In contrast, phospho-TDP-43 was decreased in the cytosolic
      fraction and detergent-soluble membrane/nuclear fraction from AD patients and
      correlated with antemortem cognitive function.Immunofluorescence analysis
      confirmed that the frequencies of individuals with TDP-43 or phospho-TDP-43
      cytoplasmic inclusions were higher in AD than in NCI, with MCI at an intermediate
      level. These data indicate that abnormalities of TDP-43 occur in an important
      subset of MCI and AD patients and that they correlate with the clinical and
      neuropathologic features of AD.

PMID- 21865888
TI  - Decreased GABAA receptor binding in the medullary serotonergic system in the
      sudden infant death syndrome.
AB  - gamma-Aminobutyric acid (GABA) neurons in the medulla oblongata help regulate
      homeostasis, in part through interactions with the medullary serotonergic (5-HT)
      system. Previously, we reported abnormalities in multiple 5-HT markers in the
      medullary 5-HT system of infants dying from sudden infant death syndrome (SIDS),
      suggesting that 5-HT dysfunction is involved in its pathogenesis. Here, we tested
      the hypothesis that markers of GABAA receptors are decreased in the medullary 5
      HT system in SIDS cases compared with controls. Using tissue receptor
      autoradiography with the radioligand H-GABA, we found 25% to 52% reductions in
      GABAA receptor binding density in 7 of 10 key nuclei sampled of the medullary 5
      HT system in the SIDS cases (postconceptional age [PCA] = 51.7 +/- 8.3, n = 28)
      versus age-adjusted controls (PCA = 55.3 +/- 13.5, n = 8) (p <= 0.04). By Western
      blotting, there was 46.2% reduction in GABAAalpha3 subunit levels in the
      gigantocellularis (component of the medullary 5-HT system) of SIDS cases (PCA =
      53.9 +/- 8.4, n = 24) versus controls (PCA = 55.3 +/- 8.3, n = 8) (56.8% standard
      in SIDS cases vs 99.35% in controls; p = 0.026). These data suggest that
      medullary GABAA receptors are abnormal in SIDS infants and that SIDS is a complex
      disorder of a homeostatic network in the medulla that involves deficits of the
      GABAergic and 5-HT systems.

PMID- 21865890
TI  - Spillover effects of community uninsurance on working-age adults and seniors: an
      instrumental variables analysis.
AB  - BACKGROUND: : Previous research suggests, but does not definitively establish,
      that a high level of uninsurance in a community may negatively affect access to
      and quality of health care for insured persons. OBJECTIVE: : To assess the effect
      of the level of uninsurance in a community on access to and satisfaction with
      care-an important dimension of quality-among insured persons. RESEARCH DESIGN: :
      The 1996 to 2006 Medical Expenditure Panel Survey Household Component data linked
      to data from the Current Population Survey, Area Resource File, and the
      InterStudy Competitive Edge. Analyses include 86,928 insured adult respondents
      living in approximately 200 large metropolitan areas. MAIN OUTCOME MEASURES: :
      Measures of whether an individual had a usual source of care, had any
      delay/difficulty obtaining needed care, used office-based services, used
      prescription drug services, and used any medical services, and measures of
      satisfaction with care. RESULTS: : Among privately insured adults, a higher
      community uninsurance rate resulted in a lower probability of having a usual
      source of care, having an office-based visit, having any medical expenditures,
      and reporting being satisfied with the quality of care provided by the usual
      source of care. A higher community uninsurance rate also led to a higher
      probability of reporting difficulty obtaining needed care. Among Medicare
      enrollees, a higher community uninsurance rate resulted in lower reported
      satisfaction with care and higher probability of experiencing difficulty or delay
      in getting needed care. CONCLUSIONS: : Our results suggest substantial spillover
      effects of the community uninsurance rate on access to and satisfaction with
      health care among insured working-age adults and seniors. Consequently, new
      efforts to address the problem of the uninsured may bring significant benefits to
      persons who already have insurance.

PMID- 21865889
TI  - Microtubule-severing ATPase spastin in glioblastoma: increased expression in
      human glioblastoma cell lines and inverse roles in cell motility and
      proliferation.
AB  - We studied the expression and distribution of the microtubule-severing enzyme
      spastin in 3 human glioblastoma cell lines (U87MG, U138MG, and T98G) and in
      clinical tissue samples representative of all grades of diffuse astrocytic
      gliomas (n = 45). In adult human brains, spastin was distributed predominantly in
      neuronsand neuropil puncta and, to a lesser extent, in glia. Compared with normal
      mature brain tissues, spastin expression and cellular distribution were increased
      in neoplastic glial phenotypes, especiallyin glioblastoma (p < 0.05 vs low-grade
      diffuse astrocytomas). Overlapping punctate and diffuse patterns of localization
      wereidentified in tumor cells in tissues and in interphase and mitotic cells
      ofglioblastoma cell lines. There was enrichment of spastin in the leading edges
      of cells in T98G glioblastoma cell cultures and in neoplastic cell populations in
      tumor specimens. Real-time polymerase chain reaction and immunoblotting
      experiments revealed greater levels of spastin messenger RNA and protein
      expression in theglioblastoma cell lines versus normal human astrocytes.
      Functional experiments indicated that spastin depletion resulted in reduced cell
      motility and higher cell proliferation of T98G cells. Toour knowledge, this is
      the first report of spastin involvement incellmotility. Collectively, our results
      indicate that spastinexpression in glioblastomas might be linked to tumor cell
      motility, migration, and invasion.

PMID- 21865891
TI  - On physician advocacy.

PMID- 21865892
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865893
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865894
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865895
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865896
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865897
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865898
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865899
TI  - Do medical professionalism and medical education involve commitments to political
      advocacy?

PMID- 21865901
TI  - Commentary: defining disability in health care education.
AB  - According to the 2008 American Community Survey, about 12% of the population of
      the United States is living with one or more disabling conditions. These
      conditions impact lives in a variety of ways, some with more or less direct
      impact on an individual's health and access to health care services. Although it
      has been 20 years since the passage of the Americans with Disabilities Act,
      people with disabilities still experience health disparities and a lack of access
      to the appropriate care. This commentary is part of a collection of articles that
      describe various aspects of incorporating content into the medical school
      curriculum to enhance the preparation of today's medical students to meet the
      needs of people with disabilities. The authors briefly describe the scope of the
      problem and define the population of people with disabilities that constitutes
      the focus of the work described in the other articles in this collection.

PMID- 21865902
TI  - Commentary: beyond educational initiatives: how can we change health care to
      improve the health of persons with disabilities?
AB  - Minihan and colleagues discuss necessary elements of an educational program to
      instruct generalist physicians in the care of individuals with disabilities. To
      support these physicians adequately in practice will require significant
      adaptations of health care financing, recognition of the unique medical needs of
      persons with disabilities, and efficient utilization of experienced clinical
      resources. The author outlines what remains to be addressed in the pursuit of
      better health for patients with disabilities as the U.S. health care system
      evolves.

PMID- 21865903
TI  - Commentary: physician-scientist attrition: stemming the tide through national
      networks for training and development.
AB  - Future advances in medicine depend on a reliable pipeline of physician
      scientists. However, the changing demographics of physician-scientists, including
      the advanced age of new MD investigators, and attrition along the physician
      scientist developmental pathway are cause for concern. Recently developed
      National Institutes of Health-funded national networks for physician-scientist
      training and development-such as the Advanced Research Institute in Geriatric
      Mental Health and the Pediatric Scientist Development Program-offer valuable
      approaches to supporting and retaining these trainees.

PMID- 21865904
TI  - Commentary: measurement and interpretation challenges in comparing student
      performance outcomes from different medical schools.
AB  - This commentary points to several measurement issues that arise in assessing
      medical student performance outcomes and then discusses the challenge of
      interpreting between-school differences. A problem often encountered in assessing
      student learning is creating an instrument that is at the right "pay grade." If
      it is too easy, ceiling effects compress scores. If it is too difficult, examinee
      performance can compress about chance values, and morale problems can occur.
      These issues are discussed in the context of a report by Williams and colleagues
      that measures medical student performance across five institutions on instruments
      assessing diagnostic pattern recognition and clinical data interpretation. The
      author of this commentary observes that, when interpreting between-school
      differences in assessing student learning, what can seem like small differences
      can have important consequences.

PMID- 21865905
TI  - Commentary: health care reform and the finances of academic medical centers.
AB  - Academic medical centers (AMCs; i.e., teaching hospitals) play a vital role in
      the U.S. health care system by pursuing a four-part, synergistic mission of
      clinical care, research, education, and community health. Historically, AMCs have
      used margins from clinical care to subsidize the cost of the other three
      missions. As a result, the clinical cost structure of AMCs is higher than other
      hospitals. The study by McCue and Thompson in this issue of Academic Medicine
      identifies certain factors (such as Medicaid payer mix) that are associated with
      the financial success of AMCs. For national health care reform to be successful
      and for health care to be affordable, all providers across the United States,
      including AMCs, must aggressively identify and implement opportunities to make
      care better and more efficient. Policies that shape national health care reform
      must account for AMCs' higher cost structures. If policy makers ignore these
      higher cost structures, the ability of AMCs to provide highly specialized
      services, to care for vulnerable populations, to advance knowledge through
      biomedical research, to educate the next generation of health professionals, and
      to improve community health will be at risk.

PMID- 21865907
TI  - Learning to be helpful.

PMID- 21865908
TI  - Medicine and the arts. Commentary.

PMID- 21865909
TI  - AM Last Page. How does the American Board of Medical Specialties advance quality
      health care in the United States?

PMID- 21865910
TI  - Disaster preparedness 10 years after 9/11.

PMID- 21865911
TI  - The case for specialized transport teams.

PMID- 21865912
TI  - Protecting ourselves and our patients.

PMID- 21865913
TI  - Protecting ourselves and our patients.

PMID- 21865916
TI  - Finding solutions to advance rural health.

PMID- 21865917
TI  - HPV vaccine reduces cervical abnormalities in teens.

PMID- 21865918
TI  - New drug for metastatic melanoma increases survival rate.

PMID- 21865921
TI  - More data: transitional care reduces readmissions.

PMID- 21865923
TI  - Transforming pain care: an IOM report.

PMID- 21865924
TI  - 9/11 and nursing, 10 years on.

PMID- 21865931
TI  - Care of the suicidal pediatric patient in the ED: a case study.
AB  - OVERVIEW: The suicide rate among children and adolescents has increased worldwide
      over the past few decades, and many who attempt suicide are first seen at EDs. At
      Childrens Hospital Boston (CHB), an algorithm-the Risk of Suicidality Clinical
      Practice Algorithm-has been developed to ensure evidence-based care supported by
      best practice guidelines. The authors of this article provide an overview of
      pediatric suicide and suicide attempts; describe screening, assessment, and
      interventions used at CHB; and discuss the nursing implications. An illustrative
      case study is also provided. KEYWORDS: algorithm, Asperger's syndrome, attempted
      suicide, bullying, emergency, emergency department, patient safety, pediatrics,
      pediatric suicide, suicide, suicide screening, triage.

PMID- 21865933
TI  - Cultivating quality: creating a unit-based resource nurse program.

PMID- 21865934
TI  - Evidence-based practice, step by step: sustaining evidence-based practice through
      organizational policies and an innovative model.
AB  - The team adopts the Advancing Research and Clinical Practice Through Close
      Collaboration model.This is the 12th and last article in a series from the
      Arizona State University College of Nursing and Health Innovation's Center for
      the Advancement of Evidence-Based Practice. Evidence-based practice (EBP) is a
      problem-solving approach to the delivery of health care that integrates the best
      evidence from studies and patient care data with clinician expertise and patient
      preferences and values. When it's delivered in a context of caring and in a
      supportive organizational culture, the highest quality of care and best patient
      outcomes can be achieved. The complete EBP series is available as a collection on
      our Web site; go to www.ajnonline.com and click on Collections.

PMID- 21865939
TI  - iNurse: patient privacy and company policy in online life.

PMID- 21865940
TI  - What one thing will make today better for you?

PMID- 21865941
TI  - Preserving surgical academia in the centenary of the Flexnerian Academic Health
      Center.

PMID- 21865942
TI  - First report from the American College of Surgeons Bariatric Surgery Center
      Network: laparoscopic sleeve gastrectomy has morbidity and effectiveness
      positioned between the band and the bypass.
AB  - OBJECTIVE: To assess the safety and effectiveness of the laparoscopic sleeve
      gastrectomy (LSG) as compared to the laparoscopic adjustable gastric band (LAGB),
      the laparoscopic Roux-en-Y gastric bypass (LRYGB) and the open Roux-en-Y gastric
      bypass (ORYGB) for the treatment of obesity and obesity-related diseases.
      BACKGROUND: LSG is a newer procedure being done with increasing frequency.
      However, limited data are currently available comparing LSG to the other
      established procedures. We present the first prospective, multiinstitutional,
      nationwide, clinically rich, bariatric-specific data comparing sleeve gastrectomy
      to the adjustable gastric band, and the gastric bypass. METHODS: This is the
      initial report analyzing data from the American College of Surgeons-Bariatric
      Surgery Center Network accreditation program, and its prospective, longitudinal,
      data collection system based on standardized definitions and collected by trained
      data reviewers. Univariate and multivariate analyses compare 30-day, 6-month, and
      1-year outcomes including morbidity and mortality, readmissions, and reoperations
      as well as reduction in body mass index (BMI) and weight-related comorbidities.
      RESULTS: One hundred nine hospitals submitted data for 28,616 patients, from
      July, 2007 to September, 2010. The LSG has higher risk-adjusted morbidity,
      readmission and reoperation/intervention rates compared to the LAGB, but lower
      reoperation/intervention rates compared to the LRYGB and ORYGB. There were no
      differences in mortality. Reduction in BMI and most of the weight-related
      comorbidities after the LSG also lies between those of the LAGB and the
      LRYGB/ORYGB. CONCLUSION: LSG has morbidity and effectiveness positioned between
      the LAGB and the LRYGB/ORYGB for data up to 1 year. As obesity is a lifelong
      disease, longer term comparative effectiveness data are most critical, and are
      yet to be determined.

PMID- 21865943
TI  - Diverting loop ileostomy and colonic lavage: an alternative to total abdominal
      colectomy for the treatment of severe, complicated Clostridium difficile
      associated disease.
AB  - OBJECTIVE: To determine whether a minimally invasive, colon-preserving approach
      could serve as an alternative to total colectomy in the treatment of severe,
      complicated Clostridium difficile-associated disease (CDAD). BACKGROUND: C.
      difficile is a significant cause of morbidity and mortality worldwide. Most cases
      will respond to antibiotic therapy, but 3% to 10% of patients progress to a
      severe, complicated, or "fulminant" state of life-threatening systemic toxicity.
      Although the advocated surgical treatment of total abdominal colectomy with end
      ileostomy improves survival in severe, complicated CDAD, outcomes remain poor
      with associated mortality rates ranging from 35% to 80%. METHODS: All patients
      who were diagnosed with severe, complicated ("fulminant") CDAD and were treated
      at the University of Pittsburgh Medical Center or VA Pittsburgh Healthcare System
      between June 2009 and January 2011 were treated with this novel approach. The
      surgical approach involved creation of a loop ileostomy, intraoperative colonic
      lavage with warmed polyethylene glycol 3350/electrolyte solution via the
      ileostomy and postoperative antegrade instillation of vancomycin flushes via the
      ileostomy. The primary end point for the study was resolution of CDAD. The
      matching number of patients treated with colectomy for CDAD preceding the
      initiation of this current treatment strategy was analyzed for historical
      comparison. RESULTS: Forty-two patients were treated during this time period.
      There was no significant difference in age, sex, pharmacologic immunosuppression,
      and Acute Physiology and Chronic Health Evaluation-II scores between our current
      cohort and historical controls. The operation was accomplished laparoscopically
      in 35 patients (83%). This treatment strategy resulted in reduced mortality
      compared to our historical population (19% vs 50%; odds ratio, 0.24; P = 0.006).
      Preservation of the colon was achieved in 39 of 42 patients (93%). CONCLUSIONS:
      Loop ileostomy and colonic lavage are an alternative to colectomy in the
      treatment of severe, complicated CDAD resulting in reduced morbidity and
      preservation of the colon.

PMID- 21865944
TI  - Effects of aggressive versus moderate glycemic control on clinical outcomes in
      diabetic coronary artery bypass graft patients.
AB  - OBJECTIVE: This study sought to determine whether aggressive glycemic control (90
      120 mg/dL) would result in more optimal clinical outcomes and less morbidity than
      moderate glycemic control (120-180 mg/dL) in diabetic patients undergoing
      coronary artery bypass graft (CABG) surgery. SUMMARY OF BACKGROUND DATA:
      Maintaining serum glucose levels between 120 and 180 mg/dL with continuous
      insulin infusions decreases morbidity in diabetic patients undergoing CABG
      surgery. Studies in surgical patients requiring prolonged ventilation suggest
      that aggressive glycemic control (<120 mg/dL) may improve survival; however, its
      effect in diabetic CABG patients is unknown. METHODS: Eighty-two diabetic
      patients undergoing CABG were prospectively randomized to aggressive glycemic
      control (90-120 mg/dL) or moderate glycemic control (120-180 mg/dL) using
      continuous intravenous insulin solutions (100 units regular insulin in 100 mL:
      normal saline) beginning at the induction of anesthesia and continuing for 18
      hours after CABG. Primary end points were the incidence of major adverse events
      (major adverse events = 30-day mortality, myocardial infarction, neurologic
      events, deep sternal infections, and atrial fibrillation), the level of serum
      glucose, and the incidence of hypoglycemic events. RESULTS: There were no
      differences in the incidence of major adverse events between the groups (17
      moderate vs 15 aggressive; P = 0.91). Patients with aggressive control had a
      lower mean glucose at the end of 18 hours of insulin infusion (135 +/- 12 mg/dL
      moderate vs 103 +/- 17 mg/dL aggressive; P < 0.0001). Patients with aggressive
      control had a higher incidence of hypoglycemic events (4 vs 30; P < 0.0001).
      CONCLUSIONS: In diabetic patients undergoing CABG surgery, aggressive glycemic
      control increases the incidence of hypoglycemic events and does not result in any
      significant improvement in clinical outcomes that can be achieved with moderate
      control. Clinical Trials.gov (ID #NCT00460499).

PMID- 21865945
TI  - Five hundred patients with Merkel cell carcinoma evaluated at a single
      institution.
AB  - OBJECTIVE: To identify factors associated with survival in Merkel cell carcinoma
      (MCC). BACKGROUND: Merkel cell carcinoma is a rare cutaneous neoplasm. Staging
      and treatment are based on studies, which incompletely characterize the disease.
      METHODS: Review of a prospective database was performed. Overall survival (OS)
      was estimated by the Kaplan-Meier method. Disease-specific death (DSD) was
      analyzed by the competing risks method. Factors associated with OS and DSD were
      determined by the log-rank test and Gray's test, respectively. RESULTS: A total
      of 500 patients with MCC treated at our institution from 1969 to 2010 were
      identified. Eighty-eight patients presented older than 6 months after diagnosis
      and were excluded from further analysis. Of the remaining 412 patients, the
      median age at diagnosis was 71 years. Median follow-up was 3 years. Fifty percent
      of patients died during follow-up: 25% died of disease, 24% died of other causes.
      Five-year OS and DSD were 56% and 30%, respectively. Pathologic stage and
      lymphovascular invasion were independent predictors of DSD. Patients with
      metastatic disease (stage 4) or clinically positive lymph nodes (stage 3b) had
      increased DSD compared with patients with microscopically positive (stage 3a) or
      negative lymph nodes (stage 1 and 2). There was no difference in DSD between
      stage 3a or 2 compared with stage 1. Importantly, only 1 of 132 patients without
      lymphovascular invasion died of MCC. CONCLUSIONS: OS is a poor measure of the
      influence of MCC on life expectancy. The presence of lymphovascular invasion and
      clinically, but not microscopically, positive lymph nodes were associated with
      increased DSD. These factors should be incorporated into MCC staging and
      treatment recommendations.

PMID- 21865947
TI  - Simulation-based mastery learning improves patient outcomes in laparoscopic
      inguinal hernia repair: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate a mastery learning, simulation-based curriculum for
      laparoscopic, totally extraperitoneal (TEP) inguinal hernia repair. BACKGROUND:
      Clinically relevant benefits from improvements in operative performance, time,
      and errors after simulation-based training are not clearly established. METHODS:
      After performing a baseline TEP in the OR, general surgery residents randomized
      to mastery learning (ML) or standard practice (SP) were reassessed during
      subsequent TEPs. The ML curriculum involved Web-based modules followed by
      training on a TEP simulator until expert performance was achieved. Operative
      time, performance, and patient outcomes adjusted for staff, resident
      participation, difficulty of repair, PGY-level, and patient comorbidities were
      compared between groups with mixed effects-ANOVA and generalized linear models.
      RESULTS: Fifty residents (PGY1-5) performed 219 TEP repairs on 146 patients.
      Baseline operative time, performance, and demographics were similar between
      groups. To achieve mastery, ML-residents (n = 26) required a median of 16 (range
      7-27) simulated repairs. After training, TEPs performed by ML-residents were
      faster than those by SP-residents, with time corrected for participation (mean +/
      SD, 34 +/- 8 minutes vs. 48 +/- 14 minutes; difference -13; 95%CI, -18 to -8; P
      < 0.001). Operative performance scores (GOALS, scale 6-30) were better for ML
      residents (21.9 +/- 2.8 vs. 18.3 +/- 3.8; P = 0.001). Intraoperative
      complications (peritoneal tear, procedure conversion), postoperative
      complications (urinary retention, seroma), and need for overnight stay were less
      likely in the ML group (adjusted odds ratios 0.14, 0.04, and 0, respectively; all
      P < 0.05). CONCLUSIONS: A simulation-based ML curriculum decreased operative
      time, improved trainee performance, and decreased intra- and postoperative
      complications and overnight stays after laparoscopic TEP inguinal hernia repair.
      ClinicalTrials.gov Identifier: NCT01085500.

PMID- 21865946
TI  - Identification of a biomarker profile associated with resistance to neoadjuvant
      chemoradiation therapy in rectal cancer.
AB  - OBJECTIVE: To identify a biomarker profile associated with tumor response to
      chemoradiation (CRT) in locally advanced rectal cancer. BACKGROUND: Rectal cancer
      response to neoadjuvant CRT is variable. Whereas some patients have a minimal
      response, others achieve a pathologic complete response (pCR) and have no viable
      cancer cells in their surgical specimens. Identifying biomarkers of response will
      help select patients more likely to benefit from CRT. METHODS: This study
      includes 132 patients with locally advanced rectal cancer treated with
      neoadjuvant CRT followed by surgery. Tumor DNA from pretreatment tumor biopsies
      and control DNA from paired normal surgical specimens was screened for mutations
      and polymorphisms in 23 genes. Genetic biomarkers were correlated with tumor
      response to CRT (pCR vs non-pCR), and the association of single or combined
      biomarkers with tumor response was determined. RESULTS: Thirty-three of 132 (25%)
      patients achieved a pCR and 99 (75%) patients had non-pCR. Three individual
      markers were associated with non-pCR; v-Ki-ras2 Kirsten rat sarcoma viral
      oncogene homolog mutation (P = 0.0145), cyclin D1 G870A (AA) polymorphism (P =
      0.0138), and methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT)
      polymorphism (P = 0.0120). Analysis of biomarker combinations revealed that none
      of the 27 patients with both tumor protein p53 (p53) and v-Ki-ras2 Kirsten rat
      sarcoma viral oncogene homolog mutations had a pCR. Further, in patients with
      both p53 and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations or
      the cyclin D1 G870A (AA) polymorphism or the methylenetetrahydrofolate reductase
      (NAD(P)H) C677T (TT) polymorphism (n = 52) the association with non-pCR was
      further strengthened; 51 of 52 (98%) of patients were non-pCR. These biomarker
      combinations had a validity of more than 70% and a positive predictive value of
      97% to 100%, predicting that patients harboring these mutation/polymorphism
      profiles will not achieve a pCR. CONCLUSIONS: A specific biomarker profile is
      strongly associated with non-pCR to CRT and could be used to select optimal
      oncologic therapy in rectal cancer patients. ClinicalTrials.org Identifier:
      NCT00335816.

PMID- 21865948
TI  - Coating human pancreatic islets with CD4(+)CD25(high)CD127(-) regulatory T cells
      as a novel approach for the local immunoprotection.
AB  - OBJECTIVES: To develop a novel approach for local immunoprotection using
      CD4(+)CD25(high)CD127(-) T regulatory cells (Tregs) attached to the surface of
      the islets before transplantation. BACKGROUND: Tregs expanded ex vivo can control
      allo and autoreactivity, therefore, Treg-based therapy may offer more effective
      protection for transplanted islets from immunologic attack than currently used
      immunosuppression. Local application of Tregs can make such therapy more
      clinically feasible and efficient. METHODS: Human islets were isolated and coated
      with allogeneic ex vivo expanded Tregs using biotin-poly(ethylene glycol)-N
      hydroxysuccinimide ester (biotin-PEG-NHS) and streptavidin as binding molecules.
      RESULTS: Coating pancreatic islets with Tregs did not affect islet viability
      (>90% fluorescein diacetate/propidium iodide) or the insulin secretion profile in
      dynamic islet perifusion assays. After in vitro incubation with allogeneic T
      effector cells, Treg-coated islets revealed preserved function with higher
      insulin secretion compared with controls-native islets, coated islets with T
      effector cells or when Tregs were added to the culture, but not attached to
      islets (P < 0.05). In addition, the Enzyme-linked immunosorbent spot (ELISPOT)
      assay revealed suppression of interferon (IFN)-gamma secretion, when T effector
      cells were challenged with Treg-coated islets comparing to controls (99 +/- 7 vs
      151 +/- 8 dots, respectively; P < 0.01). CONCLUSIONS: We demonstrated, for the
      first time, the ability to bind immune regulatory cells to target cells with
      preservation of their viability and function and protective activity against
      immune attack. If successfully tested in an animal model, local delivery of
      immunoprotective Tregs on the surface of transplanted pancreatic islets may be an
      alternative or improvement to the currently used immunosuppression.

PMID- 21865949
TI  - General surgery workloads and practice patterns in the United States, 2007 to
      2009: a 10-year update from the American Board of Surgery.
AB  - OBJECTIVE: To assess changes in general surgery workloads and practice patterns
      in the past decade. BACKGROUND: Nearly 80% of graduating general surgery
      residents pursue additional training in a surgical subspecialty. This has
      resulted in a shortage of general surgeons, especially in rural areas. The
      purpose of this study is to characterize the workloads and practice patterns of
      general surgeons versus certified surgical subspecialists and to compare these
      data with those from a previous decade. METHODS: The surgical operative logs of
      4968 individuals recertifying in surgery 2007 to 2009 were reviewed. Data from
      3362 (68%) certified only in Surgery (GS) were compared with 1606 (32%) with
      additional American Board of Medical Specialties certificates (GS+). Data from GS
      surgeons were also compared with data from GS surgeons recertifying 1995 to 1997.
      Independent variables were compared using factorial ANOVA. RESULTS: GS surgeons
      performed a mean of 533 +/- 365 procedures annually. Women GS performed far more
      breast operations and fewer abdomen, alimentary tract and laparoscopic procedures
      compared to men GS (P < 0.001). GS surgeons recertifying at 10 years performed
      more abdominal, alimentary tract and laparoscopic procedures compared to those
      recertifying at 20 or 30 years (P < 0.001). Rural GS surgeons performed far more
      endoscopic procedures and fewer abdominal, alimentary tract, and laparoscopic
      procedures than urban counterparts (P < 0.001). The United States medical school
      graduates had similar workloads and distribution of operations to international
      medical graduates. Compared to 1995 to 1997, GS surgeons from 2007 to 2009
      performed more procedures, especially endoscopic and laparoscopic. GS+ surgeons
      performed 15% to 33% of all general surgery procedures. CONCLUSIONS: GS practice
      patterns are heterogeneous; gender, age, and practice setting significantly
      affect operative caseloads. A substantial portion of general surgery procedures
      currently are performed by GS+ surgeons, whereas GS surgeons continue to perform
      considerable numbers of specialty operations. Reduced general surgery operative
      experience in GS+ residencies may negatively impact access to general surgical
      care. Similarly, narrowing GS residency operative experience may impair specialty
      operation access.

PMID- 21865951
TI  - Physical deformity as sequela of chronic catatonia and response to
      electroconvulsive therapy: a case report.
AB  - Chronic catatonia with posturing can cause joint contractures leading to greater
      morbidity associated with the physical deformity. We report a case of a young man
      with chronic catatonic schizophrenia with posturing of bilateral upper limbs in
      flexion leading to fixed flexion contracture of left metacarpophalangeal joints.
      Initiation of electroconvulsive therapy along with physical rehabilitation
      measures helped him regain full range of motion in the right upper limb. The
      fixed flexion contracture, however, remained resistant to intensive treatment
      efforts. Early interventions in the form of electroconvulsive therapy and
      physical rehabilitation can be useful in reversing such potentially disabling
      complications.

PMID- 21865950
TI  - Is surgical resection superior to transplantation in the treatment of
      hepatocellular carcinoma?
AB  - OBJECTIVE: To compare outcomes for patients with hepatocellular carcinoma (HCC)
      treated with either liver resection or transplantation. METHODS: A retrospective,
      single-institution analysis of 413 HCC patients from 1999 to 2009. RESULTS: A
      total of 413 patients with HCC underwent surgical resection (n = 106) and
      transplantation (n = 270) or were listed without receiving transplantation (n =
      37). Excluding transplanted patients with incidental tumors (n = 50), 257
      patients with suspected HCC were listed with the intent to transplant (ITT). The
      median diameter of the largest tumor by radiography was 6.0 cm in resected, 3.0
      cm in transplanted, and 3.4 cm in the listed-but-not-transplanted patients.
      Median time to transplant was 48 days. Recurrence rates were 19.8% for resection
      and 12.1% for all ITT patients. Overall, patient survival for resection versus
      ITT patients was similar (5-year survival of 53.0% vs 52.0%, not significant).
      However, for HCC patients with model end-stage liver disease (MELD) scores less
      than 10 and who radiologically met Milan or UCSF (University of California, San
      Francisco) criteria, 1-year and 5-year survival rates were significantly improved
      in resected patients. For patients with MELD score less than 10 and who met Milan
      criteria, 1-year and 5-year survival were 92.0% and 63.0% for resection (n = 26)
      versus 83.0% and 41.0% for ITT (n = 73, P = 0.036). For those with MELD score
      less than 10 and met UCSF criteria, 1-year and 5-year survival was 94.0% and
      62.0% for resection (n = 33) versus 81.0% and 40.0% for ITT (n = 78, P = 0.027).
      CONCLUSIONS: Among known HCC patients with preserved liver function, resection
      was associated with superior patient survival versus transplantation. These
      results suggest that surgical resection should remain the first line therapy for
      patients with HCC and compensated liver function who are candidates for
      resection.

PMID- 21865952
TI  - Safety of electroconvulsive therapy-duloxetine combination.

PMID- 21865953
TI  - Monocyte abnormality in catatonia: revisiting the immune theory of catatonia.

PMID- 21865954
TI  - Attitudes toward electroconvulsive therapy in Romanian psychiatrists.
AB  - Use of electroconvulsive therapy (ECT) is influenced by the attitudes of the
      psychiatrists. The aim of this pilot survey was to assess the knowledge about and
      attitudes toward ECT in Romanian psychiatrists. Participants of a scientific
      meeting were requested to fill a 29-item questionnaire. Answers reflecting false
      concepts or negative attitudes toward ECT were more than 20% in 15 of 21 items,
      which highlights the urgent need to improve psychiatrists' education and training
      about ECT in Romania.

PMID- 21865955
TI  - A cardiologist revisits electroconvulsive therapy: editorial comment.

PMID- 21865956
TI  - QT dispersion and rate-corrected QT dispersion during electroconvulsive therapy
      in elderly patients.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) induces increase of QT dispersion
      (QTD) and the rate-corrected QTD (QTcD), which are associated with increased risk
      of ventricular arrhythmias and cardiovascular mortality. The effects of
      electrical stimulus during ECT on QTD and QTcD in elderly patients are of
      considerable interest. OBJECTIVE: The purpose of this study was to clarify the
      differential effects of electrical stimulus caused by ECT on interbeat interval,
      QT interval, the rate-corrected QT (QTc) interval, QTD, and the QTcD under
      propofol anesthesia between younger and elderly patients with major depression.
      METHODS: Twenty younger psychiatric patients (aged 30-40 years) and 20 elderly
      patients (aged 65-75 years) scheduled for ECT were studied under propofol
      anesthesia. A 12-lead electrocardiogram was monitored to measure parameters.
      Muscle paralysis was achieved by administering 1-mg/kg succinylcholine
      intravenously, and the efficacy of ECT was determined by the tourniquet
      technique. RESULTS: The mean arterial pressure in the elderly was significantly
      higher than that of the younger patients from immediately to 2 minutes after
      electrical stimulus. The interbeat interval in the elderly was significantly
      lower than that of the younger patients from immediately to 1 minute after
      electrical stimulus. There was no statistically significant difference in the QT
      interval between the groups. The baseline value of QTc interval was higher than
      the normal limits, and the QTc interval in the elderly was significantly lower
      than that of the younger patients from immediately to 1 minute after electrical
      stimulus. The baseline value of QTD was higher than the normal limits, and the
      QTD in the elderly was significantly higher than that of the younger patients
      from immediately to 7 minutes after electrical stimulus. The baseline value of
      QTcD was higher than the normal limits, and the QTcD in the elderly was
      significantly higher than that of the younger patients from immediately to 7
      minutes after electrical stimulus. CONCLUSIONS: The QTc interval, QTD, and QTcD
      may be higher than the normal limits before anesthesia in patients with major
      depression. The QTD and QTcD in the elderly, which are associated with increased
      risks of ventricular arrhythmias, are higher than those of the younger patients
      after electrical stimulus during ECT. Electrical stimulus may induce further
      increased risks of cardiac events in elderly patients.

PMID- 21865957
TI  - Safety of electroconvulsive therapy in patients with a history of heart failure
      and decreased left ventricular systolic heart function.
AB  - OBJECTIVES: Patients with heart failure may experience psychiatric disorders for
      which electroconvulsive therapy (ECT) is indicated. Little is known, however,
      about the safety of ECT in these patients. We assessed the safety of ECT in
      patients with a history of heart failure and decreased left ventricular systolic
      heart function. METHODS: We conducted a retrospective review of the medical
      records of 35 patients with a history of heart failure and reduced left
      ventricular systolic heart function who underwent ECT at Mayo Clinic in
      Rochester, Minnesota, between January 1995 and December 2009. RESULTS: Of the 35
      patients, 18 (51%) were women. The median age was 77 years (range, 54-92 years).
      The median left ventricular ejection fraction was 30% (range, 15%-40%). The 35
      patients underwent 513 ECT sessions (median number of sessions per patient, 10;
      range, 1-44). The 35 patients tolerated ECT well. No patient died or experienced
      decompensated heart failure, myocardial ischemia, or myocardial infarction during
      or within 24 hours after an ECT session. Prophylactic intravenous beta-blockers
      were given to patients who, during previous ECT sessions, had marked hypertension
      (eg, systolic blood pressure >180-200 mm Hg) or a heart rate greater than 100
      beats per minute; overall, this prophylaxis was used in 26 patients during 413
      ECT sessions (80% of the total number of ECT sessions). Three patients
      experienced temporary, non-life-threatening cardiac arrhythmias. CONCLUSIONS:
      Electroconvulsive therapy was safe in 35 patients with a history of heart failure
      and decreased left ventricular systolic heart function treated at our
      institution.

PMID- 21865958
TI  - Continuous transthoracic echocardiography in a 93-year-old patient with
      hypertrophic cardiomyopathy during electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) is the treatment of choice for patients with a
      major depression disorder who have failed antidepressant therapy. Patients with
      hypertrophic cardiomyopathy (HCM) may have dynamic obstruction to left
      ventricular (LV) outflow. The effects on myocardial function during ECT and
      pretreatment with antihypertensive agents in patients with HCM and LV outflow
      tract obstruction gradients are unknown. We report the first use of continuous
      transthoracic echocardiography during ECT in a patient with HCM. We confirmed an
      outflow tract obstruction and showed a decrease in LV outflow tract gradients.
      Continuous transthoracic echocardiography monitoring using Doppler
      echocardiography during ECT is feasible.

PMID- 21865959
TI  - Electroconvulsive therapy for treatment of major depression in a 100-year-old
      patient with severe aortic stenosis: a 5-year follow-up report.
AB  - Although there is no specific age cutoff for electroconvulsive therapy (ECT) and
      no absolute contraindication to its use, very old age and the presence of cardiac
      conditions such as aortic stenosis are factors that may negatively affect the
      physician's decision to administer ECT in individual cases. We report our follow
      up of a 100-year-old woman with severe aortic stenosis who has received ECT
      safely for 5 years now. No cardiac complications have emerged during this period.
      Her prior unipolar depressive episode with catatonic features remains in
      remission with a single prophylactic ECT session every 3 months. We have observed
      from our experience with this unique case that periodic multidisciplinary re
      evaluation of the evolving risk-benefit profile of ECT is essential along with
      the inclusion of family members in this dialogue. Our patient's course
      illustrates that neither advanced age nor severe aortic stenosis is an absolute
      contraindication to ECT even over an extended period of time. Each case needs to
      be evaluated on its merits. To our knowledge, this case represents the oldest
      patient in the literature where ECT has been administered safely for such an
      extended period in the setting of severe aortic stenosis.

PMID- 21865960
TI  - Apparent prolongation of the motor seizure beyond the electroencephalographic
      seizure: something's afoot.

PMID- 21865961
TI  - Could monoamine oxidase inhibitors promote asystole in electroconvulsive therapy
      patients?

PMID- 21865962
TI  - Occurrence of robust psychotic symptoms after initial rTMS treatment session.

PMID- 21865963
TI  - Somatization disorder treated with electroconvulsive therapy.

PMID- 21865964
TI  - Protecting the skin and hair of the patient from the electrode gel with 1-layer
      semiporous gauze during electroconvulsive therapy.

PMID- 21865965
TI  - Electroconvulsive therapy: indications versus contexts.

PMID- 21865966
TI  - Benzodiazepine-modified electroconvulsive therapy (ECT).

PMID- 21865968
TI  - Nodularity of the small intestine in a child with systemic mastocytosis
      associated with hyperimmunoglobulin M syndrome.

PMID- 21865967
TI  - Stimulus dosing in electroconvulsive therapy.

PMID- 21865969
TI  - Late adolescent linear growth pattern in pediatric-onset inflammatory bowel
      disease.
AB  - The late adolescent linear growth pattern of pediatric patients with inflammatory
      bowel disease (IBD) has rarely been studied. We retrospectively reviewed the
      height measurements of 475 patients with IBD at 16, 18, and 20 years old for
      girls, and 18 and 20 years old for boys. We also compared Bayley-Pinneau bone age
      predicted and -measured adult heights. Female patients had mean height-for-age z
      scores of -0.25 +/- 1.0 at 16 years and -0.23 +/- 1.0 at 18 years (P = 0.189);
      boys had z scores of -0.30  +/- 1.1 at 18 years and -0.26 +/- 1.0 at 20 years,
      respectively (P = 0.105). Bayley-Pinneau height predictions were 1.5 and 2.4 cm
      greater than measured height for 18-year-old girls (P = 0.060) and 20-year-old
      boys (P = 0.017), respectively. Our data indicate that most patients with IBD
      attain adult height within normal timing for the population. Hence, early
      identification of growth impairment is critical to appropriate management in IBD.

PMID- 21865970
TI  - Inter- and intraobserver agreement in 24-hour combined multiple intraluminal
      impedance and pH measurement in children.
AB  - OBJECTIVES: Assessment of intra- and interobserver agreement in multiple
      intraluminal impedance (MII) measurement between investigators from different
      institutions. METHODS: Twenty-four 18- to 24-hour MII tracings were randomly
      chosen from 4 different institutions (6 per center). Software-aided automatic
      analysis was performed. Each result was validated by 2 independent investigators
      from the 4 different centers (4 investigator combinations). For intraobserver
      agreement, 6 measurements were analyzed twice by the same investigator. Agreement
      between investigators was calculated using the Cohen kappa coefficient. RESULTS:
      Interobserver agreement: 13 measurements showed a perfect agreement (kappa >
      0.8); 9 had a substantial (kappa 0.61-0.8), 1 a moderate (kappa coefficient 0.41
      to 0.6), and 1 a fair agreement (kappa coefficient 0.11-0.4). Median kappa value
      was 0.83. Intraobserver agreement: 5 tracings showed perfect and 1 showed a
      substantial agreement. The median kappa value was 0.88. CONCLUSIONS: Most
      measurements showed substantial to perfect intra- and interobserver agreement.
      Still, we found a few outliers presumably caused by poorer signal quality in some
      tracings rather than being observer dependent. An improvement of analysis results
      may be achieved by using a standard analysis protocol, a standardized method for
      judging tracing quality, better training options for method users, and more
      interaction between investigators from different institutions.

PMID- 21865971
TI  - Long-term efficacy of low-dose tricyclic antidepressants for children with
      functional gastrointestinal disorders.
AB  - OBJECTIVE: The aim of the study was to determine the long-term efficacy of the
      tricyclic antidepressant (TCA) drugs amitriptyline or imipramine in treating
      functional gastrointestinal disorders (FGIDs) in pediatric patients. MATERIALS
      AND METHODS: A retrospective chart review of children with a diagnosis of
      irritable bowel syndrome, functional dyspepsia, and functional abdominal pain
      diagnosed on the basis of the Rome III criteria was performed. Charts were
      analyzed for response to the medication and the duration of the response.
      RESULTS: A total of 98 patients took a TCA for an FGID. Of the 98 patients, 77
      patients (78.6%) responded to the treatment for an average of 10.73 (range 1-45)
      months. CONCLUSIONS: TCAs are effective in treating FGIDs in pediatric patients
      for a long duration.

PMID- 21865972
TI  - Micronutrient deficiencies in patients with typical and atypical celiac disease.
AB  - OBJECTIVE: The extent of the digestive/absorptive involvement in atypical
      presentation of celiac disease (CD) is not always clear. The aim of the study was
      to assess nutritional status of iron (Fe), copper (Cu), and zinc (Zn) in patients
      with typical CD (TCD) and atypical CD (ACD). PATIENTS AND METHODS: A cross
      sectional study was done in patients with TCD, ACD, and healthy controls (HC).
      Hemoglobin, serum ferritin, free erythrocyte protoporphyrin, Fe, Cu,
      ceruloplasmin, Zn, anti-endomysial antibodies, and anti-tissue transglutaminase
      antibodies were measured. Data were analyzed by Kruskal-Wallis, principal
      component analysis, and linear discriminant analysis. RESULTS: : One hundred nine
      individuals were studied (54 TCD, 19 ACD, 36 HC); mean age  +/-  standard
      deviation was 23 +/- 15.8 (range 1.6-75.4) years. Median and range of hemoglobin
      were 12.8 g/dL (8.1-17.6) in TCD, 12.4 g/dL (10.5-14.5) in ACD, and 13.6 g/dL
      (11.1-16.7) in HC (P < 0.0001); serum ferritin was 17.7 MUg/L (2.9-157), 10.8
      MUg/L (2.7-39.8), and 28.7 MUg/L (4.5-127.2), respectively (P < 0.01). Cu was 105
      MUg/dL (60-185), 97.5 MUg/dL (40-130), and 125 MUg/dL (80-205), respectively (P <
      0.05). Ceruloplasmin was 21.6  mg/dL (14.2-73.2), 22.6  mg/dL (0.9-34.3), and
      32.1 mg/dL (5.8-72.6), respectively (P < 0.01). There were no differences in Fe,
      free erythrocyte protoporphyrin, and Zn. Principal component analysis showed that
      58% of observed variability was explained by Fe and Cu indicators. Linear
      discriminant analysis revealed differences between CD and HC (P < 0.0001), with
      high values of correct classification for TCD (73%) and HC (72%), but not ACD
      (16%), which were mostly classified as TCD (79%). CONCLUSIONS: Deficiency of
      micronutrients was found both in typical as well as in atypical cases.

PMID- 21865973
TI  - Clinical and manometric characteristics of Allgrove syndrome.
AB  - OBJECTIVE: The association of adrenocorticotropic hormone (ACTH) insensitivity
      with achalasia and alacrimia (Allgrove syndrome, 3A) constitutes a rare
      multisystem disorder. Its evolution is not well known. The aim of this study was
      to describe clinical and esophageal manometric characteristics and outcomes in
      Allgrove syndrome. PATIENTS AND METHODS: This multicenter retrospective study
      compared clinical and manometric characteristics at diagnosis and on follow-up of
      9 children presenting with 3A (mean age at diagnosis 7.1 years) with those of 9
      children with idiopathic achalasia (IA) (mean age at diagnosis 8.3 years).
      RESULTS: At the time of diagnosis, 3 children with 3A presented with no digestive
      or respiratory signs because they were identified during a family screening; 1
      remained asymptomatic 8 years later. ACTH levels were high in patients with 3A.
      All of the patients with IA were symptomatic at diagnosis. No significant
      difference was observed when comparing any of the manometric parameters of the
      first esophageal manometry of 3A with those of IA. Seven children with 3A were
      operated on using the Heller procedure, completed by pneumatic esophageal
      dilation in 2 of these 7. One patient with 3A was treated only by nifedipine.
      Failure of treatment was observed in 3 children with 3A and 1 child with IA,
      partial success in 4 with 3A and 1 with IA, and total success in 2 with 3A and 7
      with IA (P < 0.03). Control manometry showed that in the 3A group, partial
      success after surgery was always associated with abnormally low or normal lower
      esophageal sphincter (LES) pressure, whereas failure after surgery was associated
      with high LES pressure. CONCLUSIONS: Our data showed that 3A presented a more
      severe course than IA despite presymptomatic diagnosis in cases of family
      screening. The high LES pressure noted in some patients with 3A is suggestive of
      a peculiar pattern in 3A affecting the LES and the lower part of the esophagus.

PMID- 21865974
TI  - Quality of life and level of anxiety in youths with inflammatory bowel disease in
      Ireland.
AB  - OBJECTIVE: Little is known of the psychological well-being of youths diagnosed as
      having inflammatory bowel diseases (IBDs). Much of the literature available
      focuses on adults with IBD and those that focus on youths tend to use generic
      measures of health-related quality of life (QOL). The primary aim of this
      research is to obtain a profile of the IBD-related QOL and levels of anxiety of
      youths of ages 9 to 17 years presenting with IBD to a national hospital. It is
      also intended to examine the clinical utility of the IMPACT-III questionnaire.
      PATIENTS AND METHODS: A questionnaire battery containing the IMPACT-III
      questionnaire and the Spence Children's Anxiety Scale (SCAS) was posted to all of
      the patients on the database of the gastrointestinal clinic between the ages of 9
      and 17 years (n = 215), resulting in an achieved sample size of 79 (response rate
      of 36.7%). RESULTS: It was found that 63% (n = 50) of participants had total
      IMPACT-III scores below the cutoff of 143, previously established for remission.
      In addition, 5 participants reported being unhappy with their lives. Thirty-nine
      percent (n = 31) of participants had elevated anxiety symptoms on >= 1 of the
      SCAS subscales. Anxiety level was found to be a significant predictor of QOL
      (beta = -0.616, P = 0.001). Qualitative feedback highlighted the variability of
      physical and psychological symptoms participants experience, feelings of anger or
      embarrassment around the condition, and posed numerous questions, indicating that
      there is a lack of knowledge among patients around IBD. CONCLUSIONS: These
      findings support the utility of screening patients with IBD for psychological
      difficulties and estimates of QOL. Further research and group interventions are
      recommended.

PMID- 21865975
TI  - Validation of an instrument to measure quality of life in British children with
      inflammatory bowel disease.
AB  - OBJECTIVE: To validate IMPACT-III (UK), a health-related quality of life (HRQoL)
      instrument, in British children with inflammatory bowel disease (IBD). PATIENTS
      AND METHODS: One hundred six children and parents were invited to participate.
      IMPACT-III (UK) was validated by inspection by health professionals and children
      to assess face and content validity, factor analysis to determine optimum domain
      structure, use of Cronbach alpha coefficients to test internal reliability, ANOVA
      to assess discriminant validity, correlation with the Child Health Questionnaire
      to assess concurrent validity, and use of intraclass correlation coefficients to
      assess test-retest reliability. The independent samples t test was used to
      measure differences between sexes and age groups, and between paper and
      computerised versions of IMPACT-III (UK). RESULTS: IMPACT-III (UK) had good face
      and content validity. The most robust factor solution was a 5-domain structure:
      body image, embarrassment, energy, IBD symptoms, and worries/concerns about IBD,
      all of which demonstrated good internal reliability (alpha = 0.74-0.88).
      Discriminant validity was demonstrated by significant (P  < 0.05, P < 0.01)
      differences in HRQoL scores between the severe, moderate, and inactive/mild
      symptom severity groups for the embarrassment scale (63.7 vs 81.0 vs 81.2), IBD
      symptom scale (45.0 vs 64.2 vs 80.6), and the energy scale (46.4 vs 62.1 vs
      77.7). Concurrent validity of IMPACT-III (UK) with comparable domains of the
      Child Health Questionnaire was confirmed. Test-retest reliability was confirmed
      with good intraclass correlation coefficients of 0.66 to 0.84. Paper and computer
      versions of IMPACT-III (UK) collected comparable scores, and there were no
      differences between the sexes and age groups. CONCLUSIONS: IMPACT-III (UK)
      appears to be a useful tool to measure HRQoL in British children with IBD.

PMID- 21865976
TI  - Role of gastroesophageal reflux in children with unexplained chronic cough.
AB  - OBJECTIVE: The relation between respiratory symptoms and gastroesophageal reflux
      (GER) is a matter of contention and debate, with limited data in children to
      substantiate or refute cause and effect. Moreover, there are few data on the
      relation between nonacid reflux and chronic cough in childhood. We aimed to
      describe the type and physical characteristics of reflux episodes in children
      with unexplained chronic cough. PATIENTS AND METHODS: Forty-five children with
      chronic cough underwent 24-hour multichannel intraluminal impedance-pH monitoring
      (MII-pH monitoring). Symptom association probability (SAP) characterized the
      reflux-cough association. Twenty children with erosive reflux disease (ERD)
      served as controls. RESULTS: Twenty-four children had cough-related reflux (CRR),
      with 19 having no gastrointestinal symptoms. Twenty-one had cough-unrelated
      reflux (CUR). CRR and ERD had increased acid (AR), weakly acidic (WAc), and
      weakly alkaline (WAlk) reflux. Esophageal acid exposure time and acid clearance
      time were higher in ERD than in CRR and CUR. In the CRR group, of 158 cough
      episodes related to reflux episodes, 66% involved AR, 18% WAc, and 16% WAlk.
      Seventeen children had positive SAP, 7 for AR, 5 for both AR and WAc, 4 for both
      WAc and WAlk, and 1 for WAlk. CONCLUSIONS: In children with unexplained chronic
      cough, asymptomatic acid and nonacid GER is a potential etiologic factor. The
      increased acid exposure time and delayed acid clearance characteristic of ERD are
      absent in cough-related GER. MII-pH monitoring increases the likelihood of
      demonstrating a temporal association between the cough and all types of reflux.

PMID- 21865977
TI  - Safety of percutaneous endoscopic gastrostomy in medically complicated infants.
AB  - BACKGROUND AND OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) tubes have
      been placed in children for more than 2 decades to provide nutrition to those
      unable to adequately and safely feed orally. Despite the well-documented success
      of PEG placement in older children, there is only 1 published article documenting
      the safety of PEG placement in small infants. In all children, PEG studies
      demonstrate the major complication rate to vary from 0.5% to 17%. The objective
      of this study was to evaluate the incidence of acute complications of PEG
      placement in medically complicated infants with a weight of less than 6 kg.
      PATIENTS AND METHODS: : We reviewed the charts of all infants cared for in the
      neonatal intensive care unit of Wheaton Franciscan Health Care-St Joseph's
      Regional Hospital, Milwaukee, WI, who received a PEG tube between January 2001
      and June 30, 2008. RESULTS: Forty infants with a mean gestational age of 29 weeks
      (range 23-41 weeks) with a mean weight of 3250 g (range 2100-5600 g) at time of
      PEG placement were included. The primary indication for most infants was
      dysphagia or inability to orally feed safely. A PEG was successfully placed in 38
      of 40 (95%) infants. There was 1 major complication: a 38-week infant with Prader
      Willi syndrome developed a pneumomediastinum caused by a tear at the upper
      esophageal sphincter. In a second infant the PEG bumper could not be passed
      beyond the upper esophageal sphincter. Sixteen infants had other surgical
      procedures performed at the time of PEG placement. For those infants only having
      a PEG placed, the mean procedure time was 10 minutes. CONCLUSIONS: PEG placement
      is both feasible and safe in small, medically complicated infants.

PMID- 21865978
TI  - Evaluation of guidelines for management of familial adenomatous polyposis in a
      multicenter pediatric cohort.
AB  - OBJECTIVE: To retrospectively assess, in a pediatric multicenter cohort,
      guidelines for the management of familial adenomatous polyposis (FAP). METHODS:
      Ten centers from the French-speaking Pediatric Gastroenterology Hepatology and
      Nutrition Group provided follow-up data on patients up to 18 years of age.
      Clinical records, genetic test results, endoscopy with histopathology
      examination, and therapeutic modalities were reviewed. RESULTS: A total of 70
      children from 47 families were included. When initial consultation resulted from
      a surveillance program because of an affected family member, 12 of 59 children
      were already symptomatic. Among 11 patients whose initial consultation was based
      only on symptoms, families were unaware at the time of a familial FAP history for
      7 children, whereas only 4 cases were sporadic. A panel of 27 different
      pathogenic adenomatous polyposis coli (APC) germ-line mutations and large genomic
      deletions were identified in 43 families. Extracolonic manifestations were found
      in half of the patients. As part of the standard practice for initial screening,
      the entire cohort underwent colonoscopy, which revealed adenoma above an intact
      rectosigmoid in 8 cases. Prophylactic colectomy was performed in 42 cases; high
      grade dysplastic adenoma and 1 invasive carcinoma were detected in 6 children.
      For timing of surgery, indications were in accordance with recent international
      guidelines. CONCLUSIONS: Defining optimal screening and therapeutic modalities in
      pediatric FAP cohorts is a challenge. Specific advice for genetic screening,
      endoscopy surveillance, and type of surgery based on recent guidelines is
      recommended.

PMID- 21865979
TI  - Molecular fingerprints of the human fecal microbiota from 9 to 18 months old and
      the effect of fish oil supplementation.
AB  - OBJECTIVES: The aim of this study was to monitor changes in the fecal microbiota
      from 9 to 18 months and to investigate the effect of increasing dietary n-3
      polyunsaturated fatty acids on the fecal microbiota. PATIENTS AND METHODS: In a
      double-blind controlled trial with random allocation to daily supplementation
      with 5 mL of fish oil (FO) or sunflower oil (SO) from 9 to 18 months of age,
      stool samples were collected from 132 healthy Danish infants. Molecular
      fingerprints of the bacterial DNA were obtained by terminal restriction fragment
      length polymorphism (T-RFLP). RESULTS: The T-RFLP profiles indicated that a few T
      RFs became dominant with age (bp100 and 102, both presumed to be Bacteroidetes)
      concomitantly with an overall increase in the microbial diversity (P = 0.04).
      Breast-feeding influenced both the T-RFLP profiles at 9 months and the changes
      from 9 to 18 months, and breast-feeding cessation during the trial modified the
      response to the dietary oils. In the FO group, the increase in bp102 was
      significantly reduced among children weaned before compared with those weaned
      during the trial (P = 0.027), whereas the increase in bp100 was reduced in the
      preweaned children of the SO group relative to those weaned during the trial (P =
      0.004). This was supported by intervention group differences in the changes in
      bp102 and bp100 among the earlier weaned children (P = 0.06 and P = 0.09,
      respectively). CONCLUSIONS: Cessation of breast-feeding played a dominant role
      relative to developmental changes in the fecal microbiota from 9 to 18 months. FO
      compared with SO supplementation affected changes in large bacterial groups, but
      only among children who had stopped breast-feeding before 9 months of age.

PMID- 21865981
TI  - Extramedullary acute myelocytic leukemia following liver transplantation for VOD
      with immunodeficiency.

PMID- 21865980
TI  - Results of extremely-low-birth-weight infants randomized to receive extra enteral
      calcium supply.
AB  - BACKGROUND AND OBJECTIVE: Bone mineral deficiency continues to occur in extremely
      low-birth-weight (ELBW) infants despite formulas enriched in calcium (Ca) and
      phosphorus (P). This study tested whether extra enteral Ca supplementation
      increases bone mineral content (BMC) and prevents dolichocephalic head flattening
      and myopia in ELBW infants. STUDY DESIGN: Infants 401 to 1000 birth weight
      receiving enteral feeds were randomized to receive feeds supplemented with Ca
      gluconate powder or pure standard feeds. The main outcome measures were the
      excretion of Ca and P by weekly spot urine measurements, the degree of
      dolichocephalic deformation (fronto-occipital diameter to biparietal diameter
      ratio, FOD/BPD) at 36 weeks postmenstrual age, and the BMC (by dual-energy x-ray
      absorptiometry) at discharge. Cycloplegic refraction was measured at 18 to 22
      months corrected age. PATIENTS AND RESULTS: Ninety-nine ELBW infants with a
      gestational age of 26 weeks (23-31) (median [minimum-maximum]) were randomized at
      a postnatal age of 12 days (5-23) weighing 790 g (440-1700). Urinary Ca excretion
      increased and P excretion decreased in the Ca-supplemented group. Total BMC was
      89.9 +/- 2.4 g (mean +/- SE) in the supplemented group and 85.2 +/- 2.6 g in the
      control group (P = 0.19). The FOD/BPD was 1.50 (1.13-1.69, mean +/- SD [standard
      deviation]) and 1.47 (1.18-1.64) in the supplemented and control groups, and the
      refraction 0.98  +/- 1.23 and 1.40 +/- 1.33 dpt (P = 0.68), respectively in 64
      ELBW infants (79% of survivors) at 2-year follow-up. CONCLUSIONS: Extra enteral
      Ca supplementation did not change BMC, head shape, or refraction. The decreased P
      excretion may reflect P deficiency in infants receiving extra Ca, preventing
      improved bone mineral accretion.

PMID- 21865982
TI  - Neonatal ichthyosis and sclerosing cholangitis syndrome: extremely variable liver
      disease severity from claudin-1 deficiency.

PMID- 21865983
TI  - Discussion: A patient death attributable to implant-related primary anaplastic
      large cell lymphoma of the breast.

PMID- 21865984
TI  - Discussion: A patient death attributable to implant-related primary anaplastic
      large cell lymphoma of the breast.

PMID- 21865985
TI  - The effects of hyperhomocysteinemia on the microcirculation of skin flaps.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for
      atherothrombotic disease and venous thrombosis. The effects of
      hyperhomocysteinemia on the microcirculation were studied in vascular diseases.
      The authors aimed to investigate the effects of hyperhomocysteinemia on the
      microcirculation of random-pattern skin flaps. METHODS: Twenty-two male Sprague
      Dawley rats, divided into two groups, were used in this study. The rats in group
      1 (control) were fed the TD.07112 diet, and the rats in group 2 (experimental
      group) were fed the TD.07114 diet, enriched in methionine for 30 days, to induce
      severe hyperhomocysteinemia. The plasma homocysteine, folic acid, vitamin B12,
      and vitamin B6 levels were evaluated on days 0 and 30. Distally based skin flaps
      were elevated on day 30 and evaluated by direct observation, microangiography,
      and light microscopy on day 37. RESULTS: Mean homocysteine blood levels were
      211.76 +/- 56.55 MUM/liter in group 2 and 14.48 +/- 2.00 MUM/liter in group 1 on
      day 30. The rate of necrosis was significantly higher in group 2 (59.00 +/- 4.38
      percent) compared with group 1 (32.54 +/- 6.13 percent; p < 0.01).
      Microangiographic findings were similar to direct observation results.
      Microvessel calibration was reduced in group 2. In group 1, structures of
      epidermis and dermis were normal; however, there was a slight mononuclear cell
      infiltration along with thick collagen fibers. A more prominent mononuclear cell
      infiltration with fields of loose epidermis, associated with inflammation and
      infiltration, were observed in group 2. CONCLUSION: The authors demonstrated, for
      the first time, that hyperhomocysteinemia severely suppressed the
      microvasculature of skin flaps, as shown by increased flap necrosis and reduced
      microvessel calibration in the experimental group.

PMID- 21865986
TI  - Anatomical study and clinical applications of free posterior tibial flap in the
      head and neck region.
AB  - BACKGROUND: The purpose of this study was to examine the anatomical features,
      clinical applications, and donor-site morbidities of the free posterior tibial
      flap. METHODS: The posterior tibial vascular system was examined in 30 fresh
      cadaver legs. This was followed by a clinical study involving patients with free
      posterior tibial flap reconstruction of defects in the head and neck region after
      tumor extirpation. Potential donor-site morbidities were studied at 1 year after
      surgery. RESULTS: The mean caliber of the posterior tibial artery and the venae
      comitantes in the cadaveric limbs was 2.7, 2.9, and 2.17 mm, respectively. The
      mean number of septocutaneous perforators was 2.85 per leg, clustering in the
      middle and distal thirds of the medial surface of the leg. The mean thickness of
      the skin and subcutaneous fat in the region was 4.43 mm. In the clinical study,
      64 patients with superficial cutaneous and mucosal defects were recruited. The
      majority of the patients had carcinoma of the oral cavity. All flaps survived.
      Three patients (4.7 percent) developed mild infection of the donor site. None of
      the patients have problems walking on level ground. There was no significant
      reduction in range of ankle movement, nor was there evidence of vascular
      compromise of the lower limb, either at rest or after exercise. CONCLUSIONS: The
      free posterior tibial flap is reliable because of its constant vascular anatomy.
      It is thin and pliable, making it particularly suitable for resurfacing
      superficial cutaneous and mucosal defects. Although skin grafting is required to
      repair the donor site, the associated morbidity is low. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 21865987
TI  - Reliable harvesting of a large thoracodorsal artery perforator flap with emphasis
      on perforator number and spacing.
AB  - BACKGROUND: Thoracodorsal artery perforator flaps are useful for covering
      extensive defects because of their generous donor-site dimensions. However, large
      flaps increase the risk of partial flap necrosis, and a reliable means of sizing
      thoracodorsal artery perforator flaps has not been devised. The authors reviewed
      a series of large thoracodorsal artery perforator flap transfers performed under
      various reconstructive conditions to evaluate surgical outcomes and placed
      emphasis on flap design and harvesting technique. METHODS: A consecutive series
      of large thoracodorsal artery perforator flaps (>20 cm long) performed between
      November of 2005 and March of 2010 were included in this study. Patient charts,
      operative records, and photographs were reviewed. RESULTS: A total of 20 flaps
      with an average size of 25 * 11 cm in 20 patients were identified; the largest
      flap measured 32 * 13 cm. The average number of perforators included was 2.6 per
      flap (range, one to four). Four different harvesting techniques were used,
      depending on perforator numbers and locations. All large flaps survived without
      sizable partial flap necrosis. Complications included wound dehiscence in one
      donor and two recipient sites; all healed after wound repair. Tip necrosis of a
      small area developed but healed with conservative wound care. CONCLUSIONS: This
      study reports the clinical safety of large thoracodorsal artery perforator flaps
      with customized thickness control, which can be reliably harvested beyond 20 cm
      in length by carefully considering perforator numbers and locations. To optimize
      tissue perfusion in these large flaps, effort is required to capture multiple
      perforators from various sources and to obtain an ideal arrangement. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 21865988
TI  - Perforator patterns of the anteromedial thigh flap.
AB  - BACKGROUND: The vascular anatomy of the anteromedial thigh flap has not been well
      defined. The purpose of this study was to determine the perforator patterns and
      vascular anatomy of this flap. METHODS: The perforators of the anteromedial thigh
      flaps and their origins were prospectively explored, documented, and mapped.
      RESULTS: Twenty-one of 100 thighs had no anteromedial thigh perforators. For the
      remaining thighs, there were two sources of perforators: the rectus femoris
      branch of the descending branch of the lateral circumflex femoris artery, and the
      superficial femoral artery. Perforators from the latter were short and small and
      thus less useful. Anteromedial thigh flaps based on rectus femoris branch
      perforators shared the same vascular pedicle as the anterolateral thigh flap and
      were thus clinically useful. These rectus femoris branch perforators, however,
      were present in only 51 percent of the patients. Their surface locations follow a
      similar pattern as the anterolateral thigh flap, with the majority of perforators
      near the midpoint, but an average of 3.2 cm medial to a line connecting the
      anterior superior iliac spine and the superolateral patella. Forty-three thighs
      had a single rectus femoris branch perforator and eight had two perforators.
      Sixty-six percent were septocutaneous and the rest traversed a thin layer of the
      rectus femoris muscle. CONCLUSIONS: The perforator patterns of the anteromedial
      thigh flap were examined and defined. It is best to plan the anteromedial thigh
      flap to complement the anterolateral thigh rather than to be the primary flap.

PMID- 21865989
TI  - Comparison of clinical outcomes between single- and multiple-perforator-based
      free thoracodorsal artery perforator flaps: clinical experience in 87 patients.
AB  - BACKGROUND: Although thoracodorsal artery perforator flaps have not gained
      popularity in the reconstructive era, the results of recent studies regarding the
      vascularity of thoracodorsal artery perforator flaps are promising. In the
      present study, the authors aimed to determine the clinical outcomes of free
      multiple-perforator versus single-perforator thoracodorsal artery perforator
      flaps. METHODS: Eighty-seven patients with various defects underwent
      reconstruction with free thoracodorsal artery perforator flaps. The flap was used
      for upper extremity reconstruction in 43 patients (49.4 percent), for head and
      neck reconstruction in 16 patients (18.4 percent), and for lower extremity
      reconstruction in 28 patients (32.2 percent). Of the 87 flaps, 48 (55.2 percent)
      were based on a single perforator, whereas 39 flaps (44.8 percent) were based on
      multiple perforators. The single- and multiple-perforator-based thoracodorsal
      artery perforator flaps were compared regarding clinical outcomes and morbidity.
      RESULTS: The morbidity rate was found to be significantly higher in the single
      perforator-based group. Of the patients in the single-perforator group, seven
      patients had transient venous congestion, five were heparinized and treated with
      leeches for permanent venous congestion, six had partial necrosis, and one had
      total necrosis. In the multiple-perforator-based group, two patients had
      transient venous congestion, and no partial or total necrosis was observed.
      CONCLUSION: Despite the fact that dominant perforators may often be absent, this
      study showed that a multiple-perforator-based thoracodorsal artery perforator
      flap may be more reliable with safe vascularity compared with a single-perforator
      based flap.

PMID- 21865990
TI  - Application of the dorsal metacarpal artery perforator flap for resurfacing soft
      tissue defects proximal to the fingertip.
AB  - BACKGROUND: The dorsal metacarpal artery perforator flap is a versatile solution
      for resurfacing soft-tissue defects of fingers. The authors present their
      experience in applying this flap for a variety of finger wounds for which
      conventional means may not be amenable. METHODS: Fifty-eight dorsal metacarpal
      artery perforator flaps were used to resurface 60 finger soft-tissue defects in
      56 patients over a 5-year period. Fifty-two patients were men and their average
      age was 37 years. This flap was used to reconstruct soft-tissue defects after
      debridement of infected wounds in 28 patients, traumatic wounds in 26 patients,
      and electrical burns in two patients. RESULTS: The average flap size was 4.6 *
      2.3 cm; 34 flaps were based on the second dorsal metacarpal artery perforator, 14
      were based on the third dorsal metacarpal artery perforator, and 10 were based on
      the fourth dorsal metacarpal artery perforator. Twenty-one flaps were used to
      resurface defects distal to the proximal interphalangeal joint, and 37 flaps were
      used to resurface defects over the proximal interphalangeal joint and proximal to
      it. Skin grafting was needed to close the donor defect in seven patients.
      Complications included venous congestion in six flaps and arterial insufficiency
      in three flaps, with total loss of two flaps and infection in one case.
      CONCLUSION: The dorsal metacarpal artery perforator flap is a thin, pliable flap
      that is simple to raise, has minimal donor-site morbidity, and can reliably cover
      soft-tissue defects up to the proximal half of the middle phalanx. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 21865991
TI  - Presurgical planning and time efficiency in orthognathic surgery: the use of
      computer-assisted surgical simulation.
AB  - Orthognathic procedures require extensive preoperative planning to maintain high
      fidelity of fabricated splints to anticipated skeletal and soft tissue changes.
      The authors report their use of the computer-assisted surgical simulation
      modeling system in preoperative planning and splint fabrication and the
      significant reduction in their overall preoperative time. Upper and lower bite
      registrations were sequentially created on a single bite jig with fast-drying bis
      acryl material, which was then mounted to a fiducial-based facebow for facial
      skeleton indexing. Indexing data were submitted, and occlusal splints were
      fashioned and returned to the senior surgeon. Between September 2010 and January
      2011, 10 consecutive patients were enrolled. Surgical indications included six Le
      Fort I advancements and four combined Le Fort I/bilateral sagittal split
      osteotomy cases. Average time for bite registration was 10 minutes 16 seconds +/-
      1 minute 33 seconds, with an additional 8 minutes 6 seconds +/- 4 minutes 45
      seconds needed for modeling and virtual splint confirmation. Six patients
      required cephalometric tracings, for an additional 12 minutes 50 seconds +/- 1
      minute 10 seconds. Average total session time for all patients was 26 minutes 14
      seconds +/- 9 minutes 13 seconds. Computer-assisted surgical simulation markedly
      decreased the time for preoperative splint planning and fabrication time, and had
      a positive impact on reimbursement rates for orthognathic surgery, as calculated
      on a per-hourly basis. The improved accuracy generated may lead to decreased
      operative times and improved outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 21865992
TI  - Prospective clinical study reveals significant reduction in triglyceride level
      and white blood cell count after liposuction and abdominoplasty and no change in
      cholesterol levels.
AB  - BACKGROUND: Triglyceride levels of 150 mg/dL or greater are known to be
      associated with an increased cardiovascular risk and metabolic syndrome. This
      study investigated the effect of liposuction and abdominoplasty on lipid levels,
      complete blood count, and other parameters. METHODS: A prospective study was
      undertaken among 322 consecutive patients (270 women and 52 men) who presented
      for liposuction (n = 229), abdominoplasty with liposuction (n = 87), and
      abdominoplasty without liposuction (n = 6). The mean body mass index was 26.6
      kg/m2 (range, 18.6 to 44.1 kg/m2). Ultrasonic liposuction using a superwet
      infusion technique was used in all cases, usually treating the lower body in
      women (64.4 percent) and the trunk in men (86.5 percent). RESULTS: Mean weight
      loss 3 months after liposuction was 2.2 lbs for liposuction alone (p < 0.001) and
      4.2 lbs for liposuction and abdominoplasty (p < 0.05). Mean fasting triglyceride
      level decreased 25.7 percent after liposuction (p < 0.001). The triglyceride
      level decreased 43.0 percent (n = 56, p < 0.001) after liposuction in patients
      with preoperative levels of 150 mg/dl or greater. There was a significant
      decrease in white cell count after both liposuction and
      liposuction/abdominoplasty (p < 0.001). There were no significant changes in
      total, low-density lipoprotein, or high-density lipoprotein cholesterol. Fasting
      glucose was unchanged. CONCLUSIONS: A significant (p < 0.001) reduction in
      triglyceride level in patients with elevated preoperative levels and a
      significant decrease in leukocyte count (p < 0.001) are favorable metabolic
      effects of liposuction and liposuction/abdominoplasty. Cholesterol levels are
      unaffected. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 21865993
TI  - Discussion: Prospective clinical study reveals significant reduction in
      triglyceride level and white blood cell count after liposuction and
      abdominoplasty and no change in cholesterol levels.

PMID- 21865994
TI  - Trunk, abdomen, and pressure sore reconstruction.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Describe the principles of wound closure, torso reconstruction, and
      pressure sore reconstruction. 2. Outline standard options to treat defects of the
      chest, abdomen, and back and pressure ulcers in all anatomical areas. 3. Manage
      and prevent pressure ulcers. SUMMARY: Chest wall reconstruction is indicated
      following tumor resection, radiation wound breakdown, or intrathoracic sepsis.
      Principles of wound closure and chest wall stabilization, where indicated, are
      discussed. Principles of abdominal wall reconstruction continue to evolve with
      the introduction of newer bioprosthetics and the application of functional
      concepts for wound closure. The authors illustrate these principles using
      commonly encountered clinical scenarios and guidelines to achieve predictable
      results. Pressure ulcers continue to be devastating complications to patients'
      health and a functional hazard when they occur in the bedridden, in patients with
      spinal cord injuries, and in patients with neuromuscular disease. Management of
      pressure ulcers is also very expensive. The authors describe standard options to
      treat defects of the chest, abdomen, and back and pressure ulcers in all
      anatomical areas. A comprehensive understanding of principles and techniques will
      allow practitioners to approach difficult issues of torso reconstruction and
      pressure sores with a rational confidence and an expectation of generally
      satisfactory outcomes. With pressure ulcers, prevention remains the primary goal.
      Patient education and compliance coupled with a multidisciplinary team approach
      can reduce their occurrence significantly. Surgical management includes
      appropriate patient selection, adequate debridement, soft-tissue coverage, and
      use of flaps that will not limit future reconstructions if needed.
      Postoperatively, a strict protocol should be adapted to ensure the success of the
      flap procedure. Several myocutaneous flaps commonly used for the surgical
      management of pressure are discussed. Commonly used flaps in chest and abdominal
      wall reconstruction are discussed and these should be useful for the practicing
      plastic surgeon.

PMID- 21865995
TI  - Volunteers in plastic surgery guidelines for providing surgical care for children
      in the less developed world: part II. Ethical considerations.
AB  - BACKGROUND: Many international volunteer groups provide free reconstructive
      plastic surgery for the poor and underserved in developing countries. An
      essential issue in providing this care is that it meets consistent guidelines for
      both quality and safety-a topic that has been addressed previously. An equally
      important consideration is how to provide that care in an ethical manner. No
      literature presently addresses the various issues involved in making those
      decisions. METHODS: With these ethical considerations in mind, the Volunteers in
      Plastic Surgery Committee of the American Society of Plastic Surgeons/Plastic
      Surgery Foundation undertook a project to create a comprehensive set of
      guidelines for volunteer groups planning to provide this type of reconstructive
      plastic surgery in developing countries. The committee worked in conjunction with
      the Society for Pediatric Anesthesia on this project. RESULTS: The Board of the
      American Society of Plastic Surgeons/Plastic Surgery Foundation has approved the
      ethical guidelines created for the delivery of care in developing countries. The
      guidelines address the variety of ethical decisions that may be faced by a team
      working in an underdeveloped country. These guidelines make it possible for a
      humanitarian effort to anticipate the types of ethical decisions that are often
      encountered and be prepared to deal with them appropriately. CONCLUSIONS: Any
      group seeking to undertake an international mission trip in plastic surgery
      should be able to go to one source to find a detailed discussion of the perceived
      needs in providing ethical humanitarian care. This document was created to
      satisfy that need and is a companion to our original guidelines addressing safety
      and quality.

PMID- 21865996
TI  - Discussion: Anaplastic large cell lymphoma and breast implants: results from a
      structured expert consultation process.

PMID- 21865997
TI  - Reduction mammaplasty, obesity, and massive weight loss: temporal relationships
      of satisfaction with breast contour.
AB  - BACKGROUND: Reduction mammaplasty is often performed on obese women. With the
      rise in bariatric procedures, secondary changes to breast contour are increasing.
      This study aims to investigate the temporal relationships of breast contour
      satisfaction with weight status. METHODS: One hundred ninety patients were
      examined. Patient demographics, comorbidities, body mass index, surgical history,
      and weight loss method used were evaluated. Patients who underwent reduction
      mammaplasty before massive weight loss were selected and administered a telephone
      survey (group I). Patients who did not undergo breast surgery before massive
      weight loss were selected as a control group (group II). RESULTS: Of the 15
      patients (7.9 percent) in group I, 14 completed the survey (93 percent). For
      group I, all patients felt the appearance of their breasts improved after
      reduction (p < 0.001) but felt appearance worsened or stayed the same after
      weight loss (p = 0.003). Seventy-one percent of patients were able to exercise
      more and 64 percent were able to lose weight on their own because of their
      reduction. For group II, 79 percent of patients felt the appearance of their
      breasts worsened or stayed the same after massive weight loss (p = 0.03).
      CONCLUSIONS: Most reduction patients before massive weight loss are glad they had
      the reduction and become more active but ultimately needed bariatric surgery to
      accomplish weight loss goals and are dissatisfied with breast contour following
      massive weight loss. Thus, patients who are considering bariatric procedures
      should be encouraged to pursue that operation before proceeding with reduction
      mammaplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 21865998
TI  - Anaplastic large T-cell lymphoma and breast implants: a review of the literature.
AB  - BACKGROUND: Anecdotal reports and one case-control study suggested an
      association, without evidence of causation, between breast implants and
      anaplastic lymphoma kinase-negative anaplastic large T-cell lymphoma (ALCL), a
      rare non-Hodgkin's lymphoma. This review summarizes the published evidence,
      including case reports and epidemiologic studies. METHODS: A PubMed search
      limited to English language articles was conducted using the search terms "breast
      implant" and "lymphoma," "primary T-cell breast lymphoma," or "breast implant and
      ALCL" to identify all published cases of breast-associated ALCL. RESULTS: A total
      of 18 publications were retrieved describing 27 cases of ALCL in breast implant
      recipients. Breast-associated ALCL occurred in women with and without implants.
      Approximately 78 percent of cases (21 of 27) were CD30 anaplastic lymphoma kinase
      negative, with an indolent clinical course. Both saline- and silicone-filled
      devices were identified; however, implant style and surface texture were largely
      unreported. The tumor stage at diagnosis was I in 16 of 27, II or higher in seven
      of 27, or unreported in four of 27. No prospective epidemiologic study has linked
      implants and ALCL; however, a single case-control study in Dutch women reported
      increased odds of association between ALCL and implants, and an estimated
      frequency of one in 1 million women with and without breast implants.
      CONCLUSIONS: An association, without evidence of causation, was reported between
      breast implants and ALCL. Further study is required to confirm this association.
      Breast-associated ALCL occurred rarely in women with and without breast implants
      and had a primarily indolent clinical course, which may provoke a revision of the
      World Health Organization nomenclature for lymphoma; however, aggressive clinical
      behavior was also reported. The cases of ALCL were not confined to a specific
      type of implant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

PMID- 21866000
TI  - Discussion: Minimally invasive component separation with inlay bioprosthetic mesh
      (MCSIB) for complex abdominal wall reconstruction.

PMID- 21865999
TI  - Functioning free gracilis myocutaneous flap transfer provides a reliable single
      stage facial reconstruction and reanimation following tumor ablation.
AB  - BACKGROUND: Ablative orofacial defects incorporating mimetic facial
      musculature/nerve cause hemifacial expressive dysfunction and considerable
      morbidity but are rarely reanimated immediately using free functioning gracilis
      myocutaneous flaps. METHODS: Disrupted buccal branches provided a recipient
      facial nerve for 24 gracilis reinnervations. An additional 15 free flaps were
      used for extensive composite defects. Smile outcome was graded according to
      Terzis' criteria after 2 years of recurrence-free follow-up. The effects of
      postoperative radiotherapy, integrity of the oral commissure, and double free
      flaps were compared. RESULTS: Eighteen patients completed 2 years' recurrence
      free follow-up; average smile outcome was Terzis grade 4 (mean, 3.8).
      Resection/reconstruction of the modiolus (five of 18 patients) tended to diminish
      outcome (Terzis grade 3, mean, 3.0; median, 3; versus Terzis grade 4, mean, 4.1;
      median, 5) compared with two free flaps performed simultaneously(mean, 3.56
      versus 4.14; median, 3 versus 5). Postoperative radiotherapy (eight of 18
      patients) had a more modest effect on outcome (Terzis grade 3, mean, 3.3; Terzis
      grade 4, mean, 4.1; median, 3 versus 5). CONCLUSION: Reconstruction of oncologic
      defects including expressive facial musculature/nerve with gracilis free
      functioning muscle transfer can restore oral continence and facial expression
      primarily. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 21866001
TI  - Long head of the triceps branch transfer to axillary nerve in C5, C6 brachial
      plexus injuries: anterior approach.
AB  - Shoulder abduction is a very complex movement and quite important for upper limb
      function, as more distal functions depend on a stable shoulder, especially in C5,
      C6 brachial plexus injuries. Various studies in the literature have emphasized
      the importance of improved functional outcome and shoulder reanimation with
      concomitant neurotization of suprascapular nerve and axillary nerve in C5, C6
      brachial plexus injuries. A number of approaches to axillary nerve transfer in
      brachial plexus injuries have been reported. The author describes an innovative
      anterior deltopectoral approach for axillary nerve transfers in five patients
      with C5, C6 brachial plexus injuries. The spinal accessory nerve was neurotized
      with the suprascapular nerve through a transverse supraclavicular incision. The
      axillary nerve and the long head of the triceps branch were identified through
      the anterior deltopectoral approach and neurotized at the posterior cord level.
      This approach gives easy access to other donors such as the medial pectoral,
      thoracodorsal, and median and ulnar nerves. Oberlin's transfer was also performed
      for elbow flexion by extending the deltopectoral incision. The regained shoulder
      active abduction (M5) averaged 120 degrees and active external rotation averaged
      65 degrees at the final follow-up of 26 months (average). This anterior
      deltopectoral approach is an excellent alternative for axillary nerve transfer in
      brachial plexus injuries and produces results comparable with those of other
      approaches. All brachial plexus surgeons must understand the anatomy and the
      relationship of the axillary nerve to the surrounding structures. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 21866002
TI  - Discussion: Oral prednisolone for infantile hemangioma: efficacy and safety using
      a standardized treatment protocol.

PMID- 21866003
TI  - Psychosocial changes after cosmetic surgery: a 5-year follow-up study.
AB  - BACKGROUND: Most studies examining psychosocial changes after cosmetic surgery
      have short follow-up periods and therefore provide limited information about long
      term effects of such surgery. Moreover, studies that identify whether preexisting
      patient characteristics are associated with poor psychosocial outcomes after
      cosmetic surgery are lacking. The current study provides information about both
      of these issues. METHODS: Questionnaire data from 130 female Norwegian cosmetic
      surgery patients were obtained before and 5 years after surgery. The
      questionnaire consisted of measures on appearance satisfaction, self-esteem,
      psychological problems, and patients' evaluation of the outcome of surgery. Data
      from a representative sample of 838 Norwegian women, aged 22 to 55 years, were
      used for comparison purposes. RESULTS: Analyses revealed an improvement in both
      general appearance satisfaction and satisfaction with the body part operated on 5
      years after surgery. A small increase in self-esteem was observed as well. High
      rates of preoperative psychological problems and low self-esteem were related to
      more negative changes in some of the psychosocial measures after surgery compared
      with patients with better psychological health. Furthermore, factors associated
      with the actual decision to undergo surgery were related to changes in
      psychological health and patients' evaluation of the outcome of surgery.
      CONCLUSIONS: This study indicates that cosmetic surgery has positive long-term
      effects on appearance-related variables. However, surgeons should be particularly
      aware of patients with psychological problems, as these may compromise patient
      satisfaction with the effects of cosmetic surgery. Factors affecting the decision
      itself to undergo cosmetic surgery may also be relevant for subsequent
      psychosocial outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 21866004
TI  - Discussion: Psychosocial changes after cosmetic surgery: a 5-year follow-up
      study.

PMID- 21866006
TI  - The privilege of advocacy: legislating awareness of breast reconstruction.

PMID- 21866005
TI  - Introducing the new PRS iPad app: the new world of plastic surgery education.

PMID- 21866011
TI  - The necessity of nasal layer closure in cleft palate repair: the unanswered
      enigma.

PMID- 21866012
TI  - Changing patterns in demography of cleft lip-cleft palate deformities in a
      developing country: the Smile Train effect--what lies ahead?

PMID- 21866014
TI  - The use of jejunal mesentery to provide additional soft-tissue coverage in
      esophageal reconstruction with a free jejunal flap: the mesenteric "wrap".

PMID- 21866016
TI  - Further information on anaplastic large cell lymphoma and breast implants.

PMID- 21866017
TI  - Unsuspected breast carcinoma in reduction mammaplasty specimens and the role of
      pathologic examination.

PMID- 21866018
TI  - Occult carcinoma in 866 reduction mammaplasties: preserving the choice of
      lumpectomy.

PMID- 21866021
TI  - Breast implant complication review: double capsules and late seromas.

PMID- 21866022
TI  - Double capsules: our experience with polyurethane-coated silicone breast
      implants.

PMID- 21866024
TI  - A combined anatomical and clinical study for quantitative analysis of the
      microcirculation in the classic perfusion zones of the deep inferior epigastric
      artery perforator flap.

PMID- 21866026
TI  - Correction of breast asymmetry does not exist, and the role of three-dimensional
      imaging remains a question.

PMID- 21866027
TI  - Form stability of the style 410 implant: definitions, conjectures, and the rest
      of the story.

PMID- 21866029
TI  - Psychology of plastic and reconstructive surgery: a systematic clinical review.

PMID- 21866031
TI  - Basic science review on adipose tissue for clinicians.

PMID- 21866033
TI  - The need for clinical trial registration information.

PMID- 21866036
TI  - Unsuitable patient selection in plastic surgery.

PMID- 21866037
TI  - Role of nuclear factor of activated T cell (NFAT) transcription factors in skin
      and vascularized cardiac allograft rejection.

PMID- 21866038
TI  - Demographic but not geographic insularity in HIV transmission among young black
      MSM.
AB  - OBJECTIVE: To understand patterns of HIV transmission among young black MSM and
      others in Mississippi. DESIGN: Phylogenetic analysis of HIV-1 polymerase (pol)
      sequences from 799 antiretroviral-naive persons newly diagnosed with HIV
      infection in Mississippi during 2005-2008, 130 (16%) of whom were black MSM aged
      16-25 years. METHODS: We identified phylogenetic clusters and used surveillance
      data to evaluate demographic attributes and risk factors of all persons in
      clusters that included black MSM aged 16-25 years. RESULTS: We identified 82
      phylogenetic clusters, 21 (26%) of which included HIV strains from at least one
      young black MSM. Of the 69 persons in these clusters, 59 were black MSM and seven
      were black men with unknown transmission category; the remaining three were MSM
      of white or Hispanic race/ethnicity. Of these 21 clusters, 10 included residents
      of one geographic region of Mississippi, whereas 11 included residents of
      multiple regions or outside of the state. CONCLUSION: Phylogenetic clusters
      involving HIV-infected young black MSM were homogeneous with respect to
      demographic and risk characteristics, suggesting insularity of this population
      with respect to HIV transmission, but were geographically heterogeneous. Reducing
      HIV transmission among young black MSM in Mississippi may require prevention
      strategies that are tailored to young black MSM and those in their sexual
      networks, and prevention interventions should be delivered in a manner to reach
      young black MSM throughout the state. Phylogenetic analysis can be a tool for
      local jurisdictions to understand the transmission dynamics in their areas.

PMID- 21866039
TI  - Challenges and opportunities for hepatitis C drug development in HIV-hepatitis C
      virus-co-infected patients.
AB  - The approval of the first direct-acting antivirals (DAAs) against the hepatitis C
      virus (HCV) has been eagerly expected for treating chronic hepatitis C in HIV
      individuals given that progression to cirrhosis and end-stage liver disease
      occurs faster in the co-infected population. The appropriate and judicious use of
      DAAs may provide cure to a large number of HIV-HCV patients. On the contrary, the
      widespread use of DAAs will occasionally be off-label or under unsatisfactory
      medical conditions, which may result in undesirable toxicities, drug interactions
      or selection of drug resistance in HCV. As a result of using first-generation
      DAAs in HIV-HCV-co-infected patients, a growing proportion of the remaining
      hepatitis C individuals will be those harboring non-HCV 1 genotypes or drug
      resistant HCV variants. Over time, the largest reservoir of HCV genotype 1
      patients will accumulate in resource-poor nations where access to hepatitis C
      therapy has been elusive and HIV treatment remains the primary health issue for
      the co-infected population.

PMID- 21866040
TI  - Impaired Bacillus Calmette-Guerin cellular immune response in HIV-exposed,
      uninfected infants.
AB  - OBJECTIVE: To evaluate cell-mediated immune response to Bacillus Calmette-Guerin
      (BCG) vaccination in uninfected, HIV-1-exposed infants, comparing it with
      unexposed children. DESIGN: It is designed as a cross-sectional study. METHODS:
      BCG-specific lymphoproliferation and T-cell subsets (CD4(+), CD8(+) and TCR
      gammadelta(+)) by flow cytometry and interleukin-10, interferon-gamma (IFN-gamma)
      and tumor necrosis factor-alpha (TNF-alpha) concentration by ELISA were analyzed
      in HIV-exposed and unexposed infants. Whole blood lymphocyte immunophenotyping
      and blood counts were performed in exposed children. Nonparametric tests were
      used (P < 0.05). RESULTS: Given the ontogeny of the immune system, exposed
      infants were separated into three groups according to age: exposed 1 (E1, aged
      6.1-8.8 months), E2 (aged 9.1-17.1 months) and E3 (aged 18.1-26.3 months).
      Unexposed infants (UE group) and E1 were matched for age. Cell proliferation was
      not different among the three exposed groups, neither for BCG nor for
      phytohemagglutinin (PHA)-stimulated cultures. Furthermore, BCG-stimulated
      lymphoproliferation was reduced in the E1 group in comparison with the UE group.
      T-lymphocyte subpopulations also showed differences, with the youngest HIV
      exposed groups (E1 and E2) showing a predominant proliferation of CD4(+) T cells
      in cultures with BCG, whereas E3 and UE groups had a robust gammadelta(+) T-cell
      expansion. There was lower IFN-gamma concentration in the samples from E1 group
      in comparison with all of the other groups. The unexposed infants showed higher
      TNF-alpha concentration in cultures with BCG and PHA in comparison with E1 group.
      CONCLUSION: BCG-specific T-cell proliferation was reduced in HIV-exposed
      uninfected infants and IFN-gamma concentration was lower in younger exposed
      infants, showing a delay in immune system maturation of HIV-exposed infants.

PMID- 21866041
TI  - Regulation of the susceptibility of HIV-1 to a neutralizing antibody KD-247 by
      nonepitope mutations distant from its epitope.
AB  - OBJECTIVE: A humanized neutralizing antibody, KD-247, targets the V3 loop of HIV
      1 Env. HIV-1 bearing the GPGR sequence at the V3 loop is potentially susceptible
      to KD-247. However, not all GPGR-positive HIV-1 isolates are neutralized by KD
      247. We examined the potential mechanism by which the susceptibility of HIV-1 to
      KD-247-mediated neutralization is regulated. DESIGN: We searched for nonepitope
      neutralization regulatory (NNR) mutations that sensitize GPGR-bearing HIV-1AD8 to
      KD-247 and mapped the locations of such mutations relative to the V3 loop.
      METHODS: : We generated a functional HIV-1AD8 Env library, and evaluated the
      viral susceptibility to KD-247 by measuring the half-inhibitory concentration
      (IC50) to KD-247 on TZM-bl cell assay. RESULTS: We identified nine KD-247
      sensitizing NNR mutations from 30 mutations in various regions of gp120,
      including the V1/V2 loop, C2, V3 loop, C4, and C5. They specifically affected KD
      247-mediated neutralization, as they did not affect the b12-mediated
      neutralization. When combined, the KD-247-sensitizing NNR mutations additively
      sensitized the virus to KD-247 by up to 10 000 folds. The KD-247-sensitizing NNR
      mutations increased KD-247 binding to the virion. Notably, the NNR mutation in C4
      coincides with the CD4-binding site of gp120. CONCLUSION: Given that most of the
      KD-247-sensitizing NNR mutations are remote from V3 loop, it is reasonable to
      hypothesize that the steady-state, local conformation of the V3 loop is regulated
      by the interdomain contact of gp120. Our mutational analysis complements
      crystallographic studies by helping provide a better understanding of the steady
      state conformation and the functional geometry of Env.

PMID- 21866042
TI  - Clinical research: a novel approach to regression substitution for handling
      missing data.
AB  - In clinical research, missing data are common. Imputed data are not real data but
      constructed values that should increase the sensitivity of testing. Regression
      substitution for the purpose of data imputation often did not provide a better
      sensitivity than did other methods. The objective of this study was to compare
      different methods of missing data imputation with that of regression substitution
      taking into account particular quality measures. A real data example with a 105
      value file was used. After randomly removing 5 values from the file, mean
      imputation and hot deck imputation were compared with regression substitution,
      taking account of the following requirements: (1) at least 2 independent
      variables be present in the equation, (2) no more than 1 datum per patient be
      missing, (3) no more than 5% of the data be missing, (4) more than 5% of the data
      be missing after randomly choosing 5% for regression-substitution deletion of the
      remainder, (5) only statistically significant variables be present in the
      regression model, and (6) no random errors be added to the imputed data. The test
      statistics after regression substitution were much better than those after the
      other 2 methods with F-values of 44.1 vs 29.4 and 30.1, and t-values of 7.6 vs
      5.6 and 5.7, and 3.0 vs 1.7 and 1.8. We conclude that regression substitution is
      a very sensitive method for imputing missing data provided particular quality
      measures are taken into account. 

PMID- 21866043
TI  - Potential adverse ultrasound-related biological effects: a critical review.
AB  - Ultrasound energy exerts important cellular, genetic, thermal, and mechanical
      effects. Concern about the safety of ultrasound prompted several agencies to
      devise regulatory limits on the machine output intensities. The visual display of
      thermal and mechanical indices during ultrasound imaging provides an aid to limit
      the output of the machine. Despite many animal studies, no human investigations
      conducted to date have documented major physiologic consequences of ultrasound
      exposed during imaging. To date, ultrasound imaging appears to be safe for use in
      regional anesthesia and pain medicine interventions, and adherence to limiting
      the output of ultrasound machines as outlined by the Food and Drug Administration
      may avoid complications in the future. This article reviews ultrasound-related
      biologic effects, the role of the regulatory agencies in ensuring safety with the
      use of ultrasound, and the limitations and implications of ultrasound use in
      humans.

PMID- 21866044
TI  - Immunohistofluorescence analysis of myofibroblast transdifferentiation in human
      corneas with bullous keratopathy.
AB  - PURPOSE: To detect the transdifferentiation of keratocytes into myofibroblasts in
      human corneas with bullous keratopathy and to examine the relation of such
      transdifferentiation to the clinical course of the disease. METHODS: Twenty
      patients with bullous keratopathy who underwent penetrating keratoplasty were
      enrolled in the study. Corneal buttons collected during surgery were examined for
      expression of alpha-smooth muscle actin (alphaSMA) by immunoblot analysis and by
      immunofluorescence analysis of whole-mount preparations. The course of bullous
      keratopathy was evaluated from clinical charts. RESULTS: Immunoblot analysis
      revealed a marked increase in alphaSMA expression in some corneas affected by
      bullous keratopathy. Immunofluorescence analysis revealed that alphaSMA was
      expressed in myofibroblastic cells in the stroma of 10 of the 20 corneas
      examined. Expression of alphaSMA was detected in subjects with a clinical history
      of corneal epithelial erosion from 12 months after the onset of clinical stromal
      edema. In contrast, in subjects without a clinical history of epithelial erosion,
      alphaSMA expression was not detected until at least 27 months after the onset of
      stromal edema. The incidence of alphaSMA expression in stromal cells was not
      significantly associated with topical steroid administration. CONCLUSIONS:
      Transdifferentiation of keratocytes into myofibroblasts was observed in human
      corneas affected by bullous keratopathy. Such transdifferentiation occurred
      earlier after the onset of stromal edema in patients with a clinical history of
      epithelial erosion than in those without such a history.

PMID- 21866045
TI  - Quality of nursing home care: perceptions of physicians, psychologists, and nurse
      practitioners.
AB  - Physicians, psychologists, and nurse practitioners rated the quality of nursing
      home care and the importance and feasibility of improvement strategies. Overall
      care was rated better than care of residents, followed by treatment of staff.
      Physicians rated care highest and nurse practitioners rated it lowest. In terms
      of suggestions for quality improvement, improving treatment of frontline staff
      and of families was rated as most important overall. We found differences across
      professional groups in recommended improvements, a finding that suggests the
      importance of interdisciplinary communication and developing an integrated
      viewpoint in optimizing care for older persons.

PMID- 21866046
TI  - Unique features of obstructive sleep apnea in World Trade Center responders with
      aerodigestive disorders.
AB  - OBJECTIVES: To compare obstructive sleep apnea (OSA) in World Trade Center (WTC)
      responders with aerodigestive disorders and snoring with non-WTC habitual
      snorers, and to distinguish features of OSA in a subset of responders with
      worsening of snoring after 9/11 from responders with previous habitual snoring.
      METHODS: Cross-sectional comparative study of 50 WTC Medical Monitoring and
      Treatment Program responders with aerodigestive disorders and snoring and 50
      nonresponders with snoring. Responders with worsening of snoring after 9/11 were
      compared with previous habitual snorers. RESULTS: : While there was a strong
      correlation between body mass index (BMI), weight, and Apnea + Hypopnea Index (r
      = 0.36, P = 0.001; r = 0.29, P = 0.044) in the nonresponders, no correlation
      between either BMI or weight and Apnea + Hypopnea Index was found in the
      responders. Responders with worsening of snoring after 9/11 had a significantly
      lower BMI than previous habitual snorers. CONCLUSION: Mechanisms other than
      obesity are important in the pathogenesis of OSA in WTC responders with
      aerodigestive disorders.

PMID- 21866047
TI  - Cancer mortality among aircraft manufacturing workers: an extended follow-up.
AB  - OBJECTIVE: Extended cancer follow-up among 77,943 aircraft workers. METHODS:
      Comprehensive exposure information enabled detailed classification of
      trichloroethylene (TCE), perchloroethylene (PCE), mixed solvents, and chromates
      exposure among these workers. RESULTS: Exposure to TCE, PCE, mixed solvents or
      chromates was not associated with increased cancer risk overall or for most
      cancer sites. Elevated rates compared with the general population were seen for
      non-Hodgkin lymphoma for PCE exposure, and colon and testicular cancers and
      multiple myeloma for mixed solvents exposure. Internal cohort analyses, however,
      showed no significant trends of increasing risk for these cancers with increasing
      years of exposure to TCE, PCE or mixed solvents. CONCLUSION: This large, long
      term cohort study with comprehensive exposure assessment found no consistent
      evidence of increased cancer risk overall or by site among aircraft workers,
      including those with long-term exposure to TCE, PCE, and mixed solvents.

PMID- 21866048
TI  - Efficacy of the revised NIOSH lifting equation to predict risk of low back pain
      due to manual lifting: expanded cross-sectional analysis.
AB  - OBJECTIVE: To evaluate whether the Revised NIOSH Lifting Equation (RNLE) is a
      valid tool for assessing risk of low back pain (LBP) due to manual lifting by
      using combined data from two cross-sectional studies of 1-year prevalence.
      METHODS: Results from a symptom and occupational history questionnaire and RNLE
      analysis for 677 subjects employed in 125 manual lifting jobs at nine industrial
      sites were combined from two studies. RESULTS: The odds of LBP increased as the
      lifting index (LI) increased from 1.0 to 3.0. A statistically significant odds
      ratio (OR) was found for both the 1 < LI <= 2 (OR = 1.81) and the 2 < LI <= 3
      categories (OR = 2.26). For jobs with an LI value greater than 3.0, however, the
      OR remained nonsignificant. The 2 < LI <= 3 group remained statistically
      significant after adjusting for age, gender, body mass index, and psychosocial
      factors. CONCLUSIONS: It is clear that as the LI increases, the risk of LBP
      increases. Longitudinal studies are needed.

PMID- 21866049
TI  - Respiratory symptoms necessitating spirometry among soldiers with
      Iraq/Afghanistan war lung injury.
AB  - OBJECTIVE: New-onset asthma rates are higher among US soldiers deployed to
      Iraq/Afghanistan than stateside, but overall respiratory symptom and spirometry
      rates among soldiers returning from Iraq/Afghanistan have not yet been addressed.
      We determined these rates in soldiers deployed to Iraq/Afghanistan versus troops
      stationed elsewhere. METHODS: Retrospective review of active-duty soldiers (2004
      to 2010) registered at Veterans Affairs Medical Center, Northport, New York, with
      Long Island/New York City zip codes. Subjects were examined by physicians or
      physicians' assistants. We counted number of spirometries, which required
      respiratory symptoms, and the provider was required to submit a diagnosis as part
      of the request process. RESULTS: Twenty-five percent of 7151 troops went to
      Iraq/Afghanistan (n = 1816) and 75% went elsewhere (n = 5335), with more smokers
      in the Iraq/Afghanistan group (16.1% vs 3.3%). Rates of symptoms and spirometry
      were 14.5% and 1.8%, for Iraq/Afghanistan, versus troops deployed elsewhere,
      respectively (P < 0.001). Both groups had similar forced expired volume in 1
      second/forced vital capacity ratios (78%). CONCLUSIONS: New-onset
      Iraq/Afghanistan war lung injury is common and rates of symptoms leading to a
      diagnosis requiring spirometry are high.

PMID- 21866050
TI  - Risk of lung cancer and occupational history: results of a French population
      based case-control study, the ICARE study.
AB  - OBJECTIVES: To assess the risk of lung cancer associated with occupations and
      industries. METHODS: A French population-based case-control study included 2923
      cases and 3555 controls. Lifelong occupational history was collected. Two lists
      of occupations known (A) or suspected (B) to be associated with lung cancer were
      used. Occupations and industries not included in these lists were also explored.
      RESULTS: Among men, the smoking-adjusted odds ratio was 1.97 for list A
      (attributable fraction: 12.3%), 1.4 for list B (due especially to
      carpenters/joiners and transport workers). Among unlisted occupations, excess
      risks were found for welders, plumbers, and several construction crafts. Odds
      ratios among women were elevated for list A, list B (due especially to
      launderers/dry cleaners), cleaners and hairdressers. CONCLUSIONS: These results
      confirm the role of known occupations and give insight into new occupational risk
      factors among men and women.

PMID- 21866052
TI  - Direct and indirect costs and potential cost savings of laparoscopic adjustable
      gastric banding among obese patients with diabetes.
AB  - OBJECTIVE: To estimate the time to breakeven and 5-year net costs for
      laparoscopic adjustable gastric banding among obese patients with diabetes taking
      direct and indirect costs into account. METHODS: Indirect cost savings were
      generated by quantifying the cross-sectional relationship between medical
      expenditures and absenteeism and between medical expenditures and presenteeism
      (reduced on-the-job productivity) and simulating indirect cost savings based on
      these multipliers and reductions in direct medical costs available in the
      literature. RESULTS: Time to breakeven was estimated to be nine quarters with and
      without the inclusion of indirect costs. After 5 years, net savings increase from
      $26570 (+/-$9000) to $34160 (+/-$10 380) when indirect costs are included.
      CONCLUSION: This study presented a novel approach for incorporating indirect
      costs into cost-benefit analyses. Application to gastric banding revealed that
      inclusion of indirect costs improves the financial outlook for the procedure.

PMID- 21866051
TI  - Risk and significance of chest radiograph and pulmonary function abnormalities in
      an elderly cohort of former nuclear weapons workers.
AB  - OBJECTIVE: To estimate prevalence and risk factors for International Labour
      Organization radiographic abnormalities, and assess relationship of these
      abnormalities with spirometry results in former Department of Energy nuclear
      weapons workers. METHODS: Participants were offered chest x-ray (CXR) and lung
      function testing. Three occupational medicine physicians read CXRs. RESULTS:
      Forty-five (5.9%) of 757 screened workers were found to have isolated parenchymal
      abnormalities on CXR and this rate is higher than that in many Department of
      Energy studies. Parenchymal and pleural and isolated pleural abnormalities were
      found in 19 (2.5%) and 37 (4.9%) workers, respectively, and these rates are lower
      than those in other Department of Energy studies to date. Lung function
      impairment was associated with radiographic abnormalities. CONCLUSIONS: This
      study found an elevated rate of parenchymal abnormalities compared to other DoE
      populations but the effect of age or other causes could not be ruled out.

PMID- 21866053
TI  - Effects of palladium nanoparticles on the cytokine release from peripheral blood
      mononuclear cells of palladium-sensitized women.
AB  - OBJECTIVE: To investigate the effects of palladium (Pd) nanoparticles on cytokine
      release from peripheral blood mononuclear cells (PBMCs) of control or Pd
      sensitized nonatopic women. METHODS: TNF-alpha, IL-5, IL-10 and IFN-gamma release
      and/or expression from PBMCs incubated in presence of 5 to 10 nm Pd nanoparticles
      or Pd salt (potassium hexachloropalladate) were determined by enzyme-linked
      immunosorbent assay and reverse transcription-polymerase chain reaction analysis.
      Transmission electronmicroscopy was performed. RESULTS: In lipopolysaccharide
      stimulated PBMCs from controls, Pd salt inhibited IFN-gamma and IL-10 release,
      whereas Pd nanoparticles enhanced IFN-gamma release and inhibited TNF-alpha
      secretion. In lipopolysaccharide-stimulated PBMCs from Pd-sensitized women
      showing high IFN-gamma release, Pd nanoparticles inhibited TNF-alpha release and
      Pd salt IL-10 release. TNF-alpha and IFN-gamma release and messenger RNA
      expression were correlated. Transmission electronmicroscopy demonstrated uptake
      of nanoparticles in the endocytic compartment and activation of autophagy.
      CONCLUSIONS: Palladium ions and nanoparticles exert different effects in vitro on
      the expression and release of cytokines.

PMID- 21866054
TI  - Association of shift work with physical activity among police officers: the
      Buffalo cardio-metabolic occupational police stress study.
AB  - OBJECTIVE: To examine relations of shift work with occupational, sports, and
      household physical activity (PA) among police officers. METHODS: Self-reported PA
      was assessed among 350 male and female officers (aged 27 to 66). Day, afternoon,
      or midnight shift was identified from daily payroll records. RESULTS: Shift work
      was associated with prevalence of hard-intensity (occupational and sport) PA
      among men, and very hard-intensity sport PA among women, with afternoon workers
      reporting the highest prevalence. Shift work was independently associated with
      total hours of hard-intensity PA among men and very hard-intensity PA among
      women, with afternoon workers reporting the most hours. CONCLUSION: Results
      indicated that hard and very hard-intensity PA varied significantly across shifts
      with afternoon workers being the most active.

PMID- 21866055
TI  - Infant stunting is associated with short maternal stature.
AB  - The objectives were to determine the range of maternal height associated with
      growth velocity of older infants and the magnitude of this association in an
      indigent population. Maternal height and infant length-for-age z scores (LAZ)
      were positively correlated at both 6 (n = 412, r = 0.324) and 12 (n = 388, r =
      0.335) months (P < 0.0001) and for maternal heights from 131 to 164  cm. Maternal
      height is independently associated with infant LAZ and stunting (LAZ <-2) at both
      6 and 12 months (P < 0.001) and with linear growth velocity from 6 to 12 months
      (P = 0.0023).

PMID- 21866056
TI  - Hemophagocytic lymphohistiocytosis with multiorgan involvement in children with
      chronic intestinal pseudo-obstruction receiving parenteral nutrition support.

PMID- 21866057
TI  - Benefits of a new pediatric triple-chamber bag for parenteral nutrition in
      preterm infants.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy, safety,
      flexibility, and ease of handling and use of the Ped3CB-A 300  mL, the first
      ready-to-use multichamber parenteral nutrition (PN) system, with optional lipid
      bag activation, specially designed for administration to preterm infants.
      MATERIALS AND METHODS: In this prospective, open-label, multicenter,
      noncomparative, phase III clinical trial, preterm infants were treated with
      Ped3CB-A for 5 to 10 consecutive days. RESULTS: A total of 113 preterm infants
      were enrolled in the study and 97 (birth weight 1382 +/- 520 g; gestational age
      31.2 +/- 2.5 weeks; postnatal age administration 5.6 +/- 6.1 days) were included
      in the per protocol analysis accounting for 854 perfusion days. Double-chamber
      bag activation was used for 32 perfusion days. Macronutrient, electrolyte, and
      mineral supplements were primarily administered through a Y-line or directly in
      the activated bag. In all, 199 additions (mainly sodium, 95%) were made to the
      Ped3CB-A bags on 197 infusion days (23.1%) in 43 infants (44.3%). More than 1 of
      these nutrients was added to the bag on only 1 perfusion day. Mean and maximum
      parenteral nutrient intakes were 2.8 +/- 0.7 and 3.6 +/- 0.8  g amino acids per
      kilogram per day, and 80 +/- 20 and 104 +/- 22  kcal . kg(-1) . day(-1). Mean
      weight gain represented 10.0, 21.5, and 22. 6 g . kg(-1) . day(-1) according to
      age at inclusion (0-3, 4-7, or >7 days of life). A visual analog scale was
      completed and produced positive results. No adverse events were attributable to
      the design of the Ped3CB-A system. CONCLUSIONS: Ped3CB-A provides easy-to-use,
      well-balanced, and safe nutritional support. Nutritional intakes and weight gain
      were within the recent PN recommendations in preterm infants.

PMID- 21866058
TI  - Hepatoblastoma as a result of APC gene mutation.

PMID- 21866059
TI  - Long-term outcome of liver disease-related fibrinogen aguadilla storage disease
      in a child.

PMID- 21866060
TI  - Plasma platelet-activating factor-acetyl hydrolase activity and the levels of
      free forms of biomarker of lipid peroxidation in cerebrospinal fluid of patients
      with aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Free radicals and lipid peroxidation are thought to be related to the
      vasospasm generation after subarachnoid hemorrhage (SAH). Plasma platelet
      activating factor-acetyl hydrolase (PAF-AH) degrades phospholipids with an
      oxidatively modified fatty acyl chain. OBJECTIVE: To compare plasma PAF-AH
      activity and free forms of biomarker of lipid peroxidation in cerebrospinal fluid
      (CSF) between patients with and without symptomatic vasospasm (SVS) after SAH.
      METHODS: The identification of PAF-AH in CSF was performed by Western blotting.
      The genotype at position 279 of the plasma PAF-AH gene was determined. The
      activities of PAF-AH and the levels of free 8-iso-prostaglandin F2alpha (free
      isoPs), free hydroxyoctadecadienoic acid (free HODE), and free
      hydroxyeicosatetraenoic acid (free HETE) in CSF were measured. RESULTS: The PAF
      AH in CSF was confirmed to be only the plasma type. The genotype of the plasma
      PAF-AH was not different between patients with and without SVS. Free isoPs, free
      HODE, and free HETE showed higher values in patients without SVS in 0 to 4 days
      and 5 to 9 days after SAH. The PAF-AH activity also was higher in patients
      without SVS in 0 to 4 days and 5 to 9 days after SAH. The associations between
      PAF-AH activity and free isoPs, and between PAF-AH activity and free HODE were
      significant. CONCLUSION: Oxidized lipids of lipoproteins and blood cell membranes
      produced by reactive oxygen species in CSF when SAH occurs may be the main source
      of lipid peroxidation. Plasma PAF-AH can hydrolyze oxidized phospholipids, and
      may attenuate the spreading of lipid peroxidation and participate in defense
      mechanisms against vasospasm after SAH.

PMID- 21866061
TI  - Quantitative angiographic comparison with the OSIRIS program between the direct
      and indirect revascularization modalities in adult moyamoya disease.
AB  - BACKGROUND: Up-to-date, quantitative angiographic measurement of
      revascularization extent after bypass surgery has not been reported. OBJECTIVE:
      To measure the extent of angiographic revascularization quantitatively 6 months
      postoperatively with the OSIRIS program (University Hospital of Geneva, version
      3.1). METHODS: A total of 75 bypass procedures were performed in 65 consecutive
      adult moyamoya disease patients, and 71 bypass surgeries in 61 adult moyamoya
      disease patients were studied 6 months postoperatively with angiography. We
      performed 5 different types of bypass surgeries: encephaloduroarteriosynangiosis
      (EDAS), superficial temporal artery-middle cerebral artery anastomosis (SMA), SMA
      with encephalomyosynangiosis (EMS), SMA with EDAS, and SMA with
      encephaloduroarteriomyosynangiosis (EDAMS). We also investigated single-photon
      emission computed tomography (SPECT) results after 6 months postoperatively and
      compared the angiographic revascularization extent with the SPECT results.
      RESULTS: The mean values for the extent of revascularization among 5 different
      bypass surgeries were as follows: 32.4% for EDAS only, 57.4% for SMA only, 58.4%
      for SMA with EMS, 66.1% for SMA with EDAS, and 70.8% for SMA with EDAMS. There
      was a statistically significant difference in the extent of revascularization
      among the 5 surgical modalities (P = .000) and between the EDAS-only group and
      various SMA groups (P = .000). Statistical analysis between angiographic
      revascularization extent and SPECT results demonstrated significant statistical
      correlation (P = .000). CONCLUSION: The extent of angiographic revascularization
      in adult moyamoya disease patients was highest in the SMA with EDAMS group and
      lowest in the EDAS-only group. In addition, angiographic revascularization extent
      was well correlated with the change in SPECT.

PMID- 21866062
TI  - Clinical neuroproteomics and biomarkers:  from basic research to clinical
      decision making.
AB  - Clinical neuroproteomics aims to advance our understanding of disease and injury
      affecting the central and peripheral nervous systems through the study of protein
      expression and the discovery of protein biomarkers to facilitate diagnosis and
      treatment. The general premise of the biomarker field is that in vivo factors
      present in either tissue or circulating biofluids, reflect pathological changes,
      and can be identified and analyzed. This approach offers an opportunity to
      illuminate changes occurring at both the population and patient levels toward the
      realization of personalized medicine. This review is intended to provide research
      driven clinicians with an overview of protein biomarkers of disease and injury
      for clinical use and to highlight methodology and potential pitfalls. We examine
      the neuroproteomic biomarker field and discuss the hallmarks and the challenges
      of clinically relevant biomarker discovery relating to central nervous system
      pathology. We discuss the issues in the maturation of potential biomarkers from
      discovery to Food and Drug Administration approval and review several platforms
      for protein biomarker discovery, including protein microarray and mass
      spectrometry-based proteomics. We describe the application of microfluidic
      technologies to the evolution of a robust clinical test. Finally, we highlight
      several biomarkers currently in use for cancer, ischemia, and injury in the
      central nervous system. Future efforts using these technologies will result in
      the maturation of existing and the identification of de novo biomarkers that
      could guide clinical decision making and advance diagnostic and therapeutic
      options for the treatment of neurological disease and injury.

PMID- 21866063
TI  - Styloidogenic jugular venous compression syndrome:  diagnosis and treatment: 
      case report.
AB  - BACKGROUND AND IMPORTANCE: Intracranial venous hypertension is known to be
      associated with venous outflow obstruction. We discuss the diagnosis and
      treatment of mechanical venous outflow obstruction causing pseudotumor cerebri.
      CLINICAL PRESENTATION: We report 2 patients presenting with central venous
      outflow obstruction secondary to osseous compression of the internal jugular
      veins at the craniocervical junction. The point of jugular compression was
      between the lateral tubercle of C1 and a prominent, posteriorly located styloid
      process. In both cases, catheter venography showed high-grade jugular stenosis at
      the level of C1 with an associated pressure gradient. The dominant jugular vein
      was decompressed after the styloid process was resected. Postoperative imaging
      confirmed resolution of the jugular stenosis and normalization of preoperative
      pressure gradients. In both cases, the symptoms of intracranial hypertension
      resolved. CONCLUSION: Intracranial venous hypertension may result from extrinsic
      osseous compression of the jugular veins at the skull base. Although rare, this
      phenomenon is important to recognize because primary stenting not only is
      ineffective but also may actually exacerbate the outflow obstruction. The osseous
      impingement of the dominant jugular vein can be relieved via a decompressive
      styloidectomy, and the clinical results can be excellent.

PMID- 21866064
TI  - Meningioma surgery in the elderly:  outcome and validation of 2 proposed grading
      score systems.
AB  - BACKGROUND: Although population age increases, published evidence on meningioma
      treatment in the elderly is scarce. OBJECTIVE: In order to improve selection for
      surgery, we investigated our patients' collective, using 2 proposed risk
      assessment systems, the Clinical-Radiological Grading System (CRGS) and the SKALE
      score (sex, Karnofsky, American Society of Anesthesiology [ASA] score, location,
      edema). METHODS: We retrospectively assessed morbidity and mortality in 164
      patients aged >= 65, operated on for an intracranial meningioma. Medical and
      surgical records were reviewed and analyzed. CRGS and SKALE scores were
      calculated. The ability of both CRGS and SKALE and all single factors to predict
      death within 12 months was analyzed by the use of multivariate logistic
      regression modeling. RESULTS: Eleven patients died (6.7%). Logistic regression
      for CRGS/SKALE showed a significant relationship with 12 months mortality. Age,
      Simpson resection grade, and sex were not significant predictors when
      investigated alone. In multivariate logistic regression, including all proposed
      factors, only concomitant disease and edema (CRGS) as well as ASA score and
      preoperative Karnofsky Performance Scale (SKALE) showed a significant
      relationship to mortality. After stepwise reduction of the full multivariate
      regression model to its significant terms, only concomitant disease and ASA
      remained significant for CRGS (P < .001) and SKALE (P = .003), respectively.
      CONCLUSION: Meningioma resection in the elderly is possible with some mortality.
      We were unable to reproduce the utility of 2 proposed grading systems for
      mortality prediction when extending to younger patients. In single-factor
      analysis, only concomitant disease and ASA score remained significant. The
      decision whether to operate should be taken individually. Patients with severe
      concomitant disease or high ASA score should be advised not to undergo surgical
      therapy independently from other factors.

PMID- 21866065
TI  - Comparative evaluation of percutaneous retrogasserian glycerol rhizolysis and
      radiofrequency thermocoagulation techniques in the management of trigeminal
      neuralgia.
AB  - BACKGROUND: Among the percutaneous procedures for the treatment of trigeminal
      neuralgia, percutaneous anhydrous glycerol rhizolysis (PRGR) and radiofrequency
      (RF) ablation of trigeminal neuralgia have stood the test of time. OBJECTIVE: A
      prospective study was conducted to compare PRGR and RF ablation techniques in
      patients with trigeminal neuralgia in terms of (1) efficacy of pain relief, (2)
      duration of pain relief and (3) side effects. METHODS: All patients presenting to
      our pain clinic for the first time for the treatment of trigeminal neuralgia were
      enrolled to receive either PRGR or RF ablation; the treatment was chosen by the
      patient. Demographic data, magnetic resonance imaging scan, relevant medical
      disease, amount of anhydrous glycerol, lesion temperature, and total duration of
      RF were noted. The presence or absence of cerebrospinal fluid egress, immediate
      pain relief, duration of pain-free period, need for repeat injection or
      additional peripheral nerve block, and recurrence of pain were also noted. The
      degree of pain relief was recorded every 3 months. Any complications during the
      procedure and side effects were also recorded. RESULTS: Seventy-nine patients
      underwent either PRGR (n = 40) or RF thermocoagulation (n = 39). A total of 23
      patients (58.9%) in the PRGR group and 33 patients (84.6%) in the RF group
      experienced excellent pain relief. The mean duration of excellent pain relief in
      the PRGR and RF groups was comparable. By the end of the study period, 39.1%
      patients in the PRGR group and 51.5% patients in the RF group experienced
      recurrence of pain. CONCLUSION: Both PRGR and RF techniques can achieve
      acceptable pain relief with minimal side effects.

PMID- 21866066
TI  - Surgical treatment of low-grade isthmic spondylolisthesis with transsacral
      fibular strut grafts.
AB  - BACKGROUND: The ideal surgical treatment for adult low-grade isthmic
      spondylolisthesis (ALIS) remains unknown. Isolated anterior and posterior
      procedures are popular but have resulted in equivocal outcomes, whereas combined
      anterior and posterior procedures are associated with higher complication rates
      despite improved outcome. OBJECTIVE: To evaluate the clinical and radiographic
      outcomes following the treatment of ALIS using a 1-stage posterior approach with
      posterior decompression and posterolateral arthrodesis combined with an interbody
      fibular allograft strut. METHODS: Fifteen patients underwent fusion by a single
      surgeon using our modified technique. Seven patients were female and 8 were male,
      with a mean age of 48 years. All patients were classified as Meyerding grade II
      slips and underwent a posterior approach only, a decompressive laminectomy, and a
      circumferential fusion with the use of a transsacral fibular allograft and a
      posterolateral instrumented fusion. Postoperative clinical and radiographic
      evaluations were performed at 3, 6, and 12 months, and then on an annual basis.
      RESULTS: The average follow-up interval was 61 months. Three complications were
      seen: a single dural tear, an L5 radiculopathy secondary to a malpositioned
      pedicle screw, and one patient with urinary retention. The spines of all patients
      were determined to be fused by the 6-month postoperative visit. All patients
      returned to their normal activities of daily living. Significant improvements in
      the visual analog score were seen at all follow-up intervals. CONCLUSION:
      Transsacral interbody fibular allograft can be used successfully to supplement a
      posterolateral instrumented fusion in selected patients with low-grade ALIS.

PMID- 21866069
TI  - Interdural hematoma extending from the clivus to the spinal epidural space in an
      intracranial aneurysm case.

PMID- 21866070
TI  - Primary stenting for stroke.

PMID- 21866071
TI  - The silk flow-diverting stent in the endovascular treatment of complex
      intracranial aneurysms:  technical aspects and midterm results in 24 consecutive
      patients.
AB  - BACKGROUND: The flow-diverting stent is a new option in endovascular therapy
      specifically designed for the endovascular reconstruction of a segmentally
      diseased artery. The safety of flow-diverting stents is still equivocal.
      OBJECTIVE: To evaluate the technical aspects, thromboembolic events, adjunctive
      therapies, and midterm results in patients with complex intracranial aneurysms
      treated with a flow-diverting stent (Silk; Balt Extrusion, Montmorency, France).
      METHODS: We retrospectively examined angiographic images and clinical reports of
      24 consecutive patients (29 stents) treated (n = 23) or attempted to treat (n =
      1) with a flow-diverting device in 2 Finnish centers between March 2009 and
      October 2010. RESULTS: The primary technical success rate was 67% (16/24).
      Adjunctive therapies were required in 6 (25%) patients, including 4 cases where
      intra-arterial abciximab was administered for the treatment of intraprocedural
      thromboembolic events. Technique-related complication rate and the 30-day
      mortality rate were each 4% (1/24). Follow-up imaging revealed 1 case of delayed
      in-stent thrombosis resulting in permanent disability of the patient, 1
      asymptomatic occlusion, and 1 asymptomatic stenosis of the stented artery.
      Complete occlusion of the aneurysm with fully patent parent artery was observed
      in 16 of the 23 aneurysms (70%) where follow-up images were available.
      CONCLUSION: Many previously untreatable cerebral aneurysms may be successfully
      treated with the Silk flow-diverting stent, but the associated risk of
      thromboembolic events is justifiable only if conventional endovascular or
      surgical treatment options are not applicable. Perioperative thromboembolic
      events should be prepared for and treated without unnecessary delays because they
      frequently respond to adjunctive medical therapy.

PMID- 21866072
TI  - The impact of Haemophilus influenzae serotype B resurgence on the epidemiology of
      childhood invasive Haemophilus influenzae disease in England and Wales.
AB  - This study describes the epidemiology of childhood invasive Haemophilus
      influenzae disease in England and Wales between 1994 and 2008. H. influenzae
      serotype b incidence was lowest in 1998 (0.26/100,000), rising to 1.8/100,000 in
      2002 before falling to 0.27/100,000 in 2008. During this period, nontype b H.
      influenzae disease remained stable, but there was a small year-on-year increase
      (3.4%/y; 95% CI: 1.4-5.5%) in incidence.

PMID- 21866073
TI  - Prognosti implications of pigment epithelial detachment in bevacizumab (avastin)
      treated eyes with age-related macular degeneration and choroidal
      neovascularization.
AB  - PURPOSE: To evaluate the response to primary bevacizumab treatment of eyes with
      age-related macular degeneration (AMD) and choroidal neovascularization (CNV)
      with a large pigment epithelial detachment (PED) component and to compare the
      increase in visual acuity and reabsorption of retinal fluid in PED eyes with eyes
      with CNV in AMD with a minimal to no PED component. METHODS: We reviewed 43
      consecutive eyes with CNV and AMD on primary bevacizumab therapy. There were 13
      eyes with a large PED component in AMD with CNV and 30 eyes with a minimal to no
      PED in CNV. Only patients with no previous treatment for AMD and those started on
      purely intravitreal bevacizumab treatment were taken in the study. Pigment
      epithelial detachment size, time to PED collapse, and retinal or subretinal fluid
      resolution were determined as was Early Treatment Diabetic Retinopathy Study
      vision. Time to resolution of intraretinal and subretinal fluid was compared
      between the PED group and the non-PED group using survival analysis. RESULTS: In
      AMD with CNV eyes having a large PED component, sub- and intraretinal fluid
      initially resolved faster than the sub-PED fluid (P = 0.03). The subretinal
      pigment epithelial fluid itself was highly resistant. Visual acuity improvement
      was similar in both groups. CONCLUSION: Despite monthly intravitreal bevacizumab
      injections for neovascular AMD patients with a large component PED, the majority
      had minimal to no response of the PED. Sub- and intraretinal fluid response was
      faster in neovascular AMD without large PEDs, but after 7 months, vision change
      and reabsorption of intra- and subretinal fluid were similar in the two groups.
      Sub- and intraretinal fluid response did not appear to be related to PED size.
      Bevacizumab was very effective in reducing more of the sub- and intraretinal
      fluid than the PED fluid in AMD with CNV.

PMID- 21866074
TI  - Vitreous inflammatory factors and serous macular detachment in branch retinal
      vein occlusion.
AB  - PURPOSE: To investigate whether vascular endothelial growth factor, soluble
      intercellular adhesion molecule-1 (sICAM-1), and pigment epithelium-derived
      factor are associated with serous retinal detachment (SRD) secondary to branch
      retinal vein occlusion. METHODS: The subjects were 44 branch retinal vein
      occlusion patients with macular edema and 16 controls. Patients were divided into
      2 groups by optical coherence tomography findings, that is, 18 patients with SRD
      and 26 with cystoid macular edema. The area of capillary nonperfusion was
      measured with fluorescein angiography and Scion Image software. Vitreous fluid
      samples obtained during pars plana vitrectomy were examined by enzyme-linked
      immunosorbent assay. RESULTS: The incidence of major branch retinal vein
      occlusion was significantly higher in SRD patients (17/18, 94%) than in cystoid
      macular edema patients (15/26, 58%, P = 0.007), while the nonperfused retinal
      area was significantly larger in SRD patients (P = 0.006). Vitreous fluid levels
      of vascular endothelial growth factor and soluble intercellular adhesion molecule
      1 (sICAM-1) showed a significant increase across the 3 groups (control group,
      cystoid macular edema group, and SRD group) (P trend < 0.001 and P trend < 0.001,
      respectively), while the pigment epithelium-derived factor level showed a
      significant decrease across the 3 groups (P trend < 0.001). CONCLUSION: An
      excessive increase of vascular permeability secondary to upregulation of vascular
      endothelial growth factor and soluble intercellular adhesion molecule-1 (sICAM-1)
      along with downregulation of pigment epithelium-derived factor may contribute to
      the development of SRD in BRVO patients.

PMID- 21866075
TI  - Characteristics of optical coherence tomographic hyperreflective foci in retinal
      vein occlusion.
AB  - PURPOSE: To evaluate the hyperreflective foci in branch retinal vein occlusion
      and central retinal vein occlusion depicted by spectral-domain optical coherence
      tomography (OCT). METHODS: Consecutive series of 73 eyes of 73 patients with
      retinal vein occlusion (58 branch retinal vein occlusion and 15 central retinal
      vein occlusion) who had Spectralis OCT images obtained were retrospectively
      reviewed, comparing color fundus photographs and fluorescein angiography.
      RESULTS: Hyperreflective foci were detected in 54 eyes (74.0%) by spectral-domain
      OCT, and hard exudates were detected in 17 eyes (23.3%) by color fundus
      photography. Hard exudates on the color photographs corresponded to the
      confluence of hyperreflective foci mainly around the outer plexiform layer in the
      unaffected areas on the spectral-domain OCT images, whereas fine hyperreflective
      foci were scattered in all retinal layers of the affected areas (P < 0.001). Most
      eyes with hyperreflective foci attached to the inner side of the external
      limiting membrane also had serous retinal detachment (P < 0.001). Compared with
      diabetic macular edema, we did not find subfoveal hard exudates in retinal vein
      occlusion. CONCLUSION: Hyperreflective foci delineated on spectral-domain OCT
      suggest the pathogenesis regarding the flow of extravasated blood constituents in
      retinal vein occlusion.

PMID- 21866076
TI  - Diagnostic and therapeutic challenges.

PMID- 21866077
TI  - The transplant library of randomized controlled trials and systematic reviews.

PMID- 21866084
TI  - National and state vaccination coverage among adolescents aged 13 through 17
      years--United States, 2010.
AB  - The Advisory Committee on Immunization Practices (ACIP) recommends that
      adolescents routinely receive meningococcal conjugate (MenACWY, 2 doses);
      tetanus, diphtheria, acellular pertussis (Tdap, 1 dose); and human papillomavirus
      (HPV, 3 doses) vaccines (influenza vaccine is recommended annually for all
      persons aged 6 months and older). CDC tracks vaccination coverage among
      adolescents aged 13 through 17 years through the National Immunization Survey-
      Teen (NIS-Teen). To provide updated vaccination coverage estimates, CDC analyzed
      2010 NIS-Teen data and compared results with 2009 NIS-Teen estimates. This report
      summarizes the results of that analysis, which found that coverage increased for
      all three of the routinely administered adolescent vaccines: Tdap from 55.6% to
      68.7%, MenACWY from 53.6% to 62.7%, (among females) >=1 dose of HPV from 44.3% to
      48.7%, and >=3 doses of HPV from 26.7% to 32.0%. Vaccination coverage varied
      widely among states; three states (Massachusetts, Rhode Island, and Washington)
      had coverage of >65% for >=1 dose of all three vaccines (Tdap, MenACWY, and HPV).
      Continued evaluation of vaccination-promoting initiatives, including state
      vaccination-financing policies, is needed to understand their impact on
      adolescent vaccination and to promote effective practices.

PMID- 21866085
TI  - State preemption of local tobacco control policies restricting smoking,
      advertising, and youth access--United States, 2000-2010.
AB  - Preemptive state tobacco control legislation prohibits localities from enacting
      tobacco control laws that are more stringent than state law. State preemption
      provisions can preclude any type of local tobacco control policy. The three broad
      types of state preemption tracked by CDC include preemption of local policies
      that restrict 1) smoking in workplaces and public places, 2) tobacco advertising,
      and 3) youth access to tobacco products. A Healthy People 2020 objective (TU-16)
      calls for eliminating state laws that preempt any type of local tobacco control
      law. A previous study reported that the number of states that preempt local
      smoking restrictions in one or more of three settings (government worksites,
      private-sector worksites, and restaurants) has decreased substantially in recent
      years. To measure progress toward achieving Healthy People 2020 objectives, this
      study expands on the previous analysis to track changes in state laws that
      preempt local advertising and youth access restrictions and to examine policy
      changes from December 31, 2000, to December 31, 2010. This new analysis found
      that, in contrast with the substantial progress achieved during the past decade
      in reducing the number of states that preempt local smoking restrictions, no
      progress has been made in reducing the number of states that preempt local
      advertising restrictions and youth access restrictions. Increased progress in
      removing state preemption provisions will be needed to achieve the relevant
      Healthy People 2020 objective.

PMID- 21866086
TI  - Prevention and control of influenza with vaccines: recommendations of the
      Advisory Committee on Immunization Practices (ACIP), 2011.
AB  - This document provides updated guidance for the use of influenza vaccines in the
      United States for the 2011-12 influenza season. In 2010, the Advisory Committee
      on Immunization Practices (ACIP) first recommended annual influenza vaccination
      for all persons aged >=6 months in the United States. Vaccination of all persons
      aged >=6 months continues to be recommended. Information is presented in this
      report regarding vaccine strains for the 2011-12 influenza season, the
      vaccination schedule for children aged 6 months through 8 years, and
      considerations regarding vaccination of persons with egg allergy. Availability of
      a new Food and Drug Administration (FDA)-approved intradermally administered
      influenza vaccine formulation for adults aged 18 through 64 years is reported.
      For issues related to influenza vaccination that are not addressed in this
      update, refer to the 2010 ACIP statement on prevention and control of influenza
      with vaccines and associated updates.

PMID- 21866087
TI  - Notes from the field: mortality among refugees fleeing Somalia--Dadaab refugee
      camps, Kenya, July-August 2011.
AB  - Refugee camps in Dadaab, Kenya, currently are receiving Somali refugees fleeing
      famine and armed conflict at a rate of approximately 1,400 refugees per day. New
      arrivals are at an elevated risk for mortality because of severe famine in
      Somalia, the dangerous journey, and overcrowding in the camps.

PMID- 21866088
TI  - Surveillance for violent deaths--National Violent Death Reporting System, 16
      states, 2008.
AB  - PROBLEM/CONDITION: An estimated 50,000 persons die annually in the United States
      as a result of violence-related injuries. This report summarizes data from CDC's
      National Violent Death Reporting System (NVDRS) regarding violent deaths from 16
      U.S. states for 2008. Results are reported by sex, age group, race/ethnicity,
      marital status, location of injury, method of injury, circumstances of injury,
      and other selected characteristics. REPORTING PERIOD COVERED: 2008. DESCRIPTION
      OF SYSTEM: NVDRS collects data regarding violent deaths obtained from death
      certificates, coroner/medical examiner reports, and law enforcement reports.
      NVDRS data collection began in 2003 with seven states (Alaska, Maryland,
      Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating;
      six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and
      Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in
      2005, and two in 2010 (Ohio and Michigan) for a total of 19 states. This report
      includes data from 16 states that collected statewide data in 2008; data from
      California are not included in this report because NVDRS was implemented only in
      a limited number of California cities and counties rather than statewide. Ohio
      and Michigan are excluded because they did not begin data collection until 2010.
      RESULTS: For 2008, a total of 15,755 fatal incidents involving 16,138 deaths were
      captured by NVDRS in the 16 states included in this report. The majority (58.7%)
      of deaths were suicides, followed by homicides and deaths involving legal
      intervention (i.e. deaths caused by police and other persons with legal authority
      to use deadly force, excluding legal executions) (26.4%), deaths of undetermined
      intent (14.5%), and unintentional firearm deaths (0.4%). Suicides occurred at
      higher rates among males, American Indians/Alaska Natives (AI/ANs), non-Hispanic
      whites, and persons aged 45-54 years. Suicides occurred most often in a house or
      apartment (70.6%) and involved the use of firearms (51.5%). Suicides were
      precipitated primarily by mental health (45.4%), intimate partner (30.9%), or
      physical health problems (22.6%), or by a crisis during the preceding 2 weeks
      (27.9%). Homicides occurred at higher rates among males and persons aged 20-24
      years; rates were highest among non-Hispanic black males. The majority of
      homicides involved the use of a firearm (65.8%) and occurred in a house or
      apartment (52.5%) or on a street/highway (21.3%). Homicides were precipitated
      primarily by arguments (41.4%) and interpersonal conflicts (18.4%) or in
      conjunction with another crime (30.2%). Other manners of death and special
      situations or populations also are highlighted in this report. INTERPRETATION:
      This report provides a detailed summary of data from NVDRS for 2008. The results
      indicate that violent deaths resulting from self-inflicted or interpersonal
      violence disproportionately affected adults aged <55 years, males, and certain
      minority populations. For homicides and suicides, relationship problems,
      interpersonal conflicts, mental health problems, and recent crises were among the
      primary precipitating factors. Because additional information might be reported
      subsequently as participating states update their findings, the data provided in
      this report are preliminary. PUBLIC HEALTH ACTION: For the occurrence of violent
      deaths in the United States to be better understood and ultimately prevented,
      accurate, timely, and comprehensive surveillance data are necessary. NVDRS data
      can be used to monitor the occurrence of violence-related fatal injuries and
      assist public health authorities in the development, implementation, and
      evaluation of programs and policies to reduce and prevent violent deaths at the
      national, state, and local levels. The continued development and expansion of
      NVDRS is essential to CDC's efforts to reduce the personal, familial, and
      societal costs of violence. Further efforts are needed to increase the number of
      states participating in NVDRS, with an ultimate goal of full national
      representation.

PMID- 21866089
TI  - Markers of inflammation predict the long-term risk of developing chronic kidney
      disease: a population-based cohort study.
AB  - In animal models, inflammatory processes have been shown to have an important
      role in the development of kidney disease. In humans, however, the independent
      relation between markers of inflammation and the risk of chronic kidney disease
      (CKD) is not known. To clarify this, we examined the relationship of several
      inflammatory biomarker levels (high-sensitivity C-reactive protein, tumor
      necrosis factor-alpha receptor 2, white blood cell count, and interleukin-6) with
      the risk of developing CKD in a population-based cohort of up to 4926 patients
      with 15 years of follow-up. In cross-sectional analyses, we found that all these
      inflammation markers were positively associated with the outcome of interest,
      prevalent CKD. However, in longitudinal analyses examining the risk of developing
      incident CKD among those who were CKD-free at baseline, only tumor necrosis
      factor-alpha receptor 2, white blood cell count, and interleukin-6 levels (hazard
      ratios comparing highest with the lowest tertile of 2.10, 1.90, and 1.45,
      respectively), and not C-reactive protein (hazard ratio 1.09), were positively
      associated with incident CKD. Thus, elevations of most markers of inflammation
      predict the risk of developing CKD. Each marker should be independently verified.

PMID- 21866090
TI  - Inverted formin 2 mutations with variable expression in patients with sporadic
      and hereditary focal and segmental glomerulosclerosis.
AB  - Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage
      kidney disease. Recent advances in molecular genetics show that defects in the
      podocyte play a major role in its pathogenesis and mutations in inverted formin 2
      (INF2) cause autosomal dominant FSGS. In order to delineate the role of INF2
      mutations in familial and sporadic FSGS, we sought to identify variants in a
      large cohort of patients with FSGS. A secondary objective was to define an
      approach for genetic screening in families with autosomal dominant disease. A
      total of 248 individuals were identified with FSGS, of whom 31 had idiopathic
      disease. The remaining patients clustered into 64 families encompassing 15 from
      autosomal recessive and 49 from autosomal dominant kindreds. There were missense
      mutations in 8 of the 49 families with autosomal dominant disease. Three of the
      detected variants were novel and all mutations were confined to exon 4 of INF2, a
      regulatory region responsible for 90% of all changes reported in FSGS due to INF2
      mutations. Thus, in our series, INF2 mutations were responsible for 16% of all
      cases of autosomal dominant FSGS, with these mutations clustered in exon 4.
      Hence, screening for these mutations may represent a rapid, non-invasive and cost
      effective method for the diagnosis of autosomal dominant FSGS.

PMID- 21866091
TI  - Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1
      and soluble CD89-IgA and IgG-IgA complexes: common mechanisms for distinct
      diseases.
AB  - Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA
      deposits with possible development of secondary IgA nephropathy (IgAN). Since
      little is known about circulating immune complexes in cases of secondary IgAN, we
      analyzed IgA-associated parameters in the serum of 32 patients with compensated
      or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation
      of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1,
      were detected in the serum of patients with advanced alcoholic cirrhosis.
      Moreover, aberrant IgA1 formed complexes with IgG and soluble CD89 in serum of
      patients with advanced alcoholic cirrhosis, similar to those found in primary
      IgAN. The IgA1 of alcoholic cirrhosis, however, had a modified N-glycosylation,
      not found in primary IgAN. In patients with alcoholic cirrhosis and IgAN, IgA
      deposits were associated with CD71 overexpression in mesangial areas, suggesting
      that CD71 might be involved in deposit formation. Although the IgA1 found in
      alcoholic cirrhosis bound more extensively to human mesangial cells than control
      IgA1, they differ from primary IgAN by not inducing mesangial cell proliferation.
      Thus, abnormally glycosylated IgA1 and soluble CD89-IgA and IgA-IgG complexes,
      features of primary IgAN, are also present in alcoholic cirrhosis. Hence, common
      mechanisms appear to be shared by diseases of distinct origins, indicating that
      common environmental factors may influence the development of IgAN.

PMID- 21866092
TI  - Hyperoxaluria: a gut-kidney axis?
AB  - Hyperoxaluria leads to urinary calcium oxalate (CaOx) supersaturation, resulting
      in the formation and retention of CaOx crystals in renal tissue. CaOx crystals
      may contribute to the formation of diffuse renal calcifications
      (nephrocalcinosis) or stones (nephrolithiasis). When the innate renal defense
      mechanisms are suppressed, injury and progressive inflammation caused by these
      CaOx crystals, together with secondary complications such as tubular obstruction,
      may lead to decreased renal function and in severe cases to end-stage renal
      failure. For decades, research on nephrocalcinosis and nephrolithiasis mainly
      focused on both the physicochemistry of crystal formation and the cell biology of
      crystal retention. Although both have been characterized quite well, the
      mechanisms involved in establishing urinary supersaturation in vivo are
      insufficiently understood, particularly with respect to oxalate. Therefore,
      current therapeutic strategies often fail in their compliance or effectiveness,
      and CaOx stone recurrence is still common. As the etiology of hyperoxaluria is
      diverse, a good understanding of how oxalate is absorbed and transported
      throughout the body, together with a better insight in the regulatory mechanisms,
      is crucial in the setting of future treatment strategies of this disorder. In
      this review, the currently known mechanisms of oxalate handling in relevant
      organs will be discussed in relation to the different etiologies of
      hyperoxaluria. Furthermore, future directions in the treatment of hyperoxaluria
      will be covered.

PMID- 21866093
TI  - Increased influx of myeloid dendritic cells during acute rejection is associated
      with interstitial fibrosis and tubular atrophy and predicts poor outcome.
AB  - Dendritic cells are key players in renal allograft rejection and have been
      identified as an intrinsic part of the kidney. Here we quantified and phenotyped
      the dendritic cell populations in well-defined biopsies of 102 patients with
      acute renal allograft rejection in comparison with 78 available pretransplant
      biopsies. There was a strong increase in BDCA-1(+) and DC-SIGN(+) myeloid, BDCA
      2(+) plasmacytoid, and DC-LAMP(+) mature dendritic cells in rejection biopsies
      compared with the corresponding pretransplant tissue. Mature dendritic cells were
      mostly found in clusters of lymphoid infiltrate and showed a strong correlation
      with the Banff infiltrate score. The presence of both myeloid and plasmacytoid
      dendritic cell subsets in the kidney during acute rejection correlated with
      interstitial fibrosis and tubular atrophy. Importantly, the myeloid dendritic
      cell density at the time of acute rejection was an independent risk factor for
      loss of renal function after the first year. Thus, acute renal allograft
      rejection is characterized by an influx of myeloid and plasmacytoid dendritic
      cells, strongly associated with local damage in the graft. Hence, the density of
      myeloid dendritic cells during acute rejection could be an important risk factor
      for the long-term development of chronic changes and loss of graft function.

PMID- 21866094
TI  - Induction of progressive glomerulonephritis by podocyte-specific overexpression
      of platelet-derived growth factor-D.
AB  - Platelet-derived growth factor-D (PDGF-D), normally expressed in podocytes,
      mediates mesangial cell proliferation in vivo. To study this further, we created
      transgenic mice with podocyte-specific overexpression of PDGF-D. Hemizygous mice
      were grossly indistinguishable from wild-type littermates through 11 months of
      age; however, hemizygous mice older than 4 weeks commonly exhibited increased
      cell proliferation within the glomerular tuft. Many hemizygous mice also
      developed widespread segmental glomerulosclerosis and focal extracapillary
      proliferation with fibrin/fibrinogen deposition, extensive tubulointerstitial
      damage, proteinuria, and renal insufficiency. Electron microscopy found focal
      foot process effacement. Renal mRNA expression of podocin and nephrin, as well as
      the number of glomerular WT-1-positive cells, were significantly reduced in
      hemizygous compared to wild-type mice, indicating loss and/or dedifferentation of
      podocytes. PDGF-A, -B, and both PDGF receptor chain mRNAs, fibronectin, type IV
      collagen, RANTES, MCP-1, and CCR-2 mRNAs were all increased in the renal cortex
      of PDGF-D transgenic mice. Only 8.5% of newborn mice were homozygous
      overexpressors exhibiting a mortality rate of 37% at 4 weeks. Thus, podocyte
      specific overexpression of PDGF-D caused mesangioproliferative disease,
      glomerulosclerosis, and crescentic glomerulonephritis. Hence, podocyte-specific
      growth factor overexpression can induce paracrine mesangial cell proliferation
      upstream of the filtration flow.

PMID- 21866096
TI  - First-time-in-human study with GSK1018921, a selective GlyT1 inhibitor:
      relationship between exposure and dizziness.
AB  - The pharmacokinetics (PK), safety, and tolerability of GSK1018921, a glycine
      transporter 1 (GlyT-1) inhibitor, were assessed in this first-time-in-human
      (FTIH) study. Single oral doses ranging from 0.5 to 280 mg and placebo were
      administered to 25 healthy subjects in a five-period, two-cohort, crossover
      study. GSK1018921 showed dose-proportional PK with a terminal half-life of ~17 h.
      The subjects reported dizziness with a dose-dependent frequency of 22-88% at
      doses of 70-280 mg. The time course of the dizziness paralleled the PK of the
      drug, with peak response at 2 h after the dose, consistent with time to maximum
      plasma concentration (T(max)). The dizziness was resolved by 10-12 h in all
      subjects. A Markov-chain logistic regression model was implemented in NONMEM to
      determine the probability of developing dizziness as a function of the plasma
      concentration of the compound. Frequency, onset (<1 h), and offset (4 h) were
      well described by the model. Exposure resulting in 80% receptor occupancy is
      predicted to be well tolerated.

PMID- 21866095
TI  - Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies.
AB  - Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, is the
      most frequent genetic cause for end-stage renal failure in the first three
      decades of life. Mutations in 13 genes (NPHP1-NPHP11, AHI1, and CC2D2A) cause
      NPHP with ubiquitous expression of the corresponding proteins consistent with the
      multiorgan involvement of NPHP-related diseases. The genotype-phenotype
      correlation in these ciliopathies can be explained by gene locus heterogeneity,
      allelism, and the impact of modifier genes. In some NPHP-related ciliopathies,
      the nature of the recessive mutations determines disease severity. In order to
      define the genotype-phenotype correlation more clearly, we evaluated a worldwide
      cohort of 440 patients from 365 families with NPHP-related ciliopathies, in whom
      both disease-causing alleles were identified. The phenotypes were ranked in the
      order of severity from degenerative to degenerative/dysplastic to dysplastic. A
      genotype of two null alleles caused a range of phenotypes, with an increasing
      order of severity of NPHP1, NPHP3, NPHP4, NPHP5, NPHP2, NPHP10, NPHP6, to AHI1.
      Only NPHP6 showed allelic influences on the phenotypes; the presence of two null
      mutations caused dysplastic phenotypes, whereas at least one missense allele
      rescued it to a milder degenerative phenotype. We also found nine novel mutations
      in the NPHP genes. Thus, our studies have important implications for genetic
      counseling and planning of renal replacement therapy.

PMID- 21866098
TI  - Genotype-based quantitative prediction of drug exposure for drugs metabolized by
      CYP2D6.
AB  - We propose a framework to enable quantitative prediction of the impact of CYP2D6
      polymorphisms on drug exposure. It relies mostly on in vivo data and uses two
      characteristic parameters: one for the drug and the other for the genotype. The
      metric of interest is the ratio of drug area under the curve (AUC) in patients
      with mutant genotype to the AUC in patients with wild-type genotype. Any
      combination of alleles, as well as duplications, may be accommodated in the
      framework. Estimates of the characteristic parameters were obtained by orthogonal
      regression for 40 drugs and five classes of genotypes, respectively, including
      poor, intermediate, and ultrarapid metabolizers (PMs, IMs, and UMs). The mean
      prediction error of AUC ratios was -0.05, and the mean prediction absolute error
      was 0.20. An external validation was also carried out. The model may be used to
      predict the variations in exposure induced by all drug-genotype combinations. An
      application of this model to a rare combination of alleles (*4*10) is described.

PMID- 21866097
TI  - Gene therapy targets in heart failure: the path to translation.
AB  - Heart failure (HF) is the common end point of cardiac diseases. Despite the
      optimization of therapeutic strategies and the consequent overall reduction in HF
      related mortality, the key underlying intracellular signal transduction
      abnormalities have not been addressed directly. In this regard, the gaps in
      modern HF therapy include derangement of beta-adrenergic receptor (beta-AR)
      signaling, Ca(2+) disbalances, cardiac myocyte death, diastolic dysfunction, and
      monogenetic cardiomyopathies. In this review we discuss the potential of gene
      therapy to fill these gaps and rectify abnormalities in intracellular signaling.
      We also examine current vector technology and currently available vector-delivery
      strategies, and we delineate promising gene therapy structures. Finally, we
      analyze potential limitations related to the transfer of successful preclinical
      gene therapy approaches to HF treatment in the clinic, as well as impending
      strategies aimed at overcoming these limitations.

PMID- 21866099
TI  - Evaluation of drug interactions in a large sample of psychiatric inpatients: a
      data interface for mass analysis with clinical decision support software.
AB  - In order to improve medication safety, more epidemiological data on the
      prevalence and clinical relevance of drug interactions are required. We developed
      an interface for mass analysis using the Clinical Decision Support Software
      (CDSS) MediQ and a multidimensional classification (Zurich Interaction System
      (ZHIAS)) incorporating the Operational Classification of Drug Interactions
      (ORCA). These were applied to 359,207 cross-sectional prescriptions from 84,607
      psychiatric inpatients collected through the international AMSP program. MediQ
      issued 2,308 "high" and 71,112 "average" danger interaction alerts. Among these,
      after ORCA reclassification, there were 151 contraindicated and 4,099
      provisionally contraindicated prescriptions. The ZHIAS provided further detailed
      categorical information on recommended management and specific increased risks
      (QTc prolongation being the most frequent one) associated with interactions. We
      developed a highly efficient solution for the identification and classification
      of drug interactions in large prescription data sets; this solution may help to
      reduce the frequency of overalerting and improve acceptance of the efficacy of
      CDSS in reducing the occurrence of potentially harmful drug interactions.

PMID- 21866100
TI  - Three classical Cepheid variable stars in the nuclear bulge of the Milky Way.
AB  - The nuclear bulge is a region with a radius of about 200 parsecs around the
      centre of the Milky Way. It contains stars with ages ranging from a few million
      years to over a billion years, yet its star-formation history and the triggering
      process for star formation remain to be resolved. Recently, episodic star
      formation, powered by changes in the gas content, has been suggested. Classical
      Cepheid variable stars have pulsation periods that decrease with increasing age,
      so it is possible to probe the star-formation history on the basis of the
      distribution of their periods. Here we report the presence of three classical
      Cepheids in the nuclear bulge with pulsation periods of approximately 20 days,
      within 40 parsecs (projected distance) of the central black hole. No Cepheids
      with longer or shorter periods were found. We infer that there was a period about
      25 million years ago, and possibly lasting until recently, in which star
      formation increased relative to the period of 30-70 million years ago.

PMID- 21866101
TI  - Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus
      infection.
AB  - Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks
      of zoonotic infection in Africa. The clinical symptoms are manifestations of the
      massive production of pro-inflammatory cytokines in response to infection and in
      many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of
      transmission, rapid progression of disease, high mortality and lack of effective
      vaccine or therapy have created a high level of public concern about EboV. Here
      we report the identification of a novel benzylpiperazine adamantane diamide
      derived compound that inhibits EboV infection. Using mutant cell lines and
      informative derivatives of the lead compound, we show that the target of the
      inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that
      NPC1 is essential for infection, that it binds to the virus glycoprotein (GP),
      and that antiviral compounds interfere with GP binding to NPC1. Combined with the
      results of previous studies of GP structure and function, our findings support a
      model of EboV infection in which cleavage of the GP1 subunit by endosomal
      cathepsin proteases removes heavily glycosylated domains to expose the amino
      terminal domain, which is a ligand for NPC1 and regulates membrane fusion by the
      GP2 subunit. Thus, NPC1 is essential for EboV entry and a target for antiviral
      therapy.

PMID- 21866102
TI  - Evidence for several waves of global transmission in the seventh cholera
      pandemic.
AB  - Vibrio cholerae is a globally important pathogen that is endemic in many areas of
      the world and causes 3-5 million reported cases of cholera every year.
      Historically, there have been seven acknowledged cholera pandemics; recent
      outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic.
      Only isolates in serogroup O1 (consisting of two biotypes known as 'classical'
      and 'El Tor') and the derivative O139 can cause epidemic cholera. It is believed
      that the first six cholera pandemics were caused by the classical biotype, but El
      Tor has subsequently spread globally and replaced the classical biotype in the
      current pandemic. Detailed molecular epidemiological mapping of cholera has been
      compromised by a reliance on sub-genomic regions such as mobile elements to infer
      relationships, making El Tor isolates associated with the seventh pandemic seem
      superficially diverse. To understand the underlying phylogeny of the lineage
      responsible for the current pandemic, we identified high-resolution markers
      (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally
      and temporally representative V. cholerae isolates. Using this phylogeny, we show
      here that the seventh pandemic has spread from the Bay of Bengal in at least
      three independent but overlapping waves with a common ancestor in the 1950s, and
      identify several transcontinental transmission events. Additionally, we show how
      the acquisition of the SXT family of antibiotic resistance elements has shaped
      pandemic spread, and show that this family was first acquired at least ten years
      before its discovery in V. cholerae.

PMID- 21866106
TI  - Why does the United States need a national center for new cures?

PMID- 21866104
TI  - The mechanism of membrane-associated steps in tail-anchored protein insertion.
AB  - Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are
      chaperoned by cytosolic targeting factors that deliver them to a membrane
      receptor for insertion. Although a basic framework for TA protein recognition is
      now emerging, the decisive targeting and membrane insertion steps are not
      understood. Here we reconstitute the TA protein insertion cycle with purified
      components, present crystal structures of key complexes between these components
      and perform mutational analyses based on the structures. We show that a committed
      targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is
      initially recruited to the membrane through an interaction with Get2. Once the
      targeting complex has been recruited, Get1 interacts with Get3 to drive TA
      protein release in an ATPase-dependent reaction. After releasing its TA protein
      cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP
      binding. This work provides a detailed structural and mechanistic framework for
      the minimal TA protein insertion cycle.

PMID- 21866107
TI  - The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac
      hypertrophy in mice.
AB  - Pirfenidone (5-methyl-1-phenyl-2-[(1)H]-pyridone) is an effective drug for
      idiopathic interstitial pneumonia that can prevent and reverse tissue fibrosis in
      several organs. Therefore, we investigated whether pirfenidone has a potential
      role in preventing angiotensin II (Ang II)-induced cardiac hypertrophy. A cardiac
      hypertrophic mouse model was created using an Ang II infusion (200 ng kg(-1) min(
      1)) in wild-type mice for 2 weeks. Mice were divided into the following three
      groups: a saline-infused (control) group, an Ang II infusion (vehicle) group and
      an Ang II infusion+pirfenidone-treated (PFD) group, which received pirfenidone
      (300 mg kg(-1) per day) by gastric gavage during the Ang II infusion. At 2 weeks,
      we assessed hemodynamics and cardiac function and investigated tissue fibrosis of
      the myocardium histologically and genetically. Blood pressure in the vehicle
      group was significantly increased compared to the control group. Although blood
      pressure was not different between the vehicle and PFD groups, heart weight was
      significantly decreased in the PFD group. Echocardiography revealed that left
      ventricular hypertrophy was significantly increased in the vehicle group vs. the
      control group. Interestingly, pirfenidone significantly inhibited this effect.
      Continuous infusion of Ang II increased the perivascular and interstitial tissue
      fibrosis, and pirfenidone inhibited these fibrotic changes. Pirfenidone also
      inhibited Ang II-induced hypertrophy. In the vehicle group, the mRNA expressions
      of atrial natriuretic peptide, brain natriuretic peptide and transforming growth
      factor-beta1 were increased, which was significantly inhibited by pirfenidone.
      Furthermore, the expression of mineralocorticoid receptors was attenuated by
      pirfenidone. These results indicate that pirfenidone might be effective as an
      antifibrotic drug in the treatment of cardiac hypertrophy induced by
      hypertension.

PMID- 21866103
TI  - Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.
AB  - Infections by the Ebola and Marburg filoviruses cause a rapidly fatal
      haemorrhagic fever in humans for which no approved antivirals are available.
      Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches
      viral particles to the cell surface, delivers them to endosomes and catalyses
      fusion between viral and endosomal membranes. Additional host factors in the
      endosomal compartment are probably required for viral membrane fusion; however,
      despite considerable efforts, these critical host factors have defied molecular
      identification. Here we describe a genome-wide haploid genetic screen in human
      cells to identify host factors required for Ebola virus entry. Our screen
      uncovered 67 mutations disrupting all six members of the homotypic fusion and
      vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved
      in the fusion of endosomes to lysosomes, and 39 independent mutations that
      disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1
      (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary
      fibroblasts derived from human Niemann-Pick type C1 disease patients, are
      resistant to infection by Ebola virus and Marburg virus, but remain fully
      susceptible to a suite of unrelated viruses. We show that membrane fusion
      mediated by filovirus glycoproteins and viral escape from the vesicular
      compartment require the NPC1 protein, independent of its known function in
      cholesterol transport. Our findings uncover unique features of the entry pathway
      used by filoviruses and indicate potential antiviral strategies to combat these
      deadly agents.

PMID- 21866108
TI  - The effect of treatment on monocyte and lymphocyte cytokine release in patients
      with aldosteronoma.

PMID- 21866109
TI  - Day-by-day home-measured blood pressure variability: another important factor in
      hypertension with diabetic nephropathy?

PMID- 21866110
TI  - Tandem configurations of variably duplicated segments of 22q11.2 confirmed by
      fiber-FISH analysis.
AB  - 22q11.2 duplication syndrome has recently been established as a new syndrome
      manifesting broad clinical phenotypes including mental retardation. It is
      reciprocal to DiGeorge (DGS)/velo-cardio-facial syndrome (VCFS), in which the
      same portion of the chromosome is hemizygously deleted. Deletions and
      duplications of the 22q11.2 region are facilitated by the low-copy repeats (LCRs)
      flanking this region. In this study, we aimed to identify the directions of the
      duplicated segments of 22q11.2 to better understand the mechanism of chromosomal
      duplication. To achieve this aim, we accumulated samples from four patients with
      22q11.2 duplications. One of the patients had an atypically small (741 kb)
      duplication of 22q11.2. The centromeric end of the breakpoint was on LCR22A, but
      the telomeric end was between LCR22A and B. Therefore, the duplicated segment did
      not include T-box 1 gene (TBX1), the gene primarily responsible for the DGS/VCFS.
      As this duplication was shared by the patient's healthy mother, this appears to
      be a benign copy-number variation rather than a disease-causing alteration. The
      other three patients showed 3.0 or 4.0 Mb duplications flanked by LCRs. The
      directions of the duplicated segments were investigated by fiber-fluorescence in
      situ hybridization analysis. All samples showed tandem configurations. These
      results support the hypothesized mechanism of non-allelic homologous
      recombination with flanking LCRs and add additional evidence that many
      interstitial duplications are aligned as tandem configurations.

PMID- 21866111
TI  - Gene expression analysis in lymphoblastoid cells as a potential biomarker of
      bipolar disorder.
AB  - Although there is an urgent need for biological diagnosis of bipolar disorder
      (BD), there have been no established biomarkers. Gene expression analysis in
      lymphoblastoid cells (LCLs) would be a promising candidate for biomarkers. In
      this study, 17 candidate genes were measured in the LCLs of patients with BD.
      Using the data of the first set of samples (13 patients with bipolar I disorder
      and 21 controls), three genes, ANK3, RASGRP1 and POLG1, were selected by the
      logistic regression analysis with a stepwise method. Using the discriminant
      function generated by this analysis, the first sample was discriminated with the
      sensitivity of 76% and specificity of 85%. By applying the same function to the
      second sample set (18 patients with bipolar I and 37 controls), bipolar I
      disorder could be discriminated from the controls with the sensitivity of 44% and
      specificity of 81% (chi(2)=3.97, P=0.046). This study was the first to suggest a
      possible role of gene expression analysis of ANK3, RASGRP1 and POLG1 in the LCLs
      as potential biomarkers of BD.

PMID- 21866112
TI  - Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate
      in a Malay population.
AB  - Oral clefts are clinically and genetically heterogeneous disorders that are
      influenced by both genetic and environmental factors. The present family-based
      association study investigated the role of the MSX1 and TGFB3 genes in the
      etiology of non-syndromic oral cleft in a Malay population. No transmission
      distortion was found in the transmission disequilibrium analysis for either MSX1
      CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess
      maternal transmission. In sequencing the MSX1 coding regions in 124 patients with
      oral cleft, five variants were found, including three known variants (A34G, G110G
      and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants
      were not observed in 200 control chromosomes, whereas G267A was found in one
      control sample, indicating a very rare polymorphic variant. Furthermore, the
      G110G variant displayed a significant association between patients with non
      syndromic cleft lip, with or without cleft palate, and normal controls (P=0.001,
      odds ratio=2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic
      variants may contribute, along with other genetic and environmental factors, to
      this condition.

PMID- 21866113
TI  - The generation of mitochondrial DNA large-scale deletions in human cells.
AB  - Large-scale deletions of human mitochondrial DNA (mtDNA) are a common cause of
      mitochondrial diseases. In order to prevent and treat these mitochondrial
      diseases, it is important and necessary to understand the mechanisms behind the
      generation of these deletions. Generally, there exist three kinds of large-scale
      deletions: deletions almost occur within two direct repeats with identical
      sequences (class I deletions), deletions are flanked by imperfect repeats (class
      II deletions) and by no direct repeats (class III deletions). Two major
      hypotheses are suggested to generate these deletions: replication for class I/II
      deletions through slipped mispairing between two repeats, and repair mainly for
      class II/III deletions mediated by mtDNA double-strand breaks. It seems possible
      that these two mechanisms work together as a powerful and complementary system to
      compensate for their defects in the generation of all these deletions, not
      respectively.

PMID- 21866114
TI  - A eulogy to the late Professor Eiji Inouye.

PMID- 21866116
TI  - Go with the flow.

PMID- 21866117
TI  - Spoils of war.

PMID- 21866115
TI  - The rs5743836 polymorphism in TLR9 confers a population-based increased risk of
      non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) has been associated with immunological defects,
      chronic inflammatory and autoimmune conditions. Given the link between immune
      dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been
      regarded as potential predictive factors of susceptibility to NHL. Adequate anti
      tumoral responses are known to depend on TLR9 function, such that the use of its
      synthetic ligand is being targeted as a therapeutic strategy. We investigated the
      association between the functional rs5743836 polymorphism in the TLR9 promoter
      and risk for B-cell NHL and its major subtypes in three independent case-control
      association studies from Portugal (1160 controls, 797 patients), Italy (468
      controls, 494 patients) and the US (972 controls, 868 patients). We found that
      the rs5743836 polymorphism was significantly overtransmitted in both Portuguese
      (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the
      US cohort of NHL patients. Moreover, the increased transcriptional activity of
      TLR9 in mononuclear cells from patients harboring rs5743836 further supports a
      functional effect of this polymorphism on NHL susceptibility in a population
      dependent manner.

PMID- 21866130
TI  - NASA to share telescope cost.

PMID- 21866118
TI  - Stand up against the anti-technology terrorists.

PMID- 21866131
TI  - Toxic antibodies blitz tumours.

PMID- 21866132
TI  - Growth of egg freezing blurs 'experimental' label.

PMID- 21866133
TI  - Thrift in store for US research.

PMID- 21866134
TI  - Italy chooses new brooms to clean up science institutes.

PMID- 21866135
TI  - Cell signalling: It's all about the structure.

PMID- 21866136
TI  - Earthquakes from the ocean: Danger zones.

PMID- 21866137
TI  - Antibiotic overuse: Stop the killing of beneficial bacteria.

PMID- 21866142
TI  - Research funding: Learn from Ireland's knowledge economy.

PMID- 21866143
TI  - Conservation: Invest in a DNA bank for all species.

PMID- 21866144
TI  - Risk factors: Nanomaterials should be defined.

PMID- 21866145
TI  - Downloads: Stats for papers let authors track impact.

PMID- 21866146
TI  - Jonathan Widom (1955-2011).

PMID- 21866147
TI  - Forum. Chemical engineering: Fuel for debate.

PMID- 21866148
TI  - Nanotechnology: Smart connections.

PMID- 21866149
TI  - Astrophysics: The awakening of a cosmic monster.

PMID- 21866150
TI  - Environmental science: Climate for conflict.

PMID- 21866151
TI  - Dengue fever: Mosquitoes attacked from within.

PMID- 21866153
TI  - Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit
      tip.
AB  - The regrowth of amputated limbs and the distal tips of digits represent models of
      tissue regeneration in amphibians, fish and mice. For decades it had been assumed
      that limb regeneration derived from the blastema, an undifferentiated pluripotent
      cell population thought to be derived from mature cells via dedifferentiation.
      Here we show that a wide range of tissue stem/progenitor cells contribute towards
      the restoration of the mouse distal digit. Genetic fate mapping and clonal
      analysis of individual cells revealed that these stem cells are lineage
      restricted, mimicking digit growth during development. Transplantation of cyan
      fluorescent-protein-expressing haematopoietic stem cells, and parabiosis between
      genetically marked mice, confirmed that the stem/progenitor cells are tissue
      resident, including the cells involved in angiogenesis. These results, combined
      with those from appendage regeneration in other vertebrate subphyla, collectively
      demonstrate that tissue stem cells rather than pluripotent blastema cells are an
      evolutionarily conserved cellular mode for limb regeneration after amputation.

PMID- 21866154
TI  - Relativistic jet activity from the tidal disruption of a star by a massive black
      hole.
AB  - Supermassive black holes have powerful gravitational fields with strong gradients
      that can destroy stars that get too close, producing a bright flare in
      ultraviolet and X-ray spectral regions from stellar debris that forms an
      accretion disk around the black hole. The aftermath of this process may have been
      seen several times over the past two decades in the form of sparsely sampled,
      slowly fading emission from distant galaxies, but the onset of the stellar
      disruption event has not hitherto been observed. Here we report observations of a
      bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This
      source increased in brightness in the X-ray band by a factor of at least 10,000
      since 1990 and by a factor of at least 100 since early 2010. We conclude that we
      have captured the onset of relativistic jet activity from a supermassive black
      hole. A companion paper comes to similar conclusions on the basis of radio
      observations. This event is probably due to the tidal disruption of a star
      falling into a supermassive black hole, but the detailed behaviour differs from
      current theoretical models of such events.

PMID- 21866155
TI  - Birth of a relativistic outflow in the unusual gamma-ray transient Swift
      J164449.3+573451.
AB  - Active galactic nuclei, which are powered by long-term accretion onto central
      supermassive black holes, produce relativistic jets with lifetimes of at least
      one million years, and the observation of the birth of such a jet is therefore
      unlikely. Transient accretion onto a supermassive black hole, for example through
      the tidal disruption of a stray star, thus offers a rare opportunity to study the
      birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift
      J164449.3+573451) was found, potentially representing such an accretion event.
      Here we report observations spanning centimetre to millimetre wavelengths and
      covering the first month of evolution of a luminous radio transient associated
      with Swift J164449.3+573451. The radio transient coincides with the nucleus of an
      inactive galaxy. We conclude that we are seeing a newly formed relativistic
      outflow, launched by transient accretion onto a million-solar-mass black hole. A
      relativistic outflow is not predicted in this situation, but we show that the
      tidal disruption of a star naturally explains the observed high-energy properties
      and radio luminosity and the inferred rate of such events. The weaker beaming in
      the radio-frequency spectrum relative to gamma-rays or X-rays suggests that radio
      searches may uncover similar events out to redshifts of z ~ 6.

PMID- 21866156
TI  - Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol
      nucleation.
AB  - Atmospheric aerosols exert an important influence on climate through their
      effects on stratiform cloud albedo and lifetime and the invigoration of
      convective storms. Model calculations suggest that almost half of the global
      cloud condensation nuclei in the atmospheric boundary layer may originate from
      the nucleation of aerosols from trace condensable vapours, although the
      sensitivity of the number of cloud condensation nuclei to changes of nucleation
      rate may be small. Despite extensive research, fundamental questions remain about
      the nucleation rate of sulphuric acid particles and the mechanisms responsible,
      including the roles of galactic cosmic rays and other chemical species such as
      ammonia. Here we present the first results from the CLOUD experiment at CERN. We
      find that atmospherically relevant ammonia mixing ratios of 100 parts per
      trillion by volume, or less, increase the nucleation rate of sulphuric acid
      particles more than 100-1,000-fold. Time-resolved molecular measurements reveal
      that nucleation proceeds by a base-stabilization mechanism involving the stepwise
      accretion of ammonia molecules. Ions increase the nucleation rate by an
      additional factor of between two and more than ten at ground-level galactic
      cosmic-ray intensities, provided that the nucleation rate lies below the limiting
      ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)
      H(2)O can occur in the mid-troposphere but is negligible in the boundary layer.
      However, even with the large enhancements in rate due to ammonia and ions,
      atmospheric concentrations of ammonia and sulphuric acid are insufficient to
      account for observed boundary-layer nucleation.

PMID- 21866157
TI  - Civil conflicts are associated with the global climate.
AB  - It has been proposed that changes in global climate have been responsible for
      episodes of widespread violence and even the collapse of civilizations. Yet
      previous studies have not shown that violence can be attributed to the global
      climate, only that random weather events might be correlated with conflict in
      some cases. Here we directly associate planetary-scale climate changes with
      global patterns of civil conflict by examining the dominant interannual mode of
      the modern climate, the El Nino/Southern Oscillation (ENSO). Historians have
      argued that ENSO may have driven global patterns of civil conflict in the distant
      past, a hypothesis that we extend to the modern era and test quantitatively.
      Using data from 1950 to 2004, we show that the probability of new civil conflicts
      arising throughout the tropics doubles during El Nino years relative to La Nina
      years. This result, which indicates that ENSO may have had a role in 21% of all
      civil conflicts since 1950, is the first demonstration that the stability of
      modern societies relates strongly to the global climate.

PMID- 21866158
TI  - A Jurassic eutherian mammal and divergence of marsupials and placentals.
AB  - Placentals are the most abundant mammals that have diversified into every niche
      for vertebrates and dominated the world's terrestrial biotas in the Cenozoic. A
      critical event in mammalian history is the divergence of eutherians, the clade
      inclusive of all living placentals, from the metatherian-marsupial clade. Here we
      report the discovery of a new eutherian of 160 Myr from the Jurassic of China,
      which extends the first appearance of the eutherian-placental clade by about 35
      Myr from the previous record, reducing and resolving a discrepancy between the
      previous fossil record and the molecular estimate for the placental-marsupial
      divergence. This mammal has scansorial forelimb features, and provides the
      ancestral condition for dental and other anatomical features of eutherians.

PMID- 21866159
TI  - The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti
      populations.
AB  - Dengue fever is the most important mosquito-borne viral disease of humans with
      more than 50 million cases estimated annually in more than 100 countries.
      Disturbingly, the geographic range of dengue is currently expanding and the
      severity of outbreaks is increasing. Control options for dengue are very limited
      and currently focus on reducing population abundance of the major mosquito
      vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in
      tropical communities and there is an urgent need for effective alternatives. It
      has been proposed that endosymbiotic bacterial Wolbachia infections of insects
      might be used in novel strategies for dengue control. For example, the wMelPop
      CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in
      stably transinfected lines. This life-shortening phenotype was predicted to
      reduce the potential for dengue transmission. The recent discovery that several
      Wolbachia infections, including wMelPop-CLA, can also directly influence the
      susceptibility of insects to infection with a range of insect and human pathogens
      has markedly changed the potential for Wolbachia infections to control human
      diseases. Here we describe the successful transinfection of A. aegypti with the
      avirulent wMel strain of Wolbachia, which induces the reproductive phenotype
      cytoplasmic incompatibility with minimal apparent fitness costs and high maternal
      transmission, providing optimal phenotypic effects for invasion. Under semi-field
      conditions, the wMel strain increased from an initial starting frequency of 0.65
      to near fixation within a few generations, invading A. aegypti populations at an
      accelerated rate relative to trials with the wMelPop-CLA strain. We also show
      that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV
      2) in A. aegypti, forming the basis of a practical approach to dengue
      suppression.

PMID- 21866160
TI  - Successful establishment of Wolbachia in Aedes populations to suppress dengue
      transmission.
AB  - Genetic manipulations of insect populations for pest control have been advocated
      for some time, but there are few cases where manipulated individuals have been
      released in the field and no cases where they have successfully invaded target
      populations. Population transformation using the intracellular bacterium
      Wolbachia is particularly attractive because this maternally-inherited agent
      provides a powerful mechanism to invade natural populations through cytoplasmic
      incompatibility. When Wolbachia are introduced into mosquitoes, they interfere
      with pathogen transmission and influence key life history traits such as
      lifespan. Here we describe how the wMel Wolbachia infection, introduced into the
      dengue vector Aedes aegypti from Drosophila melanogaster, successfully invaded
      two natural A. aegypti populations in Australia, reaching near-fixation in a few
      months following releases of wMel-infected A. aegypti adults. Models with
      plausible parameter values indicate that Wolbachia-infected mosquitoes suffered
      relatively small fitness costs, leading to an unstable equilibrium frequency <30%
      that must be exceeded for invasion. These findings demonstrate that Wolbachia
      based strategies can be deployed as a practical approach to dengue suppression
      with potential for area-wide implementation.

PMID- 21866164
TI  - Relation of central and brachial blood pressure to left ventricular hypertrophy.
      The Czech Post-MONICA Study.
AB  - Central blood pressure (BP) has been shown to be a better predictor of target
      organ damage and cardiovascular events than brachial BP. Whether central BP is a
      better predictor of left ventricular hypertrophy (LVH) determined by
      electrocardiography (ECG) is not known. Radial applanation tonometry and ECG were
      performed in 728 subjects from the Czech Post-MONICA Study (a randomly selected
      1% population sample). LVH was determined using the Sokolow-Lyon index and
      Cornell product; central pressure was derived from radial pulse. Of 657 subjects
      included in the analysis, 17 (9.4%) below 45 years and 43 (9%) over 45 years had
      LVH. In multiple linear regression analysis, the Sokolow-Lyon index in younger
      individuals was only associated with male sex and low BMI, with no association
      with BP found. In older individuals, LVH was associated with higher central and
      brachial BP. In separate binary logistic regression analyses adjusted for
      covariates, the odds ratio for central systolic pressure was higher than those
      for brachial systolic and pulse pressure in LVH prediction. Noninvasively
      determined central pressure in subjects over 45 years is more strongly related to
      ECG LVH than brachial pressure. This further supports a closer association of
      central pressure with target organ damage. Voltage criteria of LVH are not
      independently associated with central or brachial BP in younger individuals.

PMID- 21866161
TI  - A plastidial sodium-dependent pyruvate transporter.
AB  - Pyruvate serves as a metabolic precursor for many plastid-localized biosynthetic
      pathways, such as those for fatty acids, terpenoids and branched-chain amino
      acids. In spite of the importance of pyruvate uptake into plastids (organelles
      within cells of plants and algae), the molecular mechanisms of this uptake have
      not yet been explored. This is mainly because pyruvate is a relatively small
      compound that is able to passively permeate lipid bilayers, which precludes
      accurate measurement of pyruvate transport activity in reconstituted liposomes.
      Using differential transcriptome analyses of C(3) and C(4) plants of the genera
      Flaveria and Cleome, here we have identified a novel gene that is abundant in
      C(4) species, named BASS2 (BILE ACID:SODIUM SYMPORTER FAMILY PROTEIN 2). The
      BASS2 protein is localized at the chloroplast envelope membrane, and is highly
      abundant in C(4) plants that have the sodium-dependent pyruvate transporter.
      Recombinant BASS2 shows sodium-dependent pyruvate uptake activity. Sodium influx
      is balanced by a sodium:proton antiporter (NHD1), which was mimicked in
      recombinant Escherichia coli cells expressing both BASS2 and NHD1. Arabidopsis
      thaliana bass2 mutants lack pyruvate uptake into chloroplasts, which affects
      plastid-localized isopentenyl diphosphate synthesis, as evidenced by increased
      sensitivity of such mutants to mevastatin, an inhibitor of cytosolic isopentenyl
      diphosphate biosynthesis. We thus provide molecular evidence for a sodium-coupled
      metabolite transporter in plastid envelopes. Orthologues of BASS2 can be detected
      in all the genomes of land plants that have been characterized so far, thus
      indicating the widespread importance of sodium-coupled pyruvate import into
      plastids.

PMID- 21866165
TI  - Innate immunity: AT-rich DNA trapped in the cytoplasm.

PMID- 21866167
TI  - MHC molecules: Cod's wallop? It's first class!

PMID- 21866168
TI  - Immune regulation: Worming away from TB immunity.

PMID- 21866170
TI  - Immune regulation: (micro)Control of IFNgamma.

PMID- 21866172
TI  - Homeostatic chemokine receptors and organ-specific metastasis.
AB  - It has been 10 years since the role of a chemokine receptor, CXCR4, in breast
      cancer metastasis was first documented. Since then, the field of chemokines and
      cancer has grown significantly, so it is timely to review the progress, analyse
      the studies to date and identify future challenges facing this field. Metastasis
      is the major factor that limits survival in most patients with cancer. Therefore,
      understanding the molecular mechanisms that control the metastatic behaviour of
      tumour cells is pivotal for treating cancer successfully. Substantial
      experimental and clinical evidence supports the conclusion that molecular
      mechanisms control organ-specific metastasis. One of the most important
      mechanisms operating in metastasis involves homeostatic chemokines and their
      receptors. Here, we review this field and propose a model of 'cellular highways'
      to explain the effects of homeostatic chemokines on cancer cells and how they
      influence metastasis.

PMID- 21866173
TI  - Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?
AB  - The concept that viral sensing systems, via their ability to drive pro
      inflammatory cytokine and interferon production, contribute to the development of
      autoimmune and autoinflammatory disease is supported by a wide range of clinical
      and experimental observations. Recently, the tripartite motif-containing proteins
      (TRIMs) have emerged as having key roles in antiviral immunity - either as viral
      restriction factors or as regulators of pathways downstream of viral RNA and DNA
      sensors, and the inflammasome. Given their involvement in these pathways, we
      propose that TRIM proteins contribute to the development and pathology of
      autoimmune and autoinflammatory conditions, thus making them potential novel
      targets for therapeutic manipulation.

PMID- 21866177
TI  - Advanced policy options to regulate sugar-sweetened beverages to support public
      health.
AB  - Consumption of sugar-sweetened beverages (SSBs) has increased worldwide. As
      public health studies expose the detrimental impact of SSBs, consumer protection
      and public health advocates have called for increased government control. A major
      focus has been on restricting marketing of SSBs to children, but many innovative
      policy options--legally defensible ways to regulate SSBs and support public
      health--are largely unexplored. We describe the public health, economic, and
      retail marketing research related to SSBs (including energy drinks). We review
      policy options available to governments, including mandatory factual disclosures,
      earmarked taxation, and regulating sales, including placement within retail and
      food service establishments, and schools. Our review describes recent
      international initiatives and classifies options available in the United States
      by jurisdiction (federal, state, and local) based on legal viability.

PMID- 21866176
TI  - Delivery of functional DNA and messenger RNA to mammalian phagocytic cells by
      recombinant yeast.
AB  - Among the different vaccination approaches, DNA/RNA vaccination represents a
      promising means in particular for the induction of effective cellular immune
      responses conferred by CD8-positive T lymphocytes. To achieve such immune
      responses, there is a need for novel delivery systems that allow the introduction
      of nucleic acids to the cytosol of immune cells. We show, for the first time, the
      delivery of functional DNA and messenger RNA (mRNA) to mammalian antigen
      presenting cells, including murine macrophages and human dendritic cells, using
      the yeast Saccharomyces cerevisiae as the delivery vehicle. After transfer of the
      particular nucleic acid, subsequent antigen processing and presentation were
      demonstrated in a human system. Remarkably, release of DNA/mRNA does not require
      additional 'helper' proteins such as listeriolysin. In conclusion, the yeast
      based system described here is superior to many bacterial and viral systems in
      terms of efficacy, safety and targeting suggesting 'mycofection' as a promising
      approach for the development of a novel type of live vaccines.

PMID- 21866175
TI  - The Parkinson's disease protein LRRK2 impairs proteasome substrate clearance
      without affecting proteasome catalytic activity.
AB  - Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common known cause of
      Parkinson's disease (PD). The clinical features of LRRK2 PD are indistinguishable
      from idiopathic PD, with accumulation of alpha-synuclein and/or tau and/or
      ubiquitin in intraneuronal aggregates. This suggests that LRRK2 is a key to
      understanding the aetiology of the disorder. Although loss-of-function does not
      appear to be the mechanism causing PD in LRRK2 patients, it is not clear how this
      protein mediates toxicity. In this study, we report that LRRK2 overexpression in
      cells and in vivo impairs the activity of the ubiquitin-proteasome pathway, and
      that this accounts for the accumulation of diverse substrates with LRRK2
      overexpression. We show that this is not mediated by large LRRK2 aggregates or
      sequestration of ubiquitin to the aggregates. Importantly, such abnormalities are
      not seen with overexpression of the related protein LRRK1. Our data suggest that
      LRRK2 inhibits the clearance of proteasome substrates upstream of proteasome
      catalytic activity, favouring the accumulation of proteins and aggregate
      formation. Thus, we provide a molecular link between LRRK2, the most common known
      cause of PD, and its previously described phenotype of protein accumulation.

PMID- 21866178
TI  - Mortality amenable to health care in the United States: the roles of demographics
      and health systems performance.
AB  - This article examines associations of socio-demographic and health-care
      indicators, and the statistic 'mortality amenable to health care' (amenable
      mortality) across the US states. There is over two-fold variation in amenable
      mortality, strongly associated with the percentages of state populations that are
      poor or black. Controlling for poverty and race with bi- and multi-variate
      analyses, several indicators of health system performance, such as hospital
      readmission rates and preventive care for diabetics, are significantly associated
      with amenable mortality. A significant crude association of 'uninsurance' and
      amenable mortality rates is no longer statistically significant when poverty and
      race are controlled. Overall, there appear to be opportunities for states to
      focus on specific modifiable health system performance indicators. Comparative
      rates of amenable mortality should be useful for estimating potential gains in
      population health from delivering more timely and effective care and for tracking
      the health outcomes of efforts to improve health system performance.

PMID- 21866174
TI  - Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock protein 32.
AB  - Hearing loss is often caused by death of the mechanosensory hair cells of the
      inner ear. Hair cells are susceptible to death caused by aging, noise trauma, and
      ototoxic drugs, including the aminoglycoside antibiotics and the antineoplastic
      agent cisplatin. Ototoxic drugs result in permanent hearing loss for over 500,000
      Americans annually. We showed previously that induction of heat shock proteins
      (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death in
      whole-organ cultures of utricles from adult mice. In order to begin to translate
      these findings into a clinical therapy aimed at inhibiting ototoxic drug-induced
      hearing loss, we have now examined a pharmacological HSP inducer, celastrol.
      Celastrol induced upregulation of HSPs in utricles, and it provided significant
      protection against aminoglycoside-induced hair cell death in vitro and in vivo.
      Moreover, celastrol inhibited hearing loss in mice receiving systemic
      aminoglycoside treatment. Our data indicate that the major heat shock
      transcription factor HSF-1 is not required for celastrol-mediated protection.
      HSP32 (also called heme oxygenase-1, HO-1) is the primary mediator of the
      protective effect of celastrol. HSP32/HO-1 inhibits pro-apoptotic c-Jun N
      terminal kinase (JNK) activation and hair cell death. Taken together, our data
      indicate that celastrol inhibits aminoglycoside ototoxicity via HSP32/HO-1
      induction.

PMID- 21866179
TI  - Legal aspects of public health: how law frames communicable disease control in
      Greece.
AB  - We reviewed Greek law (legislation, historic Royal Decrees, and modern
      Presidential ones, 1833-2010) pertinent to control of communicable diseases and
      compared this body of Greek law with the revised International Health
      Regulations. Greece authorizes and regulates communicable disease control
      commensurate with public health risks, and integrates the principles of equality,
      objectivity, and respect for human rights. Despite strength at the level of
      principles, Greek law lacks coherence, clarity, and systematization. An
      inadequate body of regulations means legislation falls short of adequate
      implementing authority and guidelines; public health authorities often cannot
      find or understand the laws, nor are they certain about allocation of
      jurisdictional authority. We identified areas for improvement.

PMID- 21866180
TI  - Care drain: the political making of health worker migration.
AB  - Migration of formal and informal health-care workers is a global phenomenon -
      and, as this article demonstrates, one that is produced by government policies
      and practices. Nurses and lesser-trained caregivers migrate from many lower
      income countries to richer ones (including from the Philippines to the United
      States, from South Africa to England, from Central Asia to Turkey). Using the
      Austrian experience to illustrate how policies and lack of enforcement of labor
      laws lead to migration and mistreatment of health-care professionals and informal
      caregivers, this article recommends how to alleviate health-care staff shortages
      in Africa and elsewhere through policymaking in Europe and North America.
      Recognition of the political dimensions of health-care migration is the first
      step toward addressing ethical questions and damaging shortages of caregivers.

PMID- 21866181
TI  - A biogeographic distribution of magnetotactic bacteria influenced by salinity.
AB  - Magnetotactic bacteria (MTB), which synthesize intracellular ferromagnetic
      magnetite and/or greigite magnetosomes, have significant roles in global iron
      cycling in aquatic systems, as well as sedimentary magnetism. The occurrence of
      MTB has been reported in aquatic environments from freshwater to marine
      ecosystems; however, the distribution of MTB across heterogeneous habitats
      remains unclear. Here we examined the MTB communities from diverse habitats
      across northern and southern China, using comprehensive transmission electron
      microscopy and comparison of 16S rRNA gene analyses. A total of 334 16S rRNA gene
      sequences were analyzed, representing the most comprehensive analysis on the
      diversity and distribution of MTB to date. The majority (95%) of sequences belong
      to the Alphaproteobacteria, whereas a population of giant magnetotactic rod is
      affiliated with the Nitrospirae phylum. By a statistical comparison of these
      sequence data and publicly available MTB sequences, we infer for the first time
      that the composition of MTB communities represents a biogeographic distribution
      across globally heterogeneous environments, which is influenced by salinity.

PMID- 21866182
TI  - The genome of the obligate endobacterium of an AM fungus reveals an interphylum
      network of nutritional interactions.
AB  - As obligate symbionts of most land plants, arbuscular mycorrhizal fungi (AMF)
      have a crucial role in ecosystems, but to date, in the absence of genomic data,
      their adaptive biology remains elusive. In addition, endobacteria are found in
      their cytoplasm, the role of which is unknown. In order to investigate the
      function of the Gram-negative Candidatus Glomeribacter gigasporarum, an
      endobacterium of the AMF Gigaspora margarita, we sequenced its genome, leading to
      an ~1.72-Mb assembly. Phylogenetic analyses placed Ca. G. gigasporarum in the
      Burkholderiaceae whereas metabolic network analyses clustered it with insect
      endobacteria. This positioning of Ca. G. gigasporarum among different bacterial
      classes reveals that it has undergone convergent evolution to adapt itself to
      intracellular lifestyle. The genome annotation of this mycorrhizal-fungal
      endobacterium has revealed an unexpected genetic mosaic where typical
      determinants of symbiotic, pathogenic and free-living bacteria are integrated in
      a reduced genome. Ca. G. gigasporarum is an aerobic microbe that depends on its
      host for carbon, phosphorus and nitrogen supply; it also expresses type II and
      type III secretion systems and synthesizes vitamin B12, antibiotics- and toxin
      resistance molecules, which may contribute to the fungal host's ecological
      fitness. Ca. G. gigasporarum has an extreme dependence on its host for nutrients
      and energy, whereas the fungal host is itself an obligate biotroph that relies on
      a photosynthetic plant. Our work represents the first step towards unraveling a
      complex network of interphylum interactions, which is expected to have a
      previously unrecognized ecological impact.

PMID- 21866183
TI  - Ethnic differences in the effects of the DASH diet on nocturnal blood pressure
      dipping in individuals with high blood pressure.
AB  - BACKGROUND: Ethnic differences in nocturnal blood pressure (BP) dipping may
      contribute to the increased risk for adverse cardiovascular events noted in
      African Americans (AAs). The DASH (Dietary Approaches to Stop Hypertension) diet
      has been shown to be efficacious in lowering clinic and ambulatory BP; however,
      the effect of the DASH diet on BP dipping is unclear. METHODS: One hundred and
      eighteen men and women with high clinic BP (systolic BP (SBP) 130-159; diastolic
      BP 85-99) and above ideal body weight were randomized to a DASH diet intervention
      or to a usual diet control (UC) condition. Measures of 24-h ambulatory BP were
      obtained at baseline and at the end of the 4-month intervention period. RESULTS:
      At baseline, AAs (n = 43) displayed blunted nocturnal SBP dipping compared to
      Caucasians (CAs; n = 75) and were more likely to be categorized as nondippers
      (<10% nocturnal decline in SBP, AAs: 51% vs. CAs: 27%). AAs randomized to the
      DASH diet intervention showed a significant improvement in SBP dipping
      postintervention compared to AAs in the UC condition (P = 0.04), whereas there
      was no appreciable change in SBP dipping in CAs (P = 0.72). Following the
      intervention, ethnic differences in SBP dipping were no longer statistically
      significant (nondipper status: AAs: 44% vs. CAs: 32%; P = 0.19). CONCLUSIONS: Our
      study provides preliminary evidence suggesting that in overweight men and women
      with high BP, AAs may be especially likely to benefit from augmented SBP dipping
      associated with consumption of the DASH diet.

PMID- 21866184
TI  - Nondipping pattern and carotid atherosclerosis in a middle-aged population: OPERA
      Study.
AB  - BACKGROUND The lack of dropping in night-time blood pressure of 10% or more
      (nondipping) seems to associate with cardiovascular risk factors. The
      relationship between the dipping pattern and atherosclerosis is not clear. The
      night-time systolic blood pressure (SBP) determines the dipping status. METHODS:
      We investigated the connection between intima-media thickness (IMT) and dipping
      status (dipper, nondipper) taking into account covariates known to associate with
      hypertension and early atherosclerosis. 900 middle-aged (446 men, 454 women) were
      studied, 51% of them using blood pressure lowering medication. IMT was measured
      by a duplex ultrasound from the common carotid artery (CCA), the internal carotid
      artery (ICA) and the bifurcation enlargement (BIF). The mean IMT was defined as
      the mean of ICA, BIF, and the 3 highest CCA measurements. Ambulatory blood
      pressure (ABP) was recorded using the fully automatic SpaceLabs90207
      oscillometric unit. RESULTS: Nondippers had lower high-density lipoprotein
      cholesterol (P = 0.02), higher triglycerides (P < 0.01), body mass index (P <
      0.0001) and higher night-time blood pressure (P < 0.0001) than dippers and they
      were more often nonsmokers (P = 0.01). Increased mean IMT in carotid artery was
      associated with ABP nondipping pattern (P < 0.01) regardless of conventional
      cardiovascular risk factors, antihypertensive or lipid lowering medications.
      Nocturnal blood pressure elevation was independently associated with IMT (P <
      0.01). When sexes were analysed separately, the association was seen in men but
      was only a trend among women. CONCLUSIONS: Nondipping status in ABP monitoring is
      independently associated with early atherosclerosis. Whether nondipping pattern
      is a predictor of atherosclerosis remains to be explored in a future prospective
      follow-up of this cohort.

PMID- 21866185
TI  - Predictors of blood pressure control among hypertensives in community health
      centers.
AB  - BACKGROUND: The correlates of blood pressure (BP) control among hypertensive
      individuals who have access to care in community-based health-care settings are
      poorly characterized, particularly among minority and immigrant populations.
      METHODS: Using data extracted from electronic medical records in four federally
      qualified health centers in New York, we investigated correlates of hypertension
      (HTN) control in cross-sectional analyses. The sample consisted of adult,
      nonobstetric patients with a diagnosis of HTN and a clinic visit between June
      2007 and October 2008 (n = 2,585). RESULTS: Forty-nine percent of hypertensive
      patients had controlled BP at their last visit. Blacks had a higher prevalence of
      HTN (B, 32.8%; W, 16.2%; H, 11.5%) and were less likely to have controlled BP (B,
      42.2%; W, 50.9%; H, 50.8%) compared with Hispanics and whites. Medication
      intensification did not differ by race/ethnicity. In multivariate analyses higher
      body mass index (BMI), black race, diabetes, fewer clinical encounters, and male
      gender were associated with poor BP control. However, when we applied the Seventh
      Report of the Joint National Committee (JNC 7) definition for BP control for
      nondiabetic patients (systolic blood pressure (SBP) <140, diastolic blood
      pressure (DBP) <90) to all patients with HTN, we found no difference in BP
      control between those with and without diabetes. CONCLUSIONS: Blacks had poorer
      HTN control compared with whites and Hispanics. Significant discrepancies in BP
      control between hypertensive patients with and without diabetes may be related to
      a lack of provider adherence to JNC 7 guidelines that define BP control in this
      population as <130/80. Further research is needed to understand racial
      disparities in BP control as well as factors influencing clinician's management
      of BP among patients with diabetes.

PMID- 21866186
TI  - Validating a new oscillometric device for aortic pulse wave velocity measurements
      in children and adolescents.
AB  - BACKGROUND: Pulse wave velocity (PWV) is an indicator of aortic stiffness and a
      predictor of cardiovascular risk. Applanation tonometry (e.g., SphygmoCor) is a
      well-established method to measure aortic PWV (aPWV). The Vicorder, a new
      oscillometric device, has not been validated in children and adolescents.
      METHODS: We performed intra- and interobserver repeatability studies in 14
      individuals using the Vicorder. Vicorder and SphygmoCor measurements were
      compared in 156 healthy children (6-18 years) using two different path length
      measurements. RESULTS: Intra- and interobserver repeatabilities of the Vicorder
      were excellent with coefficients of variation of 5.6% and 5.8% and intraclass
      correlation coefficients (ICCs) of 0.8 and 1.0. aPWV calculated using the
      distances (suprasternal notch-to-femoral recording point) - (suprasternal notch
      to-carotid artery), the path length most commonly used in adults, revealed a mean
      of 4.8 +/- 0.7 m/s for SphygmoCor and 4.9 +/- 0.6 m/s for Vicorder. The
      percentage deviation between both devices was 13.0% and the limit of agreement
      (LoA) ranged from -1.0 to 1.7 m/s reflecting a good concordance. Using a path
      length that measured the distance from suprasternal notch to femoral recording
      point via the umbilicus (Umb), an even better agreement was found (percentage
      deviation: 11.8%, LoA: -1.0 to 1.6 m/s). CONCLUSIONS: Vicorder aPWV values are
      similar to those obtained by SphygmoCor applanation tonometry. The best agreement
      between devices was obtained with the path length that most accurately describes
      the aortic tree. Excellent intra- and interobserver repeatability and ease of
      measurements make Vicorder appropriate for large multicentre studies in children
      and adolescents.

PMID- 21866189
TI  - [Clinical registries can be used better].

PMID- 21866188
TI  - Phenylethanolamine N-methyltransferase gene promoter haplotypes and risk of
      essential hypertension.
AB  - BACKGROUND: Phenylethanolamine N-methyltransferase gene (PNMT) catalyzes the
      synthesis of epinephrine and plays an important role in regulating cardiovascular
      function. Genetic variation in the PNMT promoter is reportedly associated with
      the risk of essential hypertension in certain population. METHODS: In the present
      study, we explored the association of two common PNMT promoter single-nucleotide
      polymorphisms (SNPs) G-367A (rs3764351) and G-161A (rs876493) and their
      haplotypes with the risk of essential hypertension in a Han Chinese population,
      using 316 pairs of age-, sex-, and geographically matched essential hypertension
      patients and normotensive controls. RESULTS: No significant difference in allele
      and genotype frequencies at either G-367A (rs3764351) or G-161A (rs876493) was
      observed between essential hypertension patients and normotensive controls.
      However, the 2-SNP AA haplotype was found significantly more common in
      normotensive controls than in essential hypertensive patients (P = 0.01; adjusted
      odds ratios, 0.17; 95% confidence interval, 0.05-0.58). CONCLUSIONS: The 2-SNP AA
      haplotype in the PNMT promoter is associated with decreased risk of essential
      hypertension in Han Chinese. This is the first evidence of an association between
      a PNMT promoter haplotype and the risk of essential hypertension.

PMID- 21866187
TI  - Interdependency of cystathione gamma-lyase and cystathione beta-synthase in
      hydrogen sulfide-induced blood pressure regulation in rats.
AB  - BACKGROUND: Hydrogen sulfide (H(2)S), an endogenous vasoactive agent, is produced
      by cystathionine gamma-lyase (CGL) and cystathionine beta-synthase (CBS) enzymes.
      This study was conducted to evaluate the relative contribution of these enzymes
      in regulating systemic arterial pressure. METHODS: Sprague-Dawley rats were
      chronically treated with CGL inhibitor, DL-propargylglycine (PAG, 37.5 mg/kg/day;
      intraperitoneally, i.p.) or CBS inhibitor, aminooxyacetic acid (AOA, 8.75
      mg/kg/day; i.p.) or in combination for 4 weeks and the effects on arterial
      pressure (tail-cuff plethysmography) and renal excretory function (24 h urine
      collections using metabolic cages) were assessed once in a week. Changes in renal
      blood flow (RBF; Ultrasonic flowmetry) and glomerular filtration rate (GFR;
      Inulin clearance) were assessed in acute experiments in anesthetized rats at the
      end of treatment period. RESULTS: Compared to vehicle treated control group, only
      the rats with combination therapy showed a decrease in urinary sulfate excretion
      rate (248 +/- 47 vs. 591 +/- 70 nmol/24 h; marker for endogenous H(2)S level)
      which was associated with an increase in mean arterial pressure (MAP; 130 +/- 2
      vs. 99 +/- 2 mm Hg). Urine flow and sodium excretion were also increased in
      combination group as consequent to the increase in MAP. GFR did not alter due to
      these treatments but RBF was lowered (4 +/- 0.3 vs. 7 +/- 0.4 ml/min/g) only in
      the combination group compared to the control group. CONCLUSION: These findings
      indicate that a deficiency in one enzyme's activity could be compensated by the
      activity of the other to maintain the endogenous H(2)S level, the deficiency of
      which modulates systemic and renal vascular resistances leading to the
      development of hypertension.

PMID- 21866191
TI  - [Still wrong about Kant].

PMID- 21866190
TI  - [Knowledge about knowledge].

PMID- 21866192
TI  - [Children don't have time to wait].

PMID- 21866193
TI  - Hip arthroplasty in Norway 1989-2008.
AB  - BACKGROUND: Since information on regional variation in the frequency of primary
      total hip arthroplasty in Norway is scarce, we studied differences by county and
      regional health authority throughout the last 20 years. MATERIAL AND METHODS: We
      included 112, 514 primary total hip arthroplasties reported to the Norwegian
      Arthroplasty Register in the years 1989-2008. Annual gender and age standardized
      frequencies were calculated, and Poisson regression was used for group
      comparisons (RR = rate ratio). RESULTS: We observed an increase in hip
      arthroplasty frequency from 109 operations per 100, 000 inhabitants in the years
      1991-1995 to 140 in 2006-2008 (RR = 1.28), and more so for operations performed
      due to coxarthrosis (RR = 1.46). An increased frequency over time was evident in
      all five regions and 19 counties. Differences between counties and regions had
      decreased throughout the study period. In the years 2006-2008, Helse Midt (152
      operations) had a statistically significant higher frequency than the other
      regions except for Helse Sor. The lowest frequencies at county level were found
      for Finnmark (116 operations) and the highest for Aust-Agder (172).
      INTERPRETATION: While regional differences have decreased since the early 1990 s,
      existing differences may in part be due to differing access to surgery, varying
      indications for surgery, or possibly also genetic or cultural differences.

PMID- 21866194
TI  - [Peritoneal dialysis at a regional hospital in Norway].
AB  - BACKGROUND: In 2006, an expert group appointed by the Norwegian Social and Health
      Directory recommended that the proportion of patients on peritoneal dialysis
      should increase from 15 % to about 30 %. We wanted to investigate if treatment in
      our hospital was in compliance with that recommendation. MATERIAL AND METHODS:
      The patient material consisted of the total number of patients on dialysis and
      anonymised data collected for patients treated with peritoneal dialysis at
      Innlandet Hospital Trust, Lillehammer in the period 1.01.2004-31.12.2008. For
      patients in peritoneal dialysis we assessed patient dynamics, length of hospital
      stay, incidence of peritonitis, need for assistance and organisation of
      peritoneal dialysis activity. RESULTS: Dialysis treatment was given to 176
      patients, 62 (35 %) of whom were treated by peritoneal dialysis for at least 30
      days (mean treatment time 16.2 months). 17 patients were switched from
      hemodialysis to peritoneal dialysis and nine patients from peritoneal dialysis to
      hemodialysis. Patients older than 70 years stayed in hospital 6 days longer than
      those younger than 70 years. 27 (44 %) of the patients acquired peritonitis in
      the study period and 18 (29 %) patients needed help to exchange the dialysis bag.
      INTERPRETATION: The proportion of patients treated with peritoneal dialysis in
      our hospital has reached the recommended level. The reason may be that all
      eligible patients are offered peritoneal dialysis and that the treatment chain is
      well organised.

PMID- 21866195
TI  - [Mass examination for gynecological cancer--status and future].
AB  - BACKGROUND: In Norway, mass examination for cervical cancer was started in 1995
      with the goal to reduce incidence and mortality through rational use of
      resources. This has been successful. We wished to assess the knowledge base for
      this practice, as well as that on usefulness of mass examination for ovarian
      cancer and uterine body cancer. MATERIAL AND METHOD: This article is based on
      literature identified through a non-systematic search in PubMed. RESULTS: Despite
      knowledge of several risk factors for uterine body cancer, there is not
      sufficient evidence to support mass examination for this condition. Within a few
      years it will become clear whether large ongoing studies provide sufficient
      evidence to recommend screening for ovarian cancer. The effect of mass
      examination for cervical cancer is well documented. INTERPRETATION: Cervical
      cancer is the only gynecological condition with an established mass examination
      program. This program must be adapted to new methods and the population's vaccine
      status in the coming years. There is not sufficient documentation on ovarian
      cancer or uterine body cancer to support mass examination, but this may change
      during a few years.

PMID- 21866196
TI  - Prevention of Legionnaires' disease in hospitals.
AB  - BACKGROUND: The first instance of Legionella infection in a Norwegian hospital
      was confirmed in 2005. We describe the best-known methods of eradicating
      Legionella in hospitals. MATERIALS AND METHOD: The article is based on the
      authors' experience of measures to prevent Legionnaires' disease in hospitals and
      on a non-systematic search in PubMed. RESULTS: There are several methods of
      combating Legionella in hospitals. These include chlorination, heat treatment,
      and the use of filters. However, recontamination easily re-occurs after
      eradication. The silver and copper ionisation treatment of water is a well
      documented method for the systematic and long-term eradication of Legionella in
      water. The disadvantages of this method are that it is expensive, that there is a
      risk of discolouring the water, and that there is a possibility of developing
      resistance in environmental bacteria. This resistance mechanism can theoretically
      be transferred to bacteria that cause illness. INTERPRETATION: We recommend the
      silver and copper ionisation treatment of water as a method of preventing
      nosocomial Legionnaires' disease when standard methods fail and there is a high
      prevalence of Legionella in the water. The discolouration of operation
      instruments that occurs as a result of high silver concentrations can be avoided
      by using a separate water supply for operation units.

PMID- 21866198
TI  - [What can health personnel do with social health inequalities?].

PMID- 21866197
TI  - Cerebral arterial vasospasm.

PMID- 21866199
TI  - [Internship and specialist education--a nervous romance].

PMID- 21866200
TI  - Collaboration in psychiatry between Archangelsk and Northern Norway.

PMID- 21866203
TI  - Unique Cytokine/Chemokine Signatures for HIV-1 and HCV Mono-infection versus Co
      infection as Determined by the Luminex(r) Analyses.
AB  - Liver disease caused by HIV-1/HCV co-infection is characterized by the
      inflammation and cell-death. The co-existence of these two chronic viral
      infections also alters the cytokine production in vivo. The ability to visualize
      changes in cytokine networks with the onset and progression of disease or
      treatment is critical to advance our understanding of the immune response to
      pathogens. The recent Luminex(r) technology has revolutionized the simultaneous
      detection and quantitation of several cytokines and chemokines in clinical
      samples that are generally available in small quantities. We have applied this
      technology to analyze the plasma samples from patients who have either HIV-1 or
      HCV mono-infection or HIV-1/HCV co-infection and monitored the presence of 23
      cytokines and chemokines. Of these, 8 (IFN-alpha2, IL-2, IL-3, IL-6, IL-8, IL
      12p70, IL-15 and RANTES) cytokines were expressed at higher levels in the co
      infected individuals. Interestingly, in case of HIV-1 mono-infected individuals,
      the levels of the proinflammatory cytokines IFN-gamma and TNF-alpha were
      increased. Standard correlation clustering of the normalized data demonstrated
      unique plasma cytokine signatures for HIV-1/HCV co-infected individuals. These
      signatures were characterized not only by an up regulation of the aforementioned
      antiviral mediators but also by a marked down regulation in the chemokines
      Eotaxin and MIP-1alpha when compared to mono-infected individuals. Luminex(r)-
      based analyses have proven to be a powerful tool for therapeutic
      immunomonitoring, but may have an even greater impact in the discovery of the
      underlying immune response at all phases of infection. The study presented herein
      has potential to offer insight into the underlying mechanisms of
      immunopathogenesis of HIV-1/HCV co-infection.

PMID- 21866204
TI  - Diastereo- and Enantioselective Reductive Aldol Addition of Vinyl Ketones via
      Catalytic Hydrogenation.
AB  - An overview of studies on hydrogenative reductive aldol addition is presented. By
      simply hydrogenating enones in the presence of aldehydes at ambient temperature
      and pressure, aldol adducts are generated under neutral conditions in the absence
      of any stoichiometric byproducts. Using cationic rhodium complexes modified by
      tri(2-furyl)phosphine, highly syn-diastereoselective reductive aldol additions of
      vinyl ketones are achieved. Finally, using novel monodentate TADDOL-like
      phosphonite ligands, the first highly diastereo- and enantioselective reductive
      aldol couplings of vinyl ketones were devised. These studies, along with other
      works from our laboratory, demonstrate that organometallics arising transiently
      in the course of catalytic hydrogenation offer byproduct-free alternatives to
      preformed organometallic reagents employed in classical carbonyl addition
      processes.

PMID- 21866205
TI  - Retinal Nerve Fibre Layer and Macular Thinning in Spinocerebellar Ataxia and
      Cerebellar Multisystem Atrophy.
AB  - The spinocerebellar ataxias, like all neurodegenerative diseases, lack objective
      disease- and stage-specific biomarkers. Based on reports of clinically evident
      optic disc atrophy or retinal disease in some ataxia patients, and the discovery
      that pre-symptomatic retinal thinning occurs in other neurologic diseases such as
      multiple sclerosis, we tested the hypothesis that subclinical neuronal or axonal
      loss in the retina could occur in the degenerative ataxias. Spectral domain
      optical coherence tomography was performed on 29 ataxia patients with genetically
      proven spinocerebellar ataxia (SCA) 1, 2, 3, or 6, or multisystem atrophy type C
      (MSA-C) and 27 age-matched normal subjects. Ataxia patients were assessed using
      the scale for assessment and rating of ataxia. Compared with normal control
      subjects, retinal nerve fibre layer (RNFL) thickness was reduced for patients
      with SCA2 and SCA3, and thickness in the macular region was reduced for all SCAs
      but SCA2.

PMID- 21866206
TI  - Children's Responses to Group-Based Inequalities: Perpetuation and Rectification.
AB  - The current studies investigate whether, and under what conditions, children
      engage in system-perpetuating and system-attenuating behaviors when allocating
      resources to different social groups. In three studies, we presented young
      children with evidence of social group inequalities and assessed whether they
      chose to perpetuate or rectify these inequalities. Children (aged 3.5-11.5 years)
      heard about two social groups (i.e., racial or novel groups) whose members
      received resources unequally(two cookies versus one). Participants were then
      given the opportunity to distribute additional resources to new members of the
      same groups. In Experiment 1, when children were presented with inequalities
      involving groups of Blacks and Whites, older children (aged 7.5-11.5 years)
      rejected the status quo, providing more resources to members of groups with fewer
      resources (White or Black), whereas younger children (aged 3.5-7.5 years)
      perpetuated the status quo. In Experiments 2 and 3, the inequalities involved
      Asians and Whites and novel groups. Children of all ages perpetuated inequality,
      with rectification strategies applied only by older children and only when Black
      targets were involved in the inequality. Equal sharing occasionally occurred in
      older children but was never a common response. These findings provide evidence
      that system-perpetuating tendencies may be predominant in children and suggest
      that socialization may be necessary to counter them.

PMID- 21866207
TI  - Adult Mortality and Natural Resource Use in Rural South Africa: Evidence From the
      Agincourt Health and Demographic Surveillance Site.
AB  - There is little empirical evidence on the association between household
      experience with HIV/AIDS and shifts in the use of natural resources in developing
      countries, where residents of rural regions remain highly dependent on often
      declining local supplies of natural resources. This study examines household
      strategies with regard to fuelwood and water among impoverished rural South
      African households having experienced a recent adult mortality and those without
      such mortality experience. Quantitative survey data reveal higher levels of
      natural resource dependence among mortality-affected households, as well as
      differences in collection strategies. Qualitative interview data provide insight
      into subtle and complex adjustments at the household level, revealing that
      impacts vary by the role of the deceased within the household economy. Resource
      management and public health implications are explored.

PMID- 21866208
TI  - Heterogeneous Anthropomorphic Phantoms with Realistic Dielectric Properties for
      Microwave Breast Imaging Experiments.
AB  - We present a technique for fabricating realistic breast phantoms for microwave
      imaging experiments. Using oil-in-gelatin dispersions that mimic breast tissue
      dielectric properties at microwave frequencies, we constructed four heterogeneous
      phantoms spanning the full range of volumetric breast densities. We performed CT
      scans and dielectric properties measurements to characterize each phantom.

PMID- 21866209
TI  - Singular Parameter Prediction Algorithm for Bistable Neural Systems.
AB  - An algorithm is presented to predict the intensity and timing of a singular
      single stimulus required to switch the state of a bistable system from repetitive
      activity to a stable point. The algorithm is first tested on a modified Hodgkin
      Huxley model to predict the parameters of a stimulus capable of annihilating the
      spontaneously occurring repetitive action potentials. Elevation of the potassium
      equilibrium potential causes oscillations in the V, m, h and n parameters and
      generates periodic activity. Equations describing the time-varying behavior of
      these parameters can be used to predict the pulse width, coupling interval and
      intensity of a single anodic pulse applied between two consecutive action
      potentials to suppress the activity. The algorithm was then applied to predict
      the singular parameters of quasi-periodic epileptiform activity generated in the
      hippocampus slice preparation exposed to high-potassium concentrations. The
      results indicate that a stimulus with the estimated parameters was able to either
      completely annihilate the action potentials in the HH model or predict the region
      of unpredictable latencies. Therefore this algorithm is capable a predicting
      singular parameters accurately when the model is known. In the case of an
      experimental system where the equations of the system are not known, the
      algorithm predicted parameters in the range of those observed experimentally.
      Therefore, the algorithm could reduce significantly the amount of time required
      to find the singular parameters of experimental bistable systems normally
      obtained by a systematic exploration of the parameter space. In particular, this
      algorithm could be useful to predict the singular parameters of quasi periodic
      epileptiform activity leading to the suppression of this activity if the system
      is bistable.

PMID- 21866210
TI  - Interactive segmentation for geographic atrophy in retinal fundus images.
AB  - Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo
      ophthalmoscopic inspection of age-related macular degeneration (AMD), the most
      common cause of blindness in developed countries. Geographic atrophy (GA) is an
      advanced form of AMD and accounts for 12-21% of severe visual loss in this
      disorder [3]. Automatic quantification of GA is important for determining disease
      progression and facilitating clinical diagnosis of AMD. The problem of automatic
      segmentation of pathological images still remains an unsolved problem. In this
      paper we leverage the watershed transform and generalized non-linear gradient
      operators for interactive segmentation and present an intuitive and simple
      approach for geographic atrophy segmentation. We compare our approach with the
      state of the art random walker [5] algorithm for interactive segmentation using
      ROC statistics. Quantitative evaluation experiments on 100 FAF images show a mean
      sensitivity/specificity of 98.3/97.7% for our approach and a mean
      sensitivity/specificity of 88.2/96.6% for the random walker algorithm.

PMID- 21866211
TI  - Alterations of epithelial stem cell marker patterns in human diabetic corneas and
      effects of c-met gene therapy.
AB  - PURPOSE: We have previously identified specific epithelial proteins with altered
      expression in human diabetic central corneas. Decreased hepatocyte growth factor
      receptor (c-met) and increased proteinases were functionally implicated in the
      changes of these proteins in diabetes. The present study examined whether limbal
      stem cell marker patterns were altered in diabetic corneas and whether c-met gene
      overexpression could normalize these patterns. METHODS: Cryostat sections of 28
      ex vivo and 26 organ-cultured autopsy human normal and diabetic corneas were
      examined by immunohistochemistry using antibodies to putative limbal stem cell
      markers including ATP-binding cassette sub-family G member 2 (ABCG2), N-cadherin,
      DeltaNp63alpha, tenascin-C, laminin gamma3 chain, keratins (K) K15, K17, K19,
      beta(1) integrin, vimentin, frizzled 7, and fibronectin. Organ-cultured diabetic
      corneas were studied upon transduction with adenovirus harboring c-met gene.
      RESULTS: Immunostaining for ABCG2, N-cadherin, DeltaNp63alpha, K15, K17, K19, and
      beta(1) integrin, was significantly decreased in the stem cell-harboring diabetic
      limbal basal epithelium either by intensity or the number of positive cells.
      Basement membrane components, laminin gamma3 chain, and fibronectin (but not
      tenascin-C) also showed a significant reduction in the ex vivo diabetic limbus. c
      Met gene transduction, which normalizes diabetic marker expression and epithelial
      wound healing, was accompanied by increased limbal epithelial staining for K17,
      K19, DeltaNp63alpha, and a diabetic marker alpha(3)beta(1) integrin, compared to
      vector-transduced corneas. CONCLUSIONS: The data suggest that limbal stem cell
      compartment is altered in long-term diabetes. Gene therapy, such as with c-met
      overexpression, could be able to restore normal function to diabetic corneal
      epithelial stem cells.

PMID- 21866212
TI  - Pharmacokinetics of pirfenidone after topical administration in rabbit eye.
AB  - PURPOSE: Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum
      agent that has an inhibition effect on the proliferation, migration, and collagen
      contraction of human Tenon's fibroblasts, and thus modulating the wound healing
      process of glaucoma filtering surgical site. This study investigated the
      pharmacokinetics of topically administered pirfenidone (0.5%) in rabbit eyes.
      METHODS: Pirfenidone solution (50 MUl) was instilled into the rabbit's
      conjunctival sac. The rabbits were quickly sacrificed at 2, 5, 8, 10, 15, 20, 30,
      60, 90, and 120 min after the administration and ocular tissues were obtained.
      The concentrations of pirfenidone in conjunctiva, sclera, cornea, aqueous humor,
      and vitreous were determined by high performance liquid chromatography. RESULTS:
      After topical administration, there was wide distribution and fast clearance of
      pirfenidone among the various ocular tissues. The mean maximum concentrations
      (C(max)) of pirfenidone in cornea, conjunctiva, sclera, aqueous humor, and
      vitreous were 9.64 mg/g, 9.62 mg/g, 2.13 mg/g, 34.88 mg/l and 0.52 mg/l,
      respectively. The half-life for these tissues was 18.26, 34.16, 15.71, 70.91, and
      39.48 min, respectively. CONCLUSIONS: Measurable concentrations of pirfenidone
      are achieved in ocular tissues after topical application in rabbit model. Topical
      administration of pirfenidone may be an effective approach for modulation of
      wound healing responses in glaucoma filtration surgical site.

PMID- 21866214
TI  - Novel human CRYGD rare variant in a Brazilian family with congenital cataract.
AB  - PURPOSE: To describe a novel polymorphism in the gammaD-crystallin (CRYGD) gene
      in a Brazilian family with congenital cataract. METHODS: A Brazilian four
      generation family was analyzed. The proband had bilateral lamellar cataract and
      the phenotypes were classified by slit lamp examination. Genomic DNA was
      extracted from peripheral blood and coding regions and intron/exon boundaries of
      the alphaA-crystallin (CRYAA), gammaC-crystallin (CRYGC), and CRYGD genes were
      amplified by polymerase chain reaction and directly sequenced. RESULTS:
      Sequencing of the coding regions of CRYGD showed the presence of a heterozygous A
      >G transversion at c.401 position, which results in the substitution of a
      tyrosine to a cysteine (Y134C). The polymorphism was identified in three
      individuals, two affected and one unaffected. CONCLUSIONS: A novel rare variant
      in CRYGD (Y134C) was detected in a Brazilian family with congenital cataract.
      Because there is no segregation between the substitution and the phenotypes in
      this family, other genetic alterations are likely to be present.

PMID- 21866216
TI  - ?
AB  - Le genre endemique malgache Bathiorhamnus Capuron (Rhamnaceae) est l'objet d'une
      revision taxonomique. L'etude des caracteres morphologiques permet de reconnaitre
      sept especes. En plus des deux especes anterieurement reconnues: B. cryptophorus
      Capuron et B. louvelii (H.Perrier) Capuron, les trois varietes reconnues dans la
      seconde sont reevaluees et elevees au rang d'espece: B. dentatus (Capuron)
      Callm., Phillipson & Buerki, B. macrocarpus (Capuron) Callm., Phillipson &
      Buerki, B. reticulatus (Capuron) Callm., Phillipson & Buerki. Deux nouvelles
      especes sont decrites: B. capuronii Callm., Phillipson & Buerki, des forets
      seches de l'ouest et du nord et B. vohemarensis Callm., Phillipson & Buerki des
      forets littorales situees autour de Vohemar au nord-est. Une cle du genre
      Bathiorhamnus est presentee ainsi qu'une evaluation preliminaire du statut de
      conservation de chaque espece.

PMID- 21866215
TI  - Auditory sensitivity and the outer hair cell system in the CBA mouse model of age
      related hearing loss.
AB  - Age-related hearing loss is a highly prevalent sensory disorder, from both the
      clinical and animal model perspectives. Understanding of the neurophysiologic,
      structural, and molecular biologic bases of age-related hearing loss will
      facilitate development of biomedical therapeutic interventions to prevent, slow,
      or reverse its progression. Thus, increased understanding of relationships
      between aging of the cochlear (auditory portion of the inner ear) hair cell
      system and decline in overall hearing ability is necessary. The goal of the
      present investigation was to test the hypothesis that there would be correlations
      between physiologic measures of outer hair cell function (otoacoustic emission
      levels) and hearing sensitivity (auditory brainstem response thresholds),
      starting in middle age. For the CBA mouse, a useful animal model of age-related
      hearing loss, it was found that correlations between these two hearing measures
      occurred only for high sound frequencies in middle age. However, in old age, a
      correlation was observed across the entire mouse range of hearing. These findings
      have implications for improved early detection of progression of age-related
      hearing loss in middle-aged mammals, including mice and humans, and
      distinguishing peripheral etiologies from central auditory system decline.

PMID- 21866213
TI  - Mutation analysis of 12 genes in Chinese families with congenital cataracts.
AB  - PURPOSE: To identify mutations in 12 genes in Chinese families with congenital
      cataracts. METHODS: Twenty five families with congenital cataracts involved in
      this study. The coding exons and adjacent intronic regions of 12 genes were
      analyzed by cycle sequencing, including the alpha A crystallin (CRYAA), alpha B
      crystallin (CRYAB), beta A1 crystallin (CRYBA1), beta A4 crystallin (CRYBA4),
      beta B1 crystallin (CRYBB1), beta B2 crystallin (CRYBB2), beta B3 crystallin
      (CRYBB3), gamma C crystallin (CRYGC), gamma D crystallin (CRYGD), gamma S
      crystallin (CRYGS), alpha 3 gap junction protein (GJA3), and alpha 8 gap junction
      protein (GJA8) genes. Novel variants were further evaluated in 96 normal
      controls. RESULTS: Nine mutations were identified in 10 of the 25 families (40%),
      including 5 novel (c.350_352delGCT in CRYAA, c.205C>T in CRYAB, c.106G>C in
      CRYGD, c.77A>G in CRYGS, c.1143_1165del23 in GJA3) and 4 known (c.292G>A in
      CRYAA; c.215+1G>A and c.272_274delGAG in CRYBA1, and c.176C>T in GJA3). All novel
      mutations were predicted to be pathogenic and were not present in 96 controls.
      CONCLUSIONS: Mutations in the 12 genes encoding crystallins and connexins were
      responsible for 40% Chinese families with congenital cataracts. Our results
      enriched our knowledge on the molecular basis of congenital cataracts in Chinese
      population.

PMID- 21866217
TI  - Letters to the editor.

PMID- 21866218
TI  - Dual-Band Miniaturized Patch Antennas for Microwave Breast Imaging.
AB  - We present a miniaturized, dual-band patch antenna array element that is designed
      for use in a 3-D microwave tomography system for breast imaging. Dual-band
      operation is achieved by manipulating the fundamental resonant mode of the patch
      antenna and one of its higher-order modes. Miniaturization and tuning of the
      resonant frequencies are achieved by loading the antenna with non-radiating slots
      at strategic locations along the patch. This results in a compact, dual-band
      antenna with symmetric radiation patterns and similar radiation characteristics
      at both bands of operation. The performance of the antenna in a biocompatible
      immersion medium is verified experimentally.

PMID- 21866219
TI  - Uncovering Knowledge of Core Syntactic and Semantic Principles in Individuals
      With Williams Syndrome.
AB  - We investigate knowledge of core syntactic and semantic principles in individuals
      with Williams Syndrome (WS). Our study focuses on the logico-syntactic properties
      of negation and disjunction (or) and tests knowledge of (a) core syntactic
      relations (scope and c-command), (b) core semantic relations (entailment
      relations and DeMorgan's laws of propositional logic), and (c) the relationship
      between (a) and (b). We examine the performance of individuals with WS, children
      matched for mental age (MA), and typical adult native speakers of English.
      Performance on all conditions suggests that knowledge of (a-c) is present and
      engaged in all three groups. Results also indicate slightly depressed performance
      on (c) for the WS group, compared to MA, consistent with limitation in processing
      resources. Implications of these results for competing accounts of language
      development in WS, as well as for the relevance of WS to the study of cognitive
      architecture and development are discussed.

PMID- 21866220
TI  - Variation of Surface Charge along the Surface of Wool Fibers Assessed by High
      Resolution Force Spectroscopy.
AB  - In this study, we have mapped the surface charge of wool fibers using chemically
      specific high-resolution force spectroscopy in order to better understand the
      dispersion of amino acids in relation to fiber morphology. The inter-surface
      forces between standard atomic force microscopy (AFM) probe tips (tip radius ~ 50
      nm) functionalized with COOH and NH(3) terminated alkanethiol self assembling
      monolayers and the wool surface were used to estimate the surface charge per unit
      area using linear Poisson-Boltzmann-based electrostatic double layer theory. The
      positional measurement of nano-scale surface charge showed a correlation between
      the surface charge and fiber morphology, indicated that basic amino acids are
      located near the scale edges.

PMID- 21866221
TI  - Determinants of appetite ratings: the role of age, gender, BMI, physical
      activity, smoking habits, and diet/weight concern.
AB  - BACKGROUND: Appetite measures are often recorded by visual analogue scales (VAS),
      and are assumed to reflect central nervous system (CNS) perceptions and
      sensations. However, little is known about how physiological, psychological,
      social, and cultural factors influence VAS. OBJECTIVE: To investigate whether
      age, gender, body mass index (BMI), smoking habits, physical activity, diet
      behaviour, and menstruation cycle are determinants of appetite ratings. DESIGN:
      We investigated appetite ratings in different groups of a population during a
      single meal test, including 178 healthy women (98) and men (80), aged 20-60 years
      with a BMI of 18.5-35.0 kg/m(2). Subjects consumed an evening meal composed to
      meet individual requirements of energy content and recommendations regarding
      macronutrient composition. Before and every half hour until 3 hours after the
      meal, subjects filled out VAS for satiety, fullness, hunger, and prospective food
      intake. They also filled in a questionnaire on eating/slimming behaviour.
      RESULTS: Multiple linear regression analyses showed that gender and age were the
      most powerful predictors of postprandial satiety (p<0.001, adj. R(2)=0.19) and
      hunger (p<0.001, adj. R(2)=0.15). Repeated measures general linear model (GLM)
      analyses revealed that women felt more satisfied than men (p<0.001) and older
      subjects felt more satisfied than younger (p<0.01). Furthermore, light/no
      exercisers felt more satisfied and less hungry than hard/moderate exercisers
      (p<0.05), but these differences disappeared after adjusting for age and gender.
      Smokers rated their prospective consumption lower than non-smokers (p<005) and
      women in the ovulation phase felt less hungry than women in the menstruation
      phase (p<005). Neither BMI nor diet/weight concern were significantly associated
      with appetite ratings. CONCLUSIONS: Appetite ratings differed according to age,
      gender, and physical activity and to a lesser degree for smoking habits and
      menstruation cycle. Appetite ratings were not influenced by BMI and diet/weight
      concern. These factors should be considered when planning studies and analysing
      data concerning appetite sensations.

PMID- 21866222
TI  - Impacts of flood on health: epidemiologic evidence from Hanoi, Vietnam.
AB  - BACKGROUND: Vietnam is one of the most disaster-prone countries in the world. The
      country suffers from many kinds of natural disasters, of which the most common
      and serious one is flooding. Long and heavy rainfall during the last days of
      October and the first week of November 2008 resulted in a devastating flood
      unseen for over three decades in the capital city of Hanoi. It caused a
      substantial health impact on residents in and around the city and compromised the
      capacity of local health services. OBJECTIVE: The aim of this study is to
      ascertain the vulnerability and health impacts of the devastating flood in Hanoi
      by identifying the differences in mortality, injuries, and morbidity patterns
      (dengue, pink eye, dermatitis, psychological problems, and hypertension) between
      flood affected and non-affected households. DESIGN: A cross-sectional study was
      carried out involving 871 households in four selected communes (two heavily flood
      affected and two comparatively less affected) from two severely flooded districts
      of Hanoi. Participants were interviewed and information collected on the social,
      economic, and health impacts of the devastation within 1 month after the flood.
      RESULTS: The self-reported number of deaths and injuries reported in this study
      within 1 month after the heavy rainfall were a bit higher in severely affected
      communes as compared to that of the less affected communes of our study. The
      findings showed higher incidences of dengue fever, pink eye, dermatitis, and
      psychological problems in communes severely affected by flood as compared to that
      of the controlled communes. CONCLUSIONS: For people in flood prone areas (at risk
      for flooding), flood prevention and mitigation strategies need to be seriously
      thought through and acted upon, as these people are exposed to greater health
      problems such as psychological issues and communicable diseases such as pink eye
      or dermatitis.

PMID- 21866223
TI  - Disability and health-related rehabilitation in international disaster relief.
AB  - BACKGROUND: Natural disasters result in significant numbers of disabling
      impairments. Paradoxically, however, the traditional health system response to
      natural disasters largely neglects health-related rehabilitation as a strategic
      intervention. OBJECTIVES: To examine the role of health-related rehabilitation in
      natural disaster relief along three lines of inquiry: (1) epidemiology of injury
      and disability, (2) impact on health and rehabilitation systems, and (3) the
      assessment and measurement of disability. DESIGN: Qualitative literature review
      and secondary data analysis. RESULTS: Absolute numbers of injuries as well as
      injury to death ratios in natural disasters have increased significantly over the
      last 40 years. Major impairments requiring health-related rehabilitation include
      amputations, traumatic brain injuries, spinal cord injuries (SCI), and long bone
      fractures. Studies show that persons with pre-existing disabilities are more
      likely to die in a natural disaster. Lack of health-related rehabilitation in
      natural disaster relief may result in additional burdening of the health system
      capacity, exacerbating baseline weak rehabilitation and health system
      infrastructure. Little scientific evidence on the effectiveness of health-related
      rehabilitation interventions following natural disaster exists, however. Although
      systematic assessment and measurement of disability after a natural disaster is
      currently lacking, new approaches have been suggested. CONCLUSION: Health-related
      rehabilitation potentially results in decreased morbidity due to disabling
      injuries sustained during a natural disaster and is, therefore, an essential
      component of the medical response by the host and international communities.
      Significant systematic challenges to effective delivery of rehabilitation
      interventions during disaster include a lack of trained responders as well as a
      lack of medical recordkeeping, data collection, and established outcome measures.
      Additional development of health-related rehabilitation following natural
      disaster is urgently required.

PMID- 21866225
TI  - The effect of propranolol and midazolam on the reconsolidation of a morphine
      place preference in chronically treated rats.
AB  - A stable memory can be disrupted if amnestic treatment is applied in conjunction
      with memory reactivation. Recent findings in the conditioned place preference
      (CPP) model suggest that blocking reconsolidation attenuates the ability of
      environmental cues to induce craving and relapse in drug addicts, but the impact
      of prior physical dependence has not been described. We examined the effect of
      post-reactivation amnestic treatment on reconsolidation of a CPP for morphine, in
      animals naive to morphine, under chronic morphine experience or abstinent.
      Chronic morphine experience was induced by escalating doses of morphine from 10
      mg/kg/day (s.c.), and maintained on 30 mg/kg/day during the course of
      conditioning and reactivation procedures, or conditioning alone. Naive and
      morphine-experienced animals were trained in a three-compartment apparatus by
      four morphine (5 mg/kg, s.c.) and four saline experiences paired with either of
      two large conditioning compartments. The memory was then reactivated by a CPP
      test, and immediately afterward animals received an injection of the beta
      adrenergic antagonist propranolol (10 mg/kg, s.c.), the GABAa agonist midazolam
      (1 mg/kg, i.p.), or saline. Morphine-naive rats received only a single
      reconsolidation-blocking treatment (Experiment 1), while chronic morphine rats
      were given eight reactivation sessions each followed by amnestic treatment,
      either before (Experiment 2) or after 10 days of withdrawal (Experiment 3).
      Propranolol and midazolam disrupted reconsolidation in morphine-naive rats, but
      failed to disrupt the CPP when rats were trained under chronic morphine
      treatment, even if they were recovered from chronic opiate exposure before
      reactivation. In fact, propranolol increased the preference for the drug-paired
      context in animals trained while maintained on chronic morphine. Midazolam had
      little effect. Morphine experience may produce neurochemical changes which alter
      memory storage processes and reduce the impact of amnestic treatments on
      reconsolidation.

PMID- 21866226
TI  - Linking behavioral and neurophysiological indicators of perceptual tuning to
      language.
AB  - Little is known about the neural mechanisms that underlie tuning to the native
      language(s) in early infancy. Here we review language tuning through the lens of
      type and amount of language experience and introduce a new manner in which to
      conceptualize the phenomenon of language tuning: the relative speed of tuning
      hypothesis. This hypothesis has as its goal a characterization of the unique time
      course of the tuning process, given the different components (e.g., phonology,
      prosody, syntax, semantics) of one or more languages as they become available to
      infants, and biologically based maturational constraints. In this review, we
      first examine the established behavioral findings and integrate more recent
      neurophysiological data on neonatal development, which together demonstrate
      evidence of early language tuning given differential language exposure even in
      utero. Next, we examine traditional accounts of sensitive and critical periods to
      determine how these constructs complement current data on the neural mechanisms
      underlying language tuning. We then synthesize the extant infant behavioral and
      neurophysiological data on monolingual, bilingual, and sensory deprived tuning,
      thereby scrutinizing the effect of these three different language profiles on the
      specific timing, progression, and outcome of language tuning. Finally, we discuss
      future directions researchers might pursue to further understand this aspect of
      language development, advocating our relative speed of tuning hypothesis as a
      useful framework for conceptualizing the complex process by which language
      experience works together with biological constraints to shape language
      development.

PMID- 21866224
TI  - The corticostriatal and corticosubthalamic pathways: two entries, one target. So
      what?
AB  - The basal ganglia receive cortical inputs through two main stations - the
      striatum and the subthalamic nucleus (STN). The information flowing along the
      corticostriatal system is transmitted to the basal ganglia circuitry via the
      "direct and indirect" striatofugal pathways, while information that flows through
      the STN is transmitted along the so-called "hyperdirect" pathway. The functional
      significance of this dual entry system is not clear. Although the corticostriatal
      system has been thoroughly characterized anatomically and electrophysiologically,
      such is not the case for the corticosubthalamic system. In order to provide
      further insights into the intricacy of this complex anatomical organization, this
      review examines and compares the anatomical and functional organization of the
      corticostriatal and corticosubthalamic systems, and highlights some key issues
      that must be addressed to better understand the mechanisms by which these two
      neural systems may interact to regulate basal ganglia functions and dysfunctions.

PMID- 21866227
TI  - Gender Differences in Personality across the Ten Aspects of the Big Five.
AB  - This paper investigates gender differences in personality traits, both at the
      level of the Big Five and at the sublevel of two aspects within each Big Five
      domain. Replicating previous findings, women reported higher Big Five
      Extraversion, Agreeableness, and Neuroticism scores than men. However, more
      extensive gender differences were found at the level of the aspects, with
      significant gender differences appearing in both aspects of every Big Five trait.
      For Extraversion, Openness, and Conscientiousness, the gender differences were
      found to diverge at the aspect level, rendering them either small or undetectable
      at the Big Five level. These findings clarify the nature of gender differences in
      personality and highlight the utility of measuring personality at the aspect
      level.

PMID- 21866229
TI  - Effect of regular gum chewing on levels of anxiety, mood, and fatigue in healthy
      young adults.
AB  - INTRODUCTION: The effect of regular gum chewing on psychological status is
      unknown. The purpose of this study was to examine the effect of gum chewing for
      fourteen days on psychological status and physical and mental fatigue in healthy
      young adults. METHODS: We assigned 50 volunteers randomly to an intervention
      group (n = 26) and a control group (n = 24). Participants in the intervention
      group were requested to chew the gum twice per a day for fourteen days. The
      volunteers were required to complete a questionnaire related to lifestyle for
      baseline assessment. The State-Trait Anxiety Inventory (STAI), the Profile of
      Mood State (POMS), the World Health Organization Quality of Life 26, and
      assessment of physical and mental fatigue by visual analog scale were used at
      baseline, 2 weeks (after intervention), and 4 weeks (follow-up). RESULTS: At 2
      weeks, the score of state anxiety was significantly lower in the intervention
      group than the control group. The intervention participants' scores of depression
      dejection, fatigue and confusion in POMS were better than the control group
      scores. Mental fatigue were also relieved after the intervention. At 4 weeks,
      there were no significant differences between both groups. CONCLUSION: Fourteen
      days' gum chewing may improve the levels of anxiety, mood and fatigue.

PMID- 21866230
TI  - Differences between early and late onset adult depression.
AB  - BACKGROUND: It is unclear, whether age-of-onset identifies subgroups of
      depression. AIM: To assess the clinical presentation of depression with onset in
      the early adult age (18-30 years) as compared to depression with later onset (31
      70 years). METHOD: A total number of 301 patients with first episode depression
      were systematically recruited. Characteristics including psychiatric co
      morbidity, personality disorders and traits, stressful life events prior to
      onset, family history, and treatment outcome were assessed by structured
      interviews and compared by chi-square tests for categorical data, t-tests for
      continuous parametric data and Mann-Whitney U-test for continuous nonparametric
      data. Logistic and multiple regression analyses were used to adjust the analyses
      for potentially confounding variables. RESULTS: Patients with early onset of
      depression were characterised by a higher prevalence of co-morbid personality
      disorders, higher levels of neuroticism, and a lower prevalence of stressful life
      events preceding onset compared to patients with later age-of-onset. There were
      no differences in severity of the depressive episode, treatment outcome or family
      loading of psychiatric illness. CONCLUSION: Early adult onset of depression is
      associated with co-morbid personality deviances, whereas late onset is associated
      with environmental risk factors.

PMID- 21866231
TI  - Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in
      Patients with Failing Fontan Physiology.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of sildenafil
      in patients with failing Fontan physiology.  DESIGN: A retrospective chart review
      was performed to compare history and available data in patients with Fontan
      circulations before and after starting sildenafil. The paired and unpaired
      Student's t-tests were used for statistical analyses.  PATIENTS: Six patients at
      our institution with Fontan physiology, persistent symptoms of cyanosis or
      effusion, and poor hemodynamics as measured in the catheterization laboratory
      were placed on sildenafil. One patient was not included in the analysis because
      of insufficient length of treatment. All patients had symptoms of failing Fontan
      hemodynamics with either persistent cyanosis or effusions. In this group, the
      mean pulmonary artery pressure was greater than 15 mm Hg (17.4 +/- 1.5 mm Hg)
      with mean estimated pulmonary vascular resistance of 3.5 +/- 1.0 Wood units *
      m(2) prior to starting sildenafil.  RESULTS: Sildenafil significantly increased
      the systemic arterial oxyhemoglobin saturation in this group (82.8 +/- 7.3% pre
      treatment vs. 91.0 +/- 5.5% post-treatment, P = .017). In the four out of five
      patients who have had follow-up catheterizations, there was a significant
      decrease in pulmonary artery pressure (17.4 +/- 1.5 mm Hg pre-treatment vs. 13.8
      +/- 2.1 mm Hg post-treatment, P = .018) and in estimated pulmonary vascular
      resistance pre- and post-sildenafil treatment (3.5 +/- 1.0 Wood units * m(2) pre
      treatment vs. 2.0 +/- 0.4 Wood units * m(2) post-treatment, P = .031). 
      CONCLUSIONS: Sildenafil may be a useful adjunct to therapy in patients with
      failing Fontan physiology likely through its function as a pulmonary vasodilator.

PMID- 21866232
TI  - Eliciting reflections on caring theory in elderly caring practice.
AB  - Caring theories are the description and conceptualization of the care that is
      given in caring practise by nurses and other professional caregivers with the aim
      of verbalizing and communicating caring phenomena. Intermittently, a theory 
      practice gap is given expression- that theory does not go along with clinical
      practice in caring.The aim of this study was an investigation into the possible
      disparity between theory and practice in caring by analysing nurses' lived
      experience of the understanding of caring theory in practice in the context of
      municipal elderly care.Hermeneutical phenomenology was the research approach used
      to explore the lived experience of caring science theories in caring practice
      from the perspective of 12 nurses working in municipal care for elderly.The
      findings shows that the nurses Impulsively described their experience of
      detachment to caring theory, but when describing their caring intentions, the
      relationship to theory became apparent, and even confirmed their practice. As
      such, a seedbed exists for caring theory to be reflected on and cultivated in
      caring praxis. However, as the nurses describe, the caring theory must be
      sensitive enough for the nursing practitioners to accept.The gap revealed itself
      on an organisational level, as the nurses' commission in municipal care did not
      correspond with their caring intention.We believe it is important to seriously
      consider what we want to achieve as a caring profession. We have to reflect on
      our responsibility as culture carriers and knowledge developers. We must make the
      disparate forces of intention and organisation become one intertwining force.

PMID- 21866233
TI  - Life threatening retroperitoneal haemorrhage due to therapeutic fondaparinux.
AB  - We report the case of a patient with pulmonary embolism, treated with
      fondaparinux as bridging therapy until therapeutic levels were achieved on
      warfarin, who developed a non-traumatic massive retroperitoneal haematoma
      requiring substantial resuscitation with blood products and arterial
      embolisation. To our knowledge, this condition has not been reported with
      therapeutic doses of fondaparinux. Our patient, however, may have been more
      predisposed to bleeding due to the unpredictable pharmacokinetics of fondaparinux
      secondary to his morbid obesity, reduced clearance of the drug due to renal
      insufficiency and concomitant treatment with low dose aspirin and warfarin.
      Another consideration was the lack of a specific reversing agent for fondaparinux
      in the setting of a life threatening haemorrhage.

PMID- 21866234
TI  - Furuncular myiasis.

PMID- 21866235
TI  - Localised primary amyloidosis of the urinary bladder: case series of two
      patients.
AB  - Isolated amyloidosis of the lower urinary tract is rare. This report presents
      localised primary amyloidosis of the urinary bladder as a rare cause of
      macroscopic haematuria. Treatment of bladder amyloidosis mainly consists of
      controlling the haematuria. For small localised lesions, the favoured approach is
      transurethral resection (TUR) of the lesion.

PMID- 21866236
TI  - Eruptive xanthomas with Koebner phenomenon, type 1 diabetes mellitus,
      hypertriglyceridaemia and hypertension in a 41-year-old man.

PMID- 21866237
TI  - Off-pump coronary artery surgery in a patient with essential thrombocythaemia:
      two life-threatening complications in the same patient.
AB  - Essential thrombocythaemia (ET) is a rare chronic myeloproliferative disease
      characterised by persistent thrombocytosis. Cerebral, myocardial and peripheral
      thrombosis are frequently seen complications, but bleeding and venous thrombosis
      are more rare. Here, a case of essential thrombocythaemia complicated by cerebral
      and myocardial thrombosis is presented. The patient's platelet count was
      680*10(9)/litre on admission. Electrocardiogram showed a slight ST elevation in
      leads V1 to V4. A coronary angiography was performed and it revealed a severe
      stenosis of the left anterior descending artery. The patient had a successful off
      pump coronary artery bypass grafting surgery. After the operation the platelet
      count was 390*10(9)/litre. The patient received hydroxyurea and aspirin treatment
      preoperatively and continued postoperatively. ET is a rare myeloproliferative
      disease; its complications are also rare, but the occurrence of two life
      threatening complications in the same patient is rarer still. Further
      investigations are needed to determine the risk stratification for patients with
      ET undergoing cardiac surgery.

PMID- 21866228
TI  - Carbon metabolic pathways in phototrophic bacteria and their broader evolutionary
      implications.
AB  - Photosynthesis is the biological process that converts solar energy to biomass,
      bio-products, and biofuel. It is the only major natural solar energy storage
      mechanism on Earth. To satisfy the increased demand for sustainable energy
      sources and identify the mechanism of photosynthetic carbon assimilation, which
      is one of the bottlenecks in photosynthesis, it is essential to understand the
      process of solar energy storage and associated carbon metabolism in
      photosynthetic organisms. Researchers have employed physiological studies,
      microbiological chemistry, enzyme assays, genome sequencing, transcriptomics, and
      (13)C-based metabolomics/fluxomics to investigate central carbon metabolism and
      enzymes that operate in phototrophs. In this report, we review diverse CO(2)
      assimilation pathways, acetate assimilation, carbohydrate catabolism, the
      tricarboxylic acid cycle and some key, and/or unconventional enzymes in central
      carbon metabolism of phototrophic microorganisms. We also discuss the reducing
      equivalent flow during photoautotrophic and photoheterotrophic growth,
      evolutionary links in the central carbon metabolic network, and correlations
      between photosynthetic and non-photosynthetic organisms. Considering the
      metabolic versatility in these fascinating and diverse photosynthetic bacteria,
      many essential questions in their central carbon metabolism still remain to be
      addressed.

PMID- 21866238
TI  - Epiploic appendagitis.
AB  - A 25-year-old female presented to the emergency department (ED) with a 1-day
      history of crampy left iliac fossa (LIF) abdominal pain. It was associated with
      both nausea and vomiting. On examination she was tender in the LIF with some
      guarding. Her observations were satisfactory and she was apyrexial. Urine
      dipstick and pregnancy stick were negative. The case was a diagnostic quandary.
      On ultrasound scan (USS) no acute gynaecological problems were found. Computed
      tomography (CT) of the abdomen showed epiploic appendagitis. This was managed
      conservatively with analgesia and antibiotics and the patient was discharged home
      pain free. She was followed up in the general surgical clinic 1 week later where
      she continued to be symptom free. She was discharged from general surgical care.

PMID- 21866239
TI  - 1st International Conference Faculty Development in the health professions.
      Toronto (Canada) May, 10th -13th, 2011.

PMID- 21866240
TI  - Interactive e-learning courses in human genetics: usage and evaluation by science
      and medical students at the faculty of medicin.
AB  - INTRODUCTION: This study presents our online-teaching material within the k-MED
      project (Knowledge in Medical Education) at the university of Marburg. It is
      currently organized in five e-learning modules: cytogenetics, chromosomal
      aberrations, formal genetics, fundamentals of molecular diagnostics, and
      congenital abnormalities and syndromes. These are basic courses intended to do
      the educational groundwork, which will enable academic teachers to concentrate on
      more sophisticated topics during their lectures. METHODS: The e-learning modules
      have been offered to a large group of about 3300 students during four years at
      the Faculty of Medicine in Marburg. The group consists of science students (human
      biology) and medical students in the preclinical or the clinical period,
      respectively. Participants were surveyed on acceptance by evaluating user
      tracking data and questionnaires. RESULTS AND CONCLUSION: Analysis of the
      evaluation data proofs the broad acceptance of the e-learning modules during
      eight semesters. The courses are in stable or even increasing use from winter
      term 2005/06 until spring term 2009. CONCLUSION: Our e-learning-model is broadly
      accepted among students with different levels of knowledge at the Faculty of
      Medicine in Marburg. If the e-learning courses are maintained thoroughly, minor
      adaptations can increase acceptance and usage even furthermore. Their use should
      be extended to the medical education of technical assistances and nurses, who
      work in the field of human genetics.

PMID- 21866241
TI  - Heading in the same direction: the skills-lab workshops Marburg-Goettingen - A
      field report.
AB  - HISTORY: After the initiation of skills-labs in Marburg and Goettingen the peer
      teaching students of both institutions saw a need for communication and
      cooperation. The primary goal of these 'skills-lab workshops' was the exchange of
      already existing ideas for extracurricular peer-teaching, the development of new
      tutorials and long-term cooperation between the institutions. METHODS: In January
      of 2010 the 1(st) 'skills-lab workshop' Marburg-Goettingen was held at the
      'Marburg's Interdisciplinary skills-lab' (Maris, since 10/2008). The 2(nd)
      workshop was held at the 'Student's trainings center of medical practice and
      simulation' (STAPS, since 10/2009) in Goettingen in October of 2010. RESULTS AND
      CONCLUSION: Especially younger skills-labs can profit from an exchange with a
      more established Institution. Cooperations like these are the foundation for
      future exchange of ideas for new peer-teachings and the continuous improvement or
      a transfer of existing peer-teachings for skills-labs. We recommend bilateral
      exchanges like this to other and especially to new skills-labs.

PMID- 21866242
TI  - Differential diagnosis in primary care: conception and implementation of a new
      elective seminar - An experience report.
AB  - Primary care is in a unique position to teach the broad spectrum of differential
      diagnoses. We developed and piloted a new elective seminar 'Differential
      Diagnosis in Primary Care'. With the help of simulation patients, training
      models, interactive small group work, and short lectures we addressed common
      complaints presented in the daily routine of primary care like vertigo, dyspnoea,
      chest or abdominal pain. We put a special focus on the diagnostic accuracy of
      history and physical examination. The final examination was conducted as an
      objective structured clinical examination.

PMID- 21866243
TI  - Clerkship maturity: does the idea of training clinical skills work?
AB  - BACKGROUND: With the reformed curriculum "4C", the Medical Faculty of the
      University of Cologne has started to systematically plan practical skills
      training, for which Clerkship Maturity is the first step. The key guidelines
      along which the curriculum was development were developed by experts. This
      approach has now been validated. MATERIALS AND METHODS: Both students and
      teachers were asked to fill in a questionnaire regarding preclinical practical
      skills training to confirm the concept of Clerkship Maturity. RESULTS AND
      DISCUSSION: The Cologne training program Clerkship Maturity can be validated
      empirically overall through the activities of the students awaiting the clerkship
      framework and through the evaluation by the medical staff providing the training.
      The subjective ratings of the advantages of the training by the students leave
      room for improvement. Apart from minor improvements to the program, the most
      likely solution providing sustainable results will involve an over-regional
      strategy for establishing skills training planned as part of the curriculum.

PMID- 21866244
TI  - Acceptance of medical training cases as supplement to lectures.
AB  - INTRODUCTION: Medical training cases (virtual patients) are in widespread use for
      student education. Most publications report about development and experiences in
      one course with training cases. In this paper we compare the acceptance of
      different training case courses with different usages deployed as supplement to
      lectures of the medical faculty of Wuerzburg university during a period of three
      semesters. METHODS: The training cases were developed with the authoring tool
      CaseTrain and are available for students via the Moodle-based eLearning platform
      WueCampus at Wuerzburg university. Various data about usage and acceptance is
      automatically collected. RESULTS: From WS (winter semester) 08/09 till WS 09/10
      19 courses with about 200 cases were available. In each semester, about 550
      different medical students from Wurzburg and 50 students from other universities
      processed about 12000 training cases and filled in about 2000 evaluation forms.
      In different courses, the usage varied between less than 50 and more than 5000
      processed cases. DISCUSSION: Although students demand training cases as
      supplement to all lectures, the data show that the usage does not primarily
      depend on the quality of the available training cases. Instead, the training
      cases of nearly all case collections were processed extremely often shortly
      before the examination. It shows that the degree of usage depends primarily on
      the perceived relevance of the training cases for the examination.

PMID- 21866245
TI  - Web-based training in German university eye hospitals - Education 2.0?
AB  - PURPOSE: To analyse web-based training in ophthalmology offered by German
      university eye hospitals. METHODS: In January 2010 the websites of all 36 German
      university hospitals were searched for information provided for visitors,
      students and doctors alike. We evaluated the offer in terms of quantity and
      quality. RESULTS: All websites could be accessed at the time of the study. 28
      pages provided information for students and doctors, one page only for students,
      three exclusively for doctors. Four pages didn't offer any information for these
      target groups. The websites offered information on events like congresses or
      students curricular education, there were also material for download for these
      events or for other purposes. We found complex e-learning-platforms on 9 pages.
      These dealt with special ophthalmological topics in a didactic arrangement. In
      spite of the extensive possibilities offered by the technology of Web 2.0, many
      conceivable tools were only rarely made available. It was not always possible to
      determine if the information provided was up-to-date, very often the last
      actualization of the content was long ago. On one page the date for the last
      change was stated as 2004. CONCLUSION: Currently there are 9 functional e
      learning-applications offered by German university eye hospitals. Two additional
      hospitals present links to a project of the German Ophthalmological Society.
      There was a considerable variation in quantity and quality. No website made use
      of crediting successful studying, e.g. with CME-points or OSCE-credits. All
      German university eye hospitals present themselves in the World Wide Web.
      However, the lack of modern, technical as well as didactical state-of-the-art
      learning applications is alarming as it leaves an essential medium of today's
      communication unused.

PMID- 21866246
TI  - Reliability of a science admission test (HAM-Nat) at Hamburg medical school.
AB  - OBJECTIVE: The University Hospital in Hamburg (UKE) started to develop a test of
      knowledge in natural sciences for admission to medical school in 2005 (Hamburger
      Auswahlverfahren fur Medizinische Studiengange, Naturwissenschaftsteil, HAM-Nat).
      This study is a step towards establishing the HAM-Nat. We are investigating
      parallel forms reliability, the effect of a crash course in chemistry on test
      results, and correlations of HAM-Nat test results with a test of scientific
      reasoning (similar to a subtest of the "Test for Medical Studies", TMS). METHODS:
      316 first-year students participated in the study in 2007. They completed
      different versions of the HAM-Nat test which consisted of items that had already
      been used (HN2006) and new items (HN2007). Four weeks later half of the
      participants were tested on the HN2007 version of the HAM-Nat again, while the
      other half completed the test of scientific reasoning. Within this four week
      interval students were offered a five day chemistry course. RESULTS: Parallel
      forms reliability for four different test versions ranged from r(tt)=.53 to
      r(tt)=.67. The retest reliabilities of the HN2007 halves were r(tt)=.54 and r(tt
      )=.61. Correlations of the two HAM-Nat versions with the test of scientific
      reasoning were r=.34 und r=.21. The crash course in chemistry had no effect on
      HAM-Nat scores. CONCLUSIONS: The results suggest that further versions of the
      test of natural sciences will not easily conform to the standards of internal
      consistency, parallel-forms reliability and retest reliability. Much care has to
      be taken in order to assemble items which could be used interchangeably for the
      construction of new test versions. The test of scientific reasoning and the HAM
      Nat are tapping different constructs. Participation in a chemistry course did not
      improve students' achievement, probably because the content of the course was not
      coordinated with the test and many students lacked of motivation to do well in
      the second test.

PMID- 21866247
TI  - Ready for the OR? - Clinical anatomy and basic surgical skills for students in
      their preclinical education.
AB  - Medical students' first experience in the operating theatre often takes place
      during their electives and is therefore separated from the university's medical
      curriculum. In the winter term 2009/10, the Institute of Anatomy and Cell Biology
      at the University of Ulm implemented an elective called "Ready for the OR" for
      2nd year medical students participating in the dissection course. We attempted to
      improve learning motivation and examination results by transferring anatomical
      knowledge into a surgical setting and teaching basic surgical skills in
      preparation of the students' first participation in the OR. Out of 69 online
      applicants, 50 students were randomly assigned to the Intervention Group (FOP) or
      the Control Group. In 5 teaching session students learned skills like scrubbing,
      stitching or the identification of frequently used surgical instruments.
      Furthermore, students visited five surgical interventions which were demonstrated
      by surgical colleagues on donated bodies that have been embalmed using the Thiel
      technique. The teaching sessions took place in the institute's newly built
      "Theatrum Anatomicum" for an ideal simulation of a surgical setting. The learning
      outcomes were verified by OSPE. In a pilot study, an intervention group and a
      control group were compared concerning their examination results in the
      dissection course and their learning motivation through standardized SELLMO-test
      for students. Participants gained OSPE results between 60.5 and 92% of the
      maximum score. "Ready for the OR" was successfully implemented and judged an
      excellent add-on to anatomy teaching by the participants. However, we could not
      prove a significant difference in learning motivation or examination results.
      Future studies should focus on the learning orientation, the course's long-term
      learning effects and the participants' behavior in a real surgery setting.

PMID- 21866248
TI  - JATSPack and JATSPAN, a packaging format and infrastructure for the NLM/NISO
      Journal Archiving Tag Suite (JATS).
AB  - The NISO Journal Archiving Tag Suite (JATS, formerly known as 'the NLM DTD') is a
      common format used in publication of scientific literature. JATSPack, a proposal
      based on the new EXPath Packaging System, provides a way to package schema
      customizations and software libraries associated with any of the JATS schemas,
      thus making it easier for developers to distribute JATS-related resources and
      easier for users to acquire, install, and use them. JATSPAN (the JATSPack Archive
      Network) is a website allowing users to share and collaborate on JATSPacks. A
      client-side command line tool, jatspan, interacts with the site and eases the
      task of maintaining local repositories of JATSPacks.

PMID- 21866250
TI  - Nonmuscle myosin II regulates migration but not contraction in rat hepatic
      stellate cells.
AB  - AIM: To identify and characterize the function of nonmuscle myosin II (NMM II)
      isoforms in primary rat hepatic stellate cells (HSCs). METHODS: Primary HSCs were
      isolated from male Sprague-Dawley rats by pronase/collagenase digestion. Total
      RNA and protein were harvested from quiescent and culture-activated HSCs. NMM II
      isoform (II-A, II-B and II-C) gene and protein expression were measured by
      RealTime polymerase chain reaction and Western blot analyses respectively. NMM II
      protein localization was visualized in vitro using immunocytochemical analysis.
      For in vivo assessment, liver tissue was harvested from bile duct-ligated (BDL)
      rats and NMM IIisoform expression determined by immunohistochemistry. Using a
      selective myosin II inhibitor and siRNA-mediated knockdown of each isoform, NMM
      II functionality in primary rat HSCs was determined by contraction and migration
      assays. RESULTS: NMM II-A and II-B mRNA expression was increased in culture
      activated HSCs (Day 14) with significant increases seen in all pair-wise
      comparisons (II-A: 12.67 +/- 0.99 (quiescent) vs 17.36 +/- 0.78 (Day 14), P <
      0.05; II-B: 4.94 +/- 0.62 (quiescent) vs 13.90 +/-0.85 (Day 14), P < 0.001).
      Protein expression exhibited similar expression patterns (II-A: 1.87 +/- 2.50
      (quiescent) vs 58.64 +/- 8.76 (Day 14), P < 0.05; II-B: 1.17 +/- 1.93 (quiescent)
      vs 103.71 +/- 21.73 (Day 14), P < 0.05). No significant differences were observed
      in NMM II-C mRNA and protein expression between quiescent and activated HSCs. In
      culture-activated HSCs, NMM II-A and II-B merged with F-actin at the cellular
      periphery and throughout cytoplasm respectively. In vitro studies showed
      increased expression of NMM II-B in HSCs activated by BDL compared to sham
      operated animals. There were no apparent increases of NMM II-A and II-C protein
      expression in HSCs during hepatic BDL injury. To determine the contribution of
      NMM II-A and II-B to migration and contraction, NMM II-A and II-B expression were
      downregulated with siRNA. NMM II-A and/or II-B siRNA inhibited HSC migration by
      approximately 25% compared to scramble siRNA-treated cells. Conversely, siRNA
      mediated NMM II-A and II-B inhibition had no significant effect on HSC
      contraction; however, contraction was inhibited with the myosin II inhibitor,
      blebbistatin (38.7% +/- 1.9%). CONCLUSION: Increased expression of NMM II-A and
      II-B regulates HSC migration, while other myosin IIclasses likely modulate
      contraction, contributing to development and severity of liver fibrosis.

PMID- 21866249
TI  - A survey on herbal management of hepatocellular carcinoma.
AB  - In this review we outline the different mechanisms mediating
      hepatocarcinogenesis. We also discuss possible targets of bioactive herbal agents
      at different stages of hepatocarcinogenesis and highlight their role at each
      individual stage. We gathered information on the most common herbal prescriptions
      and extracts thought to be useful in prevention or sensitization for chemotherapy
      in management of hepatocellular carcinoma (HCC). The value of this topic may seem
      questionable compared to the promise offered for HCC management by chemotherapy
      and radiation. However, we would recommend the use of herbal preparations not as
      alternatives to common chemo /and or radiotherapy, but rather for prevention
      among at-risk individuals, given that drug/herb interactions are still in need of
      extensive clarification. The bioactive constituents of various herbs seem to be
      promising targets for isolation, cancer activity screening and clinical
      evaluation. Finally, herbal preparations may offer a cost effective protective
      alternative to individuals known to have a high risk for HCC and possibly other
      cancers, through maintaining cell integrity, reversing oxidative stress and
      modulating different molecular pathways in preventing carcinogenesis.

PMID- 21866251
TI  - An extended treatment protocol with pegylated interferon and ribavirin for
      hepatitis C recurrence after liver transplantation.
AB  - AIM: To evaluate the efficacy and tolerability of an extended treatment protocol
      and to determine the predictors of sustained virological response (SVR) after
      liver transplantation (LT). METHODS: Between August 2005 and November 2008,
      patients with recurrent hepatitis C virus (HCV) after LT were selected for
      treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2
      fibrosis. All patients were to receive pegylated interferon (PEG)/regimens
      combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.
      RESULTS: Extended protocol treatment was initiated in thirty patients. Overall,
      73% had end of treatment response and 60% had SVR. Nineteen patients completed
      treatment per protocol, of them, sixteen (84%) had end of treatment response, and
      fourteen (74%) achieved SVR. Both early virological response and 24-week
      virological response were individually associated with SVR but this association
      was not significant on multivariate analysis. Eleven patients (37%) discontinued
      therapy due to adverse effects. Cytopenias were the most common and most severe
      adverse effect, and required frquent growth factor use, dose adjustments and
      treatment cessations. The risk of rejection was not increased. CONCLUSION:
      Recurrent HCV after LT can be safely treated with extended virological response
      guided therpy using PEG/RBV, but requires close monitoring for treatment-related
      adverse effects, particularly cytopenias.

PMID- 21866252
TI  - Mallory-Weiss tear during gastric endoscopic submucosal dissection.
AB  - A 78-year-old woman was referred to our department for treatment of an early
      gastric cancer. Esophagogastroduodenoscopy (EGD) demonstrated a flat elevated
      lesion and a polypoid lesion on the greater curvature of the antrum. Histological
      analysis of, endoscopic biopsy samples taken from these lesions revealed an
      adenocarcinoma and a hyperplastic polyp, respectively. ESD was conducted for
      removal of the lesions. Carbon dioxide (CO(2)) instead of room air was used for
      insufflation, and the patient was adequately sedated without struggling or
      vomiting during the treatment. No significant bleeding from the lesion was
      observed during ESD, but fresh blood was identified endoscopically. Surprisingly,
      a Mallory-Weiss tear with active bleeding was detected on the lesser curvature of
      the gastric corpus. A total of eight hemoclips were applied for hemostasis. Both
      lesions were completely removed en bloc, and no bleeding or perforation developed
      after ESD. Histologically, the first lesion was a papillary carcinoma limited to
      the mucosal layer and without lymphovascular invasion or involvement of the
      surgical margins, while the second lesion was a benign hyperplastic polyp.

PMID- 21866253
TI  - Function directs form of neuronal architecture.

PMID- 21866254
TI  - Trailblazing LIM kinases take the lead in collective tumor cell invasion.
AB  - The spread of tumor cells from primary sites often occurs as associated cell
      collectives. In this form of invasion, the contribution of cells leading the way
      may differ from those that follow. By implication, proteins that regulate the
      actin cytoskeleton, a major driver of cell motility, may have different roles
      depending on whether they are in leading or following cells. The LIM kinases 1
      and 2 (LIMK) phosphorylate and inactivate the filamentous actin severing function
      of cofilin proteins. Using siRNA or pharmacological inhibitors, LIMK was found to
      be required in leading cells of collectively invading tumor cells, or in cancer
      associated stromal fibroblasts, for effective extracellular matrix degradation
      that facilitates three-dimensional invasion. The decreased extracellular matrix
      degrading activities were associated with an inability to form the stable
      filamentous actin structures necessary to make matrix-degrading protrusive
      structures. However, LIMK was not required for cell motility or for path
      following in associated collectives. These findings show that leading and
      following cells in collective invasion have different properties and indicate
      that targeting the activities in leading cells is sufficient to significantly
      inhibit tumor cell invasiveness.

PMID- 21866255
TI  - Watching nuclei move: Insights into how kinesin-1 and dynein function together.
AB  - Moving nuclei to specific intracellular locations is central to many cell and
      developmental processes. However, the molecular mechanisms of nuclear migration
      are poorly understood. We took advantage of the ability to film nuclear migration
      events in Caenorhabditis elegans embryos to gain insights into the mechanisms of
      nuclear migration. Mutations in unc-83 blocked the initiation of nuclear
      migration. UNC-83 recruits kinesin-1 and dynein to the nuclear envelope. Live
      imaging of mutants showed that kinein-1 provides the major force to move nuclei.
      Dynein is responsible to move nuclei backwards or to mediate nuclear rolling to
      by pass cellular roadblocks that impede efficient migration. Live imaging was
      also used to analyze the microtubule network, which is highly polarized and
      dynamic. This detailed mechanism of nuclear migration may be applicable to
      nuclear migration in other systems and for the movement of other large cellular
      cargo.

PMID- 21866256
TI  - Plectin isoforms as organizers of intermediate filament cytoarchitecture.
AB  - Intermediate filaments (IFs) form cytoplamic and nuclear networks that provide
      cells with mechanical strength. Perturbation of this structural support causes
      cell and tissue fragility and accounts for a number of human genetic diseases. In
      recent years, important additional roles, nonmechanical in nature, were ascribed
      to IFs, including regulation of signaling pathways that control survival and
      growth of the cells, and vectorial processes such as protein targeting in
      polarized cellular settings. The cytolinker protein plectin anchors IF networks
      to junctional complexes, the nuclear envelope and cytoplasmic organelles and it
      mediates their cross talk with the actin and tubulin cytoskeleton. These
      functions empower plectin to wield significant influence over IF network
      cytoarchitecture. Moreover, the unusual diversity of plectin isoforms with
      different N termini and a common IF-binding (C-terminal) domain enables these
      isoforms to specifically associate with and thereby bridge IF networks to
      distinct cellular structures. Here we review the evidence for IF cytoarchitecture
      being controlled by specific plectin isoforms in different cell systems,
      including fibroblasts, endothelial cells, lens fibers, lymphocytes, myocytes,
      keratinocytes, neurons and astrocytes, and discuss what impact the absence of
      these isoforms has on IF cytoarchitecture-dependent cellular functions.

PMID- 21866257
TI  - Further insights into cortactin conformational regulation.
AB  - The actin regulatory protein cortactin is involved in multiple signaling pathways
      impinging on the cortical actin cytoskeleton. Cortactin is phosphorylated by
      ERK1/2 and Src family tyrosine kinases, resulting in neuronal Wiskott Aldrich
      Syndrome protein (N-WASp) activation and enhanced actin related protein (Arp)2/3
      mediated actin nucleation. Cortactin migrates as an 80/85 kDa doublet when
      analyzed by SDS-PAGE. Phosphorylation by ERK1/2 is associated with conversion of
      the 80 kDa to the 85 kDa form, postulated to occur by inducing a conformational
      alteration that releases the carboxyl-terminal SH3 domain from autoinhibition.
      Our recent analysis of the 80-85 kDa cortactin "shift" in tumor cells indicates
      that while ERK1/2 phosphorylation is associated with the 85 kDa shift, this
      phosphorylation event is not required for the shift to occur, nor does ERK1/2
      phosphorylation appreciably alter global cortactin confirmation. These data
      indicate that additional factors besides ERK1/2 phosphorylation contribute to
      generating and/or maintaining the activated 85 kDa cortactin form in stimulated
      cells.

PMID- 21866258
TI  - "Chromosome kissing" and modulation of replication termination.
AB  - Previously, inter-chromosomal interactions called "chromosome kissing" have been
      reported to control tissue-specific transcription and cell fate determination.
      Using the fission yeast as a model system we have shown that physiologically
      programmed replication termination is also modulated by chromosome kissing. The
      published report reviewed here shows that a myb-like replication terminator
      protein Reb1 of S. pombe and its cognate binding sites (Ter) are involved in
      chromosome kissing that promotes a cooperative mechanism of replication
      termination. We also suggest that at least one other replication terminator
      protein namely Sap1, which is also an origin binding protein, is likely to be
      involved in a similar mechanism of control not only of fork arrest but also of
      replication initiation and in possible ori-Ter interaction. We discuss the roles
      of chromatin remodeling and other proteins in this novel mechanism of replication
      control.

PMID- 21866259
TI  - Scared stiff: Stabilizing the actin cytoskeleton to stop invading cancer cells in
      their tracks.
AB  - In recent years the concept of plasticity between invasion modes used by
      individual cancer cells has been gaining increasing interest in the field.
      Individually invading tumour cells can be divided into those that use a
      mesenchymal invasion mode, those that use "amoeboid" invasion and those that can
      switch between the two modes. The morphological distinctions between these
      different modes of invasion suggest that the actin cytoskeleton is likely to be a
      major contributor to the plasticity of cancer cell invasion mechanisms. We have
      recently investigated this idea by manipulating expression of Tm5NM1, one isoform
      of the tropomyosin family of actin-associating proteins. In a novel finding, we
      discovered that stabilizing the actin cytoskeleton via elevated expression of
      Tm5NM1 specifically inhibits mesenchymal-type cancer cell invasion, without
      causing transition to "amoeboid" motility-thus stopping the invading cancer cells
      in their tracks. The present perspective discusses our recent data in the context
      of current understanding of invasion plasticity and considers how stabilizing
      actin filaments may inhibit the mesenchymal invasion mode.

PMID- 21866260
TI  - Nanoscopy of cell architecture: The actin-membrane interface.
AB  - It was light microscopy that first revealed the hidden world of bacteria and the
      unit of life the "cell." From these first observations, made in the late 1600s,
      it has been clear that seeing is an important tool in biology. The merging of the
      fields of fluorescence and microscopy created the possibility to see subcellular
      structures and proteins. In the 1990s the use of the confocal microscopes, where
      cells/tissue could be optically sectioned, further improved the resolution of
      object visualization. From this microworld view we now move forward to the
      exciting prospects of the nanoworld view of biology. In this review I propose a
      nanoimaging approach, nanoscopy, which could be used to reveal cell architecture
      at the level of proteins and protein complexes. Nanoscopy includes, the F
      techniques, superresolution microscopy, correlative light and electron microscopy
      and atomic force microscopy. To illustrate the biology that could be investigated
      by nanoscopy we focus on structures formed at the actin-membrane interface. In
      particular, focal adhesions and stress fibres have been analyzed using nanoscopy.
      Many of the proteins present in focal adhesions and stress fibres are shared with
      structures such as filopodia, lamellipodia, endocytic vesicles, actin pedestals
      and invadopodia. It is likely that nanoscopy of cells will reveal mechanistic
      details of biology at the level of individual proteins and protein complexes and
      importantly in a physiological context.

PMID- 21866261
TI  - "Panta rhei": Perpetual cycling of the keratin cytoskeleton.
AB  - The filamentous cytoskeletal systems fulfil seemingly incompatible functions by
      maintaining a stable scaffolding to ensure tissue integrity and simultaneously
      facilitating rapid adaptation to intracellular processes and environmental
      stimuli. This paradox is particularly obvious for the abundant keratin
      intermediate filaments in epithelial tissues. The epidermal keratin cytoskeleton,
      for example, supports the protective and selective barrier function of the skin
      while enabling rapid growth and remodelling in response to physical, chemical and
      microbial challenges. We propose that these dynamic properties are linked to the
      perpetual re-cycling of keratin intermediate filaments that we observe in
      cultured cells. This cycle of assembly and disassembly is independent of protein
      biosynthesis and consists of distinct, temporally and spatially defined steps. In
      this way, the keratin cytoskeleton remains in constant motion but stays intact
      and is also able to restructure rapidly in response to specific regulatory cues
      as is needed, e.g., during division, differentiation and wound healing.

PMID- 21866262
TI  - ESCRT proteins: Double-edged regulators of cellular signaling.
AB  - ESCRT pathway proteins play a key role in sorting ubiquitinated membrane
      receptors towards lysosomes providing an important mechanism for attenuating cell
      surface receptor signaling. However, recent studies point to a positive role of
      ESCRT proteins in signal transduction in multiple species studied under
      physiological and pathological conditions. ESCRT components such as Tsg101 and
      Hrs are overexpressed in human cancers and Tsg101 depletion is detrimental for
      cell proliferation, survival and transformed phenotype of tumor cells. However,
      the mechanisms underlying the positive contributions of ESCRT pathway to surface
      receptor signaling have remained unclear. In a recent study, we showed that
      Tsg101 and Vps4 are essential for translocation of active Src from endosomes to
      focal adhesion and invadopodia, thereby revealing a role of ESCRT pathway in
      promoting Src-mediated migration and invasion. We discuss the implications of
      these and other recent studies which together suggest a role for the ESCRT
      pathway in recycling of endocytic cargo proteins, aside from its role in
      lysosomal targeting, potentially explaining the positive roles of ESCRT proteins
      in signal transduction.

PMID- 21866263
TI  - Functional identity of the gamma tropomyosin gene: Implications for embryonic
      development, reproduction and cell viability.
AB  - The actin filament system is fundamental to cellular functions including
      regulation of shape, motility, cytokinesis, intracellular trafficking and tissue
      organization. Tropomyosins (Tm) are highly conserved components of actin
      filaments which differentially regulate filament stability and function. The
      mammalian Tm family consists of four genes; alphaTm, betaTm, gammaTm and deltaTm.
      Multiple Tm isoforms (>40) are generated by alternative splicing and expression
      of these isoforms is highly regulated during development. In order to further
      identify the role of Tm isoforms during development, we tested the specificity of
      function of products from the gammaTm gene family in mice using a series of gene
      knockouts. Ablation of all gammaTm gene cytoskeletal products results in
      embryonic lethality. Elimination of just two cytoskeletal products from the
      gammaTm gene (NM1,2) resulted in a 50% reduction in embryo viability. It was also
      not possible to generate homozygous knockout ES cells for the targets which
      eliminated or reduced embryo viability in mice. In contrast, homozygous knockout
      ES cells were generated for a different set of isoforms (NM3,5,6,8,9,11) which
      were not required for embryogenesis. We also observed that males hemizygous for
      the knockout of all cytoskeletal products from the gammaTm gene preferentially
      transmitted the minus allele with 80-100% transmission. Since all four Tm genes
      are expressed in early embryos, ES cells and sperm, we conclude that isoforms of
      the gammaTm gene are functionally unique in their role in embryogenesis, ES cell
      viability and sperm function.

PMID- 21866264
TI  - The role of Aurora-A kinase in the Golgi-dependent control of mitotic entry.
AB  - During mitosis, the Golgi complex undergoes a multi-step fragmentation process
      that is instrumental to its correct partitioning into the daughter cells. To
      prepare for this segregation, the Golgi ribbon is initially separated into
      individual stacks during the G2 phase of the cell cycle. Then, at the onset of
      mitosis, these individual stacks are further disassembled into dispersed
      fragments. Inhibition of this Golgi fragmentation step results in a block or
      delay of G2/M transition, depending on the experimental approach. Thus, correct
      segregation of the Golgi complex appears to be monitored by a 'Golgi mitotic
      checkpoint'. Using a microinjection-based approach, we recently identified the
      first target of the Golgi checkpoint, whereby a block of this Golgi fragmentation
      impairs recruitment of the mitotic kinase Aurora-A to, and its activation at, the
      centrosomes. Overexpression of Aurora-A can override this cell cycle block,
      indicating that Aurora-A is a major effector of the Golgi checkpoint. We have
      also shown that this block of Aurora-A recruitment to the centrosomes is not
      mediated by the known mechanisms of regulation of Aurora-A function. Here we
      discuss our findings in relation to the known functions of Aurora-A.

PMID- 21866265
TI  - Formin-g muscle cytoarchitecture.
AB  - Striated muscle cells display an extremely regular assembly of their actin
      cytoskeleton that contributes to the contractile elements, the myofibrils. How
      this assembly is initiated and how these structures are maintained is still
      unclear. We have recently shown that striated muscle expresses a specific isoform
      of the formin protein family member FHOD3, which is characterised by the presence
      of a CK2 phosphorylation site at the C-terminal end of the formin homology domain
      2 (FH2). Phosphorylated muscle FHOD3 displays a different subcellular
      localisation, namely to the myofibrils, and also has increased stability compared
      to un-phosphorylated or non muscle FHOD3. In addition, we could show that muscle
      FHOD3 is involved in myofibril maintenance in cultured cardiomyocytes and that
      its presence dramatically enhances the reconstitution of cardiac actin filaments
      after depolymerisation. Since FHOD3 expression levels and in particular that of
      the muscle isoform are also decreased in different types of cardiomyopathy, we
      postulate a crucial role for this protein in the maintenance of a fully
      functional cardiac cytoarchitecture.

PMID- 21866266
TI  - To branch or not to branch: How PSD-95 regulates dendrites and spines.
AB  - PSD-95, a synaptic scaffolding protein, plays important roles in the regulation
      of dendritic spine morphology and glutamate receptor signaling. We have recently
      shown that PSD-95 also plays an extrasynaptic role during development. PSD-95
      shapes dendrite branching patterns in cultured rat hippocampal neurons by
      altering microtubule dynamics via an association with the microtubule end-binding
      protein-3 (EB3). We discovered that PSD-95 interacts directly with EB3 and that
      the result of this interaction decreases EB3 binding to and EB3 comet lifetime on
      microtubules. This decrease in lifetime also correlates to decreased dendrite
      branching. Here we present an additional effect of PSD-95 overexpression on
      microtubules. Neurons that overexpress PSD-95 show increased distance between
      microtubules in a manner that is not fully dependent on the interaction between
      PSD-95 and EB3. We discuss these new data in the context of the role of PSD-95 in
      shaping the dendritic arbor, and we extend our findings to include a discussion
      of how PSD-95 may guide neurons toward a more mature and synapse-oriented growth
      stage.

PMID- 21866267
TI  - A novel mechanism of microtubule length-dependent force to pull centrosomes
      toward the cell center.
AB  - The centrosome is a major microtubule-organizing center in animal cells, and its
      intracellular positioning is critical for defining intracellular architecture.
      The centrosome positions itself at the cell center. Centrosome centration depends
      on the microtubule cytoskeleton. To accomplish robust centration regardless of
      the cell size or cell shape, it has been assumed that the force mediated by the
      microtubules depends on microtubule length. However, a concrete mechanism to
      generate forces to pull the centrosome in a microtubule length-dependent manner
      has been elusive. Recently, we successfully demonstrated that centrosome-directed
      movement of intracellular organelles along microtubules drives centrosome
      centration in the Caenorhabditis elegans early embryo. Based on this observation,
      we proposed the centrosome-organelle mutual pulling model in which the reaction
      forces of organelle transport generated along microtubules act as a driving force
      that pulls the centrosomes toward the cell center. This is the first experiment
      based model that accounts for the microtubule length-dependent pulling force
      generated in the cytoplasm contributing to centrosome centration. Intriguingly,
      this model is consistent with a recent estimation that the pulling force is
      proportional to the cubic length of microtubules.

PMID- 21866268
TI  - Regulation of localization and activity of the microtubule depolymerase MCAK.
AB  - Mitotic Centromere Associated Kinesin (MCAK) is a potent microtubule
      depolymerizing and catastrophe-inducing factor, which uses the energy of ATP
      hydrolysis to destabilize microtubule ends. MCAK is localized to inner
      centromeres, kinetochores and spindle poles of mitotic cells, and is also present
      in the cytoplasm. Both in interphase and in mitosis, MCAK can specifically
      accumulate at the growing microtubule ends. Here we discuss the mechanisms, which
      modulate subcellular localization and activity of MCAK through the interaction
      with the End Binding (EB) proteins and phosphorylation.

PMID- 21866269
TI  - Formin mDia3: A novel target for Aurora B kinase.
AB  - Stable attachment of kinetochores to spindle microtubules is essential for
      accurate chromosome segregation. We have shown that a kinetochore-associated
      formin protein, mDia3, contributes to the generation of stable kinetochore
      microtubule attachment. The published report reviewed here shows an essential
      role of mDia3 in achieving metaphase chromosome alignment, and this function is
      directly regulated by Aurora B phosphorylation. Aurora B is a central component
      during the capture of spindle microtubules by kinetochores, in which it
      selectively eliminates incorrect attachments by phosphorylating a group of
      microtubule binding proteins at kinetochores to reduce their microtubule binding
      affinity. Here, we discuss the roles of Aurora B kinase and its substrates in
      achieving proper kinetochore-microtubule attachment.

PMID- 21866270
TI  - Looking for the functions of RNA granules in ALK-transformed cells.
AB  - Numerous cytoplasmic foci containing mRNA s and their associated proteins have
      been described in mammalian somatic and germ cells. The best studied examples are
      given by the processing bodies (PBs) that are present in all cell types, and the
      stress granules (SGs) that are transiently formed following stress stimuli. Those
      foci are non-membranous dynamic structures that, through the continuous exchange
      of their content with the cytoplasm, are believed to control mRNA storage,
      translation and degradation. However, due in part to the fact that their
      composition has not been fully characterized, their relevance to mRNA regulation
      and cell survival remains a matter of debate. In a recent study, we described new
      cytoplasmic foci that form specifically in transformed cells expressing the
      constitutively active ALK tyrosine kinase. Those granules, further called AGs for
      ALK granules, contain polyadenylated mRNAs but are distinct from PBs and SGs.
      Using a method based on sucrose density gradient fractionation, we further
      purified AGs and identified their mRNA content. We discuss our findings in
      relation to other granules containing untranslated mRNAs and speculate on the
      possible contribution of AGs to the oncogenic properties of ALK-expressing cells.

PMID- 21866271
TI  - Detection of a troponin I-like protein in non-striated muscle of the tardigrades
      (water bears).
AB  - Tardigrades, also known as water bears, have somatic muscle fibers that are
      responsible for movement of their body and legs. These muscle fibers contain thin
      and thick filaments in a non-striated pattern. However, the regulatory mechanism
      of muscle contraction in tardigrades is unknown. In the absence of extensive
      molecular and genomic information, we detected a protein of 31 kDa in whole
      lysates of tardigrades that cross-reacted with the antibody raised against
      nematode troponin I (TnI). TnI is a component of the troponin complex that
      regulates actin-myosin interaction in a Ca(2+)-dependent and actin-linked manner.
      This TnI-like protein was co-extracted with actin in a buffer containing ATP and
      EGTA, which is known to induce relaxation of a troponin-regulated contractile
      system. The TnI-like protein was specifically expressed in the somatic muscle
      fibers in adult animals and partially co-localized with actin filaments in a non
      striated manner. Interestingly, the pharyngeal muscle did not express this
      protein. These observations suggest that the non-striated somatic muscle of
      tardigrades has an actin-linked and troponin-regulated system for muscle
      contraction.

PMID- 21866272
TI  - TRIM5 acts as more than a retroviral restriction factor.
AB  - The retrovirus restriction factor TRIM5alpha blocks post-entry infection of
      retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase,
      TRIM5alpha binds to the retroviral capsid lattice in the cytoplasm of an infected
      cell and accelerates the uncoating process of retroviral capsid, thus providing a
      potent restriction to HIV-1 and other retrovirus infections. The precise
      mechanism by which this restriction is imposed remains under scrutiny, and
      evidence is lacking to link the E3 ubiquitin ligase activity of TRIM5alpha to its
      ability to restrict retrovirus infection. In a recent study, Pertel and
      colleagues have uncovered the link between the two, providing compelling evidence
      to suggest that following the interaction with the retroviral capsid, TRIM5
      triggers an antiviral innate immune response by functioning as a pattern
      recognition receptor. This unique function of TRIM5 is dependent on its
      association with the E2 ubiquitin-conjugating enzyme complex UBC13-UEV1A and
      subsequent activation of the TAK1 kinase complex and downstream genes involved in
      innate immune responses. These findings have defined a novel function for TRIM5
      as a pattern recognition receptor in innate immune recognition and provided
      valuable mechanistic insight into its role as a retroviral restriction factor.
      Here we discuss the significance of these new findings in understanding TRIM5
      mediated HIV restriction.

PMID- 21866273
TI  - Environmental toxicants and male reproductive function.
AB  - Environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine
      disruptors. In utero, perinatal or neonatal exposure of BPA to rats affect the
      male reproductive function, such as the blood-testis barrier (BTB) integrity.
      This effect of BPA on BTB integrity in immature rats is likely mediated via a
      loss of gap junction function at the BTB, failing to coordinate tight junction
      and anchoring junction function at the site to maintain the immunological barrier
      integrity. This in turn activates the extracellular signal-regulated kinases 1/2
      (Erk1/2) downstream and an increase in protein endocytosis, destabilizing the
      BTB. The cadmium-induced disruption of testicular dysfunction is mediated
      initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK)
      complex at the BTB, causing redistribution of proteins at the Sertoli-Sertoli
      cell interface, leading to the BTB disruption. The damaging effects of these
      toxicants to testicular function are mediated by mitogen-activated protein
      kinases (MAPK) downstream, which in turn perturbs the actin bundling and
      accelerates the actin-branching activity, causing disruption of the Sertoli cell
      tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion
      at the apical ectoplasmic specialization (apical ES, a testis-specific anchoring
      junction type) that leads to premature release of germ cells from the testis.
      However, the use of specific inhibitors against MAPK was shown to block or delay
      the cadmium-induced testicular injury, such as BTB disruption and germ cell loss.
      These findings suggest that there may be a common downstream p38 and/or Erk1/2
      MAPK-based signaling pathway involving polarity proteins and actin regulators
      that is shared between different toxicants that induce male reproductive
      dysfunction. As such, the use of inhibitors and/or antagonists against specific
      MAPKs can possibly be used to "manage" the illnesses caused by these toxicants
      and/or "protect" industrial workers being exposed to high levels of these
      toxicants in their work environment.

PMID- 21866275
TI  - Desmosomes in the testis: Moving into an unchartered territory.
AB  - Desmosomes are cell-cell junctions that link to cytoplasmic intermediate
      filaments, and they are known to mediate robust and stable adhesion in organs
      such as the skin and heart. Desmosomes are also present between apposing Sertoli
      cells at the blood-testis barrier, and between Sertoli cells and all germ cells
      up to, but not including, step 8 spermatids in the seminiferous epithelium.
      Unfortunately, they remain to be one of the least studied cell junction types in
      the seminiferous epithelium of the mammalian testis. In this article, we briefly
      discuss how kinases and the actin cytoskeleton relate to the study of desmosomes
      in the testis. It is hoped that this information is used to initiate more studies
      on the biology of the desmosome in the future.

PMID- 21866276
TI  - Failure of acrosome formation and globozoospermia in the wobbler mouse, a Vps54
      spontaneous recessive mutant.
AB  - The acrosome is a unique organelle that plays an important role at fertilization
      and during sperm morphogenesis and that is absent in globozoospermia, an
      inherited infertility syndrome in humans. At the light of recent experimental
      evidence, the acrosome is considered a lysosome-related organelle to whose
      biogenesis both the endocytic and biosynthetic pathways contribute. Vps54 is a
      vesicular sorting protein involved in the retrograde traffic; the recessive
      Vps54(L967Q) mutation in the mouse results in the wobbler phenotype,
      characterized by motor-neuron degeneration and male infertility. Here we have
      investigated the spatio-temporal occurrence/progression of the wobbler fertility
      disorder starting from mice at post-natal day 35, the day of the first event of
      spermiation. We show that the pathogenesis of wobbler infertility originates at
      the first spermiogenetic wave, affecting acrosome formation and sperm head
      elongation. Vps54(L967Q)-labeled vesicles, on the contrary of the wild-type Vps54
      labeled ones, are not able to coalesce into a larger vesicle that develops,
      flattens and shapes to give rise to the acrosome. Evidence that it is the
      malfunctioning of the endocytic traffic to hamper the development of the acrosome
      comes out from the study on UBPy. UBPy, a deubiquitinating enzyme, is a marker of
      acrosome biogenesis from the endocytic pathway. In wobbler spermatids UBPy
      positive endosomes remain single, scattered vesicles that do not contribute to
      acrosome formation. As secondary defect of wobbler spermiogenesis, spermatid
      mitochondria are misorted; moreover, with the progression of the age/disease also
      Sertoli-germ cell adhesions are compromised suggesting a derailment in the
      endocytic route that underlies their restructuring.

PMID- 21866274
TI  - Spermiation: The process of sperm release.
AB  - Spermiation is the process by which mature spermatids are released from Sertoli
      cells into the seminiferous tubule lumen prior to their passage to the
      epididymis. It takes place over several days at the apical edge of the
      seminiferous epithelium, and involves several discrete steps including
      remodelling of the spermatid head and cytoplasm, removal of specialized adhesion
      structures and the final disengagement of the spermatid from the Sertoli cell.
      Spermiation is accomplished by the co-ordinated interactions of various
      structures, cellular processes and adhesion complexes which make up the
      "spermiation machinery". This review addresses the morphological, ultrastructural
      and functional aspects of mammalian spermiation. The molecular composition of the
      spermiation machinery, its dynamic changes and regulatory factors are examined.
      The causes of spermiation failure and their impact on sperm morphology and
      function are assessed in an effort to understand how this process may contribute
      to sperm count suppression during contraception and to phenotypes of male
      infertility.

PMID- 21866277
TI  - TGFbeta superfamily signaling regulators are differentially expressed in the
      developing and adult mouse testis.
AB  - Transforming growth factor-beta (TGFbeta) superfamily ligands are produced by and
      act upon testicular cells to control testis morphogenesis and adult fertility.
      Ligand production changes during testis development and dysregulated signaling
      affects the number of cells comprising each lineage and their development, with
      several components of this diverse signaling pathway linked to male infertility.
      To test the hypothesis that TGFbeta superfamily signaling regulators are
      differentially expressed during mouse testis development, we surveyed expression
      of Hgs, Zfyve9, Smurf1 and Net25 by northern blot and in situ hybridization and
      SMURF2 and MAN1 by western blot and immunohistochemistry. Expression of these
      genes is highly regulated and differs between the first spermatogenic wave and
      adult spermatogenesis. Zfyve9 transcripts were first detected in Sertoli cells
      and spermatogonia at 5 days post partum (dpp) whereas Hgs mRNA was first detected
      in pachytene spermatocytes at 15 dpp. Smurf1 mRNA was broadly expressed at 0 and
      5 dpp but restricted to spermatogonia and early spermatocytes at 15 dpp and
      spermatogonia, spermatocytes and round spermatids in adults. SMURF2 was limited
      to gonocyte nuclei at birth but was nuclear in all cells at 5 dpp. SMURF2 was
      absent from 15 dpp differentiating spermatogonia and early spermatocytes but
      readily detected in adult pachytene spermatocytes and round spermatids. MAN1 and
      Net25 also had different expression profiles, with MAN1 undetectable at 5 dpp.
      Differential synthesis of signaling modulators explains how Sertoli cells and
      spermatogenic cells, which all possess TGFbeta superfamily signaling machinery
      and reside within the same microenvironment, respond differently to the same
      ligand.

PMID- 21866279
TI  - Factors associated with utilization of HAART amongst hard-to-reach HIV-infected
      individuals in Atlanta, Georgia.
AB  - The study is aimed at identifying clinical, demographic and behavioral factors,
      including participation in HIV care, associated with the utilization of
      antiretroviral therapy (ART), among hard-to-reach HIV-positive individuals in
      Atlanta, GA. The study included 184 HIV-positive participants of the Infectious
      Disease Program (IDP) of the Grady Health System between February 1999 to March
      2001. Individuals were categorized as regular attendees (those who consistently
      kept their outpatient appointments, n = 65), irregular (those who inconsistently
      kept their appointments, n = 60) or non-attendees (those who failed routinely to
      keep their appointments, n = 59). Univariate and multivariate analyses using log
      binomial regression modeling were done. HIV-infected individuals who consistently
      kept their appointments at the IDP received ART at a frequency (86%) that is
      twice that of those who missed some appointments (42%) and four times that of
      those who routinely failed to keep appointments (20%). In multivariate analysis,
      category of clinic attendance (regular, irregular or non-attendee) was the only
      risk factor independently associated with utilization of ART: Regular attendees
      (RR = 3.59, 95% CI 2.12 to 6.08) and irregular attendees (RR = 2.26, 95% CI 1.28
      to 4.01) compared to non-attendees. The positive association between routine
      clinic attendance and use of antiretroviral therapy observed in this study should
      encourage the development of strategies to retain patients in outpatient HIV
      care.

PMID- 21866278
TI  - The beta1-integrin-p-FAK-p130Cas-DOCK180-RhoA-vinculin is a novel regulatory
      protein complex at the apical ectoplasmic specialization in adult rat testes.
AB  - During spermatogenesis, step 1 spermatids (round spermatids) derive from
      spermatocytes following meiosis I and II at stage XIV of the epithelial cycle
      begin a series of morphological transformation and differentiation via 19 steps
      in rats to form spermatozoa. This process is known as spermiogenesis, which is
      marked by condensation of the genetic material in the spermatid head, formation
      of the acrosome and elongation of the tail. Since developing spermatids are
      lacking the robust protein synthesis and transcriptional activity, the cellular,
      molecular and morphological changes associated with spermiogenesis rely on the
      Sertoli cell in the seminiferous epithelium via desmosome and gap junction
      between Sertoli cells and step 1-7 spermatids. Interestingly, a unique anchoring
      junction type arises at the interface of step 8 spermatid and Sertoli cell known
      as apical ectoplasmic specialization (apical ES). Once it appears, apical ES is
      the only anchoring device restricted to the interface of step 8-19 spermatids and
      Sertoli cells to confer spermatid polarity, adhesion, signal communication and
      structural support, and to provide nutritional support during spermiogenesis,
      replacing desmosome and gap junction. While the adhesion protein complexes that
      constitute the apical ES are known, the signaling protein complexes that regulate
      apical ES dynamics, however, remain largely unknown. Herein we report the
      presence of a FAK (focal adhesion kinase)-p130Cas (p130 Crk-associated substrate)
      DOCK180 (Dedicator of cytokinesis 180)-RhoA (Ras homolog gene family, member A)
      vinculin signaling protein complex at the apical ES, which is also an integrated
      component of the beta1-integrin-based adhesion protein complex based on co
      immunoprecipitation experiment. It was also shown that besides p-FAK-Tyr(397) and
      p-FAK-Tyr(576), beta1-integrin, p130Cas, RhoA and vinculin displayed stage
      specific expression in the seminiferous epithelium during the epithelial cycle
      with predominant localization at the apical ES as demonstrated by
      immunohistochemistry. Based on these findings, functional studies can now be
      performed to assess the role of this beta1-integrin-p-FAK-p130Cas-DOCK180-RhoA
      vinculin protein complex in apical ES dynamics during spermiogenesis.

PMID- 21866280
TI  - A survey on the management of acute rhinosinusitis among Asian physicians.
AB  - BACKGROUND: Based on the 'European Position Paper on Rhinosinusitis and Nasal
      polyps (EP3OS 2007)', this study aimed to investigate general practitioners (GPs)
      and other specialists' understanding when managing patients with acute
      rhinosinusitis (ARS) in Asia. METHODOLOGY: Among a total of 2662 questionnaires
      completed, 2524 (94.8%) were valid for analysis. There were 1308 GPs (51.8%), 989
      otolaryngologists (39.2%) and 227 paediatricians (9%) from Mainland China, Hong
      Kong, Indonesia, India, Malaysia, Pakistan, Philippines, Singapore, Thailand and
      Taiwan. RESULTS: ARS is affecting an estimated 6 - 10% of patients seen in a
      daily out-patient practice. The EP3OS criteria are well supported by Asian
      physicians (94.1%). Most physicians (62.7%) agreed that radiological
      investigation is not needed to diagnose ARS. However, even for mild ARS (common
      cold), medical treatments were still recommended by 87% of GPs, 83.9% of
      otolaryngologists, and 70% of paediatricians. The top three first-line treatments
      prescribed were antihistamines (39.2%), nasal decongestants (33.6%), and
      antibiotics (29.5%). Antibiotics usage increased as the first line treatment of
      moderate (45.9%) and severe (60.3%) ARS. CONCLUSION: ARS is commonly managed by
      GPs, otolaryngologists, and paediatricians in Asia. However, understanding of the
      management of ARS needs further improvement to minimize unnecessary use of
      radiological investigations, overuse of antibiotics, and under use of nasal
      corticosteroids.

PMID- 21866281
TI  - Intra- and inter-monomeric transfers in the light harvesting LHCII complex: the
      Redfield-Forster picture.
AB  - We further develop the model of energy transfer in the LHCII trimer based on a
      quantitative fit of the linear spectra (including absorption (OD), linear
      dichroism (LD), circular dichroism (CD), and fluorescence (FL)) and transient
      absorption (TA) kinetics upon 650 nm and 662 nm excitation. The spectral shapes
      and relaxation/migration rates have been calculated using the combined Redfield
      Forster approach capable of correctly describing fast relaxation within strongly
      coupled chlorophyll (Chl) a and b clusters and slow migration between them.
      Within each monomeric subunit of the trimeric complex there is fast (sub-ps)
      conversion from Chl's b to Chl's a at the stromal side accompanied by slow (>10
      ps) equilibration between the stromal- and lumenal-side Chl a clusters in
      combination with slow (>13 ps) population of Chl's a from the 'bottleneck' Chl
      a604 site. The connection between monomeric subunits is determined by exciton
      coupling between the stromal-side Chl's b from the two adjacent subunits (Chl
      b601'-608-609 cluster) making a simultaneous fast (sub-ps) population of the
      Chl's a possible from both subunits. Final equilibration occurs via slow (>20 ps)
      migration between the Chl a clusters located on different monomeric subunits.
      This migration includes up-hill transfers from the red-most Chl a610-611-612
      clusters located at the peripheral side in each subunit to the Chl a602-603
      dimers located at the inner side of the trimeric LHCII complex.

PMID- 21866282
TI  - Indium sulfide clusters integrated with 2,2'-bipyridine complexes.
AB  - Supertetrahedral compounds of chalcogenometalates (T3 cluster compounds)
      integrated with Ni-bpy (bpy = 2,2'-bipyridine) complex were prepared by a
      solvothermal technique. The compound
      [Ni(bpy)(3)](3)[H(4)In(10)S(20)].bpy.2EG.6H(2)O (Mb-InS-1) (EG = ethylene glycol)
      consists of discrete T3 clusters of [H(4)In(10)S(20)](6-) with three
      [Ni(bpy)(3)](2+) cations. The compound
      [Ni(bpy)(3)](2)[H(2)In(10)S(19)].bpy.2HEA.2H(2)O (Mb-InS-2) (EA = ethanolamine)
      is a 1-D polymer, in which zigzag T3 cluster chains are charge balanced by metal
      bpy complex cations. The compound
      [Ni(bpy)(3)](7)[H(4)In(40)S(74)].7Hbpy.3HEA.8H(2)O (Mb-InS-3) is a 2-D T3 polymer
      with cation layers of [Ni(bpy)(3)](2+). Integrating M-bpy complex cations into
      chalcogenido structures has been made with the aim of improving the
      photoabsorption of the materials. The electronic spectra showed the new bands of
      cation-anion charge-transfer (CACT) that is mainly caused by the S...H-C(py)
      contacts between the InS T3 supertetrahedral clusters and the [Ni(bpy)(3)](2+)
      cations.

PMID- 21866283
TI  - Switching on oxygen activation by cobalt complexes of pentadentate ligands.
AB  - The monoanionic N(4)O ligand N-methyl-N,N'-bis(2-pyridylmethyl)ethylenediamine-N'
      acetate (mebpena(-)) undergoes oxidative C-N bond cleavage in the presence of
      Co(II) and O(2). The two resultant fragments are coordinated to the metal ion in
      the product [Co(III)(2-pyridylformate)(mepena)]ClO(4) (mepena(-) = N-methyl-N'-(2
      pyridylmethyl)ethylenediamine-N'-acetato). Bond cleavage does not occur in the
      presence of chloride ions and [Co(III)(mebpena)Cl](+), containing intact mebpena(
      ), can be isolated. The oxidative instability of the mebpena(-) in the presence
      of Co(II) and air stands in contrast to the oxidative stability of the family of
      very closely related penta- and hexa-dentate ligands in their cobalt complexes.
      Cyclic voltammetry on the matched pair [Co(III)Cl(mebpena)](+) and
      [Co(II)Cl(bztpen)](+), bztpen = N-benzyl-N,N',N'-tris(2
      pyridylmethyl)ethylenediamine, shows that substitution of a pyridine donor for a
      carboxylato donor results in a relatively small cathodic shift of 150 mV in the E
      degrees (Co(II)/Co(III)) oxidation potential, presumably this is enough to
      determine the contrasting metal oxidation state in the complexes isolated under
      ambient conditions. DFT calculations support a proposal that [Co(II)(mebpena)](+)
      reacts with O(2) to form a Co(III)-superoxide complex which can abstract an H
      atom from a ligand methylene C atom as the initial step towards the observed
      oxidative C-N bond cleavage.

PMID- 21866284
TI  - Nickel(II) and iron(II) triple helicates assembled from expanded quaterpyridines
      incorporating flexible linkages.
AB  - In the present study the interaction of Fe(II) and Ni(II) with the related
      expanded quaterpyridines, 1,2-, 1,3- and 1,4-bis-(5'-methyl-[2,2']bipyridinyl-5
      ylmethoxy)benzene ligands (4-6 respectively), incorporating flexible, bis
      aryl/methylene ether linkages in the bridges between the dipyridyl domains, was
      shown to predominantly result in the assembly of [M(2)L(3)](4+) complexes;
      although with 4 and 6 there was also evidence for the (minor) formation of the
      corresponding [M(4)L(6)](8+) species. Overall, this result contrasts with the
      behaviour of the essentially rigid 'parent' quaterpyridine 1 for which only
      tetrahedral [M(4)L(6)](8+) cage species were observed when reacted with various
      Fe(II) salts. It also contrasts with that observed for 2 and 3 incorporating
      essentially rigid substituted phenylene and biphenylene bridges between the
      dipyridyl domains where reaction with Fe(II) and Ni(II) yielded both
      [M(2)L(3)](4+) and [M(4)L(6)](8+) complex types, but in this case it was the
      latter species that was assigned as the thermodynamically favoured product type.
      The X-ray structures of the triple helicate complexes
      [H(2)O?Ni(2)(4)(3)](PF(6))(4).THF.2.2H(2)O,
      [Ni(2)(6)(3)](PF(6))(4).1.95MeCN.1.2THF.1.8H(2)O, and the very unusual triple
      helicate PF(6)(-) inclusion complex,
      [(PF(6))?Ni(2)(5)(3)](PF(6))(3).1.75MeCN.5.25THF.0.25H(2)O are reported.

PMID- 21866285
TI  - Interfacial behavior of immortalized hypothalamic mouse neurons detected by
      acoustic wave propagation.
AB  - The attachment of immortalized hypothalamic murine neurons onto the surface of an
      acoustic wave device yields both positive series resonant frequency (f(s)) and
      motional resistance (R(m)) shifts as opposed to commonly reported negative f(s)
      and positive R(m) shifts observed for other cell types. These unique shifts have
      been confirmed by a variety of experiments in order to verify the source and the
      validity of the signals. These studies involved monitoring responses to solution
      flow, the absence of serum proteins, the effect of reducing specific cell 
      surface interactions and the disruption of the neuronal cytoskeleton components.
      For the adhesion and deposition of neurons, f(s) and R(m) shifts are positively
      correlated to the amount of adhered neurons on the sensor surface, whereas non
      adhered neurons do not produce any significant change in the monitored
      parameters. In the absence of serum proteins, initial cell adhesion is followed
      by subsequent cell death and removal from the sensor surface. The presence of the
      peptide, GRGDS is observed to significantly reduce cell-surface specific
      interactions compared to the control of SDGRG and this produces f(s) and R(m)
      responses that are opposite in direction to that observable for cell adhesion.
      Cytoskeletal studies, using the drugs nocodazole (10 MUM), colchicine (1 MUM),
      cytochalasin B (10 MUM) and cytochalasin D (2 MUM) all elicit neuronal responses
      that are validated by phalloidin actin-filament staining. These results indicate
      that the responses are associated with a wide range of cellular changes that can
      be monitored and studied using the acoustic wave method in real time, under
      optimal physiological conditions.

PMID- 21866295
TI  - Interaction of glycated human serum albumin with endothelial cells in a
      hemodynamic environment: structural and functional correlates.
AB  - Advanced glycation end products (AGEs) are known to be involved in the
      pathogenesis of several diseases, in particular diabetes, via signaling through
      their receptor. Numerous studies have been carried out on protein-sugar
      interactions at very high concentrations of the latter. The objective of this
      investigation was to determine the effects of nonenzymatic glycation induced by
      reducing sugars on the secondary structure of human serum albumin (HSA) under
      different physiological conditions and to correlate that with expression of RAGE
      (receptor for advanced glycation end products) on HUVECs (human umbilical vein
      endothelial cells) in a controlled hemodynamic environment. Our results indicate
      that RAGE expression is shear stress modulated and that glycated HSA enhances the
      expression further. The secondary structure of AGE-HSA derived from glucose at 20
      mM contains higher alpha-helical content and elicits maximum expression of the
      receptor. The effect of shear stress at 10 dynes cm(-2) is independent of AGE
      HSA.

PMID- 21866296
TI  - Intrinsically disordered regions have specific functions in mitochondrial and
      nuclear proteins.
AB  - Proteins in general consist not only of globular structural domains (SDs), but
      also of intrinsically disordered regions (IDRs), i.e. those that do not assume
      unique three-dimensional structures by themselves. Although IDRs are especially
      prevalent in eukaryotic proteins, the functions are mostly unknown. To elucidate
      the functions of IDRs, we first divided eukaryotic proteins into subcellular
      localizations, identified IDRs by the DICHOT system that accurately divides
      entire proteins into SDs and IDRs, and examined charge and hydropathy
      characteristics. On average, mitochondrial proteins have IDRs more positively
      charged than SDs. Comparison of mitochondrial proteins with orthologous
      prokaryotic proteins showed that mitochondrial proteins tend to have segments
      attached at both N and C termini, high fractions of which are IDRs. Segments
      added to the N-terminus of mitochondrial proteins contain not only signal
      sequences but also mature proteins and exhibit a positive charge gradient, with
      the magnitude increasing toward the N-terminus. This finding is consistent with
      the notion that positively charged residues are added to the N-terminus of
      proteobacterial proteins so that the extended proteins can be chromosomally
      encoded and efficiently transported to mitochondria after translation. By
      contrast, nuclear proteins generally have positively charged SDs and negatively
      charged IDRs. Among nuclear proteins, DNA-binding proteins have enhanced charge
      tendencies. We propose that SDs in nuclear proteins tend to be positively charged
      because of the need to bind to negatively charged nucleotides, while IDRs tend to
      be negatively charged to interact with other proteins or other regions of the
      same proteins to avoid premature proteasomal degradation.

PMID- 21866298
TI  - Increased levels of platelet activation markers are positively associated with
      carotid wall thickness and other atherosclerotic risk factors in obese patients.
AB  - The role of platelets in the development of atherosclerosis and obesity-related
      prothrombotic state is still under investigation. In this cross-sectional cohort
      study, we measured the levels of different platelet activation markers and
      evaluated their relationship with carotid intima-media thickness (IMT) along with
      other atherosclerotic risk factors in obese patients with or without
      atherosclerotic co-morbidities. We enrolled 154 obese patients, including 98 with
      either hypertension, type 2 diabetes mellitus or dyslipidaemia, 56 without these
      co-morbidities and 62 age- and sex-matched healthy controls. Platelet P-selectin
      expression and the number of platelet-derived microparticles (PMPs) were measured
      by flow cytometry; soluble P-selectin levels were analysed by ELISA and Thr715Pro
      P-selectin polymorphism was determined by PCR-RFLP. Carotid IMT was examined by
      ultrasonography. The levels of platelet activation parameters were significantly
      elevated in all obese subjects with increased carotid IMT compared to healthy
      controls. There was no effect of Thr715Pro genotype on soluble P-selectin levels
      in obese individuals contrary to normal subjects. Significant and positive
      association was revealed between carotid IMT and platelet P-selectin (p<0.0001),
      soluble P-selectin (p=0.039) and PMP (p=0.0001) levels. After adjusting for
      multiple variables, independent association was found between soluble P-selectin
      and fibrinogen (p=0.007), PMP levels and body mass index (p<0.0001) as well as
      platelet P-selectin and carotid IMT (p=0.012) plus plasminogen activator
      inhibitor-1 (p=0.009). In conclusion, P-selectin and PMP levels showed positive
      associations with abnormal carotid IMT and other risk factors in obesity
      suggesting a critical role of enhanced platelet reactivity in atherosclerotic
      wall alteration.

PMID- 21866297
TI  - Formulating a fluorogenic assay to evaluate S-adenosyl-L-methionine analogues as
      protein methyltransferase cofactors.
AB  - Protein methyltransferases (PMTs) catalyze arginine and lysine methylation of
      diverse histone and nonhistone targets. These posttranslational modifications
      play essential roles in regulating multiple cellular events in an epigenetic
      manner. In the recent process of defining PMT targets, S-adenosyl-L-methionine
      (SAM) analogues have emerged as powerful small molecule probes to label and
      profile PMT targets. To examine efficiently the reactivity of PMTs and their
      variants on SAM analogues, we transformed a fluorogenic PMT assay into a ready
      high throughput screening (HTS) format. The reformulated fluorogenic assay is
      featured by its uncoupled but more robust character with the first step of
      accumulation of the commonly-shared reaction byproduct S-adenosyl-L-homocysteine
      (SAH), followed by SAH-hydrolase-mediated fluorogenic quantification. The HTS
      readiness and robustness of the assay were demonstrated by its excellent Z'
      values of 0.83-0.95 for the so-far-examined 8 human PMTs with SAM as a cofactor
      (PRMT1, PRMT3, CARM1, SUV39H2, SET7/9, SET8, G9a and GLP1). The fluorogenic assay
      was further implemented to screen the PMTs against five SAM analogues (allyl-SAM,
      propargyl-SAM, (E)-pent-2-en-4-ynyl-SAM (EnYn-SAM), (E)-hex-2-en-5-ynyl-SAM (Hey
      SAM) and 4-propargyloxy-but-2-enyl-SAM (Pob-SAM)). Among the examined 8 * 5 pairs
      of PMTs and SAM analogues, native SUV39H2, G9a and GLP1 showed promiscuous
      activity on allyl-SAM. In contrast, the bulky SAM analogues, such as EnYn-SAM,
      Hey-SAM and Pob-SAM, are inert toward the panel of human PMTs. These findings
      therefore provide the useful structure-activity guidance to further evolve PMTs
      and SAM analogues for substrate labeling. The current assay format is ready to
      screen methyltransferase variants on structurally-diverse SAM analogues.

PMID- 21866299
TI  - Neutrophils and clinical outcomes in patients with acute coronary syndromes
      and/or cardiac revascularisation. A systematic review on more than 34,000
      subjects.
AB  - Some studies have suggested that high levels of total white blood cell (WBC)
      count and C-reactive protein (CRP) may be considered as independent prognostic
      factors in patients with acute coronary syndromes (ACS) and/or after cardiac
      revascularisation by percutaneous coronary intervention or coronary artery bypass
      grafting surgery. Evidence on the role of neutrophils in cardiovascular disease
      is less compelling. Therefore, we conducted a systematic review of the literature
      with the aim of identifying all the available evidence to clarify the role of
      neutrophils (absolute or relative count, neutrophil/lymphocyte ratio) as a
      prognostic risk factor in patients with ACS and/or cardiac revascularisation. All
      published studies evaluating the role of neutrophils as a risk factor for
      clinical outcomes were assessed using the MEDLINE and EMBASE databases. Study
      selection, data extraction and validity assessment was performed independently by
      two reviewers. Twenty-one studies (17 of which had positive results) for a total
      of more than 34,000 patients were included. Ten of 13 studies in ACS patients
      found that neutrophils measured on-admission are related to mortality rate and/or
      to major adverse clinical events. A predictive value of neutrophils after cardiac
      revascularisation procedures was reported in seven out of eight studies. Most of
      the studies showed that neutrophils were independent predictors of cardiovascular
      outcomes when analysed concomitantly with other markers of inflammation (WBC,
      CRP). The findings of our systematic review highlight the potential application
      of this inexpensive and readily available inflammatory marker for risk
      stratification in patients with ACS and/or cardiac revascularisation.

PMID- 21866300
TI  - Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen.
AB  - Tamoxifen is a known anti-cancer drug and established estrogen receptor
      modulator. Few clinical studies have earlier implicated the drug in thrombotic
      complications attributable to lower anti-thrombin and protein S levels in plasma.
      However, action of tamoxifen on platelet signalling machinery has not been
      elucidated in detail. In the present report we show that tamoxifen is endowed
      with significant inhibitory property against human platelet aggregation. From a
      series of in vivo and in vitro studies tamoxifen was found to inhibit almost all
      platelet functions, prolong tail bleeding time in mouse and profoundly prevent
      thrombus formation at injured arterial wall in mice, as well as on collagen
      matrix perfused with platelet-rich plasma under arterial shear against the
      vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen
      significantly downregulates platelet responses and holds potential as a promising
      anti-platelet/anti-thrombotic agent.

PMID- 21866302
TI  - Mast cells in atherosclerosis.
AB  - The mast cell, a potent inflammatory cell type, is widely distributed over
      several tissues, but particularly prominent at the interface exposed to the
      environment to act in the first line of defense against pathogens. Upon
      activation mast cells release granules, which contain a large panel of mediators,
      including neutral proteases (e.g. chymase and tryptase), cathepsins, heparin,
      histamine and a variety of cytokines and growth factors. While mast cells have
      been demonstrated to be critically involved in a number of Th2 dominated diseases
      such as asthma and allergy, recent investigations have now also implicated mast
      cells in the pathogenesis of atherosclerosis and acute cardiovascular syndromes.
      In this review, we will discuss the contribution of mast cells to the initiation
      and progression of atherosclerosis and gauge the therapeutic opportunities of
      mast cell targeted intervention in acute cardiovascular syndromes.

PMID- 21866301
TI  - Hypercoagulability biomarkers in Trypanosoma cruzi -infected patients.
AB  - There is a current controversy over the hypothesis that a number of
      thromboembolic events could be related to hypercoagulable state in patients with
      chronic Chagas disease. This study was designed to determine whether a
      prothrombotic state existed in chronic Trypanosoma cruzi-infected patients and,
      if so, to describe its evolution after treatment with Benznidazole. Twenty-five
      patients with chronic Chagas disease and 18 controls were evaluated. The markers
      used were prothrombin time, activated partial thromboplastin time, fibrinogen,
      antithrombin, plasminogen, protein C, total protein S, free protein S, factor
      VIII, D-dimer, activated factor VIIa, tissue-type plasminogen activator inhibitor
      1, prothrombin fragment 1+2 (F1+2), plasmin-antiplasmin complexes, soluble P
      selectin and endogenous thrombin potential (ETP). Despite statistically
      significant differences between cases and controls in several markers, only ETP
      (which quantifies the ability of plasma to generate thrombin when activated
      through tissue factor addition) (p<0.0001) and F1+2 (a marker of thrombin
      generation in vivo) (p<0.0001) showed values outside the normal levels in
      patients compared with controls. Similar results were obtained in these markers
      six months after treatment in the cohort of cases (p<0.0008 and p<0.004,
      respectively). These results may be relevant in clinical practice. Though current
      treatment for Chagas disease is still controversial, if it were considered as a
      thromboembolic risk factor the antiparasitic treatment strategy could be
      reinforced. The results also support further research on haemostasis parameters
      as candidates for early surrogate biomarkers of cure or progression of Chagas
      disease.

PMID- 21866303
TI  - Transient atrial fibrillation and risk of stroke after acute myocardial
      infarction.
AB  - Atrial fibrillation (AF) is a frequent complication of acute myocardial
      infarction (AMI). In the AMI setting, AF is frequently brief and attributed to
      acute haemodynamic changes, inflammation or ischaemia. However, it remains
      uncertain whether transient AF episodes are associated with a subsequent
      increased risk of ischaemic stroke. We studied the impact of transient new-onset
      AF on the one-year risk of ischaemic stroke or transient ischaemic attack (TIA)
      in a retrospective cohort of 2,402 patients with AMI. Patients with previous AF
      or AF at hospital discharge were excluded. Transient AF occurred in 174 patients
      (7.2%) during the initial hospitalisation. During one year follow-up after
      hospital discharge, stroke or TIA occurred in 16 (9.2%) and 58 (2.6%) patients
      with and without transient AF, respectively (p< 0.0001). Compared with patients
      without transient AF, the adjusted hazard ratio for stroke or TIA in patients
      with transient AF was 3.03 (95% CI 1.73-5.32; p< 0.0001). Stroke or TIA occurred
      in 2.6% of patients without AF, 6.3% of patients with transient AF treated with
      oral anticoagulants, and 9.9% of patients with transient AF treated with
      antiplatelet agents. The incidence of recurrent AF after hospital discharge was
      markedly higher in patients with transient AF during the index hospitalisation
      (22.8% vs. 2.0%, p< 0.0001). In conclusion, transient AF complicating AMI is
      associated with an increased future risk of ischaemic stroke and TIA,
      particularly in patients treated with antiplatelet agents alone. High AF
      recurrence rates in these patients also suggest that oral anticoagulants should
      be strongly considered.

PMID- 21866304
TI  - Inhibitory effects of lactoferrin on biofilm formation in clinical isolates of
      Pseudomonas aeruginosa.
AB  - Lactoferrin, a multifunctional protein with antimicrobial activity, is a
      component of the innate immune system. It may possibly prevent clinical isolates
      of Pseudomonas aeruginosa from developing biofilm, but this hypothesis is yet to
      be widely accepted. We evaluated the in vitro effects of lactoferrin on biofilm
      formation by various clinical isolates of P. aeruginosa using a modified method
      of the microtiter plate biofilm assay. Lactoferrin significantly inhibited
      biofilm formation in these isolates. The effect was the most marked at 2 mg/ml,
      which suggested that an optimal concentration of lactoferrin might exist.
      Lactoferrin inhibited biofilm formation in eight of nine clinical isolates after
      1 day of incubation; however, the inhibitory effects were maintained until 7 days
      of incubation in only two of those eight strains. Suppression of biofilm
      formation may be caused by a mechanism that is independent of the bactericidal
      effects of lactoferrin because the number of viable bacteria was not influenced
      by lactoferrin under the experimental conditions. Supplementation of lactoferrin
      to preformed biofilm demonstrated a reduction in biofilm, which suggests that
      lactoferrin may have a destructive effect on biofilm. Pretreatment with ferric
      chloride partially restored biofilm formation, suggesting an iron-chelating
      action may be involved in the inhibitory mechanism of lactoferrin. These results
      suggest that lactoferrin provides inhibitory effects on biofilm formation in many
      clinical isolates of P. aeruginosa and that it may also have destructive effects
      on preformed biofilm, but further research using multiple clinical strains should
      be undertaken to clarify if those effects are universal.

PMID- 21866305
TI  - ZnT3: a zinc transporter active in several organs.
AB  - The review collects the emerging information about zinc transporter 3 (ZnT3).
      ZnT3 has been associated with Alzheimer's disease, airway diseases and diabetes.
      ZnT3 was discovered and cloned in 1996. Since then, the major interest in the
      protein has been in its ability to transport zinc into pre-synaptic vesicles of
      glutamatergic neurones and its role during the development of amyloid beta
      plaques in Alzheimer's disease. Increasing evidence suggests that ZnT3 is present
      in various cell types like different cell types in the brain, cells from adipose
      tissue, beta-cells from pancreatic islets, epithelial cells, cells from testis,
      prostate cancer cells and cells from retina. The expression of ZnT3 is regulated
      by age, hormones, fatty acids, zinc chelation, and glucose.

PMID- 21866306
TI  - Career satisfaction in primary care: a comparison of international and US medical
      graduates.
AB  - BACKGROUND: International medical graduates (IMGs) have substantial
      representation among primary care physicians in the USA and consistently report
      lower career satisfaction compared with US medical graduates (USMGs). Low career
      satisfaction has adverse consequences on physician recruitment and retention.
      OBJECTIVE: This study aims to identify factors that may account for or explain
      lower rates of career satisfaction in IMGs compared with USMGs. DESIGN: Using
      data from the 2008 Health Tracking Physician Survey, a nationally representative
      survey, we examined the association between IMG status and career satisfaction
      among primary care physicians. We used multivariable logistic regression modeling
      to adjust for a broad range of potential explanatory factors and physician
      characteristics. PARTICIPANTS: The study participants comprise primary care
      physicians who reported at least 20 h a week of direct patient care activities (N
      = 1,890). MAIN MEASURES: The main measures include respondents' overall
      satisfaction with their careers in medicine. KEY RESULTS: IMGs were statistically
      significantly less likely than USMGs to report career satisfaction (75.7% vs.
      82.3%; p = 0.005). This difference persisted after adjusting for physician
      characteristics and variables describing the practice environment (adjusted odds
      ratio = 0.62; 95% confidence interval, 0.43-0.90). Pediatricians (vs. internists)
      and those who earned $200,001-250,000 (vs. <$100,000) or >$250,000 were more
      likely to report career satisfaction, while solo practitioners and those who
      reported being unable to provide high-quality patient care were less likely to
      report career satisfaction. CONCLUSIONS: After adjusting for a number of
      variables previously shown to have an impact on career satisfaction, we were
      unable to identify additional factors that could account for or explain
      differences in career satisfaction between IMGs and USMGs. In light of the
      central role of IMGs in primary care, the potential impact of poorer satisfaction
      among IMGs may be substantial. Improved understanding of the causes of this
      differential satisfaction is important to appropriately support the primary care
      physician workforce.

PMID- 21866308
TI  - The alterations in hepatic microcirculation and Kupffer cell activity after
      biliary drainage in jaundiced mice.
AB  - BACKGROUND/PURPOSE: The aim of this study is to examine the effects of biliary
      drainage on hepatic microcirculation and Kupffer cell activity in the liver with
      obstructive jaundice. METHODS: Common bile duct ligation and division was
      performed on C57BL/6 mice to induce obstructive jaundice. Seven or 14 days after
      surgery, some mice underwent biliary drainage. Three days after biliary drainage,
      sinusoidal perfusion, leukocyte rolling and sticking in the postsinusoidal
      venules, and the diameters of sinusoids containing blood flow were evaluated
      using intravital microscopy. Kupffer cell phagocytic activity was estimated as
      the ratio of Kupffer cells that phagocytosed fluorescent-labeled particles to
      sinusoids containing blood flow. RESULTS: Sinusoidal perfusion after biliary
      drainage was significantly increased compared with that in livers with
      obstructive jaundice, but remained decreased compared with controls. Although the
      number of rolling leukocytes and sticking leukocytes was significantly decreased,
      the diameters of sinusoids remained reduced, associated with an increase in
      Kupffer cell phagocytic activity compared with controls even after biliary
      drainage. CONCLUSIONS: Leukocyte-endothelial cell interaction is ameliorated but
      sinusoids remain narrowed due to swelling of activated Kupffer cells; this might
      cause deterioration of hepatic microcirculation during the early phase of biliary
      drainage.

PMID- 21866309
TI  - Hepatic venous outflow reconstruction using an external iliac vein graft for
      hepatic malignancies (with video).
AB  - BACKGROUND: Hepatic venous outflow reconstruction after major hepatectomy for
      advanced hepatic malignancies is often difficult even for experienced surgeons
      because of difficulties in application of anastomotic techniques and selection of
      the appropriate graft. We present our approach to hepatic venous reconstruction
      using an external iliac vein (EIV) graft for patients with hepatic malignancies.
      METHODS: The EIV graft was preoperatively assessed using three-dimensional
      abdominal multidetector computed tomography (MDCT). The EIV graft (3.5-4.5 cm)
      was harvested extraperitoneally through an upper groin incision. First, the
      inferior vena cava and the EIV graft were sutured at two separate sites by using
      6/0 propolypropylene as a traction suture with an operating loupe (*2.5) under
      hemi-hepatic portal inflow occlusion. The distal end of the right hepatic vein
      (HV) was then reconstructed using the same technique. Graft patency was confirmed
      by intraoperative color Doppler ultrasonography (Aloca SSD2000, Japan). RESULTS:
      The mean reconstruction time was 34 +/- 6 min. There were no complications
      related to the HV reconstruction and no mortality. Follow-up MDCT showed patency
      of the graft in all cases without noticeable caliber change. CONCLUSIONS: The EIV
      graft for hepatic venous outflow reconstruction during hepatic resection is a
      simple technique with long-term graft patency for major HV reconstruction.

PMID- 21866310
TI  - Highly osteogenic PDL stem cell clones specifically express elevated levels of
      ICAM1, ITGB1 and TERT.
AB  - Cells derived from the periodontal ligament (PDL) have previously been reported
      to have stem cell-like characteristics (PDL stem cells; PDLSCs) and play an
      important part in bone engineering, including that of alveolar bone. However,
      these populations have been heterogeneous, and thus far no specific marker has
      yet been established from adult human stem cells derived from PDL tissue. We have
      previously isolated highly purified single cell-derived PDLSC clones and
      delineated their phenotypic and functional characteristics. In this report, we
      further obtained three homogeneous and distinct PDLSC clones demonstrating low,
      moderate and high mineralized matrix forming ability-namely PC12, PC4 and PC3,
      respectively, and the expression of mesenchymal stem cell pathway-specific genes
      in these clones was investigated. PCR array revealed that the expression of
      intercellular adhesion molecule 1 (ICAM1), integrin beta 1 (ITGB1) and telomerase
      reverse transcriptase (TERT) was associated with highly osteogenic PDLSC clones,
      as determined by the expression of key osteoblastic markers and their ability to
      form alizarin red S positive mineralized matrix in vitro. The present results
      suggest that these three mesenchymal stem cell-associated markers could
      potentially be used to isolate PDLSCs with high osteogenic capability for
      engineering new bone.

PMID- 21866311
TI  - Efficiency of PlasmocinTM on various mammalian cell lines infected by mollicutes
      in comparison with commonly used antibiotics in cell culture: a local experience.
AB  - Mycoplasma contamination is a deleterious event for cell culture laboratories.
      PlasmocinTM is used to prevent and eradicate mycoplasma infections from cell. In
      this study, 80 different mammalian cell lines from various sources; human,
      monkey, mice, hamster and rat were used to study and evaluate plasmocinTM
      efficiency and compare it to commonly used antibiotics such as BM-cyclin,
      ciprofloxacin and mycoplasma removal agent (MRA). It was shown that mycoplasma
      infections were eradicated by plasmocinTM, BM-cyclin, ciprofloxacin and MRA in
      65%, 66.25%, 20%, and 31.25%, respectively, of infected cell cultures. However,
      re-infection with mycoplasmas after the period of 4 months occurred in 10-80% of
      the studied cell lines. Cell cytotoxicity and culture death was observed in 25,
      17.5 and 10% of the treated cells, for plasmocinTM, BM-cyclin and MRA,
      respectively. In this study, PlasmocinTM showed strong ability to eradicate
      mollicutes from our cell lines with minimal percentage of regrowth. However, due
      to its high cell cytotoxicity it should be used with caution especially when
      dealing with expensive or hard-to-obtain cell lines. Amongst the antibiotics
      tested, BM-cyclin was shown to remove mycoplasma with the highest efficiency.

PMID- 21866312
TI  - In vitro expansion of human adipose-derived stem cells in a spinner culture
      system using human extracellular matrix powders.
AB  - Stem cell therapy requires large numbers of stem cells to replace damaged
      tissues, but only limited numbers of stem cells can be harvested from a single
      patient. To obtain large quantities of stem cells with differentiation potential,
      we explored a spinner culture system using human extracellular matrix (hECM)
      powders. The hECM was extracted from adipose tissue and fabricated into powders.
      Human adipose-derived stem cells (hASCs) were isolated, seeded on hECM powders,
      and cultivated in a spinner flask. The 3-D culture system, using hECM powders,
      was highly effective for promoting cell proliferation. The number of hASCs in the
      3-D culture system significantly increased for 10 days, resulting in an
      approximately 10-fold expansion, whereas a traditional 2-D culture system showed
      just a 2.8-fold expansion. Surface markers, transcriptional factors, and
      differentiation potential of hASCs were assayed to identify the characteristics
      of proliferated cells in 3-D culture system. The hASCs expressed the pluripotency
      markers, Oct-4 and Sox-2 during 3-D culture and retained their capacity to
      differentiate into adipogenic, osteogenic, and chondrogenic lineages. These
      findings demonstrate that the 3-D culture systems using hECM powders provide an
      efficient in vitro environment for stem cell proliferation, and could act as stem
      cell delivery carriers for autologous tissue engineering and cell therapy.

PMID- 21866313
TI  - Regulation of endothelial cell plasticity by TGF-beta.
AB  - Recent evidence has demonstrated that endothelial cells can have a remarkable
      plasticity. By a process called Endothelial-to-Mesenchymal Transition (EndMT)
      endothelial cells convert to a more mesenchymal cell type that can give rise to
      cells such as fibroblasts, but also bone cells. EndMT is essential during
      embryonic development and tissue regeneration. Interestingly, it also plays a
      role in pathological conditions like fibrosis of organs such as the heart and
      kidney. In addition, EndMT contributes to the generation of cancer associated
      fibroblasts that are known to influence the tumor-microenvironment favorable for
      the tumor cells. EndMT is a form of the more widely known and studied Epithelial
      to-Mesenchymal Transition (EMT). Like EMT, EndMT can be induced by transforming
      growth factor (TGF)-beta. Indeed many studies have pointed to the important role
      of TGF-beta receptor/Smad signaling and downstream targets, such as Snail
      transcriptional repressor in EndMT. By selective targeting of TGF-beta receptor
      signaling pathological EndMT may be inhibited for the therapeutic benefit of
      patients with cancer and fibrosis.

PMID- 21866314
TI  - Comparative effect of FGF2, synthetic peptides 1-28 N-POMC and ACTH on
      proliferation in rat adrenal cell primary cultures.
AB  - There is evidence that pro-opiomelanocortin (POMC)-derived peptides other than
      adrenocorticotropic hormone (ACTH) have a role in adrenal cell proliferation. We
      compared the activity of synthetic rat N-terminal POMC fragment 1-28 with
      disulfide bridges (N-POMC(w)) and without disulfide bridges (N-POMC(w/o)), with
      the activity of fibroblast growth factor (FGF2), a widely studied adrenal growth
      factor, and ACTH, in well-characterized pure cultures of both isolated adrenal
      Glomerulosa (G) and Fasciculata/Reticularis (F/R) cells. Three days of FGF2
      treatment had a proliferative effect similar to serum, and synthetic peptide N
      POMC(w) induced proliferation more efficiently than N-POMC(w/o). Moreover, both
      induced proliferation via the ERK1/2 pathway. In contrast, sustained ACTH
      treatment decreased proliferation and viability through apoptosis induction, but
      not necrosis, and independently of PKA and PKC pathways. Further elucidation of 1
      28 POMC signal transduction is of interest, and primary cultures of adrenal cells
      were found to be useful for examining the trophic activity of this peptide.

PMID- 21866315
TI  - Quantum chemical modeling of the kinetic isotope effect of the carboxylation step
      in RuBisCO.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the most important
      enzyme for the assimilation of carbon into biomass, features a well-known isotope
      effect with regards to the CO(2) carbon atom. This kinetic isotope effect alpha =
      k(12)/k(13) for the carboxylation step of the RuBisCO reaction sequence, and its
      microscopic origin, was investigated with the help of cluster models and quantum
      chemical methods [B3LYP/6-31G(d,p)]. We use a recently proposed model for the
      RuBisCO active site, in which a water molecule remains close to the reaction
      center during carboxylation of ribulose-1,5-bisphosphate [B. Kannappan, J.E.
      Gready, J. Am. Chem. Soc. 130 (2008), 15063]. Alternative active-site models
      and/or computational approaches were also tested. An isotope effect alpha for
      carboxylation is found, which is reasonably close to the one measured for the
      overall reaction, and which originates from a simple frequency shift of the
      bending vibration of (12)CO(2) compared to (13)CO(2). The latter is the dominant
      mode for the product formation at the transition state.

PMID- 21866316
TI  - Molecular dynamics simulations of the Bcl-2 protein to predict the structure of
      its unordered flexible loop domain.
AB  - B-cell lymphoma (Bcl-2) protein is an anti-apoptotic member of the Bcl-2 family.
      It is functionally demarcated into four Bcl-2 homology (BH) domains: BH1, BH2,
      BH3, BH4, one flexible loop domain (FLD), a transmembrane domain (TM), and an X
      domain. Bcl-2's BH domains have clearly been elucidated from a structural
      perspective, whereas the conformation of FLD has not yet been predicted, despite
      its important role in regulating apoptosis through its interactions with JNK-1,
      PKC, PP2A phosphatase, caspase 3, MAP kinase, ubiquitin, PS1, and FKBP38. Many
      important residues that regulate Bcl-2 anti-apoptotic activity are present in
      this domain, for example Asp34, Thr56, Thr69, Ser70, Thr74, and Ser87. The
      structural elucidation of the FLD would likely help in attempts to accurately
      predict the effect of mutating these residues on the overall structure of the
      protein and the interactions of other proteins in this domain. Therefore, we have
      generated an increased quality model of the Bcl-2 protein including the FLD
      through modeling. Further, molecular dynamics (MD) simulations were used for FLD
      optimization, to predict the flexibility, and to determine the stability of the
      folded FLD. In addition, essential dynamics (ED) was used to predict the
      collective motions and the essential subspace relevant to Bcl-2 protein function.
      The predicted average structure and ensemble of MD-simulated structures were
      submitted to the Protein Model Database (PMDB), and the Bcl-2 structures obtained
      exhibited enhanced quality. This study should help to elucidate the structural
      basis for Bcl-2 anti-apoptotic activity regulation through its binding to other
      proteins via the FLD.

PMID- 21866317
TI  - Molecular modeling approach to predict a binding mode for the complex
      methotrexate-carboxypeptidase G2.
AB  - Carboxypeptidase G(2) (CPG(2)) is a zinc-metalloenzyme employed in a range of
      cancer chemotherapy strategies by activating selectively nontoxic prodrugs into
      cytotoxic drugs in tumor as well as in the treatment of intoxication caused by
      high-doses of the anticancer drug methotrexate (MTX). CPG(2) catalyzes the
      hydrolytic cleavage of C-terminal of glutamate moiety from folic acid and
      analogues. Regardless of its extensive application, its mechanism of catalysis
      has not yet been determined and, so far, no co-crystallized complex has been
      published. So, in this study, molecular docking and a short molecular dynamics
      (MD) simulation sampling scheme, as a function of temperature, were performed to
      investigate a possible binding mode for MTX, a recognized substrate of CPG(2).
      The findings suggested that MTX interacts possibly in quite specific points of
      the CPG(2) active site, which are probably responsible for the molecular
      recognition and cleavage procedures. The MTX substrate fits well in the catalytic
      site by accommodating the pteridine moiety in an adjacent pocket to the active
      site whereas a glutamate moiety is pointed toward the protein surface.
      Additionally, a glutamate residue can interact with a crystallization water
      molecule in the active site, supporting its activation as a nucleophilic group.

PMID- 21866318
TI  - Release of beryllium from mineral ores in artificial lung and skin surface
      fluids.
AB  - Exposure to some manufactured beryllium compounds via skin contact or inhalation
      can cause sensitization. A portion of sensitized persons who inhale beryllium may
      develop chronic beryllium disease (CBD). Little is understood about exposures to
      naturally occurring beryllium minerals. The purpose of this study was to assess
      the bioaccessibility of beryllium from bertrandite ore. Dissolution of
      bertrandite from two mine pits (Monitor and Blue Chalk) was evaluated for both
      the dermal and inhalation exposure pathways by determining bioaccessibility in
      artificial sweat (pH 5.3 and pH 6.5), airway lining fluid (SUF, pH 7.3), and
      alveolar macrophage phagolysosomal fluid (PSF, pH 4.5). Significantly more
      beryllium was released from Monitor pit ore than Blue Chalk pit ore in artificial
      sweat buffered to pH 5.3 (0.88 +/- 0.01% vs. 0.36 +/- 0.00%) and pH 6.5 (0.09 +/-
      0.00% vs. 0.03 +/- 0.01%). Rates of beryllium released from the ores in
      artificial sweat were faster than previously measured for manufactured forms of
      beryllium (e.g., beryllium oxide), known to induce sensitization in mice. In SUF,
      levels of beryllium were below the analytical limit of detection. In PSF,
      beryllium dissolution was biphasic (initial rapid diffusion followed by latter
      slower surface reactions). During the latter phase, dissolution half-times were
      1,400 to 2,000 days, and rate constants were ~7 * 10(-10) g/(cm(2).day),
      indicating that bertrandite is persistent in the lung. These data indicate that
      it is prudent to control skin and inhalation exposures to bertrandite dusts.

PMID- 21866319
TI  - Field environmental geochemistry for soil, sediment and groundwater. Preface.

PMID- 21866320
TI  - Ascorbate and thiol antioxidants abolish sensitivity of yeast Saccharomyces
      cerevisiae to disulfiram.
AB  - Sensitivity of baker's yeast to disulfiram (DSF) and hypersensitivity of a mutant
      devoid of Cu, Zn-superoxide dismutase to this compound is reported, demonstrating
      that yeast may be a simple convenient eukaryotic model to study the mechanism of
      DSF toxicity. DSF was found to induce oxidative stress in yeast cells
      demonstrated by increased superoxide production and decrease of cellular
      glutathione content. Anoxic atmosphere and hydrophilic antioxidants (ascorbate,
      glutathione, dithiothreitol, cysteine, and N-acetylcysteine) ameliorated DSF
      toxicity to yeast indicating that oxidative stress plays a critical role in the
      cellular action of DSF.

PMID- 21866322
TI  - Osteosclerotic lesions in patients treated with gefitinib for lung
      adenocarcinomas: a sign of favorable therapeutic response.
AB  - OBJECTIVE: To assess the frequency of osteosclerotic changes on CT that appeared
      after treatment with gefitinib in patients with lung adenocarcinoma and the
      relationship between the osteosclerotic changes and the response to the therapy.
      MATERIALS AND METHODS: Our study included 41 patients with lung adenocarcinoma
      who underwent chest CT both before (CTpre) and after (CTpost) starting treatment
      with gefitinib. The presence or absence of bone metastases was assessed on the
      CTpre, and the interval bony change after the therapy was classified as lytic,
      sclerotic, or no changes on the CTpost. The relationship between treatment
      results of primary lung cancer and interval bony changes was evaluated. RESULTS:
      Osteosclerotic lesions were identified in 11 patients (27%) on CTpost; in 6 of 11
      patients osteosclerotic lesions newly appeared where the CTpre showed no bone
      metastasis before the gefitinib therapy. There were significant differences in
      the therapeutic response of the primary cancers (P < 0.001) and in the survival
      rate (P < 0.01) in patients with osteosclerotic changes versus those without
      osteosclerotic changes. CONCLUSION: Osteosclerotic changes on CT, observed after
      gefitinib treatment in patients with lung adenocarcinomas, may be an indicator of
      a good therapeutic response.

PMID- 21866321
TI  - The immune microenvironment of myeloma.
AB  - The bone marrow (BM) is the site of disease in myeloma and possesses unique
      immune characteristics involved in the pathobiology of the disease. Interactions
      of plasma cells with stromal cells, osteoclasts, osteoblasts, myeloid and
      lymphoid cells make up the unique bone marrow milieu that mediates myeloma
      disease progression. Independently or through a complex network of interactions
      these cells impart immune changes leading to immune evasion and disease
      progression. The critical role of these factors in disease progression has led to
      the intense development of therapeutic strategies aimed at either disrupting the
      immune mechanisms mediating disease progression or augmenting those with anti
      tumor benefits. This review discusses the major contributors of immunity in the
      bone marrow microenvironment, their interactions, and mechanisms whereby immune
      modulation can be translated into therapies with anti-myeloma efficacy.

PMID- 21866323
TI  - Evaluation of the Determine Syphilis TP assay for the detection of antibodies
      against Treponema pallidum for the serodiagnosis of syphilis.
AB  - Currently, infectious syphilis has been resurgent in China and has become a
      significant public health problem. The rapid expansion of syphilis screening
      programs is urgently required. In the present study, the performance of the
      Determine Syphilis TP assay (Determine TP assay) for the detection of antibodies
      against Treponema pallidum (T. pallidum) for syphilis serodiagnosis was
      evaluated. In total, 300 serum samples were tested for the presence of treponemal
      specific antibodies using the Treponema pallidum particle agglutination (TPPA)
      assay, the Determine TP assay, and the InTec immunochromatography assay (InTec
      assay). The Determine TP assay detected 99, 11, and 5 positive results, whereas
      the InTec assay detected 97, 3, and 3 positive samples from group I (100 TPPA
      positive sera), group II (13 TPPA 1:80 +/- sera), and group III (187 TPPA
      negative sera), respectively. The sensitivity, specificity, and the rate
      concordant with TPPA for the Determine TP assay were 97.35, 98.91, and 97.33%,
      respectively. In comparison to the TPPA, the Determine TP assay is simple to
      perform and time-saving, making it a favorable alternative for the detection of
      T. pallidum-specific antibodies where other T. pallidum-specific confirmatory
      tests are not available. In addition, this rapid treponemal test promotes prompt
      treatment for syphilis by providing early laboratory diagnosis.

PMID- 21866324
TI  - A comparison of the Sensititre(r) MYCOTB panel and the agar proportion method for
      the susceptibility testing of Mycobacterium tuberculosis.
AB  - The agar proportion method (APM) for determining Mycobacterium tuberculosis
      susceptibilities is a qualitative method that requires 21 days in order to
      produce the results. The Sensititre method allows for a quantitative assessment.
      Our objective was to compare the accuracy, time to results, and ease of use of
      the Sensititre method to the APM. 7H10 plates in the APM and 96-well microtiter
      dry MYCOTB panels containing 12 antibiotics at full dilution ranges in the
      Sensititre method were inoculated with M. tuberculosis and read for colony
      growth. Thirty-seven clinical isolates were tested using both methods and 26
      challenge strains of blinded susceptibilities were tested using the Sensititre
      method only. The Sensititre method displayed 99.3% concordance with the APM. The
      APM provided reliable results on day 21, whereas the Sensititre method displayed
      consistent results by day 10. The Sensititre method provides a more rapid,
      quantitative, and efficient method of testing both first- and second-line drugs
      when compared to the gold standard. It will give clinicians a sense of the degree
      of susceptibility, thus, guiding the therapeutic decision-making process.
      Furthermore, the microwell plate format without the need for instrumentation will
      allow its use in resource-poor settings.

PMID- 21866325
TI  - Preoperative MRI/MRA for microvascular decompression in trigeminal neuralgia:
      consecutive series of 67 patients.
AB  - BACKGROUND: Microvascular decompression is an accepted treatment for primary
      trigeminal neuralgia. In recent years, efforts have been made to investigate the
      role of preoperative MRI/MRA in selecting patients with neurovascular
      compression. METHODS: Ninety-two consecutive patients underwent a standard
      retrosigmoid craniotomy for microvascular decompression between 2005 and 2009, of
      whom 67 had a preoperative MRI and MRA according to the protocol of our
      department. Operative findings were accurately recorded and compared to MRI/MRA
      results. Follow-up was in the form of telephone interview. RESULTS: Preoperative
      MRI sensitivity was 96%, while specificity was 75% (1 false positive among 4
      patients with negative intra-operative findings). The predictive value of a
      positive MRI/MRA was 98%, while the predictive value of a negative MRI/MRA was
      50%. Fifty-four patients were available for outcome assessment at a mean follow
      up of 3.8 years (range 1-5). Seventy-two percent of patients were pain-free, 9.5%
      had mild residual pain, while 18.5% had a poor outcome (moderate to severe
      residual pain). The correlation between preoperative MRI/MRA and outcome was not
      statistically significant (P = 0.570). CONCLUSIONS: Preoperative MRI has both
      good sensitivity and positive predictive value. Specificity and negative
      predicitve value were limited in this series. No correlation was found between
      preoperative imaging and outcome. Both radiological and clinical criteria are
      important for patient selection.

PMID- 21866326
TI  - Evaluation of a multiple system atrophy model in rats using multitracer microPET.
AB  - BACKGROUND: A double toxin-double lesion strategy is appropriate for mimicking of
      striatonigral degeneration. Because knowledge of human pathology is limited,
      animal models must be well characterized prior to testing of therapeutic
      approaches to treat multiple system atrophy. In double-toxin animal models,
      however, reduced contralateral rotation after apomorphine injection is restored
      within a few weeks via an unknown mechanism; the animals thus revert to PD
      status. We assessed this phenomenon using multitracer microPET and tissue
      staining. METHODS: Five adult male Wistar rats received injections of 6
      hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB), followed 3
      weeks later by injections of quinolinic acid (QA) into the ipsilateral striatum.
      Apomorphine-induced rotation tests were performed 1 week after each injection,
      and 6 and 10 weeks after QA injection. Rotarod tests were performed weekly after
      6-OHDA injection. MSA-p status was characterized by microPET 5 and 10 weeks after
      QA injection using the tracers 2-deoxy-2-[(18)F]-fluoro-D-glucose ([(18)F]-FDG)
      and [(18)F]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([(18)F]
      FP-CIT). Histological changes were evaluated by tyrosine hydroxylase (TH) and
      cresyl violet staining. RESULTS: The numbers of apomorphine-induced rotations
      increased contralaterally after 6-OHDA lesions were created, but decreased
      significantly after QA administration (p = 0.007). Five weeks after QA injection,
      however, contralateral rotation again increased and persisted for 1 month.
      Rotarod rotation differed significantly between the intact and PD states (p <
      0.05), but not between the PD and MSA-p states. MicroPET revealed glucose
      hypometabolism and dopamine transporter (DAT) impairment on the lesioned side of
      the striatum 1 and 2 months after QA lesion surgery. Loss of nigral cells was
      confirmed by TH immunostaining, and striatal atrophy was observed upon cresyl
      violet staining. CONCLUSION: Pathological changes consistent with MSA-p can be
      generated by the double toxin-double lesion method and persist during follow-up.
      Behavioral tests, such as drug-induced rotation and rotarod tests, are not
      appropriate for long-term follow-up in the MSA-p model, suggesting the need for
      development of more appropriate behavioral tests.

PMID- 21866327
TI  - Osteoplastic decompressive craniotomy--an alternative to decompressive
      craniectomy.
AB  - BACKGROUND: In spite of various degrees of brain expansion, decompressive surgery
      is usually carried out using decompressive craniectomy (DC). After craniectomy it
      is necessary to perform cranioplasty, which prolongs hospitalization and is not
      always without complications. Hence, in situations when cranial decompression is
      indicated, but DC would be too radical, we do not remove the bone flap, and we
      perform so-called osteoplastic decompressive craniotomy (ODC). The technique is
      detailed. OBJECTIVE: To demonstrate the effectiveness of ODC. METHODS: Twenty
      patients underwent ODC for brain edema under various pathological conditions. The
      diagnoses were as follows: 13 subdural hematomas, 3 cerebral contusions, 2 middle
      cerebral artery infarcts, 1 epidural hematoma and 1 arteriovenous malformation.
      The effect of ODC was assessed using postoperative ICP monitoring and the midline
      shift on CT. The ICP threshold for the additional removal of the bone flap was 25
      mmHg. Clinical outcome was evaluated 6 months after surgery using the Glasgow
      Outcome Scale (GOS). RESULTS: Postoperative ICP was up to 25 mmHg in 18 patients
      and exceeded 25 mmHg in 2 cases. The mean midline shift on CT was 10 mm
      preoperatively and 3 mm postoperatively. The decompression during ODC was
      sufficient in 18 patients and insufficient in 2 in whom an additional removal of
      the bone flap was performed. Eight survivals had a favorable outcome (GOS 4-5);
      12 patients had an unfavorable outcome (GOS 1-3), and of these, 4 died.
      CONCLUSION: Our limited study shows that ODC is effective in the treatment of
      intracranial hypertension in the selected subgroup of patients in whom DC would
      be too radical. The main advantage of this method is the elimination of further
      cranioplasty.

PMID- 21866328
TI  - Use of long autologous nerve grafts in brachial plexus reconstruction: factors
      that affect the outcome.
AB  - BACKGROUND: Using grafts directed to distal targets in brachial plexus
      reconstruction has the advantage over proximal targets of avoiding axonal
      dispersion. A long graft (more than 10 cm) is needed to reach most distal
      targets. The objective of this article is to identify factors associated with
      good versus poor outcomes in a clinical series of long grafts used for distal
      brachial plexus reconstruction. METHODS: In 34 patients with a flail arm, 47
      sural grafts >10 cm long were followed for >=2 years postoperatively. Surgical
      technique included standard supraclavicular exposure of the proximal brachial
      plexus and its branches, the phrenic nerve and spinal accessory nerve. Distal
      target nerves were exposed via an incision starting at the axilla, following the
      gap between the biceps and triceps. Cases achieving a good result were
      statistically compared against those with a poor result as to the donor
      nerve/root, target nerve, patient age and weight, time from trauma to surgery,
      graft length and long-term rehabilitation quality. FINDINGS: A good outcome was
      observed with 23 grafts (48.9%), but 66.7% of the 30 long grafts done within 6
      months of trauma yielded a good result. Only 1 of 15 patients with the lowest
      quality rehabilitation score experienced a good result (6.6%) versus all 12
      patients with the highest rating (p < 0.001). Trauma-to-surgery time was roughly
      half as long in those with a good result (4.7 vs. 9.0 months, p < 0.001). No
      other inter-group differences were observed. CONCLUSIONS: The results of a series
      of distal brachial plexus target reinnervations with long grafts is presented and
      analyzed. According to them, time from trauma to surgery and an adequate
      postoperative rehabilitation are important predictors of outcome.

PMID- 21866329
TI  - A pragmatic community-based intervention of multimodal physiotherapy plus deep
      water running (DWR) for fibromyalgia syndrome: a pilot study.
AB  - Evidence-based recommendations support the use of multimodal therapy and
      hydrotherapy for fibromyalgia syndrome; however, there is little standardisation
      of such programmes. The aim of the study was to assess the effectiveness of a
      pool-based exercise using deep water running (DWR) as part of a multimodal
      physiotherapy programme for patients with fibromyalgia syndrome. For a non
      randomised clinical study, 44 patients diagnosed with fibromyalgia were recruited
      from primary care. Patients in the experimental group received a multimodal
      programme incorporating pool-based exercise using DWR three times a week for an 8
      week period. The control group received a leaflet containing advice and continued
      with normal activities. Patients were evaluated for physical function
      (Fibromyalgia Impact Questionnaire, FIQ), pain, general health (Short Form-12
      Health Survey) and quality of life (European Quality of Life Scale-5D) pre- and
      post intervention. Statistically significant results were found for the
      experimental group for FIQ total score, incorporating physical function, pain,
      fatigue, stiffness and psychological variables (p < 0.05). Statistically
      significant differences between the experimental group and control were also
      found for general health (p < 0.05) and quality of life (p < 0.05). The results
      of this pilot study and the high level of compliance and adherence and low level
      of attrition suggest that this multimodal programme incorporating DWR is a safe
      and effective intervention for fibromyalgia syndrome that is acceptable to
      patients.

PMID- 21866330
TI  - Temozolomide in relapsed pediatric brain tumors: 14 cases from a single center.
AB  - AIM: Temozolomide is an active drug against gliomas in adults. It also has some
      promising effects in pediatric patients with brain tumors. We have conducted a
      retrospective study to investigate the effectiveness of temozolomide in patients
      with relapsed brain tumors. PATIENTS AND METHODS: The files of 14 children
      treated at our hospital between 2005 and 2010 with the diagnoses of relapsed
      brain tumors were reviewed for pathological characteristics, treatment results,
      and outcomes. RESULTS: The median age at relapse was 8 years (range, 1.08-23;
      F/M, 5/9). Diagnoses included medulloblastoma (n = 5), atypical teratoid rhabdoid
      tumor (n = 2), ependymoma (n = 2), glioneuronal tumor (n = 1), malignant neoplasm
      (n = 1), pontine glioma (n = 1), astrocytoma grade III (n = 1), and glioblastoma
      multiforme (n = 1). All patients except the one with pontine glioma had undergone
      surgical resection, and all had prior adjuvant chemotherapy. Twelve out of 14
      patients had received radiotherapy. The median number of temozolomide courses was
      5.0 (range, 1-24). Objective response rate in our patients was 35.7% (three
      complete responses, one partial response, and one minor response). Stable disease
      achieved in 14.3% of patients and 50% had progressive disease. Median survival
      time was 8 months (range, 1-55). At the end of the study, three patients were
      alive. Hematological toxicity was seen in 30.8% of all courses. CONCLUSIONS:
      Relapsed brain tumors in childhood have an unfavorable prognosis. These data
      suggest that temozolomide might be an active agent against recurrent
      medulloblastoma. Although overall objective response rate was low, further
      multicentric studies with temozolomide may be warranted in children with
      recurrent brain tumors.

PMID- 21866331
TI  - Elevated cardiac oxidative stress in newborn rats from mothers treated with
      atosiban.
AB  - PURPOSE: The purpose of this study was to evaluate the cardiac and cerebral
      oxidative stress in the offspings of pregnant rats treated with oxytocin
      antagonist atosiban. METHODS: Experimentally naive, adult female Wistar-albino
      rats (200-250 g) were mated with adult male rats for copulation. After confirming
      pregnancy, eight gravid rats were then randomly assigned into two equal groups.
      The animals were treated from days 15 to 20 of gestation. One group acted as a
      control group, and received intraperitoneal (i.p.) injections of saline in a
      daily dose volume of 6 mg/kg/day. The second group received 6 mg/kg/day i.p.
      atosiban. On day 21 of gestation, pups were delivered by cesarean. The heart and
      brain tissues of the newborn rats were dissected and sent for the measurement of
      total oxidant status, total antioxitant status and oxidative stress index.
      RESULTS: There was no significant difference in birthweight or in the number of
      pups between two groups. Newborns from atosiban-treated mothers showed
      significantly increased oxidative stress in the plasma and heart tissue than that
      of controls which was confirmed by histological examination (P < 0.05). Oxidative
      stress parameters and histopathological results of the brain tissues of newborns
      were similar between two groups (P > 0.05). CONCLUSION: Oxytocin receptor
      blockage for the treatment of premature delivery may be associated with increased
      fetal morbidity and mortality secondary to the elevated oxidative stress in the
      heart of the newborns.

PMID- 21866332
TI  - Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome.
AB  - INTRODUCTION: Hypothyroidism is associated with pregnancy complications both for
      the mother and progeny and it should be considered in reproductive age. Thyroid
      autoimmunity is stated to be the main cause of hypothyroidism in iodine
      sufficient areas. Polycystic ovary syndrome (PCOS) is known as the most common
      endocrine disorder affecting women in reproductive age. Early diagnosis and
      treatment of hypothyroidism in PCOS may reduce the rate of infertility and
      pregnancy-related morbidity. In the present study we evaluated thyroid
      autoimmunity in PCOS patients. METHODS: Over a period of 12 months, 78 patients
      with PCOS were recruited to this case-control study. Three hundred and fifty age
      matched women were studied as a control group. PCOS was defined according to the
      revised 2003 Rotterdam criteria. Thyroid size was estimated by inspection and
      palpation. Serum thyroid stimulating hormone (TSH), anti-thyroperoxidase antibody
      (anti-TPO Ab), and anti-thyroglobulin antibody (anti-Tg Ab) were measured.
      RESULTS: The mean +/- SD of serum anti-TPO Ab in PCOS patients and subjects in
      the control group was 216 +/- 428 and 131 +/- 364 IU/mL, respectively (P = 0.04).
      Prevalence of goiter in PCOS patients was higher than that in control subjects
      (62.3 vs. 35.7%, P = 0.0001). Serum TSH and anti-Tg Ab in PCOS patients and
      control subjects did not differ significantly. CONCLUSION: In this case-control
      study, anti-thyroid antibodies and goiter prevalence were significantly higher in
      PCOS patients. These data suggest that thyroid exam and evaluation of thyroid
      function and autoimmunity should be considered in such patients.

PMID- 21866333
TI  - Clinical course of cone dystrophy caused by mutations in the RPGR gene.
AB  - BACKGROUND: Mutations in the RPGR gene predominantly cause rod photoreceptor
      disorders with a large variability in clinical course. In this report, we
      describe two families with mutations in this gene and cone involvement. METHODS:
      We investigated an X-linked cone dystrophy family (1) with 25 affected males, 25
      female carriers, and 21 non-carriers, as well as a small family (2) with one
      affected and one unaffected male. The RPGR gene was analyzed by direct
      sequencing. All medical records were evaluated, and all available data on visual
      acuity, color vision testing, ophthalmoscopy, fundus photography, fundus
      autofluorescence, Goldmann perimetry, SD-OCT, dark adaptation, and full-field
      electroretinography (ERG) were registered. Cumulative risks of visual loss were
      studied with Kaplan-Meier product-limit survival analysis. RESULTS: Both families
      had a frameshift mutation in ORF15 of the RPGR gene; family 1 had
      p.Ser1107ValfsX4, and family 2 had p.His1100GlnfsX10. Mean follow up was 13 years
      (SD 10). Virtually all affected males showed reduced photopic and normal scotopic
      responses on ERG. Fifty percent of the patients had a visual acuity of <0.5 at
      age 35 years (SE 2.2), and 75% of the patients was legally blind at age 60 years
      (SE 2.3). Female carriers showed no signs of ocular involvement. CONCLUSIONS:
      This report describes the clinical course and visual prognosis in two families
      with cone dystrophy due to RPGR mutations in the 3' terminal region of ORF15.
      Remarkable features were the consistent, late-onset phenotype, the severe visual
      outcome, and the non-expression in female carriers. Expression of RPGR mutations
      in this particular region appears to be relatively homogeneous and predisposed to
      cones.

PMID- 21866334
TI  - Promises of stem cell therapy for retinal degenerative diseases.
AB  - With the development of stem cell technology, stem cell-based therapy for retinal
      degeneration has been proposed to restore the visual function. Many animal
      studies and some clinical trials have shown encouraging results of stem cell
      based therapy in retinal degenerative diseases. While stem cell-based therapy is
      a promising strategy to replace damaged retinal cells and ultimately cure retinal
      degeneration, there are several important challenges which need to be overcome
      before stem cell technology can be applied widely in clinical settings. In this
      review, different types of donor cell origins used in retinal treatments,
      potential target cell types for therapy, methods of stem cell delivery to the
      eye, assessments of potential risks in stem cell therapy, as well as future
      developments of retinal stem cells therapy, will be discussed.

PMID- 21866335
TI  - Effects of matrine on proliferation and apoptosis of cultured retinoblastoma
      cells.
AB  - BACKGROUND: Extracted from the traditional Chinese medicine of Kushen, matrine is
      an alkaloid with potential anti-neoplastic and anti-inflammatory effects. Here,
      we examined the effect of matrine on proliferation and apoptosis of cultured
      retinoblastoma cells. METHODS: The retinoblastoma cell lines Y79, WERI-RB1 and SO
      RB50 were treated with matrine in increasing concentrations from 0.2-1.1 mg/ml
      for 24 hours, and the cell proliferation rate was measured. The cells were
      exposed to matrine at 50% inhibition concentration (IC50) for 12, 24 and 48
      hours. Cell cycle was analyzed by flow cytometry, concentration of proteins
      regulating cell cycle and apoptosis was determined by Western blot, apoptosis
      rate was measured by TUNEL staining, and cell morphology was assessed by electron
      transmission microscopy. RESULTS: The retinoblastoma cell lines Y79, WERI-RB1 and
      SO-RB50 showed an increased inhibition of cell proliferation with increasing
      matrine concentrations. Applying the IC50 concentration of matrine, the
      alteration of the cell cycle, including a reduced percentage of the S phase, was
      significantly (P < 0.01) associated with a longer treatment time by matrine.
      Correspondingly, the cell-cycle-associated proteins P21 and P27 were up-regulated
      and the protein cyclinD1 was down-regulated. The apoptosis-associated protein Bcl
      2 was down-regulated, and Bax was up-regulated. In a similar manner, the
      apoptosis rate was significantly increased with longer treatment time.
      CONCLUSIONS: Matrine added to cultures of immortalized retinoblastoma cells led
      to a reduced tumor cell proliferation, decreased rate of mitosis and an increased
      tumor cell apoptosis, paralleled by corresponding changes in the proteins
      regulating the cell cycle or apoptosis.

PMID- 21866336
TI  - Relationship between antiretroviral plasma concentration and emergence of HIV-1
      resistance mutations at treatment failure.
AB  - PURPOSE: The relationship between antiretroviral pharmacokinetic exposure and
      acquisition of human immunodeficency virus-1 (HIV-1) drug resistance mutations
      (DRM) is not fully understood. The aim of this study was to investigate whether
      antiretroviral plasma concentration could predict the emergence of DRM at
      treatment failure. METHODS: The study cohort comprised retrospectively selected
      patients with failing antiretroviral regimens for whom a protease inhibitor (PI)
      or non-nucleoside reverse transcriptase inhibitor (NNRTI) trough concentration
      measurement (TDM) had been obtained before failure, a genotypic resistance test
      (GRT1) had been performed before the TDM, and a genotypic resistance test (GRT2)
      had been performed at therapeutic failure. Drug levels were classified as
      undetectable/detectable or subtherapeutic/therapeutic according to limits of
      quantification of a high-performance liquid chromatography-ultraviolet assay or
      pre-defined efficacy thresholds, respectively. The number of DRM acquired at
      treatment failure was evaluated by comparing the results of the GRT2 and GRT1.
      RESULTS: A total of ten and 57 failure episodes occurred among our patients on
      NNRTI-based and PI-based regimens, respectively, and included in the evaluation.
      PI concentration was subtherapeutic in 28.1% of patients, among which the levels
      were undetectable in 21.1%. Twenty-five (43.9%) patients acquired at least one
      new PI-DRM according to the GRT2. Patients with undetectable PI levels showed a
      lower emergence of PI-DRM (minor + major) than those with detectable levels (8.3
      vs. 53.3%, p = 0.007). Multivariate analysis confirmed that undetectable PI
      levels were independent negative predictors of DRM selection. NNRTI measurements
      were subtherapeutic in 2/10 (20%) patients. NNRTI-DRM were acquired by all
      patients regardless of NNRTI levels. CONCLUSIONS: A PI measurement showing
      undetectable drug levels prior to treatment failure predicted the lack of
      emergence of PI-DRM at failure. These results suggest that PI levels can help
      clinicians interpret the reasons for treatment failure and guide the type of
      interventions needed.

PMID- 21866337
TI  - Lactobacillus jensenii bacteremia and endocarditis after dilatation and
      curettage: case report and literature review.

PMID- 21866338
TI  - Clinical spectrum of serious bacterial infections among splenectomized patients
      with hemoglobinopathies in Israel: a 37-year follow-up study.
AB  - PURPOSE: Patients with hemoglobinopathies who undergo splenectomy are at risk for
      invasive infections. The aim of this investigation was to present the clinical
      spectrum of infections in splenectomized patients. METHODS: The study cohort
      comprised 54 splenectomized patients with beta-thalassemia (beta-thalassemic) and
      sickle cell disease. The incidence of serious invasive bacterial infections was
      recorded. All patients received pneumococcal vaccine and all received oral
      prophylactic penicillin. RESULTS: A total of 22 episodes of serious bacterial
      infections were identified in 19 patients among the study cohort of 54
      splenectomized patients (35%). The clinical spectrum included sepsis (10
      patients), bacteremia (8), liver abscess (1), forearm abscess (1), and urinary
      tract infection (2). The most frequent pathogens were Escherichia coli (8 cases),
      Steptococcus pneumoniae (5), and Campylobacter (2). 22 patients with beta
      thalassemia died during the study period: 6 due to bacterial infection and 18 due
      to cardiomyopathy. The time elapsed between splenectomy and S. pneumoniae
      infection was significantly shorter than that between splenectomy and infections
      caused by other pathogens (18 +/- 14 vs. 115 +/- 93 months, respectively; p =
      0.035). CONCLUSIONS: Splenectomized patients with beta thalassemia and sickle
      cell disease are predisposed to severe infections, with the majority of these
      infections being caused by Gram-negative microorganisms. The attending
      physician(s) should take these findings into consideration when deciding upon an
      empiric antibiotic treatment for splenectomized patients who present with fever
      or sepsis.

PMID- 21866339
TI  - Acute rheumatic fever in the Central Anatolia Region of Turkey: a 30-year
      experience in a single center.
AB  - The study was carried out in Dr. Sami Ulus Children's Hospital to investigate and
      to compare the incidence and findings of acute rheumatic fever patients (ARF)
      seen in the past 30 years. The medical records of 1,115 patients with ARF
      admitted to Dr. Sami Ulus Children's Hospital Department of Pediatric Cardiology
      during 1980-2009 were retrospectively analyzed. Twenty-one percent of those
      patients were admitted between 1980 and 1989, 44.6% between 1990 and 1999, and
      34.2% between 2000 and 2009. The highest incidence was detected in the second
      decade with a rate of 60.0:100,000. Male/female ratio was 1:18. The age of
      patients ranged between 2 and 15 years. Carditis was detected in 64.7% of
      patients, arthritis in 59.1%, and chorea in 14.1%. Mitral regurgitation was the
      most common echocardiographic finding. Heart failure was detected in 13.8%.
      Recurrent attacks occurred in 8.1% of patients. The median follow-up was 6.8
      years (range, 1.2-10.5 years). The prevalence of chronic rheumatic valvular
      disease was 58%. Mortality rate was 0.8%. CONCLUSION: Although the incidence of
      ARF has decreased in the last decade, it still continues to be an important
      public health problem in Turkish pediatric population.

PMID- 21866341
TI  - Expression of cefF significantly decreased deacetoxycephalosporin C formation
      during cephalosporin C production in Acremonium chrysogenum.
AB  - Deacetoxycephalosporin C (DAOC) is not only the precursor but also one of the by
      products during cephalosporin C (CPC) biosynthesis. One enzyme (DAOC/DAC
      synthase) is responsible for the two-step conversion of penicillin N into
      deacetylcephalosporin C (DAC) in Acremonium chrysogenum, while two enzymes (DAOC
      synthase and DAOC hydroxylase) were involved in this reaction in Streptomyces
      clavuligerus and Amycolatopsis lactamdurans (Nocardia lactamdurans). In this
      study, the DAOC hydroxylase gene cefF was cloned from Streptomyces clavuligerus
      and introduced into Acremonium chrysogenum through Agrobacterium tumefaciens
      mediated transformation. When cefF was expressed under the promoter of pcbC, the
      ratio of DAOC/CPC in the fermentation broth significantly decreased. These
      results suggested that introduction of cefF could function quite well in
      Acremonium chrysogenum and successfully reduce the content of DAOC in the CPC
      fermentation broth. This work offered a practical way to improve the CPC
      purification and reduce its production cost.

PMID- 21866343
TI  - The 18p11.22 locus is associated with never smoker non-small cell lung cancer
      susceptibility in Korean populations.
AB  - The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is
      about 30-40%. Despite the striking demographics and high prevalence of never
      smoker NSCLC, the exact causes still remain undetermined. Although several genome
      wide association (GWA) studies were conducted to find susceptibility loci for
      lung cancer in never smokers, no regions were replicated except for 5p15.33,
      suggesting locus heterogeneity and different environmental toxic effects. To
      identify genetic loci associated with susceptibility of lung cancer in never
      smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For
      discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and
      497 normal subjects. We tested association of SNPs with lung cancer
      susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs
      were selected from the top 50 SNPs and five additional SNPs were selected in the
      DAB1 gene region which showed significant associations in the GWA analysis. The
      validation SNPs were genotyped in an independent sample including 434 patients
      and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and
      rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were
      replicated. P value of rs11080466 was 1.08 * 10(-6) in the combined sets (2.68 *
      10(-5) in the discovery set and 2.60 * 10(-3) in the validation set) and odds
      ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our
      result suggests the 18p11.22 region as a novel lung cancer susceptibility locus
      in never smokers.

PMID- 21866344
TI  - Isolation and characterization of a novel ammonium overly sensitive mutant,
      amos2, in Arabidopsis thaliana.
AB  - Ammonium (NH(4)(+)) toxicity is a significant agricultural problem globally,
      compromising crop growth and productivity in many areas. However, the molecular
      mechanisms of NH(4)(+) toxicity are still poorly understood, in part due to a
      lack of valuable genetic resources. Here, a novel Arabidopsis mutant, amos2
      (ammonium overly sensitive 2), displaying hypersensitivity to NH(4) (+) in both
      shoots and roots, was isolated. The mutant exhibits the hallmarks of NH(4)(+)
      toxicity at significantly elevated levels: severely suppressed shoot biomass,
      increased leaf chlorosis, and inhibition of lateral root formation. Amos2
      hypersensitivity is associated with excessive NH(4)(+) accumulation in shoots and
      a reduction in tissue potassium (K(+)), calcium (Ca(2+)), and magnesium (Mg(2+)).
      We show that the lesion is specific to the NH(4)(+) ion, is independent of
      NH(4)(+) metabolism, and can be partially rescued by elevated external K(+). The
      amos2 lesion was mapped to a 16-cM interval on top of chromosome 1, where no
      similar mutation has been previously mapped. Our study identifies a novel locus
      controlling cation homeostasis under NH(4)(+) stress and provides a tool for the
      future identification of critical genes involved in the development of NH(4)(+)
      toxicity.

PMID- 21866342
TI  - Ion channels and schizophrenia: a gene set-based analytic approach to GWAS data
      for biological hypothesis testing.
AB  - Schizophrenia is a complex genetic disorder. Gene set-based analytic (GSA)
      methods have been widely applied for exploratory analyses of large, high
      throughput datasets, but less commonly employed for biological hypothesis
      testing. Our primary hypothesis is that variation in ion channel genes contribute
      to the genetic susceptibility to schizophrenia. We applied Exploratory Visual
      Analysis (EVA), one GSA application, to analyze European-American (EA) and
      African-American (AA) schizophrenia genome-wide association study datasets for
      statistical enrichment of ion channel gene sets, comparing GSA results derived
      under three SNP-to-gene mapping strategies: (1) GENIC; (2) 500-Kb; (3) 2.5-Mb and
      three complimentary SNP-to-gene statistical reduction methods: (1) minimum p
      value (pMIN); (2) a novel method, proportion of SNPs per Gene with p values below
      a pre-defined alpha-threshold (PROP); and (3) the truncated product method (TPM).
      In the EA analyses, ion channel gene set(s) were enriched under all mapping and
      statistical approaches. In the AA analysis, ion channel gene set(s) were
      significantly enriched under pMIN for all mapping strategies and under PROP for
      broader mapping strategies. Less extensive enrichment in the AA sample may
      reflect true ethnic differences in susceptibility, sampling or case ascertainment
      differences, or higher dimensionality relative to sample size of the AA data.
      More consistent findings under broader mapping strategies may reflect enhanced
      power due to increased SNP inclusion, enhanced capture of effects over extended
      haplotypes or significant contributions from regulatory regions. While extensive
      pMIN findings may reflect gene size bias, the extent and significance of PROP and
      TPM findings suggest that common variation at ion channel genes may capture some
      of the heritability of schizophrenia.

PMID- 21866345
TI  - Elevated DeltapH restores rapidly reversible photoprotective energy dissipation
      in Arabidopsis chloroplasts deficient in lutein and xanthophyll cycle activity.
AB  - The xanthophylls of the light-harvesting complexes of photosystem II (LHCII),
      zeaxanthin, and lutein are thought to be essential for non-photochemical
      quenching (NPQ). NPQ is a process of photoprotective energy dissipation in
      photosystem II (PSII). The major rapidly reversible component of NPQ, qE, is
      activated by the transmembrane proton gradient, and involves the quenching of
      antenna chlorophyll excited states by the xanthophylls lutein and zeaxanthin.
      Using diaminodurene (DAD), a mediator of cyclic electron flow around photosystem
      I, to enhance DeltapH we demonstrate that qE can still be formed in the absence
      of lutein and light-induced formation of zeaxanthin in chloroplasts derived from
      the normally qE-deficient lut2npq1 mutant of Arabidopsis. The qE induced by high
      DeltapH in lut2npq1 chloroplasts quenched the level of fluorescence when all PSII
      reaction centers were in the open state (F (o) state), protected PSII reaction
      centers from photoinhibition, was sensitive to the uncoupler nigericin, and was
      accompanied by absorption changes in the 410-565 nm region. Titrations show the
      DeltapH threshold for activation of qE in lut2npq1 chloroplasts lies outside the
      normal physiological range and is highly cooperative. Comparison of quenching in
      isolated trimeric (LHCII) and monomeric (CP26) light-harvesting complexes from
      lut2npq1 plants revealed a similarly shifted pH dependency compared with wild
      type LHCII. The implications for the roles of lutein and zeaxanthin as direct
      quenchers of excitation energy are discussed. Furthermore, we argue that the
      control over the proton-antenna association constant, pK, occurs via influence of
      xanthophyll structure on the interconnected phenomena of light-harvesting antenna
      reorganization/aggregation and hydrophobicity.

PMID- 21866347
TI  - The use of the GuideLinerTM catheter as a child-in-mother  technique: an initial
      single-center experience.
AB  - Recently, a new interventional guide catheter, the GuideLinerTM catheter, was
      introduced into the market as a strategy for tackling the problem of stent
      delivery failure. We implemented this simplified child-in-mother technique in a
      series of 16 challenging coronary interventions. Balloon and stent delivery was
      successfully achieved in all cases and the device was both simple to deploy and
      remove. Apart from two cases of vessel dissection that were managed successfully
      with stent implantation, no other serious procedural complications were reported.

PMID- 21866346
TI  - Cloning and characterization of a maize bZIP transcription factor, ZmbZIP72,
      confers drought and salt tolerance in transgenic Arabidopsis.
AB  - In plants, the bZIP (basic leucine zipper) transcription factors regulate diverse
      functions, including processes such as plant development and stress response.
      However, few have been functionally characterized in maize (Zea mays). In this
      study, we cloned ZmbZIP72, a bZIP transcription factor gene from maize, which had
      only one copy in the maize genome and harbored three introns. Analysis of the
      amino acid sequence of ZmbZIP72 revealed a highly conserved bZIP DNA-binding
      domain in its C-terminal region, and four conserved sequences distributed in N-
      or C-terminal region. The ZmbZIP72 gene expressed differentially in various
      organs of maize plants and was induced by abscisic acid, high salinity, and
      drought treatment in seedlings. Subcellular localization analysis in onion
      epidermal cells indicated that ZmbZIP72 was a nuclear protein. Transactivation
      assay in yeast demonstrated that ZmbZIP72 functioned as a transcriptional
      activator and its N terminus (amino acids 23-63) was necessary for the
      transactivation activity. Heterologous overexpression of ZmbZIP72 improved
      drought and partial salt tolerance of transgenic Arabidopsis plants, as
      determined by physiological analyses of leaf water loss, electrolyte leakage,
      proline content, and survival rate under stress. In addition, the seeds of
      ZmbZIP72-overexpressing transgenic plants were hypersensitive to ABA and osmotic
      stress. Moreover, overexpression of ZmbZIP72 enhanced the expression of ABA
      inducible genes such as RD29B, RAB18, and HIS1-3. These results suggest that the
      ZmbZIP72 protein functions as an ABA-dependent transcription factor in positive
      modulation of abiotic stress tolerance and may be a candidate gene with potential
      application in molecular breeding to enhance stress tolerance in crops.

PMID- 21866348
TI  - Influence of energetic status on ontogenetic niche shifts: emergence from the
      redd is linked to metabolic rate in brown trout.
AB  - Ontogenetic niche shift should occur when the ratio of growth opportunities to
      mortality risk becomes higher in the subsequent habitat. While most studies have
      focused on size to understand the timing of these shifts, an endogenous factor
      like energetic status (interaction between energy available and energy
      requirements) appears as a natural candidate to integrate and analyze the growth
      trade-off between habitats. In this study, we measure energetic content and
      metabolic rate of individual brown trout (Salmo trutta) fry at emergence from
      gravel to investigate the influence of energetic status on the timing of this
      critical ontogenetic niche shift. In addition, as offspring energetic status is
      subject to parental effects, we examine how females could maximize their own
      fitness by influencing offspring emergence timing. Our results demonstrate that
      emergence from gravel is influenced by energetic status. Individuals that emerge
      first have a higher energetic content but deplete it faster because of a higher
      metabolic rate. We also find that female fecundity is positively related to
      emergence period duration. Moreover, our results suggest that females may
      decrease kin competition during the critical period of emergence by influencing
      the energetic status of offspring, thus, maximizing their own fitness. Our
      results help elucidate the mechanisms underlying early ontogenetic niche shifts
      in juvenile fish and suggest reasons why maternal investment can be so variable
      within populations.

PMID- 21866349
TI  - Hamstring graft sizes differ between Chinese and Caucasians.
AB  - PURPOSE: The use of hamstring tendon autografts for anterior cruciate ligament
      (ACL) surgery has become more and more common. The purposes of this study were to
      determine whether anthropomorphic measurement correlated with tendon sizes in
      Chinese patient group and whether tendon sizes in Chinese and Caucasian patient
      groups differed. METHODS: From 2008 to 2009, 100 patients that received double
      bundle ACL reconstruction with autologous hamstring tendons were prospectively
      enrolled. The original lengths and triple-folded graft diameters of the
      individual semitendinosus (ST) and gracilis (Gr) tendons were recorded and
      correlated with the anthropometric data (height, weight, body mass index, gender,
      thigh length, shank length, leg length and bilateral thigh circumference) of the
      patients. Later, using height for predictions, the original heights of patients
      were added to the equations previously used for regression models to compare the
      tendon lengths in different ethnic groups. RESULTS: After stepwise multiple
      linear regression analysis, the height and leg lengths showed greatest
      correlation with the lengths of both tendons. The lengths of both the
      semitendinosus and gracilis tendons in Caucasian patients were significantly
      longer than in the Chinese patients. CONCLUSIONS: The results of this study
      showed that anthropomorphic measurements (height and leg length) correlated with
      tendon lengths. In addition, Caucasians had significantly longer hamstring
      tendons than the Chinese patients. LEVEL OF EVIDENCE: Prospective cohort study
      (prevalence), Level I.

PMID- 21866350
TI  - Fracture at the stem-condylar junction of a modular femoral prosthesis in a varus
      valgus constrained total knee arthroplasty.
AB  - We present a rare case of fracture of the modular femoral component in a varus
      valgus constrained total knee arthroplasty (TKA) prosthesis which occurred 2
      years after implantation. Both femoral and tibial components underwent a second
      revision using a constrained hinged TKA. Laboratory analysis revealed
      insufficient metaphyseal bone stock in association with inadequate cement mantle
      incorporation which made implant fixation solely reliant on the intramedullary
      stem construct. It was therefore hypothesized that high repetitive stresses over
      the junction of the modular component led to the fracture. LEVEL OF EVIDENCE:
      Case report, Level IV.

PMID- 21866351
TI  - Mutagenicity of diagnostic and therapeutical doses of radiopharmaceutical iodine
      131 in Wistar rats.
AB  - Iodine-131 ((131)I) is a radioisotope used for the diagnosis and treatment of
      thyroidal disorders such as hyperthyroidism and cancer. During its decay, (131)I
      emits beta particles and gamma rays; its physical half-life is 8 days, and it is
      accumulated preferentially in the thyroid tissue. This study aimed to evaluate
      the cytotoxicity and mutagenicity of diagnostic and therapeutic doses of (131)I
      using bone marrow cells of rats treated in vivo in a test system with a single
      dose by gavage. Concentrations of 5, 25, 50 and 250 MUCi in 1 ml of water were
      used, and after 24 h, the animals were killed. Also, a concentration of 25
      MUCi/ml of water was used, and the animals were killed after 5 days. The results
      showed that no concentration of (131)I was cytotoxic and that all concentrations
      were mutagenic. As a result, there was no statistically significant difference
      detected by the chi(2) test in the induction of chromosomal aberrations between
      the different doses. Thus, the present study demonstrated a significant increase
      in chromosomal aberration in bone marrow cells exposed to (131)I regardless of
      the dose or the treatment time.

PMID- 21866352
TI  - The jornalero: perceptions of health care resources of immigrant day laborers.
AB  - Latino immigrant day laborers, also termed jornaleros or contingent workers,
      compose a significant segment of the millions of undocumented, temporary workers
      in our urban centers. These laborers largely work without benefit of health
      insurance in occupations that are unmonitored, unprotected, and often unsafe.
      This study utilized semi-structured interviews to explore the perceived health
      status and resources for health care in one group of 20 Latino day laborers in
      southern California. Results suggest a population that is largely in undocumented
      immigrant status with few health care resources other than emergency care centers
      and clinics provided for the homeless population. With close to 12 million
      undocumented workers currently residing in the US, this population bears
      additional scrutiny both for humanitarian reasons and for public health policy
      considerations.

PMID- 21866353
TI  - Arthroscopic findings of Kienbock's disease.
AB  - PURPOSE: Kienbock's disease affects the lunate bone, and osteoarthritic changes
      progress as the disease advances; however, relatively few studies have reported
      the arthroscopic findings of Kienbock's disease, and these reports have been in
      small populations. The purpose of this study was to review arthroscopic findings
      in a larger population than studied in previous reports. METHODS: We
      retrospectively reviewed 57 patients who underwent radial osteotomy for
      Kienbock's disease after arthroscopy of both the radiocarpal and midcarpal
      joints. All arthroscopic findings were classified as follows in terms of the
      location of osteoarthritic changes: lunate fossa of the radius, proximal/distal
      surface of the lunate bone, and capitate head. Radiological stages were
      classified according to the modified Lichtman's classification system. RESULTS:
      All but two patients had cartilage lesions in the proximal lunate cartilage.
      Older patients had significantly more cartilage lesions, but radiological stage
      showed no correlation with the number of cartilage lesions. CONCLUSIONS: This
      study demonstrated that the proximal lunate bone was affected in most cases of
      Kienbock's disease and that older patients had more cartilage lesions.

PMID- 21866354
TI  - Reliability and validity of the Western Ontario Shoulder Instability Index (WOSI)
      in the Japanese population.
AB  - BACKGROUND: The Western Ontario Shoulder Instability Index (WOSI) questionnaire
      is a disease-specific self-evaluated measurement tool used for patients with
      shoulder instability. The purpose of this study was to evaluate the reliability
      and validity of the WOSI Japanese version for the Japanese population. METHODS:
      The WOSI Japanese version was prepared by use of several steps including
      translation, back translation, and verification by the author and owner of the
      WOSI. Reliability (internal consistency and reproducibility) and validity were
      then tested for 85 patients with shoulder instability. All patients completed the
      WOSI Japanese version, Quick DASH, and SF-36, and underwent assessment of the
      Rowe rating scale for the purpose of internal consistency and validity. Fifty
      nine of the patients repeated the WOSI 2 weeks after the first examination for
      assessment of test-retest reproducibility. RESULTS: Both internal consistency
      (0.84 for Cronbach's alpha) and reproducibility (Pearson's r = 0.91, intraclass
      correlation coefficient = 0.91) indicated the reliability of the WOSI Japanese
      questionnaire was good. Comparison with the Rowe rating scale (p < 0.001) also
      showed validity was good. The correlation coefficient between the WOSI Japanese
      version and the Quick DASH (Pearson's r = 0.62) was higher than that between the
      WOSI Japanese version and the SF-36 (Pearson's r = 0.10-0.36 for subscales).
      CONCLUSION: The WOSI Japanese questionnaire is a reliable self-assessment tool
      that is comparable with the original English version. We therefore recommend use
      of the WOSI Japanese version when evaluating patients with shoulder instability
      in the Japanese population.

PMID- 21866355
TI  - Acromio-clavicular dislocation with coraco-clavicular ligament clavicular
      avulsion fracture.

PMID- 21866356
TI  - Hearing loss in patients with mucopolysaccharidosis II: data from HOS - the
      Hunter Outcome Survey.
AB  - BACKGROUND: Subjectively reported hearing loss is a common feature of
      mucopolysaccharidosis II (MPS II, Hunter syndrome). This study provides an
      epidemiological description of hearing loss and other otolaryngological
      manifestations reported by patients registered in the Hunter Outcome Survey
      (HOS), an international registry of patients with MPS II. METHODS: Data about ear
      signs and symptoms were available for 554 of the 605 patients alive at HOS entry.
      The degree of hearing loss for 162 pure-tone audiograms (PTAs) from 83 patients
      was classified by independent interpreters using both the age-specific
      International Institute of Standardization (ISO) 7029 standard and the age
      independent World Health Organization (WHO) clinical guidelines. A linear
      regression analysis using cross-sectional data was conducted to investigate the
      relationship between hearing loss and age. RESULTS: The most prevalent
      otolaryngological manifestations and interventions reported were otitis (either
      acute otitis media or chronic otitis media [72%]), hearing loss (67%), insertion
      of ventilation tubes (50%), adenoidectomy (47%), and hearing aids (41%).
      According to the ISO standard, only one patient out of the 83 with audiogram data
      in HOS had normal hearing in both ears at all time points. According to the WHO
      classification, 16% had normal hearing; hearing loss was mild in 24%, moderate in
      31%, severe in 22%, and profound in 7%. In the linear regression analysis, the
      hearing threshold in the cohort increased with age at an estimated rate of
      approximately 1 dB per year. CONCLUSIONS: Hearing impairment is common in MPS II.
      Early otolaryngological evaluation and intervention is recommended.

PMID- 21866357
TI  - Prevalence of and risk factors for subjective symptoms in urban preschool
      children without a cause identified by the guardian.
AB  - OBJECTIVE: The aim of this study was to explore the prevalence of and the risk
      factors for subjective symptoms without an identified cause by the guardian
      (SSWICG) in urban preschool children. METHODS: A questionnaire was used to
      collect information from 661 urban preschool children. The subjective symptoms
      were cited from the MM075NA Indoor Environment Quality Investigation
      Questionnaire. Information about living conditions, kindergarten and outdoor
      environments was collected, as well as health information from each child.
      RESULTS: The prevalence of SSWICG reached 31%, among which the prevalence of
      general symptoms in the central nervous system (CNS) reached 54.6%. Univariate
      analysis showed that the materials that made indoor furniture, walls and doors,
      indoor biological factors, outdoor pollution sources near the house and traffic
      pollution were associated with SSWICG and mucosal, dermal and general symptoms in
      the CNS subgroups. Multivariate analysis also showed that furniture materials,
      traffic pollution, kindergarten environment quality and allergies were
      associated. CONCLUSIONS: The prevalence of SSWICG was relatively high. Possible
      risk factors include indoor furnishing materials, allergy, traffic pollution and
      kindergarten environmental pollution.

PMID- 21866358
TI  - Analysis of the complete DNA sequence of rice tungro bacilliform virus from
      southern India indicates it to be a product of recombination.
AB  - The complete nucleotide sequence of an isolate of rice tungro bacilliform virus
      (RTBV), collected from Kanyakumari, India, where RTBV was reported recently for
      the first time, has been analyzed. Sequence comparison revealed that the RTBV
      isolate from Kanyakumari (RTBV-KK) has a high degree of identity to the two
      previously reported RTBV sequences from India, RTBV-AP and RTBV-WB, which had
      been collected from field locations about 10 years ago and 1000-2000 km away from
      the collection site of RTBV-KK. Most of the sequence domains reported previously
      in other RTBV isolates were found to be conserved in RTBV-KK. Closer inspection
      revealed RTBV-KK to be a possible recombinant between RTBV-AP and RTBV-WB in the
      genomic region encompassing the coat protein gene.

PMID- 21866359
TI  - Use of EPR and FTIR to detect biological effects of ultrasound and microbubbles
      on a fibroblast cell line.
AB  - Structural and functional effects of exposing murine fibroblasts (NIH 3T3) to
      therapeutic ultrasound at 1 MHz frequency are described. These bioeffects can be
      attributed to the formation of free radical species by sonolysis of water. When
      cavitation occurs, dissociation of water vapor into H atoms and OH radicals is
      observed; these H atoms and OH radicals combine to form H(2), H(2)O(2), and
      HO(2). The radicals can chemically modify biomolecules, for example enzymes, DNA,
      and lipids. Generation of free radicals during exposure to ultrasound with or
      without encapsulated microbubbles (contrast agents) was studied by use of
      electron paramagnetic resonance with DMPO spin trapping. Recently the potential
      for possible use of these microbubbles in gene therapy has been investigated,
      because of the ability of the stabilized microbubbles to release their content
      when exposed to ultrasound. Structural changes were studied by Fourier-transform
      infrared spectroscopy, and induction of possible genotoxic damage by exposure of
      the cells to therapeutic ultrasound at 1 MHz frequency with our experimental
      device was verified by use of the cytokinesis-block micronucleus assay.

PMID- 21866360
TI  - Deep inferior epigastric artery perforated rectus abdominis free flap for head
      and neck reconstruction.
AB  - The deep inferior epigastric artery perforated rectus abdominis (DIEAP-ra) free
      flap is a modification of the classic myocutaneous DIEA free flap in which only
      fasciocutaneous tissue is harvested based on the paraumbilical perforators of the
      medial row. The aim of this retrospective study is to describe our experience
      with this reconstructive technique in head and neck surgery. Between 2004 and
      2009, 24 patients affected by oncologic maxillofacial, skull base, oral, and
      oropharyngeal defects were submitted to reconstruction with DIEAP-ra. After
      harvesting the DIEAP-ra, the longitudinally split muscular belly was sutured and
      the anterior rectus sheath closed with a nonabsorbable mattress suture without
      inlay mesh interposition. Surgical defects encompassed half of the hard palate in
      ten patients, orbit and part of the cranial vault in one, radical extended
      parotidectomy in four, subtotal glossectomy in seven, and total glossectomy in
      two cases. The only complete flap necrosis (4%) developed as a consequence of an
      orocutaneous fistula and required a second latissimus dorsi free flap. Another
      case (4%) developed a partial necrosis for oropharyngeal fistula after total
      glossectomy that healed after transposition of a pedicled myofascial pectoralis
      major. Two patients (8%) presented a minor salivary fistula that healed by
      medication alone. No major complication of the donor site was observed. DIEAP-ra
      is a valid alternative to the DIEA free flap when applied to complex
      maxillofacial or tongue major defects. Its greatest advantages are the reduced
      donor site morbidity and a more adjustable thickness of the skin paddle,
      particularly in females and obese patients.

PMID- 21866361
TI  - Electrical stimulation for neuromuscular testing and training: state-of-the art
      and unresolved issues.

PMID- 21866363
TI  - Role of arbuscular mycorrhizal symbiosis in root mineral uptake under CaCO3
      stress.
AB  - This study investigated the effects of increasing CaCO(3) concentrations (0, 5,
      10, 20 mM) on arbuscular mycorrhizal (AM) symbiosis establishment as well as on
      chicory root growth and mineral nutrient uptake in a monoxenic system. Although
      CaCO(3) treatments significantly decreased root growth and altered the symbiosis
      related development steps of the AM fungus Rhizophagus irregularis (germination,
      germination hypha elongation, root colonization rate, extraradical hyphal
      development, sporulation), the fungus was able to completely fulfill its life
      cycle. Even when root growth decreased more drastically in mycorrhizal roots than
      in non-mycorrhizal ones in the presence of high CaCO(3) levels, the AM symbiosis
      was found to be beneficial for root mineral uptake. Significant increases in P,
      N, Fe, Zn and Cu concentrations were recorded in the mycorrhizal roots. Whereas
      acid and alkaline phosphatase enzymatic activities remained constant in
      mycorrhizal roots, they were affected in non-mycorrhizal roots grown in the
      presence of CaCO(3) when compared with the control.

PMID- 21866362
TI  - Substrate use and biochemical response to a 3,211-km bicycle tour in trained
      cyclists.
AB  - The purpose of this study was to assess the physiological adaptations in
      physically fit individuals to a period of intensified training. Ten trained males
      cycled outdoors ~170 km day(-1) on 19 out of 21 days. Expired gas was collected
      on days 1 and 21 during maximal graded exercise and used for the determination of
      gross efficiency and whole body substrate use. Muscle biopsies were obtained
      before and after exercise on days 2 and 22 for the determination of mtDNA/gDNA
      ratio, gene expression, metabolic enzyme activity and glycogen use. Muscle
      glycogen before and after exercise, fat oxidation, and gross efficiency
      increased, carbohydrate oxidation decreased (p < 0.05), and VO(2max) did not
      change over the 21 days of training. Citrate synthase (CS), beta-hydroxyacyl CoA
      dehydrogenase (beta-HAD) and cytochrome c oxidase (COX) enzyme activity did not
      change with training. CS and beta-HAD mRNA did not change with acute exercise or
      training. COX (subunit IV) mRNA increased with acute exercise (p < 0.05) but did
      not change over the 21 days. PGC-1alpha mRNA increased with acute exercise, but
      did not increase to the same degree on day 22 as it did on day 2 (p < 0.05). UCP3
      mRNA decreased with training (p < 0.05). Acute exercise caused an increase in
      mitofusin2 (MFN2) mRNA (p < 0.05) and a trend for an increase in mtDNA/gDNA ratio
      (p = 0.057). However, training did not affect MFN2 mRNA or mtDNA/gDNA ratio. In
      response to 3,211 km of cycling, changes in substrate use and gross efficiency
      appear to be more profound than mitochondrial adaptations in trained individuals.

PMID- 21866365
TI  - Biogerontology: from here to where? The Lord Cohen Medal Lecture-2011.
AB  - Ageing is a progressive shrinkage of the homeodynamic space and, at the molecular
      level, it is associated with the stochastic occurrence and progressive
      accumulation of molecular damage. Imperfection of the maintenance and repair
      systems results in the failure of homeodynamics characterized by increased
      molecular heterogeneity, altered cellular functioning, reduced stress tolerance
      and reduced remodeling and adaptation, which lead to increased probability of
      diseases and eventual death. Although, several types of molecular damages have
      been shown to accumulate and increase molecular heterogeneity during ageing, its
      relevance and significance with respect to the physiology, survival and longevity
      remains to be determined. Such studies are essential for establishing biomarkers
      of health, frailty, remodeling and adaptation, and for developing effective
      methods for the prevention and reversion of age-related changes. A promising
      strategy for ageing intervention and modulation is that of strengthening the
      homeodynamics through repeated mild stress-induced hormesis by physical,
      biological and nutritional hormetins. Because a number of ethical, social, and
      personal implications emerge by the development and use of anti-ageing and life
      extending technologies, biogerontologists should incorporate these elements while
      developing their research agenda in biogerontology.

PMID- 21866364
TI  - Is there a role for measuring central aortic pressure?
AB  - Peripheral brachial blood pressure measurements by sphygmomanometry remains the
      standard for measuring and managing blood pressure. Elevated brachial blood
      pressure is a major risk for cardiovascular disease, and reduction of bracial
      blood pressure decreases target organ damage and cardiovascular events. However,
      many patients still succumb to heart disease, stroke, kidney failure, and death
      even when the brachial blood pressures appear adequately controlled. Central
      aortic pressure may be more relevant to the pathogenesis of cardiovascular
      disease, which is not always accurately represented by brachial blood pressure.
      Noninvasive applanation tonometry can now assess central aortic pressure easily
      and reliably. Emerging data suggest that central arotic pressure and related
      parameters are often better and more robust predictors of cardiovascular outcome
      than peripheral brachial blood pressures.

PMID- 21866366
TI  - Expression of MMP2 and MMP9 (gelatinases A and B) in human colon cancer cells.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral
      endopeptidases, collectively capable of degrading essentially all matrix
      components. Elevated levels of distinct MMPs are detected in tumor tissue or
      serum of patients with advanced cancer, and they are the major prognostic
      indicators in cancer. Inhibition of MMPs has been explored as a therapeutic goal
      for almost two decades. Nitric oxide (NO), a free radical plays an important role
      in signaling pathways in regulation of MMP expression. In the present study, we
      demonstrated the role of exogenous NO levels in the regulation of MMP2 and MMP9
      (gelatinases A and B) in colon cancer cell line WiDr and its inhibition with
      emodin (a naturally occurring anthraquinone).

PMID- 21866367
TI  - Outcomes of mechanically ventilated hematology patients with invasive pulmonary
      aspergillosis.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a life-threatening
      infection documented in up to 15% of hematology patients who require intensive
      care for acute respiratory failure. We report outcomes in hematology patients
      given mechanical ventilation (MV) with IPA. METHODS: Retrospective study of all
      hematology patients given MV with IPA between January 1998 and March 2011 at a
      single center. Predictors of 6-month survival or mortality were identified using
      multivariable analysis. RESULTS: We studied 67 patients including 49 (73%) with
      neutropenia, 23 (34%) with long-term steroid therapy, and 14 (21%) with
      allogeneic bone marrow transplantation. Incidence of IPA in the ICU decreased
      between 1998 and 2011, and mortality in patients receiving mechanical ventilation
      did not change. IPA was confirmed in 6 patients by autopsy and was probable in 61
      patients based on host factors, clinical and radiographic features, and either
      Aspergillus isolation (50 patients) or Aspergillus antigen detection alone (11
      patients). Concomitant bacterial infections were documented in 24 (36%) patients.
      ICU and 6-month mortality rates were 67 and 82%, respectively. Mortality was
      stable throughout the study period. Concomitant bacterial infection was
      independently associated with higher mortality [HR, 2.1 (1.2-3.8)]. Mortality was
      lower in patients given voriconazole [OR, 0.5 (0.3-0.9)]. CONCLUSION: Hospital
      mortality remains high in hematology patients requiring MV with IPA, particularly
      when concommittant infection occurred. The use of voriconazole improved survival.

PMID- 21866368
TI  - A large postoperative left ventricular hemorrhagic contusion and management by
      prolonged mechanical circulatory support: a case report.

PMID- 21866369
TI  - PEEP-induced changes in lung volume in acute respiratory distress syndrome. Two
      methods to estimate alveolar recruitment.
AB  - PURPOSE: Lung volumes, especially functional residual capacity (FRC), are
      decreased in acute respiratory distress syndrome (ARDS). Positive end-expiratory
      pressure (PEEP) contributes to increased end-expiratory lung volume (EELV) and to
      improved oxygenation, but differentiating recruitment of previously nonaerated
      lung units from distension of previously open lung units remains difficult. This
      study evaluated simple methods derived from bedside EELV measurements to assess
      PEEP-induced lung recruitment while monitoring strain. METHODS: Prospective
      multicenter study in 30 mechanically ventilated patients with ARDS in five
      university hospital ICUs. Two PEEP levels were studied, each for 45 min, and EELV
      (nitrogen washout/washin technique) was measured at both levels, with the
      difference (Delta) reflecting PEEP-induced lung volume changes. Alveolar
      recruitment was measured using pressure-volume (PV) curves. High and low
      recruiters were separated based on median recruitment at high PEEP. Minimum
      predicted increase in lung volume computed as the product of DeltaPEEP by static
      compliance was subtracted from DeltaEELV as an independent estimate of
      recruitment. Estimated and measured recruitments were compared. Strain induced by
      PEEP was also calculated from the same measurements. RESULTS: FRC was 31 +/- 11%
      of predicted. Median [25th-75th percentiles] PEEP-induced recruitment was 272
      [187-355] mL. Estimated recruitment correlated with recruited volume measured on
      PV curves (rho = 0.68), with a slope close to identity. The DeltaEELV/FRC ratio
      differentiated high from low recruiters (110 [76-135] vs. 55 [23-70]%, p =
      0.001). Strain increase due to PEEP was larger in high recruiters (p = 0.002).
      CONCLUSION: PEEP-induced recruitment and strain can be assessed at the bedside
      using EELV measurement. We describe two bedside methods for predicting low or
      high alveolar recruitment during ARDS.

PMID- 21866370
TI  - Aetiology of anorexia nervosa: from a "psychosomatic family model" to a
      neuropsychiatric disorder?
AB  - Eating disorders and, in particular, anorexia nervosa (AN) have morbidity and
      mortality rates that are among the highest of any mental disorders and are
      associated with significant functional impairment. More than 25 years ago,
      several researchers hypothesised that the prerequisite for the development of AN
      was a family process characterised by an overprotective and conflict-avoiding
      parent-child interaction. Family studies, however, suggest that AN is a complex
      genetic disorder that is likely expressed primarily by temperament and specific
      traits during childhood, including inhibition, perfectionism and harm avoidance.
      Recent studies have described an impaired flexibility and deficits in social
      cognition that are independent of body weight and the current state of the eating
      disorder, providing further evidence for a genetic component of AN. The
      physiological and psychological alterations and the increasing societal demands
      that occur during puberty may trigger onset. The starvation process itself is
      associated with severe alterations of central and peripheral metabolism,
      especially neuroendocrine and neurotransmitter changes, which are thought to
      affect the adolescent brain during the vulnerable period of neural restructuring.
      Long-standing malnutrition during adolescence and young adulthood associated with
      hormonal and neuropeptide dysfunctions may produce "biological scars" that
      maintain and accelerate the disorder and likely result in chronic mental
      disorders in adulthood as well as poor social functioning.

PMID- 21866371
TI  - Schizophrenia as a disorder of disconnectivity.
AB  - Schizophrenia is considered as a neurodevelopmental disorder with genetic and
      environmental factors playing a role. Animal models show that developmental
      hippocampal lesions are causing disconnectivity of the prefrontal cortex.
      Magnetic resonance imaging and postmortem investigations revealed deficits in the
      temporoprefrontal neuronal circuit. Decreased oligodendrocyte numbers and
      expression of oligodendrocyte genes and synaptic proteins may contribute to
      disturbances of micro- and macro-circuitry in the pathophysiology of the disease.
      Functional connectivity between cortical areas can be investigated with high
      temporal resolution using transcranial magnetic stimulation (TMS),
      electroencephalography (EEG), and magnetoencephalography (MEG). In this review,
      disconnectivity between different cortical areas in schizophrenia patients is
      described. The specificity and the neurobiological origin of these connectivity
      deficits and the relation to the symptom complex of schizophrenia and the
      glutamatergic and GABAergic system are discussed.

PMID- 21866372
TI  - Parental occupational exposure to exhausts, solvents, glues and paints, and risk
      of childhood leukemia.
AB  - PURPOSE: It is unknown whether parental occupational exposure to chemicals before
      during and after pregnancy increases the risk of acute lymphoblastic leukemia
      (ALL) in the offspring. Few studies on this topic have assessed maternal
      exposures. METHODS: In an Australian case-control study of ALL in children aged
      <15 years, parents were asked about tasks they undertook in each job using a set
      of job-specific modules (JSMs). An expert reviewed the likelihood of exposure to
      exhausts, solvents, glues, and paints. Exposure was examined in each job 2 years,
      1 year and anytime before birth of the child, and up to 1 year after birth of
      child. RESULTS: Solvent exposure was similar for case and control mothers in all
      time periods. More case mothers had moderate/high exposure to exhausts than
      control mothers anytime before the birth of the child (p = 0.010). Exposure to
      moderate or substantial levels of exhausts by mothers (OR = 1.97 95% CI 0.99
      3.90) or fathers (OR = 1.37 95% CI 1.01-1.86) before the birth increased the risk
      of ALL in their offspring. Exposure to paints, pigments, glues, and resins was
      similar in case and control parents. CONCLUSION: We found little evidence that
      parental occupational exposure to solvents, glues, and paints was associated with
      childhood ALL. There was some evidence ALL was associated with exhaust exposure.

PMID- 21866373
TI  - A case-control study of reproductive factors and renal cell carcinoma among black
      and white women in the United States.
AB  - OBJECTIVE: Renal cell carcinoma (RCC) incidence is higher among blacks than
      whites in the United States and has been associated with the frequency and timing
      of childbirth among women in some epidemiologic studies. We investigated whether
      reproductive factors are associated with RCC, overall and by race, within a
      population-based case-control study. METHODS: Between 2002 and 2007, 497 female
      cases of incident RCC (136 black, 361 white) and 546 female controls (273 black,
      273 white) within the Detroit and Chicago metropolitan areas were enrolled.
      Information on reproductive history and other factors was collected through in
      person interviews. Multivariate-adjusted odds ratios (OR) and 95% confidence
      intervals (CI) were computed using unconditional logistic regression. RESULTS:
      Reduced RCC risk was observed among women aged >=30 years at first live birth,
      relative to an age of <20 years (OR 0.5, 95% CI 0.3-0.9). This association was
      present among both white (OR 0.4, 95% CI 0.2-0.9) and, though not statistically
      significant, black women (OR 0.6, 95% CI 0.2-1.8). In analyses restricted to
      clear cell adenocarcinoma, the most common RCC histological subtype, the
      association was particularly strong (OR 0.3, 95% CI 0.2-0.8). We did not observe
      clear evidence of association with RCC for other reproductive factors.
      CONCLUSIONS: Our findings further support an association between late maternal
      age at first birth and reduced RCC risk, and suggest that the association may be
      particularly strong for clear cell adenocarcinoma.

PMID- 21866374
TI  - Content validity of patient-reported outcome measures: perspectives from a PROMIS
      meeting.
AB  - Content validity of patient-reported outcome measures (PROs) has been a focus of
      debate since the 2006 publication of the U.S. FDA Draft Guidance for Industry in
      Patient Reported Outcome Measurement. Under the auspices of the Patient Reported
      Outcomes Measurement Information System (PROMIS) initiative, a working meeting on
      content validity was convened with leading PRO measurement experts. Platform
      presentations and participant discussion highlighted key issues in the content
      validity debate, including inconsistency in the definition and evaluation of
      content validity, the need for empirical research to support methodological
      approaches to the evaluation of content validity, and concerns that continual re
      evaluation of content validity slows the pace of science and leads to the
      proliferation of study-specific PROs. We advocate an approach to the evaluation
      of content validity, which includes meticulously documented qualitative and
      advanced quantitative methods. To advance the science of content validity in
      PROs, we recommend (1) development of a consensus definition of content validity;
      (2) development of content validity guidelines that delineate the role of
      qualitative and quantitative methods and the integration of multiple
      perspectives; (3) empirical evaluation of generalizability of content validity
      across applications; and (4) use of generic measures as the foundation for PROs
      assessment.

PMID- 21866375
TI  - Pregnancy May Increase the Risk of Proximal Gastric Pouch Dilatation after LAGB
      Surgery.

PMID- 21866376
TI  - Reply to the letter of Scheimann et al.

PMID- 21866377
TI  - Laparoscopic sleeve gastrectomy feasible for bariatric revision surgery.
AB  - Bariatric revision surgery is associated with several complications that can be
      attributed to decreased quality of tissue and complexity of the surgery. A
      laparoscopic sleeve gastrectomy is a simple technique with potential advantages.
      Therefore, the results of this procedure were evaluated as a revisional option.
      Fifty-one patients underwent laparoscopic sleeve gastrectomy (LSG). Indications
      for the LSG were insufficient weight loss (34 patients, group 1) or vomiting (17
      patients, group 2) following a laparoscopic adjustable gastric banding (LAGB) or
      vertical banded gastroplasty (VBG). Patient and procedure characteristics as well
      as outcome were collected prospectively. From October 2006 to June 2010, 51
      patients with a failed prior bariatic procedure (VBG or LAGB) were converted to
      (L)SG. The conversion rate was zero. The median procedure time was 99 min (range
      54-221) and hospital stay was 3 days (range 2-38). There was no mortality after
      30 days. Complications included bleeding (six) and leakage of the staple line
      (seven). Mean follow-up was 13.8 (2-46) months. LSG as revision surgery for
      insufficient weight loss resulted in extra weight loss of 52.7%, and the overall
      extra weight loss was 49.3%. When LSG was performed because of vomiting, 82% was
      able to eat solid food at follow-up. Of the 65 pre-existent co-morbidities, 21
      were resolved and 18 improved. LSG as a revision procedure is feasible. An
      additional weight loss and further resolution of co-morbidity seem achievable,
      however, at the cost of a high number of complications. Therefore, revision
      bariatric surgery should be limited to expert tertiary bariatric centers.

PMID- 21866379
TI  - Agrometeorological parameters for prediction of the maturation period of Arabica
      coffee cultivars.
AB  - The objective of this study was to determine the harvest period of coffee fruits
      based on the relationship between agrometeorological parameters and sucrose
      accumulation in the seeds. Over the crop years 2004/2005 and 2006/2007, from 150
      days after flowering (DAF) onwards, samples of 50 fruits of cultivars Mundo Novo
      IAC 376-4, Obata IAC 1669-20 and Catuai Vermelho IAC 144 were collected from
      coffee trees located in Campinas, Brazil. The endosperm of the fruits was freeze
      dried, ground and analyzed for sucrose content by high-performance liquid
      chromatography. A weather station provided data to calculate the accumulated
      growing degree-day (GDD) units, and the reference (ET(o)) and actual (ET(r))
      evapotranspiration rates. The results showed that the highest rates of sucrose
      accumulation occurred at the transition from the cane-green to the cherry
      phenological stage. Models for the estimation of sucrose content during
      maturation based on meteorological variables exhibited similar or better
      performance than the DAF variable, with better results for the variables GDD and
      ET(o). The Mundo Novo cultivar reached the highest sucrose level in the endosperm
      after 2,790 GDD, while cultivar Catuai attained its maximum sucrose concentration
      after the accumulated evapotranspiration rate has reached a value of 870 mm. As
      for cultivar Obata, the maximum sucrose concentration was predicted with the same
      degree of accuracy using any of the parameters investigated. For the Obata
      cultivar, the values of the variables calculated for the maximum sucrose
      concentration to be reached were 249 DAF, 3,090 GDD, 1,020 ET(o) and 900 ET(r).

PMID- 21866378
TI  - Thirty-day mortality after bariatric surgery: independently adjudicated causes of
      death in the longitudinal assessment of bariatric surgery.
AB  - BACKGROUND: Mortality following bariatric surgery is a rare event in contemporary
      series, making it difficult for any single center to draw meaningful conclusions
      as to cause of death. Nevertheless, much of the published mortality data come
      from single-center case series and reviews of administrative databases. These
      sources tend to produce lower mortality estimates than those obtained from
      controlled clinical trials. Furthermore, information about the causes of death
      and how they were determined is not always available. The aim of the present
      report is to describe in detail all deaths occurring within 30 days of surgery in
      the Longitudinal Assessment of Bariatric Surgery (LABS). METHODS: LABS is a ten
      center observational cohort study of bariatric surgical outcomes. Data were
      collected prospectively for bariatric surgeries performed between March 2005 and
      April 2009. All deaths occurring within 30-days of surgery were identified, and
      cause of death assigned by an independent Adjudication Subcommittee, blinded to
      operating surgeon and site. RESULTS: Six thousand one hundred eighteen patients
      underwent primary bariatric surgery. Eighteen deaths (0.3%) occurred within 30
      days of surgery. The most common cause of death was sepsis (33% of deaths),
      followed by cardiac causes (28%), and pulmonary embolism (17%). For one patient
      cause of death could not be determined despite examination of all available
      information. CONCLUSIONS: This study confirms the low 30-day mortality rate
      following bariatric surgery. The recognized complications of anastomotic leak,
      cardiac events, and pulmonary emboli accounted for the majority of 30-day deaths.

PMID- 21866380
TI  - Growing degree-days for the 'Niagara Rosada' grapevine pruned in different
      seasons.
AB  - Plant growth and development are proportional to biological time, or the thermal
      time of the species, which can be defined as the integral of the temperature over
      time between the lower and upper temperature developmental thresholds. The
      objective of this study was to investigate the efficiency of the growing degree
      day (GDD) approach for vines of the 'Niagara Rosada' cultivar pruned in winter
      and summer seasons, and physiological phases (mobilisation and reserve
      accumulation) in a humid subtropical region. The experiment was carried out on 13
      year-old plants in Piracicaba, Sao Paulo State-Brazil, evaluating 24 production
      cycles, 12 from the winter pruning, and 12 from the summer pruning. The
      statistical design was comprised of randomised blocks, using the pruning dates as
      treatment: 20 July, 4 August, 19 August, and 3 September (winter); 1 February, 15
      February, 2 March, and 16 March (summer). Comparison of the mean values of GDD
      among pruning dates was evaluated by the Tukey test, and comparison between
      pruning seasons was made by the F test for orthogonal contrasts, both at the 5%
      probability level. The results showed good agreement between the values of GDD
      required to complete the cycle from the winter pruning until harvest when
      compared with other studies performed with the same cultivar grown in the
      Southern and Southeastern regions of Brazil. However, there was a consistent
      statistical difference between GDD computed for winter and summer pruning, which
      allowed us to conclude that this bio-meteorological index is not sufficient to
      distinguish vines pruned in different seasons and physiological phases applied in
      humid subtropical climates.

PMID- 21866381
TI  - Ambulatory blood pressure monitoring in children: imperfect yet essential.
AB  - There has been increasing emphasis on hypertension and early cardiovascular
      disease in the pediatric age group over the past decade as a result of various
      factors, including the obesity epidemic and publication of new clinical
      guidelines. A key component of identifying children and adolescents with definite
      or potential hypertension is proper blood pressure (BP) measurement. While
      ambulatory blood pressure monitoring (ABPM) offers the potential for improved
      detection of youths at increased cardiovascular risk, it has not been widely
      adopted. This commentary highlights the crucial role of ABPM in the context of
      current trends, while at the same time identifying the current barriers to more
      widespread application of this technique. Chief among these is the lack of a
      robust, universally applicable database of pediatric ABPM normative values. Even
      in the absence of ideal normative data, ABPM can and should be widely applied,
      and a potential algorithm for such an approach is presented.

PMID- 21866382
TI  - Overweight, insulin resistance and blood pressure (parameters of the metabolic
      syndrome) in uric acid urolithiasis.
AB  - Overweight, arterial hypertension and disturbances of the carbohydrate metabolism
      are important parameters of the metabolic syndrome (MS). The most important
      factor regarding renal pathophysiology is insulin resistance resulting in
      alterations of urine acidification and low urine pH. Since low urine pH is the
      main risk factor for uric acid urolithiasis (UAU), UAU may be regarded as a renal
      manifestation of the MS. So far, there are only few data on the prevalence of
      parameters of the MS in UAU patients especially with regard to the severity of
      the disease and recurrence rate, respectively. The objective of this study was to
      know more about the prevalence of different parameters of the MS and their
      importance for the natural history of this type of renal stone disease using a
      total number of 167 consecutive patients with pure UA stones. Stone analysis was
      performed by polarization microscopy and X-ray diffraction. The following
      parameters were measured: age, sex, systolic and diastolic arterial blood
      pressure (RRs and RRd), number of stone episodes, diabetes mellitus (DM); serum:
      creatinine, calcium, sodium, potassium, uric acid, glucose; urine: pH-profiles,
      citrate, calcium, uric acid, ammonia, urea, and creatinine. The following results
      were obtained (means +/- standard deviations): age 61 +/- 13 years, BMI 30 +/- 6
      kg/m(2), BP 147/84 +/- 22/13 mmHg, number of stone episodes 1.8 +/- 1.2, DM 32%;
      serum: creatinine 1.3 +/- 0.6 mg/dl, glucose 136 +/- 52 mg/dl, UA 6.3 +/- 1.8
      mg/dl, calcium 2.4 +/- 1.3 mmol/l, sodium 134 +/- 18 mmol/l, potassium 4.1 +/-
      0.4 mmol/l; urine: pH 5.87 +/- 0.27, volume 2.4 +/- 1.1 l/d, calcium 3.5 +/- 2.5
      mmol/d, UA 3.9 +/- 2.4 mmol/d, citrate 1.3 +/- 1.1 mmol/d, ammonia 41 +/- 26
      mmol/d, urea 390 +/- 176 mmol/d. A significant positive correlation could be
      found for BMI and urea excretion, BMI correlated negatively with RRs and RRd.
      There was no significant correlation between BMI, urine pH, citrate, ammonia and
      UA in serum and urine. Undue acidity and hyperuricosuria were found in two-thirds
      of the UAU patients, increased urea excretion and decreased excretion of ammonia
      in less than 25%, Hyperuricemia in 37%. There was no significant correlation
      between the number of stone episodes and any other parameter studied. Overweight,
      arterial hypertension and DM as parameters of the MS are frequent in many
      patients with UAU. However, these parameters do explain the pathogenesis in two
      thirds of the patients. The severity of the disease and the recurrence are not
      influenced by the presence of these metabolic parameters. Therefore, MS is no
      prognostic factor in UAU.

PMID- 21866383
TI  - Role of angiogenetic factors in cardiac valve homeostasis and disease.
AB  - The aging of populations worldwide and the habitual consumption of food high in
      calories and cholesterol have led to recent increases in morbidity from calcific
      aortic valve disease. At the same time, rupture of the chordae tendineae cordis,
      which is a component of the mitral valve complex, is one of the major causes of
      mitral regurgitation. Surgery is the basis of treatment for these diseases, and
      little is known about their causes and mechanisms. A balance of angiogenetic and
      angioinhibitory factors is crucial for normal development and homeostasis of many
      organs. Although the heart is a vascular-rich organ, most of the cardiac valve
      complex is avascular like cartilage and tendons. Our studies have focused on the
      role of angiogenetic factors expressed in the cartilage and tendons in cardiac
      valve homeostasis. Recently, we found that chondromodulin-I, tenomodulin, and
      periostin play essential roles in degeneration and/or rupture of the cardiac
      valve complex by controlling angiogenesis and matrix metalloproteinase
      production. Here, we review the mechanistic insights provided by these studies
      and the proposed roles of angiogenetic factors in cardiac valve homeostasis and
      disease.

PMID- 21866384
TI  - Effects on arrhythmogenesis and arrhythmic threshold of injection of autologous
      fibroblasts into myocardial infarcts in adult pigs.
AB  - Myocardial dysfunction is strongly associated with a higher rate of ventricular
      arrhythmia and sudden death. Clinical studies indicate that intramyocardial
      injection of autologous cells to augment contractile function may modify the
      arrhythmogenic substrate. The aim of this study was to assess the effects of
      epicardial injections of autologous dermal fibroblasts in infarcted pigs on the
      incidence of spontaneous and induced ventricular tachycardia. In eight pigs,
      myocardial infarction was induced, and the skin was excised for fibroblast
      isolation, culture, and labeling with bromodeoxyuridine (BrdU). After 3 weeks,
      animals received epicardial injection of the autologous fibroblasts (n = 4) or
      saline (n = 4) across the scarred and border zone regions, with continuous ECG
      monitoring for the following 4 weeks. Electrophysiologic study with programmed
      stimulation was performed before injections and at sacrifice, and histological
      analysis was performed. ECG monitoring showed that the fibroblast group had a
      lower total number of ectopic ventricular complexes per day when compared to the
      control group (58 +/- 119 versus 478 +/- 1,308 respectively; p = 0.013) and fewer
      episodes of non-sustained ventricular arrhythmia per day (0 episodes versus 31 +/
      148 respectively; p = 0.001). Inducibility during programmed ventricular
      stimulation was no different between the groups. Histological analysis disclosed
      the presence of viable BrdU-labeled cells in injected areas. This study showed
      that fibroblasts can be safely transplanted in an infarcted heart and survive for
      at least 4 weeks. Fibroblast injection did not increase the inducibility of
      ventricular tachycardia, and reduced the incidence of spontaneous ventricular
      tachycardia.

PMID- 21866385
TI  - Mitral valve disease in Marfan syndrome and related disorders.
AB  - Marfan syndrome (MFS) is a systemic disorder of the connective tissue with
      pleiotropic manifestations due to heterozygous FBN1 mutations and consequent
      upregulation of TGFbeta signaling in affected tissues. Myxomatous thickening and
      elongation of the mitral valve (MV) leaflets commonly occur in this condition.
      Investigation of murine models of this disease has led to improved understanding
      of the mechanisms that underlie many of the phenotypic features of MFS, including
      MV disease. Loeys-Dietz syndrome (LDS) is a related disorder due to heterozygous
      mutations in the genes encoding subunits of the TGFbeta receptor, and it may also
      involve the MV leaflets with similar elongation and thickening of the MV
      leaflets. Although the genetic basis and pathogenesis of nonsyndromic MV prolapse
      has been elusive to date, insights derived from monogenic disorders like MFS and
      LDS can be informative with regard to novel gene discovery and investigation into
      the pathogenesis of MV disease. This manuscript will review the prevalence of MV
      disease in MFS, its pathogenic basis as determined in mice with Fbn1 mutations,
      and ongoing studies that seek to better understand MV disease in the context of
      fibrillin-1 deficiency or excessive TGFbeta signaling.

PMID- 21866386
TI  - Automatic computation of electrode trajectories for Deep Brain Stimulation: a
      hybrid symbolic and numerical approach.
AB  - PURPOSE: The optimal electrode trajectory is needed to assist surgeons in
      planning Deep Brain Stimulation (DBS). A method for image-based trajectory
      planning was developed and tested. METHODS: Rules governing the DBS surgical
      procedure were defined with geometric constraints. A formal geometric solver
      using multimodal brain images and a template built from 15 brain MRI scans were
      used to identify a space of possible solutions and select the optimal one. For
      validation, a retrospective study of 30 DBS electrode implantations from 18
      patients was performed. A trajectory was computed in each case and compared with
      the trajectories of the electrodes that were actually implanted. RESULTS:
      Computed trajectories had an average difference of 6.45 degrees  compared with
      reference trajectories and achieved a better overall score based on satisfaction
      of geometric constraints. Trajectories were computed in 2 min for each case.
      CONCLUSION: A rule-based solver using pre-operative MR brain images can
      automatically compute relevant and accurate patient-specific DBS electrode
      trajectories.

PMID- 21866387
TI  - [Certification of vascular centers. Influence on quality and healthcare
      structures].
AB  - Diagnosis and therapy of vascular diseases are increasingly being performed
      following a multimodal, interdisciplinary and less invasive approach. The
      introduction of specialized, organ-related centers is a logical consequence in
      view of a better treatment quality and a more effective use of resources. The
      German societies of radiology, vascular surgery and angiology jointly developed a
      process of certification, which has been successfully applied to more than 100
      units in Germany. In this article the terms and results of the process are
      described and possible effects on the quality and structures of the healthcare
      system are discussed.

PMID- 21866388
TI  - [Volar locking plating for distal radial fractures. Is osteoporosis associated
      with poorer functional results and higher complications rates?].
AB  - BACKGROUND: The purpose of this prospective study was to compare the functional
      and radiological results and complication rates after locking plate
      osteosynthesis of unstable distal radial fractures in elderly patients as a
      function of the bone mineral density (BMD). The hypothesis that reduced BMD is
      accompanied by poorer function and a higher rate of complications was
      investigated. PATIENTS AND METHODS: A total of 65 consecutive patients with
      unstable distal radial fractures, AO 23-A2 (n=1), -A3 (n=29), -C1 (n=2), -C2
      (n=28) and -C3 (n=5) were included with a mean age of 69 years (range, 52-86
      years). Standardized clinical and radiological follow-up was performed 6 weeks, 3
      and 12 months postoperatively. All patients underwent dual x-ray absorptiometry
      of the contralateral distal radius within 6 weeks postoperatively and 3 groups
      could be differentiated: group I (n=27) osteoporosis, group II (n=27) osteopenia
      and group III (n=11) normal BMD. Data on the DASH and QAL scores as well as the
      range of motion, grip strength and radiological parameters were collected.
      According to the BMD a detailed analysis of complications was performed. RESULTS:
      Exemplary the 12 months results of DASH and the range of motion are shown here:
      the DASH 12 months postoperatively was DASH(total)=6 (0-64) P, DASH(group I)=7 (0
      32.5) P, DASH(group II)=11 (1-63) P, DASH(group III)=2 (0-23) P, no significance.
      The range of motion increased significantly in all 3 groups (except pronation in
      groups I and III) from 6 weeks to 3 and 12 months postoperatively and 12 months
      postoperatively showed means for dorsal extension 55 degrees  (25-75), palmar
      flexion 55 degrees  (35-75), ulnar abduction 35 degrees  (20-45), radial
      abduction 20 degrees  (5-40), supination 90 degrees  (60-90) and pronation 85
      degrees  (65-90) in the total sample. The comparison of DASH and range of motion
      was not significantly different at each time of follow-up between all 3 groups. A
      group-specific analysis of implant and BMD dependent complications showed 2/27
      (7%) secondary intra-articular screw perforations in group I, 1/27 (4%) in group
      II and 0/11 in group III. CONCLUSION: The hypothesis that a reduced BMD is
      accompanied by a poorer function and a higher rate of complications was refuted.
      Analysis of complications showed a trend to more BMD-dependent complications in
      the osteoporosis group.

PMID- 21866389
TI  - [Operative treatment of chronic mesenteric ischemia].
AB  - Chronic ischemic lesions of the splanchnic organs are often underestimated and
      underdiagnosed. The etiology, therapy and prognosis of acute mesenteric ischemia
      can be distinguished from chronic splanchnic ischemia. Progression of underlying
      atherosclerosis and the polymorbidity of the aging population results in an
      increased prevalence of chronic mesenteric ischemia, and occlusions of splanchnic
      arteries are diagnosed more frequently. Due to excellent collateralization,
      diffuse stenotic processes may remain asymptomatic for a long time. Computed
      tomography angiography with 3D reconstruction is the preferred diagnostic tool,
      while diagnostic angiography is more often utilized in combination with
      endovascular treatment (catheter-derived infusion therapy, lysis, percutaneous
      transluminal angioplasty, stent). Duplex sonography reveals relevant insights
      into the hemodynamic severity of the lesion. However, the diagnostic accuracy of
      Duplex sonograpy is often restricted due to bowel gas and operator dependency.In
      this article the operative treatment of chronic intestinal ischemia is discussed
      and a classification for treatment stratification is proposed.

PMID- 21866391
TI  - II. In vitro evidence that (-)-OSU6162 and (+)-OSU6162 produce their behavioral
      effects through 5-HT2A serotonin and D2 dopamine receptors.
AB  - (-)-OSU6162 has promise for treating Parkinson's disease, Huntington's disease
      and schizophrenia. Behavioral tests evaluating the locomotor effects of (-) and
      (+)-OSU6162 on 'low activity' animals (reserpinized mice and habituated rats) and
      'high activity' animals (drug naive mice and non-habituated rats) revealed that
      both enantiomers of OSU6162 had dual effects on behavior, stimulating locomotor
      activity in 'low activity' animals and inhibiting locomotor activity in 'high
      activity' animals. To elucidate a plausible mechanism of action for their
      behavioral effects, we evaluated the intrinsic actions of (-)- and (+)-OSU6162,
      and a collection of other antipsychotic and antiparkinsonian agents at 5-HT2A and
      D2 receptors in functional assays with various degrees of receptor reserve,
      including cellular proliferation, phosphatidyl inositol hydrolysis, GTPgammaS and
      beta-arrestin recruitment assays. We also tested for possible allosteric actions
      of (-)-OSU6162 at D2 receptors. Both enantiomers of OSU6162 were medium intrinsic
      activity partial agonists at 5-HT2A receptors and low intrinsic activity partial
      agonists at D2 receptors. (+)-OSU6162 had higher efficacy at 5-HT2A receptors,
      which correlated with its greater stimulatory activity in vivo, but (-)-OSU6162
      had higher potency at D2 receptors, which correlated with its greater inhibitory
      activity in vivo. (-)-OSU6162 did not display any convincing allosteric
      properties. Both (+)- and (-)-OSU6162 were significantly less active at 27 other
      monoaminergic receptors and reuptake transporters tested suggesting that D2 and 5
      HT2A receptors play crucial roles in mediating their behavioral effects.
      Compounds with balanced effects on these two receptor systems may offer promise
      for treating neuropsychiatric diseases.

PMID- 21866390
TI  - Hypomethylating drugs efficiently decrease cytosine methylation in telomeric DNA
      and activate telomerase without affecting telomere lengths in tobacco cells.
AB  - Telomere homeostasis is regulated at multiple levels, including the local
      chromatin structure of telomeres and subtelomeres. Recent reports demonstrated
      that a decrease in repressive chromatin marks, such as levels of cytosine
      methylation in subtelomeric regions, results in telomere elongation in mouse
      cells. Here we show that a considerable fraction of cytosines is methylated not
      only in subtelomeric, but also in telomeric DNA of tobacco BY-2 cells. Drug
      induced hypomethylation (demonstrated at subtelomeric, telomeric, and global DNA
      levels) results in activation of telomerase. However, in contrast to mouse cells,
      the decrease in 5-methylcytosine levels and upregulation of telomerase do not
      result in any changes of telomere lengths. These results demonstrate the
      involvement of epigenetic mechanisms in the multilevel process of regulation of
      telomerase activity in plant cells and, at the same time, they indicate that
      changes in telomerase activity can be overridden by other factors governing
      telomere length stability.

PMID- 21866393
TI  - CDC's Prevention Research Centers Program: translating research into action with
      communities.

PMID- 21866392
TI  - A retrieval algorithm to evaluate the Photosystem I and Photosystem II spectral
      contributions to leaf chlorophyll fluorescence at physiological temperatures.
AB  - A new computational procedure to resolve the contribution of Photosystem I (PSI)
      and Photosystem II (PSII) to the leaf chlorophyll fluorescence emission spectra
      at room temperature has been developed. It is based on the Principal Component
      Analysis (PCA) of the leaf fluorescence emission spectra measured during the OI
      photochemical phase of fluorescence induction kinetics. During this phase, we can
      assume that only two spectral components are present, one of which is constant
      (PSI) and the other variable in intensity (PSII). Application of the PCA method
      to the measured fluorescence emission spectra of Ficus benjamina L. evidences
      that the temporal variation in the spectra can be ascribed to a single spectral
      component (the first principal component extracted by PCA), which can be
      considered to be a good approximation of the PSII fluorescence emission spectrum.
      The PSI fluorescence emission spectrum was deduced by difference between measured
      spectra and the first principal component. A single-band spectrum for the PSI
      fluorescence emission, peaked at about 735 nm, and a 2-band spectrum with maxima
      at 685 and 740 nm for the PSII were obtained. A linear combination of only these
      two spectral shapes produced a good fit for any measured emission spectrum of the
      leaf under investigation and can be used to obtain the fluorescence emission
      contributions of photosystems under different conditions. With the use of our
      approach, the dynamics of energy distribution between the two photosystems, such
      as state transition, can be monitored in vivo, directly at physiological
      temperatures. Separation of the PSI and PSII emission components can improve the
      understanding of the fluorescence signal changes induced by environmental factors
      or stress conditions on plants.

PMID- 21866394
TI  - Increasing the activity of copper(II) complexes against Leishmania through
      lipophilicity and pro-oxidant ability.
AB  - Copper complexes with fluorinated beta-diketones were synthesized and
      characterized in terms of lipophilicity and peroxide-assisted oxidation of
      dihydrorhodamine as an indicator of redox activity. The biological activity of
      the complexes was tested against promastigotes of Leishmania amazonensis.
      Inhibition of trypanosomatid-specific trypanothione reductase was also tested. It
      was found that the highly lipophilic and redox-active
      bis(trifluoroacetylacetonate) derivative had increased toxicity towards
      promastigotes. These results indicate that it is possible to modulate the
      activity of metallodrugs based on redox-active metals through the appropriate
      choice of lipophilic chelators in order to design new antileishmanials. Further
      work will be necessary to improve selectivity of these compounds against the
      parasite.

PMID- 21866395
TI  - A simplified recipe for assigning amide NMR signals using combinatorial 14N amino
      acid inverse-labeling.
AB  - Assignment of backbone amide proton resonances is one of the most time-consuming
      stages of any protein NMR study when the protein samples behave non-ideally. A
      robust and convenient NMR procedure for analyzing spectra of marginal-to-low
      quality is helpful for high-throughput structure determination. The 14N selective
      and inverse-labeling method is a candidate solution. Here, we present a
      simplified protocol for assigning protein backbone amide NMR signals. When 14N
      inversely labeled residues are present in a protein, their backbone NH cross
      peaks vanish from the protein's 1H-(15)N HSQC spectrum, and thus, their chemical
      shifts can be readily identified by a process of elimination. Some metabolically
      related amino acids, for example, Ile, Leu, and Val, cannot be individually
      incorporated but can be inversely labeled together. We optimized and simplified
      the protocol and M9-based medium formula for the 14N selective- and inverse
      labeling method without any additives. Our approach should be cost-effective,
      because the method could be additively applied stepwise, even when the proteins
      of interest were found to be non-ideal.

PMID- 21866396
TI  - C3 peptide promotes axonal regeneration and functional motor recovery after
      peripheral nerve injury.
AB  - Peripheral nerve injuries are frequently seen in trauma patients and due to
      delayed nerve repair, lifelong disabilities often follow this type of injury.
      Innovative therapies are needed to facilitate and expedite peripheral nerve
      regeneration. The purpose of this study was to determine the effects of a 1-time
      topical application of a 26-amino-acid fragment (C3(156-181)), derived from the
      Clostridium botulinum C3-exoenzyme, on peripheral nerve regeneration in 2 models
      of nerve injury and repair in adult rats. After sciatic nerve crush, different
      dosages of C3(156-181) dissolved in buffer or reference solutions (nerve growth
      factor or C3(bot)-wild-type protein) or vehicle-only were injected through an
      epineurial opening into the lesion sites. After 10-mm nerve autotransplantation,
      either 8.0 nmol/kg C3(156-181) or vehicle were injected into the proximal and
      distal suture sites. For a period of 3 to 10 postoperative weeks, C3(156-181)
      treated animals showed a faster motor recovery than control animals. After crush
      injury, axonal outgrowth and elongation were activated and consequently resulted
      in faster motor recovery. The nerve autotransplantation model further elucidated
      that C3(156-181) treatment accounts for better axonal elongation into motor
      targets and reduced axonal sprouting, which are followed by enhanced axonal
      maturation and better axonal functionality. The effects of C3(156-181) are likely
      caused by a nonenzymatic down-regulation of active RhoA. Our results indicate the
      potential of C3(156-181) as a therapeutic agent for the topical treatment of
      peripheral nerve repair sites.

PMID- 21866397
TI  - Which factors predict glycemic control in children diagnosed with type 1 diabetes
      before 6.5 years of age?
AB  - Predictors of long-term glycemic control and growth patterns in children
      diagnosed with type 1 diabetes (T1D) before 6.5 years of age were evaluated. One
      hundred seventy-three children (84 boys) with a mean diabetes duration of 4.9 +/-
      2.8 years participated in this observational study. Medical charts were reviewed
      for background, disease- and treatment-related parameters, and growth parameters.
      Study endpoints were HbA1c value, rates of severe hypoglycemia and diabetic
      ketoacidosis events, and growth patterns. Mean HbA1c for the total duration of
      diabetes (HbA1c-TDD) was 7.9 +/- 0.8%. Comparison of the study variables between
      patients with HbA1c-TDD <7.5% (n = 53) or >=7.5% yielded a significantly shorter
      duration of diabetes (P = 0.01) and lower rate of diabetic ketoacidosis (P =
      0.02) in those with HbA1C-TDD <7.5%, without differences between these groups in
      age at diabetes onset, insulin regimens, daily glucose measurements, and rate of
      severe hypoglycemia. Factors significantly predicting achievement of the mean
      target HbA1c-TDD <7.5% were lower HbA1c at 0.5 years and 1 year after diabetes
      diagnosis (P = 0.002 and P < 0.001, respectively). Patients followed for at least
      5 years (n = 48) showed a significant decrease in height-SDS (P < 0.001) and a
      significant increase in weight-SDS (P = 0.004) from diabetes diagnosis to the
      last follow-up visit, without a significant change in weight-SDS from 0.5 years
      after diagnosis to the last follow-up visit. Our results suggest that in patients
      with T1D diagnosed during the preschool-age, mean HbA1c level in the first year
      is a strong predictor of achieving target HbA1c level in the subsequent years,
      regardless the type of insulin regimen. This "metabolic tracking" emphasizes the
      importance of achieving early optimal control even in younger children.

PMID- 21866398
TI  - CD40 C/T(-1) and CTLA-4 A/G(49) SNPs are associated with autoimmune thyroid
      diseases in the Chinese population.
AB  - This study was to investigate whether the common polymorphisms of CD40 and CTLA4
      genes confer susceptibility to AITD in the Chinese population. A set of unrelated
      subjects including 303 GD patients, 208 HT patients, and 215 matched healthy
      controls were recruited. SNPs were genotyped by the method of PCR-RFLP. (1) As
      for CD40 C/T(-1) SNP, only a significant difference was found in allele
      frequencies between GD and control groups (P = 0.033). (2) On the part of CTLA-4
      A/G(49) SNP, significant differences were found in genotype and allele
      frequencies between GD and control groups (P = 7.0 * 10(-5) and P = 0.002,
      respectively), and similar results were found between HT and control groups (P =
      0.015 and P = 0.003, respectively). (3) The logistic regression analysis showed
      there was no interaction between CD40 and CTLA4 genotypes (P = 0.262). These
      results indicate that both CTLA-4 A/G(49) and CD40 C/T(-1) SNPs are associated
      with genetic susceptibility of GD, and CTLA-4 A/G(49) is also associated with HT.

PMID- 21866399
TI  - Current status of hyphenated mass spectrometry in studies of the metabolism of
      drugs of abuse, including doping agents.
AB  - This paper reviews scientific contributions on the identification and/or
      quantification of metabolites of drugs of abuse in in vitro assays or various
      body samples using hyphenated mass spectrometry. Gas chromatography-mass
      spectrometry (GC-MS) as well as liquid chromatography-mass spectrometry (LC-MS)
      approaches are considered and discussed if they have been reported in the last
      five years and are relevant to clinical and forensic toxicology or doping
      control. Workup and artifact formation are discussed, and typical examples of
      studies of the metabolism of designer drugs, doping agents, herbal drugs, and
      synthetic cannabinoids are provided. Procedures for quantifying metabolites in
      body samples for pharmacokinetic studies or in enzyme incubations for enzyme
      kinetic studies are also reviewed. In conclusion, the reviewed papers showed that
      both GC-MS and LC-MS still have important roles to play in research into the
      metabolism of drugs of abuse, including doping agents.

PMID- 21866400
TI  - Multi-capillary column-ion mobility spectrometry: a potential screening system to
      differentiate virgin olive oils.
AB  - The potential of a headspace device coupled to multi-capillary column-ion
      mobility spectrometry has been studied as a screening system to differentiate
      virgin olive oils ("lampante," "virgin," and "extra virgin" olive oil). The last
      two types are virgin olive oil samples of very similar characteristics, which
      were very difficult to distinguish with the existing analytical method. The
      procedure involves the direct introduction of the virgin olive oil sample into a
      vial, headspace generation, and automatic injection of the volatiles into a gas
      chromatograph-ion mobility spectrometer. The data obtained after the analysis by
      duplicate of 98 samples of three different categories of virgin olive oils, were
      preprocessed and submitted to a detailed chemometric treatment to classify the
      virgin olive oil samples according to their sensory quality. The same virgin
      olive oil samples were also analyzed by an expert's panel to establish their
      category and use these data as reference values to check the potential of this
      new screening system. This comparison confirms the potential of the results
      presented here. The model was able to classify 97% of virgin olive oil samples in
      their corresponding group. Finally, the chemometric method was validated
      obtaining a percentage of prediction of 87%. These results provide promising
      perspectives for the use of ion mobility spectrometry to differentiate virgin
      olive oil samples according to their quality instead of using the classical
      analytical procedure.

PMID- 21866402
TI  - Laser-induced fluorescence and FT-Raman spectroscopy for characterizing patinas
      on stone substrates.
AB  - This article reports on a compositional investigation of stone patinas: thin
      colored layers applied for protective and/or aesthetic purposes on architectural
      or sculptural substrates of cultural heritage. The analysis and classification of
      patinas provide important information of historic and artistic interest, as their
      composition reflects local practices, the availabilities of different materials,
      and the development of technological knowledge during specific historical
      periods. Model patinas fabricated according to traditional procedures and applied
      onto limestone, and a historic patina sample from the main facade of the San Blas
      Monastery in Lerma (a village in the province of Burgos, Spain), were analyzed by
      laser-induced fluorescence and Fourier transform Raman spectroscopy. The results
      obtained demonstrate the ability of these two analytical techniques to identify
      the key components of each formulation and those of the reaction products which
      result from the chemical and mineralogical transformations that occur during
      aging, as well as to provide information that can aid the classification of
      different types of patinas.

PMID- 21866401
TI  - Development of an LC-MS/MS method for the analysis of serotonin and related
      compounds in urine and the identification of a potential biomarker for attention
      deficit hyperactivity/hyperkinetic disorder.
AB  - Serotonin is a major neurotransmitter and affects various functions both in the
      brain and in the rest of the body. It has been demonstrated that altered
      serotinergic function is implicated in various psychiatric disorders including
      depression and schizophrenia. Serotonin has also been implicated along with
      dopamine in attention deficit-hyperkinetic disorder (AD-HKD). This study provides
      a versatile validated method for the analysis of serotonin, hydroxyindole acetic
      acid and dopamine in urine using LC-MS/MS. This method was then used to quantify
      these analytes in a test group of 17 children diagnosed with severe AD-HKD. This
      group was compared to a matched control group to investigate the possibility that
      one of these compounds may be a potential biomarker for this condition. The
      developed method provided good linear calibration curves for the multiplex assay
      of analytes in urine (0.05-3.27 nmol/L; R(2) >= 0.9977). Acceptable inter-day
      repeatability was achieved for all analytes with RSD values (n = 9) ranging from
      1.1% to 9.3% over a concentration range of 0.11-3.27 MUmol/L in urine. Excellent
      limits of detection (LOD) and limits of quantitation (LOQ) were achieved with
      LODs of 8.8-18.2 nmol/L and the LOQs of 29.4-55.7 nmol/L for analytes in urine.
      Recoveries were in the ranges of 98-104%, 100-106% and 91-107% for serotonin, 5
      HIAA and dopamine, respectively. An appropriate sample clean-up procedure for
      urine was developed to ensure efficient recovery and reproducibility on analysis.
      Evaluation of matrix effects was also carried out and the influence of ion
      suppression on analytical results reported. Confirmatory analysis was carried out
      on a linear trap quadrupole-Orbitrap mass spectrometer to obtain high mass
      accuracy data of the target analytes in the clinical samples.

PMID- 21866403
TI  - Functionalized gold nanoparticles for ultrasensitive DNA detection.
AB  - A major challenge in the area of DNA detection is the development of rapid
      methods that do not require polymerase chain reaction (PCR) amplification of the
      genetic sample. The PCR amplification step increases the cost of the assay, the
      complexity of the detection, and the quantity of DNA required for the assay. In
      this context, methods that are able to perform DNA analyses with ultrasensitivity
      have recently been investigated with the aim of developing new PCR-free detection
      protocols. Functionalized gold nanoparticles have played a central role in the
      development of such methods. Here, possibilities offered by functionalized gold
      nanoparticle in the ultrasensitive detection of DNA are discussed. The different
      functionalization protocols available for gold nanoparticles and the principal
      DNA detection methods that are able to detect DNA at the femtomolar to attomolar
      level are presented.

PMID- 21866404
TI  - Layer-by-layer construction of protein architectures through avidin-biotin and
      lectin-sugar interactions for biosensor applications.
AB  - In this review, the preparation and properties of protein architectures
      constructed by layer-by-layer (LbL) deposition through avidin-biotin and
      concanavalin A (Con A)-sugar interactions are discussed in relation to their use
      for optical and electrochemical biosensors. LbL films can be constructed through
      the alternate deposition of avidin and biotin-labeled enzymes on the surfaces of
      optical probes and electrodes. The enzymes retain their catalytic activity,
      resulting in the formation of optical and electrochemical biosensors.
      Alternatively, Con A can be used to construct enzyme-containing LbL films and
      microcapsules using sugar-labeled enzymes. Some enzymes such as glucose oxidase
      and horseradish peroxidase can be used for this purpose without labeling with
      sugar, because these enzymes contain intrinsic hydrocarbon chains on their
      molecular surfaces. The Con A/enzyme LbL architectures were successfully used to
      develop biosensors sensitive to specific substrates of the enzyme. In addition,
      Con A-based films can be used for the optical and electrochemical detection of
      sugars.

PMID- 21866405
TI  - Chordoma of the thoracic spine in an 89-year-old.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVE: Report the highly
      unusual presentation of thoracic spine chordoma in an 89-year-old and review
      existing literature as it impacts treatment in the elderly. Chordomas are
      infrequent tumors of the spine that commonly present during mid-adulthood at the
      spheno-occipital or sacrococcygeal junctions. The mobile spine is affected in 10
      15% of cases but chordomas are extremely rare in the thoracic spine. Chordoma
      rarely enters the differential diagnosis of spinal tumors in elderly patients,
      for whom metastases and multiple myeloma are by far the most common. METHODS: A
      case report is detailed of an 89-year-old male presenting with incapacitating
      pain and early signs of thoracic myelopathy. A lytic, expanding lesion of the T10
      vertebral body with epidural spinal cord compression was identified. In the
      absence of evidence of other primary tumor, a CT-guided needle biopsy revealed
      chordoma. A literature review of reported thoracic spine chordomas was also
      performed. RESULTS: An intralesional posterolateral resection and reconstruction
      was performed with good results and no recurrence at 13 months' follow-up. 30
      reports of thoracic spine chordomas were identified in the literature since 1902.
      Mean age of presentation at 35.7 years is earlier than for most chordomas. The
      oldest previously reported patient was 68-year-old. Neurological impairment at
      presentation is rare with the usual presenting symptom being pain. Response to
      radiation and chemotherapy is limited. 5-year survival rates range from 50 to
      60%. CONCLUSION: Chordoma is a highly uncommon epidural neoplasm of the thoracic
      spine and is vanishingly rare in elderly patients. This report documents the
      oldest reported patient with thoracic spine chordoma at 89-year-old. Their
      locally aggressive behavior typically prompts consideration of aggressive
      surgical resection. When tailored to the individual patient, such procedures are
      feasible without excessive morbidity even in elderly patients.

PMID- 21866407
TI  - Perinatal and infant mortality in term and preterm births among women with type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to estimate the risks of adverse birth
      outcomes such as stillbirth, infant death, preterm birth and pre-eclampsia in
      women with type 1 diabetes, compared with the background population. We further
      aimed to explore the risks of adverse birth outcomes in preterm and term
      deliveries separately. METHODS: By linkage of two nationwide registries, the
      Medical Birth Registry of Norway and the Norwegian Childhood Diabetes Registry,
      we identified 1,307 births among women with pregestational type 1 diabetes
      registered in the Diabetes Registry, and 1,161,092 births in the background
      population during the period 1985-2004. The ORs with 95% CIs for adverse outcome
      among women with type 1 diabetes vs the background population were estimated
      using logistic regression. RESULTS: The OR for stillbirth (>=22 weeks of
      gestation) was 3.6 (95% CI 2.5, 5.3), and for perinatal death (stillbirth or
      death in the first week of life) it was 2.9 (95% CI 2.0, 4.1). The OR for infant
      death (first year of life) was 1.9 (95% CI 1.1, 3.2). For preterm birth (< 37
      weeks of gestation) and pre-eclampsia the ORs were 4.9 (95% CI 4.3, 5.5) and 6.3
      (95% CI 5.5, 7.2), respectively. When preterm and term deliveries were analysed
      separately, the excess risk of stillbirth and infant death in women with diabetes
      was confined to term deliveries. CONCLUSIONS/INTERPRETATION: Pregestational type
      1 diabetes was associated with a considerably higher risk of adverse pregnancy
      outcomes, including infant death, compared with the background population. A
      novel finding of the study was that the increased risk was confined to term
      births.

PMID- 21866408
TI  - Physiologically based pharmacokinetic modeling of SNU-0039, an anti-Alzheimer's
      agent, in rats.
AB  - The objective of this study was to characterize the systemic and tissue kinetics
      of 2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl) benzofuran (SNU-0039), an
      inhibitor of beta-amyloid protein aggregation, in rats. Simultaneous fitting of
      the data to polyexponential equations indicated that the systemic clearance and
      steady state volume of distribution were estimated to be 0.0220 l/min/kg and 2.33
      l/kg. The clearance and volume of distribution were not dependent on the
      intravenous dose, in the range from 5 to 20 mg/kg. The tissue (i.e., the brain,
      liver, kidneys, heart, spleen, lungs, gut, muscle and adipose tissue) to plasma
      partition coefficients (K(p)) for SNU-0039 in rats ranged from a low of 0.779 +/-
      0.314 (muscle) to a high of 5.71 +/- 1.66 (liver). The recoveries of DMB were
      less than 1% of the dose for the renal and biliary excretion, indicative of minor
      involvements of these pathways in overall elimination. The fraction of bound SNU
      0039 to plasma protein was approximately 95.9% and the fraction of SNU-0039
      distributed to blood cells was approximately 45.3%. Assuming a flow-limited
      distribution, the simulated concentration profiles for SNU-0039 in the
      physiologically based pharmacokinetic model were in reasonable agreement with the
      observed concentrations in plasma and nine tissues in rats.

PMID- 21866409
TI  - Influence of the instrumented force shoe on gait pattern in patients with
      osteoarthritis of the knee.
AB  - Osteoarthritis (OA) of the knee is associated with alterations in gait. As an
      alternative to force plates, instrumented force shoes (IFSs) can be used to
      measure ground reaction forces. This study evaluated the influence of IFS on gait
      pattern in patients with knee OA. Twenty patients with knee OA walked in a gait
      laboratory on IFS and control shoes (CSs). An optoelectronic system and force
      plate were used to perform 3D gait analyses. A comparison of temporal-spatial
      gait parameters, kinematics, and kinetics was made between IFS and CS. Patients
      wearing IFS showed a decrease in walking velocity and cadence (8%), unchanged
      stride length, an increase in stance time (13%), stride time (11%) and step width
      (14%). No differences were found in knee adduction moment or knee kinematics.
      Small differences were found in foot and ankle kinematics (2-5 degrees ), knee
      transverse moments (5%), ankle frontal (3%) and sagittal moments (1%) and ground
      reaction force (1-6%). The gait of patients with knee OA was only mildly
      influenced by the IFS, due to increased shoe height and weight and a change in
      sole stiffness. The changes were small compared to normal variation and
      clinically relevant differences. Importantly, in OA patients no effect was found
      on the knee adduction moment.

PMID- 21866410
TI  - Human behaviors determine health: strategic thoughts on the prevention of chronic
      non-communicable diseases in China.
AB  - BACKGROUND: In the last three decades, people's living standards have
      significantly increased along with the rapid growth of the national economy of
      China. However, the prevalence of unhealthy behaviors and unfavorable lifestyles
      (e.g., smoking, excessive use of alcohol, physical inactivity, and unhealthy
      diets) also steadily increased, which may contribute to the growing epidemic of
      chronic non-communicable diseases (CNCDs) such as diabetes, coronary heart
      disease, stroke, and cancers. PURPOSE: To briefly summarize the major studies
      from China concerning epidemic and burden of CNCDs and unhealthy lifestyles, and
      propose intervention strategies toward unhealthy lifestyles and behaviors aiming
      for effective control of the growing epidemic of CNCDs in China. METHODS: We
      first review the major national studies addressing the epidemic and burden of
      CNCDs and unhealthy behaviors in China. Then, we aim to develop the preventive
      strategies against the increasing epidemic of CNCDs by focusing on the
      intervention campaign toward health unfavorable behaviors and lifestyles.
      RESULTS: CNCDs have posed major challenges to public health and the ongoing
      reform of health care system in China. Unhealthy lifestyles and behaviors (e.g.,
      smoking, excessive alcohol consumpsion, physical inactivity, and imbalanced
      diets) are responsible for the growing epidemic of CNCDs. Adherence to healthy
      behaviors and lifestyles is critical for maintaining physical and mental health.
      CONCLUSION: Active implementation of the population-wide intervention program of
      health education and promotion by targeting unhealthy behaviors and lifestyles
      may help to constrain the growing epidemic of CNCDs in China.

PMID- 21866411
TI  - The enduring need for the pain resource nurse (PRN) training program.
AB  - Nurses play a pivotal role in pain management but academic nursing curricula
      remain lacking in basic pain management principles. The purpose of this study was
      to evaluate the long-term impact of the City of Hope Pain Resource Nurse (PRN)
      Training Course on nursing pain management practice. An online survey, comparing
      RNs' pre- and post-training practice, assessed the long-term impact of the course
      on content application and dissemination. Participants with 1-9 years post-course
      attendance (2002-2010) were invited to complete a brief survey (N = 783).
      Respondents (N = 180; 23%) reported significant improvements in their comfort
      with basic opioid administration (p < .001). Relaxation was the most common non
      drug intervention used by respondents. Pain assessment content was most
      frequently applied to practice (97%). Most respondents (89%) disseminated course
      content to others within their own institutions. PRN-trained nurses expressed
      improved confidence in pain management and attributed course content to the
      improvement in their practice behavior.

PMID- 21866412
TI  - Important considerations for recruiting women to cancer genetics studies in
      Puerto Rico.
AB  - A goal of the Minority Institution/Cancer Center Partnership between the Ponce
      School of Medicine in Puerto Rico and the H. Lee Moffitt Cancer Center & Research
      Institute in Florida is to provide cross-cultural training in cancer research.
      This is achieved through a collaborative summer exchange program, which provides
      US students with an opportunity to conduct research in Puerto Rico. As part of
      this program, students recruited participants and collected data for a study to
      enhance the understanding of sociocultural factors among Puerto Rican women
      regarding genetic testing for hereditary breast/ovarian cancer. Limited studies
      have examined cancer genetics issues among Latinos, particularly those specific
      to the various Latino subgroups, such as Puerto Ricans. As a result of the
      student training experience, culturally appropriate strategies for the
      recruitment of women in Puerto Rico have been identified. These recommendations
      can inform the design of cancer research projects and interventions targeting the
      Puerto Rican population.

PMID- 21866413
TI  - Implementing a multi-professional web-based learning environment for a
      comprehensive cancer centre: obstacles, solutions and reflections.
AB  - There is an urgent need for efficient cancer education programmes to promote safe
      practice in a comprehensive cancer centre. Educational practice has developed
      historically in an unplanned and inefficient way. Developments in educational
      theory and information technology provide an opportunity to develop systems with
      better educational methodology, better efficiency and potential for better impact
      on safety outcomes. We have developed such a programme at St. George
      Comprehensive Cancer Centre in Sydney, Australia, and describe here our
      experience in the first 2 years of implementing such a programme. In this
      article, we describe the programme, the obstacles and solutions we encountered
      and our reflections on the journey so far.

PMID- 21866414
TI  - Thyroid hormone-regulated expression of nuclear lamins correlates with
      dedifferentiation of intestinal epithelial cells during Xenopus laevis
      metamorphosis.
AB  - In the Xenopus laevis intestine during metamorphosis, which is triggered by
      thyroid hormone (TH), the adult epithelium develops and replaces the larval one
      undergoing apoptosis. We have previously shown that progenitor/stem cells of the
      adult epithelium originate from some differentiated larval epithelial cells. To
      investigate molecular mechanisms underlying larval epithelial dedifferentiation
      into the adult progenitor/stem cells, we here focused on nuclear lamin A (LA) and
      lamin LIII (LIII), whose expression is generally known to be correlated with the
      state of cell differentiation. We analyzed the spatiotemporal expression of LA
      and LIII during X. laevis intestinal remodeling by reverse transcription PCR,
      Western blotting, and immunohistochemistry. At the onset of natural
      metamorphosis, when the adult epithelial progenitor cells appear as small islets,
      the expression of LA is down-regulated, but that of LIII is up-regulated only in
      the islets. Then, as the adult progenitor cells differentiate, the expression of
      LA is up-regulated, whereas that of LIII is down-regulated in the adult cells. As
      multiple intestinal folds form, adult epithelial cells positive for LIII become
      restricted only to the troughs of the folds. In addition, we have shown that TH
      up- or down-regulates the expression of these lamins in the premetamorphic
      intestine as during natural metamorphosis. These results indicate that TH
      regulated expression of LA and LIII closely correlates with dedifferentiation of
      the epithelial cells in the X. laevis intestine, suggesting the involvement of
      the lamins in the process of dedifferentiation during amphibian metamorphosis.

PMID- 21866415
TI  - Epidemiology of psychiatric disorders in very young children in a Romanian
      pediatric setting.
AB  - A growing literature demonstrates that early clinical intervention can reduce
      risks of adverse psychosocial outcomes. A first step necessary for developing
      early intervention services is to know the prevalence of clinical disorders,
      especially in systems that are rebuilding, such as Romania, where the mental
      health system was dismantled under Ceausescu. No epidemiologic studies have
      examined prevalence of psychiatric disorders in young children in Romania. The
      objective of this study was to determine the prevalence of psychiatric disorders
      in Romanian children 18-60 months in pediatric settings. Parents of 1,003
      children 18-60 months in pediatric waiting rooms of two pediatric hospitals
      completed background information, the Child Behavior Checklist (CBCL). A subgroup
      over-sampled for high mental health problems were invited to participate in the
      Preschool Age Psychiatric Assessment. Rates of mental health problems were
      similar to the US norms on the CBCL. The weighted prevalence of psychiatric
      disorders in these children was 8.8%, with 5.4% with emotional disorders and 1.4%
      with behavioral disorders. Comorbidity occurred in nearly one-fourth of the
      children with a psychiatric disorder and children who met diagnostic criteria had
      more functional impairment than those without. Of children who met criteria for a
      psychiatric disorder, 10% of parents were concerned about their child's emotional
      or behavioral health. This study provides prevalence rates of psychiatric
      disorders in young Romanian children, clinical characteristic of the children and
      families that can guide developing system of care. Cultural differences in
      parental report of emotional and behavioral problems warrant further examination.

PMID- 21866416
TI  - Deliberate self-harm behaviors in Chinese adolescents and young adults.
AB  - The aim of this paper was to describe the prevalence of deliberate self-harm
      (DSH) and to determine the socio-demographic, behavioral, and psychological
      correlates of DSH behaviors in Chinese adolescents and young adults in a
      representative sample of the general population. The data were obtained from an
      epidemiologic study involving adolescents and young adults from junior and senior
      schools and colleges located in eight provinces of China. A total of 17,622 cases
      were retained for analysis. The relationship between the explanatory variables
      with self-harm was analyzed using a Pearson chi (2) test and a multinomial
      logistic regression model. A total of 3,001 (17.0%) students reported that they
      had harmed themselves deliberately in the past 12 months. The act of DSH
      occurring 1 and >2 times accounted for 4.2% (742) and 12.8% (2,259) of all
      respondents, respectively. The most frequently reported form of DSH was self
      hitting. If the reference category was No DSH, the findings indicated that family
      composition, father's education, perceived family economic status, cigarette use,
      perceived body image, and higher scores in depression scales were important
      concomitants of repeat-incidents of DSH. The students, in western areas, who were
      younger, reported that having unhealthy weight control behaviors, and alcohol use
      had a higher risk for both types of DSH. Regarding students of age 15-18 years
      perceived body image (too fat), having unhealthy weight control behaviors or a
      high level of depression symptoms demonstrated an elevated risk for repeat
      incident DSH when single-incident DSH was used as the reference category, whereas
      the students in middle area reported family composition (both parents), education
      of the father (less than college) or alcohol use had a decreased risk for repeat
      incident DSH. The results of this study suggest that both types of DSH are
      associated with other wide-ranging problems in the students' lives. Despite their
      common features, these phenomena also differed from each other. It is necessary
      to investigate the possible neurobiologic underpinnings of DSH within a
      longitudinal study to enhance the knowledge of this behavior.

PMID- 21866417
TI  - Pancreatic adenocarcinoma in paraduodenal pancreatitis: a note of caution for
      conservative treatments.
AB  - Paraduodenal pancreatitis in heterotopic pancreas is a rare condition and few
      cases of malignant transformation are described. A case of cystic dystrophy of
      the duodenal wall in heterotopic pancreas complicated with pancreatic
      adenocarcinoma is described. Computed tomography, magnetic resonance and
      endoscopic ultrasonography failed to show preoperatively, the locally advanced
      adenocarcinoma raising reasonable doubts on the effectiveness and safety of
      conservative treatments for paraduodenal pancreatitis.

PMID- 21866420
TI  - The classic: On the significance of the architecture of the spongy substance for
      the question of bone growth: a preliminary publication. 1869.

PMID- 21866419
TI  - Microparticles: a critical component in the nexus between inflammation, immunity,
      and thrombosis.
AB  - Plasma membrane remodeling characterized by phosphatidylserine exposure and
      consecutive microparticle (MP) shedding is an ubiquitous process enabling the
      clearance of senescent cells and the maintenance of tissue homeostasis. MPs are
      released as fragments from the budding plasma membrane of virtually all
      eukaryotic cell types undergoing stimulation or apoptosis and may be considered a
      broad primitive response to stress. MP release is dependent on cytoskeleton
      degradation pathways involving caspases, requires a sustained increase in
      intracellular calcium triggering K+ and Cl- efflux and is possibly tuned by
      mitochondria permeability changes. Because they convey a broad spectrum of
      bioactive molecules, circulating MPs may serve as shuttles promoting cellular
      cross talk in various pathological settings such as inflammation or immunity
      induced thrombotic disorders. If the drastic shedding of procoagulant MPs appears
      clearly noxious in thrombotic disorders or in some models of inflammation-induced
      coagulopathy, this does not necessarily endorse their invariably harmful nature.
      In the vessel, endothelial cytoprotection reported in the early regulation of
      inflammation-induced coagulopathy is emblematic of the beneficial effects
      provided by MPs. In addition, MPs would prove beneficial in the prevention of
      blood leakage. Because of their multiple properties that are characteristic of a
      private response of the parental cell, MPs could act as cytoprotective and anti
      inflammatory agents through the delivery of activated protein C or annexin 1 and
      could contribute to the limitation of vascular hyporeactivity. Owing to their
      ability to cargo bioactive signals, MPs could be viewed as an integrated
      communication network enabling the coordination of complex cellular responses in
      biological fluids and the maintenance of the homeostasis equation. A better
      understanding of the molecular mechanisms involved in MP shedding would pave the
      way of a new pharmacological approach aiming at the control of MP-driven cellular
      responses.

PMID- 21866421
TI  - Two-stage exchange arthroplasty for infected total knee arthroplasty: predictors
      of failure.
AB  - BACKGROUND: In North America, a two-stage exchange arthroplasty remains the
      preferred surgical treatment for chronic periprosthetic joint infection (PJI).
      Currently, there are no proper indicators that can guide orthopaedic surgeons in
      patient selection for two-stage exchange or the appropriate conditions in which
      to reimplant. QUESTIONS/PURPOSES: To identify (1) the rate of recurrent PJI after
      two-stage exchange and (2) the role of 15 presurgical and 11 operative factors in
      influencing the outcome of two-stage revision. PATIENTS AND METHODS: From a
      prospective database we identified 117 patients who had undergone two-stage
      exchange arthroplasty for PJI of the knee from 1997 to 2007. Failure of two-stage
      revision was defined as any treated knee requiring further treatment for PJI. We
      identified 15 presurgical and 11 surgical factors that might be related to
      failure. Minimum followup was 2 years (average, 3.4 years; range, 2-9.4 years).
      RESULTS: Thirty-three of 117 reimplantations (28%) required reoperation for
      infection. Age, gender, body mass index, and comorbidity indices were similar in
      both groups. Multivariate analysis provided culture-negative (odds ratio [OR],
      4.5; 95% confidence interval [CI], 1.3-15.7), methicillin-resistant organisms
      (OR, 2.8; 95% CI, 0.8-10.3), and increased reimplantation operative time (OR,
      1.01; 95% CI, 1.0-1.03) as predictors of failure. ESR and CRP values at the time
      of reimplantation and time from resection to reimplantation were not predictors.
      CONCLUSIONS: Our observations suggest the failure rate after two-stage
      reimplantation for infected TKA is relatively high. Culture-negative or
      methicillin-resistant PJI increases the risk of failure over four- and twofold,
      respectively. We identified no variables that would guide the surgeon in
      identifying acceptable circumstances in which to perform the second stage. LEVEL
      OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21866422
TI  - Precontoured superior locked plating of distal clavicle fractures: a new
      strategy.
AB  - BACKGROUND: The ideal management of fractures of the distal third of the clavicle
      remains a topic of debate. Locked plating is a new treatment method but is not
      yet widely studied. QUESTIONS/PURPOSES: We therefore determined union rates,
      function, and complications treated with locked plating. PATIENTS AND METHODS: We
      retrospectively reviewed 20 patients with Neer Type II distal clavicle fractures.
      All patients were treated with superior locked plating augmented with suture
      cerclage or screw fixation into the coracoid when there were concerns with screw
      purchase in the lateral fragment. Union was assessed radiographically and
      function was reported in terms of American Shoulder and Elbow Surgeons (ASES)
      scores and motion. Sixteen of 20 patients were followed for a minimum of 1 year;
      four of the patients with less than 1 year followup were included only for
      reporting of complications. The 16 patients were followed a minimum of 12 months
      (average, 30.7 months; range, 13-87 months). RESULTS: Union occurred in 15 of 16
      (94%) patients. Average forward elevation and external rotation were 165.6
      degrees  (range, 115 degrees -180 degrees ) and 58.8 degrees  (range, 20 degrees 
      90 degrees ), respectively. The average ASES score at the most recent followup
      was 79.0 (range, 33.3-100). Complications occurred in two patients. One patient
      developed an infected nonunion and a second patient sustained a peri-implant
      fracture. CONCLUSIONS: Acute unstable distal clavicle fractures can be treated
      with superior locking plates with union rates, ASES scores, and ROM that are
      comparable to similar studies in the literature. The treatment method described
      allows supplemental fixation such as suture augmentation or a coracoclavicular
      screw. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 21866423
TI  - Non-erythroid beta spectrin interacting proteins and their effects on spectrin
      tetramerization.
AB  - With yeast two-hybrid methods, we used a C-terminal fragment (residues 1697-2145)
      of non-erythroid beta spectrin (betaII-C), including the region involved in the
      association with alpha spectrin to form tetramers, as the bait to screen a human
      brain cDNA library to identify proteins interacting with betaII-C. We applied
      stringent selection steps to eliminate false positives and identified 17 proteins
      that interacted with betaII-C (IP(betaII-C) s). The proteins include a fragment
      (residues 38-284) of "THAP domain containing, apoptosis associated protein 3,
      isoform CRA g", "glioma tumor suppressor candidate region gene 2" (residues 1
      478), a fragment (residues 74-442) of septin 8 isoform c, a fragment (residues
      704-953) of "coatomer protein complex, subunit beta 1, a fragment (residues 146
      614) of zinc-finger protein 251, and a fragment (residues 284-435) of syntaxin
      binding protein 1. We used yeast three-hybrid system to determine the effects of
      these betaII-C interacting proteins as well as of 7 proteins previously
      identified to interact with the tetramerization region of non-erythroid alpha
      spectrin (IP(alphaII-N) s) [1] on spectrin tetramer formation. The results showed
      that 3 IP(betaII-C) s were able to bind betaII-C even in the presence of alphaII
      N, and 4 IP(alphaII-N) s were able to bind alphaII-N in the presence of betaII-C.
      We also found that the syntaxin binding protein 1 fragment abolished alphaII-N
      and betaII-C interaction, suggesting that this protein may inhibit or regulate
      non-erythroid spectrin tetramer formation.

PMID- 21866424
TI  - Targeting MET by tyrosine kinase inhibitor suppresses growth and invasion of
      nasopharyngeal carcinoma cell lines.
AB  - Nasopharyngeal carcinoma (NPC) represents a common cancer in endemic areas with
      high invasive and metastatic potential. It is now known that the HGF-MET
      signaling pathway plays an important role in mediating the invasive growth of
      many different types of cancer, including head and neck squamous cell carcinoma.
      HGF has been shown to stimulate NPC cell growth and invasion in cell line model.
      The current study aims at demonstrating the effect of MET inhibition by small
      molecule tyrosine kinase inhibitor PHA665752 on the growth and invasive potential
      of NPC cell lines. NPC cell lines were used for immunohistochemistry for the MET
      protein, as well as western blot analysis on MET together with its downstream
      cascade signaling proteins after treatment with PHA665752. The effect on cell
      growth, migration and invasion after PHA665752 treatment was also studied. MET
      inhibition by PHA665752 resulted in highly significant inhibition on NPC cell
      growth, migration and invasion in vitro. Down-regulation of phospho-MET, phospho
      Akt, phospho-MAPK, phospho-STAT3, cyclin D1, beta-catenin and PCNA was detected
      in NPC cells after PHA665752 treatment. MET inhibition with tyrosine kinase
      inhibitor resulted in suppression of NPC cell growth and invasive potential via
      down-regulation of a variety of signaling onco-proteins. MET is an important
      therapeutic target for NPC that warrants further studies and clinical trials.

PMID- 21866426
TI  - Self-care and end of life care--patients' and carers' experience a qualitative
      study utilising serial triangulated interviews.
AB  - PURPOSE: This study aimed to understand patient and carer experiences of end of
      life care and to explore how patients care for themselves at the end of life in
      Scotland. RESEARCH QUESTIONS: (1) From the perspectives of patients and carers,
      what are their experience of advanced cancer and end of life care? (2) What self
      care strategies enable patient and carers to cope with their end of life care?
      METHODS: This paper reports a qualitative study using in-depth, unstructured
      serial interviews involving collaboration with and participation of people
      affected by advanced cancer. The study was a 2-year, three-phase study with
      multiple methods of data collection. The study was conducted in the Highlands and
      West of Scotland including rural, remote and socially deprived areas. Patient
      experience data were collected from 20 patients as well as their main carer and
      the health professional who they perceived had given them the most support.
      Triangulating data in this way allowed the totality of the patient experience to
      be captured. A total of 71 interviews were conducted. Data were analysed both
      within and across cases using framework analysis with the aid of QSR NVIVO 7.
      RESULTS: Maintaining normality and preparing for death were the two most
      important areas, for the patients in the study, as far as their self-care was
      concerned. Patients wished support that enabled them to maintain their
      independence and remain at home. People managed their illness both physically and
      emotionally; managing and adjusting to their lack of independence and keeping
      control were keys to most participants. CONCLUSIONS: Self-care is important to
      this group of people. People receiving end of life care want to and are able to
      engage in research. The findings are timely and relevant to current changes in
      palliative care policy and practice.

PMID- 21866427
TI  - Ondine's curse: anesthesia for laparoscopic implantation of a diaphragm pacing
      stimulation system.
AB  - PURPOSE: Central alveolar hypoventilation syndrome (CAHS) is a rare disease
      characterized by the loss of autonomic control of breathing. This condition
      causes hypoventilation and obstruction during sleep. Throughout their lives,
      these patients require ventilatory assistance by means of positive pressure
      ventilation to their lungs via mask, tracheotomy, or other means, such as phrenic
      nerve pacers. The diaphragm pacing stimulation system (DPSS) is a new treatment
      where electrodes are implanted into the diaphragm and cause contraction on
      stimulation. The DPSS has been used successfully in tetraplegic patients and
      patients suffering from amyotrophic lateral sclerosis (ALS). It has been shown to
      improve quality of life and to extend survival in patients with advanced
      respiratory muscle weakness. In our case, we describe the perioperative
      management of an adult patient with acquired CAHS who presented for laparoscopic
      DPSS insertion. CLINICAL FEATURES: Our patient was a 50-yr-old female who
      developed CAHS at age thirteen after contracting encephalitis. Since the onset of
      her disease, she had been managed with positive pressure ventilation to her lungs
      via mask. Due to her longstanding disease, she presented with pulmonary
      hypertension and cor pulmonale and was scheduled for laparoscopic DPSS
      implantation. Our anesthetic technique included a total intravenous technique
      with remifentanil and propofol, and her trachea was intubated without the use of
      muscle relaxants. The pacemakers were switched on when the patient emerged from
      anesthesia, which provided her with ventilatory support and allowed us to
      extubate her trachea. CONCLUSION: We present the successful anesthetic management
      of an adult patient with CAHS undergoing laparoscopic DPSS insertion.

PMID- 21866425
TI  - A computational model of fMRI activity in the intraparietal sulcus that supports
      visual working memory.
AB  - A computational model was developed to explain a pattern of results of fMRI
      activation in the intraparietal sulcus (IPS) supporting visual working memory for
      multiobject scenes. The model is based on the hypothesis that dendrites of
      excitatory neurons are major computational elements in the cortical circuit.
      Dendrites enable formation of a competitive queue that exhibits a gradient of
      activity values for nodes encoding different objects, and this pattern is stored
      in working memory. In the model, brain imaging data are interpreted as a
      consequence of blood flow arising from dendritic processing. Computer simulations
      showed that the model successfully simulates data showing the involvement of
      inferior IPS in object individuation and spatial grouping through representation
      of objects' locations in space, along with the involvement of superior IPS in
      object identification through representation of a set of objects' features. The
      model exhibits a capacity limit due to the limited dynamic range for nodes and
      the operation of lateral inhibition among them. The capacity limit is fixed in
      the inferior IPS regardless of the objects' complexity, due to the normalization
      of lateral inhibition, and variable in the superior IPS, due to the different
      encoding demands for simple and complex shapes. Systematic variation in the
      strength of self-excitation enables an understanding of the individual
      differences in working memory capacity. The model offers several testable
      predictions regarding the neural basis of visual working memory.

PMID- 21866428
TI  - Physician professional behaviour affects outcomes: a framework for teaching
      professionalism during anesthesia residency.
AB  - PURPOSE: In this review, we examine the association between physician
      professional behaviour and indicators measuring patient outcomes and satisfaction
      with care as well the potential for complaints, discipline, and litigation
      against physicians. We also review issues related to the structured teaching of
      professionalism to anesthesia residents, including resident evaluation. SOURCE: A
      search of the OVID Medline and PubMed databases was carried out using keywords
      relevant to the topics under consideration. Program directors of Canadian
      anesthesiology training programs were also surveyed to assess the current state
      of professionalism training and evaluation in their programs. PRINCIPAL FINDINGS:
      Unprofessional behaviour is frequently manifested in practice by medical
      students, residents, and physicians, and it is associated with personality
      characteristics that are evident early in training. There is a correlation
      between unprofessional physician behaviours and patient dissatisfaction,
      complaints, and lawsuits as well as adverse outcomes of care. Physician health
      and workplace relationships are negatively impacted by such behaviours. Canadian
      program directors recognize the need to approach the teaching of professionalism
      in an organized fashion during physician training. CONCLUSIONS: A framework is
      provided for defining behavioural expectations, and mechanisms are offered for
      teaching and evaluating behaviours and responding to individuals with behaviours
      that persistently breach defined expectations. There is a need to define
      explicitly not only the expectations for behaviour but also the processes by
      which the behaviours will be assessed and documented. In addition, emphasis is
      placed on the nature, order, and magnitude of the responses to behaviours that do
      not meet expectations.

PMID- 21866429
TI  - Desflurane and neural control of airway tone.

PMID- 21866430
TI  - Cerebral oximetry desaturation during shoulder surgery performed in a sitting
      position under regional anesthesia.
AB  - PURPOSE: Hypotension in the sitting position may reduce cerebral perfusion and
      oxygenation. We prospectively determined the incidence of cerebral oximetry
      (rSO2) desaturation in seated patients undergoing ambulatory shoulder
      arthroscopy. METHODS: A cohort of 99 patients received regional anesthesia and
      intravenous sedation, and their blood pressure was recorded every five minutes.
      Hypotension was defined as the occurrence of any of the following: > 30% decline
      in mean arterial pressure (MAP), systolic blood pressure < 90 mmHg, or MAP <66
      mmHg. Cerebral desaturation was defined as a > 20% decrease in rSO2 from
      baseline. The association of rSO2 desaturation with potential risk factors was
      examined by the generalized estimating equation to account for within patient
      correlation and multiple observations per patient. We fitted desaturation with
      three models: 1) unadjusted (i.e., hypotension as sole regressor); 2) time-trend
      adjusted; and 3) baseline-factors adjusted model. RESULTS: Hypotension occurred
      in 76% of observations (mean duration 4,261 sec), but cerebral desaturation was
      seen in only 0.77% of observations (mean duration 426 sec). Ninety-nine percent
      of patients experienced hypotension, but cerebral desaturation occurred in only
      10%. By unadjusted modelling, hypotension was associated with cerebral
      desaturation (odds ratio = 3.21; P = 0.02). Once time-trend adjusted, cerebral
      desaturation was associated with time from baseline but not with hypotension (P =
      0.14). When adjusted for baseline factors, the analysis demonstrated a non
      significant association with hypotension (P = 0.34) but a significant association
      with the presence of risk factors for cerebrovascular disease (P = 0.01).
      CONCLUSIONS: Despite frequent hypotension in the sitting position, rSO2
      desaturation was uncommon during shoulder arthroscopy performed in the sitting
      position with regional anesthesia.

PMID- 21866431
TI  - The difficult airway in obstetrical anesthesia: advocacy to improve the quality
      of assessment.

PMID- 21866432
TI  - Hydrocortisone reduces postoperative shivering following day care knee
      arthroscopy.
AB  - PURPOSE: Postoperative shivering is commonly observed in patients after general
      anesthesia. A double-blind randomized controlled trial was conducted in patients
      undergoing day care knee arthroscopy to test the hypothesis that a single
      intraoperative dose of hydrocortisone would prevent or attenuate postoperative
      shivering. METHODS: One hundred and twenty patients were given a nitrous oxide
      isoflurane-remifentanil anesthetic. Approximately ten minutes before the end of
      anesthesia, they were randomized to receive normal saline (Control group; n =
      40); hydrocortisone 1 mg.kg(-1) iv (Hydrocortisone-1 group; n = 40), or
      hydrocortisone 2 mg.kg(-1) iv (Hydrocortisone-2 group; n = 40). Postoperative
      shivering was graded by a blinded observer using a five-point scale: Grade 0:
      none; Grade 1: one or more areas of piloerection but without visible muscular
      activity; Grade 2: visible muscular activity confined to one muscle group; Grade
      3: same as Grade 2 but in more than one muscle group; and Grade 4: gross muscular
      activity involving the entire body. RESULTS: Shivering (Grades 1-4) was observed
      in 33 patients (82%) in the Control group, 13 patients (32%) in the
      Hydrocortisone-1 group (P < 0.001 compared with the Control group), and eight
      patients (20%) in the Hydrocortisone-2 group (P < 0.001 compared with the Control
      group). The overall incidence of shivering was similar in the Hydrocortisone-1
      and Hydrocortisone-2 groups. CONCLUSIONS: This study shows that hydrocortisone (1
      2 mg.kg(-1) iv) provides effective prophylaxis against postoperative shivering in
      patients undergoing day care knee arthroscopy under general anesthesia.

PMID- 21866434
TI  - Assessment of phenanthrene bioavailability in aged and unaged soils by mild
      extraction.
AB  - It has become apparent that the threat of an organic pollutant in soil is
      directly related to its bioavailable fraction and that the use of total
      contaminant concentrations as a measure of potential contaminant exposure to
      plants or soil organisms is inappropriate. In light of this, non-exhaustive
      extraction techniques are being investigated to assess their appropriateness in
      determining bioavailability. To find a suitable and rapid extraction method to
      predict phenanthrene bioavailability, multiple extraction techniques (i.e., mild
      hydroxypropyl-beta-cyclodextrin (HPCD) and organic solvents extraction) were
      investigated in soil spiked to a range of phenanthrene levels (i.e., 1.12, 8.52,
      73, 136, and 335 MUg g( - 1) dry soil). The bioaccumulation of phenanthrene in
      earthworm (Eisenia fetida) was used as the reference system for bioavailability.
      Correlation results for phenanthrene suggested that mild HPCD extraction was a
      better method to predict bioavailability of phenanthrene in soil compared with
      organic solvents extraction. Aged (i.e., 150 days) and fresh (i.e., 0 day) soil
      samples were used to evaluate the extraction efficiency and the effect of soil
      contact time on the availability of phenanthrene. The percentage of phenanthrene
      accumulated by earthworms and percent recoveries by mild extractants changed
      significantly with aging time. Thus, aging significantly reduced the earthworm
      uptake and chemical extractability of phenanthrene. In general, among organic
      extractants, methanol showed recoveries comparable to those of mild HPCD for both
      aged and unaged soil matrices. Hence, this extractant can be suitable after HPCD
      to evaluate risk of contaminated soils.

PMID- 21866435
TI  - Two-dimensional and Doppler echocardiographic findings in healthy non-sedated red
      eared slider terrapins (Trachemys scripta elegans).
AB  - Echocardiographic evaluation was performed in six healthy young adult non-sedated
      terrapins (Trachemys scripta elegans). The best imaging quality was obtained
      through the right cervical window. Base-apex inflow and outflow views were
      recorded, ventricular size, ventricular wall thickness and ventricular outflow
      tract were measured, and fractional shortening was calculated. Pulsed-wave
      Doppler interrogation enabled the diastolic biphasic atrio-ventricular flow and
      the systolic ventricular outflow patterns to be recorded. The following Doppler
      derived functional parameters were calculated: early diastolic (E) and late
      diastolic (A) wave peak velocities, E/A ratio, ventricular outflow systolic peak
      and mean velocities and gradients, Velocity-Time Integral, acceleration and
      deceleration times, and Ejection Time. For each parameter the mean, standard
      deviation and 95% confidence interval were calculated. Echocardiography resulted
      as a useful and easy-to-perform diagnostic tool in this poorly known species that
      presents difficulties during evaluation.

PMID- 21866433
TI  - Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee
      guidelines.
AB  - PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of
      Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium
      induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition
      of CIN, the choice of contrast medium, the prophylactic measures used to reduce
      the incidence of CIN, and the management of patients receiving metformin. Key
      Points * Definition, risk factors and prevention of contrast medium induced
      nephropathy are reviewed. * CIN risk is lower with intravenous than intra
      arterial iodinated contrast medium. * eGFR of 45 ml/min/1.73 m (2) is CIN risk
      threshold for intravenous contrast medium. * Hydration with either saline or
      sodium bicarbonate reduces CIN incidence. * Patients with eGFR >= 60 ml/min/1.73
      m (2) receiving contrast medium can continue metformin normally.

PMID- 21866436
TI  - Calculation of chemical shift anisotropy in proteins.
AB  - Individual peptide groups in proteins must exhibit some variation in the chemical
      shift anisotropy (CSA) of their constituent atoms, but not much is known about
      the extent or origins of this dispersion. Direct spectroscopic measurement of CSA
      remains technically challenging, and theoretical methods can help to overcome
      these limitations by estimating shielding tensors for arbitrary structures. Here
      we use an automated fragmentation quantum mechanics/molecular mechanics (AF
      QM/MM) approach to compute (15)N, (13)C' and (1)H chemical shift tensors for
      human ubiquitin and the GB1 and GB3 fragments of staphylococcal protein G. The
      average and range of variation of the anisotropies is in good agreement with
      experimental estimates from solid-state NMR, and the variation among residues is
      somewhat smaller than that estimated from solution-state measurements. Hydrogen
      bond effects account for much of the variation, both between helix and sheet
      regions, and within elements of secondary structure, but other effects (including
      variations in torsion angles) may play a role as well.

PMID- 21866437
TI  - The transition from three-dimensional to two-dimensional foam structures.
AB  - A two-dimensional foam consists of a monolayer of bubbles. It can be created by
      squeezing the more familiar three-dimensional foam between two parallel glass
      plates. We describe and explain the minimum plate separation H which must be
      reached to fully effect the transition from three- to two- dimensional foam. We
      find that H/V(1/3) is close to one, where V is the average bubble volume, and
      increases slightly when the side-walls of the container are taken into account.

PMID- 21866442
TI  - Single-incision vaginal approach to treat cystocele and vault prolapse with an
      anterior wall mesh anchored apically to the sacrospinous ligaments.
AB  - INTRODUCTION AND HYPOTHESIS: The safety and early efficacy of a new technique to
      treat cystocele and/or concomitant apical prolapse through a single vaginal
      incision with a lightweight mesh anchored apically bilaterally to the
      sacrospinous ligaments is reported. METHODS: Women with anterior compartment
      and/or apical prolapse >= stage II underwent repair through a single anterior
      vaginal wall incision with the Anterior Elevate System (AES). The technique
      utilizes a lightweight (24 g/m(2)) type I mesh anchored to the sacrospinous
      ligaments via two mesh arms with small self-fixating tips. The bladder neck
      portion of the graft is anchored to the obturator internus with similar self
      fixating tips. The apical portion of the graft is adjustable to vaginal length
      prior to locking in place. Outcome measures included prolapse degree at last
      follow-up visit, intra/post-operative complications, and QOL assessments.
      RESULTS: Sixty patients were implanted with average follow-up of 13.4 months
      (range 3-24 months). Mean pre-op Ba was +2.04 +/- 1.3 and C -2.7 +/- 2.9. Average
      blood loss was 47 cc and average hospital stay was 23 h. Sixty-two percent of
      patients had concomitant sling for SUI. Mean post-op Ba is -2.45 +/- 0.9 and C 
      8.3 +/- 0.9. There was no statistical difference in pre- to post-op TVL.
      Objective cure rate at current follow-up is 91.7% (<= stage 1). To date, there
      have been no mesh extrusions. No patients have reported significant buttock or
      leg pain. No patients have required surgical revision for any reason. CONCLUSION:
      The AES is a minimally invasive technique to treat anterior compartment and/or
      apical prolapse through a single vaginal incision. Initial results show the
      procedure to be safe and early efficacy is promising. Longer-term follow-up is
      ongoing.

PMID- 21866438
TI  - EGFR mutant lung cancer.
AB  - Thoracic oncologists traditionally have made treatment decisions based upon tumor
      histology, distinguishing non-small cell lung cancer (NSCLC) from small cell lung
      cancer (SCLC). However, recent data has revealed that at least one histological
      subtype of NSCLC, lung adenocarcinoma comprises multiple molecularly distinct
      diseases. Lung adenocarcinoma subsets now can be defined by specific 'driver'
      mutations in genes encoding components of the EGFR signaling pathway.
      Importantly, these mutations have implications regarding targeted therapy. Here,
      we focus on EGFR mutant NSCLC-a prime example of a clinically relevant molecular
      subset of lung cancer, with defined mechanisms of drug sensitivity, primary drug
      resistance, and acquired resistance to EGFR tyrosine kinase inhibitors. Efforts
      are now being made to overcome mechanisms of acquired resistance. These findings
      illustrate how knowledge about the genetic drivers of tumors can lead to rational
      targeted therapy for individual patients.

PMID- 21866443
TI  - Gamma-radiation induced modifications in substrate specificity of glucose
      dehydrogenase and carbon source utilization pattern of phosphate-solubilizing
      Pantoea strains.
AB  - Glucose, maltose, and mannose as sole carbon sources, induced synthesis of
      glucose dehydrogenase (GDH) in three strains of Pantoea with specific activities
      from 0.14 to 0.6 U/mg proteins. Utilization of lactose indicated that the enzyme
      belongs to GDH type B isozyme. Of mutant clones, developed through radiation
      mutagenesis, P2-M2 utilized ribose with GDH specific activity of 0.57 U/mg
      protein, P4-M3 grown on glucose gave 1.5 U/mg protein and P4-M5 had high
      activities, when grown on galactose, maltose, and lactose. Clones P3-M2 and P2-M5
      had versatile utilization of sugars and released higher amounts of P from tri
      calcium phosphate and can be efficiently used for biofertilization.

PMID- 21866444
TI  - [Application of biotherapy in recurrent or metastatic gastric cancer].
AB  - Post-operative recurrence and metastasis remain the leading causes of death for
      patients with gastric cancer. The major determinants of recurrence and metastasis
      are the biological characteristics of cancer cells and the immunological status
      of the patients. In recent years, due to the target-specificity, biotherapy has
      yielded efficacious responses in diverse clinical applications for cancer
      treatment, partially for the treatment of recurrence and metastasis of gastric
      cancer. However, because of the high diversities in clinical manifestations,
      patients' condition, and tumor's characteristics, there is no ideal strategy of
      biotherapy established for the prevention and treatment of recurrence and
      metastasis in gastric cancer. Therefore, a lot of work need to be done in basic
      research and clinical trial to make the biotherapy effective in treatment of
      gastric cancer recurrence.

PMID- 21866445
TI  - [Precaution of over or under treatment for colorectal cancer].
AB  - Insufficient treatment and overtreatment in the management of colorectal cancer
      greatly influence patients' outcome. The clinicopathological stage of carcinoma
      located in colon and rectum is different for anatomical differences. The
      indication of adjuvant chemotherapy varies in colon or rectal cancer. Locally
      advanced rectal cancer should receive neoadjuvant treatment, however, the optimal
      regimen is still controversial.

PMID- 21866446
TI  - [Surgical outcomes for 187 patients with locally recurrent rectal cancer and
      analysis of prognostic factors].
AB  - OBJECTIVE: To evaluate the surgical outcomes for patients with locally recurrent
      rectal cancer (LRRC) and to analyze the prognostic factors. METHODS: Clinical
      data of 187 patients with LRRC undergoing surgery at the First Hospital of peking
      University from January 1985 to December 2009 were retrospectively reviewed.
      RESULTS: Procedures performed included local resection(n=34), abdominoperineal
      resection (n=35), posterior pelvic exenteration (n=17), total pelvic
      exenteration(TPE, n=98), TPE with sacrectomy (n=2), and TPE with internal
      hemipelvectomy (n=1). The operation was R0 in 87 patients, R1 in 60, and R2 in
      40. The degree of radical resection was associated with the initial surgery and
      the degree of pelvic fixation (P<0.05). The pelvic recurrence rate was
      44.4%(64/144). The operative morbidity and mortality were 47.5%(89/187) and
      2.7%(5/187), respectively. The overall 3- and 5-year survival rates were 42.2%
      and 30.7%, respectively. The degree of radical resection and lymph node
      metastasis were independent risk factors associated with prognosis. The 5-year
      survival rates of R0, R1 and R2 were 42.6%, 17.2% and 0, respectively(P<0.01).
      The 5-year survival rates of patients with and without lymph node metastasis were
      5.6% and 40.5%(P<0.01) respectively. CONCLUSION: Accurate evaluation of extent of
      pelvic fixation and achievement of R0 resection are critical to improve the
      surgical outcomes for LRRC.

PMID- 21866447
TI  - [Surgical treatment of recurrent colorectal carcinoma in the elderly].
AB  - OBJECTIVE: To evaluate the safety and efficacy of surgical treatment for
      recurrent colorectal carcinoma in the elderly. METHODS: The clinical and follow
      up data of 24 elderly patients with recurrent colorectal carcinoma who were
      treated between January 2000 and June 2009 at the Changhai hospital of the Second
      Military Medical University were analyzed retrospectively. RESULTS: Among the 24
      patients there were 14 men and 10 women. The mean age of the patients was 76.9 +/
      5.3 years. The local recurrence was found in 15 patients. In 9 patients, both
      distant metastases and local recurrence were found. A total of 24 patients
      received operation, including radical resection in 15 patients and palliative
      resection in 8 patients. One patient had laparotomy only because of diffuse
      metastases in the abdomen and involvement of the duodenum and common bile
      duct.The patient received stent placement in the common bile duct and
      chemotherapy after the surgery. Postoperative complication occurred in 7(29.2%)
      patients, which included ileus(n=1), pulmonary infection(n=1), urinary
      infection(n=1), wound infection(n=2), wound dehiscence(n=1), and wound fat
      liquefaction(n=1). There were no perioperative deaths. The median survival time
      was 6 months in the entire cohort. The median survival time was 33 months in
      patients undergoing radical resection, and the 1-, 3-, and 5-year survival rate
      was 71.4%, 28.6%, and 14.3%. The median survival time was 3 months in patients
      who underwent palliative resection, and the 1-year survival rate was 0. The
      difference between the two groups was statistically significant(P<0.01).
      CONCLUSION: Outcomes are acceptable after radical resection for elderly patients
      with recurrent colorectal cancer if careful preoperative evaluation and
      perioperative management are performed.

PMID- 21866448
TI  - [Analysis of splenic hilar lymph node metastasis in advanced gastric cancer and
      dissection techniques].
AB  - OBJECTIVE: To study the status of splenic hilar lymph nodes(No.4sa, No.10 or
      No.11d lymph nodes) metastasis and to investigate the proper dissection technique
      in patients with advanced gastric cancer. METHODS: A retrospective study was
      performed to investigate 590 patients who underwent D2 curative proximal or total
      gastrectomy for gastric carcinoma from January 2006 to December 2009.
      Clinicopathological factors such as sex, age, location of the primary tumor,
      tumor sizes, gross type, depth of invasion, microscopic classification,
      neoadjuvant chemotherapy and the metastasis of adjacent lymph node were analyzed
      with univariate and multivariate analysis. Influence of combined splenectomy or
      pancreatectomy on lymph node dissection was also investigated. RESULTS: The
      overall ratio of metastatic lymph node(positive lymph nodes/lymph nodes
      harvested) in the splenic hilum was 17.5%(99/565). The positive rates of No.4sa,
      No.10, No.11d lymph nodes were 17.8% (41/230), 13.9%(29/209), and 22.8%(29/127),
      respectively. A total of 7.1%(42/590) of the patients had lymph node metastasis
      in the splenic hilum. Multivariable logistic regression analysis showed that age,
      tumor size, depth of tumor invasion, positive metastasis of No.4sb lymph node
      were independent risk factors for lymph node metastasis in the splenic hilum
      region. When comparing patients undergoing combined splenectomy or
      pancreatectomy(n=23) and those who did not undergo combined organ resection
      (n=553), the ratios of metastatic lymph node in the splenic hilum were
      14.8%(4/27) and 17.2%(91/527), respectively, and the difference was not
      statistically significant(P>0.05). The postoperative complication rates were
      26.1%(6/23) and 5.4%(30/553), respectively, and the difference was statistically
      significant(P<0.05). The operative mortality rates were 4.3% and 0.9%,
      respectively, and the difference was not statistically significant(P>0.05).
      CONCLUSIONS: Metastasis to lymph nodes in the splenic hilum region in patients
      with gastric cancer possesses a certain pattern, and it is associated with tumor
      location, size, depth of invasion, and metastasis in No.4sb. Combined resection
      of the spleen or pancreas does not result in increased number of harvested lymph
      nodes or positive lymph nodes, yet is associated with higher complication rate.
      Therefore, combined organ resection should be meticulous.

PMID- 21866449
TI  - [Absorbable suture delays postoperative recurrence after bowel resection for
      Crohn disease].
AB  - OBJECTIVE: To investigate the effect of anastomosis suture on the postoperative
      recurrence in patients with Crohn disease(CD). METHODS: A total of 102 patients
      undergoing intestinal resection for CD at the Jinling Hospital of Nanjing
      University School of Medicine from Jan. 2002 to Jan. 2010 were studied
      retrospectively. The postoperative recurrence(endoscopic and clinical) in
      patients receiving intestinal anastomosis with VICRYL absorbable suture(n=48) was
      compared with that of patients sewn with normal silk suture(n=54). RESULTS: The 1
      , 2-, and 3-year accumulated clinical recurrence rates in the absorbable suture
      group and silk suture group were 6.3%, 14.6%, 22.9%, and 18.5%, 27.8%, 35.2%,
      respectively. The differences were not statistically significant(P=0.213). The 1-
      and 2-year accumulated endoscopic recurrence rates in the absorbable suture group
      and silk suture group were 14.7%, 38.2% and 22.9%, 62.9%, respectively. The
      differences were statistically significant(P=0.034). CONCLUSIONS: Compared to
      silk suture, use of absorbable suture for anastomosis may lower the risk of
      postoperative endoscopic recurrence after bowel resection in patients with CD.
      Absorbable suture should be the first choice for intestinal anastomosis in CD
      patients.

PMID- 21866450
TI  - [Clinicopathological observation of gastric cancer with pathological complete
      response following neoadjuvant chemotherapy].
AB  - OBJECTIVE: To observe the clinicopathological characteristics of gastric cancer
      with pathological complete response(pCR) following neoadjuvant chemotherapy.
      METHODS: Data of gastric cancer patients who received neoadjuvant chemotherapy
      from 2002 to 2008 in the Beijing Cancer Hospital were reviewed. Five cases were
      found to have pCR. The slides were reviewed by two experienced pathologists
      independently. Histological structure, morphology of tumor cells, morphology and
      quantity of stromal cells were evaluated. RESULTS: Structure of the gastric wall
      was distinguishable in all the 5 cases, while distortion and rupture of muscular
      layer were found in 2 cases. Exudative inflammatory reaction was present in the
      whole gastric wall including the serosa layer. Three patients had ulcerative
      lesions with epithelial layer shedding, and atypical hyperplasia was found around
      the border of the ulcer, and vascular endothelial cells were swollen. Residual
      distorted necrotic tumor cells resided in 1 case only and no residual tumor cells
      was present in the other 4 patients. Significant hyperplasia of fibroblasts was
      present in 4 cases, large amount of lymphocytes infiltration in 3 cases including
      concurrent plasma cell infiltration in 1 case, multinucleated giant cell reaction
      in the muscular layer of 1 case, and foam cells aggregation in 1 case with
      mucinous adenocarcinoma. In addition, there were 2 cases with pCR had lymph node
      metastasis. CONCLUSIONS: For cases with pCR following neoadjuvant chemotherapy,
      heterogeneity of stromal cells reaction is found in previous tumor site.
      Furthermore, the response of primary tumor does not necessarily parallel to that
      of lymph nodes.

PMID- 21866451
TI  - [Clinicopathological features and prognosis of cystic gastrointestinal stromal
      tumor].
AB  - OBJECTIVE: To investigate the clinicopathological and molecular genetic
      characteristics of gastrointestinal stromal tumor (GISTs) with significant cystic
      changes, and to assess their biological behavior. METHODS: Clinicopathological
      features of 7 patients with cystic GISTs treated at the Zhongshan Hospital of
      Fudan University from February 2005 to January 2010 were summarized
      retrospectively. The mutations status of c-kit and PDGFR-alpha were analyzed.
      RESULTS: There were 2 males and 5 females aged from 46 to 76 years old. Primary
      site of GISTs included stomach(n=4), duodenum(n=1), and small intestinal(n=2).
      Tumor size ranged from 6 to 16 cm with obviously cystic changes. Tumor cells were
      found in the solid components under microscope, of which epithelioid cell type
      were found in 4 case and spindle cell type in 3 cases. The mitotic figures were
      no more than 3/50 HPF in all the patients. According to the NIH criteria, 4 were
      high-risk and 3 were low-risk. Based on morphological characteristics, 3 cases
      were as borderline tumor, 3 moderate-risk, and 1 moderate-risk. Gene mutation of
      exon 11 of c-kit were identified in 3 cases. During the follow up ranging from 9
      to 80 months, all the 7 patients had cancer-free survival. CONCLUSION: The
      biological behavior of cystic GIST is indolent with a low risk of malignancy and
      favorable prognosis.

PMID- 21866452
TI  - [Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of
      the stomach: a clinical controlled study].
AB  - OBJECTIVE: To compare the surgical outcomes between laparoscopic and open wedge
      resection for gastrointestinal stromal tumors of the stomach. METHODS: Clinical
      data of 18 cases undergoing laparoscopic wedge resection from June 2000 to August
      2009 at the Zhejiang Provincial People's Hospital were compared with 30 patients
      treated by open surgery. The perioperative parameters and prognosis data of the
      two groups were compared. RESULTS: Compared to the open group, laparoscopic group
      was found with longer operative time, less blood loss, less requirement of
      postoperative analgesia, earlier resumption of oral intake, earlier return of
      first flatus, and shorter postoperative hospital stay(all P<0.05). There were no
      postoperative deaths in both groups. Postoperative complication rate was
      significantly lower in the laparoscopic group(5.5% vs. 33.3%, P<0.05). The
      postoperative recurrence rates were 11.8%(2/17) and 10.7%(3/28); the 5-year
      survival rates were 78% and 63%, respectively, and the difference was not
      statistically significant(P>0.05). CONCLUSION: Laparoscopic wedge resection is a
      feasible treatment option for GISTs of the stomach.

PMID- 21866453
TI  - [Meta-analysis of randomized controlled trials comparing laparoscopic with open
      surgery for rectal cancer on oncologic clearance and long-term oncologic
      outcomes].
AB  - OBJECTIVE: To compare oncologic adequacy of resection and long-term oncologic
      outcomes between laparoscopic-assisted surgery (LS) and open surgery (OS) in the
      treatment of rectal cancer. METHODS: Literature searches of electronic databases
      (PubMed, Embase, Web of Science,and Cochrane Library) and manual searches up to
      June 30, 2010 were performed to identify RCTs comparing values of oncologic
      adequacy of resection, recurrence and survival following LS and OS. Fixed and
      random effects models were used. RESULTS: Six RCTs enrolling 1033 participants
      (LS group:577 cases, OS group:456 cases)were included in the meta-analysis.
      Number of lymph node harvested was similar(WMD=-0.38, 95%CI:-1.35-0.58, P=0.43).
      LS had a slightly higher circumference resection margin(CRM) positive rate with
      no statistical significance[7.94% vs. 5.37%; risk ratio(RR)=1.13; 95%CI:0.69
      1.85, P=0.63]. There was no significant difference between the two groups in
      local recurrence (RR=0.55; 95%CI:0.22-1.40, P=0.21). The 3-year overall survival
      [Hazard ratio(HR)=0.76; 95%CI:0.54-1.07, P=0.11] and 3-year disease-free
      survival(HR=1.16; 95%CI:0.61-2.20, P=0.64) were not significantly different
      between the two groups. CONCLUSION: Compared with open surgery, laparoscopic
      surgery of rectal carcinoma offers similar oncological clearance and long-term
      oncological outcomes.

PMID- 21866454
TI  - [Totally laparoscopic Billroth II( gastrectomy without intracorporeal hand-sewn
      sutures].
AB  - OBJECTIVE: To evaluate the safety and feasibility of a novel totally laparoscopic
      Billroth II gastrectomy. METHODS: Twelve gastric cancer patients underwent
      totally laparoscopic D2 dissection without intracorporeal hand-sewn sutures in
      the Xijing Hospital of Fourth Military Medical University between May 2011 and
      July 2011. In this technique, circular stapling device was used for
      gastrojejunostomy, and an Endo GIA was used to close the incision at the greater
      curvature of the stomach. After the completion of the anastomosis, a side-to-side
      anastomosis (jejunum-afferent loop or jejunum-efferent loop) was performed using
      an Endo-GIA. RESULTS: No patients required conversion to laparoscopy-assisted or
      open surgery. The operative time was 196.0+/-19.3 min, and the blood loss was
      169.5+/-28.8 ml. The number of lymph node harvested was 25.1+/-3.3. The proximal
      resection margin and distal resection margin were 8.8+/-2.4 cm and 6.9+/-5.5 cm,
      respectively. The mean time to the first postoperative flatus was 3.1+/-1.3 days.
      The length of hospital stay was 4.5+/-1.9 days. CONCLUSION: This technique is
      simple and quick. There is no need for laparoscopic hand-sewn suturing. It is
      safe to perform for totally laparoscopic gastrectomy and reconstruction.

PMID- 21866455
TI  - [Analysis of 61 cases undergoing sphincter-preserving procedure with
      intersphincteric resection by telescopic anastomosis for ultra-low rectal
      cancer].
AB  - OBJECTIVE: To investigate the efficacy and safety of sphincter-preserving
      procedure with transabdominal intersphincteric resection for ultra-low rectal
      cancer. METHODS: Clinical data of 61 cases with ultra-low rectal cancer (distance
      from anal verge ranged from 4-5 cm) were analyzed retrospectively. The patients
      underwent sphincter-preserving procedure with intersphincteric resection and
      telescopic anastomosis. RESULTS: There were 34 males and 27 females. The mean age
      was 56.7 years. The inferior border of the tumor was 4 cm above the anal verge in
      21 cases, and 5 cm in 40 cases. There 55 patients with rectal adenocarcinoma in
      this cohort. The tumor was well-differentiated in 24 cases, moderately
      differentiated in 29 cases, and poorly-differentiated in 2 cases. There were 6
      cases with malignant adenoma. The TNM staging was T1N0M0 in 36 cases, T2N0M0 in
      23, and T3N1M0 in 2. The ability to control defecation significantly improved in
      1-3 months postoperatively, and returned to normal in 6-12 months. Two patients
      developed anastomotic leak (3.3%), and 3 anastomotic stenosis (4.9%)
      postoperatively. Fifty-four patients(88.5%) had follow-up. The median follow-up
      time was 6.2 years. The local recurrence rate was 5.6%, and the 5-year-survival
      rate was 73.5%. CONCLUSION: Sphincter-preserving procedure with intersphincteric
      resection and telescopic anastomosis is a safe and effective procedure for ultra
      low rectal cancer.

PMID- 21866456
TI  - [Rectal non-Hodgkin lymphoma with concomitant rectal adenocarcinoma: a case
      report and literature review].
AB  - OBJECTIVE: To report a case of rectal non-Hodgkin lymphoma with concomitant
      rectal adenocarcinoma. METHODS: Clinical records of a 71 years old male patient
      with rectal non-Hodgkin lymphoma with concomitant rectal adenocarcinoma admitted
      on May 19, 2010 to the First Affiliated Hospital of Sun Yet-sen University were
      retrospectively reviewed. Clinical manifestations, diagnosis, and treatment as
      well as postoperative pathology were summarized. RESULTS: The preoperative
      diagnosis of the patient was severe atypical adenomatous hyperplasia with focal
      carcinogenesis, and the preoperative staging was T2N0-1M0. The patient underwent
      a Parks procedure (rectal resection and colo-anal anastomosis) and subtotal
      resection of left lateral liver. The operation was successful, postoperative
      recovery uneventful. Postoperative pathology showed moderately differentiated
      tubular adenocarcinoma with deep muscular invasion, and non-Hodgkin lymphoma with
      marginal zone cell. Both the distal and proximal resection margins were negative
      and no vascular and neural invasion were seen. Immunohistochemical staining
      indicated L26(+), Bcl-2(+), Bcl-6(+), CD3(-), CD23(-), CK epithelial cells(+),
      and M-CEA luminal border(+). The pathological and immunohistochemistry results of
      liver specimens showed hepatic mucosa-associated marginal zone lymphoma.
      CONCLUSIONS: Rectal adenocarcinoma and lymphoma occurring at the same site
      simultaneously is extremely rare with unique pathologic features.

PMID- 21866457
TI  - [Surgical treatment and prognostic factors for obstructing left colorectal
      cancer].
AB  - OBJECTIVE: To investigate the outcomes of surgical treatment and the prognostic
      factors of long-term survival for obstructing left colorectal cancer. METHODS:
      Clinicopathological and follow-up data of 93 patients with obstructing left
      colorectal cancer undergoing surgical treatment from January 2001 to December
      2006 in the Affiliated Hospital of Medical College of Qingdao University were
      analyzed retrospectively. RESULTS: There were 53 males and 40 females. The median
      age was 61 years old. Fifty-one patients had concurrent medical condition.
      Radical resection was performed in 67 patients, including one-stage resection
      (n=21), Hartmann procedure (n=35), and Miles procedure (n=11). Surgery was
      palliative in 26 patients, including diverting stoma (n=14), bypass surgery
      (n=7), and palliative resection (n=5). All the 93 patients were followed up. The
      1-, 3-, and 5-year survival rates were 94%, 59%, and 38%, respectively.
      Univariate and multivariate analyses showed that radical resection, TNM staging,
      and preoperative level of carcinoembryonic antigen were independent prognostic
      factors (all P<0.05). CONCLUSIONS: Radical resection, TNM stage, and preoperative
      CEA level are prognostic factors of obstructing left colorectal cancer. Early
      diagnosis, radical resection, and selection of appropriate surgical procedure are
      helpful to prolong survival time of patients with obstructing left colorectal
      cancer.

PMID- 21866458
TI  - [Mechanism of polycomb Bmi1-targeted therapy for colorectal cancer].
AB  - OBJECTIVE: To investigate the Bmi1 protein level in human colorectal cancer
      specimen and associated clinicopathological parameters, and to determine the
      influence of Bmi1 on the proliferation and apoptosis of colorectal cancer cells.
      METHODS: Bmi1 protein level was assessed in 85 patients with colorectal cancer
      and adjacent normal tissue by immunohistochemistry. SW480 cells were transfected
      with Bmi siRNA plasmid. MTT assay and flow cytometry were used to measure the
      proliferation and apoptosis of SW480 cells. The expression of Bmi1 and Bcl-2 were
      measured by Western blot. RESULTS: The positive rate of Bmi1 expression in
      colorectal cancer tissues was 56.5%(48/85), significantly higher than that in the
      adjacent noncancerous tissues[17.6%(15/85), P<0.05)]. It was found that the
      overexpression of Bmi1 was associated with degree of differentiation, status of
      lymph nodes metastasis, and TNM staging in colorectal cancer(P<0.05). After
      transfection of SW480 with Bmi1 siRNA, the cell proliferation was inhibited and
      the apoptosis was significant. The cell proliferation inhibitory rates were
      13.1%, 16.5%, and 18.3% at 24 h, 48 h and 72 h after transfection. The apoptotic
      rates were 15.7%, 45.6%, 40.2%, respectively. Expression of Bmi1 was
      downregulated after 48 h, as was that of Bcl-2. CONCLUSIONS: Bmi1 expression is
      associated with the clinicopathological characteristics of colorectal cancer.
      Blockade of Bmi1 can inhibit the proliferation and accelerate the apoptosis of
      colorectal cancer cells.

PMID- 21866459
TI  - [Preliminary study on relationship between multi-drug resistance-associated
      protein 4 and radiosensitivity of rectal cancer].
AB  - OBJECTIVE: To explore the correlation between multi-drug resistance-associated
      protein 4(MRP4) and the sensitivity of rectal cancer to radiation. METHODS: A
      total of 95 patients with advanced rectal cancer and received radiation therapy
      between January 2000 and January 2009. MRP4 and P53 protein expression in the
      paraffin-embedded specimen were detected by immunohistochemistry. Logistic
      regression analysis was used to evaluate factors associated with the sensitivity
      of rectal cancer to radiation. RESULTS: Forty patients(42%) were sensitive to
      radiation therapy, of whom 10(11%) achieved pathological complete remission.
      Fifty-five patients were (58%) not responsive to radiation. Patients with low
      expression of MRP4 had a 66.7%(24/36) response rate, significantly higher than
      that of patients with high MRP4 expression (29.1%,16/59)(P<0.05). Patients with
      low expression of P53 had a 63.9%(23/36) response rate, significantly higher than
      that of patients with high P53 expression(28.8%,17/59)(P<0.01). The response rate
      after long course radiation therapy was 83.3%(20/24), significantly higher than
      that of patients who underwent short and medium course radiation[(31.3%, 5/16)
      and(27.3%,15/55)](P<0.01). Multivariate Logistic regression analysis showed
      radiation regimen, the expression of P53 and MRP4 protein were independently
      associated with the sensitivity of rectal cancer to radiation(P<0.05).
      CONCLUSION: MRP4 may serve as a predictive marker for the sensitivity of rectal
      cancer to preoperative radiation.

PMID- 21866460
TI  - [(-)-Epigallocatechin-3-gallate reduces vascular endothelial growth factor
      expression in gastric cancer cells via suppressing activity].
AB  - OBJECTIVE: To investigate the molecular mechanism involved in the downregulation
      of vascular endothelial growth factor(VEGF) expression through the suppression of
      signal transducer and activator of transcription 3(Stat3) by(-)-Epigallocatechin
      3-gallate (EGCG). METHODS: After human gastric cancer cells (AGS) were treated
      with IL-6 (50 MUg/L) and EGCG(0, 5, 10, 25 or 50 MUmol/L), the expression levels
      of VEGF, total Stat3(tStat3), and activated Stat3(pStat3) in tumor cells were
      examined by Western blotting. The influence of the inhibitor of Stat3 pathway on
      the IL-6-induced VEGF expression was investigated. VEGF protein level in tumor
      cell culture medium was determined by ELISA and VEGF mRNA expression in tumor
      cells by RT-PCR. Tumor cell nuclear extract was prepared and nuclear expression
      of pStat3 was detected. Stat3-DNA binding activity was examined with chromatin
      immunoprecipitation (ChIP) assay. RESULTS: IL-6 significantly increased VEGF
      expression in AGS gastric cancer cells. Compared with the group without IL-6, the
      expression and secretion of VEGF protein, and mRNA expression increased by 2.4
      fold,2.8 fold, and 3.1 fold(all P<0.01), respectively. EGCG treatment markedly
      reduced VEGF protein, release and mRNA expression in a dose-dependent manner.
      When compared with the control group induced by IL-6, EGCG and AG490(a Stat3
      pathway inhibitor) significantly inhibited VEGF expression induced by IL-6
      (P<0.01). EGCG dose-dependently inhibited pStat3 induced by IL-6(P<0.05), but not
      tStat3 (P>0.05). Stat3 nuclear translocation and Stat3-DNA binding activity in
      AGS cells or that induced by IL-6 were directly inhibited by EGCG(P<0.05).
      CONCLUSION: EGCG reduces expression of VEGF in gastric cancer cells through the
      inhibition of Stat3 activity.

PMID- 21866461
TI  - [Inhibitory effect and mechanism of (-)-epigallocatechin-3-gallate on HT29 and
      HCT-8 colorectal cancer cell lines and expression of HES1 and JAG1].
AB  - OBJECTIVE: To study the inhibitory effect of (-)-epigallocatechin-3-gallate
      (EGCG) on cancer cells line HCT-8 and HT29 and its influence on the expression of
      HES1 and JAG1. METHODS: Colorectal cancer cells line HCT-8 and HT29 were cultured
      in vitro and treated with different concentrations of EGCG(10 mg/L, 20 mg/L, 35
      mg/L). The inhibition of proliferation was tested by MTT analysis. Influence of
      EGCG on the cell apoptosis and cell cycle of HCT-8 and HT29 were detected with
      flow cytometry, and gene expression of HCT-8 and HT29 after EGCG treatment with
      real-time polymerase chain reaction. RESULTS: EGCG affected the proliferation and
      apoptosis of HCT-8 and HT29. The inhibition rates of the three different
      concentrations of EGCG were(28.894+/-5.076)%, (34.903+/-1.794)%, and (39.028+/
      0.105)% on HCT-8, and (14.682+/-4.244)%, (22.429+/-3.847)%, and (29.840+/-5.076)%
      on HT29. EGCG caused G(2)/M phase arrest and M phase transition in HCT-8 cell
      line, and S phase arrest and G2 phase transition in HT29 cell line. EGCG down
      regulated HES1 gene expression in both cell lines, however, the differences were
      not statistically significant(both P>0.05). EGCG upregulated JAG1 gene expression
      in both cell lines, however only the difference in HCT-8 was statistically
      significant(0.201+/-0.018 vs. 0.440+/-0.077, P=0.029). CONCLUSIONS: EGCG can
      significantly inhibit the proliferation of HT29 cells and HCT-8 cells by changing
      cell cycle and inducing cell apoptosis. The mechanism may be related to the
      upregulation of JAG1 gene expression.

PMID- 21866462
TI  - Reed-Sternberg cells in classical Hodgkin lymphoma in children seem to be
      predominantly oestrogen receptor alpha negative and oestrogen receptor beta
      positive.
AB  - Oestrogen receptor alpha (ERalpha) is responsible for activation of gene
      transcription, while oestrogen receptor beta (ERbeta) serves as a negative
      regulator of ERalpha function. Since ER status is a prognostic and predictive
      factor in some cancers, we analysed the immunohistochemical expression of ERalpha
      and ERbeta in Reed-Sternberg (RS) cells in paraffin-embedded lymph node specimens
      from 27 children with classical Hodgkin lymphoma (HL) in relation to histological
      type, clinical stage, age, and gender. Percentage of RS cells with positive
      nuclear reaction for the presence of ERalpha and/or ERbeta was assessed. ERalpha
      positive RS cells were present in 11% (3/27) of lymph nodes (range 1-8%, mean
      0.4%) whereas ERbeta positive RS cells were detected in 96% (26/27) of lymph
      nodes (range 1-97.5%, mean 61.8%). The highest percentage of ERbeta positive RS
      cells was observed in patients with the most advanced (IVB) disease as compared
      to patients with lower stages (90.3% vs. 56.9% respectively, p = 0.004). To the
      best of our knowledge this is the first report on the expression of ERbeta in RS
      cells in children. We conclude that RS cells in classical HL in children seem to
      be mainly ERbeta positive and ERalpha negative.

PMID- 21866463
TI  - Minichromosome maintenance 2 (MCM2) is a new prognostic proliferative marker in
      Wilms tumour.
AB  - OBJECTIVE: We examined expression of minichromosome maintenance 2 (MCM2) by
      immunohistochemistry in nephrectomy specimens of children with nephroblastoma
      treated according to the Society International d'Oncologie Pediatrique (SIOP)
      scheme to determine its potential prognostic significance. MATERIAL AND METHODS:
      18 children with nephroblastoma, 9 females and 9 males, 2 months to 7 years of
      age, treated in the Department of Oncology and Paediatric Surgery, Medical
      University of Lodz, during the period 1994-2006 were analysed. Children were
      treated by neoadjuvant chemotherapy and subsequent nephrectomy according to SIOP
      protocols -93 and 2001 and followed up from 2 to 11 years. The tumour stage and
      classification in nephrectomy specimens were established according to the revised
      2001 SIOP working classification of renal tumours of childhood. RESULTS: In low
      risk nephroblastoma MCM2 expression was low, ranging from 0% in two cases of
      completely necrotic nephroblastoma to 5% in one child with cystic partially
      differentiated nephroblastoma. In mesoblastic nephroma, which is a distinct type
      of neoplasm with a low malignant potential and the most common congenital renal
      neoplasm, MCM2 expression was variable ranging from 2-5% in 2 children with stage
      I disease to 70% in one child with stage III disease In intermediate risk
      nephroblastoma MCM2 expression was low (10%) in one case of regressive type
      nephroblastoma and stage II disease and intermediate to high in children with
      epithelial type nephroblastoma, ranging from 40-50% in one case with stage I
      disease to 70% and 70-100% in 2 children with stage I and stage IV disease,
      respectively. In high risk nephroblastoma (7 children with nephroblastoma
      blastemal type) MCM2 expression was intermediate to high, ranging from 40 to 90%.
      MCM2 expression tends to be lower in children with less advanced stage of disease
      (stage II) and higher in more advanced disease (stage III and IV). Two children
      with blastemal type and high (> 60% MCM2) died of disease within 2-4 years from
      diagnosis and one child was lost to follow-up. Both children who died were older
      8.5 yo M and 7 yo M and presented with advanced disease stage IV or III with
      anaplasia. CONCLUSION: MCM2 is a promising prognostic factor in WT treated
      according to the SIOP scheme.

PMID- 21866464
TI  - Single nucleotide polymorphism in DNA base excision repair genes XRCC1 and hOGG1
      and the risk of endometrial carcinoma in the Polish population.
AB  - BACKGROUND: Polymorphisms in the human oxoguanine glycosylase 1 ( hOGG1 ) and X
      ray repair cross-complementing 1 ( XRCC1 ) genes have been extensively studied in
      the association with various human cancers such as endometrial cancer. MATERIAL
      AND METHODS: The genotype analysis of hOGG1 Ser326Cys and XRCC1 Arg399Gln gene
      polymorphisms for 150 endometrial cancer patients and 150 controls of cancer-free
      subjects, in the Polish population, were performed using PCR-based restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: Although there were no
      significant (p > 0.05) differences in the frequencies of genotypes or alleles of
      hOGG1 genes between patients and controls, the frequency of the XRCC1 399Gln
      allele was significantly greater in endometrial cancer patients compared with
      controls (p = 0.033) with an odds ratio of 1.39 (95% confidence interval 0.99 to
      1.95). The distributions of genotypes and alleles of the genes hOGG1 and XRCC1
      were not significantly associated with different grades of endometrial cancer (p
      > 0.05). CONCLUSION: In conclusion, these findings indicated that XRCC1 Arg399Gln
      polymorphism may be a genetic determinant for developing endometrial cancer. The
      hOGG1 Ser326Cys may not play an important role in susceptibility to endometrial
      cancer in Polish women.

PMID- 21866465
TI  - Accuracy of immunohistochemistry in evaluation of malignant pleural and
      peritoneal effusions.
AB  - BACKGROUND: The aim was to evaluate the accuracy of immunohistochemistry in
      diagnosis of the source of malignancies in pleural and peritoneal fluids in
      comparison to histopathology as the gold standard. MATERIAL AND METHODS:
      Retrospectively, the cell block specimen and past medical data files of patients
      who had undergone serosal fluid aspiration and had a histopathology report
      corresponding to underlying disease were retrieved. Three mesothelial antibodies
      (D2-40, calretinin and WT-1) and two non-mesothelial antibodies (MOC-31 and EMA)
      were set to be applied for evaluating malignant cells and benign cells within
      serous fluids. RESULTS: Seventy-one patients, 12 men and 59 women, were found to
      have a thorough information package needed, including cell blocks with
      appropriate cellularity on which ICC was applicable and the corresponding
      histopathology report. As mesothelial markers, calretinin and WT-1 were found to
      have sensitivity and specificity of 90%, 96.7% and 100%, 42.6%, respectively.
      Sensitivity and specificity of D2-40 both reached 100%. In addition, as non
      mesothelial markers, MOC-31 and EMA were demonstrated to have sensitivity and
      specificity of 95.08%, 90% and 93.4%, 70%, respectively. CONCLUSION: D2-40 was
      reconfirmed to act as an accurate marker in distinguishing between cells of
      mesothelial and non-mesothelial origin. However, WT-1 is not specific enough to
      be considered as accurate as D2-40. Considering the sensitivity and specificity
      of calretinin and MOC-31, they can be considered as safe but not as much as D2
      40. EMA is not recommended as an ancillary marker due to its low specificity and
      challenging results.

PMID- 21866466
TI  - Systemic mastocytosis (SM) and associated malignant bone marrow histiocytosis - a
      hitherto undescribed form of SM-AHNMD.
AB  - An elderly woman presented with anaemia, thrombocytopenia and multifocal lytic
      and sclerotic bone lesions. Trephine bone marrow biopsy demonstrated widespread
      involvement by systemic mastocytosis (SM). The neoplastic mast cells expressed
      mast cell tryptase, CD117, CD25 and CD9, and were accompanied by compact sheets
      of atypical large histiocytic cells, expressing CD68, CD4, S-100 protein and
      CD14, in keeping with a concomitant histiocytosis (SM-AHNMD). Mutation analysis
      revealed the activating point mutation D816V of the c-kit proto-oncogene in
      microdissected pooled bone marrow mast cells. Partial remission was achieved
      using interferon alpha. To the best of our knowledge this is the first reported
      case of SM-AHNMD with histiocytosis as the non-mast cell component.

PMID- 21866467
TI  - Pulmonary acinic cell carcinoma (Fechner tumour) with carcinoid component. A case
      report.
AB  - The authors present a very rare case of primary lung acinic cell carcinoma with
      carcinoid component in a 53-year-old man.

PMID- 21866468
TI  - Mesenchymal hamartoma of the liver - case report and short literature overview.
AB  - Mesenchymal hamartoma (MH) is an uncommon benign hepatic tumour that presents
      mostly before the age of 2 years. Its biology and pathogenesis are poorly
      understood. We present the case of a 1-year-old male patient with a huge tumour
      of the right lobe of the liver which showed rapid enlargement. Imaging procedures
      revealed a central solid lesion, 18 cm in diameter in the right lobe of the
      liver, with cystic degeneration. After surgical resection a diagnosis of
      mesenchymal hamartoma was established by pathological examination of the surgical
      specimen. Postoperative recovery of the patient was uneventful.

PMID- 21866469
TI  - Peripheral intrapulmonary lipoma in a 26-year-old woman - a case report.
AB  - Rare in occurrence, the following case of intrapulmonary lipoma is only the fifth
      known case in a female patient reported in the literature. Importantly, the
      incorporation of this lesion into the differential diagnosis during frozen
      section of a predominantly adipocytic lesion limited the extent of surgical
      intervention and provided the patient with an optimal standard of care.

PMID- 21866470
TI  - A brief report of a rare case of giant apocrine hidrocystoma presenting as a
      scalp hematoma.
AB  - Apocrine hidrocystoma is a benign cystic tumour. The head and neck region is the
      site of predilection; occurrence in the scalp is extremely rare. We report a rare
      case of giant apocrine hidrocystoma with an unusual presentation as scalp
      haematoma.

PMID- 21866471
TI  - Clinical expression of autoimmune hepatitis in a nine-year-old girl with visceral
      leishmaniasis.
AB  - Autoimmune hepatitis (AIH) is a chronic disease of unknown aetiology, which
      usually progresses to cirrhosis if not diagnosed and treated promptly. In
      childhood, autoimmune hepatitis prevalently presents with non-specific
      indications. The cause of entrance to hospital of the 9-year-old child was fever
      for 6 days (39 degrees C) and intense cough, with other clinical symptoms and
      signs: abdominal distention, paleness, lack of appetite. In our case we report
      experience with AIH presenting with atypical clinical features of visceral
      leishmaniasis.

PMID- 21866472
TI  - A case of cutaneous bronchogenic cyst in the scapular area.
AB  - Cutaneous bronchogenic anomalies are rare. We report a 4-year-old boy who
      presented with a tumour and relapsing infection in the right scapular region.
      Histopathological examination of this tumour revealed a subcutaneous cystic
      legion formed by ciliated columnar epithelium with smooth muscle bundles and
      squamous epithelium with sebaceous glands.

PMID- 21866473
TI  - Benign multicystic peritoneal mesothelioma (BMPM) - case report and review of the
      literature.
AB  - Benign multicystic peritoneal mesothelioma (BMPM), also known as multilocular
      peritoneal inclusion cyst, is a rare tumour that occurs mainly in women at their
      reproductive age. The aetiology and pathogenesis are controversial. It originates
      from any abdominal peritoneal or pleural surface. The biological behaviour of
      BMPM is usually clinically benign. Here we present a case report of BMPM from our
      department with a review of the literature.

PMID- 21866474
TI  - Pyostomatitis vegetans: report of a rare case.
AB  - Pyostomatitis vegetans is a rare chronic disorder of the oral mucosa. It is a
      highly specific marker for inflammatory bowel disease. Although immunological and
      microbial factors have been suggested as predisposing factors, the exact
      aetiology is unknown. Here, a case of pyostomatitis vegetans in a 30-year-old
      woman is reported. No bowel involvement was observed. Report of such cases
      emphasizes the importance of early diagnosis of oral findings in control and
      management of disease.

PMID- 21866475
TI  - Correct answer to the quiz. Check your diagnosis: adenomatoid odontogenic tumour.

PMID- 21866478
TI  - Early and long-term results of the treatment of jugular paragangliomas using
      different ranges of surgical approach.
AB  - BACKGROUND AND PURPOSE: The applied approach to the jugular foramen is a
      combination of the juxtacondylar approach with the subtemporal fossa approach
      type A. The purpose of this study is to present our results of treatment of
      jugular paragangliomas using the aforementioned approach. MATERIAL AND METHODS:
      Twenty-one patients (15 women, 6 men) with jugular paragangliomas were included
      in the study. The neurological status of the patients was assessed before and
      after surgery as well as at the conclusion of treatment. The approximate volume
      of the tumour, its relation to large blood vessels, cranial nerves and brainstem,
      as well as consistency and vascularity were also assessed. RESULTS: The duration
      of symptoms ranged from 3 to 74 months. In 86% of patients hearing loss was the
      predominant symptom. The less frequent symptoms included pulsatile tinnitus in
      the head, dysphagia and dizziness. Approximate volume of the tumours ranged from
      2 to 109 cm3. A gross total resection was achieved in 71.5% of patients. The
      postoperative performance status improved in 38% of patients, did not change in
      38% and deteriorated in 24% of patients. CONCLUSIONS: A proper selection of the
      range of the approach to jugular foramen paragangliomas based on their topography
      and volume reduces perioperative injury without negative consequences for the
      radicality of the resection.

PMID- 21866477
TI  - Incidence and case fatality rates of first-ever stroke - comparison of data from
      two prospective population-based studies conducted in Warsaw.
AB  - BACKGROUND AND PURPOSE: According to official statistics, the stroke mortality
      rate has remained high in Eastern European countries for a few decades. It has
      been shown that also in Poland stroke mortality failed to decline in the period
      1984 to 1992. Since that time, stroke management in our country has changed,
      especially in the cities, where stroke units have been developed. The aim of the
      present study was to compare incidence and case fatality rates, estimated on the
      basis of two prospective population-based studies performed in Warsaw in
      1991/1992 and 2005. MATERIAL AND METHODS: Incidence rates and case fatality rates
      for the first-ever-in-a-lifetime stroke have been estimated on the basis of two
      population-based studies: the Warsaw Stroke Registry (population 182 649)
      conducted in 1991 and 1992, and the European Register of Stroke (population 120
      186) - registration in 2005. In both studies data were standardized to the
      European population by the direct methods. RESULTS: Contrary to the incidence
      rates, which did not change significantly between 1991/1992 and 2005, 30-day and
      1-year case fatality rates decreased significantly from 43% to 14.9% and from
      59.7% to 33.1%, respectively. CONCLUSIONS: Comparison of data from two population
      based prospective stroke registries showed that stroke case fatality and
      mortality significantly decreased. This may be associated with the better
      management of patients in the acute phase of stroke and implementation of
      secondary prevention strategies for stroke.

PMID- 21866479
TI  - Prospective study on the efficacy of low-field intraoperative magnetic resonance
      imaging in neurosurgical operations.
AB  - BACKGROUND AND PURPOSE: The application of intraoperative magnetic resonance
      imaging (iMRI) is related to a series of challenges of both a technical and an
      organizational nature. We present our experience in the application of low-field
      iMRI in everyday neurosurgical practice. MATERIAL AND METHODS: A group of 58
      patients operated on using low-field iMRI was subject to prospective controlled
      observation. The significance of differences in the range of preparation time,
      duration and direct operation results between the iMRI group and controls was
      analysed. The influence of epidemiological and demographic factors and technical
      aspects related to iMRI application on direct outcome of the surgery was
      assessed. RESULTS: Twenty-eight tumour resections using craniotomy, 17
      transsphenoidal resections of pituitary adenomas and 13 stereotactic procedures
      were conducted in the group of 24 men and 34 women operated on using iMRI. The
      control group was not significantly different in terms of epidemiological and
      demographic factors. The preparation and operation times were significantly
      longer in the iMRI group (p < 0.001 and p = 0.002, respectively). Longer duration
      of the surgery was not related to an increased frequency of complications. A
      higher percentage of postoperative improvement in neurological status (31% vs.
      14%, p = 0.045), lower complication percentage (10% vs. 28%, p = 0.03) and a
      similar time of hospitalization (13 +/- 7 vs. 12 +/- 4 days, p = 0.33) were noted
      in the iMRI group. CONCLUSIONS: The application of low-field iMRI prolongs the
      duration of neurosurgical procedures but does not negatively influence their
      safety. It is associated with above-average functional results and a lower
      percentage of total complications.

PMID- 21866480
TI  - Validation analysis of the Polish version of the Multiple Sclerosis International
      Quality of Life Questionnaire (MusiQoL).
AB  - BACKGROUND AND PURPOSE: The aim of this study was to perform a validation
      analysis of the Polish adaptation of the Multiple Sclerosis International Quality
      of Life Questionnaire, MusiQoL. MATERIAL AND METHODS: Validation analysis
      included the translation of the original English version into Polish according to
      translation principles and the analysis of convergent validity, internal
      reliability and reproducibility of the Polish version of MusiQoL. The study
      included 150 randomly chosen patients (109 women and 41 men) with definite
      multiple sclerosis (MS) diagnosed according to McDonald criteria. Mean age of
      patients was 41 +/- 10 years and mean disease duration was 11.7 +/- 7.2 years.
      The patients completed the examined MusiQoL, the Functional Assessment of
      Multiple Sclerosis (FAMS) and the Multiple Sclerosis Impact Scale (MSIS-29). Data
      regarding sociodemographic status and MS history were collected. The disability
      of the patients was assessed according to the Expanded Disability Status Scale
      (EDSS). The examination was repeated after 28 +/- 4 days. RESULTS: The internal
      reliability, convergent validity and reproducibility of MusiQoL were
      satisfactory. The dimensions of the scale exhibited high internal consistency
      (Cronbach's alpha from 0.67 to 0.90). The MusiQoL correlated with FAMS (positive
      correlations), EDSS and MSIS-29 (negatively). CONCLUSIONS: Psychometric
      statistical analysis showed that the Polish version of MusiQoL is a valuable
      measure to examine the health-related quality of life of Polish MS patients.

PMID- 21866481
TI  - Development of early comprehensive stroke inpatient rehabilitation in Poland -
      current status and future requirements.
AB  - BACKGROUND AND PURPOSE: Every stroke patient should undergo early rehabilitation.
      We aimed to evaluate accessibility, development and needs in early stroke
      inpatient rehabilitation in Poland. MATERIAL AND METHODS: A questionnaire
      evaluating rehabilitation departments was prepared and sent (in 2004 and 2008) to
      rehabilitation wards in Poland, where stroke patients are treated and undergo
      early rehabilitation. We divided departments into classes: class A - having
      comprehensive rehabilitation (physiotherapy minimum 60 minutes/day, speech
      therapy minimum 30 minutes/5 days/week, rehabilitation of other cognitive
      impairments minimum 30 minutes/5 days/week, group physiotherapy); B - having the
      possibility of all types of therapy, but done less frequently; C - physiotherapy
      and speech therapy; D - physiotherapy and cognitive rehabilitation; E - only
      physiotherapy. RESULTS: In 2004, we obtained responses from 115 of 172 (66.9%)
      rehabilitation departments. According to prespecified criteria there were 11
      class A, 31 class B, 28 class C, 4 class D, and 41 class E wards. In 2008, we
      received response from 89 of 149 (59.7%) rehabilitation departments. According to
      prespecified criteria there were 17 class A, 40 class B, 22 class C, 0 class D,
      and 10 class E wards. In 2004, 159 beds and in 2008, 294 beds in class A
      departments were available for stroke patients. The minimal number of needed but
      lacking beds was 604 in 2004 and 469 in 2008. CONCLUSIONS: Development of
      departments providing early comprehensive stroke rehabilitation from 2004 to 2008
      is marked, but still insufficient. In 2008, 19% of rehabilitation departments
      could provide comprehensive stroke rehabilitation and this was 38.5% of beds
      actually needed.

PMID- 21866482
TI  - Chronic bilateral pallidal stimulation in patients with generalized primary
      dystonia - multi-contact cathodal stimulation is superior to bipolar stimulation
      mode. Preliminary results.
AB  - BACKGROUND AND PURPOSE: Primary generalized dystonia (PGD) is a medically
      refractory progressive disease of the brain causing near total handicap of
      affected patients. The aim of the study was to assess the efficacy and safety of
      bilateral pallidal stimulation in patients with PGD. MATERIAL AND METHODS: The
      study population is composed of 5 patients with PGD. The formal objective
      assessment included the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). All
      stereotactic procedures were performed in general anaesthesia using a Leksell G
      stereotactic head frame without electrophysiological guidance. Immediately after
      insertion of deep brain stimulation (DBS) leads, the internal pulse generators
      (Itrel II or Soletra) were implanted subcutaneously in the chest wall or
      abdominal region. RESULTS: There were no complications related to the
      stereotactic procedures. The hardware-related complications (two broken DBS
      leads) were replaced successfully. There were no infections or erosions of
      implanted hardware. It has been observed that in the long-term follow-up period
      primary set bipolar stimulation mode lost its benefit achieved previously.
      Various stimulation combinations were investigated. Monopolar cathodal or
      especially multi-contact cathodal stimulation was the most effective one. The
      efficacy of bilateral pallidal stimulation was proved by the objective validated
      BFMDRS at long-term follow-up. CONCLUSIONS: Response to DBS may improve with the
      number of activated cathodal contacts within the globus pallidus internus.

PMID- 21866483
TI  - [Approach to the jugular foramen and related structures - an analysis of the
      surgical technique based on cadaver simulation].
AB  - This study presents consecutive stages of the approach to the jugular foramen and
      related structures. Eleven simulations of the approach were performed on non
      fixed human cadavers without any known pathologies in the head and neck. The
      consecutive stages of the procedure were documented with photographs and
      schematic diagrams. The starting point for the discussed approach is removal of
      the mastoid and petrosal parts of the temporal bone, as well as the jugular
      process and the jugular tuberculum. It allows penetration of the jugular foramen
      from the back. Widening of the approach enables penetration of the jugular
      foramen from above and the front. Approach to the jugular foramen is a
      reproducible technique, which provides surgical penetration of this foramen and
      related structures. This approach is particularly useful in the surgical
      treatment of tumours expanding in the petrous pyramid, surroundings of the
      petrosal part of the internal carotid artery, cerebellopontine angle, subtemporal
      fossa and nervous-vascular bundle of the neck.

PMID- 21866484
TI  - [Epilepsy and pro-inflammatory cytokines. Immunomodulating properties of
      antiepileptic drugs].
AB  - Epilepsy is a complex and multifactorial phenomenon. Accumulating evidence
      suggests that the immune system may play an important role in neuronal
      excitability and epileptogenesis. In many animal models of epilepsy, seizures
      induced chemically or electrically cause glial activation and increased
      expression of pro-inflammatory cytokines (IL-1 beta, TNF- alpha, IL-6). The
      studies show that the IL-1 beta /IL-1Ra system may modulate epileptic activity
      and contribute to neuronal excitability. Exogenous IL-1 beta has pro-convulsive
      properties. The action of TNF- alpha and IL-6 is complex (either stimulating or
      inhibitory action of these cytokines on seizures, depending on their
      concentration and the type of receptors involved in the response). In vitro and
      in vivo experiments show that antiepileptic drugs could affect cytokine levels
      (e.g. valproate significantly inhibited production of TNF- alpha and IL-6 by
      human monocytic leukaemia cells). In epilepsy patients studies (including ex
      vivo) show elevated levels of IL-1 beta, IL-2, IL-5, IL-6 or TNF- alpha after
      carbamazepine, valproic acid and phenytoin. This review surveys the current state
      of knowledge regarding effects of pro-inflammatory cytokines on seizure
      pathogenesis. Cytokine modulatory actions of some antiepileptic drugs are also
      discussed.

PMID- 21866485
TI  - [Sonographic diagnosis and endovascular recanalization of the internal carotid
      artery in a patient with carotid thromboembolism following coiling of cerebral
      aneurysm].
AB  - Thromboembolism after brain aneurysm embolization involves high
      morbidity/mortality and its conservative treatment is still a standard policy. We
      report the practical utility of transcranial colour-coded Doppler sonography
      (TCCS) in the early diagnosis and effectiveness of prompt intravascular
      intervention in the treatment of this condition. A 50-year-old woman developed
      acute neurological deficit after intravascular re-embolization of a brain
      aneurysm. Severely decreased blood flow velocity in the middle cerebral artery
      was revealed with TCCS and angiography confirmed nearly complete occlusion of the
      carotid artery. After heparin administration, intravascular thrombectomy was
      performed at the same session with implantation of a stent. The symptoms faded
      away within hours and the patient recovered fully. Prompt intravascular
      intervention could be a valuable and efficient alternative in the treatment of
      thromboembolism after embolization of cerebral aneurysm. TCCS enables early
      differential diagnosis of this potentially devastating sequel.

PMID- 21866486
TI  - Preoperative embolization of a cerebellar haemangioblastoma using Onyx: case
      report and literature review.
AB  - Haemangioblastoma is a slow-growing, highly vascular tumour and typically occurs
      in the cerebellum but can also occur in the brainstem and spinal cord. Because of
      their hypervascularity and location, cerebellar haemangioblastomas can be
      difficult to remove. The purpose of preoperative embolization of
      haemangioblastomas is to decrease the intraoperative blood loss and to facilitate
      excision. However, the safety and efficacy of this procedure remain
      controversial. Here, we report the case of a man with cerebellar
      haemangioblastoma who underwent preoperative embolization with Onyx. The tumour
      was completely removed with minimal tumour bleeding. There was no complication
      related to embolization.

PMID- 21866487
TI  - Total ocular akinesis: Miller Fisher or Guillain-Barre syndrome?
AB  - Total, bilateral ophthalmoplegia is very rare. More than 50% of cases are Miller
      Fisher (MFS) and Guillain-Barre (GBS) syndromes. There is a correlation of MFS
      with anti-GQ1b antibodies. High levels of GQ1b gangliosides are found in myelin
      sheathes of cranial nerves supplying the extraocular muscles. This may explain
      the association of anti-GQ1b antibodies with ophthalmoplegia. Anti-GQ1b were also
      found in cases of GBS accompanied by ophthalmoplegia, atypical MFS (MFS without
      ataxia), MFS/GBS overlap syndromes and Bickerstaff brainstem encephalitis. This
      has led some authors to classify them as 'anti-GQ1b syndromes'. In this article
      we describe a diagnostically difficult case of a patient with a very rare, total
      bilateral paralysis of all ocular muscles, accompanied by bilateral ptosis,
      diminished tendon reflexes of upper extremities, paresis and hypoesthesia of the
      left upper extremity.

PMID- 21866489
TI  - Which is the best radiological technique to demonstrate spontaneous or endoscopic
      third ventriculostomy?

PMID- 21866491
TI  - [Special training therapy to reduce inflammation in Anti-Jo-1 syndrome].
AB  - A 46-year-old patient was frequently seen with a medically treated Anti-Jo-1
      syndrome. The patient had already been treated with azathioprine and oral
      corticosteroids on account of decreasing lung function, dyspnoea, fatigue, and
      beginning signs of myositis. Although high doses of steroids and azathioprine
      were administered, the muscleskeletal syndromes increased steadily. The patient
      used to be an active long-distance runner (20 km), but now was unable to perform
      that kind of physical exercise. It was decided to start a treatment with the
      GalileoTM training device for active muscle training of the lower extremities.
      Before and after three months of training the following assessment was performed:
      measurement of health-related quality of life (St. Georges respiratory
      questionnaire, SGRQ), ultrasound measurement of the cross-sectional area of the
      quadriceps muscle, 6 minute walk test (6 MWT), lung function testing, and
      assessment of serum markers of inflammation (TNF-alpha, interleukin-8, CRP, CK,
      myoglobin). After only two months, training with the GalileoTM five times a week
      has improved the patient's conditions dramatically. The training will be
      continued.

PMID- 21866490
TI  - ["Common variable immunodeficiency"--first diagnosis of a rare pneumological
      disease].
AB  - Common variable immunodeficiency (CVID) is generally used synonymously with "late
      onset hypogammaglobulinaemia", which is already indicative of the central
      pathological finding. Patients with CVID produce specifically less
      immunoglobulins, thus reducing their immunological competence. Our patient showed
      the typical medical history of undetected CVID. After excluding differential
      pneumological diseases, the suspected diagnosis was confirmed. This case report
      examines the complex of CVID as a cause for recurrent pneumological infections.
      It is the most prevalent form of severe antibody deficiency in children and
      adults and occurs with a probability of 1:25,000 in the population.

PMID- 21866492
TI  - [IBD ahead 2010--Answering important questions in Crohn's disease treatment].
AB  - The treatment of patients with inflammatory bowel disease has become more complex
      in recent years through the introduction of various immunosuppressive agents as
      well as the approval of monoclonal antibodies against TNF-alpha and patients
      receiving such treatment must be carefully monitored. National and international
      guidelines define a diagnostic and therapeutic context for the practitioner, but
      can only partially respond to specific questions on the procedure for individual
      patients. Within the framework of a project initiated by Abbott entitled "IBD
      ahead" 38 German IBD experts have elaborated concrete proposals for dealing with
      corticosteroids, immunosuppressants and TNF-alpha antibodies on the basis of the
      published literature and their own personal experience in order to close the gap
      between these guidelines and daily clinical practice. Statements were developed
      on the choice of correct timing of initiation, dose and duration of the
      individual substances and on how to proceed with patients exhibiting treatment
      failure. Moreover, recommendations are also made on drug combination strategies,
      safety monitoring and the risks regarding the development of infectious
      complications and malignancies. These recommendations are illustrated by case
      studies from everyday practice in participating centres.

PMID- 21866493
TI  - [Updated German guideline on diagnosis and treatment of ulcerative colitis,
      2011].

PMID- 21866494
TI  - [Alcohol and drug misuse of the elderly in health care facilities].
AB  - OBJECTIVE: A nationwide representative survey was conducted in residential care
      facilities and facilities offering care for the elderly in their homes (home care
      facilities) with the aim to estimate the rate of alcohol and drug misuse among
      this population and to evaluate the way in which nursing staff deal with the
      problem. METHOD: A total of 5000 randomly selected facilities were contacted with
      a 2-page questionnaire. Reliable data were obtained from 550 residential care
      facilities and from 436 home care facilities. RESULTS: According to the
      investigated facilities, the mean rate of misuse among the elderly was 14%.
      Nearly all facilities acknowledge the necessity to react to these facts, but only
      a quarter of them considered their staff to be sufficiently trained. 38.4% of the
      residential care facilities and 26.9% of the home care facilities have a concept
      on how to react to misuse problems. Addiction services are rarely contacted.
      CONCLUSIONS: The prevalence of alcohol and drug misuse among the elderly in
      health care facilities is high compared to the same age cohort of the total
      population. The lack of networking between facilities for the elderly and
      addiction services is remarkable.

PMID- 21866495
TI  - [Tuberculosis outbreak in 13 people in Saxony-Anhalt: indications of an infection
      chain by spoligotyping].
AB  - BACKGROUND: In Germany the number of new tuberculosis incidents continues to
      decline slightly. Cases of illnesses are often diagnosed late, due to the
      uncharacteristic course of tuberculosis. The success in environment
      investigations by health authorities in finding incidents within one infection
      chain depends on the compliance of patients among other factors. Tuberculosis
      occurs especially in groups with social disadvantages. In this population segment
      the identification of contact persons of a patient with infectious tuberculosis
      presents difficulties. Moreover, identifying the source of infection is
      frequently not successful. For these reasons, additional infections and
      sicknesses are caused. The cultural pathogen proof, including type
      differentiation and resistance testing, continues to be the "gold standard" in
      tuberculosis diagnostics and is required for the examination of outbreaks.
      Molecular methods for fine typification of isolated bacterial strains and their
      subsequent comparison constitute an important tool in the infection epidemiology
      investigation of incident clustering. OBJECTIVE AND METHOD: The objective of this
      work is the description of a tuberculosis infection chain in Saxony-Anhalt, which
      was discovered by means of a molecular biological method. The conservative method
      represents the environment investigations for the expedient selection of contact
      persons. The investigations always take 2 directions in the process. On the one
      hand, it is searched for the still unknown source of infection. On the other
      hand, persons are to be identified, who have been infected before the diagnosis
      became known. The diagnostics for contact persons includes besides the lung X-ray
      checkup exam, the Mendel Mantoux tuberculin skin test (THT), sputum tests and the
      Interferon Gamma (INF-gamma) tests (IGRA). In described case, the molecular
      biological method of spoliogotyping was employed as additional instrument.
      Therein, fingerprint maps of the patients' tuberculosis strings were created and
      compared. Infection chains resulting from the environment investigations were
      thereby secured. RESULTS: We report on a tuberculosis outbreak in a district of
      the state of Saxony-Anhalt, which occurred in the time from June 2007 to May
      2010. As result of the environment investigations, an infection chain of 13 ill
      patients (77% ?, 23% ?) was identified. In 11 cases the correlation of the
      infection chain was proven by spoligotyping (9 ?, 2 ?). 2 cases (1 ?, 1 ?)
      without verification of the pathogen cannot be attributed on basis of the
      epidemiological correlations.

PMID- 21866496
TI  - [Public reporting in health care: the impact of publicly reported quality data on
      patient steerage].
AB  - BACKGROUND: Public reporting (PR) has been gaining more weight as a mechanism for
      patient steerage. According to the theory of PR, patients use information about
      the quality of health care providers before making decisions and selecting health
      care providers. This paper contributes further knowledge on the effectiveness of
      PR and identifies critical success factors. These should be taken into account
      when implementing PR in the German health care system. METHODOLOGY: The peer
      reviewed English, Spanish, and German language literature was searched in the
      following five databases: The Cochrane Library, Medline (via PubMed), ISI Web of
      Knowledge, EconLit, and PsycINFO (since 2005). In addition, reference lists of
      the included studies and reviews were screened in order to identify previously
      published studies. RESULTS: In total, 21 studies were identified regarding the
      impact of 12 different PR instruments on patient steerage. An impact could be
      demonstrated in 9 studies, 7 studies showed mixed results, while 5 studies could
      not show any effect on patient steerage. 20 studies were carried out in the US
      environment, 1 study in Germany. The most researched instrument is the New York
      State Cardiac Surgery Reporting System (N=8). CONCLUSION: PR can be effective in
      steering patients when seeking a health-care provider, especially for elective
      procedures. To be successful, information provided must be reliable, easily
      understandable, should further represent real news, and be disseminated widely.
      Besides this, it has to be applicable and modifiable according to individual
      preferences.

PMID- 21866497
TI  - HIV/AIDS among American Indians/Alaska Natives living in Montana: a descriptive
      study.
AB  - This study examined the epidemiology of HIV among AI/ANs in Montana. Barriers to
      HIV testing and motivations to test also were explored. Analysis of data revealed
      that there were no significant changes in regard to HIV/AIDS case rates,
      demographic characteristics, or risk behaviors of AI/ANs infected with HIV/AIDS
      since reporting began in 1985. Barriers to testing included low perception of
      risk and fear of people finding out about the test. Despite major barriers to
      testing identified in this study, AI/ANs appeared to be testing at a higher rate
      than Whites.

PMID- 21866498
TI  - Does pedometer goal setting improve physical activity among Native elders?
      Results from a randomized pilot study.
AB  - We examined if step-count goal setting resulted in increases in physical activity
      and walking compared to only monitoring step counts with pedometers among
      American Indian/Alaska Native elders. Outcomes included step counts, self
      reported physical activity and well-being, and performance on the 6-minute walk
      test. Although no significant between-group differences were found, within-group
      analyses indicated that elders significantly improved on the majority of step
      count, physical activity, health-related quality of life, and 6-minute walk
      outcomes.

PMID- 21866499
TI  - Do American Indian mascots = American Indian people? Examining implicit bias
      towards American Indian people and American Indian mascots.
AB  - Empirical examinations of American Indian (AI) mascots have only recently entered
      into the discourse of mainstream psychology. The present studies examined
      implicit attitudes of non-AI people towards AI mascots and the extent to which
      they are related to attitudes towards AI people. Significant concordance was
      observed between negative bias toward AI mascots and AI people. Negative AI
      mascot bias also predicted stereotype-consistent expectations of an AI person.
      The implications of these findings are discussed.

PMID- 21866500
TI  - It's all about healing.

PMID- 21866501
TI  - Research methods for design practitioners to evaluate facilities.

PMID- 21866502
TI  - Rooftop hospital gardens for physical therapy: a post-occupancy evaluation.
AB  - OBJECTIVE: The goal of this study was to understand successes and weaknesses of a
      rooftop hospital garden used primarily for physical therapy. BACKGROUND:
      Literature on the healing benefits of nature and designed outdoor spaces in
      healthcare contexts continues to become more focused on specific patient
      populations. This study contributes to the knowledge of rooftop hospital gardens
      and gardens for physical rehabilitation. METHODS: A post-occupancy evaluation was
      conducted using interviews with a lead therapist and landscape architect,
      behavior mapping, a staff survey, and a patient questionnaire. RESULTS: The
      designer and administrative staff perceived high accessibility while patients and
      staff reported low accessibility. Patients reported high satisfaction with the
      garden while staff reported little time for garden use. Poor maintenance
      decisions resulted in decreased functional and aesthetic value. CONCLUSIONS:
      Garden elements take on added layers of meaning and value to users seeking to
      escape the indoor environment, placing increased importance on evidence-based
      site design. Multiple perspectives must be considered in facility and garden
      master planning. Finally, designers and horticultural therapists must be retained
      in garden management to preserve and enhance garden functionality.

PMID- 21866503
TI  - Peer review and the development of a science.

PMID- 21866504
TI  - A framework for evaluating evidence in evidence-based design.
AB  - A major challenge in the evidence-based design (EBD) practice model has been in
      determining the degree of credibility of specific (or a body of) evidence. This
      challenge has remained one of the key impediments to the broader adoption of EBD.
      Borrowing from evidence-based medicine and evidence-based practice literatures,
      this paper proposes a framework for evaluating evidence in EBD. Key to the
      proposed framework is the separation of the evaluation of strength and quality of
      evidence from the evaluation of appropriateness and feasibility in a specific
      application context.

PMID- 21866506
TI  - Ten suggestions for increasing rigor in architecture and design.

PMID- 21866505
TI  - Arousing curiosity: when hospital art transcends.
AB  - Evolutionary and emotional congruence theoretical perspectives support the use of
      certain types of artwork to reduce stress and promote improved outcomes in
      healthcare settings. This paper explores the artwork of three artists whose work
      falls outside the traditional representational art supported by these theoretical
      perspectives. The concept of curiosity as a common thread is proposed as the
      underlying theory in an effort to explain the success of such work in achieving
      positive outcomes for patients, families, and staff. Other concepts are explored
      as contributing theoretical frameworks. Research is needed to determine the
      impact of this emerging type of artwork and the implications of findings for
      individuals who create--as well as for those who select--art for healthcare
      settings.

PMID- 21866507
TI  - Lactation space design: supporting evidence-based practice and the baby-friendly
      hospital initiative.
AB  - The design of spaces where lactation occurs within a healthcare facility often
      lacks careful attention to the environmental requirements of breastfeeding.
      Although numerous studies evoke overwhelming support for lactation initiation in
      hospitals, few designers may understand the importance of such spaces.
      Furthermore, many designers may be unaware of the contributions they may make to
      this initiative. Countless studies that support the philosophy that breast milk
      is the best nutritional option for babies have been conducted. There are many
      health and economic advantages of breastfeeding for babies, mothers, and
      communities. Research suggests that exclusive breastfeeding for the first 6
      months of life reduces the rate of illness throughout infancy and beyond, saves
      lives, and could save billions of dollars in the United States each year.The Baby
      Friendly Hospital Initiative is a global program established to promote within
      healthcare facilities the facilitation of breastfeeding infants from birth.
      Results of this initiative show a significant increase in breastfeeding rates in
      many countries. The intuitive design response to such favorable research is to
      enhance the lactation environment, assuming that mothers who feel comfortable in
      lactation spaces will use them more frequently, which promotes lactation in
      healthcare facilities. Considering the numerous research-supported advantages of
      breastfeeding, designers would be prudent to seek and apply knowledge of the
      environmental needs to the design of lactation spaces. This may be achieved by
      becoming familiar with lactation procedures to understand the circulation,
      adjacencies, and spatial requirements of lactation programs. Incorporating this
      information into the design may allow the development of ideal spaces that
      facilitate lactation.

PMID- 21866508
TI  - A comparison of parent satisfaction in an open-bay and single-family room
      neonatal intensive care unit.
AB  - OBJECTIVE: The purpose of this research was to test the hypothesis that parental
      satisfaction with neonatal intensive care is greater in a single-family room
      facility as compared with a conventional open-bay neonatal intensive care unit
      (NICU). METHODS: This investigation was a prospective cohort study comparing
      satisfaction survey results for parents who responded to a commercially available
      parent NICU satisfaction survey following the provision of NICU care in open-bay
      and single-family room facilities. A subset of 16 items indicative of family
      centered care was also computed and compared for these two NICU facilities.
      RESULTS: Parents whose babies received care in the single-family room facility
      expressed significantly improved survey responses in regard to the NICU
      environment, overall assessment of care, and total survey score than did parents
      of neonates in the open-bay facility. With the exception of the section on
      nursing in which scores in both facilities were high, nonsignificant improvement
      in median scores for the sections on delivery, physicians, discharge planning,
      and personal issues were noted. The total median item score for family-centered
      care was significantly greater in the single-family room than the open-bay
      facility. CONCLUSIONS: Parental satisfaction with care in the single-family room
      NICU was improved in comparison with the traditional open-bay NICU. The single
      family room environment appears more conducive to the provision of family
      centered care. Improved parental satisfaction with care and the potential for
      enhanced family-centered care need to be considered in decisions made regarding
      the configuration of NICU facilities in the future.

PMID- 21866509
TI  - Influence of positive distractions on children in two clinic waiting areas.
AB  - OBJECTIVE: To examine the influence of positive distraction on the behavior and
      activity of children in two clinic waiting areas. BACKGROUND: People spend a
      considerable proportion of time waiting in hospitals. Studies show that the
      quality of waiting environments influences the perception of quality of care and
      caregivers, that perception of waiting time is a better indicator of patient
      satisfaction than actual waiting time, and that the waiting environment
      contributes to the perception of wait time. In fact, the attractiveness of the
      physical environment in waiting areas has been shown to be significantly
      associated with higher perceived quality of care, less anxiety, and higher
      reported positive interaction with staff. Can positive distractions in waiting
      areas improve the waiting experience, as indicated by the behavior and activities
      of children waiting for treatment? METHOD: Five distraction conditions were
      randomly introduced in the waiting area of the dental and cardiac clinics of a
      major pediatric tertiary care center through a single plasma screen intervention.
      The attention, behavior, and activities of waiting children were recorded. Data
      on 158 pediatric patients were collected over 12 days during December 2008 and
      January 2009. RESULTS: Data analysis shows that the introduction of distraction
      conditions was associated with more calm behavior and less fine and gross
      movement, suggesting significant calming effects associated with the distraction
      conditions. Data also suggest that positive distraction conditions are
      significant attention grabbers and could be an important contributor to improving
      the waiting experience for children in hospitals by improving environmental
      attractiveness.

PMID- 21866510
TI  - Letters to the editors.

PMID- 21866512
TI  - Ultrasonography of the rumen in 30 Saanen goats.
AB  - This study describes the results of ultrasonographic examination of the rumen in
      30 healthy Saanen goats. A linear or convex transducer with a variable frequency
      of 5 to 13 MHz was used to scan standing, non-sedated goats. The location and
      size of the rumen, the distance between the wall of the rumen and abdominal wall
      and the appearance and size of the gas, fibre mat and fluid layers of the ruminal
      contents were assessed. The rumen was seen as a large organ medial to the left
      abdominal wall. The wall of the rumen appeared as a thick echogenic line. The
      longitudinal groove was seen as an echogenic notch, which divided the rumen into
      the dorsal and ventral sacs. The rumen could be visualized from the 9th to 12th
      intercostal space (ICS) and flank on the left side in all the goats. The rumen
      was largest in the 12th ICS at 41.6 +/- 5.13 cm and smallest in the 8th ICS at
      11.3 +/- 4.29 cm. The dorsal sac of the rumen was largest in the left cranial
      flank (17.4 +/- 4.43 cm) and the ventral sac was largest in the 12th ICS on the
      left (29.1 +/- 6.03 cm). In the cranial left flank, the rumen was situated
      immediately adjacent to the abdominal wall in all the goats. The spleen was
      located between the rumen and abdominal wall in the 8th to 12 th ICS in many of
      the goats. The gas, fibre mat and fluid layers of the ruminal contents could be
      visualized in all the goats. The gas layer was 9.9 +/- 3.05 cm, the fibre mat
      layer 16.0 +/- 4.55 cm and the fluid layer 12.2 +/- 5.57 cm.

PMID- 21866513
TI  - Pulmonary edema at recovery after colic operation with in-situ nasogastric tube
      in a horse.
AB  - After an uneventful general anesthesia, in a horse negative pressure pulmonary
      edema developed due to acute upper airway obstruction during the anesthetic
      recovery phase after colic surgery. No pathologic alteration of respiration was
      observed until the horse stood up and began suffocating. The horse had recovered
      with the nasogastric tube in situ. This, together with the postmortem diagnosis
      of laryngeal hemiplegia resulted in impairment of airflow through the larynx and
      development of pulmonary edema. Our objective is to alert clinicians about the
      possible hazard of recovery with an in-situ nasogastric tube.

PMID- 21866515
TI  - [Chemical risk after flooding].

PMID- 21866514
TI  - Antibiotic treatments of a methicillin-resistant Staphylococcus pseudintermedius
      infection in a dog: a case presentation.
AB  - We report the antibiotic treatments administered to a female dog with mastitis
      and successive pyoderma. Microbiological investigations allowed the
      identification of Staphylococcus pseudintermedius after 54 days of various
      antibiotic treatments. The isolate carried the mecA gene and was resistant to 9
      of 15 tested antibiotics. Consistent antibiotic treatment of the infection was
      possible only after accurate microbiological diagnosis.

PMID- 21866516
TI  - Effects of deslorelin implants on ovarian cysts in guinea pigs.

PMID- 21866517
TI  - [Frequency of gene defects in selected European retriever populations].

PMID- 21866523
TI  - Cytoarchitectural and surface ultrastructural analysis of the olfactory
      epithelium of Oreochromis nilotica (Linnaeus).
AB  - The olfactory organ of Oreochromis nilotica was studied by means of light and
      scanning electron microscopes. The oval shaped olfactory apparatus consists of 19
      20 lamellae radiating from a central raphe. The receptor epithelium occupies the
      restricted area of the middle swollen region of the lamellae and is framed with
      receptor cells (both ciliated and microvillous) and rod cells. The larger part of
      the lateral surface of the olfactory lamella is covered with non-receptor
      epithelium, which is made up of stratified epithelial cells and mucous cells. The
      functional significance of various cells lining the olfactory epithelium of this
      fish are discussed.

PMID- 21866524
TI  - Analysis of foramen ovale with special emphasis on pterygoalar bar and
      pterygoalar foramen.
AB  - The foramen ovale is of great surgical and diagnostic importance in procedures
      like percutaneous trigeminal rhizotomy for trigeminal neuralgia, transfacial fine
      needle aspiration technique in perineural spread of tumour, and
      electroencephalographic analysis. This study presents the anatomic variations in
      dimensions, appearance, number of foramen ovale (FO), and presence of pterygoalar
      bar and pterygoalar foramen. For the present study ninety dry adult human skulls
      were utilised. Anterioposterior (length) and transverse (width) diameters of FO
      were measured, and the presence of pterygoalar bar and foramen were observed. The
      most common shape of FO observed was like a figure 'D'. The ranges of
      anteroposterior diameter of the right and left FO were 8.5-4.5 mm and 10-3 mm,
      respectively. The mean length of the right FO was 6.60 mm while that of the left
      FO was 6.26 mm. The ranges of transverse diameter (width) of both right and left
      foramen were 2.5-6 mm and 2-5 mm, respectively. The mean transverse diameter of
      the right FO was 3.70 mm and that of left was 3.34 mm. Bony spur in FO was seen
      in 6.66% of cases. A complete pterygoalar bar and foramen were observed in seven
      cases unilaterally, and in one case it was bilateral. Anteroposterior and
      transverse diameters of right FO were greater than left. Anatomical
      understanding, including the size, shape of FO, and presence of pterygoalar bar,
      has immense surgical and diagnostic importance.

PMID- 21866525
TI  - Biocompatibility of bone graft substitutes: effects on survival and proliferation
      of porcine multilineage stem cells in vitro.
AB  - Bone graft substitutes (BGS) are widely used in clinical practice. For stem
      cellbased approaches to bone tissue engineering BGS need to show sufficient
      biocompatibility in the in vitro setting. This study was designed to demonstrate
      the influence of six different BGS on the proliferation and metabolic activity of
      porcine mesenchymal multilineage stem cells (pMSC) in vitro. Bone-marrow derived
      pMSC were cultivated for 24 hours with the eluates of six different BGS. The
      eluates were generated by incubating the BGS three times in succession for 24
      hours with a culture medium and collecting the supernatants. pMSC vitality and
      proliferation in the presence of eluates from the first, second, and third
      incubation were assessed by WST-test quantification of metabolically active
      cells. Culture of pMSC with eluates in all cases resulted in decreased cell
      numbers in an eluate concentration-dependent manner. At least a 65% loss of cells
      compared to controls (culture medium without eluates) could be observed in the
      presence of undiluted eluates. The negative influence of eluates varied
      significantly among BGS. In all cases, second and third eluates were less potent
      in their negative effects on cellular vitality/proliferation. In conclusion, the
      BGS examined here should be submitted to thorough preincubation before in vitro
      use for cell-based constructs to maximize cell viability for the tissue
      engineering of bone.

PMID- 21866526
TI  - Histomorphometric and sympathetic innervation of the human posterior intercostal
      artery and its clinical importance.
AB  - The purpose of this investigation was to study the characteristics of arterial
      wall and sympathetic innervation of the human posterior intercostal artery (PIA)
      in order to assess its suitability as an arterial graft for vascular surgeries.
      Fifty PIA samples were obtained from 25 cadavers (18 males and 7 females).
      Samples were divided into three age groups: group 1: 19-40 years; group 2: 41-60
      years; and group 3 over 61 years. Sections (5 MUm-thickness) of each sample were
      taken and stained with haematoxylin-eosin, Verhoeff's-Van Gieson. Five samples
      were processed for tyrosine hydroxylase immunostaining. The differences in the
      thickness of tunica intima were not statistically significant when group 1 was
      compared with group 2 (p = 0.798), but significant differences were observed in
      the thickness of the tunica intima when comparing group 2 with group 3 (p =
      0.012) and group 3 with group 1 (p = 0.002). The tunica media was not
      statistically significant when group 1 was compared with group 2 (p = 0.479).
      However, significant differences were observed in the thickness of the tunica
      media when comparing group 2 with group 3 (p = 0.001) and group 3 with group 1 (p
      = 0.011). The mean (SD) number of elastic laminae in group 1, group 2, and group
      3 were 7.88 +/- 0.69, 6.62 +/- 0.51, and 4.56 +/- 0.82, respectively. Tunica
      intima/media ratios in groups 1, 2, and 3 were found to be 0.09 +/- 0.01, 0.11 +/
      0.02, and 0.27 +/- 0.16, respectively. Tyrosine hydroxylase immunostaining
      revealed that sympathetic fibres are found mainly in the tunica adventitia and at
      the adventitia-medial border. The sympathetic nerve fibre area and sympathetic
      index were found to be 0.004 mm2, and 0.151 mm(2), respectively. PIA has
      relatively thin intima and media, which are favourable features regarding its
      potential suitability as an alternate coronary bypass conduit.

PMID- 21866527
TI  - Panoramic radiomorphometric parameters in Polish patients.
AB  - Panoramic radiographs are frequently applied in dental radiodiagnostics and might
      serve as a tool for identification of a subject's bone mass. Only in a few
      publications can data on men, younger subjects and larger groups of patients be
      found. No such data are available for the Polish population; therefore, the aim
      of the study was to determine normal ranges of panoramic radiomorphometric
      parameters and examine the influence of gender and age on them. The material
      consisted of 877 digital panoramic radiographs taken in patients aged 20 to 95
      years (mean 48.69 years), including 467 females and 410 males. Panoramic
      parameters such as mandibular height (H) and distance between inferior margin of
      mental foramen and inferior mandibular cortex (h), which are used for calculation
      of panoramic radiomorphometric indices, were estimated and the obtained results
      were subjected to statistical analysis. Gender influenced H and h, while it was
      found that H was age-dependent and h values were similar in all age groups. When
      age and gender were discussed simultaneously, the highest values of H were
      observed in the age group 30-39 years in both genders, followed by a gradual
      decrease with age. However, in females this decrease was more intense than in
      males. The elaborated norms of panoramic radiomorphometric parameters and indices
      in the Polish patients may serve as a source of comparison for radiological and
      clinical applications.

PMID- 21866528
TI  - Variant anatomy of sciatic nerve in a black Kenyan population.
AB  - Knowledge of variant anatomy of the sciatic nerve is important in avoiding
      inadvertent injury during operations in the gluteal region and interpreting
      nondiscogenic sciatica. This variant anatomy may cause piriformis syndrome and
      failure of sciatic nerve block. The variations differ between populations but
      data from Africans is scarce. This study, therefore, investigated variations of
      sciatic nerve in a black Kenyan population. One hundred and sixty-four sciatic
      nerves from 82 cadavers of black Kenyans were exposed by dissection at the
      Department of Human Anatomy, University of Nairobi, Kenya. The level of
      bifurcation, relationship to piriformis, and topographic relations between the
      branches were studied. The results were analysed by SPSS version 16.0 and are
      presented by macrographs. In 33 (20.1%) cases division occurred in the pelvis,
      while in 131 (79.9%) it occurred outside the pelvis. A single trunk sciatic nerve
      exited below the piriformis muscle in 131 (79.9%) cases. In cases of pelvic
      division, the tibial nerve was always infrapiriformic, while the common peroneal
      nerve passed below piriformis in 16 (9.8%) cases, pierced the piriformis in 13
      (7.9%), and passed above it in 4 (2.4%). For those in which division was
      extrapelvic, 110 (67.1%) were in the popliteal fossa, 17 (10.4%) in the middle
      third of the thigh, and 4 (2.4%) in the gluteal region. Where the division was
      pelvic, in 19 (11.6%) cases they continued separately, in 8 (4.9%) the two nerves
      reunited, and in 6 (3.7%) they were connected by a communicating nerve. The
      sciatic nerve in the Kenyan population varies from the classical description in
      over 30% of cases, with many high divisions, low incidence of piriformic course
      of common peroneal nerve, reunion, and unusual connection between common peroneal
      and tibial nerves. These variations may complicate surgery and interpretation of
      sciatic neuropathy. Preoperative nerve imaging and extra operative diligence in
      the gluteal region and the back of the thigh are recommended.

PMID- 21866529
TI  - Morphological study of the calcaneofibular ligament in cadavers.
AB  - The aim of the present study was to investigate the anatomical and morphological
      characteristics and the maximum elongation of the calcaneofibular ligament (CFL)
      in cadavers. In a sample of 72 cadaveric lower limbs the mean values of length,
      width, thickness, and angle with the sagittal plane were recorded for the CFL.
      The mean ligament's length was 31.8 mm, and the mean width and thickness were 4.4
      mm and 1.5 mm respectively. The mean angle with the sagittal plane was 51.11
      degrees . In 72.2% of the lower limbs studied, the ligament presented one band,
      while 22.2% and 5.6% of them were two-banded and three-banded respectively. A
      common origin with the anterior talofibular ligament (TFL) was found in 24 of the
      feet (33%). There were also 4 cases in which the anterior TFL was absent.
      Finally, we measured the maximal elongation of the ligament during extreme
      inversion and simultaneous dorsal flexion and found it to be 2.88 mm on average.
      We noticed and statistically verified that women presented a greater elongation
      compared to men. A precise knowledge of the origin, insertion, direction, and
      morphology of CFL is critical for ligament injuries in ankle sprains and during
      ankle reconstruction. Ligament elasticity plays an important role in the range of
      ankle motion and ligament shearing. Male and female ankle joints differ in
      several anthropometric characteristics and thus the genre differences in ligament
      elongation are of great interest.

PMID- 21866530
TI  - Interparietal and pre-interparietal bones in the population of south coastal
      Andhra Pradesh, India.
AB  - The squamous occipital bone consists of two parts: a cartilaginous supraoccipital
      part below and a membranous interparietal (IP) part above the highest nuchal
      line. The IP part develops from two pairs of ossification centres which form the
      two lateral plates and a median central piece. Any anomalous ossification of
      these centres gives rise to IP bones. Occasional separate ossified part of the IP
      region give rise pre-interparietal (PIP) bones which, when present, should be
      within the territory of the lambdoid suture. The present study was undertaken to
      observe the incidence of IP and PIP bones in skulls belonging to the south
      coastal population of Andhra Pradesh, India, hitherto unreported. In a total of
      84 skulls, IP bones were found in 8 (9.5%) skulls and PIP bones in 6 (7.1%)
      skulls. The occurrence of IP and PIP bones can be correlated with the development
      of the squamous part of the occipital bones, and any alterations in the fusion of
      its ossification centres and its nuclei result in these anomalous bones.
      Knowledge of these bones may be important in dealing with situations resulting
      from fractures of occipital bones, and to rule out their incidence between races
      or populations in different parts of the world.

PMID- 21866531
TI  - Computerised 3-D anatomical modelling using plastinates: an example utilising the
      human heart.
AB  - Computerised modelling methods have become highly useful for generating
      electronic representations of anatomical structures. These methods rely on
      crosssectional tissue slices in databases such as the Visible Human Male and
      Female, the Visible Korean Human, and the Visible Chinese Human. However, these
      databases are time consuming to generate and require labour-intensive manual
      digitisation while the number of specimens is very limited. Plastinated
      anatomical material could provide a possible alternative to data collection,
      requiring less time to prepare and enabling the use of virtually any anatomical
      or pathological structure routinely obtained in a gross anatomy laboratory. The
      purpose of this study was to establish an approach utilising plastinated
      anatomical material, specifically human hearts, for the purpose computerised 3-D
      modelling. Human hearts were collected following gross anatomical dissection and
      subjected to routine plastination procedures including dehydration (-25(o)C),
      defatting, forced impregnation, and curing at room temperature. A graphics
      pipeline was established comprising data collection with a hand-held scanner, 3-D
      modelling, model polishing, file conversion, and final rendering. Representative
      models were viewed and qualitatively assessed for accuracy and detail. The
      results showed that the heart model provided detailed surface information
      necessary for gross anatomical instructional purposes. Rendering tools
      facilitated optional model manipulation for further structural clarification if
      selected by the user. The use of plastinated material for generating 3-D
      computerised models has distinct advantages compared to cross-sectional tissue
      images.

PMID- 21866532
TI  - The structure of the penis with the associated baculum in the male greater cane
      rat (Thryonomys swinderianus).
AB  - In this study, the structures of penises of eight sexually mature male greater
      cane rats were examined at both macroscopic and histological levels. Each animal
      was sacrificed after anaesthesia with ether and then dissected open with the
      penis exposed from its root. The penises were first grossly examined, measured,
      and then prepared for histological examination. From this study it was observed
      that the body size has no allometry with penile size, but the testicular weight
      correlated with Os penis length in the greater cane rat. Grossly, the penis which
      was whitish in colour, with a mean length of 5.46 +/- 0.36 cm, has no obvious
      collum penis but a flexura that turns it caudo-ventral and separates the corpus
      and glans penis. There was the presence of cornified papillae covering parts of
      the corpus and glans penis as well as a blind sac sacculus urethralis under the
      urethra on the glans penis. Histologically, the corpora cavernosa penis were
      completely separated by a connective tissue septum which sent the trabeculae
      network into the cavernous tissues and replaced the caverns as it moves from
      corpus to glans penis. The Os penis formed through endochondral ossification
      after 42 months of age in this animal. Therefore, from a histological standpoint,
      the cane rat penis belongs to the intermediate type. In conclusion, these
      findings provide vital information on the penile anatomy of the greater cane rat,
      which will serve as a basis for comparing penile morphology among the suborder
      hystricomorpha and expand knowledge of the reproductive biology in this animal.

PMID- 21866533
TI  - Antero-medial approach to the wrist: anatomic basis and new application in cases
      of fracture of the lunate facet.
AB  - The Henry approach is the classical anterolateral surgical exposure of the volar
      aspect of the distal radius. This approach does not allow good access to the
      medial side of the volar distal radius (lunate facet) and the distal radio-ulnar
      joint, unless it is extended proximally, retracting the tendons and the median
      nerve medially, which can cause some trauma. The purpose of our study was to
      investigate the anatomic basis and to outline the advantages of the unusual
      anteromedial approach, reporting our experience in the treatment of 4 distal
      radius fractures, with a 90 degrees  or 180 degrees  twist of the lunate facet,
      and 10 wrist dissections on cadavers. The average follow-up was 68.8 months
      (range 18 to 115 months). In our series, this approach did not cause any nerve
      injuries or any sensory loss of the distal forearm and the palm. All the
      fractures of the lunate facet and of the radial styloid process healed. One
      patient with an ulnar styloid process fracture associated showed pseudarthrosis,
      but with no instability of the distal radio-ulnar joint or pain on the ulnar
      side. Using the criteria of Green and O'Brien, modified by Cooney, the results
      were: excellent in two cases, good in one case, and average in another. The
      evaluation of arthritis according to Knirk and Jupiter's classification showed
      grade 0 in three cases and grade 3 in one case with osteochondral sclerosis. We
      showed that the anteromedial approach is reliable and convenient in the case of
      fractures situated in the antero-medial portion of the radius, for the double
      objective of reducing the fracture under direct control and checking the
      congruence of the distal radio-ulnar joint.

PMID- 21866534
TI  - The suprascapular notch: its morphology and distance from the glenoid cavity in a
      Kenyan population.

PMID- 21866535
TI  - Professor Wieslaw Lasinski (1915-2010).

PMID- 21866536
TI  - Professor Zygmunt Urbanowicz (1931-2011) - biography.

PMID- 21866537
TI  - The emergence of personality in animals: the need for a developmental approach.
AB  - Interest has been growing among behavioral biologists in individual differences
      in animal behavior of the kind that can be considered to reflect differences in
      personality. Once considered the exclusive domain of human psychology, biologists
      have found evidence for personality across a wide range of species, while
      behavioral ecologist and theoretical biologists recognize the likely evolutionary
      origins and contribution to fitness of such. However, until recently most work
      has concentrated on ultimate questions of fitness and thus on adult animals, with
      little attention given to proximate, developmental origins. This is now changing,
      as approaches to studying animal personality broaden and methodologies are
      developed enabling this to be studied across periods of near continuous and often
      rapid ontogenetic change. Debate continues, however, about the right
      methodologies to characterize the phenomenon and attempt to do so in a comparable
      manner across taxa that differ as widely in the expression of "personality" as
      insects and mammals. This makes it necessary to discuss this field in an
      interdisciplinary context among psychologists and biologists, and was the
      rational for a meeting on "The Emergence of Personality in Animals" held in May
      2010 at the Center for Interdisciplinary Research (Zentrum fur Interdisziplinare
      Forschung; ZiF), Bielefeld, Germany. The diversity of topics, viewpoints and
      organisms covered and the excitement created by the ensuing discussions is
      reflected in the resulting collection of papers forming this special issue.

PMID- 21866538
TI  - Stability and instability of childhood traits: implications for personality
      development of animals.
AB  - Concepts of animal personality and human temperament are nearly identical, both
      emphasizing overt behaviors rather than conscious processes, and assuming a
      primary role of biology in shaping individual differences. A point of divergence
      is emphasis on development among temperament scholars. Whereas most definitions
      of personality and temperament emphasize differential continuity-the maintenance
      of individual differences in behavioral tendencies over time-several behaviors
      demonstrate absolute discontinuity-age-related changes in mean levels. Attention
      to species-wide changes in behaviors may generate insight regarding the forces
      that govern individual differences. Differential continuity may also be
      heterotypic, with an inferred genotypic attribute being manifest in different
      behaviors at different ages. Structural continuity-persistence of correlational
      patterns among variables at different ages-represents a tool for identifying
      coherence in the common underpinnings of these diverse behaviors. This article
      describes research exemplifying these forms of continuity in humans, and suggests
      potential implications for animal personality investigations.

PMID- 21866540
TI  - The effect of siblings on early development: a potential contributor to
      personality differences in mammals.
AB  - Although most mammals grow up in the company of same or different age sibs (or
      half sibs), surprisingly little attention has been given to how relations among
      them might influence the development of individual differences in morphology,
      physiology, and behavior. Here we review evidence from our work on domestic and
      wild European rabbits, and more recently on laboratory rats, mice, and domestic
      cats, supporting the proposition that in mammals early sibling relations
      contribute to the development of individual differences in these three domains
      and thereby to long-term behavioral differences of the kind we might consider
      part of an animal's behavioral style or personality. First we report a consistent
      and marked negative relation between litter size and individuals' body mass at
      birth and weaning, as well as marked within-litter differences in prenatal body
      mass and placental efficiency. We then report individual differences in
      preweaning behaviors associated with these morphological variables such as
      position occupied in the litter huddle and development of motor ability, as well
      as physiological differences in thermoregulation, immune parameters, and
      endocrine indicators of stress. Finally, we report first evidence from wild
      rabbits that early relations among littermates may have long-term consequences
      for individual differences in behavioral style. We conclude that in mammals,
      individual differences in early growth, physiology and behavior potentially
      important for the development of animal personality, are shaped to an appreciable
      extent by early sibling relations and that this little-researched field deserves
      closer attention.

PMID- 21866539
TI  - Similarity in temperament between mother and offspring rhesus monkeys: sex
      differences and the role of monoamine oxidase-a and serotonin transporter
      promoter polymorphism genotypes.
AB  - Temperament is usually considered biologically based and largely inherited,
      however, the environment can shape the development of temperament. Allelic
      variation may confer differential sensitivity to early environment resulting in
      variations in temperament. Here we explore the relationship between measures of
      temperament in mothers and their first-born offspring and the role of genetic
      sensitivity in establishing the strength of these associations. Temperament
      ratings were conducted on 3- to 4-month-old rhesus monkeys after a 25-hr
      biobehavioral assessment. Factor analysis revealed a four-factor structure of
      temperament. Females assessed as infants have reproduced and their offspring have
      also been evaluated through the standardized testing paradigm. Canonical
      correlation analysis revealed statistically significant associations between
      factor scores of mothers and sons, but not mothers and daughters. Further,
      offspring possessing the high activity, "low risk," alleles of the rhMAOA-LPR or
      rh5-HTTLPR showed statistically significant canonical correlations, whereas those
      possessing other alleles did not, suggesting differential genetic sensitivity to
      the normative early experience of maternal temperament.

PMID- 21866541
TI  - Optimizing temperament through litter size in short-lived, iteroparous mammals in
      seasonal environments.
AB  - A number of short-lived, iteroparous animal species have small broods in the
      early breeding season and larger broods in later breeding season. Brood size
      affects not only offspring size, but as recent results suggest, may also affect
      offspring's temperament, hormonal status, and aggression as adults. Most
      populations of short-lived, iteroparous mammals fluctuate predictably over the
      season, with low densities in winter, increasing densities in summer and a
      population peak in late summer followed by a population breakdown. If animals
      live only through parts of the season, possibly such differences in density and
      hence also in social environments among seasons require different personality
      types to increase individual fitness. We present data on behavior of European
      rabbits from a field enclosure study. These data clearly show that aggressiveness
      is higher in young from smaller litters than in young from larger litters, and
      smaller litters are usually born during the early breeding season. Moreover, our
      data suggest that behavioral types of the young rabbits are stable over time, at
      least during their subadult life. We suggest, that changes in mean litter size
      over the course of the breeding season may not only be a product of mothers' age
      or food availability, but may also have an adaptive function by preparing
      offspring characteristics for adulthood in a social environment undergoing
      predictable density changes within the season.

PMID- 21866542
TI  - Early development influences ontogeny of personality types in young laboratory
      rats.
AB  - Features of an individual's early development are frequently reported to alter
      the postnatal ontogeny in litter-bearing mammals with respect to various
      physiological parameters. We hypothesized that such effects might also apply to
      the ontogeny of personality types. On the one hand, litter size effects by means
      of more contacts with littermates, might lead to the development of more
      offensive types. On the other hand, smaller and less developed young from larger
      litters might be less offensive due to their lower physical capabilities to deal
      with challenging situations. We studied these contrasting hypotheses in young
      rats, which we tested in a battery of emotionality tests. There were clear
      indications for the existence of distinct behavioral types by means of
      consistencies in behavioral responses within and across contexts. Based on these
      responses, we calculated three new variables by PCA, which we interpreted to
      mainly reflect boldness, exploration, and anxiety. Overall, our results strongly
      suggest that the early development alters the ontogeny of personality types, with
      heavier individuals being bolder and more explorative. Furthermore, body mass and
      litter size influenced the changes in the behavioral responses in successive
      tests, further supporting the importance of the litter size-dependent body mass
      for the ontogeny of personalities. Anxiety also depended on litter size, however,
      in a nonlinear way. Animals born to litters of small or large sizes had higher
      scores, whereas individuals from medium-sized litters were less anxious. This
      optimum curve indicates that opposing effects of litter size are involved in
      shaping personalities in young rats.

PMID- 21866543
TI  - "Personality" in laboratory mice used for biomedical research: a way of
      understanding variability?
AB  - The mouse, including countless lines of transgenic and knockout mice, has become
      the most prominent model organism in biomedical research. Behavioral
      characterization is often conducted in batteries of short tests on locomotion,
      anxiety, learning and memory, etc. In such tests, any individual differences
      within groups are usually considered to be disturbing variance. In order to
      reduce variance in experimental animal research enormous efforts of
      standardization have been made. While a substantial reduction of variability has
      been reached compared to the earlier years of experimental animal studies a
      considerable amount of inter-individual differences still seems to escape
      standardization. This effect is demonstrated and evaluated by re-analyzing data
      from two experiments conducted in our laboratory with inbred mice. Interestingly,
      behavioral patterns of individual animals seem to be correlated across context
      and time. In evolutionary biology, "animal personalities" have been discussed
      recently to comprise such stable patterns. We argue here, that nonrandom
      behavioral correlations across contexts and time might underlie the variability
      commonly found in biomedical mouse studies.

PMID- 21866544
TI  - Unfolding personalities: the importance of studying ontogeny.
AB  - We aim to stimulate an ontogenetic approach to personalities. We explain the
      importance of studying development for understanding proximate and ultimate
      aspects of personality and critically discuss, partly by perhaps provocative
      statements, our current lack of knowledge and potential approaches to the study
      of personality development. We first clarify some terminology and argue for a
      difference between behavioral profiles (BP; at the descriptive level) and
      personality (at the explanatory level). We then focus on the issue of temporal
      stability of personality, arguing that based on evolutionary theory,
      neurophysiological knowledge, and recent findings, personality is probably less
      stable than often thought. Next we consider the potential influence of genes,
      discussing gene by environment correlations and interactions and argue that
      developmental changes in the regulation of DNA expression are probably more
      relevant than individual differences in DNA sequence. We end by suggesting
      perspectives for future research.

PMID- 21866545
TI  - Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked
      immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a
      two-stage design with a preliminary performance study and a mass screening in
      southern China.
AB  - A two-stage study was conducted in southern China to determine and validate an
      optimal combination of Epstein-Barr virus (EBV)-related seromarkers for
      nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers
      [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG,
      Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA)
      and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected
      by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337
      controls. An optimal combination of seromarkers for NPC diagnosis was selected
      using logistic regression models. Results showed that the diagnostic performances
      of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the
      same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified
      as the optimal combination, with an area under the receiver operating
      characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a
      specificity of 94.1% for classification of NPCs vs. controls. In the second
      stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC
      were recruited into a population-based NPC screening program from May 2008 to
      February 2009 in Sihui City, China. Their sera were tested simultaneously by both
      the new and the traditional screening schemes and eight early stage NPC patients
      were subsequently histopathologically confirmed. The traditional and the new
      screening schemes had comparable specificity (estimated as 98.5%), but the
      sensitivity of the new scheme (75.0%) was significantly higher than that of the
      traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA
      outperforms the traditional NPC screening scheme and could become the preferred
      serodiagnostic strategy for NPC screening in high-incidence areas.

PMID- 21866546
TI  - Induction of proinflammatory mediators by CHI3L1 is reduced by chitin treatment:
      decreased tumor metastasis in a breast cancer model.
AB  - Disseminated metastasis accounts for over 90% of breast cancer deaths. Recently,
      elevated serum levels of a glycoprotein known as chitinase-3 like-protein-1
      (CHI3L1) has been correlated with poor prognosis and shorter survival of patients
      with metastatic breast cancer. In this study, we show that there are increased
      levels of CHI3L1 in plasma of tumor-bearing mice and that both tumor cells and
      immune cells express and secrete CHI3L1. However, the biological and
      physiological functions of CHI3L1 are still unclear. We demonstrate that while
      CHI3L1 has an inhibitory role in the expression of interferon-gamma (IFN-gamma),
      CHI3L1 up-regulates pro-inflammatory mediators, C-chemokine ligand 2 (CCL2),
      chemokine CX motif ligand 2 (CXCL2) and matrix metalloproteinase-9 (MMP-9) all of
      which contribute to tumor growth and metastasis. We found that in vitro
      inhibition of CHI3L1 by siRNA suppressed the production of CCL2, CXCL2 and MMP-9
      by macrophages. In vivo treatment of mammary tumor-bearing mice with chitin (beta
      (1-4)-poly-N-acetyl D-glucosamine), a TH(1)  adjuvant and a ligand for CHI3L1,
      promoted immune effector functions with increased production of IFN-gamma and
      decreased CCL2, CXCL2 and MMP-9 expression. In vivo administration of chitin to
      mammary tumor-bearing mice significantly decreased lung metastasis. These studies
      show that CHI3L1 plays a role in tumor progression and that chitin can inhibit
      the pleiotropic effects of CHI3L1 giving support to the idea that CHI3L1 is a
      useful therapeutic target for treatment of breast cancer.

PMID- 21866547
TI  - Intake of dietary fiber, especially from cereal foods, is associated with lower
      incidence of colon cancer in the HELGA cohort.
AB  - The role of dietary fiber on the risk of colon and rectal cancer has been
      investigated in numerous studies, but findings have been inconsistent. The
      purpose of this study was to examine associations between intake of dietary fiber
      and risk of incident colon (including distal and proximal colon) and rectal
      cancer in the prospective Scandinavian HELGA cohort and to determine if fiber
      source (vegetables, fruits, potatoes, cereals) impacted the association. We
      included 1,168 incident cases (691 colon, 477 rectal cancer), diagnosed during a
      median of 11.3 years, among 108,081 cohort members. Sex-specific incidence rate
      ratios (IRRs) of colon and rectal cancer were related to intake of total or
      specific fiber source using Cox proportional hazards models. For men, an inverse
      association was observed between intake of total fiber and the risk of colon
      cancer per an incremental increase of 10 g day(-1) , IRR (95% CI): 0.74 (0.64
      0.86). Intake of cereal fiber per 2 g day(-1) was associated with an IRR of 0.94
      (0.91-0.98), which was also seen for intake of cereal fiber from foods with high
      fiber content (>= 5 g per 100 g product), where the IRR per 2 g day(-1) was 0.94
      (0.90-0.98). In women, intake of cereal fiber per 2 g day(-1) was also associated
      with lower risk of colon cancer, 0.97 (0.93-1.00). No clear associations were
      seen for rectal cancer. Our data indicate a protective role of total and cereal
      fiber intake, particularly from cereal foods with high fiber content, in the
      prevention of colon cancer.

PMID- 21866548
TI  - Prognosis in adenocarcinomas of lower oesophagus, gastro-oesophageal junction and
      cardia evaluated by uPAR-immunohistochemistry.
AB  - Adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia in
      humans are highly invasive tumours with poor prognosis. The localisation of
      urokinase-type plasminogen activator receptor (uPAR) was determined in 66
      patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR
      was expressed in nearly all cases of invasive adenocarcinomas by populations of
      cancer cells, macrophages and myofibroblasts at both the invasion front and the
      tumour core. In areas with high-grade dysplasia or with Barrett's metaplasia
      adjacent to the tumour tissue, no uPAR-immunoreactivity was found. High local
      expression of uPAR, therefore, appears to be a characteristic marker for invasive
      behaviour in this tumour, suggesting that uPAR's contribution to matrix
      degradation during invasive growth is a late event in carcinogenesis. Using a
      scoring system for semiquantitative estimation of uPAR-positivity on
      immmunohistochemically stained specimens, a significant association was found
      between poor overall survival and high uPAR-score for cancer cells in the tumour
      core and for macrophages peripherally at the tumour invasion zone. In
      multivariate analysis, these two uPAR-scores were confirmed as highly significant
      prognostic parameters independent of Tumour, Node, Metastasis (TNM)-stage and
      World Health Organization (WHO) classification. The proteolytic action of these
      malignant and nonmalignant accessory cells thus seemed to follow two main
      patterns: one dominated by uPAR positive cancer cells and one by uPAR-positive
      macrophages. Scoring of uPAR-positivity might be a useful parameter for onset of
      invasion and prognosis in these adenocarcinomas.

PMID- 21866549
TI  - Dietary acrylamide and risk of prostate cancer.
AB  - Acrylamide has been designated by IARC as a "probable human carcinogen." High
      levels are formed during cooking of many commonly consumed foods including French
      fries, potato chips, breakfast cereal and coffee. Two prospective cohort studies
      and two case-control studies in Europe found no association between acrylamide
      intake and prostate cancer. We examined this association in a large prospective
      cohort of 47,896 US men in the Health Professionals' Follow-up Study, using
      updated dietary acrylamide intake from food frequency questionnaires in 1986,
      1990, 1994, 1998 and 2002. From 1986 through 2006, we documented 5025 cases of
      prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models
      to assess the association between acrylamide intake from diet and prostate cancer
      risk overall as well as risk of advanced or lethal cancer. Acrylamide intake
      ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the
      highest quintile; coffee and potato products were largest contributors to intake.
      The multivariate-adjusted relative risk of prostate cancer was 1.02 (95%
      confidence interval: 0.92-1.13) for the highest versus lowest quintile of
      acrylamide intake (p-value for trend = 0.90). Results were similar when
      restricted to never smokers and to men who had prostate-specific antigen (PSA)
      tests. There was no significant association for dietary acrylamide and risk of
      lethal, advanced or high-grade disease, or for different latency periods ranging
      from 0-4 years to 12-16 years. We found no evidence that acrylamide intake,
      within the range of US diets, is associated with increased risk of prostate
      cancer.

PMID- 21866550
TI  - Genetic variation of XPA gene and risk of cancer: a systematic review and pooled
      analysis.
AB  - XPA, a zinc-finger DNA-binding protein, play an important role in both global
      genome and transcription-coupled repair pathways. XPA -4G>A polymorphism was
      identified in the 5' noncoding region, located four nucleotides upstream of the
      ATG start codon. Previous studies have shown that this polymorphism may affect
      mRNA tertiary structure and stability and play a role in susceptibility to
      cancer. However, the results remained controversial. To derive a more precise
      estimation of association between this polymorphism and risk of different types
      of cancer, we performed a meta-analysis based on 36 case-control or case-cohort
      studies, including a total of 11,700 cases and 15,033 controls. We used odds
      ratios with 95% confidence intervals to assess the strength of the association.
      Overall, no significantly elevated cancer risk was found in all genetic models
      when eligible studies were pooled into the meta-analysis. In the stratified
      analyses, we found that individuals with A-allele had a higher risk of lung
      cancer (AA versus GG: OR = 1.25, 95% CI = 1.09-1.43; recessive model: OR = 1.31,
      95% CI = 1.16-1.48). When stratified by ethnicity, significantly elevated risks
      were observed among Asian populations (AA versus GG: OR = 1.31, 95% CI = 1.01
      1.70; dominant model: OR = 1.14, 95% CI = 1.00-1.30). This meta-analysis suggests
      that XPA -4G>A polymorphism is associated with increased lung cancer risk and may
      be a low-penetrant risk factor in Asian ethnicity for cancer development.

PMID- 21866551
TI  - Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease
      outcome.
AB  - This article is the first to show that loss of connexin43 (Cx43) expression in
      colorectal tumors is correlated with significantly shorter relapse-free and
      overall survival. Cx43 was further found to negatively regulate growth of colon
      cancer cells, in part by enhancing apoptosis. In addition, Cx43 was found to
      colocalize with beta-catenin and reduce Wnt signaling. The study represents the
      first evidence that Cx43 acts as a colorectal cancer tumor suppressor and that
      loss of Cx43 expression during colorectal cancer development is associated with
      reduced patient survival. The study has important implications for the assessment
      of Cx43 as a prognostic marker and target in colorectal cancer prevention and
      therapy. Gap junctions consist of intercellular channels that permit direct
      transfer of ions and small molecules between adjacent cells. The gap junction
      channel protein Cx43 plays important roles in cell growth control and
      differentiation and is frequently dysregulated in human cancers. However, the
      functional importance and clinical relevance of Cx43 in cancer development has
      remained elusive. Here, we show that Cx43 is downregulated or aberrantly
      localized in colon cancer cell lines and colorectal carcinomas, which is
      associated with loss of gap junction intercellular communication. The in situ
      protein expression of Cx43 was analyzed in colorectal tumors in a cohort of 674
      patients and related to established clinicopathological variables and survival. A
      subgroup of the patients had weak or no expression of Cx43 in tumors. Loss of
      Cx43 expression was significantly correlated with shorter relapse-free and
      overall survival. Loss of Cx43 further identified a high-risk subgroup among
      stage I and stage II patients with reduced relapse-free and overall survival.
      Ectopic expression of Cx43 in the colon cancer cell line HT29 was associated with
      reduced growth in monolayer and soft agar cultures and in tumor xenografts. Cx43
      was found to colocalize with beta-catenin and negatively regulate the Wnt
      signaling pathway, and expression of Cx43 was associated with increased levels of
      apoptosis. Altogether, these data indicate that Cx43 is a colorectal cancer tumor
      suppressor protein that predicts clinical outcome.

PMID- 21866552
TI  - Paraptosis accompanied by autophagy and apoptosis was induced by celastrol, a
      natural compound with influence on proteasome, ER stress and Hsp90.
AB  - In the present study, we found that celastrol, a natural compound with well-known
      apoptosis-inducing effect, could also induce paraptosis-like cytoplasmic
      vacuolization in cancer cell lines including HeLa cells, A549 cells and PC-3
      cells derived from cervix, lung and prostate, respectively. Further study using
      HeLa cells indicated that the vacuoles induced by celastrol might be derived from
      dilation of endoplasmic reticulum. And, in celastrol-treated cells, markers of
      autophagy such as transformation of microtubule-associated protein 1 light chain
      3 (LC3)I to LC3II and LC3 punctates formation were identified. Interestingly,
      autophagy inhibitors could not interrupt but enhance the induction of cytoplasmic
      vacuolization. Furthermore, MAPK pathways were activated by celastrol and
      inhibitors of MEK and p38 pathways could prevent the formation of cytoplasmic
      vacuolization. Celastrol treatment also induced G2/M cell cycle arrest and
      apoptosis in HeLa cells. In conclusion, celastrol induced a kind of paraptosis
      accompanied by autophagy and apoptosis in cancer cells. The coincidence of
      apoptosis and autophagy together with paraptosis might contribute to the unique
      characteristics of paraptosis in celastrol-treated cells such as the dependence
      of paraptosis on MAPK pathways and dynamic change of LC3 proteins. Both
      paraptosis and apoptosis could contribute to the cell death induced by celastrol
      while autophagy might serve as a kind of survival mechanism. The potency of
      celastrol to induce paraptosis, apoptosis and autophagy at the same dose might be
      related to its capability to affect a variety of pathways including proteasome,
      ER stress and Hsp90.

PMID- 21866553
TI  - Constitutively active PTH/PTHrP receptor specifically expressed in osteoblasts
      enhances bone formation induced by bone marrow ablation.
AB  - Bone is maintained by continuous bone formation by osteoblasts provided by
      proliferation and differentiation of osteoprogenitors. Parathyroid hormone (PTH)
      activates bone formation, but because of the complexity of cells in the
      osteoblast lineage, how these osteoprogenitors are regulated by PTH in vivo is
      incompletely understood. To elucidate how signals by PTH in differentiated
      osteoblasts regulate osteoprogenitors in vivo, we conducted bone marrow ablation
      using Col1a1-constitutively active PTH/PTHrP receptor (caPPR) transgenic mice.
      These mice express caPPR specifically in osteoblasts by using 2.3 kb Col1a1
      promoter and showed higher trabecular bone volume under steady-state conditions.
      In contrast, after bone marrow ablation, stromal cells recruited from bone
      surface extensively proliferated in the marrow cavity in transgenic mice,
      compared to limited proliferation in wild-type mice. Whereas de novo bone
      formation was restricted to the ablated area in wild-type mice, the entire marrow
      cavity, including not only ablated area but also outside the ablated area, was
      filled with newly formed bone in transgenic mice. Bone mineral density was
      significantly increased after ablation in transgenic mice. Bone marrow cell
      culture in osteogenic medium revealed that alkaline phosphatase-positive area was
      markedly increased in the cells obtained from transgenic mice. Furthermore, mRNA
      expression of Wnt-signaling molecules such as LRP5, Wnt7b, and Wnt10b were
      upregulated after marrow ablation in bone marrow cells of transgenic mice. These
      results indicate that constitutive activation of PTH/PTHrP receptor in
      differentiated osteoblasts enhances bone marrow ablation-induced recruitment,
      proliferation, and differentiation of osteoprogenitors.

PMID- 21866554
TI  - Increased expression of insulin-like growth factor-1 receptor is correlated with
      tumor metastasis and prognosis in patients with osteosarcoma.
AB  - BACKGROUND: The aim of this study was to investigate the association of insulin
      like growth factor-1 receptor (IGF-1R) with metastasis and prognosis of
      osteosarcoma patients. METHODS: RT-PCR and Western blot assays were performed to
      detect IGF-1R mRNA and protein expression in 26 osteosarcoma and noncancerous
      bone tissues. Immunohistochemistry was performed to analyze the correlation of
      IGF-1R expression in 84 osteosarcoma tissues with clinicopathological factors or
      survival of patients. Lentivirus-mediated RNA interference system was employed to
      downregulate IGF-1R expression and analyze the effects of IGF-1R downregulation
      on invasion and metastasis of osteosarcoma cells. RESULTS: The relative levels of
      IGF-1R mRNA and protein expression were significantly higher in osteosarcoma
      tissues than in corresponding noncancerous bone tissues. The expression of IGF-1R
      protein was closely associated with surgical stage and distant metastasis of
      osteosarcoma patients. Osteosarcoma patients with high IGF-1R expression had
      poorer survival, and multivariate Cox analyses showed that high IGF-1R expression
      was an independent prognostic maker. Lentivirus-mediated targeting IGF-1R could
      significantly inhibit adhesion, migration, invasion, and metastasis of
      osteosarcoma cells, which might be correlated with of inactivation of Akt
      signaling pathway. CONCLUSIONS: IGF-1R is an independent prognostic marker for
      osteosarcoma patients and increased expression of this molecular is correlated
      with metastasis of osteosarcoma.

PMID- 21866555
TI  - Modeling the bullying prevention program design recommendations of students from
      grades five to eight: a discrete choice conjoint experiment.
AB  - We used a discrete choice conjoint experiment to model the bullying prevention
      recommendations of 845 students from grades 5 to 8 (aged 9-14). Students made
      choices between experimentally varied combinations of 14 four-level prevention
      program attributes. Latent class analysis yielded three segments. The high impact
      segment (27.1%) recommended uniforms, mandatory recess activities, four
      playground supervisors, surveillance cameras, and 4-day suspensions when students
      bully. The moderate impact segment (49.5%) recommended discretionary uniforms and
      recess activities, four playground supervisors, and 3-day suspensions.
      Involvement as a bully or bully-victim was associated with membership in a low
      impact segment (23.4%) that rejected uniforms and surveillance cameras. They
      recommended fewer anti-bullying activities, discretionary recess activities,
      fewer playground supervisors, and the 2-day suspensions. Simulations predicted
      most students would recommend a program maximizing student involvement combining
      prevention with moderate consequences. The simulated introduction of mandatory
      uniforms, surveillance cameras, and long suspensions reduced overall support for
      a comprehensive program, particularly among students involved as bullies or bully
      victims.

PMID- 21866556
TI  - In situ metal tip sharpening of scanning probe microscopes.
AB  - This article demonstrated a new approach for fabrication and sharpening of metal
      tips of scanning probe microscopes. Experimentally, a metal tip was heated and
      melted by a focused laser light. The tip was then sharpened by a strong electric
      field and consolidated as the laser was turned off. With a low-vacuum and a high
      voltage source, a 25-um indium-coated platinum wire was sharpened to a tip with
      diameters below 50 nm. The minimal tip radius by this method is estimated to be
      below 1 nm. With this technique, in situ tip sharpening for SPM would be
      possible.

PMID- 21866557
TI  - Application of lyophilization to prepare the nitrifying bacterial biofilm for
      imaging with scanning electron microscopy.
AB  - Structure of bacterial biofilms may be investigated using several variants of
      scanning electron microscopy (SEM). We apply lyophilization to prepare nitrifying
      bacterial biofilm for conventional SEM imaging in high-vacuum mode (CSEM). We
      therefore replace standard biofilm fixation in glutaraldehyde cross-linking,
      ethanol dehydration, and critical-point drying (CPD) with less-invasive low
      temperature drying by sublimation in vacuum. We compare this approach with: (1)
      standard preparation with glutaraldehyde fixation, ethanol dehydration, and CPD
      before CSEM, (2) cryo-sputter preparation of rapidly frozen biofilm in hydrated
      state (cryo-SEM), and (3) in situ observation without any sample pretreatment in
      environmental SEM. Combined imaging with these modalities revealed two distinct
      immobilization patterns on the polyurethane foam: (1) large irregular aggregates
      (flocs) of bacterial biofilm that exist as irregular biofilm fragments, rope-like
      structures, or biofilm layers on the foam surface; (2) biofilm threads adherent
      to the surface of polyurethane foam. Our results indicate that lyophilization was
      suitable for preservation of bacterial cells and many forms of structure of
      extracellular matrix. The lyophilized material could be imaged with high
      resolution (using CSEM) to generate structural information complementary to that
      obtained with other SEM techniques.

PMID- 21866558
TI  - Quantitative characterization of the mesothelioma-inducing erionite series
      minerals by transmission electron microscopy and energy dispersive spectroscopy.
AB  - Air-collected erionite series minerals from Cappadocia region of Turkey were
      characterized quantitatively by using transmission electron microscopy (TEM)
      equipped with energy dispersive spectroscopy (EDS). Field emission scanning
      electron microscopy aided identification of fibrous minerals. Quantitative
      characterization guidelines for positive identification of erionites proposed by
      Dogan and Dogan (2008) was applied and the modified balance error formula (E%<10)
      and Mg-content test <0.80 were performed for each analysis. Erionite species
      computation showed that the mineral is erionite-K and a mean chemical formula is
      proposed based upon the TEM-EDS results. Among the 60 analyses, 11 passed E% test
      (18.3%), 33 passed Mg-content test (55.0%), and only 3 passed both E% and Mg
      content tests (5.0%). This shows difficulty of quantitative characterization of
      the erionite series minerals. However, as erionite is the most carcinogenic
      mineral known and is classified by IARC as a Group-I (human) carcinogen, it
      requires special attention from the mineralogical community to help establish its
      true mineralogical properties. Quantitatively characterized erionite data are
      very scarce in literature. Correctly identified erionite mineral types will be
      useful to medical researchers in their search to find a possible cure for the
      deadly disease of mesothelioma.

PMID- 21866559
TI  - Highly accurate SNR measurement using the covariance of two SEM images with the
      identical view.
AB  - Quality of an SEM image is strongly influenced by the extent of noise. As a well
      known method in the field of SEM, the covariance is applied to measure the signal
      to-noise ratio (SNR). This method has potential ability for highly accurate
      measurement of the SNR, which is hardly known until now. If the precautions
      discussed in this article are adopted, that method can demonstrate its real
      ability. These precautions are strongly related to "proper acquisition of two
      images with the identical view," "alignment of an aperture diaphragm," "reduction
      of charging phenomena," "elimination of particular noises," and "accurate
      focusing," As necessary, characteristics in SEM signal and noise are investigated
      from a few standpoints. When using the maximum performance of this measurement,
      SNR of many SEM images obtained in a variety of the SEM operating conditions and
      specimens can be measured accurately.

PMID- 21866561
TI  - Waking up to narcolepsy.

PMID- 21866560
TI  - Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in
      China.
AB  - OBJECTIVE: Narcolepsy is caused by the loss of hypocretin/orexin neurons in the
      hypothalamus, which is likely the result of an autoimmune process. Recently,
      concern has been raised over reports of narcolepsy in northern Europe following
      H1N1 vaccination. METHODS: The study is a retrospective analysis of narcolepsy
      onset in subjects diagnosed in Beijing, China (1998-2010). Self-reported month
      and year of onset were collected from 629 patients (86% children). Graphical
      presentation, autocorrelations, chi-square, and Fourier analysis were used to
      assess monthly variation in onset. Finally, 182 patients having developed
      narcolepsy after October 2009 were asked for vaccination history. RESULTS: The
      occurrence of narcolepsy onset was seasonal, significantly influenced by month
      and calendar year. Onset was least frequent in November and most frequent in
      April, with a 6.7-fold increase from trough to peak. Studying year-to-year
      variation, we found a 3-fold increase in narcolepsy onset following the 2009 H1N1
      winter influenza pandemic. The increase is unlikely to be explained by increased
      vaccination, as only 8 of 142 (5.6%) patients recalled receiving an H1N1
      vaccination. Cross-correlation indicated a significant 5- to 7-month delay
      between the seasonal peak in influenza/cold or H1N1 infections and peak in
      narcolepsy onset occurrences. INTERPRETATION: In China, narcolepsy onset is
      highly correlated with seasonal and annual patterns of upper airway infections,
      including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was
      phase delayed by 6 months relative to winter H1N1 infections, and the correlation
      was independent of H1N1 vaccination in the majority of the sample.

PMID- 21866562
TI  - Anti-apoptotic protection afforded by cardioplegic celsior and histidine buffer
      solutions to hearts subjected to ischemia and ischemia/reperfusion.
AB  - Cardiomyocytes undergo apoptosis in response to ischemia and ischemia/reperfusion
      (I/R). During heart preservation, inhibition of apoptosis is critical to avoid
      organ failure. We aimed to compare the protection afforded by Celsior (Cs) and
      Histidine buffer solution (HBS) against apoptotic signaling in hearts subjected
      to moderate (4 h) versus severe (6 h) ischemia alone or followed by 30 min
      reperfusion. The impact of gender on cardioplegic protection was also explored.
      Hearts from male and female Wistar-Han rats were divided by gender in distinct
      groups: control, perfusion_control, ischemia, and I/R. Ischemia and I/R groups
      were divided in subgroups Cs or HBS, and subjected to 4 or 6 h ischemia alone or
      followed by reperfusion. Proteins involved in apoptotic signaling (p53, Bax, Fas,
      FasL, and Flip) were quantified by Western blot in mitochondria and/or whole
      tissue. Caspases 3, 8, and 9-like activities were measured and hemodynamic
      parameters were monitored. Ischemia activated p53/Bax signaling. After I/R, HBS
      preserved hearts had lower p53/Bax content in mitochondrial fractions than Cs
      preserved hearts. The p53/Bax decrease in tissue samples was mostly observed in
      females. Caspase 3-like activity was increased in HBS-preserved male hearts. The
      heart rate was decreased in Cs and HBS-preserved hearts. Fas protein levels
      remained unaltered in all conditions but soluble FasL increased from 4 to 6 h
      preservation in Cs and HBS. Hearts from male rats were more prone to apoptosis
      and myocardial dysfunction. HBS and Cs were not effective in inhibiting apoptotic
      signaling although HBS presented best overall results. Both solutions should be
      improved to prevent apoptosis and myocardial dysfunction after I/R.

PMID- 21866563
TI  - Hypoxia induces peroxisome proliferator-activated receptor alpha (PPARalpha) and
      lipid metabolism peroxisomal enzymes in human glioblastoma cells.
AB  - Glioblastoma multiforme (GBM) represents the most severe type of glioma, the most
      common brain tumor. Their malignancy shows a relationship with an increased
      proliferation and a poorly organized tumor vascularization, an event that leads
      to inadequate blood supply, hypoxic areas and at last to the formation of
      necrotic areas, a feature of glioblastoma. Hypoxic/necrotic tumors are more
      resistant to chemotherapy and radiation therapies, thus it is crucial to
      formulate new therapeutic approaches that can render these tumors more sensitive
      to the action of conventional therapies. It has been demonstrated that under
      hypoxia, gliomas accumulate lipid droplets and that this event is positively
      correlated with the degree of malignancy, glioblastoma being the most endowed
      with lipid droplets. We have previously demonstrated in ex vivo glioma specimens
      a grade-dependent lipid metabolism perturbation. Here we studied the lipid
      pathways and the presence of stemness markers in glioma primary cultures,
      obtained from surgical specimens of patients affected by glioma at different
      grade of malignancy, GBM primary cultures cultured under both hypoxic and
      normoxic conditions, as well as normal human astrocytes. The results obtained
      demonstrate that hypoxia plays a crucial role in regulating the expression of
      lipid metabolism peroxisomal enzymes, the lipid droplets accumulation as well as
      the transcription factor PPARalpha.

PMID- 21866564
TI  - Lrp5 and Lrp6 play compensatory roles in mouse intestinal development.
AB  - Low-density lipoprotein receptor-related proteins 5 and 6 (Lrp5 and Lrp6) are co
      receptors of Wnt ligands and play important roles in Wnt/beta-catenin signal
      transduction. Mice homozygous for a germline deletion of Lrp6 die at birth with
      several associated defects, while Lrp5-deficient mice are viable. Here, we
      conditionally deleted Lrp5 and/or Lrp6 in the mouse gut ((gut-/-)) by crossing
      mice carrying floxed alleles of Lrp5 and Lrp6 to a strain expressing Cre
      recombinase from the villin promoter (villin-Cre). The changes in morphology,
      differentiation, and Wnt signal transduction were validated using
      immunohistochemistry and other staining. Consistent with observations in mice
      carrying a homozygous germline deletion in Lrp5, intestinal development in
      Lrp5(gut-/-) mice was normal. In addition, mice homozygous for villin-Cre-induced
      deletion of Lrp6 (Lrp6(gut-/-)) were viable with apparently normal intestinal
      differentiation and function. However, mice homozygous for villin-Cre inactivated
      alleles of both genes (Lrp5(gut-/-) ; Lrp6(gut-/-)) died within 1 day of birth.
      Analysis of embryonic Lrp5(gut-/-); Lrp6(gut-/-) intestinal epithelium showed a
      progressive loss of cells, an absence of proliferation, and a premature
      differentiation of crypt stem/precursor cells; no notable change in
      differentiation was observed in the embryos lacking either gene alone. Further
      immunohistochemical studies showed that expression of the Wnt/beta-catenin
      target, cyclin D1, was specifically reduced in the intestinal epithelium of
      Lrp5(gut-/-); Lrp6(gut-/-) embryos. Our data demonstrate that Lrp5 and Lrp6 play
      redundant roles in intestinal epithelium development, and that Lrp5/6 might
      regulate intestinal stem/precursor cell maintenance by regulating Wnt/beta
      catenin signaling.

PMID- 21866565
TI  - Direct modulation of the protein kinase A catalytic subunit alpha by growth
      factor receptor tyrosine kinases.
AB  - The cyclic-AMP-dependent protein kinase A (PKA) regulates processes such as cell
      proliferation and migration following activation of growth factor receptor
      tyrosine kinases (RTKs), yet the signaling mechanisms that link PKA with growth
      factor receptors remain largely undefined. Here we report that RTKs can directly
      modulate the function of the catalytic subunit of PKA (PKA-C) through post
      translational modification. In vitro kinase assays revealed that both the
      epidermal growth factor and platelet derived growth factor receptors (EGFR and
      PDGFR, respectively) tyrosine phosphorylate PKA-C. Mass spectrometry identified
      tyrosine 330 (Y330) as a receptor-mediated phosphorylation site and mutation of
      Y330 to phenylalanine (Y330F) all but abolished the RTK-mediated phosphorylation
      of PKA-C in vitro. Y330 resides within a conserved region at the C-terminal tail
      of PKA-C that allosterically regulates enzymatic activity. Therefore, the effect
      of phosphorylation at Y330 on the activity of PKA-C was investigated. The K(m)
      for a peptide substrate was markedly decreased when PKA-C subunits were tyrosine
      phosphorylated by the receptors as compared to un-phosphorylated controls.
      Importantly, tyrosine-phosphorylated PKA-C subunits were detected in cells
      stimulated with EGF, PDGF, and Fibroblast growth factor 2 (FGF2) and in
      fibroblasts undergoing PDGF-mediated chemotaxis. These results demonstrate a
      direct, functional interaction between RTKs and PKA-C and identify tyrosine
      phosphorylation as a novel mechanism for regulating PKA activity.

PMID- 21866567
TI  - MURF1 deficiency suppresses unloading-induced effects on osteoblasts and
      osteoclasts to lead to bone loss.
AB  - Loss of mechanical stress or unloading causes disuse osteoporosis that leads to
      fractures and deteriorates body function and affects mortality rate in aged
      population. This bone loss is due to reduction in osteoblastic bone formation and
      increase in osteoclastic bone resorption. MuRF1 is a muscle RING finger protein
      which is involved in muscle wasting and its expression is enhanced in the muscle
      of mice subjected to disuse condition such as hind limb unloading (HU). However,
      whether MuRF1 is involved in bone loss due to unloading is not known. We
      therefore examined the effects of MuRF1 deficiency on unloading-induced bone
      loss. We conducted hind limb unloading of MuRF1 KO mice and wild-type control
      mice. Unloading induced about 60% reduction in cancellous bone volume (BV/TV) in
      WT mice. In contrast, MuRF1 deficiency suppressed unloading-induced cancellous
      bone loss. The cortical bone mass was also reduced by unloading in WT mice. In
      contrast, MuRF1 deficiency suppressed this reduction in cortical bone mass. To
      understand whether the effects of MuRF1 deficiency suppress bone loss is on the
      side of bone formation or bone resorption, histomorphometry was conducted.
      Unloading reduced bone osteoblastic formation rate (BFR) in WT. In contrast,
      MuRF1 deficiency suppressed this reduction. Regarding bone resorption, unloading
      increased osteoclast number in WT. In contrast, MURF1 deficiency suppressed this
      osteoclast increase. These data indicated that the ring finger protein, MURF1 is
      involved in disuse-induced bone loss in both of the two major bone remodeling
      activities, osteoblastic bone formation and osteoclastic bone resorption.

PMID- 21866568
TI  - Selenoprotein W depletion induces a p53- and p21-dependent delay in cell cycle
      progression in RWPE-1 prostate epithelial cells.
AB  - The anticancer activity of selenium (Se) has been demonstrated in myriad animal
      and in vitro studies, yet the mechanisms remain obscure. The main form of Se in
      animal tissues is selenocysteine in selenoproteins, but the relative importance
      of selenoproteins versus smaller Se compounds in cancer protection is unresolved.
      Selenoprotein W (SEPW1) is a highly conserved protein ubiquitously expressed in
      animals, bacteria, and archaea. SEPW1 depletion causes a delay in cell cycle
      progression at the G1/S transition of the cell cycle in breast and prostate
      epithelial cells. Tumor suppressor protein p53 is a master regulator of cell
      cycle progression and is the most frequently mutated gene in human cancers. p53
      was increased in SEPW1 silenced cells and was inversely correlated with SEPW1
      mRNA in cell lines with altered SEPW1 expression. Silencing SEPW1 decreased
      ubiquitination of p53 and increased p53 half-life. SEPW1 silencing increased
      p21(Cip1/WAF1/CDKN1A), while p27 (Kip1/CDKN1B) levels were unaffected. G1-phase
      arrest from SEPW1 knockdown was abolished by silencing p53 or p21. Cell cycle
      arrest from SEPW1 silencing was not associated with activation of ATM or
      phosphorylation of Ser-15 in p53, suggesting the DNA damage response pathway was
      not involved. Silencing GPX1 had no effect on cell cycle, suggesting that G1
      phase arrest from SEPW1 silencing was not due to loss of antioxidant protection.
      More research is required to identify the function of SEPW1 and how it affects
      stability of p53.

PMID- 21866566
TI  - Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: reduction
      of Wnt-associated proteins and reduced translocation of galectin-3-mediated beta
      catenin to the nucleus.
AB  - The cucurbitacins are tetracyclic triterpenes found in plants of the family
      Cucurbitaceae. Cucurbitacins have been shown to have anti-cancer and anti
      inflamatory activities. We investigated the anti-cancer activity of cucurbitacin
      B extracted from Thai medicinal plant Trichosanthes cucumerina Linn. Cell
      viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay. Results indicated that cucurbitacin B from T.
      cucumerina Linn. has a cytotoxic effect on breast cancer cell lines SKBR-3 and
      MCF-7 with an IC50 of 4.60 and 88.75 ug/ml, respectively. Growth inhibition was
      attributed to G2/M phase arrest and apoptosis. Cyclin D1, c-Myc, and beta-catenin
      expression levels were reduced. Western blot analysis showed increased PARP
      cleavage and decreased Wnt-associated signaling molecules beta-catenin, galectin
      3, cyclin D1 and c-Myc, and corresponding changes in phosphorylated GSK-3beta
      levels. Cucurbitacin B treatment inhibited translocation to the nucleus of beta
      catenin and galectin-3. The depletion of beta-catenin and galectin-3 in the
      nucleus was confirmed by cellular protein fractionation. T-cell factor
      (TCF)/lymphoid enhancer factor (LEF)-dependent transcriptional activity was
      disrupted in cucurbitacin B treated cells as tested by a TCF reporter assay. The
      relative luciferase activity was reduced when we treated cells with cucurbitacin
      B compound for 24 h. Our data suggest that cucurbitacin B may in part induce
      apoptosis and exert growth inhibitory effect via interruption the Wnt signaling.

PMID- 21866570
TI  - Monitoring the gestation period of rescued Formosan pangolin (Manis pentadactyla
      pentadactyla) with progesterone radioimmunoassay.
AB  - Eight species of pangolin have been identified in the world. However,
      understanding of pangolin reproductive biology has been limited to fragmentary
      records. In this study, the concentration of serum progesterone in three pregnant
      and two nonpregnant rescued female Formosan pangolins (Manis pentadactyla
      pentadactyla) was monitored using a commercial progesterone radioimmunoassay kit.
      During gestation, the serum progesterone of pregnant pangolins A, B, and C
      remained at 28.5-55 ng/ml (n = 31 samples), 10.9-50.1 ng/ml (n = 34), and 12.4
      and 33.5 ng/ml with a peak at 47.6 ng/ml (n = 19), respectively, whereas the
      serum progesterone of nonpregnant pangolins D and E remained at 1.99 +/- 1.62
      ng/ml (n = 80) and 2.27 +/- 1.64 ng/ml (n = 27), respectively. From this study,
      it was found that female pangolin weighing as low as 2.14 kg was already capable
      of reproduction. For pregnant pangolins to give birth to viable offspring, their
      body weight must increase significantly, 63.89 and 134.0% in the study, from the
      time of inception or early pregnancy until parturition. In addition, study has
      found that both viable offspring were born fully developed and exceeded 80 g in
      weight. The period of gestation was found to be as short as 318 or longer than
      372 days. Therefore, the Formosan pangolin should only be able to reproduce once
      a year. This study is the first insight into hormone assay for determining the
      gestation period of pangolin. Further investigations on the same subject are
      necessary to establish criteria for the recognition of reproductive status in
      pangolins.

PMID- 21866571
TI  - Differences in carotenoid accumulation among three feeder-cricket species:
      implications for carotenoid delivery to captive insectivores.
AB  - There are a limited number of feeder-invertebrates available to feed captive
      insectivores, and many are deficient in certain nutrients. Gut-loading is used to
      increase the diversity of nutrients present in the captive insectivore diet;
      however, little is known about delivery of carotenoids via gut-loading.
      Carotenoids may influence health and reproduction due to their roles in immune
      and antioxidant systems. We assessed interspecific variation in carotenoid
      accumulation and retention in three feeder-cricket species (Gryllus bimaculatus,
      Gryllodes sigillatus and Acheta domesticus) fed one of three diets (wheat-bran,
      fish-food based formulated diet, and fresh fruit and vegetables). Out of the
      three species of feeder-cricket in the fish-food-based dietary treatment group,
      G. bimaculatus had the greatest total carotenoid concentration. All cricket
      species fed the wheat-bran diet had very low carotenoid concentrations. Species
      on the fish-food-based diet had intermediate carotenoid concentrations, and those
      on the fruit and vegetable diet had the highest concentrations. Carotenoid
      retention was poor across all species. Overall, this study shows that, by
      providing captive insectivores with G. bimaculatus crickets recently fed a
      carotenoid-rich diet, the quantity of carotenoids in the diet can be increased.

PMID- 21866569
TI  - The basic helix loop helix transcription factor Twist1 is a novel regulator of
      ATF4 in osteoblasts.
AB  - Parathyroid hormone (PTH) is an essential regulator of endochondral bone
      formation and an important anabolic agent for the reversal of bone loss. PTH
      mediates its functions in part by regulating binding of the bone-related
      activating transcription factor 4 (ATF4) to the osteoblast-specific gene,
      osteocalcin. The basic helix-loop-helix (bHLH) factors Twist1 and Twist2 also
      regulate osteocalcin transcription in part through the interaction of the C
      terminal "box" domain in these factors and Runx2. In this study, we discovered a
      novel function of PTH: its ability to dramatically decrease Twist1 transcription.
      Since ATF4 is a major regulator of the PTH response in osteoblasts, we assessed
      the mutual regulation between these factors and determined that Twist proteins
      and ATF4 physically interact in a manner that affects ATF4 DNA binding function.
      We mapped the interaction domain of Twist proteins to the C-terminal "box" domain
      and of ATF4, to the N-terminus. Furthermore, we demonstrate that Twist1
      overexpression in osteoblasts attenuates ATF4 binding to the osteocalcin promoter
      in response to PTH. This study thus identifies Twist proteins as novel inhibitory
      binding partners of ATF4 and explores the functional significance of this
      interaction.

PMID- 21866572
TI  - The influence of Co-Cr and UHMWPE particles on infection persistence: an in vivo
      study in mice.
AB  - Wear of metal-on-metal (cobalt-chromium, Co-Cr particles) and metal-on
      polyethylene (ultra-high-molecular-weight polyethylene, UHMWPE particles) bearing
      surfaces in hip prostheses is a major problem in orthopedics. This study aimed to
      compare the influence of Co-Cr and UHMWPE particles on the persistence of
      infection. Bioluminescent Staphylococcus aureus Xen36 were injected in air
      pouches prepared in subcutaneous tissue of immuno-competent BALB/c mice
      (control), as a model for the joint space, in the absence or presence of Co-Cr or
      UHMWPE particles. Bioluminescence was monitored longitudinally up to 21 days,
      corrected for absorption and reflection by the particles and expressed relative
      to the bioluminescence found in the presence of staphylococci only. After
      termination, air pouch fluid and air pouch membrane were cultured and
      histologically analyzed. Bioluminescence was initially lower in mice exposed to
      UHMWPE particles with staphylococci than in mice injected with staphylococci
      only, possibly because UHMWPE particles initially stimulated a higher macrophage
      presence in murine air pouch membranes. For mice exposed to Co-Cr particles with
      staphylococci, bioluminescence was observed to be higher in two out of six
      animals compared to the presence of staphylococci alone. In the majority of mice,
      infection risk in the absence or presence of Co-Cr and UHMWPE particles appeared
      similar, assuming that the longevity of an elevated bioluminescence is indicative
      of a higher infection risk. However, the presence of Co-Cr particles yielded a
      higher bioluminescence in two out of six mice, possibly because the macrophage
      degradative function was hampered by the presence of Co-Cr particles.

PMID- 21866574
TI  - Effect of sialodacryoadenitis virus infection on axonal regeneration.
AB  - The effect of sialodacryoadenitis virus (SDAV) infection on axonal regeneration
      and functional recovery was investigated in male Lewis rats. Animals underwent
      unilateral tibial nerve transection, immediate repair, and treatment with either
      FK506 (treated) or control vehicle (untreated). Serial walking track analyses
      were performed to assess functional recovery. Nerves were harvested for
      morphometric analysis on postoperative day 18 after an SDAV outbreak occurred
      that affected the 12 experimental animals. Histomorphometry and walking track
      data were compared against 36 historical controls. Rats infected with SDAV
      demonstrated severely impaired axonal regeneration and diminished functional
      recovery. Total fiber counts, nerve density, and percent neural tissue were all
      significantly reduced in infected animals (P < 0.05). Active SDAV infection
      severely impaired nerve regeneration and negated the positive effect of FK506 on
      nerve regeneration in rats. Immunosuppressive risks must be weighed carefully
      against the potential neuroregenerative benefits in the treatment of peripheral
      nerve injuries.

PMID- 21866573
TI  - Regenerative potential of TGFbeta3 + Dex and notochordal cell conditioned media
      on degenerated human intervertebral disc cells.
AB  - Injection of soluble cell signaling factors into degenerated intervertebral discs
      (IVDs) offers a minimally invasive treatment that could limit the processes of
      degeneration by stimulating native matrix repair. This study evaluated the
      regenerative capacity of degenerated nucleus pulposus (NP) cells obtained from
      patients undergoing anterior interbody fusions by measuring metabolic activity,
      DNA content, glycosaminoglycan (GAG) content, and cellular phenotype using qRT
      PCR profiling with a custom array of 42 genes. NP cells were cultured in alginate
      for 7 days with 4 treatment groups: transforming growth factor beta 3 (TGFbeta3)
      + dexamethasone (Dex), soluble factors released from notochordal cells (NCs)
      cultured in alginate (NCA), soluble factors released from NCs in their native
      tissue environment (NCT), and basal media. TGFbeta3 + Dex stimulated degenerated
      human NP cells to proliferate and exhibit an anti-catabolic gene expression
      profile (with a decrease in ADAMTS5 and MMP1 compared to basal, and an increase
      in SOX9, decrease in ADAMTS5, MMP1, collagen I and collagen III compared to day
      0), while NCA stimulated the greatest GAG per cell. We conclude that degenerated
      human NP cells exhibit regenerative potential, and that an optimal treatment will
      likely require treatments, such as TGFbeta3 + Dex, which were able to increase
      cell metabolism and reduce catabolism, as well as treatments with factors found
      in NC conditioned medium, that were able to produce high amounts of GAG per cell.
      Additional studies to optimize NC culture conditions are required to determine if
      NC conditioned medium can be made with the capacity to enhance NP cell
      proliferation and metabolism.

PMID- 21866575
TI  - Stepwise construction of Au4Ag2Cu2 coinage rings supported by linear
      tetraphosphine ligands.

PMID- 21866576
TI  - Selective targeting of fluorescent nanoparticles to proteins inside live cells.

PMID- 21866577
TI  - Gold(I)-catalyzed synthesis of benzoxocines by an 8-endo-dig cyclization.

PMID- 21866578
TI  - Conduction mechanisms and environmental sensitivity of solution-processed silicon
      nanoparticle layers for thin-film transistors.

PMID- 21866579
TI  - A series of hyperbranched polytriazoles containing perfluoroaromatic rings from
      AB2-type monomers: convenient syntheses by click chemistry under copper(I)
      catalysis and enhanced optical nonlinearity.
AB  - In this paper, four new hyperbranched polytriazoles containing azo moieties,
      derived from different AB(2) -type monomers, were successfully prepared through
      the "click" chemistry reaction under copper(I) catalysis by modifying the
      synthetic route. The polymers were soluble in organic solvents and exhibited good
      second-order nonlinear optical (NLO) properties. Thanks to the self-assembly of
      perfluoroaromatic moieties in the periphery, HP2 showed the best NLO properties,
      with the d(33) value as high as 145.0 pm V(-1).

PMID- 21866580
TI  - Chemical technologies for exploiting and recycling carbon dioxide into the value
      chain.
AB  - While experts in various fields discuss the potential of carbon capture and
      storage (CCS) technologies, the utilization of carbon dioxide as chemical
      feedstock is also attracting renewed and rapidly growing interest. These
      approaches do not compete; rather, they are complementary: CCS aims to capture
      and store huge quantities of carbon dioxide, while the chemical exploitation of
      carbon dioxide aims to generate value and develop better and more-efficient
      processes from a limited part of the waste stream. Provided that the overall
      carbon footprint for the carbon dioxide-based process chain is competitive with
      conventional chemical production and that the reaction with the carbon dioxide
      molecule is enabled by the use of appropriate catalysts, carbon dioxide can be a
      promising carbon source with practically unlimited availability for a range of
      industrially relevant products. In addition, it can be used as a versatile
      processing fluid based on its remarkable physicochemical properties.

PMID- 21866581
TI  - Gravity-related critical periods in vestibular and tail development of Xenopus
      laevis.
AB  - Sensory systems are characterized by developmental periods during which they are
      susceptible to environmental modifications, in particular to sensory deprivation.
      The experiment, XENOPUS, on Soyuz in 2008 was the fourth space flight experiment
      since 1993 to explore whether tail and vestibular development of Xenopus laevis
      has a gravity-related critical period. During this flight, tadpoles were used
      that had developed either the early hindlimb (stage 47) or forelimb bud (stage
      50) at launch of the spacecraft. The results revealed (1) no impact of
      microgravity on the development of the roll-induced vestibuloocular reflex (rVOR)
      in both stages and (2) a stage-related sensitivity of tail development to
      microgravity exposure. These results were combined and compared with observations
      from space flights on other orbital platforms. The combined data revealed (1) a
      narrow gravity-related critical period for rVOR development close to the period
      of the first appearance of the reflex and (2) a longer one for tail development
      lasting from the early tail bud to the early forelimb bud stage.

PMID- 21866582
TI  - US physicians urge end to unnecessary stent operations.

PMID- 21866583
TI  - Laos builds specialty training system through partnerships.

PMID- 21866584
TI  - Unexpected life lessons from cardiac anatomy and physiology.

PMID- 21866585
TI  - Retraction notice to "Pulsus paradoxus; historical and clinical perspectives"
      [International Journal of Cardiology 138 (2010) 229-232].

PMID- 21866586
TI  - Federal funding for stem cell research:  15 years of indecision.

PMID- 21866587
TI  - Leishman-Donovan bodies in the bone marrow biopsy.

PMID- 21866588
TI  - Teaching molecular medicine within medical education: no time to wait.

PMID- 21866589
TI  - Medicine and the humanities in medical school curricula.

PMID- 21866590
TI  - Controlled delivery of ranitidine in the stomach using magnetic field.
AB  - An attempt has been made to localize ranitidine loaded microspheres in the
      stomach by magnetic means. Since ranitidine undergoes metabolism by microbial
      enzymes in the intestine, it is ideal to localize the controlled drug delivery
      system within the stomach to get uniform release and absorption of the drug for
      the desired period. Gelatin magnetic microspheres loaded with 9.1, 17.9, 26.3 and
      33.3% w/w of ranitidine hydrochloride were prepared by emulsification-cross
      linking technique. The formulated microspheres were characterized by magnetite
      content, particle size and in vitro drug release. The efficiency of microspheres
      to be localized in the stomach is tested in vivo in rats. The prepared
      microspheres were spherical and had a size distribution from 10 to 105 microm.
      The in vitro study revealed the capability of microspheres to release the drug
      over a period of 8 to 12 hours, depending on drug loading. The release was found
      to be diffusion controlled and followed fickian diffusion principle. The in vivo
      study showed the efficiency of microspheres to be retained in the stomach over a
      period of 8 hours.

PMID- 21866591
TI  - Lipoxygenase inhibitory tetraketones: potential remedial source for inflammation
      and asthma.
AB  - OBJECTIVE: A series of tetraketones has been synthesized by way of a one pot
      synthesis and screened for inhibitory activity against the enzyme lipoxygenase.
      METHOD: An efficient and high yielding one pot synthesis to tetraketones [2-22]
      has been developed by way of tetraethyl ammonium bromide (Et4N+Br-) mediated
      condensation of cyclohexane-1, 3-dione [1] with a variety of aldehydes.
      Lipoxygenase enzyme solution was prepared so that enzyme concentration in
      reaction mixture was adjusted to give rates of 0.05 absorbance/minute. The test
      compounds were prepared in methanol of concentrations 50, 25, 12.5, 6.25 and
      3.125 microM. The reaction mixture contained 160 microL (100 mM) sodium phosphate
      buffer (pH 8.0), 10 microL of test-compound solution and 20 microL of
      lipoxygenase solution. The contents were mixed and incubated for 10 minutes at 25
      degrees C. The reaction was then initiated by the addition of 10 microL substrate
      solution (linoleic acid, 0.5 mM, 0.12% w/v tween 20 in the ratio of 1:2), with
      the formation of (9Z, 11E)-(13S)-13-hydroperoxyoctadeca-9,11-dienoate, the change
      of absorbance at 234 nm was followed for 6 minutes. The concentrations of the
      test compounds that inhibited the lipoxygenase activity by 50% (IC50) were
      determined by monitoring the effect of increasing concentrations of these
      compounds in the assays on the degree of inhibition. The IC50 values were
      calculated by means of the EZ-Fit Enzyme-Kinetics Program (Perrella Scientific
      Inc., Amherst, U.S.A.). RESULT: The tetraketones [2-22] were synthesized in high
      yields (91-98%) using mild reaction conditions. Most of these compounds showed
      significant inhibitory activity against the enzyme lipoxygenase. It was found
      that the presence of substituents which increase delocalization of electrons
      enhances the inhibitory activity. CONCLUSION: It is concluded that the study is
      likely to lead to the discovery of therapeutically efficient agents against
      important disorders such as inflammation and asthma.

PMID- 21866592
TI  - Students admitted to university who fail: hidden disabilities affecting students'
      performance.
AB  - OBJECTIVE: To compare grade point averages and social adjustment and academic
      difficulties of students with or without a hidden disability at The University of
      the West Indies, Mona, Jamaica. METHODS: Comparison groups were identified
      through The University of the West Indies (UWI) Health Centre, peer-counselling
      training programme and an undergraduate class. The 165 participants completed a
      checklist on health, social and academic concerns and provided a copy of their
      transcripts. Students were screened for hidden disabilities including attention
      deficit hyperactivity disorder (ADHD) and psychiatric morbidity. RESULTS:
      Students with hidden disabilities consistently performed poorer academically than
      their non-disabled peers, and students with ADHD performed the worst. The high
      levels of distress common to students with a hidden disability may explain the
      difference in performance between them and non-disabled students.
      Students'ability to manage their time, irrespective of having a disability, was
      singled out as important for obtaining good grades. CONCLUSIONS: Potentially
      brilliant students are at risk of failing out of university because of hidden
      disabilities and the associated emotional and social challenges.

PMID- 21866593
TI  - HIV seroprevalence among male prison inmates in the six countries of the
      Organization of Eastern Caribbean states in the Caribbean (OECS).
AB  - OBJECTIVE: To determine HIV prevalence among male prison inmates in the six OECS
      countries in the Caribbean. SUBJECTS AND METHODS: Six unlinked, anonymous point
      prevalence surveys of a total of 1288 male inmates were conducted during a one
      year period, August 2004 - August 2005. An oral fluid sample was collected and an
      interviewer-administered questionnaire and consent form was completed for each
      survey participant. RESULTS: The overall HIV prevalence was 2.8% (range 2.0
      4.1%). Only 39% of all inmates had previously been tested, compared to 67% of the
      HIV-positive inmates. Of all inmates who previously tested, 61% had their last
      test less than two years ago, 45% had done so while in prison and 39% had done so
      in a hospital. Most of those who had not previously been tested had no particular
      reason for not doing so (57%); 24% of them felt it was not necessary or they were
      not at risk. CONCLUSION: HIV prevalence among male prison inmates was three times
      higher than the estimated OECS population prevalence in 2003, slightly higher
      than the prevalence among incarcerated males in the United States of America and
      Canada, and lower than that in other Caribbean countries in earlier years. Health
      information on prison populations is important as this is a vulnerable group,
      with frequent movement in and out of the general population. Preventative
      services, voluntary counselling and testing, and appropriate care and treatment
      should be available to all inmates as this is an opportunity for many who may not
      otherwise access these services.

PMID- 21866594
TI  - HIV testing and counselling for prevention of mother-to-child transmission at
      labour and delivery in Guyana.

PMID- 21866595
TI  - Seroprevalence of Leptospira in rattus norvegicus in Grenada, West Indies.
AB  - OBJECTIVE: To determine the seroprevalence of Leptospira and the serovars
      responsible for Leptospira exposure in rats in Grenada in order to assess rats as
      a reservoir host for human infection. DESIGN AND METHODS: Rattus norvegicus
      rodents were collected from each of the six parishes on the island of Grenada.
      Serum from 237 rats was tested by the microscopic agglutination test (MAT) and an
      Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA). Seroprevalence
      rates among parishes were compared using a chi-squared test of homogeneity.
      RESULTS: Of the 237 serum samples tested, 64 were positive by either MAT or ELISA
      for an overall seroprevalence of 27%. The ELISA identified 24.5% (57/233) of the
      rats positive at a titer of > or = 1:160. The MAT identified 7.1% (13/183) of the
      rats positive at a titer of > or = 1:100. Six of the 13 MAT positive samples had
      antibodies to multiple serovars. The serovars identified by the MAT with the
      greatest frequency were from the Icterohaemorrhagiae serogroup. Two rats had
      antibodies for serogroup Cynopteri, the first time this serogroup has been
      identified in Grenada. CONCLUSIONS: Our results for Leptospira exposure in rats
      in Grenada support R norvegicus as an important reservoir host for Leptospira,
      particularly those from the Icterohaemorrhagiae serogroup. Because this serogroup
      is the primary serogroup responsible for documented human exposure in Grenada,
      exposed rats represent a public health threat.

PMID- 21866596
TI  - Injury surveillance in Trinidad: an accident and emergency based injury
      surveillance system at the San Fernando General Hospital.
AB  - OBJECTIVE: Injuries are a significant cause of morbidity and mortality worldwide.
      Injuries disproportionately affect people living in low and middle income
      countries, including the Caribbean; however little is known about the
      epidemiology of injuries in these areas. An accident and emergency (A&E)
      department injury surveillance system was established at the San Fernando General
      Hospital, Trinidad and Tobago, to address this important data gap. METHODS: A
      detailed overview of the objectives, data collection methods, and inherent
      strengths and limitations of this surveillance system are presented, along with
      results of an analysis of data collected during the first three years of
      operations (from 2002 to 2004). RESULTS: Trained hospital staff collect a variety
      of injury/poisoning, demographic and clinical data on nearly 20,000 patients
      presenting each year with injury to the A&E Department. The total number of
      injuries in men was almost twice that in women. The majority of injuries were
      seen in those 25-44-years of age. Falls, other blunt force, stab/cut, traffic
      injury and poisoning represented the leading causes of injury. Nearly half of all
      the injuries occurred in the home, with the street/highway and work environments
      also accounting for an appreciable number of injuries. The majority of injuries
      were reported as unintentional. CONCLUSION: Injuries represent an important
      population health and health services issue in South Trinidad. Data from the A&E
      Department injury surveillance system represent an important resource to inform
      evidence-based health policy decisions on injury prevention and public health
      resource allocation.

PMID- 21866597
TI  - Adolescent ears: an avenue into their sexual and reproductive health values.
AB  - OBJECTIVES: This study sought to understand what sexual and reproductive health
      messages Jamaican adolescents get via Dancehall music and how themes in these
      messages can inform the development of a questionnaire for further exploration of
      the subject. METHOD: Qualitative processes: key informant interviews, content
      analysis and focus group discussions were used to identify the themes heard in
      Dancehall songs to which adolescents listen. Adolescent investigators were
      utilized to enhance the communication flow among their peers while the adult
      investigator coordinated the analysis process. The data generated by each method
      were analysed manually and the themes used to inform development of a
      quantitative questionnaire for further study. RESULTS: Of 43 songs identified by
      key informants, twenty-five were short-listed as Dancehall songs as they having
      met the criteria for conveying sexual and reproductive health and relationship
      themes. Most themes were gender specific with male specific messages relating to
      sexual roles and behaviours, physical sexual attributes and performance and
      sexuality related violence. Female specific messages were about female behaviours
      in a sexual relationship, financial stability and independence in relationships
      and physical sexual attributes. All themes were confirmed" through focus group
      discussions and additional information gleaned about how adolescents perceived
      the meanings and context of some expressions in the songs analysed. These themes
      informed the development of a questionnaire in both language and content.
      CONCLUSIONS: Gender specific issues about sexual relationships and performance,
      physical sexual attributes and sexual violence were common themes identified in
      Dancehall songs listed by adolescents. Focus group discussions confirmed
      adolescents' listenership to the themes and provided explanation of the perceived
      context and meaning of some messages.

PMID- 21866598
TI  - Postoperative nausea and vomiting in laparoscopic versus open cholecystectomy at
      two major hospitals in Jamaica.
AB  - Postoperative nausea and vomiting (PONV) is a distressing and potentially
      dangerous complication of general anaesthesia with volatile agents. The
      internationally reported average risk is 20 to 30%. It has been suggested that
      Jamaicans have a generally low risk of PONV and this is plausible since ethnic
      based differences in response to emetogenic stimuli have been identified. It has
      also been suggested that laparoscopy, by stretching and irritation of the
      peritoneum during gas insufflation, may be a risk factor for PONV but it has
      become increasingly difficult to test this hypothesis as fewer comparable open
      abdominal operations are being performed. This retrospective cohort study of PONV
      after laparoscopic versus open cholecystectomy was designed to answer these two
      questions. Data were collected on 356 cases performed at two major hospitals in
      Jamaica. The risk of PONV after laparoscopic and open cholecystectomy was 28.7%
      and 28.6% respectively. As these are at the upper end of the internationally
      reported average range, the impression that PONV risk is generally low in
      Jamaicans is not supported The finding that 81.4% of cases of PONV occurred only
      after discharge from the recovery room may explain the misconception. There was
      no significant difference between the risk of PONV after laparoscopic versus open
      cholecystectomy and the effect of laparoscopy remained insignificant after risk
      adjustment in a generalized linear regression model. Laparoscopy is not a major
      risk factor for PONV in this study.

PMID- 21866599
TI  - A review of granular cell tumours at the University Hospital of the West Indies:
      1965-2006.
AB  - OBJECTIVE: Granular cell tumours are uncommon lesions that occur in a wide
      variety of sites. They are usually benign, but as they are infrequently diagnosed
      preoperatively, they may be confused clinically with malignant lesions. The
      objective of this study was to assess the relative frequency and the
      clinicopathologic characteristics of granular cell tumours identified at the
      University Hospital of the West Indies (UHWI) over a 41-year period. METHODS: The
      archives of surgical pathology reports in the Department of Pathology at the UHWI
      from 1965 to 2006 were searched for all cases of granular cell tumour. From these
      records, a number of demographic and other data were recorded and analyzed.
      RESULTS: One hundred and thirty cases of granular cell tumours were found in 122
      patients. Of these, 99patients were female and 23 male, providing a male:female
      ratio of l to 4.3. The ages ranged from 5 days to 82 years with a mean age
      (excluding the 2 youngest cases) of 34.4 years. Lesions ranged in size from 0.2
      cm to 10 cm in greatest dimension, the average size being 1.85 cm and were found
      in a diverse array of anatomic locations, the most common being the vulva, breast
      and tongue. The correct clinical diagnosis was proffered preoperatively in only
      one case. In contrast, a malignant diagnosis was suggested in 19 cases.
      CONCLUSIONS: Compared with other studies, there was a notable difference in the
      distribution of granular cell tumours in this series. In particular lesions of
      the tongue accounted for fewer than expected, while lesions of the breast and
      vulva were considerably increased. The well-recognized female predominance was
      also substantially higher than in other studies.

PMID- 21866600
TI  - Distribution of nosocomial organisms and their resistance patterns in the
      intensive care unit of the University Hospital of the West Indies, Kingston,
      Jamaica.
AB  - OBJECTIVES: To determine the distribution and antibiotic susceptibility patterns
      of nosocomial pathogens in the Intensive Care Unit (ICU) at the University
      Hospital of the West Indies (UHWI). METHODS: A retrospective review of the
      laboratory records of all ICU patients from 2002-2004 was done. All organisms
      isolated from blood, urine, sputum, wound swabs and CVP tips were recorded.
      Sensitivity reports for organisms isolated in 2004 were also obtained. Results
      were analysed according to source of isolates and type of infection. RESULTS:
      Gram-negative organisms account for the majority oflCU isolates and show
      resistance to multiple antibiotics. The common Gram negative pathogens in the ICU
      are Pseudomonas aeruginosa, Acinetobacter spp and Stenotrophomonas maltophilia
      while the common Gram positive nosocomial organisms are Group D Streptococcus and
      coagulase negative Staphylococcus. CONCLUSION: The organisms isolated in the ICU
      at the UHWI are similar to those isolated in many ICUs all over the world.
      Surveillance data are necessary to monitor nosocomial pathogens and their
      resistance patterns to guide empirical antibiotic therapy.

PMID- 21866601
TI  - An assessment of clinical predictors of intracranial head injury identified by
      computed tomography scan.
AB  - A prospective study was done during a six-month period on 104 consecutive
      patients who were seen at the Accident and Emergency (A&E) Department of the UHWI
      and referred for CT scans of the head within 24 hours of sustaining head
      injuries. There were 74 (71.1%) males and 30 (28.8%) females. The mean age for
      females was 40.6 years and 32.4 years for males. Patients were clinically
      assessed for the presence or absence of vomiting, amnesia, loss of consciousness,
      bleeding of ear, nose and throat (ENT) and Glasgow Coma score (GCS). Negative
      predictive values were calculated for each parameter individually as well as the
      combination of all five. The absence of vomiting, amnesia, "loss of
      consciousness" (LOC) or ENT bleed had negative predictive values of 68%, 73%, 76%
      and 61.6% respectively. An assessment of Glasgow Coma Scale (GCS) of 15 had a
      77.5% negative predictive value. When the history was indeterminate, the negative
      predictive values were 19%, 25%, 60% and 18% respectively for vomiting, amnesia,
      LOC and ENT bleed. When all four clinical indicators were absent in the history
      and examination and the GCS score 15, the negative predictive value for
      intracranial injury was 89.4%. In summary, the clinical indicators reviewed,
      alone or in combination, cannot exclude the presence of intracranial injury.

PMID- 21866602
TI  - Pulmonary hypertension: a review of the aetiology, pathophysiology and
      management.
AB  - Pulmonary hypertension (PH) is defined as a systolic pulmonary artery pressure
      (PAP) above 30 mmHg and a mean PAP above 25 mmHg. Pulmonary hypertensive diseases
      (PHDs) encompass a myriad of conditions that cause pulmonary hypertension (PH),
      hence the Evian Classification was developed for the categorization of the
      various causes. Pulmonary hypertensive diseases are complex conditions that are
      difficult to treat and in the case of primary pulmonary hypertension, there is no
      known cure. Dyspnoea on exertion is the main symptom. This usually worsens as the
      disease progresses and can lead to syncope as a result of right ventricular
      failure. Prostacyclin has been the mainstay of treatment for decades, but several
      new drugs and alternate methods of treatment are currently available.

PMID- 21866603
TI  - Factors influencing the virulence of Candida spp.
AB  - BACKGROUND: Diseases produced for Candida species (spp) are called candidiasis
      and this includes settling, superficial infection, deep tissue invasion and
      haematogenic dissemination (eyes, the skin, the kidneys and the brain). The
      species that more usually cause candidiasis are C. albicans, C. tropicalis and C.
      glabrata. These species usually are found in the normal microbial populations of
      the mucosae and can be pathogenic due the vulnerability of the host. OBJECTIVE:
      The objective of this paper is to review the factors that influence infection by
      Candida spp in order to empower health-workers in the management of such
      infections. METHODS: Data were retrieved from the bibliographical data banks of
      SCIELO, HIGHWIRE, PUBMED, LILACS and SCIRUS. CONCLUSIONS: Knowledge about factors
      such as environment, exoenzymes, preferred infection sites and other factors that
      are essential for combating Candida infection and the risks associated with
      infection, will enhance efficient management.

PMID- 21866604
TI  - Outcome evaluation of patients requiring tracheostomy in an intensive care unit
      in Trinidad.
AB  - OBJECTIVE: To evaluate the outcome of patients who have undergone a tracheostomy
      in a multidisciplinary intensive care unit (ICU) and to determine the difference
      between an early and late tracheostomy. DESIGN AND METHODS: All patients who had
      tracheostomy in the ICU of The Eric Williams Medical Sciences Complex, Trinidad
      and Tobago, over a five-year period were retrospectively analysed. Data recorded
      included demographics, admission diagnoses, Glasgow Coma Score, Acute Physiology
      and Chronic Health Evaluation II score, Paediatric Index of Mortality II score,
      indication for endotracheal intubation and tracheostomy and the day it was
      performed, ICU and hospital length of stay and observed mortality. Predicted
      mortality was calculated. A comparison was made of patients who had tracheostomy
      before and after ten days following ICU admission. Validation of the prognostic
      models was done by Receiver Operating Curve (ROC) analysis. RESULTS: One thousand
      six-hundred and fourteen patients were admitted to ICU during the study period;
      51 patients (3%) underwent tracheostomy, of which 48 were studied. The overall
      mortality was 19.1% and 40.6% in tracheostomised patients. Patients who had
      tracheostomy within ten days had a significantly lesser predicted mortality and
      shorter ICU length of stay than those who had it after ten days (p = 0.01). The
      observed mortality was also significantly less in early-tracheostomised patients
      (p < 0.02). CONCLUSIONS: Tracheostomy should ideally be done within ten days
      following ICU admission when there is a clear need and indication for the
      procedure. Further delay may contribute adversely to the ICU morbidity and
      mortality.

PMID- 21866605
TI  - Risk and protective factors in the development of post-traumatic stress disorder
      symptoms among a cohort of students in two tertiary institutions post Hurricane
      Ivan.
AB  - OBJECTIVE: This study seeks to identify factors associated with post-traumatic
      stress disorder (PTSD) following Hurricane Ivan among a cohort of tertiary-level
      students in Jamaica. METHODS: A 22-item, self-administered questionnaire was
      administered to a non-random sample. Using parametric and non-parametric
      analyses, the relationship between PTSD symptoms and several variables was
      examined. RESULTS: Feeling anxious, worried or fearful and/or experiencing loss
      and injury during the hurricane were significant (p < 0.01) predictors for PTSD
      symptoms. CONCLUSIONS: Factors predicting the development of PTSD symptoms were
      feeling anxious, worried or fearful during the hurricane and experiencing loss of
      property and/or death or injury of a family member during the hurricane.

PMID- 21866606
TI  - Further insight into the bovine serum albumin assay (the in vitro anti
      inflammatory assay).
AB  - The present article reports on the comparative cost of using the Bovine Serum
      Albumin as an assay for detecting natural products with anti-inflammatory
      activities relative to the use of animals. This is an addendum to the West Indian
      Medical Journal article; 2008; 57(4); 327-31.

PMID- 21866607
TI  - Leiomyosarcoma of the kidney.
AB  - The case of a 42-year-old woman with leiomyosarcoma of the kidney, a very rare
      renal lesion, is presented. Leiomyosarcomas are the most common of the primary
      renal sarcomas which account for less than 1% of renal tumours in adults.

PMID- 21866608
TI  - Association between acute myeloblastic leukaemia and sarcoidosis.

PMID- 21866609
TI  - Use of a combined sliding and rotation flap to close a central forehead defect.

PMID- 21866610
TI  - The urgent need for addition suicide prevention measures among men in the United
      States of America.

PMID- 21866617
TI  - Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal
      barrier breakdown and bacterial translocation in rats.
AB  - BACKGROUND: Chemotherapy causes breakdown of the intestinal barrier, which may
      lead to bacterial translocation. Paclitaxel, an anti-tubulin agent, has many side
      effects; however, its effect on the intestinal barrier is unknown. Previous
      studies show that granulocyte colony-stimulating factor (G-CSF) plays an
      important role in modulating intestinal barrier function, but these studies are
      not conclusive. Here, we investigated the effects of paclitaxel on the intestinal
      barrier, and whether G-CSF could prevent paclitaxel-induced bacterial
      translocation. METHODS: Twenty-four male Sprague-Dawley rats were divided into
      three groups: control group, paclitaxel group and paclitaxel + G-CSF group.
      Intestinal permeability was measured by the urinary excretion rates of lactulose
      and mannitol administered by gavage. The mesenteric lymph nodes, spleen and liver
      were aseptically harvested for bacterial culture.Endotoxin levels and white blood
      cell (WBC) counts were measured and bacterial quantification performed using
      relative real-time PCR. Jejunum samples were also obtained for histological
      observation. Intestinal apoptosis was evaluated using a fragmented DNA assay and
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate(dUTP)
      biotin nick end-labeling staining. One-way analysis of variance and Fisher's
      exact test were used to compare differences between groups. RESULTS: Paclitaxel
      induced apoptosis in 12.5% of jejunum villus cells, which was reduced to 3.8% by
      G-CSF treatment.Apoptosis in the control group was 0.6%. Paclitaxel treatment
      also resulted in villus atrophy, increased intestinal permeability and a
      reduction in the WBC count. G-CSF treatment resulted in increased villus height
      and returned WBC counts to normal levels. No bacterial translocation was detected
      in the control group, whereas 6/8, 8/8, and 8/8 rats in the paclitaxel group were
      culture-positive in the liver, spleen and mesenteric lymph nodes, respectively.
      Bacterial translocation was partially inhibited by G-CSF. CONCLUSIONS: Paclitaxel
      disrupts the intestinal barrier, resulting in bacterial translocation. G-CSF
      treatment protects the intestinal barrier, prevents bacterial translocation, and
      attenuates paclitaxel-induced intestinal side-effects.

PMID- 21866618
TI  - [Abstracts of the 99th Annual Meeting of the Japanese Urological Association.
      April 21-24, 2011. Nagoya, Japan].

PMID- 21866619
TI  - [Abstracts of the 53rd Annual Meeting of the Japanese Society of Child Neurology.
      May 26-28, 2011. Yokohama, Japan].

PMID- 21866620
TI  - Bio-identical hormones.

PMID- 21866622
TI  - General surgery--a vision for the future.

PMID- 21866621
TI  - Mixed signals: trends in Americans' access to medical care, 2007-2010.
AB  - Likely reflecting the severe economic downturn and subsequent decline in demand
      for health care, the number and proportion of Americans reporting going without
      or delaying needed medical care declined modestly between 2007 and 2010,
      according to findings from the Center for Studying Health System Change's (HSC)
      nationally representative 2010 Health Tracking Household Survey. Despite
      increases in the number of uninsured, slightly more than one in six Americans--52
      million people--reported not getting or delaying needed medical care in 2010,
      down from one in five--58.6 million people--in 2007. The decline was driven
      primarily by fewer access problems for insured people, likely reflecting
      recession-related decreases in the demand for medical care. Nevertheless, the
      access gap between insured and uninsured people widened in 2010 compared to 2007,
      especially for lower-income people and those with health problems. Among people
      reporting problems getting medical care, the cost of care was an even bigger
      concern than in previous years. Fewer people encountered health system-related
      barriers, such as getting timely appointments with doctors, possibly reflecting
      freed-up health system capacity because of lower demand.

PMID- 21866623
TI  - [The effect of RhoA and proteasome inhibitor MG132 on angiogenesis in tumors].
AB  - OBJECTIVE: To investigate the effect of RhoA to VEGF, HIF-1alpha and MVD
      (microvascular density) and the effect of MG132 to RhoA. METHODS: The
      constitutively-active mutant vectors of RhoA (pCEFL-GST-V14RhoA) were transfected
      into gastric cancer cell line MKN-45 by Lipofectamine 2000, single clones were
      selected by G418 and identified with western blot. The content of VEGF in the
      conditioned media was detected by ELISA. Constitutively-active RhoA nude mice
      models were established and treated with MG132. The effect of RhoA and MG132 on
      expression of HIF-1alpha, VEGF and CD31 were detected by immunohistochemistry.
      RESULTS: Cell line of stable-transfected constitutively-active RhoA was
      established and constitutively-active RhoA could stimulate secretion of VEGF but
      MG132 inhibited that. Constitutively-active RhoA could obviously induce growth of
      tumor (P < 0.05), but MG132 inhibited it (P < 0.05). Constitutively-active RhoA
      could promote protein of HIF-1alpha, VEGF and CD31 but MG132 inhibited the
      function of RhoA (P < 0.05). CONCLUSION: Our studies indicates that MG132 could
      affect angiogenesis of tumors through inhibition the regulating function of RhoA
      on HIF-1alpha, VEGF and CD31.

PMID- 21866624
TI  - [The affect of Si-Rac1b on the malignant biological behaviors of colorectal
      cancer cell].
AB  - OBJECTIVE: To observe the affect of Small interfering RNA Rac1b (Si-Rac1b) on the
      malignant biological behaviors of colorectal cancer cell including the
      proliferation, migration, invasion and apoptosis of the cells. METHODS: Mediated
      by lipofectamine 2000, Si-Rac1b was transfected into colorectal cancer cell line
      SW1116 (with overexpression of Rac1b). The expression of Rac1b was detected by
      Western blotting and RT-PCR. The CCK-8 assay was used to analyze the cell
      proliferation, the Wound-healing assay and invasion assay were respectively
      applied to analyze the cell migration and invasion, and the Hoechst 33258 was
      used to evaluate the apoptotic index. RESULTS: Si-Rac1b can knock down the Rac1b
      but not Rac1 both in the level of mRNA and protein. In addition, Si-Rac1b could
      singnificantly facilitate the cell proliferation, migration, invasion and control
      the cell apoptosis. CONCLUSION: Si-Rac1b could partically reverse the malignant
      phenotypes of colorectal cancer cell.

PMID- 21866625
TI  - [RNA interference targeting focal adhesion kinase inhibited the growth of human
      hepatocellular carcinoma sk-hep-1].
AB  - OBJECTIVE: To test the impact of silencing focal adhesion kinase (FAK) gene on
      human hepatocellular carcinoma cell line sk-hep-1 using RNA interference (RNAi)
      in vitro, and its therapeutic effect on human hepatocellular carcinoma xenograft
      in vivo. METHODS: The plasmids generating short hairpin RNA that target FAK gene
      were transfected into sk-hep-1 cell line through Fugene HD. The impact was
      analyzed using flow cytometry, RT-PCR and western bolt. Human hepatocellular
      carcinoma xenograft in nude mice was established and treated with injection of
      the plasmids that packaged by cationic liposome into the tail veins the mice. The
      volumes and weights of the tumors were measured. The tumor tissues were analysed
      with FAK, CD31 and PCNA immunohistochemistry and TUNEL. RESULTS: The RNAi
      targeting FAK significantly down regulated the expression of FAK in mRNA and the
      level of protein (P < 0.001), and increased the cell apoptosis in vitro. The mice
      treated with pshFAK had slower tumor growth, resulting in smaller tumor size and
      lower tumor weight (P < 0.001) comparing to the controls. Decrease in FAK protein
      expression, tumor angiogenesis and proliferation, and increase in tumor apoptosis
      were found in the mice treated with pshFAK compared to the controls (P < 0.001).
      CONCLUSION: The shRNA targeting FAK suppresses the FAK expression of human
      hepatocellular carcinoma cells sk-hep-1, inhibits tumor growth, and promotes cell
      apoptosis in vitro and in vivo. FAK could become a candidate target for liver
      cancer treatment.

PMID- 21866626
TI  - [Inhibitory effect of recombinant HMGN2 protein on human hepatitis B viral].
AB  - OBJECTIVE: To construct a prokaryotic expression recombinant for the expression
      of HMGN2 and to evaluate its antiviral activity against human hepatitis virus.
      METHODS: The extracellular region cDNA of HMGN2 was isolated and amplified by RT
      PCR, and introduced to the prokaryotic expression vector pGEX-4T-1. HMGN2 protein
      was expressed under IPTG induction and purified by GST protein purification
      system, then identified by SDS-PAGE and Western blot. The cytotoxicity of fusion
      HMGN2 to HBV-transfected HepG2. 2.15 cell was evaluated with MTT assay. Different
      concentration of fusion HMGN2 was applied on the HepG2. 2.15 cell and the cell
      culture supernatants were harvested after 3 and 6 days treatment. The HBsAg and
      HBeAg in the supernatants were detected by ELISA and the HBV DNA was detected by
      RT-PCR. RESULTS: In the range of tested 1-100 microg/mL of HMGN2, no cytotoxicity
      to HepG2. 2.15 cells was detected by MTT assay. When incubated with HMGN2 at 15
      microg/mL for 72 h or 144 h, there was a significant reduction in HBeAg and HBsAg
      expression as well as the HBV DNA copies. CONCLUSION: pGEX-4T-1/HMGN2 vector was
      success constructed, and the recombinant HMGN2 protein could inhibit HBV
      expression and replication in vitro remarkably.

PMID- 21866627
TI  - [The effect of small GTPase Cdc42 on the multidrug resistance of oxaliplatin
      resistant colon cancer cell lines].
AB  - OBJECTIVE: To determine the effect of cell division cycle42 (Cdc42) on the
      multidrug resistance of oxaliplatin-resistant human colon cancer cells. METHODS:
      The protein expression levels of Cdc42 in oxaliplatin-resistant colon cancer
      cells and parental cells were examined with Western blot. pDEST26-His-Cdc42 was
      transfected by lipofectamine 2000 into SW480 and Colo320 cells with low
      expression of Cdc42. Cdc42 siRNA was transfected by lipofectamine 2000 into
      SW480/L-OHP and Colo320/L-OHP cells with high expression of Cdc42. The expression
      of Cdc42 in these cell lines were examined by Western blot and RT-PCR 48 hours
      after transfection. The sensitivity of colon cancer cells to antitumor drugs was
      evaluated using CCK-8 assay. The concentration of each drug that caused a 50%
      reduction in the numbers of cells (IC50) was calculated. The expression of P-gp,
      MRP1 in SW480/Cdc42 and Colo320/ Cdc42 cells were examined with Western blot.
      RESULTS: Cdc42 was over-expressed in the SW480/L-OHP and Colo320/L-OHP cell
      lines. Over-expression of Cdc42 significantly enhanced the resistance of colon
      cancer cells to multiple antitumor drugs and up-regulated the expression of P-gp
      and MRP1. CONCLUSION: Cdc42 enhances the resistance of colon cancer cells to
      several antitumor drugs. It might become a potential target for reversing
      multidrug resistance of colon cancer.

PMID- 21866628
TI  - [The antagonistic effect of PI3K-gamma inhibitor AS605240 on cardiac hypertrophy
      and cardiac fibrosis induced by isoproterenol in rats].
AB  - OBJECTIVE: To investigate the therapeutic effect of PI3Kgamma inhibitor AS605240
      on cardiac hypertrophy and cardiac fibrosis induced by Isoproterenol in rats.
      METHODS: Wistar rats were randomly divided into three groups (n = 10), control
      group, ISO group (vehicle group) and AS605240 group. The rats in control group
      without any treatment. The rats in ISO and AS605240 group were given ISO 10 mg/kg
      for 3 days and 5 mg/kg for another 11 days by subcutaneous injection to prepare
      the animal model of cardiac fibrosis. Rats in AS605240 group were given AS605240
      50 mg/(kg x d) by intraperitoneal injection continuously for 14 days. The vehicle
      group received the intraperitoneal injection of an equal volume of 0.5%
      carboxymethylcellulose. Twenty-four hours after the last treatment, rats were
      sacrificed. Heart, body weight, cardiac function and the CVF were measured.
      RESULTS: Compared with the control group, the HW/BW of ISO group was increased
      significantly (P < 0.05) with a increased collagen inter cardiac muscle cells (P
      < 0. 05). Compared with ISO group, histological examination of the heart showed
      that AS605240 significantly relieved the rat cardiac fibrosis and reduced
      heart/body weight ratios in experimental cardiac fibrosis (P < 0.05). CONCLUSION:
      AS605240 may be an effective antagonist for cardiac hypertrophy and cardiac
      fibrosis.

PMID- 21866630
TI  - [Preparation of a hyaluronic acid modified bovine serum albumin nanoparticle and
      its anti-tumor effect].
AB  - OBJECTIVE: To prepare hyaluronic acid modified bovine serum albumin nanoparticle,
      investigate the modification extent, the drug entrapment property and its anti
      tumor effect. METHODS: Bovine serum albumin nanoparticles were prepared by
      desolvation method, then use hyaluronic acid to modify the surface of bovine
      serum albumin nanoparticle. The decrement of reactive amino groups on the surface
      of bovine serum albumin nanoparticles was applied to evaluate the modification
      extent of hyaluronic acid. Single factor was used to study the effects of several
      influencing factors in preparation on the modification extent of hyaluronic acid
      modified bovine serum albumin nanoparticles. The influence of pH on drug
      entrapment ratio as well as the drug entrapment property were studied. The
      inhibition rate of nanoparticle on HepG2 was evaluated with MTT asasay. RESULTS:
      The prepared hyaluronic acid modified bovine serum albumin nanoparticle had a
      average particle size of 396 nm, and Zeta potential of - 19.7 mV, the deceased
      ratio of surface reactive amino groups was 34.28%; hyaluronic acid modified
      mitoxantrone bovine serum albumin nanoparticles had a property of drug load ratio
      11.13%, drug entrapment ratio 94.64% and 398 nm average particle size, Zeta
      potential - 17.9 mV, with a distinguished delayed drug release effect. A higher
      inhibition rate was observed for hyaluronic acid modified bovine serum albumin
      nanoparticle than that of mitoxantrone solution (P < 0.05). CONCLUSION: The
      preparation technique is stable which could be used to prepare hyaluronic acid
      modified bovine serum albumin nanoparticle, and the prepared nanoparticle has a
      higer anti-tumor effect than that of mitoxantrone solution.

PMID- 21866629
TI  - [Improved therapeutic effectiveness by combining recombinant human RhoB with low
      dose cisplatin in human lung cancer in nude mice].
AB  - OBJECTIVE: To determine the antitumor effects of the recombinant human RhoB with
      low-dose cisplatin in lung carcinoma models. METHODS: The pVITRO2-RhoB
      recombinant was constructed and transfected into A549 cells. Its expression and
      the inhibition effect to the A549 cells were observed models. A549 lung carcinoma
      mice were treated with either RhoB or cisplatin or both agents together. And the
      change of tumor size, the survive time of mice, the apoptosis of tumor were also
      observed. RESULTS: The pVITRO2-RhoB recombinant was constructed successfully.
      This recombinant could inhibit the growth and promote the apoptosis of A594 in
      vitro. Mice treated with RhoB or low-dose cisplatin treatment individually
      resulted in tumor inhibition to a certain extent. Mice treated with combination
      of RhoB and low-dose cisplatin resulted in synergistic antitumor activity with
      more effective tumor inhibition (P < 0.05) and longer survival (P < 0.05). TUNEL
      analysis of tumors exhibited that RhoB in combination with cisplatin led to the
      increased rate of apoptosis (P < 0.05). CONCLUSION: Our data demonstrated that
      RhoB could increase the sensitivity of lung carcinoma to cisplatin, resulting in
      enhanced anti-tumor activity. These results suggest that combination with
      recombinant human RhoB with chemotherapy drugs may be an effective approach in
      the treatment of lung carcinoma.

PMID- 21866631
TI  - [Construction and analysis of one kind of chitosan-coated BMP-2 nanoparticles as
      genetic carrier].
AB  - OBJECTIVE: To construct an excellent kind of chitosan-coated BMP-2 nanoparticles
      as genetic carrier. METHODS: Chitosan-coated BMP-2 nanoparticles as genetic
      carrier, including C-B50 group, C-B100 group and C-B200 group, were constructed
      through re-coacervation and gene recombination methods. This carrier was studied
      by using morphological observation, enveloping test, anti- DNase I digested test
      and MTT assay. RESULTS: One kind of excellent chitosan-coated BMP-2 nanoparticles
      as genetic carrier was constructed. Particle diameter was about (90 +/- 20) nm.
      Enveloping ratio of C-B50 group, C-B100 group and C-B200 group was 76.31% +
      1.58%, 84.49% + 1.81% and 81.69% + 1.77%, respectively. Genetic carrier could
      prevent objective gene from DNase I digestion. The growth inhibiting ratio to
      bone marrow stem cells was increased as the increase of genetic carrier dose and
      contact time (P < 0.05), but maximal dose of carrier had no obvious toxic effect
      on cells growth in vitro. CONCLUSION: The constructed chitosan-coated BMP-2
      nanoparticle material was a promising genetic carrier in bone tissue engineering.

PMID- 21866632
TI  - [Relationship between activation of mannan-binding lectin complement and NF
      kappaB in diabetic nephropathy].
AB  - OBJECTIVE: To study the activation of mannose-binding lectin (MBL) complement in
      STZ-induced diabetic nephropathy (DN) rats and its relationship with NF-kappaB.
      METHODS: Sprague-Dawley (SD) rats were randomly divided into two groups: normal
      control and diabetic nephropathy. Diabetes was induced by intraperitoneal
      injection of STZ. Five rats were sacrificed at the end of week 1, 2, 4, 8
      respectively. Blood glucose, 24 h urine, 24 h urinary albumin, serum creatinine
      (Scr), body mass and kidney mass were examined at the same time points
      respectively. Creatinine clearance and renal hypertrophy index were calculated.
      The renal expression of MBL, membrane attack complex (MAC) and NF-kappaB were
      determined by immunohistochemistry. RESULT: MBL, MAC and NF-kappaB expression
      were significantly increased in glomerulus of diabetic nephropathy rats compared
      to the controls. The expression of MBL was positively correlated with NF-kappaB
      expression. CONCLUSION: The activation of mannose-binding lectin complement
      participates in the onset and development of DN.

PMID- 21866633
TI  - [Anti-inflammatory and analgesic effects of saponins from D. zingiberensis C. H.
      Wright and diosgenin derivative on mice].
AB  - OBJECTIVE: To determine the potential anti-inflammatory and analgesic activities
      of saponins from D. zingiberensis C. H. Wright and diosgenin derivative on xylene
      induced acute ear edema in mice. METHODS: 3beta-2-acetoxy-benzoyl-diosgenin ester
      (ABDE) was synthesized by acylation of aspirin through two-step of reaction. The
      analgesic activities of ABDE and saponins were investigated through acetic acid
      induced writhing response of the mice. The anti-inflammatory effects of saponins
      and ABDE were observed on the xylene-induced swelling ears of the mice. RESULTS:
      The structure of ABDE was confirmed by 1H-NMR and ESI-MS. ABDE had significantly
      higher anti-inflammatory and analgesic activities than the comparison drug. The
      saponins demonstrated 7.92% and 14.51% anti-inflammatory activities at the dose
      of 126 mg/kg and 252 mg/kg, respectively, and 15.38% and 26.15% analgesic
      activities at the dose of 126 mg/kg and 252 mg/kg, respectively. CONCLUSION: The
      saponins of D. zingiberensis C. H. Wright possess acute nonspecific anti
      inflammatory and analgesic effects. The anti-inflammatory and analgesic effects
      of ABDE are equivalent to aspirin.

PMID- 21866634
TI  - [The effect of nimesulide on learning and memory function after serve traumatic
      brain injury in rats].
AB  - OBJECTIVE: To investigate the effect of a cyclooxygenase-2 inhibitor nimesulide
      on learning and memory function of rats after traumatic brain injury (TBI).
      METHODS: The model of severe closed TBI was established according to the method
      created by Marmarou. Adult Wistar rats (n = 480) were randomly divided into TBI
      group, nimesulide treatment group, sham operation group, normal controls, and
      each of them was subdivided into posttraumatic 1, 3, 6, 12, 24, 48, 72, 96, 168,
      and 336 h groups. The nimesulide treatment group after injury was treated with
      nimesulide [6 mg/(kg x d)] in peritoneum. The TBI group, the sham operation
      group, and the control group were treated with normal saline. All rats were
      killed at each time point, COX-2 protein expression was evaluated with Western
      blot and immunohistochemistry. Another 24 rats were randomly divided into TBI
      group, nimesulide treatment group, sham operation group, and normal group. The
      cognitive dysfunction was evaluated using the Morris water maze (MWM). RESULTS:
      The increased expression of protein COX-2 in brain after TBI was observed. A
      significantly decreased peak of COX-2 protein expression was observed in
      nimesulide treated group when compare with that of TBI (P < 0.05). An significant
      shorter latency of MWM tests at 9,10 days after nimesulide treatment was also
      observed (P < 0.01). CONCLUSION: Nimesulide may play a protective role on
      learning and memory function on severe traumatic brain injury of rats.

PMID- 21866635
TI  - [Effect of ginsenoside Rg1 on angiogenesis after neonatal hypoxia ischemia brain
      damage in rats].
AB  - OBJECTIVE: To investigate effects of ginsenoside Rg1 on angiogenesis in neonatal
      rats with hypoxia ischemia brain damage (HIBD), and explore the possible
      mechanism. METHODS: Fifty-four of 10-day-old SD rats were randomly divided into
      sham-operation group (n = 6), hypoxia-ischemia brain damage group (n = 24) and
      ginsenoside Rg1 treatment group (n = 24). SD rats in HIBD group and Rg1 group
      were treated by separation and ligation of right common carotid artery (CCA) and
      subsequently exposed to hypoxia for 2.5 hours, and those in sham group were
      treated by only separation of right CCA, without ligation or exposure to hypoxia.
      Intraperitoneal injection of 0.1 mL normal saline (NS) containing 40 mg/kg Rg1
      was performed immediately after operation in Rg1 group, and such process was
      repeated every 24 h for 3 days. Intraperitoneal injection of 0.1 mL pure NS was
      performed in both HIBD group and sham group, in the same way as that of in Rg1
      group. General state of SD rats after operation was monitored, 4, 8, 24 and 72
      hours after HIBD, animals were executed and the right side of brain tissue was
      separated for further process. Protein expression of both hypoxia inducible
      factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were
      detected by both Western blot and immunohistochemistry. Immunohistochemistry for
      von willebrand factor (vwf) was used to labeling micro vessels. RESULTS: All rats
      survived to the end of the study and neurological dysfunction was observed in
      both HIBD group and Rgl group, but not in sham group. Expression of HIF-1alpha
      protein in HIBD group was increased at 4, 8, 24 and 72 h, compared to that in
      sham group (P < 0.05). Expression of HIF-1alpha protein in Rg1 group was
      increased compared to that in HIBD group at the same time points (P < 0.05).
      Expression of VEGF protein in HIBD group was increased at 4, 8, and 24 h,
      compared to that in sham group (P < 0.05). Expression of VEGF protein in Rg1
      group was increased at 24 and 72 h compared to that in HIBD group at the same
      time point (P < 0.05). Number of vwf-positive cells at 24 and 72 h in HIBD group
      was increased compared to that in sham group (P < 0.05), and number of vwf
      positive cells at 72 h in Rg1 group was increased compared to that in HIBD group
      at the same time point (P < 0.05). CONCLUSION: Rg1 could facilitate angiogenesis
      after HIBD in Neonatal rats by strengthening and stabilizing HIF-1alpha/VEGF
      signaling pathway.

PMID- 21866636
TI  - [The study on the beclin1 expression and change in diabetic rats].
AB  - OBJECTIVE: To study the expression of beclin1 in renal tissue of diabetic rats,
      and its role in diabetic nephropathy (DN). METHODS: Diabetic rat model was
      produced by intraperitoneal injection of streptozotocin (50 mg/kg), it was
      considered to be diabetic nephropathy that 72 h blood glucose after modeling was
      higher than 16 mmol/L. The positive urine protein was detected by paper method at
      the end of 1 week. 24 h urine albumin excretion (ALb) and urinary albumin and
      urinary creatinine ratio (ACR) were examined by immunoturbidimetry, Beclin1
      expression was also studied by immunohistochemistry with envision method. The
      electron microscopy was used to detect the form of autophagic vesicles and
      lysosome. RESULTS: (1) Compared with control group, the 24-hour urinary albumin
      excretion rate and ACR in diabetic rats were significantly higher. (2) The
      electron microscopy showed there were autophagic vesicles in renal tissue in both
      groups; (3) Immunohistochemistry showed beclin1 expression in normal rat kidney
      cells partly, while no expression in glomeruli. The expression of beclin1 in DN
      renal tissue was stronger than that in normal rats (P < 0.05). CONCLUSION:
      beclin1 may be involved in the pathogenesis of diabetic nephropathy with the
      mechanism related to the process of programmed cell death.

PMID- 21866637
TI  - [Detection and genotyping of rotavirus in diarrhea infant feces in Chengdu].
AB  - OBJECTIVE: To study the genotype of rotavirus and the genetic variations of the
      major neutralization antigen VP4 of group A rotavirus in fecal samples from
      infants with diarrhea in Chengdu, Sichuan province, China. METHODS: The fecal
      specimens were collected from infant patients with diarrhea in the spring of 2010
      at West China Second University Hospital. Reverse transcription polymerase chain
      reaction (RT-PCR) was performed to identify rotavirus G serotypes and P
      genotypes. VP4 gene fragments of the virus were amplified from two strains drawn
      randomly from the prevailing genotype and cloned into a T-A clone vector to
      generate the recombinants for sequencing. RESULTS: A group rotaviruses were
      detected in 13 of 75 specimens (17.3%). Serotype G1 was the predominant type
      (7/13) and two were serotype G3, four strains' serotypes were unidentified.
      Analysis of P gene demonstrated that genotype P [8] was the predominant type
      (6/13), whereas only two P[4] genotype were detected and genotypes for two
      strains were not determined. G1P [8] was the predominant type of G/P dominance
      combination (5/13). Sequencing results of the VP4 gene for the analyzed two
      strains implied that they were genotype P[8] with a 97% homology in sequence.
      Compared with the standard strain, homologies were also more than 90%.
      CONCLUSION: Rotavirus is one of the major etiological agents of viral diarrhea
      among infants in Chengdu. G1 was the dominant type G in Chengdu. G1P[8] was the
      predominant type of G/P dominance combination.

PMID- 21866638
TI  - [Influence of ALA-PDT on fibroblast cells from hypertrophic scars].
AB  - OBJECTIVE: To determine the effect of ALA-PDT on fibroblast cells from
      hypertrophic scars in vitro, and to identify proper dosage of photosensitizer and
      energy level of laser light. METHODS: Fibroblast cells from hypertrophic scars
      were cultured in vitro. ALA (5-aminolevulnilic acid) was added into the culture
      fluid with different concentrations. Then the cultured cells were exposed to He
      Ne laser light (PDT) with different energy levels. The cell inhibition rate was
      measured with CCK-8 method. The expression of PCNA in fibroblast cells was
      detected after cultured with ALA-PDT, which was selected according to the proper
      dosage of ALA and laser light from the result of CCK-8. RESULTS: No obvious
      inhibition effect was detected with laser light or photosensitizer alone on
      fibroblast cells from hypertrophic scars. The inhibition effect appeared when ALA
      and PDT applied simultaneously, and the inhibition rate increased with the dosage
      of photosensitizer and the energy level of laser light. Maximal inhibition effect
      reached with 20 J/cm2 laser light exposure and 0.5 mmol/L of ALA, the expression
      of PCNA of ALA-PDT group is lower than control group in this condition (30.33 +/-
      2.08 vs. 78.33 +/- 3.79, P < 0.05). CONCLUSION: The inhibition effect of ALA-PDT
      on fibroblast cells from hypertrophic scars increases with the dosage of
      photosensitizer and the energy level of He-Ne laser light. The proper dosage of
      ALA is 0.5 mmol/L along with 20 J/cm2 laser light exposure.

PMID- 21866639
TI  - [Effects of exercise and nilestriol on bone size and bone mass in ovariectomized
      rats].
AB  - OBJECTIVE: To investigate the influence of nilestriol (CCE3) and exercise on bone
      size and bone mass in ovariectomized (OVX) rats. METHODS: Forty eight (48) female
      Sprague-Dawley (SD) rats were divided randomly into six groups: (1) Normal
      control group, (2) Sham OVX group, (3) OVX group, (4) OVX + CCE3 group, (5)) OVX
      + exercise group, (6) OVX + CCE3 + exercise group. CCE (0.5 mg/kg per week) was
      given to the rats in OVX + CCE3 group and OVX + CCE3 + exercise group from the
      2nd day after the operation for 11 weeks. Exercise training was loaded to the
      rats in exercise groups from the 7th day after operation, each rat was subjected
      to running on 0 dig angle runway with the speed of 16 m per minute, 45 minutes
      per day, 5 days per week for 10 weeks. RESULTS: The bone diameter, bone volume,
      bone wet weight, bone dry weight, bone ashes weight in the OVX group were lower
      than those in the sham OVX group (P < 0.01). All of these measurements were
      increased in OVX + CCE3 group and OVX + exercise group when compared with the OVX
      group, but were still lower than those in sham OVX group (P < 0.01). Exercise
      enhances the effect of CCE3 (P < 0.01). CONCLUSION: Exercise enhances the effects
      of CCE3 on the improvement of both bone size and quantity in OVX rats.

PMID- 21866640
TI  - [The effects of prolonged sevoflurane anesthesia on renal function in liver
      fibrosis rabbits].
AB  - OBJECTIVE: To determine the effects of prolonged sevoflurane anesthesia on renal
      function in liver fibrosis rabbits. METHODS: Fifty male new zealand rabbits were
      randomly divided into two groups: fibrosis group (n = 40) and normal control
      group (Group N, n = 10). In the fibrosis group, experimental liver fibrosis was
      induced by subcutaneous injection of carbon tetrachloride (CCl4 soluted in oil
      with the concentration of 500 mL/L). Twelve weeks later, 24 rabbits survived in
      fibrosis group were randomly allocated to control group (Group F, n = 12) or
      treating with sevoflurane (Group S, n = 12). Both group S and group N received
      1.0 minimum alveolar concentration (MAC) sevoflurane for 8 h with a fresh gas
      flow rate of 1 L/min. Group F was just given fluid infusion. After 8 h of 1.0 MAC
      anesthesia, sevoflurane was discontinued. Blood samples were collected before
      (T0) and 8 h (T8), 24 h (T24), 72 h (T72), and 120 h (T120) after anesthesia. The
      renal function was assessed by blood urea nitrogen (BUN) and creatinine (Cr). The
      serum inorganic fluoride was measured by ion-selective electrode. The
      pathological consequences of the livers were obtained after 5 days or when the
      rabbits died. RESULTS: All the rabbits in group S and group F developed liver
      fibrosis. The hepatic function was significantly abnormal in group S and group F.
      Aminotransferase (AST), glutamic-pyruvic transaminase (ALT), lactate
      dehydrogenase (LDH) and total bile acid (TBA) were significantly higher in the
      fibrosis group (group S and group F) than those in group N. Alkaline phosphatase
      (ALP) in the fibrosis group was lower than that in group N. There were no
      significant differences of hepatic function between group S and group F. There
      were no significant differences in renal function and serum inorganic fluoride
      before and after anesthesia among the three groups. In group N and S, BUN and
      serum inorganic fluoride increased slightly at T8, and serum Cr was highest at
      T72. All of them returned to basic line at T120. In group F, BUN increased
      slightly at T8, and serum Cr was highest at T72. Serum inorganic fluoride was
      highest at T120. BUN and serum Cr returned to basic line at T120. CONCLUSION:
      Prolonged sevoflurane anesthesia has no significant influences on renal function
      in normal and liver fibrosis rabbits.

PMID- 21866641
TI  - [Pancreatic fat fraction in healthy men measured with MRI chemical shift
      imaging].
AB  - OBJECTIVE: To detect the range of pancreatic fat fraction in healthy men, and the
      distribution of fat in pancreas. METHODS: A calibration curve was established by
      standard fat-water mixture model. Then, 83 healthy men were selected randomly.
      The participants were divided into three groups by age: group A 20-30 years (29
      cases), group B 31-40 years (27 cases), group C 41-50 years (27 cases). The fat
      content in pancreas of the participants were quantified with double-echo chemical
      shift gradient-echo MR. RESULTS: A perfect correlation between the MRI
      measurements and the true value of fat-water mixture was found (r = 0.996,
      P<0.01). There was no significant difference in the fat content of 3 different
      pancreatic regions (P>0.05). The 95% confidence interval of fat fraction ranged
      from 1.25%-4.83%, 1.58%-4.35%, 1.41%-4.75%, and 1.87%-4.19% in pancreatic head,
      body,nail and whole pancreas, respectively. No significant differences were found
      between the age groups (P>0.05). CONCLUSION: Chemical-shift MR imaging is a
      reliable and safe noninvasive technique for the detection and quantification of
      fat. It can be useful in quantifying the fat fraction of pancreas. The fat
      content in healthy men of 20-50 years does not vary with age and in different
      pancreatic regions.

PMID- 21866642
TI  - [Characterize the differences between anisometropic amblyopes and normal people
      when discriminating different pictures under various degrees of Gauss noises].
AB  - OBJECTIVE: To observe the differences between anisometropic amblyopes and normal
      people when all of them were asked to discriminate those topological and non
      topological pictures embedded in Gauss noises. METHODS: Stimulus pictures (noise
      variance were 0.04, 0.08, 0.12 respectively) were run using Matlab software, the
      error ratios of identification of amblyopia groups and control groups were
      recorded. RESULTS: The P-values of anisometropic amblyopes were 0.06 (closure
      pictures) and 0.088 (disclosure pictures) under the different experimental
      lasting time. No matter whenever the experimental lasting time and whatever the
      characteristics of the pictures, the error ratios of identification of amblyopia
      groups were higher than that of control groups, except for closure pictures at 5
      s. CONCLUSION: The capabilities of amblyopes when discriminate the different
      pictures were lower than that of normal groups. We found that different outcomes
      of amblyopia groups were caused by their own perception defect.

PMID- 21866643
TI  - [Risk factors of obstructive sleep apnea hypopnea syndrome and its treatment in
      female patients].
AB  - OBJECTIVE: To identify risk factors of obstructive sleep apnea hypopnea syndrome
      (OSAHS) in female patients, and assess its treatment and health-related quality
      of life (HRQoL) of the patients. METHODS: One hundred and ninety three female
      patients undergoing polysomnography whith sleep breath disorders were recruited
      and divided into non-OSAHS group and OSAHS group. Age, body mass index (BMI), and
      prevalence of menopause and hypertension were compared between the two groups.
      The associations of those variables with apnea hypopnea index (AHI) and lowest
      pulse oxygen saturation (LSpO2) were analysed. The treatment of OSAHS and its
      impact on HRQoL assessed by the Calgary quality of life index (SAQLI) were
      evaluated. RESULTS: The OSAHS group had greater mean age, BMI, and prevalence of
      menopause and hypertension than the non-OSAHS group (P<0.05). Those variables
      were significantly correlated with AHI and LSpO2 (P<0.05). Weight control and
      positional therapy were the most common treatment for sleep breath disorders.
      Weight loss and continuous positive airway pressure improved the Epworth sleep
      scale (ESS) of the patients with OSAHS significantly (P<0.05). But positional
      therapy made no difference (P>0.05). The ESS of the 32.5% of patients who did not
      undergo any treatment was worsened during the same period of time (P<0.05). No
      differences were found in the scores of the four domains of SAQLI between the two
      groups (P>0.05). The stepwise multiple regression analysis identified Pittsburgh
      sleep quality index (PSQI), ESS and AHI as independent predictors for the total
      score of SAQLI (P<0.05). CONCLUSION: Older age, greater BMI, menopause and
      hypertension are risk factors of OSAHS in female patients. OSAHS was not well
      managed in female patients. PSQI, ESS and AHI can be used as predictors for
      HRQoL.

PMID- 21866644
TI  - [Association of occupational stress with quality of working life].
AB  - OBJECTIVE: To assess occupational stress and quality of working life (QWL) and
      their association in workers with different jobs. METHODS: The Occupational
      Stress Inventory Revised Edition (OSI-R) and Quality of Working Life Scale (QWL7
      32) were administered to 194 workers in the Liaohe Oilfield. The association
      between occupational stress and quality of working life was analysed by
      controlling job types and other confounding variables. RESULTS: Office workers
      had significantly lower scores in occupational role questionnaire (ORQ) and
      personal strain questionnaire (PSQ) and higher scores in personal resources
      questionnaire (PRQ) and QWL than physical laborers (P<0.05). The PSQ scores were
      positively correlated with the ORQ scores and negatively correlated with the PRQ
      scores. The QWL scores were negatively correlated with the ORQ and PSQ scores,
      and positively correlated with the PRQ scores (P<0.001). The QWL scores changed
      with job types. The QWL scores declined with the increase of stress levels
      (P<0.01). ORQ, role boundary (RB), role insufficiency (RI), physical environment
      (PE), PSQ, vocational strain (VS), interpersonal strain (IS) and PRQ had a
      significant impact on quality of working life (P<0.01). CONCLUSION: Occupational
      stress is associated with quality of working life. Quality of working life can be
      improved through control of occupational stress.

PMID- 21866645
TI  - [Application of wavelet neural networks model to forecast incidence of syphilis].
AB  - OBJECTIVE: To apply Wavelet Neural Networks (WNN) model to forecast incidence of
      Syphilis. METHODS: Back Propagation Neural Network (BPNN) and WNN were developed
      based on the monthly incidence of Syphilis in Sichuan province from 2004 to 2008.
      The accuracy of forecast was compared between the two models. RESULTS: In the
      training approximation, the mean absolute error (MAE), rooted mean square error
      (RMSE) and mean absolute percentage error (MAPE) were 0.0719, 0.0862 and 11.52%
      respectively for WNN, and 0.0892, 0.1183 and 14.87% respectively for BPNN. The
      three indexes for generalization of models were 0.0497, 0.0513 and 4.60% for WNN,
      and 0.0816, 0.1119 and 7.25% for BPNN. CONCLUSION: WNN is a better model for
      short-term forecasting of Syphilis.

PMID- 21866646
TI  - [Application of Rogerson spatial pattern surveillance in monitoring infectious
      diseases: parameter setting and choice of scales of analysis].
AB  - OBJECTIVE: To set up appropriate parameters and scales of analysis for monitoring
      infectious diseases using Rogerson spatial pattern surveillance method. METHODS:
      Hepatitis data in Henan provinces from 2006 to 2009 were tested using Rogerson
      spatial patterns surveillance method. RESULTS: When the parameters were set with
      n0 = 12, K= 0.5, H = 7.17, r = 25 and analyzed at city level, 26 alarms were
      triggered. When the parameters were set with n0 = 4, K = 0.5, H = 8.26, r = 15
      and analyzed at county level, 115 alarms were triggered. CONCLUSION: K and a need
      to be set first, followed by n0 and r with adaptation to the anticipated numbers
      of alarm. Then, the parameters of ARL0, ARL1, and H can be calculated. For the
      surveillance of hepatitis A, county level analysis is more reasonable than city
      level.

PMID- 21866647
TI  - [The diagnostic value of digital subtraction angiography in detecting small
      intestinal bleeding].
AB  - OBJECTIVE: To determine the diagnostic value of digital subtraction angiography
      (DSA) in detecting small intestinal bleeding. METHODS: DSA was performed in 39
      patients with suspected small intestinal bleeding. The sensitivity, specificity
      and accuracy of DSA were evaluated in the 25 patients who accepted surgical
      treatment. RESULTS: Among the 39 patients, 33 came out with positive in DSA.
      Eight patients were given interventional embolization successfully. The
      sensitivity, specificity and accuracy of DSA in detecting small intestinal
      bleeding were 91.7%, 100% and 92% respectively. The pathological results
      confirmed 77.3% of etiological diagnosis by DSA. CONCLUSION: DSA is an effective
      method for detecting small intestinal hemorrhage. The accurate diagnosis can
      guide the intervention with embolization.

PMID- 21866648
TI  - [Distinguishing benign and malignant lesions with time-signal intensity curve of
      dynamic contrast-enhanced breast MRI scanning].
AB  - OBJECTIVE: To determine the diagnostic value of time-signal intensity curve (TIC)
      in distinguishing breast malignant tumors from benign lesions. METHODS: Forty
      four patients with 50 breast lesions were recruited in the study, including 24
      pathologically confirmed benign lesions and 26 malignant tumors. All patients
      received dynamic contrast-enhanced breast MRI scanning a week before surgery. The
      time-signal intensity curves in the regions of interest (ROI) and eight items of
      TIC including shape, T peak, E peak, Slope(i), E1, E2, W peak-7, and W peak-9
      were compared between benign lesions and malignant tumors. The receive operating
      characteristic curves (ROC) were depicted for those indicators with significant
      statistical differences. RESULTS: Six items of TIC including shape, T peak,
      Slope(i), E1, E2, and W peak-9 were significantly different (P<0.05) between
      malignant tumors and benign lesions. The sensitivities of shape, T peak,
      Slope(i), E1, E2, and W peak-9 for diagnosing breast malignant tumors were 92.3%,
      95.83%, 80.77%, 61.53%, 69.23%, and 69.23% respectively. Their specificities were
      87.5%, 92.3%, 95.8%, 87.5%, 79.17%, and 79.17% respectively. TIC curve shape, T
      peak and Slope(i) were better than E1, E2 and W peak-9 in diagnosing breast
      malignant lesions (P<0.05). CONCLUSION: Benign and malignant breast tumors can be
      differentiated according to TIC. TIC curve shape, T peak and Slope(i) are better
      than E1, E2 and W peak-9 in distinguishing malignant breast tumors from benign
      lesions.

PMID- 21866649
TI  - [Monitoring urine metabolic profiles of rat inflammation model with capillary
      electrophoresis].
AB  - OBJECTIVE: To determine the comprehensive metabolic profiling of inflammation
      with capillary zone electrophoresis (CZE) in rat urine. METHODS: CZE-based
      metabolomics method was used to acquire urine metabolom data, with Computer Aided
      Similarity Evaluation System aligning peaks and analyzing urine profiling.
      Principle component analysis (PCA) was performed to compare and classify the
      phenotypes of the urine CZE spectra. RESULTS: The PCA revealed different
      phenotypes of metabolites between rats with and without inflammation, which were
      independent from gender, individual diversity, day-night diversity and diurnal
      variation. CONCLUSION: CZE-based metabolomics method could be used as a potential
      tool for urinary profiling for disease diagnosis and drug studies.

PMID- 21866650
TI  - [Determination of biapenem in human plasma by high performance liquid
      chromatography].
AB  - OBJECTIVE: To establish a method to determine biapenem in human plasma with high
      performance liquid chromatography. METHODS: Chromatographic separation was
      performed on a YMC-C18 column (150 mmX 4. 6 mm, 5 microm) eluted with a mobile
      phase comprising 98 : 2 (V = V) of sodium acetate (0.1 mol/L, adjust with acetic
      acid to pH 4.5) and acetonitrile with a flow rate of 1.0 mL/min. The detection
      wavelength was set at 300 nm. Temperature was controlled at 35 degrees C. The
      plasma samples were precipitated with acetonitrile. The supernatant was vortexed
      with dichloromethane and 0.03 mL of the aqueous layer was injected for analysis.
      RESULTS: The method was valid to detect biapenem in a range of 0.0625 mg/L to 80
      mg/L (correlation coefficient 0.999). The pretreatment recovery of biapenem
      ranged from 96.11% to 98.76%. The methodological recovery of biapenem ranged from
      99.14% to 109.69%. The inter-day RSD ranged from 0.92% to 2.79%. The intra-day
      RSD ranged from 2.46% to 4.08%. Less than 7% change of results was observed after
      the sample was stored in room temperature for 5 h, frozen and defrozen 3 times,
      stored at -30 degrees C for 28 d, stayed in autosampler for 24 h, and injected
      twice. CONCLUSION: The method is sensitive, accurate and easy to perform, which
      offers a satisfactory tool for the determination and pharmacokinetic study of
      biapenem.

PMID- 21866651
TI  - [The prospective of integrative medical treatment of oncology in the next ten
      years].

PMID- 21866652
TI  - [Assessment of therapeutic efficacy on treating advanced non-small cell lung
      cancer in the aged by Chinese medicine adopting the international questionnaire
      of quality of life].
AB  - OBJECTIVE: To assess the therapeutic efficacy of treating advanced non-small cell
      lung cancer (NSCLC) in the aged by Chinese medicine (CM) adopting the
      international questionnaire of quality of life (QOL). METHODS: 91 aged patients
      with advanced NSCLC were randomly assigned to three groups. There were 31 in the
      CM group (Group I), 30 in the chemotherapy group (Group II), and 30 in the CM and
      chemotherapy combination group (Group III). Oral administration of CM decoction
      and intravenous dripping of Chinese patent medicine was given to those in Group
      I. Patients in Group II received chemotherapeutic protocol alone. Patients in
      Group III received chemotherapeutic protocol while orally taking CM decoction.
      Twenty-eight days were taken as one therapeutic course, and two courses in total.
      Assessment was performed using European Organization for Research and Treatment
      of Lung Cancer Quality of Life Questionnaire LC-43 (EORTC QLQ-LC43) before
      treatment, the 10th day of the second therapeutic course, and the 28th day of the
      second therapeutic course, respectively. RESULTS: After two therapeutic courses
      of treatment, compared with Group II, better effects were obtained in Group I and
      Group III in the aspects of the physical function, roles function, emotional
      functions, social functions, general health state, and short breath, cough,
      fatigue, insomnia, poor appetite, and constipation (P<0.05, P<0.01). CONCLUSIONS:
      CM therapy could relieve the clinical symptoms of aged patients with advanced
      NSCLC and improve their QOL.

PMID- 21866653
TI  - [Study on qi deficiency syndrome distribution and quality of life in patients
      with advanced non-small cell lung cancer].
AB  - OBJECTIVE: To study the qi deficiency syndrome distribution and quality of life
      (QOL) of patients with advanced non-small cell lung cancer (NSCLC). METHODS: A
      questionnaire survey was conducted in 120 patients with advanced NSCLC using the
      QOL scale "Functional Assessment of Cancer Therapy" (FACT-L) (Version 4.0).
      Meanwhile, syndrome typing was performed. On the basis of results of syndrome
      typing, patients of different syndrome types were grouped and compared, thus
      studying the distribution of advanced NSCLC patients of qi deficiency syndrome
      and qi deficiency syndrome correlated QOL features. RESULTS: Qi deficiency, blood
      stasis, yin deficiency, phlegm and dampness dominated in syndrome types of the
      120 patients with advanced NSCLC. Of syndrome types accounting for larger ratios
      in 112 patients, pure qi deficiency syndrome accounted for 30.36% (34 cases), qi
      deficiency and blood stasis syndrome for 18. 75% (21 cases), both qi and yin
      deficiency syndrome for 10. 71% (12 cases). There was no correlation between the
      appearance of qi deficiency syndrome and patients' age, sex, pathological typing
      (adenocarcinoma/squamous carcinoma), or the disease duration. NSCLC patients in
      phase IV were mostly complicated with qi deficiency syndrome (P<0.05). Scores of
      physical states, emotional states, functional states, and total scores in the
      FACT-L scale were lower in those complicated with qi deficiency syndrome (89
      cases) than in those without complicated qi deficiency syndrome (31 cases),
      showing statistical difference (P<0.01, P<0.05). The scores of the lung cancer
      specific module (additional concerns) in the FACT-L scale showed statistical
      difference, sequenced as qi deficiency and blood stasis syndrome > pure qi
      deficiency syndrome > both qi and yin deficiency syndrome (P<0.05). CONCLUSIONS:
      Qi deficiency syndrome is the main syndrome of advanced NSCLC. The QOL of
      advanced NSCLC patients complicated with qi deficiency syndrome was poorer than
      those without complicated qi deficiency syndrome. Besides, along with the
      aggravation of qi deficiency syndrome, the QOL decreased somewhat. It suggested
      that symptomatic treatment of qi deficiency syndrome could improve advanced NSCLC
      patients' QOL.

PMID- 21866654
TI  - [Clinical study on improving decreased gastrointestinal motility of post
      operative esophageal cancer patients by unblocking the interior and purgation
      method].
AB  - OBJECTIVE: To observe the clinical effect of unblocking the interior and
      purgation method on improving decreased gastrointestinal motility of post
      operative esophageal cancer patients, and to study its mechanisms. METHODS: 60
      patients with post-operative esophageal cancer were randomly assigned to two
      groups, the treatment group and the control group, 30 in each group. Routine
      therapies were given to the two groups. Chinese drugs with unblocking the
      interior and purgation action was infused by enteral nutrition tube to patients
      in the treatment group, while normal saline was infused to those in the control
      group. The first flatus time, the first defecation time, the bowel tones recovery
      time after operation, and the total amount of the gastric juice draining between
      the first day and the third day after operation of all patients were recorded.
      Plasma motilin (MTL) and vasoactive intestinal peptide (VIP) contents were
      detected before operation and the fourth day after operation. RESULTS: The first
      flatus time, the first defecation time, the bowel tones recovery time after
      operation, and the total amount of the gastric juice draining were less in the
      treatment group than in the control group, showing statistical difference
      (P<0.05, P<0.01). The post-operative MTL contents were higher and VIP contents
      lower in the treatment group than in the control group, showing statistical
      difference (P<0.05, P<0.01). There was no significant difference in plasmal MTL
      and VIP contents of the treatment group between before and after treatment
      (P>0.05). But there was significant difference in plasmal MTL and VIP contents of
      the control group between before and after treatment (P<0.01). CONCLUSION:
      Unblocking the interior and purgation method could significantly promote the
      gastrointestinal motility recovery of post-operative esophageal cancer patients,
      showing good clinical effect.

PMID- 21866655
TI  - [Clinical study of combination of Chinese medicine and western medicine in
      treatment of 500 patients with hemophilia hemorrhage].
AB  - OBJECTIVE: To study the effect and safety of haemostatic apozem combined with
      haemostatic mixture on hemophilia hemorrhage. METHODS: Five hundred hemophilia
      patients were randomly recruited from Shaanxi Yida Hematology Institute from
      February 2005 to July 2010. Under the condition of using no blood products such
      as platelet cofactors VIII and IX, oral administration of haemostatic apozem
      combined with intravenous dripping of haemostatic mixture were given to 332
      hemorrhagic patients and 451 patients in need of surgery for hemorrhagic
      prevention. The treatment was lasted for three successive weeks. The hemostatic
      time, hemorrhage absorption (recovery) time, and their safety were observed.
      RESULTS: The hemostatic time for open bleeding and closed bleeding was (0.85 +/-
      0.83) h and (2.69 +/- 0.65) h respectively. The average hemostatic time was (2.00
      +/- 0.69) h. The recovery time for different portions was as follows
      respectively: intra-cranial hemorrhage (14.13 +/- 6.01) days; muscular hemorrhage
      (18.18 +/- 7.34) days; hematuria (8.25 +/- 4.69) days; arthrorrhagia(3.27 +/-
      1.31) days; ecchymoma (7.16 +/- 2.32) days; bleeding of oral and nasal cavities
      (4.26 +/- 1.35) days; intramedullary hemorrhage (19.15 +/- 1.36) days; hematoma
      ulceration (50.01 +/- 20.91) days. The hemorrhage recovery ratio was 99.10%
      (329/332). The success rate of preventing from surgery hemorrhage was 100%
      (451/451). No severe adverse reaction occurred during the therapeutic course.
      CONCLUSIONS: Haemostatic apozem combined with haemostatic mixture was effective
      and fast in preventing and treating hemophilia hemorrhage, with no complications
      or adverse reactions. It could be taken as the first choice for prevention and
      treatment of hemophilia hemorrhage.

PMID- 21866656
TI  - [Clinical study on treatment of endometriosis-related infertility patients by
      laparoscopic surgery in combination of quyu jiedu recipe].
AB  - OBJECTIVE: To study the clinical efficacy of the laparoscopic surgery in
      combination of Quyu Jiedu Recipe (QYJDR) on endometriosis (EMs)-related
      infertility patients. METHODS: 130 EMs-related infertility patients of blood
      stasis and toxin accumulation syndrome diagnosed and treated by laparoscopic
      surgery were randomly assigned to two groups, i.e., the test group (75 cases) and
      the control group (55 cases). All patients received routine progesterone
      treatment after laparoscopic surgery. QYJDR was given to patients in the test
      group after laparoscopic surgery, lasting for twelve months. The pregnancy rate
      within one year after laparoscopic surgery were compared between the two groups.
      The Chinese medicine syndrome integrals, serum endometrium antibody (EMAb) and
      cancer antigen 125 (CA125) levels were compared between before drug therapy and
      three months after drug therapy. RESULTS: The pregnancy rate within one year
      after laparoscopic surgery was higher in the test group than in the control group
      [61.33% (46/75) vs 45.45% (25/55)], showing significant difference (P<0.05). The
      Chinese medicine syndrome integral was (16.07 +/- 6.77) score and (7.25 +/- 3.27)
      score before and 3 months after drug therapy in the test group, while it was
      (15.92 +/- 7.51) score and (12.73 +/- 6.12) score in the control group. The
      Chinese medicine syndrome integral after drug therapy was lower than that before
      drug therapy in the same group. Besides, the integral difference between before
      and after drug therapy was higher in the test group than in the control group
      [(9.12 +/- 6.16) score vs (3.48 +/- 2.06) score)], showing statistical difference
      (P<0.05). After three-month drug therapy, the serum EMAb negative conversion rate
      was obviously higher in the test group than in the control group (44.44% vs
      15.62%), showing statistical difference (P<0.05). The serum CA125 level was
      (31.88 +/- 15.78) U/mL before drug therapy and (18.82 +/- 10.08) U/mL three
      months after drug therapy in the test group, while it was (30.63 +/- 19.28) U/mL
      and (18.05 +/- 11.20) U/mL respectively in the control group. It was lowered
      after drug therapy in the two groups with statistical difference (P<0.05). There
      was no statistical difference between the two groups after drug therapy (P>0.05).
      CONCLUSIONS: The laparoscopic surgery in combination of QYJDR could effectively
      improve clinical symptoms of EMs patients of blood stasis and toxin accumulation
      syndrome, promote negative conversion of EMAb, lower serum CA125 levels, and
      elevate the clinical pregnancy rate. QYJDR is an effective formula in treatment
      of EMs-related infertility.

PMID- 21866657
TI  - [Correlation between Chinese medicine syndrome types of polycystic ovary syndrome
      and ovulation induction effect].
AB  - OBJECTIVE: To study the correlation between Chinese medicine syndrome types of
      polycystic ovary syndrome (PCOS) and ovulation induction effect, and its clinical
      significance. METHODS: Eighty patients with clinically confirmed PCOS were
      syndrome differentiated as four types, i.e., Shen-yin deficiency syndrome (21
      cases), Shen-yang deficiency syndrome (18 cases), phlegm-dampness accumulation
      syndrome (19 cases), and Gan-stagnancy transformed heat syndrome (22 cases). They
      all took 100 mg clomiphene as the ovulation induction for 5 successive days.
      Results of ovulation in all patients were analyzed and compared. RESULTS:
      Ovulation induction and the conception rate were sequenced from high to low as
      follows: Shen-yang deficiency syndrome (66.7%, 22.2%), Gan-stagnancy transformed
      heat syndrome (59.1%, 18.2%), Shen-yin deficiency syndrome (28.6%, 9.5%), and
      phlegm-dampness accumulation syndrome (26.3%, 5.3%). Significant difference was
      shown in ovulation induction results when compared Shen-yang deficiency syndrome
      with Shen-yin deficiency syndrome and phlegm-dampness accumulation syndrome
      (P<0.05) as well as when compared Ganstagnancy transformed heat syndrome with
      Shen-yin deficiency syndrome and phlegm-dampness accumulation syndrome (P<0.05).
      Significant difference was shown in the conception rate between Shen-yang
      deficiency syndrome and phlegm-dampness accumulation syndrome (P<0.05).
      CONCLUSION: The effects of ovulation induction in patients of phlegm-dampness
      accumulation syndrome and of Shen-yin deficiency syndrome were poorer than those
      in patients of Shen-yang deficiency syndrome and Gan-stagnancy transformed heat
      syndrome, which indicated the reproduction endocrine abnormality or the
      metabolism abnormality degree of the former two syndrome types were more server
      than the latter two syndrome types.

PMID- 21866658
TI  - [Effect of danshen chuanxiongqin injection on the myocardial damage of unstable
      angina patients undergoing percutaneous coronary intervention].
AB  - OBJECTIVE: To observe the effect of Danshen Chuanxiongqin Injection (DCI) on the
      myocardial damage of unstable angina (UA) patients undergoing percutaneous
      coronary intervention (PCI). METHODS: 76 UA patients were randomly assigned to
      the test group (39 cases) and the control group (37 cases). Routine treatment of
      Western medicine and PCI were given to all patients. But 10 mL DCI was
      intravenously dripped to patients in the test group by adding in 250 mL normal
      saline three to five days before PCI, once daily, lasting for 7 to 10 days.
      Changes of platelet P-selectin positive expressions before and after medication,
      the thrombolysis in myocardial infarction (TIMI), myocardial perfusion (TMP)
      score, levels of creatine kinase-myocardial band (CK-MB) and troponin I (TnI)
      after PCI were observed in the two groups. RESULTS: After medication the P
      selectin positive expressions was lower in the test group than in the control
      group (2.45% +/- 1.42% vs 4.43% +/- 1.79%, P<0.05). After PCI the incidence of
      TMP 0/1, the levels of CK-MB and TnI were lower in the test group than in the
      control group at the same phase, showing statistical difference (P<0.05). No
      cardiac event occurred in the two groups during the hospital stay. CONCLUSION:
      Administration of DCI before PCI could effectively inhibit the activation of
      platelets, improve post-operative myocardial blood perfusion, and lower the
      incidence of the myocardial damage.

PMID- 21866659
TI  - [Clinical epidemiologic investigation on Chinese medicine syndrome laws in
      patients with chronic heart failure].
AB  - OBJECTIVE: To study the distribution laws of Chinese medicine syndromes in
      patients with chronic heart failure (CHF) by clinical epidemiologic
      investigation. METHODS: 512 CHF patients were studied, including 168 items of
      symptoms and 48 items of tongue and pulse pictures. A database of Chinese
      medicine syndromes was established, and 9 disease nature elements and 5 disease
      location elements were extracted. Frequency analysis was performed on all
      symptoms, tongue and pulse pictures. The variables with frequency constituent
      ratio less than 10.0% were deleted. Then the features of clinical epidemiology,
      syndrome patterns, syndrome elements, main symptoms, as well as tongue and pulse
      pictures were analyzed. RESULTS: (1) The disease nature elements of CHF covered
      qi deficiency, yin deficiency, and yang deficiency (categorized as the essential
      deficiency), as well as blood stasis, turbid phlegm, and the retained fluid
      (categorized to the superficiality excess). Among them, frequencies of qi
      deficiency and blood stasis (both more than 85.0%) were the highest. The disease
      location elements of CHF were ordered in frequency as Xin (97.9%), Pi (88.1%),
      followed by Shen (43.0%), Fei (30. 1%), and Gan (7.0%). (2) In the distribution
      of syndrome patterns in CHF patients, qi deficiency phlegm-stasis syndrome was
      the most (59.2%), followed by qi-yin deficiency with phlegm-stasis intermingle
      syndrome (20.3%), Xin-yang decline with phlegm-stasis obstruction syndrome
      (7.0%), and yang-deficiency with water overflowing syndrome (5.5%). (3) Patients
      with heart function grade II, III, and IV mainly manifested as qi-deficiency with
      phlegm-stasis syndrome. Besides, qi-yin deficiency with phlegm-stasis intermingle
      syndrome could be often seen in those with grade III. And Xin-yang decline with
      phlegm-stasis obstruction syndrome and yang-deficiency with water overflowing
      syndrome could often be seen in those with grade IV. CONCLUSIONS: The
      pathogenesis of CHF is essential deficiency and superficiality excess. The
      essentiality consists of qi deficiency, yin deficiency, and yang deficiency, and
      the superficiality consists of blood stasis, turbid phlegm, and retained fluid.
      The disease was located at the five zang-organs, mainly dominated at Xin and Pi,
      and associated with Fei, Shen, and Gan. Qi deficiency phlegm-stasis syndrome was
      dominated in Chinese medicine syndrome patterns. Along with the aggravation of
      CHF, Chinese medicine syndrome pattern shows certain development laws.

PMID- 21866660
TI  - [Correlation study between carotid atherosclerosis and hypertension].
AB  - OBJECTIVE: To study the correlation between carotid atherosclerosis (CAS) and
      hypertension. METHODS: Color Doppler ultrasonography data of CAS were observed in
      150 hypertension patients [as the hypertension group, including 70 patients in
      the phlegm-stasis syndrome (PSS) group and 80 in the non-PSS group] and 30 non
      hypertension patients (as the control group). The difference of the CAS
      occurrence was compared among the three groups. RESULTS: The incidence of CAS was
      higher in the PSS group and the non-PSS group than in the control group, showing
      statistical difference (P<0.01). Of them, it was higher in the PSS group than in
      the non-PSS group (P<0.05). Hard plaque dominated in the CAS plaque constitution
      in both the PSS group and the non-PSS group. Of them the soft plaque ratio was
      higher in the PSS group than in the non-PSS group, showing statistical difference
      (41.9% vs 11.4%, P<0.05). The CAS plaque distribution positions among the three
      groups (P>0.05). The inner diameters of the left and right common carotid artery,
      and the resistant indices of the left and right common carotid artery, the left
      internal carotid artery, and the left vertebral artery in the PSS group and the
      non-PSS group were higher than in the control group (P<0.05). CONCLUSIONS:
      Hypertension patients are often accompanied with CAS of various degrees.
      Especially the soft plaque ratio of the CAS plaque was higher in those of PSS,
      indicating the possibility of target organs damage such as cerebral infarction
      was higher.

PMID- 21866661
TI  - [Proteomics study on the essence of wind syndrome caused by gan-yang
      hyperactivity in Chinese medicine].
AB  - OBJECTIVE: To preliminarily study the essence of wind syndrome caused by Gan-yang
      hyperactivity (WSGH) in Chinese medicine at the protein expression level.
      METHODS: WSGH was strictly differentiated from wind stirring due to yin
      deficiency syndrome in patients with intracerebral hemorrhage (ICH) and those
      with cerebral infarction (CI); from Gan-yang hyperactivity syndrome in patients
      with cervical spondylosis (CS); from wind syndrome induced by blood deficiency in
      patients with Parkinson's disease (PD) according to Chinese medicine syndrome
      typing standard. Control studies were performed. Peripheral blood mononuclear
      cells (PBMCs) were isolated from all patients of the aforesaid syndromes and
      healthy subjects. The total proteins were extracted, two-dimensional gel
      electrophoresis (2-DE) conducted and analyzed by PDQuest software. The peptide
      mass fingerprint (PMF) was determined using matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The
      SwissProt database was inquired using Mascot reference system. Proteins of
      different and same expressions in PBMCs of patients suffering from the same
      disease of different syndromes, different diseases of the same syndrome, and
      syndromes of the same kind were compared. RESULTS: The 2-DE map of PBMCs' total
      proteins in the aforesaid syndrome groups and healthy subjects was established.
      Through comparison, analysis, and appraisement, there was 1 protein dot of the
      same expression and 22 protein dots of different expressions between ICH patients
      of WSGH and ICH patients of wind stirring due to yin deficiency syndrome. There
      were 6 protein dots of the same expression and 21 protein dots of different
      expressions between CI patients of WSGH and CI patients of wind stirring due to
      yin deficiency syndrome. There were 3 protein dots of the same expression and 12
      protein dots of different expressions between CS patients of WSGH and CS patients
      of Gan-yang hyperactivity syndrome. There was no protein dot of the same
      expression and 12 protein dots of different expressions between PD patients of
      WSGH and PD patients of wind syndrome induced by blood deficiency. There were 13
      protein dots of the same expression in different diseases of the same syndrome.
      There was 1 protein dot (Thioredoxin-dependent peroxide reductase, TPx) of the
      same expression in the four diseases of the same kind syndrome. CONCLUSIONS:
      Different connotations of the essence existed (having multiple different protein
      expressions) in patients with the same disease of different syndromes. Syndromes
      of the same kind share the same material bases (having the same protein
      expression). These suggested that Chinese medicine syndrome has its own material
      bases and essence findable.

PMID- 21866662
TI  - [Effect of SPPW on the invasive and metastatic capacities of human gastric cancer
      cells].
AB  - OBJECTIVE: To clarify the action and possible mechanisms of SPPW, a Chinese
      herbal preparation consisting of Herba Scutellariae Barbatae, Radix Astragalus,
      Radix Glycyrrhizae, etc., in suppressing the metastasis of human gastric cancer,
      by way of observing its effect on the invasive and metastatic capacities of
      gastric cancer cells. METHODS: In vitro serial sub-cultured human gastric cancer
      cell line SGC-7901 at the logarithmic growth phase were randomly divided into 5
      groups, i.e. the negative control group, the 4 treatment groups intervened
      respectively with SPPW at three different doses (high, middle, and low), and 5
      FU. The adhesion capacities of gastric cancer cells to matrigel were detected by
      MTT assay 48 h after intervention. The invasive and migratory capacities of
      gastric cancer cells were determined by Transwell assay. The mRNA and protein
      expressions of metalloproteinase-9 (MMP-9) and vascular endothelial growth factor
      (VEGF) in gastric cancer cells were detected by Western blot and Real-time
      polymerase chain reaction (RT-PCR) respectively. RESULTS: Compared with the
      negative control group, the adhesive, invasive and migratory capacities of
      gastric cancer cells were all significantly inhibited in the four treatment
      groups (P<0.05, P<0.01). In addition, the protein and mRNA expressions of MMP-9
      and VEGF were down-regulated (P<0.01). Significant dose-dependent relation
      existed in the three SPPW treatment groups (P<0.01). Compared with the 5-FU
      treatment group, the high dose SPPW treatment group showed significant difference
      in inhibiting the adhesive and metastatic capacities of gastric cancer cells,
      lowering VEGF protein expression, and mRNA expressions of MMP-9 and VEGF
      (P<0.01). CONCLUSIONS: SPPW could lower the adhesion of gastric cancer cells to
      matrigel, and lower the invasion and migration of gastric cancer cells.
      Meanwhile, it could down-regulate the mRNA and protein expressions of MMP-9 and
      VEGF, which may possibly be one of its mechanisms for influencing the invasion
      and metastasis of gastric cancer cells.

PMID- 21866663
TI  - [Jianpi jiedu recipe inhibited Helicobacter pylori-induced the expression of
      cyclooxygenase-2 via p38MAPK/ATF-2 signal transduction pathway in human gastric
      cancer cells].
AB  - OBJECTIVE: To study the effect of Jianpi Jiedu Recipe (JJR) on the expression of
      cyclooxygenase (COX-2) in Helicobacter pylori (Hp) infected gastric cancer cell
      line MKN 45, and its regulatory mechanism of p38MAPK signal transduction.
      METHODS: The expressions of COX-2 mRNA and protein in human gastric cancer cell
      line MKN 45 infected by Hp type strain NCTC 11637 and the regulatory effect of
      JJR containing serum were detected using Real-time fluorescent quantitative
      polymerase chain reaction (RFQ-PCR) and Western blot. The effects of Hp on COX-2
      mRNA and protein expressions in human gastric cancer cell line MKN 45 were
      observed using blocking p38MAPK signal transduction pathway by p38MAPK specific
      inhibitor SB203580. The effects of JJR on Hp-infection activated p38MAPK signal
      transduction pathway and its downstream activating transcription factor 2 (ATF-2)
      were observed. RESULTS: COX-2 mRNA and protein expressions were obviously higher
      after human gastric cancer cell line MKN 45 were infected by Hp (P<0.01). After
      blocking p38MAPK signal transduction pathway, COX-2 mRNA and protein expressions
      in Hp-induced MKN 45 cell line were obviously down-regulated (P<0.01). JJR
      containing serum down-regulated Hp-induced COX-2 mRNA and protein expressions in
      MKN 45 cell line in a dose dependent manner. Besides, it could inhibit the
      activation of Hp-induced p38MAPK signal pathway. It also showed obvious
      inhibition on the activity of its downstream transcription factor ATF-2.
      CONCLUSIONS: Hp infection induced COX-2 expressions of gastric cancer cells via
      p38MAPK signal transduction pathway. JJR inhibited Hp-induced the expression of
      COX-2 through regulating p38MAPK/ATF-2 signal transduction pathway, which may be
      one of its mechanisms in prevention and treatment of Hp-induced gastric cancer.

PMID- 21866664
TI  - [Effect of shuanghuangbu on the adhesion growth and proliferation of human
      periodontal ligament cells on the zein stent].
AB  - OBJECTIVE: To study the effect of Shuanghuangbu on the adhesion growth and
      proliferation of human periodontal ligament cells (HPDLCs) on the zein scaffold,
      and to study the feasibility of Shuanghuangbu zein used in the periodontal tissue
      engineering as a compound scaffold material. METHODS: HPDLCs were cultured in
      vitro using the explants adherent method. Shuanghuangbu Decoction was prepared
      using water extraction and alcohol precipitation method. Zein scaffold was
      prepared using solvent casting/corpuscle leaching method, which was dispensed
      into Shuanghuangbu culture fluid at the concentration of 50, 100, 150, 200, 500,
      1000 microg/mL, respectively. Shuanghuangbu of different concentrations groups,
      the zein scaffold leaching liquid group, and the cell control group were also set
      up. The effect of each group on the proliferation of HPDLCs was detected by MTT.
      According to results of MTT, the best concentration of Shuanghuangbu (100
      microg/mL) was selected as the experiment group. Ten percent FBS of DMEM culture
      fluid was taken as the control group. The effect of Shuanghuangbu on the
      morphology of HPDLCs on the zein scaffold was observed using inverted phase
      contrast microscope and scanning electron microscope. RESULTS: Compared with the
      zein scaffold leaching liquid group and the cell control group, the proliferation
      of HPDLCs could be promoted by different concentrations of Shuanghuangbu culture
      fluid, with the most obvious effect shown by Shuanghuangbu at 100 microg/mL
      (P<0.01). There was no obvious difference between the zein scaffold leaching
      liquid group and the cell control group (P>0.05), but their cell proliferation
      rates were positive values. The morphological results demonstrated that HPDLCs
      successfully grew on the zein scaffold. The number of HPDLCs under the action of
      Shuanghuangbu was more and the morphous was better. CONCLUSIONS: Shuanghuangbu
      could promote the adhesion growth and proliferation of HPDLCs on the zein
      scaffold. Shuang- huangbu zein was feasible to be used in the periodontal tissue
      engineering as a compound scaffold materia.

PMID- 21866665
TI  - [Effect of shugan jianpi bushen recipe on splenic T lymphocytes and virus load in
      hepatitis B virus transgenic mice].
AB  - OBJECTIVE: To observe the effect of Shugan Jianpi Bushen Recipe (SJBR) on the
      splenic T lymphocytes and virus load in the hepatitis B virus (HBV) transgenic
      (Tg) mice, and to study its antiviral efficacy and mechanisms of action. METHODS:
      Sixty male BALB/C mice of SPF grade were included. Ten non-HBV Tg male mice were
      included as the normal control group. Fifty HBV Tg mice were randomly divided
      into five groups, i. e., the model group, the adefovir (ADV) group, the low dose
      SJBR group, the middle dose SJBR group, and the high dose SJBR group, ten in
      each. 10, 20, and 40 g/kg SJBR crude drug was respectively given by gastro-gavage
      to mice in the low dose SJBR group, the middle dose SJBR group, and the high dose
      SJBR group. ADV 50 mg/kg body weight was given by gastrogavage to mice in the ADV
      group. Equal volume of sterilized iso-osmia was given to mice in the normal group
      and the model group. The medication was performed once daily, totally for 21
      successive days. The serum HBV DNA titers of HBV Tg mice were detected using Real
      time fluorescent PCR one day before administration (T0), ten days after
      administration (T1), 21 days after administration (T2), and three days after
      withdrawal (T3), respectively; the serum hepatitis B surface antigen (HBsAg) of
      HBV Tg mice on T3 was detected by ELISA. The splenic T lymphocyte percent of all
      mice was detected by flow cytometry. RESULTS: Serum HBsAg at TO was positive in
      the high-, middle-, low-dose SJBR, and ADV groups. The HBsAg negative rate at T3
      was lower in the high dose SJBR group than in the ADV group, showing statistical
      difference (P<0.01). Compared with TO of the same group, the serum HBV DNA titers
      could be continually decreased by high dose SJBR, showing statistical difference
      (P<0.01). The serum HBV DNA titers also gradually decreased in the ADV group
      (P<0.01), but it somewhat increased at T3. The CD3+ cell percent could be
      elevated by high-, middle-, low-dose SJBR, and ADV groups (P<0.05, P<0.01). The
      CD8+ T cell percent could also be obviously lowered by high-, middle-, and low
      dose SJBR (P<0.01). Compared with the middle-, low-dose SJBR, and ADV groups, the
      CD4+ T cell percent and CD4+/CD8+ increased as well as CD8+ decreased in the high
      dose SJBR group, showing statistical difference (P<0.01). The CD3+ T cell percent
      was significantly positively correlated to the decrement of HBV DNA titers
      between the pre-treatment and post-treatment in the middle dose SJBR group
      (r=0.654, P<0.05). The percents of CD4+, CD8+ T cells and CD4+/CD8+ were
      significantly positively correlated to the decrement of HBV DNA titers between
      the pre-treatment and post-treatment in the high dose SJBR group (r=0.53, r=0.79,
      r =0.80, P<0.01). CONCLUSIONS: SJBR were capable of inhibiting the HBV DNA
      duplication of HBV Tg mice. One of its anti-HBV mechanisms possibly be improving
      the the abnormality of T lymphocyte subsets and the immune function.

PMID- 21866666
TI  - [Mechanism of huoxiang zhengqi extract for regulating the intestinal motility in
      rat model of diarrhea-predominant irritable bowel syndrome].
AB  - OBJECTIVE: To study the regulatory effect of Huoxiang Zhengqi Extract (HZE) on
      the intestinal mobility in rat model of diarrhea-predominant irritable bowel
      syndrome (D-IBS). METHODS: Eighty experimental rats were randomly divided into
      two parts, forty in each. Rats in one part were used in the carbon powder
      experiment, while the rest rats were used in the gastrointestinal transit test.
      Rats in each part were divided into five groups, i.e., the blank control group,
      the model group, and the high, moderate, and low HZE treated groups, eight in
      each. Normal rats consisted of the blank control group. Except for the blank
      control group, D-IBS model was established by gastrogavage of senna at the dose
      of 0.2 g/mL at 25 degrees C with 2-h restraint stress of extremities for six
      successive days. After modeling, high (804 mg/kg), moderate (536 mg/kg), and low
      (268 mg/kg) dose HZE was respectively administered to rats of the three
      corresponding groups. Effect of HZE on the small intestine propulsion rate and
      serum levels of nitric oxide (NO), 5-hydroxytryptamine (5-HT) as well as
      chromaffin cells in colonic epithelium (EC) were detected by carbon powder
      experiment, gastrointestinal transit test, nitrate reductase method, ELISA, and
      immunohistochemistry, respectively. RESULTS: Compared with the model group, HZE
      could lower the small intestine propulsion rate of D-IBS model rats, attenuate
      the colon transition, improve serum NO level, lower 5-HT level, and lessen the
      amount of EC. CONCLUSION: HZE showed regulatory effect on the intestinal function
      of D-IBS rats.

PMID- 21866667
TI  - [Correlation study of rhubarb and expression changes of antimicrobial peptides in
      the small intestine of mice].
AB  - OBJECTIVE: To study the correlation between rhubarb and expressions of
      antimicrobial peptides (AP) in the small intestine of mice by observing the
      effect of rhubarb on it. METHODS: Thirty healthy ICR mice were randomly divided
      into the test group and the control group, fifteen in each. Ten percent rhubarb
      decoction and equal volume of normal saline solution was respectively given to
      mice of the two groups by gastrogavage. Mice were sacrificed 24 h later. The
      small intestines from the ligament of Treitz to the ileocecal junction were
      removed by ventrotomy. The lumen of each resected intestine was rinsed with 10%
      acetic acid solution and the perfusate was collected. The small intestine
      homogenate was prepared using 30% acetic acid solution. The equivalent samples
      were electrophoresed on 12.5% AU-PAGE and Tricine-16.5% SDS-PAGE, and peptide
      bands were visualized with Coomassie brilliant blue R-250 or ammoniacal silver
      stained respectively. And then analysis of gel imaging and gel overlay assay were
      performed. The bactericidal activity and expressions of AP in the small intestine
      of samples in the two groups were compared. The molecular weight of AP in the
      small intestine was measured. RESULTS: After gastrogavaged with rhubarb
      decoction, changes of AP contents in the small intestine homogenate of mice were
      not obvious, but the molecular weights of AP were different. But the AP contents
      in the small intestine perfusate obviously increased, with the molecular weights
      being 14.3 to 18.4 kDa. But its bactericidal capacity showed no statistical
      difference when compared with that of the control group (P>0.05). CONCLUSION:
      Rhubarb enhanced the expressions of partial APs in the small intestine, which
      might possibly be one of its mechanisms of protecting and strengthening the
      intestinal barrier.

PMID- 21866668
TI  - [Effect of scalp-acupuncture on the proliferation and migration of neural stem
      cells in acute cerebral ischemia/reperfusion injury rats].
AB  - OBJECTIVE: To study the proliferation and migration of neural stem cells (NSCs)
      of acute cerebral ischemia rats and the intervention of scalp-acupuncture (SA),
      and to study its action of mechanism in treating cerebral ischemia. METHODS: One
      hundred healthy Wistar rats were randomly divided into the sham-operation group
      (n = 10), the model group (n = 45), and the SA group (n = 45). The middle
      cerebral artery occlusion (MCAO) model was established using the modified suture
      method. No suture or perfusion was given to rats in the sham-operation group, but
      these rats received the same procedures as those for modeled rats. After modeling
      routine feeding was given to rats in the model group and the sham-operative group
      without any other treatment. SA was successively given to rats in the SA group
      after successful ischemia reperfusion, once daily. Rats were anesthetized and
      sacrificed by peritoneally injecting bromodeoxyuridine (BrdU) at the dose of 50
      mg/kg on the 7th (T1), 14th day (T2), and 28th day (T3) after modeling.
      Neurological severity score (NSS) was assessed. The BrdU positive cells and the
      BrdU/PSA-NCAM positive cells of the dentate gyrus (DG) were counted using
      immunofluorescence assay. RESULTS: Compared with the model group at the same time
      points, the NSS decreased in the SA group. Significant difference was shown at T3
      (P<0.05). Compared with the sham-operative group at the same time point, the BrdU
      positive cells and BrdU/PSA-NCAM positive cells of the model group obviously
      increased. Compared with the model group at the same time point, the BrdU
      positive cells and BrdU/ PSA-NCAM positive cells of the SA group obviously
      increased, showing significant difference (P<0.01). CONCLUSIONS: SA could promote
      the proliferation and migration of endogenous NSCs, which may possibly be one of
      its mechanisms in treating cerebral ischemia.

PMID- 21866669
TI  - [Effects of yiqi huoxue compound combined with exercise therapy on MMP-1 and
      collagen type III expressions of cardiac muscle in chronic heart failure rats].
AB  - OBJECTIVE: To study the effects and mechanisms of Yiqi Huoxue Compound combined
      with exercise therapy on the ventricular remodeling of chronic heart failure
      (CHF) rats after myocardial infarction. METHODS: Eight rats were selected from
      sixty healthy SD rats as the blank control group, and the rest was used to
      prepare CHF rat model by coronary artery ligation in combination with exhausted
      swimming and food reducing. The successfully modeled rats were randomly divided
      into five groups, i. e., the model group (n = 8), the Chinese medicine group (n =
      8), the Western medicine group (n = 8), the Chinese medicine + exercise group (n
      = 10), and the exercise group (n = 10). Routine gastrogavage of equal volume
      distilled water was given to rats in the blank control group and the model group
      respectively, 3 mL each time. Yiqi Huoxue Compound was given by gastrogavage to
      rats in the Chinese medicine group and the Chinese medicine + exercise group at
      the daily dose of 9.2 g crude drug/kg. Lisinopril was given by gastrogavage to
      rats in the Western medicine group at the daily dose of 1.5 mg crude drug/kg. The
      medication was administered twice daily for six successive weeks. The Chinese
      medicine + exercise group and the exercise group adopted exercise therapy, once
      daily. The myocardial tissue of rats' non-infarcted left ventricle was taken out.
      mRNA and protein contents of matrix metalloproteinase-1 (MMP-1) and collagen type
      III were detected by Real-time fluorescent quantitation PCR. RESULTS: Compared
      with the blank control group, the mRNA expression and the average gray value of
      MMP-1 increased, while those of collagen type III decreased in the model group,
      showing statistical difference (P<0.05, P<0.01). Compared with the model group,
      the mRNA expression and the average gray value of MMP-1 decreased in the Chinese
      medicine group, the Western medicine group, and the Chinese medicine + exercise
      group, showing statistical significance (P<0.01). It was lowest in the Chinese
      medicine + exercise group. The mRNA expression and the average gray value of
      collagen type III increased in the Western medicine group and the Chinese
      medicine + exercise group, showing statistical difference (P<0.01). CONCLUSIONS:
      Yiqi Huoxue Compound combined wih exercise therapy could attenuate the
      ventricular remodeling degree. Its mechanism might be to inhibit the MMP-1
      expression, improve the expression of collagen type III, thus alleviating and
      even reversing myocardial fibrosis.

PMID- 21866670
TI  - [Effect and related mechanism of seaweed polysaccharide on apoptosis of
      fibroblast-like synoviocytes in patients with rheumatoid arthritis].
AB  - OBJECTIVE: To study the effect and related mechanism of seaweed polysaccharide
      (SP) on apoptosis of fibroblast-like synoviocytes in patients with rheumatoid
      arthritis (RA-FLS). METHODS: RA-FLS were in vitro cultured using modified tissue
      culture method. Effect of SP (0, 15, 20, and 25 mg/mL, respectively) at different
      time points (0, 3, 4, and 5 days, respectively) on the proliferation and
      apoptosis of RA-FLS, and protein expressions of Caspase-3, Bax, and Bcl-2 was
      detected by cell counting kit-8 (CCK-8) assay, Hoechst 33258 staining assay,
      TUNEL assay, and Western blot, respectively. RESULTS: Compared with 0 mg/mL SP at
      the same time point, the proliferation of RA-FLS was inhibited, and the apoptosis
      was promoted 3, 4, and 5 days after intervened by 15, 20, and 25 mg/mL SP,
      respectively (P<0.01) in time- and dose-dependent manners. RA-FLS Bax protein
      expression was up-regulated, Bcl-2 protein expression down-regulated, Caspase-3
      activated and split by 15, 20, and 25 mg/mL SP, respectively for 4 days (P<0.05,
      P<0.01). Besides, the changes were in a dose-dependent manner. CONCLUSIONS: SP
      could inhibit RA-FLS proliferation and induce its apoptosis in dose- and time
      dependent manners. Its apoptosis mechanism might be through up-regulating
      intracellular Bax protein expression and down-regulating Bcl-2 protein
      expression, thus influencing the mitochondrion signaling pathway, further
      promoting Caspase-3 activation and split, resulting in the apoptosis of RA-FLS.

PMID- 21866671
TI  - [Effects of zhenqing recipe and earthworm on the expressions of transforming
      growth factor-beta1 and plasminogen activator inhibitor 1 in renal tissues of
      type 2 diabetic rats].
AB  - OBJECTIVE: To study the effects of Zhenqing Recipe (ZQR) and earthworm on the
      expressions of transforming growth factor-beta1 (TGF-beta1) and plasminogen
      activator inhibitor-1 (PAI-1) in renal tissues of type 2 diabetes mellitus (T2DM)
      rats. METHODS: The T2DM model rats induced by high sucrose/fat feeding and low
      dose streptozotocin injecting were randomly divided into the model group, the ZQR
      group, and the earthworm group. A normal control group was also set up. ZQR
      extract was given at the daily dose of 24 g/kg body weight by gastrogavage to
      rats in the ZQR group. The earthworm extract was given at the daily dose of 2.6
      g/kg body weight by gastrogavage to rats in the earthworm group. Equal volume of
      distilled water was given to rats in the normal control group and the model group
      by gastrogavage. The medication was once daily for 8 successive weeks. The
      fasting blood glucose (FBG), serum PAI-1, 24-h urinary albumin excretion (UAE),
      and endogenous creatinine clearance rate (CCr) were detected. The structural
      changes of renal tissues stained with Periodic Acid-Schiff were observed by light
      microscope. The expressions of TGF-beta1 and PAI-1 were analyzed by
      immunohistochemistry. And the mRNA and protein expressions of TGF-beta1 and PAI-1
      in the renal cortex were detected by Real-time PCR and Western blot respectively.
      RESULTS: Compared with the normal control group, the FBG, serum PAI-1, UAE, the
      mRNA and protein expressions of TGF-beta1, and PAI-1 significantly increased in
      the model group, and CCr obviously decreased (P<0.01). Compared with the model
      group, FBG, serum PAI-1, UAE obviously decreased (P<0.01) and CCr obviously
      increased (P<0.05) in the ZQR group. FBG was not obviously lowered in the
      earthworm group. The serum PAI-1 and UAE both decreased obviously (P<0.05,
      P<0.01) and CCr increased (P<0.05) in the earthworm group. The effects of ZQR
      were superior to the earthworm. The renal pathological changes got improved in
      the ZQR group and the earthworm group. The mRNA and protein expressions of TGF
      beta1 and PAI-1 significantly decreased in the ZQR group and the earthworm group,
      especially in the ZQR group. CONCLUSIONS: Early application of ZQR and earthworm
      in treatment of T2DM rats with nephropathy was effective in protecting the
      kidney. Its mechanism may possibly be correlated with inhibition of TGF-beta1
      expression, resulting in down-regulation of PAI-1 expression. ZQR showed better
      effects than earthworm.

PMID- 21866672
TI  - [Effect of qianyang recipe on correlated indices of hypertension rats of gan-yang
      hyperactivity syndrome].
AB  - OBJECTIVE: To study the effect of Qianyang Recipe (QYR) on the Gan-yang
      hyperactivity syndrome (GYHS), the blood pressure, and correlated vascular
      regulatory factors of hypertension rat. METHODS: Thirty SD rats were randomly
      divided into the normal control group, the model group, and the QYR group, ten in
      each. Hypertension rat model of GYHS was prepared using Aconiti Praeparata
      Decoction plus ephedrine plus salt water. Rats in the QYR group orally took QYR
      physic liquor, while distilled water was given to rats in the normal control
      group and the model group. They were medicated for 28 successive days. The facial
      temperature, the grip strength, and the systolic pressure were determined once
      every 7 days. Rats' irritable degree and feather color were observed and recorded
      once every 14 days. After the last administration the plasma renin (PR),
      angiotensin II (Ang II), aldosterone (ALD), atrial natriuretic peptide (ANP),
      calcitonin gene-related peptide (cGRP) were determined. RESULTS: Compared with
      the model group of the same phase, the facial temperature of rats in the QYR
      group significantly decreased on the 14th, 21th and 28th day after
      administration. The systolic pressure obviously decreased on the 21st day after
      administration. On the 28th day after administration symptoms such as
      irritability, dry hair were improved, and the Ang II level decreased. There was
      significant difference in all these changes (P<0.05, P<0.01). CONCLUSIONS: QYR
      could relieve GYHS rats' symptoms such as facial hotness, irritability, dry hair,
      and so on, and decrease the systolic pressure. Decreased Ang II level might be
      one of its mechanisms.

PMID- 21866673
TI  - [Consensuses on lung cancer treatment by Chinese medicine experts from Beijing
      and Guangzhou and medication features in the North and South China].
AB  - To study the consensuses on lung cancer treatment by Chinese medicine experts
      from North China and South China, and to analyze their medication features from
      viewpoints such as the medication frequency, combination laws, medication
      classification by collecting 800 recipes on the treatment of lung cancer patients
      prescribed by 8 Chinese oncologists from Guanganmen Hospital of China Academy of
      Chinese Medical Sciences, the Affiliated Hospital of Guangzhou University of
      Traditional Chinese Medicine, and Guangdong Provincial Hospital of Traditional
      Chinese Medicine. Results showed that coix seed, poria, pinelliae tuber were the
      three herbs most commonly used in treatment of lung cancer by all experts. They
      generally accepted Pi invigorating and phlegm removing method as the basic
      treatment method for treating lung cancer. Secondly, they usually used white
      peony root, heterophylla falsestarwort root, and ophiopogonis tuber, etc. (with
      higher medication frequency) to nourish yin and moisten Fei. Thirdly, consistency
      was also shown in clearing heat, detoxication, and anticancer. Smilacis glabra,
      Rhizoma Smilacis Glabrae, Herba Hedyotis diffusae, Herba Scutellariae Barbatae
      were herbs used by all experts. However, there were differences between
      oncologists in North China and South China. Oncologists in South China paid more
      attention to heat toxin and blood stasis, while those in North China paid more
      attention to supplementing both qi and yin.

PMID- 21866674
TI  - [Discussion on studies of individualized diagnosis and treatment using
      metabonomics].
AB  - As one of the most active branch disciplines in the systematic biology research
      field, metabonomics has developed rapidly in recent years and become the research
      hotspot at home and abroad. The proposal of individualized diagnosis and
      treatment has emphasized and focused on the effect of internal factors of the
      human body and individual difference on the diagnosis and treatment of disease.
      Since metabonomics reflects that under the joint action of genes and the
      environment, the overall features of individual biological systems and functions
      states, thus, providing a new train of thought and research platform for studying
      individualized diagnosis and treatment. Through discussion of the train of
      thoughts, methods, progress of metabonomics used in studies on individualized
      difference, we believe that metabonomics technologies have a broad prospect of
      application in the individualized diagnosis and treatment. It is promising to
      have significant breakthrough from theory to practice.

PMID- 21866675
TI  - [Analysis on the Chinese medicine syndrome and therapy in patients with coronary
      heart disease after intervention].
AB  - Along with the extensive application of intervention in treating coronary heart
      disease (CHD), problems such as post-interventional restenosis, no reflowing, and
      slow flowing, and so on increasingly emerge. Chinese medicine and pharmacy occupy
      advantages covering preventing post-intervention risk factors, improving and
      relieving patients' symptoms, and so on. It is a good support and supplement for
      routine therapies in modern medicine. Taking the pathological stages of CHD and
      clinical problems of coronary intervention as the breakthrough points, the
      Chinese medical syndromes and correspondent Chinese medicine recipes and herbs
      were preliminarily studied by combining Chinese medicine's recognition and
      clinical observation on coronary intervention.

PMID- 21866676
TI  - [A brief analysis on the compiling, teaching and learning of new edition of
      Pharmacology of Chinese Materia Medica].
AB  - The new edition of Pharmacology of Chinese Materia Medica has broken through the
      previous mode of the teaching materials. It classified traditional Chinese
      medicinal herbs into three categories: the herbs for radical cure depending on
      syndrome differentiation, the herbs for etiological treatment aimed at
      pathogenesis, and the herbs for symptomatic treatment, combined diseases
      differentiation with syndrome differentiation, showing active significance in
      enlightening, guiding the Chinese medicine theory of combining traditional
      Chinese and Western medicine's compiling, teaching, learning and research
      applications.

PMID- 21866677
TI  - [Linguistic gaps between English and Chinese: their application in translation of
      Chinese medicine].

PMID- 21866678
TI  - [Progress of studies on effects of xuezhikang capsule besides lipids regulating].

PMID- 21866679
TI  - [Progress of studies on effects of ligustrazine on blood vessel endothelium
      protection].

PMID- 21866680
TI  - [Physical activity and healthy diet, weight perception and stress in adult
      population in Chile: analysis of the second quality of life and health survey
      2006].
AB  - Chile had a rapid epidemiological and nutritional transition with an increase in
      risk factors for chronic diseases and obesity. Dietary changes have occurred,
      mostly an increase in consumption of foods high in fat, sugar and salt, as well
      as a decrease in physical activity. This has led to a marked increase in obesity
      rates. To learn more on these risk factors for chronic diseases, obesity and
      physical activity, the First Quality of Life and Health Survey (ECVS) was carried
      out in 2000, with a second version in 2006. The objective of this paper is to
      analyze, from data collected by the 2006 survey, the relationship of physical
      activity with the consumption of fruits, vegetables and dairy products, weight
      perception and stress. The 2006 survey included 6.210 subjects with a 10.8% of
      active population and 89.2% of sedentary people. The relationship of activity was
      determined with the consumption of fruits, vegetables, dairy products, weight
      perception and stress, by sex and socioeconomic levels. Results show that more
      than 50% of the active subjects consume fruits and vegetables, and 50% consume
      dairy products every day, with a higher probability of active persons of
      consuming healthy foods than the sedentary ones. Besides, sedentary people
      perceive themselves with more overweight and obesity than the active subjects.
      There was no relationship between physical activity and stress. People with a
      higher socioeconomic level are more active and consume more healthy products.
      These results permit to elaborate targeted policies and programs to improve diet
      and physical activity in the Chilean population.

PMID- 21866681
TI  - [Prevalence of obesity and level of activity physical in school adolescents].
AB  - Prevalence of obesity and level of activity physical in school adolescents. The
      objective of the work was to quantify the prevalence of overweight and obesity in
      a group of students of Ourense and its relation with the physical activity levels
      during school. 111 schoolares in the 5th and 6th year of primary school, with an
      average age of 11.3 years participated. 42.3% were women and 57.7% men. Weight,
      height and body mass (BMI) index were determined. Overweight and obesity were
      defined using as criteria the value of BMI-specific percentiles for age and sex.
      Physical activity (PA) level was assessed using an interview-questionnaire
      designed to be used with Spanish child population. 38.7% of the population
      presented overweight or obesity, and although the prevalence was higher in girls,
      no significant differences for the BMI between sexes were found. Results revealed
      the 61.2% of the adolescents to be inactive or very inactive, this percentage was
      higher for the girls than for the boys; for which the average energy expenditure
      (metabolic equivalent METS expressed in Kcal.kg-1 hour) is significantly smaller
      than the average for boys.

PMID- 21866682
TI  - Overweight and obesity related factors in schoolchildren in Santa Catarina State,
      Brazil.
AB  - The purpose of this study is to determine the correlation of socioeconomic,
      dietary, and anthropometric-nutritional variables of parents and their children
      to overweight (including obesity) in schoolchildren in Santa Catarina State,
      Brazil. This is a transversal study conducted on 4,964, 6 to 10-year-old
      schoolchildren registered in 345 Santa Catarina elementary schools. The following
      data were acquired: the children's current weight and height, birth weight and
      length, duration of breastfeeding, age at which water, herbal tea and other foods
      were introduced to their diet; parental income, education level, age, weight and
      height were also obtained. The prevalence of overweight and obese children were
      estimated by point and by interval with a 95% confidence; prevalence rates were
      obtained based on the Poisson model. An hierarchical approach was used, in which
      variables were adjusted within blocks and included in the model when they
      presented p < 0.05 at the outcome (overweight including obesity). The results
      indicate that 47.8% of the subjects were male. The prevalence of overweight and
      obese students was 15.4% (C195%: 14.4%-16.5%) and 6.1% (C195%: 5.4%-6.7%)
      respectively and were statistically similar among sexes and age ranges. BMI
      values were higher in males and among older children (p < 0.05). After adjustment
      within and among blocks, the variables per capita household income and parents'
      BMI values remained associated with overweight (including obesity). Overweight
      (including obesity) in schoolchildren is associated with a higher per capita
      household income and parental overweight and obesity.

PMID- 21866683
TI  - [Factors associated with overweight in students from tri-border region:
      Argentina, Brazil and Paraguay].
AB  - The Tri-Border Region has several social and health problems among young people,
      however, there are no data about the overweight between adolescents. This study
      investigated the prevalence of overweight and associated factors in students from
      Tri-Border Region: Argentina, Brazil and Paraguay. Study participants were 1.183
      students, ages from 15 to 18 years. The overweight was identified according to
      body mass index cut-off points proposed by the World Health Organization. The
      Global School-Based Student Health Survey questionnaire was used to identify
      sociodemographic (gender and age) and behavioral factors (physical activity
      outside of school, commuting to school, time watching TV and fruits, vegetables,
      sweet, and salty snack consumption) associated with overweight in adolescents. It
      was used the descriptive statistics, analysis of variance, chi-square and binary
      logistic regression, adopting p < 0.05. Thirteen percent of students were
      overweight. Boys were approximately two times more likely to have overweight than
      girls, independently of nationality. Brazilian students that realized passive
      commuting to school and Argentineans students with low consumption of vegetables
      (< 1 time/day) were 2.2 and 2.9 times more likely to have overweight than their
      counterparts who performed active commuting to school and consumed vegetables
      daily, respectively. These results suggest that public policies to combat
      overweight should attention on promoting healthy lifestyle among young people
      from Tri-Border Region.

PMID- 21866684
TI  - Association between calcium intake and colorectal neoplasia in Puerto Rican
      Hispanics.
AB  - Epidemiological studies show that a high calcium intake reduces the risk of colon
      cancer. The objective was to study the association between calcium intake and
      colorectal neoplasia in a clinic-based sample of Hispanics adults from Puerto
      Rico. As part of this cross-sectional study, a total of 433 subjects were
      recruited from surgery and gastroenterology clinics at the University of Puerto
      Rico. Calcium intake was estimated using a food frequency questionnaire (FFQ) of
      calcium rich foods. Socio-demographics, health history and colonoscopy results
      were obtained from the primary study. Chi square and odds ratios (OR) for
      colorectal neoplasia (adenomas and/ or adenocarcinoma) were calculated for total
      calcium, dietary calcium and for calcium supplement use. In total, 312 (72%) from
      433 participants completed the FFQ and had available colonoscopy results; from
      these, 196 (62.5%) were free of neoplasia and 117 (37.5%) had colorectal
      neoplasia. Colorectal neoplasia subjects were older, a lower proportion were
      females and less educated than those without neoplasia (p < 0.01). Total calcium
      intake (median 1180 mg/d) was greater in those free of neoplasia compared to
      colorectal neoplasia subjects (median 1036 mg/d; p<0.05). A high total calcium
      intake and the use of calcium supplements significantly reduced the OR (crude and
      age adjusted) for colorectal neoplasia; although these associations lost
      statistical significance after additionally adjusting for gender and educational
      level. In conclusion, a high calcium intake and the use of calcium supplements
      may be protective against colorectal neoplasia, although a greater sample may be
      required to observe significant associations in a multivariate model.

PMID- 21866685
TI  - [Salt iodination and excessive iodine intake among schoolchildren].
AB  - The objective of the present study was to evaluate the urinary excretion of
      iodine and relate it to the amount present in salt for human consumption. The
      study involved 145 children from two schools: a rural one and an urban one. We
      performed anthropometric measurements and collected a urine sample and a kitchen
      salt sample from each child. In the rural school, 3.38% of children had iodine
      deficiency. However, most of the values of urinary iodine were above 300 microg/L
      (62.03%) and 59.49% of the kitchen salt samples contained 20 to 60 mg iodine per
      kilo of salt. In the urban school, 3.03% of the children had urinary iodine
      excretion of less than 100 microg/L and 90.91% of the children had urinary iodine
      values exceeding 300 microg/L. Ofthis total, 84.85% of the kitchen salt samples
      contained 20 to 60 mg iodine per kilo of salt. Iodine deficiency is controlled in
      this population, with the current reality showing a high prevalence of excess
      urinary iodine.

PMID- 21866686
TI  - [Factors determining the breastfeeding in children attending public and not-for
      profit daycare centers in Sao Paulo, Brazil].
AB  - Cross-sectional study with 270 children and their mothers in eight public and
      philanthropic daycare centers in the city of Sao Paulo, Brazil. The objective is
      to identify the determinants of exclusive breastfeeding (EBF) and breastfeeding
      (BF). The Mann-Whitney/ Wilcoxon test and survival analysis; Kaplan Meier curves
      and Cox multiple regression models were used for statistical analyses. The median
      of exclusive breastfeeding duration was 79.1 +/- 55.6 days and breastfeeding was
      185.3 +/- 174.2 days. In multivariate analysis, the following risk factors of
      early weaning for exclusive breastfeeding were identified: pacifier use (HR =
      1.65, 95% CI = 1.24 to 2.2); previous hospital admission (HR = 1.35, 95% CI =
      1.01 to 1.80); mother working outside home (HR = 1.33, 95% CI = 1.00 to 1.76).
      For breastfeeding were identified: pacifier use (HR = 2.54, 95% CI = 1.87 to
      3.45) and mother who works outside the home (HR = 1.51, 95% CI = 1.14-1.99). The
      results show that it is necessary to continue to promote and support
      breastfeeding, mainly the exclusive breastfeeding until six months of age. The
      daycare centers should incorporate this idea, once they may have direct control
      over some of the early weaning determinants, and are also good places to deliver
      messages and guidance on nutrition education to mothers and caregivers in contact
      with children under three years old.

PMID- 21866687
TI  - [Determination of the concentrations of proteins, carbohydrates and fat in milk
      of mothers in relactation].
AB  - In a prospective, randomized and comparative trial the milk of 40 lactating
      mothers of hospitalized children at the Department of Pediatrics, University
      Hospital in Maracaibo, Venezuela was analyzed in a year period. They were divided
      in two groups of 20 mothers each: Group A, mothers in a relactation situation,
      and Group B (Control): Exclusive breastfeeding. Both types of milk were analyzed
      in a blind fashion to determine fat, proteins and carbohydrates. Results show
      that fat concentration (g/dL) was significantly more concentrated in Group B than
      in A, from 3.6 +/- 1.5 to 5.5 +/- 1.0 (p < 0.001), while in contrast, the
      carbohydrates concentration (g/dL) was decreased from 6.4 +/- 5.7 to 5.7 +/- 0.8
      (p < 0.001). Moreover, proteins concentration (g/dL) was not significantly
      modified, since in group A it was 2.1 +/- 1.2 as compared to group B (2.4 +/-
      0.3.) Caloric value was also significantly decreased from the control value of
      83.2 +/- 9.4 to 66.7 +/- 17.8 in the relactation group (p < 0.001). In
      conclusion, it a clear difference between the two types of milk in this study.

PMID- 21866688
TI  - Health-related fitness in school children: compliance with physical activity
      recommendations and its relationship with body mass index and diet quality.
AB  - This study establishes the relationship between the compliance with the
      governmental physical activity guidelines (at least a minimum of one hour of
      moderate to vigorous physical activity, MVPA, five times a week), health-related
      physical fitness and different health related lifestyle variables in a
      representative sample of Spanish children. Subjects were a representative group
      of scholars from five schools randomly selected in Extremadura, a mainly rural
      region with a very low population density. Statistical analysis comprises a t
      test to calculate physical fitness differences between groups, according to the
      compliance with the mentioned physical activity guidelines. A multinomial
      logistic regression coefficient is established to determine the differences
      between the better physical fitness status group (= percentile 75) and the poorer
      physical fitness status group (= percentile 25) for each fitness test and gender,
      body mass index, physical activity, Mediterranean diet index and population size.
      Main findings show that the compliance with physical activity guidelines result
      in a better handgrip strength in left hand (p < 0.05), leg strength (p < 0.000),
      speed-agility run (p < 0.000) and 20 m endurance shuttle run (p < 0.000). Being a
      girl, being overweighed and living in an urban setting are associated with a
      lower physical fitness (= percentile 25), whereas there is no relationship
      between diet quality and subjects' performance in all physical fitness test
      evaluated. As a conclusion, this study emphasizes the need to promote an active
      lifestyle in which physical activity suppose a minimum of one hour of regular
      MVPA, at least five times a week, to achieve a healthy fitness status.

PMID- 21866689
TI  - [Acceptance of yoghurt with different functional ingredients among consumers in
      supermarkets in southern Chile].
AB  - In view of the interest in the role of foodstuffs in improving wellbeing and
      health, the object of this study is to distinguish consumer typologies in Temuco,
      La Araucania Region, Chile, according to their preferences for different
      functional ingredients, flavouring, colouring and price in yoghurt. A semi
      structured survey was applied to 400 supermarket customers. The respondents
      ordered eight alternative yoghurts according to their preferences, with different
      functional ingredients (fibre, antioxidants), flavourings (sugar, sweetener),
      colouring (natural, artificial) and three price options, for a conjoint analysis
      with fractional factorial design. Variables affecting knowledge of "functional
      food" were evaluated using a binomial logit model. It was determined by conjoint
      analysis that in general a preference existed for yoghurt containing fibre,
      sweetener, natural colouring, and at the lowest price. Three typologies were
      distinguished by analysis of hierarchical conglomerates: the majority segment
      (48.8%) displayed a greater preference for fibre; the second (41.7%) also
      preferred fibre, but gave first priority to artificial colouring and preferred a
      higher price. The minority (9.5%) was the only segment to prefer antioxidants.
      The typologies differed significantly in satisfaction with their food-related
      life, knowledge of the function of fibre and presence of cancer and obesity in
      some member of the respondent's family. The binomial logit model was significant
      (P < 0.01), indicating that if the consumer has a job or has had access to
      information on functional foods, the probability increased of knowledge of what
      these mean. There was thus majority acceptance of yoghurt enriched with fibre and
      with added sweetener.

PMID- 21866690
TI  - [Evaluation of the polymerase chain reaction (PCR) for the detection and
      identification of Listeria monocytogens in fresh cheese coming from the
      metropolitan area of San Jose, Costa Rica].
AB  - Food borne diseases are very important worldwide and their frequency is still
      high despite the different efforts focused in diminishing their morbidity and
      mortality. Listeria monocytogenes is one of the agents associated in this kind of
      diseases. In the lactic industry, this bacteria is important since raw milks as
      well as dairy products have been associated in outbreaks, being fresh cheese one
      of the most vulnerable products to the contamination with this bacteria. The
      traditional identification of the bacteria is done by a laborious, time consuming
      and low sensitive technique and the polymerase chain reaction may allow more
      precise and exact results in shorter time. For this reason the objective of the
      present study was to optimize the procedure to determine the sensitivity and
      specificity limits for the detection of L. monocytogenes from fresh cheese and
      the predictive value of the test. In order to achieve this objective, 76
      pasteurized cheese samples were evaluated (45 samples were artificially
      inoculated at the lab and 31 were used as negative controls). The validation of
      the technique was done in 50 samples of non pasteurized fresh cheese. Traditional
      culture isolation was performed according to the methodology described in
      Compendium of Methods for the Microbiological Examination of Foods. PCR reaction
      for the detection of L. monocytogenes was based on the methodology described by
      Poutou,using primers characteristic of the genus and the listeriolisine O gene
      that is specie's specific. The optimal incubation period determined for the
      selective enrichment broth was of 48h, and a 100% sensitivity, specificity,
      predictive value (positive and negative) were obtained by PCR. The technique
      validation showed the specificity ofthe test in the detection of only the L.
      monocytogenes species, and not other genus or species that may appear in food
      matrixes or in food environments.

PMID- 21866691
TI  - [Fatty acids profile characterization of white maize hybrids grown in Venezuela].
AB  - In Venezuela, white corn is the most important crop regarding production, harvest
      area and consumption. One of its main by-products is corn oil, whose positive
      effect on health caused by the high content of unsaturated fatty acids has been
      widely recognized. In order to characterize the fatty acids profile of twelve
      white grained maize hybrids extensively grown in Venezuela, and the effect that
      divergent localities has on this profile, three semi commercial scale trials
      where established in Portuguesa, Yaracuy and Guarico states. Proportions of the
      main fatty acids in the raw oil of the different grain samples were determined
      using gas chromatography. Significant differences (p < 0,01) between hybrids were
      found for arachidic, palmitic, stearic, oleic, gadoleic and linoleic acids; non
      significant differences were found for linolenic acid. Significant differences
      between localities were found for all the fatty acids evaluated. High and
      significant correlations between fatty acids content were found; the most
      important relations were: linoleic-oleic (Rho = -0,98**), arachidic-palmitic (Rho
      = -0,61**), linoleic-stearic (Rho = -0,61**) and oleic-stearic (Rho = 0,58**).
      Corn produced in Venezuela presents lower levels of linoleic and higher levels of
      palmitic, stearic and oleic acids than the levels found in temperate corn. These
      differences involve significant changes in the nutritional properties of
      Venezuelan corn oil that should be considered in the development of new cultivars
      and industrial processes for oil production.

PMID- 21866693
TI  - [Microbial metabolic characteristics and ecological controlling in petroleum
      reservoir--a review].
AB  - Petroleum reservoir has a variety of microbes with diverse metabolic
      characteristics and great diversity. These microbes play an important role in
      geochemical cycle. Research on their metabolism and ecological relationships
      enables the understanding of Microbial Enhanced Oil Recovery (MEOR). Based on the
      present researches, we review the microbial metabolic characteristics and
      ecological relationships in oil reservoir.

PMID- 21866692
TI  - Bioactive indicators related to bioelements of eight unifloral honeys.
AB  - Honey is the most popular bee product used by man, with nutritional and medicinal
      purposes. Its great diversity is attributed to numerous factors (bee type,
      visited flora, environment, and management). The quality of honey is controlled
      with routine parameters (free acidity, diastase activity, reducing sugars, ash,
      water, hydroxymethyfurfural, and sucrose contents). Besides the biochemical
      quality control, a functional profile is also important for pharmacological
      applications. In this work, bioactive indicators such as the antioxidant
      activity, flavonoid and polyphenol contents were evaluated by spectrophotometry,
      and correlated to the content of six bioelements (Ca, Cu, Fe, Mg, Mn, Zn)
      measured by atomic absorption spectroscopy, tandem FI-FAAS, in 14 unifloral Czech
      honeys. The antioxidant activity was 43.13 +/- 53.72 micromoles TEAC/100 g honey.
      The flavonoid content was 5.18 +/- 4.19 mg QE/100 g, and the polyphenol content
      was 45.38 +/- 27.20 mg GAE/100 g. Buckwheat honey showed the highest values for
      these indicators of bioactivity, the acacia honeys the lowest, and the rest of
      the honeys were comprised between both of them. Honey content of bioelements was
      138.19 +/- 55.57 ppm Ca (min 77.11-max 261.65), 0.33 +/- 0.41 ppm Cu (min 0.00
      max 1.37), 2.95 +/- 1.10 ppm Fe (min 1.34-max 5.36), 35.08 +/- 29.59 ppm Mg (min
      8.76-128.06), 4.93 +/- 3.99 ppm Mn (min 0.34-max 11.31), 1.07 +/- 0.56 ppm Zn
      (min 0.49-max 2.52). The antioxidant activity of honey was significantly
      correlated to its content of cupper, iron, magnesium, manganese and zinc, but was
      not correlated to calcium.

PMID- 21866694
TI  - [Progress in biosynthesis of epsilon-poly-L-lysine and genetic transformation for
      epsilon-poly-L-lysine producer--a review].
AB  - Epsilon-Poly-L-lysine (epsilon-PL) is a polymer with strong antimicrobial
      activity and consists of 25-35 L-lysine monomers linked via epsilon-amino-alpha
      carboxyl peptide bond. This polymer is one of only two homo-poly (amino acid)
      polymers known in nature. To date, the biosynthesis mechanism of epsilon-PL was
      remained unclear. Recently, epsilon-PL synthetase was identified as a
      nonribosomal peptide synthetase and it utilized L-lysine to synthesize epsilon
      PLs of various chain length by iteratively condensing reaction, which was similar
      to type I polyketide synthase and was not determined by epsilon-PL-degrading
      enzyme. Meanwhile, the shutter vectors pLAE001 and pLAE003, special for epsilon
      PL producer have been constructed, which is significant for studying epsilon-PL
      biosynthesis. In this review, the biosynthesis of epsilon-PL and the genetic
      transformation were introduced. Also, the study in our group was presented and
      the views related to e-PL study were raised. Finally, the prospect of application
      of combinational biosynthesis in epsilon-PL-producing strain improvement was also
      discussed considering epsilon-PL synthetase is a nonribosomal peptide synthetase
      containing several modules.

PMID- 21866695
TI  - [Pullulanase and the proteins related to its secretion--a review].
AB  - Due to its ability of hydrolyzing alpha-1,6-linkages, pullulanase plays a
      significant role in the industries where starch is used as raw material,
      including food processing and bioenergy. Exploitation of this enzyme focuses not
      only on screening novel strains, but also on its molecular structure as well as
      its secretion pathway and improvement of the properties. Therefore, researches on
      the gene regulation and the proteins involved in the secretory pathway seem
      especially important. This review introduced the advances in the study of these
      fields.

PMID- 21866696
TI  - [Genetic diversity of major capsid genes (g23) of T4-type bacteriophages in
      natural environments--a review].
AB  - During the past two decades, the genetic diversities of bacterial and fungal
      communities and their relationship with the inhabited environments were
      intensively studied with the development of molecular biological techniques.
      However, although bacteriophages are ubiquitous and more abundant than their
      hosts in biosphere, their diversity is still little known. In this paper, we
      targeted the major capsid genes (g23) of T4-type bacteriophages and reviewed the
      recent progress on their genetic diversity. The distribution of g23 of T4-type
      bacteriophages was distinctly different among natural environments of marines,
      lakes and paddy fields, and the majority of g23 were grouped into several novel
      clusters according to their obtained environments. In addition, several research
      tips and future research tendencies for the study of environmental g23 were also
      addressed.

PMID- 21866697
TI  - Snf1/AMPK protein kinase modulates cell wall integrity in the human pathogenic
      yeast cryptococcus neoformans.
AB  - OBJECTIVE: The Snf1/AMPK family of protein kinases is highly conserved among
      eukaryotes. Our previous study showed that Cryptococcus neoformans SNF1 played
      critical roles in the production of virulence factors and virulence itself. In
      this paper, we report a novel function of SNF1 in cell wall integrity. METHODS:
      We used Calcofluor white staining epifluorescence microscopy to evaluate the cell
      wall integrity and cell segregation; tap water with constant flow rate and
      pressure to wash yeast colonies to evaluate cell-to-agar adhesion capability;
      growth on Sodium dodecyl sulfate (SDS), Congo red and Fluorescent Brightener 28
      containing agar to examine cell wall integrity. RESULTS: The disruption mutant of
      SNF1 was sensitive to SDS and Congo red, suggesting impairments in the cell wall.
      The mutant cells showed abnormal separation, defects in adhesion to agar surface,
      and growth defects at high temperature which could be suppressed by osmotic
      stabilization. CONCLUSION: C. neoformans SNF1 was essential for cell wall
      integrity that was likely responsible for normal adhesion of the cells to agar
      and resistance to heat.

PMID- 21866698
TI  - [Soil bacterium Pseudomonas sp. 593 synthesizes phosphatidylcholine via
      phosphatidylcholine synthase pathway].
AB  - OBJECTIVE: Prokaryotes synthesize phosphotidylcholine by using phospholipid N
      methylation or phosphatidylcholine synthase pathway or both. To confirm which
      pathway the soil bacterium Pseudomonas sp. 593 utilizes, we tested its
      phosphotidylcholine synthesis, cloned the pcs gene encoding phosphatidylcholine
      synthase, examined Pcs activity, and constructed a pcs mutant. METHODS: To clone
      the pcs gene from Pseudomonas sp. 593 genomic DNA, we firstly aligned amino acid
      sequences of phosphatidylcholine synthases in different pseudomonas strains
      reported in databases. Then we designed degenerate primers based on two amino
      acid segments conserved in sequences of phosphatidylcholine synthases. A partial
      fragment of the pcs gene was finally amplified from Pseudomonas sp. 593 genomic
      DNA. The amplified partial fragment was labeled with digoxigenin-dUTP (DIG) as a
      probe, sub-cloning library of Pseudomonas sp. 593 genomic DNA was prepared and
      then screened using DIG-labelled probe via in situ colony hybridization. DNA
      homologous recombination in vivo was preformed to delete pcs gene of Pseudomonas
      sp. 593. Thin-layer chromatography (TLC) assay was used to analyze total
      phospholipids, detect phosphotidylcholine content and determine pcs gene
      activity. RESULTS: TLC analysis revealed that Pseudomonas sp. 593 growing in the
      M9 or LB medium with choline was able to synthesize phosphotidylcholine, but
      wasn't without addition of choline. A 894 bp DNA fragment coded a protein with
      phosphatidylcholine synthase activity was cloned from Pseudomonas sp. 593. The
      pcs mutant obtained from in vivo mutagenesis was unable to form
      phosphotidylcholine, no matter choline was presented in the medium or not.
      CONCLUSION: Phosphatidylcholine synthase pathway is a sole way for
      phosphotidylcholine synthesis in soil bacterium Pseudomonas sp. 593 or other
      Pseudomonas strains.

PMID- 21866699
TI  - [Formation of Aspergillus niger-mineral aggregation and characterization of
      polysaccharide from aggregation].
AB  - OBJECTIVE: In order to understand the weathering on potassium-bearing mineral by
      Aspergillus niger, we studied the formation of A. niger-mineral aggregation and
      polysaccharide in the revolving and fermenting mode and their role in the process
      of weathering on potassium-bearing mineral. METHODS: We used four different media
      to study the morphology of A. niger-mineral aggregation; ultraviolet-visible
      spectrum (UV-Vis) , fourier transform infrared spectrum (IR), gas chromatography
      (GC), scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS)
      were combined to research the changes of polysaccharide and their significances
      in the micro-environment forming fungal-mineral aggregation. RESULTS: A. niger
      myclia intertwined, adsorbed and bonded mineral powder to form aggregation by the
      assistance of polysaccharide and other metabolites. After formation of the
      aggregation, the concentration and structure of polysaccharide were changed
      significantly. CONCLUSION: The changes of polysaccharide would enhance the
      adsorption on minerals, chelation on metal ions and adsorption on water
      molecules, which provided a favorable micro-environment for the fungal using
      mineral nutrients effectively.

PMID- 21866700
TI  - [Active ingredients and efficacies of Ganoderma lucidum cultivated on non
      medicinal parts of Chinese medicinal herbs].
AB  - OBJECTIVE: Ganoderma lucidum was cultivated on non-medicinal parts of Salvia
      miltiorrhiza, Chrysanthemum morifolium, Ptatycodgn grandlfiorum, as all are
      Chinese traditional herbal medicines. We studied the changes of active
      ingredients and efficacies of the Ganoderma lucidum fruit bodies. METHODS: The
      agronomic characters, polysaccharide and terpene contents, acute toxicity and
      efficacy of Ganoderma lucidum grown on the non-medicinal part of the three
      materials were compared with that grown on the ordinary formula group (OF. G)
      which was composed of corn cob, cotton seed shell. RESULTS: Biological conversion
      efficiencies of the Ganoderma lucidum fruit body using non-medicinal parts were
      higher than that of using the ordinary formula group (OF. G), though growth
      periods became longer; Contents of active ingredients were all improved except
      that the terpene content of the Salvia miltiorrhiza group was decreased. Both
      polysaccharide and terpene from the Chrysanthemum morifolium group were the
      highest, contents of which were respectively 2.47% and 0.79%; Acute toxicity test
      showed that Ganoderma lucidum fruit bodies were all with low toxicities. Mice
      maximum tolerance dose were 100 g/kg weight. In hemolysin test and sleeping
      promotion test, the Chrysanthemum morifolium group showed better effect than the
      ordinary formula group (OF. G). In anti-fatigue test, only the ordinary formula
      group (OF. G) proved to be more effective. CONCLUSION: It's feasible to cultivate
      Ganoderma lucidum and active ingredients and efficacies of Ganoderma lucidum have
      been changed using the non-medicinal parts of Chinese medicinal herbs.

PMID- 21866701
TI  - [Involvement of quorum-sensing in biosynthesis of polyhydroxyalkanoates in
      Pseudomonas aeruginosa].
AB  - Quorum-sensing (QS) is a regulatory mechanism with which bacteria regulate the
      gene expression according to their population density. Pseudomonas aeruginosa
      regulates the expression of multiple genes via a hierarchical quorum-sensing
      cascade through LasR and RhlR and their cognate signal molecules N-(3
      oxododecanoyl)-L-homoserine lactone (30-C12-HSL) and N-(butanoyl)-L-homoserine
      lactone (C4-HSL). OBJECTIVE: It aims to explore the regulation of QS on
      biosynthesis of polyhydroxyalkanoates (PHA) in P. aeruginosa. METHODS: Wild-type
      P. aeruginosa PA01 and its QS mutants were used to investigate the effects of
      quorum-sensing on biosynthesis of PHA by GC and real-time PCR at physiological
      and molecular level. RESULTS: After treated with QS signal molecule synthesis
      inhibitor azithromycin, the accumulation of PHA significantly decreased in P.
      aeruginosa PA01 and its QS mutant strains. The content of PHA in C4-HSL synthase
      gene rhlI mutant strain PA0210 had no significant difference compared with that
      of the wild type. However, the PHA contents were significantly affected in 30C12
      HSL synthase gene lasl mutant strain PA055, 30C12-HSL transcriptional regulator
      gene lasR mutant strain PA056 and lasI/lasR double mutant strain PA057. PHA
      synthase gene phaC1 expression exhibited a significant reduction in lasI mutant
      and lasR mutant strains. 30C12-HSL signal molecules complementary experiment
      shows that the expression of phaC1 can be recovered to the level of the wild
      type, but the synthesis of PHA is only partially restored in lasI mutant strain.
      CONCLUSION: The results implicates that lasI/lasR system might be involved in the
      regulation of intracellular PHA biosynthesis in P. aeruginosa PA01.

PMID- 21866702
TI  - [Reactivity and function of cysteine residues in imidase from Pseudomonas putida
      YZ-26].
AB  - OBJECTIVE: We investigated the reactivity and function of two cysteine residues
      in imidase (CIH) by site-directed mutagenesis. METHODS: Three variants of imidase
      (CIH) were constructed with Cys7 and Cys108 or only one of them substituted with
      Gly. The two thiol groups of Cys7 and Cys108 of imidase were specifically
      modified separately or collectively by dithio-bis-nitrobenzoic acid (DTNB) in the
      native state. It was also confirmed by SDS-PAGE analysis. To further verify the
      above results, the oligomeric structure and sulfhedryl groups of native and
      mutant CIH were also examined by measuring zinc binding ability and molecular
      size under different concentrations of H2O2. RESULTS: Compared with CIH, CIH108
      retained 72% activity, while CIH7, 108 and CIH7 had no activity using DL
      hydantoin as substrate. The spectral detection result shown that the two thiol
      groups were both in a free state. It is indicated that CIH and CIH108 are
      tetramer, CIH7,108 is multimer, and CIH7 is a mixture of monomer and multimer.
      The zinc binding ability of CIH108 was still relative high, while CIH7 and
      CIH7,108 decreased obviously. The increased concentration of H2O2 could increase
      the intrachain disulfide bond of CIH and the interchain disulfide bond of CIH108.
      CONCLUSION: All data imply that the Cys7 is required for binding zinc ion and
      maintaining the stable structure of enzymatic molecule.

PMID- 21866703
TI  - [Broader substrate specifity of Candida parapsilosis SCR II for catalyzing
      acetophenone derivatives by site-directed mutagenesis].
AB  - OBJECTIVE: The function for catalyzing acetophenone derivatives of short-chain
      carbonyl reductase II (SCR II) from Candida parapsilosis was modified by site
      directed mutagenesis. METHODS: An important site (E228) was selected for
      mutagenesis through amino acid sequence and protein structure alignment, and the
      corresponding variant E228S was constructed in E. coli. Using the acetophenone
      derivatives as substrates, we determined specific activities and
      biotransformation function of the variant. RESULTS: The specific activity of the
      variant E228S was reduced to 25% of the wild type for 2-hydroxyacetophenone
      reduction. However, it increased approximately 7-20 times for acetophenone, 4'
      methylacetophenone and 4'-chloroacetophenone. The biotransformation results
      showed that the variant catalyzed the transformation of (S)-1-phenyl-1,2
      ethanediol in a yield of less than 10%, while exhibited excellent performance to
      afford (R)-1-phenethylethanol, (R )-1-(4-methylpheyl) ethanone and (R)-1-(4
      chlorophenyl) ethanol from acetophenone, 4'-methylacetophenone and 4'
      chloroacetophenone with high optical purity of 99% in a yield of above 80%.
      CONCLUSION: We broadened the substrate specificity and catalytic function of SCR
      II by replacement of the critical amino acid (E228) inside the substrate binding
      pocket, which provided a novel approach for rational modification of short-chain
      carbonyl reductases, making it as a potential tool for asymmetric reduction and
      chiral alcohol preparation.

PMID- 21866704
TI  - [Expression and subcellular localization of (R)- and (S)-specific carbonyl
      reductases from Candida parapsilosis in Saccharomyces cerevisia].
AB  - OBJECTIVE: The (R)- and (S)- specific carbonyl reductases (RCR and SCR) with
      enhanced green fluorescence protein ( EGFP) were expressed in Saccharomyces
      cerevisiae W303-1A. By analysis of EGFP expression spectrum, the protein
      distribution and subcellular localization of two enzymes were determined.
      METHODS: By SOE-PCR method, the fused genes of RCR and SCR with EGFP were cloned
      and constructed on an eukaryotic expression vector pYX212, and transformed into
      S. cerevisiae by electroporation. With fluorescent protein as selection marker,
      the expression and distribution of RCR and SCR were observed. RESULTS: The EGFP
      expression in S. cerevisiae cells was observed under the laser scanning confocal
      microscopy. It was showed that the two enzymes expressed stably in S. cerevisiae
      and mainly distributed in the intracellular membrane and cytoplasm, while
      minority were dotted in the center of cells. According to the fluorescent
      intensity, the expression level of SCR was much higher than that of RCR in S.
      cerevisiae. The biotransformation results showed that the fused proteins EGFP-RCR
      and EGFP-SCR reduced 2-hydroxyacetophenone to give (R)- and (S)-1-phenyl-1 ,2
      ethanediol (PED) respectively, with the optical purity of 86.6% in a yield of
      70.4% for the former enzyme and with the optical purity of 92.3% in a yield of
      81.8% for the latter one. DISCUSSION: The fusion of RCR or SCR with EGFP showed
      no effect in protein conformation and biological activity. When compared with the
      recombinant Escherichia coli harboring RCR or SCR, the genetically engineered S.
      cerevisiae had obvious advantages in the biological function. The study provided
      the solid foundations for visible research of functional expression controlling
      and subcellular localization of carbonyl reductases.

PMID- 21866705
TI  - [Effect of flooding time on community structure and abundance of Geobacteraceae
      in paddy soil].
AB  - OBJECTIVE: The dynamic characteristics of community structure and relative
      abundance of Geobacteraceae were investigated to understand their response to
      microbial iron (III) reducing in flooded paddy soil. METHODS: The paddy soil was
      incubated anaerobically and the amount of Fe(II) was determined during the
      flooding incubation. We retrieved Geobacteraceae sequences from clone libraries
      constructed for different time points (1 h and day 1, 5, 10, 20 and 30) after
      flooding of the paddy soil. The diversity and community structure were analyzed
      by using RFLP method, and the relative abundance of Geobacteraceae was detected
      by real-time PCR. RESULTS: Microbial reduction of iron (III) changed greatly in
      early time and was stable after incubated for 20 d in paddy soil. The largest
      iron reduction potential was 10.16 mg/g with a Vmax of 1.064 mg/(g x d) at the
      time of 4.84 d whereas this process achieved plateau after 20 days flooding.
      Diversity of Geobacteraceae, given by alpha indices, fluctuated during the
      flooding incubation. Two peaks of diversity were observed in treatments of 5 d
      and 20 d respectively, while significant low diversity appeared in samples of 10
      d and 30 d. Beta indices described the differences between community structures
      of Geobacteraceae and hence reflected the variation of the flooding situation
      over time. In all samples, 10 RFLP-based preponderant types were found, which
      fell into clade 1 and clade 2 of Geobacteraceae. The relative abundance of
      Geobacteraceae was the lowest in 1 d (1.20% ) and the highest in 20 d (4.54%).
      CONCLUSION: The dynamic variation of Geobacteraceae diversity, community
      structure and abundance are closely related to microbial iron (III) reducing in
      flooding paddy soil.

PMID- 21866706
TI  - [Isolation and toxogenic characterization of tri5 positive Fusarium from poultry
      houses].
AB  - OBJECTIVE: We used tri5-PCR technique to identify the toxin-producing Fusarium
      strains, the toxogenic characteristics and toxicogenic condition of tri5 positive
      strains. We also evaluated the potential trichothecene-producing level of the
      Fusarium strains from the air and solid materials in poultry houses. METHODS:
      tri5 gene, the start gene encoding trichothecene synthase, was taken to detect
      139 Fusarium isolates by PCR. Toxogenic culture was carried out for tri5 positive
      Fusarium strains, and the quantities of T-2 and HT-2 toxins in toxogenic cultures
      were measured by high performance liquid chromatography (HPLC) after immune
      affinity column clear-up. RESULTS: Among the 42 tri5 positive strains determined
      by tri5-PCR, all 10 tri5 positive strains from the air in poultry houses were
      found to produce T-2 toxin (1.36-5 ng/mL) or HT-2 toxin (6.1-17.1 ng/mL) after
      culture. The optimal conditions for toxogenic culture were 9 days of culture with
      5 degrees C-20 degrees C temperature fluctuation and light-dark alternating at 24
      h intervals, shaking at early stage and non-shaking at later stage. The toxin
      production of tri5 positive strains was significantly affected by temperature and
      time, but it has no correlation with the dry mass of mycelium. CONCLUSION: In
      comparison with the traditional method, tri5-PCR is a rapid method for accurate
      detection of toxogenic Fusarium isolates in large amounts of environmental
      samples from poultry houses. The results provide a technical support and
      theoretical basis for early hazard warning and control of toxogenic Fusarium
      strains in animal raising environments.

PMID- 21866707
TI  - [Distribution of microbes and their hereditary diversity in the rhizosphere of
      carnation in greenhouse].
AB  - OBJECTIVE: To investigate the relationship between microbial community and the
      blight diseases in rhizosphere of carnation for biological control. METHODS:
      Bacterial strains isolated from the rhizosphere of healthy and blight carnation
      plants in greenhouse were replicated by morphology and 16S rRNA gene similarity,
      and investigated by using phylogenetic analysis based on 16S rRNA gene sequence
      alignments. RESULTS: Isolates belonged to 4 phyla of bacteria, 65 isolates from
      the samples of healthy carnation plants belonged to 9 genera and Bacillus,
      Streptomyces, Mortierella were the dominant bacteria. However, 33 isolates from
      the samples of blight carnation plants belonged to 12 genera and
      Stenotrophomonas, Sphingobacterium, Pseudomonas, Chryseobacterium, Amycolatopsis
      and Fusarium were only isolated from the sample of blight carnation plants. At
      least 13 isolates should represent potential novel species based on lower
      similarities of 16 S rRNA gene (90%-98% ). CONCLUSION: The result showed that
      either the percentage of the fungus in the total strains or the abundance of
      Bacillus groups in the total strains can be the referential targets to evaluate
      whether the carnation soil would be healthy for the carnational growth or lead to
      fusarium wilt diseases, accurately forecasting potential risks of the disease.

PMID- 21866708
TI  - [Specificity comparison of three Feacalibacterium prausnitzii-specific PCR primer
      pairs].
AB  - OBJECTIVE: To compare the specificity of three 16S rRNA gene-based PCR primer
      pairs (FPR-1/FPR-2, FPR-2F/Fprau645R and Fprau223F/Fprau420R), which are used to
      specifically detect and quantify the important human gut bacterium
      Feacalibacterium prausnitzii. METHODS: Clustal X was used to align the sequences
      of individual primer and the 16S rRNA gene of F. prausnitzii and other bacteria.
      The number of Faecalibacterium spp. sequences in Ribosomal Database Project (RDP)
      matched by each primer was obtained by the Probe Match tool. With the full-length
      16S rRNA gene clone library constructed by our laboratory which contained 7255
      clones from the gut microbiota of 7 Chinese people, the Simulated PCR (SPCR)
      program was applied to predict the clone number of F. prausnitzii and other gut
      bacteria matched by every primer pair; PCR amplification was performed with three
      primer pairs and representative clones to verify the SPCR prediction. Real-time
      quantitative PCR was performed with three primer pairs, respectively, for fecal
      samples from 14 healthy individuals. RESULTS: The first base at the 3' end of
      Fprau645R showed the highest mismatch level for non-F. prausnitzii bacteria. The
      percentage of the number of Faecalibacterium spp. sequences matched by Fprau645R
      accounting for that of matched bacteria sequences in the RDP database was 97.6%,
      which was significantly higher than that of other primers. As SPCR predicted, all
      three primer pairs can detect about 1171 clones from F. prausnitzii; the clones
      of non-Faecalibacterium spp. detected by FPR-2F/Fprau645R mainly were
      Subdoligranulum spp. , but the non-Faecalibacterium spp. clones detected by FPR
      1/FPR-2 and Fprau223F/Fprau420R were mainly Subdoligranulum spp., Oscillibacter
      spp. , Ruminococcus spp. and unclassified Ruminococcaceae etc. The real PCR
      showed the same results with SPCR. The real-time quantitative PCR showed FPR
      1/FPR-2 and Fprau223F/Fprau420R detected more bacteria than FPR-2F/Fprau645R.
      CONCLUSION: The three primer pairs can detect F. prausnitzii and Subdoligranulum
      spp., however, the specificity of FPR-2F/Fprau645R is better than FPR-1/FPR-2 and
      Fprau223F/Fprau420R.

PMID- 21866709
TI  - [Population characterization of Balantidium coli from pigs using ITS1-5.8S rRNA
      ITS2 sequence].
AB  - OBJECTIVE: To determine the species and genotypes of Balantidium isolated from
      pigs in Henan province, China. METHODS: Scatoscopy and the modified DMEM media
      were used to isolate trophozoites of Balantidium from pig feces. The ITS1-5.8S
      rRNA-ITS2-based molecular marker method, Acridine orange staining ( AO) and
      microscopic observation were used to determine the population characteristics
      among different isolates of B. coli from various pigs farms. RESULTS: We isolated
      15 isolates from the pigs at diagnosis in the Animal Hospital of Henan University
      of Science and Technology from the pig farms of the 8 counties or cities of the
      west of Henan province in total, and all of them belong to the same species B.
      coli. MJ-2 and SX-1 isolates were genotype A of B. coli, and the remaining 13
      isolates were genotype B. Trophozoites of MJ-2 and SX-1 were bigger, moved more
      slowly and lower density in feces and in vitro culture than other 13 isolates,
      while structures of their nuclei were not different. CONCLUSION: Both genotype A
      and B of B. coli are present in the pig farms of the west of Henan province,
      China, and genotype B is the determinant population in pigs farms. These findings
      could provide an important implication for the effective control of balantidiosis
      of human and other hosts.

PMID- 21866710
TI  - [Isolation and identification of dominant microorganisms in rhizosphere of
      continuous cropping with peanut].
AB  - OBJECTIVE: We isolated and identified dominant microorganisms from the
      rhizosphere of continuous cropping with peanut, to study the relationship between
      dominant microorganisms and peanut continuous cropping. METHODS: By using
      dilution-plate method we isolated dominant bacteria, dominant fungi and
      actinomycetes from the rhizosphere of continuous cropping with peanut.
      Morphological specificity, culture shape, physiological-biochemical
      characteristic and partial 16S rDNA sequences were used to identify bacteria and
      actinomycetes. Morpholog, growth on various media, and Internal Transcribed
      Spacer (ITS) rDNA sequences homology analysis were performed to identify dominant
      fungi. RESULTS: We isolated seven dominant bacteria strains, seven dominant fungi
      and seven dominant actinomycetes. Dominant bacteria were identified as Leifsonia
      xyli, Arthrobacter chlorophenolicus, Microbacterium flavescens, Sphingomonas sp.,
      Pasteurella sp., Bacillus simplex and Bacillus megaterium. Dominant fungi were
      identified as Cladosporium cladosporioides, Penicillium purpurogenum , Hypocrea
      lixii, Exophiala pisciphila, Penicillium janthinellum, Aspergillus sp. and
      Verticillium dahliae. Dominant actinomycetes were identified as Streptomyces
      violaceoruber, Streptomyces flaveus, Streptomyces panaciterrae, Streptomyces
      achromogenes, Streptomyces pseudogriseolus, Streptomyces cellulosae and
      Streptomyces aureus. CONCLUSION: This study was the first time to isolate and
      identify dominant microorganisms from the rhizosphere of continuous cropping with
      peanut. The type of dominant microorganisms changed obviously after planting
      peanut, although the change was without regularity.

PMID- 21866711
TI  - Home-based music strategies with individuals who have dementia and their family
      caregivers.
AB  - The purpose of this exploratory study was to test a caregiver-administered music
      program with family members who have dementia. The music protocol was designed to
      reduce distress and enhance satisfaction with caregiving, while offering the
      person with dementia the potential to improve mood and psychological state.
      Fourteen elders with dementia and their family caregivers were recruited, and 8
      completed the protocol. Both caregivers and care recipients improved self
      reported relaxation, comfort, and happiness, when mean scores were compared
      between baseline and music conditions. Caregivers showed the most benefit. While
      drop-out was high (6 families dropped), and caregiving satisfaction failed to
      improve over time, caregivers expressed enjoyment in reminiscing and
      participating in musical activities with their loved ones. More direct
      intervention by a music therapist is recommended to improve impact.

PMID- 21866712
TI  - Investigating the dimension of time: findings from a modified grounded theory
      study about clients' experiences and descriptions of temporality or time within
      music therapy.
AB  - Many references to time or temporality are located within music therapy
      literature, however little research has been completed regarding this phenomenon.
      Findings from a modified grounded theory study about clients' experiences and
      descriptions of time within the context of music therapy are presented here. The
      study was informed by the constructivist-interpretive paradigm and a grounded
      descriptive statement finding resulted. A 2-staged research methodology was used,
      comprising a deductive-inductive content analysis of information from the public
      domain, followed by data-mining of information from a minimum of 160 clients and
      analysis of data from at least 43 of these 160 clients. Information regarding
      memory experiences, the duration of music therapy effects, recall and retrieval,
      and experiences of time are identified. Implications for practice are emphasized,
      in particular the following is stressed (a) the importance of time orientation
      and temporal connectedness in relation to identity development, (b) temporal
      strategies within music experience to assist integration, recall, and retrieval
      of information, and (c) the importance of and the elements involved in time
      modification. New explanations for music therapy phenomena are shared, and areas
      for research highlighted. Benefits of using time dynamically to aid therapeutic
      process are proposed, and it is concluded that temporal experience within the
      context of music therapy is important in relation to both practice and research.

PMID- 21866713
TI  - A descriptive study of Myers-Briggs personality types of professional music
      educators and music therapists with comparisons to undergraduate majors.
AB  - The purpose of the current study was to determine personality types and
      demographic characteristics of professional music educators and music therapists.
      The researchers also sought to determine if personality types of professionals
      were consistent with undergraduate majors in those fields and personal
      characteristics as suggested by The Music Education National Conference (MENC)
      and the American Music Therapy Association (AMTA). The research of Steele and
      Young (2008) found strong similarities and some differences between undergraduate
      music education and music therapy students. The possibility that basic types
      extend across the life span may strengthen understanding of job satisfaction,
      stress, burn out and other factors affecting retention. Participants were a
      voluntary convenience sample of 253 music educators (n=110) and music therapists
      (n=143). The highest preference for music educators was Extrovert-Intuition
      Feeling-Judgment (ENFJ) and the highest preference for music therapists was
      Introvert-Intuition-Feeling-Judgment (INFJ). The difference in the collective
      type of each group was their "outlook on life", which was either Extrovert or
      Introvert. However, both groups were the same in their secondary type functions
      of "NFJ". A comparison of findings with the Steele and Young (2008) study
      suggested small changes in personality type over time. Caution must be exercised
      in generalizing findings; however this descriptive investigation may serve as the
      basis for future studies, which should help foster a stable work force in these
      professions.

PMID- 21866714
TI  - A survey of the use of aided augmentative and alternative communication during
      music therapy sessions with persons with autism spectrum disorders.
AB  - Research indicates that as many as 50% of children with autism spectrum disorders
      (ASD) will not develop adequate speech to meet their communication needs (Noens &
      van Berckelaer-Onnes, 2004). Thus, alternate means of communication such as
      Augmentative and Alternative Communication (AAC) are necessary. Though many music
      therapists work with clients with ASD, there is a lack of research regarding
      music therapists' use of aided AAC. This study sought to obtain information from
      music therapists who work with persons with ASD via a survey to answer the
      following questions: (a) how many music therapists are using aided AAC in their
      sessions, (b) how they are using aided AAC, and (c) what type of training they
      have had regarding AAC systems. To assess the research questions, the author
      created an electronic survey. Upon distribution, the survey response rate was
      49.6%. Results indicated that only 14.6% of respondents utilize aided AAC with
      all of their clients who use aided AAC outside of music therapy. The most common
      form of aided input used by music therapists in their sessions with clients with
      ASD is a picture schedule. Only 40% of respondents have additional training in
      aided AAC. Chi square tests revealed significant relationships among many of the
      variables: use of aided AAC and additional training, use and treatment setting,
      literacy promotion and additional training, modeling and additional training,
      referral for AAC systems and length of work with clients with ASD, referral and
      additional training. Results are discussed in relation to current communication
      literature.

PMID- 21866715
TI  - The effect of music video exposure on students' perceived clinical applications
      of popular music in the field of music therapy: a pilot study.
AB  - The purpose of this study was to examine the effect of video exposure on music
      therapy students' perceptions of clinical applications of popular music in the
      field of music therapy. Fifty-one participants were randomly divided into two
      groups and exposed to a popular song in either audio-only or music video format.
      Participants were asked to indicate clinical applications; specifically,
      participants chose: (a) possible population(s), (b) most appropriate
      population(s), (c) possible age range(s), (d) most appropriate age ranges, (e)
      possible goal area(s) and (f) most appropriate goal area. Data for each of these
      categories were compiled and analyzed, with no significant differences found in
      the choices made by the audio-only and video groups. Three items, (a) selection
      of the bereavement population, (b) selection of bereavement as the most
      appropriate population and (c) selection of the age ranges of pre teen/mature
      adult, were additionally selected for further analysis due to their relationship
      to the video content. Analysis results revealed a significant difference between
      the video and audio-only groups for the selection of these specific items, with
      the video group's selections more closely aligned to the video content. Results
      of this pilot study suggest that music video exposure to popular music can impact
      how students choose to implement popular songs in the field of music therapy.

PMID- 21866717
TI  - Wells Capital's Todd Sisson on what investors expect from hospitals.

PMID- 21866716
TI  - The effect of songwriting on knowledge of coping skills and working alliance in
      psychiatric patients: a randomized clinical effectiveness study.
AB  - The purpose of this study was to determine the effects of a songwriting
      intervention on psychiatric patients' knowledge of coping skills and working
      alliance. Participants were randomly assigned to scripted and manualized
      experimental (n=48) or control (n=41) conditions. The experimental condition was
      a group psychoeducational music therapy songwriting session concerning coping
      skills while the control condition was a group psychoeducational session
      concerning coping skills. Both conditions were single-session therapy with
      patients on an acute adult psychiatric unit. Results indicated no significant
      between group differences in measures of knowledge of coping skills, consumer
      working alliance, or perception of enjoyment (p>.05), although the experimental
      condition tended to have slightly higher mean scores than the control group for
      these measures. There was a significant between group difference in measures of
      therapist working alliance (p<.001), with the therapist scoring the experimental
      group higher than the control group. Although the music therapy group had a
      higher mean rate of previous psychiatric hospitalizations, their perception of
      enjoyment scores were still higher than those of the control condition, a finding
      incongruent in the literature. Furthermore, despite the increased number of
      previous hospitalizations, the music therapy condition had higher attendance
      rates than the control condition, thus possibly providing incentives for funding.
      It seems that group songwriting about coping skills can be as effective a
      psychosocial intervention as traditional talk-based psychoeducation to teach
      psychiatric inpatients how to proactively manage their illness. Additionally,
      music therapy can be as effective as talk-based psychoeducation in establishing
      working alliance. Implications for clinical practice, limitations, and
      suggestions for future research are provided.

PMID- 21866718
TI  - The oracle within MedPAC.

PMID- 21866719
TI  - ICD-10 obligations and opportunities.
AB  - As the Oct. 1, 2013, ICD-10 compliance date approaches, hospitals should be
      taking five key action steps: Establish a project management team. Create an
      implementation plan. Produce and project a timeline. Prepare a gap analysis for
      each department or system. Calculate and prepare for impact on the revenue cycle.

PMID- 21866720
TI  - Cloud computing can simplify HIT infrastructure management.
AB  - Software as a Service (SaaS), built on cloud computing technology, is emerging as
      the forerunner in IT infrastructure because it helps healthcare providers reduce
      capital investments. Cloud computing leads to predictable, monthly, fixed
      operating expenses for hospital IT staff. Outsourced cloud computing facilities
      are state-of-the-art data centers boasting some of the most sophisticated
      networking equipment on the market. The SaaS model helps hospitals safeguard
      against technology obsolescence, minimizes maintenance requirements, and
      simplifies management.

PMID- 21866721
TI  - Highlights from HFMA's 2011 Compensation Survey.

PMID- 21866722
TI  - What value-based purchasing means to your hospital.
AB  - Under the new Value-Based Purchasing program, hospitals will receive incentive
      payments based on how well they perform on 12 clinical process measures and nine
      patient experience measures or on how much their performance improves relative to
      a baseline performance period. It is likely that as many hospitals will be
      penalized with payment reductions under the program as will benefit from payment
      increases from the incentive payments. It can be argued that the true
      significance of the program is not so much in the incentive payments as it is in
      the measurement tools it provides.

PMID- 21866723
TI  - Dennis Dahlen: implementing an intense integration strategy.

PMID- 21866724
TI  - The 4 phases of quality maturity.
AB  - Evaluating a hospital's quality performance involves several key considerations:
      What drives the hospital's quality-of-care scores, and what are the underlying
      drivers of its outcomes and patient satisfaction? How does the hospital's quality
      and cost of care compare with those of its peers? Does the organization have a
      road map for predictable quality improvement? How do quality improvement
      initiatives affect financial performance? Does the chief quality officer (CQO)
      have a "seat at the table" in boardroom meetings? Does the strategic plan include
      quality goals? Does the hospital possess analytical tools to measure and
      understand quality of care with a holistic view and in financial context?

PMID- 21866725
TI  - Clinical documentation improvement: focus on quality.
AB  - Accurate clinical documentation is necessary for healthcare organizations to
      achieve quality improvement and accurate payment. Physician buy-in is essential
      to a successful clinical documentation improvement program. The program should
      not focus on revenue enhancement or a particular tool, but should encourage
      critical thinking by physicians.

PMID- 21866726
TI  - Accountable care: are you ready?
AB  - Ten steps are required to develop an ACO that can thrive in the emerging
      healthcare environment: Assess readiness for accountable care. Assemble the right
      project team. Create a legal and organizational framework for an ACO. Form the
      right leadership team. Strategically align human capital. Ensure minimal
      operational requirements are met. Assess all dimensions of financial readiness.
      Integrate IT to the point of "meaningful use." Strengthen partner relationships
      and business networks. Engage the community as an ally.

PMID- 21866727
TI  - The case for evidence-based human capital management.
AB  - Healthcare finance leaders should adopt seven strategies to leverage their
      organizations' workforces more efficiently: Commit to developing a formal
      workforce planning program. Incorporate values in appraisals of staff work
      requirements and competencies. Appraise individual performance. Assess future
      work requirements. Assess future potential. Close the developmental gap. Evaluate
      the success of the program.

PMID- 21866728
TI  - Hospital case management and progression of care.
AB  - Progression of care refers to a three-pronged approach to managing the
      complexities of the fragmented care delivery that is commonplace in U.S.
      healthcare systems. Under this approach: Case managers-freed from the need to
      perform routine chart reviews-work with the physicians to manage progression of
      care Utilization review/clinical documentation specialists ensure complete and
      accurate documentation to support acute level of care Coordinators are dedicated
      exclusively to finding and arranging post-acute services

PMID- 21866729
TI  - Connecting cost and quality through automated discharge instructions.
AB  - By using 140 sets of automated discharge instructions, Department of Veterans
      Affairs Medical Center at Portland, Ore., cut its 14-day readmission rate to 1.5
      for every 1,000 outpatient procedures. Providers are prompted to document: Dosage
      directions for any medications to be taken upon discharge The date when it is
      safe to resume any medications taken routinely Pain medications received during
      the procedure Dates of follow-up appointments

PMID- 21866731
TI  - The tax support of independent community hospitals.

PMID- 21866730
TI  - How should the medical staff and hospital be aligned in a post-reform market?

PMID- 21866732
TI  - Discharges decreasing for most hospitals.

PMID- 21866733
TI  - Effect of vestibular neuritis on postural control using wavelets and fractal
      analysis.
AB  - OBJECTIVE: What is the status of postural control a few months after an attack of
      vestibular neuritis (VN)? Using dynamic posturography and stabilometric signal
      treatment with wavelets and fractal analysis, we tried to answer this question by
      isolating the pathological postural parameters of VN. MATERIAL AND METHOD: The
      study involved a group of 15 patients (GP) who suffered from VN and were compared
      to a group of control subjects (GC). Both groups underwent videonystagmography
      (VNG), dynamic posturography (PDY), and assessment using symptomatic scales (ES).
      RESULTS: GP and GC were comparable in terms of age mean, sex-ratio, average
      height and weight. The differences between GP and GC were the following
      videonystagmography criteria: Spontaneous nystagmus (NS) (P= 0.005), head shaking
      test (HST) (p= 0.001), vibratory test (TVO) (p= 0.009). There were also
      differences in the symptomatic scales scores for the vertigo symptom scale (VSS)
      (p= 0.011), the dizziness handicap inventory (DHI) (p= 0.001), and the short form
      36 (SF36) (p= 0.01). All the 84 new parameters of both GP and GC differ. This
      difference was significant (p< 0.05) in 16 cases (19%), and highly significant
      (p< 0.01) in 11 other cases (13%). The condition ("unsteady platforms" was the
      greatest determinant in both groups while the (closed eyess and (HST> conditions
      were found to be non-discriminating. CONCLUSION: Vestibular neuritis affects new
      stabilometric parameters. These parameters are more adapted to the present setup
      compared to previous parameters which are used to analyse non-periodic
      oscillations of posture. They are important in follow-up and rehabilitation of
      patients.

PMID- 21866734
TI  - Hypersensitivity to inhalants and food in balance disturbances.
AB  - INTRODUCTION: The prevalence of allergy in patients with Meniere's disease was
      established as approximately 41.6% for inhalants and 26.6% for food. These are
      elevated values in relation to the prevalence of allergy in the general
      population, which varies from 9% to 30% for inhalants (in Brazil) and from 1% to
      3% for food. OBJECTIVES: To evaluate the prevalence of type I hypersensitivity
      reactions to inhalants and food in the patients of the Neurotology Sector of the
      'Hospital das Clinicas' of the University of Sao Paulo Medical School and to
      describe vestibular symptoms of these patients. METHOD: Seventy-five patients
      with imbalance due to peripheral origin were evaluated by a questionnaire for the
      clinical characterization of the cochleo-vestibular symptoms and underwent the
      prick test for 13 inhalants and 5 food stuffs. RESULTS: Twenty-five (33.3%)
      patients presented positive prick tests and, at least, one food allergen. Four
      patients presented positive prick tests without allergy symptoms. The prevalence
      of the complaint of rotatory dizziness was similar among the patients with
      positive and negative prick tests. CONCLUSION: The prevalence of Type I
      hypersensitivity reactions to inhalants and food in the population evaluated was
      greater than in the general population. The vestibular symptoms did not differ
      among the patients with either positive or negative prick tests. However, a
      larger sample size should be obtained for the data to be more reliable.

PMID- 21866735
TI  - [Facial nerve monitoring in the parotidectomy].
AB  - INTRODUCTION: Facial palsy (FP) is a feared complication of parotidectomy. Facial
      nerve monitoring (FNM) has been poorly evaluated since it was created at the
      beginning of the 90's. The authors described a retrospective series and discussed
      it reviewing the literature data. SUBJECTS AND METHOD: From January 2002 to
      January 2009, 75 parotidectomies were performed in 72 patients (34 males, 38
      females), without FNM in 28 cases (group 1) and with FNM in 47 cases (group 2).
      RESULTS: In group 1, 9 FP were noted, 5 were transient and 4 were definitive. In
      group 2, 12 FP were noted, 9 were transient and 3 were definitive. Both one month
      and six months after parotidectomy, the FP rate was significatively higher in
      group 1 than in group 2 for the reoperations. CONCLUSIONS: Facial nerve
      monitoring is an adjunctive method available to a surgeon during parotid surgery
      to assist with the functional preservation of the facial nerve. It did not allow
      to improve the facial prognosis in benign tumours removal but it improved the
      facial prognosis in reoperations. Its interest should be tested for malignant
      tumour removal.

PMID- 21866736
TI  - [Comparison between external radiotherapy and laser microsurgery for the
      treatment of TisT1N0 glottic carcinoma: Clinical modelling and cost-minimization
      study from the French national health insurance payer's point of view].
AB  - OBJECTIVES: The excellent effectiveness of both treatment modalities
      (radiotherapy, endoscopic laser surgery) for early glottic carcinoma (Tis, TlaN0)
      is similar (carcinologic, functional and QoL results). This is part of an
      evidence-based medicine policy, which is to choose the cheapest of various
      treatment modalities known as equally effective and equally morbid. Is analytical
      economic approach useful and efficient to guide decision making? The aim of this
      study is to perform a costminimization analysis using an objective clinical
      modeling. MATERIAL AND METHODS: For each modality, probabilities of various
      events were recorded from review of literature. Only local recurrences which
      constitute the major end-point affecting survival were considered. French
      national Health insurance's point of view (as the payer's point of view), with a
      100% case-mix based payment system was used. Results of cost-minimization between
      laser endoscopic surgery and external radiation therapy are: Global Cost of laser
      endoscopic surgery is about 2613.01 euro. Without (90% of cases) and with
      recurrence it is about 1700.36 euro and 10826.87 euro respectively. Global Cost
      of external radiation therapy is about 4490.88 euro. Without (90% of cases) and
      with recurrence it is about 3578.23 euro and 12704.74 euro respectively.
      CONCLUSION: Cordectomy by CO2 laser seems to be an efficient cost-effective
      alternative to radiotherapy for early glottic carcinoma management from the
      French national Health insurance perspective.

PMID- 21866737
TI  - Revascularized free scapular flaps in mandibular reconstruction. Report of 93
      cases (April 1997 - October 2009).
AB  - OBJECTIVE: The aim of the present article is to demonstrate the relevance of
      revascularized free scapular flap in mandibular reconstruction in oncological
      cervicofacial salvage surgery. We will discuss the advantages and the
      disadvantages, indications and contraindications, together with possible
      complications and sequelae for this type of surgical flap. MATERIAL AND METHODS:
      Retrospective study of 93 revascularized free scapular flaps used to reconstruct
      segmental substance defects in the mandible from April 1997 to October 2009 (in
      91 patients). All patients benefited from 10 months to 12 years follow-up
      surgical and functional results. Functional assessment following anatomic site
      restoration focused on the quality of feeding and deglutition. RESULTS: The
      anatomical success rate was 94.63% (5 complete necroses out of 93 flaps). Results
      were considered to be good (normal or close to normal function for feeding and
      deglutition) in the majority of patients (83% at 6 months, 91% at 18 months). On
      the donor site: Functional sequelae were moderate when post-operative reeducation
      was correctly performed. CONCLUSION: Vascularized free scapular flap bone graft
      is very interesting for the reconstruction of mandibular discontinuity, composite
      (soft tissue and cutaneous resection) or exclusively osseous defects (not in
      excess of 13 cm), secondary to oncologic or osteoradionecrotic resections.

PMID- 21866738
TI  - Surgical management of maxillary sinonasal inverted papilloma.
AB  - OBJECTIVE: The extent of the surgery required when sinonasal inverted papilloma
      (IP) originates in the maxillary sinus is still the subject of debate. The
      principal aim of the study was to evaluate the efficacy of exclusive endoscopic
      removal or when combined with a limited vestibular anterior antrostomy of the
      maxillary IP. METHODS: A retrospective analysis was carried out of 64 patients
      with IP treated in our university tertiary referral center from 1993-2007.
      Endoscopic removal of the IP was done for all patients, either exclusively or
      combined with an open approach. All patients were followed up for more than 1
      year and the local control rate has been compared between patients with maxillary
      IP and others, and with both approaches. RESULTS: The overall recurrence rate was
      14% (9/64), for a mean follow up of 48 months (12-120 months). Twenty-three
      patients (23/64) had maxillary IP. Ten of them had endoscopic resection alone, 13
      had a combined approach (1 with lateral rhinotomy). There were 4 recurrences
      (17%) three of which had had endoscopic surgery alone. We did not perform a
      medial maxillectomy in the first instance. There were no cases of epiphora or
      atrophic rhinitis. conclusion: We showed that the combined method (endoscopic
      assisted by a minimal vestibular approach) was an efficient and safe method to
      treat maxillary sinus IP. This approach could preserve the lacrimal duct and the
      inferior turbinate when these structures were not involved, even when there was a
      large maxillary sinus extension of the disease.

PMID- 21866739
TI  - Inferior turbinate hypertrophy radiofrequency management for children with cystic
      fibrosis.
AB  - OBJECTIVE: To evaluate, using radiofrequency techniques, the relevance and
      effectiveness of treatment of inferior turbinate hypertrophy in children with
      cystic fibrosis. MATERIALS AND METHODS: A study of patients with cystic fibrosis
      with hypertrophy of inferior turbinate who were being treated at Lisieux Hospital
      In-Patient Paediatric and ENT- Head and Neck Surgery Department. 41 patients were
      included in the study and followed over 2 years. We analyzed the postoperative
      phase and the effectiveness of treatment, through clinical and radiological
      examination. RESULTS: A clinical improvement of symptoms is observable from the
      third month after surgery in 100% of cases. However, we noted a loss in the
      effectiveness of radiofrequency on the turbinate tissue one year following
      operation, which worsens with time. However, the postoperative results remain
      satisfactory at 1 year and 2 years. CONCLUSION: Radiofrequency is, in our
      opinion, the treatment of choice for inferior turbinate hypertrophy in children
      with cystic fibrosis. It combines a simple and low-risk effect with effective
      preservative treatment. However, the benefits of radiofrequency fade with time.
      Nonetheless, this technique yields postoperative results that remain satisfactory
      beyond 2 years. It is often useful to consider a new session after this date.

PMID- 21866740
TI  - [Arachnoid granulations of the posterior temporal bone wall: report of two
      cases].
AB  - Arachnoid granulations play a role in CSF drainage. They are primarily located
      adjacent to cerebral venous sinuses. They may arise on a bony surface causing
      progressive bony erosion. We report two cases of arachnoid granulations eroding
      the posterior wall of the temporal bone. The aim of this paper was to illustrate
      the clinical presentation, and the imaging findings of arachnoid granulation of
      the posterior wall of the temporal bone. They remain asymptomatic in most cases,
      but they might cause a communication between the subarachnoid space and mastoid
      air cells, increasing the risk of bacterial meningitis, subdural empyema, and
      other intracranial infections. Differential diagnoses are also described,
      including endolymphatic sac tumours.

PMID- 21866741
TI  - Acute infectious complications in stapes surgery.
AB  - OBJECTIVES: The purpose of this report is to describe the symptoms, management
      and outcomes of three patients who developed infection related complications
      within one month after stapes surgery. A literature review of early post
      operative complications following stapes surgery will also be presented. SETTING:
      Private tertiary medical center. PATIENTS: This is a report of three patients
      diagnosed with otosclerosis who were operated by the senior author in a span of
      16 years from 1993 to 2009. RESULTS: The first patient was a young man who
      experienced complications brought about by recurrent upper respiratory tract
      infection and Eustachian tube dysfunction due to enlarged palatine tonsils. The
      second patient was a woman who developed acute suppurative otitis media after
      stapes surgery of the left ear. When she underwent stapes surgery for the right
      ear, she had an upper respiratory tract infection two days after the procedure.
      The third patient was a known diabetic female who developed otitis media and had
      a prolonged recovery despite being managed by an endocrinologist prior to stapes
      surgery. Two patients fully recovered and hearing eventually improved on the
      operated side while one patient did not benefit from stapes surgery. CONCLUSION:
      Complications in stapes surgery are very rare in the past and at present.
      However, complications still happen. Effective, timely medical treatment,
      vigilance and proper follow-up advice always lead to favourable outcomes.

PMID- 21866742
TI  - [Cranial fasciitis of childhood].
AB  - OBJECTIVE: To describe the clinical and pathological features of cranial
      fasciitis of childhood, and to review and compare this case with those of
      international literature. METHODS: We report a case of cranial fasciitis of
      childhood located on the face of a 13-month-old boy. A complete review was
      performed from the database "Pub Med", looking for the key words "head and neck
      inflammatory myofibroblastic tumour", "nodular fasciitis", "cranial fasciitis of
      childhood". RESULTS: Cranial fasciitis is benign rapidly growing fibroblastic
      tumour, belonging to the group of nodular fasciitis, and has a predilection for
      the head and neck region of young children. This tumour is highly cellular and
      often show striking erosion of bone often misdiagnosed as a sarcoma. Surgery with
      adequate resection margin is the best treatment. There is no tendency for local
      recurrence. CONCLUSION: Positive pathological diagnosis of cranial fasciitis is
      uncommon and may be difficult.

PMID- 21866743
TI  - [Eagle syndrom: A case report].
AB  - INTRODUCTION: The Eagle syndrome is a rare entity characterized by a hypertrophy
      of the styloid process responsible for clinical signs in connection with
      compression of the vasculonervous structures of vicinity. CASE REPORT: Female 40
      years old who complained for 7 years about intense right temporo-parietal
      headache, associated with ocular pains, otalgia, tinnitus and swallowing
      problems. These symptoms were unilateral. The only notable antecedent was an
      extraction of the wisdom teeth of the lower arc 10 years before. CONCLUSION: The
      Eagle syndrome is an unusual syndrome ignored by the majority of the clinicians.
      The simple palpation of the oropharyngeal walls (tonsils) makes it possible to
      evoke the diagnosis. This suspicion will be confirmed by Xrays. The surgery
      presents few risks and the patient is released of symptoms very quickly.

PMID- 21866744
TI  - [Acinic cell carcinoma in an ectopic salivary gland].
AB  - On the occasion of the coverage of a cervical tumefaction in a child, which led
      to the diagnosis of acinic cell carcinoma of ectopic salivary gland, the authors
      conducted a literature review of this tumour. If it is well known to pathologists
      when it is developed in the major or accessories salivary glands, its location
      within heterotopy of salivary tissue is much rarer. From a histological point of
      view it is difficult to distinguish, if primitive location, the occurrence of the
      tumour in an ectopic salivary gland, its occurrence in intra-node heterotopic
      salivary tissue. This distinction between glandular ectopia and intra-node
      heterotopia remains purely theoretical, and does not affect the therapeutic
      decision. This one remains empirical and discussed on a case-by-case basis for a
      malignant tumour that is exceptional in this location and at that age.

PMID- 21866745
TI  - [Recurrent ameloblastoma on a rib graft after 33 years (a case report and review
      of the literature)].
AB  - INTRODUCTION: The recurrence of an ameloblastoma is generally due to insufficient
      margins of resection or to the aggressiveness of the tumour which is regarded as
      locally malignant. Recurrencies on autologus osseous graft are rare in the
      literature. We report the case of a recurrent ameloblastoma on autologus rib
      graft which occurred 33 years after the surgery. OBSERVATION: A 59 year old man,
      underwent at the age of 26 years a tumoral removal of a left mandibular cyst with
      reconstruction by costal graft. The histopathologic diagnosis was an
      ameloblastoma with healthy limits and without invasion of the soft tissues. He
      consulted recently for a tumour located at the left side of the symphysis and
      presenting an endo-oral component bending at the level of the floor of the mouth.
      The CTscan objectified a cystic hypodensity well defined inside the rib graft.
      The patient underwent a surgery performed by a mixed approach (endo-oral and
      cervical). The tumour was removed with macroscopically healthy margins.
      CONCLUSION: The pathogenesis of the recurrence of an ameloblastoma on autologus
      osseous graft is still not well understood. Thus, it is recommended to get
      healthy margins in case of en bloc resection requiring to make the limits of the
      resection at least at one centimeter from the tumour. A very longterm follow-up
      clinical and radiological is also mandatory.

PMID- 21866746
TI  - A remnant tooth in an edentulous patient.
AB  - OBJECTIVES: We describe a case of an unusual remnant tooth located in the
      paranasal sinus in a head and neck cancer patient. CASE REPORT: A 72-year patient
      with a history of T3N2aM0 oropharyngeal cancer treated with chemoradiation came
      for systematic post-therapeutic multidetector-CT reformation (MDCT) examination.
      MDCT scan multi planar reformation revealed a well-limited high-density mass in
      his maxillary sinus, which proved to be a remnant molar tooth. Physical
      examination and CT imaging were performed at 26 months. Local malignancy, fungal
      ball and persistent oroantral fistula were ruled out. CONCLUSION: The physio
      pathogenesis of oroantral fistula (OAF) and causes of intra sinusal tooth as well
      as therapy are discussed in this article.

PMID- 21866747
TI  - Cholesterol granuloma of the maxillary sinus.
AB  - INTRODUCTION: Cholesterol granuloma (CG) can be found in several areas of the
      body. Maxillary sinus localization is considered rare. CASE REPORT: A 37-year-old
      male presented with acute febrile sinusitis. Nasal endoscopy showed a nasal polyp
      at the middle meatus. Computed Tomography (CT scan) of the sinus showed complete
      opacity of the right maxillary sinus without calcification and partial
      opacification of frontal and ethmoidal sinuses. Functional endoscopic sinus
      approach was performed. Marsupialization of the cyst which a brownish fluid,
      which evoked the diagnosis of cholesterol granuloma. CONCLUSION: The definite
      diagnosis is made by histology, although intra-operative finding could be
      suggestive. Complete excision is achievable by endoscopic approach.

PMID- 21866748
TI  - Sinonasal hemangiopericytoma.
AB  - Hemangiopericytoma (HPC) is a rare entity that is found in only 1% of vascular
      tumours. Only 5% of HPC are localized in the nasal cavity or paranasal sinuses.
      The exact incidence is not stated in the literature. CASE REPORT: A case of a 76
      year-old female patient is presented. As she suffered from stroke a cranial CT
      was performed and the tumour of the paranasal sinuses was diagnosed incidentally.
      The patient had a history of paranasal sinus surgery under local anaesthesia
      twenty years ago. The former histological diagnosis was stated as "angiofibroma
      with signs of proliferation ". The histopathologic diagnosis after endonasal
      sinus surgery was primarily a neoplasia with spindle-shaped cell formation. Just
      additional immunocytochemistry revealed the finding of primitive mesenchymal
      cells. This confirmed the diagnosis of a hemangiopericytoma. The two years follow
      up showed no signs and symptoms of recurrent tumour on endoscopic examination and
      CT scans. CONCLUSION: Hemangiopericytoma is a rare endonasal or sinonasal tumour.
      Occasionally histological diagnosis is difficult. Its characteristics are marked
      cellularity, vascularity and a dense net of reticular fibres. The entity shows a
      considerable tendency to recurrence, malignant transformation and metastasizing.
      After complete sinonasal surgery a regular short term follow up is advisable.

PMID- 21866749
TI  - [Sphenoid arachnoidocele: report of one case].
AB  - OBJECTIVES: To define a diagnostic strategy of a sphenoid sinus lesion and the
      management of CSF fluid leak in the case of a sphenoid arachnoidocele. MATERIALS
      AND METHODS: A 70-year-old woman exhibited a sphenoidal sinus opacity which was
      discovered on the assessment of chronic headaches. It was labelled sphenoid
      mucocele. A cerebrospinal fluid leak occurred when the marsupialization was made.
      After an assessment of additional imaging (MRI, CTscan), the diagnosis of
      sphenoid arachnoidocele was retained. RESULTS: The leak was repaired by navigated
      endoscopic endonasal surgery. We used a multilayer reconstructive technique with
      autologous materials (abdominal fat, fascia of muscle, middle turbinate) and
      fibrin glue. With a decline of eighteen months no rhinorrhea was noted.
      CONCLUSION: Sphenoid arachnoidocele is a rare disease. This case shows that it's
      essential to know the differential diagnosis sphenoid sinus lesions and how to
      repair an osteomeningeal leak.

PMID- 21866750
TI  - [Pneumatization (concha bullosa) of the inferior turbinate: cas report and
      literature review].
AB  - OBJECTIVE: We report a case of concha bullosa of the inferior turbinate. MATERIAL
      AND METHOD: A 58 year-old man, consulted for a per annual bilateral nasal
      obstruction with normal endoscopic examination. RESULT: The CT scan (sagittal and
      axial sections) of the face had shown a concha bullosa of the inferior turbinate.
      CONCLUSION: The concha bullosa of inferior turbinate is uncommon entity and may
      be to reconnize after chronic nasal or sinusal dysfunction. The concha bullosa
      can be united or bilateral, isolated or combined with other turbinates anomalies.
      This unusual pathology deserves to be reported. We found 25 cases published in
      the literature. A discussion around this entity is made after reporting this
      observation.

PMID- 21866751
TI  - Enhanced reduction of excess sludge and nutrient removal in a pilot-scale A2O-MBR
      TAD system.
AB  - In this study, a pilot scale anaerobic-anoxic-oxic (A2O) process with submerged
      membrane (MBR) in the oxic tank was coupled with thermophilic aerobic digestion
      (TAD) reactor and was operated for longer than 600 days to treat real domestic
      wastewater. Regardless of the varying conditions of the system, the A2O-MBR-TAD
      process removed MLSS, TCOD, BOD, TN, TP, and E. coli about 99%, 96%, 96%, 70%,
      83%, and 99%, respectively. The additional TP removal of the system was due to
      the precipitating agent directly added in the oxic reactor, without which TP
      removal was about 56%. In the TAD reactor, receiving MLSS from the oxic tank
      (MBR), about 25% of TSS and VSS were solubilized during 2 days of retention. The
      effluent of the TAD reactor was recycled into the anoxic tank of A2O-MBR to
      provide organic carbon for denitrification and cryptic growth. By controlling the
      flowrate of wasting stream from the MBR, sludge production decreased to almost
      zero. From these results, it was concluded that the A2O-MBR-TAD process could be
      a reliable option for excellent effluent quality and near zero-sludge production.

PMID- 21866752
TI  - The innovative osmotic membrane bioreactor (OMBR) for reuse of wastewater.
AB  - An innovative osmotic membrane bioreactor (OMBR) is currently under development
      for the reclamation of wastewater, which combines activated sludge treatment and
      forward osmosis (FO) membrane separation with a RO post-treatment. The research
      focus is FO membrane fouling and performance using different activated sludge
      investigated both at laboratory scale (membrane area of 112cm2) and at on-site
      bench scale (flat sheet membrane area of 0.1 m2). FO performance on laboratory
      scale (i) increased with temperature due to a decrease in viscosity and (ii) was
      independent of the type of activated sludge. Draw solution leakage increased with
      temperature and varied for different activated sludge. FO performance on bench
      scale (i) increased with osmotic driving force, (ii) depended on the membrane
      orientation due to internal concentration polarization and (iii) was invariant to
      feed flow decrease and air injection at the feed and draw side. Draw solution
      leakage could not be evaluated on bench-scale due to experimental limitation.
      Membrane fouling was not found on laboratory scale and bench-scale, however,
      partially reversible fouling was found on laboratory scale for FO membranes
      facing the draw solution. Economic assessment indicated a minimum flux of 15L.m-2
      h-1 at 0.5M NaCl for OMBR-RO to be cost effective, depending on the FO membrane
      price.

PMID- 21866753
TI  - Straw preservation effects of Arundo donax L. on its allelopathic activity to
      toxic and bloom-forming Microcystis aeruginosa.
AB  - In this study, straw preservation effects of Arundo donax L. on its allelopathic
      activity to toxic and bloom-forming Microcystis aeruginosa were investigated. The
      aquatic extracts of fresh straw significantly inhibited the growth of M.
      aeruginosa. After 7 d of cultivation, the percentage inhibitions (Pls) of all
      treated groups were above 60% and the maximum almost reached 100%. However, when
      the straw was used after two-month preservation, its allelopathic activities
      decreased significantly with all PIs lower than 60%. To unclose the substance
      differences between fresh and long-time preserved straws, the contents of
      dissolved organic carbon (DOC) and ultraviolet-visible and fluorescence
      characteristics were analyzed. The results show that long-time preserved straw
      had lower DOC and UV254 values, weaker fluorescence intensities, and fluorescent
      substance loss. Further, the allelopathic fractions were isolated from the
      aquatic extracts of the straws by solvent extraction. The potential
      allelochemicals were analyzed by gas chromatography-mass spectrometry (GC-MS).
      The strong antialgal fractions of both fresh and long-time preserved straws were
      found to have various potential allelochemicals, including esters, ketones,
      alkaloids and phenolic acids. Their number was decreased from 21 to 9 after two
      month preservation. The characteristics analysis of potential allelochemicals
      hinted that fresh A. donax might have more highly-effective allelochemicals than
      long-time preserved one.

PMID- 21866754
TI  - Study of water-table behaviour for the Indian Punjab using GIS.
AB  - The state of Punjab (India) has witnessed a spectacular increase in agricultural
      production in the last few decades. This has been possible due to high use of
      fertilizers, good quality seeds and increased use of water resources. This
      increased demand of water resources has resulted in extensive use of groundwater
      in the central districts of the state and surface water (canals) in South-West
      Punjab, where groundwater is of poor quality in general. The state has been
      facing the twin problem of water table decline/rise in different parts. Efficient
      management relies on comprehensive database and regular monitoring of the
      resources. GIS is one of the important tools for integrating and analyzing
      spatial information from different sources or disciplines. It helps to integrate,
      analyze and represent spatial information and database of any resource, which
      could be easily used for planning of resource development, environmental
      protection and scientific researches and investigations. Geographical Information
      Systems (GIS) have been used for a variety of groundwater studies. Groundwater
      level change maps are useful in determining areas of greatest changes in storage
      in the regional systems. In this study, an attempt has been made to assess the
      long term groundwater behaviour of the state using GIS to visually and spatially
      analyze water level data obtained from the state and central agencies. The data
      was analysed for 0-3 m, 3-10 m, 10-20 m and beyond 20 m. The study revealed that
      per cent area with water table depth > 10 m was 20% in 1998 and has increased to
      58% by 2006 which is critical limit for shifting from centrifugal pump to
      submersible pump.

PMID- 21866755
TI  - H2 consumption by anaerobic non-methanogenic mixed cultures.
AB  - The impact of H2 consumption, by homoacetogens, on the overall hydrogen yield in
      mixed culture fermentation is the focus of this study. Batch reactors were used
      to test the ability of anaerobic digested sludge, heat treated to eliminate
      methanogens, to produce and consume molecular hydrogen. The measured average
      hydrogen production rate from 4.2 g glucose/L was 44 +/- 4 mmol H2/L sludge . d,
      while the H2 consumption rate varied much more, in the range from 4 to 62 mmol
      H2/L sludge . d. Hydrogen consumption rate depends on acetic acid concentration,
      headspace H2 partial pressure and mass transfer rates. Different but relatively
      long lag-phases for hydrogen consumption were observed. It is concluded that
      homoacetogenesis can have a significant negative effect on bio-H2 production by
      mixed cultures, limiting the possibilities for sustainable solutions.

PMID- 21866756
TI  - Is the whole the sum of its parts? Agent-based modelling of wastewater treatment
      systems.
AB  - Agent-based models (ABMS) simulate individual units within a system, such as the
      bacteria in a biological wastewater treatment system. This paper outlines past,
      current and potential future applications of ABMs to wastewater treatment. ABMs
      track heterogeneities within microbial populations, and this has been
      demonstrated to yield different predictions of bulk behaviors than the
      conventional, "lumped" approaches for enhanced biological phosphorus removal
      (EBPR) completely mixed reactors systems. Current work included the application
      of the ABM approach to bacterial adaptation/evolution, using the model system of
      individual EBPR bacteria that are allowed to evolve a kinetic parameter (maximum
      glycogen storage) in a competitive environment. The ABM approach was successfully
      implemented to a simple anaerobic-aerobic system and it was found the differing
      initial states converged to the same optimal solution under uncertain hydraulic
      residence times associated with completely mixed hydraulics. In another study, an
      ABM was developed and applied to simulate the heterogeneity in intracellular
      polymer storage compounds, including polyphosphate (PP), in functional microbial
      populations in enhanced biological phosphorus removal (EBPR) process. The
      simulation results were compared to the experimental measurements of single-cell
      abundance of PP in polyphosphate accumulating organisms (PAOs), performed using
      Raman microscopy. The model-predicted heterogeneity was generally consistent with
      observations, and it was used to investigate the relative contribution of
      external (different life histories) and internal (biological) mechanisms leading
      to heterogeneity. In the future, ABMs could be combined with computational fluid
      dynamics (CFD) models to understand incomplete mixing, more intracellular states
      and mechanisms can be incorporated, and additional experimental verification is
      needed.

PMID- 21866757
TI  - Tolerance of the antibiotic tylosin on treatment performance of an up-flow
      anaerobic stage reactor (UASR).
AB  - Tylosin has been considered inhibiting COD removal in anaerobic digestion. In
      this study it is proven that this is not always the case. Accordingly, elevated
      concentrations of Tylosin (100-800mgL-1) could be tolerated by the anaerobic
      system. The influence of Tylosin concentrations on an up-flow anaerobic stage
      reactor (UASR) was assessed using additions of Tylosin phosphate concentrate.
      Results showed high efficiency for COD removal (average 93%) when Tylosin was
      present at concentrations ranging from 0 to 400 mg L-1. However, at Tylosin
      concentrations of 600 and 800 mg L-1 treatment efficiency declined to 85% and 75%
      removal respectively. The impact of Tylosin concentrations on archaeal activity
      were investigated and the analysis revealed that archaeal cells dominated the
      reactor, confirming that there was no detectable inhibition of the methanogens at
      Tylosin levels between 100 and 400mg L-1. Nevertheless, the investigation showed
      a slight reduction in the number of methanogens at Tylosin levels of 600 and 800
      mg L-1. These results demonstrated that the methanogens were well adapted to
      Tylosin. It would not be expected that the process performance of the UASR would
      be affected, not even at a level well in excess of those appearing in real
      wastewater from a Tylosin production site.

PMID- 21866758
TI  - Biosorption of lead (II) and cadmium (II) using Escherichia coli genetically
      engineered with mice metallothionein I.
AB  - Contamination caused by heavy metals in wastewater has a high potential of risk
      because they easily penetrate in to the trofic chain accumulating as
      organometallic compounds. In this work, the expression of mice metallothionein in
      E. coli (pMt-Thio) was examined as a strategy to enhance metal biosorption
      efficiency of bacterial biosorbents for Pb(II) and Cd(II) ions. The results
      showed that pMt-Thio led to significant increase in overall biosorption capacity,
      especially for biosorption of Pb. Isotherms and kinetic of biosorption were
      evaluated in this designed system. The influence of metal concentration in
      solution is discussed in terms of Langmuir and Freundlich isotherm and constants.
      The Langmuir model was found to correlate better with the experiment data. The
      biomass showed maximum capacities according to Langmuir adsorption model of 28.14
      mgPb/gpMt-Thio and 24.27 mgCd/gpMt-Thio. The study proved that pMt-Thio is a
      suitable material for the removal of the heavy metal ions studied from aqueous
      solutions, achieving removal efficiencies higher than 90% for Pb(II) and higher
      than 40% for Cd(II), and could be considered as a potential material for treating
      effluent polluted with Cd(II) and Pb(II) ions.

PMID- 21866759
TI  - The Rhizopur process ten years on: a green solution for sewage treatment in small
      communities.
AB  - Ten years ago the Rhizopur process was conceived in order to treat sewage from
      small towns. Since 1999 when the first Rhizopuru plant was commissioned, the
      number of facilities has been growing steadily and today there are more than
      fifty Rhizopur'" facilities in France. This process combines three existing
      technologies, i.e. biofilm, infiltration/percolation and mineralisation in
      constructed wetlands, to conduct both wastewater and sludge treatment in a very
      cost-effective fashion. A trickling filter or a rotating biological contactor is
      combined with constructed wetlands to produce a high quality effluent, i.e. BOD5
      <20 mg/I, COD<100 mg/I and TSS < 30 mg/I, and to achieve high removal
      efficiencies, i.e. BOD5 removal >90%, COD removal >80% and TSS removal >90%.
      Nitrification can also be achieved by increasing the size of the trickling
      filter. Part of the success of this process has been its modularity and
      compactness that have resulted in its easiness for extension, as well as its
      capacity to blend with the environment. The characteristics of this process make
      of it an appropriate solution for sewage treatment in the developing countries.
      The objective of this work is to give an overview of the performance and features
      of this process according to the operational experience gained during the last 10
      years.

PMID- 21866760
TI  - Immobilization of horseradish peroxidase on silane-modified ceramics and their
      properties: potential for oily wastewater treatment.
AB  - Horseradish peroxidase (HRP) is proved being effective in eliminating oil from
      aqueous solutions, but the elimination is expensive because free HRP can not be
      reused. In present work, HRP was successfully immobilized on cordierite porous
      ceramics support with a novel method of N-beta-aminoethyl-gamma-aminopropyl
      trimethoxysilane modification and glutaraldehyde activation. Under the optimized
      immobilized conditions, the actual immobilized HRP was 1.16 mg/g support, the
      activity of the immobilized HRP could reach as high as 1379.4 U/g support.
      Experiment results showed that the properties of storage stability, acid-base
      stability and the tolerance to the pH fluctuation of the immobilized HRP were
      better than those of the free HRP. The operation stability of the immobilized HRP
      was also good. The immobilized HRP is suitable for the oily wastewater treatment
      because of its reusability proved in this work.

PMID- 21866761
TI  - Phosphorus removal by apatite in horizontal flow constructed wetlands for small
      communities: pilot and full-scale evidence.
AB  - Phosphorus (P) removals in constructed wetlands (CWs) have received particular
      attention in recent decades by using specific materials which promote
      adsorption/precipitation mechanisms. Recent studies have shown interest in using
      apatite materials to promote P precipitation onto the particle surface. As
      previous trials were mainly done by lab experiments, this present study aims to
      evaluate the real potential of apatites to remove P from wastewater in pilot
      units and a full-scale plant over a 2 year period. P retention kinetics of two
      qualities of apatites are presented and discussed. In this work apatite appears
      to have high retention capacity (>80% of P removal) and is still an interesting
      way for P removal in CWs for limiting the risk of eutrophication downstream of
      small communities. Nevertheless, the apatite quality appears to be of great
      importance for a reliable and long term P removal. The use of materials with low
      content of apatite mineral (40-50%) seems to be not economically relevant.

PMID- 21866762
TI  - Decolourization performance in C. I. Vat Yellow 1 aqueous suspension using
      hydrophobically modified poly(acrylic acid).
AB  - A series of hydrophobically modified poly(acrylic acid) (PAA), poly(2
      phenoxyethyl acrylate-co-acrylic acid) (poly(PHEA-co-AA)), have been synthesized
      and characterized by Ubbelohde type viscometry, Nuclear Magnetic Resonance (1H
      NMR) spectrometry and Differential Scanning Calorimetry (DSC). The shear thinning
      Non-Newtonian fluid behavior of their aqueous solution and the dependence on pH
      and hydrophobic group contents were found through apparent viscosity and
      rheological property investigating. Decolourization performance in C. I. Vat
      Yellow 1 aqueous suspension was evaluated through visible absorbance data.
      Decolourization performance of hydrophobically associated polymer indicates two
      times better than that of PAA. The quantitative relationship was mainly studied.

PMID- 21866763
TI  - Simultaneous decolorization of binary mixture of reactive yellow and acid violet
      from wastewaters by electrocoagulation.
AB  - Dyes are common pollutants in a large variety of industrial wastewaters, and the
      treatment of these wastes has been extensively studied by coagulation. For the
      removal of pollutants from the wastewaters, different techniques have been used
      and electrocougulation is one of the widely used methods. This process is very
      effective in removing organic pollutants including dyestuff wastewater. The
      purposes of this study were to investigate the effects of the operating
      parameters, such as current density, electrolyte concentration, dyestuff
      concentration, and pH of solution on decolorization and chemical oxygen demand
      (COD) removal of wastewater containing two different dyes in same solution by
      direct current electrocoagulation. The amount of dye removed was found by
      application of first derivative spectrophotometric method to the synthetic dye
      mixtures. In this work synthetic dye mixture which include C.I. Reactive Yellow
      145 (RY145) and C.I. Acid Violet 90 (AV 90) were used for electrocougulation (EC)
      process with iron electrodes. In the presence of both dye molecules, the optimum
      pH was found to be 4, optimum NaCI concentration was 3000 mg/L and optimum
      current density was 5.56 mA/cm2. Under these conditions in the case of 100 mg/L-1
      each dye concentration at 20 degrees C and 3 cm interelectro distance the color
      removal efficiency was reached 97.7% for AV 90 and 97.1% for RY145 in 10 minutes
      time duration. Dye concentration dependent highest COD removal efficiency was
      measured as 82% around at 100 mg/L dye concentration.

PMID- 21866764
TI  - Catalytic ozonation of aqueous phenol over metal-loaded HZSM-5.
AB  - The performances of HZSM-5 and transition metal-loaded HZSM-5 (Mn, Cu, Fe, Ti)
      catalysts during catalytic ozonation of phenol have been investigated. It was
      observed the performance order for removal of phenol and COD was Mn/HZSM-5 >
      Fe/HZSM-5 > Cu/HZSM-5 > Ti/HZSM-5 > HZSM-5. The presence of metals on HZSM-5
      enhanced the phenol removal capability of HZSM-5. Mn loading on HZSM-5 was
      optimized due to its high phenol removal capability amongst metal-loaded HZSM-5
      catalysts. Experimental results suggested that low amount of Mn loading on HZSM-5
      was sufficient for HZSM-5 to act as catalyst and adsorbent. A maximum of 95.8 wt%
      phenols and 70.2 wt% COD were removed over 2 wt% Mn/HZSM-5 in 120 min. It was
      supposed that transition metals mainly acted as ozone decomposers due to their
      multiple oxidation states that enhanced the ozonation of phenol.

PMID- 21866765
TI  - Estrogen-like and dioxin-like organic contaminants in reclaimed wastewater:
      transfer to irrigated soil and groundwater.
AB  - In semi-arid regions, treated wastewater reuse for irrigation is a common
      practice since wastewater is considered as a non negligible water resource in
      these areas. However, treated wastewater contains traces of organic compounds
      which may contaminate the receiving environment i.e. soil and groundwater. Some
      of these organic compounds have the ability to bind to estrogen receptor (ER) or
      dioxin receptor (AhR, aryl hydrocarbon receptor). The fate of these compounds in
      effluent reused for irrigation, irrigated soils and groundwater is not well
      addressed yet. In the present study, estrogenic and dioxin-like activities were
      studied in three media: i) effluents reused for irrigation, ii) soils samples
      collected from the reclaimed water irrigated plot during six month irrigation,
      and iii) groundwater sampled before and after irrigation periods. Effluents
      reused for irrigation exhibited ER and AhR activities at 38.5 +/- 9.9 ng
      estradiol-equivalent/L (ng E2-EQ/L) and 113.3 +/- 27.7 ng dioxin-equivalent/L (ng
      TCDD-EQ/L), respectively. Soils showed ER activity (0.05 ng E2-EQ/g) only after 4
      months of irrigation. AhR activities detected in all soil samples have not
      changed during irrigation. In groundwater, ER activities were detected in two
      piezometers indicating transfer of some estrogenic compounds.

PMID- 21866766
TI  - Removal of benzene from wastewater via Fenton pre-treatment followed by enzyme
      catalyzed polymerization.
AB  - This study investigated the feasibility of a two-step process for the removal of
      benzene from buffered synthetic wastewater. Benzene is outside the scope of
      enzymatic removal. In order to remove it from wastewater using enzyme, its
      pretreatment by modified Fenton reaction was employed to generate the
      corresponding phenolic compounds. In the first phase, the optimum pH, H2O2 and
      Fe2+ concentrations and reaction time for the Fenton reaction were determined to
      maximize the conversion of benzene to phenolic compounds without causing
      significant mineralization. The pretreatment process was followed by oxidative
      polymerization of the phenolic compounds catalyzed by a laccase from Trametes
      villosa. Factors of interest for the three-hour enzymatic treatment were pH and
      laccase concentration. Under optimum Fenton reaction conditions, 80% conversion
      of the initial benzene concentration was achieved, giving a mixture containing
      oxidative dimerization product (biphenyl) and hydroxylation products (phenol,
      catechol, resorcinol, benzoquinone and hydroquinone). Enzymatic removal of
      biphenyl and benzoquinone was not possible but 2.5 U/mL laccase was successful in
      removal of the rest of the phenolic

PMID- 21866767
TI  - Concentrations and fate of sugars, proteins and lipids during domestic and agro
      industrial aerobic treatment.
AB  - This work investigates the composition and the fate of sugars, lipids, proteins,
      amino acids under aerobic conditions for 13 domestic and 4 agro-industrial
      wastewaters, sampled before and after treatment. The rates of aerobic degradation
      were moreover studied with a 21-day continuous aeration batch test. It is shown
      that the sum of the biochemical forms represented 50 to 85% of the total chemical
      oxygen demand (COD). Lipids represented the half of the identified COD; sugars
      and proteins correspond to a quarter of the identified COD. Aerobic processes
      provided an increase of the relative fractions for proteins, whereas the ones of
      lipids decreased and sugars fraction remains stable. For the wastewaters released
      from cheese dairy (lipid-rich) and slaughterhouses (protein/lipid-rich), the
      dissolved phase after biological treatment is composed of proteins whereas the
      particulate one is composed of lipids. After the 21-day test, the concentration
      in proteins was nearby 10 mg/L. The results should be used for operations of WWTP
      to detect when a dysfunction is about to occur. They can be used to predict the
      concentrations in the treated water when upgrading an existing municipal plant
      that will admit agro-industrial discharge.

PMID- 21866768
TI  - Effects of wastewater irrigation on soil properties and turfgrass growth.
AB  - Reuse of treated wastewater for turf irrigation is often viewed as one way to
      maximize existing urban water resources. The aim of this study is to evaluate the
      applicability of treated wastewater for turfgrass and assess the effects of
      continuous use of treated water on the soil and crop. Two turfgrass plots
      irrigated with drinking water and treated wastewater were monitored over a two
      year period. Physical and chemical parameters in the soil and foliar tissue were
      analyzed. Plants irrigated with treated wastewater had highest sodium content.
      There were no negative effects with respect to changes in soil pH but a
      significant increase in electrical conductivity and sodium content was observed
      in wastewater-irrigated soil. Treated wastewater could be used as a resource for
      agricultural irrigation since it contributes phosphorus and organic matter.
      However, it is necessary to consider that several crops could be negatively
      affected by wastewater irrigation because of the sodium content and this should
      be taken into account when water-sprinklers are in use, since this is the case in
      the present study. The benefits of irrigation with treated urban wastewater
      include contributing plant nutrients to turfgrass while conserving freshwater.

PMID- 21866769
TI  - Phosphate release from waste stabilisation pond sludge: significance and fate of
      polyphosphate.
AB  - Net phosphorus removal from waste stabilisation pond (WSP) systems is governed by
      the rate of phosphorus incorporation into the sludge layer and the rate of
      phosphorus release from this sludge back to the overlying wastewater. Luxury
      uptake of phosphorus by microalgae has been shown to occur under WSP conditions
      in the laboratory; however, the significance of this mechanism and the fate of
      polyphosphate contained in the settled solids have not previously been
      investigated. In this work the analysis of sludge samples from three WSP showed
      that up to 71% of the total phosphorus in the sludge was in the form of
      polyphosphate. This indicates that polyphosphate accumulation could potentially
      be an important mechanism for phosphorus sequestration in WSP and challenges the
      common view that chemical precipitation is the predominant phosphorus removal
      mechanism in these systems. The release of phosphate from WSP sludge samples was
      monitored in the laboratory. The samples from two different pond systems had
      release rates in the order of 4.3 microgP/gTSS.d. However, the third sample which
      was collected during an algal bloom had a release rate of 12.4 microgP/gTSS.d.
      Phosphate release from fresh microalgal sludge grown under laboratory conditions
      was also studied and was shown to have a release rate of 160 microgP/gTSS.d.
      Analysis of polyphosphate during the experiments on laboratory grown microalgal
      sludge showed that polyphosphate was indeed degraded resulting in phosphate
      release. Interestingly, after the initial release phase phosphorus was
      assimilated by the biomass and some polyphosphate was reformed. It is likely that
      this is due to bacterial growth in the sludge.

PMID- 21866770
TI  - Dehydration of water/pyridine mixtures by pervaporation using cellulose acetate/
      polyacrylonitrile blend membrane.
AB  - Cellulose acetate/ polyacrylonitrile (CA/PAN) membranes were prepared and used to
      separate pyridine / water mixtures by pervaporation. The membranes were
      characterized through SEM. The effects of feed concentration, operation
      temperature and downstream pressure on the separation performance were evaluated.
      Experimental results indicated the increase of operation temperature could raise
      the permeation flux and the separation factor, while increasing feed
      concentration and downstream pressure would raise the separation factor and
      decrease the permeation flux. Under the conditions that pyridine solution was 99
      wt.%, operation temperature was 323 K and downstream pressure was 20 mmHg, the
      CA/PAN blend membrane showed its best separation performance that the permeation
      flux was 56.g.m-2 h-1 and the separation factor was 182.

PMID- 21866771
TI  - The effect of mixed liquor suspended solids (MLSS) on biofouling in a hybrid
      membrane bioreactor for the treatment of high concentration organic wastewater.
AB  - Biofouling is a crucial factor in membrane bioreactor (MBR) applications,
      particularly for high organic loading operations. This paper reports a study on
      biofouling in an MBR to establish a relationship between critical flux, Jc, mixed
      liquor suspended solids (MLSS) (ranging from 5 to 20 g L-1) and volumetric
      loading rate (6.3 kg COD m-3 h-1) of palm oil mill effluent (POME). A lab-scale
      100 L hybrid MBR consisting of anaerobic, anoxic, and aerobic reactors was used
      with flat sheet microfiltration (MF) submerged in the aerobic compartment. The
      food-to-microorganism (F/M) ratio was maintained at 0.18 kg COD kg-1 MLSSd-1. The
      biofouling tendency of the membrane was obtained based on the flux against the
      transmembrane pressure (TMP) behaviour. The critical flux is sensitive to the
      MLSS. At the MLSS 20 g L-1 the critical flux is about four times lower than that
      for the MLSS concentration of 5 g L-1. The results showed high removal efficiency
      of denitrification and nitrification up to 97% at the MLSS concentration 20 g L
      1. The results show that the operation has to compromise between a high and a low
      MLSS concentration. The former will favour a higher removal rate, while the
      latter will favour a higher critical flux.

PMID- 21866772
TI  - Estimating the risk from sewage treatment plant effluent in the Sydney catchment
      area.
AB  - This study employed Quantitative Microbial Risk Assessment (QMRA) to estimate the
      gastrointestinal risks associated with Cryptosporidium and Giardia discharged
      from three STPs located within the Lake Burragorang catchment. The QMRA
      considered baseline and various hazardous event scenarios (e.g. plant failure and
      heavy rainfall). Under baseline conditions, the combined effect of constructed
      barriers, catchment barriers and dilution reduced pathogen numbers from the
      discharge of all three STPs by 10 to 14 orders of magnitude. This was sufficient
      for the risk to be well below currently mooted benchmarks of 'tolerable risk',
      even when relatively conservative assumptions were applied. For all hazardous
      event scenarios, the level of risk remained low, which illustrated the benefit of
      multiple barriers. Provisionally it appears that the STPs currently discharging
      into the waterways of the catchment do not pose an unacceptable or unmanageable
      risk to Sydney's drinking water consumers.

PMID- 21866773
TI  - Nanofiltration for enhanced removal of disinfection by-product (DBP) precursors
      in swimming pool water-retention and water quality estimation.
AB  - Three nanofiltration (NF) membranes with a chlorine tolerance > or = 1 mg L-1
      were applied to reduce DBPs and their precursors in swimming pool water. A lab
      scale plant with crossflow modules was installed in by-pass at the sand filter
      outlet of a swimming pool for a period of several weeks. The chlorine tolerances
      of the membranes SB90 and NP030 were found to be adequate for filtration under
      swimming pool water conditions over the given experimental period. Retention of
      dissolved organic carbon (DOC) and adsorbable organic halogens (AOX) were about
      70% and 80% for SB90 and 50% and 40% for NP030, respectively. DOC accumulation in
      the pool and the expected fresh water consumption for a treatment system
      consisting of ultrafiltration (UF) and NF with backwash water treatment were
      estimated by mass balances based on the results. Mass balances were calculated
      also for a German public swimming pool with a conventional water treatment system
      (flocculation-sand filtration-chlorination) and were compared to DOC on-line
      measurements. Calculation of DOC mass balances for different UF-NF treatment
      scenarios showed that pool water quality could be improved significantly compared
      to the conventional treatment system.

PMID- 21866774
TI  - Shall we upgrade one-dimensional secondary settler models used in WWTP
      simulators? - An assessment of model structure uncertainty and its propagation.
AB  - In WWTP models, the accurate assessment of solids inventory in bioreactors
      equipped with solid-liquid separators, mostly described using one-dimensional (1
      D) secondary settling tank (SST) models, is the most fundamental requirement of
      any calibration procedure. Scientific knowledge on characterising particulate
      organics in wastewater and on bacteria growth is well-established, whereas 1-D
      SST models and their impact on biomass concentration predictions are still poorly
      understood. A rigorous assessment of two 1-DSST models is thus presented: one
      based on hyperbolic (the widely used Takacs-model) and one based on parabolic
      (the more recently presented Plosz-model) partial differential equations. The
      former model, using numerical approximation to yield realistic behaviour, is
      currently the most widely used by wastewater treatment process modellers. The
      latter is a convection-dispersion model that is solved in a numerically sound
      way. First, the explicit dispersion in the convection-dispersion model and the
      numerical dispersion for both SST models are calculated. Second, simulation
      results of effluent suspended solids concentration (XTSS,Eff), sludge
      recirculation stream (XTSS,RAS) and sludge blanket height (SBH) are used to
      demonstrate the distinct behaviour of the models. A thorough scenario analysis is
      carried out using SST feed flow rate, solids concentration, and overflow rate as
      degrees of freedom, spanning a broad loading spectrum. A comparison between the
      measurements and the simulation results demonstrates a considerably improved 1-D
      model realism using the convection-dispersion model in terms of SBH, XTSS,RAS and
      XTSS,Eff. Third, to assess the propagation of uncertainty derived from settler
      model structure to the biokinetic model, the impact of the SST model as sub-model
      in a plant-wide model on the general model performance is evaluated. A long-term
      simulation of a bulking event is conducted that spans temperature evolution
      throughout a summer/winter sequence. The model prediction in terms of nitrogen
      removal, solids inventory in the bioreactors and solids retention time as a
      function of the solids settling behaviour is investigated. It is found that the
      settler behaviour, simulated by the hyperbolic model, can introduce significant
      errors into the approximation of the solids retention time and thus solids
      inventory of the system. We demonstrate that these impacts can potentially cause
      deterioration of the predictive power of the biokinetic model, evidenced by an
      evaluation of the system's nitrogen removal efficiency. The convection-dispersion
      model exhibits superior behaviour, and the use of this type of model thus is
      highly recommended, especially bearing in mind future challenges, e.g., the
      explicit representation of uncertainty in WWTP models.

PMID- 21866775
TI  - Is modeling of biological wastewater treatment a mature technology?
AB  - Based on three case studies it is demonstrated that the application of
      mathematical models in biological wastewater treatment has not yet reached its
      full potential. Model structure uncertainty and correlation of uncertain
      parameter values make up the first case. The combination of biokinetic and
      hydraulic models relates to the second case. The evolution of a full scale plant
      over its life expectancy is the frame for the third case. This paper was
      initially presented as a discussion starter and thus is raising questions rather
      than providing answers.

PMID- 21866776
TI  - Enteric viruses in New Zealand drinking-water sources.
AB  - This study determined whether human pathogenic viruses are present in two New
      Zealand surface waters that are used as drinking-water sources. Enteric viruses
      were concentrated using hollow-fibre ultrafiltration and detected using PCR for
      adenovirus (AdV), and reverse transcription PCR for norovirus (NOV) genogroups I
      III, enterovirus, rotavirus (RoV) and hepatitis E virus (HEV). Target viruses
      were detected in 106/109 (97%) samples, with 67/109 (61%) samples positive for
      three or more viral types at any one time. AdV, NoV and ROV were detected the
      most frequently, and HEV the least frequently. Human NoV was not usually
      associated with animal NOV. Our results suggest that New Zealand would be well
      served by assessing the ability of drinking-water treatment plants to remove
      viruses from the source waters, and that this assessment could be based on the
      viral concentration of AdV-NoV-RoV. The long-term aim of our work is to use this
      information to estimate the risk of waterborne viral infection.

PMID- 21866778
TI  - Nutrient removal in wastewater treatment high rate algal ponds with carbon
      dioxide addition.
AB  - The influence of CO2 addition to high rate algal ponds (HRAPS) on nitrogen
      removal was investigated using two pilot-scale HRAPs operated with different
      hydraulic retention times (HRT: 4 and 8 days), and was compared to the nitrogen
      removal by the 8-day HRT pond before CO2 addition was installed. Nitrogen
      balances were calculated by partitioning total nitrogen into organic and
      inorganic nitrogen (NH4+-N and NO3--N), and by separation of the organic nitrogen
      into particulate (PON) and dissolved organic nitrogen (DON). PON was further
      divided into algal organic nitrogen (AON) and bacteria organic nitrogen (BON) to
      investigate nitrogen mass flow in the HRAPS. This research shows that the
      proportion of algae in the algal/bacterial biomass in the longer 8-day HRT HRAP8d
      (55.6%) was appreciably lower than that in the shorter 4-day HRT HRAP4d (80.5%)
      when CO2 was added to control the maximum pH to <8.0 during the summer. Higher
      bacterial biomass in the longer 8-day HRT HRAP corresponded with higher
      nitrification rates, indicating that the longer 8-day HRT in the summer was
      detrimental for two reasons: lower algal productivity and increased nitrogen loss
      through nitrification/denitrification. Overall nitrogen removal of approximately
      60% in the HRAPS with CO2 addition was mainly achieved by algal assimilation
      followed by sedimentation in the settling unit.

PMID- 21866777
TI  - Influence of nitrogen limitation on performance of a microbial fuel cell.
AB  - We describe the operation of a microbial fuel cell (MFC) system operating on a
      synthetic wastewater (acetic acid), under conditions of increasing nitrogen
      limitation. Two MFCs were operated under feed conditions which spanned a range of
      TKN/COD values of 1.6-28 mg/g. Stable operation was observed in all cases, even
      when no ammoniacal nitrogen was added to the cell. Improved electrochemical
      performance (measured as power density, W/m2) was observed as nitrogen limitation
      was imposed on the cells. Even with no ammonium addition, continuous function of
      the cell was maintained, at levels consistent with operation at balanced nutrient
      supplementation. The work has implicated biological nitrogen fixation as a
      potential source of nitrogen within the MFC. Whilst this hypothesis has yet to be
      confirmed, the work highlights the opportunity for continuous operation of
      microbial fuel cells utilising wastewaters with extremely low nitrogen levels,
      present in pulp and paper, pharmaceutical and petrochemical industries. Further,
      the described increases in some of the electrochemical indices (e.g. power
      density) under application of nitrogen limitation may provide a new approach to
      increasing fuel cell performance. Finally, the lack of any need to add
      supplemental nitrogen to a MFC-based wastewater treatment technology holds
      potential for significant financial and environmental savings.

PMID- 21866779
TI  - Potential contribution of the wastewater sector to energy supply.
AB  - The biological treatment of wastewater could yield high energy fuels such as
      methane and alcohols, however most conventional treatment systems do not recover
      this energy potential. with a simple model of the energy yields of various
      wastewater treatment technologies it is possible to demonstrate how minor shifts
      in technology selection can lead the industry from being identified as
      predominantly energy intensive, to being recognised as a source of energy
      resources. The future potential energy yield is estimated by applying energy
      yield factors to alternative use scenarios of the same wastewater loads. The
      method for identifying the energy potential of wastewater was demonstrated for
      the New Zealand wastewater sector, but can equally be applied to other countries
      or regions. The model suggests that by using technologies that maximise the
      recovery of energy from wastewater, the potential energy yield from this sector
      would be substantially increased (six fold for New Zealand).

PMID- 21866780
TI  - Fluxes of 13 selected pharmaceuticals in the water cycle of Stockholm, Sweden.
AB  - Mass flows of 13 pharmaceutical active ingredients (APIS) found in drinking water
      were studied in the water cycle of Stockholm. Data were collected by analyzing
      samples of surface water, raw water and drinking water as well as influents,
      effluents and sludges from waste water treatment plants (WWTPs) in Stockholm
      area. A mass balance was performed, based on sold amounts of pharmaceuticals and
      the measured concentrations in water and sludge. The selected APls were all
      present in WWTP effluents and the removal rates for many of them were poor. Mass
      balance calculations showed that the three studied WWTPs in Stockholm release
      considerable amounts of the selected APIs into the Baltic Sea while the portions
      ending up in WWTP sludge were significantly lower. The levels of APIs found in
      drinking water are low at present, but may increase in the future unless the
      releases from WWTPs in the catchment of Lake Malaren are mitigated.

PMID- 21866781
TI  - Physico-chemical characterisation versus in situ micro-structural
      characterisation of membrane fouling in membrane bioreactors.
AB  - Fouling characteristics of aerobic submerged membrane bioreactors were analysed
      under two different membrane materials. Polyethersulfone (PES) membranes were
      found to foul faster at sub-critical flux than polyolefin (PO) membranes. Physico
      chemical characterisation, by means of comparison of extracellular polymeric
      substances (EPS) and soluble microbial products (SMP) concentrations, as well as
      the mixed liquor suspended solids (MLSS) concentration were unable to explain the
      differences in membrane fouling of the contrasting membrane materials. The use of
      confocal laser scanning microscopy (CLSM) to image organic foulants directly on
      the membrane surface, coupled with image analyses showed that membrane fouling
      mechanism shifted from a biofilm initiated process on PO membranes to a bio
      organic dominated process on PES membranes under sub-critical flux conditions.
      These results show that physico-chemical characterisation of an MBR process may
      not effectively distinguish the effectiveness of different membrane materials, so
      long as operating conditions are identical, and that characterisation of foulants
      on the membrane surfaces was necessary to elucidate the differences in membrane
      fouling.

PMID- 21866782
TI  - Sorption of Pb(ll) by poly(hydroxamic acid) grafted oil palm empty fruit bunch.
AB  - This paper describes the sorption of Pb(ll) from aqueous solution. Oil palm empty
      fruit bunch (OPEFB) fiber was first grafted with poly(methylacrylate) and then
      treated with hydroxylammonium chloride in alkaline medium to produce hydroxamic
      acid (PHA) grafted OPEFB. Sorption of Pb(ll) by PHA-OPEFB was maximum at pH 5.
      The sorption followed the Langmuir model with maximum capacityof 125.0 mg g-1 at
      25 degrees C. The sorption process was exothermic, as shown by the negative value
      of enthalpy change, Delta H0. The free energy change (DeltaG0) for the sorption
      was negative, showing that the sorption process was spontaneous. A kinetic study
      showed that the Pb(ll) sorption followed a second order kinetic model.

PMID- 21866783
TI  - [Science, reason for the existence of the University].
AB  - More than a century after the foundation of the illustrious University of Zulia,
      research is still the subject of unfair treatment; the importance of science in
      university life is discussed over and over again, with authorities feeling proud
      of the quantity and quality of researchers, but such pride is divorced from the
      support received by research centers, departments and institutes. However,
      science transcends all obstacles; research must be the ultimate goal of our
      University, so that it continues to be the University.

PMID- 21866784
TI  - [No deletion alpha thalassaemia in Spain. Abnormal hematological index and
      molecular study].
AB  - The alpha thalassaemia diseases in most cases are caused by deletions that affect
      one or two of the alpha genes, being less frequent the cases due to punctual
      mutations, insertions or deletions of a few pairs of bases, which have been
      denominated no deletion a thalassaemias. The objective of this investigation was
      to determine the incidence of the no deletion alpha thalassaemia in patients with
      a thalassaemia using molecular biology techniques. We studied 517 individuals of
      the San Carlos Hospital (Thalassemia Molecular Research Center, Madrid-Spain)
      between January 2001 and December 2003, in whom iron deficiency anemia had been
      ruled out, that presented microcytosis and hypochromia and that presented normal
      HbA2, HbF and EEF from normal Hbs. The two types of no deletion a thalassaemia
      most frequently described in the Mediterranean were studied: 1) alpha Hph due to
      deletion of 5bp in the IVS I and 2) alphaNco due to a change in the initiation
      codon of the gene. Of the 517 cases studied, 40 (7.7% of the cases) represented a
      no deletion alpha thalassaemia. Of these cases, 28 were positive for alphaHph of
      the alpha2 gene, 24 in the heterozygote state, one homozygote and three double
      heterozygotes associated with the 3,7 kb deletion. The remaining 12 cases were
      positive for the alphaNco of the alpha2 gene, 10 heterozygotes, one homozygote
      and one double heterozygote associated with the 4,2 kb deletion. The no deletion
      alpha thalassaemias represent < 8% from the cases in our environment. The
      alphaHph is the most frequent type of no deletion a thalassaemia and its
      haematological abnormalities are more manifest that the ones present in the cases
      of alphaNco.

PMID- 21866785
TI  - A combined proteomic and immunologic approach for the analysis of Schistosoma
      mansoni cercariae and adult worm protein extracts and the detection of one of the
      vaccine candidates, Sm28GST, from a Venezuelan parasite isolate.
AB  - Understanding the mode of Schistosoma mansoni larval invasion and the mechanism
      of immune evasion utilized by larvae and adult worms is essential for a rational
      development of vaccines or drugs to prevent or cure the disease. This parasite
      has a very complex molecular organization in all parasite stages, and identifying
      the major parasite proteins would give clues to schistosome metabolism and to the
      interaction of the parasite with the host immune system. Our goal was the
      evaluation of the protein parasite repertoire using a proteomic approach, and the
      characterization of protein extracts from two different parasite stages of a
      Venezuelan isolate, such as cercariae and adult worms, previously performed by
      other authors in some other strains. A comparison among authors was made.
      Besides, we aimed to identify different isoforms of one of the vaccine
      candidates, the gluthation-S-transferase protein (Sm28GST), by 2D SDS-PAGE and
      mass spectrometry, and to achieve its immunologic detection using sera from
      rabbits immunized with synthetic peptides derived from the Sm28GST protein. These
      techniques allowed the identification of some of the target molecules of the
      protective immune response that are being evaluated as potential members of a
      multi-component and multi-stage anti-S. mansoni vaccine and to clarify if the
      selected peptides induce antibodies that are able to recognize different isoforms
      of the Sm28GST.

PMID- 21866786
TI  - [Effect of the intake of an integral bread formulated with gum from Hymenaea
      courbaril on the concentrations of blood lipids of patients with mild-moderate
      dyslipidemia].
AB  - The seeds of Hymenaea courbaril (Caesalpiniace), a species widely disseminated in
      Venezuela, produce a clear and soluble gum. The dietetic fiber content (60.7%) of
      the gum was used as a good criterion for the formulation of integral bread in a
      diet for dyslipidemia patients. The proximal composition of the integral bread
      was determined. The product acceptability evaluation was done by a comparison
      test and by a hedonic scale. The experimental design was carried out with a total
      of 30 male volunteers with dyslipidemia. They were divided into two groups: Group
      A was fed with a modified diet, which included bread prepared with the H.
      courbaril gum; and Group B received the same diet without the gum, based on the
      American Dietetic Association recommendations. Both groups were maintained on
      their respective diets for six weeks. The lipid profile was determined in each
      patient, before starting the diets and after the specified period. The bread
      formula contained 17.60% protein, 1.19% fat and 0.97% crude fiber, in accordance
      with standards established by COVENIN. The paired preference test showed grater
      acceptance of the bread prepared with a gum concentration of 7% and low fat
      content. Significant decreases in the concentrations of triacylglycerol and VLDL
      cholesterol were observed in Group A. These findings suggest a possible use of
      the H. courbaril gum, as a diet modifier for dyslipidemic patients.

PMID- 21866787
TI  - [Trypanosoma cruzi infection in pregnant mice induces a cellular immune response
      with citokines production in their fetuses].
AB  - The objective of this study was to detect the cytokines IFN-gamma, IL-4 and IL-10
      expressed by CD4+ T cells in tissues of fetal mice with acute chagasic infection.
      For this, we examined the fetuses of NMRI mice whose mothers were infected with
      22x10(3) metacyclic trypomastigotes of the M/HOM/BRA/53/Y strain of T. cruzi and
      made pregnant during the acute phase of infection. For the detection and
      localization of inflammatory infiltrates, nest parasites, antigens of T. cruzi a
      nd cytokines w eused hematoxylin-eosin techniques, peroxidase-anti-peroxidase and
      immunofluorescence. The immunohistochemical study revealed the presence of
      inflammatory infiltrates and antigens with amastigote nests in fetal skeletal
      muscle. CD4 + T cells producing IFN-gamma, as well as deposits of IFN-gamma and
      IL-10, were detected in sections of placenta, heart and skeletal muscle of
      fetuses of mice infected, while CD4+/IL-10+ was found only in skeletal muscle; in
      addition, deposits of IL-4 were detected only in placentas of healthy mice. These
      results indicate that fetuses are capable of generating their own immune response
      to antigens transmitted by their mother, which induces the secretion of cytokines
      and that, acting in synergy with the maternal antibodies, confer them a state of
      protection against infection; and that the transmission of the parasite depends
      on factors specific to each mother, which may modify its ability to control such
      transmission at the placental or systemic levels.

PMID- 21866788
TI  - [HPV infection associated with nonclassic cytological signs in patients from
      Merida, Venezuela].
AB  - The purpose of this work was to identify those nonclassic cytological signs that
      would allow the prediction of human papillomavirus (HPV) infection. Cytology
      samples taken from outpatients that attended public and private gynecological
      practices, between January of 2006 and December of 2008, were studied. The
      cytological samples were informed following the criteria of the Bethesda system
      2001. Those reports with a cytological interpretation of low-grade squamous
      intraepithelial lesion/HPV (LSIL/HPV) were selected. Age data and other cytologic
      characteristics were also taken. 25,565 Pap smears were revised, of which 291
      were LSIL/HPV. The age average of the patients was 32.01 years and the age range
      was between 15 and 67 years. 55.10% of the patients were below 30 years of age.
      The koilocytosis was the most frequent viral cytological sign (66.1%). Among the
      HPV infection associated nonclassic cytologic signs were in order of frequency:
      nuclear enlargement (44%), megalocytosis (38.5%), followed by binucleation and
      lightly irregular chromatin distribution, in the same proportion (33.7%) and the
      typical parakeratotic cells (33.3%). Discreet nuclear hyperchromasia and hiper
      keratotic cells were the less frequent morphological changes (28.5%). The
      indirect signs significantly associated to the infection were: binucleation,
      lightly irregular chromatin distribution, discreet nuclear hyperchromasia and
      para-keratotic cells. The combination of HPV infection associated with nonclassic
      cytological signs would allow the identification of a high proportion of patients
      with this infection, increasing in this way the sensibility of the cytological
      study in the detection of HPV and the possibility of selecting subgroups at risk
      for the development of cervical lesions and their opportune study.

PMID- 21866789
TI  - [Synchronic hepatocellular carcinoma with atrial myxoma. A case report].
AB  - The case of a 60-year-old woman with history of cryptogenic hepatic cirrhosis and
      a probable hepatic tumor, who died of upper gastrointestinal bleeding secondary
      to esophageal varices, is presented. An autopsy study was carried out, which
      showed a hepatocellular carcinoma and a left atrial cardiac myxoma with glandular
      elements. A review of the literature, searching for the association between these
      two tumors, in addition to other tumors, is presented.

PMID- 21866790
TI  - [Immunology of pregnancy].
AB  - One of the phenomena that offers more questions in Immunology is: Why the embryo,
      behaving like a semialogenic graft, is not rejected by the mother? It is known
      that the mother produces an active immunological response against the fetus and,
      nevertheless, in normal conditions, the immunological rejection does not take
      place. In the present work of revision, some mechanisms are described by means of
      which the specific immunological tolerance of the mother is generated towards the
      embryo. All these mechanisms are interdependent and altogether they constitute a
      safety network to avoid the fetal rejection. Here the effects of female sex
      hormones on the immunological system, the change of the profile of cytokines, the
      generation of immunomodulating proteins and blocking antibodies, the effect of
      the expression of the HLA-G and the paper of some cells, like Regulatory T
      lymphocytes, dendritic and Natural Killer cells, are detailed. Also other routes
      by which the embryo defends itself of the maternal immunological attack are
      described, like the induction of apoptosis in the endometrium and leukocytes, the
      tryptophan and iron metabolisms, the inhibition of the complement system and the
      expression of annexins.

PMID- 21866791
TI  - [Attention-deficit / hyperactivity disorder in autism spectrum disorders].
AB  - According to the DSM-IV-TR, symptoms of inattention and hyperactivity are
      frequent in children with Autism Spectrum Disorders (ASD). This statement is
      supported by clinical observation and formal assessment. However, ASD diagnosis
      is still among the exclusion criteria for the Attention-Deficit/Hyperactivity
      Disorder (ADHD). Such exclusion generates controversy and questions regarding the
      need and benefits of maintaining or not these separations; so much so, that the
      proposed criteria for the DSM-V eliminate that exclusion condition. It is
      necessary a better understanding of the comorbidity between both entities in
      order to be able to have an appropriate sequence of the intervention goals. For
      that reason, if inattention and hyperactivity in individuals with ASD are
      considered as a representation of a comorbid diagnosis of ADHD, treatment plans
      for this group would be better adjusted and more likely to offer a real benefit
      in the outcome of their adaptive functioning.

PMID- 21866792
TI  - The inflammatory cells in vascular graft anastomosis an electron microscopy
      study.
AB  - In order to determine the processes arising during the healing in vascular grafts
      the following experiment was desinged in 16 dogs. MATERIAL AND METHODS: The
      animals underwent implantation of unilateral bypass aorto-femoral (straight
      prosthesis from politetrafluoroethylrne--PTFE). After the 6 months all the
      animals sacrificed and vascular grafts were dissected and exam in electron
      microscopy. RESULTS: There were significant differences in the histological
      findings in structure of neoitima between the proximal and distal anastomoses
      vascular prostheses. There were evidence of presence of fibroblasts but not
      macrophages in proximal anastomoses The histological structure of the proximal
      anastomoses indicates that inflammatory processes was ended during the prosthesis
      healing. There were presence of macrophages and myofibroblasts, some in the
      active secretion of collagen in distal anastomoses. CONCLUSIONS: Theses images of
      vascular anastomoses of artery with politerafluoroeth-ylene prosthesis
      corresponds to the chronic inflammatory reaction in distal anastomoses.

PMID- 21866793
TI  - Investigation of free volume changes in the structure of the polymer bifocal
      contact lenses using positron lifetime spectroscopy PALS.
AB  - Positron annihilation lifetime spectroscopy PALS has been applied of free volume
      properties in bifocal contact lenses. The measurements have been made on new
      lenses and then after one, two, three and four weeks wear. The longest lifetime,
      obtained via three-component analyses of the spectra, was associated with the
      pick-off annihilation of ortho-positronium trapped in the free volume. After wear
      of the lenses changes in the ortho-positronium lifetimes and the relative
      intensity of the longest component were observed. These results are discussed on
      the basis of a free volume model.

PMID- 21866794
TI  - Formulation and evaluation of mucoadhesive matrix tablets of taro gum:
      optimization using response surface methodology.
AB  - The present study was aimed to formulate and evaluate oral controlled release
      mucoadhesive matrix tablets of taro gum incorporating domperidone as model drug.
      Tablets were prepared by direct compression and were evaluated for bioadhesive
      strength and in vitro dissolution parameters. A central composite design for 2
      factors, at 3 levels each, was employed to evaluate the effect of criti cal
      formulation variables, namely the amount of taro gum (X1) and PVP K 30 (X2), on
      mucoadhesive strength, tensile strength, release exponent (n) and t50 (time for
      50% drug release). The mucoadhesive detachment force (evaluated using texture
      analyzer) was found to be 18.266, 54.684 and 65.904 N for A4, A5 and A6 batches
      of the formulated tablets. The polynomial equation indicates that taro gum has
      dominating effect on mucoadhesive strength and both X1 and X2 have almost equal
      and comparable effect on tensile strength. The drug release follows first order
      kinetics (release of drug depends on remaining concentration of drug) and shows
      best linearity (r2 = 0.983) with higuchi model. The release exponent (n) lies
      between 0.339 and 0.543 indicating drug release from the matrix tablets may be
      fickian or non fickian (anamolous) depending upon the concentration of natural
      polymer. T50 was 58, 140 and 220 minutes for A7, A8 and A9 batches showing
      overriding potential of taro gum but still the effect of PVP K 30 is noteworthy.
      PVP K 30 has indirect effect on all the factors by increasing tensile strength
      and making the tablet firm and intact.

PMID- 21866795
TI  - [In vitro evaluation of the gels properties prepared on Pluronic F-127 as
      vehicles for administration prolactin by injection].
AB  - The aim of this study was to prepare a thermoresponsive formulations, which are a
      carrier for proteins--prolactin administered directly into solid tumor and which
      obtain sol-gel transitions at physiological ranges of temperature. Prolactin
      (PRL) is a hormone that in vivo and in vitro exhibits antiangiogenic properties.
      Application of this protein in the proposed formulations can be particularly
      advantageous because of its relatively low stability and limited ability to
      transmembrane penetration. The paper prepared thermoresponsive carriers, based on
      nonionic polymer Pluronic F-127 with selected excipients such as dextran 7000,
      PEG 400, Tween 20 and Tween 80. The sol-gel transition temperature of the
      formulations was investigated and their physicochemical properties such as pH,
      density, osmotic pressure were studied. In the remainder of the work carried out
      tests of prolactin release from the proposed media. The results obtained indicate
      that a significant influence on the theological parameters obtained carriers and
      the availability of pharmaceutical composition of prolactin was developed
      formulation.

PMID- 21866796
TI  - [Influence of polymers on hydrogels with hydrocortisone properties].
AB  - Studies on the effect of polymers on physicochemical properties hydrogels for
      topical use. Rheological parameters were tested and pharmaceutical availability
      of hydrocortisone from gels. Formulation of hydrogels with 1% hydrocortisone
      content produced on the basis of methylcellulose, carboxymethlcellulose sodium
      salt and Carbopol 934 P.

PMID- 21866798
TI  - [Description of the membrane transport using Peusner's network thermodynamics:
      relations between Rik, Lik, Hik and Pik coefficients].
AB  - In the paper, using the Kedem-Katchalsky equations in Peusner's version, the
      relations between Rik, Lik, Hik i Pik (i does not = k = 1, 2), coefficients for
      polymeric membrane and nonelectrolytic solutions were derived.

PMID- 21866797
TI  - [Evaluation of the vant'Hoff's osmotic coefficient in concentration polarization
      conditions of membrane system].
AB  - In this paper the method of evaluation the value of osmotic vant't Hoff's
      coefficient (f) in membrane system, which is based on the original equation of
      third degree for the coefficient f was elaborated. This equation, obtained on the
      basis of Kedem-Katchalsky equation, contains the transport parameters of membrane
      (Lp, sigma, omega), solution concentration (C), volume flux (Jvm), thickness of
      concentration boundary layer (delta), etc. These parameters can be determined in
      a series of independent experiments. The calculation performed for the solution
      of ammonia in aqueous solution of KCl and polymer membranes show that, the value
      of coefficient f fulfill the condition 1 < or = f < or = 2 and that there is a
      range of concentrations of ammonia, in which the changes f occur nonmonitically

PMID- 21866799
TI  - [Injury and reparative regeneration of the oral mucosal epithelium after
      cytostatic drugs administration (tissue, cell and molecular mechanisms)].
AB  - This paper presents the systematized summary of current literature data and the
      authors' own findings on the regularities of human and animal surface oral
      mucosal epithelium (OME) injury caused by cytostatic drugs (CSD) administration,
      and on the ways of its regeneration after the cytostatic chemotherapy (CSCT)
      discontinuation. Tissue, cell and molecular mechanisms of CSCT effects on OME,
      are described. The direct effects of CSD included the epithelial layer
      attenuation with the derangement of its architecture, epitheliocyte proliferation
      suppression, apoptosis activation, and differentiation disturbances (involving
      the broad spectrum of cytological, cytochemical, ultrastructural and molecular
      biological changes). In severe cases, these processes resulted in the loss of the
      epithelial layer integrity with the development of ulceration. Complete
      epithelial regeneration requires a long period after the CSCT discontinuation.
      Indirect effects of CSD on OME are associated with the microbial invasion and the
      diffusion of microbial vital activity products into the epithelium with
      concurrent leukopenia, immunosuppression and decreased salivary secretion.

PMID- 21866800
TI  - [Fusion of brain neurons in rat embryos].
AB  - Syncytial interneuronal connections were studied in the sensomotor cortex and
      caudate nucleus of twenty 14-22 day rat embryos. It was shown that with the
      extremely weak development of glial processes, many neuronal bodies and their
      processes were in the direct contact with each other. The contacting membranes in
      these areas formed oblong and dot-like contacts resembling gap and tight
      junctions. As a result, the intercellular cleft experienced varicose-like
      deformations. In the area of contacts, barely visible membrane pores were formed
      that broadened to form large perforations. The perforation margins presented the
      rounded shape of fused plasma membranes of adjacent neurons. Inside the
      perforations, residual vesicular membranous bodies were formed. The areas of the
      paired membranes between perforations were fragmented, thus increasing the number
      of residual vesicles, until the neurons fused with each other completely by
      unifying the neuroplasm of contacting cells. The results of these studies suggest
      that that the fusion of neurons in vertebrate brain cortex and brainstem nuclei
      could occur not only in pathology, but also in normal animals at the stage of
      embryonic development.

PMID- 21866801
TI  - [Vimentin and glial fibrillary acidic protein in the cells of ectopic
      neurotarnsplants of rat neocortex].
AB  - The purpose of this study was to investigate the expression of intermediate
      filament proteins (vimentin and glial fibrillary acidic protein--GFAP) in the
      cells of embryonic rat neocortex at different time points after its
      allotransplantation into injured sciatic nerve of adult animals. Using
      immunohistochemical methods, the differentiation of GFAP-positive astrocytes from
      vimentin-positive radial glial cells was observed in embryonic rat neocortex,
      grafted into sciatic nerve. It was shown that the differentiation of the
      embryonic neocortical astrocytes in the transplants took place a few days earlier
      than in the rat neocortex during normal ontogenesis. Reactive gliosis was
      demonstrated in the long-term transplants, as indicated by a large number of
      intensely stained GFAP-positive cells and vimentin-containing astrocytes. These
      findings suggest that ectopic neurotarnsplants could serve as a model for
      fundamental studies of the mechanisms of reactive gliosis development.

PMID- 21866802
TI  - [Morphometric and histochemical characteristic of cluster organization of the
      neurons of rat spinal nerve sensory ganglion and of sympathetic trunk
      cervicothoracic ganglion].
AB  - The topographic pattern of neurons in spinal nerve sensory ganglion and of
      sympathetic trunk cervicothoracic ganglion was investigated at adult rats (n =
      12). Results of the work have shown, that these organs are characterized by a
      heterogeneity of the neurons according to their morphometric (Nissl's stain) and
      histochemical (acetylcholinestherase and NADPH-diaphorase activity) parameters.
      The common feature of ganglia organization was demonstrated by the clustered
      pattern of neuron topography. Clusters were formed on a principle of
      heterogeneity, uniting from 3-4 to 9-10 neurons. The application of a combined
      histochemical method has allowed to identify the histo-functional charactristics
      of neurons within the clusters of the ganglia studied, which were also detected
      by standard histological methods.

PMID- 21866803
TI  - [Contraction of the injured neuronal processes].
AB  - The investigation was performed on the isolated living neurons of a mollusk
      (Lymnaea stagnalis). The purpose of this study was to examine the contractile
      activity of the injured neuronal processes. Retraction of latter in Ringer's
      solution was found in 90% of the cases. The specific club-shaped structure
      (retraction bulb) served as a marker of contraction. The speed of process
      contraction fluctuated in different neurons from 0.03 to 9 microm/ min. As a
      result of usual linear contraction, the process diameter was increased on the
      average by 35%, while the cell body volume was increased on the average by 30%.
      The three forms of contractile activity were distinguished: linear contraction,
      isometric contraction (reduction of a process thickness with no change in its
      length) and mixed form of contraction. It is suggested that the mechanism of
      retraction takes part in the formation of diastasis after nerve sectioning and
      injury of the brain conducting pathways. Diastasis in the nerve is formed not
      only due to the elastic properties of its fibrous sheath and glia, but also as a
      result of nerve fiber retraction.

PMID- 21866804
TI  - [Dynamics of structural changes in the dorsal roots of spinal nerves in growing
      dogs].
AB  - Dorsal roots of spinal nerves (S1 segment) were studied in 9 growing mongrel dogs
      aged 2, 5 and 10 months using morphologic and morphomertric the methods.
      Longitudinal paraffin sections, impregnated with silver nitrate, and semithin
      transverse sections, stained with methylene blue-basic fuchsin, were used. The
      general regularities of structural organization, as well as the patterns of nerve
      fiber arrangement in the studied age periods have been determined. In the process
      of growth, the thickening of the dorsal roots was found (which was most
      pronounced until 5 months together with the increase of the diameter and the
      changes in the proportions of small, medium and large myelinated nerve fibers,
      the decrease of their number per unit section area.

PMID- 21866805
TI  - [Morphological characteristic of erythrocytes in experimental hypervitaminosis
      A].
AB  - This investigation was aimed at the analysis of the shape and morpho
      densitometric parameters of the erythrocytes in rats with experimental
      hypervitaminosis A. Male Wistar rats received 0.64 mg/g (1167 IU/g) of retinol
      palmitate (RP) in oil solution orally for 11 consecutive days. Rats fed oil alone
      and intact animals were used as control groups. At days 5 and 6 of the
      experiment, the first manifestations of hypervitaminosis A were observed (body
      mass loss, localized erythema and hemorrhages). In contrast to control groups, in
      rats with hypervitaminosis A, the area of erythrocyte cytoplasm decreased
      gradually in response to RP administration. Discocyte/spherocyte/stomatocyte
      ratio also changed dynamically: the proportion of discocytes progressively
      decreased, while the amount of spherocytes and stomatocytes increased. These
      results show that excess of the vitamin A alters the erythrocyte membrane
      structure. Integral optical density of erythrocyte cytoplasm in RP-treated rats
      as well as in oil-fed rats was lower than in intact animals. This may be an
      indirect evidence of the fall in erythrocyte hemoglobin content. The changes
      observed in erythrocytes of RP-treated rats may serve as an additional criterion
      for evaluation of hypervitaminosis A severity.

PMID- 21866806
TI  - [Individual peculiarities in the reaction of jejunum lymphoid structures in rats
      exposed to stress].
AB  - Using a complex of morphological methods, the peculiarities in the reaction of
      jejunum lymphoid structures were studied in 105 Wistar rats with reference to
      their behavioral characteristics (stress tolerance). Initially, in passive
      (stress prone) rats the number of lymphoid and plasma cells was higher than in
      active animals, together with the macrophage reaction, which may indicate greater
      activity of immune structures in this group of animals. In behaviorally active
      rats, the negative impact of stress was less pronounced; rehabilitation processes
      were faster, as compared to those in passive animals. By day 14 after the end of
      the experiment, the restoration of cell population of lymphocytes was observed in
      the wall of the intestine in the active animals, while in the passive rats, the
      processes of destruction of lymphocyte cell line was increased together with the
      macrophage response.

PMID- 21866807
TI  - [Structure of maxillary sinus mucous membrane under normal conditions and in
      odontogenic perforative sinusitis].
AB  - Methods of light, electron microscopy and immunohistochemistry were used to study
      the samples of maxillary sinus (MS) mucous membrane (MM) under normal conditions
      and in odontogenic sinusitis. To study the normal structure, the samples were
      obtained at autopsy from 26 human corpses 12-24 hours after death. Electron
      microscopic and immunohistochemical study was performed on biopsies of grossly
      morphologically unchanged MS MM, obtained during the operations for retention
      cysts in 6 patients. MS MM in perforative sinusitis was studied using the
      biopsies obtained from 43 patients. The material is broken into 4 groups
      depending on perforative sinusitis duration. Under normal conditions, MS MM is
      lined with a pseudostratified columnar ciliated epithelium. Degenerative changes
      of ciliated epithelial cells were already detected at short time intervals after
      MS perforations and become apparent due to reduction of specific volume of
      mitochondria and, rough endoplasmic reticulum, and increase of nuclear
      cytoplasmic ratio. In the globlet cells, the reduction of nuclear-cytoplasmic
      ratio was associated with the disturbance of the secretory product release. At
      time intervals exceeding 3 months, epithelium underwent metaplasia into simple
      cuboidal and stratified squamous keratinized, while in MS MM lamina propria,
      cellular infiltration was increased. CD4+ cell content in sinus MM gradually
      increased, while at late periods after perforation occurrence it decreased. Low
      CD4+ cell count within the epithelium and the absence of muromidase on the
      surface of MS MM was detected. With the increase of the time interval since MS
      perforation, the number of CD8+ and CD20+ cells in MS MM was found to increase.

PMID- 21866808
TI  - [Reactive changes of human gastric mucosa infected with Helicobacter pylori in
      the aspect of genetic characteristic of host inflammatory response].
AB  - The aim of this study was to determine the morphological changes of human gastric
      mucosa infected with Helicobacter pylori (HP) depending on polymorphism of the
      genes coding both interleukin-1beta and interleukin-1 receptor antagonist. 106
      juveniles with HP-induced chronic gastritis were studied along with 44 juveniles
      with gastritis, not associated with HP. In patients with HP-associated gastritis,
      the significant increase in epithelial proliferation and apoptosis indexes was
      observed. Epithelium proliferation zone was expanded in the direction of surface
      foveolar epithelium and into the depth of glands; pronounced lympho-plasma cell
      infiltration of mucosal lamina propria was observed. Cytokine gene polymorphisms
      were evaluated by PCR. The results suggest an association between more pronounced
      inflammation of gastric mucosa with the T allele of interleukin-1beta C -511 C >
      T gene polymorphous locus (Chi2 = 14.006; p = 0.001). No association was found of
      the interleukin-1beta C +3953 T gene and the variable number of tandem repeats in
      the 2nd introne of interleukin 1 receptor antagonist gene with morphological
      changes in the gastric mucosa.

PMID- 21866809
TI  - [Alcohol-induced changes of biogenic amine-containing structures of the large
      intestine].
AB  - Using the methods of luminescent microscopy and cytospectrofluorometry, biogenic
      amine-containing structures were studied in colon of rats subjected to alcohol
      intoxication of 2, 4 and 6 months' duration. It was demonstrated that 2- and 4
      month-long alcohol intoxication of animals resulted in biogenic amine content
      increase in the mucosal surface epithelium, submucosal mast cells and adrenergic
      nerve fibers within the connective tissue bands in the muscular tunic. At the
      same time, 6 month-long intoxication was accompanied by a stabilization of
      bioamine content at the elevated level.

PMID- 21866810
TI  - [The peculiarities of rat tissue reactions to intraperitoneal implants made out
      of biodegradable polyhydroxyalkanoates].
AB  - The reaction of rat tissues to intraperitoneal placement of implants made out of
      biodegradable polyhydroxyalkanoates (PHA), was studied at different time points
      after the operation by the methods of light microscopy. It was found that after
      intraperitoneal PHA implant placement, the active adhesive process started
      leading to formation of fibrous adhesions between PHA implants and intestinal
      loops. When PHA implants were used in the form of films, they became surrounded
      by a thick fibrous capsule. As a result of PHA implant placement in the form of
      ultrathin fibers, the extensive foreign body granulomas with perifocal
      inflammation and sclerosis of surrounding tissues were formed. In these
      granulomas the polymer fragmentation and phagocytosis by macrophages with
      formation of giant cells of foreign body occured. It is concluded that PHA
      implants are not biodegradable and induce tissue reactions similar to those
      caused by other foreign bodies.

PMID- 21866811
TI  - [Morphometric characteristic of the basilar part of occipital bone in different
      forms of the skull].
AB  - 140 preparations of the skull base and 97 preparations of the skull sagittal saw
      cuts were used to study the craniometric characteristics of the basilar part of
      the occipital bone. The dependence of craniometric characteristics on sex and
      form of the cerebral cranium was tested. Correlations between these parameters
      were determined. It was found that the occipital bone parameters studied have no
      significant sex differences, however the correlation was found between the width
      parameters of basilar part of occipital bone at the outer and inner cranial base.
      The data obtained should be taken into consideration during planning and
      fulfilling the transclival surgical procedures.

PMID- 21866812
TI  - [Morphogenesis of human placenta in the first trimester of gestation].
AB  - On the basis of morphometric and immunohistochemical study of placental villi
      obtained from 45 cases of medicinal and medical abortions in healthy women, the
      new data on placentation are presented with the discrimination of three stages of
      placental morphogenesis. The first stage (weeks 4 and 5 after fertilization)
      included a differentiation of villous chorion (chorion frondosum). It was
      characterized by high mitotic activity of villous cytotrophoblast and intensive
      vasculogenesis in the villous stroma. The second stage (weeks 6 and 7) included
      capillary development (angiogenesis) and formation of vascular communications
      within a "placenta-embryo" subsystem functioning in low-oxygen level environment.
      The third stage (weeks 8 and 9-10) was characterized by vascular bed formation in
      "mother-placenta" subsystem and by the beginning of more effective hemochorial
      embryo and fetal metabolism. As a result of placentation, hemodynamics formation
      in "mother-placenta-embryo" system was completed, which is a necessary condition
      for further fetal development.

PMID- 21866813
TI  - [Neural stem cell marker MSI-1 expression in rat telencephalon].
AB  - The aim of the study was to examine the distribution of cells expressing Msi-1
      (Musashi-1) protein which is believed to be a marker of neural stem cells, in rat
      telencephalon. These cells were found to be concentrated in the subventricular
      proliferative zone and diffusely scattered in striatum and hippocampus. Moreover,
      neurons with extensive Msi-1 reaction were found in habenular nuclei. The data
      obtained are not in full agreement with current views on the localization of
      neural stem cells in the brain.

PMID- 21866814
TI  - [Disperse endocrine system and APUD concept].
AB  - This review describes the problems of disperse endocrine system and APUD-system
      morphology, summarizes some debatable issues of single endocrine cell biology.
      The data presented refer to the history of both systems discovery, morphological
      methods of their study, developmental sources, their structural organization and
      physiological roles of their cells. The significance of single endocrine cells in
      the regulation of the organism functions is discussed.

PMID- 21866815
TI  - [Education of the elements of professional competence in the students in the
      process of teaching of operative surgery and topographic anatomy].

PMID- 21866816
TI  - [Topographic-anatomical terms as an integral part of International Anatomical
      Terminology].

PMID- 21866817
TI  - [Cone-beam tomography of congenital fissures of the alveolar process and palate].
AB  - Cone-beam tomography is one of the current radiodiagnostic techniques, which
      allows patients with congenital fissures of the alveolar process and soft and
      hard palates to be examined, by minimizing the radiation load. On surgical
      treatment planning, cone-beam tomography makes it possible to estimate the extent
      of a bone defect in the alveolar process, its sizes, the presence or absence of
      oronasal fistulas, the position of the intermaxilla, the state of bone tissue
      (sizes, density characteristics) in the genial area for an autograft, the degree
      of a maxillofacial deformity, and occlusive features. Postoperative cone-beam
      tomography permits one to estimate the degree of alveolar process recovery, the
      sizes of a regenerate, the processes of osteointegration, and the state of fixing
      elements and the donor bed.

PMID- 21866818
TI  - [Role of cone-beam tomography in choosing an endodontic treatment policy for
      adolescents and young people].
AB  - The everyday use of standard X-ray studies, such as intraoral radiography, less
      frequently orthopantomography, permits detailed characterization of the anatomic
      characteristics of dentin, which are required to plan an endodontic treatment
      policy for permanent teeth in adolescents and young people. The application of
      dental volume tomography (DVT) evidence will make it possible to objectify
      criteria for the level of formation of tooth root dentins and their
      mineralization levels, by further developing the principles of planning and
      endodontic treatment, which consider anatomic characteristics. The purpose of the
      investigation was to study the informative value of DVT during endodontic
      treatment for permanent teeth in adolescents and young people. One hundred and
      ninety-five DVT scans, 195 orthopantomograms, and 300 radio images, which were
      made in 159 patients aged 12 to 24 years (a study group) and 36 patients aged 25
      30 years (a control group), were examined. Analyzing DVT evidence yielded the
      mean threshold values for an apical foramen width of 0.62 to 0.66 mm and an
      apical root dentin density of 1390 to 1410 units, which were characteristic of
      formed permanent teeth. An endodontic treatment policy was chosen according to
      which range the values of apical foramen widths and dentin densities were within.
      The study of DTV values has indicated that this technique is of more informative
      value than others and may be recommended for its extensive use as a first-line
      method.

PMID- 21866819
TI  - [The specific features of coronary artery lesion in patients with signs of high
      cardiac risk in non-ST segment elevation acute coronary syndrome].
AB  - The paper covers risk stratification for cardiac events in patients with non-ST
      segment elevation acute coronary syndrome. It defines an association between risk
      factors, the specific features of coronary artery lesions, and the outcomes of
      the disease in relation to the used treatment policy. Particular emphasis is laid
      on the factors that are a handicap to the detection of a symptom-associated
      coronary artery in this category of patients.

PMID- 21866820
TI  - [Noninvasive radiodiagnosis of left ventricular diastolic dysfunction in
      hypertensive patients].
AB  - To define the informative value of Doppler studies in the early diagnosis of left
      ventricular (LV) diastolic dysfunction in patients with hypertensive disease
      (HD), the authors examined 74 patients with grade 1-2 HD, including 65 men and 9
      women aged 43 to 63 years. All the patients underwent echocardiography (echoCG),
      Doppler echoCG (DechoCG), tissue DechoCG (TDechoCG), and treadmill. According to
      the echoCG LV mass index (LVMI), all the patients were divided into 2 groups: 1)
      33 patients with increased LVMI and 2) 41 with normal LVMI. A control group
      consisted of 20 apparently healthy patients. Groups 1 and 2 showed a
      preponderance of patients with concentric LV hypertrophy (CLVH) and those with
      concentric LV remodeling, respectively. In accordance with DechoCG, the signs of
      primary LV diastolic dysfunction ((E/A = 0.8+/-0.1; IVRT = 103+/-15) were found
      only in Group 1 patients. TDechoCG displayed the signs of primary LV diastolic
      dysfunction in both groups (e'<a'; e'/a'<1). The E/e'ratio was significantly
      increased in Group 1i (p < 0.01). CONCLUSIONS: 1. DechoCG fails to reveal the
      initial signs of LV diastolic dysfunction. 2. The combined use of Doppler studies
      permits the initial signs of LV diastolic dysfunction to be detected in patients
      with HD. 3. In hypertensive disease patients with CLVH, as evidenced by echoCG,
      the higher E/e'> or =10 ratio, suggests elevated LV filling pressure as an early
      stage of diastolic dysfunction.

PMID- 21866821
TI  - [Improvement of ultrasound study in the diagnosis of pleurisies of various
      etiologies].
AB  - The study was undertaken to improve ultrasonography using needle biopsy under
      ultrasound control in the diagnosis of pleurisies of various etiologies. The
      patients of the Department of Thoracic Surgery, who had been divided by the
      nosological principle (nonspecific pleurisy, tuberculosis effusions, and tumorous
      and posttraumatic pleurisies), were followed up. The study and statistical
      processing yielded major ultrasound criteria for pleural effusions and a final
      diagnosis was made on the basis of needle biopsy under ultrasound control with
      subsequent morphological verification.

PMID- 21866822
TI  - [Shear wave elastography: possibilities of the differential diagnosis of focal
      and diffuse changes in various organs and tissues].
AB  - Ultrasound study (USS) using a shear wave elastography procedure was made in
      different groups of patients with morphologically verified focal and diffuse
      abnormalities of both superficial organs and structures and viscera. The
      qualitative and quantitative characteristics of the stiffness of normal and
      pathologic organs and tissues were estimated; there was a significance importance
      of differences in benign and malignant lesions. The magnitude of fibrous changes
      in the hepatic parenchyma was first estimated by a USS technique; there was
      evidence that there were significant differences in indicators in health and
      various liver abnormalities.

PMID- 21866823
TI  - [Radionuclide diagnosis of upper urinary tract patency in patients with cancer of
      the cervix uteri ].
AB  - The experience with dynamic renal scintigraphy has shown its high informative
      value and safety in evaluating the degree of intrarenal urine outflow disorders.
      However, failure to make an objective assessment of ureteral patency considerably
      limits its study. The set of studies, which is given in this paper, is devoted to
      precisely this, highly urgent, problem. The authors have developed an original
      procedure for diagnosing impaired urine outflow along the ureters during dynamic
      renal scintigraphy. The visual and digital characteristics of normal and impaired
      urine outflow in the supravesical segment are defined. The criteria
      characterizing severe impairments of renal urine derivation along the ureters are
      denoted. Risk factors for urine outflow disorders are identified in patients with
      cancer of the cervix uteri, who receive various treatment modalities.

PMID- 21866824
TI  - [Noninvasive magnetic resonance myelography in patients with lumbosacral
      intervertebral disk herniation].
AB  - For many decades X-ray myelography has remained one of the major diagnostic
      methods for spinal pathology. With the advent of computed tomography (CT), CT
      myelography using water-soluble contrast agents has been developed. Visualization
      of the subarachnoidal spaces of the spinal cord and dural sac without an
      intrathecal contrast agent has become possible with the emergence of magnetic
      resonance imaging (MRI). Its further development and improvement has brought to
      existence the new noninvasive technique MR myelography based on the suppression
      of a signal from the medulla and its enhancement from the cerebrospinal fluid
      containing spaces. This paper compares routine X-ray myelography, CT myelography,
      and MR myelography used in the diagnosis of lumbosacral intervertebral disk
      herniation and assesses the informative value and benefits of MR myelography as a
      noninvasive diagnostic method for this pathology.

PMID- 21866825
TI  - [X-ray densitometric characteristics of bone mineral density in patients with
      impaired biliation].
AB  - Dual-energy X-ray absorptiometry was used to examine 20 patients with obstructive
      jaundice, who had undergone external biliary drainage in the first surgical
      stage. A clinical comparison group comprised 34 patients without hepatobiliary
      diseases. Bone mineral density was measured in the lumbar spine, proximal femur,
      and ultradistal antibrachium. Impaired biliation was found to result in bone loss
      in the early-stage of the disease, which was more marked in the spongy bone. This
      allows the ultradistal antibrachium to be identified as a main observation area
      for dual-energy X-ray absorptiometry to make an early diagnosis of mineralization
      disorders. The integrated T index (Tint) calculated on the basis of the X-ray
      densitometry of a few skeletal portions may be used to obtain generalized
      information on bone mineral density.

PMID- 21866826
TI  - [Value of magnetic resonance imaging in the diagnosis of complicated forms of the
      diabetic foot].
AB  - Magnetic resonance imaging was performed in 98 patients to estimate the
      capabilities of radiodiagnosis in the study of complicated forms of the diabetic
      foot. This diagnostic technique can visualize foot changes with a high degree of
      validity.

PMID- 21866827
TI  - [Capabilities of ultrasound study and computed tomography in the diagnosis of
      circumscribed peritonitis in ureteral perforation].

PMID- 21866828
TI  - [Chest pain syndrome with normal coronary arteries: a diagnostic algorithm,
      causes, a role of multislice spiral computed tomography in the examination of
      these patients].

PMID- 21866829
TI  - [Genome damage and reactive oxygen species production in the progenies of
      irradiated CHO-K1 cells].
AB  - A series of experiments to study the delayed effects of gamma-radiation exposure
      in different generations of the progenies of the Chinese hamster ovary CHO-K1
      irradiated cells has been conducted. It has been shown that in the progenies of
      the cells irradiated with a dose of 1 Gy, the following effects are observed: in
      the 9-27 cell generations - increase in the genome damage, intracellular
      production of reactive oxygen species, apoptotic cells percentage and cell
      sensitivity to additional exposure (irradiation at a dose of 10 Gy); in the 30-42
      cell generations - decrease of the studied parameters up to control values and
      increased resistance to additional exposure. It is assumed that the decrease of
      the studied parameters up to the control values in the 30-42 postirradiation
      generations of cells is caused by elimination of damaged cells or transition of
      genomic instability into a hidden (latent) condition.

PMID- 21866830
TI  - [DNA damage in thymocytes of mice under combined acute whole body exposure to
      cadmium ions and gamma-radiation].
AB  - The effect of the combined acute whole body exposure to cadmium chloride (0.5 mg
      Cd2+ per kg body weight of animals) and gamma-radiation (1 Gy) on the DNA damage
      induction in thymocytes and thymic cellularity of mice was studied. It has been
      shown that CdCl2 solution injection 0.5 h before irradiation reduces the quantity
      of single-strand DNA breaks and alkali-labile sites in thymocytes 48 h after
      injection compared to gamma-radiation action only. The observed effect is
      accompanied by a sharp decrease of the thymic cellularity compared with the
      separate effects of both cadmium ions and irradiation, which masks the overall
      genotoxic effect of combined exposure and gives an illusion of cadmiumL ions
      radioprotective action. Cadmium chloride injection 24 h before irradiation leads
      to a significant additive increase in the single-strand DNA breaks and alkali
      labile sites number as compared to the separate effects of cadmium ions and
      irradiation alone. At the same time the decrease in the percentage of DNA tightly
      bound to proteins (DNA-protein cross-links) was noted in comparison with the
      action of gamma-radiation only. Statistically significant changes in thymic
      cellularity compared with separate effects of cadmium ions and irradiation were
      not found. Thus, our research has shown that under a combined action of cadmium
      ions and gamma-radiation on thymocytes in mice at the applied doses and exposure
      schemes the additive effects, rather than antagonism or radioprotective effects
      are observed.

PMID- 21866831
TI  - [SOS response of DNA repair and genetic cell instability under hypoxic
      conditions].
AB  - The SOS DNA repair pathway is induced in E. coli as a multifunctional cell
      response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or
      nalidixic acid treatment, thymine starvation, etc. Triggering of the system can
      be used as a general and early sign of DNA damage. Additionally, the SOS-response
      is known to be an "error-prone" DNA repair pathway and one of the sources of
      genetic instability. Hypoxic conditions are established to be the major factor of
      genetic instability as well. In this paper we for the first time studied the SOS
      DNA repair response under hypoxic conditions induced by the well known aerobic
      SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli
      PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide
      evidence that those agents were able to induce the SOS DNA repair response in E.
      coli at anaerobic growth conditions. The process does not depend on the
      transcriptional activity of the universal protein of E. col anaerobic growth Fnr
      [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in
      hypoxic conditions.

PMID- 21866832
TI  - [Effect of gamma-radiation on the activity of proteases associated with spleen
      and brain nuclear histones of young and old rats].
AB  - It has been found that proteases specifically splitting histones are associated
      with histones from spleen and brain nuclei of 4- and 26-month-old rats. The
      activity ofproteases isolated together with histones increases after irradiation
      of rats with 10 Gy The activation degree of these proteases depends on the animal
      age and postradiation period. Activation ofhistone-associated proteases by means
      of gamma-radiation is more pronounced in spleen nuclei from old rats than from
      the young ones. Irradiation of animals has been found to reduce histone H1 and
      core histone contents in the spleen and brain nuclei of both young and old rats.
      The radiation-induced proteolysis ofhistone H1 and core histones in spleen and
      brain nuclei leads to chromatin deconden-sation and DNA degradation by nucleases.
      The activity of histone-associated proteases is substantially higher in the
      nuclei of intensively proliferating spleen cells than in the brain nuclei. The
      experimental data indicate that histone-associated proteases participate in the
      regulation of DNA transcription, replication, and degradation.

PMID- 21866834
TI  - [Peculiarities of the ovary structure in the rat offspring developing under
      conditions of the removed thyroid gland of female rat with the thyroxine
      replacement therapy and external radiation exposure in utero].
AB  - The influence of a single external gamma-radiation at a dose of 1.0 Gy (dose rate
      9.08 x 10(-4) Gy/sec) on the 15th day of gestation in case of the removed complex
      of thyroid and parathyroid glands (thyroidparathyroidectomy) on the first day of
      gestation, as well as introduction of thyroxin and CaC12 on the structure of
      offspring ovary in postnatal ontogenesis (30-day old animals) was studied. It has
      been shown that thyroidparathyroidectomy of a female mother rat with thyroxine
      replacement therapy and irradiation, as well as the combination of these factors
      disturb the structure of ovarian tissues of the offspring. A single external
      irradiation on the 15th day of embryogenesis causes death of a considerable part
      of primordial follicles in the offspring ovary and growth of follicular layers in
      the secondary follicles. Thyroidparathyroidectomy of female rat on the first day
      of gestation with thyroxine replacement therapy causes delay in the development
      of follicles in the ovary at the early stages of maturation of 30-day old
      animals. The radiosensitivity of the ovarian tissues of the offspring that has
      been developed under the combined effect of the factors studied increases and
      results in an almost full loss of pool cells in the ovary of infant rats.

PMID- 21866833
TI  - [Effect of anabolic preparation fenobolin on blood, reproductive system and
      hormone levels in blood serum of fractionally irradiated male rats].
AB  - Influence of anabolic drug (phenobolin) injection at a dose of 2.5 mg/kg on some
      indexes of blood, reproductive system, the level of thyroid hormones,
      corticosterone and testosterone in blood serum of the male rats exposed to a
      fractional irradiation at the total dose of 2.0 Gy have been studied. A
      significant decrease in the quantity of leucocytes and lymphocytes after a
      fractional irradiation without and with phenobolin introduction was determined.
      Introduction of anabolic drug resulted in a significant drop of relative mass of
      testes and, particularly, epididymes, and also in a sharp decrease of the number
      of mature germ cells isolated from epididymes. A combined action of phenobolin
      and fractional irradiation (2.0 Gy) led to a significant reduction (3-5 times) in
      the quantity of mature germ cells in an epididymis. In some cases phenobolin
      influenced the level of testosterone in blood serum of the intact and irradiated
      animals. The anabolic steroid drug affects negatively the state of reproductive
      system of male rats.

PMID- 21866835
TI  - [Studies of physical and chemical properties of the vacuum UV-irradiated
      molecules of human hemoglobin and its components (heme and globin)].
AB  - The purpose of the present work is to study the vacuum ultraviolet radiation
      action on the optical and chromatographic characteristics of human hemoglobin
      molecules and their components - haem and globin. Using the methods of
      spectrophotometry and thin layer chromatography (TLC), we have investigated into
      the structural changes of molecules of human hemoglobin, haem and globin, induced
      by the influence of vacuum UV light (gamma = 118-134 nm, dose - 1.2 kJ/m2). It
      has been shown that vacuum ultraviolet radiation induces an infringement of the
      higher types of the spatial organization ofglobin molecules, thus leading to the
      changes in the structural state of the albuminous globule.

PMID- 21866836
TI  - [Mobile communication and health of population: estimation of danger, social and
      ethical problems].
AB  - Population lives under new electromagnetic conditions: constant round-the-clock
      compulsory chronic exposure of all groups of population to modulated wide
      spectrum of EMF RF during the work of base stations of mobile communication;
      daily and lifelong (from childhood) exposure of the brain to EMF RF of the mobile
      phone. Effects of exposure to EMF RF of low levels are presented. Results of
      research into chronic EMF RF exposure are absent. International recommendations
      and domestic guidelines do not take into account the changing conditions of EMF
      RF influence on the population: the brain has become a critical body, and
      children have been included in the risk group. Population actively continues to
      use mobile communication. In this situation estimation of the risks from mobile
      communication has become a social and ethical problem.

PMID- 21866837
TI  - [Change of cholinesterase relative activity under modulated ultra high frequency
      electromagnetic radiation in experiments in vitro].
AB  - Changes in the activity of enzyme cholinesterase (ChE) have been experimentally
      investigated under the influence of amplitude-modulated super-high-frequency
      electromagnetic radiation (carrier frequency of 2.375 MHz; power flux density of
      8 mW/cm2, 20 mW/cm2 and 50 mW/cm2; modulation frequency range 10 to 210 Hz;
      exposure time 5 min). The appearance of peaks of the cholinesterase increased
      relative activity, as well as the changes in the direction and intensity of the
      reaction associated with the modulation frequency and power flux are observed at
      equal power flux densities and exposure times.

PMID- 21866838
TI  - [Dependences of 137Cs and 90Sr concentration ratios in fish on the potassium and
      calcium concentrations in the freshwater reservoirs].
AB  - Activities of 137Cs and 90Sr, concentrations of the potassium and calcium ions in
      water and accumulation of the radionuclides in the organisms of various
      freshwater fish have been measured in the stagnant and semistagnant water
      reservoirs of Ukraine contaminated as a result of the Chernobyl accident. On the
      basis of the numerous experimental data for different regions the statistical
      parameters were derived describing the dependencies of the 137Cs and 90Sr
      concentration ratios in the muscle tissue of various fish species on the
      potassium and calcium concentrations in water, respectively.

PMID- 21866839
TI  - [The contribution of N.I. Pirogov to the development of forensic medicine (on the
      occasion of his 200th birthday anniversary)].
AB  - The main facets of professor N.I. Pirogov's professional activity are outlined.
      Forensic medicine (in the first place its organizational and practical aspects)
      was an integral component of his scientific and clinical work, along with applied
      anatomy and surgery. Landmark publications of N.I. Pirogov are listed with
      special reference to those concerned with forensic medical expertise of medical
      malpractice cases, postmortem inspection and intravital examination procedures,
      wound ballistics studies, the atlas of forensic pathology, etc. The surgeon and
      anatomist N.I. Pirogov can be justly regarded as a founder of forensic medicine
      in this country.

PMID- 21866840
TI  - [Forensic medical diagnostics of chronic alcoholic intoxication based on
      histological changes in the soft tissues of oral cavity and salivary glands].
AB  - Histological studies of oral cavity mucosa and salivary glands in subjects with
      chronic alcoholic intoxication revealed changes at the surface of the tongue and
      in the glandular tissues. Specific features of chronic alcoholic intoxication
      include acinar and ductal hyperplasia, reduction of the adipose tissue mass in
      salivary gland stroma, predominance of T-lymphocytes in hard palate minor
      salivary glands and B-lymphocytes in the stroma of labial minor salivary gland,
      the absence of plasma cells in the stroma of hard palate minor salivary glands
      and labial mucosa. Leukoplakia, dysplasia, and hyperplasia of the basal
      epithelial layer of oral cavity mucosa are considered to be the signs of long
      term (over 12 months) alcohol consumption.

PMID- 21866841
TI  - [Forensic medical evaluation of the severity of harm to the health in the cases
      of a fracture of the zygomaticoorbital complex complicated by ophthalmological
      disorders].
AB  - Expert reports of the cases of a fracture of the zygomaticoorbital complex are
      presented along with their comprehensive assessment based on the available
      investigative, clinical, and anamnestic data. The analysis included 71 patients,
      materials of forensic medical examination and other medical documentation, civil,
      criminal, and administrative proceedings. It was shown that forensic medical
      evaluation of the severity of harm to the health in the cases of a fracture of
      the zygomaticoorbital complex including those complicated by ophthalmological
      disorders is possible both in terms of the total duration of health impairment
      and in terms of the persistent loss of ability to work (on a percentage base). It
      is concluded that the degree of harm to the health in the cases of a fracture of
      the zygomaticoorbital complex complicated by ophthalmological disorders can be
      categorized as mild, moderate, and severe depending on the total duration of
      health impairment and percentage loss of ability to work. In case of irreparable
      facial disfigurement, the moderate harm to the health can be re-evaluated by the
      court as a severe one.

PMID- 21866842
TI  - [Morphometric diagnostics of the age of encapsulated subdural hematomas].
AB  - The present morphometric investigation was carried out using dura matter
      preparations, capsules, and contents of 94 encapsulated subdural hematomas
      obtained from the corpses of subjects with a non-penetrating craniocerebral
      injury and the duration of the post-traumatic period ranging from 8 days to 2.5
      years. The correlation analysis confirmed the necessity of differentiation
      between resorbed and unresorbed encapsulated subdural hematomas. The data
      obtained were used to construct 5 regression models for the estimation of the age
      of unresorbed encapsulated subdural hematomas and 1 regression model for the
      identification of the age of resorbed encapsulated subdural hematomas. The
      regression models included different combinations of three morphometric
      characteristics of the hematoma capsule as the independent variables, viz.
      maximum thickness, relative extent of hemosiderosis, and relative amount of
      macrophages in the cellular infiltrate. The amount of variability in the age of
      encapsulated subdural hematomas accounted for by the regression models is 62%. It
      is concluded that the results of the study can be used in the practical work of
      forensic medical experts.

PMID- 21866843
TI  - [Age-specific peculiarities of manifestations of a craniocerebral injury in
      children and adolescents with a combined blunt trauma].
AB  - This study was designed to estimate the frequency of head injuries and selected
      manifestations of craniocerebral traumas in children and adolescents with a fatal
      combined blunt trauma. It is included 289 cases of death from a combined blunt
      trauma (101 original observations and data of 188 archival documents). The
      victims were categorized into 3 age groups. One group was comprised of cases from
      0 to 3 years of life, group 2 included children aged from 4 to 11 years, and
      group 3 those at the age from 12 to 18 years. The age was shown to significantly
      influence both the frequency of head injuries and their severity. The maximum
      values of the two variables were recorded in the youngest age group. The
      frequency of head injuries and the number of selected manifestations of the
      craniocerebral trauma decreased with age.

PMID- 21866844
TI  - [Characteristic of injuries inflicted by a blank gunshot].
AB  - The analysis of the data published in the special literature indicates that
      forensic-medical aspects of the injuries inflicted by blank shots fired from a
      variety of small-arms weapons remain poorly known or virtually unexplored.
      Despite considerable variability of such injuries, their forensic-medical
      examination should include three basic components, viz. the proof of the absence
      of the injurious action of the shot, differential diagnostics of the consequences
      of injuries attributable to each traumatic factor of the shot, and experimental
      simulation of the damages to the human body and the clothes taking into account
      concrete models of the weapons and the blank cartridge.

PMID- 21866845
TI  - [Forensic medical assessment of injuries to the human body and clothes caused by
      a crossbow arrow].
AB  - Analysis of the data published in the special literature revealed the lack of
      information for the objective comprehensive forensic medical evaluation of
      injuries to the human body and clothes caused by the arrows from different models
      of crossbows. Morphological characteristics of injuries were shown to strongly
      depend on the design features of the arrows. This fact can be used to
      differentiate between injuries inflicted by crossbow arrows and other types of
      missile weapons.

PMID- 21866846
TI  - [On the importance of a comprehensive study for diagnostics of death from acute
      ethanol poisoning and coronary heart disease].
AB  - Over 30 000 cases of acute poisoning with ethyl alcohol and its surrogates are
      recorded annually in this country. Differential diagnostics between fatal
      poisoning and death from coronary heart disease encounters serious difficulties.
      The authors report a comprehensive forensic chemical, morphometric, and
      pathomorphological study of the activity of ethanol-oxidizing enzyme systems in
      the internal organs. The results of histochemical examination provide a basis for
      the extension of diagnostic potential of the available methods and the
      enhancement of the objective value of expert reports.

PMID- 21866847
TI  - [Forensic medical evaluation of stab-incised wounds caused by knives with point
      defects].
AB  - The present experimental study allowed to characterize specific signs of stab
      incised wounds caused by knives with operational point defects. Diagnostic
      coefficients calculated for these macro- and microscopic features facilitate
      differential diagnostics of the injuries and make it possible to identify a
      concrete stabbing/cutting weapon with which the wound was inflicted..

PMID- 21866848
TI  - [Characteristic of the damage caused to the clothes from woven fabric by a
      tiger's bite].
AB  - The tiger's teeth have been identified that may be of diagnostic value for the
      purpose of trace evidence analysis. The morphological features of the damage
      caused to the clothes from woven fabric by the tiger's bite are described. The
      knowledge of these features facilitates differential diagnostics between such
      damage and that inflicted by other blunt and sharp objects.

PMID- 21866849
TI  - [Correction of the alkylnitrite method for the detection of ethanol in blood
      taking into account toxico-kinetic and anthropometric data].
AB  - The correction coefficient for the systemic inaccuracy arising during
      determination of blood ethanol by alkylnitrite gas chromatography and concomitant
      calibration of aqueous solutions was estimated to equal 0.82; this finding was
      confirmed by the results of the toxico-kinetic assay for the measurement of total
      body water (TBW) from the kinetic curve characterizing the time dependence of
      ethanol concentration in the exhaled air, saliva, capillary and venous blood in
      combination with 4 anthropometric methods and (in several cases) direct physical
      detection of TBW. When detecting the blood ethanol level with a correction
      coefficient of 0.82, the mutual position of the kinetic curves for ethanol
      concentrations in the blood and the exhaled air (recalculated for the blood level
      with a coefficient of 2100) as well as in the blood and saliva agreed with that
      reported in the available literature; it significantly differed from the position
      of the curves obtained with a correction coefficient of 0.95. The causes
      accounting for the systematic inaccuracy and erroneous values of the correction
      coefficients in earlier studies are discussed.

PMID- 21866850
TI  - [The development of a method for chemico-toxicological analysis of trifluralin].

PMID- 21866851
TI  - [Forensic medical examination of a medical malpractice case as a form of
      situational expertise].
AB  - The authors propose to divide the process of forensic medical examination of a
      medical malpractice case into several stages and substantiate the possibility of
      their realization as a form of situational forensic medical expertise.

PMID- 21866852
TI  - [Peculiarities of forensic medical expertise in a situation of massive
      salmonellosis morbidity in a military unit].
AB  - The authors propose to consider infectious diseases as mass clinical conditions
      in both normative-legal and medical contexts. Peculiarities of commission and
      comprehensive inspections carried out in situations of massive infectious
      morbidity among servicemen are illustrated by examples of the work of state
      forensic medical organizations and investigative authorities of the Russian
      Defense Ministry.

PMID- 21866853
TI  - [Irreparable facial disfigurement].

PMID- 21866854
TI  - [Functional role of VNTR polymorphism of human genes].
AB  - A brief overview of the current views on the functional role of genetic VNTR
      polymorphism in humans is given. Data on the involvement of VNTRs in the
      regulation of gene expression and in the formation of complex phenotypes are
      presented. According to these data, the effects of VNTRs are determined by the
      number of repeats, the structure of their monomers and flanking haplotypes,
      epigenetic mechanisms (in the case of localization in imprinted regions) and can
      be modified by environmental factors. Some possible mechanisms of the influence
      of VNTRs on the level of expression are considered.

PMID- 21866855
TI  - [Genetic control of plant resistance to cold].
AB  - Data on the main pathways of the effect of cold on plants and on the pathways of
      plant responses to cold stress are reviewed. Genes involved in these processes
      are described. Special attention is given to transcription factors regulating
      expression of cold resistance genes. In addition, the participation of hormones
      and metabolites in the protection of plants from cold-induced damage is discussed
      and a relationship of the response to cold with the circadian rhythms and with
      the formation of stomata is demonstrated.

PMID- 21866856
TI  - [Genetic bases of diversity of the repertoire of immunoglobulins in application
      to diagnostics of clonality of B-cell lymphoid populations].
AB  - Molecular mechanisms underlying the formation of B-cell lymphomas in connection
      with processes associated with the maturation of B lymphocytes are reviewed. The
      currently used diagnostic methods do not always distinguish lymphomas from
      reactive changes of the lymphoid tissue. The principle of the molecular genetic
      method ofclonality detection in lymphocyte populations, technical problems, and
      the strategy of its application in clinical diagnostics of lymphomas are
      described in detail.

PMID- 21866857
TI  - [Chromatin decompaction in the interbands of Drosophila polytene chromosomes does
      not correlate with high transcription level].
AB  - The search for correlation between structural organization of particular
      chromosome regions and their functions is among key directions of molecular
      cytogenetics. In this study, we used polytene chromosomes of Drosophila
      melanogaster as a convenient model for examining transcriptional activity of
      chromomeres (bands) and interchromomeres (interbands) in eukaryotic interphase
      chromosomes. Using cloning of the interband DNA sequences and determination of
      the molecular limits for some interbands, we analyzed the transcriptional
      activity of these regions and compared the band and interband transcriptional
      activity in polytene chromosomes. Our results showed the absence of correlation
      between the decompacted state of the interbands examined and the levels of
      transcription observed in these regions.

PMID- 21866858
TI  - [A retroposition assay for the NLR1Cth from midge Chironomus thummi genome in the
      Chinese hamster ovary cells].
AB  - Non-Long Terminal Repeats (non-LTR or LINE) retrotransposons belong to the class
      of mobile genetic elements that are transposed into the host genome by reverse
      transcription of the RNA intermediate. Most of non-LTR retrotransposons contain
      two open reading frames (ORFs). The ORF1 codes for a gag-like protein, while the
      ORF2 codes for a reverse transcriptase (RT). We cloned two constructs based on
      Jockey-like non-LTR retrotransposon from genome Chironomus thummi (NLR1Cth). The
      retroposition assay performed in Chinese hamster ovary (CHO) cells demonstrated
      genome integrations of both constructs. The finding that the insect mobile
      element NLR1Cth is functional in mammalian cells demonstrates that this element
      possess universal enzymatic machinery allowing for active propagation in the
      genome of distant taxa. This suggests that the NLR1Cth transposon system may
      represent a useful tool for genetic analysis and manipulation in vertebrate
      cells.

PMID- 21866859
TI  - [Comparative cytogenetic analysis of hexaploid Avena L. species].
AB  - Using C-banding method and in situ hybridization with the 45S and 5S rRNA gene
      probes, six hexaploid species of the genus Avena L. with the ACD genome
      constitution were studied to reveal evolutionary karyotypic changes. Similarity
      in the C-banding patterns of chromosomal and in the patterns of distribution of
      the rRNA gene families suggests a common origin of all hexaploid species. Avena
      fatua is characterized by the broadest intraspecific variation of the karyotype;
      this species displays chromosomal variants typical of other hexaploid species of
      Avena. For instance, a translocation with the involvement of chromosome 5C
      marking A. occidentalis was discovered in many A. fatua accessions, whereas in
      other representatives of this species this chromosome is highly similar to the
      chromosome of A. sterilis. Only A. fatua and A. sativa show slight changes in the
      morphology and in the C-banding pattern of chromosome 2C. These results can be
      explained either by a hybrid origin of A. fatua or by the fact that this species
      is an intermediate evolutionary form of hexaploid oats. The 7C-17 translocation
      was identified in all studied accessions of wild and weedy species (A. sterilis,
      A. fatua, A. ludoviciana, and A. occidentalis) and in most A. sativa cultivars,
      but it was absent in A. byzantina and in two accessions of A. sativa. The origin
      and evolution of the Avena hexaploid species are discussed in context of the
      results.

PMID- 21866860
TI  - Genetic variation and clonal diversity of Bromus ircutensis Kom. in the Otingdag
      sandy land detected by ISSR markers.
AB  - Genetic variation and clonal diversity of nine populations of Bromus ircutensis
      Kom. from the Otingdag sandy land were investigated using Inter Simple Sequence
      Repeat (ISSR) markers. A total of 102 bands were amplified by using II ISSR
      primers chosen for the study. Among those 99% were polymorphic indicating high
      level of genetic variation at the species level with a mean genetic diversity (H)
      of 0.292 and Shannon information index (1) of 0.450. Percentage of polymorphic
      loci (PPL) of nine populations was 76.48% on average, which provides more
      evidence of considerable genetic variation at the population level. AMOVA
      analysis revealed that total genetic variation was higher within populations
      (87.06%) than between populations (12.94%), which is mainly the result of the
      extensive gene flow (Nm = 1.682) among B. ircutensis populations. UPGMA cluster
      analysis divided the nine populations into two groups. There was significant or
      moderate negative correlations between genetic diversity parameters (PPL, H, 1)
      and longitude or latitude. Mantel test also showed a significant correlation
      between geographical distance and genetic distance (r = 0.681, p = 0.002). Our
      findings indicated that distribution of B. ircutensis populations was influenced
      by geographical and ecological factors. Clonal diversity was also high with 108
      individuals identified by 11 ISSR primers being all of different genets. Our
      results provide a molecular basis for sustainable management and conservation
      ofB. ircutensis in the study area.

PMID- 21866861
TI  - [Phylogenetic relationships of Caucasian shrew Sorex satunini Ogn. (mammalia) in
      the superspecies Sorex araneus inferred from the data of karyological analysis
      and the mtDNA cyt b gene sequencing].
AB  - Using the data of karyological analysis, the phylogenetic relationships of
      Caucasian shrew Sorex satunini and the cryptic species of superspecies Sorer
      araneus were examined. In the population of Sorex satunini from the plain of
      North Ciscaucasia two deeply radiated cytochrome b genes (A and B) were
      identified. Genetic distance between haplotype A and B groups constituted 0.0675
      +/- 0.008, which is higher than any distance in superspecies S. araneus. Possible
      introgression of type B haplotypes from the populations of the evolutionary
      lineage S. subaraneus--S. araneus in Pleistocene and the time of the appearance
      of the chromosomal polymorphism of S. araneus is discussed. Our results show that
      the use of only one mitochondrial marker can lead to false conclusions on
      taxonomic diversity

PMID- 21866862
TI  - [Association of cattle growth hormone gene polymorphism with milk productivity].
AB  - Polymorphisms in two growth hormone (GH) gene regions, intron 3 (MspI
      polymorphism) and exon 4 (AluI polymorphism), and their association with milk
      productivity in Black Pied, Bestuzhevskaya, and Simmental cattle breeds have been
      studied. It was shown that allele GH(V) at the AluI polymorphic site and allele
      GH(D) at the MSPI polymorphic site of the GH gene, particularly in homozygous
      state, were more favorable in terms of agricultural importance than the GH(L) and
      GH(C) alleles.

PMID- 21866863
TI  - [Comparative estimation of the EGFP effects on the development of embryos
      obtained by reciprocal crossing of C57BL/6-Tgn(ACTbEGFP01Osb/J and C57BL/6 mice].
AB  - The effect of enhanced green fluorescent protein (EGFP) on the in vitro viability
      of early embryos of C57BL/6--Tgn(ACTbEGFP010sb/J mice has been studied. The
      number of viable ova in hemizygous females (-/egfp) has been shown to decrease.
      Irrespective of the EGFP level, it has no deleterious effect on the early
      development of embryos obtained by reciprocal crossing of hemizygous (-/egfp) and
      wild-type (-/-) mice.

PMID- 21866864
TI  - [Aneuploidy frequency in sperm of fertile men].
AB  - Analysis of sperm aneupoidy in 11 healthy men using two- or three-color FISH
      permitted to determine the average frequency of disomy in chromosomes 13 and 21
      (0.11% and 0.2%, respectively), disomy in chromosome 18 (0.05%) and reveal
      gonosomal aneuploidy variants and their frequency. The frequency of XX disomy was
      0.04%; XY, 0.17%; YY, 0.06%; and gonosomal nullisomy, 0.29%. We also assessed the
      frequency of meiotic nondisjunction of chromosomes 13, 21, 18, X, and Y and the
      frequency of XX, XY, and YY diploid chromosomes in sperm. The XY variant
      prevailed in gonosomal aneuploidy and diploidy and was associated with abnormal
      chromosomal segregation in meiotic anaphase I. The contribution of human sperm
      chromosomal imbalance to early embryonic lethality and to some chromosomal
      diseases of syndrome type in the offspring is discussed.

PMID- 21866865
TI  - [Morphological and genetic characteristics of leaf hairiness in wheat (Triticum
      aestivum L.) as analyzed by computer-aided phenotyping].
AB  - Computer-aided image processing was used to study the morphology of leaf
      hairiness in the wheat cultivars Saratovskaya 29 and Golubka, as well as the
      introgressed strain 102/00i of the cultivar Rodina carrying the hairiness control
      gene introgressed from Aegilops speltoides. Morphological differences in leaf
      hairiness were detected and described in detail. The genetic control ofhairiness
      was studied in two cultivars (Golubka and Saratovskaya 29) with similar hairiness
      patterns. Crossing these cultivars with the cultivar Rodina showed a monogenic
      inheritance in the cultivar Golubka and a digenic inheritance in the cultivar
      Saratovskaya 29, which has a denser hairiness. In the strain 102/00i and the
      cultivar Golubka, the number of trichomes was positively correlated with their
      mean length. The cultivar Golubka was used as an example to study the effect of
      environmental conditions on the formation of hairiness. Plants of these cultivars
      were found to form more but shorter trichomes.

PMID- 21866866
TI  - Gene diversity for haptoglobin and transferrin classical markers among Hindu and
      Muslim populations of Aligarh City, India.
AB  - The present paper reports the distribution of serum protein markers viz.
      haptoglobin and transferrin in two major groups of Aligarh city of North India.
      In present study we have undertaken a survey of 538 individuals belonging to
      eight different populations, four from the Hindu community i.e. Brahmin, Bania,
      Rajput and Jatav, and the rest four among the Muslim community i.e. Syed, Sheikh,
      Pathan and Ansari. The heterozygosity ranged from 0.2939 (Ansari) to 0.4873
      (Brahmin) for haptoglobin and from 0.000 (Rajput) to 0.1498 (Pathan) for
      transferrin. The values of D(ST) are 0.4122 and 0.4406, and that of G(ST) are
      0.5059 and 0.9726 for haptoglobin and transferrin markers respectively. Through
      F(ST) test, it has been concluded that there is a high genetic differentiation of
      populations within Hindu and Muslim groups, though there is absence of any
      significant differences between these groups.

PMID- 21866868
TI  - [Organ specificity of the genotoxic effects of cyclophosphane and dioxidine: an
      alkaline comet assay study].
AB  - The applicability of alkaline comet assay to studying the organ specificity of
      the genotoxic effects of drugs has been estimated using cells from four organs of
      mice (the liver, lungs, spleen, and brain). It has been found that
      cyclophosphamide damages DNA in all the four organs; and dioxidine, in all organs
      except the brain. It is concluded that this method can be used for studying the
      organ specificity of the DNA-damaging effects of various substances.

PMID- 21866867
TI  - [Polymorphic markers of some genes associated with multiple sclerosis in the
      population of Kazakhstan].
AB  - Associations of DR2 specificity of the DRB1gene and single-nucleotide
      polymorphisms of the tumor necrosis factor gene TNFalpha (-308 G/A), interleukin
      genes IL-beta (-511 C/T), IL-2 (-475 A/T and -631 G/A), IL-6(-634 C/G),
      paraoxanase gene PON1 (M55L, Q192R), and the mitochondrial protein transport gene
      UCP2 (-866 G/A) with the development of multiple sclerosis (MS) were studied in
      two main ethnic groups of Kazakhstan (Kazakhs and Russians). An association of
      DR2 specificity of the DRBI gene with MS was found in the combined group of
      Kazakhs, Russians, and offsprings from mixed marriages. No correlation between
      DR2 specificity and MS was found in the separately examined groups of Kazakhs and
      Russians. Statistically significant (p < 0.05) differences between the MS
      patients and healthy individuals were observed in the distribution of the
      genotypes at site -634 G/C of the IL-6 gene in the Kazakh group, in the allelic
      frequencies at site -308 A/G in the promoter region of the TNFalpha gene in the
      Russian group, and in the frequencies of alleles at the polymorphic Q 192R locus
      of the PON1 gene in the Kazakh group. No significant differences were revealed in
      the distribution of the genotypes and in the frequencies of alleles at the
      polymorphic sites of the genes IL-1beta (-511 C/T), IL-2 (-475 A/T and -631 G/A),
      PON1 (M55L), and UCP2 (-866 G/A).

PMID- 21866869
TI  - [Mutational analysis of the ribC gene of Bacillus subtilis].
AB  - The nucleotide sequence of the ribC gene encoding the synthesis ofbifunctional
      flavokinase/flavine adenine nucleotide (FAD) synthetase in Bacillus subtilis have
      been determined in a family of riboflavin-constitutive mutants. Two mutations
      have been found in the proximal region of the gene, which controls the
      transferase (FAD synthase) activity. Three point mutations and one double
      mutation have been found (in addition to the two mutations that were detected
      earlier) in the distal region of the gene, which controls the flavokinase (flavin
      mononucleotide (FMN) synthase) activity. On the basis of all data known to date,
      it has been concluded that the identified mutations affect riboflavin and ATP
      binding sites. No mutations have been found in the PTAN conserved sequence, which
      forms the magnesium and ATP common binding site and is identical for organisms of
      all organizational levels, from bacteria too humans.

PMID- 21866870
TI  - [How living organisms utilize super-active species: vitamin B12-dependent enzymes
      and their activity-maintaining systems].

PMID- 21866871
TI  - [Cysteinyl reukotriene receptors].

PMID- 21866872
TI  - [A novel chromatin-related factor that regulates the pluripotency of embryonic
      stem cells].

PMID- 21866873
TI  - [AP site recognition mechanism by the tryptophan residue in the vicinity of the
      catalytic center of AP endonucleases].

PMID- 21866874
TI  - [Metabolic machinery of sphingolipid signaling molecules].

PMID- 21866875
TI  - [Germline stem cells and sex differentiation in medaka (Oryzias latipes)].

PMID- 21866876
TI  - [Suppression of aquaporin 5 gene expression by endotoxin via cross-coupling of
      transcription factors].

PMID- 21866877
TI  - [Incomplete dominance in Mendelian laws and gene dosage].

PMID- 21866878
TI  - [Dark-operative protochlorophyllide reductase: structural framework common to
      nitrogenase and evolutionary aspects].

PMID- 21866879
TI  - [Function of sweet taste receptor in pancreatic beta-cells].

PMID- 21866880
TI  - The critical state of measurement in nursing education research.

PMID- 21866881
TI  - Use of film in teaching multiculturalism to future nurse educators.

PMID- 21866882
TI  - Influence of drying and storage on lipid and carotenoid stability of the
      microalga Phaeodactylum tricornutum.
AB  - The influence of short-term storage and spray- and freeze-drying of fresh
      microalgal paste on the stability of lipids and carotenoids of Phaeodactylum
      tricornutum was investigated. Furthermore, the effects of storage time (14 and 35
      days) and condition (vacuum packed vs non vacuum packed, -20  degrees C vs 4 
      degrees C vs 20  degrees C) after spray- and freeze-drying were studied. Total
      lipid content, free fatty acid content, carotenoid content and degree of lipid
      oxidation were measured. No effects of spray- and freeze-drying and subsequent
      storage were found on total lipid content, except for short-term storage of the
      fresh microalgal paste, which led to pronounced lipolysis and therefore a lower
      total lipid content. Freeze-dried microalgae were found to be more susceptible to
      lipolysis upon storage than spray-dried microalgae. On the other hand, spray
      dried microalgae were more susceptible to oxidation than freeze-dried microalgae,
      possibly due to breakdown of protecting carotenoids upon spray-drying. Hardly any
      effect of storage condition was observed for any of the parameters tested.

PMID- 21866883
TI  - New type of heterometallic 3d-4f rhomblike core in Weakley-like polyoxometalates.
AB  - The first heterometallic copper-cerium polyoxometalate,
      [{Ce(IV)(OAc)}Cu(II)(3)(H(2)O)(B-alpha-GeW(9)O(34))(2)](11-) (1), is composed of
      an unprecedented copper(II)-trisubstituted Weakley-type tungstogermanate subunit
      stabilized by coordination of a {Ce(OAc)}(3+) group at the vacant position. The
      title species contains a central {Ce(IV)Cu(II)(3)O(18)} rhomblike cluster that
      belongs to a new {(4f(ext))(3d(ext))(3d(int))(2)} type and magnetically behaves
      as a triangular Cu(3) system with overall antiferromagnetic exchange affected by
      the structural distortions the vicinity of diamagnetic Ce(IV) induces.

PMID- 21866884
TI  - Iododesilylation of TIPS-, TBDPS-, and TBS-substituted alkenes in connection with
      the synthesis of amphidinolides B/D.
AB  - The C-Si bonds of triisopropylsilyl-substituted alkenes, 1,3-dienes, and related
      multifunctional substrates, as well as analogous C-TBDPS and C-TBS bonds, are
      readily and chemoselectively cleaved with NIS (or other sources of I(+), such as
      N-iodosaccharin, 1,3-diodohydantoin, and Ipy(2)BF(4)). The desired iodoalkenes
      are obtained stereospecifically without byproducts, provided that the reactions
      are carried out in CF(3)CHOHCF(3) and, in general, with 30 mol % of Ag(2)CO(3)
      (or AgOAc/2,6-lutidine) as an additive. Fragment C10-C18 of cytotoxic
      amphidinolides B1-B3 and D has been synthesized using this improved procedure.

PMID- 21866885
TI  - Structural determinants of opioid and NOP receptor activity in derivatives of
      buprenorphine.
AB  - The unique pharmacological profile of buprenorphine has led to its considerable
      success as an analgesic and as a treatment agent for drug abuse. Activation of
      nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for
      certain aspects of buprenorphine's behavioral profile. In order to investigate
      the role of NOP activation further, a series of buprenorphine analogues has been
      synthesized with the aim of increasing affinity for the NOP receptor. Binding and
      functional assay data on these new compounds indicate that the area around C20 in
      the orvinols is key to NOP receptor activity, with several compounds displaying
      higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid
      receptor partial agonist of comparable efficacy to buprenorphine but with higher
      efficacy at NOP receptors.

PMID- 21866886
TI  - Active-site models for the nickel-iron hydrogenases: effects of ligands on
      reactivity and catalytic properties.
AB  - Described are new derivatives of the type [HNiFe(SR)(2)(diphosphine)(CO)(3)](+),
      which feature a Ni(diphosphine) group linked to a Fe(CO)(3) group by two bridging
      thiolate ligands. Previous work had described [HNiFe(pdt)(dppe)(CO)(3)](+)
      ([1H](+)) and its activity as a catalyst for the reduction of protons (J. Am.
      Chem. Soc. 2010, 132, 14877). Work described in this paper focuses on the effects
      on properties of NiFe model complexes of the diphosphine attached to nickel as
      well as the dithiolate bridge, 1,3-propanedithiolate (pdt) vs 1,2
      ethanedithiolate (edt). A new synthetic route to these Ni-Fe dithiolates is
      described, involving reaction of Ni(SR)(2)(diphosphine) with FeI(2)(CO)(4)
      followed by in situ reduction with cobaltocene. Evidence is presented that this
      route proceeds via a metastable MU-iodo derivative. Attempted isolation of such
      species led to the crystallization of NiFe(Me(2)pdt)(dppe)I(2), which features
      tetrahedral Fe(II) and square planar Ni(II) centers (H(2)Me(2)pdt = 2,2
      dimethylpropanedithiol). The new tricarbonyls prepared in this work are
      NiFe(pdt)(dcpe)(CO)(3) (2, dcpe = 1,2-bis(dicyclohexylphosphino)ethane),
      NiFe(edt)(dppe)(CO)(3) (3), and NiFe(edt)(dcpe)(CO)(3) (4). Attempted preparation
      of a phenylthiolate-bridged complex via the FeI(2)(CO)(4) + Ni(SPh)(2)(dppe)
      route gave the tetrametallic species [(CO)(2)Fe(SPh)(2)Ni(CO)](2)(MU-dppe)(2).
      Crystallographic analysis of the edt-dcpe compund [2H]BF(4) and the edt-dppe
      compound [3H]BF(4) verified their close resemblance. Each features pseudo
      octahedral Fe and square pyramidal Ni centers. Starting from [3H]BF(4) we
      prepared the PPh(3) derivative [HNiFe(edt)(dppe)(PPh(3))(CO)(2)]BF(4)
      ([5H]BF(4)), which was obtained as a ~2:1 mixture of unsymmetrical and
      symmetrical isomers. Acid-base measurements indicate that changing from Ni(dppe)
      (dppe = Ph(2)PCH(2)CH(2)PPh(2)) to Ni(dcpe) decreases the acidity of the cationic
      hydride complexes by 2.5 pK(a)(PhCN) units, from ~11 to ~13.5 (previous work
      showed that substitution at Fe leads to more dramatic effects). The redox
      potentials are more strongly affected by the change from dppe to dcpe, for
      example the [2](0/+) couple occurs at E(1/2) = -820 for [2](0/+) vs -574 mV (vs
      Fc(+/0)) for [1](0/+). Changes in the dithiolate do not affect the acidity or the
      reduction potentials of the hydrides. The acid-independent rate of reduction of
      CH(2)ClCO(2)H by [2H](+) is about 50 s(-1) (25  degrees C), twice that of
      [1H](+). The edt-dppe complex [2H](+) proved to be the most active catalyst, with
      an acid-independent rate of 300 s(-1).

PMID- 21866887
TI  - Cationic derivatives of dextran and hydroxypropylcellulose as novel potential
      heparin antagonists.
AB  - Cationic derivatives of dextran (Dex) and hydroxypropylcellulose (HPC) were
      studied as potential alternatives of protamine sulfate (PS) used in the reversal
      of anticoagulant activity of heparin. The modification was performed by the
      attachment of cationic groups to the Dex main chain or by grafting short side
      chains of a polycation onto HPC. The cationic derivatives of these
      polysaccharides were found to bind heparin with the efficiency increasing with
      growing degree of cationic modification. The degree of cationic modification and
      consequently the zeta potential of the polymers do not have to be high to achieve
      effective heparin binding. The size of the complexes of cationic Dex with
      unfractionated heparin (UFH) is a few micrometers. For complexes of cationic HPC
      and UFH the size is much below 1 MUm, both below and above the lower critical
      solution temperature of HPC. None of the cationic polysaccharides studied caused
      hemolysis. The concentrations of the polymers inducing the aggregation of human
      erythrocytes in vitro were determined.

PMID- 21866888
TI  - Rhodium-catalyzed olefin isomerization/enantioselective intramolecular Alder-ene
      reaction cascade.
AB  - The olefin isomerization/enantioselective intramolecular Alder-ene reaction
      cascade was achieved by using a cationic rhodium(I)/(R)-BINAP complex as a
      catalyst. A variety of substituted dihydrobenzofurans and dihydronaphthofurans
      were obtained from phenol- or naphthol-linked 1,7-enynes, respectively, with good
      yields and ee values.

PMID- 21866889
TI  - Relevance of emissions timing in biofuel greenhouse gases and climate impacts.
AB  - Employing life cycle greenhouse gas (GHG) emissions as a key performance metric
      in energy and environmental policy may underestimate actual climate change
      impacts. Emissions released early in the life cycle cause greater cumulative
      radiative forcing (CRF) over the next decades than later emissions. Some indicate
      that ignoring emissions timing in traditional biofuel GHG accounting
      overestimates the effectiveness of policies supporting corn ethanol by 10-90% due
      to early land use change (LUC) induced GHGs. We use an IPCC climate model to (1)
      estimate absolute CRF from U.S. corn ethanol and (2) quantify an emissions timing
      factor (ETF), which is masked in the traditional GHG accounting. In contrast to
      earlier analyses, ETF is only 2% (5%) over 100 (50) years of impacts. Emissions
      uncertainty itself (LUC, fuel production period) is 1-2 orders of magnitude
      higher, which dwarfs the timing effect. From a GHG accounting perspective,
      emissions timing adds little to our understanding of the climate impacts of
      biofuels. However, policy makers should recognize that ETF could significantly
      decrease corn ethanol's probability of meeting the 20% GHG reduction target in
      the 2007 Energy Independence and Security Act. The added uncertainty of
      potentially employing more complex emissions metrics is yet to be quantified.

PMID- 21866892
TI  - Bubble coalescence during acoustic cavitation in aqueous electrolyte solutions.
AB  - Bubble coalescence behavior in aqueous electrolyte (MgSO(4), NaCl, KCl, HCl,
      H(2)SO(4)) solutions exposed to an ultrasound field (213 kHz) has been examined.
      The extent of coalescence was found to be dependent on electrolyte type and
      concentration, and could be directly linked to the amount of solubilized gas (He,
      Ar, air) in solution for the conditions used. No evidence of specific ion effects
      in acoustic bubble coalescence was found. The results have been compared with
      several previous coalescence studies on bubbles in aqueous electrolyte and
      aliphatic alcohol solutions in the absence of an ultrasound field. It is
      concluded that the impedance of bubble coalescence by electrolytes observed in a
      number of studies is the result of dynamic processes involving several key steps.
      First, ions (or more likely, ion-pairs) are required to adsorb at the
      gas/solution interface, a process that takes longer than 0.5 ms and probably
      fractions of a second. At a sufficient interfacial loading (estimated to be less
      than 1-2% monolayer coverage) of the adsorbed species, the hydrodynamic boundary
      condition at the bubble/solution interface switches from tangentially mobile
      (with zero shear stress) to tangentially immobile, commensurate with that of a
      solid-liquid interface. This condition is the result of spatially nonuniform
      coverage of the surface by solute molecules and the ensuing generation of surface
      tension gradients. This change reduces the film drainage rate between interacting
      bubbles, thereby reducing the relative rate of bubble coalescence. We have
      identified this point of immobilization of tangential interfacial fluid flow with
      the "critical transition concentration" that has been widely observed for
      electrolytes and nonelectrolytes. We also present arguments to support the
      speculation that in aqueous electrolyte solutions the adsorbed surface species
      responsible for the immobilization of the interface is an ion-pair complex.

PMID- 21866890
TI  - Reverse fosmidomycin derivatives against the antimalarial drug target IspC (Dxr).
AB  - Reverse hydroxamate-based inhibitors of IspC, a key enzyme of the non-mevalonate
      pathway of isoprenoid biosynthesis and a validated antimalarial target, were
      synthesized and biologically evaluated. The binding mode of one derivative in
      complex with EcIspC and a divalent metal ion was clarified by X-ray analysis.
      Pilot experiments have demonstrated in vivo potential.

PMID- 21866893
TI  - Metabolic detoxication pathways for sterigmatocystin in primary tracheal
      epithelial cells: structural identification of glutathione adducts.

PMID- 21866894
TI  - Chemical behavior of electrochemically generated nanostructured silver surfaces.
AB  - A simple electrochemical method has been proposed for the preparation of silver
      nanoparticles that can be used for the detection of cyanide. Both the
      electrochemical behavior and morphology of the Ag nanoparticles have been
      characterized in the presence of KCN or diethyl cyanophosphonate (DECP) as well
      as in alkaline media. These were investigated by cyclic voltammetry and scanning
      electron microscopy (SEM). DECP is a simulant of the chemical warfare agent
      tabun.

PMID- 21866895
TI  - Structure and function relationship of murine insulin-like peptide 5 (INSL5):
      free C-terminus is essential for RXFP4 receptor binding and activation.
AB  - Insulin-like peptide 5 (INSL5) is a member of insulin/relaxin superfamily of
      peptides. It has recently been identified as the cognate ligand for the G-protein
      coupled receptor, RXFP4. Although the complete physiological role of this
      naturally occurring peptide is still under investigation, there is evidence that
      it acts to both stimulate appetite and activate colon motility. This suggests
      that both agonists and antagonists of the peptide may have potential therapeutic
      applications. To further investigate the physiological role of this peptide and
      because of the ready availability of the mouse as an experimental animal, the
      preparation of mouse INSL5 was undertaken. Because of its complex structure and
      the intractable nature of the two constituent chains, different solid phase
      synthesis strategies were investigated, including the use of a temporary B-chain
      solubilizing tag. Unfortunately, none provided significantly improved yield of
      purified mouse INSL5 which reflects the complexity of this peptide. In addition
      to the native peptide, two mouse INSL5 analogues were also prepared. One had its
      two chains as C-terminal amides, and the other contained a europium chelate
      monolabel for use in RXFP4 receptor assays. It was found that the INSL5 amide was
      substantially less potent than the native acid form. A similar observation was
      made for the human peptide acid and amide, highlighting the necessity for free C
      terminal carboxylates for function. Two additional human INSL5 analogues were
      prepared to further investigate the necessity of a free C-terminal. The results
      together provide a first insight into the mechanism whereby INSL5 binds to and
      activates RXFP4.

PMID- 21866896
TI  - Microcontact printing for creation of patterned lipid bilayers on tetraethylene
      glycol self-assembled monolayers.
AB  - Supported lipid bilayers (SLBs) formed on many different substrates have been
      widely used in the study of lipid bilayers. However, most SLBs suffer from
      inhomogeneities due to interactions between the lipid bilayer and the substrate.
      In order to avoid this problem, we have used microcontact printing to create
      patterned SLBs on top of ethylene-glycol-terminated self-assembled monolayers
      (SAMs). Glycol-terminated SAMs have previously been shown to resist absorbance of
      biomolecules including lipid vesicles. In our system, patterned lipid bilayer
      regions are separated by lipid monolayers, which form over the patterned
      hexadecanethiol portions of the surface. Furthermore, we demonstrate that alpha
      hemolysin, a large transmembrane protein, inserts preferentially into the lipid
      bilayer regions of the substrate.

PMID- 21866897
TI  - Breaking the proximal Fe(II)-N(His) bond in heme proteins through local
      structural tension: lessons from the heme b proteins nitrophorin 4, nitrophorin
      7, and related site-directed mutant proteins.
AB  - The factors leading to the breakage of the proximal iron-histidine bond in the
      ferroheme protein soluble guanylate cyclase (sGC) are still a matter of debate.
      This event is a key mechanism in the sensing of NO that leads to the production
      of the second-messenger molecule cGMP. Surprisingly, in the heme protein
      nitrophorin 7 (NP7), we noticed by UV-vis absorbance spectroscopy and resonance
      Raman spectroscopy that heme reduction leads to a loss of the proximal histidine
      coordination, which is not observed for the other isoproteins (NP1-4). Structural
      considerations led to the generation and spectroscopic investigation of site
      directed mutants NP7(E27V), NP7(E27Q), NP4(D70A), and NP2(V24E). Spectroscopic
      investigation of these proteins shows that the spatial arrangement of residues
      Glu27, Phe43, and His60 in the proximal heme pocket of NP7 is the reason for the
      weakened Fe(II)-His60 bond through steric demand. Spectroscopic investigation of
      the sample of NP7 reconstituted with 2,4-dimethyldeuterohemin ("symmetric heme")
      demonstrated that the heme vinyl substituents are also responsible. Whereas the
      breaking of the iron-histidine bond is rarely seen among unliganded ferroheme
      proteins, the breakage of the Fe(II)-His bond upon binding of NO to the sixth
      coordination site is sometimes observed because of the negative trans effect of
      NO. However, it is still rare among the heme proteins, which is in contrast to
      the case for trans liganded nitrosyl model hemes. Thus, the question of which
      factors determine the Fe(II)-His bond labilization in proteins arises.
      Surprisingly, mutant NP2(V24E) turned out to be particularly similar in behavior
      to sGC; i.e., the Fe(II)-His bond is sensitive to breakage upon NO binding,
      whereas the unliganded form binds the proximal His at neutral pH. To the best of
      our knowledge, NP2(V24E) is the first example in which the ability to use the His
      on <-> His-off switch was engineered into a heme protein by site-directed
      mutagenesis other than the proximal His itself. Steric tension is, therefore,
      introduced as a potential structural determinant for proximal Fe(II)-His bond
      breakage in heme proteins.

PMID- 21866898
TI  - Copper/H2O2-mediated oxidation of 2'-deoxyguanosine in the presence of 2-naphthol
      leads to the formation of two distinct isomeric adducts.
AB  - Exposure of cells to phenolic compounds through exogenous and endogenous sources
      can lead to deleterious effects via nucleobase modifications of DNA occurring
      under oxidative conditions. 2'-Deoxyguanosine (dG) is the most electron rich of
      the four canonical bases and includes many nucleophilic sites; it is also
      susceptible to oxidation with numerous reactive oxygen species. In these studies,
      dG was allowed to react with 2-naphthol in the presence of copper or iron salts
      yielding two principal isomeric products. Spectroscopic analysis and reactions
      with alkylated nucleosides support the assignment of compound 1a/1b as a pair of
      atropisomer N(2) adducts and compound 2a/2b as a diastereomeric mixture of
      tricyclic [4.3.3.0] adducts. Both products are the result of an overall four
      electron oxidation process and consequently have the same masses, though
      drastically different structures, providing mechanistic insight into their
      formation. Thus, dG alkylation by 2-naphthol under oxidative conditions yields
      products whose structural properties are altered, leading to potentially
      mutagenic effects in genomic DNA.

PMID- 21866899
TI  - Comparative evaluation of two structurally related flavonoids, isoliquiritigenin
      and liquiritigenin, for their oral infection therapeutic potential.
AB  - Isoliquiritigenin (1) and liquiritigenin (2) are structurally related flavonoids
      found in a variety of plants. The purpose of this study was to perform a
      comparative analysis of biological properties of these compounds in regard to
      their therapeutic potential for oral infections. Compound 1 demonstrated
      significant antibacterial activity against three major periodontopathogens,
      Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia. In
      contrast, 2 exerted less pronounced effects on the above bacterial species.
      Neither compound was effective against cariogenic bacteria (Streptococcus mutans
      and Streptococcus sobrinus). Furthermore, 1 exhibited a stronger inhibitory
      activity than 2 toward P. gingivalis collagenase and human matrix
      metalloproteinase 9. Finally, the capacity of 1 to attenuate the inflammatory
      response of macrophages induced by Aggregatibacter actinomycetemcomitans
      lipopolysaccharide (LPS) was much higher when compared to 2. The activation of
      transcriptional factors nuclear factor-kappaB (NF-kappaB) p65 and activator
      protein-1 (AP-1) associated with the LPS-induced inflammatory response in
      macrophages was inhibited strongly by 1, but less affected by 2.

PMID- 21866900
TI  - Bioactive dammarane-type saponins from Operculina turpethum.
AB  - Four new dammarane-type saponins, operculinosides A-D (1-4), were isolated from
      the aerial parts of Operculina turpethum, of which 1 and 2 are the first two
      dammarane-type triterpenoids having an oxymethyl group at C-24. Their structures
      were determined by spectroscopic analysis and acid hydrolysis. The absolute
      configuration of operculinoside A (1) was confirmed by X-ray crystallography.
      Compounds 1 and 3 showed significant protective activities against d
      galactosamine-induced toxicity in L-02 human hepatic cells.

PMID- 21866901
TI  - EPR, ENDOR, and DFT study of free radicals in L-lysine.HCl.2H2O single crystals X
      irradiated at 298 K.
AB  - With K-band EPR (Electron Paramagnetic Resonance), ENDOR (Electron-Nuclear DOuble
      Resonance), and EIE (ENDOR-induced EPR) techniques, three free radicals (RI-RIII)
      in L-lysine hydrochloride dihydrate single crystals X-irradiated at 298 K were
      detected at 298 K, and six radicals (R1, R1', R2-R5) were detected if the
      temperature was lowered to 66 K from 298 K. R1 and RI dominated the central
      portion of the EPR at 66 and 298 K, respectively, and were identified as main
      chain deamination radicals, (-)OOCCH(CH(2))(4)(NH(3))(+). R1' was identified as a
      main chain deamination radical with the different configuration from R1 at 66 K,
      and it probably formed during cooling the temperature from 298 to 66 K. The
      configurations of R1, R1', and RI were analyzed with their coupling tensors. R2
      and R3 each contain one alpha- and four beta-proton couplings and have very
      similar EIEs at three crystallographic axes. The two-layer ONIOM calculations (at
      B3LYP/6-31G(d,p):PM3) support that R2 and R3 are from different radicals:
      dehydrogenation at C4, (-)OOCCH(NH(3))(+)CH(2)CH(CH(2))(2)(NH(3))(+), and
      dehydrogenation at C5, (-)OOCCH(NH(3))(+)(CH(2))(2)CHCH(2)(NH(3))(+),
      respectively. The comparisons of the coupling tensors indicated that R2 (66 K) is
      the same radical as RII (298 K), and R3 is the same as RIII. Thus, RII and RIII
      also are the radicals of C4 and C5 dehydrogenation. R4 and R5 are minority
      radicals and were observed only when temperature was lowered to 66 K. R4 and R5
      were only tentatively assigned as the side chain deamination radical, (-)OOCCH
      (NH(3))(+)(CH(2))(3)CH(2), and the radical dehydrogenation at C3, (
      )OOCCH(NH(3))(+)CH(CH(2))(3)(NH(3))(+), respectively, although the evidence was
      indirect. From simulation of the EPR (B//a, 66 K), the concentrations of R1, R1',
      and R2-R5 were estimated as: R1, 50%; R1', 11%; R2, 14%; R3, 16%; R4, 6%; R5, 3%.

PMID- 21866902
TI  - Deuterium enrichment of interstellar methanol explained by atom tunneling.
AB  - We calculate, down to low temperature and for different isotopes, the reaction
      rate constants for the hydrogen abstraction reaction H + H(3)COH -> H(2) +
      CH(2)OH/CH(3)O. These explain the known abundances of deuterated forms of
      methanol in interstellar clouds, where CH(2)DOH can be almost as abundant as
      CH(3)OH. For abstraction from both the C- and the O-end of methanol, the barrier
      crossing motion involves the movement of light hydrogen atoms. Consequently,
      tunneling plays a dominant role already at relatively high temperature. Our
      implementation of harmonic quantum transition state theory with on the fly
      calculation of forces and energies accounts for these tunneling effects. The
      results are in good agreement with previous semiclassical and quantum dynamics
      calculations (down to 200 K) and experimental studies (down to 295 K). Here we
      extend the rate calculations down to lower temperature: 30 K for abstraction from
      the C-end of methanol and 80 K for abstraction from the OH-group. At all
      temperatures, abstraction from the C-end is preferred over abstraction from the O
      end, more strongly so at lower temperature. Furthermore, the tunneling behavior
      strongly affects the kinetic isotope effects (KIEs). D + H(3)COH -> HD + CH(2)OH
      has a lower vibrationally adiabatic barrier than H + H(3)COH -> H(2) + CH(2)OH,
      giving rise to an inverse KIE (k(H)/k(D) < 1) at high temperature, in accordance
      with previous experiments and calculations. However, since tunneling is more
      facile for the light H atom, abstraction by H is favored over abstraction by D
      below ~135 K, with a KIE k(H)/k(D) of 11.2 at 30 K. The H + D(3)COD -> HD +
      CD(2)OD reaction is calculated to be much slower than the D + H(3)COH -> HD +
      CH(2)OH, in agreement with low-temperature solid-state experiments, which
      suggests the preference for H (as opposed to D) abstraction from the C-end of
      methanol to be the mechanism by which interstellar methanol is deuterium
      enriched.

PMID- 21866903
TI  - Redox-responsive nanoparticles from the single disulfide bond-bridged block
      copolymer as drug carriers for overcoming multidrug resistance in cancer cells.
AB  - Multidrug resistance (MDR) is a major impediment to the success of cancer
      chemotherapy. The intracellular accumulation of drug and the intracellular
      release of drug molecules from the carrier could be the most important barriers
      for nanoscale carriers in overcoming MDR. We demonstrated that the redox
      responsive micellar nanodrug carrier assembled from the single disulfide bond
      bridged block polymer of poly(epsilon-caprolactone) and poly(ethyl ethylene
      phosphate) (PCL-SS-PEEP) achieved more drug accumulation and retention in MDR
      cancer cells. Such drug carrier rapidly released the incorporated doxorubicin
      (DOX) in response to the intracellular reductive environment. It therefore
      significantly enhanced the cytotoxicity of DOX to MDR cancer cells. It was
      demonstrated that nanoparticular drug carrier with either poly(ethylene glycol)
      or poly(ethyl ethylene phosphate) (PEEP) shell increased the influx but decreased
      the efflux of DOX by the multidrug resistant MCF-7/ADR breast cancer cells, in
      comparison with the direct incubation of MCF-7/ADR cells with DOX, which led to
      high cellular retention of DOX. Nevertheless, nanoparticles bearing PEEP shell
      exhibited higher affinity to the cancer cells. The shell detachment of the PCL-SS
      PEEP nanoparticles caused by the reduction of intracellular glutathione
      significantly accelerated the drug release in MCF-7/ADR cells, demonstrated by
      the flow cytometric analyses, which was beneficial to the entry of DOX into the
      nuclei of MCF-7/ADR cells. It therefore enhanced the efficiency in overcoming MDR
      of cancer cells, which renders the redox-responsive nanoparticles promising in
      cancer therapy.

PMID- 21866905
TI  - Microscopic calculations of Hugoniot curves of neat triaminotrinitrobenzene
      (TATB) and of its detonation products.
AB  - We compute the Hugoniot curves of both neat triaminotrinitrobenzene (TATB) and
      its detonation products mixture using atomistic simulation tools. To compute the
      Hugoniot states, we adapted our sampling constraints in average (SCA) method
      (Maillet et al. Appl. Math. Res. eXpress 2009, 2008, abn004) to Monte Carlo
      simulations. For neat TATB, we show that the potential proposed by Rai (Rai et
      al. J. Chem. Phys. 2008, 129, 194510) is not accurate enough to predict the
      Hugoniot curve and requires some optimization of its parameters. Concerning the
      detonation products, thermodynamic properties at chemical equilibrium are
      computed using a specific reaction ensemble Monte Carlo (RxMC) method (Bourasseau
      et al. Phys. Chem. Chem. Phys. 2011, 13, 7060), taking into account the presence
      of carbon clusters in the fluid mixture. We show that this explicit description
      of the solid phase immersed in the fluid phase modifies the chemical equilibrium.

PMID- 21866904
TI  - Triazole-containing isothiazolidine 1,1-dioxide library synthesis: one-pot, multi
      component protocols for small molecular probe discovery.
AB  - The construction of two libraries of triazole-containing isothiazolidine 1,1
      dioxides is reported utilizing either a one-pot click/aza-Michael or click/OACC
      esterification protocol. One core dihydroisothiazole 1,1-dioxide scaffold was
      prepared rapidly on multigram scale via ring-closing metathesis (RCM) and was
      subjected to a one-pot multicomponent click/aza-Michael protocol with an array of
      amines and azides for the generation of a 180-member triazole-containing
      isothiazolidine 1,1-dioxide library. Alternatively, three daughter scaffolds were
      generated via the aza-Michael of three amino alcohols, followed by a one-pot,
      multicomponent click/esterification protocol utilizing a ring-opening metathesis
      polymerization (ROMP)-derived coupling reagent, oligomeric alkyl carbodiimide
      (OACC) to generate a 41-member library of triazole-containing isothiazole 1,1
      dioxides.

PMID- 21866907
TI  - Design of colored multilayered electrophoretic particles for electronic inks.
AB  - The preparation of multilayered latex particles with surface functional groups
      suitable for use as electrophoretic particles in electronic inks has been
      studied. The particles are formed by dispersion polymerization and have a
      polystyrene core, slightly cross-linked with divinylbenzene (DVB), and a
      poly(methyl methacrylate) (PMMA) or a poly(acrylic acid) (PAA) shell. After
      grafting alkyl chains on their surface, the particles are negatively or
      positively charged and sterically stabilized against aggregation in nonpolar
      solvent. The particles were dyed by incorporation of Nigrosin during
      polymerization or by swelling in supercritical CO(2) in the presence of a dye.
      Particle size, morphology, incorporated dye content and zeta potential were
      determined. A dual-particle electronic ink based on a mixture of the colored
      multilayered particles and white hybrid TiO(2)-polymer particles was prepared and
      electro-optically tested.

PMID- 21866906
TI  - Oligomeric state of the oxalate transporter, OxlT.
AB  - OxlT, the oxalate transporter of Oxalobacter formigenes, was studied to determine
      its oligomeric state in solution and in the membrane. Three independent
      approaches were used. First, we used triple-detector (SEC-LS) size exclusion
      chromatography to analyze purified OxlT in detergent/lipid micelles. These
      measurements evaluate protein mass in a manner independent of contributions from
      detergent and lipid; such work shows an average OxlT mass near 47 kDa for
      detergent-solubilized material, consistent with that expected for monomeric OxlT
      (46 kDa). A disulfide-linked OxlT mutant was used to verify that it was possible
      detect dimers under these conditions. A second approach used amino-reactive cross
      linkers of varying spacer lengths to study OxlT in detergent/lipid micelles and
      in natural or artificial membranes, followed by analysis via sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. These tests, performed under
      conditions where the presence of dimers can be documented for either of two known
      dimeric transporters (AdiC or TetL), indicate that OxlT exists as a monomer in
      the membrane and retains this status upon detergent solubilization. In a final
      test, we showed that reconstitution of OxlT into lipid vesicles at variable
      protein/lipid ratios has no effect on the specific activity of subsequent oxalate
      transport, as the OxlT content varies between 0.027 and 5.4 OxlT
      monomers/proteoliposome. We conclude that OxlT is a functional monomer in the
      membrane and in detergent/lipid micelles.

PMID- 21866908
TI  - Volumetric characterization of interactions of glycine betaine with protein
      groups.
AB  - We report the partial molar volumes and adiabatic compressibilities of N-acetyl
      amino acid amides and oligoglycines at glycine betaine (GB) concentrations
      ranging from 0 to 4 M. We use these results to evaluate the volumetric
      contributions of amino acid side chains and the glycyl unit (-CH(2)CONH-) as a
      function of GB concentration. We analyze the resulting GB dependences within the
      framework of a statistical thermodynamic model and evaluate the equilibrium
      constant for the reaction in which a GB molecule binds each of the
      functionalities under study replacing four water molecules. We calculate the free
      energy of the transfer of functional groups from water to concentrated GB
      solutions, DeltaG(tr), as the sum of a change in the free energy of cavity
      formation, DeltaDeltaG(C), and the differential free energy of solute-solvent
      interactions, DeltaDeltaG(I), in a concentrated GB solution and water. Our
      results suggest that the transfer free energy, DeltaG(tr), results from a fine
      balance between the large DeltaDeltaG(C) and DeltaDeltaG(I) contributions. The
      range of the magnitudes and the shape of the GB dependence of DeltaG(tr) depend
      on the identity of a specific solute group. The interplay between DeltaDeltaG(C)
      and DeltaDeltaG(I) results in pronounced maxima in the GB dependences of
      DeltaG(tr) for the Val, Leu, Ile, Trp, Tyr, and Gln side chains as well as the
      glycyl unit. This observation is in qualitative agreement with the experimental
      maxima in the T(M)-versus-GB concentration plots reported for ribonuclease A and
      lysozyme.

PMID- 21866909
TI  - Synthesis of antimitotic thioglycosides: in vitro and in vivo evaluation of their
      anticancer activity.
AB  - The synthesis and biological activity of oleylN-acetyl-alpha- and beta-d
      glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4,
      respectively) are reported. The compounds exhibited antimitotic activity on rat
      glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar
      range. Analysis of cell extracts using ultra performance liquid chromatography
      mass spectrometry showed that the synthetic glycosides produce alterations in
      glycosphingolipid metabolism, with variable effect on the level of
      glucosylceramide depending on the configuration of the antimitotic used. In vivo
      experiments in nude mice bearing an implanted C6 glioma showed that the alpha
      thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was
      inactive, highlighting the importance of using enzyme resistant glycosides.

PMID- 21866911
TI  - Thin gold film-assisted fluorescence spectroscopy for biomolecule sensing.
AB  - We present a configuration for fluorescence spectroscopy that exploits the
      optical properties of semitransparent gold films and widely available
      instrumentation. This method enables monitoring of biomolecule interactions with
      small molecules tethered on substrates in multicomponent environments. The
      neurotransmitter serotonin (5-hydroxytryptamine) was covalently attached to self
      assembled monolayers on thin gold films at low density to facilitate antibody
      recognition. Protein-binding studies were performed in a fluorescently labeled
      immunoassay format. We find that the use of this method enables evaluation of
      nonspecific binding and relative quantification of specific binding between
      competing binding partners. This fluorescence spectroscopy technique has the
      potential to assess biosensor or medical device responses in complex biological
      matrices.

PMID- 21866910
TI  - N'-(arylsulfonyl)pyrazoline-1-carboxamidines as novel, neutral 5
      hydroxytryptamine 6 receptor (5-HT6R) antagonists with unique structural
      features.
AB  - The 5-HT(6) receptor (5-HT(6)R) has been in the spotlight for several years
      regarding CNS-related diseases. We set out to discover novel, neutral 5-HT(6)R
      antagonists to improve off-target selectivity compared to basic amine-containing
      scaffolds dominating the field. High-throughput screening identified the N'
      (sulfonyl)pyrazoline-1-carboxamidine scaffold as a promising neutral core for
      starting hit-to-lead. Medicinal chemistry, molecular modeling, small molecule NMR
      and X-ray crystallography were subsequently applied to optimize the leads into
      antagonists (compounds 1-49) displaying high 5-HT(6)R affinity with optimal off
      target selectivity. Unique structural features include a pseudoaromatic system
      and an internal hydrogen bond freezing the bioactive conformation. While
      physicochemical properties and CNS availability were generally favorable,
      significant efforts had to be made to improve metabolic stability. The optimized
      structure 42 is an extremely selective, hERG-free, high-affinity 5-HT(6)R
      antagonist showing good human in vitro metabolic stability. Rat pharmacokinetic
      data were sufficiently good to enable further in vivo profiling.

PMID- 21866912
TI  - Highly NIR-emissive lanthanide polyselenides.
AB  - Ln(SePh)(3) (Ln = Ce, Pr, Nd), prepared by reduction of PhSeSePh with elemental
      Ln and Hg catalyst, reacts with excess elemental Se to give
      (py)(11)Ln(7)Se(21)HgSePh, an ellipsoidal polyselenide cluster. The molecular
      structure contains two square arrays of eight- or nine-coordinate Ln fused at one
      edge to form a V shape that is also capped on the concave side by a centrally
      located nine-coordinate (Se(3))pyLn(Se(3)) and on the convex side by a 2-fold
      disordered SeHgSePh. The central Ln coordinates to selenido, triselenido, and
      pyridine ligands, while all other Ln coordinate to selenido, diselenido,
      triselenido, and pyridine ligands. Thermal treatment of the Pr compound at 650 
      degrees C gave Pr(2)Se(3) and Pr(3)Se(4). NIR emission studies of the Nd compound
      show four transitions from the excited-state (4)F(3/2) ion to (4)I(9/2),
      (4)I(11/2), (4)I(13/2), and (4)I(15/2) states. The (4)F(3/2) ion to (4)I(11/2)
      transition (1075 nm emission) exhibited 43% quantum efficiency. This is the
      highest quantum efficiency reported for a 'molecular' Nd compound and leads a
      group of selenide-based clusters that has shown extraordinary quantum efficiency.
      In terms of efficiency and concentration, these compounds compare favorably with
      solid-state materials.

PMID- 21866913
TI  - Understanding the electronic structure of 4d metal complexes: from molecular
      spinors to L-edge spectra of a di-Ru catalyst.
AB  - L(2,3)-edge X-ray absorption spectroscopy (XAS) has demonstrated unique
      capabilities for the analysis of the electronic structure of di-Ru complexes such
      as the blue dimer cis,cis-[Ru(III)(2)O(H(2)O)(2)(bpy)(4)](4+) water oxidation
      catalyst. Spectra of the blue dimer and the monomeric [Ru(NH(3))(6)](3+) model
      complex show considerably different splitting of the Ru L(2,3) absorption edge,
      which reflects changes in the relative energies of the Ru 4d orbitals caused by
      hybridization with a bridging ligand and spin-orbit coupling effects. To aid the
      interpretation of spectroscopic data, we developed a new approach, which computes
      L(2,3)-edges XAS spectra as dipole transitions between molecular spinors of 4d
      transition metal complexes. This allows for careful inclusion of the spin-orbit
      coupling effects and the hybridization of the Ru 4d and ligand orbitals. The
      obtained theoretical Ru L(2,3)-edge spectra are in close agreement with
      experiment. Critically, existing single-electron methods (FEFF, FDMNES) broadly
      used to simulate XAS could not reproduce the experimental Ru L-edge spectra for
      the [Ru(NH(3))(6)](3+) model complex nor for the blue dimer, while charge
      transfer multiplet (CTM) calculations were not applicable due to the complexity
      and low symmetry of the blue dimer water oxidation catalyst. We demonstrated that
      L-edge spectroscopy is informative for analysis of bridging metal complexes. The
      developed computational approach enhances L-edge spectroscopy as a tool for
      analysis of the electronic structures of complexes, materials, catalysts, and
      reactive intermediates with 4d transition metals.

PMID- 21866914
TI  - Iodine-catalyzed amination of benzoxazoles: a metal-free route to 2
      aminobenzoxazoles under mild conditions.
AB  - A facile metal-free route of oxidative amination of benzoxazole by activation of
      C-H bonds with secondary or primary amines in the presence of catalytic iodine in
      aqueous tert-butyl hydroperoxide proceeds smoothly at ambient temperature under
      neat reaction condition to furnish the high yield of the aminated product. This
      user-friendly method to form C-N bonds produces tertiary butanol and water as the
      byproduct, which are environmentally benign. The application of the methodology
      is demonstrated by synthesizing therapeutically active benzoxazoles.

PMID- 21866915
TI  - Trolox, a water-soluble analogue of alpha-tocopherol, photoprotects the surface
      exposed regions of the photosystem II reaction center in vitro. Is this
      physiologically relevant?
AB  - Can Trolox, a water-soluble analogue of alpha-tocopherol and a scavenger of
      singlet oxygen ((1)O(2)), provide photoprotection, under high irradiance, to the
      isolated photosystem II (PSII) reaction center (RC)? To answer the question, we
      studied the endogenous production of (1)O(2) in preparations of the five
      chlorophyll PSII RC (RC5) containing only one beta-carotene molecule. The
      temporal profile of (1)O(2) emission at 1270 nm photogenerated by RC5 in D(2)O
      followed the expected biexponential behavior, with a rise time, unaffected by
      Trolox, of 13 +/- 1 MUs and decay times of 54 +/- 2 MUs (without Trolox) and 38
      +/- 2 MUs (in the presence of 25 MUM Trolox). The ratio between the total (k(t))
      and chemical (k(r)) bimolecular rate constants for the scavenging of (1)O(2) by
      Trolox in aqueous buffer was calculated to be ~1.3, with a k(t) of (2.4 +/- 0.2)
      * 10(8) M(-1) s(-1) and a k(r) of (1.8 +/- 0.2) * 10(8) M(-1) s(-1), indicating
      that most of the (1)O(2) photosensitized by methylene blue chemically reacts with
      Trolox in the assay buffer. The photoinduced oxygen consumption in the oxygen
      electrode, when RC5 and Trolox were mixed, revealed that Trolox was a better
      (1)O(2) scavenger than histidine and furfuryl alcohol at low concentrations
      (i.e., <1 mM). After its incorporation into detergent micelles in unbuffered
      solutions, Trolox was able to photoprotect the surface-exposed regions of the D1
      D2 heterodimer, but not the RC5 pigments, which were oxidized, together with the
      membrane region of the protein matrix of the PSII RC, by (1)O(2). These results
      are discussed and compared with those of studies dealing with the physiological
      role of tocopherol molecules as a (1)O(2) scavenger in thylakoid membranes of
      photosynthetic organisms.

PMID- 21866916
TI  - Synthesis of PDE IVb inhibitors. 1. Asymmetric synthesis and stereochemical
      assignment of (+)- and (-)-7-[3-(cyclopentyloxy)-4-methoxyphenyl]hexahydro-3H
      pyrrolizin-3-one.
AB  - Asymmetric synthesis of GlaxoSmithKline's highly potent phosphodiesterase
      inhibitor 1 has been accomplished in nine steps and 16% overall yield. The
      original strategy suggested involves as a key step the silylation of enantiopure
      six-membered cyclic nitronates 4 obtained by a highly stereoselective [4 + 2]
      cycloaddition of an appropriate nitroalkene 5 to trans-1-phenyl-2
      (vinyloxy)cyclohexane. Functionalization of the resulting 5,6-dihydro-4H-1,2
      oxazine and subsequent stereoselective reduction of 1,2-oxazine ring in
      intermediate 2 furnished the pyrrolizidinone framework with the recovery of
      chiral auxiliary alcohol.

PMID- 21866917
TI  - Multifunctional picoliter droplet manipulation platform and its application in
      single cell analysis.
AB  - We developed an automated and multifunctional microfluidic platform based on
      DropLab to perform flexible generation and complex manipulations of picoliter
      scale droplets. Multiple manipulations including precise droplet generation,
      sequential reagent merging, and multistep solid-phase extraction for picoliter
      scale droplets could be achieved in the present platform. The system precision in
      generating picoliter-scale droplets was significantly improved by minimizing the
      thermo-induced fluctuation of flow rate. A novel droplet fusion technique based
      on the difference of droplet interfacial tensions was developed without the need
      of special microchannel networks or external devices. It enabled sequential
      addition of reagents to droplets on demand for multistep reactions. We also
      developed an effective picoliter-scale droplet splitting technique with magnetic
      actuation. The difficulty in phase separation of magnetic beads from picoliter
      scale droplets due to the high interfacial tension was overcome using
      ferromagnetic particles to carry the magnetic beads to pass through the phase
      interface. With this technique, multistep solid-phase extraction was achieved
      among picoliter-scale droplets. The present platform had the ability to perform
      complex multistep manipulations to picoliter-scale droplets, which is
      particularly required for single cell analysis. Its utility and potentials in
      single cell analysis were preliminarily demonstrated in achieving high-efficiency
      single-cell encapsulation, enzyme activity assay at the single cell level, and
      especially, single cell DNA purification based on solid-phase extraction.

PMID- 21866918
TI  - Miniemulsion synthesis of metal-oxo cluster containing copolymer nanobeads.
AB  - Hybrid nanobeads containing either a manganese-oxo or manganese-iron-oxo cluster
      have been prepared via the miniemulsion polymerization technique. Two new ligand
      substituted oxo clusters, Mn(12)O(12)(VBA)(16)(H(2)O)(4) and
      Mn(8)Fe(4)O(12)(VBA)(16)(H(2)O)(4) (where VBA = 4-vinylbenzoate), have been
      prepared and characterized. Polymerization of the functionalized metal-oxo
      clusters with styrene under miniemulsion conditions produced monodispersed
      polymer nanoparticles as small as ~60 nm in diameter. The metal-oxo polymer
      nanobeads were fully characterized in terms of synthetic parameters, composition,
      structure, and magnetic properties.

PMID- 21866919
TI  - Study of the chemical composition and antimicrobial activities of ethanolic
      extracts from roots of Scutellaria baicalensis Georgi.
AB  - Scutellaria baicalensis  Georgi (SBG), commonly named Huangqin, showed strong in
      vitro antimicrobial effects. However, limited research is available to
      systematically evaluate the effects of extraction methods on the phytochemical
      composition of SBG and its associated antimicrobial effects. In addition, limited
      studies have tested SBG as a natural antimicrobial agent on fresh produce such as
      tomatoes. In the current study, powered roots of SBG were extracted with 60, 80,
      and 100% ethanol, and their antiviral and antibacterial activities were
      evaluated. SBG ethanol extracts (SBGEEs) at 6.25 mg/mL showed limited antiviral
      activities against coliphage MS2 and hepatitis A virus. The SBG 80% ethanol
      extract (SBG80%EE) exhibited the lowest minimum inhibitory concentrations (MIC)
      and minimum bactericidal concentrations (MBC) against six foodborne pathogens.
      SBG80%EE had the highest contents of flavonoids and phenolic acids determined by
      high-performance liquid chromatography (HPLC). Among these bioactive compounds,
      ferulic acid had the lowest MIC and MBC values, 0.4 and 1.0 mg/mL, respectively,
      followed by baicalein and baicalin. Washing with SBG80%EE (12.5 mg/mL) resulted
      in >1 log reduction of  Salmonella enterica  serovars Typhimurium, Kentucky,
      Senftenberg, and Enteritidis on surface-inoculated grape tomatoes. None of SBGEE
      solutions changed the total phenolic content, color, or pH values of grape
      tomatoes. The quantification of these antimicrobial flavonoids and phenolic acids
      is important to maintain the quality and antimicrobial efficacy of SBG extracts.
      In addition, the application of SBG on tomatoes has provided valuable insights on
      the potential usage of this antimicrobial extract.

PMID- 21866920
TI  - Trivalent actinide and lanthanide separations by tetradentate nitrogen ligands: a
      quantum chemistry study.
AB  - Although a variety of tetradentate ligands, 6,6'-bis(5,6-dialkyl-1,2,4-triazin-3
      yl)-2,2'-bipyridines (BTBPs), have been proved as effective ligands for selective
      extraction of Am(III) over Eu(III) experimentally, the origin of their
      selectivity is still an open question. To elucidate this question, the geometric
      and electronic structures of the actinide and lanthanide complexes with the BTBPs
      have been investigated systematically by using relativistic quantum chemistry
      calculations. We show herein that in 1:1 (metal:ligand) type complexes
      substitution of electron-donating groups to the BTBP molecule can enhance its
      coordination ability and thus the energetic stability of the formed Am(III) and
      Eu(III) complexes in the gas phase. According to our results, Eu(III) can
      coordinate to the BTBPs with higher stability in energy than Am(III), no matter
      whether there are nitrate ions in the inner-sphere complexes. The presence of
      nitrate ions leads to formation of the probable Am(III) and Eu(III) complexes,
      M(NO(3))(3)(H(2)O)(n) (M = Am, Eu), in nitric acid solutions. It has been found
      that the changes of Gibbs free energy play an important role for Am(III)/Eu(III)
      separation. In fact, the weaker complexing ability of Am(III) with nitrate ions
      and water molecules makes the decomposition of Am(NO(3))(3)(H(2)O)(4) more
      favorable in energy, which may thus increase the possibility of formation of
      Am(BTBPs)(NO(3))(3). Our work may shed light on the design of novel extractants
      for Am(III)/Eu(III) separation.

PMID- 21866922
TI  - Chitosan nanogels by template chemical cross-linking in polyion complex micelle
      nanoreactors.
AB  - Chitosan covalent nanogels cross-linked with genipin were prepared by template
      chemical cross-linking of chitosan in polyion complex micelle (PIC) nanoreactors.
      By using this method, we were able to prepare chitosan nanogels using only
      biocompatible materials without organic solvents. PIC were prepared by
      interaction between chitosan (X(n) = 23, 44, and 130) and block copolymer
      poly(ethylene oxide)-block-poly[sodium 2-(acrylamido)-2-methylpropanesulfonate]
      (PEO-b-PAMPS) synthesized by single-electron transfer-living radical
      polymerization (SET-LRP). PIC with small size (diameter about 50 nm) and low
      polydispersity were obtained up to 5 mg/mL. After cross-linking of chitosan with
      genipin, the nanoreactors were dissociated by adding NaCl. The dissociation of
      the nanoreactors and the formation of the nanogels were confirmed by (1)H NMR,
      DLS, and TEM. The size of the smallest nanogels was about 50 nm in the swollen
      state and 20 nm in the dry state. The amount of genipin used during reticulation
      was an important parameter to modulate the size of the nanogels in solution.

PMID- 21866921
TI  - Toward eradicating HIV reservoirs in the brain: inhibiting P-glycoprotein at the
      blood-brain barrier with prodrug abacavir dimers.
AB  - Eradication of HIV reservoirs in the brain necessitates penetration of antiviral
      agents across the blood-brain barrier (BBB), a process limited by drug efflux
      proteins such as P-glycoprotein (P-gp) at the membrane of brain capillary
      endothelial cells. We present an innovative chemical strategy toward the goal of
      therapeutic brain penetration of the P-gp substrate and antiviral agent abacavir,
      in conjunction with a traceless tether. Dimeric prodrugs of abacavir were
      designed to have two functions: inhibit P-gp efflux at the BBB and revert to
      monomeric therapeutic within cellular reducing environments. The prodrug dimers
      are potent P-gp inhibitors in cell culture and in a brain capillary model of the
      BBB. Significantly, these agents demonstrate anti-HIV activity in two T-cell
      based HIV assays, a result that is linked to cellular reversion of the prodrug to
      abacavir. This strategy represents a platform technology that may be applied to
      other therapies with limited brain penetration due to P-glycoprotein.

PMID- 21866923
TI  - Construction of carbocyclic ring of indoles using ruthenium-catalyzed ring
      closing olefin metathesis.
AB  - The selective synthesis of substituted indoles was achieved by the ring-closing
      olefin metathesis (RCM)/elimination sequence or the RCM/tautomerization sequence
      of functionalized pyrrole precursors. The RCM/elimination sequence was also
      applied to double ring closure to yield a substituted carbazole.

PMID- 21866924
TI  - Synthesis of amino-1,4-benzoquinones and their use in Diels-Alder approaches to
      the aminonaphthoquinone antibiotics.
AB  - A new protocol for the synthesis of protected amino-1,4-benzoquinones by
      oxidation of the corresponding 2,5-dimethoxyaniline derivatives using PhI(OAc)(2)
      or PhI(OCOCF(3))(2) in water containing 2.5% methanol is reported. The process
      represents an improvement over previously reported methods, both in terms of
      yield and number of steps, and in the range of nitrogen protecting groups that it
      tolerates. A number of novel aminobenzoquinones were prepared and subsequently
      used as dienophiles in Diels-Alder reactions to form building blocks for the
      synthesis of the aminonaphthoquinone antibiotics such as salinisporamycin.

PMID- 21866925
TI  - Synthesis of (-)-alpha-kainic acid via TMSCl-promoted Pd-catalyzed zinc-ene
      cyclization of an allyl acetate.
AB  - A highly practical synthesis of enantiopure (-)-alpha-kainic acid is accomplished
      in 37% overall yield, using 13 linear steps and a minimum of chromatographic
      separations via an unprecedented TMSCl-promoted palladium-catalyzed zinc-ene
      cyclization of an allyl acetate.

PMID- 21866926
TI  - DABCO-bis(sulfur dioxide), DABSO, as a convenient source of sulfur dioxide for
      organic synthesis: utility in sulfonamide and sulfamide preparation.
AB  - The charge-transfer complex generated from the combination of DABCO and sulfur
      dioxide, DABSO, is a bench-stable colorless solid suitable for use in organic
      synthesis as a replacement for gaseous sulfur dioxide. The complex can be
      combined with Grignard reagents to form sulfinates, which can then be converted
      in situ to a series of sulfonamides. Alternatively, reaction with anilines and
      iodine leads to the formation of a series of sulfamides. Cheletropic addition
      between DABSO and 2,3-dimethylbutadiene provides the corresponding sulfolene.

PMID- 21866927
TI  - Microcontact printing of monodiamond nanoparticles: an effective route to
      patterned diamond structure fabrication.
AB  - By combining microcontact printing with a nanodiamond seeding technique, a
      precise micrometer-sized chemical vapor deposition (CVD) diamond pattern have
      been obtained. On the basis of the guidance of basic theoretical calculations,
      monodisperse detonation nanodiamonds (DNDs) were chosen as an "ink" material and
      oxidized poly(dimethylsiloxane) (PDMS) was selected to serve as a stamp because
      it features a higher interaction energy with the DNDs compared to that of the
      original PDMS. The adsorption kinetics shows an approximately exponential law
      with a maximum surface DND density of 3.4 * 10(10) cm(-2) after 20 min. To
      achieve a high transfer ratio of DNDs from the PDMS stamp to a silicon surface, a
      thin layer of poly(methyl methacrylate) (PMMA) was spin coated onto the
      substrates. A microwave plasma chemical vapor deposition system was used to
      synthesize the CVD diamond on the seeded substrate areas. Precise diamond
      patterns with a low expansion ratio (3.6%) were successfully prepared after 1.5 h
      of deposition. Further increases in the deposition time typically lead to a high
      expansion rate (~0.8 MUm/h). The general pattern shape, however, did not show any
      significant change. Compared with conventional diamond pattern deposition
      methods, the technique described here offers the advantages of being simple,
      inexpensive, damage-free, and highly compatible, rendering it attractive for a
      broad variety of industrial applications.

PMID- 21866928
TI  - Two-photon optical properties of near-infrared dyes at 1.55 MUm excitation.
AB  - Two-photon (2P) optical properties of cyanine dyes were evaluated using a 2P
      fluorescence spectrophotometer with 1.55 MUm excitation. We report the 2P
      characteristics of common NIR polymethine dyes, including their 2P action cross
      sections and the 2P excited fluorescence lifetime. One of the dyes, DTTC, showed
      the highest 2P action cross-section (~103 +/- 19 GM) and relatively high 2P
      excited fluorescence lifetime and can be used as a scaffold for the synthesis of
      2P molecular imaging probes. The 2P action cross-section of DTTC and the lifetime
      were also highly sensitive to the solvent polarity, providing other additional
      parameters for its use in optical imaging and the mechanism for probing
      environmental factors. Overall, this study demonstrated the quantitative
      measurement of 2P properties of NIR dyes and established the foundation for
      designing molecular probes for 2P imaging applications in the NIR region.

PMID- 21866929
TI  - Gold(I)-catalyzed tandem cyclization-selective migration reaction of 1,3-dien-5
      ynes: regioselective synthesis of highly substituted benzenes.
AB  - Highly substituted benzene derivatives have been easily prepared in a
      regioselective way from readily available 1,3-hexadien-5-ynes through a gold(I)
      catalyzed tandem reaction. The process involves an initial cyclization followed
      by a selective Wagner-Meerwein shift in which the migration preference seems to
      be determined by the ability to stabilize a positive charge.

PMID- 21866930
TI  - Polyfluorinated compounds: past, present, and future.
AB  - Interest and concern about polyfluorinated compounds (PFCs), such as
      perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and an
      increasing number of other related compounds is growing as more is learned about
      these ubiquitous anthropogenic substances. Many of these compounds can be toxic,
      and they are regularly found in the blood of animals and humans worldwide. A
      great deal of research has been conducted in this area, but a surprising amount
      remains unknown about their distribution in the environment and how people
      ultimately become exposed. The utility of these compounds seems to ensure their
      continued use in one form or another for the foreseeable future, presenting a
      long-term challenge to scientists, industry leaders, and public health officials
      worldwide.

PMID- 21866933
TI  - Nanoparticle size is a critical physicochemical determinant of the human blood
      plasma corona: a comprehensive quantitative proteomic analysis.
AB  - In biological fluids, proteins associate with nanoparticles, leading to a protein
      "corona" defining the biological identity of the particle. However, a
      comprehensive knowledge of particle-guided protein fingerprints and their
      dependence on nanomaterial properties is incomplete. We studied the long-lived
      ("hard") blood plasma derived corona on monodispersed amorphous silica
      nanoparticles differing in size (20, 30, and 100 nm). Employing label-free liquid
      chromatography mass spectrometry, one- and two-dimensional gel electrophoresis,
      and immunoblotting the composition of the protein corona was analyzed not only
      qualitatively but also quantitatively. Detected proteins were bioinformatically
      classified according to their physicochemical and biological properties. Binding
      of the 125 identified proteins did not simply reflect their relative abundance in
      the plasma but revealed an enrichment of specific lipoproteins as well as
      proteins involved in coagulation and the complement pathway. In contrast,
      immunoglobulins and acute phase response proteins displayed a lower affinity for
      the particles. Protein decoration of the negatively charged particles did not
      correlate with protein size or charge, demonstrating that electrostatic effects
      alone are not the major driving force regulating the nanoparticle-protein
      interaction. Remarkably, even differences in particle size of only 10 nm
      significantly determined the nanoparticle corona, although no clear correlation
      with particle surface volume, protein size, or charge was evident. Particle size
      quantitatively influenced the particle's decoration with 37% of all identified
      proteins, including (patho)biologically relevant candidates. We demonstrate the
      complexity of the plasma corona and its still unresolved physicochemical
      regulation, which need to be considered in nanobioscience in the future.

PMID- 21866931
TI  - Small-molecule control of protein degradation using split adaptors.
AB  - Targeted intracellular degradation provides a method to study the biological
      function of proteins and has numerous applications in biotechnology. One
      promising approach uses adaptor proteins to target substrates with genetically
      encoded degradation tags for proteolysis. Here, we describe an engineered split
      adaptor system, in which adaptor assembly and delivery of substrates to the ClpXP
      protease depends on a small molecule (rapamycin). This degradation system does
      not require modification of endogenous proteases, functions robustly over a wide
      range of adaptor concentrations, and does not require new synthesis of adaptors
      or proteases to initiate degradation. We demonstrate the efficacy of this system
      in E. coli by degrading tagged variants of LacI repressor and FtsA, an essential
      cell-division protein. In the latter case, addition of rapamycin causes
      pronounced filamentation because daughter cells cannot divide. Strikingly,
      washing rapamycin away reverses this phenotype. Our system is highly modular,
      with clearly defined interfaces for substrate binding, protease binding, and
      adaptor assembly, providing a clear path to extend this system to other
      degradation tags, proteases, or induction systems. Together, these new reagents
      should be useful in controlling protein degradation in bacteria.

PMID- 21866934
TI  - Clickable enzyme-linked immunosorbent assay.
AB  - Click chemistry is explored as a potential cost-effective and selective
      immobilization method for the production of an enzyme-linked immunosorbent assay
      (ELISA). Coatings were formulated containing either a terminal alkyne or a
      bicyclo[6.1.0]non-4-yne (BCN) chemical handle, and a diagnostic peptide was
      subsequently immobilized onto these coatings by the copper-catalyzed azide-alkyne
      1,3-dipolar cycloaddition (CuAAC) or copper-free strain-promoted azide-alkyne 1,3
      dipolar cycloaddition (SPAAC), respectively. The terminal alkyne-containing
      coating showed high background levels in subsequent ELISA's due to the copper
      catalyst used in the immobilization step. The BCN-containing coating, however,
      was successfully employed and presents a cost-effective alternative to existing
      (strept)avidin-biotin immobilization methods. This technology was illustrated
      with an ELISA used for the diagnosis of rheumatoid arthritis (RA) but could be
      easily applied to a wide range of diagnostic tests.

PMID- 21866935
TI  - Semishells: versatile plasmonic nanoparticles.
AB  - Localized surface plasmon excitations in metal nanostructures have a strong
      impact on light scattering, absorption, and local field intensities at the
      nanoscale. Tweaking the nanoparticle shape, size, and material enables
      researchers to engineer the resonance wavelength position, the nanoparticles'
      local field enhancement, and their scattering properties. In particular, by
      breaking the symmetry of originally symmetric nanostructures, additional degrees
      of freedom can be explored. One particular example of a highly investigated
      nanostructure is the so-called semishell (or nanocup or nanocrescent moon). In
      this issue of ACS Nano, King et al. report on the angular and spectral scattering
      properties of plasmonic semishells and the effect of a high-index substrate on
      these properties.

PMID- 21866937
TI  - Large spontaneous polarization and clear hysteresis loop of a room-temperature
      hybrid ferroelectric based on mixed-halide [BiI3Cl2] polar chains and
      methylviologen dication.
AB  - The search for hybrid organic-inorganic materials, which have the great advantage
      that they can be synthesized at moderate temperature (T < 200  degrees C),
      remains a great challenge in the field of ferroelectrics. Here, a room
      temperature ferroelectric material with interesting characteristics,
      (MV)[BiI(3)Cl(2)] (MV(2+) = methylviologen), is reported. Its structure is based
      on polar inorganic chains resulting from a remarkable Cl/I segregation induced by
      methylviologen entities, which coincide with the fourfold polar axis of the
      tetragonal structure. Of great importance is that this room-temperature hybrid
      ferroelectric displays a clear electrical hysteresis loop with a large
      spontaneous polarization (>15 MUC.cm(-2)).

PMID- 21866938
TI  - Comparative analysis of hazardous air pollutant emissions of casting materials
      measured in analytical pyrolysis and conventional metal pouring emission tests.
AB  - Demonstration-scale metal pouring emission tests and bench-scale Curie-point
      pyrolysis emission tests were conducted to identify and quantify the hazardous
      air pollutant (HAP) emissions of five kinds of casting materials, namely,
      bituminous coal, cellulose, conventional phenolic urethane binder (PUB),
      naphthalene-depleted PUB, and a collagen-based binder. For a given casting
      material, the major HAP species generated in Curie-point pyrolysis were
      essentially the same as those generated in demonstration-scale metal pouring. The
      8-10 HAP species identified in the Curie-point pyrolysis tests comprised 65-98%
      (by weight) of the total HAP emissions quantified in the demonstration-scale
      pouring emission tests. Furthermore, with these two protocols, we appraised the
      relative emission changes that would be associated with (a) replacing
      conventional PUB with collagen-based binder, (b) replacing conventional PUB with
      naphthalene-depleted PUB, and (c) replacing bituminous coal with cellulose for
      making sand molds or cores in the casting process. The relative emission changes
      associated with the use of alternative casting materials exhibited similar trends
      for most of the major HAP species in the demonstration-scale pouring and Curie
      point pyrolysis emission tests. The results indicated that Curie-point pyrolysis
      emission test could be employed as a convenient and cost-effective screening tool
      to identify the major HAP species and to compare the relative HAP emission levels
      for various casting materials.

PMID- 21866939
TI  - Convergent synthesis and discovery of a natural product-inspired paralog
      selective Hsp90 inhibitor.
AB  - A convergent synthesis of benzoquinone ansamycin analogs is described that
      proceeds by a sequence of metallacycle-mediated alkyne-alkyne coupling, followed
      by site- and stereoselective dihydroxylation and global carbamate formation.
      These studies have led to (1) validation of alkyne-alkyne coupling to produce
      geldanamycin analogs that lack the problematic quinone, (2) the discovery that C6
      C7 bis-carbamate functionality is compatible with Hsp90 inhibition, and (3) the
      identification of 1 as a nonquinone geldanamycin-inspired paralog-selective Hsp90
      inhibitor.

PMID- 21866940
TI  - Single-step formation of degradable intracellular biomolecule microreactors.
AB  - Here we present a single-step all-aqueous approach to encapsulate biomolecules
      such as enzymes and proteins into stable microreactors. Key in this method is the
      use of spray-drying of the biomolecules of interest in combination with
      oppositely charged polyelectrolytes and mannitol as the sacrificial template.
      Remarkably, upon spray-drying in the presence of polyelectrolyte, mannitol
      crystallization is suppressed and the obtained amorphous mannitol offers enhanced
      preservation of the biomolecules' activity. Moreover, the use of mannitol allows
      the formation of nanopores within the microparticles upon rehydration of the
      microparticles in aqueous medium and subsequent dissolution of the mannitol. The
      oppositely charged polyelectrolytes provide a polymeric framework which
      stabilizes the microparticles upon rehydration. The versatility of this approach
      is demonstrated using horseradish peroxidase as the model enzyme and ovalbumin as
      the model antigen.

PMID- 21866941
TI  - Synergistic bactericidal activity of Ag-TiO2 nanoparticles in both light and dark
      conditions.
AB  - High-throughput screening was employed to evaluate bactericidal activities of
      hybrid Ag-TiO2 nanoparticles comprising variations in TiO2 crystalline phase, Ag
      content, and synthesis method. Hybrid Ag-TiO2 nanoparticles were prepared by
      either wet-impregnation or UV photo deposition onto both Degussa P25 and DuPont
      R902 TiO2 nanoparticles. The presence of Ag was confirmed by ICP, TEM, and XRD
      analysis. The size of Ag nanoparticles formed on anatase/rutile P25 TiO2
      nanoparticles was smaller than those formed on pure rutile R902. When activated
      by UV light, all hybrid Ag-TiO2 nanoparticles exhibited stronger bactericidal
      activity than UV alone, Ag/UV, or UV/TiO2. For experiments conducted in the dark,
      bactericidal activity of Ag-TiO2 nanoparticles was greater than either bare TiO2
      (inert) or pure Ag nanoparticles, suggesting that the hybrid materials produced a
      synergistic antibacterial effect unrelated to photoactivity. Moreover, less Ag(+)
      dissolved from Ag-TiO2 nanoparticles than from Ag nanoparticles, indicating the
      antibacterial activities of Ag-TiO2 was not only caused by releasing of toxic
      metal ions. It is clear that nanotechnology can produce more effective
      bactericides; however, the challenge remains to identify practical ways to take
      advantage of these exciting new material properties.

PMID- 21866943
TI  - Free energy calculations in electroactive self-assembled monolayers (SAMs):
      impact of the chain length on the redox reaction.
AB  - The free energy approach is used to study the effect of the relative chain length
      of the two constituents of electroactive self-assembled monolayers (SAMs) on
      gold. In this study, the ferrocene groups are exposed to the electrolyte
      solution. This situation is achieved by using shorter diluent alkanethiol chains.
      To this end, the mixed monolayers formed by the self-assembly of 11
      ferrocenylundecanethiol and butanethiol FcC(11)S/C(4)S and of 6
      ferrocenylhexanethiol and butanethiol FcC(6)S/C(4)S onto a gold surface are
      studied. Calculation of enthalpy and entropy differences are also performed using
      molecular simulations. Additionally, the electrochemical signatures of these
      systems are determined to allow a direct comparison with our calculations. The
      thermodynamic properties are discussed in terms of enthalpy and entropy changes.
      Two effects account for the thermodynamic behavior. The first one involves the
      ion pairing between the ferrocenium group and the perchlorate anion. The second
      one concerns the desolvation of the first hydration shell of the anions. Finally,
      this work is also completed with a microscopic description associated with an
      energy characterization of these SAMs as a function of the surface coverage under
      conditions close to experiments.

PMID- 21866942
TI  - A chemical genomic analysis of decoquinate, a Plasmodium falciparum cytochrome b
      inhibitor.
AB  - Decoquinate has single-digit nanomolar activity against in vitro blood stage
      Plasmodium falciparum parasites, the causative agent of human malaria. In vitro
      evolution of decoquinate-resistant parasites and subsequent comparative genomic
      analysis to the drug-sensitive parental strain revealed resistance was conferred
      by two nonsynonymous single nucleotide polymorphisms in the gene encoding
      cytochrome b. The resultant amino acid mutations, A122T and Y126C, reside within
      helix C in the ubiquinol-binding pocket of cytochrome b, an essential subunit of
      the cytochrome bc(1) complex. As with other cytochrome bc(1) inhibitors, such as
      atovaquone, decoquinate has low nanomolar activity against in vitro liver stage
      P. yoelii and provides partial prophylaxis protection when administered to
      infected mice at 50 mg kg(-1). In addition, transgenic parasites expressing yeast
      dihydroorotate dehydrogenase are >200-fold less sensitive to decoquinate, which
      provides additional evidence that this drug inhibits the parasite's mitochondrial
      electron transport chain. Importantly, decoquinate exhibits limited cross
      resistance to a panel of atovaquone-resistant parasites evolved to harbor various
      mutations in cytochrome b. The basis for this difference was revealed by
      molecular docking studies, in which both of these inhibitors were shown to have
      distinctly different modes of binding within the ubiquinol-binding site of
      cytochrome b.

PMID- 21866944
TI  - Oxazolidine synthesis by complementary stereospecific and stereoconvergent
      methods.
AB  - Complementary stereospecific and stereoconvergent reactions for enantioselective
      synthesis of 1,3-oxazolidines are reported. In the presence of a rhodium
      catalyst, reaction of enantioenriched butadiene monoxide with aryl imines is
      stereospecific (99% ee). Alternatively, the reaction of racemic butadiene
      monoxide, in the presence of a chiral palladium or nickel catalyst, provides an
      enantioselective synthesis of 1,3-oxazolidines (up to 94% ee). Synthesis of
      either the cis- or trans-1,3-oxazolidines is also accomplished under catalyst
      control.

PMID- 21866945
TI  - Efficient spectrofluorimetric analysis of single-walled carbon nanotube samples.
AB  - A new method and instrumentation are described for rapid compositional analysis
      of single-walled carbon nanotube (SWCNT) samples. The customized optical system
      uses multiple fixed-wavelength lasers to excite NIR fluorescence from SWCNTs
      individualized in aqueous suspensions. The emission spectra are efficiently
      captured by a NIR spectrometer with InGaAs multichannel detector and then
      analyzed by a computer program that consults a database of SWCNT spectral
      parameters. The identities and relative abundances of semiconducting SWCNTs
      species are quickly deduced and displayed in graphs and tables. Results are found
      to be consistent with those based on manual interpretation of full excitation
      emission scans from a conventional spectrofluorometer. The new instrument also
      measures absorption spectra using a broadband lamp and multichannel
      spectrometers, allowing samples to be automatically characterized by their
      emission efficiencies. The system provides rapid data acquisition and is
      sensitive enough to detect the fluorescence of a few picograms of SWCNTs in ~50
      MUL sample volumes.

PMID- 21866946
TI  - An elegant room temperature procedure for the precise control of composition in
      the Cu-S system.
AB  - A general methodology for the precise control of the final product composition in
      the copper sulfide system has been established for the first time. Cu(2)S,
      prepared by the dissociation of [Cu(tu)(3)]Cl in ethylenediamine, was subjected
      to controlled chemical oxidation by iodine to obtain Cu(2-x) (x = 0.2, 0.25,
      0.88, 1.0) at room temperature. The compositions were characterized by powder X
      ray diffraction, ICP spectroscopy, Raman spectroscopy, and magnetization
      measurements.

PMID- 21866947
TI  - Iron(III)-promoted oxidative coupling of naphthylamines: synthetic and
      mechanistic investigations.
AB  - A facile route to the synthesis of 1,1'-binaphthyl-4,4'-diamines (naphthidines)
      and 1,1'-binaphthyl-2,2'-diamines (BINAMs) was developed by the oxidative
      homocoupling of 1- and 2-naphthylamines, respectively, using FeCl(3) as oxidant
      and K(2)CO(3) as base in 1,2-dichloroethane under ambient conditions. A
      preliminary mechanistic investigation was performed by the ESR spectroscopy and
      intermediate-trapping technique.

PMID- 21866948
TI  - Total synthesis of (+)-lysergic acid.
AB  - A stereocontrolled total synthesis of (+)-lysergic acid (1) is achieved using
      three metal-catalyzed methodologies for the construction of three key rings.
      Highlights of the synthesis include Pd-catalyzed indole synthesis to form the B
      ring, a RCM reaction to form the D ring, and an intramolecular Heck reaction to
      form the C ring.

PMID- 21866949
TI  - Virtual libraries of tetrapyrrole macrocycles. Combinatorics, isomers, product
      distributions, and data mining.
AB  - A software program (PorphyrinViLiGe) has been developed to enumerate the type and
      relative amounts of substituted tetrapyrrole macrocycles in a virtual library
      formed by one of four different classes of reactions. The classes include (1) 4
      fold reaction of n disubstituted heterocycles (e.g., pyrroles or
      diiminoisoindolines) to form beta-substituted porphyrins, beta-substituted
      tetraazaporphyrins, or alpha- or beta-substituted phthalocyanines; (2)
      combination of m aminoketones and n diones to form m * n pyrroles, which upon 4
      fold reaction give beta-substituted porphyrins; (3) derivatization of an 8-point
      tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and
      pyrrole to form meso-substituted porphyrins. The program accommodates variable
      ratios of reactants, reversible or irreversible reaction (reaction classes 1 and
      2), and degenerate modes of formation. Polya's theorem (for enumeration of cyclic
      entities) has also been implemented and provides validation for reaction classes
      3 and 4. The output includes the number and identity of distinct reaction
      accessible substituent combinations, the number and identity of isomers thereof,
      and the theoretical mass spectrum. Provisions for data mining enable assessment
      of the number of products having a chosen pattern of substituents. Examples
      include derivatization of an octa-substituted phthalocyanine with eight reagents
      to afford a library of 2,099,728 members (yet only 6435 distinct substituent
      combinations) and reversible reaction of six distinct disubstituted pyrroles to
      afford 2649 members (yet only 126 distinct substituent combinations). In general,
      libraries of substituted tetrapyrrole macrocycles occupy a synthetically
      accessible region of chemical space that is rich in isomers (>99% or 95% for the
      two examples, respectively).

PMID- 21866950
TI  - Phenolic acids are in vivo atheroprotective compounds appearing in the serum of
      rats after blueberry consumption.
AB  - Blueberries (BB) have recently been shown to have cardioprotective effects and to
      prevent atherosclerosis in rodent models. However, the bioactive compounds in BB
      responsible for these effects have not yet been characterized. Seven phenolic
      acids (7PA) were identified as metabolites in the serum of rats fed diets
      supplemented with 10% freeze-dried BB. In this study, 7PA were evaluated for
      their potential atheroprotective effects in murine macrophage cell line RAW
      264.7. 7PA were found to inhibit LPS-induced mRNA expression and protein levels
      of pro-inflammatory cytokine TNF-alpha and IL-6 by reducing MAPK JNK, p38, and
      Erk1/2 phosphorylation. After treatment with 7PA for 2 weeks, mRNA expression and
      protein levels of scavenger receptor CD36 were decreased (P<0.05), whereas type A
      scavenger receptor (SR-A) remained unchanged. Moreover, foam cell formation
      induced by oxLDL and oxLDL binding to macrophages was also inhibited by 7PA. In
      addition, 7PA increased (P<0.05) expression and protein levels of ATP-binding
      cassette transporter A1 (ABCA1), which facilitates cholesterol efflux and reduces
      cholesterol accumulation in macrophages. In summary, the present study
      demonstrates that certain phenolic acids are potential in vivo atheroprotective
      compounds following BB consumption in the rodent model. Because BB contain many
      phytochemicals, other as yet unidentified bioactive compounds may also be
      important in preventing atherosclerosis in this model and, possibly, in humans.

PMID- 21866952
TI  - Integration of type II nanorod heterostructures into photovoltaics.
AB  - High-quality epitaxial interfaces and delicate control over shape anisotropy make
      nanorod heterostructures (NRHs) with staggered band offsets efficient in
      separating and directing photogenerated carriers. Combined with versatile and
      scalable wet chemical means of synthesis, these salient features of NRHs are
      useful for improving both the performance and the cost-effectiveness of
      photovoltaics (PVs). However, inefficient carrier transport and extraction have
      imposed severe limitations, outweighing the benefits of enhanced charge
      separation. Hence integration of type II NRHs into PVs has thus far been
      unfruitful. Here, we demonstrate PVs that utilize NRHs as an extremely thin
      absorber between electron and hole transporting layers. In the limit approaching
      monolayer thickness, PVs incorporating NRHs have up to three times the short
      circuit current and conversion efficiency over devices made from their single
      component counterparts. Comparisons between linear and curved NRHs are also made,
      revealing the importance of internal geometry and heterointerfacial area for
      enhanced contribution of charge-separated state absorption to photocurrent and in
      contacting charge transport layers.

PMID- 21866951
TI  - Effect of PEGylation on the diffusion and stability of chitosan-DNA polyplexes in
      collagen gels.
AB  - Diffusion through the extracellular matrix (ECM) is a critical step for the
      delivery of nanoparticles and genes. Gene delivery requires a carrier that
      protects the nucleic acid from degradation and facilitates transport. Chitosan is
      a promising carrier. To increase the circulation time, PEGylation of the carrier
      is performed. However, the effect of PEGylation on the transport and stability of
      gene delivery systems in the ECM has only been studied in solutions containing
      ECM components. We used polymerized collagen and collagen-hyaluronic acid (HA)
      gels to study the effects of PEGylation on the diffusion and stability of
      chitosan-DNA polyplexes. We found that PEGylation of the polyplexes was required
      for diffusion to occur, and PEGylation increased the dissociation between DNA and
      chitosan to some extent. The presence of HA had a contradictory role: it
      decreased the penetration depth of PEGylated polyplexes into the gels and
      increased the diffusion of the polyplexes being mixed into the gels.

PMID- 21866953
TI  - Pd-catalytic in situ generation of H2O2 from H2 and O2 produced by water
      electrolysis for the efficient electro-fenton degradation of rhodamine B.
AB  - A novel electro-Fenton process was developed for wastewater treatment using a
      modified divided electrolytic system in which H2O2 was generated in situ from
      electro-generated H2 and O2 in the presence of Pd/C catalyst. Appropriate pH
      conditions were obtained by the excessive H+ produced at the anode. The
      performance of the novel process was assessed by Rhodamine B (RhB) degradation in
      an aqueous solution. Experimental results showed that the accumulation of H2O2
      occurred when the pH decreased and time elapsed. The maximum concentration of
      H2O2 reached 53.1 mg/L within 120 min at pH 2 and a current of 100 mA. Upon the
      formation of the Fenton reagent by the addition of Fe2+, RhB degraded completely
      within 30 min at pH 2 with a pseudo first order rate constant of 0.109 +/- 0.009
      min(-1). An insignificant decline in H2O2 generation and RhB degradation was
      found after six repetitions. RhB degradation was achieved by the chemisorption of
      H2O2 on the Pd/C surface, which subsequently decomposed into *OH upon catalysis
      by Pd0 and Fe2+. The catalytic decomposition of H2O2 to *OH by Fe2+ was more
      powerful than that by Pd0, which was responsible for the high efficiency of this
      novel electro-Fenton process.

PMID- 21866954
TI  - Development of a diphtheria toxin based antiporcine CD3 recombinant immunotoxin.
AB  - Anti-CD3 immunotoxins, which induce profound but transient T-cell depletion in
      vivo by inhibiting eukaryotic protein synthesis in CD3+ cells, are effective
      reagents in large animal models of transplantation tolerance and autoimmune
      disease therapy. A diphtheria toxin based antiporcine CD3 recombinant immunotoxin
      was constructed by fusing the truncated diphtheria toxin DT390 with two identical
      tandem single chain variable fragments (scFv) derived from the antiporcine CD3
      monoclonal antibody 898H2-6-15. The recombinant immunotoxin was expressed in a
      diphtheria-toxin resistant yeast Pichia pastoris strain under the control of the
      alcohol oxidase promoter. The secreted recombinant immunotoxin was purified
      sequentially with hydrophobic interaction chromatography (Butyl 650 M) followed
      by strong anion exchange (Poros 50 HQ). The purified antiporcine CD3 immunotoxin
      was tested in vivo in four animals; peripheral blood CD3+ T-cell numbers were
      reduced by 80% and lymph node T-cells decreased from 74% CD3+ cells pretreatment
      to 24% CD3+ cells remaining in the lymph node following 4 days of immunotoxin
      treatment. No clinical toxicity was observed in any of the experimental swine. We
      anticipate that this conjugate will provide an important tool for in vivo
      depletion of T-cells in swine transplantation models.

PMID- 21866955
TI  - Snooker: a structure-based pharmacophore generation tool applied to class A
      GPCRs.
AB  - G-protein coupled receptors (GPCRs) are important drug targets for various
      diseases and of major interest to pharmaceutical companies. The function of
      individual members of this protein family can be modulated by the binding of
      small molecules at the extracellular side of the structurally conserved
      transmembrane (TM) domain. Here, we present Snooker, a structure-based approach
      to generate pharmacophore hypotheses for compounds binding to this extracellular
      side of the TM domain. Snooker does not require knowledge of ligands, is
      therefore suitable for apo-proteins, and can be applied to all receptors of the
      GPCR protein family. The method comprises the construction of a homology model of
      the TM domains and prioritization of residues on the probability of being ligand
      binding. Subsequently, protein properties are converted to ligand space, and
      pharmacophore features are generated at positions where protein ligand
      interactions are likely. Using this semiautomated knowledge-driven bioinformatics
      approach we have created pharmacophore hypotheses for 15 different GPCRs from
      several different subfamilies. For the beta-2-adrenergic receptor we show that
      ligand poses predicted by Snooker pharmacophore hypotheses reproduce literature
      supported binding modes for ~75% of compounds fulfilling pharmacophore
      constraints. All 15 pharmacophore hypotheses represent interactions with
      essential residues for ligand binding as observed in mutagenesis experiments and
      compound selections based on these hypotheses are shown to be target specific.
      For 8 out of 15 targets enrichment factors above 10-fold are observed in the top
      0.5% ranked compounds in a virtual screen. Additionally, prospectively predicted
      ligand binding poses in the human dopamine D3 receptor based on Snooker
      pharmacophores were ranked among the best models in the community wide GPCR dock
      2010.

PMID- 21866956
TI  - Hierarchically structured one-dimensional TiO2 for protein immobilization, direct
      electrochemistry, and mediator-free glucose sensing.
AB  - A novel one-dimensional hierarchically structured TiO(2) (1DHS TiO(2)) was
      synthesized by a solvothermal method using multiwalled carbon nanotubes (MWCNTs)
      as a template and evaluated for the immobilization of protein and biosensing
      applications. Characterization studies showed that the 1DHS TiO(2) possessed an
      anatase crystalline structure and a large surface area with narrow pore size
      distribution. Fast direct electron transfer was observed for glucose oxidase
      (GOx) immobilized on the 1DHS TiO(2), and excellent electrocatalytic performance
      for glucose detection can be obtained without a mediator. The glucose sensor
      based on the GOx/1DHS TiO(2)-modified electrode had a high sensitivity of 9.90
      MUA mM(-1) cm(-2) and a low detection limit of 1.29 MUM. The fabricated biosensor
      displayed good selectivity and long-term stability, indicating that the novel
      structured TiO(2) is a promising material for the immobilization of biomolecules
      and the fabrication of third-generation biosensors.

PMID- 21866957
TI  - Preferential outward diffusion of Cu during unconventional galvanic replacement
      reactions between HAuCl4 and surface-limited Cu nanocrystals.
AB  - Metal diffusion in nanoscale materials is of great interest, yet the detailed
      kinetic behavior of such diffusion remains elusive. We observe direction
      controlled Cu diffusion during unconventional galvanic replacement reactions
      between surface-limited Cu nanocrystals (NCs) and HAuCl(4). Using presynthesized
      Cu-Cu(1.81)S hetero-oligomer and Cu-Cu(2)S heterodimer NCs as templates and
      reactants, the controlled addition of HAuCl(4) leads to the preferential outward
      diffusion of Cu, visualized by the formation of single-crystalline and straight,
      or polycrystalline and kinked, CuAu nanowires, respectively. The time-dependent
      growth of these nanowires enables determination of nanoscale diffusion
      coefficients of Cu during these processes, for the first time.

PMID- 21866958
TI  - Gyroid nanoporous membranes with tunable permeability.
AB  - Understanding the relevant permeability properties of ultrafiltration membranes
      is facilitated by using materials and procedures that allow a high degree of
      control on morphology and chemical composition. Here we present the first study
      on diffusion permeability through gyroid nanoporous cross-linked 1,2
      polybutadiene (1,2-PB) membranes with uniform pores that, if needed, can be
      rendered hydrophilic. The gyroid porosity has the advantage of isotropic
      percolation with no need for structure prealignment. Closed (skin) or opened
      (nonskin) outer surface can be simply realized by altering the interface energy
      in the process of membrane fabrication. The morphology of the membranes' outer
      surface was investigated by scanning electron microscopy, contact angle, and X
      ray photoelectron spectroscopy. The effective diffusion coefficient of glucose
      decreases from nonskin, to one-sided skin to two-sided skin membranes, much
      faster than expected by a naive resistance-in-series model; the flux through the
      two-sided skin membranes even increases with the membrane thickness. We propose a
      model that captures the physics behind the observed phenomena, as confirmed by
      flow visualization experiments. The chemistry of 1,2-PB nanoporous membranes can
      be controlled, for example, by hydrophilic patterning of the originally
      hydrophobic membranes, which allows for different active porosity toward aqueous
      solutions and, therefore, different permeability. The membrane selectivity is
      evaluated by comparing the effective diffusion coefficients of a series of
      antibiotics, proteins, and other biomolecules; solute permeation is discussed in
      terms of hindered diffusion. The combination of uniform bulk morphology,
      isotropically percolating porosity, controlled surface chemistry, and tunable
      permeability is distinctive for the presented gyroid nanoporous membranes.

PMID- 21866959
TI  - Oligomerization of the serotonin(1A) receptor in live cells: a time-resolved
      fluorescence anisotropy approach.
AB  - The serotonin(1A) receptor is a representative member of the G-protein coupled
      receptor (GPCR) superfamily and serves as an important target in the development
      of therapeutic agents for neuropsychiatric disorders. Oligomerization of GPCRs is
      an important contemporary issue since it is believed to be a crucial determinant
      for cellular signaling. In this work, we monitored the oligomerization status of
      the serotonin(1A) receptor tagged to enhanced yellow fluorescent protein (5
      HT(1A)R-EYFP) in live cells utilizing time-resolved fluorescence anisotropy
      decay. We interpret the unresolved fast component of the observed anisotropy
      decay as fluorescence resonance energy transfer (FRET) between 5-HT(1A)R-EYFP
      molecules (homo-FRET). Homo-FRET enjoys certain advantages over hetero-FRET in
      the analysis of receptor oligomerization. Our results reveal the presence of
      constitutive oligomers of the serotonin(1A) receptor in live cells. We further
      show that the oligomerization status of the receptor is independent of ligand
      stimulation and sphingolipid depletion. Interestingly, acute (but not chronic)
      cholesterol depletion appears to enhance the oligomerization process.
      Importantly, our results are independent of receptor expression level, thereby
      ruling out complications arising due to high expression. These results have
      potential implications in future therapeutic strategies in pathophysiological
      conditions in which serotonin(1A) receptors are implicated.

PMID- 21866961
TI  - Selective water-soluble gelatinase inhibitor prodrugs.
AB  - SB-3CT (1), a selective and potent thiirane-based gelatinase inhibitor, is
      effective in animal models of cancer metastasis and stroke; however, it is
      limited by poor aqueous solubility and extensive metabolism. We addressed these
      issues by blocking the primary site of metabolism and capitalizing on a prodrug
      strategy to achieve >5000-fold increased solubility. The amide prodrugs were
      quantitatively hydrolyzed in human blood to a potent gelatinase inhibitor, ND-322
      (3). The arginyl amide prodrug (ND-478, 5d) was metabolically stable in mouse,
      rat, and human liver microsomes. Both 5d and 3 were nonmutagenic in the Ames II
      mutagenicity assay. The prodrug 5d showed moderate clearance of 0.0582 L/min/kg,
      remained mostly in the extracellular fluid compartment (Vd = 0.0978 L/kg), and
      had a terminal half-life of >4 h. The prodrug 5d had superior pharmacokinetic
      properties than those of 3, making the thiirane class of selective gelatinase
      inhibitors suitable for intravenous administration in the treatment of acute
      gelatinase-dependent diseases.

PMID- 21866960
TI  - Comparative characterization of fungal anthracenone and naphthacenedione
      biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like
      cyclization catalyzed by a dimanganese thioesterase.
AB  - The linear tetracyclic TAN-1612 (1) and BMS-192548 (2) were isolated from
      different filamentous fungal strains and have been examined as potential
      neuropeptide Y and neurokinin-1 receptor antagonists, respectively. Although the
      biosynthesis of fungal aromatic polyketides has attracted much interest in recent
      years, the biosynthetic mechanism for such naphthacenedione-containing products
      has not been established. Using a targeted genome mining approach, we first
      located the ada gene cluster responsible for the biosynthesis of 1 in Aspergillus
      niger ATCC 1015. The connection between 1 and the ada pathway was verified
      through overexpression of the Zn(2)Cys(6)-type pathway-specific transcriptional
      regulator AdaR and subsequent gene expression analysis. The enzymes encoded in
      the ada gene cluster share high sequence similarities to the known apt pathway
      linked to the biosynthesis of anthraquinone asperthecin 3. Subsequent comparative
      investigation of these two highly homologous gene clusters by heterologous
      pathway reconstitution in Saccharomyces cerevisiae revealed a novel alpha
      hydroxylation-dependent Claisen cyclization cascade, which involves a flavin
      dependent monooxygenase that hydroxylates the alpha-carbon of an acyl carrier
      protein-bound polyketide and a bifunctional metallo-beta-lactamase-type
      thioesterase (MbetaL-TE). The bifunctional MbetaL-TE catalyzes the fourth ring
      cyclization to afford the naphthacenedione scaffold upon alpha-hydroxylation,
      whereas it performs hydrolytic release of an anthracenone product in the absence
      of alpha-hydroxylation. Through in vitro biochemical characterizations and metal
      analyses, we verified that the apt MbetaL-TE is a dimanganese enzyme and requires
      both Mn(2+) cations for the observed activities. The MbetaL-TE is the first
      example of a thioesterase in polyketide biosynthesis that catalyzes the Claisen
      like condensation without an alpha/beta hydrolase fold and forms no covalent bond
      with the substrate. These mechanistic features should be general to the
      biosynthesis of tetracyclic naphthacenedione compounds in fungi.

PMID- 21866963
TI  - Chemiluminescence and chemiluminescence resonance energy transfer (CRET) aptamer
      sensors using catalytic hemin/G-quadruplexes.
AB  - The incorporation of hemin into the thrombin/G-quadruplex aptamer assembly or
      into the ATP/G-quadruplex nanostructure yields active DNAzymes that catalyze the
      generation of chemiluminescence. These catalytic processes enable the detection
      of thrombin and ATP with detection limits corresponding to 200 pM and 10 MUM,
      respectively. The conjugation of the antithrombin or anti-ATP aptamers to
      CdSe/ZnS semiconductor quantum dots (QDs) allowed the detection of thrombin or
      ATP through the luminescence of the QDs that is powered by a chemiluminescence
      resonance energy-transfer (CRET) process stimulated by the hemin/G
      quadruplex/thrombin complex or the hemin/G-quadruplex/ATP nanostructure, in the
      presence of luminol/H(2)O(2). The advantages of applying the CRET process for the
      detection of thrombin or ATP, by the resulting hemin/G-quadruplex DNAzyme
      structures, are reflected by low background signals and the possibility to
      develop multiplexed aptasensor assays using different sized QDs.

PMID- 21866962
TI  - Novel peptide-specific quantitative structure-activity relationship (QSAR)
      analysis applied to collagen IV peptides with antiangiogenic activity.
AB  - Angiogenesis is the growth of new blood vessels from existing vasculature.
      Excessive vascularization is associated with a number of diseases including
      cancer. Antiangiogenic therapies have the potential to stunt cancer progression.
      Peptides derived from type IV collagen are potent inhibitors of angiogenesis. We
      wanted to gain a better understanding of collagen IV structure-activity
      relationships using a ligand-based approach. We developed novel peptide-specific
      QSAR models to study the activity of the peptides in endothelial cell
      proliferation, migration, and adhesion inhibition assays. We found that the
      models produced quantitatively accurate predictions of activity and provided
      insight into collagen IV derived peptide structure-activity relationships.

PMID- 21866964
TI  - Novel dimeric cholesteryl derivatives and their smart thixotropic gels.
AB  - Three novel LS(2)-type dimeric-cholesteryl derivatives (1-3), where S is a
      steroidal residue and L stands for a linker connecting the two S residues and
      contains three benzene rings and two amide and two carbamate groups, were
      designed and prepared. The compounds can gel a wide variety of organic solvents
      via three different ways, including mixing at room temperature, a heating-cooling
      cycle, and ultrasound treatment. SEM measurements revealed that the structures
      and the concentrations of the gelators, the nature of the solvent, and the
      preparation method employed have a great effect on the morphologies of the gel
      networks. It was revealed that 1 is a supergelator for DMSO (cgc = 0.04% w/v) and
      that the 1/DMSO gel can be prepared via any of the three methods mentioned above.
      Furthermore, the gel possesses excellent mechanical strength and a very smart
      thixotropic property. FT-IR and temperature- and concentration-dependent (1)H NMR
      spectroscopy studies revealed that hydrogen bonding and pi-pi stacking among the
      molecules of 1 are two important driving forces for the physical gelation of
      DMSO. In addition, XRD analysis confirmed the layered packing structure of 1 in
      its DMSO gel.

PMID- 21866966
TI  - Observation of the urbach tail in the effective density of States in carbon
      nanotubes.
AB  - While a number of studies have reported evidence of localized states in carbon
      nanotube devices, the density distribution of these states has not been reported
      until now. By measuring trap emission current in carbon nanotube field-effect
      transistors, we observe a prominent exponential tail in the density of states
      near the band edge. Since continuous distributions of localized states are
      typically associated with highly disordered systems, this observation was quite
      unexpected in carbon nanotubes, which are nearly ideal crystals. This continuum
      of localized states may explain a variety of phenomena in carbon nanotube
      systems, including the nearly universal lack of n-type conduction in strongly
      gated field-effect transistors. While our focus is on carbon nanotubes, this
      phenomenon may be ubiquitous to low-dimensional semiconductors in nonvacated
      environments.

PMID- 21866965
TI  - Protein glycoengineering enabled by the versatile synthesis of aminooxy glycans
      and the genetically encoded aldehyde tag.
AB  - Homogeneously glycosylated proteins are important targets for fundamental
      research and for biopharmaceutical development. The use of unnatural protein
      glycan linkages bearing structural similarity to their native counterparts can
      accelerate the synthesis of glycoengineered proteins. Here we report an approach
      toward generating homogeneously glycosylated proteins that involves chemical
      attachment of aminooxy glycans to recombinantly produced proteins via oxime
      linkages. We employed the recently introduced aldehyde tag method to obtain a
      recombinant protein with the aldehyde-bearing formylglycine residue at a specific
      site. Complex aminooxy glycans were synthesized using a new route that features N
      pentenoyl hydroxamates as key intermediates that can be readily elaborated
      chemically and enzymatically. We demonstrated the method by constructing site
      specifically glycosylated variants of the human growth hormone.

PMID- 21866967
TI  - Emissive RNA alphabet.
AB  - A fluorescent ribonucleoside alphabet consisting of highly emissive purine
      ((th)A, (th)G) and pyrimidine ((th)U, (th)C) analogues, all derived from
      thieno[3,4-d]pyrimidine as the heterocyclic nucleus, is described. Structural and
      biophysical analyses demonstrated that the emissive analogues are faithful
      isomorphic nucleoside surrogates. Photophysical analysis established that the
      nucleosides offer highly desirable qualities, including visible emission, high
      quantum yield, and responsiveness to environmental perturbations, traits entirely
      lacking in their native counterparts.

PMID- 21866968
TI  - Deposition from dopamine solutions at Ge substrates: an in situ ATR-FTIR study.
AB  - Deposition from dopamine (DA) solutions at germanium (Ge) model substrates was
      monitored under stationary conditions using surface sensitive in situ attenuated
      total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. ATR-FTIR
      spectra of the interfacial organic layer formed upon contact of TRIS buffered
      aqueous DA solutions to a Ge internal reflection element (IRE) showed
      conveniently strong diagnostic IR absorption bands, which were increasing with
      deposition time up to at least 6 h. Comparison of IR spectra of unreacted
      pristine DA, surface reacted, and bulk reacted material confirmed chemical
      reactions of DA to a polymerizate according to the literature. The found IR bands
      could be assigned to aromatic as well as C-O single bond moieties. The kinetic
      courses of the diagnostic band integrals showed an initial increase and
      saturation of the deposition after around 300 min, which could be empirically
      represented by an exponential damping function revealing a rather small kinetic
      constant. Highest deposition levels were found at pH = 8.5 (TRIS buffer or NaOH)
      in contrast to pH = 6.2, where no deposition occurred. Minor deposition was found
      in the presence of salt or at ZnSe instead of Ge due to the absence of reactive
      hydroxyl groups. The concentration dependence of DA deposition showed an initial
      increase and a saturation beginning at around 0.4 mg/mL (0.0022 M), where around
      50 nm thick films featuring granular surface morphologies are formed. The
      adsorbed species are suggested to be smaller bulk reacted DA polymerizate
      particles with reactive end groups. Rinsing the formed films by pure TRIS buffer
      resulted in a time dependent release of deposited organic material by ~23%, which
      could be represented by an exponential decay function. A saturation of the
      release after around 100 min and a larger kinetic constant compared to deposition
      could be determined. The released material is suggested to be larger aggregated
      bulk reacted DA polymerizate particles loosely bound to the surface by weak
      interaction forces.

PMID- 21866969
TI  - Supported molecular iridium catalysts: resolving effects of metal nuclearity and
      supports as ligands.
AB  - The performance of a supported catalyst is influenced by the size and structure
      of the metal species, the ligands bonded to the metal, and the support.
      Resolution of these effects has been lacking because of the lack of
      investigations of catalysts with uniform and systematically varied catalytic
      sites. We now demonstrate that the performance for ethene hydrogenation of
      isostructural iridium species on supports with contrasting properties as ligands
      (electron-donating MgO and electron-withdrawing HY zeolite) can be elucidated on
      the basis of molecular concepts. Spectra of the working catalysts show that the
      catalytic reaction rate is determined by the dissociation of H(2) when the
      iridium, either as mono- or tetra-nuclear species, is supported on MgO and is not
      when the support is the zeolite. The neighboring iridium sites in clusters are
      crucial for activation of both H(2) and C(2)H(4) when the support is MgO but not
      when it is the zeolite, because the electron-withdrawing properties of the
      zeolite support enable even single site-isolated Ir atoms to bond to both
      C(2)H(4) and H(2) and facilitate the catalysis.

PMID- 21866970
TI  - Modulation of physicochemical and conformational properties of kidney bean
      vicilin (phaseolin) by glycation with glucose: implications for structure
      function relationships of legume vicilins.
AB  - The structure-function relationships of plant oligomeric globulins are still not
      fully recognized. The present work investigated the influence of glycation with
      glucose (at 1:50 and 1:100 protein/sugar molar ratios; incubation periods of 2.5,
      5.0, and 10.0 h) on the physicochemical and conformational properties of kidney
      bean vicilin (phaseolin), with the aim of understanding the structure-function
      relationships of legume vicilins. Protein solubility (PS), surface charge
      (isoelectric point) and hydrophobicity (H0), and secondary, tertiary, and/or
      quaternary conformations, as well as the emulsifying activities (emulsifying
      activity and emulsion stability indices, EAI and ESI) were evaluated. The 2.5 h
      incubation period of glycation led to least PS and highest H0, and after that,
      the PS and H0, on the contrary, gradually changed with increasing incubation
      period. The glycation increased the alpha-helix content and highly ordered
      secondary structures (alpha-helix+beta-strand), as evidenced by far-UV circular
      dichroism (CD) spectroscopy. Combined analyses of differential scanning
      calorimetry, intrinsic emission fluorescence, and near-UV CD spectroscopy
      indicated that phaseolin underwent a tertiary conformation unfolding and
      subsequent rearrangement process (to form a new tertiary conformation), whereas
      the quaternary conformational flexibility progressively increased upon increasing
      degree of glycation. The conformation rearrangement was more distinct at the
      1:100 molar ratio than at the 1:50 counterpart. The glycation at 5.0 and 10.0 h
      periods considerably increased the EAI, but only at the 1:50 molar ratio was the
      ESI progressively increased with the incubation period. These results confirmed
      that besides surface properties (e.g., PS and H0), the flexibility in tertiary
      and/or quaternary conformations played a major role in the emulsifying properties
      of glycated vicilins. The findings would have important implications for
      understanding the structure-function relationships of legume oligomeric
      globulins, thus providing a direction to further improve the surface-related
      functional properties of these proteins.

PMID- 21866971
TI  - Mechanistic toxicity evaluation of uncoated and PEGylated single-walled carbon
      nanotubes in neuronal PC12 cells.
AB  - We investigated and compared the concentration-dependent cytotoxicity of single
      walled carbon nanotubes (SWCNTs) and SWCNTs functionalized with polyethylene
      glycol (SWCNT-PEGs) in neuronal PC12 cells at the biochemical, cellular, and gene
      expressional levels. SWCNTs elicited cytotoxicity in a concentration-dependent
      manner, and SWCNT-PEGs exhibited less cytotoxic potency than uncoated SWCNTs.
      Reactive oxygen species (ROS) were generated in both a concentration- and surface
      coating-dependent manner after exposure to these nanomaterials, indicating
      different oxidative stress mechanisms. More specifically, gene expression
      analysis showed that the genes involved in oxidoreductases and antioxidant
      activity, nucleic acid or lipid metabolism, and mitochondria dysfunction were
      highly represented. Interestingly, alteration of the genes is also surface
      coating-dependent with a good correlation with the biochemical data. These
      findings suggest that surface functionalization of SWCNTs decreases ROS-mediated
      toxicological response in vitro.

PMID- 21866972
TI  - Direct DNA conjugation to star polymers for controlled reversible assemblies.
AB  - Polymer biomolecule hybrids represent a powerful class of highly customizable
      nanomaterials. Here, we report star-polymer conjugates with DNA using a
      "ligandless" Cu(I) promoted azide-alkyne cycloaddition click reaction. The
      multivalency of the star-polymer architecture allows for the concomitant
      conjugation of other molecules along with the DNA, and the conjugation method
      provides control over the DNA orientation. The star-polymer DNA nanoparticles are
      shown to assemble into higher-order nanoassemblies through hybridization.
      Further, we show that the DNA strands can be utilized in controlled disassembly
      of the nanostructures.

PMID- 21866973
TI  - Energy landscape and global optimization for a frustrated model protein.
AB  - The three-color (BLN) 69-residue model protein was designed to exhibit frustrated
      folding. We investigate the energy landscape of this protein using
      disconnectivity graphs and compare it to a Go model, which is designed to reduce
      the frustration by removing all non-native attractive interactions. Finding the
      global minimum on a frustrated energy landscape is a good test of global
      optimization techniques, and we present calculations evaluating the performance
      of basin-hopping and genetic algorithms for this system. Comparisons are made
      with the widely studied 46-residue BLN protein. We show that the energy landscape
      of the 69-residue BLN protein contains several deep funnels, each of which
      corresponds to a different beta-barrel structure.

PMID- 21866974
TI  - Kinetics of ligand binding to membrane receptors from equilibrium fluctuation
      analysis of single binding events.
AB  - Equilibrium fluctuation analysis of single binding events has been used to
      extract binding kinetics of ligand interactions with cell-membrane bound
      receptors. Time-dependent total internal reflection fluorescence (TIRF) imaging
      was used to extract residence-time statistics of fluorescently stained liposomes
      derived directly from cell membranes upon their binding to surface-immobilized
      antibody fragments. The dissociation rate constants for two pharmaceutical
      relevant antibodies directed against different B-cell expressed membrane proteins
      was clearly discriminated, and the affinity of the interaction could be
      determined by inhibiting the interaction with increasing concentrations of
      soluble antibodies. The single-molecule sensitivity made the analysis possible
      without overexpressed membrane proteins, which makes the assay attractive in
      early drug-screening applications.

PMID- 21866975
TI  - X-ray fluorescence analysis of hexavalent chromium using Kbeta satellite peak
      observed as counterpart of X-ray absorption near-edge structure pre-edge peak.
AB  - A Kbeta satellite peak in X-ray fluorescence (XRF) spectra is observed as a
      counterpart of the pre-edge peak of the X-ray absorption near edge structure
      (XANES). In Kbeta emission of chromium, a small satellite peak is observed at
      5.983-5.988 keV only for hexavalent chromium compounds such as CrO(3),
      Na(2)CrO(7).2H(2)O, Na(2)CrO(4).4H(2)O, K(2)Cr(2)O(7), K(2)CrO(4),
      Zn(2)CrO(4)(OH)(2).2H(2)O, PbCrO(4), and BaCrO(4), together with the main peak at
      5.947 keV, while trivalent chromium compounds such as Cr(2)O(3) and
      Cr(OH)(3).nH(2)O show only the main peak at 5.947 keV. This corresponds to the
      fact that the K pre-edge peak in XANES is observed only for the hexavalent
      chromium compounds. The electronic level causing the satellite peak is almost at
      the same energy level as that causing the pre-edge peak. Our finding not only
      affects the interpretation of the origin of the pre-edge peaks but also leads to
      the simple speciation method of chromium compounds using XRF.

PMID- 21866976
TI  - Substituent effects on the reversibility of furan-maleimide cycloadditions.
AB  - The effects of furan and maleimide substitution on the dynamic reversibility of
      their Diels-Alder reactivity have been investigated computationally and by (1)H
      NMR spectroscopy. Furan and furan derivatives bearing methoxy, methyl, or formyl
      groups at their 2- or 3-positions were investigated with maleimide and maleimide
      derivatives bearing N-methyl, N-allyl, and N-phenyl substituents. Computational
      predictions indicate that electronic and regiochemical effects of furan
      substitution significantly influence their Diels-Alder reactivity with maleimide,
      with reaction free energies of exo adduct formation ranging from DeltaG = -9.4 to
      0.9 kcal/mol and transition state barriers to exo adduct formation ranging from
      DeltaG(?) = 18.9 to 25.6 kcal/mol. Much less variation was observed for the
      reactivity of N-substituted maleimide derivatives and furan, with reaction and
      transition state free energies each falling within a range of 1.1 kcal/mol.
      Dynamic exchange experiments monitored by (1)H NMR spectroscopy support
      computational predictions. The results indicate the reactivity and reversibility
      of furan-maleimide cycloadditions can be tuned significantly through the addition
      of appropriate substituents and have implications in the use of furan and
      maleimide derivatives in the construction of thermally responsive organic
      materials.

PMID- 21866977
TI  - Effect of ligand substitution on the interaction between anisotropic Dy(III) ions
      and 57Fe nuclei in Fe2Dy2 coordination clusters.
AB  - A series of [Fe(2)Dy(2)(OH)(2)(teaH)(2)(RC(6)H(4)COO)(6)] compounds has been
      synthesized and studied using Mossbauer spectroscopy. It is suggested that the
      local crystal field of the Dy(III) centers and the external magnetic field can
      control their shape anisotropy and thus the interactions between the dysprosium
      and iron centers.

PMID- 21866978
TI  - Voltammetric behavior of gold nanotrench electrodes.
AB  - We report the fabrication and electrochemical response of a gold nanoband
      electrode located at the bottom of a glass/epoxy nanotrench, hereafter referred
      to as a gold nanotrench electrode. Gold nanotrench electrodes of 12.5 and 40 nm
      in width with various depths from a few tens of nanometers to approximately 4 MUm
      are fabricated and further characterized by cyclic voltammetry. The fabrication
      of a Au nanotrench electrode follows a simple electrochemical etching process in
      which a small AC signal is applied to an inlaid Au nanoband electrode submersed
      in a NaCl solution. The voltammetric behavior of a Au nanotrench electrode is
      characterized by a quasi-steady-state response at lower scan rates (e.g., <1 V/s
      for a 12.5-nm-wide electrode). We present an analytical expression for the quasi
      steady-state diffusion-limited current of the nanotrench electrode based upon the
      analysis of the mass-transport resistance. Finite-element simulation of steady
      state and transient voltammetric responses of the nanotrench electrodes provides
      additional insights for the analytical model. Peak-shaped transient voltammetric
      responses were observed at scan rates as low as 5 V/s for both inlaid and
      nanotrench electrodes. This result may suggest that the exposed area of the
      nanoband electrode is much greater than that expected from the fabrication of the
      inlaid bands. However, the extent to which this is seen is greatly decreased in
      the nanotrench electrode by a smoothing effect during etching. Our results
      confirm previous reports of excess overhanging metal and delamination crack
      contributing significantly to the shape and magnitude of the voltammetric
      response.

PMID- 21866979
TI  - Luminescent lanthanide-functionalized gold nanoparticles: exploiting the
      interaction with bovine serum albumin for potential sensing applications.
AB  - As luminescent surface-functionalized gold nanoparticles emerged as potential
      powerful analytical tools in the biomedical fields, understanding the interaction
      of such systems with proteins has become crucial. In the present study, the
      interaction of luminescent water-soluble gold nanoparticles (AuNP-1.Eu-nta),
      obtained through the self-assembly of a naphthalene beta-diketone antenna with a
      Eu(III) cyclen complex tethered to the gold surface via a C(12) alkyl thiol
      spacer, with bovine serum albumin (BSA) was investigated. The changes in the UV
      visible absorption and fluorescence spectra of both the antenna and protein, as
      well as in the time-resolved Eu(III)-centered emission, of the resulting self
      assembly were monitored, at physiological pH, as a function of the BSA
      concentration. We demonstrate that the Eu(III) emission arising from the self
      assembly on the AuNP surface is almost completely quenched upon addition of BSA.
      Binding constant determination clearly showed that the sensitizing antenna was
      not displaced and that the quenching was the result of the interaction between
      the antenna and BSA. Detailed spectroscopic studies performed on the nta-BSA
      system brought a better insight in the strength of such interaction as well as
      its effect on the protein secondary structure. Finally, the information gathered
      on each system resulted in applying AuNP-1.Eu-nta-BSA for the luminescent
      detection of drugs via the perturbation of the nta-BSA interaction. Competitive
      titrations using ibuprofen and warfarin showed that nta was located in the
      binding site II of BSA and that the presence of warfarin, a site I drug, did not
      interfere with the detection of site II ibuprofen.

PMID- 21866980
TI  - The "anthracene problem": closed-form conjugated-circuit models of ring currents
      in linear polyacenes.
AB  - Conjugated-circuit models for induced pi ring currents differ in the types of
      circuit that they include and the weights attached to them. Choice of circuits
      for general pi systems can be expressed compactly in terms of matchings of the
      circuit-deleted molecular graph. Variants of the conjugated-circuit model for
      induced pi currents are shown to have simple closed-form solutions for linear
      polyacenes. Despite differing assumptions about the effect of cycle area, all the
      models predict the most intense perimeter current in the central rings, in
      general agreement with ab initio current-density maps. All tend to overestimate
      the rate of increase with N of the central ring current for the [N]polyacene, in
      comparison with molecular-orbital treatments using ipsocentric ab initio, pseudo
      pi, and Huckel-London approaches.

PMID- 21866981
TI  - Dynamical behavior near a liquid-liquid phase transition in simulations of
      supercooled water.
AB  - We examine the behavior of the diffusion coefficient of the ST2 model of water
      over a broad region of the phase diagram via molecular dynamics simulations. The
      ST2 model has an accessible liquid-liquid transition between low-density and high
      density phases, making the model an ideal candidate to explore the impacts of the
      liquid-liquid transition on dynamics. We locate characteristic dynamical loci in
      the phase diagram and compare them with the previously investigated thermodynamic
      loci. The low-density liquid phase shows a crossover from non-Arrhenius to
      Arrhenius behavior, signaling the onset of a crossover from fragile-to-strong
      behavior. We explain this crossover in terms of the asymptotic approach of the
      low-density liquid to a random tetrahedral network and show that the temperature
      dependence of the diffusion coefficient over a wide temperature range can be
      simply related to the concentration of defects in the network. Our findings thus
      confirm that the low-density phase of ST2 water is a well-defined metastable
      liquid.

PMID- 21866982
TI  - Occurrence, sensory impact, formation, and fate of damascenone in grapes, wines,
      and other foods and beverages.
AB  - Among plant-derived odorants, damascenone is one of the most ubiquitous,
      sometimes occurring as an apparent natural product but more commonly occurring in
      processed foodstuffs and beverages. It has been widely reported as a component of
      alcoholic beverages, particularly of wines made from the grape Vitis vinifera .
      Although damascenone has one of the lowest ortho- and retronasal detection
      thresholds of any odorant, its contribution to the sensory properties of most
      products remains poorly understood. Damascenone can be formed by acid-catalyzed
      hydrolyses of plant-derived apocarotenoids, in both aglycon and glycoconjugated
      forms. These reactions can account for the formation of damascenone in some, but
      not all, products. In wine, damascenone can also be subject to degradation
      processes, particularly by reaction with sulfur dioxide.

PMID- 21866983
TI  - Fragmentation methods: a route to accurate calculations on large systems.

PMID- 21866984
TI  - Peptide coupling reagents, more than a letter soup.

PMID- 21866986
TI  - Amplitude-mode dynamics of polariton condensates.
AB  - We study the stability of collective amplitude excitations in nonequilibrium
      polariton condensates. These excitations correspond to renormalized upper
      polaritons and to the collective amplitude modes of atomic gases and
      superconductors. They would be present following a quantum quench or could be
      created directly by resonant excitation. We show that uniform amplitude
      excitations are unstable to the production of excitations at finite wave vectors,
      leading to the formation of density-modulated phases. The physical processes
      causing the instabilities can be understood by analogy to optical parametric
      oscillators and the atomic Bose supernova.

PMID- 21866985
TI  - Psychosocial costs of racism to Whites: Understanding patterns among university
      students.
AB  - This investigation adds to the growing body of scholarship on the psychosocial
      costs of racism to Whites (PCRW), which refer to consequences of being in the
      dominant position in an unjust, hierarchical system of societal racism. Extending
      research that identified 5 distinct constellations of costs of racism (L. B.
      Spanierman, V. P. Poteat, A. M. Beer, & P. I. Armstrong, 2006), the authors used
      multinomial logistic regression in the current study to examine what factors
      related to membership in 1 of the 5 PCRW types during the course of an academic
      year. Among a sample of White university freshmen (n = 287), the authors found
      that (a) diversity attitudes (i.e., universal diverse orientation and unawareness
      of privilege) explained PCRW type at entrance, (b) PCRW type at entrance
      explained participation in interracial friendships at the end of the year, (c)
      45% of participants changed PCRW type during the course of the year, and (d)
      among those who changed type, particular PCRW types at entrance resulted in
      greater likelihood of membership in particular PCRW types at the end of the year.
      (PsycINFO Database Record (c) 2010 APA, all rights reserved).

PMID- 21866987
TI  - Computational difficulty of computing the density of states.
AB  - We study the computational difficulty of computing the ground state degeneracy
      and the density of states for local Hamiltonians. We show that the difficulty of
      both problems is exactly captured by a class which we call #BQP, which is the
      counting version of the quantum complexity class quantum Merlin Arthur. We show
      that #BQP is not harder than its classical counting counterpart #P, which in turn
      implies that computing the ground state degeneracy or the density of states for
      classical Hamiltonians is just as hard as it is for quantum Hamiltonians.

PMID- 21866988
TI  - Entropy of isolated quantum systems after a quench.
AB  - A diagonal entropy, which depends only on the diagonal elements of the system's
      density matrix in the energy representation, has been recently introduced as the
      proper definition of thermodynamic entropy in out-of-equilibrium quantum systems.
      We study this quantity after an interaction quench in lattice hard-core bosons
      and spinless fermions, and after a local chemical potential quench in a system of
      hard-core bosons in a superlattice potential. The former systems have a chaotic
      regime, where the diagonal entropy becomes equivalent to the equilibrium
      microcanonical entropy, coinciding with the onset of thermalization. The latter
      system is integrable. We show that its diagonal entropy is additive and different
      from the entropy of a generalized Gibbs ensemble, which has been introduced to
      account for the effects of conserved quantities at integrability.

PMID- 21866989
TI  - Confirmation of the Copernican principle at Gpc radial scale and above from the
      kinetic Sunyaev-Zel'dovich effect power spectrum.
AB  - The Copernican principle, a cornerstone of modern cosmology, remains largely
      unproven at the Gpc radial scale and above. Here will show that violations of
      this type will inevitably cause a first order anisotropic kinetic Sunyaev
      Zel'dovich effect. If large scale radial inhomogeneities have an amplitude large
      enough to explain the "dark energy" phenomena, the induced kinetic Sunyaev
      Zel'dovich power spectrum will be much larger than the Atacama Cosmology
      Telescope and/or South Pole Telescope upper limit. This single test confirms the
      Copernican principle and rules out the adiabatic void model as a viable
      alternative to dark energy.

PMID- 21866990
TI  - Supersymmetry and its spontaneous breaking in the random field Ising model.
AB  - We provide a resolution of one of the long-standing puzzles in the theory of
      disordered systems. By reformulating the functional renormalization group for the
      critical behavior of the random field Ising model in a superfield formalism, we
      are able to follow the associated supersymmetry and its spontaneous breaking
      along the functional renormalization group flow. Breaking is shown to occur below
      a critical dimension d(DR) ? 5.1 and leads to a breakdown of the "dimensional
      reduction" property. We compute the critical exponents as a function of dimension
      and give evidence that scaling is described by three independent exponents.

PMID- 21866991
TI  - Paraelectricity in magnetized massless QED.
AB  - We show that the chiral-symmetry-broken phase of massless QED in the presence of
      a magnetic field exhibits strong paraelectricity. A large anisotropic electric
      susceptibility develops in the infrared region, where most of the fermions are
      confined to their lowest Landau level, and dynamical mass and anomalous magnetic
      moment are generated via the magnetic catalysis mechanism. The nonperturbative
      nature of this effect is reflected in the dependence of the electric
      susceptibility on the fine-structure constant. The strong paraelectricity is
      linked to the electric dipole moments of the particle-antiparticle pairs that
      form the chiral condensate. The significant electric susceptibility can be used
      as a probe to detect the realization of the magnetic catalysis of chiral symmetry
      breaking in physical systems.

PMID- 21866992
TI  - Indication of electron neutrino appearance from an accelerator-produced off-axis
      muon neutrino beam.
AB  - The T2K experiment observes indications of nu(MU) -> nu(e) appearance in data
      accumulated with 1.43*10(20) protons on target. Six events pass all selection
      criteria at the far detector. In a three-flavor neutrino oscillation scenario
      with |Deltam(23)(2)| = 2.4*10(-3)  eV(2), sin(2)2theta(23) = 1 and
      sin(2)2theta(13) = 0, the expected number of such events is 1.5+/-0.3(syst).
      Under this hypothesis, the probability to observe six or more candidate events is
      7*10(-3), equivalent to 2.5sigma significance. At 90% C.L., the data are
      consistent with 0.03(0.04) < sin(2)2theta(13) < 0.28(0.34) for delta(CP) = 0 and
      a normal (inverted) hierarchy.

PMID- 21866998
TI  - Attosecond control in photoionization of hydrogen molecules.
AB  - We report experiments where hydrogen molecules were dissociatively ionized by an
      attosecond pulse train in the presence of a near-infrared field. Fragment ion
      yields from distinguishable ionization channels oscillate with a period that is
      half the optical cycle of the IR field. For molecules aligned parallel to the
      laser polarization axis, the oscillations are reproduced in two-electron quantum
      simulations, and can be explained in terms of an interference between ionization
      pathways that involve different harmonic orders and a laser-induced coupling
      between the 1ssigma(g) and 2psigma(u) states of the molecular ion. This leads to
      a situation where the ionization probability is sensitive to the instantaneous
      polarization of the molecule by the IR electric field and demonstrates that we
      have probed the IR-induced electron dynamics with attosecond pulses.

PMID- 21866999
TI  - Multiple recapture of electrons in multiple ionization of the argon dimer by a
      strong laser field.
AB  - We observe multiply frustrated tunneling ionization-induced dissociation of the
      argon dimers by intense linearly polarized ultrashort laser pulses. By measuring
      the kinetic energy release and angular distribution of the Coulomb explosion of
      up to eightfold ionized argon dimers, we can trace the recapture of up to two
      electrons to Rydberg states of the highly charged compound at the end of the
      laser pulse. Upon dissociation of the dimer, the Rydberg electron prefers to
      localize at the atomic ion with the higher charge state. We probe the electron
      recapture dynamics by a time-delayed weak pulse.

PMID- 21866997
TI  - Femtosecond stimulated Raman scattering picosecond molecular thermometry in
      condensed phases.
AB  - We demonstrate the capability of femtosecond stimulated Raman scattering (FSRS)
      data to measure the temperature of condensed matter at the molecular vibrational
      level. We report the temperature dependence of Raman loss to Raman gain ratios
      for low frequency modes (<300  cm(-1)) in a CaCO3 single crystal from cryogenic
      to room temperature, which is shown to be in agreement with theoretical
      predictions. We also report the measurements of nonequilibrium time evolution of
      mode specific vibrational temperatures in the CaCO3 single crystal to demonstrate
      that FSRS can measure temperature on picosecond time scales. Finally, we point
      out the unique origin of this temperature dependent anti-Stokes to Stokes ratio
      in stimulated Raman, which is not present in other coherent Raman spectroscopies.
      These measurements require no material dependent parameters or prior calibration.

PMID- 21866994
TI  - Observation of the h(c)(1P) Using e+ e- collisions above the DD threshold.
AB  - Using 586  pb(-1) of e+ e- collision data at E(c.m.) = 4170  MeV, produced at the
      Cornell Electron Storage Ring collider and collected with the CLEO-c detector, we
      observe the process e+ e- -> pi+ pi- h(c)(1P). We measure its cross section to be
      15.6+/-2.3+/-1.9+/-3.0  pb, where the third error is due to the external
      uncertainty on the branching fraction of psi(2S) -> pi0 h(c)(1P), which we use
      for normalization. We also find evidence for e+ e- -> etah(c)(1P) at 4170 MeV at
      the 3sigma level and see hints of a rise in the e+ e- -> pi+ pi- h(c)(1P) cross
      section at 4260 MeV.

PMID- 21867000
TI  - QED theory of the nuclear magnetic shielding in hydrogenlike ions.
AB  - The shielding of the nuclear magnetic moment by the bound electron in
      hydrogenlike ions is calculated ab initio with inclusion of relativistic,
      nuclear, and quantum electrodynamics (QED) effects. The QED correction is
      evaluated to all orders in the nuclear binding strength parameter and,
      independently, to the first order in the expansion in this parameter. The results
      obtained lay the basis for the high-precision determination of nuclear magnetic
      dipole moments from measurements of the g factor of hydrogenlike ions.

PMID- 21867001
TI  - QED effects in molecules: test on rotational quantum states of H2.
AB  - Quantum electrodynamic effects have been systematically tested in the progression
      of rotational quantum states in the X 1Sigma(g)(+), v=0 vibronic ground state of
      molecular hydrogen. High-precision Doppler-free spectroscopy of the EF
      1Sigma(g)(+)-X 1Sigma(g)(+) (0,0) band was performed with 0.005  cm(-1) accuracy
      on rotationally hot H2 (with rotational quantum states J up to 16). QED and
      relativistic contributions to rotational level energies as high as 0.13  cm(-1)
      are extracted, and are in perfect agreement with recent calculations of QED and
      high-order relativistic effects for the H2 ground state.

PMID- 21867002
TI  - Photon-photon gates in Bose-Einstein condensates.
AB  - It has recently been shown that light can be stored in Bose-Einstein condensates
      for over a second. Here we propose a method for realizing a controlled phase gate
      between two stored photons. The photons are both stored in the ground state of
      the effective trapping potential inside the condensate. The collision-induced
      interaction is enhanced by adiabatically increasing the trapping frequency and by
      using a Feshbach resonance. A controlled phase shift of pi can be achieved in 1 s
      or less.

PMID- 21867003
TI  - Radiation damping in atomic photonic crystals.
AB  - The force exerted on a material by an incident beam of light is dependent upon
      the material's velocity in the laboratory frame of reference. This velocity
      dependence is known to be difficult to measure, as it is proportional to the
      incident optical power multiplied by the ratio of the material velocity to the
      speed of light. Here we show that this typically tiny effect is greatly amplified
      in multilayer systems composed of resonantly absorbing atoms exhibiting
      ultranarrow photonic band gaps. The amplification effect for optically trapped
      87Rb is shown to be as much as 3 orders of magnitude greater than for
      conventional photonic-band-gap materials. For a specific pulsed regime, damping
      remains observable without destroying the system and significant for material
      velocities of a few ms(-1).

PMID- 21867004
TI  - Collective dynamics in optomechanical arrays.
AB  - Optomechanical systems couple light stored inside an optical cavity to the motion
      of a mechanical mode. Recent experiments have demonstrated setups, such as
      photonic crystal structures, that in principle allow one to confine several
      optical and vibrational modes on a single chip. Here we start to investigate the
      collective nonlinear dynamics in arrays of coupled optomechanical cells. We show
      that such "optomechanical arrays" can display synchronization, and that they can
      be described by an effective Kuramoto-type model.

PMID- 21867005
TI  - Dynamics of coherent and incoherent emission from an artificial atom in a 1D
      space.
AB  - We study dynamics of a two-level superconducting quantum system, analogous to a
      natural atom in an open space, by measuring the evolution of its coherent and
      incoherent emission. The emitted waves containing full information about the
      states of the artificial atom are efficiently collected due to strong atom
      transmission-line coupling. This allows us to do simultaneous measurements of all
      the quantum state projections and perform a full characterization of the system.
      We derive coherence times and extract the two-time correlation function from the
      dynamics of the coherent emission.

PMID- 21867006
TI  - Classical analogue of electromagnetically induced transparency with a metal
      superconductor hybrid metamaterial.
AB  - Metamaterials are engineered materials composed of small electrical circuits
      producing novel interactions with electromagnetic waves. Recently, a new class of
      metamaterials has been created to mimic the behavior of media displaying
      electromagnetically induced transparency (EIT). Here we introduce a planar EIT
      metamaterial that creates a very large loss contrast between the dark and
      radiative resonators by employing a superconducting Nb film in the dark element
      and a normal-metal Au film in the radiative element. Below the critical
      temperature of Nb, the resistance contrast opens up a transparency window along
      with a large enhancement in group delay, enabling a significant slowdown of
      waves. We further demonstrate precise control of the EIT response through changes
      in the superfluid density. Such tunable metamaterials may be useful for
      telecommunication because of their large delay-bandwidth products.

PMID- 21867007
TI  - Origin for ellipticity of high-order harmonics generated in atomic gases and the
      sublaser-cycle evolution of harmonic polarization.
AB  - We investigate numerically and analytically the polarization properties of high
      order harmonics generated by an atom in intense elliptically polarized laser
      field. The offset angle of the harmonic polarization ellipse can be well
      described with the semiclassic "simple-man" high-harmonic generation model. The
      harmonic ellipticity itself, however, can be hardly understood within this model.
      We show that this ellipticity originates from quantum-mechanical uncertainty of
      the electron motion. We develop a theoretical approach describing this
      ellipticity and, more generally, the time evolution of the high-harmonic
      polarization state within the laser cycle. The analytical results are verified
      with the exact numerical solution; to make the comparison accurately, we develop
      a specific technique for separating the contributions of quantum paths in the
      numerical calculation.

PMID- 21867008
TI  - Theory of fishnet negative-index optical metamaterials.
AB  - We theoretically study fishnet metamaterials at optical frequencies. In contrast
      with earlier works, we provide a microscopic description by tracking the
      transversal and longitudinal flows of energy through the fishnet mesh composed of
      intersecting subwavelength plasmonic waveguides. The analysis is supported by a
      semianalytical model based on surface-plasmon coupled-mode equations, which
      provides accurate formulas for the fishnet refractive index, including the real
      negative and imaginary parts. The model simply explains how the surface plasmons
      couple at the waveguide intersections, and it shines new light on the fishnet
      negative-index paradigm at optical frequencies. Extension of the theory for loss
      compensated metamaterials with gain media is also presented.

PMID- 21866995
TI  - Observation of the decay B- -> D(s)((*)+) K- l- nu(l).
AB  - We report the observation of the decay B- -> D(s)((*)+) K- l- nu(l) based on 342 
      fb(-1) of data collected at the Upsilon(4S) resonance with the BABAR detector at
      the PEP-II e+ e- storage rings at SLAC. A simultaneous fit to three D(s)(+) decay
      chains is performed to extract the signal yield from measurements of the squared
      missing mass in the B meson decay. We observe the decay B- -> D(s)((*)+) K- l-
      nu(l) with a significance greater than 5 standard deviations (including
      systematic uncertainties) and measure its branching fraction to be B(B- ->
      D(s)((*)+) K- l- nu(l)) = [6.13(-1.03)(+1.04)(stat)+/-0.43(syst)+/
      0.51(B(D(s)))]*10(-4), where the last error reflects the limited knowledge of the
      D(s) branching fractions.

PMID- 21867009
TI  - Floating carpets and the delamination of elastic sheets.
AB  - We investigate the deformation of a thin elastic sheet floating on a liquid
      surface and subject to a uniaxial compression. We show that at a critical
      compression the sheet delaminates from the liquid over a finite region forming a
      delamination "blister." This blistering regime adds to the wrinkling and
      localized folding regimes that have been studied previously. The transition from
      wrinkled to blistered states occurs when delamination becomes energetically
      favorable compared with wrinkling. We determine the initial blister size and the
      evolution of blister size with continuing compression before verifying our
      theoretical results with experiments at a macroscopic scale.

PMID- 21867011
TI  - Rare fluctuations and large-scale circulation cessations in turbulent convection.
AB  - In turbulent Rayleigh-Benard convection, a large-scale circulation (LSC) develops
      in a nearly vertical plane and is maintained by rising and falling plumes
      detaching from the unstable thermal boundary layers. Rare but large fluctuations
      in the LSC amplitude can lead to extinction of the LSC (a cessation event),
      followed by the reemergence of another LSC with a different (random) azimuthal
      orientation. We extend previous models of the LSC dynamics to include momentum
      and thermal diffusion in the azimuthal plane and calculate the tails of the
      probability distributions of both the amplitude and azimuthal angle. Our
      analytical results are in very good agreement with the experimental data.

PMID- 21867012
TI  - Lagrangian formulation of turbulent premixed combustion.
AB  - The lagrangian point of view is adopted to study turbulent premixed combustion.
      The evolution of the volume fraction of combustion products is established by the
      Reynolds transport theorem. It emerges that the burned-mass fraction is led by
      the turbulent particle motion, by the flame front velocity, and by the mean
      curvature of the flame front. A physical requirement connecting particle
      turbulent dispersion and flame front velocity is obtained from equating the
      expansion rates of the flame front progression and of the unburned particles
      spread. The resulting description compares favorably with experimental data. In
      the case of a zero-curvature flame, with a non-markovian parabolic model for
      turbulent dispersion, the formulation yields the Zimont equation extended to all
      elapsed times and fully determined by turbulence characteristics. The exact
      solution of the extended Zimont equation is calculated and analyzed to bring out
      different regimes.

PMID- 21867010
TI  - Three-dimensional to two-dimensional crossover in the hydrodynamic interactions
      between micron-scale rods.
AB  - Moving micron-scale objects are strongly coupled to each other by hydrodynamic
      interactions. The strength of this coupling decays with the inverse particle
      separation when the two objects are sufficiently far apart. It has been recently
      demonstrated that the reduced dimensionality of a thin fluid layer gives rise to
      longer-ranged, logarithmic coupling. Using holographic tweezers we show that
      microrods display both behaviors interacting like point particles in three
      dimensions at large distances and like point particles in two dimensions for
      distances shorter then their length. We derive a simple analytical expression
      that fits our data remarkably well and further validate it with finite element
      analysis.

PMID- 21867013
TI  - Demonstration of a narrow energy spread, ~0.5  GeV electron beam from a two-stage
      laser wakefield accelerator.
AB  - Laser wakefield acceleration of electrons holds great promise for producing
      ultracompact stages of GeV scale, high-quality electron beams for applications
      such as x-ray free electron lasers and high-energy colliders. Ultrahigh intensity
      laser pulses can be self-guided by relativistic plasma waves (the wake) over tens
      of vacuum diffraction lengths, to give >1  GeV energy in centimeter-scale low
      density plasmas using ionization-induced injection to inject charge into the wake
      even at low densities. By restricting electron injection to a distinct short
      region, the injector stage, energetic electron beams (of the order of 100 MeV)
      with a relatively large energy spread are generated. Some of these electrons are
      then further accelerated by a second, longer accelerator stage, which increases
      their energy to ~0.5  GeV while reducing the relative energy spread to <5% FWHM.

PMID- 21867014
TI  - Ar+ and Xe+ velocities near the presheath-sheath boundary in an Ar/Xe discharge.
AB  - The velocities of Ar+ and Xe+ ions near the presheath-sheath boundary in an Ar/Xe
      discharge are studied by particle-in-cell Monte Carlo simulation. For a pure
      argon discharge the argon ion has almost the same velocity profile as it does in
      the mixture of argon and xenon. Similarly, for a xenon discharge the xenon ion
      has almost the same velocity profile as it does in the mixture of argon and
      xenon. The ion speed at the sheath-presheath boundary is the same for an ion in a
      pure argon or xenon discharge and for the same ion in a mixture of argon and
      xenon. We conclude that, in our simulation, each ion reaches its own Bohm speed
      at the presheath-sheath interface.

PMID- 21867015
TI  - Three-dimensional dynamics of breakout afterburner ion acceleration using high
      contrast short-pulse laser and nanoscale targets.
AB  - Breakout afterburner (BOA) laser-ion acceleration has been demonstrated for the
      first time in the laboratory. In the BOA, an initially solid-density target
      undergoes relativistically induced transparency, initiating a period of enhanced
      ion acceleration. First-ever kinetic simulations of the BOA in three dimensions
      show that the ion beam forms lobes in the direction orthogonal to laser
      polarization and propagation. Analytic theory presented for the electron dynamics
      in the laser ponderomotive field explains how azimuthal symmetry breaks even for
      a symmetric laser intensity profile; these results are consistent with recent
      experiments at the Trident laser facility.

PMID- 21866996
TI  - First search for multijet resonances in sqrt(s) = 1.96  TeV pp collisions.
AB  - We present the first model independent search for three-jet hadronic resonances
      within multijet events in sqrt(s) = 1.96  TeV pp collisions at the Fermilab
      Tevatron using the CDF II detector. Pair production of supersymmetric gluinos and
      squarks with hadronic R-parity violating decays is employed as an example of a
      new physics benchmark for this signature. Selection criteria based on the
      kinematic properties of an ensemble of jet combinations within each event help to
      extract signal from copious QCD background. No significant excess outside the top
      quark mass window is observed in data with an integrated luminosity of 3.2  fb(
      1). We place 95% confidence level limits on the production cross section sigma(pp
      -> XX')*BR(gg -> 3  jet + 3  jet) where X, X' = g, q, or q, with q, q -> g + jet,
      as a function of gluino mass, in the range of 77  GeV/c2 to 240  GeV/c2.

PMID- 21867016
TI  - Two-dimensional visualization of growth and burst of the edge-localized filaments
      in KSTAR H-mode plasmas.
AB  - The filamentary nature and dynamics of edge-localized modes (ELMs) in the KSTAR
      high-confinement mode plasmas have been visualized in 2D via electron cyclotron
      emission imaging. The ELM filaments rotating with a net poloidal velocity are
      observed to evolve in three distinctive stages: initial linear growth, interim
      quasisteady state, and final crash. The crash is initiated by a narrow fingerlike
      perturbation growing radially from a poloidally elongated filament. The filament
      bursts through this finger, leading to fast and collective heat convection from
      the edge region into the scrape-off layer, i.e., ELM crash.

PMID- 21867017
TI  - Characterizing order in amorphous systems.
AB  - We measure and compare three correlation lengths proposed to describe the extent
      of structural order in amorphous systems. In particular, the recently proposed
      "patch correlation length" is measured as a function of temperature and fragility
      and shown to be comparable with other measures. In addition, we demonstrate that
      the patch method also allows us to characterize the symmetries of the local order
      without any a priori knowledge of it.

PMID- 21867019
TI  - Real-time measurement of stress and damage evolution during initial lithiation of
      crystalline silicon.
AB  - Crystalline to amorphous phase transformation during initial lithiation in (100)
      Si wafers is studied in an electrochemical cell with Li metal as the counter and
      reference electrode. During initial lithiation, a moving phase boundary advances
      into the wafer starting from the surface facing the lithium electrode,
      transforming crystalline Si into amorphous Li(x)Si. The resulting biaxial
      compressive stress in the amorphous layer is measured in situ, and it was
      observed to be ca. 0.5 GPa. High-resolution TEM images reveal a very sharp
      crystalline-amorphous phase boundary, with a thickness of ~1  nm. Upon
      delithiation, the stress rapidly reverses and becomes tensile, and the amorphous
      layer begins to deform plastically at around 0.5 GPa. With continued
      delithiation, the yield stress increases in magnitude, culminating in a sudden
      fracture of the amorphous layer into microfragments, and the cracks extend into
      the underlying crystalline Si.

PMID- 21867018
TI  - 3D atomic imaging by internal-detector electron holography.
AB  - A method of internal-detector electron holography is the time-reversed version of
      photoelectron holography. Using an energy-dispersive x-ray detector, an electron
      gun, and a computer-controllable sample stage, we measured a multiple-energy
      hologram of the atomic arrangement around the Ti atom in SrTiO3 by recording the
      characteristic Ti Kalpha x-ray spectra for different electron beam angles and
      wavelengths. A real-space image was obtained by using a fitting-based
      reconstruction algorithm. 3D atomic images of the elements Sr, Ti, and O in
      SrTiO3 were clearly visualized. The present work reveals that internal-detector
      electron holography has great potential for reproducing 3D atomic arrangements,
      even for light elements.

PMID- 21867020
TI  - Direct diffusion through interpenetrating networks: oxygen in titanium.
AB  - How impurity atoms move through a crystal is a fundamental and recurrent question
      in materials. The previous models of oxygen diffusion in titanium relied on
      interstitial lattice sites that were recently found to be unstable--leaving no
      consistent picture of the diffusion pathways. Using first-principles quantum
      mechanical methods, we find three oxygen interstitial sites in titanium, and
      quantify the multiple interpenetrating networks for oxygen diffusion.
      Surprisingly, all transitions contribute to diffusion.

PMID- 21867021
TI  - Theoretical and experimental evidence for a new post-cotunnite phase of titanium
      dioxide with significant optical absorption.
AB  - We report the discovery of a post-cotunnite phase of TiO2 by both density
      functional ab initio calculations and high-pressure experiments. A pressure
      induced phase transition to a hexagonal Fe2P-type structure (space group P62m)
      was predicted to occur at 161 GPa and 0 K and successfully observed by in situ
      synchrotron x-ray diffraction measurements at 210 GPa and 4000 K with a
      significant increase in opacity. This change in opacity is attributed to a
      reduction of band gap from 3.0 to 1.9 eV across the phase change. The Fe2P-type
      structure is proved to be the densest phase in major metal dioxides.

PMID- 21867022
TI  - Taming the blackbody with infrared metamaterials as selective thermal emitters.
AB  - In this Letter we demonstrate, for the first time, selective thermal emitters
      based on metamaterial perfect absorbers. We experimentally realize a narrow band
      midinfrared (MIR) thermal emitter. Multiple metamaterial sublattices further
      permit construction of a dual-band MIR emitter. By performing both emissivity and
      absorptivity measurements, we find that emissivity and absorptivity agree very
      well as predicted by Kirchhoff's law of thermal radiation. Our results directly
      demonstrate the great flexibility of metamaterials for tailoring blackbody
      emission.

PMID- 21867024
TI  - Anomalous scaling in heteroepitaxial island dynamics on Ag(100).
AB  - Diffusion and decay of alloyed Cu/Ag islands are investigated in the size range
      from 1 to 40  nm2 on Ag(100) at room temperature with fast-scanning tunneling
      microscopy and density functional theory. While islands at sizes above 7  nm2
      show the diffusion and decay behavior expected for dynamics based on single atom
      hopping, islands smaller than 4  nm2 diffuse faster and decay slower than
      predicted by standard theory. This anomalous behavior at unexpected large island
      sizes is related to a size dependent dealloying of the Cu/Ag islands.

PMID- 21867023
TI  - Design rule for colloidal crystals of DNA-functionalized particles.
AB  - We report a Monte Carlo simulation study of the phase behavior of colloids coated
      with long, flexible DNA chains. We find that an important change occurs in the
      phase diagram when the number of DNAs per colloid is decreased below a critical
      value. In this case, the triple point disappears and the condensed phase that
      coexists with the vapor is always liquid. Our simulations thus explain why, in
      the dilute solutions typically used in experiments, colloids coated with a small
      number of DNA strands cannot crystallize. We understand this behavior in terms of
      the discrete nature of DNA binding.

PMID- 21867025
TI  - Face-dependent bond lengths in molecular chemisorption: the formate species on
      Cu(111) and Cu(110).
AB  - Many previous structural studies of molecular adsorbates on metal surfaces
      indicate that the local coordination and bonding is closely similar to that in
      organometallic compounds, implying that the metallic substrate has no significant
      influence. Here we show that such an influence is detectable for one model
      system, namely, the formate species, HCOO, adsorbed on the atomically rough and
      smooth (110) and (111) surfaces of Cu, leading to a statistically significant
      difference (0.09+/-0.05  A) in the Cu-O chemisorption bond length. The effect is
      reproduced in density functional theory calculations.

PMID- 21867027
TI  - Snake states along graphene p-n junctions.
AB  - We investigate transport in locally gated graphene devices, where carriers are
      injected and collected along, rather than across, the gate edge. Tuning densities
      into the p-n regime significantly reduces resistance along the p-n interface,
      while resistance across the interface increases. This provides an experimental
      signature of snake states, which zigzag along the p-n interface and remain stable
      as applied perpendicular magnetic field approaches zero. Snake states appear as a
      peak in transverse resistance measured along the p-n interface. The generic role
      of snake states in disordered graphene is also discussed.

PMID- 21867026
TI  - Scaling behavior of the spin pumping effect in ferromagnet-platinum bilayers.
AB  - We systematically measured the dc voltage V(ISH) induced by spin pumping together
      with the inverse spin Hall effect in ferromagnet-platinum bilayer films. In all
      our samples, comprising ferromagnetic 3d transition metals, Heusler compounds,
      ferrite spinel oxides, and magnetic semiconductors, V(ISH) invariably has the
      same polarity, and scales with the magnetization precession cone angle. These
      findings, together with the spin mixing conductance derived from the experimental
      data, quantitatively corroborate the present theoretical understanding of spin
      pumping in combination with the inverse spin Hall effect.

PMID- 21867028
TI  - Laserlike vibrational instability in rectifying molecular conductors.
AB  - We study the damping of molecular vibrations due to electron-hole pair
      excitations in donor-acceptor (D-A) type molecular rectifiers. At finite voltage
      additional nonequilibrium electron-hole pair excitations involving both
      electrodes become possible, and contribute to the stimulated emission and
      absorption of phonons. We point out a generic mechanism for D-A molecules, where
      the stimulated emission can dominate beyond a certain voltage due to the inverted
      position of the D and A quantum resonances. This leads to current-driven
      amplification (negative damping) of the phonons similar to laser action. We
      investigate the effect in realistic molecular rectifier structures using first
      principles calculations.

PMID- 21867029
TI  - Quantum interference and decoherence in single-molecule junctions: how vibrations
      induce electrical current.
AB  - Quantum interference and decoherence in single-molecule junctions is analyzed
      employing a nonequilibrium Green's function approach. Electrons tunneling through
      quasidegenerate states of a molecular junction exhibit interference effects. We
      show that electronic-vibrational coupling, inherent to any molecular junction,
      strongly quenches such interference effects. This decoherence mechanism may cause
      significantly larger electrical currents and is particularly pronounced if the
      junction is vibrationally highly excited, e.g., due to inelastic processes in the
      resonant transport regime.

PMID- 21867030
TI  - Long-range superharmonic Josephson current.
AB  - We consider a long superconductor-ferromagnet-superconductor junction with one
      spin-active region. It is shown that an odd number of Cooper pairs cannot have a
      long-range propagation when there is only one spin-active region. When the
      temperature is much lower than the Thouless energy, the coherent transport of two
      Cooper pairs becomes the dominant process and the superharmonic current-phase
      relation is obtained (I ? sin2phi).

PMID- 21867031
TI  - Antiferromagnetic spin fluctuations and unconventional nodeless superconductivity
      in an iron-based new superconductor (Ca4Al2O(6-y))(Fe2As2): 75As nuclear
      quadrupole resonance study.
AB  - We report 75As nuclear quadrupole resonance studies on (Ca4Al2O(6-y))(Fe2As2)
      with T(c) = 27  K. Measurement of nuclear-spin-relaxation rate 1/T1 has revealed
      a significant development of two-dimensional antiferromagnetic spin fluctuations
      down to T(c) in association with the smallest As-Fe-As bond angle. Below T(c),
      the temperature dependence of 1/T1 without any trace of the coherence peak is
      well accounted for by a nodeless s(+/-)-wave multiple-gaps model. From the fact
      that its T(c) is comparable to T(c) = 28  K in the optimally doped LaFeAsO(1-y)
      in which antiferromagnetic spin fluctuations are not dominant, we remark that
      antiferromagnetic spin fluctuations are not a unique factor for enhancing T(c)
      among Fe-based superconductors, but a condition for optimizing superconductivity
      should be addressed from the lattice structure point of view.

PMID- 21867032
TI  - Reconstructed Fermi surface of underdoped Bi2Sr2CaCu2O(8+delta) cuprate
      superconductors.
AB  - The Fermi surface topologies of underdoped samples of the high-T(c)
      superconductor Bi2Sr2CaCu2O(8+delta) have been measured with angle resolved
      photoemission. By examining thermally excited states above the Fermi level, we
      show that the observed Fermi surfaces in the pseudogap phase are actually
      components of fully enclosed hole pockets. The spectral weight of these pockets
      is vanishingly small at the magnetic zone boundary, creating the illusion of
      Fermi "arcs." The area of the pockets as measured in this study is consistent
      with the doping level, and hence carrier density, of the samples measured.
      Furthermore, the shape and area of the pockets is well reproduced by
      phenomenological models of the pseudogap phase as a spin liquid.

PMID- 21867033
TI  - Magnetoelastic quantum fluctuations and phase transitions in the iron
      superconductors.
AB  - We examine the relevance of magnetoelastic coupling to describe the complex
      magnetic and structural behavior of the different classes of the iron
      superconductors. We model the system as a two-dimensional metal whose magnetic
      excitations interact with the distortions of the underlying square lattice. Going
      beyond the mean field, we find that quantum fluctuation effects can explain two
      unusual features of these materials that have attracted considerable attention:
      first, why iron telluride orders magnetically at a non-nesting wave vector
      (pi/2,pi/2) and not at the nesting wave vector (pi,0) as in the iron arsenides,
      even though the nominal band structures of both these systems are similar, and
      second, why the (pi,0) magnetic transition in the iron arsenides is often
      preceded by an orthorhombic structural transition. These are robust properties of
      the model, independent of microscopic details, and they emphasize the importance
      of the magnetoelastic interaction.

PMID- 21867034
TI  - Electric field control of valence tautomeric interconversion in cobalt dioxolene.
AB  - We demonstrate that the critical temperature for valence tautomeric
      interconversion in cobalt dioxolene complexes can be significantly changed when a
      static electric field is applied to the molecule. This is achieved by effectively
      manipulating the redox potential of the metallic acceptor forming the molecule.
      Importantly, our accurate density functional theory calculations demonstrate that
      already a field of 0.1  V/nm, achievable in Stark spectroscopy experiments, can
      produce a change in the critical temperature for the interconversion of 20 K. Our
      results indicate a new way for switching on and off the magnetism in a magnetic
      molecule. This offers the unique chance of controlling magnetism at the atomic
      scale by electrical means.

PMID- 21867035
TI  - Efficient spin injector scheme based on Heusler materials.
AB  - We present a rational design scheme intended to provide stable high spin
      polarization at the interfaces of the magnetoresistive junctions by fulfilling
      the criteria of structural and chemical compatibilities at the interface. This
      can be realized by joining the semiconducting and half-metallic Heusler materials
      with similar structures. The present first-principles calculations verify that
      the interface remains half-metallic if the nearest interface layers effectively
      form a stable Heusler material with the properties intermediately between the
      surrounding bulk parts. This leads to a simple rule for selecting the proper
      combinations.

PMID- 21867036
TI  - Zero- and low-temperature behavior of the two-dimensional +/-J Ising spin glass.
AB  - Scaling arguments and precise simulations are used to study the square lattice +/
      J Ising spin glass, a prototypical model for glassy systems. Droplet theory
      explains, and our numerical results show, entropically stabilized long-range spin
      glass order at zero temperature, which resembles the energetic stabilization of
      long-range order in higher-dimensional models at finite temperature. At low
      temperature, a temperature-dependent crossover length scale is used to predict
      the power-law dependence on temperature of the heat capacity and clarify the
      importance of disorder distributions.

PMID- 21867037
TI  - Spin-glass transition in bond-disordered Heisenberg antiferromagnets coupled with
      local lattice distortions on a pyrochlore lattice.
AB  - Motivated by puzzling characteristics of spin-glass transitions widely observed
      in pyrochlore-based frustrated materials, we investigate the effects of coupling
      to local lattice distortions in a bond-disordered antiferromagnet on the
      pyrochlore lattice by extensive Monte Carlo simulations. We show that the spin
      glass transition temperature T(f) is largely enhanced by the spin-lattice
      coupling and, furthermore, becomes almost independent of Delta in a wide range of
      the disorder strength Delta. The critical property of the spin-glass transition
      is indistinguishable from that of the canonical Heisenberg spin glass in the
      entire range of Delta. These peculiar behaviors are ascribed to a modification of
      the degenerate manifold from a continuous to semidiscrete one by spin-lattice
      coupling.

PMID- 21867038
TI  - Magnonic crystal as a medium with tunable disorder on a periodical lattice.
AB  - We show that periodic magnetic nanostructures represent a perfect system for
      studying excitations on disordered periodical lattices because of the possibility
      of controlled variation of the degree of disorder by varying the applied magnetic
      field. Magnetic force microscopy images and ferromagnetic resonance (FMR) data
      collected inside minor hysteresis loops for a periodic array of Permalloy
      nanowires were used to demonstrate correlation between the type of FMR response
      and the degree of disorder of the magnetic ground state.

PMID- 21867039
TI  - Observation of long spin-relaxation times in bilayer graphene at room
      temperature.
AB  - We report on the first systematic study of spin transport in bilayer graphene
      (BLG) as a function of mobility, minimum conductivity, charge density, and
      temperature. The spin-relaxation time tau(s) scales inversely with the mobility
      MU of BLG samples both at room temperature (RT) and at low temperature (LT). This
      indicates the importance of D'yakonov-Perel' spin scattering in BLG. Spin
      relaxation times of up to 2 ns at RT are observed in samples with the lowest
      mobility. These times are an order of magnitude longer than any values previously
      reported for single-layer graphene (SLG). We discuss the role of intrinsic and
      extrinsic factors that could lead to the dominance of D'yakonov-Perel' spin
      scattering in BLG. In comparison to SLG, significant changes in the carrier
      density dependence of tau(s) are observed as a function of temperature.

PMID- 21867040
TI  - Spin relaxation in single-layer and bilayer graphene.
AB  - We investigate spin relaxation in graphene spin valves and observe strongly
      contrasting behavior for single-layer graphene (SLG) and bilayer graphene (BLG).
      In SLG, the spin lifetime (tau(s)) varies linearly with the momentum scattering
      time (tau(p)) as carrier concentration is varied, indicating the dominance of
      Elliot-Yafet (EY) spin relaxation at low temperatures. In BLG, tau(s) and tau(p)
      exhibit an inverse dependence, which indicates the dominance of Dyakonov-Perel
      spin relaxation at low temperatures. The different behavior is due to enhanced
      screening and/or reduced surface sensitivity of BLG, which greatly reduces the
      impurity-induced EY spin relaxation.

PMID- 21867041
TI  - Unconventional magnetism in a nitrogen-containing analog of cupric oxide.
AB  - We have investigated the magnetic properties of CuNCN, the first nitrogen-based
      analog of cupric oxide CuO. Our muon-spin relaxation, nuclear magnetic resonance,
      and electron-spin resonance studies reveal that classical magnetic ordering is
      absent down to the lowest temperatures. However, a large enhancement of spin
      correlations and an unexpected inhomogeneous magnetism have been observed below
      80 K. We attribute this to a peculiar fragility of the electronic state against
      weak perturbations due to geometrical frustration, which selects between
      competing spin-liquid and more conventional frozen states.

PMID- 21867042
TI  - Enhanced photoinduced desorption from metal nanoparticles by photoexcitation of
      confined hot electrons using femtosecond laser pulses.
AB  - Strong fluence dependence of photodesorption cross sections is observed in
      femtosecond laser photodesorption of NO from (NO)2 on silver nanoparticles, in
      contrast to femtosecond photodesorption on bulk metals. The time scale of
      excitation buildup is found to be equal or less than the pulse duration of ~100 
      fs; NO translational energies are independent of fluence and pulse duration. We
      propose a nanoparticle-specific nonlinear mechanism in which, due to confinement,
      strongly nonthermal hot-electron distributions are maintained during the
      femtosecond pulses, enhancing the normal desorption pathway.

PMID- 21867043
TI  - Electron-nuclear dynamics in a quantum dot under nonunitary electron control.
AB  - We introduce a method for solving the problem of an externally controlled
      electron spin in a quantum dot interacting with host nuclei via the hyperfine
      interaction. Our method accounts for generalized (nonunitary) evolution effected
      by external controls and the environment, such as coherent lasers combined with
      spontaneous emission. As a concrete example, we develop the microscopic theory of
      the dynamics of nuclear-induced frequency focusing as first measured in Science
      317, 1896 (2007); we find that the nuclear relaxation rates are several orders of
      magnitude faster than those quoted in that work.

PMID- 21867044
TI  - Dense granular flow around a penetrating object: experiment and hydrodynamic
      model.
AB  - We present in this Letter experimental results on the bidimensional flow field
      around a cylinder penetrating into dense granular matter, together with drag
      force measurements. A hydrodynamic model based on extended kinetic theory for
      dense granular flow reproduces well the flow localization close to the cylinder
      and the corresponding scalings of the drag force, which is found to not depend on
      velocity, but linearly on the pressure and on the cylinder diameter and weakly on
      the grain size. Such a regime is found to be valid at a low enough "granular"
      Reynolds number.

PMID- 21867045
TI  - Liquid-gas phase separation in confined vibrated dry granular matter.
AB  - A new phase transition is observed experimentally in a dry granular gas subject
      to vertical vibration between two horizontal plates. Molecular dynamics
      simulations of this system allow us to investigate the observed phase separation
      in detail. We find a high-density, low temperature liquid, coexisting with a low
      density, high temperature gas moving coherently. The importance of the coherent
      motion for phase separation is investigated using frequency modulation.

PMID- 21867046
TI  - Multiplexing biochemical signals.
AB  - In this Letter we show that living cells can multiplex biochemical signals, i.e.,
      transmit multiple signals through the same signaling pathway simultaneously, and
      yet respond to them very specifically. We demonstrate how two binary input
      signals can be encoded in the concentration of a common signaling protein, which
      is then decoded such that each of the two output signals provides reliable
      information about one corresponding input. Under biologically relevant conditions
      the network can reach the maximum amount of information that can be transmitted,
      which is 2 bits.

PMID- 21867047
TI  - Determination of the defining boundary in nuclear magnetic resonance diffusion
      experiments.
AB  - While nuclear magnetic resonance diffusion experiments are widely used to resolve
      structures confining the diffusion process, it has been elusive whether they can
      exactly reveal these structures. This question is closely related to x-ray
      scattering and to Kac's "hear the drum" problem. Although the shape of the drum
      is not "hearable," we show that the confining boundary of closed pores can indeed
      be detected using modified Stejskal-Tanner magnetic field gradients that preserve
      the phase information and enable imaging of the average pore in a porous medium
      with a largely increased signal-to-noise ratio.

PMID- 21867048
TI  - Weber's law for biological responses in autocatalytic networks of chemical
      reactions.
AB  - Biological responses often obey Weber's law, according to which the magnitude of
      the response depends only on the fold change in the external input. In this
      study, we demonstrate that a system involving a simple autocatalytic reaction
      shows such a response when a chemical is slowly synthesized by the reaction from
      a faster influx process. We also show that an autocatalytic reaction process
      occurring in series or in parallel can obey Weber's law with an oscillatory
      adaptive response. Considering the simplicity and ubiquity of the autocatalytic
      process, our proposed mechanism is thought to be commonly observed in biological
      reactions.

PMID- 21867049
TI  - Nonthermal statistics in isolated quantum spin clusters after a series of
      perturbations.
AB  - We show numerically that a finite isolated cluster of interacting spins 1/2
      exhibits a surprising nonthermal statistics when subjected to a series of small
      nonadiabatic perturbations by an external magnetic field. The resulting
      occupations of energy eigenstates are significantly higher than the thermal ones
      on both the low and the high ends of the energy spectra. This behavior
      semiquantitatively agrees with the statistics predicted for the so-called
      "quantum microcanonical" ensemble, which includes all possible quantum
      superpositions with a given energy expectation value. Our findings also indicate
      that the eigenstates of the perturbation operators are generically localized in
      the energy basis of the unperturbed Hamiltonian. This kind of localization
      possibly protects the thermal behavior in the macroscopic limit.

PMID- 21867050
TI  - Stability of spin-orbit coupled Fermi gases with population imbalance.
AB  - We use the self-consistent mean-field theory to analyze the effects of Rashba
      type spin-orbit coupling (SOC) on the ground-state phase diagram of population
      imbalanced Fermi gases throughout the BCS-Bose-Einstein condensate evolution. We
      find that the SOC and population imbalance are counteracting, and that this
      competition tends to stabilize the uniform superfluid phase against the phase
      separation. However, we also show that the SOC stabilizes (destabilizes) the
      uniform superfluid phase against the normal phase for low (high) population
      imbalances. In addition, we find topological quantum phase transitions associated
      with the appearance of momentum-space regions with zero quasiparticle energies,
      and study their signatures in the momentum distribution.

PMID- 21867051
TI  - Charge qubit purification by an electronic feedback loop.
AB  - We propose the manipulation of an isolated qubit by a simple instantaneous closed
      loop feedback scheme in which a time-dependent electronic detector current is
      directly back-coupled into qubit parameters. As a specific detector model, we
      employ a capacitively coupled single-electron transistor. We demonstrate the
      stabilization of pure delocalized qubit states above a critical detector-qubit
      coupling. This electronic purification is independent of the initial qubit state
      and is accomplished after few electron jumps through the detector. Our simple
      scheme can be used for the efficient and robust initialization of solid-state
      qubits in quantum computational algorithms at arbitrary temperatures.

PMID- 21867052
TI  - Device-independent certification of entangled measurements.
AB  - We present a device-independent protocol to test if a given black-box measurement
      device is entangled, that is, has entangled eigenstates. Our scheme involves
      three parties and is inspired by entanglement swapping; the test uses the Clauser
      Horne-Shimony-Holt Bell inequality, checked between each pair of parties. In the
      case where all particles are qubits, we characterize quantitatively the deviation
      of the measurement device from a perfect Bell-state measurement.

PMID- 21867053
TI  - Scalable spin amplification with a gain over a hundred.
AB  - We propose a scalable and practical implementation of spin amplification which
      does not require individual addressing nor a specially tailored spin network. We
      have demonstrated a gain of 140 in a solid-state nuclear spin system of which the
      spin polarization has been increased to 0.12 using dynamic nuclear polarization
      with photoexcited triplet electron spins. Spin amplification scalable to a higher
      gain opens the door to the single spin measurement for a readout of quantum
      computers as well as practical applications of nuclear magnetic resonance
      spectroscopy to infinitesimal samples which have been concealed by thermal noise.

PMID- 21867054
TI  - Quantum decoherence of single-photon counters.
AB  - The interaction of a quantum system with the environment leads to the so-called
      quantum decoherence. Beyond its fundamental significance, the understanding and
      the possible control of this dynamics in various scenarios is a key element for
      mastering quantum information processing. Here we report the quantitative probing
      of what can be called the quantum decoherence of detectors, a process reminiscent
      of the decoherence of quantum states in the presence of coupling with a
      reservoir. We demonstrate how the quantum features of two single-photon counters
      vanish under the influence of a noisy environment. We thereby experimentally
      witness the transition between the full-quantum operation of the measurement
      device to the "semi-classical regime", described by a positive Wigner function.
      The exact border between these two regimes is explicitely determined and measured
      experimentally.

PMID- 21867055
TI  - "Negative" backaction noise in interferometric detection of a microlever.
AB  - Interferometric detection of mirror displacements is intrinsically limited by
      laser shot noise. In practice, however, it is often limited by thermal noise.
      Here we report on an experiment performed at the liquid helium temperature to
      overcome the thermal noise limitation and investigate the effect of classical
      laser noise on a microlever that forms a Fabry-Perot cavity with an optical
      fiber. The spectral noise densities show a region of "negative" contribution of
      the backaction noise close to the resonance frequency. We interpret this noise
      reduction as a coherent coupling of the microlever to the laser intensity noise.
      This optomechanical effect could be used to improve the detection sensitivity as
      discussed in proposals going beyond the standard quantum limit.

PMID- 21867056
TI  - Area-angular-momentum inequality for axisymmetric black holes.
AB  - We prove the local inequality A>=8pi|J|, where A and J are the area and angular
      momentum of any axially symmetric closed stable minimal surface in an axially
      symmetric maximal initial data. From this theorem it is proved that the
      inequality is satisfied for any surface on complete asymptotically flat maximal
      axisymmetric data. In particular it holds for marginal or event horizons of black
      holes. Hence, we prove the validity of this inequality for all dynamical (not
      necessarily near equilibrium) axially symmetric black holes.

PMID- 21867057
TI  - Gravitational waves and neutrino emission from the merger of binary neutron
      stars.
AB  - Numerical simulations for the merger of binary neutron stars are performed in
      full general relativity incorporating a finite-temperature (Shen's) equation of
      state (EOS) and neutrino cooling for the first time. It is found that for this
      stiff EOS, a hypermassive neutron star (HMNS) with a long lifetime (?10  ms) is
      the outcome for the total mass ?3.0M(?). It is shown that the typical total
      neutrino luminosity of the HMNS is ~3-8*10(53)  erg/s and the effective amplitude
      of gravitational waves from the HMNS is 4-6*10(-22) at f=2.1-2.5  kHz for a
      source distance of 100 Mpc. We also present the neutrino luminosity curve when a
      black hole is formed for the first time.

PMID- 21867058
TI  - Rotation, the equivalence principle, and the Gravity Probe B experiment.
AB  - The ultraprecise Gravity Probe B experiment measured the frame-dragging effect
      and geodetic precession on four quartz gyros. We use this result to test WEP II
      (weak equivalence principle II) which includes rotation in the universal free
      fall motion. The free-fall Eotvos parameter eta for a rotating body is <=10(-11)
      with a four-order improvement over previous results. The anomalous torque per
      unit angular momentum parameter lambda is constrained to (-0.05+/-3.67)*10(-15) 
      s(-1), (0.24+/-0.98)*10(-15)  s(-1), and (0+/-3.6)*10(-13) s(-1), respectively,
      in the directions of geodetic effect, frame-dragging effect, and angular momentum
      axis; the dimensionless frequency-dependence parameter kappa is constrained to
      (1.75+/-4.96)*10(-17), (1.80+/-1.34)*10(-17), and (0+/-3)*10(-14), respectively.

PMID- 21867059
TI  - Search for light dark matter in XENON10 data.
AB  - We report results of a search for light (?10  GeV) particle dark matter with the
      XENON10 detector. The event trigger was sensitive to a single electron, with the
      analysis threshold of 5 electrons corresponding to 1.4 keV nuclear recoil energy.
      Considering spin-independent dark matter-nucleon scattering, we exclude cross
      sections sigma(n)>7*10(-42)  cm(2), for a dark matter particle mass m(chi)=7 
      GeV. We find that our data strongly constrain recent elastic dark matter
      interpretations of excess low-energy events observed by CoGeNT and CRESST-II, as
      well as the DAMA annual modulation signal.

PMID- 21867062
TI  - Sign of kurtosis near the QCD critical point.
AB  - We point out that the quartic cumulant (and kurtosis) of the order parameter
      fluctuations is universally negative when the critical point is approached on the
      crossover side of the phase separation line. As a consequence, the kurtosis of a
      fluctuating observable, such as, e.g., proton multiplicity, may become smaller
      than the value given by independent Poisson statistics. We discuss implications
      for the beam energy scan program at RHIC at BNL.

PMID- 21867064
TI  - Chiral magnetic wave at finite baryon density and the electric quadrupole moment
      of the quark-gluon plasma.
AB  - The chiral magnetic wave is a gapless collective excitation of quark-gluon plasma
      in the presence of an external magnetic field that stems from the interplay of
      chiral magnetic and chiral separation effects; it is composed of the waves of the
      electric and chiral charge densities coupled by the axial anomaly. We consider a
      chiral magnetic wave at finite baryon density and find that it induces the
      electric quadrupole moment of the quark-gluon plasma produced in heavy ion
      collisions: the "poles" of the produced fireball (pointing outside of the
      reaction plane) acquire additional positive electric charge, and the "equator"
      acquires additional negative charge. We point out that this electric quadrupole
      deformation lifts the degeneracy between the elliptic flows of positive and
      negative pions leading to v(2)(pi(+))<v(2)(pi(-)), and estimate the magnitude of
      the effect.

PMID- 21867065
TI  - First observation of two-electron one-photon transitions in single-photon K-shell
      double ionization.
AB  - Experimental evidence for the correlated two-electron one-photon transitions (1s(
      2)->2s(-1)2p(-1)) following single-photon K-shell double ionization is reported.
      The double K-shell vacancy states in solid Mg, Al, and Si were produced by means
      of monochromatized synchrotron radiation, and the two-electron one-photon
      radiative transitions were observed by using a wavelength dispersive
      spectrometer. The two-electron one-photon transition energies and the branching
      ratios of the radiative one-electron to two-electron transitions were determined
      and compared to available perturbation theory predictions and configuration
      interaction calculations.

PMID- 21867067
TI  - Higher-order Poincare sphere, stokes parameters, and the angular momentum of
      light.
AB  - A higher-order Poincare sphere and Stokes parameter representation of the higher
      order states of polarization of vector vortex beams that includes radial and
      azimuthal polarized cylindrical vector beams is presented. The higher-order
      Poincare sphere is constructed by naturally extending the Jones vector basis of
      plane wave polarization in terms of optical spin angular momentum to the total
      optical angular momentum that includes higher dimensional orbital angular
      momentum. The salient properties of this representation are illustrated by its
      ability to describe the higher-order modes of optical fiber waveguides, more
      exotic vector beams, and a higher-order Pancharatnam-Berry geometric phase.

PMID- 21867060
TI  - Search for new dielectron resonances and Randall-Sundrum gravitons at the
      collider detector at Fermilab.
AB  - A search for new dielectron-mass resonances using data recorded by the CDF II
      detector and corresponding to an integrated luminosity of 5.7  fb(-1) is
      presented. No significant excess over the expected standard model prediction is
      observed. In this data set, an event with the highest dielectron mass ever
      observed (960  GeV/c(2)) was recorded. The results are interpreted in the Randall
      Sundrum (RS) model. Combined with the 5.4  fb(-1) diphoton analysis, the RS
      graviton lower-mass limit for the coupling k/M-(Pl)=0.1 is 1058  GeV/c(2), making
      it the strongest limit to date.

PMID- 21867066
TI  - Three-electron interatomic Coulombic decay from the inner-valence double-vacancy
      states in NeAr.
AB  - We have unambiguously identified interatomic Coulombic decay in NeAr from the
      inner-valence double-vacancy state Ne-Ar(2+)(3s(-2)) to outer-valence triple
      vacancy states Ne(+)(2p(-1))-Ar(2+)(3p(-2)) by momentum-resolved electron-ion
      multicoincidence. This is the first observation of interatomic Coulombic decay
      where three electrons (3e) participate. The results suggest that this 3e
      interatomic Coulombic decay is significantly faster than other competing
      processes like fluorescence decay and charge transfer via curve crossing.

PMID- 21867068
TI  - Dispersive photon blockade in a superconducting circuit.
AB  - Mediated photon-photon interactions are realized in a superconducting coplanar
      waveguide cavity coupled to a superconducting charge qubit. These nonresonant
      interactions blockade the transmission of photons through the cavity. This so
      called dispersive photon blockade is characterized by measuring the total
      transmitted power while varying the energy spectrum of the photons incident on
      the cavity. A staircase with four distinct steps is observed and can be
      understood in an analogy with electron transport and the Coulomb blockade in
      quantum dots. This work differs from previous efforts in that the cavity-qubit
      excitations retain a photonic nature rather than a hybridization of qubit and
      photon and provides the needed tolerance to disorder for future condensed matter
      experiments.

PMID- 21867069
TI  - Single-photon-level quantum memory at room temperature.
AB  - Room-temperature, easy-to-operate quantum memories are essential building blocks
      for future long distance quantum information networks operating on an
      intercontinental scale, because devices like quantum repeaters, based on quantum
      memories, will have to be deployed in potentially remote, inaccessible locations.
      Here we demonstrate controllable, broadband and efficient storage and retrieval
      of weak coherent light pulses at the single-photon level in warm atomic cesium
      vapor using the robust far off-resonant Raman memory scheme. We show that the
      unconditional noise floor of this technically simple quantum memory is low enough
      to operate in the quantum regime, even in a room-temperature environment.

PMID- 21867070
TI  - Bragg scattering of light in vacuum structured by strong periodic fields.
AB  - Elastic scattering of laser radiation due to vacuum polarization by spatially
      modulated strong electromagnetic fields is considered. The Bragg interference
      arising at a specific impinging direction of the probe wave concentrates the
      scattered light in specular directions. The interference maxima are enhanced with
      respect to the usual vacuum polarization effect proportional to the square of the
      number of modulation periods within the interaction region. The Bragg scattering
      can be employed to detect the vacuum polarization effect in a setup of multiple
      crossed superstrong laser beams with parameters envisaged in the future Extreme
      Light Infrastructure.

PMID- 21867071
TI  - Deterministic optical rogue waves.
AB  - Experimental observations of rare giant pulses or rogue waves were done in the
      output intensity of an optically injected semiconductor laser. The long-tailed
      probability distribution function of the pulse amplitude displays clear non
      Gaussian features that confirm the rogue wave character of the intensity
      pulsations. Simulations of a simple rate equation model show good qualitative
      agreement with the experiments and provide a framework for understanding the
      observed extreme amplitude events as the result of a deterministic nonlinear
      process.

PMID- 21867061
TI  - Limits on anomalous trilinear gauge couplings in Zgamma events from pp-
      collisions at ?s=1.96  TeV.
AB  - Using Zgamma candidate events collected by the CDF detector at the Tevatron
      Collider, we search for potential anomalous (non-standard-model) couplings
      between the Z boson and the photon. Zgamma couplings vanish at tree level and are
      heavily suppressed at higher orders; hence any evidence of couplings indicates
      new physics. Measurements are performed using data corresponding to an integrated
      luminosity of 4.9  fb(-1) in the Z->nunu- decay channel and 5.1  fb(-1) in the Z
      >l(+)l(-) (l=MU, e) decay channels. The combination of these measurements
      provides the most stringent limits to date on Zgamma trilinear gauge couplings.
      Using an energy scale of Lambda=1.5  TeV to allow for a direct comparison with
      previous measurements, we find limits on the CP-conserving parameters that
      describe Zgamma couplings to be |h(3)(gamma,Z)|<0.022 and |h(4)(gamma,Z)|<0.0009.
      These results are consistent with standard model predictions.

PMID- 21867072
TI  - Inner composition alignment for inferring directed networks from short time
      series.
AB  - Identifying causal links (couplings) is a fundamental problem that facilitates
      the understanding of emerging structures in complex networks. We propose and
      analyze inner composition alignment-a novel, permutation-based asymmetric
      association measure to detect regulatory links from very short time series,
      currently applied to gene expression. The measure can be used to infer the
      direction of couplings, detect indirect (superfluous) links, and account for
      autoregulation. Applications to the gene regulatory network of E. coli are
      presented.

PMID- 21867073
TI  - Spontaneous transition of turbulent flames to detonations in unconfined media.
AB  - A deflagration-to-detonation transition (DDT) can occur in environments ranging
      from experimental and industrial systems to astrophysical thermonuclear (type Ia)
      supernovae explosions. Substantial progress has been made in explaining the
      nature of DDT in confined systems with walls, internal obstacles, or preexisting
      shocks. It remains unclear, however, whether DDT can occur in unconfined media.
      Here we use direct numerical simulations (DNS) to show that for high enough
      turbulent intensities unconfined, subsonic, premixed, turbulent flames are
      inherently unstable to DDT. The associated mechanism, based on the nonsteady
      evolution of flames faster than the Chapman-Jouguet deflagrations, is
      qualitatively different from the traditionally suggested spontaneous reaction
      wave model. Critical turbulent flame speeds, predicted by this mechanism for the
      onset of DDT, are in agreement with DNS results.

PMID- 21867074
TI  - Neoclassical toroidal viscosity calculations in tokamaks using a deltaf Monte
      Carlo simulation and their verifications.
AB  - Neoclassical toroidal viscosities (NTVs) in tokamaks are investigated using a
      deltaf Monte Carlo simulation, and are successfully verified with a combined
      analytic theory over a wide range of collisionality. A Monte Carlo simulation has
      been required in the study of NTV since the complexities in guiding-center orbits
      of particles and their collisions cannot be fully investigated by any means of
      analytic theories alone. Results yielded the details of the complex NTV
      dependency on particle precessions and collisions, which were predicted roughly
      in a combined analytic theory. Both numerical and analytic methods can be
      utilized and extended based on these successful verifications.

PMID- 21867075
TI  - Collisionless bounce resonance heating in dual-frequency capacitively coupled
      plasmas.
AB  - We present the experimental evidence of the collisionless electron bounce
      resonance heating (BRH) in low-pressure dual-frequency capacitively coupled
      plasmas. In capacitively coupled plasmas at low pressures when the discharge
      frequency and gap satisfy a certain resonant condition, the high energy beamlike
      electrons can be generated by fast sheath expansion, and heated by the two
      sheaths coherently, thus the BRH occurs. By using a combined measurement of a
      floating double probe and optical emission spectroscopy, we demonstrate the
      effect of BRH on plasma properties, such as plasma density and light emission,
      especially in dual-frequency discharges.

PMID- 21867076
TI  - Generation of a sheared plasma rotation by emission, propagation, and absorption
      of drift wave packets.
AB  - Collisional electron drift wave turbulence generates drift wave packet structures
      with density and vorticity fluctuations in the central plasma pressure gradient
      region of a linear plasma device. Tracking these packets reveals that they follow
      an outward directed spiral-shaped trajectory in the (r,theta) plane, are
      azimuthally stretched, and develop anisotropy as they approach an axisymmetric,
      radially sheared azimuthal flow located at the plasma boundary. Nonlinear energy
      transfer measurements and time-delay analysis confirm that structure absorption
      amplifies the sheared flow. Similar mechanisms likely operate at the edge of
      confined toroidal plasmas and should lead to the amplification of sheared flows
      at the boundary of these devices as well.

PMID- 21867077
TI  - High-frequency coherent edge fluctuations in a high-pedestal-pressure quiescent H
      mode plasma.
AB  - A set of high frequency coherent (HFC) modes (f=80-250 kHz) is observed with beam
      emission spectroscopy measurements of density fluctuations in the pedestal of a
      strongly shaped quiescent H-mode plasma on DIII-D, with characteristics predicted
      for kinetic ballooning modes (KBM): propagation in the ion-diamagnetic drift
      direction; a frequency near 0.2-0.3 times the ion-diamagnetic frequency; inferred
      toroidal mode numbers of n~10-25; poloidal wave numbers of k(theta)~0.17-0.4 cm(
      1); and high measured decorrelation rates (tau(c)(-1)~omega(s)~0.5*10(6) s(-1)).
      Their appearance correlates with saturation of the pedestal pressure.

PMID- 21867078
TI  - Nanosecond dynamics of ferroelectric/dielectric superlattices.
AB  - The nanosecond response of a PbTiO(3)/SrTiO(3) ferroelectric/dielectric
      superlattice to applied electric fields is closely linked to the dynamics of
      striped domains of the remnant polarization. The intensity of domain satellite
      reflections observed with time-resolved x-ray microdiffraction decays in 5-100 ns
      depending on the magnitude of the electric field. The piezoelectric response of
      the superlattice within stripe domains is strongly suppressed due to
      electromechanical clamping between adjacent regions of opposite polarization.
      Regions of the superlattice that have been switched into a uniform polarization
      state by the applied electric field, however, exhibit piezoelectricity during the
      course of the switching process. We propose a switching model different from
      previous models of the switching of superlattices, based instead on a spatially
      heterogeneous transformation between striped and uniform polarization states.

PMID- 21867079
TI  - Dynamically stabilized growth of polar oxides: the case of MgO(111).
AB  - By using MgO(111) as a model system for polar oxide film growth, we show by first
      principles calculations that H acts as a surfactant, i.e., the H changes its
      position and bonding during the growth process, remaining in the surface region.
      Continuous presence of H during the growth of MgO(111) film efficiently removes
      the microscopic dipole moment, thus enabling the growth of perfect fcc-ordered
      MgO(111) films. These theoretical predictions are confirmed experimentally by
      molecular beam epitaxy single crystal growth of MgO(111) on SiC(0001).

PMID- 21867080
TI  - Electrostriction at the LaAlO3/SrTiO3 interface.
AB  - We present a direct comparison between experimental data and ab initio
      calculations for the electrostrictive effect in the polar LaAlO(3) layer grown on
      SrTiO(3) substrates. From the structural data, a complete screening of the
      LaAlO(3) dipole field is observed for film thicknesses between 6 and 20 uc. For
      thinner films, an expansion of the c axis of 2% matching the theoretical
      predictions for an electrostrictive effect is observed experimentally.

PMID- 21867081
TI  - Block spin ground state and three-dimensionality of (K,Tl)(y)Fe(1.6)Se2.
AB  - The magnetic properties and electronic structure of (K,Tl)(y)Fe(1.6)Se(2) is
      studied using first-principles calculations. The ground state is checkerboard
      antiferromagnetically coupled blocks of the minimal Fe(4) squares, with a large
      block-spin moment ~11.2 MU(B). The magnetic interactions could be modeled with a
      simple spin model involving both the inter- and intrablock, as well as the
      nearest-neighbor and next-nearest-neighbor couplings. The calculations also
      suggest a metallic ground state except for y=0.8 where a band gap ~400-550 meV
      opens, showing an antiferromagnetic insulator ground state for
      (K,Tl)(0.8)Fe(1.6)Se(2). The electronic structure of the metallic
      (K,Tl)(y)Fe(1.6)Se(2) is highly three dimensional with unique Fermi surface
      structure and topology. These features indicate that the Fe-vacancy ordering is
      crucial to the physical properties of (K,Tl)(y)Fe(2-x)Se(2).

PMID- 21867082
TI  - Equilibration of Luttinger liquid and conductance of quantum wires.
AB  - Luttinger liquid theory describes one-dimensional electron systems in terms of
      noninteracting bosonic excitations. In this approximation thermal excitations are
      decoupled from the current flowing through a quantum wire, and the conductance is
      quantized. We show that relaxation processes not captured by the Luttinger liquid
      theory lead to equilibration of the excitations with the current and give rise to
      a temperature-dependent correction to the conductance. In long wires, the
      magnitude of the correction is expressed in terms of the velocities of bosonic
      excitations. In shorter wires it is controlled by the relaxation rate.

PMID- 21867083
TI  - Extremely correlated Fermi liquids.
AB  - We present the theory of an extremely correlated Fermi liquid with U->infinity.
      This liquid has an underlying auxiliary Fermi liquid Green's function that is
      further caparisoned by extreme correlations. The theory leads to two parallel
      hierarchies of equations that permit iterative approximations in a certain
      parameter. Preliminary results for the spectral functions display a broad
      background and a distinct T dependent left skew. An important energy scale
      Delta(k[over ->],x) emerges as the average inelasticity of the FL Green's
      function, and influences the photoemission spectra profoundly. A duality is
      identified wherein a loss of coherence of the ECFL results from an excessively
      sharp FL.

PMID- 21867084
TI  - Extremely correlated Fermi-liquid description of normal-state ARPES in cuprates.
AB  - The normal-state single particle spectral function of the high temperature
      superconducting cuprates, measured by the angle-resolved photoelectron
      spectroscopy (ARPES), has been considered both anomalous and crucial to
      understand. Here, we report an unprecedented success of the new extremely
      correlated Fermi liquid theory by one of us [B. S. Shastry, Phys. Rev. Lett. 107,
      056403 (2011)] to describe both laser and conventional synchrotron ARPES data
      (nodal cut at optimal doping) on Bi(2)Sr(2)CaCu(2)O(8+delta) and synchrotron data
      on La(1.85)Sr(0.15)CuO(4). It fits all data sets with the same physical parameter
      values, satisfies the particle sum rule and successfully addresses two widely
      discussed kink anomalies in the dispersion.

PMID- 21867085
TI  - Proximity induced enhancement of the Curie temperature in hybrid spin injection
      devices.
AB  - We investigate the increase of the Curie temperature T(C) in a lateral spin
      injection geometry where the ferromagnetic (Ga,Mn)As injector and detector
      contacts are capped by a thin iron film. Because of interlayer coupling between
      Fe and (Ga,Mn)As T(C) gets enhanced by nearly 100% for the thinnest (Ga,Mn)As
      films. The use of the proximity effect might pave the way for practical
      implementation of spintronic devices.

PMID- 21867086
TI  - Nonequilibrium Zeeman splitting in quantum transport through nanoscale junctions.
AB  - We calculate the differential conductance G(V) through a quantum dot in an
      applied magnetic field. We use a Keldysh conserving approximation for weakly
      correlated and the scattering-states numerical renormalization group for the
      intermediate and strongly correlated regime out of equilibrium. In the weakly
      correlated regime, the Zeeman splitting observable in G(V) strongly depends on
      the asymmetry of the device. In contrast, in the strongly correlated regime the
      position Delta(K) of the Zeeman-split zero-bias anomaly is almost independent of
      such asymmetries and of the order of the Zeeman energy Delta(0). We find a
      crossover from the purely spin-fluctuation driven Kondo regime at small magnetic
      fields with Delta(K)<Delta(0) to a regime at large fields where the contribution
      of charge fluctuations induces larger splittings with Delta(K)>Delta(0) as it was
      observed in recent experiments.

PMID- 21867087
TI  - Coexistence of superconductivity and ferromagnetism in two dimensions.
AB  - Ferromagnetism is usually considered to be incompatible with conventional
      superconductivity, as it destroys the singlet correlations responsible for the
      pairing interaction. Superconductivity and ferromagnetism are known to coexist in
      only a few bulk rare-earth materials. Here we report evidence for their
      coexistence in a two-dimensional system: the interface between two bulk
      insulators, LaAlO(3) (LAO) and SrTiO(3) (STO), a system that has been studied
      intensively recently. Magnetoresistance, Hall, and electric-field dependence
      measurements suggest that there are two distinct bands of charge carriers that
      contribute to the interface conductivity. The sensitivity of properties of the
      interface to an electric field makes this a fascinating system for the study of
      the interplay between superconductivity and magnetism.

PMID- 21867088
TI  - Surface scattering via bulk continuum states in the 3D topological insulator
      Bi2Se3.
AB  - We have performed scanning tunneling microscopy and differential tunneling
      conductance (dI/dV) mapping for the surface of the three-dimensional topological
      insulator Bi(2)Se(3). The fast Fourier transformation applied to the dI/dV image
      shows an electron interference pattern near Dirac node despite the general belief
      that the backscattering is well suppressed in the bulk energy gap region. The
      comparison of the present experimental result with theoretical surface and bulk
      band structures shows that the electron interference occurs through the
      scattering between the surface states near the Dirac node and the bulk continuum
      states.

PMID- 21867089
TI  - CO oxidation facilitated by robust surface states on Au-covered topological
      insulators.
AB  - Surface states--the electronic states emerging as a solid material terminates at
      a surface--are usually vulnerable to contaminations and defects. The robust
      topological surface state(s) (TSS) on the three-dimensional topological
      insulators provide a perfect platform for exploiting surface states in less
      stringent environments. Employing first-principles density functional theory
      calculations, we demonstrate that the TSS can play a vital role in facilitating
      surface reactions by serving as an effective electron bath. We use CO oxidation
      on gold-covered Bi(2)Se(3) as a prototype example, and show that the robust TSS
      can significantly enhance the adsorption energy of both CO and O(2) molecules, by
      promoting different directions of static electron transfer. The concept of TSS as
      an electron bath may lead to new design principles beyond the conventional d-band
      theory of heterogeneous catalysis.

PMID- 21867090
TI  - Pressure tuning of the interplay of magnetism and superconductivity in CeCu2Si2.
AB  - We carried out specific-heat and ac-susceptibility experiments under hydrostatic
      pressure to investigate the interplay of spin-density-wave antiferromagnetism (A)
      and superconductivity (S) in single-crystalline AS-type CeCu(2)Si(2). We find
      evidence for a line of magnetic-field- and pressure-tuned quantum critical points
      in the normal state in the zero-temperature magnetic field-pressure plane. Our
      analysis suggests an extension of this line into the superconducting state and
      corroborates the close connection of the underlying mechanisms leading to the
      formation of the antiferromagnetic and the superconducting states in AS-type
      CeCu(2)Si(2).

PMID- 21867091
TI  - Formation of multiple-flux-quantum vortices in mesoscopic superconductors from
      simulations of calorimetric, magnetic, and transport properties.
AB  - Because of strong flux confinement in mesoscopic superconductors, a "giant"
      vortex may appear in the ground state of the system in an applied magnetic field.
      This multiquanta vortex can then split into individual vortices (and vice versa)
      as a function of, e.g., applied current, magnetic field, or temperature. Here we
      show that such transitions can be identified by calorimetry, as the formation or
      splitting of a giant vortex results in a clear jump in measured heat capacity
      versus external drive. We attribute this phenomenon to an abrupt change in the
      density of states of the quasiparticle excitations in the vortex core(s), and
      further link it to a sharp change of the magnetic susceptibility at the
      transition--proving that the formation of a giant vortex can also be detected by
      magnetometry.

PMID- 21867092
TI  - Observation of electronic ferroelectric polarization in multiferroic YMn2O5.
AB  - We report the observation of a magnetic polarization of the O 2p states in
      YMn(2)O(5) through the use of soft x-ray resonant scattering at the oxygen K
      edge. Remarkably, we find that the temperature dependence of the integrated
      intensity of this signal closely follows the macroscopic electric polarization,
      and hence is proportional to the ferroelectric order parameter. This is in
      contrast with the temperature dependence observed at the Mn L(3) edge, which
      reflects the Mn magnetic order parameter. First-principles calculations provide a
      microscopic understanding of these results and show that a spin-dependent
      hybridization of O 2p and Mn 3d states results in a purely electronic
      contribution to the ferroelectric polarization, which can exist in the absence of
      lattice distortions.

PMID- 21867093
TI  - Interaction-induced partitioning and magnetization jumps in the mixed-spin oxide
      FeTiO3-Fe2O3.
AB  - In this study we report on jumps in the magnetic moment of the hemo-ilmenite
      solid solution (x)FeTiO(3)-(1-x)Fe(2)O(3) above Fe(III) percolation at low
      temperature (T<3 K). The first jumps appear at 2.5 K, one at each side of the
      magnetization loop, and their number increases with decreasing temperature and
      reaches 5 at T=0.5 K. The jumps occur after field reversal from a saturated state
      and are symmetrical in the trigger field and intensity with respect to the field
      axis. Moreover, an increase of the sample temperature by 2.8% at T=2.0 K
      indicates the energy released after the ignition of the magnetization jump, as
      the spin-currents generated by the event are dissipated in the lattice. The
      magnetization jumps are further investigated by Monte Carlo simulations, which
      show that these effects are a result of magnetic interaction-induced partitioning
      on a sublattice level.

PMID- 21867094
TI  - Metastability of free cobalt and iron clusters: a possible precursor to bulk
      ferromagnetism.
AB  - Homonuclear cobalt and iron clusters Co(N) and Fe(N) measured in a cryogenic
      molecular beam exist in two states with distinct magnetic moments (MU),
      polarizabilities, and ionization potentials, indicating distinct valences. The MU
      is approximately quantized: MU(N)~2NMU(B) in the ground states and
      MU(N)(*)~NMU(B) in the excited states for Co; MU(N)~3NMU(B) and MU(N)(*)~NMU(B)
      for Fe. At a large size, the average MU of the two states converges to the bulk
      value with diminishing ionization potential differences. The experiments suggest
      localized ferromagnetism in the two states and that itinerant ferromagnetism
      emerges from their superposition.

PMID- 21867095
TI  - Bistable coupling states measured on single Co nanoclusters deposited on
      CoO(111).
AB  - We describe novel features of the induced magnetic anisotropy in Co nanoclusters
      coupled with a CoO(111) layer. Individual cluster magnetism was studied using new
      microbridge superconducting quantum interference devices. Intrinsically, the Co
      clusters are single domains with an effective anisotropy constant K(F)~1.5*10(6)
      erg.cm(-3). A bistable state of the ferromagnetic-antiferromagnetic coupling is
      revealed, with a maximum bias systematically observed along CoO[10 1] and an
      interfacial coupling energy of 0.9 erg.cm(-2). The small bias observed in cluster
      assembly results from an averaging over the two opposite stable states.

PMID- 21867096
TI  - Optical stark effect and dressed exciton states in a Mn-doped CdTe quantum dot.
AB  - We report on the observation of spin-dependent optically dressed states and the
      optical Stark effect on an individual Mn spin in a semiconductor quantum dot. The
      vacuum-to-exciton or the exciton-to-biexciton transitions in a Mn-doped quantum
      dot are optically dressed by a strong laser field, and the resulting spectral
      signature is measured in photoluminescence. We demonstrate that the energy of any
      spin state of a Mn atom can be independently tuned by using the optical Stark
      effect induced by a control laser. High resolution spectroscopy reveals a power-,
      polarization-, and detuning-dependent Autler-Townes splitting of each optical
      transition of the Mn-doped quantum dot. This experiment demonstrates an optical
      resonant control of the exciton-Mn system.

PMID- 21867097
TI  - Ultrafast nonlinear optical response of a single gold nanorod near its surface
      plasmon resonance.
AB  - The ultrafast optical nonlinearity of an optically characterized single gold
      nanorod is investigated around its surface plasmon resonance, by combining a far
      field spatial modulation technique with a high sensitivity pump-probe setup. The
      spectrally and temporally dependent response is quantitatively interpreted in
      terms of the bulklike optical nonlinearity enhanced by the plasmonic effect. The
      plasmon resonance dynamics is shown to be mostly governed by nonequilibrium
      electron and phonon processes. Their contributions to the nonlinear optical
      response of a single metal nano-object are elucidated, and the latter is
      connected to the nonlinearities of ensembles.

PMID- 21867098
TI  - First-principles investigation of morphotropic transitions and phase-change
      functional responses in BiFeO3-BiCoO3 multiferroic solid solutions.
AB  - We present an ab initio study of the BFCO solid solution formed by multiferroics
      BiFeO(3) (BFO) and BiFeO(3) (BCO). We find that BFCO presents a strongly
      discontinuous morphotropic transition between BFO-like and BCO-like ferroelectric
      phases. Further, for all compositions such phases remain (meta)stable and retain
      well-differentiated properties. Our results thus suggest that an electric field
      can be used to switch between these structures and show that such a switching
      involves large phase-change effects of various types, including piezoelectric,
      electric, and magnetoelectric ones.

PMID- 21867099
TI  - Giant flexoelectric effect in ferroelectric epitaxial thin films.
AB  - We report on nanoscale strain gradients in ferroelectric HoMnO(3) epitaxial thin
      films, resulting in a giant flexoelectric effect. Using grazing-incidence in
      plane x-ray diffraction, we measured strain gradients in the films, which were 6
      or 7 orders of magnitude larger than typical values reported for bulk oxides. The
      combination of transmission electron microscopy, electrical measurements, and
      electrostatic calculations showed that flexoelectricity provides a means of
      tuning the physical properties of ferroelectric epitaxial thin films, such as
      domain configurations and hysteresis curves.

PMID- 21867100
TI  - Active colloidal suspensions exhibit polar order under gravity.
AB  - Recently, the steady sedimentation profile of a dilute suspension of chemically
      powered colloids was studied experimentally [J. Palacci et al., Phys. Rev. Lett.
      105, 088304 (2010)]. It was found that the sedimentation length increases
      quadratically with the swimming speed of the active Brownian particles. Here we
      investigate theoretically the sedimentation of self-propelled particles
      undergoing translational and rotational diffusion. We find that the measured
      increase of the sedimentation length is coupled to a partial alignment of the
      suspension with the mean swimming direction oriented against the gravitational
      field. We suggest realistic parameter values to observe this polar order.
      Furthermore, we find that the dynamics of the active suspension can be derived
      from a generalized free energy functional.

PMID- 21867101
TI  - Editorial: Redefining length.

PMID- 21867102
TI  - Scaling of cluster heterogeneity in percolation transitions.
AB  - We investigate a critical scaling law for the cluster heterogeneity H in site and
      bond percolations in d-dimensional lattices with d = 2,...,6. The cluster
      heterogeneity is defined as the number of distinct cluster sizes. As an
      occupation probability p increases, the cluster size distribution evolves from a
      monodisperse distribution to a polydisperse one in the subcritical phase, and
      back to a monodisperse one in the supercritical phase. We show analytically that
      H diverges algebraically, approaching the percolation critical point p(c) as H |p
      p(c)|(-1/sigma) with the critical exponent sigma associated with the
      characteristic cluster size. Interestingly, its finite-size-scaling behavior is
      governed by a new exponent nu H = 1+d (f)/(d)nu, where d(f) is the fractal
      dimension of the critical percolating cluster and nu is the correlation length
      exponent. The corresponding scaling variable defines a singular path to the
      critical point. All results are confirmed by numerical simulations.

PMID- 21867103
TI  - Nonuniversal behavior of the helicity modulus in a dense defect system.
AB  - An extensive Monte Carlo simulation has been performed on a two-dimensional
      modified XY model that behaves like a dense defect system. Topological defects
      are shown to introduce disorder in the system, which makes the helicity modulus
      jump nonuniversal. The results corroborate the experimental observation of a
      nonuniversal jump of the superconducting density in high-Tc superconducting
      films.

PMID- 21867104
TI  - Thermal Casimir drag in fluctuating classical fields.
AB  - A uniformly moving inclusion which locally suppresses the fluctuations of a
      classical thermally excited field is shown to experience a drag force that
      depends on the dynamics of the field. It is shown that in a number of cases the
      linear friction coefficient is dominated by short distance fluctuations and takes
      a very simple form. Examples where this drag can occur are for stiff objects,
      such as proteins, nonspecifically bound to more flexible ones such as polymers
      and membranes.

PMID- 21867105
TI  - Polarization periodicity in the B(1) columnar phase determined by resonant x-ray
      scattering.
AB  - We report structural results that evidence the polarization distribution of the
      blocks in the columnar phase of an achiral bent-core liquid crystal. The study
      was performed using resonant x-ray diffraction at the sulfur K edge on oriented
      samples aligned on substrates. The extra periodicity is revealed through the
      violation of the systematic extinction rule of the structural symmetry group
      along the experimentally accessible diffraction direction. Further data obtained
      from the polarization analysis of a resonant reflection give information
      concerning the transition mechanism between B(1) and B(2) phases.

PMID- 21867106
TI  - Molecular simulation of hierarchical structures in bent-core nematic liquid
      crystals.
AB  - The structure of nematic liquid crystals formed by bent-core mesogens (BCMs) is
      studied in the context of Monte Carlo simulations of a simple molecular model
      that captures the symmetry, shape, and flexibility of achiral BCMs. The results
      indicate the formation of (i) clusters exhibiting local smectic order, orthogonal
      or tilted, with strong in-layer polar correlations and antiferroelectric
      juxtaposition of successive layers and (ii) large homochiral domains through the
      helical arrangement of the tilted smectic clusters, while the orthogonal clusters
      produce achiral (untwisted) nematic states.

PMID- 21867107
TI  - Single-file diffusion of particles with long-range interactions: damping and
      finite-size effects.
AB  - We study the single file diffusion of a cyclic chain of particles that cannot
      cross each other, in a thermal bath, with long-ranged interactions and arbitrary
      damping. We present simulations that exhibit new behaviors specifically
      associated with systems of small numbers of particles and with small damping. In
      order to understand those results, we present an original analysis based on the
      decomposition of the particles' motion in the normal modes of the chain. Our
      model explains all dynamic regimes observed in our simulations and provides
      convincing estimates of the crossover times between those regimes.

PMID- 21867108
TI  - Complexity of several constraint-satisfaction problems using the heuristic
      classical algorithm WalkSAT.
AB  - We determine the complexity of several constraint-satisfaction problems using the
      heuristic algorithm WalkSAT. At large sizes N, the complexity increases
      exponentially with N in all cases. Perhaps surprisingly, out of all the models
      studied, the hardest for WalkSAT is the one for which there is a polynomial time
      algorithm.

PMID- 21867109
TI  - Crossover between structured and well-mixed networks in an evolutionary
      prisoner's dilemma game.
AB  - In a spatial evolutionary prisoner's dilemma game (PDG), individuals interact
      with their neighbors and update their strategies according to some rules. As is
      well known, cooperators are destined to become extinct in a well-mixed
      population, whereas they could emerge and be sustained on a structured network.
      In this work, we introduce a simple model to investigate the crossover between a
      structured network and a well-mixed one in an evolutionary PDG. In the model,
      each link j is designated a rewiring parameter tau(j), which defines the time
      interval between two successive rewiring events for link j. By adjusting the
      rewiring parameter tau (the mean time interval for any link in the network), we
      could change a structured network into a well-mixed one. For the link rewiring
      events, three situations are considered: one synchronous situation and two
      asynchronous situations. Simulation results show that there are three regimes of
      tau: large tau where the density of cooperators rho(c) rises to rho(c,infinity)
      (the value of rho(c) for the case without link rewiring), small tau where the
      mean-field description for a well-mixed network is applicable, and moderate tau
      where the crossover between a structured network and a well-mixed one happens.

PMID- 21867110
TI  - Fokker-Planck equation with arbitrary dc and ac fields: continued fraction
      method.
AB  - The continued fraction method (CFM) is used to solve the Fokker-Planck equation
      with arbitrary dc and ac fields. With an appropriate choice of basis functions,
      the Fokker-Planck equation is converted into a set of linear algebraic equations
      with short-ranged coupling and then CFM is implemented to obtain numerical
      solutions with high efficiency. Both a proposed perturbative CFM and the
      numerically exact matrix CFM are used to study the nonlinear response of driven
      systems, with their results compared to assess the validity regime of the
      perturbative approach. The proposed perturbative CFM approach needs scalar
      quantities only and hence is more efficient within its validity regime. Two
      nonlinear systems of different nature are used as examples: molecular dipole
      (rotational Brownian motion) and particle in a periodic potential (translational
      Brownian motion). The associated full dynamics is presented in the compact form
      of hysteresis loops. It is observed that as the strength of an AC driving field
      increases, pronounced nonlinear effects are manifested in the deformation of the
      hysteresis loops.

PMID- 21867111
TI  - Conserved noise restricted-solid-on-solid model on fractal substrates.
AB  - A conserved noise restricted solid-on-solid model on both a Sierpinski gasket
      substrate and a checkerboard fractal substrate is studied. The interface width W
      grows as t(beta) at early time t and becomes saturated at L(alpha) for t >> L(z),
      where L is the system size. We obtain beta ~ 0.0788, alpha ~ 0.377 for a
      Sierpinski gasket, and beta ~ 0.100, alpha ~ 0.516 for a checkerboard fractal.
      The dynamic exponent z ~ 4.79 for a Sierpinski gasket and z ~ 5.16 for a
      checkerboard fractal are obtained by the relation z = alpha/beta. They satisfy
      the scaling relations 4 alpha + 2 d(f) = z and z = 2 z(rw), where z(rw) is the
      random-walk exponent of the fractal substrate. A fractional Langevin equation is
      introduced to describe the model.

PMID- 21867112
TI  - Ground states of the lattice-gas model on the triangular lattice with nearest-
      and next-nearest-neighbor pairwise interactions and with three-particle
      interaction: full-dimensional ground states.
AB  - In this paper, we completely solve the problem of the ground states of the
      lattice-gas model on the infinite plane triangular lattice with nearest- and next
      nearest-neighbor pairwise interactions and with additional interaction between
      three particles at the vertices of a nearest-neighbor triangle. We use this model
      to illustrate how the complete solution of the ground-state problem of a lattice
      gas model (or equivalent spin model) should look.

PMID- 21867113
TI  - Temperature-resonant cyclotron spectra in confined geometries.
AB  - We consider a two-dimensional gas of colliding charged particles confined to
      finite size containers of various geometries and subjected to a uniform
      orthogonal magnetic field. The gas spectral densities are characterized by a
      broad peak at the cyclotron frequency. Unlike for infinitely extended gases,
      where the amplitude of the cyclotron peak grows linearly with temperature, here
      confinement causes such a peak to go through a maximum for an optimal
      temperature. In view of the fluctuation-dissipation theorem, the reported
      resonance effect has a direct counterpart in the electric susceptibility of the
      confined magnetized gas.

PMID- 21867114
TI  - Optimal vertex cover for the small-world Hanoi networks.
AB  - The vertex-cover problem on the Hanoi networks HN3 and HN5 is analyzed with an
      exact renormalization group and parallel-tempering Monte Carlo simulations. The
      grand canonical partition function of the equivalent hard-core repulsive lattice
      gas problem is recast first as an Ising-like canonical partition function, which
      allows for a closed set of renormalization-group equations. The flow of these
      equations is analyzed for the limit of infinite chemical potential, at which the
      vertex-cover problem is attained. The relevant fixed point and its neighborhood
      are analyzed and nontrivial results are obtained both for the coverage as well as
      for the ground-state entropy density, which indicates the complex structure of
      the solution space. Using special hierarchy-dependent operators in the
      renormalization group and Monte Carlo simulations, structural details of optimal
      configurations are revealed. These studies indicate that the optimal coverages
      (or packings) are not related by a simple symmetry. Using a clustering analysis
      of the solutions obtained in the Monte Carlo simulations, a complex solution
      space structure is revealed for each system size. Nevertheless, in the
      thermodynamic limit, the solution landscape is dominated by one huge set of very
      similar solutions.

PMID- 21867115
TI  - Geometric stochastic resonance in a double cavity.
AB  - Geometric stochastic resonance of particles diffusing across a porous membrane
      subject to oscillating forces is characterized as a synchronization process.
      Noninteracting particle currents through a symmetric membrane pore are driven
      either perpendicular or parallel to the membrane, whereas, harmonic-mixing
      spectral current components are generated by the combined action of perpendicular
      and parallel drives. In view of potential applications to the transport of
      colloids and biological molecules through narrow pores, we also consider the role
      of particle repulsion as a controlling factor.

PMID- 21867116
TI  - Information flow and information production in a population system.
AB  - An approach aiming to quantify the dynamics of information within a population is
      developed based on the mapping of the processes underlying the system's evolution
      into a birth and death type stochastic process and the derivation of a balance
      equation for the information entropy. Information entropy flux and information
      entropy production are identified and their time-dependent properties, as well as
      their dependence on the parameters present in the problem, are analyzed. States
      of minimum information entropy production are shown to exist for appropriate
      parameter values. Furthermore, uncertainty and information production are
      transiently intensified when the population traverses the inflexion point stage
      of the logisticlike growth process.

PMID- 21867117
TI  - Instantaneous gelation in Smoluchowski's coagulation equation revisited.
AB  - We study the solutions of the Smoluchowski coagulation equation with a
      regularization term which removes clusters from the system when their mass
      exceeds a specified cutoff size, M. We focus primarily on collision kernels which
      would exhibit an instantaneous gelation transition in the absence of any
      regularization. Numerical simulations demonstrate that for such kernels with
      monodisperse initial data, the regularized gelation time decreases as M
      increases, consistent with the expectation that the gelation time is zero in the
      unregularized system. This decrease appears to be a logarithmically slow function
      of M, indicating that instantaneously gelling kernels may still be justifiable as
      physical models despite the fact that they are highly singular in the absence of
      a cutoff. We also study the case when a source of monomers is introduced in the
      regularized system. In this case a stationary state is reached. We present a
      complete analytic description of this regularized stationary state for the model
      kernel, K(m(1),m(2)) = max{m(1),m(2)}(nu), which gels instantaneously when M ->
      infinity if nu>1. The stationary cluster size distribution decays as a stretched
      exponential for small cluster sizes and crosses over to a power law decay with
      exponent nu for large cluster sizes. The total particle density in the stationary
      state slowly vanishes as [(nu-1)log M](-1/2) when M -> infinity. The approach to
      the stationary state is nontrivial: Oscillations about the stationary state
      emerge from the interplay between the monomer injection and the cutoff, M, which
      decay very slowly when M is large. A quantitative analysis of these oscillations
      is provided for the addition model which describes the situation in which
      clusters can only grow by absorbing monomers.

PMID- 21867119
TI  - Thermodynamic model of nonequilibrium phase transitions.
AB  - Within the scope of a thermodynamic description using the maximum entropy
      production principle, transitions from one nonequilibrium (kinetic) regime to
      another are considered. It is shown that in the case when power-law dependencies
      of thermodynamic flux on force are similar for two regimes, only a transition
      accompanied by a positive jump of thermodynamic flux is possible between them. It
      is found that the difference in powers of the dependencies of thermodynamic
      fluxes on forces results in a number of interesting nonequilibrium transitions
      between kinetic regimes, including the reentrant one with a negative jump of
      thermodynamic flux.

PMID- 21867118
TI  - Fluctuation-driven Turing patterns.
AB  - Models of diffusion-driven pattern formation that rely on the Turing mechanism
      are utilized in many areas of science. However, many such models suffer from the
      defect of requiring fine tuning of parameters or an unrealistic separation of
      scales in the diffusivities of the constituents of the system in order to predict
      the formation of spatial patterns. In the context of a very generic model of
      ecological pattern formation, we show that the inclusion of intrinsic noise in
      Turing models leads to the formation of "quasipatterns" that form in generic
      regions of parameter space and are experimentally distinguishable from standard
      Turing patterns. The existence of quasipatterns removes the need for unphysical
      fine tuning or separation of scales in the application of Turing models to real
      systems.

PMID- 21867120
TI  - Entanglement evolution and quantum phase transition of biased s = 1/2 spin-boson
      model.
AB  - The ground state and the spectral structure of lower-lying excited states of a
      dissipative two-level system coupled to a sub-Ohmic bath (s = 1/2) with nonzero
      bias have been studied using the unitary transformation method. By calculating
      the ground-state entanglement entropy, the ground-state average of sigma(z)(G),
      and the static susceptibility of the two-level system, we explore the nature of
      the transition (crossover) between the delocalized and localized state of the two
      level system. Furthermore, we calculate the time-dependent expectation
      (sigma(z)(t)) and the time evolution of the entanglement entropy to show that,
      when the system undergoes a transition (crossover) from the delocalized to the
      localized state, the time evolution of the two-level system changes from coherent
      to decoherent dynamics.

PMID- 21867121
TI  - Entropy production in nonequilibrium steady states: a different approach and an
      exactly solvable canonical model.
AB  - We discuss entropy production in nonequilibrium steady states by focusing on
      paths obtained by sampling at regular (small) intervals, instead of sampling on
      each change of the system's state. This allows us to directly study entropy
      production in systems with microscopic irreversibility. The two sampling methods
      are equivalent otherwise, and the fluctuation theorem also holds for the
      different paths. We focus on a fully irreversible three-state loop, as a
      canonical model of microscopic irreversibility, finding its entropy distribution,
      rate of entropy production, and large deviation function in closed analytical
      form, and showing that the observed kink in the large deviation function arises
      solely from microscopic irreversibility.

PMID- 21867122
TI  - Heat-flow properties of systems with alternate masses or alternate on-site
      potentials.
AB  - We address a central issue of phononics: the search of properties or mechanisms
      to manage the heat flow in reliable materials. We analytically study standard and
      simple systems modeling the heat flow in solids, namely, the harmonic, self
      consistent harmonic and also anharmonic chains of oscillators, and we show an
      interesting insulating effect: While in the homogeneous models the heat flow
      decays as the inverse of the particle mass, in the chain with alternate masses it
      decays as the inverse of the square of the mass difference, that is, it decays
      essentially as the mass ratio (between the smaller and the larger one) for a
      large mass difference. A similar effect holds if we alternate on-site potentials
      instead of particle masses. The existence of such behavior in these different
      systems, including anharmonic models, indicates that it is a ubiquitous
      phenomenon with applications in the heat flow control.

PMID- 21867123
TI  - Classical van der Waals interactions between spherical bodies of dipolar fluid.
AB  - The van der Waals interaction free energy A(int) between two spherical bodies of
      Stockmayer fluid across a vacuum is calculated using molecular simulations and
      classical perturbation theory. The results are decomposed into their
      electrostatic and Lennard-Jones parts, and the former is shown to agree
      excellently with predictions from dielectric continuum theory. A(int) is
      decomposed into its energetic and entropic contributions and the results are
      compared with analytical predictions. Finally, we expand the electrostatic part
      of A(int) in a multipole expansion, and show that the surprisingly good agreement
      between the molecular and continuum descriptions is likely due to a cancellation
      of errors coming from the neglect of the discrete nature of the fluid within the
      dielectric description.

PMID- 21867124
TI  - Effective one-dimensional description of confined diffusion biased by a
      transverse gravitational force.
AB  - Diffusion of pointlike noninteracting particles in a two-dimensional channel of
      varying cross section is considered. The particles are biased by a constant force
      in the transverse direction. A recurrence mapping procedure is applied, which
      enables the derivation of an effective one-dimensional (1D) evolution equation
      that governs the 1D density of the particles in the channel. In the limit of
      stationary flow, an extended Fick-Jacobs equation is reached, which is corrected
      by an effective diffusion coefficient D(x) that depends on the longitudinal
      coordinate x. The result is an approximate formula for D(x) that also involves
      the influence of the transverse force. The calculations are verified by the
      stationary diffusion in a linear cone, which is exactly solvable.

PMID- 21867125
TI  - Height distribution of the Kardar-Parisi-Zhang equation with sharp-wedge initial
      condition: numerical evaluations.
AB  - The time-dependent probability distribution function of the height for the Kardar
      Parisi-Zhang equation with sharp wedge initial conditions has been obtained
      recently as a convolution between the Gumbel distribution and a difference of two
      Fredholm determinants. We evaluate numerically this distribution over the whole
      time span. The crossover from the short time behavior, which is Gaussian, to the
      long time behavior, which is governed by the Gaussian unitary ensemble (GUE)
      Tracy-Widom distribution, is clearly visible.

PMID- 21867126
TI  - Performance of pinning-controlled synchronization.
AB  - In this work we address the problem of controlling a complex network toward a
      synchronous evolution by using the pinning-control strategy. In considering this
      control approach, we investigate the effect of the number of pinned nodes and how
      the strategy performance behaves in accordance with the type of nodes that are
      chosen to be controlled. The roles of the control and coupling gains are also
      discussed.

PMID- 21867127
TI  - Dissipation in a finite-size bath.
AB  - We investigate the interaction of a particle with a finite-size bath represented
      by a set of independent linear oscillators with frequencies that fall within a
      finite bandwidth. We discover that when the oscillators have particular frequency
      distributions, the finite-size bath behaves much as an infinite-size bath
      exhibiting dissipation properties and thus allowing irreversible energy
      absorption from a particle immersed in it. We also present a reinterpretation of
      the Langevin equation using a perturbation approach in which the small parameter
      represents the inverse of the number of oscillators in the bath, elucidating the
      relationship between finite-size and infinite-size bath responses.

PMID- 21866993
TI  - Measurement of the W+ W- cross section in sqrt(s) = 7  TeV pp collisions with
      ATLAS.
AB  - This Letter presents a measurement of the W+ W- production cross section in
      sqrt(s) = 7  TeV pp collisions by the ATLAS experiment, using 34  pb(-1) of
      integrated luminosity produced by the Large Hadron Collider at CERN. Selecting
      events with two isolated leptons, each either an electron or a muon, 8 candidate
      events are observed with an expected background of 1.7 +/- 0.6 events. The
      measured cross section is 41(-16)(+20)(stat) +/- 5(syst)+/-1(lumi)  pb, which is
      consistent with the standard model prediction of 44 +/- 3  pb calculated at next
      to-leading order in QCD.

PMID- 21867128
TI  - Effect of Coulombic friction on spatial displacement statistics.
AB  - The phenomenon of Coulombic friction enters the stochastic description of dry
      friction between two solids and the statistic characterization of vibrating
      granular media. Here we analyze the corresponding Fokker-Planck equation
      including both velocity and spatial components, exhibiting a formal connection to
      a quantum mechanical harmonic oscillator in the presence of a delta potential.
      Numerical solutions for the resulting spatial displacement statistics show a
      crossover from exponential to Gaussian displacement statistics. We identify a
      transient intermediate regime that exhibits multiscaling properties arising from
      the contribution of Coulombic friction. The possible role of these effects during
      observations in diffusion experiments is briefly discussed.

PMID- 21867132
TI  - Relaxation to equilibrium of the expectation values in macroscopic quantum
      systems.
AB  - A quantum mechanical explanation of the relaxation to equilibrium is shown for
      macroscopic systems for nonintegrable cases and numerically verified. The
      macroscopic system is initially in an equilibrium state, subsequently externally
      perturbed during a finite time, and then isolated for a sufficiently long time.
      We show a quantitative explanation that the initial microcanonical state
      typically reaches a state whose expectation values are well approximated by the
      average over another microcanonical ensemble.

PMID- 21867130
TI  - Elastic Maier-Saupe-Zwanzig model and some properties of nematic elastomers.
AB  - We introduce a simple mean-field lattice model to describe the behavior of
      nematic elastomers. This model combines the Maier-Saupe-Zwanzig approach to
      liquid crystals and an extension to lattice systems of the Warner-Terentjev
      theory of elasticity, with the addition of quenched random fields. We use
      standard techniques of statistical mechanics to obtain analytic solutions for the
      full range of parameters. Among other results, we show the existence of a stress
      strain coexistence curve below a freezing temperature, analogous to the P-V
      diagram of a simple fluid, with the disorder strength playing the role of
      temperature. Below a critical value of disorder, the tie lines in this diagram
      resemble the experimental stress-strain plateau and may be interpreted as
      signatures of the characteristic polydomain-monodomain transition. Also, in the
      monodomain case, we show that random fields may soften the first-order transition
      between nematic and isotropic phases, provided the samples are formed in the
      nematic state.

PMID- 21867133
TI  - Microcanonical entropy inflection points: key to systematic understanding of
      transitions in finite systems.
AB  - We introduce a systematic classification method for the analogs of phase
      transitions in finite systems. This completely general analysis, which is
      applicable to any physical system and extends toward the thermodynamic limit, is
      based on the microcanonical entropy and its energetic derivative, the inverse
      caloric temperature. Inflection points of this quantity signal cooperative
      activity and thus serve as distinct indicators of transitions. We demonstrate the
      power of this method through application to the long-standing problem of liquid
      solid transitions in elastic, flexible homopolymers.

PMID- 21867129
TI  - Defect dynamics in crystalline buckled membranes.
AB  - We study the dynamics of defect annihilation in flexible crystalline membranes
      suffering a symmetry-breaking phase transition. The kinetic process leading the
      system toward equilibrium is described through a Brazovskii-Helfrich-Canham
      Hamiltonian. In membranes, a negative disclination has a larger energy than a
      positive disclination. Here we show that this energetic asymmetry does not only
      affect equilibrium properties, like the Kosterlitz-Thouless transition
      temperature, but also plays a fundamental role in the dynamic of defects. Both
      unbinding of dislocations and Carraro-Nelson "antiferromagnetic" interactions
      between disclinations slow down the dynamics below the Lifshitz-Safran regime
      observed in flat hexagonal systems.

PMID- 21867131
TI  - Contact process with sublattice symmetry breaking.
AB  - We study a contact process with creation at first- and second-neighbor sites and
      inhibition at first neighbors, in the form of an annihilation rate that increases
      with the number of occupied first neighbors. Mean-field theory predicts three
      phases: inactive (absorbing), active symmetric, and active asymmetric, the latter
      exhibiting distinct sublattice densities on a bipartite lattice. These phases are
      separated by continuous transitions; the phase diagram is re-entrant. Monte Carlo
      simulations in two dimensions verify these predictions qualitatively, except for
      a first-neighbor creation rate of zero. (In the latter case one of the phase
      transitions is discontinuous.) Our numerical results confirm that the symmetric
      asymmetric transition belongs to the Ising universality class, and that the
      active-absorbing transition belongs to the directed percolation class, as
      expected from symmetry considerations.

PMID- 21867135
TI  - Effective environments: preparation of stationary states with inverse temperature
      ranging from positive to negative values.
AB  - In this paper, we discuss how effective environments incorporating periodic
      measurements can be used to prepare a two-level system (TLS) in almost arbitrary
      thermal states: Concretely, we study a TLS coupled to a spin environment, the
      magnetization of which is measured periodically. In ensemble average these
      measurements cause a relaxation of the TLS into a thermal (diagonal) state. By
      adjusting the time between the measurements and the detuning of the environmental
      spins, the creation of very low temperatures as well as inversion becomes
      possible. Our analytical results derived for large environments are numerically
      shown to be valid even for quite small environments, down to only a few spins.

PMID- 21867134
TI  - Order in a multidimensional system.
AB  - We show that any convex K-dimensional system has a level of order R that is
      proportional to its level of Fisher information I. The proportionality constant
      is 1/8 the square of the longest chord connecting two surface points of the
      system. This result follows solely from the requirement that R decrease under
      small perturbations caused by a coarse graining of the system. The form for R is
      generally unitless, allowing the order for different phenomena, or different
      representations (e.g., using time vs frequency) of a given phenomenom, to be
      compared objectively. Order R is also invariant to uniform magnification of the
      system. The monotonic contraction properties of R and I define an arrow of time
      and imply that they are entropies, in addition to their usual status as
      informations. This also removes the need for data, and therefore an observer, in
      derivations of nonparticipatory phenomena that utilize I. Simple graphical
      examples of the new order measure show that it measures as well the level of
      "complexity" in the system. Finally, an application to cell growth during
      enforced distortion shows that a single hydrocarbon chain can be distorted into a
      membrane having equal order or complexity. Such membranes are prime constituents
      of living cells.

PMID- 21867137
TI  - Two-dimensional optical thermal ratchets based on Fibonacci spirals.
AB  - An ensemble of symmetric potential energy wells arranged at the vertices of a
      Fibonacci spiral can serve as the basis for an irreducibly two-dimensional
      thermal ratchet. Periodic rotation of the potential energy landscape through a
      three-step cycle drives trapped Brownian particles along spiral trajectories
      through the pattern. Which spiral is selected depends on the angular displacement
      at each step, with transitions between selected spirals arising at rational
      proportions of the golden angle. Fibonacci spiral ratchets therefore display an
      exceptionally rich range of transport properties, including inhomogeneous states
      in which different parts of the pattern induce motion in different directions.
      Both the radial and angular components of these trajectories can undergo flux
      reversal as a function of the scale of the pattern or the rate of rotation.

PMID- 21867136
TI  - Social consensus through the influence of committed minorities.
AB  - We show how the prevailing majority opinion in a population can be rapidly
      reversed by a small fraction p of randomly distributed committed agents who
      consistently proselytize the opposing opinion and are immune to influence.
      Specifically, we show that when the committed fraction grows beyond a critical
      value p(c) ~ 10%, there is a dramatic decrease in the time T(c) taken for the
      entire population to adopt the committed opinion. In particular, for complete
      graphs we show that when p < pc, T(c) ~ exp [alpha(p)N], whereas for p>p(c), T(c)
      ~ ln N. We conclude with simulation results for Erdos-Renyi random graphs and
      scale-free networks which show qualitatively similar behavior.

PMID- 21867138
TI  - Active motion assisted by correlated stochastic torques.
AB  - The stochastic dynamics of an active particle undergoing a constant speed and
      additionally driven by an overall fluctuating torque is investigated. The random
      torque forces are expressed by a stochastic differential equation for the angular
      dynamics of the particle determining the orientation of motion. In addition to a
      constant torque, the particle is supplemented by random torques, which are
      modeled as an Ornstein-Uhlenbeck process with given correlation time tau(c).
      These nonvanishing correlations cause a persistence of the particles'
      trajectories and a change of the effective spatial diffusion coefficient. We
      discuss the mean square displacement as a function of the correlation time and
      the noise intensity and detect a nonmonotonic dependence of the effective
      diffusion coefficient with respect to both correlation time and noise strength. A
      maximal diffusion behavior is obtained if the correlated angular noise
      straightens the curved trajectories, interrupted by small pirouettes, whereby the
      correlated noise amplifies a straightening of the curved trajectories caused by
      the constant torque.

PMID- 21867140
TI  - First-passage-time processes and subordinated Schramm-Loewner evolution.
AB  - We study the first-passage-time processes of the anomalous diffusion on the self
      similar curves in two dimensions. The scaling properties of the mean-square
      displacement and mean first passage time of the fractional Brownian motion and
      subordinated walk on the different fractal curves (loop-erased random walk,
      harmonic explorer, and percolation front) are derived. We also define natural
      parametrized subordinated Schramm-Loewner evolution (NS-SLE) as a mathematical
      tool that can model diffusion on fractal curves. The scaling properties of the
      mean-square displacement and mean first passage time for NS-SLE are obtained by
      numerical means.

PMID- 21867139
TI  - From computed microtomography images to resistivity index calculations of
      heterogeneous carbonates using a dual-porosity pore-network approach: influence
      of percolation on the electrical transport properties.
AB  - Standard reservoir evaluations are based on Archie's law relating the average
      water saturation to the average electrical resistivity by R(ind) = S(w)(-2).
      However, especially in the case of complex heterogeneous carbonates, deviation
      from Archie's law is observed and generally attributed to factors affecting the
      percolation or disconnectedness of the different phases (wetting films,
      microporosity, macropores) assuring electrical conductance. Pore-network models
      (PNM's) in combination with high-resolution computed microtomography (MU-CT)
      constitute a very effective tool to investigate the influence of the geometry and
      topology of the porous media on the spatial distribution of the conductive phase,
      and therefore on the shape of the resistivity index curve. An extended version of
      the classical PNM applicable to dual-porosity systems is presented. It combines
      the classical pore-network modeling applied on the macroporous space with the
      macroscopic properties of the microporous phase, supposing that the two pore
      systems act in parallel. Three-dimensional images provide information on the
      connectedness of the microporous phase, which is then included in the
      simulations. Electrical behavior of sandstone and two carbonates presenting
      distinct resistivity index curves were simulated and compared to measurements.
      Both Archie and "non-Archie" behavior were correctly reproduced, and the curve
      shape was explained considering percolation of the different phases.

PMID- 21867141
TI  - Optimal dimensionality reduction of complex dynamics: the chess game as diffusion
      on a free-energy landscape.
AB  - Dimensionality reduction is ubiquitous in the analysis of complex dynamics. The
      conventional dimensionality reduction techniques, however, focus on reproducing
      the underlying configuration space, rather than the dynamics itself. The
      constructed low-dimensional space does not provide a complete and accurate
      description of the dynamics. Here I describe how to perform dimensionality
      reduction while preserving the essential properties of the dynamics. The approach
      is illustrated by analyzing the chess game--the archetype of complex dynamics. A
      variable that provides complete and accurate description of chess dynamics is
      constructed. The winning probability is predicted by describing the game as a
      random walk on the free-energy landscape associated with the variable. The
      approach suggests a possible way of obtaining a simple yet accurate description
      of many important complex phenomena. The analysis of the chess game shows that
      the approach can quantitatively describe the dynamics of processes where human
      decision-making plays a central role, e.g., financial and social dynamics.

PMID- 21867142
TI  - Decay of currents for strong interactions.
AB  - The decay of current autocorrelation functions is investigated for quantum
      systems featuring strong interactions. Here the term "interaction" refers to that
      part of the Hamiltonian causing the (major) decay of the current. On the time
      scale before the (first) zero crossing of the current, its relaxation is shown to
      be well described by a suitable perturbation theory in the lowest orders of the
      interaction strength, particularly if interactions are strong. In this
      description the relaxation is found to be rather close to a Gaussian decay and
      the resulting diffusion coefficient approximately scales with the inverse
      interaction strength. These findings are confirmed by numerical results from
      exact diagonalization for several one-dimensional transport models including spin
      transport in the Heisenberg chain with respect to different spin quantum numbers,
      anisotropy, next-nearest-neighbor interaction, or alternating magnetic field;
      energy transport in the Ising chain with tilted magnetic field; and transport of
      excitations in a randomly coupled modular quantum system. The impact of these
      results for weak interactions is discussed.

PMID- 21867144
TI  - Nonequilibrium work statistics of an Aharonov-Bohm flux.
AB  - We investigate the statistics of work performed on a noninteracting electron gas
      confined in a ring as a threaded magnetic field is turned on. For an electron gas
      initially prepared in a grand canonical state it is demonstrated that the
      Jarzynski equality continues to hold in this case, with the free energy replaced
      by the grand potential. The work distribution displays a marked dependence on the
      temperature. While in the classical (high-temperature) regime, the work
      probability density function follows a Gaussian distribution and the free energy
      difference entering the Jarzynski equality is null, the free energy difference is
      finite in the quantum regime, and the work probability distribution function
      becomes multimodal. We point out the dependence of the work statistics on the
      number of electrons composing the system.

PMID- 21867143
TI  - Detection of weak signals through nonlinear relaxation times for a Brownian
      particle in an electromagnetic field.
AB  - The detection of weak signals through nonlinear relaxation times for a Brownian
      particle in an electromagnetic field is studied in the dynamical relaxation of
      the unstable state, characterized by a two-dimensional bistable potential. The
      detection process depends on a dimensionless quantity referred to as the receiver
      output, calculated as a function of the nonlinear relaxation time and being a
      characteristic time scale of our system. The latter characterizes the complete
      dynamical relaxation of the Brownian particle as it relaxes from the initial
      unstable state of the bistable potential to its corresponding steady state. The
      one-dimensional problem is also studied to complement the description.

PMID- 21867145
TI  - Quasistationary states in the self-gravitating sheet model.
AB  - We study quasistationary states (QSSs) resulting from violent relaxation in the
      one-dimensional self-gravitating "sheet model," revisiting in particular the
      question of the adequacy of the theory of Lynden-Bell (LB) to describe them. For
      "waterbag" initial conditions characterized by a single phase-space density, the
      prediction of this theory is, in this model, a function of only one parameter,
      which can conveniently be chosen to be the ratio of the energy to that in the
      degenerate limit. Studying a class of such initial conditions in which the shape
      of the initial waterbag is varied, we find that the LB predictions are reasonably
      good always in the low-energy region, while at higher energies (i.e., in the
      nondegenerate limit) they are generally not even qualitatively correct, although
      certain initial conditions can still be found where they are as good as at low
      energy. We find notably that, in line with what has been observed by Levin et al.
      in some other models, when LB theory does not work, the QSSs are always
      characterized by the presence of a degenerate core, which these authors explain
      as the result of dynamical resonances. In short, LB theory appears to be a good
      approximation only when violent relaxation is sufficiently "gentle," and
      otherwise a degenerate core-halo structure results.

PMID- 21867146
TI  - Hard rigid rods on a Bethe-like lattice.
AB  - We study a system of long rigid rods of fixed length k with only excluded volume
      interaction. We show that, contrary to the general expectation, the self
      consistent field equations of the Bethe approximation do not give the exact
      solution of the problem on the Bethe lattice in this case. We construct a new
      lattice, called the random locally treelike layered lattice, which allows a dense
      packing of rods, and we show that the Bethe self-consistent equations are exact
      for this lattice. For a four-coordinated lattice, k-mers with k >= 4 undergo a
      continuous isotropic-nematic phase transition. For even coordination number q >=
      6, the transition exists only for k >= k(min)(q), and is discontinuous.

PMID- 21867147
TI  - Large deviations of ergodic counting processes: a statistical mechanics approach.
AB  - The large-deviation method allows to characterize an ergodic counting process in
      terms of a thermodynamic frame where a free energy function determines the
      asymptotic nonstationary statistical properties of its fluctuations. Here we
      study this formalism through a statistical mechanics approach, that is, with an
      auxiliary counting process that maximizes an entropy function associated with the
      thermodynamic potential. We show that the realizations of this auxiliary process
      can be obtained after applying a conditional measurement scheme to the original
      ones, providing is this way an alternative measurement interpretation of the
      thermodynamic approach. General results are obtained for renewal counting
      processes, that is, those where the time intervals between consecutive events are
      independent and defined by a unique waiting time distribution. The underlying
      statistical mechanics is controlled by the same waiting time distribution,
      rescaled by an exponential decay measured by the free energy function. A scale
      invariance, shift closure, and intermittence phenomena are obtained and
      interpreted in this context. Similar conclusions apply for nonrenewal processes
      when the memory between successive events is induced by a stochastic waiting time
      distribution.

PMID- 21867148
TI  - Levy targeting and the principle of detailed balance.
AB  - We investigate confining mechanisms for Levy flights under premises of the
      principle of detailed balance. In this case, the master equation of the jump-type
      process admits a transformation to the Levy-Schrodinger semigroup dynamics akin
      to a mapping of the Fokker-Planck equation into the generalized diffusion
      equation. This sets a correspondence between above two stochastic dynamical
      systems, within which we address a (stochastic) targeting problem for an
      arbitrary stability index MU epsilon (0,2) of symmetric Levy drivers. Namely,
      given a probability density function, specify the semigroup potential, and thence
      the jump-type dynamics for which this PDF is actually a long-time asymptotic
      (target) solution of the master equation. Here, an asymptotic behavior of
      different MU-motion scenarios ceases to depend on MU. That is exemplified by
      considering Gaussian and Cauchy family target PDFs. A complementary problem of
      the reverse engineering is analyzed: given a priori a semigroup potential,
      quantify how sensitive upon the choice of the MU driver is an asymptotic behavior
      of solutions of the associated master equation and thus an invariant PDF itself.
      This task is accomplished for so-called MU family of Levy oscillators.

PMID- 21867149
TI  - Dynamic quantum tunneling in mesoscopic driven Duffing oscillators.
AB  - We investigate the dynamic quantum tunneling between two attractors of a
      mesoscopic driven Duffing oscillator. We find that, in addition to inducing a
      remarkable quantum shift of the bifurcation point, the mesoscopic nature also
      results in a perfect linear scaling behavior for the tunneling rate with the
      driving distance to the shifted bifurcation point.

PMID- 21867150
TI  - Responses to applied forces and the Jarzynski equality in classical oscillator
      systems coupled to finite baths: an exactly solvable nondissipative nonergodic
      model.
AB  - Responses of small open oscillator systems to applied external forces have been
      studied with the use of an exactly solvable classical Caldeira-Leggett model in
      which a harmonic oscillator (system) is coupled to finite N-body oscillators
      (bath) with an identical frequency (omega(n) = omega(o) for n = 1 to N). We have
      derived exact expressions for positions, momenta, and energy of the system in
      nonequilibrium states and for work performed by applied forces. A detailed study
      has been made on an analytical method for canonical averages of physical
      quantities over the initial equilibrium state, which is much superior to
      numerical averages commonly adopted in simulations of small systems. The
      calculated energy of the system which is strongly coupled to a finite bath is
      fluctuating but nondissipative. It has been shown that the Jarzynski equality is
      valid in nondissipative nonergodic open oscillator systems regardless of the rate
      of applied ramp force.

PMID- 21867151
TI  - Summing free unitary random matrices.
AB  - I use quaternion free probability calculus--an extension of free probability to
      non-Hermitian matrices (which is introduced in a succinct but self-contained way)
      -to derive in the large-size limit the mean densities of the eigenvalues and
      singular values of sums of independent unitary random matrices, weighted by
      complex numbers. In the case of circular unitary ensemble summands, I write them
      in terms of two "master equations," which I then solve and numerically test in
      four specific cases. I conjecture a finite-size extension of these results,
      exploiting the complementary error function. I prove a central limit theorem, and
      its first subleading correction, for independent identically distributed zero
      drift unitary random matrices.

PMID- 21867152
TI  - Velocity fluctuations of population fronts propagating into metastable states.
AB  - The position of propagating population fronts fluctuates because of the
      discreteness of the individuals and stochastic character of processes of birth,
      death, and migration. Here we consider a Markov model of a population front
      propagating into a metastable state, and focus on the weak noise limit. For
      typical, small fluctuations the front motion is diffusive, and we calculate the
      front diffusion coefficient. We also determine the probability distribution of
      rare, large fluctuations of the front position and, for a given average front
      velocity, find the most likely population density profile of the front.
      Implications of the theory for population extinction risk are briefly considered.

PMID- 21867063
TI  - Indications of suppression of excited Upsilon states in Pb-Pb collisions at
      ?(s(NN))=2.76 TeV.
AB  - A comparison of the relative yields of Upsilon resonances in the MU(+)MU(-) decay
      channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of
      2.76 TeV is performed with data collected with the CMS detector at the LHC. Using
      muons of transverse momentum above 4  GeV/c and pseudorapidity below 2.4, the
      double ratio of the Upsilon(2S) and Upsilon(3S) excited states to the Upsilon(1S)
      ground state in Pb-Pb and pp collisions, [Upsilon(2S+3S)/Upsilon(1S)](Pb
      Pb)/[Upsilon(2S+3S)/Upsilon(1S)](pp), is found to be 0.31(-0.15)(+0.19)(stat)+/
      0.03(syst). The probability to obtain the measured value, or lower, if the true
      double ratio is unity, is calculated to be less than 1%.

PMID- 21867153
TI  - Perturbative path-integral study of active- and passive-tracer diffusion in
      fluctuating fields.
AB  - We study the effective diffusion constant of a Brownian particle linearly coupled
      to a thermally fluctuating scalar field. We use a path-integral method to compute
      the effective diffusion coefficient perturbatively to lowest order in the
      coupling constant. This method can be applied to cases where the field is
      affected by the particle (an active tracer) and cases where the tracer is
      passive. Our results are applicable to a wide range of physical problems, from a
      protein diffusing in a membrane to the dispersion of a passive tracer in a random
      potential. In the case of passive diffusion in a scalar field, we show that the
      coupling to the field can, in some cases, speed up the diffusion corresponding to
      a form of stochastic resonance. Our results on passive diffusion are also
      confirmed via a perturbative calculation of the probability density function of
      the particle in a Fokker-Planck formulation of the problem. Numerical simulations
      on simplified systems corroborate our results.

PMID- 21867158
TI  - Movers and shakers: granular damping in microgravity.
AB  - The response of an oscillating granular damper to an initial perturbation is
      studied using experiments performed in microgravity and granular dynamics
      simulations. High-speed video and image processing techniques are used to extract
      experimental data. An inelastic hard sphere model is developed to perform
      simulations and the results are in excellent agreement with the experiments. In
      line with previous work, a linear decay of the amplitude is observed. Although
      this behavior is typical for a friction-damped oscillator, through simulation it
      is shown that this effect is still present even when friction forces are absent.
      A simple expression is developed which predicts the optimal damping conditions
      for a given amplitude and is independent of the oscillation frequency and
      particle inelasticities.

PMID- 21867157
TI  - Temperature distribution inside an evaporating two-dimensional droplet lying on
      curved or flat substrates.
AB  - The temperature field inside an evaporating two-dimensional droplet resting on
      curved or flat isothermal substrates is studied under various evaporation
      conditions. An analytical solution for the temperature is derived, which can be
      directly used in the cases of pinned and depinned contact lines as well as in
      stick-slip evaporation modes. It is found that the temperature drop at the free
      surface of a droplet on a convex, hydrophobic substrate is far greater than that
      for flat or concave substrates of the same hydrophobicity. The analytical
      solution for the temperature field allows the direct estimate of the local
      temperature gradient and, hence, of the local surface tension gradient that gives
      rise to Marangoni flow directed from the contact lines to the top of the droplet.

PMID- 21867156
TI  - Quantum heat transfer in harmonic chains with self-consistent reservoirs: exact
      numerical simulations.
AB  - We describe a numerical scheme for exactly simulating the heat current behavior
      in a quantum harmonic chain with self-consistent reservoirs. Numerically exact
      results are compared to classical simulations and to the quantum behavior under
      the linear-response approximation. In the classical limit or for small
      temperature biases our results coincide with previous calculations. At large bias
      and for low temperatures the quantum dynamics of the system fundamentally differs
      from the close-to-equilibrium behavior, revealing in particular the effect of
      thermal rectification for asymmetric chains. Since this effect is absent in the
      classical analog of our model, we conclude that in the quantum model studied here
      thermal rectification is a purely quantum phenomenon, rooted in the quantum
      statistics.

PMID- 21867154
TI  - Enhancement of entropic transport by intermediates.
AB  - Brownian particles confined in a two-dimensional enclosure that give rise to a
      bistable entropic potential are considered. With the introduction of an
      intermediate lobe, the mean first passage time from one lobe to another through
      the intermediate shows a turnover behavior with the variation of the stability of
      the entropic intermediate. The mean escape time shows a minimum for an optimal
      value of the barrier height of the intermediate state. A three-state model is
      proposed to explain the nonmonotonic behavior of the entropic transport.

PMID- 21867155
TI  - Non-Hermitian Euclidean random matrix theory.
AB  - We develop a theory for the eigenvalue density of arbitrary non-Hermitian
      Euclidean matrices. Closed equations for the resolvent and the eigenvector
      correlator are derived. The theory is applied to the random Green's matrix
      relevant to wave propagation in an ensemble of pointlike scattering centers. This
      opens a new perspective in the study of wave diffusion, Anderson localization,
      and random lasing.

PMID- 21867159
TI  - Packings of deformable spheres.
AB  - We present an experimental study of disordered packings of deformable spheres.
      Fluorescent hydrogel spheres immersed in water together with a tomography
      technique enabled the imaging of the three-dimensional arrangement. The
      mechanical behavior of single spheres subjected to compression is first examined.
      Then the properties of packings of a randomized collection of deformable spheres
      in a box with a moving lid are tested. The transition to a state where the
      packing withstands finite stresses before yielding is observed. Starting from
      random packed states, the power law dependence of the normal force versus packing
      fraction or strain at different velocities is quantified. Furthermore, a
      compression-decompression sequence at low velocities resulted in rearrangements
      of the spheres. At larger packing fractions, a saturation of the mean
      coordination number took place, indicating the deformation and faceting of the
      spheres.

PMID- 21867160
TI  - Jamming in granular polymers.
AB  - We examine the jamming transition in a two-dimensional granular polymer system
      using compressional simulations. The jamming density Phi(c) decreases with
      increasing length of the granular chain due to the formation of loop structures,
      in excellent agreement with recent experiments. The jamming density can be
      further reduced in mixtures of granular chains and granular rings, also as
      observed in experiment. We show that the nature of the jamming in granular
      polymer systems has pronounced differences from the jamming behavior observed for
      polydisperse two-dimensional disk systems at point J. This result provides
      further evidence that there is more than one type of jamming transition.

PMID- 21867161
TI  - Segregation in horizontal rotating cylinders using magnetic resonance imaging.
AB  - The dynamics of granular materials, particularly radial and axial segregation in
      horizontal rotating cylinders containing large and small particles, is studied by
      Magnetic Resonance Imaging (MRI). Stationary three-dimensional (3D) images and
      real-time two-dimensional (2D) structural images showing radial segregation, band
      formation, and band merging are reported. Quantitative local particle
      concentrations are measured in a noninvasive manner from the different magnetic
      resonance responses of the seeds throughout segregation. Data are acquired with
      sufficiently high temporal (300 ms for 2D images) and spatial resolutions (0.94
      mm cubic voxels), to give insights into the underlying mechanisms of both radial
      and axial segregation. In particular, the increasing rate of the local particle
      concentration during radial segregation is quantified. Particle migration is
      observed in the bulk material of the 75% and 82% full cylinders during both
      radial and axial segregation, showing that this region beneath the avalanche
      layer does not behave as a solid body. We also provide direct experimental
      evidence to support recent numerical simulations of band merging.

PMID- 21867162
TI  - Tuning jammed frictionless disk packings from isostatic to hyperstatic.
AB  - We perform extensive computational studies of two-dimensional static bidisperse
      disk packings using two distinct packing-generation protocols. The first involves
      thermally quenching equilibrated liquid configurations to zero temperature over a
      range of thermal quench rates r and initial packing fractions followed by
      compression and decompression in small steps to reach packing fractions phi(J) at
      jamming onset. For the second, we seed the system with initial configurations
      that promote micro- and macrophase-separated packings followed by compression and
      decompression to phi(J). Using these protocols, we generate more than 10(4)
      static packings over a wide range of packing fraction, contact number, and
      compositional and positional order. We find that disordered, isostatic packings
      exist over a finite range of packing fractions in the large-system limit. In
      agreement with previous calculations, the most dilute mechanically stable
      packings with phi min ~ 0.84 are obtained for r > r*, where r* is the rate above
      which phi(J) is insensitive to rate. We further compare the structural and
      mechanical properties of isostatic versus hyperstatic packings. The structural
      characterizations include the contact number, several order parameters, and
      mixing ratios of the large and small particles. We find that the isostatic
      packings are positionally and compositionally disordered (with only small changes
      in a number of order parameters), whereas bond-orientational and compositional
      order increase strongly with contact number for hyperstatic packings. In
      addition, we calculate the static shear modulus and normal mode frequencies (in
      the harmonic approximation) of the static packings to understand the extent to
      which the mechanical properties of disordered, isostatic packings differ from
      partially ordered packings. We find that the mechanical properties of the
      packings change continuously as the contact number increases from isostatic to
      hyperstatic.

PMID- 21867163
TI  - Identification of rolling resistance as a shape parameter in sheared granular
      media.
AB  - Using contact dynamics simulations, we compare the effect of rolling resistance
      at the contacts in granular systems composed of disks with the effect of
      angularity in granular systems composed of regular polygonal particles. In simple
      shear conditions, we consider four aspects of the mechanical behavior of these
      systems in the steady state: shear strength, solid fraction, force and fabric
      anisotropies, and probability distribution of contact forces. Our main finding is
      that, based on the energy dissipation associated with relative rotation between
      two particles in contact, the effect of rolling resistance can explicitly be
      identified with that of the number of sides in a regular polygonal particle. This
      finding supports the use of rolling resistance as a shape parameter accounting
      for particle angularity and shows unambiguously that one of the main influencing
      factors behind the mechanical behavior of granular systems composed of
      noncircular particles is the partial hindrance of rotations as a result of
      angular particle shape.

PMID- 21867164
TI  - Granular flow during hopper discharge.
AB  - Granular material freely discharging from a hopper under gravity is one of the
      oldest and most widely studied problems in granular flow. Despite the apparent
      simplicity of the system, expressions relating the discharge rate of the hopper
      to the properties of the individual grains are difficult to determine and
      typically empirical in nature. A mathematical model for discharge from a hopper
      is derived based on the dynamics of individual particles just within the outlet.
      In contrast to previous models, this analysis derives a flow rate from granular
      dynamics, rather than dimensional arguments. The model, therefore, uses no
      assumptions about the form of the stress distribution within the hopper, or the
      addition of empirical factors or fitting parameters. Our model gives a flow rate
      identical in form to a well-known empirical expression, showing that an
      experimentally determined constant used in this expression is purely geometry
      dependent. Our analysis is also extended to derive an expression for the flow
      rate incorporating gas drag, which becomes dominant at small grain sizes,
      significantly reducing the outflow rate. The resulting expression shows excellent
      agreement with a range of computational simulations using a coupled discrete
      element and Navier-Stokes method. These simulations also show that the gas flow
      is much more complex than previously assumed in this region, and simplified
      assumptions used in prior hopper flow models do not hold.

PMID- 21867165
TI  - Time-dependent phase behavior of 5CB-DDAB-water microemulsions monitored by means
      of dielectric spectroscopy.
AB  - The phase behavior of an inverse microemulsion composed of 4-cyano-4-n
      pentylbiphenyl (5CB), didodecyl dimethyl ammonium bromide, and water was
      intensively studied recently, but controversy still remains on the existence of a
      "transparent nematic" (TN) phase. Previously, we studied the temperature
      dependent dielectric behavior of this microemulsion [Z. Chen and R. Nozaki, J.
      Chem. Phys. 134, 034505 (2011)]. The results suggested that a superstructure
      composed of water droplets and confined 5CB molecules exists in the coexistence
      phase region, which may correspond to the notion of a TN phase. In this study,
      the time-dependent dielectric behaviors of this microemulsion in the isotropic,
      coexistence, and supercooled phase regions were investigated. In the coexistence
      and supercooled phase regions, the dielectric behaviors showed strong dependence
      on time, due to the hysteresis of phase transition and the upward diffusion of
      the water-droplet-rich isotropic phase. After the isotropic phase has been
      totally excluded out of the effective measurement area, the slow process was
      still observed in these two phase regions, which suggests that water droplets can
      stably exist in the liquid crystalline phase. A local microscopic phase evolution
      was observed in the coexistence phase region, which is similar to the temperature
      induced phase evolution previously proposed by us. The dielectric behavior of the
      slow process during the phase evolution also suggests the existence of the
      superstructure. In addition, the mechanism of the slow process in different phase
      regions proposed in our previous study is also confirmed.

PMID- 21867166
TI  - Simulation of a two-dimensional model for colloids in a uniaxial electric field.
AB  - We perform Monte Carlo simulations of a simplified two-dimensional model for
      colloidal hard spheres in an external uniaxial ac electric field. Experimentally,
      the external field induces dipole moments in the colloidal particles, which in
      turn form chains. We therefore approximate the system as composed of well-formed
      chains of dipolar hard spheres of a uniform length. The dipolar interaction
      between colloidal spheres gives rise to an effective interaction between the
      chains, which we treat as disks in a plane, that includes a short-range
      attraction and long-range repulsion. Hence, the system favors finite clustering
      over bulk phase separation, and indeed we observe at low temperature and density
      that the system does form a cluster phase. As the density increases, percolation
      is accompanied by a pressure anomaly. The percolated phase, despite being
      composed of connected, locally crystalline domains, does not bear the typical
      signatures of a hexatic phase. At very low densities, we find no indication of a
      "void phase" with a cellular structure seen recently in experiments.

PMID- 21867167
TI  - Transport of superparamagnetic beads through a two-dimensional potential energy
      landscape.
AB  - The nonlinear dynamic behavior of superparamagnetic beads transported through a
      two-dimensional potential energy landscape is explored empirically and through
      numerical simulation. The beads are driven through a periodic array of
      micromagnets by an external rotating field oriented at an angle theta relative to
      the magnetization direction of the substrate. The bead's motion was highly
      sensitive to the angle of the driving field near critical angles and to various
      system parameters, including bead size, rotation frequency, and substrate pole
      density. Our results suggest the possibility of using this behavior in a highly
      discriminative colloidal separation system, in which two different bead types can
      be tuned to move in orthogonal directions.

PMID- 21867168
TI  - Foam invasion through a single pore.
AB  - We investigate experimentally the behavior of liquid foams pumped at a given flow
      rate through a single pore, in the situation where the pore diameter is smaller
      than the bubble diameter. Results reveal that foam invasion can be observed only
      within a restricted range of values for the dimensionless flow rate and the foam
      liquid fraction. Within this foam invasion regime, the liquid content of invading
      foams is measured to be three times higher than the initial liquid content.
      Outside this regime, both gas alone and liquid alone invasion regimes can be
      observed. The gas invasion regime results from the rupture of foam films during
      local T1, during bubble rearrangements events induced by foam flow, whereas the
      liquid invasion regime is allowed by the formation of a stable cluster of jammed
      bubbles at the pore's opening.

PMID- 21867169
TI  - Dynamics of shear-induced yielding and flow in dilute colloidal gels.
AB  - The transient microstructural response of dilute, depletion-induced colloidal
      gels to shear deformation is probed using a custom-built cone-and-plate shear
      cell mounted on a fast scanning confocal microscope. We directly unveil an
      important mode of nonlinear gel yielding, which marks the transition from an
      immobilized gel network to disconnected flowing clusters at large values of the
      accumulated strain (gamma ~ 0.7). The transition is mediated by a cascade of
      local rupture events that initiate at the sample's outer edges and propagate
      inward, resulting in transient dynamic and microstructural heterogeneities in the
      gel network. Based on the findings, we propose solvent-induced drag as the
      primary cause of nonlinear rupture, and discuss the coupling between the
      microstructural evolution and transient rheology in this system.

PMID- 21867170
TI  - Bulk modulus of poly(N-isopropylacrylamide) microgels through the swelling
      transition.
AB  - We report measurements of the bulk modulus of individual poly(N
      isopropylacrylamide) microgels along their swelling transition. The modulus is
      determined by measuring the volume deformation of the microgel as a function of
      osmotic pressure using dextran solutions. We find that the modulus softens
      through the transition, displaying a nonmonotonous behavior with temperature.
      This feature is correctly reproduced by the theory of Flory for polymer gels,
      once the concentration dependence of the solvency parameter is properly
      incorporated.

PMID- 21867171
TI  - Interaction regimes for oppositely charged plates with multivalent counterions.
AB  - Within a mean-field treatment of the interaction between two oppositely charged
      plates in a salt-free solution, the distance at which a transition from an
      attractive to a repulsive regime appears can be computed analytically. The mean
      field description, however, breaks down under strong Coulombic couplings, which
      can be achieved at room temperature with multivalent counterions and highly
      charged surfaces. Making use of the contact theorem and simple physical
      arguments, we propose explicit expressions for the equation of state in several
      situations at short distances. The possibility of Bjerrum pair formation is
      addressed and is shown to have profound consequences on the interactions. To
      complete the picture, we consider the large-distance limit, from which schematic
      phase diagram discriminating attractive from repulsive regions can be proposed.

PMID- 21867172
TI  - Robustness of avalanche dynamics in sheared amorphous solids as probed by
      transverse diffusion.
AB  - Using numerical simulations, we perform an extensive finite-size analysis of the
      transverse diffusion coefficient in a sheared 2D amorphous solid over a broad
      range of strain rates at temperatures up to the supercooled liquid regime. We
      thus obtain direct qualitative evidence for the persistence of correlations
      between elementary plastic events up to the vicinity of the glass transition
      temperature T(g). A quantitative analysis of the data, combined with a previous
      study of the T and gamma dependence of the macroscopic stress [Phys. Rev. Lett.
      105, 266001 (2010)], leads us to conclude that the average avalanche size remains
      essentially unaffected by temperature up to T ~ 0.75T(g).

PMID- 21867173
TI  - Dressed counterions: polyvalent and monovalent ions at charged dielectric
      interfaces.
AB  - We investigate the ion distribution and overcharging at charged interfaces with
      dielectric inhomogeneities in the presence of asymmetric electrolytes containing
      polyvalent and monovalent ions. We formulate an effective "dressed counterion"
      approach by integrating out the monovalent salt degrees of freedom and show that
      it agrees with results of explicit Monte Carlo simulations. We then apply the
      dressed counterion approach within the framework of the generalized strong
      coupling theory, valid for polyvalent ions at low concentrations, which enables
      an analytical description for salt effects as well as dielectric inhomogeneities
      in the limit of strong Coulomb interactions. Limitations and applicability of
      this theory are examined by comparing the results with simulations.

PMID- 21867174
TI  - Model of the cooperative rearranging region for polyhydric alcohols.
AB  - A simplified model of a hydrogen-bonding network is proposed in order to clarify
      the microscopic structure of the cooperative rearranging region (CRR) in Adam
      Gibbs theory [G. Adam and J. H. Gibbs, J. Chem. Phys. 43, 139 (1965)]. Our model
      can be solved analytically, and it successfully explains the reported systematic
      features of the glass transition of polyhydric alcohols. In this model, hydrogen
      bonding is formulated based on binding free energy. Assuming a cluster of
      molecules connected by double hydrogen bonds is a CRR and approximating the
      hydrogen-bonding network as a Bethe lattice in percolation theory, the
      temperature dependence of the structural relaxation time can be obtained
      analytically. Reported data on relaxation times are well described by the
      obtained equation. By taking the lower limit of the binding free energy with this
      equation, the Vogel-Fulcher-Tammann equation can be derived. Consequently, the
      fragility index and glass transition temperature can be expressed as functions of
      the number of OH groups in a molecule, and this relation agrees well with the
      reported experimental data.

PMID- 21867175
TI  - Simulation study on the trembling shear behavior of eletrorheological fluid.
AB  - The trembling shear behavior of electrorheological (ER) fluids has been
      investigated by using a computer simulation method, and a shear-slide boundary
      model is proposed to understand this phenomenon. A thiourea-doped Ba-Ti-O ER
      fluid which shows a trembling shear behavior was first prepared and then
      systematically studied by both theoretical and experimental methods. The shear
      curves of ER fluids in the dynamic state were simulated with shear rates from 0.1
      to 1000 s(-1) under different electric fields. The simulation results of the flow
      curves match the experimental results very well. The trembling shear curves are
      divided into four regions and each region can be explained by the proposed model.

PMID- 21867176
TI  - Glassy dynamics and hysteresis in a linear system of orientable hard rods.
AB  - We study the dynamics of a one-dimensional fluid of orientable hard rectangles
      with a non-coarse-grained microscopic mechanism of facilitation. The length
      occupied by a rectangle depends on its orientation, which is a discrete variable
      coupled to an external field. The equilibrium properties of our model are
      essentially those of the Tonks gas, but at high densities the orientational
      degrees of freedom become effectively frozen due to jamming. This is a simple
      analytically tractable model of the glassy phase. Under a cyclic variation of the
      pressure, hysteresis is observed. Following a pressure quench, the orientational
      persistence exhibits a two-stage decay characteristic of glassy systems.

PMID- 21867177
TI  - Dynamical heterogeneity in a highly supercooled liquid: consistent calculations
      of correlation length, intensity, and lifetime.
AB  - We have investigated dynamical heterogeneity in a highly supercooled liquid using
      molecular-dynamics simulations in three dimensions. Dynamical heterogeneity can
      be characterized by three quantities: correlation length xi(4), intensity chi(4),
      and lifetime tau(hetero). We evaluated all three quantities consistently from a
      single order parameter. In a previous study [H. Mizuno and R. Yamamoto, Phys.
      Rev. E 82, 030501(R) (2010)], we examined the lifetime tau(hetero)(t) in two time
      intervals t = tau(alpha) and tau(ngp), where tau(alpha) is the alpha-relaxation
      time and tau(ngp) is the time at which the non-Gaussian parameter of the Van Hove
      self-correlation function is maximized. In the present study, in addition to the
      lifetime tau(hetero)(t), we evaluated the correlation length xi(4)(t) and the
      intensity chi({4)(t) from the same order parameter used for the lifetime
      tau(hetero)(t). We found that as the temperature decreases, the lifetime
      tau(hetero)(t) grows dramatically, whereas the correlation length xi(4)(t) and
      the intensity chi(4)(t) increase slowly compared to tau(hetero)(t) or plateaus.
      Furthermore, we investigated the lifetime tau(hetero)(t) in more detail. We
      examined the time-interval dependence of the lifetime tau(hetero)(t) and found
      that as the time interval t increases, tau(hetero)(t) monotonically becomes
      longer and plateaus at the relaxation time of the two-point density correlation
      function. At the large time intervals for which tau(hetero)(t) plateaus, the
      heterogeneous dynamics migrate in space with a diffusion mechanism, such as the
      particle density.

PMID- 21867178
TI  - Spacing distribution functions for the one-dimensional point-island model with
      irreversible attachment.
AB  - We study the configurational structure of the point-island model for epitaxial
      growth in one dimension. In particular, we calculate the island gap and capture
      zone distributions. Our model is based on an approximate description of
      nucleation inside the gaps. Nucleation is described by the joint probability
      density p(n)(XY)(x,y), which represents the probability density to have
      nucleation at position x within a gap of size y. Our proposed functional form for
      p(n)(XY)(x,y) describes excellently the statistical behavior of the system. We
      compare our analytical model with extensive numerical simulations. Our model
      retains the most relevant physical properties of the system.

PMID- 21867179
TI  - Wetting and prewetting of water on top of a single sheet of hexagonal boron
      nitride.
AB  - Wetting of a single hexagonal boron nitride sheet by liquid water has been
      investigated by molecular dynamics simulations within a temperature range between
      278 and 373 K. The wetting temperature was found to be ~310 K, while the onset of
      prewetting happens around the much higher temperature of 354 K. The static
      (hydrogen-bond populations, density profiles, energy per molecule) and dynamic
      (diffusion coefficients) properties of water in the stable phases in this
      temperature range were also studied and compared to those of water on graphene.
      The results indicate that hydrophobicity of boron nitride is milder than that of
      graphene.

PMID- 21867180
TI  - Structural and evaporative evolutions in desiccating sessile drops of blood.
AB  - We report an experimental investigation of the drying of a deposited drop of
      whole blood. Flow motion, adhesion, gelation, and fracturation all occur during
      the evaporation of this complex matter, leading to a final typical pattern. Two
      distinct regimes of evaporation are highlighted: the first is driven by
      convection, diffusion, and gelation in a liquid phase, whereas the second, with a
      much slower rate of evaporation, is characterized by the mass transport of the
      liquid left over in the gellified biocomponent matter. A diffusion model of the
      drying process allows a prediction of the transition between these two regimes of
      evaporation. Moreover, the formation of cracks and other events occurring during
      the drying are examined and shown to be driven by critical solid mass
      concentrations.

PMID- 21867181
TI  - Effect of polymer on the elasticity of surfactant membranes: a light scattering
      study.
AB  - We have performed a dynamic light-scattering (DLS) investigation of the effect of
      a water-soluble polymer, polyethylene glycol (PEG), on the bending elastic
      modulus kappa of surfactant membranes. The polymer, in concentrations ranging
      from 0 to 8 g/L (0 to 0.4 mM), was incorporated into the solvent of sponge phases
      of the sodium dodecyl sulfate (SDS)-hexanol-brine system. PEG adsorbs into the
      SDS membranes. The correlation functions of the polymer-doped sponge phases
      displayed a stretched-exponential decay, appropriately described by the Zilman
      Granek (Z-G) theory for fluctuating membranes. The dynamics of the surfactant
      bilayers was slowed down by the addition of the polymer: Increasing PEG
      concentrations increase the DLS relaxation times. From the Z-G model we extracted
      the membrane-bending elastic modulus, as a function of polymer concentration,
      C(PEG) = kappa increases with C(PEG), a behavior opposite to that expected from
      available models for the interaction between fluid membranes and adsorbing
      polymers. Our results suggest that the polymer penetrates to some extent the
      surfactant bilayers.

PMID- 21867182
TI  - Localized buckling of a floating elastica.
AB  - We study the buckling of a two-dimensional elastica floating on a bath of dense
      fluid, subjected to axial compression. The sinusoidal pattern predicted by the
      analysis of linear stability is shown to become localized above the buckling
      threshold. A nonlinear amplitude equation is derived for the envelope of the
      pattern. These results provide a simple interpretation to the wrinkle-to-fold
      transition reported by Pocivavsek et al. [Science 320, 912 (2008)]. An analogy
      with the classical problem of the localized buckling of a strut on a nonlinear
      elastic foundation is presented.

PMID- 21867183
TI  - Single crystal growth and anisotropic crystal-fluid interfacial free energy in
      soft colloidal systems.
AB  - We measure the anisotropy of the crystal-fluid interfacial free energy in soft
      colloidal systems. A temperature gradient is used to direct crystal nucleation
      and control the growth of large single crystals in order to achieve well
      equilibrated crystal-fluid interfaces. Confocal microscopy is used to follow both
      the growth process and the equilibrium crystal-fluid interface at the particle
      scale: heterogeneous crystal nucleation, the advancing interface, and the
      stationary equilibrium interface. We use the measured growth velocity to
      determine the chemical potential difference between crystal and fluid phases.
      Well-equilibrated, large crystal-fluid interfaces are then used to determine the
      interfacial free energy and its anisotropy directly from thermally excited
      interface fluctuations. We find that while the measured average interfacial free
      energy is in good agreement with values found in simulations, the anisotropy is
      significantly larger than simulation values. Finally, we investigate the effect
      of impurities on the advancing interface. We determine the critical force needed
      to overcome impurity particles from the local interface curvature.

PMID- 21867184
TI  - Coarsening and accelerated equilibration in mass-conserving heterogeneous
      nucleation.
AB  - We propose a model of mass-conserving heterogeneous nucleation to describe the
      dynamics of ligand-receptor binding in closed cellular compartments. When the
      ligand dissociation rate is small, competition among receptors for free ligands
      gives rise to two very different long-time ligand-receptor cluster-size
      distributions. Cluster sizes first plateau to a long-lived, initial-condition
      dependent, "metastable" distribution, and coarsen only much later to a
      qualitatively different equilibrium one. Surprisingly, we also find parameters
      for which a very special subset of clusters have equal metastable and equilibrium
      sizes, appearing to equilibrate much faster than the rest. Our results provide a
      quantitative framework for ligand-binding kinetics and suggest a mechanism by
      which different clusters can approach their equilibrium sizes in unexpected ways.

PMID- 21867185
TI  - Internal degrees of freedom and transport of benzene on graphite.
AB  - In this paper, the chaotic internal degrees of freedom of a benzene molecule
      adsorbed on a graphite substrate, their interplay with thermal noise, and their
      effects on the diffusion and drift are investigated analytically by making use of
      the presence of two different time scales as well as by molecular-dynamics
      simulations. The effects of thermal noise are investigated, and it is found that
      noise does not significantly alter the dynamics of the internal degrees of
      freedom yet does affect the friction and diffusion of the center of mass.
      Qualitative and quantitative theoretical predictions for the friction and
      diffusion of the molecule on the substrate are made and are compared to molecular
      dynamics simulations. Contributions to the friction and diffusion from the finite
      heat bath as well as the slow dynamics of the center of mass are formally
      identified. It is shown that the torsion in benzene, which dominates the
      nonlinear coupling, significantly affects the friction of the molecule on the
      surface. The results compare favorably with recent results from He-neutron spin
      echo experiments on this system. Based on the analytical and numerical results,
      some suggestions are made for experimental conditions under which the effects of
      internal degrees of freedom might be observable.

PMID- 21867186
TI  - Nucleation, growth, and coarsening of crystalline domains in order-order
      transitions between lamellar and hexagonal phases.
AB  - Using the numerical solution of the time-dependent Ginzburg-Landau equation, we
      study the entire process of transformation between the lamellar and the hexagonal
      phases from the early-stage nucleation and growth to the late-stage coarsening
      regime. The metastable crystalline structure that nucleates first is identified
      in terms of the mean-field theory under the single-wave-number approximation.
      This has been borne out by the numerically efficient preparation of single
      crystal structure developed via the noise-induced self-organization. We also
      present results for the scaling of the late-time domain growth, which is
      quantified by two measures: the structure factor and the orientational
      correlation function. In particular, the growth exponent is shown to be robust
      and indifferent to conservation of the order parameter.

PMID- 21867187
TI  - Multimer formation for two-dimensional random nanoparticle deposition.
AB  - Efforts are currently under way to produce nanoparticle samples with a size
      dispersion as low as possible, using deposition of preformed clusters on a
      substrate. However, even for diluted cluster films, contact or coalescence
      between neighboring clusters cannot be totally avoided due to the random nature
      of the deposition process. Consequently, the incident particle-size distribution
      will necessarily be degraded, with the statistical formation of multimers
      (dimers, trimers, or more generally nmers). In this article, we consider diluted
      assemblies of nanoparticles (with a narrow size distribution) randomly deposited
      on a surface and develop theoretical tools to assess the various multimer
      proportions. We establish simple and reliable analytical approximations of the
      probability for a cluster to form an nmer and the subsequent multimer proportion.
      These results can be applied in the analysis of experimental samples: They
      constitute a convenient tool for experimentalists in the design of their
      nanoparticle sample and the interpretation of experimental measurements.

PMID- 21867188
TI  - Relaxation of surface steps after thermal quenches: a numerical study within the
      terrace-step-kink model.
AB  - We study the out-of-equilibrium relaxation of surface steps after thermal
      quenches using numerical simulations of the terrace-step-kink model for a vicinal
      surface. We analyze both single and interacting steps in a situation where the
      temperature is suddenly changed at a given quench time. We focus on a physically
      relevant range of temperatures and show that the relaxation of the roughness is
      compatible with a power-law behavior with an effective relaxation exponent close
      to gamma = 1/2 in all cases. This value is consistent with a one-dimensional
      Edwards-Wilkinson equation. In particular, this means that, although the case of
      interacting steps is effectively a two-dimensional system, its relaxation is
      dominated by short length-scale fluctuations, where steps are not interacting.

PMID- 21867189
TI  - Phase-field investigation of rod eutectic morphologies under geometrical
      confinement.
AB  - Three-dimensional phase-field simulations are employed to investigate rod-type
      eutectic growth morphologies in confined geometry. Distinct steady-state
      solutions are found to depend on this confinement effect with the rod array basis
      vectors and their included angle (alpha) changing to accommodate the geometrical
      constraint. Specific morphologies are observed, including rods of circular cross
      sections, rods of distorted (elliptical) cross sections, rods of peanut-shaped
      cross-sections, and lamellar structures. The results show that, for a fixed value
      of alpha > 10 degrees , the usual (triangular) arrays of circular rods are stable
      in a broad range of spacings, with a transition to the peanut-shaped cross
      sectioned rods occurring at large spacings (above 1.5 times the minimum
      undercooling spacing lambda(m)), and the advent of rod eliminations at low
      spacings. Furthermore, a transition from rod to lamellar structures is observed
      for alpha < 10 degrees  for the phase fraction of 10.5% used in the present
      paper.

PMID- 21867190
TI  - Boundary-layer method for the analytical calculation of stable textures of bent
      core liquid crystal fibers.
AB  - We study the equilibrium textures of molecular orientation inside cylindrical
      fibers made of coaxial layers of bent-core smectics. We propose a free-energy
      model taking into account surface-like and bulk contributions--including layer
      compression and electrostatic terms among others--with constant values of the
      material parameters. We follow the usual variational procedure of minimization of
      the free energy with respect to the tilt-angle profile theta(r) and obtain an
      Euler-Lagrange equation and its boundary condition. We solve the variational
      equations for the equilibrium configurations using a boundary-layer approximation
      and find multiple solutions. Since the equilibrium tilt profiles are found to be
      radially inhomogeneous, we select those with minimum distortions in order to find
      the lowest free-energy state. We minimize further the free energy of the system
      with respect to the fiber radius and find wider intervals of stability than those
      previously reported, depending on the balance of the material's spontaneous
      polarization, elastic and electric divergence-of-polarization constants, and
      surface-tension coefficients. The bulk and surface-layer structures thus found
      could be used to calculate the allowed modes of propagation of electromagnetic
      waves inside the fiber.

PMID- 21867191
TI  - Thermodynamic stability of the cubatic phase of hard cut spheres evaluated by
      expanded ensemble simulations.
AB  - The system of hard cut spheres (disk-shaped particles formed by symmetrically
      truncating the end caps of a sphere) exhibits an intriguing "cubatic" phase with
      cubic orientational symmetry. However, it is unclear whether this phase is
      metastable with respect to the columnar phase. We attempt to provide an answer to
      this question by carrying out free energy calculations by the expanded ensemble
      Monte Carlo method. We conclude that there may be a very small region of cubatic
      stability in the vicinity of the isotropic-cubatic phase transition, but that
      that transition would need to be determined more accurately to obtain a
      definitive answer. We also comment on the efficacy of the expanded ensemble
      method for these kinds of calculations.

PMID- 21867192
TI  - Orientationally ordered phase produced by fully antinematic interactions: a
      simulation study.
AB  - We consider here a classical model, consisting of D(2h) symmetric particles,
      whose centers of mass are associated with a three-dimensional simple-cubic
      lattice; the pair potential is isotropic in orientation space, and restricted to
      nearest neighbors. Two orthonormal triads define orientations of a pair of
      interacting particles; the simplest potential models proposed in the literature
      can be written as a linear combination involving the squares of the scalar
      products between corresponding unit vectors only, thus depending on three
      parameters, and making the interaction model rather versatile. A coupling
      constant with negative sign tends to keep the two interacting unit vectors
      parallel to each other, whereas a positive sign tends to keep them mutually
      orthogonal (antinematic coupling). We address here a special, extreme case of the
      above family, involving only antinematic couplings: more precisely, three
      antinematic terms whose coefficients are set to a common positive value (hence
      the name PPP model). The model under investigation produces a doubly degenerate
      pair ground state; the nearest-neighbor range of the interaction and the
      bipartite character of the lattice can propagate the pair ground state and
      increase the overall degeneracy, but without producing frustration. The model was
      investigated by a simplified molecular field treatment as well as by Monte Carlo
      simulation, whose results suggested a second-order transition to a low
      temperature biaxially ordered phase; ground-state configurations producing
      orientational order have been selected by thermal fluctuations. The molecular
      field treatment also predicted a continuous transition, and was found to
      overestimate the transition temperature by a factor 2.

PMID- 21867193
TI  - Molecular field theory for biaxial nematic liquid crystals composed of molecules
      with C(2h) point group symmetry.
AB  - The biaxial nematic phase is generally taken, either explicitly or implicitly, to
      have D(2h) point group symmetry. However, it is possible for the biaxial phase to
      have a lower symmetry depending on that of its constituent molecules. Here we
      develop a molecular field theory for a nematogen composed of C(2h) molecules in
      terms of the nine independent second rank orientational order parameters defining
      the C(2h) biaxial nematic. In addition, there is a rank one order parameter
      constructed from two pseudovectors which is only nonzero in the C(2h) phase. The
      theory is simplified by removing all but the three dominant order parameters. The
      predicted phase behavior is found to be rich with three possible biaxial nematic
      phases and with the transitions involving a biaxial nematic phase exhibiting
      tricritical points.

PMID- 21867194
TI  - Director alignment by crossed electric and magnetic fields: a deuterium NMR
      study.
AB  - The static director distribution in thin nematic liquid crystal cells, subject to
      both electric and magnetic fields, has been investigated using a combination of
      deuterium nuclear magnetic resonance (NMR) spectroscopy and continuum theory in
      terms of the director distribution function, which gives the probability density
      for finding the director at a given orientation. A series of deuterium NMR
      spectra for the nematic liquid crystal, 4-pentyl-d(2)-4'-cyanobiphenyl
      deuteriated in the alpha position of the pentyl chain were acquired as a function
      of the applied electric field. This powerful experimental technique allowed us to
      observe uniform and nonuniform director alignment depending on the angle between
      the two fields and their relative strength. On the basis of the detailed
      experimental results, we have explored the factors that influence the nature of
      both the uniform and the nonuniform director distributions. We have discussed the
      questions that are raised by our attempt to understand the static director
      distribution as a function of the angle between the two fields. We have
      discovered that the alignment of the director at the surface of the Teflon
      spacers is essential in addition to the random variation in the cell thickness in
      order to account for the static director distribution determined from the NMR
      spectra.

PMID- 21867195
TI  - Characterization of a chiral phase in an achiral bent-core liquid crystal by
      polarization studies of resonant x-ray forbidden reflections.
AB  - The chiral antiferroelectric structure of an achiral bent-core liquid crystal is
      characterized by resonant x-ray scattering at chlorine K edge. The "forbidden"
      reflections resulting from the glide or screw symmetry elements are restored by
      the anisotropy of the tensor structure factor, which we calculate for two
      possible structural models. A careful analysis of the polarization states of the
      restored "forbidden" reflections enables an unambiguous identification of a
      chiral structure (i.e., the so-called anticlinic, antiferroelectric smectic-C or
      Sm-C(A)P(A)) coexisting with the achiral synclinic antiferroelectric smectic-C or
      Sm-C(S)P(A). The method proves to be quite powerful as it identifies the chiral
      structure within coexisting phases despite an imperfect orientation of the
      sample. The volume fraction of the chiral phase and the distribution of alignment
      are extracted from the data.

PMID- 21867196
TI  - Theory of elastic interaction of colloidal particles in nematic liquid crystals
      near one wall and in the nematic cell.
AB  - We apply the method developed [Chernyshuk and Lev, Phys. Rev. E 81, 041701
      (2010)] for theoretical investigation of colloidal elastic interactions between
      axially symmetric particles in the confined nematic liquid crystal near one wall
      and in the nematic cell with thickness L. Both cases of homeotropic and planar
      director orientations are considered. Particularly, dipole-dipole, dipole
      quadrupole, and quadrupole-quadrupole interactions of the one particle with the
      wall and within the nematic cell are found as well as corresponding two particle
      elastic interactions. A set of results has been predicted: The effective power of
      repulsion between two dipole particles at height h near the homeotropic wall is
      reduced gradually from inverse 3 to 5 with an increase of dimensionless distance
      r / h; near the planar wall, the effect of dipole-dipole isotropic attraction is
      predicted for large distances r > r(dd) = 4.76 h; maps of attraction and
      repulsion zones are crucially changed for all interactions near the planar wall
      and in the planar cell; and one dipole particle in the homeotropic nematic cell
      was found to be shifted by the distance delta(eq) from the center of the cell.
      The proposed theory fits very well with experimental data for the confinement
      effect of elastic interaction between spheres in the homeotropic cell [Vilfan et
      al., Phys. Rev. Lett. 101, 237801 (2008)] in the range 1-1000 kT. The influence
      of the K(24) and K(13) terms as well as connection with other theoretical
      approaches are discussed.

PMID- 21867197
TI  - Biaxial smectic-A* phase and its possible misidentification as a smectic-Calpha*
      phase.
AB  - The biaxial smectic-A* (Sm-A(B)*) phase, appearing in the phase sequence Sm-A*-Sm
      A(B)*-Sm-C*, is analyzed using Landau theory. It is found to possess a helical
      superstructure with a pitch that is significantly shorter than the pitch of the
      Sm-C* helical superstructure. The Sm-A(B)*-Sm-C* transition can be either first
      or second order, and correspondingly there will be either a jump or continuous
      variation in the pitch. The behaviors of the birefringence and electroclinic
      effect are analyzed and found to be similar to those of a Sm-C(alpha)* phase. As
      such, it is possible that the Sm-A(B)* phase could be misidentified as a Sm
      C(alpha)* phase. Ways to distinguish the two phases are discussed.

PMID- 21867198
TI  - Quantitative definition of patterns in soft-mode turbulence suppressing the Nambu
      Goldstone mode.
AB  - Chaotic patterns in electroconvection of homeotropic nematics, soft-mode
      turbulence (SMT), and the related spatiotemporal chaos (STC) are discussed, and
      the quantitative definition of the patterns is considered. The order parameter S,
      obtained directly from the 2D spectra of the patterns, is introduced. The
      contribution of the Nambu-Goldstone mode and the increase in pattern regularity
      under the influence of an external magnetic field H are evaluated. We propose a
      schematic phase diagram of STC patterns based on the value of S.

PMID- 21867199
TI  - Relaxation dynamics of a polymer network modeled by a multihierarchical
      structure.
AB  - We numerically analyze the scaling behavior of experimentally accessible
      dynamical relaxation forms for polymer networks modeled by a finite
      multihierarchical structure. In the framework of generalized Gaussian structures,
      by making use of the eigenvalue spectrum of the connectivity matrix, we determine
      the averaged monomer displacement under local external forces as well as the
      mechanical relaxation quantities (storage and loss moduli). Hence we generalize
      the known analysis for both classes of fractals to the case of multihierarchical
      structure, for which even though we have a mixed growth algorithm, the above
      cited observables still give information about the two different underlying
      topologies. For very large lattices, reached via an algebraic procedure that
      avoids the numerical diagonalizations of the corresponding connectivity matrices,
      we depict the scaling of both component fractals in the intermediate time
      (frequency) domain, which manifests two different slopes.

PMID- 21867200
TI  - Domain patterns in a diblock copolymer-diblock copolymer mixture with oscillatory
      particles.
AB  - We investigate the orientational order transition of striped patterns in
      microphase structures of diblock copolymer-diblock copolymer mixtures in the
      presence of periodic oscillatory particles. Under certain conditions, although
      the macrophase separation of a system is almost isotropic, microphase separation
      of one diblock copolymer takes place and becomes anisotropic gradually. By
      changing the oscillatory frequency and amplitude, the orientational order
      transition of a striped microphase structure from the state parallel to the
      oscillatory direction to the state perpendicular to the oscillatory direction is
      observed. We also find that the order transition occurs when we change the
      initial composition ratio. Furthermore, we examine the domain size and the
      orientational order parameter of microstructure in the process of orientational
      order transition. The results may provide guidance for experimentalists. This
      model system can also give a simple way to realize orientational order transition
      of soft materials by changing the oscillatory field.

PMID- 21867201
TI  - Induced crystallization of single-chain polyethylene on a graphite surface:
      molecular dynamics simulation.
AB  - Molecular dynamics (MD) simulations have been carried out on the crystallization
      of single-chain polyethylene (PE) which was adsorbed on a graphite (001) surface
      on one side and exposed to vacuum on the other at different temperatures. The MD
      simulation data have been analyzed to provide information about the
      crystallization process of polymer adsorbed on the solid substrate. The
      isothermal crystallization of PE proceeds in two steps: (1) adsorption and (2)
      orientation. The results detail the radial density distribution function, ordered
      parameters, local bond-orientational order parameters, and the local properties
      displayed in layers of the polymer parallel to the graphite and vacuum
      interfaces. It was also shown that the film thickness affected the critical
      crystallization temperature of the adsorbed polymer on the substrate surface.
      Furthermore, the influence of the graphite surface area on the crystallization of
      PE is discussed by comparing the crystallinity evolution of PE on graphite with
      different coverage.

PMID- 21867202
TI  - Ideal linear-chain polymers with fixed angular momentum.
AB  - The statistical mechanics of a linear noninteracting polymer chain with a large
      number of monomers is considered with fixed angular momentum. The radius of
      gyration for a linear polymer is derived exactly by functional integration. This
      result is then compared to simulations done with a large number of noninteracting
      rigid links at fixed angular momentum. The simulation agrees with the theory up
      to finite-size corrections. The simulations are also used to investigate the
      anisotropic nature of a spinning polymer. We find universal scaling of the
      polymer size along the direction of the angular momentum, as a function of
      rescaled angular momentum.

PMID- 21867203
TI  - Characterization of polymer structures based on Burnside's lemma.
AB  - Polymer structure modeling is a trend of recent material sciences. Developments
      of computational science and nanotechnology make it possible to predict
      properties of complicated molecular structures. Many theoretical and
      computational methods have succeeded in elucidating the nature of polymer
      structures. It is not always best to model whole complicated structures depending
      on computer capabilities. Significant properties of materials may be manifested
      in simple structural aspects. In the present study, characteristics of a polymer
      structure are investigated by applying Burnside's lemma to the modeling
      procedure. This method is expected to be available to model polymers or molecular
      crystals in which functional groups play an important role in expressing their
      functions. Every structure under the symmetry and periodicity is counted
      completely and the energy distribution caused by the conformations of functional
      groups can be clarified. The detailed procedure is introduced and the present
      method is applied to a problem for investigating molecular structures of
      sulfonated poly(ether ether ketone) (SPEEK). SPEEK is focused on a candidate for
      proton exchange membranes in polymer electrolyte fuel cells. Sulfonic groups have
      a significant role in proton exchange membranes to make proton conduction
      channels. From our analysis, it is found that sulfonic groups tend to be
      dispersed in SPEEK membranes at their stable conditions. These are unfavorable
      characteristics for proton exchange membranes due to their difficulty to form
      desirable water channels inevitable for the high proton conductivity. This is one
      reason why SPEEK membranes are inferior to Nafion(r) membranes that express the
      highest performance as proton exchange membranes. Using the present method,
      experimental and theoretical results previously reported are confirmed and
      detailed characteristics are discussed in terms of structural simplicities.

PMID- 21867204
TI  - Intraglobular structures in multiblock copolymer chains from a Monte Carlo
      simulation.
AB  - Multiblock copolymer chains in implicit nonselective solvents are studied by
      using a Monte Carlo method, which employs a parallel tempering algorithm. Chains
      consisting of 120 A and 120 B monomers, arranged in three distinct
      microarchitectures: (10-10)12, (6-6)20, and (3-3)40, collapse to globular states
      upon cooling, as expected. By varying both the reduced temperature T* and the
      compatibility between monomers omega, numerous intraglobular structures are
      obtained: diclusters (handshake, spiral, torus with a core, etc.), triclusters,
      and n clusters with n>3 (lamellar and other), which are reminiscent of the block
      copolymer nanophases for spherically confined geometries. Phase diagrams for
      various chains in the (T*,omega) space are mapped. The structure factor S(k), for
      a selected microarchitecture and omega, is calculated. Since S(k) can be measured
      in scattering experiments, it can be used to relate simulation results to an
      experiment. Self-assembly in those systems is interpreted in terms of competition
      between minimization of the interfacial area separating different types of
      monomers and minimization of contacts between chain and solvent. Finally, the
      relevance of this model to the protein folding is addressed.

PMID- 21867205
TI  - Polymer segmental cross correlations from dielectric relaxation spectra of block
      copolymers.
AB  - Dielectric relaxation spectra of solutions of block polymers containing
      sequential type-A dipoles are considered from a theoretical correlation-function
      standpoint. Spectra of a specific set of block copolymers can be combined to
      isolate the dynamic cross-correlation between the motions of two distinct parts
      of the same polymer chain. Unlike past treatments of this problem, no model is
      assumed for the underlying polymer dynamics.

PMID- 21867206
TI  - Field-theoretical approach to a dense polymer with an ideal binary mixture of
      clustering centers.
AB  - We propose a field-theoretical approach to a polymer system immersed in an ideal
      mixture of clustering centers. The system contains several species of these
      clustering centers with different functionality, each of which connects a fixed
      number segments of the chain to each other. The field theory is solved using the
      saddle point approximation and evaluated for dense polymer melts using the random
      phase approximation. We find a short-ranged effective intersegment interaction
      with strength dependent on the average segment density and discuss the structure
      factor within this approximation. We also determine the fractions of linkers of
      the different functionalities.

PMID- 21867207
TI  - Dengue epidemics and human mobility.
AB  - In this work we explore the effects of human mobility on the dispersion of a
      vector borne disease. We combine an already presented stochastic model for dengue
      with a simple representation of the daily motion of humans on a schematic city of
      20 * 20 blocks with 100 inhabitants in each block. The pattern of motion of the
      individuals is described in terms of complex networks in which links connect
      different blocks and the link length distribution is in accordance with recent
      findings on human mobility. It is shown that human mobility can turn out to be
      the main driving force of the disease dispersal.

PMID- 21867208
TI  - Symmetry breaking of vesicle shapes in Poiseuille flow.
AB  - Vesicle behavior under unbounded axial Poiseuille flow is studied analytically.
      Our study reveals subtle features of the dynamics. It is established that there
      exists a stable off-centerline steady-state solution for low enough flow
      strength. This solution appears as a symmetry-breaking bifurcation upon lowering
      the flow strength and includes slipper shapes, which are characteristic of red
      blood cells in the microvasculature. A stable axisymmetric solution exists for
      any flow strength provided the excess area is small enough. It is shown that the
      mechanism of the symmetry breaking depends on the geometry of the flow: The
      bifurcation is subcritical in axial Poiseuille flow and supercritical in planar
      flow.

PMID- 21867209
TI  - Diffuse interface model of multicomponent vesicle adhesion and fusion.
AB  - Prefusion and postfusion states of the biological fusion process between lipid
      bilayer vesicle membranes are studied in this paper. Based on the Helfrich-type
      continuum theory, a diffuse interface model is developed which describes the
      phase changes on the deformable vesicles via a scalar phase field function, and
      incorporates the adhesion effect between the different phases of the vesicles
      through a nonlocal interaction potential. Various equilibrium configurations in
      the prefusion and postfusion states are examined. The effects of spontaneous
      curvatures, bending, and Gaussian rigidities on the fusion process are discussed.
      Instead of considering only the regions in close contact as in many previous
      studies, the present approach allows us to include the energetic contributions
      from all parts of the vesicles. By carrying out simulations based on the gradient
      flow of the associated energy functional, we are also able to elucidate the
      dynamic transitions between the prefusion and postfusion states.

PMID- 21867210
TI  - Network algorithmics and the emergence of information integration in cortical
      models.
AB  - An information-theoretic framework known as integrated information theory (IIT)
      has been introduced recently for the study of the emergence of consciousness in
      the brain [D. Balduzzi and G. Tononi, PLoS Comput. Biol. 4, e1000091 (2008)]. IIT
      purports that this phenomenon is to be equated with the generation of information
      by the brain surpassing the information that the brain's constituents already
      generate independently of one another. IIT is not fully plausible in its modeling
      assumptions nor is it testable due to severe combinatorial growth embedded in its
      key definitions. Here we introduce an alternative to IIT which, while inspired in
      similar information-theoretic principles, seeks to address some of IIT's
      shortcomings to some extent. Our alternative framework uses the same network
      algorithmic cortical model we introduced earlier [A. Nathan and V. C. Barbosa,
      Phys. Rev. E 81, 021916 (2010)] and, to allow for somewhat improved testability
      relative to IIT, adopts the well-known notions of information gain and total
      correlation applied to a set of variables representing the reachability of
      neurons by messages in the model's dynamics. We argue that these two quantities
      relate to each other in such a way that can be used to quantify the system's
      efficiency in generating information beyond that which does not depend on
      integration. We give computational results on our cortical model and on variants
      thereof that are either structurally random in the sense of an Erdos-Renyi random
      directed graph or structurally deterministic. We have found that our cortical
      model stands out with respect to the others in the sense that many of its
      instances are capable of integrating information more efficiently than most of
      those others' instances.

PMID- 21867211
TI  - Reducing blood viscosity with magnetic fields.
AB  - Blood viscosity is a major factor in heart disease. When blood viscosity
      increases, it damages blood vessels and increases the risk of heart attacks.
      Currently, the only method of treatment is to take drugs such as aspirin, which
      has, however, several unwanted side effects. Here we report our finding that
      blood viscosity can be reduced with magnetic fields of 1 T or above in the blood
      flow direction. One magnetic field pulse of 1.3 T lasting ~1 min can reduce the
      blood viscosity by 20%-30%. After the exposure, in the absence of magnetic field,
      the blood viscosity slowly moves up, but takes a couple of hours to return to the
      original value. The process is repeatable. Reapplying the magnetic field reduces
      the blood viscosity again. By selecting the magnetic field strength and duration,
      we can keep the blood viscosity within the normal range. In addition, such
      viscosity reduction does not affect the red blood cells' normal function. This
      technology has much potential for physical therapy.

PMID- 21867212
TI  - Motion of an elastic capsule in a square microfluidic channel.
AB  - In the present study we investigate computationally the steady-state motion of an
      elastic capsule along the centerline of a square microfluidic channel and compare
      it with that in a cylindrical tube. In particular, we consider a slightly over
      inflated elastic capsule made of a strain-hardening membrane with comparable
      shearing and area-dilatation resistance. Under the conditions studied in this
      paper (i.e., small, moderate, and large capsules at low and moderate flow rates),
      the capsule motion in a square channel is similar to and thus governed by the
      same scaling laws with the capsule motion in a cylindrical tube, even though in
      the channel the cross section in the upstream portion of large capsules is
      nonaxisymmetric (i.e., square-like with rounded corners). When the hydrodynamic
      forces on the membrane increase, the capsule develops a pointed downstream edge
      and a flattened rear (possibly with a negative curvature) so that the restoring
      tension forces are increased as also happens with droplets. Membrane tensions
      increase significantly with the capsule size while the area near the downstream
      tip is the most probable to rupture when a capsule flows in a microchannel.
      Because the membrane tensions increase with the interfacial deformation, a
      suitable Landau-Levich-Derjaguin-Bretherton analysis reveals that the lubrication
      film thickness h for large capsules depends on both the capillary number Ca and
      the capsule size a; our computations determine the latter dependence to be (in
      dimensionless form) h ~ a(-2) for the large capsules studied in this work. For
      small and moderate capsule sizes a, the capsule velocity Ux and additional
      pressure drop DeltaP+ are governed by the same scaling laws as for high-viscosity
      droplets. The velocity and additional pressure drop of large thick capsules also
      follow the dynamics of high-viscosity droplets, and are affected by the
      lubrication film thickness. The motion of our large thick capsules is
      characterized by a Ux-U ~ h ~ a(-2) approach to the undisturbed average duct
      velocity and an additional pressure drop DeltaP+ ~a(3)/h ~ a(5). By combining
      basic physical principles and geometric properties, we develop a theoretical
      analysis that explains the power laws we found for large capsules.

PMID- 21867213
TI  - Effects of glial release and somatic receptors on bursting in synchronized
      neuronal networks.
AB  - A model is constructed to study the phenomenon of bursting in cultured neuronal
      networks by considering the effects of glial release and the extrasynaptic
      receptors on neurons. In the frequently observed situations of synchronized
      bursting, the whole neuronal network can be described by a mean-field model. In
      this model, the dynamics of the synchronized network in the presence of glia is
      represented by an effective two-compartment neuron with stimulations on both the
      dendrite and soma. Numerical simulations of this model show that most of the
      experimental observations in bursting, in particular the high plateau and the
      slow repolarization, can be reproduced. Our findings suggest that the effects of
      glia release and extrasynaptic receptors, which are usually neglected in neuronal
      models, can become important in intense network activities. Furthermore,
      simulations of the model are also performed for the case of glia-suppressed
      cultures to compare with recent experimental results.

PMID- 21867214
TI  - Electrostatics of the protein-water interface and the dynamical transition in
      proteins.
AB  - Atomic displacements of hydrated proteins are dominated by phonon vibrations at
      low temperatures and by dissipative large-amplitude motions at high temperatures.
      A crossover between the two regimes is known as a dynamical transition. Recent
      experiments indicate a connection between the dynamical transition and the
      dielectric response of the hydrated protein. We analyze two mechanisms of the
      coupling between the protein atomic motions and the protein-water interface. The
      first mechanism considers viscoelastic changes in the global shape of the protein
      plasticized by its coupling to the hydration shell. The second mechanism involves
      modulations of the local motions of partial charges inside the protein by
      electrostatic fluctuations. The model is used to analyze mean-square
      displacements of iron of metmyoglobin reported by Mossbauer spectroscopy. We show
      that high displacement of heme iron at physiological temperatures is dominated by
      electrostatic fluctuations. Two onsets, one arising from the viscoelastic
      response and the second from electrostatic fluctuations, are seen in the
      temperature dependence of the mean-square displacements when the corresponding
      relaxation times enter the instrumental resolution window.

PMID- 21867215
TI  - Effectiveness of Phi-value analysis in the binding process of Arc repressor
      dimer.
AB  - Phi-value analysis has proved to be a powerful technique in protein folding
      studies. It has been used to study the transition state structures, to infer
      microscopic folding pathways, and to identify key residues in the protein folding
      process. However, its effectiveness in protein binding reaction has not been
      tested, especially when a fly-casting mechanism is involved. In this article we
      attempt to answer this question through a coarse-grained study of the binding
      reaction of Arc repressor dimer. Our simulations show that its binding process
      proceeds through a fly-casting mechanism, consistent with previous results. We
      then estimate the importance of the residues for the fly-casting binding by
      computationally mutating each of them into glycine and calculating their
      respective effects on the capture radius. It is found that (1) the residues with
      high Phi values may not be responsible for the large capture radius in the fly
      casting binding; (2) mutation of residues with low Phi values may destabilize the
      denatured states and then increase the capture radius, presumably further
      increasing the binding rate. Based on our simulations, we conclude that Phi
      values do not reflect well the importance of residues in the fly-casting binding
      reaction and need to be combined with other techniques to provide a complete
      picture.

PMID- 21867216
TI  - Coexistence of tight and loose bundled states in a model of bacterial flagellar
      dynamics.
AB  - Many microorganisms propel themselves through their fluid environment by means of
      multiple rotating flagella that self-organize to form bundles, a process that is
      complex and poorly understood. In the present work, the bundling behavior of a
      pair of flexible flagella, each driven by a constant torque motor, is
      investigated, using a mathematical model incorporating the fluid motion generated
      by each flagellum as well as the finite flexibility of the flagella. The initial
      stage of bundling is driven purely by hydrodynamics but the final state of the
      bundle is determined by a nontrivial balance between hydrodynamics and
      elasticity. As the flexibility of the flagella increases a regime is found where,
      depending on initial conditions, one finds bundles that are either tight, with
      the flagella in mechanical contact, or loose, with the flagella intertwined but
      not touching. That is, multiple coexisting states of bundling are found. The
      parameter regime (in terms of flexibility and distance between motors) at which
      this multiplicity occurs is comparable to the parameters for a number of
      bacteria.

PMID- 21867217
TI  - Interplay between energetics and dynamics in bacterial motility.
AB  - We study how self-propelled organisms administer their energetic resources in
      order to optimize space exploration. Noting the existence of two very different
      time scales, we use a quasistatic approximation to analyze the relation between
      bacterial dynamics and changes in the energy stored by a bacterium. We then find
      both steady-state and time-dependent solutions for the bacterial speed and stored
      energy. The model also predicts the volume of the region that a bacterium may
      visit in a resource-depleted medium.

PMID- 21867218
TI  - Effect of cell and microvillus mechanics on the transmission of applied loads to
      single bonds in dynamic force spectroscopy.
AB  - Receptor-ligand interactions that mediate cellular adhesion are often subjected
      to forces that regulate their detachment via modulating off-rates. Although the
      dynamics of detachment is primarily controlled by the physical chemistry of
      adhesion molecules, cellular features such as cell deformability and microvillus
      viscoelasticity have been shown to affect the rolling velocity of leukocytes in
      vitro through experiments and simulation. In this work, we demonstrate via
      various micromechanical models of two cells adhered by a single (intramolecular)
      bond that cell deformability and microvillus viscoelasticity modulate
      transmission of an applied external load to an intramolecular bond, and thus the
      dynamics of detachment. Specifically, it is demonstrated that the intermolecular
      bond force is not equivalent to the instantaneous applied force and that the
      instantaneous bond force decreases with cellular and microvillus compliance. As
      cellular compliance increases, not only does the time lag between the applied
      load and the bond force increase, an initial response time is observed during
      which cell deformation is observed without transfer of force to the bond. It is
      further demonstrated that following tether formation the instantaneous
      intramoleular bond force increases linearly at a rate dependent on microvillus
      viscosity. Monte Carlo simulations with fixed kinetic parameters predict that
      both cell and microvillus compliance increase the average rupture time, although
      the average rupture force based on bond length remains nearly unchanged.

PMID- 21867219
TI  - Oscillatory tank-treading motion of erythrocytes in shear flows.
AB  - In this paper, we investigate the oscillatory dynamics of the tank-treading
      motion of healthy human erythrocytes in shear flows with capillary number Ca =
      O(1) and small to moderate viscosity ratios 0.01 <= lambda <= 1.5. These
      conditions correspond to a wide range of surrounding medium viscosities (4-600 m
      Pa s) and shear flow rates (2-560 s(-1)), and match those used in ektacytometry
      systems. For a given viscosity ratio, as the flow rate increases, the steady
      state erythrocyte length L (in the shear plane) increases logarithmically while
      its depth W (normal to the shear plane) decreases logarithmically. In addition,
      the flow rate increase dampens the oscillatory erythrocyte inclination but not
      its length oscillations (which show relative variations of about 5-8%). For a
      given flow rate, as the viscosity ratio increases, the erythrocyte length L
      contracts while its depth W increases (i.e., the cell becomes less deformed) with
      a small decrease in the length variations. The average orientation angle of the
      erythrocyte shows a significant decrease with the viscosity ratio as does the
      angle oscillation while the oscillation period increases. These trends continue
      in higher viscosity ratios resulting eventually in the transition from a (weakly
      oscillatory) tank-treading motion to a tumbling motion. Our computations show
      that the erythrocyte width S, which exists in the shear plane, is practically
      invariant in time, capillary number, and viscosity ratio, and corresponds to a
      real cell thickness of about 2.5 MUm. Comparison of our computational results
      with the predictions of (low degree-of-freedom) theoretical models and
      experimental findings, suggests that the energy dissipation due to the shape
      memory effects is more significant than the energy dissipation due to the
      membrane viscosity. Our work shows that the oscillatory tank-treading motion can
      account for more than 50% of the variations found in ektacytometry systems; thus,
      researchers who wish to study inherent differences between erythrocytes within a
      population must devise a way of monitoring individual cells over time so that
      they can remove the oscillation effects.

PMID- 21867220
TI  - Motor-driven dynamics of cytoskeletal filaments in motility assays.
AB  - We model analytically the dynamics of a cytoskeletal filament in a motility
      assay. The filament is described as rigid rod free to slide in two dimensions.
      The motor proteins consist of polymeric tails tethered to the plane and modeled
      as linear springs and motor heads that bind to the filament. As in related models
      of rigid and soft two-state motors, the binding and unbinding dynamics of the
      motor heads and the dependence of the transition rates on the load exerted by the
      motor tails play a crucial role in controlling the filament's dynamics. Our work
      shows that the filament effectively behaves as a self-propelled rod at long
      times, but with non-Markovian noise sources arising from the coupling to the
      motor binding and unbinding dynamics. The effective propulsion force of the
      filament and the active renormalization of the various friction and diffusion
      constants are calculated in terms of microscopic motor and filament parameters.
      These quantities could be probed by optical force microscopy.

PMID- 21867221
TI  - Optical response of a disordered bicontinuous macroporous structure in the
      longhorn beetle Sphingnotus mirabilis.
AB  - We studied the structural and optical properties of scales in the longhorn beetle
      Sphingnotus mirabilis. Structural characterizations revealed that the scale
      interior possesses a disordered bicontinuous macroporous structure, resembling a
      phase-separated structure obtained by spinodal decomposition. Its optical
      response was investigated both experimentally and theoretically. Our results show
      that this structure has interesting optical properties due to the existence of
      only short-range order and the lack of well-defined local structures.

PMID- 21867222
TI  - Automatic recovery of missing amplitudes and phases in tilt-limited electron
      crystallography of two-dimensional crystals.
AB  - Electron crystallography of 2D protein crystals provides a powerful tool for the
      determination of membrane protein structure. In this method, data is acquired in
      the Fourier domain as randomly sampled, uncoupled, amplitudes and phases. Due to
      physical constraints on specimen tilting, those Fourier data show a vast un
      sampled "missing cone" of information, producing resolution loss in the direction
      perpendicular to the membrane plane. Based on the flexible language of projection
      onto sets, we provide a full solution for these problems with a projective
      constraint optimization algorithm that, for sufficiently oversampled data,
      produces complete recovery of unmeasured data in the missing cone. We apply this
      method to an experimental data set of Bacteriorhodopsin and show that, in
      addition to producing superior results compared to traditional reconstruction
      methods, full, reproducible, recovery of the missing cone from noisy data is
      possible. Finally, we present an automatic implementation of the refinement
      routine as open source, freely distributed, software that will be included in our
      2dx software package.

PMID- 21867223
TI  - Recognizing nucleotides by cross-tunneling currents for DNA sequencing.
AB  - Using first-principles calculations, we study electron transport through
      nucleotides inside a rectangular nanogap formed by two pairs of gold electrodes
      which are perpendicular and parallel to the nucleobase plane. We propose that
      this setup will enhance the nucleotide selectivity of tunneling signals to a
      great extent. Information from three electrical probing processes offers full
      nucleotide recognition, which survives the noise from neighboring nucleotides and
      configuration fluctuations.

PMID- 21867224
TI  - Perturbation analysis of spontaneous action potential initiation by stochastic
      ion channels.
AB  - A stochastic interpretation of spontaneous action potential initiation is
      developed for the Morris-Lecar equations. Initiation of a spontaneous action
      potential can be interpreted as the escape from one of the wells of a double well
      potential, and we develop an asymptotic approximation of the mean exit time using
      a recently developed quasistationary perturbation method. Using the fact that the
      activating ionic channel's random openings and closings are fast relative to
      other processes, we derive an accurate estimate for the mean time to fire an
      action potential (MFT), which is valid for a below-threshold applied current.
      Previous studies have found that for above-threshold applied current, where there
      is only a single stable fixed point, a diffusion approximation can be used. We
      also explore why different diffusion approximation techniques fail to estimate
      the MFT.

PMID- 21867225
TI  - Rate response of neurons subject to fast or frozen noise: from stochastic and
      homogeneous to deterministic and heterogeneous populations.
AB  - The response of a neuronal population to afferent drive can be expected to be
      sensitive to both the distribution and dynamics of membrane voltages within the
      population. Voltage fluctuations can be driven by synaptic noise,
      neuromodulators, or cellular inhomogeneities: processes ranging from millisecond
      autocorrelation times to effectively static or "frozen" noise. Here we extend
      previous studies of filtered fluctuations to the experimentally verified
      exponential integrate-and-fire model. How fast or frozen fluctuations affect the
      steady-state rate and firing-rate response are both examined using perturbative
      solutions and limits of a 1 + 2 dimensional Fokker-Planck equation. The central
      finding is that, under conditions of a more-or-less constant population voltage
      variance, the firing-rate response is only weakly dependent on the fluctuation
      filter constant: The voltage distribution is the principal determinant of the
      population response. This result is unexpected given the nature of the systems
      underlying the extreme limits of fast and frozen fluctuations; the first limit
      represents a homogeneous population of neurons firing stochastically, whereas the
      second limit is equivalent to a heterogeneous population of neurons firing
      deterministically.

PMID- 21867226
TI  - Nature of the vibron self-trapped states in hydrogen-bonded macromolecular
      chains.
AB  - We study the influence of temperature and the values of basic energy parameters
      on the character of vibron self-trapped states in quasi-one-dimensional hydrogen
      bonded molecular chains. Investigations have been carried out within the one
      dimensional Holstein molecular crystal model employing the variational extension
      of the Lang-Firsov unitary transformation. It was found that, in the low
      temperature regime, only partially dressed small-polaron states may exist. With
      the rise of temperature, the system enters the metastability region, where
      partially dressed (light and mobile) and fully dressed (heavy and practically
      immobile) small-polaron states may exist simultaneously.

PMID- 21867227
TI  - Signal, noise, and resolution in correlated fluctuations from snapshot small
      angle x-ray scattering.
AB  - It has been suggested that the three-dimensional structure of one particle may be
      reconstructed using the scattering from many identical, randomly oriented copies
      ab initio, without modeling or a priori information. This may be possible if
      these particles are frozen in either space or time, so that the conventional two
      dimensional small-angle x-ray scattering (SAXS) distribution contains
      fluctuations and is no longer isotropic. We consider the magnitude of the
      correlated fluctuation SAXS (CFSAXS) signal for typical x-ray free-electron laser
      (XFEL) beam conditions and compare this against the errors derived with the
      inclusion of Poisson photon counting statistics. The resulting signal-to-noise
      ratio (SNR) is found to rapidly approach a limit independent of the number of
      particles contributing to each diffraction pattern, so that the addition of more
      particles to a "single-particle-per-shot" experiment may be of little value,
      apart from reducing solvent background. When the scattering power is
      significantly less than one photon per particle per Shannon pixel, the SNR grows
      in proportion to incident flux. We provide simulations for protein molecules in
      support of these analytical results, and discuss the effects of solvent
      background scatter. We consider the SNR dependence on resolution and particle
      size, and discuss the application of the method to glasses and liquids, and the
      implications of more powerful XFELs, smaller focused beams, and higher pulse
      repetition rates for this approach. We find that an accurate CFSAXS measurement
      may be acquired to subnanometer resolution for protein molecules if a 9-keV beam
      containing 10(13) photons is focused to a ~100-nm spot diameter, provided that
      the effects of solvent background can be reduced sufficiently.

PMID- 21867228
TI  - Dielectric response of particles in flowing media: the effect of shear-induced
      rotation on the variation in particle polarizability.
AB  - When particles in liquid suspensions flow through channels and pipes in a laminar
      fashion, the resulting parabolic velocity profile gives rise to shear, which
      induces the particles to rotate. If flowing suspensions containing dielectric
      particles are immersed in an external electric field, the anisotropic
      polarization induced in rotating nonspherical particles will vary with the
      orientation of the particle with respect to the external field; what results is
      an uncertainty in experimental measurements that involve particle polarization.
      The present study establishes the limits of this uncertainty and shows that
      departure from spherical symmetry in individual particles can lead to a
      significant overlap in measurements attempting to discriminate between particle
      subpopulations in suspensions. For example, the uncertainty in signal amplitude
      for a population of activated T-lymphocytes can be as high as 20%. Such concerns
      arise in applications like field-flow fractionation, dielectrophoretic sorting of
      particles, flow impedance measurements and cytometry, and, most recently,
      isodielectric separation, all of which are used to separate particles in a flow
      based on their dielectric response. This paper considers axisymmetric particles
      as the first departure from the approximation of spherical symmetry, shows how to
      calculate an estimate of the size of the population overlap, and suggests
      possible strategies to minimize it.

PMID- 21867229
TI  - Suprathreshold stochastic resonance in neural processing tuned by correlation.
AB  - Suprathreshold stochastic resonance (SSR) is examined in the context of integrate
      and-fire neurons, with an emphasis on the role of correlation in the neuronal
      firing. We employed a model based on a network of spiking neurons which received
      synaptic inputs modeled by Poisson processes stimulated by a stepped input
      signal. The smoothed ensemble firing rate provided an output signal, and the
      mutual information between this signal and the input was calculated for networks
      with different noise levels and different numbers of neurons. It was found that
      an SSR effect was present in this context. We then examined a more biophysically
      plausible scenario where the noise was not controlled directly, but instead was
      tuned by the correlation between the inputs. The SSR effect remained present in
      this scenario with nonzero noise providing improved information transmission, and
      it was found that negative correlation between the inputs was optimal. Finally,
      an examination of SSR in the context of this model revealed its connection with
      more traditional stochastic resonance and showed a trade-off between
      supratheshold and subthreshold components. We discuss these results in the
      context of existing empirical evidence concerning correlations in neuronal
      firing.

PMID- 21867230
TI  - Stochastic phase transition operator.
AB  - In this study a Markov operator is introduced that represents the density
      evolution of an impulse-driven stochastic biological oscillator. The operator's
      stochastic kernel is constructed using the asymptotic expansion of stochastic
      processes instead of solving the Fokker-Planck equation. The Markov operator is
      shown to successfully approximate the density evolution of the biological
      oscillator considered. The response of the oscillator to both periodic and time
      varying impulses can be analyzed using the operator's transient and stationary
      properties. Furthermore, an unreported stochastic dynamic bifurcation for the
      biological oscillator is obtained by using the eigenvalues of the product of the
      Markov operators.

PMID- 21867231
TI  - Accumulation of beneficial mutations in one dimension.
AB  - When beneficial mutations are relatively common, competition between multiple
      unfixed mutations can reduce the rate of fixation in well-mixed asexual
      populations. We introduce a one-dimensional model with a steady accumulation of
      beneficial mutations. We find a transition between periodic selection and
      multiple-mutation regimes. In the multiple-mutation regime, the increase of
      fitness along the lattice bears a striking similarity to surface growth
      phenomena, with power-law growth and saturation of the interface width. We also
      find significant differences compared to the well-mixed model. In our lattice
      model, the transition between regimes happens at a much lower mutation rate due
      to slower fixation times in one dimension. Also, the rate of fixation is reduced
      with increasing mutation rate due to the more intense competition, and it
      saturates with large population size.

PMID- 21867232
TI  - Electromechanical effects on multilayered cells in nonuniform rotating fields.
AB  - We use the Maxwell stress tensor to calculate the dielectrophoretic force and
      electrorotational torque acting on a realistic four-shelled model of the yeast
      Saccharomyces cerevisiae in a nonuniform rotating electric field generated by
      four coplanar square electrodes. The comparison of these results with numerical
      calculations of the dipolar and quadrupolar contributions obtained from an
      integral equation for the polarization charge density shows the effect of the
      quadrupole contribution in the proximity of the electrode plane. We also show
      that under typical experimental conditions the substitution of the multilayered
      cell by an equivalent cell with homogeneous permittivity underestimates the
      quadrupole contribution to the force and torque by 1 order of magnitude.

PMID- 21867233
TI  - Growth states of catalytic reaction networks exhibiting energy metabolism.
AB  - All cells derive nutrition by absorbing some chemical and energy resources from
      the environment; these resources are used by the cells to reproduce the chemicals
      within them, which in turn leads to an increase in their volume. In this study we
      introduce a protocell model exhibiting catalytic reaction dynamics, energy
      metabolism, and cell growth. Results of extensive simulations of this model show
      the existence of four phases with regard to the rates of both the influx of
      resources and cell growth. These phases include an active phase with high influx
      and high growth rates, an inefficient phase with high influx but low growth
      rates, a quasistatic phase with low influx and low growth rates, and a death
      phase with negative growth rate. A mean field model well explains the transition
      among these phases as bifurcations. The statistical distribution of the active
      phase is characterized by a power law, and that of the inefficient phase is
      characterized by a nearly equilibrium distribution. We also discuss the relevance
      of the results of this study to distinct states in the existing cells.

PMID- 21867234
TI  - Monodisperse domains by proteolytic control of the coarsening instability.
AB  - The coarsening instability typically disrupts steady-state cluster-size
      distributions. We show that degradation coupled to the cluster size, such as
      arising from biological proteolysis, leads to a fixed-point cluster size.
      Stochastic evaporative and condensative fluxes determine the width of the fixed
      point size distribution. At the fixed point, we show how the peak size and width
      depend on number, interactions, and proteolytic rate. This proteolytic size
      control mechanism is consistent with the phenomenology of pseudopilus length
      control in the general secretion pathway of bacteria.

PMID- 21867235
TI  - Information from time-forward and time-backward processes in Szilard engines.
AB  - We derive the work performed in the Szilard engine (SZE) by using the dissipative
      work formula of nonequilibrium thermodynamics developed by Kawai et al. [Phys.
      Rev. Lett. 98, 080602 (2007)]. The work is described as the difference of
      probability distributions of measurement outcomes of the time-forward and the
      time-backward process.

PMID- 21867236
TI  - Solution of Fokker-Planck equation for a broad class of drift and diffusion
      coefficients.
AB  - A Langevin equation with variable drift and diffusion coefficients separable in
      time and space and its corresponding Fokker-Planck equation in the Stratonovich
      approach are considered. From this Fokker-Planck equation a class of exact
      solutions with the same spatial drift and diffusion coefficients is obtained.
      Furthermore, some details of this system are analyzed by using the spatial
      diffusion coefficient D(x) = sqrt[D]|x|(-theta/2).

PMID- 21867237
TI  - Transport coefficients of driven granular fluids at moderate volume fraction.
AB  - In a recent publication [Phys. Rev. E 83, 011301 (2011)], Vollmayr-Lee et al.
      have determined by computer simulations the thermal diffusivity and the
      longitudinal viscosity coefficients of a driven granular fluid of hard spheres at
      intermediate volume fractions. Although they compare their simulation results
      with the predictions of kinetic theory, they use the dilute expressions for the
      driven system and the modified Sonine approximations for the undriven system. The
      goal here is to carry out this comparison by proposing a modified Sonine
      approximation to the Enskog equation for driven granular fluids that leads to a
      better quantitative agreement.

PMID- 21867238
TI  - Elastic response of binary hard-sphere fluids.
AB  - We derive expressions for the high-frequency, wave-number-dependent elastic
      constants of a binary hard-sphere fluid and employ Monte Carlo computer
      simulation to evaluate these constants in order to highlight the impact of
      composition and relative sphere diameter on the elastic response of this system.
      It is found that the elastic constant c(11)(k) exhibits oscillatory behavior as a
      function of k whereas the high-frequency shear modulus, for example, does not.
      This behavior is shown to be dictated by the angular dependence (in k[over ?]
      space) of derivatives of the interatomic force at contact. The results are
      related to recent measurements of the compressibility of colloidal fluids in
      laser trapping experiments.

PMID- 21867239
TI  - Steric-effect-induced enhancement of electrical-double-layer overlapping
      phenomena.
AB  - In this paper, we demonstrate that nontrivial interactions between steric effect
      and electrical-double-layer (EDL) overlap phenomena may augment the effective
      extent of EDL overlap in narrow fluidic confinements to a significant extent by
      virtue of rendering the channel centerline potential tending to the zeta
      potential in a limiting sense as the steric effect progressively intensifies.
      Such a behavior may result in a virtually uniform (undiminished) magnitude of the
      EDL potential across the entire channel height and may cause lowering of the
      total charge within the EDL.

PMID- 21867240
TI  - Aerodynamic trick for visual stabilization during downstroke in a hovering bird.
AB  - We provide physical insight into how a small hovering bird attains stabilized
      vision during downstroke. A passerine generates a lift force greater than its
      body weight during downstroke, leading to a substantial swing of the bird body,
      but the bird's eyes are nearly stable. Employing digital particle-image
      velocimetry, we demonstrate that a hovering passerine generates a lift force
      acting dorsal to the center of mass, concurrently resulting in rotational and
      translational displacements of the bird's body. The most notable finding is that
      the rotational and translational displacements at the bird's eyes almost cancel
      each other; the displacement of the eye is ~8% that of the trailing tip of the
      tail. This aerodynamic trick enables a bird to attain stabilized vision
      beneficial for the inspection of the environment.

PMID- 21867241
TI  - Spontaneous motion of a droplet coupled with a chemical wave.
AB  - We propose a framework for the spontaneous motion of a droplet coupled with
      internal dynamic patterns generated in a reaction-diffusion system. The
      spatiotemporal order of the chemical reaction gives rise to inhomogeneous surface
      tension and results in self-propulsion driven by the surrounding flow due to the
      Marangoni effect. Numerical calculations of internal patterns together with
      theoretical results of the flow fields at low Reynolds number reproduce well the
      experimental results obtained using a droplet of the Belousov-Zhabotinsky
      reaction medium.

PMID- 21867242
TI  - Role of modulus mismatch on crack propagation and toughness enhancement in
      bioinspired composites.
AB  - Natural materials such as nacre exhibit a high resistance to crack propagation,
      inspiring the development of artificial composites imitating the structure of
      these biological composites. We use a phase field approach to study the role
      played by the elastic modulus mismatch between stiff and soft layers on crack
      propagation in such bioinspired composites. Our simulations show that the
      introduction of a thin layer of a soft phase in a stiff matrix can lead to arrest
      of a propagating crack and can also lead to crack branching. The crack branching
      observed in the phase field model is analyzed using a cohesive zone approach.
      Further, we show that the toughness of such a composite can be substantially
      higher than that of its constituents.

PMID- 21867243
TI  - Update rules and interevent time distributions: slow ordering versus no ordering
      in the voter model.
AB  - We introduce a general methodology of update rules accounting for arbitrary
      interevent time (IET) distributions in simulations of interacting agents. We
      consider in particular update rules that depend on the state of the agent, so
      that the update becomes part of the dynamical model. As an illustration we
      consider the voter model in fully connected, random, and scale-free networks with
      an activation probability inversely proportional to the time since the last
      action, where an action can be an update attempt (an exogenous update) or a
      change of state (an endogenous update). We find that in the thermodynamic limit,
      at variance with standard updates and the exogenous update, the system orders
      slowly for the endogenous update. The approach to the absorbing state is
      characterized by a power-law decay of the density of interfaces, observing that
      the mean time to reach the absorbing state might be not well defined. The IET
      distributions resulting from both update schemes show power-law tails.

PMID- 21867244
TI  - Chimera states are chaotic transients.
AB  - Spatiotemporal chaos and turbulence are universal concepts for the explanation of
      irregular behavior in various physical systems. Recently, a remarkable new
      phenomenon, called "chimera states," has been described, where in a spatially
      homogeneous system, regions of irregular incoherent motion coexist with regular
      synchronized motion, forming a self-organized pattern in a population of
      nonlocally coupled oscillators. Whereas most previous studies of chimera states
      focused their attention on the case of large numbers of oscillators employing the
      thermodynamic limit of infinitely many oscillators, here we investigate the
      properties of chimera states in populations of finite size using concepts from
      deterministic chaos. Our calculations of the Lyapunov spectrum show that the
      incoherent motion, which is described in the thermodynamic limit as a stationary
      behavior, in finite size systems appears as weak spatially extensive chaos.
      Moreover, for sufficiently small populations the chimera states reveal their
      transient nature: after a certain time span we observe a sudden collapse of the
      chimera pattern and a transition to the completely coherent state. Our results
      indicate that chimera states can be considered as chaotic transients, showing the
      same properties as type-II supertransients in coupled map lattices.

PMID- 21867245
TI  - Dynamic effects induced by renormalization in anisotropic pattern forming
      systems.
AB  - The dynamics of patterns in large two-dimensional domains remains a challenge in
      nonequilibrium phenomena. Often it is addressed through mild extensions of one
      dimensional equations. We show that full two-dimensional generalizations of the
      latter can lead to unexpected dynamic behavior. As an example we consider the
      anisotropic Kuramoto-Sivashinsky equation, which is a generic model of
      anisotropic pattern forming systems and has been derived in different instances
      of thin film dynamics. A rotation of a ripple pattern by 90 degrees  occurs in
      the system evolution when nonlinearities are strongly suppressed along one
      direction. This effect originates in nonlinear parameter renormalization at
      different rates in the two system dimensions, showing a dynamic interplay between
      scale invariance and wavelength selection. Potential experimental realizations of
      this phenomenon are identified.

PMID- 21867246
TI  - Stability of ring patterns arising from two-dimensional particle interactions.
AB  - Pairwise particle interactions arise in diverse physical systems ranging from
      insect swarms to self-assembly of nanoparticles. In the presence of long-range
      attraction and short-range repulsion, such systems can exhibit bound states. We
      use linear stability analysis of a ring equilibrium to classify the morphology of
      patterns in two dimensions. Conditions are identified that assure the well
      posedness of the ring. In addition, weakly nonlinear theory and numerical
      simulations demonstrate how a ring can bifurcate to more complex equilibria
      including triangular shapes, annuli, and spot patterns with N-fold symmetry. Many
      of these patterns have been observed in nature, although a general theory has
      been lacking, in particular how small changes to the interaction potential can
      lead to large changes in the self-organized state.

PMID- 21867247
TI  - Persistence of incomplete mixing: a key to anomalous transport.
AB  - Anomalous dispersion in heterogeneous environments describes the anomalous growth
      of the macroscopic characteristic sizes of scalar fields. Here we show that this
      phenomenon is closely related to the persistence of local scale incomplete
      mixing. We introduce the mixing scale epsilon as the length for which the scalar
      distribution is locally uniform. We quantify its temporal evolution due to the
      competition of shear action and diffusion and compare it to the evolution of the
      global dispersion scale sigma. In highly heterogeneous flow fields, for which the
      temporal evolution of sigma is superdiffusive, we find that epsilon evolves
      subdiffusively. The anomalous evolutions of the dispersion and mixing scales are
      complementary, epsilonsigma ? t. This result relates anomalous global dispersion
      to the dynamics of local mixing.

PMID- 21867248
TI  - Universality and scaling behavior of injected power in elastic turbulence in
      wormlike micellar gel.
AB  - We study the statistical properties of spatially averaged global injected power
      fluctuations for Taylor-Couette flow of a wormlike micellar gel formed by
      surfactant cetyltrimethylammonium tosylate. At sufficiently high Weissenberg
      numbers the shear rate, and hence the injected power p(t), at a constant applied
      stress shows large irregular fluctuations in time. The nature of the probability
      distribution function (PDF) of p(t) and the power-law decay of its power spectrum
      are very similar to that observed in recent studies of elastic turbulence for
      polymer solutions. Remarkably, these non-Gaussian PDFs can be well described by a
      universal, large deviation functional form given by the generalized Gumbel
      distribution observed in the context of spatially averaged global measures in
      diverse classes of highly correlated systems. We show by in situ rheology and
      polarized light scattering experiments that in the elastic turbulent regime the
      flow is spatially smooth but random in time, in agreement with a recent
      hypothesis for elastic turbulence.

PMID- 21867249
TI  - Structures of Yukawa and Coulomb particles in cylinders: simulations for fine
      particle plasmas and colloidal suspensions.
AB  - Low-temperature structures of Yukawa particles in systems with cylindrical
      symmetry are analyzed by numerical simulations. Particles are organized into well
      defined thin concentric shells forming triangular lattices with defects on each
      shell and structural parameters are expressed by simple interpolation formulas
      including the limiting case of Coulomb particles. In outer shells, the local
      structure can be regarded as three-dimensional closest packing as in the case of
      the background of uniform spheres. These formulas can be directly compared with
      fine particle experiments in long cylindrical chambers under microgravity or
      colloidal suspensions in cylinders and may be useful as a basis of structural
      analyses in cylindrical systems.

PMID- 21867250
TI  - Steady magnetic-field generation via surface-plasma-wave excitation.
AB  - The possibility of inducing a magnetic field via surface plasma-wave excitation
      is investigated with a simple nonrelativistic hydrodynamic model. A static
      magnetic field is predicted at the plasma surface, scaling with the square of the
      surface-wave field amplitude, and the influence of the electron plasma density is
      studied. In the case of resonant surface-wave excitation by laser this result can
      be applied to low intensities such that the electron quiver velocity in the field
      of the surface wave is less than its thermal velocity.

PMID- 21867251
TI  - Decreasing the spectral radius of a graph by link removals.
AB  - The decrease of the spectral radius, an important characterizer of network
      dynamics, by removing links is investigated. The minimization of the spectral
      radius by removing m links is shown to be an NP-complete problem, which suggests
      considering heuristic strategies. Several greedy strategies are compared, and
      several bounds on the decrease of the spectral radius are derived. The strategy
      that removes that link l=i~j with largest product (x(1))(i)(x(1))(j) of the
      components of the eigenvector x(1) belonging to the largest adjacency eigenvalue
      is shown to be superior to other strategies in most cases. Furthermore, a scaling
      law where the decrease in spectral radius is inversely proportional to the number
      of nodes N in the graph is deduced. Another sublinear scaling law of the decrease
      in spectral radius versus the number m of removed links is conjectured.

PMID- 21867252
TI  - Fractality of eroded coastlines of correlated landscapes.
AB  - Using numerical simulations of a simple sea-coast mechanical erosion model, we
      investigate the effect of spatial long-range correlations in the lithology of
      coastal landscapes on the fractal behavior of the corresponding coastlines. In
      the model, the resistance of a coast section to erosion depends on the local
      lithology configuration as well as on the number of neighboring sea sides. For
      weak sea forces, the sea is trapped by the coastline and the eroding process
      stops after some time. For strong sea forces erosion is perpetual. The transition
      between these two regimes takes place at a critical sea force, characterized by a
      fractal coastline front. For uncorrelated landscapes, we obtain, at the critical
      value, a fractal dimension D=1.33, which is consistent with the dimension of the
      accessible external perimeter of the spanning cluster in two-dimensional
      percolation. For sea forces above the critical value, our results indicate that
      the coastline is self-affine and belongs to the Kardar-Parisi-Zhang universality
      class. In the case of landscapes generated with power-law spatial long-range
      correlations, the coastline fractal dimension changes continuously with the Hurst
      exponent H, decreasing from D=1.34 to 1.04, for H=0 and 1, respectively. This
      nonuniversal behavior is compatible with the multitude of fractal dimensions
      found for real coastlines.

PMID- 21867253
TI  - Preferential attachment in growing spatial networks.
AB  - We obtain the degree distribution for a class of growing network models on flat
      and curved spaces. These models evolve by preferential attachment weighted by a
      function of the distance between nodes. The degree distribution of these models
      is similar to that of the fitness model of Bianconi and Barabasi, with a fitness
      distribution dependent on the metric and the density of nodes. We show that
      curvature singularities in these spaces can give rise to asymptotic Bose-Einstein
      condensation, but transient condensation can be observed also in smooth
      hyperbolic spaces with strong curvature. We provide numerical results for spaces
      of constant curvature (sphere, flat, and hyperbolic space) and we discuss the
      conditions for the breakdown of this approach and the critical points of the
      transition to distance-dominated attachment. Finally, we discuss the distribution
      of link lengths.

PMID- 21867254
TI  - Analytically solvable processes on networks.
AB  - We introduce a broad class of analytically solvable processes on networks. In the
      special case, they reduce to random walk and consensus process, the two most
      basic processes on networks. Our class differs from previous models of
      interactions (such as the stochastic Ising model, cellular automata, infinite
      particle systems, and the voter model) in several ways, the two most important
      being (i) the model is analytically solvable even when the dynamical equation for
      each node may be different and the network may have an arbitrary finite graph and
      influence structure and (ii) when local dynamics is described by the same
      evolution equation, the model is decomposable, with the equilibrium behavior of
      the system expressed as an explicit function of network topology and node
      dynamics.

PMID- 21867255
TI  - Path lengths, correlations, and centrality in temporal networks.
AB  - In temporal networks, where nodes interact via sequences of temporary events,
      information or resources can only flow through paths that follow the time
      ordering of events. Such temporal paths play a crucial role in dynamic processes.
      However, since networks have so far been usually considered static or
      quasistatic, the properties of temporal paths are not yet well understood.
      Building on a definition and algorithmic implementation of the average temporal
      distance between nodes, we study temporal paths in empirical networks of human
      communication and air transport. Although temporal distances correlate with
      static graph distances, there is a large spread, and nodes that appear close from
      the static network view may be connected via slow paths or not at all.
      Differences between static and temporal properties are further highlighted in
      studies of the temporal closeness centrality. In addition, correlations and
      heterogeneities in the underlying event sequences affect temporal path lengths,
      increasing temporal distances in communication networks and decreasing them in
      the air transport network.

PMID- 21867256
TI  - Multifractal detrending moving-average cross-correlation analysis.
AB  - There are a number of situations in which several signals are simultaneously
      recorded in complex systems, which exhibit long-term power-law cross
      correlations. The multifractal detrended cross-correlation analysis (MFDCCA)
      approaches can be used to quantify such cross correlations, such as the MFDCCA
      based on the detrended fluctuation analysis (MFXDFA) method. We develop in this
      work a class of MFDCCA algorithms based on the detrending moving-average
      analysis, called MFXDMA. The performances of the proposed MFXDMA algorithms are
      compared with the MFXDFA method by extensive numerical experiments on pairs of
      time series generated from bivariate fractional Brownian motions, two-component
      autoregressive fractionally integrated moving-average processes, and binomial
      measures, which have theoretical expressions of the multifractal nature. In all
      cases, the scaling exponents h(xy) extracted from the MFXDMA and MFXDFA
      algorithms are very close to the theoretical values. For bivariate fractional
      Brownian motions, the scaling exponent of the cross correlation is independent of
      the cross-correlation coefficient between two time series, and the MFXDFA and
      centered MFXDMA algorithms have comparative performances, which outperform the
      forward and backward MFXDMA algorithms. For two-component autoregressive
      fractionally integrated moving-average processes, we also find that the MFXDFA
      and centered MFXDMA algorithms have comparative performances, while the forward
      and backward MFXDMA algorithms perform slightly worse. For binomial measures, the
      forward MFXDMA algorithm exhibits the best performance, the centered MFXDMA
      algorithms performs worst, and the backward MFXDMA algorithm outperforms the
      MFXDFA algorithm when the moment order q<0 and underperforms when q>0. We apply
      these algorithms to the return time series of two stock market indexes and to
      their volatilities. For the returns, the centered MFXDMA algorithm gives the best
      estimates of h(xy)(q) since its h(xy)(2) is closest to 0.5, as expected, and the
      MFXDFA algorithm has the second best performance. For the volatilities, the
      forward and backward MFXDMA algorithms give similar results, while the centered
      MFXDMA and the MFXDFA algorithms fail to extract rational multifractal nature.

PMID- 21867257
TI  - Emergence of heterogeneity in a noncompetitive resource allocation problem.
AB  - Tuning one's shower in some hotels may turn into a challenging coordination game
      with imperfect information. The temperature sensitivity increases with the number
      of agents, making the problem possibly unlearnable. Because there is in practice
      a finite number of possible tap positions, identical agents are unlikely to reach
      even approximately their favorite water temperature. We show that a population of
      agents with homogeneous strategies is evolutionary unstable, which gives insights
      into the emergence of heterogeneity, the latter being tempting but risky.

PMID- 21867258
TI  - Penalized versions of the Newman-Girvan modularity and their relation to
      normalized cuts and k-means clustering.
AB  - Two penalized-balanced and normalized-versions of the Newman-Girvan modularity
      are introduced and estimated by the non-negative eigenvalues of the modularity
      and normalized modularity matrix, respectively. In this way, the partition of the
      vertices that maximizes the modularity can be obtained by applying the k-means
      algorithm for the representatives of the vertices based on the eigenvectors
      belonging to the largest positive eigenvalues of the modularity or normalized
      modularity matrix. The proper dimension depends on the number of the structural
      eigenvalues of positive sign, while dominating negative eigenvalues indicate an
      anticommunity structure; the balance between the negative and the positive
      eigenvalues determines whether the underlying graph has a community,
      anticommunity, or randomlike structure.

PMID- 21867259
TI  - Competition between intra-community and inter-community synchronization and
      relevance in brain cortical networks.
AB  - In this paper the effects of inter-community links on the synchronization
      performance of community networks, especially on the competition between
      individual community and the whole network, are studied in detail. The study is
      organized from two aspects: the number or portion of inter-community links and
      the connection strategy of inter-community links between different communities. A
      critical point is found in the competition of global network and individual
      communities. Increasing the number of inter-community links will enhance the
      global synchronizability but degrade the synchronization performance of
      individual community before this point. After that the individual community will
      synchronize better and better as part of the whole network because the community
      structure is not so prominent. The critical point represents a balance region
      where the individual community is maximally independent while the information
      transmission remains effective between different communities. Among various
      connection strategies, connecting nodes belonging to different communities
      randomly rather than connecting nodes with larger degrees are the most efficient
      way to enhance global synchronization of the network. However, the dynamical
      modularity is the reverse case. A preferential connection scheme linking most of
      the hubs from the communities will allow rather efficient global synchronization
      while maintaining strong dynamical clustering of the communities. Interestingly,
      the observations are found to be relevant in a realistic network of cat cortex.
      The synchronization state is just at the critical point, which shows a reasonable
      combination of segregated function in individual communities and coordination
      among them. Our work sheds light on principles underlying the emergence of
      modular architectures in real network systems and provides guidance for the
      manipulation of synchronization in community networks.

PMID- 21867260
TI  - Exact solutions for social and biological contagion models on mixed directed and
      undirected, degree-correlated random networks.
AB  - We derive analytic expressions for the possibility, probability, and expected
      size of global spreading events starting from a single infected seed for a broad
      collection of contagion processes acting on random networks with both directed
      and undirected edges and arbitrary degree-degree correlations. Our work extends
      previous theoretical developments for the undirected case, and we provide
      numerical support for our findings by investigating an example class of networks
      for which we are able to obtain closed-form expressions.

PMID- 21867261
TI  - Assessing the consistency of community structure in complex networks.
AB  - In recent years, community structure has emerged as a key component of complex
      network analysis. As more data have been collected, researchers have begun
      investigating changing community structure across multiple networks. Several
      methods exist to analyze changing communities, but most of these are limited to
      evolution of a single network over time. In addition, most of the existing
      methods are more concerned with change at the community level than at the level
      of the individual node. In this paper, we introduce scaled inclusivity, which is
      a method to quantify the change in community structure across networks. Scaled
      inclusivity evaluates the consistency of the classification of every node in a
      network independently. In addition, the method can be applied cross sectionally
      as well as longitudinally. In this paper, we calculate the scaled inclusivity for
      a set of simulated networks of United States cities and a set of real networks
      consisting of teams that play in the top division of American college football.
      We found that scaled inclusivity yields reasonable results for the consistency of
      individual nodes in both sets of networks. We propose that scaled inclusivity may
      provide a useful way to quantify the change in a network's community structure.

PMID- 21867262
TI  - Modeling the topology of protein interaction networks.
AB  - A major issue in biology is the understanding of the interactions between
      proteins. These interactions can be described by a network, where the proteins
      are modeled by nodes and the interactions by edges. The origin of these protein
      networks is not well understood yet. Here we present a two-step model, which
      generates clusters with the same topological properties as networks for protein
      protein interactions, namely, the same degree distribution, cluster size
      distribution, clustering coefficient, and shortest path length. The biological
      and model networks are not scale-free but exhibit small-world features. The model
      allows the fitting of different biological systems by tuning a single parameter.

PMID- 21867263
TI  - Fine structure of spectral properties for random correlation matrices: an
      application to financial markets.
AB  - We study some properties of eigenvalue spectra of financial correlation matrices.
      In particular, we investigate the nature of the large eigenvalue bulks which are
      observed empirically, and which have often been regarded as a consequence of the
      supposedly large amount of noise contained in financial data. We challenge this
      common knowledge by acting on the empirical correlation matrices of two data sets
      with a filtering procedure which highlights some of the cluster structure they
      contain, and we analyze the consequences of such filtering on eigenvalue spectra.
      We show that empirically observed eigenvalue bulks emerge as superpositions of
      smaller structures, which in turn emerge as a consequence of cross correlations
      between stocks. We interpret and corroborate these findings in terms of factor
      models, and we compare empirical spectra to those predicted by random matrix
      theory for such models.

PMID- 21867264
TI  - Narrow scope for resolution-limit-free community detection.
AB  - Detecting communities in large networks has drawn much attention over the years.
      While modularity remains one of the more popular methods of community detection,
      the so-called resolution limit remains a significant drawback. To overcome this
      issue, it was recently suggested that instead of comparing the network to a
      random null model, as is done in modularity, it should be compared to a constant
      factor. However, it is unclear what is meant exactly by "resolution-limit-free,"
      that is, not suffering from the resolution limit. Furthermore, the question
      remains what other methods could be classified as resolution-limit-free. In this
      paper we suggest a rigorous definition and derive some basic properties of
      resolution-limit-free methods. More importantly, we are able to prove exactly
      which class of community detection methods are resolution-limit-free.
      Furthermore, we analyze which methods are not resolution-limit-free, suggesting
      there is only a limited scope for resolution-limit-free community detection
      methods. Finally, we provide such a natural formulation, and show it performs
      superbly.

PMID- 21867265
TI  - Avalanches, precursors, and finite-size fluctuations in a mesoscopic model of
      amorphous plasticity.
AB  - We discuss avalanche and finite-size fluctuations in a mesoscopic model to
      describe the shear plasticity of amorphous materials. Plastic deformation is
      assumed to occur through series of local reorganizations. Yield stress criteria
      are random while each plastic slip event induces a quadrupolar long-range elastic
      stress redistribution. The model is discretized on a regular square lattice.
      Shear plasticity can be studied in this context as a depinning dynamic phase
      transition. We show evidence for a scale-free distribution of avalanches P(s) ?
      S(-kappa) with a nontrivial exponent kappa~1.25 significantly different from the
      mean field result kappa=1.5. Finite-size effects allow for a characterization of
      the scaling invariance of the yield stress fluctuations observed in small
      samples. We finally identify a population of precursors of plastic activity and
      characterize its spatial distribution.

PMID- 21867266
TI  - Interplay between structure and dynamics in adaptive complex networks: emergence
      and amplification of modularity by adaptive dynamics.
AB  - Many real networks display modular organization, which can influence dynamical
      clustering on the networks. Therefore, there have been proposals put forth
      recently to detect network communities by using dynamical clustering. In this
      paper, we study how the feedback from dynamical clusters can shape the network
      connection weights with a weight-adaptation scheme motivated from Hebbian
      learning in neural systems. We show that such a scheme generically leads to the
      formation of community structure in globally coupled chaotic oscillators. The
      number of communities in the adaptive network depends on coupling strength c and
      adaptation strength r. In a modular network, the adaptation scheme will enhance
      the intramodule connection weights and weaken the intermodule connection
      strengths, generating effectively separated dynamical clusters that coincide with
      the communities of the network. In this sense, the modularity of the network is
      amplified by the adaptation. Thus, for a network with a strong community
      structure, the adaptation scheme can evidently reflect its community structure by
      the resulting amplified weighted network. For a network with a weak community
      structure, the statistical properties of synchronization clusters from different
      realizations can be used to amplify the modularity of the communities so that
      they can be detected reliably by the other traditional algorithms.

PMID- 21867267
TI  - Detecting the temporal structure of intermittent phase locking.
AB  - This study explores a method to characterize the temporal structure of
      intermittent phase locking in oscillatory systems. When an oscillatory system is
      in a weakly synchronized regime away from a synchronization threshold, it spends
      most of the time in parts of its phase space away from the synchronization state.
      Therefore characteristics of dynamics near this state (such as its stability
      properties and Lyapunov exponents or distributions of the durations of
      synchronized episodes) do not describe the system's dynamics for most of the
      time. We consider an approach to characterize the system dynamics in this case by
      exploring the relationship between the phases on each cycle of oscillations. If
      some overall level of phase locking is present, one can quantify when and for how
      long phase locking is lost, and how the system returns back to the phase-locked
      state. We consider several examples to illustrate this approach: coupled skewed
      tent maps, the stability of which can be evaluated analytically; coupled Rossler
      and Lorenz oscillators, undergoing through different intermittency types on the
      way to phase synchronization; and a more complex example of coupled neurons. We
      show that the obtained measures can describe the differences in the dynamics and
      temporal structure of synchronization and desynchronization events for the
      systems with a similar overall level of phase locking and similar stability of
      the synchronized state.

PMID- 21867268
TI  - Clustering of extreme and recurrent events in deterministic chaotic systems.
AB  - We study the nontrivial clustering properties of extreme or recurrent events in
      the context of deterministic chaotic systems. We find that correlations between
      return times of such events can depend nonmonotonically on the threshold used to
      define the events, which leads to counterintuitive behavior. In particular, the
      distribution of the conditional return intervals can indicate clustering as well
      as repelling of extreme events for the same condition but different thresholds-in
      sharp contrast to what has been observed for stochastic processes with long-range
      correlations as well as for independent and identically distributed random
      variables. This has important implications for the time-dependent hazard
      assessment of extreme events, indicating that possible threshold dependencies
      should always be taken into account.

PMID- 21867269
TI  - Improved unfolding by detrending of statistical fluctuations in quantum spectra.
AB  - A fundamental relation exists between the statistical properties of the
      fluctuations of the energy-level spectrum of a Hamiltonian and the chaotic
      properties of the physical system it describes. This relationship has been
      addressed previously as a signature of chaos in quantum dynamical systems. In
      order to properly analyze these fluctuations, however, it is necessary to
      separate them from the general tendency, namely, its secular part. Unfortunately
      this process, called unfolding, is not trivial and can lead to erroneous
      conclusions about the chaoticity of a system. In this paper we propose a
      technique to improve the unfolding procedure for the purpose of minimizing the
      dependence on the particular procedure. This technique is based on detrending the
      fluctuations of the unfolded spectra through the empirical mode decomposition
      method.

PMID- 21867270
TI  - Swift-Hohenberg equation with broken cubic-quintic nonlinearity.
AB  - The cubic-quintic Swift-Hohenberg equation (SH35) provides a convenient order
      parameter description of several convective systems with reflection symmetry in
      the layer midplane, including binary fluid convection. We use SH35 with an
      additional quadratic term to determine the qualitative effects of breaking the
      midplane reflection symmetry on the properties of spatially localized structures
      in these systems. Our results describe how the snakes-and-ladders organization of
      localized structures in SH35 deforms with increasing symmetry breaking and show
      that the deformation ultimately generates the snakes-and-ladders structure
      familiar from the quadratic-cubic Swift-Hohenberg equation. Moreover, in
      nonvariational systems, such as convection, odd-parity convectons necessarily
      drift when the reflection symmetry is broken, permitting collisions among moving
      localized structures. Collisions between both identical and nonidentical
      traveling states are described.

PMID- 21867271
TI  - Nonlinear waves in disordered chains: probing the limits of chaos and spreading.
AB  - We probe the limits of nonlinear wave spreading in disordered chains which are
      known to localize linear waves. We particularly extend recent studies on the
      regimes of strong and weak chaos during subdiffusive spreading of wave packets
      [Europhys. Lett. 91, 30001 (2010)] and consider strong disorder, which favors
      Anderson localization. We probe the limit of infinite disorder strength and study
      Frohlich-Spencer-Wayne models. We find that the assumption of chaotic wave packet
      dynamics and its impact on spreading is in accord with all studied cases.
      Spreading appears to be asymptotic, without any observable slowing down. We also
      consider chains with spatially inhomogeneous nonlinearity, which give further
      support to our findings and conclusions.

PMID- 21867272
TI  - Domain wall dynamics in integrable and chaotic spin-1/2 chains.
AB  - We study the time evolution of correlation functions, spin current, and local
      magnetization in an isolated spin-1/2 chain initially prepared in a sharp domain
      wall state. The results are compared with the level of spatial delocalization of
      the eigenstates of the system which is measured using the inverse participation
      ratio. Both integrable and nonintegrable regimes are considered. Nonintegrability
      is introduced to the integrable Hamiltonian with nearest-neighbor couplings by
      adding a single-site impurity field or by adding next-nearest-neighbor couplings.
      A monotonic correspondence between the enhancement of the level of
      delocalization, spin current, and magnetization dynamics occurs in the integrable
      domain. This correspondence is, however, lost for chaotic models with weak Ising
      interactions.

PMID- 21867273
TI  - Regulating drift-wave plasma turbulence into spatiotemporal patterns by pinning
      coupling.
AB  - Using the technique of pinning coupling in chaos control, we investigate how the
      two-dimensional drift-wave plasma turbulence described by the Hasegawa-Mima
      equation can be regulated into different spatiotemporal patterns. It is shown
      both analytically and numerically that, depending on the pattern structure of the
      target, the pinning strength necessary for regulating the turbulence could have a
      large variation. More specifically, with the increase of the wave number of the
      target, the critical pinning strength is found to be increased by a power-law
      scaling. Moreover, in both the transition and transient process of the pinning
      regulation, the modes of the turbulence are found to be suppressed in a
      hierarchical fashion, that is, by the sequence of mode wave number. The findings
      give insight into the dynamics of drift-wave turbulence, as well as indicative to
      the design of new control techniques for real-world turbulence.

PMID- 21867274
TI  - Arbitrary-order Hilbert spectral analysis for time series possessing scaling
      statistics: comparison study with detrended fluctuation analysis and wavelet
      leaders.
AB  - In this paper we present an extended version of Hilbert-Huang transform, namely
      arbitrary-order Hilbert spectral analysis, to characterize the scale-invariant
      properties of a time series directly in an amplitude-frequency space. We first
      show numerically that due to a nonlinear distortion, traditional methods require
      high-order harmonic components to represent nonlinear processes, except for the
      Hilbert-based method. This will lead to an artificial energy flux from the low
      frequency (large scale) to the high-frequency (small scale) part. Thus the power
      law, if it exists, is contaminated. We then compare the Hilbert method with
      structure functions (SF), detrended fluctuation analysis (DFA), and wavelet
      leader (WL) by analyzing fractional Brownian motion and synthesized multifractal
      time series. For the former simulation, we find that all methods provide
      comparable results. For the latter simulation, we perform simulations with an
      intermittent parameter MU=0.15. We find that the SF underestimates scaling
      exponent when q>3. The Hilbert method provides a slight underestimation when q>5.
      However, both DFA and WL overestimate the scaling exponents when q>5. It seems
      that Hilbert and DFA methods provide better singularity spectra than SF and WL.
      We finally apply all methods to a passive scalar (temperature) data obtained from
      a jet experiment with a Taylor's microscale Reynolds number Re(lambda)?250. Due
      to the presence of strong ramp-cliff structures, the SF fails to detect the power
      law behavior. For the traditional method, the ramp-cliff structure causes a
      serious artificial energy flux from the low-frequency (large scale) to the high
      frequency (small scale) part. Thus DFA and WL underestimate the scaling
      exponents. However, the Hilbert method provides scaling exponents xi(theta)(q)
      quite close to the one for longitudinal velocity, indicating a less intermittent
      passive scalar field than what was believed before.

PMID- 21867275
TI  - Scaling properties of weakly nonlinear coefficients in the Faraday problem.
AB  - Interesting and exotic surface wave patterns have regularly been observed in the
      Faraday experiment. Although symmetry arguments provide a qualitative explanation
      for the selection of some of these patterns (e.g., superlattices), quantitative
      analysis is hindered by mathematical difficulties inherent in a time-dependent,
      free-boundary Navier-Stokes problem. More tractable low viscosity approximations
      are available, but these do not necessarily capture the moderate viscosity regime
      of the most interesting experiments. Here we focus on weakly nonlinear behavior
      and compare the scaling results derived from symmetry arguments in the low
      viscosity limit with the computed coefficients of appropriate amplitude equations
      using both the full Navier-Stokes equations and a reduced set of partial
      differential equations due to Zhang and Vinals. We find the range of viscosities
      over which one can expect "low viscosity" theories to hold. We also find that
      there is an optimal viscosity range for locating superlattice patterns
      experimentally-large enough that the region of parameters giving stable patterns
      is not impracticably small, yet not so large that crucial resonance effects are
      washed out. These results help explain some of the discrepancies between theory
      and experiment.

PMID- 21867276
TI  - Effects of nonresonant interaction in ensembles of phase oscillators.
AB  - We consider general properties of groups of interacting oscillators, for which
      the natural frequencies are not in resonance. Such groups interact via
      nonoscillating collective variables like the amplitudes of the order parameters
      defined for each group. We treat the phase dynamics of the groups using the Ott
      Antonsen ansatz and reduce it to a system of coupled equations for the order
      parameters. We describe different regimes of cosynchrony in the groups. For a
      large number of groups, heteroclinic cycles, corresponding to a sequential
      synchronous activity of groups and chaotic states where the order parameters
      oscillate irregularly, are possible.

PMID- 21867277
TI  - Construction of traveling clusters in the Hamiltonian mean-field model by
      nonequilibrium statistical mechanics and Bernstein-Greene-Kruskal waves.
AB  - Traveling clusters are ubiquitously observed in the Hamiltonian mean-field model
      for a wide class of initial states, which are not predicted to become spatially
      inhomogeneous states by nonequilibrium statistical mechanics and by nonlinear
      Landau damping. To predict such a cluster state from a given initial state, we
      combine nonequilibrium statistical mechanics and a construction method of
      Bernstein-Greene-Kruskal (BGK) waves with the aid of phenomenological
      assumptions. The phenomenological theory is partially successful, and the
      theoretically constructed cluster states are in good agreement with N-body
      simulations. Robustness of the theory is also discussed for unsuccessful initial
      states.

PMID- 21867278
TI  - Homoclinic orbits and chaos in a pair of parametrically driven coupled nonlinear
      resonators.
AB  - We study the dynamics of a pair of parametrically driven coupled nonlinear
      mechanical resonators of the kind that is typically encountered in applications
      involving microelectromechanical systems (MEMS) and nanoelectromechanical systems
      (NEMS). We take advantage of the weak damping that characterizes these systems to
      perform a multiple-scales analysis and obtain amplitude equations, describing the
      slow dynamics of the system. This picture allows us to expose the existence of
      homoclinic orbits in the dynamics of the integrable part of the slow equations of
      motion. Using a version of the high-dimensional Melnikov approach, developed by
      G. Kovacic and S. Wiggins [Physica D 57, 185 (1992)], we are able to obtain
      explicit parameter values for which these orbits persist in the full system,
      consisting of both Hamiltonian and non-Hamiltonian perturbations, to form so
      called Silnikov orbits, indicating a loss of integrability and the existence of
      chaos. Our analytical calculations of Silnikov orbits are confirmed numerically.

PMID- 21867279
TI  - Isochronal chaos synchronization of delay-coupled optoelectronic oscillators.
AB  - We study experimentally chaos synchronization of nonlinear optoelectronic
      oscillators with time-delayed mutual coupling and self-feedback. Coupling three
      oscillators in a chain, we find that the outer two oscillators always
      synchronize. In contrast, isochronal synchronization of the mediating middle
      oscillator is found only when self-feedback is added to the middle oscillator. We
      show how the stability of the isochronal solution of any network, including the
      case of three coupled oscillators, can be determined by measuring the
      synchronization threshold of two unidirectionally coupled systems. In addition,
      we provide a sufficient condition that guarantees global asymptotic stability of
      the synchronized solution.

PMID- 21867280
TI  - Towards easier realization of time-delayed feedback control of odd-number orbits.
AB  - We develop generalized time-delayed feedback schemes for the stabilization of
      periodic orbits with an odd number of positive Floquet exponents, which are
      particularly well suited for experimental realization. We construct the parameter
      regimes of successful control and validate these by numerical simulations and
      numerical continuation methods. In particular, it is shown how periodic orbits
      can be stabilized with symmetric feedback matrices by introducing an additional
      latency time in the control loop. Finally, we show using normal form analysis and
      numerical simulations how our results could be implemented in a laser setup using
      optoelectronic feedback.

PMID- 21867281
TI  - Strong-coupling limit in heterogeneous populations of coupled oscillators.
AB  - Coupled oscillators can be heterogeneous in the sense that parameter values of
      constituent oscillators are not uniform for various reasons. Here it is discussed
      how such a system behaves in the strong-coupling limit. A theory is developed
      under certain assumptions and then used to quite generally explain an empirical
      law about a phase transition boundary in a class of heterogeneous populations of
      coupled oscillators such that bifurcation parameters are distributed. Results
      obtained here will be useful as a starting point for studying the behavior of
      such systems for moderate coupling strengths.

PMID- 21867282
TI  - Global structure of periodicity hubs in Lyapunov phase diagrams of dissipative
      flows.
AB  - Infinite cascades of periodicity hubs were predicted and very recently observed
      experimentally to organize stable oscillations of some dissipative flows. Here we
      describe the global mechanism underlying the genesis and organization of networks
      of periodicity hubs in control parameter space of a simple prototypical flow,
      namely a Rossler's oscillator. We show that spirals associated with periodicity
      hubs emerge and accumulate at the folding of certain fractal-like sheaves of
      Shilnikov homoclinic bifurcations of a common saddle-focus equilibrium. The
      specific organization of hub networks is found to depend strongly on the
      interaction between the homoclinic orbits and the global structure of the
      underlying attractor.

PMID- 21867283
TI  - Escape of quantum particles from an open cavity.
AB  - A negative ion irradiated by a laser provides a coherent source of electrons
      propagating out from the location of the negative ion. The total escape rates of
      the electrons when the negative ion is placed inside an open cavity in the shape
      of a wedge are studied. It is shown that the wedge induces significant
      oscillations in the total escape rates because of quantum interference effects.
      In particular, it is shown that, for a wedge with an opening angle of pi/N, where
      N is an arbitrary positive integer, there are (2N-1) induced oscillations in the
      rates. As a demonstration, the case for a wedge with an opening angle pi/5 is
      calculated and analyzed in detail.

PMID- 21867284
TI  - Kolmogorov-Sinai entropy of many-body Hamiltonian systems.
AB  - The Kolmogorov-Sinai (KS) entropy is a central measure of complexity and chaos.
      Its calculation for many-body systems is an interesting and important challenge.
      In this paper, the evaluation is formulated by considering N-dimensional
      symplectic maps and deriving a transfer matrix formalism for the stability
      problem. This approach makes explicit a duality relation that is exactly
      analogous to one found in a generalized Anderson tight-binding model and leads to
      a formally exact expression for the finite-time KS entropy. Within this formalism
      there is a hierarchy of approximations, the final one being a diagonal
      approximation that only makes use of instantaneous Hessians of the potential to
      find the KS entropy. By way of a nontrivial illustration, the KS entropy of N
      identically coupled kicked rotors (standard maps) is investigated. The validity
      of the various approximations with kicking strength, particle number, and time
      are elucidated. An analytic formula for the KS entropy within the diagonal
      approximation is derived and its range of validity is also explored.

PMID- 21867285
TI  - Pattern formation in a thread falling onto a moving belt: an "elastic sewing
      machine".
AB  - We study the dynamics of instability and pattern formation in a slender elastic
      thread that is continuously fed onto a surface moving at constant speed V in its
      own plane. As V is decreased below a critical value V(c), the steady "dragged
      catenary" configuration of the thread becomes unstable to sinusoidal meanders and
      thence to a variety of more complex patterns including biperiodic meanders,
      figures of 8, "W," "two-by-one," and "two-by-two" patterns, and double coiling.
      Laboratory experiments are performed to determine the phase diagram of these
      patterns as a function of V, the thread feeding speed U, and the fall height H.
      The meandering state is quantified by measuring its amplitude and frequency as
      functions of V, which are consistent with a Hopf bifurcation. We formulate a
      numerical model for a slender elastic thread that predicts well the observed
      steady shapes but fails to predict the frequency of the onset of meandering,
      probably because of slippage of the thread relative to the belt. A comparison of
      our phase diagram with the analogous diagram for a thread of viscous fluid
      falling on a moving surface reveals many similarities, but each contains several
      patterns that are not found in the other.

PMID- 21867286
TI  - Decoherence, entanglement decay, and equilibration produced by chaotic
      environments.
AB  - We investigate decoherence in quantum systems coupled via dephasing-type
      interactions to an arbitrary environment with chaotic underlying classical
      dynamics. The coherences of the reduced state of the central system written in
      the preferential energy eigenbasis are quantum Loschmidt echoes, which in the
      strong coupling regime are characterized at long time scales by fluctuations
      around a constant mean value. We show that due to the chaotic dynamics of the
      environment, the mean value and the width of the Loschmidt-echo fluctuations are
      inversely proportional to the quantity we define as the effective Hilbert-space
      dimension of the environment, which in general is smaller than the dimension of
      the entire available Hilbert space. Nevertheless, in the semiclassical regime
      this effective Hilbert-space dimension is in general large, in which case even a
      chaotic environment with few degrees of freedom produces decoherence without
      revivals. Moreover we show that in this regime the environment leads the central
      system to equilibrate to the time average of its reduced density matrix, which
      corresponds to a diagonal state in the preferential energy eigenbasis. For the
      case of two uncoupled, initially entangled central systems that interact with
      identical local quantum environments with chaotic underlying classical dynamics,
      we show that in the semiclassical limit the equilibration state is arbitrarily
      close to a separable state. We confirm our results with numerical simulations in
      which the environment is modeled by the quantum kicked rotor in the chaotic
      regime.

PMID- 21867287
TI  - Double-slit experiments with microwave billiards.
AB  - Single and double-slit experiments are performed with two microwave billiards
      with the shapes of a rectangle and a quarter stadium, respectively. The classical
      dynamics of the former is regular, whereas that of the latter is chaotic.
      Microwaves can leave the billiards via slits in the boundary, forming
      interference patterns on a screen. The aim is to determine the effect of the
      billiard dynamics on their structure. For this the development of a method for
      the construction of a directed wave packet by means of an array of multiple
      antennas was crucial. The interference patterns show a sensitive dependence not
      only on the billiard dynamics but also on the initial position and direction of
      the wave packet.

PMID- 21867288
TI  - Control of the Hopf-Turing transition by time-delayed global feedback in a
      reaction-diffusion system.
AB  - Application of time-delayed feedback is a practical method of controlling
      bifurcations in reaction-diffusion systems. It has been shown that for a suitable
      feedback strength, time delay beyond a threshold may induce spatiotemporal
      instabilities. For an appropriate parameter space with differential diffusivities
      of the activator-inhibitor species, delayed feedback may generate Turing
      instability via a Hopf-Turing transition, resulting in stationary patterns. This
      is explored by a theoretical scheme in a photosensitive chlorine dioxide-iodine
      malonic acid reaction-diffusion system where the delayed feedback is externally
      tuned by photoillumination intensity. Our analytical results corroborate with
      direct numerical simulations.

PMID- 21867289
TI  - Optimal reconstruction of dynamical systems: a noise amplification approach.
AB  - In this work we propose an objective function to guide the search for a state
      space reconstruction of a dynamical system from a time series of measurements.
      These statistics can be evaluated on any reconstructed attractor, thereby
      allowing a direct comparison among different approaches: (uniform or nonuniform)
      delay vectors, PCA, Legendre coordinates, etc. It can also be used to select the
      most appropriate parameters of a reconstruction strategy. In the case of delay
      coordinates this translates into finding the optimal delay time and embedding
      dimension from the absolute minimum of the advocated cost function. Its
      definition is based on theoretical arguments on noise amplification, the
      complexity of the reconstructed attractor, and a direct measure of local stretch
      which constitutes an irrelevance measure. The proposed method is demonstrated on
      synthetic and experimental time series.

PMID- 21867290
TI  - Criticality and long-range correlations in time series in classical and quantum
      systems.
AB  - We present arguments which indicate that a transitional state in between two
      different regimes implies the occurrence of 1/f time series and that this
      property is generic in both classical and quantum systems. Our study focuses on
      two particular examples: the one-dimensional module-1 logistic map and nuclear
      excitation spectra obtained with a schematic shell-model Hamiltonian. We suggest
      that a transitional point is characterized by the long-range correlations implied
      by 1/f time series. We apply a Fourier spectral analysis and the detrended
      fluctuation analysis method to study the fluctuations to each system.

PMID- 21867291
TI  - Classical dynamics of a two-species condensate driven by a quantum field.
AB  - We present a stability analysis of an interacting two-species Bose-Einstein
      condensate driven by a quantized field in the semiclassical limit. Transitions
      from Rabi to Josephson dynamics are identified depending on both the interatomic
      interaction to field-condensate coupling ratio and the ratio between the total
      excitation number and the condensate size. The quantized field is found to
      produce asymmetric dynamics for symmetric initial conditions for both Rabi and
      Josephson oscillations.

PMID- 21867292
TI  - Phase-flip transition in relay-coupled nonlinear oscillators.
AB  - We study the dynamics of oscillators that are coupled in relay; namely, through
      an intermediary oscillator. From previous studies it is known that the
      oscillators show a transition from in-phase to out-of-phase oscillations or vice
      versa when the interactions involve a time delay. Here we show that, in the
      absence of time delay, relay coupling through conjugate variables has the same
      effect. However, this phase-flip transition does not occur abruptly at a certain
      critical value of the coupling parameter. Instead we find a parameter region
      around the phase-flip transition where bistability occurs. In this parameter
      interval in-phase and out-of-phase oscillations coexist with changing sizes of
      their basins of attraction. Further increase of the coupling strength leads to
      amplitude death and subsequently to the stabilization of a fixed point. These
      transitions are characterized through various quantities such as the average
      phase difference and crossings in the spectrum of Lyapunov exponents. Numerical
      results are presented for a specific case of coupled Rossler-like oscillators.

PMID- 21867293
TI  - Stability of a chain of phase oscillators.
AB  - We study a chain of N+1 phase oscillators with asymmetric but uniform coupling.
      This type of chain possesses 2(N) ways to synchronize in so-called traveling wave
      states, i.e., states where the phases of the single oscillators are in relative
      equilibrium. We show that the number of unstable dimensions of a traveling wave
      equals the number of oscillators with relative phase close to pi. This implies
      that only the relative equilibrium corresponding to approximate in-phase
      synchronization is locally stable. Despite the presence of a Lyapunov-type
      functional, periodic or chaotic phase slipping occurs. For chains of lengths 3
      and 4 we locate the region in parameter space where rotations (corresponding to
      phase slipping) are present.

PMID- 21867294
TI  - Hyperbolic chaotic attractor in amplitude dynamics of coupled self-oscillators
      with periodic parameter modulation.
AB  - The paper proposes an approach to constructing feasible examples of dynamical
      systems with hyperbolic chaotic attractors based on the successive transfer of
      excitation between two pairs of self-oscillators that are alternately active. An
      angular variable that measures the relations of the current amplitudes for the
      two oscillators of each pair undergoes a transformation in accordance with the
      expanding circle map during each cycle of the process. We start with equations
      describing the dynamics in terms of complex or real amplitudes and then examine
      two models based on van der Pol oscillators. One model corresponds to the
      situation of equality of natural frequencies of the partial oscillators, and
      another to a nonresonant ratio of the oscillation frequencies relating to each of
      the two pairs. Dynamics of all models are illustrated with diagrams indicating
      the transformation of the angular variables, portraits of attractors, Lyapunov
      exponents, etc. The uniformly hyperbolic nature of the attractor in the
      stroboscopic Poincare map is confirmed for a real-amplitude version of the
      equations by computations of statistical distribution of angles between stable
      and unstable manifolds at a representative set of points on the attractor. In
      other versions of the equations the attractors relate presumably to the partially
      hyperbolic class.

PMID- 21867295
TI  - Optimal phase response curves for stochastic synchronization of limit-cycle
      oscillators by common Poisson noise.
AB  - We consider optimization of phase response curves for stochastic synchronization
      of noninteracting limit-cycle oscillators by common Poisson impulsive signals.
      The optimal functional shape for sufficiently weak signals is sinusoidal, but can
      differ for stronger signals. By solving the Euler-Lagrange equation associated
      with the minimization of the Lyapunov exponent characterizing synchronization
      efficiency, the optimal phase response curve is obtained. We show that the
      optimal shape mutates from a sinusoid to a sawtooth as the constraint on its
      squared amplitude is varied.

PMID- 21867296
TI  - Quantum chaos in one dimension?
AB  - In this work we investigate the inverse of the celebrated Bohigas-Giannoni-Schmit
      conjecture. Using two inversion methods we compute a one-dimensional potential
      whose lowest N eigenvalues obey random matrix statistics. Our numerical results
      indicate that in the asymptotic limit N->infinity the solution is nowhere
      differentiable and most probably nowhere continuous. Thus such a counterexample
      does not exist.

PMID- 21867297
TI  - Emergent multistability and frustration in phase-repulsive networks of
      oscillators.
AB  - The collective dynamics of oscillator networks with phase-repulsive coupling is
      studied, considering various network sizes and topologies. The notion of link
      frustration is introduced to characterize and quantify the network dynamical
      states. In opposition to widely studied phase-attractive case, the properties of
      final dynamical states in our model critically depend on the network topology. In
      particular, each network's total frustration value is intimately related to its
      topology. Moreover, phase-repulsive networks in general display multiple final
      frustration states, whose statistical and stability properties are uniquely
      identifying them.

PMID- 21867298
TI  - Resonance phenomenon for the Galerkin-truncated Burgers and Euler equations.
AB  - It is shown that the solutions of inviscid hydrodynamical equations with
      suppression of all spatial Fourier modes having wave numbers in excess of a
      threshold K(G) exhibit unexpected features. The study is carried out for both the
      one-dimensional Burgers equation and the two-dimensional incompressible Euler
      equation. For large K(G) and smooth initial conditions, the first symptom of
      truncation, a localized short-wavelength oscillation which we call a "tyger," is
      caused by a resonant interaction between fluid particle motion and truncation
      waves generated by small-scale features (shocks, layers with strong vorticity
      gradients, etc.). These tygers appear when complex-space singularities come
      within one Galerkin wavelength lambda(G)=2pi/K(G) from the real domain and
      typically arise far away from preexisting small-scale structures at locations
      whose velocities match that of such structures. Tygers are weak and strongly
      localized at first-in the Burgers case at the time of appearance of the first
      shock their amplitudes and widths are proportional to K(G)(-2/3) and K(G)(-1/3),
      respectively-but grow and eventually invade the whole flow. They are thus the
      first manifestations of the thermalization predicted by T. D. Lee [Q. J. Appl.
      Math. 10, 69 (1952)]. The sudden dissipative anomaly-the presence of a finite
      dissipation in the limit of vanishing viscosity after a finite time t(?)-which is
      well known for the Burgers equation and sometimes conjectured for the three
      dimensional Euler equation, has as counterpart, in the truncated case, the
      ability of tygers to store a finite amount of energy in the limit K(G)->infinity.
      This leads to Reynolds stresses acting on scales larger than the Galerkin
      wavelength and thus prevents the flow from converging to the inviscid-limit
      solution. There are indications that it may eventually be possible to purge the
      tygers and thereby to recover the correct inviscid-limit behavior.

PMID- 21867299
TI  - Hybrid free-surface flows in a two-dimensional channel.
AB  - Hybrid free-surface flows past disturbances in a two-dimensional channel are
      identified and studied. The fluid is assumed to be inviscid and incompressible,
      and the flow to be steady and irrotational. The disturbances consist of a step in
      the bottom of the channel and a flat object lying on the free-surface (e.g., a
      sluice gate). A weakly nonlinear one-dimensional analysis is used to classify the
      possible types of solutions, and nonlinear solutions are obtained numerically by
      a boundary integral equation method.

PMID- 21867300
TI  - Weakly nonlinear study of normal-field instability in confined ferrofluids.
AB  - Similar to the classic three-dimensional Rosensweig instability, a ferrofluid
      confined in a vertical Hele-Shaw cell subjected to an in-plane normal magnetic
      field develops a periodic array of peaked interfacial structures. We perform a
      weakly nonlinear analysis that is able to reproduce the morphology of such
      pattern formation phenomenon at lowest nonlinear order. A mode-coupling theory is
      applied to compare the early nonlinear evolution of the interface with static
      shapes obtained when relevant forces equilibrate. Our nonlinear results indicate
      that the time-evolving shapes tend to approach stable stationary solutions.

PMID- 21867301
TI  - Momentum and mass fluxes in a gas confined between periodically structured
      surfaces at different temperatures.
AB  - It is well known that in a gas-filled duct or channel along which a temperature
      gradient is applied, a thermal creep flow is created. Here we show that a mass
      and momentum flux can also be induced in a gas confined between two parallel
      structured surfaces at different temperatures, i.e., orthogonal to the
      temperature gradient. We use both analytical and numerical methods to compute the
      resulting fluxes. The momentum flux assumes its maximum value in the free
      molecular flow regime, the (normalized) mass flux in the transition flow regime.
      The discovered phenomena could find applications in methods for energy-conversion
      and thermal pumping of gases.

PMID- 21867302
TI  - Second-order closure in stratified turbulence: simulations and modeling of bulk
      and entrainment regions.
AB  - The parametrization of small-scale turbulent fluctuations in convective systems
      and in the presence of strong stratification is a key issue for many applied
      problems in oceanography, atmospheric science, and planetology. In the presence
      of stratification, one needs to cope with bulk turbulent fluctuations and with
      inversion regions, where temperature, density, or both develop highly nonlinear
      mean profiles due to the interactions between the turbulent boundary layer and
      the unmixed-stable-flow above or below it. We present a second-order closure able
      to cope simultaneously with both bulk and boundary layer regions, and we test it
      against high-resolution state-of-the-art two-dimensional numerical simulations in
      a convective and stratified belt for values of the Rayleigh number up to
      Ra~10(10). Data are taken from a Rayleigh-Taylor system confined by the existence
      of an adiabatic gradient.

PMID- 21867303
TI  - Nonlinear oscillatory convective regimes in a three-layer system with an inclined
      temperature gradient.
AB  - The influence of the horizontal component of the temperature gradient on
      nonlinear regimes of oscillatory convection developed under the joint action of
      buoyant and thermocapillary effects in a multilayer system is investigated. Two
      dimensional convective regimes are studied by the finite difference method. Rigid
      heat-insulated lateral walls are considered. It is found that the region of
      nonlinear asymmetric oscillations is restricted by the Grashof number values,
      both from below and from above, by the steady states.

PMID- 21867304
TI  - Zig-zag arrangement of four electrodes for ac electro-osmotic micropumps.
AB  - This paper deals with the mathematical modeling of traveling-wave ac electro
      osmotic micropumps with a zig-zag arrangement of microelectrodes. A mathematical
      model based on the Poisson-Nernst-Planck-Navier-Stokes description is used in
      this study within the physically relevant ranges of the model parameters. We
      present an extensive set of parametrical studies concerning the dependence of the
      net velocity on a variety of parameters. We also demonstrate limits of the
      validity of the commonly used Capacitor-Resistor-Capacitor model. In order to
      achieve high net velocities, we found that there are the optimal values of the
      electrode length, the shift between the top and bottom electrode arrays, and the
      signal frequency. Performance of the zig-zag micropumps is evaluated by the means
      of back-pressure loads. The suggested zig-zag design brings two main benefits:
      (i) it allows an easier construction of four-phase traveling-wave micropumps
      without the need of spatially complicated electrode connections, and (ii) the zig
      zag pumps can provide higher flow rates than those with single-sided coplanar
      arrangements. Another robust feature of the proposed zig-zag system is that a
      single flow reversal is observed at the ac frequency approximately six times
      higher than the reciprocal resistor-capacitor time even in low-amplitude regimes.

PMID- 21867305
TI  - Logarithmic nonlinear Schrodinger equation and irrotational, compressible flows:
      an exact solution.
AB  - A class of irrotational, isentropic, and compressible flows is studied
      theoretically by formulating the density and the velocity potential in a Madelung
      transformation. The resulting nonlinear Schrodinger equation is solved in terms
      of similarity variables. One particular family of exact solutions, valid for any
      ratio of the specific heat capacities of the gas, permits explicit expressions of
      the fluid properties and velocities in terms of time and spatial coordinates.
      Analytically, the density is a Gaussian function of the similarity variable,
      while the temperature is a function of time only. This method is applicable in
      one (1D), two, and three dimensional geometries. As a simple example, a 1D gas
      column, with mass injection on one side and a steadily translating wall on the
      other, can be formulated exactly. The connection with the evolution of an
      unsteady velocity potential will also be examined.

PMID- 21867306
TI  - Simplifying the complexity of pipe flow.
AB  - Transitional pipe flow is modeled as a one-dimensional excitable and bistable
      medium. Models are presented in two variables, turbulence intensity and mean
      shear, that evolve according to established properties of transitional
      turbulence. A continuous model captures the essence of the puff-slug transition
      as a change from excitability to bistability. A discrete model, which
      additionally incorporates turbulence locally as a chaotic repeller, reproduces
      almost all large-scale features of transitional pipe flow. In particular, it
      captures metastable localized puffs, puff splitting, slugs, localized edge
      states, a continuous transition to sustained turbulence via spatiotemporal
      intermittency (directed percolation), and a subsequent increase in turbulence
      fraction toward uniform, featureless turbulence.

PMID- 21867307
TI  - Flow-induced channel formation in the cytoplasm of motile cells.
AB  - A model is presented to explain the development of flow channels within the
      cytoplasm of the plasmodium of the giant amoeba Physarum polycephalum. The
      formation of channels is related to the development of a self-organizing tubular
      network in large cells. Experiments indicate that the flow of cytoplasm is
      involved in the development and organization of these networks, and the
      mathematical model proposed here is motivated by recent experiments involving the
      observation of development of flow channel in small cells. A model of pressure
      driven flow through a polymer network is presented in which the rate of flow
      increases the rate of depolymerization. Numerical solutions and asymptotic
      analysis of the model in one spatial dimension show that under very general
      assumptions this model predicts the formation of channels in response to flow.

PMID- 21867308
TI  - Local temperature measurements in turbulent rotating Rayleigh-Benard convection.
AB  - We present local temperature measurements of turbulent Rayleigh-Benard convection
      with rotation about a vertical axis. The fluid, water with Prandtl number about
      6, was confined in a cell with a square cross section of 7.3*7.3 cm(2) and a
      height of 9.4 cm. Temperature fluctuations and boundary-layer profiles were
      measured for Rayleigh numbers 1*10(7)<Ra<5*10(8) and Taylor numbers 0<Ta<5*10(9).
      We present statistics of the temperature field measured by a single thermistor
      located along the vertical centerline of the cell or by an array of thermistors
      distributed laterally from that centerline. The statistics include the mean
      temperature, standard deviation, skewness, and the probability distribution
      functions at various locations in the cell, especially near and inside the
      thermal boundary layer. The effects of rotation on these quantities are discussed
      including the presence of a rotation-dependent mean vertical temperature
      gradient, the negative skewness of temperature fluctuations in the boundary
      layer, and the horizontal homogenization of temperature.

PMID- 21867309
TI  - Influence of liquid density on the parametric shape instability of
      sonoluminescence bubbles in water and sulfuric acid.
AB  - Parametric shape instability of sonoluminescing argon bubbles in water and
      aqueous H(2)SO(4) was numerically analyzed considering gas and liquid density
      variations. The employed model couples Gilmore, Tait (liquid) and van der Waals
      (gas) equations to simulate radial dynamics and density changes, respectively.
      Shape stability-instability zones in the P(a)-R(0) space resulted from a linear
      stability analysis. For the argon-water and argon-water-acid systems, numerical
      results indicate a rapid rise in both gas and liquid densities during final
      stages of bubble implosion which result in a stabilizing effect on the parametric
      instability.

PMID- 21867310
TI  - Prediction of fluid velocity slip at solid surfaces.
AB  - The observed flow enhancement in highly confining geometries is believed to be
      caused by fluid velocity slip at the solid wall surface. Here we present a simple
      and highly accurate method to predict this slip using equilibrium molecular
      dynamics. Unlike previous equilibrium molecular dynamics methods, it allows us to
      directly compute the intrinsic wall-fluid friction coefficient rather than an
      empirical friction coefficient that includes all sources of friction for planar
      shear flow. The slip length predicted by our method is in excellent agreement
      with the slip length obtained from direct nonequilibrium molecular dynamics
      simulations.

PMID- 21867311
TI  - High Reynolds number magnetohydrodynamic turbulence using a Lagrangian model.
AB  - With the help of a model of magnetohydrodynamic (MHD) turbulence tested
      previously, we explore high Reynolds number regimes up to equivalent resolutions
      of 6000(3) grid points in the absence of forcing and with no imposed uniform
      magnetic field. For the given initial condition chosen here, with equal kinetic
      and magnetic energy, the flow ends up being dominated by the magnetic field, and
      the dynamics leads to an isotropic Iroshnikov-Kraichnan energy spectrum. However,
      the locally anisotropic magnetic field fluctuations perpendicular to the local
      mean field follow a Kolmogorov law. We find that the ratio of the eddy turnover
      time to the Alfven time increases with wave number, contrary to the so-called
      critical balance hypothesis. Residual energy and helicity spectra are also
      considered; the role played by the conservation of magnetic helicity is studied,
      and scaling laws are found for the magnetic helicity and residual helicity
      spectra. We put these results in the context of the dynamics of a globally
      isotropic MHD flow that is locally anisotropic because of the influence of the
      strong large-scale magnetic field, leading to a partial equilibration between
      kinetic and magnetic modes for the energy and the helicity.

PMID- 21867312
TI  - Wrinkled flames and geometrical stretch.
AB  - Localized wrinkles of thin premixed flames subject to hydrodynamic instability
      and geometrical stretch of uniform intensity (S) are studied. A stretch-affected
      nonlinear and nonlocal equation, derived from an inhomogeneous Michelson
      Sivashinsky equation, is used as a starting point, and pole decompositions are
      used as a tool. Analytical and numerical descriptions of isolated (centered or
      multicrested) wrinkles with steady shapes (in a frame) and various amplitudes are
      provided; their number increases rapidly with 1/S>0. A large constant S>0 weakens
      or suppresses all localized wrinkles (the larger the wrinkles, the easier the
      suppression), whereas S<0 strengthens them; oscillations of S further restrict
      their existence domain. Self-similar evolutions of unstable many-crested patterns
      are obtained. A link between stretch, nonlinearity, and instability with the
      cutoff size of the wrinkles in turbulent flames is suggested. Open problems are
      evoked.

PMID- 21867313
TI  - Two-phase flow in a rough fracture: experiment and modeling.
AB  - To develop and test theory-based procedures for modeling two-phase flow through
      fractures, it is important to be able to compare computational results for a
      fracture with experiments performed on the exact same fracture. Unfortunately for
      real fractures, any attempt to image the fracture and to produce a numerical
      model of the fracture accessible to computer modeling unavoidably results in a
      coarsening of the resolution, with the very small-scale features of the imaged
      fracture averaged to produce the numerical representation used in modeling.
      Contrary to the hope that these high-resolution features would be unimportant,
      several modeling efforts have shown that such changes in resolution do affect the
      flow. Therefore, the numerical representation is different from the real fracture
      because of this unavoidable coarsening of the resolution. To remove the problems
      caused by the use of different fractures in the experiment and in the model, the
      fracture used in our experiments was stereographically constructed from the same
      numerical representation used in the modeling so that the only difference between
      the experimental "fracture" and the modeling "fracture" is a manufacturing error
      of approximately 3% or less in the aperture sizes of the manufactured
      experimental model. Using several models not unlike others in the literature, we
      modeled injection of air into the water-saturated fracture. The modeling results
      are compared to experimental results for injection of air into the water
      saturated stereolithographically constructed fracture. A comparison between
      modeling and experimental results for the essentially identical fractures shows a
      much better detailed agreement than obtained in other studies, which compared
      experimental flows on the real fracture with modeling results for a lower
      resolution representation of the real fracture. This suggests that many of the
      differences between experiment and modeling in previous work resulted from the
      differences between the experimental and modeling fractures. For our low
      capillary-number cases, the best agreement with experiment is for a modification
      of invasion percolation with trapping (IPwt) that included approximations to
      viscosity ratio effects and to the interfacial tension effects in reducing very
      short-range curvature.

PMID- 21867314
TI  - Nonlinear dynamo action in a precessing cylindrical container.
AB  - It is numerically demonstrated by means of a magnetohydrodynamics code that
      precession can trigger the dynamo effect in a cylindrical container. When the
      Reynolds number, based on the radius of the cylinder and its angular velocity,
      increases, the flow, which is initially centrosymmetric, loses its stability and
      bifurcates to a quasiperiodic motion. This unsteady and asymmetric flow is shown
      to be capable of sustaining dynamo action in the linear and nonlinear regimes.
      The magnetic field thus generated is unsteady and quadrupolar. These numerical
      evidences of dynamo action in a precessing cylindrical container may be useful
      for an experiment now planned at the Dresden sodium facility for dynamo and
      thermohydraulic studies in Germany.

PMID- 21867315
TI  - Crossover between Rayleigh-Taylor instability and turbulent cascading atomization
      mechanism in the bag-breakup regime.
AB  - The question of whether liquid atomization depends on instability dynamics
      (through refinements of Rayleigh-Plateau, Rayleigh-Taylor, or Kelvin-Helmholtz
      mechanisms) or on turbulent cascades, as suggested by Richardson and Kolmogorov,
      is still open. In this paper, experimental results reveal that both mechanisms
      are needed to explain the probability density functions (PDFs) of the droplets in
      a spray obtained from an industrial fan spray nozzle. Instability of Rayleigh
      Taylor type controls the size of the largest droplets while the smallest droplets
      follow a PDF given by a turbulent cascading mechanism characterized by a log-Levy
      stable law that has a stability parameter equal to 1.70. This value is very close
      to the inverse value of the Flory exponent and can be related to a recent model
      developed by N. Rimbert for intermittency modeling stemming from self-avoiding
      random vortex stretching.

PMID- 21867316
TI  - Diffusion in Coulomb crystals.
AB  - Diffusion in Coulomb crystals can be important for the structure of neutron star
      crusts. We determine diffusion constants D from molecular dynamics simulations.
      We find that D for Coulomb crystals with relatively soft-core 1/r interactions
      may be larger than D for Lennard-Jones or other solids with harder-core
      interactions. Diffusion, for simulations of nearly perfect body-centered-cubic
      lattices, involves the exchange of ions in ringlike configurations. Here ions
      "hop" in unison without the formation of long lived vacancies. Diffusion, for
      imperfect crystals, involves the motion of defects. Finally, we find that
      diffusion, for an amorphous system rapidly quenched from Coulomb parameter
      Gamma=175 to Coulomb parameters up to Gamma=1750, is fast enough that the system
      starts to crystalize during long simulation runs. These results strongly suggest
      that Coulomb solids in cold white dwarf stars, and the crust of neutron stars,
      will be crystalline and not amorphous.

PMID- 21867317
TI  - Effect of the plasma-generated magnetic field on relativistic electron transport.
AB  - In the fast-ignition scheme, relativistic electrons transport energy from the
      laser deposition zone to the dense part of the target where the fusion reactions
      can be ignited. The magnetic fields and electron collisions play an important
      role in the collimation or defocusing of this electron beam. Detailed description
      of these effects requires large-scale kinetic calculations and is limited to
      short time intervals. In this paper, a reduced kinetic model of fast electron
      transport coupled to the radiation hydrodynamic code is presented. It opens the
      possibility to carry on hybrid simulations in a time scale of tens of picoseconds
      or more. It is shown with this code that plasma-generated magnetic fields induced
      by noncollinear temperature and density gradients may strongly modify electron
      transport in a time scale of a few picoseconds. These fields tend to defocus the
      electron beam, reducing the coupling efficiency to the target. This effect, that
      was not seen before in shorter time simulations, has to be accounted for in any
      ignition design using electrons as a driver.

PMID- 21867319
TI  - Static and dynamic shear viscosity of a single-layer complex plasma.
AB  - The static and dynamic (complex) shear viscosity of a single-layer dusty plasma
      is measured by applying, respectively, a stationary and a periodically modulated
      shear stress, induced by the light pressure of manipulating laser beams. Under
      static conditions we observe a decrease of the viscosity with increasing shear
      rate, the so-called shear-thinning behavior. Under oscillating shear both the
      magnitude and the ratio of the dissipative and elastic contributions to the
      complex viscosity show strong frequency dependence, as the system changes from
      viscous to elastic in nature with increasing excitation frequency. Accompanying
      molecular dynamics simulations explain and support the experimental observations.

PMID- 21867318
TI  - Observation of turbulence suppression after electron-cyclotron-resonance-heating
      switch-off on the HL-2A tokamak.
AB  - The formation of a transient internal transport barrier (ITB) is observed after
      the electron-cyclotron-resonance-heating (ECRH) switch-off in the HL-2A plasmas,
      characterized by transient increase of central electron temperature. The newly
      developed correlation reflectometer provided direct measurements showing
      reduction of turbulence in the region of steepened gradients for the period of
      ITB formation triggered by the ECRH switch-off. Furthermore, the reduction of
      core turbulence is correlated in time with the appearance of a low-frequency mode
      with a spectrally broad poloidal structure that peaks near zero frequency in the
      core region. These structures have low poloidal mode number, high poloidal
      correlation, and short radial correlation and are strongly coupled with high
      frequency ambient turbulence. Observation indicates that these structures play
      important roles in the reduction of the core turbulence and in improvements of
      the core transport after the off-axis ECRH is turned off.

PMID- 21867320
TI  - Chain of coupled van der Pol oscillators as model system for density waves in
      dusty plasmas.
AB  - Recent investigations of dust-density waves in a dusty plasma under microgravity
      conditions [K. O. Menzel et al., Phys. Rev. Lett. 104, 235002 (2010)] showed that
      the wave field consists of distinct regions of different frequencies. These so
      called frequency clusters are known from simulations of chains of mutually
      coupled van der Pol oscillators. The behavior of distinct oscillators adjacent to
      the cluster boundaries were studied numerically. The interaction of these
      oscillators leads to periodic frequency pulling, a typical feature of driven van
      der Pol oscillators that is also observed in our experiments.

PMID- 21867321
TI  - Decay of helical and nonhelical magnetic knots.
AB  - We present calculations of the relaxation of magnetic field structures that have
      the shape of particular knots and links. A set of helical magnetic flux
      configurations is considered, which we call n-foil knots of which the trefoil
      knot is the most primitive member. We also consider two nonhelical knots; namely,
      the Borromean rings as well as a single interlocked flux rope that also serves as
      the logo of the Inter-University Centre for Astronomy and Astrophysics in Pune,
      India. The field decay characteristics of both configurations is investigated and
      compared with previous calculations of helical and nonhelical triple-ring
      configurations. Unlike earlier nonhelical configurations, the present ones cannot
      trivially be reduced via flux annihilation to a single ring. For the n-foil knots
      the decay is described by power laws that range form t(-2/3) to t(-1/3), which
      can be as slow as the t(-1/3) behavior for helical triple-ring structures that
      were seen in earlier work. The two nonhelical configurations decay like t(-1),
      which is somewhat slower than the previously obtained t(-3/2) behavior in the
      decay of interlocked rings with zero magnetic helicity. We attribute the
      difference to the creation of local structures that contain magnetic helicity
      which inhibits the field decay due to the existence of a lower bound imposed by
      the realizability condition. We show that net magnetic helicity can be produced
      resistively as a result of a slight imbalance between mutually canceling helical
      pieces as they are being driven apart. We speculate that higher order topological
      invariants beyond magnetic helicity may also be responsible for slowing down the
      decay of the two more complicated nonhelical structures mentioned above.

PMID- 21867322
TI  - Resonant transparency of a two-layer plasma structure in a magnetic field.
AB  - Transparency of a two-layer plasma structure in an external steady-state magnetic
      field, perpendicular to the wave incidence plane, is studied. The case of the p
      polarized electromagnetic wave is considered. The electromagnetic wave is
      obliquely incident on the two-layer structure and is evanescent in both layers.
      The conditions for total transparency of the two-layer structure are found. The
      parametric dependencies of the transparency coefficient on the plasma slab
      widths, the magnitude of the wave number component, as well on the magnetic field
      magnitude are obtained.

PMID- 21867323
TI  - Effects of electron-ion temperature equilibration on inertial confinement fusion
      implosions.
AB  - The electron-ion temperature relaxation essentially affects both the laser
      absorption in coronal plasmas and the hot-spot formation in inertial confinement
      fusion (ICF). It has recently been reexamined for plasma conditions closely
      relevant to ICF implosions using either classical molecular-dynamics simulations
      or analytical methods. To explore the electron-ion temperature equilibration
      effects on ICF implosion performance, we have examined two Coulomb logarithm
      models by implementing them into our hydrocodes, and we have carried out
      hydrosimulations for ICF implosions. Compared to the Lee-More model that is
      currently used in our standard hydrocodes, the two models predict substantial
      differences in laser absorption, coronal temperatures, and neutron yields for ICF
      implosions at the OMEGA Laser Facility [Boehly et al. Opt. Commun. 133, 495
      (1997)]. Such effects on the triple-picket direct-drive design at the National
      Ignition Facility (NIF) have also been explored. Based on the validity of the two
      models, we have proposed a combined model of the electron-ion temperature
      relaxation rate for the overall ICF plasma conditions. The hydrosimulations using
      the combined model for OMEGA implosions have shown ~6% more laser absorption, ~6%
      15% higher coronal temperatures, and ~10% more neutron yield, when compared to
      the Lee-More model prediction. It is also noticed that the gain for the NIF
      direct-drive design can be varied by ~10% among the different electron-ion
      temperature-relaxation models.

PMID- 21867324
TI  - Ground-state structures of superparamagnetic two-dimensional dusty plasma
      crystals.
AB  - Ground-state structures of finite, cylindrically confined two-dimensional Yukawa
      systems composed of charged superparamagnetic dust grains in an external magnetic
      field are investigated numerically, using molecular dynamic simulations and
      lattice summation methods. The ground-state configuration of the system is
      identified using, as an approximation, the experimentally obtained shape of the
      horizontal confinement potential in a classical single-layer dusty plasma
      experiment with nonmagnetic grains. Results are presented for the dependence of
      the number density and lattice parameters of the dust layer on (1) the ratio of
      the magnetic dipole-dipole force to electrostatic force between the grains and
      (2) the orientation of the grain magnetic moment with respect to the layer.

PMID- 21867325
TI  - Alfven waves and ideal two-dimensional Galerkin truncated magnetohydrodynamics.
AB  - We investigate numerically the dynamics of two-dimensional Euler and ideal
      magnetohydrodynamics (MHD) flows in systems with a finite number of modes, up to
      4096(2), for which several quadratic invariants are preserved by the truncation
      and the statistical equilibria are known. Initial conditions are the Orszag-Tang
      vortex with a neutral X point centered on a stagnation point of the velocity
      field in the large scales. In MHD, we observe that the total energy spectra at
      intermediate times and intermediate scales correspond to the interactions of
      eddies and waves, E(T)(k)~k(-3/2). Moreover, no pseudodissipative range is
      visible for either Euler or ideal MHD in two dimensions. In the former case, this
      may be linked to the existence of a vanishing turbulent viscosity whereas in MHD,
      the numerical resolution employed may be insufficient. When imposing a uniform
      magnetic field to the flow, we observe a lack of saturation of the formation of
      small scales together with a significant slowing down of their equilibration,
      with however a cutoff independent partial thermalization being reached at
      intermediate scales.

PMID- 21867326
TI  - One-dimensional vertical dust strings in a glass box.
AB  - The oscillation spectrum of a one-dimensional vertical dust string formed inside
      a glass box on top of the lower electrode in a gaseous electronics conference
      (GEC) reference cell was studied. A mechanism for creating a single vertical dust
      string is described. It is shown that the oscillation amplitudes, resonance
      frequencies, damping coefficients, and oscillation phases of the dust particles
      separate into two distinct groups. One group exhibits low damping coefficients,
      increasing amplitudes, and decreasing resonance frequencies for dust particles
      closer to the lower electrode. The other group shows high damping coefficients
      but anomalous resonance frequencies and amplitudes. At low oscillation
      frequencies, the two groups are also separated by a pi phase difference. One
      possible cause for the difference in behavior between the two groups is
      discussed.

PMID- 21867327
TI  - Time- and spectrally resolved measurements of laser-driven hohlraum radiation.
AB  - At the GSI Helmholtz center for heavy-ion research combined experiments with
      heavy ions and laser-produced plasmas are investigated. As a preparation to
      utilize indirectly heated targets, where a converter hohlraum provides thermal
      radiation to create a more homogeneous plasma, this converter target has to be
      characterized. In this paper the latest results of these measurements are
      presented. Small spherical cavities with diameters between 600 and 750 MUm were
      heated with laser energies up to 30 J at 532-nm wavelength. Radiation
      temperatures could be determined by time-resolved as well as time-integrated
      diagnostics, and maximum values of up to 35 eV were achieved.

PMID- 21867328
TI  - Appearance of bound states in random potentials with applications to soliton
      theory.
AB  - We analyze the stochastic creation of a single bound state (BS) in a random
      potential with a compact support. We study both the Hermitian Schrodinger
      equation and non-Hermitian Zakharov-Shabat systems. These problems are of special
      interest in the inverse scattering method for Korteveg-de-Vries and the nonlinear
      Schrodinger equations since soliton solutions of these two equations correspond
      to the BSs of the two aforementioned linear eigenvalue problems. Analytical
      expressions for the average width of the potential required for the creation of
      the first BS are given in the approximation of delta-correlated Gaussian
      potential and additionally different scenarios of eigenvalue creation are
      discussed for the non-Hermitian case.

PMID- 21867329
TI  - Propagation of acoustic waves in a one-dimensional array of noncohesive
      cylinders.
AB  - By means of a photoelastic method, we access the visualization of acoustic waves
      propagating in a one-dimensional array of noncohesive cylinders. As pointed by
      Nesterenko in the case of spherical grains [V. F. Nesterenko, J. Appl. Mech.
      Tech. Phys. 24, p. 567 (1983)], the nonlinearity of the contact law between the
      grains induces a dependence of the wave velocity both on its amplitude and on the
      confinement force. Our experimental method allows one to access the evolution in
      time of the internal state of stress of individual grains with excellent
      accuracy. We show that the velocity of the sound presents two regimes as a
      function of the confining force. For low forces, the dependence is strongly
      nonlinear, while it weakens for higher forces. By means of the direct
      visualization of the contact zone, we show that both micro- and macroscale
      imperfections of the surface of contact explain the low forces behavior. We test
      the consistency of our experimental findings results with both the theoretical
      expectations and with the experimental determination of the force-displacement
      dependence. We show, moreover, that the main damping process originates in solid
      friction.

PMID- 21867330
TI  - Control of solitons.
AB  - A method for adiabatic control of envelope solitons in the driven nonlinear
      Schrodinger equation is developed. The approach is based on the autoresonant
      effect, when the soliton is captured ("phase locked") by a two-phase resonant
      driving with slowly varying frequencies. Threshold conditions for amplitudes and
      variation rates of the driving required for the control of both the amplitude and
      the velocity of the soliton are found. Numerical simulations demonstrate that the
      method allows one to control solitons for a long time according to a given
      scenario, while the threshold conditions are fulfilled locally.

PMID- 21867331
TI  - Dissipative rogue waves: extreme pulses generated by passively mode-locked
      lasers.
AB  - We study numerically rogue waves in dissipative systems, taking as an example a
      unidirectional fiber laser in a nonstationary regime of operation. The choice of
      specific set of parameters allows the laser to generate a chaotic sequence of
      pulses with a random distribution of peak amplitudes. The probability density
      function for the intensity maxima has an elevated tail at higher intensities. We
      have found that the probability of producing extreme pulses in this setup is
      higher than in any other system considered so far.

PMID- 21867332
TI  - Transparent uniaxial anisotropic spherical particles designed using radial
      anisotropy.
AB  - Based on Mie scattering theory and the assumption that the particle is
      electrically small in size (k(t)a?1,k(m)a?1), an analytic relationship between
      radial and tangential permittivity parameters has been established for achieving
      minimal scattering from an arbitrary rotationally uniaxial anisotropic spherical
      object incident by a plane wave. Analysis of fields in both the far- and near
      field zones indicates that the derived relation is not only valid for
      electrically small particles, but also applicable to larger ones whose sizes are
      comparable with the free space wavelength after slight adjustments in parameters.
      Furthermore, it is observed that the dielectric spherical particle of reduced
      tangential permittivity yields better transparency performance than the design
      using a plasmonic cover by Alu and Engheta [Phys. Rev. E 72, 016623 (2005)]. As
      such, particles with carefully engineered radial anisotropy are transparent
      without using any coating and are ideal for applications with space constraint
      and stringent transparency criteria.

PMID- 21867333
TI  - Analytical chirped solutions to the (3 + 1)-dimensional Gross-Pitaevskii equation
      for various diffraction and potential functions.
AB  - Analytical solutions to the (3 + 1)-dimensional Gross-Pitaevskii equation in the
      presence of chirp and for different diffraction and potential functions are
      found. We utilize a method we formulated to solve the Riccati equation for the
      chirp function that arises when the F-expansion technique and the homogeneous
      balance principle are applied to the Gross-Pitaevskii equation. Three specific
      examples of physical interest are considered in some detail.

PMID- 21867334
TI  - Effective model and investigation of the near-field enhancement and subwavelength
      imaging properties of multilayer arrays of plasmonic nanospheres.
AB  - When a small radiating or scattering object is placed near a multilayer array of
      plasmonic nanospheres, on the other side the optical near field is enhanced due
      to the excitation of resonant modes in the layers. For some particular
      frequencies, the field behind the array is concentrated in a subwavelength
      region, creating a super resolution effect. Resonating layers are able to
      reproduce (transport) part of the evanescent spectrum to the other side of these
      layers which otherwise would decay rapidly. We explore the mechanism of
      evanescent field transport and subwavelength field concentration on the other
      side of the layered material and show the relationship between near-field
      enhancement, field concentration, and modal dispersion characteristics. A
      detailed investigation of these phenomena is carried out by using an effective
      numerical model based on the array scanning method (ASM) combined with the Ewald
      method to accelerate the convergence of the dyadic Green function calculation.
      The subwavelength-sized spheres forming the arrays are represented as single
      dipole radiators, and the model of their interactions takes into account all the
      radiative and reactive field components.

PMID- 21867335
TI  - Dragging two-dimensional discrete solitons by moving linear defects.
AB  - We study the mobility of small-amplitude solitons attached to moving defects
      which drag the solitons across a two-dimensional (2D) discrete nonlinear
      Schrodinger lattice. Findings are compared to the situation when a free small
      amplitude 2D discrete soliton is kicked in a uniform lattice. In agreement with
      previously known results, after a period of transient motion the free soliton
      transforms into a localized mode pinned by the Peierls-Nabarro potential,
      irrespective of the initial velocity. However, the soliton attached to the moving
      defect can be dragged over an indefinitely long distance (including routes with
      abrupt turns and circular trajectories) virtually without losses, provided that
      the dragging velocity is smaller than a certain critical value. Collisions
      between solitons dragged by two defects in opposite directions are studied too.
      If the velocity is small enough, the collision leads to a spontaneous symmetry
      breaking, featuring fusion of two solitons into a single one, which remains
      attached to either of the two defects.

PMID- 21867336
TI  - Effective constitutive parameters of plasmonic metamaterials: homogenization by
      dual field interpolation.
AB  - We introduce a general implementation of the recently proposed homogenization
      theory [Tsukerman, J. Opt. Soc. Am. B 28, 577 (2011)] allowing one to retrieve
      all 36 linear constitutive parameters of any 3D metamaterial with
      parallelepipedal unit cells. The effective parameters are defined directly as
      linear relations between pairs of coarse-grained fields, in contrast with methods
      where these parameters are obtained from reflection and transmission data or
      other indirect considerations. The method is applied to plasmonic metamaterials
      with spherical gold particles and split-ring resonators (SRR), respectively. In
      both cases, the expected physical behavior is reproduced almost perfectly, with
      no unphysical artifacts.

PMID- 21867337
TI  - Computing periodic orbits with arbitrary precision.
AB  - This paper deals with the computation of periodic orbits of dynamical systems up
      to any arbitrary precision. These very high requirements are useful, for example,
      in the studies of complex pole location in many physical systems. The algorithm
      is based on an optimized shooting method combined with a numerical ordinary
      differential equation (ODE) solver, tides, that uses a Taylor-series method.
      Nowadays, this methodology is the only one capable of reaching precision up to
      thousands of digits for ODEs. The method is shown to be quadratically convergent.
      Some numerical tests for the paradigmatic Lorenz model and the Henon-Heiles
      Hamiltonian are presented, giving periodic orbits up to 1000 digits.

PMID- 21867338
TI  - Method for sampling compact configurations for semistiff polymers.
AB  - The sampling of compact configurations is crucial when investigating structural
      properties of semistiff polymers, like proteins and DNA, using Monte Carlo
      methods. A sampling scheme for a continuous model based on configuration biasing
      is introduced, tested, and compared with conventional methods. The proposed
      configuration biased Monte Carlo method, used together with the Wang-Landau
      sampling scheme, enables us to obtain any thermodynamic property within the
      statistical ensemble in use. Using the proposed method, it is possible to collect
      statistical data of interest for a wide range of compactions (from stretched up
      to several toroid loops) in a single computer experiment. A second-order-like
      stretched-toroid phase transition is observed for a semistiff polymer, and the
      critical temperature is estimated.

PMID- 21867339
TI  - Free energy of contact formation in proteins: efficient computation in the
      elastic network approximation.
AB  - Biomolecular simulations have become a major tool in understanding biomolecules
      and their complexes. However, one can typically only investigate a few mutants or
      scenarios due to the severe computational demands of such simulations, leading to
      a great interest in method development to overcome this restriction. One way to
      achieve this is to reduce the complexity of the systems by an approximation of
      the forces acting upon the constituents of the molecule. The harmonic
      approximation used in elastic network models simplifies the physical complexity
      to the most reduced dynamics of these molecular systems. The reduced polymer
      modeled this way is typically comprised of mass points representing coarse
      grained versions of, e.g., amino acids. In this work, we show how the computation
      of free energy contributions of contacts between two residues within the molecule
      can be reduced to a simple lookup operation in a precomputable matrix. Being able
      to compute such contributions is of great importance: protein design or molecular
      evolution changes introduce perturbations to these pair interactions, so we need
      to understand their impact. Perturbation to the interactions occurs due to
      randomized and fixated changes (in molecular evolution) or designed modifications
      of the protein structures (in bioengineering). These perturbations are
      modifications in the topology and the strength of the interactions modeled by the
      elastic network models. We apply the new algorithm to (1) the bovine trypsin
      inhibitor, a well-known enzyme in biomedicine, and show the connection to folding
      properties and the hydrophobic collapse hypothesis and (2) the serine proteinase
      inhibitor CI-2 and show the correlation to Phi values to characterize folding
      importance. Furthermore, we discuss the computational complexity and show
      empirical results for the average case, sampled over a library of 77 structurally
      diverse proteins. We found a relative speedup of up to 10 000-fold for large
      proteins with respect to repeated application of the initial model.

PMID- 21867340
TI  - Lattice Boltzmann method for one-dimensional radiation transfer.
AB  - The macroscopic conservation equations of radiation energy and radiation momentum
      are derived on the basis of radiation hydrodynamics. Based on the Chapman-Enskog
      method, the lattice Boltzmann model for one-dimensional radiative transfer is
      proposed from the Boltzmann equation. The numerical simulation results agree well
      with the exact solution and show that the lattice Boltzmann method developed in
      this paper has good accuracy and stability for solving one-dimensional radiative
      transfer problems.

PMID- 21867341
TI  - Multiple-image treatment of induced charges in Monte Carlo simulations of
      electrolytes near a spherical dielectric interface.
AB  - The polarization-induced charges of a dielectric sphere are studied for charged
      colloidal systems in electrolyte solutions with a primitive model. The method of
      constructing multiple-image charges is used to approximate the polarization
      potential of a microion outside the sphere; it is based on a numerical
      discretization of the potential's analytical integral representation, and can
      systematically approximate the exact potential with desired accuracy by
      varyiation of the number of point images. Different aspects of the image effects
      are then investigated by Monte Carlo simulations for several colloidal systems,
      in both salt-free and salty environments. Furthermore, we studied the influence
      of discrete surface charges of different valences, and demonstrate that the
      polarization charges can significantly strengthen charge reversal for the colloid
      microion complex, especially for multivalent interfacial ions.

PMID- 21867342
TI  - Approximation for discrete Fourier transform and application in study of three
      dimensional interacting electron gas.
AB  - The discrete Fourier transform is approximated by summing over part of the terms
      with corresponding weights. The approximation reduces significantly the
      requirement for computer memory storage and enhances the numerical computation
      efficiency with several orders without losing accuracy. As an example, we apply
      the algorithm to study the three-dimensional interacting electron gas under the
      renormalized-ring-diagram approximation where the Green's function needs to be
      self-consistently solved. We present the results for the chemical potential,
      compressibility, free energy, entropy, and specific heat of the system. The
      ground-state energy obtained by the present calculation is compared with the
      existing results of Monte Carlo simulation and random-phase approximation.

PMID- 21867343
TI  - Coulomb interactions in charged fluids.
AB  - The use of Ewald summation schemes for calculating long-range Coulomb
      interactions, originally applied to ionic crystalline solids, is a very common
      practice in molecular simulations of charged fluids at present. Such a choice
      imposes an artificial periodicity which is generally absent in the liquid state.
      In this paper we propose a simple analytical O(N(2)) method which is based on
      Gauss's law for computing exactly the Coulomb interaction between charged
      particles in a simulation box, when it is averaged over all possible orientations
      of a surrounding infinite lattice. This method mitigates the periodicity typical
      of crystalline systems and it is suitable for numerical studies of ionic liquids,
      charged molecular fluids, and colloidal systems with Monte Carlo and molecular
      dynamics simulations.

PMID- 21867344
TI  - Antiferromagnetic character of workplace stress.
AB  - We study the nature of workplace stress from the aspect of human-human
      interactions. We investigated the distribution of Center for Epidemiological
      Studies Depression Scale scores, a measure of the degree of stress, in
      workplaces. We found that the degree of stress people experience when around
      other highly stressed people tends to be low, and vice versa. A simulation based
      on a model describing microlevel human-human interaction reproduced this observed
      phenomena and revealed that the energy state of a face-to-face communication
      network correlates with workplace stress macroscopically.

PMID- 21867345
TI  - Flow graphs: interweaving dynamics and structure.
AB  - The behavior of complex systems is determined not only by the topological
      organization of their interconnections but also by the dynamical processes taking
      place among their constituents. A faithful modeling of the dynamics is essential
      because different dynamical processes may be affected very differently by network
      topology. A full characterization of such systems thus requires a formalization
      that encompasses both aspects simultaneously, rather than relying only on the
      topological adjacency matrix. To achieve this, we introduce the concept of flow
      graphs, namely weighted networks where dynamical flows are embedded into the link
      weights. Flow graphs provide an integrated representation of the structure and
      dynamics of the system, which can then be analyzed with standard tools from
      network theory. Conversely, a structural network feature of our choice can also
      be used as the basis for the construction of a flow graph that will then
      encompass a dynamics biased by such a feature. We illustrate the ideas by
      focusing on the mathematical properties of generic linear processes on complex
      networks that can be represented as biased random walks and their dual consensus
      dynamics, and show how our framework improves our understanding of these
      processes.

PMID- 21867346
TI  - Opening of a wall-mounted leaflet by a single flow pulse.
AB  - The opening of a leaflet by one flow pulsation is studied here in an ideal system
      made of a rigid door, initially vertical, mounted on a horizontal wall. The
      dependence of the fluid-structure interaction on the leaflet inertia and flow
      parameters has been analyzed. The system has been solved by numerical integration
      of the Navier-Stokes equations coupled with the body dynamics. The behavior of
      the movable leaflet and resulting vortex formation has been conditioned through
      the range of Strouhal numbers and body inertia. When inertia is relatively large,
      the flow pulsation is unable to significantly move the leaflet. When inertia is
      relatively low, the degree of opening smoothly increases with lowering the
      Strouhal number (that corresponds, for example, to either a longer pulsation
      period or a higher flow velocity). The analysis also demonstrated the existence
      of a critical intermediate range where the body opens completely and impacts onto
      the lower wall at high speed.

PMID- 21867347
TI  - Alcoholic liver disease, oxidative stress, and antioxidants.

PMID- 21867348
TI  - Trolox reduces the effect of ethanol on acetylcholine-induced contractions and
      oxidative stress in the isolated rabbit duodenum.
AB  - Trolox is a hydrophilic analogue of vitamin E and a free radical scavenger.
      Ethanol diminishes the amplitude of spontaneous contractions and acetylcholine
      (ACh)-induced contractions in rabbit duodenum. The aim of this work was to study
      the effect of Trolox on the alterations induced by ethanol on contractility and
      lipid peroxidation in the duodenum. The duodenal contractility studies in vitro
      were carried out in an organ bath and the levels of malondialdehyde and 4
      hydroxyalkenals (MDA+4-HAD) were measured by spectrophotometry. Trolox increased
      the reduction induced by ethanol on the amplitude of spontaneous contractions in
      longitudinal muscle but not in circular muscle. Trolox 4 mM decreased the effects
      of ethanol on ACh-induced contractions and on MDA+4-HDA concentrations. We
      conclude that Trolox might prevent oxidative stress induced by ethanol in the
      duodenum.

PMID- 21867349
TI  - Results of implementation of a fast track pathway for diagnosis of colorectal
      cancer.
AB  - INTRODUCTION: fast track pathways for diagnosis of cancer intend to decrease
      delays in diagnosis and treatment of cancer. It is recommended to initiate
      treatment in a period no longer than 30 days since admission in these circuits.
      AIMS: to know the characteristics and fluency of our Fast Track Diagnostic
      Pathway (FTDP) for Colorectal Cancer (CRC), with special attention to those
      patients selected for surgical treatment as a first choice. MATERIAL AND METHOD:
      all patients who entered the FTDP for CRC during a period of 2 years (2008-2009)
      were analyzed as well as the rest of patients also diagnosed with CRC but never
      seen in the FTDP. RESULTS: of the 316 patients referred to the FTDP only 78
      (24.7%) were diagnosed as having some kind of cancer derived from the digestive
      system. At the end 61 patients (19.3%) were diagnosed with CCR. The time interval
      from entry into the FTDP to the first hospital visit was 3 days (range 1-8), and
      the interval until colonoscopy was performed was 11.5 days (range 1-41). Fourteen
      (41.1%) of those patients chosen for surgery were operated on in a period lesser
      than 30 days while 28 patients (82.3%) underwent surgery before day 45 since
      admission into the circuit. CONCLUSIONS: though the functioning of the FTDP is
      acceptable, any increase in number of patients can generate delays. For this
      reason it is advisable to have a team to assure a good functioning of the FTDP. A
      proper follow-up of the whole process will possibly avoid unnecessary delays and
      it will improve coordination of the different phases of the fast track pathway
      and treatment. As the diagnostic outcome is poor it is mandatory to implement
      alternatives programs like screening of asymptomatic population, allowing an
      early detection of this condition.

PMID- 21867350
TI  - Colorectal cancer in the elderly: characteristics and short term results.
AB  - OBJECTIVE: to analyse the characteristics of colorectal cancer in elderly
      patients and to assess the outcomes of treatment. MATERIAL AND METHODS: the study
      included 1,924 patients diagnosed with colorectal cancer during a 22 year period
      (1985-2007). We analysed patient clinical and demographic characteristics as well
      as their treatment and its outcome. RESULTS: there was an increase in emergency
      surgery with age, increasing from 13% among patients under 80 years of age to 47%
      in those over 90 years of age (p = 0.0001). On the other hand, the overall
      percentage of patients who underwent surgical treatment decreased from 96% in
      patients younger than 80 years of age, to 85% and 59% in octogenarians and
      nonagenarians, respectively (p = 0.0001), and there was a similar pattern in the
      rates of curative surgery among patients who underwent surgery. The overall
      mortality of patients who underwent surgery was 8% (141 out of 1,769), increasing
      from 4% in patients younger than 70 years of age to 25% in those over 90 (p =
      0.0001). Multivariate analysis showed that the factors associated with mortality
      were the emergency nature of the surgery (p = 0.001), the ASA grade (p = 0.0001),
      and the presence of systemic complications (p = 0.0001), the weight of age
      decreasing significantly with respect to the univariate analysis (p = 0.013).
      CONCLUSIONS: there is an increase in the rate of complicated forms of colorectal
      cancer with increasing age of patients. In addition, there is a dramatic decrease
      in the rate of curative tumour resection with increasing age. Intraoperative
      mortality for colorectal cancer in octogenarians and nonagenarians is more
      closely related to the nature and intent of the surgery (elective or emergency;
      palliative or curative), the perioperative risk (ASA grade), and severe systemic
      complications, than to age.

PMID- 21867351
TI  - Gastric polyps: analysis of endoscopic and histological features in our center.
AB  - BACKGROUND AND OBJECTIVE: the prevalence of gastric polyps in
      esophagogastroduodenoscopies (EGDs) ranges between 0.33 and 6.35%. The relative
      frequency of histological subspecies varies widely among published series. The
      objective is to describe the endoscopic and histological characteristics of the
      polypoid lesions, and to study possible associations. MATERIAL AND METHODS: we
      retrospectively revised the EGDs done in our center in 2009. Demographic,
      endoscopic and histological data were gathered. We proceeded to a descriptive
      analysis and studied possible associations. RESULTS: gastric polypoid lesions
      were found in 269 of the 6,307 (4.2%) reviewed EGDs, 61% were found in women.
      Mean age was 64.93 years (SD: +/-15.23). A single polyp was found in 186 patients
      (69.1%), over 10 lesions appeared in 31 (11.5%). An estimated size of <= 3 mm was
      found in 108 lesions (37.2%) and greater than 10 mm in 52 cases (17.9%). Most
      lesions were sessile (90.8%). The location of 34.8% was the gastric antrum, 39.3%
      were found in the gastric body and 25.9% were in the fundus. Chronic gastritis
      was confirmed in 53.5% of the patients and 46.5% had received protom pump
      inhibitors (PPIs). Histopathological diagnosis was: hyperplastic polyps 50.9%,
      fundic gland polyps 7.4%, adenomas 3%, adenocarcinomas 1.9% and normal mucosa
      29.7%. We found no significant association between the histopathological type of
      lesions and the use of proton pump inhibitor. CONCLUSIONS: we found polypoid
      lesions in 4.2% of the EGDs. The most frequent histopathological findings were
      hyperplastic polyps (50.9%), followed by fundic gland polyps (7.4%), adenomas
      (3%), and adenocarcinomas (1.9%).

PMID- 21867352
TI  - Abdominal splenosis.
AB  - Splenosis is a benign condition caused by an ectopic autotransplantation of
      splenic tissues after splenic trauma or surgery. It usually occurs within the
      abdominal and pelvic cavity. Patients are generally asymptomatic and this entity
      is diagnosed accidentally. However, occasionally extensive abdominal splenosis
      poses a significant diagnostic dilemma for gastroenterologists, especially when
      this condition manifests as a disseminated metastatic malignant disease on
      abdominal imaging.This paper presents a concise review of the literature on this
      often misleading disorder. The crucial role of taking a thorough patient&acute;s
      medical history concerning splenic trauma in the past, the need for differential
      diagnosis of tumor-like lesions disclosed on abdominal imaging and novel
      diagnostics modalities that allow avoiding unnecessary laparotomy in case of
      abdominal splenosis are stressed.The increased prevalence of abdominal trauma due
      to road accidents and the growing armamentarium of available imaging modalities
      suggest that abdominal splenosis may be expected more often than ever.In order to
      prevent any possible diagnostic doubts and unnecessary future invasive
      examinations, confirmed splenosis should be recorded in the medical documentation
      of the patient.

PMID- 21867353
TI  - Cat scratch esophagus: a new entity to be described?

PMID- 21867354
TI  - Small bowel obstruction after ERCP.

PMID- 21867355
TI  - Hemorrhagic cholecystitis and hemobilia: two infrequent complications of systemic
      lupus erythematosus.
AB  - INTRODUCTION: the patients affected by systemic lupus erythematosus (SLE) often
      suffer gastrointestinal symptoms. The differential diagnosis should contemplate
      pathology of the gall bladder. We present the case of a patient with hemorrhagic
      lithiasic cholecystitis and hemobilia. CASE REPORT: 24 year old female diagnosed
      with SLE under treatment with Sintrom(r), Dacortin(r) and Dolquine(r) that
      presented acute lithiasic cholecystitis and hemobilia with a distal calculus.
      Cholecystectomy and aperture of the ductus choledochus were performed allowing to
      confirm the hemobilia and to extract the calculus. DISCUSSION: The treatment of
      cholecystitis in the patients with SLE is controversial due to the fact that most
      reviewed cases have been solved with cholecystectomy, or in other cases with
      conservative treatment with corticosteroids. We believe that the presence of
      cholelithiasis in a patient with SLE with pain on the right hypochondrium and
      ultrasound confirming the suspicion of cholecystitis demands a surgical treatment
      since the cause may be vascular, lithiasic or combined. Besides, the possible
      complications will not respond to pharmaceutical treatment.

PMID- 21867356
TI  - [Non polypoid hereditary colorectal cancer].

PMID- 21867357
TI  - Vaginal metastasis of colon cancer.

PMID- 21867358
TI  - Acute necrotizing esophagitis in a patient with femur fracture.

PMID- 21867359
TI  - Refractory pseudomembranous colitis.

PMID- 21867360
TI  - Splenic arterial dissection and factor V Leiden mutation causing massive spleen
      infarction.

PMID- 21867361
TI  - [Perineal pyoderma gangrenosum in a girl treated with adalimumab after infliximab
      failure].

PMID- 21867362
TI  - Intestinal obstruction due to sclerosing encapsulating peritonitis.

PMID- 21867363
TI  - Successful treatment of methemoglobinemia and acute renal failure after
      indoxacarb poisoning.
AB  - CONTEXT: We report a case of systemic toxicity induced by indoxacarb, an
      oxadiazine insecticide. Previous reports have suggested the occurrence of
      methemoglobinemia after indoxacarb ingestion, but no case of indoxacarb-induced
      systemic toxicity, such as acute renal failure, has been reported thus far. CASE
      DETAILS: A 71-year-old woman presented with indoxacarb poisoning, resulting in
      methemoglobinemia and acute renal failure. The methemoglobinemia improved after
      methylene blue administration, but rapidly progressive acute renal failure
      occurred 7 h after admission. She was treated with continuous veno-venous
      hemofiltration and intravenous sodium bicarbonate and recovered successfully.
      DISCUSSION: Ingestion of indoxacarb may produce not only methemoglobinemia, but
      also systemic toxicities like acute renal failure, which can be successfully
      treated with aggressive therapy such as continuous veno-venous hemofiltration.
      Physicians should be alert to acute renal failure as a possible complication of
      indoxacarb ingestion, and treat it accordingly.

PMID- 21867364
TI  - Zidovudine (AZT) overdose in a healthy newborn receiving postnatal prophylaxis.
AB  - CONTEXT: Pediatric medication dosing and administration, faced with inherent
      challenges of dose to body weight adjustment and variable delivery vehicles, may
      lead to inadvertent errors effectively resulting in overdose. Zidovudine (AZT), a
      nucleoside analog reverse transcriptase inhibitor (NRTI), is a commonly
      prescribed medication to treat HIV-exposed newborns, with limited overdose data
      in this patient population. Metabolic acidosis with elevated lactate is the most
      serious consequence of AZT toxicity in the adult population, associated with
      mortality. Other significant effects may include neutropenia and hepatic
      dysfunction. CASE REPORT: A 4-day-old male infant who received two inadvertent 10
      fold overdoses of AZT while being treated for HIV postnatal prophylaxis. The
      newborn developed a transient metabolic acidosis with elevated lactate that
      resolved within 24 h, a small increase in AST, and persistent neutropenia for 5
      weeks. The patient's mother cited several key factors leading to the dosing
      error. DISCUSSION: The paucity of AZT overdose data in newborns and infants
      compels this case report, which reviews the published literature and provides
      insight into prevention and improvement of pediatric patient safety.

PMID- 21867365
TI  - Seizure caused by dermal application of over-the-counter eucalyptus oil head lice
      preparation.
AB  - Natural plant oils such as eucalyptus are common worldwide in non-prescription
      natural health products. Oral ingestion of eucalyptus oil is well known to
      produce neurological symptoms and seizures; however, its dermal use is presumed
      to be safe. We describe a brief, self-limited, tonic-clonic seizure in a healthy
      4-year-old girl following dermal exposure to eucalyptus oil as directed for
      treatment of head lice. Initial symptoms were vomiting, lethargy, and ataxia
      followed by a grand mal seizure. Recovery occurred rapidly after the skin was
      washed. Health care providers should be aware that eucalyptus oil toxicity may
      occur with dermal exposure and should report additional cases.

PMID- 21867366
TI  - Ciguatera contracted by French tourists in Mauritius recurs in Senegal.

PMID- 21867367
TI  - Measurements of light at night (LAN) for a sample of female school teachers.
AB  - Epidemiological studies have shown an association between rotating shiftwork and
      breast cancer (BC) risk. Recently, light at night (LAN) measured by satellite
      photometry and by self-reports of bedroom brightness has been shown to be
      associated with BC risk, irrespective of shiftwork history. Importance has been
      placed on these associations because retinal light exposures at night can
      suppress the hormone melatonin and/or disrupt circadian entrainment to the local
      24-h light-dark cycle. The present study examined whether it was valid to use
      satellite photometry and self-reports of brightness to characterize light, as it
      might stimulate the circadian system and thereby affect BC incidence. Calibrated
      photometric measurements were made at the bedroom windows and in the bedrooms of
      a sample of female school teachers, who worked regular dayshifts and lived in a
      variety of satellite-measured sky brightness categories. The light levels at both
      locations were usually very low and were independent of the amount of satellite
      measured light. Calibrated photometric measurements were also obtained at the
      corneas of these female school teachers together with calibrated accelerometer
      measurements for seven consecutive days and evenings. Based upon these personal
      light exposure and activity measurements, the female teachers who participated in
      this study did not have disrupted light-dark cycles like those associated with
      rotating shiftworkers who do exhibit a higher risk for BC. Rather, this sample of
      female school teachers had 24-h light-dark and activity-rest patterns very much
      like those experienced by dayshift nurses examined in an earlier study who are
      not at an elevated risk of BC. No relationship was found between the amount of
      satellite-measured light levels and the 24-h light-dark patterns these women
      experienced. It was concluded from the present study that satellite photometry is
      unrelated to personal light exposures as they might affect melatonin suppression
      and/or circadian disruption. More generally, photometric devices calibrated in
      terms of the operational characteristics of the human circadian system must be
      used to meaningfully link LAN and BC incidence.

PMID- 21867368
TI  - Extended retreatment with brentuximab vedotin (SGN-35) maintains complete
      remission in patient with recurrent systemic anaplastic large-cell lymphoma.

PMID- 21867369
TI  - Effect of morning school schedule on sleep and anthropometric variables in
      adolescents: a follow-up study.
AB  - The aim of this study was to assess whether the shift from afternoon to morning
      classes reduces the duration of sleep and whether this reduction has any relation
      to body fat measurements. This is a follow-up study in which students (n = 379),
      12.4 (SD(+/-)0.7) yrs old, were evaluated before and after the school schedule
      shift, with a 1-yr interval between the first and second data collections.
      Adolescents were divided into two groups: an afternoon-morning group (students
      who shifted from afternoon to morning classes) and an afternoon-afternoon group
      (students who remained in afternoon classes). The morning schedule of classes
      lasted from 07:30 and 12:00?h, and the afternoon schedule of classes lasted from
      13:00 and 17:30?h. Self-reported bedtime, wake-up time, and time-in-bed were
      obtained. Body mass index, waist circumference, and body fat percentage were
      obtained by direct measures. The results showed a reduction of time-in-bed during
      weekdays for those students who changed to the morning session (p < .001).
      Analysis of covariance (ANCOVA) for repeated measures of anthropometric
      differences between afternoon-afternoon and afternoon-morning groups showed no
      effect of the school schedule change on weight gain. In conclusion, the time-in
      bed reduction in the period analyzed cannot be considered to be a mediating
      factor to modifications in overweight anthropometric indicators.

PMID- 21867370
TI  - Direction of causality between body fat and insulin resistance in children--a
      longitudinal study (EarlyBird 51).
AB  - OBJECTIVE: To investigate the direction of causality in the association between
      adiposity and insulin resistance in children. METHODS: Body composition by DEXA,
      and insulin resistance by HOMA-2 IR were measured annually in 238 children aged
      from 7-13 years. Longitudinal modelling was used to establish whether baseline
      and/or trends in adiposity were associated with change in IR or whether,
      conversely, baseline and/or trends in IR were associated with change in
      adiposity. RESULTS: Baseline adiposity was associated with change in IR in the
      short-term (p < 0.001) but less so in the long-term (p < 0.09) in both genders.
      Baseline IR was not associated with short-term change in adiposity in either
      gender (p > 0.42). In the long-term, baseline IR appeared to be positively
      associated with change in adiposity in boys (p = 0.02) but inversely associated
      with change in adiposity (the higher the baseline IR, the lower the gain in %fat)
      in girls (p < 0.001). CONCLUSIONS: The dominant direction of causality appears to
      be from adiposity to insulin resistance. In boys, adiposity appears to be both a
      cause and an effect of IR in the long term. In girls, however, higher insulin
      resistance appeared to limit further gain in body fat in the long term, an
      observation consistent with insulin desensitization as an adaptive response to
      weight gain.

PMID- 21867372
TI  - Multimodal control of sensors on multiple simulated unmanned vehicles.
AB  - The use of multimodal (speech plus manual) control of the sensors on combinations
      of one, two, three or five simulated unmanned vehicles (UVs) is explored. Novice
      controllers of simulated UVs complete a series of target checking tasks. Two
      experiments compare speech and gamepad control for one, two, three or five UVs in
      a simulated environment. Increasing the number of UVs has an impact on subjective
      rating of workload (measured by NASA-Task Load Index), particularly when moving
      from one to three UVs. Objective measures of performance showed that the
      participants tended to issue fewer commands as the number of vehicles increased
      (when using the gamepad control), but, while performance with a single UV was
      superior to that of multiple UVs, there was little difference across two, three
      or five UVs. Participants with low spatial ability (measured by the Object
      Perspectives Test) showed an increase in time to respond to warnings when
      controlling five UVs. Combining speech with gamepad control of sensors on UVs
      leads to superior performance on a secondary (respond-to-warnings) task (implying
      a reduction in demand) and use of fewer commands on primary (move-sensors and
      classify-target) tasks (implying more efficient operation). STATEMENT OF
      RELEVANCE: Benefits of multimodal control for unmanned vehicles are demonstrated.
      When controlling sensors on multiple UVs, participants with low spatial
      orientation scores have problems. It is proposed that the findings of these
      studies have implications for selection of UV operators and suggests that future
      UV workstations could benefit from multimodal control.

PMID- 21867374
TI  - Single-session manualized ego state therapy (EST) for combat stress injury, PTSD,
      and ASD, part 1: the theory.
AB  - Ego state therapy (EST) evolved from a psychodynamic understanding of personality
      as a product of an individual's ego states to a conceptualization of how ego
      energized and object-energized elements are bound together to cope with a
      traumatic event. Neurobiological studies now substantiate Watkins's war neuroses
      conceptualizations. Because of their severity, trauma memories are encoded in the
      subcortical-subconscious brain regions that are accessed by the single-session
      manualized EST procedure but not by the popular cognitive-behavioral management
      therapies. The imprint of the trauma is not accessible or resolvable by such top
      down verbal understanding or reframing; EST is a bottom-up therapy. Abreactive
      hypnosis facilitates ego state expression at physiologically and psychologically
      intense levels sufficient to activate subcortical processes to release affect in
      the presence of the therapist, who adds ego strength to the patient. This is
      followed by interpretation and reintegration. The result is a reconstructed
      personality that is adaptive and resilient.

PMID- 21867371
TI  - Diagnosis and treatment of mitochondrial myopathies.
AB  - Mitochondrial disorders are a heterogeneous group of disorders resulting from
      primary dysfunction of the respiratory chain. Muscle tissue is highly
      metabolically active, and therefore myopathy is a common element of the clinical
      presentation of these disorders, although this may be overshadowed by central
      neurological features. This review is aimed at a general medical and neurologist
      readership and provides a clinical approach to the recognition, investigation,
      and treatment of mitochondrial myopathies. Emphasis is placed on practical
      management considerations while including some recent updates in the field.

PMID- 21867375
TI  - Treatment of HPV with hypnosis--psychodynamic considerations of
      psychoneuroimmunology: a brief communication.
AB  - There is increasing evidence that the hypnotic cure of warts (infection by the
      human papilloma virus or HPV) results from activation of an immune response, but
      whether this is cellular or systemic is unknown. The hypnosis can be by direct
      suggestion or analytical hypnotherapy when indicated. The evidence is reviewed,
      and 4 clinical cases suggesting cellular immune response are presented.

PMID- 21867376
TI  - Hypnotizability and sensorimotor gating: a dopaminergic mechanism of hypnosis.
AB  - Dopaminergic mechanisms have been theorized to influence hypnotizability and
      sensorimotor gating. In this study, the authors investigated an association
      between sensorimotor gating, as measured by prepulse inhibition (PPI), and
      hypnotizability, as assessed by the Stanford Hypnotic Susceptibility Scale, Form
      C (SHSS:C). They found an inverse correlation between the SSHS:C and PPI. This
      finding, which replicates an earlier study, provides further evidence for a
      dopaminergic basis for hypnotizability and suggests additional avenues for
      research, including a method for possibly enhancing hypnotizability through
      pharmacological interventions.

PMID- 21867377
TI  - Use of preoperative hypnosis to reduce postoperative pain and anesthesia-related
      side effects.
AB  - The purpose of this pilot project was to test the feasibility of hypnosis as a
      preoperative intervention. The unique features of this study were: (a) use of a
      standardized nurse-delivered hypnosis protocol, (b) intervention administration
      immediately prior to surgery in the preoperative holding area, and (c) provision
      of hypnosis to breast cancer surgery patients receiving general anesthesia. A
      mixed-method design was used. Data collected from the intervention group and
      historical control group included demographics, symptom assessments, medication
      administration, and surgical, anesthesia, and recovery minutes. A semi-structured
      interview was conducted with the intervention group. A reduction in anxiety,
      worry, nervousness, sadness, irritability, and distress was found from baseline
      to postintervention while pain and nausea increased. The results support further
      exploration of the use of nurse-led preoperative hypnosis.

PMID- 21867378
TI  - Hypnosis and dental anesthesia in children: a prospective controlled study.
AB  - The authors of this prospective study initially hypothesized that hypnosis would
      lower the anxiety and pain associated with dental anesthesia. Thirty children
      aged 5 to 12 were randomly assigned to 2 groups receiving hypnosis (H) or not
      (NH) at the time of anesthesia. Anxiety was assessed at inclusion in the study,
      initial consultation, installation in the dentist's chair, and at the time of
      anesthesia using the modified Yale preoperative anxiety scale (mYPAS). Following
      anesthesia, a visual analogue scale (VAS) and a modified objective pain score
      (mOPS) were used to assess the pain experienced. The median mYPAS and mOPS scores
      were significantly lower in the H group than in the NH group. Significantly more
      children in the H group had no or mild pain. This study suggests that hypnosis
      may be effective in reducing anxiety and pain in children receiving dental
      anesthesia.

PMID- 21867379
TI  - Waking EEG spectral power and coherence differences between high and low
      hypnotizable subjects.
AB  - EEG spectral power and coherence were analyzed under waking baseline condition in
      19 high (HH) and 12 low (LH) hypnotizable subjects. In HH subjects, the theta1
      and theta2 spectral power was higher than in LH. The major new finding of this
      study is that coherence between distributed brain regions was sharply elevated in
      HH subjects within the theta and alpha frequency bands. In contrast, spectral
      power and coherence of beta2 and gamma1 bands were higher in LH subjects as
      compared to HH subjects. However, the long distance coherence between frontal and
      posterior areas within beta-gamma frequency ranges was higher in HH subjects. It
      might be supposed that HH subjects are engaged in imaginal mental activity
      whereas LH ones are mainly engaged in linguistic activity. The neurophysiological
      basis of the obtained EEG differences is discussed.

PMID- 21867380
TI  - Effects of hypnotic focused analgesia on dental pain threshold.
AB  - The rate, intensity, and selectivity of hypnotic focused analgesia (HFA) were
      tested with dental pulp stimulation. Thirty-one healthy subjects were hypnotized,
      and hypnotic suggestions were given for anesthesia of the right mandibular arch.
      A posthypnotic suggestion of persisting analgesia was also given. The pain
      threshold of the first premolar was bilaterally measured before, during, and
      after hypnosis using a pulp tester. During hypnosis, the pain threshold increased
      significantly (p < .0001) for both sides. The posthypnotic right pain threshold
      was also significantly (p < .0015) higher than in the basal condition.

PMID- 21867381
TI  - Hypnosis in the laboratory creates a window on psychopathology.
AB  - The authors describe 3 studies in which hypnosis itself is not studied but
      instead used to create anomalous states in the laboratory that can be studied
      under controlled conditions. The 1st article is a comprehensive review of
      programmatic research using hypnosis to elicit and study clinically relevant
      delusions. The 2nd article reviews studies comparing the brain activity of
      hysterical/dissociative patients with nonpatients hypnotized and given
      suggestions for sensory-motor and cognitive anomalies typical of the clinical
      syndromes. The authors conclude that the hypnosis analogues are relevant and
      revealing. The 3rd article describes a single experiment using hypnosis to elicit
      distressing and intrusive memories, typical of acute anxiety disorders. Findings
      with hypnotic subjects are in keeping with those from patients suffering
      intrusive memories. Across all 3 papers, hypnosis is shown to be a viable and
      helpful tool for experimental psychopathology.

PMID- 21867382
TI  - Simvastatin protects against the development of monocrotaline-induced pulmonary
      hypertension in rats via a heme oxygenase-1-dependent pathway.
AB  - Heme oxygease-1 (HO-1) is the rate-limiting enzyme in heme catabolism. Induction
      of HO-1 has been shown to have vasodilatory, anti-inflammatory, and proapoptotic
      effects. More recently, experimental studies suggested the potential of
      simvastatin as a novel therapy for pulmonary hypertension (PH); however, the
      underlying mechanism remains to be investigated. The aim of this study was to
      evaluate whether HO-1 is required for the pulmonary vascular protective effects
      of simvastatin. Simvastatin (2 mg/kg/day) was administered once daily to rats for
      4 weeks after monocrotaline (MCT) injection. Zn-protoporphyrin (Znpp), a potent
      inhibitor of HO, was used to confirm the role of HO-1. The hemodynamic changes,
      right heart hypertrophy, interleukin-6 (IL-6) level, and HO-1 protein expression
      in lungs were measured at day 28. Simvastatin significantly ameliorated mean
      pulmonary arterial hypertension (20.6 mm Hg). In addition, perivascular
      infiltration of inflammatory cells and the level of IL-6 were decreased in
      simvastatin treatment group. Simvastatin also increased significantly lung HO-1
      protein expression. Inhibiting HO-1 using Znpp resulted in a loss of the effect
      of simvastatin in MCT rats. These results suggest that HO-1 expression is
      critical for the vascular protective effects of simvastatin in MCT-induced PH
      rats.

PMID- 21867383
TI  - Epigen is induced during the interleukin-13-stimulated cell proliferation in
      murine primary airway epithelial cells.
AB  - Airway remodeling in bronchial asthma is characterized by epithelial detachment
      and proliferation, subepithelial fibrosis, increased smooth muscle mass, and
      goblet cell hyperplasia. These features are mediated by T-helper type 2 (Th2)
      cytokines including interleukin (IL)-13. However, the direct effects of IL-13 on
      the functions of airway epithelial cells are not fully understood. Murine primary
      airway epithelial (MPAE) cells were cultured in an air-liquid interface (ALI)
      culture system. AG1478, a specific inhibitor of epidermal growth factor receptor
      (EGFR) tyrosine kinase, was used to examine whether EGFR was involved in the IL
      13-stimulated proliferation of MPAE cells. The expressions of EGFR ligands were
      investigated by reverse transcriptase-polymerase chain reaction, Western
      blotting, and immunohistochemical analyses. The cell counting in cross-sections
      and [(3)H]thymidine incorporation assays revealed a significant increase in the
      number of MPAE cells cultured with IL-13 compared with a phosphate-buffered
      saline (PBS) control. AG1478 abolished the IL-13-stimulated proliferation of MPAE
      cells. The expression of epigen, one of the EGFR ligands, was enhanced in MPAE
      cells cultured with IL-13. The findings suggest that EGFR is involved in the IL
      13-stimulated proliferation of MPAE cells, and that epigen is important for the
      proliferation process in airway remodeling.

PMID- 21867384
TI  - Do people with dementia find lies and deception in dementia care acceptable?
AB  - OBJECTIVES: Research suggests that the use of lies and deception are prevalent in
      dementia care settings. This issue has been explored from the view point of
      carers and professionals, and the acceptability and ethicality of deception in
      dementia care remains an area of heated debate. This article explored the issue
      of lies and deception in dementia care from the unique perspective of the people
      being lied to: People with Dementia. METHOD: This study used a qualitative
      methodology, specifically, Grounded Theory (GT). The study used a two-phased
      design. Phase one involved a series of one-to-one interviews with People with
      Dementia. During phase two, the participants were re-interviewed in order to
      develop the emerging theory. RESULTS: Lies were considered to be acceptable if
      told in People with Dementia's best interest. This best interest decision was
      complex, and influenced by factors such as the person with dementia's awareness
      of the lie, and the carer's motivation for lying. A model depicting these factors
      is discussed. CONCLUSION: This study enables the perspective of People with
      Dementia to be considered, therefore providing a more complete understanding of
      the use of deceptive practices in dementia care settings. This study suggests
      that the use of lies and deception in dementia care warrants further
      investigation.

PMID- 21867385
TI  - Common-sense beliefs about the prevention of Alzheimer's disease.
AB  - OBJECTIVES: Common-sense illness beliefs are important because they influence
      actions that people take to prevent and treat disease. This research (1) asked
      younger and older adults about their illness representations of Alzheimer's
      disease (AD) and (2) manipulated beliefs about AD preventability to determine
      causal relationships in the data. METHOD: In Study 1, the beliefs of younger (age
      18-38; n = 82) and older (age 58-89; n = 57) adults about the causes of and ways
      to prevent AD were compared. In Study 2, younger adults were randomly assigned to
      read information stating either that AD can be prevented or not. RESULTS:
      Compared to younger adults, older adults saw themselves as less at risk, t(137) =
      3.03, p = 0.003, d = 0.52, were more likely to believe that AD is preventable,
      t(137) = 5.01, p < 0.001, d = 0.87 and were more likely to report engaging in
      behaviors to prevent AD, chi(2)(1, 139) = 19.01, p < 0.001, r = 0.37.
      Manipulating beliefs in Study 2 caused those told that AD was preventable to see
      themselves as less at risk, report more prevention behaviors, and hold those with
      the disease more responsible for their fate. CONCLUSION: These findings highlight
      the association of illness representations with reports of behavior and show a
      disconnect between beliefs and what we currently know about AD.

PMID- 21867386
TI  - Developing the research hypothesis.
AB  - The research hypothesis is needed for a sound and well-developed research study.
      The research hypothesis contributes to the solution of the research problem.
      Types of research hypotheses include inductive and deductive, directional and non
      directional, and null and alternative hypotheses. Rejecting the null hypothesis
      and accepting the alternative hypothesis is the basis for building a good
      research study. This work reviews the most important aspects of organizing and
      establishing an efficient and complete hypothesis.

PMID- 21867387
TI  - Beyond the radiograph: radiological advances in surgery.
AB  - Advancements in imaging techniques and the development of new radiological
      modalities have opened exciting venues for furthering surgical specialties. From
      the initial and innovative discovery of the radiograph by Roentgen, radiology has
      found an important and central role in the expansion of surgical possibilities.
      In this historical review, the innovation and discoveries behind the development
      of the radiograph, fluoroscopy, angiography and ultrasound are examined.
      Additionally, the use of these imaging modalities in surgery is discussed.
      Learning from the discoveries of history's giants, we hope to advance our own
      knowledge and create new possibilities, a future that will hold great promise for
      the radiologists and surgeons of tomorrow.

PMID- 21867388
TI  - Late polypropylene mesh susceptibility to infection during intra-abdominal
      sepsis.
AB  - PURPOSE: To evaluate the susceptibility of high-density polypropylene mesh to
      contamination, 1 year after experimental hernia repair. METHODS: Wistar rats were
      randomized into two groups: one experimental group (n = 20) and another control
      group (n = 10). Mesh hernia repair was performed with intra-abdominal (group I, n
      = 10) or subcutaneous (group II, n = 10) implantation of grafts. The three groups
      were exposed to an intra-abdominal E. coli administration after 1 year of
      operation. After 24 hr, the meshes and peritoneum were sampled from the
      experimental and control groups, respectively, in order to assess bacterial
      inoculation. Immunoreaction to E. coli inoculation was also evaluated after 24 hr
      by measuring serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels.
      RESULTS: Bacteriological analysis revealed increased contamination in groups I
      and II when compared with the control group (p = .001 and .007, respectively). IL
      6 levels were increased in both groups I and II compared with the control group,
      24 hr after E. coli injection (p = .034 and .022, respectively), while there was
      no statistically significant difference between groups concerning the
      concentration of CRP. CONCLUSIONS: Polypropylene mesh is vulnerable to bacterial
      inoculation during intra-abdominal sepsis 1 year after mesh placement.

PMID- 21867389
TI  - The efficacy of Ankaferd Blood Stopper for the management of bleeding following
      total thyroidectomy.
AB  - PURPOSE: Postoperative hematoma remains an uncommon but potentially life-threaten
      complication of thyroid surgery. The aim of this study is to assess the efficacy
      of Ankaferd Blood Stopper (ABS) in comparison to hemostasis by conventional
      technique (HCT) for the controlling of oozing-type bleeding following total
      thyroidectomy. METHODS: We randomized 61 patients with benign euthyroid
      multinodular goiter who underwent total thyroidectomy subject to one of the two
      different hemostasis techniques. There were 31 patients in the HCT group and 30
      patients in the ABS group. The study was designed prospectively to compare ABS
      and HCT groups in terms of operation time, postoperative drainage, duration of
      postoperative stay, and complications. RESULTS: Mean postoperative drainage from
      the closed suction drains at first 24 hr were 24.6 +/- 8.6 ml and 12.0 +/- 9.2 ml
      (p = .001) and mean total postoperative drainage were 38.5 +/- 13.2 ml and 20.6
      +/- 12.2 ml (p = .001) in the HCT and ABS groups, respectively, indicating
      statistically significant differences. CONCLUSIONS: On the basis of the results
      of this trial, the use of ABS seems to be more effective than HCT to control
      hemorrhage following total thyroidectomy.

PMID- 21867390
TI  - Enoxaparin effect on malondialdehyde levels in laparoscopic cholecystectomy.
AB  - INTRODUCTION: This study was established to assess the effects of low dose
      enoxaparin on plasma malondialdehyde levels during laparoscopic cholecystectomy
      as a model of ischemia-reperfusion. MATERIALS AND METHODS: Fifty patients,
      scheduled for laparoscopic cholecystectomy, were randomized into two groups of 25
      patients in each. In enoxaparin group, patients had 20 mg/0.2 ml subcutaneous
      (sc) enoxaparin 2 hr before surgery. Blood samples were obtained for
      malondialdehyde, alanine transferase, aspartate transferase, measurements before
      the insufflation, 1 min before deflation, and 20 min after deflation. RESULTS:
      Plasma malondialdehyde concentrations were insignificant between enoxaparin and
      control groups before insufflation (1.64 +/- 2.66 vs. 2.45 +/- 4.42 MUmol l(-1);
      p = 0.44) and 1 min before deflation (1.55 +/- 2.61 vs. 3.66 +/- 5.68 MUmol l(
      1); p = 0.38). Malondialdehyde levels significantly increased in control group 20
      min after deflation in respect to enoxaparin group (1.52 +/- 2.67 vs. 6.04 +/-
      7.85 MUmol l(-1)), (p = 0.049). In control group, plasma malondialdehyde
      concentrations increased significantly compared with initial level throughout the
      study (p = 0.001). Within enoxaparin group, no statistically significant change
      was observed (p = 0.28). Plasma alanine transferase and aspartate transferase
      levels increased similarly in both groups during the study (p > 0.05). Alanine
      transferase and aspartate transferase increases within each group were
      statistically significant for all times (p < 0.05). DISCUSSION AND CONCLUSIONS:
      As a conclusion, mini dose of enoxaparin used sc'ly 2 hr before the operation,
      prevented the malondialdehyde increase during reperfusion period after
      laparoscopic cholecystectomy without causing any bleeding disorder while having
      no effect on serum alanine transferase, aspartate transferase increase.

PMID- 21867391
TI  - A new model for repair of the Achilles tendon in the rat.
AB  - The Sprague-Dawley rat is an excellent model for studies of Achilles tendon
      repair. Most researchers use a modification of the Kessler technique for suture
      repair of the Achilles tendon in rats. While this technique provides adequate
      strength, early mobilization is not recommended. Prior to healing, the load will
      be borne completely by the suture repair, subjecting it to rupture. To prevent
      this complication, investigators employing the Kessler repair often immobilize
      the operative extremity with a cast or splint. This has also been shown to be
      detrimental to the peak load borne by the tendons prior to rupture. A double-loop
      locking technique of suture repair for rat Achilles tendons is favored over the
      modified Kessler technique. As force is applied across the repair, the suture
      pulls on the tendon, sharing the load. This allows for early mobilization of
      repaired tendons, with minimal risk of rupture. Additionally, no immobilization
      is required for the operative extremity. One hundred repairs have been performed
      using this double-loop locking technique. All animals have been able to mobilize
      with minimal limp immediately after recovering from anesthesia, and there have
      been no ruptures. No other complications have occurred (hematoma, seroma,
      infection, dehiscence). This technique of tendon repair is ideal for use in
      studies of tendon repair in the rat, since it is easy to perform and eliminates
      the need for immobilization of the operative leg.

PMID- 21867392
TI  - Internal aortic annuloplasty: a novel technique.
AB  - BACKGROUND: The purpose of this study was to define an experimental model and a
      reproducible surgical technique for the preclinical assessment of safety and
      biocompatibility of a novel intra-annular internal aortic annulus repair device.
      METHODS: Adult sheep were implanted with HAART Inc's 19 mm aortic annulus repair
      device via a transverse aortotomy using standard anesthetic, surgical, and
      cardiopulmonary bypass techniques. Animals were closely monitored throughout the
      study period until the time of elective sacrifice at 30 or 60 days. RESULTS: Six
      adult sheep, mean age 63.2 weeks, mean weight 68.8 kg, underwent aortic
      annuloplasty with a 19 mm annuloplasty frame. Five of the sheep remained stable
      until scheduled sacrifice. The primary outcome of this study was animal
      mortality. Early mortality was seen in only one animal (16.7%), due to a surgical
      complication. Mild-to-moderate aortic insufficiency was observed in all animals
      upon echocardiographic examination at the time of elective sacrifice.
      CONCLUSIONS: Of the six animals that underwent aortic annuloplasty, there was one
      early death due to surgical complication. The remaining five subjects were
      clinically stable at the time of elective sacrifice. Any conclusions regarding
      the cause of the observed aortic insufficiency are beyond the scope of this
      feasibility study but would need to be fully evaluated in the preclinical
      assessment of any internal aortic annuloplasty device. We have shown that we have
      developed a reproducible surgical technique in a physiologically appropriate
      model for the preclinical assessment of internal aortic annulus repair devices.

PMID- 21867393
TI  - Chronic hernia repair in a rat model using small intestinal submucosa.
AB  - BACKGROUND. Small intestinal submucosa (SIS) body wall defect repair in
      preclinical studies results in host tissue that resembles original host tissue
      histologically and has adequate strength to maintain repair integrity. However,
      these studies have been performed using acute hernia models that may not
      represent healing in a naturally occurring hernia. METHODS. Fifty-four male
      Sprague-Dawley rats were divided into nine groups (n = 6) and
      fascia/muscle/peritoneal abdominal wall defects were created. One control group
      had no surgery. Four surgery groups had defects repaired immediately by (1)
      fascia suture apposition, (2) polypropylene mesh (PPM) peritoneal onlay, (3) SIS
      inlay, or (4) SIS peritoneal onlay. After defect creation, chronic hernias
      matured for 28 days, and then were similarly repaired. Follow-up after hernia
      repair for all groups was 28 days. Gross evaluation for hernia recurrence,
      infection, and adhesions was followed by histopathology and tensile testing of
      the repair. RESULTS. There were no recurrent hernias or infection. Adhesions
      covered all implants. Histopathologic findings of inflammation and fibrosis were
      similar between all groups. There were no significant differences in tensile
      strength between SIS and PPM healing/incorporation or between acute and chronic
      hernia groups. Normal body wall was stronger than all repairs. Fascia closure in
      chronic hernias was stronger than acute fascia closure (p < .01). CONCLUSIONS. We
      found no significant differences between SIS and PPM healing/incorporation as
      determined by gross and histopathology and tensile strength testing. The study
      suggests that preclinical testing of abdominal body wall reconstruction in the
      rat may be adequately performed in acute studies.

PMID- 21867394
TI  - Simultaneous determination of three polyphenols in rat plasma after orally
      administering hawthorn leaves extract by the HPLC method.
AB  - A simple and sensitive HPLC method was developed to simultaneously determine
      three active compounds, vitexin-4"-O-glucoside (VG), vitexin-2"-O-rhamnoside (VR)
      and hyperoside (HP), in rat plasma after administering the hawthorn leaves
      extract (HLE). An HPLC assay with baicalin as the internal standard was carried
      out using a Phenomsil C18 analytical column with UV detection at 332 nm. The
      mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic
      acid (6 : 1.5 : 18.5 : 74, v/v/v/v). The calibration curves were linear over the
      range of 2.5-500, 0.2-25 and 0.25-12.5 ug mL-1 for VG, VR and HP, respectively.
      The method was reproducible and reliable, with relative standard deviations of
      the intra- and inter-day precision between 1.2% and 13.2% for the analysis of the
      three analytes. The validated HPLC method herein described was successfully
      applied to the pharmacokinetic study of VG, VR and HP after oral administration
      of HLE to rats over the dose range of 2.5-10  mL kg-1.

PMID- 21867395
TI  - Examining predictors of physical activity among inactive middle-aged women: an
      application of the health action process approach.
AB  - This study tested several relationships predicted by the Health Action Process
      Approach (HAPA) in a sample of 175 generally healthy, inactive, middle-aged women
      (40-65 yrs old) over a 12 week period. Participants' physical activity, risk
      perceptions, outcome expectancies, action self-efficacy and intention were
      measured at baseline. Planning and maintenance self-efficacy were measured 4
      weeks later. Physical activity behaviour was measured 12 weeks after baseline.
      The HAPA relationships were examined using a structural equation model. The data
      fit the model well and revealed several significant relationships. Action self
      efficacy was the best predictor of intention. Maintenance self-efficacy was the
      best predictor of planning and behaviour. Contrary to the tenets of HAPA and to
      past research, planning did not predict behaviour. Overall, HAPA provides a
      useful framework for identifying determinants of physical activity intentions and
      behaviour within a group of inactive, middle-aged women.

PMID- 21867396
TI  - Countertransference in the treatment of adolescents and its manifestation in the
      therapist-patient relationship.
AB  - Countertransference is a central construct in the clinical literature (Freud,
      1910; Gabbard, 2001), yet it has generated very little research to date. The
      present study used the CCRT method (Luborsky & Crits- Cristoph, 1998) to measure
      countertransference themes in a sample of 12 therapists, who described
      relationship episodes with their parents and with two clients. Results showed
      high repetitiveness of the parent themes in the narratives about the patients for
      all three components of the CCRT: Wish, Response of Other and Response of Self. A
      qualitative analysis of the narratives generated four countertransference
      dynamics: Repeating the parent RO, repairing the parent RO, identification with
      the patient, and withdrawing. It is suggested that these four dynamics constitute
      the process which links the origins and triggers with the manifestations and
      effects in Hayes's (2004) operational model of countertranference.

PMID- 21867397
TI  - Affective and health-related outcome expectancies for physical activity in older
      adults.
AB  - This study tests the effects of affective and health-related outcome expectancies
      on physical exercise, assuming stronger direct and indirect (via intention)
      effects from affective outcome expectancy to physical exercise than from health
      related outcome expectancy to exercise. Physical exercise and social cognitive
      variables were assessed at baseline, and 6- and 12-month follow-up in 335 older
      adults (60-95 years of age). Applying structural equation modelling, there was a
      direct effect from affective, but not from health-related outcome expectancy on
      intentions and behaviour. Also, the indirect effect from self-efficacy on
      physical exercise via affective outcome expectancy was significant, whereas the
      mediation via health-related outcome expectancy was not. These findings emphasise
      the relative importance of affective versus health-related outcome expectancies
      in predicting intentions and physical exercise in older adults and highlight the
      importance to separate these facets at a conceptual level to enhance both theory
      development and health promotion.

PMID- 21867398
TI  - Nonviral gene delivery with the sleeping beauty transposon system.
AB  - Effective gene therapy requires robust delivery of therapeutic genes into
      relevant target cells, long-term gene expression, and minimal risks of secondary
      effects. Nonviral gene transfer approaches typically result in only short-lived
      transgene expression in primary cells, because of the lack of nuclear maintenance
      of the vector over several rounds of cell division. The development of efficient
      and safe nonviral vectors armed with an integrating feature would thus greatly
      facilitate clinical gene therapy studies. The latest generation transposon
      technology based on the Sleeping Beauty (SB) transposon may potentially overcome
      some of these limitations. SB was shown to provide efficient stable gene transfer
      and sustained transgene expression in primary cell types, including human
      hematopoietic progenitors, mesenchymal stem cells, muscle stem/progenitor cells
      (myoblasts), induced pluripotent stem cells, and T cells. These cells are
      relevant targets for stem cell biology, regenerative medicine, and gene- and cell
      based therapies of complex genetic diseases. Moreover, the first-in-human
      clinical trial has been launched to use redirected T cells engineered with SB for
      gene therapy of B cell lymphoma. We discuss aspects of cellular delivery of the
      SB transposon system, transgene expression provided by integrated transposon
      vectors, target site selection of the transposon vectors, and potential risks
      associated with random genomic insertion.

PMID- 21867399
TI  - Inhaled whole exhaust and its effect on exercise performance and vascular
      function.
AB  - CONTEXT: Internal combustion engines are a major source of particulate matter
      (PM) which has been shown to result in vasoconstriction, yet no present study to
      our knowledge has investigated the effect of exhaust emissions on both exercise
      performance and the vasculature. OBJECTIVE: To examine the effect of freshly
      generated whole exhaust on exercise performance, pulmonary arterial pressure
      (PP), and flow-mediated vasodilation (FMD) of the brachial artery. MATERIALS AND
      METHODS: Sixteen male, collegiate athletes (age: 20.8+/-1.28 years) were randomly
      assigned to submaximal exercise for 20 min followed by a 6 min maximal work
      accumulation exercise test in either high PM (HPM) or low PM (LPM) conditions on
      two consecutive days. After a 7-day washout period, subjects completed identical
      exercise trials in the alternate condition. HPM conditions were generated from a
      4-cycle gasoline engine. The participants' PP and FMD were assessed before and
      after each exercise trial by tricuspid regurgitant velocity and brachial artery
      imaging, respectively. RESULTS: Total work (LPM: 108.0+/-14.8 kJ; HPM: 104.9+/
      15.2 kJ, p=0.019) and FMD (LPM: 8.17+/-6.41%; HPM: 6.59+/-2.53%; p=0.034)
      significantly decreased in HPM while PP was significantly increased (LPM: 16.9+/
      1.13 mmHg; HPM: 17.9+/-1.70 mmHg; p=0.004). A significant correlation was
      identified between the change in exercise performance and the change in FMD
      (r=0.494; p=0.026) after the first HPM trial. CONCLUSION: Exercise performance
      declined in HPM conditions in part due to impaired vasodilation in the peripheral
      vasculature.

PMID- 21867400
TI  - Rotigotine transdermal patch in combination therapy for Parkinson's disease-
      observations in routine clinical practice.
AB  - OBJECTIVE: The dopamine agonist rotigotine has shown efficacy and safety for the
      treatment of early and advanced Parkinson's disease (PD) in controlled clinical
      trials. This observational study evaluated rotigotine administration in
      combination with other antiparkinsonian medication in routine clinical practice.
      METHODS: Data were collected by 688 German practice-based neurologists,
      initiating rotigotine treatment in patients with idiopathic Parkinson's disease.
      Assessments included rotigotine maintenance dose, changes in concomitant PD
      medication, changes in sleep quality, and rotigotine tolerability over an
      observation period of 12-16 weeks. RESULTS: The median rotigotine maintenance
      dose was 6 mg/24 h (n = 969, full analysis set). The proportion of all other
      prescribed PD medications declined over the observation period; combination
      therapy decreased by 18.7%. Daily levodopa intake was markedly reduced by 87 mg
      (18.9%) in 47.6% of the patients with levodopa documentation; 7% no longer
      required levodopa after 12-16 weeks. Mean overall sleep quality (PD Sleep Scale
      item 1) improved by 21.4 points, the occurrence of nocturias (PDSS item 8) by
      13.4 points, and 'turning in bed' (Unified Parkinson's Disease Rating Scale part
      II) by 0.6 points. Drug-related adverse events were reported for 7.9% of all
      patients (n = 1152, safety population). Application site reactions were the most
      common adverse events (2.2%) resulting in early discontinuation in 1.4% of
      patients. CONCLUSIONS: In routine clinical practice, treatment initiation with
      rotigotine transdermal patch was associated with a reduction of other prescribed
      PD medications and with an improvement of self-reported sleep quality.

PMID- 21867401
TI  - Long-term evaluation of safety and health-related quality of life in women with
      heavy menstrual bleeding treated with oral tranexamic acid.
AB  - AIMS: A multicenter, long-term, open-label study was conducted to assess the
      safety and health-related quality of life (HRQoL) of an oral tranexamic acid (TA)
      formulation in women with cyclic heavy menstrual bleeding (HMB). MATERIALS &
      METHODS: Following a screening menstrual cycle, women with a history of cyclic
      HMB initiated 27 cycles of treatment with TA 1.3 g administered three-times daily
      for up to 5 days per menstrual cycle (maximum of 15 doses). Safety was assessed
      by treatment-emergent adverse event (TEAE) monitoring, physical examinations,
      laboratory results, ophthalmologic examinations and electrocardiography. HRQoL
      was evaluated using both generic and HMB-specific instruments. RESULTS: Most of
      the TEAEs were mild to moderate in severity and were largely considered unrelated
      to study treatment. The most commonly reported TEAEs among women in the intent-to
      treat population (n = 723) were headache, menstrual discomfort and back pain.
      Improvements in generic and disease-specific HRQoL measures were evident during
      the first treatment cycle and were maintained throughout the 15 cycles of
      measurement for most domains. CONCLUSION: Long-term TA treatment was well
      tolerated and improved measures of HRQoL in women with cyclic HMB.

PMID- 21867403
TI  - Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and
      methadone tapers: can we assure the safety of the fetus?
AB  - An intrauterine abstinence syndrome (IAS) is a potentially fatal consequence of
      maternal opiate withdrawal. This study reviews the evidence for this syndrome.
      Withdrawal also creates an adverse environment for the developing fetal brain
      that can have long-term health effects. Effective methadone treatment eliminates
      risks of fetal withdrawal. However, concerns about neonatal abstinence syndrome
      (NAS) in methadone-exposed neonates have resulted in efforts to withdraw women
      from methadone during pregnancy or to use buprenorphine, a mixed
      agonist/antagonist opiate in place of methadone. Both approaches necessarily
      expose the fetus to either acute or chronic withdrawal. Routine fetal monitoring
      is not able to detect such symptoms, unless they are life-threatening. Therefore,
      the safety of the fetus during buprenorphine inductions or methadone tapers
      cannot be assured and the fetus should be protected from such procedures. Further
      research into methods of diagnosing IAS and its developmental consequences is
      needed to assure that attempts to reduce NAS do not harm the fetus.

PMID- 21867404
TI  - Creatinaemia at birth is equal to maternal creatinaemia at delivery: does this
      paradigm still hold?
AB  - OBJECTIVE: The paradigm that creatinaemia at birth is equal to maternal
      creatinaemia may also depend upon the quantification technique applied. Paired
      maternal-neonatal creatinaemia samples in whom Jaffe in both or compensated Jaffe
      (maternal) and enzymatic quantification (neonate) were applied. METHODS: Extreme
      low birth weight infants in two time intervals were included when paired maternal
      neonatal creatinaemia samples were available. In cohort 1 (2000-2005),
      creatinaemia (mothers and neonates) was based on Jaffe assay. In cohort 2 (2007
      2010), maternal creatinaemia was based on compensated Jaffe. In neonates, an
      enzymatic technique was applied. Unpaired Mann Whitney U, paired Wilcoxon and
      Bland-Altman were used. RESULTS: Based on 80 and 52 paired creatinaemia samples,
      there was no significant difference between maternal (0.80, 0.41-1.6 mg.dl(-1))
      and neonatal creatinaemia (0.78, 0.31-1.46 mg.dl(-1)) in cohort 1 while a
      significant difference (p < 0.001) between maternal (0.6, 0.29-2.24 mg.dl(-1))
      and neonatal creatinaemia (0.67, 0.4-2.2 mg.dl(-1)) was observed for cohort 2.
      Using Bland-Altman, the fit was perfect for cohort 1 (mean diff -0.02 mg.dl(-1)),
      but not for cohort 2 (-0.08 mg.dl(-1)). CONCLUSIONS: The quantification method
      affects the paradigm that creatinaemia at birth is similar to maternal
      creatinaemia. Maternal and neonatal creatinaemia values depend on the method
      used. Consequently, method-specific reference values are needed.

PMID- 21867402
TI  - Late-onset preeclampsia is associated with an imbalance of angiogenic and anti
      angiogenic factors in patients with and without placental lesions consistent with
      maternal underperfusion.
AB  - OBJECTIVE: An imbalance between maternal angiogenic/anti-angiogenic factors
      concentrations has been observed in preeclampsia (PE) and other obstetrical
      syndromes. However, the frequency of pathologic findings in the placenta and the
      changes in maternal plasma angiogenic/anti-angiogenic factor concentrations
      differ between late- and early-onset PE. The aim of this study was to determine
      if the maternal plasma concentrations of placental growth factor (PlGF), soluble
      endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2
      (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental
      pathologic findings consistent with maternal underperfusion. STUDY DESIGN: A
      cross-sectional study was conducted including 64 uncomplicated women and 66 women
      with late-onset PE (>34 weeks) who had blood samples and placenta available for
      pathologic examination. Patients with late-onset PE were divided into those with
      and without placental histologic findings consistent with maternal underperfusion
      as proposed by the Society for Pediatric Pathology. Maternal plasma
      concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non
      parametric statistics were used for analysis. RESULTS: 1) the prevalence of
      placental histological findings consistent with maternal underperfusion among
      women with late-onset PE was higher than that of those with an uncomplicated
      pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p < 0.01); 2) patients with
      late-onset PE and histological findings consistent with maternal underperfusion
      had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR
      1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without
      placental underperfusion lesions (each p < 0.05); 3) the most common pathological
      findings in the placenta of patient with PE were lesions consistent with villous
      changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found
      only in 2 cases (6.5%), and the rest had a combination of villous and vascular
      lesions. CONCLUSIONS: Nearly half of the patients with late-onset PE have
      placental lesions consistent with maternal underperfusion. These lesions are
      associated with an imbalance in the maternal concentration of angiogenic/anti
      angiogenic factors. We propose that there is a link between maternal
      underperfusion and an anti-angiogenic state characterized by the changes in the
      concentrations of angiogenic and anti-angiogenic factors in women with late onset
      PE.

PMID- 21867405
TI  - Normal range of intracranial translucency (IT) assessed by three-dimensional
      ultrasound at 11 + 0 to 13 + 6 weeks in a Chinese population.
AB  - OBJECTIVES: To establish the reference range of intracranial translucency (IT) in
      the first trimester in a Chinese population. METHODS: In a prospective study from
      March 2007 to June 2007, three-dimensional (3D) volumes of the fetal profile in
      the mid-sagittal plane were recorded from 102 normal pregnancies screened for
      trisomy 21 by the combination of fetal nuchal translucency (NT) thickness,
      maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy
      associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks. 3D volumes were
      examined using multiplanar techniques. In the mid-sagittal plane the fourth
      ventricle presents as an (IT between the brain stem and choroid plexus. The
      anteroposterior diameter of IT in each case was measured. The relationship
      between IT with the other parameter was also examined. RESULTS: The IT at first
      trimester ranged from 1.35 to 2.6 mm. There was no significant association
      between IT with NT, and serum biochemistry. The intraobserver and interobserver
      agreement was assessed in 20 (19.6%) normal cases. Mean (SD) differences of two
      observers was -0.015 (0.132) mm (p > 0.05). For each observer, mean (SD) between
      the 2 paired measurements were -0.001 (0.097) mm, and 0.010 (0.085) mm,
      respectively (p > 0.05). CONCLUSIONS: In the first trimester, the reference range
      of IT in Chinese fetuses has been established. The assessment of IT is feasible
      and reproducible.

PMID- 21867406
TI  - Development and prevention of morphologic and ultrastructural changes in uremia
      induced hyperplastic parathyroid gland.
AB  - The detailed ultrastructural changes of uremia-induced hyperplastic parathyroid
      gland and the effects of current medical treatments for secondary
      hyperparathyroidism were investigated. Marked enlargement of parathyroid cell
      with accumulation of mitochondria and lipids and a significant increase in the
      thickness of the pericapillary area with increased fibrosis and appearance of
      fibroblast like cells were noted in the hyperplastic gland caused by uremia and
      phosphate retention. These ultrastructural changes and biochemical findings
      indicating hyperparathyroidism were significantly suppressed by all of the
      treatment using phosphate restriction, calcitriol, and cinacalcet. The
      characteristic ultrastructural changes, including the morphologic evidence of
      nodule formation, were indicated.

PMID- 21867407
TI  - Ultrastructure of the H. pylori microbe in individuals having macrocytosis and
      B12 deficiency.
AB  - The incidence of Helicobacter pylori gastritis is high in India and the number of
      individuals with vitamin B12 deficiency is also large. An association has been
      found between these two factors. It is necessary to determine whether H. pylori
      infection may be a factor in the causation of B12 deficiency and whether it is
      associated with any morphological changes on ultrastructural examination. A
      cohort-based study has been performed, which includes 505 young asymptomatic
      males. These cases have been investigated for presence of H. pylori and
      macrocytosis. The study confirms an association between H. pylori infection and
      B12 deficiency. It is recommended that H. pylori infection be looked for in
      subjects having macrocytosis of unknown etiology.

PMID- 21867408
TI  - Profile of T cell recognition of HIV type 1 consensus group M Gag and Nef
      peptides in a clade A1- and D-infected Ugandan population.
AB  - Reagents for evaluating non-clade B HIV-specific T cell responses are uncommon.
      Peptides based on highly conserved HIV-1 consensus group M sequences that are
      phylogenetically closer to most circulating strains may provide potential
      alternative reagents in populations with diverse infections, and may be relevant
      for vaccine design. Recognition of such reagents in clade A1-and D-infected
      populations has not been previously evaluated. Interferon (IFN)-gamma ELISpot
      assay was used to evaluate T cell recognition of Gag and Nef peptides based on
      consensus group M sequences in 50 treatment-naive adults predominantly infected
      with HIV-1 clades A1 and D. Gag-induced T cell responses were correlated with gag
      sequence diversity. Infecting clades were determined from gag sequences for 45 of
      the 50 subjects as 40% clade A1 (18/45), 45% clade D (20/45), 2% clade C (1/45),
      2% A1/C recombinant (1/45), 2% A1/D (1/45), 7% CRF10_CD (3/45), and 2% U
      (unclassifiable) (1/45). The mean genetic divergence and diversity of clade A and
      D gag region compared to group M consensus sequences at synonymous and
      nonsynonymous nucleotide and amino acid levels were not always significant. Gag
      peptides were targeted at significantly higher frequency [88% (44/50)] than Nef
      [64% (32/50)]; p=0.014, although their mean IFN-gamma magnitudes were comparable
      ([3703 (95% CI 2567-4839)] vs. [2120 (95% CI 478-3762)]), respectively.
      Measurable virus-induced IFN-gamma responses were detected in 96% (48/50)
      individuals, primarily targeting the more conserved Gag p24 and Nef central core
      regions. Use of these reagents to screen for HIV-specific IFN-gamma responses may
      mitigate the challenge of viral diversity; although this targeting is apparently
      biased toward a few highly conserved epitopes.

PMID- 21867410
TI  - Glutathione peroxidases in Lolium multiflorum and Festuca arundinacea: Activity,
      susceptibility to herbicides and characteristics.
AB  - To evidence a possible mechanism of defense toward oxidative stress induced by
      herbicides in plants, an investigation was carried on the activity of glutathione
      peroxidase (GPX) in Italian ryegrass (Lolium multiflorum) and in Festuca (Festuca
      arundinacea) in response to atrazine (6-chloro-N-ethyl-N'-isopropyl-1,3,5
      triazine-2,4-diamine) and fluorodifen (4-nitrophenyl alpha,alpha,alpha-trifluoro
      2-nitro-p-tolyl ether). In general, the herbicide treatments significantly
      induced GPX activity in the shoots of Italian ryegrass, whereas inhibited it in
      Festuca. These opposite behaviors are examined, taking into account the
      accumulation and persistence of the two herbicides in the plants, and they are
      discussed in terms of GPX counteraction to oxidative stress in the first case,
      and of a lower detoxification rate unable to prevent a deleterious effect on the
      GPX activity in the second case. Further information on the properties of Italian
      ryegrass and Festuca GPX were achieved by purification and isolation of the
      enzymes, performed by protein liquid chromatography and by electrophoretic
      analyses. GPX of both the plants were found to be heterodimer with multiple
      function in showing also glutathione S-transferase (GST) activity.

PMID- 21867411
TI  - Development and validation of the HOPE prognostic index on 24-month posthospital
      mortality and rehospitalization: Italian National Research Center on Aging
      (INRCA).
AB  - BACKGROUND: A fast and simple tool is needed to test for the risk of mortality
      and rehospitalization in older patients. OBJECTIVE: The aim of this study was to
      construct and validate a prognostic index using specific items from the
      Comprehensive Geriatric Assessment (CGA) in a large population of older
      hospitalized adults. METHOD: This was a prospective study of a 24-month follow-up
      period, between 2005 to 2008 in 3,043 elderly patients (mean age, 81 +/- 6)
      discharged from three acute geriatric wards in the Marche region of Italy.
      Baseline predictors of demographics and 25 items from the CGA regarding
      functional and cognitive status, depression, co-morbidity, social isolation, and
      quality of life were used to build a summary score, the Hospitalized Older
      Patient Examination (HOPE) Index. The HOPE index was developed in 1,533 patients
      and validated in 1,510 consecutively hospitalized patients. Outcome measures were
      24-month mortality and rehospitalization. RESULTS: Three risk categories of HOPE
      based on the best sensitivity and specificity for mortality and rehospitalization
      were: Low (<=4), moderate (4-8), and high (>=8). Categorizing data across the
      HOPE index, mortality ranged from 7.9% to 14.5% in the development cohort and
      6.2% to 14.0% in the validation cohort, whereas rehospitalization ranged from
      68.3% to 79.4% and 69.8% to 79.8%, respectively. Kaplan-Meier survival curves
      demonstrated that risk for mortality increased with a worsening across the HOPE
      index (p < 0.001). In the development and validation cohorts, a close agreement
      was found for HOPE on mortality and rehospitalization with a receiver operating
      characteristic (ROC) of 0.69 (95% confidence interval [CI] 0.61-0.74) vs. 0.67
      (95% CI 0.57-0.70) and rehospitalization of 0.62 (95% CI 0.58-0.66) vs. 0.60 (95%
      CI 0.56-0.63), respectively. In the development and validation cohorts, Cox
      proportional hazard models showed that a high HOPE index predicted risks of 2.38
      (1.34-4.23) and 2.86 (1.24-6.61) on mortality and 1.27 (1.09-1.44) and 1.37 (1.10
      1.64) on rehospitalization, respectively. CONCLUSIONS: HOPE may be useful for
      long-term clinical planning, discharge, and follow-up.

PMID- 21867413
TI  - Enzyme-linked immunosorbent assay and polymerase chain reaction performance using
      Mexican and Guatemalan discrete typing unit I strains of Trypanosoma cruzi.
AB  - Thirteen Trypanosoma cruzi isolates from different geographic regions of Mexico
      and Guatemala belonging to discrete typing unit (DTU) I and a reference CL-Brener
      (DTU VI) strain were used to perform enzyme-linked immunosorbent assay (ELISA)
      and polymerase chain reaction (PCR). A panel of 57 Mexican serum samples of
      patients with chronic chagasic cardiopathy and asymptomatic infected subjects
      (blood bank donors) were used in this study. DNA from the above 14 T. cruzi
      strains were extracted and analyzed by PCR using different sets of primers
      designed from minicircle and satellite T. cruzi DNA. The chronic chagasic
      cardiopathy serum samples were easily recognized with ELISA regardless of the
      source of antigenic extract used, even with the CL-Brener TcVI, but positive
      serum samples from blood bank donors in some cases were not recognized by some
      Mexican antigenic extracts. On the other hand, PCR showed an excellent
      performance despite the set of primers used, since all Mexican and Guatemalan T.
      cruzi strains were correctly amplified. In general terms, Mexican, Guatemalan,
      and CL-Brener T. cruzi strains are equally good sources of antigen when using the
      ELISA test to detect Mexican serum samples. However, there are some strains with
      poor performance. The DTU I strains are easily detected using either kinetoplast
      or satellite DNA target designed from DTU VI strains.

PMID- 21867412
TI  - Combined exercise and insulin-like growth factor-1 supplementation induces
      neurogenesis in old rats, but do not attenuate age-associated DNA damage.
AB  - We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF
      1) supplementation (5 MUg/kg per day) and 6 weeks of exercise training (60% of
      the maximal oxygen consumption [VO2 max]) on neurogenesis, DNA damage/repair, and
      sirtuin content in the hippocampus of young (3 months old) and old (26 months
      old) rats. Exercise improved the spatial memory of the old group, but IGF-1
      supplementation eliminated this effect. An age-associated decrease in
      neurogenesis was attenuated by exercise and IGF-1 treatment. Aging increased the
      levels of 8-oxo-7,8-dihydroguanine (8-oxoG) and the protein Ku70, indicating the
      role of DNA damage in age-related neuropathology. Acetylation of 8-oxoguanine DNA
      glycosylase (OGG1) was detected in vivo, and this decreased with aging. However,
      in young animals, exercise and IGF-1 treatment increased acetylated (ac) OGG1
      levels. Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine
      deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large
      increase in acetylated lysine residues in the hippocampus. On the other hand,
      SIRT3 increased with aging. Exercise-induced neurogenesis might not be a
      causative factor of increased spatial memory, because IGF-1 plus exercise can
      induce neurogenesis in the hippocampus of older rats. Data revealed that the age
      associated increase in 8-oxoG levels is due to decreased acetylation of OGG1. Age
      associated decreases in SIRT1 and the associated increase in lysine acetylation,
      in the hippocampus, could have significant impact on function and thus, could
      suggest a therapeutic target.

PMID- 21867414
TI  - First report of natural infection of least weasel (Mustela nivalis Linnaeus,
      1776) with Leishmania major in Tunisia.
AB  - Zoonotic cutaneous leishmaniasis, caused by Leishmania major (L. major), is
      endemic in Tunisia. Several rodents have been identified as reservoir hosts of
      parasites. This study reports, for the first time, the natural infection with L.
      major zymodeme MON-25 in a specimen of least weasel: Mustela nivalis Linnaeus,
      1776 (M. nivalis) collected in Sidi Bouzid. This finding justifies further
      research on larger samples of this animal to verify its role as a potential
      reservoir host for cutaneous leishmaniasis in Tunisia.

PMID- 21867415
TI  - Commerson's leaf-nosed bat (Hipposideros commersoni) is the likely reservoir of
      Shimoni bat virus.
AB  - In this study we attempted to identify whether Commerson's leaf-nosed bat
      (Hipposideros commersoni) is the reservoir of Shimoni bat virus (SHIBV), which
      was isolated from a bat of this species in 2009. An alternative explanation is
      that the isolation of SHIBV from H. commersoni was a result of spill-over
      infection from other species, particularly from the Egyptian fruit bats
      (Rousettus aegyptiacus), which frequently sympatrically roost with H. commersoni
      and are known as the reservoir of the phylogenetically related Lagos bat virus
      (LBV). To evaluate these hypotheses, 769 bats of at least 17 species were sampled
      from 18 locations across Kenya during 2009?2010. Serum samples were subjected to
      virus neutralization tests against SHIBV and LBV. A limited amount of cross
      neutralization between LBV and SHIBV was detected. However, H. commersoni bats
      demonstrated greater seroprevalence to SHIBV than to LBV, and greater virus
      neutralizing titers to SHIBV than to LBV, with a mean difference of 1.16 log(10)
      (95% confidence intervals [CI]: 0.94-1.40; p<0.001). The opposite pattern was
      observed for sera of R. aegyptiacus bats, with a mean titer difference of 1.06
      log(10) (95% CI: 0.83-1.30; p<0.001). Moreover, the seroprevalence in H.
      commersoni to SHIBV in the cave where these bats sympatrically roosted with R.
      aegyptiacus (and where SHIBV was isolated in 2009) was similar to their
      seroprevalence to SHIBV in a distant cave where no R. aegyptiacus were present
      (18.9% and 25.0%, respectively). These findings suggest that H. commersoni is the
      host species of SHIBV. Additional surveillance is needed to better understand the
      ecology of this virus and the potential risks of infection to humans and other
      mammalian species.

PMID- 21867409
TI  - The human paraoxonase gene cluster as a target in the treatment of
      atherosclerosis.
AB  - The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1,
      PON2, and PON3. Originating from the same fungus lactonase precursor, all of the
      three PON genes share high sequence identity and a similar beta propeller protein
      structure. PON1 and PON3 are primarily expressed in the liver and secreted into
      the serum upon expression, whereas PON2 is ubiquitously expressed and remains
      inside the cell. Each PON member has high catalytic activity toward corresponding
      artificial organophosphate, and all exhibit activities to lactones. Therefore,
      all three members of the family are regarded as lactonases. Under physiological
      conditions, they act to degrade metabolites of polyunsaturated fatty acids and
      homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both
      oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against
      atherosclerosis and coronary artery diseases, as has been illustrated by many
      types of in vitro and in vivo experimental evidence. Clinical observations
      focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are
      protective against coronary artery disease. Many other conditions, such as
      diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The
      abundance and/or activity of PONs can be regulated by lipoproteins and their
      metabolites, biological macromolecules, pharmacological treatments, dietary
      factors, and lifestyle. In conclusion, both previous results and ongoing studies
      provide evidence, making the PON cluster a prospective target for the treatment
      of atherosclerosis.

PMID- 21867416
TI  - Distribution of mosquitoes and mosquito-borne arboviruses in Inner Mongolia,
      China.
AB  - During summers in 2007 and 2008, an investigation was conducted to identify the
      distribution of mosquitoes and circulation of mosquito-borne arboviruses in Inner
      Mongolia, China. A total of 10,542 mosquitoes consisting of seven species from
      the Aedes, Culex, and Anopheles genera were trapped by UV-light traps, and they
      were sorted into 211 pools according to species, location, and date of
      collection. The result showed that Aedes dorsalis was the most common species,
      accounting for 41.0% (4327/10,542) of the total. Culex modestus (17.1%,
      1801/10,542) made up the second largest species, followed by Aedes flavidorsalis
      (16.3%, 1714/10,542). Six virus isolates were obtained from pooled mosquitoes
      using cell culture and were identified as Tahyna virus (two isolates from Ae.
      dorsalis and C. modestus), Banna virus (one isolate from C. modestus), and Culex
      Pipiens pallens Densovirus (three isolates from Aedes caspius) by serological and
      molecular methods.

PMID- 21867417
TI  - Larval nutritional stress does not affect vector competence for West Nile virus
      (WNV) in Culex tarsalis.
AB  - In some mosquito species the conditions experienced by larvae during development
      have been shown to lead to changes in susceptibility to various arboviruses in
      the adult female. Since laboratory mosquitoes are generally reared under ideal
      conditions, mosquito vector competence experiments in the laboratory may not
      accurately reflect vector?virus relationships in nature. We examined the
      consequences of larval nutritional stress on Culex tarsalis vector competence for
      West Nile virus (WNV). Larval nutrition deprivation resulted in increased
      development time, decreased pupation and emergence rates, and smaller adult
      female body size. However, infection, dissemination, and transmission rates for
      WNV at 5, 7, and 14 days postfeeding were not consistently affected. These
      results suggest that larval nutritional rearing protocols are not a major factor
      in laboratory estimates of WNV vector competence in Cx. tarsalis.

PMID- 21867418
TI  - Seroprevalence of West Nile virus-specific antibodies in a cohort of blood donors
      in northeastern Italy.
AB  - IgG and IgM levels against West Nile virus (WNV) were measured in 20,033 serum
      samples that were obtained between October 2008 to September 2009 from 9913 blood
      donors in the district of Ferrara, northeastern Italy. As confirmatory test, a
      microneutralization assay was used to detect the presence of neutralizing
      antibodies against WNV. Sixty-eight subjects (0.69%) were positive for anti-WNV
      by immunofluorescence assay. Large differences in the prevalence of antibodies to
      WNV were noted between towns in the area evaluated.

PMID- 21867419
TI  - Virulence of pathogenic Coxiella burnetii strains after growth in the absence of
      host cells.
AB  - Coxiella burnetii is a gram-negative bacterium that causes the zoonotic disease Q
      fever. Traditionally considered an obligate intracellular agent, the requirement
      to be grown in tissue culture cells, embryonated eggs, or animal hosts has made
      it difficult to isolate strains and perform genetic studies on C. burnetii.
      However, it was recently demonstrated that the attenuated Nine Mile Phase 2 (NM2)
      C. burnetii strain will grow axenically in acidified citrate cysteine medium
      (ACCM) in a 2.5% oxygen environment. The current study was undertaken to
      determine whether more virulent C. burnetii strains could be grown in ACCM, and
      whether virulence would be maintained after passage. The ACCM medium supported an
      ?1000-fold expansion of Nine Mile Phase 1 (NM1), NM2, M44, and Henzerling strains
      of C. burnetii, whereas the Priscilla (Q177) strain expanded only 100-fold, and
      the K strain (Q154) grew poorly in ACCM. To determine if passage in ACCM would
      maintain the virulence of C. burnetii, the NM1 strain was grown for up to 26
      weekly passages in ACCM. C. burnetii maintained in ACCM for 5 or 8 passages
      maintained full virulence in a mouse model, but NM1 passaged for 23 or 26 times
      was somewhat attenuated. These data demonstrate that virulent strains of C.
      burnetii can be successfully passaged in ACCM; however, some strains can lose
      virulence after extended passage, and other strains grow poorly in this medium.
      The loss of virulence in axenic culture was associated with some truncation of
      lipopolysaccharide chains, suggesting a possible mechanism for attenuation.

PMID- 21867420
TI  - Agents of human anaplasmosis and Lyme disease at Camp Ripley, Minnesota.
AB  - The transmission dynamics of Anaplasma phagocytophilum (Ap) and Borrelia
      burgdorferi (Bb) among Ixodes scapularis (Is) and mammalian hosts was
      investigated at Camp Ripley, an area representative of central Minnesota.
      Prevalence of white-footed mouse infection with Ap and Bb were 20% and 42%,
      respectively, with a coinfection level of 14%. Peak levels of infection with both
      agents occurred in May. The average levels of seropositivity to Ap and Bb were
      29.3% and 48%, respectively. Of the mice infected with Ap, 47.5% were able to
      eliminate the pathogen as compared with 19.4% of mice infected with Bb. Ap was
      detected in 88.4% of 43 eastern chipmunks examined and isolated from 44.7% of the
      animals. Bb was present in 72.7% of 11 chipmunks examined, and 100% of the
      animals were also infected with Ap. The seasonality of tick activity differs from
      that reported for the New York area. Is infestation of mice began in May with
      peak nymphal infestation also occurring in May (7.4 per infested mouse) and
      overlapping with peak larval infestation in June (77.1 per infested mouse).
      Infestation ranged from 100% in May to 34.5% in October. Is comprised 98.4% of
      the ticks infesting the mice. The temporal pattern of the developmental stages of
      Is infesting chipmunks was the same as for mice, except that the tick burdens
      were greater. The nymphal stage peaked in May (81.3 per animal), and the larval
      stage peaked in June (164.7 per animal). Infestation was 100% in May-August, and
      >99% of the ticks were Is. Antibodies to Ap were present in >80% of the white
      tailed deer examined, but they were infected with the Ap-1 variant rather than
      the Ap strain infecting mice and humans. Antibodies to Bb were detected in >80%
      of the deer, but Bb DNA was only detected in 1.5% of blood specimens.

PMID- 21867421
TI  - High rates of Rickettsia parkeri infection in Gulf Coast ticks (Amblyomma
      maculatum) and identification of "Candidatus Rickettsia andeanae" from Fairfax
      County, Virginia.
AB  - The Gulf Coast tick, Amblyomma maculatum, is a vector of Rickettsia parkeri, a
      recently identified human pathogen that causes a disease with clinical symptoms
      that resemble a mild form of Rocky Mountain spotted fever. Because the prevalence
      of R. parkeri infection in geographically distinct populations of A. maculatum is
      not fully understood, A. maculatum specimens collected as part of a tick and
      pathogen surveillance system in Fairfax County, Virginia, were screened to
      determine pathogen infection rates. Overall, R. parkeri was found in 41.4% of the
      A. maculatum that were screened. Additionally, the novel spotted fever group
      Rickettsia sp., tentatively named "Candidatus Rickettsia andeanae," was observed
      for the first time in Virginia.

PMID- 21867422
TI  - Molecular diagnostics of Rickettsia africae infection in travelers returning from
      South Africa to The Netherlands.
AB  - BACKGROUND: African tick-bite fever (ATBF) is frequently diagnosed in The
      Netherlands in travelers returning from South Africa. It is caused by Rickettsia
      africae and diagnosis is based on travel history and clinical presentation and
      usually confirmed by detecting serum antibodies against rickettsiae of the
      spotted fever group. However, these typically occur late in the course of the
      disease, and a mild clinical course or early antibiotic treatment can diminish
      antibody production. METHODS AND RESULTS: Four travelers presented with
      (sub)febrile temperatures and eschar(s), several days after returning from South
      Africa. R. africae DNA was amplified and sequenced from skin biopsies of the
      eschars of all patients. Initial immunofluorescence assays yielded no
      immunoglobulin M (IgM)/IgG antibodies directed against spotted fever group
      rickettsiae; however, serology in the convalescent phase-several weeks after the
      patients had fully recovered-was positive. CONCLUSIONS: ATBF should be considered
      in travelers returning from South Africa to The Netherlands with febrile illness
      and (multiple) skin lesions. The diagnosis can be confirmed by (paired) serology;
      however, polymerase chain reaction and sequencing on skin biopsies could be a
      (faster and more accurate) confirmatory test. Advantages of molecular methods
      over serology are species identification and high sensitivity early in the course
      of the disease.

PMID- 21867423
TI  - Target-mediated metabolism and target-mediated drug disposition of the DPPIV
      inhibitor AMG 222.
AB  - Pharmacokinetic and metabolism aspects of AMG 222 interaction with target enzyme,
      dipeptidylpeptidase IV (DPPIV) were investigated. Inhibition of recombinant human
      DPPIV by AMG 222 was measured. IC(50) decreased as preincubation time increased.
      k(off), k(on) and K(d) were measured. Dilution assay indicated a long
      dissociation half-life (730 min) relative to DPPIV inhibitor vildagliptin. AMG
      222 is a slow-on, tight-binding, slowly reversible inhibitor of DPPIV. Amide and
      acid metabolites arising from hydrolysis of AMG 222's cyano group were formed
      slowly by rhDPPIV, but not by microsomes or S9. The amide metabolite was
      converted to the acid metabolite by rhDPPIV, but not by an active site mutant.
      These metabolites of AMG 222 are formed by target-mediated metabolism of the
      cyano group, similar to vildagliptin. Human plasma protein binding of [(14)C]AMG
      222 was saturable and concentration-dependent. After 30 min, [(14)C]AMG 222 was
      80.8% bound at 1 nM and binding decreased to 29.4% above 100 nM. The plasma DPPIV
      concentration (4.1 nM) and human plasma AMG 222 concentrations that inhibit
      DPPIV, occurred in the range of concentration-dependent binding. Target-mediated
      drug disposition influences AMG 222 pharmacokinetics, similar to DPPIV inhibitor,
      linagliptin.

PMID- 21867424
TI  - Human neural progenitor cells show functional neuronal differentiation and
      regional preference after engraftment onto hippocampal slice cultures.
AB  - The transplantation of stem cells offers potential therapies for many
      neurodegenerative disorders that currently have limited or no treatment options.
      However, relatively little is known about how the host environment affects the
      development and integration of these cells. In this study we have engrafted
      immortalized human midbrain neural progenitor cells (NPCs) onto rat hippocampal
      brain slice cultures to examine the influence of a neural environment on
      differentiation. Patch clamp recordings revealed that the transplanted progenitor
      cells could express neuronal-type voltage-gated currents and rapidly receive
      synaptic input from the hippocampal brain slice. The distribution of progenitor
      cells across the hippocampal slices was strongly influenced by the neural
      architecture, with most cells located in the fissural regions and sending
      processes parallel to the laminar structure, while in contrast, cells located in
      the dentate gyrus showed no organized pattern. Almost no cells were found in the
      stratum radiatum or pyramidal cell layers. Together, these results demonstrate
      the potential for the architecture of the host environment to regulate the
      integration of transplanted cells, and highlight the utility of coculture systems
      for studying the mechanisms underlying the migration, integration, and
      differentiation of human NPCs in structured neural environments.

PMID- 21867425
TI  - Bone marrow microenvironment in an in vitro model of Gaucher disease:
      consequences of glucocerebrosidase deficiency.
AB  - Gaucher disease (GD) is a lysosomal storage disorder due to glucocerebrosidase
      (GBA) deficiency. Mechanisms leading to the emergence of hematological and
      skeletal manifestations observed in GD are poorly explained. Bone marrow (BM)
      mesenchymal stem cells (MSCs) are multipotent progenitors that participate in the
      regulation of bone mass. MSCs should thus represent a cell population involved in
      the development or progression of bone disease in GD. In a chemical model of GD
      obtained with Conduritol beta epoxide (CBE), a specific inhibitor of GBA
      activity, we functionally characterized BM MSCs and specifically analyzed their
      capacity to differentiate into osteoblasts. GBA deficiency obtained with CBE
      treatment, leads to a dramatic impairment of MSCs proliferation and to
      morphological abnormalities. Although the capacity of MSCs to differentiate into
      osteoblasts was not modified, the levels of several soluble factors that regulate
      bone metabolism were increased in MSCs treated with CBE, compared with untreated
      MSCs. Moreover, addition of conditioned media from CBE-treated MSCs on monocyte
      derived osteoclasts cultured on bone matrix leads to an increase of resorption
      areas. These data suggested that, in GD, MSCs represents a stem cell population
      that is likely to be involved in bone pathogenesis.

PMID- 21867427
TI  - Xeno-free plant-derived hydrolysate-based freezing of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are one of the most interesting cell types for
      tissue engineering and cell therapy. The large-scale banking of hESCs for
      research and future clinical application requires economic, defined, and xeno
      free cryopreservation protocols. In this study, the possibility to substitute
      knockout serum replacement (KO-SR) in the cryopreservation process with vegetal
      and synthetic hydrolysates was investigated. To our knowledge, the use of
      hydrolysates in hESC cryopreservation has not been yet explored. Initially, 3
      different hydrolysates (Ultrapep Soy, Hypep 4601 and EX-CELL((r)) CD Hydrolysate
      Fusion) were tested in the cryopreservation solution. A concentration of 8 mg/mL
      EX-CELL CD Hydrolysate Fusion in the cryopreservation solution leads to the
      highest recovery ratio; thus, this solution was selected for additional
      cryopreservation experiments. To ensure reproducibility of the results, 3 hESC
      lines (HS181, H9, and BG01) were used. The hESCs were collected prefreezing by
      application of collagenase IV and cell dissociation solution. Experiments showed
      that it was feasible to substitute the KO-SR in both the cryopreservation
      solution as the thawing solution. The obtained recovery ratios were comparable to
      those obtained with KO-SR (no statistical significant difference; Student's t
      test, P<0.05). Further optimization protocols showed a doubling of the obtained
      recovery ratio after addition of Rock-inhibitor Y-27632 post-thawing. The
      expansion profile and pluripotency analysis revealed no changes in normal hESC
      behavior. We conclude that the application of vegetal or synthetic hydrolysates
      is suitable for xeno-free hESC cryopreservation.

PMID- 21867426
TI  - Human adipose-derived stem cells impair natural killer cell function and exhibit
      low susceptibility to natural killer-mediated lysis.
AB  - Human adipose-derived stem cells (hASCs) have been successfully used in treating
      numerous diseases. However, several aspects need to be considered, particularly
      in the context of allogeneic cell therapy. To better understand hASCs-host
      interactions, we studied the phenotype of hASCs and their modulatory effect on
      natural killer (NK) cells by using bone marrow-mesenchymal stem cells (hBM-MSCs)
      as a reference. The hASCs displayed a lower susceptibility to NK cell-mediated
      lysis and a lower expression of ligands for DNAM-1 when compared with hBM-MSCs.
      Moreover, here we demonstrated that hASCs and hBM-MSCs can modulate NK cells
      through the action of soluble factors such as indoleamine 2,3-dioxygenase.
      Altogether, these results suggest that for an adoptive cell therapy based on the
      transfer of allogeneic hASCs, the NK-hASCs crosstalk will not result in an
      immediate recognition of the transferred cells. Thus, hASCs may remain in the
      tissue long enough to balance the immune response before being cleared.

PMID- 21867428
TI  - Radiation Resistance in Cancer Therapy: meeting summary and research
      opportunities. Report of an NCI Workshop held September 1-3, 2010.

PMID- 21867429
TI  - Using genetically engineered mice for radiation research.
AB  - The laboratory mouse has been used for many decades as a model system for
      radiation research. Recent advances in genetic engineering now allow scientists
      to delete genes in specific cell types at different stages of development. The
      ability to manipulate genes in the mouse with spatial and temporal control opens
      new opportunities to investigate the role of genes in regulating the response of
      normal tissues and tumors to radiation. Currently, we are using the Cre-loxP
      system to delete genes, such as p53, in a cell-type specific manner in mice to
      study mechanisms of acute radiation injury and late effects of radiation. Our
      results demonstrate that p53 is required in the gastrointestinal (GI) epithelium
      to prevent radiation-induced GI syndrome and in endothelial and/or hematopoietic
      cells to prevent late effects of radiation. We have also used these genetic tools
      to generate primary tumors in mice to study tumor response to radiation therapy.
      These advances in genetic engineering provide a powerful model system to dissect
      both the mechanisms of normal tissue injury after irradiation and the mechanisms
      by which radiation cures cancer.

PMID- 21867430
TI  - Dietary selenium for the mitigation of radiation injury: effects of selenium dose
      escalation and timing of supplementation.
AB  - We recently reported that daily dietary supplementation with 100 ug selenium (a
      dose exceeding a rat's nutritional requirement by about 33-fold) initiated
      immediately after total-body irradiation (TBI) and maintained for 21 weeks
      mitigates radiation nephropathy in a rat model as indicated by blood urea
      nitrogen (BUN) levels and histopathological criteria (Radiat Res. 2009; 17:368
      73). In this follow-up study, we explored the risks and benefits of delaying the
      onset of supplementation, shortening periods of supplementation, and escalating
      selenium supplementation beyond 100 ug/day. Supplementation with 200 ug
      selenium/day (as selenite or seleno-l-methionine) substantially improved the
      mitigation of radiation nephropathy by lowering BUN levels at 4 months after TBI
      from 115 to as low as 34 mg/dl and by proportionally lowering the incidence of
      histopathological abnormalities. Shortening the period of supplementation to 3 or
      2 months did not compromise efficacy. Delaying the onset of supplementation for 1
      week reduced but did not abrogate the mitigation of radiation nephropathy.
      Supplementation with 300 ug/day mitigated radiation nephropathy less effectively
      than 200 ug and was poorly tolerated. Rats that had been given 10 Gy of TBI were
      less tolerant of high-dose selenium than nonirradiated rats. This reduced
      tolerance of high-dose selenium would need to be taken into consideration when
      selenium is used for the mitigation of radiation injury in victims of nuclear
      accidents or acts of radiological terrorism. The high dose requirements, the
      pronounced threshold effect, and the superior performance of selenite suggest
      that the mitigation of radiation nephropathy involves mechanisms that go beyond
      the induction of selenoproteins.

PMID- 21867431
TI  - New translational possibilities for microenvironmental modulation of
      radiosensitivity.

PMID- 21867432
TI  - Mini-implants vs fixed functional appliances for treatment of young adult Class
      II female patients: a prospective clinical trial.
AB  - OBJECTIVE: To compare the treatment effects of maxillary anterior teeth
      retraction with mini-implant anchorage in young adults with Class II division 1
      malocclusion undergoing extraction of the maxillary first premolars with similar
      patients treated by a fixed functional appliance. MATERIALS AND METHODS: Thirty
      four young adult female patients (mean age 16.5 +/- 3.2 years, overjet >= 6 mm)
      with a Class II division 1 malocclusion were divided into two groups: group 1
      (G1), in which overjet correction was obtained with a fixed functional appliance
      (FFA), and group 2 (G2), in which upper first premolars were extracted, followed
      by space closure with MIs as anchor units. Dentoskeletal and soft tissue changes
      were analyzed on lateral cephalograms taken before (T1) and after (T2) correction
      of the overjet. RESULTS: Both methods were useful in improving the overjet and
      interincisal relationships. Extrusion and mesial movement of the lower molar,
      together with lower incisor proclination, were noted in G1. G2 showed
      distalization and intrusion of the upper molar. The nasio-labial angle became
      more obtuse in G2, while lower lip protrusion was seen for G1. CONCLUSIONS: The
      two treatment protocols provided adequate dental compensation for the Class II
      malocclusion, but did not correct the skeletal discrepancy. There were
      significant differences in the dental and soft tissue treatment effects between
      the two treatment protocols.

PMID- 21867433
TI  - Evolutionary reduction of the first thoracic limb in butterflies.
AB  - Members of the diverse butterfly families Nymphalidae (brush-footed butterflies)
      and Riodinidae (metalmarks) have reduced first thoracic limbs and only use two
      pairs of legs for walking. In order to address questions about the detailed
      morphology and evolutionary origins of these reduced limbs, the three thoracic
      limbs of 13 species of butterflies representing all six butterfly families were
      examined and measured, and ancestral limb sizes were reconstructed for males and
      females separately. Differences in limb size across butterflies involve changes
      in limb segment size rather than number of limb segments. Reduction of the first
      limb in both nymphalids and riodinids appears particularly extensive in the
      femur, but the evolution of these reduced limbs is suggested to be a convergent
      evolutionary event. Possible developmental differences as well as ecological
      factors driving the evolution of reduced limbs are discussed.

PMID- 21867434
TI  - Reproductive behavior and fitness components in male Drosophila melaogaster are
      non-linearly affected by the number of male co-inhabitants early in adult life.
AB  - Although multiple lines of evidence suggest that early adult life is very
      important in shaping the reproductive behavior of males, few studies have looked
      at the fitness consequences of the variation in reproductive behavior induced by
      differences in early life experience of males. Using a long term laboratory
      adapted population of Drosophila melanogaster Meigen (Diptera: Drosophilidae),
      early life experience, in terms of co-inhabitant numbers, was found to affect
      male mating behavior and at least one fitness component. However, in contrast to
      previous studies, a non-linear relationship was found between early life
      experience and fitness components and a significant effect of co-inhabitant
      number on copulation duration and sperm defense. Both these traits showed a sharp
      increase as the co-inhabitant numbers changed from 1 to 16. However, there was a
      decline in the trait values as the co-inhabitant number increased further. The
      probable causes for the observed non-linear pattern of responses are discussed.

PMID- 21867435
TI  - Laboratory studies of feeding and oviposition preference, developmental
      performance, and survival of the predatory beetle, Sasajiscymnus tsugae on diets
      of the woolly adelgids, Adelges tsugae and Adelges piceae.
AB  - The suitability of the balsam woolly adelgid, Adelges piceae Ratzeburg
      (Hemiptera: Adelgidae) as an alternate mass rearing host for the adelgid
      predator, Sasajiscymnus tsugae Sasaji and McClure (Coleoptera: Coccinellidae) was
      studied in the laboratory. This predator is native to Japan and has been
      introduced to eastern hemlock, Tsuga canadensis (L.) Carriere (Pinales:
      Pinaceae), forests throughout the eastern United States for biological control of
      the hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), also of
      Japanese origin. Feeding, oviposition, immature development, and adult long-term
      survival of S. tsugae were tested in a series of no choice (single-prey) and
      paired-choice experiments between the primary host prey, A. tsugae, and the
      alternate host prey, A. piceae. In paired-choice feeding tests, the predator did
      not discriminate between eggs of the two adelgid species, but in the no choice
      tests the predator did eat significantly more eggs of A. piceae than those of A.
      tsugae. S. tsugae accepted both test prey for oviposition and preferred to lay
      eggs on adelgid infested versus noninfested host plants. Overall oviposition
      rates were very low (< 1 egg per predator female) in the oviposition preference
      tests. Predator immature development rates did not differ between the two test
      prey, but only 60% of S. tsugae survived egg to adult development when fed A.
      piceae compared to 86% when fed A. tsugae. S. tsugae adult long-term survival was
      significantly influenced (positively and negatively) by prey type and the
      availability of a supplemental food source (diluted honey) when offered
      aestivating A. tsugae sistens nymphs or ovipositing aestivosistens A. piceae
      adults, but not when offered ovipositing A. tsugae sistens adults. These results
      suggest that the development of S. tsugae laboratory colonies reared on a diet
      consisting only of A. piceae may be possible, and that the biological control
      potential of the predator might be expanded to include management of A. piceae in
      Christmas tree plantations.

PMID- 21867436
TI  - Variation in morphological characters of two invasive leafminers, Liriomyza
      huidobrensis and L. sativae, across a tropical elevation gradient.
AB  - Changes in morphological traits along elevation and latitudinal gradients in
      ectotherms are often interpreted in terms of the temperature-size rule, which
      states that the body size of organisms increases under low temperatures, and is
      therefore expected to increase with elevation and latitude. However other factors
      like host plant might contribute to spatial patterns in size as well,
      particularly for polyphagous insects. Here elevation patterns for trait size and
      shape in two leafminer species are examined, Liriomyza huidobrensis (Blanchard)
      (Diptera: Agromyzidae) and L. sativae Blanchard, along a tropical elevation
      gradient in Java, Indonesia. Adult leafminers were trapped from different
      locations in the mountainous area of Dieng in the province of Central Java. To
      separate environmental versus genetic effects, L. huidobrensis originating from
      1378 m and 2129 m ASL were reared in the laboratory for five generations. Size
      variation along the elevation gradient was only found in L. huidobrensis and this
      followed expectations based on the temperature-size rule. There were also complex
      changes in wing shape along the gradient. Morphological differences were
      influenced by genetic and environmental effects. Findings are discussed within
      the context of adaptation to different elevations in the two species.

PMID- 21867437
TI  - First record of Fusarium verticillioides as an entomopathogenic fungus of
      grasshoppers.
AB  - Fusarium verticillioides (Saccardo) Nirenberg (Ascomycota: Hypocreales) is the
      most common fungus reported on infected corn kernels and vegetative tissues, but
      has not yet been documented as being entomopathogenic for grasshoppers.
      Grasshoppers and locusts represent a large group of insects that cause economic
      damage to forage and crops. Tropidacris collaris (Stoll) (Orthoptera: Acridoidea:
      Romaleidae) is a large and voracious grasshopper that in recent years has become
      an increasingly recurrent and widespread pest in progressively more greatly
      extended areas of some of in Argentina's northern provinces, with chemical
      insecticides being currently the only means of control. During February and March
      of 2008-09, nymphs and adults of T. collaris were collected with sweep nets in
      dense woodland vegetation at a site near Tres Estacas in western Chaco Province,
      Argentina, and kept in screened cages. F. verticillioides was isolated from
      insects that died within 10 days and was cultured in PGA medium. Pathogenicity
      tests were conducted and positive results recorded. Using traditional and
      molecular-biological methods, an isolate of F. verticillioides was obtained from
      T. collaris, and its pathogenecity in the laboratory was shown against another
      harmful grasshopper, Ronderosia bergi (Stal) (Acridoidea: Acrididae:
      Melanoplinae). The mortality caused by F. verticillioides on R. bergi reached 58
      +/- 6.53% by 10 days after inoculation. This is the first record of natural
      infection caused by F. verticillioides in grasshoppers.

PMID- 21867438
TI  - Characterization of polymorphic microsatellites in the giant bulldog ant,
      Myrmecia brevinoda and the jumper ant, M. pilosula.
AB  - The ant genus Myrmecia Fabricius (Hymenoptera: Formicidae) is endemic to
      Australia and New Caledonia, and has retained many biological traits that are
      considered to be basal in the family Formicidae. Here, a set of 16 dinucleotide
      microsatellite loci were studied that are polymorphic in at least one of the two
      species of the genus: the giant bulldog ant, M. brevinoda Forel, and the jumper
      ant, M. pilosula Smith; 13 are novel loci and 3 are loci previously published for
      the genus Nothomyrmecia Clark (Hymenoptera: Formicidae). In M. brevinoda, the
      total of 12 polymorphic microsatellites yielded a total of 125 alleles, ranging
      from 3 to 18 with an average of 10.42 per locus; the observed and expected
      heterozygosities ranged from 0.4000 to 0.9000 and from 0.5413 to 0.9200,
      respectively. In M. pilosula, the 9 polymorphic loci yielded a total of 67
      alleles, ranging from 3 to 12 with an average of 7.44 per locus; the observed and
      expected heterozygosities ranged from 0.5625 to 0.9375 and from 0.4863 to 0.8711,
      respectively. Five loci were polymorphic in both target species. In addition, 15
      out of the 16 loci were successfully amplified in M. pyriformis. These
      informative microsatellite loci provide a powerful tool for investigating the
      population and colony genetic structure of M. brevinoda and M. pilosula, and may
      also be applicable to a range of congeners considering the relatively distant
      phylogenetic relatedness between M. pilosula and the other two species within the
      genus Myrmecia.

PMID- 21867439
TI  - Carrion beetles visiting pig carcasses during early spring in urban, forest and
      agricultural biotopes of Western Europe.
AB  - Carrion beetles are important in terrestrial ecosystems, consuming dead mammals
      and promoting the recycling of organic matter into ecosystems. Most forensic
      studies are focused on succession of Diptera while neglecting Coleoptera. So far,
      little information is available on carrion beetles postmortem colonization and
      decomposition process in temperate biogeoclimatic countries. These beetles are
      however part of the entomofaunal colonization of a dead body. Forensic
      entomologists need databases concerning the distribution, ecology and phenology
      of necrophagous insects, including silphids. Forensic entomology uses pig
      carcasses to surrogate human decomposition and to investigate entomofaunal
      succession. However, few studies have been conducted in Europe on large
      carcasses. The work reported here monitored the presence of the carrion beetles
      (Coleoptera: Silphidae) on decaying pig carcasses in three selected biotopes
      (forest, crop field, urban site) at the beginning of spring. Seven species of
      Silphidae were recorded: Nicrophorus humator (Gleditsch), Nicrophorus vespillo
      (L.), Nicrophorus vespilloides (Herbst), Necrodes littoralis L., Oiceoptoma
      thoracica L., Thanatophilus sinuatus (Fabricius), Thanatophilus rugosus (L.). All
      of these species were caught in the forest biotope, and all but O. thoracica were
      caught in the agricultural biotope. No silphids were caught in the urban site.

PMID- 21867440
TI  - Effects of serine protease inhibitors on growth and development and digestive
      serine proteinases of the Sunn pest, Eurygaster integriceps.
AB  - In the current study the effects of serine proteinase inhibitors (TLCK, TPCK,
      SBTI, and a combination of SBTI and TPCK) with concentrations of 1% and 4% of
      dietary protein in artificial diets were tested against growth of the Sunn pest,
      Eurygaster integriceps Puton (Hemiptera: Scutelleridae), development, and its gut
      serine proteinase targets. Analysis of variance indicated that protease
      inhibitors affected nymphal development time, adult weight, and survival. Mean
      development time of third instar nymphs in control, SBTI (1%), TLCK (1%), and
      TPCK was 7.18, 9.74, 9.97, and 8.52 days, respectively. The highest mortality
      (100 % mortality) was observed when a combination of TPCK and SBTI, both at 4% of
      dietary protein, was used followed by TPCK (4%) that produced 95% mortality.
      There were significant differences in proteinase activity between treatments and
      controls when BApNA and SAAPFpNA were used as substrates for trypsin and
      chymotrypsin, respectively. Reduction of trypsin activity in insects fed with low
      doses of SBTI (1%), TLCK (1%), and both doses of TPCK (1% and 4%) was 40, 26, 23,
      and 17%, respectively. Inhibition of chymotrypsin activity was seen in the
      insects fed on SBTI (1%), TLCK (1%), and TPCK (4%) where inhibition was 14, 9,
      and 36%, respectively. Maximum inhibition of chymotrypsin activity was observed
      in the insects fed on diets containing high doses of TPCK (4%). In gel assays,
      the greatest effects were observed when E. integriceps were fed on high doses of
      SBTI and TPCK. Therefore, TPCK followed by SBTI proved to be the most effective
      proteinase inhibitors of E. integriceps.

PMID- 21867441
TI  - Hemocyte responses of the Colorado potato beetle, Leptinotarsa decemlineata, and
      the greater wax moth, Galleria mellonella, to the entomopathogenic nematodes,
      Steinernema feltiae and Heterorhabditis bacteriophora.
AB  - Hemocyte encapsulation reactions of infective juveniles of two Iranian isolates
      of the entomopathogenic nematodes, Heterorhabditis bacteriophora Poinar
      (Rhabditina: Heterorhabditidae) and Steinernema feltiae Filipjev (Tylenchina:
      Steinernematidae), were compared in the economic pest Colorado potato beetle,
      Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae), and the greater wax
      moth, Galleria mellonella L. (Lepidoptera: Pyralidae). The former was a more
      responsive host than the latter and the hemocyte responses occurred sooner and
      more extensively. Complete encapsulation of some of the nematodes occurred by 4 h
      post injection for H. bacteriophora in both L. decemlineata and G. mellonella,
      and by 2 h pi for S. feltiae in L. decemlineata. The percentage of encapsulation
      from 24 h to 72 h pi in L. decemlineata was 86.2% for S. feltiae and 39% for H.
      bacteriophora. In G. mellonella there were no encapsulation or melanization
      responses against S. feltiae, whereas when H. bacteriophora was encapsulated and
      melanized (16.7%) the encapsulation level was lower than in L. decemlineata. This
      study may contribute to effectively selecting entomopathogenic nematode species
      active against significant economic pests based on the latter's cellular immune
      response.

PMID- 21867442
TI  - The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light,
      and hair follicle apoptosis.
AB  - Infection rate, reaction to light, and hair follicle apoptosis are examined in
      the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the
      northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013)
      prevalence of D. canis infection. Infection during the investigation peaked each
      winter, with an average prevalence of 12.5% (32/255). The infection rates
      significantly varied in accordance with month, sex, age, and breed (p < 0.05).
      Most of the lesions were discovered on the backs of the infected animals, where
      the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of
      infection based on landscape area factor, found that employing a map-overlapping
      method showed a higher infection rate in the eastern distribution of Taiwan's
      northern area than other areas. Isolation tests for Microsporum canis Bodin
      (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard)
      on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2%
      (1/45), respectively. Observations demonstrated that D. canis slowly moved from a
      light area to a dark area. Skin samples were examined for cellular apoptosis by
      activated caspase3 immunohistochemical staining. Cells that surrounded the
      infected hair follicles were activated caspase3-positive, revealing cell
      apoptosis in infected follicles via the activation of caspase3.

PMID- 21867443
TI  - Detrimental and neutral effects of a wild grass-fungal endophyte symbiotum on
      insect preference and performance.
AB  - Seed-borne Epichloe/Neotyphodium Glenn, Bacon, Hanlin (Ascomycota: Hypocreales:
      Clavicipitaceae) fungal endophytes in temperate grasses can provide protection
      against insect attack with the degree of host resistance related to the grass
      endophyte symbiotum and the insect species involved in an interaction. Few
      experimental studies with wild grass-endophyte symbiota, compared to endophyte
      infected agricultural grasses, have tested for anti-insect benefits, let alone
      for resistance against more than one insect species. This study quantified the
      preference and performance of the bird cherry oat-aphid, Rhopalosiphum padi (L.)
      (Hemiptera: Aphididae) and the cereal leaf beetle, Oulema melanopus (L.)
      (Coleoptera: Chrysomelidae), two important pests of forage and cereal grasses, on
      Neotyphodium-infected (E+) and uninfected (E-) plants of the wild grass Alpine
      timothy, Phleum alpinum L. (Poales: Poaceae). The experiments tested for both
      constitutive and wound-induced resistance in E+ plants to characterize possible
      plasticity of defense responses by a wild E+ grass. The aphid, R. padi preferred
      E- over E+ test plants in choice experiments and E+ undamaged test plants
      constitutively expressed antibiosis resistance to this aphid by suppressing
      population growth. Prior damage of E+ test plants did not induce higher levels of
      resistance to R. padi. By contrast, the beetle, O. melanopus showed no preference
      for E+ or E- test plants and endophyte infection did not adversely affect the
      survival and development of larvae. These results extend the phenomenon of
      variable effects of E+ wild grasses on the preference and performance of
      phytophagous insects. The wild grass- Neotyphodium symbiotum in this study
      broadens the number of wild E+ grasses available for expanded explorations into
      the effects of endophyte metabolites on insect herbivory.

PMID- 21867444
TI  - Effects of associated bacteria on the pathogenicity and reproduction of the
      insect-parasitic nematode Rhabditis blumi (Nematoda: Rhabditida).
AB  - Three bacteria, Alcaligenes faecalis , Flavobacterium sp., and Providencia
      vermicola , were isolated from dauer juveniles of Rhabditis blumi . The
      pathogenic effects of the bacteria against 4th instar larvae of Galleria
      mellonella were investigated. Providencia vermicola and Flavobacterium sp. showed
      100% mortality at 48 h after haemocoelic injection, whereas A. faecalis showed
      less than 30% mortality. Dauer juveniles showed 100% mortality against G.
      mellonella larvae, whereas axenic juveniles, which do not harbor associated
      bacteria, exhibited little mortality. All of the associated bacteria were used as
      a food source for nematode growth, and nematode yield differed with bacterial
      species. Among the bacterial species, P. vermicola was most valued for nematode
      yield, showing the highest yield of 5.2 * 10(4) nematodes/mL in the plate. In
      bacterial cocultures using two of the three associated bacteria, one kind
      stimulated the other. The highest total bacterial yield of 12.6 g/L was obtained
      when the inoculum ratio of P. vermicola to A. faecalis was 10:1. In air-lift
      bioreactors, the nematode growth rate increased with an increasing level of
      dissolved oxygen. The maximum nematode yield of 1.75 * 10(5) nematodes/mL was
      obtained at 192 h with an aeration rate of 6 vvm.

PMID- 21867445
TI  - Effects of rosuvastatin on subclinical atherosclerosis and arterial stiffness in
      rheumatoid arthritis: a randomized controlled pilot trial.
AB  - OBJECTIVE: To ascertain the effect of rosuvastatin on carotid atherosclerosis and
      arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: Fifty RA
      patients were randomized in a double-blind placebo-controlled trial to receive 10
      mg rosuvastatin (n = 24) or placebo (n = 26). Patients were followed
      prospectively every 3 months for 12 months. Intima-media thickness (IMT),
      augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured
      at baseline, 6 and 12 months. RESULTS: Rosuvastatin resulted in statistically
      significant reductions of total cholesterol (TC), low density lipoprotein
      cholesterol (LDL-C), apolipoprotein B (Apo B), and urate levels vs. placebo.
      However, rosuvastatin had no significant effect on changes in inflammatory
      markers, including C-reactive protein (CRP) levels [from 2.9 (1.4-11.0) to 3.1
      (0.9-13.3) mg/L in the rosuvastatin group compared with from 5.8 (2.6-14.2) to
      4.4 (1.2-12.3) mg/L in the placebo group]. Nonetheless, a significant improvement
      in the Disease Activity Score (DAS) and a reduction in fibrinogen level was
      observed at 6 and 12 months compared with baseline in the rosuvastatin group. The
      treatment group exhibited a significant increase in SEVR (from 157 +/- 28% to 163
      +/- 33% in the rosuvastatin group compared with from 143 +/- 18% to 143 +/- 26%
      in the placebo group, p = 0.023), but no significant effect was observed in the
      changes in IMT and AIx. CONCLUSION: Our data suggest that rosuvastatin has a
      modest anti-inflammatory effect in RA patients with low disease activity in terms
      of reduction in DAS and fibrinogen level. Rosuvastastin may also improve
      subendocardial perfusion and lower the urate level.

PMID- 21867446
TI  - Genetics of muscle strength and power: polygenic profile similarity limits
      skeletal muscle performance.
AB  - Environmental and genetic factors influence muscle function, resulting in large
      variations in phenotype between individuals. Multiple genetic variants (polygenic
      in nature) are thought to influence exercise-related phenotypes, yet how the
      relevant polymorphisms combine to influence muscular strength in individuals and
      populations is unclear. In this analysis, 22 genetic polymorphisms were
      identified in the literature that have been associated with muscular strength and
      power phenotypes. Using typical genotype frequencies, the probability of any
      given individual possessing an "optimal" polygenic profile was calculated as
      0.0003% for the world population. Future identification of additional
      polymorphisms associated with muscular strength phenotypes would most likely
      reduce that probability even further. To examine the genetic potential for
      muscular strength within a human population, a "total genotype score" was
      generated for each individual within a hypothetical population of one million.
      The population expressed high similarity in polygenic profile with no individual
      differing by more than seven genotypes from a typical profile. Therefore,
      skeletal muscle strength potential within humans appears to be limited by
      polygenic profile similarity. Future research should aim to replicate more
      genotype-phenotype associations for muscular strength, because only five common
      genetic polymorphisms identified to date have positive replicated findings.

PMID- 21867447
TI  - What is the evidence for effectiveness of interventions to enhance coping among
      people living with HIV disease? A systematic review.
AB  - As new treatments enhance mortality, and infection rates continue to grow in many
      communities, the concept of "living well" with human immunodeficiency virus (HIV)
      infection is essential. The concept of coping has been well-articulated in the
      HIV literature and the public health argument for enhanced coping is crucial to
      reduce the burden of disease and health service use. This systematic review aimed
      to systematically identify and appraise the evidence for effectiveness in HIV
      coping interventions. A detailed search strategy was implemented and the retained
      papers entered into common tables for comparative analysis. Interventions were
      organised into models and data extracted on population, intervention description,
      tools and outcomes. Following review of all search returns against the
      included/excluded criteria of the search strategy, 28 peer review papers were
      retained. Models were psychological (n = 21), drug therapy (n = 3), spiritual (n
      = 1), diet and exercise (n = 1), mixed models (n = 1) and information management
      (n = 1). Sixteen of the 28 controlled studies found a significant intervention
      effect, and cognitive behaviour and stress management interventions offer
      particular effectiveness. Despite a lack of common outcome tolls, there are
      useful data that demonstrate effectiveness. Further studies must address outcomes
      for women and children.

PMID- 21867448
TI  - Canadian Punjabi Sikh men's experiences of lifestyle changes following myocardial
      infarction: cultural connections.
AB  - OBJECTIVE: To describe how culture underlies Canadian Punjabi Sikh men's
      experiences of adopting lifestyle changes following myocardial infarction (MI).
      DESIGN: Qualitative, interpretive design. In-depth, individual interviews were
      conducted with 27 Canadian Punjabi Sikh men post-MI. Data were analysed using
      constant comparative methods. RESULTS: Cultural influences were identified in
      Punjabi Sikh men's descriptions of their experience of adopting lifestyle
      changes. Actions related to self-care, rehabilitation and lifestyle change post
      MI were embedded in collectivist family and community contexts. Three themes,
      derived from the data, were found to intertwine with these contexts; they related
      to food consumption, physical exercise and faith and religion. CONCLUSION AND
      IMPLICATIONS: These findings highlight how collectivist ideals influence Canadian
      Punjabi Sikh men's adoption of lifestyle changes post-MI. The content and
      processes by which healthcare providers deliver heart health and rehabilitation
      to Canadian Punjabi Sikh men might be guided, at least in part, by the
      collectivist cultural practices underpinning our findings.

PMID- 21867449
TI  - Biomimetic extracellular matrix-incorporated scaffold induces osteogenic gene
      expression in human marrow stromal cells.
AB  - Engineering biomaterials mimicking the biofunctionality of the extracellular
      matrix (ECM) is important in instructing and eliciting cell response. The native
      ECM is highly dynamic and has been shown to support cellular attachment,
      migration, and differentiation. The advantage of synthesizing an ECM-based
      biomaterial is that it mimics the native cellular environment. However, the ECM
      has tissue-specific composition and patterned arrangement. In this study, we have
      employed biomimetic strategies to develop a novel collagen/chitosan template that
      is embedded with the native ECM of differentiating human marrow stromal cells
      (HMSCs) to facilitate osteoblast differentiation. The scaffold was characterized
      for substrate stiffness by magnetic resonance imaging and nanoindentation and by
      immunohistochemical analysis for the presence of key ECM proteins. Gene
      expression analysis showed that the ECM scaffold supported osteogenic
      differentiation of undifferentiated HMSCs as significant changes were observed in
      the expression levels of growth factors, transcription factors, proteases,
      receptors, and ECM proteins. Finally, we demonstrate that the scaffold had the
      ability to nucleate calcium phosphate polymorphs to form a mineralized matrix.
      The results from this study suggest that the three-dimensional native ECM
      scaffold directly controls cell behavior and supports the osteogenic
      differentiation of mesenchymal stem cells.

PMID- 21867450
TI  - Measurement of the pro-hormone of brain type natriuretic peptide (proBNP):
      methodological considerations and pathophysiological relevance.
AB  - Recent studies demonstrated that large amounts of the pro-hormone peptide of
      brain natriuretic peptide (proBNP) can be detected in plasma of healthy subjects
      and in particular of patients with heart failure. As a result, a great part of B
      type natriuretic peptides measured in patients with cardio-vascular disease may
      be devoid of biological activity. These findings stimulated the set up of
      specific immunoassay methods for the measurement of the intact proBNP peptide.
      The aim of this review article is to discuss the methodological characteristics
      and the possible clinical relevance of specific immunoassay methods for the
      measurement of the proBNP peptide. From an analytical point of view, a fully
      automated immunoassay of proBNP has some theoretical advantages (e.g., a more
      stable molecule with higher molecular weight than the derived peptides) compared
      to the active hormone BNP. Recent studies supported the concept that the
      precursor proBNP might be actually considered a circulating prohormone, which can
      be cleaved by specific plasma proteases in BNP, the active hormone, and NT
      proBNP, an inactive peptide. The peripheral processing of circulating proBNP
      could likely be submitted to regulatory rules, which might be impaired in
      patients with heart failure, opening new perspectives in the treatment of heart
      failure (e.g., by studying drugs inducing the cleavage of the prohormone into
      active BNP). Furthermore, as a future perspective, the specific assay in the same
      plasma sample of the intact precursor proBNP and of the biologically active
      peptide BNP, could allow a more accurate estimation of the production/secretion
      of B-type related peptides from cardiomyocytes and of the global cardiac
      endocrine function.

PMID- 21867451
TI  - A new system for the treatment of retinal degeneration.
AB  - Recent clinical studies indicate that stimulation of the retina with tiny amounts
      of current can have a therapeutic effect on retinal diseases such as retinitis
      pigmentosa. We have therefore developed a preventive treatment system which
      stimulates the eye with a thread electrode; among other objectives, the aim is
      that even blind patients can administer the therapy themselves under physician's
      supervision.

PMID- 21867452
TI  - Biopsychosocial predictors of preterm delivery.
AB  - AIM: The aim of this study is to integrate a psychosomatic approach in the
      investigation of causes for preterm deliveries. METHODS: A prospective study
      including 589 pregnant women between the 13(th) and the 24(th) gestation week
      (GW) was performed. In addition to medical and sociodemographic risk factors for
      preterm birth, factors such as biographical information, coping strategies and
      personality factors, pregnancy-related attitudes and anxieties as well as the
      pregnant women's social environment were examined. A factor analysis was
      performed using a principal component method with subsequent varimax rotation.
      RESULTS: Psychosocial variables were found to have a significant influence on the
      course of pregnancy and delivery. A total of 29 pregnant women (5.8%) delivered
      prematurely before they completed the 37(th) GW. Lack of support, poor emotional
      understanding by the partner, and additional stress subsequent to gynecological
      disorders were significantly associated with prematurity delivery. Pregnancy
      related fears and general anxiety were additional significant predictors for
      preterm delivery. CONCLUSIONS: Partner relationships, women's support groups,
      psychosomatic reactions due to problems with reproductive functions, and anxiety
      deserve special attention for the prevention of preterm birth.

PMID- 21867453
TI  - Decision-making at the border of viability by means of values clarification: a
      case study to achieve distinct communication by ordinary language approach.
AB  - OBJECTIVES: We set out to investigate the major obstacles in achieving a
      sensitive and supportive communication between parents and clinicians in ethical
      dilemma situations. We focused on discussions in emergency situations by means of
      values clarification. METHODS: The study population (n=141) covers four samples
      of clinical staff (n(1)=72) from different specialties and parents of preterm and
      term infants (n(2)=69). Because of the vulnerability of parents and the virulence
      of the topic, the descriptive qualitative case study comprises standardized
      questionnaires and half-standardized interviews. Data were analyzed graphically
      and statistically, comparing parents and professionals for the justification of
      acting using values clarification in this context. RESULTS: Our study indicated
      that the use of a critically reconsidered and less personalized language has to
      be a major goal in the care of preterm infants at the edge of viability.
      Furthermore we found that acting ethically means making decisions individually by
      using open-context terms sensitively in consideration of diverging action-guiding
      principles. CONCLUSIONS: Decisions in medicine concern different people - experts
      as well as patients and their representatives. The present study is an attempt to
      establish more awareness for improved communication, which is a part of
      professionalism, as well as coping strategies for all involved.

PMID- 21867454
TI  - Neonatal outcome using ultrathin fetoscope for laser coagulation in twin-to-twin
      transfusion syndrome.
AB  - OBJECTIVE: To improve neonatal outcome using ultrathin fetoscope for laser
      treatment of twin-to-twin transfusion syndrome. METHODS: Retrospective cohort
      study of a series of 80 cases of twin-to-twin-transfusion syndrome prior to 26
      weeks' gestation subjected to laser coagulation by means of a 1.0/1.2 mm fiber
      fetoscope with a sheath sectional area 2.65 mm(2)/3.34 mm(2) (n=27) and a 2.0 mm
      classic lens fetoscope with a sheath sectional area: 6.63 mm(2)/11.27 mm(2)
      (n=53). RESULTS: The survival rates of at least one twin in the compared groups
      were 94.4% (classic optic) and 100% (ultrathin optic), for both twins: 75.5% and
      83.3%, respectively. By decreasing sheath diameter a pregnancy was prolonged by
      an average of 21.3 days (P=0.0045), with a resulting increase in the recipient's
      weight of 389 g (P=0.0049) and an increase in the donor's Apgar score. However,
      the intervention with ultrathin optic took 11 min longer (P=0.031). CONCLUSION:
      The reduction of the iatrogenic damage of the amniotic membrane using ultrathin
      fetoscope with a small sheath, significantly improves the neonatal outcome after
      laser treatment of twin-to-twin-transfusion syndrome. The operator should only
      commence working with the 1 mm fetoscope after the learning curve has been
      accomplished.

PMID- 21867455
TI  - Energy metabolism in umbilical endothelial cells from preterm and term neonates.
AB  - AIM: The aim of this study was to investigate the impact of gestational age on
      energy metabolism in human umbilical vein endothelial cells (HUVECs) of preterm
      and term neonates. METHODS: Activities of respiratory chain (RC) complexes I-V,
      citrate synthase (CS), overall mitochondrial fatty acid oxidation (FAO),
      carnitine palmitoyltransferase 2 (CPT2), glycolytic enzymes as well as energy
      rich phosphates in HUVECs from uncomplicated term and preterm pregnancies were
      measured. Neonatal acylcarnitine profiles were analyzed postpartum. RESULTS:
      Activities of RC complexes II+III, IV, V, and CS were higher in HUVECs from
      immature pregnancies. Overall FAO did not change, whereas CPT2 activity was
      higher in term neonates. RC complexes II-V and CS correlated inversely to
      gestational age, as well as CPT2 activity within the term cohort.
      Phosphofructokinase activity increased with maturation; lactate dehydrogenase and
      hexokinase as well as energy-rich phosphates remained constant. In blood, long
      chain acylcarnitines were higher in term neonates. CONCLUSIONS: Gestational age
      dependent differences of energy-providing pathways in HUVECs were shown.
      Alterations of RC complexes with gestational age may be an adaptive process to
      cope with metabolic stress during birth; reduced oxidative phosphorylation and
      high glycolytic activity make HUVECs less susceptible to peripartum hypoxic
      damage. We hypothesize that HUVECs of premature neonates are metabolically
      maladapted to birth, which may be responsible for perinatal complications.

PMID- 21867456
TI  - Hepatoprotective constituents of Torilis radiata Moench (Apiaceae).
AB  - An investigation of the aqueous ethanolic extract (AE) of the aerial parts of
      Torilis radiata Moench yielded two triterpenes (lupeol acetate (1) and alpha
      amyrin (2)), a sterol (spinasterol (3)) from its n-hexane fraction (HF), a
      flavone (acacetin (4)), a coumarin (scopoletin (5)), a phenolic acid (ferulic
      acid (6)) from the chloroform fraction (CF) and a flavone glycoside (luteolin-7-O
      glucoside (7)) from the n-butanol fraction (BF). The hepatoprotection of the AE
      and its fractions was assessed in terms of the reduction in histological damage,
      accompanied by restoration of the liver enzymes (alanine amino transferase (ALT),
      aspartate amino transferase (AST), lactate dehydrogenase (LDH)), a reduction in
      the inflammatory markers (tumour necrosis-alpha (TNF-alpha), nitric oxide (NO), N
      acetyl-beta-D-glucosaminidase (NAG) and myloperoxidase (MPO) in serum) and
      restoration of the oxidant balance by decreasing the serum and hepatic
      malondialdehyde (MDA) levels, along with increasing the activity of hepatic
      catalase (CAT), glutathione peroxidase (GSHPx) and the non-enzymatic antioxidant
      glutathione (GSH).

PMID- 21867457
TI  - Synthesis of (-)-arctigenin derivatives and their anticancer activity.
AB  - The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin, which was
      prepared from fructus arctii, showed obvious anticancer activity. The synthesis
      of four new (-)-arctigenin derivatives and their anticancer bioactivities were
      examined. The structures of the four new synthetic derivatives were elucidated.

PMID- 21867458
TI  - Chemical and biological study of the seeds of Eragrostis tef (Zucc.) Trotter.
AB  - A chemical study of the red type of the seeds of Eragrostis tef (Zucc.) Trotter
      (Poaceae) led to the isolation of seven compounds from its ethanol extract,
      namely beta-sitosterol (1), beta-amyrin-3-O-(2'-acetyl(glucoside (2), beta
      sitosterol-3-O-beta-D-glucoside (3), naringenin (4), naringenin-4'-methoxy-7-O
      alpha-L-rhamnoside (5), eriodictyol-3',7-dimethoxy-4'-O-beta-D-glucoside (6) and
      isorhamnetin-3-O-rhamnoglucoside (7), which are reported for the first time in
      the genus Eragrostis. This is the first report for the isolation of compounds (2)
      and (6) in nature. The isolated compounds were identified using different
      spectroscopic methods (EIMS, UV, 1H NMR, 13C NMR, HMQC and HMBC). A proximate
      analysis revealed the high nutritive value of the seeds: carbohydrates (57.27%),
      protein (20.9%), essential amino acids (8.15%) with major leucine and lysine
      (1.71 and 1.35%, respectively), vitamin B1 (1.56 mg/100 g) and potassium and
      calcium (32.4 and 9.63%, respectively). The seeds yielded 22% w/w of fixed oil
      rich in unsaturated fatty acids (72.46%), among which oleic acid, was predominant
      (32.41%), followed by linolenic acid (23.83%). The ethanolic extract and fixed
      oil of the seeds exhibited anti-hyperlipedaemic and anti-hyperglycaemic
      activities. Oral administration of the fixed oil for 10 days resulted in a rise
      in serum calcium levels in rats.

PMID- 21867459
TI  - Management of patients with type 2 diabetes.
AB  - BACKGROUND: The number of treatment options in the diabetes arena has grown
      dramatically in a short period of time, with a corresponding increase in the
      breadth and depth of literature from which physicians and diabetes organizations
      make evidence-based decisions. Thus, the purpose of this article is to provide an
      up-to-date review of the literature describing current treatment options and
      guidelines available for the management of type 2 diabetes and prevention of its
      complications. METHODS: Pubmed searches were conducted for recent literature
      pertaining to the prevention of complications in type 2 diabetes. Comprehensive
      search terms were devised to identify articles describing micro- and
      macrovascular complications including nephropathy, neuropathy, retinopathy, and
      cardiovascular disease associated with type 2 diabetes. CONCLUSIONS: The current
      body of literature demonstrates that a significant reduction in the incidence of
      diabetic complications is achievable with early initiation and long-term
      maintenance of controlled blood glucose and cardiovascular risk factors.
      Screening for diabetic complications should be initiated early and continued at
      regular intervals to ensure early pharmacological intervention.

PMID- 21867460
TI  - Unexpectedly high frequency of European parentage in Venezuelan patients with
      chronic lymphocytic leukemia.
AB  - There is insufficient information on the characteristics of chronic lymphocytic
      leukemia (CLL) in Latin American patients. Immunoglobulin variable-region heavy
      chain (IGVH) gene usage and mutation status and prognostic factors were
      investigated in patients resident in Venezuela. The most frequently used IGVH
      family genes were: VH3 > VH1 > VH4 > VH5, with a high incidence of IGVH1.69 and
      IGVH3.21 genes, and 55.2% of IGVH genes were mutated. Analysis of HCDR3 (third
      complementarity-determining region of the heavy chain) revealed that 24% of
      Venezuelan HCDR3s belonged to a CLL stereotyped HCDR3. Results for prognostic
      factors were similar to those reported previously for Caucasian populations.
      Interestingly, we found an over-representation of people of European extraction
      among Venezuelan patients with CLL, suggesting the possibility of a higher
      frequency of susceptibility genes for CLL in Europeans in comparison with Latin
      American mestizos.

PMID- 21867461
TI  - 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography
      in symmetrically enlarged axillary and inguinal lymph nodes of Ofuji's
      papuloerythroderma.

PMID- 21867462
TI  - A gamma-delta T cell lymphoma with a mask face.

PMID- 21867463
TI  - Cyclodextrin-based siRNA delivery nanocarriers: a state-of-the-art review.
AB  - INTRODUCTION: The discovery of synthetic small interfering RNA (siRNA) has led to
      a surge of interest in harnessing RNA interference (RNAi) technology for
      biomedical applications and drug development. Even though siRNA can be a powerful
      therapeutic drug, its delivery remains a major challenge, due to the difficulty
      in its cellular uptake. Naked siRNA has a biological half-life of less than an
      hour in human plasma. To increase the lifetime and improve its therapeutic
      efficacy, non-viral vectors have been developed. As a natural evolution,
      cyclodextrins (CDs), which are natural cyclic oligosaccharides, have recently
      been applied as delivery vehicles for siRNA, and this in turn, has led to a surge
      of interest in this area. AREAS COVERED: This review discusses the recent
      advances made in the design of delivery strategies for siRNA, focusing on CD
      based delivery vectors, because these have demonstrated clinical success. The
      methods of preparation of CD-based vectors, their characterization, transfection
      efficiencies, cellular toxicity, preclinical and clinical trials are also
      addressed, as well as future therapeutic applications. EXPERT OPINION: siRNA
      mediated RNAi therapeutics is beginning to transform healthcare, particularly,
      for the treatment of solid tumors. For example, CALAA01, a targeted, self
      assembling nanoparticle system based on CD complexed with siRNA has been
      effective in phase I clinical trials. Although siRNA therapeutics suffers from
      problems related to off-target effects and non-specific gene silencing, these
      problems can be overcome by reducing the nanoparticle size, improving the
      targeting efficiency and by modifying the primary sequence of the siRNA.

PMID- 21867464
TI  - Variability in chemokine-induced adhesion of human mesenchymal stromal cells.
AB  - BACKGROUND AIMS. Intravenously applied mesenchymal stromal cells (MSC) are under
      investigation for numerous clinical indications. However, their capacity to
      activate shear stress-dependent adhesion to endothelial ligands is incompletely
      characterized. METHODS. Parallel-plate flow chambers were used to induce firm
      adhesion of MSC to integrin ligand vascular cell adhesion molecule (VCAM)-1.
      Human MSC were stimulated by chemokine (C-C motif) ligand (CCL15)/macrophage
      inflammatory protein (MIP-5), CCL19/MIP-3beta chemokine (C-X-C motif) ligand
      (CXCL8)/interleukin (IL)-8, CXCL12/ stromal derived factor (SDF-1) or CXCL13/B
      lymphocyte chemoattractant (BLC). RESULTS. Two MSC isolates responded to three
      chemokines (either to CCL15, CCL19 and CXCL13, or to CCL19, CXCL12 and CXCL13),
      two isolates responded to two chemokines (to CCL15 and CCL19, or to CCL19 and
      CXCL13), and one isolate responded to CCL19 only. In contrast, all tested MSC
      isolates responded to selectins (P-selectin and E-selectin) or integrin ligand
      VCAM-1, as visualized by a velocity reduction under flow. CONCLUSIONS. Inter
      individual variability of chemokine-induced integrin activation should be
      considered when evaluating human MSC as cellular therapies.

PMID- 21867465
TI  - Cell recovery comparison between plasma depletion/reduction- and red cell
      reduction-processing of umbilical cord blood.
AB  - BACKGROUND AIMS: Limited cell dose has hampered the use of cord blood
      transplantation (CBT) in adults. One method of minimizing nucleated cell loss in
      cord blood (CB) processing is to deplete or reduce plasma but not red blood cells
      - plasma depletion/reduction (PDR). METHODS: The nucleated cell loss of PDR was
      studied, and determined to be less than 0.1% in the discarded supernatant plasma
      fraction in validation experiments. After testing and archival sampling, the
      median nucleated cell recovery for PDR processing was 90%, and median CD34(+)
      cell recovery 88%. In a CB bank inventory of 12 339 products with both pre- and
      post-processing total nucleated cells (TNC), PDR processing resulted in median
      post-processing TNC recoveries of 90.0% after testing and archival samples
      removal. Using the same 10 CB units divided into two halves, we compared directly
      the recovery of PDR against hydroxyethyl starch red cell reduction (RCR) for TNC,
      CD34(+) cells and colony-forming units (CFU-GM, CFU-E, CFU-GEMM and total CFU)
      after parallel processing. We also compared the loss of very small embryonic-like
      stem cells (VSEL). RESULTS: We demonstrated significantly higher recoveries using
      PDR for TNC (124%), CD34(+) cells (121%), CFU-GM (225%), CFU-GEMM (201%), total
      CFU (186%) and VSEL (187%). The proportion of high TNC products was compared
      between 10 912 PDR and 38 819 RCR CB products and found to be 200% higher for
      products that had TNC >=150 * 10(7) (P = 0.0001) for the PDR inventory.
      CONCLUSIONS: Our data indicate that PDR processing of CB provides a significantly
      more efficient usage of this valuable and scarce resource.

PMID- 21867466
TI  - A cross-sectional study of umbilical cord blood donor profiles and their
      influence on umbilical cord blood collection in a Brazilian hospital.
AB  - BACKGROUND AIMS: Umbilical cord blood (UCB) cells are a new alternative to bone
      marrow source for hematopoietic stem cell transplantation and their use has
      increased in the last decade. Thus efforts are being made to improve the
      umbilical cord blood unit's quality. Besides compatibility, other factors, such
      as the total nucleated cell (TNC) count and the percentage of CD34(+) cells in
      the product, are very important for a successful transplant outcome. Our aim was
      to describe our donor population and assess the best cord blood collection
      technique at Hospital Israelita Albert Einstein's cord blood bank (Sao Paulo,
      Brazil). METHODS: This was a retrospective study in which all analyses were
      performed simultaneously. A Student's t-test was used for qualitative variables
      for non-matched samples. For qualitative analyses, we used either the chi-square
      test or the exact Fisher's test. RESULTS: The stratification of the population
      characteristics allowed us to determine which ones had an impact on unit volume,
      TNC count and percentage of CD34(+) cells. A significant correlation was observed
      between donor characteristics and the quality of UCB units as related to maternal
      and gestational age, type of pregnancy, route of delivery, cord blood collection
      technique and birth weight. CONCLUSIONS: We found that cord blood collection
      technique and newborn weight were significantly correlated with the TNC content.
      The collection technique used at our institution significantly improved the UCB
      unit volume and consequently the TNC count. Some findings, such as the impact of
      maternal age and newborn weight, have led us to re-evaluate our protocol in order
      to achieve better results.

PMID- 21867467
TI  - Short-term gentamicin therapy and risk of renal toxicity in patients with
      bacteraemia.
AB  - The renal safety of gentamicin has been questioned even when dosed once daily.
      This retrospective cohort study comprised adult patients with community-acquired
      bacteraemia and no record of chronic renal disease or malignancy. We included
      patients treated with gentamicin once daily for <= 5 days (165 exposed patients)
      and a balanced sample of patients not receiving aminoglycosides (150 non-exposed
      patients). The primary endpoint, which was an elevation in plasma creatinine of >
      40 MUmol/l from baseline, was equally common among exposed (7.9%) and non-exposed
      patients (8.7%) (p = 0.80). Among 26 patients with the primary endpoint, follow
      up creatinine levels were evaluable in 21 patients and reached the normal range
      in 8/12 (67%) exposed patients and in 7/9 (78%) non-exposed patients (p = 0.66).
      Thirty-day mortality was 7.9% in exposed patients versus 7.3% in non-exposed
      patients (p = 0.86). We conclude that renal impairment in bacteraemic patients is
      independent of short-term (<= 5 days) gentamicin administration.

PMID- 21867468
TI  - Detection of microbial diversity in endocarditis using cultivation-independent
      molecular techniques.
AB  - BACKGROUND: The aim of this study was to investigate whether the diagnosis of
      infective endocarditis (IE) could be improved using molecular tools in addition
      to standard microscopy and cultivation methods. METHODS: Cultivation was
      performed on blood or tissue samples as recommended in the modified Duke
      criteria. The molecular tools included a broad-range polymerase chain reaction
      (PCR)-based denaturant gradient gel electrophoresis and a more detailed
      identification by constructing clone libraries followed by sequencing. RESULTS:
      Of 14 patients, 12 were positive by blood or tissue cultivation and all were
      monomicrobial. Molecular methods showed the presence of DNA from multiple
      bacterial species in 6 of the samples and indicated a larger variety of bacteria
      in the different samples than identified by cultivation. For 8 of the patients
      there was a good correlation between the results of cultivation and molecular
      methods, and for these samples the identified bacteria are known to be frequently
      involved with IE. Many of the additional bacteria only identified by the
      molecular methods are not reported as common causes of IE. CONCLUSIONS:
      Application of molecular tools in addition to cultivation indicated that
      polymicrobial infections might be of importance in IE. However, the significance
      of the more unknown microorganisms needs to be investigated further.

PMID- 21867469
TI  - Skin and soft tissue infections: experience over a five-year period and clinical
      usefulness of ultrasonography-guided gun biopsy-based culture.
AB  - BACKGROUND: Skin and soft tissue infections (SSTIs) are common clinical diseases,
      but only a few reports of microbiological data on SSTIs in Korea have been
      published. In practice, specimens are rarely obtained from infected lesions
      unless there is visible pus or an abscess pocket. However, identification of the
      causative pathogen is important, because of emerging drug resistance and the
      increase in immunocompromised hosts. METHODS: The medical records of 760 adult
      cases of community-acquired SSTIs (CA-SSTIs) from September 2003 to August 2008
      were reviewed retrospectively. We analyzed epidemio-clinical features and
      microbiological distributions of CA-SSTIs and evaluated the positive culture rate
      of several diagnostic methods, including swab, tissue biopsy, blind needle
      aspiration, ultrasonography (US)-guided needle aspiration, and US-guided gun
      biopsy. RESULTS: Most CA-SSTIs (76.1%) occurred in previously healthy persons
      without underlying diseases. Re-infections were identified in 76 (10%) patients
      and cirrhosis was an independent risk factor for re-infection (odds ratio 3.64,
      95% confidence interval 1.36-9.76). The most commonly identified pathogen was
      methicillin-susceptible Staphylococcus aureus, and 3(rd)-generation
      cephalosporins were the most commonly used empirical antibiotics (47.9%). US
      guided needle aspiration had a high positive culture rate of 73.9% and the
      positive culture rate of US-guided gun biopsy was 17.5%. CONCLUSIONS: Considering
      the microbiological distribution of CA-SSTIs in Korea, penicillinase-stable
      penicillin or a 1(st)-generation cephalosporin should be adequate for initial
      antibiotic treatment. US-guided needle aspiration was a good technique for the
      identification of causative pathogens, and additive productivity is expected with
      US-guided gun biopsy culture from lesions without fluid collection.

PMID- 21867470
TI  - Seasonal variations of 15 respiratory agents illustrated by the application of a
      multiplex polymerase chain reaction assay.
AB  - BACKGROUND: Nucleic acid amplification tests are increasingly being used to
      diagnose viral and bacterial respiratory tract infections. The high sensitivity
      of these tests affects our understanding of the epidemiology of respiratory tract
      infections. We have assessed the detection rate of a multiplex real-time
      polymerase chain reaction (PCR) test, with emphasis on epidemiology and seasonal
      distribution of the most common respiratory tract infections. METHODS: Seven
      thousand eight hundred and fifty-three nasopharyngeal samples from 7220 patients
      (age range 0-98 y, median 22 y) obtained during 36 consecutive months (November
      2006-October 2009), were analyzed with a multiplex PCR panel including influenza
      A (IfA) and B (IfB) virus, parainfluenza virus (PIV) 1-3, respiratory syncytial
      virus (RSV), human rhinovirus (HRV), human coronavirus (CoV) OC43, NL63, and
      229E, human metapneumovirus (HMPV), adenovirus (AdV), enterovirus (EV), and 2
      bacteria--Mycoplasma pneumoniae and Chlamydophila pneumoniae. RESULTS: Of the
      total samples, 44.5% (n = 3496) were positive for at least 1 agent, with HRV
      being the most common (n = 1482, 38.0%), followed by RSV (n = 526, 13.5%) and IfA
      (n = 403, 10.3%). The diagnostic yield was significantly higher during the winter
      and early spring compared to the summer (n = 2439 of 4458 samples, 54.7% and n =
      1057 of 3395 samples, 31.1%, respectively; p < 0.001). CONCLUSIONS: The
      diagnostic yield was highly dependent on the month of sampling and the age of the
      patient. However, the overall detection rate per month was above 30%, apart for
      August and September. Our findings support the use of similar tests in routine
      clinical care all year round. HRV was the most common finding in the respiratory
      tract, independent of season.

PMID- 21867471
TI  - Can risk factors for infectious illnesses in children at day care centres be
      identified?
AB  - BACKGROUND: The risk factors for febrile, respiratory, and gastrointestinal
      illnesses in preschool children at day care centres have not been adequately
      identified and may differ between countries. METHODS: In this repeated cross
      sectional and longitudinal study of children at day care centres, we analyzed
      various potential risk factors for infectious illnesses using a mixed effect
      hierarchical Poisson regression model. The results of the analyses and the
      incidence rates of these illnesses are reported herein. RESULTS: The study lasted
      2.5 y (2000-2003) and was divided into five 6-month periods (seasons). Nine
      hundred and seventeen children participated, and their mean age within each
      season was 3.6-4.1 y. The only consistent risk factors identified were young age
      and winter season. No consistent risk factors at the day care centres (facilities
      or hygiene practices) were identified. The incidences of the febrile,
      respiratory, and gastrointestinal illnesses varied significantly between seasons
      (winter/summer) and between age groups. CONCLUSIONS: Risk factors of infectious
      illnesses are difficult to identify and because they may vary between countries,
      international recommendations on expensive intervention strategies are not
      justifiable. Rates of respiratory illnesses in Icelandic preschool children
      appear higher than in other countries, but rates of gastrointestinal illnesses
      lower.

PMID- 21867472
TI  - Colonization with Staphylococcus aureus in Swedish nursing homes: a cross
      sectional study.
AB  - BACKGROUND: Screening for bacterial colonization among risk populations could
      provide better estimates of the volume of the bacteria-related disease reservoir
      and the level of antimicrobial resistance, than do conventional laboratory
      reports. METHODS: Two hundred and one participants at 10 Swedish nursing homes
      were screened for colonization with Staphylococcus aureus between January and
      October 2009. Of the 201 participants, 61 (30%) were male. The median age was 86
      y. All participants were systematically sampled from the nasal mucosa, the
      pharyngeal mucosa, the groin, and active skin lesions, if any. RESULTS: Ninety
      nine of 199 participants (50%) were colonized with S. aureus. The colonization
      rate was 34% for the nose, 35% for throat, 10% for groin, and 54% for active skin
      lesions. An antibiotic-resistant S. aureus isolate was identified in 8.5% of all
      participants regardless of colonization status. A total of 24 resistant isolates
      were detected, and 21 of these were resistant to fluoroquinolones. There was no
      case of colonization with methicillin-resistant S. aureus (MRSA). CONCLUSIONS:
      The presence of resistant isolates was generally low, and the greater part of the
      resistance was fluoroquinolone-related. To achieve reasonable precision,
      screening programmes of this kind must include samples from both the nose and
      throat, and, although low, the prevalence of antimicrobial resistance in Swedish
      nursing homes still calls for reflection on how to use the fluoroquinolones
      wisely.

PMID- 21867473
TI  - Diphtheria outbreak in Norway: lessons learned.
AB  - We describe an outbreak of diphtheria in Norway that occurred in 2008 and
      affected 3 unvaccinated family members. The epidemic caught the public health
      system off-guard on most levels; the diagnosis was distrusted due to its rarity,
      no diphtheria anti-toxin was available, and notification procedures were not
      rigorously followed.

PMID- 21867474
TI  - Pyogenic liver abscess caused by Pseudomonas aeruginosa: clinical analysis of 20
      cases.
AB  - BACKGROUND: There are few reports of Pseudomonas aeruginosa liver abscess (PALA)
      in the literature, and clinical information regarding its risk factors, route of
      transmission, and clinical course remains limited. METHODS: The medical records
      of 1076 patients with pyogenic liver abscess treated at Chang Gung Memorial
      Hospital were reviewed. RESULTS: Twenty of the patients whose records were
      analyzed had PALA. Mortality was 20%. Five patients with PALA, diagnosed
      immediately following an intra-abdominal surgical or endoscopic procedure, were
      classified as group A. The latent phase for the development of PALA in this group
      was less than 3 weeks. The remaining 15 patients were further subgrouped into
      group B (n = 8), with a traceable intra-abdominal procedure, and group C (n = 7),
      with no history of an invasive intra-abdominal procedure. The latent period in
      patients in group B varied from 6 weeks to 3.7 y. The absence of multidrug
      resistance in P. aeruginosa isolates from group C suggests the community-acquired
      nature of the infection in this group. Risk factor analysis showed that the
      incidence of hepatobiliary co-morbidities was high in all the groups (100%, 88%,
      and 71% in groups A, B, and C, respectively). The rates of co-infection with
      human gastrointestinal tract flora were 20%, 50%, and 71% in groups A, B, and C,
      respectively. CONCLUSIONS: PALA may be found in subjects without conventional
      risk factors for P. aeruginosa infection. In addition to patients with a
      preceding contaminated procedure, those with hepatobiliary co-morbidities form
      another high-risk group for this condition.

PMID- 21867475
TI  - Infectious disease specialist telephone consultations requested by general
      practitioners.
AB  - BACKGROUND: Infectious diseases (ID) make up a substantial part of a general
      practitioner's (GP's) workload. GPs frequently solicit ID specialists requesting
      advice on managing their patients with ID. The objectives of this study were to
      examine GP reasons for soliciting ID consultations and to assess the GPs' and
      specialists' opinions of the ID consultation service. METHODS: This was a
      prospective study of consecutive solicited ID consultations requested by GPs from
      the ID specialists of a 2200-bed university-affiliated hospital, conducted
      between October 2008 and March 2009. Data related to GP characteristics, their
      reasons for requesting the consultation, the recommendations given by the
      specialists, and the specialists' perceptions of the exchange were collected. GPs
      were asked to report their adherence to recommendations and their perceptions of
      the consultations. RESULTS: A mean of 57 telephone consultations per month were
      requested by GPs during the study period. ID specialist recommendations were
      related to antibiotic treatment (66.2%), diagnostic or monitoring tests (46.5%),
      and a subsequent formal consultation or hospitalization (29.6%). The reasons
      reported for GPs requesting an ID consultation were related to patient management
      (96.5%), rapidity of access (86.3%), and quality of care improvement (84.2%). GPs
      were satisfied with the telephone consultations in 97.9% of cases and ID
      specialists in 94.7%. CONCLUSIONS: Telephone consultations with ID specialists
      were widely appreciated by GPs, probably due to the accessibility of these
      specialists. Further study is needed to assess the effects of these telephone
      consultations on quality of care.

PMID- 21867476
TI  - The safety and tolerability evaluation of DepoFoam bupivacaine (bupivacaine
      extended-release liposome injection) administered by incision wound infiltration
      in rabbits and dogs.
AB  - OBJECTIVE: DepoFoam bupivacaine (DB) is in development for prolonged
      postoperative analgesia. Studies were conducted to evaluate the potential local
      and systemic toxicity and any effect on wound healing after wound infiltration.
      METHODS: The model simulates an inguinal hernia (skin incision ~2.5 and 5.5 cm).
      Animals (four/sex/group of each species) received DB 9, 18 or either 25 or 30
      mg/kg, bupivacaine solution (B(sol); 7.5 mg/ml, 9 mg/kg) or saline. DB was given
      at 0.6, 1.2 and 1.0 or 1.2 ml/kg, respectively, and B(sol) or saline at 1.2
      ml/kg. Each dose was infiltrated in small fractions on Day 1. End points included
      histology on Days 3 and 15. Wound healing was recorded on Day 2 through Day 15.
      RESULTS: There was no adverse effect in either species. Notably, granulomatous
      inflammation was noted in surgical sites from 8 of 24 rabbits in the DB groups
      only. Based on the minimal to mild severity on Day 15, this was considered a
      normal reaction against the liposomes. Except for granulomatous inflammation,
      there were no differences in overall incidence or severity of histologic changes
      in the sites dosed to DB, saline or B(sol). CONCLUSIONS: The data reported here
      are the first demonstration of the safety of DB in toxicology species.

PMID- 21867477
TI  - Recent patents involving virus nucleotide sequences; host defense, RNA silencing
      and expression vector strategies.
AB  - Improved knowledge of the molecular biology of viruses, including recent gains in
      virus sequence data analysis, has greatly contributed to recent innovations in
      medical diagnostics, therapeutics, drug development and other related areas.
      Virus sequences have been used for the development of vaccines and antiviral
      agents to block the spread of viral infections, as well as to target and battle
      chronic diseases such as cancer. Virus sequences are now routinely employed in a
      wide array of RNA silencing technologies. Viruses can also be engineered into
      expression vectors which in turn can be used as protein production platforms as
      well as delivery vehicles for gene therapies. This review article outlines a
      number of patents that have been recently issued with respect to virus sequence
      data and describes some of their biotechnological applications.

PMID- 21867478
TI  - Gene patents related to common diseases of the eye.
AB  - Visual impairment and blindness impose substantial morbidity and premature
      mortality on the population. The direct costs for vision disorders have been
      shown to be more than the cost of coronary heart disease, stroke, arthritis or
      depression and were estimated to be $9.85 billion in 2004 in Australia. Hence it
      is important to identify the causes of common eye diseases and understand their
      aetiology which in turn would allow determination of better management strategies
      and treatment options. Age related Macular Degeneration, Cataract, Diabetic
      Retinopathy, Glaucoma and uncorrected refractive errors represent the majority of
      the visual impairment and blindness in Australia and various parts of the world.
      This article reviews the gene patents available for these eye conditions and
      highlights the important discoveries that have so far contributed to our
      understanding of these diseases and provides valuable information as to where
      research will be heading in the future.

PMID- 21867479
TI  - Bacterial L-arabinose isomerases: industrial application for D-tagatose
      production.
AB  - D-tagatose is a natural monosaccharide with a low caloric value and has an anti
      hyperglycemiant effect. This hexose has potential applications both in
      pharmaceutical and agro-food industries. However, the use of D-tagatose remains
      limited by its production cost. Many production procedures including chemical and
      biological processes were developed and patented. The most profitable production
      way is based on the use of L-arabinose isomerase which allows the manufacture of
      D-tagatose with an attractive rate. Future developments are focused on the
      generation of L-arabinose isomerases having biochemical properties satisfying the
      industrial applications. This report provides a brief review of the most recent
      patents that have been published relating to this area.

PMID- 21867480
TI  - The role of estrogen and estrogen receptors in chemoresistance.
AB  - Drug resistance is one of the major obstacles limiting the success of cancer
      chemotherapy. Biological mechanisms contributing to drug resistance may be
      present de novo and related to inherent features or may be raised after exposure
      to anticancer drugs. In recent years, both clinical observations and experimental
      studies suggested that steroid hormones and their receptors might also affect the
      therapeutic efficacy of antineoplastic drugs. Estrogens and estrogen receptors
      (ER) are well-known for their critical roles in the development and progression
      of breast tumors. It has long been known that breast tumors expressing ERalpha
      protein (ERalpha+) behave in a fundamentally different fashion than ERalpha
      negative (ERalpha-) tumors with regard to their responses to hormonal therapy.
      Data obtained from both laboratory and clinical investigations suggested that
      some chemotherapeutic agents are clearly less effective in ERalpha+ tumors than
      ERalpha- tumors, although the mechanisms of ERalpha-mediated chemoresistance are
      not entirely clear. Moreover, recent studies from our laboratory and others
      demonstrated that the combination of antiestrogenic agents with chemotherapeutic
      drugs is of significant therapeutic benefit in ERalpha+ breast cancer over
      chemotherapy alone. In addition, the ERalpha-derived peptides, microRNAs
      specifically targeting ERalpha, as well as agents targeting estrogen-related
      receptors (ERRs) may hold promise to sensitize ERalpha+ breast tumors to
      chemotherapy. Considering that ERs are expressed in ~ 65% of human breast cancer,
      the ERalpha-mediated chemoresistance has become a big challenge for clinical
      treatment. The hope to overcome this drug resistance relies on further
      clarification of specific pathways or molecules contributing to the resistance.
      More exhaustive and systematic studies are essential to reach deeper
      understandings on the underlying mechanisms and to develop novel approaches to
      sensitize ERalpha+ breast tumors to chemotherapy.

PMID- 21867481
TI  - High-throughput, 384-well, LC-MS/MS CYP inhibition assay using automation,
      cassette-analysis technique, and streamlined data analysis.
AB  - Here we describe a high capacity and high-throughput, automated, 384-well CYP
      inhibition assay using well-known HLM-based MS probes. We provide consistently
      robust IC(50) values at the lead optimization stage of the drug discovery
      process. Our method uses the Agilent Technologies/Velocity11 BioCel 1200 system,
      timesaving techniques for sample analysis, and streamlined data processing steps.
      For each experiment, we generate IC(50) values for up to 344 compounds and
      positive controls for five major CYP isoforms (probe substrate): CYP1A2
      (phenacetin), CYP2C9 ((S)-warfarin), CYP2C19 ((S)-mephenytoin), CYP2D6
      (dextromethorphan), and CYP3A4/5 (testosterone and midazolam). Each compound is
      incubated separately at four concentrations with each CYP probe substrate under
      the optimized incubation condition. Each incubation is quenched with acetonitrile
      containing the deuterated internal standard of the respective metabolite for each
      probe substrate. To minimize the number of samples to be analyzed by LC-MS/MS and
      reduce the amount of valuable MS runtime, we utilize timesaving techniques of
      cassette analysis (pooling the incubation samples at the end of each CYP probe
      incubation into one) and column switching (reducing the amount of MS runtime).
      Here we also report on the comparison of IC(50) results for five major CYP
      isoforms using our method compared to values reported in the literature.

PMID- 21867482
TI  - Effects of ranolazine on cardiovascular system.
AB  - Chronic stable angina affects 6-7 million Americans and contributes to a
      significant reduction in quality of life and life expectancy. Current
      pharmacotherapy for reducing episodes of exertional angina includes beta
      blockers, calcium channel blockers and long-acting nitrates. Patients may have
      contraindications to the use of one or more of these agents or be unable to
      tolerate initial or larger therapeutic doses. As a result of the inability of
      current management strategies to optimally control episodes of chronic angina,
      new therapies have been investigated that do not have some of the limitations of
      current therapies. New therapies for chronic stable angina are based on a
      mechanism involving membrane current such as the funny current and the late Na
      current. Ranolazine (Ran) is an antianginal drug acting on I(Na). After its
      current indication in the chronic stable angina, the role of this molecule is
      still being studied for prophylaxis of certain arrhythmias and treatment of heart
      failure. Moreover, have been recently developed new interesting patents of novel
      pharmaceutical effects and derivates of Ran.

PMID- 21867483
TI  - A critical role for citrate metabolism in LPS signalling.
AB  - Macrophage activation is a key event in the inflammatory process, since these
      cells produce a range of pro-inflammatory molecules, including ROS (reactive
      oxygen species), prostaglandins, cytokines and nitric oxide. These factors
      promote inflammation by causing vasodilation and recruitment of neutrophils,
      monocytes and lymphocytes, which ultimately clear infection and repair damaged
      tissue. One of the most potent macrophage activators is the Gram-negative-derived
      bacterial cell wall component LPS (lipopolysaccharide). LPS is sensed by TLR4
      (Toll-like receptor 4) and triggers highly complex signalling pathways that
      culminate in activation of transcription factors such as NF-kappaB (nuclear
      factor kappaB), which in turn increases transcription of genes encoding proteins
      such as COX2 (cyclo-oxygenase 2, a key enzyme in prostaglandin biosynthesis),
      nitric oxide synthase and cytokines such as TNF (tumour necrosis factor).
      Recently, a role for metabolic pathways in the regulation of LPS signalling has
      become a focus of research in inflammation. A notable example is LPS promoting
      the so-called Warburg effect - aerobic glycolysis. This allows for an up
      regulation in ATP production, and also for the production of biosynthetic
      intermediates to meet the demands of the activated macrophages. In this issue of
      the Biochemical Journal, Infantino et al. add a new finding to the role of
      metabolism in LPS action. They demonstrate a requirement for the mitochondrial
      citrate carrier in the induction of ROS, nitric oxide and prostaglandins by LPS.
      The knockdown of the carrier with siRNA (small interfering RNA), or the use of an
      inhibitor BTA (benzene-1,2,3-tricarboxylate), abolishes these responses. Although
      no mechanism is provided, the authors speculate that acetyl-CoA is synthesized
      from citrate in the cytosol. The acetyl-CoA generated could be required for
      phospholipid biosynthesis, the phospholipids being the source of arachidonic acid
      for prostaglandin production. Another product of citrate metabolism,
      oxaloacetate, will indirectly generate nitric oxide and ROS. This finding places
      citrate, transported from the mitochondria, as a key player in LPS signalling, at
      least for ROS, nitric oxide and prostaglandin production. This somewhat
      unexpected role for citrate in LPS action adds to a growing literature on the
      role for metabolism in the regulation of signalling in inflammation.

PMID- 21867484
TI  - Tetrahydrobiopterin: biochemistry and pathophysiology.
AB  - BH4 (6R-L-erythro-5,6,7,8-tetrahydrobiopterin) is an essential cofactor of a set
      of enzymes that are of central metabolic importance, including four aromatic
      amino acid hydroxylases, alkylglycerol mono-oxygenase and three NOS (NO synthase)
      isoenzymes. Consequently, BH4 is present in probably every cell or tissue of
      higher organisms and plays a key role in a number of biological processes and
      pathological states associated with monoamine neurotransmitter formation,
      cardiovascular and endothelial dysfunction, the immune response and pain
      sensitivity. BH4 is formed de novo from GTP via a sequence of three enzymatic
      steps carried out by GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase
      and sepiapterin reductase. An alternative or salvage pathway involves
      dihydrofolate reductase and may play an essential role in peripheral tissues.
      Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and
      dihydropteridine reductase, except for NOSs, in which the BH4 cofactor undergoes
      a one-electron redox cycle without the need for additional regeneration enzymes.
      With regard to the regulation of cofactor biosynthesis, the major controlling
      point is GTP cyclohydrolase I. BH4 biosynthesis is controlled in mammals by
      hormones and cytokines. BH4 deficiency due to autosomal recessive mutations in
      all enzymes, except for sepiapterin reductase, has been described as a cause of
      hyperphenylalaninaemia. A major contributor to vascular dysfunction associated
      with hypertension, ischaemic reperfusion injury, diabetes and others, appears to
      be an effect of oxidized BH4, which leads to an increased formation of oxygen
      derived radicals instead of NO by decoupled NOS. Furthermore, several
      neurological diseases have been suggested to be a consequence of restricted
      cofactor availability, and oral cofactor replacement therapy to stabilize mutant
      phenylalanine hydroxylase in the BH4-responsive type of hyperphenylalaninaemia
      has an advantageous effect on pathological phenylalanine levels in patients.

PMID- 21867485
TI  - Aggregation of amyloids in a cellular context: modelling and experiment.
AB  - Amyloid-related diseases are a group of illnesses in which an abnormal
      accumulation of proteins into fibrillar structures is evident. Results from a
      wide range of studies, ranging from identification of amyloid-beta dimers in the
      brain to biophysical characterization of the interactions between amyloidogenic
      peptides and lipid membranes during fibril growth shed light on the initial
      events which take place during amyloid aggregation. Accounts of fibril
      disaggregation and formation of globular aggregates due to interactions with
      lipids or fatty acids further demonstrate the complexity of the aggregation
      process and the difficulty to treat amyloid-related diseases. There is an
      inherent difficulty in generalizing from studies of aggregation in vitro, but the
      involvement of too many cellular components limits the ability to follow amyloid
      aggregation in a cellular (or extracellular) context. Fortunately, the
      development of experimental methods to generate stable globular aggregates
      suggests new means of studying the molecular events associated with amyloid
      aggregation. Furthermore, simulation studies enable deeper understanding of the
      experimental results and provide useful predictions that can be tested in the
      laboratory. Computer simulations can nowadays provide molecular or even atomistic
      details that are experimentally not available or very difficult to obtain. In the
      present review, recent developments on modelling and experiments of amyloid
      aggregation are reviewed, and an integrative account on how isolated interactions
      (as observed in vitro and in silico) combine during the course of amyloid-related
      diseases is presented. Finally, it is argued that an integrative approach is
      necessary to get a better understanding of the protein aggregation process.

PMID- 21867486
TI  - Emergence of quinolone resistance among extended-spectrum beta-lactamase
      producing Enterobacteriaceae in the Central African Republic: genetic
      characterization.
AB  - BACKGROUND: Cross-resistance to quinolones and beta-lactams is frequent in
      Enterobacteriaceae, due to the wide use of these antibiotics clinically and in
      the food industry. Prescription of one of these categories of antibiotic may
      consequently select for bacteria resistant to both categories. Genetic mechanisms
      of resistance may be secondary to a chromosomal mutation located in quinolone
      resistance determining region of DNA gyrase or topoisomerase IV or to a plasmid
      acquisition. The insertion sequence ISCR1 is often associated with qnr and may
      favour its dissemination in Gram-negative bacteria. The aim of this study was to
      determine the genetic mechanism of quinolone resistance among extended-spectrum
      beta-lactamase-producing Enterobacteriaceae strains in the Central African
      Republic. FINDINGS: Among seventeen ESBL-producing Enterobacteriaceae isolated
      from urine, pus or stool between January 2003 and October 2005 in the Central
      African Republic, nine were resistant to ciprofloxacin (seven from community
      patients and two from hospitalized patients). The ESBL were previously
      characterized as CTX-M-15 and SHV-12. Susceptibility to nalidixic acid,
      norfloxacin and ciprofloxacin, and the minimal inhibitory concentrations of these
      drugs were determined by disc diffusion and agar dilution methods, respectively.
      The presence of plasmid-borne ISCR1-qnrA region was determined by PCR and
      amplicons, if any, were sent for sequencing. Quinolone resistance determining
      region of DNA gyrase gyrA gene was amplified by PCR and then sequenced for
      mutation characterization. We found that all CTX-M-producing strains were
      resistant to the tested quinolones. All the isolates had the same nucleotide
      mutation at codon 83 of gyrA. Two Escherichia coli strains with the highest MICs
      were shown to harbour an ISCR1-qnrA1 sequence. This genetic association might
      favour dissemination of resistance to quinolone and perhaps other antibiotics
      among Enterobacteriaceae. CONCLUSIONS: This study shows that at least two
      mechanisms might explain the emerging resistance of Enterobacteriaceae to
      quinolones in the CAR. Beside the classical topoisomerase mutation, the cause may
      be acquisition of a plasmid-borne qnrA1. Clinicians and bacteriologists should be
      made aware of possible dissemination of ISCR1-qnrA1 among Enterobacteriacae.

PMID- 21867487
TI  - Increased performance uncertainty in children with ADHD? Elevated post-imperative
      negative variation (PINV) over the ventrolateral prefrontal cortex.
AB  - BACKGROUND: We aimed to investigate the influences of attention
      deficit/hyperactivity disorder (ADHD) on response evaluation, as reflected by the
      postimperative negative variation (PINV), a slow event-related potential.
      METHODS: We investigated PINV as an indicator of performance uncertainty in an
      audio-visual contingent negative variation (CNV) paradigm with an interstimulus
      interval of 3 seconds. A constant, unilateral, quick motor reaction with either
      the right or the left thumb was required after an auditory forewarned (S1) visual
      imperative stimulus (S2). We examined 18 ADHD patients (combined or hyperactive
      impulsive subtype) aged between 8 and 14 years and an age-, sex and IQ-matched
      control group of 19 healthy subjects using 64-channel high-density EEG. A first
      run was recorded drug-free, a second one under methylphenidate (MPH) medication
      in the ADHD group. RESULTS: We found a significantly increased negativity of the
      PINV-component over the ventrolateral prefrontal cortex in ADHD children compared
      to the healthy control group. PINV amplitude was influenced by movement side,
      most likely due to the slightly more difficult task when left hand responses were
      required. After the intake of MPH, PINV amplitudes of ADHD children normalized.
      CONCLUSIONS: We conclude that children with ADHD are likely to be more uncertain
      about the correctness of their performance and interpret the increased PINV as a
      hint towards compensatory mechanisms for a deficit in the evaluation of
      contingencies. Further studies are needed to assess the exact extent to which
      remainders of eye-movement related potentials contribute to PINV amplitude
      despite the correction for eye-artifacts.

PMID- 21867488
TI  - A multi-organ transcriptome resource for the Burmese Python (Python molurus
      bivittatus).
AB  - BACKGROUND: Snakes provide a unique vertebrate system for studying a diversity of
      extreme adaptations, including those related to development, metabolism,
      physiology, and venom. Despite their importance as research models, genomic
      resources for snakes are few. Among snakes, the Burmese python is the premier
      model for studying extremes of metabolic fluctuation and physiological
      remodelling. In this species, the consumption of large infrequent meals can
      induce a 40-fold increase in metabolic rate and more than a doubling in size of
      some organs. To provide a foundation for research utilizing the python, our aim
      was to assemble and annotate a transcriptome reference from the heart and liver.
      To accomplish this aim, we used the 454-FLX sequencing platform to collect
      sequence data from multiple cDNA libraries. RESULTS: We collected nearly 1
      million 454 sequence reads, and assembled these into 37,245 contigs with a
      combined length of 13,409,006 bp. To identify known genes, these contigs were
      compared to chicken and lizard gene sets, and to all Genbank sequences. A total
      of 13,286 of these contigs were annotated based on similarity to known genes or
      Genbank sequences. We used gene ontology (GO) assignments to characterize the
      types of genes in this transcriptome resource. The raw data, transcript contig
      assembly, and transcript annotations are made available online for use by the
      broader research community. CONCLUSION: These data should facilitate future
      studies using pythons and snakes in general, helping to further contribute to the
      utilization of snakes as a model evolutionary and physiological system. This
      sequence collection represents a major genomic resource for the Burmese python,
      and the large number of transcript sequences characterized should contribute to
      future research in this and other snake species.

PMID- 21867489
TI  - Rapidly growing left atrial myxoma: a case report.
AB  - INTRODUCTION: Left atrial myxomas are rare benign tumors of the heart. They vary
      widely in size, and very little is known about their growth rate. The reported
      growth rates of left atrial myxomas from several published case reports appears
      to vary from no growth, to between 1.3 to 6.9 mm/month in diameter within
      patients with established myxoma who have not undergone surgery. CASE
      PRESENTATION: We present the case of a rapidly growing pedunculated left atrial
      myxoma in a 62-year-old asymptomatic Caucasian woman found incidentally during
      routine transthoracic echocardiography. Our patient was attending her annual
      valve clinic assessment for moderate aortic regurgitation, and her two previous
      consecutive transthoracic echocardiography scans performed 12 and 24 months prior
      to this appointment had demonstrated a clear left atrium and aortic regurgitation
      of moderate severity. CONCLUSIONS: To the best of our knowledge, our case is the
      first to provide images of absence and presence of myxoma from transthoracic
      echocardiography scans taken a year apart, with estimated growth rate of 2.2
      mm/month. Rapidly growing myxoma may be mistaken for thrombus, and may require
      urgent surgical excision to reduce the risk of associated complications such as
      thrombo-embolic events, sudden cardiac death and removal of a possibly malignant
      tumor. The potential for rapid growth should be considered if there is a plan to
      delay surgery. Furthermore, it would be pertinent to consider annual
      echocardiography in patients presenting with clinical features suggestive of
      cardiac myxoma such as constitutional symptoms, as these tumors may be rapid
      growing and may only become apparent on subsequent echocardiography.

PMID- 21867490
TI  - Hands4U: a multifaceted strategy to implement guideline-based recommendations to
      prevent hand eczema in health care workers: design of a randomised controlled
      trial and (cost) effectiveness evaluation.
AB  - BACKGROUND: Workers in wet work occupations have a risk for developing hand
      eczema. Prevention strategies exist, but compliance to the proposed
      recommendations is poor. Therefore, a multifaceted implementation strategy (MIS)
      is developed to implement these recommendations to reduce hand eczema among
      health care workers performing wet work. METHODS/DESIGN: This study is a
      randomised controlled trial in three university hospitals in the Netherlands.
      Randomisation to the control or intervention group is performed at department
      level. The control group receives a leaflet containing the recommendations only.
      The intervention group receives the MIS which consists of five parts: 1) within a
      department, a participatory working group is formed to identify problems with the
      implementation of the recommendations, to find solutions for it and implement
      these solutions; 2) role models will help their colleagues in performing the
      desired behaviour; 3) education to all workers will enhance knowledge about (the
      prevention of) hand eczema; 4) reminders will be placed at the department
      reminding workers to use the recommendations; 5) workers receive the same leaflet
      as the control group containing the recommendations. Data are collected by
      questionnaires at baseline and after 3, 6, 9 and 12 months. The primary outcome
      measure is self-reported hand eczema. The most important secondary outcome
      measures are symptoms of hand eczema; actual use of the recommendations; sick
      leave; work productivity; and health care costs.Analyses will be performed
      according to the intention to treat principle. Cost-effectiveness of the MIS will
      be evaluated from both the societal and the employer's perspective. DISCUSSION:
      The prevention of hand eczema is important for the hospital environment. If the
      MIS has proven to be effective, a major improvement in the health of health care
      workers can be obtained. Results are expected in 2014. TRIAL REGISTRATION NUMBER:
      NTR2812.

PMID- 21867491
TI  - Multi-modality curative treatment of salivary gland cancer liver metastases with
      drug-eluting bead chemoembolization, radiofrequency ablation, and surgical
      resection: a case report.
AB  - INTRODUCTION: Liver metastases are rare in salivary gland tumors and have been
      reported only once to be the first manifestation of the disease. They are usually
      treated with surgical resection of the primary tumor and systemic chemotherapy.
      Drug-eluting bead chemoembolization has an evolving role in the treatment of
      hepatocellular carcinoma, as well as in the treatment of metastatic disease of
      the liver. Nevertheless, it has never been used in a patient with salivary gland
      liver metastases. CASE PRESENTATION: We report a case of a 51-year-old Caucasian
      Greek woman who presented to our hospital with liver metastases as the first
      manifestation of an adenoid cystic carcinoma of the left submandibular gland. The
      liver lesions were deemed inoperable because of their size and multi-focality and
      proved resistant to systemic chemotherapy. She was curatively treated with a
      combination of doxorubicin eluting bead (DC Beads) chemoembolization, intra
      operative and percutaneous radiofrequency ablation, and radiofrequency-assisted
      surgical resection. The patient remained disease-free one year after the surgical
      resection. CONCLUSION: In conclusion, this complex case is an example of
      inoperable liver metastatic disease from the salivary glands that was refractory
      to systemic chemotherapy but was curatively treated with a combination of
      locoregional therapies and surgery. A multi-disciplinary approach and the
      adoption of modern radiological techniques produced good results after
      conventional therapies failed and there were no other available treatment
      modalities.

PMID- 21867492
TI  - Cost-effectiveness of a mailed educational reminder to increase colorectal cancer
      screening.
AB  - BACKGROUND: Colorectal cancer (CRC) screening rates are low in many areas and
      cost-effective interventions to promote CRC screening are needed. Recently in a
      randomized controlled trial, a mailed educational reminder increased CRC
      screening rates by 16.2% among U.S. Veterans. The aim of our study was to assess
      the costs and cost-effectiveness of a mailed educational reminder on fecal occult
      blood test (FOBT) adherence. METHODS: In a blinded, randomized, controlled trial,
      769 patients were randomly assigned to the usual care group (FOBT alone, n = 382)
      or the intervention group (FOBT plus a mailed reminder, n = 387). Ten days after
      picking up the FOBT cards, a 1-page reminder with information related to CRC
      screening was mailed to the intervention group. Primary outcome was number of
      returned FOBT cards after 6 months. The costs and incremental cost-effectiveness
      ratio (ICER) of the intervention were assessed and calculated respectively.
      Sensitivity analyses were based on varying costs of labor and supplies. RESULTS:
      At 6 months after card distribution, 64.6% patients in the intervention group
      returned FOBT cards compared with 48.4% in the control group (P < 0.001). The
      total cost of the intervention was $962 or $2.49 per patient, and the ICER was
      $15 per additional person screened for CRC. Sensitivity analysis based on a 10%
      cost variation was $13.50 to $16.50 per additional patient screened for CRC.
      CONCLUSIONS: A simple mailed educational reminder increases FOBT card return rate
      at a cost many health care systems can afford. Compared to other patient-directed
      interventions (telephone, letters from physicians, mailed reminders) for CRC
      screening, our intervention was more effective and cost-effective.

PMID- 21867493
TI  - P53 suppresses expression of the 14-3-3 gamma oncogene.
AB  - BACKGROUND: 14-3-3 proteins are a family of highly conserved proteins that are
      involved in a wide range of cellular processes. Recent evidence indicates that
      some of these proteins have oncogenic activity and that they may promote
      tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3
      gamma, is over expressed in human lung cancers and that it can induce
      transformation of rodent cells in vitro. METHODS: qRTPCR and Western blot
      analysis were performed to examine 14-3-3 gamma expression in non-small cell lung
      cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were
      detected by direct sequencing and also by western blot. CHIP and yeast one hybrid
      assays were used to detect p53 binding to 14-3-3 gamma promoter. RESULTS:
      Quantitative rtPCR results showed that the expression level of 14-3-3 gamma was
      elevated in the majority of NSCLC that we examined which was also consistent with
      protein expression. Further analysis of the expression pattern of 14-3-3 gamma in
      lung tumors showed a correlation with p53 mutations suggesting that p53 might
      suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence
      revealed the presence of a p53 consensus binding motif and in vitro assays
      demonstrated that wild-type p53 bound to this motif when activated by ionizing
      radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress
      14-3-3 gamma expression. CONCLUSION: Increased expression of 14-3-3 gamma in lung
      cancer coincides with loss of functional p53. Hence, we propose that 14-3-3
      gamma's oncogenic activities cooperate with loss of p53 to promote lung
      tumorigenesis.

PMID- 21867494
TI  - Correction: The Fabrication of Nano-Particles in aqueous solution from
      Oxyfluoride Glass Ceramics by Thermal Induction and Corrosion Treatment.

PMID- 21867495
TI  - Can we make the basilic vein larger? maneuvers to facilitate ultrasound guided
      peripheral intravenous access: a prospective cross-sectional study.
AB  - BACKGROUND: Studies have shown that vein size is an important predictor of
      successful ultrasound-guided vascular access. The objective of this study is to
      evaluate maneuvers designed to increase basilic vein size, which could be used to
      facilitate ultrasound-guided peripheral intravenous access (USGPIV) in the
      Emergency Department (ED) setting. METHODS: This was a prospective non-randomized
      trial. Healthy volunteers aged 18-65 were enrolled. Basilic veins were identified
      and the cross-sectional area measured sonographically. Following baseline
      measurement, the following maneuvers were performed: application of a tourniquet,
      inflation of a blood pressure (BP) cuff, application of a tourniquet with the arm
      lowered, and BP cuff inflation with the arm lowered. Following each maneuver
      there was 30 s of recovery time, and a baseline measurement was repeated to
      ensure that the vein had returned to baseline. Change in basilic vein size was
      modeled using mixed model analysis with a Tukey correction for multiple
      comparisons to determine if significant differences existed between different
      maneuvers. RESULTS: Over the 5-month study period, 96 basilic veins were assessed
      from 52 volunteers. All of the maneuvers resulted in a statistically significant
      increase in basilic vein size from baseline (p < 0.001). BP cuff inflation had
      the greatest increase in vein size from baseline 17%, 0.87 mm 95% CI (0.70-1.04).
      BP cuff inflation statistically significantly increased vein size compared to
      tourniquet placement by 3%, 0.16 mm 95% CI (0.02-0.30). CONCLUSIONS: The largest
      increase in basilic vein size was due to blood pressure cuff inflation. BP cuff
      inflation resulted in a statistically significant increase in vein size compared
      to tourniquet application, but this difference may not be clinically significant.

PMID- 21867496
TI  - Exploiting bounded signal flow for graph orientation based on cause-effect pairs.
AB  - BACKGROUND: We consider the following problem: Given an undirected network and a
      set of sender-receiver pairs, direct all edges such that the maximum number of
      "signal flows" defined by the pairs can be routed respecting edge directions.
      This problem has applications in understanding protein interaction based cell
      regulation mechanisms. Since this problem is NP-hard, research so far
      concentrated on polynomial-time approximation algorithms and tractable special
      cases. RESULTS: We take the viewpoint of parameterized algorithmics and examine
      several parameters related to the maximum signal flow over vertices or edges. We
      provide several fixed-parameter tractability results, and in one case a sharp
      complexity dichotomy between a linear-time solvable case and a slightly more
      general NP-hard case. We examine the value of these parameters for several real
      world network instances. CONCLUSIONS: Several biologically relevant special cases
      of the NP-hard problem can be solved to optimality. In this way, parameterized
      analysis yields both deeper insight into the computational complexity and
      practical solving strategies.

PMID- 21867497
TI  - GPs' opinions of public and industrial information regarding drugs: a cross
      sectional study.
AB  - BACKGROUND: General Practitioners {GP} in Sweden prescribe more than 50% of all
      prescriptions. Scientific knowledge on the opinions of GPs regarding drug
      information has been sparse. Such knowledge could be valuable when designing
      evidence-based drug information to GPs. GPs' opinions on public- and industry
      provided drug information are presented in this article. METHODS: A cross
      sectional study using a questionnaire was answered by 368 GPs at 97 primary
      health care centres {PHCC}. The centres were invited to participate by eight out
      of 29 drug and therapeutic committees {DTCs}. A multilevel model was used to
      analyse associations between opinions of GPs regarding drug information and
      whether the GPs worked in public sector or in a private enterprise, their age,
      sex, and work experience. PHCC and geographical area were included as random
      effects. RESULTS: About 85% of the GPs perceived they received too much
      information from the industry, that the quality of public information was high
      and useful, and that the main task of public authorities was to increase the GPs'
      knowledge of drugs. Female GPs valued information from public authorities to a
      much greater extent than male GPs. Out of the GPs, 93% considered the main task
      of the industry was to promote sales. Differences between the GPs' opinions
      between PHCCs were generally more visible than differences between areas.
      CONCLUSIONS: Some kind of incentives could be considered for PHCCs that actively
      reduce drug promotion from the industry. That female GPs valued information from
      public authorities to a much greater extent than male GPs should be taken into
      consideration when designing evidence-based drug information from public
      authorities to make implementation easier.

PMID- 21867498
TI  - Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel
      exhaust particles in rat brain microvessels.
AB  - BACKGROUND: AhR activates the transcription of several target genes including
      CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme
      expressed in human brain microvessels. Here, we studied the effect of AhR
      activation by environmental pollutants on the expression of Cyp1b1 in rat brain
      microvessels. METHODS: Expression of AhR and Cyp1b1 was detected in isolated rat
      brain microvessels. AhR was immunovisualised in brain microvessel endothelial
      cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated
      brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy
      hydrocarbons containing diesel exhaust particles (DEP) or Delta9
      tetrahydrocannabinol (Delta9-THC). RESULTS: After ex vivo exposure to TCDD (a
      highly potent AhR ligand) for 3 h, Cyp1b1 expression was significantly increased
      by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased
      Cyp1b1 transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain
      microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo)
      strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1
      induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist.
      In contrast, a sub-chronic in vivo treatment with Delta9-THC once daily for 7
      seven days had no effect on Cyp1b1 expression CONCLUSIONS: Our results show that
      TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through
      AhR activation.

PMID- 21867500
TI  - Creating a knowledge translation trainee collaborative: from conceptualization to
      lessons learned in the first year.
AB  - Trainees (e.g., graduate students, residents, fellows) are increasingly
      identifying knowledge translation as their research discipline. In Canada, a
      group of trainees have created a trainee-initiated and trainee-led national
      collaborative to provide a vehicle for trainees to examine the diversity of
      knowledge translation research and practice, and to link trainees from diverse
      geographical areas and disciplines. The aim of this paper is to describe our
      experience and lessons learned in creating the Knowledge Translation Trainee
      Collaborative. In this meeting report, we outline the process, challenges, and
      opportunities in planning and experiencing the collaborative's inaugural meeting
      as participant organizers, and present outcomes and learnings to date.

PMID- 21867499
TI  - Sex differences in resting hemodynamics and arterial stiffness following 4 weeks
      of resistance versus aerobic exercise training in individuals with pre
      hypertension to stage 1 hypertension.
AB  - BACKGROUND: Hypertension (HTN) exhibits sexual dimorphism; the incidence for
      women surpasses men during the sixth decade of life, while the pharmacological
      treatments are less effective and produce more side-effects in women than in men.
      Aerobic exercise (AE) has been shown to prevent and treat HTN; however,
      resistance exercise (RE) is not recommended as a strategy to treat HTN. In this
      study, we investigated the potential sex differences of AE versus RE in a cohort
      of unmedicated patients with hypertension. METHODS: In total, 40 moderately
      active, pre-hypertensive or stage 1 essential hypertensive male (M) and female
      (F) participants aged 40 to 60 years were randomly divided into four groups: M
      AE, M RE, F AE, and F. Each group exercised at moderate intensity, 3 days/week
      for 4 weeks. Hemodynamic, vascular and blood-flow data were collected before and
      after exercise training. RESULTS: Men showed a significant increase in central
      pulse wave velocity following RE while females showed no significant changes (12
      +/- to 13.9 +/- vs. 9.2 +/- to 9.6 +/- m/s, respectively). RE showed
      significantly greater increases in peak blood flow when compared to AE (F RE 15
      +/- to 20 +/- vs. F AE 17.5 +/- to19.5 +/-, M RE 19 +/- to 24 +/- vs M AE 21 +/-
      to 25 +/- ml* 100 ml*min, respectively). In addition, systolic and diastolic BP
      decreased greater for women following RE when compared to AE whereas men showed
      comparable decreases in BP following either exercise mode. CONCLUSION: Moderate
      intensity RE training may be a more favorable for women as a treatment option for
      hypertension because of greater decreases in diastolic BP and significant
      increases in flow-mediated dilation without concomitant increases in arterial
      stiffness, compared with their male counterparts.

PMID- 21867501
TI  - Municipal bylaw to reduce cosmetic/non-essential pesticide use on household lawns
      - a policy implementation evaluation.
AB  - BACKGROUND: Pesticide use on urban lawns and gardens contributes to environmental
      contamination and human exposure. Municipal policies to restrict use and educate
      households on viable alternatives deserve study. We describe the development and
      implementation of a cosmetic/non-essential pesticide bylaw by a municipal health
      department in Toronto, Ontario, Canada and assess changes in resident practices
      associated with bylaw implementation. METHODS: Implementation indicators built on
      a logic model and were elaborated through key informant interviews. Bylaw impacts
      on awareness and practice changes were documented through telephone surveys
      administered seasonally pre, during and post implementation (2003-2008).
      Multivariable logistic regression models assessed associations of demographic
      variables and gardening season with respondent awareness and practices. RESULTS:
      Implementation indicators documented multiple municipal health department
      activities and public involvement in complaints from commencement of the
      educational phase. During the enforcement phases only 40 warning letters and 7
      convictions were needed. The number of lawn care companies increased. Among
      survey respondents, awareness of the bylaw and the Natural Lawn campaign reached
      69% and 76% respectively by 2008. Substantial decreases in the proportion of
      households applying pesticides (25 to 11%) or hiring lawn care companies for
      application (15 to 5%) occurred. Parallel absolute increases in use of natural
      lawn care methods occurred among households themselves (21%) and companies they
      contracted (7%). CONCLUSIONS: Bylaws or ordinances implemented through education
      and enforcement are a viable policy option for reducing urban cosmetic pesticide
      use.

PMID- 21867502
TI  - Standard versus prosocial online support groups for distressed breast cancer
      survivors: a randomized controlled trial.
AB  - BACKGROUND: The Internet can increase access to psychosocial care for breast
      cancer survivors through online support groups. This study will test a novel
      prosocial online group that emphasizes both opportunities for getting and giving
      help. Based on the helper therapy principle, it is hypothesized that the addition
      of structured helping opportunities and coaching on how to help others online
      will increase the psychological benefits of a standard online group.
      METHODS/DESIGN: A two-armed randomized controlled trial with pretest and
      posttest. Non-metastatic breast cancer survivors with elevated psychological
      distress will be randomized to either a standard facilitated online group or to a
      prosocial facilitated online group, which combines online exchanges of support
      with structured helping opportunities (blogging, breast cancer outreach) and
      coaching on how best to give support to others. Validated and reliable measures
      will be administered to women approximately one month before and after the
      interventions. Self-esteem, positive affect, and sense of belonging will be
      tested as potential mediators of the primary outcomes of depressive/anxious
      symptoms and sense of purpose in life. DISCUSSION: This study will test an
      innovative approach to maximizing the psychological benefits of cancer online
      support groups. The theory-based prosocial online support group intervention
      model is sustainable, because it can be implemented by private non-profit or
      other organizations, such as cancer centers, which mostly offer face-to-face
      support groups with limited patient reach. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01396174.

PMID- 21867503
TI  - Pharmacological effects of Radix Angelica Sinensis (Danggui) on cerebral
      infarction.
AB  - Radix Angelica Sinensis, the dried root of Angelica sinensis (Danggui), is a
      herb used in Chinese medicine to enrich blood, promote blood circulation and
      modulate the immune system. It is also used to treat chronic constipation of the
      elderly and debilitated as well as menstrual disorders. Research has demonstrated
      that Danggui and its active ingredients, as anti-arthrosclerotic, anti
      hypertensive, antioxidant anti-inflammatory agents which would limit platelet
      aggregation, are effective in reducing the size of cerebral infarction and
      improving neurological deficit scores.

PMID- 21867504
TI  - Translation and manipulation of silicon nanomembranes using holographic optical
      tweezers.
AB  - We demonstrate the use of holographic optical tweezers for trapping and
      manipulating silicon nanomembranes. These macroscopic free-standing sheets of
      single-crystalline silicon are attractive for use in next-generation flexible
      electronics. We achieve three-dimensional control by attaching a functionalized
      silica bead to the silicon surface, enabling non-contact trapping and
      manipulation of planar structures with high aspect ratios (high lateral size to
      thickness). Using as few as one trap and trapping powers as low as several
      hundred milliwatts, silicon nanomembranes can be rotated and translated in a
      solution over large distances.

PMID- 21867505
TI  - Functionalised graphene sheets as effective high dielectric constant fillers.
AB  - A new functionalised graphene sheet (FGS) filled poly(dimethyl)siloxane
      insulator nanocomposite has been developed with high dielectric constant, making
      it well suited for applications in flexible electronics. The dielectric
      permittivity increased tenfold at 10 Hz and 2 wt.% FGS, while preserving low
      dielectric losses and good mechanical properties. The presence of functional
      groups on the graphene sheet surface improved the compatibility
      nanofiller/polymer at the interface, reducing the polarisation process. This
      study demonstrates that functionalised graphene sheets are ideal nanofillers for
      the development of new polymer composites with high dielectric constant
      values.PACS: 78.20.Ci, 72.80.Tm, 62.23.Kn.

PMID- 21867506
TI  - Molecular targeting of prostate cancer cells by a triple drug combination down
      regulates integrin driven adhesion processes, delays cell cycle progression and
      interferes with the cdk-cyclin axis.
AB  - BACKGROUND: Single drug use has not achieved satisfactory results in the
      treatment of prostate cancer, despite application of increasingly widespread
      targeted therapeutics. In the present study, the combined impact of the mammalian
      target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine
      kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic
      acid (VPA) on prostate cancer growth and adhesion in vitro was investigated.
      METHODS: PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or
      with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and
      cell cycle regulating proteins were then investigated by MTT-assay, flow
      cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to
      vascular endothelium or to immobilized extracellular matrix proteins as well as
      migratory properties of the cells was evaluated, and integrin alpha and beta
      subtypes were analyzed. Finally, effects of drug treatment on cell signaling
      pathways were determined. RESULTS: All drugs, separately applied, reduced tumor
      cell adhesion, migration and growth. A much stronger anti-cancer effect was
      evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B
      were reduced, whereas p27 was elevated. In addition, simultaneous application of
      RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression
      pattern of various integrin alpha and beta subtypes, reduced integrin-linked
      kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis
      revealed that EGFr and the downstream target Akt, as well as p70S6k was
      distinctly modified in the presence of the drug combination. CONCLUSIONS:
      Simultaneous targeting of several key proteins in prostate cancer cells provides
      an advantage over targeting a single pathway. Since strong anti-tumor properties
      became evident with respect to cell growth and adhesion dynamics, the triple drug
      combination might provide progress in the treatment of advanced prostate cancer.

PMID- 21867507
TI  - The glutamine synthetase gene family in Populus.
AB  - BACKGROUND: Glutamine synthetase (GS; EC: 6.3.1.2, L-glutamate: ammonia ligase
      ADP-forming) is a key enzyme in ammonium assimilation and metabolism of higher
      plants. The current work was undertaken to develop a more comprehensive
      understanding of molecular and biochemical features of GS gene family in poplar,
      and to characterize the developmental regulation of GS expression in various
      tissues and at various times during the poplar perennial growth. RESULTS: The GS
      gene family consists of 8 different genes exhibiting all structural and
      regulatory elements consistent with their roles as functional genes. Our results
      indicate that the family members are organized in 4 groups of duplicated genes, 3
      of which code for cytosolic GS isoforms (GS1) and 1 which codes for the
      choroplastic GS isoform (GS2). Our analysis shows that Populus trichocarpa is the
      first plant species in which it was observed the complete GS family duplicated.
      Detailed expression analyses have revealed specific spatial and seasonal patterns
      of GS expression in poplar. These data provide insights into the metabolic
      function of GS isoforms in poplar and pave the way for future functional studies.
      CONCLUSIONS: Our data suggest that GS duplicates could have been retained in
      order to increase the amount of enzyme in a particular cell type. This
      possibility could contribute to the homeostasis of nitrogen metabolism in
      functions associated to changes in glutamine-derived metabolic products. The
      presence of duplicated GS genes in poplar could also contribute to
      diversification of the enzymatic properties for a particular GS isoform through
      the assembly of GS polypeptides into homo oligomeric and/or hetero oligomeric
      holoenzymes in specific cell types.

PMID- 21867508
TI  - Production of silk sericin/silk fibroin blend nanofibers.
AB  - Silk sericin (SS)/silk fibroin (SF) blend nanofibers have been produced by
      electrospinning in a binary SS/SF trifluoroacetic acid (TFA) solution system,
      which was prepared by mixing 20 wt.% SS TFA solution and 10 wt.% SF TFA solution
      to give different compositions. The diameters of the SS/SF nanofibers ranged from
      33 to 837 nm, and they showed a round cross section. The surface of the SS/SF
      nanofibers was smooth, and the fibers possessed a bead-free structure. The
      average diameters of the SS/SF (75/25, 50/50, and 25/75) blend nanofibers were
      much thicker than that of SS and SF nanofibers. The SS/SF (100/0, 75/25, and
      50/50) blend nanofibers were easily dissolved in water, while the SS/SF (25/75
      and 0/100) blend nanofibers could not be completely dissolved in water. The SS/SF
      blend nanofibers could not be completely dissolved in methanol. The SS/SF blend
      nanofibers were characterized by Fourier transform infrared (FTIR) spectroscopy,
      differential scanning calorimetry, and differential thermal analysis. FTIR showed
      that the SS/SF blend nanofibers possessed a random coil conformation and beta
      sheet structure.

PMID- 21867509
TI  - Cancer as a dynamical phase transition.
AB  - This paper discusses the properties of cancer cells from a new perspective based
      on an analogy with phase transitions in physical systems. Similarities in terms
      of instabilities and attractor states are outlined and differences discussed.
      While physical phase transitions typically occur at or near thermodynamic
      equilibrium, a normal-to-cancer (NTC) transition is a dynamical non-equilibrium
      phenomenon, which depends on both metabolic energy supply and local physiological
      conditions. A number of implications for preventative and therapeutic strategies
      are outlined.

PMID- 21867510
TI  - Vertical decomposition with Genetic Algorithm for Multiple Sequence Alignment.
AB  - BACKGROUND: Many Bioinformatics studies begin with a multiple sequence alignment
      as the foundation for their research. This is because multiple sequence alignment
      can be a useful technique for studying molecular evolution and analyzing sequence
      structure relationships. RESULTS: In this paper, we have proposed a Vertical
      Decomposition with Genetic Algorithm (VDGA) for Multiple Sequence Alignment
      (MSA). In VDGA, we divide the sequences vertically into two or more subsequences,
      and then solve them individually using a guide tree approach. Finally, we combine
      all the subsequences to generate a new multiple sequence alignment. This
      technique is applied on the solutions of the initial generation and of each child
      generation within VDGA. We have used two mechanisms to generate an initial
      population in this research: the first mechanism is to generate guide trees with
      randomly selected sequences and the second is shuffling the sequences inside such
      trees. Two different genetic operators have been implemented with VDGA. To test
      the performance of our algorithm, we have compared it with existing well-known
      methods, namely PRRP, CLUSTALX, DIALIGN, HMMT, SB_PIMA, ML_PIMA, MULTALIGN, and
      PILEUP8, and also other methods, based on Genetic Algorithms (GA), such as SAGA,
      MSA-GA and RBT-GA, by solving a number of benchmark datasets from BAliBase 2.0.
      CONCLUSIONS: The experimental results showed that the VDGA with three vertical
      divisions was the most successful variant for most of the test cases in
      comparison to other divisions considered with VDGA. The experimental results also
      confirmed that VDGA outperformed the other methods considered in this research.

PMID- 21867511
TI  - Parallelized short read assembly of large genomes using de Bruijn graphs.
AB  - BACKGROUND: Next-generation sequencing technologies have given rise to the
      explosive increase in DNA sequencing throughput, and have promoted the recent
      development of de novo short read assemblers. However, existing assemblers
      require high execution times and a large amount of compute resources to assemble
      large genomes from quantities of short reads. RESULTS: We present PASHA, a
      parallelized short read assembler using de Bruijn graphs, which takes advantage
      of hybrid computing architectures consisting of both shared-memory multi-core
      CPUs and distributed-memory compute clusters to gain efficiency and scalability.
      Evaluation using three small-scale real paired-end datasets shows that PASHA is
      able to produce more contiguous high-quality assemblies in shorter time compared
      to three leading assemblers: Velvet, ABySS and SOAPdenovo. PASHA's scalability
      for large genome datasets is demonstrated with human genome assembly. Compared to
      ABySS, PASHA achieves competitive assembly quality with faster execution speed on
      the same compute resources, yielding an NG50 contig size of 503 with the longest
      correct contig size of 18,252, and an NG50 scaffold size of 2,294. Moreover, the
      human assembly is completed in about 21 hours with only modest compute resources.
      CONCLUSIONS: Developing parallel assemblers for large genomes has been garnering
      significant research efforts due to the explosive size growth of high-throughput
      short read datasets. By employing hybrid parallelism consisting of multi
      threading on multi-core CPUs and message passing on compute clusters, PASHA is
      able to assemble the human genome with high quality and in reasonable time using
      modest compute resources.

PMID- 21867512
TI  - Cognitive function among hemodialysis patients in Japan.
AB  - BACKGROUND: Over 290,000 patients are undergoing hemodialysis (HD) in Japan. With
      old age, the odds of undergoing HD treatment sharply increase, as does the
      prevalence of cognitive impairment. The aim of the present work was to assess
      cognitive impairment in HD patients and its relation to clinical characteristics.
      METHODS: Using a cross-sectional design, we administered the Mini-Mental State
      Examination (MMSE) to 154 HD outpatients and 852 participants from the Iwaki
      Health Promotion Project 2010, representing the general population. RESULTS: The
      prevalence of cognitive impairment based on the MMSE was 18.8% in HD patients. HD
      patients showed a higher prevalence of cognitive impairment in older groups (50
      years and older). In a logistic regression model with age, gender and amount of
      education as covariates, undergoing HD was a significant independent factor (OR =
      2.28, 95% CI 1.33 to 3.94) associated with a lower MMSE score. Among HD patients,
      we found that level of education was associated with MMSE score. CONCLUSIONS:
      There is a high prevalence of cognitive impairment among HD patients that has
      adverse implications for hospitalization and shortens their life expectancy. HD
      treatment was an independent risk factor for cognitive impairment. Clinicians
      should carefully monitor and treat cognitive impairment in HD patients. Further
      studies are required to determine the reasons for cognitive impairment in HD
      patients.

PMID- 21867513
TI  - Factors affecting residency rank-listing: a Maxdiff survey of graduating Canadian
      medical students.
AB  - BACKGROUND: In Canada, graduating medical students consider many factors,
      including geographic, social, and academic, when ranking residency programs
      through the Canadian Residency Matching Service (CaRMS). The relative
      significance of these factors is poorly studied in Canada. It is also unknown how
      students differentiate between their top program choices. This survey study
      addresses the influence of various factors on applicant decision making. METHODS:
      Graduating medical students from all six Ontario medical schools were invited to
      participate in an online survey available for three weeks prior to the CaRMS
      match day in 2010. Max-Diff discrete choice scaling, multiple choice, and drop
      list style questions were employed. The Max-Diff data was analyzed using a scaled
      simple count method. Data for how students distinguish between top programs was
      analyzed as percentages. Comparisons were made between male and female applicants
      as well as between family medicine and specialist applicants; statistical
      significance was determined by the Mann-Whitney test. RESULTS: In total, 339 of
      819 (41.4%) eligible students responded. The variety of clinical experiences and
      resident morale were weighed heavily in choosing a residency program; whereas
      financial incentives and parental leave attitudes had low influence. Major
      reasons that applicants selected their first choice program over their second
      choice included the distance to relatives and desirability of the city. Both
      genders had similar priorities when selecting programs. Family medicine
      applicants rated the variety of clinical experiences more importantly; whereas
      specialty applicants emphasized academic factors more. CONCLUSIONS: Graduating
      medical students consider program characteristics such as the variety of clinical
      experiences and resident morale heavily in terms of overall priority. However,
      differentiation between their top two choice programs is often dependent on
      social/geographic factors. The results of this survey will contribute to a better
      understanding of the CaRMS decision making process for both junior medical
      students and residency program directors.

PMID- 21867515
TI  - Simple parametric survival analysis with anonymized register data: A cohort study
      with truncated and interval censored event and censoring times.
AB  - BACKGROUND: To preserve patient anonymity, health register data may be provided
      as binned data only. Here we consider as example, how to estimate mean survival
      time after a diagnosis of metastatic colorectal cancer from Norwegian register
      data on time to death or censoring binned into 30 day intervals. All events
      occurring in the first three months (90 days) after diagnosis were removed to
      achieve comparability with a clinical trial. The aim of the paper is to develop
      and implement a simple, and yet flexible method for analyzing such interval
      censored and truncated data. METHODS: Considering interval censoring a missing
      data problem, we implement a simple multiple imputation strategy that allows
      flexible sensitivity analyses with respect to the shape of the censoring
      distribution. To allow identification of appropriate parametric models, a chi2
      goodness-of-fit test--also imputation based--is derived and supplemented with
      diagnostic plots. Uncertainty estimates for mean survival times are obtained via
      a simulation strategy. The validity and statistical efficiency of the proposed
      method for varying interval lengths is investigated in a simulation study and
      compared with simpler alternatives. RESULTS: Mean survival times estimated from
      the register data ranged from 1.2 (SE = 0.09) to 3.2 (0.31) years depending on
      period of diagnosis and choice of parametric model. The shape of the censoring
      distribution within intervals did generally not influence results, whereas the
      choice of parametric model did, even when different models fit the data equally
      well. In simulation studies both simple midpoint imputation and multiple
      imputation yielded nearly unbiased analyses (relative biases of -0.6% to 9.4%)
      and confidence intervals with near-nominal coverage probabilities (93.4% to
      95.7%) for censoring intervals shorter than six months. For 12 month censoring
      intervals, multiple imputation provided better protection against bias, and
      coverage probabilities closer to nominal values than simple midpoint imputation.
      CONCLUSION: Binning of event and censoring times should be considered a viable
      strategy for anonymizing register data on survival times, as they may be readily
      analyzed with methods based on multiple imputation.

PMID- 21867514
TI  - MicroRNAs coordinately regulate protein complexes.
AB  - BACKGROUND: In animals, microRNAs (miRNAs) regulate the protein synthesis of
      their target messenger RNAs (mRNAs) by either translational repression or
      deadenylation. miRNAs are frequently found to be co-expressed in different
      tissues and cell types, while some form polycistronic clusters on genomes.
      Interactions between targets of co-expressed miRNAs (including miRNA clusters)
      have not yet been systematically investigated. RESULTS: Here we integrated
      information from predicted and experimentally verified miRNA targets to
      characterize protein complex networks regulated by human miRNAs. We found
      striking evidence that individual miRNAs or co-expressed miRNAs frequently target
      several components of protein complexes. We experimentally verified that the miR
      141-200c cluster targets different components of the CtBP/ZEB complex, suggesting
      a potential orchestrated regulation in epithelial to mesenchymal transition.
      CONCLUSIONS: Our findings indicate a coordinate posttranscriptional regulation of
      protein complexes by miRNAs. These provide a sound basis for designing
      experiments to study miRNA function at a systems level.

PMID- 21867516
TI  - Improved specificity for detection of Mycobacterium bovis in fresh tissues using
      IS6110 real-time PCR.
AB  - BACKGROUND: Culture of M. bovis from diagnostic specimens is the gold standard
      for bovine tuberculosis diagnostics in the USA. Detection of M. bovis by PCR in
      tissue homogenates may provide a simple rapid method to complement bacterial
      culture. A significant impediment to PCR based assays on tissue homogenates is
      specificity since mycobacteria other than M. bovis may be associated with the
      tissues. RESULTS: Previously published IS6110 based PCR diagnostic assays, along
      with one developed in house, were tested against environmental mycobacteria
      commonly isolated from diagnostic tissues submitted to the National Veterinary
      Services Laboratory. A real-time PCR assay was developed (IS6110_T) that had
      increased specificity over other IS6110 based assays. Of the 13 non-tuberculous
      mycobacteria tested with IS6110_T only M. wolinskyi was positive. Thirty M. bovis
      infected tissue homogenates and 18 control tissues were used to evaluate the
      potential for the assay as a diagnostic test. In this small sample, IS6110_T
      detected 20/30 samples from M. bovis infected animals and 0/18 control tissues.
      CONCLUSIONS: The IS6110_T assay provides a PCR based assay system that is
      compatible with current diagnostic protocols for the detection of M. bovis in the
      USA and compliments current testing strategies.

PMID- 21867517
TI  - Determinants of self-rated health in old age: a population-based, cross-sectional
      study using the International Classification of Functioning.
AB  - BACKGROUND: Self-rated health (SRH) is a widely used indicator of general health
      and multiple studies have supported the predictive validity of SRH in older
      populations concerning future health, functional decline, disability, and
      mortality. The aim of this study was to use the theoretical framework of the
      International Classification of Functioning, Disability and Health (ICF) to
      create a better understanding of factors associated with SRH among community
      dwelling older people in urban and rural areas. METHODS: The study design was
      population-based and cross-sectional. Participants were 185 Icelanders, randomly
      selected from a national registry, community-dwelling, 65-88 years old, 63% urban
      residents, and 52% men. Participants were asked: "In general, would you say your
      health is excellent, very good, good, fair, or poor?" Associations with SRH were
      analyzed with ordinal logistic regression. Explanatory variables represented
      aspects of body functions, activities, participation, environmental factors and
      personal factors components of the ICF. RESULTS: Univariate analysis revealed
      that SRH was significantly associated with all analyzed ICF components through 16
      out of 18 explanatory variables. Multivariate analysis, however, demonstrated
      that SRH had an independent association with five variables representing ICF body
      functions, activities, and personal factors components: The likelihood of a
      better SRH increased with advanced lower extremity capacity (adjusted odds ratio
      [adjOR] = 1.05, p < 0.001), upper extremity capacity (adjOR = 1.13, p = 0.040),
      household physical activity (adjOR = 1.01, p = 0.016), and older age (adjOR =
      1.09, p = 0.006); but decreased with more depressive symptoms (adjOR = 0.79, p <
      0.001). CONCLUSIONS: The results highlight a collection of ICF body functions,
      activities and personal factors associated with higher SRH among community
      dwelling older people. Some of these, such as physical capacity, depressive
      symptoms, and habitual physical activity are of particular interest due to their
      potential for change through public health interventions. The use of ICF
      conceptual framework and widely accepted standardized assessments should make
      these results comparable and relevant in an international context.

PMID- 21867518
TI  - Prevalence and correlates of HIV, syphilis, and hepatitis B and C infection and
      harm reduction program use among male injecting drug users in Kabul, Afghanistan:
      A cross-sectional assessment.
AB  - BACKGROUND: A nascent HIV epidemic and high prevalence of risky drug practices
      were detected among injecting drug users (IDUs) in Kabul, Afghanistan from 2005
      2006. We assessed prevalence of HIV, hepatitis C virus (HCV), hepatitis B surface
      antigen (HBsAg), syphilis, and needle and syringe program (NSP) use among this
      population. METHODS: IDUs were recruited between June, 2007 and March, 2009 and
      completed questionnaires and rapid testing for HIV, HCV, HBsAg, and syphilis;
      positive samples received confirmatory testing. Logistic regression was used to
      identify correlates of HIV, HCV, and current NSP use. RESULTS: Of 483
      participants, all were male and median age, age at first injection, and duration
      of injection were 28, 24, and 2.0 years, respectively. One-fifth (23.0%) had
      initiated injecting within the last year. Reported risky injecting practices
      included ever sharing needles/syringes (16.9%) or other injecting equipment
      (38.4%). Prevalence of HIV, HCV Ab, HBSAg, and syphilis was 2.1% (95% CI: 1.0
      3.8), 36.1% (95% CI: 31.8-40.4), 4.6% (95% CI: 2.9-6.9), and 1.2% (95% CI: 0.5
      2.7), respectively. HIV and HCV infection were both independently associated with
      sharing needles/syringes (AOR = 5.96, 95% CI: 1.58 - 22.38 and AOR = 2.33, 95%
      CI: 1.38 - 3.95, respectively). Approximately half (53.8%) of the participants
      were using NSP services at time of enrollment and 51.3% reported receiving
      syringes from NSPs in the last three months. Current NSP use was associated with
      initiating drug use with injecting (AOR = 2.58, 95% CI: 1.22 - 5.44), sharing
      injecting equipment in the last three months (AOR = 1.79, 95% CI: 1.16 - 2.77),
      prior incarceration (AOR = 1.57, 95% CI: 1.06 - 2.32), and greater daily
      frequency of injecting (AOR = 1.40 injections daily, 95% CI: 1.08 - 1.82).
      CONCLUSIONS: HIV and HCV prevalence appear stable among Kabul IDUs, though the
      substantial number having recently initiated injecting raises concern that
      transmission risk may increase over time. Harm reduction programming appears to
      be reaching high-risk drug user populations; however, monitoring is warranted to
      determine efficacy of prevention programming in this dynamic environment.

PMID- 21867519
TI  - Including non-additive genetic effects in Bayesian methods for the prediction of
      genetic values based on genome-wide markers.
AB  - BACKGROUND: Molecular marker information is a common source to draw inferences
      about the relationship between genetic and phenotypic variation. Genetic effects
      are often modelled as additively acting marker allele effects. The true mode of
      biological action can, of course, be different from this plain assumption. One
      possibility to better understand the genetic architecture of complex traits is to
      include intra-locus (dominance) and inter-locus (epistasis) interaction of
      alleles as well as the additive genetic effects when fitting a model to a trait.
      Several Bayesian MCMC approaches exist for the genome-wide estimation of genetic
      effects with high accuracy of genetic value prediction. Including pairwise
      interaction for thousands of loci would probably go beyond the scope of such a
      sampling algorithm because then millions of effects are to be estimated
      simultaneously leading to months of computation time. Alternative solving
      strategies are required when epistasis is studied. METHODS: We extended a fast
      Bayesian method (fBayesB), which was previously proposed for a purely additive
      model, to include non-additive effects. The fBayesB approach was used to estimate
      genetic effects on the basis of simulated datasets. Different scenarios were
      simulated to study the loss of accuracy of prediction, if epistatic effects were
      not simulated but modelled and vice versa. RESULTS: If 23 QTL were simulated to
      cause additive and dominance effects, both fBayesB and a conventional MCMC
      sampler BayesB yielded similar results in terms of accuracy of genetic value
      prediction and bias of variance component estimation based on a model including
      additive and dominance effects. Applying fBayesB to data with epistasis, accuracy
      could be improved by 5% when all pairwise interactions were modelled as well. The
      accuracy decreased more than 20% if genetic variation was spread over 230 QTL. In
      this scenario, accuracy based on modelling only additive and dominance effects
      was generally superior to that of the complex model including epistatic effects.
      CONCLUSIONS: This simulation study showed that the fBayesB approach is convenient
      for genetic value prediction. Jointly estimating additive and non-additive
      effects (especially dominance) has reasonable impact on the accuracy of
      prediction and the proportion of genetic variation assigned to the additive
      genetic source.

PMID- 21867521
TI  - Branch retinal vein occlusion associated with quetiapine fumarate.
AB  - BACKGROUND: To report a case of branch retinal vein occlusion in a young adult
      with bipolar mood disorder treated with quetiapine fumarate. CASE PRESENTATION: A
      29 years old gentleman who was taking quetiapine fumarate for 3 years for bipolar
      mood disorder, presented with sudden vision loss. He was found to have a superior
      temporal branch retinal vein occlusion associated with hypercholesterolemia.
      CONCLUSION: Atypical antipsychotic drugs have metabolic side effects which
      require regular monitoring and prompt treatment.

PMID- 21867520
TI  - Steady-state global optimization of metabolic non-linear dynamic models through
      recasting into power-law canonical models.
AB  - BACKGROUND: Design of newly engineered microbial strains for biotechnological
      purposes would greatly benefit from the development of realistic mathematical
      models for the processes to be optimized. Such models can then be analyzed and,
      with the development and application of appropriate optimization techniques, one
      could identify the modifications that need to be made to the organism in order to
      achieve the desired biotechnological goal. As appropriate models to perform such
      an analysis are necessarily non-linear and typically non-convex, finding their
      global optimum is a challenging task. Canonical modeling techniques, such as
      Generalized Mass Action (GMA) models based on the power-law formalism, offer a
      possible solution to this problem because they have a mathematical structure that
      enables the development of specific algorithms for global optimization. RESULTS:
      Based on the GMA canonical representation, we have developed in previous works a
      highly efficient optimization algorithm and a set of related strategies for
      understanding the evolution of adaptive responses in cellular metabolism. Here,
      we explore the possibility of recasting kinetic non-linear models into an
      equivalent GMA model, so that global optimization on the recast GMA model can be
      performed. With this technique, optimization is greatly facilitated and the
      results are transposable to the original non-linear problem. This procedure is
      straightforward for a particular class of non-linear models known as Saturable
      and Cooperative (SC) models that extend the power-law formalism to deal with
      saturation and cooperativity. CONCLUSIONS: Our results show that recasting non
      linear kinetic models into GMA models is indeed an appropriate strategy that
      helps overcoming some of the numerical difficulties that arise during the global
      optimization task.

PMID- 21867522
TI  - Comparison between two race/skin color classifications in relation to health
      related outcomes in Brazil.
AB  - BACKGROUND: This paper aims to compare the classification of race/skin color
      based on the discrete categories used by the Demographic Census of the Brazilian
      Institute of Geography and Statistics (IBGE) and a skin color scale with values
      ranging from 1 (lighter skin) to 10 (darker skin), examining whether choosing one
      alternative or the other can influence measures of self-evaluation of health
      status, health care service utilization and discrimination in the health
      services. METHODS: This is a cross-sectional study based on data from the World
      Health Survey carried out in Brazil in 2003 with a sample of 5000 individuals
      older than 18 years. Similarities between the two classifications were evaluated
      by means of correspondence analysis. The effect of the two classifications on
      health outcomes was tested through logistic regression models for each sex, using
      age, educational level and ownership of consumer goods as covariables. RESULTS:
      Both measures of race/skin color represent the same race/skin color construct.
      The results show a tendency among Brazilians to classify their skin color in
      shades closer to the center of the color gradient. Women tend to classify their
      race/skin color as a little lighter than men in the skin color scale, an effect
      not observed when IBGE categories are used. With regard to health and health care
      utilization, race/skin color was not relevant in explaining any of them,
      regardless of the race/skin color classification. Lack of money and social class
      were the most prevalent reasons for discrimination in healthcare reported in the
      survey, suggesting that in Brazil the discussion about discrimination in the
      health care must not be restricted to racial discrimination and should also
      consider class-based discrimination. The study shows that the differences of the
      two classifications of race/skin color are small. However, the interval scale
      measure appeared to increase the freedom of choice of the respondent.

PMID- 21867523
TI  - Mesothelioma of tunica vaginalis of "uncertain malignant potential" - an evolving
      concept: case report and review of the literature.
AB  - Mesothelioma of tunica vaginalis is a rare neoplasm, typically demonstrating
      frankly malignant morphology and aggressive behavior. Rare cases of well
      differentiated papillary mesotheliomas have also been reported, which, in
      contrast, demonstrate indolent behavior. There are, however, cases which do not
      fit into the well-differentiated or diffuse malignant mesothelioma categories and
      can be considered mesothelioma of tunica vaginalis of "uncertain malignant
      potential", which is an emerging diagnostic category. A 57-year-old man presented
      with a neoplasm in a hydrocele sac. The neoplasm was non-invasive, but showed
      focal complex and solid growth and it was difficult to categorize either as well
      differentiated papillary mesotheliomas or malignant mesothelioma. After the
      initial limited resection, the patient underwent radical orchiectomy with
      hemiscrotectomy and is alive and without disease progression after 6 years.
      Documentation of these rare tumors will allow their distinction from true
      malignant mesotheliomas and will facilitate the development of specific treatment
      recommendations.

PMID- 21867525
TI  - Biofunctionalization of zinc oxide nanowires for DNA sensory applications.
AB  - We report on the biofunctionalization of zinc oxide nanowires for the attachment
      of DNA target molecules on the nanowire surface. With the organosilane
      glycidyloxypropyltrimethoxysilane acting as a bifunctional linker, amino-modified
      capture molecule oligonucleotides have been immobilized on the nanowire surface.
      The dye-marked DNA molecules were detected via fluorescence microscopy, and our
      results reveal a successful attachment of DNA capture molecules onto the nanowire
      surface. The electrical field effect induced by the negatively charged attached
      DNA molecules should be able to control the electrical properties of the
      nanowires and gives way to a ZnO nanowire-based biosensing device.

PMID- 21867524
TI  - Transcriptomes of Frankia sp. strain CcI3 in growth transitions.
AB  - BACKGROUND: Frankia sp. strains are actinobacteria that form N2-fixing root
      nodules on angiosperms. Several reference genome sequences are available enabling
      transcriptome studies in Frankia sp. Genomes from Frankia sp. strains differ
      markedly in size, a consequence proposed to be associated with a high number of
      indigenous transposases, more than 200 of which are found in Frankia sp. strain
      CcI3 used in this study. Because Frankia exhibits a high degree of cell
      heterogeneity as a consequence of its mycelial growth pattern, its transcriptome
      is likely to be quite sensitive to culture age. This study focuses on the
      behavior of the Frankia sp. strain CcI3 transcriptome as a function of nitrogen
      source and culture age. RESULTS: To study global transcription in Frankia sp.
      CcI3 grown under different conditions, complete transcriptomes were determined
      using high throughput RNA deep sequencing. Samples varied by time (five days vs.
      three days) and by culture conditions (NH4+ added vs. N2 fixing). Assembly of
      millions of reads revealed more diversity of gene expression between five-day and
      three-day old cultures than between three day old cultures differing in nitrogen
      sources. Heat map analysis organized genes into groups that were expressed or
      repressed under the various conditions compared to median expression values.
      Twenty-one SNPs common to all three transcriptome samples were detected
      indicating culture heterogeneity in this slow-growing organism. Significantly
      higher expression of transposase ORFs was found in the five-day and N2-fixing
      cultures, suggesting that N starvation and culture aging provide conditions for
      on-going genome modification. Transposases have previously been proposed to
      participate in the creating the large number of gene duplication or deletion in
      host strains. Subsequent RT-qPCR experiments confirmed predicted elevated
      transposase expression levels indicated by the mRNA-seq data. CONCLUSIONS: The
      overall pattern of gene expression in aging cultures of CcI3 suggests significant
      cell heterogeneity even during normal growth on ammonia. The detection of
      abundant transcription of nif (nitrogen fixation) genes likely reflects the
      presence of anaerobic, N-depleted microsites in the growing mycelium of the
      culture, and the presence of significantly elevated transposase transcription
      during starvation indicates the continuing evolution of the Frankia sp. strain
      CcI3 genome, even in culture, especially under stressed conditions. These studies
      also sound a cautionary note when comparing the transcriptomes of Frankia grown
      in root nodules, where cell heterogeneity would be expected to be quite high.

PMID- 21867526
TI  - Detection of Hepatitis B virus subgenotype A1 in a Quilombo community from
      Maranhao, Brazil.
AB  - BACKGROUND: The Brazilian population is mainly descendant from European
      colonizers, Africans and Native Americans. Some Afro-descendants lived in small
      isolated communities since the slavery period. The epidemiological status of HBV
      infection in Quilombos communities from northeast of Brazil remains unknown. The
      aim of this study was to characterize the HBV genotypes circulating inside a
      Quilombo isolated community from Maranhao State, Brazil. METHODS: Seventy-two
      samples from Frechal Quilombo community at Maranhao were collected. All serum
      samples were screened by enzyme-linked immunosorbent assays for the presence of
      hepatitis B surface antigen (HBsAg). HBsAg positive samples were submitted to DNA
      extraction and a fragment of 1306 bp partially comprising HBsAg and polymerase
      coding regions (S/POL) was amplified by nested PCR and its nucleotide sequence
      was determined. Viral isolates were genotyped by phylogenetic analysis using
      reference sequences from each genotype obtained from GenBank (n = 320). Sequences
      were aligned using Muscle software and edited in the SE-AL software. Bayesian
      phylogenetic analyses were conducted using Markov Chain Monte Carlo (MCMC) method
      to obtain the MCC tree using BEAST v.1.5.3. RESULTS: Of the 72 individuals, 9
      (12.5%) were HBsAg-positive and 4 of them were successfully sequenced for the
      1306 bp fragment. All these samples were genotype A1 and grouped together with
      other sequences reported from Brazil. CONCLUSIONS: The present study represents
      the first report on the HBV genotypes characterization of this community in the
      Maranhao state in Brazil where a high HBsAg frequency was found. In this study,
      we reported a high frequency of HBV infection and the exclusive presence of
      subgenotype A1 in an Afro-descendent community in the Maranhao State, Brazil.

PMID- 21867527
TI  - Association between RUNX3 promoter methylation and gastric cancer: a meta
      analysis.
AB  - BACKGROUND: Runt-related transcription factor 3 (RUNX3) is a member of the runt
      domain family of transcription factors and has been reported to be a candidate
      tumor suppressor in gastric cancer. However, the association between RUNX3
      promoter methylation and gastric cancer remains unclear. METHODS: We
      systematically reviewed studies of RUNX3 promoter methylation and gastric cancer
      published in English or Chinese from January 2000 to January 2011, and quantified
      the association between RUNX3 promoter methylation and gastric cancer using meta
      analysis methods. RESULTS: A total of 1740 samples in 974 participants from
      seventeen studies were included in the meta-analysis. A significant association
      was observed between RUNX3 promoter methylation and gastric cancer, with an
      aggregated odds ratio (OR) of 5.63 (95%CI 3.15, 10.07). There was obvious
      heterogeneity among studies. Subgroup analyses (including by tissue origin,
      country and age), meta-regression were performed to determine the source of the
      heterogeneity. Meta-regression showed that the trend in ORs was inversely
      correlated with age. No publication bias was detected. The ORs for RUNX3
      methylation in well-differentiated vs undifferentiated gastric cancers, and in
      intestinal-type vs diffuse-type carcinomas were 0.59 (95%CI: 0.30, 1.16) and 2.62
      (95%CI: 1.33, 5.14), respectively. There were no significant differences in RUNX3
      methylation in cancer tissues in relation to age, gender, TNM stage, invasion of
      tumors into blood vessel or lymphatic ducts, or tumor stage. CONCLUSIONS: This
      meta-analysis identified a strong association between methylation of the RUNX3
      promoter and gastric cancer, confirming the role of RUNX3 as a tumor suppressor
      gene.

PMID- 21867528
TI  - Potential link between caffeine consumption and pediatric depression: A case
      control study.
AB  - BACKGROUND: Early-onset depressive disorders can have severe consequences both
      from developmental and functional aspects. The etiology of depressive disorders
      is complex and multi-factorial, with an intricate interaction among environmental
      factors and genetic predisposition. While data from studies on adults suggest
      that caffeine is fairly safe, effects of caffeine in children, who are in period
      of rapid brain development, are currently unknown. Furthermore, systematic
      research addressing the relationship between depressive symptoms in children and
      caffeine consumption is lacking.The present study examined the effects of
      caffeine consumption on depressed mood in children with depression and non
      depressed participants. METHODS: Children and adolescents (n = 51) already
      enrolled in an ongoing longitudinal study, aged 9-12 years, were assessed for
      depressive symptoms with the Children Depressive Inventory (CDI).
      Psychopathological symptoms were assessed with the Child Behavioral Checklist
      (CBCL) and eating habits were assessed with the Nutrition-Behavior Inventory
      (NBI) 1. The children were compared to control children without psychopathology
      attending public schools in a Southern Brazilian city. RESULTS: Participants with
      CDI scores >= 15 (mean = 19; S.D. = 4) also had high NBI scores (mean = 52; S.D.
      = 19, p < 0.001) suggestive of a relationship between depressive symptoms and
      environmental factors, in this case nutrition/behavior. Additional linear
      regression adjusted statistical analysis, considering the factors of consumption
      of sweets and caffeine individually, showed that caffeine, but not sweets, was
      associated with depressive symptoms. CONCLUSIONS: These findings indicate that
      depressed children consume more caffeinated drinks than non-depressed children.
      Nonetheless while a strong association between depressive symptoms and caffeine
      consumption among children was found, further research should investigate whether
      or not this association is due to a cause and effect relationship.

PMID- 21867529
TI  - Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF
      1 nuclear targeting defect.
AB  - BACKGROUND: Mutations of genes affecting surfactant homeostasis, such as SFTPB,
      SFTPC and ABCA3, lead to diffuse lung disease in neonates and children.
      Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor
      1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis
      and function--causes a rare form of progressive respiratory failure designated
      brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are
      heterogeneous and poorly explored. We report a novel TTF-1 molecular defect
      causing recurrent respiratory failure episodes in an infant. METHODS: The subject
      was an infant with severe neonatal respiratory distress syndrome followed by
      recurrent respiratory failure episodes, hypopituitarism and neurological
      abnormalities. Lung histology and ultrastructure were assessed by surgical
      biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing
      and array chromatine genomic hybridization (aCGH). Surfactant protein expression
      in lung tissue was analyzed by confocal immunofluorescence microscopy. For
      kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC)
      were isolated from serial tracheal aspirates after intravenous administration of
      stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was
      derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment
      curves. Six intubated infants with no primary lung disease were used as controls.
      RESULTS: Lung biopsy showed desquamative interstitial pneumonitis and lamellar
      body abnormalities suggestive of genetic surfactant deficiency. Genetic studies
      identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB,
      SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence
      studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of
      nucleus, indicating defective nuclear targeting. This pattern has not been
      reported in human and was not found in two healthy controls and in five ABCA3
      mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B
      synthesis (43.2 vs. 76.5 +/- 24.8%/day); conversely, DSPC synthesis was higher
      (12.4 vs. 6.3 +/- 0.5%/day) compared to controls, although there was a marked
      reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 +/- 12.4% of total
      phospholipid content). CONCLUSION: Defective TTF-1 signaling may result in
      profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung
      disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in
      other genetic surfactant defects.

PMID- 21867530
TI  - Mechanism of the chromosome-induced polar body extrusion in mouse eggs.
AB  - BACKGROUND: An oocyte undergoes two rounds of asymmetric division to generate a
      haploid gamete and two small polar bodies designed for apoptosis. Chromosomes
      play important roles in specifying the asymmetric meiotic divisions in the
      oocytes but the underlying mechanism is poorly understood. RESULTS: Chromosomes
      independently induce spindle formation and cortical actomyosin assembly into
      special cap and ring structures in the cortex of the oocyte. The spindle and the
      cortical cap/ring interact to generate mechanical forces, leading to polar body
      extrusion. Two distinct force-driven membrane changes were observed during 2nd
      polar body extrusion: a protrusion of the cortical cap and a membrane
      invagination induced by an anaphase spindle midzone. The cortical cap protrusion
      and invagination help rotate the spindle perpendicularly so that the spindle
      midzone can induce bilateral furrows at the shoulder of the protruding cap,
      leading to an abscission of the polar body. It is interesting to note that while
      the mitotic spindle midzone induces bilateral furrowing, leading to efficient
      symmetric division in the zygote, the meiotic spindle midzone induced cytokinetic
      furrowing only locally. CONCLUSIONS: Distinct forces driving cortical cap
      protrusion and membrane invagination are involved in spindle rotation and polar
      body extrusion during meiosis II in mouse oocytes.

PMID- 21867531
TI  - A questionnaire to measure melanoma risk, knowledge and protective behaviour:
      assessing content validity in a convenience sample of Scots and Australians.
AB  - BACKGROUND: The aim of this study was to assess the content validity of a
      questionnaire to measure melanoma risk, knowledge and protective behaviour in a
      convenience sample of Scots and Australians. Australia has the highest melanoma
      incidence worldwide but has developed a culture of skin cancer avoidance with a
      long history of skin cancer primary prevention campaigns of proven effectiveness.
      Scotland has lower incidence, but has shown a greater rate of increase between
      1985 and 2007. There is an urgent need in Scotland, therefore, to identify those
      groups at greatest risk and provide them with effective preventative advice.
      METHOD: A self-administered postal survey was completed by four groups formed
      from convenience samples in two geographical locations (Northeast Scotland and
      Western Australia). In univariate analysis scores on personal risk, level of
      concern, protective behaviour, and knowledge were compared by nationality,
      previous skin cancer diagnosis and personally knowing someone with melanoma.
      Multivariate linear regression analysis modelled the influence of potential
      predictor variables upon each of the scores. RESULTS: 540 people completed the
      questionnaire, 273 Scots (50.6%). 133 (24.6%) Scots and 83 (15.4%) Australians
      previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2%) Scots and
      190 (35.2%) Australians personally knew someone with melanoma. Australians had
      higher knowledge (p < 0.001), level of concern (p < 0.001) and protective
      behaviour (p < 0.001) scores than the Scottish. Australian nationality was the
      strongest independent predictor of a higher knowledge score (p < 0.001), followed
      by a previous skin cancer diagnosis (p = 0.003), personal knowledge of someone
      with melanoma (p = 0.011), female gender (p = 0.005) and higher education status
      (p < 0.001) (R(2) = 0.163). CONCLUSION: The questionnaire detected higher levels
      of knowledge and skin cancer protective behaviours in Australians than in
      Scottish people. This was expected and supports the content validity of the
      questionnaire and its value as a future research tool in the Scottish population.

PMID- 21867532
TI  - Neuromuscular electrical stimulation and biofeedback therapy may improve
      endometrial growth for patients with thin endometrium during frozen-thawed embryo
      transfer: a preliminary report.
AB  - BACKGROUND: To investigate the effect of pelvic floor Neuromuscular Electrical
      Stimulation (NMES) Therapy in improving endometrial thickness in women with thin
      endometrium. METHODS: 41 patients undergoing assisted reproduction with a thin
      endometrium (less than or equal to7 mm) were recruited and advised to go for a
      pelvic floor NMES in frozen-thawed embryo transfer cycle. PHENIX Neuromuscular
      Electrical Stimulation Therapy System was used according to the manufacturer's
      recommended protocol for 20 to 30 minutes of intermittent vaginal electrical
      stimulation on the treatment days. RESULTS: A total of 20 and 21 were included in
      the NMES and non-NMES groups respectively. 12 out of 20 (60%) patients developed
      endometrial thickness equal to or more than 8 mm after the NMES therapy, which
      was the primary outcome. The mean thickness of endometrium before and after was
      respectively 5.60 mm (0.82 mm) and 7.93 mm (1.42 mm) in the therapy group versus
      5.50 mm (1.00) and 6.78 mm (0.47) in the control group; the difference was
      statistically significant (P = 0.002). There was higher pregnancy rate in the
      NMES group (42% versus 35%) but the difference was not statistically significant.
      CONCLUSION: Neuromuscular Electrical stimulation therapy may be effective for the
      patients with a thin endometrium. Further studies are needed to investigate its
      effectiveness.

PMID- 21867533
TI  - Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter
      study from Thailand.
AB  - BACKGROUND: Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common
      worldwide, but it is the most common T- and NK-cell lymphomas in many Asian
      countries. Immunophenotypic profiles were studied based on limited series. The
      authors, therefore, studied on ENKTL according to characterize immunophenotypic
      profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.
      METHODS: By using tissue microarray (TMA), immunohistochemical study and EBV
      encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR)
      gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the
      available cases. RESULTS: There were 22 cases eligible for TMA. ENKTL were
      positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%),
      granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and
      IRF4/MUM1 (33%). None of them was positive for betaF1, CD8, or CD57. TCR gene
      rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15
      tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression
      demonstrated a significantly poorer survival outcome (p = 0.008). CONCLUSIONS:
      The present study demonstrated TIA-1 and EBER as the two most sensitive markers.
      There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of
      CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a
      subset of cases. Based on the present study in conjunction with the literature
      review, determination of PCR-based TCR gene rearrangement analysis might not be a
      useful technique for making diagnosis of ENKTL.

PMID- 21867535
TI  - Experimental annotation of post-translational features and translated coding
      regions in the pathogen Salmonella Typhimurium.
AB  - BACKGROUND: Complete and accurate genome annotation is crucial for comprehensive
      and systematic studies of biological systems. However, determining protein-coding
      genes for most new genomes is almost completely performed by inference using
      computational predictions with significant documented error rates (> 15%).
      Furthermore, gene prediction programs provide no information on biologically
      important post-translational processing events critical for protein function.
      RESULTS: We experimentally annotated the bacterial pathogen Salmonella
      Typhimurium 14028, using "shotgun" proteomics to accurately uncover the
      translational landscape and post-translational features. The data provide protein
      level experimental validation for approximately half of the predicted protein
      coding genes in Salmonella and suggest revisions to several genes that appear to
      have incorrectly assigned translational start sites, including a potential novel
      alternate start codon. Additionally, we uncovered 12 non-annotated genes missed
      by gene prediction programs, as well as evidence suggesting a role for one of
      these novel ORFs in Salmonella pathogenesis. We also characterized post
      translational features in the Salmonella genome, including chemical modifications
      and proteolytic cleavages. We find that bacteria have a much larger and more
      complex repertoire of chemical modifications than previously thought including
      several novel modifications. Our in vivo proteolysis data identified more than
      130 signal peptide and N-terminal methionine cleavage events critical for protein
      function. CONCLUSION: This work highlights several ways in which application of
      proteomics data can improve the quality of genome annotations to facilitate novel
      biological insights and provides a comprehensive proteome map of Salmonella as a
      resource for systems analysis.

PMID- 21867536
TI  - A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced
      mammary tumorigenesis.
AB  - BACKGROUND: Epidemiological evidence suggests that moderately elevated levels of
      circulating insulin-like growth factor-I (IGF-I) are associated with increased
      risk of breast cancer in women. How circulating IGF-I may promote breast cancer
      incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab
      resistance in ErbB2 positive breast cancer. Few models have directly examined the
      effect of moderately high levels of circulating IGF-I on breast cancer initiation
      and progression. The purpose of this study was to assess the ability of
      circulating IGF-I to independently initiate mammary tumorigenesis and/or
      accelerate the progression of ErbB2 mediated mammary tumor growth. METHODS: We
      crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate
      4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2
      only, and wild type (wt). Virgin females were palpated twice a week and harvested
      when tumors reached 1000 mm(3). For study of normal development, blood and tissue
      were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. RESULTS: TTR
      IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in
      circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of
      circulating IGF-I had no effect upon pubertal mammary gland development. The
      transgenic increase in IGF-I alone wasn't sufficient to initiate mammary
      tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced
      mammary tumorigenesis or metastasis, with median time to tumor formation being 30
      wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65).
      Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was
      elevated in a similar manner to the circulating IGF-I, however, there was no
      effect on the rate of tumor growth (p = 0.23). There were no morphological
      differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2
      mammary glands. CONCLUSION: Using the first transgenic animal model to elevate
      circulating levels of IGF-I to those comparable to women at increased risk of
      breast cancer, we showed that moderately high levels of systemic IGF-I have no
      effect on pubertal mammary gland development, initiating mammary tumorigenesis or
      promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2
      induced mammary tumorigenesis is independent of the normal variation in
      circulating levels of IGF-I.

PMID- 21867537
TI  - DNA methylation of SPARC and chronic low back pain.
AB  - BACKGROUND: The extracellular matrix protein SPARC (Secreted Protein, Acidic,
      Rich in Cysteine) has been linked to degeneration of the intervertebral discs and
      chronic low back pain (LBP). In humans, SPARC protein expression is decreased as
      a function of age and disc degeneration. In mice, inactivation of the SPARC gene
      results in the development of accelerated age-dependent disc degeneration
      concurrent with age-dependent behavioral signs of chronic LBP.DNA methylation is
      the covalent modification of DNA by addition of methyl moieties to cytosines in
      DNA. DNA methylation plays an important role in programming of gene expression,
      including in the dynamic regulation of changes in gene expression in response to
      aging and environmental signals. We tested the hypothesis that DNA methylation
      down-regulates SPARC expression in chronic LBP in pre-clinical models and in
      patients with chronic LBP. RESULTS: Our data shows that aging mice develop
      anatomical and behavioral signs of disc degeneration and back pain, decreased
      SPARC expression and increased methylation of the SPARC promoter. In parallel, we
      show that human subjects with back pain exhibit signs of disc degeneration and
      increased methylation of the SPARC promoter. Methylation of either the human or
      mouse SPARC promoter silences its activity in transient transfection assays.
      CONCLUSIONS: This study provides the first evidence that DNA methylation of a
      single gene plays a role in chronic pain in humans and animal models. This has
      important implications for understanding the mechanisms involved in chronic pain
      and for pain therapy.

PMID- 21867534
TI  - Treatment of allergic asthma: modulation of Th2 cells and their responses.
AB  - Atopic asthma is a chronic inflammatory pulmonary disease characterised by
      recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell
      mediated inflammatory response in the airways. It is currently treated and, more
      or less, controlled depending on severity, with bronchodilators e.g. long-acting
      beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs
      such as corticosteroids (inhaled or oral), leukotriene modifiers, theophyline and
      anti-IgE therapy. Unfortunately, none of these treatments are curative and some
      asthmatic patients do not respond to intense anti-inflammatory therapies.
      Additionally, the use of long-term oral steroids has many undesired side effects.
      For this reason, novel and more effective drugs are needed. In this review, we
      focus on the CD4+ Th2 cells and their products as targets for the development of
      new drugs to add to the current armamentarium as adjuncts or as potential stand
      alone treatments for allergic asthma. We argue that in early disease, the
      reduction or elimination of allergen-specific Th2 cells will reduce the
      consequences of repeated allergic inflammatory responses such as lung remodelling
      without causing generalised immunosuppression.

PMID- 21867538
TI  - Vascular endothelial growth factor regulates melanoma cell adhesion and growth in
      the bone marrow microenvironment via tumor cyclooxygenase-2.
AB  - BACKGROUND: Human melanoma frequently colonizes bone marrow (BM) since its
      earliest stage of systemic dissemination, prior to clinical metastasis
      occurrence. However, how melanoma cell adhesion and proliferation mechanisms are
      regulated within bone marrow stromal cell (BMSC) microenvironment remain unclear.
      Consistent with the prometastatic role of inflammatory and angiogenic factors,
      several studies have reported elevated levels of cyclooxygenase-2 (COX-2) in
      melanoma although its pathogenic role in bone marrow melanoma metastasis is
      unknown. METHODS: Herein we analyzed the effect of cyclooxygenase-2 (COX-2)
      inhibitor celecoxib in a model of generalized BM dissemination of left cardiac
      ventricle-injected B16 melanoma (B16M) cells into healthy and bacterial endotoxin
      lipopolysaccharide (LPS)-pretreated mice to induce inflammation. In addition,
      B16M and human A375 melanoma (A375M) cells were exposed to conditioned media from
      basal and LPS-treated primary cultured murine and human BMSCs, and the
      contribution of COX-2 to the adhesion and proliferation of melanoma cells was
      also studied. RESULTS: Mice given one single intravenous injection of LPS 6 hour
      prior to cancer cells significantly increased B16M metastasis in BM compared to
      untreated mice; however, administration of oral celecoxib reduced BM metastasis
      incidence and volume in healthy mice, and almost completely abrogated LPS
      dependent melanoma metastases. In vitro, untreated and LPS-treated murine and
      human BMSC-conditioned medium (CM) increased VCAM-1-dependent BMSC adherence and
      proliferation of B16M and A375M cells, respectively, as compared to basal medium
      treated melanoma cells. Addition of celecoxib to both B16M and A375M cells
      abolished adhesion and proliferation increments induced by BMSC-CM. TNFalpha and
      VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti
      VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated
      BMSC-CM resulted in a complete abrogation of both adhesion- and proliferation
      stimulating effect of BMSC on melanoma cells. Conversely, recombinant VEGF
      increased adherence to BMSC and proliferation of both B16M and A375M cells,
      compared to basal medium-treated cells, while addition of celecoxib neutralized
      VEGF effects on melanoma. Recombinant TNFalpha induced B16M production of VEGF
      via COX-2-dependent mechanism. Moreover, exogenous PGE2 also increased B16M cell
      adhesion to immobilized recombinant VCAM-1. CONCLUSIONS: We demonstrate the
      contribution of VEGF-induced tumor COX-2 to the regulation of adhesion- and
      proliferation-stimulating effects of TNFalpha, from endotoxin-activated bone
      marrow stromal cells, on VLA-4-expressing melanoma cells. These data suggest COX
      2 neutralization as a potential anti-metastatic therapy in melanoma patients at
      high risk of systemic and bone dissemination due to intercurrent infectious and
      inflammatory diseases.

PMID- 21867540
TI  - Between-centre differences and treatment effects in randomized controlled trials:
      a case study in traumatic brain injury.
AB  - BACKGROUND: In Traumatic Brain Injury (TBI), large between-centre differences in
      outcome exist and many clinicians believe that such differences influence
      estimation of the treatment effect in randomized controlled trial (RCTs). The aim
      of this study was to assess the influence of between-centre differences in
      outcome on the estimated treatment effect in a large RCT in TBI. METHODS: We used
      data from the MRC CRASH trial on the efficacy of corticosteroid infusion in
      patients with TBI. We analyzed the effect of the treatment on 14 day mortality
      with fixed effect logistic regression. Next we used random effects logistic
      regression with a random intercept to estimate the treatment effect taking into
      account between-centre differences in outcome. Between-centre differences in
      outcome were expressed with a 95% range of odds ratios (OR) for centres compared
      to the average, based on the variance of the random effects (tau2). A random
      effects logistic regression model with random slopes was used to allow the
      treatment effect to vary by centre. The variation in treatment effect between the
      centres was expressed in a 95% range of the estimated treatment ORs. RESULTS: In
      9978 patients from 237 centres, 14-day mortality was 19.5%. Mortality was higher
      in the treatment group (OR = 1.22, p = 0.00010). Using a random effects model
      showed large between-centre differences in outcome (95% range of centre effects:
      0.27- 3.71), but did not substantially change the estimated treatment effect (OR
      = 1.24, p = 0.00003). There was limited, although statistically significant,
      between-centre variation in the treatment effect (OR = 1.22, 95% treatment OR
      range: 1.17-1.26). CONCLUSION: Large between-centre differences in outcome do not
      necessarily affect the estimated treatment effect in RCTs, in contrast to current
      beliefs in the clinical area of TBI.

PMID- 21867539
TI  - Reducing depression in older home care clients: design of a prospective study of
      a nurse-led interprofessional mental health promotion intervention.
AB  - BACKGROUND: Very little research has been conducted in the area of depression
      among older home care clients using personal support services. These older adults
      are particularly vulnerable to depression because of decreased cognition,
      comorbid chronic conditions, functional limitations, lack of social support, and
      reduced access to health services. To date, research has focused on
      collaborative, nurse-led depression care programs among older adults in primary
      care settings. Optimal management of depression among older home care clients is
      not currently known. The objective of this study is to evaluate the feasibility,
      acceptability and effectiveness of a 6-month nurse-led, interprofessional mental
      health promotion intervention aimed at older home care clients with depressive
      symptoms using personal support services. METHODS/DESIGN: This one-group pre-test
      post-test study aims to recruit a total of 250 long-stay (> 60 days) home care
      clients, 70 years or older, with depressive symptoms who are receiving personal
      support services through a home care program in Ontario, Canada. The nurse-led
      intervention is a multi-faceted 6-month program led by a Registered Nurse that
      involves regular home visits, monthly case conferences, and evidence-based
      assessment and management of depression using an interprofessional approach. The
      primary outcome is the change in severity of depressive symptoms from baseline to
      6 months using the Centre for Epidemiological Studies in Depression Scale.
      Secondary outcomes include changes in the prevalence of depressive symptoms and
      anxiety, health-related quality of life, cognitive function, and the rate and
      appropriateness of depression treatment from baseline to 12 months. Changes in
      the costs of use of health services will be assessed from a societal perspective.
      Descriptive and qualitative data will be collected to examine the feasibility and
      acceptability of the intervention and identify barriers and facilitators to
      implementation. DISCUSSION: Data collection began in May 2010 and is expected to
      be completed by July 2012. A collaborative nurse-led strategy may provide a
      feasible, acceptable and effective means for improving the health of older home
      care clients by improving the prevention, recognition, and management of
      depression in this vulnerable population. The challenges involved in designing a
      practical, transferable and sustainable nurse-led intervention in home care are
      also discussed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407926.

PMID- 21867541
TI  - Evaluation of the global association between cholesterol-associated polymorphisms
      and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in
      disease risk.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have identified single
      nucleotide polymorphisms (SNP)s that are essentially unequivocally associated
      with peripheral cholesterol. Since the alleles of the APOE gene, which modulate
      peripheral cholesterol metabolism, and midlife plasma cholesterol are both
      associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis
      that SNPs associated with plasma cholesterol are also associated with AD.
      RESULTS: Seventeen non-APOE SNPs reproducibly associated with cholesterol per
      GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects.
      As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662
      and rs1532085, are associated with AD risk and age-of-onset. Additionally,
      rs3846662 was associated with HMGCR exon 13 splicing in human liver but not
      brain, possibly obscured by CNS cell-type heterogeneity. However, rs3846662 was
      associated with HMGCR exon 13 splicing in liver- and brain-derived cell lines.
      CONCLUSIONS: Cholesterol-associated SNPs outside of APOE confer a global risk for
      AD. Rs3846662 and rs1532085 are associated with both AD risk and age-of-onset.
      Rs3846662 is associated with HMGCR exon 13 inclusion. Since rs3846662 affects AD
      risk and age-of-onset as well as statin responsiveness, this SNP may confound
      clinical trials evaluating the protective effects of statins on AD.

PMID- 21867542
TI  - Control of prostate cancer associated with withdrawal of a supplement containing
      folic acid, L-methyltetrahydrofolate and vitamin B12: a case report.
AB  - INTRODUCTION: This is the first report of possible direct stimulation of hormone
      resistant prostate cancer or interference of docetaxel cytotoxicity of prostate
      cancer in a patient with biochemical relapse of prostatic-specific antigen. This
      observation is of clinical and metabolic importance, especially at a time when
      more than 80 countries have fortified food supplies with folic acid and some
      contemplate further fortification with vitamin B12. CASE PRESENTATION: Our
      patient is a 71-year-old Caucasian man who had been diagnosed in 1997 with
      prostate cancer, stage T1c, and Gleason score 3+4 = 7. His primary treatment
      included intermittent androgen deprivation therapy including leuprolide +
      bicalutamide + deutasteride, ketoconazole + hydrocortisone, nilandrone and
      flutamide to resistance defined as biochemical relapse of PSA. While undergoing
      docetaxel therapy to treat a continually increasing prostate-specific antigen
      level, withdrawal of 10 daily doses of a supplement containing 500 MUg of vitamin
      B12 as cyanocobalamin, as well as 400 MUg of folic acid as pteroylglutamic acid
      and 400 MUg of L-5-methyltetrahydrofolate for a combined total of 800 MUg of
      mixed folates, was associated with a return to a normal serum prostatic-specific
      antigen level. CONCLUSION: This case report illustrates the importance of the
      effects of supplements containing large amounts of folic acid, L-5
      methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer
      cells directly and/or B vitamin interference with docetaxel efficacy. Physicians
      caring for patients with prostate cancer undergoing watchful waiting, hormone
      therapy, and/or chemotherapy should consider the possible acceleration of tumor
      growth and/or metastasis and the development of drug resistance associated with
      supplement ingestion. We describe several pathways of metabolic and epigenetic
      interactions that could affect the observed changes in serum levels of prostate
      specific antigen.

PMID- 21867543
TI  - Functional characterization of the complement receptor type 1 and its circulating
      ligands in patients with schizophrenia.
AB  - BACKGROUND: Whereas the complement system alterations contribute to
      schizophrenia, complement receptors and regulators are little studied. We
      investigated complement receptor type 1 (CR1) expression on blood cells, the
      levels of circulating immune complexes (CIC) containing ligands of CR1, C1q
      complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and
      CR1 C5507G functional polymorphism in schizophrenia patients and controls.
      RESULTS: We found an increased C1q-CIC level and CR1 expression on blood cells,
      elevated number of CR1 positive erythrocytes and reduced number of CR1 positive
      lymphocytes and monocytes in patients compared to controls. No difference in the
      levels of C3d-CIC between groups was observed. Higher CR1 expression on
      erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no
      difference was observed for other cell populations. Our results indicated that
      schizophrenia is associated with the increased CR1 expression and C1q-CIC level.
      CONCLUSIONS: Our study for the first time indicated that schizophrenia is
      associated with the increased CR1 expression and C1q-CIC level. Further studies
      in other ethnic groups are needed to replicate these findings.

PMID- 21867544
TI  - The association between socio-demographic characteristics and adherence to breast
      and colorectal cancer screening: analysis of large sub populations.
AB  - BACKGROUND: Populations having lower socioeconomic status, as well as ethnic
      minorities, have demonstrated lower utilization of preventive screening,
      including tests for early detection of breast and colorectal cancer. THE
      OBJECTIVE: To explore socio-demographic disparities in adherence to screening
      recommendations for early detection of cancer. METHODS: The study was conducted
      by Maccabi Healthcare Services, an Israeli HMO (health plan) providing healthcare
      services to 1.9 million members. Utilization of breast cancer (BC) and colorectal
      cancer (CC) screening were analyzed by socio-economic ranks (SERs), ethnicity
      (Arab vs non-Arab), immigration status and ownership of voluntarily supplemental
      health insurance (VSHI). RESULTS: Data on 157,928 and 303,330 adults, eligible
      for BC and CC screening, respectively, were analyzed. Those having lower SER,
      Arabs, immigrants from Former Soviet Union countries and non-owners of VSHI
      performed fewer cancer screening examinations compared with those having higher
      SER, non-Arabs, veterans and owners of VSHI (p < 0.001). Logistic regression
      model for BC Screening revealed a positive association with age and ownership of
      VSHI and a negative association with being an Arab and having a lower SER. The
      model for CC screening revealed a positive association with age and ownership of
      VSHI and a negative association with being an Arab, having a lower SER and being
      an immigrant. The model estimated for BC and CC screening among females revealed
      a positive association with age and ownership of VSHI and a negative association
      with being an Arab, having a lower SER and being an immigrant. CONCLUSION:
      Patients from low socio-economic backgrounds, Arabs, immigrants and those who do
      not own supplemental insurance do fewer tests for early detection of cancer.
      These sub-populations should be considered priority populations for targeted
      intervention programs and improved resource allocation.

PMID- 21867545
TI  - Acute pancreatitis with saw palmetto use: a case report.
AB  - INTRODUCTION: Saw palmetto is a phytotherapeutic agent commercially marketed for
      the treatment of benign prostatic hyperplasia. Evidence suggests that saw
      palmetto is a safe product, and mild gastrointestinal adverse effects have been
      reported with its use. We report a case of acute pancreatitis, possibly secondary
      to the use of saw palmetto. CASE PRESENTATION: A 61-year-old Caucasian man with a
      history of benign prostatic hyperplasia and gastroesophageal reflux disease
      developed epigastric pain associated with nausea 36 hours prior to presentation.
      He denied drinking alcohol prior to the development of his symptoms. His home
      medications included saw palmetto, lansoprazole and multivitamins. Laboratory
      results revealed elevated lipase and amylase levels. An abdominal ultrasound
      demonstrated a nondilated common bile duct, without choledocholithiasis. Computed
      tomography of his abdomen showed the pancreatic tail with peripancreatic
      inflammatory changes, consistent with acute pancreatitis. Our patient's condition
      improved with intravenous fluids and pain management. On the fourth day of
      hospitalization his pancreatic enzymes were within normal limits: he was
      discharged home and advised to avoid taking saw palmetto. CONCLUSION: It is our
      opinion that a relationship between saw palmetto and the onset of acute
      pancreatitis is plausible, and prescribers and users of saw palmetto should be
      alert to the possibility of such adverse reactions.

PMID- 21867546
TI  - Carotid angiodysplasia complicated by the use of anti-hypertensive drugs during
      pregnancy: a case report.
AB  - INTRODUCTION: Hypertensive syndromes in pregnancy are one of the leading causes
      of obstetric admissions into intensive care units. They are related to changes in
      the central nervous system caused by a decrease in cerebral perfusion pressure,
      indicated by an increase in intracranial pressure. These changes in pressure
      usually result from acute injuries or a decrease in the mean arterial pressure
      due to iatrogenic action or shock. However, other vascular disorders may
      contribute to similar occurrences. CASE PRESENTATION: A 15-year-old girl was
      admitted to our hospital complaining of severe headaches since the eighth month
      of pregnancy, and presented with an arterial blood pressure of 180/120 mmHg. The
      diagnostic hypothesis was pre-eclampsia. Our patient's blood pressure levels
      remained elevated, and she was submitted to a cesarean section. After the
      procedure, she was referred to our infirmary, presenting with a blank distant
      look and with no interaction with the environment, dyslalia, and labial and upper
      and lower right limb paresis. She was confused and unable to speak, but responded
      to painful stimuli as she conveyed abdominal pain at superficial and deep
      palpation. The hypothesis of post-partum psychosis was suggested. She was then
      transferred to our intensive care unit, maintaining an impassive attitude in bed
      but reacting to external stimuli. Results of a computed tomography scan revealed
      ischemic infarction of the territory of her left middle cerebral artery. A
      selective cerebral arteriography showed bilateral occlusion of her internal
      carotid artery in the intracranial position, prebifurcation and angiodysplasia in
      the cervical segments of her internal carotid artery. Sixteen days after hospital
      admission, our patient died. CONCLUSION: This data shows the need for careful
      monitoring of hypertensive syndromes in pregnancy cases, especially in cases with
      a history of chronic hypertension or with vascular alterations, It also
      highlights the need for constant supervision of blood pressure levels during the
      use of anti-hypertensive medications.

PMID- 21867547
TI  - Placenta previa percreta left in situ - management by delayed hysterectomy: a
      case report.
AB  - INTRODUCTION: Placenta percreta is an obstetric emergency often associated with
      massive hemorrhage and emergency hysterectomy. CASE PRESENTATION: We present the
      case of a 30-year-old African woman, gravida 7, para 5, with placenta percreta
      managed by an alternative approach: the placenta was left in situ, methotrexate
      was administered, and a delayed hysterectomy was successfully performed.
      CONCLUSIONS: Further studies are needed to develop the most appropriate
      management option for the most severe cases of abnormal placentation. Delayed
      hysterectomy may be a reasonable strategy in the most severe cases.

PMID- 21867548
TI  - Development of a method for environmentally friendly chemical peptide synthesis
      in water using water-dispersible amino acid nanoparticles.
AB  - Due to the vast importance of peptides in biological processes, there is an
      escalating need for synthetic peptides to be used in a wide variety of
      applications. However, the consumption of organic solvent is extremely large in
      chemical peptide syntheses because of the multiple condensation steps in organic
      solvents. That is, the current synthesis method is not environmentally friendly.
      From the viewpoint of green sustainable chemistry, we focused on developing an
      organic solvent-free synthetic method using water, an environmentally friendly
      solvent. Here we described in-water synthesis technology using water-dispersible
      protected amino acids.

PMID- 21867549
TI  - A rapid in situ procedure for determination of bacterial susceptibility or
      resistance to antibiotics that inhibit peptidoglycan biosynthesis.
AB  - BACKGROUND: Antibiotics which inhibit bacterial peptidoglycan biosynthesis are
      the most widely used in current clinical practice. Nevertheless, resistant
      strains increase dramatically, with serious economic impact and effects on public
      health, and are responsible for thousands of deaths each year. Critical clinical
      situations should benefit from a rapid procedure to evaluate the sensitivity or
      resistance to antibiotics that act at the cell wall. We have adapted a kit for
      rapid determination of bacterial DNA fragmentation, to assess cell wall
      integrity. RESULTS: Cells incubated with the antibiotic were embedded in an
      agarose microgel on a slide, incubated in an adapted lysis buffer, stained with a
      DNA fluorochrome, SYBR Gold and observed under fluorescence microscopy. The lysis
      affects the cells differentially, depending on the integrity of the wall. If the
      bacterium is susceptible to the antibiotic, the weakened cell wall is affected by
      the lysing solution so the nucleoid of DNA contained inside the bacterium is
      released and spread. Alternatively, if the bacterium is resistant to the
      antibiotic, it is practically unaffected by the lysis solution and does not
      liberate the nucleoid, retaining its normal morphological appearance. In an
      initial approach, the procedure accurately discriminates susceptible,
      intermediate and resistant strains of Escherichia coli to amoxicillin/clavulanic
      acid. When the bacteria came from an exponentially growing liquid culture, the
      effect on the cell wall of the beta-lactam was evident much earlier that when
      they came from an agar plate. A dose-response experiment with an E. coli strain
      susceptible to ampicillin demonstrated a weak effect before the MIC dose. The
      cell wall damage was not homogenous among the different cells, but the level of
      damage increased as dose increased with a predominant degree of effect for each
      dose. A microgranular-fibrilar extracellular background was evident in gram
      negative susceptible strains after beta-lactam treatment. This material was
      digested by DNase I, hybridised with a specific whole genome probe, and so
      recognized as DNA fragments released by the bacteria. Finally, 46 clinical
      strains from eight gram-negative and four gram-positive species were evaluated
      blind for susceptibility or resistance to one of four different beta-lactams and
      vancomycin, confirming the applicability of the methodology. CONCLUSION: The
      technique to assess cell wall integrity appears to be a rapid and simple
      procedure to identify resistant and susceptible strains to antibiotics that
      interfere with peptidoglycan biosynthesis.

PMID- 21867550
TI  - Development and evaluation of a prototype non-woven fabric filter for
      purification of malaria-infected blood.
AB  - BACKGROUND: Many malaria-related studies depend on infected red blood cells
      (iRBCs) as fundamental material; however, infected blood samples from human or
      animal models include leukocytes (white blood cells or WBCs), especially
      difficult to separate from iRBCs in cases involving Plasmodium vivax. These host
      WBCs are a source of contamination in biology, immunology and molecular biology
      studies, requiring their removal. Non-woven fabric (NWF) has the ability to
      adsorb leukocytes and is already used as filtration material to deplete WBCs for
      blood transfusion and surgery. The present study describes the development and
      evaluation of a prototype NWF filter designed for purifying iRBCs from malaria
      infected blood. METHODS: Blood samples of P. vivax patients were processed
      separately by NWF filter and CF11 column methods. WBCs and RBCs were counted,
      parasite density, morphology and developing stage was checked by microscopy, and
      compared before and after treatment. The viability of filtrated P. vivax
      parasites was examined by in vitro short-term cultivation. RESULTS: A total of 15
      P. vivax-infected blood samples were treated by both NWF filter and CF11 methods.
      The WBC removal rate of the NWF filter method was 99.03%, significantly higher
      than the CF11 methods (98.41%, P < 0.01). The RBC recovery rate of the NWF filter
      method was 95.48%, also significantly higher than the CF11 method (87.05%, P <
      0.01). Fourteen in vitro short-term culture results showed that after filter
      treatment, P. vivax parasite could develop as normal as CF11 method, and no
      obvious density, developing stage difference were fund between two methods.
      CONCLUSIONS: NWF filter filtration removed most leukocytes from malaria-infected
      blood, and the recovery rate of RBCs was higher than with CF11 column method.
      Filtrated P. vivax parasites were morphologically normal, viable, and suitable
      for short-term in vitro culture. NWF filter filtration is simple, fast and
      robust, and is ideal for purification of malaria-infected blood.

PMID- 21867551
TI  - Epigenetic regulation of caloric restriction in aging.
AB  - The molecular mechanisms of aging are the subject of much research and have
      facilitated potential interventions to delay aging and aging-related degenerative
      diseases in humans. The aging process is frequently affected by environmental
      factors, and caloric restriction is by far the most effective and established
      environmental manipulation for extending lifespan in various animal models.
      However, the precise mechanisms by which caloric restriction affects lifespan are
      still not clear. Epigenetic mechanisms have recently been recognized as major
      contributors to nutrition-related longevity and aging control. Two primary
      epigenetic codes, DNA methylation and histone modification, are believed to
      dynamically influence chromatin structure, resulting in expression changes of
      relevant genes. In this review, we assess the current advances in epigenetic
      regulation in response to caloric restriction and how this affects cellular
      senescence, aging and potential extension of a healthy lifespan in humans.
      Enhanced understanding of the important role of epigenetics in the control of the
      aging process through caloric restriction may lead to clinical advances in the
      prevention and therapy of human aging-associated diseases.

PMID- 21867552
TI  - Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium
      falciparum parasites.
AB  - BACKGROUND: Resistance to anti-malarial drugs is a widespread problem for control
      programmes for this devastating disease. Molecular tests are available for many
      anti-malarial drugs and are useful tools for the surveillance of drug resistance.
      However, the correlation of treatment outcome and molecular tests with particular
      parasite markers is not perfect, due in part to individuals who are able to clear
      genotypically drug-resistant parasites. This study aimed to identify molecular
      markers in the human genome that correlate with the clearance of malaria
      parasites after drug treatment, despite the drug resistance profile of the
      protozoan as predicted by molecular approaches. METHODS: 3721 samples from five
      African countries, which were known to contain genotypically drug resistant
      parasites, were analysed. These parasites were collected from patients who
      subsequently failed to clear their infection following drug treatment, as
      expected, but also from patients who successfully cleared their infections with
      drug-resistant parasites. 67 human polymorphisms (SNPs) on 17 chromosomes were
      analysed using Sequenom's mass spectrometry iPLEX gold platform, to identify
      regions of the human genome, which contribute to enhanced clearance of drug
      resistant parasites. RESULTS: An analysis of all data from the five countries
      revealed significant associations between the phenotype of ability to clear drug
      resistant Plasmodium falciparum infection and human immune response loci common
      to all populations. Overall, three SNPs showed a significant association with
      clearance of drug-resistant parasites with odds ratios of 0.76 for SNP rs2706384
      (95% CI 0.71-0.92, P = 0.005), 0.66 for SNP rs1805015 (95% CI 0.45-0.97, P =
      0.03), and 0.67 for SNP rs1128127 (95% CI 0.45-0.99, P = 0.05), after adjustment
      for possible confounding factors. The first two SNPs (rs2706384 and rs1805015)
      are within loci involved in pro-inflammatory (interferon-gamma) and anti
      inflammatory (IL-4) cytokine responses. The third locus encodes a protein
      involved in the degradation of misfolded proteins within the endoplasmic
      reticulum, and its role, if any, in the clearance phenotype is unclear.
      CONCLUSIONS: The study showed significant association of three loci in the human
      genome with the ability of parasite to clear drug-resistant P. falciparum in
      samples taken from five countries distributed across sub-Saharan Africa. Both SNP
      rs2706384 and SNP1805015 have previously been reported to be associated with risk
      of malaria infection in African populations. The loci are involved in the Th1/Th2
      balance, and the association of SNPs within these genes suggests a key role for
      antibody in the clearance of drug-resistant parasites. It is possible that
      patients able to clear drug-resistant infections have an enhanced ability to
      control parasite growth.

PMID- 21867553
TI  - Adrenal suppression: A practical guide to the screening and management of this
      under-recognized complication of inhaled corticosteroid therapy.
AB  - Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory agents
      available for the treatment of asthma and represent the mainstay of therapy for
      most patients with the disease. Although these medications are considered safe at
      low-to-moderate doses, safety concerns with prolonged use of high ICS doses
      remain; among these concerns is the risk of adrenal suppression (AS). AS is a
      condition characterized by the inability to produce adequate amounts of the
      glucocorticoid, cortisol, which is critical during periods of physiological
      stress. It is a proven, yet under-recognized, complication of most forms of
      glucocorticoid therapy that can persist for up to 1 year after cessation of
      corticosteroid treatment. If left unnoticed, AS can lead to significant morbidity
      and even mortality. More than 60 recent cases of AS have been described in the
      literature and almost all cases have involved children being treated with >=500
      MUg/day of fluticasone.The risk for AS can be minimized through increased
      awareness and early recognition of at-risk patients, regular patient follow-up to
      ensure that the lowest effective ICS doses are being utilized to control asthma
      symptoms, and by choosing an ICS medication with minimal adrenal effects.
      Screening for AS should be considered in any child with symptoms of AS, children
      using high ICS doses, or those with a history of prolonged oral corticosteroid
      use. Cases of AS should be managed in consultation with a pediatric
      endocrinologist whenever possible. In patients with proven AS, stress steroid
      dosing during times of illness or surgery is needed to simulate the protective
      endogenous elevations in cortisol levels that occur with physiological
      stress.This article provides an overview of current literature on AS as well as
      practical recommendations for the prevention, screening and management of this
      serious complication of ICS therapy.

PMID- 21867554
TI  - Antimicrobial and toxicological activities of five medicinal plant species from
      Cameroon traditional medicine.
AB  - BACKGROUND: Infectious diseases caused by multiresistant microbial strains are on
      the increase. Fighting these diseases with natural products may be more
      efficacious. The aim of this study was to investigate the in vitro antimicrobial
      activity of methanolic, ethylacetate (EtOAc) and hexanic fractions of five
      Cameroonian medicinal plants (Piptadeniastum africana, Cissus aralioides, Hileria
      latifolia, Phyllanthus muellerianus and Gladiolus gregasius) against 10
      pathogenic microorganisms of the urogenital and gastrointestinal tracts. METHODS:
      The fractions were screened for their chemical composition and in vivo acute
      toxicity was carried out on the most active extracts in order to assess their
      inhibitory selectivity. The agar well-diffusion and the micro dilution methods
      were used for the determination of the inhibition diameters (ID) and Minimum
      inhibitory concentrations (MIC) respectively on 8 bacterial species including two
      Gram positive species (Staphylococcus aureus, Enterococcus faecalis), and six
      Gram negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,
      Proteus mirabilis, Shigella flexneri, Salmonella typhi) and two fungal isolates
      (Candida albicans, Candida krusei). The chemical composition was done according
      to Harbone (1976), the acute toxicity evaluation according to WHO protocol and
      the hepatic as well as serum parameters measured to assess liver and kidney
      functions. RESULTS: The chemical components of each plant's extract varied
      according to the solvent used, and they were found to contain alkaloids,
      flavonoids, polyphenols, triterpens, sterols, tannins, coumarins, glycosides,
      cardiac glycosides and reducing sugars. The methanolic and ethylacetate extracts
      of Phyllanthus muellerianus and Piptadeniastum africana presented the highest
      antimicrobial activities against all tested microorganisms with ID varying from 8
      to 26 mm and MIC from 2.5 to 0.31 mg/ml. The in vivo acute toxicity study carried
      out on the methanolic extracts of Phyllanthus muellerianus and Piptadeniastrum
      africana indicated that these two plants were not toxic. At the dose of 4 g/kg
      body weight, kidney and liver function tests indicated that these two medicinal
      plants induced no adverse effect on these organs. CONCLUSION: These results
      showed that, all these plant's extracts can be used as antimicrobial
      phytomedicines which can be therapeutically used against infections caused by
      multiresistant agents. Phyllanthus muellerianus, Piptadeniastum africana,
      antimicrobial, acute toxicity, kidney and liver function tests, Cameroon
      Traditional Medicine.

PMID- 21867555
TI  - Brain pericytes among cells constituting the blood-brain barrier are highly
      sensitive to tumor necrosis factor-alpha, releasing matrix metalloproteinase-9
      and migrating in vitro.
AB  - BACKGROUND: Increased matrix metalloproteinase (MMP)-9 in the plasma and brain is
      associated with blood-brain barrier (BBB) disruption through proteolytic activity
      in neuroinflammatory diseases. MMP-9 is present in the brain microvasculature and
      its vicinity, where brain microvascular endothelial cells (BMECs), pericytes and
      astrocytes constitute the BBB. Little is known about the cellular source and role
      of MMP-9 at the BBB. Here, we examined the ability of pericytes to release MMP-9
      and migrate in response to inflammatory mediators in comparison with BMECs and
      astrocytes, using primary cultures isolated from rat brains. METHODS: The culture
      supernatants were collected from primary cultures of rat brain endothelial cells,
      pericytes, or astrocytes. MMP-9 activities and levels in the supernatants were
      measured by gelatin zymography and western blot, respectively. The involvement of
      signaling molecules including mitogen-activated protein kinases (MAPKs) and
      phosphoinositide-3-kinase (PI3K)/Akt in the mediation of tumor necrosis factor
      (TNF)-alpha-induced MMP-9 release was examined using specific inhibitors. The
      functional activity of MMP-9 was evaluated by a cell migration assay. RESULTS:
      Zymographic and western blot analyses demonstrated that TNF-alpha stimulated
      pericytes to release MMP-9, and this release was much higher than from BMECs or
      astrocytes. Other inflammatory mediators [interleukin (IL)-1beta, interferon
      gamma, IL-6 and lipopolysaccharide] failed to induce MMP-9 release from
      pericytes. TNF-alpha-induced MMP-9 release from pericytes was found to be
      mediated by MAPKs and PI3K. Scratch wound healing assay showed that in contrast
      to BMECs and astrocytes the extent of pericyte migration was significantly
      increased by TNF-alpha. This pericyte migration was inhibited by anti-MMP-9
      antibody. CONCLUSION: These findings suggest that pericytes are most sensitive to
      TNF-alpha in terms of MMP-9 release, and are the major source of MMP-9 at the
      BBB. This pericyte-derived MMP-9 initiated cellular migration of pericytes, which
      might be involved in pericyte loss in the damaged BBB.

PMID- 21867556
TI  - Isolated angiitis of the central nervous system with tumor-like lesion, mimicking
      brain malignant glioma: a case report and review of the literature.
AB  - BACKGROUND: Isolated angiitis of the central nervous system (IACNS) is a rare but
      severe vascular disease, which could present like an isolated inflammatory lesion
      on magnetic resonance imaging (MRI). To date, only a few such cases with tumor
      like IACNS have been reported. CASE PRESENTATION: A 35-year-old woman presented
      with headache and left-sided weakness. MRI scans initially mislead us to a
      diagnosis of glioblastoma (GBM). Surgery was performed. The mass was sub-totally
      resected. Pathological examination confirmed a cerebral vasculitis. Radiological
      features, such as disproportionate mass effect, striped hemorrhage and abnormal
      enhancement of adjacent vessels, could be helpful to distinguish a tumor-like
      IACNS from a GBM. Single therapy with high doses of steroid did not improve the
      patient's condition. Combined therapy with prednisolone and cyclophosphamide
      showed great benefit to the patient. No relapse occurred during the period of 18
      months follow-up. CONCLUSIONS: Although a tumor-like IACNS has no established
      imaging features, a diagnosis of tumor-like IACNS should be suspected when MRI
      shows inappropriate presentations of a tumor. Greater awareness of this potential
      manifestation of IACNS may facilitate more prompt diagnosis and treatment.

PMID- 21867557
TI  - Analysis of human meiotic recombination events with a parent-sibling tracing
      approach.
AB  - BACKGROUND: Meiotic recombination ensures that each child inherits distinct
      genetic materials from each parent, but the distribution of crossovers along
      meiotic chromosomes remains difficult to identify. In this study, we developed a
      parent-sibling tracing (PST) approach from previously reported methods to
      identify meiotic crossover sites of GEO GSE6754 data set. This approach requires
      only the single nucleotide polymorphism (SNP) data of the pedigrees of both
      parents and at least two of children. RESULTS: Compared to other SNP-based
      algorithms (identity by descent or pediSNP), fewer uninformative SNPs were
      derived with the use of PST. Analysis of a GEO GSE6754 data set containing 2,145
      maternal and paternal meiotic events revealed that the pattern and distribution
      of paternal and maternal recombination sites vary along the chromosomes. Lower
      crossover rates near the centromeres were more prominent in males than in
      females. Based on analysis of repetitive sequences, we also showed that
      recombination hotspots are positively correlated with SINE/MIR repetitive
      elements and negatively correlated with LINE/L1 elements. The number of meiotic
      recombination events was positively correlated with the number of shorter tandem
      repeat sequences. CONCLUSIONS: The advantages of the PST approach include the
      ability to use only two-generation pedigrees with two siblings and the ability to
      perform gender-specific analyses of repetitive elements and tandem repeat
      sequences while including fewer uninformative SNP regions in the results.

PMID- 21867559
TI  - Assessment of an in vitro whole cigarette smoke exposure system: The Borgwaldt
      RM20S 8-syringe smoking machine.
AB  - BACKGROUND: There have been many recent developments of in vitro cigarette smoke
      systems closely replicating in vivo exposures. The Borgwaldt RM20S smoking
      machine (RM20S) enables the serial dilution and delivery of cigarette smoke to
      exposure chambers for in vitro analyses. In this study we have demonstrated
      reliability and robustness testing of the RM20S in delivering smoke to in vitro
      cultures using an in-house designed whole smoke exposure chamber. RESULTS: The
      syringe precision and accuracy of smoke dose generated by the RM20S was assessed
      using a methane gas standard and resulted in a repeatability error of <=9%.
      Differential electrical mobility particle spectrometry (DMS) measured smoke
      particles generated from reference 3R4F cigarettes at points along the RM20S. 53%
      +/- 5.9% of particles by mass reached the chamber, the remainder deposited in the
      syringe or connecting tubing and ~16% deposited in the chamber.
      Spectrofluorometric quantification of particle deposition within chambers
      indicated a positive correlation between smoke concentration and particle
      deposition. In vitro air-liquid interface (ALI) cultures (H292 lung epithelial
      cells), exposed to whole smoke (1:60 dilution (smoke:air, equivalent to ~5
      MUg/cm2)) demonstrated uniform smoke delivery within the chamber. CONCLUSIONS:
      These results suggest this smoke exposure system is a reliable and repeatable
      method of generating and exposing ALI in vitro cultures to cigarette smoke. This
      system will enable the evaluation of future tobacco products and individual
      components of cigarette smoke and may be used as an alternative in vitro tool for
      evaluating other aerosols and gaseous mixtures such as air pollutants, inhaled
      pharmaceuticals and cosmetics.

PMID- 21867558
TI  - Global transcriptome analysis of two ameiotic1 alleles in maize anthers: defining
      steps in meiotic entry and progression through prophase I.
AB  - BACKGROUND: Developmental cues to start meiosis occur late in plants. Ameiotic1
      (Am1) encodes a plant-specific nuclear protein (AM1) required for meiotic entry
      and progression through early prophase I. Pollen mother cells (PMCs) remain
      mitotic in most am1 mutants including am1-489, while am1-praI permits meiotic
      entry but PMCs arrest at the leptotene/zygotene (L/Z) transition, defining the
      roles of AM1 protein in two distinct steps of meiosis. To gain more insights into
      the roles of AM1 in the transcriptional pre-meiotic and meiotic programs, we
      report here an in depth analysis of gene expression alterations in carefully
      staged anthers at 1 mm (meiotic entry) and 1.5 mm (L/Z) caused by each of these
      am1 alleles. RESULTS: 1.0 mm and 1.5 mm anthers of am1-489 and am1-praI were
      profiled in comparison to fertile siblings on Agilent(r) 4 * 44 K microarrays.
      Both am1-489 and am1-praI anthers are cytologically normal at 1.0 mm and show
      moderate transcriptome alterations. At the 1.5-mm stage both mutants are aberrant
      cytologically, and show more drastic transcriptome changes. There are
      substantially more absolute On/Off and twice as many differentially expressed
      genes (sterile versus fertile) in am1-489 than in am1-praI. At 1.5 mm a total of
      4,418 genes are up- or down-regulated in either am1-489 or am1-praI anthers.
      These are predominantly stage-specific transcripts. Many putative meiosis-related
      genes were found among them including a small subset of allele-specific, mis
      regulated genes specific to the PMCs. Nearly 60% of transcriptome changes in the
      set of transcripts mis-regulated in both mutants (N = 530) are enriched in PMCs,
      and only 1% are enriched in the tapetal cell transcriptome. All array data
      reported herein will be deposited and accessible at MaizeGDB
      http://www.maizegdb.org/. CONCLUSIONS: Our analysis of anther transcriptome
      modulations by two distinct am1 alleles, am1-489 and am1-praI, redefines the role
      of AM1 as a modulator of expression of a subset of meiotic genes, important for
      meiotic progression and provided stage-specific insights into the genetic
      networks associated with meiotic entry and early prophase I progression.

PMID- 21867560
TI  - Advances in the treatment of chronic myeloid leukemia.
AB  - Although imatinib is firmly established as an effective therapy for newly
      diagnosed patients with chronic myeloid leukemia (CML), the field continues to
      advance on several fronts. In this minireview we cover recent results of second
      generation tyrosine kinase inhibitors in newly diagnosed patients, investigate
      the state of strategies to discontinue therapy and report on new small molecule
      inhibitors to tackle resistant disease, focusing on agents that target the T315I
      mutant of BCR-ABL. As a result of these advances, standard of care in frontline
      therapy has started to gravitate toward dasatinib and nilotinib, although more
      observation is needed to fully support this. Stopping therapy altogether remains
      a matter of clinical trials, and more must be learned about the mechanisms
      underlying the persistence of leukemic cells with treatment. However, there is
      good news for patients with the T315I mutation, as effective drugs such as
      ponatinib are on their way to regulatory approval. Despite these promising data,
      accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL
      independent resistance.

PMID- 21867561
TI  - Evaluation of two commercial global miRNA expression profiling platforms for
      detection of less abundant miRNAs.
AB  - BACKGROUND: microRNAs (miRNA) are short, endogenous transcripts that negatively
      regulate the expression of specific mRNA targets. miRNAs are found both in
      tissues and body fluids such as plasma. A major perspective for the use of miRNAs
      in the clinical setting is as diagnostic plasma markers for neoplasia. While
      miRNAs are abundant in tissues, they are often scarce in plasma. For
      quantification of miRNA in plasma it is therefore of importance to use a platform
      with high sensitivity and linear performance in the low concentration range. This
      motivated us to evaluate the performance of three commonly used commercial miRNA
      quantification platforms: GeneChip miRNA 2.0 Array, miRCURY Ready-to-Use PCR,
      Human panel I+II V1.M, and TaqMan Human MicroRNA Array v3.0. RESULTS: Using
      synthetic miRNA samples and plasma RNA samples spiked with different ratios of
      174 synthetic miRNAs we assessed the performance characteristics reproducibility,
      recovery, specificity, sensitivity and linearity. It was found that while the qRT
      PCR based platforms were sufficiently sensitive to reproducibly detect miRNAs at
      the abundance levels found in human plasma, the array based platform was not. At
      high miRNA levels both qRT-PCR based platforms performed well in terms of
      specificity, reproducibility and recovery. At low miRNA levels, as in plasma, the
      miRCURY platform showed better sensitivity and linearity than the TaqMan
      platform. CONCLUSION: For profiling clinical samples with low miRNA abundance,
      such as plasma samples, the miRCURY platform with its better sensitivity and
      linearity would probably be superior.

PMID- 21867562
TI  - Knowledge, attitudes and practices of health professionals and women towards
      medication use in breastfeeding: A review.
AB  - Many breastfeeding women require and regularly take medicines, especially those
      available over-the-counter, and the safe use of these is dependent on the advice
      provided by health professionals such as general practitioners and pharmacists.
      The primary aim of this review therefore, was to investigate the literature
      relating to health professionals' and women's knowledge, attitudes and practices
      towards medication use and safety in breastfeeding. The limited literature that
      was uncovered identified that general practitioners and pharmacists have poor
      knowledge, but positive attitudes, and variable practices that are mostly guided
      by personal experience. They tend to make decisions about the use of a medicine
      whilst breastfeeding based on the potential 'risk' that it poses to the infant in
      terms of possible adverse reactions, rather than its 'compatibility' with breast
      milk. The decision-making process between health professionals and women is
      usually not a negotiated process, and women are often asked to stop breastfeeding
      whilst taking a medicine. Women, in turn, are left dissatisfied with the advice
      received, many choosing not to initiate therapy or not to continue breastfeeding.
      Some directions for future research have been suggested to address the issues
      identified in this critical area. This review is important from a societal
      perspective because many breastfeeding women require and regularly take
      medications, especially those available without prescription, and the safe use of
      these is dependent on the advice provided by health professionals, which is
      ultimately influenced by their knowledge, attitudes and practices. However, there
      is an absence of high quality evidence from randomised controlled trials on the
      safety of medications taken during breastfeeding, which naturally would hinder
      health professionals from appropriately advising women. It is equally important
      to know about women's experiences of advice received from health professionals,
      and whether there is consistency between recommendations made across resources on
      medication safety in breastfeeding, in order to gain a full understanding of the
      issues prevalent in this area of practice.

PMID- 21867563
TI  - Clusters of spatial, temporal, and space-time distribution of hemorrhagic fever
      with renal syndrome in Liaoning Province, Northeastern China.
AB  - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne
      disease caused by Hantavirus, with characteristics of fever, hemorrhage, kidney
      damage, and hypotension. HFRS is recognized as a notifiable public health problem
      in China, and Liaoning Province is one of the most seriously affected areas with
      the most cases in China. It is necessary to investigate the spatial, temporal,
      and space-time distribution of confirmed cases of HFRS in Liaoning Province,
      China for future research into risk factors. METHODS: A cartogram map was
      constructed; spatial autocorrelation analysis and spatial, temporal, and space
      time cluster analysis were conducted in Liaoning Province, China over the period
      1988-2001. RESULTS: When the number of permutation test was set to 999, Moran's I
      was 0.3854, and was significant at significance level of 0.001. Spatial cluster
      analysis identified one most likely cluster and four secondary likely clusters.
      Temporal cluster analysis identified 1998-2001 as the most likely cluster. Space
      time cluster analysis identified one most likely cluster and two secondary likely
      clusters. CONCLUSIONS: Spatial, temporal, and space-time scan statistics may be
      useful in supervising the occurrence of HFRS in Liaoning Province, China. The
      result of this study can not only assist health departments to develop a better
      prevention strategy but also potentially increase the public health
      intervention's effectiveness.

PMID- 21867564
TI  - Acute heart failure caused by a giant hepatocellular metastatic tumor of the
      right atrium.
AB  - We present a symptomatic 40-year-old cirrhotic man who presented with sudden
      onsets of syncope. Echocardiography revealed right ventricular outflow track
      obstruction caused by a huge right atrial mass. The tumor was surgically excised
      under cardiopulmonary bypass. Although no primary cancerous lesion in the liver
      was detected, histopathology revealed that the mass was a metastatic
      hepatocellular carcinoma. The aim of this report is to show the value of urgent
      preoperative computed tomography and its contribution in the operative strategy.
      The importance of urgent surgical treatment with tricuspid valve sparing tumor
      resection is emphasized even though the prognosis for such patients is dismal. We
      also discuss the further management options of such rare cases.

PMID- 21867566
TI  - Severe anaemia is associated with a higher risk for preeclampsia and poor
      perinatal outcomes in Kassala hospital, eastern Sudan.
AB  - BACKGROUND: Anaemia during pregnancy is major health problem. There is
      conflicting literature regarding the association between anaemia and its severity
      and maternal and perinatal outcomes. METHODS: This is a retrospective case
      control study conducted at Kassala hospital, eastern Sudan. Medical files of
      pregnant women with severe anaemia (haemoglobin (Hb) < 7 g/dl, n = 303) who
      delivered from January 2008 to December 2010 were reviewed. Socio-demographic and
      obstetric data were analysed and compared with a similar number of women with
      mild/moderate anaemia (Hb = 7-10.9 g/dl, n = 303) and with no anaemia (Hb > 11
      g/dl, n = 303). Logistic regression analysis was performed separately for each of
      the outcome measures: preeclampsia, eclampsia, preterm birth, low birth weight
      (LBW) and stillbirth. RESULTS: There were 9578 deliveries at Kassala hospital,
      4012 (41.8%) women had anaemia and 303 (3.2%) had severe anaemia. The corrected
      risk for preeclampsia increased only in severe anaemia (OR = 3.6, 95% CI: 1.4
      9.1, P = 0.007). Compared with women with no anaemia, the risk of LBW was 2.5
      times higher in women with mild/moderate anaemia (95% CI: 1.1-5.7), and 8.0 times
      higher in women with severe anaemia (95% CI: 3.8-16.0). The risk of preterm
      delivery increased significantly with the severity of anaemia (OR = 3.2 for women
      with mild/moderate anaemia and OR = 6.6 for women with severe anaemia, compared
      with women with no anaemia). The corrected risk for stillbirth increased only in
      severe anaemia (OR = 4.3, 95% CI: 1.9-9.1, P < 0.001). CONCLUSIONS: The greater
      the severity of the anaemia during pregnancy, the greater the risk of
      preeclampsia, preterm delivery, LBW and stillbirth. Preventive measures should be
      undertaken to decrease the prevalence of anaemia in pregnancy.

PMID- 21867565
TI  - Temporal trends and recent correlates in sedentary behaviours in Chinese
      children.
AB  - BACKGROUND: Sedentary behaviours (television, video and computer) are related to
      health outcomes independent of physical activity. Few studies have examined
      trends and correlates of sedentary behaviours among youth in developing nations.
      The current study is to examine temporal trends in sedentary behaviours and
      recent correlates of screen use in Chinese children during a period of economic
      transition. METHODS: Secondary analysis of China Health and Nutrition Surveys.
      Cross-sectional data on sedentary behaviours including screen use among children
      aged 6-18 years from four surveys in 1997 (n = 2,469), 2000 (n = 1,838), 2004 (n
      = 1,382) and 2006 (n = 1,128). Temporal trends in screen use by socio-demographic
      characteristics were examined. The correlates of spending more than 2 hours per
      day on screen time in the most recent survey data (2006, n = 986) were analysed
      using survey logistic regression analysis. RESULTS: Daily screen time
      significantly increased in each subgroup by age, sex and urban/rural residence,
      with the largest increase for urban boys aged 13-18 years from 0.5 hours to 1.7
      hours, and for rural boys aged 6-12 years from 0.7 hours to 1.7 hours (p <
      0.0001). Daily time in both homework and extracurricular cultural activity
      increased significantly from 2000 to 2004 but was stable from 2004 to 2006. Boys
      (OR: 1.41, 95%CI: 1.09 -1.82), having a TV in the bedroom (OR: 1.86, 95%CI: 1.15 
      3.01), having access to internet at home (OR: 1.93, 95%CI: 1.12 - 3.31) or at
      internet cafes (OR: 2.01, 95%CI: 1.21 - 3.34), or often watching TV with parents
      (OR: 2.27, 95%CI: 1.37 - 3.74) were all associated with being more likely to be
      high screen users (>= 2 hours/day). While children aged 13-18 years (OR: 0.67,
      95%CI: 0.46-0.97) were less likely to be high screen users. Children whose
      parents often have rules on their TV viewing (OR: 0.64, 95%CI: 0.37 - 1.10) were
      slightly but not significantly less likely to be high screen users. CONCLUSION:
      This study confirms sedentary behaviour has increased over the last decade in
      Chinese children. Efforts to ensure Chinese youth meet screen time guidelines
      include limiting access to screen technologies and encouraging parents to monitor
      their own screen time and to set limits on their child's screen time.

PMID- 21867567
TI  - Brain-computer interface controlled functional electrical stimulation system for
      ankle movement.
AB  - BACKGROUND: Many neurological conditions, such as stroke, spinal cord injury, and
      traumatic brain injury, can cause chronic gait function impairment due to foot
      drop. Current physiotherapy techniques provide only a limited degree of motor
      function recovery in these individuals, and therefore novel therapies are needed.
      Brain-computer interface (BCI) is a relatively novel technology with a potential
      to restore, substitute, or augment lost motor behaviors in patients with
      neurological injuries. Here, we describe the first successful integration of a
      noninvasive electroencephalogram (EEG)-based BCI with a noninvasive functional
      electrical stimulation (FES) system that enables the direct brain control of foot
      dorsiflexion in able-bodied individuals. METHODS: A noninvasive EEG-based BCI
      system was integrated with a noninvasive FES system for foot dorsiflexion.
      Subjects underwent computer-cued epochs of repetitive foot dorsiflexion and
      idling while their EEG signals were recorded and stored for offline analysis. The
      analysis generated a prediction model that allowed EEG data to be analyzed and
      classified in real time during online BCI operation. The real-time online
      performance of the integrated BCI-FES system was tested in a group of five able
      bodied subjects who used repetitive foot dorsiflexion to elicit BCI-FES mediated
      dorsiflexion of the contralateral foot. RESULTS: Five able-bodied subjects
      performed 10 alternations of idling and repetitive foot dorsifiexion to trigger
      BCI-FES mediated dorsifiexion of the contralateral foot. The epochs of BCI-FES
      mediated foot dorsifiexion were highly correlated with the epochs of voluntary
      foot dorsifiexion (correlation coefficient ranged between 0.59 and 0.77) with
      latencies ranging from 1.4 sec to 3.1 sec. In addition, all subjects achieved a
      100% BCI-FES response (no omissions), and one subject had a single false alarm.
      CONCLUSIONS: This study suggests that the integration of a noninvasive BCI with a
      lower-extremity FES system is feasible. With additional modifications, the
      proposed BCI-FES system may offer a novel and effective therapy in the neuro
      rehabilitation of individuals with lower extremity paralysis due to neurological
      injuries.

PMID- 21867569
TI  - Traumatic brain injury and resuscitation with blood products: what should we do?
AB  - The study by Dr Peiniger and colleagues in a recent issue of Critical Care
      indicates that transfusion strategies using an early and more balanced ratio
      between fresh frozen plasma and red blood cell transfusions provide a survival
      benefit in patients with acute traumatic coagulopathy requiring massive
      transfusion within the first 24 hours of hospitalization. However, this topic has
      never been explored in depth in patients with concomitant severe traumatic brain
      injury. While the study is retrospective and certainly not a substitute for a
      well-designed prospective trial, the authors nonetheless should be commended for
      addressing this issue with their current work. Currently, the optimum fluid
      resuscitation paradigm for patients with both severe traumatic brain injury and
      other injuries requiring significant volume resuscitation is not clear.

PMID- 21867568
TI  - Atg8: an autophagy-related ubiquitin-like protein family.
AB  - Autophagy-related (Atg) proteins are eukaryotic factors participating in various
      stages of the autophagic process. Thus far 34 Atgs have been identified in yeast,
      including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin
      like proteins that share a similar structure consisting of two amino-terminal
      alpha helices and a ubiquitin-like core. Atg8 family members are expressed in
      various tissues, where they participate in multiple cellular processes, such as
      intracellular membrane trafficking and autophagy. Their role in autophagy has
      been intensively studied. Atg8 proteins undergo a unique ubiquitin-like
      conjugation to phosphatidylethanolamine on the autophagic membrane, a process
      essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many
      other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular
      animals can be divided, by sequence similarities, into three subfamilies:
      microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), gamma
      aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated
      ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians
      (such as sea anemones, corals and hydras) and bilateral animals. Although genes
      from all three subfamilies are found in vertebrates, some invertebrate lineages
      have lost the genes from one or two subfamilies. The amino terminus of Atg8
      proteins varies between the subfamilies and has a regulatory role in their
      various functions. Here we discuss the evolution of Atg8 proteins and summarize
      the current view of their function in intracellular trafficking and autophagy
      from a structural perspective.

PMID- 21867570
TI  - The real cost of sequencing: higher than you think!
AB  - Advances in sequencing technology have led to a sharp decrease in the cost of
      'data generation'. But is this sufficient to ensure cost-effective and efficient
      'knowledge generation'?

PMID- 21867572
TI  - NF-kappaB, stem cells and breast cancer: the links get stronger.
AB  - Self-renewing breast cancer stem cells are key actors in perpetuating tumour
      existence and in treatment resistance and relapse. The molecular pathways
      required for their maintenance are starting to be elucidated. Among them is the
      transcription factor NF-kappaB, which is known to play critical roles in cell
      survival, inflammation and immunity. Recent studies indicate that mammary
      epithelial NF-kappaB regulates the self-renewal of breast cancer stem cells in a
      model of Her2-dependent tumourigenesis. We will describe here the NF-kappaB
      activating pathways that are involved in this process and in which progenitor
      cells this transcription factor is actually activated.

PMID- 21867571
TI  - Understanding the Warburg effect and the prognostic value of stromal caveolin-1
      as a marker of a lethal tumor microenvironment.
AB  - Cancer cells show a broad spectrum of bioenergetic states, with some cells using
      aerobic glycolysis while others rely on oxidative phosphorylation as their main
      source of energy. In addition, there is mounting evidence that metabolic coupling
      occurs in aggressive tumors, between epithelial cancer cells and the stromal
      compartment, and between well-oxygenated and hypoxic compartments. We recently
      showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and
      mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor
      progression. More specifically , increased autophagy/mitophagy in the tumor
      stroma drives a form of parasitic epithelial-stromal metabolic coupling. These
      findings explain why it is effective to treat tumors with either inducers or
      inhibitors of autophagy, as both would disrupt this energetic coupling. We also
      discuss evidence that glutamine addiction in cancer cells produces ammonia via
      oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn,
      could then help maintain autophagy in the tumor stromal compartment. In this
      vicious cycle, the initial glutamine provided to cancer cells would be produced
      by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial
      stromal metabolic coupling has important implications for cancer diagnosis and
      therapy, for example, in designing novel metabolic imaging techniques and
      establishing new targeted therapies. In direct support of this notion, we
      identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia,
      and autophagy in the tumor microenvironment, explaining its powerful predictive
      value. Loss of stromal caveolin-1 in breast cancers is associated with early
      tumor recurrence, metastasis, and drug resistance, leading to poor clinical
      outcome.

PMID- 21867573
TI  - Capturing Alzheimer's disease genomes with induced pluripotent stem cells:
      prospects and challenges.
AB  - A crucial limitation to our understanding of Alzheimer's disease (AD) is the
      inability to test hypotheses on live, patient-specific neurons. Patient autopsies
      are limited in supply and only reveal endpoints of disease. Rodent models
      harboring familial AD mutations lack important pathologies, and animal models
      have not been useful in modeling the sporadic form of AD because of complex
      genetics. The recent development of induced pluripotent stem cells (iPSCs)
      provides a method to create live, patient-specific models of disease and to
      investigate disease phenotypes in vitro. In this review, we discuss the genetics
      of AD patients and the potential for iPSCs to capture the genomes of these
      individuals and generate relevant cell types. Specifically, we examine recent
      insights into the genetic fidelity of iPSCs, advances in the area of neuronal
      differentiation, and the ability of iPSCs to model neurodegenerative diseases.

PMID- 21867574
TI  - Towards the integration of genomics, epidemiological and clinical data.
AB  - A report on 'A Wellcome Trust Scientific Conference: Applied Bioinformatics and
      Public Health Microbiology 2011', Hinxton, Cambridge, 1-3 June, 2011.

PMID- 21867575
TI  - Systems medicine and the public's health.
AB  - Innovative 'systems' approaches to biomedical research offer substantial promise
      for advancing knowledge and improving health care, as outlined by Bousquet et al.
      in this issue. However, they are unlikely to improve population health without
      concurrent efforts to address environmental and social contributors to health,
      including conditions such as poverty, substandard housing, and restricted access
      to employment and education. Biomedical researchers have a responsibility to
      promote realistic expectations for systems or 'P4' medicine, and to join others
      in calling for broad efforts to promote equitable access to health care and
      social conditions that promote well-being.See correspondence article:
      http://genomemedicine.com/content/3/7/43.

PMID- 21867576
TI  - Investigating preference-performance relationships in aboveground-belowground
      life cycles: a laboratory and field study with the vine weevil (Otiorhynchus
      sulcatus).
AB  - The preference-performance hypothesis has principally considered insect
      herbivores with aboveground lifecycles, although the hypothesis could be equally
      relevant to insects with life stages occurring both aboveground and belowground.
      Moreover, most studies have focussed on either laboratory or field experiments,
      with little attempt to relate the two. In this study, the preference-performance
      hypothesis was examined in an aboveground-belowground context in the laboratory
      using the vine weevil (Otiorhynchus sulcatus (F.)) (Coleoptera: Curculionidae)
      and two cultivars of red raspberry (Rubus idaeus), Glen Rosa and Glen Ample. A
      two-year field study (2008-2009) was also undertaken to characterise the
      population dynamics of adult weevils on the two raspberry cultivars. Larval
      performance (abundance and mass) differed significantly between Glen Rosa and
      Glen Ample, with Glen Rosa resulting in 26% larger but 56% fewer larvae compared
      to Glen Ample. Larval abundances were significantly and positively correlated
      with root nitrogen and magnesium concentrations, but negatively correlated with
      root iron. However, concentrations of these minerals were not significantly
      different in the two cultivars. Adult weevils did not preferentially select
      either of the two cultivars for egg laying (laying 3.08 and 2.80 eggs per day on
      Glen Ample and Glen Rosa, respectively), suggesting that there was no strong
      preference-performance relationship between adult vine weevils and their
      belowground offspring. Field populations of adult vine weevils were significantly
      higher on Glen Ample than Glen Rosa, which may reflect the higher larval survival
      on Glen Ample observed in laboratory experiments.

PMID- 21867577
TI  - Wing shape as a potential discriminator of morphologically similar pest taxa
      within the Bactrocera dorsalis species complex (Diptera: Tephritidae).
AB  - Four morphologically cryptic species of the Bactrocera dorsalis fruit fly complex
      (B. dorsalis s.s., B. papayae, B. carambolae and B. philippinensis) are serious
      agricultural pests. As they are difficult to diagnose using traditional taxonomic
      techniques, we examined the potential for geometric morphometric analysis of wing
      size and shape to discriminate between them. Fifteen wing landmarks generated
      size and shape data for 245 specimens for subsequent comparisons among three
      geographically distinct samples of each species. Intraspecific wing size was
      significantly different within samples of B. carambolae and B. dorsalis s.s. but
      not within samples of B. papayae or B. philippinensis. Although B. papayae had
      the smallest wings (average centroid size=6.002 mm+/-0.061 SE) and B. dorsalis
      s.s. the largest (6.349 mm+/-0.066 SE), interspecific wing size comparisons were
      generally non-informative and incapable of discriminating species. Contrary to
      the wing size data, canonical variate analysis based on wing shape data
      discriminated all species with a relatively high degree of accuracy; individuals
      were correctly reassigned to their respective species on average 93.27% of the
      time. A single sample group of B. carambolae from locality 'TN Malaysia' was the
      only sample to be considerably different from its conspecific groups with regards
      to both wing size and wing shape. This sample was subsequently deemed to have
      been originally misidentified and likely represents an undescribed species. We
      demonstrate that geometric morphometric techniques analysing wing shape represent
      a promising approach for discriminating between morphologically cryptic taxa of
      the B. dorsalis species complex.

PMID- 21867578
TI  - Effect of dietary supplementation with unprocessed and ethanol-extracted apple
      pomaces on caecal fermentation, antioxidant and blood biomarkers in rats.
AB  - The present 4-week study on growing Wistar rats was aimed at assessing the
      potential advantages of dietary supplementation with apple pomace containing both
      fibre and polyphenols, which enables nutritional exploitation of the
      physiological traits of both compounds. A total of twenty-four rats, assigned to
      the control (C), group fed with a diet supplemented with 14% of processed apple
      pomace (A) and group fed with a diet supplemented with 15% unprocessed apple
      pomace (AP) groups, were fed the following iso-fibrous diets: control, ethanol
      extracted and unprocessed apple pomaces (low and high level of dietary
      polyphenols, i.e. 0.002 and 0.018%, respectively). To measure the animal
      response, parameters describing the caecal fermentation, antioxidative status and
      lipoprotein profile of rats were assessed. Both dietary apple pomaces were found
      to significantly (P<=0.05) decrease caecal pH and ammonia concentration,
      microbial beta-glucuronidase activity as well as to increase caecal SCFA
      concentration in comparison to the control diet. The unprocessed pomace did not
      suppress caecal fermentation. Unlike the extracted one, the dietary apple pomace
      rich in polyphenols significantly (P<=0.05 v. C group) increased erythrocyte
      superoxide dismutase activity and serum antioxidant capacity of lipid-soluble
      substances and significantly (P<=0.05 v. C group) decreased amounts of
      thiobarbituric acid-reactive substances in liver tissue. Moreover, the 4-week
      administration of the AP diet to rats evoked a significant decrease in serum
      glucose concentration (P<=0.05 v. C and A groups). In conclusion, the results
      demonstrated that the polyphenol-rich fibre complexes from apple pomace exerted
      positive effects on gastrointestinal physiology and antioxidant status of rats.

PMID- 21867579
TI  - Diet quality and change in anthropometric measures: 15-year longitudinal study in
      Australian adults.
AB  - Evidence from longitudinal studies on the association between diet quality and
      change in anthropometric measures is scarce. We therefore investigated the
      relationship between a recently developed food-based dietary index and change in
      measured BMI and waist circumference (WC) in Australian adults (1992-2007). We
      used data from the Australian population-based Nambour Skin Cancer Study
      comprising 1231 adults aged 25-75 years at baseline (1992). We applied
      generalised estimating equations (GEE) to examine the association between diet
      quality and change in anthropometric measures. Dietary intake was assessed by an
      FFQ in 1992, 1996 and 2007. Diet quality was estimated using the dietary
      guideline index (DGI), developed to reflect the dietary guidelines for Australian
      adults; a higher score indicating increased compliance. Multivariable models,
      stratified by sex, were adjusted for sociodemographic and lifestyle
      characteristics. We show that men with higher diet quality had a lower gain in
      BMI as compared to those with low diet quality during the 15-year follow-up. In a
      multivariable adjusted model, as compared to men in quartile 1 (reference), those
      in the highest quartile had the lowest gain in BMI (mean (95 % CI): 0.05 (0.00,
      0.09) v. 0.11 (0.06, 0.16) kg/m2 per year, P =0.01). Diet quality was inversely,
      but non-significantly associated with change in WC. In women, DGI score was
      unrelated to change in any body measure. Energy underreporting did not explain
      the lack of association. We conclude that adherence to a high-quality diet
      according to Australian dietary guidelines leads to lower gain in BMI and WC in
      middle-aged men, but not in women.

PMID- 21867580
TI  - Empirically evaluating the impact of adjudicative tribunals in the health sector:
      context, challenges and opportunities.
AB  - Adjudicative tribunals are an integral part of health system governance, yet
      their real-world impact remains largely unknown. Most assessments focus on
      internal accountability and use anecdotal methodologies; few, studies if any,
      empirically evaluate their external impact and use these data to test
      effectiveness, track performance, inform service improvements and ultimately
      strengthen health systems. Given that such assessments would yield important
      benefits and have been conducted successfully in similar settings (e.g.
      specialist courts), their absence is likely attributable to complexity in the
      health system, methodological difficulties and the legal environment within which
      tribunals operate. We suggest practical steps for potential evaluators to conduct
      empirical impact evaluations along with an evaluation matrix template featuring
      possible target outcomes and corresponding surrogate endpoints, performance
      indicators and empirical methodologies. Several system-level strategies for
      supporting such assessments have also been suggested for academics, health system
      institutions, health planners and research funders. Action is necessary to ensure
      that policymakers do not continue operating without evidence but can rather
      pursue data-driven strategies that are more likely to achieve their health system
      goals in a cost-effective way.

PMID- 21867581
TI  - Nationwide study of antipsychotic use among community-dwelling persons with
      Alzheimer's disease in Finland.
AB  - BACKGROUND: Antipsychotics continue to be widely used in the treatment of
      behavioral and psychological symptoms of dementia despite their limited
      effectiveness and well-known risks, including increased mortality. Our aim was to
      investigate the national pattern of antipsychotic use among community-dwelling
      persons with and without Alzheimer's disease (AD) in Finland. METHODS: The Social
      Insurance Institution of Finland (SII) identified all persons with a verified
      diagnosis of AD in Finland on 31 December 2005. A control for each person with
      AD, matched in terms of age, sex and region of residence, was also identified.
      Data on reimbursed drug purchases in 2005 were extracted from the Finnish
      National Prescription Register. Conditional logistic regression analysis was used
      to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the use of
      antipsychotics. RESULTS: The study population comprised 28,089 matched pairs of
      persons with and without AD (mean age 80.0 years, SD 6.8, 32.2% men). The annual
      prevalence of antipsychotic use was higher among persons with than without AD
      (22.1% vs. 4.4%, adjusted OR = 5.91; 95% CI 5.91-6.31). Among persons with AD,
      the prevalence of antipsychotic use was similar across all age groups. Of the
      antipsychotic users, 85.2% with AD and 51.3% without AD purchased second
      generation antipsychotics. Most antipsychotic prescriptions - 67.8% in the AD and
      62.9% in the non-AD group - were generated in primary care situations.
      CONCLUSION: One-fifth of persons with AD used antipsychotic drugs. Antipsychotic
      use was six times more prevalent among persons with AD than without AD. Most
      antipsychotics were prescribed by primary care physicians.

PMID- 21867582
TI  - Iatrogenic injury of the chorda tympani: a systematic review.
AB  - OBJECTIVE: To review the currently available literature on iatrogenic injury of
      the adult chorda tympani. DESIGN: Systematic literature review. METHOD: Five
      electronic databases and one search engine were used to access available English
      language literature on the chorda tympani, focusing on iatrogenic injury.
      RESULTS: The chorda tympani is most often injured during middle-ear surgery,
      after which at least 15-22 per cent of patients experience symptoms, mostly
      changes in taste and dryness of the mouth. Numerous factors influence whether
      injury to the chorda tympani causes symptoms, including the extent of injury,
      type of surgery, age of the patient, anatomical variables and subjective
      adaptation. Although most patients experience gradual symptomatic recovery,
      complaints can be persistent and troublesome. CONCLUSION: Care should be taken to
      preserve the chorda tympani during middle-ear surgery, and to warn patients pre
      operatively about this potential complication. This is particularly important if
      surgery is bilateral.

PMID- 21867583
TI  - Clinical study of mucosa-associated lymphoid tissue lymphomas of the head and
      neck.
AB  - BACKGROUND: Limited information is available on mucosa-associated lymphoid tissue
      lymphomas arising in the head and neck. METHOD: A retrospective analysis was
      conducted of 20 patients who were histologically diagnosed with mucosa-associated
      lymphoid tissue lymphoma and treated at our institution between January 1990 and
      December 2009. RESULTS: Treatment consisted of surgical resection alone in two
      patients (10 per cent), surgical resection with consecutive radiotherapy in one
      (5 per cent), and radiotherapy alone in eight (40 per cent). Three patients (15
      per cent) were treated with systemic chemotherapy, and three (15 per cent)
      received chemoradiotherapy. Three patients (15 per cent) were informed of the
      diagnosis but not treated for their condition. CONCLUSION: All of the 20 patients
      were still alive after a mean follow-up period of 50.8 months. Local treatment
      for mucosa-associated lymphoid tissue lymphoma of the head and neck should be the
      first choice in early-stage disease. However, prolonged follow up is important to
      determine these patients' long-term response to treatment.

PMID- 21867584
TI  - Endoscopic devascularisation of sphenopalatine bundle in intractable posterior
      epistaxis: technique, efficacy and safety.
AB  - OBJECTIVE: To evaluate endoscopic cauterisation of the sphenopalatine
      neurovascular bundle, as treatment for intractable posterior epistaxis, with
      regard to efficacy, safety and post-operative sequelae. PATIENTS AND METHODS: A
      prospective study reviewed 42 patients with severe posterior epistaxis who were
      treated with endoscopic cauterisation of the sphenopalatine neurovascular bundle,
      over a 17-month period. RESULTS: Hypertension and hepatic disease were present as
      predisposing factors in 66.7 and 35.7 per cent of patients, respectively.
      Branching of the sphenopalatine artery at its foramen was present in more than 85
      per cent of patients. The success rate was 100 per cent, with no recurrent
      epistaxis in the follow-up period. Severe nasal dryness was present in only four
      patients (9.5 per cent); hypoaesthesia was found in the nasal mucosa of eight
      patients, without any patient complaints. CONCLUSION: Endoscopic sphenopalatine
      neurovascular bundle cauterisation is an effective treatment for refractory
      posterior epistaxis. In this study, neurovascular bundle cauterisation did not
      cause any neurological deficits or major complications.

PMID- 21867585
TI  - Quality of information available on the World Wide Web for patients undergoing
      thyroidectomy: review.
AB  - INTRODUCTION: This study aimed to assess the quality of information available on
      the World Wide Web for patients undergoing thyroidectomy. METHODS: The first 50
      web-links generated by internet searches using the five most popular search
      engines and the key word 'thyroidectomy' were evaluated using the Lida website
      validation instrument (assessing accessibility, usability and reliability) and
      the Flesch Reading Ease Score. RESULTS: We evaluated 103 of a possible 250
      websites. Mean scores (ranges) were: Lida accessibility, 48/63 (27-59); Lida
      usability, 36/54 (21-50); Lida reliability, 21/51 (4-38); and Flesch Reading
      Ease, 43.9 (2.6-77.6). CONCLUSION: The quality of internet health information
      regarding thyroidectomy is variable. High ranking and popularity are not good
      indicators of website quality. Overall, none of the websites assessed achieved
      high Lida scores. In order to prevent the dissemination of inaccurate or
      commercially motivated information, we recommend independent labelling of medical
      information available on the World Wide Web.

PMID- 21867586
TI  - Functional results of pharyngo-laryngectomy and total laryngectomy: a comparison.
AB  - OBJECTIVE: To compare the key functional results (regarding swallowing and voice
      rehabilitation) in patients treated by pharyngo-laryngectomy with flap
      reconstruction, versus standard, wide-field, total laryngectomy. METHOD: We
      studied 97 patients who had undergone total laryngectomy and pharyngo
      laryngectomy with flap reconstruction. The main outcome measures were swallowing
      (i.e. solid food, soft diet, fluid or enteral feeding) and fluent voice
      development. RESULTS: There were 79 men and 18 women, with follow up of one to 19
      years. Voice (p = 0.037) and swallowing (p = 0.041) results were significantly
      worse after circumferential pharyngo-laryngectomy than after non-circumferential
      pharyngo-laryngectomy. There was no significant difference in voice (p = 0.23) or
      swallowing (p = 0.655) results, comparing total laryngectomy and non
      circumferential pharyngo-laryngectomy. The presence of a post-operative fistula
      significantly influenced voice (p = 0.001) and swallowing (p = 0.009) outcomes.
      CONCLUSION: The additional measures involved in pharyngo-laryngectomy do not
      confer any functional disadvantage, compared with total laryngectomy, but only if
      the procedure is non-circumferential. Functional results of circumferential
      pharyngo-laryngectomy are worse than those of both non-circumferential pharyngo
      laryngectomy and total laryngectomy. If oncologically possible and safe, it is
      better to keep a pharyngo-laryngectomy non-circumferential.

PMID- 21867587
TI  - Long-term clinical results of radiofrequency tissue volume reduction for inferior
      turbinate hypertrophy.
AB  - OBJECTIVE: To investigate the long-term clinical results of radiofrequency tissue
      volume reduction for symptomatic inferior turbinate hypertrophy. STUDY DESIGN:
      Patients who were unresponsive to medical treatment (n = 197) received turbinate
      reduction using radiofrequency energy. Subjective symptoms were assessed using a
      10 cm visual analogue scale, and all patients underwent acoustic rhinometry
      before the procedure and six, 24, 48 and 60 months afterwards. RESULTS: Of the
      197 treated patients, 148 completed the protocol. No significant peri-operative
      complications were observed. Thirty-two patients required follow-up treatment.
      Significant improvements were seen in nasal obstruction and discharge scores and
      in acoustic rhinometry values, at six, 24, 48 and 60 months post-operatively,
      compared with pre-operative values (p < 0.001 and p < 0.05, respectively).
      CONCLUSION: Radiofrequency tissue volume reduction is an effective procedure for
      inferior turbinate hypertrophy. The clinical benefit of this procedure persisted
      60 months after the procedure.

PMID- 21867588
TI  - Voice function following Han's uvulopalatopharyngoplasty.
AB  - OBJECTIVE: To investigate voice function following Han's
      uvulopalatopharyngoplasty. PATIENTS AND METHODS: Acoustic and articulatory
      function was examined by acoustic analysis and by formant frequency and bandwidth
      analysis, before and after Han's uvulopalatopharyngoplasty, in 56 patients with
      obstructive sleep apnoea hypopnoea syndrome. RESULTS: These patients' normalised
      noise energy was higher than normal, and improved post-operatively. Their pre
      operative F1, F2, and F3 formant frequencies and B1 and B2 formant bandwidths
      were significantly lower than those of normal controls; however, one month after
      surgery their F1 and F2 frequencies were markedly higher. CONCLUSION: The
      acoustic and articulatory characteristics of obstructive sleep apnoea hypopnoea
      syndrome patients differed from those of normal subjects. After Han's
      uvulopalatopharyngoplasty, obstructive factors in the oropharynx were relieved,
      allowing oropharyngeal cavity expansion and a gradual increase in formant
      frequency to within the normal range. Patients' vocal quality improved and their
      resonator and articulator functions were protected and enhanced.

PMID- 21867589
TI  - Duplicate internal auditory canals with facial and vestibulocochlear nerve
      dysfunction.
AB  - OBJECTIVE: We report an extremely rare case of duplication of the internal
      auditory canal associated with dysfunction of both the facial and
      vestibulocochlear nerves. We also review the literature regarding the integrity
      of the facial and vestibulocochlear nerves in such cases. CASE REPORT: A 34-year
      old man presented with unilateral, right-sided, sensorineural hearing loss and
      facial nerve palsy since childhood. Facial nerve function was observed to be
      House-Brackmann grade III. Computed tomography and magnetic resonance imaging
      demonstrated ipsilateral duplicate, vacant internal auditory canals. Based on the
      clinical presentation, we interpreted these radiological findings as aplasia of
      the vestibulocochlear nerve and severe hypoplasia of the facial nerve.
      CONCLUSION: To our best knowledge, this is the first report of vestibulocochlear
      nerve aplasia and severe facial nerve hypoplasia in a case of ipsilateral
      duplication of the internal auditory canal. High resolution gradient echo
      magnetic resonance imaging sequences are advocated for assessment of neural
      integrity in patients with an abnormal internal auditory canal and facial and/or
      vestibulocochlear nerve dysfunction.

PMID- 21867590
TI  - The molecular systematics of blowflies and screwworm flies (Diptera:
      Calliphoridae) using 28S rRNA, COX1 and EF-1alpha: insights into the evolution of
      dipteran parasitism.
AB  - The Calliphoridae include some of the most economically significant myiasis
      causing flies in the world - blowflies and screwworm flies - with many being
      notorious for their parasitism of livestock. However, despite more than 50 years
      of research, key taxonomic relationships within the family remain unresolved.
      This study utilizes nucleotide sequence data from the protein-coding genes COX1
      (mitochondrial) and EF1alpha (nuclear), and the 28S rRNA (nuclear) gene, from 57
      blowfly taxa to improve resolution of key evolutionary relationships within the
      family Calliphoridae. Bayesian phylogenetic inference was carried out for each
      single-gene data set, demonstrating significant topological difference between
      the three gene trees. Nevertheless, all gene trees supported a Calliphorinae
      Luciliinae subfamily sister-lineage, with respect to Chrysomyinae. In addition,
      this study also elucidates the taxonomic and evolutionary status of several less
      well-studied groups, including the genus Bengalia (either within Calliphoridae or
      as a separate sister-family), genus Onesia (as a sister-genera to, or sub-genera
      within, Calliphora), genus Dyscritomyia and Lucilia bufonivora, a specialised
      parasite of frogs and toads. The occurrence of cross-species hybridisation within
      Calliphoridae is also further explored, focusing on the two economically
      significant species Lucilia cuprina and Lucilia sericata. In summary, this study
      represents the most comprehensive molecular phylogenetic analysis of family
      Calliphoridae undertaken to date.

PMID- 21867591
TI  - Intranasal immunization with LACK-DNA promotes protective immunity in hamsters
      challenged with Leishmania chagasi.
AB  - LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in
      protozoans of the genus Leishmania which is associated with the
      immunopathogenesis and susceptibility of BALB/c mice to L. major infection.
      Previously, we demonstrated that intranasal immunization with a plasmid carrying
      the LACK gene of Leishmania infantum (LACK-DNA) promotes protective immunity in
      BALB/c mice against Leishmania amazonensis and Leishmania chagasi. In the present
      study, we investigated the protective immunity achieved in hamsters intranasally
      vaccinated with 2 doses of LACK-DNA (30 MUg). Compared with controls (PBS and pCI
      neo plasmid), animals vaccinated with LACK-DNA showed significant reduction in
      parasite loads in the spleen and liver, increased lymphoproliferative response
      and increased nitric oxide (NO) production by parasite antigen-stimulated
      splenocytes. Furthermore, hamsters vaccinated with LACK-DNA presented high IgG
      and IgG2a serum levels when compared to control animals. Our results showed that
      intranasal vaccination with LACK-DNA promotes protective immune responses in
      hamsters and demonstrated the broad spectrum of intranasal LACK-DNA efficacy in
      different host species, confirming previous results in murine cutaneous and
      visceral leishmaniasis.

PMID- 21867592
TI  - Do shared etiological factors contribute to the relationship between sexual
      orientation and depression?
AB  - BACKGROUND: Gays, lesbians and bisexuals (i.e. non-heterosexuals) have been found
      to be at much greater risk for many psychiatric symptoms and disorders, including
      depression. This may be due in part to prejudice and discrimination experienced
      by non-heterosexuals, but studies controlling for minority stress, or performed
      in very socially liberal countries, suggest that other mechanisms must also play
      a role. Here we test the viability of common cause (shared genetic or
      environmental etiology) explanations of elevated depression rates in non
      heterosexuals. METHOD: A community-based sample of adult twins (n=9884
      individuals) completed surveys investigating the genetics of psychiatric
      disorder, and were also asked about their sexual orientation. Large subsets of
      the sample were asked about adverse childhood experiences such as sexual abuse,
      physical abuse and risky family environment, and also about number of older
      brothers, paternal and maternal age, and number of close friends. Data were
      analyzed using the classical twin design. RESULTS: Non-heterosexual males and
      females had higher rates of lifetime depression than their heterosexual
      counterparts. Genetic factors accounted for 31% and 44% of variation in sexual
      orientation and depression respectively. Bivariate analysis revealed that genetic
      factors accounted for a majority (60%) of the correlation between sexual
      orientation and depression. In addition, childhood sexual abuse and risky family
      environment were significant predictors of both sexual orientation and
      depression, further contributing to their correlation. CONCLUSIONS: Non
      heterosexual men and women had elevated rates of lifetime depression, partly due
      to shared etiological factors, although causality cannot be definitively
      resolved.

PMID- 21867593
TI  - Alcohol-use disorder severity predicts first-incidence of depressive disorders.
AB  - BACKGROUND: Previous studies suggest that alcohol-use disorder severity, defined
      by the number of criteria met, provides a more informative phenotype than
      dichotomized DSM-IV diagnostic measures of alcohol use disorders. Therefore, this
      study examined whether alcohol-use disorder severity predicted first-incident
      depressive disorders, an association that has never been found for the presence
      or absence of an alcohol use disorder in the general population. METHOD: In a
      national sample of persons who had never experienced a major depressive disorder
      (MDD), dysthymia, manic or hypomanic episode (n=27 571), we examined whether a
      version of DSM-5 alcohol-use disorder severity (a count of three abuse and all
      seven dependence criteria) linearly predicted first-incident depressive disorders
      (MDD or dysthymia) after 3-year follow-up. Wald tests were used to assess whether
      more complicated models defined the relationship more accurately. RESULTS: First
      incidence of depressive disorders varied across alcohol-use disorder severity and
      was 4.20% in persons meeting no alcohol-use disorder criteria versus 44.47% in
      persons meeting all 10 criteria. Alcohol-use disorder severity significantly
      predicted first-incidence of depressive disorders in a linear fashion (odds ratio
      1.14, 95% CI 1.06-1.22), even after adjustment for sociodemographics, smoking
      status and predisposing factors for depressive disorders, such as general
      vulnerability factors, psychiatric co-morbidity and subthreshold depressive
      disorders. This linear model explained the relationship just as well as more
      complicated models. CONCLUSIONS: Alcohol-use disorder severity was a significant
      linear predictor of first-incident depressive disorders after 3-year follow-up
      and may be useful in identifying a high-risk group for depressive disorders that
      could be targeted by prevention strategies.

PMID- 21867594
TI  - Construction of Ipr1 expression vector and development of cloned embryos in
      vitro.
AB  - The purpose of this study was to prepare intracellular pathogen resistance 1
      (Ipr1) transgenic donor cells for somatic cell nuclear transfer (SCNT). Based on
      our current understanding of Ipr1, a macrophage special expression vector pSP
      EGFP-Ipr1was constructed. Bovine fetal fibroblasts were transfected with pSP-EGFP
      Ipr1. The green fluorescent protein (GFP)-expressing cells were selected and
      transferred into enucleated bovine oocytes. Then, the rates of oocyte cleavage
      and blastocyst formation of transgenic cells and non-transgenic cells were
      observed, respectively. The results showed that reconstructed embryos derived
      from transgenic cells could successfully develop into blastocysts, most of which
      were GFP-positive. This study may provide cloned embryos for the production of
      anti-tuberculosis transgenic animals.

PMID- 21867595
TI  - Artificial oocyte activation and human failed-matured oocyte vitrification
      followed by in vitro maturation.
AB  - The investigation presented in this paper was conducted on the effect of oocytes
      activation on frozen-thawed human immature oocytes followed by in vitro
      maturation (IVM). A total of 386 failed-matured oocytes (germinal vesicle (GV)
      and metaphase I (MI) stages) was randomly divided into two groups: fresh group
      and vitrification group, GV group and MI group, respectively). The matured
      oocytes were subject to intracytoplasmic sperm injection (ICSI) after IVM had
      been carried out. The vitrification group was randomly divided into two groups:
      controlled and artificial oocyte activation (AOA). The injected oocytes in the
      controlled group were cultured in cleavage medium. The AOA group oocytes were
      activated by exposing them to 7% anhydrous alcohol for 6 min then cultured in
      cleavage medium as well. The rates of fertilization and early embryonic
      development were compared between the controlled and AOA groups. In MI
      vitrification group, the high-quality embryo formation rate and blastocyst
      formation rate were significantly higher in the AOA group than in the controlled
      group (P < 0.01). In the GV vitrification group, the high-quality embryo
      formation rate was significantly higher in the AOA group than in the controlled
      group (P < 0.05). These results indicate that AOA may be good for early embryonic
      development of vitrified immature human oocytes.

PMID- 21867596
TI  - Insights into the genetics of osteoporosis from recent genome-wide association
      studies.
AB  - Osteoporosis, which is characterised by reduced bone mineral density (BMD) and an
      increased risk of fragility fractures, is the result of a complex interaction
      between environmental factors and genetic variants that confer susceptibility.
      Heritability studies have shown that BMD and other osteoporosis-related traits
      such as ultrasound properties of bone, skeletal geometry and bone turnover have
      significant inheritable components. Although previous linkage and candidate gene
      studies have provided few replicated loci for osteoporosis, genome-wide
      association approaches have produced clear and reproducible findings. To date, 20
      genome-wide association studies (GWASs) for osteoporosis and related traits have
      been conducted, identifying dozens of genes. Further meta-analyses of GWAS data
      and deep resequencing of rare variants will uncover more novel susceptibility
      loci and ultimately provide possible therapeutic targets for fracture prevention.

PMID- 21867597
TI  - Advance care planning for people with dementia: a review.
AB  - BACKGROUND: Few people with dementia have made advance plans for their health
      care. Advance care planning (ACP) is a process of discussion between an
      individual and their care providers that takes account of wishes and preferences
      for future care. We aimed to examine the facilitators and inhibitors to ACP in
      people with dementia. We also aimed to identify key themes in the literature and
      critically review the methodologies used. METHODS: We systematically searched the
      English language literature including PubMed, CINAHL, AMED, PsychINFO, EMBASE and
      BNI. We included empirical studies which reported the characteristics of the
      patient population, the type of advance care planning used and the study setting,
      and which involved people with dementia, family members or professional carers.
      RESULTS: We identified 17 studies (11 quantitative methods, one qualitative and
      five mixed methods). We found one ACP intervention which changed outcomes for
      people with dementia. Key themes were identified: there is a point at which
      cognition decreases critically so that an advanced care plan can no longer be
      made; factors present in family carers and professionals can influence decision
      making and the ACP process; ACPs are affected by preferences for life sustaining
      treatments; ACP in dementia may differ from other illness groups; and there is a
      need for education relating to ACP. CONCLUSION: The current evidence base for ACP
      in dementia is limited. Since UK government policy recommends that all people
      should engage in ACP, more evidence is needed to understand the feasibility and
      acceptability of advanced care plans for people with dementia.

PMID- 21867598
TI  - Supplementation with the histone deacetylase inhibitor trichostatin A during in
      vitro culture of bovine embryos.
AB  - Trichostatin A (TSA) is a histone deacetylase inhibitor that induces histone
      hyperacetylation and increases gene expression levels. The aim of the present
      study was to establish a suitable condition for the use of TSA in in vitro
      cultures of bovine embryos, and to determine whether TSA would increase
      blastocyst rates by improvement of chromatin remodelling during embryonic genome
      activation and by increasing the expression of crucial genes during early
      development. To test this hypothesis, 8-cell embryos were exposed to four
      concentrations of TSA for different periods of time to establish adequate
      protocols. In a second experiment, three experimental groups were selected for
      the evaluation of embryo quality based on the following parameters: apoptosis,
      total cell number and blastocyst hatching. TSA promoted embryonic arrest and
      degeneration at concentrations of 15, 25 and 50 nM. All treated groups presented
      lower blastocyst rates. Exposure of embryos to 5 nM for 144 h and to 15 nM for 48
      h decreased blastocyst hatching. However, the terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay (TUNEL) assay revealed similar
      apoptosis rates and total cell numbers in all groups studied. Although, in the
      present study, TSA treatment did not improve the parameters studied, the results
      provided background information on TSA supplementation during in vitro culture of
      bovine embryos and showed that embryo quality was apparently not affected,
      despite a decrease in blastocyst rate after exposure to TSA.

PMID- 21867599
TI  - Effect of cryoprotectants on the survival of cascudo preto (Rhinelepis aspera)
      embryos stored at -8  degrees C.
AB  - Cryopreservation of germplasm provides a promising method to preserve fish
      genetic material, which is of great importance in preservation of species
      diversity, aquaculture, and management of fish models used in biomedical
      research. In the present study, cryopreservation of Rhinelepis aspera embryos, a
      Brazilian endangered species, was studied for the first time using a short-term
      cooling protocol. Embryos at blastoporous closing stage were selected, placed in
      6-ml glass vials and stored at -8  degrees C for 6 h in 10 different
      cryoprotectant solutions: S1 (17.1% sucrose + 9% methanol); S2 (17.1% sucrose +
      9% DMSO); S3 (8.5% sucrose + 8.5% glucose + 9% methanol); S4 (8.5% sucrose + 8.5%
      glucose + 9% DMSO); S5 (17.1% sucrose + 9% ethylene glycol); S6 (8.5% sucrose +
      8.5% glucose + 9% ethylene glycol); S7 (17.1% sucrose + 4.5% methanol + 4.5%
      DMSO); S8 (17.1% sucrose + 4.5% methanol + 4.5% ethylene glycol); S9 (17.1%
      sucrose + 4.5% DMSO + 4.5% ethylene glycol); and S10 (100% water). Embryo
      viability was assessed by hatching rate, counting live larvae and number of
      failed eggs under a stereomicroscope. The results showed that only the
      cryoprotectant solutions that contained methanol associated to sucrose (S1, S7
      and S8) provided partial protection of Rhinelepis aspera embryos from cold damage
      (over 50% hatching rate in S1), while the use of DMSO and ethylene glycol,
      isolated or in combination, resulted in no hatching rate. Further studies are
      needed in order to extend the storage time and to improve the hatching rate for
      the species.

PMID- 21867600
TI  - [Immune regulation role of A20 and its clinical significance].
AB  - A20 was originally identified as a TNFalpha-induced protein 3 (TNFAIP3), a key
      regulator of inflammation signalling pathways, as well as a NF-kappaB inhibitor.
      It plays a critical role in regulation of innate and adoptive immunity. Recently,
      A20 has also been proposed to function as a tumor suppressor. Lacking A20 gene is
      involved in inflammation-mediated autoimmune disease and tumorigenesis in several
      human B-cell lymphomas. Current advance concerning the feature of A20 expression
      in immune cells, the biological function, the immune regulated function in native
      immunity, humoral and cellular immunity, the inactivation of A20 in lymphocytic
      malignancies and the polymorphism and abnormal expression of A20 in autoimmune
      disease indicate that the clinical significance of A20 should be worthy to
      recognize and to be further employed in induction of immune tolerance, antitumor
      immuno-regulated therapy and antiviral immunotherapy and so on.

PMID- 21867601
TI  - [Na(+)/H(+) exchanger 1 expression and its effect on apoptosis in K562 and HL-60
      cells with DNA damage].
AB  - This study was aimed to investigate the expression of Na(+)/H(+) exchanger 1
      (NHE1) in K562 and HL-60 cells undergoing DNA damage induced by etoposide and to
      elucidate the regulating mechanism. Real-time quantitative PCR (RQ-PCR) and
      Western blot methods were used to determine the expression of NHE1 in K562 cells
      after the treating with etoposide. Meanwhile, the flow cytometry was used to
      detect the apoptosis of leukemic cells. The luciferase reporter vector containing
      NHE1 promoter was constructed to measure relative luciferase activity after
      treating with different etoposide concentrations. The results showed that the
      mRNA and protein of NHE1 increased in accordance with apoptosis ratio in HL-60
      cells after treated with etoposide (p < 0.05), but no such obvious increase in
      K562 cells. Treatment with NHE1 specific inhibitor could block etoposide induced
      alkalization and reduce the apoptosis ratio of HL-60 cells. The expression
      pattern and apoptosis alteration was not similar in K562 cells. Relative
      luciferase activity of reporter vector containing NHE1 promoter however increased
      in K562 cells after treated with etoposide. It is concluded that the expression
      of NHE1 is up-regulated in the process of apoptosis of HL-60 cells induced by
      etoposide and depends on the pHi increasing caused by NHE1 up-regulation which is
      not found in K562 cells although the transcriptional activity increased.

PMID- 21867602
TI  - [Influence of siRNA interfering beta-catenin on tumorigenicity in vivo of K562
      cell line].
AB  - The aim of this study was to investigate the effects of beta-catenin on the
      tumorigenicity of K562 cells in vivo. The beta-catenin expression in K562 cells
      was down-regulated through sequence-specific siRNA, and the treated K562 cells
      were implanted into BALB/c nude mouse subcutaneously. And the tumor-forming rate
      and tumor-forming curve (interference group) were observed. Experiments were
      divided into 3 group: interference group (implanted K562 cells transfected with
      beta-catenin interfering plasmid DNA), control group (implanted K562 cells
      transfected with unrelated sequence plasmid DNA) and untreated group (implanted
      K562 cells transfected without plasmid DNA). The results indicated that the tumor
      forming rates of untreated group (n = 9), control group (n = 8) and interference
      group (n = 9) were 100%, 87.5% and 0% respectively. The tumor-forming rate of
      interference group was significantly lower than those of the other 2 groups (p <
      0.001). Comparison of the tumor-forming curve between 3 groups, showed that in
      first 2 groups existed tumor-forming and their final tumor volumes were almost
      the same, but the tumor growth of untreated group was faster than that in control
      group; while in the interference group there was not tumor-forming. It is
      concluded that the beta-catenin expression level in K562 cells is down-regulated
      through the interference of sequence-specific siRNA, thus affecting their tumor
      forming potential in vivo.

PMID- 21867603
TI  - [Influence of BCR-ABL inhibitor STI571 on SARI expression in K562 cells].
AB  - In order to investigate the molecular mechanisms of SARI expression regulation in
      chronic myeloid leukemia (CML), 46 patients with CML and 40 healthy volunteers
      were recruited in this study. SARI expression in the peripheral blood mononuclear
      cells (PBMNC) of CML patients and healthy volunteers was assayed by using real
      time quantitative PCR. K562 cells were in vitro incubated with the BCR-ABL
      inhibitor STI571 (imatinib) at 37 degrees C and 5% CO2 for 24 hours, then SARI
      expression was detected by using real-time quantitative PCR. All experiments were
      repeated three times. The results showed that as compared with healthy
      volunteers, the expression of SARI mRNA in PBMNC of CML patients presented a
      lower level (p < 0.001). After exposure of K562 cells to STI571 (2.5 umol/L) for
      24 hours, the SARI expression was higher than that in K562 cells treated without
      STI571 (p < 0.001). It is concluded that the suppression of SARI expression is
      involved in CML pathogenesis, and BCR-ABL mediates the down-regulation of SARI
      mRNA expression in K562 cells. These findings suggest a new orientation for gene
      therapy in CML patients.

PMID- 21867604
TI  - [Comparison of protein expression profiles between bortezomib-resistant JurkatB
      cells with PSMB5 mutation and their parent cells].
AB  - This study was purposed to investigate the differences of cyto biological
      characteristics and protein expression levels between bortezomib-resistant T
      lymphoblastic lymphoma/leukemia cell lines JurkatB containing PSMB5 G322A
      mutation and their parent cell line Jurkat, The cytotoxicities of bortezomib and
      chemotherapeutic drugs to JurkatB5 cells (end selection concentration of
      bortezomib was 500 nmol/L), JurkatB8 (end selection concentration 800 nmol/L) and
      Jurkat cells were analyzed. The cell growth curves were drawn with viable cell
      counts by trypan blue assay, the colony formation rate were assayed by soft-agar
      colony culture, and the cell distributions in cell cycle were analyzed by flow
      cytometry, mRNA expression levels of multidrug resistance (MDR) genes MDR1, LRP
      and MRP were measured by real-time fluorescence quantitative RT-PCR, the
      differences of protein expression levels were detected by SpringBio antibody
      microarray containing 720 proteins. The results showed that the drug resistance
      multiples for 48 hours of JurkatB5 and JurkatB8 cells (relative to Jurkat) to
      bortezomib were increased by 33.52 and 39.04 times, respectively. JurkatB5 and
      JurkatB8 cells did not display significant cross-resistance to daunorubicin,
      adriamycin, vindesine, and etoposide after exposure for 48 hours. There were no
      significant differences in the cell growth curve, colony formation rate and cell
      distributions in cell cycle between JurkatB5, JurkatB8 and Jurkat cells (p >
      0.05). There were no significant differences of mRNA expression levels of MDR1,
      LRP, MRP between JurkatB5 and Jurkat cells (p > 0.05). There were 264 analyzable
      expression points detected by antibody microarray. Among them, 252 protein
      expression levels were not significantly different between JurkatB5, JurkatB8 and
      Jurkat cells (< 2-fold), including 15 drug resistance-related proteins. 12
      proteins were detected at higher or lower expression levels in JurkatB5 or
      JurkatB8 cells then that in Jurkat cells (cell division cycle protein 34, cell
      division cycle protein 37, CD34 Type II, matrix metalloproteinase-2, tenascin,
      Golgi complex, involucrin, histone deacetylase 1, perforin, prolactin, retinoic
      acid receptor beta, integrin beta-1), but no proteins were detected in JurkatB5
      and JurkatB8 cells with higher or lower expression levels than that in Jurkat
      cells. It is concluded that there are no significant differences in the
      characteristics of cellular biology between Jurkat and JurkatB with bortezomib
      resistant and PSMB5 G322A mutation. There are no significant phenotype change of
      MDR and overexpression of genes related to MDR in PSMB5 mutated cells. There are
      no significantly differential expressions of a majority of known proteins related
      to drug resistance, tumor cells growth, proliferation, apoptosis, malignancy
      degree, aggressiveness.

PMID- 21867605
TI  - [Expression pattern of myeloid differentiation-related transcription factor mRNA
      in differentiation of NB4 and HL-60 cells induced by all-trans retinoic acid].
AB  - Hematopoiesis is coordinated by a complex regulatory network of transcription
      factors that involves proliferation, differentiation and maturation of a very
      small population of pluripotent hematopoietic stem cells with self-renewing and
      differentiating into various specialized and distinct blood cell types.
      Malfunction of transcription factors may lead to diseases such as acute myeloid
      leukemia (AML). The purpose of this study was to investigate the expression
      pattern of transcription factor mRNA in acute myeloid leukemia (AML) cells during
      in vitro differentiation. The 2 human leukemic cell lines HL-60 and NB4 had been
      used as model cell lines. Differentiation of HL-60 and NB4 cells was induced by
      all-trans retinoic acid (ATRA) for 4 days. Morphological changes were observed by
      May-Grunwald Giemsa stainings, the CD11b expression level was detected by flow
      cytometry. Transcription factor mRNA profiles (PU.1, C/EBPalpha, epsilon, gamma,
      GATA-1, GATA-2) were determined by real time RT-PCR during in vitro HL-60 and NB4
      differentiation; The expression level of transcription factor mRNA was relatively
      quantitatively analyzed by using 2(-DeltaDeltaCT) and compared with control
      group. The results showed that the expression levels of PU.1 and C/EBP epsilon
      mRNA in NB4 differentiation group were 5.75 and 6.16, respectively, which were
      significantly higher than those in untreated group; while the expression level of
      C/EBPalpha, gamma, GATA-1, GATA-2 mRNA in NB4 differentiation group were 62%,
      31%, 63% and 8.7% respectively, which were significantly lower than those in
      untreated group; In HL-60 differentiation group, the expression levels of PU.1,
      C/EBPalpha, epsilon were 1.97, 1.95 and 2.35 respectively, which were
      significantly higher than those in untreated group; while the expression levels
      of C/EBPgamma, GATA-1, GATA-2 in HL-60 differentiation group were 20%, 21% and
      18% respectively, which were significantly lower than those in untreated group.
      It is concluded that dysregulation of transcription factors is a key contributing
      factor in the pathogenesis of acute myeloid leukemia.

PMID- 21867606
TI  - [Apoptosis-inducing effect of C-MYC siRNA on acute lymphoblastic leukemia Jurkat
      cell line].
AB  - The study was purposed to investigate the effects of C-MYC siRNA on the
      proliferation and apoptosis of acute lymphoblastic Jurkat cell line. siRNA
      targeting the site 1545-1565 of C-MYC mRNA was designed and chemically
      synthesized, then C-MYC siRNA was transfected into Jurkat cells by the transfer
      agent (HiPerFect Transfection Reagent), the morphological changes were observed
      under inverted microscope; the tetrazole compound (MTS) was applied to draw the
      cell growth curve; the cell colony test was used to detect the effect of C-MYC
      siRNA on the proliferation of Jurkat cells; the flow cytometry and TUNEL method
      were used to analyze the apoptosis of Jurkat cells. The results showed that after
      Jurkat cells were treated with different concentrations of C-MYC siRNA, the
      growth of Jurkat cells was inhibited to various degrees, inhibitory rate was
      enhanced as C-MYC siRNA concentration increased. C-MYC siRNA also could obviously
      inhibit the cell clony formation. The apoptosis of cells could be detected by
      flow cytometry and TUNEL method, the apoptosis rate of cells increased along with
      prolonging of treatment with C-MYC siRNA. It is concluded that the chemically
      synthesized C-MYC siRNA can inhibit significantly the proliferation and induce
      the apoptosis of Jurkat cells.

PMID- 21867607
TI  - [Effects of quercetin on multidrug resistance and expression of related genes in
      human erythroleukemic K562/a cells].
AB  - The study was aimed to investigate the effect of quercetin, flavonoid molecules
      on reversing leukemia multidrug resistance and its mechanism. K562/A cells were
      cultured in vitro with different concentrations of quercetin. Cell growth
      inhibition and adriamycin (ADR) sensitivity were detected by MTT method.
      Intracellular ADR concentration was determined by flow cytometry. Cell apoptosis
      was assayed by Annexin V/PI staining method. The expressions of drug transporter
      and apoptosis related genes were measured by real-time PCR array. The results
      indicated that quercetin inhibited the proliferation of K562 and K562/A in 5-160
      umol/L and with dose-dependent manner. Quercetin increased the sensitivity of
      K562/A cells to ADR in a low toxicity concentration. Flow cytometry showed that
      the quercetin increased the accumulation of ADR in K562/A cells when cells were
      co-cultured with 5 umol/L ADR for 2 hours. Quercetin could induce the apoptosis
      of K562 and K562/A cells with dose dependent manner. Furthermore, some drug
      transport related genes such as ATP-binding cassette (ABC) and solute carrier
      (SLC) and some apoptosis-related genes such as BCL-2, tumor necrosis factor
      (TNF), tumor necrosis factor receptor (TNFR) families were down-regulated by
      quercetin. It is concluded that quercetin reverses MDR of leukemic cells by
      multiple mechanisms and the reversing effect is positively related to drug
      concentration.

PMID- 21867608
TI  - [Proteasome inhibitor bortezomib inducing apoptosis of K562 cells not affected by
      bone marrow mesenchymal stem cells in vitro].
AB  - The study was aimed to investigate the effects of proteasome inhibitor bortezomib
      on the apoptosis of K562 cells in the presence of bone marrow mesenchymal stem
      cells, and explore its effect on expression of adhesion molecule VCAM-1 of both
      MSC and K562 cells. The K562 cells were co-cultured in direct contact with MSC,
      while the control cells were just cultured alone. Bortezomib was administered at
      a final concentration of 50 nmol/L. Cell apoptosis was assayed by flow cytometry
      with Annexin-V/PI double staining kit. The VCAM-1 gene expression was determined
      by reverse transcription polymerase chain reaction (RT-PCR). The results
      indicated that bortezomib could induce apoptosis of K562 cells in a time
      dependent manner. K562 cells growing on the layer of MSC demonstrated the similar
      sensitivity to apoptosis induction of bortezomib. K562 cells which did not
      express VCAM-1 originally were induced to express VCAM-1 mRNA when co-cultured
      with MSC. This effect could be abrogated by bortezomib treatment. Furthermore,
      bortezomib significantly downregulated the VCAM-1 expression of MSC. It is
      concluded that the proteasome inhibitor bortezomib can induce apoptosis of K562
      cells even though in presence of the MSC layer.

PMID- 21867609
TI  - [Effects of Clostridium difficile toxin a on proliferation of K562 cells].
AB  - This study was aimed to investigate the effect of clostridium difficile toxin A
      (Tcd A) on proliferation of K562 cells and its mechanism. The proliferative
      activity of K562 cells exposed to Tcd A was tested by MTT assay; cell cycle
      distribution and mitochondrial membrane potential were analyzed by flow
      cytometry; the protein expression of cytochrome C and DNA fragmentation were
      observed by immunohistochemistry staining and agarose gel electrophoresis
      respectively. The results indicated that Tcd A inhibited proliferation of K562
      cells in a time-and concentration-dependent manner. Cells were arrested at
      G(0)/G(1) phase. Peak of apoptosis appeared. The protein expression of cytochrome
      C increased as compared with control group (p < 0.05). Agarose gel
      electrophoresis of DNA from K562 treated with Tcd A revealed a "ladder" pattern.
      It is concluded that clostridium difficile toxin A can inhibit proliferation and
      induce apoptosis of K562 cells. The mechanism may be in relation to decrease of
      mitochondrial membrane potential and the release of cytochrome C from
      mitochondria matrix.

PMID- 21867610
TI  - [Effects of bortezomib alone or combined with arsenic trioxide on the apoptosis
      of Jurkat cells and expression of livin mRNA].
AB  - This study was aimed to investigate the effect of bortezomib alone or combined
      with arsenic trioxide on the apoptosis of Jurkat cells and expression of livin
      mRNA. The Jurkat cells were cultured and treated with different concentrations of
      bortezomib, arsenic trioxide or their combination for 24 hours. Then, the
      expression of livin mRNA was detected by RT-PCR, the cell proliferation was
      analyzed with MTT assay and flow cytometry. The results showed that 5 - 25 nmol/L
      bortezomib could effectively inhibit Jurkat cells in a dose-dependent manner, the
      group of bortezomib combined with arsenic trioxide showed more inhibitory effect
      on Jurkat cells than the effect of bortezomib alone or arsenic trioxide alone on
      Jurkat cells. The expression of livin mRNA in Jurkat cells decreased in a dose
      dependent manner after treated with bortezomib, which was downregulated
      significantly after combined treatment. It is concluded that bortezomib and
      arsenic trioxide can induce apoptosis by inhibiting the expression of livin mRNA
      in Jurkat cells. The combination of bortezomib with arsenic trioxide displays a
      synergistic effect.

PMID- 21867611
TI  - [Isocitrate dehydrogenase gene mutations in acute myeloid leukemia].
AB  - The purpose of this study was to identify point mutation of the isocitrate
      dehydrogenase gene (IDH1 and IDH2) in patients with acute myeloid leukemia(AML)
      and its clinical significance. 90 de novo AML patients were selected for this
      study, the genomic DNA was served as template, the exon4 of IDH1 and IDH2 were
      amplified respectively. The IDH mutation was detected by using directly
      sequencing method for PCR product. The results indicated that among 90 de novo
      AML patients, 4 patients (4.4%) showed the IDH1 gene mutation positive, and
      7(7.8%) patients showed IDH2 gene mutation positive. None was found harboring
      both mutations, the overall rate of mutation positive of them was 12.2%. In the
      AML patients with IDH gene mutation positive, the rate of normal karyotype was
      72.7%, which was significantly higher than that in abnormality karyotype. The CR
      rate in mutation positive patients was 72.7%, which seemed as if higher than that
      in mutation negative patients, but without statistical significance. The mutation
      disappeared when the patients gained CR, and reappeared in same loci after
      relapse occurred. It is concluded that the IDH gene point mutation appears in
      normal karyotype patients, especially in patients combined with NPM1 gene
      mutation. The IDH gene mutation may be an important target for therapy and
      evaluating clinical prognosis of patients with normal karyotype.

PMID- 21867612
TI  - [Analysis of IKAROS6 expression in 73 patients with chronic myelogenous
      leukemia].
AB  - This study was aimed to evaluate IKAROS6 expression in patients with chronic
      myelogenous leukemia (CML) and its clinical significance. cDNAs from 73 CML
      patients were amplified by PCR and sequenced for IKAROS expression to elucidate
      clinical characteristics in IKAROS6 positive patients. The results showed that
      there was no IKAROS6 gene expression in 8 healthy controls and 15 CML patients in
      chronic phase and accelerated phase, and 15 cases (35.71%) were IKAROS6 positive
      in lymphoblast crisis samples among 42 newly diagnosed CML; however, none was
      found in myeloblast crisis of 16 newly diagnosed CML. Among 42 lymphoblast crisis
      of CML, the complete remission (CR) rate of IKAROS6 expression positive patients
      reached 40% (6/15), which was obviously lower than that in IKAROS6 negative
      patients (85.19%, 23/27) (p < 0.01), IKAROS6 positive patients relapsed after CR
      for 15 (2 - 18) months with relapse rate 66.7% (4/6), which was higher than that
      in expressed wild type IKAROS gene patients (21.74%, 5/23) (p < 0.05). It is
      concluded that abnormal expression of IKAROS gene dominated by IKAROS6 isoforms
      can be detected in lymphoblast crisis samples of CML patients. Abnormal
      expression of IKAROS gene may be an important factor in lymphoblast crisis of
      CML. Therefore, detection of IKAROS gene expression may be important for target
      therapy and evaluation of clinical prognosis of CML patients.

PMID- 21867613
TI  - [Cyclin D1, hTERT expression and telomerase activity in HL-60 and HL-60A cell
      lines and their significance].
AB  - To observe the expression of cyclin D1, hTERT, and telomerase activity in MNC, HL
      60, HL-60A and to explore their effects on leukemogenesis and drug-resistance,
      normal human peripheral blood mononuclear cells, HL-60 cells sensitive to
      adriamycin and HL-60A cells resistant to adriamycin were investigated. The cell
      cycle was analyzed by flow cytometry, and the apoptosis was analyzed by Annexin V
      FITC(+) PI staining. Expressions of cyclin D1 and hTERT were determined by real
      time PCR and Western blot. Telomerase activity was detected by TRAP-ELISA. The
      results indicated that the percentage of MNC, HL-60 and HL-60A in S phase was
      (10.21 + 2.11)%, (44.93 + 3.00)%, and (51.38 + 1.10)% respectively; the
      percentage of apoptosis cells was (16.14 + 2.13)%, (7.53 + 0.92)%, (4.15 + 0.96)%
      respectively; the expression of mRNA and protein for cyclin D1 and hTERT
      increased; the telomerase activities of HL-60 and HL-60A were higher (p = 0.000),
      whereas the difference between HL-60 and HL-60A was no statistically significant
      (p = 0.232); positive correlation between cyclin D1, hTERT and telomerase
      activity had been found (p < 0.01). It is concluded that the cells of S phase
      increased while the apoptotic cells decreased in HL-60 and HL-60A, especially in
      HL-60A, which may be due to the up-regulation of cyclin D1, hTERT and telomerase
      activity.

PMID- 21867614
TI  - [JAK2V617F mutation in the patients with myeloproliferative disorder and its
      relation with clinical characteristics].
AB  - This study was aimed to investigate the incidence of JAK2V617F mutation in BCR
      ABL negative patients with myeloproliferative disorders (MPD) and its relation
      with clinical characteristics of MPD. The sensitive and specific test for
      JAK2V617F mutation was established for improving diagnosis level in Gansu
      province. 47 BCR/ABL negative MPD patients and 12 healthy people were enrolled in
      this study. Allele specific polymerase chain reaction (AS-PCR) was used to
      amplify the exon 12 of JAK2 gene which harbours V617F mutation. The PCR products
      were identified by DNA sequencing. And its relation with clinical characteristics
      of MPD was analyzed also. The results indicated that the incidence of JAK2V617F
      positive mutation in 47 patients with BCR-ABL negative MPD was 74.5 % (35/47),
      including 83.9 %(26/31) in patients with polycythemia vera (PV), 60 % (9/15) in
      patients with essential thrombocythemia (ET), only in one patient with idiopathic
      myelofibrosis (IMF). In PV group, the patients with JAK2V617F positive mutation
      had higher counts of WBC and Plt than patients with JAK2V617F negative mutation.
      In ET group, the patients with JAK2V617F positive mutation had higher WBC count
      and Hb level than those in the patients with JAK2V617F negative mutation with
      tendency of suffering from complications such as hepatosplenomegaly, haemorrhage
      and thrombosis. It is concluded that JAK2V617F mutation is more frequent in BCR
      ABL negative patients with MPD, the AS-PCR method is sensitive and specific for
      detection of the mutation and may successfully use in clinical examination.

PMID- 21867615
TI  - [Gene expression of livin and survivin in adult patients with acute lymphoblastic
      leukemia and its clinical significance].
AB  - This study was aimed to investigate the expressions of livin and survivin in
      adult patients with acute lymphoblastic leukemia (ALL) and clinical significance.
      The expressions of livin and survivin mRNA in bone marrow mononuclear cells of 95
      adult ALL patients including 52 de novo patients, 23 relapsed patients and 20
      patients with complete remission (CR), and 20 healthy adults as normal controls
      were detected by using RT-PCR. The results indicated that the expression of livin
      and survivin mRNA in de novo and relapsed patients was higher than that in normal
      controls and patients with CR. There were no significant relation of expression
      level with clinical features such as age, sex, type and de novo leukocyte level.
      The CR rate in de novo adult ALL patients with positive expression of livin and
      survivin was lower than that in adult ALL patients with negative gene expression.
      No relation of mRNA expression between livin and survivin was found in de novo
      adult ALL patients. It is concluded that genes livin and survivin may be involved
      in the pathogenesis and progression of adult ALL. Overexpression of livin or
      survivin may show poor progression. There is no relation of expression between
      genes livin and survivin in de novo adult ALL patients.

PMID- 21867616
TI  - [Expression of osteopontin and VEGF in acute leukemia and their relationship with
      angiogenesis].
AB  - The aim of this study was to investigate the expression of osteopontin (OPN) and
      vascular endothelial growth factor (VEGF) in acute leukemia (AL) and its
      significance in the angiogenesis and progress of AL. Serum levels of OPN and VEGF
      in 25 de novo patients, 19 complete remitted (CR) patients, 14 unremitted
      patients, and 11 relapsed patients with AL were measured by enzyme-linked
      immunosorbent assay (ELISA), and compared with those in normal controls. The
      results showed that the serum levels of OPN and VEGF in de novo, unremitted,
      relapsed patients were significantly higher than those in normal controls and CR
      patients (p < 0.01). Compared with de novo AL patients group, the serum levels of
      OPN and VEGF in CR patients decreased significantly, but showed no significant
      difference from those in normal controls (p > 0.05). The expression of OPN and
      VEGF in acute leukemia was positively correlated with occurrence and development
      of AL. It is concluded that the expressions of OPN and VEGF are closely related
      with AL occurrence and development, the OPN may regulate VEGF expression and
      promote angiogenesis in acute leukemia. Preventing expressions of OPN may seem as
      targets for leukemia therapy in the future.

PMID- 21867617
TI  - [Primary study on origination of bone marrow abnormal clones in patients with
      myelodysplastic syndrome].
AB  - The study was aimed to investigate the origination of abnormal clones in
      hematopoietic cells of MDS patients. That is to say if there are abnormal clones
      in CD34(+)CD38(-) and CD34(+)CD38(+) cells and their proportions in MDS patients.
      Immuno-magnetic bead technique was used to sort CD34(+)CD38(-) and CD34(+)CD38(+)
      in bone marrow mononuclear cells of 9 MDS patients with chromosome abnormalities
      (four cases with trisomy 8, 1 case with trisomy 8 complex karyotype, 2 cases with
      5q(-), 1 case with 5q(-)complex karyotype, 1 case with 5q(-) accompanying trisomy
      8) and smears were made respectively. Then the percentage of abnormal clones in
      CD34(+)CD38(-) and CD34(+)CD38(+) cells were compared by using FISH. The results
      indicated that abnormal clones were involved in the two population cells in 9
      patients. The percentage of abnormal clones in CD34(+)CD38(-) cells (41.8 +/-
      8.4%)was obviously lower than that in CD34(+)CD38(+) cells(72.4 +/- 7.7%) (p <
      0.001), and the percentage of abnormal clones in karyocytes was 70.8 +/- 9.2%. It
      is concluded the abnormal clones of bone marrow hematopoietic cells may originate
      from stem cell stage in MDS patients with 5q(-) and +8, and the abnormal clones
      are predominant at stage of progenitors.

PMID- 21867618
TI  - [Ki-67 proliferative index in non-Hodgkin's lymphoma and its clinical
      significance].
AB  - This study was aimed to investigate the relationship of Ki-67 proliferation index
      (Ki-67 PI) with non-Hodgkin's lymphoma(NHL) typing and biological behavior, as
      well as its significance in clinical characters and prognosis of diffuse large B
      cell lymphoma(DLBCL). A total of 542 cases of NHL in our hospital from 1st
      January 2001 to 31st December 2010 were retrospectively analyzed, and Ki-67 PI
      was all assayed immunohistochemically, and a total of 82 cases of newly-diagnosed
      DLBCL with more clinical records were investigated. The results indicated that
      according to the World Health Organization (WHO) histopathological classification
      of lymphoma, Ki-67 PI was different as classification for NHL subgroups was
      different. The Ki-67 PI increased with aggressive progression of NHL. The mean Ki
      67 PI ranged from 25.5% in indolent lymphoma to 98.4% in very aggressive
      lymphoma. ROC curve analysis demonstrated that the 50% was the cut-off value
      distinguishing indolent from aggressive disease. On ROC curve analysis, Ki-67 PI
      of 75% was found to significantly discriminate patients with DLBCL who had a good
      or bad prognosis. There was a significant correlation of Ki-67 PI with Ann Arbor
      stage and LDH level. When the DLBCL cases were divided by Ann Arbor stage and IPI
      score, the 3-year overall survival (OS) of patients with a low Ki-67 PI (<= 75%)
      in the group of Ann Arbor stage III-IV and high LDH level was higher than those
      with a high Ki-67 PI (> 75%) among the patients with B symptoms and IPI 3.0-5. 3
      year OS in those with a low Ki-67 PI (<= 75%) in the group of Ann Arbor stage III
      IV and normal LDH level was higher than those with a high Ki-67 PI (> 75%) among
      the patients with B symptoms. 3-year OS of patients with a low Ki-67 PI (<= 75%)
      in the group at III-IV stage and a high LDH level was higher than those with a
      high Ki-67 PI (> 75%). It is concluded that a cut-off value of 50% can be helpful
      to differentiate indolent from aggressive NHL. In DLBCL, a cut-off value of 75%
      can distinguish patients with a good or bad prognosis when combined with other
      prognostic factors, i.e. B symptoms, Ann Arbor stage, IPI score and lactate
      dehydrogenase (LDH) level.

PMID- 21867619
TI  - [Inhibitory effect of phenylhexyl isothiocyanate on notch signaling of multiple
      myeloma cells in vitro].
AB  - In order to investigate the mechanisms of phenylhexyl isothiocyanate (PHI)
      inhibiting the proliferation of multiple myeloma cell RPMI8226 in vitro, the
      RPMI8226 cells were co-cultured with PHI of various concentrations. The
      inhibition of proliferation was measured by MTT test and the cell apoptosis was
      assayed by DAPI staining. The changes of Notch1, Jagged2, BCL-2 and p-Akt
      proteins in the PHI-treated cells were detected by Western blot. The results
      showed that PHI inhibited RPMI8226 cell proliferation in certain concentration
      range and induced their apoptosis. The inhibiting effect caused by PHI showed a
      concentration-and time-dependent manner. The PHI decreased expressions of Notch1
      and Jagged2 proteins in a concentration-and time-dependent manners, the levels of
      BCL-2 and p-Akt declined at the same time. It is concluded that PHI can inhibit
      proliferation of RPMI8226 cells, and induce their apoptosis. The cell apoptosis
      is associated with the inhibition of Notch signaling and downstream targets BCL-2
      and p-Akt proteins of RPMI8226 cells, PHI may be a new Notch signaling inhibitor
      and a promising therapeutic drug for multiple myeloma.

PMID- 21867620
TI  - [Effects of decitabine on biological behavior of U266 cells].
AB  - This study was aimed to explore the effects of decitabine on the biological
      behaviour of U266 cells in vitro so as to provide a new thinking and experiment
      basis, as well as new evidences for the pathogenesis of multiple myeloma. MTT and
      colony formation assays were used to evaluate the impact of decitabine on the
      ability of proliferation of U266 cells; flow cytometry was used to analyze the
      cell distribution in cell cycle; transwell chamber and matrigel assays were used
      to observe the ability of migration and invasion. The results indicated that
      decitabine could significantly suppress the proliferation of U266 cells in time
      and dose-dependent manners. The flow cytometric analysis demonstrated that the
      cells in G(0)-G(1) phase significantly increased while the cells in S and G(2)/M
      phase decreased. The migration and matrigel invading tests showed that the number
      of cells moving into under chamber of transwell decreased after U266 cells
      treated with decitabine. It is concluded that decitabine may act as an effective
      drug for MM by inhibiting the proliferation, migration and invasion ability, and
      the specific mechanism needs to be deeply explored.

PMID- 21867621
TI  - [Efficacy, side effects and blood concentration monitoring of high-dose
      methotrexate in treatment of 180 children with acute lymphoblastic leukemia].
AB  - This study was purposed to investigate the effects of high-dose methotrexate (HD
      MTX)-CF + VDT protocol on pediatric acute lymphoblastic leukemia (ALL) by means
      of retrospective analysis. MTX plasma concentration was dynamically detected and
      evaluated so as to avoid or reduce the side effects of HD-MTX, and adjust the
      time and dosage of calcium folinate (CF) or carry out the plasma exchange as
      occasion requires. Totally 180 cases of ALL were enrolled in this study, and
      received 380 administration of HD-MTX-CF + VDT protocol, including 122 patients
      with induction therapy as well as 58 cases during maintenance therapy, among
      which 68 cases were defined as low risk, 80 cases as middle risk and 32 cases as
      high risk. 2.0 g/m(2) MTX, 3.0 g/m(2) MTX, and 5.0 g/m(2) MTX were individually
      used according to low risk, middle risk or T immunohistochemical expression. The
      results indicated that 36.3% cases showed the side-effects of HD-MTX including
      mucocutaneous lesions, gastrointestinal reaction, hepatic dysfunction, renal
      damage, fever, myelosuppression, cardiotoxicity, infection and allergic response.
      All of these side effects were reversible through treatment. The elimination
      delay of MTX occurred in 110 cases, out of which 3 cases got MTX concentration >
      10 umol/L at 24 hours, 50 cases > 1.0 umol/L at 44 hours, the remaining 57 cases
      > 0.1 umol/L at 68 hours. CF dosage was adjusted according to the concentration
      of MTX until it was less than 0.1 umol/L. 1 case had renal interstitial
      inflammation and acute renal failure, but finally he was cured. No patients
      received plasma exchange or died. It is concluded that the extramedullary
      leukemia control protocol, in which MTX is main drug, is effective therapy for
      obtaining long-term remission and event-free survival rate in ALL patients, but
      the side effects and risks increase along with the increase of MTX dose. The
      metabolic level of HD-MTX has found to be obvious individual, so the dynamic
      monitoring of MTX concentration in plasma and administration of proper dosage of
      CF are important factors for HD-MTX protocol application in ALL patients.

PMID- 21867622
TI  - [Clinicopathological features of acute tumor lysis syndrome in elderly patients
      with malignant non-Hodgkin's lymphoma].
AB  - This study was purposed to investigate the clinicopathological features of acute
      tumor lysis syndrome (ATLS) in elderly patients with malignant non-Hodgkin's
      lymphoma, so as to explore its diagnosis and treatments. 2 cases of ATLS in
      elderly patients with non-Hodgkin's lymphoma were retrospectively analyzed,
      including progress of tumor, the level of laboratory examination, clinical
      manifestation and response to treatments. Data regarding clinical and biochemical
      parameters were collected. The results indicated that the 2 patients with non
      Hodgkin's lymphoma were found to have high tumor burden, and were sensitive to
      anti-tumor treatments, and had many promoting factors of ATLS. 1 patient
      displayed hyperkalemia, but another displayed hypokalemia. Both patients were
      given allopurinol, hydration and alkalization, and one was given dialysis. But
      both died because of disease deterioration. ATLS rarely occurred in patients who
      were treated by rituximab only. But the patients with high grade NHL and high
      tumor burden maybe develop ATLS during 1 - 4 days after given rituximab. In
      conclusion, ATLS is one of factors of death in patients with malignant lymphoma.
      The clinical manifestation is not typical, and the diagnosis mainly depends on
      laboratory examination parameters. Earlier judgment, prophylaxis and effective
      treatment are important for improving prognosis of elderly DLBCL-NHL.

PMID- 21867623
TI  - [Detection of WT1 gene in acute myeloid leukemia children by real-time
      fluorescent quantitative RT-PCR and its clinical significance].
AB  - Objective of this study was to establish a SYBR Green Ireal-time reverse
      transcription-polymerase chain reaction (RT-PCR) for quantitative detection of
      WT1 gene mRNA in children with acute myeloid leukemia (AML) and investigate its
      clinical significance. SYBR Green Ireal-time RT-PCR was used to quantitatively
      detect the mRNA expression of WT1 gene in 30 newly diagnosed AML patients, 12
      cases of remission (30), 18 relapsed patients and 30 cases of normal bone marrow
      cell morphology, and dynamically to detect the expression of WT1 gene in 20 newly
      diagnosed AML children. ABL served as internal reference gene, and the 2(
      DeltaDeltact) method was used to calculate the relative expression. The results
      showed that (1) the expression of WT1 gene in newly diagnosed AML children was
      higher than that of the normal controls and the patients with remission (p <
      0.001); there were no significant difference of WT1 gene expression between AML
      patients with remission and normal controls (p > 0.05), which were same as in
      relapsed patients and newly diagnosed patients (p > 0.05); (2) WT1 gene in 20
      newly diagnosed AML children highly expressed before the children were initially
      treated, decreased when they were complete remission, then expression increased
      again when their AML relapsed. The WT1 gene expression level began to rise in 5
      cases before clinical relapse at 5 - 7 months; (3) the complete remission rate
      (CR) and 3 year overall survival (OS) did not show significant difference between
      the WT1-positive group and negative group when dynamically monitoring WT1 gene
      expression of 20 newly diagnosed children with AML. 3-year OS of WT1-positive
      group at the 22 - 30 days after initial treatment was significantly lower than
      that of the negative group (p < 0.05). It is concluded that SYBR Green Ireal-time
      RT-PCR is a rapid, efficient, sensitive and specific method. WT1 gene in AML
      childhood plays a role of cancer-promoting. The change of WT1 gene expression
      level contributes to evaluate the therapeutic efficacy, detect the minimal
      residual diseases and analyze the prognosis.

PMID- 21867624
TI  - [Effects of TSP2-8 and CUB1+2 domains on secretion direction of von Willebrand
      factor-cleaving protease].
AB  - This study was aimed to explore if the intracellular transportation direction of
      von Willebrand factor-cleaving protease (ADAMTS13, vWF-CP) after synthesis is
      determined by the carboxyl terminal TSP2-8CUB1+2 domains of ADAMTS13 and to
      decipher the relationship between the structure and function of ADAMTS13. The
      recombinant plasmids pcDNA3.1-ADAMTS13 and pcDNA3.1-delTSP2-8CUB1+2 ADAMTS13 were
      introduced into Madin-Darby canine kidney cells (MDCK) by lipofectamine-mediated
      DNA transfection. Positive cell clones gained after antibiotic-screening were
      grown on 6-well transwell filter units with a zeolite membrane in the middle
      layer. The conditioned culture media in both apical and basolateral wells were
      collected when cells reached confluency and the tight cell monolayer formed.
      ADAMTS13 proteases in the conditioned media were determined by Western blot, and
      the direction of ADAMTS13 secretion in polarized cells was comparatively
      analyzed. The results showed that Madin-Darby canine kidney cells stably
      expressing wild-type ADAMTS13 were grown on 6-well transwell filter units, then
      ADAMTS13 protease was only determined in the apical area of the transwell filter
      units by Western blot, but the recombinant ADAMTS13 protease was determined both
      in the apical and basolateral area of cells in the group of expressing TSP2-8CUB
      1+2 domain-deleted ADAMTS13. It is concluded that the metalloprotease ADAMTS13 is
      sorted apically in polarized cells, and the carboxyl-terminal TSP2-8 and CUB1+2
      domains of ADAMTS13 are important for the direction of ADAMTS13 protease
      transportation in the cells after being synthesized.

PMID- 21867625
TI  - [Screening and analysis of coagulation factor VIII inhibitor in patients with
      hemophilia A].
AB  - In order to detect coagulation factor VIII (FVIII) inhibitor in patients with
      severe hemophilia A (HA) and preliminarily study the genetic mutation in patients
      with inhibitor positive. Totally 58 patients with HA (FVIII: C < 1%) were
      enrolled. FVIII: C activity was measured by one-stage coagulation assay. FVIII
      inhibitor was screened by using APTT method and FVIII inhibitor in screened
      positive patients with HA was quantitatively analyzed by using Bethesda method.
      Using genomic DNA as template, 12, 14, 16 exons of FVIII in screened positive
      patients were amplified, and the mutations of amplified products were detected by
      direct sequencing. The results indicated that the FVIII inhibitor could be
      detected in 4 patients (6.9%) from 58 HA patients, no gene mutations in 12, 14,
      16 exons of FVIII were found. It is concluded that the positive rate of FVIII
      inhibitor in HA patients is lower than that reported in literature. The causes of
      inhibitor production needs to further investigate.

PMID- 21867626
TI  - [Diagnosis and influence factor of antibody to coagulation factors in
      hemophilia].
AB  - This study was purposed to investigate the diagnosis, typing and influencing
      factors of the antibody (inhibitor) to coagulation factors in hemophilia. 500
      hemophilia patients were enrolled in this study. The activities of coagulation
      factor FVIII and FIX were tested by one stage assay. The antibodies of FVIII and
      FIX were detected by Bethesda assay. All data were analyzed by statistical soft
      SPSS 10.0. The results indicated that there were 411 cases of hemophilia A, out
      of which 151 cases (30.2%) showed FVIII antibody positive, the titer was 3.50 +/-
      2.84 Bu/ml; there were 79 cases of hemophilia B, out of which 18 cases (3.6%)
      showed FIX antibody positive, the titer was 2.92 +/- 2.19 Bu/ml. The other 10
      cases were acquired autogeneic hemophilia (2.0%). The antibody was divided into
      three types: high-response (3 cases), intermediate-response (47 cases), and low
      response (119 cases). Among the 169 cases with antibody positive, 157 cases
      (92.9%) were younger than 30 years old; among 151 (89.35%) cases of hemophilia A;
      138 cases (81.66%) were moderate or severe hemophilia; 166 case (98.22%) showed
      intermediate or low-response antibody. There were 158 cases with allogeneic
      antibody positive, all of which received blood transfusion. It is concluded that
      the moderate and low responsive antibodies are the dominant in hemophilia
      patients, the age of patients and transfusion frequency of blood preparation are
      the influencing factors. The results of this study provide the basis for the
      hemophilia diagnosis, antibody typing and evaluation of factors influencing
      hemophilia, and also suggest that the repeated transfusion of blood preparation
      may influence the production of antibodies.

PMID- 21867627
TI  - [Secretion of IL-18 and IL-18 binding protein from splenocytes of ITP patients in
      vitro].
AB  - This study was aimed to investigate the expression and clinical significance of
      IL-18, IL-18 binding protein (IL-18BP), IFN-gamma and IL-4 secreted from
      splenocytes of patients with idiopathic thrombocytopenic purpura (ITP) in vitro.
      Spleen mononuclear cells (MNC) were prepared by using routine sterile method, and
      were cultured in RPMI 1640 complete medium containing 10 ug/ml PHA, 10% fetal
      calf serum at 37 degrees C and 5% CO2. The levels of IFN-gamma, IL-4, IL-18 and
      IL-18BP secreted from MNC of ITP patients and normal controls were determined
      after culture for 48 hours. The results showed that after culture of spleen MNC
      for 48 hours, the levels of IL-18 and IFN-gamma were significantly higher in
      patients with ITP than that in controls, but the levels of IL-18BP was not
      significantly elevated in ITP patients. The level of IL-4 was below the
      detectable limit of the assay used. It is concluded that imbalance between IL-18
      and IL-18BP may play an important role in pathogenesis of ITP, and regulation of
      balance between IL-18 and IL-18BP may be a therapeutic approach against ITP.

PMID- 21867628
TI  - [Role of reticulated platelets and platelet-associated antibody in differential
      diagnosis of idiopathic thrombocytopenic purpura].
AB  - The objective of this study was to evaluate the role of reticulated platelets
      (RF) and platelet-associated antibody (PAIg) in differential diagnosis of
      idiopathic thrombocytopenic purpura (ITP). The immature platelet fraction (IPF)
      of 34 ITP patients, 36 non-ITP patients and 411 normal people were detected by
      Sysmex XE-5000 automated blood cell analyser and PAIgG content was detected by
      enzyme-linked immunosorbent assay. All results were analysed statistically. The
      results showed that IPF of ITP patients was significantly higher than that of non
      ITP patients and normal people respectively (p < 0.05). For diagnosis of ITP, IPF
      positive rate of ITP patients was significantly higher than that of non-ITP
      patients (p < 0.05). There was no significant difference between the positive
      rate of PAIgG in ITP and non-ITP patients (p > 0.05). The sensibility,
      specificity and negative predictive value of IPF were higher than those of PAIgG,
      while the positive predictive value of IPF was a little lower than that of PAIgG.
      The area under receiver operating characteristic curve of IPF was larger than
      that of PAIgG. It is concluded that both IPF and PAIgG detection are valuable in
      differential diagnosis of ITP. The diagnostic value of IPF is better than that of
      PAIgG.

PMID- 21867629
TI  - [Comparison of conventional cytogenetics and interphase fluorescence in situ
      hybridization in diagnosis of acute promyelocytic leukemia].
AB  - The aim of this study was to explore cytogenetic characteristics of acute
      promyelocytic leukemia (APL) and compare the interphase fluorescence in situ
      hybridization (I-FISH) with conventional cytogenetic (CC) analysis. A total
      number of 157 APL patients were recruited in this study, and the I-FISH and CC
      were applied to analyze cytogenetic features. Chromosome samples of bone marrow
      cells were prepared by short-term culture. Out of all 157 cases, 136 were
      observed with CC assay, 66 with I-FISH, of which 45 samples were analyzed with
      both methods. The results showed that among all 136 CC samples, t(15;17)(q22;q21)
      was found in 120 cases, of which 107 cases was isolated t(15;17)(q22;q21)
      abnormality, 13 cases was complex abnormalities and 12 case without mitotic
      figure. Among all 66 cases of I-FISH group, PMI/RARalpha fusion gene was found in
      64 cases (97.0%), suggesting that I-FISH group was more sensitive than CC group
      (p = 0.041). It is concluded that combination of I-FISH and CC techniques plays a
      pivotal role for diagnosis and detection of minimal residual disease in APL.

PMID- 21867630
TI  - [Effects of bortezomib combined with methylprednisolone in treatment of 33 cases
      of relapsed or refractory multiple myeloma].
AB  - The aim of this study was to explore the clinical effect and toxicity of
      bortezomib combined with methylprednisolone in treatment of relapsed or
      refractory multiple myeloma (MM). Clinical data of 33 patients (23 male, 10
      female; aged from 38 to 85 years old) were analyzed retrospectively. The median
      diagnosis time was 25 (2 - 120) months. 33 patients received bortezomib (0.9 -
      1.1) mg/m(2) on days 1, 4, 8, 11, in combination with methylprednisolone 40 mg/d
      (4 cases), 80mg/d (13 cases), 120 mg/d (2 cases), 200 mg/d (9 cases), 300 mg/d (5
      cases) respectively. The median follow-up time was 10(3-60) months. The used
      therapy courses were 1 - 8 (mean 4 courses). The results indicated that 24 cases
      showed the response of different degree, the overall response rate (ORR) was
      72.7% (24/33). 32 patients received >= 2 therapy courses, and ORR was 71.9%
      (23/32). 16 patients received 4 therapy courses, and ORR was 93.8% (15/16 cases).
      7 patients received 6 therapy courses and the ORR was 100% (7/7 cases). Main side
      effects were thrombocytopenia, infection and peripheral neuropathy. The median
      survival time was 41.5 (2 - 120) months and the 2-year, 3-year and 5-year overall
      survival rate were 80%, 59.1% and 21.1%, respectively. It is concluded that
      bortezomib combined with methylprednisolone is an effective therapy with higher
      response rate, and safe in treatment of relapsed or refractory multiple myeloma.

PMID- 21867631
TI  - High dose granulocyte colony-stimulating factor enhances survival and
      hematopoietic reconstruction in canines irradiated by 2.3 Gy mixed fission
      neutron and gamma ray.
AB  - This study was purposed to evaluate the effects of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival
      in beagles exposed to mixed fission neutron and gamma-ray. 13 beagles were
      unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were
      divided into 3 groups: irradiation control group (no any treatment, n = 4),
      supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4,
      abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected
      with 200 ug/kg of rhG-CSF early at half an hour and 24 hours post-irradiation
      respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a
      severe acute radiation sickness of bone marrow type. The administration of rhG
      CSF increased the survival rate from 60% in supportive care group to 100%. Twice
      injection of rhG-CSF in the first 24 hours reduced duration of neutropenia,
      enhanced neutrophil nadir and promoted neutrophil recovery when compared with
      control cohort administered clinical support. The number of colony-forming cells
      (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines
      increased 2-to 5-fold relative to those of the supportive care group on day 3.
      All canines treated with rhG-CSF achieved hematopoietic reconstruction as
      evidenced by the pathological section of sternum while severe shortage of
      hemopoietic cells remained in the cohorts given supportive care alone. It is
      concluded that the combination of supportive care and high-dose rhG-CSF can
      accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy
      mixed neutron and gamma ray.

PMID- 21867632
TI  - [Evaluation of methods for detection of NPM1 gene mutations in acute myeloid
      leukemia].
AB  - The purpose of this study was to establish real-time based methods for detection
      of NPM1 gene mutation in acute myeloid leukemia (AML). Primers/probes were
      designed according to the clustered region of NPM1 mutations on exon 12. Two real
      time PCR assays, including high resolution melting curve (HRM) and allele
      specific PCR (AS-PCR), were developed and clinically evaluated with 89 AML
      samples, which were parallelly detected by capillary electrophoresis (CE) and
      sequencing. The results showed that a total of 17 mutation-positive samples were
      detected, including type A (15 cases), type B (1 case) and type Nm (1 case). HRM
      assay could detect all mutant types, and the analytical sensitivity was around
      5%. In contrast, AS-PCR assay detected only 95% mutant types, but its sensitivity
      was as high as 0.01%. It is concluded that considering the characteristics of
      each method as well as the clinical evaluation results, HRM may be used for
      screening of NPM1 mutations at diagnosis, while the AS-PCR can be used for the
      MRD quantification during follow-up.

PMID- 21867633
TI  - [Transcriptional regulation of BHLHB2 induced by PML-RARalpha].
AB  - Objective of this study was to investigate the transcriptional regulation of
      BHLHB2 gene by the PML-RARalpha fusion protein in APL cells and reveal the
      pathogenesis of APL. RT-PCR was performed to detect the expression change of
      BHLHB2 before and after the induction of PML-RARalpha in PR9 cells, and its
      expression level after the treatment of ATRA in PR9 and APL patient derived NB4
      cells. Chromatin immunoprecipitation (ChIP)-based PCR was used to analyze whether
      the BHLHB2 promoter could be bound by PML-RARalpha in vivo. A large-scale gene
      expression profile dataset was used to observe the expression pattern of BHLHB2
      in AML. The results showed that the expression level of BHLHB2 was significantly
      reduced with the induction of PML-RARalpha and ATRA could reverse this inhibition
      in both PR9 and NB4 cells and increase the expression of BHLHB2. However, the
      expression of BHLHB2 could not be induced by ATRA in U937 cells which do not
      express PML-RARalpha. Mechanism study revealed that PML-RARalpha could bound to
      the promoter of BHLHB2 in vivo to regulate the the expression of BHLHB2. It was
      found that the expression of BHLHB2 was relatively lower in APL as compared with
      other subtypes of AML and normal bone marrow cells. It is concluded that BHLHB2
      is the target of PML-RARalpha, and the expression of BHLHB2 is inhibited by PML
      RARalpha through binding to its promoter in APL.

PMID- 21867634
TI  - [Effect of different culture mediums on the development of monocyte-derived
      dendritic cells].
AB  - This study was aimed to investigate the effect of RPMI 1640 and IMDM on the
      development of human peripheral blood monocyte-derived dendritic cells. Under the
      same cytokines and culture conditions, the different medium types were tested,
      and the morphology of mature and immature dendritic cells was observed by
      microscopy, the cell phenotype and endocytosis ability were detected by flow
      cytometry. Furthermore, the immunoregulatory function of various DC was analyzed
      by mixed lymphocyte reaction (MLR), the expression of cytokine in culture
      supernatant of MLR system was also analyzed by Bio-plex technology. The results
      showed that there were no difference in morphology, CD14, CD83 expression and
      endocytosis ability between IMDM-cultured DC and RPMI-1640 medium-cultured DC,
      but there was a lower expression of CD1a in IMDM-cultured DC. Moreover, DC
      cultured with IMDM displayed a significant reduction in stimulating T cell
      proliferation, and highly expressed IL-6, IL-8 and IL-10, but low expressed IL
      12. It is concluded that the different cultural mediums can induce DC with
      different functions and DC cultured with IMDM may correlated with induction of
      immune tolerance. The results of this study will provide a new idea for DC
      clinical application.

PMID- 21867635
TI  - [Expression of perforin in cord blood NK cells after IL-2/IL-15 stimulation and
      its relation with cytotoxicity].
AB  - This study was aimed to investigate the expression level of perforin in cord
      blood NK cells and the relation of perforin expression after IL-2, IL-15
      stimulation to cytotoxicity of NK cells. NK cells were isolated from cord blood
      MNC by depleting CD3(+) cells and then enriching CD56(+) cells using
      immunomagnetic separation (CD3 and CD56 cell isolation kit, autoMACS, miltenyi).
      The purity was analysed by flow cytometry. According to the different combination
      of cytokines, there were two groups: group A (IL-2) and group B (IL-2 + IL-15).
      The cytotoxicity and perforin expression rate of fresh and different cultured CB
      NK cells against K562/Jurkat cell lines were estimated by LDH release test
      (cytotoxic 96 non-radioactive cytotoxicity assay). The results showed that the
      purity of NK cells after separation was more than 90%. The cytotoxicity towards
      both tumor lines in group B was higher than that in group A (p < 0.05), and
      cytotoxicity in group A was higher than that of fresh NK cells (p < 0.05).
      Perforin expression rate of group A (84.55%) was higher than that of fresh NK
      cells (67.21%) (p < 0.05), and there was no significant difference between group
      A and B (84.55% versus 87.22%) Cytotoxic activity of CB-NK cells was positively
      correlated with perforin expression rate (r = 0.886, p < 0.05). It is concluded
      that IL-2 can enhance cytotoxicity of CB/BM-NK cells by increasing the perforin
      expression.

PMID- 21867636
TI  - [Preparation of polyclonal antibody against sAPRIL and analysis of function in
      suppressing sAPRIL-mediated lymphocyte proliferation].
AB  - This study was aimed to prepare the polyclonal antibody against the soluble
      proliferation-inducing ligand (sAPRIL) antigen and to investigate its effects in
      suppressing sAPRIL mediated lymphocyte proliferation. Mutated recombinant sAPRIL
      protein, which lacks biological activity but maintains immunogenicity, was used
      as antigen to immunize humanized SCID mice. Sera were obtained at 6 weeks after
      immunization. Indirect ELISA and Western blot were used to detect the antibody
      titer and specificity. The inhibition of polyclonal antibodies on Raji and Jurkat
      cell proliferation stimulated by sAPRIL was assessed by the MTT assay. The
      results showed that the mutant of sAPRIL could induce the production of
      polyclonal antibodies against human sAPRIL. Western blot and indirect ELISA
      analyses indicated that the anti-serum had higher specificity with a titer of
      1:640. Functional analysis revealed that these polyclonal antibodies
      significantly inhibited the proliferation of Raji and Jurkat cell stimulated by
      sAPRIL (p < 0.05). It is concluded the polyclonal antibody against human sAPRIL
      is successfully prepared, which can inhibit the proliferation of Raji and Jurkat
      cells stimulated by sAPRIL in vitro.

PMID- 21867637
TI  - [Effects of human aorta-gonad-mesonephros region stromal cells on inducing
      differentiation of murine embryonic stem cells into hematopoietic stem/progenitor
      cells in vitro].
AB  - This study was aimed to investigate the effect of human aorta-gonad-mesonephros
      (AGM) region stromal cells on differentiation of murine embryonic stem cells
      (ESC) into hematopoietic stem cells (HSC) in vitro and to clarify their effect
      mechanism. E14 murine ESC were induced into embryo body (EB) firstly. Then the EB
      cells were further co-cultured with the stromal cells from human AGM region,
      fetal liver (FL) or bone marrow (BM) in Transwell non-contact system. According
      to the different culture methods, the EB cells were divided into 6 groups
      including EB control group, AGM group, FL group, BM group, AGM + FL group and AGM
      + BM group. The induced cells derived from EB were collected for Sca-1(+)/c
      Kit(+) cells analysis by flow cytometry and colony forming unit (CFU) assay. The
      results showed that Sca-1(+)/c-Kit(+) cell proportion of EB cells significantly
      increased after being induced by different stromal cells (p < 0.01). The AGM + FL
      group had most Sca-1(+)/c-Kit(+) cells for the positive cell proportion reached
      (21.96 +/- 2.54) % (p < 0.01). The Sca-1(+)/c-Kit(+) cell proportion of AGM + BM
      group was much high than that of BM group too (p < 0.01). The EB control group
      showed CFU amount less than any other groups, while the CFU amount of AGM + FL,
      AGM + BM groups were higher, especially in the AGM + FL group (p < 0.01). It is
      concluded that the human AGM region stromal cells may help to maintain certain
      number of primitive HSC with high proliferation potential. Human AGM region, FL
      or BM stromal cells, applied in sequential orders, can significantly expand in
      vitro the primitive hematopoietic stem/progenitor cells derived from ESC.

PMID- 21867638
TI  - Comparison of hematopoietic supportive capacity between human fetal and adult
      bone marrow mesenchymal stem cells in vitro.
AB  - Hematopoietic stem cells (HSC) shift from fetal liver and spleen to bone marrow
      at neonatal stages and this movement may be due to inductive signals from
      different microenvironments. Mesenchymal stem cells (MSC) are the precursors of
      stromal cells in bone marrow microenvironments such as osteoblasts and
      endothelial cells. Some researchers speculated that fetal bone marrow before
      birth might be not perfectly suit HSC growth. However, it is still lack of direct
      evidence to prove this hypothesis. This study was aimed to compare the
      hematopoietic supportive capacity between human fetal and adult bone marrow MSC
      in vitro. Adult bone marrow MSC (ABM-MSC) were isolated from three healthy donors
      and fetal bone marrow MSC (FBM-MSC) were isolated from three fetuses between
      gestations of 19 to 20 weeks. After irradiation, MSC were co-cultured with
      CD34(+) cells isolated from umbilical cord blood in long-term culture-initiating
      cell (LTC-IC) assay. The colony number of colony forming cells (CFC) was counted
      and the phenotypic changes of co-cultured CD34(+) cells were analyzed by flow
      cytometry. Cytokine expressions in both kinds of MSC were detected by reverse
      transcription polymerase chain reaction (RT-PCR). The results showed that ABM-MSC
      had a stronger hematopoietic supportive capacity than FBM-MSC. Both of them
      enhanced the differentiation of CD34(+) cells into myeloid lineages. Cytokines
      were expressed differently in ABM-MSC and FBM-MSC. It is concluded that ABM-MSC
      possess more potential application in some treatments than FBM-MSC, especially in
      hematopoietic reconstitution.

PMID- 21867639
TI  - [In vitro effects of Wnt3a gene modification on mitigating damage of mouse bone
      marrow mesenchymal stem cells induced by Ara-C].
AB  - This study was aimed to investigate the protective effect of Wit3a gene
      modification on mouse bone marrow mesenchymal stem cells against the injury
      induced by Ara-C. The gene-modified MSC steadily expressing Wnt3a were
      established by adenovirus system. The acute direct damage effects of different
      concentrations of Ara-C on the unmodified MSC and the gene-modified MSC were
      assessed by using an in vitro culture system, and the corresponding controls were
      set. The proliferation and apoptosis of MSC exposed to Ara-C were detected by
      cell count kit-8 (CCK-8) and flow cytometry. The expression of BCL-2 protein
      related with cell apoptosis was assayed by Western blot. The results indicated
      that as compared with unmodified MSC, Ara-C exhibited a less inhibitory effect on
      the proliferation of gene-modified MSC. There was obvious difference between
      unmodified MSC and gene-modified MSC (p < 0.05). The proliferation of gene
      modified MSC began to recover at 72 hours after removal of Ara-C. However,
      unmodified MSC showed sustained suppression of proliferation after withdrawal of
      Ara-C. In apoptosis, the apoptosis rate of gene-modified MSC induced by Ara-C was
      significantly lower than those of unmodified MSC (p < 0.05). In addition, the
      expression levels of BCL-2 protein in gene-modified MSC were up-regulated
      compared with unmodified MSC (p < 0.05). It is concluded that Wnt3a gene
      modification can significantly mitigate the damage of mouse bone marrow MSC
      induced by Ara-C.

PMID- 21867640
TI  - [Establishment of iron overloaded bone marrow model in vitro and its impact on
      hematopoiesis].
AB  - This study was to establish an iron overload bone marrow (BM) model by co
      culturing the mononuclear cells from BM with iron, and investigate its
      hematopoiesis changes. The iron overload model was set up by adding different
      concentration of ferric citrate (FAC) into the mononuclear cells from BM and
      culturing for different time, and the model was confirmed by detecting labile
      iron pool (LIP). Then the apoptosis of hematopoietic cells, ability of
      hematopoietic colony forming (CFU-E, BFU-E, CFU-GM and CFU-mix) and percentage of
      the CD34(+) cells of the BM cells all were determined. The changes of these
      indexes were tested after the iron-overloaded BM was treated with deferasirox
      (DFO). The results showed that after BM cells were cultured with FAC at different
      concentrations for different time, the LIP increased in time-and concentration
      dependent manners. The intracellular LIP reached maximum level when cultured at
      400 umol/L of FAC for 24 hours. The detection of BM cell hematopoietic function
      found that the apoptotic rate of the FAC-treated cells (24.8 +/- 2.99%) increased
      significantly, as compared with normal control (8.9 +/- 0.96%)(p < 0.01). The
      ability of hematopoietic colony forming in FAC-treated cells decreased markedly,
      as compared with normal control (p < 0.05). The percentage of CD34(+) cells of
      FAC-treated cells (0.39 +/- 0.07%) also decreased significantly, as compared with
      normal control (0.91 +/- 0.12%)(p < 0.01). And these changes could be alleviated
      by adding DFO. It is concluded that the iron-overloaded model has been set by
      adding iron into the mononuclear cells from BM in vitro, and the hematopoietic
      function of iron-overloaded BM is deficient. These changes can be alleviated by
      removing the excess iron from the BM cells through treating with DFO. These
      findings would be helpful to further study the mechanism of iron-overload on the
      hematopoiesis of BM and also useful to find the way to treat iron-overload
      patients with hematopoietic disorders.

PMID- 21867641
TI  - [A mouse model of myelofibrosis induced by high dose of recombinant human
      erythropoietin].
AB  - Tn order to set up a mouse model of myelofibrosis (MF) induced with high dose
      recombinant human erythropoietin (rhEPO). 60 mice were collected and divided into
      EPO and control groups, the former was injected with rhEPO and the latter with
      normal saline intraperitoneally. 5 mice from each group were executed on day 6,
      30, 60, 90, 120 and 150 respectively. Their WBC count, Hb level, MCV, RDW and
      platelet amount were measured by automatic blood cell analyzer; CD34(+) cell
      ratio in bone marrow were analyzed by flow cytometry; liver and spleen
      coefficients were measured; pathological changes of liver, spleen, femur were
      observed by HE staining and reticular fibers staining; cortex thickness, femoral
      canal diameter and lumbar spine density were determined by computerized
      tomography (CT). The results indicated that as compared with normal control group
      in EPO induced group, WBC count was increased slightly in whole period, but
      without statistic significance (p > 0.05), Hb level and RDW increased at day 6
      and 30 significantly (p < 0.05), MCV increased at day 6 significantly (p < 0.05),
      but platelet amount decreased significantly at all time points (p < 0.05). Most
      mice in EPO-induced group had hepatomegalia and their liver and spleen
      coefficient increased significantly at day 60 (p < 0.05), while most mice had
      splenomegaly and its coefficient was increased significantly at all time-points
      (p < 0.05). CD43(+) cell ratio of EPO group increased significantly in whole
      period (p < 0.05). CT scanning displayed femoral cortical thickening, medulla
      canal narrowing and lumbar spine density increasing at day 150, meanwhile, HE
      staining and reticular fiber staining showed the fatty degeneration or
      vacuolization in liver, splenomegaly with megakaryocytic proliferation, femur
      bone marrow fibrosis and osteosclerosis. It is concluded that the mouse induced
      by high dose of rhEPO displays the myelofibrosis associated with splenic
      extramedullary hemopoiesis, and this study is useful to establish a practical MF
      model, and to explore its pathological mechanism.

PMID- 21867642
TI  - [Efficiency improvement of fully automatic microcolumn glass sphere technology
      used in blood group compatibility tests].
AB  - The purpose of this study was to determine whether the fully automated ORTHO
      AutoVue Innova system, which based on the microcolumn glass sphere technology, is
      accurate enough to meet immunohematology testing needs at blood banks. 16 IgM
      anti-C, anti-c, anti-D, anti-E and anti-e dilution series were tested
      respectively, with corresponding antigen positive red blood cell solutions, by
      ORTHO AutoVue Innova system and saline medium test. 16 IgG anti-D dilution series
      were tested respectively with RhD positive red blood cell solutions by ORTHO
      AutoVue Innova system, polybrene test and antiglobulin test. The accuracies of
      microcolumn glass sphere technology were analysed, by comparing to the reference
      assays. The results showed that the sensitivities of the ORTHO AutoVue Innova
      tests were 1:69.8, 1:33.4, 1:1448.1, 1:139.6 and 1:32.0 for IgM anti-C, anti-c,
      anti-D, anti-E and anti-e respectively; the corresponding value of saline medium
      tests were 1:16.7, 1:16.6, 1:430.5, 1:34.9 and 1:9.9. There were statistically
      significant differences between the groups of each tests (t values were 14.38,
      5.48, 10.25, 12.65 and 9.59 for IgM anti-C, anti-c, anti-D, anti-E and anti-e
      respectively, p < 0.05). For IgG anti-D, the sensitivities of the ORTHO AutoVue
      Innova test, polybrene test and antiglobulin test were 1:980.6, 1:181.0 and
      1:304.4 respectively. There was statistically significant difference among the 3
      groups (F = 51.15, p < 0.01). It is concluded the use of ORTHO AutoVue Innova
      system for blood group compatibility test can obtain more accurate results than
      traditional tube tests, it is reliable and safe for routine tests performed in
      immunohematology laboratories.

PMID- 21867644
TI  - [Recent progress of study on retroviral mediated mouse model of myeloid leukemia 
      -- review].
AB  - Human leukemia is closely associated with various genetic alterations such as
      chromosomal translocations and gene mutations. The use of retroviral
      transduction/bone marrow transplantation mouse model harboring these genetic
      abnormalities has been critical in understanding the molecular pathogenesis of
      leukemia and exploring new therapeutic target. Additional genetic events are
      verified to cooperate with fusion genes resulting from chromosomal translocations
      in acute myeloid leukemia (AML) to develop a leukemic phenotype in mice, such as
      C-KIT N822K with AML1-ETO, FLT3-ITD with PML-RARalpha, Meis1 with NUP98-HOX, and
      Cdx4 with MLL-AF9. Mouse model shows that BCR/ABL fusion gene induces chronic
      myeloid leukemia (CML), and suggests that GATA-2 L359V and high expression of
      Hes1 are key molecules in acute myeloid transformation of CML. Furthermore,
      combination therapy with Imatinib and arsenic sulfide for CML mice exerts more
      profound therapeutic effects than either drug as a single agent. This review
      focuses the recent progress and application of retroviral-mediated mouse models
      of myeloid leukemia, and discusses some factors influencing the mouse model
      establishment, including retroviral construction, retrovirus titer and
      hematopoietic microenvironment.

PMID- 21867643
TI  - [Influence of cytokine combinations on proliferation and differentiation of
      umbilical cord blood CD34(+) cells into megakaryocytes/platelets in vitro].
AB  - In order to investigate the influence of cytokine combinations on proliferation
      and differentiation of human umbilical cord blood CD34(+) cells into
      megakaryocytes/platelets in vitro, the CD34(+) cells from human umbilical cord
      blood were amplified in serum-free medium StemSpan(SFEM) supplemented with
      several cytokine combinations by three-phase culture system. The effects of the
      cytokine combinations were compared. The results showed that at day 14 of the
      first culture phase, the CD34(+) cells cultured with cytokine combinations SCF +
      TPO + FL + IL-3 were amplified (11 000 +/- 1 000) times, which were significantly
      higher than that of cells cultured with SCF + TPO + FL, but were not
      significantly different from that of cells cultured with SCF + TPO + IL-3 or SCF
      + TPO + FL + IL-3+ hydroxyl-corticosteroids. At day 7 of the second culture
      phase, the CD34(+) cells cultured with cytokine combination SCF + TPO + FL + IL
      11 were amplified by (204666.7 +/- 11718.9) times, which were significantly
      higher than that of cells cultured with SCF + TPO + FL + IL-3, but were not
      significantly different from that of cells cultured with SCF + TPO + FL + IL-11 +
      BMP4 + VEGF. At day 3 and day 6, the CD34(+) platelet-like cells accounted for
      about (39.8 +/- 1.9)%, (39.7 +/- 2.6)% and (25.5 +/- 1.4)%, (23.1 +/- 3.5)%
      cultured with SCF + TPO + FL + IL-11 and SCF + TPO + FL + IL-11 + BMP4 + VEGF,
      and significantly higher than that of the cells cultured with SCF + TPO + FL + IL
      3. It is concluded that the cytokine combination of SCF + TPO + FL + IL-3 is most
      suitable cytokines combination for the amplification of CD34(+) hematopoietic
      progenitor cells. The cytokine combination of SCF + TPO + FL + IL-11 is preferred
      for the proliferation and differentiation of megakaryocytes, this study lays an
      experimental basis for investigating the proliferation and differentiation of
      CD34(+) into megakaryocytes/platelets in vitro.

PMID- 21867645
TI  - Application of tyrosine kinase inhibitors as a promising targeting treatment for
      myeloproliferative neoplasms --- review.
AB  - As well as playing vital roles in main cellular processes, such as abnormal
      proliferation, differentiation, survival, apoptosis, and a lot of tyrosine
      kinases (TK) are involved in oncogenesis. TK or components of their signal
      pathways have been found abnormal in many hematological malignancies. Therefore,
      tyrosine kinase inhibitors (TKI) have been provided a great deal of enthusiasm
      for development of therapy in myeloproliferative neoplasms (MPN).
      Representativity, the treatment of chronic myelogenous leukemia (CML) was
      revolutionary for the design of imatinib mesylate (IM), which is a BCR/ABL TKI.
      Subsequently, because of need for the resistance or intolerance, novel agents are
      being explored and imatinib has now been extended to eosinophilia-associated
      myeloid neoplasms with PDGFRA, PDGFRB or FGFR1 gene mutations. Recently, JAK2
      inhibitor drugs are currently being tested in clinical trials. Here, the current
      review mainly focuses on the role of TK in classic MPN including CML,
      polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia
      (ET), and advances of targeting these abnormalities with small molecule
      inhibitors.

PMID- 21867646
TI  - [Advance of studies on role of miRNA in hematopoietic regulation and
      myeloproliferative neoplasms].
AB  - microRNA (miRNA) are small non-coding RNA molecules of 19 - 25 nucleotides in a
      variety of eukaryotic systems, that control gene expression at the post
      transcriptional level by degrading or translational repressing target messenger
      RNA (mRNA). Many studies have addressed the role of miRNA in normal
      hematopoiesis, giving an interpretative key to the aberrant expression observed
      in human hematological diseases. Here, the advances of main studies on the role
      of miRNA in normal hematopoiesis, and identify the association of miRNA with the
      development, progression of myeloproliferative diseases, including miRNA and
      lymphopoiesis, miRNA and erythropoiesis, miRNA and megakaryopoiesis, miRNA and
      myelopoiesis, miRNA and myeloproliferative neoplasm with positive BCR-ABL-chronic
      myeloid leukemia, miRNA and myeloproliferative neoplasm with negative PCR-ABL
      (PV.IME, ET), and so on are reviewed.

PMID- 21867647
TI  - [Advances of treatment for extranodal NK/T-cell lymphoma --- review].
AB  - Extranodal NK/T-cell lymphoma is a rare pathological type, incidence of which is
      2% - 10% of the primary NHL cases, showing a broad morphologic spectrum with
      frequent necrosis. Extranodal NK/T-cell lymphoma occurs more frequently in Asian
      population, especially in Southern China and Southeast Asian population. It is
      reported that the incidence of ENKL among lymphomas (1314 cases) in Asian
      countries was 4 times as much as the Western countries (22% vs. 5%) by the
      International Peripheral T-cell Lymphoma Project. Nasal NK/T-cell lymphoma most
      commonly occurred in the nasal cavity or other parts of the upper aerodigestive
      tract, and is highly associated with EBV (Epstein-Barr virus) infection, which is
      highly aggressive and its prognosis generally is poor. The mean survival time is
      about 12-38 months. It is important to accurately assess the patients prognosis
      for an optimal treatment. Localized disease (stage I and II) often has a
      relatively good prognosis through local radiation or combined therapy. There is a
      paucity of data to guide therapy in advanced disease. Generally, combining
      therapy is the most commonly selected approach for advanced disease. The
      conditions of the patients with advanced, relapsed or refractory diseases have
      been improved by high-intensity chemotherapy combined with radiation, and a
      regimen containing L-asparaginase L-Asp. Recently some studies have demonstrated
      promising outcomes in the selected cases by high-dose chemotherapy supplemented
      with auto-or allo-HSCT. Targeting therapy is also developing quickly. This
      current review mainly focuses on the advance of treatment for extranodal NK/T
      cell lymphoma.

PMID- 21867648
TI  - [Advance of studies on microRNA and myelodysplastic syndrome].
AB  - MicroRNA (miRNA), evolutionarily conserved, endogenous, small, noncoding RNA
      molecule of about 22 nucleotides in length, have been recently attributed a
      crucial role in numerous physiological and pathological processes including the
      regulation of cellular development, differentiation, proliferation, apoptosis and
      oncogenesis. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal
      hematologic disorders characterized clinically and morphologically by ineffective
      hematopoiesis and increased risk of leukaemic transformation. The role of miRNA
      abnormal expression in pathogenesis and prognosis of MDS is reviewed in this
      article, including miRNA related with pathogenesis, miRNA related with prognosis
      of MDS and so on.

PMID- 21867649
TI  - [Recent development on flow cytometric immunophenotyping study in multiple
      myeloma --- review].
AB  - Multiple myeloma is a common hematological malignancy which is characterized by
      plasma cell malignancies proliferation and osteolysis destruction. It manifests M
      protein, bone destruction, anemia, renal function impairment and immune function
      abnormality. In recent years, researchers have known that flow cytometric
      immunophenotyping is valuable in diagnosis, therapy, prognosis and minimal
      residual disease detection of multiple myeloma. The review summarizes the
      development of flow cytometric immunophenotyping in multiple myeloma, including
      application of flow cytometry in multiple myeloma and immunophenotypic features
      of flow cytometric analysis in multiple myeloma.

PMID- 21867650
TI  - [Progress in classification of hypereosinophilic syndrome --- review].
AB  - Hypereosinophilic syndromes (HES) are a heterogeneous group of uncommon disorders
      which characterized by marked peripheral eosinophilia and function damage of
      target organ, with different etiologies, mechanisms and therapies in different
      subtypes. Formerly the prognosis was very poor, nowadays with great development
      in science and medicine, we can understand HES much better in classification,
      diagnosis and therapy, including the development of novel targeted therapies,
      such as tyrosine kinase inhibitors and humanized monoclonal antibodies, which
      increased the treatment selection and complexity of therapeutic decisions in HES.
      This review discusses the classification of HES and characters of different
      subtypes, including therapeutic methods, which can help clinical doctors to have
      a good understanding of HES.

PMID- 21867651
TI  - [Immune regulation and repair mechanisms of mesenchymal stem cells on incident
      thrombosis in systemic lupus erythematosus --- review].
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease caused by abnormal
      immune regulation and excessive production of autoantibodies, which characterized
      by T and B cell dysfunction and excessive production of pathological cytokines
      and autoantibodies. Vascular endothelia and subendothelial collagen were injured
      by harmful antibodies, so that the body was in a thrombophilic state, increasing
      the multi-system and multi-organ damage of body. Mesenchymal stem cells (MSC) are
      as multipotent cells, capable of multilineage differentiation, self-renewal,
      homing, inflammatory chemotaxis, immune regulation and reconstruction. To date,
      MSC are known to affect not only T cells, but also other cells of the immune
      system. MSC can inhibit or promote B cell proliferation, suppress NK cell
      activation and modulate the cytokine secretion profile of dendritic cells and
      macrophages. Thus decreasing the secretion of harmful cytokines and
      autoantibodies, can ease the thrombosis-prone state of the body, reducing the
      incidence of thrombosis. In addition, MSC are able to differentiate into various
      types of tissue cells, such as hematopoietic cells, endothelial cells, liver
      cells, nerve cells, bone cells, cartilage cells etc, therefore, MSC can repair
      the damaged tissues and organs. In this article, the advance of studies on immune
      regulation and repair mechanisms of MSC on incident thrombosis in SLE is
      reviewed.

PMID- 21867652
TI  - [Acute appendicitis in children--time for improvement].

PMID- 21867653
TI  - [Drug induced hepatotoxicity--don't forget herbals and dietary supplements!].

PMID- 21867654
TI  - [Hepatotoxicity of dietary supplements and herbals is mostly unknown].
AB  - The use of herbals and dietary supplements is considerable and increasing.
      Several cases of serious hepatotoxic side effects and a wide range of clinical
      manifestations have been described. As toxic hepatitis often arises in an
      unpredictable and dose-independent manner, diagnosis may be difficult. Increased
      public awareness of the potential risks of herbals and dietary supplements is
      desirable in order to ensure that suspected adverse effects and interactions are
      formally reported.

PMID- 21867655
TI  - [Hereditary cancer syndromes].
AB  - Hereditary cancer syndromes are characterized by increased risk of cancers but
      other symptoms can also be seen. Germline mutations usually cause a high cancer
      risk but more moderate risk genes are being identified. A negative mutation
      screening cannot exclude a hereditary cancer syndrome, since it is not possible
      to analyse all genes. Genetic diagnostics are now part of clinical management and
      new technology such as next generation sequencing and high-throughput screening
      are being implemented in clinical settings. This will also impose new challenges
      such as identification and interpretation of mutations with unknown significance.

PMID- 21867656
TI  - [Migrant status and access to health-care services in Denmark].
AB  - Access to health-care services in Denmark is dependent on migrant status.
      Emergency care is available to all migrant groups though people not officially
      residing in the country may be subjected to payment. For regular immigrants and
      persons with refugee status access to health-care is regulated by The Health Act,
      whereas access to non-acute health-care for other migrant groups such as asylum
      seekers, undocumented migrants and persons subjected to human being trafficking
      is mainly regulated by The Alien Act. The most vulnerable migrant groups are the
      ones with the most restricted access to care.

PMID- 21867657
TI  - [Fetal and neonatal alloimmune thrombocytopenia].
AB  - Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may lead to intracranial
      haemorrhage (ICH) resulting in neurological damage or death. In FNAIT,
      transplacental maternal antibodies cause destruction of fetal platelets. Maternal
      immunisation occurs to fetal human platelet antigens (HPAs) inherited from the
      father. In the absence of screening the diagnosis often relies on a serious
      incident in a previous pregnancy or in a newborn sibling. Thus, a future
      reduction in the risk of ICH depends on prospective large trials to evaluate
      different diagnostic, treatment, and prevention strategies.

PMID- 21867658
TI  - [Homozygous mutation in the intrinsic factor gene in a child with severe vitamin
      B12 deficiency].
AB  - A 28 month-old boy was hospitalized with pallor and weight stagnation. He had
      macrocytic anaemia and pancytopenia due to cobalamin deficiency and a rare
      homozygous mutation in the intrinsic factor gene. His sister showed similar
      symptoms at the age of 15 months. The heterozygous father had no symptoms, but
      did have a low cobalamin level. Gastroscopy with biopsies showed no pathology.
      All were given monthly cyanocobalamin injections which, however, caused leg
      cramps. Replacement with monthly hydroxocobalamin was successful.

PMID- 21867659
TI  - [Tillaux fracture and fracture of the lateral malleolus with no medial soreness].
AB  - Tillaux fracture is a fracture of the anterolateral tibial epiphysis most often
      seen in children between 11 and 16 years of age. The fracture occurs when the
      medial and central part of the distal tibial epiphysis is closed and the lateral
      part remains open. We present a case with a combination of a Tillaux fracture and
      an ipsilateral fracture of the lateral malleolus in a 16 year-old boy and discuss
      the fracture mechanism using the Lauge-Hansen ankle fracture classification
      system.

PMID- 21867660
TI  - [Recurring pneumothorax due to traumatic rupture of the diaphragm].
AB  - We present a case where a patient is diagnosed with a traumatic right-sided
      diaphragmatic rupture ten years after the trauma, after eight incidences of
      pneumothorax and two thoracoscopic operations. Ten years before the current case,
      the female patient was the victim of a blunt thoraco-abdominal trauma. In the
      following years, she had recurrent right-sided pneumothorax and no effect of
      thoracoscopic surgery. In connection with the third thoracoscopic operation, a
      right-sided diaphragm lesion was discovered. We believe that part of the syndrome
      catamenial pneumothorax, where air is thought to pass through the cervix, could
      explain her condition.

PMID- 21867661
TI  - [Correct treatment of frostbite].
AB  - Frostbite is rare in Denmark and is often associated with psychiatric conditions
      or drug- and alcohol abuse. It is seen regularly in countries with an arctic
      climate and tradition for outdoor activities such as skiing and climbing. The
      past winter in Denmark was long and cold, so we may see this phenomenon more
      frequently in the future. We report two cases from the winter 2009/2010 and
      summarize the pathophysiology and briefly present the treatment strategy.

PMID- 21867662
TI  - [Q-fever caused spontaneous abortion].
AB  - Q-fever is a zoonotic infection. Pregnant women constitute a specific risk group
      as the infection may cause spontaneous abortion, intrauterine death, growth
      retardation, oligohydramnios and premature birth. A 39 year-old veterinarian had
      a spontaneous abortion in pregnancy week seven. During the first weeks of her
      pregnancy, she handled birth by-products from cows with Q-fever. The Q-fever
      titres revealed that she was most likely infected in very early pregnancy.
      According to the literature, infection in the first trimester constitutes a
      specific risk of spontaneous abortion.

PMID- 21867663
TI  - Can asymptomatic patients with a supratherapeutic international normalized ratio
      be safely treated as outpatients?

PMID- 21867664
TI  - The importance of context: evidence that contextual representations increase
      intrusive memories.
AB  - BACKGROUND AND OBJECTIVES: Intrusive memories appear to enter consciousness via
      involuntary rather than deliberate recollection. Some clinical accounts of PTSD
      seek to explain this phenomenon by making a clear distinction between the
      encoding of sensory-based and contextual representations. Contextual
      representations have been claimed to actively reduce intrusions by anchoring
      encoded perceptual data for an event in memory. The current analogue trauma study
      examined this hypothesis by manipulating contextual information independently
      from encoded sensory-perceptual information. METHOD: Participants' viewed images
      selected from the International Affective Picture System that depicted scenes of
      violence and bodily injury. Images were viewed either under neutral conditions or
      paired with contextual information. RESULTS: Two experiments revealed a
      significant increase in memory intrusions for images paired with contextual
      information in comparison to the same images viewed under neutral conditions. In
      contrast to the observed increase in intrusion frequency there was no effect of
      contextual representations on voluntary memory for the images. The vividness and
      emotionality of memory intrusions were also unaffected. LIMITATIONS: The analogue
      trauma paradigm may fail to replicate the effect of extreme stress on encoding
      postulated to occur during PTSD. CONCLUSIONS: These findings question the
      assertion that intrusive memories develop from a lack of integration between
      sensory-based and contextual representations in memory. Instead it is argued
      contextual representations play a causal role in increasing the frequency of
      intrusions by increasing the sensitivity of memory to involuntary retrieval by
      associated internal and external cues.

PMID- 21867665
TI  - The optical spectra of fluoride complexes can effectively probe H-bonding
      interactions in the distal cavity of heme proteins.
AB  - Fluoride complexes of heme proteins are characterized by unique spectroscopic
      properties, that provide a simple and direct means to monitor the interactions of
      the distal heme pocket environment with the iron-bound ligand. In particular, a
      strong correlation has been demonstrated between the wavelength of the iron
      porphyrin charge transfer band at 600-620nm (CT1) and the strength of H-bonding
      donation from the distal amino acid side chains to the fluoride ion. In parallel,
      resonance Raman spectra with excitation within either the CT1 band or the charge
      transfer band at 450-460nm (CT2) have revealed that the iron-fluoride stretching
      frequency is directly affected by H-bonding to the fluoride ion. On this basis,
      globins and peroxidases display distinct spectroscopic features, which are
      strongly dependent on the capability of their distal residues (i.e. histidine,
      arginine and tryptophan) to be involved in H-bonding with the ligand. In
      particular, in peroxidases strong H-bonding corresponds to a low iron-fluoride
      stretching frequency and to a red-shifted CT1 band. The reverse is observed in
      myoglobin. Interestingly, a truncated hemoglobin of microbial origin
      (Thermobifida fusca) investigated in the present work, displays the specific
      spectroscopic signature of a peroxidase, in agreement with the presence of strong
      H-bonding residues, i.e., tyrosine and tryptophan, within the distal pocket.

PMID- 21867667
TI  - Intrabone marrow transplantation of unwashed cord blood using reduced-intensity
      conditioning treatment: a phase I study.
AB  - The outcome of cord blood transplantation following reduced-intensity
      conditioning is suboptimal because of fatal infection triggered by prolonged
      neutropenia and graft-versus-host disease (GVHD) in addition to graft rejection.
      Intrabone marrow injection (IBMI) may improve the outcome by providing better
      hematopoietic engraftment and less GVHD. We therefore evaluated IBMI safety in
      reduced-intensity stem cell transplantation. Furthermore, we used unwashed cord
      blood to avoid stem cell loss. Ten patients (median age = 61 years old) were
      enrolled. Cord blood cells were thawed at the bedside and injected into 4 iliac
      bone sites (2 at each hemipelvis). The procedure was well tolerated with no
      injection-related complications. Nine patients achieved donor engraftment. The
      median time to neutrophil recovery (>0.5 * 10(9)/L) was 17 days, and platelet
      recovery was achieved in 8 patients. Early full donor chimerism was achieved
      (median of 15 and 20 days in T cells and myeloid cells, respectively). Three of 9
      evaluable patients developed grade II to III GVHD, and 5 of 10 patients died of
      treatment-related toxicities. The probability of survival at 1 year was 46.7%.
      IBMI of unwashed cord blood following reduced-intensity conditioning is safe,
      well tolerated, and may lead to an increased donor engraftment rate.

PMID- 21867669
TI  - A high-throughput screen for directed evolution of aminocoumarin amide
      synthetases.
AB  - The biosynthesis of aminocoumarin antibiotics involves the action of amide
      synthetases which construct amide bonds between aminocoumarins and various acyl
      moieties. Libraries of aminocoumarin analogues have been generated by in vivo
      fermentation, via feeding known amide synthetase substrates into producing
      microbial strains. Critically, such feeding studies rely on the inherent or
      engineered substrate promiscuity of each amide synthetase. We have initiated a
      program of directed evolution in order to create mutant amide synthetases for the
      synthesis of new nonnatural amino coumarin analogues. We used the clorobiocin
      enzyme CloL as a model amide synthetase to design and validate a fluorimetric
      high-throughput screen, which can be used to report the activity of mutant amide
      synthetases toward a broad range of coumarin and acyl donor substrates. Our assay
      monitors the decrease in fluorescence of aminocoumarins on acylation. The utility
      of the assay was illustrated by screening a library of amide synthetase mutants
      created by error-prone PCR. The substrate specificity of an amide synthetase was
      also rapidly probed using this assay, affording several newly identified
      substrates. It is anticipated that this high-throughput screen will accelerate
      the creation of amide synthetase mutants with new specificities by directed
      evolution.

PMID- 21867666
TI  - Long-term follow-up of allogeneic hematopoietic stem cell transplantation for
      patients with Philadelphia chromosome-positive acute lymphoblastic leukemia:
      impact of tyrosine kinase inhibitors on treatment outcomes.
AB  - The introduction of tyrosine kinase inhibitors (TKI) has revolutionized therapy
      for patients with acute lymphoblastic leukemia (ALL) who have the Philadelphia
      (Ph) chromosome. A retrospective analysis was conducted on 102 adults and 11
      children who received a first-matched related (n = 60), matched unrelated (n =
      40), mismatched cord blood (n = 12), or haploidentical (n = 1) allogeneic
      hematopoietic stem cell transplantation (HSCT) for Ph-positive (Ph+) ALL in first
      complete remission (n = 71), second complete remission (n = 11), or with active
      disease (n = 31) between 1990 and 2009. Sixty-seven patients received TKI with
      upfront ALL therapy, and 32 patients received TKI maintenance following HSCT.
      With median follow-up of 5 years among survivors (range: 1.1-20.4 years), overall
      survival (OS) was significantly better for patients transplanted in first
      remission compared with HSCT in advanced disease: 43% versus 16%, P = .002.
      Disease stage and age at time of HSCT, the development of acute graft-versus-host
      disease (aGVHD), and decade of HSCT were found to significantly impact OS,
      progression-free survival (PFS), and nonrelapse mortality (NRM) in multivariate
      analyses. Allogeneic HSCT provides durable remission for patients with Ph+ ALL in
      first remission. Neither TKI use pre- nor post-HSCT were found to significantly
      impact transplant outcomes in univariate and multivariate analyses.

PMID- 21867670
TI  - Display of disulfide-rich proteins by complementary DNA display and disulfide
      shuffling assisted by protein disulfide isomerase.
AB  - We report an efficient system to produce and display properly folded disulfide
      rich proteins facilitated by coupled complementary DNA (cDNA) display and protein
      disulfide isomerase-assisted folding. The results show that a neurotoxin protein
      containing four disulfide linkages can be displayed in the folded state.
      Furthermore, it can be refolded on a solid support that binds efficiently to its
      natural acetylcholine receptor. Probing the efficiency of the display proteins
      prepared by these methods provided up to 8-fold higher enrichment by the
      selective enrichment method compared with cDNA display alone, more than 10-fold
      higher binding to its receptor by the binding assays, and more than 10-fold
      higher affinities by affinity measurements. Cotranslational folding was found to
      have better efficiency than posttranslational refolding between the two
      investigated methods. We discuss the utilities of efficient display of such
      proteins in the preparation of superior quality proteins and protein libraries
      for directed evolution leading to ligand discovery.

PMID- 21867671
TI  - Differential analysis of "protein corona" profile adsorbed onto different
      nonviral gene delivery systems.
AB  - A shotgun proteomics approach was used to characterize and compare the proteins
      that lead to the formation of a rich "protein corona" adsorbed onto the surfaces
      of cationic liposomes (CLs), lipoplexes, and lipid/polycation/DNA (LPD)
      complexes, when they come into contact with plasma. After separation of the
      nanoparticle-protein complex from plasma, the protein mixture was digested, and
      peptides were analyzed by nanoliquid chromatography-Orbitrap LTQ-XL mass
      spectrometry. The number of proteins bound to lipoplexes was double that of those
      identified in the corona of CLs (208 vs 105), while 77 proteins were common to
      both coronas. The number of proteins bound to the surface of the LPD complexes
      (158, 133 of which are common to lipoplexes) is intermediate between those found
      in the protein corona of both CLs and lipoplexes. About half of them were found
      in the protein corona of CLs. By overlapping the three formulations, it can be
      seen that only 12 proteins are peculiar to LPD complexes. These results may help
      in designing gene delivery systems capable of binding the minimum possible
      quantity of proteins that influence transfection negatively, binding selectively
      proteins capable of helping in steering in vivo the vector toward the target, and
      obtaining more efficient and effective gene therapy.

PMID- 21867672
TI  - Fluorogenic cephalosporin substrates for beta-lactamase TEM-1.
AB  - Cephalosporin was used to synthesize soluble and precipitating fluorogenic beta
      lactam substrates that demonstrated differential catalytic hydrolysis by three
      different subtypes of beta-lactamase: TEM-1 (class A), p99 (class C), and a
      Bacillus cereus enzyme sold by Genzyme (class B). The most successful soluble
      substrate contained difluorofluorescein (Oregon Green 488) ligated to two
      cephalosporin moieties that, therefore, required two turnovers to produce the
      fluorescent Oregon Green 488 leaving group. The bis-cephalosporin modification
      was required so that the final reaction product was the Oregon Green 488
      carboxylic acid rather than a less bright phenolic adduct of the dye. Hydrolysis
      in pH 5.5 Mes and pH 7.2 phosphate-buffered saline (PBS) buffers was similar, but
      in pH 8.0 Tris the hydrolysis rate nearly doubled. Activity of the beta
      lactamases on the various substrates was shown to depend highly on the linker
      between the cephalosporin and the fluorophore, with an allyl linker promoting
      faster turnover than a phenol ether linker. Measured K(m) values for
      dichlorofluorescein and difluorofluorescein cephalosporin substrates were
      approximately the same as K(m) values for penicillin G and ampicillin found in
      the literature (~30-40MUM).

PMID- 21867673
TI  - An improved method for quantitative analysis of total fructans in plant tissues.
AB  - Current methods for measuring fructan levels in plant tissues are time-consuming
      and costly. They often involve multiple or sequential extractions, enzymatic or
      acid hydrolysis of fructan polymers, and multiple HPLC runs to quantify fructan
      derived hexoses. Here we describe a new method that requires a single extraction
      step, followed by selective precipitation of fructans by acetone, acid hydrolysis
      of the precipitate, and a short (10 min) HPLC run to complete the procedure. We
      used perennial ryegrass samples to show that the new method has similar
      sensitivity, but better reproducibility, than a more complex method that is
      widely used. We have used the new method to study developmentally related changes
      in fructan levels in glasshouse-grown perennial ryegrass plants.

PMID- 21867674
TI  - On-line characterization of monoclonal antibody variants by liquid chromatography
      mass spectrometry operating in a two-dimensional format.
AB  - Recombinant monoclonal antibodies (MAbs) have become one of the most rapidly
      growing classes of biotherapeutics in the treatment of human disease. MAbs are
      highly heterogeneous proteins, thereby requiring a battery of analytical
      technologies for their characterization. However, incompatibility between
      separation and subsequent detection is often encountered. Here we demonstrate the
      utility of a generic on-line liquid chromatography-mass spectrometry (LC-MS)
      method operated in a two-dimensional format toward the rapid characterization of
      MAb charge and size variants. Using a single chromatographic system capable of
      running two independent gradients, up to six fractions of interest from an ion
      exchange (IEC) or size exclusion (SEC) separation can be identified by trapping
      and desalting the fractions onto a series of reversed phase trap cartridges with
      subsequent on-line analysis by mass spectrometry. Analysis of poorly resolved and
      low-level peaks in the IEC or SEC profile was facilitated by preconcentrating
      fractions on the traps using multiple injections. An on-line disulfide reduction
      step was successfully incorporated into the workflow, allowing more detailed
      characterization of modified MAbs by providing chain-specific information. The
      system is fully automated, thereby enabling high-throughput analysis with minimal
      sample handling. This technology provides rapid data turnaround time, a much
      needed feature during product characterization and development of multiple
      biotherapeutic proteins.

PMID- 21867675
TI  - Inhibition of mitochondrial respiration by phosphoenolpyruvate.
AB  - The cytosolic factors that influence mitochondrial oxidative phosphorylation
      rates are relatively unknown. In this report, we examine the effects of
      phosphoenolpyruvate (PEP), a glycolytic intermediate, on mitochondrial function.
      It is reported here that in rat heart mitochondria, PEP delays the onset of state
      3 respiration in mitochondria supplied with either NADH-linked substrates or
      succinate. However, the maximal rate of state 3 respiration is only inhibited
      when oxidative phosphorylation is supported by NADH-linked substrates. The
      capacity of PEP to delay and/or inhibit state 3 respiration is dependent upon the
      presence or absence of ATP. Inhibition of state 3 is exacerbated in uncoupled
      mitochondria, with a 40% decrease in respiration seen with 0.1mM PEP. In
      contrast, ATP added exogenously or produced by oxidative phosphorylation
      completely prevents PEP-mediated inhibition. Mechanistically, the results support
      the conclusion that the main effects of PEP are to impede ADP uptake and inhibit
      NADH oxidation. By altering the NADH/NAD(+) status of mitochondria, it is
      demonstrated that PEP enhances succinate dehydrogenase activity and increase free
      radical production. The results of this study indicate PEP may be an important
      modulator of mitochondrial function under conditions of decreased ATP.

PMID- 21867676
TI  - AMP-activated protein kinase modulates the gene expression of aquaporin 9 via
      forkhead box a2.
AB  - Aquaporin 9 (AQP9) is permeable to glycerol, which is a source material in
      lipogenesis and gluconeogenesis in the liver. We investigated the transcriptional
      regulation of the AQP9 gene by AMP-activated protein kinase (AMPK), known as an
      energy sensor in cells since AMPK contributes to the metabolism of carbohydrate,
      lipid, and protein by regulating the expression of many enzymes and transcription
      factors in metabolic pathways. An AMPK activator, 5-aminoimidazole-4-carboxamide
      1-beta-d-ribonucleoside (AICAR), was observed to suppress the expression of the
      AQP9 gene in HepG2 cells by promoting the phosphorylation of AMPK and AKT/PKB.
      Forkhead box a2 (Foxa2) was speculated to be one of the transcriptional
      regulators of AQP9 gene expression repressed by AICAR from the results of a
      reporter gene assay with a plasmid containing the promoter region of the AQP9
      gene and knock-down of the Foxa2 gene by a specific siRNA. AICAR was determined
      to induce the phosphorylation and nuclear exclusion of Foxa2. Leptomycin B,
      inhibiting the binding of the nuclear exclusion signal sequence and chromosome
      region maintenance 1, prevented nuclear export of Foxa2 triggered by AICAR. These
      results suggest that the activated AMPK by AICAR causes suppression of the gene
      expression of AQP9 through transcriptional regulation by Foxa2.

PMID- 21867677
TI  - Protein molecular function influences mutation rates in human genetic diseases
      with allelic heterogeneity.
AB  - Molecular epidemiology studies have used the counts of different mutational types
      like transitions, transversions, etc. to identify putative mutagens, with little
      reference to gene organization and structure-function of the translated product.
      Moreover, geographical variation in the mutational spectrum is not limited to the
      mutational types at the nucleotide level but also have a bearing at the
      functional level. Here, we developed a novel measure to estimate the rate of
      spontaneous detrimental mutations called "mutation index" for comparing the
      mutational spectra consisting of all single base, missense, and non-missense
      changes. We have analyzed 1609 mutations occurring in 38 exons in 24 populations
      in three diseases viz. hemophilia B (F9 gene - 420 mutations in 9 populations
      across 8 exons), hemophilia A (F8 gene - 650, 8 and 26, respectively) and ovarian
      carcinoma (TP53 gene - 539, 7 and 4, respectively). We considered exons as units
      of evolution instead of the entire gene and observed feeble differences among
      populations implying lack of a mutagen-specific effect and the possibility of
      mutation causing endogenous factors. In all the three genes we observed elevated
      rates of detrimental mutations in exons encoding regions of significance for the
      molecular function of the protein. We propose that this can be extended to the
      entire exome with implications in exon-shuffling and complex human diseases.

PMID- 21867678
TI  - Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and
      invasion in U87 glioma cells.
AB  - Phospholipase D (PLD) has been recognized as a regulator of cell proliferation
      and tumorigenesis, but little is known about the molecules regulating PLD
      expression. Thus, the identification of small molecules inhibiting PLD expression
      would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous
      bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a
      variety of cancer cells. In the present study, we examined the effect of
      quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly
      suppressed the expression of PLD1 at the transcriptional level. Moreover,
      quercetin abolished the protein expression of PLD1 in a time and dose-dependent
      manner, as well as inhibited PLD activity. Quercetin suppressed NFkappaB-induced
      PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin
      inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator
      of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD
      activity. Taken together these data demonstrate that quercetin abolishes PLD1
      expression and subsequently inhibits invasion and proliferation of glioma cells.

PMID- 21867679
TI  - The plant cell death suppressor Adi3 interacts with the autophagic protein Atg8h.
AB  - The tomato AGC protein kinase Adi3 is known to function as a suppressor of PCD
      and silencing of Adi3 leads to spontaneous cell death on leaves and stems. In an
      effort to isolate Adi3 interacting proteins, a yeast two-hybrid screen was
      carried out and identified the autophagy protein Atg8h as an Adi3 interactor.
      This interaction occurred independent of the kinase activity status of Adi3.
      Silencing of genes involved in autophagy is known to eliminate the restriction of
      pathogen-induced PCD to a few cells and leads to run away PCD. Cosilencing Adi3
      with several autophagy genes lead to the same run away cell death suggesting Adi3
      may be involved in autophagic regulation of PCD.

PMID- 21867680
TI  - Transcription of the Tollip gene is elevated in intestinal epithelial cells
      through impaired O-GlcNAcylation-dependent nuclear translocation of the negative
      regulator Elf-1.
AB  - Intestinal epithelial cells (IECs) must be tolerant of the large number of
      commensal bacteria inhabiting the intestinal tract to avoid excessive
      inflammatory reactions. Toll-interacting protein (Tollip), a negative regulator
      of Toll-like receptor signaling, is known to be expressed at high levels in IECs,
      and to thereby contribute to the hyporesponsiveness of IECs to commensals. In
      this study, we analyzed the underlying mechanisms for elevated transcription of
      the Tollip gene in IECs using a human IEC line, Caco-2, and a human monocyte
      line, THP-1, as a control. Elf-1 was identified as a transcription factor that
      negatively regulates Tollip gene expression. The transcription factor Elf-1 was
      localized in the nucleus by O-linked N-acetylglucosamine (O-GlcNAc) modification,
      whereas the unmodified form was detected only in the cytoplasm. Comparison of
      Caco-2 and THP-1 cells revealed that O-GlcNAc modification of Elf-1 was
      significantly lower in IECs than in monocytes. Collectively, the results indicate
      that insufficient O-GlcNAc modification prevents Elf-1-mediated transcriptional
      repression and thereby upregulates Tollip gene expression in IECs.

PMID- 21867681
TI  - Introduction of a negative charge at Arg82 in thaumatin abolished responses to
      human T1R2-T1R3 sweet receptors.
AB  - Thaumatin, an intensely sweet-tasting protein, elicits a sweet-taste sensation at
      a level as low as 50 nM. Although previous sensory analyses have suggested that
      Lys67 and Arg82 are important to the sweetness of thaumatin, the exact effects of
      each residue on sweet receptors are still unknown. In the present study, various
      mutants of thaumatin altered at Arg82 as well as Lys67 were prepared and their
      sweetness levels were quantitatively evaluated by cell-based assays using HEK293
      cells expressing human sweet receptors. Mutations at Arg82 had a more
      deteriorative effect on sweetness than mutations at Lys67. Particularly, a charge
      inversion at Arg82 (R82E) resulted in an abolishment of the response to sweet
      receptors even at a concentration as high as 1mM. These results indicate that
      Arg82 plays a central role in determining the sweetness of thaumatin. A strict
      spatial charge location at residue 82 appears to be required for interaction with
      sweet receptors.

PMID- 21867682
TI  - Endoplasmic reticulum is a main localization site of mTORC2.
AB  - The Akt kinase is a critical effector in growth factor signaling. Activation of
      Akt driven by the growth factor dependent PI3K (phosphatidylinositol-3-OH kinase)
      is coupled to the plasma membrane translocation and phosphorylation of Akt on two
      sites by PDK1 (phosphoinositide-dependent protein kinase-1) on Thr-308 and by
      mTORC2 (mammalian Target of Rapamycin Complex 2) on Ser-473. In our study we
      examined the sub-cellular localization of mTORC2 and identified that this kinase
      complex predominantly resides on endoplasmic reticulum (ER). Our immunostaining
      analysis did not show a substantial co-localization of the mTORC2 component
      rictor with Golgi, lysosome, clathrin-coated vesicles, early endosomes, or plasma
      membrane but indicated a strong co-localization of rictor with ribosomal protein
      S6 and ER marker. Our biochemical study also identified the mTORC2 components
      rictor, SIN1, and mTOR as the highly abundant proteins in the ER fraction,
      whereas only small amount of these proteins are detected in the plasma membrane
      and cytosolic fractions. We found that growth factor signaling does not alter the
      ER localization of mTORC2 and also does not induce its translocation to the
      plasma membrane. Based on our study we suggest that the mTORC2-dependent
      phosphorylation of Akt on Ser-473 takes place on the surface of ER.

PMID- 21867683
TI  - The human insulin mRNA is partly translated via a cap- and eIF4A-independent
      mechanism.
AB  - The aim of this study was to investigate whether cap-independent insulin mRNA
      translation occurs in human pancreatic islets at basal conditions, during
      stimulation at a high glucose concentration and at conditions of nitrosative
      stress. We also aimed at correlating cap-independent insulin mRNA translation
      with binding of the IRES trans-acting factor polypyrimidine tract binding protein
      (PTB) to the 5'-UTR of insulin mRNA. For this purpose, human islets were
      incubated for 2h in the presence of low (1.67 mM) or high glucose (16.7 mM).
      Nitrosative stress was induced by addition of 1 mM DETA/NO and cap-dependent mRNA
      translation was inhibited with hippuristanol. Insulin biosynthesis rates were
      determined by radioactive labeling and immunoprecipitation. PTB affinity to
      insulin mRNA 5'-UTR was assessed by a magnetic micro bead pull-down procedure. We
      observed that in the presence of 1.67 mM glucose, approximately 70% of the
      insulin mRNA translation was inhibited by hippuristanol. Corresponding value from
      islets incubated at 16.7 mM glucose was 93%. DETA/NO treatment significantly
      decreased the translation of insulin by 85% in high glucose incubated islets, and
      by 50% at a low glucose concentration. The lowered insulin biosynthesis rates of
      DETA/NO-exposed islets were further suppressed by hippuristanol with 55% at 16.7
      mM glucose but not at 1.67 mM glucose. Thus, hippuristanol-induced inhibition of
      insulin biosynthesis was less pronounced in DETA/NO-treated islets as compared to
      control islets. We observed also that PTB bound specifically to the insulin mRNA
      5'-UTR in vitro, and that this binding corresponded well with rates of cap
      independent insulin biosynthesis at the different conditions. In conclusion, our
      studies show that insulin biosynthesis is mainly cap-dependent at a high glucose
      concentration, but that the cap-independent biosynthesis of insulin can
      constitute as much as 40-100% of all insulin biosynthesis during conditions of
      nitrosative stress. These data suggest that the pancreatic beta-cell is able to
      uphold basal insulin synthesis at conditions of starvation and stress via a cap-
      and eIF4A-independent mechanism, possibly mediated by the binding of PTB to the
      5'-UTR of the human insulin mRNA.

PMID- 21867684
TI  - Suppression of L-type Ca2+ current by fluid pressure in rat ventricular myocytes:
      possible role of Cl(-)-OH(-) exchange.
AB  - The application of fluid pressure (FP) in ventricular myocytes using pressurized
      fluid flow inhibits L-type Ca(2+) current (I(Ca)), with approximately 80% of this
      effect coming through the enhancement of Ca(2+) releases from the sarcoplasmic
      reticulum. In the present study, we explored the remaining mechanisms for the
      inhibition of I(Ca) by FP. Since FP significantly increases H(+) concentration
      and H(+) is known to inhibit I(Ca), we examined whether pH regulation plays a
      role in the inhibitory effect by FP on I(Ca). A flow of pressurized (~16.3
      dyne/cm(2)) fluid, identical to that bathing the myocytes, was applied onto
      single rat ventricular myocytes for which the I(Ca) was monitored using whole
      cell patch-clamp under HEPES-buffered conditions. Extracellular application of
      the alkalizing agent, NH(4)Cl (20 mM), enhanced I(Ca) by ~34% in the control
      conditions while increasing I(Ca) significantly less (by ~21%) in FP-pretreated
      myocytes, suggesting an inhibition of the effect of NH(4)Cl on I(Ca) possibly by
      FP-induced acidosis. Application of DIDS (4,4'-diisothiocyanatostilbene-2,2'
      disulphonic acid, 500MUM), which blocks Cl(-)-HCO(3)(-) exchange but not Cl(-)
      OH(-) exchange, did not alter the inhibitory effect of FP on I(Ca). Replacement
      of external Cl(-) with aspartate attenuated the inhibitory effect of FP on I(Ca).
      In highly Ca(2+)-buffered cells, where Ca(2+)-dependent inhibition of I(Ca) was
      minimized, the external Cl(-) removal eliminated the inhibitory effect of FP on
      I(Ca). These results suggest that the decrease of I(Ca) in the presence of FP is
      at least partly caused by intracellular acidosis via activation of Cl(-)-OH(-)
      exchange in rat ventricular myocytes.

PMID- 21867685
TI  - Characterization of novel antimicrobial peptides from the skin of the endangered
      frog Odorrana ishikawae by shotgun cDNA cloning.
AB  - We recently reported the primary structures, antimicrobial activities and cDNA
      precursors of nine novel antimicrobial peptides from the skin of the endangered
      anuran species, Odorranaishikawae. Their cDNA clones revealed a highly conserved
      approximately 60 bp region upstream of the start codon. This conserved region was
      used in the "shotgun" cDNA cloning method to reveal additional cDNAs encoding
      novel antimicrobial peptides of O.ishikawae. After sequencing 344 clones, we
      identified novel 13 cDNAs encoding dermal peptides in addition to the previously
      identified nine antimicrobial peptides. These 13 unique cDNAs encoded precursor
      proteins each containing a signal peptide, an N-terminal acidic spacer domain, a
      Lys-Arg/Lys processing site and a dermal peptide at the C-terminus. The dermal
      peptides were members of the palustrin-2 (two peptides; termed palustrin-2ISc and
      palustrin-2ISd), nigrocin-2 (one peptide; nigrocin-2ISc), brevinin-1 (one
      peptide; brevinin-1ISa), odorranain-M (one peptide; odorranain-MISa) and entirely
      novel peptides (eight peptides; ishikawain-1-8). Although palustrin-2ISd and
      odorranain-MISa had few antimicrobial activities, palustrin-2ISc and nigrocin
      2ISc possessed a broad-spectrum of growth inhibition against bacteria. Brevinin
      1ISa had the most potent antimicrobial activities against the Gram-positive
      bacteria and the fungus but not the Gram-negative bacterium, Escherichiacoli.
      However, eight novel peptides showed no growth inhibition against these
      microorganisms.

PMID- 21867686
TI  - Folic acid supplementation dysregulates gene expression in lymphoblastoid cells-
      implications in nutrition.
AB  - For over a decade, folic acid (FA) supplementation has been widely prescribed to
      pregnant women to prevent neural tube closure defects in newborns. Although
      neural tube closure occurs within the first trimester, high doses of FA are given
      throughout pregnancy, the physiological consequences of which are unknown. FA can
      cause epigenetic modification of the cytosine residues in the CpG dinucleotide,
      thereby affecting gene expression. Dysregulation of crucial gene expression
      during gestational development may have lifelong adverse effects or lead to
      neurodevelopmental defects, such as autism. We have investigated the effect of FA
      supplementation on gene expression in lymphoblastoid cells by whole-genome
      expression microarrays. The results showed that high FA caused dysregulation by
      >= four-fold up or down to more than 1000 genes, including many imprinted genes.
      The aberrant expression of three genes (FMR1, GPR37L1, TSSK3) was confirmed by
      Western blot analyses. The level of altered gene expression changed in an FA
      concentration-dependent manner. We found significant dysregulation in gene
      expression at concentrations as low as 15 ng/ml, a level that is lower than what
      has been achieved in the blood through FA fortification guidelines. We found
      evidence of aberrant promoter methylation in the CpG island of the TSSK3 gene.
      Excessive FA supplementation may require careful monitoring in women who are
      planning for, or are in the early stages of pregnancy. Aberrant expression of
      genes during early brain development may have an impact on behavioural
      characteristics.

PMID- 21867687
TI  - Amino acid deprivation regulates the stress-inducible gene p8 via the GCN2/ATF4
      pathway.
AB  - In mammals, the GCN2/ATF4 pathway has been described as the main pathway involved
      in the regulation of gene expression upon amino acid limitation. This regulation
      is notably conferred by the presence of a cis-element called Amino Acid Response
      Element (AARE) in the promoter of specific genes. In vivo, the notion of amino
      acid limitation is not limited to nutritional context, indeed several
      pathological situations are associated with alteration of endogenous amino acid
      availability. This is notably true in the context of tumour in which the
      alteration of the microenvironment can lead to a perturbation in nutrient
      availability. P8 is a small weakly folded multifunctional protein that is
      overexpressed in several kinds of cancers and whose expression is induced by
      different stresses. In this study we have demonstrated that amino acid starvation
      was also able to induce p8 expression. Moreover, we brought the evidence, in
      vitro and in vivo, that the GCN2/ATF4 pathway is involved in this regulation
      through the presence of an AARE in p8 promoter.

PMID- 21867688
TI  - Extremely low polymerizability of a highly-divergent Chlamydomonas actin (NAP).
AB  - Novel actin-like protein (NAP) is a highly divergent actin expressed in
      Chlamydomonas. With its low sequence similarity, it is uncertain whether NAP can
      polymerize into filaments. Here I assessed it by ectopically expressing enhanced
      green fluorescent protein-tagged NAP (EGFP-NAP) in cultured cells. EGFP-NAP was
      excluded from stress fibres but partially co-localized with endogenous actin in
      the cell periphery. In fluorescence recovery after photobleaching experiment,
      turnover rate of EGFP-NAP was similar to the estimated diffusion rate of
      monomeric actin. Therefore, EGFP-NAP likely accumulates by diffusion. These
      findings suggest that NAP has extremely poor ability to polymerize.

PMID- 21867689
TI  - Combined stimulation with cyclic stretching and hypoxia increases production of
      matrix metalloproteinase-9 and cytokines by macrophages.
AB  - Macrophages in the vessel wall of advanced abdominal aortic aneurysms (AAAs) are
      subjected to cyclic stretching and hypoxia because of pulsatile blood flow and
      intraluminal thrombi, respectively. It is possible that these conditions induce
      abnormal changes in macrophage functions, such as increased production of matrix
      metalloproteinase-2 (MMP-2), MMP-9, and inflammatory cytokines, leading to
      weakening of the aortic wall through excessive extracellular matrix disruption.
      Here we show the effects of cyclic stretching and hypoxia on the production of
      MMP-9 and inflammatory cytokines by macrophages. Gelatin zymography revealed that
      MMP-9 production by macrophages was significantly increased by 5% and 10% cyclic
      stretching under hypoxia (2.2% O(2)). Using enzyme-linked immunosorbent assay, we
      also evaluated the production of 12 different inflammatory cytokines and found
      that there was a tendency toward higher expressions of interleukin-8 and tumor
      necrosis factor-alpha by macrophages subjected to 10% cyclic stretching under
      normoxia and hypoxia. Next, we evaluated apoptosis of smooth muscle cells (SMCs)
      in medium conditioned by macrophages cultured under the 2 conditions described
      above. SMC apoptosis increased significantly when exposed to media harvested from
      macrophages subjected to 10% cyclic stretching under normoxia and hypoxia. On the
      basis of these results, we believe that macrophages produce cytokines that induce
      SMC apoptosis. Our results suggest that the combination of cyclic stretching and
      hypoxia stimulates MMP-9 and cytokine production in macrophages, which may result
      in weakening of AAA walls.

PMID- 21867690
TI  - Matrix vesicles isolated from mineralization-competent Saos-2 cells are
      selectively enriched with annexins and S100 proteins.
AB  - Matrix vesicles (MVs) are cell-derived membranous entities crucial for mineral
      formation in the extracellular matrix. One of the dominant groups of constitutive
      proteins present in MVs, recognised as regulators of mineralization in norm and
      pathology, are annexins. In this report, besides the annexins already described
      (AnxA2 and AnxA6), we identified AnxA1 and AnxA7, but not AnxA4, to become
      selectively enriched in MVs of Saos-2 cells upon stimulation for mineralization.
      Among them, AnxA6 was found to be almost EGTA-non extractable from matrix
      vesicles. Moreover, our report provides the first evidence of annexin-binding
      S100 proteins to be present in MVs of mineralizing cells. We observed that
      S100A10 and S100A6, but not S100A11, were selectively translocated to the MVs of
      Saos-2 cells upon mineralization. This observation provides the rationale for
      more detailed studies on the role of annexin-S100 interactions in MV-mediated
      mineralization.

PMID- 21867691
TI  - Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.
AB  - We present evidence for potential biomarker utility of a mitochondrial complex I
      subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma
      specimens obtained from clinical patients. Besides being a robust indicator of
      breast cancer aggressiveness, NDUFS3 also shows clear signatures of a
      hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically
      significant positive correlation was observed between nuclear grade and NDUFS3
      expression level in the tumor specimens analyzed. We support these findings with
      a plausible mechanism involving mitochondrial complex I assembly defects and/or
      redox buffering induced mitochondrial dysfunction during the process of cancer
      cell transformation. From a clinical standpoint, this novel observation adds
      value in augmenting the current receptor-based biomarkers for better accuracy in
      diagnosis and predicting survival rate in patients with breast carcinoma.

PMID- 21867692
TI  - Fluorescent metal nanoshell and CK19 detection on single cell image.
AB  - In this article, we report the synthesis strategy and optical properties of a
      novel type of fluorescence metal nanoshell when it was used as imaging agent for
      fluorescence cell imaging. The metal nanoshells were made with 40 nm silica cores
      and 10nm silver shells. Unlike typical fluorescence metal nanoshells which
      contain the organic dyes in the cores, novel metal nanoshells were composed of
      Cy5-labelled monoclonal anti-CK19 antibodies (mAbs) on the external surfaces of
      shells. Optical measurements to the single nanoparticles showed that in
      comparison with the metal free labelled mAbs, the mAb-Ag complexes displayed
      significantly enhanced emission intensity and dramatically shortened lifetime due
      to near-field interactions of fluorophores with metal. These metal nanoshells
      were found to be able to immunoreact with target cytokeratin 19 (CK19) molecules
      on the surfaces of LNCAP and HeLa cells. Fluorescence cell images were recorded
      on a time-resolved confocal microscope. The emissions from the metal nanoprobes
      could be clearly isolated from the cellular autofluorescence backgrounds on the
      cell images as either individuals or small clusters due to their stronger
      emission intensities and shorter lifetimes. These emission signals could also be
      precisely counted on single cell images. The count number may provide an approach
      for quantifying the target molecules in the cells.

PMID- 21867694
TI  - Mass spectrometry-based plasma peptide profiling of acute exacerbation in HBeAg
      positive chronic hepatitis B.
AB  - BACKGROUND: Acute exacerbations (AE) of serum alanine aminotransferase activities
      that are 5 times above the normal upper limit frequently occur during the immune
      clearance phase of hepatitis Be antigen (HBeAg)-positive chronic hepatitis B
      (CHB). It is unclear how the varying clinical severities of AE reflect
      differences in the underlying immune responses against the hepatitis B virus.
      METHODS: We utilized magnetic bead-based purification methods coupled with MALDI
      TOF mass spectrometry to generate plasma peptide profiles from HBeAg-positive CHB
      patients experiencing AE without and with clinical decompensation. RESULTS:
      Hydrophobic interaction chromatography (HIC C18) provided a more discriminatory
      spectral profile than immobilized Cu(2+) metal ion affinity chromatography did
      for diagnosis of a clinical spectrum of AEs. Using the sorting algorithm, Support
      Vector Machine, a classification model consisting of 5 classifiers was determined
      to give a sensitivity of 94.7% and a specificity of 75% for differentiating
      patients with and without decompensation. Classifiers identified as fragments
      derived from transthyretin and apolipoprotein A-IV were significantly decreased
      and increased in patients with decompensation, respectively. CONCLUSIONS: Our
      study demonstrated that HIC C18 fractionation coupled with MALDI-TOF mass
      spectrometry can be used for differentiating AE with and without decompensation
      in patients with HBeAg-positive CHB.

PMID- 21867693
TI  - Protein kinase D1 mediates synergistic MMP-3 expression induced by TNF-alpha and
      bradykinin in human colonic myofibroblasts.
AB  - Stromal myofibroblasts regulate extracellular matrix components through the
      secretion of matrix metalloproteinases such as MMP-3. Both myofibroblasts and MMP
      3 have been implicated in colonic inflammation and cancer but the regulatory
      signaling mechanism(s) are unknown. Exposure of the human colonic myofibroblast
      cell line 18Co to TNF-alpha and bradykinin induced synergistic MMP-3 mRNA and
      protein expression, which were blocked by the preferential PKC inhibitors
      GF109203X and Go6983 and by the MEK inhibitor U0126. Transfection with siRNA
      targeting PKD1, a known downstream target of both bradykinin and PKC, completely
      inhibited MMP-3 mRNA and protein expression. Our results imply that TNF-alpha and
      bradykinin amplify MMP-3 expression at a transcriptional level through a
      signaling cascade involving PKC, PKD1, and MEK. PKD1 plays a critical role in the
      expression of MMP-3 in human colonic myofibroblasts, and may contribute to the
      pathophysiology underlying colitis-associated cancer.

PMID- 21867695
TI  - Effects of a single dose of oral iron on hepcidin concentrations in human urine
      and serum analyzed by a robust LC-MS/MS method.
AB  - BACKGROUND: The measurement of serum hepcidin, a peptide hormone that regulates
      iron metabolism, is clinically important to the understanding of iron homeostasis
      in health and disease. To date, the quantification of serum hepcidin levels by
      conventional immunological detection methods has proven problematic due to
      challenges in obtaining high quality antibodies which demonstrate good
      reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF) has been employed recently for more sensitive
      quantification of hepcidin; however, this method has high background levels and
      therefore less than optimal specificity. METHODS: In order to increase the
      specificity of the mass spectrometry based assay, we developed a robust, ultra
      performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol
      using multiple selected reaction monitoring (mSRM) for quantification of hepcidin
      levels in urine and serum of human subjects. With this assay, we assessed levels
      of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in
      ten adult human subjects without known disease. RESULTS: The linear response of
      hepcidin quantitation on each instrument was measured, and the correlation
      coefficients of these calibrations were r(2)=0.9512+/-0.0202 (n=5) for urine and
      r(2)=0.9709+/-0.0291 (n=5) for serum [r(2)=mean+/-SD]. Compared to baseline, the
      levels of urinary hepcidin between 2-4 h and 4-8 h of both women and men showed
      significant increases with p<0.05 and p<0.001, respectively. The levels of serum
      hepcidin between 4 h and 8 h in both women and men showed significant increases,
      compared with baseline values, with both p<0.01. Interestingly, we also observed
      some degree of oscillation of levels, occurring at later time points.
      CONCLUSIONS: We have developed and validated a new method for measuring hepcidin
      concentrations in human serum and urine and used it to demonstrate early
      increases with iron supplement in both urinary and serum levels of hepcidin,
      which return to baseline levels, except in urine samples from men.

PMID- 21867696
TI  - A metabolic profiling analysis of symptomatic gout in human serum and urine using
      high performance liquid chromatography-diode array detector technique.
AB  - BACKGROUND: Uric acid (UA) is the only biomedical indicator for gout in clinic
      that always leads to an uncertain diagnose. Due to the lack of reliable
      metabolites, it is now already highly desirable to diagnose gout definitely.
      METHODS: Metabonomics was employed to screen and identify novel biomarkers of
      gout based on human serum and urine. High performance liquid chromatography-diode
      array detector (HPLC-DAD) and orthogonal signal correction partial least squares
      discriminate analysis (OSC-PLS-DA) were also used for metabonomics study.
      RESULTS: Several potential biomarkers including uric acid, creatinine, tryptophan
      in serum and uric acid, creatinine, guanosine, hippuric acid in urine, were
      respectively screened and identified. For serum and urine, the predictive levels
      about the OSC-PLS-DA models of the gout and controls were 95.76% and 100%, and
      the correction levels about the seriousness of the disease were 90.32% and 87.5%,
      respectively. CONCLUSION: Compared with intermittent gout, the acute gout shows
      clearly the dysfunctions of purine, protein and glucose metabolism. The
      metabolizing of guanosine to UA increases the levels of UA in serum at the acute
      stage. Our research contributes to a better understanding of the metabolic
      mechanism and allowing the targeted therapy of gout at different stages.

PMID- 21867697
TI  - Morphine-induced antinociception in the rat: supra-additive interactions with
      imidazoline I2 receptor ligands.
AB  - Pain remains a significant clinical challenge and currently available analgesics
      are not adequate to meet clinical needs. Emerging evidence suggests the role of
      imidazoline I(2) receptors in pain modulation primarily from studies of the non
      selective imidazoline receptor ligand, agmatine. However, little is known of the
      generality of the effect to selective I(2) receptor ligands. This study examined
      the antinociceptive effects of two selective I(2) receptor ligands 2-BFI and
      BU224 (>2000-fold selectivity for I(2) receptors over alpha(2) adrenoceptors) in
      a hypertonic (5%) saline-induced writhing test and analyzed their interaction
      with morphine using a dose-addition analysis. Morphine, 2-BFI and BU224 but not
      agmatine produced a dose-dependent antinociceptive effect. Both composite
      additive curve analyses and isobolographical plots revealed a supra-additive
      interaction between morphine and 2-BFI or BU224, whereas the interaction between
      2-BFI and BU224 was additive. The antinociceptive effect of 2-BFI and BU224 was
      attenuated by the I(2) receptor antagonist/alpha(2) adrenoceptor antagonist
      idazoxan but not by the selective alpha(2) adrenoceptor antagonist yohimbine,
      suggesting an I(2) receptor-mediated mechanism. Agmatine enhanced the
      antinociceptive effect of morphine, 2-BFI and BU224 and the enhancement was
      prevented by yohimbine, suggesting that the effect was mediated by alpha(2)
      adrenoceptors. Taken together, these data represent the first report that
      selective I(2) receptor ligands have substantial antinociceptive activity and
      produce antinociceptive synergy with opioids in a rat model of acute pain. These
      data suggest that drugs acting on imidazoline I(2) receptors may be useful either
      alone or in combination with opioids for the treatment of pain.

PMID- 21867698
TI  - Focus on molecules: lens intrinsic membrane protein (LIM2/MP20).

PMID- 21867700
TI  - Dysfunction of the ubiquitin-proteasome system in the cerebellum of aging Ts65Dn
      mice.
AB  - In the cerebellum of adult-aging Ts65Dn mice, a murine model of Down syndrome,
      Purkinje cells undergo degeneration. Searching for the cause of Purkinje cell
      degeneration, we have studied the ubiquitin-proteasome system (UPS) in the
      cerebellum of aging Ts65Dn mice. Inhibition of UPS is sufficient to induce neuron
      degeneration and death. Proteasome chymotrypsin-like proteolytic activity was
      reduced by 35% in the cerebellum of Ts65Dn mice in comparison with euploid
      animals. Accordingly, Western blot analysis of ubiquitin showed an increase in
      ubiquitinated proteins. Immunocytochemistry for ubiquitin revealed strongly
      positive intranuclear inclusions in Purkinje cells and large neurons of
      cerebellar nuclei. The Western blot analysis of ubiquitin in nuclear protein
      extracts confirmed the increase of ubiquitinated proteins in the cell nuclei.
      After FUS immunocytochemistry, large intranuclear inclusions were visible in
      Purkinje cells and large neurons of cerebellar nuclei in Ts65Dn mice. Together,
      data indicate a possible role for proteasome inhibition in the cerebellar
      neurodegeneration in Ts65Dn mice.

PMID- 21867699
TI  - Immunocytochemical evidence of Tulp1-dependent outer segment protein transport
      pathways in photoreceptor cells.
AB  - Tulp1 is a protein of unknown function exclusive to rod and cone photoreceptor
      cells. Mutations in the gene cause autosomal recessive retinitis pigmentosa in
      humans and photoreceptor degeneration in mice. In tulp1-/- mice, rod and cone
      opsins are mislocalized, and rhodopsin-bearing extracellular vesicles accumulate
      around the inner segment, indicating that Tulp1 is involved in protein transport
      from the inner segment to the outer segment. To investigate this further, we
      sought to define which outer segment transport pathways are Tulp1-dependent. We
      used immunohistochemistry to examine the localization of outer segment proteins
      in tulp1-/- photoreceptors, prior to retinal degeneration. We also surveyed the
      condition of inner segment organelles and rhodopsin transport machinery proteins.
      Herein, we show that guanylate cyclase 1 and guanylate cyclase activating
      proteins 1 and 2 are mislocalized in the absence of Tulp1. Furthermore, arrestin
      does not translocate to the outer segment in response to light stimulation.
      Additionally, data from the tulp1-/- retina adds to the understanding of
      peripheral membrane protein transport, indicating that rhodopsin kinase and
      transducin do not co-transport in rhodopsin carrier vesicles and
      phosphodiesterase does not co-transport in guanylate cyclase carrier vesicles.
      These data implicate Tulp1 in the transport of selective integral membrane outer
      segment proteins and their associated proteins, specifically, the opsin and
      guanylate cyclase carrier pathways. The exact role of Tulp1 in outer segment
      protein transport remains elusive. However, without Tulp1, two rhodopsin
      transport machinery proteins exhibit abnormal distribution, Rab8 and Rab11,
      suggesting a role for Tulp1 in vesicular docking and fusion at the plasma
      membrane near the connecting cilium.

PMID- 21867701
TI  - Rehabilitative training following unilateral pyramidotomy in adult rats improves
      forelimb function in a non-task-specific way.
AB  - Spontaneous functional recovery following injury to the adult central nervous
      system can be enhanced with increased and focused activity, either through
      altered behaviour (skill learning, exercise or training) or by artificial
      stimulation (magnetic or electrical). In terms of training, the choice of
      paradigm plays a key role in the recovered behaviour. Here we show that task
      specific training leads to improved forelimb function that can be translated to a
      novel forelimb task. Adult Long-Evans rats received a unilateral pyramidotomy and
      we studied the effects of different post-lesion training paradigms for their
      ability to recover function in the impaired limb. We trained rats on either the
      single pellet grasping or the horizontal ladder task. Rats were tested on both
      tasks regardless of the training paradigm and also on a related, but novel
      forelimb task, the Staircase. Horizontal ladder training led to full recovery of
      this task, and also limited recovery on the familiar but untrained single pellet
      grasping task. In comparison, single pellet grasping training led to a smaller
      improvement on the horizontal ladder, but interestingly the same degree of
      recovery on the single pellet grasping task as horizontal ladder trained animals.
      Both training groups performed equally well on a novel, untrained forelimb
      grasping task. These results show that task-specific forelimb training can lead
      to functional recovery also in non-trained, complex, forelimb movements.
      Anatomically, only single pellet grasping training was associated with enhanced
      sprouting of the intact corticospinal tract across the cervical spinal cord
      midline to innervate the denervated side of the spinal cord.

PMID- 21867702
TI  - Bromocriptine methylate suppresses glial inflammation and moderates disease
      progression in a mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease
      characterized by a selective loss of upper and lower motor neurons. Since
      oxidative stress plays a crucial role in the progression of motor neuron loss
      observed in ALS, anti-oxidative agents could be an important therapeutic means
      for the ALS treatment. We have previously developed a drug screening system
      allowing the identification of small chemical compounds that upregulate
      endogenous neuronal apoptosis inhibitory protein (NAIP), an oxidative stress
      induced cell death suppressor. Using this system, we identified the dopamine D2
      receptor agonist bromocriptine (BRC) as one of NAIP-upregulating compounds. In
      this study, to prove the efficacy of BRC in ALS, we conducted a set of
      preclinical studies using a transgenic ALS mouse model carrying the H46R mutation
      in the human Cu/Zn superoxide dismutase (SOD1) gene ALS(SOD1(H46R)) by the post
      onset administration of BRC. ALS(SOD1(H46R)) mice receiving BRC showed sustained
      motor functions and modest prolonged survival after onset. Further, BRC treatment
      delayed anterior horn cell loss, and reduced the number of reactive astrocytes
      and the level of inflammatory factors such as inducible nitric oxide synthase
      (iNOS) and tumor necrosis factor (TNF)-alpha in the spinal cord of late
      symptomatic mice. In vitro study showed the reduced level of extracellular TNF
      alpha after lipopolysaccharide (LPS) exposure in BRC-treated mouse astrocytes.
      BRC-treated ALS(SOD1(H46R)) mice also showed a reduced level of oxidative damage
      in the spinal cord. Notably, BRC treatment resulted in an upregulation of anti
      oxidative stress genes, activating transcription factor 3 (ATF3) and heme
      oxygenase-1 (HO-1), and the generation of a glutathione (GSH) in SH-SY5Y cultured
      neuronal cells in a dopamine receptor-independent manner. These results imply
      that BRC protects motor neurons from the oxidative injury via suppression of
      astrogliosis in the spinal cord of ALS(SOD1(H46R)) mice. Thus, BRC might be a
      promising therapeutic agent for the treatment of ALS.

PMID- 21867703
TI  - Intrauterine growth restriction affects the maturation of myelin.
AB  - Intrauterine growth-restriction (IUGR) can lead to adverse neurodevelopmental
      sequelae in postnatal life. Our objective was to determine whether IUGR, induced
      by chronic placental insufficiency (CPI) in the guinea pig results in long-term
      deficits in brain myelination and could therefore contribute to altered neural
      function. CPI was induced by unilateral ligation of the uterine artery at mid
      gestation (term~67 days of gestation; dg), producing growth-restricted (GR)
      foetuses (60 dg), neonates (1 week) and young adults (8 week); controls were from
      the unligated horn or sham-operated animals. In GR foetuses (n=8) and neonates
      (n=7), white matter (WM) volume was reduced (p<0.05); this reduction did not
      persist in young adults (n=11) however the corpus callosum width was reduced
      (p<0.05). Immunoreactivity (IR) for myelin basic protein (MBP), myelin-associated
      glycoprotein (MAG) and myelin proteolipid protein (PLP), all markers of
      myelinating oligodendrocytes (OL), was reduced in GR foetuses compared to
      controls. MBP was the most markedly affected with an abnormal retention of
      protein in the OL soma and a reduction of its incorporation into the myelin
      sheath. MAG-IR OL density was reduced (p<0.05), while the density of OLs
      immunoreactive for Olig-2, a transcription factor expressed throughout the entire
      OL lineage, was increased (p<0.05). MBP-, MAG- and PLP-IR recovered to control
      levels postnatally. These results suggest that IUGR transiently delays OL
      maturation and myelination in utero but that myelination and WM volume are
      restored to control levels postnatally. Long-term deficits in myelination are
      therefore unlikely to be the major factor underlying the altered neurological
      function which can be associated with IUGR.

PMID- 21867704
TI  - Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin
      sensitive afferent nerves of rat urinary bladder.
AB  - Nitro-oleic acid (9- and 10-nitro-octadeca-9-enoic acid, OA-NO(2)) is an
      electrophilic fatty acid nitroalkene derivative that modulates gene transcription
      and protein function via post-translational protein modification. Nitro-fatty
      acids are generated from unsaturated fatty acids by oxidative inflammatory
      reactions and acidic conditions in the presence of nitric oxide or nitrite.
      Nitroalkenes react with nucleophiles such as cysteine and histidine in a variety
      of susceptible proteins including transient receptor potential (TRP) channels in
      sensory neurons of the dorsal root and nodose ganglia. The present study revealed
      that OA-NO(2) activates TRP channels on afferent nerve terminals in the urinary
      bladder and thereby increases bladder activity. The TRPV1 agonist capsaicin
      (CAPS, 1 MUM) and the TRPA1 agonist allyl isothiocyanate (AITC, 30 MUM), elicited
      excitatory effects in bladder strips, increasing basal tone and amplitude of
      phasic bladder contractions (PBC). OA-NO(2) mimicked these effects in a
      concentration-dependent manner (1 MUM-33 MUM). The TRPA1 antagonist HC3-030031
      (HC3, 30 MUM) and the TRPV1 antagonist diaryl piperazine analog (DPA, 1 MUM),
      reduced the effect of OA-NO(2) on phasic contraction amplitude and baseline tone.
      However, the non-selective TRP channel blocker, ruthenium red (30 MUM) was a more
      effective inhibitor, reducing the effects of OA-NO(2) on basal tone by 75% and
      the effects on phasic amplitude by 85%. In bladder strips from CAPS-treated rats,
      the effect of OA-NO(2) on phasic contraction amplitude was reduced by 65% and the
      effect on basal tone was reduced by 60%. Pretreatment of bladder strips with a
      combination of neurokinin receptor antagonists (NK1 selective antagonist, CP
      96345; NK2 selective antagonist, MEN 10,376; NK3 selective antagonist, SB
      234,375, 1 MUM each) reduced the effect of OA-NO(2) on basal tone, but not phasic
      contraction amplitude. These results indicate that nitroalkene fatty acid
      derivatives can activate TRP channels on CAPS-sensitive afferent nerve terminals,
      leading to increased bladder contractile activity. Nitrated fatty acids produced
      endogenously by the combination of fatty acids and oxides of nitrogen released
      from the urothelium and/or afferent nerves may play a role in modulating bladder
      activity.

PMID- 21867705
TI  - Functional changes in postsynaptic adenosine A(2A) receptors during early stages
      of a rat model of Huntington disease.
AB  - Huntington disease (HD) is a neurodegenerative disorder involving preferential
      loss of striatal GABAergic medium spiny neurons. Adenosine A(2A) receptors
      (A(2A)Rs) are present in the striatum at both presynaptic and post-synaptic
      levels. Blocking pre-synaptic A(2A)Rs, localized in glutamatergic terminals that
      contact striatal GABAergic dynorphinergic neurons, reduces glutamate release,
      which could be beneficial in HD. On the other hand, blockade of post-synaptic
      A(2A)Rs, localized in striatal GABAergic enkephalinergic neurons, could
      exacerbate the motor dysfunction. To evaluate the function of pre- or post
      synaptic A(2A)Rs in HD we used selective antagonists for these receptors in a
      transgenic rat model of HD. Locomotor activity after systemic administration of
      the postsynaptic A(2A)R antagonist KW-6002 was used to investigate the function
      of post-synaptic A(2A)Rs. The role of pre-synaptic A(2A)Rs was instead evaluated
      by measuring the reduction of the electromyographic response of mastication
      muscles during electrical stimulation of the orofacial motor cortex after the
      systemic administration of the presynaptic A(2A)R antagonist SCH-442416. The
      ability of KW-6002 to produce locomotor activation was lost at 6 and 12 month-old
      of age in heterozygous and homozygous transgenic rats, but not in wild-type
      littermates. Nevertheless, no significant changes were observed up to 12 months
      of age in the potency of SCH-442416 to decrease the electromyographic response
      after cortical electrical stimulation. These results agree with a selective
      impairment of the striatal GABAergic enkephalinergic neuronal function during pre
      symptomatic stages in HD. Since presynaptic A(2A)R function is not impaired, this
      receptor could probably be used as a target for the symptomatic treatment of the
      disease.

PMID- 21867706
TI  - The ubiquitin clan: A protein family essential for life.

PMID- 21867707
TI  - Influence of chronic HBV infection on pregnancy: a human model of maternofetal
      virus host interactions.

PMID- 21867708
TI  - PGE(2) induces oenocytoid cell lysis via a G protein-coupled receptor in the beet
      armyworm, Spodoptera exigua.
AB  - Eicosanoids mediate cellular and humoral immune responses in the beet armyworm,
      Spodoptera exigua, including activation of prophenoloxidase (PPO). PPO activation
      begins with release of its inactive zymogen, PPO, from oenocytoids in response to
      prostaglandins (PGs). Based on the biomedical literature, we hypothesized that
      PGs exert their actions via specific G protein-coupled receptor(s) in S. exigua.
      This study reports a G protein-coupled receptor (Se-hcPGGPCR1) gene, which is
      expressed in the hemocytes of S. exigua. The Se-hcPGGPCR1 consists of 420 amino
      acids and belongs to rhodopsin-type GPCRs. The high content of hydrophobic amino
      acid residues within the Se-hcPGGPCR1 protein is explained by prediction of seven
      transmembrane domains that are characteristic of these GPCRs. Except for the
      eggs, Se-hcPGGPCR1 was expressed in all life stages. During the larval stage, it
      was expressed in hemocytes and gut, but not in fat body nor in epidermis. Real
      time quantitative RT-PCR showed that bacterial challenge induced more than 20
      fold increases in its expression level. Fluorescence in situ hybridization showed
      that Se-hcPGGPCR1 was expressed in a specific hemocyte type, the oenocytoids. A
      specific eicosanoid, PGE(2), significantly induced oenocytoid lysis and increased
      PO activity in the plasma. In contrast, when Se-hcPGGPCR1 expression was
      suppressed by RNA interference (RNAi), the oenocytoid lysis and the PO activation
      in response to PGE(2) were not elevated above basal levels. A binding assay using
      intracellular calcium mobilization showed that the RNAi-treated hemocytes were
      significantly less responsive to PGE(2) than the control hemocytes. These results
      support our hypothesis with the specific finding that PGE(2) acts through Se
      hcPGGPCR1 to activate PPO by lysing oenocytoids.

PMID- 21867709
TI  - Taxa-specific heat shock proteins are over-expressed with crowding in the
      Australian plague locust.
AB  - Most heat shock proteins (Hsps) function as molecular chaperones that help
      organisms to cope with stress. Although the best empirical evidence is related to
      heat shock, there is evidence that Hsps and their encoding genes are involved in
      resistance to other ecologically relevant types of stresses such as those imposed
      by high population density. We quantified density-dependent gene expression of
      large (i.e. Hsp40, Hsc70 and Hsp90) and small (Hsp20.5, Hsp20.6 and Hsp20.7) heat
      shock genes in neural tissue of fifth-instar nymphs of the Australian plague
      locust, Chortoicetes terminifera, using reverse transcription-quantitative PCR.
      Locusts are of particular interest when studying the influence of stress induced
      by high population density since they show an extreme form of phenotypic
      plasticity changing from a cryptic solitarious phase to a swarming gregarious
      phase. Crowding led to a synchronous and sustained 2-3 fold increase in the
      expression of only two Hsp genes, Hsp20.5 and Hsp20.7, which do not BLAST with
      any known animal sequences and therefore are likely to be unique to members of
      the Orthoptera. This study opens a range of experiments to investigate the
      possibility of specific roles for these two small Hsps in the resistance to
      stressful conditions imposed by crowded environments and/or the expression of
      gregarious behavior as well as their evolutionary significance to locusts whose
      populations are regularly exposed to high density conditions in the field.

PMID- 21867710
TI  - Central projections of the wing afferents in the hawkmoth, Agrius convolvuli.
AB  - Flight behaviors in various insect species are closely correlated with their
      mechanical and neuronal properties. Compared to locusts and flies which have been
      intensively studied, moths have "intermediate" properties in terms of the
      neurogenic muscle activations, power generation by indirect muscles, and two
      winged-insect-like flapping behavior. Despite these unique characteristics,
      little is known about the neuronal mechanisms of flight control in moths. We
      investigated projections of the wing mechanosensory afferents in the central
      nervous system (CNS) of the hawkmoth, Agrius convolvuli, because the
      mechanosensory proprioceptive feedback has an essential role for flight control
      and would be presumably optimized for insect species. We conducted anterograde
      staining of nine afferent nerves from the fore- and hindwings. All of these
      afferents projected into the prothoracic, mesothoracic and metathoracic ganglia
      (TG1, 2 and 3) and had ascending fibers to the head ganglia. Prominent projection
      areas in the TG1-3 and suboesophageal ganglion (SOG) were common between the
      forewing, hindwing and contralateral forewing afferents, suggesting that
      information from different wings are converged at multiple levels presumably for
      coordinating wing flapping. On the other hand, differences of projections between
      the fore- and hindwing afferents were observed especially in projection areas of
      the tegulae in the TG1 and contralateral projections of the anterior forewing
      nerve in the TGs and SOG, which would reflect functional differences between
      corresponding mechanoreceptors on each wing. Afferents comprising groups of the
      campaniform sensilla at the wing bases had prominent ascending pathways to the
      SOG, resembling the head-neck motor system for gaze control in flies. Double
      staining of the wing afferents and flight or neck motoneurons also indicated
      potential connectivity between them. Our results suggest multiple roles of the
      wing proprioceptive feedback for flight and provide the anatomical basis for
      further understanding of neuronal mechanisms of the flight system in moths.

PMID- 21867711
TI  - Structural and functional characterization of an agonistic anti-human EphA2
      monoclonal antibody.
AB  - We report here the three-dimensional structure of human ephrin type A receptor 2
      (EphA2) bound to the Fab (fragment antigen binding) of an agonistic human
      antibody (1C1; IgG1/kappa). The structure of the corresponding complex was solved
      at a resolution of 2.5 A using molecular replacement and constitutes the first
      reported structure of a human ephrin receptor bound to an antibody. We have also
      defined the corresponding functional epitope using a mutagenesis-based approach.
      This study revealed discrete structural features that determine the fine
      specificity of 1C1 to EphA2. Our data also provided a molecular basis for 1C1
      mechanism of action. More precisely, we propose that its agonistic, internalizing
      properties are the result of ligand mimicry by the third heavy-chain
      complementarity-determining region of 1C1. Because EphA2 is an important
      contributor to cancer formation and progression, these findings may have
      implications for designing the next generation of anti-tumor therapies.

PMID- 21867712
TI  - Molecular determinants of self-association and rearrangement of a trimeric
      intermediate during the assembly of a parvovirus capsid.
AB  - The minute virus of mice (MVM) provides a simple model for the dissection of the
      molecular determinants of the self-assembly, stability, and dynamics of a
      biological supramolecular complex. MVM assembly involves the trimerization of
      capsid subunits in the cytoplasm; trimers are transported to the nucleus, where
      they suffer a conformational change and are made competent for capsid formation.
      Our previous study revealed that capsid assembly from trimers is dependent on
      stronger intertrimer interactions that are equally spaced in an equatorial belt
      surrounding each trimer. We have now targeted the interfaces between monomers
      within each trimer to identify the molecular determinants of trimerization and
      the rearrangement needed for capsid assembly. Twenty-eight amino acid residues
      per monomer were individually mutated to alanine to remove most of the stronger
      intersubunit interactions. The effects on trimer and capsid assembly and virus
      infectivity in cells were analyzed. No side chain was individually required for
      trimer assembly in the cytoplasm; in contrast, half of them were required to make
      the trimers competent for nuclear capsid assembly, even though none was close to
      intertrimer interfaces. These critical side chains are conserved and participate
      in extensive hydrophobic contacts, buried hydrogen bonds, or salt bridges between
      subunits. This study on MVM capsid assembly reveals that: (i) trimerization is a
      robust process, insensitive to removal of individual intersubunit interactions;
      and (ii) the rearrangement of the trimer intermediate required for capsid
      assembly is a global process that depends on the establishment of many
      interactions along the protein-protein interfaces within each trimer.

PMID- 21867714
TI  - Determining species tree topologies from clade probabilities under the
      coalescent.
AB  - One approach to estimating a species tree from a collection of gene trees is to
      first estimate probabilities of clades from the gene trees, and then to construct
      the species tree from the estimated clade probabilities. While a greedy consensus
      algorithm, which consecutively accepts the most probable clades compatible with
      previously accepted clades, can be used for this second stage, this method is
      known to be statistically inconsistent under the multispecies coalescent model.
      This raises the question of whether it is theoretically possible to reconstruct
      the species tree from known probabilities of clades on gene trees. We investigate
      clade probabilities arising from the multispecies coalescent model, with an eye
      toward identifying features of the species tree. Clades on gene trees with
      probability greater than 1/3 are shown to reflect clades on the species tree,
      while those with smaller probabilities may not. Linear invariants of clade
      probabilities are studied both computationally and theoretically, with certain
      linear invariants giving insight into the clade structure of the species tree.
      For species trees with generic edge lengths, these invariants can be used to
      identify the species tree topology. These theoretical results both confirm that
      clade probabilities contain full information on the species tree topology and
      suggest future directions of study for developing statistically consistent
      inference methods from clade frequencies on gene trees.

PMID- 21867715
TI  - Antiviral treatment for pandemic influenza: assessing potential repercussions
      using a seasonally forced SIR model.
AB  - When resources are limited, measures to control an incipient influenza pandemic
      must be carefully considered. Because several months are needed to mass-produce
      vaccines once a new pandemic strain has been identified, antiviral drugs are
      often considered the first line of defense in a pandemic situation. Here we use
      an SIR disease model with periodic transmission rate to assess the efficacy of
      control strategies via antiviral drug treatment during an outbreak of pandemic
      influenza. We show that in some situations, and independent of drug-resistance
      effects, antiviral treatment can have a detrimental impact on the final size of
      the pandemic. Antiviral treatment also has the potential to increase the size of
      the major peak of the pandemic, and cause it to occur earlier than it would have
      if treatment were not used. Our studies suggest that when a disease exhibits
      periodic patterns in transmission, decisions of public health policy will be
      particularly important as to how control measures such as drug treatment should
      be implemented, and to what end (i.e.; towards immediate control of a current
      epidemic peak, or towards potential delay and/or reduction of an anticipated
      autumn peak).

PMID- 21867716
TI  - Gestational and postpartum corticosterone exposure to the dam affects behavioral
      and endocrine outcome of the offspring in a sexually-dimorphic manner.
AB  - Exposure to high levels of glucocorticoids in utero and during the postpartum
      period has a detrimental effect on brain development. We created an animal model
      of postpartum stress/depression based on administering high levels of
      corticosterone (CORT) to the dams during the postpartum period which caused
      behavioral changes and reduced hippocampal cell proliferation in the offspring.
      As the consequences of early exposure to glucocorticoids may depend on the dose
      and the developmental stage of the offspring, the present study was conducted to
      investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given
      to dams either during gestation, postpartum or across both gestation and
      postpartum on the outcome of the offspring. Male and female offspring were
      weighed throughout the experiment, tested in a series of behavioral tests (forced
      swim test, open field, elevated plus maze) and basal and restraint stress CORT
      levels were examined in adolescence or young adulthood. Results show that
      maternal CORT exposure, regardless of when administered, significantly attenuated
      body weight gain until adulthood in the offspring. Offspring exposed to low
      maternal CORT, but not high maternal CORT, during the postpartum had higher basal
      levels of CORT as young adults. Further, male and female offspring of dams
      exposed to high maternal CORT in utero showed more depressive-like behavior in
      the forced swim test, while males of dams exposed to high maternal CORT
      postpartum exhibited more anxiety-like behavior in the elevated plus maze. Taken
      together, maternal glucocorticoid exposure have long lasting effects on male and
      female offspring's behavioral and neuroendocrine measures in adolescence and
      adulthood depending on the time of exposure to glucocorticoids. This article is
      part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21867717
TI  - Effect of cannabidiol on sleep disruption induced by the repeated combination
      tests consisting of open field and elevated plus-maze in rats.
AB  - Patients with post-traumatic stress disorder (PTSD) frequently complain of having
      sleep disturbances, such as insomnia and rapid eye movement (REM) sleep
      abnormality. Cannabidiol (CBD), a psycho-inactive constituent of marijuana,
      reduces physiological non-REM (NREM) sleep and REM sleep in normal rats, in
      addition to generating its anxiolytic effect. However, the effects of CBD on
      anxiety-induced sleep disturbances remain unclear. Because anxiety progression is
      caused by persistent stress for a period of time, we employed the repeated
      combination tests (RCT) consisting of a 50-min open field (OF) and a subsequent
      10-min elevated plus-maze (EPM) for four consecutive days to simulate the
      development of anxiety. Time spent in the centre arena of OF and during open arms
      of the EPM was substantially decreased in latter days of RCT, suggesting the
      habituation, which potentially lessens anxiety-mediated behavioural responses,
      was not observed in current tests. CBD microinjected into the central nucleus of
      amygdala (CeA) significantly enhanced time spent in centre arena of OF, increased
      time during the open arms and decreased frequency of entry to the enclosed arms
      of EPM, further confirming its anxiolytic effect. The decrease of NREM sleep
      during the first hour and the suppression of REM sleep during hours 4-10 after
      the RCT represent the similar clinical observations (e.g. insomnia and REM sleep
      interruption) in PTSD patients. CBD efficiently blocked anxiety-induced REM sleep
      suppression, but had little effect on the alteration of NREM sleep. Conclusively,
      CBD may block anxiety-induced REM sleep alteration via its anxiolytic effect,
      rather than via sleep regulation per se. This article is part of a Special Issue
      entitled 'Anxiety and Depression'.

PMID- 21867718
TI  - The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor
      potentiator LY 451646 are preserved in bdnf+/- heterozygous null mice.
AB  - Accumulating evidence suggests that biogenic amine-based antidepressants act, at
      least in part, via regulation of brain-derived neurotrophic factor (BDNF)
      signaling. Biogenic amine-based antidepressants increase BDNF synthesis and
      activate its signaling pathway through TrkB receptors. Moreover, the
      antidepressant-like effects of these molecules are abolished in BDNF deficient
      mice. Glutamate-based drugs, including the NMDA antagonist ketamine, and the AMPA
      receptor potentiator LY 451646, mimic the effects of antidepressants in
      preclinical tests with high predictive validity. In humans, a single intravenous
      dose of ketamine produces an antidepressant effect that is rapid, robust and
      persistent. In this study, we examined the role of BDNF in expression of the
      antidepressant-like effects of ketamine and an AMPA receptor potentiator (LY
      451646) in the forced swim test (FST). Ketamine and LY 451646 produced
      antidepressant-like effects in the FST in mice at 45 min after a single
      injection, but no effects were observed one week after a single ketamine
      injection. As previously reported, the effects of imipramine in the forced swim
      test were blunted in heterozygous BDNF knockout (bdnf(+/-)) mice. However
      ketamine and LY 451646 produced similar antidepressant-like responses in wildtype
      and bdnf(+/-) mice. Neither ketamine nor LY 451646 significantly influenced the
      levels BDNF or TrkB phosphorylation in the hippocampus when assessed at 45 min or
      7 days after the drug administration. These data demonstrate that under the
      conditions tested, neither ketamine nor the AMPA-potentiator LY 451656 activate
      BDNF signaling, but produce a characteristic antidepressant-like response in
      heterozygous bdnf(+/-) mice. These data indicate that unlike biogenic amine-based
      agents, BDNF signaling does not play a pivotal role in the antidepressant effects
      of glutamate-based compounds. This article is part of a Special Issue entitled
      'Anxiety and Depression'.

PMID- 21867719
TI  - Depressive-like behavior induced by tumor necrosis factor-alpha in mice.
AB  - Pro-inflammatory cytokines are implicated in the pathogenesis of depression.
      However, few animal models of cytokine-induced depression well characterized
      regarding its response to antidepressants are available. Hence, the aim of this
      study was to propose a model of depressive-like behavior induced by the
      administration of tumor necrosis factor-alpha (TNF-alpha) responsive to
      antidepressant treatments. TNF-alpha administered by i.c.v. route produced a
      depressive-like behavior in the forced swimming test (FST) and tail suspension
      test (TST) (0.1-1 fg/site and 0.001 fg/site, respectively), without altering the
      locomotor activity in the open-field test. In addition, anti-TNF-alpha antibody
      (0.1-1 pg/site, i.c.v.), but not the inhibitor of TNF-alpha synthesis thalidomide
      (3-30 mg/kg, s.c.) produced an antidepressant-like response in the FST. Moreover,
      either anti-TNF-alpha antibody (0.01 pg/site, i.c.v) or thalidomide (30 mg/kg,
      s.c.) reversed the depressive-like behavior induced by TNF- (0.1 fg/site, i.c.v.)
      in the FST. TNF-alpha receptor 1 (TNFR1) knockout mice exhibited an
      antidepressant-like behavior in the FST and in the TST as compared with the wild
      type mice. Treatment with fluoxetine (32 mg/kg, i.p), imipramine (15 mg/kg, i.p.)
      and desipramine (16 mg/kg, i.p) prevented the depressant-like effect induced by
      TNF-alpha (0.1 fg/site, i.c.v.) in the FST. In addition, TNF-alpha (0.1 fg/site,
      i.c.v.) administration produced an anhedonic response in a sucrose intake test,
      which was prevented by anti-TNF-alpha antibody (0.01 pg/site, i.c.v) or
      fluoxetine (32 mg/kg, i.p). Taken together, these results indicate that TNF-alpha
      produces a depressive-like state in mice, reinforcing the notion that an
      inflammatory component may play an important role in the pathophysiology of
      depression and suggesting that the central administration of TNF-alpha may be a
      novel approach to study the inflammatory component of depressive disorder. This
      article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21867721
TI  - Facile radiosynthesis of new carbon-11-labeled propanamide derivatives as
      selective androgen receptor modulator (SARM) radioligands for prostate cancer
      imaging.
AB  - The androgen receptor (AR) is an attractive target for the treatment and
      molecular imaging of prostate cancer. New carbon-11-labeled propanamide
      derivatives were first designed and synthesized as selective androgen receptor
      modulator (SARM) radioligands for prostate cancer imaging using the biomedical
      imaging technique positron emission tomography (PET). The target tracers, (S)-N
      (4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[(11)C]methoxyphenoxy)-2
      methylpropanamide ([(11)C]8a), (S)-2-hydroxy-3-(2-[(11)C]methoxyphenoxy)-2-methyl
      N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([(11)C]8 e), (S)-N-(4-cyano-3
      (trifluoromethyl)phenyl)-2-hydroxy-3-(4-[(11)C]methoxyphenoxy)-2
      methylpropanamide ([(11)C]8c) and (S)-2-hydroxy-3-(4-[(11)C]methoxyphenoxy)-2
      methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([(11)C]8 g), were
      prepared by O-[(11)C]methylation of their corresponding precursors, (S)-N-(4
      cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-hydroxyphenoxy)-2
      methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methyl-N-(4-nitro-3
      (trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3
      (trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methylpropanamide (9 c)
      and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4-nitro-3
      (trifluoromethyl)phenyl)propanamide (9 d), with [(11)C]CH(3)OTf under basic
      conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method
      in 55 +/- 5% (n = 5) radiochemical yields based on [(11)C]CO(2) and decay
      corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23
      min, the radiochemical purity was >99%, and the specific activity at end of
      synthesis (EOS) was 277.5 +/- 92.5 GBq/MUmol (n = 5).

PMID- 21867720
TI  - Measures of anxiety, amygdala volumes, and hippocampal scopolamine phMRI response
      in elderly female rhesus macaques.
AB  - In nonhuman primates, anxiety levels are typically assessed by observing social
      hierarchies or behavior in an intruder task. As measures of anxiety might
      influence performance on a particular cognitive task, it is important to analyze
      these measures in the same room as used for the cognitive task. As we use a
      playroom for the spatial maze test, we classified elderly female rhesus macaques
      (Macaca mulatta) monkeys, as bold or reserved monkeys based on the time spent in
      specific areas of this room. Based on their exploratory behavior in the playroom,
      bold monkeys were defined as animals that spent 20% more time in the unprotected
      areas of the room than in the protected areas, whereas reserved monkeys spent a
      comparable amount of time in both areas. MRI analyses showed that reserved
      monkeys had a smaller amygdala compared to bold monkeys but there were no group
      differences in hippocampal volumes. In addition, the amount of time spent in the
      corners of the room was negatively correlated with the right amygdala as well as
      the total amygdala size. Finally, reserved monkeys showed a lower phMRI response
      to the muscarinic receptor antagonist scopolamine compared to the bold monkeys.
      Thus, in elderly female nonhuman primates measures of anxiety are associated with
      structural amygdala differences and hippocampal muscarinic receptor function.
      This article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21867722
TI  - Recurrent and synchronous insect pest outbreaks in forests.
AB  - A minimal model for the interactions of trees, insects, and their enemies
      suggests a simple formula for splitting all forests where insect outbreaks can
      occur into two categories: where outbreaks are periodic and endogenously
      generated and where outbreaks are triggered by exogenous factors and are, in
      general, recurrent but aperiodic. The formula is in full agreement with all field
      studies in which various phenomena triggering insect outbreaks have been
      identified. The observed consequences of introductions and removals of insects
      are also well predicted by the minimal model. But, even more surprisingly, the
      model allows a simple and explicit condition for the synchronization of outbreaks
      in spatially extended forests to be derived analytically. This condition is, in
      general, satisfied when the insect is a so-called pest, that is, when the
      outbreaks are extreme. The model also predicts the possibility of traveling waves
      of insect outbreaks.

PMID- 21867723
TI  - Cylindrospermopsin induced DNA damage and alteration in the expression of genes
      involved in the response to DNA damage, apoptosis and oxidative stress.
AB  - Cylindrospermopsin (CYN), a potent cyanobacterial cytototoxin produced by certain
      freshwater cyanobacteria, is regularly found in water supplies in many parts of
      the world, and has been associated with the intoxication of humans and livestock.
      The few genotoxicity studies available indicate that CYN is genotoxic, generally
      implying that it is pro-genotoxic. In human peripheral blood lymphocytes (HPBLs)
      CYN (0, 0.05, 0.1 and 0.5 MUg/ml) induced the formation of DNA single strand
      breaks, applying the comet assay. Time and dose dependent significant increase in
      the frequency of micronuclei and nuclear buds was observed after the exposure of
      HPBLs to CYN, while there was only slight increase in the number of nucleoplasmic
      bridges. For the first time the modulation of gene expression in HPBLs was
      studied after the exposure to CYN (0.5 MUg/ml), using the quantitative real-time
      PCR. The genes presumably involved in CYN metabolism (CYP1A1 and CYP1A2) were up
      regulated after the exposure. CYN induced changes in the mRNA expression of P53
      and its downstream regulated DNA damage responsive genes MDM2, GADD45alpha and
      apoptosis genes, BCL-2 and BAX, as well as oxidative stress responsive genes
      (GPX1, SOD1, GSR, GCLC), while no changes in the expression of genes CDKN1A and
      CAT were observed. These results provide strong evidence that CYN should be
      considered as genotoxic and that lymphocytes can also be a target of
      cylindrospermopsin induced genotoxicity.

PMID- 21867725
TI  - Inflammatory effects of the toxic cyanobacterium Geitlerinema amphibium.
AB  - Toxic cyanobacteria in public water reservoirs may cause severe health issues for
      livestock and human beings. Geitlerinema amphibium, which is frequently found in
      Sao Paulo City's drinking water supplies, showed toxicity in the standard mouse
      bioassay, while displaying signs of intoxication and post-mortem findings
      different from those showed by animals intoxicated by known cyanotoxins. We
      report here the alterations caused by G. amphibium methanolic extract on mouse
      microcirculatory network, as seen by in vivo intravital microscopy, besides
      observations on leukocyte migration, cytokine quantitation, and results of
      toxicological essays. Our data showed that G. amphibium methanolic extract
      displayed time- and dose-dependent pro-inflammatory activity, and that at lower
      doses [125 and 250 mg/kg body weight (b.w.)] increased the leukocyte rolling,
      caused partial venular stasis, as well as induced an increase in leukocyte counts
      in the peripheral blood and peritoneal washings. At higher doses (500 and 1000
      mg/kg b.w.), the extract caused ischemic injury leading to animal death. As
      confirmed by mass spectrometric studies and polymyxin B test, the G. amphibium
      methanolic extract did not contain lipopolysaccharides.

PMID- 21867726
TI  - Uncoupled binding and folding of immune signaling-related intrinsically
      disordered proteins.
AB  - The classical protein structure-function paradigm has been challenged by the
      emergence of intrinsically disordered proteins (IDPs), the proteins that do not
      adopt well-defined three-dimensional structures under physiological conditions.
      This development was accompanied by the introduction of a "coupled binding and
      folding" paradigm that suggests folding of IDPs upon binding to their partners.
      However, our recent studies challenge this general view by revealing a novel,
      previously unrecognized phenomenon - uncoupled binding and folding. This
      biologically important mechanism is characteristic of members of a new family of
      IDPs involved in immune signaling and underlies their unusual properties
      including: (1) specific homodimerization, (2) the lack of folding upon binding to
      a well-folded protein, another IDP molecule, or to lipid bilayer membranes, and
      (3) the "scissors-cut paradox". The third phenomenon occurs in diverse IDP
      interactions and suggests that properties of IDP fragments are not necessarily
      additive in the context of the entire protein. The "no disorder-to-order
      transition" type of binding is distinct from known IDP interactions and is
      characterized by an unprecedented observation of the lack of chemical shift and
      peak intensity changes in multidimensional NMR spectra, a fingerprint of
      proteins, upon complex formation. Here, I focus on those interactions of IDPs
      with diverse biological partners where the binding phase driven by electrostatic
      interactions is not be necessarily followed by the hydrophobic folding phase. I
      also review new multidisciplinary knowledge about immune signaling-related IDPs
      and show how it expands our understanding of cell function with multiple
      applications in biology and medicine.

PMID- 21867724
TI  - Development of a sea anemone toxin as an immunomodulator for therapy of
      autoimmune diseases.
AB  - Electrophysiological and pharmacological studies coupled with molecular
      identification have revealed a unique network of ion channels--Kv1.3, KCa3.1,
      CRAC (Orai1 + Stim1), TRPM7, Cl(swell)--in lymphocytes that initiates and
      maintains the calcium signaling cascade required for activation. The expression
      pattern of these channels changes during lymphocyte activation and
      differentiation, allowing the functional network to adapt during an immune
      response. The Kv1.3 channel is of interest because it plays a critical role in
      subsets of T and B lymphocytes implicated in autoimmune disorders. The ShK toxin
      from the sea anemone Stichodactyla helianthus is a potent blocker of Kv1.3. ShK
      186, a synthetic analog of ShK, is being developed as a therapeutic for
      autoimmune diseases, and is scheduled to begin first-in-man phase-1 trials in
      2011. This review describes the journey that has led to the development of ShK
      186.

PMID- 21867727
TI  - Motor and locomotor responses to systemic amphetamine in three lines of
      selectively bred Long-Evans rats.
AB  - The goal of the study was to measure spontaneous and amphetamine-induced motor
      and locomotor activity in three selectively bred lines of male Long-Evans rats.
      The number of 50 kHz ultrasonic vocalizations (USVs) emitted in response to
      heterospecific play with human hand ("tickling") had been measured daily in these
      lines of rats from 21 to 24 days of age, as a criterion for dividing them into
      high vocalizing line, low vocalizing line, and random breeding and testing lines.
      This study sought to determine whether selection of rats based on their affective
      social-vocalizations also had effects on their locomotor performance and
      sensitivity to amphetamine. In this study adult animals from the 25th generation
      (with no further selection) were tested. The results showed that rats, which were
      selectively bred to emit high numbers of 50 kHz vocalizations, also exhibited
      elevated levels of spontaneous locomotor activity. After systemic injection of d
      amphetamine (1.5mg/kg), the level of motor and locomotor activity significantly
      increased further in all the lines as compared to saline controls. The horizontal
      and vertical activities and the distance covered by rats of the high line, both
      at the baseline and after amphetamine challenge, were significantly higher than
      those of the low line animals in absolute scores but not as proportion of
      relevant saline controls. Since appetitive 50 kHz USVs and locomotor activity are
      both dependent on the activity of the dopamine system, it is concluded that
      selection of rats based on the expression of their positive emotional state is
      also selecting other features than vocalization, namely locomotor behavior. This
      may help explain why these animals are relatively resistant to depressogenic
      manipulations.

PMID- 21867728
TI  - Adverse renal outcomes associated with antibiotic-laden spacers in two-stage
      joint revisions.

PMID- 21867729
TI  - Occupational risk for cytomegalovirus, but not for parvovirus B19 in child-care
      personnel in France.
AB  - BACKGROUND: Studies assessing the risk of cytomegalovirus (CMV), parvovirus B19
      (B19V), rubella and varicella infections in female child-care personnel may help
      define appropriate preventive strategies during pregnancy. METHODS: Serologic
      testing for all four viruses and a self-administered questionnaire to identify
      risk factors were conducted on child-care staff aged 20-50 years old and on a
      reference group of women. RESULTS: In 395 exposed and 382 reference women, CMV,
      B19V, rubella and varicella seroprevalence were 69.4, 79.4, 98.7, 100% for
      exposed women, and 41.1, 68.0, 98.2, 99.7% for reference women, respectively. For
      CMV, the adjusted seroprevalence ratio (PR) of exposed versus reference workers,
      (PR, 1.43 [95% IC, 1.22-1.69]) was observed as of the first year of exposure. The
      risk attributed to occupation was 30.1%. Identified risk factors included
      exposure duration, past employment in maternity hospital, and participation in
      cleaning tasks. The risk attributable to personal factors ranged from 14.5% to
      32.4%. The adjusted B19V PR was not significant (PR, 1.05 [95% IC, 0.94-1.16]).
      CONCLUSIONS: French female child-care staff runs an occupational risk for CMV
      infection, but not for B19V infection. The fraction attributable to this CMV
      occupational risk was not higher than the risk associated with personal factors.

PMID- 21867731
TI  - Use of plethysmography in assessing the efficacy of antivirals in a mouse model
      of pandemic influenza A virus.
AB  - The recently emerged swine-origin H1N1 influenza A virus (IAV) caused a pandemic
      outbreak in 2009 with higher risk of severe disease among children and pregnant
      women in their third trimester (Van Kerkhove et al., 2011), and is continuing to
      be important seasonal IAV strain. Mice are commonly used in antiviral studies as
      models of influenza disease, which utilize morbidity and mortality to assess the
      efficacy of a test compound. Here, we investigated the utility of unrestrained
      plethysomography to quantify the lung function of IAV-infected BALB/c mice.
      Administration of a lethal dose (~30X LD(50)) of pandemic H1N1 IAV resulted in a
      rapid decline in breath volume, as determined by a significant (P<0.001) decrease
      in the pressure associated with inspiration and expiration detected as early as 2
      days after virus challenge. Severe disease was also accompanied by a significant
      (P<0.05) increase in breath time on 8 dpi. Plethysmography parameters correlated
      with weight loss and other parameters of disease such as gross pathology and the
      weight of the lung. Breath time was reduced in surviving mice challenged with a
      sublethal dose of virus as compared with normal controls, and is a predictive
      indicator of outcome in these mice. In antiviral studies, the use of
      plethysmography resulted in the detection of a clear and rapid treatment
      response, which was similar to other non-invasive parameters, such as weight
      change. Oseltamivir and ribavirin significantly (P<0.001) improved parameters of
      lung function, particularly mean breath volume, as early as 2 dpi and in a dose
      dependent manner. Moreover, a combination of these two drugs further improved
      these parameters. Plethysmography provides a sensitive evaluation of lung
      function in IAV-infected mice in response to antiviral therapy.

PMID- 21867732
TI  - In vitro inhibitory effect of carrageenan oligosaccharide on influenza A H1N1
      virus.
AB  - Carrageenan polysaccharide has been reported to be able to inhibit the infection
      and replication of many different kinds of viruses. Here, we demonstrated that a
      2 kDa kappa-carrageenan oligosaccharide (CO-1) derived from the carrageenan
      polysaccharide, effectively inhibited influenza A (H1N1) virus replication in
      MDCK cells (selectivity index >25.0). Moreover, the 2 kDa CO-1 inhibited
      influenza A virus (IAV) replication better than that of 3 kDa and 5 kDa kappa
      carrageenan oligosaccharides (CO-2 and CO-3). IAV multiplication was suppressed
      by carrageenan oligosaccharide treatment in a dose-dependent manner. Carrageenan
      oligosaccharide CO-1 did not bind to the cell surface of MDCK cells but
      inactivated virus particles after pretreatment. Different to the actions of
      carrageenan polysaccharide, CO-1 could enter into MDCK cells and did not
      interfere with IAV adsorption. CO-1 also inhibited IAV mRNA and protein
      expression after its internalization into cells. Moreover, carrageenan
      oligosaccharide CO-1 had an antiviral effect on IAV replication subsequent to
      viral internalization but prior to virus release in one replication cycle.
      Therefore, inhibition of IAV intracellular replication by carrageenan
      oligosaccharide might be an alternative approach for anti-influenza A virus
      therapy.

PMID- 21867730
TI  - Novel pharmacological targets for the rhythm control management of atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is a growing clinical problem associated with increased
      morbidity and mortality. Development of safe and effective pharmacological
      treatments for AF is one of the greatest unmet medical needs facing our society.
      In spite of significant progress in non-pharmacological AF treatments (largely
      due to the use of catheter ablation techniques), anti-arrhythmic agents (AADs)
      remain first line therapy for rhythm control management of AF for most AF
      patients. When considering efficacy, safety and tolerability, currently available
      AADs for rhythm control of AF are less than optimal. Ion channel inhibition
      remains the principal strategy for termination of AF and prevention of its
      recurrence. Practical clinical experience indicates that multi-ion channel
      blockers are generally more optimal for rhythm control of AF compared to ion
      channel-selective blockers. Recent studies suggest that atrial-selective sodium
      channel block can lead to safe and effective suppression of AF and that
      concurrent inhibition of potassium ion channels may potentiate this effect. An
      important limitation of the ion channel block approach for AF treatment is that
      non-electrical factors (largely structural remodeling) may importantly determine
      the generation of AF, so that "upstream therapy", aimed at preventing or
      reversing structural remodeling, may be required for effective rhythm control
      management. This review focuses on novel pharmacological targets for the rhythm
      control management of AF.

PMID- 21867733
TI  - Comparative antiviral activity of integrase inhibitors in human monocyte-derived
      macrophages and lymphocytes.
AB  - The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810,
      IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166
      lymphocytic T cells, in order to determine their relative potency and efficacy in
      different cellular systems of HIV infection. Raltegravir showed better protective
      efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1
      activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an
      inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV
      1 compound in all cellular systems. All effective integrase inhibitors exhibited
      a potent antiviral activity against both X4 and R5 HIV-1 strains. In general,
      raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or
      slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048,
      the EC(50) was 0.4, 0.9, 11.5 nM in macrophages, in PBMCs and T cells,
      respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6 nM, respectively;
      for IN5 the EC(50) was 0.5, 13.7, and 5.7 nM, respectively.

PMID- 21867734
TI  - Early electrophysiological indicators for predictive processing in audition: a
      review.
AB  - The auditory system essentially deals with sequential type of input and thus
      requires processing that is particularly suited to extract stimulus relations
      within a sequence. Evidence from a variety of paradigms converges to show that
      the auditory system automatically uses stimulus predictability for facilitating
      its sequential processing. This type of predictive processing does not require
      attentional processing of the sounds or cognitive control of the predictions, nor
      does it involve the preparation of motor responses to the auditory stimuli. We
      will present a taxonomy of paradigms and resulting electrophysiological
      indicators for such automatic predictive processing in terms of event-related
      potential components and oscillatory activity. These indicators will include
      signals of fulfilled predictions (match signals such as N1 attenuation,
      repetition positivity, and early evoked gamma band response enhancement) as well
      as signals of violated predictions (mismatch signals such as the mismatch
      negativity and stimulus omission responses). We will show how recent approaches
      have revealed particularly early indicators of predictive processing down to the
      level of the auditory middle-latency responses. We will discuss the strength of
      the various indicators in terms of a truly predictive account of auditory
      processing (as opposed to, e.g., a retrospective verification of predictions).
      Finally, we will discuss the benefits of a predictive system within and beyond
      auditory processing. In conclusion, we argue in favor of the overwhelming
      evidence for predictions in audition, flexibly instantiated on different levels
      and timescales, and we aim to provide guidance along a variety of research
      paradigms illustrating the existence of these predictions.

PMID- 21867735
TI  - Efficient skin permeation of soluble proteins via flexible and functional nano
      carrier.
AB  - In spite of several intrinsic and distinct advantages, a topical and transdermal
      administration of drugs has been limited mainly due to very low permeability of
      drugs across skin. Especially, it is generally regarded that hydrophilic
      macromolecules such as proteins, peptides, and vaccines cannot penetrate across
      skin. In this study, we demonstrated that chitosan-conjugated, Pluronic-based
      nano-carrier (nanogel) can act as an efficient delivery vehicle of hydrophilic
      proteins across human skin. The functional nano-carrier (<100 nm in size),
      chemically-crosslinking Pluronic F 127 with chitosan conjugation, is flexible and
      soft with reservoir characteristics for biomacromolecules. The in-vitro
      permeation experiments through human cadaver skin revealed remarkable
      permeability of hydrophilic proteins of various sizes including FITC-BSA (67 kDa)
      and FITC-Insulin (6 kDa) by direct penetration of the nano-carrier across skin.
      The bioactivity post-permeation of proteins via the functional nano-carrier was
      also confirmed by delivering beta-galactosidase. Results presented in this paper
      suggest the use of chitosan-conjugated flexible nano-carrier as a novel platform
      for transcutaneous delivery of hydrophilic macromolecules and other drug-delivery
      applications.

PMID- 21867736
TI  - Graphene-based hybrid materials and devices for biosensing.
AB  - Graphene's unique properties have made it a popular candidate for nanomaterial
      based biosensors. Its remarkable characteristics have led to its rapid
      development in the electrochemical biosensing, field effect transistors, and
      optical biosensing as well as the creation graphene-metal nanoparticle hybrids
      for improved performance. This article comprehensively reviews the most recent
      trends in graphene-based biosensors and attempts to identify the future
      directions in which the field is likely to thrive.

PMID- 21867737
TI  - Delayed ischemic postconditioning protects hippocampal CA1 neurons by preserving
      mitochondrial integrity via Akt/GSK3beta signaling.
AB  - Delayed ischemic postconditioning (Post C), which involves a brief ischemia
      followed by reperfusion 2 days after 8-10min global cerebral ischemia (GCI), has
      been shown to exert a remarkable protection of the vulnerable hippocampal CA1
      region of the brain and attenuation of behavioral deficits, although the
      mechanisms remain poorly understood. The purpose of the current study was to
      explore the effect of Post C upon mitochondrial integrity, cytochrome c release
      and Bax translocation as a potential key mechanism for Post C protection of the
      critical hippocampal CA1 region neurons. The results of the study revealed that
      ischemic Post C (3min) administered 2 days after 8-min GCI exerted a robust
      preservation from GCI injury, as evidenced by the increase of NeuN-positive and
      the decrease of TUNEL-positive cells, as well as morphological features of
      mitochondrial integrity in the hippocampal CA1 region. We also found that Post C
      significantly blocked inner mitochondrial membrane potential depolarization, as
      shown by JC-1 staining, and attenuates cytochrome c release and Bax translocation
      induced by GCI. Pre-treatment of the PI3K inhibitor LY294002, 20min prior to Post
      C, significantly attenuated Post C-induced elevation of p-Akt and p-GSK3beta, as
      well as prevented Post C enhancement of mitochondrial integrity and Post C
      neuroprotection. The results suggest that phosphorylation of Akt and subsequent
      inactivation of GSK3beta signaling is critical in mediating Post C beneficial
      effects upon mitochondrial integrity, function and neuroprotection following GCI
      injury.

PMID- 21867738
TI  - Comparison of KIR gene content profiles revealed a difference between northern
      and southern Persians in the distribution of KIR2DS5 and its linked loci.
AB  - Killer cell immunoglobulin-like receptors (KIR) are the key receptors of human
      natural killer (NK) cells that mount an early immune response against infection
      and tumors. The number and type of KIR genes are substantially variable between
      individuals and populations. Recently we reported KIR gene content diversity in a
      Persian population living in the southern province of Fars, which is comparable
      to that of European Caucasians. These results are consistent with the ethnic
      ancestry and affinity between Persians and Caucasians. Herein we analyzed another
      Persian population living in the northern province of Tehran and discovered an
      unexpected increase in the distribution of KIR2DS5 and its linked loci KIR3DS1, 
      2DS1, and -2DL5 in northern Persians compared with that reported in the southern
      Persian population. Although the geographic barriers may have limited the gene
      flow, the impact of the local environment on the natural selection of KIR2DS5 and
      its linked loci in the northern Persians cannot be completely ruled out. The
      difference in northern and southern populations in activating KIR gene content
      creates an appealing hypothesis that KIR2DS5-enriched northern Persians are more
      resistant to developing clinical conditions demonstrated to be associated with
      KIR2DS5, such as psoriasis vulgaris, endometriosis, ankylosing spondylitis, and
      acute rejection of kidney grafts, compared with those living in the southern part
      of the country.

PMID- 21867739
TI  - Surface molecules on stimulated plasmacytoid dendritic cells are sufficient to
      cross-activate resting myeloid dendritic cells.
AB  - Human plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs) are
      2 types of antigen-presenting cells that exert complementary roles in innate
      immune responses. We demonstrated previously that in the presence of suboptimal
      stimulation or when only 1 dendritic cell type is directly stimulated, contact
      dependent crosstalk between mDCs and pDCs leads to the activation of both cell
      types and thus provides them with the ability to induce an optimal T-cell
      response. The precise mechanism is currently unknown. Here we demonstrate that
      pDCs, unable to secrete soluble factors because of previous stimulation, induce
      optimal mDC maturation, indicating that resting immature mDCs are fully competent
      to respond to Toll-like receptor-9-engaged pDCs in the absence of soluble
      factors. Thus, we conclude that immature mDCs already express receptors
      recognized by ligands that are upregulated on the surface of activated pDCs.
      Intercellular adhesion molecule-1 upregulated by activated pDCs may play a role
      in a donor-dependent manner.

PMID- 21867740
TI  - Melamine impairs spatial cognition and hippocampal synaptic plasticity by
      presynaptic inhibition of glutamatergic transmission in infant rats.
AB  - The scandal of melamine-contamination has not been quite blown out, since the
      toxicity of melamine continues to raise concerns for public health. It has been
      well known that fetus and infant periods play the most important roles in brain
      development, whereas little has been done on the harmful effects of melamine on
      the center nervous system (CNS) of children. In the present study, we
      investigated the effects of melamine on behavioral and electrophysiology
      alternations in rats, and the effects of melamine on synaptic transmission were
      examined using whole-cell patch-clamp technique in the hippocampal CA1 neurons of
      infant rats. Morris water maze (MWM) test showed that learning and memory
      abilities were impaired significantly by melamine. The long-time potentiation
      (LTP) test exhibited that the field excitatory postsynaptic potential (fEPSP)
      slopes were significantly lower in melamine group compared to that in control
      group. Furthermore, the data of whole-cell patch-clamp experiments showed that
      melamine decreased the frequencies of both spontaneous EPSCs (sEPSCs) and
      minitura EPSCs (mEPSCs) to the same extent (about 76% and 78% respectively).
      However, there were no significant changes in sEPSC or mEPSC amplitude or
      kinetics after melamine addition, indicating that the effect of melamine on
      glutamatergic transmission was probably presynaptic. In conclusion, melamine
      reduced the release of glutamate in presynaptic transmission of hippocampus,
      which partly resulted in diminished LTP and further damaged the function of
      learning and memory.

PMID- 21867741
TI  - Vasopressin controls stanniocalcin-1 gene expression in rat and mouse kidney.
AB  - Renal stanniocalcin-1 (STC-1) is made by collecting duct principal cells for
      autocrine and paracrine targeting of the distal nephron. While the underlying
      purpose of this targeting is poorly understood, increased targeting is tied to
      changes in extracellular fluid (ECF) balance. For example, water deprivation is a
      potent stimulator of renal STC-1 gene activity in both rats and mice. The effects
      are most evident in cortical kidney where transcript levels are increased as much
      as 8-fold, as compared to 2-fold in the papilla. As is now known, this gene
      upregulation occurs in response to the dual consequences of water deprivation;
      hypertonicity followed by hypovolemia. The cortical gene has proven to be
      uniquely responsive to hypertonicity and that in papilla to hypovolemia; the
      implication being that STC-1 has different roles in the two zones, both of which
      are somehow related to ECF balance. The role of arginine vasopressin (AVP) in
      maintaining ECF balance is well established. Moreover, hypertonicity and
      hypovolemia are, respectively, the primary and secondary stimulators of AVP
      release. Therefore the present study explored the hypothesis that AVP was
      responsible for inducing the STC-1 gene in one or both zones. The results showed
      that this was indeed the case. AVP had time and dose-dependent stimulatory
      effects on the gene in both rat and mouse cortical kidney. In the papilla,
      however, gene regulation was more complex, as AVP was inhibitory in rats but
      stimulatory in mice. Further studies on papilla revealed that angiotensin II (ANG
      II) was stimulatory in rats, but inhibitory in mice. Moreover, ANG II attenuated
      the stimulatory effects of AVP in mouse cortex and papilla. Receptor agonist
      studies revealed that the effects of AVP in both zones were mediated exclusively
      through the V2 receptor (V1a, V1b and oxytocin-specific agonists had no effect).
      The findings serve to further implicate STC-1 in the renal control of ECF
      balance.

PMID- 21867742
TI  - Chromosome 10 and RET gene copy number alterations in hereditary and sporadic
      Medullary Thyroid Carcinoma.
AB  - About 30% of hereditary Medullary Thyroid Carcinoma (MTC) have been demonstrated
      to harbour imbalance between mutant and wild-type RET alleles. We studied the RET
      copy number alterations (RET CNA) in 65 MTC and their correlation with RET
      mutation and patients' outcome. Fluorescence in situ Hybridization and Real-time
      PCR revealed RET CNA in 27.7% MTC but only in a variable percentage of cells. In
      sporadic MTC, RET CNA were represented by chromosome 10 aneuploidy while in
      hereditary MTC by RET amplification. A significant higher prevalence of RET CNA
      was observed in RET mutated MTC (P=0.003). RET CNA was also associated to a
      poorer outcome (P=0.005). However, the multivariate analysis revealed that only
      RET mutation and advanced clinical stage correlated with the worst outcome. In
      conclusion, 30% MTC harbour RET CNA in variable percentage of cells suggesting
      cell heterogeneity. RET CNA can be considered a poor prognostic factor
      potentiating the poor prognostic role of RET mutation.

PMID- 21867743
TI  - Exploratory behavior during stance persists with visual feedback.
AB  - Recent evidence showing center of pressure (COP) displacements increase following
      an external stabilization of the center of mass (COM) supports the theory that
      postural sway may be exploratory and serve as a means of acquiring sensory
      information. The aim of the current study was to further test this theory and
      rule out potential confounding effects of sensory illusions or motor drift on
      prior observations. Participants stood as still as possible in an apparatus which
      allowed movements of the COM to be stabilized ("locked") without subject
      awareness, and they were provided real-time visual feedback of their COM or COP
      throughout the trial. If there was an influence of sensory illusions or motor
      drift, we hypothesized that the change in COP displacement with locking would be
      reduced when participants were provided visual confirmation of COM stabilization
      (COM feedback), or when they were aware of the position of the COP throughout the
      trial (COP feedback). Confirming our previous results, increases in COP
      displacement were observed when movements of the COM were stabilized. In
      addition, our results showed that increases in COP displacement could not be
      explained by the presence of sensory illusions or motor drift, since increases in
      COP were observed despite being provided convincing evidence that the COM had
      been stabilized, and when participants were aware of their COP position
      throughout the trial. These results provide further support for an exploratory
      role of postural sway. The theoretical basis of current clinical practices
      designed to deal with balance control deficits due to age or disease is typically
      based on the opinion that increases in sway are a consequence of a failing
      balance control system. Our results suggest that this may not be the case, and if
      sway is in fact exploratory, a serious re-evaluation of current clinical
      practices may be warranted.

PMID- 21867744
TI  - Fatty acid amide hydrolase expression during retinal postnatal development in
      rats.
AB  - The endocannabinoid (eCB) system is thought to participate in developmental
      processes in the CNS. The rodent retina represents a valuable model to study CNS
      development because it contains well-identified cell types with established
      developmental timelines. The distribution of cannabinoid receptor type 1 (CB1R)
      was recently revealed in the developing retina; however, the expression patterns
      of other elements of this system remain unknown. In this study, we investigated
      the expression pattern of the degradative enzyme fatty acid amide hydrolase
      (FAAH), a key regulator of the eCB system, in the rat retina during postnatal
      development. To identify the cells expressing the enzyme, co-stainings were
      carried out for FAAH and retinal cell type markers. FAAH was expressed at
      postnatal day (P) 1 in ganglion and cholinergic amacrine cells. In the course of
      development, it appeared in cones, horizontal, and bipolar cells. For most cell
      types (horizontal, cholinergic amacrine cells, and cone bipolar cells), FAAH was
      transiently expressed, suggesting an important redistribution of the enzyme
      during postnatal development and thus a potential role of the eCB system in
      developmental processes. Our results also indicated that, in the adult retina,
      FAAH is expressed in cones, rod bipolar cells, and some retinal ganglion cells.
      The presence of FAAH in adult animals supports the hypothesis that the eCB system
      is involved in retinal functions. Overall these results indicate that, as shown
      in other structures of the brain, the eCB system could play an instrumental role
      in the development and function of the retina.

PMID- 21867747
TI  - The screening toolbox of bioactive substances from natural products: a review.
AB  - Hunting lead compounds from natural products plays a vital role in finding
      successful drug candidates. The efficiency of screening campaigns is mainly
      determined by the validity of selected screening models. To screen desired lead
      compounds, researchers have developed a plethora of experimental screening
      models. However, the considerable diversity of screening models from animal
      models, tissue models, to cell models and so on, may cause some trouble in
      choosing the suitable one. This review provides a toolbox of experimental
      screening models that have been used to discover new drug candidates from natural
      products. Two screening indexes are designed for different research directions in
      this screening toolbox. Index I is proposed from the direction of screening
      different objective substance populations, including plant extracts, active
      fractions and pure compounds; index Pi is according to screening different drug
      properties, including pharmacological properties, pharmacokinetic properties and
      affinity binding properties. We hope that the abbreviated bibliographies will
      help readers to quickly retrieve useful information by two screening indexes and
      provide certain reference value for choosing more appropriate screening models.
      Finally, we discuss ways of improving model systems, as well as future
      directions.

PMID- 21867746
TI  - Enhanced neurodegeneration after a high dose of methamphetamine in adenosine A3
      receptor null mutant mice.
AB  - Previous reports have indicated that adenosine A3 receptor (A3R) knockout mice
      are more sensitive to ischemic or hypoxic brain injury. The purpose of this study
      was to examine if suppression of A3R expression is associated with increase in
      sensitivity to injury induced by a high dose of methamphetamine (Meth). Adult
      male A3R null mutant (-/-) mice and their controls (+/+) were injected with four
      doses (2 h apart) of Meth (10 mg/kg) or saline. Animals were placed in a
      behavioral activity chamber, equipped with food and water, for 52 h starting from
      one day after injections. The first 4 h were used for studying exploratory
      behaviors, and the next 48 h were used to measure locomotor activity. High doses
      of Meth equally reduced the 4-h exploratory behavior in -/- and +/+ mice. Meth
      suppressed locomotor activity between 4 and 52 h in both groups, with a greater
      reduction being found in the -/- mice. Brain tissues were collected at 3 days
      after the Meth or saline injections. Meth treatment reduced striatal dopamine
      (DA) levels in both +/+ and -/- mice with an increase in 3,4
      dihydroxyphenylacetic acid (DOPAC)/DA ratio being found only in -/- animals. Meth
      also significantly increased ionized calcium-binding adaptor molecule 1 (Iba-1)
      and cleaved caspase-3 level in striatum, as well as Iba-1 and TNFalpha mRNA
      expression in nigra in -/-, compared to +/+, mice. Previous studies have shown
      that pharmacological suppression of vesicular monoamine transport 2 (VMAT2) by
      reserpine enhanced Meth toxicity by increasing cytosolic DA and inflammation. A
      significant reduction in striatal VMAT2 expression was found in -/- mice compared
      to +/+ mice, suggesting that increase in sensitivity to Meth injury in -/- mice
      may be related to a reduction in VMAT2 expression in these mice. In conclusion,
      our data suggest that A3R -/- mice are more sensitive to high doses of Meth.

PMID- 21867745
TI  - Investigating striatal function through cell-type-specific manipulations.
AB  - The striatum integrates convergent input from the cortex, thalamus, and midbrain,
      and has a powerful influence over motivated behavior via outputs to downstream
      basal ganglia nuclei. Although the anatomy and physiology of distinct classes of
      striatal neurons have been intensively studied, the specific functions of these
      cell subpopulations have been more difficult to address. Recently, application of
      new methodologies for perturbing activity and signaling in different cell types
      in vivo has begun to allow direct tests of the causal roles of striatal neurons
      in behavior.

PMID- 21867748
TI  - Molecular assay optimized by Taguchi experimental design method for venous
      thromboembolism investigation.
AB  - Two mutations - Factor V Leiden (1691G > A) and the 20210G > A on the Prothrombin
      gene - are key risk factors for a frequent and potentially fatal disorder called
      Venous Thromboembolism. These molecular alterations can be investigated using
      real-time Polymerase Chain Reaction (PCR) with Fluorescence Resonance Energy
      Transfer (FRET) probes and distinct DNA pools for both factors. The objective of
      this paper is to present an application of Taguchi Experimental Design Method to
      determine the best parameters adjustment of a Molecular Assays Process in order
      to obtain the best diagnostic result for Venous Thromboembolism investigation.
      The complete process contains six three-level factors which usually demands 729
      experiments to obtain the final result, if using a Full Factorial Array. In this
      research, a Taguchi L27 Orthogonal Array is chosen to optimize the analysis and
      reduce the number of experiments to 27 without degrading the final result
      accuracy. The application of this method can lessen the time and cost necessary
      to achieve the best operation condition for a required performance. The results
      is proven in practice and confirmed that the Taguchi method can really offer a
      good approach for clinical assay efficiency and effectiveness improvement even
      though the clinical diagnostics can be based on the use of qualitative
      techniques.

PMID- 21867749
TI  - Effects of heme oxygenase-1 on induction and development of chemically induced
      squamous cell carcinoma in mice.
AB  - Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may
      protect neoplastic cells against anticancer therapies, thereby promoting the
      progression of growing tumors. Our aim was to investigate the role of HO-1 in
      cancer induction. Experiments were performed in HO-1(+/+), HO-1(+/-), and HO-1(-/
      ) mice subjected to chemical induction of squamous cell carcinoma with 7,12
      dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate. Measurements of
      cytoprotective genes in the livers evidenced systemic oxidative stress in the
      mice of all the HO-1 genotypes. Carcinogen-induced lesions appeared earlier in HO
      1(-/-) and HO-1(+/-) than in wild-type animals. They also contained much higher
      concentrations of vascular endothelial growth factor and keratinocyte
      chemoattractant, but lower levels of tumor necrosis factor-alpha and interleukin
      12. Furthermore, tumors grew much larger in HO-1 knockouts than in the other
      groups, which was accompanied by an increased rate of animal mortality. However,
      pathomorphological analysis indicated that HO-1(-/-) lesions were mainly large
      but benign papillomas. In contrast, in mice expressing HO-1, most lesions
      displayed dysplastic features and developed to invasive carcinoma. Thus, HO-1 may
      protect healthy tissues against carcinogen-induced injury, but in already growing
      tumors it seems to favor their progression toward more malignant forms.

PMID- 21867751
TI  - (1)H NMR based metabolomics of CSF and blood serum: a metabolic profile for a
      transgenic rat model of Huntington disease.
AB  - Huntington disease (HD) is a hereditary brain disease. Although the causative
      gene has been found, the exact mechanisms of the pathogenesis are still unknown.
      Recent investigations point to metabolic and energetic dysfunctions in HD
      neurons. Both univariate and multivariate analyses were used to compare proton
      nuclear magnetic resonance spectra of serum and cerebrospinal fluid (CSF) taken
      from presymptomatic HD transgenic rats and their wild-type littermates. N
      acetylaspartate (NAA), was found to be significantly decreased in the serum of HD
      rats compared to wild-type littermates. Moreover, in the serum their levels of
      glutamine, succinic acid, glucose and lactate are significantly increased as
      well. An increased concentration of lactate and glucose is also found in CSF.
      There is a 1:1 stoichiometry coupling glucose utilization and glutamate cycling.
      The observed increase in the glutamine concentration, which indicates a shutdown
      in the neuronal-glial glutamate-glutamine cycling, results therefore in an
      increased glucose concentration. The elevated succinic acid concentration might
      be due to an inhibition of succinate dehydrogenase, an enzyme linked to the
      mitochondrial respiratory chain and TCA cycle. Moreover, reduced levels of NAA
      may reflect an impairment of mitochondrial energy production. In addition, the
      observed difference in lactate supports a deficiency of oxidative energy
      metabolism in rats transgenic for HD as well. The observed metabolic alterations
      seem to be more profound in serum than in CSF in presymptomatic rats. All
      findings suggest that even in presymptomatic rats, a defect in energy metabolism
      is already apparent. These results support the hypothesis of mitochondrial energy
      dysfunction in HD.

PMID- 21867750
TI  - Selective changes in white matter integrity in MCI and older adults with
      cognitive complaints.
AB  - BACKGROUND: White matter changes measured using diffusion tensor imaging have
      been reported in Alzheimer's disease and amnestic mild cognitive impairment, but
      changes in earlier pre-mild cognitive impairment stages have not been fully
      investigated. METHODS: In a cross-sectional analysis, older adults with mild
      cognitive impairment (n=28), older adults with cognitive complaints but without
      psychometric impairment (n=29) and healthy controls (n=35) were compared.
      Measures included whole-brain diffusion tensor imaging, T1-weighted structural
      magnetic resonance imaging, and neuropsychological assessment. Diffusion images
      were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional
      anisotropy and mean, axial, and radial diffusivities were assessed and compared
      between groups. Significant tract clusters were extracted in order to perform
      further region of interest comparisons. Brain volume was estimated using
      FreeSurfer based on T1 structural images. RESULTS: The mild cognitive impairment
      group showed lower fractional anisotropy and higher radial diffusivity than
      controls in bilateral parahippocampal white matter. When comparing extracted
      diffusivity measurements from bilateral parahippocampal white matter clusters,
      the cognitive complaint group had values that were intermediate to the mild
      cognitive impairment and healthy control groups. Group difference in diffusion
      tensor imaging measures remained significant after controlling for hippocampal
      atrophy. Across the entire sample, diffusion tensor imaging indices in
      parahippocampal white matter were correlated with memory function. CONCLUSIONS:
      These findings are consistent with previous results showing changes in
      parahippocampal white matter in Alzheimer's disease and mild cognitive impairment
      compared to controls. The intermediate pattern found in the cognitive complaint
      group suggests the potential of diffusion tensor imaging to contribute to earlier
      detection of neurodegenerative changes during prodromal stages. This article is
      part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative
      disease.

PMID- 21867752
TI  - A time to experience and a time to narrate.
AB  - Based on our experience of time as a dimension of our life, it appears a strong
      opposition between the time of the session and that of the narration of the cure.
      Indeed, the session may be conceived as relevant of an experimental methodology,
      reproducible during the time of the session, so that activation of some brain
      areas may be revealed by brain imaging methods. Given the recent findings on
      empathy, brain imaging should be applied to the patient but also to the
      therapist. Inversely, brain imaging might be not adapted to deal with the course
      of the cure, along the sessions, to disclose possible neuro-physiological
      reorganizations matching psychic improvement. The patient builds his/her personal
      history in order to be heard by the therapist. Transference and
      countertransference have here a heavy impact. It seems more adequate to use
      historical methods to deal with these data: time does not duplicate. However,
      Kandel proposes to make psychoanalysis more scientific by using brain imaging to
      show that some functional reorganization of brain areas could be the result of
      psychoanalysis. Unfortunately, the map cannot be confused with the territory. The
      question of the scientific dimension of Human Sciences and of History remains
      widely opened. Great authors, such as Balzac and Proust thought that their work
      contributed to scientific psychology. Their legacy in this field appears
      important to take into account.

PMID- 21867753
TI  - Decreased CREB levels suppress epilepsy.
AB  - Epilepsy is a common neurologic disorder yet no treatments aimed at preventing
      epilepsy have been developed. Several molecules including genes containing cAMP
      response elements (CREs) in their promoters have been identified that contribute
      to the development of epilepsy, a process called epileptogenesis. When
      phosphorylated cAMP response element binding protein (CREB) increases
      transcription from CRE regulated promoters. CREB phosphorylation is increased in
      rodent epilepsy models, and in the seizure onset region of humans with medically
      intractable epilepsy (Rakhade et al., 2005; Lee et al., 2007; Lund et al., 2008).
      Here we show that mice with decreased CREB levels (CREB(alpha?) mutants) have a
      ~50% reduction in spontaneous seizures following pilocarpine induced status
      epilepticus (SE) and require more stimulation to electrically kindle. Following
      SE, brain derived neurotrophic factor (BDNF) and inducible cAMP early repressor
      (ICER) mRNAs are differentially up-regulated in the hippocampus and cortex of the
      CREB(alpha?) mutants compared to wild-type mice, which may be contributing to
      differences in the severity of epilepsy. In contrast, we found no difference in
      KCC2 mRNA levels between the CREB(alpha?) and wild-type mice after SE. The
      mechanism by which BDNF and ICER mRNAs increase specifically in the CREB(alpha?)
      compared to wild-type mice following SE is not known. We did, however, find an
      increase in specific cAMP response element modulator (CREM) mRNA transcripts in
      the CREB(alpha?) mutants that might be responsible for the differential
      regulation of BDNF and ICER after SE. Altering CREB activity following a
      neurologic insult provides a therapeutic strategy for modifying epileptogenesis.

PMID- 21867754
TI  - Activated retinal glia mediated axon regeneration in experimental glaucoma.
AB  - Glaucoma, a leading cause of blindness, is a neurodegenerative disease
      characterized by progressive loss of retinal ganglion cell axons in the optic
      nerve and their cell bodies in the retina. Reactive retinal glial changes have
      been observed in glaucoma but the role of such glial changes in the pathogenesis
      of the condition remains unclear. In the present study we found that retinal
      ganglion cells in an experimental animal model of glaucoma have an increased axon
      regenerative potential. Regeneration of adult rat retinal ganglion cell axons
      after optic nerve crush was significantly increased in vivo when combined with
      intraocular pressure-induced experimental glaucoma. This enhanced axon
      regeneration response was correlated with a significant increase in activation of
      glial fibrillary acidic protein+retinal glia. Using a dissociated retinal
      ganglion cell culture model we showed that reducing the number of activated
      retinal glia with a glial specific toxin, alpha-Aminoadipic acid, significantly
      reduced the growth potential of retinal ganglion cells from glaucomatous rat
      eyes, suggesting that activated retinal glia mediate, at least in part, the
      growth promoting effect. This was shown to be mediated by both membrane-bound and
      soluble glial-derived factors. Neurotrophin and ciliary neurotrophic/leukemia
      inhibitory factor blockers did not affect the regenerative potential, excluding
      these growth factors as principal mediators of the enhanced growth response
      occurring in glaucomatous retinal cultures. These observations are the first to
      reveal that retinal ganglion cells from glaucomatous rat eyes have an enhanced
      regenerative capacity. Furthermore, our results suggest that activated retinal
      glia mediate at least part of this response. Further work to understand and
      enhance the regeneration-promoting effect of activated retinal glia is required
      to determine if this approach could be useful as part of a therapeutic strategy
      to encourage optic nerve regeneration in glaucoma.

PMID- 21867755
TI  - Sensitive quantification of isoprenoid cytokinins in plants by selective
      immunoaffinity purification and high performance liquid chromatography-quadrupole
      time of flight mass spectrometry.
AB  - In this work, we developed a novel class-specific immunoaffinity column for the
      natural isoprenoid cytokinins (CTKs) by using trans-zeatin riboside as the hapten
      to generate a complete antigen. By combination with a mixed-mode solid phase
      extraction step for pre-cleanup and a high performance liquid chromatography
      quadrupole-time of flight mass spectrometry for the quantification, an efficient
      analytical protocol was established which allowed simultaneous quantification of
      eight endogenous isoprenoid CTKs in Arabidopsis thaliana leaves with a wide
      linear range from 25 to 500pg/g fresh weight and a detection limit of 12.5pg/g
      fresh weight. The method will be very useful for comprehensive research on the
      networks of signaling interactions of the active phytohormones and their
      regulation of the plant functions.

PMID- 21867756
TI  - Identification of influenza virus inhibitors which disrupt of viral polymerase
      protein-protein interactions.
AB  - Due to their ability to rapidly mutate, influenza viruses quickly develop
      resistance against many antiviral substances, leading to an urgent need for new
      compounds. The trimeric viral polymerase complex, a major target for the
      development of new inhibitors, must be assembled from the PB1, PB2, and PA
      subunits for successful infection. Here, we describe ELISA-based assays which
      allow the identification of peptides which impair polymerase complex formation.
      Since the protein-protein interaction domains of the viral polymerase are highly
      conserved, these inhibitors are also predicted to be active against a broad range
      of influenza strains. Using this method, identification of small molecules and
      lead compounds against influenza A and B viruses should be feasible.

PMID- 21867757
TI  - Maximal transcriptional activation of piscine soluble Toll-like receptor 5 by the
      NF-kappaB subunit p65 and flagellin.
AB  - Toll-like receptor 5 (TLR5), which is highly conserved from lower to higher
      vertebrates, is an important pattern recognition receptor (PRR) for bacterial
      flagellin. However, a soluble form of TLR5 (TLR5S) was identified in fish that is
      not present in mammals. To better understand the transcriptional regulation of
      TLR5S gene in fish, we determined the TLR5S 5'-flanking sequence region from
      flounder (Paralichthys olivaceus) and assayed its promoter activity in Hirame
      natural embryo (HINAE) cells. The 5'-flanking region of TLR5S (715 bp) contains
      sequence elements for two AP-1 binding sites, two C/EBP sites, and one NF-kappaB
      site. To elucidate the functional significance of these sites, deletion clones
      and a site-directed mutant of NF-kappaB were generated. We estimated the
      luciferase activity in flagellin- or lipopolysaccharide-stimulated HINAE cells.
      The co-transfection of p65 with the wild-type TLR5S promoter greatly increased
      luciferase activity by more than nine-fold compared with the NF-kappaB mutant.
      Wild-type TLR5S promoter activity was increased synergistically by more than
      159.5-fold in the presence of flagellin and p65. Furthermore, it was determined
      that the level of TRL5S mRNA was up-regulated by p65 and flagellin using a
      quantitative PCR. Additionally, translocation of TLR5S in the HINAE-TLR5S stable
      cell line after flagellin stimulation was observed by confocal microscopy. These
      results suggest that NF-kappaB and flagellin are essential components that act as
      a transcription factor and ligand, respectively, for maximal induction of the
      TLR5S promoter.

PMID- 21867758
TI  - Changing the structure of complex visuo-motor sequences selectively activates the
      fronto-parietal network.
AB  - Previous brain imaging studies investigating motor sequence complexity have
      mainly examined the effect of increasing the length of pre-learned sequences. The
      novel contribution of this research is that we varied the structure of complex
      visuo-motor sequences along two different dimensions using mxn paradigm. The
      complexity of sequences is increased from 12 movements (organized as a 2*6 task)
      to 24 movements (organized as 4*6 and 2*12 tasks). Behavioral results indicate
      that although the success rate attained was similar across the two complex tasks
      (2*12 and 4*6), a greater decrease in response times was observed for the 2*12
      compared to the 4*6 condition at an intermediate learning stage. This decrease is
      possibly related to successful chunking across sets in the 2*12 task. In line
      with this, we observed a selective activation of the fronto-parietal network.
      Shifts of activation were observed from the ventral to dorsal prefrontal, lateral
      to medial premotor and inferior to superior parietal cortex from the early to
      intermediate learning stage concomitant with an increase in hyperset length. We
      suggest that these selective activations and shifts in activity during complex
      sequence learning are possibly related to chunking of motor sequences.

PMID- 21867759
TI  - 3D fiber tractography with susceptibility tensor imaging.
AB  - Gradient-echo MRI has revealed anisotropic magnetic susceptibility in the brain
      white matter. This magnetic susceptibility anisotropy can be measured and
      characterized with susceptibility tensor imaging (STI). In this study, a method
      of fiber tractography based on STI is proposed and demonstrated in the mouse
      brain. STI experiments of perfusion-fixed mouse brains were conducted at 7.0T.
      The magnetic susceptibility tensor was calculated for each voxel with
      regularization and decomposed into its eigensystem. The major eigenvector is
      found to be aligned with the underlying fiber orientation. Following the
      orientation of the major eigenvector, we are able to map distinctive fiber
      pathways in 3D. As a comparison, diffusion tensor imaging (DTI) and DTI fiber
      tractography were also conducted on the same specimens. The relationship between
      STI and DTI fiber tracts was explored with similarities and differences
      identified. It is anticipated that the proposed method of STI tractography may
      provide a new way to study white matter fiber architecture. As STI tractography
      is based on physical principles that are fundamentally different from DTI, it may
      also be valuable for the ongoing validation of DTI tractography.

PMID- 21867760
TI  - The danger of systematic bias in group-level FMRI-lag-based causality estimation.
AB  - Schippers, Renken and Keysers (NeuroImage, 2011) present a simulation of multi
      subject lag-based causality estimation. We fully agree that single-subject
      evaluations (e.g., Smith et al., 2011) need to be revisited in the context of
      multi-subject studies, and Schippers' paper is a good example, including detailed
      multi-level simulation and cross-subject statistical modelling. The authors
      conclude that "the average chance to find a significant Granger causality effect
      when no actual influence is present in the data stays well below the p-level
      imposed on the second level statistics" and that "when the analyses reveal a
      significant directed influence, this direction was accurate in the vast majority
      of the cases". Unfortunately, we believe that the general meaning that may be
      taken from these statements is not supported by the paper's results, as there may
      in reality be a systematic (group-average) difference in haemodynamic delay
      between two brain areas. While many statements in the paper (e.g., the final two
      sentences) do refer to this problem, we fear that the overriding message that
      many readers may take from the paper could cause misunderstanding.

PMID- 21867761
TI  - High field magnetic resonance microscopy of the human hippocampus in Alzheimer's
      disease: quantitative imaging and correlation with iron.
AB  - We report R(2) and R(2) in human hippocampus from five unfixed post-mortem
      Alzheimer's disease (AD) and three age-matched control cases. Formalin-fixed
      tissues from opposing hemispheres in a matched AD and control were included for
      comparison. Imaging was performed in a 600MHz (14T) vertical bore magnet at MR
      microscopy resolution to obtain R(2) and R(2) (62 MUm*62 MUm in-plane, 80 MUm
      slice thickness), and R(1) at 250 MUm isotropic resolution. R(1), R(2) and R(2)
      maps were computed for individual slices in each case, and used to compare
      subfields between AD and controls. The magnitudes of R(2) and R(2) changed very
      little between AD and control, but their variances in the Cornu Ammonis and
      dentate gyrus were significantly higher in AD compared for controls (p<0.001). To
      investigate the relationship between tissue iron and MRI parameters, each tissue
      block was cryosectioned at 30 MUm in the imaging plane, and iron distribution was
      mapped using synchrotron microfocus X-ray fluorescence spectroscopy. A positive
      correlation of R(2) and R(2)* with iron was demonstrated. While studies with
      fixed tissues are more straightforward to conduct, fixation can alter iron status
      in tissues, making measurement of unfixed tissue relevant. To our knowledge,
      these data represent an advance in quantitative imaging of hippocampal subfields
      in unfixed tissue, and the methods facilitate direct analysis of the relationship
      between MRI parameters and iron. The significantly increased variance in AD
      compared for controls warrants investigation at lower fields and in-vivo, to
      determine if this parameter is clinically relevant.

PMID- 21867762
TI  - Identification and characterisation of midbrain nuclei using optimised functional
      magnetic resonance imaging.
AB  - Localising activity in the human midbrain with conventional functional MRI (fMRI)
      is challenging because the midbrain nuclei are small and located in an area that
      is prone to physiological artefacts. Here we present a replicable and automated
      method to improve the detection and localisation of midbrain fMRI signals. We
      designed a visual fMRI task that was predicted would activate the superior
      colliculi (SC) bilaterally. A limited number of coronal slices were scanned,
      orientated along the long axis of the brainstem, whilst simultaneously recording
      cardiac and respiratory traces. A novel anatomical registration pathway was used
      to optimise the localisation of the small midbrain nuclei in stereotactic space.
      Two additional structural scans were used to improve registration between
      functional and structural T1-weighted images: an echo-planar image (EPI) that
      matched the functional data but had whole-brain coverage, and a whole-brain T2
      weighted image. This pathway was compared to conventional registration pathways,
      and was shown to significantly improve midbrain registration. To reduce the
      physiological artefacts in the functional data, we estimated and removed
      structured noise using a modified version of a previously described physiological
      noise model (PNM). Whereas a conventional analysis revealed only unilateral SC
      activity, the PNM analysis revealed the predicted bilateral activity. We
      demonstrate that these methods improve the measurement of a biologically
      plausible fMRI signal. Moreover they could be used to investigate the function of
      other midbrain nuclei.

PMID- 21867763
TI  - Cross-subject workload classification with a hierarchical Bayes model.
AB  - Most of the current EEG-based workload classifiers are subject-specific; that is,
      a new classifier is built and trained for each human subject. In this paper we
      introduce a cross-subject workload classifier based on a hierarchical Bayes
      model. The cross-subject classifier is trained and tested with data from a group
      of subjects. In our work, it was trained and tested on EEG data collected from 8
      subjects as they performed the Multi-Attribute Task Battery across three levels
      of difficulty. The accuracy of this cross-subject classifier is stable across the
      three levels of workload and comparable to a benchmark subject-specific neural
      network classifier.

PMID- 21867764
TI  - Cerebral responses to infant-directed speech and the effect of talker
      familiarity.
AB  - A number of behavioral studies suggest that infant-directed speech (IDS) plays a
      more important role in facilitating both: a) speech perception, and b) adult
      infant social interactions than does adult-directed speech (ADS), and hence that
      IDS contributes to subsequent social and language development. However neural
      substrates that may underlie these IDS functions have not been examined. The
      present study examined cerebral hemodynamic responses to IDS in 48 infants (4-13
      months of age) using near-infrared spectroscopy (NIRS). Japanese sentences
      uttered by the infants' own mothers and by unfamiliar mothers were used to record
      activations in temporal and frontal area separately. Increased activations were
      observed predominantly in infants' left and right temporal areas when they
      listened to IDS rather than to ADS when both involved voices of their own and
      unfamiliar mothers. In contrast, significantly greater activations were observed
      in the frontal area when infants listened to IDS produced by their own mothers,
      not when IDS arose from unfamiliar mothers. Furthermore, the present results
      indicate that responses to IDS do vary as a function of the infant's age and the
      talker familiarity. These findings suggest a differential function for frontal
      and temporal areas in processing infant-directed speech by the different
      speakers.

PMID- 21867765
TI  - Mitochondrial and nuclear DNA phylogenies reveal a complex evolutionary history
      in the Australasian robins (Passeriformes: Petroicidae).
AB  - The Australasian robins (Petroicidae) comprise a relatively homogeneous group of
      small to medium-sized insectivorous birds. Their center of diversity is Australia
      and New Guinea (40 species) but seven species have managed to colonize
      geographically distant islands such as Tanimbar, New Britain, New Zealand, New
      Caledonia, Norfolk Island, Vanuatu, Solomon Islands, Fiji and Samoa. To resolve
      the evolutionary relationships within the Petroicidae, we here present the
      results of a phylogenetic analysis of sequence data from two mitochondrial genes
      (ND2, CO1) and one nuclear intron (beta-Fibrinogen intron 5) for all 14 genera
      and 40 of the 46 currently recognized species. All phylogenetic analyses
      identified six primary lineages, treated here as subfamilies, within the
      Petroicidae: (1) Eopsaltriinae comprising Eopsaltria (excluding E. flaviventris),
      Tregellasia, Peneothello, Melanodryas, Poecilodryas and Heteromyias; (2)
      Drymodinae comprising Drymodes; (3) Microecinae comprising Microeca, Monachella
      and Eopsaltria flaviventris; (4) Petroicinae comprising Petroica and Eugerygone;
      (5) Pachycephalopsinae comprising Pachycephalopsis; and (6) Amalocichlinae
      comprising Amalocichla. The genera Eopsaltria, Microeca, Peneothello and
      Poecilodryas were found to be paraphyletic. Based on assessments of phylogenetic
      branching patterns and/or DNA divergence it also was apparent that
      Eopsaltriaaustralis, Tregellasialeucops, Melanodryascucullata,
      Heteromyiasalbispecularis, Drymodessupercilious and Microecaflavigaster may each
      comprise more than one species. The Petroicidae display a complex biogeographical
      history involving repeated radiations both within, and across Australia and New
      Guinea. It appears that dispersal into smaller islands such as New Britain,
      Tanimbar and the South Pacific has only been undertaken by species with a
      "flycatcher" body form.

PMID- 21867766
TI  - Phylogenetic relationships of the mockingbirds and thrashers (Aves: Mimidae).
AB  - The mockingbirds, thrashers and allied birds in the family Mimidae are broadly
      distributed across the Americas. Many aspects of their phylogenetic history are
      well established, but there has been no previous phylogenetic study that included
      all species in this radiation. Our reconstructions based on mitochondrial and
      nuclear DNA sequence markers show that an early bifurcation separated the Mimidae
      into two clades, the first of which includes North and Middle American taxa
      (Melanotis, Melanoptila, Dumetella) plus a small radiation that likely occurred
      largely within the West Indies (Ramphocinclus, Allenia, Margarops,
      Cinclocerthia). The second and larger radiation includes the Toxostoma thrasher
      clade, along with the monotypic Sage Thrasher (Oreoscoptes) and the
      phenotypically diverse and broadly distributed Mimus mockingbirds. This
      mockingbird group is biogeographically notable for including several lineages
      that colonized and diverged on isolated islands, including the Socorro
      Mockingbird (Mimus graysoni, formerly Mimodes) and the diverse and historically
      important Galapagos mockingbirds (formerly Nesomimus). Our reconstructions
      support a sister relationship between the Galapagos mockingbird lineage and the
      Bahama Mockingbird (M. gundlachi) of the West Indies, rather than the Long-tailed
      Mockingbird (M. longicaudatus) or other species presently found on the South
      American mainland. Relationships within the genus Toxostoma conflict with
      traditional arrangements but support a tree based on a preivous mtDNA study. For
      instance, the southern Mexican endemic Ocellated Thrasher (T. ocellatum) is not
      an isolated sister species of the Curve-billed thrasher (T. curvirostre).

PMID- 21867768
TI  - Expression and regulation by thyroid hormone (TH) of zebrafish IGF-I gene and
      amphioxus IGFl gene with implication of the origin of TH/IGF signaling pathway.
AB  - Thyroid hormone (TH)/insulin-like growth factor (IGF) signaling pathway has been
      identified in all the vertebrates, but its evolutionary origin remains elusive.
      In this study we examined the expression profiles in vitro as well as in vivo of
      the IGF-I gene of fish Danio rerio (vertebrate) and the IGF-like gene (IGFl) of
      amphioxus Branchiostoma japonicum (protochordate) following T(3) treatment. Our
      results showed that T(3) was able to enhance hepatic IGF-I/IGFl gene expression
      in vitro in both zebrafish and amphioxus in a dose-dependent manner. This T(3)
      induced hepatic expression of IGF-I/IGFl genes in both species was significantly
      inhibited by the T(3)-specific inhibitor DEA, indicating the specificity of IGF
      I/IGFl gene regulation by T(3). At 100nM T(3), in both the long (42h) and short
      (8h) time course experiments, the IGF-I/IGFl gene expression profiles following
      T(3) treatment in the tissue cultures of both species exhibited closely similar
      pattern and trend. Moreover, exposure of zebrafish and amphioxus to T(3)in vivo
      for 72h induced a significant increase in the expression of IGF-I/IGFl genes in
      both the liver and the hepatic caecum. These data together suggest that amphioxus
      and zebrafish both share a similar regulatory mechanism of IGF gene expression in
      response to T(3), providing an evidence for the presence of a vertebrate-like
      TH/IGF signaling pathway in the protochordate amphioxus.

PMID- 21867769
TI  - Control of host inflammatory responsiveness by indigenous microbiota reveals an
      adaptive component of the innate immune system.
AB  - We are not alone. The indigenous microbiota colonizes exposed surfaces and aids
      their hosts in several physiological activities. The transition between a non
      colonized to a colonized state is associated with modification on the pattern of
      host inflammatory responsiveness. Therefore, innate immunity adapts to the
      colonized state of the host, suggesting that there is an acquired component in
      innate immune responses.

PMID- 21867767
TI  - RNA splicing in regulation of nitric oxide receptor soluble guanylyl cyclase.
AB  - Soluble guanylyl cyclase (sGC) is a key protein in the nitric oxide (NO)/-cGMP
      signaling pathway. sGC activity is involved in a number of important
      physiological processes including smooth muscle relaxation, neurotransmission and
      platelet aggregation and adhesion. Regulation of sGC expression and activity
      emerges as a crucial factor in control of sGC function in normal and pathological
      conditions. Recently accumulated evidence strongly indicates that the regulation
      of sGC expression is a complex process modulated on several levels including
      transcription, post-transcriptional regulation, translation and protein
      stability. Presently our understanding of mechanisms governing regulation of sGC
      expression remains very limited and awaits systematic investigation. Among other
      ways, the expression of sGC subunits is modulated at the levels of mRNA abundance
      and transcript diversity. In this review we summarize available information on
      different mechanisms (including transcriptional activation, mRNA stability and
      alternative splicing) involved in the modulation of mRNA levels of sGC subunits
      in response to various environmental clues. We also summarize and cross-reference
      the information on human sGC splice forms available in the literature and in
      genomic databases. This review highlights the fact that the study of the
      biological role and regulation of sGC splicing will bring new insights to our
      understanding of NO/cGMP biology.

PMID- 21867770
TI  - Characterization of Fasciola spp. in Myanmar on the basis of spermatogenesis
      status and nuclear and mitochondrial DNA markers.
AB  - Fasciola spp. in Myanmar were characterized on the basis of spermatogenesis
      status and DNA markers of nuclear internal transcribed spacer 1 (ITS1) and
      mitochondrial NADH dehydrogenase subunit 1 (nad1). We collected 88 adult flukes
      from Yangon, Lashio, and Myitkyina. Spermatogenesis status was analyzed by the
      presence of sperm in the seminal vesicles, and 8 aspermic and 80 spermic flukes
      were detected. The flukes were identified on the basis of spermatogenesis status
      and ITS1 types which were analyzed by a PCR-RFLP method, and 80 spermic flukes
      were identified as F. gigantica. A very low detection rate of aspermic Fasciola
      sp. indicated that they are not established in Myanmar. In phylogenetic analyses,
      the 7 aspermic Fasciola sp. from Myitkyina displayed a haplotype in nad1
      sequence, which was identical to that of aspermic Fasciola sp. from other Asian
      countries including China. Therefore, they were probably introduced from China
      through an infected domestic ruminant. On the other hand, 17 nad1 haplotypes
      detected in F. gigantica belonged to 2 clades unique to Myanmar, each with a
      distinct founder haplotype in a network analysis. This indicated a unique history
      of F. gigantica introduction into Myanmar involving ancient artificial movements
      of domestic ruminants.

PMID- 21867771
TI  - Discovery of human opisthorchiasis: a mysterious history.

PMID- 21867772
TI  - Molecular cloning and characterisation of a novel P-glycoprotein in the salmon
      louse Lepeophtheirus salmonis.
AB  - The salmon louse, Lepeophtheirus salmonis, is a crustacean ectoparasite of
      salmonid fish. At present, sea louse control on salmon farms relies heavily upon
      chemical treatments. Drug efflux transport, mediated by ABC transporters such as
      P-glycoprotein (Pgp), represents a major mechanism for drug resistance in
      parasites. We report here the molecular cloning of a new Pgp from the salmon
      louse, called SL-PGY1. A partial Pgp sequence was obtained by searching sea louse
      ESTs, and extended by rapid amplification of cDNA ends (RACE). The open reading
      frame of SL-PGY1 encodes a protein of 1438 amino acids that possesses typical
      structural traits of P-glycoproteins, and shows a high degree of sequence
      homology to invertebrate and vertebrate P-glycoproteins. In the absence of drug
      exposure, SL-PGY1 mRNA expression levels did not differ between a drug
      susceptible strain of L. salmonis and a strain showing a ~7-fold decrease in
      sensitivity against emamectin benzoate, the active component of the in-feed sea
      louse treatment SLICE (Merck Animal Health). Aqueous exposure of the
      hyposensitive salmon louse strain to emamectin benzoate (24h, 410 MUg/L) provoked
      a 2.9-fold upregulation of SL-PGY1. Adult male lice of both strains showed a
      greater abundance of SL-PGY1 mRNA than adult females.

PMID- 21867773
TI  - Acute temperature and cadmium stress response characterization of small heat
      shock protein 27 in large yellow croaker, Larimichthys crocea.
AB  - Small heat shock proteins (sHSPs) are a group of molecular chaperones and play a
      crucial role in cell response to various stresses. In this study, we cloned and
      sequenced a small heat shock protein 27 (LcHSP27) cDNA from large yellow croaker,
      Larimichthys crocea. The full-length cDNA of LcHSP27 was 1227 bp, including a 5'
      terminal untranslated region (UTR) of 54 bp, a 3'-terminal UTR of 561 bp and an
      open reading frame (ORF) of 612 bp encoding a polypeptide of 203 amino acids.
      Three conserved phosphorylation sites of serine were identified in the deduced
      LcHSP27 amino acid sequence at positions 15, 91 and 95 respectively, and a
      typical alpha-crystallin domain was at positions 96-193. Phylogenetic analysis
      revealed that LcHSP27 was categorized together with the HSP27 obtained from other
      fish. And a closer phylogenetic relationship of HSP27 was found with HSP22, then
      HSP30. Quantitative real-time reverse transcription PCR (qRT-PCR) analysis
      indicated the strongest expression of LcHSP27 in heart. However, expression of
      LcHSP27 in other examined tissues including muscle, brain, liver, spleen, kidney,
      gill, and blood was very weak. The impact of temperature and cadmium (Cd(2+))
      stress on LcHSP27 expression was tested in liver and brain. The results showed
      that the levels of LcHSP27 expression increased significantly after low
      temperature (19 degrees C) and high temperature (27 degrees C and 31 degrees C)
      stress both in liver and brain. And low temperature stress induced a higher
      LcHSP27 expression in liver. More important, LcHSP27 expression showed a dramatic
      up-regulation after a combined stress of temperature and cadmium (p<0.05). These
      results reveal that HSP27 may play an important role in the large yellow croaker
      response to temperature and cadmium stress.

PMID- 21867774
TI  - TURF: toward a unified framework of EHR usability.
AB  - This paper presents a unified framework of EHR usability, called TURF, which is
      (1) a theory for describing, explaining, and predicting usability differences;
      (2) a method for defining, evaluating, and measuring usability objectively; (3) a
      process for designing built-in good usability; and (4) once fully developed, a
      potential principle for developing EHR usability guidelines and standards. TURF
      defines usability as how useful, usable, and satisfying a system is for the
      intended users to accomplish goals in the work domain by performing certain
      sequences of tasks. TURF provides a set of measures for each of the useful,
      usable, and satisfying dimensions of usability. TURF stands for task, user,
      representation, and function, which are the four components that determine the
      usability of an EHR system. These four components are described with theoretical
      descriptions along with examples of how usability is measured in several case
      studies. How TURF can be used to improve usability through redesign is also
      demonstrated in a case study. In summary, this paper states that usability can
      not only be defined scientifically under a coherent, unified framework, it can
      also be measured objectively and systematically.

PMID- 21867775
TI  - Multi-View Interaction Modelling of human collaboration processes: a business
      process study of head and neck cancer care in a Dutch academic hospital.
AB  - In the healthcare domain, human collaboration processes (HCPs), which consist of
      interactions between healthcare workers from different (para)medical disciplines
      and departments, are of growing importance as healthcare delivery becomes
      increasingly integrated. Existing workflow-based process modelling tools for
      healthcare process management, which are the most commonly applied, are not
      suited for healthcare HCPs mainly due to their focus on the definition of task
      sequences instead of the graphical description of human interactions. This paper
      uses a case study of a healthcare HCP at a Dutch academic hospital to evaluate a
      novel interaction-centric process modelling method. The HCP under study is the
      care pathway performed by the head and neck oncology team. The evaluation results
      show that the method brings innovative, effective, and useful features. First, it
      collects and formalizes the tacit domain knowledge of the interviewed healthcare
      workers in individual interaction diagrams. Second, the method automatically
      integrates these local diagrams into a single global interaction diagram that
      reflects the consolidated domain knowledge. Third, the case study illustrates how
      the method utilizes a graphical modelling language for effective tree-based
      description of interactions, their composition and routing relations, and their
      roles. A process analysis of the global interaction diagram is shown to identify
      HCP improvement opportunities. The proposed interaction-centric method has wider
      applicability since interactions are the core of most multidisciplinary patient
      care processes. A discussion argues that, although (multidisciplinary)
      collaboration is in many cases not optimal in the healthcare domain, it is
      increasingly considered a necessity to improve integration, continuity, and
      quality of care. The proposed method is helpful to describe, analyze, and improve
      the functioning of healthcare collaboration.

PMID- 21867777
TI  - Muscle type-specific expression of Zasp52 isoforms in Drosophila.
AB  - Zasp52 is a member of the PDZ-LIM domain protein family in Drosophila, which
      comprises Enigma, ENH, ZASP, Alp, CLP36, RIL, and Mystique in vertebrates.
      Drosophila Zasp52 colocalizes with integrins at myotendinous junctions and with
      alpha-actinin at Z-disks, and is required for muscle attachment as well as Z-disk
      assembly and maintenance. Here we document 13 Zasp52 splice variants giving rise
      to six different LIM domains. We demonstrate stage- and tissue-specific
      expression in different muscle types for Zasp52 isoforms encoding different LIM
      domains. In particular, LIM1b is expressed only in heart muscle and certain
      somatic muscles, implying muscle-specific functions in Z-disk assembly or
      maintenance.

PMID- 21867776
TI  - Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas.
AB  - Tbx2 and Tbx3 are closely related members of the T-box family of transcription
      factors that are important regulators during normal development as well as major
      contributors to human developmental syndromes when mutated. Although there is
      evidence for the involvement of Tbx2 and Tbx3 in pancreatic cancer, so far there
      are no reports characterizing the normal expression pattern of these genes in the
      pancreas. In this study, we examined spatial and temporal expression of Tbx2 and
      Tbx3 in mouse pancreas during development and in the adult using in situ
      hybridization and immunohistochemistry. Our results show that Tbx2 and Tbx3 are
      both expressed in the pancreatic mesenchyme throughout development beginning at
      embryonic day (E) 9.5. In addition, Tbx2 is expressed in pancreatic vasculature
      during development and in epithelial-derived endocrine and ductal cells during
      late fetal stages, postnatal development and in adult pancreas. In contrast, Tbx3
      is expressed in exocrine tissue in the postnatal and adult pancreas. Further our
      results demonstrate that Tbx2 and Tbx3 are expressed in tumor-derived endocrine
      and exocrine cell lines, respectively. These dynamic changes in the expression
      pattern of these transcription factors lay the foundation for investigation of
      potential roles in pancreas development.

PMID- 21867778
TI  - Old and new selective pressures on Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) has been affecting humans for millennia. There is increasing
      indication that human-adapted Mycobacterium tuberculosis complex (MTBC) has been
      co-evolving with different human populations. Some of the most important drivers
      of MTBC evolution have been the host immune response and human demography. These
      old selective forces have shaped many of the features of human TB we see today.
      Two new selective pressures have emerged only a few decades ago, namely HIV co
      infection and the use of anti-TB drugs. Here we discuss how the emergence of
      HIV/TB and drug resistance could impact the long-term balance between MTBC and
      its human host, and how these changes might influence the future evolutionary
      trajectory of MTBC.

PMID- 21867779
TI  - Berberine down-regulates the Th1/Th2 cytokine gene expression ratio in mouse
      primary splenocytes in the absence or presence of lipopolysaccharide in a
      preventive manner.
AB  - Berberine is a natural isoquinoline alkaloid. This study investigated the effects
      of berberine on cytokine gene expression in mouse primary splenocytes in the
      absence or presence of lipopolysaccharide (LPS) using 4 different experimental
      models in vitro. The relative expression of the following cytokine genes was
      determined using a real-time quantitative polymerase chain reaction assay: pro
      inflammatory tumor necrosis factor (TNF)-alpha, anti-inflammatory interleukin
      (IL)-10, T-helper type 1 (Th1) (IL-2), and Th2 (IL-4) cytokines. The results
      showed that berberine down-regulated ratios of the relative Th1 (IL-2)/Th2 (IL-4)
      cytokines expression fold in mouse primary splenocytes in the absence or presence
      of LPS in a preventive manner. This study suggests that berberine may possess
      anti-inflammatory potential by shifting the Th1/Th2 balance toward Th2
      polarization.

PMID- 21867780
TI  - Recombinant production and characterisation of two related GH5 endo-beta-1,4
      mannanases from Aspergillus nidulans FGSC A4 showing distinctly different
      transglycosylation capacity.
AB  - The glycoside hydrolase family 5 (GH5) endo-beta-1,4-mannanases ManA and ManC
      from Aspergillus nidulans FGSC A4 were produced in Pichia pastoris X33 and
      purified in high yields of 120 and 145mg/L, respectively, from the culture
      supernatants. Both enzymes showed increasing catalytic efficiency (k(cat)/K(M))
      towards beta-1,4 manno-oligosaccharides with the degree of polymerisation (DP)
      from 4 to 6 and also hydrolysed konjac glucomannan, guar gum and locust bean gum
      galactomannans. ManC had up to two-fold higher catalytic efficiency for DP 5 and
      6 manno-oligosaccharides and also higher activity than ManA towards mannans.
      Remarkably, ManC compared to ManA transglycosylated mannotetraose with formation
      of longer beta-1,4 manno-oligosaccharides 8-fold more efficiently and was able to
      use mannotriose, melezitose and isomaltotriose out of 36 tested acceptors
      resulting in novel penta- and hexasaccharides, whereas ManA used only mannotriose
      as acceptor. ManA and ManC share 39% sequence identity and homology modelling
      suggesting that they have very similar substrate interactions at subsites +1 and
      +2 except that ManC Trp283 at subsite +1 corresponded to Ser289 in ManA. Site
      directed mutagenesis to ManA S289W lowered K(M) for manno-oligosaccharides by 30
      45% and increased transglycosylation yield by 50% compared to wild-type.
      Conversely, K(M) for ManC W283S was increased, the transglycosylation yield was
      reduced by 30-45% and furthermore activity towards mannans decreased below that
      of ManA. This first mutational analysis in subsite +1 of GH5 endo-beta-1,4
      mannanases indicated that Trp283 in ManC participates in discriminating between
      mannan substrates with different extent of branching and has a role in
      transglycosylation and substrate affinity.

PMID- 21867782
TI  - Horam nonam exclamavit: sitio. The trace proteome of your daily vinegar.
AB  - The trace proteome of white-wine vinegar has been identified via capture with
      home-made combinatorial peptide ligand libraries under conditions mimicking
      reverse-phase capture, i.e. at pH 2.2 in presence of 0.1% trifluoroacetic acid. A
      total of 27 unique gene products have been identified, of which 10 specific of
      the database Vitis vinifera, 13 found in the general database
      Uniprot_viridiplantae and 4 in Swiss Prot_all entries. The most abundant species
      detected, on the basis of spectral counts, appears to be the whole genome shotgun
      sequence of line PN40024, scaffold_22 (a protein of the glycosyl hydrolase
      family). Curiously, up to the present, no information had been available on
      vinegar proteome.

PMID- 21867781
TI  - Analysis of hydrolyzable polyethylene glycol hydrogels and deproteinized bone
      mineral as delivery systems for glycosylated and non-glycosylated bone
      morphogenetic protein-2.
AB  - Bone morphogenetic proteins (BMP), in particular BMP-2, are the growth factors
      primarily responsible for osteoinduction. A knowledge of interactions between
      bone substitute materials and growth factor variants is crucial to designing bone
      substitutes with an ideal release profile. Here we compare glycosylated and non
      glycosylated recombinant human bone morphogenetic protein-2 (rhBMP-2) either
      incorporated into a hydrolyzable polyethylene glycol (PEG) hydrogel developed as
      a slow release system or adsorbed to a deproteinized bovine bone matrix (DBBM), a
      clinically well-established bone substitute material. rhBMP-2 loaded materials
      were immersed in cell culture medium and rhBMP-2 concentration profiles in the
      supernatant were determined by an enzyme-linked immunosorbent assay. The
      corresponding biological activities were assessed in vitro by alkaline
      phosphatase activity assay. We show a strong affinity of rhBMP-2 for DBBM and
      reduced biological activity after its release from PEG hydrogels. Glycosylated
      rhBMP-2 was significantly less affected by the hydrogel and interacted
      significantly more strongly with DBBM than non-glycosylated rhBMP-2. We therefore
      question the combination of PEG hydrogels with DBBM as a rhBMP-2 delivery system
      over DBBM alone, since rhBMP-2 released from the hydrogel will be trapped by
      DBBM. Moreover, our results suggest that glycosylated rhBMP-2 is favorable in
      combination with PEG hydrogels, since its activity is better preserved, whereas
      in combination with DBBM non-glycosylated rhBMP-2 is favorable, benefiting from
      an initially higher concentration of free rhBMP-2.

PMID- 21867783
TI  - Proteomic and immunoproteomic analysis of Aggregatibacter actinomycetemcomitans
      JP2 clone strain HK1651.
AB  - The proteome of Aggregatibacter actinomycetemcomitans HK1651 (JP2 clone) and
      immunoreactive antigens were studied by two-dimensional (2D) gel electrophoresis,
      matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS),
      and 2D immunoblotting. The highly leukotoxic JP2 clone of A.
      actinomycetemcomitans is strongly associated with aggressive periodontitis (AgP)
      in adolescents of North-West African descent and the pathogenicity of this
      bacterium is of major interest. Hence, we developed a comprehensive 2D proteome
      reference map of A. actinomycetemcomitans proteins with 167 identified spots
      representing 114 different proteins of which 15 were outer membrane proteins. To
      unravel immunoreactive antigens, we applied 2D-gel and subsequent immunoblotting
      analyses using sera from five individuals with A. actinomycetemcomitans
      infections and one healthy control. The analysis revealed 32 immunoreactive
      proteins. Antibodies to two outer membrane proteins, YaeT (85 kDa) and Omp39 (39
      kDa), not previously described as immunoreactive, were found only in subjects
      with current or previous A. actinomycetemcomitans JP2 infection. Further proteome
      based studies of A. actinomycetemcomitans combined with analyses of the humoral
      immune response and targeted against outer membrane proteins may provide
      important insight into the host relationship of this important pathogen.

PMID- 21867784
TI  - Targeting metabolic pathways for genetic engineering abiotic stress-tolerance in
      crops.
AB  - Abiotic stress conditions are the major limitations in modern agriculture.
      Although many genes associated with plant response(s) to abiotic stresses have
      been indentified and used to generate stress tolerant plants, the success in
      producing stress-tolerant crops is limited. New technologies are providing
      opportunities to generate stress tolerant crops. Biotechnological approaches that
      emphasize the development of transgenic crops under conditions that mimic the
      field situation and focus on the plant reproductive stage will significantly
      improve the opportunities of producing stress tolerant crops. Here, we highlight
      recent advances and discuss the limitations that hinder the fast integration of
      transgenic crops into agriculture and suggest possible research directions. This
      article is part of a Special Issue entitled: Plant gene regulation in response to
      abiotic stress.

PMID- 21867785
TI  - AP2/ERF family transcription factors in plant abiotic stress responses.
AB  - In terrestrial environments, temperature and water conditions are highly
      variable, and extreme temperatures and water conditions affect the survival,
      growth and reproduction of plants. To protect cells and sustain growth under such
      conditions of abiotic stress, plants respond to unfavourable changes in their
      environments in developmental, physiological and biochemical ways. These
      responses require expression of stress-responsive genes, which are regulated by a
      network of transcription factors. The AP2/ERF family is a large family of plant
      specific transcription factors that share a well-conserved DNA-binding domain.
      This transcription factor family includes DRE-binding proteins (DREBs), which
      activate the expression of abiotic stress-responsive genes via specific binding
      to the dehydration-responsive element/C-repeat (DRE/CRT) cis-acting element in
      their promoters. In this review, we discuss the functions of the AP2/ERF-type
      transcription factors in plant abiotic stress responses, with special emphasis on
      the regulations and functions of two major types of DREBs, DREB1/CBF and DREB2.
      In addition, we summarise the involvement of other AP2/ERF-type transcription
      factors in abiotic stress responses, which has recently become clear. This
      article is part of a Special Issue entitled: Plant gene regulation in response to
      abiotic stress.

PMID- 21867786
TI  - Gene regulation in response to DNA damage.
AB  - To deal with different kinds of DNA damages, there are a number of repair
      pathways that must be carefully orchestrated to guarantee genomic stability. Many
      proteins that play a role in DNA repair are involved in multiple pathways and
      need to be tightly regulated to conduct the functions required for efficient
      repair of different DNA damage types, such as double strand breaks or DNA
      crosslinks caused by radiation or genotoxins. While most of the factors involved
      in DNA repair are conserved throughout the different kingdoms, recent results
      have shown that the regulation of their expression is variable between different
      organisms. In the following paper, we give an overview of what is currently known
      about regulating factors and gene expression in response to DNA damage and put
      this knowledge in context with the different DNA repair pathways in plants. This
      article is part of a Special Issue entitled: Plant gene regulation in response to
      abiotic stress.

PMID- 21867787
TI  - Public reporting of cardiac surgery performance: introduction.

PMID- 21867788
TI  - Public reporting of cardiac surgery performance: Part 2--implementation.
AB  - Appropriate implementation is essential to create a credible public reporting
      system. Ideally, data should be obtained from an audited clinical data registry,
      and structure, process, or outcomes metrics may be reported. Composite measures
      are increasingly used, as are measures of appropriateness, patient satisfaction,
      functional status, and health-related quality of life. Classification of provider
      performance should use statistical criteria appropriate to the policy objectives
      and to the desired balance of sensitivity and specificity. Public reports should
      use simplified visual or tabular presentation aids that maximize correct
      interpretation of numerical data. Because of sample size issues, and to emphasize
      that cardiac surgery requires team-based care, public reporting should generally
      be focused at the program rather than individual surgeon level. This may also
      help to mitigate risk aversion, the avoidance of high-risk patients.

PMID- 21867789
TI  - Public reporting of cardiac surgery performance: Part 1--history, rationale,
      consequences.
AB  - Cardiac surgical report cards have historically been mandatory. This paradigm
      changed when The Society of Thoracic Surgeons recently implemented a voluntary
      public reporting program based on benchmark analyses from its National Cardiac
      Database. The primary rationale is to provide transparency and accountability,
      thus affirming the fundamental ethical right of patient autonomy. Previous
      studies suggest that public reporting facilitates quality improvement, although
      other approaches such as confidential feedback of results and regional quality
      improvement initiatives are also effective. Public reporting has not
      substantially impacted patient referral patterns or market share. However, this
      may change with implementation of healthcare reform and with refinement of public
      reporting formats to enhance consumer interpretability. Finally, the potential
      unintended adverse consequences of public reporting must be monitored,
      particularly to assure that hospitals and surgeons remain willing to care for
      high-risk patients.

PMID- 21867792
TI  - Out of the frying pan into the fire--the P300-based BCI faces real-world
      challenges.
AB  - Brain-computer interfaces (BCIs) have been investigated for more than 20 years.
      Many BCIs use noninvasive electroencephalography as a measurement technique and
      the P300 event-related potential as an input signal (P300 BCI). Since the first
      experiment with a P300 BCI system in 1988 by Farwell and Donchin, not only data
      processing has improved but also stimuli presentation has been varied and a
      plethora of applications was developed and refined. Nowadays, these applications
      are facing the challenge of being transferred from the research laboratory into
      real-life situations to serve motor-impaired people in their homes as assistive
      technology.

PMID- 21867791
TI  - Making the lifetime connection between brain and machine for restoring and
      enhancing function.
AB  - A reliable neural interface that lasts a lifetime will lead to the development of
      neural prosthetic devices as well as the possibility that brain function can be
      enhanced. Our data demonstrate that a reliable neural interface is best achieved
      when the surrounding neuropil grows into the electrode tip where it is held
      securely, allowing myelinated axons to be recorded using implanted amplifiers.
      Stable single and multiunits were recorded from three implanted subjects and
      classified according to amplitudes and firing rates. In one paralyzed and mute
      subject implanted for over 5 years with a double electrode in the speech motor
      cortex, the single units allowed recognition of over half the 39 English language
      phonemes detected using a variety of decoding methods. These single units were
      used by the subject in a speech task where vowel phonemes were recognized and fed
      back to the subject using audio output. Weeks of training resulted in an 80%
      success rate in producing four vowels in an adaptation of the classic center-out
      task used in motor control studies. The importance of using single units was
      shown in a different task using pure tones that the same subject heard and then
      sung or hummed in his head. Feedback was associated with smoothly coordinated
      unit firings. The plasticity of the unit firings was demonstrated over several
      sessions first without, and then with, feedback. These data suggest that units
      can be reliably recorded over years, that there is an inverse relationship
      between single unit firing rate and amplitude, that pattern recognition decoding
      paradigms can allow phoneme recognition, that single units appear more important
      than multiunits when precision is important, and that units are plastic in their
      functional relationships. These characteristics of a reliable neural interface
      are essential for the development of neural prostheses and also for the future
      enhancement of human brain function.

PMID- 21867793
TI  - Toward a whole-body neuroprosthetic.
AB  - Brain-machine interfaces (BMIs) hold promise for the restoration of body mobility
      in patients suffering from devastating motor deficits caused by brain injury,
      neurological diseases, and limb loss. Considerable progress has been achieved in
      BMIs that enact arm movements, and initial work has been done on BMIs for lower
      limb and trunk control. These developments put Duke University Center for
      Neuroengineering in the position to develop the first BMI for whole-body control.
      This whole-body BMI will incorporate very large-scale brain recordings, advanced
      decoding algorithms, artificial sensory feedback based on electrical stimulation
      of somatosensory areas, virtual environment representations, and a whole-body
      exoskeleton. This system will be first tested in nonhuman primates and then
      transferred to clinical trials in humans.

PMID- 21867794
TI  - Biocompatible multichannel electrodes for long-term neurophysiological studies
      and clinical therapy--novel concepts and design.
AB  - Chronic neural interfaces that are both structurally and functionally stable
      inside the brain over long time periods and that have minimal effects on the
      physiological conditions of the neural tissue to be studied hold great promise to
      become invaluable research and clinical tool in the near future. In this chapter,
      I will briefly review the state of the art of neural interfaces and the concepts
      behind our recent research and development of ultrathin multichannel electrodes.

PMID- 21867795
TI  - Deep brain stimulation: BCI at large, where are we going to?
AB  - Brain-computer interfaces (BCIs) include stimulators, infusion devices, and
      neuroprostheses. They all belong to functional neurosurgery. Deep brain
      stimulators (DBS) are widely used for therapy and are in need of innovative
      evolutions. Robotized exoskeletons require BCIs able to drive up to 26 degrees of
      freedom (DoF). We report the nanomicrotechnology development of prototypes for
      new 3D DBS and for motor neuroprostheses. For this complex project, all compounds
      have been designed and are being tested. Experiments were performed in rats and
      primates for proof of concepts and development of the electroencephalogram (EEG)
      recognition algorithm. METHODS: Various devices have been designed. (A) In human,
      a programmable multiplexer connecting five tetrapolar (20 contacts) electrodes to
      one DBS channel has been designed and implanted bilaterally into STN in two
      Parkinsonian patients. (B) A 50-mm diameter titanium implant, telepowered,
      including a radioset, emitting ECoG data recorded by a 64-electrode array using
      an application-specific integrated circuit, is being designed to be implanted in
      a 50-mm trephine opening. Data received by the radioreceiver are processed
      through an original wavelet-based Iterative N-way Partial Least Square algorithm
      (INPLS, CEA patent). Animals, implanted with ECoG recording electrodes, had to
      press a lever to obtain a reward. The brain signature associated to the lever
      press (LP) was detected online by ECoG processing using INPLS. This detection
      allowed triggering the food dispenser. RESULTS: (A) The 3D multiplexer allowed
      tailoring the electrical field to the STN. The multiplication of the contacts
      affected the battery life and suggested different implantation schemes. (B) The
      components of the human implantable cortical BCI are being tested for reliability
      and toxicology to meet criteria for chronicle implantation in 2012. (C) In rats,
      the algorithm INPLS could detect the cortical signature with an accuracy of about
      80% of LPs on the electrodes with the best correlation coefficient (located over
      the cerebellar cortex), 1% of the algorithm decisions were false positives. We
      aim to pilot effectors with DoF up to 3 in monkeys. CONCLUSION: We have designed
      multielectrodes wireless implants to open the way for BCI ECoG-driven effectors.
      These technologies are also used to develop new generations of brain stimulators,
      either cortical or for deep targets. This chapter is aimed at illustrating that
      BCIs are actually the daily background of DBS, that the evolution of the method
      involves a growing multiplicity of targets and indications, that new technologies
      make possible and simpler than before to design innovative solutions to improve
      DBS methodology, and that the coming out of BCI-driven neuroprostheses for
      compensation of motor and sensory deficits is a natural evolution of functional
      neurosurgery.

PMID- 21867796
TI  - Deep brain stimulation emerging indications.
AB  - There are a number of emerging surgical indications for deep brain stimulation.
      We have shown that modulation of activity within motor, mood, and cognitive
      circuits has beneficial effects in patients with Parkinson's disease, treatment
      resistant depression, and perhaps Alzheimer's type dementia. We review the
      rationale, safety, and efficacy for each of these indications, focusing on
      disease mechanisms and relevant data that are necessary to document therapeutic
      value in each case. The review closes with some thoughts on possible future
      directions for deep brain stimulation. It is likely that applications for deep
      brain stimulation will continue to expand as accumulating data establish its
      safety and efficacy profile in these and other conditions.

PMID- 21867797
TI  - Development of neuromodulation treatments in a large animal model--do
      neurosurgeons dream of electric pigs?
AB  - The Gottingen minipig has been established as a translational research animal for
      neurological and neurosurgical disorders. This animal has a large gyrencephalic
      brain suited for examination at sufficient resolution with conventional clinical
      scanning modalities. The large brain, further, allows use of standard
      neurosurgical techniques and can accommodate clinical neuromodulatory devises
      such as deep brain stimulation (DBS) electrodes and encapsulated cell biodelivery
      devices making the animal ideal for basic scientific studies on neuromodulation
      mechanisms and preclinical tests of new neuromodulation technology for human use.
      The use of the Gottingen minipig is economical and does not have the concerns of
      the public associated with the experimental use of primates, cats, and dogs, thus
      providing a cost-effective research model for translation of rodent data before
      clinical trials are initiated.

PMID- 21867798
TI  - A few examples of the contribution of animal research in rodents for clinical
      application of deep brain stimulation.
AB  - In the late 1980s, deep brain stimulation has regained interest for the treatment
      of neurological disorders. The first spectacular application has been developed
      for the treatment of Parkinson's disease. This development has been the result of
      interactions between clinical observations and studies carried out in animal
      models. Further investigations in animal models have lead to consider not only
      possible side effects of DBS on nonmotor functions in parkinsonian patients but
      also DBS as a possible strategy for other diseases, including psychiatric
      disorders such as obsessive compulsive disorder or addiction.

PMID- 21867800
TI  - Multimodal, longitudinal assessment of intracortical microstimulation.
AB  - The fundamental obstacle to neuroprostheses based on penetrating microstimulation
      is the tissue's response to the device insertion and to the application of the
      electrical stimulation. Our long-term goal is to develop multichannel
      microstimulation of central nervous tissue for clinical therapy. The overall
      objective of this research is to identify the optimal parameters for a
      chronically implanted microstimulation device. In particular, the work presented
      here focuses on the effects of repeated stimulation and the reactive tissue
      response on the efficacy of stimulation-driven behavior. To this end,
      psychophysical experiments were performed using multichannel cortical implants in
      the auditory cortex of rats. Further, we investigated the effect of the device
      tissue interfacial quality on the psychophysical threshold. Here, we report the
      effects of cortical depth, days postimplant on the psychophysical threshold of
      auditory cortical microstimulation, along with correlated impedance spectral
      changes and post vivo histology. We expect that these data will further enable
      neuroprosthetic development.

PMID- 21867799
TI  - Cochlear implants matching the prosthesis to the brain and facilitating desired
      plastic changes in brain function.
AB  - The cochlear implant (CI) is one of the great success stories of modern medicine.
      A high level of function is provided for most patients. However, some patients
      still do not achieve excellent or even good results using the present-day
      devices. Accumulating evidence is pointing to differences in the processing
      abilities of the "auditory brain" among patients as a principal contributor to
      this remaining and still large variability in outcomes. In this chapter, we
      describe a new approach to the design of CIs that takes these differences into
      account and thereby may improve outcomes for patients with compromised auditory
      brains.

PMID- 21867801
TI  - The functional consequences of chronic, physiologically effective intracortical
      microstimulation.
AB  - Many studies have demonstrated the ability of chronically implanted
      multielectrode arrays (MEAs) to extract information from the motor cortex of both
      humans and nonhuman primates. Similarly, many studies have shown the ability of
      intracortical microstimulation to impart information to the brain via a single or
      a few electrodes acutely implanted in sensory cortex of nonhuman primates, but
      relatively few microstimulation studies characterizing chronically implanted MEAs
      have been performed. Additionally, device and tissue damage have been reported at
      the levels of microstimulation used in these studies. Whether the damage
      resulting from microstimulation impairs the ability of MEAs to chronically
      produce physiological effects, however, has not been directly tested. In this
      study, we examined the functional consequences of multiple months of periodic
      microstimulation via chronically implanted MEAs at levels capable of evoking
      physiological responses, that is, electromyogram (EMG) activity. The
      functionality of the MEA and neural tissue was determined by measuring
      impedances, the ability of microstimulation to evoke EMG responses, and the
      recording of action potentials. We found that impedances and the number of
      recorded action potentials followed the previously reported trend of decreasing
      over time in both animals that received microstimulation and those which did not
      receive microstimulation. Despite these trends, the ability to evoke EMG
      responses and record action potentials was retained throughout the study. The
      results of this study suggest that intracortical microstimulation via MEAs did
      not cause functional failure, suggesting that MEA-based microstimulation is ready
      to transition into subchronic (< 30 days) human trials to determine whether
      complex spatiotemporal sensory percepts can be evoked by patterned
      microstimulation.

PMID- 21867802
TI  - Reducing surface area while maintaining implant penetrating profile lowers the
      brain foreign body response to chronically implanted planar silicon
      microelectrode arrays.
AB  - A consistent feature of the foreign body response (FBR), irrespective of the type
      of implant, is persistent inflammation at the biotic-abiotic interface signaled
      by biomarkers of macrophage/microglial activation. Since macrophage-secreted
      factors shape the foreign body reaction, implant designs that reduce macrophage
      activation should improve biocompatibility and, with regard to recording devices,
      should improve reliability and longevity. At present, it is unclear whether the
      goal of seamless integration is possible or whether electrode developers can
      modulate specific aspects of the FBR by intentionally manipulating the
      constitutive properties of the implant. To explore this area, we studied the
      chronic brain FBR to planar solid silicon microelectrode arrays and planar
      lattice arrays with identical penetrating profiles but with reduced surface area
      in rats after an 8-week indwelling period. Using quantitative
      immunohistochemistry, we found that presenting less surface area after equivalent
      iatrogenic injury is accompanied by significantly less persistent macrophage
      activation, decreased blood brain barrier leakiness, and reduced neuronal cell
      loss. Our findings show that it is possible for implant developers to modulate
      specific aspects of the FBR by intentionally manipulating the constitutive
      properties of the implant. Our results also support the theory that the FBR to
      implanted electrode arrays, and likely other implants, can be explained by the
      presence of macrophages at the biotic-abiotic interface, which act as a sustained
      delivery source of bioactive agents that diffuse into the adjacent tissue and
      shape various features of the brain FBR. Further, our findings suggest that one
      method to improve the recording consistency and lifetime of implanted
      microelectrode arrays is to design implants that reduce the amount of macrophage
      activation at the biotic-abiotic interface and/or enhance the clearance or impact
      of their released factors.

PMID- 21867803
TI  - Can histology solve the riddle of the nonfunctioning electrode? Factors
      influencing the biocompatibility of brain machine interfaces.
AB  - Neural interfaces hold great promise to become invaluable clinical and diagnostic
      tools in the near future. However, the biocompatibility and the long-term
      stability of the implanted interfaces are far from optimized. There are several
      factors that need to be addressed and standardized when improving the long-term
      success of an implanted electrode. We have chosen to focus on three key factors
      when evaluating the evoked tissue responses after electrode implantation into the
      brain: implant size, fixation mode, and evaluation period. Further, we show
      results from an ultrathin multichannel wire electrode that has been implanted in
      the rat cerebral cortex for 1 year. To improve biocompatibility of implanted
      electrodes, we would like to suggest that free-floating, very small, flexible,
      and, in time, wireless electrodes would elicit a diminished cell encapsulation.
      We would also like to suggest standardized methods for the electrode design, the
      electrode implantation method, and the analyses of cell reactions after
      implantation into the CNS in order to improve the long-term success of implanted
      neural interfaces.

PMID- 21867804
TI  - Changes in CNS structures after spinal cord lesions implications for BMI.
AB  - It is well established that a spinal circuitry can generate locomotor movements
      of the hindlimbs in absence of descending supraspinal inputs. This is based,
      among others, on the observation that after a complete spinalization, cats can
      walk with the hindlimbs on a treadmill. Does this spinal pattern generator (CPG)
      also participate in the recovery of locomotion after a partial spinal cord lesion
      (SCI)? After such SCI, functional reorganization can occur spontaneously along
      the whole neuraxis, namely the spinal cord circuitry below the lesion (CPG) and
      in supraspinal structures still partially connected to the spinal cord. This
      review focuses mainly on the capacity of the spinal and supraspinal structures to
      reorganize spontaneously after incomplete SCI in animals (rats and cats). BMI
      approaches to foster recovery of functions after various types of SCI should take
      into account these changes at the various levels of the CNS.

PMID- 21867805
TI  - Modeling the potentiality of spinal-like circuitry for stabilization of a planar
      arm system.
AB  - The design of control systems for limb prostheses seems likely to benefit from an
      understanding of how sensorimotor integration is achieved in the intact system.
      Traditional BMIs guess what movement parameters are encoded by brain activity and
      then decode them to drive prostheses directly. Modeling the known structure and
      emergent properties of the biological decoder itself is likely to be more
      effective in bridging from normal brain activity to functionally useful limb
      movement. In this study, we have extended a model of spinal circuitry (termed SLR
      for spinal-like regulator; see Raphael, G., Tsianos, G. A., & Loeb G. E. 2010,
      Spinal-like regulator facilitates control of a two-degree-of-freedom wrist. The
      Journal of Neuroscience, 30(28), 9431-9444.) to a planar elbow-shoulder system to
      investigate how the spinal cord contributes to the control of a musculoskeletal
      system with redundant and multiarticular musculature and interaction (Coriolis)
      torques, which are common control problems for multisegment linkages throughout
      the body. The SLR consists of a realistic set of interneuronal pathways
      (monosynaptic Ia-excitatory, reciprocal Ia-inhibitory, Renshaw inhibitory, Ib
      inhibitory, and propriospinal) that are driven by unmodulated step commands with
      learned amplitudes. We simulated the response of a planar arm to a brief, oblique
      impulse at the hand and investigated the role of cocontraction in learning to
      resist it. Training the SLR without cocontraction led to generally poor
      performance that was significantly worse than training with cocontraction.
      Further, removing cocontraction from the converged solutions and retraining the
      system achieved better performance than the SLR responses without cocontraction.
      Cocontraction appears to reshape the solution space, virtually eliminating the
      probability of entrapment in poor local minima. The local minima that are entered
      during learning with cocontraction are favorable starting points for learning to
      perform the task when cocontraction is abruptly removed. Given the control
      system's ability to learn effectively and rapidly, we hypothesize that it will
      generalize more readily to the wider range of tasks that subjects must learn to
      perform, as opposed to BMIs mapped to outputs of the musculoskeletal system.

PMID- 21867806
TI  - Advances in the use of electrical stimulation for the recovery of motor function.
AB  - This chapter sheds light on several issues that are being explored to optimize
      the application of electrical stimulation in a motor neural prosthesis (MNP) for
      the restoration of movement in humans with paralysis. Although several MNPs are
      commercially available, there are issues that limit their use in therapy and/or
      daily assistance: (1) the users' intention of what and how to move needs to be
      effectively transmitted to the MNP controller; (2) interface to the neural
      pathways that leads to physiological-like activation should be improved; (3)
      artificial control of the MNP should match the biological control of the
      preserved biological systems; and (4) sensors information should be fused and
      provided to both the controller of the MNP and the user. We suggest that with the
      improved use of cortical or other physiological signals, application of multipad
      electrodes with special protocols, rule-based control that mimics biological
      control, and with the incorporation of micro- and nanotechnologies, wireless
      communications, and microcontrollers, the MNP operation can be greatly enhanced.
      The chapter specifically addresses the control of MNP for the upper extremities
      and provides details on the new surface multipad electrodes that are of interest
      for neurorehabilitation of stroke patients.

PMID- 21867807
TI  - Intraspinal microstimulation for the recovery of function following spinal cord
      injury.
AB  - Spinal cord injury is a devastating neurological trauma, often resulting in the
      impairment of bladder, bowel, and sexual function as well as the loss of
      voluntary control of muscles innervated by spinal cord segments below the lesion
      site. Research is ongoing into several classes of therapies to restore lost
      function. These include the encouragement of neural sparing and regeneration of
      the affected tissue, and the intervention with pharmacological and rehabilitative
      means to improve function. This review will focus on the application of
      electrical current in the spinal cord in order to reactivate extant circuitry
      which coordinates and controls smooth and skeletal muscle below the injury. We
      first present a brief historical review of intraspinal microstimulation (ISMS)
      focusing on its use for restoring bladder function after spinal cord injury as
      well as its utilization as a research tool for mapping spinal cord circuits that
      coordinate movements. We then present a review of our own results related to the
      use of ISMS for restoring standing and walking movements after spinal cord
      injury. We discuss the mechanisms of action of ISMS and how they relate to
      observed functional outcomes in animal models. These include the activation of
      fibers-in-passage which lead to the transsynaptic spread of activation through
      the spinal cord and the ability of ISMS to produce fatigue-resistant, weight
      bearing movements. We present our thoughts on the clinical potential for ISMS
      with regard to implantation techniques, stability, and damage induced by
      mechanical and electrical factors. We conclude by suggesting improvements in
      materials and techniques that are needed in preparation for a clinical proof-of
      principle and review our current attempts to achieve these.

PMID- 21867808
TI  - Interfacing neurons with carbon nanotubes: (re)engineering neuronal signaling.
AB  - Carbon nanotubes (CNTs) are cylindrically shaped nanostructures made by sheets of
      graphene rolled up to form hollow tubes. Owing to their unique range of thermal,
      electronic, and structural properties, CNTs have been rapidly developing as a
      technology platform for biological and medical applications, including those
      designed to develop novel neuro-implantable devices. Depending on their
      structure, CNTs combine an incredible strength with an extreme flexibility.
      Further, these materials exhibit physical and chemical properties which allow
      them to efficiently conduit electrical current in electrochemical interfaces.
      CNTs can be organized in scaffolds made up of small fibers or tubes with
      diameters similar to those of neural processes such as axons and dendrites.
      Recently, CNT scaffolds have been found to promote growth, differentiation, and
      survival of neurons and to modify their electrophysiological properties. These
      features make CNTs an attractive material for the design of nano-bio hybrid
      systems able to govern cell-specific behaviors in cultured neuronal networks. The
      leading scope of this short review is to highlight how nanotube scaffolds can
      impact on neuronal signaling ability. In particular, we will focus on the direct
      and specific interactions between this synthetic nanomaterial and biological cell
      membranes, and on the ability of CNTs to improve interfaces developed to record
      or to stimulate neuronal activity. CNTs hold the potential for the development of
      innovative nanomaterial-based neurological implants. Therefore, it is
      particularly relevant to improve our knowledge on the impact on neuronal
      performance of interfacing nerve cells with CNTs.

PMID- 21867809
TI  - Nanomodified surfaces and neurite outgrowth.
AB  - Here we describe our attempts to study the interaction of nanomodified surfaces
      with neurons and macrophages. Surfaces with nano-sized topographies produced by
      UV lithography, electrochemical etching, nanoimprint lithography,
      microdispensing, or by electrospinning of plastic nanofibers or by making plastic
      replicas of the extracellular matrix with nanoresolution were found to guide
      neurite outgrowth extending from the dorsal root and the superior cervical
      ganglion in tissue culture. Ordered arrays of nanowires acted as particularly
      potent guides for the neurites. Loose nanowires activated the macrophages. We
      conclude that relatively simple nanomodifications of surfaces can be utilized to
      guide neurites. This property could potentially be applied to guide neurite
      outgrowth on implants in the nervous system intended for recordings of electrical
      and/or chemical activities.

PMID- 21867810
TI  - Direct local polymerization of poly(3,4-ethylenedioxythiophene) in rat cortex.
AB  - Glial scar encapsulation is thought to be one of the major reasons for the
      failure of chronic brain-machine interfaces. Many strategies, including
      modification of the probe surface chemistry, delivery of anti-inflammatory drugs,
      and changes of probe geometry, have been employed to reduce glial scar formation.
      We have proposed that a possible means to establish long-term, reliable
      communication across the scar is the in situ polymerization of conjugated
      polymers such as PEDOT in neural tissue. Previously, we exposed entire brain
      slices to the EDOT monomer. Here, we demonstrate that PEDOT can be polymerized by
      the direct delivery of EDOT monomer to the reaction site. The monomer was
      delivered into rat cortex via microcannula and simultaneously electrochemically
      polymerized within the tissue using a microwire electrode. We found that the
      resulting PEDOT polymer cloud grew out from the working electrode tip and
      extended far out into the brain tissue, spanning distances more than 1mm. We also
      examined the morphology of resulting polymer cloud by optical microscopy.

PMID- 21867811
TI  - Respiratory tract infections: advances in diagnosis, management and prevention.

PMID- 21867812
TI  - New diagnostic tests for pneumonia: what is their role in clinical practice?
AB  - The utility of diagnostic studies to determine the etiologic agents of community
      acquired pneumonia has been controversial in part because of the lack of rapid,
      accurate, easily performed, and cost-effective methods. Advancements in molecular
      testing methods and biological markers are becoming available with marked
      expansion of diagnostic capability for infectious diseases. Subsequent studies
      and clinical experience will clarify their real clinical value.

PMID- 21867814
TI  - Optimizing antibiotic pharmacodynamics in hospital-acquired and ventilator
      acquired bacterial pneumonia.
AB  - Nosocomial pneumonia carries a high morbidity and mortality and creates a large
      burden on health care use. As resistance to currently available antibiotics
      continues to increase, the role of pharmacodynamics in drug regimen optimization
      becomes pivotal to the clinical success of patient therapy. This article reviews
      the evidence behind pharmacodynamic optimization including the use of Monte Carlo
      simulations, changes in pharmacokinetic parameters of critically ill patients,
      and differing strategies to optimize drug regimens. Emphasis is placed on drugs
      used to treat hospital-acquired and ventilator-acquired pneumonia, and programs
      implementing pharmacodynamic optimization are highlighted.

PMID- 21867813
TI  - Biomarkers to optimize antibiotic therapy for pneumonia due to multidrug
      resistant pathogens.
AB  - No currently available biomarker can be used as a diagnostic marker for
      ventilator-associated pneumonia due to multidrug-resistant pathogens.
      Procalcitonin can be used to customize the duration of antimicrobial treatment
      without excess morbidity and mortality: when its concentration is less than 0.5
      ng/mL or has decreased by 80% or more compared with the peak concentration,
      antibiotics can be stopped. With this strategy, extreme vigilance must be
      maintained after terminating antimicrobial therapy to detect a recurrent
      infection.

PMID- 21867815
TI  - Epidemic viral pneumonia and other emerging pathogens.
AB  - Viruses cause a high percentage of community-acquired pneumonias. The advent of
      polymerase chain reaction and other molecular techniques has been associated with
      the detection of a higher prevalence of common respiratory viruses than
      previously suspected. Better diagnostics have shown new viral pathogens regularly
      in epidemics, immunocompromised patients, and occasionally children. Despite
      better diagnostics, treatment for all but influenza is still very limited.

PMID- 21867817
TI  - The use of large databases to study pneumonia: what is their value?
AB  - A large pneumonia database can be defined as one containing more than 1000
      patients. Important strengths of large databases include the ability to evaluate
      infrequent predictor or outcome variables, and increased generalizability. Beyond
      analysis of the database core study, large databases facilitate secondary
      analysis, expansion with ancillary studies, and concurrent analysis with other
      databases. Computer technology is now available that is able to merge sizable
      databases with the objective to generate a very large database. Construction of a
      global, very large pneumonia database is an achievable goal that can move
      clinical research in pneumonia to a higher level.

PMID- 21867816
TI  - Defining severe pneumonia.
AB  - Pneumonia is an important clinical and public health problem. Identification and
      prediction of severe pneumonia are significant concerns. Attempts to define
      severe pneumonia should recognize that different purposes are served by different
      definitions; no single definition meets all needs. At present, several prediction
      models have been proposed or validated. Biomarkers are not yet ready for routine
      use. The authors recommend careful consideration of the implications of any given
      definition of pneumonia severity. Outcome studies are needed to integrate human
      and health care system factors with the application of pneumonia severity
      definitions.

PMID- 21867818
TI  - The impact of guidelines on the outcomes of community-acquired and ventilator
      associated pneumonia.
AB  - The correct implementation of the current guidelines for the management of
      community-acquired pneumonia is associated with less mortality, faster clinical
      stabilization, and lower costs in these patients. By contrast, implementing the
      current guidelines for the management of hospital-acquired pneumonia has been
      followed by an increase in initially adequate antibiotic treatment but has not
      been accompanied by a consistently improved outcome in patients.

PMID- 21867819
TI  - Healthcare-associated pneumonia: approach to management.
AB  - Healthcare-associated pneumonia patients have worse outcomes and a different
      microbiologic profile than those with community-acquired pneumonia, including a
      greater risk for multidrug-resistant (MDR) organism infection. Risks include
      hospitalization for 2 or more days within 90 days, presentation from a nursing
      home or long-term care facility, attending a hospital or hemodialysis clinic,
      receiving intravenous therapy within 30 days, and immunosuppression. Ability to
      predict infection with MDR organisms varies, and the relative frequency of MDR
      organisms varies by geographic region. Initial treatment is broad-spectrum
      empiric antibiotics.

PMID- 21867820
TI  - De-escalation therapy: is it valuable for the management of ventilator-associated
      pneumonia?
AB  - In therapy for ventilator-associated pneumonia, it is essential to get initial
      empiric therapy correct; this is challenging because many patients are infected
      with multidrug-resistant pathogens. The need for achieving appropriate therapy
      can lead to broad-spectrum empiric therapy, which can represent antibiotic
      overuse and promote even more resistance. In an effort to combat this problem, de
      escalation therapy has been proposed, with the goals of reducing the number of
      drugs, the spectrum of therapy, and the duration of therapy. This review examines
      the factors associated with an effective de-escalation strategy and ways to
      increase the rates of de-escalation in the future.

PMID- 21867821
TI  - Bronchiectasis: new approaches to diagnosis and management.
AB  - Non-cystic fibrosis (CF) bronchiectasis is a common, potentially serious,
      condition. Further investigations should be performed in an attempt to identify
      the underlying cause because it may lead to a change in therapy and have
      significant prognostic implications. MRI is being investigated as a radiation
      free alternative to high-resolution CT scan of the chest. Many of the treatment
      recommendations for non-CF bronchiectasis have not been studied in randomized
      controlled trials but have been extrapolated from the management recommendations
      for CF. Studies are beginning to inform decisions regarding the management of non
      CF bronchiectasis, and an understanding of the best treatment options is
      beginning to emerge.

PMID- 21867822
TI  - Diagnosis of ventilator-associated respiratory infections (VARI): microbiologic
      clues for tracheobronchitis (VAT) and pneumonia (VAP).
AB  - Intubated patients are at risk of bacterial colonization and ventilator
      associated respiratory infection (VARI). VARI includes tracheobronchitis (VAT) or
      pneumonia (VAP). VAT and VAP caused by multidrug-resistant (MDR) pathogens are
      increasing in the United States and Europe. In patients with risk factors for MDR
      pathogens, empiric antibiotics are often initiated for 48 to 72 hours pending the
      availability of pathogen identification and antibiotic sensitivity data.
      Extensive data indicate that early, appropriate antibiotic therapy improves
      outcomes for patients with VAP. Recognizing and treating VARI may allow earlier
      appropriate therapy and improved patient outcomes.

PMID- 21867823
TI  - Aerosolized antibiotics in the intensive care unit.
AB  - This review summarizes recent clinical data examining the use of aerosolized
      antimicrobial therapy for the treatment of respiratory tract infections in
      mechanically ventilated patients in the intensive care unit. Aerosolized
      antibiotics provide high concentrations of drug in the lung without the systemic
      toxicity associated with the intravenous antibiotics. First introduced in the
      1960s as a treatment of tracheobronchitis and bronchopneumonia caused by
      Pseudomonas aeruginosa, now, more than 40 years later, there is a resurgence of
      interest in using this mode of delivery as a primary therapy for ventilator
      associated tracheobronchitis and an adjunctive therapy for ventilator-associated
      pneumonia.

PMID- 21867824
TI  - Should management of pneumonia be an indicator of quality of care?
AB  - Many regulatory bodies and payers measure the quality of care provided to
      patients admitted to the hospital with pneumonia. Some pneumonia quality measures
      were not based on high-level evidence, and there is also concern that public
      reporting of performance could drive excessive use of diagnostic testing and
      antibiotic treatment. There have been significant increases in the performance
      rate of several process of care recommended for patients hospitalized with
      pneumonia, accompanied by a decrease in 30-day mortality. To maximize the
      potential for improved patient outcomes, physicians and regulators must remain
      vigilant to detect unintended negative consequences related to performance
      measurement.

PMID- 21867825
TI  - Prevention of VAP: is zero rate possible?
AB  - Infection prevention measures, specifically targeting ventilator-associated
      pneumonia (VAP), have been purposed as quality-of-care indicators for patients in
      intensive care units. The authors discuss some of the recent evidence of the
      prevention of nosocomial infections, with a particular emphasis on VAP. Moreover,
      there are several pitfalls in considering VAP rates as a safety indicator.
      Because of these limitations, the authors recommend the use of specific process
      measures, designed to reduce VAP, as the basis for interinstitutional
      benchmarking.

PMID- 21867826
TI  - Oral and maxillofacial health care delivery and the American College of Surgeons:
      a call to action.

PMID- 21867827
TI  - A response to Dr Dennis on predoctoral dental education and the future of oral
      and maxillofacial surgery.

PMID- 21867828
TI  - Comparative evaluation of vertical body osteotomy and sagittal split osteotomy
      for mandibular corpus distraction: is there a rationale for the new technique?

PMID- 21867831
TI  - Incremental diagnostic value of magnetic resonance imaging in the
      characterization of a cardiac mass.

PMID- 21867832
TI  - Implantation-related complications of implantable cardioverter-defibrillators and
      cardiac resynchronization therapy devices: a systematic review of randomized
      clinical trials.
AB  - The number of implantable cardioverter-defibrillator (ICD) and cardiac
      resynchronization therapy (CRT) implantations is increasing drastically
      worldwide, and hence, the number of implanting centers is also increasing.
      Despite abundant data on the beneficial effect of these devices, little is known
      regarding safety and complication rates. Eleven ICD and 7 CRT trials were
      systematically reviewed to provide data on the frequency of in-hospital mortality
      and complications related to the implantation. Average in-hospital mortality was
      2.7% in trials using both thoracotomy and nonthoracotomy ICDs, 0.2% in trials
      using nonthoracotomy ICDs, and 0.3% in CRT trials. The pneumothorax rate was
      similar between the nonthoracotomy ICD and CRT trials (0.9%) Coronary sinus
      complications occurred in 2.0% of patients undergoing CRT. Lead dislodgement
      rates were higher in CRT trials (5.7%) than in nonthoracotomy ICD trials (1.8%).

PMID- 21867833
TI  - 16-year trends in the infection burden for pacemakers and implantable
      cardioverter-defibrillators in the United States 1993 to 2008.
AB  - OBJECTIVES: We analyzed the infection burden associated with the implantation of
      cardiac implantable electrophysiological devices (CIEDs) in the United States for
      the years 1993 to 2008. BACKGROUND: Recent data suggest that the rate of
      infection following CIED implantation may be increasing. METHODS: The Nationwide
      Inpatient Sample (NIS) discharge records were queried between 1993 and 2008 using
      the 9th Revision of the International Classification of Diseases (ICD-9-CM). CIED
      infection was defined as either: 1) ICD-9 code for device-related infection
      (996.61) and any CIED procedure or removal code; or 2) CIED procedure code along
      with systemic infection. Patient health profile was evaluated by coding for renal
      failure, heart failure, respiratory failure, and diabetes mellitus. The infection
      burden and patient health profile were calculated for each year, and linear
      regression was used to test for changes over time. RESULTS: During the study
      period (1993 to 2008), the incidence of CIED infection was 1.61%. The annual rate
      of infections remained constant until 2004, when a marked increase was observed,
      which coincided with an increase in the incidence of major comorbidities. This
      was associated with a marked increase in mortality and in-hospital financial
      charges. CONCLUSIONS: The infection burden associated with CIED implantation is
      increasing over time and is associated with prolonged hospital stays and high
      financial costs.

PMID- 21867834
TI  - Dual-chamber implantable cardioverter-defibrillator selection is associated with
      increased complication rates and mortality among patients enrolled in the NCDR
      implantable cardioverter-defibrillator registry.
AB  - OBJECTIVES: The aim of this study was to compare single- versus dual-chamber
      implantable cardioverter-defibrillator (ICD) implantation and complication rates
      in a large, real-world population. BACKGROUND: The majority of patients enrolled
      in ICD efficacy trials received single-chamber devices. Although dual-chamber
      ICDs offer theoretical advantages over single-chamber defibrillators, the
      clinical superiority of dual-chamber models has not been conclusively proven, and
      they may increase complications. METHODS: The National Cardiovascular Data
      Registry ICD Registry was used to examine the association between baseline
      characteristics and device selection in 104,049 patients receiving single- and
      dual-chamber ICDs between January 1, 2006, and December 31, 2007. A longitudinal
      cohort design was then used to determine in-hospital complication rates. RESULTS:
      Dual-chamber devices were implanted in 64,489 patients (62%). Adverse events were
      more frequent with dual-chamber than with single-chamber device implantation
      (3.17% vs. 2.11%, p < 0.001), as was the rate of in-hospital mortality (0.40% vs.
      0.23%, p < 0.001). After adjusting for demographics, medical comorbidities,
      diagnostic test data, and ICD indication, the odds of any complication (odds
      ratio: 1.40; 95% confidence interval: 1.28 to 1.52; p < 0.001) and in-hospital
      mortality (odds ratio: 1.45; 95% confidence interval: 1.20 to 1.74; p < 0.001)
      were increased with dual-chamber versus single-chamber ICD implantation.
      CONCLUSIONS: In this large, multicenter cohort of patients, dual-chamber ICD use
      was common. Dual-chamber device implantation was associated with increases in
      periprocedural complications and in-hospital mortality compared with single
      chamber defibrillator selection.

PMID- 21867835
TI  - Is less more? Dual- versus single-chamber implantable cardioverter
      defibrillators.

PMID- 21867836
TI  - Transcatheter aortic valve implantation in patients with severe aortic stenosis
      and small aortic annulus.
AB  - OBJECTIVES: Valve hemodynamics and clinical outcomes among patients with a small
      aortic annulus who underwent transcatheter aortic valve implantation (TAVI) were
      examined. BACKGROUND: The presence of a small aortic annulus may complicate the
      surgical management of patients with severe aortic stenosis (AS). TAVI is an
      alternative to aortic valve replacement (AVR) in high-risk patients, but few data
      exist on the results of TAVI in patients with a small aortic annulus. METHODS:
      Between 2007 and 2010, 35 patients (mean age 79.2 +/- 9.4 years) with severe AS
      and an aortic annulus diameter <20 mm (mean 18.5 +/- 0.9 mm) underwent TAVI with
      a 23-mm Edwards SAPIEN bioprosthesis (Edwards Lifesciences, Inc., Irvine,
      California). Echocardiographic parameters and clinical outcomes were assessed
      prior to discharge and at 6, 12, and 24 months. RESULTS: Procedural success was
      achieved in 34 patients (97.1%). There was 1 in-hospital death. Peak and mean
      transaortic gradients decreased from 76.3 +/- 33.0 mm Hg and 45.2 +/- 20.6 mm Hg
      at baseline to 21.8 +/- 8.4 mm Hg and 11.7 +/- 4.8 mm Hg post-procedure,
      respectively, both p < 0.0001. Mean indexed effective orifice area (IEOA)
      increased from 0.35 +/- 0.10 cm(2)/m(2) at baseline to 0.90 +/- 0.18 cm(2)/m(2)
      post-procedure, p < 0.0001. Severe prosthesis-patient mismatch (IEOA <0.65
      cm(2)/m(2)) occurred in 2 patients (5.9%). At a mean follow-up of 14 +/- 11
      months, gradients remained low and 30 of the 31 remaining survivors were in New
      York Heart Association functional class I or II. CONCLUSIONS: In high-risk
      patients with severe AS and a small aortic annulus, TAVI is associated with good
      post-procedural valve hemodynamics and clinical outcomes. TAVI may provide a
      reasonable alternative to conventional AVR in elderly patients with a small
      aortic annulus.

PMID- 21867837
TI  - Homocysteine and reclassification of cardiovascular disease risk.
AB  - OBJECTIVES: The purpose of this study was to examine whether adding homocysteine
      (Hcy) to a model based on traditional cardiovascular disease (CVD) risk factors
      improves risk classification. BACKGROUND: Data on using Hcy to reclassify
      individuals in various risk categories beyond traditional approaches have not
      been adequately scrutinized. METHODS: We performed a post hoc analysis of the
      MESA (Multi-Ethnic Study of Atherosclerosis) and NHANES III (National Health and
      Nutrition Examination Survey III) datasets. Hcy was used to predict composite CVD
      and hard coronary heart disease (CHD) events in the MESA study and CVD and CHD
      mortality in the NHANES III survey using adjusted Cox-proportional hazard
      analysis. Reclassification of CHD events was performed using a net
      reclassification improvement (NRI) index with a Framingham risk score (FRS) model
      with and without Hcy. RESULTS: Hcy level (>15 MUmol/l) significantly predicted
      CVD (adjusted hazard ratio [aHR]: 1.79, 95% confidence intervals [CI]: 1.19 to
      1.95; p = 0.006) and CHD events (aHR: 2.22, 95% CI: 1.20 to 4.09; p = 0.01) in
      the MESA trial and CVD (aHR: 2.72, 95% CI: 2.01 to 3.68; p < 0.001) and CHD
      mortality (aHR: 2.61, 95% CI: 1.83 to 3.73; p < 0.001) in the NHANES III, after
      adjustments for traditional risk factors and C-reactive protein. The level of
      Hcy, when added to FRS, significantly reclassified 12.9% and 18.3% of the overall
      and 21.2% and 19.2% of the intermediate-risk population from the MESA and NHANES
      cohorts, respectively. The categoryless NRI also showed significant
      reclassification in both MESA (NRI: 0.35, 95% CI: 0.17 to 0.53; p < 0.001) and
      NHANES III (NRI: 0.57, 95% CI: 0.43 to 0.71; p < 0.001) datasets. CONCLUSIONS:
      From these 2 disparate population cohorts, we found that addition of Hcy level to
      FRS significantly improved risk prediction, especially in individuals at
      intermediate risk for CHD events.

PMID- 21867838
TI  - Homocysteine and cardiovascular risk an old foe creeps back.

PMID- 21867839
TI  - Outcomes in patients with symptomatic cerebrovascular disease undergoing heart
      transplantation.
AB  - OBJECTIVES: We sought to determine outcomes in patients with and without
      symptomatic cerebrovascular disease (sCVD) undergoing heart transplantation.
      Second, we sought to determine factors associated with stroke in the
      perioperative period after heart transplantation. BACKGROUND: sCVD is considered
      a relative contraindication to heart transplantation. Despite this concern,
      outcomes in patients with sCVD undergoing heart transplantation have not been
      well defined. METHODS: Data on all single-organ heart transplants performed in
      the United States between April 1994 and December 2006 in patients age 40 years
      or older were analyzed. Survival analysis was performed to examine the effect of
      sCVD on the combined outcome of stroke or death, stroke, death, and functional
      decline, adjusting for potential confounding variables over long-term follow-up.
      In a separate analysis, predictors of perioperative stroke during the transplant
      related hospitalization were examined using multiple logistic regression.
      RESULTS: There were 1,078 patients with and 16,765 patients without sCVD. The
      annualized rates of stroke or death (11.5% vs. 7.8%; p < 0.001), stroke (4% vs.
      1.4%; p < 0.001), death (8.9% vs. 7.4%; p < 0.001), and functional decline (3.7%
      vs. 3.0%; p = 0.002) were higher in patients with sCVD than in patients without
      sCVD. In multivariable analysis, patients with sCVD were at increased risk of
      stroke or death (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.17 to
      1.42), stroke (HR: 2.24; 95% CI: 2.02 to 2.87), and functional decline (HR: 1.21;
      95% CI: 1.03 to 1.42) compared with those without sCVD. We did not identify a
      higher risk of death in patients with sCVD (HR: 1.08; 95% CI: 0.98 to 1.20),
      compared with those without sCVD. sCVD, ventilator use, and ventricular assist
      device use were the most important predictors of perioperative stroke.
      CONCLUSIONS: Patients with sCVD are at an increased risk of stroke and functional
      decline after transplantation independent of other variables, but not death,
      during long-term follow-up. These results should assist programs in making
      informed decisions in patients with sCVD who are undergoing evaluation for heart
      transplantation.

PMID- 21867840
TI  - Transplant complications: the lesser of 2 evils.

PMID- 21867841
TI  - Characterization of cardiac tumors in children by cardiovascular magnetic
      resonance imaging: a multicenter experience.
AB  - OBJECTIVES: The aim of this study was to report the results of an international
      multicenter experience of cardiac magnetic resonance imaging (MRI) evaluation of
      cardiac tumors in children, each with histology correlation or a diagnosis of
      tuberous sclerosis, and to determine which characteristics are predictive of
      tumor type. BACKGROUND: Individual centers have relatively little experience with
      diagnostic imaging of cardiac tumors in children, because of their low
      prevalence. The accuracy of cardiac MRI diagnosis on the basis of a pre-defined
      set of criteria has not been tested. METHODS: An international group of pediatric
      cardiac imaging centers was solicited for case contribution. Inclusion criteria
      comprised: 1) age at diagnosis <=18 years; 2) cardiac MRI evaluation of cardiac
      tumor; and 3) histologic diagnosis or diagnosis of tuberous sclerosis. Data from
      the cardiac MRI images were analyzed for mass characteristics. On the basis of
      pre-defined cardiac MRI criteria derived from published data, 3 blinded
      investigators determined tumor type, and their consensus diagnoses were compared
      with histologic diagnoses. RESULTS: Cases (n = 78) submitted from 15 centers in 4
      countries had the following diagnoses: fibroma (n = 30), rhabdomyoma (n = 14),
      malignant tumor (n = 12), hemangioma (n = 9), thrombus (n = 4), myxoma (n = 3),
      teratoma (n = 2), and paraganglioma, pericardial cyst, Purkinje cell tumor, and
      papillary fibroelastoma (n = 1, each). Reviewers who were blinded to the
      histologic diagnoses correctly diagnosed 97% of the cases but included a
      differential diagnosis in 42%. Better image quality grade and more complete
      examination were associated with higher diagnostic accuracy. CONCLUSIONS: Cardiac
      MRI can predict the likely tumor type in the majority of children with a cardiac
      mass. A comprehensive imaging protocol is essential for accurate diagnosis.
      However, histologic diagnosis remains the gold standard, and in some cases
      malignancy cannot be definitively excluded on the basis of cardiac MRI images
      alone.

PMID- 21867842
TI  - Cardiac magnetic resonance imaging signal characteristics of cardiac tumors in
      children.

PMID- 21867843
TI  - Midregion prohormone adrenomedullin and prognosis in patients presenting with
      acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial.
AB  - OBJECTIVES: The aim of this study was to determine the prognostic utility of
      midregion proadrenomedullin (MR-proADM) in all patients, cardiac and noncardiac,
      presenting with acute shortness of breath. BACKGROUND: The recently published
      BACH (Biomarkers in Acute Heart Failure) study demonstrated that MR-proADM had
      superior accuracy for predicting 90-day mortality compared with B-type
      natriuretic peptide (area under the curve: 0.674 vs. 0.606, respectively, p <
      0.001) in acute heart failure. METHODS: The BACH trial was a prospective, 15
      center, international study of 1,641 patients presenting to the emergency
      department with dyspnea. Using this dataset, the prognostic accuracy of MR-proADM
      was evaluated in all patients enrolled for predicting 90-day mortality with
      respect to other biomarkers, the added value in addition to clinical variables,
      as well as the added value of additional measurements during hospital admission.
      RESULTS: Compared with B-type natriuretic peptide or troponin, MR-proADM was
      superior for predicting 90-day all-cause mortality in patients presenting with
      acute dyspnea (c index = 0.755, p < 0.0001). Furthermore, MR-proADM added
      significantly to all clinical variables (all adjusted hazard ratios: >3.28), and
      it was also superior to all other biomarkers. MR-proADM added significantly to
      the best clinical model (bootstrap-corrected c index increase: 0.775 to 0.807;
      adjusted standardized hazard ratio: 2.59; 95% confidence interval: 1.91 to 3.50;
      p < 0.0001). Within the model, MR-proADM was the biggest contributor to the
      predictive performance, with a net reclassification improvement of 8.9%. Serial
      evaluation of MR-proADM performed in patients admitted provided a significant
      added value compared with a model with admission values only (p = 0.0005). More
      than one-third of patients originally at high risk could be identified by the
      biomarker evaluation at discharge as low-risk patients. CONCLUSIONS: MR-proADM
      identifies patients with high 90-day mortality and adds prognostic value to
      natriuretic peptides in patients presenting with acute shortness of breath.
      Serial measurement of this biomarker may also prove useful for monitoring,
      although further studies will be required. (Biomarkers in Acute Heart Failure
      [BACH]; NCT00537628).

PMID- 21867844
TI  - Low-density lipoprotein lowering does not improve calf muscle perfusion,
      energetics, or exercise performance in peripheral arterial disease.
AB  - OBJECTIVES: We hypothesized that low-density lipoprotein (LDL) reduction
      regardless of mechanism would improve calf muscle perfusion, energetics, or
      walking performance in peripheral arterial disease (PAD) as measured by magnetic
      resonance imaging and magnetic resonance spectroscopy. BACKGROUND: Statins
      improve cardiovascular outcome in PAD, and some studies suggest improved walking
      performance. METHODS: Sixty-eight patients with mild to moderate symptomatic PAD
      (age 65 +/- 11 years; ankle-brachial index [ABI] 0.69 +/- 0.14) were studied at
      baseline and annually for 2 years after beginning simvastatin 40 mg (n = 20) or
      simvastatin 40 mg/ezetimibe 10 mg (n = 18) if statin naive, or ezetimibe 10 mg (n
      = 30) if taking a statin. Phosphocreatine recovery time was measured by (31)P
      magnetic resonance spectroscopy immediately after symptom-limited calf exercise
      on a 1.5-T scanner. Calf perfusion was measured using first-pass contrast
      enhanced magnetic resonance imaging with 0.1 mM/kg gadolinium at peak exercise.
      Gadolinium-enhanced magnetic resonance angiography was graded. A 6-min walk and a
      standardized graded Skinner-Gardner exercise treadmill test with peak Vo(2) were
      performed. A repeated-measures model compared changes over time. RESULTS: LDL
      reduction from baseline to year 2 was greater in the simvastatin 40 mg/ezetimibe
      10 mg group (116 +/- 42 mg/dl to 56 +/- 21 mg/dl) than in the simvastatin 40 mg
      group (129 +/- 40 mg/dl to 90 +/- 30 mg/dl, p < 0.01). LDL also decreased in the
      ezetimibe 10 mg group (102 +/- 28 mg/dl to 79 +/- 27 mg/dl, p < 0.01). Despite
      this, there was no difference in perfusion, metabolism, or exercise parameters
      between groups or over time. Resting ABI did improve over time in the ezetimibe
      10 mg group and the entire study group of patients. CONCLUSIONS: Despite
      effective LDL reduction in PAD, neither tissue perfusion, metabolism, nor
      exercise parameters improved, although rest ABI did. Thus, LDL lowering does not
      improve calf muscle physiology or functional capacity in PAD. (Comprehensive
      Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

PMID- 21867845
TI  - Learning to walk before we run: the mechanics of medical intervention for
      peripheral arterial disease.

PMID- 21867846
TI  - Systolic murmur: a key to Pandora's box.

PMID- 21867847
TI  - Is reclassification of intermediate-risk subjects by coronary artery calcium
      scoring clinically useful?

PMID- 21867850
TI  - Ranolazine and silent ischemia.

PMID- 21867851
TI  - Clopidogrel after coronary artery bypass graft surgery: insufficient evidence.

PMID- 21867852
TI  - The unknown effect of clopidogrel resistance in dual antiplatelet therapies after
      coronary artery bypass grafting.

PMID- 21867854
TI  - A decade later.

PMID- 21867855
TI  - Transition of chronically ill youth to adult health care: experience of youth
      with hemoglobinopathy.
AB  - INTRODUCTION: The purpose of this study was to describe the transition
      experience, expectations, and concerns of chronically ill youth with
      hemoglobinopathy (CIYH) (e.g., sickle cell disease) who have transitioned to
      adult health care. METHOD: A descriptive phenomenological study was used to
      explore the transition experience of CIYH through interviews. A purposive sample
      of 14 CIYH aged 19 to 25 years were recruited from a large southwestern medical
      center. The Colaizzi method was used to analyze the CIYH's meaning of the
      transition experience. RESULTS: Themes identified were: Reactions to adult care
      transition ("I don't want to go"), concerns about transition experience ("What's
      going to happen to me?"), pushed into transitioning to adult care ("Facing the
      music"), and transitioned to adult care ("Accepting that I had to leave").
      DISCUSSION: The findings revealed CIYH's adjustment process, which may facilitate
      the design of effective interventions to provide uninterrupted medical care as
      the CIYH transitions to adult health care.

PMID- 21867856
TI  - Back pain in children: a holistic approach to diagnosis and management.
AB  - Back pain is a relatively common complaint presenting to the primary care
      practitioner and is addressed with increasing frequency in the pediatric
      literature. Back pain is not uncommon in adolescents and often is symptomatic of
      a relatively benign musculoskeletal etiology. Back pain in children less than 10
      years of age and most especially less than 4 years of age can signal a more
      alarming underlying condition. Evaluation requires a complete history including
      psychosocial and cultural considerations. Additionally a thorough clinical
      examination, strategic lab work and judicious imaging are imperative. Management
      and appropriate referral is specific to the underlying disease process. A
      holistic, individualized plan of care with inherent involvement of the child and
      parent/caregiver is essential to ensure safety and enhance outcomes.

PMID- 21867857
TI  - Parents' perceptions of their children's weight, eating habits, and physical
      activities at home and at school.
AB  - INTRODUCTION: Parental perceptions of their young children's weight and habits
      may play an important role in determining whether children develop and maintain
      healthy lifestyles. This study was conducted to determine perceptions of parents
      of third-grade children in an urban school setting regarding their children's
      weight, eating habits, and physical activities. METHODS: Parents anonymously
      completed surveys about their child's weight, eating habits, and daily
      activities. The survey also asked about how schools could encourage healthy
      eating and increased physical activity. RESULTS: Overall, 26% of the parents
      perceived their child to be overweight and expressed concern, but 40% of these
      parents believed that overweight is a condition that will be outgrown. Parents
      who reported eating more than eight meals per week with their child were less
      likely to report their child as overweight and more likely to believe that their
      child's physical activity level was appropriate. DISCUSSION: Most parents of
      third-grade students demonstrated concern regarding their child's weight and
      perceive obesity as a problem. Parents support school interventions such as
      nutrition education and fitness classes.

PMID- 21867858
TI  - Living with juvenile arthritis: adolescents' challenges and experiences.
AB  - INTRODUCTION: The objective of this study was to identify challenges that teens
      experience while living with juvenile arthritis (JA) from the perspective of
      youth and young adults with JA. METHOD: Focus group interviews were conducted
      with youth (aged 14-21 years) and young adults (aged 22-29 years) with JA using a
      semi-structured interview protocol that included questions about the challenges
      adolescents experience while living with arthritis. RESULTS: Challenges of living
      with JA were identified in the areas of (a) health care, (b) relationships, (c)
      school, (d) physical, and (e) individual. However, distinct perspectives emerged
      between youth and young adult participants. For youth, challenges were situated
      in present time and focused heavily on interpersonal situations. Alternatively,
      young adults reported challenges that illuminated their experiences of movement
      from adolescence into young adulthood (e.g., independently managing their JA and
      disclosure to dating partners). DISCUSSION: Findings from this study display
      complex and multifaceted experiences that teens face while living with arthritis.
      Experiences associated with arthritis were not limited to being described as
      health care-related challenges; rather, arthritis permeates multiple contexts in
      adolescents' lives.

PMID- 21867859
TI  - Outpatient management of community-associated methicillin-resistant
      Staphylococcus aureus skin and soft tissue infection.
AB  - During the past decade, there has been a dramatic increase in the number of
      patients presenting with skin and soft tissue infections in the outpatient
      setting. The predominant causative bacterium for these infections has recently
      been identified as community-associated methicillin-resistant Staphylococcus
      aureus (CA-MRSA). It is estimated that nearly 80% of infections caused by CA-MRSA
      manifest as skin and soft tissue infections which are of mild to modest severity.
      However, invasive disease and fatal illness has been reported among otherwise
      healthy adults and children. The rapid evolution of CA-MRSA presents a unique
      challenge for pediatric health care providers. As such, it is critical to raise
      awareness regarding the epidemiology, microbiology, and evidence-based treatment
      options for treating skin and soft tissue infections in the age of CA-MRSA. The
      aims of this article include discussion regarding the epidemiology, microbiology,
      and evidence-based management of CA-MRSA as well as publication of a more
      relevant one-page evidence-based treatment flow diagram and antimicrobial
      prescribing table for health care providers practicing in the ambulatory care
      setting.

PMID- 21867860
TI  - Intranasal fentanyl for pain management in children: a systematic review of the
      literature.
AB  - Intranasally administered fentanyl (INF) has been studied as an alternate route
      of delivery for pain relief in children. The purpose of this systematic review is
      to evaluate the available research evidence on the use of INF in the pediatric
      population. A search was conducted of PubMed, ISI, Scopus, Popline, CINAHL, and
      Embase for research studies evaluating INF in this population (0-18 years of
      age). The studies were graded on the strength of the evidence and the results
      reviewed. All of the reviewed studies showed similar or improved pain scores when
      compared with other opioids and administration methods. No severe adverse
      outcomes were reported. Current evidence suggests that INF is a safe and
      effective method of pain management for children in a variety of clinical
      settings.

PMID- 21867861
TI  - Herpes simplex virus reactivation and encephalitis after topectomy.

PMID- 21867862
TI  - Lead toxicity in a newborn.

PMID- 21867863
TI  - Management of acne vulgaris.

PMID- 21867864
TI  - Remembering the "Seven Rs": more ethical caveats for the PNP hospitalist.

PMID- 21867865
TI  - Evidence-based practice resources available on the internet.

PMID- 21867866
TI  - Research, innovation, translation, advocacy, standardization.

PMID- 21867867
TI  - Highlights of the 23nd Annual Scientific Sessions-a sonographer's perspective.

PMID- 21867868
TI  - Update on pediatric and congenital heart disease council activities and
      directions for the future.

PMID- 21867869
TI  - EAE/ASE recommendations for the use of echocardiography in new transcatheter
      interventions for valvular heart disease.
AB  - The introduction of devices for transcatheter aortic valve implantation, mitral
      repair, and closure of prosthetic paravalvular leaks has led to a greatly
      expanded armamentarium of catheter-based approaches to patients with regurgitant
      as well as stenotic valvular disease. Echocardiography plays an essential role in
      identifying patients suitable for these interventions and in providing intra
      procedural monitoring. Moreover, echocardiography is the primary modality for
      post-procedure follow-up. The echocardiographic assessment of patients undergoing
      trans-catheter interventions places demands on echocardiographers that differ
      from those of the routine evaluation of patients with native or prosthetic
      valvular disease. Consequently, the European Association of Echocardiography in
      partnership with the American Society of Echocardiography has developed the
      recommendations for the use of echocardiography in new transcatheter
      interventions for valvular heart disease. It is intended that this document will
      serve as a reference for echocardiographers participating in any or all stages of
      new transcatheter treatments for patients with valvular heart disease.

PMID- 21867870
TI  - Evaluation of aortic stenosis severity: new challenges, new solutions.

PMID- 21867871
TI  - Echocardiographic assessment of fabry cardiomyopathy: early diagnosis and follow
      up.

PMID- 21867872
TI  - What's in a name?

PMID- 21867873
TI  - Cadherins as matchmakers.
AB  - Cadherins implement afferent-target matching in invertebrates, but proof for this
      concept in mammalian circuits has remained elusive. Two new studies in this issue
      of Neuron show that cadherin-6 mediates retinal ganglion cell target selection
      and that cadherin-9 promotes synapse specificity in the hippocampus.

PMID- 21867874
TI  - The nodal origin of intrinsic bursting.
AB  - The output of cortical neurons in the form of bursts of action potentials was
      thought to be controlled solely by the dendrites. In this issue of Neuron,
      Maarten Kole reveals that axonal sodium channels at the first node of Ranvier are
      essential for neuronal burst firing.

PMID- 21867875
TI  - Memory time.
AB  - In this issue of Neuron, MacDonald et al. describe hippocampal "time cells" that
      fire during specific delay periods as rats performed a memory task. Converging
      results in monkeys suggest that the hippocampus encodes episodes by signaling
      events in time.

PMID- 21867876
TI  - From cradle to grave: the multiple roles of fibroblast growth factors in neural
      development.
AB  - The generation of a functional nervous system involves a multitude of steps that
      are controlled by just a few families of extracellular signaling molecules. Among
      these, the fibroblast growth factor (FGF) family is particularly prominent for
      the remarkable diversity of its functions. FGFs are best known for their roles in
      the early steps of patterning of the neural primordium and proliferation of
      neural progenitors. However, other equally important functions have emerged more
      recently, including in the later steps of neuronal migration, axon navigation,
      and synaptogenesis. We review here these diverse functions and discuss the
      mechanisms that account for this unusual range of activities. FGFs are essential
      components of most protocols devised to generate therapeutically important
      neuronal populations in vitro or to stimulate neuronal repair in vivo. How FGFs
      promote the development of the nervous system and maintain its integrity will
      thus remain an important focus of research in the future.

PMID- 21867877
TI  - Computational models of grid cells.
AB  - Grid cells are space-modulated neurons with periodic firing fields. In moving
      animals, the multiple firing fields of an individual grid cell form a triangular
      pattern tiling the entire space available to the animal. Collectively, grid cells
      are thought to provide a context-independent metric representation of the local
      environment. Since the discovery of grid cells in 2005, a number of models have
      been proposed to explain the formation of spatially repetitive firing patterns as
      well as the conversion of these signals to place signals one synapse downstream
      in the hippocampus. The present article reviews the most recent developments in
      our understanding of how grid patterns are generated, maintained, and
      transformed, with particular emphasis on second-generation computational models
      that have emerged during the past 2-3 years in response to criticism and new
      data.

PMID- 21867878
TI  - A transcriptomic atlas of mouse neocortical layers.
AB  - In the mammalian cortex, neurons and glia form a patterned structure across six
      layers whose complex cytoarchitectonic arrangement is likely to contribute to
      cognition. We sequenced transcriptomes from layers 1-6b of different areas
      (primary and secondary) of the adult (postnatal day 56) mouse somatosensory
      cortex to understand the transcriptional levels and functional repertoires of
      coding and noncoding loci for cells constituting these layers. A total of 5,835
      protein-coding genes and 66 noncoding RNA loci are differentially expressed
      ("patterned") across the layers, on the basis of a machine-learning model (naive
      Bayes) approach. Layers 2-6b are each associated with specific functional and
      disease annotations that provide insights into their biological roles. This new
      resource (http://genserv.anat.ox.ac.uk/layers) greatly extends currently
      available resources, such as the Allen Mouse Brain Atlas and microarray data
      sets, by providing quantitative expression levels, by being genome-wide, by
      including novel loci, and by identifying candidate alternatively spliced
      transcripts that are differentially expressed across layers.

PMID- 21867879
TI  - New rabies virus variants for monitoring and manipulating activity and gene
      expression in defined neural circuits.
AB  - Glycoprotein-deleted (DeltaG) rabies virus is a powerful tool for studies of
      neural circuit structure. Here, we describe the development and demonstrate the
      utility of new resources that allow experiments directly investigating
      relationships between the structure and function of neural circuits. New methods
      and reagents allowed efficient production of 12 novel DeltaG rabies variants from
      plasmid DNA. These new rabies viruses express useful neuroscience tools,
      including the Ca(2+) indicator GCaMP3 for monitoring activity; Channelrhodopsin-2
      for photoactivation; allatostatin receptor for inactivation by ligand
      application; and rtTA, ER(T2)CreER(T2), or FLPo, for control of gene expression.
      These new tools allow neurons targeted on the basis of their connectivity to have
      their function assayed or their activity or gene expression manipulated.
      Combining these tools with in vivo imaging and optogenetic methods and/or
      inducible gene expression in transgenic mice will facilitate experiments
      investigating neural circuit development, plasticity, and function that have not
      been possible with existing reagents.

PMID- 21867880
TI  - Cadherin-6 mediates axon-target matching in a non-image-forming visual circuit.
AB  - Neural circuits consist of highly precise connections among specific types of
      neurons that serve a common functional goal. How neurons distinguish among
      different synaptic targets to form functionally precise circuits remains largely
      unknown. Here, we show that during development, the adhesion molecule cadherin-6
      (Cdh6) is expressed by a subset of retinal ganglion cells (RGCs) and also by
      their targets in the brain. All of the Cdh6-expressing retinorecipient nuclei
      mediate non-image-forming visual functions. A screen of mice expressing GFP in
      specific subsets of RGCs revealed that Cdh3-RGCs which also express Cdh6
      selectively innervate Cdh6-expressing retinorecipient targets. Moreover, in Cdh6
      deficient mice, the axons of Cdh3-RGCs fail to properly innervate their targets
      and instead project to other visual nuclei. These findings provide functional
      evidence that classical cadherins promote mammalian CNS circuit development by
      ensuring that axons of specific cell types connect to their appropriate synaptic
      targets.

PMID- 21867881
TI  - Cadherin-9 regulates synapse-specific differentiation in the developing
      hippocampus.
AB  - Our understanding of mechanisms that regulate the differentiation of specific
      classes of synapses is limited. Here, we investigate the formation of synapses
      between hippocampal dentate gyrus (DG) neurons and their target CA3 neurons and
      find that DG neurons preferentially form synapses with CA3 rather than DG or CA1
      neurons in culture, suggesting that specific interactions between DG and CA3
      neurons drive synapse formation. Cadherin-9 is expressed selectively in DG and
      CA3 neurons, and downregulation of cadherin-9 in CA3 neurons leads to a selective
      decrease in the number and size of DG synapses onto CA3 neurons. In addition,
      loss of cadherin-9 from DG or CA3 neurons in vivo leads to striking defects in
      the formation and differentiation of the DG-CA3 mossy fiber synapse. These
      observations indicate that cadherin-9 bidirectionally regulates DG-CA3 synapse
      development and highlight the critical role of differentially expressed molecular
      cues in establishing specific connections in the mammalian brain.

PMID- 21867883
TI  - First node of Ranvier facilitates high-frequency burst encoding.
AB  - In central neurons the first node of Ranvier is located at the first axonal
      branchpoint, ~ 100 MUm from the axon initial segment where synaptic inputs are
      integrated and converted into action potentials (APs). Whether the first node
      contributes to this signal transformation is not well understood. Here it was
      found that in neocortical layer 5 axons, the first branchpoint is required for
      intrinsic high-frequency (>= 100 Hz) AP bursts. Furthermore, block of nodal Na(+)
      channels or axotomy of the first node in intrinsically bursting neurons
      depolarized the somatic AP voltage threshold (~ 5 mV) and eliminated APs
      selectively within a high-frequency cluster in response to steady currents or
      simulated synaptic inputs. These results indicate that nodal persistent Na(+)
      current exerts an anterograde influence on AP initiation in the axon initial
      segment, revealing a computational role of the first node of Ranvier beyond
      conduction of the propagating AP.

PMID- 21867882
TI  - A role for repressive histone methylation in cocaine-induced vulnerability to
      stress.
AB  - Substance abuse increases an individual's vulnerability to stress-related
      illnesses, which is presumably mediated by drug-induced neural adaptations that
      alter subsequent responses to stress. Here, we identify repressive histone
      methylation in nucleus accumbens (NAc), an important brain reward region, as a
      key mechanism linking cocaine exposure to increased stress vulnerability.
      Repeated cocaine administration prior to subchronic social defeat stress
      potentiated depressive-like behaviors in mice through decreased levels of histone
      H3 lysine 9 dimethylation in NAc. Cre-mediated reduction of the histone
      methyltransferase, G9a, in NAc promoted increased susceptibility to social
      stress, similar to that observed with repeated cocaine. Conversely, G9a
      overexpression in NAc after repeated cocaine protected mice from the consequences
      of subsequent stress. This resilience was mediated, in part, through repression
      of BDNF-TrkB-CREB signaling, which was induced after repeated cocaine or stress.
      Identifying such common regulatory mechanisms may aid in the development of new
      therapies for addiction and depression.

PMID- 21867884
TI  - Parallel mechanisms encode direction in the retina.
AB  - In the retina, presynaptic inhibitory mechanisms that shape directionally
      selective (DS) responses in output ganglion cells are well established. However,
      the nature of inhibition-independent forms of directional selectivity remains
      poorly defined. Here, we describe a genetically specified set of ON-OFF DS
      ganglion cells (DSGCs) that code anterior motion. This entire population of DSGCs
      exhibits asymmetric dendritic arborizations that orientate toward the preferred
      direction. We demonstrate that morphological asymmetries along with nonlinear
      dendritic conductances generate a centrifugal (soma-to-dendrite) preference that
      does not critically depend upon, but works in parallel with the GABAergic
      circuitry. We also show that in symmetrical DSGCs, such dendritic DS mechanisms
      are aligned with, or are in opposition to, the inhibitory DS circuitry in
      distinct dendritic subfields where they differentially interact to promote or
      weaken directional preferences. Thus, pre- and postsynaptic DS mechanisms
      interact uniquely in distinct ganglion cell populations, enabling efficient DS
      coding under diverse conditions.

PMID- 21867885
TI  - Pioneer GABA cells comprise a subpopulation of hub neurons in the developing
      hippocampus.
AB  - Connectivity in the developing hippocampus displays a functional organization
      particularly effective in supporting network synchronization, as it includes
      superconnected hub neurons. We have previously shown that hub network function is
      supported by a subpopulation of GABA neurons. However, it is unclear whether hub
      cells are only transiently present or later develop into distinctive subclasses
      of interneurons. These questions are difficult to assess given the heterogeneity
      of the GABA neurons and the poor early expression of markers. To circumvent this
      conundrum, we used "genetic fate mapping" that allows for the selective labeling
      of GABA neurons based on their place and time of origin. We show that early
      generated GABA cells form a subpopulation of hub neurons, characterized by an
      exceptionally widespread axonal arborization and the ability to single-handedly
      impact network dynamics when stimulated. Pioneer hub neurons remain into
      adulthood, when they acquire the classical markers of long-range projecting GABA
      neurons.

PMID- 21867886
TI  - A synaptic strategy for consolidation of convergent visuotopic maps.
AB  - The mechanisms by which experience guides refinement of converging afferent
      pathways are poorly understood. We describe a vision-driven refinement of
      corticocollicular inputs that determines the consolidation of retinal and visual
      cortical (VC) synapses on individual neurons in the superficial superior
      colliculus (sSC). Highly refined corticocollicular terminals form 1-2 days after
      eye-opening (EO), accompanied by VC-dependent filopodia sprouting on proximal
      dendrites, and PSD-95 and VC-dependent quadrupling of functional synapses.
      Delayed EO eliminates synapses, corticocollicular terminals, and spines on VC
      recipient dendrites. Awake recordings after EO show that VC and retina cooperate
      to activate sSC neurons, and VC light responses precede sSC responses within
      intervals promoting potentiation. Eyelid closure is associated with more
      protracted cortical visual responses, causing the majority of VC spikes to follow
      those of the colliculus. These data implicate spike-timing plasticity as a
      mechanism for cortical input survival, and support a cooperative strategy for
      retinal and cortical coinnervation of the sSC.

PMID- 21867887
TI  - Perceptual classification in a rapidly changing environment.
AB  - Humans and monkeys can learn to classify perceptual information in a
      statistically optimal fashion if the functional groupings remain stable over many
      hundreds of trials, but little is known about categorization when the environment
      changes rapidly. Here, we used a combination of computational modeling and
      functional neuroimaging to understand how humans classify visual stimuli drawn
      from categories whose mean and variance jumped unpredictably. Models based on
      optimal learning (Bayesian model) and a cognitive strategy (working memory model)
      both explained unique variance in choice, reaction time, and brain activity.
      However, the working memory model was the best predictor of performance in
      volatile environments, whereas statistically optimal performance emerged in
      periods of relative stability. Bayesian and working memory models predicted
      decision-related activity in distinct regions of the prefrontal cortex and
      midbrain. These findings suggest that perceptual category judgments, like value
      guided choices, may be guided by multiple controllers.

PMID- 21867888
TI  - Hippocampal "time cells" bridge the gap in memory for discontiguous events.
AB  - The hippocampus is critical to remembering the flow of events in distinct
      experiences and, in doing so, bridges temporal gaps between discontiguous events.
      Here, we report a robust hippocampal representation of sequence memories,
      highlighted by "time cells" that encode successive moments during an empty
      temporal gap between the key events, while also encoding location and ongoing
      behavior. Furthermore, just as most place cells "remap" when a salient spatial
      cue is altered, most time cells form qualitatively different representations
      ("retime") when the main temporal parameter is altered. Hippocampal neurons also
      differentially encode the key events and disambiguate different event sequences
      to compose unique, temporally organized representations of specific experiences.
      These findings suggest that hippocampal neural ensembles segment temporally
      organized memories much the same as they represent locations of important events
      in spatially defined environments.

PMID- 21867890
TI  - Carbonic maceration wines: characteristics and winemaking process.
AB  - Invented by Michel Flanzy in 1934, carbonic maceration involves placing the
      intact grape clusters into a closed tank with a carbon dioxide-rich atmosphere.
      The berries subsequently undergo an intracellular fermentation without yeast
      intervention. Complex changes occur during this process which entail the
      transformation of a small amount of sugar into alcohol (1.5-2% alcohol), the
      reduction of malic acid content by about half, and the generation of secondary
      products. Compared with wines produced by conventional techniques, carbonic
      maceration produces wines of distinctive character of superior quality possessing
      a harmonious balance. It can be used to generate a wide range of wines (red as
      well as rose), to be drunk young or aged. The process is composed of four steps:
      vatting of intact berries, "maceration-fermentation," pumping off, and pressing,
      followed by a second fermentation phase. Exchanges and interactions occur between
      grape berries, the gaseous atmosphere, and the must present at the bottom of the
      tank during the first step of the carbonic maceration winemaking process. Yeast
      fermentation starts at this stage, in the liquid phase, and continues throughout
      the second step as well, with the malolactic fermentation. The specific
      conditions required for a good handling of carbonic maceration are presented.

PMID- 21867889
TI  - Perceptual learning reduces interneuronal correlations in macaque visual cortex.
AB  - Responses of neurons in early visual cortex change little with training and
      appear insufficient to account for perceptual learning. Behavioral performance,
      however, relies on population activity, and the accuracy of a population code is
      constrained by correlated noise among neurons. We tested whether training changes
      interneuronal correlations in the dorsal medial superior temporal area, which is
      involved in multisensory heading perception. Pairs of single units were recorded
      simultaneously in two groups of subjects: animals trained extensively in a
      heading discrimination task, and "naive" animals that performed a passive
      fixation task. Correlated noise was significantly weaker in trained versus naive
      animals, which might be expected to improve coding efficiency. However, we show
      that the observed uniform reduction in noise correlations leads to little change
      in population coding efficiency when all neurons are decoded. Thus, global
      changes in correlated noise among sensory neurons may be insufficient to account
      for perceptual learning.

PMID- 21867891
TI  - Sherry wines.
AB  - Sherry wines are among the most distinctive Spanish wines, mainly produced in the
      southern Spain (particularly in Jerez and Montilla-Moriles), using traditional
      practices aimed at ensuring uniform quality and characteristics over time.
      Several types of Sherry wines are produced depending on the winemaking
      conditions. Fino-type wines are characterized by a dynamic biological aging, in
      which a layer of yeast grows in the surface of the wine (flor velum). On the
      contrary, Oloroso-type sherry wines are subjected to an oxidative aging, while
      Amontillado-type Sherries are produced by combining both production systems.
      Therefore, these wines undergo different biological and chemical processes that
      affect distinctively their chemical composition and their aroma and sensory
      characteristics. Through this review, the main aspects involved in the winemaking
      technology of sherry wines, and the latest scientific findings related to the
      microbiota of the flor film and other aspects associated to the changes in their
      chemical and sensory composition during aging will be revised. Some new trends in
      sherry wine technology focused on the acceleration of the biological aging or the
      use of organic grapes will be also considered.

PMID- 21867892
TI  - Vin Santo.
AB  - Vin Santo is the typical dessert wine produced in Tuscany, in particular, and in
      other areas of central and northern Italy, as well as on the Greek island of
      Santorini. It remains one of the most important "meditation wines", whose glamour
      starts with its ancient and mysterious origin. Italy is the country with the
      World's greatest tradition for sweet wine production. In this contest most of the
      steps in the Vin Santo making process are still linked to old local traditions.
      This chapter provides an overview of the different styles of Vin Santo produced
      in Italy together with its marketing. The main factors affecting grapes drying,
      alcoholic fermentation, maturation in barrels, are also described. So far there
      have been few scientific studies that have focused on Vin Santo. However, the
      increasing demand registered in the last few years for this kind of wine, is now
      greatly stimulating the research aimed to better manage its peculiar production
      process.

PMID- 21867893
TI  - Mead production: tradition versus modernity.
AB  - Honey is a natural product with recognized physical and chemical properties,
      which contribute to its biological activity. However, honey is currently being
      sold at low prices, making it imperative to find alternatives to make apiculture
      a viable national enterprise. One of these alternatives could be mead production.
      Despite the excellent properties of honey, mead production faces several
      problems, namely, delays and "pouts" fermentations, lack of product uniformity,
      and production of yeast off-flavors. Many factors might be related with these
      problems, such as honey variety, temperature, medium composition (vitamin and
      nitrogen content), fermentative yeast, and pH. Due to all these factors, mead
      production has decreased over the years. To overcome this situation, more
      research is needed to optimize the production of this beverage. This chapter
      presents a comprehensive review of previous research on mead production. It will
      focus on honey characterization and mead production. The first section covers
      honey composition and the way this affects honey properties, as well as important
      parameters that are indicators of honey quality. The second section discusses
      mead production, including fermentative microorganisms, fermentation conditions,
      and required postfermentation adjustments and maturation conditions. The final
      section focuses on the problems that must be surpassed and what the future holds
      for mead production.

PMID- 21867894
TI  - Port wine.
AB  - Port wine is a fortified wine with its origin in the Douro Demarcated Region but
      also includes Oporto city and the Entreposto of Gaia. Soil, climate, and
      viticultural conditions are important parameters used to classify and select the
      best vineyards to produce port wine. Taking into account the winemaking process,
      two major groups of wines can be distinguished: The wood ports and the bottle
      aged ports. These distinct conditions and processes ensure that there is not an
      unique port wine but, several ports, whose colors range from white to deep purple
      and that present a wide variety of flavors: vintage, late-bottled vintage,
      crusted, indication of age, colheita, reserve, white, tawny, ruby, and rose.

PMID- 21867895
TI  - Botrytized wines.
AB  - Botrytized wines are natural sweet wines, produced from grapes that are affected
      by Botrytis cinerea under particular conditions. This rare and special form of
      fungal infection, called noble rot, includes complex enzymatic conversions and
      concurrent dehydration of the grape berry and results in a highly concentrated
      final product. The main characteristics of the noble rotted grapes involve high
      sugar, acid, glycerol and mineral contents, special polysaccharides, and
      particular aroma composition, which are thoroughly studied. The saprophytic
      microbiota of the grapes is also affected. Harvest and vinification of the noble
      rotted grapes are difficult, having special requirements. Microbiology and
      biochemistry of the alcoholic fermentation in these wines have been recently
      studied more deeply. Depending on the grape varieties as well as vinification and
      ageing technologies, botrytized wines show large diversity in style. Most of them
      are rich in polyphenols, possessing high antioxidant capacity. Biogenic amine and
      micotoxine contents of these wines are no public health concerns. This chapter
      presents the microbiological, biochemical, and technological aspects of noble rot
      and botrytized wines and discusses the recent findings on these fields.

PMID- 21867896
TI  - Distinctive characteristics of Madeira wine regarding its traditional winemaking
      and modern analytical methodologies.
AB  - Madeira wine, a fortified wine produced in Madeira Island, is a special wine
      among all types of wine due its specific winemaking process. The aim of this
      chapter is to describe important aspects of Madeira winemaking and some
      scientific research currently carried out in these particular kinds of wines. The
      first part of the chapter concerns the most important aspects of winemaking
      technology used in Madeira wine production. The second part, the more extensive,
      deals with the different groups of compounds and how these are modified during
      the various steps of the production process, namely the aging period.

PMID- 21867897
TI  - Vermouth: technology of production and quality characteristics.
AB  - The aperitif wine, known as vermouth, is primarily prepared by adding a mixture
      of herbs and spices or their extract to a base wine. As such, it could also be
      called aromatized liquor, or a fortified wine. Various plant parts, such as
      seeds, wood, leaves, bark, or roots in dry form can be used in flavoring. These
      additives may be infused, macerated, or distilled in a base white wine, or added
      at various stages of preparation. The final liquid is filtered, pasteurized, and
      fortified (by the addition of alcohol). Some vermouths are sweetened, whereas
      other are left unsweetened (dry vermouth). These tend to have a bitterish finish.
      The two versions differ in alcohol content as well. Vermouths are most commonly
      prepared from grape-based wines, but fruit-based wines made from mango, apple,
      plum, sand pear, and wild apricot may also be used. These possess distinct
      physicochemical and sensory qualities from standard vermouths. The review gives
      comprehensive information on the historical developments and technology of
      vermouth production, the various spices and herbs used in its production, and its
      quality characteristics. In addition, the chapter also discusses the commercial
      potential of nongrape fruits in vermouth production.

PMID- 21867898
TI  - Amarone: a modern wine coming from an ancient production technology.
AB  - Amarone wine is a renowned dry red wine produced in Valpolicella (Verona,
      Northern Italy). It is made from local grapes varieties (Corvina, Rondinella, and
      Molinara) that are slowly dried under natural conditions during the fall into
      winter. After the postharvest drying, carried out for several weeks in dedicated
      lofts called fruttaio, the grapes are vinified: crushed, given prefermentative
      cold maceration, undergo alcoholic fermentation on the skins, malolactic
      fermentation, and finally maturation. The partially dried grapes are
      traditionally crushed during the second half of January to February. Because
      cellar conditions are unfavorable for either alcohol or malolactic fermentation,
      selected microbial cultures (yeasts and malolactic bacteria) are often necessary
      to correctly manage fermentation. The progress of both fermentation processes
      needs constant surveillance. During maturation conducted in vessels or wooden
      containers (tonneau in durmast oak), clarification and stabilization lead to
      improvements in quality. Product specifications require that Amarone not be
      bottled before the wine has been aged for 2years (Anonymous (2010). Disciplinare
      di produzione dei vini a denominazione di Origine Controllata e Garantita
      "Amarone della Valpolicella". Gazzetta Ufficiale della Repubblica Italiana. Serie
      generale n. 84. April 12). Amarone achieved its DOCG (Controlled and Guaranteed
      Denomination) status in 2010.

PMID- 21867899
TI  - 30 years is a long time.

PMID- 21867900
TI  - The crisis of IRIS: what every nurse should know about immune reconstitution
      inflammatory syndrome in patients infected with HIV.
AB  - Most health care providers are aware that beginning combination antiretroviral
      therapy (ART) for patients infected with HIV has reduced morbidity of AIDS
      related opportunistic infections and subsequently reduced HIV-related mortality.
      Effective ART leads to significantly reduced viral loads and increased CD4+ T
      cell counts, especially in the first few months after initiation. ART stimulates
      immune system reconstitution, thereby reducing the risk of exacerbation or
      acquisition of an opportunistic infection.

PMID- 21867901
TI  - From the editor's perspective....

PMID- 21867902
TI  - Peripheral arterial disease and disability from NHANES 2001-2004 data.
AB  - Peripheral arterial disease (PAD) can lead to long-term disability, but diagnosis
      frequently occurs late in the process. The purpose was to study the relationship
      between severity of PAD and disability (health-related quality of life), using a
      national sample (NHANES 2001-2004). A cross-sectional design examined 4559 adults
      age 40 and over. An ankle-brachial index (ABI) measured PAD severity and the
      Center for Disease Control and Prevention Health-Related Quality of Life 4
      question set measured physical, mental and activity disability. Sociodemographic
      level, chronic disease diagnosis, biological risk factors, pain, mobility and
      activity alterations in response to PAD were explored. Moderately-severe (ABI
      less than 0.7), mild (ABI 0.7 - 0.9) and no disease (0.91 - 1.5) showed that
      differences in pain, activity, mobility and risk factors become apparent when PAD
      is considered asymptomatic. Logistic regression showed physical disability was
      1.7 times (95% CI 1.3, 2.2) more likely with mild PAD than with no disease.
      Education, poverty income ratio and hypertension were confounding factors.
      Mobility difficulty and calf pain with walking were mediators between PAD and
      physical disability. Age, ability to do vigorous activity, total cholesterol and
      obesity were effect moderators. Mobility, vigorous activity and calf pain made
      the most difference in the relationship between PAD and physical disability.

PMID- 21867903
TI  - Comparison of three types of diabetic foot ulcer education plans to determine
      patient recall of education.
AB  - Type 2 diabetes affects almost 4% of the world's population and the rates of
      amputation range from 43.9 per 100,000 per year among Americans. As healthcare
      providers, we can motivate our patients and improve compliance if we better
      understand the learning styles of our patients. The need to better prepare
      patients and caregivers to manage illnesses and participate as partners in their
      care has been recognized as a national priority. This study of educational
      preferences for diabetic patients with a risk for developing foot ulcers utilizes
      a written education plan provided by the hospital and a video developed by the
      staff of the vascular surgery inpatient unit. One hundred participants were
      initially requested; however, the final sample of 30 individuals completed the
      study from the beginning of hospitalization to day of discharge. The majority of
      patients were able to increase their post-education test scores using the video
      education tool. A significant difference between the pretest and posttest scores
      for the groups who received video education was found. In contrast, although
      there was an improvement in pretest and posttest scores for the written-material
      only group and the written/video material group, this difference was not
      statistically significant. Diabetes in adults is increasing in our community;
      however, the sample size was not representative of the population. A follow-up
      study is needed to provide more evidence of patient preferences when education
      about their illness is presented in any format.

PMID- 21867904
TI  - The at-risk foot: what to do before and after amputation.
AB  - The best predicator of amputation is a history of previous amputation. A history
      of lower extremity ulceration or amputation increases the risk for further
      ulceration, infection, and subsequent amputation. Early diagnosis, control of
      risk factors, medical management, and timely revascularization may aid in
      avoiding limb loss. Treatment combines patient education, orthoses, footwear, and
      off-loading. Patients at risk should understand the implications of loss of
      protective sensation, the importance of carefully monitoring their feet, proper
      care of the foot, and always wearing protective footwear. It is important to
      control risk factors, protect the limb, recognize early signs of inflammation,
      and optimize wound care. Lower extremity amputation is a common outcome for
      patients with an at-risk foot. Amputation may be the best option to optimize
      function.

PMID- 21867905
TI  - Review of an article: Gardner AW, Parker DE, Montgomery PS, Scott KJ, Blevins SM.
      Efficacy of quantified home-based exercise and supervised exercise in patients
      with intermittent claudication: a randomized controlled trial. Circulation
      2011;123(5):491-98.

PMID- 21867906
TI  - Taking stock of telomere length at telome health.

PMID- 21867907
TI  - Antibiotic discovery: a step in the right direction.

PMID- 21867908
TI  - A new fluorescence-based assay for autophagy.

PMID- 21867909
TI  - A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin
      mediated oxidative stress responses in vivo.
AB  - Hydrogen peroxide (H(2)O(2)) can serve as a beneficial signaling agent or toxin
      depending on its concentration and location within a cell or organism. Methods to
      measure the localized accumulation of H(2)O(2) in living specimens remain
      limited. Motivated to meet this need, we have developed a nuclear-localized
      fluorescent probe for H(2)O(2), Nuclear Peroxy Emerald 1 (NucPE1), to selectively
      interrogate ROS fluxes within this sensitive organelle. NucPE1 selectively
      accumulates in the nuclei of a variety of mammalian cell lines as well as in
      whole model organisms like Caenorhabditis elegans, where it can respond to
      subcellular changes in H(2)O(2) fluxes. Moreover, in vivo NucPE1 imaging reveals
      a reduction in nuclear H(2)O(2) levels in worms overexpressing sir-2.1 compared
      with wild-type congeners, supporting a link between this longevity-promoting
      sirtuin protein and enhanced regulation of nuclear ROS pools.

PMID- 21867910
TI  - 2'-Fluoro substituents can mimic native 2'-hydroxyls within structured RNA.
AB  - The ability of fluorine in a C-F bond to act as a hydrogen bond acceptor is
      controversial. To test such ability in complex RNA macromolecules, we have
      replaced native 2'-OH groups with 2'-F and 2'-H groups in two related systems,
      the Tetrahymena group I ribozyme and the DeltaC209 P4-P6 RNA domain. In three
      cases the introduced 2'-F mimics the native 2'-OH group, suggesting that the
      fluorine atom can accept a hydrogen bond. In each of these cases the native
      hydroxyl group interacts with a purine exocyclic amine. Our results give insight
      about the properties of organofluorine and suggest a possible general biochemical
      signature for tertiary interactions between 2'-hydroxyl groups and exocyclic
      amino groups within RNA.

PMID- 21867911
TI  - Discovery of kibdelomycin, a potent new class of bacterial type II topoisomerase
      inhibitor by chemical-genetic profiling in Staphylococcus aureus.
AB  - Bacterial resistance to known therapeutics has led to an urgent need for new
      chemical classes of antibacterial agents. To address this we have applied a
      Staphylococcus aureus fitness test strategy to natural products screening. Here
      we report the discovery of kibdelomycin, a novel class of antibiotics produced by
      a new member of the genus Kibdelosporangium. Kibdelomycin exhibits broad
      spectrum, gram-positive antibacterial activity and is a potent inhibitor of DNA
      synthesis. We demonstrate through chemical genetic fitness test profiling and
      biochemical enzyme assays that kibdelomycin is a structurally new class of
      bacterial type II topoisomerase inhibitor preferentially inhibiting the ATPase
      activity of DNA gyrase and topoisomerase IV. Kibdelomycin is thus the first truly
      novel bacterial type II topoisomerase inhibitor with potent antibacterial
      activity discovered from natural product sources in more than six decades.

PMID- 21867912
TI  - A general framework for inhibitor resistance in protein kinases.
AB  - Protein kinases control virtually every aspect of normal and pathological cell
      physiology and are considered ideal targets for drug discovery. Most kinase
      inhibitors target the ATP binding site and interact with residue of a hinge loop
      connecting the small and large lobes of the kinase scaffold. Resistance to kinase
      inhibitors emerges during clinical treatment or as a result of in vitro selection
      approaches. Mutations conferring resistance to ATP site inhibitors often affect
      residues that line the ATP binding site and therefore contribute to selective
      inhibitor binding. Here, we show that mutations at two specific positions in the
      hinge loop, distinct from the previously characterized "gatekeeper," have general
      adverse effects on inhibitor sensitivity in six distantly related kinases,
      usually without consequences on kinase activity. Our results uncover a unifying
      mechanism of inhibitor resistance of protein kinases that might have widespread
      significance for drug target validation and clinical practice.

PMID- 21867914
TI  - XPF-dependent DNA breaks and RNA polymerase II arrest induced by antitumor DNA
      interstrand crosslinking-mimetic alkaloids.
AB  - Trabectedin and Zalypsis are two potent anticancer tetrahydroisoquinoline
      alkaloids that can form a covalent bond with the amino group of a guanine in
      selected triplets of DNA duplexes and eventually give rise to double-strand
      breaks. Using well-defined in vitro and in vivo assays, we show that the
      resulting DNA adducts stimulate, in a concentration-dependent manner, cleavage by
      the XPF/ERCC1 nuclease on the strand opposite to that bonded by the drug. They
      also inhibit RNA synthesis by: (1) preventing binding of transcription factors
      like Sp1 to DNA, and (2) arresting elongating RNA polymerase II at the same
      nucleotide position regardless of the strand they are located on. Structural
      models provide a rationale for these findings and highlight the similarity
      between this type of DNA modification and an interstrand crosslink.

PMID- 21867913
TI  - Novel proresolving aspirin-triggered DHA pathway.
AB  - Endogenous mechanisms in the resolution of acute inflammation are of interest
      because excessive inflammation underlies many pathologic abnormalities. We report
      an aspirin-triggered DHA metabolome that biosynthesizes a potent product in
      inflammatory exudates and human leukocytes, namely aspirin-triggered
      Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. The complete stereochemistry of
      AT-(NPD1/PD1) proved to be 10R,17R-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z
      hexaenoic acid. The chirality of hydroxyl groups and geometry of the conjugated
      triene system essential for bioactivity were established by matching biological
      materials with stereochemically pure isomers prepared by organic synthesis. AT
      (NPD1/PD1) reduced neutrophil (PMN) recruitment in murine peritonitis in a dose
      dependent fashion whereby neither a Delta(15)-trans-isomer nor DHA was effective.
      With human cells, AT-(NPD1/PD1) decreased transendothelial PMN migration as well
      as enhanced efferocytosis of apoptotic human PMN by macrophages. These results
      indicate that AT-(NPD1/PD1) is a potent anti-inflammatory proresolving molecule.

PMID- 21867915
TI  - Preferential uptake of L- versus D-amino acid cell-penetrating peptides in a cell
      type-dependent manner.
AB  - The use of protease-resistant D-peptides is a prominent strategy for overcoming
      proteolytic sensitivity in the use of cell-penetrating peptides (CPPs) as
      delivery vectors. So far, no major differences have been reported for the uptake
      of L- and D-peptides. Here we report that cationic L-CPPs are taken up more
      efficiently than their D-counterparts in MC57 fibrosarcoma and HeLa cells but not
      in Jurkat T leukemia cells. Reduced uptake of D-peptides co-occurred with
      persistent binding to heparan sulfates (HS) at the plasma membrane. In vitro
      binding studies of L- and D-peptides with HS indicated similar binding
      affinities. Our results identify two key events in the uptake of CPPs: binding to
      HS chains and the initiation of internalization. Only the second event depends on
      the chirality of the CPP. This knowledge may be exploited for a stereochemistry
      dependent preferential targeting of cells.

PMID- 21867916
TI  - Functional plasticity and allosteric regulation of alpha-ketoglutarate
      decarboxylase in central mycobacterial metabolism.
AB  - The alpha-ketoglutarate dehydrogenase (KDH) complex is a major regulatory point
      of aerobic energy metabolism. Mycobacterium tuberculosis was reported to lack KDH
      activity, and the putative KDH E1o component, alpha-ketoglutarate decarboxylase
      (KGD), was instead assigned as a decarboxylase or carboligase. Here, we show that
      this protein does in fact sustain KDH activity, as well as the additional two
      reactions, and these multifunctional properties are shared by the Escherichia
      coli homolog, SucA. We also show that the mycobacterial enzyme is finely
      regulated by an additional acyltransferase-like domain and by the action of
      acetyl-CoA, a powerful allosteric activator able to enhance the concerted protein
      motions observed during catalysis. Our results uncover the functional plasticity
      of a crucial node in bacterial metabolism, which may be important for M.
      tuberculosis during host infection.

PMID- 21867917
TI  - Analysis of the ketosynthase-chain length factor heterodimer from the
      fredericamycin polyketide synthase.
AB  - The pentadecaketide fredericamycin has the longest carbon chain backbone among
      polycyclic aromatic polyketide antibiotics whose biosynthetic genes have been
      sequenced. This backbone is synthesized by the bimodular fdm polyketide synthase
      (PKS). Here, we demonstrate that the bimodular fdm PKS as well as its elongation
      module alone synthesize undecaketides and dodecaketides. Thus, unlike other
      homologs, the fdm ketosynthase-chain length factor (KS-CLF) heterodimer does not
      exclusively control the backbone length of its natural product. Using sequence-
      and structure-based approaches, 48 CLF multiple mutants were engineered and
      analyzed. Unexpectedly, the I134F mutant was unable to turn over but could
      initiate and partially elongate the polyketide chain. This unprecedented mutant
      suggests that the KS-CLF heterodimer harbors an as yet uncharacterized chain
      termination mechanism. Together, our findings reveal fundamental mechanistic
      differences between the fdm PKS and its well-studied homologs.

PMID- 21867919
TI  - A sensitive and quantitative technique for detecting autophagic events based on
      lysosomal delivery.
AB  - We sought to develop a sensitive and quantitative technique capable of monitoring
      the entire flux of autophagy involving fusion of lysosomal membranes. We observed
      the accumulation inside lysosomal compartments of Keima, a coral-derived acid
      stable fluorescent protein that emits different-colored signals at acidic and
      neutral pHs. The cumulative fluorescent readout can be used to quantify autophagy
      at a single time point. Remarkably, the technique led us to characterize an
      autophagy pathway in Atg5-deficient cells, in which conventional LC3-based
      autophagosome probes are ineffective. Due to the large Stokes shift of Keima,
      this autophagy probe can be visualized in conjunction with other green-emitting
      fluorophores. We examined mitophagy as a selective autophagic process; time-lapse
      imaging of mitochondria-targeted Keima and GFP-Parkin allowed us to observe
      simultaneously Parkin recruitment to and autophagic degradation of mitochondria
      after membrane depolarization.

PMID- 21867920
TI  - Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type
      cannabinoid CB(2) receptor inverse agonists.
AB  - The cannabinoid CB(2) receptor is known to modulate osteoclast function by poorly
      understood mechanisms. Here, we report that the natural biphenyl neolignan 4'-O
      methylhonokiol (MH) is a CB(2) receptor-selective antiosteoclastogenic lead
      structure (K(i) < 50 nM). Intriguingly, MH triggers a simultaneous G(i) inverse
      agonist response and a strong CB(2) receptor-dependent increase in intracellular
      calcium. The most active inverse agonists from a library of MH derivatives
      inhibited osteoclastogenesis in RANK ligand-stimulated RAW264.7 cells and primary
      human macrophages. Moreover, these ligands potently inhibited the
      osteoclastogenic action of endocannabinoids. Our data show that CB(2) receptor
      mediated cAMP formation, but not intracellular calcium, is crucially involved in
      the regulation of osteoclastogenesis, primarily by inhibiting macrophage
      chemotaxis and TNF-alpha expression. MH is an easily accessible CB(2) receptor
      selective scaffold that exhibits a novel type of functional heterogeneity.

PMID- 21867918
TI  - Targeting MgrA-mediated virulence regulation in Staphylococcus aureus.
AB  - Increasing antibiotic resistance in human pathogens necessitates the development
      of new approaches against infections. Targeting virulence regulation at the
      transcriptional level represents a promising strategy yet to be explored. A
      global transcriptional regulator, MgrA in Staphylococcus aureus, was identified
      previously as a key virulence determinant. We have performed a fluorescence
      anisotropy (FA)-based high-throughput screen that identified 5, 5
      methylenedisalicylic acid (MDSA), which blocks the DNA binding of MgrA. MDSA
      represses the expression of alpha-toxin that is up-regulated by MgrA and
      activates the transcription of protein A, a gene down-regulated by MgrA. MDSA
      alters bacterial antibiotic susceptibilities via an MgrA-dependent pathway. A
      mouse model of infection indicated that MDSA could attenuate S. aureus virulence.
      This work is a rare demonstration of utilizing small molecules to block protein
      DNA interaction, thus tuning important biological regulation at the
      transcriptional level.

PMID- 21867921
TI  - Taking the sting out of malaria.
AB  - The innate immune response to malaria is a major determinant of disease severity
      and outcome. In this issue of Immunity, Sharma et al. (2011) provide evidence of
      a unique DNA sensing pathway that may contribute to immunopathology in plasmodial
      infections.

PMID- 21867922
TI  - A new vampire saga: the molecular mechanism of T cell trogocytosis.
AB  - In the current issue of Immunity, Martinez-Martin et al. (2011) describe the
      central supramolecular activation cluster (cSMAC) as a site of clathrin
      independent T cell receptor (TCR) internalization and trogocytosis. Further, they
      identify small Rho GTPases TC21 and RhoG as key mediators of these processes.

PMID- 21867923
TI  - Intracellular pathogens and CD8(+) dendritic cells: dangerous liaisons.
AB  - CD8(+) dendritic cells comprise a distinct cell type whose function is unclear.
      In this issue of Immunity, Mashayekhi et al. (2011) show these cells are
      essential for protection against the parasite Toxoplasma, but Edelson et al.
      (2011) show they are hijacked by Listeria during initial spreading.

PMID- 21867924
TI  - Value added: neural progenitor cells suppress inflammation and autoimmunity.
AB  - Neural progenitor cells (NPCs) can repair damaged myelin in neurodegenerative
      diseases. In this issue of Immunity, Cao et al. (2011) report that NPCs also
      produce the cytokine LIF, which suppresses Th17 cell-driven inflammation and
      autoimmunity by upregulating the protein Socs3.

PMID- 21867925
TI  - When the going gets tough, memory T cells check out.
AB  - Memory CD8(+) T cells proliferate faster than naive cells to rapidly control an
      infectious challenge, but West et al. (2011) in this issue of Immunity report
      that this superiority is lost in the face of a high dose or chronic viral
      challenge.

PMID- 21867926
TI  - CD8(+) T cells: foot soldiers of the immune system.
AB  - Resting naive CD8(+) T cells have an astounding capacity to react to pathogens by
      massive expansion and differentiation into cytotoxic effector cells that migrate
      to all corners of the body to clear the infection. The initial interaction with
      antigen-presenting cells in the central lymphoid organs drives an orchestrated
      program of differentiation aimed at producing sufficient numbers of effectors to
      get the job done without resulting in clonal exhaustion. Interactions with
      antigen-presenting cells and other immune cells continue at the site of infection
      to regulate further on-site expansion and differentiation, all with the goal of
      protecting the host with minimal bystander tissue damage. Here we review recent
      advances in CD8(+) T cell recognition of antigen in lymphoid as well as in
      nonlymphoid tissues in the periphery, and how CD8(+) T cell expansion and
      differentiation are controlled in these contexts.

PMID- 21867927
TI  - CD8alpha(+) dendritic cells are an obligate cellular entry point for productive
      infection by Listeria monocytogenes.
AB  - CD8alpha(+) dendritic cells (DCs) prime cytotoxic T lymphocytes during viral
      infections and produce interleukin-12 in response to pathogens. Although the loss
      of CD8alpha(+) DCs in Batf3(-/-) mice increases their susceptibility to several
      pathogens, we observed that Batf3(-/-) mice exhibited enhanced resistance to the
      intracellular bacterium Listeria monocytogenes. In wild-type mice, Listeria
      organisms, initially located in the splenic marginal zone, migrated to the
      periarteriolar lymphoid sheath (PALS) where they grew exponentially and induced
      widespread lymphocyte apoptosis. In Batf3(-/-) mice, however, Listeria organisms
      remain trapped in the marginal zone, failed to traffic into the PALS, and were
      rapidly cleared by phagocytes. In addition, Batf3(-/-) mice, which lacked the
      normal population of hepatic CD103(+) peripheral DCs, also showed protection from
      liver infection. These results suggest that Batf3-dependent CD8alpha(+) and
      CD103(+) DCs provide initial cellular entry points within the reticuloendothelial
      system by which Listeria establishes productive infection.

PMID- 21867928
TI  - CD8alpha(+) dendritic cells are the critical source of interleukin-12 that
      controls acute infection by Toxoplasma gondii tachyzoites.
AB  - CD8alpha(+) dendritic cells (DCs) are important in vivo for cross-presentation of
      antigens derived from intracellular pathogens and tumors. Additionally, secretion
      of interleukin-12 (IL-12) by CD8alpha(+) DCs suggests a role for these cells in
      response to Toxoplasma gondii antigens, although it remains unclear whether these
      cells are required for protection against T. gondii infection. Toward this goal,
      we examined T. gondii infection of Batf3(-/-) mice, which selectively lack only
      lymphoid-resident CD8alpha(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-)
      mice were extremely susceptible to T. gondii infection, with decreased production
      of IL-12 and interferon-gamma. IL-12 administration restored resistance in Batf3(
      /-) mice, and mice in which IL-12 production was ablated only from CD8alpha(+)
      DCs failed to control infection. These results reveal that the function of
      CD8alpha(+) DCs extends beyond a role in cross-presentation and includes a
      critical role for activation of innate immunity through IL-12 production during
      T. gondii infection.

PMID- 21867930
TI  - Preface.

PMID- 21867929
TI  - Genome-wide analyses of transcription factor GATA3-mediated gene regulation in
      distinct T cell types.
AB  - The transcription factor GATA3 plays an essential role during T cell development
      and T helper 2 (Th2) cell differentiation. To understand GATA3-mediated gene
      regulation, we identified genome-wide GATA3 binding sites in ten well-defined
      developmental and effector T lymphocyte lineages. In the thymus, GATA3 directly
      regulated many critical factors, including Th-POK, Notch1, and T cell receptor
      subunits. In the periphery, GATA3 induced a large number of Th2 cell-specific as
      well as Th2 cell-nonspecific genes, including several transcription factors. Our
      data also indicate that GATA3 regulates both active and repressive histone
      modifications of many target genes at their regulatory elements near GATA3
      binding sites. Overall, although GATA3 binding exhibited both shared and cell
      specific patterns among various T cell lineages, many genes were either
      positively or negatively regulated by GATA3 in a cell type-specific manner,
      suggesting that GATA3-mediated gene regulation depends strongly on cofactors
      existing in different T cells.

PMID- 21867931
TI  - 1990-2010: two decades of interferon-based therapy.
AB  - Twenty-five years have passed since interferon-alpha was first used in the
      treatment of chronic hepatitis C infection, and even now it remains an essential
      part of the standard of care for this condition. At present, the recommended
      treatment is a combination of pegylated interferon and ribavirin A. There have
      been enormous advances in our understanding of the mechanisms through which
      interferon works and in identifying factors related to the response to this
      treatment. Even with the development of new protease inhibitors, it is likely
      that interferon will remain an essential component of hepatitis C treatment.

PMID- 21867932
TI  - Naives, nonresponders, relapsers: who is there left to treat?
AB  - Hepatitis C has a high prevalence in the United States, and the disease burden of
      HCV will increase over the next 20 to 30 years by many estimates. Trials to
      evaluate new therapies and optimize the use of triple drug therapies are needed
      if HCV is to be successfully controlled and its incumbent morbidity and mortality
      drastically lowered for all groups of patients. With improvements in ability to
      achieve SVR with agents such as telaprevir and boceprevir, efforts to improve
      treatment uptake rates and to re-examine the utility of universal or more
      inclusive screening for chronic hepatitis C are warranted.

PMID- 21867933
TI  - Redefining baseline demographics: the role of genetic testing in hepatitis C
      virus infection.
AB  - The current standard of care for hepatitis C virus (HCV) infection is pegylated
      interferon and ribavirin. Unfortunately, treatment cures at best only 40% to 50%
      of patients infected with genotype 1 HCV, the most common HCV genotype in Western
      countries. Treatment is also expensive and is often poorly tolerated. Therefore,
      the identification of patients most likely to benefit from treatment is
      clinically important. Genome-wide association studies have recently identified
      genetic variants, most notably IL28B and ITPA, which will enhance the ability of
      clinicians to personalize antiviral therapy for HCV infection.

PMID- 21867934
TI  - An overview of emerging therapies for the treatment of chronic hepatitis C.
AB  - Chronic hepatitis C (CHC) is a leading cause of chronic hepatitis, cirrhosis,
      liver failure, and hepatocellular carcinoma (HCC) worldwide. Currently, pegylated
      interferon (Peg-IFN) and ribavirin therapy achieve curative responses in 40% to
      80% of patients, depending on genotype. Recognition of new therapeutic targets
      for HCV therapy has led to development of novel therapies. The purpose of this
      review is to summarize the status of novel therapeutics for CHC that promise to
      increase the safety and efficacy of therapy.

PMID- 21867935
TI  - Boceprevir: a user's guide.
AB  - Given its essential role in the process of hepatitis C virus (HCV) replication,
      the viral NS3/4A serine protease is arguably the most thoroughly characterized
      HCV enzyme and the most intensively pursued anti-HCV target for drug development
      thus far. Recent data have demonstrated promise for the NS3 protease inhibitor
      boceprevir, which, when added to the standard of care peginterferon and
      ribavirin, improves sustained virological response while shortening duration of
      therapy in genotype-1-infected individuals. This review discusses the mechanism
      of action of boceprevir, its effects on HCV, and its viral resistance.

PMID- 21867936
TI  - Telaprevir user's guide.
AB  - For a decade, standard therapy for patients with genotype 1 chronic HCV (HCV G1)
      consisted of pegylated interferon (Peg-IFN) alfa-2a or Peg-IFN alfa-2b, combined
      with ribavirin. Despite the improved efficacy of this therapy over others, the
      overall sustained virologic response rate in patients with HCV G1 was still low.
      This article discusses phase I, II, and III trials examining telaprevir's role in
      treating patients with HCV. We have now entered an era of combination therapy
      utilizing direct acting anti-virals, the start of which was marked by the FDA
      approval of HCV protease inhibitors.

PMID- 21867937
TI  - Management of the treatment-experienced patient infected with hepatitis C virus
      genotype 1: options and considerations.
AB  - Individuals infected with hepatitis C virus (HCV) are at risk for cirrhosis
      and/or hepatocellular carcinoma. Treatment of HCV infection has undergone several
      revisions over the past 15 years and continues to evolve. The current major
      advance is with the protease inhibitors in addition to pegylated interferon and
      ribavirin. The emergence of resistance needs to be monitored carefully as newer
      and more potent drugs are added to the interferon and ribavirin backbone drugs.
      In addition, adverse events will be more frequent and some novel ones will
      require special attention.

PMID- 21867938
TI  - The HIV/HCV-coinfected patient and new treatment options.
AB  - Hepatitis C (HCV) treatment is on the cusp of change with the approval of the
      first direct-acting antivirals: telaprevir and boceprevir. Drug-drug interactions
      with HIV antiretrovirals, increased toxicity, and rapid selection of HCV
      resistant mutants are among the treatment complexities expected in this difficult
      to-treat population. Until the current standard of care changes, focus should be
      on strategies to optimize management of HIV/HCV-coinfected patients with
      currently available options. This article reviews the latest predictive factors
      of response to HCV treatment with the current standard of care in HIV-coinfected
      patients, and new treatment options.

PMID- 21867939
TI  - Second-wave protease inhibitors: choosing an heir.
AB  - Infection with the hepatitis C virus (HCV) is a major cause of chronic liver
      disease and a leading indication of liver transplantations worldwide. The current
      standard of care for chronic hepatitis C is a combination of pegylated interferon
      alpha and ribavirin that is effective in slightly more than half of cases and is
      associated with significant side effects. The first directly acting antivirals
      recently reached the US market, but will have shortcomings that should in part be
      overcome by the second-wave PIs that are in development. This article gives an
      overview of the compounds that will soon be available.

PMID- 21867940
TI  - The HCV NS5B nucleoside and non-nucleoside inhibitors.
AB  - This article introduces one of the most diverse classes of direct-acting
      antivirals for hepatitis C, the nucleoside and non-nucleoside NS5B polymerase
      inhibitors. Through a systematic review of the published literature, we describe
      their structure, mechanism of action, issues with resistance, and clinical
      effectiveness shown in the latest clinical trials. Direct-acting antiviral
      combination trials that have already shown some early promising results even in
      the setting of interferon-sparing antiviral regimens are discussed.

PMID- 21867941
TI  - The NS5A replication complex inhibitors: difference makers?
AB  - The development and approval of direct-acting antiviral agents looks set to
      transform the treatment of chronic hepatitis C infection. Among the agents in
      development are novel compounds that inhibit the function of the NS5A protein: a
      pleiotropic protein with a complex and essential role in viral replication.
      Preclinical studies have demonstrated the potency of these agents across a broad
      range of viral genotypes, and in early phase trials, they rapidly suppressed
      viral replication when administered as monotherapy or in combination with
      pegylated interferon-alpha and ribavirin. The discovery and development of NS5A
      replication complex inhibitors is summarized in this review.

PMID- 21867942
TI  - Hepatitis C therapy: other players in the game.
AB  - Therapies in addition to the direct-acting antiviral agents (DAA) under
      evaluation for chronic hepatitis C include host targets such as cyclophilin
      inhibitors and immunomodulators. Both passive and therapeutic vaccines hold
      promise for the future. Although the numbers of drug categories and individual
      agents are increasing, only a handful of the non-DAAs seem to be ready to move on
      to phase III trials. New interferon agents are in development, and ribavirin
      variants are still under consideration. The role of the other players in the
      overall armamentarium against hepatitis C virus is still evolving.

PMID- 21867943
TI  - Mixing and matching drugs: what makes sense?
AB  - The introduction and ongoing development of directly acting antiviral agents
      (DAAs) and drugs targeting host cell structures will change the management of
      patients with chronic hepatitis C virus (HCV) infection. The concomitant use of
      the protease inhibitors telaprevir or boceprevir with the standard of care, a
      combination of pegylated interferon (PegIFN) and ribavirin, will represent the
      new standard for the treatment of HCV genotype 1 infection. Contraindications and
      side effects limit the applicability of interferon-based therapies and motivate
      the investigation of PegIFN-sparing regimens. Different DAA combinations under
      investigation are reviewed in this article.

PMID- 21867944
TI  - Interferon-free regimens: the near future, the likely and the not so likely.
AB  - Remarkable progress has been achieved in the treatment of chronic hepatitis C
      virus (HCV) since interferon was first used to treat this pathogen more than 20
      years ago. This article reviews the mechanisms through which interferon is
      believed to suppress HCV and lead to SVR. These observations are used to
      speculate as to whether an all-oral antiviral cocktail could "cure" HCV in the
      near future.

PMID- 21867945
TI  - Treatment as prevention for HIV.

PMID- 21867946
TI  - Influenza vaccination in young children.

PMID- 21867947
TI  - Influenza vaccination in young children.

PMID- 21867949
TI  - Influenza vaccination in young children.

PMID- 21867950
TI  - HIV status in serodiscordant couples.

PMID- 21867952
TI  - Treatment of drug-resistant tuberculosis.

PMID- 21867954
TI  - Treatment of drug-resistant tuberculosis.

PMID- 21867955
TI  - MDR tuberculosis and non-compliance with therapy.

PMID- 21867957
TI  - Streptococcus pneumoniae retroperitoneal and pelvic abscess.

PMID- 21867956
TI  - Antiscience and ethical concerns associated with advocacy of Lyme disease.
AB  - Advocacy for Lyme disease has become an increasingly important part of an
      antiscience movement that denies both the viral cause of AIDS and the benefits of
      vaccines and that supports unproven (sometimes dangerous) alternative medical
      treatments. Some activists portray Lyme disease, a geographically limited tick
      borne infection, as a disease that is insidious, ubiquitous, difficult to
      diagnose, and almost incurable; they also propose that the disease causes mainly
      non-specific symptoms that can be treated only with long-term antibiotics and
      other unorthodox and unvalidated treatments. Similar to other antiscience groups,
      these advocates have created a pseudoscientific and alternative selection of
      practitioners, research, and publications and have coordinated public protests,
      accused opponents of both corruption and conspiracy, and spurred legislative
      efforts to subvert evidence-based medicine and peer-reviewed science. The
      relations and actions of some activists, medical practitioners, and commercial
      bodies involved in Lyme disease advocacy pose a threat to public health.

PMID- 21867958
TI  - Re-evaluation of the function of the male specific lethal complex in Drosophila.
AB  - A set of proteins and noncoding RNAs, referred to as the male specific lethal
      (MSL) complex, is present on the male X chromosome in Drosophila and has been
      postulated to be responsible for dosage compensation of this chromosome - the up
      regulation of its expression to be equal to that of two X chromosomes in females.
      This hypothesis is evaluated in view of lesser known aspects of dosage
      compensation such as the fact that metafemales with three X chromosomes also have
      equal expression to normal females, which would require a down-regulation of each
      gene copy. Moreover, when this complex is ectopically expressed in females or
      specifically targeted to a reporter in males, there is no increase in expression
      of the genes or targets with which it is associated. These observations are not
      consistent with the hypothesis that the MSL complex conditions dosage
      compensation. A synthesis is described that can account for these observations.

PMID- 21867959
TI  - Characterization of a novel missense mutation on murine Pax3 through ENU
      mutagenesis.
AB  - N-ethyl-N-nitrosourea (ENU) mutagenesis has led to the elucidation of several
      regulator genes for melanocyte and skin development. Here we characterized a
      mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant,
      including exencephaly, spina bifida and abnormal limbs in homozygotes as well as
      white belly spotting and occasionally loop-tail in heterozygotes. This novel
      mutant was named as Sp(xG). Through genome-wide linkage analysis in backcross
      progenies with microsatellite markers, the Sp(xG) was confined to a region
      between D1MIT415 and D1MIT7 on chromosome 1, where notable Pax3 gene was located.
      Direct sequencing revealed that Sp(xG) carried a nucleotide A894G missense
      transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at
      amino acid 269 within the highly-conserved homeodomain (HD) DNA recognition
      module, which was the first point mutation found in this domain in mice. This
      N269D mutation impaired the transactivation capacity of Pax3 protein, but exerted
      no effect on Pax3 protein translation. The characterization of the new mutation
      expanded our understanding the transactivation and DNA-binding structure of Pax3
      protein.

PMID- 21867960
TI  - MDM2 SNP309 contributes to tumor susceptibility: a meta-analysis.
AB  - The potentially functional polymorphism, SNP309, in the promoter region of MDM2
      gene has been implicated in cancer risk, but individual published studies showed
      inconclusive results. To obtain a more precise estimate of the association
      between MDM2 SNP309 and risk of cancer, we performed a meta-analysis of 70
      individual studies in 59 publications that included 26,160 cases with different
      types of tumors and 33,046 controls. Summary odds ratios (OR) and corresponding
      95% confidence intervals (CIs) were estimated using fixed- and random-effects
      models when appropriate. Overall, the variant genotypes were associated with a
      significantly increased cancer risk for all cancer types in different genetic
      models (GG vs. TT: OR, 1.123; 95% CI, 1.056-1.193; GG/GT vs. TT: OR, 1.028; 95%
      CI, 1.006-1.050). In the stratified analyses, the increased risk remained for the
      studies of most types of cancers, Asian populations, and hospital- /population
      based studies in different genetic models, whereas significantly decreased risk
      was found in prostate cancer (GG vs. TT: OR, 0.606; 95% CI, 0.407-0.903; GG/GT
      vs. TT: OR, 0.748; 95% CI, 0.579-0.968). In conclusion, the data of meta-analysis
      suggests that MDM2 SNP309 is a potential biomarker for cancer risk.

PMID- 21867961
TI  - Allele-specific PCR genotyping of the HSP70 gene polymorphism discriminating the
      green and red color variants sea cucumber (Apostichopus japonicus).
AB  - Color variation is a well-known feature of sea cucumbers (Apostichopus
      japonicus), which are classified into three groups based on their colors of red,
      green and black. It is also one of the most important traits related to how they
      taste, and it thereby affects their market price. Attempts were made to identify
      single-nucleotide polymorphisms (SNPs) and to analyze differences associated with
      SNP genotypes between green and red color variants using HSP70 as the target
      gene. The HSP70 gene, which is found universally in organisms from bacteria to
      humans, is one of the most evolutionarily conserved genes and the most widely
      studied biomarker of stress response. DNA fragments of 1074 bp covering a partial
      sequence of the sea cucumber HSP70 gene, were amplified from both red and green
      variants, and subsequently analyzed for the presence of SNPs. Twenty-seven
      polymorphic sites in total, including heterozygous sites, were observed. Of
      these, six sites were found to be significantly different SNP genotypes between
      green and red variants. Furthermore, PCR with an internal primer designed to
      include an allele-specific SNP at the 3' end (site 443) showed differentiation
      between the two variants, 100% and 4.2% amplification in green and red variants,
      respectively. The validated SNPs may serve as informative genetic markers that
      can be used to distinguish variants at the early developmental stage, prior to
      color differentiation.

PMID- 21867962
TI  - Gene expression profiling of Puccinia striiformis f. sp. tritici during
      development reveals a highly dynamic transcriptome.
AB  - Puccinia striiformis f. sp. tritici (Pst) causes stripe rust, one of the most
      important diseases of wheat worldwide. cDNA libraries had been constructed from
      urediniospores, germinated urediniospores and haustoria. However, little is known
      about the expression patterns of the genes related to the infection process and
      sporulation of the pathogen. In this study, a custom oligonucleotide microarray
      was constructed using sequences of 442 gene transcripts selected from Pst cDNA
      libraries. The expression patterns of the genes were determined by hybridizing
      the microarray with cDNA from Pst in vitro and Pst-infected wheat leaves. The
      time course study identified 55 transcripts that were differentially expressed
      during the infection process in a compatible interaction. They were identified to
      have functions related to the following biological processes, including
      carbohydrate and lipid metabolism, energy, cell signaling, protein synthesis,
      cell structure and division. In an incompatible interaction, 17 transcripts of
      the pathogen were differentially expressed in resistant wheat leaves inoculated
      with an avirulent Pst race, ten of which had similar expression patterns to those
      in the compatible interaction. Several candidates for pathogenicity and
      virulence/avirulence related genes were also identified. The results of
      quantitative real-time PCR validated the expression patterns of some selected
      genes. The study demonstrates that the custom oligonucleotide microarray
      technology is useful to determine the expression patterns of the pathogen genes
      involved in different types of the host-pathogen interactions and stages of
      development.

PMID- 21867963
TI  - Discovery of quantitative trait loci for crossability from a synthetic wheat
      genotype.
AB  - Crossability between wheat and rye is an important trait for wheat improvement.
      No quantitative trait loci (QTLs) were detected from wheat ancestors previously.
      The objectives of this study were to dissect the QTLs for crossability using 111
      introgression lines (ILs) derived from synthetic hexaploid wheat. A total of 1275
      SSR markers were screened for polymorphism between the two parents, and 552
      markers of them displayed polymorphism, of which 64 were selected for genotyping
      the 111 BC(5)F(6) ILs. Field trials were performed in a Latinized alpha-lattice
      design in Luoyang and Jiaozuo of Henan Province of China in 2007-2008 and 2008
      2009 cropping seasons. One-way ANOVA and interval mapping (IM) analysis were used
      to detect QTL for crossability between wheat and rye. A total of 13 putative QTLs
      were detected. Five of them, QCa.caas.1A, QCa.caas.2D, QCa.caas.4B, QCa.caas.5B
      and QCa.caas.6A, were detected in both trials and three of them, QCa.caas.2D,
      QCa.caas.4B and QCa.caas.6A, were novel. The positive effect allele of the four
      QTLs came from the donor parent Am3 except QCa.caas.6A that came from the
      recurrent parent Laizhou953. ILs with both higher positive effect alleles and
      favorable agronomic traits developed in present study are elite germplasm for
      wide crossing in wheat. Results from the current study suggest that wheat
      ancestors can be rich in new sources of crossability genes.

PMID- 21867964
TI  - Species-specific functional evolution of neuroglobin.
AB  - Neuroglobin (Ngb) is a recently discovered vertebrate heme protein that is
      expressed in the brain and can reversibly bind oxygen. Human Ngb is involved in
      neuroprotection under oxidative stress conditions such as ischemia and
      reperfusion. We previously demonstrated that, on the one hand, human ferric Ngb
      binds to the alpha-subunit of heterotrimeric G proteins (Galpha(i)) and acts as a
      guanine nucleotide dissociation inhibitor (GDI) for Galpha(i). On the other hand,
      zebrafish Ngb does not exhibit GDI activity. By using wild-type and Ngb mutants,
      we demonstrated that the GDI activity of human Ngb is tightly correlated with its
      neuroprotective activity. The crucial residues for both GDI and neuroprotective
      activity, corresponding to Glu53, Arg97, Glu118, and Glu151 of human Ngb, are
      conserved among boreotheria of mammalia. Recently, we found that zebrafish, but
      not human, Ngb can translocate into cells and clarified that module M1 of
      zebrafish Ngb is important for protein transduction. By performing site-directed
      mutagenesis, we showed that Lys7, Lys9, Lys21, and Lys23 of zebrafish Ngb are
      crucial for protein transduction activity. Because these residues are conserved
      among fishes, but not among mammals, birds, reptilians, or amphibians, the
      ability to penetrate cell membranes may be a unique characteristic of fish Ngb
      proteins. Moreover, we clarified that zebrafish Ngb interacts with negatively
      charged cell-surface glycosaminoglycan. Taken together, these results suggest
      that the function of Ngb proteins has been changing dynamically throughout the
      evolution of life.

PMID- 21867965
TI  - Molecular cloning, mRNA expression, and characterization of heat shock protein 10
      gene from humphead snapper Lutjanus sanguineus.
AB  - Heat shock protein 10 (HSP10) gene of humphead snapper (Lutjanus sanguineus),
      designated as ByHSP10, was cloned by rapid amplification of cDNA ends (RACE)
      techniques with the primers designed from the known EST sequence identified from
      the subtracted cDNA library of the head kidney of humphead snapper. Sequence
      analysis showed the full length cDNA of ByHSP10 was 529bp, containing a 5'
      terminal untranslated region (UTR) of 51bp, a 3' terminal UTR of 181bp, and an
      open reading frame (ORF) of 297bp encoding a polypeptide of 99 amino acids. Based
      on the deduced amino acid sequence, the theoretical molecular mass of ByHSP10 was
      calculated to be 10.92kDa with an isoelectric point of 9.46. Moreover,
      chaperonins hsp10/cpn10 signature was found in the amino acids sequence of
      ByHSP10 by PredictProtein. BLAST analysis revealed that the amino acids of
      ByHSP10 had the highest homology of 88% compared with other HSP10s. Fluorescent
      real-time quantitative RT-PCR was used to examine the expression of ByHSP10 gene
      in eight kinds of tissues of humphead snapper after the challenge with Vibrio
      harveyi. There was a clear time-dependent expression pattern of ByHSP10 in head
      kidney, spleen and thymus after bacteria challenge. The expression of mRNA
      reached the maximum level at the time point of 9h, 6h and 24h, respectively and
      then returned to control level in 36h. The up-regulated mRNA expression of
      ByHSP10 in humphead snapper after bacteria challenge indicated that the HSP10
      gene was inducible and might be involved in immune response. A phylogenetic tree
      was constructed based on the ORF nucleotide sequences of HSP10 for 30 species.
      The relatonships among them were generally in agreement with the traditional
      taxonomy which suggested that HSP10 genes could aid in the system classification
      research.

PMID- 21867966
TI  - No chromosomal clustering of housekeeping genes in the marine chordate Ciona
      intestinalis.
AB  - Housekeeping genes, widely expressed genes that are required for the basal
      function of most cell types, are clustered in the human and worm genomes. This
      arrangement suggests coordinate control of housekeeping gene expression at the
      chromosomal level. Here we examined whether this notion is applicable to a marine
      chordate, Ciona intestinalis. Using microarrays, we analyzed genes that were
      expressed in 11 organs of the adult, including the neural complex, branchial sac,
      esophagus, stomach, endostyle, intestine, body-wall muscle, heart, blood cells,
      ovary and testis. This analysis identified 158 genes that are expressed
      ubiquitously in these organs. These housekeeping genes could be classified into a
      range of Gene Ontology categories, in particular, ribosomal protein components.
      Of these 158 genes, we were able to map 141 genes onto the 14 pairs of the C.
      intestinalis chromosomes. They were distributed rather evenly over all the
      chromosomes, except for small clusters containing two or three genes. Therefore,
      the notion of chromosomal clustering of housekeeping genes is not applicable in
      this chordate.

PMID- 21867967
TI  - Complete mitochondrial genome of Tubulipora flabellaris (Bryozoa: Stenolaemata):
      the first representative from the class Stenolaemata with unique gene order.
AB  - Mitochondrial genomes play a significant role in the reconstruction of
      phylogenetic relationships within metazoans. There are still many controversies
      concerning the phylogenetic position of the phylum Bryozoa. In this research, we
      have finished the complete mitochondrial genome of one bryozoan (Tubulipora
      flabellaris), which is the first representative from the class Stenolaemata. The
      complete mitochondrial genome of T. flabellaris is 13,763bp in length and
      contains 36 genes, which lacks the atp8 gene in contrast to the typical metazoan
      mitochondrial genomes. Gene arrangement comparisons indicate that the
      mitochondrial genome of T. flabellaris has unique gene order when compared with
      other metazoans. The four known bryozoans complete mitochondrial genomes also
      have very different gene arrangements, indicates that bryozoan mitochondrial
      genomes have experienced drastic rearrangements. To investigate the phylogenetic
      relationship of Bryozoa, phylogenetic analyses based on amino acid sequences of
      11 protein coding genes (excluding atp6 and atp8) from 26 metazoan complete
      mitochondrial genomes were made utilizing Maximum Likelihood (ML) and Bayesian
      methods, respectively. The results indicate the monopoly of Lophotrochozoa and a
      close relationship between Chaetognatha and Bryozoa. However, more evidences are
      needed to clarify the relationship between two groups. Lophophorate appeared to
      be polyphyletic according to our analyses. Meanwhile, neither analysis supports
      close relationship between Branchiopod and Phoronida. Four bryozoans form a clade
      and the relationship among them is T. flabellaris+(F. hispida+(B. neritina+W.
      subtorquata)), which is in coincidence with traditional classification system.

PMID- 21867968
TI  - Genome size, GC percentage and 5mC level in the Indonesian coelacanth Latimeria
      menadoensis.
AB  - The living fossil Latimeria menadoensis is important to understand sarcopterygian
      evolution. To gain further insights into this fish species we studied its genome
      size, GC% and 5mC level. The genome size and the GC% of the Indonesian coelacanth
      seem to be very similar to those of the African coelacanth. Moreover the GC%, the
      CpG frequency and the 5mC level of L. menadoensis are more similar to those of
      fish and amphibians than to those of mammals, birds and reptiles and this is in
      line with the hypothesis that two different DNA methylation and CpG shortage
      equilibria arose during vertebrate evolution. Our results suggest that the genome
      of L. menadoensis has remained unchanged for several million years, maybe since
      the origin of the lineage which from lobe-finned fish led to tetrapods. These
      data fit a conservative evolutionary landscape and suggest that the genome of the
      extant crossopterygians may be a sort of evolutionarily frozen genome.

PMID- 21867969
TI  - Annotation and analysis of expressed sequence tags (ESTs) from Chinese sturgeon
      (Acipenser sinensis) pituitary cDNA library.
AB  - Chinese sturgeon Acipenser sinensis belongs to the family Acipenseridae, an
      ancient species of actinopterygian fishes. In order to advance molecular research
      on its reproduction, ontogenetic development, we were seeking for genomic
      information in the NCBI expressed sequence tag (EST database). We found 3384
      indentified cDNA sequences which were assembled into 861 unigenes. Blast analysis
      revealed 301 unigenes shared high similarity with genes in the public databases,
      and these were classified into three groups: 202 known genes, 81 putative genes
      and 8 unknown genes. The remainder (560 genes) had no significant match to any
      protein sequence. Further, 255 unigenes and 333 unmatched unigenes were annotated
      with Gene Ontology (GO), which could be classified into cellular component,
      molecular function, and biological process. Among the known genes, the hormone
      genes pomc A (proopiomelanocortin), pomc B, GtH alpha I subunit (gonadotropin
      hormone), GtH alpha II subunit and GH (growth hormone) were present in this
      library. Comparison of the Chinese sturgeon proteins (GH, GtH alpha subunit and
      POMC) to proteins of other species showed higher levels of homology among
      sturgeon species. We performed five hormone related genes including GnRHRI
      (gonadotropin-releasing hormone receptor I), cpH (carboxypeptidase H), ppiB
      (peptidylprolyl isomerase B), stmn3 (stathmin-like 3), 7B2 (neuroendocrine
      protein 7B2), and four novel genes (contig 192, 177, 170 and 168) a semi
      quantitative RT-PCR on different tissues from Chinese sturgeon.

PMID- 21867971
TI  - Functional annotation of an expressed sequence tag library from Haliotis
      diversicolor and analysis of its plant-like sequences.
AB  - The small abalone, Haliotis diversicolor, is a widely distributed and cultured
      species in the subtropical coastal area of China. To identify and classify
      functional genes of this important species, a normalized expressed sequence tag
      (EST) library, including 7069 high quality ESTs from the total body of H.
      diversicolor, was analyzed. A total of 4781 unigenes were assembled and 2991
      novel abalone genes were identified. The GC content, codon and amino acid usage
      of the transcriptome were analyzed. For the accurate annotation of the abalone
      library, different influencing factors were evaluated. The gene ontology (GO)
      database provided a higher annotation rate (69.6%), and sequences longer than
      800bp were easily subjected to a BLAST search. The taxonomy of the BLAST results
      showed that lancelet and invertebrates are most closely related to abalone. Sixty
      seven identified plant-like genes were further examined by reverse transcription
      polymerase chain reaction (RT-PCR) and sequencing, only seven of these were real
      transcripts in abalone. Phylogenic trees were also constructed to illustrate the
      positions of two Cystatin sequences and one Calmodulin protein sequence
      identified in abalone. To perform functional classification, three different
      databases (GO, KEGG and COG) were used and 60 immune or disease-related unigenes
      were determined. This work has greatly enlarged the known gene pool of H.
      diversicolor and will have important implications for future molecular and
      genetic analyses in this organism.

PMID- 21867970
TI  - Expressed sequence tags from heat-shocked seagrass Zostera noltii (Hornemann)
      from its southern distribution range.
AB  - Predicted global climate change threatens the distributional ranges of species
      worldwide. We identified genes expressed in the intertidal seagrass Zostera
      noltii during recovery from a simulated low tide heat-shock exposure. Five
      Expressed Sequence Tag (EST) libraries were compared, corresponding to four
      recovery times following sub-lethal temperature stress, and a non-stressed
      control. We sequenced and analyzed 7009 sequence reads from 30min, 2h, 4h and 24h
      after the beginning of the heat-shock (AHS), and 1585 from the control library,
      for a total of 8594 sequence reads. Among 51 Tentative UniGenes (TUGs) exhibiting
      significantly different expression between libraries, 19 (37.3%) were identified
      as 'molecular chaperones' and were over-expressed following heat-shock, while 12
      (23.5%) were 'photosynthesis TUGs' generally under-expressed in heat-shocked
      plants. A time course analysis of expression showed a rapid increase in
      expression of the molecular chaperone class, most of which were heat-shock
      proteins; which increased from 2 sequence reads in the control library to almost
      230 in the 30min AHS library, followed by a slow decrease during further
      recovery. In contrast, 'photosynthesis TUGs' were under-expressed 30min AHS
      compared with the control library, and declined progressively with recovery time
      in the stress libraries, with a total of 29 sequence reads 24h AHS, compared with
      125 in the control. A total of 4734 TUGs were screened for EST-Single Sequence
      Repeats (EST-SSRs) and 86 microsatellites were identified.

PMID- 21867972
TI  - Transcriptome analysis in Concholepas concholepas (Gastropoda, Muricidae): mining
      and characterization of new genomic and molecular markers.
AB  - The marine gastropod Concholepas concholepas, locally known as the "loco", is the
      main target species of the benthonic Chilean fisheries. Genetic and genomic tools
      are necessary to study the genome of this species in order to understand the
      molecular basis of its development, growth, and other key traits to improve the
      management strategies and to identify local adaptation to prevent loss of
      biodiversity. Here, we use pyrosequencing technologies to generate the first
      transcriptomic database from adult specimens of the loco. After trimming, a total
      of 140,756 Expressed Sequence Tag sequences were achieved. Clustering and
      assembly analysis identified 19,219 contigs and 105,435 singleton sequences.
      BlastN analysis showed a significant identity with Expressed Sequence Tags of
      different gastropod species available in public databases. Similarly, BlastX
      results showed that only 895 out of the total 124,654 had significant hits and
      may represent novel genes for marine gastropods. From this database, simple
      sequence repeat motifs were also identified and a total of 38 primer pairs were
      designed and tested to assess their potential as informative markers and to
      investigate their cross-species amplification in different related gastropod
      species. This dataset represents the first publicly available 454 data for a
      marine gastropod endemic to the southeastern Pacific coast, providing a valuable
      transcriptomic resource for future efforts of gene discovery and development of
      functional markers in other marine gastropods.

PMID- 21867973
TI  - Intron features of key functional genes mediating nitrogen metabolism in marine
      phytoplankton.
AB  - Introns are widespread and variable in eukaryotic genomes. Although their
      histories and functions, or even whether all of them have any function, remain
      largely unknown, analysis of intron sequences and genomic contexts may shed light
      on the evolutionary history of genes and organisms. The number and frequency of
      introns vary widely in the small number of published genomes of protists and
      algae suggesting that the same is true of the vast diversity of protists and
      algae that remain uncultivated. The objective of this study were to investigate
      introns in sequences of functional genes of phytoplankton, both in published
      genomes and in sequences obtained from environmental clone libraries. We examined
      the introns of the genes involved in nitrogen uptake and assimilation pathways in
      the genome sequences of cultivated phytoplankton as well as in environmental
      clone libraries of nitrate reductases (NR), nitrite reductase (NiR), nitrate
      transporter (Nrt2) and ammonium transporter (AMT) genes constructed from pelagic
      phytoplankton communities in Monterey Bay (CA, USA) and Onslow Bay (NC, USA).
      Here we describe the most extensive set to date of intron sequences from
      uncultivated marine algae and report important differences for diatom vs. non
      diatom sequences. The majority of the introns in NR, NiR, Nrt2 and AMT from
      cultured phytoplankton and environmental libraries showed canonical splice
      patterns. Introns found in diatom-like NR environmental libraries had lower GC
      content than the respective exons. The green algal-like NR and Nrt2 environmental
      sequences had introns and exons of much more similar GC content, and both higher
      than in diatoms. These patterns suggest a different evolutionary history and
      recent acquisition of diatom introns compared to other algae.

PMID- 21867974
TI  - Comparative cytogenetics and heterochromatic patterns in two species of the genus
      Acanthostracion (Ostraciidae: Tetraodontiformes).
AB  - Some groups of fish, such as those belonging to the Order Tetraodontiformes, may
      differ significantly in the amount and location of heterochromatin in the
      chromosomes. There is a marked variation in DNA content of more than seven-fold
      among the families of this Order. However, the karyoevolutionary mechanisms
      responsible for this variation are essentially unknown. The largest genomic
      contents are present in species of the family Ostraciidae (2.20-2.60pg). The
      present study cytogenetically characterized two species of the family
      Ostraciidae, Acanthostracion polygonius and A. quadricornis, using conventional
      staining, C-bandings, Ag-NOR, CMA(3)/DAPI, AluI, PstI, EcoRI, TaqI and HinfI
      restriction enzymes (REs) and double FISH with 18S and 5S rDNA probes. The
      karyotypes of both species showed 2n=52 acrocentric chromosomes (FN=52;
      chromosome arms) and pronounced conserved structural characteristics. A
      significant heterochromatic content was observed equilocally distributed in
      pericentromeric position in all the chromosome pairs. This condition is unusual
      in relation to the karyotypes of other families of Tetraodontiformes and
      probability is the cause of the higher DNA content in Ostraciidae. Given the role
      played by repetitive sequences in the genomic reorganization of this Order, it is
      suggested that the conspicuous heterochromatic blocks, present in the same
      chromosomal position and with apparently similar composition, may have arisen or
      undergo evolutionary changes in concert providing clues about the chromosomal
      mechanisms which led to extensive variation in genomic content of different
      Tetraodontiformes families.

PMID- 21867975
TI  - The complete mitochondrial genome of the Sichuan taimen (Hucho bleekeri):
      repetitive sequences in the control region and phylogenetic implications for
      Salmonidae.
AB  - The complete mitochondrial DNA genome of the Sichuan taimen (Hucho bleekeri) was
      determined by the long and accurate polymerase chain reaction (LA-PCR) and primer
      walking sequence method. The entire mitochondrial genome of this species is
      16,997bp in length, making it the longest among the completely sequenced
      Salmonidae mitochondrial genomes. It consists of two ribosomal RNA (rRNA) genes,
      13 protein-coding genes, 22 transfer RNA (tRNA) genes, and one control region
      (CR). The gene arrangement, nucleotide composition, and codon usage pattern of
      the mitochondrial genome are similar to those of other teleosts. A T-type
      mononucleotide microsatellite and an 82bp tandem repeat were identified in the
      control region, which were almost identical among the three H. bleekeri
      individuals examined. Both phylogenetic analyses based on 12 concatenated protein
      coding genes of the heavy strand and on just the control region show that H.
      bleekeri is a basal species in Salmoninae. In addition, Salmo, Salvelinus and
      Oncorhynchus all represent monophyletic groups, respectively. All freshwater
      species occupied basal phylogenetic positions, and also possessed various tandem
      repeats in their mitochondrial control regions. These results support established
      phylogenetic relationships among genera in Salmonidae based on morphological and
      molecular analyses, and are consistent with the hypothesis that Salmonidae
      evolved from freshwater species.

PMID- 21867976
TI  - A tandem-repeat galectin involved in innate immune response of the pearl oyster
      Pinctada fucata.
AB  - The cDNA of a tandem-repeat galectin from the pearl oyster Pinctada fucata
      (designated PfGal) was cloned by expressed sequence tag (EST) and rapid
      amplification of cDNA ends (RACE) techniques. The full-length cDNA of PfGal was
      1386bp, consisting of a 5' untranslated region (UTR) of 26bp, a 3' UTR of 313bp,
      and an open reading frame (ORF) of 1047bp encoding a polypeptide of 348 amino
      acids with a predicted molecular weight of 38.09kDa and theoretical isoelectric
      point of 8.49. Similar to other tandem-repeat galectins, PfGal contained two
      tandem carbohydrate recognition domains (CRDs), with typical conserved motifs
      which were important for carbohydrate recognition, and it appeared to possess
      neither a signal peptide nor a transmembrane domain. Fluorescent quantitative
      real-time PCR analyses indicated that PfGal mRNA was highly expressed in
      hemocytes, digestive gland and mantle, and its expression was increased in all
      studied tissues after Vibrio alginolyticus challenge. The temporal expression of
      PfGal mRNA in hemocytes challenged by V. alginolyticus was clearly time-dependent
      and reached the maximum level at 6h post-challenge, and then recovered to the
      original level. These results collectively indicated that PfGal may be involved
      in the immune response against bacterial infection and clearance of bacterial
      pathogens in P. fucata.

PMID- 21867977
TI  - Prolotherapy for tissue repair.

PMID- 21867978
TI  - Effect of prolotherapy on cellular proliferation and collagen deposition in MC3T3
      E1 and patellar tendon fibroblast populations.
AB  - Proliferative therapy, or prolotherapy, is a treatment for damaged connective
      tissues involving the injection of a solution (proliferant) which causes local
      cell death and triggers the body's wound healing cascade. Physicians vary in
      their use of this technique; it is employed for ligaments but has also been
      investigated for tissues such as cartilage. Physicians also vary in treatment
      regiments using different dosses of the proliferant. This study evaluates several
      proliferant dosages develop an optimal dosage that maximizes cell and collagen
      regeneration. This study also looks at cell and collagen regeneration in response
      to proliferant exposure outside of the healing cascade. MC3T3-E1 cells and
      patellar tendon fibroblasts were exposed to various amounts of the proliferant
      P2G and monitored over several weeks. The results showed an inverse relationship
      between proliferant concentration and cell viability and collagen production in
      MC3T3-E1 cells. Following exposure, cell populations experienced an initial
      decrease in cell number followed by increased proliferation. Trichrome staining
      over 4 weeks showed an increase in collagen production after proliferant
      exposure. However the cell numbers and amounts of collagen from the treated
      groups never surpassed those of the untreated groups, although collagen
      production was comparable in fibroblasts. The results of this basic study show
      that there is an effective proliferant dosage and point to a local response to
      the proliferant that increases cell proliferation and collagen production
      separate from the wound healing cascade. This local response may not be adequate
      for complete healing and assistance from the body's healing cascade may be
      required.

PMID- 21867979
TI  - Regenerating gene Ialpha is a biomarker for diagnosis and monitoring of celiac
      disease: a preliminary study.
AB  - The regenerating gene (REG) is a multigene family in humans that plays a role in
      tissue regeneration. The REG Ialpha protein is expressed in the pancreas and the
      gastrointestinal tract and is involved in the pathophysiology of gastritis,
      pancreatitis, cancer, inflammatory bowel disease, and type 1 diabetes (T1D).
      Celiac disease (CD) is an autoimmune disease caused by the ingestion of gluten in
      genetically susceptible individuals. Our aim was to determine whether the serum
      REG Ialpha concentration reflects the destructive/regenerative process in the
      small bowel in CD. REG Ialpha was determined by enzyme-linked immunosorbent assay
      (ELISA) in 40 patients with active CD, and in 19 of them, REG Ialpha was assessed
      after following a gluten free diet. As controls, 35 healthy subjects were
      included in the study. Autoantibodies to transglutaminase, gliadin, and
      endomisium were measured also. We found a significant increase in REG Ialpha in
      the sera of CD patients when compared with controls. REG Ialpha levels decreased
      after a gluten-free diet together with a significant reduction in
      antitransglutaminase antibodies. T1D and pernicious anemia patients displayed
      normal serum REG Ialpha concentrations. This preliminary study suggests that REG
      Ialpha protein levels can be used as a biomarker for the diagnosis and monitoring
      of CD.

PMID- 21867980
TI  - Cellular localization of NKCC2 and its possible role in the Cl- absorption in the
      rat and human distal colonic epithelia.
AB  - Recently, we demonstrated the expression of NKCC2, an absorptive isoform of NKCC
      specifically expressed in the kidney, in the rat gastrointestinal tract including
      the distal colonic mucosa. This study aims to investigate its localization in
      colonic epithelia and possible role in the colonic ion transport. Reverse
      transcription polymerase chain reaction (RT-PCR), Western blotting, and
      immunohistochemistry were used to investigate the expression and localization of
      NKCC2. The role of NKCC2 on the colonic ion transport was examined by mean of
      short-circuit current (I(SC)) monitoring. The results indicated that NKCC2 was
      expressed in the apical region of the epithelia in rat distal colon and human
      sigmoid colon. NKCC1, which is a secretive NKCC isoform, was localized
      predominantly in the basolateral membrane, which has been well documented.
      Serosal (basolateral) administration of bumetanide, an inhibitor of both NKCC1
      and NKCC2, inhibited serosal forskolin-induced I(SC) increase by 66% but enhanced
      the luminal (apical) forskolin-induced I(SC) response by 63%. Furthermore, the
      blocking of epithelial Na(+) channels by apical addition of amiloride (10
      MUmol/L), K(+) channels by tetraethylammoniumion (TEA) (5 mmol/L), or
      glibenclimide (0.1 mmol/L) did not affect apical forskolin-induced I(SC)
      increase, excluding the involvement of cations, Na(+) and K(+), in the I(SC)
      response. The luminal forskolin-induced I(SC) increase was enhanced markedly by
      the apical pretreatment with bumetanide or the reduction of apical Cl(-)
      concentration by 114% and 198%, respectively, which were inhibited by apical
      addition of glibenclimide (1 mmol/L) by more than 60%. This finding suggests the
      involvement of an anion. Furthermore, the removal of basolateral HCO(3)(-)
      reduced apical forskolin-induced I(SC) by more than 75% indicated that the apical
      forskolin-induced I(SC) increase in rat distal colon was mediated by Cl(-)
      absorption and HCO(3)(-) secretion. In conclusion, NKCC2 is expressed widely in
      the colonic epithelium in rat distal colon and human sigmoid colon, especially in
      the apical membrane. It involves the process of colonic Cl(-) absorption coupled
      with HCO(3)(-) secretion.

PMID- 21867981
TI  - Relation of serum insulin-like growth factor-1 (IGF-1) levels with hepatitis C
      virus infection and insulin resistance.
AB  - The prospect of the growing worldwide epidemic of hepatitis C virus (HCV)
      infection and type 2 diabetes mellitus certainly merits attention toward their
      controversial relationship. Insulin-like growth factor-1 (IGF-1) plays an
      important role in glucose homeostasis. This study is a cross-sectional study
      considered as an initial investigation aimed to evaluate the effect of HCV
      infection on serum IGF-1, as well as to find out whether IGF-1 has a role in
      development of insulin resistance (IR) in HCV infection. A total of 45 subjects
      divided into 3 groups were included in the study: chronic HCV-infected patients
      (15 patients), chronic HCV-infected diabetic patients (15 patients), and diabetic
      patients without HCV infection (15 patients), along with 15 healthy controls. HCV
      RNA was quantified using real-time polymerase chain reaction (PCR). Serum IGF-1
      levels were measured by enzyme-linked immunosorbent assay (ELISA). Homeostasis
      model assessment of insulin resistance [HOMA-IR], insulin sensitivity [HOMA-S],
      and beta-cell function [HOMA-beta] were determined by previously validated
      mathematic indexes. Fasting blood glucose, insulin levels, and liver parameters
      including alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      were determined. IGF-1 levels were significantly lower in the 3 patient groups
      compared with controls (P = 0.001). The HCV group demonstrated high HOMA-IR and
      HOMA-beta with a positive correlation between HOMA-IR and either HOMA-beta or
      fasting insulin (P < 0.001). In addition, a negative correlation was found
      between IGF-1 levels and both AST and ALT, and HOMA-IR was correlated positively
      with AST activity (P < 0.05). In HCV patients with detectable viremia, IGF-1
      levels were correlated negatively with HOMA-beta (P < 0.01) and with HOMA-IR.
      However, this correlation did not reach statistical significance (P = 0.074). No
      significant correlation was found between HCV viral load and the studied
      parameters. In conclusion, low IGF-I levels might have a role in IR among HCV
      viremic patients.

PMID- 21867982
TI  - Intersession repeatability of a novel nasal lavage technique.
AB  - This study describes a novel nasal lavage method using a pediatric tracheostomy
      tube and examines intersession repeatability for several clinically and
      technically relevant parameters. Fourteen healthy subjects were included in this
      study. Both nasal cavities were washed using a standard amount of saline solution
      (7 mL) via a pediatric tracheostomy tube, and the 2 samples were pooled for
      measurement of cytokine concentrations and cell count. Recovery volume was also
      recorded. For each subject, measurements were repeated on 5 consecutive days.
      Intersession repeatability of recovery volume, cell count, and cytokine
      concentrations interleukin (IL)-6 and IL-8 were expressed in terms of mean
      coefficient of variation, intraclass correlation coefficient, and interitem
      correlations. Intraclass correlation coefficients and interitem correlation
      coefficients indicated almost perfect agreement for cell count and IL-8
      concentrations. Recovery volume and IL-6 concentrations were more variable. The
      mean coefficient of variation was low for cell count (2%), IL-8 concentration
      (3%), and recovery volume (3%), whereas the mean percentage recovery was high
      (87%). This newly developed nasal lavage technique is repeatable over successive
      sessions for cytokine concentrations and cell counts in nasal secretions of
      healthy subjects. This method might be valuable in the study of inflammatory
      conditions involving the upper respiratory tract.

PMID- 21867983
TI  - Comparative quantitative analysis of BCR-ABL transcripts with the T315I mutant
      clone by polymerase chain reaction (PCR)-Invader method.
AB  - Drug resistance is a serious complication in the treatment of chronic myeloid
      leukemia (CML). The most common and best-characterized mechanism of secondary
      imatinib resistance in CML is the development of kinase domain mutations in the
      BCR-ABL gene. Second-generation tyrosine kinase inhibitors, such as dasatinib or
      nilotinib, overcome most of these mutations, but they are not effective against
      the T315I mutant. To determine whether these mutations contribute to clinical
      resistance, it is necessary to monitor the ratio of the mutant and wild-type
      forms. Here, we developed a polymerase chain reaction (PCR)-Invader assay for
      comparative quantitative analysis (qPI assay) of BCR-ABL transcripts with the
      T315I mutant clone. T315I ratios were calculated for the wild-type and mutant
      fold-over-zero (FOZ) values. In examination with 2 kinds of plasmids containing
      wild-type or T315I mutant PCR amplicons, mutant FOZ values were detected down to
      1% of the total. The results of 12 serial samples from 2 patients (case A:
      Philadelphia-positive acute lymphoblastic leukemia and case B: CML) with the
      T315I mutant clone were compared with those of direct sequencing or 2 kinds of
      allele-specific oligonucleotide (ASO)-PCR. All samples showed the T315I mutation
      by qPI assay and ASO-PCR, and 10 samples showed it by direct sequencing.
      Significant correlation (correlation coefficient; r2 = 0.951) was noted between
      the qPI assay and quantitative ASO-PCR to analyze T315I mutant ratios. Thus, the
      qPI assay is a useful method for evaluating the T315I mutant clone in BCR-ABL
      transcripts.

PMID- 21867984
TI  - Reactions of dipolar bio-molecules in nano-capsules--example of folding-unfolding
      process.
AB  - The confinement of chemical reactions in nano-capsules can lead to a dramatic
      effect on the equilibrium constant of these latter. Indeed, capillary effects due
      to the curvature and surface energy of nano-capsules can alter in a noticeable
      way the evolution of reactions occurring within. Nano-encapsulation of bio
      materials has attracted lately wide interest from the scientific community
      because of the great potential of its applications in biomedical areas and
      targeted therapies. The present paper focuses one's attention on alterations of
      conformation mechanisms due to extremely confining and interacting solvated
      dipolar macromolecules at their isoelectric point. As a specific example studied
      here, the folding-unfolding reaction of proteins (particularly RNase A and
      creatine kinase CK) is drastically changed when encapsulated in solid inorganic
      hollow nano-capsules. The effects demonstrated in this work can be extended to a
      wide variety of nano-encapsulation situations. The design and sizing of nano
      capsules can even make use of the effects shown in the present study to achieve
      better and more effective encapsulation.

PMID- 21867985
TI  - [Serum albumin and heart failure: recent advances on a new paradigm].
AB  - Hypoalbuminemia is a common condition in patients with heart failure and is
      mainly related to the malnutrition-inflammation complex syndrome. Other causal
      factors can be involved, which include hemodilution, liver dysfunction, increased
      transcapillary escape rate, renal and enteral loss. Evidence is growing that
      hypoalbuminemia independently predicts incident heart failure in patients with
      end-stage renal disease and elderly patients, as well as mortality in patients
      with heart failure regardless of left ventricular ejection fraction and clinical
      presentation. Hypoalbuminemia induces a low plasma oncotic pressure, which
      facilitates pulmonary edema in patients without critical increase in pulmonary
      capillary hydrostatic pressures. Hypoalbuminemia may also contribute to the
      progression of heart failure by favoring myocardial edema, volume overload,
      diuretic resistance and exacerbation of oxidative stress and inflammation. If
      relevant, removal of subclinical excess of fluid and renutrition may be indicated
      in patients with heart failure and hypoalbuminemia. Additional research is
      warranted to determine the specific role of serum albumin in the pathophysiologic
      process of heart failure and the potential benefits of targeted therapeutic
      interventions.

PMID- 21867986
TI  - Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell
      neuroendocrine carcinomas: a single institution experience.
AB  - BACKGROUND: Pulmonary large cell neuroendocrine carcinomas (LCNEC) are aggressive
      neoplasms with poor prognosis. The role of neoadjuvant and adjuvant therapies in
      these tumors remains uncertain. METHODS: We performed a retrospective review of a
      prospective database. Kaplan-Meier estimates of overall survival (OS) were
      determined and compared across prognostic factors using log-rank analysis and the
      Cox proportional hazards model. RESULTS: One hundred patients with resected LCNEC
      were identified from 1992 to 2008. Of these, 54% were male and 98% current or
      former smokers (mean 60.3 pack-years). Twenty-two patients received neoadjuvant
      platinum chemotherapy with a response rate of 68% (15 of 22). Eighty percent (80
      of 100) underwent lobectomy and 11% (11 of 100) pneumonectomy with a 90% (90 of
      100) complete resection (R0) rate. Seventy-one percent (71 of 100) were stage I
      II, and 20 of 71 received platinum adjuvant chemotherapy. Mean OS was 40 months.
      Univariate factors associated with decreased OS included male gender (p = 0.007),
      increasing tumor (T) stage (p = 0.004), and stage III-IV disease (p = 0.04).
      Stage IB patients fared significantly worse than IA (p = 0.006). Multivariate
      analyses identified male gender (hazard ratio [HR] 2.3, p = 0.007), comorbid
      pulmonary disease (HR 2.3, p = 0.012), and pathologic stage (HR = 2.2, p = 0.011)
      as associated with risk of death. Univariate analysis in stage IB-IIIA completely
      resected (R0) patients receiving combination platinum-based induction and (or)
      adjuvant chemotherapy showed a trend toward improved OS (median survival 7.4 vs 2
      years, p = 0.052). CONCLUSIONS: The LCNEC has a high response rate to platinum
      based neoadjuvant chemotherapy. Resected advanced-stage patients receiving
      combination neoadjuvant and (or) adjuvant chemotherapy may have a survival
      advantage. These therapies should be considered in resectable patients with
      LCNEC.

PMID- 21867987
TI  - Increased ascending aortic wall stress in patients with bicuspid aortic valves.
AB  - BACKGROUND: Patients with bicuspid aortic valves (BAV) are at increased risk of
      ascending aortic dilatation, dissection, and rupture. We hypothesized that
      ascending aortic wall stress may be increased in patients with BAV compared with
      patients with tricuspid aortic valves (TAV). METHODS: Twenty patients with BAV
      and 20 patients with TAV underwent electrocardiogram-gated computed tomographic
      angiography. Patients were matched for diameter. The thoracic aorta was
      segmented, reconstructed, and triangulated to create a mesh. Utilizing a uniform
      pressure load of 120 mm Hg, and isotropic, incompressible, and linear elastic
      shell elements, finite element analysis was performed to predict 99th percentile
      wall stress. RESULTS: For patients with BAV and TAV, aortic root diameter was 4.0
      +/- 0.6 cm and 4.0 +/- 0.6 cm (p = 0.724), sinotubular junction diameter was 3.6
      +/- 0.8 cm and 3.6 +/- 0.7 cm (p = 0.736), and maximum ascending aortic diameter
      was 4.0 +/- 0.8 cm and 4.1 +/- 0.9 cm (p = 0.849), respectively. The mean 99 th
      percentile wall stress in the BAV group was greater than in the TAV group (0.54
      +/- 0.06 MPa vs 0.50 +/- 0.09 MPa), though this did not reach statistical
      significance (p = 0.090). When normalized by radius, the 99 th percentile wall
      stress was greater in the BAV group (0.31 +/- 0.06 MPa/cm vs 0.27 +/- 0.03
      MPa/cm, p = 0.013). CONCLUSIONS: Patients with BAV, regardless of aortic
      diameter, have increased 99 th percentile wall stress in the ascending aorta.
      Ascending aortic three-dimensional geometry may account in part for the increased
      propensity to aortic dilatation, rupture, and dissection in patients with BAV.

PMID- 21867988
TI  - Long-term clinical impact of functional mitral regurgitation after aortic valve
      replacement.
AB  - BACKGROUND: We evaluated the impact of functional mitral regurgitation (MR) on
      clinical outcomes and to identify predictors of residual MR after aortic valve
      replacement in aortic stenosis. METHODS: Three hundred and eighty-four patients
      who underwent primary aortic valve replacement for aortic stenosis were enrolled.
      Patients were divided into the no-MR group (no or trivial MR; n = 270) and the MR
      group (mild to moderate MR; n = 114). In the MR group, 19 patients underwent
      concomitant mitral valve repairs. Mean follow-up duration was 4.5 +/- 3.7 years
      (range, 1 to 15 years). Clinical and echocardiographic data were analyzed.
      RESULTS: There was no operative mortality, but there were 9 late cardiac deaths
      (2.3%). Freedom from cardiac death at 14 years was lower in the MR group than in
      the no-MR group (77.8% +/- 12.6% versus 97.7% +/- 1.4%, respectively; p = 0.045),
      and freedom from heart failure events at 10 years was also lower in the MR group
      (60.8% +/- 13.4% versus 92.6% +/- 2.2%, p = 0.043). On multivariate analysis,
      preoperative atrial fibrillation and left ventricular ejection fraction greater
      than 40% were predictors for residual MR at late follow-up in the untreated MR
      group. Cox regression analysis demonstrated that postoperative moderate MR
      predicted late cardiac death (p = 0.016, hazard ratio 5.2). In the MR group, the
      incidence of residual MR in patients who underwent mitral valve repair was 5.6%
      (versus 30.7% in patients without mitral valve repair, p = 0.001). CONCLUSIONS:
      Functional MR in aortic stenosis was related to poor clinical outcomes. The
      results of this study suggest that concomitant mitral valve procedures could be
      considered in selected patients with aortic stenosis and functional MR.

PMID- 21867989
TI  - Repeated and aggressive pulmonary resections for leiomyosarcoma metastases
      extends survival.
AB  - BACKGROUND: Sarcoma frequently metastasizes to the lungs, and pulmonary
      metastasectomy is the only treatment modality that can provide a cure for these
      patients. We attempted to determine the clinicopathologic features and survival
      determinants of a common subset of patients who undergo pulmonary metastasectomy
      for leiomyosarcoma. METHODS: All patients undergoing pulmonary metastasectomy at
      The Brigham and Women's Hospital from 1989 to 2004 were reviewed retrospectively.
      Analyzed variables included number, size, pathology, and location of metastases,
      age, gender, location of primary tumor, disease-free interval (DFI), surgical
      approach, margin status, adjuvant therapy, recurrence, number of
      metastasectomies, and disease-free and overall survival. RESULTS: Eighty-two
      patients underwent pulmonary metastasectomy for metastases from sarcoma.
      Leiomyosarcoma was the most common histologic finding (n = 31; 38%). Fifteen
      patients with leiomyosarcoma (48%) underwent repeated pulmonary metastasectomy.
      Patients with leiomyosarcoma were more commonly female (77% versus 43%; p =
      0.031), less frequently received chemotherapy for their primary tumor (48% versus
      71%, p = 0.041), and presented with fewer number of pulmonary metastases than did
      patients with nonleiomyosarcoma metastases (1.9 +/- 1.5 standard deviation [SD]
      versus 3.6 +/- 4.4; p = 0.033). Although there was no difference in disease-free
      survival, patients with leiomyosarcoma demonstrated improved overall survival
      compared with those with nonleiomyosarcoma metastases (70 versus 24 months; p =
      0.049). In multivariate analyses, the DFI from primary tumor resection to
      pulmonary metastases and the DFI from pulmonary metastasectomy to second
      pulmonary recurrence were identified as independent predictors of survival.
      CONCLUSIONS: Leiomyosarcoma is a common subset of sarcomatous pulmonary
      metastases that behave more indolently compared with other pulmonary metastases
      from sarcoma. Long-term survival is achievable with an aggressive approach toward
      pulmonary metastasectomy and repeated pulmonary metastasectomy.

PMID- 21867990
TI  - The effect of a multidisciplinary thoracic malignancy conference on the treatment
      of patients with esophageal cancer.
AB  - BACKGROUND: There is a paucity of data evaluating whether a multidisciplinary
      conference coordinating surgery, chemotherapy and radiation therapy translates
      into better patient care. This review compares the experiences of patients with
      esophageal cancer before and after the formation of a prospective,
      multidisciplinary thoracic malignancy conference (TMC). METHODS: The records of
      patients with carcinoma of the esophagus at a tertiary care hospital were
      reviewed for completeness of staging, multidisciplinary evaluation before the
      initiation of therapy, time from pathologic diagnosis to treatment, multimodality
      therapy, and adherence to national treatment guidelines. Summary data were
      compared for patients treated before and after the TMC was initiated. RESULTS:
      Between 2001 and 2007, 117 patients were treated before the initiation of the TMC
      and 138 patients within the TMC. The number of patients receiving, respectively,
      a complete staging evaluation (67% and 97%, p < 0.0001), multidisciplinary
      evaluation before therapy (72% and 98%, p < 0.0001), and adherence to National
      Comprehensive Cancer Network treatment guidelines (83% and 98%, p < 0.0001) all
      increased significantly, whereas mean days from diagnosis to treatment
      significantly decreased (27 and 16, respectively; p < 0.0001). CONCLUSIONS: A
      multidisciplinary TMC increased the percentage of patients receiving complete
      staging, a multidisciplinary evaluation, and adherence to nationally accepted
      care guidelines while decreasing the interval from diagnosis to treatment
      significantly. While the ultimate goal of treatment is to improve patient
      survival, the surrogate variables examined in this review indicate that patients
      with esophageal cancer benefit from being evaluated in a prospective,
      multidisciplinary manner.

PMID- 21867991
TI  - Reduced right ventrolateral prefrontal cortex activity while inhibiting positive
      affect is associated with improvement in hedonic capacity after 8 weeks of
      antidepressant treatment in major depressive disorder.
AB  - BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief
      symptom of major depressive disorder and is related to reduced frontostriatal
      connectivity when attempting to upregulate positive emotion. The present study
      examined another facet of positive emotion regulation associated with anhedonia
      namely, the downregulation of positive affect-and its relation to prefrontal
      cortex (PFC) activity. METHODS: Neuroimaging data were collected from 27
      individuals meeting criteria for major depressive disorder as they attempted to
      suppress positive emotion during a positive emotion regulation task. Their PFC
      activation pattern was compared with the PFC activation pattern exhibited by 19
      healthy control subjects during the same task. Anhedonia scores were collected at
      three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and
      6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was
      used to predict change in anhedonia over time. Analyses were conducted utilizing
      hierarchical linear modeling software. RESULTS: Depressed individuals who could
      not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal
      cortex activity during attempts to dampen their experience of positive emotion in
      response to positive visual stimuli-exhibited a steeper anhedonia reduction slope
      between baseline and 8 weeks of treatment with antidepressant medication (p <
      .05). Control subjects showed a similar trend between baseline and time 3.
      CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to
      counteract the functioning of an overactive pleasure-dampening prefrontal
      inhibitory system.

PMID- 21867992
TI  - Structural studies of the O-antigenic polysaccharide from Escherichia coli O177.
AB  - The structure of the O-antigen polysaccharide (PS) from Escherichia coli O177 has
      been determined. Component analysis together with (1)H and (13)C NMR spectroscopy
      experiments was used to determine the structure. Inter-residue correlations were
      determined by (1)H,(13)C-heteronuclear multiple-bond correlation and (1)H,(1)H
      NOESY experiments. PS is composed of tetrasaccharide repeating units with the
      following structure: ->2)-alpha-L-Rhap-(1->3)-alpha-L-FucpNAc-(1->3)-alpha-L
      FucpNAc-(1->3)-beta-D-GlcpNAc-(1->. An alpha-L-Rhap residue is suggested to be
      present at the terminal part of the polysaccharide, which on average is composed
      of ~20 repeating units, since the (1)H and (13)C chemical shifts of an alpha
      linked rhamnopyranosyl group could be assigned by a combination of 2D NMR
      spectra. Consequently, the biological repeating unit has a 3-substituted N-acetyl
      D-glucosamine residue at its reducing end. The repeating unit of the E. coli O177
      O-antigen shares the ->3)-alpha-L-FucpNAc-(1->3)-beta-D-GlcpNAc-(1-> structural
      element with the O-antigen from E. coli O15 and this identity may then explain
      the reported cross-reactivity between the strains.

PMID- 21867993
TI  - Bimutation breeding of Aspergillus niger strain for enhancing beta-mannanase
      production by solid-state fermentation.
AB  - A parent strain Aspergillus niger LW-1 was mutated by the compound mutagenesis of
      vacuum microwave (VMW) and ethyl methane sulfonate (EMS). A mutant strain,
      designated as A. niger E-30, with high- and stable-yield beta-mannanase was
      obtained through a series of screening. The beta-mannanase activity of the mutant
      strain E-30, cultivated on the basic fermentation medium at 32 degrees C for 96
      h, reached 36,675 U/g dried koji, being 1.98-fold higher than that (18,50 1U/g
      dried koji) of the parent strain LW-1. The purified E-30 beta-mannanase, a
      glycoprotein with a carbohydrate content of 19.6%, had an apparent molecular
      weight of about 42.0 kDa by SDS-PAGE. Its optimal pH and temperature were 3.5 and
      65 degrees C, respectively. It was highly stable at a pH range of 3.5-7.0 and at
      a temperature of 60 degrees C and below. The kinetic parameters K(m) and V(max),
      toward locust bean gum and at pH 4.8 and 50 degrees C, were 3.68 mg/mL and 1067.5
      U/mg, respectively. The beta-mannanase activity was not significantly affected by
      an array of metal ions and EDTA, but strongly inhibited by Ag(+) and Hg(2+). In
      addition, the hydrolytic conditions of konjak glucomannan using the purified E-30
      beta-mannanase were optimized as follows: konjak gum solution 240 g/L (dissolved
      in deionized water), hydrolytic temperature 50 degrees C, beta-mannanase dosage
      120 U/g konjak gum, and hydrolytic time 8 h.

PMID- 21867994
TI  - Collective sampling of intact anionic polysaccharide components and application
      in quantitative determination by LC-MS.
AB  - Anionic polysaccharides, such as glycosaminoglycans (GAGs) and alginate, readily
      undergo source-induced fragmentation when analyzed by electrospray mass
      spectrometry with the use of high source cone voltage. The dissociation chemistry
      converts all components of a polysaccharide into a small set of structurally
      characteristic small saccharides. This chemistry enables the collective detection
      of a polysaccharide through the detection of one or more small saccharides. This
      ability, combined with the elution of polysaccharides as relatively compact bands
      using ion-pairing reverse phase liquid chromatography, created a unique
      opportunity for the development of LC-MS methods suitable for the quantitative
      analysis of intact anionic polysaccharides. Feasibility of this approach is
      demonstrated with a mixture of heparin, chondroitin sulfate A, and alginate.

PMID- 21867995
TI  - [Thyroid suppression in patients with primary hyperparathyroidism: does it
      improve the pre-surgical scintigraphy localisation?].
AB  - INTRODUCTION: Scintigraphy with technetium-sestamibi (MIBI) is the test of choice
      for localising adenomas in patients with primary hyperparathyroidism (PHPT). In
      some studies it has emerged that the increase in sensitivity of this test could
      be associated with a decrease in the uptake of the radiotracer by the thyroid
      gland. The aim of this study is to analyse our experience in patients with a
      negative scintigraphy with MIBI, and in whom the study was repeated after
      suppression of thyroid function with thyroxine. MATERIAL AND METHODS: A
      prospective evaluation was performed on 17 patients who, between January 2006 and
      April 2011, had PHPT and negative imaging using scintigraphy with MIBI and who
      had the test repeated after the administration of thyroxine. The scintigraphy
      data and the correlation with the findings in the surgical intervention are
      reviewed. RESULTS: The mean TSH at the time of repeating the MIBI was
      0.12+0.1mlU/L. Of the 17 patients included, the scintigraphy under thyroid
      suppression was positive in 13 of them (76.5%), and in the other 4 (23.5%)
      patients no image suggestive of adenoma was found. In the cases where the MIBI
      was positive after suppression, the positive predictive value (PPV) was 100%.
      CONCLUSION: Suppression of thyroid function by giving thyroxine can help to
      improve the sensitivity of MIBI in patients with previously negative scintigraphy
      studies and help in the minimally invasive treatment of patients with PHPT.

PMID- 21867996
TI  - Clinical impact of FDG PET-CT in patients with potentially operable metastatic
      colorectal cancer.
AB  - AIM: To assess the clinical impact of 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG)
      positron-emission tomography-computed tomography (PET-CT) in patients with
      potentially resectable metastatic colorectal cancer. MATERIALS AND METHODS: One
      hundred and two patients with potentially resectable metastatic colorectal cancer
      underwent FDG PET-CT in addition to conventional imaging over an 18-month period.
      The findings were compared to conventional imaging, with histological or clinico
      radiological validation. The impact on subsequent management was evaluated using
      information from clinico-radiological databases. RESULTS: Of 102 patients (mean
      age 67 years, range 27-85 years), 94 had liver, five had isolated lung, and three
      had limited peritoneal metastases. In 31 patients (30%) PET-CT had a major impact
      on subsequent management, by correctly clarifying indeterminate lesions on
      conventional imaging as inoperable metastatic disease in 16 patients, detecting
      previously unsuspected metastatic disease in nine patients, identifying occult
      second primary tumours in three patients, and correctly down-staging three
      patients. PET-CT had a minor impact in 12 patients (12%), no impact in 49 cases
      (48%), and a potentially negative impact in 10 cases (10%). Following PET-CT, 36
      (35%) patients were no longer considered for surgery. Of those remaining
      operative 45 of 66 (68%) underwent potentially curative metastatic surgery. In
      this cohort PET-CT saved 16 futile laparotomies. CONCLUSION: FDG PET-CT has a
      valuable role in selected patients with metastatic colorectal cancer by improving
      staging accuracy and characterizing indeterminate lesions and helps triage
      patients to the appropriate treatment.

PMID- 21867997
TI  - A phenomenological investigation of women with Tourette or other chronic tic
      disorders.
AB  - There are little data concerning clinical characteristics of women with Tourette
      disorder and chronic tic disorders in the extant literature and what is available
      mostly focuses on treatment-seeking individuals. The present research was
      conducted to provide a phenomenological characterization of tic disorders among
      185 adult women with tic disorders. In addition to providing a descriptive
      overview of specific tic symptoms, tic severity, self-reported history of other
      psychiatric conditions, and impairment/lifestyle impact due to tics, this study
      compares 185 women and 275 men between 18 and 79 years old with tic disorders
      (who completed an identical battery of measures) based on demographic,
      social/economic status indicators, psychiatric variables (comorbidity, family
      psychiatric history, symptom presentation), adaptive functioning/quality of life,
      and impairment variables among a nonclinical adult sample. Finally, this research
      examines the relationship between tic severity and impairment indicators among
      women with tics. Sixty-eight percent of women in our sample reported severe motor
      tics and 40% reported severe phonic tics. Our exploratory data suggest that a
      sizeable number of adult women with persistent tics are suffering from
      psychiatric comorbidity and psychosocial consequences such as underachievement
      and social distress. Tic severity in women may be associated with lifestyle
      interference as well as with symptoms of depression and anxiety, and such
      symptoms may be more common among women with tics than in men with tics.

PMID- 21867998
TI  - Quantification of total mercury in liver and heart tissue of Harbor Seals (Phoca
      vitulina) from Alaska USA.
AB  - This study quantified the Hg levels in the liver (n=98) and heart (n=43) tissues
      of Harbor Seals (Phoca vitulina) (n=102) harvested from Prince William Sound and
      Kodiak Island Alaska. Mercury tissue dry weight (dw) concentrations in the liver
      ranged from 1.7 to 393 ppm dw, and in the heart from 0.19 to 4.99 ppm dw. Results
      of this study indicate liver and heart tissues' Hg ppm dw concentrations
      significantly increase with age. Male Harbor Seals bioaccumulated Hg in both
      their liver and heart tissues at a significantly faster rate than females. The
      liver Hg bioaccumulation rates between the harvest locations Kodiak Island and
      Prince William Sound were not found to be significantly different. On adsorption
      Hg is transported throughout the Harbor Seal's body with the partition
      coefficient higher for the liver than the heart. No significant differences in
      the bio-distribution (liver:heart Hg ppm dw ratios (n=38)) values were found with
      respect to either age, sex or geographic harvest location. In this study the age
      at which Hg liver and heart bioaccumulation levels become significantly distinct
      in male and female Harbor Seals were identified through a Tukey's analysis. Of
      notably concern to human health was a male Harbor Seal's liver tissue harvested
      from Kodiak Island region. Mercury accumulation in this sample tissue was
      determined through a Q-test to be an outlier, having far higher Hg concentrarion
      (liver 392Hgppmdw) than the general population sampled.

PMID- 21867999
TI  - Body mass index-associated differences in response to ovulation induction with
      letrozole.
AB  - OBJECTIVE: To compare occurrence of pregnancy among obese (body mass index [BMI]
      >=30) and nonobese (BMI <30), infertile women undergoing ovulation induction with
      the aromatase inhibitor letrozole followed by intrauterine insemination (IUI).
      DESIGN: Retrospective cohort study. SETTING: Academic reproductive endocrinology
      and infertility clinic. PATIENT(S): Ninety women with a variety of infertility
      diagnoses. INTERVENTION(S): Letrozole (5 mg) on menstrual cycle days 3-7,
      followed by intrauterine insemination (IUI). MAIN OUTCOME MEASURE(S): Occurrence
      of pregnancy and pregnancy outcomes. RESULT(S): Ninety women underwent 180
      letrozole-IUI cycles. Conception of pregnancy occurred in 10.4% and 18.2% of the
      BMI <30 and BMI >=30 groups, respectively. Using BMI as a continuous variable
      showed a pregnancy odds ratio of 1.093 (confidence interval 1.008-1.184) for each
      unit increase in BMI. Incidence of miscarriage, multiple births, number of mature
      follicles, and presence of LH surge were similar between groups. CONCLUSION(S):
      Our study of 90 women undergoing letrozole-IUI treatment showed greater
      likelihood of pregnancy in higher-BMI women, although the difference was not
      significant. Letrozole is an effective ovulation induction agent in higher-BMI
      women.

PMID- 21868000
TI  - In vitro fertilization patients support a single blastocyst transfer policy.
AB  - OBJECTIVE: To determine whether patients support a mandatory single blastocyst
      transfer (mSBT) policy in IVF. DESIGN: Prospective survey study. SETTING:
      Academic hospital-based infertility center. PATIENT(S): Two hundred sixty-two
      female patients presenting for fresh or cryopreserved/thawed ET after IVF.
      INTERVENTION(S): Internet-based in-clinic survey after ET. Follow-up at-home
      survey after pregnancy test results. MAIN OUTCOME MEASURE(S): Patient support for
      an mSBT policy and attitudes regarding patient input into IVF treatment. Logistic
      regression analyses tested associations among main outcome measures, patient
      characteristics, and treatment results. RESULT(S): Ninety-four percent of
      patients endorsed support for our mSBT policy; 95% and 87% felt they had the
      right amount of input in their IVF treatment and number of embryos transferred,
      respectively, and these subjects were more likely to support the mSBT policy.
      Other factors associated with stronger support were concern for multiples,
      availability of extra cryopreserved embryos, and shorter duration of infertility.
      Receiving a single blastocyst during treatment did not change the level of
      support. A negative pregnancy outcome decreased support, however. CONCLUSION(S):
      Policies restricting the number of embryos transferred may find wide patient
      acceptance.

PMID- 21868001
TI  - Cost effectiveness of ovarian reserve testing in in vitro fertilization: a Markov
      decision-analytic model.
AB  - OBJECTIVE: To compare the cost effectiveness of ovarian reserve testing in in
      vitro fertilization (IVF). DESIGN: A Markov decision model based on data from the
      literature and original patient data. SETTING: Decision analytic framework.
      PATIENT(S): Computer-simulated cohort of subfertile women aged 20 to 45 years who
      are eligible for IVF. INTERVENTION(S): [1] No treatment, [2] up to three cycles
      of IVF limited to women under 41 years and no ovarian reserve testing, [3] up to
      three cycles of IVF with dose individualization of gonadotropins according to
      ovarian reserve, and [4] up to three cycles of IVF with ovarian reserve testing
      and exclusion of expected poor responders after the first cycle, with no
      treatment scenario as the reference scenario. MAIN OUTCOME MEASURE(S): Cumulative
      live birth over 1 year, total costs, and incremental cost-effectiveness ratios.
      RESULT(S): The cumulative live birth was 9.0% in the no treatment scenario, 54.8%
      for scenario 2, 70.6% for scenario 3 and 51.9% for scenario 4. Absolute costs per
      woman for these scenarios were ?0, ?6,917, ?6,678, and ?5,892 for scenarios 1, 2,
      3, and 4, respectively. Incremental cost-effectiveness ratios (ICER) for
      scenarios 2, 3, and 4 were ?15,166, ?10,837, and ?13,743 per additional live
      birth. Sensitivity analysis showed the model to be robust over a wide range of
      values. CONCLUSION(S): Individualization of the follicle-stimulating hormone dose
      according to ovarian reserve is likely to be cost effective in women who are
      eligible for IVF, but this effectiveness needs to be confirmed in randomized
      clinical trials.

PMID- 21868002
TI  - A novel missense mutation in the high mobility group domain of SRY drastically
      reduces its DNA-binding capacity and causes paternally transmitted 46,XY complete
      gonadal dysgenesis.
AB  - OBJECTIVE: To investigate the familial segregation, role, and function of a novel
      SRY missense mutation c.347T>C in two half-sisters affected by 46,XY complete
      gonadal dysgenesis (CDG) compatible with a successful pregnancy outcome. DESIGN:
      Phenotypic, mutational, and functional study. SETTING: Academic research unit.
      PATIENT(S): Two half-sisters, their common father, and 100 healthy control
      individuals. INTERVENTION(S): Chromosome, molecular cytogenetic analysis, and
      Sanger sequencing of the SRY gene in blood lymphocytes of the proband, her
      affected half-sister, and in inflammatory tissue of the father postmortem.
      Cloning and expression of high mobility group box carboxy-terminal domains of Sry
      and electrophoretic mobility shift assay were performed. MAIN OUTCOME MEASURE(S):
      Not applicable. RESULT(S): A novel SRY missense mutation c.347T>C (p.Leu116Ser)
      was identified in two half-sisters and segregates with the CGD phenotype. It is
      present in the common healthy father in a mosaic state. Functional analyses
      demonstrate the pathogenic effect of the mutation by a strong reduction of DNA
      affinity for the mutant p.Leu116Ser SRY protein. CONCLUSION(S): The missense
      mutation c.347T>C in the high mobility group domain of SRY causes 46,XY CGD.
      Paternal gonadal mosaicism is likely to explain the familial occurrence of 46,XY
      CGD suggesting a de novo mutational event during the early stages of embryonic
      development. This novel mutation is compatible with a successful pregnancy
      outcome.

PMID- 21868003
TI  - Clinical outcome of non-hCG-primed oocyte in vitro maturation treatment in
      patients with polycystic ovaries and polycystic ovary syndrome.
AB  - OBJECTIVE: To compare clinical outcomes of fresh embryo transfer (ET) and
      vitrified-warmed ET in an artificial endometrial priming cycle in patients with
      polycystic ovaries (PCO) or polycystic ovary syndrome (PCOS) who underwent oocyte
      in vitro maturation (IVM) in non-hCG-primed cycles. DESIGN: Prospective cohort
      study. SETTING: University-based tertiary referral center. PATIENT(S): Thirty
      nine consecutive patients <37 years old with PCO or PCOS, who underwent 73 cycles
      of immature oocyte retrieval. INTERVENTION(S): Immature oocyte collection after
      ovarian stimulation with a cumulative dose of 450 IU uFSH or highly purified hMG,
      but without hCG priming. IVM of oocytes followed by ET if endometrium thickness
      >= 6 mm. Embryo vitrification at the cleavage stage. ET in an artificial cycle.
      MAIN OUTCOME MEASURE(S): Implantation rate (IR) and clinical pregnancy rate
      (CPR). RESULT(S): Fresh ET after IVM resulted in an IR of 6.9% (5/72) per ET and
      a CPR of 9.4% (5/53). ET of vitrified-warmed IVM embryos in an artificial cycle
      resulted in significantly better outcomes (IR 21.9% [7/32] and CPR 31.8% [7/22]
      per ET). CONCLUSION(S): A non-hCG-primed IVM system in PCO or PCOS performs
      poorly when embryos are transfered in a fresh cycle. Transfer of vitrified-warmed
      IVM embryos in an artificial cycle leads to significantly improved clinical
      outcomes. These data illustrate that IVM embryos in PCO or PCOS have good
      survival rates and suggest that hCG may be needed to support endometrial
      receptivity in the fresh IVM cycle.

PMID- 21868004
TI  - Programming in vitro fertilization retrievals during working days after a
      gonadotropin-releasing hormone antagonist protocol with estrogen pretreatment:
      does the length of exposure to estradiol impact on controlled ovarian
      hyperstimulation outcomes?
AB  - OBJECTIVE: To verify whether a variable number of days beyond the menses of
      estrogen (E) pretreatment may impact on controlled ovarian hyperstimulation (COH)
      outcomes and birth rate using a GnRH antagonist protocol. DESIGN: Single center,
      prospective, nonrandomized study. SETTING: Nonacademic fertility unit.
      PATIENT(S): A total of 1,080 women, aged 25-38 years, consecutively included
      (1,603 cycles). INTERVENTION(S): Given 4 mg/d E(2) valerate, started 3 days
      before the theoretical date of the next menses up to the first day of stimulation
      (S1). MAIN OUTCOME MEASURE(S): Hormone serum levels, drug exposure, and main IVF
      outcomes. RESULT(S): The cancellation rate was similar in the six similarly sized
      groups according to the number of days with E(2) pretreatment beyond the menses
      (1-8 days). The mean serum E(2) and LH levels at S1 gradually increased along
      with E(2) exposure, whereas the mean serum P level decreased. The mean serum E(2)
      level on the day of hCG administration gradually increased along with E(2)
      exposure. Serum LH level at S1 correlated significantly and positively to the
      length of E(2) exposure and to E(2) level on the day of hCG administration. No
      significant difference was observed for the number of oocytes retrieved and the
      number of embryos obtained. Women exposed the longest to exogenous E(2) tended to
      have higher pregnancy rates (PR). CONCLUSION(S): Extending E(2) pretreatment
      beyond the menses had no deleterious effect on the main COH outcomes and proved
      to be slightly beneficial.

PMID- 21868005
TI  - Variations in the fat mass and obesity-associated (FTO) gene are related to
      glucose levels and higher lipid accumulation product in postmenopausal women from
      southern Brazil.
AB  - OBJECTIVE: To test the association between polymorphisms rs9939609 T>A and
      rs8050136 A>C of the fat mass and obesity-associated (FTO) gene and metabolic and
      cardiovascular variables in postmenopause. DESIGN: Cross-sectional study.
      SETTING: University hospital. PATIENT(S): A total of 135 postmenopausal women
      (mean age 52 +/- 4 years). INTERVENTION(S): Anthropometric measurements and
      collection of blood samples. MAIN OUTCOME MEASURE(S): Blood pressure, metabolic
      variables, and FTO genotype. RESULT(S): The frequency of polymorphism rs9939609
      was 43.7% for the wild TT genotype, 43.0% for TA, and 13.3% for AA. The frequency
      of the rs8050136 polymorphism was 12.6% for the wild AA genotype, 39.3% for AC,
      and 48.1% for CC. The polymorphic AA genotype of the SNP rs9939609 was associated
      with higher glucose levels and lipid accumulation product (LAP) index, whereas
      the wild AA genotype of the SNP rs8050136 was associated with higher LAP.
      CONCLUSION(S): The rs9939609 polymorphism in the FTO gene is related to abnormal
      glucose levels and with LAP, a surrogate marker of diabetes and cardiovascular
      risk in postmenopause. Further studies are needed in different ethnic backgrounds
      to confirm the clinical relevance of these associations.

PMID- 21868007
TI  - Semen quality and fertility in adult long-term survivors of childhood acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: To assess testicular function and its determinants in adult survivors
      of childhood acute lymphoblastic leukemia (ALL) at a median time of 20 years
      after ALL therapy. DESIGN: Prospective investigation. SETTING: University
      hospital. PATIENT(S): Fifty-one male long-term survivors and 56 age-matched
      controls (median age of survivors at ALL diagnosis was 5 years, range: 1 to 15
      years, and at the study 29 years, range: 26 to 38 years). INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Testicular size (mean value of both testicular volumes),
      serum hormone concentrations, semen quality, and number of children fathered
      correlated with ALL therapy. RESULT(S): Survivors treated with 0-10 g/m(2) of
      cyclophosphamide had sperm quality and fertility rates comparable with those of
      controls, but the serum free-testosterone in the survivors treated with
      cyclophosphamide was lower than in controls (median: 213 pmol/L, range: 189-260
      vs. 296 pmol/L, range: 242-338, respectively). Cranial irradiation without
      cyclophosphamide did not affect semen quality, fertility, or testosterone levels.
      None of the survivors of a high cumulative dose of cyclophosphamide (>20 g/m(2))
      and testicular irradiation (10-24 Gy) had fathered a child. Testicular size was
      shown to be better than serum inhibin B in predicting nonazoospermic semen
      samples or fertility. CONCLUSION(S): Treatment of childhood ALL with 0-10 g/m(2)
      of cyclophosphamide and cranial irradiation does not affect fertility or semen
      quality but may impair long-term Leydig cell function.

PMID- 21868006
TI  - Aromatase inhibition for refractory endometriosis-related chronic pelvic pain.
AB  - OBJECTIVE: To evaluate the use of an aromatase inhibitor for the treatment of
      endometriosis-related chronic pelvic pain. DESIGN: Retrospective analysis.
      SETTING: Academic medical center outpatient reproductive endocrinology clinic.
      PATIENT(S): Sixteen patients with endometriosis and chronic pelvic pain who
      previously failed conventional medical and/or surgical therapy. INTERVENTION(S):
      Treatment with the aromatase inhibitor letrozole (2.5 mg/d) plus a gonadotropin
      suppressor (norethindrone acetate, 2.5 mg/d, or a combination oral contraceptive
      [OC]) for an average of 6 months. MAIN OUTCOME MEASURE(S): Pain scores were
      reported at each visit using a visual analogue scale from 0 to 10 (0: no pain,
      10: maximum pain). RESULT(S): Sixteen patients were treated with an aromatase
      inhibitor for 180 +/- 31 days. The median pain score at the start of therapy was
      7, and at the end of therapy it was 1.5. In the nine patients who were evaluated
      after discontinuing therapy, pain scores returned to pretreatment levels. We did
      not find any correlation between the length of treatment and the overall
      improvement in pain score. CONCLUSION(S): Letrozole plus a gonadotropin
      suppressor substantially improved pain symptoms in patients with endometriosis
      refractory to conventional therapies; however, pain recurred after treatment was
      completed.

PMID- 21868008
TI  - Sperm caspase-9 in oligoasthenoteratozoospermic men with and without varicocele.
AB  - OBJECTIVE: To assess sperm caspase-9 activity in infertile
      oligoasthenoteratozoospermic (OAT) men with and without varicocele. DESIGN:
      Prospective. SETTING: Academic setting. PATIENT(S): Eighty men: healthy fertile
      control subjects (n = 20), OAT (n = 25), and OAT associated with left-side
      varicocele (n = 35). INTERVENTION(S): History taking, clinical examination, semen
      analysis,assessment of seminal caspase-9. MAIN OUTCOME MEASURE(S): Semen
      analysis, sperm caspase-9. RESULT(S): Sperm caspase-9 was significantly increased
      in infertile OAT men associated with varicocele compared with OAT men without
      varicocele and healthy fertile control subjects. Sperm casapse-9 activity
      demonstrated significant negative correlation with sperm count, sperm motility,
      sperm velocity, sperm linear velocity, sperm linearity index, and sperm normal
      morphology. CONCLUSION(S): Sperm caspase-9 is exaggerated in infertile OAT cases
      with varicocele compared with infertile OAT cases without varicocele or healthy
      fertile men. Sperm caspase-9 demonstrated significant negative correlation with
      semen variables.

PMID- 21868009
TI  - DC servomechanism parameter identification: a Closed Loop Input Error approach.
AB  - This paper presents a Closed Loop Input Error (CLIE) approach for on-line
      parametric estimation of a continuous-time model of a DC servomechanism
      functioning in closed loop. A standard Proportional Derivative (PD) position
      controller stabilizes the loop without requiring knowledge on the servomechanism
      parameters. The analysis of the identification algorithm takes into account the
      control law employed for closing the loop. The model contains four parameters
      that depend on the servo inertia, viscous, and Coulomb friction as well as on a
      constant disturbance. Lyapunov stability theory permits assessing boundedness of
      the signals associated to the identification algorithm. Experiments on a
      laboratory prototype allows evaluating the performance of the approach.

PMID- 21868010
TI  - Fault tolerant synchronization of chaotic heavy symmetric gyroscope systems
      versus external disturbances via Lyapunov rule-based fuzzy control.
AB  - In this paper, fault tolerant synchronization of chaotic gyroscope systems versus
      external disturbances via Lyapunov rule-based fuzzy control is investigated.
      Taking the general nature of faults in the slave system into account, a new
      synchronization scheme, namely, fault tolerant synchronization, is proposed, by
      which the synchronization can be achieved no matter whether the faults and
      disturbances occur or not. By making use of a slave observer and a Lyapunov rule
      based fuzzy control, fault tolerant synchronization can be achieved. Two
      techniques are considered as control methods: classic Lyapunov-based control and
      Lyapunov rule-based fuzzy control. On the basis of Lyapunov stability theory and
      fuzzy rules, the nonlinear controller and some generic sufficient conditions for
      global asymptotic synchronization are obtained. The fuzzy rules are directly
      constructed subject to a common Lyapunov function such that the error dynamics of
      two identical chaotic motions of symmetric gyros satisfy stability in the
      Lyapunov sense. Two proposed methods are compared. The Lyapunov rule-based fuzzy
      control can compensate for the actuator faults and disturbances occurring in the
      slave system. Numerical simulation results demonstrate the validity and
      feasibility of the proposed method for fault tolerant synchronization.

PMID- 21868012
TI  - Post-registration ICU nurses education: plea for a European curriculum.

PMID- 21868011
TI  - Disaster triage after the Haitian earthquake.
AB  - In the aftermath of the devastating Haitian earthquake, we became the primary
      relief service for a large group of severely injured earthquake victims. Finding
      ourselves virtually isolated with extremely limited facilities and a group of
      critically injured patients whose needs vastly outstripped the available
      resources we employed a disaster triage system to organize their clinical care.
      This report describes the specific injury profile of this group of patients,
      their clinical course, and the management philosophy that we employed. It
      provides useful lessons for similar situations in the future.

PMID- 21868013
TI  - Antiatherogenic effect of pioglitazone on uremic apolipoprotein E knockout mice
      by modulation of the balance of regulatory and effector T cells.
AB  - OBJECTIVE: Uremia markedly accelerates atherogenesis, but the pathogenesis
      remains to be elucidated and effective anti-atherogenic treatments are needed.
      The aim of this study was to investigate the relationship between accelerated
      atherosclerosis (AS) and the balance of regulatory/effector T cells (Treg/Teff)
      in uremic apolipoprotein E knockout (apoE-/-) mice, and the effect of
      pioglitazone on uremic AS and possible mechanisms. METHODS AND RESULTS: Uremia
      was induced surgically in 8-week-old male apoE-/- mice. Two weeks after induction
      of uremia, the mice were randomized to receive pioglitazone (daily oral gavage
      with 20mg/kg) or vehicle. Control apoE-/- mice were sham-operated and received
      vehicle. After 8 weeks' treatment, all mice were sacrificed. The cross-sectional
      area of atherosclerotic lesions at the aortic root was significantly larger and
      plaques were unstable in uremic mice, which was associated with a Treg/Teff
      imbalance (Treg down-regulated/Teff up-regulated) compared with controls. Renal
      function and the percentage of Treg cells in splenocytes were negatively
      correlated in control and uremic mice that received vehicle. Treatment with
      pioglitazone dramatically inhibited AS progression, stabilized plaque and
      modulated the Treg/Teff imbalance (up-regulated Treg/down-regulated Teff) in
      uremic mice, without influencing serum lipid profiles and blood glucose. In
      vitro, oxidized low density lipoprotein induced a Treg/Teff imbalance in
      splenocytes from uremic mice. Pioglitazone modulated the imbalance by
      upregulating Treg cells and downregulating Teff cells. The former was not
      abolished by the peroxisome proliferator-activated receptor (PPAR)gamma
      antagonist GW9662, whereas the latter was completely abolished by GW9662.
      CONCLUSION: Pioglitazone ameliorates accelerated AS in uremic apoE-/- mice,
      probably through PPARgamma-independent and -dependent mechanisms to modulate the
      Treg/Teff imbalance.

PMID- 21868014
TI  - Mechanisms of statin-induced myalgia assessed by physiogenomic associations.
AB  - OBJECTIVE: We investigated genetic variants predictive of muscular side effects
      in patients treated with statins. We utilized a physiogenomic approach to
      prototype a multi-gene panel correlated with statin-induced myalgia. BACKGROUND:
      Statin-induced myalgia occurs in ~10% of lipid clinic outpatients. Its clinical
      manifestation may depend in part upon gene variation from patient to patient.
      METHODS: We genotyped 793 patients (377 with myalgia and 416 without) undergoing
      statin therapy at four U.S. outpatient clinic sites to evaluate 31 candidate
      genes from the literature for their association with statin-induced common
      myalgia. RESULTS: Three previously hypothesized candidate genes were validated:
      COQ2 (rs4693570) encoding para-hydroxybenzoate-polyprenyltransferase, which
      participates in the biosynthesis of coenzyme Q10 (p<0.000041); ATP2B1
      (rs17381194) which encodes a calcium transporting ATPase involved in calcium
      homeostasis (p<0.00079); and DMPK (rs672348) which encodes a protein kinase
      implicated in myotonic dystrophy (p<0.0016). CONCLUSIONS: The candidate genes
      COQ2, ATP2B1, and DMPK, representing pathways involved in myocellular energy
      transfer, calcium homeostasis, and myotonic dystonia, respectively, were
      validated as markers for the common myalgia observed in patients receiving statin
      therapy. The three genes integrated into a physiogenomic predictive system could
      be relevant to myalgia diagnosis and prognosis in clinical practice.

PMID- 21868015
TI  - Different stages of intraplaque hemorrhage are associated with different plaque
      phenotypes: a large histopathological study in 794 carotid and 276 femoral
      endarterectomy specimens.
AB  - BACKGROUND AND PURPOSE: Intraplaque hemorrhage (IPH) is an important determinant
      of progression and destabilization of atherosclerotic plaque. We recently
      demonstrated that IPH is an independent predictor of cardiovascular events. IPH
      has become more clinically relevant since magnetic resonance imaging (MRI)
      technique is able to visualize IPH in vivo. Different stages of IPH have been
      described. However, etiology of the different stages is not known and it is
      unclear if these detected different stages are all associated with the vulnerable
      plaque phenotype. METHODS AND RESULTS: 1070 patients who underwent a carotid
      (n=794) or femoral (n=276) endarterectomy were included. Histopathological
      presence of IPH was determined and divided into 3 types: recent, organized and
      amorphous IPH. Carotid IPH was observed in 644/794 (81%) plaques, divided into 14
      (2%) recent, 70 (11%) organized and 560 (87%) amorphous. Femoral IPH was observed
      in 175/276 (63%) plaques, divided into 2 (1%) recent, 89 (51%) organized and 84
      amorphous (48%). Overall presence of carotid IPH was associated with a large
      lipid core, no or minor staining of smooth muscle cells, no or minor
      calcification and high microvessel density. Overall presence of femoral IPH was
      associated with moderate to heavy staining of macrophages. Plaques with organized
      IPHs revealed more macrophages, a larger lipid core, less smooth muscle cells,
      less calcification and higher microvessel density than plaques with amorphous
      IPHs. CONCLUSIONS: IPH is a significant characteristic of carotid and femoral
      atherosclerotic plaque and can be classified into different types. Organized IPH
      is associated with unstable and amorphous IPH with stable plaque characteristics.

PMID- 21868016
TI  - Reduced penetrance of autosomal dominant hypercholesterolemia in a high
      percentage of families: importance of genetic testing in the entire family.
AB  - BACKGROUND: Autosomal dominant hypercholesterolemias (ADHs) are characterised by
      increased plasma levels of total and LDL cholesterol, predisposing to premature
      atherosclerosis. ADHs comprise several diseases with undistinguishable phenotype,
      caused by mutations in different genes: LDLR, APOB and PCSK9. Genetic studies are
      usually performed in patients with altered cholesterol levels. However, some
      persons carrying pathogenic mutations are normocholesterolemic and there are no
      further studies about this subject. We have studied the frequency of families and
      individuals carrying ADH mutations who do not present the disease in Spanish
      population. METHODS: We have analysed genes known to cause ADH by direct
      sequencing in 24 ADH families (215 members). Functional effect of some LDLR gene
      mutations was assessed by transfecting cultured cells with plasmids. RESULTS: Six
      families with mutations presented 7 mutation carriers who did not show ADH
      phenotype: 30% of ADH families presented normocholesterolemic individuals, and 7%
      of carriers of pathogenic mutations did not show ADH phenotype. We have analysed
      the effect of some of these mutations and they are responsible for impaired LDL
      receptor function. We have excluded mutations in APOB and PCSK9 genes that could
      reduce LDLc levels. CONCLUSIONS: An important percentage of ADH families
      presented individuals who do not show an ADH phenotype, but who are able to
      transmit the pathogenic mutation to their offspring. Genetic study of all
      subjects in ADH families should be performed in order to identify
      normocholesterolemic carriers that allow the detection of mutations in their
      descendants and the prevention of the disease consequences.

PMID- 21868017
TI  - Relation of cholesterol and lipoprotein parameters with carotid artery plaque
      characteristics: the Atherosclerosis Risk in Communities (ARIC) carotid MRI
      study.
AB  - OBJECTIVE: There is a paucity of data regarding relations of apolipoproteins
      (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle
      measures (low-density lipoprotein particle concentration [LDLp] and high-density
      lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures
      (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein
      cholesterol [non-HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with
      atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence
      as a marker of high-risk plaques. METHODS: Carotid artery magnetic resonance
      imaging was performed in 1670 Atherosclerosis Risk in Communities study
      participants. Vessel wall and lipid cores were measured; normalized wall index
      (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity)
      were calculated; and lipid cores were detected in vessels with >= 1.5mm
      thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and
      HDLp were measured. RESULTS: Measures of plaque burden (carotid wall volume, wall
      thickness, and NWI) were positively associated with atherogenic cholesterol and
      lipoproteins (p < 0.05 for total cholesterol, LDL-C, non-HDL-C, ApoB, and LDLp),
      but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with
      total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of
      atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually
      associated with detection of a lipid-rich core, their ratios (total
      cholesterol/HDL-C, non-HDL-C/HDL-C, and LDLp/HDLp) were associated with lipid
      rich core presence (p <= 0.05). CONCLUSION: Extent of carotid atherosclerosis is
      associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti
      atherogenic cholesterol or particle ratios were associated with presence of a
      detectable lipid-rich core.

PMID- 21868018
TI  - Genetic variants of the monocyte chemoattractant protein-1 gene and its receptor
      CCR2 and risk of coronary artery disease: a meta-analysis.
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine
      (C-C motif) receptor 2 (CCR2) are implicated in promoting atherosclerosis. Many
      studies have searched the association between variants of the MCP-1 gene or CCR2
      gene and risk of coronary artery disease (CAD), but the results are inconsistent.
      METHODS: We conducted a meta-analysis of 20 publications including 24 studies on
      2 genetic variants [A-2518G in the MCP-1 and V64I in the CCR2] published before
      January 2011, including a total of 9844 patients with CAD and 11,821 controls.
      Publication bias and heterogeneity among studies were explored. RESULTS: In a
      combined analysis, the pooled OR for CAD of the -2518G allele was 1.42 (95%CI:
      1.06-1.92) compared to wild-type A allele under a recessive model in Caucasian
      group, but there is an indication of publication bias and heterogeneity among the
      9 studies. When the analyses were restricted to 2 large studies (n>=500 cases),
      the pooled OR was 1.08 (95%CI: 0.85-1.37). Our analyses detected a possibility of
      publication bias with an overestimate of the true association by smaller studies.
      A meta-analysis of studies on the CCR2 V64I variant showed no significant
      association with CAD, the pooled OR of 64I was 1.27 (95%CI: 0.81-1.99) in
      recessive model and 1.06 (95%CI: 0.95-1.19) in dominant model, respectively.
      CONCLUSIONS: The results indicate that MCP-1-2518G allele had probably increased
      risk of CAD in Caucasian but this is likely to be due to publication bias and
      insufficient sample size. The CCR2 V64I has not been found any association with
      CAD.

PMID- 21868019
TI  - Enantiomeric resolution of (+/-)-licarin A by high-performance liquid
      chromatography using a chiral stationary phase.
AB  - (+/-)-Licarin A (1), a neolignan obtained by the oxidative coupling reaction of
      isoeugenol, had in this study its enantiomers resolved. A novel, quick and
      efficient enantiomeric resolution of 1 was directly performed by chiral high
      performance liquid chromatography (HPLC-PDA) protocol (CHIRALPACK((r)) AD column;
      9:1 (v/v) n-hexane:2-propanol; 1.0 mL/min). This method provided a chromatogram
      profile with a well-resolved peak separation. After isolation of each enantiomer
      with ee>99.9%, they were analysed in a polarimeter. Compound 2, which showed a
      retention time (t(r)) of 12.13 min, was the (+)-enantiomer and compound 3
      (t(r)=18.90 min) was the (-)-enantiomer.

PMID- 21868020
TI  - High-throughput protein precipitation and hydrophobic interaction chromatography:
      salt effects and thermodynamic interrelation.
AB  - Salt-induced protein precipitation and hydrophobic interaction chromatography
      (HIC) are two widely used methods for protein purification. In this study, salt
      effects in protein precipitation and HIC were investigated for a broad
      combination of proteins, salts and HIC resins. Interrelation between the critical
      thermodynamic salting out parameters in both techniques was equally investigated.
      Protein precipitation data were obtained by a high-throughput technique employing
      96-well microtitre plates and robotic liquid handling technology. For the same
      protein-salt combinations, isocratic HIC experiments were performed using two or
      three different commercially available stationary phases-Phenyl Sepharose low
      sub, Butyl Sepharose and Resource Phenyl. In general, similar salt effects and
      deviations from the lyotropic series were observed in both separation methods,
      for example, the reverse Hofmeister effect reported for lysozyme below its
      isoelectric point and at low salt concentrations. The salting out constant could
      be expressed in terms of the preferential interaction parameter in protein
      precipitation, showing that the former is, in effect, the net result of
      preferential interaction of a protein with water molecules and salt ions in its
      vicinity. However, no general quantitative interrelation was found between
      salting out parameters or the number of released water molecules in protein
      precipitation and HIC. In other words, protein solubility and HIC retention
      factor could not be quantitatively interrelated, although for some proteins,
      regular trends were observed across the different resins and salt types.

PMID- 21868021
TI  - Analytical method for the simultaneous determination of polyfunctional amines
      used as monomers in the manufacture of food packaging materials.
AB  - This paper describes the development of a multi-analyte method for the
      determination of polyfunctional amines commonly used as monomers in the
      manufacture of food contact materials. Amines were analyzed by high-performance
      liquid chromatography with diode-array detection (HPLC-DAD) after derivatization
      with dansyl chloride. The chromatographic analysis and the derivatization
      conditions were optimized. The proposed method was validated in terms of
      linearity, limits of detection and repeatabilities. The method showed an
      excellent sensitivity (LOD<=0.05 MUg/mL) and appropriate repeatabilites (RSD
      (n=7)<=5%)). LC-MS/MS was used as a confirmatory technique. The stability of the
      amines in five food simulants (distilled water, 3% acetic acid, 10% ethanol, 50%
      ethanol and olive oil) under the most common testing conditions (10 days at 40 
      degrees C) was also studied. Results showed that amines had an acceptable
      stability in aqueous simulants but in the olive oil a loss of 100% was observed
      for all analytes.

PMID- 21868022
TI  - Separation and recycling of nanoparticles using cloud point extraction with non
      ionic surfactant mixtures.
AB  - A viable cost-effective approach employing mixtures of non-ionic surfactants
      Triton X-114/Triton X-100 (TX-114/TX-100), and subsequent cloud point extraction
      (CPE), has been utilized to concentrate and recycle inorganic nanoparticles (NPs)
      in aqueous media. Gold Au- and palladium Pd-NPs have been pre-synthesized in
      aqueous phases and stabilized by sodium 2-mercaptoethanesulfonate (MES) ligands,
      then dispersed in aqueous non-ionic surfactant mixtures. Heating the NP-micellar
      systems induced cloud point phase separations, resulting in concentration of the
      NPs in lower phases after the transition. For the Au-NPs UV/vis absorption has
      been used to quantify the recovery and recycle efficiency after five repeated CPE
      cycles. Transmission electron microscopy (TEM) was used to investigate NP size,
      shape, and stability. The results showed that NPs are preserved after the
      recovery processes, but highlight a potential limitation, in that further
      particle growth can occur in the condensed phases.

PMID- 21868023
TI  - Addition of silica nanoparticles to tailor the mechanical properties of
      nanofibrillated cellulose thin films.
AB  - Over the last decade, the use of nanocellulose in advanced technological
      applications has been promoted both due the excellent properties of this material
      in combination with its renewability. In this study, multilayered thin films
      composed of nanofibrillated cellulose (NFC), polyvinyl amine (PVAm) and silica
      nanoparticles were fabricated on polydimethylsiloxane (PDMS) using a layer-by
      layer adsorption technique. The multilayer build-up was followed in situ by
      quartz crystal microbalance with dissipation, which indicated that the PVAm
      SiO(2)-PVAm-NFC system adsorbs twice as much wet mass material compared to the
      PVAm-NFC system for the same number of bilayers. This is accompanied with a
      higher viscoelasticity for the PVAm-SiO(2)-PVAm-NFC system. Ellipsometry
      indicated a dry-state thickness of 2.2 and 3.4 nm per bilayer for the PVAm-NFC
      system and the PVAm-SiO(2)-PVAm-NFC system, respectively. Atomic force microscopy
      height images indicate that in both systems, a porous network structure is
      achieved. Young's modulus of these thin films was determined by the Strain
      Induced Elastic Buckling Instability for Mechanical Measurements (SIEBIMM)
      technique. The Young's modulus of the PVAm/NFC films was doubled, from 1 to 2
      GPa, upon incorporation of silica nanoparticles in the films. The introduction of
      the silica nanoparticles lowered the refractive index of the films, most probably
      due to an increased porosity of the films.

PMID- 21868024
TI  - Adsorption of BTX (benzene, toluene, o-xylene, and p-xylene) from aqueous
      solutions by modified periodic mesoporous organosilica.
AB  - The capacity of a periodic mesoporous organosilica (PMO) to adsorb the aromatic
      compounds benzene, toluene, o-, and p-xylenes (BTX), which are usually present in
      produced waters, was investigated under both column and batch processes. The PMO
      was synthesized by condensation of 1,4 bis(triethoxisilyl)benzene (BTEB) under
      acidic conditions by using structure-directing agent (SDA) Pluronic P123 in the
      presence of KCl. Thermogravimetric analysis showed that the presence of the
      surfactant decreases the thermal stability of the PMO. The small-angle X-ray
      diffraction pattern, as well as the nitrogen adsorption/desorption isotherm
      measurements, revealed that the synthesized material has a crystalline structure,
      with hexagonally-ordered cylindrical mesopores. The adsorption kinetics study
      indicated an adsorption equilibrium time of 50 min and also showed that the data
      best fitted the pseudo-first order kinetic model. The intraparticle diffusion
      model was also tested and pointed to the occurrence of such process in all cases.
      Both Langmuir and Temkin models best represented the adsorption isotherms of
      toluene; Langmuir and Redlich-Peterson models best represented the data obtained
      for the other compounds. Adsorption capacity decreases in the order benzene>o
      xylene>p-xylene>toluene. Satisfactory results were observed in the application of
      the synthesized PMO for the removal of BTX from aqueous solution.

PMID- 21868025
TI  - Effects of electrolyte concentration and counterion valence on the
      microstructural flow regimes in dilute cetyltrimethylammonium tosylate micellar
      solutions.
AB  - The shear thickening behavior and the transition to shear thinning are examined
      in dilute cetyltrimethylammonium tosylate (CTAT) micellar solutions as a function
      of surfactant concentration and ionic strength using electrolytes with different
      counterion valence. Newtonian behavior at low shear rates, followed by shear
      thickening and shear thinning at higher shear rates, are observed at low and
      intermediate surfactant and electrolyte concentrations. Shear thickening
      diminishes with increasing surfactant concentration and ionic strength. At higher
      surfactant or electrolyte concentration, only a Newtonian region followed by
      shear thinning is detected. A generalized flow diagram indicates two controlling
      regimes: one in which electrostatic screening dominates and induces micellar
      growth, and another, at higher electrolyte and surfactant concentrations, where
      chemical equilibrium among electrolyte and surfactant counterions controls the
      rheological behavior by modifying micellar breaking and reforming. Analysis of
      the shear thickening behavior reveals that not only a critical shear rate is
      required for shear thickening, but also a critical deformation, which appears to
      be unique for all systems examined, within experimental error. Moreover, a
      superposition of the critical shear rate for shear thickening with surfactant and
      electrolyte concentration is reported.

PMID- 21868027
TI  - Inadvertent interchange of electrocardiogram limb lead connections: analysis of
      predicted consequences part II: double interconnection errors.
AB  - Limb lead connection errors are known to be very common in clinical practice. The
      consequences of all possible single limb lead interconnection errors were
      analyzed in an earlier publication (J Electrocardiology 2008;41:84-90). With a
      single limb lead interconnection error, 6 combinations of limb lead connections
      are possible. Two of these combinations give rise to records in which the limb
      lead morphology is uninterpretable. Such records show a "flat line" in lead II or
      III. Three of the errors give rise to records that are fully interpretable once
      the specific interconnection error has been identified (although one of the
      errors cannot reliably be recognized in the absence of a previous record for
      comparison). One of the errors produces no change in the electrocardiogram
      recording. In all cases, the precordial leads are interpretable, although there
      are very minor changes in the voltages. This communication predicts the changes
      in limb lead appearances consequent upon all possible double limb lead
      interchanges and illustrates these with records electively taken with such double
      interconnection errors. There are only 3 possible double limb lead
      interconnection errors. In 2 of the possible combinations, interpretation of the
      limb leads is impossible, and each of these errors gives rise to a flat line in
      lead I. In the third combination, the record is fully interpretable once the
      abnormality has been identified. In all 3 types, the precordial leads are
      interpretable, although there are very minor changes in the voltages.

PMID- 21868026
TI  - Modulation of cytokine mRNA expression in pharyngeal epithelial samples obtained
      from cattle infected with foot-and-mouth disease virus.
AB  - A novel technique of endoscopical collection of small tissue samples was used to
      obtain sequential tissue samples from the dorsal soft palate (DSP) of individual
      cattle infected with foot-and-mouth disease virus (FMDV) at different phases of
      the infection. Levels of mRNA encoding interferon (IFN)-alpha and IFN-beta as
      well as tumour necrosis factor (TNF)-alpha were measured in these samples by
      quantitative reverse transcriptase polymerase chain reaction. Expression of IFN
      beta mRNA was significantly down-regulated in the biopsy samples harvested during
      the acute phase of infection, while there was no statistically significant effect
      on the expression of IFN-alpha mRNA compared with baseline levels. In contrast,
      the mRNA encoding TNF-alpha was significantly up-regulated in samples collected
      during both acute and late (>28 days post infection) phases of infection. There
      were also significantly higher levels of TNF-alpha mRNA expressed in samples
      derived from animals that were identified subsequently as persistently infected
      FMDV-carriers. It was concluded that there was a significant difference in the
      host-response in the DSP of calves that were identified as persistently infected,
      subclinical carriers of FMDV.

PMID- 21868028
TI  - Deaths in preterm infants: changing pathology over 2 decades.
AB  - OBJECTIVE: To establish how cause of death for live-born preterm infants (24-31
      weeks gestation) has changed in a single large UK population over 2 decades.
      STUDY DESIGN: This was an interrogation of a population-based survey of >680, 000
      live births (between 1988 and 2008) for deaths in the first postnatal year. We
      collected cause of death grouped into major etiologies: respiratory, infection,
      malformation, necrotizing enterocolitis (NEC), and other. Data were analyzed in
      three 7-year epochs and 2 gestational groups (<27 and 28-31 weeks). Numbers,
      rates per 1000 live births, and proportional contributions to each epoch were
      analyzed. RESULTS: A total of 1504 deaths occurred. The infants who died had a
      median gestational age of 26 weeks (IQR, 25-28 weeks) and a median birth weight
      of 880 g (IQR, 700-1170 g). The number of deaths decreased with each later epoch
      (from 671 to 473 and then to 360), as did the proportion of deaths from
      respiratory causes (64% to 62% and then to 49%). The proportion of deaths
      occurring after 40 weeks postmenstrual age remained stable across the 3 epochs
      (8.8%, 8%, and 8%). Deaths from infection and NEC increased with time (from 11%
      to 13% and then to 21%), as did median time to death (from 2.7 to 3.8 days).
      CONCLUSION: Infection and NEC are increasingly prevalent causes of death in
      preterm infants.

PMID- 21868029
TI  - Performance of HIV-1 DNA or HIV-1 RNA tests for early diagnosis of perinatal HIV
      1 infection during anti-retroviral prophylaxis.
AB  - OBJECTIVE: To compare performance of testing for human immunodeficiency virus
      (HIV)-1 DNA and HIV-1 RNA for diagnosis of HIV-1 infection in infants receiving
      preventive antiretroviral therapy. STUDY DESIGN: This substudy of the French
      multicenter prospective cohort of neonates born to HIV-infected mothers, included
      1567 infants tested for HIV with polymerase chain reaction (PCR) in a single
      laboratory, receiving post-natal prophylaxis, not breastfed, and having
      simultaneous HIV-1 DNA and RNA results before 45 days. The performance of PCR was
      assessed in reference to the 6-month HIV-1 RNA result. RESULTS: Specificity of
      both HIV-1 RNA and HIV-1 DNA PCR was 100% at all ages (except 99.8% for DNA at
      birth); sensitivity was 58% (RNA) and 55% (DNA) at birth, and 89% at 1 month,
      100% at 3 months for both, and 100% at 6 months (DNA). Concordance between HIV-1
      DNA and RNA results was 0.78 and 0.81 (Kappa) at birth and 1 month and 100% at 3
      and 6 months. Type of maternal and neonatal prophylaxis had no effect on
      sensitivity, but influenced viral load. CONCLUSION: The performances of testing
      for HIV-1 DNA and RNA were similar with 100% sensitivity at 3 months. At 1 month
      during prophylaxis, 11% of infected children had negative PCR results.

PMID- 21868030
TI  - Psychiatric disorders in youth with medically unexplained chest pain versus
      innocent heart murmur.
AB  - OBJECTIVE: To examine the prevalence of Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition psychiatric disorders in youth with chest pain
      compared with a control sample with innocent heart murmur. STUDY DESIGN: We
      assessed youth ages 8 to 17 years who were examined in cardiology settings for
      medically unexplained chest pain (n=100) or innocent heart murmur (n=80). We
      conducted semi-structured interviews and assessed medical history, quality of
      life, and disability. RESULTS: Youth with chest pain had a higher prevalence of
      psychiatric disorders compared with youth with murmur (74% versus 47%,
      chi(2)=13.3; P<.001). Anxiety disorders predominated, although major depression
      was also more common in the chest pain group (9% versus 0%; Fisher exact tests;
      P<.01). Onset of psychiatric disorders generally preceded chest pain. Patterns
      were similar for boys and girls and for children and adolescents. Chest pain was
      associated with poorer quality of life and with pain-related disability for youth
      with co-morbid psychiatric disorder. CONCLUSIONS: In childhood and adolescence,
      medically unexplained chest pain is associated with a high prevalence of
      psychiatric disorders. Systematic mental health screening may improve detection
      and enhance treatment of these patients.

PMID- 21868031
TI  - Protracted bacterial bronchitis in young children: association with airway
      malacia.
AB  - OBJECTIVE: To examine associated findings and clinical outcome in young children
      with prolonged cough, wheeze, and/or noisy breathing in whom high colony counts
      of potentially pathogenic bacteria were cultured from bronchoalveolar lavage
      (BAL) during diagnostic flexible fiberoptic bronchoscopy. STUDY DESIGN: This was
      a retrospective review of all medical records of children from infancy to 60
      months of age seen in our specialty clinic from 1999 to 2009 with protracted
      cough, wheeze, and/or noisy breathing in whom BAL found >= 10(4) colony forming
      units per milliliter of potentially pathogenic bacteria. Children with other
      major diagnoses were excluded. RESULTS: With quantitative culture from BAL, >=
      10(4) colony forming units per milliliter of Streptococcus pneumoniae,
      Haemophilus influenza, or Moraxella catarrhalis, separately or in combination,
      were found in 70 children. Neutrophilia was present in 87% of BALs.
      Tracheomalacia, bronchomalacia, or both was present in 52 children (74%).
      Symptoms were eliminated with antibiotics in all 61 children with follow-up data.
      Relapse and subsequent successful re-treatment occurred in 43 children.
      CONCLUSIONS: High colony counts of potentially pathogenic bacteria associated
      with neutrophilia in the BAL identifies protracted bacterial bronchitis. The
      predominance of airway malacia in these patients suggests an etiologic role for
      those airway anomalies. The potential for chronic airway damage from protracted
      bacterial bronchitis warrants further investigation.

PMID- 21868032
TI  - Bed sharing and the risk of sudden infant death syndrome: can we resolve the
      debate?
AB  - OBJECTIVE: To conduct a meta-analysis on the relationship between bed sharing and
      sudden infant death syndrome (SIDS) risk. STUDY DESIGN: Data from PubMed and
      Medline were searched for studies published after Jan 1, 1970. The search
      strategy included articles with the terms "sudden infant death syndrome," "sudden
      unexpected death," and "cot death" with "bed sharing" or "co-sleeping." To
      further specify the potential risk of bed sharing and SIDS, subgroup analyses
      were performed. RESULTS: Eleven studies met inclusion criteria and were included
      in the final meta-analysis. The combined OR for SIDS in all bed sharing versus
      non-bed sharing infants was 2.89 (95% CI, 1.99-4.18). The risk was highest for
      infants of smoking mothers (OR, 6.27; 95% CI, 3.94-9.99), and infants <12 weeks
      old (OR, 10.37; 95% CI, 4.44-24.21). CONCLUSIONS: Bed sharing is a risk factor
      for SIDS and is especially enhanced in smoking parents and in very young infants.

PMID- 21868033
TI  - Clinical factors associated with pediatric autoimmune neuropsychiatric disorders
      associated with streptococcal infections.
AB  - OBJECTIVE: To explore associated clinical factors in children with pediatric
      autoimmune neuropsychiatric disorders associated with streptococcal infections
      (PANDAS). STUDY DESIGN: Children with tics, obsessive-compulsive disorder, or
      both (n=109) were examined with personal and family history, diagnostic
      interview, physical examination, medical record review, and measurement of
      baseline levels of streptococcal antibodies. RESULTS: Significant group
      differences were found on several variables, such that children in whom PANDAS
      (versus without PANDAS) were more likely to have had dramatic onset, definite
      remissions, remission of neuropsychiatric symptoms during antibiotic therapy, a
      history of tonsillectomies/adenoidectomies, evidence of group A streptococcal
      infection, and clumsiness. CONCLUSION: The identification of clinical features
      associated with PANDAS should assist in delineating risks for this subtype of
      obsessive-compulsive disorder/tics.

PMID- 21868034
TI  - Diffuse linear and whorled nevoid hypermelanosis in a newborn.

PMID- 21868035
TI  - Transition from pediatric to adult healthcare services for young adults with
      chronic illnesses: the special case of human immunodeficiency virus infection.

PMID- 21868036
TI  - Lower airway nitric oxide is increased in children with sickle cell disease.
AB  - OBJECTIVES: To determine alveolar and airways nitric oxide (NO) levels in
      children with sickle cell disease (SCD). STUDY DESIGN: Multiple flows fractional
      exhaled NO (FE(NO)), bronchial NO flux (J'aw(NO)), and alveolar NO concentration
      (Ca(NO)) were determined prospectively in 16 non-atopic children with SCD in a
      tertiary ambulatory clinic and compared with those in 10 children with primary
      ciliary dyskinesia and 22 healthy control subjects. Differences in FE(NO),
      J'aw(NO), and Ca(NO) were compared with mixed model analysis and Mann-Whitney
      tests. RESULTS: Children with SCD had reference range FE(NO) at 50 mL/sec, but
      FE(NO) was elevated across all flows compared with healthy control subjects (mean
      difference=2.10+/-0.91 parts per billion, P=.03). Subjects with SCD had increased
      J'aw(NO) (1177+/-533 picoliters per second versus 833+/-343 picolitres per
      second, P=.03), and Ca(NO) was no different from control subjects. In contrast,
      children with primary ciliary dyskinesia had decreased FE(NO) (mean
      difference=3.36+/-1.24 parts per billion, P<.01) and J'aw(NO) (507+/-259
      picoliters per second versus 833+/-343 picoliters per second, P<.01).
      CONCLUSIONS: Lower airways NO is increased in children with SCD. Elevation of
      J'aw(NO) may represent dysregulation of NO metabolism or subclinical airways
      inflammation.

PMID- 21868037
TI  - Development of hypertension in adolescents with pre-hypertension.
AB  - OBJECTIVE: To evaluate the risk for developing incident hypertension (HTN) in
      adolescents with pre-hypertension. STUDY DESIGN: A secondary analysis of students
      participating in multiple school-based blood pressure (BP) screens from 2000 to
      2007 was completed. At each screen, height, weight, and 2 to 4 BPs were measured
      on as many as 3 occasions when BP remained >= 95th percentile. Students with
      confirmed HTN at their initial screen were excluded, and incident HTN was defined
      as having a BP >= 95th percentile at all 3 visits of a later screen. Incidence
      rates (IR) and hazard ratios (HR) were calculated by using Cox Proportional
      models. RESULTS: Of 1006 students, HTN developed in 11 (IR 0.5%/year) in a mean
      of 2.1 years of observation. IRs were higher in "at-risk" students (pre
      hypertensive or hypertensive with follow-up BP <95th percentile), 1.4%/year (HR,
      4.89; 1.48-16.19) and students with a BP >= 90th percentile at 3 baseline visits,
      6.6%/year HR 24.33 (5.68-104.29)]. Although not significant, students with pre
      hypertension by the 2004 Task Force definition also had an increased IR of
      1.1%/year (HR, 2.98; 0.77-11.56)]. CONCLUSION: Elevated BP increases the risk for
      the development of HTN during adolescence. Effective strategies for preventing
      HTN in at-risk adolescents are needed.

PMID- 21868039
TI  - Dopaminergic dysregulation syndrome in Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative condition which
      requires gradually increasing doses of dopaminergic substances for adequate motor
      control. Some vulnerable patients increase their doses beyond those required for
      motor control. This may result in a pattern of compulsive drug taking which may
      be associated with typical behavioural changes which define dopaminergic
      dysregulation syndrome (DDS). This is frequently associated with impulse control
      disorders and a specific behavioural abnormality involving prolonged repetitive
      tasks, called punding. The pathophysiology of DDS likely involves a number of
      factors, including genetic and personality related risk factors, habit formation
      resulting from unpleasant OFF symptoms, fronto-striatal dysfunction and a
      sensitisation process due to repeated dopaminergic stimulation. Management
      includes attempts to reduce the dopaminergic dose; specific treatment options are
      currently unknown. Early detection and prevention are therefore essential.

PMID- 21868038
TI  - Adipocytokines and ischemic stroke: differential associations between stroke
      subtypes.
AB  - OBJECTIVE: Experimental studies have indicated that adipocytokines are associated
      with vascular diseases with regard to the pathology of atherosclerotic plaque. We
      hypothesized that the strength of the associations between adipocytokines and
      stroke would differ between ischemic stroke subtypes. METHODS: A total of 96
      acute ischemic stroke patients (within 5 days from onset) and 48 non-stroke
      subjects were analyzed in this study. Stroke patients were comprised of 26
      strokes due to large artery atherosclerosis (LAA) and 72 non-LAA strokes. Venous
      blood from all participants was drawn after an overnight fast, and serum levels
      of leptin, adiponectin and resistin were measured by multiple sandwich
      immunoassay techniques. RESULTS: Compared with non-LAA strokes, patients with LAA
      strokes had lower levels of serum adiponectin (6.4 +/- 3.1 vs. 8.5 +/- 3.9
      MUg/mL; P=0.04), and a higher level of leptin-to-adiponectin ratio (L:A ratio;
      1.6 +/- 1.4 vs. 0.9 +/- 0.9; P<0.01). Multinomial logistic regression analyses
      showed that, although none of the adipocytokines was associated with non-LAA
      strokes, lower adiponectin (adjusted OR, 0.79 per 1-MUg/mL increase; 95% CI, 0.64
      0.98), higher leptin (aOR, 1.12 per 1-ng/mL increase; 95% CI, 1.004-1.25) and
      higher L:A ratio (aOR, 2.93 per 1-quartile increase; 95% CI, 1.39-6.15) showed
      significant associations with increased odds of having LAA stroke, compared to
      non-stroke subjects. CONCLUSION: From our study, we documented that leptin and
      adiponectin had differential association patterns with ischemic stroke according
      to the stroke subtype. Careful consideration of the heterogeneity of stroke
      subtypes would be warranted in studying the utility of biomarkers including
      adipocytokines.

PMID- 21868040
TI  - Superficial siderosis due to dural defect with thoracic spinal cord herniation.
AB  - Superficial siderosis (SS) of the central nervous system is a rare disorder
      caused by chronic or recurrent hemorrhages into the subarachnoid space with
      hemosiderin and ferritin deposition, which leads to neuronal damage. The source
      of bleeding remains unknown in 50% of cases. Recently, attention has been focused
      on fluid-filled collection in the spinal canal, suggesting the presence of a
      dural defect which may be the bleeding point. We present a patient with SS and
      spinal extradural fluid collection due to midthoracic dural defect with spinal
      cord herniation. The reduction of the spinal cord herniation and the repair of
      the dural defect resulted in the disappearance of the fluid collection and
      cerebrospinal fluid abnormalities. The case here reported is, to our knowledge,
      the first case of spinal cord herniation presenting with SS and confirms the key
      role played by dural lacerations in the pathogenesis of both SS and spinal cord
      herniation. The search for dural lacerations should be one of the primary aims in
      patients with SS.

PMID- 21868041
TI  - Effect of aneurysm on the mechanical dissection properties of the human ascending
      thoracic aorta.
AB  - OBJECTIVES: The acute dissection of an ascending thoracic aortic aneurysm (ATAA)
      represents a devastating separation of elastic layers occurring when the
      hemodynamic loads on the diseased wall exceed the adhesive strength between
      layers. At present, the mechanics underlying aortic dissection are largely
      unclear, and the biomechanical delamination properties of the aneurysmal aorta
      are not defined. Individuals with bicuspid aortic valve (BAV) are particularly
      predisposed to ascending aortic aneurysm formation, with a marked risk of aortic
      dissection. The purpose of this study was to evaluate and compare the dissection
      properties of nonaneurysmal and aneurysmal human ascending thoracic aorta from
      patients with BAV morphology or normal tricuspid aortic valve (TAV) morphology
      using biomechanical delamination testing. METHODS: The influence on the
      delamination strength (S(d)) of the aorta associated with BAV was compared with
      that in patients with TAV. After complete delamination of ATAA tissue samples,
      tensile tests were performed on each delaminated half for comparison of their
      tensile strengths. RESULTS: The results showed that the aneurysmal aortas with
      BAV and TAV have lower S(d) than nonaneurysmal aortas and that ATAA with BAV has
      a lower S(d) than that with TAV. We have found a significant difference in S(d)
      between longitudinal and circumferential directions of the nondiseased aorta,
      suggesting anisotropic dissection properties. CONCLUSIONS: The tensile testing
      results suggest that the weaker intimal half of the aortic wall might fail before
      the outer adventitial half. Scanning electron microscope analyses suggest
      different failure modalities of dissection between the two morphologies, and the
      lower S(d) in ATAAs appears to be associated with a disorganized microstructure.
      BAV ATAAs have a lower S(d) than TAV ATAAs, suggesting a greater propensity for
      aortic dissection.

PMID- 21868042
TI  - Single-incision video-assisted thoracoscopic lobectomy: initial results.

PMID- 21868043
TI  - Short- and long-term outcomes in patients undergoing valve surgery with end-stage
      renal failure receiving chronic hemodialysis.
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of chronic
      preoperative hemodialysis for end-stage renal failure in patients undergoing
      valve surgery. METHODS: A retrospective review of patients undergoing primary
      valve with or without coronary artery bypass surgery from 1996 to 2008 at a US
      academic center was performed. The patients were divided into two groups: group 1
      underwent valve surgery without preoperative dialysis (n = 5084) and group 2
      underwent valve surgery with preoperative dialysis (n = 224). The outcomes were
      evaluated using multivariate regression analysis, and long-term survival was
      assessed with Kaplan-Meier plots. RESULTS: The patients in group 2 were younger
      (P < .001), were more likely women (P = .04), and presented with New York Heart
      Association class III-IV (P < .001). The ejection fraction was similar between
      the two groups (P = .36). The adjusted perioperative morbidity was similar
      between the two groups for stroke (P = .79) and myocardial infarction (P = .68).
      Resource use (postoperative length of stay) was greater in group 2 (P < .001), as
      was in-hospital mortality (group 1, 263/5084 [5.2%] vs group 2, 41/224 [18.3%]; P
      < .001). The 1-, 5-, and 10-year survival was less in group 2 (P < .001); the
      median survival was 12 or more years in group 1 and 1.8 years in group 2.
      Preoperative end-state renal disease, among others, show a trend as an
      independent predictor for short-term mortality and was a significant predictor
      for long-term mortality. CONCLUSIONS: In this large cohort of patients,
      preoperative dialysis conferred a high risk of perioperative morbidity and
      mortality and poor long-term survival after valve surgery. Risk stratification
      and future research efforts should focus on more precise identification of the
      benefits of valve surgery in this high-risk patient population.

PMID- 21868044
TI  - Impacts of maintenance dredged material disposal on macrobenthic structure and
      secondary productivity.
AB  - The results of a monitoring programme to assess the spatial impacts associated
      with ongoing dredged material disposal activity at a dispersive, coastal disposal
      site (southwest UK) are described. Benthic impacts were assessed using benthic
      community structure and secondary productivity estimates. Analyses of univariate
      indices (including secondary production) and multivariate community structure
      revealed differences between stations inside and those outside the disposal site
      were minimal. Generally, stations within and outside the disposal site were
      characterised by the same species. Regression models indicated that the
      variability in biological structure and secondary production was predominantly
      accounted for by natural variables (e.g., depth, sediment granulometry) with only
      a small amount of residual variability being due to contaminant variables. Thus,
      the elevated levels of certain contaminants in the vicinity of the disposal area
      were not sufficient to result in significant ecological or ecotoxicological
      changes. We ascribe such findings partly to the dispersive nature of the disposal
      site.

PMID- 21868045
TI  - Pigmentation of massive corals as a simple bioindicator for marine water quality.
AB  - Photo-acclimatisation by the algal endosymbionts of scleractinian corals to
      changes in environmental conditions may influence their density and/or the
      concentration of photosynthetic pigments, and hence coral brightness, on short
      time-scales. To examine coral pigmentation as a bioindicator of water quality,
      the brightness of massive corals was quantified using colour charts,
      concentrations of the pigment chlorophyll a and reflectance spectrometry in the
      field and with manipulative experiments. Along a water quality gradient, massive
      Porites became progressively lighter as nutrients decreased and irradiance
      increased. A laboratory experiment showed that Porites nubbins darkened within 25
      days following exposure to reduced water quality. The results of a
      transplantation experiment of Porites nubbins in a manipulation incorporating
      multiple depths and zones of water quality confirmed colony brightness as a
      simple tool to monitor changes in marine water quality, provided effects due to
      other influences on pigmentation, e.g. seawater temperatures, are taken into
      consideration.

PMID- 21868046
TI  - In vitro effects of nonylphenol on functional responses of haemocytes of the
      colonial ascidian Botryllus schlosseri.
AB  - The effects of nonylphenol (NP) on functional responses of haemocytes of the
      colonial ascidian Botryllus schlosseri were evaluated. Haemocytes were exposed to
      0.1, 1 and 10 MUM NP and the effects on haemocyte viability, adhesion,
      morphology, lysosomal membrane stability, phagocytic activity and early apoptosis
      were evaluated. Haemocyte viability and adhesion were not affected by NP.
      Phagocytic activity and the amoebocytic index decreased significantly at all the
      concentrations tested, while exposure of haemocytes to 1 and 10 MUM NP caused a
      significant increase in the diffusion of Neutral Red into the cytosol. The
      percentage of cells positive to Annexin-V (indicative of early apoptosis)
      increased significantly at 1 and 10 MUM NP. Results obtained suggested a
      relationship between NP and alterations in functional responses of haemocytes in
      B. schlosseri. Biomarkers measured resulted sensitive, rapid and reproducible,
      even if their responsiveness will be evaluated after in vivo exposure of animals
      to NP.

PMID- 21868047
TI  - Ezetimibe alone or in combination with pitavastatin prevents kidney dysfunction
      in 5/6 nephrectomized rats fed high-cholesterol.
AB  - We attempted to elucidate the relationship between cholesterol absorption and
      kidney damage by investigating the renoprotective effect of ezetimibe, a
      cholesterol absorption inhibitor, in 5/6 nephrectomized rats (Nx). The Nx or sham
      operated rats (Sham) were fed 1% high-cholesterol diet (HC) containing ezetimibe
      (10 mg/[kg d]), pitavastatin (3 mg/[kg d]), or both for 8 weeks. Pathological
      changes, endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA), and
      oxidative stress were assessed in the kidney. The Sham fed HC exhibited
      hypercholesterolemia and glomerulosclerosis with macrophage infiltration in the
      kidney, and ezetimibe attenuated these changes. The Nx exhibited
      hypercholesterolemia, increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG),
      glomerulosclerosis with macrophage infiltration and interstitial fibrosis, and
      downregulation of eNOS mRNA. The HC increased cholesterol further and worsened
      the kidney damage with increased 8-OHdG. Ezetimibe attenuated the
      hypercholesterolemia, kidney dysfunction, and pathological changes. The
      beneficial effects of ezetimibe were significantly associated with reduced 8-OHdG
      (P < .01). Pitavastatin did not reduce cholesterol or 8-OHdG, but it did
      significantly suppress the kidney damage with upregulated eNOS mRNA by 2.5-fold
      (P < .02). The combination of ezetimibe and pitavastatin synergistically
      ameliorated the kidney damage. The kidney dysfunction and pathological changes
      were significantly associated with cholesterol, markers of cholesterol absorption
      (campesterol and cholestanol), and 8-OHdG (P < .001-.05). Multiple regression
      analysis revealed that the markers of cholesterol absorption were independently
      associated with the kidney damage. Ezetimibe confers renoprotective effects by
      inhibiting cholesterol absorption, which in turn reduces oxidative stress; and
      pitavastatin additively ameliorates kidney damage by increasing NO production via
      mechanisms independent of cholesterol reduction.

PMID- 21868048
TI  - Effect of selenium supplementation with sodium selenite and selenium
      nanoparticles on iron homeostasis and transferrin gene expression in sheep: a
      preliminary study.
AB  - The present research aimed at evaluating the effects of sodium selenite and
      selenium nanoparticles (Se NPs) on iron homeostasis and the expression of
      transferrin and its receptor-binding protein genes. Twenty one Lori-Bakhtiary
      sheep were randomly allocated into 3 groups. Groups 1 and 2 orally received Se
      NPs and sodium selenite (1 mg kg(-1)) for 10 consecutive days, respectively.
      Group 3 served as the control. Blood and sternal bone marrow samples were
      collected at different supplementation intervals. Various factors such as serum
      iron concentration, total iron binding capacity (TIBC), and transferrin
      saturation percent were determined. The expression of transferrin and transferrin
      binding receptor genes was also studied. Results showed a decreasing trend in
      serum iron concentration particularly during the early and middle stages of
      supplementation (0-20 days) with Se NPs or selenium ions. Conversely, the TIBC
      level increased in sera especially during these periods (0-20 days) in animals
      that received selenium NPs or selenium ions. Our results also showed that
      expression of transferrin and its receptor genes was considerably increased
      during supplementation of the animals by both selenium compounds for 10 or 20
      days. After this period, the expression of the mentioned genes significantly
      decreased, especially in animals that received selenium ions.

PMID- 21868049
TI  - Revisiting saw-scaled viper (Echis carinatus) bites in the Jaffna Peninsula of
      Sri Lanka: distribution, epidemiology and clinical manifestations.
AB  - In Sri Lanka, the saw-scaled viper (Echis carinatus) is distributed in the arid,
      dry and sandy coastal plains and in a prospective study we describe its bites in
      the Jaffna peninsula. Of the 304 snake bite admissions to the Jaffna Hospital in
      2009, 217 (71.4%) were bitten by either venomous species or envenomed by
      unidentified snakes. There were 99 (45.6%) reported saw-scaled viper bites, of
      which 26 were confirmed cases. The length of the offending snakes ranged from 228
      310mm and bites mainly occurred in the nearby islands. The median age of the
      confirmed cases was 34 years (range 1.5-72 years); occupations included
      housewives (8, 31%), school children (4, 15%) and farmers (2, 8%). In 18 patients
      (69%), bites occurred in daylight and in 8 (31%) within or near the compounds.
      The fingers were bitten in 8 (31%) and toes/foot in 11 (42%) cases. There were 2
      (8%) dry bites and 19 patients (73%) developed local swelling; one patient
      developed haemorrhagic blisters. In 24 patients (92%), blood incoagulability
      manifested between 40 and 1095min after the bite, and three patients (12%)
      developed spontaneous bleeding. One patient (4%) developed mild acute renal
      dysfunction. The median time for correction of coagulopathy was 802min (range 180
      1669min) with Indian polyvalent antivenom. All recovered. The saw scaled viper is
      responsible for most venomous bites in the Jaffna peninsula.

PMID- 21868051
TI  - Rapid free chlorine decay in the presence of Cu(OH)2: chemistry and practical
      implications.
AB  - A rapid reaction between free chlorine and the cupric hydroxide [Cu(OH)2] solids
      commonly found on pipe walls in premise plumbing can convert free chlorine to
      chloride and rapidly age Cu(OH)2 to tenorite (CuO). This reaction has important
      practical implications for maintaining free chlorine residuals in premise
      plumbing, commissioning of new copper pipe systems, and maintaining low levels of
      copper in potable water. The reaction stoichiometry between chlorine and Cu(OH)2
      is consistent with formation of CuO through a metastable Cu(III) intermediate,
      although definitive mechanistic understanding requires future research. Natural
      levels of silica in water (0-30 mg/L), orthophosphate, and higher pH interfere
      with the rate of this reaction.

PMID- 21868052
TI  - Influence of soil ageing on bioavailability and ecotoxicity of lead carried by
      process waste metallic ultrafine particles.
AB  - Ultrafine particulate matters enriched with metals are emitted into the
      atmosphere by industrial activities and can impact terrestrial and aquatic
      ecosystems. Thus, this study investigated the environmental effects of process
      particles from a lead-recycling facility after atmospheric deposition on soils
      and potential run-off to surface waters. The toxicity of lead-enriched PM for
      ecosystems was investigated on lettuce and bacteria by (i) germination tests,
      growth assays, lead transfer to plant tissues determination and (ii) Microtox
      analysis. The influence of ageing and soil properties on metal transfer and
      ecotoxicity was studied using three different soils and comparing various aged,
      spiked or historically long-term polluted soils. Finally, lead availability was
      assessed by 0.01 M CaCl(2) soil extraction. The results showed that process PM
      have a toxic effect on lettuce seedling growth and on Vibrio fischeri metabolism.
      Soil-PM interactions significantly influence PM ecotoxicity and bioavailability;
      the effect is complex and depends on the duration of ageing. Solubilisation or
      stabilisation processes with metal speciation changes could be involved. Finally,
      Microtox and phytotoxicity tests are sensitive and complementary tools for
      studying process PM ecotoxicity.

PMID- 21868053
TI  - Effects of nano-TiO(2) in combination with ambient UV-irradiation on a leaf
      shredding amphipod.
AB  - Production and use of engineered nanoparticles, such as titanium dioxide
      nanoparticles (nTiO(2)), is increasing worldwide, enhancing their probability to
      enter aquatic environments. However, direct effects of nTiO(2) as well as
      ecotoxicological consequences due to the interactions of nTiO(2) with
      environmental factors like ultraviolet (UV) irradiation on representatives of
      detrital food webs have not been assessed so far. Hence, the present study
      displayed for the first time adverse sublethal effects of nTiO(2) at
      concentrations as low as 0.2 mg L(-1) on the leaf shredding amphipod Gammarus
      fossarum both in presence and absence of ambient UV-irradiation following a 7-d
      exposure. In absence of UV-irradiation, however, the effects seemed to be driven
      by accumulation of nTiO(2) at the bottom of the test vessels to which the
      gammarids were potentially exposed. The adverse sublethal and lethal effects on
      gammarids caused by the combined application of nTiO(2) and ambient UV
      irradiation are suggested to be driven by the formation of reactive oxygen
      species. In conclusion, both the accumulation of nTiO(2) at the bottom of the
      test vessel and the UV induced formation of reactive oxygen species clearly
      affected its ecotoxicity, which is recommended for consideration in the
      environmental risk assessment of nanoparticles.

PMID- 21868050
TI  - Differential virus restriction patterns of rhesus macaque and human APOBEC3A:
      implications for lentivirus evolution.
AB  - The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3;
      A3) family of proteins (A3A-H) are known to restrict various retroviruses and
      retroelements, but the full complement of rhesus macaque A3 proteins remains
      unclear. We report the isolation and characterization of the hA3A homologue from
      rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are
      orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is
      widely expressed in macaque tissues, and is degraded in the presence of the human
      immunodeficiency virus (HIV-1) and simian-human immunodeficiency virus (SHIV)
      genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVDeltavif
      and to a lesser extent HIV-1Deltavif. Unlike hA3A, rhA3A did not inhibit adeno
      associated virus 2 (AAV-2) replication and L1 retrotransposition. These data
      suggest an evolutionary switch in primate A3A virus specificity and provide the
      first evidence that a primate A3A can inhibit lentivirus replication.

PMID- 21868054
TI  - Arsenic speciation in field-collected and laboratory-exposed earthworms Lumbricus
      terrestris.
AB  - Mature Lumbricus terrestris were host soils and leaf litter were collected from a
      former arsenic mine in Devon, UK (Devon Great Consols), a former gold mine in
      Ontario, Canada (Deloro), and an uncontaminated residential garden in Nottingham,
      UK. Arsenic concentrations determined by inductively coupled plasma-mass
      spectrometry (ICP-MS) in soils were 16-348 mg kg(-1), 6.0-239 mg kg(-1) in the
      earthworms and 8.6 mg kg(-1) in leaf litter sampled at Deloro (all dry weight).
      High performance liquid chromatography (HPLC-ICP-MS) analysis revealed arsenite
      (As(III)), arsenate (As(V)) and five organoarsenic species; arsenobetaine (AB),
      methylarsonate (MA(V)), dimethylarsinate (DMA(V)), arsenosugar 1 (glycerol
      sugar), arsenosugar 2 (phosphate sugar), and trimethylarsineoxide (TMAO) in field
      collected L. terrestris. Differences were observed in the variety of
      organoarsenic species present between field sites. Several organoarsenic species
      were observed in the leaf litter (DMA(V), arsenosugar 2 and TMAO) but not AB.
      Depuration resulted in higher concentrations of inorganic As being detected in
      the earthworm whereas the concentration or variety of organoarsenic species was
      unchanged. Commercially sourced L. terrestris were exposed to As contaminated
      soil in laboratory mesocosms (1.0, 98, 183, 236, 324 and 436 mg kg(-1)) without
      leaf litter and were additionally analyzed using X-ray absorption near edge
      structure (XANES). Only inorganic As(III) and As(V) was observed. It is proposed
      that ingestion of leaf litter and symbiotic processes in the natural soil
      environment are likely sources of organoarsenic compounds in field-collected L.
      terrestris.

PMID- 21868055
TI  - Organic pollutants and their correlation with stable isotopes in vegetation from
      King George Island, Antarctica.
AB  - Vegetation samples from King George Island, Antarctica (62 degrees 05'S, 058
      degrees 23'W) were collected in the austral summer of 2004-2005. Lichens (Usnea
      aurantiaco-atra and Usnea antarctica), mosses (Sanionia uncinata, Syntrichia
      princeps and Brachytecium sp.), and one angiosperm (Colobanthus quitensis)
      species were analyzed for persistent organic pollutants as well as delta(13)C and
      delta(15)N stable isotopes. The following contaminants were found above the
      method detection limit (MDL): HCB (0.141-1.06 ng g(-1) dry weight), HCHs (<MDL to
      1.20 ng g(-1) dw), DDTs (<MDL to 1.73 ng g(-1) dw), PCBs (7.76-18.6 ng g(-1) dw)
      and PBDEs (0.146-0.811 ng g(-1) dw). In all cases, levels in mosses were higher
      than in lichens (one order of magnitude higher for OCs), suggesting that specific
      biogeochemical processes were involved in the transport, exposure and absorption
      for each group. Carbon stable isotope ratios showed clearly different ranges for
      lichens (delta13C from -21.130/00 up to -18.430/00) and mosses (-25.990/00 to 
      21.640/00). The only angiosperm species investigated exhibited 13C signature
      within the moss range. A large range of delta15N was found (-7.670/00 to
      20.750/00) and seemed to be related to nitrogen uptake from different animal
      derived sources. Pearson's correlation showed significant results for some
      contaminants (e.g. HCHs/HCB and PCBs/DDTs) and suggested the influence of the
      origin of both nitrogen and pollutants, notably taking secondary sources (animal
      excrements/remains, for instance) into consideration.

PMID- 21868056
TI  - Long-term records of cadmium and silver contamination in sediments and oysters
      from the Gironde fluvial-estuarine continuum - evidence of changing silver
      sources.
AB  - The Gironde fluvial estuarine system is impacted by historic metal pollution
      (e.g. Cd, Zn, Hg) and oysters (Crassostrea gigas) from the estuary mouth have
      shown extremely high Cd concentrations for decades. Based on recent work
      (Chiffoleau et al., 2005) revealing anomalously high Ag concentrations (up to 65
      mg kg(-1); dry weight) in Gironde oysters, we compared long-term (~1955-2001)
      records of Ag and Cd concentrations in reservoir sediment with the respective
      concentrations in oysters collected between 1979 and 2010 to identify the origin
      and historical trend of the recently discovered Ag anomaly. Sediment cores from
      two reservoirs upstream and downstream from the main metal pollution source
      provided information on (i) geochemical background (upstream; Ag: ~0.3 mg kg(-1);
      Cd: ~0.8 mg kg(-1)) and (ii) historical trends in Ag and Cd pollution. The
      results showed parallel concentration-depth profiles of Ag and Cd supporting a
      common source and transport. Decreasing concentrations since 1986 (Cd: from 300
      to 11 mg kg(-1); Ag: from 6.7 to 0.43 mg kg(-1)) reflected the termination of Zn
      ore treatment in the Decazeville basin followed by remediation actions.
      Accordingly, Cd concentrations in oysters decreased after 1988 (from 109 to 26 mg
      kg(-1), dry weight (dw)), while Ag bioaccumulation increased from 38 up to 116 mg
      kg(-1), dw after 1993. Based on the Cd/Ag ratio (Cd/Ag~2) in oysters sampled
      before the termination of zinc ore treatment (1981-1985) and assuming that nearly
      all Cd in oysters originated from the metal point source, we estimated the
      respective contribution of Ag from this source to Ag concentrations in oysters.
      The evolution over the past 30 years clearly suggested that the recent,
      unexplained Ag concentrations in oysters are due to increasing contributions
      (>70% after 1999) by other sources, such as photography, electronics and emerging
      Ag applications/materials.

PMID- 21868057
TI  - Analysis and characterization of cultivable heavy metal-resistant bacterial
      endophytes isolated from Cd-hyperaccumulator Solanum nigrum L. and their
      potential use for phytoremediation.
AB  - This study investigates the heavy metal-resistant bacterial endophytes of Cd
      hyperaccumulator Solanum nigrum L. grown on a mine tailing by using cultivation
      dependent technique. Thirty Cd-tolerant bacterial endophytes were isolated from
      roots, stems, and leaves of S. nigrum L. and classified by amplified ribosomal
      DNA-restriction analysis into 18 different types. Phylogenetic analysis based on
      16S rDNA sequences showed that these isolates belonged to four groups:
      Actinobacteria (43%), Proteobacteria (23%), Bacteroidetes (27%) and Firmicutes
      (7%). All the isolates were then characterized for their plant growth promoting
      traits as well as their resistances to different heavy metals; and the actual
      plant growth promotion and colonization ability were also assessed. Four isolates
      were re-introduced into S. nigrum L. under Cd stress and resulted in Cd
      phytotoxicity decrease, as dry weights of roots increased from 55% to 143% and
      dry weights of above-ground from 64% to 100% compared to the uninoculated ones.
      The total Cd accumulation of inoculated plants increased from 66% to 135% (roots)
      and from 22% to 64% (above-ground) compared to the uninoculated ones. Our
      research suggests that bacterial endophytes are a most promising resource and may
      be the excellent candidates of bio-inoculants for enhancing the phytoremediation
      efficiency.

PMID- 21868058
TI  - Precision dating of the Palaeolithic: a new radiocarbon chronology for the Abri
      Pataud (France), a key Aurignacian sequence.
AB  - This paper presents a new series of AMS dates on ultrafiltered bone gelatin
      extracted from identified cutmarked or humanly-modified bones and teeth from the
      site of Abri Pataud, in the French Dordogne. The sequence of 32 new
      determinations provides a coherent and reliable chronology from the site's early
      Upper Palaeolithic levels 5-14, excavated by Hallam Movius. The results show that
      there were some problems with the previous series of dates, with many
      underestimating the real age. The new results, when calibrated and modelled using
      a Bayesian statistical method, allow detailed understanding of the pace of
      cultural changes within the Aurignacian I and II levels of the site, something
      not achievable before. In the future, the sequence of dates will allow wider
      comparison to similarly dated contexts elsewhere in Europe. High precision dating
      is only possible by using large suites of AMS dates from humanly-modified
      material within well understood archaeological sequences modelled using a
      Bayesian statistical method.

PMID- 21868059
TI  - New vertebral and rib material point to modern bauplan of the Nariokotome Homo
      erectus skeleton.
AB  - The double S shape of the vertebral column is one of the most important
      evolutionary adaptations to human bipedal locomotion, providing an optimal
      compromise between stability and mobility. It is commonly believed that a six
      element long lumbar spine facilitated the critical adoption of lumbar lordosis in
      early hominins, which contrasts with five lumbars in modern humans and four in
      chimpanzees and gorillas. This is mainly based on the juvenile Homo erectus
      skeleton KNM-WT 15000 from Nariokotome, Kenya. Yet, the biomechanical advantage
      of a long lumbar spine is speculative. Here we present new vertebral and rib
      fragments of KNM-WT 15000. They demonstrate that the sixth to the last presacral
      vertebra possesses rib facets and therefore indicate the presence of only five
      lumbar and twelve thoracic segments, as is characteristic of modern humans.
      Moreover, they show that no additional element was located between the sixth to
      the last presacral vertebra and Th11 as suggested in the original description.
      The transition from thoracic to lumbar type orientation of the facet joints that
      takes place at Th11 is thus at the same segment as in over 40% of modern humans,
      suggesting an identical lumbar mobility and capacity for lordosis. Taken
      together, KNM-WT 15000 had one vertebra less than previously thought irrespective
      of whether rib-free lumbar vertebrae or vertebrae that bear lumbar-like articular
      processes are counted. Furthermore, the new rib fragments imply a rearrangement
      of the ribs that results in a symmetrical rib cage. This challenges previous
      claims for idiopathic or congenital scoliosis. We conclude that the bauplan of
      the hominin axial skeleton is more conservative than previously thought.

PMID- 21868060
TI  - Inverse relationship between preoperative radiographic severity and postoperative
      pain in patients with osteoarthritis who have undergone total joint arthroplasty.
AB  - OBJECTIVES: To determine cross-sectionally the influence of risk factors on
      chronic pain following total joint replacement (TJR) of the knee (TKR) or the hip
      (THR). METHODS: Eight hundred sixty post-TKR and 928 post-THR patients were
      studied. Western Ontario and McMaster Osteoarthritis Index pain scores taken on
      average 3.2 years postsurgery were correlated to preoperative radiographic
      severity measured by Kellgren-Lawrence grade (K/L) grade for the knee, Croft
      grade, and minimum joint space width (minJSW) for the hip and presence of
      comorbidities. RESULTS: Known risk factors were able to explain less than 20% of
      the variance in pain scores post-TJR. The presence of chronic widespread pain
      determined a higher risk of high pain in both TKR cases (odds ratio (OR) = 3.15
      95%CI 1.86-5.30) and THR cases (OR = 5.02 95%CI 2.76-9.14). Other risk factors
      common to both TKR and THR pain postsurgery were the presence of depression,
      higher body mass index, younger age, and female gender. Interestingly, low
      radiographic grade at the index joint presurgery (defined as tibiofemoral K/L <3
      for the knee and minJSW >2 mm for the hip) resulted in a significantly increased
      risk of high pain post-TJR (OR = 1.56; 95%CI 1.04-2.36). CONCLUSIONS: The risk
      factors contributing to chronic pain post-TJR remain mostly unknown. Individuals
      with lower preoperative radiographic OA severity undergoing TJR are more likely
      to experience high pain post-TJR.

PMID- 21868061
TI  - Posterior reversible encephalopathy syndrome: an emerging disease manifestation
      in systemic lupus erythematosus.
AB  - OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is a rare feature
      of systemic lupus erythematosus (SLE) that can present with seizures, visual
      disturbance, and/or hypertension. We describe 7 new cases of PRES in SLE patients
      that highlight some of the diagnostic and treatment dilemmas of this condition.
      METHODS: We obtained informed consent from patients for the review of their
      cases. A comprehensive literature search was done to find all published cases of
      PRES in SLE and these were compared with our cohort. RESULTS: Including our
      series, there are 66 cases of PRES in SLE patients published in the English
      literature to date. Our series had 2 main distinguishing features when compared
      with the available literature: only 43% of our patients presented with seizures
      compared with 83 to 95% in the reported literature and over 50% of our cases of
      PRES occurred in newly diagnosed SLE. CONCLUSIONS: PRES is a more frequent
      feature of SLE than previously thought and may be 1 of the presenting
      manifestations of SLE. Whether PRES is a manifestation of SLE disease activity
      and of its treatment or whether it represents a neuropsychiatric manifestation of
      SLE remain to be determined. Consequently there continues to be controversy as to
      whether immunosuppression should be used in addition to supportive measures in
      the treatment of PRES in SLE.

PMID- 21868062
TI  - Comment on: letter to the editor from Clockaerts and Bierma-Zeinstra.

PMID- 21868063
TI  - Association between statin use and lupus-like syndrome using spontaneous reports.
AB  - OBJECTIVES: Several case reports of lupus-like syndrome suggest that statins
      could have triggered the development of this rare autoimmune disease. However,
      data on the association between statin use and lupus-like syndrome are scarce. We
      assessed whether there was an association between statin use and the occurrence
      of lupus-like syndrome. METHODS: A case/noncase study based on individual case
      safety reports listed in the World Health Organization global individual case
      safety reports database (VigiBase) was conducted. According to World Health
      Organization adverse reaction terminology, cases were defined as reports of lupus
      like syndrome. Each case was matched with 5 noncases by age, gender, and time of
      reporting. Use of statins was classified according to the Anatomical Therapeutic
      Chemical classification code system. Covariates, ie, use of corticosteroids,
      immunosuppressive drugs, nonsteroidal anti-inflammatory drugs, antidepressants,
      antiepileptics, proton pump inhibitors, and cardiovascular drugs, were
      determined. Multivariate logistic regression was used to calculate the reporting
      odds ratios with 95% confidence intervals. RESULTS: We identified 3362 reports of
      lupus-like syndrome as cases and 27,092 reports of other adverse drug reactions
      as noncases. Statins were more frequently reported as suspected drug in cases
      (3.2%) than in noncases (1.5%). After adjustment for several covariates, statins
      were associated with the reporting of lupus-like syndrome (reporting odds ratios
      2.01; 95% confidence intervals 1.61-2.51). CONCLUSIONS: We found an association
      between reporting of statins and lupus-like syndrome. Further studies are needed
      to confirm this finding in more detail and establish causality.

PMID- 21868064
TI  - HELLP syndrome and its relationship with antiphospholipid syndrome and
      antiphospholipid antibodies.
AB  - OBJECTIVE: To perform a systematic review of the association between
      antiphospholipid antibodies, antiphospholipid syndrome (APS), and HELLP syndrome
      (Hemolysis; Elevated Liver enzymes; Low Platelet count), describing clinical
      features, outcome, pathophysiological findings, and treatment. METHODS: We
      performed a literature search in PubMed using the following MeSH entry terms:
      HELLP syndrome, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid
      antibodies, and antiphospholipid syndrome. We limited our search to articles
      published in the English literature from 1994 to 2010. RESULTS: We identified 29
      case reports/studies including a total of 51 pregnancies with HELLP syndrome in
      50 patients. The majority of the cases occurred during the 28 to 36 weeks of
      pregnancy. Nausea, vomiting, epigastric, or right upper quadrant pain was the
      most frequently reported symptoms at disease onset. Elevated liver enzymes and
      low platelet count were reported in all studies. Concomitant hypertension and
      proteinuria were reported in 2/3 of the patients. Hepatic infarctions were
      observed in 33.3% pregnancies. However, thrombosis was also reported in the
      central nervous system, deep or superficial vein thrombosis, skin, intestine,
      bone, spleen, and adrenal glands. Treatment is still a matter of debate in HELLP
      syndrome. Aspirin, subcutaneous, intravenous, and oral anticoagulation, and
      prednisone have been used. In addition to the use of plasma exchange and fresh
      frozen plasma administration, intravenous immunoglobulins and plasmapheresis have
      been described. CONCLUSIONS: The incidence of obstetric events in patients with
      APS is a matter of great interest among rheumatology and gynecology and
      obstetrics professionals. The current knowledge that antiphospholipid
      antibodies/APS is not only a thrombotic disease, but also associated with
      microangiopathic features, can explain the greater prevalence of HELLP syndrome
      in these patients.

PMID- 21868065
TI  - A systematic review and mixed treatment comparison of the efficacy of
      pharmacological treatments for fibromyalgia.
AB  - OBJECTIVES: To review the literature on pharmacological treatments for
      fibromyalgia. METHODS: Relative efficacy was estimated in terms of outcome
      measures highlighted by the Outcome Measures in Rheumatology Network using a
      Bayesian mixed treatment comparison (MTC) meta-analysis. Randomized controlled
      trials reporting treatments for fibromyalgia were identified by systematically
      reviewing electronic databases (Cochrane Library, Medline, EMBASE; accessed
      February 2008) and conducting manual bibliographic searches. RESULTS: Forty-five
      randomized controlled trials met the prespecified inclusion criteria for the
      systematic review. There were limited robust clinical data for some therapeutic
      classes (tricyclic antidepressants, analgesics, sedative hypnotics, monoamine
      oxidase inhibitors) and only 21 studies met the more stringent criteria for
      inclusion in the MTC. The majority of studies included in the MTC assessed the
      anticonvulsant pregabalin (n = 5) or the serotonin norepinephrine reuptake
      inhibitors (SNRIs) duloxetine (n = 3) and milnacipran (n = 3). Licensed doses of
      pregabalin and duloxetine were significantly (P < 0.05) more efficacious than
      placebo in terms of absolute reduction in pain, number of "responders" (>=30%
      reduction in pain), or change in Fibromyalgia Impact Questionnaire score
      (pregabalin 450 mg/d only). There was no significant difference between licensed
      doses of pregabalin and duloxetine for these outcomes. However licensed doses of
      pregabalin produced significantly greater improvements in sleep compared with
      milnacipran (as measured by Medical Outcomes Study Sleep Scale). CONCLUSIONS: The
      current study confirms the therapeutic efficacy of pregabalin and the SNRIs,
      duloxetine and milnacipran, in the treatment of fibromyalgia. Given their
      different modes of action, combination therapy with pregabalin plus an SNRI
      should be investigated in future research.

PMID- 21868066
TI  - Botulinum toxin A treatment of Raynaud's phenomenon: a review.
AB  - OBJECTIVES: Botulinum toxin A has conventionally been used in the upper extremity
      to treat spasticity resulting from stroke, paraplegia, and dystonia. Recently, it
      has been used to relieve symptoms of vasospasm in Raynaud's phenomenon. This
      review summarizes the current literature on botulinum toxin A in the treatment of
      Raynaud's phenomenon and examines the proposed mechanisms of action, suggested
      techniques of administration, and clinical efficacy. METHODS: An Ovid MEDLINE
      search from 1950 to September 2010 was performed to identify any reports on the
      use of Botulinum toxin in the treatment of Raynaud's disease or associated
      vasoconstrictive disorders. All studies pertaining to "Raynaud's disease,"
      "Raynaud's," or "vasoconstriction" were queried and meshed with a secondary
      search of studies pertaining to "botox" or "botulinum toxin type A." These
      reports were meshed and subsequently limited to human studies. All studies that
      met criteria were included and their outcomes evaluated and summarized. RESULTS:
      Since 2004, there have been 5 studies that have evaluated the use of Botulinum
      Toxin A for the treatment of Raynaud's. In each study, patients received a range
      of botulinum toxin injections (10-100 units) in their fingers and hands. The
      studies have many limitations (lack of controls, variable severity of disease,
      variability of dosing) but all report favorable clinical results. All showed
      overall improvement in patient pain as well as a reduction in soft tissue
      ulceration. CONCLUSIONS: Initial reports on the use of botulinum toxin A for
      Raynaud's phenomenon are promising. Larger controlled trials with improved study
      design are warranted. A better understanding of the mechanism of action,
      appropriate dose and dose frequency, and the efficacy relative to other medical
      and surgical treatments requires investigation.

PMID- 21868067
TI  - Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated
      leukopenia.
AB  - OBJECTIVE: We describe 4 patients who presented with palpable purpura, arthralgia
      or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA)
      positivity most likely as a result of a hypersensitivity reaction to cocaine
      levamisole induced vasculopathy. METHODS: Cases were seen and reviewed in both
      the inpatient consult service and the outpatient clinics at Rhode Island Hospital
      from August 2009 to August 2010. Clinical characteristics as well as pertinent
      laboratory parameters were also reviewed and corroborated with a review of the
      present literature. RESULTS: We describe 3 cases of cocaine-levamisole-related
      cutaneous vasculitis with or without associated neutropenia, and 1 case of severe
      neutropenia with oral mucosal ulceration. Further serologic studies revealed
      maximum titers of ANCA mostly in a perinuclear pattern. Antimyeloperoxidase
      tested negative or mildly elevated in our cohort. Three patients with neutropenia
      had positive antigranulocyte IgM antibody. Nonsteroidal anti-inflammatory drugs
      were effective as first-line treatment for joint pain. The use of colchicine and
      systemic corticosteroid was employed to manage severe and persistent skin
      lesions. CONCLUSIONS: Cocaine-levamisole-related cutaneous vasculitis with
      leukopenia is a diagnosis of exclusion, but this diagnosis should be strongly
      considered in patients with a history of cocaine abuse who present with a tetrad
      of cutaneous manifestations consisting of palpable purpura or bullae with ear
      involvement, arthralgias, leukopenia, and positive ANCA in high titers and
      negative Antimyeloperoxidase, when other infectious or idiopathic vasculitic
      entities have been excluded.

PMID- 21868068
TI  - Gonadotropin releasing hormone agonists may minimize cyclophosphamide associated
      gonadotoxicity in SLE and autoimmune diseases.
AB  - OBJECTIVE: Since young women undergoing cyclophosphamide pulse therapy may suffer
      premature ovarian failure (POF) in almost 50% of cases, we examined the ability
      of GnRH-a administration to minimize the gonadotoxicity associated with
      cyclophosphamide pulse therapy (CPT). METHODS: Retrospective analysis of medical
      charts of 44 women (age 16-38 years) who received CPT for autoimmune diseases. In
      33 patients a monthly depot injection of GnRH-a was started before the alkylating
      agent. The ovarian function [spontaneous menstrual bleeding, hormonal profile,
      (FSH, LH, E(2), progesterone) pelvic sonography, and conceptions] was evaluated,
      1 to 10 years after CPT. RESULTS: In the GnRH-a group, 30 women resumed cyclic
      ovarian function; 1 (a 37-year-old patient) developed POF (3%), and 2 were lost
      to follow-up. In the control (no GnRH-a) group, 5 of 11 patients suffered POF
      (45%). The mean age in the study group was 25.6 +/- 5.2 years compared with 29.3
      +/- 5.8 years in the control group, and the mean cumulative cyclophosphamide dose
      was 9.9 g compared to 10.9 g, respectively. The difference in the long-term POF
      remained significant even after adjusting the groups for comparable age and
      cumulative cyclophosphamide doses. CONCLUSION: GnRH-a decreases cyclophosphamide
      associated gonadotoxicity and POF in young women with systemic lupus
      erythematosus and other autoimmune diseases. Therefore this treatment should be
      considered and recommended to every young woman before gonadotoxic chemotherapy.

PMID- 21868069
TI  - Socioeconomic and occupational risk factors for venous thromboembolism in Sweden:
      a nationwide epidemiological study.
AB  - Our aims were to investigate possible associations between hospitalisation for
      venous thromboembolism (VTE) and socioeconomic and occupational factors. A
      nationwide database was constructed by linking Swedish census data to the
      Hospital Discharge Register (1990-2007). Hospital diagnoses of VTE were based on
      the International Classification of Diseases. Standardised incidence ratios were
      calculated for different socioeconomic and occupational groups. A total of 43063
      individuals aged >20 years were hospitalised for VTE. Individuals with >12 years
      of education were at lower risk for VTE. Blue-collar workers, farmers, and non
      employed individuals had higher risks for VTE, and white collar workers and
      professionals lower risks. In males and/or females, risks for VTE were increased
      for assistant nurses; farmers; miners and quarry workers; mechanics, iron and
      metalware workers; wood workers; food manufacture workers; packers; loaders and
      warehouse workers; public safety and protection workers; cooks and stewards; home
      helpers; building caretakers; and cleaners. Decreased risks were observed for
      technical, chemical, physical, and biological workers; physicians; dentists;
      nurses; other health and medical workers; teachers, religious, juridical, and
      other social science-related workers; artistic workers; clerical workers; sale
      agents; and fishermen, whalers and sealers. High educational level and several
      occupations requiring high levels of education were protective against VTE, while
      the risks for VTE were increased for farmers, blue-collar workers and non
      employed individuals. The mechanisms are unknown but it might involve persistent
      psychosocial stress related to low socioeconomic and occupational status.

PMID- 21868070
TI  - Protein Z concentration in multiple myeloma patients.

PMID- 21868071
TI  - Alterations of profibrinolytic receptor annexin A2 in pre-eclampsia: a possible
      role in placental thrombin formation.
AB  - INTRODUCTION: Deficient fibrinolytic activity due to alterations of
      profibrinolytic receptor annexin A2 has been shown to be related to increased
      thrombosis. We compared the expression of annexin A2 in pre-eclampsia with that
      in normal pregnancies and investigated its relationship to placental thrombin
      formation. MATERIALS AND METHODS: Sixty patients with pre-eclampsia and 30
      matched normal pregnant controls were included in the study. Expression of
      annexin A2 mRNA in placental tissues was analyzed using quantitative RT-PCR.
      Annexin A2 protein in placentas as well as blood was determined by western blot
      analysis and immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was
      used to detect the presence of anti- annexin A2 antibodies in peripheral maternal
      blood. RESULTS: The expression of annexin A2 mRNA in placentas was significantly
      decreased in pre-eclampsia compared to normal pregnancies. Levels of annexin A2
      protein in placentas as well as in peripheral maternal blood were also
      significantly reduced in patients with pre-eclampsia compared with healthy
      pregnant women. High titers of anti- annexin A2 antibodies were more frequently
      detected in pre-eclampsia group. Decreased levels of annexin A2 expression and
      the presence of anti-annexin A2 antibodies were associated with increased
      placental thrombosis. CONCLUSION: The down regulation of annexin A2 expression
      and the presence of anti-annexin A2 antibodies were correlated to PE and may
      increase placental thrombin formation.

PMID- 21868072
TI  - The effects of acute and chronic psychological stress on bladder function in a
      rodent model.
AB  - OBJECTIVE: Psychological stress plays a role in the exacerbation of functional
      lower urinary tract disorders, such as painful bladder syndrome and overactive
      bladder. To better understand the mechanism underlying this relationship, we
      characterized changes in micturition, anxiety-related behavior, and bladder
      pathology in rats exposed to repeated water avoidance (WA) stress. METHODS:
      Twenty-four Wistar rats were subjected to WA stress or sham. Immediately after
      acute (day 1) and chronic (day 10) stress or sham, rats were placed in a
      metabolic cage for a 2-hour voiding behavior assessment. Voiding parameters were
      compared with baseline values obtained before stress. Four animals from each
      group were sacrificed on day 10 and bladders harvested for histologic and gene
      expression studies. The remaining 8 animals per group underwent repeated voiding
      assessment every 3 days for 1 month followed by 10 days of repeat WA stress or
      sham. Bladder histology and gene expression were studied. RESULTS: Rats exposed
      to WA stress developed a significant increase in micturition frequency and
      decrease in latency to void, voiding interval, and volume of first void compared
      with sham and baseline. Alterations in micturition persisted for approximately 1
      month. Stressed rats showed increased fecal pellet excretion and anxiety-like
      behavior. In addition, bladder specimens from stressed animals revealed increased
      angiogenesis, and increased total and activated mast cells. CONCLUSION: In rats,
      repeated psychological stress results in lasting alterations in micturition
      frequency, interval, and volume. This rodent model may represent a valid tool for
      studying syndromes characterized by increased urinary frequency.

PMID- 21868073
TI  - Sputum inflammatory cells from patients with allergic rhinitis and asthma have
      decreased inflammasome gene expression.

PMID- 21868074
TI  - Early-onset monocyte-B-natural killer-dendritic cells' deficiency successfully
      treated with hematopoietic stem cell transplantation.

PMID- 21868075
TI  - Symptom-based classification of wheeze: how does it work in infants?

PMID- 21868076
TI  - Pathogenesis of chronic rhinosinusitis: inflammation.
AB  - Chronic rhinosinusitis (CRS) is a heterogeneous group of inflammatory diseases of
      the nasal and paranasal cavities either accompanied by polyp formation (CRSwNP)
      or without polyps (CRSsNP). CRSsNP and CRSwNP are prevalent medical conditions
      associated with substantial impaired quality of life, reduced workplace
      productivity, and serious medical treatment costs. Despite recent research
      evidence that contributes to further unveiling the pathophysiology of these
      chronic airway conditions, the cause remains poorly understood and appears to be
      multifactorial. A diverse spectrum of alterations involving histopathology,
      inflammatory cell and T-cell patterns, remodeling parameters (eg, TGF-beta),
      eicosanoid and IgE production, microorganisms, and epithelial barrier
      malfunctions is reported in the search to describe the pathogenesis of this
      heterogeneous group of upper airway diseases. Furthermore, novel evidence
      indicates considerable heterogeneity within the CRSwNP subgroup determining the
      risk of comorbid asthma. The characterization of specific disease subgroups is a
      challenging scientific and clinical task of utmost importance in the development
      of diagnostic tools and application of individualized treatments. This review
      focuses on recent evidence that sheds new light on our current knowledge
      regarding the inflammatory process of CRS to further unravel its pathogenesis.

PMID- 21868077
TI  - Critical role for programmed death 1 signaling and protein kinase B in augmented
      regulatory T-cell induction in cord blood.

PMID- 21868078
TI  - Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis
      in a randomized, double-masked, controlled 2-year study.

PMID- 21868079
TI  - T cell-mediated acute localized exanthematous pustulosis caused by finasteride.
AB  - A 21-year-old man presented with multiple erythematous nonfollicular papules
      partially confluent to plaques on his breast and lower abdomen that had been
      present for 1 month. Grouped pustules were present under the right breast. The
      patient had been taking finasteride over the past 3 months for androgenetic
      alopecia. His medical history was negative for psoriasis. Our initial
      differential diagnosis included dyskeratosis follicularis Darier, allergic
      contact dermatitis, infectious folliculitis, varicella zoster virus infection,
      fixed drug eruption, and IgA pemphigus. The white blood cell count and
      differential were within the normal limits. Results of viral cultures and PCR, as
      well as bacterial and fungal cultures of skin lesions proved negative. A lesional
      biopsy specimen showed a slight psoriasiform acanthosis in association with
      spongiosis and infiltration of both the epidermis and dermis by neutrophils and
      eosinophils, resulting in formation of subcorneal, intraepidermal, and
      subepidermal pustules. The results of direct immunofluorescence were negative,
      excluding an IgA pemphigus. The result of a lymphocyte transformation test was
      positive for finasteride. On the basis of the time relationship between the
      administration of finasteride and the development of the skin disease in
      combination with symptoms resolution on cessation of the drug, the histologic
      findings, and the positive lymphocyte transformation test result, we consider
      this to be an unusual type of acute generalized exanthematous pustulosis defined
      as acute localized exanthematous pustulosis caused by finasteride. Within 4 weeks
      after withdrawal of finasteride, the rash resolved without any specific therapy.
      Transient discrete residual hyperpigmentation and scaling were present. The
      patient refused an oral provocation challenge.

PMID- 21868080
TI  - Effects of purine nucleoside phosphorylase deficiency on thymocyte development.
AB  - BACKGROUND: Inherited or acquired defects in purine nucleoside phosphorylase
      (PNP) impair purine metabolism, as well as the survival and function of T
      lymphocytes. However, the effects of PNP deficiency on thymocyte development are
      not well known. OBJECTIVES: We sought to study thymocyte development in PNP
      deficient (PNP-KO) mice. METHODS: Maturation, proliferation, and apoptosis were
      determined in thymocytes from PNP-KO mice and hematopoietic stem cells from these
      mice grown ex vivo into thymocyte-like cells. RESULTS: Reduced percentages of
      CD4(+)CD8(+) double-positive (DP) thymocytes with normal percentages of CD4(
      )CD8(+) and CD4(+)CD8(-) single-positive thymocytes were found in the thymi of
      PNP-KO mice. Similarly, reduced DP-like thymocytes grew ex vivo from
      hematopoietic stem cells of PNP-KO mice. Thymi of PNP-KO mice contained increased
      apoptotic DP thymocytes. Increased apoptosis of PNP-deficient DP thymocytes
      occurred after exposure to deoxyguanosine (dGuo), although not after Fas
      ligation, and could be prevented by restoring PNP activity within the cells. In
      DP thymocytes from PNP-KO mice, dGuo caused mitochondrial membrane potential
      dissipation and induced release of cytochrome c from the mitochondria followed by
      nuclear DNA fragmentation. Inhibition of the caspase pathway prevented dGuo
      induced nuclear DNA fragmentation but not mitochondrial membrane potential
      dissipation, indicating that PNP deficiency induces apoptosis that is initiated
      in the mitochondria of DP thymocytes. 5-Bromo-2-deoxyuridine incorporation
      demonstrated that PNP deficiency does not interfere with DP or single-positive
      thymocyte proliferation. CONCLUSIONS: PNP is important for the survival of DP
      thymocytes. Accumulation of dGuo in cases of PNP deficiency leads to mitochondria
      initiated apoptosis of DP thymocytes, which can be prevented by restoring PNP
      activity in the cells.

PMID- 21868081
TI  - Self-disclosure to the best friend: friendship quality and internalized sexual
      stigma in Italian lesbian and gay adolescents.
AB  - This study is the first contribution to the understanding of gender differences
      in best friendship patterns of adolescents sexual minorities. We explored
      friendship patterns, self-disclosure, and internalized sexual stigma in an
      Italian sample of lesbian (N = 202) and gay (N = 201) adolescents (aged 14-22
      years). We found gender differences in cross-sex and cross-orientation patterns
      of best friendship. Gay men (52%) reported more cross-sex friendships than
      lesbians (20%). The 52% of participants had cross-orientation friendships, and no
      differences were found between lesbians and gay men. Lesbian and gay men with a
      cross-orientation best friend showed a lower level of internalized sexual stigma.
      Gay men with cross-orientation friendship showed a low level of internalized
      sexual stigma and less conflict with a best friend. For gay men and lesbian
      participants, self-disclosure to the best friend was better predicted by
      internalized sexual stigma and self-disclosure. Future studies may provide direct
      comparisons between heterosexual and sexual minority individuals.

PMID- 21868082
TI  - A practitioner's view: invited commentary.

PMID- 21868083
TI  - Identity and civic engagement in adolescence.
AB  - The purpose of this study was to examine the links between identity (statuses and
      processes) and adolescent civic engagement (volunteer and political
      participation). Participants were 392 Italian high school students (42% males)
      aged 14-20 years (M(age) = 16.23 years; SD(age) = 1.53) who completed a self
      report questionnaire. First, using a person-centered approach, we found that
      achieved adolescents were more involved in volunteer activities, reported higher
      civic efficacy, and stronger aspirations to contribute to their communities than
      their diffused counterparts. Second, by means of a variable-centered approach, we
      demonstrated that the link between identity processes (i.e., commitment and in
      depth exploration) and past and future volunteer and political participation was
      mediated by social responsibility. Implications of the findings for current
      understanding of the link between adolescent identity formation and civic
      engagement are discussed and suggestions for future research are outlined.

PMID- 21868084
TI  - Accurate hypertension diagnosis is key in efficient control.

PMID- 21868085
TI  - The cryoglobulinaemias.
AB  - Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less
      than 37 degrees C and produce organ damage through two main pathways: vascular
      sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune
      mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia).
      Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped
      into infections, autoimmune disorders, and malignancies; the most common cause is
      infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed
      when a patient has typical organ involvement (mainly skin, kidney, or peripheral
      nerve) and circulating cryoglobulins. Cutaneous purpura is the most common
      manifestation of cryoglobulinaemic vasculitis. The most frequently affected
      internal organs are the peripheral nerves, kidneys, and joints. The course varies
      widely and prognosis is influenced by both cryoglobulinaemic damage to vital
      organs and by comorbidities associated with underlying diseases. More than 90% of
      cases of cryoglobulinaemia have a known underlying cause; therefore treatment is
      focused on the cause of the disorder rather than merely symptomatic relief.
      Studies suggest that both combined or sequential antiviral therapies and targeted
      biological treatments might be more effective than monotherapy.

PMID- 21868086
TI  - Cost-effectiveness of options for the diagnosis of high blood pressure in primary
      care: a modelling study.
AB  - BACKGROUND: The diagnosis of hypertension has traditionally been based on blood
      pressure measurements in the clinic, but home and ambulatory measurements better
      correlate with cardiovascular outcome, and ambulatory monitoring is more accurate
      than both clinic and home monitoring in diagnosing hypertension. We aimed to
      compare the cost-effectiveness of different diagnostic strategies for
      hypertension. METHODS: We did a Markov model-based probabilistic cost
      effectiveness analysis. We used a hypothetical primary-care population aged 40
      years or older with a screening blood-pressure measurement greater than 140/90 mm
      Hg and risk-factor prevalence equivalent to the general population. We compared
      three diagnostic strategies-further blood pressure measurement in the clinic, at
      home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted
      life years, and cost-effectiveness. FINDINGS: Ambulatory monitoring was the most
      cost-effective strategy for the diagnosis of hypertension for men and women of
      all ages. It was cost-saving for all groups (from -L56 [95% CI -105 to -10] in
      men aged 75 years to -L323 [-389 to -222] in women aged 40 years) and resulted in
      more quality-adjusted life years for men and women older than 50 years (from
      0.006 [0.000 to 0.015] for women aged 60 years to 0.022 [0.012 to 0.035] for men
      aged 70 years). This finding was robust when assessed with a wide range of
      deterministic sensitivity analyses around the base case, but was sensitive if
      home monitoring was judged to have equal test performance to ambulatory
      monitoring or if treatment was judged effective irrespective of whether an
      individual was hypertensive. INTERPRETATION: Ambulatory monitoring as a
      diagnostic strategy for hypertension after an initial raised reading in the
      clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory
      monitoring are counterbalanced by cost savings from better targeted treatment.
      Ambulatory monitoring is recommended for most patients before the start of
      antihypertensive drugs. FUNDING: National Institute for Health Research and the
      National Institute for Health and Clinical Excellence.

PMID- 21868087
TI  - Short-term variability of multiple biomarker response in fish from estuaries:
      Influence of environmental dynamics.
AB  - Short-term variability in biomarker responses and the effects of temperature and
      salinity variation were explored in three fish species (Dicentrarchus labrax,
      Solea senegalensis and Pomatoschistus microps) occurring in the Tejo estuary.
      Short-term variability in biomarkers was observed in all species although no
      pattern was discerned over time (days to weeks). Antioxidant enzymes activity
      (superoxide dismutase (SOD) and catalase (CAT)) showed low temporal variability,
      indicating some constancy or baseline level in antioxidant responses. Only CAT
      activity in S. senegalensis was correlated with temperature, suggesting that
      exposure to contaminants triggered antioxidant acclimation. Higher short-term
      variability was observed in xenobiotic biotransformation enzymes activity (phase
      I ethoxyresorufin O-deethylase (EROD) and phase II glutathione S-transferase
      (GST)). Yet a significant correlation between EROD and GST in D. labrax and S.
      senegalensis suggests a concomitant response to contaminants. Moreover the lack
      of correlation between xenobiotic biotransformation enzymes and abiotic variables
      on concordant time scales, suggest a high specificity of these biomarkers to
      chemical exposure, rather than high variability due to environmental dynamics.

PMID- 21868089
TI  - The effect of hydration on molecular chain mobility and the viscoelastic behavior
      of resilin-mimetic protein-based hydrogels.
AB  - The outstanding rubber-like elasticity of resilin and resilin-mimetic proteins
      depends critically on the level of hydration. In this investigation, water vapor
      sorption and the role of hydration on the molecular chain dynamics and
      viscoelastic properties of resilin-mimetic protein, rec1-resilin is investigated
      in detail. The dynamic and equilibrium swelling behavior of the crosslinked
      protein hydrogels with different crosslink density are reported under various
      controlled environments. We propose three different stages of hydration;
      involving non-crystallizable water, followed by condensation or clustering of
      water around the already hydrated sites, and finally crystallizable water. The
      kinetics of water sorption for this engineering protein is observed to be
      comparable to hydrophilic polymers with a diffusion coefficient in the range of
      10(-7) cm(2) s(-1). From the comparison between the absorption and desorption
      isotherms at a constant water activity, it has been observed that rec1-resilin
      exhibits sorption hysteresis only for the tightly bound water. Investigation of
      molecular mobility using differential scanning calorimetry, indicates that
      dehydrated crosslinked rec1-resilin is brittle with a glass transition
      temperature (T(g)) of >180  degrees C, which dramatically decreases with
      increasing hydration; and above a critical level of hydration rec1-resilin
      exhibits rubber-like elasticity. Nanoindentation studies show that even with
      little hydration (<10%), the mechanical properties of rec1-resilin gels change
      dramatically. Rheological investigations confirm that the equilibrium-swollen
      crosslinked rec1-resilin hydrogel exhibits outstanding elasticity and resilience
      of ~ 92%, which exceeds that of any other synthetic polymer and biopolymer
      hydrogels.

PMID- 21868088
TI  - mRNA-Lipoplex loaded microbubble contrast agents for ultrasound-assisted
      transfection of dendritic cells.
AB  - In cancer immunotherapy the immune system should be triggered to specifically
      recognize and eliminate tumor cells in the patient's body. This could be achieved
      by loading dendritic cells (DCs) with tumor-associated antigens (TAAs). This can
      be achieved by transfecting DCs with messenger RNA encoding a tumor-associated
      antigen. Here we demonstrate transient transfection of dendritic cells by means
      of mRNA-lipoplexes bound to microbubbles. Microbubble-attached lipoplexes were
      introduced into the cells by applying ultrasound. Our data demonstrate that
      ultrasound-mediated delivery of mRNA-complexes led to efficient transfection of
      DCs. When mRNA encoding luciferase was used, maximal levels of the enzyme
      activity were detected 8 h after ultrasound application. Upon longer incubation
      protein expression gradually declined. This treatment did not affect viability of
      the cells. Intracellular localisation of mRNA-lipoplexes in DCs was determined by
      flow cytometry using fluorescently labeled lipoplexes. Over 50% of DCs contained
      fluorescently labeled mRNA-complexes. In the absence of additional maturation
      signals, transfection of immature DCs with mRNA-lipoplex loaded microbubbles and
      ultrasound application induced only a minor shift in the expression level of
      maturation markers (CD40 and CD86). However, in the presence of the activation
      stimulus (LPS), cells were able to further mature as shown by a significant up
      regulation of CD40 expression. Thus, our results demonstrate that mRNA-lipoplex
      loaded microbubbles can serve as an applicable and safe tool for efficient mRNA
      transfection of cultured DCs.

PMID- 21868090
TI  - Promotion of osteoblast differentiation in 3D biomaterial micro-chip arrays
      comprising fibronectin-coated poly(methyl methacrylate) polycarbonate.
AB  - Due to the architecture of solid body tissues including bone, three-dimensional
      (3D) in vitro microenvironments appear favorable, since herein cell growth
      proceeds under more physiological conditions compared to conventional 2D systems.
      In the present study we show that a 3D microenvironment comprising a fibronectin
      coated PMMA/PC-based micro-chip promotes differentiation of primary human
      osteoblasts as reflected by the densely-packed 3D bone cell aggregates and
      expression of biomarkers indicating osteoblast differentiation. Morphogenesis and
      fluorescence dye-based live/dead staining revealed homogenous cell coverage of
      the microcavities of the chip array, whereat cells showed high viability up to 14
      days. Moreover, Azur II staining proved formation of uniform sized multilayered
      aggregates, exhibiting progressive intracellular deposition of extracellular bone
      matrix constituents comprising fibronectin, osteocalcin and osteonectin from day
      7 on. Compared to 2D monolayers, osteoblasts grown in the 3D chip environment
      displayed differential mostly higher gene expression for osteocalcin,
      osteonectin, and alkaline phosphatase, while collagen type I remained fairly
      constant in both culture environments. Our results indicate that the 3D
      microenvironment, based on the PMMA biomaterial chip array promotes osteoblast
      differentiation, and hereby renders a promising tool for tissue-specific in vitro
      preconditioning of osteoblasts designated for clinically-oriented bone
      augmentation or regeneration.

PMID- 21868091
TI  - Genome wide expression profile in human HTR-8/Svneo trophoblastic cells in
      response to overexpression of placental alkaline phosphatase gene.
AB  - During pregnancy, placental growth allows the adaptation of the feto-maternal
      unit to fetal requirements. Placental alkaline phosphatase (PLAP) is a
      phosphomonoesterase produced increasingly until term by the placenta and also
      ectopically in some tumors. To precise the role of this enzyme in the placenta,
      we analyzed the genome wide expression profile of HTR-8/Svneo trophoblastic cells
      after overexpression of the alkaline phosphatase gene (ALPP). We showed that ALPP
      overexpression mainly altered expression of genes implicated in cellular growth
      and proliferation. These results were confirmed by the study of cellular effects
      in HTR-8/Svneo cells overexpressing ALPP and in HTR-8/Svneo cells in which ALPP
      expression was suppressed by siRNA. We showed that PLAP exerts a positive effect
      on DNA replication and acts as a proliferative factor in trophoblastic cells.

PMID- 21868092
TI  - TRPV1, TRPA1, and CB1 in the isolated vagus nerve--axonal chemosensitivity and
      control of neuropeptide release.
AB  - Vagal sensory afferents innervating airways and abdominal tissues express TRPV1
      and TRPA1, two depolarizing calcium permeable ion channels playing a major role
      in sensing environmental irritants and endogenous metabolites which cause
      neuropeptide release and neurogenic inflammation. Here we have studied axonal
      chemosensitivity and control of neuropeptide release from the isolated rat and
      mouse vagus nerve by using prototypical agonists of these transduction channels -
      capsaicin, mustard oil and the specific endogenous activators, anandamide (methyl
      arachidonyl ethanolamide, mAEA), and acrolein, respectively. Capsaicin evoked
      iCGRP release from the rat vagus nerve with an EC50 of 0.12 MUM. Co-application
      of mAEA had a dual effect: nanomolar concentrations of mAEA (0.01 MUM)
      significantly reduced capsaicin-evoked iCGRP release while concentrations >= 1
      MUM mAEA had sensitizing effects. Only 100 MUM mAEA directly augmented iCGRP
      release by itself. In the mouse, 310 MUM mAEA increased release in wildtype and
      TRPA1-/- mice which could be inhibited by capsazepine (10 MUM) and was completely
      absent in TRPV1-/- mice. CB1-/- and CB1/CB2 double -/- mice equally displayed
      increased sensitivity to mAEA (100 MUM) and a sensitizing effect to capsaicin, in
      contrast to wildtypes. Acrolein and mustard oil (MO)--at MUM concentrations-
      induced a TRPA1-dependent iCGRP release; however, millimolar concentrations of
      mustard oil (>1mM) evoked iCGRP release by activating TRPV1, confirming recent
      evidence for TRPV1 agonism of high mustard oil concentrations. Taken together, we
      present evidence for functional expression of excitatory TRPV1, TRPA1, and
      inhibitory CB1 receptors along the sensory fibers of the vagus nerve which lend
      pathophysiological relevance to the axonal membrane and the control of
      neuropeptide release that may become important in cases of inflammation or
      neuropathy. Sensitization and possible ectopic discharge may contribute to the
      development of autonomic dysregulation in visceral tissues that are innervated by
      the vagus nerve.

PMID- 21868093
TI  - Inhibiting HDACs in a preclinical model of HTLV-1-induced adult T-cell lymphoma.

PMID- 21868094
TI  - Mercury bioaccumulation and biomagnification in Ozark stream ecosystems.
AB  - Crayfish (Orconectes spp.), Asian clam (Corbicula fluminea), northern hog sucker
      (hog sucker; Hypentelium nigricans), and smallmouth bass (smallmouth; Micropterus
      dolomieu) from streams in southeastern Missouri (USA) were analyzed for total
      mercury (HgT) and for stable isotopes of carbon (delta13C), nitrogen (delta15N),
      and sulfur (delta34S) to discern Hg transfer pathways. HgT concentrations were
      generally lowest in crayfish (0.005-0.112 MUg/g dw) and highest in smallmouth
      (0.093-4.041 MUg/g dw), as was delta15N. HgT was also lower and delta15N was
      higher in all biota from a stream draining a more heavily populated historical
      lead-zinc mining area than from similar sites with mostly undeveloped forested
      watersheds. delta13C in biota was lowest at spring-influenced sites, reflecting
      CO2 inputs and temperature influences, and delta34S increased from south to north
      in all taxa. However, HgT was not strongly correlated with either delta13C or
      delta34S in biota. Trophic position (TP) computed from crayfish delta15N was
      lower in hog suckers (mean=2.8) than in smallmouth (mean=3.2), but not at all
      sites. HgT, delta13C, delta34S, and TP in hog suckers increased with total length
      (length) at some sites, indicating site-specific ontogenetic diet shifts. Changes
      with length were less evident in smallmouth. Length-adjusted HgT site means in
      both species were strongly correlated with HgT in crayfish (r2=0.97, P<0.01), but
      not with HgT in Corbicula (r2=0.02, P>0.05). ANCOVA and regression models
      incorporating only TP and, for hog suckers, length, accurately and precisely
      predicted HgT concentrations in both fish species from all locations. Although
      low compared to many areas of the USA, HgT (and therefore methylmercury)
      concentrations in smallmouth and hog suckers are sufficiently high to represent a
      threat to human health and wildlife. Our data indicate that in Ozark streams, Hg
      concentrations in crayfish are at least partly determined by their diet, with
      concentrations in hog suckers, smallmouth, and possibly other higher-level
      consumers largely determined by concentrations in crayfish and other primary and
      secondary consumers, fish growth rates, and TP.

PMID- 21868095
TI  - Carbofuran effects in soil nematode communities: using trait and taxonomic based
      approaches.
AB  - This work intends to implement the use of native soil nematode communities in
      ecotoxicological tests using a model pesticide and two geographically nematode
      communities (Mediterranean and sub-tropical) in order to obtain new perspectives
      on the evaluation of the toxic potential of chemical substances. The
      environmental condition of the nematode communities was described using a trait
      based approach (grouping the organisms according to their feeding traits) and a
      traditional taxonomic method (identification to family level). Effects on total
      nematode abundance, number of families and abundance of nematode feeding groups
      as well as potential shifts in both trophic and family structure were assessed.
      Agricultural soils from Curitiba (Brazil) and Coimbra (Portugal) were sampled and
      the corresponding nematode communities were extracted. Part of the collected soil
      was defaunated and spiked with four doses of a carbofuran commercial formulation.
      Afterwards each of the replicates was inoculated with a nematode suspension
      containing ~200 or 300 nematodes. After 14 and 28 d of exposure the nematodes
      were extracted, counted and identified at family level and separately classified
      according to their feeding traits. The patterns of nematode responses revealed a
      decrease in the total abundance and a reduction in the number of families.
      Despite the similar effects observed for both communities, statistically
      significant toxic effects were only found within the Portuguese community. The
      total nematode abundance was significantly reduced at the highest carbofuran
      concentrations and significant shifts in the family structure were detected.
      However, the trophic structure, i.e., the contribution of each feeding group for
      the overall community structure, did not significantly change along the
      contamination gradient. Results showed that using such a trait-based approach may
      increase the ecological relevance of toxicity data, by establishing communalities
      in the response to a chemical from two different taxonomic communities, although
      with potential loss of information on biodiversity of the communities.

PMID- 21868096
TI  - Space artifact or Nazi weapon? Displaying the Smithsonian's V-2 missile, 1976
      2011.

PMID- 21868097
TI  - Factor H gene variants in Japanese: its relation to atypical hemolytic uremic
      syndrome.
AB  - Mutations and polymorphisms of factor H gene (FH1) are known to be closely
      involved in the development of atypical hemolytic uremic syndrome (aHUS). Several
      groups have identified disease risk mutations and polymorphisms of FH1 for the
      development of aHUS, and have investigated frequencies of aHUS in a number of
      ethnic groups. However, such studies on Japanese populations are limited. In the
      present study, we analyzed FH1 in Japanese aHUS patients and healthy volunteers,
      and examined whether those variants impacted on a tendency for the development of
      aHUS in Japanese populations. Similar to previous studies, we found that a high
      frequency of FH1 mutations, located in exon 23 of FH1, encodes short consensus
      repeat 20 in C-terminal end of factor H molecule in patients with aHUS (40%), but
      not in healthy volunteers. Interestingly, no significant differences in frequency
      of well-known disease risk polymorphisms for aHUS were observed between healthy
      volunteers and aHUS patients. Our results suggested that although FH1 mutations
      relates to the development of Japanese aHUS in accordance with other ethnic
      studies, other factor may be required for factor H polymorphism to be a risk
      factor of Japanese aHUS.

PMID- 21868098
TI  - Clinical presentation of familial exudative vitreoretinopathy.
AB  - OBJECTIVE: To describe the clinical characteristics, staging and presentation of
      patients with familial exudative vitreoretinopathy (FEVR) in our clinical
      practice over the last 25 years. DESIGN: Case series, retrospective review.
      PARTICIPANTS: We included 273 eyes of 145 patients. METHODS: Data collected from
      charts included gender, gestational age at birth, birthweight, age at
      presentation, referring diagnosis, family history, prior ocular surgery, and
      clinical presentation in each eye. Eyes with invasive posterior segment
      procedures before initial presentation were excluded. MAIN OUTCOME MEASURES:
      Demographics on presentation and clinical staging. RESULTS: Patients were
      slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g
      4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at
      presentation of almost 6 years (range, <1 month-49 years). A positive family
      history of FEVR was obtained in 18% of patients. A positive family history for
      ocular disease consistent with but not diagnosed as FEVR was obtained in an
      additional 19%. Stage 1 FEVR was identified in 45 eyes, stage 2 in 33 eyes, stage
      3 in 42 eyes, stage 4 in 89 eyes, and stage 5 in 44 eyes. Radial retinal folds
      were seen in 77 eyes, 64 of which were temporal or inferotemporal in location.
      CONCLUSIONS: The FEVR patient population is remarkable for the wide range of age
      at presentation, gestational age, and birthweight. Although a positive family
      history on presentation may support the diagnosis of FEVR, a negative family
      history is of little help. The majority of retinal folds extended radially in the
      temporal quadrants, but radial folds were seen in almost all quadrants. Fellow
      eyes demonstrated a wide variation in symmetry. The presentation of FEVR may
      mimic the presentation of other pediatric and adult vitreoretinal disorders, and
      careful examination is often crucial in making the diagnosis of FEVR. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 21868099
TI  - Individual and relational contributions to parallel and joint attention in
      infancy.
AB  - OBJECTIVE: This study examined the contributions of maternal bids for joint
      attention, relationship quality, and infant characteristics, to individual
      differences in infants' parallel and joint attention. METHOD: Fifty-two 10-month
      olds and their mothers were assessed in order to investigate concurrent
      predictors of infant parallel attention, responding to joint attention, and
      initiating joint attention. RESULTS: Parallel attention was predicted by infants'
      higher mental development, low expression of negative emotionality, and maternal
      entertaining behaviors. Responding to joint attention was marginally predicted by
      total maternal bids for joint attention. Initiating joint attention was predicted
      by the infants' low expression of negative emotionality, as well as marginally
      predicted by fewer maternal teaching behaviors. CONCLUSION: These results further
      the understanding of the factors influencing infant parallel as well as joint
      attention.

PMID- 21868100
TI  - Mother and father adjustment during early parenthood: the roles of infant
      temperament and coparenting relationship quality.
AB  - We explored how parent gender, infant temperament, and coparenting dynamics
      worked together to shape mothers' and fathers' depressive symptoms, stress, and
      parental efficacy during early parenthood. We were interested in the coparenting
      relationship as a context that shapes how parents respond to their infant's
      temperamental qualities. Participants were 139 couples who had recently given
      birth to their first child. Parent reports of temperament were collected when the
      infant was 4-8 months old and reports of coparenting and parent adjustment were
      collected at 13 months. Two-level random intercept models revealed interactions
      between temperament and coparenting, highlighting the family system as a context
      for how men and women adapt to their parenting role. There was little evidence
      for mother-father differences in these associations.

PMID- 21868101
TI  - The need for chronic opioids to treat persistent noncancer pain.

PMID- 21868102
TI  - Prescription of opiate medications for chronic benign pain. Introduction.

PMID- 21868103
TI  - Quantitative and functional changes in peripheral natural killer cells in women
      with reproductive failure after artificial insemination with donor sperm.
AB  - Considerable evidence indicates that quantitative and/or functional abnormalities
      of natural killer (NK) cells are associated with reproductive failure. The
      objective of this study was to determine if peripheral NK percentage and activity
      are altered in women with reproductive failure after artificial insemination by
      donor (AID), and which parameters can best discriminate women with AID failure
      and normal controls. A case-control study of 20 fertile controls, 25 patients
      undergoing more than four treatment cycles without success (Group I), 25
      experiencing biochemical pregnancy loss (Group II), and 25 undergoing embryo
      growth arrest or miscarriage (Group III) was performed. The peripheral NK
      percentage and cytotoxicity was evaluated by flow cytometry. Our results showed
      that a significantly increased percentage of NK cell cytotoxicity (NKCC) was
      detected in all study groups compared with the controls. The percentage of
      CD56(+) NK cells was elevated in Groups II and III compared with the controls.
      The percentage of CD56(+)CD16(+) NK cells in the study groups was higher than
      that in the controls. By using receiver operating characteristic curve and
      logistic regression analysis, we found that NKCC combined with CD56(+)CD16(+) NK
      percentage had good predictive power. The overall predicted percentage correct
      was 0.89. These results suggest that enhanced NKCC and an elevated cytotoxic NK
      percentage may be associated with AID failure and can be biomarkers for
      predicting AID-induced failure.

PMID- 21868104
TI  - Clarifying the role of pain tolerance in suicidal capability.
AB  - Joiner's (2005) interpersonal-psychological theory of suicide hypothesizes that
      painful and provocative events increase pain tolerance. The theory further
      proposes that increased pain tolerance represents one component of increased
      suicidal capability. Although initial studies have been consistent with this
      model, several key aspects remain untested. In 67 undergraduates, we investigated
      associations among painful and provocative events, nonsuicidal self-injury,
      acquired capability for suicide, and pain tolerance, threshold, and perceived
      intensity. Results were highly consistent with the interpersonal-psychological
      theory: a multiple mediation model specified that pain tolerance - but not other
      pain variables - accounted for significant variance within the association
      between painful and provocative events and acquired capability for suicide. These
      results held even when the pain tolerance item was removed from the suicidal
      capability questionnaire. Results also supported the interpersonal-psychological
      theory hypothesis that nonsuicidal self-injury represents an important painful
      and provocative event that increases suicidal capability. Specifically,
      participants with a history of nonsuicidal self-injury displayed increased
      suicidal capability and decreased pain perception. Overall, these results
      indicate that pain tolerance plays an important and specific role in suicidal
      capability.

PMID- 21868105
TI  - Cognitive and affective empathy in depression linked to executive control.
AB  - Depression has been linked to executive dysfunction and emotion recognition
      impairments, associated with abnormalities in fronto-temporal and subcortical
      brain regions. Little is known about changes of different empathy subcomponents
      during depression, with potential impairments being related to the interpersonal
      difficulties of depressed patients. Twenty patients treated for an episode of
      unipolar depression and 20 matched healthy controls were assessed. Measures of
      dispositional and behavioural empathy components were administered along with
      tests of cognitive flexibility, response inhibition and working memory. Relative
      to controls, depressed patients showed higher self-reported dispositional empathy
      scores, mainly driven by increased personal distress scores. Patients and
      controls did not differ significantly in terms of behavioural cognitive empathy,
      empathic concern and personal affective involvement or in their executive
      function performance. In the patients, cognitive flexibility and response
      inhibition accuracy were associated with behavioural empathy. While an increased
      disposition towards feeling personal distress in response to other people's
      suffering seems to be in generally related to depressive symptoms, behavioural
      empathy might depend on the functional integrity of executive control during an
      episode of clinical depression. Impairments in this regard could contribute to
      the interpersonal difficulties depressed patients are frequently faced with which
      might have important implications for treatment.

PMID- 21868106
TI  - The Hebrew and the Arabic version of the LittlEARS(r) auditory questionnaire for
      the assessment of auditory development: results in normal hearing children and
      children with cochlear implants.
AB  - OBJECTIVE: With more children receiving cochlear implants at an early age, there
      is a need for evaluation and assessment of early auditory behavior. We present
      the translation of the LittlEARS(r) Auditory Questionnaire into Hebrew and into
      Arabic. First the validation of the LittlEARS(r) Auditory Questionnaire in normal
      hearing children was evaluated. Second, the auditory behavior and the progress in
      hearing skills of a group of children with cochlear implants were assessed.
      METHODS: A "back-translation" method was used to translate and adapt the
      LittlEARS(r) Auditory Questionnaire into Hebrew and into Arabic. Normal hearing
      participants included 70 Hebrew speaking and 97 Arabic speaking parents of
      children from 1 to 24 months of age with normal hearing. An additional group of
      42 parents of children with cochlear implants with a hearing age of up to 24
      months completed the LittlEARS(r) Auditory Questionnaire. 27 of them completed
      the questionnaire more than once at intervals, so that change and development
      could be recorded. Scores on the LittlEARS(r) Auditory Questionnaire were
      compared to results of SIR and CAP scales and other available auditory data.
      RESULTS: The results of the first study show that the curves found for the Hebrew
      and the Arabic translations of the LittlEARS(r) Auditory Questionnaire are
      essentially similar to those previously found for other languages. These curves
      reflect the age dependency of auditory skills. Furthermore, in the group with
      cochlear implants the developmental pattern was different than that of the normal
      hearing group, with an initial steep increase and a later slower improvement.
      This trend appeared both in curves of groups and in curves of individuals
      (individuals whose parents completed the questionnaire at several points in
      time). There was a high correlation between scores on the LittlEARS(r) Auditory
      Questionnaire and results of other audiologic tests, showing validity of results
      with the LittlEARS(r) Auditory Questionnaire. CONCLUSION: Both the Hebrew and
      Arabic versions of the LittlEARS(r) Auditory Questionnaire were found to be
      reliable and valid tools for assessment of the development of auditory behavior
      in children up to the age of 24 months. Furthermore, the LittlEARS(r) Auditory
      Questionnaire in both languages is useful in monitoring the progress of children
      with cochlear implant.

PMID- 21868107
TI  - Diagnostic and surgical challenge: middle ear dermoid cyst in 12 month old with
      branchio-oto-renal syndrome and multiple middle-ear congenital anomalies.
AB  - Described is the first case report, to our knowledge, of a middle-ear dermoid in
      a child with branchio-oto-renal (BOR) syndrome. Radiographic, pathologic, and
      intraoperative figures are shown. This was a diagnostic and surgical challenge as
      the presentation was similar to a congenital cholesteatoma and the child had
      numerous significant temporal bone abnormalities. After the intraoperative
      findings suggested a non-destructive process, the treatment strategy was altered.
      This case reiterates the need for a cautious, flexible operative approach in a
      syndromic child. Included is a relevant review of the literature and a detailed
      clinical analysis.

PMID- 21868108
TI  - De novo dominant mutation of GJB2 in two Chinese families with nonsyndromic
      hearing loss.
AB  - BACKGROUND: Mutations in the GJB2 gene are the most common cause of nonsyndromic
      autosomal recessive sensorineural hearing loss. A few mutations in GJB2 have also
      been reported to cause dominant nonsyndromic or syndromic hearing loss. However,
      de novo or dominant mutation in GJB2 is not common in Chinese populations.
      METHODS: Two probands with hearing impairment from unrelated Chinese families are
      reported here. Temporal CT scan, complete physical (including skin and hair) and
      otoscopic examinations, and an audiological study, including tympanometry,
      auditory brainstem response (ABR), auditory steady-state response (ASSR), and
      40Hz-auditory event-related potential (40 Hz-AERP), were carried out. The two
      exons of GJB2, the coding exons of SLC26A4, and mitochondrial 12S rRNA were
      sequenced. RESULTS: Sequencing of GJB2 in the two cases showed a heterozygous
      c.551G>A(p.R184Q) mutation, which was not found in other family members.
      Additionally, no other mutation in GJB2 was identified in the two family members.
      Paternity was confirmed by genotype analysis of 15 informative short tandem
      repeats (STRs) from the chromosomes. Sequence analysis of the coding exons of
      SLC26A4 and mitochondrial 12S rRNA was performed but no sequence aberration or
      deletion was found. CONCLUSIONS: A de novo GJB2 p.R184Q mutation can cause severe
      to-profound bilateral sensorineural hearing impairment. Although not common in
      Chinese patients with hearing loss, it is important to identify the specific
      phenotype and genotype correlations of the de novo dominant mutation in GJB2.

PMID- 21868109
TI  - Assessment of the use of hypolipidemic agents (HAs), mainly statins, in elderly
      subjects aged 80 years and more in Burgundy: analysis of 13,211 patients.
AB  - Only few studies have investigated the use of HA in elderly subjects and there
      are no data in very elderly subjects. We assessed the prescription of HA and
      analyzed the relationship between such prescriptions and frailty markers among
      persons aged 80 and more in an observational study. We recorded the prescriptions
      for 13,211 patients aged 80-109 years and affiliated to the "Mutualite-Sociale
      Agricole (MSA)" of Burgundy over a 1-month period. The prescription of a HA among
      all included patients, and the existence of serious long-term disease(s) (LTD),
      polypharmacy or a prescription of cardiovascular drugs among patients receiving a
      HA were recorder. Among the 13,211 patients, 3412 aged 80-98 years were treated
      with an HA. The main HA were statins (70.4%), and fibrates were used in 27.3% of
      cases. Of these 3412 patients, 2250 had one or several LTD mainly coronaropathy,
      hypertension, diabetes mellitus or peripheral artery disease. The mean number of
      drugs per prescription was 6.37. Among subjects treated with HA, 40% also
      received antiplatelets, 35.6% beta-blockers and 30% inhibitors of the renin
      angiotensin system. For 99% of the patients, the prescription of HA was a
      renewal. Prescribers were mainly general practitioners (96.8%). Statins are the
      most widely prescribed HA even among very elderly subjects. However, after 80
      years the prescription of HA, mainly statins, decreases with aging. This could be
      explained by polypathology, polypharmacy and the deterioration in metabolic
      functions which are markers of frailty. This study should encourage research into
      the use of statins in very elderly subjects.

PMID- 21868110
TI  - Physical activity (PA) and the disablement process: a 14-year follow-up study of
      older non-disabled women and men.
AB  - Few studies have explored the associations of reported PA (RPA) with the
      processes underlying the development of disability. The present study was
      performed to explore RPA among older persons and its association with onset of
      functional dependence and mortality. Among a probability sample of 1782 community
      living persons, aged 75-83 years, we evaluated the 1021 who reported no
      disability in basic activities of daily living. Participants were followed for a
      median of 8.34 years in public registers to determine onset of disability and
      mortality. RPA predicted mortality in older women (HR=1.77, 95%CI=1.42-2.19) and
      men (HR=1.65, 95%CI=1.27-2.14) over long time intervals. The effect of RPA
      persisted among permanently disabled older women, after adjusting for age,
      baseline vulnerability and grade of disability. Low RPA was independently
      associated with risk of incident disability (HR=1.56, 95%CI=1.10-2.23) in men.
      Among older women, the association between RPA and incidence of disability was
      attenuated in analyses that controlled for baseline mobility function. Thus, the
      association between physical activity and mortality reflected processes different
      from those underlying a simple relation between physical activity, disability and
      mortality. Physical activity was an ubiquitous predictor of longevity, but only
      for women.

PMID- 21868111
TI  - Nodular steatosis of the mitral valve.

PMID- 21868112
TI  - Stenosis of left ventricular outflow tract caused by severe kyphosis.

PMID- 21868113
TI  - Late calcification of the mitral-aortic junction causing transient complete atrio
      ventricular block after mediastinal radiation of Hodgkin lymphoma: multimodal
      visualization.

PMID- 21868114
TI  - A vanishing left ventricular thrombus: live imaging by trans-thoracic 2D
      echocardiography.

PMID- 21868115
TI  - Detrimental impact of socioeconomic status on exercise capacity in adults with
      congenital heart disease.
AB  - OBJECTIVES: To evaluate the relationship between socioeconomic status (SES),
      access to physical activity resources, urban-rural dwelling, levels of pollution
      and exercise capacity in adult congenital heart disease (ACHD) patients.
      BACKGROUND: Exercise intolerance is prevalent in ACHD and the contributing
      factors are poorly understood. METHODS: A total of 1268 ACHD patients living in
      England who underwent cardiopulmonary exercise testing at our center were
      included. Neighborhood deprivation (English Indices of Deprivation), urban-rural
      dwelling, availability of green space, distance to the closest gym/fitness center
      and levels of pollution were estimated based on administrative data. RESULTS:
      Urban-rural dwelling, availability of green space and levels of pollution were
      unrelated to exercise capacity. Lower SES was associated with a significantly
      lower peak oxygen consumption (P<0.002) and heart rate reserve (P<0.004). This
      association was non-linear and most pronounced in ACHD patients with cardiac
      defects of medium complexity living in the most socioeconomically disadvantaged
      communities. Low SES was associated with higher prevalence of diabetes (P=0.015)
      and smoking (P=0.01). Coronary artery disease was rare in this young population
      and low SES was found to be related to exercise capacity independently of the
      presence of coronary artery disease. CONCLUSIONS: Living in poorer areas is
      associated with exercise intolerance in contemporary ACHD patients. Although low
      SES is linked to traditional cardiovascular risk factors, the deleterious effects
      of SES on exercise capacity seem to be only partially mediated via coronary
      artery disease. Reducing social inequalities in ACHD patients may have a positive
      effect on quality of life and long-term prognostic implications.

PMID- 21868116
TI  - A common first-order time-to-contact based control of hand-closure initiation in
      catching and grasping.
AB  - To catch or grasp an object, the initiation of hand closure has to be coordinated
      with the relative movement between hand and object. In search of a common control
      of the initiation of hand closure for both tasks (van de Kamp, Bongers, & Zaal,
      2010), the authors studied two tasks, catching while keeping the hand stationary
      and prehension. They showed that the initiation of hand closure could well be
      based on first-order time-to-contact in the prehension task but not in the
      catching task studied. The current study tested if the fact that the hand-object
      gap was closed at a linear rate made that the initiation of hand closure could
      not be explained on the basis of that same first-order time-to-contact in the
      catching task. In Experiment 1, the participants had to catch targets that
      approached at nonlinear rates while keeping the hand stationary. In Experiment 2,
      the participants were free to move their hand in catching the approaching
      objects, allowing the closure of the hand-object gap to occur at a nonlinear rate
      as it would in natural movements. The results showed that the first-order time-to
      contact based control of the initiation of hand closure did apply in Experiment
      2, whereas it did not in Experiment 1. It was concluded that constraining the
      catching task such that it became unfamiliar led to a hampered timing, thus
      obstructing the finding of the common control in the previous study, and in
      Experiment 1 of the current study.

PMID- 21868117
TI  - Mutations of beta-tubulin codon 198 or 200 indicate thiabendazole resistance
      among isolates of Penicillium digitatum collected from citrus in Taiwan.
AB  - Penicillium digitatum causes green mold on citrus, resulting in severe
      postharvest fruit decay and economic losses in many citrus-producing areas of the
      world. Forty isolates of P. digitatum were cultured from citrus groves,
      packinghouses, and local markets in Taiwan, and assessed quantitatively for their
      sensitivity to thiabendazole (TBZ) fungicide. Sensitivity assays using a 96-well
      microtiter plate revealed that, of 40 isolates examined, only one isolate
      collected from fruit produced in Taiwan and two isolates from Florida-imported
      citrus fruit were sensitive to TBZ. The concentration of TBZ causing a 50% growth
      reduction (EC(50)) was less than 1 MUg/mL. The remaining 37 isolates could
      tolerate high concentrations of TBZ, with an EC(50) greater than 80 MUg/mL.
      Overall, more than 97% of P. digitatum isolates tested in Taiwan were found to be
      resistant to TBZ. In vitro assays also revealed the ineffectiveness of TBZ for
      controlling a TBZ-resistant isolate on sweet oranges. A sequence analysis of beta
      tubulin genes revealed that all TBZ-resistant isolates displayed a single
      transversion point mutation, resulting in a change at either amino acid 198
      (glutamic acid->glutamine) or 200 (phenylalanine->tyrosine). The repetitive use
      of a single fungicide over several decades has favored the selection and
      dominance of TBZ-resistant isolates of P. digitatum.

PMID- 21868118
TI  - Molecular approaches to analysing the microbial composition of raw milk and raw
      milk cheese.
AB  - The availability and application of culture-independent tools that enable a
      detailed investigation of the microbiota and microbial biodiversity of food
      systems has had a major impact on food microbiology. This review focuses on the
      application of DNA-based technologies, such as denaturing gradient gel
      electrophoresis (DGGE), temporal temperature gradient gel electrophoresis (TTGE),
      single stranded conformation polymorphisms (SSCP), the polymerase chain reaction
      (PCR) and others, to investigate the diversity, dynamics and identity of microbes
      in dairy products from raw milk. Here, we will highlight the benefits associated
      with culture-independent methods which include enhanced sensitivity, rapidity and
      the detection of microorganisms not previously associated with such products.

PMID- 21868119
TI  - Anisakis simplex s.l. parasitization in mackerel (Scomber japonicus) caught in
      the North of Morocco--prevalence and analysis of risk factors.
AB  - Consumption of mackerel (Scomber japonicus) is very widespread in Morocco, where
      its production is an important economic pillar. We investigated the prevalence of
      infection by Anisakis spp. in mackerel caught in Moroccan waters, analyzing
      infection risk factors. The prevalence was generally higher in fish from the
      Atlantic (67.9%) than from the Mediterranean (57.0%), but they did not differ in
      the mean abundance, intensity, or prevalence of muscle parasitization. A.
      pegreffii was the predominant species (82.6% of larvae) followed by the hybrid A.
      simplex s.s./A. pegreffii (16.3%). Only one L3 of A. simplex s.s. was found in a
      specimen of S. japonicus from the Atlantic. Mackerel infection was associated
      with total fish weight, gonad weight, catch area, and catch season. However,
      muscle infection was associated solely with total weight and parasite loads. The
      consumption of lower-weight mackerel may be a good prophylactic measure against
      human anisakiasis.

PMID- 21868120
TI  - Assisted reproductive technologies: a systematic review of safety and
      effectiveness to inform disinvestment policy.
AB  - OBJECTIVE: Health policy relating to assisted reproductive technologies (ART) has
      been variably informed by clinical evidence, social values, political and fiscal
      considerations. This systematic review examined key factors associated with
      specific benefits and harms of ART to inform the development of a model for
      generating policy recommendations within an Australian disinvestment research
      agenda. METHODS: Six databases were searched from 1994 to 2009. Included articles
      contained data on safety and/or effectiveness of in vitro fertilisation (IVF) or
      IVF with intracytoplasmic sperm injection with reference to female age, male age
      or cycle rank. Narrative descriptions of key outcomes (live birth, miscarriage)
      were constructed alongside tabular summaries. RESULTS: Sixty-eight studies and
      one registry report were included. There was substantial heterogeneity present
      within the evidence-base which limited the strength and scope of conclusions that
      could be drawn. However, this review does affirm the differential effectiveness
      associated with the ageing of ART patients with regard to live birth and
      miscarriage. CONCLUSION: From the available evidence, it was not possible to
      determine an explicit age or cycle rank that could be used to formulate
      defensible policy responsive to identified differential effectiveness.
      Stakeholder interpretation of this evidence-base may assist in developing policy
      that can incorporate uncertainty and reflect social values.

PMID- 21868121
TI  - Australian Aboriginal and Torres Strait Islander communities and the development
      of pandemic influenza containment strategies: community voices and community
      control.
AB  - OBJECTIVES: To develop culturally appropriate and effective strategies to reduce
      the risk from pandemic influenza (H1N109) in rural and remote Australian
      Aboriginal and Torres Strait Islander communities. METHODS: Participatory Action
      Research (PAR) approach that enabled communities and researchers to work together
      to develop understanding and take action to reduce risk. RESULTS: The H1N109
      pandemic raised deep concerns and serious issues in all of the Aboriginal and
      Torres Strait Islander communities involved in this project. The participants
      expressed distrust and scepticism in relation to current Australian health
      policies on containment and told the researchers that specific plans for
      Aboriginal and Torres Strait Islander peoples were needed. Respondents indicated
      that policies and plans had been developed without respectful engagement with
      communities. The strong and recurring themes that emerged from the PAR cycles
      were: the importance of family; ways of life and realities of living in response
      to influenza; and key messages to government and health services to focus on
      communication, understanding and respect. CONCLUSION: The essential work of
      reducing risk of pandemic influenza with Aboriginal and Torres Strait Islander
      communities is not straightforward, but this project has highlighted a number of
      useful pathways to continue to journey along with communities. A number of
      strategies to reduce the spread of pandemic influenza in Aboriginal and Torres
      Strait Islander communities were identified. These strategies would make a good
      starting point for conversations with communities and health services. In
      Aboriginal and Torres Strait Islander communities the environment, community
      structures and traditions vary. Respectful engagement with communities is needed
      to develop effective policy.

PMID- 21868122
TI  - Off to a slow start: under-development of the complement system in term newborns
      is more substantial following premature birth.
AB  - Complement represents a keystone to the innate immune system, with three
      activation pathways that utilise foreign microbial pattern recognition as well as
      activation by the host's specific antibodies. However, innate immunity is not
      synonymous with neonatal immunity. The complement system in healthy term (38-42
      weeks gestation) newborns is under-developed and, with only a few exceptions
      (e.g. C7 and factor D), the circulating complement component concentrations are
      between 10 and 80% of adult levels. Complement activation is tightly regulated
      and the circulating regulator levels are also low relative to adults, sometimes
      at almost undetectable levels (e.g. C4b-binding protein). For premature newborns,
      these relative deficiencies are even more marked. Newborns are known to be more
      susceptible to infection, and the importance of complement, not only through its
      decreased ability to directly lyse bacteria with the common terminal pathway, but
      also its reduced ability to recruit (chemotaxis) innate and adaptive leukocytes
      to sites of microbial invasion and reduced ability to enhance phagocytosis
      (opsonisation) will be discussed. Complement also holds a key role in enhancing
      and directing refinement of the specific antibody response to pathogens (as an
      adjuvant) that likely plays a role in the well-known under-performance of the
      humoral immune response in newborns.

PMID- 21868123
TI  - Age-related macular degeneration and the complement system.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      developed world. It is a complex multifactorial disease, and despite new advances
      in treatment, many patients still succumb to visual impairment. The complement
      pathway has been implicated in the pathogenesis of many diseases, and recently
      variants in several genes encoding complement pathway proteins have been
      associated with AMD. Complement proteins have been found in histological
      specimens of eyes with AMD. Altered levels of both intrinsic complement proteins
      and activated products have been found in the circulation of patients with AMD.
      Complement activation may be triggered by oxidative stress, resulting from
      retinal exposure to incoming light; indeed an inter-play between these two
      pathological processes seems to exist. Finally, complement inhibitors are
      currently being evaluated in clinical trials. This article reviews the role of
      the complement system in AMD, and the potential of complement inhibition in
      preventing the devastating blindness resulting from this disease.

PMID- 21868124
TI  - Role and regulation of autophagy in the development of acinar structures formed
      by bovine BME-UV1 mammary epithelial cells.
AB  - Autophagy is a catabolic process providing an alternative energy source for cells
      under stressful conditions such as starvation, growth factor deprivation or
      hypoxia. During involution of the bovine mammary gland autophagy is induced in
      mammary epithelial cells (MECs) as a survival mechanism, and is tightly regulated
      by hormones and growth factors necessary for gland development. In the present
      study we adapted the three-dimensional culture model to investigate the role of
      autophagy during formation of alveoli-like structures by bovine BME-UV1 MECs
      grown on extracellular matrix (ECM) components. Using confocal microscopy and
      Western-blot analyses of autophagic and apoptotic markers: LC3, and cleaved
      caspase-3, we showed that autophagy was induced in centrally localized cells
      within the developing acini. These cells lacked a direct contact with ECM, and
      formed a distinct population from the outer layer of cells. Induction of
      autophagy preceded apoptosis, but did not inhibit the formation of a hollow
      lumen. In the presence of steroid hormones: 17beta-estradiol and progesterone,
      although autophagy was augmented, acini formation proceeded normally. In
      contrast, the major lactogenic hormone: prolactin, which supports functional
      differentiation of alveoli, did not alter induction of autophagy within the
      spheroids. BME-UV1 cells cultured on Matrigel in the presence of growth factors
      IGF-I and EGF formed larger, underdeveloped acini without lumens due to caspase-3
      inhibition, and sustained autophagy in the centre of the spheroids, while TGF
      beta1 accelerated apoptosis, and increased autophagy significantly. Our
      observations suggest that sex steroids 17beta-estradiol and progesterone, as well
      as growth factor TGF-beta1 may regulate the development of the bovine mammary
      gland by inducing autophagy in addition to regulating proliferation and apoptosis
      of MECs. These data indicate that autophagy may play an important role during
      alveolargenesis.

PMID- 21868126
TI  - A look at tricellulin and its role in tight junction formation and maintenance.
AB  - Tight junctions are elaborate networks of transmembrane and cytosolic proteins
      that regulate epithelial permeability. Tricellulin was the first tight junction
      protein found at tricellular tight junctions, the specialized structures
      occurring where three cells meet together. Here, we summarize the current
      knowledge about tricellulin (marvelD2), a MARVEL domain protein. We address
      tricellulin location at tricellular junctions, and establish the comparison with
      the other members of the MARVEL family, occludin (marvelD1) and marvelD3. The
      structure of tricellulin and its membrane folding, as well as the proposed
      molecular interactions of tricellulin with other tight junction proteins,
      together with the interplay between those proteins are also discussed. In
      addition, we address the role of tricellulin in barrier properties,
      discriminating the involvement of the protein in paracellular permeability at
      bicellular and at tricellular tight junctions. Moreover, the key importance of
      the protein for hearing is highlighted based on the fact that mutations in TRIC,
      the human tricellulin gene, lead to deafness. Furthermore, this review points to
      some of the aspects that still deserve clarification for a better understanding
      of the biology of tight junctions in general and of tricellulin in particular.

PMID- 21868125
TI  - Yeast ubiquitin ligase Rsp5 contains nuclear localization and export signals.
AB  - The Rsp5 ubiquitin ligase regulates numerous cellular processes. Rsp5 is mainly
      localized to the cytoplasm but nuclear localization was also reported. A
      potential nuclear export signal was tested for activity by using a GFP(2)
      reporter. The 687-LIGGIAEIDI-696 sequence located in the Hect domain was
      identified as a nuclear export signal active in a Crm1-dependent manner, and its
      importance for the localization of Rsp5 was documented by using fluorescence
      microscopy and a lacZ-based reporter system. Analysis of the cellular location of
      other Rsp5 fragments fused with GFP(2) indicated two independent potential
      nuclear localization signals, both located in the Hect domain. We also uncovered
      Rsp5 fragments that are important to targeting/tethering Rsp5 to various regions
      in the cytoplasm. The presented data indicate that Rsp5 ligase is a shuttling
      protein whose distribution within the cytoplasm and partitioning between
      cytoplasmic and nuclear locations is determined by a balance between the actions
      of several targeting sequences and domains.

PMID- 21868127
TI  - Guidelines of care for the management of primary cutaneous melanoma. American
      Academy of Dermatology.
AB  - The incidence of primary cutaneous melanoma has been increasing dramatically for
      several decades. Melanoma accounts for the majority of skin cancer-related
      deaths, but treatment is nearly always curative with early detection of disease.
      In this update of the guidelines of care, we will discuss the treatment of
      patients with primary cutaneous melanoma. We will discuss biopsy techniques of a
      lesion clinically suspicious for melanoma and offer recommendations for the
      histopathologic interpretation of cutaneous melanoma. We will offer
      recommendations for the use of laboratory and imaging tests in the initial workup
      of patients with newly diagnosed melanoma and for follow-up of asymptomatic
      patients. With regard to treatment of primary cutaneous melanoma, we will provide
      recommendations for surgical margins and briefly discuss nonsurgical treatments.
      Finally, we will discuss the value and limitations of sentinel lymph node biopsy
      and offer recommendations for its use in patients with primary cutaneous
      melanoma.

PMID- 21868128
TI  - Data linkage between existing healthcare databases to support hospital
      epidemiology.
AB  - Enhancing the use of existing datasets within acute hospitals will greatly
      facilitate hospital epidemiology, surveillance, the monitoring of a variety of
      processes, outcomes and risk factors, and the provision of alert systems.
      Multiple overlapping data systems exist within National Health Service (NHS)
      hospitals in the UK, and many duplicate data recordings take place because of the
      lack of linkage and interfaces. This results in hospital-collected data not being
      used efficiently. The objective was to create an inventory of all existing
      systems, including administrative, management, human resources, microbiology,
      patient care and other platforms, to describe the data architecture that could
      contribute valuable information for a hospital epidemiology unit. These datasets
      were investigated as to how they could be used to generate surveillance data, key
      performance indicators and risk information that could be shared at board,
      clinical programme group, specialty and ward level. An example of an output of
      this integrated data platform and its application in influenza resilience
      planning and responsiveness is described. The development of metrics for staff
      absence and staffing levels may also be used as key indicators for risk
      monitoring for infection prevention. This work demonstrates the value of such a
      data inventory and linkage and the importance of more sophisticated uses of
      existing NHS data, and innovative collaborative approaches to support clinical
      care, quality improvement, surveillance, emergency planning and research.

PMID- 21868129
TI  - A field test of time-based emergency department quality measures.
AB  - STUDY OBJECTIVE: We examine practical aspects of collecting time-based emergency
      department (ED) performance measures. METHODS: Seven measures were implemented in
      6 hospitals during 1 year. Structured interviews were used to assess the benefits
      and burdens of reporting. In 2 hospitals, Centers for Medicare & Medicaid
      Services (CMS) sample size requirements for 3 measures were compared to a
      reasonable sample size estimate (in which 95% of samples fell within 15 minutes
      of the population median). RESULTS: ED performance data on 29,587 admitted
      patients and 127,467 discharged patients were reported. Median throughput time
      for admitted patients ranged from 327 to 663 minutes and for discharged patients
      ranged from 143 to 311 minutes. Other performance measures varied similarly (2-
      to 3-fold between hospitals). In general, ED throughput was longer at academic
      sites and those with higher volume. Several benefits of reporting were
      identified, including promoting ED quality improvement, accountability, and
      practice standardization. The burdens included having to access multiple
      information technology systems and difficulties setting up the data collection.
      Most respondents found great value in the throughput measures and time to pain
      medication but less value in time to chest radiograph. The human capital required
      to implement measures varied by hospital and staff demonstrated a learning curve.
      Our empirically derived minimum reliable sample sizes were different from CMS
      recommendations. CONCLUSION: There is great variation in performance between EDs
      in time-based ED measures. There are multiple reporting benefits. Reporting
      burdens seemed to lessen after data systems were established. The CMS sample size
      requirements for throughput measures may not be optimal compared with actual ED
      throughput data.

PMID- 21868130
TI  - Public health worker attitudes and beliefs concerning 2009 H1N1 and seasonal
      influenza vaccines.
AB  - In this study examining public health workers' 2009 H1N1 and seasonal influenza
      vaccination uptake, a survey was conducted to assess flu vaccine acceptance, as
      well as behaviors and beliefs regarding acceptance, among public health workers
      in southeastern Tennessee. Factors found to be significantly associated with
      acceptance of the 2009 H1N1 vaccine were direct patient care, previous flu
      vaccination, vaccine safety concerns, and receipt of seasonal flu vaccine.

PMID- 21868131
TI  - Rapid control of a scabies outbreak at a tertiary care hospital without ward
      closure.
AB  - BACKGROUND: Although scabies outbreaks in hospitals are frequent, the optimal
      approach to management of these outbreaks has not yet been defined. We describe a
      hospital scabies outbreak that was successfully controlled without ward closure.
      METHODS: An outbreak of scabies at a teaching hospital and subsequent control
      measures were investigated. Outcomes included the number of cases affecting
      patients and staff, number of patients and staff requiring prophylaxis, duration
      of the outbreak, and cost of the outbreak. Outcomes were compared with those in a
      similar outbreak occurring at the same hospital 20 years earlier and with other
      published descriptions of hospital scabies outbreaks. RESULTS: In January 2010, a
      patient who had undergone renal transplantation was admitted 3 times to St.
      Michael's Hospital, but a diagnosis of scabies was not considered until the final
      admission. Widespread exposure of patients and staff on 2 wards prompted the
      establishment of an outbreak management team. Initial interventions focused on
      isolation and treatment of the index case and on contact tracing to identify and
      treat secondary cases and to offer prophylaxis to direct contacts. Five
      symptomatic staff members and 2 patient cases were quickly identified, an
      outbreak was declared, and mass simultaneous prophylaxis was initiated on the 2
      involved wards. A single case occurred 2 weeks after the mass prophylaxis program
      in a staff member who had not received the prophylaxis. Six weeks after the onset
      of symptoms, the end of the outbreak was declared. No additional cases have been
      reported up to the time of publication. The total cost of the outbreak was
      $20,000. CONCLUSIONS: Early recognition of crusted scabies is essential to
      prevent outbreaks. Once an outbreak occurs, prompt control of the index patient
      and rapid tracing of contacts to identify secondary cases are necessary. When
      prolonged exposure to a case of crusted scabies results in multiple secondary
      cases, institution of simultaneous mass prophylaxis is the most efficient
      strategy for terminating the outbreak and can be implemented without ward
      closure.

PMID- 21868132
TI  - Guide to the elimination of orthopedic surgery surgical site infections: an
      executive summary of the Association for Professionals in Infection Control and
      Epidemiology elimination guide.
AB  - This article is an executive summary of the APIC Guide to the Elimination of
      Orthopedic Surgical Site Infections. Infection preventionists, care providers,
      and perioperative personnel are encouraged to obtain the original, full length
      APIC Elimination Guide for more thorough coverage on strategies to prevent
      surgical site infections in orthopedic surgery.

PMID- 21868133
TI  - Introducing a population-based outcome measure to evaluate the effect of
      interventions to reduce catheter-associated urinary tract infection.
AB  - BACKGROUND: The catheter-associated urinary tract infection (CAUTI) measure
      recommended by the National Healthcare Safety Network (NHSN) accounts for the
      risk of infection in patients with an indwelling urinary catheter, but might not
      adequately reflect all efforts aimed to enhance patient safety by reducing
      urinary catheter use. METHODS: We used computer-based Monte Carlo simulation to
      compare the NHSN-recommended CAUTI rate (CAUTIs per 1,000 catheter-days) with the
      proposed "population CAUTI rate" (CAUTIs per 10,000 patient-days). We simulated
      100 interventions with a wide range of effects on catheter utilization and CAUTI
      risk in patients with catheters, and then compared the 2 measures before and
      after intervention across the simulated interventions. RESULTS: Out of our 100
      simulated interventions, 93 yielded reductions in CAUTI; however, in 25 (27%) of
      these 93 simulations, the NHSN CAUTI rate increased after the intervention. In
      addition, among the 68 simulations in which both the NHSN and the population
      CAUTI rates decreased, the percent decreases in the population CAUTI rate were
      consistently greater than those in the NHSN rate. CONCLUSION: The population
      CAUTI rate-CAUTIs per 10,000 patient-days-should be calculated along with the
      NHSN rate, particularly in settings where interventions lead to substantial
      reductions in catheter placement. We suspect that this population CAUTI rate may
      eventually emerge as a primary outcome for hospital-based quality improvement
      interventions for reducing urinary catheter utilization, especially those
      focusing on avoiding urinary catheter placement.

PMID- 21868134
TI  - 2009-2010 novel influenza A (H1N1) vaccination coverage in the Republic of Korea.
AB  - This study aimed to assess vaccination coverage for novel influenza A (H1N1) in
      Korea using a immunization registry system as the data source. Vaccination
      coverage was found to be 26.1% for the total population and 54.4% for priority
      groups targeted by a national vaccination campaign between October 27, 2009, to
      March 31, 2010. The factors associated with increased coverage were rapid
      vaccination and free vaccination; these factors may need to be considered in
      future pandemics.

PMID- 21868135
TI  - No association of MTHFR c.677C>T variant with sporadic ALS in an Italian
      population.
AB  - The c.677C>T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene
      (MTHFR) has been recently associated with susceptibility to sporadic amyotrophic
      lateral sclerosis (ALS). We have investigated this association in 450 ALS
      patients and 700 control subjects from Italy. No significant association was
      observed at the genotype and allelic level, either for the c.677C>T variant alone
      or in combination with PON1 polymorphisms. Our negative results suggest that the
      MTHFR c.677C>T polymorphism is not a risk factor for ALS in the Italian
      population.

PMID- 21868136
TI  - Synthesis, evaluation and application of polycyclic fluorescent analogues as N
      methyl-D-aspartate receptor and voltage gated calcium channel ligands.
AB  - A series of polycyclic fluorescent ligands were synthesised and evaluated in
      murine striatal synaptoneurosomes for N-methyl-D-aspartate receptor (NMDAR)
      mediated calcium flux inhibition and inhibition of calcium influx through voltage
      gated calcium channels (VGCC). Amantadine (a) and N-(1-adamantyl)-1,3
      propanediamine (c) substituted with 1-cyanoisoindole (3), indazole (5),
      dinitrobenzene (7, 8), dansyl (9, 10) and coumarin (11) moieties showed moderate
      to high inhibition of the NMDAR. A high degree of VGCC inhibition was observed
      for the cyanoisoindole compounds (3, 4) the dansyl compounds (9, 10) and the
      coumarin compound (12). Fluorophores conjugated to hydroxy-4-aza-8
      oxoheptacyclotetradecane (13, 14) did not exhibit any significant VGCC
      inhibition, but the indazole conjugate (14) showed promising NMDAR activity. Dose
      response curves were calculated for selected NMDAR inhibitors (8-11) and N-[3-(1
      adamantylamino)propyl]-5-dimethylaminonaphthalene-1-sulfonamide (10) exhibited
      the highest activity of the novel compounds. Compound 10 was further used as a
      fluorescent NMDAR ligand in a fluorescent competition assay utilizing MK-801,
      NGP1-01 and amantadine as known NMDAR inhibitors to demonstrate the possible
      applications of the novel fluorescent compounds. These small molecule fluorescent
      ligands can be considered as possible pharmacological tools in assay development
      and/or other investigations in the study of neurodegeneration.

PMID- 21868137
TI  - Pyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene
      biosynthesis in human neutrophils.
AB  - We recently presented that compounds 4a-b moderately inhibited leukotriene (LT)
      formation in human neutrophils. For structural derivatization of 4a-b, novel
      thirty-six title compounds were synthesized and led to more potent inhibition of
      LT biosynthesis in activated human neutrophils exemplified by compounds 15, 27
      30, 32-37, 41, 42 with IC(50) values in the range of 1.6-3.5 MUM. Moreover,
      compounds 32, 35, 42, 43 and 44 showed a substantial inhibition of platelet COX-1
      activity with IC(50) of 2.5, 0.041, 0.3, 0.9 and 0.014 MUM, respectively, leading
      up to dual acting inhibitors. On the basis of their high potency in cellular
      environment, these straightforward pyrazole-3-propanoic acid derivatives may
      possess potential in the design of more potent compounds for intervention with
      inflammatory and allergic diseases.

PMID- 21868138
TI  - Synthesis and characterization of novel PUFA esters exhibiting potential
      anticancer activities: an in vitro study.
AB  - Polyunsaturated fatty acids (PUFAs) have been reported to play a regulatory role
      in tumour growth progression. In the present study, we have synthesized ester
      derivatives of two important PUFA viz., linoleic acid (LA) and arachidonic acid
      (AA) with propofol, a widely used general anaesthetic-sedative agent. The novel
      propofol ester analogues have been found to inhibit various cancer cell lines in
      a dose-dependent manner. Moreover, the compounds have been found to induce
      apoptotic cell death by enhancing the release of cytochrome c and expression of
      caspase-3. The data of the present study suggest that novel propofol-PUFA esters
      have strong potential to emerge as effective anticancer agents.

PMID- 21868139
TI  - Effects of repeated exposure on acceptance of initially disliked and liked Nordic
      snack bars in 9-11 year-old children.
AB  - BACKGROUND & AIMS: Children's food choices are guided by their preferences. It is
      established, however, that repeated exposure to a novel food increases children's
      acceptance. This study investigated how acceptance of an initially liked and
      disliked snack bar develops in 9-11 year-old children. METHODS: 315 children were
      randomised into three groups: A control group (n = 111) and two groups exposed to
      an initially liked kamut bar (n = 94) and an initially disliked sea buckthorn bar
      (n = 110). Acceptance of both bars was tested before and after the exposure
      period, and on the 9th exposure. RESULTS: Intake of both bars increased
      significantly in the exposure groups. There was no difference in the control
      groups' intake or liking of the bars between pre and post-testing. Liking rose
      significantly for children exposed to the disliked sea buckthorn bar, while this
      was not observed in children exposed to the liked kamut bar. In a post-test
      children exposed to kamut bars had higher intake of that bar than non-exposed
      children. This was also observed for the sea buckthorn bar that was also given
      significantly higher liking scores by the exposure group. CONCLUSIONS: The
      majority of children exposed to an initially disliked bar increase acceptance
      after nine exposures to the same level as an initially liked bar. Children
      repeatedly exposed to a liked bar show stable acceptance.

PMID- 21868140
TI  - Breakfast cereals and risk of hypertension in the Physicians' Health Study I.
AB  - BACKGROUND & AIMS: Hypertension is a major public health problem. While many
      dietary factors affect the risk of developing hypertension, limited data are
      available on the association between consumption of breakfast cereal and incident
      hypertension. We examined the association between breakfast cereal consumption
      and the risk of hypertension. METHODS: We prospectively analyzed data from 13,368
      male participants of the Physicians' Health Study I. Consumption of breakfast
      cereals was estimated using an abbreviated food frequency questionnaire and
      incident hypertension was ascertained through yearly follow-up questionnaires.
      RESULTS: The average age of study participants was 52.4 +/- 8.9 years (range 39.7
      85.9) during the initial assessment of cereal intake (1981-1983). During a mean
      follow up of 16.3 years, 7267 cases of hypertension occurred. The crude incidence
      rates of hypertension were 36.7, 34.0, 31.7, and 29.6 cases/1000 person-years for
      people reporting breakfast cereal intake of 0, <=1, 2-6, and >=7 servings/week,
      respectively. In a Cox regression model adjusting for age, smoking, body mass
      index, alcohol consumption, fruit and vegetable consumption, physical activity,
      and history of diabetes mellitus, hazard ratios (95% CI) for hypertension were
      1.0 (reference), 0.93 (0.88-0.99), 0.88 (0.83-0.94), and 0.81 (0.75-0.86) from
      the lowest to the highest category of cereal consumption, respectively (p for
      trend <0.0001). This association was strongest for whole grain cereals and was
      observed in lean as well as overweight or obese participants. CONCLUSIONS: The
      results of this longitudinal cohort study suggest that whole grain breakfast
      cereal consumption confers a lower risk of hypertension in middle-aged adult
      males.

PMID- 21868141
TI  - Soil to leaf transfer factor for the radionuclides 226Ra, 40K, 137Cs and 90Sr at
      Kaiga region, India.
AB  - Transfer factors are the most important parameters required for mathematical
      modeling used for environmental impact assessment of radioactive contamination in
      the environment. In this paper soil to leaf transfer factor for the radionuclides
      40K, 226Ra, 137Cs and 90Sr is estimated for Kaiga region in Karnataka state,
      India. Among the plants in which study is carried out, 226Ra, 40K, 137Cs and 90Sr
      activity in leaves of herbaceous plants is higher than that of tree leaves. Soil
      to leaf transfer factor for 226Ra, 40K, 137Cs and 90Sr was found to be in the
      range of 0.03-0.65, 0.32-8.04, 0.05-3.03 and 0.42-2.67 respectively.

PMID- 21868142
TI  - Screening of Cd tolerant genotypes and isolation of metallothionein genes in
      alfalfa (Medicago sativa L.).
AB  - In order to evaluate Cd tolerance in wide-ranging sources of alfalfa (Medicago
      sativa) and to identify Cd tolerant genotypes which may potentially be useful for
      restoring Cd-contaminated environments, thirty-six accessions of alfalfa were
      screened under hydroponic culture. Our results showed that the relative root
      growth rate varied from 0.48 to 1.0, which indicated that different alfalfa
      accessions had various responses to Cd stress. The candidate fragments derived
      from differentially expressed metallothionein (MT) genes were cloned from leaves
      of two Cd tolerant genotypes, YE and LZ. DNA sequence and the deduced protein
      sequence showed that MsMT2a and MsMT2b had high similarity to those in leguminous
      plants. DDRT-PCR analysis showed that MsMT2a expressed in both YE and LZ plants
      under control and Cd stress treatment, but MsMT2b only expressed under Cd stress
      treatment. This suggested that MsMT2a was universally expressed in leaves of
      alfalfa but expression of MsMT2b was Cadmium (Cd) inducible.

PMID- 21868143
TI  - Podocyte disorders: Core Curriculum 2011.

PMID- 21868144
TI  - Towards a sociology of diagnosis: reflections and opportunities.

PMID- 21868145
TI  - Molecular dynamics simulations of T-20 HIV fusion inhibitor interacting with
      model membranes.
AB  - T-20 (also known as enfuvirtide) is a fusion inhibitor peptide known to have some
      effectiveness in the control of progression of HIV infection by inhibiting the
      fusion of the HIV envelope with the target cell membrane. Recent results indicate
      that T-20 is able to interact with membranes in the liquid disordered state but
      not with membranes in an ordered state, which could be linked to its
      effectiveness. A detailed molecular picture of the interaction of these molecules
      with membranes is still lacking. To this effect, extensive molecular dynamics
      simulations (100 ns) were carried out to investigate the interaction between T-20
      and bilayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and
      POPC/cholesterol (1:1). Membrane properties such as area/lipid, density profiles,
      order parameters and membrane thickness were studied. It was observed that T-20
      has the ability to interact to different extents with both model membranes in
      this study and that peptide interaction with the bilayer surface has a local
      effect on membrane structure. The formation of hydrogen bonding between certain
      peptide residues and the POPC phosphate group was observed. However, T-20 showed
      a more limited extent of interaction with model membranes when compared with
      other, more efficient, peptides (such as T-1249). This effect is most notable in
      POPC/Chol membranes in which interaction is especially weak, owing to less
      peptide residues acting as H bond donors to POPC and virtually no H bonds being
      formed between T-20 and cholesterol. This lower ability to interact with
      membranes is probably correlated with its smaller inhibitory efficiency.

PMID- 21868146
TI  - Isolation and characterization of aerobic culturable arsenic-resistant bacteria
      from surfacewater and groundwater of Rautahat District, Nepal.
AB  - Arsenic (As) contamination of groundwater is a serious Environmental Health
      Management issue of drinking water sources especially in Terai region of Nepal.
      Many studies have reported that due to natural abundance of arsenic in the
      environment, various bacteria have developed different resistance mechanisms for
      arsenic compound. In this study, the culturable arsenic-resistant bacteria
      indigenous to surfacewater as well as groundwater from Rautahat District of Nepal
      were randomly isolated by standard plate count method on the basis of viable
      growth on plate count agar amended with arsenate ranging from 0, 0.5, 10, 40, 80
      to 160 milligram per liter (mg/l). With respect to the morphological and
      biochemical tests, nine morphologically distinct potent arsenate tolerant
      bacteria showed relatedness with Micrococcus varians, Micrococcus roseus,
      Micrococcus luteus, Pseudomonas maltophilia, Pseudomonas sp., Vibrio
      parahaemolyticus, Bacillus cereus, Bacillus smithii 1 and Bacillus smithii 2. The
      isolates were capable of tolerating more than 1000 mg/l of arsenate and 749 mg/l
      of arsenite. Likewise, bioaccumulation capability was highest with M. roseus
      (85.61%) and the least with B. smithii (47.88%) indicating the potential of the
      organisms in arsenic resistance and most probably in bioremediation.

PMID- 21868147
TI  - A stage-for-stage and grade-for-grade analysis of cancer-specific mortality rates
      in renal cell carcinoma according to age: a competing-risks regression analysis.
AB  - BACKGROUND: The association of advanced age and cancer control outcomes shows
      discordant findings. OBJECTIVE: To evaluate the effect of age on cancer control
      outcomes in a large population-based cohort of patients diagnosed with renal cell
      carcinoma (RCC) of all stages. DESIGN, SETTING, AND PARTICIPANTS: Using the
      Surveillance Epidemiology and End Results database, 36 333 patients with RCC were
      identified. The population was stratified according to age:<50, 50-59, 60-69, 70
      79, and >=80 yr. The effect of age on cancer control outcomes was evaluated using
      competing-risks regression models. Analyses were repeated stage for stage and
      grade for grade. MEASUREMENTS: Cancer-specific mortality (CSM) was measured.
      RESULTS AND LIMITATIONS: Age categories 50-59, 60-69, 70-79, and >=80 yr
      respectively portended a 1.4-, 1.5-, 1.6-, and 1.9-fold higher risk of CSM than
      age category <50 yr (all p < 0.001). The effect of advanced age was particularly
      detrimental in patients with stage I disease: 1.8-, 2.3-, 3.2-, and 3.8-fold
      higher CSM risk for the same age groups, respectively (all p<0.001). The effect
      of age on CSM was at its peak in patients with stage I, low-grade RCC (1.6-, 2.2
      , 3.6-, and 4.3-fold, respectively; all p<0.001) and remained elevated in stage
      I, high-grade RCC (2.2-, 2.6-, 2.4-, and 3.0-fold higher, respectively; all
      p<0.05). Conversely, its effect was virtually absent in patients with stage II-IV
      RCC. CONCLUSIONS: Our data suggest that stage I RCC may behave in a more
      aggressive fashion in elderly patients. Further studies are required to confirm
      the current findings.

PMID- 21868148
TI  - Competing-risks analysis for renal cell carcinoma: how do we accurately
      communicate the risks and benefits of treatment to patients?

PMID- 21868149
TI  - Vasogenic erectile dysfunction Topiramate-induced.
AB  - Reversible erectile dysfunction due to Topiramate has been linked to the effect
      of this antiepileptic drug on reproductive hormones levels. We described two
      epileptic male patients which experienced erectile dysfunction during Topiramate
      treatment. Serum sexual hormones were tested during treatment and at several time
      intervals following drug discontinuation. Topiramate did not seem to affect
      plasma levels of total, free and bioavailable testosterone and sex hormone
      binding globulin. Since Topiramate erectile dysfunctions could not be related to
      changes in reproductive hormones levels, a vasogenic mechanism must be
      considered.

PMID- 21868150
TI  - Genetically engineered human neural stem cells with rabbit carboxyl esterase can
      target brain metastasis from breast cancer.
AB  - Neural stem cells (NSCs) led to the development of a novel strategy for
      delivering therapeutic genes to tumors. NSCs expressing rabbit carboxyl esterase
      (F3.CE), which activates CPT-11, significantly inhibited the growth of MDA-MB-435
      cells in the presence of CPT-11. F3.CE cells migrated selectively into the brain
      metastases located in the opposite hemisphere. The treatment also significantly
      decreased tumor volume in immune-deficient mice bearing MDA-MB-435 tumors when
      F3.CE cells were transplanted into the contralateral hemisphere. The survival
      rate was significantly prolonged with the treatment with F3.CE and CPT-11. This
      strategy may be considered as an effective treatment regimen for brain
      metastases.

PMID- 21868151
TI  - Overexpression of human papillomavirus (HPV) type 16 oncoproteins promotes
      angiogenesis via enhancing HIF-1alpha and VEGF expression in non-small cell lung
      cancer cells.
AB  - HPV-16 infection may play an important role in the development of non-small cell
      lung cancer (NSCLC) among never-smokers. Due to the critical role of angiogenesis
      in NSCLC development, we describe here the effect of HPV-16 oncoproteins on
      angiogenesis in NSCLC and the underlying mechanisms. We found that overexpression
      of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted
      angiogenesis both in vitro and in vivo, and correspondingly, an enhanced
      expression of HIF-1alpha and VEGF, important pro-angiogenic factors in tumor
      angiogenesis. Meanwhile, overexpression of HPV-16 oncoproteins also led to HIF
      1alpha-dependent increases in the secretion of several other pro-angiogenic
      factors, including IL-8. Our findings suggest that HPV-16 oncoproteins contribute
      to the development of NSCLC possibly by promoting HIF-1alpha/VEGF-mediated tumor
      angiogenesis.

PMID- 21868153
TI  - Synthesis of TiO2 nano-powders prepared from purified sulphate leach liquor of
      red mud.
AB  - The research work presented in this paper is focused on the development of a
      purification process of red mud sulphate leach liquor for the recovery of
      titanium oxide (TiO(2)) nano-powders in the form of anatase. Initially, titanium
      was extracted over iron and aluminium from the leach liquor by solvent extraction
      using Cyanex 272 in toluene, at pH: 0.3 and T: 25 degrees C, with 40% extractant
      concentration. Stripping of the loaded, with titanium, organic phase was carried
      out by diluted HCl (3 mol/L) at ambient temperature. Finally, the recovery of
      titanium nano-powder, in the form of anatase, was performed by chemical
      precipitation at pH: 6 and T: 95 degrees C, using 10 wt% MgO pulp as neutralizing
      agent. The produced precipitates were characterized by X-ray diffraction analysis
      (XRD), Fourier transform infrared spectroscopy (FT-IR) and
      thermogravimetric/differential thermal analysis (TGA/DTA). Their morphological
      characteristics and microstructure were studied by scanning electron microscopy
      (SEM). High grade titanium white precipitate, in the form of anatase, was
      obtained. Iron concentration in the precipitate did not exceed 0.3%, whereas no
      aluminium was detected.

PMID- 21868152
TI  - Phenol determination on HDTMA-bentonite-based electrodes.
AB  - The partial and complete substitution of cations in the interlayer region of clay
      with different amounts of hexadecyl trimethylammonium bromide (HDTMABr) was
      performed. The aim was to synthesize organo-bentonites to be used as constituents
      of porous electrodes for the electrooxidation of phenol. Domestic clay from
      Bogovina was subjected to a common procedure of the production of organo
      bentonites. It included the following steps: grinding, sieving, Na-exchange,
      cation exchange and drying. The samples were characterized by X-ray diffraction
      (XRD) analysis, while the textural properties were evaluated by nitrogen
      physisorption. The multisweep cyclic voltammetry was applied to analyze the
      behavior of the clay modified glassy carbon electrode. The influences of the
      surfactant loading and pH of the support electrolyte were investigated. Rapid
      deactivation of electrodes occurred in an acidic environment, while good
      stability of the investigated electrodes was obtained in alkaline medium.

PMID- 21868154
TI  - Mutagenicity of quaternary ammonium salts containing carbohydrate moieties.
AB  - Quaternary ammonium salts are widely used in industrial, agricultural, healthcare
      and domestic applications. They are believed to be safe compounds, with little or
      no health hazard to humans. However, in this report, we demonstrate that a series
      of newly synthesized quaternary ammonium salts containing carbohydrate moieties
      reveal potent mutagenic activities, as assessed by using the Vibrio harveyi
      bioluminescence mutagenicity test. D-Gluco- and D-galacto-derivatives were found
      to have a higher mutagenic potential than D-manno-derivatives. Among the former
      groups of compounds, the N-[2-(D-glycopyranosyloxy)ethyl]-N,N,N-trimethylaminium
      salts were of the highest activity in the mutagenicity assay. These results
      suggest that the safety of quaternary ammonium salts may be lower than previously
      supposed, indicating a need for testing such compounds for their mutagenicity.

PMID- 21868156
TI  - Production of laccase and decolouration of the textile dye Remazol Brilliant Blue
      R in temporary immersion bioreactors.
AB  - Laccase production by Trametes pubescens grown on sunflower-seed shells (SS)
      under solid-state fermentation (SFF) conditions in temporary immersion
      bioreactors was studied. Three immersion cycles were considered: 1 min immersed
      and 9 min non-immersed, 1 min immersed and 30 min non-immersed and 1 min immersed
      and 60 min non-immersed. The latter led to the highest laccase activities (4000
      6000 Ul(-1)). Also, the in vitro and in vivo decolouration of the recalcitrant
      textile dye Remazol Brilliant Blue R (RBBR) was assessed. It was found that RBBR
      (133.33 mg l(-1)) was efficiently decolourised by T. pubencens grown on SS under
      SSF conditions in temporary immersion bioreactors in five successive batches. The
      percentage of RBBR decolouration was higher than 55% in 4h and around 70% in 24h
      in all the batches. However, it was found that RBBR decolouration by the crude
      culture filtrates was more advantageous. Thus, an RBBR decolouration percentage
      of nearly 80% in 2h was obtained.

PMID- 21868155
TI  - Alkaline hydrothermal synthesis of homogeneous titania microspheres with urchin
      like nanoarchitectures for dye effluent treatments.
AB  - The heterogeneous photocatalysis technique to treat dye effluents demands
      micrometer-sized titania aggregates with one-dimensional nanostructures, which
      possess high photocatalytic activity and at the same time facilitate the catalyst
      recovery from a slurry system. In this study, the solution remained after
      interactions between metallic Ti and hydrogen peroxide was subjected to an
      alkaline hydrothermal treatment. Microspheres with extremely uniform sizes of ca.
      2 MUm in diameter were achieved after a subsequent proton exchange followed by
      calcination in air. The microspheres were urchin-like aggregates of radially
      assembled nanowires, which consisted of chain-like anatase single crystallites
      with an average diameter of 20-25 nm. The homogeneous microspheres calcinated at
      600 degrees C possessed a surface area of 45.4m(2)/g and exhibited an excellent
      activity to assist photodegradation of rhodamine B in water, which is
      significantly higher than that of P25 titania nanoparticles. Because of the much
      easier recovery of the photocatalyst, the homogeneous microspheres synthesized
      herein may find practical applications in efficient photocatalytic treatments of
      dye effluents.

PMID- 21868157
TI  - Photodegradation of propranolol by Fe(III)-citrate complexes: kinetics, mechanism
      and effect of environmental media.
AB  - Photogeneration of HO was optimized in Fe(III)-citrate solution within the pH
      range of 3.0-9.0 to investigate its photoreactivity at neutral pH without the
      addition of H(2)O(2) under simulated sunlight. The generation of HO decreased
      with increasing pH within the range of 6.0-9.0 at the Fe(III)-to-citrate ratio of
      10:50 (10(-6)M). However, when the concentration of citrate increased to 1.5 *
      10(-4)M, the formation rate of HO increased in the order of pH
      9.0<3.0<7.0<4.0<5.0. The pH-dependent HO production was governed by the stability
      of Fe(II)/Fe(II)-citrate and the amount of O(2)(-) in the solution. Propranolol
      can be efficiently photodegraded in Fe(III)-citrate system at pH 7.0 with pseudo
      first-order constant 3.1 * 10(-4)s(-1). HO was verified to be the main reactive
      oxygen species (ROS) responsible for the photodegradation of propranolol. The
      presence of metal ions inhibited the Fe(III)-cit-induced photodegradation in the
      order of Mn(2+)>Cu(2+)>Ca(2+)>Mg(2+). Both humic acid (HA) and fulvic acid (FA)
      markedly suppressed the degradation of propranolol. Moreover, the iron in Fe(III)
      citrate system was reused by a simple addition of citrate to the reaction
      solution. By GC-MS analysis, the photoproducts of the propranolol were identified
      and the degradation pathway was proposed. This work suggests that Fe(III)-citrate
      complexes are good alternative for the advanced treatment of organic pollutants
      at neutral pH in aqueous solution.

PMID- 21868158
TI  - Efficient capture of SO2 by a binary mixture of caprolactam tetrabutyl ammonium
      bromide ionic liquid and water.
AB  - The solubility of SO(2) in a binary mixture of water and caprolactam tetrabutyl
      ammonium bromide ionic liquid (CPL-TBAB IL) was investigated. Though the ionic
      liquid and water were fully miscible, a phase separation occurred when SO(2) was
      introduced into the mixture. The SO(2) concentrated in the lower layer, and it
      could be released by heating the solution under reduced pressure (382.2K, 10.1
      kPa). After desorption, the mixture could be reused to absorb SO(2). It was found
      that SO(2) acts as a switch to cause the water and CPL-TBAB IL to phase separate,
      and the mechanics of this phase separation process was studied by gas
      chromatography-mass spectrometry, fourier transform-infrared spectroscopy and
      Karl-Fisher titration. The absorption and desorption of SO(2) in the CPL
      TBAB/water mixtures were reversible.

PMID- 21868159
TI  - Analysis of supercritical water oxidation for detoxification of waste organic
      solvent in university based on life cycle assessment.
AB  - Spray incineration and supercritical water oxidation (SCWO) processes have been
      used for detoxifying waste organic fluids in the University of Tokyo. In this
      study, we aim to elucidate the environmental aspects of these waste treatment
      processes by life cycle assessment (LCA). Through the investigation of actual
      plants, the inventory data and other characteristics of actual plants were
      collected and analyzed. To confirm the potential of SCWO, three modification
      types of the process and operation were considered and assessed on the basis of
      estimated inventory data. The results demonstrate that spray incineration has
      less environmental impact than SCWO in all scenarios. However, SCWO has various
      advantages for installation as a treatment process in universities such as
      negligible risk of creating dioxins and particulate matter. Proper choice of the
      treatment method for organic waste fluid requires a comprehensive analysis of
      risks. Spray incineration poses the risk of providing dioxins and particulate
      matter, while SCWO has such risk at negligible level. This means that waste
      including concerned materials related to such emission should be treated by SCWO.
      Using the right technologies for the right tasks in the detoxification of
      hazardous materials should be implemented for sustainable universities.

PMID- 21868160
TI  - Influence of the adjuvants in a commercial formulation of the fungicide "Switch"
      on the adsorption of their active ingredients: cyprodinil and fludioxonil, on
      soils devoted to vineyard.
AB  - The objective of this work was to assess the effect of adjuvants in the sorption
      in soils of the fungicides, cyprodinil and fludioxonil, usually applied together
      in a mixture commonly called 'Switch'. Water suspensions of a commercial
      formulation of Switch were used in phase partition experiments for a set of
      selected soils from vineyards. A clean-up procedure of the supernatant was
      developed for the phase separation in presence of the adjuvants prior to
      quantification of cyprodinil and fludioxonil. The maximum sorption on the solid
      phase (which includes soil and other solids from the commercial formulation of
      Switch) was 2000 mg kg(-1) for fludioxonil and 3000 mg kg(-1) for cyprodinil
      after incubation with 800 mg L(-1) of Switch. However, adsorption to soil
      particles were lower; fludioxonil concentrations adsorbed in soils range from 50
      to 80 mg kg(-1) of soil and cyprodinil concentrations range from 120 to 260 mg
      kg(-1) of soil. Adjuvants increased the solubility of fludioxonil in pure water
      at 25  degrees C up to 5 times that of the pure substance (from 1.8 to 9 mg L(-1)
      in control samples), and show a strong influence on the adsorption in soil. Soil
      pH, effective cation exchange capacity and copper content due to past anti fungal
      copper-based sprays, have also influence on the adsorption of the active
      ingredients in presence of adjuvants.

PMID- 21868161
TI  - Size-dependent enrichment of waste slag aggregate fragments abraded from asphalt
      concrete.
AB  - Authors consider the environmental prospects of using melted waste slag as the
      aggregate for asphalt pavement. In particular, the enrichment of slag-derived
      fragments in fine abrasion dust particles originated from slag asphalt concrete
      and its size dependency were concerned. A series of surface abrasion tests for
      asphalt concrete specimens, containing only natural aggregates as reference or 30
      wt% of substituted slag aggregates, were performed. Although two of three slag
      asphalt concretes generated 1.5-3.0 times larger amount of abrasion dust than the
      reference asphalt concrete did, it could not be explained only by abrasion
      resistance of slag. The enrichment of slag-derived fragments in abrasion dust,
      estimated on the basis of the peak intensity of quartz and heavy metal
      concentrations, had size dependency for all slag-asphalt concretes. Slag-derived
      fragments were enriched in abrasion dust particles with diameters of 150-1000
      MUm. Enrichment factors were 1.4-2.1. In contrast, there was no enrichment in
      abrasion dust particles with diameter less than 75 MUm. This suggests that prior
      airborne-size fragmentation of substituted slag aggregates does not need to be
      considered for tested slag aggregates when environmental risks of abrasion dust
      of slag-asphalt pavement are assessed.

PMID- 21868162
TI  - Effects of lead on neurogenesis during zebrafish embryonic brain development.
AB  - Lead neurotoxicity has caused wide public concern in recent decades, yet little
      is known about its effects on cellular and molecular mechanisms during the
      sensitive early life stages of animals. This study examines neurological deficits
      caused by lead acetate (Pb) during early embryonic stages in the zebrafish (Danio
      rerio) and further explores its potential molecular mechanism. Zebrafish embryos
      showed varying levels of toxicity, which was proportional to the concentration of
      Pb to which the embryos were exposed. Following Pb exposure (0.2mM), embryos
      showed obvious neurotoxic symptoms with "sluggish" action, slow swimming
      movements and slow escape action. Whole mount in situ hybridization showed that
      gfap and huC gene expression patterns decreased significantly throughout the
      brains of the Pb-treated embryos, particularly in the diencephalon region. RT-PCR
      further proved the downregulation of the two genes. However, ngn1 and crestin
      gene expression patterns were similar in both the Pb-treated embryos and the
      control embryos. The TUNEL assay demonstrated that the reduction of nerve cells
      was due to increased apoptosis of neuron and glia cells. In conclusion, these
      findings identify that Pb-induced neurotoxicity can be caused by impaired
      neurogenesis, resulting in markedly increased apoptosis of special types of
      neural cells, neuron and glia cells.

PMID- 21868163
TI  - Radiation damage evaluation on concrete within a facility for Selective
      Production of Exotic Species (SPES Project), Italy.
AB  - Concrete is commonly used as a biological shield against nuclear radiation. As
      long as, in the design of nuclear facilities, its load carrying capacity is
      required together with its shielding properties, changes in the mechanical
      properties due to nuclear radiation are of particular significance and may have
      to be taken into account in such circumstances. The study presented here allows
      for reaching first evidences on the behavior of concrete when exposed to nuclear
      radiation in order to evaluate the consequent effect on the mechanical field, by
      means of a proper definition of the radiation damage, strictly connected with the
      strength properties of the building material. Experimental evidences on the decay
      of the mechanical modulus of concrete have allowed for implementing the required
      damage law within a 3D F.E. research code which accounts for the coupling among
      moisture, heat transfer and the mechanical field in concrete treated as a fully
      coupled porous medium. The development of the damage front in a concrete
      shielding wall is analyzed under neutron radiation and results within the wall
      thickness are reported for long-term radiation spans and several concrete
      mixtures in order to discuss the resulting shielding properties.

PMID- 21868164
TI  - Lignin and tannin toxicity to Phaeodactylum tricornutum (Bohlin).
AB  - Lignin and tannin are widespread natural compounds traditionally used in tannery
      industries. Their presence is commonly detected in textile wastewater showing
      potential toxicity effects within various endpoints onto sea water organisms that
      generally represent the ultimate target of discharged effluents. Most data are
      available only as nominal concentrations or percentage volume of wastewater
      having an unknown lignin and tannin content. The aim of this study was to provide
      the ecotoxicological characterisation of both compounds considering as testing
      species the marine alga Phaeodactylum tricornutum (Bohlin). Lignin and tannin
      showed an E(r)C(50) of 113.84(100.90-128.45)mg/L and 26.04(20.10-33.95)mg/L,
      respectively. NOEC and LOEC values were together <0.1mg/L and 0.1mg/L, in that
      order. Moreover, it was observed a morphological change of the algae fusiform
      shape occurring only at tannin concentrations >= 75 mg/L and <185 mg/L.

PMID- 21868165
TI  - Trigeminocervical complex responses after lesioning dopaminergic A11 nucleus are
      modified by dopamine and serotonin mechanisms.
AB  - Both serotonergic and dopaminergic receptor modulation can alter trigeminal
      nociceptive processing, and descending A11 dopaminergic projections can affect
      trigeminal nociceptive transmission. Here we aimed to test the interaction
      between dopamine D(2) and serotonin 5-HT(1B/1D) receptors and their individual
      and combined effects in order to better understand the relationship of the
      descending influences of these systems on nociceptive trigeminovascular
      afferents. Extracellular recordings were made in the rat trigeminocervical
      complex in response to electrical stimulation of the dura mater and mechanical
      noxious and innocuous stimulation of the ipsilateral ophthalmic dermatome. The
      A11 nucleus was lesioned, and following the resultant facilitation of neuronal
      firing, one of a selective 5-HT(1B/1D) receptor agonist (naratriptan), selective
      5-HT(1B/1D) receptor antagonist (GR127935), a selective D(2)-like receptor
      agonist (quinpirole), and a selective D(1)-like receptor agonist (dihydrexidine),
      or a combination of the above, were administered. Both quinpirole and quinpirole
      with naratriptan inhibited firing in the trigeminocervical complex evoked by
      noxious stimuli, reducing it below prelesion baseline, while the response to
      innocuous stimuli was reduced back to baseline. Both naratriptan alone, and
      quinpirole combined with GR127935, inhibited firing in the trigeminocervical
      complex evoked by noxious stimuli, returning it to prelesion baseline, while the
      response to innocuous stimuli remained facilitated. Immunohistochemical staining
      demonstrated D(2)-receptor and 5-HT(1B/1D)-receptor colocalization in the
      trigeminocervical complex. The data suggest that the serotonergic and
      dopaminergic antinociceptive pathways act simultaneously on neurons in the
      trigeminocervical complex, and both amine systems need to be functioning for
      trigeminal sensitization to be reversed.

PMID- 21868166
TI  - Clinical perspectives on preclinical models of bone pain: questions and promises.

PMID- 21868167
TI  - Occurrence of Giardia and Cryptosporidium in pigs on Prince Edward Island,
      Canada.
AB  - In a cross-sectional study of 633 pigs from 21 herds on Prince Edward Island,
      Canada (PEI), the prevalence of infection with Cryptosporidium and Giardia, and
      the genotypes and species of isolates were determined in order to establish the
      zoonotic potential of pigs in this region. As determined by direct
      immunofluorescence microscopy (DFA), 18 herds (86%) and 163 animals (26%; 95% CI:
      22-29%) tested positive for Cryptosporidium, while just 3 herds (14%) and 6
      animals (1%; 95% CI: 0.4-2%) tested positive for Giardia. Cryptosporidium spp.
      isolates were detected in 39% (95% CI: 34-44%) of weanlings (1-3 months of age)
      and 9% (95% CI: 6-13) of sows (>8months of age). Molecular characterization using
      the 18S rDNA and HSP70 gene fragments revealed the presence of Cryptosporidium
      sp. pig genotype II, C. suis, C. parvum, and Cryptosporidium sp. mouse genotype.
      Among the 113 isolates of Cryptosporidium spp. successfully genotyped, pig
      genotype II (61%) predominated, with C. suis (36%) being the next most prominant
      isolate. C. parvum (2%; two isolates) and Cryptosporidium sp. mouse genotype
      (0.9%; one isolate) were only occasionally isolated. The only two Cryptosporidium
      positive genotyped isolates from sows included one each of C. suis and
      Cryptosporidium sp. pig genotype II. All but one of the six Giardia positive
      isolates were detected in weanling pigs. None of the Giardia-positive isolates
      was amenable to PCR. This study demonstrates that Cryptosporidium spp. are highly
      prevalent in pigs on PEI, Canada, are found mostly in weanlings (1-3 months of
      age). Furthermore, the pigs are primarily infected by the host-specific genotypes
      and species, Cryptosporidium sp. pig genotype II and C. suis, whereas the
      zoonotic C. parvum is rare. Giardia duodenalis is only occasionally found in
      pigs. These findings suggest that domestic pigs on PEI, Canada, likely do not
      pose a significant health risk to humans from these parasites.

PMID- 21868168
TI  - Differential prevalence of alcohol use among 2-year and 4-year college students.
AB  - PURPOSE: To determine whether alcohol use behaviors and alcohol-related
      consequences differed among students attending two-year versus four-year
      colleges. METHODS: Participants (N=13,700) from 7 two-year and 11 four-year
      colleges completed the 2010 College Student Health Survey. Alcohol use behaviors
      included past year alcohol use, past month alcohol use, and binge drinking over
      the past two weeks. Alcohol-related factors included average calculated blood
      alcohol level and average number of alcohol-related consequences. Cross-sectional
      mixed-effects regression analyses were conducted to determine if the prevalence
      of alcohol-related behaviors and consequences differed among two-year and four
      year students. RESULTS: Students attending four-year colleges, particularly
      males, were more likely to report past year alcohol use, past month alcohol use,
      and binge drinking, as well as a higher average blood alcohol content and a
      greater number of alcohol-related consequences than their two-year counterparts
      (p<0.05). Among female students there were fewer differences between two-year and
      four-year college students. Many differences remained after adjusting for socio
      demographic factors (e.g., age, race/ethnicity), however, with the addition of
      living situation as a covariate, several of the differences among males were no
      longer significant. CONCLUSIONS: Significant differences in alcohol-related
      behaviors and consequences exist among students attending two-year versus four
      year colleges. While the prevalence of alcohol-related behaviors and consequences
      was lower among two-year college students, they are not a population to be over
      looked. The prevalence of alcohol use remains high among both two-year and four
      year college students, making it important for researchers to design appropriate
      interventions for all students regardless of the type of institution being
      attended.

PMID- 21868169
TI  - Mediators of the relationship between religiousness/spirituality and alcohol
      problems in an adult community sample.
AB  - Johnson et al. (2008b) reported that, in a college student sample, the effect of
      religiousness on alcohol use was mediated by negative beliefs about alcohol,
      social influences, and spiritual well-being, and that these variables in turn
      impacted alcohol use and problems both directly and indirectly via motives for
      drinking. This study attempted to replicate those findings in a sample of
      community dwelling adults (N=211). The effect of Religious/Spiritual Involvement
      was mediated by Negative Beliefs about Alcohol, Social Modeling, and Spiritual
      Well-Being. However, Social Modeling had stronger relationships with motives for
      drinking and alcohol consumption than the other two mediators. The effect of
      Religious Struggle on Alcohol Problems was mediated by Spiritual Well-Being and
      coping motives for drinking. Results provide further support for the motivational
      model of alcohol use and suggest plausible mechanisms by which religiousness
      could causally impact alcohol use and problems. Religious struggle may be a
      clinically significant correlate of alcohol problems.

PMID- 21868170
TI  - Correlates of non-medical prescription drug use among a cohort of injection drug
      users in Baltimore City.
AB  - Despite reports of increasing non-medical prescription drug use, relatively few
      studies have systematically evaluated the prevalence and correlates of non
      medical prescription drug use, particularly in populations that might be
      especially vulnerable (e.g., injection drug users [IDUs]). We examined factors
      associated with non-medical prescription drug use among a community-based cohort
      of current and former IDUs in Baltimore (The ALIVE Study). We conducted a cross
      sectional analysis of data from cohort participants that responded to a survey
      that included questions on non-medical prescription drug use between 2005-06
      (n=1320). Non-medical prescription drug use was considered to be use of any of
      the following: Opiates (Oxycontin, Percocet), Benzodiazepines or Clonidine,
      purchased on the street and taken orally within the last six months. Data on
      other covariates of interest (e.g., demographics, substance use, general health)
      was obtained through a standardized interview. The median age was 46 years; 66%
      were male, 85% were African-American. Twenty one percent reported any non-medical
      prescription drug use; 12% reported using more than one drug. Non-medical use of
      opiates was most common (17%). In multivariate analysis, non-medical prescription
      drug use was significantly associated with Caucasian race (prevalence ratio [PR]:
      1.79), self-reported bodily pain (PR: 1.58), hazardous alcohol use (PR: 1.47),
      marijuana use (PR: 1.65), non-injection cocaine/heroin use (PR: 1.70), diverted
      use of buprenorphine (PR: 1.51) or methadone (PR: 2.51), and active injection
      drug use (PR: 3.50; p<0.05 for all). The association between bodily pain and non
      medical prescription drug use was stronger among persons that were not using
      substances (marijuana, injecting drugs, snorting/smoking heroin, cocaine, using
      crack) as compared to those using these substances. The high prevalence of non
      medical prescription drug use among this population warrants further research and
      action. Information on the risks of nonmedical prescription drug use especially
      overdose, should be incorporated into interventions targeted at IDUs.

PMID- 21868171
TI  - Associations between binge and heavy drinking and health behaviors in a
      nationally representative sample.
AB  - BACKGROUND: Binge and heavy drinking are noted in the literature for their
      relatively high prevalence and adverse health-related effects. DESIGN AND
      PARTICIPANTS: We used data from the 2006 Behavioral Risk Factor Surveillance
      Survey (BRFSS) to determine the associations between binge and heavy drinking and
      a wide range of health-related variables, including positive and negative health
      behaviors, preventive care practices, and quality of life indices in a nationally
      representative sample of 344,793 adults. RESULTS: Rates of binge and heavy
      drinking in the current sample were 15% and 5%, respectively. Binge and heavy
      drinking were more common among men, younger adults, and individuals with higher
      incomes and at least some college education. After controlling for relevant
      demographic variables, binge and heavy drinking were associated with a number of
      adverse health-related and preventive care behaviors (e.g., smoking, failing to
      receive a mammogram), as well as less life satisfaction and a greater number of
      poor mental health days than those who did not engage in these drinking
      behaviors. Interestingly, binge and heavy drinking were also associated with some
      positive health-related variables (e.g., recent physical activity, positive
      perceptions of one's own health). CONCLUSIONS: The current study findings provide
      additional information regarding the relations between health-related attitudes
      and behaviors and binge and heavy drinking in the U.S. population. Implications
      of study findings are discussed.

PMID- 21868172
TI  - Smoking susceptibility among students followed from grade six to eight.
AB  - BACKGROUND: Smoking is a leading risk factor for heart disease and cancer. By
      identifying factors associated with smoking onset, more effective prevention
      programs can be developed. Research questions are (1) does smoking susceptibility
      status change from grade six to eight, (2) are indicators of risk (perceived
      harm, smoking susceptibility status, positive peers, and resilience) measured in
      sixth grade associated with smoking susceptibility status in eighth grade and,
      (3) are there differences by gender in either research question? METHODS: The
      current study is a secondary analysis of data collected during the evaluation of
      a Safe Schools Healthy Students Project. Students were followed from grade six to
      grade eight, with survey data collected in each grade from August 2006 to
      December 2008. Participants (n=577) were in grade six at baseline, 52% were girls
      and 57% identified as White, non-Hispanic. RESULTS: From grade six to grade eight
      the number of students in the high smoking susceptibility status doubled (5% to
      17%). More boys than girls moved into the high susceptibility group over time. By
      eighth grade, boys were twice as likely to belong to the high smoking
      susceptibility group compared to girls (p=0.01). Multiple logistic regression
      models showed that the positive peers' variable in grade six was protective for
      girls in their reported smoking susceptibility in grade eight. In contrast,
      higher resilience scores in grade six were protective for boys' reported smoking
      susceptibility in grade eight. CONCLUSIONS: Smoking susceptibility rose over time
      for all adolescents, but boys had notably sharper increases. Positive peers and
      having resources important to resilience may be beneficial in preventing the
      attitudes that support smoking initiation. Based on these results, we recommend
      gender-tailored, school-based smoking prevention programs that begin in grade
      six.

PMID- 21868173
TI  - Dose-volume parameters predict for the development of chest wall pain after
      stereotactic body radiation for lung cancer.
AB  - PURPOSE: Chest wall (CW) pain has recently been recognized as an important
      adverse effect of stereotactic body radiation therapy (SBRT) for non-small-cell
      lung cancer (NSCLC). We developed a dose-volume model to predict the development
      of this toxicity. METHODS AND MATERIALS: A total of 126 patients with primary,
      clinically node-negative NSCLC received three to five fractions of SBRT to doses
      of 40-60 Gy and were prospectively followed. The dose-absolute volume histograms
      of two different definitions of the CW as an organ at risk (CW3cm and CW2cm) were
      examined for all 126 patients. RESULTS: With a median follow-up of 16 months, the
      2-year estimated actuarial incidence of Grade >= 2 CW pain was 39%. The median
      time to onset of Grade >= 2 CW pain (National Cancer Institute Common Terminology
      Criteria for Adverse Events, Version 3.0) was 9 months. There was no predictive
      advantage for biologically corrected dose over physical dose. Neither fraction
      number (p = 0.07) nor prescription dose (p = 0.07) were significantly correlated
      with the development of Grade >= 2 CW pain. Cox Proportional Hazards analysis
      identified significant correlation with a broad range of dose-volume
      combinations, with the CW volume receiving 30 Gy (V30) as one of the strongest
      predictors (p < 0.001). CW2cm consistently enabled better prediction of CW
      toxicity. When a physical dose of 30 Gy was received by more than 70 cm(3) of
      CW2cm, there was a significant correlation with Grade >= 2 CW pain (p = 0.004).
      CONCLUSIONS: CW toxicity after SBRT is common and long-term follow-up is needed
      to identify affected patients. A volume of CW >= 70 cm(3) receiving 30 Gy is
      significantly correlated with Grade >= 2 CW pain. We are currently applying this
      constraint at our institution for patients receiving thoracic SBRT. An actuarial
      atlas of our data is provided as an electronic supplement to facilitate data
      sharing and meta-analysis relating to CW pain.

PMID- 21868174
TI  - Treatment of locally advanced vaginal cancer with radiochemotherapy and magnetic
      resonance image-guided adaptive brachytherapy: dose-volume parameters and first
      clinical results.
AB  - PURPOSE: To investigate the clinical feasibility of magnetic resonance image
      guided adaptive brachytherapy (IGABT) for patients with locally advanced vaginal
      cancer and to report treatment outcomes. METHODS AND MATERIALS: Thirteen patients
      with vaginal cancer were treated with external beam radiotherapy (45-50.4 Gy)
      plus IGABT with or without chemotherapy. Distribution of International Federation
      of Gynecology and Obstetrics stages among patients were as follows: 4 patients
      had Stage II cancer, 5 patients had Stage III cancer, and 4 patients had Stage IV
      cancer. The concept of IGABT as developed for cervix cancer was transferred and
      adapted for vaginal cancer, with corresponding treatment planning and reporting.
      Doses were converted to the equivalent dose in 2 Gy, applying the linear
      quadratic model (alpha/beta = 10 Gy for tumor; alpha/beta = 3 for organs at
      risk). Endpoints studied were gross tumor volume (GTV), dose-volume parameters
      for high-risk clinical target volume (HRCTV), and organs at risk, local control
      (LC), adverse side effects, and survival. RESULTS: The mean GTV (+/- 1 standard
      deviation) at diagnosis was 45.3 (+/-30) cm(3), and the mean GTV at brachytherapy
      was 10 (+/-14) cm(3). The mean D90 for the HRCTV was 86 (+/-13) Gy. The mean D2cc
      for bladder, urethra, rectum, and sigmoid colon were 80 (+/-20) Gy, 76 (+/-16)
      Gy, 70 (+/-9) Gy, and 60 (+/-9) Gy, respectively. After a median follow-up of 43
      months (range, 19-87 months), one local recurrence and two distant metastases
      cases were observed. Actuarial LC and overall survival rates at 3 years were 92%
      and 85%. One patient with Stage IVA and 1 patient with Stage III disease
      experienced fistulas (one vesicovaginal, one rectovaginal), and 1 patient
      developed periurethral necrosis. CONCLUSIONS: The concept of IGABT, originally
      developed for treating cervix cancer, appears to be applicable to vaginal cancer
      treatment with only minor adaptations. Dose-volume parameters for HRCTV and
      organs at risk are in a comparable range. First clinical results indicate
      excellent LC. Further prospective multicenter studies are needed to establish
      this method and to confirm these results.

PMID- 21868175
TI  - Negative reinforcement smoking outcome expectancies are associated with affective
      response to acute nicotine administration and abstinence.
AB  - BACKGROUND: Negative affect is an important predictor of smoking behavior, and
      many smokers believe that smoking reduces negative affect. However, it is unclear
      whether such beliefs, known as negative reinforcement smoking outcome
      expectancies (NRSOE), are associated with changes in negative affect in response
      to nicotine deprivation and administration. METHODS: Smokers (N=114) participated
      in 4 sessions that balanced overnight smoking deprivation (12-h deprived vs. ad
      lib) and nasal spray administration (nicotine vs. placebo). Corrugator supercilii
      (COR) EMG, skin conductance (SCR), and in-session ratings were collected while
      the participants viewed affective, cigarette-related, and neutral slides.
      Retrospective questionnaire data were collected prior to slide viewing. NRSOE
      were determined using the Smoking Consequences Questionnaire - Adult Nicotine
      Affect Reduction scale (SCQ-NAR). RESULTS: High scores on the SCQ-NAR were
      associated with smaller COR EMG to unpleasant slides following nicotine nasal
      spray administration compared to placebo spray, regardless of overnight
      deprivation. Smokers who had high scores on the SCQ-NAR had smaller SCR,
      following nicotine nasal spray administration compared to placebo spray, but only
      after overnight deprivation. The in-session ratings and retrospective
      questionnaire measures indicated that smokers who had high scores on the SCQ-NAR
      experienced greater negative affect and craving, and less positive affect, than
      smokers with low scores on the SCQ-NAR, regardless of nicotine exposure.
      CONCLUSIONS: Our questionnaire results suggest that while smokers who have high
      NRSOE self-report greater overall levels of negative affect and craving, while
      the psychophysiological data suggest that such smokers may experience negative
      affect reduction when blindly administered a dose of nicotine.

PMID- 21868177
TI  - Genetic analysis and antimicrobial susceptibility of Francisella noatunensis
      subsp. orientalis (syn. F. asiatica) isolates from fish.
AB  - Francisella noatunensis subsp. orientalis (syn. F. asiatica) (Fno) is an emergent
      fish pathogen that causes acute to chronic disease in a wide variety of
      freshwater, brackish and marine fish. Due to the emergent nature of this
      bacterium, established protocols to measure antimicrobial susceptibility are
      lacking. In this project we compare three different methods to examine the
      antimicrobial susceptibility (Etest, broth microdilution and disk diffusion) of
      10 different isolates of Fno from two different fish species and four different
      geographic outbreaks from 2006 to 2010. PCR mediated genomic fingerprinting (rep
      PCR) performed on the different isolates confirmed genetic homogeneity amongst
      the different isolates. The in vitro susceptibility data presented here provides
      important baseline data for future research monitoring the development of
      antibiotic resistance among Fno isolates as well as provides invaluable data for
      the development of potential therapeutics.

PMID- 21868176
TI  - The effect of two elementary school-based prevention interventions on being
      offered tobacco and the transition to smoking.
AB  - AIMS: This study sought to more precisely delineate the mechanisms by which two
      early elementary school-based, universal (i.e., applied to the entire population
      regardless of risk status) preventive interventions increased survival to first
      tobacco cigarette smoked. Specifically, we examined whether the interventions'
      effect on survival to first use was via the reduction of offers to smoke and/or
      through preventing the transition from first offer to smoking. METHODS: A total
      of 678 urban first-graders were assigned randomly to the classroom-centered (CC),
      or the family-school partnership (FSP), or a control classroom condition. Youth
      were followed annually until 1 year beyond their anticipated high school
      graduation (mean age ~18 years). Discrete-time survival analyses on 628 youth
      evaluated the impact of the CC and FSP interventions on first tobacco offer and
      initial tobacco smoking once offered. FINDINGS: The risk of being offered tobacco
      was reduced among both CC and FSP intervention groups relative to the control
      group, although the reduction was only statistically significant for the CC
      intervention. Neither intervention condition reduced the transition to smoking
      once offered tobacco to smoke. CONCLUSION: The CC intervention appeared to have
      its effect on survival to first cigarette smoked by delaying the first offer to
      smoke. Preventive interventions focused on refusal skills during the middle
      school years may be necessary to reduce the likelihood of the transition to
      smoking once offered.

PMID- 21868178
TI  - Forensic quest for age determination of bloodstains.
AB  - Bloodstains at crime scenes are among the most important types of evidence for
      forensic investigators. They can be used for DNA-profiling for verifying the
      suspect's identity or for pattern analysis in order to reconstruct the crime.
      However, until now, using bloodstains to determine the time elapsed since the
      crime was committed is still not possible. From a criminalistic point of view, an
      accurate estimation of when the crime was committed enables to verify witnesses'
      statements, limits the number of suspects and assesses alibis. Despite several
      attempts and exploration of many technologies during a century, no method has
      been materialized into forensic practice. This review gives an overview of an
      extensive search in scientific literature of techniques that address the quest
      for age determination of bloodstains. We found that most techniques are
      complementary to each other, in short as well as long term age determination.
      Techniques are compared concerning their sensitivity for short and long term
      ageing of bloodstains and concerning their possible applicability to be used on a
      crime scene. In addition, experimental challenges like substrate variation,
      interdonor variation and environmental influences are addressed. Comparison of
      these techniques contributes to our knowledge of the physics and biochemistry in
      an ageing bloodstain. Further improvement and incorporation of environmental
      factors are necessary to enable age determination of bloodstains to be acceptable
      in court.

PMID- 21868179
TI  - Serious head injury in young children: birth trauma versus non-accidental head
      injury.
AB  - Birth injury of the skull and central nervous system can be a complication of a
      difficult delivery, especially following forceps or vacuum-assisted delivery.
      Birth trauma of the head can also mimic the appearance of a non-accidental head
      injury and is therefore an important differential diagnosis. We report on two
      young infants with serious head injuries. The difficult differential diagnosis
      birth trauma versus non-accidental head injury is discussed and the necessity for
      cooperation between clinicians, forensic doctors and specialized
      neuroradiologists is emphasized.

PMID- 21868180
TI  - Frequency of Alloicoccus otitidis, Streptococcus pneumoniae, Moraxella
      catarrhalis and Haemophilus influenzae in children with otitis media with
      effusion (OME) in Iranian patients.
AB  - OBJECTIVE: To determine the presence of common bacterial agents of otitis media
      with effusion (OME), together with investigation these agent in the adenoid
      tissue and antimicrobial susceptibility pattern of isolated bacteria in Iranian
      children with OME. METHODS: Polymerase chain reaction (PCR) and bacterial culture
      methods were used for detection and isolation of Alloicoccus otitidis,
      Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae in 63
      middle ear fluid samples and 48 adenoid tissues from 48 OME patients. Fifteen
      patients were bilaterally affected. Antimicrobial susceptibility of all bacterial
      isolates were determined by disk agar diffusion (DAD) method. RESULTS: Bacteria
      were isolated from 47% (n=30) of the middle ear fluid samples and 79% (n=38) of
      the adenoid tissue specimens in OME patients. A. otitidis was the most common
      bacterial isolated from the middle ear fluid 23.8% by culture and 36.5% by PCR
      method. S. pneumoniae was the most prevalent pathogen (35.5% and 31.2% by culture
      and PCR) in the adenoid tissues. In 10 patients the same organisms were isolated
      from the middle ear fluid and adenoid tissue. Antimicrobial susceptibility
      pattern showed taht most isolates of bacteria were sensitive to ampicillin,
      Amoxicillin/Clavulanate and fluoroquinolones. CONCLUSION: The present study,
      being the first report on the isolation of A. otitidis by culture method in Iran
      and Asian countries, shows that A. otitidis is the most frequently isolated
      bacterium in Iranian children having otitis media with effusion. In this study A.
      otitidis, S. pneumoniae, H. influenzae and M. catarrhalis are the major bacterial
      pathogens in patients with OME and we found that ampicillin and
      Amoxicillin/Clavulanate have the excellent activity against bacterial agents in
      Iranian children with OME.

PMID- 21868181
TI  - Basaloid squamous cell carcinoma of the larynx--A systematic review.
AB  - OBJECTIVES: This study pools all the cases of Basaloid squamous cell carcinoma of
      the larynx in the English literature to investigate the clinical course of this
      rare clinico-pathological disease entity. METHODS: We found and analyzed 100
      cases with individual patient data from 36 publications spanning 20 years.
      RESULTS: It is a rare disease of the elderly with strong male predominance and
      more common in the supraglottis. Patients typically present with locoregionally
      advanced stage. Surgery alone or combined with radiotherapy is commonly reported.
      It has a worse survival outcome when compared to laryngeal cancers in general.
      Twenty-two percent eventually develop distant metastases with the lung being the
      predominant site. CONCLUSIONS: Given the rarity of this clinical condition and
      the lack of data from studies with adequate number of cases, this systematic
      literature analysis provides the best possible relevant evidence.

PMID- 21868182
TI  - Mapping the double bonds in triglycerides.
AB  - This study presents and validates a theoretical model for estimating the number
      of double bonds in triglyceride molecules using magnetic resonance imaging. The
      model enables reliable estimation of the number of double bonds from a small
      number of time points, as are typically acquired with chemical shift imaging.
      Prior knowledge from the US Department of Agriculture (USDA) is used to constrain
      the properties of triglyceride. Validation in oil phantoms shows agreement
      between the measured number of double bonds and USDA reference values
      (correlation 0.95, significance P=.0003, slope 0.95+/-0.31, intercept 0.08+/
      1.24). Feasibility in a human subject was demonstrated using a long breath-hold
      (43 s) scan.

PMID- 21868183
TI  - Studies of pathology and VEGF expression in rabbit cerebrospinal fluid
      metastasis: application of dynamic contrast-enhanced MRI.
AB  - OBJECTIVE: The objective was to analyze the correlation of dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) with vascular endothelial growth
      factor (VEGF) protein expression and to assess the potential application of DCE
      MRI to the rabbit cerebrospinal fluid (CSF) metastasis model. METHODS: Thirty New
      Zealand rabbits were divided into experimental and control groups. In the
      experimental group, VX2 tumor cells were injected into the subarachnoid space at
      the plane of cisterna magna in 24 rabbits. In the control group, physiological
      saline was injected into the subarachnoid space at the plane of cisterna magna in
      six rabbits. DCE-MRI was performed at multiple time points, and several
      pharmacokinetic parameters, including K(trans), K(ep) and V(e), were calculated.
      Also, VEGF levels in plasma and CSF were evaluated by enzyme-linked immunosorbent
      assay prior to DCE-MRI examination. After DCE-MRI examination, the rabbits were
      sacrificed, and the corresponding tumor specimens were harvested. Hematoxylin
      eosin staining and VEGF immunohistochemical staining were carried out, and VEGF
      expression in the specimens was evaluated by the immunohistochemical scoring
      system. RESULTS: Vascular endothelial growth factor positive staining was
      localized in the cytoplasm and cell membranes of tumor cells, as well as in a
      subset of epithelial cells. Both VEGF immunohistochemical scores and VEGF
      expression in CSF and plasma exhibited positive correlations with K(trans) and
      K(ep) values as demonstrated by rank correlation statistical analysis.
      CONCLUSIONS: Vascular endothelial growth factor expression in plasma and CSF in
      the CSF metastasis model was higher than in normal tissues. Therefore, DCE-MRI
      reliably indicated VEGF expression in the rabbit CSF metastasis model.

PMID- 21868184
TI  - Development of a novel radioimmunoassay to detect autoantibodies to amyloid beta
      peptides in the presence of a cross-reactive therapeutic antibody.
AB  - An increasing need in the development of biotherapeutic agents is the ability to
      monitor a potential autoimmune response to the therapeutic target of interest.
      Unfortunately, the presence of high concentrations of therapeutic antibody can
      hinder such detection, because there is competition for binding in cases where
      epitopes are not structurally distinct. This situation was encountered in the
      development of LY2062430, a therapeutic mid-domain monoclonal anti-amyloid beta
      peptide (Abeta) antibody undergoing clinical trials for the treatment of
      Alzheimer's disease. This communication reports the development and validation of
      a novel radioimmunoassay used to measure potential patient immune responses to
      Abeta in the presence of LY2062430. This assay employs a radioiodinated analog of
      the human amyloid beta 1-40 peptide (Abeta1-40) in which a single amino acid
      substitution of alanine for phenylalanine at position 19 (F19A) effectively
      eliminates binding by LY2062430. In contrast, F19A binding by monoclonal
      antibodies specific for the N- and C-termini of the human Abeta1-40 peptide was
      shown to be unaltered. Additional experiments involving a polyclonal rabbit
      antibody raised against the midregion of Abeta1-40 (residues 15-30) resulted in
      only a slight reduction in binding to the F19A tracer, suggesting that the
      modification does not affect distal epitopes in Abeta1-40 and supporting the
      notion that this conservative substitution produces only subtle change in the
      overall peptide structure. The assay is therefore believed to detect most, if not
      all, patient antibodies to native Abeta peptides. The assay was validated for use
      in clinical trials allowing detection of antibodies to Abeta in human serum in
      the presence of therapeutic concentrations of LY2062430.

PMID- 21868185
TI  - Molecular detection and sequence analysis of hepatitis E virus in patients with
      viral hepatitis from North India.
AB  - Viral hepatitis is a major cause of mortality and morbidity in developing
      countries. Hepatitis E virus (HEV) is responsible for both sporadic and epidemic
      outbreaks of viral hepatitis in India. Here a total of 843 samples were
      collected: 685 from patients with acute viral hepatitis (AVH), 70 from patients
      with fulminant hepatic failure (FHF), 53 from patients with chronic liver disease
      (CLD), 11 from patients with antituberculosis therapy (ATT)-induced jaundice, and
      24 from pregnant women. When tested for anti-HEV IgM, 58.3% of the pregnant
      women, 41.4% of the patients with FHF, 38.6% of the patients with AVH, 9.4% of
      the patients with CLD, and 18.2% of the patients with ATT-induced jaundice tested
      positive. We found that 34% and 16% of the acute hepatitis patients and fulminant
      hepatitis patients, respectively, showed no reactivity to the existing viral
      hepatitis markers and were thus grouped as non A to E. Among the HEV IgM-positive
      cases, males outnumbered females (62.8% versus 37.1%). HEV RNA was found in 35%
      of fulminant and 9.4% of acute hepatitis patients. From phylogenetic analysis, we
      observed that all the isolates were clustered within genotype 1. Critical
      analysis placed the acute isolates along with strains under subtype Ia, while the
      fulminant isolates clustered along with the FHF strain (X98292) under subtype Ic.
      The segregation of HEV isolates from AVH and FHF patients into different subtypes
      raises interesting questions on the molecular basis of HEV disease severity.

PMID- 21868186
TI  - Twelve-month follow-up of aftercare for adolescents with alcohol use disorders.
AB  - Adolescents with alcohol use disorders (AUDs) previously completed a randomized
      controlled outpatient aftercare study (Y. Kaminer, J. A. Burleson, & R. H. Burke,
      2008) in which they were randomly assigned to in-person, brief telephone, or no
      active aftercare. Youth were assessed at end of aftercare and at 3-, 6-, and 12
      month follow-up on frequency and quantity of alcohol use. It was predicted that
      active aftercare (in-person and brief telephone) would be superior to no-active
      aftercare in reducing alcohol use, as shown in the original study. No subject or
      therapy group attributes were significant moderators of outcome. Active aftercare
      in general maintained short-term favorable effects by reducing relapse in youth
      with AUD and should be considered as part of standard procedures in therapeutic
      interventions for all alcohol and other substance use. In-person and the brief
      telephone procedures did not differ in their effectiveness. Structured
      communications with AUD youth during and after treatment by use of electronic
      technology rather than in-person contact might therefore be more fully
      investigated.

PMID- 21868187
TI  - Dramatic dietary fat reduction is feasible for breast cancer patients: Results of
      the randomised study, WINS (UK) - stage 1.
AB  - INTRODUCTION: The influence of dietary fat on breast tumour growth(1) and, more
      recently, on treatment outcomes,(2,3) suggests an important role for dietary
      advice in the future health of breast cancer patients. The Women's Intervention
      Nutrition Study (UK) - Stage 1 assessed the feasibility of achieving and
      maintaining a >= 50% reduction in reported fat intake in postmenopausal, early
      stage breast cancer patients in the UK. METHOD: This study recruited patients in
      South-east England between 2000 and 2005. They were randomly allocated into two
      groups. Group 1 (n = 54), received specific dietary counselling to halve their
      reported fat intake and maintain this low fat intake. Group 2 (n = 53) received
      healthy eating advice only. Dietitian-led group sessions provided support for
      women in both groups over 2 years.(4) Validated four-day diaries were used to
      measure intake. Data analysis used Generalised Linear Model (GLM) for repeated
      measures and logistic regression. RESULTS: A significantly greater proportion of
      women in Group 1 reported a fat intake reduction of >= 50% at 3 months (p < .001)
      and 24 months (p < .001) than in Group 2. The size of the effect of active
      dietary counselling was 37% at 3 months (95%CI: 21-54%) and 35% at 24 months
      (95%CI: 17-53%). Mean fat intake was halved at 3 months and 24 months in Group 1
      only. CONCLUSION: Demonstrating such feasibility is a key step towards defining
      diet's role in the secondary prevention of breast cancer.

PMID- 21868189
TI  - Arthroscopic-assisted repair of avulsed triangular fibrocartilage complex to the
      fovea of the ulnar head: a 2- to 4-year follow-up study.
AB  - PURPOSE: The objective of this study was to conduct a follow-up evaluation of an
      arthroscopic reattachment technique using an avulsed deep component of the
      triangular fibrocartilage complex (dc-TFCC) from the fovea of the distal ulna
      (ulnar fovea). METHODS: A retrospective study was performed on a consecutive
      cohort of 12 patients who underwent arthroscopic reattachment of the avulsed dc
      TFCC into the ulnar fovea over a 24-month period. The mean age was 31 years
      (range, 20 to 50 years). There were 6 men and 6 women. This technique anchors the
      avulsed portion of the dc-TFCC to the ulnar fovea by means of a repair suture
      passed through the created osseous tunnel from the ulnar neck to the foveal
      surface. Postoperative clinical and functional outcomes were quantitatively
      evaluated with the Modified Mayo Wrist Score. The Disabilities of the Arm,
      Shoulder and Hand questionnaire served to assess each patient's subjective
      outcome. A questionnaire regarding each patient's return to his or her previous
      job was also completed. Radiographic evaluation was based on computed tomography
      and magnetic resonance imaging examinations. RESULTS: At the mean follow-up of 30
      months, all patients had significant reduction of wrist pain. The mean Modified
      Mayo Wrist Score was 92.5 +/- 7.5, and all patients were rated as having
      excellent or good clinical results. The Disabilities of the Arm, Shoulder and
      Hand score significantly improved from 59.5 +/- 18.5 to 7.7 +/- 11.9
      postoperatively (P < .0001). Of the 9 working patients, 7 returned to their
      previous work. Two patients had occasional extensor carpi ulnaris tendinitis
      after surgery. Magnetic resonance images at 12 weeks postoperatively showed
      findings indicating attachment of the triangular fibrocartilage complex (TFCC) to
      the fovea. CONCLUSIONS: Arthroscopic reattachment of the avulsed TFCC to the
      ulnar fovea by the described technique is a valid alternative for treating
      avulsion of the foveal TFCC insertion.

PMID- 21868188
TI  - Therapeutic mammaplasties: full local control of breast cancer in one surgical
      stage with frozen section.
AB  - AIM: To evaluate the effectiveness of therapeutic mammoplasty with frozen section
      in achieving negative surgical margins in a single-stage surgery for breast
      cancer. METHODS: Fifty patients affected by early stage breast cancer treated by
      therapeutic mammaplasties were retrospectively reviewed in this study. Fifty-two
      therapeutic mammaplasties were accomplished. After resection the specimen was
      sent to pathologist for examination with frozen section. Tumour positive margins
      were defined as presence of cancerous cells at <= 2 mm from the edge of the
      specimen. In case of positive margins a second large re-excision was accomplished
      intra-operatively. All patients were followed every 4 months for the first 2
      years and twice a year subsequently. RESULTS: Fifty-two procedures were evaluated
      (median follow-up of 72.6 months). The overall survival rate was 98% we had a
      single case of local recurrent disease (1.9%) that progressed to metastatic
      disease and patient's death. Frozen section as a diagnostic tool for
      identification of positive margins has been tested. In conclusion we report a
      sensitivity of 0.83 and a specificity of 0.93; the predictive positive value was
      0.62 and the negative predictive value was 0.97, for a final accuracy of 0.94.
      CONCLUSION: Frozen section coupled to oncoplastic resections allows a proper
      control of local disease and can minimize any second surgical look for margins
      revision.

PMID- 21868190
TI  - A randomized study of the effectiveness of suprascapular nerve block in patient
      satisfaction and outcome after arthroscopic subacromial decompression.
AB  - PURPOSE: The purpose of this study was to evaluate the efficiency of the
      suprascapular nerve (SSN) block in pain reduction after arthroscopic subacromial
      decompression operations and its influence on patient satisfaction. Furthermore,
      we wanted to evaluate whether better perioperative pain management could
      positively influence postoperative shoulder function. METHODS: In this
      prospective, randomized, double-blinded clinical trial, 3 groups of patients-
      each with 15 participants--were treated with SSN block (10 mL of 1% ropivacaine),
      placebo, or a subacromial infiltration of local anesthesia (20 mL of 1%
      ropivacaine). Preoperative and postoperative pain was evaluated with a visual
      analog scale. Functional outcome was measured by the Constant-Murley score, and
      patient satisfaction was measured anecdotally by interview 2 days, 2 weeks, and 6
      weeks after surgery. RESULTS: The SSN group reported significantly lower levels
      of postoperative pain, required significantly less analgesia, had better range of
      motion, and had higher levels of postoperative satisfaction in comparison to the
      subacromial infiltration group and placebo group. CONCLUSIONS: Patients treated
      with SSN blocks had less pain overall, which led to a decreased need for
      analgesics in comparison to the subacromial infiltration and placebo groups.
      Furthermore, patients in the SSN-blocked group achieved better postoperative ROM
      and were significantly more satisfied after surgery.

PMID- 21868191
TI  - [Prevention and treatment of hypotension during spinal anesthesia for elective
      caesarean section: any progress in clinical practice?].

PMID- 21868192
TI  - [Behcet syndrome: thirty comments with lung and vascular injury of peripheral
      vessels].
AB  - INTRODUCTION: Behcet's disease is a systematic vasculitis of unknown cause,
      characterized essentially by eye, cutaneous, articular, neurological and vascular
      manifestations. METHODS: We retrospectively analysed the Behcet's disease cases
      that were followed up in our ward from January 2000 to January 2009. The
      inclusion criteria were those of International Study Group on Behcet's disease
      (aphthosis mouth was required). Data were retrieved and analysed with two
      softwares (Access((r)) and Epi Info((r))). RESULTS: We observed 30 cases with
      vascular lesions on a series of 92 patients with Behcet's disease. Most patients
      were male, with an average age around 40. The venous manifestations, concerning
      essentially the lower limbs (deep and superficial thrombosis) were found at 27
      patients (90 %), and the average of age during the appearance of the venous
      lesions was 40 years. Arterial lesions appear more late in 13 patients (43 %)
      (average of age 43 years). We noted, on the other hand, 11 cases of aneurysms and
      five cases of arterial thrombosis. The use of corticosteroids was necessary in
      all cases in association with the others drugs (anticoagulants, colchicine,
      immunosuppressors). Among the patients having had aneurysms, six were treated
      surgically. The outcome was favorable for most patients. Two patients had
      pulmonary embolism and two post-surgery complications. One patient died in the
      consequences of an intragastric break of an aneurysm of the abdominal aorta.
      CONCLUSION: The vascular involvement in Behcet's disease is manifested primarily
      by thrombophlebitis. Achieving blood pressure, less common, is problematic
      therapeutic because of the recurrent and life threatening.

PMID- 21868193
TI  - Axis or meridian?

PMID- 21868194
TI  - Automated segmentation of micro-CT images of bone formation in calcium phosphate
      scaffolds.
AB  - In this work, we develop and validate an automated micro-computed tomography
      (micro-CT) image segmentation algorithm that accurately and efficiently segments
      bone, calcium phosphate (CaP)-based bone scaffold, and soft tissue. The algorithm
      enables quantitative evaluation of bone growth in CaP scaffolds in our study that
      includes many samples (100+) and large data sets (900 images per sample). The use
      of micro-CT for such applications is otherwise limited because the similarity in
      X-ray attenuation for the two materials makes them indistinguishable. Destructive
      characterization using histological techniques and scanning electron microscopy
      (SEM) has been the standard for CaP scaffolds, but these methods are cumbersome,
      inaccurate, and yield only 2D information. The proposed algorithm exploits
      scaffold periodicity and combines signal analysis, edge detection, and knowledge
      of three-dimensional spatial relationships between bone, CaP scaffold, and soft
      tissue to achieve fast and accurate segmentation. Application of this algorithm
      can lead to a new understanding of the role of CaP and scaffold internal
      structure on patterns and rates of bone growth.

PMID- 21868196
TI  - Dietary patterns and attention deficit hyperactivity disorder among Iranian
      children.
AB  - OBJECTIVE: This study was conducted to assess the relation of major dietary
      patterns identified by factor analysis to attention-deficit/hyperactivity
      disorder (ADHD) in a group of Iranian school-age children. METHODS: This cross
      sectional study was conducted in 375 school-age children in Tehran, Iran. We
      assessed usual dietary intakes by a semiquantitative food-frequency
      questionnaire. The presence of ADHD was diagnosed using the questionnaire of the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Major
      dietary patterns were identified by factor analysis. RESULTS: The prevalence of
      ADHD was 9.7% in this population. We identified four major dietary patterns:
      "healthy," "Western," "sweet," and "fast food." After controlling for potential
      confounders, children in the top quintile of the sweet dietary pattern score had
      greater odds for having ADHD compared with those in the lowest quintile (odds
      ratio 3.95, 95% confidence interval 1.16-15.31, P for trend = 0.03). Greater
      adherence to the fast-food dietary pattern was significantly associated with a
      higher risk of having ADHD (odds ratio 3.21, 95% confidence interval 1.05-10.90,
      P for trend = 0.03). No overall significant associations were seen between the
      healthy or Western dietary pattern and ADHD. CONCLUSION: We found significant
      independent associations between the sweet and fast-food dietary patterns and the
      prevalence of ADHD. Prospective studies are required to confirm these findings.

PMID- 21868197
TI  - Ghrelin and anorexia nervosa: a psychosomatic perspective.
AB  - Anorexia nervosa (AN) is a serious medical illness associated with
      gastrointestinal, metabolic, and psychological complications, and there are no
      effective pharmacologic treatments for the condition. Recent studies have
      suggested that the regulatory peptides, including ghrelin, are involved in the
      pathologic feeding behavior of AN. Previous studies have indicated that plasma
      total ghrelin and acyl ghrelin levels in patients with AN are higher than in
      controls, and the ratio of des-acyl ghrelin to acyl ghrelin in AN tend to be
      higher than in controls. In addition, ghrelin has been reported to stimulate
      appetite and food intake in various diseases, including chronic heart failure,
      chronic obstructive pulmonary disease, and cancer. Because it is speculated that
      difficulties in resolving the underlying psychological condition preclude
      reversal of the pathologic feeding behavior in AN, ghrelin is expected to be
      applied in a clinical setting as a new treatment. In this review, we describe the
      role of ghrelin in the pathophysiology and potential treatment of AN along the
      gut-brain axis.

PMID- 21868195
TI  - HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to
      lupus-associated antigen SmD.
AB  - Although systemic lupus erythematosus (SLE) is a multigenic autoimmune disorder,
      HLA-D is the most dominant genetic susceptibility locus. This study was
      undertaken to investigate the hypothesis that microbial peptides bind HLA-DR3 and
      activate T cells reactive with lupus autoantigens. Using HLA-DR3 transgenic mice
      and lupus-associated autoantigen SmD protein, SmD(79-93) was identified to
      contain a dominant HLA-DR3 restricted T cell epitope. This T cell epitope was
      characterized by using a T-T hybridoma, C1P2, generated from SmD immunized HLA
      DR3 transgenic mouse. By pattern search analysis, 20 putative mimicry peptides
      (P2-P21) of SmD(79-93,) from microbial and human origin were identified. C1P2
      cells responded to SmD, SmD(79-93) and a peptide (P20) from Vibro cholerae.
      Immunization of HLA-DR3 mice with P20 induced T cell responses and IgG antibodies
      to SmD that were not cross-reactive with the immunogen. A T-T hybridoma, P20P1,
      generated from P20 immunized mice, not only responded to P20 and SmD(79-93), but
      also to peptides from Streptococcus agalactiae (P17) and human-La related protein
      (P11). These three T cell mimics (P20, P11 and P17) induced diverse and different
      autoantibody response profiles. Our data demonstrates for the first time
      molecular mimicry at T cell epitope level between lupus-associated autoantigen
      SmD and microbial peptides. Considering that distinct autoreactive T cell clones
      were activated by different microbial peptides, molecular mimicry at T cell
      epitope level can be an important pathway for the activation of autoreactive T
      cells resulting in the production of autoantibodies. In addition, the novel
      findings reported herein may have significant implications in the pathogenesis of
      SLE.

PMID- 21868198
TI  - Mini-implant insertion based on tooth crown references: a guide-free technique.
AB  - Mini-implant insertion requires accurate surgical technique. This study shows an
      insertion technique using only tooth crown references; its scientific basis is
      evaluated radiographically. The sample consisted of 213 inter-radicular septa,
      evaluated in 53 bitewing radiographs. The proximal contour of adjacent tooth
      crowns was used to define septum width. The midpoint of the septum width was
      linked to the interdental contact point to determine septum midline. The
      distances from septum midline to mesial and distal teeth were measured to
      evaluate the septum midline centralization degree in two different septum
      heights. The difference between mesial and distal distances represented the
      septum midline deviation degree. The mesial and distal distances were compared by
      t-tests, and the septum midline deviation was correlated with septum height using
      Pearson's correlation test. The mesial and distal distances were not
      statistically different in the midpoint of the septum height, but they were
      different at the apical septum height. There was a moderate correlation (r=0.45)
      between septum midline deviation and septum height. The tooth crown references
      evaluated on interproximal radiographs determine a high centralization degree of
      the septum midline on which the insertion site could be defined. The greater
      centralization degree was observed at the coronal septum area.

PMID- 21868200
TI  - Increasing mortality in schizophrenia: are women at particular risk? A follow-up
      of 1111 patients admitted during 1980-2006 in Northern Norway.
AB  - A study of mortality for all patients with schizophrenia admitted to the
      University Hospital of North Norway during 1980-2006 was performed, with a
      special focus on gender differences and changes in mortality during a period of
      transition from hospital-based to community-based care. A total of 1111 patients
      with schizophrenia were included, and the cohort was linked to the Causes of
      Death Register of Norway. Males and females had 3.5 and 2.6 times, respectively,
      higher mortality than the general population. The standardized mortality ratios
      were higher during the last nine years than the first nine years, and for women
      admitted after 1992, we found evidence for an increasing difference in mortality
      compared to the general female population as well as an increase in absolute
      mortality. In the subgroup of patients who had always been admitted voluntarily,
      women tended to have higher mortality, and a particularly high standardized
      mortality rate (SMR) was found in this group of female schizophrenic patients.
      Our results confirmed a persisting mortality gap between patients with
      schizophrenia and the general population over a period of 27 years, with a
      tendency of increasing standardized mortality ratios over time. The SMR for total
      mortality of women with schizophrenia is rising and becoming just as high as for
      men, both for unnatural and natural causes of death.

PMID- 21868201
TI  - Depth-of-processing effects on semantic activation deficits in schizophrenia: an
      electrophysiological investigation.
AB  - N400, an event-related brain potential (ERP) waveform elicited by meaningful
      stimuli, is normally reduced (made less negative) by relatedness between the
      eliciting stimulus and preceding ones (N400 semantic priming). Schizophrenia
      patients' N400 semantic priming deficits suggest impairment in using meaningful
      context to activate related concepts in semantic memory. We aimed to examine the
      degree to which this impairment can be ameliorated by task instructions that more
      explicitly require processing of stimulus meaning. We recorded ERPs from 16
      schizophrenia patients and 16 controls who viewed prime words each followed at
      750-ms stimulus-onset asynchrony by an unrelated or related target word, or a
      nonword, in a non-semantic task (indicating whether a letter occurred in the
      target) compared to an explicit semantic task (judging prime-target relatedness).
      Consistent with previous work, controls exhibited greater N400 semantic priming
      (larger amplitude reductions for related versus unrelated targets) in the
      semantic task than in the orthographic task. Schizophrenia patients showed this
      same pattern, although their N400 semantic priming effects were smaller than
      controls' across tasks. Nevertheless, patients' priming effects increased as much
      as did controls' from the orthographic to the semantic task. Thus, connections
      among related concepts in schizophrenia patients' semantic memory appear grossly
      intact, such that, given a meaningful stimulus, they can make use of explicit
      cues to activate related concepts at a neurophysiological level, although their
      ability to do so remains less than normal. These data provide support for further
      research on semantic-cueing strategies for cognitive remediation of verbal memory
      in schizophrenia.

PMID- 21868199
TI  - Distinct facial processing in schizophrenia and schizoaffective disorders.
AB  - Although schizophrenia and schizoaffective disorders have both similar and
      differing clinical features, it is not well understood whether similar or
      differing pathophysiological processes mediate patients' cognitive functions.
      Using psychophysical methods, this study compared the performances of
      schizophrenia (SZ) patients, patients with schizoaffective disorder (SA), and a
      healthy control group in two face-related cognitive tasks: emotion
      discrimination, which tested perception of facial affect, and identity
      discrimination, which tested perception of non-affective facial features.
      Compared to healthy controls, SZ patients, but not SA patients, exhibited
      deficient performance in both fear and happiness discrimination, as well as
      identity discrimination. SZ patients, but not SA patients, also showed impaired
      performance in a theory-of-mind task for which emotional expressions are
      identified based upon the eye regions of face images. This pattern of results
      suggests distinct processing of face information in schizophrenia and
      schizoaffective disorders.

PMID- 21868202
TI  - Differential patterns of CXCR3, CCR3, and CCR10 expression in mycosis fungoides,
      Sezary syndrome and CD30(+) lymphoproliferative disorders: immunohistochemical
      study of 43 samples.

PMID- 21868203
TI  - fMRI working memory hypo-activations in schizophrenia come with a coupling
      deficit between arousal and cognition.
AB  - Cognition has become a target for therapeutic intervention and favoring arousal
      could be a way to help patients. Working memory is an arousal dependent cognitive
      function. This study used functional MRI (fMRI) as a surrogate marker of working
      memory to evaluate the sensitivity of patients' hypoactive regions to arousal in
      a subpopulation of rehabilitated patients. Are hypoactive regions sensitive to
      arousal? Does the deficit result from arousal deficit or improper coupling with
      cognitive activity? Eighteen patients and matched controls were recruited.
      Participants performed a working memory task during combined
      electroencephalographic (EEG) and fMRI measurements. Cortical regions sensitive
      to arousal were defined as those which were inversely correlated with low EEG
      frequencies. Overlap between the arousal-sensitive and hypoactive regions was
      assessed by mutual information. Arousal-cognitive coupling was evaluated by the
      correlation between the arousal effect and the task effect. In the patient group,
      most hypoactive voxels were sensitive to arousal and corresponded to the
      prefronto-parietal network. But patients had no arousal deficit. Although arousal
      seems to improve cognitive activity in most of the patients' cortical areas, this
      coupling appears to be specifically disturbed in their hypoactive regions. In
      conclusion, although increasing arousal may help cognition, it may do so in an
      unspecific way.

PMID- 21868204
TI  - Preparation of magnetic modified chitosan and adsorption of Zn2+ from aqueous
      solutions.
AB  - The performance of a cross-linked magnetic modified chitosan (CMMC), which has
      been coated with magnetic fluids and cross-linked with glutaraldehyde, has been
      investigated for the adsorption of Zn(2+) from aqueous solutions. The CMMC with a
      diameter range of 20-50 nm was prepared. The effects of pH and the contact time
      for the adsorption have been discussed, and the optimal adsorption conditions for
      the adsorption of Zn(2+) have been obtained. The research results showed that
      CMMC was highly efficient for fast adsorption of Zn(2+) within the first 25 min,
      and adsorption equilibrium could be achieved in 30 min. Equilibrium studies
      showed that the data of Zn(2+) adsorption followed the Langmuir model. The
      maximum adsorption capacity for Zn(2+) was estimated to be 32.16 mg/g with a
      Langmuir adsorption equilibrium constant of 0.01 L/mg at 298 K, which
      demonstrated that the CMMC had obvious efficient adsorption of Zn(2+). The CMMC
      was stable and easily recovered. Moreover, the adsorption rate was about 90% of
      the initial saturation adsorption capacity after being used five times.

PMID- 21868205
TI  - Savinase action on bovine serum albumin (BSA) monolayers demonstrated with
      measurements at the air-water interface and liquid Atomic Force Microscopy (AFM)
      imaging.
AB  - We studied the enzymatic action of Savinase on bovine serum albumin (BSA)
      organized in a monolayer spread at the air/water interface or adsorbed at the
      mica surface. We carried out two types of experiments. In the first one we
      followed the degradation of the protein monolayer by measuring the surface
      pressure and surface area decrease versus time. In the second approach we applied
      AFM imaging of the supported BSA monolayers adsorbed on mica solid supports and
      extracted information for the enzyme action by analyzing the obtained images of
      the surface topography in the course of enzyme action. In both cases we obtained
      an estimate for the turnover number (TON) of the enzyme reaction.

PMID- 21868206
TI  - [Neonatal occlusion due to a lumbar hernia].
AB  - A Petit lumbar hernia is an uncommon hernia. Congenital forms are seen in
      children. Incarceration may occur as an unreducible lumbar mass, associated with
      bilious vomiting and abdominal distention. Abdominal X-ray shows sided-wall bowel
      gas. In this case, reduction and primary closure must be performed as emergency
      repair.

PMID- 21868207
TI  - [Evaluation of the glycemia of low-weight newborns within the 24th hour of life
      at Lome University Hospital (Togo)].
AB  - OBJECTIVE: To assess the glycemia of low-weight newborns (LWNBs) during their
      first 24h of life as well as their mother's glycemia. PATIENTS AND METHOD: This
      was a cross-sectional prospective study within a case-control group, conducted at
      Lome University Hospital (nationwide main hospital) from January to May 2006. One
      hundred thirty-nine LWNBs and 150 eutrophic term newborns (ETNBs), 98 mothers of
      LWNBs (MLWNBs), and 145 mothers of ETNBs (METNBs) were screened and monitored on
      glycemia dosage. RESULTS: The average glycemia level of the LWNBs (0.34 +/-
      0.27g/l) was significantly greater than the ETNBs' glycemia level (0.30 +/- 0.14
      g/l); it was nearly the same for the mean glycemia level of the MLWNBs (0.82 +/-
      0.2g/l) and the METNBs (0.77 +/- 0.1g/l). Neonatal hypoglycemia during the first
      24h of life was less frequent (RR=0.8) in the LWNBs (61.15%) than in the ETNBs
      (80%). The positive correlation between gestational age and glycemia was higher
      in the ETNBs (r=0.17) than in the LWNBs (r=0.07). This positive correlation
      between birthweight and glycemia was lower in the LWNBs (r=0.17) compared to the
      ETNBs (r=0.37); this was not the case within the group of the ETNBs (r=0.02)
      compared to the group of the LWNBs (r=0.34) concerning the correlation between
      the glycemia of mothers and newborns. CONCLUSION: The early hypoglycemia was much
      greater in the ETNBs compared to the LWNBs. Therefore, it is necessary to
      systematically start breastfeeding all newborns within their first hours of life
      whatever their gestational age, in order to solve these metabolic disorders.

PMID- 21868208
TI  - Classification of cancer cell death with spectral dimensionality reduction and
      generalized eigenvalues.
AB  - OBJECTIVE: Accurate cell death discrimination is a time consuming and expensive
      process that can only be performed in biological laboratories. Nevertheless, it
      is very useful and arises in many biological and medical applications. METHODS
      AND MATERIAL: Raman spectra are collected for 84 samples of A549 cell line (human
      lung cancer epithelia cells) that has been exposed to toxins to simulate the
      necrotic and apoptotic death. The proposed data mining approach for the
      multiclass cell death discrimination problem uses a multiclass regularized
      generalized eigenvalue algorithm for classification (multiReGEC), together with a
      dimensionality reduction algorithm based on spectral clustering. RESULTS: The
      proposed algorithmic scheme can classify A549 lung cancer cells from three
      different classes (apoptotic death, necrotic death and control cells) with
      97.78%+/- 0.047 accuracy versus 92.22 +/- 0.095 without the proposed feature
      selection preprocessing. The spectrum areas depicted by the algorithm corresponds
      to the >C O bond from the lipids and the lipid bilayer. This chemical structure
      undergoes different change of state based on cell death type. Further evidence of
      the validity of the technique is obtained through the successful classification
      of 7 cell spectra that undergo hyperthermic treatment. CONCLUSIONS: In this study
      we propose a fast and automated way of processing Raman spectra for cell death
      discrimination, using a feature selection algorithm that not only enhances the
      classification accuracy, but also gives more insight in the undergoing cell death
      process.

PMID- 21868209
TI  - Impaired health-related quality of life in pulmonary nontuberculous mycobacterial
      disease.
AB  - INTRODUCTION: The impact of pulmonary nontuberculous mycobacterial (pNTM) disease
      on health-related quality of life (HRQL) has not been quantified. METHODS: We
      performed a prospective observational study of HRQL in 51 patients with pNTM
      disease. One generic (Short-form 36, version 2 -SF-36), and one pulmonary disease
      specific instrument (St. George's Respiratory Questionnaire--SGRQ) were
      administered to each subject. RESULTS: Fifty-one patients with pNTM disease from
      one ambulatory clinic were enrolled. The mean (sd) age was 67 (10) years and 80%
      (41/51) were female. The most common causative NTM was MAC in 84% (43/51)
      followed by Mycobacterium abscessus in 8% (4/51). Radiographic disease type was
      nodular bronchiectasis in 71% (36/51) and fibrocavitary in 22% (11/51). For SF
      36, most raw scores were at least 10 points below Canadian population-based
      normals, and all normbased scores were below the expected normal value of 50. For
      SGRQ, all scores were worse by >= 25 points compared with published normals. In
      multivariable analyses, only FVC and DLCO were significantly associated with SF
      36, and only FVC and emphysema were significantly associated with SGRQ.
      CONCLUSION: Patients with pNTM disease have significantly impaired HRQL that is
      most closely associated with lung function and not readily explained by age, sex
      or extra-pulmonary comorbidity.

PMID- 21868211
TI  - The role of intergenerational influence in waste education programmes: the THAW
      project.
AB  - Whilst the education of young people is often seen as a part of the solution to
      current environmental problems seeking urgent attention, it is often forgotten
      that their parents and other household members can also be educated/influenced
      via home-based educational activities. This paper explores the theory of
      intergenerational influence in relation to school based waste education. Waste
      Watch, a UK-based environmental charity (www.wastewatch.org.uk), has pioneered a
      model that uses practical activities and whole school involvement to promote
      school based action on waste. This methodology has been adopted nationally. This
      paper outlines and evaluates how effective school based waste education is in
      promoting action at a household level. The paper outlines Waste Watch's 'Taking
      Home Action on Waste (THAW)' project carried out for two and half years in
      Rotherham, a town in South Yorkshire, England. The project worked with 6705
      primary age children in 39 schools (44% of primary schools in the project area)
      to enable them to take the "reduce, reuse and recycle message" home to their
      families and to engage these (i.e. families) in sustainable waste management
      practices. As well as substantial increases in students' knowledge and
      understanding of waste reduction, measurement of the impact of the project in
      areas around 12 carefully chosen sample schools showed evidence of increased
      participation in recycling and recycling tonnages as well as declining levels of
      residual waste. Following delivery of the project in these areas, an average
      increase of 8.6% was recorded in recycling set out rates which led to a 4.3%
      increase in paper recycling tonnages and an 8.7% increase in tonnages of cans,
      glass and textiles collected for recycling. Correspondingly, there was a 4.5%
      fall in tonnages of residual waste. Waste Watch's THAW project was the first
      serious attempt to measure the intergenerational influence of an education
      programme on behaviour at home (i.e. other than schools' own waste). It clearly
      shows that household recycling behaviour can be positively impacted by
      intergenerational influence via a practical school-based waste education model.
      However, although the model could potentially have a big impact if rolled out
      nationally, it will require seed funding and the long-term durability of the
      model has not yet been fully quantified.

PMID- 21868210
TI  - Short term effects of copper, sulfadiazine and difloxacin on the anaerobic
      digestion of pig manure at low organic loading rates.
AB  - Antibiotics of inorganic and organic origin in pig manure can inhibit the
      anaerobic process in biogas plants. The influence of three frequently used
      antibiotics, copper dosed as CuSO(4), sulfadiazine (SDZ), and difloxacin (DIF),
      on the anaerobic digestion process of pig manure was studied in semi-continuous
      experiments. Biogas production recovered after every Cu dosage up to a sum of
      12.94g Cukg(-1) organic dry matter (ODM), probably due to Cu precipitation
      following the formation of sulphide from sulphate. Complete inhibition was found
      at the very high Cu concentration of 19.40g Cukg(-1) ODM. Inhibitory effect of
      SDZ and DIF was observed at concentrations as high as 2.70gkg(-1) ODM and
      0.54gkg(-1) ODM, respectively. It seems very unlikely that the antibiotics tested
      would inhibit the anaerobic process in a full-scale biogas plant.

PMID- 21868212
TI  - "DNA-Dressed NAnopore" for complementary sequence detection.
AB  - Single molecule electrical sensing with nanopores is a rapidly developing field
      with potential revolutionary effects on bioanalytics and diagnostics. The recent
      success of this technology is in the simplicity of its working principle, which
      exploits the conductance modulations induced by the electrophoretic translocation
      of molecules through a nanometric channel. Initially proposed as fast and
      powerful tools for molecular stochastic sensing, nanopores find now application
      in a range of different domains, thanks to the possibility of finely tuning their
      surface properties, thus introducing artificial binding and recognition sites.
      Here we show the results of DNA translocation and hybridization experiments at
      the single molecule level by a novel class of selective biosensor devices that we
      call "DNA-Dressed NAnopore" (DNA(2)), based on solid state nanopore with large
      initial dimensions, resized and activated by functionalization with DNA
      molecules. The presented data demonstrate the ability of the DNA(2) to
      selectively detect complementary target sequences, that is to distinguish between
      molecules depending on their affinity to the functionalization. The DNA(2) can
      thus constitute the basis for the design of integrable parallel devices for
      mutation DNA analysis, diagnostics and bioanalytic investigations.

PMID- 21868213
TI  - Protein biomarker enrichment by biomarker antibody complex elution for
      immunoassay biosensing.
AB  - It is very challenging to perform sample enrichment for protein biomarkers
      because proteins can easily change conformation and denature. In this paper we
      demonstrate protein enrichment suited for high-sensitivity integrated immuno
      biosensing. The method enhances the concentration of the biomarkers and
      simultaneously removes matrix components that could interfere with the
      immunoassay. Biomarkers are captured using antibody coated magnetic particles and
      the biomarker antibody complexes are released by enzymatic elution. The eluted
      complexes are subsequently detected in a sandwich immunoassay biosensor. A
      scaling study of the enrichment process demonstrates an enrichment factor of 15
      in buffer and plasma. We analyze the enrichment factor in terms of the three
      basic steps of the assay (capture, concentration, elution) and we quantify their
      respective efficiencies. The process is suited for integration into bio
      analytical tools.

PMID- 21868215
TI  - Assessment of denitrifying bacterial composition in activated sludge.
AB  - The abundance and structure of denitrifying bacterial community in different
      activated sludge samples were assessed, where the abundance of denitrifying
      functional genes showed nirS in the range of 10(4)-10(5), nosZ with 10(4)-10(6)
      and 16S rRNA gene in the range 10(9)-10(10) copy number per ml of sludge. The
      culturable approach revealed Pseudomonas sp. and Alcaligenes sp. to be
      numerically high, whereas culture independent method showed betaproteobacteria to
      dominate the sludge samples. Comamonas sp. and Pseudomonas fluorescens isolates
      showed efficient denitrification, while Pseudomonas mendocina, Pseudomonas
      stutzeri and Brevundimonas diminuta accumulated nitrite during denitrification.
      Numerically dominant RFLP OTUs of the nosZ gene from the fertilizer factory
      sludge samples clustered with the known isolates of betaproteobacteria. The data
      also suggests the presence of different truncated denitrifiers with high numbers
      in sludge habitat.

PMID- 21868214
TI  - Regulation of the catalytic activity of the EGF receptor.
AB  - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase
      involved in cell growth that is often misregulated in cancer. Several recent
      studies highlight the unique structural mechanisms involved in its regulation.
      Some elucidate the important role that the juxtamembrane segment and the
      transmembrane helix play in stabilizing the activating asymmetric kinase dimer,
      and suggest that its activation mechanism is likely to be conserved among the
      other human EGFR-related receptors. Other studies provide new explanations for
      two long observed, but poorly understood phenomena, the apparent heterogeneity in
      ligand binding and the formation of ligand-independent dimers. New insights into
      the allosteric mechanisms utilized by intracellular regulators of EGFR provide
      hope that allosteric sites could be used as targets for drug development.

PMID- 21868216
TI  - Comparison of covalent immobilization of amylase on polystyrene pellets with
      pentaethylenehexamine and pentaethylene glycol spacers.
AB  - alpha-Amylase from Aspergillus oryzae was covalently immobilized onto polystyrene
      pellets with pentaethylenehexamine (PS-PEHA-Ald) and pentaethylene glycol (PS-PG
      Ald) carrying a terminal aldehyde group. Optimum immobilization occured at pH 8.0
      and 25  degrees C, and at pH 7.0 and 35  degrees C for PS-PEHA-Ald and PS-PG-Ald,
      respectively. PS-PEHA-Ald immobilized enzyme retained approximately 75% of the
      initial activity over 45 days of storage, 70% of the initial activity after nine
      runs of recycling and displayed the better resistance to detrimental metal ions.
      PS-PG-Ald immobilized enzyme retained approximately 50% of the initial activity
      in 8h at 70  degrees C. The catalytic efficiencies of PS-PEHA-Ald immobilized and
      PS-PG-Ald immobilized amylase were 1.42 and 1.29 times higher than that of native
      enzyme. The activation energy of the reaction mediated by the amylase was reduced
      by 58.1% and 57.3% when PS-PEHA-Ald and PS-PG-Ald used as support respectively.

PMID- 21868217
TI  - Characterization and dye decolorization ability of an alkaline resistant and
      organic solvents tolerant laccase from Bacillus licheniformis LS04.
AB  - A new bacterial strain exhibiting laccase activity was isolated from forest soil
      and was identified as Bacillus licheniformis LS04. The spore laccase of B.
      licheniformis LS04 demonstrated a broad pH range for catalyzing substrates. It
      was quite stable at high temperature and alkaline pH. There was no loss of
      laccase activity after 10 days incubation at pH 9.0, and about 16% of the initial
      activity was detected after 10h at 80 degrees C. In addition, the spore laccase
      was tolerant towards 1M of NaCl and 30% of organic solvents. Reactive black 5,
      reactive blue 19 and indigo carmine were decolorized by the spore laccase in the
      absence of mediator. Meanwhile, the decolorization process was efficiently
      promoted when acetosyringone was present, with more than 80% of color removal in
      1h at pH 6.6 or 9.0. The unusual properties indicated a high potential in
      industrial applications for this novel spore laccase.

PMID- 21868218
TI  - Mechanisms of enhanced cellulosic bioethanol fermentation by co-cultivation of
      Clostridium and Thermoanaerobacter spp.
AB  - Engineering microbial consortia capable of efficient ethanolic fermentation of
      cellulose is a strategy for the development of consolidated bioprocessing for
      bioethanol production. Co-cultures of cellulolytic Clostridium thermocellum with
      non-cellulolytic Thermoanaerobacter strains (X514 and 39E) significantly improved
      ethanol production by 194-440%. Strain X514 enhanced ethanolic fermentation much
      more effectively than strain 39E in co-cultivation, with ethanol production in
      X514 co-cultures at least 62% higher than that of 39E co-cultures. Comparative
      genome sequence analysis revealed that the higher ethanolic fermentation
      efficiency in strain X514 was associated with the presence of a complete vitamin
      B(12) biosynthesis pathway, which is incomplete in strain 39E. The significance
      of the vitamin B(12)de novo biosynthesis capacity was further supported by the
      observation of improved ethanol production in strain 39E by 203% following the
      addition of exogenous vitamin B(12). The vitamin B(12) biosynthesis pathway
      provides a valuable biomarker for selecting metabolically robust strains for
      bioethanol production.

PMID- 21868219
TI  - A new algorithm to characterize biodegradability of biomass during anaerobic
      digestion: influence of lignin concentration on methane production potential.
AB  - We examined the influence of fibrous fractions of biomass on biochemical methane
      potential (BMP) with the objective of developing an economical and easy-to-use
      statistical model to predict BMP, and hence the biodegradability of organic
      material (BD) for biogas production. The model was developed either for energy
      crops (grass, maize, and straw) or for animal manures, or as a combined model for
      these two biomass groups. It was found that lignin concentration in volatile
      solids (VS) was the strongest predictor of BMP for all the biomass samples. The
      square of the sample correlation coefficient (R(2)) from the BMP versus lignin
      was 0.908 (p<0.0001), 0.763 (p<0.001) and 0.883 (p<0.001) for animal manure,
      energy crops and the combined model, respectively. Validation of the combined
      model was carried out using 65 datasets from the literature.

PMID- 21868220
TI  - Exploration of pyridine containing heteroaryl analogs of biaryl ureas as DGAT1
      inhibitors.
AB  - The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential
      target for obesity as this enzyme is dedicated to the final committed step in
      triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been
      reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2
      pyridyl and 3-pyridyl containing biaryl ureas as hDGAT1 inhibitors. Our aim was
      to incorporate a heteroaryl scaffold within these molecules thereby improving the
      cLogP profile and making these compounds more drug-like. Compounds within this
      series exhibited potent hDGAT1 inhibition when evaluated using an in vitro
      enzymatic assay. Selected compounds were also subjected to an oral fat tolerance
      test in mice where the percent triglyceride reduction versus a vehicle control
      was evaluated. Of the studied heteroaryl analogs compound 44 exhibited an in
      vitro IC(50) of 17nM and a plasma triglyceride reduction of 79% along with a 12
      fold improvement in solubility over the biphenyl urea compound 4.

PMID- 21868221
TI  - Hydrazidomycins, cytotoxic alkylhydrazides from Streptomycesatratus.
AB  - Three unusual alkyhydrazide natural products, named hydrazidomycin A (1), B (2)
      and C (3), were isolated from the chloroform extract of a Streptomycesatratus
      culture, and their structures were elucidated by MS and NMR techniques.
      Hydrazidomycins A-C exhibited moderate to strong cytotoxic activities in a panel
      of 42 cell lines, with hydrazidomycin A being the most potent compound (mean
      IC(50)=0.37 MUM).

PMID- 21868222
TI  - Synthesis and in vitro antiprotozoal activities of 5
      phenyliminobenzo[a]phenoxazine derivatives.
AB  - A series of 5-phenyliminobenzo[a]phenoxazine derivatives were synthesized. The in
      vitro antiprotozoal activities were evaluated against Plasmodium falciparum K1,
      Trypanosoma cruzi, Leishmania donovani and Trypanosoma brucei rhodesiense. N,N
      Diethyl-5-((4-methoxyphenyl)imino)-5H-benzo[a]phenoxazin-9-amine shows
      IC(50)=0.040 MUmol L(-1) with a selective index of 1425 against Plasmodium
      falciparum K1.

PMID- 21868223
TI  - The lived ICU experience of nurses, patients and family members: a
      phenomenological study with Merleau-Pontian perspective.
AB  - AIM: To describe and understand the lived intensive care unit experience of
      nurses, patients and family members during critical illness. BACKGROUND: There is
      a paucity of research studies in the literature conducted on the triad of nurses,
      patients and family members looking at the experience of critical illness and
      their perspective of each, from the other. METHODOLOGY: A phenomenological
      approach and Merleau-Ponty's existentials of corporeality, temporality,
      relationality and spatiality was used for this study. In-depth, open-ended
      interviews were, conducted and analysed using van Manen's wholistic, selective
      and detailed line-by-line approach. RESULTS: Five common themes (a) and three
      specific themes (b) emerged from the data: (a) family as a, unit, physical
      care/comfort, physiological care, psychosocial support and transformation; and,
      (b) advocacy, uncertainty and confidence in the nurse and the healthcare team.
      CONCLUSION: Examining embodied experience of corporeality, temporality,
      spatiality and relationality, opens new ways for coping amongst patients and
      their families, as well as care giving possibilities for the, nurses. This study
      affirms the mutual influence amongst the family, patient and nurses during a
      critical, illness experience and supports the tenets of family-centred care,
      which mandates the purposeful, inclusion of the family in all aspects of their
      loved one's care.

PMID- 21868224
TI  - Intensive care nurses' knowledge of critical care family needs.
AB  - AIMS: To explore nurses' knowledge of family needs and to describe their current
      practices in meeting those needs. BACKGROUND: Accurately assessing and responding
      to family needs of critically ill patients is significant in reducing the
      negative impact of stress; strengthens the ability to interact positively;
      increases family satisfaction with care and promotes trust and confidence.
      Inadequate attention to complex family needs can result in care fragmentation,
      family alienation, and the development of adversarial relationships between
      families and care givers. METHODS: A descriptive correlational quantitative
      design was utilised for this study, with data collected over a three-month period
      from nurses working within an Intensive Care Unit. RESULTS: The majority of
      respondents (n=44) scored above 70% in their knowledge of the needs of family
      members, indicating an excellent knowledge of those needs but only 4.2% (n=2)
      were able to rank family needs in order of importance. Whilst nurses reported
      very good practices in relation to caring for relatives there was no significant
      statistical relationship found between knowledge scores and self-reported
      practice indicating that whilst they had the knowledge it is not necessarily
      translated into clinical practice. But 71.4% (n=34) of respondents claimed their
      knowledge came from clinical work in ICU and continuing education courses (42%).
      CONCLUSION: Nurses demonstrated a very good knowledge of the needs of relatives
      and reported effective nursing interventions in supporting those needs, but
      knowledge is not necessarily translated into practice.

PMID- 21868225
TI  - Balance assessments for predicting functional ankle instability and stable
      ankles.
AB  - A number of instrumented and non-instrumented measures are used to detect balance
      deficits associated with functional ankle instability (FAI). Determining outcome
      measures that detect balance deficits associated with FAI might assist clinicians
      in identifying impairments that may otherwise go undetected with less responsive
      balance measures. Thus, our objective was to determine the balance measure that
      best predicted ankle group membership (FAI or stable ankle). Participants
      included 17 subjects without a history of ankle sprains (168+/-9 cm, 66+/-14 kg,
      24+/-5 yr) and 17 subjects with FAI (172+/-9 cm, 71+/-11 kg, 22+/-3 yr). Balance
      trials were performed without vision and subjects stood on a single leg as
      motionless as possible for 20s. Balance was quantified with center-of-pressure
      measures (velocity, area) and error score. Measures were positively correlated
      with each other (r range: 0.60-0.76). The multifactorial model with all three
      measures best predicted group membership (F((3,30))=7.20, P=0.001; R(2)=0.42;
      percent classified correctly=77%), and was followed by the multifactorial model
      with resultant center-of-pressure velocity and error score (F((2,31))=8.73,
      P=0.001; R(2)=0.36; percent classified correctly=74%). The resultant center-of
      pressure velocity (F((1,32))=13.46, P=0.001; R(2)=0.30; percent classified
      correctly=74%; unique variance=12.7%) and error score (F((1,32))=12.51, P=0.001;
      R(2)=0.28; percent classified correctly=71%; unique variance=12.0%) predicted
      group membership; however, 95th percentile center-of-pressure area ellipse did
      not (F((1,32))=4.16, P=0.05; R(2)=0.12; percent classified correctly=65%; unique
      variance=5.8%). A multifactorial single leg balance assessment is best for
      predicting group membership. COPV is the best single predictor of group
      membership, but clinicians may use error score to identify deficits associated
      with FAI if force plates are not available.

PMID- 21868226
TI  - Is age or speed the predominant factor in the development of trunk movement in
      normally developing children?
AB  - BACKGROUND: Gait analysis is an increasingly used tool in the evaluation of
      neurological or orthopaedic problems in children. A good insight into age-related
      changes in normal paediatric gait is necessary to evaluate gait inefficiency
      caused by pathological walking patterns in children. However, no systematic
      evaluation of the normal development of trunk movement has yet been made.
      METHODS: Data of n=85 healthy children were available. They were asked to walk at
      self selected speed. The gait data were measured with the Vicon Plug-In-Gait
      model, including the trunk. We assessed gait cycles of thorax, spine and pelvis
      in the sagittal, frontal and transverse plane, respectively, stratified by age
      (categories: <4, 4-6, 7-9, 10-12 and 13-16 years) as well as by normalized speed
      (<= 0.40, 0.41-0.49, >= 0.50). RESULTS: The sagittal thorax and spine movement
      was found to be gradually and significantly associated with age, but less so with
      speed, indicating that, with increasing age, children tend to lean their trunk
      forward relative to both the global co-ordinate system and the pelvis. In
      contrast, the frontal and transverse parameters of spine and pelvic movement
      seemed to depend mainly on speed, not age. CONCLUSION: Our study shows that age
      dependency has to be considered with respect to sagittal thorax and spine
      movements. This finding might be of great importance with respect to the
      identification of pathological patterns in trunk movement.

PMID- 21868227
TI  - Comparison of cerebral activation involved in oral and manual stereognosis.
AB  - Brain activity associated with manual stereognosis has been the focus of
      increasing recent research effort. However, although oral stereognosis, defined
      as the ability to recognize and discriminate the food bolus in the mouth, is
      important for mastication and swallowing, there is little information available
      about the neural network relating to this function. In the present study,
      cerebral activation associated with oral stereognosis was evaluated as compared
      with manual stereognosis. Brain imaging data were acquired by functional MRI
      (fMRI). fMRI experiments were performed on 16 healthy right-handed young adults
      without any history of neurological or psychiatric disorders. All subjects had
      all teeth without malocclusion. Ten stereognosis test shape pieces sized
      approximately 20 mm * 20 mm * 10 mm were fabricated for this experiment. All test
      pieces had a complicated form that made them difficult to recognize with ease.
      Subjects were instructed to assess the shape of the test piece in the mouth or
      hand. The ten test pieces were randomly assigned to each subject and each run.
      Stereognosis-specific activation was found in the primary somatosensory area,
      primary motor area, supramarginal gyrus, premotor area, supplementary motor area,
      fusiform gyrus, frontopolar area and dorsolateral prefrontal cortex. Differences
      in cerebral activation between oral and manual stereognosis were found in the
      insular cortex and visual association cortex.

PMID- 21868228
TI  - Carpal tunnel syndrome secondary to an osteophyte of the trapezium.
AB  - We report a 42-year-old man with a rare carpal tunnel syndrome (CTS) secondary to
      an osteophyte of the trapezium. The patient presented with a 3-year history of
      CTS, consisting of progressive pain and paresthesias in his right hand, positive
      Tinel and Phalen signs, and an electrodiagnostic study demonstrating median nerve
      compression at the wrist. The procedure was an open carpal tunnel release.
      Intraoperatively, a bony protuberance was found beneath the transverse carpal
      ligament (TCL), resulting in compression of the median nerve. The median nerve
      was decompressed and the patient's symptoms resolved postoperatively. Surgical
      pathology revealed bony fragments, and a postoperative CT scan was supportive of
      an osteophytic remnant protruding from the trapezium. Carpal bone osteophytes are
      rarely reported causes of CTS.

PMID- 21868229
TI  - Minimally invasive lateral extracavitary resection of foraminal neurofibromas.
AB  - Nerve sheath tumors are the most common spinal tumors but extradural foraminal
      nerve sheath tumors are much rarer. Traditionally, these nerve sheath tumors have
      been resected via an open posterior approach. We describe an alternative
      minimally invasive (MIS) lateral extracavitary approach for resection of
      symptomatic extradural foraminal spinal neurofibromas. We describe three
      consecutive male patients (mean age, 37 years) who underwent a successful MIS
      lateral extracavitary approach for surgical resection of symptomatic extradural
      spinal neurofibromas. All patients presented with pain and two of the three
      presented with neurological deficit. Follow-up data, including functional and
      radiographic outcomes, were collected for all patients. The mean operative time,
      blood loss, and length of stay were 85 minutes (min) (range, 60-120 min), 150 mL
      (range, 100-200 mL), and two days (range, 1-3 day), respectively. There were no
      complications. All patients had complete resolution of their pain and motor
      deficits. Thus, the MIS lateral extracavitary approach is a safe and feasible
      alternative for resection of spinal extradural foraminal neurofibromas.

PMID- 21868230
TI  - Current strategies in the surgical management of cerebral metastases: an evidence
      based review.
AB  - Metastatic tumours are the most common form of cerebral neoplasm, occurring in up
      to 40% of patients with systemic cancer. Although the presence of metastatic
      disease portends limited survival, aggressive management of cerebral metastases
      is vital to preventing death from neurological causes and prolonging functional
      independence. Due to advancement in neurosurgical techniques and the advent of
      stereotactic radiosurgery as a non-operative alternative, current decision making
      for selecting the appropriate local treatment often results in clinical
      equipoise. In addition, the traditional blanket application of whole brain
      radiation has come under scrutiny as new evidence regarding the deleterious
      neurocognitive effects of ionizing radiation emerges. The completion of a series
      of randomized studies comparing the efficacy of surgery, radiosurgery, whole
      brain radiotherapy and various combined approaches for cerebral metastases in
      recent years has shed important light on addressing some of these issues. The
      focus of this review is to summarize the key findings and outline a practical
      approach for the management of cerebral metastases.

PMID- 21868231
TI  - Gliomatosis cerebri in a patient with Ollier disease.
AB  - Gliomatosis cerebri (GC) is an uncommon brain tumour defined as a diffuse
      neoplastic glial cell infiltration of the brain, involving more than two cerebral
      lobes and, occasionally, the infratentorial structures or the spinal cord. GC of
      the oligodendroglial phenotype is extremely rare, especially in the paediatric
      setting. We describe an unusual case of oligodendroglial GC diagnosed in a 16
      year-old boy with Ollier disease. To our knowledge this is the first case of GC
      reported in a child with Ollier disease.

PMID- 21868232
TI  - Polyethylene glycol (PEG) hydrogel dural sealant and collagen dural graft matrix
      in transsphenoidal pituitary surgery for prevention of postoperative
      cerebrospinal fluid leaks.
AB  - Cerebrospinal fluid (CSF) rhinorrhea is the most common complication after
      transsphenoidal pituitary surgery. The authors compare their previous experience
      using an autologous fat graft and lumbar drain placement in 107 patients with
      their current technique of using a dural sealant and collagen matrix in 97
      patients to prevent postoperative CSF leak after pituitary tumor resection. The
      failure rate for CSF leak repairs between the two groups was similar. The use of
      a dural sealant and collagen matrix, however, has the advantages of decreased
      length of hospital stay, decreased length of Intensive Care Unit stay, avoidance
      of the morbidity of an extra abdominal incision, and avoidance of the risks of
      lumbar CSF drainage.

PMID- 21868233
TI  - Relapse of primary central nervous system lymphoma 13 years after high-dose
      methotrexate-based polychemotherapy.
AB  - We report a now 74-year-old patient who was successfully treated with a
      methotrexate (MTX)-ssbased polychemotherapy protocol (Bonn protocol) for primary
      central nervous system lymphoma (PCNSL) in 1996. When presenting with an
      unusually late relapse after 13 years of tumor-free survival the diagnosis was
      made on the basis of clinical and radiological criteria. In the context of the
      very limited treatment options for recurrent PCNSL, it is reassuring that the re
      application of high dose-MTX-based polychemotherapy, including intraventricular
      treatment, again succeeded in a sustained complete response with still low
      neurotoxicity.

PMID- 21868234
TI  - Treatment strategy for chondromyxoid fibroma of the sacrum.
AB  - We present a 59-year-old woman with a rare sacral chondromyxoid fibroma
      discovered incidentally and treated with curettage, bone grafting, and
      lumbopelvic fixation. At 1 year following surgery she remains symptom-free, has
      successfully fused her lumbopelvic construct and has no signs of tumor
      progression. The known literature contains only six previous reports of sacral
      chondromyxoid fibroma and discussion is presented on the diagnosis and treatment
      of this rare lesion.

PMID- 21868235
TI  - A probable cavernoma in the medulla oblongata presenting only as upbeat
      nystagmus.
AB  - A cavernoma is a vascular malformation in the central nervous system. Brainstem
      cavernoma are relatively common and induce variable neurological symptoms. A 19
      year-old woman visited our hospital with complaints of continuous dizziness. On a
      neurological examination, continuous conjugated upbeat nystagmus was observed in
      the primary position of gaze. A brain CT scan and MRI showed focal hemorrhagic
      signals in the central caudal medulla caused by a cavernoma. The spontaneous
      upbeat nystagmus disappeared gradually. To our knowledge, this is the first
      report of a probable cavernoma in the medulla oblongata presenting with upbeat
      nystagmus only.

PMID- 21868236
TI  - Rapidly progressive lumbar subdural empyema following acromial bursal injection.
AB  - Spinal subdural empyemas are rare. We describe a 53-year-old male who presented
      with back pain, mental status changes, and sepsis. Five days prior he had
      undergone a triamcinolone and lidocaine injection of the acromial bursa. He also
      had a remote history of epidural steroid injection for thoracic back pain. Two
      lumbar MRI conducted 62 hours apart revealed a newly developed subdural empyema
      that was successfully treated with surgical evacuation and post-operative
      antibiotics.

PMID- 21868237
TI  - Single time angular deformity correction and treatment of knee instability in
      congenital fibular hemimelia. A case report.
AB  - BACKGROUND: Fibular hemimelia is the most frequently occurring congenital anomaly
      of long bones. These patients, among other deficiencies, have a poor development
      of the anterior cruciate ligament (ACL). Unless it causes clinically assessed
      instability of the knee, nonsurgical treatment is given. When surgical treatment
      is required, correction of angular limb deformity must be realized prior to ACL
      reconstruction. METHODS: We present the case of a 16-year old patient with
      congenital fibular hemimelia. Physical examination showed genu valgum,
      anteromedial rotatory instability and recurvatum of the right knee. We decided to
      perform surgical correction of the angular deformities and ACL reconstruction in
      the same surgical time. RESULTS: Twelve months after surgery, the patient had no
      evidence of clinical instability, with a range of motion from -5 degrees -110
      degrees  of the right knee. No claudication or gait instability was found. The KT
      1000 arthrometer showed a difference of 2mm between both knees. CONCLUSION: The
      ACL reconstruction and corrective osteotomies of angular deformities performed in
      a single surgical procedure had a good clinical result in a 12 month follow up
      period, restoring stability of the knee and allowing a normal gait cycle.

PMID- 21868238
TI  - Male subjects with early-stage knee osteoarthritis do not present biomechanical
      alterations in the sagittal plane during stair descent.
AB  - Patients with osteoarthritis (OA) of the knee show a loss of functional
      independence due to difficulty performing tasks that require high demand of the
      knee joint, such as descending stairs. However, it is unclear how muscular and
      biomechanical changes were present in patients with OA in the early stages. Thus,
      the purpose of this study was to analyze the kinetics, kinematics and muscle
      activation of men with early-stage knee OA during stair descent and compare them
      with a healthy control group. We evaluated 31 volunteers who were divided into
      two groups. The Osteoarthritis Group (OAG) included 17 men with grade I or II
      knee OA (53 +/- 6 years) and the Control Group (CG) included 14 healthy men (50
      +/- 6 years). We performed a kinematic evaluation of stair descent in the
      sagittal plane in order to analyze knee flexion angles. Electromyography (EMG) of
      the vastus lateralis muscle was also performed and the vertical ground reaction
      force was measured. The WOMAC questionnaire was administered to all volunteers.
      Statistical analysis consisted of the nonparametric Mann-Whitney U test for
      intergroup comparisons of all variables (p>0.05). There were no significant
      kinematic, kinetic or EMG differences between groups. For the WOMAC, the
      intergroup differences were significant in all three sections (pain: p=0.001,
      stiffness: p=0.008 and function: p=0.0005). In men with knee OA grade I or II,
      the stair decent is preserved in the sagittal plane, indicating that at these
      stages of the disease the functional adaptations are not expressed.

PMID- 21868239
TI  - Novel macrocyclic C-aryl glucoside SGLT2 inhibitors as potential antidiabetic
      agents.
AB  - Novel macrocyclic C-aryl glucoside SGLT2 inhibitors were designed and
      synthesized. Two different synthetic routes of macrocyclization were adopted to
      prepare novel ansa SGLT2 inhibitors. Among the compounds tested,
      [1,7]dioxacyclopentadecine macrocycles possessing methylthiophenyl at the distal
      ring 40 or ethoxyphenyl at the distal ring 23 showed the best in vitro inhibitory
      activity in this series to date (40, IC(50)=0.778 nM and 23, IC(50)=0.899 nM)
      against hSGLT2.

PMID- 21868240
TI  - Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases
      and atypical protein kinase C.
AB  - Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical
      balance between ceramide and sphingosine-1-phosphate. Much effort has been
      dedicated to develop inhibitors against these enzymes. Naturally occurring
      pachastrissamine (jaspine B) and all its stereoisomers were prepared and
      evaluated for their inhibitory effects against SphKs. All eight stereoisomers
      exhibited moderate to potent inhibitory activity against SphK1 and SphK2.
      Inhibitory effects were profiled against protein kinase C (PKC) isoforms by in
      vitro experiments. Atypical PKCs (PKCzeta and PKCiota) were inhibited by several
      pachastrissamine stereoisomers. The improved activity over N,N
      dimethylsphingosine suggests that the cyclic scaffold in pachastrissamines
      facilitates potential favorable interactions with SphKs and PKCs.

PMID- 21868242
TI  - A practical method for in-situ thickness determination using energy distribution
      of beta particles.
AB  - This paper discusses a method to determine the thickness of an absorber using the
      energy distribution of beta particles. An empirical relationship was obtained
      between the absorber thickness and the energy distribution of beta particles
      transmitted through. The thickness of a polyethylene radioactive source cover was
      determined by exploiting this relationship, which has largely been left
      unexploited allowing us to determine the in-situ cover thickness of beta sources
      in a fast, cheap and non-destructive way.

PMID- 21868241
TI  - Synthesis and biological evaluation of a peptide-paclitaxel conjugate which
      targets the integrin alphavbeta6.
AB  - The integrin alpha(v)beta(6) is an emergent biomarker for non-small cell lung
      cancer (NSCLC) as well as other carcinomas. We previously developed a tetrameric
      peptide, referred to as H2009.1, which binds alpha(v)beta(6) and displays minimal
      affinity for other RGD-binding integrins. Here we report the use of this peptide
      to actively deliver paclitaxel to alpha(v)beta(6)-positive cells. We synthesized
      a water soluble paclitaxel-H2009.1 peptide conjugate in which the 2'-position of
      paclitaxel is attached to the tetrameric peptide via an ester linkage. The
      conjugate maintains its specificity for alpha(v)beta(6)-expressing NSCLC cells,
      resulting in selective cytotoxicity. Treatment of alpha(v)beta(6)-positive cells
      with the conjugate results in cell cycle arrest followed by induction of
      apoptosis in the same manner as free paclitaxel. However, initiation of apoptosis
      and the resultant cell death is delayed compared to free drug. The conjugate
      demonstrates anti-tumor activity in a H2009 xenograft model of NSCLC with
      efficacy comparable to treatment with free paclitaxel.

PMID- 21868243
TI  - Half-life measurement of 66Ga with gamma-spectroscopy.
AB  - The half-life of (66)Ga, an isotope very important for high-energy efficiency
      calibration of gamma-detectors, has been measured using gamma-spectroscopy. In
      order to reduce systematic uncertainties, different source production methods and
      gamma-counting conditions have been applied. A half-life value of t(1/2)=(9.312+/
      0.032)h has been obtained in agreement with a recent measurement but in
      contradiction with some of the earlier results.

PMID- 21868244
TI  - Rapid changes in leaf elongation, ABA and water status during the recovery phase
      following application of water stress in two durum wheat varieties differing in
      drought tolerance.
AB  - This study aims to investigate the role of Abscisic acid (ABA) in water potential
      and turgor variations as well as growth recovery during the first phase of a
      rapid water stress induced by PEG6000. Two wheat varieties (Triticum durum L.),
      MBB (more tolerant) and OZ (less productive under drought), were grown in aerated
      nutrient solutions. Leaf elongation kinetics of the growing leaf 3 was estimated
      using LVDT. Water potential was measured using a pressure chamber; osmotic
      potential was estimated from expressed sap of elongation zone, turgor pressure of
      the same zone of leaf three was estimated directly by pressure probe. Growth
      rapidly ceased for a period of about one hour after the addition of PEG, gradual
      recovery was then observed for about 2 h. A significant difference was found in
      the % recovery of Leaf Elongation Rate (LER) and ABA between the two varieties,
      leading to better water status in MBB compared to OZ. The results of this study
      showed the possible role of ABA on growth resumption by the increase of relative
      water content and turgor via osmotic adjustment during the stress period in the
      leaves, which indicates the importance of OA in the resumption of LER even in the
      short term under conditions of water deficit. Full recovery of turgor but not of
      LER at the end stress period suggested the possible effect on cell wall
      extensibility (hardening) even at short term resulting from the rapid
      accumulation of ABA.

PMID- 21868245
TI  - Primary gastric cancer in an oesophageal gastric graft after oesophagectomy.
AB  - OBJECTIVE: Recent advances in surgical treatment of oesophageal cancer have
      improved the prognosis of early, locally advanced oesophageal cancer. Primary
      cancer from oesophageal graft is rare, but has been detected in long-term
      survivor. We analyzed data from patients who developed primary gastric cancer in
      an oesophageal graft to evaluate strategies of treatment and their outcomes.
      METHODS: We retrospectively reviewed data from patients who developed primary
      gastric cancer in oesophageal graft at Samsung Medical Center between September
      1994 and December 2009. The clinico-pathologic features and prognoses were
      investigated. Long-term survival rate was determined by Kaplan-Meier analysis.
      RESULTS: Ten primary gastric graft cancers (five early gastric cancer (EGC), five
      advanced gastric cancer (AGC)) were diagnosed. The mean age was 69.0 (range 59.6
      74.6). Initial operation was Ivor-Lewis transthoracic oesophagectomy in eight
      cases and three-field lymphadenectomy in two. The median period to detection of
      the primary gastric graft cancer after oesophagectomy was 50 (9-102) months.
      Seven gastric graft cancers were diagnosed by regular endoscopic examination.
      EGCs were treated with ESD in two cases, partial resection of stomach in one, and
      oesophagocolojejunostomy in three, including one patient who underwent the
      operation after ESD. AGCs were treated with chemotherapy in one case, supportive
      care in one, and oesophagocolojejunostomy in three. There was no adjuvant
      chemotherapy used in any case. The median follow-up period after second operation
      was 14 months (range 1-97). Six patients survived during this period. Three of
      the five AGC patients died. The estimated 5-year survival rate of our cases was
      70%. CONCLUSIONS: In areas of high prevalence of stomach cancer, regular
      endoscopic examinations of oesophageal gastric grafts may help in the early
      detection of primary gastric graft cancer. Reoperation with a colon graft is a
      potential treatment option for primary gastric graft cancer.

PMID- 21868247
TI  - Current development in regulation of similar biotherapeutic products in Brazil.
AB  - Because of the recent expiry of a large number of patents on the originator
      biological products, interest in the production and marketing of similar
      biotherapeutic products in Brazil has been increasing. The national producers
      have significant interest in this market and have been making a large amount of
      investments in these kinds of products. Since biotherapeutic products consume a
      large amount of the government health budget, the Brazilian government also has a
      big interest in the possibility that more affordable biotherapeutic products
      could be introduced into the market to improve access, but always is concerned
      with the quality, safety and efficacy of these products Accordingly, it was
      necessary to review the biological product regulations in Brazil and to establish
      specific pathways to license similar biotherapeutic products. The new Brazilian
      regulations, Resolution no. 55/2010, are based on different regulations and
      guidelines from around the world, including the WHO SBP Guidelines. They follow
      the same scientific principles as the WHO Guidelines but also have some
      differences which are due to specific country needs.

PMID- 21868246
TI  - Osteosarcomas of the mandible: are they different from other tumor sites?
AB  - BACKGROUND: Osteosarcomas of the mandible (MOS) affect 1/10 million persons/year,
      mostly the young adult. Due to lack of specific data, the treatment of MOS is
      extrapolated from that of extragnathic OS but varies widely between institutions.
      MATERIALS AND METHODS: We aimed at providing a focused description of MOS
      histologies and grades through the English literature, at determining the
      evidence-based role of chemotherapy, of adjuvant radiation therapy and the
      potential of reconstructive surgery tailored through modern pre-operative multi
      modal imaging. RESULTS: The estimated proportion of high grade MOS was 58%.
      However, low-grade MOS may be underestimated as they are mostly reported as case
      reports. The intermediate grade was hardly found in the literature. Estimated
      weighted-mean proportions of chondroblastic and osteoblastic MOS were 37% and
      46%, respectively. Multimodal imaging modalities including MRI has a great
      potential for accurate pre-operative assessment of tumor extensions into bone and
      soft tissues. Surgery is the mainstay of treatment and margins the most important
      factor. The role of neoadjuvant chemotherapy in treating occult systemic
      metastases and in increasing the probability of clear margins is controversial,
      as well as the histology-dependent response to chemotherapy. The role of adjuvant
      radiotherapy (mostly proposed for positive margins) and/or adjuvant chemotherapy
      is still controversial. Crude survival is around 77% and local control around
      67%. Local failure is the main cause of death in MOS compared to extragnathic
      sites.

PMID- 21868249
TI  - Anesthesia for thoracic surgery: a survey of UK practice.
AB  - OBJECTIVE: The authors sought to provide a snapshot of contemporary thoracic
      anesthetic practice in the United Kingdom and Ireland. DESIGN: An online survey.
      SETTING: United Kingdom. PARTICIPANTS: An invitation to participate was e-mailed
      to all members of the Association of Cardiothoracic Anaesthetists. INTERVENTION:
      None. MEASUREMENTS AND MAIN RESULTS: A total of 132 responses were received; 2
      were excluded because they did not originate from the United Kingdom. Values are
      number (percent). ANESTHETIC TECHNIQUE: The majority of respondents (109, 85%)
      maintain anesthesia with a volatile anesthetic agent, with a lesser proportion
      (20, 15%) reporting use of a total intravenous anesthetic technique. The majority
      of respondents (78, 61%) favor pressure control ventilation over volume control
      (50, 39%); just under half (57, 45%) report the routine use of positive end
      expiratory pressure (median = 5 cmH(2)O [interquartile range (IQR), 4-5]). Fifty
      two (40%) respondents report ventilating to a target tidal volume (median = 6
      mL/kg [IQR, 5-7]). Most (114, 89%) respondents routinely ventilate with an
      F(I)O(2) less than 1.0. Thoracic epidural blockade (TEB) is favored by nearly two
      thirds of respondents (80, 62%) compared with paravertebral block (39, 30%) and
      other analgesic techniques (10, 8%). Anesthesiologists favoring TEB are
      significantly less likely to prescribe systemic opioids (17, 21% v 39, 100% [p <
      0.001]). Proponents of TEB are significantly more likely to "routinely" use
      vasopressor infusions both intra- and postoperatively (16, 20% v 0, 0% [p =
      0.003] and 28, 35% v 4, 11% [p =0.013], respectively). Most respondents (127,
      98%) report a double-lumen tube as their first choice. Many (82, 64%) report
      "rarely" using bronchial blockers. CONCLUSIONS: The authors hope this survey both
      provides interest and serves as a useful resource reflecting the current practice
      of thoracic anesthesia.

PMID- 21868248
TI  - Intimate partner violence/abuse and depressive symptoms among female health care
      workers: longitudinal findings.
AB  - Intimate partner violence and abuse (IPV/A) have been shown to have a major
      impact on mental health functioning. This study assessed the longitudinal
      association between recent IPV/A and depressive symptoms to identify potential
      targets for preventive interventions for women. Random effects models were used
      to examine four waves of data collected at 6-month intervals from a cohort of
      1,438 female health care workers. IPV/A (e.g., sexual and physical violence,
      psychological abuse) in the past 5 years was associated with higher Center for
      Epidemiologic Studies Depression Scale (CES-D) 10 scores across four waves after
      adjustment for age, time, marital status, and childhood trauma. Women who
      reported IPV/A in the past 5 years had higher CES-D 10 scores (beta, 1.31; 95%
      confidence interval, 0.79-1.82; p < .0001) than nonabused women. This association
      was generally constant with time, suggestive of a cross-sectional association
      across all four waves of data. Additionally, recent IPV/A was associated with
      change in depressive symptoms over time among the full cohort and those with CES
      D 10 scores below 10 (the threshold for likely depression) at baseline. Recent
      IPV/A was independently associated with depressive symptoms both cross
      sectionally and longitudinally. The longitudinal association was stronger among
      those not depressed at baseline. Implications for health care settings and
      workplace policies addressing IPV/A are discussed.

PMID- 21868250
TI  - Management of cardiac tamponade after cardiac surgery.

PMID- 21868251
TI  - Feasibility of measuring renal blood flow using transesophageal echocardiography
      in pediatric patients undergoing cardiac surgery.
AB  - OBJECTIVE: To evaluate the feasibility of measuring renal blood flow (RBF) using
      transesophageal echocardiography (TEE) in pediatric patients undergoing cardiac
      surgery. DESIGN: A prospective noninterventional study. SETTING: A university
      hospital. PARTICIPANTS: Twenty-three pediatric patients who underwent surgical
      repair for complex congenital heart defects were included in this study.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The authors evaluated the
      accuracy of using TEE to visualize the left renal artery by comparing TEE images
      with preoperative computed tomography angiographic images. RBF was measured
      during the cardiopulmonary bypass (CPB) period. TEE images and Doppler studies
      from all subjects were interpreted by 2 blinded independent assessors. Inter- and
      intraobserver reproducibility was quantified by calculating the variability and
      intraclass correlation coefficients. Linear regression models were used to
      further investigate the relationship between volumetric RBF and CPB perfusion
      rate. The left renal artery was indentified successfully in 96% of the study
      population, with a mean Doppler angle of 19.5 degrees  +/- 6.7 degrees  (all of
      them <30 degrees ). Both inter- and intraobserver variability was <10%. Inter-
      and intraobserver reproducibility in the RBF measurements were excellent. The
      volumetric RBF showed a linear relationship with the CPB perfusion rate (r =
      0.881, p < 0.001) and the mean artery pressure (r = 0.457, p = 0.032).
      CONCLUSION: For 96% of pediatric patients undergoing cardiac surgery, it is
      feasible to measure RBF using intraoperative TEE during CPB. Volumetric RBF was
      related to the perfusion rate and the mean artery pressure during CPB.

PMID- 21868252
TI  - Preconditioning with repeated hyperbaric oxygen induces myocardial and cerebral
      protection in patients undergoing coronary artery bypass graft surgery: a
      prospective, randomized, controlled clinical trial.
AB  - OBJECTIVES: To evaluate the cerebral and myocardial protective effects of
      hyperbaric oxygen preconditioning in both on-pump and off-pump coronary artery
      bypass graft surgery. DESIGN: A prospective, randomized, single-blinded study
      including patients scheduled for elective on-pump or off-pump surgery between
      December 2007 and February 2009. SETTING: A tertiary care university teaching
      hospital. PARTICIPANTS: Forty-nine elective on-pump or off-pump coronary artery
      bypass graft surgery patients. INTERVENTIONS: Patients were randomized to either
      the control (15 patients with on-pump procedure and 10 patients with off-pump
      procedure, respectively) or hyperbaric oxygen (HBO; 14 patients with on-pump
      procedure and 10 patients with off-pump procedure, respectively) groups. Patients
      in the HBO groups underwent preconditioning for 5 days before surgery.
      MEASUREMENTS AND MAIN RESULTS: On-pump coronary artery bypass graft surgery
      patients preconditioned with HBO had significant decreases in S100B protein,
      neuron-specific enolase, and troponin I perioperative serum levels compared with
      the on-pump control group. Postsurgically, patients in the on-pump HBO group had
      a reduced length of stay in the intensive care unit and a decreased use of
      inotropic drugs. Serum catalase activity 24 hours postoperatively was
      significantly increased compared with the on-pump control group. In the off-pump
      groups, there was no difference in any of the same parameters. CONCLUSIONS:
      Preconditioning with HBO resulted in both cerebral and cardiac protective effects
      as determined by biochemical markers of neuronal and myocardial injury and
      clinical outcomes in patients undergoing on-pump coronary artery bypass graft
      surgery. No protective effects were noted in off-pump coronary artery bypass
      graft surgery.

PMID- 21868254
TI  - Methodological vs. strategic control in artificial grammar learning: A commentary
      on Norman, Price and Jones (2011).
AB  - Norman et al. (2011) reported that participants exposed in succession to two
      artificial grammars could be able to learn implicitly about them, and could apply
      their knowledge strategically to select which string corresponds to one of these
      two grammars. In this commentary, I identify an artifact that could account for
      the learning obtained not only in this study, but also in some previous studies
      using the same procedures. I claim that more methodological control is needed
      before jumping to conclusions on the kind of strategic control that could be
      achieved unconsciously.

PMID- 21868253
TI  - Effects of a percutaneous mechanical circulatory support device for medically
      refractory right ventricular failure.
AB  - BACKGROUND: Medically refractory right ventricular failure (MR-RVF) is associated
      with high in-hospital mortality and is managed with surgical assist devices,
      atrial septostomy, or extracorporeal membrane oxygenation. This study explored
      the hemodynamic effect associated with a percutaneous RV support device (pRVSD)
      for MR-RVF. METHODS: Between 2008 and 2010, 9 patients with MR-RVF, defined as
      cardiogenic shock despite maximal medical therapy, were treated with a pRVSD.
      Medical records were reviewed for demographics, hemodynamic and laboratory data,
      and details of pRVSD implantation. RESULTS: MR-RVF was due to severe sepsis in 1
      patient (11.1%), post-cardiotomy syndrome in 2 (22.2%), and acute inferior wall
      myocardial infarction (IWMI) in 6 (66.7%). Five patients underwent right internal
      jugular-to-femoral cannulation, and 4 required bifemoral cannulation. No intra
      procedural deaths or major vascular complications requiring surgical or
      peripheral intervention occurred. Time from admission to pRVSD implantation was
      2.9 +/- 3.3 days, with an average of 6516 +/- 698 rotations/min, providing flow
      at 3.3 +/- 0.4 liters/min. Mean duration of pRVSD activation was 3.1 +/- 1.8
      days. Compared with pre-procedural values, mean arterial pressure (57 +/- 7 vs 75
      +/- 19 mm Hg, p < 0.05), right atrial pressure (22 +/- 3 vs 15 +/- 6 mm Hg, p <
      0.05), cardiac index (1.5 +/- 0.4 vs 2.3 +/- 0.5 liters/min/m(2), p < 0.05),
      mixed venous oxygen saturation (40 +/- 14 vs 58 +/- 4 percent, p < 0.05), and RV
      stroke work (3.4 +/- 3.9 vs 9.7 +/- 6.8 g . m/beat, p < 0.05) improved
      significantly within 24 hours of pRVSD implantation. In-hospital mortality was
      44% (n = 4). Time from admission to pRVSD placement was lower in patients who
      survived to hospital discharge (0.9 +/- 0.8 days) vs non-survivors (4.8 +/- 3.5
      days; p = 0.04). All survivors presented with IWMI. CONCLUSION: Use of a pRVSD
      for MR-RVF is feasible and associated with improved hemodynamics. Algorithms
      promoting earlier pRVSD use in MR-RVF warrant further investigation.

PMID- 21868256
TI  - The effect of implant malalignment on joint loading in total elbow arthroplasty:
      an in vitro study.
AB  - HYPOTHESIS: Aseptic loosening is one of the leading causes of failure in total
      elbow arthroplasty. Incorrect implant positioning and alignment in other joints
      such as the knee have been found to lead to excessive loading and wear. Although
      similar alignment difficulties exist in the elbow, the effect of implant
      malalignment on wear-inducing loads is not yet known. This in vitro study
      determined the effect of anterior malpositioning and varus-valgus and internal
      external malrotations on humeral stem loading in total elbow arthroplasty.
      METHODS AND MATERIALS: Computer-navigated linked elbow arthroplasty was conducted
      in 8 cadaveric elbows. A modular, instrumented humeral component was used to
      measure loading during simulated elbow motion while the position of the ulna
      relative to the humerus was recorded. RESULTS: Loading increased for all
      malaligned implant positions tested (P < .05). During simulation of implant
      malpositioning, combinations of internal-external and varus-valgus malrotations
      that tended to preserve the line of action of the elbow flexors had lower loads
      than combinations that did not. DISCUSSION: This in vitro study showed that
      loading does increase after humeral component malalignment; however, further
      studies are required to determine the long-term effects on polyethylene wear and
      component loosening.

PMID- 21868257
TI  - New onset left frontal lobe seizure presenting with ictal asystole.
AB  - Ictal asystole is a presumably rare but potentially fatal complication of
      seizures, most often of temporal lobe origin. It is believed that at least some
      cases of sudden unexplained death in epilepsy (SUDEP) might be triggered by ictal
      bradycardia or asystole. Current standard practice is to implant a permanent
      pacemaker in these patients to prevent syncope and/or death. However, emerging
      data suggests that effective medical or surgical treatment of epilepsy might be
      enough to prevent cardiac asystole, eliminating the need for permanent pacemaker
      placement. We describe a case of new onset left frontal lobe epilepsy in a young
      athletic patient who presented with near-syncopal episodes but whose
      comprehensive work-up revealed frequent events of ictal bradycardia and asystole.
      He responded well to monotherapy using oxcarbazepine, avoiding a permanent
      pacemaker.

PMID- 21868258
TI  - SCN1A mutational analysis in Korean patients with Dravet syndrome.
AB  - OBJECTIVE: The aim of this study was to characterize the SCN1A mutation spectrum
      in Korean patients with Dravet syndrome. METHODS: Twenty-nine patients diagnosed
      with Dravet syndrome at the Seoul National University Children's Hospital were
      included in the study. Direct sequencing and multiplex ligation-dependent probe
      amplification (MLPA) were used to identify SCN1A mutations. Mutations were
      classified as either truncation (nonsense and frameshift) or missense mutations.
      RESULTS: Nineteen pathogenic mutations (19/29; 66%) and three unclassified
      variants were identified. One large deletion mutation spanning exons 1-20 was
      detected using MLPA. Fifteen of these 19 SCN1A mutations were novel. Eleven
      mutations were classified as truncations (seven frameshift and four nonsense
      mutations) and seven were classified as missense mutations. Truncating mutations
      spanned the whole span of subunits of the SCN1A protein, whereas all missense
      mutations were localized at either the voltage sensor (S4) or the ion pore (S5
      S6) regions. Analysis according to clinical phenotype revealed that SCN1A
      mutations were more frequent in the classic group than in the borderline group
      (78% vs. 45%). CONCLUSIONS: SCN1A mutational analysis of Korean Dravet syndrome
      patients resulted in the identification of 15 novel mutations, which could expand
      the spectrum of SCN1A mutations and confirms the current understanding of
      genotype-phenotype correlations.

PMID- 21868259
TI  - Epilepsy specialist nurse prescribing practice in the United Kingdom: a national
      questionnaire survey.
AB  - Recent advances in legislation have enabled nurses in the United Kingdom (UK) to
      become Nurse Independent and Supplementary Prescribers (NISP). The NISP can
      assess, diagnose and independently prescribe any licensed medicine within their
      area of competence. This change has meant the number of nurse prescribers in
      disease specific areas has increased. This study set out to assess the number of
      Epilepsy Specialist Nurses (ESNs) prescribing and the context in which they do
      so. A draft questionnaire was developed and piloted with 10 ESNs. Minor changes
      to improve data collection were made. In April 2009 all known ESNs were invited
      via letter to complete the questionnaire. One month later a follow up reminder
      was mailed to all ESNs to encourage participation. Data was analyzed using
      percentages and cross tabulation. Completed questionnaires were returned by 29
      nurse prescribers. Twenty ESNs were working as independent nurse prescribers, 6
      as supplementary nurse prescribers and 3 as both. Prescribing practice
      demonstrated that 21 (72%) signed prescriptions, 28 (97%) made recommendations to
      other prescribers, 14 (48%) prescribed or amended ward/in patient drug
      prescriptions and 10 (34%) used clinical management plans. The medications
      prescribed by ESNs included anti-epilepsy medication, folic acid, vitamin K, anti
      depressants, steroids, rescue medication and the contraceptive pill. Most ESNs
      wrote a prescription for a new drug at least once a week whilst most nurses
      titrated medication daily. Nurse prescribers held higher academic qualifications
      and had worked in the field of epilepsy for years. Epilepsy specialist nurse
      prescribing enabled a holistic approach to patient care. This paper identified
      the need for ESNs to update annually and audit their prescribing practice.

PMID- 21868260
TI  - Decreased ezrin and paxillin expression in human urothelial bladder tumors
      correlate with tumor progression.
AB  - OBJECTIVES: F-actin binding proteins ezrin and paxillin are involved in cell
      adhesion and cell migration/invasion. The aim of the study was to investigate
      their role in urothelial bladder carcinogenesis. MATERIALS AND METHODS:
      Expression of ezrin and paxillin was studied by immunohistochemistry in 104 and
      96 cases of urothelial bladder tumors, respectively. Correlations with
      clinicopathologic data and expression of p53, E-cadherin, and beta-catenin were
      examined. RESULTS: Positive ezrin and paxillin protein expression was found in
      99% and 93.7% of cases, respectively. Membranous expression of ezrin was
      significantly lower in high grade tumors and correlated with invasion.
      Multivariate analysis showed that ezrin is an independent predictor of muscularis
      propria invasion. Paxillin expression was significantly decreased in urothelial
      carcinomas compared with tumors of low malignant potential and low paxillin
      levels also correlated with advancing tumor stage and invasion. A statistically
      significant correlation was found between membranous ezrin and E-cadherin as well
      as between ezrin and paxillin expression in urothelial tumors. CONCLUSIONS: Down
      regulation of ezrin and paxillin in urothelial bladder tumors is associated with
      aggressive tumor features and invasiveness.

PMID- 21868261
TI  - Transition zone PSA density improves the prostate cancer detection rate both in
      PSA 4.0-10.0 and 10.1-20.0 ng/ml in Chinese men.
AB  - OBJECTIVES: We hypothesized the prostate-specific antigen (PSA) "grey zone" in
      Chinese men was higher than the traditional value (4.0-10.0 ng/ml) since
      incidence of prostate cancer (CaP) in Chinese men was relative low. We then
      assessed the efficiencies of transition zone PSA density (TZPSAD) in the
      diagnosis of CaP in Chinese men with a PSA of both 4.0-10.0 and 10.1-20.0 ng/ml.
      MATERIALS AND METHODS: Men had a prostatic biopsy for detecting CaP from November
      1999 to August 2009 were retrospectively retrieved from our computer center.
      Those had a document of transrectal ultrasound transition zone measurement with a
      PSA of 4.0-20.0 ng/ml were included. Receiver-operating characteristic (ROC)
      curve was used to analyze the efficiencies of PSA and TZPSAD in the diagnosis of
      CaP. RESULTS: A total of 189 men were included in the study. Of these men, 78 and
      111 had a PSA of 4.0-10.0 and 10.1-20.0 ng/ml, respectively. The rate of CaP in
      men with a PSA of 4.0-10.0 ng/ml was not statistically significantly different
      compared with those with a PSA of 10.1-20.0 ng/ml (20.5% vs. 21.6%, P = 0.854).
      The areas under the ROC curve (AUCs) in diagnosis of CaP for PSA and TZPSAD were
      0.569 and 0.702 in men with a PSA of 4.0-10.0 ng/ml and 0.463 and 0.730 in men
      with a PSA of 10.1-20.0 ng/ml, respectively. The best cut-off of TZPSAD in
      predicting CaP in men with a PSA of 4.0-10.0 ng/ml was 0.370 ng/ml/ml, the
      sensitivity of which equaled 68.8%, specificity 72.6%. The best cut-off of TZPSAD
      in predicting CaP in men with a PSA of 10.1-20.0 ng/ml was 0.500 ng/ml/ml. Its
      sensitivity equaled 70.8%, specificity 70.1%. CONCLUSIONS: Using TZPSAD can
      improve the efficiency of PSA in diagnosis of CaP and decreases the unnecessary
      prostatic biopsy in men with a PSA of both 4.0-10.0 and 10.1-20.0 ng/ml in
      Chinese men.

PMID- 21868262
TI  - Intravesical bacillus Calmette-Guerin immunotherapy after previous prostate
      radiotherapy for high-grade non-muscle-invasive bladder cancer.
AB  - OBJECTIVES: Intravesical bacillus Calmette-Guerin (BCG) immunotherapy is a
      standard treatment for high-grade non-muscle-invasive bladder cancer (NMIBC). We
      evaluated outcomes of BCG therapy for NMIBC in patients with a previous history
      of prostate cancer (CaP) radiotherapy (RT). MATERIALS AND METHODS: A
      retrospective review of patients with a history of CaP RT who subsequently
      underwent treatment with intravesical BCG for high-grade NMIBC was performed.
      Patients were categorized as "BCG success" or "BCG failure" (defined as stage
      progression or recurrent/persistent disease). We evaluated factors related to the
      radiotherapy (type, interval to BCG), bladder cancer (clinical stage,
      immunotherapy type, and course), and patient comorbidities, to identify factors
      associated with BCG failure. RESULTS: From 1996 to 2008, 26 patients with high
      grade NMIBC received intravesical BCG immunotherapy after CaP RT. At a mean
      follow-up of nearly 5 years, 13 patients (50%) were successfully managed with one
      or more induction courses of BCG with or without the addition of interferon
      alpha. Twelve (46%) eventually required cystectomy for disease recurrence or
      progression, of which half had pathologically advanced disease (>=pT3). Clinical
      stage was similar between BCG success and failure patients (P = 0.40). Those who
      failed immunotherapy were more likely to have had a longer interval between RT
      and BCG induction (5.8 vs. 2.4 years, P = 0.02). CONCLUSION: Approximately 50% of
      patients with NMIBC who were previously exposed to prostate radiation had a
      durable response to intravesical BCG. For non-responders, extravesical
      progression was common.

PMID- 21868264
TI  - Rationale of novel interventions for resistant hypertension.

PMID- 21868263
TI  - JAK3 in clear cell renal cell carcinoma: mutational screening and clinical
      implications.
AB  - OBJECTIVES: Janus Kinase 3 (JAK3) mediates cytokine signaling and T-cell
      activation. We hypothesized that JAK3 mutations may contribute to the development
      and progression of clear cell renal cell carcinoma (ccRCC). To test this
      hypothesis, we performed mutational screening and functional studies. PATIENTS
      AND METHODS: This hospital-based case-control study included 50 patients with
      ccRCC and 100 age- and gender-matched controls. Both genomic and tumor DNA were
      extracted. All 23 JAK3 exons were amplified by PCR and analyzed by denaturing
      high-performance liquid chromatography and automatic sequencing. Effects of JAK3
      mutations on interleukin-2-stimulated peripheral T-cells were analyzed by
      confocal laser-scanning microscopy and immunoprecipitation. RESULTS: Four
      different JAK3 germline missense mutations (p.Gln13Lys; p.Arg925Ser; p.Ala677Thr,
      p.Val722Ile) were found in a total of 7 ccRCC patients (14%), but in none of the
      controls (P = 0.0006). All germline mutations were similarly detected in the
      tumors. An additional somatic missense mutation (p.Tyr238Cys) was found in a
      patient who had a germline mutation. Four of the mutations have not been
      previously described (p.Gln13Lys; p.Arg925Ser; p.Ala677Thr, p.Tyr238Cys).
      Patients with JAK3 mutations more frequently presented with metastases (3 out of
      4 [75%] vs. 4 out of 46 [9%]; P = 0.004) and had poorer survival (P = 0.049). In
      p.Arg925Ser and p.Ala677Thr/p.Val722Ile, functional analyses showed abnormal JAK3
      and STAT5 tyrosine phosphorylation and a reduction of JAK3/STAT5 interaction.
      CONCLUSIONS: JAK3 mutations are found in a subset of ccRCC patients and may be
      associated with ccRCC development and a greater risk of metastases. JAK3 function
      is compromised in p.Arg925Ser and p.Ala677Thr/p.Val722Ile. Future studies with a
      larger number of patients need to confirm these findings.

PMID- 21868265
TI  - Pediatric Wegener's granulomatosis with oral ulcers and progressive
      periodontitis: a case report.
AB  - Wegener's granulomatosis (WG) is a rare multisystem disorder. Although it can
      occur at any age, it is rarely observed in children. Oral manifestations, which
      are present in fewer than 10% of patients, include oral ulceration, nonhealing
      extraction sockets, and the most common oral lesion, hyperplastic gingivitis,
      which is known as "strawberry gingivitis." We report the unusual case of a 6-year
      old boy with WG who presented with atypical oral manifestations, including severe
      progressive periodontitis accompanied by oral ulcers, before the development of
      systemic symptoms. Although WG is rare, this case emphasizes the importance of
      considering the diagnosis in those who present with progressive and atypical oral
      disease, as prompt treatment of the systemic illness can significantly improve
      outcome.

PMID- 21868266
TI  - Squamous cell carcinoma development in previously diagnosed oral lichen planus:
      de novo or transformation?
AB  - OBJECTIVES: The objectives of this study were to investigate the incidence of
      oral squamous cell carcinoma (OSCC) developing in lesions that were previously
      diagnosed as oral lichen planus (OLP), and to evaluate potential contributing
      factors that might be associated with an increased risk for the development of
      OSCC in these patients. STUDY DESIGN: We retrospectively reviewed a relatively
      large cohort of 518 patients with OLP who received long-term follow-up (range, 6
      months-21.5 years). RESULTS: There were 353 females and 165 males. Of these, 5
      (0.96%) patients developed OSCC with a mean duration of 70 months. All were
      females with no history of smoking or alcohol use. Four of them received
      corticosteroid therapy. Notably, 1 of these patients received systemic
      corticosteroid therapy 13 months before transformation, and died of metastatic
      disease 46 months after transformation. CONCLUSIONS: The incidence of OSCC
      developing in lesions previously diagnosed as OLP is less than 1%, and females
      were more commonly affected. These cases appear to represent the transformation
      of OLP into OSCC, however it cannot be entirely ruled out that these cases may
      represent de novo OSCC.

PMID- 21868269
TI  - Inflammatory myofibroblastic tumor of the maxillary sinus related with pulp
      necrosis of maxillary teeth: case report.
AB  - Inflammatory myofibroblastic tumor (IMT) is a benign lesion composed of
      myofibroblasts accompanied by varying numbers of inflammatory cells. Various
      pathogenetic factors have been proposed, but the etiology of most IMTs remains
      unknown. This article presents a case of IMT occurring in the left maxillary
      sinus. A 24-year-old man complained of throbbing pain in the maxillary left
      molars and swelling of the left cheek. His maxillary left second molar was
      diagnosed as pulp necrosis and root canal treatment performed. After that, his
      symptoms continued and he was referred to the Department of Otolaryngology.
      Computerized tomography disclosed compact soft tissue masses in the left
      maxillary sinus with obstruction of maxillary ostium. Under general anesthesia,
      the lesions were fully excised. Histopathologically, the lesions were composed of
      plump or spindled myofibroblasts. Cells were immunoreactive for smooth muscle
      actin and beta-catenin, and were negative for ALK1, CD34, and EMA. The diagnosis
      was IMT of left maxillary sinus. Although it is very rare, IMT should be included
      as a differential diagnosis in patients with compact masses in maxillary sinus.

PMID- 21868270
TI  - Developmental evolution in a patient with multiple acyl-coenzymeA dehydrogenase
      deficiency under pharmacological treatment.
AB  - PURPOSE: evaluate the psychomotor evolution of a child with Multiple acyl-CoA
      dehydrogenase deficiency after treatment with L-carnitine, ubiquinone and
      riboflavin. METHODS: an assessment of psychomotor development was performed
      before the start of farmacological treatment using the Assessment Scale of Mental
      Development Griffiths (GMDS-R, 0-2 years). The same assessment was performed
      after a month and after six months of treatment to evaluate the possible benefits
      of treatment. RESULTS: we noticed a quick and dramatic improvement in muscular
      tone and motor performances after pharmacological treatment. We also observed a
      substantial improvement in the personal/social and hearing/language areas,
      suggesting the presence of intellectual/cognitive improvement. The clinical
      improvement correlated with the biochemical response. CONCLUSION: In our patient
      early therapy resulted in a optimal response in psychomotor development, motor
      function and muscole hypotonia. Evaluation with GMDS-R, a simple, non-invasive
      and multidimensional tool, represents a useful instrument to monitor the clinical
      response to treatment.

PMID- 21868273
TI  - Effects of fasting and/or postprandial glucose on heart rate recovery in patients
      with coronary heart disease.
AB  - AIM: The impact of both fasting and postprandial glycaemia on heart rate recovery
      (HRR) has not been studied in patients with coronary heart disease (CHD). For
      this reason, we sought to determine the relationships between HRR and both
      fasting and postprandial glycaemia. METHODS: A total of 4079 patients with
      baseline fasting plasma glucose (FPG) levels and 706 patients with 2-hour
      postprandial glucose (2hPG) levels were identified from the Coronary Artery
      Surgery Study registry, a database of 24,958 patients with suspected or proven
      CHD who had undergone cardiac catheterization between 1974 and 1979. Median long
      term follow-up was 14.7 years (interquartile range: 9.8-16.2 years). The
      relationships between HRR and both FPG and 2hPG were studied. RESULTS: In
      univariate analyses, increasing levels of both FPG and 2hPG were significantly
      associated with lower HRR. In multivariate models adjusted for age, exercise
      tolerance in METs, resting heart rate and maximum systolic blood pressure during
      exercise testing, FPG remained significantly associated with HRR while 2hPG did
      not. CONCLUSION: Both raised FPG and decreased HRR are independent predictors of
      total and cardiovascular (CV) mortality in subjects with CHD. Our data suggest
      that the mortality risk associated with elevated FPG may in part be due to
      deleterious effects on autonomic regulation of CV function, as reflected by lower
      HRR. Further studies are required to determine whether or not non-pharmacological
      and/or pharmacological treatments of increased fasting glucose have a beneficial
      influence on HRR.

PMID- 21868272
TI  - Membrane fluidity profiles as deduced by saturation-recovery EPR measurements of
      spin-lattice relaxation times of spin labels.
AB  - There are no easily obtainable EPR spectral parameters for lipid spin labels that
      describe profiles of membrane fluidity. The order parameter, which is most often
      used as a measure of membrane fluidity, describes the amplitude of wobbling
      motion of alkyl chains relative to the membrane normal and does not contain
      explicitly time or velocity. Thus, this parameter can be considered as
      nondynamic. The spin-lattice relaxation rate (T(1)(-1)) obtained from saturation
      recovery EPR measurements of lipid spin labels in deoxygenated samples depends
      primarily on the rotational correlation time of the nitroxide moiety within the
      lipid bilayer. Thus, T(1)(-1) can be used as a convenient quantitative measure of
      membrane fluidity that reflects local membrane dynamics. T(1)(-1) profiles
      obtained for 1-palmitoyl-2-(n-doxylstearoyl)phosphatidylcholine (n-PC) spin
      labels in dimyristoylphosphatidylcholine (DMPC) membranes with and without 50
      mol% cholesterol are presented in parallel with profiles of the rotational
      diffusion coefficient, R(?), obtained from simulation of EPR spectra using
      Freed's model. These profiles are compared with profiles of the order parameter
      obtained directly from EPR spectra and with profiles of the order parameter
      obtained from simulation of EPR spectra. It is shown that T(1)(-1) and R(?)
      profiles reveal changes in membrane fluidity that depend on the motional
      properties of the lipid alkyl chain. We find that cholesterol has a rigidifying
      effect only to the depth occupied by the rigid steroid ring structure and a
      fluidizing effect at deeper locations. These effects cannot be differentiated by
      profiles of the order parameter. All profiles in this study were obtained at X
      band (9.5 GHz).

PMID- 21868274
TI  - Ultrasound promoted reaction of Rhodamine B with sodium hypochlorite using
      sonochemical and dental ultrasonic instruments.
AB  - The sonochemical acceleration of bleaching of Rhodamine B by sodium hypochlorite
      has been studied using ultrasound intensities in the range 0-7 W cm(-2). Using a
      20 kHz ultrasonic horn, it was shown that ultrasound could significantly shorten
      the treatment time and/or the concentration of hypochlorite required for the
      reaction. A number of intermediate species formed during the reaction have been
      identified. It was demonstrated that the same sonochemical reactions occur during
      the use of dental ultrasound instruments of the type used in endodontics where
      hypochlorite solutions act as disinfectants. Results showed pseudo-first order
      degradation kinetics for the degradation of Rhodamine B for both types of source.
      Both the distribution of cavitation and the resulting bleaching reactions were
      dependent on the design of the tips. The bleaching reaction can therefore be used
      to characterise the behaviour of dental instruments and aid in the optimisation
      of their performance.

PMID- 21868275
TI  - Ultrasound-promoted catalyst-free one-pot four component synthesis of 2H
      indazolo[2,1-b]phthalazine-triones in neutral ionic liquid 1-butyl-3
      methylimidazolium bromide.
AB  - A catalyst-free one-pot four component methodology for the synthesis of 2H
      indazolo[2,1-b]phthalazine-triones under ultrasonic irradiation at room
      temperature using 1-butyl-3-methylimidazolium bromide, [Bmim]Br, as a neutral
      reaction medium is described. A broad range of structurally diverse aldehydes
      (aromatic aldehydes bearing electron withdrawing and/or electron releasing groups
      as well as heteroaromatic aldehydes) were applied successfully, and corresponding
      products were obtained in good to excellent yields without any byproduct.

PMID- 21868276
TI  - White matter hyperintensities in patients with multiple system atrophy.
AB  - INTRODUCTION: Although white matter hyperintensities (WMHs) are prevalent in the
      elderly, the clinical significance and the underlying pathophysiological
      mechanisms of WMHs in neurodegenerative disorders have not been fully clarified.
      OBJECTIVE: The present study aimed to determine the degree of WMHs in patients
      with multiple system atrophy (MSA), and analyze the predisposing factors for
      WMHs. METHODS: Two raters blinded to clinical information assessed
      cerebrovascular lesions in brain MRIs from patients with MSA and age-matched
      controls. Patients with Parkinson's disease (PD) were similarly studied as a
      disease control. The results obtained were compared with the clinical
      characteristics of the patients and statistically analyzed. RESULTS: WMHs in
      patients with MSA were statistically greater compared with PD patients or
      controls. There were no significant differences in either lacunar or territorial
      infarcts. Multiple linear regression analysis demonstrated that age, supine
      systolic blood pressure, and a drop in orthostatic blood pressure were
      significantly and independently correlated with WMH scores in MSA. CONCLUSIONS:
      The present study suggests that white matter is differentially involved in MSA.
      In addition to aging, cerebral hypoperfusions caused by fluctuations of blood
      pressure may be a significant contributing factor to WMHs in MSA, although the
      possibility that degenerative processes occurring in oligodendrocytes may be
      associated with WMHs should not be excluded.

PMID- 21868277
TI  - Parkinsonian features in a patient with diffuse neurofibrillary tangles with
      calcification (DNTC).

PMID- 21868278
TI  - Advanced Theory of Mind in patients at early stage of Parkinson's disease.
AB  - Advanced Theory of Mind (ToM) refers to the sophisticated ability to infer other
      people's thoughts, intentions, or emotions in social situations. With appropriate
      advanced ToM, one can behave well in social interactions and can understand the
      intention of others' behavior. Prefrontal cortex plays a vital role in this
      ability, as shown in functional brain imaging and lesion studies. Considering the
      primary neuropathology of Parkinson's disease (PD) involving the frontal lobe
      system, patients with PD are expected to exhibit deficits in advanced ToM.
      However, few studies on this issue have been explored, and whether advanced ToM
      is independent of executive functions remains uncertain. Thirty-nine early non
      demented PD patients and 40 normal control subjects were included. Both groups
      were matched in age, level of education, and verbal intelligence quotient. Each
      participant received advanced ToM, executive functions, and verbal intelligence
      quotient tests. We discovered that the performance of the PD patients on the
      Cartoon ToM task was significantly poorer than that of their normal counterparts.
      Correlation analysis revealed that performance scores of advanced ToM in PD
      patients were significantly associated with their executive functions scores;
      however, this is not the case for normal controls. We conclude that dysfunction
      of advanced ToM develops in early PD patients, who require more cognitive
      abilities than their normal counterparts to generate advanced ToM. Our findings
      might be helpful in developing educational and medical care programs for PD
      patients in the future.

PMID- 21868279
TI  - An international analysis of contact lens compliance.
AB  - PURPOSE: To evaluate compliance to contact lens use in 14 countries, and to
      identify wearer attributes which indicate lower compliance levels. METHODS: A web
      based survey was undertaken by 4021 contact lens wearers, revealing information
      about demographics, and lens and solution information including daily handling
      details, case care and aftercare frequency. Particular attention was paid to
      eight modifiable compliance-related behaviours which are associated with an
      increased risk of microbial keratitis. RESULTS: Full compliance was very rare for
      most lens users, although better (15% of wearers) for daily disposable lenses.
      Reduced compliance was demonstrated in South Korea, and for young male full-time
      contact lens users, especially those who have not consulted their eyecare
      practitioner for some time. The behaviours associated with the lowest levels of
      compliance were rubbing and rinsing, handwashing, correct lens replacement and
      case cleaning. CONCLUSIONS: Given other recent literature, which suggests
      improved contact lens compliance with regular self-review exercises, we encourage
      clinical colleagues to particularly examine case cleaning, handwashing and
      rubbing and rinsing at aftercare examinations, especially in young male wearers.

PMID- 21868280
TI  - Salivary endothelin-1 potential for detecting oral cancer in patients with oral
      lichen planus or oral cancer in remission.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor involved not only in vascular
      biology but also in carcinogenesis. Results of a study in 2007 suggested salivary
      ET-1 as a potential biomarker for oral squamous cell carcinoma (OSCC), but a
      later study showed conflicting results. The purpose of our pilot study was to
      investigate feasibility of using salivary ET-1 as a biomarker for OSCC in two
      groups: oral lichen planus (OLP) patients and patients with OSCC in remission.
      Saliva samples were collected from five groups of subjects: patients with newly
      diagnosed, active OSCC (Group A); patients with OSCC in remission (Group B);
      patients with active OLP lesions (Group C); patients with OLP in remission (Group
      D); and normal controls (Group E). Salivary ET-1 levels were determined by enzyme
      linked immunosorbent assay, and the results were analyzed by the Mann-Whitney U
      test. The mean salivary ET-1 level in Group A was significantly higher than that
      found in Group C (p=0.001), Group D (p=0.015) or Group E (p=0.004). There were no
      significant differences (p>0.05) in the mean salivary ET-1 levels between Groups
      A and B; Groups B and C; Groups B and D; Groups B and E; Groups C and D; Groups C
      and E; or Groups D and E. Salivary ET-1 could be a good biomarker for OSCC
      development in OLP patients regardless of the degree of OLP disease activity.
      However, it appeared not to be a good biomarker for detecting recurrence of OSCC
      in patients in remission.

PMID- 21868281
TI  - The next generation of bacteriophage therapy.
AB  - Bacteriophage therapy for bacterial infections is a concept with an extensive but
      controversial history. There has been a recent resurgence of interest into
      bacteriophages owing to the increasing incidence of antibiotic resistance and
      virulent bacterial pathogens. Despite these efforts, bacteriophage therapy
      remains an underutilized option in Western medicine due to challenges such as
      regulation, limited host range, bacterial resistance to phages, manufacturing,
      side effects of bacterial lysis, and delivery. Recent advances in biotechnology,
      bacterial diagnostics, macromolecule delivery, and synthetic biology may help to
      overcome these technical hurdles. These research efforts must be coupled with
      practical and rigorous approaches at academic, commercial, and regulatory levels
      in order to successfully advance bacteriophage therapy into clinical settings.

PMID- 21868282
TI  - Keratoconjunctivitis sicca of human T cell lymphotropic virus type 1 (HTLV-1)
      infected individuals is associated with high levels of HTLV-1 proviral load.
AB  - BACKGROUND: A high HTLV-1 proviral load is found in HTLV-1-associated diseases,
      mainly HAM/TSP. However, the association between proviral load and
      keratoconjunctivitis sicca (KCS) has not been well established. AIM: To verify
      the association between KCS and HTLV-1 proviral load. STUDY DESIGN: 104 HTLV-1
      infected patients (51 asymptomatic and 52 with HAM/TSP) from the HTLV reference
      center in Salvador, Brazil were followed from June 2008 to May 2010. Evaluation
      of tear secretion was performed by BUT (break-up time), Rose Bengal and Schirmer
      I tests. The diagnosis of KCS was based upon the presence of symptoms and when at
      least two of three tests were positive. HTLV-1 proviral load was determined using
      real-time PCR. RESULTS: The prevalence of KCS was 44.2%. KCS was more frequent
      among HAM/TSP patients (p = 0.022). Patients with KCS had higher proviral load
      (mean 134,672 +/- 150,393copies/10(6) PBMC) than patients without the disease
      (mean 66,880 +/- 109,525copies/10(6) PBMC) (p = 0.001). HTLV-1 proviral
      load>100,000copies/10(6) PBMC increased significantly the risk of developing KCS
      (OR = 4.05 and 95% CI = 1.40-11.76). After age>45 years and HAM/TSP status were
      excluded in stepway reward analysis, the variables PVL>100,000 (OR = 4.77 and 95%
      CI = 1.83-12.44) still remained statistically significant. CONCLUSION: HTLV-1
      proviral loads are higher in patients with KCS and may represent a relevant
      biological marker of disease.

PMID- 21868283
TI  - Intraoperative MRI in glioma surgery: proof of benefit?

PMID- 21868284
TI  - Intraoperative MRI guidance and extent of resection in glioma surgery: a
      randomised, controlled trial.
AB  - BACKGROUND: Intraoperative MRI is increasingly used in neurosurgery, although
      there is little evidence for its use. We aimed to assess efficacy of
      intraoperative MRI guidance on extent of resection in patients with glioma.
      METHODS: In our prospective, randomised, parallel-group trial, we enrolled adults
      (>=18 years) with contrast enhancing gliomas amenable to radiologically complete
      resection who presented to Goethe University (Frankfurt, Germany). We randomly
      assigned patients (1:1) with computer-generated blocks of four and a sealed
      envelope design to undergo intraoperative MRI-guided surgery or conventional
      microsurgery (control group). Surgeons and patients were unmasked to treatment
      group allocation, but an independent neuroradiologist was masked during analysis
      of all preoperative and postoperative imaging data. The primary endpoint was rate
      of complete resections as established by early postoperative high-field MRI (1.5
      T or 3.0 T). Analysis was done per protocol. This study is registered with
      ClinicalTrials.gov, number NCT01394692. FINDINGS: We enrolled 58 patients between
      Oct 1, 2007, and July 1, 2010. 24 (83%) of 29 patients randomly allocated to the
      intraoperative MRI group and 25 (86%) of 29 controls were eligible for analysis
      (four patients in each group had metastasis and one patient in the intraoperative
      MRI group withdrew consent after randomisation). More patients in the
      intraoperative MRI group had complete tumour resection (23 [96%] of 24 patients)
      than did in the control group (17 [68%] of 25, p=0.023). Postoperative rates of
      new neurological deficits did not differ between patients in the intraoperative
      MRI group (three [13%] of 24) and controls (two [8%] of 25, p=1.0). No patient
      for whom use of intraoperative MRI led to continued resection of residual tumour
      had neurological deterioration. One patient in the control group died before 6
      months. INTERPRETATION: Our study provides evidence for the use of intraoperative
      MRI guidance in glioma surgery: such imaging helps surgeons provide the optimum
      extent of resection. FUNDING: None.

PMID- 21868285
TI  - The tubal hypothesis of ovarian cancer: caution needed.

PMID- 21868286
TI  - Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic
      review.
AB  - We did a systematic review to address the added value of intraoperative MRI
      (iMRI)-guided resection of glioblastoma multiforme compared with conventional
      neuronavigation-guided resection, with respect to extent of tumour resection
      (EOTR), quality of life, and survival. 12 non-randomised cohort studies matched
      all selection criteria and were used for qualitative synthesis. Most of the
      studies included descriptive statistics of patient populations of mixed
      pathology, and iMRI systems of varying field strengths between 0.15 and 1.5
      Tesla. Most studies provided information on EOTR, but did not always mention how
      iMRI affected the surgical strategy. Only a few studies included information on
      quality of life or survival for subpopulations with glioblastoma multiforme or
      high-grade glioma. Several limitations and sources of bias were apparent, which
      affected the conclusions drawn and might have led to overestimation of the added
      value of iMRI-guided surgery for resection of glioblastoma multiforme. Based on
      the available literature, there is, at best, level 2 evidence that iMRI-guided
      surgery is more effective than conventional neuronavigation-guided surgery in
      increasing EOTR, enhancing quality of life, or prolonging survival after
      resection of glioblastoma multiforme.

PMID- 21868287
TI  - Optimizing dosage to prevent emergence of resistance - lessons from in vitro
      models.
AB  - The widespread emergence of resistance to antimicrobial agents has taken mammoth
      dimension and warrants immediate steps to minimize it.
      Pharmacokinetics/pharmacodynamics of antimicrobial agents, differences among
      bacterial species, and time-dependent changes in the bacterial population are
      important factors involved in the development of drug resistance. The key to
      minimizing resistance lies in understanding how these factors affect resistance
      emergence and incorporating them in dosing regimen design. In vitro models have
      proven to be a valuable tool to study these factors and their contribution in
      resistance emergence. This review summarizes the key factors implicated in
      resistance development and the lessons learnt from in vitro studies optimizing
      antimicrobial dosing to prevent resistance emergence.

PMID- 21868288
TI  - Provocative lumbar discography versus functional anesthetic discography: a
      comparison of the results of two different diagnostic techniques in 52 patients
      with chronic low back pain.
AB  - BACKGROUND CONTEXT: There is mounting evidence that the currently available
      techniques for the diagnosis of discogenic low back pain are insufficiently
      accurate-this may explain some of the variability in outcomes of surgery for this
      important clinical problem. New diagnostic methods are needed to address this
      diagnostic issue; improvements here may do as much to improve overall patient
      outcomes as improvements in surgical treatment methods. PURPOSE: To compare the
      results of standard pressure-controlled provocative discography (PD) to those of
      the functional anesthetic discogram (FAD) in a series of patients presenting with
      chronic low back pain and considering surgical treatment. STUDY DESIGN:
      Prospective clinical series in an academic spinal surgical practice. PATIENT
      SAMPLE: Fifty-two patients presenting with chronic low back pain; mean age 45
      years (range, 24-70 years); 28 women, 24 men; and 25% in workman's compensation
      program. OUTCOME MEASURES: Oswestry, visual analog scale for back pain, distress
      and risk assessment method psychometric analysis, demographic data, magnetic
      resonance imaging scan of lumbar spine. During provocative discogram:
      pressurization at pain, pain level, and concordancy. During FAD: position or
      activity used to elicit typical pain, baseline pain level before injection,
      during injection, at 5, 10, and 20 minutes after the injection, and substance
      injected. METHODS: Standard pressure-controlled PD was performed, followed by (in
      positive cases or in patients with clinical features and imaging studies felt to
      be highly suggestive of symptomatic disc degeneration) the FAD test-an assessment
      of the response to injection of a low dose of local anesthetic into the disc
      during a position productive of the patient's typical pain. RESULTS: Discordant
      results of the two tests were noted in 46% of the patients in the series. Of
      them, 26% of patients with positive PD had negative findings on the FAD test; 16%
      had positive findings at a single level only, whereas the provocative discogram
      had been positive at two or more levels; 4% had new positive findings on the FAD
      test. CONCLUSIONS: We have presented the results of a new diagnostic technique in
      52 patients with chronic low back pain presumed discogenic in origin that was
      designed to help differentiate between symptomatic and asymptomatic disc
      degeneration. The findings of the test differed from those of standard pressure
      controlled PD in 46% of the cases reported on here. Further studies are needed to
      demonstrate the clinical utility of the test.

PMID- 21868289
TI  - Timing of postseed imaging influences rectal dose-volume parameters for cesium
      131 prostate seed implants.
AB  - PURPOSE: To study the influence of timing of postseed implant imaging on rectal
      dose-volume parameters for cesium-131 ((131)Cs) seed prostate implants. METHODS
      AND MATERIALS: Fifteen patients were treated in our institution with combination
      (131)Cs brachytherapy followed by pelvic external beam radiation therapy for
      intermediate to high-risk prostate cancers. For all patients, CT scans were
      scheduled at 7 days (CT(7)) and again at 2 months for external beam radiation
      therapy simulation purpose (CT(60)) postseed implantation. Comprehensive postseed
      implant dosimetry was performed for both CT(7) and CT(60) scans. In each case,
      dose-volume histogram parameters, rectal separation (the distance between the
      center of posterior most seed and most anterior rectal wall), and posterior row
      activity (the total activity implanted within 2-4mm anterior to the posterior
      wall of the prostate) data were collected. The absolute rectal volumes receiving
      100% and 110% prescription dose were also collected. RESULTS: Rectal dose
      correlated strongly with rectal separation (p<0.001). The mean change in rectal
      separation between CT(7) and CT(60) scans was 1.1 (+/-1.7) mm, and the
      corresponding change in 0.1-cc rectal dose was 18 (+/-26.5) Gy. Posterior row
      activity did not correlate with rectal dose (p=0.51). The mean volume of rectum
      that receives between 100% and 110% of the prescription dose (RV(100) and
      RV(110)) increased twofold, between CT(7) and CT(60) evaluations (0.03 [+/-0.06]
      cc vs. 0.07 (+/-0.05) cc, respectively, p=0.06). CONCLUSIONS: Our study has
      demonstrated that rectal doses after (131)Cs seed implants are influenced by the
      timing of postseed imaging. This may be a consequence of prostatic and
      periprostatic edema resolution.

PMID- 21868290
TI  - Cardiovascular autonomic dysfunction in sickle cell anemia.
AB  - Sickle cell anemia (SCA) is associated to increased cardiac output, normal heart
      rate (HR), abnormal QT dispersion and lower diastolic blood pressure (DBP). The
      mechanisms are still unknown. The objective of this study was to test the
      hypothesis that there is cardiovascular autonomic dysfunction (CAD) in SCA. The
      secondary objectives were to distinguish the roles of chronic anemia and
      hemoglobinopathy and to evaluate the predominance of the sympathetic or
      parasympathetic systems in the pathogenesis of CAD. Sixteen subjects with SCA, 13
      with sickle cell trait (SCT), 13 with iron deficiency anemia (IDA), and 13
      healthy volunteers (HV) were evaluated. All subjects were submitted to 24h
      electrocardiogram (24h-ECG), plasma norepinephrine (NE) measurement before and
      after isometric exercise (IE), and also Valsalva maneuver (VM), diving maneuver
      (DV), and tilt test (TT). Baroreflex sensitivity (BRS) was also evaluated. The
      minimum, average and maximum HR as well as the percentage of bradycardia and
      tachycardia at 24-h ECG were similar in all groups. NE at baseline and after IE
      did not differ between groups. The SCA group showed less bradycardia at phase IV
      of VM, less bradycardia during DV, and also less tachycardia and lower DBP during
      TT. BRS for bradycardia and tachycardia reflex was decreased in the SCA and SCT
      groups. In conclusion, 1) there is CAD in SCA, and it is characterized by the
      reduction of BRS and the limitation of HR modulation mediated by the
      parasympathetic system; 2) cardiovascular sympathetic activity is preserved in
      SCA; and 3) hemoglobinopathy is the preponderant ethiopathogenic factor.

PMID- 21868291
TI  - 53BP1-mediated DNA double strand break repair: insert bad pun here.
AB  - 53BP1 is an established player in the cellular response to DNA damage and is a
      canonical component of ionizing-radiation induced foci--that cadre of proteins
      which assemble at DNA double strand breaks following radiation exposure and which
      are readily visualized by immunofluorescence microscopy. While its roles in p53
      regulation and cell cycle checkpoint activation have been studied for some time,
      the impact of 53BP1 on DNA double strand break rejoining has only come to light
      in the past few years. Convincing evidence now exists for 53BP1 significantly
      affecting the outcome of DNA double strand break repair in several contexts, many
      of which hint to an important role in modulating chromatin structure surrounding
      the break site. Here, we highlight the known and emerging roles of 53BP1 in DNA
      double strand break repair, including the repair of lesions induced within
      heterochromatin, following telomere uncapping, in long-range V(D)J recombination,
      during immunoglobulin class switch recombination and its much debated role in
      regulating resection during homologous recombination.

PMID- 21868292
TI  - Validation of a UHPLC-FLD analytical method for the simultaneous quantification
      of aflatoxin B1 and ochratoxin a in rat plasma, liver and kidney.
AB  - A rapid and simple method for the simultaneous quantification of AFB1 and OTA in
      rat plasma, liver and kidney by UHPLC-FLD has been successfully validated
      according to the following criteria: selectivity, stability, linearity,
      precision, accuracy, recovery, robustness and limits of quantification and
      detection. The extraction method, calibration curves and chromatographic
      conditions are common for the three matrices. Plasma and homogenized tissue
      samples (100 MUL) were extracted with acetonitrile:formic acid mixture (99:1)
      (300 MUL). Chromatographic separation was performed with a mixture of water and
      acetonitrile:methanol (50:50), both acidified with 0.5% of formic acid using a
      gradient profile. The method avoids the use of immunoaffinity columns and allows
      reduction of sample and solvent volumes as well as toxic wastes. The detection is
      based on a photochemical reaction which enhances the AFB1 response without
      affecting the OTA signal before reaching the fluorescent detector. The mycotoxin
      recovery for each matrix was very efficient, between 93% and 96% for AFB1 and
      between 94% and 96% for OTA. For both mycotoxins the LOQs were 2MUg/L in plasma
      and 8MUg/kg in liver and kidney. The method has successfully been applied to rat
      samples after a single oral administration of a mixture of AFB1 and OTA and it
      could be a useful tool in toxicokinetic and toxicological studies.

PMID- 21868293
TI  - Quantitation of quinapril in human plasma by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry with quinolone matrix additives.
AB  - The renin-angiotensin-aldosterone system (RAAS) is an essential body fluid
      maintenance system that controls pressure in the human body. The conversion of
      angiotensin I to angiotensin II by angiotensin-converting enzyme (ACE) is a key
      process in the RAAS because angiotensin II causes the vasoconstriction
      association with hypertension. Because of its effectiveness as an ACE blocker,
      quinipril is widely used for clinical treatment of hypertension and chronic
      congestive heart failure(.) Matrix-assisted laser desorption/ionization coupled
      with time-of-flight analyzer (MALDI-TOF) is a high throughput instrument for
      biological sample analysis. This study developed a micro-scale approach for using
      MALDI-TOF to detect quinapril in biological samples. A micro-liquid-liquid
      extraction strategy combined with ion-pair interaction successfully extracted
      quinapril from aqueous layer to organic layer. Quinolones were then used as
      matrix additives to suppress undesired substances in plasma produce signals.
      Several factors affecting extraction efficiency were investigated in a biosample
      with a volume of only 10 MUL. This method is successful to monitor quinapril in
      the clinical therapeutic range. The proposed method proved effective for
      monitoring the trace amounts of quinapril typically used for clinical therapy.
      The relative standard deviation (R.S.D.) and relative error (R.E.) used for
      evaluating within- and between-day assays of quinapril in plasma consistently
      remained below 15%.

PMID- 21868294
TI  - Split anterolateral thigh (ALT) free flap for vulva reconstruction: a case
      report.
AB  - The anterolateral thigh (ALT) flap is a popular reconstructive choice due to its
      versatility and minimal donor site morbidity. It has been used in the
      reconstruction of perineal and vulval defects as a pedicled or free flap. We
      describe, for the first time, use of a split ALT flap to reconstruct a vulval
      defect following excision for recurrent tumour. Splitting the ALT increases the
      versatility yet further without compromising flap vascularity.

PMID- 21868295
TI  - Concepts in aesthetic breast dimensions: analysis of the ideal breast.
AB  - BACKGROUND: This article identifies the key parameters that define the aesthetic
      ideal of the breast. Whilst much has previously been written on the aesthetic
      characteristics of the breast, thus far objective indices of beauty have not been
      identified. METHODS: In this observational study the breasts of 100 consecutive
      women in three quarter profile pose, having been chosen as topless models for the
      attractiveness of their breasts by editors of mass print media, were analysed to
      identify specific proportions common to all of them. Analysis of a series of less
      attractive breasts was subsequently carried out looking at divergence from the
      'norms' identified in the first part of the study. RESULTS: We have identified 4
      key features consistently found in all the models in the consecutive series: the
      proportion of the upper to the lower pole is a 45:55 ratio, the angulation of the
      nipple is upwards at a mean angle of 20 degrees  from the nipple meridian, the
      upper pole slope is linear or slightly concave, and the lower pole is convex.
      CONCLUSIONS: Deviation from this pattern yields a less attractive breast - the
      greater the deviation, the less attractive the breast. The importance of this
      template lies in its use as a guide for the design of aesthetic breast surgery as
      well as objective analysis of both good and bad results.

PMID- 21868296
TI  - Evidence-based recommendations for negative pressure wound therapy: treatment
      variables (pressure levels, wound filler and contact layer)--steps towards an
      international consensus.
AB  - Negative pressure wound therapy (NPWT) is becoming a commonplace treatment in
      many clinical settings. New devices and dressings are being introduced. Despite
      widespread adoption, there remains uncertainty regarding several aspects of NPWT
      use. To respond to these gaps, a global expert panel was convened to develop
      evidence-based recommendations describing the use of NPWT. In a previous
      communication, we have reviewed the evidence base for the use of NPWT within
      trauma and reconstructive surgery. In this communication, we present results of
      the assessment of evidence relating to the different NPWT treatment variables:
      different wound fillers (principally foam and gauze); when to use a wound contact
      layer; different pressure settings; and the impact of NPWT on bacterial
      bioburden. Evidence-based recommendations were obtained by a systematic review of
      the literature, grading of evidence and drafting of the recommendations by a
      global expert panel. Evidence and recommendations were graded according to the
      Scottish Intercollegiate Guidelines Network (SIGN) classification system. In
      general, there is relatively weak evidence on which to base recommendations for
      any one NPWT treatment variable over another. Overall, 14 recommendations were
      developed: five for the choice of wound filler and wound contact layer, four for
      choice of pressure setting and five for use of NPWT in infected wounds. With
      respect to bioburden, evidence suggests that reduction of bacteria in wounds is
      not a major mode of action of NPWT.

PMID- 21868297
TI  - Application of low-pressure negative pressure wound therapy to ischaemic wounds.
AB  - Negative pressure wound therapy (NPWT) is a useful wound dressing that can be
      applied to a wide variety of wounds. Patients with ischaemic wounds, however, may
      experience further necrosis with NPWT at the commonly recommended pressure of 
      125 mm Hg. We hypothesized that with a suction pressure of -125 mm Hg, tissue
      pressure will likely occlude most of the capillaries adjacent to the wound edge.
      Therefore, we treated three patients with ischaemic wounds using low-pressure
      NPWT at -50 mm Hg. All wounds healed successfully without further necrosis at the
      wound edge.

PMID- 21868298
TI  - Variation with age of dental cephalometric variables in Class II, division 2
      patients.
AB  - The treatment of Angle Class II/2 malocclusion requires an understanding not only
      of the dental and maxillofacial features but also of the changes occurring with
      age in the dental relationships. This paper attempts to determine certain dental
      relationships in patients with Angle II/2 malocclusion and any changes that might
      occur with age. The study material included 96 lateral cephalometric X-rays of
      patients with Angle II/2 malocclusion, the youngest of whom was 7 years old and
      the eldest 35. Six cephalometric measurements were performed on every
      cephalometric X-ray. Statistical processing of data included one-variable
      analyses and correlations of two variables. Statistical one-variable analysis
      used methods from descriptive statistics. Methods of inferential statistics have
      been applied in order to revel statistical significance. The evaluation of the
      findings of this research study concluded that, in patients with Angle II/2
      malocclusion, maxillary central incisors presented pronounced palatal tipping,
      which exacerbated significantly with age, while mandibular incisors displayed
      reduced labial tipping and projection, which significantly reduced with age.
      Furthermore, it was found that there was pronounced incisor overjet, which
      increased with age, due to increased protrusion of mandibular incisors.

PMID- 21868300
TI  - Analysis of a claimed distant relationship in a deficient pedigree using high
      density SNP data.
AB  - DNA markers are routinely used to reveal both simple and complex family
      relationships. Likelihood based approaches have been traditionally used to
      estimate relationships using relatively few unlinked markers. However it is
      widely recognized that when using such limited numbers of loci distant
      relationships between two individuals cannot be distinguished from the average
      level of allele sharing found in random pairwise comparisons in the same
      population. As a real example, we demonstrate the usefulness of genome-wide SNP
      genotyping to analyze a claimed second cousin relationship that could not be
      resolved using standard forensic markers, confirming theoretical expectations for
      very distant relationships. Genome profiles derived from Affymetrix 6.0 SNP
      arrays obtained from the claimed second cousins were compared to profiles
      obtained from unrelated individuals and simulated data. Significance of the high
      estimated probabilities in favor of the second cousin relationship hypothesis was
      proved from the results obtained with both real and simulated unrelated pairs. As
      a final cautionary note, it is important to consider that successful
      identification of the claimed distant relationship reported here is largely due
      to a well-founded hypothesis being compared to the alternative hypothesis of the
      claimants being unrelated, but where there are several possible alternative
      hypotheses, the approach we outline here can yield false indications of unfounded
      alternative relationships.

PMID- 21868301
TI  - Efficiency of flexible derotator in walking cerebral palsy children.
AB  - INTRODUCTION: The flexible derotator is one of the therapeutic resources used to
      combat primary and secondary abnormalities in walking cerebral palsy children. It
      was developed to reduce abnormal femoral and tibial torsions and lessen the
      latter's negative functional impact. OBJECTIVE: To determine the effect of
      wearing a flexible derotator on anatomic and functional parameters in walking
      cerebral palsy children. METHODS: We performed a retrospective study of walking
      cerebral palsy children by gathering data on bone-related parameters (femoral and
      tibial torsion) and functional parameters (distance and speed gait, and the
      energy expenditure index (EEI)). Fifteen walking cerebral palsy children were
      treated with the flexible derotator for one year and 15 untreated walking
      cerebral palsy children were included as controls. The two groups were compared
      in terms of the various parameters' change over time between the initial
      examination (the last examination prior to the start of the study or prior to use
      of the flexible derotator) and the final examination (after one year of follow
      up). RESULTS: Right femoral anteversion and right and left external tibial
      torsion improved. There was a significant increase in distance and speed gait and
      a decrease in the EEI in walking cerebral palsy children. CONCLUSION: Our
      retrospective study revealed a significant improvement in functional parameters
      in children with cerebral palsy, as a result of wearing the flexible derotator
      for at least 6 hours a day for a year. Bone parameters only improved slightly.
      Use of the flexible derotator could improve these children's quality of life.

PMID- 21868302
TI  - Successful topical application of Ankaferd blood stopper in a patient with life
      threatening fundal variceal bleeding despite cyanoacrilate injection.
AB  - Gastric variceal bleeding is a common problem in patients with cirrhosis and
      despite early endoscopic and/or pharmacological therapy, variceal bleeding cannot
      be controlled or recurs early in about 10 to 20% of patients with considerable
      morbidity and mortality rates. For this reason, effective control of active
      bleeding varices is of great importance for the prevention of late complications.
      Although endoscopic band ligation and sclerotherapy are the choice of endoscopic
      treatment modalities with various grades of success, limited data is available
      for the use of Ankaferd Blood Stopper (ABS) for the controlling of variceal
      bleeding due to gastric varices. We herein present a unique case of gastric
      variceal bleeding despite cyanoacrilate injection, which was successfully
      controlled with topical ABS application.

PMID- 21868303
TI  - A 63-year-old man with squeezing abdominal pain.

PMID- 21868304
TI  - Prenatal exposure to residential air pollution and infant mental development:
      modulation by antioxidants and detoxification factors.
AB  - BACKGROUND: Air pollution effects on children's neurodevelopment have recently
      been suggested to occur most likely through the oxidative stress pathway.
      OBJECTIVE: We aimed to assess whether prenatal exposure to residential air
      pollution is associated with impaired infant mental development, and whether
      antioxidant/detoxification factors modulate this association. METHODS: In the
      Spanish INfancia y Medio Ambiente (INMA; Environment and Childhood) Project,
      2,644 pregnant women were recruited during their first trimester. Nitrogen
      dioxide (NO2) and benzene were measured with passive samplers covering the study
      areas. Land use regression models were developed for each pollutant to predict
      average outdoor air pollution levels for the entire pregnancy at each residential
      address. Maternal diet was obtained at first trimester through a validated food
      frequency questionnaire. Around 14 months, infant mental development was assessed
      using Bayley Scales of Infant Development. RESULTS: Among the 1,889 children
      included in the analysis, mean exposure during pregnancy was 29.0 MUg/m3 for NO2
      and 1.5 MUg/m3 for benzene. Exposure to NO2 and benzene showed an inverse
      association with mental development, although not statistically significant,
      after adjusting for potential confounders [beta (95% confidence interval) = -0.95
      (-3.90, 1.89) and -1.57 (-3.69, 0.56), respectively, for a doubling of each
      compound]. Stronger inverse associations were estimated for both pollutants among
      infants whose mothers reported low intakes of fruits/vegetables during pregnancy
      [-4.13 (-7.06, -1.21) and -4.37 (-6.89, -1.86) for NO2 and benzene,
      respectively], with little evidence of associations in the high-intake group
      (interaction p-values of 0.073 and 0.047). Inverse associations were also
      stronger in non-breast-fed infants and infants with low maternal vitamin D, but
      effect estimates and interactions were not significant. CONCLUSIONS: Our findings
      suggest that prenatal exposure to residential air pollutants may adversely affect
      infant mental development, but potential effects may be limited to infants whose
      mothers report low antioxidant intakes.

PMID- 21868306
TI  - [Mechanism of E1A-mediated escape from ras-induced senescence in human
      fibraoblasts].
AB  - OBJECTIVE: To study the effect of binding activities of the NH(2) terminus of E1A
      to the proteins regulating cell growth on ras-induced cell senescence and explore
      the mechanism of E1A-mediated escape from ras-induced senescence by E1A in human
      fibroblast. METHODS: In primary human fibroblasts, the proteins regulating cell
      growth in association with E1A NH(2) terminus, including the Rb family proteins,
      p300/CBP, and p400, were inactivated or interfered. The effect of alterations in
      the binding activities of these proteins on cell senescence bypass mediated by
      E1A was evaluated by cell growth curve. RESULTS: The Inactivation of Rb family
      proteins alone was not sufficient to rescue ras-induced cell senescence, whereas
      inactivation of both the Rb proteins and p300/CBP blocked ras-induced senescence
      of human fibroblasts. CONCLUSION: Rb and p300/CBP binding activities are both
      required for E1A to bypass ras-induced senescence in human fibroblasts.

PMID- 21868305
TI  - Biomarkers of methylmercury exposure immunotoxicity among fish consumers in
      Amazonian Brazil.
AB  - BACKGROUND: Mercury (Hg) is a ubiquitous environmental contaminant with
      neurodevelopmental and immune system effects. An informative biomarker of Hg
      induced immunotoxicity could aid studies on the potential contribution to immune
      related health effects. OBJECTIVES: Our objectives were to test the hypothesis
      that methylmercury (MeHg) exposures affect levels of serum biomarkers and to
      examine interactions between Hg and selenium (Se) in terms of these responses.
      METHODS: This cross-sectional epidemiological study assessed adults living along
      the Tapajos River, a system long affected by MeHg. We measured antinuclear (ANA)
      and antinucleolar (ANoA) autoantibody levels and eight cytokines in serum samples
      (n = 232). Total Hg (including MeHg) and Se were measured in blood, plasma, hair,
      and urine. RESULTS: The median (range) total Hg concentrations were 14.1 MUg/g
      (1.1-62.4), 53.5 MUg/L (4.3-288.9), 8.8 MUg/L (0.2-40), and 3.0 MUg/L (0.2-16.1)
      for hair, blood, plasma, and urine, respectively. Elevated titers of ANA (but not
      ANoA) were positively associated with MeHg exposure (log-transformed, for blood
      and plasma), unadjusted [odds ratio (OR) = 2.6; 95% confidence interval (CI):
      1.1, 6.2] and adjusted for sex and age (OR = 2.9; 95% CI: 1.1, 7.5).
      Proinflammatory [interleukin (IL)-6 and interferon (IFN)-gamma], anti
      inflammatory (IL-4), and IL-17 cytokine levels were increased with MeHg exposure;
      however, in the subset of the population with elevated ANA, proinflammatory IL
      1beta, IL-6, IFN-gamma, and tumor necrosis factor (TNF)-alpha and anti
      inflammatory (IL-4) cytokine levels were decreased with MeHg exposure. Although
      Se status was associated with MeHg level (correlation coefficient = 0.86; 95% CI:
      0.29, 1.43), Se status was not associated with any changes in ANA and did not
      modify associations between Hg and ANA titers. CONCLUSIONS: MeHg exposure was
      associated with an increased ANA and changes in serum cytokine profile. Moreover,
      alterations in serum cytokine profiles differed based on ANA response, suggesting
      a specific phenotype of MeHg susceptibility. Further research on the potential
      health implications of these observed immunological changes is warranted.

PMID- 21868307
TI  - Role of asymmetric dimethylarginine in acute lung injury induced by cerebral
      ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: To determine the role of asymmetric dimethylarginine (ADMA) in acute
      lung injury induced by cerebral ischemia/reperfusion (I/R) injury in rats.
      METHODS: Adult male SD rats were randomly divided into 4 groups, namely the sham
      operated group (S), cerebral I/R model group, ADMA+I/R group, and
      dimethylarginine dimethylaminohydrolase (DDAH)+I/R group. In the latter 3 groups,
      acute lung injury was induced by left middle cerebral artery occlusion for 120
      min. After a 24-h reperfusion, the rats were sacrificed and the activities of
      nitric oxide synthase (NOS) and contents of nitric oxide (NO) were measured using
      reductase and colorimetric assay. The mRNA and protein expressions of protein
      kinase C (PKC) and myosin light chain kinase (MLCK) in the lung tissues were
      detected with RT-PCR and Western blotting, respectively. The contents of ADMA in
      the bronchoalveolar lavage fluid (BALF) and blood flowing into and out of the
      lungs were measured by ELISA. RESULTS: Cerebral I/R injury caused significantly
      elevated ADMA levels in the BALF and blood flowing into the lungs, and obviously
      lowered the NO concentration and NOS activity in the lung tissues (P<0.05).
      Following cerebral I/R injury, MLCK and PKC mRNA and protein expressions were
      significantly upregualted in the lung tissues (P<0.05). Exogenous DDAH obviously
      decreased the levels of ADMA in the BALF and blood flowing into the lungs,
      increased NO concentration and NOS activity, and down-regulated MLCK and PKC mRNA
      and protein expressions in lung tissues of rats with cerebral I/R injury
      (P<0.05). CONCLUSION: ADMA contributes to the development of acute lung injury
      following cerebral I/R injury in rats by upregulating MLCK and PKC expression.
      ADMA may serve as a novel therapeutic biomarker and a potential therapeutic
      target for acute lung injury induced by cerebral I/R injury.

PMID- 21868308
TI  - Management of subacute myocardial infarction in a patient with left coronary
      artery originating from the right coronary artery.
AB  - OBJECTIVE: Although the majority of coronary artery anomalies are found
      incidentally and not clinically significant, the interarterial course between the
      major vessels of the aberrant artery may be responsible for syncope, angina,
      arrhythmias or sudden death. There are only a few case reports describing the
      origination of all the coronary arteries from a single ostium. This anomaly
      occurs in only 0.024%-0.044% of the population. Left coronary artery originating
      from the right coronary is a rare coronary abnormality. Here we report a case of
      acute myocardial infarction in a patient with anomalous left coronary artery
      originating from the right coronary artery, as was confirmed by computerized
      tomography angiogram, which showed that only one single coronary artery stem
      originating from the right sinus of Valsalva trifurcated into a right coronary
      artery, left circumflex artery and a hypoplastic left anterior descending artery.
      Subsequent percutaneous coronary intervention (PCI) procedures were performed
      successfully. PCI procedures should be carried out with great caution in such
      cases, and this condition should be managed as a left main lesion.

PMID- 21868309
TI  - [Fas and TNFR1 expressions after cerebral ischemia and reperfusion in rats:
      association with cell apoptosis and the effects of Bcl-2 overexpression].
AB  - OBJECTIVE: To investigate the effect of Bcl-2 overexpression on Fas and TNFR1
      mediated apoptosis and its possible mechanism in rat hippocampus following global
      ischemia/reperfusion (IR). METHODS: Ninety healthy male SD rats were randomly
      divided into sham operated group, IR group and Bcl-2 overexpression group (BT
      group). Rat model of global IR was established by the 4-V0 method. The
      expressions of Bcl-2, Fas and TNFR1 and the cell apoptosis in the CA1 and CA3
      regions were examined by HE staining, immunohistochemistry and TUNEL method.
      RESULTS: In IR group, the neurons in the CA1 region showed an obvious reduction
      in number with disordered arrangement and interstitial edema 48 h after global
      IR. Such changes were not obvious in BT group. Immunohistochemistry showed that
      Fas expression in the CA1 region reached the peak level at 6 h in IR group with a
      greater expression intensity than that in BT group (P<0.05). TNFR1 was expressed
      at a higher level in IR group than in BT group (P<0.05), reaching the peak level
      at 24 h. In the sham group, the expression of Fas and TNFR1 was not detected the
      in CA1 and CA3 regions. Global IR caused increased cell apoptosis in the CA1 and
      CA3 regions, starting at 6 h and reached peak at 24 to 48 h. The cell apoptosis
      was less obvious in BT group (P<0.05). CONCLUSION: Fas and TNFR1 are expressed in
      the CA1 and CA3 regions after global IR in rats, suggesting the involvement of
      death receptor in cerebral IR injury. Bcl-2 overexpression decreases the
      expression of Fas and TNFR1 and cell apoptosis after global IR, thus offering
      protective effect against cerebral IR injury.

PMID- 21868310
TI  - [Role of chloride channels in gambogic acid-induced apoptosis of poorly
      differentiated nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To investigate the role of chloride channels in the apoptosis of
      poorly differentiated nasopharyngeal carcinoma CNE-2Z cells induced by gambogic
      acid (GA). METHODS: MTT assay was applied to detect the proliferation of CNE-2Z
      cells after GA treatment, and the cell apoptosis was detected by Hoechst 33342
      staining. Whole-cell patch clamp technique was employed to record GA-activated
      Cl(-) currents in the cells. RESULTS: GA inhibited the cell proliferation in a
      time- and concentration-dependent manner with an IC(50) of 3.1 umol/L for a 48-h
      treatment. The apoptosis-inducing effect of 8 umol/L GA was attenuated by the
      chloride channel blocker NPPB (100 umol/L) and tamoxifen (20 umol/L). GA induced
      an outward-rectified Cl(-) current in the cells, which was significantly
      inhibited by NPPB. CONCLUSION: GA suppresses cell proliferation and induces
      apoptosis by activating Cl(-) channels in CNE-2Z cells, suggesting the important
      role of Cl(-) channels in GA-induced apoptosis.

PMID- 21868311
TI  - [Feasibility of peptide mass fingerprinting for differential diagnosis of IgA and
      non-IgA nephropathy].
AB  - OBJECTIVE: To investigate the feasibility of peptide mass fingerprinting for non
      invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA
      nephropathy (IgAN).? METHODS: According to the results of renal biopsy, 56
      patients were divided into IgAN group (n=28) and non-IgAN group (n=28), and
      peptide mass fingerprints were acquired from these patients using matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
      RESULTS: Nine different peptides were identified between IgAN and non-IgAN. The
      two most distinctive differentially expressed peptides, with peptide peak values
      of 4476.46 and 1968.10, showed area under curve values of 86.18% and 79.77%.
      Principal component analysis demonstrated that the accumulated explained variance
      of the first 8 differential peptides reached 95%, suggesting the feasibility of
      differential diagnosis of IgAN from non-IgAN. Comparison with the Matrix protein
      database identified the peptide with a relative molecular mass of 5338.08 as a
      fragment of mucin 4 inform and the 2082.77 peptide as fragment of alpha1-II type
      collagen inform. CONCLUSION: MALDI-TOF MS is feasible for differential diagnosis
      of IgAN and non-IgAN and also has great potentials in the classification of the
      subtypes of other systemic diseases.

PMID- 21868312
TI  - [Expression of Caspase-8 and Bcl-2 in the cartilage loose bodies in patients with
      Kashin-Beck disease].
AB  - OBJECTIVE: To investigate the role of Caspase-8 and Bcl-2 in the formation of
      loose bodies in Kashin-Beck disease (KBD). METHODS: Specimens of cartilage loose
      bodies were collected from 50 adult patients with KBD, and the samples of
      articular cartilage were collected from 10 healthy adults to serve as control.
      Avidin-biotin alkaline phosphatase immunohistochemistry was employed to examine
      Bcl-2 and Caspase-8 positivities in the chondrocytes in the loose bodies.
      RESULTS: In KBD loose bodies, the percentage of chondrocytes positive for Bcl-2
      and Caspase-8 [(18.40?8.78)% and (67.54?12.29)%, respectively] were significantly
      higher than those of the control group [(12.25?1.58)% and (24.70?4.35)%,
      respectively]. Caspase-8 was found to promote chondrocyte apoptosis in the loose
      bodies, and this effect overrode the apoptosis-suppressing effect of Bcl-2. Bcl-2
      and Caspase-8 positivities were found mainly in the deep hypertrophic
      chondrocytes in the cartilage or in cells adjacent to the bone tissues.
      CONCLUSION: KBD loose bodies contain an increased percentage of apoptotic
      chondrocytes positive for Bcl-2 and Caspase-8. The apoptosis-inducing effect of
      Caspase-8 was a dominant feature in the cartilage pathology of KBD compared to
      the apoptosis-suppressing effect of Bcl-2.

PMID- 21868313
TI  - [Organotypic slice culture of neonatal rat cortex and induced neural stem cell
      differentiation].
AB  - OBJECTIVE: To establish a method for organotypic slice culture of neonatal rat
      cortex in a modified condition and investigate the effect of spatial signals on
      neural stem cell (NSC) differentiation. METHODS: The brain slices (200 um in
      thickness) of neonatal SD rats (3 to 5 days old) were prepared and cultured in
      modified serum-free DMEM/F12 medium at 37 degrees celsius; with 95% O(2) and 5%
      CO(2). The organotypic slice cultures were observed regularly. NSCs isolated from
      the cortex of rat embryos (14-15 embryonic days) were cultured in serum-free
      DMEM/F12 supplemented with B27 and N2, and the passage 3 NSCs were labeled by CM
      DiI before transplanted onto the organotypic slices cultured for 2 weeks. The
      survival of transplanted NSCs was assessed, and the cell differentiation was
      identified by immunofluorescence staining. RESULTS: The organotypic slice
      cultures were well maintained for at least 4 weeks in the modified medium. The
      thickness of the organotypic slices reduced from 200 um to 130 um after 2-week
      culture in vitro due to the migration of the cells on the edge of the slices. CM
      DiI-labeled NSCs survived well and differentiated into GFAP(+) glia and beta
      tubullin III(+) neurons. CONCLUSION: Neonatal rat organotypic brain slice can be
      successfully cultured in a modified condition to serve as a model for studying
      NSC differentiation induced by spatial signals.

PMID- 21868314
TI  - [Epidermal growth factor stimulates the proliferation of human esophageal
      squamous cell carcinoma HKESC-1 cells by increasing COX-2 expression].
AB  - OBJECTIVE: To investigate the mechanisms responsible for epidermal growth factor
      (EGF)-induced proliferation of human esophageal squamous cell carcinoma cells.
      METHODS: (3)H-thymidine incorporation assay was used to assess the proliferation
      of HKESC-1 cells exposed to EGF stimulation. Enzyme immunoassay was used to
      measure PGE(2) release from HKESC-1 cells, and the protein levels of
      cyclooxygenase 1 (COX-1), COX-2, EP1 and EP2 in EGF-stimulated cells were
      determined by Western blotting. RESULTS: EGF upregulated COX-2 protein expression
      but produced no obvious effect on COX-1 protein expression in HKESC-1 cells. As a
      consequence of increased COX-2, EGF further enhanced cellular PGE(2) release. EGF
      stimulation also resulted in increased protein expression of EP2, a subtype of
      PGE(2) receptors. Both the non-selective COX inhibitor indomethacin and the
      selective COX-2 inhibitor SC-236 completely abolished EGF-induced PGE(2) release,
      and suppressed the mitogenic effect of EGF. CONCLUSION: EGF stimulates the
      proliferation of HKESC-1 cells by increasing COX-2 protein expression and PGE(2)
      release. Upregulated EP2 protein expression may further amplify the mitogenic
      action of PGE(2).

PMID- 21868315
TI  - [Transumbilical laparoendoscopic single-site surgery-assisted vaginal
      hysterectomy: initial report in South China].
AB  - OBJECTIVE: To report the first case of transumbilical laparoendoscopic single
      site surgery-assisted vaginal hysterectomy in South China, and discuss its
      feasibility and safety. METHODS: A 42-year-old woman with multiple myoma of the
      uterus underwent laparoendoscopic single-site surgery-assisted vaginal
      hysterectomy performed using a single multiple-channel port inserted through a
      solitary 2 cm upper umbilicus incision. RESULTS: The total operative time was 3
      h, and duration of the laparoendoscopic procedure was 2 h. The surgery was
      completed uneventfully without an additional port incision or transfer to open
      surgery. The intraoperative blood loss was 100 ml. Bowel peristalsis was
      recovered 3 days after the operation. The vaginal stump and abdominal incision
      healed smoothly without occurrence of vaginal bleeding. CONCLUSION: With the
      development of surgical instruments and improvement of the surgeons' skills,
      laparoendoscopic single-site surgery, due to its invasiveness, can be a promising
      approach to the management of gynecological disease including gynecological
      malignant tumors.

PMID- 21868316
TI  - [Spatiotemporal analysis of event-related potentials during mind wandering].
AB  - OBJECTIVE: To investigate the neural mechanism of mind wandering. METHODS: Event
      related potentials (ERP) was recorded from 10 healthy college students while
      having a sustained attention to response task (SART), which consisted of frequent
      stimuli and rare stimuli with varied probability ratios. The fault response to
      the rare stimulus suggested the occurrence of an episode of mind wandering. The
      ERP of the frequent stimuli before the erroneous or correct responses of the rare
      stimuli were analyzed with two-way ANOVA of repeated-measurement [(wandering:
      yes, no)*(probability ratio: 0.1/0.9, 0.2/0.8, 0.3/0.7)]. RESULTS: The reaction
      time of the error response was shorter than that of the correct one. Significant
      probability effects were also found: the larger the frequent probability, the
      shorter its reaction time and the lower its accuracy. The sensitivity d' had no
      significant effect. The statistical parametric mapping of ERP suggested an
      interaction effect in the bilateral parietal areas (500-600 ms) and frontal areas
      (800-900 ms); the probability effect occurred in the left prefrontal lobe and the
      right parietal lobe (300-350 ms) and mind wandering effect in the bilateral
      occipital lobes (150-350 ms), frontal poles (250-300 ms), bilateral frontal
      temporal-parietal regions (400-600 ms) and left prefrontal (800-900 ms).
      CONCLUSIONS: During mind wandering, the activation of cognitive processing for
      environment information decreases and speedy responses are more common with
      faults. The functional failure of the executive attention system influenced by
      the probability structure of SART may cause the occurrence of mind wandering.

PMID- 21868317
TI  - [Single-port transumbilical laparoscopic cholecystectomy in an adult patient with
      congenital pulmonary hypoplasia: a case report].
AB  - OBJECTIVE: Congenital pulmonary hypoplasia is a rare developmental abnormality of
      the lung with an incidence rate of around 1/5000 000. As a fatal condition
      associated with respiratory insufficiency after birth, this disease is rare in
      adults. We treated a 29-year-old female patient with congenital pulmonary
      hypoplasia and concurrent of cystic duct calculus in May, 2011 using single-port
      transumbilical laparoscopic cholecystectomy, which resulted in a good therapeutic
      effect comparable to that by routine laparoscopic cholecystectomy.

PMID- 21868318
TI  - [Neuron specific enolase gene silencing suppresses proliferation and promotes
      apoptosis of lung cancer cells in vitro].
AB  - OBJECTIVE: To study the effects of neuron specific enolase (NSE) gene silencing
      on the cell proliferation and apoptosis of lung cancer cells in vitro. METHODS:
      NSE protein expression was detected in human small cell lung cancer cell line NCI
      H446 and non-small cell lung cancer cell line A549 by immunocytochemistry, and a
      small interference RNA (siRNA) was transfected into the cells to inhibit NSE gene
      expression. The changes in the cell cycle, apoptosis, Ki67 protein and caspase-3
      activity in the transfected cells were observed by flow cytometry, Western
      blotting and colorimetric assay, respectively. RESULTS: Both A549 and NCI-H446
      cells expressed NSE protein. Transfection of siRNA for NSE gene significantly
      inhibited the expression of NSE gene in the cells, resulting in an inhibition
      rate exceeding 90%. NSE gene silencing caused significantly decreased cell
      percentage in S phase and the expression of Ki67 protein, and increased the cell
      apoptotic rate and caspase-3 activity. CONCLUSION: NSE gene expression promotes
      the cell proliferation and inhibits the cell apoptosis in lung cancer cells with
      neuroendocrine differentiation, which might be a causative factor contributing to
      increased malignancy of the cells.

PMID- 21868319
TI  - [Relationship between visceral fat depot and adiponectin mRNA level in the
      adipose tissue of OLETF rats].
AB  - OBJECTIVE: To investigate the relationship between visceral fat depot and
      adiponectin level in OLETF rats. METHODS: Twenty male OLETF rats and 10 male Long
      Evans Tokushima Otsuka (LETO) rats were subjected to regular oral glucose
      tolerance test (OGTT). The rats were sacrificed at the ages of 8, 32 and 40 weeks
      for measurements of the body weight, blood glucose, blood lipid level, blood
      insulin, and weight of the visceral fat. RESULTS: Compared with LETO rats, OLETF
      rats had significantly higher body weight and visceral fat with impaired glucose
      tolerance (P<0.05). OLETF rats also had higher blood insulin, TG, FFA and CHOL
      levels (P<0.05). The plasma adiponectin level was significantly lower in OLETF
      rats than in LETO rats at different ages (P<0.05). The adiponectin mRNA level in
      the adipose tissue of OLETF rats was comparable with that in LETO rats, but
      significantly decreased at 32 and 40 weeks of age (P<0.01). CONCLUSION: Plasma
      adiponectin level is significantly correlated to insulin sensitivity and visceral
      fat depots in OLETF rats, but a lowered APN mRNA expression level is not the main
      reason for a decreased plasma adiponectin level in the early stage.

PMID- 21868320
TI  - [Effect of Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid on human gastric
      cancer cells and its mechanism].
AB  - OBJECTIVE: To investigate the apoptosis-inducing effect of Ent-11alpha-hydroxy-15
      oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from Pteris semipinnata L
      (PsL), on human gastric cancer SGC7901 cells and explore its mechanism. METHODS:
      The inhibitory effect of 5F on SGC7901 cells was observed by MTT assay and flow
      cytometry, and the changes of the expression of Bcl-2 and Bax in SGC7901 cells
      following 5F exposure were evaluated by Western blot analysis. RESULTS: 5F
      inhibited the proliferation of SGC7901 cells in a concentration- and time
      dependent manner, and the cell apoptosis induced by 5F was confirmed by Annexin V
      EGFP staining and caspase-3 activation assay. The cell apoptosis induced by 5F
      was associated with decreased Bcl-2 and increased Bax expressions. CONCLUSION: 5F
      exposure induces apoptosis in SGC7901 cells by activating mitochondrial apoptotic
      pathways.

PMID- 21868321
TI  - [Effects of high and low shear stress on vascular remodeling and endothelial
      vascular cell adhesion molecular-1 expression in mouse abdominal aorta].
AB  - OBJECTIVE: To establish a mouse model of abdominal aorta stenosis and analyze the
      alterations in the arterial wall response to high and low shear stress. METHODS:
      Twenty mouse were randomized equally into 4 groups, including 3 test groups (1, 7
      and 14 day groups) with surgically induced stenosis of the abdominal aorta, and a
      sham-operated group without stenosis. The hemodynamics and the internal diameter
      of the blood vessel were measured by color Doppler flow imaging. The wall shear
      stress was calculated by Poiseiulle hydrodynamics formula (tau(m)=eta*4*V(m)/D).
      Pathological examination and immunohistochemistry were performed to observe the
      arterial morphological changes and the endothelial vascular cell adhesion
      molecule-1 (VCAM-1) expression. The intimal-media thickness of the aorta was
      measured and endothelial VCAM-1 expression analyzed quantitatively. RESULTS:
      Regions of low and high flow shear stress were created upstream from the stenosis
      and within the stenosis, respectively. Compared with the sham-operated group, the
      mice with aorta stenosis showed gradually increased vascular intimal-media
      thickness and VCAM-1 expression intensity in the upstream aorta, but not within
      the regions of the stenosis. CONCLUSION: Vascular remodeling may occur shortly
      after exposure to low shear stress, which plays a significant role in initiation
      and progression of the pathological process of atherosclerosis mediated by VCAM
      1, whereas high shear stress may exert an anti-atherosclerotic effect.

PMID- 21868322
TI  - [Influence of surface modification of titanium on OPG/RANKL mRNA expression in MG
      63 human osteoblast-like cells].
AB  - OBJECTIVE: To investigate the influence of surface modification of titanium on
      OPG/RANKL mRNA expression in human osteoblast-like cells. METHODS: MG-63
      osteoblast-like cells were seeded on the titanium plates with surface polishing
      and with surface modification by sandblasting plus acid-base treatment, with the
      cells on glass slides as the control. On days 2, 4, 6, and 8 following cell
      seeding, the cells were harvested for examination of OPG/RANKL mRNA expression
      using RT-PCR and real-time PCR. RESULTS: The expression of OPG/RANKL mRNA was
      sensitive to the surface microphotography. Compared with the other groups, the
      cells on the titanium plates with sandblasting plus acid-base treatment, which
      resulted in a porous micro-structure and high roughness, showed significantly up
      regulated expression of OPG mRNA. OPG mRNA expression also showed a time
      dependent up-regulation, and was the highest on day 8. The expression of the
      RANKL mRNA in cells on both of the titanium plates was higher than that in the
      control cells. The peak level of RANKL mRNA expression occurred on day 6 followed
      by a gradual decrease. CONCLUSION: A rough and porous surface of the culture
      plates and prolonged culture time can synergistically up-regulate the ratio of
      OPG/RANKL mRNA.

PMID- 21868323
TI  - [Role of inflammation factors in impaired glucose tolerance and sleep
      apnea/hypopnea syndrome in pregnant women].
AB  - OBJECTIVE: To investigate the possible role of inflammation factors in the
      pathogenesis of impaired glucose tolerance (IGT) with concurrent obstructive
      sleep apnea/hypopnea syndrome (OSAHS) in pregnant women. METHODS: Twenty-five
      pregnant women with IGT and concurrent OSAHS and 35 pregnant women with IGT but
      not OSAHS were monitored for all night polysomnography (PSG), and the apnea
      hypopnea index (AHI) and the lowest pulse oxygen saturation (LSpO2) were
      recorded. The body mass index, glycated serum protein (GSP), interleukin-6 (IL-6)
      and tumor necrosis factor-alpha (TNF-alpha) were measured in these women.
      RESULTS: IL-6 and TNF-alpha levels increased significantly in women with IGT and
      OSAHS as compared with those in women without OSAHS. AHI showed significant
      positive correlations to GSP, IL-6 and TNF-alpha, whereas LSpO2 was inversely
      correlated to GSP, IL-6 and TNF-alpha. IL-6 and TNF-alpha were significantly
      correlated to GSP, with correlation coefficients of 0.510 and 0.476,
      respectively. CONCLUSION: The inflammatory factors may play important roles in
      IGT complicated by OSAHS in pregnant women, and as a potential risk factor, OSAHS
      may contribute to the occurrence of progression of IGT.

PMID- 21868324
TI  - [Plasma interleukin-6 and interleukin-10 levels in different subtypes of lymphoma
      and their clinical significance].
AB  - OBJECTIVE: To study the plasma levels of interleukin6 (IL-6 ) and interleukin10
      (IL-10) in patients with lymphoma and their association with the clinical
      characteristics and prognosis. METHODS: The plasma levels of IL-6 and IL-10 were
      measured in 132 lymphoma patients and 132 healthy controls using enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The levels of plasma IL-6 and IL-10 in
      lymphoma patients were significantly higher than those in healthy controls
      (P<0.05). The plasm a levels of IL-6 were significant higher in T non-Hodgkins
      lymphoma (T-NHL) patients than in B non-Hodgkins lymphoma (B-NHL) patients
      (P<0.05), and were similar between other groups of different subtypes of lymphoma
      (P>0.05). Patients of Kazak nationality had a significantly higher plasma IL-6
      level than those of Han and Uygur nationalities (P<0.05). The presence of B
      symptoms, a high risk defined by the International Prognostic Index (IPI), high
      levels of plasma beta(2)-MG, and elevated LDH and C-reactive protein (CRP) levels
      were all associated with a significantly increased plasma IL-6 level (P<0.05),
      and patients with Ann Arbor stage III-IV disease, B symptoms, and high plasma
      beta(2)-MG and CRP levels had significantly higher IL-10 levels (P<0.05). The
      plasma IL-6 and IL-10 levels were significantly lower in patients with complete
      remission than in those with partial remission and progressive disease and than
      in those without treatment (P<0.05). Plasma IL-10 was positively correlated to IL
      6 and beta(2)-MG levels (P<0.05). CONCLUSION: Lymphoma patients have
      significantly increased plasma IL-6 and IL-10 levels with correlation to the
      tumor load. Plasma levels of IL-6 and IL-10 may serve as useful indicators for
      predicting the response to therapy and prognosis of lymphoma.

PMID- 21868325
TI  - [Endometrial microvessel density for assessing endometrial receptivity during the
      peri-implantation period].
AB  - OBJECTIVE: To evaluate the value of endometrial microvessel density (MVD) in
      assessing the endometrial receptivity during the peri-implantation period.
      METHODS: A total of 104 patients undergoing in vitro fertilization and embryo
      transfer (IVF-ET) treatment were analyzed retrospectively. The subjects were
      divided into clinical pregnancy group (50 cases) and nonpregnant group (54 cases)
      according to the IVF-ET outcome. Endometrial tissues were collected 7 days after
      the natural ovulation prior to IVF-ET for measurement of the endometrial MVD
      using electron microscopy, which was analyzed in relation to the clinical outcome
      of the treatment. RESULTS: The endometrial MVD was significantly higher in the
      clinical pregnancy group than in the nonpregnant group [(4.12?1.84)% vs
      (3.46?1.26)%, t=-2.127, P=0.036). ROC curve analysis showed that the MVD had an
      area under the curve slightly over 0.5 (0.598) for predicting clinical pregnancy,
      suggesting a poor specificity in predicting the clinical outcome of the
      treatment. CONCLUSION: In IVF-ET cycles, the endometrial MVD during the peri
      implantation period is helpful for assessing the endometrial receptivity, but the
      specificity remains low.

PMID- 21868327
TI  - [Role of interleukin-17 and Th17 cells in acute renal allograft rejection in
      mice].
AB  - OBJECTIVE: To investigate the role of Thl7 cells and the cytokine interleukin-17
      (IL-17) in acute allograft rejection in mice. METHODS: Mouse models of kidney
      transplantation were randomly divided into rejection group and isograft group. On
      the post-operative day (POD) 3 and 7, we tested the serum IL-17 level using
      enzyme-linked immunosorbent assay and measured the number of Th17 cells in the
      renal grafts by flow cytometry. The grafts were harvested and fixed in 10%
      formalin to prepare paraffin sections for routine pathological inspection.
      RESULTS: Compared to isograft group, the allograft group showed a significantly
      higher level of serum IL-17 on POD3 and POD7 (P<0.05), and the level of IL-17 is
      significantly higher on POD7 than on POD3 (P<0.05). The allograft group showed
      more infiltrating Th17 cells in the grafts on POD3 and POD7 (P<0.05), and the
      cell number was significantly greater on POD7 (P<0.05). Pathological examination
      also showed an increased severity of graft rejection with the post
      transplantation time. CONCLUSION: Thl7 cells may play an important role in the
      development of renal graft rejection. IL-17 may serve as a potential specific
      indicator for predicting allograft rejection.

PMID- 21868326
TI  - [Construction of rheumatoid arthritis-specific full-length fully human mammalian
      display antibody libraries].
AB  - OBJECTIVE: To construct a rheumatoid arthritis-specific full-length fully human
      mammalian display antibody libraries. METHODS: Peripheral blood lymphocytes were
      isolated from patients with rheumatoid arthritis. The repertoires of kappa light
      chain (LCkappa) and heavy chain variable region (VH) of the antibodies were
      amplified by RT-PCR. The amplified LCkappa and VH genes were inserted into the
      vector pDGB-HC-TM separately, and the ligated libraries were transformed into
      competent E.coli TOPO-10 strain to construct the rheumatoid arthritis-specific
      antibody heavy and light chain libraries. 293T cells were co-transfected with the
      libraries and the full-length fully human antibody expressed on the surface of
      293T cells were analyzed by flow cytometry. RESULTS: The libraries of rheumatoid
      arthritis-specific antibody LCkappa and heavy chain (IgG1) were constructed. The
      expression of full-length fully human antibody on the surface of 293T cells was
      confirmed by flow cytometry. With the rates of correct LCkappa and heavy chain
      sequence insertion reaching 80% and 60%, respectively, as shown by DNA sequence
      analysis of the randomly selected clones, the libraries showed an expressible
      combinatory diversity of 6.13*10(10). CONCLUSION: The constructed libraries
      provide a useful platform for screening rheumatoid arthritis-specific antibodies.

PMID- 21868328
TI  - [Role of the AdeABC efflux pump in carbapenems resistance of clinical isolates of
      Acinetobacter baumannii].
AB  - OBJECTIVE: To investigate the role of AdeABC efflux pump in carbapenems
      resistance of Acinetobacter baumannii in light of the phenotype and genetype of
      the efflux pump. METHODS: The phenotype of the efflux pump was detected in 138
      clinical isolates of A.baumannii using the efflux pump inhibitor carbonyl cyanide
      3-chlorophenylhydrazone (CCCP). The mRNA expression of pump-encoding gene adeB in
      the strains was detected using quantitative real-time RT-PCR. RESULTS: Of the 138
      strains, 28 showed positivities for AdeABC efflux pump identified by Mueller
      Hinton Broth with CCCP. Of the 39 strains resistant to meropenem, 15 (38.4%)
      showed positive results in CCCP assay, a rate significantly higher than that
      among the 99 sensitive strains (13.1%, 13/99) (X(2)=12.477(b), P=0.01). The mRNA
      expression of efflux pump-encoding gene adeB was detected by real-time RT-PCR at
      a level of 0.899??1.172 in meropenem-sensitive strains, significantly lower than
      the level of 21.101??21.443 in meropenem-resistant strains (t=4.403, P=0.000).
      CONCLUSIONS: Efflux plays a role in carbapenems resistance in the clinical
      isolates of A. baumannii. The AdeABC efflux pump may be an important factor in
      reducing carbapenems sensitivity in A. baumannii.

PMID- 21868329
TI  - [Inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine
      ameliorates hemodynamics and pulmonary histopathology in a porcine model of acute
      lung injury].
AB  - OBJECTIVE: To observe the effect of inhalation of aerosolized perfluorocarbon
      combined with tetramethylpyrazine on the hemodynamics and histopathology in a
      porcine model of acute lung injury. METHODS: Normal adult pigs were subjected to
      saline lavage of the bilateral lungs to induce acute lung injury and randomized
      subsequently into 3 groups for treatment with inhalation of perfluorocarbon,
      combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of
      tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP,
      CVP and PAWP were recorded at different time points following the lung injury,
      and the lung tissues were sampled for histological observations. RESULTS: The
      MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute
      lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon
      inhalation significantly improved these indices as compared with inhalation of
      tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology
      was the mildest in the combined inhalation group, and the most severe in
      tetramethylpyrazine group. CONCLUSION: Combined inhalation of perfluorocarbon and
      tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary
      arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

PMID- 21868330
TI  - [On-line detection of hydrocortisone concentration in rat subcutaneous adipose
      with liquid chromatography-mass spectrometry/mass spectrometry].
AB  - OBJECTIVE: To develop a method for detecting the topical concentration of
      hydrocortisone (HC) in the subcutaneous adipose of rats using microdialysis
      sampling technique and liquid chromatography-mass spectrometry/mass spectrometry
      (LC-MS/MS). METHODS: Topical samples were collected by applying the probe into
      the subcutaneous adipose of rats, with alcohol (5%)-ringers solution as the
      perfusion solution. A LC-MS/MS method was established for detecting the HC
      concentration in the dialysates. RESULTS: The protonated precursor to produce ion
      transitions monitored for HC was m/z 363.2->121.1. The calibration curve was
      linear over the range of 0.5-1000 ng/ml, with the intra- and inter-day precision
      and accuracy within ?15%, and no significant matrix effect was noted. The in vivo
      recovery of the probe was about 59%. CONCLUSION: A selective and sensitive method
      has been successfully established for the on-line HC detection in the
      subcutaneous adipose of rats.

PMID- 21868331
TI  - [Human platelet lysates promotes the proliferation of mesenchymal stem cells in
      vitro].
AB  - OBJECTIVE: To investigate the effect of human platelet lysates (HPL) obtained
      from platelet-rich plasma on the proliferation and biological characteristics of
      human mesenchymal stem cells (MSCs) in vitro. METHODS: HPL was obtained by
      repeated freeze-thawing of human plateletes, and the MSCs separated by density
      gradient centrifugation from 6 donors were expanded in medium supplemented with
      10% fetal bovine serum (FCS) or HPL at different concentrations. The optimal
      concentration of HPL for cells culture was determined according to the cell
      proliferation kinetics. The cultured MSCs were characterized for their
      proliferation, cell phenotype, and cell cycle distribution. RESULTS: The HPL
      supplemented medium contained 4 essential growth factors for the growth of MSCs,
      namely platelet-derived growth factors (0.53?0.06 ng/ml), basic fibroblast growth
      factor (37.5?4.31 pg/ml), insulin-like growth factor-1 (0.15?0.06 mg/ml) and
      transforming growth factor (5150?463 pg/ml). Cultured in the presence of HPL at
      the optimal concentration of 7.5%, the MSCs displayed a spindle-shaped fibroblast
      like morphology without obvious changes in the proliferation activity till
      passage 8 (P>0.05), similar to those of cells in FCS-supplemented culture medium.
      Flow cytometry and cell cycle analysis revealed no differences in the phenotypes
      or cell cycle distribution between the cells cultured in the presence of 7.5% HPL
      and 10% FCS. CONCLUSION: The culture medium supplemented by 7.5% HPL can promote
      the expansion of human MSCs and maintain the basic biological characteristics of
      the cells.

PMID- 21868332
TI  - [Effect of willed movement therapy on the expression of neurotrophin 3 and growth
      associated protein 43 in rats with cerebral ischemia reperfusion].
AB  - OBJECTIVE: To observe the effect of willed movement therapy on the expression of
      neurotrophin 3 (NT-3) and growth associated protein 43 (GAP-43) in rats with
      cerebral ischemia-reperfusion (IR) and investigate the neuroprotective mechanism
      of willed movement therapy in nerve regeneration and repair. METHODS: Cerebral IR
      model was established by middle cerebral artery occlusion (MCAO) in SD rats. The
      rats were randomly divided into MCAO group, environment modification group (EM
      group) and willed movement therapy group (WM group). The rats were evaluated for
      neurological deficits and decapitated on days 3, 7 and 15 after the reperfusion
      to examine the expressions of NT-3 and GAP-43 in the ischemic brain tissues by
      immunohistochemistry. RESULTS: Compared with MCAO and EM groups, the rats in WM
      group showed significantly lowered grade of neurological deficits (P<0.05) at 15
      days and significantly increased the expressions of NT-3 and GAP-43 (P<0.05) at 7
      and 15 days after the reperfusion. No significant difference was found in the
      expression of NT-3 and GAP-43 between MCAO and EM groups (P>0.05). The expression
      of NT-3 was positively correlated to that of GAP-43 in the ischemic tissues.
      CONCLUSIONS: Willed movement therapy increases the expression of NT-3 and GAP-43
      in the ischemic brain area in rats with cerebral ischemia-reperfusion, which is
      probably related to nerve regeneration and repair.

PMID- 21868333
TI  - [Effect of losartan on renal expression of monocyte chemoattractant protein-1 and
      transforming growth factor-beta(1) in rats after unilateral ureteral
      obstruction].
AB  - OBJECTIVE: To investigate the effect of losartan on the expression of monocyte
      chemoattractant protein-1 (MCP1) and transforming growth factor-beta(1) (TGF
      beta(1)) in the kidney of rats with unilateral urethral obstruction (UUO) and
      evaluate protective effect of losartan against reanal interstitial fibrosis.
      METHODS: Rat models of UUO were treated with losartan at the routine dose, high
      dose, and very high dose (50, 200, and 500 mg/kg daily, respectively), and saline
      was given to UUO model rats and rats with sham operation. At 7, 14, and 21 days,
      the tail cuff blood pressure (TCP), 24-h urine protein (Upro), serum Scr, BUN,
      K(+), percentage of renal damage and renal interstitial fibrosis (%INT) were
      measured in the rats. MCP1 protein in the renal tissues was detected using
      immunohistochemistry, and MCP1 and TGF-beta(1) mRNA expressions were assayed
      using RT-PCR. RESULTS: As the UUO prolonged, Upro, TCP, tubular damage, %INT, and
      MCP1 and TGF-beta(1) mRNA expressions all increased significantly (P<0.05). High
      and very high doses of losartan, compared with the routine dose, obviously
      reversed these changes. CONCLUSION: High-dose losartan can effectively control
      blood pressure, reduce renal damage and fibrosis, and inhibit MCP1 and TGF
      beta(1) expression in rats with UUO, and at a very high dose, losartan can more
      effectively reduce 24-h Upro than the high-dose group. High and very high doses
      of losartan offer better protective effect on the kidney in rats with UUO.

PMID- 21868334
TI  - [Determination of silver content in silver-loaded coral hydroxyapatite in
      relation to the biocompatibility].
AB  - OBJECTIVE: To determine the amount of silver in silver-loaded coral
      hydroxyapatite (Ag(+)-CHA) bone substitute and its impact on the biocompatibility
      of this material with mouse embryonic osteoblast cells. METHODS: Ag(+)-CHA was
      prepared by immersing coral hydroxyapatite in a serial concentration of silver
      nitrate solutions. The amount of silver in the prepared Ag(+)-CHA was measured by
      inductively coupled plasma atomic emission spectrometry (ICP-AES). The viability
      of MC3T3-E1 cells incubated with Ag(+)-CHA was measured by MTT colorimetric
      assay, and the cell growth and morphological changes were observed by inverted
      phase-contrast microscope and confocal laser scanning microscope. RESULTS: The
      amount of silver loading in the bone substitutes prepared by immersion in 1*10(
      2), 1*10(-3), 5*10(-4), 10(-4), 8*10(-5), and 5*10(-5) mol/L silver nitrate
      solutions were 4127.67?47.35, 167.90?11.00, 83.42?4.51, 30.20?2.32, 22.39?4.09,
      and 15.11?0.55 ug/g, respectively. A low silver content in the material (prepared
      with silver nitrate solution of less than 8*10(-5) mol/L) showed no significant
      inhibitory effect on the growth of MC3T3-E1 cells or produced noticeable
      cytotoxic effect. On the materials prepared with 8*10(-5) and 10(-5) mol/L silver
      nitrate solution, the osteoblasts displayed active proliferation similar to those
      incubated on materials without silver loading. The confluent cells showed a
      normal fusiform morphology with tight arrangement. CONCLUSION: Ag(+)-CHA with low
      silver content has a good biocompability and can promote the proliferation and
      growth of MC3T3-E1 cells in vitro, suggesting the clinical potential of this
      material as a anti-infection bone substitute.

PMID- 21868335
TI  - [Activation of Rho-kinase pathway is involved in angiotensin II-induced
      contraction of human airway smooth muscle cells].
AB  - OBJECTIVE: To investigate of the regulatory effect of Rho-kinase pathway
      activation on angiotensin II (Ang II)-induced contraction of human airway smooth
      muscle cells (HASMCs) in vitro. METHODS: Cultured primary HASMCs were divided
      into control group, AngII group, AngII + irbesartan group and AngII + Y-27632
      group with corresponding treatment. AngII-induced contraction of HASMCs was
      evaluated using collagen gel lattices and observed morphologically using
      immunofluorescence assay. Western Blotting was significantly performed to examine
      the protein expression of Rho-kinase signal pathway. RESULTS: AngII-induced HASMC
      contraction was inhibited by treatments with irbesartan and Y-27632 as shown by
      gel contraction assay (P<0.001). Y-27632 treatment produced a stronger inhibitory
      effect than irbesartan on the expression of phosphorylated moesin, a substrate of
      Rho kinase (P<0.05). CONCLUSION: AngII induces the contraction of HASMCs
      partially as a result of activation of Rho-kinase pathway.

PMID- 21868336
TI  - [GNE gene mutation analysis in 5 patients with distal myopathy with rimmed
      vacuoles].
AB  - OBJECTIVE: To investigate GNE gene mutations in 5 Chinese patients with distal
      myopathy with rimmed vacuoles (DMRV). METHODS: Five patients with typical
      clinical and pathological features of DMRV were studied. All the 11 coding exons
      and the flanking intron sequences of GNE gene were amplified by PCR and
      sequenced. Four family members of case 5 were also examined for GNE gene
      mutations. RESULTS: All the patients were identified to have different GNE gene
      mutations: Cases 1-4 had complex heterozygous mutations and case 5 had homozygous
      mutation. Six reported mutations had been identified, including 1 nonsense
      mutation (p.R8X) and 5 missense mutations (p.D176V, p.I298T, p.A591T, P.A631V,
      and p.V696M). A novel mutation (c.317T>C, p.I106T) was identified in case 2.
      CONCLUSION: This is the first report of p.R8X, p.I298T, p.A591T and p.V696M
      mutations in GNE gene in Chinese population, and a novel mutation p.I106T was
      identified. These findings further expand the clinical and genetic spectrum of
      DMRV in China.

PMID- 21868337
TI  - [Effect of metallothionein on myocyte apoptosis and energy supply of isolated
      rabbit heart muscle during perfusion with ropivacaine].
AB  - OBJECTIVE: [corrected] To assess the effects of metallothionein on myocyte
      apoptosis and energy supply of isolated rabbit heart muscle during perfusion with
      ropivacaine.. METHODS: Sixty New Zealand white male rabbits were randomized into
      3 equal groups. In group I, the rabbits received a intreaperitioneal injection of
      distilled water 24 h before isolation of the heart with perfusion by Langendoff
      model; in group II, distilled water was injected intreaperitioneally, and 24 h
      later the heart was isolated and perfused with Langendoff model and ropivacaine;
      in group III, 3.6% ZnSO(4) was injected intreaperitioneally and the isolated
      heart was perfused with Langendoff model and ropivacaine. The myocardial
      metallothionein content, myocyte apoptosis, and myocardial ATP, ADP and AMP
      content were detected. RESULTS: The myocardial metallothionein content was
      significantly higher in group III than in the other two groups; the percent of
      myocyte apoptosis was the highest in group II, and was significantly higher in
      group III than in group I. The myocardial content of ATP was the highest in group
      I, and was significantly higher in group III than in group II. CONCLUSION:
      Metallothionein can significantly inhibit myocyte apoptosis and alleviate energy
      supply disorder induced by ropivacaine.

PMID- 21868338
TI  - [Factors related to anterior knee pain after total knee arthroplasty].
AB  - OBJECTIVE: To investigate the incidence rate of anterior knee pain after total
      knee arthroplasty (TKA) and identify the related factors. METHODS: This
      prospective, double-blind clinical trial involved a total of 128 patients
      scheduled for primary ipsilateral cemented three-component TKA for
      osteoarthrosis. The patients were randomized into two groups to receive
      operations for TKA with patellar resurfacing (experimental group) or not
      (control). The incidence of anterior knee pain was observed in these patients and
      the factor affecting the occurrence of anterior knee pain and knee was analyzed.
      RESULTS: The patients were followed up for a mean of 16.5 months (range 6~24
      months). The incidence rate of anterior knee pain was 10.9% (7/64) in the
      experimental group, showing no significant difference from the rate of 14.1%
      (9/64) in the control group. But the 52 patients with varus or valgus knee showed
      a significantly higher incidence rate of anterior knee pain (21.2%, 11/52).
      CONCLUSION: TKA with patellar resurfacing can not decrease the incidence of
      anterior knee pain, and varus or valgus before the operation is associated with a
      higher risk of anterior knee pain.

PMID- 21868339
TI  - [Ultracytochemical observation of the intracellular localization of H+-adenosine
      triphosphatase].
AB  - OBJECTIVE: To observe the ultracytochemical localization of H(+)-adenosine
      triphosphatase (H(+)-ATPase) in the cell organelles. METHODS: The localization of
      H(+)-ATPase in the cell organelles was observed in the hepatocytes and renal
      cells of Wistar rats using routine ultracytochemical methods. RESULTS: H(+)
      ATPase activities were observed on the lysosomal membrane and nuclear envelope of
      the hepatocytes and proximal tubule epithelial cells of the nephron in Wistar
      rats. CONCLUSION: This finding supports the hypothesis that H(+)-ATPase (V
      ATPase) is present on the plasma membrane and in the endomembrane system.

PMID- 21868340
TI  - [Expressions of OCT4 and CD133 and their correlation in colonic cancer].
AB  - OBJECTIVE: To investigate the expressions of Oct4 and CD133 and their correlation
      in colonic cancer. METHODS: The expression of Oct4 and CD133 were detected by
      immunohistochemistry in 30 colon cancer specimens and the paired adjacent
      tissues. RESULTS: The positivity rates of Oct4 and CD133 expression were 83.3%
      (25/30) and 73.3% (22/30) in colonic cancer tissue, respectively, and their
      expressions were positively correlated (r=0.586, P<0.05). The matched adjacent
      tissues showed significantly lower levels of Oct4 and CD133 expressions (P<0.01).
      CONCLUSION: The expressions of Oct4 and CD133 are upregulated in colonic cancer
      compared with those in the adjacent tissues and show a positive correlation. Oct4
      and CD133 may play an important role in the development of colon cancer.

PMID- 21868341
TI  - [Prenatal diagnosis of beta-thalassaemia using cell-free fetal DNA in maternal
      plasma].
AB  - OBJECTIVE: To investigate the clinical feasibility of cell-free fetal DNA
      (cffDNA)-based noninvasive prenatal diagnosis of beta-thalassemia. METHODS: Nine
      samples of amniotic fluid were obtained to detect the 8 common and 9 relatively
      rare mutation sites of beta-thalassaemia in Guangdong Province. The maternal
      blood samples were also collected for extracting and purification of the cffDNA,
      and a duplex PCR was performed using 3 pairs of primers and the fetal beta-globin
      genotype was analyzed by reverse dot-blot hybridization. RESULTS: Among the 9
      cases, 5 showed fetal genotypes of beta-thalassemia inherited from the father by
      examination of the amniotic fluid, and 2 fetuses were identified to have beta
      thalassemia genes inherited from the father determined based on the cffDNA in the
      maternal blood. CONCLUSIONS: The cffDNA-based noninvasive prenatal diagnosis is
      feasible for beta-thalassemia, but the contamination of the maternal background
      DNA results in a low detection rate.

PMID- 21868342
TI  - [Kaempferol-induced apoptosis of human esophageal squamous carcinoma Eca-109
      cells and the mechanism].
AB  - OBJECTIVE: To evaluate the growth-inhibiting and pro-apoptotic effect of
      kaempferol in human esophageal squamous carcinoma Eca-109 cells and explore the
      mechanism. METHODS: The effect of kaempferol on Eca-109 cell proliferation in
      vitro was measured by MTT assay. TUNEL staining was used to detect the cell
      apoptosis following kaempferol treatment. The changes in Bax and Bcl-2 mRNA
      expressions in response to kaempferol treatment were determined by RT-PCR, and
      the caspase-3 and caspase-9 activities were evaluated using colorimetric assay.
      RESULTS: Kaempferol significantly inhibited Eca-109 cell proliferation (P<0.05)
      in a concentration-dependent manner and induced obvious cell apoptosis. RT-PCR
      showed that after kaempferol treatment caused up-regulated Bax and down-regulated
      Bcl-2 mRNA expression. The colorimetric assay revealed significantly increased
      caspase-3 and caspase-9 activities in Eca-109 cells following kaempferol
      treatment (P<0.01). CONCLUSION: Kaempferol can induce apoptosis of Eca-109 cells
      via a mitochondria-dependent pathway.

PMID- 21868343
TI  - [Clinical analysis of 8 cases of hepatitis-associated aplastic anemia].
AB  - OBJECTIVE: To study the clinical characteristics of hepatitis-associated aplastic
      anemia (HAAA). A retrospective analysis was conducted among 8 cases of
      established HAAA in light of the clinical and laboratory findings and the patient
      outcomes. METHODS: Serum samples from 8 patients with HAAA were tested for the
      antibodies to hepatitis viruses A, B, C, D, E and CMV, and 7 patients showed
      negative serological results while only one was positive for HBsAg. The
      percentage of CD4(+) cells was significantly lowered while the percentage of
      CD8(+) cells significantly increased to result in a lowered ratio of
      CD4(+)/CD8(+) cells in these HAAA patients. A shift in the Th1/Th2 and Tc1/Tc2
      balance to a Th1 and Tc1 dominance was noted. The percentage of Treg cells was
      obviously decreased. Significant increments were found in the serum levels of
      interleukin-2, THF-alpha and interferon-gamma. Three of the patients responded to
      immunosuppresssive treatment; one patient achieved a complete remission, two had
      a partial remission, and five failed to respond to the therapy and died.
      CONCLUSIONS: HAAA may not have an obvious association with viral infections as by
      hepatitis virus A, B, C, D, or E, and its pathogenesis often involves
      abnormalities of the T cell immunity. Commonly with a poor prognosis, HAAA is
      associated with a high mortality rate.

PMID- 21868344
TI  - [Expression of deleted in liver cancer 1 and phosphorelated focal adhesion kinase
      in breast cancer].
AB  - OBJECTIVE: To analyze the expression of deleted in liver cancer 1 (DLC1) and
      phosphorelated focal adhesion kinase (p-FAK) in breast cancer tissue to further
      understand the molecular mechanisms of the carcinogenesis and metastasis of
      breast cancer. METHODS: Immunohistochemistry was employed to determine the
      protein level of DLC1 and p-FAK in 61 breast cancer, 30 benign breast disease and
      the adjacent normal breast tissues. RESULTS: The positivity rates of DLC1
      differed significantly between breast cancer, benign and normal tissues (34.43%,
      80.00% and 76.67%, respectively, P<0.001). The positivity rates of p-FAK in the 3
      tissues were 77.05%, 33.33% and 26.67%, also showing significant differences
      (P<0.001). The aberrant expression of DLC1 showed an inverse correlation to p-FAK
      (kappa=-0.4591). Both DLC1 and p-FAK were closely correlated to the
      carcinogenesis, clinical stage, PR and lymphatic metastasis of breast cancer
      (P<0.05), but not to the patients age, pathological subtype, familial history, ER
      or CerbB-2 (P>0.05). CONCLUSION: The abnormal expression of DLC1 and p-FAK might
      participate in the carcinogenesis, progression, and metastasis of breast cancer.
      The role of DLC1 and p-FAK might be related to the regulation of progestone. DLC1
      and p-FAK may serve as candidate markers for early diagnosis, prognostic
      evaluation and target treatment of breast cancer.

PMID- 21868345
TI  - [Surgical strategy for ectopic kidneys: analysis of 35 cases].
AB  - OBJECTIVE: To explore the surgical strategy for ectopic kidney and evaluate the
      clinical outcomes. METHODS: From January 2000 to October 2009, 35 cases of
      ectopic kidney were treated surgically in our hospital. Definite diagnoses were
      established in all the cases by ultrasound, intravenous urography (IVU),
      cystoscope, CT, magnetic resonance urography (MRU) and radionuclide imaging
      before the surgery. In these patients, 26 had ipsilateral ectopic ureteral
      orifice (including 5 with bilateral duplicated kidneys and ureter), 9 had
      moderate or severe hydronephrosis (including 3 with ectopic kidney calculi), and
      24 had dysplastic kidney (24/35). All the patients underwent operations,
      including 26 with ectopic nephrectomy, 7 with ectopic ureterovesical
      reimplantation, and 3 with ectopic renal pelvis incision. RESULTS: The clinical
      effect was satisfactory in all the cases during the follow up of 7 to 29 months.
      CONCLUSION: Appropriate surgical approaches according to the concurrent
      deformities and complications can achieve good clinical results in patients with
      ectopic kidneys.

PMID- 21868346
TI  - [Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the
      treatment of HER2-positive advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the safety and efficacy of trsatuzumab (Herceptin)
      combined with FOLFIRI regimen (irinotecan plus 5-FU/LV) in the treatment of HER2
      positive advanced gastric cancer. METHODS: T Thirty-four patients with
      pathologically confirmed advanced gastric cancer, all positive for the human
      epidermal growth factor receptor 2 (HER2) as identified by immunohistochemistry
      and fluorescence in situ hybridization, were randomized into the test group and
      control group to for treatment with the combined regimen and the FOLFIRI regimen
      alone, respectively. FOLFIRI regimen was administered every 2 weeks for 2 to 4
      cycles. Trsatuzumab was given intravenously on a weekly basis with an initial
      dose of 4 mg/kg and a subsequent dose of 2 mg/kg. All the patients were assessed
      for efficacy and toxicity of the treatments. RESULTS: The overall response rate
      was 58.8% in the test group and 35.3% in the control group, with disease control
      rates of 88.2% and 64.7%, respectively, showing significant differences between
      the two groups (P<0.05). The most frequent grade I/II treatment-related adverse
      events included diarrhea, nausea/vomiting and neutropenia. CONCLUSION:
      Trsatuzumab combined with FOLFIRI regimen is effective, safe and well tolerated
      for treatment of HER2-positive advanced gastric cancer.

PMID- 21868347
TI  - [Velocity vector imaging for left ventricular diastolic function assessment and
      the reference values].
AB  - OBJECTIVE: To study value of velocity vector imaging (VVI) in assessment of
      normal left ventricular diastolic function and the corresponding reference
      values. METHODS: Ninety-seven healthy subjects were selected by combined
      clinical, ultrasound, and NT-proBNP examinations. Using a Siemens Acuson Sequoia
      C512 echocardiograph, VVI was adopted to examine the myocardial early diastolic
      velocity (E) of the septal, lateral, anterior, inferior, anterior septum, and
      posterior wall of the left ventricle at the level of mitral annulus. The images
      were analyzed for VVI and the mean diastolic velocity (E(m)) and hence the E/E(m)
      ratio was calculated based on the offline workstation interface. RESULTS: The
      reference range of E/E(m) ratio derived from the data of the 97 healthy subjects
      was (unilateral boundaries with 95% limit) and (1, 22.935), was (1, 22.300) in
      male subjects and (1, 24.766) in female subjects. The reference E/E(m) range was
      (0, 22.413) in male subjects under 50 years of age, (1, 24.766) in female
      subjects under 50 years, (1, 22.300) in male subjects over 50 years, and (1,
      24.766) in female subjects over 50 years. CONCLUSION: VVI is a good method for
      non-invasive evaluation of the left ventricular diastolic function and provides
      an accurate and reliable means for clinical assessment of the left ventricular
      diastolic function.

PMID- 21868348
TI  - [Radioiondine therapy for Graves hyperthyroidism with large goiter: feasibility,
      efficacy and safety].
AB  - OBJECTIVE: To evaluate the feasibility, efficacy and safety of radioiondine
      therapy in the treatment of Graves hyperthyroidism with large goiter. METHODS: A
      total of 128 patients with Graves; hyperthyroidism with large goiter (thyroid
      weight>70 g) as the study group were treated with radioiondine, using 318
      concurrent patients with Graves disease with a smaller goiter (thyroid weight<70
      g) as the control group. The cure rate following a single-session treatment, the
      total cure rate and the incidence of hypothyroidism were compared between the two
      groups. RESULTS: In the large goiter group, the total cure rate was 95.3%, and
      the cure rate following a single-session treatment was 46.9%, with the incidence
      of hypothyroidism of 4.7%, as compared with 90.9%, 65.7%, and 9.1% in the control
      group, respectively. A significant difference was noted in the cure rate
      following a single-session treatment (P=0.000), but not in the total cure rate or
      the incidence of early-onset hypothyroidism (P=0.115) between the two groups. No
      tracheal compression, laryngeal edema, or hyperthyroidism crisis occurred in the
      large goiter group after the treatment. CONCLUSION: Radioiondine is safe and
      effective for treatment of Graves hyperthyroidism with large goiter, and results
      in a total cure rate and incidence of early-onset hypothyroidism similar to those
      in patients with goiters of a smaller size.

PMID- 21868349
TI  - Cool but counterproductive: interactive, Web-based risk communications can
      backfire.
AB  - BACKGROUND: Paper-based patient decision aids generally present risk information
      using numbers and/or static images. However, limited psychological research has
      suggested that when people interactively graph risk information, they process the
      statistics more actively, making the information more available for decision
      making. Such interactive tools could potentially be incorporated in a new
      generation of Web-based decision aids. OBJECTIVE: The objective of our study was
      to investigate whether interactive graphics detailing the risk of side effects of
      two treatments improve knowledge and decision making over standard risk graphics.
      METHODS: A total of 3371 members of a demographically diverse Internet panel
      viewed a hypothetical scenario about two hypothetical treatments for thyroid
      cancer. Each treatment had a chance of causing 1 of 2 side effects, but we
      randomly varied whether one treatment was better on both dimensions (strong
      dominance condition), slightly better on only one dimension (mild dominance
      condition), or better on one dimension but worse on the other (trade-off
      condition) than the other treatment. We also varied whether respondents passively
      viewed the risk information in static pictograph (icon array) images or actively
      manipulated the information by using interactive Flash-based animations of "fill
      in-the-blank" pictographs. Our primary hypothesis was that active manipulation
      would increase respondents' ability to recognize dominance (when available) and
      choose the better treatment. RESULTS: The interactive risk graphic conditions had
      significantly worse survey completion rates (1110/1695, 65.5% vs 1316/1659,
      79.3%, P < .001) than the static image conditions. In addition, respondents using
      interactive graphs were less likely to recognize and select the dominant
      treatment option (234/380, 61.6% vs 343/465, 73.8%, P < .001 in the strong
      dominance condition). CONCLUSIONS: Interactivity, however visually appealing, can
      both add to respondent burden and distract people from understanding relevant
      statistical information. Decision-aid developers need to be aware that
      interactive risk presentations may create worse outcomes than presentations of
      static risk graphic formats.

PMID- 21868350
TI  - MicroRNAs add an additional layer to the complexity of cell signaling.
AB  - MicroRNAs (miRNAs), key posttranscriptional regulators of many biological
      processes, have been implicated in many diseases, including cancer. In a recent
      paper, Avraham and colleagues take a systems biology approach to determine
      whether and how miRNAs are involved in the regulation of oncogenic signaling
      networks downstream of epidermal growth factor (EGF). The authors showed that EGF
      stimulation orchestrated the transcription of both miRNAs and transcription
      factors. An early decrease in the abundance of a subset of miRNAs allowed for the
      induction of messenger RNAs of immediate early genes. Expression of this group of
      miRNAs was also decreased in tumors that showed deregulated signaling through the
      EGF receptor (EGFR) or the related receptor HER2. Their biological properties of
      redundancy, multiplicity, and rapid responsiveness make these small noncoding
      RNAs important regulators of cell signaling.

PMID- 21868352
TI  - Structure of a light-activated LOV protein dimer that regulates transcription.
AB  - Light, oxygen, or voltage (LOV) protein domains are present in many signaling
      proteins in bacteria, archaea, protists, plants, and fungi. The LOV protein VIVID
      (VVD) of the filamentous fungus Neurospora crassa enables the organism to adapt
      to constant or increasing amounts of light and facilitates proper entrainment of
      circadian rhythms. Here, we determined the crystal structure of the fully light
      adapted VVD dimer and reveal the mechanism by which light-driven conformational
      change alters the oligomeric state of the protein. Light-induced formation of a
      cysteinyl-flavin adduct generated a new hydrogen bond network that released the
      amino (N) terminus from the protein core and restructured an acceptor pocket for
      binding of the N terminus on the opposite subunit of the dimer. Substitution of
      residues critical for the switch between the monomeric and the dimeric states of
      the protein had profound effects on light adaptation in Neurospora. The mechanism
      of dimerization of VVD provides molecular details that explain how members of a
      large family of photoreceptors convert light responses to alterations in protein
      protein interactions.

PMID- 21868353
TI  - Focus issue: Cracking the G protein-coupled receptor code.
AB  - As one of the largest and most extensively therapeutically targeted class of
      receptors, G protein-coupled receptors (also known as seven-transmembrane
      receptors) are clinically important regulators of physiology. Research
      highlighted in this issue of Science Signaling provides insight into how receptor
      phosphorylation enables agonists to trigger distinct cellular responses and how
      mutations associated with disease affect receptor responsiveness to ligands. This
      research helps reveal how signaling by these receptors is encoded and decoded to
      produce ligand-specific, cell-specific, and genome-specific responses.

PMID- 21868351
TI  - K2P potassium channels, mysterious and paradoxically exciting.
AB  - New evidence reveals that the common electrolyte disorder hypokalemia can induce
      K2P1 channels that are normally selective for K+ to break the rules and conduct
      Na+. This defiant behavior leads to paradoxical depolarization of many cells in
      the heart, increasing the risk for lethal arrhythmia. The new research resolves a
      mystery uncovered 50 years ago and bestows an array of new riddles. Here, I
      discuss how K2P1 might achieve this alchemy--through stable residence of the K+
      selectivity filter in a Na+-conductive state between its open and C-inactive
      configurations--and predict that other K+ channels and environmental stimuli will
      be discovered to produce the same excitatory misconduct.

PMID- 21868354
TI  - Phosphorylation barcoding as a mechanism of directing GPCR signaling.
AB  - A unifying mechanism by which G protein-coupled receptors (GPCRs) signal in cell
      type-dependent and G protein-independent ways has developed over the past decade.
      GPCR kinases (GRKs) are mediators of homologous desensitization: GRK
      phosphorylation of the receptors leads to the subsequent binding of beta
      arrestins, which partially quenches receptor coupling to G proteins. For some
      receptors, this GRK-mediated phosphorylation stimulates additional signaling
      through the scaffolding action of beta-arrestin. These downstream signals are
      configured by beta-arrestin conformation, which is dictated by the GRK
      phosphoacceptors on the receptors in a barcode-like fashion. Furthermore, each of
      the GRKs can potentially phosphorylate different serine and threonine residues on
      a given receptor, and the phosphorylation pattern can be biased by the receptor
      conformation established by bound ligand. Finally, the arrangement of potential
      GRK phosphorylation sites-and thus the conformation of beta-arrestin and its
      effect on downstream signaling-can differ substantially between even closely
      related GPCRs stimulated by the same agonist. The diversity of the barcoding to
      flexible beta-arrestin explains the multidimensional nature of signaling in the
      superfamily and represents new opportunities for drug discovery.

PMID- 21868355
TI  - beta(2)-Adrenergic receptor polymorphisms and signaling: Do variants influence
      the "memory" of receptor activation?
AB  - Nonsynonymous, coding sequence single-nucleotide polymorphisms in beta(2)
      adrenergic receptors were first recognized almost 20 years ago, but a full
      understanding of their impact on signal transduction-especially on receptor
      abundance in native cells and their clinical importance-remains unclear. New
      evidence has revealed a feature of the Arg(16)Gly variant of beta(2)-adrenergic
      receptors that has not been previously noted: a difference in the rate of
      response upon repeated stimulation of the receptors, such that the Arg(16)
      variant shows slower activation and the Gly(16) variant faster activation of
      cyclic adenosine monophosphate (cAMP) formation-a feature that the authors term
      "receptor memory." This is an intriguing idea but will require confirmation and
      demonstration of its functional importance in vivo and its possible contribution
      to clinical responses, especially in terms of the administration of beta(2)
      adrenergic agonists.

PMID- 21868356
TI  - Intracellular signaling and the origins of the sensations of itch and pain.
AB  - The skin is the largest sensory organ of the body. It is innervated by a diverse
      array of primary sensory neurons, including a heterogeneous subset of
      unmyelinated afferents called C fibers. C fibers, sometimes classified as
      nociceptors, can detect various painful stimuli, including temperature extremes.
      However, it is increasingly evident that these afferents respond to various
      pruritic stimuli and transmit information to the brain that is perceived as itch;
      this can subsequently drive scratching behavior. Although itch and pain are
      distinct sensations, they are closely related and can, under certain
      circumstances, antagonize each other. However, it is not clear precisely when,
      where, and how the processes generating these two sensations originate and how
      they are dissociated. Clues have come from the analysis of the activities of
      specific ligands and their receptors. New data indicate that specific pruritic
      ligands carrying both itch and pain information are selectively recognized by
      different G protein-coupled receptors (GPCRs), and this information may be
      transduced through different intracellular circuits in the same neuron. These
      findings raise questions about the intracellular mechanisms that preprocess and
      perhaps encode GPCR-mediated signals.

PMID- 21868357
TI  - Distinct phosphorylation sites on the beta(2)-adrenergic receptor establish a
      barcode that encodes differential functions of beta-arrestin.
AB  - Phosphorylation of G protein-coupled receptors (GPCRs, which are also known as
      seven-transmembrane spanning receptors) by GPCR kinases (GRKs) plays essential
      roles in the regulation of receptor function by promoting interactions of the
      receptors with beta-arrestins. These multifunctional adaptor proteins desensitize
      GPCRs, by reducing receptor coupling to G proteins and facilitating receptor
      internalization, and mediate GPCR signaling through beta-arrestin-specific
      pathways. Detailed mapping of the phosphorylation sites on GPCRs targeted by
      individual GRKs and an understanding of how these sites regulate the specific
      functional consequences of beta-arrestin engagement may aid in the discovery of
      therapeutic agents targeting individual beta-arrestin functions. The beta(2)
      adrenergic receptor (beta(2)AR) has many serine and threonine residues in the
      carboxyl-terminal tail and the intracellular loops, which are potential sites of
      phosphorylation. We monitored the phosphorylation of the beta(2)AR at specific
      sites upon stimulation with an agonist that promotes signaling by both G protein
      mediated and beta-arrestin-mediated pathways or with a biased ligand that
      promotes signaling only through beta-arrestin-mediated events in the presence of
      the full complement of GRKs or when either GRK2 or GRK6 was depleted. We
      correlated the specific and distinct patterns of receptor phosphorylation by
      individual GRKs with the functions of beta-arrestins and propose that the
      distinct phosphorylation patterns established by different GRKs establish a
      "barcode" that imparts distinct conformations to the recruited beta-arrestin,
      thus regulating its functional activities.

PMID- 21868359
TI  - A polymorphism-specific "memory" mechanism in the beta(2)-adrenergic receptor.
AB  - Signaling through G protein (heterotrimeric guanosine triphosphate-binding
      protein)-coupled receptors is affected by polymorphisms in receptor-encoding
      genes. Using fluorescence resonance energy transfer, we found that the beta(2)
      adrenergic receptor (beta(2)AR) responded to repeated activation with altered
      activation kinetics. Polymorphic variants of the beta(2)AR displayed divergent
      changes of beta(2)AR activation kinetics that closely mimicked their different
      efficacies to generate cyclic adenosine 3',5'-monophosphate. More efficacious
      variants became faster in their activation kinetics, whereas less efficacious
      variants became slower, compared to their initial activation. These differences
      depended on phosphorylation of the receptor by G protein-coupled receptor
      kinases. Our findings suggest an intrinsic, polymorphism-specific property of the
      beta(2)AR that alters activation kinetics upon continued stimulation and that may
      account for individual drug responses.

PMID- 21868358
TI  - Quantitative encoding of the effect of a partial agonist on individual opioid
      receptors by multisite phosphorylation and threshold detection.
AB  - In comparison to endogenous ligands of seven-transmembrane receptors, which
      typically act as full agonists, many drugs act as partial agonists. Partial
      agonism is best described as a "macroscopic" property that is manifest at the
      level of physiological systems or cell populations; however, whether partial
      agonists also encode discrete regulatory information at the "microscopic" level
      of individual receptors is not known. Here, we addressed this question by
      focusing on morphine, a partial agonist drug for MU-type opioid peptide receptors
      (MORs), and by combining quantitative mass spectrometry with cell biological
      analysis to investigate the reduced efficacy of morphine, compared to that of a
      peptide full agonist, in promoting receptor endocytosis. We showed that these
      chemically distinct ligands produced a complex and qualitatively similar mixture
      of phosphorylated opioid receptor forms in intact cells. Quantitatively, however,
      the different agonists promoted disproportionate multisite phosphorylation of a
      specific serine and threonine motif, and we found that modification at more than
      one residue was essential for the efficient recruitment of the adaptor protein
      beta-arrestin that mediated subsequent endocytosis of MORs. Thus, quantitative
      encoding of agonist-selective endocytosis at the level of individual opioid
      receptors was based on the conserved biochemical principles of multisite
      phosphorylation and threshold detection.

PMID- 21868360
TI  - miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to
      mesenchymal transition in breast cancer.
AB  - Compared with the luminal subtype, the basal-like subtype of breast cancer has an
      aggressive clinical behavior, but the reasons for this difference between the two
      subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR
      222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expression
      of epithelial-specific genes and increase expression of mesenchymal-specific
      genes. In addition, expression of these miRNAs increased cell migration and
      invasion, which collectively are characteristics of the epithelial-to-mesenchymal
      transition (EMT). The basal-like transcription factor FOSL1 (also known as Fra-1)
      directly stimulated the transcription of miR-221/222, and the abundance of these
      miRNAs decreased with inhibition of MEK (mitogen-activated or extracellular
      signal-regulated protein kinase kinase), placing miR-221/222 downstream of the
      RAS pathway. The miR-221/222-mediated reduction in E-cadherin abundance depended
      on their targeting of the 3' untranslated region (3'UTR) of TRPS1
      (trichorhinophalangeal syndrome type 1), which is a member of the GATA family of
      transcriptional repressors. TRPS1 inhibited EMT by directly repressing expression
      of ZEB2 (Zinc finger E-box-binding homeobox 2). Therefore, miR-221/222 may
      contribute to the aggressive clinical behavior of basal-like breast cancers.

PMID- 21868361
TI  - Yeast dynamically modify their environment to achieve better mating efficiency.
AB  - The maintenance and detection of signaling gradients are critical for proper
      development and cell migration. In single-cell organisms, gradient detection
      allows cells to orient toward a distant mating partner or nutrient source.
      Budding yeast expand their growth toward mating pheromone gradients through a
      process known as chemotropic growth. MATalpha cells secrete alpha-factor
      pheromone that stimulates chemotropism and mating differentiation in MATa cells
      and vice versa. Paradoxically, MATa cells secrete Bar1, a protease that degrades
      alpha-factor and that attenuates the mating response, yet is also required for
      efficient mating. We observed that MATa cells avoid each other during chemotropic
      growth. To explore this behavior, we developed a computational platform to
      simulate chemotropic growth. Our simulations indicated that the release of Bar1
      enabled individual MATa cells to act as alpha-factor sinks. The simulations
      suggested that the resultant local reshaping of pheromone concentration created
      gradients that were directed away from neighboring MATa cells (self-avoidance)
      and that were increasingly amplified toward partners of the opposite sex during
      elongation. The behavior of Bar1-deficient cells in gradient chambers and mating
      assays supported these predictions from the simulations. Thus, budding yeast
      dynamically remodel their environment to ensure productive responses to an
      external stimulus and avoid nonproductive cell-cell interactions.

PMID- 21868362
TI  - TBK1 mediates crosstalk between the innate immune response and autophagy.
AB  - The autophagic pathway participates in many physiological and pathophysiological
      processes. Autophagy plays an important role, as part of the innate immune
      response, in the first line of defense against intruding pathogens. Recognition
      of pathogens by the autophagic machinery is mainly mediated by autophagic
      adaptors, proteins that simultaneously interact with specific cargos and
      components of the autophagic machinery. However, the exact mechanisms and
      signaling pathways regulating this step are largely unknown. TANK-binding kinase
      1 (TBK1) has been implicated recently in the autophagic clearance of the
      bacterium Salmonella enterica. After its activation by the invading bacteria,
      TBK1 directly phosphorylated the autophagic adaptor optineurin (OPTN). This
      modification led to enhanced interaction of OPTN with the family of mammalian
      Atg8 proteins, which are ubiquitin-like and essential for autophagy. Such
      interaction allows the autophagic machinery to be recruited to the intracellular
      loci of the bacteria, resulting in elimination of the bacteria by lysosomes. This
      study provides an example by which the innate immune response directly regulates
      cargo recruitment into autophagosomes.

PMID- 21868363
TI  - Tumor progression locus 2 mediates signal-induced increases in cytoplasmic
      calcium and cell migration.
AB  - The mitogen-activated protein kinase kinase kinase (MAPKKK or MAP3K) tumor
      progression locus 2 (Tpl2) is required for the transduction of signals initiated
      by the thrombin-activated G protein-coupled receptor (GPCR) protease-activated
      receptor-1 (PAR1), which promote reorganization of the actin cytoskeleton and
      cell migration. Here, we show that Tpl2 is activated through Galpha(i2)
      transduced GPCR signals. Activated Tpl2 promoted the phosphorylation and
      activation of phospholipase C-beta3 (PLCbeta(3)); consequently, Tpl2 was required
      for thrombin-dependent production of inositol 1,4,5-trisphosphate (IP(3)), IP(3)
      mediated cytoplasmic calcium ion (Ca(2+)) signals, and the activation of
      classical and novel members of the protein kinase C (PKC) family. A PKC-mediated
      feedback loop facilitated extracellular signal-regulated kinase (ERK) activation
      in response to Tpl2 and contributed to the coordinate regulation of the ERK and
      Ca(2+) signaling pathways. Pharmacological and genetic studies revealed that
      stimulation of cell migration by Tpl2 depends on both of these pathways. Tpl2
      also promoted Ca(2+) signals and cell migration from sphingosine 1-phosphate
      responsive GPCRs, which also couple to Galpha(i); from Wnt5a; and from the
      interleukin-1beta (IL-1beta) receptor, a member of the Toll-IL-1R (TIR) domain
      family. Our data provide new insights into the role of Tpl2 in GPCR-mediated
      Ca(2+) signaling and cell migration.

PMID- 21868364
TI  - A signaling loop of REST, TSC2 and beta-catenin governs proliferation and
      function of PC12 neural cells.
AB  - The RE-1-specific silencing transcription factor (REST or NRSF) is a
      transcription repressor that orchestrates differentiation and also operates in
      differentiated neurons and neurosecretory cells (neural cells). Its role in
      proliferation has been investigated so far only in rapidly growing tumors, with
      conflicting results: suppression in non-neural tumors, stimulation in
      medulloblastomas. Working with two clones of chromaffin-neuronal PC12 cells,
      which express different levels of REST, and using genetic complementation and
      knockdown approaches, we show that REST also promotes proliferation in
      differentiated neural cells. Mechanistically, this occurs by a signaling pathway
      involving REST, the GTPase-activating protein tuberin (TSC2) and the
      transcription co-factor beta-catenin. In PC12 cells, raised expression of REST
      correlates with reduced TSC2 levels, nuclear accumulation and co-transcriptional
      activation of beta-catenin, and increased expression of its target oncogenes Myc
      and Ccnd1, which might account for the proliferation advantage and the distinct
      morphology. Rest transcription is also increased, unveiling the existence of a
      self-sustaining, feed-forward REST-TSC2-beta-catenin signaling loop that is also
      operative in another neural cell model, NT2/D1 cells. Transfection of REST,
      knockdown of TSC2 or forced expression of active beta-catenin recapitulated the
      biochemical, functional and morphological properties of the high-expressing REST
      clone in wild-type PC12 cells. Upregulation of REST promoted proliferation and
      phenotypic changes, thus hindering neurosecretion. The new REST-TSC2-beta-catenin
      signaling paradigm might have an important role in various aspects of neural cell
      physiology and pathology, including the regulation of proliferation and
      neurosecretion.

PMID- 21868365
TI  - Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires
      activation of the epidermal growth factor receptor.
AB  - Fibroblast growth factor receptor 1 (FGFR1) is an oncoprotein with known
      involvement in mammary tumorigenesis. To understand how FGFR1 signaling promotes
      mammary tumorigenesis, an inducible FGFR1 (iFGFR1) system was created previously.
      Previous studies have demonstrated that upon iFGFR1 activation in vivo, the
      epidermal growth factor (EGF) ligands amphiregulin (AREG) and epiregulin (EREG)
      are upregulated. Both AREG and EREG interact with the EGF receptor (EGFR). Here,
      we investigated whether the FGFR1-induced increase in AREG and EREG expression
      might coordinately increase EGFR signaling to promote mammary tumorigenesis.
      Treatment of mouse mammary epithelial cells with either AREG or EREG conferred a
      greater migratory potential, increased cellular proliferation and increased
      extracellular regulated kinase 1/2 (ERK1/2) activation. These effects could be
      blocked with the EGFR-specific inhibitor erlotinib, suggesting that they are EGFR
      dependent. In transgenic mice with iFGFR1 under the control of the mouse mammary
      tumor virus (MMTV) promoter, iFGFR1 activation also led to increased mammary
      epithelial cell proliferation that was inhibited with erlotinib. Taken together,
      these data suggest that AREG and EREG mediate tumorigenic phenotypes by
      activating EGFR signaling, and that the oncogenic potential of FGFR1 requires
      EGFR activation to promote mammary tumorigenesis.

PMID- 21868366
TI  - A new regulatory function of the region proximal to the RGG box in the fragile X
      mental retardation protein.
AB  - Fragile X mental retardation protein (FMRP) is required for normal cognition.
      FMRP has two autosomal paralogs, which although similar to FMRP, cannot
      compensate for the loss of FMRP expression in brain. The arginine- and glycine
      rich region of FMRP (the RGG box) is unique; it is the high-affinity RNA-binding
      motif in FMRP and is encoded by exon 15. Alternative splicing occurs in the 5'
      end of exon 15, which is predicted to affect the structure of the distally
      encoded RGG box. Here, we provide evidence that isoform 3, which removes 25 amino
      acids from the 5' end of exon 15, has an altered conformation that reduces
      binding of a specific antibody and renders the RGG box unable to efficiently
      associate with polyribosomes. Isoform 3 is also compromised in its ability to
      form granules and to associate with a key messenger ribonucleoprotein Yb1 (also
      known as p50, NSEP1 and YBX1). Significantly, these functions are similarly
      compromised when the RGG box is absent from FMRP, suggesting an important
      regulatory role of the N-terminal region encoded by exon 15.

PMID- 21868367
TI  - Strategies of professional phagocytes in vivo: unlike macrophages, neutrophils
      engulf only surface-associated microbes.
AB  - The early control of potentially invading microbes by our immune system primarily
      depends on its main professional phagocytes - macrophages and neutrophils.
      Although the different functions of these two cell types have been extensively
      studied, little is known about their respective contributions to the initial
      control of invading microorganisms before the onset of adaptive immune responses.
      The naturally translucent zebrafish larva has recently emerged as a powerful
      model vertebrate in which to visualise the dynamic interactions between
      leukocytes and microbes in vivo. Using high-resolution live imaging, we found
      that whereas macrophages efficiently engulf bacteria from blood or fluid-filled
      body cavities, neutrophils barely do so. By contrast, neutrophils very
      efficiently sweep up surface-associated, but not fluid-borne, bacteria. Thus the
      physical presentation of unopsonised microbes is a crucial determinant of
      neutrophil phagocytic ability. Neutrophils engulf microbes only as they move over
      them, in a 'vacuum-cleaner' type of behaviour. This context-dependent nature of
      phagocytosis by neutrophils should be of particular relevance to human infectious
      diseases, especially for the early phase of encounter with microbes new to the
      host.

PMID- 21868368
TI  - Dynamic remodeling of the actin cytoskeleton by FMNL1gamma is required for
      structural maintenance of the Golgi complex.
AB  - Formin-like 1 (FMNL1) is a member of the formin family of actin nucleators, and
      is one of the few formins for which in vitro activities have been well
      characterized. However, the functional roles of this mammalian formin remain ill
      defined. In particular, it is unclear how the unique in vitro biochemical
      properties of FMNL1 relate to its regulation of cellular processes. Here, we
      demonstrate that FMNL1 depletion caused a dramatic increase in cellular F-actin
      content, which resulted in Golgi complex fragmentation. Moreover, increased F
      actin and maintenance of Golgi structure were distinctly regulated by the gamma
      isoform of FMNL1, which required binding to actin. Importantly, in addition to
      Golgi fragmentation, increased F-actin content in the absence of FMNL1 also led
      to cation-independent mannose 6-phosphate receptor dispersal, lysosomal
      enlargement and missorting of cathepsin D. Taken together, our data support a
      model in which FMNL1 regulates cellular F-actin levels required to maintain
      structural integrity of the Golgi complex and lysosomes.

PMID- 21868369
TI  - Treatment of sydenham chorea with intravenous immunoglobulin.
AB  - Sydenham chorea is a post-streptococcal, autoimmune, neuropsychiatric, movement
      disorder. There is no effective treatment. In a randomized study, comparison was
      made of the outcomes of 10 children treated with standard management alone
      compared to 10 who received additional intravenous immunoglobulin. The outcomes
      were assessed using a clinical rating scale, brain single-photon emission
      computed tomography, and the duration of symptomatic treatment. All three outcome
      measurement tools found improved outcomes in the group that received intravenous
      immunoglobulin.

PMID- 21868370
TI  - Impaired social behavior in children with benign childhood epilepsy with
      centrotemporal spikes.
AB  - The aim of the present study was to assess the emotional and cognitive aspects of
      social cognition among patients with rolandic epilepsy. A computerized
      neuropsychological battery was used for cognitive evaluation. Affective and
      cognitive social cognition were evaluated using two computerized Theory of Mind
      tasks. Cognitive abilities and social behavior of 15 children, diagnosed with
      rolandic epilepsy, ages 7 to 13 years were assessed and compared with 15 age- and
      education-matched healthy controls. Compared with controls, the epileptic
      patients had lower scores on verbal and visual learning rate parameters and on
      verbal processing and were significantly impaired on "affective Theory of Mind"
      tasks but not on "cognitive Theory of Mind" conditions. Our findings raise the
      possibility that rolandic epilepsy may affect neural networks affecting cognition
      and mediating social cognition essential for social behavior, thus challenging
      the benign nature of the condition.

PMID- 21868371
TI  - Arterial ischemic stroke in an adolescent with presumed perinatal ischemic
      stroke.
AB  - The risk of recurrent ischemic stroke after presumed perinatal stroke and the
      risk factors for such recurrence are rarely reported. Here, we present an
      adolescent with a history of presumed perinatal stroke who presented with
      arterial ischemic stroke recurrence at the age of 15 years. Hereditary
      thrombophilia screening performed at the time of his stroke recurrence
      demonstrated protein S deficiency. No evidence-based consensus guidelines on
      thrombophilia screening in children with presumed perinatal stroke exist, nor has
      the role of secondary prophylaxis been addressed. There is a risk of stroke
      recurrence after presumed perinatal stroke, and routine thrombophilia screening
      may identify those children who are at higher risk for recurrence and who might
      therefore benefit from secondary prophylaxis. Clear guidelines should be
      developed to standardize investigations and management of children with presumed
      perinatal ischemic stroke.

PMID- 21868372
TI  - Folinic acid supplementation in Rett syndrome patients does not influence the
      course of the disease: a randomized study.
AB  - Rett syndrome is a neurodevelopmental disorder in girls, related to mutations in
      MECP2 gene. It has been postulated that low 5-methyltetrahydrofolate (5-MTHF)
      levels are present in cerebrospinal fluid. Folinic acid demonstrated clinical
      improvement. However, because studies have produced conflicting results, we
      performed a randomized, double-blind crossover, long-term, follow-up study on
      folinic acid. Eight Rett syndrome patients received both folinic acid and
      placebo, for 1 year each. Measurements included plasma folate, 5-MTHF, and
      clinical outcome scores like Rett Syndrome Motor Behavioral Assessment, Hand
      Apraxia Scale, and the parental Overall Well-Being Index. In 2 patients, low 5
      MTHF levels were present. Folinic acid supplementation increased cerebrospinal
      fluid 5-MTHF levels, but with no objective evidence of clinical improvement. The
      Overall Well-Being Index showed a significant difference in favor of folinic
      acid, not confirmed objectively. In our double-blind randomized study, folinic
      acid supplementation resulted in increased 5-MTHF levels, but with no objective
      signs of clinical improvement.

PMID- 21868373
TI  - Re: "problems with risk reclassification methods for evaluating prediction
      models".

PMID- 21868374
TI  - Obesity and cannabis use: results from 2 representative national surveys.
AB  - The role of cannabis and endocannabinoids in appetite regulation has been
      extensively studied, but the association of cannabis use with weight in the
      general population is not known. The authors used data from 2 representative
      epidemiologic studies of US adults aged 18 years or older, the National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002) and
      the National Comorbidity Survey-Replication (NCS-R; 2001-2003), to estimate the
      prevalence of obesity as a function of cannabis use. The adjusted prevalences of
      obesity in the NESARC and the NCS-R were 22.0% and 25.3%, respectively, among
      participants reporting no use of cannabis in the past 12 months and 14.3% and
      17.2%, respectively, among participants reporting the use of cannabis at least 3
      days per week. These differences were not accounted for by tobacco smoking
      status. Additionally, after adjustment for sex and age, the use of cannabis was
      associated with body mass index differences in both samples. The authors conclude
      that the prevalence of obesity is lower in cannabis users than in nonusers.

PMID- 21868376
TI  - The consensus sequence for self-catalyzed site-specific G residue depurination in
      DNA.
AB  - The sequence variation tolerated within the stem-loop-forming genomic consensus
      sequence for self-catalyzed site-specific depurination of G residues is explored.
      The variation in self-depurination kinetics with sequence changes in the loop
      residues and stem base pairs, as well as with pH, provides insights into the self
      catalytic mechanism. The observations suggest that self-catalyzed depurination of
      the 5' G residue of the loop consensus sequence 5'-G(T/A)GG-3' probably involves
      formation of some intraloop hydrogen-bonded base pair with the 3'-terminal G
      residue; although the electronic structure of both these G residues is retained,
      their 2-amino substituents are not critical for that interaction. The strong
      dependence of the self-depurination kinetics on stem stability suggests that the
      lifetime of some strained form of the loop is controlled by the integrity of the
      stem. In addition to the effects of length and base pair sequence on stem
      stability, there is a base pair requirement at the base of the loop: self
      depurination is suppressed by 5'-C.G-3', 5'-A.T-3', or a mismatch but is most
      favored by 5'T.A3' and less so by 5'-G.C-3'. The occurrence in T and G of a
      similarly located carbonyl capable of hydrogen-bonding to the water molecule
      required for glycosyl bond hydrolysis may explain this sequence requirement. In
      toto, the more complete definition of the consensus sequence provided by this
      investigation enables a more accurate estimation of their number in the human
      genome and their distribution among different genes.

PMID- 21868375
TI  - Self-catalyzed site-specific depurination of G residues mediated by cruciform
      extrusion in closed circular DNA plasmids.
AB  - A major variety of "spontaneous" genomic damage is endogenous generation of
      apurinic sites. Depurination rates vary widely across genomes, occurring with
      higher frequency at "depurination hot spots." Recently, we discovered a site
      specific self-catalyzed depurinating activity in short (14-18 nucleotides) DNA
      stem-loop-forming sequences with a 5'-G(T/A)GG-3' loop and T.A or G.C as the
      first base pair at the base of the loop; the 5'-G residue of the loop self
      depurinates at least 10(5)-fold faster than random "spontaneous" depurination at
      pH 5. Formation of the catalytic intermediate for self-depurination in double
      stranded DNA requires a stem-loop to extrude as part of a cruciform. In this
      study, evidence is presented for self-catalyzed depurination mediated by
      cruciform formation in plasmid DNA in vitro. Cruciform extrusion was confirmed,
      and its extent was quantitated by digestion of the plasmid with single strand
      specific mung bean endonuclease, followed by restriction digestion and sequencing
      of resulting mung bean-generated fragments. Appearance of the apurinic site in
      the self-depurinating stem-loop was confirmed by digestion of plasmid DNA with
      apurinic endonuclease IV, followed by primer extension and/or PCR amplification
      to detect the endonuclease-generated strand break and identify its location. Self
      catalyzed depurination was contingent on the plasmid being supercoiled and was
      not observed in linearized plasmids, consistent with the presence of the extruded
      cruciform in the supercoiled plasmid and not in the linear one. These results
      indicate that self-catalyzed depurination is not unique to single-stranded DNA;
      rather, it can occur in stem-loop structures extruding from double-stranded DNA
      and therefore could, in principle, occur in vivo.

PMID- 21868377
TI  - Dexamethasone enhances 1alpha,25-dihydroxyvitamin D3 effects by increasing
      vitamin D receptor transcription.
AB  - Calcitriol, the active form of vitamin D, in combination with the glucocorticoid
      dexamethasone (Dex) has been shown to increase the antitumor effects of
      calcitriol in squamous cell carcinoma. In this study we found that pretreatment
      with Dex potentiates calcitriol effects by inhibiting cell growth and increasing
      vitamin D receptor (VDR) and VDR-mediated transcription. Treatment with
      actinomycin D inhibits Vdr mRNA synthesis, indicating that Dex regulates VDR
      expression at transcriptional level. Real time PCR shows that treatment with Dex
      increases Vdr transcripts in a time- and a dose-dependent manner, indicating that
      Dex directly regulates expression of Vdr. RU486, an inhibitor of glucocorticoids,
      inhibits Dex-induced Vdr expression. In addition, the silencing of glucocorticoid
      receptor (GR) abolishes the induction of Vdr by Dex, indicating that Dex
      increases Vdr transcripts in a GR-dependent manner. A fragment located 5.2 kb
      upstream of Vdr transcription start site containing two putative glucocorticoid
      response elements (GREs) was evaluated using a luciferase-based reporter assay.
      Treatment with 100 nm Dex induces transcription of luciferase driven by the
      fragment. Deletion of the GRE distal to transcription start site was sufficient
      to abolish Dex induction of luciferase. Also, chromatin immunoprecipitation
      reveals recruitment of GR to distal GRE with Dex treatment. We conclude that Dex
      increases VDR and vitamin D effects by increasing Vdr de novo transcription in a
      GR-dependent manner.

PMID- 21868378
TI  - Lysine 624 of the amyloid precursor protein (APP) is a critical determinant of
      amyloid beta peptide length: support for a sequential model of gamma-secretase
      intramembrane proteolysis and regulation by the amyloid beta precursor protein
      (APP) juxtamembrane region.
AB  - gamma-Secretase is a multiprotein intramembrane cleaving aspartyl protease (I
      CLiP) that catalyzes the final cleavage of the amyloid beta precursor protein
      (APP) to release the amyloid beta peptide (Abeta). Abeta is the primary component
      of senile plaques in Alzheimer's disease (AD), and its mechanism of production
      has been studied intensely. gamma-Secretase executes multiple cleavages within
      the transmembrane domain of APP, with cleavages producing Abeta and the APP
      intracellular domain (AICD), referred to as gamma and epsilon, respectively. The
      heterogeneous nature of the gamma cleavage that produces various Abeta peptides
      is highly relevant to AD, as increased production of Abeta 1-42 is genetically
      and biochemically linked to the development of AD. We have identified an amino
      acid in the juxtamembrane region of APP, lysine 624, on the basis of APP695
      numbering (position 28 relative to Abeta) that plays a critical role in
      determining the final length of Abeta peptides released by gamma-secretase.
      Mutation of this lysine to alanine (K28A) shifts the primary site of gamma
      secretase cleavage from 1-40 to 1-33 without significant changes to epsilon
      cleavage. These results further support a model where epsilon cleavage occurs
      first, followed by sequential proteolysis of the remaining transmembrane
      fragment, but extend these observations by demonstrating that charged residues at
      the luminal boundary of the APP transmembrane domain limit processivity of gamma
      secretase.

PMID- 21868379
TI  - Transcriptional regulation of S phase kinase-associated protein 2 by NR4A orphan
      nuclear receptor NOR1 in vascular smooth muscle cells.
AB  - Members of the NR4A subgroup of the nuclear hormone receptor superfamily have
      emerged as key transcriptional regulators of proliferation and inflammation. NOR1
      constitutes a ligand-independent transcription factor of this subgroup and
      induces cell proliferation; however, the transcriptional mechanisms underlying
      this mitogenic role remain to be defined. Here, we demonstrate that the F-box
      protein SKP2 (S phase kinase-associated protein 2), the substrate-specific
      receptor of the ubiquitin ligase responsible for the degradation of p27(KIP1)
      through the proteasome pathway, constitutes a direct transcriptional target for
      NOR1. Mitogen-induced Skp2 expression is silenced in vascular smooth muscle cells
      (VSMC) isolated from Nor1-deficient mice or transfected with Nor1 siRNA.
      Conversely, adenovirus-mediated overexpression of NOR1 induces Skp2 expression in
      VSMC and decreases protein abundance of its target p27. Transient transfection
      experiments establish that NOR1 transactivates the Skp2 promoter through a nerve
      growth factor-induced clone B response element (NBRE). Electrophoretic mobility
      shift and chromatin immunoprecipitation assays further revealed that NOR1 is
      recruited to this NBRE site in the Skp2 promoter in response to mitogenic
      stimulation. In vivo Skp2 expression is increased during the proliferative
      response underlying neointima formation, and this transcriptional induction
      depends on the expression of NOR1. Finally, we demonstrate that overexpression of
      Skp2 rescues the proliferative arrest of Nor1-deficient VSMC. Collectively, these
      results characterize Skp2 as a novel NOR1-regulated target gene and detail a
      previously unrecognized transcriptional cascade regulating mitogen-induced VSMC
      proliferation.

PMID- 21868380
TI  - Substrate sequence influences gamma-secretase modulator activity, role of the
      transmembrane domain of the amyloid precursor protein.
AB  - A subset of non-steroidal anti-inflammatory drugs modulates the gamma cleavage
      site in the amyloid precursor protein (APP) to selectively reduce production of
      Abeta42. It is unclear precisely how these gamma-secretase modulators (GSMs) act
      to preferentially spare Abeta40 production as well as Notch processing and
      signaling. In an effort to determine the substrate requirements in NSAID/GSM
      activity, we determined the effects of sulindac sulfide and flurbiprofen on gamma
      cleavage of artificial constructs containing several gamma-secretase substrates.
      Using FLAG-tagged constructs that expressed extracellularly truncated APP, Notch
      1, or CD44, we found that these substrates have different sensitivities to
      sulindac sulfide. gamma-Secretase cleavage of APP was altered by sulindac
      sulfide, but CD44 and Notch-1 were either insensitive or only minimally altered
      by this compound. Using chimeric APP constructs, we observed that the
      transmembrane domain (TMD) of APP played a pivotal role in determining drug
      sensitivity. Substituting the APP TMD with that of APLP2 retained the sensitivity
      to gamma-cleavage modulation, but replacing TMDs from Notch-1 or ErbB4 rendered
      the resultant molecules insensitive to drug treatment. Specifically, the GXXXG
      motif within APP appeared to be critical to GSM activity. Consequently, the
      modulatory effects on gamma-cleavage appears to be substrate-dependent. We
      hypothesize that the substrate present in the gamma-secretase complex influences
      the conformation of the complex so that the binding site of GSMs is either
      stabilized or less favorable to influence the cleavage of the respective
      substrates.

PMID- 21868381
TI  - Sources of cell-to-cell variability in canonical nuclear factor-kappaB (NF
      kappaB) signaling pathway inferred from single cell dynamic images.
AB  - The canonical nuclear factor-kappaB (NF-kappaB) signaling pathway controls a gene
      network important in the cellular inflammatory response. Upon activation, NF
      kappaB/RelA is released from cytoplasmic inhibitors, from where it translocates
      into the nucleus, subsequently activating negative feedback loops producing
      either monophasic or damped oscillatory nucleo-cytoplasmic dynamics. Although the
      population behavior of the NF-kappaB pathway has been extensively modeled, the
      sources of cell-to-cell variability are not well understood. We describe an
      integrated experimental-computational analysis of NF-kappaB/RelA translocation in
      a validated cell model exhibiting monophasic dynamics. Quantitative measures of
      cellular geometry and total cytoplasmic concentration and translocated RelA
      amounts were used as priors in Bayesian inference to estimate biophysically
      realistic parameter values based on dynamic live cell imaging studies of enhanced
      GFP-tagged RelA in stable transfectants. Bayesian inference was performed on
      multiple cells simultaneously, assuming identical reaction rate parameters,
      whereas cellular geometry and initial and total NF-kappaB concentration-related
      parameters were cell-specific. A subpopulation of cells exhibiting distinct
      kinetic profiles was identified that corresponded to differences in the
      IkappaBalpha translation rate. We conclude that cellular geometry, initial and
      total NF-kappaB concentration, IkappaBalpha translation, and IkappaBalpha
      degradation rates account for distinct cell-to-cell differences in canonical NF
      kappaB translocation dynamics.

PMID- 21868382
TI  - Reactions of beta-propiolactone with nucleobase analogues, nucleosides, and
      peptides: implications for the inactivation of viruses.
AB  - beta-Propiolactone is often applied for inactivation of viruses and preparation
      of viral vaccines. However, the exact nature of the reactions of beta
      propiolactone with viral components is largely unknown. The purpose of the
      current study was to elucidate the chemical modifications occurring on
      nucleotides and amino acid residues caused by beta-propiolactone. Therefore, a
      set of nucleobase analogues was treated with beta-propiolactone, and reaction
      products were identified and quantified. NMR revealed at least one modification
      in either deoxyguanosine, deoxyadenosine, or cytidine after treatment with beta
      propiolactone. However, no reaction products were found from thymidine and
      uracil. The most reactive sides of the nucleobase analogues and nucleosides were
      identified by NMR. Furthermore, a series of synthetic peptides was used to
      determine the conversion of reactive amino acid residues by liquid chromatography
      mass spectrometry. beta-Propiolactone was shown to react with nine different
      amino acid residues. The most reactive residues are cysteine, methionine, and
      histidine and, to a lesser degree, aspartic acid, glutamic acid, tyrosine,
      lysine, serine, and threonine. Remarkably, cystine residues (disulfide groups) do
      not react with beta-propiolactone. In addition, no reaction was observed for beta
      propiolactone with asparagine, glutamine, and tryptophan residues. beta
      Propiolactone modifies proteins to a larger extent than expected from current
      literature. In conclusion, the study determined the reactivity of beta
      propiolactone with nucleobase analogues, nucleosides, and amino acid residues and
      elucidated the chemical structures of the reaction products. The study provides
      detailed knowledge on the chemistry of beta-propiolactone inactivation of
      viruses.

PMID- 21868383
TI  - LIM kinase has a dual role in regulating lamellipodium extension by decelerating
      the rate of actin retrograde flow and the rate of actin polymerization.
AB  - Lamellipodium extension is crucial for cell migration and spreading. The rate of
      lamellipodium extension is determined by the balance between the rate of actin
      polymerization and the rate of actin retrograde flow. LIM kinase 1 (LIMK1)
      regulates actin dynamics by phosphorylating and inactivating cofilin, an actin
      depolymerizing protein. We examined the role of LIMK1 in lamellipodium extension
      by measuring the rates of actin polymerization, actin retrograde flow, and
      lamellipodium extension using time-lapse imaging of fluorescence recovery after
      photobleaching. In the non-extending lamellipodia of active Rac-expressing N1E
      115 cells, LIMK1 expression decelerated and LIMK1 knockdown accelerated actin
      retrograde flow. In the extending lamellipodia of neuregulin-stimulated MCF-7
      cells, LIMK1 knockdown accelerated both the rate of actin polymerization and the
      rate of actin retrograde flow, but the accelerating effect on retrograde flow was
      greater than the effect on polymerization, thus resulting in a decreased rate of
      lamellipodium extension. These results indicate that LIMK1 has a dual role in
      regulating lamellipodium extension by decelerating actin retrograde flow and
      polymerization, and in MCF-7 cells endogenous LIMK1 contributes to lamellipodium
      extension by decelerating actin retrograde flow more effectively than
      decelerating actin polymerization.

PMID- 21868384
TI  - The inhibitory effect of phospholemman on the sodium pump requires its
      palmitoylation.
AB  - Phospholemman (PLM), the principal sarcolemmal substrate for protein kinases A
      and C in the heart, regulates the cardiac sodium pump. We investigated post
      translational modifications of PLM additional to phosphorylation in adult rat
      ventricular myocytes (ARVM). LC-MS/MS of tryptically digested PLM
      immunoprecipitated from ARVM identified cysteine 40 as palmitoylated in some
      peptides, but no information was obtained regarding the palmitoylation status of
      cysteine 42. PLM palmitoylation was confirmed by immunoprecipitating PLM from
      ARVM loaded with [(3)H]palmitic acid and immunoblotting following streptavidin
      affinity purification from ARVM lysates subjected to fatty acyl biotin exchange.
      Mutagenesis identified both Cys-40 and Cys-42 of PLM as palmitoylated.
      Phosphorylation of PLM at serine 68 by PKA in ARVM or transiently transfected HEK
      cells increased its palmitoylation, but PKA activation did not increase the
      palmitoylation of S68A PLM-YFP in HEK cells. Wild type and unpalmitoylatable PLM
      YFP were all correctly targeted to the cell surface membrane, but the half-life
      of unpalmitoylatable PLM was reduced compared with wild type. In cells stably
      expressing inducible PLM, PLM expression inhibited the sodium pump, but PLM did
      not inhibit the sodium pump when palmitoylation was inhibited. Hence,
      palmitoylation of PLM controls its turnover, and palmitoylated PLM inhibits the
      sodium pump. Surprisingly, phosphorylation of PLM enhances its palmitoylation,
      probably through the enhanced mobility of the phosphorylated intracellular domain
      increasing the accessibility of cysteines for the palmitoylating enzyme, with
      interesting theoretical implications. All FXYD proteins have conserved
      intracellular cysteines, so FXYD protein palmitoylation may be a universal means
      to regulate the sodium pump.

PMID- 21868385
TI  - miR-155 inhibits expression of the MEF2A protein to repress skeletal muscle
      differentiation.
AB  - microRNAs (miRNAs) are 21-23-nucleotide non-coding RNAs. It has become more and
      more evident that this class of small RNAs plays critical roles in the regulation
      of gene expression at the post-transcriptional level. MEF2A is a member of the
      MEF2 (myogenic enhancer factor 2) family of transcription factors. Prior report
      showed that the 3'-untranslated region (3'-UTR) of the Mef2A gene mediated its
      repression; however, the molecular mechanism underlying this intriguing
      observation was unknown. Here, we report that MEF2A is repressed by miRNAs. We
      identify miR-155 as one of the primary miRNAs that significantly represses the
      expression of MEF2A. We show that knockdown of the Mef2A gene by siRNA impairs
      myoblast differentiation. Similarly, overexpression of miR-155 leads to the
      repression of endogenous MEF2A expression and the inhibition of myoblast
      differentiation. Most importantly, reintroduction of MEF2A in miR-155
      overexpressed myoblasts was able to partially rescue the miR-155-induced myoblast
      differentiation defect. Our data therefore establish miR-155 as an important
      regulator of MEF2A expression and uncover its function in muscle gene expression
      and myogenic differentiation.

PMID- 21868386
TI  - Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave
      of Rac1 activation in the process of cell migration.
AB  - Immense previous efforts have elucidated the core machinery in cell migration,
      actin remodeling regulated by Rho family small GTPases including RhoA, Cdc42, and
      Rac1; however, the spatiotemporal regulation of these molecules remains largely
      unknown. Here, we report that EGF induces biphasic Rac1 activation in the process
      of cell migration, and UTKO1, a cell migration inhibitor, inhibits the second EGF
      induced wave of Rac1 activation but not the first wave. To address the regulation
      mechanism and role of the second wave of Rac1 activation, we identified 14-3
      3zeta as a target protein of UTKO1 and also showed that UTKO1 abrogated the
      binding of 14-3-3zeta to Tiam1 that was responsible for the second wave of Rac1
      activation, suggesting that the interaction of 14-3-3zeta with Tiam1 is involved
      in this event. To our knowledge, this is the first report to use a chemical
      genetic approach to demonstrate the mechanism of temporal activation of Rac1.

PMID- 21868387
TI  - Yeast ADP/ATP carrier isoform 2: conformational dynamics and role of the RRRMMM
      signature sequence methionines.
AB  - The mitochondrial ADP/ATP carrier, or Ancp, is a member of the mitochondrial
      carrier family responsible for exchanging ADP and ATP across the mitochondrial
      inner membrane. ADP/ATP transport involves Ancp switching between two
      conformational states. These can be analyzed using specific inhibitors,
      carboxyatractyloside (CATR) and bongkrekic acid (BA). The high resolution three
      dimensional structure of bovine Anc1p (bAnc1p), as a CATR-carrier complex, has
      been solved. However, because the structure of the BA-carrier complex has not yet
      been determined, the detailed mechanism of transport remains unknown. Recently,
      sample processing for hydrogen/deuterium exchange experiments coupled to mass
      spectrometry was improved, providing novel insights into bAnc1p conformational
      transitions due to inhibitor binding. In this work we performed both
      hydrogen/deuterium exchange-mass spectrometry experiments and genetic
      manipulations. Because these are very difficult to apply with bovine Anc1p, we
      used Saccharomyces cerevisiae Anc isoform 2 (ScAnc2p). Significant differences in
      solvent accessibility were observed throughout the amino acid sequence for
      ScAnc2p complexed to either CATR or BA. Interestingly, in detergent solution, the
      conformational dynamics of ScAnc2p were dissimilar to those of bAnc1p, in
      particular for the upper half of the cavity, toward the intermembrane space, and
      the m2 loop, which is thought to be easily accessible to the solvent from the
      matrix in bAnc1p. Our study then focused on the methionyl residues of the Ancp
      signature sequence, RRRMMM. All our results indicate that the methionine cluster
      is involved in the ADP/ATP transport mechanism and confirm that the Ancp cavity
      is a highly dynamic structure.

PMID- 21868388
TI  - Evidence of the proximity of ATP synthase subunits 6 (a) in the inner
      mitochondrial membrane and in the supramolecular forms of Saccharomyces
      cerevisiae ATP synthase.
AB  - The involvement of subunit 6 (a) in the interface between yeast ATP synthase
      monomers has been highlighted. Based on the formation of a disulfide bond and
      using the unique cysteine 23 as target, we show that two subunits 6 are close in
      the inner mitochondrial membrane and in the solubilized supramolecular forms of
      the yeast ATP synthase. In a null mutant devoid of supernumerary subunits e and g
      that are involved in the stabilization of ATP synthase dimers, ATP synthase
      monomers are close enough in the inner mitochondrial membrane to make a disulfide
      bridge between their subunits 6, and this proximity is maintained in detergent
      extract containing this enzyme. The cross-linking of cysteine 23 located in the N
      terminal part of the first transmembrane helix of subunit 6 suggests that this
      membrane-spanning segment is in contact with its counterpart belonging to the ATP
      synthase monomer that faces it and participates in the monomer-monomer interface.

PMID- 21868389
TI  - Enabling association of the GINS protein tetramer with the mini chromosome
      maintenance (Mcm)2-7 protein complex by phosphorylated Sld2 protein and single
      stranded origin DNA.
AB  - The Cdc45-Mcm2-7-GINS (CMG) complex is the replication fork helicase in
      eukaryotes. Synthetic lethal with Dpb11-1 (Sld2) is required for the initiation
      of DNA replication, and the S phase cyclin-dependent kinase (S-CDK)
      phosphorylates Sld2 in vivo. We purified components of the replication initiation
      machinery and studied their interactions in vitro. We found that unphosphorylated
      or CDK-phosphorylated Sld2 binds to the mini chromosome maintenance (Mcm)2-7
      complex with similar efficiency. Sld2 interaction with Mcm2-7 blocks the
      interaction between GINS and Mcm2-7. The interaction between CDK-phosphorylated
      Sld2 and Mcm2-7 is substantially inhibited by origin single-stranded DNA (ssDNA).
      Furthermore, origin ssDNA allows GINS to bind to Mcm2-7 in the presence of CDK
      phosphorylated Sld2. However, unphosphorylated Sld2 blocks the interaction
      between GINS and Mcm2-7 even in the presence of origin ssDNA. We identified a
      mutant of Sld2 that does not bind to DNA. When this mutant is expressed in yeast
      cells, cell growth is severely inhibited with very slow progression into S phase.
      We propose a model wherein Sld2 blocks the interaction between GINS and Mcm2-7 in
      vivo. Once origin ssDNA is extruded from the Mcm2-7 ring and CDK phosphorylates
      Sld2, the origin ssDNA binds to CDK-phosphorylated Sld2. This event may allow the
      interaction between GINS and Mcm2-7 in vivo. Thus, CDK phosphorylation of Sld2
      may be important to release Sld2 from Mcm2-7, thereby allowing GINS to bind Mcm2
      7. Furthermore, origin ssDNA may stimulate the formation of the CMG complex by
      alleviating inhibitory interactions between Sld2 with Mcm2-7.

PMID- 21868390
TI  - Changes in regional and temporal patterns of activity associated with aging
      during the performance of a lexical set-shifting task.
AB  - Some older individuals seem to use compensatory mechanisms to maintain high-level
      performance when submitted to cognitive tasks. However, whether and how these
      mechanisms affect fronto-striatal activity has never been explored. The purpose
      of this study was to investigate how aging affects brain patterns during the
      performance of a lexical analog of the Wisconsin Card Sorting Task, which has
      been shown to strongly depend on fronto-striatal activity. In the present study,
      both younger and older individuals revealed significant fronto-striatal loop
      activity associated with planning and execution of set-shifts, though age-related
      striatal activity reduction was observed. Most importantly, while the younger
      group showed the involvement of a "cognitive loop" during the receiving negative
      feedback period (which indicates that a set-shift will be required to perform the
      following trial) and the involvement of a "motor loop" during the matching after
      negative feedback period (when the set-shift must be performed), older
      participants showed significant activation of both loops during the matching
      after negative feedback period only. These findings are in agreement with the
      "load-shift" model postulated by Velanova et al. (Velanova K, Lustig C, Jacoby
      LL, Buckner RL. 2007. Evidence for frontally mediated controlled processing
      differences in older adults. Cereb Cortex. 17:1033-1046.) and indicate that the
      model is not limited to memory retrieval but also applies to executive processes
      relying on fronto-striatal regions.

PMID- 21868391
TI  - Consecutive virgin births in the new world boid snake, the Colombian rainbow Boa,
      Epicrates maurus.
AB  - Until recently, facultative automictic parthenogenesis within the squamate
      reptiles exhibiting ZZ:ZW genetic sex determination has resulted in single
      reproductive events producing male (ZZ) or female (ZW) offspring. With the recent
      discovery of viable parthenogenetically produced female (WW) Boa constrictors,
      the existence of further parthenogenetic events resulting in WW females was
      questioned. Here, we provide genetic evidence for consecutive virgin births by a
      female Colombian rainbow boa (Epicrates maurus), resulting in the production of
      WW females likely through terminal fusion automixis. Samples were screened at 22
      microsatellite loci with 12 amplifying unambiguous products. Of these, maternal
      heterozygosity was observed in 4, with the offspring differentially homozygous at
      each locus. This study documents the first record of parthenogenesis within the
      genus Epicrates, a second within the serpent lineage Boidae, and the third
      genetically confirmed case of consecutive virgin births of viable offspring
      within any vertebrate lineage. Unlike the recent record in Boa constrictors, the
      female described here was isolated from conspecifics from birth, demonstrating
      that males are not required to stimulate parthenogenetic reproduction in this
      species and possibly other Boas.

PMID- 21868392
TI  - The unforeseen impact of meeting abstracts on cancer research.

PMID- 21868393
TI  - Impairment of lon-induced protection against the accumulation of oxidized
      proteins in senescent wi-38 fibroblasts.
AB  - Oxidative damage to mitochondrial proteins is thought to contribute to the aging
      process, but the Lon protease normally degrades such proteins. In early-passage
      WI-38 human lung fibroblasts, Lon expression is rapidly induced during H(2)O(2)
      stress, which prevents the accumulation of oxidized proteins and protects cell
      viability. In contrast, middle passage cells exhibit only sluggish induction of
      Lon expression in oxidative stress, and oxidized proteins initially accumulate.
      Late-passage, or senescent, cells have low basal levels of Lon and high levels of
      accumulated oxidized proteins; in response to oxidative stress, they fail to
      induce Lon expression and exhibit continually increasing accumulation of oxidized
      proteins. Senescent cells separated into two populations, one exhibiting normal
      mitochondrial mass and a second displaying significant loss of mitochondria; both
      populations had diminished mitochondrial transmembrane potential. These senescent
      changes are similar to the effects of Lon silencing in young cells. We suggest
      that loss of Lon stress inducibility is part of a pattern of diminishing stress
      adaptability that predisposes cells to senescence.

PMID- 21868394
TI  - On metaphorical concentration: language and meaning in patient-physician
      relations.
AB  - Charles Taylor's retrieval of an expressivist understanding of persons, and of
      language as constitutive of meaning, contains promising insights for restoring
      moral connectedness between patients and physicians.

PMID- 21868396
TI  - Time for an eGFR equivalent in AKI recognition?

PMID- 21868395
TI  - Pharmacokinetics of sulfobutylether-beta-cyclodextrin (SBECD) in subjects on
      hemodialysis.
AB  - BACKGROUND: The disposition of sulfobutylether-beta-cyclodextrin (SBECD), the
      solubilizing excipient in intravenous (i.v.) voriconazole, was assessed in seven
      male subjects with end-stage renal disease on hemodialysis and six subjects with
      normal renal function. METHODS: All subjects received twice-daily i.v.
      voriconazole at the standard voriconazole dose [6 mg/kg (96 mg/kg SBECD) every 12
      h (Q12h) on Day 1 followed by 3 mg/kg (48 mg/kg SBECD) Q12h on Days 2-4, with a
      single i.v. dose on the morning of Day 5]. Subjects were sampled at selected pre
      dose trough times, at selected times after infusions and intensively on Day 3
      (non-dialysis) and Day 4 (dialysis with high-flux membranes). Compartmental
      analyses were performed by NONMEM. RESULTS: SBECD disposition was characterized
      by a two-compartment model. In renal failure, mean central (V(1)) and peripheral
      compartment volumes (V(2)) were 9.9 and 6.5 L, respectively. In normal subjects,
      V(1) and V(2) were 9.6 and 5.2 L, respectively; SBECD clearance (CL) was 130
      mL/min. CL in renal failure off-dialysis was 2.6 and 48 mL/min during dialysis;
      mean half-life decreased from 79 to 5 h during dialysis (normal subjects: 2.1 h).
      CONCLUSION: Hemodialysis can significantly reduce levels of SBECD in subjects
      with end-stage renal disease.

PMID- 21868397
TI  - VEGF regulates TRPC6 channels in podocytes.
AB  - BACKGROUND: Both, increased plasma concentrations of vascular endothelial growth
      factor (VEGF) and increased expression of transient receptor potential canonical
      type 6 (TRPC6) channels in podocytes have been associated with proteinuric kidney
      diseases. Now, we investigated the hypothesis that VEGF regulates TRPC6 in
      podocytes. METHODS: TRPC6 messenger RNA (mRNA) and TRPC6 protein expression were
      analyzed in cultured podocytes after administration of VEGF165 using quantitative
      real-time reverse transcription-polymerase chain reaction and immunoblotting,
      respectively. YFP-tagged TRPC6 in podocytes was analyzed using confocal laser
      scanning microscopy. TRPC6-associated calcium influx was measured
      fluorometrically. Both, immunofluorescence and immunohistochemistry were
      performed in renal tissue from patients with diabetes mellitus and controls.
      RESULTS: Administration of VEGF165 to podocytes significantly increased TRPC6
      mRNA expression and TRPC6 protein levels. The effects of VEGF165 were dose
      dependent and could be blocked by phosphoinositide-3-kinase inhibitors. In the
      presence of cycloheximide, an inhibitor of protein biosynthesis, we did not
      observe an effect of VEGF on TRPC6 protein levels, indicating the requirement of
      de novo protein synthesis. VEGF165 significantly increased TRPC6-mediated calcium
      influx in podocytes. Calcium influx was significantly lower in podocytes after
      gene knockdown using siRNA against TRPC6. Immunohistochemistry showed both
      increased TRPC6 channel protein and VEGF receptor type 2 (VEGFR-2) protein in
      podocytes from patients with diabetic nephropathy compared to control subjects.
      There was a significant association between VEGFR-2 mRNA and TRPC6 mRNA (n = 48;
      r(2) = 0.585; P < 0.0001) in human renal cortex. CONCLUSION: VEGF regulates TRPC6
      in podocytes.

PMID- 21868398
TI  - Allometry of root branching and its relationship to root morphological and
      functional traits in three range grasses.
AB  - The study of proportional relationships between size, shape, and function of part
      of or the whole organism is traditionally known as allometry. Examination of
      correlative changes in the size of interbranch distances (IBDs) at different root
      orders may help to identify root branching rules. Root morphological and
      functional characteristics in three range grasses {bluebunch wheatgrass
      [Pseudoroegneria spicata (Pursh) Love], crested wheatgrass [Agropyron desertorum
      (Fisch. ex Link) Schult.*A. cristatum (L.) Gaert.], and cheatgrass (Bromus
      tectorum L.)} were examined in response to a soil nutrient gradient. Interbranch
      distances along the main root axis and the first-order laterals as well as other
      morphological and allocation root traits were determined. A model of nutrient
      diffusivity parameterized with root length and root diameter for the three
      grasses was used to estimate root functional properties (exploitation efficiency
      and exploitation potential). The results showed a significant negative allometric
      relationship between the main root axis and first-order lateral IBD (P <= 0.05),
      but only for bluebunch wheatgrass. The main root axis IBD was positively related
      to the number and length of roots, estimated exploitation efficiency of second
      order roots, and specific root length, and was negatively related to estimated
      exploitation potential of first-order roots. Conversely, crested wheatgrass and
      cheatgrass, which rely mainly on root proliferation responses, exhibited fewer
      allometric relationships. Thus, the results suggested that species such as
      bluebunch wheatgrass, which display slow root growth and architectural root
      plasticity rather than opportunistic root proliferation and rapid growth, exhibit
      correlative allometry between the main axis IBD and morphological, allocation,
      and functional traits of roots.

PMID- 21868399
TI  - Functional effect of grapevine 1-deoxy-D-xylulose 5-phosphate synthase
      substitution K284N on Muscat flavour formation.
AB  - Grape berries of Muscat cultivars (Vitis vinifera L.) contain high levels of
      monoterpenols and exhibit a distinct aroma related to this composition of
      volatiles. A structural gene of the plastidial methyl-erythritol-phosphate (MEP)
      pathway, 1-deoxy-D-xylulose 5-phosphate synthase (VvDXS), was recently suggested
      as a candidate gene for this trait, having been co-localized with a major
      quantitative trait locus for linalool, nerol, and geraniol concentrations in
      berries. In addition, a structured association study discovered a putative causal
      single nucleotide polymorphism (SNP) responsible for the substitution of a lysine
      with an asparagine at position 284 of the VvDXS protein, and this SNP was
      significantly associated with Muscat-flavoured varieties. The significance of
      this nucleotide difference was investigated by comparing the monoterpene profiles
      with the expression of VvDXS alleles throughout berry development in Moscato
      Bianco, a cultivar heterozygous for the SNP mutation. Although correlation was
      detected between the VvDXS transcript profile and the accumulation of free
      monoterpenol odorants, the modulation of VvDXS expression during berry
      development appears to be independent of nucleotide variation in the coding
      sequence. In order to assess how the non-synonymous mutation may enhance Muscat
      flavour, an in vitro characterization of enzyme isoforms was performed followed
      by in vivo overexpression of each VvDXS allele in tobacco. The results showed
      that the amino acid non-neutral substitution influences the enzyme kinetics by
      increasing the catalytic efficiency and also dramatically affects monoterpene
      levels in transgenic lines. These findings confirm a functional effect of the
      VvDXS gene polymorphism and may pave the way for metabolic engineering of
      terpenoid contents in grapevine.

PMID- 21868400
TI  - Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization:
      prospective cohort study.
AB  - BACKGROUND: The influence of thrombophilia on fertility and on IVF outcome is
      very controversial. The objectives of this study were: (i) to compare the
      prevalence of Factor V Leiden (FVL) and prothrombin gene G20210A mutation (PGM)
      in women undergoing IVF to women with spontaneous pregnancy; (ii) to compare the
      IVF outcomes and the risk of complications in FVL and PGM carrier to non-carrier
      women. METHODS: From March 2005 to December 2009, a total of 510 women requiring
      IVF were recruited in a prospective cohort study. A separate population of 490
      nulliparous women who conceived naturally was also evaluated as fertile controls.
      All women were tested for the presence of FVL and PGM. RESULTS: The prevalence of
      thrombophilic mutations was the same among women requiring IVF (6.9%) and women
      with spontaneous pregnancy (6.9%). A total of 480 patients underwent 1105 IVF
      cycles. There were 30 women carriers (86 IVF cycles) and 450 non-carriers for
      thrombophilic mutations (1019 IVF cycles). No significant differences in the mean
      number of oocytes retrieved and the number of good quality embryos transferred
      were found between the mutation carrier and non-mutation carrier women; likewise
      the reproductive outcome and the IVF complications were not statistically
      different between the two groups. The cumulative live birth rate after six IVF
      cycles was similar in the mutation carrier and non-mutation carrier women. For
      the mutation carrier women, the optimistic estimate of cumulative live birth rate
      after six IVF cycles was 60.8% and the conservative estimate was 50.0%.
      Corresponding rates for the non-mutation carrier women were 56.8 and 36.2%,
      respectively. CONCLUSIONS: The results of this study suggest that FVL and PGM
      presence in asymptomatic women and in the absence of other risk factors do not
      influence IVF outcome, or represent risk factors for ovarian hyperstimulation
      syndrome (OHSS), or favour thrombosis after IVF. Screening for FVL and PGM does
      not appear to be justified to identify the patients at the risk for IVF failure,
      and/or for OHSS, and/or for thrombotic complications.

PMID- 21868401
TI  - Ovarian surgery for bilateral endometriomas influences age at menopause.
AB  - BACKGROUND: Questions remain as to whether surgical excision of ovarian
      endometriomas might cause damage to ovarian function. To test the hypothesis that
      ovarian surgery for endometrioma compromises ovarian function and accelerates
      ovarian failure. METHODS: In a tertiary university Clinic, longitudinal
      prospective cohort study. Patients who underwent laparoscopy for endometriosis
      between March 1993 and November 2007 were assessed for inclusion in the study. A
      prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution
      of menstrual pattern, symptoms and reproductive outcomes were investigated.
      RESULTS: From over the 14-year period, 302 patients were included in the study.
      The mean age (+/-SD) of patients was 32.6 +/- 5.6 years; the median duration of
      follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women
      (14.3%) at a mean age of 45.3 +/- 4.3 years (range 32-52 years). Women previously
      submitted to bilateral cystectomy were younger at menopause than those with
      monolateral endometrioma (42.1 +/- 5.1 years versus 47.1 +/- 3.5 years, P =
      0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%)
      menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The
      relationship between the preoperative ovarian endometriomas total diameter and
      menopausal age was significant in case of surgery for bilateral endometriomas
      (R(2) = 0.754, P = 0.002). CONCLUSIONS: Patients who had been operated on for
      bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at
      the time of surgery seems related to cyst diameter. In the case of unilateral
      ovarian endometrioma, the contralateral intact ovary might adequately compensate.

PMID- 21868403
TI  - Light acclimation potential and carry-over effects vary among three evergreen
      tree species with contrasting patterns of leaf emergence and maturation.
AB  - We compared light acclimation potential among three evergreen broadleaved species
      with contrasting patterns of shoot elongation, leaf emergence and leaf
      maturation. Understory saplings were transferred to a high-light environment
      before bud break, grown for 13 months, and then transferred back to the
      understory to observe subsequent carry-over effects. Acclimation potential was
      highest and sapling mortality was lowest for Cinnamomum japonicum Sieb. ex Nakai.
      Indeterminate growth and successive leaf emergence allowed this species to
      acclimate to both high and low light by adjusting leaf production as well as leaf
      properties. Sapling mortality occurred after both transfers for Camellia japonica
      L., which also has indeterminate growth and successive leaf emergence. In this
      species, carry-over effects were observed at the individual level, but leaf-level
      acclimation potential was high. Acclimation potential was lowest and sapling
      mortality occurred soon after the transfer to high light for Quercus glauca
      Thunb. ex Murray. Determinate growth and flush-type leaf emergence resulted in
      significant carry-over effects in this species. Indeterminate growth and
      successive leaf emergence increase whole-plant acclimation potential by extending
      the period of growth and architectural development during the growing season.
      Similarly, we inferred that delayed leaf maturation, observed in many evergreen
      species, increases the acclimation potential of current-year leaves by extending
      the period of leaf development. In evergreen species, the acclimation potential
      of preexisting leaves determines the role that leaf turnover plays in whole-plant
      light acclimation, resulting in diverse strategies for light acclimation among
      species, as observed in this study.

PMID- 21868402
TI  - Prenatal environmental risk factors for genital malformations in a population of
      1442 French male newborns: a nested case-control study.
AB  - BACKGROUND: Over the past decades, an increasing trend in male external genital
      malformations such as cryptorchidism and hypospadias has led to the suspicion
      that environmental chemicals are detrimental to male fetal sexual development.
      Several environmental pollutants, including organochlorine pesticides,
      polychlorinated biphenyls, bisphenol A, phthalates, dioxins and furans have
      estrogenic and anti-androgenic activity and are thus considered as endocrine
      disrupting chemicals (EDCs). Since male sex differentiation is critically
      dependent on the normal production and action of androgens during fetal life,
      EDCs may be able to alter normal male sex differentiation. OBJECTIVE: The
      objective of this study was to determine the incidence of external genital
      malformations in a population of full-term newborn males in southern France. We
      also performed a case-control study to identify the risk factors for male
      external genital malformations, with a focus on parental occupational exposure to
      EDCs. METHODS: Over a 16-month period, 1615 full-term newborn males with a birth
      weight above 2500 g were registered on a level-1 maternity ward, and the same
      pediatrician systematically examined 1442 of them (89%) for cryptorchidism,
      hypospadias and micropenis. For every male newborn with genital malformation, we
      enrolled nearly two males matched for age, parity and term. All parents of the
      case and control newborns were interviewed about pregnancy aspects, personal
      characteristics, lifestyle and their occupational exposure to EDCs using a
      detailed questionnaire. RESULTS We report 39 cases of genital malformation
      (2.70%), with 18 cases of cryptorchidism (1.25%), 14 of hypospadias (0.97%), 5 of
      micropenis (0.35%) and 2 of 46,XY disorders of sexual differentiation (DSD;
      0.14%). We observed a significant relationship between newborn cryptorchidism,
      hypospadias or micropenis and parental occupational exposure to pesticides [odds
      ratio (OR) = 4.41; 95% confidence interval (95% CI), 1.21-16.00]. Familial
      clustering for male external genital malformations (OR = 7.25; 95% CI, 0.70
      74.30) and medications taken by mothers during pregnancy (OR = 5.87; 95% CI, 0.93
      37.00) were associated with the risk of cryptorchidism, hypospadias and
      micropenis, although the association was not statistically significant.
      CONCLUSIONS: Although the causes of male genital malformation are multifactorial,
      our data support the hypothesis that prenatal contamination by pesticides may be
      a potential risk factor for newborn male external genital malformation and it
      should thus be routinely investigated in all undervirilized newborn males.

PMID- 21868404
TI  - Visual impairment in children in middle- and lower-income countries.
AB  - Reducing visual impairment and blindness in children in resource-poor countries
      is one of the key components of the major global prevention of blindness
      initiative, VISION 2020 the Right to Sight. Although visual impairment and
      blindness among children is much less common than among adults, the potential
      lifespan of a child means that the lifelong impact of such impairment is very
      large. Over 10 years ago, it was estimated that, globally, 1.4 million children
      were blind. Much has changed in the past 10-20 years and there is a need to
      reassess both the magnitude and causes of global childhood blindness and visual
      impairment. While the widespread implementation of vitamin A supplementation and
      measles immunisation programmes have led to a reduction in vitamin A deficiency
      related blindness in many poor countries, retinopathy of prematurity is now
      undergoing a third wave of endemicity, particularly in newly industrialising
      countries in Latin America and Asia. Childhood cataract is better recognised as
      an important potentially avoidable problem, as is paediatric glaucoma and
      refractive error in some populations. Trained paediatric ophthalmologists,
      although still too few, are growing in number in poor countries. A programmatic
      approach with a multidisciplinary team is essential to reducing childhood
      blindness. The elements of such programmes and the need for planning are
      discussed.

PMID- 21868405
TI  - Systematic review of studies comparing combined treatment with paracetamol and
      ibuprofen, with either drug alone.
AB  - OBJECTIVE: To evaluate the evidence surrounding the use of combinations of
      paracetamol and ibuprofen in the treatment of fever. DESIGN: Systematic narrative
      review of randomised controlled trials using the UK Economic and Social Research
      Council guidance on the conduct of narrative synthesis. SETTING: Inpatient,
      outpatient and home care. PATIENTS: Children with fever. MAIN OUTCOME MEASURES:
      The effect of combination treatments of paracetamol and ibuprofen on fever and
      comfort, and identification of side effects. RESULTS: Seven studies were
      identified, six of which provided useful data for the evaluation of the effect of
      treatment on temperature. Overall these studies showed limited benefit from the
      combined treatment until around 4 h, after which there was a statistically but
      only marginally clinically significant benefit. Two studies contained data
      directly relating to comfort; these suggest a marginal benefit from the combined
      treatment, but the clinical significance of this was limited. There was no
      evidence of greater side effects or toxicities associated with the combined
      treatment. However, it is important to note that these studies were small, short
      term, and not conducted in the normal setting in which these treatments are
      given. CONCLUSIONS: There is little evidence of any benefit or harm from the
      combined treatment compared with the use of each drug alone. In the absence of
      such benefit, there is little to recommend the unnecessary use of
      polypharmaceutical methods to treat a symptom that does not require treatment,
      when effective monotherapies exist.

PMID- 21868407
TI  - Elusive but not hypothetical: axillary meristems in Wollemia nobilis.
AB  - BACKGROUND: The branches of Wollemia nobilis are unbranched; however, it has been
      noted that new branches can form from the distal end of damaged ones, and
      branches can grow from axillary structures once a terminal strobilus has fallen.
      Tomlinson and Huggett (2011, Annals of Botany 107: 909-916) have recently
      investigated the formation of these reiterative branches and stated in the title
      of their paper that 'Partial shoot reiteration in Wollemia nobilis
      (Araucariaceae) does not arise from "axillary meristems"'. They go on to state
      'Further research may reveal the presence of these elusive, but still only
      hypothetical, axillary meristems'. RESPONSE: In this Viewpoint, I argue that
      Tomlinson and Huggett do not refer to previously published information that
      indicates that axillary meristems are present in Wollemia nobilis branch leaf
      axils, and that their anatomical methods were probably not optimal for locating
      and examining these minute structures. Thus, whilst I would agree that the
      axillary meristems in branch leaf axils of Wollemia nobilis are elusive, I
      contend that they are not hypothetical.

PMID- 21868406
TI  - Interactive effects of plant-available soil silicon and herbivory on competition
      between two grass species.
AB  - BACKGROUND AND AIMS: The herbivore defence system of true grasses (Poaceae) is
      predominantly based on silicon that is taken up from the soil and deposited in
      the leaves in the form of abrasive phytoliths. Silicon uptake mechanisms can be
      both passive and active, with the latter suggesting that there is an energetic
      cost to silicon uptake. This study assessed the effects of plant-available soil
      silicon and herbivory on the competitive interactions between the grasses Poa
      annua, a species that has previously been reported to accumulate only small
      amounts of silicon, and Lolium perenne, a high silicon accumulator. METHODS:
      Plants were grown in mono- and mixed cultures under greenhouse conditions. Plant
      available soil silicon levels were manipulated by adding silicon to the soil in
      the form of sodium silicate. Subsets of mixed culture pots were exposed to above
      ground herbivory by desert locusts (Schistocerca gregaria). KEY RESULTS: In the
      absence of herbivory, silicon addition increased biomass of P. annua but
      decreased biomass of L. perenne. Silicon addition increased foliar silicon
      concentrations of both grass species >4-fold. Under low soil-silicon availability
      the herbivores removed more leaf biomass from L. perenne than from P. annua,
      whereas under high silicon availability the reverse was true. Consequently,
      herbivory shifted the competitive balance between the two grass species, with the
      outcome depending on the availability of soil silicon. CONCLUSIONS: It is
      concluded that a complex interplay between herbivore abundance, growth-defence
      trade-offs and the availability of soil silicon in the grasses' local environment
      affects the outcome of inter-specific competition, and so has the potential to
      impact on plant community structure.

PMID- 21868408
TI  - Aorta to right ventricular tunnel: a rare cause of holodiastolic flow reversal in
      aorta in an infant.

PMID- 21868409
TI  - Mitral regurgitation and cardiac resynchronization therapy: how long and what
      should we expect?

PMID- 21868410
TI  - Possible refinement of clinical thromboembolism assessment in patients with
      atrial fibrillation using echocardiographic parameters.
AB  - AIM: Some transoesophageal echocardiogram (TEE) findings are associated with an
      increased risk of stroke in patients with atrial fibrillation (AF). This study
      was designed to evaluate and compare the accuracy of CHADS(2) and CHA(2)DS(2)
      VASc in the prediction of these findings and test the additive value of
      transthoracic echocardiogram (TTE)-derived parameters as a possible refinement
      for these classifications. METHODS AND RESULTS: Cross-sectional study of 405
      consecutive patients who underwent TTE and TEE evaluation during AF. Stroke risk
      assessment was performed using the CHADS(2) and CHA(2)DS(2)-VASc scores, alone
      and alongside with the addition of two TTE-derived parameters (left atrium area
      and left ventricle global systolic function). Comparisons regarding the presence
      of left atrial appendage thrombi (LAA T), dense spontaneous echo contrast (SEC),
      and left atrial appendage (LAA) low flow velocities (LFV) were performed using
      receiver operating characteristic curves. In low-risk patients, as assessed
      through the CHA(2)DS(2)-VASc score and CHADS(2) and CHA(2)DS(2)-VASc scores plus
      echo parameters, no high-risk features were found on TEE. In subjects classified
      as low risk using CHADS(2), this figure rose to 10%. No significant differences
      were found between CHADS(2) and CHA(2)DS(2)-VASc in the prediction of LAA T,
      dense SEC, and LAA LFV. The addition of TTE-derived parameters to the previous
      clinical-risk scores resulted in improved prediction of the TEE endpoints.
      CONCLUSION: These findings suggest that the use of TTE-derived parameters may be
      a valuable way of refining the available clinical risk schemes for the detection
      of surrogate markers of stroke. Follow-up studies using clinical endpoints will
      be necessary to confirm this hypothesis.

PMID- 21868411
TI  - A new integrated approach to improve left ventricular electromechanical
      activation during right ventricular septal pacing.
AB  - AIMS: The deleterious effects of apical right ventricular pacing has fostered the
      utilization of alternative pacing sites. Although right ventricular septal (RVS)
      sites are commonly used, the results have been controversial because of poor
      standardization of lead position by fluoroscopy. This study investigated the
      utility of a new RVS pacing technique based on the combination of fluoroscopy
      (F), and electrophysiological mapping (F + EP). Left ventricular (LV)
      electromechanical activation was determined in patients undergoing RVS pacing and
      the results of the F + EP approach were compared with those derived from standard
      F alone. METHODS AND RESULTS: Between December 2008 and November 2010 we enrolled
      156 consecutive patients undergoing permanent RVS pacing. The standard F approach
      was used in 93 patients and the F + EP technique was applied to 63 patients.
      Electromechanical activation was assessed by: (i) electromechanical latency (EML)
      interval measured from the QRS onset to the mechanical activation of the basal LV
      and (ii) intra-LV dyssynchrony measured as the interval from the earliest to the
      latest LV basal motion. Intra-LV dyssynchrony was found in 46.2% patients in the
      F group compared with 15.9% in the group F + EP (P < 0.001). The F group
      demonstrated a significantly higher degree of intra-LV dyssynchrony than F + EP
      group (43.9 +/- 24.3 vs. 26.5 +/- 15.4 ms; P < 0.001). The F group exhibited a
      significantly higher EML duration compared with the F + EP group (215.8 +/- 25.3
      vs. 195.1 +/- 17.4 ms; P < 0.001). CONCLUSION: During RVS pacing, the F + EP
      approach provides a more physiological LV activation than the standard F
      technique. The prognostic significance of these short-term findings needs to be
      correlated with long-term data.

PMID- 21868412
TI  - Stereotactic brachytherapy of low-grade cerebral glioma after tumor resection.
AB  - The purpose of this study was to assess the impact of stereotactic brachytherapy
      (SBT) on survival time and outcome when applied after resection of low-grade
      glioma (LGG) of World Health Organization grade II. From January 1982 through
      December 2006 we treated 1024 patients who had glioma with stereotactic
      implantation of iodine-125 seeds and SBT in accordance with a prospective
      protocol. For the present analysis, we selected 95 of 277 patients with LGG, in
      whom SBT was applied to treat progressive (43 patients) or recurrent (52
      patients) tumor after resection. At 24 months after seed implantation, the tumor
      response rate was 35.9%, and the tumor control rate was 97.3%. The median
      progression-free-survival (PFS) duration after SBT was 52.7 +/- 7.1 months. Five
      year and 10-year PFS probabilities were 43.4% and 10.7%, respectively. Malignant
      tumor transformation, the diagnosis "astrocytoma," and tumor volume >20 mL were
      significantly associated with reduced PFS. Tumor progression or relapse after SBT
      (53 of 95 patients) was treated with tumor resection, a second SBT, chemotherapy,
      and/or radiotherapy. The median overall survival duration (from the first
      diagnosis of LGG until the patient's last contact) was 245.0 +/- 4.9 months.
      Patients still under observation after seed implantation had a median follow-up
      time of 156.4 +/- 55.7 months. Perioperative transient morbidity was 1.1%, and
      the frequency of permanent morbidity caused by SBT was 3.3%. In conclusion, SBT
      of recurrent or progressive LGG after resection located in functionally critical
      brain areas has high local efficacy and comparably low morbidity. Referred to
      individually adopted glioma treatment concepts SBT provides a reasonably long
      PFS, thus improving overall survival. In selected patients, SBT can lead to
      delays in the application of chemotherapy and/or radiotherapy.

PMID- 21868413
TI  - Methicillin-susceptible Staphylococcus aureus ST398-t571 harbouring the macrolide
      lincosamide-streptogramin B resistance gene erm(T) in Belgian hospitals.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin
      susceptible S. aureus (MSSA), collected from 109 Belgian acute-care hospitals
      during a national survey in 2008, were investigated for macrolide-lincosamide
      (ML) resistance with particular emphasis on the analysis of erm(T)-carrying
      isolates. METHODS: In total, 314 MRSA and 212 MSSA were collected and
      characterized by spa typing. The SCCmec type of MRSA was determined. Resistance
      to ML antibiotics was detected by agar dilution and resistant strains were
      screened by PCR for erm(A), erm(C) and msr(A). Five ML-resistant MSSA isolates,
      negative by PCR for the aforementioned genes, were further characterized.
      RESULTS: Half of all MRSA isolates (n = 157; 50.0%) were resistant to
      erythromycin and harboured the gene erm(A) (n = 112), erm(C) (n = 41), erm(A) +
      erm(C) (n = 3) or msr(A) (n = 1). The erm(A) gene was mainly present in MRSA spa
      CC002-ST5-SCCmec II and spa-CC008-ST8-SCCmec IV (where CC stands for clonal
      complex and ST stands for sequence type); the distribution of erm(C) was more
      diverse. Thirty-five of the 40 erythromycin-resistant MSSA (18.9%) carried the
      gene erm(A) (n = 17), erm(C) (n = 9) or msr(A) (n = 9). The remaining five MSSA
      were ST398-t571 isolates, which exhibited closely related ApaI PFGE patterns,
      harboured the gene erm(T) in the chromosomal DNA and did not exhibit additional
      resistances. These isolates were from severe infections in patients, of whom four
      had no contact and one had only indirect contact with livestock via a family
      member working in animal husbandry. CONCLUSIONS: The ML-streptogramin B
      ('MLS(B)') resistance genes erm(A) or erm(C) were detected in the majority of ML
      resistant MRSA and MSSA isolates. The erm(T) gene was identified in MSSA ST398
      isolates from five independent patients who lacked direct contact with livestock.

PMID- 21868415
TI  - Paradoxical decrease in serum high-density lipoprotein cholesterol with
      Tredaptive(r) (m/r nicotinic acid 1 g and laropiprant 20 mg).

PMID- 21868414
TI  - The N-acetyl-binding pocket of N-acetylglucosaminyltransferases also accommodates
      a sugar analog with a chemical handle at C2.
AB  - In recent years, sugars with a unique chemical handle have been used to detect
      and elucidate the function of glycoconjugates. Such chemical handles have
      generally been part of an N-acetyl moiety of a sugar. We have previously
      developed several applications using the single mutant Y289L-beta1,4
      galactosyltransferase I (Y289L-beta4Gal-T1) and the wild-type polypeptide-alpha
      GalNAc-T enzymes with UDP-C2-keto-Gal. Here, we describe for the first time that
      the GlcNAc-transferring enzymes-R228K-Y289L-beta4Gal-T1 mutant enzyme, the wild
      type human beta1,3-N-acetylglucosaminyltransferase-2 and human Maniac Fringe-can
      also transfer the GlcNAc analog C2-keto-Glc molecule from UDP-C2-keto-Glc to
      their respective acceptor substrates. Although the R228K-Y289L-beta4Gal-T1 mutant
      enzyme transfers the donor sugar substrate GlcNAc or its analog C2-keto-Glc only
      to its natural acceptor substrate, GlcNAc, it does not transfer to its analog C2
      keto-Glc. Thus, these observations suggest that the GlcNAc-transferring
      glycosyltransferases can generally accommodate a chemical handle in the N-acetyl
      binding cavity of the donor sugar substrate, but not in the N-acetyl-binding
      cavity of the acceptor sugar.

PMID- 21868416
TI  - Hair testing is taking root.
AB  - An increasing number of toxicology laboratories are choosing to expand the
      services they offer to include hair testing in response to customer demands. Hair
      provides the toxicologist with many advantages over conventional matrices in that
      it is easy to collect, is a robust and stable matrix that does not require
      refrigeration, and most importantly, provides a historical profile of an
      individual's exposure to drugs or analytes of interest. The establishment of hair
      as a complementary technique in forensic toxicology is a direct result of the
      success of the matrix in medicolegal cases and the wide range of applications.
      However, before introducing hair testing, laboratories must consider what
      additional requirements they will need that extend beyond simply adapting
      methodologies already validated for blood or urine. Hair presents many challenges
      with respect to the lack of available quality control materials, extensive sample
      handling protocols and low drug concentrations requiring greater instrument
      sensitivity. Unfortunately, a common pitfall involves over-interpretation of the
      findings and must be avoided.

PMID- 21868418
TI  - Full-thickness laparoendoscopic excision in the stomach: the FLEx technique.
AB  - BACKGROUND: The authors describe the initial validation of a novel full-thickness
      laparoendoscopic excision (FLEx) technique for the stomach. METHODS: The
      technique was studied in seven 50-kg pigs. Secure full-thickness excision was
      ensured by inversion excision target with a 1-cm circumferential margin using
      laparoendoscopically placed brace bars passed intraluminally from the outside of
      the stomach, laparoscopic oversewing of the site of inversion, and endoscopic
      full-thickness excision using a dual scope approach. Pigs were sacrificed either
      immediately (n = 3) or between 7 and 10 days after surgery (n = 4). RESULTS: The
      procedure achieved uncomplicated full-thickness excision in every case. Median
      procedure duration was 227 minutes (range = 210-245 minutes). Median specimen
      diameter was 5.5 cm (range = 2.5-8 cm). Investigative autopsy confirmed technical
      sufficiency in all animals. Median site bursting pressure was 130 mm Hg (range =
      120-160 mm Hg). CONCLUSIONS: The FLEx technique proved useful for excision of
      small localized lesions of the stomach in this animal study.

PMID- 21868417
TI  - Closed incision management with negative pressure wound therapy (CIM):
      biomechanics.
AB  - A novel closed incision management with negative pressure wound therapy (CIM) has
      been developed for convenient use with closed incisions that has the potential to
      be beneficial for patients at risk for postoperative complications. Incisions are
      typically under lateral tension. This study explored the biomechanical mechanisms
      by which integrity of the incisional closure is enhanced by CIM. CIM was
      hypothesized to affect local stresses around closed incisions in a beneficial
      manner. Finite element analyses (FEA) indicated that application of CIM decreased
      the lateral stresses ~50% around the incision and changed the direction of the
      stresses to a distribution that is typical of intact tissue. Bench evaluations
      corroborated findings that CIM significantly increased the force required to
      disrupt the closed incision by ~50% as compared with closure alone. In
      conclusion, using 2 FEAs and bench modeling, CIM was shown to reduce and
      normalize tissue stresses and bolster appositional forces at the incision.

PMID- 21868419
TI  - Survey on surgical instrument handle design: ergonomics and acceptance.
AB  - Minimally invasive surgical approaches have revolutionized surgical care and
      considerably improved surgical outcomes. The instrumentation has changed
      significantly from open to laparoscopic and robotic surgery with various
      usability and ergonomics qualities. To establish guidelines for future designing
      of surgical instruments, this study assesses the effects of current surgical
      approaches and instruments on the surgeon. Furthermore, an analysis of surgeons'
      preferences with respect to instrument handles was performed to identify the main
      acceptance criteria. In all, 49 surgeons (24 with robotic surgery experience, 25
      without) completed the survey about physical discomfort and working conditions.
      The respondents evaluated comfort, intuitiveness, precision, and stability of 7
      instrument handles. Robotic surgery procedures generally take a longer time than
      conventional procedures but result in less back, shoulder, and wrist pain; 28% of
      surgeons complained about finger and neck pain during robotic surgery. Three
      handles (conventional needle holder, da Vinci wrist, and joystick-like handle)
      received significantly higher scores for most of the proposed criteria. The
      handle preference is best explained by a regression model related only to comfort
      and precision (R(2) = 0.91) and is significantly affected by the surgeon's
      background (P < .001). Although robotic surgery seems to alleviate physical
      discomfort during and after surgery, the results of this study show that there is
      room for improvement in the sitting posture and in the ergonomics of the handles.
      Comfort and precision have been found to be the most important aspects for the
      surgeon's choice of an instrument handle. Furthermore, surgeons' professional
      background should be considered when designing novel surgical instruments.

PMID- 21868420
TI  - Surgical videos for accident analysis, performance improvement, and complication
      prevention: time for a surgical black box?
AB  - Conventional audit of surgical records through review of surgical results
      provides useful knowledge but hardly helps identify the technical reasons lying
      behind specific outcomes or complications. Surgical teams not only need to know
      that a complication might happen but also how and when it is most likely to
      happen. Functional awareness is therefore needed to prevent complications, know
      how to deal with them, and improve overall surgical performance. The authors wish
      to argue that the systematic recording and reviewing of surgical videos, a
      "surgical black box," might improve surgical care, help prevent complications,
      and allow accident analysis. A possible strategy to test this hypothesis is
      presented and discussed. Recording and reviewing surgical interventions, apart
      from helping us achieve functional awareness and increasing the safety profile of
      our performance, allows us also to effectively share our experience with
      colleagues. The authors believe that those potential implications make this
      hypothesis worth testing.

PMID- 21868421
TI  - Single-incision laparoscopic reversal of Hartmann procedure via the colostomy
      site only: first report.
AB  - BACKGROUND: Transumbilical single-incision laparoscopic surgery (SILS) provides
      an alternative to traditional multiport laparoscopic surgery. The technique may
      also avoid some of the difficulties surrounding laparoscopic Hartmann reversal.
      This case represents the first SILS Hartmann reversal via the colostomy site.
      METHODS: SILS Hartmann reversal was performed in a 56-year-old man with a history
      of resection for perforated diverticulitis. The procedure was performed via a
      single port placed into the former colostomy site. A combination of flexible and
      straight instruments was used. RESULTS: The procedure was completed successfully
      with an operative time of 104 minutes. Recovery was uneventful, and the patient
      was discharged on postoperative day 5, with no complaints at follow-up.
      CONCLUSION: SILS Hartmann procedure reversal via the colostomy site is safe. The
      approach avoids additional incisions and allows avoidance of dense adhesions to
      the previous midline incision--a new benefit of SILS, apart from cosmesis.

PMID- 21868422
TI  - Are pedicled flaps feasible in robotic surgery? Report of an anatomical study of
      the kite flap in conventional surgery versus robotic surgery.
AB  - Reconstruction of cutaneous defects of the hand has dramatically progressed. It
      should also benefit from the development of robot-assisted surgery. The aim of
      the present study was to consider the feasibility of a kite flap in robotic
      surgery. Two cadaver hands were used in this study, one for a conventional
      procedure, and one for a robotic surgical procedure using a da Vinci Si robot.
      The operative duration was measured, and all difficulties encountered during the
      procedures were reported. The total duration of the intervention was 19 minutes
      with the conventional procedure and 30 minutes with the robotic technique. Some
      difficulties were encountered, related both to lack of specific instrumentation
      and haptic feedback. Robotic surgery presents interesting advantages such as the
      suppression of physiological tremor, increased degrees of freedom, and enhanced
      precision and accuracy of hand maneuvers. In this study, it allowed the
      realization of a pedicled flap without any external help.

PMID- 21868423
TI  - "All eyes are on you": anorexia nervosa patient perspectives of in-patient
      mealtimes.
AB  - The aim of this qualitative study was to investigate in-patient perceptions of
      mealtimes on eating disorders units. Individual interviews were conducted with 12
      women with anorexia nervosa. Using thematic analysis, three themes emerged as
      important: 1) Mealtime delivery (logistical factors influencing meals); 2)
      Individual outcomes (cognitions, emotions, behaviours and physical sensations
      during meals); and 3) Mealtime characteristics (including disengagement,
      perceived battlegrounds, and a desire for involvement in mealtimes). Future
      research should focus on areas of treatment delivery identified as important by
      patients. Recommendations are made regarding mealtime protocols based on
      patients' views, with increased recognition of behavioural, cognitive, physical
      and emotional aspects.

PMID- 21868424
TI  - Goals with limited vision: a qualitative study of coping with vision-related goal
      interference in midlife.
AB  - OBJECTIVE: To investigate how middle-aged adults manage their goal pursuits in
      the face of visual disability. DESIGN: Cross-sectional qualitative study.
      SETTING: Vision rehabilitation agency. SUBJECTS: 216 middle-aged adults with
      visual impairment. METHODS: Telephone interviews composed of structured and open
      ended assessments of life goals and the strategies used to cope with vision
      related goal interference. RESULTS: Individuals reported strategies that
      reflected the broader domains found in prior research with older adults: internal
      resource use, new approach use, technology use, help use, and psychological self
      regulation. The most frequently reported strategy was help use (n = 192),
      followed by new approach use (n = 166), internal resource use (n = 162),
      technology use (n = 159) and psychological self-regulation (n = 130). Across
      domains, the most frequently reported strategies were instrumental informal help,
      instrumental formal help, optical aids, and invest effort. Specific strategy
      domains emerged as more typical in response to interference with particular types
      of goals; for example, help use was reported by a majority for interference with
      functional and psychological goals, but only by half for interference with social
      goals. CONCLUSIONS: Study findings revealed a rich array of strategies used by
      middle-aged adults with vision impairment in their daily lives to deal with
      vision-related goal interference. Results suggest that rehabilitation services
      should consider multiple methods of coping and their goal-related function when
      working with middle-aged adults with disabilities.

PMID- 21868425
TI  - The experience of physicians who refer Latinos to hospice.
AB  - This study explores the referral experience of physicians who refer Latinos to
      end-of-life care and challenges associated with the referral process. Qualitative
      data were collected in New Jersey through semistructured, open-ended interviews.
      Six physicians participated in this study: 1 oncologist, 2 internists, 1
      gerontologist, and 2 infectious disease specialists. The study reveals that
      language barriers, level of family involvement, and generational group of the
      patient and the family contribute to the complexity of the physician's
      experience. Physicians' comments evidence the importance of culturally competent
      training in medical school and continued education on this topic for physicians
      who did not receive such training. Bilingual bicultural hospice admissions' staff
      available at the physician's office could enhance the referral experience.

PMID- 21868426
TI  - Intrathecal morphine pump for neuropathic cancer pain: a case report.
AB  - The WHO ladder has been the most widely used approach for management of Cancer
      Pain. However, oral medications alone may be inadequate, particularly in
      difficult to treat cancer pain syndromes. Neuropathic pain is one of these
      refractory syndromes. The role of opioids has always been controversial in pain
      of neuropathic origin. We report a case of a 61 year old female patient with
      endometrial carcinoma suffering from severe neuropathic pain in her left lower
      limb. The pain was refractory to highest tolerable doses of oral morphine and
      neuromodulator drugs, viz. gabapentin and pregabalin. We managed the patient
      successfully with intrathecal morphine pump reducing the total morphine dose and
      improving patient comfort and satisfaction. Intrathecal delivery of Morphine
      ensured better efficacy with fewer side effects.

PMID- 21868427
TI  - Assessing challenges in end-of-life conversations with elderly patients with
      multiple morbidities.
AB  - INTRODUCTION: This study reports on physicians' experiences in conducting end-of
      life conversations with elderly patients who suffered from multiple co
      morbidities (MCM). Our hypothesis was that both the lack of prognostic certainty
      and the lack of good communication tools contributed to physicians' discomfort
      with conducting EOL conversations with patients and families of patients with
      these conditions especially when compared with patients and families of patients
      who had a single, clear terminal diagnosis (e.g. pancreatic cancer). METHODS:
      Focus group questions were semi-structured and explored three general themes: (1)
      differences between having an end-of-life conversation with patients/families
      with MCM versus those with a single, terminal diagnosis; (2) timing of the end-of
      life conversation; and (3) approaches to the end-of-life conversation. RESULTS:
      Three themes emerged: (1) It is more difficult for them to have EOL conversations
      with patients with MCM and their families, as opposed to conversations with
      families and patients who have a clear, terminal diagnosis. (2) In deciding when
      to raise the subject of EOL care, participants reported that they rely on a
      number of physical and/or social signs to prompt these discussions. Yet a major
      reason for the difficulty that providers face in initiating these discussions
      with MCM patients and families is that there is a lack of a clear threshold or
      prompting event. (3) Participants mentioned three types of approaches to
      initiating EOL conversations: (a) direct approach, (b) indirect approach, (c)
      collaborative approach. CONCLUSION: Prognostic indicies and communication scripts
      may better prepare physicians to facilitate end-of-life conversations with MCM
      patients/families.

PMID- 21868428
TI  - The relationship between cancer pain and quality of life in patients newly
      admitted to Wuhan Hospice Center of China.
AB  - To evaluate the relationship between pain and quality of life (QoL) in patients
      newly admitted to Wuhan Hospice Center, China. A total of 1,634 patients were
      analyzed in this retrospective study. A Numerical Rating Scale and Chinese-QoL
      instrument were used to assess pain score and QoL, respectively. Most patients
      experienced moderate to severe pain, which significantly impaired QoL. The pain
      was significantly correlated with appetite, mood, sleep, fatigue, pain intensity,
      daily activity, side effect, general appearance, and support from family. But
      there was no correlation with support from society, understanding of cancer, or
      attitude toward treatment. In our study, the relationship between pain and QoL
      was found to be reciprocal. The staff can offer a multidisciplinary care
      perspective for improving hospice care for this special group of population.

PMID- 21868429
TI  - Advance directives: limitations to completion.
AB  - The number of elderly persons is expected to increase to 55 million by 2020, with
      the minority population increasing to 12.9 million, yet fewer than 30% of
      Americans have advance directives in place. Cultural values, religious beliefs,
      and family support systems are a few of the factors that influence or hinder the
      completion of advance directives. Health care provider perspectives regarding
      advance directives vary greatly with health care settings. Many primary care
      providers are reluctant to initiate conversations regarding advance directives
      for multiple reasons. Nurse practitioners cover more than 600 million office
      visits per year in the United States and are in a key position to educate,
      advocate, and assist in the completion of advance directives.

PMID- 21868430
TI  - Hospice-assisted death? A study of Oregon hospices on death with dignity.
AB  - Nearly 90% of terminally ill patients who have used Oregon's distinctive death
      with dignity law to receive a medication to end their lives are enrolled in
      hospice care programs. In 2009-2010, we conducted a study of the policies
      developed by Oregon hospices to address patient inquiries and requests for death
      with dignity. The study examined the stated hospice values and positions and
      identified the boundaries to participation drawn by the hospice programs to
      protect personal and programmatic integrity. The boundaries were drawn around 6
      key caregiving considerations: (1) language regarding physician-assisted death
      (PAD); (2) informed decision making by patients; (3) collaboration with
      physicians; (4) provision of lethal medication; (5) assistance in the patient's
      act of taking the medication; and (6) staff presence at the time of medication
      ingestion.

PMID- 21868431
TI  - Feigning terminal illness to get narcotics: a cautionary tale for hospices.
AB  - We present the case of a woman who enrolled in the hospice benefit in order to
      obtain narcotics. We believe this is a cautionary tale for hospices because of
      our propensity to enroll patients with minimal corroborating information, in
      order not to delay symptom management. Also we are philosophically predisposed to
      believe a patient's self-report of pain and other distressing symptoms.

PMID- 21868432
TI  - Brain diffuse large B-cell lymphoma in a systemic lupus erythematosus patient
      treated with immunosuppressive agents including mycophenolate mofetil.

PMID- 21868433
TI  - Inflammatory biomarkers and oxidative stress measurements in patients with
      systemic lupus erythematosus with or without metabolic syndrome.
AB  - The aims of the present study were to report the frequency of metabolic syndrome
      in systemic lupus erythematosus (SLE); to verify differences in inflammatory
      biomarkers and oxidative stress in SLE patients with or without metabolic
      syndrome; and to assess which metabolic syndrome components are associated with
      oxidative stress and disease activity. The study included 58 SLE patients and 105
      controls. SLE patients were divided in two groups, with and without metabolic
      syndrome. 41.4% patients met the criteria for metabolic syndrome compared with
      10.5% controls. Patients with SLE and metabolic syndrome had significantly raised
      serum uric acid, C-reactive protein (CRP), lipid hydroperoxides, and protein
      oxidation when compared with patients with SLE without metabolic syndrome. Lipid
      hydroperoxides were correlated with CRP, whereas protein oxidation was associated
      with waist circumference and uric acid. There was a positive association between
      serum C3 and C4 and glucose and between C3 and CRP. SLE disease activity index
      (SLEDAI) scores were positively correlated with body mass index (BMI) and waist
      circumference (WC). In conclusion, SLE patients have a high prevalence of
      metabolic syndrome and this syndrome directly contributes to increase
      inflammatory status and oxidative stress. Inflammatory processes, being
      overweight/obese, and uric acid may favor oxidative stress increases in patients
      with SLE and metabolic syndrome. C3 and C4 may have a positive acute-phase
      protein behavior in patients with SLE.

PMID- 21868434
TI  - Historical and clinical features of 200 cases of equine sinus disease.
AB  - The historical and clinical findings in 200 referred cases of equine sinus
      disease were reviewed retrospectively. Univariable and multivariable analyses
      were performed to detect significant differences in historical or clinical
      features between various categories of sinus disease. The causes of sinus disease
      were classified as subacute primary (less than two months duration) (n=52),
      chronic primary (more than two months duration) (n=37), dental (n=40), sinus cyst
      (n=26), traumatic (n=13) or mycotic sinusitis (n=7), sinus neoplasia (n=10),
      dental-related oromaxillary fistula (n=8) and intrasinus progressive ethmoid
      haematoma (n=7). The majority of sinus disorders were of chronic duration at the
      time of referral and most (including 97 per cent of chronic primary sinusitis
      cases) had not responded to previous antibiotic therapy and/or sinus lavage in
      some cases. Clinical signs included unilateral nasal discharge in most cases,
      including purulent or mucopurulent discharge in all horses with primary, dental
      and mycotic sinusitis. Haemorrhagic nasal discharge was a feature of traumatic
      sinusitis and intrasinus progressive ethmoid haematomas. Firm facial swellings
      and nasal airflow obstruction were features of sinus cysts and neoplasms.
      Ipsilateral lymphadenitis was a more prominent feature of sinus disease with
      active infections such as primary, dental or mycotic sinusitis.

PMID- 21868435
TI  - Associations between biovar and virulence factor genes in Pasteurella multocida
      isolates from pigs in Spain.
AB  - Two hundred and five isolates of Pasteurella multocida from pigs were
      phenotypically and genetically characterised by determining their biovar,
      capsular type, virulence-associated genes and pulsed-field gel electrophoresis
      (PFGE) profiles. All isolates were identified as P multocida subspecies multocida
      and most were assigned to biovar 3 (58 per cent) and biovar 2 (39.5 per cent).
      Biovar 1 represented 2.4 per cent of the isolates. According to the capsular
      type, the great majority of the isolates (79.0 per cent) belonged to capsular
      type A, 18.5 per cent belonged to capsular type D and 2.4 per cent were of
      capsular type F. All isolates harboured ompH, psl, oma87, ptfA, nanB, nanH, tonB,
      hgbA, sodA and sodC genes, while none of them possessed the transferrin-binding
      protein gene tbpA. The prevalence of toxA, pfhaA and hgbB genes was variable
      (7.8, 40.5 and 60.5 per cent of the isolates, respectively). After PFGE typing,
      isolates of biovar 2 and 3 were grouped in two different clusters (A and B) at a
      level of 45 per cent similarity. In addition, isolates of biovar 2 and 3
      exhibited statistically significant differences (P<0.05) in the virulence
      associated hgbB and pfhA genes (biovar 3 was hgbB(+) pfhA(-), while biovar 2 was
      hgbB- pfhA(+)).

PMID- 21868436
TI  - Impact of the national full herd depopulation policy on the recurrence of bovine
      tuberculosis in Irish herds, 2003 to 2005.
AB  - This study evaluated the impact of the Irish herd bovine tuberculosis (bTB)
      depopulation policy (depopulation, disinfection, contiguous testing and local
      badger removal where implicated) on the recurrence of bTB infection, by comparing
      the future risk in restocked herds following depopulation for either bTB or
      bovine spongiform encephalopathy (BSE) during 2003 to 2005. Each herd was
      assigned a 'previous bTB risk', based on bTB history during the five years before
      depopulation. Future bTB risk was estimated, using a multivariable Cox
      proportional hazard model for time-to-breakdown for each study herd, to identify
      risk factors associated with bTB. Future bTB risk varied significantly by reason
      for depopulation and previous bTB risk. Herds depopulated for bTB (by definition,
      at high bTB risk) were not significantly different from BSE herds with no or a
      low previous bTB risk. BSE herds with a high previous bTB risk were found to be
      at significantly greater future bTB risk. Herd bTB depopulation measures, as
      currently applied in Ireland, are shown to be effective in enabling herds to
      attain and retain bTB freedom following restocking. Based on the data presented,
      and consistent with current knowledge of the bTB epidemiology, local badger
      removal contributes to efforts to limit recurrence of bTB in Ireland.

PMID- 21868437
TI  - Canine adder bites in the UK: a retrospective study of cases reported to the
      Veterinary Poisons Information Service.
AB  - This retrospective study examined cases with follow-up reported to the Veterinary
      Poisons Information Service (VPIS) between September 1985 and December 2010. Most
      bites (69.2 per cent) occurred between April and July, particularly between 15:00
      and 16:00 hours. Adder bites were more frequently reported in the south-east of
      England, particularly in Surrey. Swelling to the face and limbs was common, as
      was lethargy, depression, hyperthermia and tachycardia. About two-thirds of dogs
      developed both systemic and local effects, while a third developed local effects
      alone. Initial clinical effects usually occurred within two hours, with full
      recovery typically occurring five days after the bite. Antivenom was used in 55.9
      per cent of cases and appeared to significantly reduce duration of oedema from an
      average of 94 to 47 hours. Adder bites can cause significant morbidity (97 per
      cent of dogs were symptomatic), but mortality is low (4.6 per cent died).

PMID- 21868439
TI  - Olfactory learning-induced enhancement of the predisposition for LTP induction.
AB  - Learning of a particularly difficult olfactory-discrimination (OD) task results
      in acquisition of rule learning. This enhancement in learning capability is
      accompanied by the long-term enhancement of synaptic connectivity between
      piriform cortex pyramidal neurons. In this study we examined whether olfactory
      rule learning would modify the predisposition to induce long-term potentiation
      (LTP) in the pathway projecting from the piriform cortex to the olfactory bulb.
      We report that OD learning was associated with enhancement in the predisposition
      to induce LTP. This learning-related effect may be affected by process generation
      of new granule cells located in the olfactory bulb.

PMID- 21868438
TI  - Epigenetic alterations in the lateral amygdala are required for reconsolidation
      of a Pavlovian fear memory.
AB  - Epigenetic mechanisms have been widely implicated in synaptic plasticity and in
      memory consolidation, yet little is known about the role of epigenetic mechanisms
      in memory reconsolidation processes. In the present study, we systematically
      examine the role of histone acetylation and DNA methylation in the
      reconsolidation of an amygdala-dependent Pavlovian fear memory. We first show
      that the acetylation of histone 3 (H3), but not histone 4 (H4), is regulated
      following auditory fear memory retrieval in the lateral nucleus of the amygdala
      (LA). We next show that histone deacetylase (HDAC) inhibition in the LA enhances
      both retrieval-induced histone acetylation and reconsolidation of an auditory
      fear memory. Conversely, inhibition of DNA methytransferase (DNMT) activity in
      the LA significantly impairs both retrieval-related H3 acetylation and fear
      memory reconsolidation. The effects of HDAC and DNMT inhibitors on fear memory
      reconsolidation were observed to be time-limited and were not evident in the
      absence of memory reactivation. Further, memories lost following DNMT inhibition
      were not observed to be vulnerable to spontaneous recovery, reinstatement, or to
      a shift in testing context, suggesting that memory impairment was not the result
      of facilitated extinction. Finally, pretreatment with the HDAC inhibitor was
      observed to rescue the reconsolidation deficit induced by the DNMT inhibitor.
      These findings collectively suggest that histone acetylation and DNA methylation
      are critical for reconsolidation of fear memories in the LA.

PMID- 21868440
TI  - Forum Theatre for Bystanders: a new model for gender violence prevention.
AB  - This article introduces the "Forum Theatre for Bystanders" (FTB) approach to
      gender violence prevention as practiced by social change groups at several
      midwestern universities in the United States. Largely informed by Augusto Boal's
      Theatre of the Oppressed and contemporary research on bystander theory, the Forum
      Theatre for Bystanders model offers a community-based approach that increases
      bystander responsibility and reduces victim blaming. The authors describe this
      model in detail and offer examples from their work to demonstrate its usefulness
      and efficacy.

PMID- 21868447
TI  - Appraising contemporary strategies to combat multidrug resistant gram-negative
      bacterial infections--proceedings and data from the Gram-Negative Resistance
      Summit.
AB  - The emerging problem of antibiotic resistance, especially among Gram-negative
      bacteria (GNB), has become a serious threat to global public health. Very few new
      antibacterial classes with activity against antibiotic-resistant GNB have been
      brought to market. Renewed and growing attention to the development of novel
      compounds targeting antibiotic-resistant GNB, as well as a better understanding
      of strategies aimed at preventing the spread of resistant bacterial strains and
      preserving the efficacy of existing antibiotic agents, has occurred. The Gram
      Negative Resistance Summit convened national opinion leaders for the purpose of
      analyzing current literature, epidemiologic trends, clinical trial data,
      therapeutic options, and treatment guidelines related to the management of
      antibiotic-resistant GNB infections. After an in-depth analysis, the Summit
      investigators were surveyed with regard to 4 clinical practice statements. The
      results then were compared with the same survey completed by 138 infectious
      disease and critical care physicians and are the basis of this article.

PMID- 21868449
TI  - Gene repressive activity of RIP140 through direct interaction with CDK8.
AB  - Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear
      receptors and transcription factors and primarily exerts gene-repressive
      activities on various target genes. We previously identified a spectrum of
      posttranslational modifications on RIP140 that augment its property and
      biological activity. In T(3)-triggered biphasic regulation of cellular retinoic
      acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte
      differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin
      remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of
      this gene promoter. In this current study, we aim to examine whether and how
      RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte
      cultures. We find increasing recruitment of RIP140 to this promoter, with
      corresponding reduction in TRAP220(MED1) recruitment during the T(3)-repressive
      phase. We also uncover direct interaction of RIP140 with cyclin-dependent kinase
      (CDK)8 through the amino terminus of RIP140, which is stimulated by lysine
      acetylation on RIP140. We further validate the biological activity of lysine
      acetylation-mimetic RIP140, which elicits a stronger repressive effect and more
      efficiently recruits CDK8 and confirm CDK8's function in recruiting repressive
      components, such as G9a, to the RIP140 complex on this promoter. This underlies
      the T(3)-triggered repression of CrabpI gene. This study illustrates a new gene
      repressive mechanism of RIP140 that can affect the transcription machinery by
      directly interacting with CDK8.

PMID- 21868450
TI  - cGMP inhibits TGF-beta signaling by sequestering Smad3 with cytosolic beta2
      tubulin in pulmonary artery smooth muscle cells.
AB  - Atrial natriuretic peptide (ANP) and TGF-beta play counterregulatory roles in
      pulmonary vascular adaptation to chronic hypoxia. We have demonstrated that ANP
      cyclic GMP (cGMP)-protein kinase G (PKG) signaling inhibits TGF-beta signaling by
      blocking TGF-beta-induced nuclear translocation of mothers against
      decapentaplegic homolog (Smad)3 in pulmonary artery smooth muscle cells (PASMC).
      The current study tested the novel hypothesis that activation of the ANP-cGMP-PKG
      pathway limits TGF-beta-induced Smad3 nuclear translocation by enhancing Smad3
      binding to cytosolic anchoring proteins in isolated pulmonary artery smooth
      muscle cells. Cells were pretreated with vehicle or cGMP and then exposed to TGF
      beta1 treatment. Cytosolic fractions were isolated and immunoprecipitated with a
      selective anti-Smad3 antibody. Differential proteomic analysis of the cytosolic
      Smad3-interacting proteins by two-dimensional differential in-gel electrophoresis
      and mass spectroscopy followed by coimmunoprecipitation and immunostaining
      demonstrated that Smad3 was bound to beta2-tubulin in a TGF-beta1/cGMP-dependent
      manner: binding of Smad3 to beta2-tubulin was decreased by TGF-beta1 and
      increased by cGMP treatment. A site-directed mutagenesis study demonstrated that
      mutating Smad3 at Thr388, but not Ser309, two potential sites of PKG-induced
      hyperphosphorylation, inhibited cGMP-induced Smad3 binding to beta2-tubulin.
      Further, luciferase reporter analysis showed that muation of T388 in Smad3
      abolished the inhibitory effect of cGMP on TGF-beta1-induced plasminogen
      activator inhibitor-1 (PAI-1) transcription. In addition, disruption of beta2
      tubulin with the microtubule depolymerizers nocodazole and colchicine promoted
      Smad3 dissociation from beta2-tubulin, increased both TGF-beta1-induced Smad3
      nuclear translocation and PAI-1 mRNA expression, and abolished the inhibitory
      effects of cGMP on these processes. In contrast, the microtubule stabilizers
      paclitaxel and epothilone B increased cytosolic Smad3 binding to beta2-tubulin
      and enhanced the inhibitory effect of cGMP on Smad3 nuclear translocation and PAI
      1 expression in response to TGF-beta1. These provocative findings suggest that
      sequestering Smad3 by beta2-tubulin in cytosol is a key mechanism by which ANP
      cGMP-PKG signaling interferes with downstream signaling from TGF-beta and thus
      protects against pulmonary arterial remodeling in response to hypoxia stress.

PMID- 21868451
TI  - The estrogen-regulated transcription factor PITX1 coordinates gene-specific
      regulation by estrogen receptor-alpha in breast cancer cells.
AB  - The estrogen receptor alpha (ERalpha) is a master regulator of gene expression
      and works along with cooperating transcription factors in mediating the actions
      of the hormone estradiol (E2) in ER-positive tissues and breast tumors. Here, we
      report that expression of paired-like homeodomain transcription factor (PITX1), a
      tumor suppressor and member of the homeobox family of transcription factors, is
      robustly up-regulated by E2 in several ERalpha-positive breast cancer cell lines
      via ERalpha-dependent interaction between the proximal promoter and an enhancer
      region 5' upstream of the PITX1 gene. Overexpression of PITX1 selectively
      inhibited the transcriptional activity of ERalpha and ERbeta, while enhancing the
      activities of the glucocorticoid receptor and progesterone receptor. Reduction of
      PITX1 by small interfering RNA enhanced ERalpha-dependent transcriptional
      regulation of a subset of ERalpha target genes. The consensus PITX1 binding motif
      was found to be present in 28% of genome-wide ERalpha binding sites and was in
      close proximity to estrogen response elements in a subset of ERalpha binding
      sites, and E2 treatment enhanced PITX1 as well as ERalpha recruitment to these
      binding sites. These studies identify PITX1 as a new ERalpha transcriptional
      target that acts as a repressor to coordinate and fine tune target-specific,
      ERalpha-mediated transcriptional activity in human breast cancer cells.

PMID- 21868452
TI  - Residues within the transmembrane domain of the glucagon-like peptide-1 receptor
      involved in ligand binding and receptor activation: modelling the ligand-bound
      receptor.
AB  - The C-terminal regions of glucagon-like peptide-1 (GLP-1) bind to the N terminus
      of the GLP-1 receptor (GLP-1R), facilitating interaction of the ligand N terminus
      with the receptor transmembrane domain. In contrast, the agonist exendin-4 relies
      less on the transmembrane domain, and truncated antagonist analogs (e.g. exendin
      9-39) may interact solely with the receptor N terminus. Here we used mutagenesis
      to explore the role of residues highly conserved in the predicted transmembrane
      helices of mammalian GLP-1Rs and conserved in family B G protein coupled
      receptors in ligand binding and GLP-1R activation. By iteration using information
      from the mutagenesis, along with the available crystal structure of the receptor
      N terminus and a model of the active opsin transmembrane domain, we developed a
      structural receptor model with GLP-1 bound and used this to better understand
      consequences of mutations. Mutation at Y152 [transmembrane helix (TM) 1], R190
      (TM2), Y235 (TM3), H363 (TM6), and E364 (TM6) produced similar reductions in
      affinity for GLP-1 and exendin 9-39. In contrast, other mutations either
      preferentially [K197 (TM2), Q234 (TM3), and W284 (extracellular loop 2)] or
      solely [D198 (TM2) and R310 (TM5)] reduced GLP-1 affinity. Reduced agonist
      affinity was always associated with reduced potency. However, reductions in
      potency exceeded reductions in agonist affinity for K197A, W284A, and R310A,
      while H363A was uncoupled from cAMP generation, highlighting critical roles of
      these residues in translating binding to activation. Data show important roles in
      ligand binding and receptor activation of conserved residues within the
      transmembrane domain of the GLP-1R. The receptor structural model provides
      insight into the roles of these residues.

PMID- 21868453
TI  - Connective tissue growth factor is required for normal follicle development and
      ovulation.
AB  - Connective tissue growth factor (CTGF) is a cysteine-rich protein the synthesis
      and secretion of which are hypothesized to be selectively regulated by activins
      and other members of the TGF-beta superfamily. To investigate the in vivo roles
      of CTGF in female reproduction, we generated Ctgf ovarian and uterine conditional
      knockout (cKO) mice. Ctgf cKO mice exhibit severe subfertility and multiple
      reproductive defects including disrupted follicle development, decreased
      ovulation rates, increased numbers of corpus luteum, and smaller but functionally
      normal uterine horns. Steroidogenesis is disrupted in the Ctgf cKO mice, leading
      to increased levels of serum progesterone. We show that disrupted follicle
      development is accompanied by a significant increase in granulosa cell apoptosis.
      Moreover, despite normal cumulus expansion, Ctgf cKO mice exhibit a significant
      decrease in oocytes ovulated, likely due to impaired ovulatory process. During
      analyses of mRNA expression, we discovered that Ctgf cKO granulosa cells show
      gene expression changes similar to our previously reported granulosa cell
      specific knockouts of activin and Smad4, the common TGF-beta family intracellular
      signaling protein. We also discovered a significant down-regulation of Adamts1, a
      progesterone-regulated gene that is critical for the remodeling of extracellular
      matrix surrounding granulosa cells of preovulatory follicles. These findings
      demonstrate that CTGF is a downstream mediator in TGF-beta and progesterone
      signaling cascades and is necessary for normal follicle development and
      ovulation.

PMID- 21868454
TI  - Management of hypertension: summary of NICE guidance.

PMID- 21868455
TI  - Magnitude, impact, and stability of primary headache subtypes: 30 year
      prospective Swiss cohort study.
AB  - OBJECTIVE: To determine the prevalence, impact, and stability of different
      subtypes of headache in a 30 year prospective follow-up study of a general
      population sample. DESIGN: Prospective cohort study. SETTING: Canton of Zurich,
      Switzerland. PARTICIPANTS: 591 people aged 19-20 from a cohort of 4547 residents
      of Zurich, Switzerland, interviewed seven times across 30 years of follow-up.
      MAIN OUTCOME MEASURES: Prevalence of headache; stability of the predominant
      subtype of headache over time; and age of onset, severity, impact, family
      history, use of healthcare services, and drugs for headache subtypes. RESULTS:
      The average one year prevalences of subtypes of headache were 0.9% (female:male
      ratio of 2.8) for migraine with aura, 10.9% (female:male ratio of 2.2) for
      migraine without aura, and 11.5% (female:male ratio of 1.2) for tension-type
      headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for
      migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type
      headache. Despite the high prevalence of migraine without aura, most cases were
      transient and only about 20% continued to have migraine for more than half of the
      follow-up period. 69% of participants with migraine and 58% of those with tension
      type headache manifested the same predominant subtype over time. However, the
      prospective stability of the predominant headache subtypes was quite low, with
      substantial crossover among the subtypes and no specific ordinal pattern of
      progression. A gradient of severity of clinical correlates and service use was
      present across headache subtypes; the greatest effect was for migraine with aura
      followed by migraine without aura, and then tension-type headache and
      unclassified headaches. CONCLUSIONS: These findings highlight the importance of
      prospective follow-up of people with headache. The substantial longitudinal
      overlap among subtypes of headache shows the developmental heterogeneity of
      headache syndromes. Studies of the causes of headache that apply diagnostic
      nomenclature based on distinctions between discrete headache subtypes may not
      capture the true nature of headache in the general population.

PMID- 21868456
TI  - Investigating mixed hyperlipidaemia.

PMID- 21868458
TI  - Portugal caps locum fees to meet financial bail out requirements.

PMID- 21868457
TI  - Speech and language delays in preschool children.

PMID- 21868459
TI  - Use of strong opioids in Canada rose sharply between 2005 and 2010.

PMID- 21868460
TI  - Pilot scheme shows that giving naloxone to families of drug users would save
      lives.

PMID- 21868461
TI  - US research agency halves threshold for reporting financial conflicts of
      interest.

PMID- 21868462
TI  - Rise in assisted reproduction tourism in Asia threatens local medical services.

PMID- 21868463
TI  - Central airway stabilization for tracheobronchomalacia improves quality of life
      in patients with COPD.
AB  - BACKGROUND: Tracheobronchomalacia (TBM) is characterized by excessive
      collapsibility of the central airways, typically during expiration. TBM may be
      present in as many as 50% of patients evaluated for COPD. The impact of central
      airway stabilization on symptom pattern and quality of life is poorly understood
      in this patient population. METHODS: Patients with documented COPD were
      identified from a cohort of 238 patients assessed for TBM at our complex airway
      referral center. Pulmonary function testing, exercise tolerance, and health
      related quality-of-life (HRQOL) measures were assessed at baseline and 2 to 4
      weeks following tracheal stent placement/operative tracheobronchoplasty (TBP).
      Severity of COPD was classified according to the GOLD (Global Initiative for
      Chronic Obstructive Lung Disease) staging system. RESULTS: One hundred three
      patients (48 women) with COPD and moderately severe to severe TBM were
      identified. Statistically and clinically significant improvements were seen in
      HRQOL measures, including the transitional dyspnea index (stent, P = .001; TBP, P
      = .008), the St. George Respiratory Questionnaire (stent, P = .002; TBP, P <
      .0001), and the Karnofsky performance score (stent, P = .163; TBP, P < .0001).
      The improvement appeared greatest following TBP and was seen in all GOLD stages.
      Clinical improvement was also seen in measured FEV(1) and exercise capacity as
      assessed by 6-min walk test. CONCLUSIONS: Central airway stabilization may
      provide symptomatic benefit for patients with severe COPD and concomitant severe
      airway malacia. Operative airway stabilization appears to impart the greatest
      advantage. Long-term follow-up study is needed to fully ascertain the ultimate
      efficacy of both stenting and surgical airway stabilization in this patient
      group.

PMID- 21868464
TI  - Postoperative complications in patients with obstructive sleep apnea.
AB  - BACKGROUND: Unrecognized obstructive sleep apnea (OSA) is associated with
      unfavorable perio-perative outcomes among patients undergoing noncardiac surgery
      (NCS). METHODS: The study population was chosen from 39,771 patients who
      underwent internal medicine preoperative assessment between January 2002 and
      December 2006. Patients undergoing NCS within 3 years of polysomnography (PSG)
      were considered for the study, whereas those < 18 years of age, with a history of
      upper airway surgery, or who had had minor surgery under local or regional
      anesthesia were excluded. Patients with an apnea-hypopnea index (AHI) >= 5 were
      defined as OSA and those with an AHI < 5 as control subjects. For adjusting
      baseline differences in age, sex, race, BMI, type of anesthesia, American Society
      of Anesthesiology class, and medical comorbidities, the patients were classified
      into five quintiles according to a propensity score. RESULTS: Out of a total of
      1,759 patients who underwent both PSG and NCS, 471 met the study criteria. Of
      these, 282 patients had OSA, and the remaining 189 served as control subjects.
      The presence of OSA was associated with a higher incidence of postoperative
      hypoxemia (OR, 7.9; P = .009), overall complications (OR, 6.9; P = .003), and ICU
      transfer (OR, 4.43; P = .069), and a longer hospital length of stay (LOS), (OR,
      1.65; P = .049). Neither an AHI nor use of continuous positive airway pressure at
      home before surgery was associated with postoperative complications (P = .3 and P
      = .75, respectively) or LOS (P = .97 and P = .21, respectively). CONCLUSIONS:
      Patients with OSA are at higher risk of postoperative hypoxemia, ICU transfers,
      and longer hospital stay.

PMID- 21868465
TI  - The relationship of asthma impairment determined by psychometric tools to future
      asthma exacerbations.
AB  - BACKGROUND: Impairment and risk are considered separate domains of asthma
      control, but relationships between them are not completely understood. We
      compared three validated questionnaires reflecting asthma impairment in their
      ability to predict future exacerbations. METHODS: Two thousand six hundred eighty
      patients with persistent asthma completed a survey that included the Asthma
      Control Test (ACT), mini-Asthma Quality of Life Questionnaire (mAQLQ), and Asthma
      Impact Survey (AIS-6), as well as a history of exacerbations in the prior 12
      months. An exploratory factor analysis was performed using the questions of the
      three tools, and individual patient factor scores were calculated. Independent
      relationships between predictors (tools and factors) and exacerbations the
      following year captured from administrative data were evaluated. RESULTS: Each
      tool was significantly related (P < .0001) to future exacerbations above and
      beyond the risk conferred by prior exacerbations (relative risk [RR] = 1.3). When
      prior exacerbations were included in the model, the three impairment tools
      provided similar and overlapping information, such that only the mAQLQ entered
      the model (RR = 1.3; 95% CI, 1.1-1.5). Factor analysis revealed three factors
      (symptoms, activity, and bother) that were each significantly associated (P <
      .0001) with future asthma exacerbations. However, only the activity factor was
      independently related to future exacerbations. CONCLUSIONS: Asthma impairment is
      significantly related to the risk of future exacerbations, but the ACT, mAQLQ,
      and AIS-6 do not provide independent information from each other in this regard.
      Interference with activities is the primary subjective component of asthma
      impairment that is related to the risk of future exacerbations.

PMID- 21868466
TI  - Risk of misdiagnosis, health-related quality of life, and BMI in patients who are
      overweight with doctor-diagnosed asthma.
AB  - BACKGROUND: Obesity and asthma both cause breathlessness, and there is a risk of
      misdiagnosis of asthma in patients who are obese. Impaired health-related quality
      of life (HRQoL) and increased BMI increase physician attendance rates, increasing
      this risk. We explored the possibility of misdiagnosis and the relationship
      between BMI, HRQoL, and other traditional measures of asthma severity in subjects
      who were obese with a doctor's diagnosis of asthma. METHODS: Data were obtained
      from subjects who were overweight with physician-diagnosed asthma screened as
      part of another study, including bronchial provocative concentration of
      methacholine to produce a 20% fall in FEV(1) (PC(20)) or reversibility to
      bronchodilators, HRQoL measured using generic (Short Form-36 [SF-36]) and disease
      specific (St. George Respiratory Questionnaire and Impact of Weight on Quality of
      Life-Lite) questionnaires. The fraction of exhaled nitric oxide (Feno), height,
      weight, and atopic status were also recorded. RESULTS: Of 91 subjects (mean BMI,
      38 kg/m(2); mean FEV(1)%, 85.8%; mean FEV(1)/FVC, 70.0%; mean Feno, 25.1 parts
      per billion taking a mean chlorofluorocarbon-beclomethasone-equivalent dose of
      1,273.5 MUg/d), 36.3% had no bronchial hyperresponsiveness (possible
      misclassification of asthma diagnosis.) The BMI and HRQoL were significantly
      related: The St. George Respiratory Questionnaire total (r = 0.33, P < .001), SF
      36 physical health subtotal (r = -0.42, P < .001), SF-36 mental health subtotal
      (r = -0.39, P < .001), and Impact of Weight on Quality of Life-Lite total (r =
      0.51, P < .001) showed no relationship to airways inflammation and bronchial
      reactivity. There was no significant difference in quality-of-life scores in
      subjects with or without bronchial hyperreactivity. CONCLUSIONS: We found
      evidence of misdiagnosis of asthma in subjects who were obese. The BMI in
      subjects who were obese and had asthma negatively correlates with the HRQoL,
      which may relate to the diagnostic uncertainty and requires further exploration.
      TRIAL REGISTRY: ISRCTN Register; No.: 54432221; URL: www.controlled
      trials.com/isrctn.

PMID- 21868468
TI  - Test characteristics of ultrasonography for the detection of pneumothorax: a
      systematic review and meta-analysis.
AB  - BACKGROUND: A pneumothorax is a potentially life-threatening condition. Although
      CT scan is the reference standard for diagnosis, chest radiographs are commonly
      used to rule out the diagnosis. We compared the test characteristics of
      ultrasonography and supine chest radiography in adult patients clinically
      suspected of having a pneumothorax, using CT scan or release of air on chest tube
      placement as reference standard. METHODS: We searched for English literature in
      MEDLINE and EMBASE and performed hand searches. Two independent investigators
      used standardized forms to review articles for inclusion, quality (QUADAS tool),
      and data extraction. We calculated kappa agreement for study selection and
      evaluated clinical and quality homogeneity before meta-analysis. RESULTS: We
      reviewed 570 articles and selected 21 for full review (kappa, 0.89); eight
      articles (total of 1,048 patients) met all inclusion criteria (kappa, 0.81). All
      studies but one used the ultrasonographic signs of lung sliding and comet tail to
      rule out pneumothorax. Chest radiography data were available for 864 of 1,048
      patients evaluated with ultrasonography. Ultrasonography was 90.9% sensitive (95%
      CI, 86.5-93.9) and 98.2% specific (95% CI, 97.0-99.0) for the detection of
      pneumothorax. Chest radiography was 50.2% sensitive (95% CI, 43.5-57.0) and 99.4%
      specific (95% CI, 98.3-99.8). CONCLUSIONS: Performance of ultrasonography for the
      detection of pneumothorax is excellent and is superior to supine chest
      radiography. Considering the rapid access to bedside ultrasonography and the
      excellent performance of this simple test, this study supports the routine use of
      ultrasonography for the detection of pneumothorax.

PMID- 21868467
TI  - Obesity and right ventricular structure and function: the MESA-Right Ventricle
      Study.
AB  - BACKGROUND: The relationship between obesity and right ventricular (RV)
      morphology is not well studied. We aimed to determine the association between
      obesity and RV structure and function in a large multiethnic population-based
      cohort. METHODS: The MESA-Right Ventricle Study measured RV mass and volumes by
      cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular
      disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were
      divided into three categories based on BMI: lean ( <= 24.9 kg/m(2)), overweight
      (25-29.9 kg/m(2)), and obese ( >= 30 kg/m(2)). RESULTS: The study sample included
      4,127 participants. After adjustment for demographics, height, education, and
      cardiovascular risk factors, overweight and obese participants had greater RV
      mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and
      18% greater, respectively), larger RV stroke volume (7% and 16% greater,
      respectively), and lower RV ejection fraction ( >= 1% lower) than lean
      participants (all P < .001). These findings persisted after adjusting for the
      respective left ventricular (LV) parameters. CONCLUSIONS: Overweight and obesity
      were independently associated with differences in RV morphology even after
      adjustment for the respective LV measure. This association could be explained by
      increased RV afterload, increased blood volume, hormonal effects, or direct
      obesity-related myocardial effects.

PMID- 21868469
TI  - Benchmark data from more than 240,000 adults that reflect the current practice of
      critical care in the United States.
AB  - BACKGROUND: Nationwide benchmarks representing current critical care practice for
      the range of ICUs are lacking. This information may highlight opportunities for
      care improvement and allows comparison of ICU practice data. METHODS: Data
      representing 243,553 adult admissions from 271 ICUs and 188 US nonfederal
      hospitals during 2008 were analyzed using the eICU Research Institute clinical
      practice database. Participating ICUs and hospitals varied widely regarding bed
      number, community size, academic status, geographic location, and organizational
      structure. RESULTS: More than one-half of these critically ill adults were < 65
      years old, and most patients returned to their homes after hospital discharge.
      Most patients were admitted from an ED, had a medical admission diagnosis, and
      received antimicrobial therapy. Intensive treatment was common, including 27% who
      received mechanical ventilation, 7.5% who were supported with noninvasive
      ventilation, 24.3% who were treated with vasoactive infusions, > 20% who received
      a blood product, and 4.4% who agreed to a care limitation order during their ICU
      stay. Forty percent of cases had a < 10% mortality risk and did not have an
      intensive treatment documented. CONCLUSIONS: Admission to an ICU in 2008 involved
      active treatments that often included life support and counseling for those near
      the end of life and was associated with favorable outcomes for most patients.

PMID- 21868470
TI  - Independent and combined effects of ethanol self-administration and nicotine
      treatment on hepatic CYP2E1 in African green monkeys.
AB  - Cytochrome P450 2E1 metabolizes ethanol and also bioactivates many toxins and
      procarcinogens. Elevated levels of hepatic CYP2E1 are associated with an
      increased susceptibility to chemical toxicity and carcinogenesis. This study
      investigated the induction of hepatic CYP2E1 by ethanol and nicotine, alone and
      in combination, in a nonhuman primate model. Monkeys that self-administered
      ethanol and that received subcutaneous injections of nicotine (0.5 mg/kg b.i.d.),
      alone and in combination, were compared with control animals (four groups, n =
      10/group). Chlorzoxazone (CZN) was used as a probe drug to phenotype in vivo
      CYP2E1 activity before and after chronic ethanol and/or nicotine exposure. CYP2E1
      protein levels and in vitro chlorzoxazone metabolism were assessed in liver
      microsomes. Average daily ethanol consumption was ~3.0 g/kg (blood ethanol levels
      ~24 mM) and was unaffected by nicotine treatment. Ethanol self-administration and
      nicotine treatment, alone and in combination, significantly increased in vivo CZN
      disposition compared with that in control animals. The effect of ethanol was only
      observed at higher levels of intake. Ethanol and nicotine increased CYP2E1
      protein levels and in vitro CZN metabolism, with combined exposure to both drugs
      resulting in the greatest increase. The effect of ethanol was also dependent on
      level of intake. Chronic exposure to ethanol and nicotine induced hepatic CYP2E1
      activity and protein levels, particularly when both drugs were used in
      combination and when ethanol intake was high. These results have important
      implications for public health, given the association between elevated CYP2E1 and
      disease, and the large proportion of individuals who are exposed to ethanol and
      nicotine, often in combination.

PMID- 21868472
TI  - Endurance exercise training promotes medullary hematopoiesis.
AB  - Endurance exercise is a poorly defined yet powerful mediator of hematopoiesis.
      The purpose of this study was to directly investigate the effects of endurance
      exercise training on hematopoiesis and to identify potential mechanisms
      responsible for any observed changes. Four-week-old male C57Bl/6 mice were
      trained on a treadmill at progressive speeds over a 10-wk period. Tissues were
      harvested 2 d following the final training session. Flow cytometry, the
      cobblestone area-forming cell assay, and the methycellulose colony-forming unit
      assay were used to assess medullary and mobilized hematopoietic stem and
      progenitor cells. Quantitative real-time PCR and Western blots were used to
      measure hematopoietic cytokine production. Histochemistry was also used to assess
      adaptations to exercise in the bone marrow niche. Depending on the cell type,
      endurance training increased medullary and mobilized hematopoietic stem and
      progenitor cell content from 50 to 800%. Training also reduced marrow cavity fat
      by 78%. Skeletal muscle hematopoietic cytokine expression was also increased at
      least 60% by training. Sedentary mice served as controls for the above
      experiments. In conclusion, endurance exercise training greatly promotes
      hematopoiesis and does so through improvements in medullary niche architecture as
      well as increased skeletal muscle hematopoietic cytokine production.

PMID- 21868471
TI  - Cardiac arrest and therapeutic hypothermia decrease isoform-specific cytochrome
      P450 drug metabolism.
AB  - Mild therapeutic hypothermia is emerging clinically as a neuroprotection therapy
      for individuals experiencing cardiac arrest (CA); however, its effects combined
      with disease pathogenesis on drug disposition and response have not been fully
      elucidated. We determined the activities of four major hepatic-metabolizing
      enzymes (CYP3A, CYP2C, CYP2D, and CYP2E) during hypothermia after experimental CA
      in rats by evaluating the pharmacokinetics of their probe drugs as a function of
      altered body temperature. Animals were randomized into sham normothermia (37.5-38
      degrees C), CA normothermia, sham hypothermia (32.5-33 degrees C), and CA
      hypothermia groups. Probe drugs (midazolam, diclofenac, dextromethorphan, and
      chlorzoxazone) were given simultaneously by intravenous bolus after temperature
      stabilization. Multiple blood samples were collected between 0 and 8 h after drug
      administration. Pharmacokinetic (PK) analysis was conducted using a
      noncompartmental approach and population PK modeling. Noncompartmental analysis
      showed that the clearance of midazolam (CYP3A) in CA hypothermia was reduced from
      sham normothermia rats (681.6 +/- 190.0 versus 1268.8 +/- 348.9 ml . h(-1) . kg(
      1), p < 0.05). The clearance of chlorzoxazone (CYP2E) in CA hypothermia was also
      reduced from sham normothermia rats (229.6 +/- 75.6 versus 561.89 +/- 215.9 ml .
      h(-1) . kg(-1), p < 0.05). Population PK analysis further demonstrated the
      decreased clearance of midazolam (CYP3A) was associated with CA injury (p <
      0.05). The decreased clearance of chlorzoxazone (CYP2E1) was also associated with
      CA injury (p < 0.01). Hypothermia was found to be associated with the decreased
      volume of distribution of midazolam (V(1)), dextromethorphan (V(1)), and
      peripheral compartment for chlorzoxazone (V(2)) (p < 0.05, p < 0.05, and p <
      0.01, respectively). Our data indicate that hypothermia, CA, and their
      interaction alter cytochrome P450-isoform specific activities in an isoform
      specific manner.

PMID- 21868473
TI  - Phospholipase A2 superfamily members play divergent roles after spinal cord
      injury.
AB  - Spinal cord injury (SCI) results in permanent loss of motor functions. A
      significant aspect of the tissue damage and functional loss may be preventable as
      it occurs, secondary to the trauma. We show that the phospholipase A(2) (PLA(2))
      superfamily plays important roles in SCI. PLA(2) enzymes hydrolyze membrane
      glycerophospholipids to yield a free fatty acid and lysophospholipid. Some free
      fatty acids (arachidonic acid) give rise to eicosanoids that promote
      inflammation, while some lysophospholipids (lysophosphatidylcholine) cause
      demyelination. We show in a mouse model of SCI that two cytosolic forms [calcium
      dependent PLA(2) group IVA (cPLA(2) GIVA) and calcium-independent PLA(2) group
      VIA (iPLA(2) GVIA)], and a secreted form [secreted PLA(2) group IIA (sPLA(2)
      GIIA)] are up-regulated. Using selective inhibitors and null mice, we show that
      these PLA(2)s play differing roles. cPLA(2) GIVA mediates protection, whereas
      sPLA(2) GIIA and, to a lesser extent, iPLA(2) GVIA are detrimental. Furthermore,
      completely blocking all three PLA(2)s worsens outcome, while the most beneficial
      effects are seen by partial inhibition of all three. The partial inhibitor
      enhances expression of cPLA(2) and mediates its beneficial effects via the
      prostaglandin EP1 receptor. These findings indicate that drugs that inhibit
      detrimental forms of PLA(2) (sPLA(2) and iPLA2) and up-regulate the protective
      form (cPLA2) may be useful for the treatment of SCI.

PMID- 21868474
TI  - Quantitative validation of GJC1 promoter hypermethylation in benign and malignant
      colorectal tumors.
AB  - We have previously shown that the gap junction protein gamma 1 (GJC1) gene,
      encoding the connexin-45 protein, is inactivated by promoter hypermethylation in
      colorectal cancer. This was confirmed in a recent Endocrine-Related Cancer
      publication analyzing a limited number of samples. The aim of this study was to
      analyze GJC1 in a larger clinical cohort (n=485) and to assess whether or not the
      promoter hypermethylation was associated with clinical or pathological features.
      The methylation of GJC1 was confirmed to be tumor specific and was observed in
      33% of colorectal cancers and 12% of adenomas. The methylation was strongly
      associated with BRAF mutations (P=5.64*10(-13)) as well as with proximal tumor
      location (P=1.42*10(-3)), features compatible with a CpG island methylator
      phenotype.

PMID- 21868475
TI  - Undernutrition in adolescence and risk of cardiovascular disease.

PMID- 21868476
TI  - Cardiovascular consequences of famine in the young.
AB  - Aims The developmental origins hypothesis proposes that undernutrition during
      foetal life, infancy, or childhood is associated with an increased risk of
      cardiovascular disease in adulthood. As data on postnatal developmental
      programming are scarce, we investigated whether exposure to undernutrition during
      childhood, adolescence, or young adulthood is related to coronary heart disease
      (CHD) and stroke in adult life.  Methods and results We studied 7845 women from
      the Prospect-EPIC cohort who had been exposed at various degrees to the 1944-45
      Dutch famine when they were aged between 0 and 21 years. We used Cox proportional
      hazard regression models to explore the effect of famine on the risk of CHD and
      stroke, overall and within exposure age categories (0-9, 10-17, >=18 years). We
      adjusted for potential confounders, including age at famine exposure, smoking,
      and level of education as a proxy for socio-economic status. Overall, stronger
      famine exposure was associated with higher CHD risk. Among those who experienced
      the famine between ages 10 and 17 years, CHD risk was significantly higher among
      severely exposed women compared with unexposed women (HR 1.38; 95% CI 1.03-1.84),
      which only slightly attenuated after adjustment for confounding (HR 1.27; 95% CI
      0.94-1.71). We observed a lower stroke risk among famine exposed women (HR 0.79;
      95% CI 0.61-1.02). Adjustment for potential confounders produced similar results
      (HR 0.77; 95% CI 0.59-0.99).  Conclusion Exposure to undernutrition during
      postnatal periods of development, including adolescence, may affect
      cardiovascular health in adult life.

PMID- 21868477
TI  - Development of prognosis in palliative care study (PiPS) predictor models to
      improve prognostication in advanced cancer: prospective cohort study.
AB  - OBJECTIVE: To develop a novel prognostic indicator for use in patients with
      advanced cancer that is significantly better than clinicians' estimates of
      survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18
      palliative care services in the UK (including hospices, hospital support teams,
      and community teams). PARTICIPANTS: 1018 patients with locally advanced or
      metastatic cancer, no longer being treated for cancer, and recently referred to
      palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model
      to predict whether patients were likely to survive for "days" (0-13 days),
      "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and
      clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables
      (pulse rate, general health status, mental test score, performance status,
      presence of anorexia, presence of any site of metastatic disease, presence of
      liver metastases, C reactive protein, white blood count, platelet count, and
      urea) independently predicted both two week and two month survival. Four
      variables had prognostic significance only for two week survival (dyspnoea,
      dysphagia, bone metastases, and alanine transaminase), and eight variables had
      prognostic significance only for two month survival (primary breast cancer, male
      genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count,
      alkaline phosphatase, and albumin). Separate prognostic models were created for
      patients without (PiPS-A) or with (PiPS-B) blood results. The area under the
      curve for all models varied between 0.79 and 0.86. Absolute agreement between
      actual survival and PiPS predictions was 57.3% (after correction for over
      optimism). The median survival across the PiPS-A categories was 5, 33, and 92
      days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models
      performed as well as, or better than, clinicians' estimates of survival.
      CONCLUSIONS: In patients with advanced cancer no longer being treated, a
      combination of clinical and laboratory variables can reliably predict two week
      and two month survival.

PMID- 21868479
TI  - Predicting and communicating prognosis in palliative care.

PMID- 21868478
TI  - Vitamin A supplements for preventing mortality, illness, and blindness in
      children aged under 5: systematic review and meta-analysis.
AB  - OBJECTIVE: To determine if vitamin A supplementation is associated with
      reductions in mortality and morbidity in children aged 6 months to 5 years.
      DESIGN: Systematic review and meta-analysis. Two reviewers independently assessed
      studies for inclusion. Data were double extracted; discrepancies were resolved by
      discussion. Meta-analyses were performed for mortality, illness, vision, and side
      effects. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL)
      in the Cochrane Library, Medline, Embase, Global Health, Latin American and
      Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index
      Medicus. Databases were searched to April 2010 without restriction by language or
      publication status. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials
      of synthetic oral vitamin A supplements in children aged 6 months to 5 years.
      Studies of children with current illness (such as diarrhoea, measles, and HIV),
      studies of children in hospital, and studies of food fortification or beta
      carotene were excluded. RESULTS: 43 trials with about 215,633 children were
      included. Seventeen trials including 194,483 participants reported a 24%
      reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69
      to 0.83). Seven trials reported a 28% reduction in mortality associated with
      diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a
      reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to
      0.67) and a reduced prevalence of vision problems, including night blindness
      (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials
      reported an increased risk of vomiting within the first 48 hours of
      supplementation (2.75, 1.81 to 4.19). CONCLUSIONS: Vitamin A supplementation is
      associated with large reductions in mortality, morbidity, and vision problems in
      a range of settings, and these results cannot be explained by bias. Further
      placebo controlled trials of vitamin A supplementation in children between 6 and
      59 months of age are not required. However, there is a need for further studies
      comparing different doses and delivery mechanisms (for example, fortification).
      Until other sources are available, vitamin A supplements should be given to all
      children at risk of deficiency, particularly in low and middle income countries.

PMID- 21868480
TI  - Improving child survival through vitamin A supplementation.

PMID- 21868481
TI  - Forward-backward masking of contrast patterns: the role of transients.
AB  - Graham and Wolfson have shown that, after adaptation to an array of Gabor
      patterns, observers discriminate poorly between spatially identical Gabor arrays
      in which the contrasts are symmetrically above and below the adapt contrast. Ten
      experiments are reported that show that the effect occurs in simple contrast
      discrimination tasks and examine its properties using a two-alternative spatial
      forced-choice paradigm. The experiments show that the effect is quite robust and
      manifests itself in several different experimental paradigms. It occurs with
      masks as short as 50 ms, but it disappears when an interval as short as 30 ms
      intervenes between the test patterns and the masks. It occurs at 4 and 8 c/deg.
      The decrease in discrimination for straddle contrasts is accompanied by an
      increase in discrimination for contrasts above the mask contrast. A model is
      presented that describes and predicts the results. The key idea of the model is
      that patterns which suddenly change contrast produce two responses in the visual
      system, a V-response that is a function of the absolute value of the difference
      between the test contrast and the mask contrast and an S-response that is an
      increasing function of contrast.

PMID- 21868482
TI  - Mesopic luminance assessed with minimum motion photometry.
AB  - We measured the relative contribution of rods and cones to luminance across a
      range of photopic, mesopic, and scotopic adaptation levels and at various retinal
      eccentricities. We isolated the luminance channel by setting motion-based
      luminance nulls (minimum motion photometry) using annular stimuli. Luminance
      nulls between differently colored stimuli require equality in a weighted sum of
      rod and cone excitations. The relative cone weight increases smoothly from the
      scotopic range, where rods dominate, to photopic levels, where rod influence
      becomes negligible. The change from rod to cone vision does not occur uniformly
      over the visual field. The more peripheral the stimulus location, the higher is
      the light level required for cones to participate strongly. The relative cone
      contribution can be described by a sigmoid function of intensity, with two
      parameters that each depend on the eccentricity and spatial frequency of the
      stimulus. One parameter determines the "meso-mesopic" luminance--the center of
      the mesopic range, at which rod and cone contributions are balanced. This
      increases with eccentricity, reflecting an increase in the meso-mesopic luminance
      from 0.04 scotopic cd/m(2) at 2 degrees  eccentricity to 0.44 scotopic cd/m(2) at
      18 degrees . The second parameter represents the slope of the log-log threshold
      versus-intensity curve (TVI curve) for rod vision. This parameter inversely
      scales the width of the mesopic range and increases only slightly with
      eccentricity (from 0.73 at 2 degrees  to 0.78 for vision at 18 degrees  off
      axis).

PMID- 21868483
TI  - Dual regulation of hepatitis C viral RNA by cellular RNAi requires partitioning
      of Ago2 to lipid droplets and P-bodies.
AB  - The antiviral role of RNA interference (RNAi) in humans remains to be better
      understood. In RNAi, Ago2 proteins and microRNAs (miRNAs) or small interfering
      RNAs (siRNAs) form endonucleolytically active complexes which down-regulate
      expression of target mRNAs. P-bodies, cytoplasmic centers of mRNA decay, are
      involved in these pathways. Evidence exists that hepatitis C virus (HCV) utilizes
      host cellular RNAi machinery, including miRNA-122, Ago1-4, and Dicer proteins for
      replication and viral genome translation in Huh7 cells by, so far, nebulous
      mechanisms. Conversely, synthetic siRNAs have been used to suppress HCV
      replication. Here, using a combination of biochemical, transfection, confocal
      imaging, and digital image analysis approaches, we reveal that replication of HCV
      RNA depends on recruitment of Ago2 and miRNA-122 to lipid droplets, while
      suppression of HCV RNA by siRNA and Ago2 involves interaction with P-bodies. Such
      partitioning of Ago2 proteins into different complexes and separate subcellular
      domains likely results in modulation of their activity by different reaction
      partners. We propose a model in which partitioning of host RNAi and viral factors
      into physically and functionally distinct subcellular compartments emerges as a
      mechanism regulating the dual interaction of cellular RNAi with HCV RNA.

PMID- 21868484
TI  - Valproic acid increases formation of reactive oxygen species and induces
      apoptosis in postimplantation embryos: a role for oxidative stress in valproic
      acid-induced neural tube defects.
AB  - Exposure to the anticonvulsant valproic acid (VPA) during the first trimester of
      pregnancy is associated with an increased risk of congenital malformations
      including heart defects, craniofacial abnormalities, skeletal and limb defects,
      and, most frequently, neural tube defects (NTDs). The mechanisms by which VPA
      induces teratogenic effects are not fully understood, although previous studies
      support a role for oxidative stress. To investigate the effects of VPA on early
      development, a whole-embryo culture model was used to evaluate the protective
      effects of antioxidants, measure intracellular reactive oxygen species (ROS)
      levels, and assess markers of oxidative damage and apoptosis. Furthermore, in
      vivo teratological evaluations of antioxidant protection were also completed. VPA
      (0.60 mM in embryo culture, 400 mg/kg in vivo) induced significant decreases in
      embryonic growth and increases in NTDs. Of the antioxidants tested, catalase
      provided partial protection against VPA-mediated reductions in morphological and
      developmental growth parameters in both whole-embryo culture and in vivo systems.
      VPA exposure resulted in an increase in ROS staining in the head region, as
      assessed by whole-mount staining with 5-(and-6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate. Markers of embryonic oxidative damage
      including 8-hydroxyguanosine, 4-hydroxynonenal adducts, and 3-nitrotyrosine were
      not affected by VPA treatment. Increased ROS levels were correlated with
      increased staining for apoptotic markers, as assessed by Western blotting and
      immunohistochemistry. Addition of catalase to the medium attenuated VPA-induced
      increases in ROS formation and apoptosis. These studies identify regions of the
      embryo susceptible to ROS and apoptosis induced by VPA, thus establishing a
      possible molecular pathway by which VPA exerts teratogenicity.

PMID- 21868485
TI  - Massive astrocyte destruction in neuromyelitis optica despite natalizumab
      therapy.
AB  - Auto-antibody mediated astrocyte injury is implicated as a primary event in
      neuromyelitis optica (NMO) by biomarker, post-mortem and experimental studies
      that differentiate the condition from multiple sclerosis. We describe the
      clinical, radiological and neuropathological features of a severe cerebral attack
      in a natalizumab-treated patient with relapsing myelitis and serum aquaporin-4
      antibodies. Our findings support autopsy evidence that abrupt astrocyte
      destruction precedes demyelination in NMO, and emphasize the importance of
      serological testing in patients with limited disease. Adherence to current NMO
      diagnostic criteria may delay treatment, or lead to inappropriate therapy with
      beta-interferon or natalizumab.

PMID- 21868486
TI  - Prediction of long-term disability in multiple sclerosis.
AB  - BACKGROUND: Little is known about the predictive value of neurophysiological
      measures for the long-term course of multiple sclerosis (MS). OBJECTIVE: To
      prospectively investigate whether combined visual (VEP) and motor evoked
      potentials (MEP) allow prediction of disability over 14 years. METHODS: A total
      of 30 patients with relapsing-remitting and secondary progressive MS were
      prospectively investigated with VEPs, MEPs and the Expanded Disability Status
      Scale (EDSS) at entry (T0) and after 6, 12 and 24 months, and with cranial MRI
      scans at entry (T2-weighted and gadolinium-enhanced T1-weighted images). EDSS was
      again assessed at year 14 (T4). The association between evoked potential (EP),
      magnetic resonance (MR) data and EDSS was measured using Spearman's rank
      correlation. Multivariable linear regression was performed to predict EDSS(T4) as
      a function of z-transformed EP-latencies(T0). The model was validated using a
      jack-knife procedure and the potential for improving it by inclusion of
      additional baseline variables was examined. RESULTS: EDSS values(T4) correlated
      with the sum of z-transformed EP-latencies(T0) (rho = 0.68, p < 0.0001), but not
      with MR-parameters(T0). EDSS(T4) as predicted by the formula EDSS(T4) = 4.194 +
      0.088 * z-score P100(T0) + 0.071 * z-score CMCT(UE, T0) correlated with the
      observed values (rho = 0.69, p < 0.0001). CONCLUSION: Combined EPs allow
      prediction of long-term disability in small groups of patients with MS. This may
      have implications for the choice of monitoring methods in clinical trials and for
      daily practice decisions.

PMID- 21868487
TI  - Clinical scales in progressive MS: predicting long-term disability.
AB  - BACKGROUND: To determine which short-term changes on clinical scales including
      the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole
      Peg test (9HPT) and Guy's Neurological Disability Scale (GNDS) are most
      predictive of long-term outcome of disability as rated by the EDSS in progressive
      multiple sclerosis (MS). METHODS: From a longitudinal database, all progressive
      patients, both primary (PP) and secondary (SP), were selected on the basis of at
      least two complete examinations being available within a time interval of 1-2
      years (short-term change). All patients who fulfilled the selection criteria were
      invited for a third visit after an interval of at least 3 years (long-term
      outcome). We used ordinal logistic regression to see which early changes were
      most predictive of the long-term EDSS. RESULTS: 181 patients fulfilled the
      selection criteria. Early change on EDSS and T25FW were the best predictors of
      long-term EDSS; both were significant predictors in a 'single predictor' model.
      Early EDSS change was a slightly stronger single predictor (R(2) 0.38, Wald
      chi(2) 42.65, p < 0.001) compared with early T25FW change (R(2) 0.27, Wald chi(2)
      12.35, p < 0.001). Adding early T25FW change to early EDSS change in a 'combined
      predictor' model improved prediction (p = 0.036). CONCLUSION: Both early change
      on EDSS and T25FW predict long-term EDSS with comparable strength. Early change
      on T25FW adds significant independent information and improves the prediction
      model with early EDSS change only. Therefore we support the use of early T25FW
      examinations in future clinical trials in progressive MS.

PMID- 21868488
TI  - The association of intrathecal immunoglobulin synthesis and cortical lesions
      predicts disease activity in clinically isolated syndrome and early relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: The intrathecal production of immunoglobulin (Ig) is a major
      biological feature of multiple sclerosis (MS), and immunopathological studies
      have suggested a primary role of the humoral immune response in causing
      irreversible brain damage. OBJECTIVE: To evaluate whether, in the early phases of
      MS, intrathecal Ig synthesis correlates with the presence of cortical lesions
      (CLs), and if their association could predict the clinical course of the disease.
      METHODS: Eighty-six patients presenting with symptoms and signs suggestive of MS
      underwent a diagnostic work-up that included magnetic resonance imaging and
      cerebrospinal fluid examination. The risk ratios (RR) for conversion to MS and
      for a new disease activity were calculated. RESULTS: Patients with clinically
      isolated syndromes (CIS) having CLs and intrathecal synthesis of Ig had the
      highest risk of conversion to MS (RR = 3.4; Wald 95% CI = 1.7-7.0, p < 0.001)
      whereas CIS patients without CLs and intrathecal synthesis of Ig had the lowest
      risk of conversion to MS (RR = 0.1, Wald 95% CI = 0.02-0.7, p < 0.001). The
      highest risk of having disease-related activity during the follow-up was observed
      in CIS and relapsing-remitting MS patients showing CLs and intrathecal Ig
      synthesis (RR = 2.1; Wald 95% CI = 1.5-3.1, p < 0.001) while the lowest in CIS
      and relapsing-remitting MS patients without CLs and intrathecal Ig synthesis (RR
      = 0.3; Wald 95% CI = 0.1-0.7, p < 0.001). CONCLUSION: We observed that the
      association of intrathecal immunoglobulin synthesis and CLs was highly predictive
      of an earlier CIS conversion to MS as well as of a higher disease activity.

PMID- 21868489
TI  - Altered gut microbiota composition in immune-impaired Nod2(-/-) mice.

PMID- 21868490
TI  - Bone marrow transplantation improves hepatic fibrosis in Abcb4-/- mice via Th1
      response and matrix metalloproteinase activity.
AB  - OBJECTIVE: Reports on the effects of bone marrow-derived cells on hepatic
      fibrosis are contradictory. Impaired fibrosis but increased inflammation has
      recently been demonstrated 10 weeks after bone marrow transplantation (BM-Tx) in
      Abcb4-/- mice. It is hypothesised that BM-Tx might have long-term therapeutic
      potential by altering the immunological and matrix remodelling processes leading
      to hepatic regeneration. METHODS: After lethal irradiation of recipient mice, BM
      cells from GFP+ donor mice (allogeneic Tx) or Abcb4-/- mice (syngeneic Tx) were
      transplanted via tail vein injection. Readouts were performed 2, 10 and 20 weeks
      after Tx. Liver integrity was assessed serologically and histologically.
      Surrogate markers for fibrogenesis, T helper (Th) response, inflammation, graft
      versus-host disease and fibrolysis were analysed by quantitative real-time PCR,
      zymography and immunohistology. RESULTS: 20 weeks after syngeneic and allogeneic
      BM-Tx, hepatic grading and staging were significantly improved. In contrast, 2
      weeks after BM-Tx inflammatory grading, expression of inflammatory cell markers
      and associated chemokines and their receptors were increased and subsequently
      declined. In parallel, CD8+/GFP+ donor-derived T cells infiltrated the liver 2
      weeks after BM-Tx. The Th1 cyokine interferon gamma was increased 2 and 10 weeks
      after BM-Tx whereas the Th2 associated interleukin 13 was not altered. The gene
      expression of matrix metalloproteinases MMP-2, MMP-7, MMP-9 and MMP-13 was
      transiently upregulated and MMP-9 protein remained elevated 20 weeks after BM-Tx
      with enhanced gelatinase activity located within the fibrotic areas. Neutrophils
      were identified as major sources of MMP-9. CONCLUSION: These results show that BM
      Tx causes an antifibrotic Th1 response combined with transient inflammatory
      effects and subsequently upregulated MMP activity. Antifibrotic Th polarisation
      and prolonged proteolytic activity, especially of MMP-9, might be responsible for
      long-term amelioration of hepatic fibrosis.

PMID- 21868491
TI  - Comparison between universal molecular screening for Lynch syndrome and revised
      Bethesda guidelines in a large population-based cohort of patients with
      colorectal cancer.
AB  - BACKGROUND: The selection of patients for genetic testing to rule out Lynch
      syndrome is currently based on fulfilment of at least one of the revised Bethesda
      criteria followed by mismatch repair (MMR) status analysis. A study was
      undertaken to compare the present approach with universal MMR study-based
      strategies to detect Lynch syndrome in a large series of patients with colorectal
      cancer (CRC). METHODS: 2093 patients with CRC from the EPICOLON I and II cohorts
      were included. Immunohistochemistry for MMR proteins and/or microsatellite
      instability (MSI) analysis was performed in tumour tissue. Germline MLH1 and MSH2
      mutation analysis was performed in patients whose tumours showed loss of MLH1 or
      MSH2 staining, respectively. MSH6 genetic testing was done in patients whose
      tumours showed lack of MSH6 expression or a combined lack of MSH2 and MSH6
      expression but did not have MSH2 mutations. PMS2 genetic testing was performed in
      patients showing isolated loss of PMS2 expression. In patients with MSI tumours
      and normal or not available MMR protein expression, all four MMR genes were
      studied. RESULTS: A total of 180 patients (8.6%) showed loss of expression of
      some of the MMR proteins and/or MSI. Four hundred and eighty-six patients (23.2%)
      met some of the revised Bethesda criteria. Of the 14 (0.7%) patients who had a
      MMR gene mutation, 12 fulfilled at least one of the revised Bethesda criteria and
      two (14.3%) did not. CONCLUSIONS: Routine molecular screening of patients with
      CRC for Lynch syndrome using immunohistochemistry or MSI has better sensitivity
      for detecting mutation carriers than the Bethesda guidelines.

PMID- 21868492
TI  - Visceral hypersensitivity in endometriosis: a new target for treatment?
AB  - OBJECTIVE: In women presenting to gynaecological clinics with lower abdominal
      pain, the cause is frequently attributed to endometriosis irrespective of whether
      it is found to be minimal or extensive at laparoscopy. Irritable bowel syndrome
      (IBS) is also common in this setting, and it was speculated that the visceral
      hypersensitivity associated with this condition might be amplifying the symptoms
      of endometriosis. METHODS: Visceral sensitivity to balloon distension, symptoms
      and psychological status were assessed following laparoscopy in 20 women with
      minimal to mild endometriosis, 20 with moderate to severe endometriosis, 20 with
      laparoscopy negative abdominal pain and 20 asymptomatic women undergoing
      laparoscopic sterilisation who acted as controls, and compared with 20 women with
      IBS. RESULTS: Compared with controls, patients with minimal to mild and moderate
      to severe endometriosis had a higher prevalence of symptoms consistent with IBS
      (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain
      thresholds (39.5 mm Hg (95% CI 36.0 to 43.0) vs 28.1 mm Hg (95% CI 24.5 to 31.6),
      p=0.001 and 28.8 mm Hg (95% CI 24.9 to 32.6), p=0.002) not explained by
      differences in rectal compliance. Patients with laparoscopy negative pain had
      symptoms and visceral sensitivity similar to patients with IBS. Controls
      undergoing laparoscopy had normal sensitivity, indicating that the laparoscopic
      procedure was not inducing hypersensitivity. CONCLUSION: Visceral
      hypersensitivity is extremely common in endometriosis and could be intensifying
      the pain. This finding might explain why mildly affected individuals often
      complain of severe symptoms out of proportion to the extent of their disease.
      This study has introduced a completely new concept into the understanding of pain
      in endometriosis and could open up new opportunities for treatment.

PMID- 21868493
TI  - Why do(n't) your partner's efforts at self-improvement make you happy? An
      implicit theories perspective.
AB  - People often try to improve their interpersonal skills to satisfy romantic
      partners. However, when and why a partner appreciates these efforts is an
      important but underaddressed question. The present research explored how people's
      theories that interpersonal abilities are either fixed entities or can be changed
      incrementally affect their responses to relationship partner's efforts at self
      improvement. Study 1 validated a new measure for these theories and showed that,
      compared to the former entity theorists, the latter incremental theorists were
      less likely to attribute recalled instances of partners' negative behaviors to
      dispositional causes and perceive these behaviors as fixed and stable. An
      experiment that induced these different implicit theories (Study 2) and a
      longitudinal study (Study 3) further demonstrated that perceptions of partners'
      self-improvement efforts led to greater increases in relationship security and
      quality among incremental than among entity theorists. How implicit theories may
      shape the interpersonal dynamics of self-improvement is discussed.

PMID- 21868494
TI  - Diversity is in the eye of the beholder: how concern for the in-group affects
      perceptions of racial diversity.
AB  - The reported studies suggest that concern for the in-group motivates Asian
      Americans and African Americans to define diversity specifically, that is, as
      entailing both minorities' numerical and hierarchical representation, while
      motivating White Americans to define diversity broadly, that is, as entailing
      either minorities' high numerical and/or hierarchical representation in an
      organization. Studies 2-4 directly assess if a concern for the in-group affects
      conceptions of diversity by measuring Black and White participants' racial
      identity centrality, an individual difference measure of the extent to which
      individuals define themselves according to race. These studies suggest that the
      tendency to conceive diversity in ways protective of the in-group is especially
      pronounced among individuals who identify strongly with their racial in-group.

PMID- 21868495
TI  - Presidential address: self-image and compassionate goals and construction of the
      social self: implications for social and personality psychology.
AB  - Interpersonal dynamics of self-esteem are explored. The author proposes that the
      desire to be seen as having positive qualities and avoid being seen as having
      dreaded qualities paradoxically leads to lowered self-esteem and lowered regard
      from others through its adverse effects on interpersonal relationships. The
      author also argues that the human capacity to transcend concerns with the images
      others hold of oneself, through caring about the well-being of other people,
      paradoxically leads to higher self-esteem and regard from others through its
      salutary effects on relationships. Data from two recent studies demonstrate these
      paradoxical effects and prompt questions about the nature of persons and
      situations, research methods, and the union between personality and social
      psychology. Accordingly, the author reflects more broadly on how people create
      their social situations, which in turn create the self, and what that means about
      the methods scholars use to understand social behavior.

PMID- 21868496
TI  - Valproic acid attenuates proteinuria and kidney injury.
AB  - Inhibitors of histone deacetylase (HDAC) have anti-inflammatory and antifibrotic
      effects in several organs and tissues, but their effect on the progression of
      renal disease is unknown. Here, we studied the effect of valproic acid in
      adriamycin-induced nephropathy in mice. Administration of valproic acid before
      kidney injury prevented the development of proteinuria and the onset of
      glomerulosclerosis. Even after postponing treatment until the peak of adriamycin
      induced proteinuria, valproic acid rapidly decreased the quantity of proteinuria
      and attenuated the progression of renal disease. Valproic acid abrogated the
      decrease in glomerular acetylation observed during adriamycin-induced
      nephropathy. Furthermore, valproic acid attenuated the significant upregulation
      of profibrotic and proinflammatory genes, the deposition of collagen, and the
      infiltration of macrophages into the kidney. Valproic acid decreased glomerular
      apoptosis and proliferation induced by adriamycin. Ultrastructural studies
      further supported the protective effect of valproic acid on podocytes in this
      model. Taken together, these data suggest that HDACs contribute to the
      pathogenesis of renal disease and that HDAC inhibitors may have therapeutic
      potential in CKD.

PMID- 21868497
TI  - Asymptomatic autoantibodies associate with future anti-glomerular basement
      membrane disease.
AB  - The pathophysiology of anti-glomerular basement membrane (anti-GBM) disease
      before clinical presentation is unknown. The presence of anti-GBM, anti
      proteinase 3 (PR3), and anti-myeloperoxidase (MPO) antibodies associate with the
      disease at the time of diagnosis, but little is known about the presence of these
      autoantibodies before diagnosis. We used serum samples from the Department of
      Defense Serum Repository to conduct a case-control study involving 30 patients
      diagnosed with anti-GBM disease and 30 healthy controls matched for the age,
      gender, race, and age of the serum samples. We analyzed a maximum of three
      samples from each subject: the most recent sample before diagnosis, the
      penultimate sample before diagnosis, and the oldest sample available; the average
      time between the most recent sample and diagnosis was 195 days (range, 4 to 1346
      days). Elevated anti-GBM levels (>=3 U/ml) were present in four patients, all
      less than 1 year before diagnosis but in no controls. Detectable anti-GBM
      antibody levels (>=1 U/ml but <3 U/ml) in a single serum sample before diagnosis
      were more frequent in cases than controls (70% versus 17%, P < 0.001). Only study
      patients had detectable anti-GBM levels in multiple samples before diagnosis (50%
      versus 0%, P < 0.001). Almost all patients had detectable anti-PR3 and/or anti
      MPO that preceded the onset of disease. Among patients with a clear antecedent
      antibody, anti-PR3 or anti-MPO always became detectable before the anti-GBM
      antibody. In summary, our data describe the subclinical formation of
      autoantibodies, which improves our understanding of the pathophysiology of anti
      GBM disease.

PMID- 21868498
TI  - Albuminuria and racial disparities in the risk for ESRD.
AB  - The causes of the increased risk for ESRD among African Americans are not
      completely understood. Here, we examined whether higher levels of urinary albumin
      excretion among African Americans contributes to this disparity. We analyzed data
      from 27,911 participants in the Reasons for Geographic and Racial Differences in
      Stroke (REGARDS) study who had urinary albumin-to-creatinine ratio (ACR) and
      estimated GFR (eGFR) measured at baseline. We identified incident cases of ESRD
      through linkage with the United States Renal Data System. At baseline, African
      Americans were less likely to have an eGFR <60 ml/min per 1.73 m(2) but more
      likely to have an ACR >= 30 mg/g. The incidence rates of ESRD among African
      Americans and whites were 204 and 58.6 cases per 100,000 person-years,
      respectively. After adjustment for age and gender, African Americans had a
      fourfold greater risk for developing ESRD (HR 4.0; 95% CI 2.8 to 5.9) compared
      with whites. Additional adjustment for either eGFR or ACR reduced the risk
      associated with African-American race to 2.3-fold (95% CI 1.5 to 3.3) or 1.8-fold
      (95% CI 1.2 to 2.7), respectively. Adjustment for both ACR and eGFR reduced the
      race-associated risk to 1.6-fold (95% CI 1.1 to 2.4). Finally, in a model that
      further adjusted for both eGFR and ACR, hypertension, diabetes, family income,
      and educational status, African-American race associated with a nonsignificant
      1.4-fold (95% CI 0.9 to 2.3) higher risk for ESRD. In conclusion, the increased
      prevalence of albuminuria may be an important contributor to the higher risk for
      ESRD experienced by African Americans.

PMID- 21868499
TI  - Obstructive sleep apnea and systemic hypertension: longitudinal study in the
      general population: the Vitoria Sleep Cohort.
AB  - RATIONALE: Obstructive sleep apnea and systemic hypertension (SH) are highly
      prevalent. Although their association has been suggested in cross-sectional
      studies, conflicting evidence has emerged from longitudinal studies. OBJECTIVES:
      To assess the association between obstructive sleep apnea and SH in the middle
      aged general population. METHODS: A total of 2,148 subjects were included in a
      longitudinal study of the Vitoria Sleep Cohort, a general population sample aged
      30-70 years. We analyzed data on office blood pressure, anthropometric measures,
      health history, and home polygraphy. Out of 1,557 subjects who completed the 7.5
      year follow-up, 377 were excluded for having SH at baseline. The odds ratios for
      the incidence of SH, according to the respiratory disturbance index (RDI) at
      baseline, were estimated in 1,180 subjects (526 men and 654 women) after
      adjustment for age; sex; body mass index; neck circumference; fitness level; and
      alcohol, tobacco, and coffee consumption. The RDI was divided into quartiles (0
      2.9, 3-6.9, 7-13.9, and >= 14), using the first quartile as reference.
      MEASUREMENTS AND MAIN RESULTS: The crude odds ratio for incident hypertension
      increased with higher RDI category with a dose-response effect (P < 0.001), but
      was not statistically significant after adjustment for age (P = 0.051).
      Adjustments for sex (P = 0.342), body mass index (P = 0.803), neck circumference
      (P = 0.885), and fitness level and alcohol, tobacco, and coffee consumption (P =
      0.708) further reduced the strength of the association between RDI and SH. No
      differences were observed between men and women. CONCLUSIONS: Our findings do not
      suggest an association between obstructive sleep apnea and the incidence of SH in
      the middle-aged general population. Long-term follow-up longitudinal studies are
      needed to better ascertain this association.

PMID- 21868500
TI  - Screening and prevention of venous thromboembolism in critically ill patients: a
      decision analysis and economic evaluation.
AB  - RATIONALE: Venous thromboembolism is difficult to diagnose in critically ill
      patients and may increase morbidity and mortality. OBJECTIVES: To evaluate the
      cost-effectiveness of strategies to reduce morbidity from venous thromboembolism
      in critically ill patients. METHODS: A Markov decision analytic model to compare
      weekly compression ultrasound screening (screening) plus investigation for
      clinically suspected deep vein thrombosis (DVT) (case finding) versus case
      finding alone; and a hypothetical program to increase adherence to DVT
      prevention. Probabilities were derived from a systematic review of venous
      thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010
      $US) were obtained from hospitals in Canada, Australia, and the United States,
      and the medical literature. Analyses were conducted from a societal perspective
      over a lifetime horizon. Outcomes included costs, quality-adjusted life-years
      (QALY), and incremental cost-effectiveness ratios. MEASUREMENTS AND MAIN RESULTS:
      In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening
      resulted in three fewer pulmonary emboli than case-finding alone but also two
      additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity
      analyses, screening cost less than $50,000 per QALY only if the probability of
      proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing
      adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16
      fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced
      thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs
      achieving increased adherence to best-practice venous thromboembolism prevention
      were cost-effective over a wide range of program costs and were robust in
      probabilistic sensitivity analyses. CONCLUSIONS: Appropriate prophylaxis provides
      better value in terms of costs and health gains than routine screening for DVT.
      Resources should be targeted at optimizing thromboprophylaxis.

PMID- 21868501
TI  - Intestinal injury and endotoxemia in children undergoing surgery for congenital
      heart disease.
AB  - RATIONALE: Children with congenital heart disease are at risk of gut barrier
      dysfunction and translocation of gut bacterial antigens into the bloodstream.
      This may contribute to inflammatory activation and organ dysfunction
      postoperatively. OBJECTIVES: To investigate the role of intestinal injury and
      endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital
      heart disease. METHODS: We analyzed blood levels of intestinal fatty acid binding
      protein and endotoxin (endotoxin activity assay) alongside global transcriptomic
      profiling and assays of monocyte endotoxin receptor expression in children
      undergoing surgery for congenital heart disease. MEASUREMENTS AND MAIN RESULTS:
      Levels of intestinal fatty acid binding protein and endotoxin were greater in
      children with duct-dependent cardiac lesions. Endotoxemia was associated with
      severity of vital organ dysfunction and intensive care stay. We identified
      activation of pathogen-sensing, antigen-processing, and immune-suppressing
      pathways at the genomic level postoperatively and down-regulation of pathogen
      sensing receptors on circulating immune cells. CONCLUSIONS: Children undergoing
      surgery for congenital heart disease are at increased risk of intestinal mucosal
      injury and endotoxemia. Endotoxin activity correlates with a number of outcome
      variables in this population, and may be used to guide the use of gut-protective
      strategies.

PMID- 21868502
TI  - The societal impact of single versus bilateral lung transplantation for chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Bilateral lung transplantation (BLT) improves survival compared with
      single lung transplantation (SLT) for some individuals with chronic obstructive
      pulmonary disease (COPD). However, it is unclear which strategy optimally uses
      this scarce societal resource. OBJECTIVES: To compare the effect of SLT versus
      BLT strategies for COPD on waitlist outcomes among the broader population of
      patients listed for lung transplantation. METHODS: We developed a Markov model to
      simulate the transplant waitlist using transplant registry data to define
      waitlist size, donor frequency, the risk of death awaiting transplant, and
      disease- and procedure-specific post-transplant survival. We then applied this
      model to 1,000 simulated patients and compared the number of patients under each
      strategy who received a transplant, the number who died before transplantation,
      and total post-transplant survival. MEASUREMENTS AND MAIN RESULTS: Under baseline
      assumptions, the SLT strategy resulted in more patients transplanted (809 vs.
      758) and fewer waitlist deaths (157 vs. 199). The strategies produced similar
      total post-transplant survival (SLT = 4,586 yr vs. BLT = 4,577 yr). In
      sensitivity analyses, SLT always maximized the number of patients transplanted.
      The strategy that maximized post-transplant survival depended on the relative
      survival benefit of BLT versus SLT among patients with COPD, donor interval, and
      waitlist size. CONCLUSIONS: In most circumstances, a policy of SLT for COPD
      improves access to organs for other potential recipients without significant
      reductions in total post-transplant survival. However, there may be substantial
      geographic variations in the effect of such a policy on the balance between these
      outcomes.

PMID- 21868503
TI  - Platelet-derived growth factor-producing CD4+ Foxp3+ regulatory T lymphocytes
      promote lung fibrosis.
AB  - RATIONALE: There is evidence that CD4(+) effector T lymphocytes (T eff)
      participate in the development of lung fibrosis, but the role of their CD4(+)
      regulatory T-cell (T reg) counterparts remains to be determined. OBJECTIVES: To
      elucidate the contribution of T reg cells in a mouse model of lung fibrosis
      induced by silica (SiO(2)) particles. METHODS: Lung T reg and T eff cells
      purified from SiO(2)-treated Foxp3-GFP transgenic mice were cocultured with naive
      lung fibroblasts or transferred to the lungs of healthy mice. DEREG mice, which
      express the diphtheria toxin receptor under the control of the foxp3 gene, were
      used to deplete T reg cells during fibrogenesis. MEASUREMENTS AND MAIN RESULTS:
      CD4(+) Foxp3(+) T reg cells were persistently recruited in the lungs in response
      to SiO(2). T reg accumulation paralleled the establishment of pulmonary
      immunosuppression and fibrosis. T reg cells highly expressed platelet-derived
      growth factor (PDGF)-B via a TGF-beta autocrine signaling pathway, directly
      stimulated fibroblast proliferation in vitro, and increased lung collagen
      deposition upon transfer in the lung of naive mice. The direct profibrotic
      effects of T reg cells were abolished by the inhibitor of the PDGF-B/TGF-beta
      signaling pathway, imatinib mesylate. Neutralization of T reg-immunosuppressive
      activity resulted in enhanced accumulation of T eff cells and IL-4-driven
      pulmonary fibrogenesis, further demonstrating that T reg cells control T eff cell
      functions during inflammatory fibrosis. CONCLUSIONS: Our study indicates that T
      reg cells contribute to lung fibrosis by stimulating fibroblasts through the
      secretion of PDGF-B in noninflammatory conditions and regulate detrimental T eff
      cell activities during inflammation-related fibrosis.

PMID- 21868504
TI  - A novel murine model of severe pulmonary arterial hypertension.
AB  - RATIONALE: The complex pathologies associated with severe pulmonary arterial
      hypertension (PAH) in humans have been a challenge to reproduce in mice due to
      the subtle phenotype displayed to PAH stimuli. OBJECTIVES: Here we aim to develop
      a novel murine model of PAH that recapitulates more of the pathologic processes,
      such as complex vascular remodeling and cardiac indices, that are not
      characteristic of alternative mouse models. METHODS: Inhibition of vascular
      endothelial growth factor receptor (VEGFR) with SU5416 combined with 3 weeks of
      chronic hypoxia was investigated. Hemodynamics, cardiac function, histological
      assessment of pulmonary vasculature, and molecular pathway analysis gauged the
      extent of PAH pathology development. MEASUREMENTS AND MAIN RESULTS: The
      combination of VEGFR inhibition with chronic hypoxia profoundly exacerbated all
      measures of PAH-like pathology when compared with hypoxia alone (> 45 mm Hg right
      ventricular pressure, > 0.35 right ventricular hypertrophy). The changes in
      pulmonary vascular remodeling in response to hypoxia were further enhanced on
      SU5416 treatment. Furthermore, hypoxia/SU5416 treatment steadily decreased
      cardiac output, indicating incipient heart failure. Molecular analysis showed a
      dysregulated transforming growth factor-beta/bone morphogenetic protein/Smad axis
      in SU5416- and/or hypoxia-treated mice as well as augmented induction of IL-6 and
      Hif-1alpha levels. These changes were observed in accordance with up-regulation
      of Tph1 and Pdgfr gene transcripts as well as a rise in platelet-rich serotonin.
      Biomarker analysis in response to VEGFR inhibition and/or hypoxia revealed
      distinct signatures that correlate with cytokine profiles of patients with
      idiopathic PAH. CONCLUSIONS: These data describe a novel murine model of PAH,
      which displays many of the hallmarks of the human disease, thus opening new
      avenues of investigation to better understand PAH pathophysiology.

PMID- 21868505
TI  - The response of children with asthma to ambient particulate is modified by
      tobacco smoke exposure.
AB  - RATIONALE: Ambient particulate matter concentrations have been positively
      associated with urinary leukotriene E(4) (LTE(4)) levels and albuterol usage in
      children with asthma but interactions with environmental tobacco smoke (ETS)
      exposure have not been demonstrated despite obvious exposure to both pollutants
      in an urban setting. OBJECTIVES: To assess the health effects of concurrent ETS
      and ambient particulate matter exposure in children with asthma. METHODS:
      Albuterol usage and LTE(4) levels were monitored in 82 urban schoolchildren with
      asthma over three consecutive fall to spring school periods. Concentrations of
      morning maximum ambient particulate matter <2.5 MUm in aerodynamic diameter
      (mmPM(2.5)) and urine cotinine levels were also measured daily. MEASUREMENTS AND
      MAIN RESULTS: Albuterol usage and LTE(4) were related to mmPM(2.5) concentrations
      on days when urine cotinine levels were low (<10 ng/ml/mg creatinine); on these
      days, mean albuterol usage and LTE(4) increased up to 5 or 6% per 10 MUg/m(3)
      increase in mmPM(2.5). In contrast, no significant relationship was observed when
      cotinine was high, although mean albuterol usage and LTE(4) levels were greater
      in this case. Model fits for LTE(4) levels as a function of mmPM(2.5)
      concentrations were improved when mmPM(2.5) concentrations were logged,
      suggesting a nonlinear dose-response relationship between particulate matter
      exposure concentrations and airway mediators of asthma, for which the
      relationship tends to flatten at higher concentrations. CONCLUSIONS: This study
      suggests that ETS modifies the acute effects of low-level ambient PM(2.5)
      exposure on childhood asthma. This negative interaction, the smaller effect of
      particulate matter exposure in children exposed to higher ETS, may be related to
      a nonlinear dose-response relationship between asthma mediators and particulate
      exposures.

PMID- 21868506
TI  - Sleep fragmentation induces cognitive deficits via nicotinamide adenine
      dinucleotide phosphate oxidase-dependent pathways in mouse.
AB  - RATIONALE: Sleep fragmentation (SF) is one of the major characteristics of sleep
      apnea, and has been implicated in its morbid consequences, which encompass
      excessive daytime sleepiness and neurocognitive impairments. We hypothesized that
      absence of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity
      is neuroprotective in SF-induced cognitive impairments. OBJECTIVES: To examine
      whether increased NADPH oxidase activity may play a role in SF-induced central
      nervous system dysfunction. METHODS: The effect of chronic SF during the sleep
      predominant period on sleep architecture, sleep latency, spatial memory, and
      oxidative stress parameters was assessed in mice lacking NADPH oxidase activity
      (gp91phox-(/Y)) and wild-type littermates. MEASUREMENTS AND MAIN RESULTS: SF for
      15 days was not associated with differences in sleep duration, sleep state
      distribution, or sleep latency in both gp91phox-(/Y) and control mice. However,
      on a standard place training task, gp91phox-(/Y) mice displayed normal learning
      and were protected from the spatial learning deficits observed in wild-type
      littermates exposed to SF. Moreover, anxiety levels were increased in wild-type
      mice exposed to SF, whereas no changes emerged in gp91phox-(/Y) mice.
      Additionally, wild-type mice, but not gp91phox-(/Y) mice, had significantly
      elevated NADPH oxidase gene expression and activity, and in malondialdehyde and 8
      oxo-2'-deoxyguanosine levels in cortical and hippocampal lysates after SF
      exposures. CONCLUSIONS: This work substantiates an important role for NADPH
      oxidase in hippocampal memory impairments induced by SF, modeling sleep apnea.
      Targeting NADPH oxidase, therefore, is expected to minimize hippocampal
      impairments from both intermittent hypoxia and SF associated with the disease.

PMID- 21868508
TI  - Gankyrin, a biomarker for epithelial carcinogenesis, is overexpressed in human
      oral cancer.
AB  - Little is known about the potential involvement of the oncoprotein gankyrin in
      human oral cancer progression. In this study, the levels of gankyrin mRNA and
      protein expression were assessed in human oral epithelial cell lines, at-risk
      normal oral tissues, premalignant oral lesions, and primary oral squamous cell
      carcinomas (OSCCs). MATERIALS AND METHODS: Biopsies included 6 oral epithelial
      cell lines, 32 OSCC specimens for qRT-PCR analysis, 27 OSCC specimens and 12
      premalignant oral lesions for immunohistochemical analysis. RESULTS: Gankyrin was
      overexpressed in all tested oral epithelial cell lines and the majority of OSCC
      specimens (32/32 (100%) and 21/27 (71%) at the mRNA and protein levels,
      respectively). Moreover, 6/12 of premalignant oral lesions overexpressed gankyrin
      protein. CONCLUSION: Gankyrin overexpression is a prevalent event in human oral
      cancer and occurs during the early stages of oral carcinogenesis, thus being a
      viable therapeutic or chemopreventive target in oral cancer.

PMID- 21868507
TI  - Tuberculosis drug development: ensuring people living with HIV are not left
      behind.
AB  - An unprecedented number of new tuberculosis (TB) medications are currently in
      development, and there will be great pressure to deploy these new drugs among all
      populations after their efficacy is demonstrated. People living with HIV
      experience a large burden of TB and have a particularly pressing need for TB
      treatments that are shorter and less toxic. In addition, all people living with
      HIV now require antiretroviral therapy during TB treatment. A roadmap of the
      research, programmatic, and regulatory considerations includes the following: (1)
      inclusion of people living with HIV early in clinical trials for treatment and
      prevention using new TB medications, (2) prioritization of key studies of HIV-TB
      drug interactions and interactions between new TB agents, and (3) optimization of
      clinical trial infrastructure, laboratory capacity, and drug susceptibility
      testing.

PMID- 21868509
TI  - Expression of selenium-containing proteins in human colon carcinoma tissue.
AB  - Selenium may be beneficial in reducing the risk of cancer incidence and mortality
      in many cancer types such as liver, prostate, colorectal and lung. However,
      despite the extensive recent research on selenium and selenium-containing
      proteins, there are still open questions concerning their expression in certain
      human cancer types, including colorectal carcinoma. Therefore, the expression
      level of the selenoproteins thioredoxin reductases 1 and 2 (TRXR-1 and TRXR-2)
      and glutathione peroxidases 1 and 4 (GPX1 and GPX4) in human colon carcinoma
      tissues was investigated. Up-regulation of TRXR-1 in the colon carcinoma
      specimens was found both in disease stage-dependent and independent analyses. No
      differences were found for TRXR-2 expression levels. GPX1 was up-regulated in
      carcinoma tissues at both the protein and mRNA levels. GPX4 was also up-regulated
      at the protein level, except for the samples derived from stage III patients. The
      expression of TRXR-1, GPX1 and GPX4, but not TRXR-2 is differently regulated in
      cancer as compared to healthy colonic tissue.

PMID- 21868510
TI  - Pomegranate extract induces cell cycle arrest and alters cellular phenotype of
      human pancreatic cancer cells.
AB  - BACKGROUND: Pomegranate extract (PE) is a standardized whole-fruit extract of
      pomegranate, a fruit with known anticancer properties. MATERIALS AND METHODS:
      PANC-1 and AsPC-1 human pancreatic cancer cells were used as in vitro models to
      test the effects of PE. RESULTS: PE treatment induced cell cycle arrest and
      inhibited cell proliferation in PANC-1 cells. PE treatment increased the
      proportion of cells lacking CD44 and CD24 expression, which are associated with
      increased tumor-initiating ability, demonstrating that PE altered cell phenotype.
      PE was more effective in inhibiting the proliferation of PANC-1 cells than the
      clinically used dose of paclitaxel. Similar results were obtained in the AsPC-1
      cell line. Individual pomegranate phytochemicals were only modestly effective in
      inhibiting cell proliferation, suggesting that unidentified phytochemicals are
      responsible for the inhibitory effect of PE. CONCLUSION: These data suggest that
      PE is a promising candidate for further preclinical testing for treatment of
      human pancreatic cancer.

PMID- 21868511
TI  - 6-Thioguanine inhibition of parathyroid hormone-related protein expression is
      mediated by GLI2.
AB  - BACKGROUND: Breast cancer cells frequently metastasize to bone, where they up
      regulate their expression of the transcription factor GLI2 and the downstream
      osteolytic factor parathyroid hormone-related protein (PTHrP). The guanosine
      nucleotide 6-thioguanine (6-TG) inhibits PTHrP expression and blocks osteolytic
      bone destruction in mice inoculated with bone metastatic cells; however, the
      mechanism by which 6-TG inhibits PTHrP remains unclear. We hypothesized that 6-TG
      inhibition of PTHrP is mediated through GLI2 signaling. MATERIALS AND METHODS:
      Human MDA-MB-231 breast cancer cells and RWGT2 squamous-cell lung carcinoma cells
      were treated with 100 MUM 6-TG and examined for GLI2 mRNA expression and
      stability by Q-PCR, promoter activity by luciferase assay, and protein expression
      by Western blot. RESULTS: 6-TG significantly blocked GLI2 mRNA and protein
      expression, but did not affect stability. Additionally, 6-TG directly inhibited
      GLI2 promoter activity, and when cells were transfected with constitutively
      expressed GLI2, the inhibitory effect of 6-TG on PTHrP expression was abolished.
      CONCLUSION: Taken together, these data indicate that 6-TG regulates PTHrP in part
      through GLI2 transcription, and therefore the clinical use of 6-TG or other
      guanosine nucleotides may be a viable therapeutic option in tumor types
      expressing elevated levels of GLI proteins.

PMID- 21868512
TI  - The mTOR inhibitor RAD001 sensitizes tumor cells to the cytotoxic effect of
      carboplatin in breast cancer in vitro.
AB  - AIM: The phosphatidylinositol 3-kinase (PI3K)/protein kinase B(AKT)/mammalian
      target of rapamycin (mTOR) signaling pathway is aberrantly activated in many
      types of cancer, including breast cancer. It is recognized that breast cancer
      cells develop resistance to a variety of standard therapies through the
      activation of this pathway. We hypothesized that targeting this signaling by the
      mTOR inhibitor RAD001 may potentiate the cytotoxicity of a conventional
      chemotherapeutic drug, carboplatin, and enhance the treatment efficacy for breast
      cancer. MATERIALS AND METHODS: Cell proliferation was measured with 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; cell apoptosis
      with enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used for the
      analysis of cell cycle distribution and mitochondrial membrane function. Gene
      expression at the protein level was determined by Western blot. RESULTS: MTOR
      inhibitor RAD001 enhanced the sensitivity of breast cancer cells to carboplatin.
      RAD001 in combination with carboplatin resulted in synergistic inhibition of cell
      proliferation and caspase-independent apoptosis in these cells. Moreover, in MCF
      7 and BT-474 cells, synergistic effects of this combination on G2/M cell cycle
      arrest and regulation of different molecules responsible for cell cycle
      transition and apoptosis were observed. The p53 pathway was involved in the
      synergism of RAD001 and carboplatin on breast cancer cell proliferation and
      apoptosis, since the synergistic effect was demonstrated in all tested breast
      cancer cell lines with wild-type p53 and the use of p53 inhibitor partially
      antagonized the effect of RAD001 and carboplatin on p53 and p21 expression, as
      well as their inhibitory effect on cell proliferation. However, a synergistic
      effect of the combination of the two drugs on cell proliferation was observed in
      two p53-mutated cell lines with high AKT expression, suggesting that an
      alternative mechanism underlying the observed synergism exists. CONCLUSION: Our
      results suggest that the combination of RAD001 and carboplatin is a promising
      treatment approach for breast cancer. On the basis of these results, we have
      initiated a phase I/II clinical trial with the combination of carboplatin and
      RAD001 in patients with metastatic breast cancer.

PMID- 21868513
TI  - Histone deacetylase inhibitors reverse CpG methylation by regulating DNMT1
      through ERK signaling.
AB  - Methylation of CpG repeats in the upstream/promoter regions of genes is an
      established mechanism of gene silencing in many cell types. DNA methylation
      results in the recruitment of histone deacetylases (HDACs) to promoter regions,
      thereby repressing expression of genes. General inhibitors of class I and II
      HDACs (HDACi), such as sodium butyrate and suberoylanilide hydroxamic acid,
      suppress the growth of prostate cancer cells in vitro and in vivo. In this study,
      we investigated the mechanism of re-expression of silenced cell cycle inhibitors
      and retinoic acid receptor B2 (RARB2). HDACi inhibited cell cycle progression,
      and reversed promoter methylation and silencing of three tumor suppressor genes:
      RARB2 and the cell cycle regulating cyclin-dependent kinase inhibitors p16 and
      p21. HDACi repressed MAP kinase I (ERK) activation and down-regulated DNA
      (cytosine-5-)-methyltransferase 1 (DNMT1) levels. Direct inhibition of ERK
      activity similarly decreased DNMT1 protein levels and reversed the basal
      hypermethylation of the promoters and silencing of the RARB2, p21 and p16 tumor
      suppressor genes. Suppression of DNMT1 level by siRNA also reversed methylation
      of these tumor suppressor genes with similar kinetics. Collectively, these data
      demonstrate that HDACi, by inhibiting ERK activity, regulate DNMT1 and ultimately
      DNA methylation. These results demonstrate that HDACs regulate gene methylation,
      in addition to the established and reciprocal ability of CpG methylation to
      recruit HDACs to repress transcription.

PMID- 21868514
TI  - Protein-bound polysaccharide-K (PSK) induces apoptosis and inhibits proliferation
      of promyelomonocytic leukemia HL-60 cells.
AB  - Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor
      (CM101), and is clinically used in combination therapy for gastrointestinal
      cancer and small cell lung carcinoma. PSK is a biological response modifier
      (BRM), and its mechanism of action is partly mediated, by modulating host immune
      systems, such as the activation of immune effector cells and the neutralization
      of transforming growth factor-beta (TGFbeta) activity. Direct inhibition of tumor
      cell proliferation has been reported as another mechanism, but how PSK induces
      such an effect remains to be elucidated. Here, the anti-proliferative activity of
      PSK was examined using seven different human malignant cell lines (WiDr, HT29,
      SW480, KATOIII, AGS, HL60 and U937), and PSK was found to inhibit the
      proliferation of HL-60 cells most profoundly. Therefore, HL-60 cells were used to
      clarify the mechanism of anti-proliferative activity. Caspase-3 activation
      followed by apoptosis are involved at least in part in the PSK-induced anti
      proliferative activity against HL-60 cells.

PMID- 21868515
TI  - Clioquinol suppresses cyclin D1 gene expression through transcriptional and post
      transcriptional mechanisms.
AB  - Clioquinol, a metal-binding compound, has been shown to have anticancer activity
      in in vitro and in vivo model systems. This study investigated the effects of
      clioquinol on cyclin D1 gene expression in breast cancer cells. Treatment with
      clioquinol significantly reduced cyclin D1 protein levels in a concentration
      dependent manner, effects being more pronounced in the presence of zinc.
      Clioquinol reduced cyclin D1 mRNA contents in cells that had been pre-treated
      with actinomycin D, indicating that this compound alters cyclin D1 mRNA
      stability, an event associated with post-transcriptional regulation. Using a
      cyclin D1 3'-UTR reporter construct (CCND1-3'-UTR), we confirmed that this 3'-UTR
      mediates the inhibitory action of clioquinol, likely through miR-302C. This study
      demonstrates for the first time that clioquinol targets post-transcriptional
      steps of cyclin D1 gene expression in cancer cells, adding new insight into our
      understanding of its mechanisms of anticancer action.

PMID- 21868516
TI  - Prognostic relevance of disseminated tumor cells in the bone marrow of patients
      with primary breast cancer--results of a standardized follow-up.
AB  - BACKGROUND: The prognostic significance of disseminated tumor cells from bone
      marrow (BM-DTCs) of breast cancer patients has been demonstrated previously. In
      this study, data of a standardized long term follow-up of 829 patients with
      examination of BM-DTCs at primary diagnosis are presented. PATIENTS AND METHODS:
      BM aspiration and immunocytochemical examination of DTCs was performed according
      to a standardized protocol. Follow-up data of all patients were adjusted with the
      cancer registries of southern Bavaria. RESULTS: A total of 268 patients (32%) had
      BM-DTCs with a median of 2 (1-1223)/2 x 106 cells. Positive BM findings
      correlated with tumor size (p=0.032), but not with other histopathological
      parameters. After a median follow-up of 73 months, BM-DTCs were highly relevant
      for the development of distant metastases (p=0.006) and, beneath standard
      histological parameters, reduced overall survival (p=0.038). CONCLUSION: These
      results confirm the prognostic relevance of the detection of BM-DTCs. Newer
      methods, such as detection of circulating tumor cells in blood, will have to
      demonstrate comparable prognostic information in the future.

PMID- 21868517
TI  - Modulation of cisplatin cytotoxicity due to its combination with bortezomib and
      the nature of its administration.
AB  - The widely used anticancer drug cisplatin (CS) is believed to cross the cell
      membrane by passive diffusion, carrier-mediated transport and pinocytosis. One
      carrier involved in the transport of CS into the cell is the copper transporter
      CTR1. However, CS is found to trigger the down-regulation of CTR1 and its
      proteasomal degradation. The proteasome inhibitor bortezomib (Bort) has been
      reported to block CS-induced down-regulation of CTR1 so that in the presence of
      Bort, the cellular uptake of CS may be increased. Increased platinum accumulation
      may result in increased platinum-DNA binding so that CS in combination with Bort
      may produce pronounced cell kill. In this study, synergism in activity from the
      sequenced combination of CS and Bort in human ovarian A2780, A2780(cisR) and
      A2780(ZD0473R) cancer cell lines was studied. We also investigated the effect on
      cell kill due to the administration of CS in two aliquots with a time gap.
      Addition of Bort 2 h before CS was found to produce greater cell kill than the
      converse and the bolus, especially in the resistant A2780(cisR) and
      A2780(ZD0473R) cell lines, in line with increased platinum accumulation and
      platinum-DNA binding levels. Thus, the prevention of CTR1 degradation by Bort may
      play a significant role, especially in the resistant cell lines. Administration
      of CS in two aliquots with a time gap was also found to maximise the cell kill in
      the ovarian cancer cell lines. If such findings are found to be true in vivo, the
      results may be significant clinically.

PMID- 21868518
TI  - Prognostic significance of thymidylate synthase expression in the adjuvant
      chemotherapy after resection for pulmonary metastases from colorectal cancer.
AB  - BACKGROUND: Recent studies have discussed on the prognostic value of thymidylate
      synthase (TS) assessment in metastases of colorectal cancer (CRC). The aim of
      this study was to evaluate the prognostic significance of molecular biomarkers
      including TS expression, after pulmonary metastasectomy followed by 5
      fluorouracil-based adjuvant chemotherapy. PATIENTS AND METHODS: A total of 80
      patients who underwent metastasectomy for pulmonary recurrence from CRC were
      included in this study. Tumor sections were stained by immunohistochemistry for
      TS, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase
      (DPD), excision repair cross-complementation group 1 (ERCC1), breast cancer
      susceptibility gene 1 (BRCA1), vascular endothelial growth factor (VEGF),
      microvessel density (MVD) assessed by CD34 and p53. RESULTS: Survival after
      pulmonary metastasectomy was significantly longer in patients treated by adjuvant
      chemotherapy than those without adjuvant therapy. TS, OPRT, ERCC1, BRCA1 and CD34
      expression was significantly associated with better outcome from the use of
      adjuvant chemotherapy. CONCLUSION: Expression level of TS, OPRT, ERCC1, BRCA1 and
      MVD in resected colorectal lung metastases may play an important role for
      predicting outcome after 5-fluorouracil-based adjuvant therapy.

PMID- 21868519
TI  - In vitro and in vivo anticancer activity of (+)-spongistatin 1.
AB  - The marine natural product (+)-spongistatin 1 is an extremely potent growth
      inhibitory agent having activity against a wide variety of cancer cell lines,
      while exhibiting low cytotoxicity against quiescent human fibroblasts. Consistent
      with a microtubule-targeting mechanism of action, (+)-spongistatin 1 causes
      mitotic arrest in DU145 human prostate cancer cells. More importantly, (+)
      spongistatin 1 exhibits significant in vivo antitumor activity in the LOX-IMVI
      human melanoma xenograft model. (+)-Spongistatin 1 is, thus, an important class
      of microtubule targeting anticancer agent that warrants further investigation.

PMID- 21868520
TI  - Interaction of dacarbazine and imexon, in vitro and in vivo, in human A375
      melanoma cells.
AB  - AIM: We evaluated mechanisms of interaction between the alkyating agent
      dacarbazine (DTIC) and the pro-oxidant, imexon, in the human A375 melanoma cell
      line. MATERIALS AND METHODS: The effect of DTIC and imexon, alone and in
      combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake,
      cellular thiol content (HPLC), and DNA strand breaks (Comet assay).
      Pharmacokinetic and antitumor effects were evaluated in mice. RESULTS: Growth
      inhibition in vitro was additive with the two drugs. There was no effect on drug
      uptake or on the number of DNA strand breaks. There was a >75% reduction in
      cellular glutathione and cysteine with imexon but not DTIC. Co-administration of
      the two drugs in mice caused an increase in the area under the curve of both
      drugs, but the combination was not effective in reducing human A375 melanoma
      tumors in vivo. CONCLUSION: Imexon and dacarbazine show additive effects in vitro
      but not in vivo in human A375 melanoma cells.

PMID- 21868521
TI  - Acquired drug resistance to vascular endothelial growth factor receptor 2
      tyrosine kinase inhibitor in human vascular endothelial cells.
AB  - Acquired resistance to antiangiogenic drugs has emerged as a potentially
      important issue in clinical settings; however, the underlying molecular and
      cellular mechanism of resistance to vascular endothelial growth factor receptor 2
      (VEGFR2) tyrosine kinase inhibitor (TKI) remains largely unclear. We evaluated
      the cellular characteristics of human umbilical vein endothelial cell (HUVEC)
      clones, which are resistant to VEGFR2-TKI (Ki8751) to elucidate this mechanism of
      resistance to antiangiogenic drugs. Resistant HUVEC clones were 10-fold more
      resistant to VEGFR2-TKI than the parental cells and they exhibited an almost
      complete absence of VEGF-mediated cellular proliferation. The mRNA expression
      analysis revealed that expression of VEGFR1, VEGFR2 and VEGFR3 was lower in
      resistant clones, while that of several angiogenic ligands was increased. The
      protein expression of VEGFR2 was markedly down-regulated in two (R5 and R6 clone)
      out of five resistant clones. Focusing on the R5 clone, VEGF stimulation did not
      increase the phosphorylation of VEGFR2 or the dimerization of VEGFR2. The
      inhibition of phospho-AKT by VEGFR2-TKI was also weakened more than 10-fold in
      the R5 clone. Finally, a microarray analysis revealed that some angiogenesis
      associated, and some angiogenesis-specific genes, including platelet endothelial
      cell adhesion molecule 1 (PECAM1)/CD31, homeobox A9 (HOXA9), and endothelial cell
      specific molecule 1 (ESM1), were remarkably down-regulated in all the resistant
      clones compared with the parental cells. HUVEC clones resistant to VEGFR2-TKI
      exhibited down-regulation of VEGFR2, a decreased signal response to VEGF
      stimulation, and the loss of vascular endothelial markers. These results strongly
      suggest that an escape from VEGFR2 signaling-dependency is one of the cellular
      mechanisms of resistance to VEGFR2-TKI in vascular endothelial cells.

PMID- 21868522
TI  - SDF1beta expression in renal cell carcinoma correlates with grading and
      infiltration by CD8+ T-cells.
AB  - For several tumor entities, a significant correlation between the chemokine
      stromal cell-derived factor 1 (SDF1) and its receptor C-X-C chemokine receptor
      type 4 (CXCR4), metastasis and tumor proliferation, as well as prognosis, has
      been described. In this study, a series of 105 renal cell carcinoma patients were
      analyzed in terms of expression of SDF1alpha and SDF1beta and infiltration by
      CD4+ and CD8+ T-cells and the data correlated with TNM category, grading and
      survival. While the splice variant SDF1alpha had no impact on tumor grading, T
      cell invasion or overall survival, expression of SDF1beta showed a significant
      correlation with tumor grading and also suggested a correlation with metastasis,
      as well as CD8+ T-cell invasion. These results indicate a potential T-cell
      mediated antitumor response induced by SDF1beta up-regulation. Therefore
      targeting the SDF1beta-CXCR4 signaling pathway may be a promising means for new
      therapeutic strategies in advanced tumor stages.

PMID- 21868523
TI  - Activation of the Wnt/beta-catenin signaling pathway during oral carcinogenesis
      process is not influenced by the absence of galectin-3 in mice.
AB  - BACKGROUND/AIM: Galectin-3 has been associated with activated Wnt pathway,
      translocating beta-catenin into the nucleus. However, it is still unknown whether
      this lectin drives the Wnt signaling activation in lesions from galectin-3
      deficient (Gal3-/-) mice. The purpose was to study beta-catenin expression in
      tongue lesions from Gal3-/- and wild-type (Gal3+/+) mice and the status of Wnt
      signaling. MATERIALS AND METHODS: Twenty Gal3-/- and Gal3+/+ male mice were
      challenged with 4-nitroquinolin-1-oxide and killed at week 16 and 32. Tongues
      were processed and stained with H&E to detect dysplasias and carcinomas. An
      imunohistochemical assay was performed to evaluate beta-catenin expression.
      RESULTS: Carcinomas were more evident in Gal3+/+ than Gal3-/- mice (55.5% vs.
      28.5%, respectively; p>0.05). Elevated expression of non-membranous beta-catenin
      was observed in dysplasias and carcinomas from both groups (p>0.05). CONCLUSION:
      Absence of galectin-3 does not interfere in the pattern of beta-catenin
      expression and therefore in the mediation of the Wnt signaling pathway.

PMID- 21868524
TI  - Anti-MDR1 siRNA restores chemosensitivity in chemoresistant breast carcinoma and
      osteosarcoma cell lines.
AB  - BACKGROUND: Reversion of chemoresistance by inhibition of P-glycoprotein (P-gp)
      expression may overcome the chemoresistance observed in many cancer types and may
      allow for improved therapeutic ratio. We investigated whether siRNA specific for
      ABCB1 (MDR1) mRNA might restore sensitivity to chemotherapy in tumor cell lines
      known to overexpress the MDR1 gene. MATERIALS AND METHODS: MDR1-expressing tumor
      cell lines were transiently transfected with anti-MDR1 silencing RNA (siRNA)
      before exposure to doxorubicin or methotrexate. The capacity of siRNA to reduce
      cell proliferation and increase the IC50 of the tested chemotherapies was
      investigated. RESULTS: siRNA down-regulated MDR1 mRNA expression by 50% in breast
      carcinoma and osteosarcoma cell lines, and significantly inhibited tumor cell
      proliferation up to 90% (p<0.01), when co-administered with doxorubicin or
      methotrexate, despite the known chemoresistance of the cell lines. siRNAs reduced
      the IC50 of doxorubicin and methotrexate by more than 10-fold (p<0.01).
      CONCLUSION: These results suggest the potential clinical application of anti-MDR1
      siRNA to restore chemosensitivity and possibly improve the therapeutic ratio of
      these cytotoxic drugs.

PMID- 21868525
TI  - Gallic acid induces G0/G1 phase arrest and apoptosis in human leukemia HL-60
      cells through inhibiting cyclin D and E, and activating mitochondria-dependent
      pathway.
AB  - Gallic acid (GA) induces apoptosis in different types of cancer cell lines. In
      this study, we investigate the apoptotic effects induced by GA in human
      promyelocytic leukemia HL-60 cells, and clarify the underlying mechanism. Our
      results showed that GA reduced the viability of HL-60 cells in a dose- and time
      dependent manner. GA led to G(0)/G(1) phase arrest in HL-60 cells through
      promoting p21 and p27 and inhibiting the levels of cyclin D and cyclin E. GA
      caused DNA damage and fragmentation in HL-60 cells as assayed using DAPI staining
      and Comet assay. Flow cytometric analysis revealed that GA increased Ca(2+)
      levels and reduced the mitochondrial membrane potential (DeltaPsi(m)) in HL-60
      cells. Apoptotic protein expressions were determined by Western blotting. The
      results indicated that GA-mediated apoptosis of HL-60 cells mainly depended on
      mitochondrial pathway, by promoting the release of cytochrome c, apoptosis
      inducing factor (AIF) and endonuclease G (Endo G) and by up-regulating the
      protein expression of Bcl-2-associated X protein (BAX), caspase-4, caspase-9 and
      caspase-3. In addition, GA also activated the death receptor-dependent pathway by
      enhancing the protein expressions of fatty acid synthase (FAS), FAS ligand
      (FASL), caspase-8 and BCL-2 interacting domain (BID). We determined the mRNA
      expression of the gene levels of these proteins by real-time PCR. The results
      showed that GA-mediated apoptosis of HL-60 cells mainly depended on up-regulation
      of the mRNA of caspase-8, caspase-9, caspase-3, AIF and Endo G. In conclusion, GA
      induced apoptosis occurs through the death receptor and mitochondria-mediated
      pathways. The evaluation of GA as a potential therapeutic agent for treatment of
      leukemia seems warranted.

PMID- 21868526
TI  - Correlation between expression of metallothionein and expression of Ki-67 and MCM
      2 proliferation markers in non-small cell lung cancer.
AB  - BACKGROUND: Metallothioneins (MTs) are low molecular weight proteins present both
      in normal and neoplastic cells. They protect cells from the effects of heavy
      metals and from damage induced by free radicals. MT bind heavy metals, exert an
      anti-apoptotic effect and stimulate proliferation of neoplastic cells. The role
      of MTs in carcinogenesis has not been fully clarified yet. This study aimed at
      the evaluation of the intensity of metallothionein (MT-I/II) expression in
      various histological types of non-small cell lung cancer (NSCLC) and correlation
      of the expression intensity with clinical/pathological parameters and Ki-67 and
      minichromosome maintaince protein 2 (MCM-2) proliferation markers. PATIENTS AND
      METHODS: The studies were performed on archival material, originating from 145
      patients, 105 men and 40 women (65 adenocarcinomas, 67 squamous cell carcinomas,
      13 large cell carcinomas). RESULTS: A positive correlation was noted between
      expression of MT-I/II and expressions of Ki-67 (r=0.1863, p=0.0248) and MCM-2
      (r=0.1766, p=0.0336) in NSCLC overall. The most pronounced expression of MT-I/II
      was noted in the large cell carcinomas. The expression of MT-I/II was
      significantly lower in the adenocarcinomas than in the squamous cell carcinomas
      (p=0.0028) and large cell carcinomas (p=0.0485). The expression of MT-I/II showed
      no differences related to individual degrees of NSCLC malignancy. Univariate
      analysis demonstrated no significant differences in overall survival related to
      the expression intensity of MT-I/II, Ki-67 or MCM-2, but the survival of the
      patients with high expression of MT-I/II and Ki-67 in the neoplastic cells, as
      compared to low expression of MT-I/II and Ki-67, was shorter (the difference
      approached statistical significance, p=0.067). CONCLUSION: MT-I/II expression is
      evident in proliferating NSCLC neoplastic cells, pointing to the prognostic
      importance of parallel expression of MT-I/II and Ki-67.

PMID- 21868527
TI  - Evaluation of anticancer activities of benzo[c]phenanthridine alkaloid
      sanguinarine in oral squamous cell carcinoma cell line.
AB  - While the effects of benzo[c]phenanthridine alkaloids (QBA), known mainly as
      sanguinarine and chelerythrine, on the inhibition of some kinds of cancer cell
      proliferation have been established, the effect on oral squamous cell is not
      known. Here, the antitumor activity of sanguinarine was demonstrated using in
      vitro assay systems in SAS, a human oral squamous cell carcinoma (OSCC) cell
      line. The anti-proliferative and -invasive effects were confirmed with IC50
      values in the concentration range of 0.75-1.0 MUM by MTT assay and invasive
      assay, respectively. Sanguinarine was also able to suppress cell anchorage
      independent growth, whereas it did not affect the cells' adhering capabilities.
      Finally, sanguinarine induced apoptotic cell death by activating caspase and
      altering the Bcl-2/Bax ratio. Taken together, these results indicate that
      sanguinarine is a potential inhibitor of tumorigenesis and suggest that it may be
      valuable in the development of new anticancer drugs for the treatment of OSCC.

PMID- 21868528
TI  - Interaction of radiation and pemetrexed on a human malignant mesothelioma cell
      line in vitro.
AB  - PURPOSE: To investigate the interaction of the cytotoxic activity of the
      combination of pemetrexed and radiation in a human mesothelioma cell line.
      MATERIALS AND METHODS: The toxic effects of treatment with radiation and/or
      pemetrexed (PEM) on NCI-H28 cells were assessed by clonogenic assay. TUNEL/DAPI
      staining was used to measure the apoptosis index (AI). Thymidylate synthase (TS)
      protein expression was measured by Western blotting. RESULTS: The D0 value of the
      combination treatment was lower than that for radiation, indicating its addition
      resulted in the synergistic effects with radiation. An increase in AI was
      observed with the combination compared with that observed after PEM alone.
      Radiation induced a time-dependent decrease in TS expression. Increased TS
      expression was observed after PEM, but the combination treatment decreased TS
      expression. CONCLUSION: Treatment with pemetrexed in combination with radiation
      has a supra-additive effect, partially due to the synergistic induction of
      apoptosis, which may be due to TS suppression, by the irradiation enhancing the
      effect of pemetrexed.

PMID- 21868529
TI  - Antitumor therapeutic effects of cytosine deaminase and interferon-beta against
      endometrial cancer cells using genetically engineered stem cells in vitro.
AB  - Interest in gene therapy has recently increased; in particular, gene-directed
      enzyme/prodrug therapies have been found to be more advantageous compared to
      radiotherapy and/or chemotherapy. One of these, a cytosine deaminase (CD)/5
      fluorocytosine (5-FC) system, is known to induce apoptosis by converting 5-FC, a
      prodrug, to its metabolically active form, 5-fluorouracil. The present study was
      designed to examine the migratory and therapeutic effects of engineered human
      stem cell lines against endometrial cancer using this strategy. The parental stem
      cells, HB1.F3, were modified to express Escherichia coli CD or human interferon
      beta (IFN-beta), thereby producing HB1.F3.CD and HB1.F3.CD.IFN-beta cells,
      respectively. The parental and engineered stem cells (HB1.F3, HB1.F3.CD, and
      HB1.F3.CD.IFN-beta) significantly migrated toward endometrial cancer cells
      (Ishikawa) more than primary bovine fibroblasts (bovine FB). In addition,
      important chemoattractant factors, including stem cell factor (SCF), vescular
      endothelial growth factor, vescular endothelial growth factor receptor 2, C-X-C
      chemokine receptor type 4, and c-KIT, involved in the tumor-tropic ability of
      stem cells were expressed in Ishikawa cells. In using a co-culture system and MTT
      assay, reduced viability of endometrial cancer cells was observed in the presence
      of HB1.F3.CD and HB1.F3.CD.IFN-beta cells with prodrug 5-FC. Taken together,
      these results suggest that gene therapy employing genetically modified stem cells
      expressing CD and IFN-beta may be effective for treating endometrial cancer.

PMID- 21868530
TI  - Determination of clofarabine triphosphate concentrations in leukemia cells using
      sensitive, isocratic high-performance liquid chromatography.
AB  - BACKGROUND/AIM: An active metabolite of the anti-leukemia agent clofarabine (Cl-F
      ara-A) is an intracellular triphosphate form, Cl-F-ara-ATP. Monitoring this
      active form could provide crucial information for optimizing treatment regimens
      based on Cl-F-ara-A. A simple, isocratic HPLC method was developed. MATERIALS AND
      METHODS: Samples (500 MUl) from leukemic cells were loaded onto an anion-exchange
      column and eluted with a phosphate-acetonitrile buffer (flow rate: 0.7 ml/min) at
      ambient temperature. The Cl-F-ara-ATP concentration was determined by measuring
      absorbance at 254 nm. RESULTS: The standard curve was linear, with minimal within
      day and inter-day variability. Recovery was excellent; low and high quantitation
      limits were 10 pmol and 5,000 pmol, respectively. Cl-F-ara-ATP eluted
      independently of ATP, GTP, UTP, and CTP. Production of Cl-F-ara-ATP was
      successfully measured in cultured leukemia HL-60 cells treated in vitro with Cl-F
      ara-A. CONCLUSION: This method is simple, sensitive and applicable for
      determination of the Cl-F-ara-ATP content of biological materials.

PMID- 21868531
TI  - H-ras up-regulates expression of BNIP3.
AB  - BACKGROUND: Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) is
      a key regulator of cell death/autophagy and can act as an effector of a necrosis
      like, atypical death program. It was implicated in execution of cell death
      induced by cluster of differentiation 47 (CD47). Despite the postulated role of
      BNIP3 in the regulation of survival of cancer cells, the influence of oncogenic
      transformation on BNIP3 expression is unclear. MATERIALS AND METHODS: The
      influence of oncogenic transformation on expression of BNIP3 was studied using H
      ras-transformed cells. The consequences of BNIP3 expression for sensitivity to
      CD47-mediated cell death were assessed using tetrazolium salt-based assay.
      RESULTS: Here, the enforced and endogenous expression of Ras coincided with the
      up-regulation of BNIP3 across a wide spectrum of cancer cells, providing the
      first experimental evidence that BNIP3 is a regulatory target of H-Ras. This
      indicated that merely the introduction of a single oncogene may result in the up
      regulation of BNIP3. The consequences of CD47 ligation strongly depended on the
      BNIP3 presence, which in turn correlated with Ras expression. Interestingly, the
      indirect effect of that phenomenon was the selective sensitivity of Ras
      transformed cells to CD47-mediated cell death.

PMID- 21868532
TI  - K-ras mutations in lung tumors from NNK-treated mice with lipopolysaccharide
      elicited lung inflammation.
AB  - BACKGROUND: Chronic lung inflammation has been associated with an increased risk
      of lung cancer. However, it is unclear whether such an event affects the
      incidence of mutations in the K-ras oncogene frequently found in lung tumors and
      suggested to be involved in lung tumorigenesis. This study investigated potential
      impacts of inflammation on the incidence of lung tumors and K-ras mutations using
      a mouse model. MATERIALS AND METHODS: FVB/N mice were treated with
      lipopolysaccharide (LPS) for 16 weeks with or without co-treatment with 4-(methyl
      nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) during the first 4 weeks. RESULTS:
      There was a significant increase in lung inflammatory responses in mice treated
      with LPS and with LPS+NNK, compared with mice treated with NNK or with vehicle.
      The average number of lung tumors per mouse was 3.87 (between 1 and 6) and 0.73
      (between 0 and 3) in mice treated with LPS+NNK and NNK alone, respectively
      (p<0.0001). No lung tumors were observed in mice treated with LPS or vehicle. A
      higher proportion of lung tumors from mice treated with LPS+NNK had K-ras
      mutations, compared with the mice treated with NNK alone (81.03% versus 45.45%,
      p<0.05). CONCLUSION: LPS-elicited chronic lung inflammation significantly
      increases the risk of NNK-mediated lung tumorigenesis in FVB/N mice through K-ras
      gene activation by point mutations.

PMID- 21868533
TI  - Prediction of synergistic antitumour effect of gefitinib and radiation in vitro.
AB  - AIM: This study investigated the potential of a series of biomarkers in
      predicting the interaction of gefitinib and radiation in tumour treatment.
      MATERIALS AND METHODS: In vitro assays were performed on human skin cancer and
      melanoma cell lines. The antitumour effect was measured by using the MTT assay.
      Total and phosphorylated epidermal growth factor receptor (EGFR and pEGFR) levels
      were determined by cell-based ELISA. RESULTS: Gefitinib and radiation interacted
      to inhibit tumour cell proliferation in a cell line-dependent manner. Synergism
      dominated the interaction (76%), followed by additive effect (20%) and a few
      instances of antagonism (4%). Correlation analyses revealed a significant
      correlation between the median combination index (CI) and gefitinib IC50,
      radiation ID50, gefitinib- or EGF-modulated EGFR and/or pEGFR expression (all p
      <= 0.05). CONCLUSION: A potential role of gefitinib efficacy, radiation efficacy
      and gefitinib- or EGF-modulated EGFR and/or pEGFR expression in the prediction of
      interaction between gefitinib and radiation is supported.

PMID- 21868534
TI  - Methylation of the homeobox gene, HOPX, is frequently detected in poorly
      differentiated colorectal cancer.
AB  - BACKGROUND: Homeodomein only protein x (HOPX) gene methylation has frequently
      been detected in cancer tissues. The methylation status of the HOPX gene in
      colorectal cancer was examined and compared to the clinocopathological findings.
      MATERIALS AND METHODS: Eighty-nine tumor samples and corresponding normal tissues
      were obtained from colorectal cancer patients who underwent surgery at our
      hospital. The methylation status of the HOPX gene in these samples was examined
      by quantitative methylation-specific PCR (qMSP). Subsequently, the
      clinicopathological findings were correlated with the methylation status of the
      HOPX gene. RESULTS: HOPX gene methylation was found in 46 (52%) out of the 89
      colorectal carcinomas, suggesting that it was frequently observed in colorectal
      cancer. A significant increase of methylation was observed in the poorly
      differentiated carcinomas (p=0.0049). CONCLUSION: HOPX gene methylation could
      play an important role for the development of colorectal cancer and is closely
      related to the histological type.

PMID- 21868535
TI  - Etodolac improves 5-FU sensitivity of head and neck cancer cells through
      inhibition of thymidylate synthase.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is widely used in the treatment of head and
      neck squamous cell carcinoma (HNSCC). However, development of drug resistance is
      one of the major causes of HNSCC treatment failure. The goal of this study was to
      investigate the mechanism of 5-FU resistance and to develop a novel combination
      therapy with another agent which sensitizes cells to 5-FU. MATERIALS AND METHODS:
      A 5-FU-resistant cell line, UM-SCC-23F/R, was developed from UM-SCC-23 cells. We
      determined sensitivities to 5-FU, etodolac and a combination treatment and also
      analyzed the expressions of cyclooxygenase-2 (COX-2) and thymidylate synthase
      (TS). RESULTS: Selective COX-2 inhibitor, etodolac, sensitized UM-SCC-23F/R cells
      to 5-FU. Expression of COX-2 decreased after etodolac treatment in both cell
      lines. While overexpression of TS was observed in UM-SCC-23F/R cells, etodolac
      inhibited TS expression, suggesting that the sensitizing effect induced by
      etodolac depends on TS suppression. CONCLUSION: We demonstrate for the first time
      an important inhibitory effect of etodolac on TS expression leading to
      sensitization to 5-FU in 5-FU-resistant cells. Our data suggest that TS
      inhibition can be accomplished by this routinely used nonsteroidal anti
      inflammatory drug, and this may have a role as novel effective cancer treatment
      for 5-FU-resistant cancer.

PMID- 21868536
TI  - Down-regulation of expression of interleukin-6 and its receptor results in growth
      inhibition of MCF-7 breast cancer cells.
AB  - Interleukin-6 (IL-6) plays an important role in the neoplastic process through
      its action on cancer cell adhesion, motility, proliferation, tumor-specific
      antigen expression, and thrombopoiesis. IL-6 exerts its activity by binding to a
      high affinity receptor complex consisting of two membrane glycoproteins: the 80
      kDa IL-6 a-receptor subunit (IL-6R) and the 130 kDa signal-transducing protein
      (GP130). In the present study, MCF-7 breast cancer cells were cultured with human
      IL-6 and IL-6 soluble receptor (sIL-6R). MCF-7 cells were also treated with
      either antibodies specific to human IL-6 and IL-6R, or synthetic antisense
      oligodeoxynucleotides (ODNs) targeted to IL-6 and IL-6R genes. Cell growth was
      measured, and it was found that human IL-6 and sIL-6R did not significantly
      increase the proliferation of MCF-7 cells. When IL-6 produced by the MCF-7 cells
      was bound by rabbit anti-human IL-6 antibody, there was a significant dose
      dependent inhibition of cell proliferation. IL-6 and IL-6R antisense ODNs caused
      a marked and specific decrease in IL-6 and IL-6R mRNA and proteins, respectively.
      Both IL-6 and IL-6R antisense ODNs significantly inhibited the proliferation of
      MCF-7 cells, but the inhibitory effect of IL-6R antisense ODN was greater than
      that of IL-6 antisense ODN (IC50: IL-6R: 1 MUM; IL-6: 5 MUM, 72-hour incubation).
      Addition of exogenous IL-6 partially reversed the growth inhibition caused by IL
      6 antisense ODN but not the growth inhibition caused by IL-6R antisense ODN. In
      conclusion, IL-6 plays an important role in maintaining the growth of MCF-7
      breast cancer cells. These results suggest careful modulation of IL-6 and IL-6R
      expression of cells as a potential approach for breast cancer therapy.

PMID- 21868537
TI  - Comparison of MUCT, MRI and optical reflectance imaging for assessing the growth
      of GFP/RFP-expressing tumors.
AB  - AIM: To compare magnetic resonance imaging (MRI), micro-computed tomography
      (MUCT), optical reflectance imaging (ORI) and caliper measurements for
      subcutaneous tumor detection and size assessment. MATERIALS AND METHODS: HCT 116
      green- (GFP)-red-fluorescent protein (RFP) tumor volumes were measured in vivo by
      calipers and by ORI, MRI and MUCT over 15 days and validated ex vivo. The method
      correlating best with the ex vivo tumor volumes was used as reference for
      longitudinal in vivo correlations. RESULTS: MRI and ORI detected tumors at day 1
      post-injection, MUCT after 3 days. The in vivo MRI data correlated best with the
      ex vivo tumor volumes (r2=0.96), followed by MUCT (r2=0.93). Thus, MRI was chosen
      as the reference. MUCT-(r2=0.90), in vivo caliper data (r2=0.80) and fluorescence
      intensities (GFP:r2=0.71; RFP:r2=0.75) highly correlated with MRI-data, whereas
      fluorescent areas (GFP:r2=0.26; RFP:r2=0.30) poorly correlated. CONCLUSION: MRI
      sensitively detects tumors and precisely determines their size; MUCT is an
      accurate alternative for larger tumors; ORI is as sensitive as MRI, but
      overestimates small tumor sizes; and fluorescence intensity correlates better
      with tumor volume than fluorescence area.

PMID- 21868538
TI  - Panipenem does not alter the pharmacokinetics of the active metabolite of
      irinotecan SN-38 and inactive metabolite SN-38 glucuronide (SN-38G) in rats.
AB  - The present study has investigated the effect of panipenem, a widely used
      antibiotic, on the pharmacokinetics of an active metabolite of irinotecan (CPT
      11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G)
      produced by uridine-diphosphate glucuronosyltransferase (UGT) 1A isoform-mediated
      glucuronidation in rats. Rats received a 1 h infusion with panipenem at a loading
      dose of 10 mg/kg and a maintenance dose of 15 mg/min/kg once a day for 5 days.
      When the effect of pretreatment with panipenem on glucuronidation activities of
      substrates for hepatic UGT1A isoforms was investigated using substrates 4
      methylumbelliferone (4MU), estradiol and SN-38, the rate of 4MU glucuronide
      formation was significantly increased, but that of estradiol glucuronide
      formation was unchanged. However, the rate of SN-38G formation showed a tendency
      to increase. One hour after the final infusion of panipenem or saline, SN-38 (2
      mg/kg) was administered intravenously in rats with or without bile duct
      cannulation. Pretreatment with panipenem had no effect on the plasma
      concentration-time curves and biliary excretion of SN-38 and SN-38G in rats with
      and without bile duct cannulation. There were also no significant differences in
      the relative extent of glucuronidation of SN-38 to SN-38G (AUC(2 h, SN-38G)/AUC(2
      h, SN-38)) between panipenem-treated and untreated rats. These findings suggest
      that pretreatment with panipenem does not alter the pharmacokinetics of SN-38 and
      SN-38G, suggesting the possibility that panipenem can be used safely for cancer
      patients undergoing irinotecan chemotherapy.

PMID- 21868539
TI  - CT and MR imaging of the adrenal glands in cortisol-secreting tumors.
AB  - Cushing's syndrome (CS), first described by the neurosurgeon Harvey Cushing in
      the 1930s, is the result of chronic glucocorticoid excess. In patients with
      adreno-corticotropic hormone (ACTH)-dependent CS, bilateral hyperplasia of the
      adrenal cortex occurs, while in those with ACTH-independent primary CS, either
      adrenocortical tumors or primary adrenal hyperplasia can be observed. Cortisol
      secreting adrenocortical tumors are more frequently adenomas, while adrenal
      carcinoma accounts for only 5% of cases. Unfortunately, no reliable
      endocrinological tests are available and no specific tumor markers exist to
      differentiate between benign and malignant adrenal tumors, so both computed
      tomography (CT) and magnetic resonance (MR) imaging studies are currently
      required to localize and define adrenal lesions. Additional information to
      conventional imaging can be obtained using 18F-fluoro-2-deoxyglucose (FDG)
      positron emission tomography (PET)/CT, while percutaneous image-guided fine
      needle aspiration cytology (FNAC) in some cases has shown a high accuracy in
      detecting malignancy and in confirming adrenal metastases. New PET tracers with
      selective affinity for the adrenal tissue are still under evaluation.
      Multidetector CT scan, with the combination of unenhanced and dynamic scans,
      represents the single most accurate modality for the detection and the
      characterization of adrenal adenomas. In these lesions, chemical-shift MR imaging
      produces a typical loss of signal intensity on out-of-phase breath-hold gradient
      echo images in lipid-rich adenomas. For these lesions there is no difference
      between CT and MR imaging, while MR chemical shift imaging is very helpful in
      identifying the additional small group of adenomas where intracellular lipid
      content is minimal.

PMID- 21868540
TI  - Cryotreatment against metastatic renal cell bone tumour reduced multiple lung
      metastases.
AB  - Metastatic renal cell carcinoma (RCC) has a poor response to anticancer
      chemotherapy and radiotherapy. While immunotherapy and molecular targeted drugs
      have been used as first-line therapy for RCC metastasis, the response rate to
      these agents is low. We report the case of a patient with lung and bone
      metastases of RCC whose lung metastases disappeared after reconstruction using
      the resected specimen treated by liquid nitrogen for the bone metastasis. This 60
      year-old female had a left RCC with multiple lung metastases and a left femoral
      bone metastasis at the time of diagnosis. After left nephrectomy followed by
      immunotherapy, we performed tumour excision and reconstruction with frozen
      recycled autograft. The lung metastases had disappeared by 10 months after
      surgery, while serum levels of interferon-gamma and interleukin-12 had increased.
      We postulate that the antitumour activity resulted from immunotherapy plus
      cryotreatment of her bone metastasis and believe that this case supports
      continued research into immunotherapy for cancer.

PMID- 21868541
TI  - Nonhepatic cancer in liver cirrhosis: a retrospective study of prevalence,
      complication rate after specific oncological treatment, follow-up and prognostic
      predictors of outcome in 354 patients with cirrhosis.
AB  - BACKGROUND: Nonhepatic cancer risk of cirrhotic patients seems to be increased.
      Major surgery and chemotherapy in cirrhosis are associated with increased
      mortality and morbidity, which limits treatment. AIM: The aims of this study were
      analysis of (a) prevalence, (b) outcome after treatment, (c) of survival rate and
      (d) predictors of survival in a cirrhotic population. PATIENTS AND METHODS: The
      study population was assembled retrospectively from a database of hospitalized
      patients (n=354). The Kaplan-Meier method was used to calculate the survival
      rate, and Cox regression analysis was performed to identify prognostic
      parameters. RESULTS: Altogether, 84 neoplasms in 70 patients were observed. A
      total of 54 were nonhepatic (15.3%) mainly colorectal carcinoma, prostate cancer
      and tobacco-related neoplasms. TNM stage was the best prognostic parameter
      (p<0.0001). Low bilirubin (p=0.01), normal albumin (p=0.005) and absence of
      ascites (p<0.0001) were also related significantly to longer survival. The rate
      of postinterventional death after specific treatment was high. A proportion of
      patients received no specific therapy due to reduced physical performance, even
      in cases of limited disease. CONCLUSION: Our data confirm the increased risk of
      cirrhotic patients for developing nonhepatic cancer. Advanced TNM stage was
      associated with reduced long-term survival. Scoring systems, such as Child's
      classification and Model of Elevated Liver Disease (MELD) score, were suitable
      parameters to predict mortality. Oncological management in patients with
      cirrhosis must be on an individual basis, independent from TNM classification.

PMID- 21868542
TI  - Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis.
AB  - BACKGROUND: Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been
      associated with a high risk of breast cancer. Since publication of the most
      current meta-analysis of 25(OH)D and breast cancer risk, two new nested case
      control studies have emerged. MATERIALS AND METHODS: A PubMed search for all case
      control studies on risk of breast cancer by 25(OH)D concentration identified 11
      eligible studies. Data from all 11 studies were combined in order to calculate
      the pooled odds ratio of the highest vs. lowest quantile of 25(OH)D across all
      studies. RESULTS: The overall Peto odds ratio summarizing the estimated risk in
      the highest compared to the lowest quantile across all 11 studies was 0.61 (95%
      confidence interval 0.47, 0.80). CONCLUSION: This study supports the hypothesis
      that higher serum 25(OH)D levels reduce the risk of breast cancer. According to
      the review of observational studies, a serum 25(OH)D level of 47 ng/ml was
      associated with a 50% lower risk of breast cancer.

PMID- 21868543
TI  - Basic clinical parameters predict gefitinib efficacy in non-small cell lung
      cancer.
AB  - BACKGROUND: In epidermal growth factor receptor (EGFR)-mutated non-small cell
      lung cancer (NSCLC), the tyrosine-kinase inhibitor gefitinib is in broad use. We
      retrospectively analysed data for 82 patients with advanced NSCLC treated with
      gefitinib and correlated benefits with clinical baseline and therapy-related
      parameters. PATIENTS: Of all patients 48/82 were male; the median age at start of
      gefitinib was 67.2 years; 14/58 informative patients were never-smokers; 57/82
      patients suffered from adenocarcinoma, including 7 with bronchoalveolar
      carcinomas. RESULTS: As to be expected, partial remission was observed in 10% of
      patients, stable disease in 29%, progression-free survival was 3.1 months and
      overall survival 9.2 months. Gefitinib was more efficacious in women, never
      smokers and patients with bronchoalveolar-carcinoma. Furthermore, anemia and
      elevated C-reactive protein levels were unfavourable for therapeutic efficacy.
      Patients developing skin reactions under gefitinib achieved response far more
      frequently, with longer progression-free survival and overall survival.
      CONCLUSION: Basic clinical parameters are good predictors for response to EGFR
      tyrosine-kinase inhibitor therapy, which may be of value if EGFR mutation status
      is not available.

PMID- 21868544
TI  - Palladin is a marker of liver metastasis in primary pancreatic endocrine
      carcinomas.
AB  - BACKGROUND: Palladin is a metastasis-associated gene regulating cell motility.
      The expression of palladin protein in pancreatic neuroendocrine tumors (PET) and
      carcinomas (PECA) is not known. MATERIALS AND METHODS: A tissue microarray (TMA)
      of well-differentiated (WD) PETs/PECAs (AJCC 2010) and non-neoplastic,
      histologically normal pancreatic tissue/islets (HNPIs) was immunostained with
      palladin antibody and quantified using the Allred score. The results were
      correlated with the presence or absence of liver metastases. RESULTS: The
      retrospective study included 19 males and 19 females of age 27-79 years (mean
      54). Tumor size was 0.9-11.5 cm (mean 3.8). Palladin expression was cytoplasmic
      and/or membranous. The tumors with high palladin expression were associated with
      liver metastasis (p<0.0001). All 14 primary PECA with hepatic metastases (MP
      PECAs) exhibited palladin expression whereas 14 out of 24 (58%) clinically
      localized primary PET (CLP-PETs) expressed palladin (p<0.01) with median Allred
      scores of 5 (range 3-7) and 2 (range 0-6) respectively (p<0.0001). The mean
      Allred score for the HNPIs in the MP-PECAs (N=6) was higher (4.2) as compared to
      that in the CLP-PETs (2.5,N=11) (p=0.23). CONCLUSION: Palladin may identify
      primary pancreatic endocrine neoplasms with a propensity to metastasize to the
      liver.

PMID- 21868545
TI  - Elevated YB-1 expression is a new unfavorable prognostic factor in non-Hodgkin's
      lymphomas.
AB  - BACKGROUND: Y-Box-binding protein-1 (YB-1) acts as a transcription factor for
      multiple genes and is linked to DNA replication and repair, cell proliferation
      and resistance to cytostatic drugs. PATIENTS AND METHODS: The prognostic value of
      YB-1 expression in primarily untreated malignant non-Hodgkin's lymphomas (NHLs)
      was examined using immunohistochemistry. RESULTS: Expression of YB-1 was detected
      in 48 out of 56 NHLs, and the immunohistochemical reaction was localized
      exclusively in the cytoplasm. Expression of YB-1 did not correlate with
      clinicopathological variables. Patients with higher YB-1 expression had shorter
      progression-free survival during the entire period of observation (p=0.0434), as
      well as in the course of 30 months' observation (p=0.0253). Additionally, in the
      course of 50 months' observation, patients with higher expression of YB-1
      demonstrated a shorter overall survival time (p=0.0383) and a shorter progression
      free survival (p=0.0309). CONCLUSION: Elevated YB-1 expression may represent a
      new unfavorable prognostic factor.

PMID- 21868546
TI  - The efficacy of gemcitabine as salvage treatment in patients with refractory
      advanced colorectal cancer (CRC): a single institution experience.
AB  - OBJECTIVE: To assess the efficacy of gemcitabine based chemotherapy in heavily
      pre-treated patients with advanced colorectal cancer. PATIENTS AND METHODS:
      Patients, who had been treated with gemcitabine 1250-2000 mg/m2 biweekly in
      combination with capecitabine 1700-2000 mg/m2/day, d1-7 every two weeks were
      retrospectively reviewed. All the patients had previously received at least three
      chemotherapy regimens and 12 (55%) had also received a 4th line regimen. All the
      patients had been treated with a monoclonal antibody either against vascular
      endothelial growth factor receptor (VEGFR) or endothelial growth factor receptor
      (EGFR) (only if wild-type KRAS). The patients had had blood tests weekly,
      carcinoembryonic antigen (CEA) level measurement every 4 weeks and radiological
      assessment of their disease with CT scans every 8/9 weeks. RESULTS: Twenty two
      patients were included; male-female, 14:8; age ranged from 43-73 years. The
      majority of the patients (17/22) had performance status (PS) ECOG 0-1 and the
      remaining patients (5/22) had PS 2 at the time of initiation of the gemcitabine
      based regimen. Thirteen patients demonstrated a clinical benefit (2 partial
      response, 2 minor response, 9 stable disease), 6 patients progressed and 2 were
      not evaluable. CONCLUSION: Gemcitabine has a modest activity in heavily pre
      treated colorectal cancer patients and may be an option in good performance
      status patients.

PMID- 21868547
TI  - RASSF1A methylation is predictive of poor prognosis in female breast cancer in a
      background of overall low methylation frequency.
AB  - Breast cancer (BC) is the most common cancer worldwide. The Kingdom of Saudi
      Arabia is no exception, with ever increasing incidence rates. An interesting
      feature of this disease is the relatively young age of the affected women. The
      average age in the present cohort of 100 sporadic cases of invasive ductal
      carcinomas was 45 years, with a median of 46 years (range between 19-81 years).
      In an effort to understand the molecular signature of BC in the Saudi population,
      we undertook this study to profile the methylation events in a series of key
      genes including Ras association (RalGDS/AF-6) domain family member 1 isoform a
      (RASSF1A), hypermethylated in cancer 1 (HIC1), cyclin-dependent kinase inhibitor
      2A (CDKN2A), retinoic acid receptor beta (RARB2), estrogen receptor 1 (ESR1),
      progesterone receptor (PGR), paired-like homeodomain 2 (PITX2), secreted frizzled
      related protein 1 (SFRP1), myogenic differentiation 1 (MYOD1), and slit homolog 2
      (SLIT2), using MethyLight analysis in archival tumour samples. Interestingly, the
      overall methylation levels were low in this cohort, with only 84% of the cases
      displaying methylation in one or more of the analysed genes. The frequency of
      RASSF1A methylation was the highest (65%), while there was almost complete
      absence of methylation of the ESR1 and the CDH1 genes (1% and 3%, respectively).
      Several statistically significant correlations were identified between specific
      methylation events and clinical parameters which gained more significance when
      analysis was limited to the estrogen receptor positive samples. Although there
      was no significant correlations between any methylation event and disease
      specific survival, methylation of MYOD1 or RASSF1A was associated with lower
      disease-free survival and increased chance of disease recurrence. Furthermore,
      multivariate (Cox) regression analysis identified RASSF1A as an independent
      predictor of poor prognosis in terms of disease-free survival in this cohort. Our
      findings provide further evidence on the usefulness of RASSF1A methylation status
      as an informative prognostic biomarker in BC in a Saudi population.

PMID- 21868548
TI  - Safety and short-term therapeutic effects of miriplatin-lipiodol suspension in
      transarterial chemoembolization (TACE) for hepatocellular carcinoma.
AB  - AIM: To determine the safety and usefulness of a novel anticancer drug,
      miriplatin, in transarterial chemoembolization (TACE) for unresectable
      hepatocellular carcinoma. PATIENTS AND METHODS: Patients (n=115) who underwent
      TACE with miriplatin-lipiodol suspension (miriplatin group), and control patients
      (n=131) who underwent TACE with cisplatin-lipiodol suspension (CDDP group) took
      part in this study. RESULTS: The overall incidence of adverse events was
      significantly lower in the miriplatin group. The percentage of patients attaining
      treatment effect 4 in both groups was not significantly different. The proportion
      exhibiting a >50% decrease in positive tumor markers following TACE was
      significantly greater in the CDDP group for alpha-fetoprotein, but not
      significantly different for des-gammma-carboxy prothrombin. CONCLUSION:
      Miriplatin-lipiodol suspension was associated with reduced intensity of adverse
      events and had comparable short-term therapeutic effects to cisplatin-lipiodol
      suspension, thereby indicating its usefulness in TACE.

PMID- 21868549
TI  - A low-grade myofibroblastic sarcoma in the abdominal cavity.
AB  - Low-grade myofibroblastic sarcoma (LGMFS) is a fusiform cell tumor which develops
      in bone or soft tissues. This type of tumor frequently occurs in the oral cavity
      and extremities, while it is extremely rarely found in the abdominal cavity. This
      article reports a case of LGMFS exceeding 20 cm in diameter in the abdominal
      cavity observed in a 65-year-old male patient. The patient visited our hospital
      complaining of a heavy feeling of the stomach and abdominal distension. Imaging
      examinations revealed a giant solid tumor in the abdomen, and surgical treatment
      was scheduled. During the operation, a tumor about 20 cm in diameter with its
      anterior aspect covered with the greater omentum was found. The tumor had firm
      adhesions to the surrounding tissues, and it was excised with concomitant
      resections of the tail of the pancreas and the spleen. Histopathologically,
      fusiform cells were arranged in a complicated or storiform pattern, and
      immunohistochemical staining revealed that the tumor was positive for alpha
      smooth muscle actin, negative for S100beta, H-caldesmon and c-KIT, and a
      diagnosis of LGMFS was made.

PMID- 21868550
TI  - Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after
      curative resection for non-small cell lung cancer.
AB  - BACKGROUND: The prognostic impact of neutrophil to lymphocyte ratio (NLR) in non
      small cell lung cancer (NSCLC) was examined using patients with a follow-up
      period more than 5 years. PATIENTS AND METHODS: Two hundred and eighty four
      consecutive resected NSCLC patients were reviewed retrospectively. In this study,
      patients who were treated with a follow-up period less than 5 years were omitted,
      RESULTS: The mean value of NLR was 2.44+/-2.22 (range: 0.56-29.44). The 5-year
      survival of the patients with a high NLR (>=2.5) was significantly worse than
      that of the patients with a low NLR (47.06% vs. 67.84%, p<0.0001). Univariate
      analysis of the clinicopathological factors affecting survival revealed that age,
      gender, histology, pT status, pN status, high serum CEA level, positive findings
      of pleural lavage cytology and high NLR were significant risk factors for reduced
      survival. On multivariate analysis, a high NLR was an independent risk factor for
      reduced survival. CONCLUSION: A high preoperative NLR may be a convenient
      biomarker to identify patients with a poor prognosis after resection for NSCLC.

PMID- 21868551
TI  - Lapatinib enhances herceptin-mediated antibody-dependent cellular cytotoxicity by
      up-regulation of cell surface HER2 expression.
AB  - BACKGROUND: Although it was previously reported that lapatinib combined with
      Herceptin improved the progression-free survival rate compared with lapatinib
      alone for patients with Herceptin-refractory HER2-positive metastatic breast
      cancer, the mechanism is purported to be an antiproliferative effect relating to
      the synergism of these two agents. MATERIALS AND METHODS: We evaluated how
      lapatinib interacts with Herceptin in HER2-positive breast cancer, with a
      particular focus on Herceptin-mediated antibody-dependent cellular cytotoxicity
      (ADCC). RESULTS: In an in vitro assay, lapatinib induced HER2 expression at the
      cell surface of HER2-positive breast cancer cell lines, leading to the
      enhancement of Herceptin-mediated ADCC. Furthermore, we present a case report in
      which a second Herceptin treatment following lapatinib resulted in the marked
      shrinkage of multiple metastatic tumors in HER2-positive breast cancer.
      CONCLUSION: Lapatinib may have the potential to convert Herceptin-refractory to
      Herceptin-sensitive tumors in HER2-positive breast cancer by up-regulation of the
      cell surface expression of HER2.

PMID- 21868552
TI  - Paclitaxel and bevacizumab as first line combined treatment in patients with
      metastatic breast cancer: the Hellenic Cooperative Oncology Group experience with
      biological marker evaluation.
AB  - BACKGROUND: Randomized studies have shown that bevacizumab combined with taxane
      based regimens increases response rates and prolongs progression-free survival
      (PFS) of patients with metastatic breast cancer (MBC). However predictive or
      prognostic biological markers that identify the appropriate target population,
      thus improving the cost-effectiveness ratio of this treatment, are still needed.
      PATIENTS AND METHODS: Retrospectively, 124 patients with MBC treated either with
      paclitaxel 90 mg/m2 weekly x12 plus bevacizumab 10 MUg/kg every 2 weeks or 15
      MUg/kg every 3 weeks (85 patients) or paclitaxel 175 mg/m2 plus bevacizumab 15
      MUg/kg every 3 weeks for 6 cycles (36 patients) were identified. Additionally,
      the prognostic significance of a panel of key biological markers was evaluated
      centrally by immunohistochemistry (IHC) in 88 evaluable patients. RESULTS: More
      than two thirds of the patients completed chemotherapy, as planned. The response
      rate was almost identical (55.3% vs. 55.6%) in the patients treated with weekly
      or 3-weekly paclitaxel, respectively. After a median follow-up time of 23 months,
      the median PFS of the study population was 13 months, while median survival had
      not yet been reached. Common severe adverse events were neutropenia (33%),
      neuropathy (18.6%) and metabolic disturbances (17.6%). The incidence of
      hypertension of all grades was 28.1%. High expression of vascular endothelial
      growth factor (VEGF) receptor 3 (VEGFR3) was associated with clinical response,
      while high expression of VEGFR1 was associated with poor survival. CONCLUSION:
      The safety and activity of the combination of bevacizumab with paclitaxel given
      either weekly or 3-weekly in patients with MBC is confirmed.

PMID- 21868553
TI  - Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression
      in gastrointestinal stromal tumors.
AB  - AIM: To characterize the differentially-activated mitogen-activated protein
      kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in
      mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like
      growth factor 1 receptor (IGF1R) expression. MATERIALS AND METHODS: Ninety-nine
      paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117,
      IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E
      binding protein-1 (4EBP1) and pS6 expression were investigated using
      immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived
      growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and
      sequenced. RESULTS: Significant differences were found in the expression of
      phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all
      PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly
      in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R
      expression and either mutational status or pathway activation. CONCLUSION: There
      appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA
      mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs,
      irrespective of mutational status, displayed no IGFR1 expression; tumors positive
      for IGFR1 showed no preferential activation of the MAPK or AKT pathways.

PMID- 21868554
TI  - Correlation of intensity of MT-I/II expression with Ki-67 and MCM-2 proteins in
      invasive ductal breast carcinoma.
AB  - The purpose of the study was to evaluate the clinical significance of the
      intensity of metallothionein (MT-I/II) expression and its relationship to two
      different proliferation markers, Ki-67 antigen and minichromosome maintaince 2
      protein (MCM-2) in 117 patients with invasive ductal breast carcinoma (IDC). A
      significantly higher MT-I/II expression was noted in the grade 3 (G3) carcinomas
      as compared to those of G1 and G2. A positive correlation was observed between
      the MT-I/II expression and both proliferation markers, Ki-67 (r=0.20, p=0.0343)
      and MCM-2 (r=0.25, p=0.0065). Also a strong positive correlation was noted
      between Ki-67 and MCM-2 expression (r=0.52, p<0.0001). No significant
      correlations were found between the analyzed markers and tumour size, lymph node
      metastasis, oestrogen expression (ER), progesterone receptor (PR) or human
      epidermal growth-factor receptor (HER-2) expression. Out of the three studied
      markers only the high expression of Ki-67 exhibited a negative impact on patient
      overall and event free survival and was an independent prognostic factor. MT-I/II
      and MCM-2 protein expression was not correlated with poor patient outcome,
      although MCM-2 expression correlated (Fisher's exact test) positively with grade
      of malignancy (p=0.0018) and negatively with ER (p=0.0002) and PR (p=0.0056)
      expression. To conclude, MT-I/II may play a key role in IDC proliferation, but is
      not a useful prognostic factor of this disease.

PMID- 21868555
TI  - Phase I study of S-1 in combination with trastuzumab for HER2-positive metastatic
      breast cancer.
AB  - BACKGROUND: As there are no reports of S-1 in combination with trastuzumab in
      clinical settings, we evaluated the safety and efficacy of S-1 in combination
      with trastuzumab for human epidermal-growth factor receptor (HER2)-positive
      metastatic breast cancer (MBC) and determined the recommended dose (RD). PATIENTS
      AND METHODS: Patients with HER2-positive MBC received trastuzumab (a fixed
      initial dose of 4 mg/kg/day, then 2 mg/kg every week) plus S-1 (4 weeks followed
      by a 2-week rest) every 42 days. The dosage of S-1 was set of three levels (1: 80
      mg/m2, 2: 65 mg/m2, 3: 50 mg/m2). The purposes of this study were the
      determination of the RD and safety. Dose-limiting toxicity (DLT) data were
      continually monitored to assess S-1 dose decreases. RESULTS: Twelve patients were
      treated at level 1. Because no patients experienced DLT, the RD of S-1 plus
      trastuzumab therapy was 80 mg/m2 S-1 and 4 mg/kg followed by 2 mg/kg trastuzumab.
      The overall response rate and disease control rate were 33.3% and 83.3%,
      respectively. CONCLUSION: S-1 plus trastuzumab could be safely and effectively
      used for the treatment of HER2-positive MBC. The RD for a phase II study of this
      regimen was determined to be 80 mg/m2 S-1 and 2 mg/kg trastuzumab every week
      (loading dose, 4 mg/kg).

PMID- 21868556
TI  - Pathological complete response and prognosis in patients receiving neoadjuvant
      paclitaxel and trastuzumab with and without anthracyclines for stage II and III,
      HER2-positive operable breast cancer: a single-institute experience.
AB  - BACKGROUND: Trastuzumab and various chemotherapy combinations have shown superior
      results in patients with primary and metastatic breast cancer. However,
      cardiotoxicity becomes a major adverse event when trastuzumab is used with
      anthracycline-containing regimens. The purpose of this study was to determine the
      clinical and pathological efficacy of neoadjuvant chemotherapy (NAC), using
      trastuzumab and chemotherapy, with or without anthracyclines, for patients with
      primary breast cancer and human epidermal growth factor receptor 2 (HER2-)
      positive tumors. PATIENTS AND METHODS: A retrospective analysis of 41 patients
      with stage II and III primary breast cancer and HER2-positive tumors treated with
      NAC was performed. NAC consisted of weekly paclitaxel plus trastuzumab with (PTA
      group, n=21) or without anthracycline (PT group, n=20). Patients in the PTA group
      received four courses of 5-fluorouracil, epirubicin, and cyclophosphamide every 3
      weeks followed by concomitant 80 mg/m2 paclitaxel and trastuzumab weekly for 12
      weeks, and those in the PT group received four courses of 80 mg/m2 paclitaxel
      weekly (days 1, 8, and 15) followed by a 1-week break and trastuzumab weekly
      (days 1, 8, 15, and 29). RESULTS: The median age of the patients was 50 years. Of
      41 patients, 21 (51%) had a pathological complete response (pCR). Patients with
      clinical stage II cancer had a higher pCR rate compared with those with clinical
      stage III. Patients with estrogen receptor (ER)-negative tumors showed a trend
      toward a higher pCR rate. No significant difference was observed according age,
      clinical stage, ER status, clinical response, or pathological response between
      the PTA and the PT groups. The pCR rate of the PTA and the PT groups was 47.6%
      and 55.0%, respectively. No significant difference in disease-free survival was
      observed between the two groups at a median follow-up of 32 months. CONCLUSION:
      Trastuzumab-containing NAC is effective irrespective of anthracycline use for
      treating patients with primary breast cancer and HER2-positive tumors.

PMID- 21868557
TI  - Fertility-sparing management of grade 2 and 3 endometrial adenocarcinomas.
AB  - We report four cases of grade 2 and 3 endo-metrial adenocarcinomas managed
      conservatively in order to preserve fertility. In the literature, seven other
      cases have been reported. We discuss the management of these cases and compared
      the carcinologic and fertility outcomes with fertility-sparing management of
      grade 1 endometrial adenocarcinoma.

PMID- 21868558
TI  - Effect of glutathione-S-transferase M1 and T1 allelic polymorphisms on HPV
      induced cervical precancer formation.
AB  - AIM: The effect of GSTM1 and GSTT1 allelic polymorphisms was studied on the HPV
      induced cervical carcinogenesis. PATIENTS AND METHODS: Two hundred and fifty
      three women with persistent high-risk HPV infection were involved in the study;
      117 of them developed cervical high-grade dysplasia and/or cervical
      intraepithelial neoplasia grade III during the 7-year follow-up period.
      Occurrence of GSTM1 and GSTT1 null genotypes was compared between women with and
      without dysplasia. RESULTS: Presence of GSTM1 (OR=1.78, 95% CI=1.06-2.97;
      p=0.028) and GSTT1 (OR=1.89, 95% CI=1.10-3.26; p=0.022) null genotypes was
      statistically significantly more frequent among women with cervical dysplasia
      than in the group without dysplasia. Participants with dual null genotype had an
      even more elevated risk of precancerous lesion (OR=2.35, 95% CI=1.17-4.73;
      p=0.017). CONCLUSION: Our study demonstrated the role of both GSTM1 and T1 null
      genotypes in the development of high-grade cervical dysplasia in a Caucasian
      population.

PMID- 21868559
TI  - Gene polymorphisms MTHFRC677T and MTRA2756G as predictive factors in adjuvant
      chemotherapy for stage III colorectal cancer.
AB  - BACKGROUND: The aim of this study was to explore the effect in stage III
      colorectal cancer of functional gene polymorphisms methylenetetrahydrofolate
      reductase (MTHFR C677T) and methionine synthase (A2756G), in the folate
      metabolism on outcome and risk of toxicity for adjuvant chemotherapy. A secondary
      aim was to investigate any possible interdependency between the two genes.
      PATIENTS AND METHODS: one hundred and fifty randomly chosen patients with stage
      III colorectal cancer, treated with adjuvant chemotherapy, were genotyped by real
      time PCR. Patient and treatment data were retrieved and assessed for demography,
      pathology, chemotherapy tolerability and survival after adjuvant therapy. The
      polymorphisms were studied separately and in combination to discover possible
      interactions. RESULTS: Patients with MTHFR 677 CC genotype carried lower risks of
      suffering from nausea (p=0.027), parasthesia (p=0.0042) and need for dose
      reduction (p=0.025). The CC genotype was also associated with better survival
      (p<0.034). There was interdependency with MTR A2756G. Patients with MTR AG/GG in
      combination with MTHFR CT/TT genotypes carried the highest risk of side-effects.
      CONCLUSION: Functional polymorphisms of MTHFR C677T and MTR A2756G can affect
      outcome and risk of toxicity during adjuvant chemotherapy in stage III colorectal
      cancer. Their possible interdependence brings attention to the function of folate
      metabolism overall regarding its association with 5-fluoruracil related toxicity.
      Our results could explain some of the difficulties of obtaining reproducible and
      uniform results when using single polymorphisms as predictive markers.

PMID- 21868560
TI  - Evaluation of oral etoposide in combination with cisplatin for patients with
      recurrent cervical cancer: long-term follow-up results of a Japanese multicenter
      study.
AB  - AIM: To evaluate the efficacy and toxicities of cisplatin and daily oral
      etoposide in patients with recurrent cervical cancer. PATIENTS AND METHODS:
      Treatment was initiated with oral etoposide 25 mg/day for 21 consecutive days,
      with intravenous cisplatin at 50 mg/m2, on day 1, every 4 weeks, then the
      etoposide dose was increased to 50 mg/day. RESULTS: Thirty patients were enrolled
      in this study. Twenty-seven (90.0%) patients had a history of prior treatment
      (cisplatin with concurrent chemoradiotherapy in 15, radiation therapy in 3,
      chemotherapy in 1, and both radiation therapy and chemotherapy in 9), and 22
      (73.3%) patients had a treatment-free interval of less than 6 months. NCI-CTC
      grade 3/4 hematologic toxicities were leukopenia in 19 (63.3%), neutropenia in 17
      (58.6%), anemia in 15 (50.0%) and thrombocytopenia in 6 (20.0%). Four patients
      developed febrile neutropenia. NCI-CTC grade 3 nonhematologic toxicities
      consisted of nausea/vomiting in 2 (6.7%), anorexia in 4 (13.3%) and fatigue in 2
      (6.7%). The overall response rate was 16.7% including one complete response. The
      median progression-free survival period and overall survival period were 4.5 and
      9.7 months, respectively. CONCLUSION: Combination chemotherapy consisting of oral
      etoposide and intravenous cisplatin is safe and effective for recurrent cervical
      cancer.

PMID- 21868561
TI  - Pleomorphic ductal carcinoma of the male breast: report of a rare case and review
      of literature.
AB  - Male breast carcinoma is a rare neoplasm, accounting for fewer than 1% of all
      malignancies of the breast. We report the case of a 65-year-old man who presented
      at our institution with a lump in his left breast. Histologically, the tumour had
      marked nuclear pleomorphism and contained multinucleated giant cells.
      Immunohistochemical staining demonstrated that the tumour cells were positive for
      cytokeratin AE1/AE3, E-cadherin, p53, Ki-67, cyclin D1, estrogen and progesterone
      receptor proteins, but negative for c-ERB-B2 and CD68. Based on the latest World
      Health Organization classification, the tumour was diagnosed as pleomorphic
      ductal carcinoma of the breast. To the Authors' knowledge, this is the first case
      report of pleomorphic carcinoma of male breast.

PMID- 21868562
TI  - Neoadjuvant chemoradiotherapy for clinical stage II-III esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The clinical significance of neoadjuvant chemoradiotherapy (NACRT)
      for potentially resectable esophageal squamous cell carcinoma (ESCC) is unclear.
      PATIENTS AND METHODS: Patients with clinical stage II-III ESCC were classified
      into an NACRT group (n=76) and surgery alone group (n=92). The prognosis and the
      incidence of postoperative complications were retrospectively investigated. The
      pathological response to NACRT and patient prognosis were also analyzed. RESULTS:
      The 5-year survival rate was 47.7% in the surgery alone group and 56.5% in the
      NACRT group (p=0.4831). The 5-year survival rates of patients in whom NACRT was
      markedly effective was clearly better than that of the other patients
      (ineffective/slightly effective: 36.9%, moderately effective: 53.8%, markedly
      effective: 100%). The incidence of postoperative complications was 31.5% in the
      surgery alone group and 40.8% in the NACRT group (p=0.2121). CONCLUSION: A
      pathological complete response to NACRT is critical for improving the survival of
      patients with clinical stageII-III ESCC.

PMID- 21868563
TI  - Phase I study of neoadjuvant chemoradiotherapy consisting of S-1 and cisplatin
      for patients with resectable advanced gastric cancer (KOGC-01).
AB  - BACKGROUND: The prognosis for advanced gastric cancer is poor, with surgery as
      the only treatment for resectable advanced gastric cancer. Therefore, treatment
      options that might improve the prognosis are needed. To that end, neoadjuvant
      chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated. PATIENTS AND
      METHODS: The chemotherapy schedule included one cycle repeated after 6 weeks. S-1
      was administered orally every day on days 1-21 and CDDP was infused on days 1, 8
      and 15. Radiation therapy was started concurrently with chemotherapy and repeated
      daily on days 1-5, 8-12, 15-19, and 22-26. RESULTS: A total of 10 patients were
      recruited. The first four patients were entered into level 1 (CDDP, 20 mg/m2).
      The next six patients were entered into level 0 (15 mg/m2), because of dose
      limiting toxicity (delaying the second course of chemotherapy in two patients)
      that had been observed at level 1. The maximum tolerated dose (MTD) of CDDP was
      20 mg/m2. Seven patients underwent surgery and all had an R0 (no residual tumor)
      resection without surgical complications. CONCLUSION: Neoadjuvant
      chemoradiotherapy with S-1 and CDDP may cause surgery to be delayed, but shows
      promise for resectable advanced gastric cancer.

PMID- 21868564
TI  - Feasibility study of triplet combination chemotherapy of paclitaxel, cisplatin
      and S-1 for advanced gastric cancer.
AB  - BACKGROUND: Docetaxel combined with cisplatin and 5-fluorouracil (5-FU) is active
      in advanced gastric cancer, but not generally accepted because of its substantial
      toxicities. We conducted a feasibility study of a triplet combination using
      paclitaxel, cisplatin and S-1 for advanced gastric cancer. PATIENTS AND METHODS:
      Patients were given paclitaxel 160 mg/m2 infused over 2 hours on day 1, followed
      by cisplatin 60 mg/m2 in a 2-hour infusion on day 14, and S-1 80 mg/m2/day for 14
      consecutive days, followed by a 2-week rest, repeated every 4 weeks. Treatment
      was continued until disease progression or unacceptable toxicity occurred, the
      patient refused the therapy, or a surgical procedure was performed. RESULTS:
      Twenty-one patients were prospectively enrolled. A total of 53 courses were
      administered, with a median of 2 courses (range: 1-7). Leucopenia, neutropenia,
      and anemia of grade 3 or more occurred in 3, 12, and 3 patients, respectively.
      Non-hematological toxicities were all grade 2 or less. Planned treatment was
      delivered with relative dose intensity for paclitaxel, cisplatin, and S-1 as
      91.1%, 81.1% and 90.6%, respectively. The overall response rate was 67% with 1
      complete response, 13 partial responses, and 6 with stable disease, while 6 out
      of 13 surgically resected specimens showed a histologic response graded >= 1b.
      Median survivals of all patients and of 13 patients who underwent curative
      resection were 543 and 871 days, respectively. CONCLUSION: Triplet combination
      chemotherapy with paclitaxel, cisplatin and S-1 demonstrated superior feasibility
      and promising antitumor activity for advanced gastric cancer.

PMID- 21868565
TI  - Evaluation of kallikrein-related peptidase 5 expression and its significance for
      breast cancer patients: association with kallikrein-related peptidase 7
      expression.
AB  - BACKGROUND: Kallikrein-related peptidases (KLKs) have been proposed as potential
      cancer biomarkers. Contradictions in literature led us to clarify the role of
      KLK5 as a breast cancer predictor, as well as its association with KLK7
      expression. PATIENTS AND METHODS: Semi-quantitative RT-PCR detected KLKs 5 and 7
      in 80 breast tissues, 74 neoplastic and 6 normal. Steroid hormone receptors were
      quantified in all samples. Associations between KLK5 status and
      clinicopathological variables, as well as disease-free survival (DFS) and overall
      survival (OS) of patients were analyzed. RESULTS: Forty tumor tissues showed high
      KLK5 expression, which was significantly associated with estrogen receptor
      status. Significant co-expression of KLKs 5 and 7 was observed in the same cancer
      samples (p=0.02). Increased KLK5 expression was a statistically significant
      independent prognostic factor for DFS (p=0.009 univariate analysis and p=0.028
      multivariate analysis) and OS of patients (p=0.014, univariate analysis).
      CONCLUSION: Increased KLK5 expression can contribute to the prognosis of DFS and
      OS of breast cancer patients. KLKs 5 and 7 are co-expressed in breast cancer.

PMID- 21868566
TI  - Sifneos alexithymia questionnaire in assessment of general alexithymia in
      patients with breast disease and breast cancer: a prospective case-control study
      in Finland.
AB  - BACKGROUND: In 1973, Sifneos introduced the word 'alexithymia' to describe the
      inability to find appropriate words to describe one's feelings. To the Authors'
      knowledge, the associations between alexithymia and the risk of breast cancer
      (BC) are rarely considered together in a prospective study. PATIENTS AND METHODS:
      In an extension of the Kuopio Breast Cancer Study 115 women with breast symptoms
      were semi-structurally interviewed in-depth, as well as being asked to complete
      standardised questionnaires (Beck, Forsen, MADRS, Spielberger), and all study
      variables were obtained before any diagnostic procedures were carried out. The
      investigator estimated the alexithymia of the study participants using a 5-point
      scale. RESULTS: The clinical examination and biopsy showed BC in 34 patients,
      benign breast disease (BBD) in 53 patients, and 28 individuals were shown to be
      healthy (HSS). There was a significance for the women with BC to have more
      alienation from own body (Function C, p=0.03) (mean Alexithymia score, 2.82) than
      those of the BBD (mean Alexithymia score, 3.40) and HSS groups (mean Alexithymia
      score, 3.29). The BC group had significantly more alienation from own experience
      (Function D, p=0.01) (mean Alexithymia score, 2.82) than the patients in the BBD
      group (mean Alexithymia score, 3.51) and in the HSS group (mean Alexithymia
      score, 3.36). The BC group also had more alienation from own feelings (Function
      E, p=0.05) and more deficit in self-experience (Function F, p=0.05) than the
      patients in the BBD group and the patients in the HSS group. CONCLUSION: The
      results of this study show that the patients with BC tended to have an increased
      risk for alexithymia.

PMID- 21868567
TI  - The role of MonoTotal in the primary diagnosis, prognosis and follow-up of
      patients with non-small cell lung cancer (NSCLC).
AB  - BACKGROUND: A new cytokeratin tumor marker, MonoTotal was studied in lung cancer,
      the most common cause of cancer mortality worldwide. In non-small cell lung
      cancer (NSCLC) patients MonoTotal serum levels and their relationship to the
      tumor stage, histological subtype, early relapse and cancer-related death were
      evaluated. PATIENTS AND METHODS: MonoTotal serum levels were studied, using
      immunoradiometric assay in a group of 93 patients with newly diagnosed NSCLC
      undergoing radical surgery, and were compared to those with benign lung diseases.
      RESULTS: A diagnostic power of MonoTotal in distinguishing patients with NSCLC
      from benign lung diseases was demonstrated. Higher levels of MonoTotal were
      associated with advanced stages of squamous cell carcinoma and there was a
      positive correlation of marker with tumor size. Marker levels showed significant
      relation to disease-free survival and overall survival. CONCLUSION: MonoTotal
      seems to be a potentially very interesting serum marker that, in conjunction with
      other clinical data, might be used for monitoring of patients with NSCLC.

PMID- 21868569
TI  - JAM-B regulates maintenance of hematopoietic stem cells in the bone marrow.
AB  - In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow (BM)
      and are maintained in a quiescent and undifferentiated state through adhesive
      interactions with specialized microenvironmental niches. Although junctional
      adhesion molecule-C (JAM-C) is expressed by HSCs, its function in adult
      hematopoiesis remains elusive. Here, we show that HSCs adhere to JAM-B expressed
      by BM stromal cells in a JAM-C dependent manner. The interaction regulates the
      interplay between HSCs and BM stromal cells as illustrated by the decreased pool
      of quiescent HSCs observed in jam-b deficient mice. We further show that this is
      probably because of alterations of BM stromal compartments and changes in SDF
      1alpha BM content in jam-b(-/-) mice, suggesting that JAM-B is an active player
      in the maintenance of the BM stromal microenvironment.

PMID- 21868570
TI  - Implications of discrepancy in morphologic diagnosis of myelodysplastic syndrome
      between referral and tertiary care centers.
AB  - Patients referred to tertiary care centers occasionally may have their diagnostic
      procedures repeated and have a final diagnosis that differs from that of the
      referring center. The aim of this study was to evaluate discordance rates and
      their clinical implications in the diagnosis of patients with myelodysplastic
      syndrome (MDS) referred to a tertiary center. We analyzed 915 patients with MDS
      who were referred to M. D. Anderson Cancer Center between September 2005 and
      December 2009. Discordance in the diagnosis was documented in 109 (12%) patients,
      with a majority reclassified as having higher-risk disease by French-American
      British (67%) or by International Prognostic Scoring System (77%) with
      implications for therapy selection and prognosis calculation. These results
      demonstrate the complexity of the diagnosis of MDS and highlight the need for
      confirmation of diagnosis when in doubt.

PMID- 21868572
TI  - A 2-step approach to myeloablative haploidentical stem cell transplantation: a
      phase 1/2 trial performed with optimized T-cell dosing.
AB  - Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have
      identified threshold doses of T cells below which severe GVHD is usually absent.
      However, little is known regarding optimal T-cell dosing as it relates to
      engraftment, immune reconstitution, and relapse. To begin to address this
      question, we developed a 2-step myeloablative approach to haploidentical HSCT in
      which 27 patients conditioned with total body irradiation (TBI) were given a
      fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for
      T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after
      CY. A dose of 2 * 10(8)/kg of T cells resulted in consistent engraftment, immune
      reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III
      IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%,
      22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year
      probability of overall survival for the whole cohort is 48% and 75% in patients
      without disease at HSCT. In the context of CY tolerization, a high, fixed dose of
      haploidentical T cells was associated with encouraging outcomes, especially in
      good-risk patients, and can serve as the basis for further exploration and
      optimization of this 2-step approach. This study is registered at
      www.clinicaltrials.gov as NCT00429143.

PMID- 21868571
TI  - p53 activation of mesenchymal stromal cells partially abrogates microenvironment
      mediated resistance to FLT3 inhibition in AML through HIF-1alpha-mediated down
      regulation of CXCL12.
AB  - Fms-like tyrosine kinase-3 (FLT3) inhibitors have been used to overcome the
      dismal prognosis of acute myeloid leukemia (AML) with FLT3 mutations. Clinical
      results with FLT3 inhibitor monotherapy have shown that bone marrow responses are
      commonly less pronounced than peripheral blood responses. We investigated the
      role of p53 in bone marrow stromal cells in stromal cell-mediated resistance to
      FLT3 inhibition in FLT3 mutant AML. While the FLT3 inhibitor FI-700 induced
      apoptosis in FLT3 mutant AML cells, apoptosis induction was diminished under
      stromal coculture conditions. Protection appeared to be mediated, in part, by
      CXCL12 (SDF-1)/CXCR4 signaling. The protective effect of stromal cells was
      significantly reduced by pre-exposure to the HDM2 inhibitor Nutlin-3a. p53
      activation by Nutlin-3a was not cytotoxic to stromal cells, but reduced CXCL12
      mRNA levels and secretion of CXCL12 partially through p53-mediated HIF-1alpha
      down-regulation. Results show that p53 activation in stroma cells blunts stroma
      cell-mediated resistance to FLT3 inhibition, in part through down-regulation of
      CXCL12. This is the first report of Nutlin effect on the bone marrow environment.
      We suggest that combinations of HDM2 antagonists and FLT3 inhibitors may be
      effective in clinical trials targeting mutant FLT3 leukemias.

PMID- 21868573
TI  - Regulation of memory B-cell survival by the BH3-only protein Puma.
AB  - Apoptosis is crucial for immune system homeostasis, including selection and
      survival of long-lived antibody-forming cells and memory cells. The interactions
      between proapoptotic and pro-survival proteins of the Bcl-2 family are critical
      for this process. In this report, we show that expression of the proapoptotic BH3
      only Bcl-2 family member Puma was selectively up-regulated on in vitro activation
      with antigens or mitogens of both human and mouse B cells. Puma expression
      coincided in vivo, with the prosurvival Bcl-2 family member Mcl-1 within the
      germinal centers and its expression correlates with the germinal center like
      phenotype of Burkitt lymphoma. Experiments performed in Puma-deficient mice
      revealed that Puma is essential for apoptosis of mitogen-activated B cells in
      vitro and for the control of memory B-cell survival. In conclusion, using both
      human and murine models, our data show that Puma has a major role in the T cell-
      dependent B-cell immune response. These data demonstrate that Puma is a major
      regulator of memory B lymphocyte survival and therefore a key molecule in the
      control of the immune response.

PMID- 21868574
TI  - Novel protein ADTRP regulates TFPI expression and function in human endothelial
      cells in normal conditions and in response to androgen.
AB  - Thrombosis and cardiovascular disease (CVD) represent major causes of morbidity
      and mortality. Low androgen correlates with higher incidence of CVD/thrombosis.
      Tissue Factor Pathway Inhibitor (TFPI) is the major inhibitor of tissue factor
      factor VIIa (TF-FVIIa)-dependent FXa generation. Because endothelial cell (EC)
      dysfunction leading to vascular disease correlates with low EC-associated TFPI,
      we sought to identify mechanisms that regulate the natural expression of TFPI.
      Data mining of NCBI's GEO microarrays revealed strong coexpression between TFPI
      and the uncharacterized protein encoded by C6ORF105, which is predicted to be
      multispan, palmitoylated and androgen-responsive. We demonstrate that this
      protein regulates both the native and androgen-enhanced TFPI expression and
      activity in cultured ECs, and we named it androgen-dependent TFPI-regulating
      protein (ADTRP). We confirm ADTRP expression and colocalization with TFPI and
      caveolin-1 in ECs. ADTRP-shRNA reduces, while over-expression of ADTRP enhances,
      TFPI mRNA and activity and the colocalization of TF-FVIIa-FXa-TFPI with caveolin
      1. Imaging and Triton X-114-extraction confirm TFPI and ADTRP association with
      lipid rafts/caveolae. Dihydrotestosterone up-regulates TFPI and ADTRP expression,
      and increases FXa inhibition by TFPI in an ADTRP- and caveolin-1-dependent
      manner. We conclude that the ADTRP-dependent up-regulation of TFPI expression and
      activity by androgen represents a novel mechanism of increasing the anticoagulant
      protection of the endothelium.

PMID- 21868576
TI  - Is heparin a placental anticoagulant in high-risk pregnancies?
AB  - Randomized control trials show beneficial effects of heparin in high-risk
      pregnancies to prevent preeclampsia and intrauterine growth restriction. However,
      the lack of placental pathology data in these trials challenges the assumption
      that heparin is a placental anticoagulant. Recent data show that placental
      infarction is probably associated with abnormalities in development of the
      placenta, characterized by poor maternal perfusion and an abnormal villous
      trophoblast compartment in contact with maternal blood, than with maternal
      thrombophilia. At-risk pregnancies may therefore be predicted by noninvasive
      prenatal testing of placental function in mid-pregnancy. Heparin has diverse
      cellular functions that include direct actions on the trophoblast. Dissecting the
      non-anticoagulant actions of heparin may indicate novel and safer therapeutic
      targets to prevent the major placental complications of pregnancy.

PMID- 21868575
TI  - A novel inhibitor of focal adhesion signaling induces caspase-independent cell
      death in diffuse large B-cell lymphoma.
AB  - Focal adhesion (FA) proteins have been associated with transformation, migration,
      metastasis, and poor outcome in many neoplasias. We previously showed that these
      proteins were inhibited by E7123, a new celecoxib derivative with antitumor
      activity, in acute myeloid leukemia. However, little is known about FAs in
      diffuse large B cell lymphoma (DLBCL). This paper aimed to determine whether
      E7123 was effective against DLBCL and whether FAs were involved in its action. We
      evaluated the cytotoxicity and mechanism of action of E7123 and celecoxib in
      DLBCL cell lines. We also assessed the E7123 in vivo activity in a DLBCL
      xenograft model and studied FA signaling in primary DLBCL patient samples. We
      found that E7123 showed higher antitumor effect than celecoxib against DLBCL
      cells. Its mechanism of action involved deregulation of FA, AKT, and Mcl-1
      proteins, a pathway that is activated in some patient samples, apoptosis-inducing
      factor release and induction of caspase-independent cell death. Moreover, E7123
      showed suppression of in vivo tumor growth. These findings indicate that E7123 is
      effective against DLBCL in vitro and in vivo, with a mechanism of action that
      differs from that of most current therapies for this malignancy. Our results
      support further preclinical evaluation of E7123.

PMID- 21868577
TI  - Funding mechanisms and program management at the National Heart, Lung, and Blood
      Institute: confronting new challenges and exploring new opportunities.
AB  - Over the past 8 years, the National Institutes of Health (NIH) budget
      appropriation has lost purchasing power, with erosion of the benefits of the
      doubling of the budget less than a decade ago. For the first time in 40 years,
      the NIH appropriation in fiscal year 2011 was 1% less than in the previous year.
      The National Heart, Lung, and Blood Institute (NHLBI) has been closely managing
      its funds to protect its core functions: support and conduct of research, and
      training of biomedical research scientists. Rigorous evaluations of funding
      mechanisms, management of clinical studies, set-aside programs and funding
      guidelines are designed to help the Institute, in consultation with its advisory
      council, to minimize the long-term impact of extreme resource limitations on the
      advance and conduct of science. This report describes some recent actions taken
      by the NHLBI to maximize support for investigator-initiated research, maintain a
      balanced portfolio, and provide as much support as possible for established and
      early-stage investigators.

PMID- 21868578
TI  - Donor immunization with WT1 peptide augments antileukemic activity after MHC
      matched bone marrow transplantation.
AB  - The curative potential of MHC-matched allogeneic bone marrow transplantation
      (BMT) is in part because of immunologic graft-versus-tumor (GvT) reactions
      mediated by donor T cells that recognize host minor histocompatibility antigens.
      Immunization with leukemia-associated antigens, such as Wilms Tumor 1 (WT1)
      peptides, induces a T-cell population that is tumor antigen specific. We
      determined whether allogeneic BMT combined with immunotherapy using WT1 peptide
      vaccination of donors induced more potent antitumor activity than either therapy
      alone. WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that
      were specifically reactive to WT1-expressing FBL3 leukemia cells. We found that
      peptide immunization was effective as a prophylactic vaccination before tumor
      challenge, yet was ineffective as a therapeutic vaccination in tumor-bearing
      mice. BMT from vaccinated healthy MHC-matched donors, but not syngeneic donors,
      into recipient tumor-bearing mice was effective as a therapeutic maneuver and
      resulted in eradication of FBL3 leukemia. The transfer of total CD8(+) T cells
      from immunized donors was more effective than the transfer of WT1
      tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal
      antitumor activity. These findings show that WT1 peptide vaccination of donor
      mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.

PMID- 21868579
TI  - Angiopoietin-2 promotes myeloid cell infiltration in a beta2-integrin-dependent
      manner.
AB  - In human inflammatory diseases, we identified endothelial angiopoietin-2 (Ang-2)
      expression to be strongly associated with inflammations mediated by myeloid cells
      but not lymphocytes. To identify the underlying mechanism, we made use of a
      transgenic mouse model with inducible endothelial cell-specific expression of Ang
      2. In this model, in the absence of inflammatory stimuli, long-term expression of
      Ang-2 led to a time-dependent accumulation of myeloid cells in numerous organs,
      suggesting that Ang-2 is sufficient to recruit myeloid cells. In models of acute
      inflammation, such as delayed-type hypersensitivity and peritonitis, Ang-2
      transgenic animals showed an increased responsiveness. Intravital fluorescence
      video microscopy revealed augmented cell adhesion as an underlying event.
      Consequently, we demonstrated that Ang-2 is able to induce strong monocyte
      adhesion under shear in vitro, which could be blocked by antibodies to beta2
      integrin. Taken together, our results describe Ang-2 as a novel, endothelial
      derived regulator of myeloid cell infiltration that modulates beta2-integrin
      mediated adhesion in a paracrine manner.

PMID- 21868580
TI  - Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype,
      storage cell markers, and therapeutic response.
AB  - Gaucher disease, caused by a deficiency of the lysosomal enzyme
      glucocerebrosidase, leads to prominent glucosylceramide accumulation in lysosomes
      of tissue macrophages (Gaucher cells). Here we show glucosylsphingosine, the
      deacylated form of glucosylceramide, to be markedly increased in plasma of
      symptomatic nonneuronopathic (type 1) Gaucher patients (n = 64, median = 230.7
      nM, range 15.6-1035.2 nM; normal (n = 28): median 1.3 nM, range 0.8-2.7 nM). The
      method developed for mass spectrometric quantification of plasma
      glucosylsphingosine is sensitive and robust. Plasma glucosylsphingosine levels
      correlate with established plasma markers of Gaucher cells, chitotriosidase (rho
      = 0.66) and CCL18 (rho = 0.40). Treatment of Gaucher disease patients by
      supplementing macrophages with mannose-receptor targeted recombinant
      glucocerebrosidase results in glucosylsphingosine reduction, similar to protein
      markers of Gaucher cells. Since macrophages prominently accumulate the
      lysoglycosphingolipid on glucocerebrosidase inactivation, Gaucher cells seem a
      major source of the elevated plasma glucosylsphingosine. Our findings show that
      plasma glucosylsphingosine can qualify as a biomarker for type 1 Gaucher disease,
      but that further investigations are warranted regarding its relationship with
      clinical manifestations of Gaucher disease.

PMID- 21868582
TI  - New aspects of Filamin A versatility.

PMID- 21868583
TI  - The risks of informed decision-making.

PMID- 21868584
TI  - DBA, del(5q): a reciprocal relationship.

PMID- 21868585
TI  - GVHD-free with Campath?

PMID- 21868587
TI  - Pilot physical activity intervention reduces severity of ADHD symptoms in young
      children.
AB  - OBJECTIVE: Physical activity associates with mental health and neurocognitive
      function, showing potential for addressing ADHD symptoms. As a preliminary
      assessment of this potential, the authors piloted a before-school physical
      activity intervention for young children. METHOD: Seventeen children (Grades K-3)
      exhibiting four or more hyperactivity/impulsivity symptoms on the Disruptive
      Behavior Disorders Rating Scale (Pelham, 2002) completed about 26 min of
      continuous moderate-to-vigorous physical activity daily over eight school weeks.
      The authors administered cognitive, motor, social, and behavioral functioning
      measures at pre- and postprogram, assessed response inhibition weekly, and coded
      negative behaviors daily. RESULTS: Several measures showed significant or
      marginally significant change over time (effect size = 0.35-0.96) with additional
      measures showing meaningful effect size values (>= 0.20). Response inhibition
      effects were most consistent. Most participants (64% to 71%) exhibited overall
      improvement according to postprogram parent, teacher, and program staff ratings.
      CONCLUSION: Physical activity shows promise for addressing ADHD symptoms in young
      children.

PMID- 21868588
TI  - Effects of symptoms of ADHD, ODD, and cognitive functioning on social acceptance
      and the positive illusory bias in children.
AB  - OBJECTIVE: To examine the effects of symptoms of ADHD and ODD and cognitive
      functioning on social acceptance and positive bias in children. METHOD: The
      sample consisted of 86 children (49 girls) between 7 and 13 years old, recruited
      to reflect a wide range of ADHD symptoms. Parents and teachers reported on ADHD
      and ODD symptoms and social acceptance. Children reported on social acceptance
      and were given tasks measuring working memory, inhibition and reaction-time
      variability. A discrepancy score between child and adult reports of social
      acceptance was used as a measure of positive bias. RESULTS: Inattention
      independently explained variance in social acceptance. The cognitive factors were
      related to social acceptance and the positive bias, but not beyond the ADHD and
      ODD symptoms. CONCLUSION: It is primarily disruptive behavior that contributes to
      external reports of children's social acceptance.

PMID- 21868589
TI  - Carbendazim combined with imazalil or cypermethrin potentiate DNA damage in
      hepatocytes of mice.
AB  - Traces of pesticides imazalil, cypermethrin and carbendazim are detected in
      plants used for human consumption. To explore whether their application in oral
      combinations will induce DNA breaks in hepatocytes, a subchronic in vivo
      experiment was performed in Swiss mice. Doses of 10 mg kg(-1) of imazalil (im)
      and cypermethrin (cy), and 20 mg kg(-1) of carbendazim (car) and their
      combinations (im, 10 mg kg(-1) + cy, 10 mg kg(-1); im, 10 mg kg(-1) + car, 20 mg
      kg(-1); car, 20 mg kg(-1) + cy, 10 mg kg(-1)) were applied daily for 28 days.
      Afterward, DNA damage in hepatocytes was evaluated by comet assay. Individually,
      imazalil and cypermethrin damaged DNA at alkali-labile sites, while the tail
      moment (TM) of carbendazim alone was similar to control but with higher tail
      length. In combination with carbendazim clastogen, properties of imazalils and
      cypermethrins were potentiated compared to all other treatments and control.
      There were pronounced sex differences in pattern of fragmentation between treated
      groups. Higher long tail nuclei (LTN) in females indicate that certain cells in
      females were especially prone to total nucleus disintegration. Due to synergistic
      effects, low environmentally present concentrations of imazalil and cypermethrin
      in food, and especially their mixtures with carbendazim have genotoxic potential
      that could be particularly dangerous over prolonged exposure in mammalian
      organism.

PMID- 21868590
TI  - Piloting group well child visits in pediatric resident continuity clinic.
AB  - INTRODUCTION: Well child care is taught with individual visits in pediatric
      residency. Teaching residents how to deliver well child care efficiently is
      critical. Group well child care brings multiple families together for visits. The
      authors piloted group visits in pediatric residency clinic. METHODS: The authors
      conducted group visits for 1- to 12-month old children. Seven families completed
      the group visits and were surveyed. Nine residents (intervention group) conducted
      group visits. Eighteen months after implementation, the intervention and control
      groups in the same clinic surveyed. RESULTS: All families recommended group
      visits. The intervention group residents reported significantly more direct
      observations (P < .05). Trends toward improvement of teaching and role modeling
      for the intervention group were also observed. DISCUSSION: The authors'
      continuity clinic had success implementing group visits, and families were
      recommended the visits. Group visits offer a natural environment to observe
      residents while exposing them to another way to deliver well child care.

PMID- 21868591
TI  - Evaluation of the precision of emergency department diagnoses in young children
      with fever.
AB  - OBJECTIVE. To characterize causes of fever in children presenting to a pediatric
      emergency department (ED). METHODS. One-year retrospective review of ED records.
      Inclusion criteria were 2 to 36 months of age with a documented temperature >= 39
      degrees C. Exclusion criteria were elopement, repeat visit, and underlying
      diagnosis with a predisposition to infection. Medical records were reviewed using
      a predefined, study-specific, data abstraction tool. Based on diagnosis and
      pathogen detection, visits were assigned to 3 groups, laboratory confirmed
      pathogen and focal or nonfocal diagnosis without confirmed pathogen. RESULTS. A
      total of 1091 visits met inclusion criteria. Fourteen percent had a pathogen
      detected, 56% had a focal diagnosis without a confirmed pathogen, and 30% had a
      nonfocal diagnosis without confirmed pathogen. CONCLUSIONS. In a cohort of
      febrile children 2 to 36 months of age, only 14% had a confirmed pathogen. New
      rapid viral diagnostic techniques may provide an opportunity to improve
      diagnostic certainty in young children presenting with fever.

PMID- 21868593
TI  - Fever and stiff neck.

PMID- 21868592
TI  - Detours on the road to diagnosis of Graves disease.
AB  - OBJECTIVES: The aims of this study were to determine the frequency at which
      spurious diagnoses and unnecessary treatment occurs prior to the diagnosis of
      Graves disease (GD) and to evaluate the economic consequences of these events.
      METHODS: Retrospective chart review of children diagnosed with GD. RESULTS: A
      total of 76 children (61 girls) aged 11.9 +/- 3.8 years were identified. In all,
      17 (22.4%) were referred to other subspecialists prior to diagnosis of GD. Six
      were hospitalized, and 2 visited emergency rooms. A total of 15 (19.7%) underwent
      nonthyroid-related studies. Estimated cost of testing and procedures ranged from
      $49 to $14,000. Twelve (15.8%) were diagnosed with attention
      deficit/hyperactivity disorder, and 16 (21.1%) were started on medications for
      other conditions prior to diagnosis of GD. CONCLUSIONS: Evaluation and treatment
      for presumed other disorders are common in children with GD. A high index of
      suspicion for hyperthyroidism by primary care providers may help to avoid
      clinical detours that may be costly and delay diagnosis.

PMID- 21868594
TI  - Family functioning and coping styles in families of children with cancer and HIV
      disease.
AB  - Disease-specific characteristics of pediatric illnesses may influence the
      functioning of families and the coping responses they enact. This study compared
      family functioning and coping styles within and between 2 different medical
      groups: families of children with cancer (n = 44) and HIV disease (n = 65). Most
      caregivers reported healthy family functioning, and no between-group differences
      in functioning emerged. However, with regard to coping, more reliance on social
      support was indicated among the cancer group. Also, the HIV group largely sought
      support from family, whereas both family and nonfamily support were sought among
      the cancer group. Better functioning was related to reframing, an active coping
      style, within the cancer group and passive coping within the HIV group. Thus,
      coping strategies and their implications for family functioning vary by
      condition. Researchers should avoid combining various illness groups
      indiscriminately. Likewise, clinicians should be sensitive to disease-specific
      factors when helping families learn to cope with illness-related stressors.

PMID- 21868595
TI  - Economic and radiation costs of initial imaging approaches after a child's first
      febrile urinary tract infection.
AB  - BACKGROUND. The traditional initial imaging approach following pediatric urinary
      tract infection is the "bottom-up" approach (cystogram and renal ultrasound).
      Recently, the "top-down" approach (nuclear renal scan followed by cystogram for
      abnormal scans only) has gained increasing attention. The relative cost and
      radiation doses of these are unknown METHODS. The authors used a decision model
      to evaluate these imaging approaches. Cost and effective radiation dose
      estimates, including sensitivity analyses, were based on one-time imaging only.
      RESULTS. Comparing hypothetical cohorts of 100 000 children, the top-down imaging
      approach cost $82.9 million versus $59.2 million for the bottom-up approach. Per
      capita effective radiation dose was 0.72 mSv for top-down compared with 0.06 mSv
      for bottom-up. CONCLUSIONS. Routine use of nuclear renal scans in children
      following initial urinary tract infection diagnosis would result in increased
      imaging costs and radiation doses as compared to initial cystogram and
      ultrasound. Further data are required to clarify the long-term clinical
      implications of this increase.

PMID- 21868596
TI  - Parent medication concerns predict underutilization of mental health services for
      minority children with ADHD.
AB  - OBJECTIVE. Disparities in attention deficit hyperactivity disorder (ADHD)
      treatment are recognized with minority children using services less than
      nonminority children. The authors examine minority parents' knowledge and
      perceptions of ADHD as they relate to service utilization. METHODS. Using a
      longitudinal cohort design, parents of children with untreated ADHD were surveyed
      regarding their knowledge and perceptions of ADHD and then followed for 3 to 6
      months to determine whether they used services. RESULTS. Seventy parents of 5- to
      18-year-old children with untreated ADHD were enrolled. Of the 70 children, 33
      (47.1%) had not attended any mental health appointments and 51 (72.9%) had not
      used any treatments by 3- to 6-month follow-up. Logistic regression indicated
      that increasing age and medication concerns were associated with less follow-up
      at mental health appointments (P < .05) and less utilization of treatments (P <
      .05). CONCLUSIONS. The results of this study highlight the importance of
      addressing medication concerns, when referring minority children to mental health
      services or offering treatments.

PMID- 21868597
TI  - Pediatric autonomic testing: retrospective review of a large series.
AB  - OBJECTIVE. To describe the reasons for referral, autonomic diagnoses, test
      results, and patient management in a large pediatric population referred for
      testing for an autonomic disorder. DESIGN. The authors reviewed autonomic testing
      data and medical records for patients aged 18 years and younger who underwent
      testing between 1993 and 2007 and who had adequate clinical data. Relevance of
      test results to clinical symptoms was ranked on a 3-point scale. Treatments were
      noted and their benefit ranked on a 5-point scale. RESULTS. Among 142 pediatric
      patients identified, postural tachycardia syndrome was most common (71%) while
      orthostatic hypotension was rare (5%). Testing provided relevant information
      regarding the patient's symptoms in 88% of the cases. Beta-blockers were the most
      commonly prescribed medication (59%); 73% improved. CONCLUSIONS. Postural
      tachycardia syndrome was common in this large pediatric population, whereas
      orthostatic hypotension was infrequent. The symptomatic improvement in the
      majority bears an unclear relationship to treatment. Prospective studies are
      needed.

PMID- 21868598
TI  - Children with partial IgA deficiency: clinical characteristics observed in the
      pediatric rheumatology clinic.
AB  - Literature is lacking on partial IgA deficiency. In this study, the authors
      propose to describe the clinical manifestations of patients with partial IgA
      deficiency. Methods. The authors conducted a retrospective chart review of 13
      patients with partial IgA deficiency followed at the pediatric rheumatology
      clinic at Robert Wood Johnson Medical School. They looked for the presence of
      rashes, joint pain, joint swelling, and morning stiffness. The authors also
      examined charts for a history of frequent infections, allergies, and the presence
      of elevated antinuclear antibody. Results. Eleven out of the 13 patients
      complained of joint pain, joint swelling, or morning stiffness. Six patients
      carried a diagnosis of a definitive rheumatic disease. Four patients suffered
      from frequent infections and 2 patients reported allergies. Conclusion. Partial
      IgA deficiency appears to be associated with rheumatic diseases and complaints of
      joint pain, joint swelling, and morning stiffness. A larger study is needed to
      confirm these results.

PMID- 21868599
TI  - A term newborn male with retching.

PMID- 21868600
TI  - Rotavirus encephalitis with basal ganglia involvement in an 8-month-old infant.

PMID- 21868601
TI  - Determinants of cardiac disease in newly diagnosed patients with acromegaly:
      results of a 10 year survey study.
AB  - CONTEXT: The most frequent cause of death in acromegaly is cardiomyopathy.
      OBJECTIVE: To evaluate determinants of acromegalic cardiomyopathy. DESIGN:
      Observational, open, controlled, retrospective study. SUBJECTS: Two hundred and
      five patients with newly diagnosed active acromegaly (108 women and 97 men;
      median age 44 years) and 410 non-acromegalic subjects sex- and age-matched with
      the patients. MAIN OUTCOME MEASURES: Left ventricular (LV) mass index (LVMi),
      transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection
      fraction (LVEF) were measured by Doppler echocardiography to determine the
      prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role
      of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic
      and diastolic blood pressure, lipid profile and glucose tolerance in determining
      different features of the acromegalic cardiomyopathy was investigated. RESULTS:
      Compared with controls, the patients had lower E/A, LVEF, high-density
      lipoprotein (HDL)-cholesterol levels and higher LVMi, total- and low-density
      lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels,
      homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-beta. The
      relative risk to develop mild (odds ratio (OR)=1.67 (1.05-2.66); P=0.027) or
      severe hypertension (OR=1.58 (1.04-2.32); P=0.027), arrhythmias (OR=4.93 (1.74
      15.9); P=0.001), impaired fasting glucose/impaired glucose tolerance (OR=2.65
      (1.70-4.13); P<0.0001), diabetes (OR=2.14 (1.34-3.40); P=0.0009), LVH (OR=11.9
      (7.4-19.5); P<0.0001), diastolic (OR=3.32 (2.09-5.31); P<0.0001) and systolic
      dysfunction (OR=14.2 (6.95-32.2); P<0.0001), was higher in acromegaly. The most
      important predictor of LVH (t=2.4, P=0.02) and systolic dysfunction (t=-2.77,
      P=0.006) was disease duration and that of diastolic dysfunction was patient's age
      (t=-3.3, P=0.001). Patients with an estimated disease duration of >10 years had a
      relative risk to present cardiac complications three times higher than patients
      with estimated disease duration <=5 years. CONCLUSIONS: The prevalence of
      different features of cardiomyopathy is 3.3-14.2 times higher in the acromegalic
      than in the non-acromegalic population. The major determinant of cardiomyopathy
      is disease duration.

PMID- 21868602
TI  - A case of acromegaly (Greece, 7th century AD).
AB  - OBJECTIVE: To diagnose hormone-secreting pituitary adenoma in dry bones. DESIGN:
      We present here the case of a pathological skull from the Byzantine site of
      Eleutherna (Greece). METHODS: A complete anthropological and medical examination
      of the skull and the whole conserved skeleton was performed in the laboratory.
      RESULTS: All anatomical signs of acromegaly were present on this skull. More
      importantly, enlargement of the sella turcica clearly indicated the development
      of a macroadenoma, at the origin of the disease. CONCLUSIONS: This skeletal case,
      and other ancient ones are discussed, to better describe the history of the
      disease, and the possibilities of the diagnosis.

PMID- 21868603
TI  - Hybrid male sterility in rice is due to epistatic interactions with a pollen
      killer locus.
AB  - In intraspecific crosses between cultivated rice (Oryza sativa) subspecies indica
      and japonica, the hybrid male sterility gene S24 causes the selective abortion of
      male gametes carrying the japonica allele (S24-j) via an allelic interaction in
      the heterozygous hybrids. In this study, we first examined whether male sterility
      is due solely to the single locus S24. An analysis of near-isogenic lines (NIL
      F(1)) showed different phenotypes for S24 in different genetic backgrounds. The
      S24 heterozygote with the japonica genetic background showed male semisterility,
      but no sterility was found in heterozygotes with the indica background. This
      result indicates that S24 is regulated epistatically. A QTL analysis of a
      BC(2)F(1) population revealed a novel sterility locus that interacts with S24 and
      is found on rice chromosome 2. The locus was named Epistatic Factor for S24
      (EFS). Further genetic analyses revealed that S24 causes male sterility when in
      combination with the homozygous japonica EFS allele (efs-j). The results suggest
      that efs-j is a recessive sporophytic allele, while the indica allele (EFS-i) can
      dominantly counteract the pollen sterility caused by S24 heterozygosity. In
      summary, our results demonstrate that an additional epistatic locus is an
      essential element in the hybrid sterility caused by allelic interaction at a
      single locus in rice. This finding provides a significant contribution to our
      understanding of the complex molecular mechanisms underlying hybrid sterility and
      microsporogenesis.

PMID- 21868605
TI  - Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis
      elegans.
AB  - Gradients of acetylcholine can stimulate growth cone turning when applied to
      neurons grown in culture, and it has been suggested that acetylcholine could act
      as a guidance cue. However, the role acetylcholine plays in directing axon
      migrations in vivo is not clear. Here, we show that acetylcholine positively
      regulates signaling pathways that mediate axon responses to guidance cues in
      Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis,
      transportation, and secretion affect circumferential axon guidance of the AVM
      neuron and in these mutants exogenously supplied acetylcholine improves AVM
      circumferential axon guidance. These effects are not observed for the
      circumferential guidance of the DD and VD motor neuron axons, which are neighbors
      of the AVM axon. Circumferential guidance is directed by the UNC-6 (netrin) and
      SLT-1 (slit) extracellular cues, and exogenously supplied acetylcholine can
      improve AVM axon guidance in mutants when either UNC-6- or SLT-1-induced
      signaling is disrupted, but not when both signaling pathways are perturbed. Not
      in any of the mutants does exogenously supplied acetylcholine improve DD and VD
      axon guidance. The ability of acetylcholine to enhance AVM axon guidance only in
      the presence of either UNC-6 or SLT-1 indicates that acetylcholine potentiates
      UNC-6 and SLT-1 guidance activity, rather than acting itself as a guidance cue.
      Together, our results show that for specific neurons acetylcholine plays an
      important role in vivo as a modulator of axon responses to guidance cues.

PMID- 21868604
TI  - Wg signaling via Zw3 and mad restricts self-renewal of sensory organ precursor
      cells in Drosophila.
AB  - It is well known that the Dpp signal transducer Mad is activated by
      phosphorylation at its carboxy-terminus. The role of phosphorylation on other
      regions of Mad is not as well understood. Here we report that the phosphorylation
      of Mad in the linker region by the Wg antagonist Zw3 (homolog of vertebrate Gsk3
      beta) regulates the development of sensory organs in the anterior-dorsal quadrant
      of the wing. Proneural expression of Mad-RNA interference (RNAi) or a Mad
      transgene with its Zw3/Gsk3-beta phosphorylation sites mutated (MGM) generated
      wings with ectopic sensilla and chemosensory bristle duplications. Studies with
      pMad-Gsk (an antibody specific to Zw3/Gsk3-beta-phosphorylated Mad) in larval
      wing disks revealed that this phosphorylation event is Wg dependent (via an
      unconventional mechanism), is restricted to anterior-dorsal sensory organ
      precursors (SOP) expressing Senseless (Sens), and is always co-expressed with the
      mitotic marker phospho-histone3. Quantitative analysis in both Mad-RNAi and MGM
      larval wing disks revealed a significant increase in the number of Sens SOP. We
      conclude that the phosphorylation of Mad by Zw3 functions to prevent the self
      renewal of Sens SOP, perhaps facilitating their differentiation via asymmetric
      division. The conservation of Zw3/Gsk3-beta phosphorylation sites in vertebrate
      homologs of Mad (Smads) suggests that this pathway, the first transforming growth
      factor beta-independent role for any Smad protein, may be widely utilized for
      regulating mitosis during development.

PMID- 21868606
TI  - Combining markers into haplotypes can improve population structure inference.
AB  - High-throughput genotyping and sequencing technologies can generate dense sets of
      genetic markers for large numbers of individuals. For most species, these data
      will contain many markers in linkage disequilibrium (LD). To utilize such data
      for population structure inference, we investigate the use of haplotypes
      constructed by combining the alleles at single-nucleotide polymorphisms (SNPs).
      We introduce a statistic derived from information theory, the gain of
      informativeness for assignment (GIA), which quantifies the additional information
      for assigning individuals to populations using haplotype data compared to using
      individual loci separately. Using a two-loci-two-allele model, we demonstrate
      that combining markers in linkage equilibrium into haplotypes always leads to
      nonpositive GIA, suggesting that combining the two markers is not advantageous
      for ancestry inference. However, for loci in LD, GIA is often positive,
      suggesting that assignment can be improved by combining markers into haplotypes.
      Using GIA as a criterion for combining markers into haplotypes, we demonstrate
      for simulated data a significant improvement of assigning individuals to
      candidate populations. For the many cases that we investigate, incorrect
      assignment was reduced between 26% and 97% using haplotype data. For empirical
      data from French and German individuals, the incorrectly assigned individuals
      can, for example, be decreased by 73% using haplotypes. Our results can be useful
      for challenging population structure and assignment problems, in particular for
      studies where large-scale population-genomic data are available.

PMID- 21868607
TI  - Cost of adaptation and fitness effects of beneficial mutations in Pseudomonas
      fluorescens.
AB  - Adaptations are constructed through the sequential substitution of beneficial
      mutations by natural selection. However, the rarity of beneficial mutations has
      precluded efforts to describe even their most basic properties. Do beneficial
      mutations typically confer small or large fitness gains? Are their fitness
      effects environment specific, or are they broadly beneficial across a range of
      environments? To answer these questions, we used two subsets (n = 18 and n = 63)
      of a large library of mutants carrying antibiotic resistance mutations in the
      bacterium Pseudomonas fluorescens whose fitness, along with the antibiotic
      sensitive ancestor, was assayed across 95 novel environments differing in the
      carbon source available for growth. We explore patterns of genotype-by
      environment (G * E) interactions and ecological specialization among the 18
      mutants initially found superior to the sensitive ancestor in one environment. We
      find that G * E is remarkably similar between the two sets of mutants and that
      beneficial mutants are not typically associated with large costs of adaptation.
      Fitness effects among beneficial mutants depart from a strict exponential
      distribution: they assume a variety of shapes that are often roughly L shaped but
      always right truncated. Distributions of (beneficial) fitness effects predicted
      by a landscape model assuming multiple traits underlying fitness and a single
      optimum often provide a good description of the empirical distributions in our
      data. Simulations of data sets containing a mixture of single and double mutants
      under this landscape show that inferences about the distribution of fitness
      effects of beneficial mutants is quite robust to contamination by second-site
      mutations.

PMID- 21868608
TI  - Complex mechanisms regulate developmental expression of the matA (HMG) mating
      type gene in homothallic Aspergillus nidulans.
AB  - Sexual reproduction is a fundamental developmental process that allows for
      genetic diversity through the control of zygote formation, recombination, and
      gametogenesis. The correct regulation of these events is paramount. Sexual
      reproduction in filamentous fungi, including mating strategy (self
      fertilization/homothallism or outcrossing/heterothallism), is determined by the
      expression of mating type genes at mat loci. Aspergillus nidulans matA encodes a
      critical regulator that is a fungal ortholog of the hSRY/SOX9 HMG box proteins.
      In contrast to well-studied outcrossing systems, the molecular basis of
      homothallism and role of mating type genes during a self-fertile sexual cycle
      remain largely unknown. In this study the genetic model organism, A. nidulans,
      has been used to investigate the regulation and molecular functions of the matA
      mating type gene in a homothallic system. Our data demonstrate that complex
      regulatory mechanisms underlie functional matA expression during self
      fertilization and sexual reproduction in A. nidulans. matA expression is
      suppressed in vegetative hyphae and is progressively derepressed during the
      sexual cycle. Elevated levels of matA transcript are required for differentiation
      of fruiting bodies, karyogamy, meiosis, and efficient formation of meiotic
      progeny. matA expression is driven from both initiator (Inr) and novel promoter
      elements that are tightly developmentally regulated by position-dependent and
      position-independent mechanisms. Deletion of an upstream silencing element, matA
      SE, results in derepressed expression from wild-type (wt) promoter elements and
      activation of an additional promoter. These studies provide novel insights into
      the molecular basis of homothallism in fungi and genetic regulation of sexual
      reproduction in eukaryotes.

PMID- 21868609
TI  - Cell architecture: surrounding muscle cells shape gland cell morphology in the
      Caenorhabditis elegans pharynx.
AB  - The acquisition and maintenance of shape is critical for the normal function of
      most cells. Here we investigate the morphology of the pharyngeal glands of
      Caenorhabditis elegans. These unicellular glands have long cellular processes
      that extend discrete lengths through the pharyngeal musculature and terminate at
      ducts connected to the pharyngeal lumen. From a genetic screen we identified
      several mutants that affect pharyngeal gland morphology. The most severe such
      mutant is an allele of sma-1, which encodes a beta-spectrin required for
      embryonic elongation, including elongation of the pharynx. In sma-1 mutants,
      gland projections form normally but become increasingly abnormal over time,
      acquiring additional branches, outgrowths, and swelling, suggestive of
      hypertrophy. Rather than acting in pharyngeal glands, sma-1 functions in the
      surrounding musculature, suggesting that pharyngeal muscles play a critical role
      in maintenance of gland morphology by restricting their growth, and analysis of
      other mutants known to affect pharyngeal muscles supports this hypothesis. We
      suggest that gland morphology is maintained by a balance of forces from the
      muscles and the glands.

PMID- 21868610
TI  - Successful treatment of long-term, poststroke, upper-limb spasticity with
      onabotulinumtoxinA.
AB  - BACKGROUND AND PURPOSE: Poststroke spasticity often negatively affects functional
      activities and daily living and frequently is accompanied by pain, abnormal limb
      postures, and contractures. The purpose of this case report is to describe the
      long-term benefit of botulinum toxin A in a patient with poststroke spasticity.
      CASE DESCRIPTION: A 35-year-old woman with poststroke upper-limb spasticity who
      had lost function in her left hand was treated with onabotulinumtoxinA and
      physical therapy. Over 25 months, the patient received a physical therapy and
      occupational therapy program and received onabotulinumtoxinA injections into
      muscles of the left hand and arm, significantly reducing tone and facilitating
      recovery of function. Practical assessments, the Ashworth Scale, and
      electrophysiology were used to measure changes over time. No functional scales or
      dexterity scales were used to measure changes. OUTCOMES: OnabotulinumtoxinA
      injections were discontinued when treatment goals were attained, and no further
      improvements were achieved. After more than 21/2 years without further
      onabotulinumtoxinA treatments, the patient maintained range of motion and some
      functional use and dexterity in her left hand. DISCUSSION: This case report
      illustrates the efficacy and long-term benefit of onabotulinumtoxinA, combined
      with physical therapy and occupational therapy, in the successful treatment of
      poststroke spasticity.

PMID- 21868611
TI  - Complete decongestive physical therapy in a patient with secondary lymphedema due
      to orthopedic trauma and surgery of the lower extremity.
AB  - BACKGROUND AND PURPOSE: This case report describes a patient who developed lower
      extremity lymphedema secondary to orthopedic trauma and surgery and reports the
      response to complete decongestive physical therapy (CDP), with 8 treatment
      sessions over 3 months. CASE DESCRIPTION: The patient was a 56-year-old man who
      sustained a right ankle displaced fibular fracture, underwent open reduction
      internal fixation surgery 12 days later, and developed lymphedema 4 months
      postinjury. The patient's impairments of the right lower extremity included
      increased girth, decreased ankle range of motion, and increased pain. Due to
      these impairments and the inability to fit into normal footwear, the patient
      limited activities such as ambulating long distances and climbing stairs. This
      limited activity restricted him from participating in his normal lifestyle
      activities such as walking his dog in the community and performing all necessary
      work duties. OUTCOMES: Using the truncated cone formula to measure limb volume,
      the limb volume of the right (involved) lower extremity decreased 368 mL as a
      result of CDP. The percentage of difference in limb volume between the right and
      left lower extremities at the initial examination was 9%, and it was reduced to
      less than 1% at discharge. He was independent with his home program in order to
      maintain the results of therapy. DISCUSSION: Physical therapist management of
      secondary lymphedema due to orthopedic trauma and surgery of the lower extremity
      was effective in decreasing circumferential girth measurements and decreasing
      limb volume, thereby improving gait and allowing the patient to fit into his work
      and leisure shoes. The patient reported improvement in his ability to perform all
      work activities, and he returned to his prior level of participation in the
      community.

PMID- 21868612
TI  - HOBOE (Head-of-Bed Optimization of Elevation) Study: association of higher angle
      with reduced cerebral blood flow velocity in acute ischemic stroke.
AB  - BACKGROUND: Cerebral autoregulation can be impaired after ischemic stroke, with
      potential adverse effects on cerebral blood flow during early rehabilitation.
      OBJECTIVE: The objective of this study was to assess changes in cerebral blood
      flow velocity with orthostatic variation at 24 hours after stroke. DESIGN: This
      investigation was an observational study comparing mean flow velocities (MFVs) at
      30, 15, and 0 degrees of elevation of the head of the bed (HOB). METHODS: Eight
      participants underwent bilateral middle cerebral artery (MCA) transcranial
      Doppler monitoring during orthostatic variation at 24 hours after ischemic
      stroke. Computed tomography angiography separated participants into recanalized
      (artery completely reopened) and incompletely recanalized groups. Friedman tests
      were used to determine MFVs at the various HOB angles. Mann-Whitney U tests were
      used to compare the change in MFV (from 30 degrees  to 0 degrees ) between groups
      and between hemispheres within groups. RESULTS: For stroke-affected MCAs in the
      incompletely recanalized group, MFVs differed at the various HOB angles (30
      degrees : median MFV=51.5 cm/s, interquartile range [IQR]=33.0 to 103.8; 15
      degrees : median MFV=55.5 cm/s, IQR=34.0 to 117.5; 0 degrees : median MFV=85.0
      cm/s, IQR=58.8 to 127.0); there were no significant differences for other MCAs.
      For stroke-affected MCAs in the incompletely recanalized group, MFVs increased
      with a change in the HOB angle from 30 degrees to 0 degrees by a median of 26.0
      cm/s (IQR=21.3 to 35.3); there were no significant changes in the recanalized
      group (-3.5 cm/s, IQR=-12.3 to 0.8). The changes in MFV with a change in the HOB
      angle from 30 degrees to 0 degrees differed between hemispheres in the
      incompletely recanalized group but not in the recanalized group. LIMITATIONS:
      Generalizability was limited by sample size. CONCLUSIONS: The incompletely
      recanalized group showed changes in MFVs at various HOB angles, suggesting that
      cerebral blood flow in this group may be sensitive to orthostatic variation,
      whereas the recanalized group maintained stable blood flow velocities.

PMID- 21868613
TI  - Balance assessment practices and use of standardized balance measures among
      Ontario physical therapists.
AB  - BACKGROUND: Balance impairment is a significant problem for older adults, as it
      can influence daily functioning. Treating balance impairment in this population
      is a major focus of physical therapist practice. OBJECTIVE: The purpose of this
      study was to document current practices in clinical balance assessment and
      compare components of balance assessed and measures used across practice areas
      among physical therapists. DESIGN: This was a cross-sectional study. METHODS: A
      survey questionnaire was mailed to 1,000 practicing physical therapists in
      Ontario, Canada. RESULTS: Three hundred sixty-nine individuals completed the
      survey questionnaire. More than 80% of respondents reported that they regularly
      (more than 60% of the time) assessed postural alignment, static and dynamic
      stability, functional balance, and underlying motor systems. Underlying sensory
      systems, cognitive contributions to balance, and reactive control were regularly
      assessed by 59.6%, 55.0%, and 41.2% of the respondents, respectively. The
      standardized measures regularly used by the most respondents were the single-leg
      stance test (79.1%), the Berg Balance Scale (45.0%), and the Timed "Up & Go" Test
      (27.6%). There was considerable variation in the components of balance assessed
      and measures used by respondents treating individuals in the orthopedic,
      neurologic, geriatric, and general rehabilitation populations. LIMITATIONS: The
      survey provides quantitative data about what is done to assess balance, but does
      not explain the factors influencing current practice. CONCLUSIONS: Many important
      components of balance and standardized measures are regularly used by physical
      therapists to assess balance. Further research, however, is needed to understand
      the factors contributing to the relatively lower rates of assessing reactive
      control, the component of balance most directly responsible for avoiding a fall.

PMID- 21868614
TI  - A case report of a student-led pro bono clinic: a proposed model for meeting
      student and community needs in a sustainable manner.
AB  - BACKGROUND AND PURPOSE: The Chester Community Physical Therapy Clinic (clinic) is
      a student-led pro bono clinic that provides physical therapy services to
      uninsured and underinsured community members. The purposes of this administrative
      case report are to describe the creation and implementation of a student-led pro
      bono clinic model designed to meet student and community needs and to consider
      its potential for sustainability. CASE DESCRIPTION: Students and faculty created
      an organizational model with a Student Board at the center of clinic leadership.
      A Faculty Board provides oversight to the Student Board. State-licensed faculty
      and alumni provide the direct supervision of the treating student physical
      therapists. Evaluation of our clinic model was performed using strategies for the
      creation of sustainable community engagement initiatives. OUTCOMES: This model of
      a student-led pro bono clinic has elements of all 8 steps to sustainable
      community engagement. The model of a student-led pro bono clinic is feasible and
      sustainable. DISCUSSION: A student-led pro bono clinic serving the physical
      therapy needs of the uninsured and underinsured residents in an urban community
      presents an innovative educational and leadership development opportunity for
      students and alumni as well as partnership opportunities with the community.

PMID- 21868615
TI  - Phenotype and outcome in hereditary tubulointerstitial nephritis secondary to
      UMOD mutations.
AB  - BACKGROUND: UMOD mutations cause familial juvenile hyperuricemic nephropathy
      (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are
      nonspecific. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed cases of
      UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris,
      France) and of Universite Catholique de Louvain (Brussels, Belgium). We also
      analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds
      for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these
      parameters were analyzed in 1097 patients with various renal diseases and renal
      function levels. RESULTS: Thirty-seven distinct UMOD mutations were found in 109
      patients from 45 families, all in exon 4 or 5 except for three novel mutations in
      exon 8. Median renal survival was 54 years. The type of mutation had a modest
      effect on renal survival, and intrafamilial variability was high. Detailed data
      available in 70 patients showed renal cysts in 24 (34.3%) of nonspecific
      localization in most patients. Uricemia was >75th percentile in 31 (71.4%) of 42
      patients not under dialysis or allopurinol therapy. UAEF (n = 27) was <75th
      percentile in 70.4%. Among 136 probands with MCKD/FJHN phenotype, UMOD mutation
      was found in 24 (17.8%). Phenotype was not accurately predictive of UMOD
      mutation. Six probands had HNF1B mutations. CONCLUSIONS: Hyperuricemia
      disproportionate to renal function represents the hallmark of renal disease
      caused by UMOD mutation. Renal survival is highly variable in patients with UMOD
      mutation. Our data also add novel insights into the interpretation of uricemia
      and UAEF in patients with chronic kidney diseases.

PMID- 21868616
TI  - Uric acid levels and all-cause and cardiovascular mortality in the hemodialysis
      population.
AB  - BACKGROUND AND OBJECTIVES: Hyperuricemia is associated with hypertension,
      coronary artery disease, and chronic kidney disease. However, there are no
      specific data on the relationship of uric acid to cardiovascular disease in the
      chronic hemodialysis setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data
      from 5827 patients on chronic hemodialysis from six countries affiliated with the
      Dialysis Outcomes and Practice Patterns Study (DOPPS) were analyzed. All
      laboratory data were based upon the initial cross-section of patients in DOPPS I
      and II. Cox regression was used to calculate the hazard ratio (HR) of all-cause
      and cardiovascular (CV) mortality with adjustments for case-mix including 14
      classes of comorbidity. RESULTS: There were no clinically significant differences
      in baseline characteristics between those who had measured uric acid (n = 4637)
      and those who did not (n = 1190). Uric acid level was associated with lower all
      cause mortality (HR: 0.95, 95% confidence interval [CI]: 0.90 to 1.00 per 1 mg/dl
      higher uric acid level) and CV mortality (HR: 0.92, 95% CI: 0.86 to 0.99). When
      analyzed as a dichotomous variable, the adjusted HR at uric acid <=8.2 mg/dl
      compared with >8.2 mg/dl was 1.24 (95% CI: 1.03 to 1.49) for all-cause mortality
      and 1.54 (95% CI: 1.15 to 2.07) for CV mortality. CONCLUSIONS: Higher uric acid
      levels were associated with lower risk of all-cause and CV mortality in the
      hemodialysis population. These results are in contrast to the association of
      hyperuricemia with higher cardiovascular risk in the general population and
      should be the subject of further research.

PMID- 21868617
TI  - C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Measurement of C-reactive protein (CRP) levels remains
      uncommon in North America, although it is now routine in many countries. Using
      Dialysis Outcomes and Practice Patterns Study data, our primary aim was to
      evaluate the value of CRP for predicting mortality when measured along with other
      common inflammatory biomarkers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      studied 5061 prevalent hemodialysis patients from 2005 to 2008 in 140 facilities
      routinely measuring CRP in 10 countries. The association of CRP with mortality
      was evaluated using Cox regression. Prediction of 1-year mortality was assessed
      in logistic regression models with differing adjustment variables. RESULTS:
      Median baseline CRP was lower in Japan (1.0 mg/L) than other countries (6.0
      mg/L). CRP was positively, monotonically associated with mortality. No threshold
      below which mortality rate leveled off was identified. In prediction models, CRP
      performance was comparable with albumin and exceeded ferritin and white blood
      cell (WBC) count based on measures of model discrimination (c-statistics, net
      reclassification improvement [NRI]) and global model fit (generalized R(2)). The
      primary analysis included age, gender, diabetes, catheter use, and the four
      inflammatory markers (omitting one at a time). Specifying NRI >=5% as appropriate
      reclassification of predicted mortality risk, NRI for CRP was 12.8% compared with
      10.3% for albumin, 0.8% for ferritin, and <0.1% for WBC. CONCLUSIONS: These
      findings demonstrate the value of measuring CRP in addition to standard
      inflammatory biomarkers to improve mortality prediction in hemodialysis patients.
      Future studies are indicated to identify interventions that lower CRP and to
      identify whether they improve clinical outcomes.

PMID- 21868618
TI  - Improvement in the renal prognosis in nephropathic cystinosis.
AB  - BACKGROUND AND OBJECTIVES: Nephropathic cystinosis (NC) is an autosomal recessive
      disorder occurring in one to two per 100,000 newborns. Because of the rarity of
      NC, long-term outcome data are scarce. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: 245 NC patients from 18 countries provided data to the ESPN/ERA
      EDTA registry. We matched NC patients on renal replacement therapy (RRT) to non
      NC children on RRT. RESULTS: Between 1979 and 2008, mean age at the start of RRT
      among NC children increased by 0.15 year per calendar year (95% confidence
      interval, 0.10 to 0.21) from 8.8 to 12.7 years, whereas we did not observe this
      in non-NC children. Five-year survival after the start of RRT improved in NC
      patients from 86.1% (before 1990) to 100% (since 2000) as compared with the
      control population (89.6% and 94.0%). NC patients received a renal allograft more
      often (relative risk, 1.09; 95% confidence interval, 1.00 to 1.17) as compared
      with matched RRT children, and 5-year graft survival was better (94.0% versus
      84.0%). NC dialysis patients were less often hypertensive than non-NC children
      matched for age, country, and dialysis modality (42.7% versus 51.7%) and had
      lower parathyroid hormone levels (median, 56 versus 140 pg/ml). Although height
      at start of RRT slightly improved during the past decade, children with NC
      remained significantly shorter than non-NC children at the start of RRT.
      CONCLUSIONS: We demonstrated improved survival of the renal function as well as
      better patient and graft survival after the start of RRT in a large European
      cohort of NC patients over the last two decades.

PMID- 21868619
TI  - The depth of the olfactory sulcus is an indicator of congenital anosmia.
AB  - BACKGROUND AND PURPOSE: In congenital anosmia, the OB and OT can be aplastic or
      hypoplastic. In clinical routine, these are sometimes difficult to assess. We
      thus wanted to investigate morphologic differences of the OS in patients with IA
      since birth or early childhood in comparison with controls, to investigate
      whether there is a depth of OS that is predictive of IA. MATERIALS AND METHODS:
      Within the context of a 2-center study, we investigated 36 patients with IA in
      comparison with 70 controls. MR imaging was performed with a standard quadrature
      head coil (1.5T; T1- and T2-weighted spin-echo sequences were used on the coronal
      plane). We assessed the depth of OS in the PPTE. RESULTS: Looking at the depth of
      the OS in the PPTE, we found that patients with IA had a significantly smaller OS
      compared with controls (P < .001). None of the healthy controls exhibited a depth
      of <8 mm. In patients with IA, 10 had an OS deeper than 8 mm, while 26 had an OS
      smaller than 8 mm. Thus, a depth of the OS less than 8 mm clearly indicates IA,
      with a specificity of 1 and a sensitivity of 0.72. CONCLUSIONS: In IA, the depth
      of the OS in the PPTE is a useful clinical indicator. Indeed, if it is <=8 mm, it
      clearly indicates IA, with a specificity of 1.

PMID- 21868620
TI  - Carotid plaque enhancement and symptom correlations: an evaluation by using
      multidetector row CT angiography.
AB  - BACKGROUND AND PURPOSE: The identification of plaque characteristics that
      determine its vulnerability is extremely important. The purpose of this work was
      to evaluate CPE after administration of contrast material and to assess whether
      there is a statistical association between CPE and cerebrovascular symptoms.
      MATERIALS AND METHODS: Ninety-seven consecutive patients (69 men, 28 women; mean
      age, 62 years; age range, 39-82 years), studied by using an MDCT scanner, were
      retrospectively analyzed. Examinations were performed before and after
      administration of contrast medium. Plaque enhancement was analyzed, and the
      obtained data were compared with the patient's symptoms. Patients were classified
      as symptomatic (TIA or stroke with a temporal window of 6 months) or asymptomatic
      according to neurologic assessment and the TOAST criteria. The ROC curve and Az
      were calculated, and multiple logistic regression analysis was performed.
      RESULTS: Thirty-nine patients were excluded because they had calcified plaques
      (40.2%). CPE was observed in 74% of the remaining 58 patients. A statistically
      significant difference was observed between symptomatic and asymptomatic patients
      for the presence of CPE (P = .0013; OR = 7.5). Moreover, we observed that CPE was
      higher in fatty plaques (P = .035) than in mixed ones and more frequent in the
      former (P = .0119). The ROC curve demonstrated that a threshold of 15 HU is
      associated with a specificity and sensitivity of 83.33% and 76.47%, respectively.
      Multiple logistic regression showed that CPE and symptoms are associated (P =
      .0315). CONCLUSIONS: The results of our study suggest that for noncalcified
      carotid plaques, the presence of CPE is associated with cerebrovascular symptoms.
      Fatty plaques are more likely to have CPE compared with mixed plaques.

PMID- 21868621
TI  - What is the RUC?
AB  - We describe a crucial but little-known constituent of the Medicare payment
      system.

PMID- 21868622
TI  - Cerebral blood flow alterations in pain-processing regions of patients with
      fibromyalgia using perfusion MR imaging.
AB  - BACKGROUND AND PURPOSE: Widespread pain sensitivity in patients with FM suggests
      a CNS processing problem. The purpose of this study was to assess alterations in
      perfusion as measured by DSC in a number of brain regions implicated in pain
      processing between patients with FM and healthy controls. MATERIALS AND METHODS:
      Twenty-one patients with FM and 27 healthy controls underwent conventional MR
      imaging and DSC. For DSC, 12 regions of interest were placed in brain regions
      previously implicated in pain processing. rCBF values were calculated for each
      region of interest. Subjects answered mood/pain coping questionnaires and
      underwent clinical/experimental pain assessment. RESULTS: There were significant
      correlations between the thalamic rCBF values and the pain-control beliefs of FM
      subjects. The strength of the relationship between clinical pain measures and
      thalamic rCBF values increased after adjusting for pain-control beliefs. There
      was a significantly different distribution pattern of rCBF values across various
      brain regions between the FM group and the healthy controls. There was a lower
      degree of correlation in the FM group between the thalamic rCBF values and the
      other brain regions relative to the healthy controls. CONCLUSIONS: Significant
      correlations were found between thalamic rCBF values and pain belief values.
      These data suggest that there are baseline alterations of brain perfusion in
      patients with FM. rCBF values of the thalami exhibited lower correlations with
      respect to other brain regions thought to be involved in pain processing compared
      with those in healthy controls.

PMID- 21868623
TI  - Cerebral ischemia complicating intracranial aneurysm: a warning sign of imminent
      rupture?
AB  - BACKGROUND AND PURPOSE: Patients harboring nongiant cerebral aneurysms may rarely
      present with an ischemic infarct distal to the aneurysm. The aim of this case
      series was to report clinical and radiologic characteristics of these patients,
      their management, and outcome. MATERIALS AND METHODS: We undertook a single
      center retrospective analysis of consecutive patients admitted during an 8-year
      period with an acute ischemic stroke revealing an unruptured nongiant (<25 mm)
      sacciform intracranial aneurysm. Clinical, radiologic, therapeutic, and follow-up
      data were analyzed. RESULTS: Nine patients were included. The mean size of
      aneurysms was 9.6 +/- 6 mm, and 5 were partially or totally thrombosed. Two
      patients had a fatal SAH within 3 days after stroke-symptom onset, whereas
      asymptomatic meningeal bleeding was diagnosed or suspected in 2 others. Most of
      the patients with unthrombosed aneurysms were successfully treated by
      endovascular coiling in the acute phase. Thrombosed aneurysms were usually
      treated with antithrombotics, and most recanalized secondarily, requiring
      endovascular treatment or surgical obliteration. No recurrence of an ischemic
      event or SAH was observed during the 31 +/- 12 months of follow-up (from 4 to 53
      months). CONCLUSIONS: In this single-center series, the frequency of early SAH in
      patients with ischemic stroke distal to an unruptured intracranial aneurysm was
      high. Acute management should be undertaken with care regarding antithrombotic
      use, and early endovascular coiling should be considered.

PMID- 21868624
TI  - G protein-coupled receptors in human fat taste perception.
AB  - In contrast to carbohydrates and proteins, which are detected by specialized
      taste receptors in the forms of their respective building blocks, sugars, and L
      amino acids, the third macronutrient, lipids, has until now not been associated
      with gustatory receptors. Instead, the recognition of fat stimuli was believed to
      rely mostly on textural, olfactory, and postingestive cues. During the recent
      years, however, research done mainly in rodent models revealed an additional
      gustatory component for the detection of long-chain fatty acids (LCFAs), the main
      taste-activating component of lipids. Concomitantly, a number of candidate fat
      taste receptors were proposed to be involved in rodent's gustatory fatty acid
      perception. Compared with rodent models, much less is known about human fat
      taste. In order to investigate the ability of the human gustatory system to
      respond to fat components, we performed sensory experiments with fatty acids of
      different chain lengths and derivatives thereof. We found that our panelists
      discriminated a "fatty" and an irritant "scratchy" taste component, with the
      "fatty" percept restricted to LCFAs. Using functional calcium-imaging experiments
      with the human orthologs of mouse candidate fat receptors belonging to the G
      protein-coupled receptor family, we correlated human sensory data with receptor
      properties characterized in vitro. We demonstrated that the pharmacological
      activation profile of human GPR40 and GPR120, 2 LCFA-specific receptors
      associated with gustatory fat perception in rodents, is inconsistent with the
      "scratchy" sensation of human subjects and more consistent with the percept
      described as "fatty." Expression analysis of GPR40 and GPR120 in human gustatory
      tissues revealed that, while the GPR40 gene is not expressed, GPR120 is detected
      in gustatory and nongustatory epithelia. On a cellular level, we found GPR120
      mRNA and protein in taste buds as well as in the surrounding epithelial cells. We
      conclude that GPR120 may indeed participate in human gustatory fatty acid
      perception.

PMID- 21868625
TI  - Raman's "effect" on molecular imaging.
AB  - Raman spectroscopy is an optical technique that offers unsurpassed sensitivity
      and multiplexing capabilities to the field of molecular imaging. In the past,
      Raman spectroscopy had predominantly been used as an analytic tool for routine
      chemical analysis, but more recently, researchers have been able to harness its
      unique properties for imaging and spectral analysis of molecular interactions in
      cell populations and preclinical animal models. Additionally, researchers have
      already begun to translate this optical technique into a novel clinical
      diagnostic tool using various endoscopic strategies.

PMID- 21868626
TI  - A reservoir of ionized gas in the galactic halo to sustain star formation in the
      Milky Way.
AB  - Without a source of new gas, our Galaxy would exhaust its supply of gas through
      the formation of stars. Ionized gas clouds observed at high velocity may be a
      reservoir of such gas, but their distances are key for placing them in the
      galactic halo and unraveling their role. We have used the Hubble Space Telescope
      to blindly search for ionized high-velocity clouds (iHVCs) in the foreground of
      galactic stars. We show that iHVCs with 90 <= |v(LSR)| ? 170 kilometers per
      second (where v(LSR) is the velocity in the local standard of rest frame) are
      within one galactic radius of the Sun and have enough mass to maintain star
      formation, whereas iHVCs with |v(LSR)| ? 170 kilometers per second are at larger
      distances. These may be the next wave of infalling material.

PMID- 21868627
TI  - Promoting the Middle East peace process by changing beliefs about group
      malleability.
AB  - Four studies showed that beliefs about whether groups have a malleable versus
      fixed nature affected intergroup attitudes and willingness to compromise for
      peace. Using a nationwide sample (N = 500) of Israeli Jews, the first study
      showed that a belief that groups were malleable predicted positive attitudes
      toward Palestinians, which in turn predicted willingness to compromise. In the
      remaining three studies, experimentally inducing malleable versus fixed beliefs
      about groups among Israeli Jews (N = 76), Palestinian citizens of Israel (N =
      59), and Palestinians in the West Bank (N = 53)--without mentioning the adversary
      -led to more positive attitudes toward the outgroup and, in turn, increased
      willingness to compromise for peace.

PMID- 21868628
TI  - MED12, the mediator complex subunit 12 gene, is mutated at high frequency in
      uterine leiomyomas.
AB  - Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women
      worldwide and that can cause considerable morbidity. To study the genetic basis
      of this tumor type, we examined 18 uterine leiomyomas derived from 17 different
      patients by exome sequencing and identified tumor-specific mutations in the
      mediator complex subunit 12 (MED12) gene in 10. Through analysis of 207
      additional tumors, we determined that MED12 is altered in 70% (159 of 225) of
      tumors from a total of 80 patients. The Mediator complex is a 26-subunit
      transcriptional regulator that bridges DNA regulatory sequences to the RNA
      polymerase II initiation complex. All mutations resided in exon 2, suggesting
      that aberrant function of this region of MED12 contributes to tumorigenesis.

PMID- 21868629
TI  - Transformation of a star into a planet in a millisecond pulsar binary.
AB  - Millisecond pulsars are thought to be neutron stars that have been spun-up by
      accretion of matter from a binary companion. Although most are in binary systems,
      some 30% are solitary, and their origin is therefore mysterious. PSR J1719-1438,
      a 5.7-millisecond pulsar, was detected in a recent survey with the Parkes 64
      meter radio telescope. We show that this pulsar is in a binary system with an
      orbital period of 2.2 hours. The mass of its companion is near that of Jupiter,
      but its minimum density of 23 grams per cubic centimeter suggests that it may be
      an ultralow-mass carbon white dwarf. This system may thus have once been an
      ultracompact low-mass x-ray binary, where the companion narrowly avoided complete
      destruction.

PMID- 21868631
TI  - Liver-brain inflammation axis.
AB  - It is becoming increasingly evident that peripheral organ-centered inflammatory
      diseases, including chronic inflammatory liver diseases, are associated with
      changes in central neural transmission that result in alterations in behavior.
      These behavioral changes include sickness behaviors, such as fatigue, cognitive
      dysfunction, mood disorders, and sleep disturbances. While such behaviors have a
      significant impact on quality of life, the changes within the brain and the
      communication pathways between the liver and the brain that give rise to changes
      in central neural activity are not fully understood. Traditionally, neural and
      humoral communication pathways have been described, with the three cytokines
      TNFalpha, IL-1beta, and IL-6 receiving the most attention in mediating
      communication between the periphery and the brain, in the setting of peripheral
      inflammation. However, more recently, we described an immune-mediated
      communication pathway in experimentally induced liver inflammation whereby, in
      response to activation of resident immune cells in the brain (i.e., the
      microglia), peripheral circulating monocytes transmigrate into the brain, leading
      to development of sickness behaviors. These signaling pathways drive changes in
      behavior by altering central neurotransmitter systems. Specifically, changes in
      serotonergic and corticotropin-releasing hormone neurotransmission have been
      demonstrated and implicated in liver inflammation-associated sickness behaviors.
      Understanding how the liver communicates with the brain in the setting of chronic
      inflammatory liver diseases will help delineate novel therapeutic targets that
      can reduce the burden of symptoms in patients with liver disease.

PMID- 21868630
TI  - The shaping of modern human immune systems by multiregional admixture with
      archaic humans.
AB  - Whole genome comparisons identified introgression from archaic to modern humans.
      Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital
      immune system components subject to strong balancing selection, shows how modern
      humans acquired the HLA-B*73 allele in west Asia through admixture with archaic
      humans called Denisovans, a likely sister group to the Neandertals. Virtual
      genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes
      carrying functionally distinctive alleles that have introgressed into modern
      Eurasian and Oceanian populations. These alleles, of which several encode unique
      or strong ligands for natural killer cell receptors, now represent more than half
      the HLA alleles of modern Eurasians and also appear to have been later introduced
      into Africans. Thus, adaptive introgression of archaic alleles has significantly
      shaped modern human immune systems.

PMID- 21868632
TI  - Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol
      feeding/exposure.
AB  - Thiamin is important for normal function of pancreatic acinar cells, but little
      is known about its mechanism of uptake and about the effect of chronic alcohol
      use on the process. We addressed these issues using freshly isolated rat primary
      and rat-derived cultured AR42J pancreatic acinar cells as models. Results showed
      thiamin uptake by both primary and cultured AR42J pancreatic acinar cells to be
      via a specific carrier-mediated mechanism and that both of the thiamin
      transporters 1 and 2 (THTR-1 and THTR-2) are expressed in these cells. Chronic
      alcohol feeding of rats was found to lead to a significant inhibition of carrier
      mediated thiamin uptake by pancreatic acinar cells and was associated with a
      significant reduction in level of expression of THTR-1 and THTR-2 at the protein
      and mRNA levels. Chronic exposure (96 h) of AR42J cells to alcohol also led to a
      significant decreased carrier-mediated thiamin uptake, an effect that was
      associated with a significant decrease in the activity of the human SLC19A2 and
      SLC19A3 promoters expressed in these cells. We also examined the effect of
      chronic alcohol feeding of rats on level of expression of key thiamin
      metabolizing enzymes (thiamin phosphokinase and thiamin pyrophosphatase) as well
      as on level of expression of the mitochondrial thiamin pyrophosphate transporter
      of pancreatic acinar cells and observed a significant inhibition in all these
      parameters. These results demonstrate for the first time that thiamin uptake by
      pancreatic acinar cells is via a carrier-mediated process and that both the THTR
      1 as well as THTR-2 are expressed in these cells. Also, chronic alcohol
      feeding/exposure inhibits thiamin uptake process and the inhibition is, at least
      in part, being exerted at the transcriptional level. Furthermore, chronic alcohol
      feeding also negatively impacts intracellular parameters of thiamin metabolism in
      pancreatic acinar cells.

PMID- 21868634
TI  - Confocal laser endomicroscopy in dynamic evaluation of hepatic apoptosis in vivo.

PMID- 21868633
TI  - Characteristics of Kcnn4 channels in the apical membranes of an intestinal
      epithelial cell line.
AB  - Intermediate-conductance K(+) (Kcnn4) channels in the apical and basolateral
      membranes of epithelial cells play important roles in agonist-induced fluid
      secretion in intestine and colon. Basolateral Kcnn4 channels have been well
      characterized in situ using patch-clamp methods, but the investigation of Kcnn4
      channels in apical membranes in situ has been hampered by a layer of mucus that
      prevents seal formation. In the present study, we used patch-clamp methods to
      characterize Kcnn4 channels in the apical membrane of IEC-18 cells, a cell line
      derived from rat small intestine. A monolayer of IEC-18 cells grown on a
      permeable support is devoid of mucus, and tight junctions enable selective access
      to the apical membrane. In inside-out patches, Ca(2+)-dependent K(+) channels
      observed with iberiotoxin (a Kcnma1/large-conductance, Ca(2+)-activated K(+)
      channel blocker) and apamin (a Kcnn1-3/small-conductance, Ca(2+)-activated K(+)
      channel blocker) present in the pipette solution exhibited a single-channel
      conductance of 31 pS with inward rectification. The currents were reversibly
      blocked by TRAM-34 (a Kcnn4 blocker) with an IC(50) of 8.7 +/- 2.0 MUM. The
      channels were not observed when charybdotoxin, a peptide inhibitor of Kcnn4
      channels, was added to the pipette solution. TRAM-34 was less potent in
      inhibiting Kcnn4 channels in patches from apical membranes than in patches from
      basolateral membranes, which was consistent with a preferential expression of
      Kcnn4c and Kcnn4b isoforms in apical and basolateral membranes, respectively. The
      expression of both isoforms in IEC-18 cells was confirmed by RT-PCR and Western
      blot analyses. This is the first characterization of Kcnn4 channels in the apical
      membrane of intestinal epithelial cells.

PMID- 21868635
TI  - The laxative effect of bisacodyl is attributable to decreased aquaporin-3
      expression in the colon induced by increased PGE2 secretion from macrophages.
AB  - The purpose of this study was to investigate the role of aquaporin3 (AQP3) in the
      colon in the laxative effect of bisacodyl. After oral administration of bisacodyl
      to rats, AQP3, macrophages, cyclooxygenase 2 (COX2), and prostaglandin E(2)
      (PGE(2)) were examined in the colon. The mechanism by which bisacodyl decreases
      the expression of AQP3 was examined using HT-29 and Raw264.7 cells. When diarrhea
      occurred, a significant increase in the expression of PGE(2) and a decrease in
      AQP3 expression were observed. Immunostaining showed COX2 expression only in
      macrophages. The PGE(2) concentration increased significantly 30 min after the
      addition of bisacodyl to Raw264.7 cells. Thirty minutes after PGE(2) addition to
      HT-29 cells, the AQP3 expression level decreased to 40% of the control. When
      pretreated with indomethacin, bisacodyl did not induce an increase in the colon
      PGE(2) level, a decrease in the AQP3 expression level, or diarrhea. The results
      suggest that bisacodyl may decrease the expression of AQP3 in the colon, which
      inhibits water transfer from the luminal to the vascular side and leads to a
      laxative effect. This study also showed that direct activation of colon
      macrophages by bisacodyl increases the secretion of PGE(2), which acts as a
      paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells.

PMID- 21868636
TI  - Induction of Sca-1 via activation of STAT3 system in the duct cells of the mouse
      submandibular gland by ligation of the main excretory duct.
AB  - To examine the very initial step that takes place immediately after tissue injury
      and is linked to tissue regeneration, we employed the submandibular gland (SMG),
      which was injured by ligation of its main excretory duct (MED). Ligation of the
      MED of the SMG in mice induced the expression of Sca-1, a protein marker of
      hematopoietic stem cells. In the normal gland, a low level of Sca-1 was
      expressed, which was localized predominantly in the excretory duct cells. At 1
      day after ligation, Sca-1 expression increased prominently in almost all of cells
      in the duct system, but not in the acinar cells. The level of Sca-1 mRNA had
      begun to increase at 6 h after ligation and continuously rose thereafter until it
      reached a plateau, which occurred ~12 h after ligation. STAT3 phosphorylated at
      its tyrosine-705 (p-STAT3) in the ligated gland increased immediately after
      ligation, and it was localized in the nuclei of all duct cells. The results of an
      EMSA revealed the specific binding of a nuclear extract to the sequence of the
      gamma-interferon activation site (GAS) present in the Sca-1 promoter and
      confirmed that such binding increased after ligation. Thus the present study
      suggests that STAT3, having been phosphorylated following MED ligation, was
      transferred to the nucleus, where it bound to the GAS element in the promoter of
      Sca-1 gene, resulting in promotion of Sca-1 gene expression. Actual prevention of
      STAT3 phosphorylation reduced the ligation-induced Sca-1 elevation.

PMID- 21868637
TI  - Much more than a telescope.

PMID- 21868642
TI  - Scientific ocean drilling. U.S. to leave consortium and go it alone after 2013.

PMID- 21868643
TI  - Newsmaker interview: Leszek Borysiewicz. Cambridge seeks global reach, says
      university head. Interview by Colin Macilwain.

PMID- 21868644
TI  - Planetary science. Hayabusa gets to the bottom of deceptive asteroid cloaking.

PMID- 21868645
TI  - Biodiversity. 8.7 million: a new estimate for all the complex species on Earth.

PMID- 21868646
TI  - Paleoanthropology. Who were the Denisovans?

PMID- 21868647
TI  - Paleoanthropology. A Denisovan legacy in the immune system?

PMID- 21868648
TI  - Tissue engineering. Mending the youngest hearts.

PMID- 21868650
TI  - European universities. Can these networks KIC-start European innovation?

PMID- 21868649
TI  - European universities. Europe's innovation engine, eager to grow, faces
      criticism.

PMID- 21868651
TI  - Predators' effects on ecosystem entropy.

PMID- 21868652
TI  - Endangered wolves fall prey to politics.

PMID- 21868654
TI  - Comment on "Drought-induced reduction in global terrestrial net primary
      production from 2000 through 2009".
AB  - Zhao and Running (Reports, 20 August 2010, p. 940) reported that global net
      primary production has declined over the past decade and that this reduction was
      caused by drought. However, their findings are not direct measurements, but
      rather are based on outcomes from models in which a strong temperature dependence
      is assumed. I examine the assumptions underlying their results and show that
      their findings can be explained as logical consequences of these assumptions.

PMID- 21868655
TI  - Comment on "Drought-induced reduction in global terrestrial net primary
      production from 2000 through 2009".
AB  - Zhao and Running (Reports, 20 August 2010, p. 940) reported a reduction in global
      terrestrial net primary production (NPP) from 2000 through 2009. We argue that
      the small trends, regional patterns, and interannual variations that they
      describe are artifacts of their NPP model. Satellite observations of vegetation
      activity show no statistically significant changes in more than 85% of the
      vegetated lands south of 70 degrees N during the same 2000 to 2009 period.

PMID- 21868657
TI  - Looking to NSF as an NIH model.

PMID- 21868658
TI  - Science education. Drawing to learn in science.

PMID- 21868659
TI  - Planetary science. Bringing part of an asteroid back home.

PMID- 21868660
TI  - Cell biology. Arranging a cellular checkerboard.

PMID- 21868661
TI  - Evolution. How great wings can look alike.

PMID- 21868662
TI  - Cancer. Another NOTCH for cancer.

PMID- 21868663
TI  - Plant science. A window on the sophistication of plants.

PMID- 21868664
TI  - Chemistry. Architecturally complex polymers with controlled heterogeneity.

PMID- 21868665
TI  - SPORE series winner. Astronomical perspectives for young children.

PMID- 21868666
TI  - Mitochondria and the autophagy-inflammation-cell death axis in organismal aging.
AB  - Alterations of mitochondrial functions are linked to multiple degenerative or
      acute diseases. As mitochondria age in our cells, they become progressively
      inefficient and potentially toxic, and acute damage can trigger the
      permeabilization of mitochondrial membranes to initiate apoptosis or necrosis.
      Moreover, mitochondria have an important role in pro-inflammatory signaling.
      Autophagic turnover of cellular constituents, be it general or specific for
      mitochondria (mitophagy), eliminates dysfunctional or damaged mitochondria, thus
      counteracting degeneration, dampening inflammation, and preventing unwarranted
      cell loss. Decreased expression of genes that regulate autophagy or mitophagy can
      cause degenerative diseases in which deficient quality control results in
      inflammation and the death of cell populations. Thus, a combination of
      mitochondrial dysfunction and insufficient autophagy may contribute to multiple
      aging-associated pathologies.

PMID- 21868667
TI  - Itokawa dust particles: a direct link between S-type asteroids and ordinary
      chondrites.
AB  - The Hayabusa spacecraft successfully recovered dust particles from the surface of
      near-Earth asteroid 25143 Itokawa. Synchrotron-radiation x-ray diffraction and
      transmission and scanning electron microscope analyses indicate that the
      mineralogy and mineral chemistry of the Itokawa dust particles are identical to
      those of thermally metamorphosed LL chondrites, consistent with spectroscopic
      observations made from Earth and by the Hayabusa spacecraft. Our results directly
      demonstrate that ordinary chondrites, the most abundant meteorites found on
      Earth, come from S-type asteroids. Mineral chemistry indicates that the majority
      of regolith surface particles suffered long-term thermal annealing and subsequent
      impact shock, suggesting that Itokawa is an asteroid made of reassembled pieces
      of the interior portions of a once larger asteroid.

PMID- 21868668
TI  - Oxygen isotopic compositions of asteroidal materials returned from Itokawa by the
      Hayabusa mission.
AB  - Meteorite studies suggest that each solar system object has a unique oxygen
      isotopic composition. Chondrites, the most primitive of meteorites, have been
      believed to be derived from asteroids, but oxygen isotopic compositions of
      asteroids themselves have not been established. We measured, using secondary ion
      mass spectrometry, oxygen isotopic compositions of rock particles from asteroid
      25143 Itokawa returned by the Hayabusa spacecraft. Compositions of the particles
      are depleted in (16)O relative to terrestrial materials and indicate that
      Itokawa, an S-type asteroid, is one of the sources of the LL or L group of
      equilibrated ordinary chondrites. This is a direct oxygen-isotope link between
      chondrites and their parent asteroid.

PMID- 21868669
TI  - Neutron activation analysis of a particle returned from asteroid Itokawa.
AB  - A single grain (~3 micrograms) returned by the Hayabusa spacecraft was analyzed
      by neutron activation analysis. This grain is mainly composed of olivine with
      minor amounts of plagioclase, troilite, and metal. Our results establish that the
      Itokawa sample has similar chemical characteristics (iron/scandium and
      nickel/cobalt ratios) to chondrites, confirming that this grain is
      extraterrestrial in origin and has primitive chemical compositions. Estimated
      iridium/nickel and iridium/cobalt ratios for metal in the Itokawa samples are
      about five times lower than CI carbonaceous chondrite values. A similar depletion
      of iridium was observed in chondrule metals of ordinary chondrites. These metals
      must have condensed from the nebular where refractory siderophile elements
      already condensed and were segregated.

PMID- 21868670
TI  - Incipient space weathering observed on the surface of Itokawa dust particles.
AB  - The reflectance spectra of the most abundant meteorites, ordinary chondrites, are
      different from those of the abundant S-type (mnemonic for siliceous) asteroids.
      This discrepancy has been thought to be due to space weathering, which is an
      alteration of the surfaces of airless bodies exposed to the space environment.
      Here we report evidence of space weathering on particles returned from the S-type
      asteroid 25143 Itokawa by the Hayabusa spacecraft. Surface modification was found
      in 5 out of 10 particles, which varies depending on mineral species. Sulfur
      bearing Fe-rich nanoparticles exist in a thin (5 to 15 nanometers) surface layer
      on olivine, low-Ca pyroxene, and plagioclase, which is suggestive of vapor
      deposition. Sulfur-free Fe-rich nanoparticles exist deeper inside (<60
      nanometers) ferromagnesian silicates. Their texture suggests formation by
      metamictization and in situ reduction of Fe(2+).

PMID- 21868671
TI  - Three-dimensional structure of Hayabusa samples: origin and evolution of Itokawa
      regolith.
AB  - Regolith particles on the asteroid Itokawa were recovered by the Hayabusa
      mission. Their three-dimensional (3D) structure and other properties, revealed by
      x-ray microtomography, provide information on regolith formation. Modal
      abundances of minerals, bulk density (3.4 grams per cubic centimeter), and the 3D
      textures indicate that the particles represent a mixture of equilibrated and less
      equilibrated LL chondrite materials. Evidence for melting was not seen on any of
      the particles. Some particles have rounded edges. Overall, the particles' size
      and shape are different from those seen in particles from the lunar regolith.
      These features suggest that meteoroid impacts on the asteroid surface primarily
      form much of the regolith particle, and that seismic-induced grain motion in the
      smooth terrain abrades them over time.

PMID- 21868672
TI  - Irradiation history of Itokawa regolith material deduced from noble gases in the
      Hayabusa samples.
AB  - Noble gas isotopes were measured in three rocky grains from asteroid Itokawa to
      elucidate a history of irradiation from cosmic rays and solar wind on its
      surface. Large amounts of solar helium (He), neon (Ne), and argon (Ar) trapped in
      various depths in the grains were observed, which can be explained by multiple
      implantations of solar wind particles into the grains, combined with preferential
      He loss caused by frictional wear of space-weathered rims on the grains. Short
      residence time of less than 8 million years was implied for the grains by an
      estimate on cosmic-ray-produced (21)Ne. Our results suggest that Itokawa is
      continuously losing its surface materials into space at a rate of tens of
      centimeters per million years. The lifetime of Itokawa should be much shorter
      than the age of our solar system.

PMID- 21868673
TI  - Synthesis and structure determination of the hierarchical meso-microporous
      zeolite ITQ-43.
AB  - The formation of mesopores in microporous zeolites is generally performed by
      postsynthesis acid, basic, and steam treatments. The hierarchical pore systems
      thus formed allow better adsorption, diffusion, and reactivity of these
      materials. By combining organic and inorganic structure-directing agents and high
      throughput methodologies, we were able to synthesize a zeolite with a
      hierarchical system of micropores and mesopores, with channel openings delimited
      by 28 tetrahedral atoms. Its complex crystalline structure was solved with the
      use of automated diffraction tomography.

PMID- 21868674
TI  - Unraveling the perplexing structure of the zeolite SSZ-57.
AB  - Previous high-resolution x-ray powder diffraction and transmission electron
      microscopy studies of the zeolite SSZ-57 could not fully elucidate the structural
      basis for its puzzling adsorption behavior, which appears to be intermediate
      between that of a medium- (10-ring) and a large-pore (12-ring) zeolite. Now by
      applying advanced crystallographic techniques (structure solution in four
      dimensional space and interpretation of three-dimensional diffuse scattering by
      Monte Carlo simulation) and crystal chemistry considerations to high-quality
      single-crystal x-ray diffraction data collected on a microcrystal (about 2
      micrometers by 2 micrometers by 8 micrometers), we have been able to derive a
      comprehensive description of its silicate framework structure. The framework is
      related to that of ZSM-11 but is commensurately modulated along the c axis (P4m2,
      a = b = 20.091 A, c = 110.056 A) to yield a structure with a 12-ring:10-ring
      ratio of 1:15. Disorder of the 12-rings results in a three-dimensional 10-ring
      channel system with large isolated pockets. The structure helps to clarify the
      material's catalytic activity.

PMID- 21868675
TI  - Chaperonins facilitate KNOTTED1 cell-to-cell trafficking and stem cell function.
AB  - Cell-to-cell communication in plants includes the selective trafficking of
      transcription factors and other signals through plasmodesmata. The KNOTTED1 (KN1)
      homeobox (KNOX) family transcription factors, which use this pathway, are
      essential for stem cell establishment and/or maintenance. Here we show that KN1
      trafficking requires the chaperonin complex, which belongs to a group of
      cytosolic chaperones that fold specific substrate proteins. Genetic and physical
      interaction data show a functional relevance for chaperonins in KNOX family
      dependent stem cell maintenance. Furthermore, tissue-specific complementation
      assays indicate a mechanistic basis for chaperonin function during the
      posttranslocational refolding process. Our study shows that chaperonins are
      essential for the cell-to-cell trafficking of a subset of mobile transcription
      factors and demonstrates the importance of chaperonin-dependent protein
      trafficking for plant stem cell function.

PMID- 21868676
TI  - Expanding the genetic code of Escherichia coli with phosphoserine.
AB  - O-Phosphoserine (Sep), the most abundant phosphoamino acid in the eukaryotic
      phosphoproteome, is not encoded in the genetic code, but synthesized
      posttranslationally. Here, we present an engineered system for specific
      cotranslational Sep incorporation (directed by UAG) into any desired position in
      a protein by an Escherichia coli strain that harbors a Sep-accepting transfer RNA
      (tRNA(Sep)), its cognate Sep-tRNA synthetase (SepRS), and an engineered EF-Tu (EF
      Sep). Expanding the genetic code rested on reengineering EF-Tu to relax its
      quality-control function and permit Sep-tRNA(Sep) binding. To test our system, we
      synthesized the activated form of human mitogen-activated ERK activating kinase 1
      (MEK1) with either one or two Sep residues cotranslationally inserted in their
      canonical positions (Sep(218), Sep(222)). This system has general utility in
      protein engineering, molecular biology, and disease research.

PMID- 21868677
TI  - MED23 mutation links intellectual disability to dysregulation of immediate early
      gene expression.
AB  - MED23 is a subunit of the Mediator complex, a key regulator of protein-coding
      gene expression. Here, we report a missense mutation (p. R617Q) in MED23 that
      cosegregates with nonsyndromic autosomal recessive intellectual disability. This
      mutation specifically impaired the response of JUN and FOS immediate early genes
      (IEGs) to serum mitogens by altering the interaction between enhancer-bound
      transcription factors (TCF4 and ELK1, respectively) and Mediator. Transcriptional
      dysregulation of these genes was also observed in cells derived from patients
      presenting with other neurological disorders linked to mutations in other
      Mediator subunits or proteins interacting with MED. These findings highlight the
      crucial role of Mediator in brain development and functioning and suggest that
      altered IEG expression might be a common molecular hallmark of cognitive deficit.

PMID- 21868678
TI  - The "other" respiratory effect of opioids: suppression of spontaneous augmented
      ("sigh") breaths.
AB  - The purpose of this study was to examine the effects of a clinically relevant
      opioid on the production of augmented breaths (ABs) in unanesthetized animals
      breathing normal room air, using a dosage which does not depress breathing. To do
      this we monitored breathing noninvasively, in unrestrained animals before and
      after subcutaneous injection of either morphine, or a saline control. The effect
      of ketamine/xylazine was also studied to determine the potential effect of an
      alternative sedative agent. Last, the effect of naloxone was studied to determine
      the potential influence of endogenous opioids in regulating the normal incidence
      of ABs. Morphine (5 mg/kg) had no depressive effect on breathing, but completely
      eliminated ABs in all animals in room air (P = 0.027). However, when animals
      breathed hypoxic air (10% O(2)), animals did express ABs, although their
      incidence was still reduced by morphine (P < 0.001). This was not a result of
      sedation per se, as ABs continued at their normal rate in room air during
      sedation with ketamine. Naloxone had no effect on breathing or AB production, and
      so endogenous opioids are not likely involved in regulating their rate of
      production under normal conditions. Our results show that in unanesthetized
      animals breathing normal room air, a clinically relevant opioid eliminates ABs,
      even at a dose that does not cause respiratory depression. Despite this, hypoxia
      induced stimulation of breathing can facilitate the production of ABs even with
      the systemic opioid present, indicating that peripheral chemoreceptor stimulation
      provides a potential means of overcoming the opioid-induced suppression of these
      respiratory events.

PMID- 21868680
TI  - New images, new insights for VILI.

PMID- 21868679
TI  - Low-volume high-intensity interval training reduces hyperglycemia and increases
      muscle mitochondrial capacity in patients with type 2 diabetes.
AB  - Low-volume high-intensity interval training (HIT) is emerging as a time-efficient
      exercise strategy for improving health and fitness. This form of exercise has not
      been tested in type 2 diabetes and thus we examined the effects of low-volume HIT
      on glucose regulation and skeletal muscle metabolic capacity in patients with
      type 2 diabetes. Eight patients with type 2 diabetes (63 +/- 8 yr, body mass
      index 32 +/- 6 kg/m(2), Hb(A1C) 6.9 +/- 0.7%) volunteered to participate in this
      study. Participants performed six sessions of HIT (10 * 60-s cycling bouts
      eliciting ~90% maximal heart rate, interspersed with 60 s rest) over 2 wk. Before
      training and from ~48 to 72 h after the last training bout, glucose regulation
      was assessed using 24-h continuous glucose monitoring under standardized dietary
      conditions. Markers of skeletal muscle metabolic capacity were measured in biopsy
      samples (vastus lateralis) before and after (72 h) training. Average 24-h blood
      glucose concentration was reduced after training (7.6 +/- 1.0 vs. 6.6 +/- 0.7
      mmol/l) as was the sum of the 3-h postprandial areas under the glucose curve for
      breakfast, lunch, and dinner (both P < 0.05). Training increased muscle
      mitochondrial capacity as evidenced by higher citrate synthase maximal activity
      (~20%) and protein content of Complex II 70 kDa subunit (~37%), Complex III Core
      2 protein (~51%), and Complex IV subunit IV (~68%, all P < 0.05). Mitofusin 2
      (~71%) and GLUT4 (~369%) protein content were also higher after training (both P
      < 0.05). Our findings indicate that low-volume HIT can rapidly improve glucose
      control and induce adaptations in skeletal muscle that are linked to improved
      metabolic health in patients with type 2 diabetes.

PMID- 21868681
TI  - Improved VO2 uptake kinetics and shift in muscle fiber type in high-altitude
      trekkers.
AB  - The study investigated the effect of prolonged hypoxia on central [i.e.,
      cardiovascular oxygen delivery (Q(a)O(2))] and peripheral (i.e., O(2)
      utilization) determinants of oxidative metabolism response during exercise in
      humans. To this aim, seven male mountaineers were examined before and immediately
      after the Himalayan Expedition Interamnia 8000-Manaslu 2008, lasting 43 days,
      among which, 23 days were above 5,000 m. The subjects showed a decrease in body
      weight (P < 0.05) and of power output during a Wingate Anaerobic test (P < 0.05)
      and an increase of thigh cross-sectional area (P < 0.05). Absolute maximal O(2)
      uptake (VO(2max)) did not change. The mean response time of VO(2) kinetics at the
      onset of step submaximal cycling exercise was reduced significantly from 53.8 s
      +/- 10.9 to 39.8 s +/- 10.9 (P < 0.05), whereas that of Q(a)O(2) was not.
      Analysis of single fibers dissected from vastus lateralis biopsies revealed that
      the expression of slow isoforms of both heavy and light myosin subunits
      increased, whereas that of fast isoforms decreased. Unloaded shortening velocity
      of fibers was decreased significantly. In summary, independent findings converge
      in indicating that adaptation to chronic hypoxia brings about a fast-to-slow
      transition of muscle fibers, resulting in a faster activation of the
      mitochondrial oxidative metabolism. These results indicate that a prolonged and
      active sojourn in hypoxia may induce muscular ultrastructural and functional
      changes similar to those observed after aerobic training.

PMID- 21868682
TI  - Pharmacological curve fitting to analyze cutaneous adrenergic responses.
AB  - Although dose-response curves are commonly used to describe in vivo cutaneous
      alpha-adrenergic responses, modeling parameters and analyses methods are not
      consistent across studies. The goal of the present investigation was to compare
      three analysis methods for in vivo cutaneous vasoconstriction studies using one
      reference data set. Eight women (22 +/- 1 yr, 24 +/- 1 kg/m(2)) were instrumented
      with three cutaneous microdialysis probes for progressive norepinephrine (NE)
      infusions (1 * 10(-8), 1 * 10(-6), 1 * 10(-5), 1 * 10(-4), and 1 * 10(-3) logM).
      NE was infused alone, co-infused with NG-monomethyl-l-arginine (l-NMMA, 10 mM) or
      Ketorolac tromethamine (KETO, 10 mM). For each probe, dose-response curves were
      generated using three commonly reported analyses methods: 1) nonlinear modeling
      without data manipulation, 2) nonlinear modeling with data normalization and
      constraints, and 3) percent change from baseline without modeling. Not all data
      conformed to sigmoidal dose-response curves using analysis 1, whereas all
      subjects' curves were modeled using analysis 2. When analyzing only curves that
      fit the sigmoidal model, NE + KETO induced a leftward shift in ED(50) compared
      with NE alone with analyses 1 and 2 (F test, P < 0.05) but only tended to shift
      the response leftward with analysis 3 (repeated-measures ANOVA, P = 0.08).
      Neither maximal vasoconstrictor capacity (E(max)) in analysis 1 nor %change CVC
      change from baseline in analysis 3 were altered by blocking agents. In
      conclusion, although the overall detection of curve shifts and interpretation was
      similar between the two modeling methods of curve fitting, analysis 2 produced
      more sigmoidal curves.

PMID- 21868684
TI  - Extracting phase-dependent human vestibular reflexes during locomotion using both
      time and frequency correlation approaches.
AB  - Daily activities, such as walking, may require dynamic modulation of vestibular
      input onto motoneurons. This dynamic modulation is difficult to identify in
      humans due to limitations in the delivery and analysis of current vestibular
      probes, such as galvanic vestibular stimulation. Stochastic vestibular
      stimulation, however, provides an alternative method to extract human vestibular
      reflexes. Here, we used time-dependent coherence and time-dependent cross
      correlation, coupled with stochastic vestibular stimulation, to investigate the
      phase dependency of human vestibular reflexes during locomotion. We found that
      phase-dependent activity from the medial gastrocnemius muscles is correlated with
      the vestibular signals over the 2- to 20-Hz bandwidth during the stance phase of
      locomotion. Vestibular-gastrocnemius coherence and time-dependent cross
      correlations reached maximums at 21 +/- 4 and 23 +/- 8% of the step cycle
      following heel contact and before the period of maximal electromyographic
      activity (38 +/- 5%). These results demonstrate 1) the effectiveness of these
      techniques in extracting the phase-dependent modulation of vestibulomuscular
      coupling during a cyclic task; 2) that vestibulomuscular coupling is phasically
      modulated during locomotion; and 3) that the period of strongest
      vestibulomuscular coupling does not correspond to the period of maximal
      electromyographic activity in the gastrocnemius. Therefore, we have shown that
      stochastic vestibular stimulation, coupled with time-frequency decomposition,
      provides an effective tool to assess the contribution of vestibular ex-afference
      to the muscular control during locomotion.

PMID- 21868683
TI  - Effect of old age on human skeletal muscle force-velocity and fatigue properties.
AB  - It is generally accepted that the muscles of aged individuals contract with less
      force, have slower relaxation rates, and demonstrate a downward shift in their
      force-velocity relationship. The factors mediating age-related differences in
      skeletal muscle fatigue are less clear. The present study was designed to test
      the hypothesis that age-related shifts in the force-velocity relationship impact
      the fatigue response in a velocity-dependent manner. Three fatigue protocols,
      consisting of intermittent, maximum voluntary knee extension contractions
      performed for 4 min, were performed by 11 young (23.5 +/- 0.9 yr, mean +/- SE)
      and 10 older (68.9 +/- 4.3) women. The older group fatigued less during isometric
      contractions than the young group (to 71.1 +/- 3.7% initial torque and 59.8 +/-
      2.5%, respectively; P = 0.02), while the opposite was true during contractions
      performed at a relatively high angular velocity of 270 degrees .s(-1) (old: 28.0
      +/- 3.9% initial power, young: 52.1 +/- 6.9%; P < 0.01). Fatigue was not
      different (P = 0.74) between groups during contractions at an intermediate
      velocity, which was selected for each participant based on their force-velocity
      relationship. There was a significant association between force-velocity
      properties and fatigue induced by the intermediate-velocity fatigue protocol in
      the older (r = 0.72; P = 0.02) and young (r = 0.63; P = 0.04) groups. These
      results indicate that contractile velocity has a profound impact on age-related
      skeletal muscle fatigue resistance and suggest that changes in the force-velocity
      relationship partially mediate this effect.

PMID- 21868685
TI  - Sympathetic nerve activity and whole body heat stress in humans.
AB  - We and others have shown that moderate passive whole body heating (i.e.,
      increased internal temperature ~0.7 degrees C) increases muscle (MSNA) and skin
      sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA
      continue to increase with more severe passive whole body heating or whether these
      responses plateau following moderate heating. The aim of this investigation was
      to test the hypothesis that MSNA and SSNA continue to increase from a moderate to
      a more severe heat stress. Thirteen subjects, dressed in a water-perfused suit,
      underwent at least one passive heat stress that increased internal temperature
      ~1.3 degrees C, while either MSNA (n = 8) or SSNA (n = 8) was continuously
      recorded. Heat stress significantly increased mean skin temperature (Delta~5
      degrees C, P < 0.001), internal temperature (Delta~1.3 degrees C, P < 0.001),
      mean body temperature (Delta~2.0 degrees C, P < 0.001), heart rate (Delta~40
      beats/min, P < 0.001), and cutaneous vascular conductance [Delta~1.1 arbitrary
      units (AU)/mmHg, P < 0.001]. Mean arterial blood pressure was well maintained (P
      = 0.52). Relative to baseline, MSNA increased midway through heat stress (Delta
      core temperature 0.63 +/- 0.01 degrees C) when expressed as burst frequency (26
      +/- 14 to 45 +/- 16 bursts/min, P = 0.001), burst incidence (39 +/- 13 to 48 +/-
      14 bursts/100 cardiac cyles, P = 0.03), or total activity (317 +/- 170 to 489 +/-
      150 units/min, P = 0.02) and continued to increase until the end of heat stress
      (burst frequency: 61 +/- 15 bursts/min, P = 0.01; burst incidence: 56 +/- 11
      bursts/100 cardiac cyles, P = 0.04; total activity: 648 +/- 158 units/min, P =
      0.01) relative to the mid-heating stage. Similarly, SSNA (total activity)
      increased midway through the heat stress (normothermia; 1,486 +/- 472 to mid heat
      stress 6,467 +/- 5,256 units/min, P = 0.03) and continued to increase until the
      end of heat stress (11,217 +/- 6,684 units/min, P = 0.002 vs. mid-heat stress).
      These results indicate that both MSNA and SSNA continue to increase as internal
      temperature is elevated above previously reported values.

PMID- 21868686
TI  - The importance of biomechanical feedback in the generation of asthma.

PMID- 21868687
TI  - Acute response of plasma markers of bone turnover to a single bout of resistance
      training or plyometrics.
AB  - The time course of changes in plasma bone turnover markers following an acute
      bout of resistance training (RT) or plyometrics (PLY) has not been well
      characterized. This study is the first to compare the acute response of bone
      formation and resorption markers to a single bout of RT or PLY. Using a partially
      randomized, cross-over study design, 12 recreationally active men, aged 43 +/- 5
      yr, each completed four exercise trials: RT (Fed/Fasted) and PLY (Fed/Fasted). In
      addition to the RT and PLY trials, 5 of the original 12 participants also
      completed a fasted, no-exercise control trial to examine time-of-day variation.
      For each trial, blood was drawn immediately before exercise (PRE), immediately
      following exercise, and 15 min, 30 min, 1 h, 2 h, and 24 h following PRE for
      determination of plasma bone-specific alkaline phosphatase (BAP), osteocalcin
      (OC), tartrate-resistant acid phosphatase 5b (TRAP5b), COOH-terminal telopeptide
      of type I collagen (CTX), testosterone, parathyroid hormone, and cortisol. A one
      factor repeated-measures ANOVA was performed for each trial to detect changes in
      bone markers during the 2 h following RT or PLY. TRAP5b transiently decreased
      during the 2 h following all exercise trials (main effect for time, P < 0.05),
      but returned to PRE concentrations 2 h postexercise. BAP, CTX, and OC remained
      unchanged, except for reductions in BAP and CTX following PLY-Fasted and PLY-Fed,
      respectively. During the control trial, BAP decreased, while TRAP5b, CTX, and OC
      remained unchanged. In general, plasma hormone concentrations decreased during
      the 2 h following PLY or RT, and cumulative decreases in TRAP5b during the 2 h
      following exercise were positively correlated with cumulative decreases in
      parathyroid hormone. The results of the present study suggest that the timing of
      the measurement of bone turnover markers relative to the last exercise bout is
      important for detection of exercise-associated changes in bone turnover markers,
      as the markers returned to preexercise values within 2 h of RT or PLY.

PMID- 21868688
TI  - Medial patellofemoral ligament reconstruction with a divergent patellar
      transverse 2-tunnel technique.
AB  - BACKGROUND: The medial patellofemoral ligament (MPFL) is the primary passive
      restraint to lateral patellar dislocation and there is increasing awareness of
      its role in recurrent lateral patellar instability. PURPOSE: This study was
      conducted to prospectively analyze the functional results of a modified MPFL
      reconstruction technique in recurrent patellar dislocation. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Forty-eight patients (51 knees) with at
      least 3 episodes of lateral patellar dislocation who had been treated with a 6
      month rehabilitation protocol were included in this study. All patients practiced
      sports regularly. Reconstruction was with a semitendinosus tendon using a
      divergent 2-tunnel technique. Outcome was evaluated with the Kujala, Larsen,
      modified Lysholm, and Fulkerson outcome scores. Patient satisfaction with range
      of motion, pain, and sporting activities was also assessed. RESULTS: Three
      patients were lost at the final follow-up, giving a follow-up rate of 94%. The
      mean follow-up was 33 months. There was no patella dislocation postoperatively.
      The mean Kujala score improved significantly (P < .01) from 56.7 +/- 17.7 (2 *
      standard deviation) preoperatively to 86.8 +/- 14.4 postoperatively. The mean
      Larsen score improved significantly (P < .01) from 12.4 +/- 3.2 to 17.1 +/- 2.7.
      The mean Fulkerson score improved significantly (P < .01) from 59.2 +/- 21.8 to
      90.1 +/- 14. The mean modified Lysholm score improved significantly (P < .01)
      from 57.6 +/- 19.6 to 88.1 +/- 16.2. Sixty-four percent of patients returned to
      the same type of sport at the same level, 16% reduced the level or type of sport
      for reasons unrelated to the surgery, while 20% reduced the level of sport or
      changed it for reasons related to surgery. Eighty-seven percent were either
      satisfied or very satisfied with the pain relief achieved. The patellar tilt
      decreased significantly from a preoperative mean of 11.1 degrees  to 8.9 degrees 
      at the last follow-up (P = .02). The mean preoperative Insall-Salvati ratio of
      1.1 decreased to 1.06, although the change was not significant (P = .1).
      CONCLUSION: The results of modified MPFL reconstructions are encouraging, with
      minimal risks of redislocation and an overall patient satisfaction rate of over
      80%. These early and medium-term results are comparable with those of other MPFL
      reconstruction techniques reported in the literature.

PMID- 21868689
TI  - Osteochondral autograft transplantation for advanced stage Freiberg disease in
      adolescent athletes: a report of 3 cases and surgical procedures.

PMID- 21868690
TI  - Osteochondral transplantation in the elbow leads to good clinical and radiologic
      long-term results: an 8- to 14-year follow-up examination.
AB  - BACKGROUND: In the long-term follow-up after debridement, microfracture, or
      drilling of osteochondral lesions in the elbow, subsequent osteoarthritis is a
      problem. Osteochondral transplantation for these defects has become a more common
      procedure. However, long-term results are unknown. PURPOSE: This study was
      undertaken to evaluate long-term clinical and radiologic outcomes of advanced
      osteochondral lesions in the elbow treated with osteochondral transplantation.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study included 8
      patients with osteochondral lesions in the elbow who were treated by autologous
      osteochondral transplantation between 1996 and 2002. Patients (average age, 17
      years) were evaluated pre- and postoperatively by Broberg-Morrey score to assess
      elbow function and by American Shoulder and Elbow Surgeons (ASES) score for pain
      analysis. In addition, radiographs (at the first postoperative day, and at 5-year
      and 10-year follow-up) and magnetic resonance images (8 to 12 weeks
      postoperatively, and at 5-year and 10-year follow-up) were made to evaluate the
      joint status. At last follow-up (range, 8-14 years postoperatively), 7 of 8
      patients were seen for clinical examination and radiologic analysis. RESULTS: The
      Broberg-Morrey score increased from an average of 75.9 +/- 13.1 to 96.4 +/- 2.4
      and ASES score significantly improved as follows: worst pain, 7.9 +/- 1.1 to 1.6
      +/- 1.9; rest pain, 3.14 +/- 2.7 to 0.6 +/- 1.5; weight-lifting pain, 7.6 +/- 0.8
      to 3.1 +/- 1.6; and repetitive movement pain, 5.3 +/- 2.4 to 1.6 +/- 1.5.
      Compared with the contralateral side, there was a mean preoperative flexion lag
      of 12.5 degrees  +/- 11.6 degrees . At the final follow-up, flexion was free. The
      mean extension lag was reduced from average 5.4 degrees  +/- 5.7 degrees  to 0
      degrees . Radiographs of 2 patients made at final follow-up showed mild signs of
      osteoarthritis (Kellgren and Lawrence grade I). Postoperative magnetic resonance
      images showed graft viability in all and a congruent chondral surface in 6 of 7
      patients. CONCLUSION: Clinical long-term results after osteochondral
      transplantation in the elbow are good to excellent and comparable with midterm
      results in the literature. Therefore, this technique is a reliable option for
      satisfactory long-term results regarding treatment of advanced osteochondral
      lesions in the elbow.

PMID- 21868691
TI  - Autologous osteochondral transplantation of the talus partially restores contact
      mechanics of the ankle joint.
AB  - BACKGROUND: Autologous osteochondral transplantation procedures provide hyaline
      cartilage to the site of cartilage repair. It remains unknown whether these
      procedures restore native contact mechanics of the ankle joint. PURPOSE: This
      study was undertaken to characterize the regional and local contact mechanics
      after autologous osteochondral transplantation of the talus. STUDY DESIGN:
      Controlled laboratory study. METHODS: Ten fresh-frozen cadaveric lower limb
      specimens were used for this study. Specimens were loaded using a 6 degrees of
      freedom robotic arm with 4.5 N.m of inversion and a 300-N axial compressive load
      in a neutral plantar/dorsiflexion. An osteochondral defect was created at the
      centromedial aspect of the talar dome and an autologous osteochondral graft from
      the ipsilateral knee was subsequently transplanted to the defect site. Regional
      contact mechanics were analyzed across the talar dome as a function of the defect
      and repair conditions and compared with those in the intact ankle. Local contact
      mechanics at the peripheral rim of the defect and at the graft site were also
      analyzed and compared with the intact condition. A 3-dimensional laser scanning
      system was used to determine the graft height differences relative to the native
      talus. RESULTS: The creation of an osteochondral defect caused a significant
      decrease in force, mean pressure, and peak pressure on the medial region of the
      talus (P = .037). Implanting an osteochondral graft restored the force, mean
      pressure, and peak pressure on the medial region of the talus to intact levels (P
      = .05). The anterior portion of the graft carried less force, while mean and peak
      pressures were decreased relative to intact (P = .05). The mean difference in
      graft height relative to the surrounding host cartilage for the overall
      population was -0.2 +/- 0.3 mm (range, -1.00 to 0.40 mm). Under these conditions,
      there was no correlation between height and pressure when the graft was sunken,
      flush, or proud. CONCLUSION/CLINICAL RELEVANCE: Placement of the osteochondral
      graft in the most congruent position possible partially restored contact
      mechanics of the ankle joint. Persistent deficits in contact mechanics may be due
      to additional factors besides graft congruence, including structural differences
      in the donor cartilage when compared with the native tissue.

PMID- 21868692
TI  - Hepatocellular carcinoma in HIV-infected patients: check early, treat hard.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in
      HIV-infected patients in the highly active antiretroviral therapy (HAART) era.
      The aims of this study were to describe HCC tumor characteristics and different
      therapeutic approaches, to evaluate patient survival time from HCC diagnosis, and
      to identify clinical prognostic predictors in patients with and without HIV
      infection. PATIENTS AND METHODS: A multicenter observational retrospective
      comparison of 104 HIV-infected patients and 484 uninfected patients was performed
      in four Italian centers. HCC was staged according to the Barcelona Clinic Liver
      Cancer (BCLC) criteria. RESULTS: Tumor characteristics of patients with and
      without HIV were significantly different for age, Eastern Cooperative Oncology
      Group performance status (PS) score <=1, and etiology of chronic liver disease.
      Despite the similar potentially curative option rate and better BCLC stage at
      diagnosis, the median survival time was significantly shorter in HIV(+) patients.
      HIV(+) patients were less frequently retreated at relapse. Independent predictors
      of survival were: BCLC stage, potentially effective HCC therapy, tumor dimension
      <=3 cm, HCC diagnosis under a screening program, HCC recurrence, and portal vein
      thrombosis. Restricting the analysis to HIV(+) patients only, all positive
      prognostic factors were confirmed together with HAART exposure. CONCLUSION: This
      study confirms a significantly shorter survival time in HIV(+) HCC patients. The
      less aggressive retreatment at recurrence approach does not balance the benefit
      of younger age and better BCLC stage and PS score of HIV(+) patients. Thus,
      considering the prognosis of HIV(+) HCC patients, effective screening techniques,
      programs, and specific management guidelines are urgently needed.

PMID- 21868693
TI  - Microbiota of severe early childhood caries before and after therapy.
AB  - Severe early childhood caries (ECC) is difficult to treat successfully. This
      study aimed to characterize the microbiota of severe ECC and evaluate whether
      baseline or follow-up microbiotas are associated with new lesions post-treatment.
      Plaque samples from 2- to 6-year-old children were analyzed by a 16S rRNA-based
      microarray and by PCR for selected taxa. Severe-ECC children were monitored for
      12 months post-therapy. By microarray, species associated with severe-ECC (n =
      53) compared with caries-free (n = 32) children included Slackia exigua (p =
      0.002), Streptococcus parasanguinis (p = 0.013), and Prevotella species (p <
      0.02). By PCR, severe-ECC-associated taxa included Bifidobacteriaceae (p <
      0.001), Scardovia wiggsiae (p = 0.003), Streptococcus mutans with bifidobacteria
      (p < 0.001), and S. mutans with S. wiggsiae (p = 0.001). In follow-up, children
      without new lesions (n = 36) showed lower detection of taxa including S. mutans,
      changes not observed in children with follow-up lesions (n = 17). Partial least
      squares modeling separated the children into caries-free and two severe-ECC
      groups with either a stronger bacterial or a stronger dietary component. We
      conclude that several species, including S. wiggsiae and S. exigua, are
      associated with the ecology of advanced caries, that successful treatment is
      accompanied by a change in the microbiota, and that severe ECC is diverse, with
      influences from selected bacteria or from diet.

PMID- 21868694
TI  - B1a B lymphocytes are atheroprotective by secreting natural IgM that increases
      IgM deposits and reduces necrotic cores in atherosclerotic lesions.
AB  - RATIONALE: Aggravated atherosclerosis in B lymphocyte-deficient chimeric mice and
      reduced atherosclerosis after transfer of unfractionated spleen B lymphocytes
      into splenectomized mice have led to the widely held notion that B lymphocytes
      are atheroprotective. However, B lymphocytes can be pathogenic, because their
      depletion by anti-CD20 antibody ameliorated atherosclerosis, and transfer of B2
      lymphocytes aggravated atherosclerosis. These observations raise the question of
      the identity of the atheroprotective B-lymphocyte population. OBJECTIVE: The
      purpose of the study was to identify an atheroprotective B-lymphocyte subset and
      mechanisms by which they confer atheroprotection. METHODS AND RESULTS:
      Splenectomy of apolipoprotein E-deficient mice selectively reduced peritoneal B1a
      lymphocytes, plasma IgM, and oxidized low-density lipoprotein IgM levels and
      lesion IgM deposits. These reductions were accompanied by increased oil red O
      stained atherosclerotic lesions and increased necrotic cores, oxidized low
      density lipoproteins, and apoptotic cells in lesions. Plasma lipids, body weight,
      collagen, and smooth muscle content were unaffected. Transfer of B1a lymphocytes
      into splenectomized mice increased peritoneal B1a lymphocytes; restored plasma
      IgM, oxidized low-density lipoprotein IgM levels, and lesion IgM deposits; and
      potently attenuated atherosclerotic lesions, with reduced lesion necrotic cores,
      oxidized low-density lipoprotein, and apoptotic cells. In contrast, transfer of
      B1a lymphocytes that cannot secrete IgM failed to protect against atherosclerosis
      development in splenectomized mice despite reconstitution in the peritoneum.
      CONCLUSIONS: B1a lymphocytes are an atheroprotective B-lymphocyte population. Our
      data suggest that natural IgM secreted by these lymphocytes offers protection by
      depositing IgM in atherosclerotic lesions, which reduces the necrotic cores of
      lesions.

PMID- 21868695
TI  - Transplantation of human pericyte progenitor cells improves the repair of
      infarcted heart through activation of an angiogenic program involving micro-RNA
      132.
AB  - RATIONALE: Pericytes are key regulators of vascular maturation, but their value
      for cardiac repair remains unknown. OBJECTIVE: We investigated the therapeutic
      activity and mechanistic targets of saphenous vein-derived pericyte progenitor
      cells (SVPs) in a mouse myocardial infarction (MI) model. METHODS AND RESULTS:
      SVPs have a low immunogenic profile and are resistant to hypoxia/starvation
      (H/S). Transplantation of SVPs into the peri-infarct zone of immunodeficient
      CD1/Foxn-1(nu/nu) or immunocompetent CD1 mice attenuated left ventricular
      dilatation and improved ejection fraction compared to vehicle. Moreover, SVPs
      reduced myocardial scar, cardiomyocyte apoptosis and interstitial fibrosis,
      improved myocardial blood flow and neovascularization, and attenuated vascular
      permeability. SVPs secrete vascular endothelial growth factor A, angiopoietin-1,
      and chemokines and induce an endogenous angiocrine response by the host, through
      recruitment of vascular endothelial growth factor B expressing monocytes. The
      association of donor- and recipient-derived stimuli activates the proangiogenic
      and prosurvival Akt/eNOS/Bcl-2 signaling pathway. Moreover, microRNA-132 (miR
      132) was constitutively expressed and secreted by SVPs and remarkably
      upregulated, together with its transcriptional activator cyclic AMP response
      element-binding protein, on stimulation by H/S or vascular endothelial growth
      factor B. We next investigated if SVP-secreted miR-132 acts as a paracrine
      activator of cardiac healing. In vitro studies showed that SVP conditioned medium
      stimulates endothelial tube formation and reduces myofibroblast differentiation,
      through inhibition of Ras-GTPase activating protein and methyl-CpG-binding
      protein 2, which are validated miR-132 targets. Furthermore, miR-132 inhibition
      by antimiR-132 decreased SVP capacity to improve contractility, reparative
      angiogenesis, and interstitial fibrosis in infarcted hearts. CONCLUSION: SVP
      transplantation produces long-term improvement of cardiac function through a
      novel paracrine mechanism involving the secretion of miR-132 and inhibition of
      its target genes.

PMID- 21868696
TI  - Aptamer neutralization of beta1-adrenoceptor autoantibodies isolated from
      patients with cardiomyopathies.
AB  - RATIONALE: Autoantibodies directed against the beta1-adrenoceptor (beta1-AABs)
      have been proposed to drive the pathogenesis of idiopathic dilated
      cardiomyoparthy (DCM), Chagas' cardiomyopathy, and peripartum cardiomyopathy. For
      disease treatment, aptamers that bind and neutralize beta1-AABs could be
      significant. OBJECTIVE: We determined whether oligonucleotide-aptamers, selected
      to target human beta1-AABs directed against the second extracellular loop of the
      beta1-AAB, can neutralize these AABs and modulate their function in vitro.
      METHODS AND RESULTS: Using Monolex technology, we identified an ssDNA aptamer
      that targets human beta1-AABs. The neutralization potential of this aptamer
      against beta1-AABs isolated from patients with DCM, Chagas' cardiomyopathy, and
      peripartum cardiomyopathy was analyzed using cultured neonatal rat cardiomyocytes
      by monitoring beta1-AAB induced cell toxicity and chronotropic cell responses.
      Aptamer addition reduced beta1-AAB induced cell toxicity and neutralized
      chonotropic beta1-AAB function in a dose-dependent manner. In the presence of
      aptamer neutralized beta1-AABs, cells remained fully responsive to agonists and
      antagonists, such as isoprenaline and bisoprolol. Both aptamer pretreated with a
      complementary (antisense) aptamer and a control scrambled-sequence aptamer were
      ineffective at beta1-AAB neutralization. Beta1-AABs directed against the first
      extracellular loop of the beta1-receptor and AABs directed against other G
      protein coupled receptors were not affected by the selected aptamer. CONCLUSIONS:
      A specific aptamer that can neutralize cardiomyopathy associated human beta1-AABs
      in vitro has been identified and characterized, providing a framework for future
      in vivo testing of this treatment option in animal experiments.

PMID- 21868697
TI  - Regulatory T cells limit vascular endothelial injury and prevent pulmonary
      hypertension.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is an incurable disease
      associated with viral infections and connective tissue diseases. The relationship
      between inflammation and disease pathogenesis in these disorders remains poorly
      understood. OBJECTIVE: To determine whether immune dysregulation due to absent T
      cell populations directly contributes to the development of PAH. METHODS AND
      RESULTS: Vascular endothelial growth factor receptor 2 (VEGFR2) blockade induced
      significant pulmonary endothelial apoptosis in T-cell-deficient rats but not in
      immune-reconstituted (IR) rats. T cell-lymphopenia in association with VEGFR2
      blockade resulted in periarteriolar inflammation with macrophages, and B cells
      even prior to vascular remodeling and elevated pulmonary pressures. IR prevented
      early inflammation and attenuated PAH development. IR with either CD8 T cells
      alone or with CD4-depleted spleen cells was ineffective in preventing PAH,
      whereas CD4-depleting immunocompetent euthymic animals increased PAH
      susceptibility. IR with either CD4(+)CD25(hi) or CD4(+)CD25(-) T cell subsets
      prior to vascular injury attenuated the development of PAH. IR limited
      perivascular inflammation and endothelial apoptosis in rat lungs in association
      with increased FoxP3(+), IL-10- and TGF-beta-expressing CD4 cells, and
      upregulation of pulmonary bone morphogenetic protein receptor type 2 (BMPR2)
      expressing cells, a receptor that activates endothelial cell survival pathways.
      CONCLUSIONS: PAH may arise when regulatory T-cell (Treg) activity fails to
      control endothelial injury. These studies suggest that regulatory T cells
      normally function to limit vascular injury and may protect against the
      development of PAH.

PMID- 21868698
TI  - Urokinase-type plasminogen activator deficiency in bone marrow-derived cells
      augments rupture of angiotensin II-induced abdominal aortic aneurysms.
AB  - OBJECTIVE: Abdominal aortic aneurysms (AAAs) are associated with fragmentation of
      extracellular matrix during development of aortic dilation and rupture.
      Therefore, it is important to identify specific protease systems involved in
      extracellular matrix degradation during AAA formation. The present study
      determined the contribution of the urokinase system to AAA formation and rupture.
      METHODS AND RESULTS: Angiotensin II (Ang II)-induced AAAs were associated with
      increased aortic abundance of both urokinase-type plasminogen activator receptor
      (uPAR) and urokinase-type plasminogen activator (uPA) proteins. However, this
      increased presence was unrelated to AAA formation because deficiencies of either
      uPAR or uPA had no effect on either the incidence or size of Ang II-induced AAAs
      in both normolipidemic mice and low-density lipoprotein receptor-/- mice fed a
      saturated fat-enriched diet. Although uPA deficiency did not affect development
      of AAAs, there was an effect of increasing mortality rate from AAA rupture in
      hypercholesterolemic mice. Bone marrow transplantation demonstrated that enhanced
      aneurysmal rupture was attributable to deficiency of uPA in leukocytes. uPA
      deficiency led to an increased propensity for impaired resolution of the
      thrombotic material within the aneurysmal tissue. Neither uPAR nor uPA deficiency
      had any effect on Ang II-induced atherosclerosis in low-density lipoprotein
      receptor-/- mice. CONCLUSIONS: The uPA-uPAR axis has no effect on the formation
      of Ang II-induced AAAs, but uPA deficiency promotes aneurysmal rupture.

PMID- 21868699
TI  - Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage
      proliferation.
AB  - OBJECTIVE: Common genetic variants in a 58-kb region of chromosome 9p21, near the
      CDKN2A/CDKN2B tumor suppressor locus, are strongly associated with coronary
      artery disease. However, the underlying mechanism of action remains unknown.
      METHODS AND RESULTS: We previously reported a congenic mouse model harboring an
      atherosclerosis susceptibility locus and the region of homology with the human
      9p21 locus. Microarray and transcript-specific expression analyses showed
      markedly decreased Cdkn2a expression, including both p16(INK4a) and p19(ARF), but
      not Cdkn2b (p15(INK4b)), in macrophages derived from congenic mice compared with
      controls. Atherosclerosis studies in subcongenic strains revealed genetic
      complexity and narrowed 1 locus to a small interval including Cdkn2a/b. Bone
      marrow (BM) transplantation studies implicated myeloid lineage cells as the
      culprit cell type, rather than resident vascular cells. To directly test the role
      of BM-derived Cdkn2a transcripts in atherogenesis and inflammatory cell
      proliferation, we performed a transplantation study using Cdkn2a(-/-) cells in
      the Ldlr(-/-) mouse model. Cdkn2a-deficient BM recipients exhibited accelerated
      atherosclerosis, increased Ly6C proinflammatory monocytes, and increased
      monocyte/macrophage proliferation compared with controls. CONCLUSION: These data
      provide a plausible mechanism for accelerated atherogenesis in susceptible
      congenic mice, involving decreased expression of Cdkn2a and increased
      proliferation of monocyte/macrophages, with possible relevance to the 9p21 human
      locus.

PMID- 21868700
TI  - Smooth muscle cholesterol enables BK beta1 subunit-mediated channel inhibition
      and subsequent vasoconstriction evoked by alcohol.
AB  - OBJECTIVE: Hypercholesterolemia and alcohol drinking constitute independent risk
      factors for cerebrovascular disease. Alcohol constricts cerebral arteries in
      several species, including humans. This action results from inhibition of voltage
      and calcium-gated potassium channels (BK) in vascular smooth muscle cells
      (VSMC). BK activity is also modulated by membrane cholesterol. We investigated
      whether VSMC cholesterol regulates ethanol actions on BK and cerebral arteries.
      METHODS AND RESULTS: After myogenic tone development, cholesterol depletion of
      rat, resistance-size cerebral arteries ablated ethanol-induced constriction, a
      result that was identical in intact and endothelium-free vessels. Cholesterol
      depletion reduced ethanol inhibition of BK whether the channel was studied in
      VSMC or after rat cerebral artery myocyte subunit (cbv1+beta1) reconstitution
      into phospholipid bilayers. Homomeric cbv1 channels reconstituted into bilayers
      and VSMC BK from beta1 knockout mice were both resistant to ethanol-induced
      inhibition. Moreover, arteries from beta1 knockout mice failed to respond to
      ethanol even when VSMC cholesterol was kept unmodified. Remarkably, ethanol
      inhibition of cbv1+beta1 in bilayers and wt mouse VSMC BK were drastically
      blunted by cholesterol depletion. Consistently, cholesterol depletion suppressed
      ethanol constriction of wt mouse arteries. CONCLUSION: VSMC cholesterol and BK
      beta1 are both required for ethanol inhibition of BK and the resulting cerebral
      artery constriction, with health-related implications for manipulating
      cholesterol levels in alcohol-induced cerebrovascular disease.

PMID- 21868701
TI  - Slingshot isoform-specific regulation of cofilin-mediated vascular smooth muscle
      cell migration and neointima formation.
AB  - OBJECTIVE: We hypothesized that cofilin activation by members of the slingshot
      (SSH) phosphatase family is a key mechanism regulating vascular smooth muscle
      cell (VSMC) migration and neoinitima formation following vascular injury. METHODS
      AND RESULTS: Scratch wound and modified Boyden chamber assays were used to assess
      VSMC migration following downregulation of the expression of cofilin and each SSH
      phosphatase isoform (SSH1, SSH2, and SSH3) by small interfering RNA (siRNA),
      respectively. Cofilin siRNA greatly attenuated the ability of VSMC migration into
      the "wound," and platelet-derived growth factor (PDGF)-induced migration was
      virtually eliminated versus a 3.5-fold increase in nontreated VSMCs, establishing
      a critical role for cofilin in VSMC migration. Cofilin activation
      (dephosphorylation) was increased in PDGF-stimulated VSMCs. Thus, we assessed the
      role of the SSH family of phosphatases on cofilin activation and VSMC migration.
      Treatment with either SSH1 or SSH2 siRNA attenuated cofilin activation, whereas
      SSH3 siRNA had no effect. Only SSH1 siRNA significantly reduced wound healing and
      PDGF-induced VSMC migration. Both SSH1 expression (4.7-fold) and cofilin
      expression (3.9-fold) were increased in balloon injured versus noninjured carotid
      arteries, and expression was prevalent in the neointima. CONCLUSION: These
      studies demonstrate that the regulation of VSMC migration by cofilin is SSH1
      dependent and that this mechanism potentially contributes to neointima formation
      following vascular injury in vivo.

PMID- 21868702
TI  - Myofibroblast-mediated adventitial remodeling: an underestimated player in
      arterial pathology.
AB  - The arterial adventitia has been long considered an essentially supportive
      tissue; however, more and more data suggest that it plays a major role in the
      modulation of the vascular tone by complex interactions with structures located
      within intima and media. The purpose of this review is to summarize these data
      and to describe the mechanisms involved in adventitia/media and adventitia/intima
      cross-talk. In response to a plethora of stimuli, the adventitia undergoes
      remodeling processes, resulting in positive (adaptive) remodeling, negative
      (constrictive) remodeling, or both. The differentiation of the adventitial
      fibroblast into myofibroblast (MF), a key player of wound healing and fibrosis
      development, is a hallmark of negative remodeling; this can lead to vessel
      stenosis and thus contribute to major cardiovascular diseases. The mechanisms of
      fibroblast-to-MF differentiation and the role of the MF in adventitial remodeling
      are highlighted herein.

PMID- 21868703
TI  - Heme induces heme oxygenase 1 via Nrf2: role in the homeostatic macrophage
      response to intraplaque hemorrhage.
AB  - OBJECTIVE: Intraplaque hemorrhage (IPH) is an important progression event in
      advanced atherosclerosis, in large part because of the delivery of prooxidant
      hemoglobin in erythrocytes. We have previously defined a novel macrophage
      phenotype (hemorrhage-associated-mac) in human advanced plaques with IPH. These
      may be atheroprotective in view of raised heme oxygenase 1 (HO-1), CD163, and
      interleukin-10 expression and suppressed oxidative stress. METHODS AND RESULTS:
      We have used a combination of small interfering RNA and pharmacological reagents,
      protein analysis, and oxidative stress measurements to dissect the pathway
      leading to the development of this phenotype. We found that erythrocytes,
      hemoglobin, or purified heme similarly induced CD163 and suppressed human
      leukocyte antigen and reactive oxygen species. HO-1 was required for the
      development of each of these features. Challenge of macrophages with purified
      heme provoked nuclear translocation of Nrf2, and Nrf2 small interfering RNA
      resulted in significant inhibition of the ability of heme to induce HO-1 protein.
      Furthermore, tert-butyl-hydroquinone, which activates Nrf2, upregulated CD163,
      suppressed human leukocyte antigen, and induced interleukin-10, further
      supporting a role for Nrf2-mediated signaling. However, an inducible protein
      transactivator is also probably necessary, as heme-induced HO-1 mRNA expression
      was fully inhibited by the protein synthesis inhibitor cycloheximide. CONCLUSION:
      Our experiments define an Nrf2-mediated pathway by which heme induces a
      homeostatic macrophage response following IPH.

PMID- 21868704
TI  - Cathepsin L activity is essential to elastase perfusion-induced abdominal aortic
      aneurysms in mice.
AB  - OBJECTIVE: The development of abdominal aortic aneurysms (AAA) requires extensive
      aortic wall matrix degradation. Human AAA lesions express high levels of
      cathepsin L (CatL), one of the most potent mammalian elastases. Whether this
      protease participates directly in AAA pathogenesis, however, is unknown. METHODS
      AND RESULTS: We generated experimental AAA with aortic elastase perfusion in mice
      and established an essential role of CatL in AAA formation. After 14 days
      postperfusion, most wild-type (Ctsl(+/+)) mice developed AAA, but none of the
      CatL-deficient (Ctsl(-/-)) mice did. AAA lesion macrophage contents, CD4(+) T
      cell numbers, CD31(+) and laminin-5 angiogenic fragment gamma2(+) microvessel
      numbers, and elastin fragmentation were all significantly lower in Ctsl(-/-) mice
      than in Ctsl(+/+) mice. While lesions from Ctsl(-/-) mice contained fewer Ki67(+)
      proliferating cells than did Ctsl(+/+) mice, the absence of CatL did not affect
      lesion apoptotic cell contents or medial smooth-muscle cell loss significantly.
      Mechanistic studies indicated that the absence of CatL reduced lesion chemokine
      monocyte chemotactic protein-1 content, macrophage and T-cell in vitro
      transmigration, and angiogenesis, and altered the expression and activities of
      matrix metalloproteinases and other cysteinyl cathepsins in inflammatory cells,
      vascular cells, and AAA lesions. CONCLUSION: CatL contributes to AAA formation by
      promoting lesion inflammatory cell accumulation, angiogenesis, and protease
      expression.

PMID- 21868705
TI  - Calcification in major vessel beds relates to vascular brain disease.
AB  - OBJECTIVE: Calcification in atherosclerotic plaques is a novel marker of
      atherosclerosis and is related to cardiovascular disease. However, its
      relationship with cerebrovascular disease has not been investigated extensively.
      We investigated the relationship between calcification in various vessel beds
      outside the brain and imaging markers of vascular brain disease. METHODS AND
      RESULTS: A total of 885 community-dwelling people (mean age, 66.7 years)
      underwent computed tomography of the coronary arteries, aortic arch, and
      extracranial and intracranial carotid arteries to assess arterial calcification.
      Brain magnetic resonance imaging scans were performed to assess cerebral
      infarcts, microbleeds, and white matter lesions (WMLs). Calcification in each
      vessel bed was associated with presence of cerebral infarcts and with larger WML
      volume. The most prominent associations were found between intracranial carotid
      calcification and WML volume and between extracranial carotid calcification and
      infarcts. Adjustment for cardiovascular risk factors or ultrasound carotid plaque
      scores did not change these results. No associations were found between
      calcification and cerebral microbleeds. CONCLUSIONS: Arterial calcification in
      major vessel beds is associated with vascular brain disease on magnetic resonance
      imaging. Most notably, larger intracranial carotid calcification load relates to
      larger WML volumes, and larger extracranial carotid calcification load relates to
      the presence of cerebral infarcts, independently of ultrasound carotid plaque
      score. This suggests that calcification of atherosclerotic plaque yields other
      information in addition to merely the presence of plaques, providing novel
      insights into the etiology of vascular brain disease.

PMID- 21868706
TI  - Tissue factor regulates microvessel formation and stabilization by induction of
      chemokine (C-C motif) ligand 2 expression.
AB  - OBJECTIVE: Tissue factor (TF) triggers arterial thrombosis. TF is also able to
      initiate cellular signaling mechanisms leading to angiogenesis. Because high
      cardiovascular risk atherosclerotic plaques show significant angiogenesis, our
      objective was to investigate whether TF is able to trigger and stabilize
      atherosclerotic plaque neovessel formation. METHODS AND RESULTS: In this study,
      we showed, by real-time confocal microscopy in 3-dimensional basement membrane
      cocultures, that TF in human microvascular endothelial cells (HMEC-1) and in
      human vascular smooth muscle cells (HVSMCs) plays an important role in the
      formation of capillary-like networks. TF silencing in endothelial cells and
      smooth muscle cells inhibits the formation of tube-like structures with stable
      phenotype. Using an in vivo model, we observed that TF inhibition in either HMEC
      1 or HVSMCs reduced their shared ability to form new capillaries. The phenotypic
      changes induced by TF silencing were linked to reduced chemokine (C-C motif)
      ligand 2 (CCL2) expression in endothelial cells. Wound healing and chemotactic
      assays demonstrated that TF-induced release of CCL2 stimulated HVSMC migration to
      HMEC-1. CONCLUSION: Endogenous TF regulates CCL2 production in endothelial cells.
      Secreted CCL2 mediates the angiogenic effect of TF by recruiting smooth muscle
      cells toward endothelial cells and facilitates the maturation of newly formed
      microvessels.

PMID- 21868707
TI  - Potentiation of platelet-derived growth factor receptor-beta signaling mediated
      by integrin-associated MFG-E8.
AB  - OBJECTIVE: Pericytes/pericyte precursors produce milk fat globule-associated
      protein with epidermal growth factor and factor VIII-like domains (MFG-E8) in
      vivo, and this alpha(v) integrin ligand enhances angiogenesis in tumors and in
      oxygen-induced retinopathy in mice. Inhibition of MFG-E8 production or function
      attenuates platelet-derived growth factor-BB (PDGF-BB)-induced migration of
      pericyte/pericyte precursor-like 10T1/2 cells in vitro. Herein, we describe
      mechanisms by which MFG-E8 modulates PDGF-BB:PDGF receptor beta (PDGFRbeta)
      signaling in 10T1/2 cells. METHODS AND RESULTS: Small interfering RNA depletion
      of MFG-E8 from 10T1/2 cells or antibody inhibition of MFG-E8 action enhanced PDGF
      BB-dependent degradation of PDGFRbeta and attenuated signaling.
      Coimmunoprecipitation revealed transient association of MFG-E8 with PDGFRbeta in
      PDGF-BB-treated 10T1/2 cells and reduced PDGFRbeta-focal adhesion kinase
      association in MFG-E8-depleted cells. Confocal microscopy demonstrated that MFG
      E8 binding to 10T1/2 cells was RGD motif and alpha(v) dependent but PDGF-BB
      treatment independent, whereas colocalization of MFG-E8 with PDGFRbeta was
      enhanced by PDGF-BB. Ubiquitination of PDGFRbeta was also increased in MFG-E8
      small interfering RNA-transfected cells. CONCLUSION: Integrin alpha(v)-bound MFG
      E8 associates with PDGFRbeta and focal adhesion kinase after PDGF-BB treatment,
      results in cell surface retention of PDGFRbeta, delays receptor degradation,
      potentiates downstream signaling, and enhances migration of 10T1/2 cells. MFG-E8
      may promote angiogenesis, in part, via cell autonomous actions on pericytes or
      pericyte precursors that result in enhanced PDGF-BB:PDGFRbeta signaling mediated
      via integrin-growth factor receptor cross-talk.

PMID- 21868712
TI  - Tempol ameliorates pharyngeal dilator muscle dysfunction in a rodent model of
      chronic intermittent hypoxia.
AB  - Respiratory muscle dysfunction is implicated in the pathophysiology of
      obstructive sleep apnea syndrome (OSAS), an oxidative stress disorder prevalent
      in men. Pharmacotherapy for OSAS is an attractive option, and antioxidant
      treatments may prove beneficial. We examined the effects of chronic intermittent
      hypoxia (CIH) on breathing and pharyngeal dilator muscle structure and function
      in male and female rats. Additionally, we tested the efficacy of antioxidant
      treatment in preventing (chronic administration) or reversing (acute
      administration) CIH-induced effects in male rats. Adult male and female Wistar
      rats were exposed to alternating cycles of normoxia and hypoxia (90 s each;
      Fi(O(2)) = 5% O(2) at nadir; Sa(O(2)) ~ 80%) or sham treatment for 8 h/d for 9
      days. Tempol (1 mM, superoxide dismutase mimetic) was administered to subgroups
      of sham- and CIH-treated animals. Breathing was assessed by whole-body
      plethysmography. Sternohyoid muscle contractile and endurance properties were
      examined in vitro. Muscle fiber type and cross-sectional area and the activity of
      key metabolic enzymes were determined. CIH decreased sternohyoid muscle force in
      male rats only. This was not attributable to fiber transitions or alterations in
      oxidative or glycolytic enzyme activity. Muscle weakness after CIH was prevented
      by chronic Tempol supplementation and was reversed by acute antioxidant treatment
      in vitro. CIH increased normoxic ventilation in male rats only. Sex differences
      exist in the effects of CIH on the respiratory system, which may contribute to
      the higher prevalence of OSAS in male subjects. Antioxidant treatment may be
      beneficial as an adjunct OSAS therapy.

PMID- 21868709
TI  - Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in
      peripheral artery disease patients.
AB  - OBJECTIVE: Peripheral artery disease (PAD) is characterized by impaired blood
      flow to the lower extremities, causing claudication and exercise intolerance. The
      mechanism(s) by which exercise training improves functional capacity is not
      understood. This study tested the hypothesis that in PAD patients who undergo
      supervised exercise training, increases in capillary density (CD) in calf muscle
      take place before improvements in peak oxygen uptake (VO(2)). METHODS AND
      RESULTS: Thirty-five PAD patients were randomly assigned to 12 weeks of directly
      supervised or home-based exercise training. Peak VO(2) testing and gastrocnemius
      muscle biopsies were performed at baseline and after training. CD (endothelial
      cells/mm(2)) was measured using immunofluorescence staining. After 3 weeks of
      directly supervised training, patients had an increase in CD (216+/-66 versus
      284+/-77, P<0.01) but no increase in peak VO(2). However, after 12 weeks, peak
      VO(2) increased (15.3+/-2.8 versus 16.8+/-3.8, P<0.01), whereas in muscle, CD
      remained increased over baseline, but there were no changes in markers of
      oxidative capacity. Within subjects, CD was related to peak VO(2) before and
      after directly supervised training. CONCLUSION: Changes in CD in ischemic muscle
      with training may modulate the response to training, and those changes precede
      the increase in VO(2).

PMID- 21868708
TI  - Gain and loss of function for glutathione synthesis: impact on advanced
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Glutamate-cysteine ligase (GCL) is the rate-limiting step in
      glutathione synthesis. The enzyme is a heterodimer composed of a catalytic
      subunit, GCLC, and a modifier subunit, GCLM. We generated apolipoprotein E (apoE)
      /- mice deficient in GCLM (apoE-/-/Gclm-/-) and transgenic mice that overexpress
      GCLC specifically in macrophages (apoE-/-/Gclc-Tg) to test the hypothesis that
      significantly altering the availability of glutathione has a measurable impact on
      both the initiation and progression of atherosclerosis. METHODS AND RESULTS:
      Atherosclerotic plaque size and composition were measured in the innominate
      artery in chow-fed male and female mice at 20, 30, 40, and 50 weeks of age and in
      the aortic sinus at 40 and 50 weeks of age. The apoE-/-/Gclm-/- mice more rapidly
      developed complex lesions, whereas the apoE-/-/Gclc-Tg mice had reduced lesion
      development compared with the littermate apoE-/- control mice. Transplantation of
      bone marrow from the apoE-/-/Gclm-/- and apoE-/-/Gclc-Tg mice into apoE-/- mice
      with established lesions also stimulated or inhibited further lesion development
      at 30 weeks posttransplant. CONCLUSION: Gain and loss of function in the capacity
      to synthesize glutathione especially in macrophages has reciprocal effects on the
      initiation and progression of atherosclerosis at multiple sites in apoE-/- mice.

PMID- 21868713
TI  - Epidermal growth factor receptor signaling mediates vesicant-induced airway
      epithelial secretion of interleukin-6 and production of mucin.
AB  - The chemical warfare agent sulfur mustard (HD) and its analogue nitrogen mustard
      (HN2) are highly reactive vesicants that can cause airway epithelial injury.
      However, little is known about the mechanisms governing vesicant-related airway
      damage. This study assessed the role of epidermal growth factor receptor (EGFR)
      signaling in mediating the effects of exposure to vesicants on the secretion of
      cytokines and production of mucin in human airway epithelial cells. Normal human
      bronchial epithelial cells (NHBECs) at an air-liquid interface were challenged
      apically with either 200 MUM HN2 or medium alone (mock treatment, MT), and
      cultures were evaluated for receptor fate, the secretion of IL-6, and the
      production of both total mucin and Mucin 5AC (MUC5AC). Exposure to HN2 induced
      the activation of both EGFR and (44/42)mitogen-activated protein kinase
      ((44/42)MAPK), as well as the ubiquitination and colocalization of EGFR within
      lysosomal structures. Moreover, challenge with HN2 induced the up-regulation of
      IL-6 and MUC5AC at the mRNA and protein levels, and stimulated the secretion of
      total mucin in NHBECs. HN2-related effects on the secretion of IL-6 and the
      production of total mucin and MUC5AC were reversed by the selective EGFR
      inhibitor AG1478 and by an EGFR-blocking antibody. The HN2-induced activation of
      (44/42)MAPK and the up-regulation of IL-6 secretion in NHBECs were also largely
      reversed by a transforming growth factor-alpha (TGF-alpha)-blocking antibody and
      by the metalloprotease inhibitor GM 6001, suggesting that the HN2-related effects
      on EGFR signaling were TGF-alpha-dependent. Collectively, these findings suggest
      that EGFR signaling may play a significant role in mediating vesicant-induced
      airway epithelial injury.

PMID- 21868714
TI  - Application of yoga in residential treatment of traumatized youth.
AB  - BACKGROUND: The Trauma Center at Justice Resource Institute has adapted a form of
      Hatha yoga into a trauma-sensitive adjunctive component of intervention for use
      with complexly traumatized individuals exhibiting chronic affective and somatic
      dysregulation and associated behavioral, functioning, and health complaints.
      OBJECTIVES: This article explores the use of yoga with traumatized youth (aged 12
      21 years) in residential treatment. DESIGN: A review of the literature on the
      somatic impact of trauma exposure provides a rationale for the use of yoga with
      this population and highlights an emerging evidence base in support of this
      practice. Case vignettes illustrate the integration of structured, gentle yoga
      practices into residential programming for youth with severe emotional and
      behavioral problems. RESULTS: Anecdotal data and clinical observation underscore
      the promise of yoga as a viable approach to build self-regulatory capacity of
      traumatized youth. CONCLUSIONS: Future directions in the development and
      evaluation of trauma-informed yoga practices for youth are discussed.

PMID- 21868715
TI  - Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct
      thrombin inhibitor, with coadministration of digoxin.
AB  - This study evaluated the potential impact of concomitant digoxin on the
      pharmacokinetics and pharmacodynamics of dabigatran etexilate, a novel oral
      direct thrombin inhibitor. Healthy volunteers (n = 23) received 150 mg dabigatran
      etexilate twice daily on days 1 to 3 and once on day 4 in 1 period. Digoxin was
      given in another period as a loading dose of 0.5 mg early on day 1 and 0.25 mg in
      the evening of day 1 and on the mornings of days 2 to 4. In a third treatment
      period, dabigatran etexilate together with digoxin was given on days 1 to 4.
      Exposure to dabigatran was not significantly altered with concomitant digoxin-the
      maximum concentration (Cmax,ss ) and area under the concentration-time curve at
      steady state over 1 dosing interval (AUCtau,ss ) of dabigatran with and without
      digoxin were essentially unchanged. The pharmacokinetic profile of digoxin also
      remained unchanged in the presence of dabigatran etexilate. Dabigatran's
      anticoagulant effect, assessed by blood coagulation time assays, was not
      influenced by digoxin. Dabigatran etexilate and digoxin can be coadministered
      without the need for dose adjustment of either drug. 

PMID- 21868716
TI  - Assessment of the effects of renal impairment on the pharmacokinetics of the
      soluble guanylate cyclase activator cinaciguat after a single intravenous dose.
AB  - This open-label, parallel-group, single-dose study assessed the safety and
      pharmacokinetics of cinaciguat, a novel soluble guanylate cyclase activator in
      clinical development for the treatment of acute decompensated heart failure, in
      individuals with mild, moderate, or severe renal impairment compared with
      individuals with normal renal function. Cinaciguat was administered as a 100 ug/h
      continuous infusion over 4 hours. Plasma concentrations were determined by high
      performance liquid chromatography coupled with mass spectrometry. Renal function
      had only minor effects on the pharmacokinetics of cinaciguat. The apparent volume
      of distribution at steady state was slightly increased in individuals with renal
      impairment. The total body clearance from plasma showed a slight tendency to
      increase with progression of renal impairment, which can be explained by an
      increased hematocrit in individuals with renal impairment. No relevant influence
      was found on the terminal half-life. The fraction of cinaciguat unbound in plasma
      was very low (<1%) in all groups. Pharmacokinetic variability tended to be
      somewhat increased in individuals with renal impairment. Adverse events were
      mostly mild, and their incidence was similar in all groups. In conclusion,
      cinaciguat, a promising drug candidate for the treatment of acute decompensated
      heart failure, will not require dose adjustment based on renal function.

PMID- 21868717
TI  - Does erythromycin have anti-inflammatory effects independent of its antimicrobial
      action?

PMID- 21868719
TI  - Glycemic control and nutrition.

PMID- 21868718
TI  - Percutaneous endoscopic gastrostomy complication rates and compliance with the
      American Society for Gastrointestinal Endoscopy guidelines for the management of
      antithrombotic therapy.
AB  - BACKGROUND: The American Society for Gastrointestinal Endoscopy (ASGE) has
      published recommendations in regards to anticoagulant (AC) and antiplatelet (AP)
      therapy management during endoscopic procedures. So far, no study has assessed
      either ASGE recommendation compliance during percutaneous endoscopic gastrostomy
      (PEG) placement or procedure-associated complication rates as related to the
      observance of these recommendations. The aims of this study were to compare the
      incidence and type of complications during PEG placement in patients receiving or
      not receiving AC and/or AP therapy and to determine the compliance with ASGE's AC
      and AP management guidelines. METHODS: Medical files of patients who underwent
      PEG placement from January 2004 to December 2008 were reviewed. Clinical and
      procedure-related data were recorded. Patients were separated into 1 of 2 groups:
      patients under AP and/or AC therapy prior to PEG placement (n = 51) and a control
      group of patients (n = 40) not receiving any AP and/or AC treatment at least 6
      months prior to the procedure. RESULTS: A total of 91 patients (51 cases) were
      included. Groups were comparable in demographics and clinical characteristics. No
      differences in the frequency and type of complications were found between groups.
      ASGE's recommendations were not followed in any of these patients. CONCLUSIONS:
      Overall PEG placement complication rate was 13.7%. AP therapy may be safely
      discontinued closer to the time of endoscopic procedure than the time currently
      recommended by the ASGE guidelines.

PMID- 21868720
TI  - Influence of lipid type on bis (2-ethylhexyl)phthalate (DEHP) leaching from
      infusion line sets in parenteral nutrition.
AB  - BACKGROUND: Bis(2-ethylhexyl)phthalate (or DEHP) is widely used in polyvinyl
      chloride (PVC) tubings for its good plasticizing properties. Because it is not
      covalently bound to the plastic matrix, it is able to escape from PVC during the
      infusion of the lipid emulsions used in parenteral nutrition (PN). This creates a
      vector through which it can enter into contact with the patient via the nutrition
      admixtures infused. This study was designed to assess the potential role of the
      type of lipids used in PN admixtures on the quantity of DEHP leached out from PVC
      based tubings. METHODS: PVC-based infusion lines, 6 commercially available lipid
      emulsions, and their oil base components were left in direct contact, and the
      amount of DEHP leached was measured by liquid chromatography. RESULTS: After a 24
      hour exposure period, DEHP migration varied significantly (P = .0000152)
      according to lipid type. The olive oil-based emulsion Clinoleic leached the most
      DEHP (65.8 ug/mL intravenous fat emulsion), followed by the fish oil-based
      emulsion Omegaven (37.8 ug/mL). The soybean oil-based emulsions Intralipid,
      Medialipide, Lipidem, and Structolipid showed comparable performances, with DEHP
      leaching rates into the emulsion measured at 27.3, 27.8, 23.6, and 19.6 ug/mL,
      respectively. Results from the same experiments run on pure-form oils (soybean
      oil, olive oil, coconut oil, and cod liver oil) confirmed the influence of lipid
      type on DEHP leaching. CONCLUSION: The major DEHP leaching caused by olive oil
      based emulsions raises cause for concern because DEHP presents distinctive toxic
      effects, including an increased risk of cholestasis.

PMID- 21868721
TI  - Effects of walking speed and results of timed get-up-and-go tests on quality of
      life and social participation in elderly individuals with a history of
      osteoporosis-related fractures.
AB  - OBJECTIVE: To investigate the relationships between physical performance, quality
      of life (QoL), and social participation among elderly men and women with a
      history of osteoporosis-related fractures. METHOD: The study was a population
      based cross-sectional study including 155 participants aged 60 to 93 years from
      the Swedish longitudinal investigation, "Good Aging in Skane." The participants
      had suffered fracture of the vertebrae, hip, pelvis, or ankle. Physical
      performance was expressed as walking speed (WS) and timed get-up-and-go (TUG).
      QoL was measured as using the Health Related Quality of Life (HRQoL) and Life
      Satisfaction (LS) scales. Social participation was defined as taking part in
      social, cultural, and leisure activities. RESULTS: Lower WS and/or TUG were
      associated with lower HRQoL, lower LS, and a reduction in social participation,
      after adjustment for confounding factors. DISCUSSION: Measurements of WS and TUG
      could be used to determine QoL and social participation in elderly people having
      sustained fractures.

PMID- 21868722
TI  - Emergence of male-biased genes on the chicken Z-chromosome: sex-chromosome
      contrasts between male and female heterogametic systems.
AB  - There has been extensive traffic of male-biased genes out of the mammalian and
      Drosophila X-chromosomes, and there are also reports of an under-representation
      of male-biased genes on the X. This may reflect an adaptive process driven by
      natural selection where an autosomal location of male-biased genes is favored
      since male genes are only exposed to selection one-third of the time when X
      linked. However, there are several alternative explanations to "out-of-the-X"
      gene movement, including mutational bias and a means for X-linked genes to escape
      meiotic sex chromosome inactivation (MSCI) during spermatogenesis. As a critical
      test of the hypothesis that genomic relocation of sex-biased genes is an adaptive
      process, I examined the emergence, and loss, of genes on the chicken Z
      chromosome, i.e., a female heterogametic system (males ZZ, females ZW). Here, the
      analogous prediction would be an emergence of male-biased genes onto, not a loss
      from, the Z-chromosome because Z is found more often in males than autosomes are.
      I found that genes expressed in testis but not in ovary are highly over
      represented among genes that have emerged on the Z-chromosome during avian
      evolution. Moreover, genes with male-biased expression are similarly over
      represented among new Z-chromosomal genes. Interestingly, genes with female
      biased expression have more often moved from than to the Z-chromosome. These
      observations show that male and female heterogametic organisms display opposing
      directionalities in the emergence and loss of sex-biased genes on sex
      chromosomes. This is consistent with theoretical models on the evolution of
      sexually antagonistic genes in which new mutations are at least partly dominant.

PMID- 21868723
TI  - Comprehensive stroke centers overcome the weekend versus weekday gap in stroke
      treatment and mortality.
AB  - BACKGROUND AND PURPOSE: Hospital staffing may be reduced on weekends. Prior
      studies of weekend disparities in stroke care have focused on in-hospital
      mortality with variable results. We hypothesized that 90-day mortality was higher
      in patients with stroke hospitalized on weekends versus weekdays, and this
      difference has been minimized over time by improvements in organization and
      delivery of stroke care. METHODS: We used the Myocardial Infarction Data
      Acquisition System administrative database, which includes data on patients
      discharged with a primary diagnosis of cerebral infarction from all nonfederal
      acute care hospitals in New Jersey between 1996 and 2007. Out-of-hospital deaths
      were assessed by matching MIDAS records with New Jersey death registration files.
      New Jersey hospitals are designated by the state as comprehensive stroke centers,
      primary stroke centers, or nonstroke centers. The primary outcome measure was 90
      day all-cause mortality after hospital admission. RESULTS: A total of 134 441
      patients were admitted with a primary diagnosis of cerebral infarction during the
      study period. A total of 23.4% were admitted to a comprehensive stroke center,
      51.5% to a primary stroke center, and 25.1% to a nonstroke center. Ninety-day
      mortality was greater in patients with stroke admitted on weekends compared with
      weekdays (17.2% versus 16.5%; P=0.002). The adjusted risk of death at 90 days was
      significantly greater for weekend admission (hazard ratio, 1.05; 95% CI, 1.02 to
      1.09). No difference in 90-day mortality was observed for patients admitted to
      comprehensive stroke centers on weekends versus weekdays (hazard ratio, 1.01; 95%
      CI, 0.95 to 1.08). CONCLUSIONS: Patients with stroke admitted on weekends to New
      Jersey hospitals had a significantly higher risk of death by 90 days. No such
      difference in mortality was observed at comprehensive stroke centers.

PMID- 21868724
TI  - Comprehensive stroke centers: eliminating an apparent disparity in stroke care on
      weekends versus weekdays?

PMID- 21868725
TI  - High-intensity signal on time-of-flight magnetic resonance angiography indicates
      carotid plaques at high risk for cerebral embolism during stenting.
AB  - BACKGROUND AND PURPOSE: A major disadvantage of carotid artery stenting (CAS)
      compared to carotid endarterectomy is the increased risk of cerebral embolism.
      Thus, establishing a simple method to discriminate fragile plaques on
      preoperative routine examination is important. The present study examined whether
      high-intensity signal (HIS) in the plaque on time-of-flight (TOF) MRA, performed
      for screening, can discriminate plaque at high risk for cerebral embolism during
      CAS. METHODS: In the 30 patients treated using carotid endarterectomy,
      relationships between pathological findings of the plaques and TOF-MRA findings
      were analyzed. In the 112 patients treated using CAS, postoperative ipsilateral
      ischemic lesions on diffusion-weighted imaging and periprocedural ischemic
      symptoms were analyzed. RESULTS: The percentage area of intraplaque hemorrhage
      stained by glycophorin A was significantly larger in HIS-positive plaques
      (51.8%+/-9.8%) than in HIS-negative plaques (8.6%+/-9.4%; P<0.001). Postoperative
      ischemic lesions on diffusion-weighted imaging were more frequent in the HIS
      positive plaques (25/38; 65.8%) than in the HIS-negative plaques (26/74; 35.1%;
      P=0.002). Periprocedural ischemic symptoms were more frequently observed in HIS
      positive plaques (7/38; 18.4%) than in HIS-negative plaques (1/74; 1.4%;
      P=0.003). Multivariate logistic regression analysis identified HIS on TOF-MRA as
      an independent predictor of periprocedural ischemic symptoms (odds ratio, 15.08;
      95% confidence interval, 1.76-129.0). CONCLUSIONS: HIS in the plaque on TOF-MRA
      performed for screening could discriminate plaques at high risk for cerebral
      embolism during CAS.

PMID- 21868726
TI  - Acute pediatric stroke: contributors to institutional cost.
AB  - BACKGROUND AND PURPOSE: Recent studies examined the overall cost of pediatric
      stroke, but there are little data regarding the sources of these costs. We
      examined an administrative database that collected charges from 24 US children's
      hospitals to determine the sources of costs for acute hospital care of stroke.
      METHODS: We used International Classification of Diseases, 9th Revision codes to
      search the Pediatric Health Information System. From 2003 to 2009 there were 1667
      patients who had a primary diagnosis of stroke, 703 of which were hemorrhagic and
      964 were ischemic. Individual costs, excluding physician charges, were gathered
      under 7 categories that were ranked to determine which contributed the most to
      total cost. Individual costs were ranked within their categories. We analyzed
      costs based on stroke type. Total costs were adjusted using the US Consumer Price
      Index to compare increases with the rate of inflation. RESULTS: Median total cost
      for any stroke was $19,548 (interquartile range, $10,764-$40,721). The category
      "other/nursing" contributed the most to hospital costs followed by imaging,
      laboratory, and pharmacy. Brain MRI and CT contributed the most to imaging costs.
      Hemorrhagic strokes (median $24,843) were more expensive than ischemic strokes
      (median $16,954). Total cost increased from 2003 to 2009, but no overall annual
      trend emerged after controlling for gender, age, race, and hospital. CONCLUSIONS:
      This is the first in-depth analysis of cost for pediatric stroke care. The
      highest cost categories are potential targets for cost containment but are also
      crucial for effective diagnosis and treatment. Necessary yet prudent use of
      imaging technologies and inpatient stays may be strategies for cost containment.

PMID- 21868728
TI  - Ancrod and fibrin formation: perspectives on mechanisms of action.
AB  - BACKGROUND AND PURPOSE: Ancrod, derived from Malayan pit viper venom, has been
      tested as ischemic stroke treatment in clinical trials with inconsistent results.
      We studied the actions of ancrod on fibrinolysis pathways in patient plasma
      samples and endothelial cell culture systems. METHODS: We analyzed fibrinogen
      levels during the first 6 hours of ancrod infusion in patients entered in the
      Stroke Treatment with Ancrod Trial. For the in vitro study, human brain
      microvascular endothelial cells incubated with plasminogen or with human brain
      microvascular endothelial cell-conditioned medium were co-incubated with ancrod
      and fibrinogen under normal or oxygen-glucose deprivation conditions over 6
      hours. RESULTS: Fibrinogen levels decreased both in vivo and in vitro. Ancrod
      generated fibrinopeptide A, caused visible clot formation, and reduced levels of
      tissue-type plasminogen activator antigen in the human brain microvascular
      endothelial cell system and in a cell-free system with conditioned media.
      CONCLUSIONS: The in vitro results indicate that ancrod causes local fibrin
      formation and secondary depletion of tissue-type plasminogen activator by binding
      to fibrin clot. Ancrod-induced fibrin formation could result in cerebral
      microvascular occlusion and may explain the suboptimal clinical effects of ancrod
      in human stroke trials.

PMID- 21868727
TI  - Revised and updated recommendations for the establishment of primary stroke
      centers: a summary statement from the brain attack coalition.
AB  - BACKGROUND AND PURPOSE: The formation and certification of Primary Stroke Centers
      has progressed rapidly since the Brain Attack Coalition's original
      recommendations in 2000. The purpose of this article is to revise and update our
      recommendations for Primary Stroke Centers to reflect the latest data and
      experience. METHODS: We conducted a literature review using MEDLINE and PubMed
      from March 2000 to January 2011. The review focused on studies that were relevant
      for acute stroke diagnosis, treatment, and care. Original references as well as
      meta-analyses and other care guidelines were also reviewed and included if found
      to be valid and relevant. Levels of evidence were added to reflect current
      guideline development practices. RESULTS: Based on the literature review and
      experience at Primary Stroke Centers, the importance of some elements has been
      further strengthened, and several new areas have been added. These include (1)
      the importance of acute stroke teams; (2) the importance of Stroke Units with
      telemetry monitoring; (3) performance of brain imaging with MRI and diffusion
      weighted sequences; (4) assessment of cerebral vasculature with MR angiography or
      CT angiography; (5) cardiac imaging; (6) early initiation of rehabilitation
      therapies; and (7) certification by an independent body, including a site visit
      and disease performance measures. CONCLUSIONS: Based on the evidence, several
      elements of Primary Stroke Centers are particularly important for improving the
      care of patients with an acute stroke. Additional elements focus on imaging of
      the brain, the cerebral vasculature, and the heart. These new elements may
      improve the care and outcomes for patients with stroke cared for at a Primary
      Stroke Center.

PMID- 21868729
TI  - High levels of apolipoprotein B/AI ratio are associated with intracranial
      atherosclerotic stenosis.
AB  - BACKGROUND AND PURPOSE: The apolipoprotein B (apoB)/apoAI ratio is recognized as
      a better indicator of cardiovascular disease than other cholesterol measures.
      Whether intracranial or extracranial atherosclerosis is more closely associated
      with an increased apoB/apoAI ratio has not been investigated. METHODS: A total of
      464 statin or fibrate naive Korean patients with acute ischemic stroke was
      categorized into 3 groups: intracranial (ICAS, n=236), extracranial (n=44), and
      no cerebral atherosclerotic stenosis (n=184). The apoB/apoAI ratio and
      demographics, including the presence of metabolic syndrome, were compared among
      the groups. RESULTS: The ICAS group showed a higher apoB/apoAI ratio (0.81+/
      0.02) than both the extracranial atherosclerotic stenosis (0.74+/-0.03) and no
      cerebral atherosclerotic stenosis (0.72+/-0.02) groups (P=0.002). The ratio was
      substantially increased (0.93+/-0.03) in patients with advanced ICAS (>=3
      intracranial stenoses). With a multivariable analysis, the highest apoB/apoAI
      ratio quartile was an independent predictor of ICAS (OR, 2.13; 95% CI, 1.05 to
      4.33). A dose-response relationship was observed between the presence of advanced
      ICAS and the apoB/apoAI ratio quartiles (OR, 4.03; 95% CI, 1.26 to 12.88 for the
      second quartile; OR, 4.88; 95% CI, 1.54 to 15.49 for the third quartile; and OR,
      7.79; 95% CI, 2.41 to 25.16 for the fourth quartile when referenced to the first
      quartile). Patients having more metabolic syndrome components were more likely to
      have ICAS, advanced ICAS, and a higher apoB/apoAI ratio (P<0.001 for all).
      CONCLUSIONS: A higher apoB/apoAI ratio is a predictor of ICAS rather than of
      extracranial atherosclerotic stenosis or no cerebral atherosclerotic stenosis.
      The apoB/apoAI ratio might be a biomarker for ICAS in Asian patients with stroke.

PMID- 21868731
TI  - CLEAR intraventricular hemorrhage: more than a glimmer of hope.

PMID- 21868730
TI  - Low-dose recombinant tissue-type plasminogen activator enhances clot resolution
      in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial.
AB  - BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage and
      intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated
      a clot lytic treatment strategy for these patients in terms of mortality,
      ventricular infection, and bleeding safety events, and for its effect on the rate
      of intraventricular clot lysis. METHODS: Forty-eight patients were enrolled at 14
      centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen
      activator (rtPA) or placebo. Demographic characteristics, severity factors,
      safety outcomes (mortality, infection, bleeding), and clot resolution rates were
      compared in the 2 groups. RESULTS: Severity factors, including admission Glasgow
      Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume,
      and blood pressure were evenly distributed, as were adverse events, except for an
      increased frequency of respiratory system events in the placebo-treated group.
      Neither intracranial pressure nor cerebral perfusion pressure differed
      substantially between treatment groups on presentation, with external ventricular
      device closure, or during the active treatment phase. Frequency of death and
      ventriculitis was substantially lower than expected and bleeding events remained
      below the prespecified threshold for mortality (18% rtPA; 23% placebo),
      ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo,
      which approached statistical significance; P=0.1). The median duration of dosing
      was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial
      effect of rtPA on rate of clot resolution. CONCLUSIONS: Low-dose rtPA for the
      treatment of intracerebral hemorrhage with intraventricular hemorrhage has an
      acceptable safety profile compared to placebo and historical controls. Data from
      a well-designed phase III clinical trial, such as CLEAR III, will be needed to
      fully evaluate this treatment.

PMID- 21868732
TI  - Higher incidence of in-hospital complications in patients with clipped versus
      coiled ruptured intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: After aneurysmal subarachnoid hemorrhage (SAH), patients
      with clipped aneurysms have a higher incidence of neurocognitive deficits and
      seizures compared with patients with coiled aneurysms. It remains unknown if
      patients with clipped aneurysms also have a higher incidence of other in-hospital
      complications. METHODS: We used data from the Registry of the Canadian Stroke
      Network on consecutive patients admitted to hospital with aneurysmal SAH.
      Patients who died within 2 days after admission were excluded. Baseline
      characteristics, incidence of various in-hospital complications within 30 days
      after admission, length of stay, poor functional outcome (modified Rankin Scale
      score at discharge of >=3), and mortality were compared between patients with
      clipped versus coiled aneurysms. RESULTS: Of the 931 patients, 548 (59%) were
      clipped and 383 (41%) coiled. Baseline characteristics were similar. Compared
      with patients with coiled aneurysms, patients with clipped aneurysms had a higher
      incidence of in-hospital complications (37.2% versus 24.5% of patients;
      P<0.0001), poor functional outcome at discharge (69.4% versus 51.4%; P<0.0001),
      mortality (at discharge: 14.6% versus 9.1%; P=0.01), and a longer length of stay
      (17 [interquartile range, 11 to 29] versus 13 [interquartile range, 7 to 22]
      days; P<0.0001). Higher incidences were observed for urinary tract infection
      (P=0.02), pneumonia (P=0.01), cardiac/respiratory arrest (P=0.007), seizure
      (P=0.01), and decubitus ulcer (P=0.02). Urinary tract infection, pneumonia,
      cardiac/respiratory arrest, and seizure were independent predictors of poor
      functional outcome. CONCLUSIONS: Patients with clipped aneurysms have a higher
      incidence of in-hospital complications than patients with coiled aneurysms, which
      attributes to a higher risk of poor functional outcome and death and an increased
      length of stay.

PMID- 21868734
TI  - Letter by Shenhar-Tsarfaty et al regarding article, "Autonomic shift and
      increased susceptibility to infections after acute intracerebral hemorrhage".

PMID- 21868733
TI  - Replication study of chr17q25 with cerebral white matter lesion volume.
AB  - BACKGROUND AND PURPOSE: Recently, the first genomewide association study on
      cerebral white matter lesion burden identified chr17q25 to be significantly
      associated with white matter lesions. We report on the first independent
      replication study of this genetic association. METHODS: In a population-based
      cohort study, we investigated the association between the 6 genomewide
      significant single nucleotide polymorphisms at that locus and cerebral white
      matter lesion volume on MRI, measured quantitatively, adjusted for age, sex, and
      intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk
      factors were evaluated separately. Finally, we performed a meta-analysis of all
      published data for the single most significant single nucleotide polymorphism,
      rs3744028. RESULTS: The risk alleles of all the 6 single nucleotide polymorphisms
      were significantly associated with white matter lesion volume with P=1.1*10(-3)
      for rs3744028, adjusted for age, sex, and intracranial volume. Additional
      adjustments only had minor influence on these associations. A meta-analysis with
      all published data for rs3744028 resulted in a probability value of 5.3*10(-17).
      CONCLUSIONS: This study further establishes chr17q25 as a novel genetic locus for
      WML volume.

PMID- 21868735
TI  - Relations of blood inflammatory marker levels with cerebral microbleeds.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) are observed in the elderly
      and have been regarded as one of the manifestations of small vessel disease.
      Although inflammatory processes have attracted much attention not only in large
      artery disease, but also in small vessel disease, their involvement in CMB
      remains to be determined. The purpose of this study is to clarify relations
      between inflammatory marker levels and CMB. METHODS: Four hundred thirty-one
      patients without histories of cerebrovascular diseases were prospectively
      enrolled. The presence and number of CMB were assessed on gradient-echo magnetic
      resonance imaging. As common inflammatory markers, serum levels of high
      sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-18
      (IL-18) were evaluated. RESULTS: CMB were found in 65 patients (15%). In 35
      patients, at least one CMB was found in deep locations, but 30 patients had
      strictly lobar CMB. Levels of hsCRP, IL-6, and IL-18 were higher in patients with
      CMB than in those without. Logistic regression analyses showed that each 1SD
      increase in each inflammatory marker level was significantly associated with the
      presence of CMB after adjustment for age and sex, and after additional adjustment
      for cardiovascular risk factors, silent lacunar infarction, and white matter
      hyperintensity. The OR (95% CI) of hsCRP, IL-6, and IL-18 was 1.81 (1.35-2.46),
      1.73 (1.18-2.61), and 2.41 (1.44-4.52), respectively. Furthermore, the
      inflammatory marker levels were associated with both deep and lobar CMB.
      CONCLUSIONS: Higher levels of hsCRP, IL-6, and IL-18 are associated with CMB, in
      both deep and lobar locations, suggesting the involvement of inflammation in CMB.

PMID- 21868737
TI  - In-hospital medical complications, length of stay, and mortality among stroke
      unit patients.
AB  - BACKGROUND AND PURPOSE: The relationship between in-hospital stroke-related
      medical complications and clinical outcome remains unclear. We examined whether
      medical complications were associated with length of stay (LOS) and mortality
      among stroke unit patients. METHODS: Using population-based Danish medical
      registries, we performed a follow-up study among all patients with acute stroke
      admitted to stroke units in 2 counties between 2003 and 2009 (n=13 721). Data
      regarding in-hospital medical complications, including pneumonia, urinary tract
      infection, pressure ulcer, falls, deep venous thrombosis, pulmonary embolism, and
      severe constipation together with LOS and mortality were prospectively
      registered. RESULTS: Overall, 25.2% of patients (n=3453) experienced 1 or more
      medical complications during hospitalization. The most common complications were
      urinary tract infection (15.4%), pneumonia (9.0%), and constipation (6.8%).
      Median LOS was 13 days (25th and 75th quartiles, 5 and 33). All medical
      complications were associated with longer LOS. The adjusted relative LOS
      extension ranged from 1.80 (95% CI, 1.54-2.11) for pneumonia to 3.06 (95% CI,
      2.67-3.52) for falls. Patients with 1 or more complications had an increased 1
      year mortality rate (adjusted mortality rate ratio [MRR], 1.20; 95% CI, 1.04
      1.39). The association was mainly because of pneumonia, which was associated with
      higher mortality both after 30 days (adjusted MRR, 1.59; 95% CI, 1.31-1.93) and 1
      year (adjusted MRR, 1.76; 95% CI, 1.45-2.14). CONCLUSIONS: In-hospital medical
      complications were associated with longer LOS and some, in particular pneumonia,
      also with an increased mortality among patients with acute stroke.

PMID- 21868736
TI  - Increased frequency of first-episode poststroke depression after discontinuation
      of escitalopram.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare escitalopram,
      problem-solving therapy, and placebo to prevent poststroke depression during 6
      months after discontinuation of treatment. METHODS: We examined for depression 33
      patients assigned to placebo, 34 to escitalopram, and 41 to problem-solving
      therapy. RESULTS: After controlling for age, gender, prior mood disorder, and
      severity of stroke, new-onset major depression and Hamilton Depression scores
      were significantly higher 6 months after escitalopram was discontinued compared
      with the problem-solving therapy or placebo groups. CONCLUSIONS: Discontinuation
      of escitalopram may increase poststroke depressive symptoms.

PMID- 21868738
TI  - Clinical and MRI predictors of no early recanalization within 1 hour after tissue
      type plasminogen activator administration.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to investigate
      independent clinical and MRI factors associated with no early recanalization
      within 1 hour after tissue-type plasminogen activator (tPA) administration.
      METHODS: Patients with acute stroke within 3 hours of onset who were treated with
      tPA were studied prospectively. Patients with internal carotid artery, M1, and M2
      occlusion were enrolled, and independent clinical and MRI factors associated with
      no early recanalization within 1 hour after tPA administration were examined
      using multivariate logistic regression analysis. RESULTS: One hundred thirty-two
      patients (63 men; mean age, 76.4+/-10.2 years; internal carotid artery occlusion
      in 37 patients, M1 occlusion in 58, and M2 occlusion in 37) were enrolled. Follow
      up MR angiography within 60 minutes after tPA infusion revealed early
      recanalization in 49 (37.1%) patients (complete in 16 patients, partial in 33)
      and no recanalization in 83 (62.9%). Using 8 variables (atrial fibrillation, time
      from stroke onset to treatment >=140 minutes, use of warfarin, glucose >=135
      mg/dL, large artery diseases, internal carotid artery occlusion, M1 occlusion,
      and M1 susceptibility vessel sign on T2*) identified on univariate analysis at
      P<0.2, multivariate logistic regression analysis revealed that M1 susceptibility
      vessel sign was the only independent factor associated with no early
      recanalization (OR, 7.157; 95% CI, 1.756 to 29.172; P=0.006). The sensitivity,
      specificity, positive predictive value, and negative predictive value of M1
      susceptibility vessel sign for predicting no early recanalization were 31.3%,
      93.9%, 89.7%, and 44.7%, respectively. CONCLUSIONS: Of clinical and MRI factors
      before tPA infusion, M1 susceptibility vessel sign on T* is the only independent
      factor associated with no early recanalization within 1 hour after tPA
      administration.

PMID- 21868739
TI  - Cerebral small vessel disease and risk of death, ischemic stroke, and cardiac
      complications in patients with atherosclerotic disease: the Second Manifestations
      of ARTerial disease-Magnetic Resonance (SMART-MR) study.
AB  - BACKGROUND AND PURPOSE: Cerebral small vessel disease may be related to vascular
      and nonvascular pathology. We assessed whether lacunar infarcts and white matter
      lesions on MRI increased the risk of vascular and nonvascular death and future
      vascular events in patients with atherosclerotic disease. METHODS: Brain MRI was
      performed in 1309 patients with atherosclerotic disease from the Second
      Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Infarcts
      were scored visually and volumetric assessment of white matter lesion was
      performed. Patients were followed for a median of 4.5 years (range, 0.2 to 7.1
      years) for death, ischemic stroke, and ischemic cardiac complications. RESULTS:
      Cox regression models showed that presence of lacunar infarcts (n=229) increased
      the risk of vascular (hazard ratio, 2.6; 95% CI, 1.4 to 4.9) and nonvascular
      death (hazard ratio, 2.7; 95% CI, 1.3 to 5.3), adjusted for age, sex, vascular
      risk factors, nonlacunar infarcts, and white matter lesion. These risks were
      similar for patients with silent lacunar infarcts. White matter lesion volume
      (relative to total intracranial volume) increased the risk of vascular death
      (hazard ratio per milliliter increase, 1.03; 95% CI, 1.01 to 1.05) and white
      matter lesions in the upper quintile compared with lower quintiles increased risk
      of ischemic stroke (hazard ratio, 2.6; 95% CI, 1.3 to 4.9). CONCLUSIONS: Cerebral
      small vessel disease, with or without a history of cerebrovascular disease, is
      associated with increased risk of death and ischemic stroke in patients with
      atherosclerotic disease.

PMID- 21868740
TI  - Nicotine replacement therapy after subarachnoid hemorrhage is not associated with
      increased vasospasm.
AB  - BACKGROUND AND PURPOSE: A significant number of patients with aneurysmal
      subarachnoid hemorrhage are active smokers and at risk for acute nicotine
      withdrawal. There is conflicting literature regarding the vascular effects of
      nicotine and theoretical concern that it may worsen vasospasm. The literature on
      the safety of nicotine replacement therapy and its effects on vasospasm is
      limited. METHODS: A retrospective analysis was conducted of a prospectively
      collected database of aneurysmal subarachnoid hemorrhage patients admitted to the
      neurointensive care unit from 1994 to 2008. Paired control subjects matched for
      age, sex, Fisher score, aneurysm size and number, hypertension, and current
      medication were analyzed. The primary outcome was clinical and angiographic
      vasospasm and the secondary outcome was Glasgow Outcome Score on discharge.
      Conditional logistic models were used to investigate univariate and multivariate
      relationships between predictors and outcome. RESULTS: Two hundred fifty-eight
      active smoking patients were included of which 87 were treated with transdermal
      nicotine replacement therapy. Patients were well matched for age, sex, gender,
      Fisher score, aneurysm size and number, hypertension, and current medications,
      but patients who received nicotine replacement therapy had less severe Hunt-Hess
      scores and Glasgow coma scores. There was no difference in angiographic
      vasospasm, but patients who received nicotine replacement therapy were less
      likely to have clinical vasospasm (19.5 versus 32.8%; P=0.026) and a Glasgow
      Outcome Score <4 on discharge (62.6% versus 81.6%; P=0.005) on multivariate
      analysis. CONCLUSIONS: Nicotine replacement therapy was not associated with
      increased angiographic vasospasm and was associated with less clinical vasospasm
      and better Glasgow Outcome Score scores on discharge.

PMID- 21868741
TI  - Two-hour improvement of patients in the National Institute of Neurological
      Disorders and Stroke trials and prediction of final outcome.
AB  - BACKGROUND AND PURPOSE: Ongoing clinical trials are using early response to
      intravenous tissue-type plasminogen activator (tPA) to stratify patients into
      endovascular therapies. Little is known about the likelihood of early recovery
      and its correlation with final stroke outcome. METHODS: We analyzed the National
      Institute of Neurological Disorders and Stroke tPA dataset for patients with
      early improvement (EI), a change of >=4, or score 0 on the 2-hour National
      Institutes of Health Stroke Scale (NIHSS) to predict good 90-day outcome. We
      adjusted for multiple confounders and divided the patients by baseline NIHSS
      score 0 to 10, 11 to 20, >20, and stroke type to analyze if EI predicted good
      outcome across stroke severities and types. We analyzed different EI thresholds
      to identify the best level of NIHSS change to predict good 90-day outcome using a
      receiver-operator characteristic curve. RESULTS: In total, 183 of 624 (29.3%)
      patients had EI, 112 of 312 (35.9%) in the tPA group had EI, and 71 of 312
      (22.7%) in the placebo group had EI (P<0.0001). Smokers (P=0.012) and patients
      treated in <90 minutes (P=0.008) were more likely to have EI; diabetic patients
      (P=0.023) were less likely to show EI. The baseline NIHSS (mean+/-SD) of patients
      with EI was 16.1+/-6.5 versus 14.3+/-7.4 (P=0.001). A 90-day modified Rankin
      Scale score of 0 to 1 was achieved in 68 of 112 (60.7%) tPA-treated patient with
      EI and 65 of 200 (32.5%) without (placebo groups 30 of 71 [42.3%] versus 53/241
      [22.0%]). The adjusted odds ratio for good outcome was 1.71 (95% confidence
      interval [CI], 1.1-2.6; P=0.011) for tPA treatment and 7.69 (95% CI, 4.63-12.76;
      P<0.0001) for early improvement. EI predicted good outcome in patients with
      cardioembolic (13.6; 95% CI, 3.6-51.5) and small vessel (6.98; 95% CI, 2.86
      17.03), but not large vessel stroke (1.82; 95% CI, 0.38-8.59). The receiver
      operator characteristic curve showed that a threshold of 4 on the NIHSS for
      prediction of good outcome had a sensitivity of 84% and 36% specificity.
      CONCLUSIONS: Early improvement was more common in tPA-treated patients and was
      associated with good 90-day outcome. Whereas 32.5% of nonresponders after tPA had
      a good 90-day outcome, the use of EI to predict stroke outcome shows value.

PMID- 21868743
TI  - Arterial erectile dysfunction: reliability of penile Doppler evaluation
      integrated with serum concentrations of late endothelial progenitor cells and
      endothelial microparticles.
AB  - We recently showed the diagnostic value of a new immunophenotype of blood 
      endothelial progenitor cells (EPC)  (CD45(-)/CD34(+)/CD144(+)) and endothelial 
      microparticles (EMP) (CD45(-)/CD144(+)/annexin  V(+)) in patients with arterial
      erectile dysfunction (AED),  particularly in patients with associated late-onset
      hypogonadism and/or  metabolic syndrome. In addition, we evaluated the effects of
      androgen  replacement therapy, aerobic physical activity, and tadalafil
      administration  on these markers. The aim of this study was to evaluate the serum
      concentrations of EPCs and EMPs in a large cohort of patients with AED 
      according to severity of cavernous arterial insufficiency evaluated by penile 
      Doppler. A total of 120 patients (aged 58.0 +/- 6.0 years) with AED were 
      enrolled in this study. Patients were classified into 3 groups based on value  of
      peak systolic velocity (PSV). Group A: 37 patients with PSV <25 cm/s  (severe
      arterial insufficiency); group B: 40 patients with PSV between 25 and  29 cm/s
      (moderate arterial insufficiency); group C: 43 patients with PSV  between 30 and
      34 cm/s (mild arterial insufficiency). Twenty patients (aged  60.0 +/- 3.0 years)
      with psychogenic erectile dysfunction (PED)  represented the control group. EPC
      and EMP blood concentrations were evaluated  by flow cytometry. Patients with AED
      had significantly higher blood pressure,  triglyceride levels, homeostasis model
      assessment index of insulin resistance,  cavernous artery acceleration time, and
      intima-media thickness than those with  PED, whereas International Index of
      Erectile Function score, high-density  lipoprotein cholesterol level, and
      cavernous artery PSV were lower than those  in PED. Both EPC and EMP levels were
      significantly higher in patients with AED  compared with patients with PED. Among
      3 groups of patients with AED, there  were no significant differences in
      metabolic parameters examined, but group A  showed significantly higher values of
      cavernous artery acceleration time and  intima-media thickness than group B and
      group C. Finally, group A showed serum  concentrations of EPCs and EMPs
      significantly higher compared with other  groups with AED. Patients with AED
      showed worse metabolic parameters,  cavernous artery parameters, and EPC and EMP
      levels compared with patients  with PED. Among patients with AED, those with PSV
      <25 cm/s showed worse  findings of endothelial dysfunction. This suggests that
      AED is an expression  of endothelial damage and that this original
      immunophenotype of EPCs and EMPs  may be considered a predictor of endothelial
      dysfunction in patients with AED.  Finally, this study confirmed the reliability
      of penile Doppler evaluation  integrated with these serum markers of endothelial
      dysfunction.

PMID- 21868742
TI  - Safety and tolerability of deferoxamine mesylate in patients with acute
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Treatment with the iron chelator, deferoxamine mesylate
      (DFO), improves neurological recovery in animal models of intracerebral
      hemorrhage (ICH). We aimed to evaluate the feasibility, safety, and tolerability
      of varying dose-tiers of DFO in patients with spontaneous ICH, and to determine
      the maximum tolerated dose to be adopted in future efficacy studies. METHODS:
      This was a multicenter, phase-I, dose-finding study using the Continual
      Reassessment Method. DFO was administered by intravenous infusion for 3
      consecutive days, starting within 18 hours of ICH onset. Subjects underwent
      repeated clinical assessments through 90 days, and computed tomography
      neuroimaging pre- and post-drug-administration. RESULTS: Twenty subjects were
      enrolled onto 5 dose tiers, starting with 7 mg/kg per day and ending with 62
      mg/kg per day as the maximum tolerated dose. Median age was 68 years (range, 50
      90); 60% were men; and median Glasgow Coma Scale and National Institutes of
      Health Stroke Scale scores on admission were 15 (5-15) and 9 (0-39),
      respectively. ICH location was lobar in 40%, deep in 50%, and brain stem in 10%;
      intraventricular hemorrhage was present in 15%. DFO was discontinued because of
      adverse events in 2 subjects (10%). Six subjects (30%) experienced 12 serious
      adverse events, none of which were drug-related. DFO infusions were associated
      with mild blood-pressure-lowering effects. Fifty percent of patients had modified
      Rankin scale scores <=2, and 39% had modified Rankin scale scores of 4 to 6 on
      day 90; 15% died. CONCLUSIONS: Consecutive daily infusions of DFO after ICH are
      feasible, well-tolerated, and not associated with excessive serious adverse
      events or mortality. Our findings lay the groundwork for future studies to
      evaluate the efficacy of DFO in ICH.

PMID- 21868744
TI  - Male accessory gland infection frequency in infertile patients with chronic
      microbial prostatitis and irritable bowel syndrome: transrectal ultrasound
      examination helps to understand the links.
AB  - The aim of this study was to evaluate the frequency of male accessory gland 
      infection (MAGI) in patients with chronic bacterial prostatitis (CBP) plus 
      irritable bowel syndrome (IBS) and to compare the sperm parameters of patients 
      with or without MAGI. In addition, another objective of this study was to 
      evaluate the ultrasound characterization of the anatomical space between the 
      posterior wall of the prostate and the anterior wall of the rectum using 
      transrectal ultrasonography. Fifty consecutive patients with the following 
      criteria were enrolled: 1) infertility, 2) diagnosis of CBP, and 3) diagnosis  of
      IBS according to the Rome III criteria. The following 2 age-matched control 
      groups were also studied: infertile patients with CBP alone (n = 56) and  fertile
      men (n = 30) who had fathered a child within the previous 3 months.  Patients and
      controls underwent an accurate patient history; administration of  the National
      Institutes of Health-Chronic Prostatitis Symptom Index and  the Rome III
      questionnaires for prostatitis and IBS, respectively; physical  examination;
      semen analysis; and transrectal ultrasound evaluation (limited to  patients with
      CBP and IBS or CBP alone). A significantly higher frequency of  MAGI was found in
      patients with CBP plus IBS (82.0%) compared with patients  with CBP alone (53.6%)
      or fertile men (0%). The presence of MAGI in patients  with CBP plus IBS was
      associated with a significantly lower sperm  concentration, total number, and
      forward motility, and with a higher seminal  leukocyte concentration compared
      with patients with CBP alone and MAGI. Sperm  normal morphology was similar in
      the groups of patients. All sperm parameters  did not differ significantly in
      both groups of patients without MAGI. With  ultrasound evaluation, a
      significantly higher frequency of dilatation of  prostatic venous plexus was
      found in patients with CBP plus IBS (75%) compared  with patients with CBP alone
      (10%). Patients with CBP plus IBS had a  significantly higher frequency of MAGI
      compared with patients with CBP alone.  This was associated with worse sperm
      parameters and, hence, poorer  reproductive prognosis. We suggest searching for
      the presence of IBS in  patients with prostatitis syndrome, in particular when
      CBP and/or worse sperm  parameters are present. Finally, this is the first
      observation on ultrasound  examination of the anatomical space between the
      posterior wall of the prostate  and the anterior wall of the rectum reported in
      patients with CBP and IBS.  Further studies should clarify the meaning of the
      ultrasound findings.

PMID- 21868745
TI  - Cathepsin D in human reproductive tissues: cellular localization in testis and
      epididymis and surface distribution in different sperm conditions.
AB  - Mammalian sperm surface antigens are acquired either during spermatogenesis  or
      sperm maturation in the epididymis. These antigens, many of which are  hydrolytic
      enzymes, are actively synthesized and secreted by the resident  epithelial cells
      and adsorbed to the sperm membrane as part of posttesticular  sperm modification.
      In this study, we aimed to investigate the expression of  cathepsin-D (CAT-D) in
      human reproductive tissues and its distribution on the  sperm surface in
      different sperm conditions. Immunohistochemical results  revealed the expression
      of CAT-D in the somatic Sertoli and Leydig cells  without showing any
      immunoreactivity in any germ cells, despite their  engagement of the acrosomal
      system. A strong immunoreactivity of  anti-CAT-D was also detected in the
      epididymal epithelium, chiefly in  the principal cells, which are known to
      actively synthesize and secrete  proteins into the epididymal lumen. The absence
      of CAT-D in the clear cells  was unexpected because these cells are known to
      engage the endosomal  machinery. We further showed that CAT-D was anchored on the
      sperm surface  confined to the postacrosomal region without any lateral
      redistribution within  the membrane during sperm capacitation. However, the
      enzyme underwent changes  to be an active form of a 29/30-kd doublet during sperm
      capacitation. Using  CAT-D as a marker, we were able to demonstrate here
      localization of the enzyme  in human reproductive tissues, as well as reveal
      membrane modification in  human sperm during maturation and capacitation
      processes.

PMID- 21868746
TI  - Pharmacokinetics of modified slow-release oral testosterone over 9 days in normal
      men with experimental hypogonadism.
AB  - Oral administration of testosterone has potential use for the treatment of 
      hypogonadism. We have recently demonstrated that a novel formulation of oral 
      testosterone transiently normalized serum testosterone in a single-dose 
      pharmacokinetic study. In this report, we present the steady-state 
      pharmacokinetics of this formulation. Twelve healthy young men were rendered 
      hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 
      MUg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times 
      daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol,  and
      sex hormone-binding globulin (SHBG) were measured before and 1, 2,  4, 5, 6, 8,
      10, 11, 12, 14, 16, and 24 hours on the first and ninth day of  dosing. Before
      testosterone administration, all men had serum testosterone  under 75 ng/dL. Over
      day 1, the 24-hour average (geometric mean [%CV]) serum  total testosterone was
      378 (45) ng/dL. This decreased to 315 (41) ng/dL after  9 days of continuous
      treatment (P = .1 compared with day 1). The  24-hour average serum SHBG was 27
      (46) nmol/L on day 1 and was significantly  reduced to 19 (47) nmol/L by day 9 (P
      < .01). As a result, the  calculated free testosterone values were similar
      between day 1 and day 9: 8.7  (43) and 8.3 (37) ng/dL, respectively. DHT was in
      the reference range and  estradiol was slightly below on day 9. Oral testosterone
      (300 mg) dosed 3  times daily normalized serum testosterone in men with
      experimentally induced  hypogonadism after 9 days of dosing and significantly
      suppressed SHBG. This  formulation of oral testosterone may have efficacy for the
      treatment of  testosterone deficiency.

PMID- 21868747
TI  - Live birth after intrauterine insemination with spermatozoa from an
      oligoasthenozoospermic patient vitrified without permeable cryoprotectants.
AB  - We report the first case of a healthy baby born after intrauterine  insemination
      with vitrified swim-up spermatozoa from an oligoasthenozoospermic  patient. A 39
      year-old patient was subjected to intrauterine insemination with  spermatozoa
      from her 35-year-old husband, diagnosed with  oligoasthenozoospermia. The swim-up
      spermatozoa from 2 ejaculates were  suspended in a culture medium supplemented
      with 1% human serum albumin and  0.25 M sucrose. Three hermetically packaged 100
      MUL sperm portions (each  containing 1.0 * 10(6) spermatozoa/mL) were vitrified
      by direct  plunging into liquid nitrogen. The presence of leukocytes in the
      ejaculates  was determined by indirect immunofluorescence assay. Production of
      reactive  oxygen species was measured by chemiluminescent assay. Before
      intrauterine  insemination, all portions were warmed in culture medium at 37
      degrees C, and the  spermatozoa were concentrated by centrifugation; they were
      then resuspended in  500 MUL of culture medium and inseminated. The cell
      suspension used for  insemination displayed 60% progressive motility. Clinical
      pregnancy was  confirmed at 7 weeks of gestation, and a healthy baby was born at
      term. Our  results show that a successful intrauterine insemination can be
      achieved with  aseptic vitrification of spermatozoa.

PMID- 21868748
TI  - Glans-preserving surgery for superficial penile cancer.
AB  - In this study, we investigated the safety and feasibility of  glans-preserving
      surgery for superficial penile squamous cell carcinoma. Young  patients with
      penile primary tumors exhibiting favorable histologic features  were best suited
      for organ-sparing procedures, enabling them to avoid sexual  disturbances. The
      study included 12 patients, 38-53 years of age (median  age 46 years), with
      superficial lesions involving the glans penis, coronary  sulcus, or shaft skin.
      After clinical staging and grading, those patients were  offered a glans
      preserving procedure to preserve the normal appearance and  functional integrity
      of the glans penis. Of the 12 patients referred, the  tumors were TaG1 in 4
      patients, TaG2 in 3, TisG1 in 1, TisG2 in 1, T1G1 in 2,  and T1G2 in 1. All
      patients returned to normal sexual activity 1 month  postoperatively. Sexual
      function and sexual satisfaction were well maintained  after surgery. The
      cosmetic results were considered satisfying/very satisfying  by 83% (10 of 12
      patients). Follow-up data were available on 12 patients at a  mean follow-up of
      62.5 months. Only 1 patient had recurrence 6 months after  surgery, which was
      managed by a second glans-preserving surgery without  recurrence. With careful
      patient selection and vigilant follow-up,  anatomically suitable superficial
      penile cancer can be offered this  glans-preserving surgery, while preserving
      function of the penis wherever  possible.

PMID- 21868750
TI  - Inhibition of claudin-11 and occludin expression in rat Sertoli cells by mono-(2
      ethylhexyl) phthalate through p44/42 mitogen-activated protein kinase pathway.
AB  - Our objectives were to evaluate the effects of mono(2-ethylhexyl) phthalate 
      (MEHP) on tight junctions (TJ) in cultured rat Sertoli cells (SC) and to 
      investigate changes in the signal transduction pathways in SCs following MEHP 
      treatment. SCs were isolated and purified from the testes of 18-day-old  Sprague
      Dawley rats and incubated at 34 degrees C for 3 days. After treatment of  SCs
      with either the vehicle or MEHP for 0.5, 1, 3, 6 and 24 hours, whole cell 
      lysates were isolated from each replicate to prepare RNA and protein.  Expression
      levels of claudin-11, occludin, and zonula occludens-1 (ZO-1) mRNA  were
      evaluated by quantitative real-time reverse  transcription-polymerase chain
      reaction and changes in signal  transduction pathways possibly induced by MEHP
      treatment were assessed by  Western blot analyses. MEHP treatment led to
      significant decreases in the  expression of claudin-11 and occludin mRNA, but not
      that of ZO-1, in rat SCs.  Exposure of rat SCs to MEHP resulted in the marked
      induction of phosphorylated  p44/42 mitogen-activated protein kinase (MAPK),
      whereas other pathways  examined in this study were not activated by MEHP.
      Furthermore, treatment of  rat SCs with a specific inhibitor of p44/42 MAPK
      prevented the MEHP-induced  down-regulation of claudin-11 and occludin. These
      findings demonstrate that  MEHP exposure inhibited the expression of claudin-11
      and occludin mRNA in rat  SCs through the p44/42 MAPK pathway, suggesting the
      possible involvement of  MEHP in spermatogenic function by regulating major
      components of TJs in  SCs.

PMID- 21868749
TI  - Induction and persistence of abnormal testicular germ cells following gestational
      exposure to di-(n-butyl) phthalate in p53-null mice.
AB  - Phthalate esters are commonly used plasticizers found in many household  items,
      personal care products, and medical devices. Animal studies have shown  that in
      utero exposure to di-(n-butyl) phthalate (DBP) within a  critical window during
      gestation causes male reproductive tract abnormalities  resembling testicular
      dysgenesis syndrome. Our studies utilized p53-deficient  mice for their ability
      to display greater resistance to apoptosis during  development. This model was
      chosen to determine whether multinucleated germ  cells (MNG) induced by
      gestational DBP exposure could survive postnatally and  evolve into testicular
      germ cell cancer. Pregnant dams were exposed to DBP  (500 mg/kg/day) by oral
      gavage from gestational day 12 until birth. Perinatal  effects were assessed on
      gestational day 19 and postnatal days 1, 4, 7, and 10  for the number of MNGs
      present in control and DBP-treated p53-heterozygous and  null animals. As
      expected, DBP exposure induced MNGs, with greater numbers  found in p53-null
      mice. Additionally, there was a time-dependent decrease in  the incidence of MNGs
      during the early postnatal period. Histologic  examination of adult mice exposed
      in utero to DBP revealed persistence of  abnormal germ cells only in DBP-treated
      p53-null mice, not in p53-heterozygous  or wild-type mice. Immunohistochemical
      staining of perinatal MNGs and adult  abnormal germ cells was negative for both
      octamer-binding protein 3/4 and  placental alkaline phosphatase. This unique
      model identified a role for p53 in  the perinatal apoptosis of DBP-induced MNGs
      and provided insight into the  long-term effects of gestational DBP exposure
      within a p53-null  environment.

PMID- 21868751
TI  - The impact of transurethral procedures for benign prostate hyperplasia on male
      sexual function: a meta-analysis.
AB  - The effect of transurethral procedures for benign prostate hyperplasia  (BPH) on
      male sexual function is still controversial, and we conducted this  meta-analysis
      to compare the effects of different transurethral surgical  procedures for the
      treatment of symptomatic BPH on male erectile function (EF)  and ejaculatory
      function (EJF). Databases, including MEDLINE, EMBASE, and the  Cochrane
      Controlled Trial Register, were searched to identify randomized  controlled
      trials (RCT) that compared watchful waiting, transurethral  electrovaporization
      (TUEVP) or holmium laser treatment (HLT) with  transurethral resection of the
      prostate (TURP). Trials were included if they  were RCTs, contained fully
      available data, compared with conventional TURP for  BPH, and referred to male EF
      and EJF. A total of 12 RCTs involving a total of  1889 subjects were selected for
      analysis, including 2 trials comparing TURP  and watchful waiting, 6 comparing
      TURP with TUEVP, and 4 comparing TURP with  HLT. TURP was associated with a
      higher occurrence of retrograde ejaculation  compared with watchful waiting but
      not to TUEVP (P = .95) or HLT  (P = .37) and associated with a lower incidence of
      male erectile  dysfunction compared with TUEVP (P = .04) but not HLT. According
      to  the analysis, TURP lead to a higher prevalence of retrograde ejaculation 
      compared with watchful waiting but had less of an effect on EF than TUEVP.  TURP
      did not have a significantly different effect on EF or EJF compared with  HLT.

PMID- 21868752
TI  - Recombinant human FSH reduces sperm DNA fragmentation in men with idiopathic
      oligoasthenoteratozoospermia.
AB  - A prospective randomized controlled study was designed to evaluate the  effects
      of recombinant human follicle-stimulating hormone (rFSH) treatment on  sperm DNA
      fragmentation in men with idiopathic oligoasthenoteratozoospermia  (iOAT). One
      hundred twenty-nine men with sperm count less than 10 *  10(6) spermatozoa/mL and
      forward motility <25% were included;  normal serum levels of FSH, luteinizing
      hormone (LH), and testosterone, and no  other causes of infertility were
      enrolled. The patients were randomized into 2  groups: 65 men were treated on
      alternate days for 90 days with injections of  150 IU rFSH, and 64 subjects
      received nonantioxidant vitamin supplements. Main  outcome measures were serum
      levels of FSH, LH, testosterone, and inhibin B and  DNA fragmentation index (DFI)
      at baseline and after 90 days. No significant  differences were observed between
      the 2 groups with regard to sperm parameters  and hormone values. The DFI was
      similar between the 2 groups at the time of  the enrollment but reduced
      significantly (P < .05) after rFSH  therapy in study group, whereas no
      significant variation occurred in the  control group. In the subgroup of patients
      with high basal DFI values  (>15%), rFSH treatment significantly increased DFI (P
      < .01),  whereas no significant variation occurred after 90 days of vitamin 
      supplements. We conclude that rFSH administration improves sperm DNA integrity 
      in iOAT men with increased DFI values. The degree of sperm DFI might be useful 
      to identify those iOAT patients in which rFSH treatment can be  advantageous.

PMID- 21868753
TI  - Combined tadalafil and alpha-blocker therapy for benign prostatic hyperplasia in
      patients with erectile dysfunction: a multicenter, prospective study.
AB  - This prospective study evaluated the safety of tadalafil 5 mg taken once a  day
      in terms of hypotensive side effects and whether it improves lower urinary  tract
      symptoms (LUTS) and restores sexual function in patients with erectile 
      dysfunction who are receiving concomitant alpha-blocker (AB) therapy for  benign
      prostatic hyperplasia (BPH). A total of 158 LUTS/BPH patients receiving  AB
      therapy for >=3 months were given tadalafil 5 mg once a day. Before  treatment
      with tadalafil (V1), and 4 weeks (V2) and 12 weeks (V3) after  starting
      tadalafil, blood pressure, heart rate, International Prostate Symptom  Score
      (IPSS), maximal urine flow rate (Qmax), postvoiding residual urine  volume, and
      International Index of Erectile Function (IIEF-5) score were  measured. Of the
      158 LUTS/BPH patients, a total of 119 completed the trial.  Blood pressure
      (systolic and diastolic) and heart rate did not change. IPSS  and IIEF-5 scores
      improved significantly, but Qmax and postvoiding residual  urine volume did not;
      however, in the 39 men with a low baseline Qmax (<=10  mL/s), Qmax rose
      significantly from 7.97 +/- 1.44 mL/s (baseline) to 8.91  +/- 1.60 mL/s (V3; P =
      .012). The remaining patients (baseline  Qmax >10 mL/s) did not change. At V2 and
      V3, adverse side effects were  observed in 10 men (7.30%) and 6 men (5.04%),
      respectively. Facial flushing  was the most common adverse side effect (6 men at
      V2 and 4 men at V3),  followed by headache (2 men each at V2 and V3) and
      dizziness (2 men at V2).  Two patients dropped out of the study because of
      adverse side effects. In  conclusion, tadalafil 5 mg once a day in combination
      with AB appeared to have  few adverse effects on hypotensive events and can
      improve LUTS and restore  sexual function.

PMID- 21868754
TI  - miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation
      in endometrial cancer.
AB  - The etiology and development of human cancers that remain little understood might
      be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study,
      we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial
      cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer
      cell proliferation assay identified 103 miRNAs that inhibited cell growth. We
      then determined the sequence, DNA methylation status, and expression levels of
      these miRNAs in endometrial cancer cell lines and primary tumors. These
      determinations led to the identification of miR-152 as a candidate TS-miRNA gene
      in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent
      with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also
      silenced often in endometrial cancer by DNA hypermethylation, and also with
      evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably,
      restoration of miR-152 expression in endometrial cancer cell lines was sufficient
      to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and
      Rictor as novel candidate targets of miR-152, suggesting how its epigenetic
      silencing can drive endometrial carcinogenesis. Our findings define a central
      role for miR-152 in endometrial cancer, and they also suggest its use in new
      therapeutic strategies to treat this cancer.

PMID- 21868755
TI  - Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3.
AB  - Celecoxib is a COX-2 inhibitor that reduces the risk of colon cancer. However,
      the basis for its cancer chemopreventive activity is not fully understood. In
      this study, we defined a mechanism of celecoxib action based on degradation of
      cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death
      receptor pathway of apoptosis. c-FLIP protein levels are regulated by
      ubiquitination and proteasome-mediated degradation. We found that celecoxib
      controlled c-FLIP ubiquitination through Akt-independent inhibition of glycogen
      synthase kinase-3 (GSK3), itself a candidate therapeutic target of interest in
      colon cancer. Celecoxib increased the levels of phosphorylated GSK3, including
      the alpha and beta forms, even in cell lines, where phosphorylated Akt levels
      were not increased. Phosphoinositide 3-kinase inhibitors abrogated Akt
      phosphorylation as expected but had no effect on celecoxib-induced GSK3
      phosphorylation. In contrast, protein kinase C (PKC) inhibitors abolished
      celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3
      phosphorylation through a mechanism that relied upon PKC and not Akt. GSK3
      blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP
      levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP
      and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3
      inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP
      attenuation was mediated by proteasomal turnover as expected. Our findings reveal
      a novel mechanism through which the regulatory effects of c-FLIP on death
      receptor signaling are controlled by GSK3, which celecoxib acts at an upstream
      level to control independently of Akt.

PMID- 21868756
TI  - Activation of the glucocorticoid receptor is associated with poor prognosis in
      estrogen receptor-negative breast cancer.
AB  - Estrogen receptor-negative (ER(-)) breast cancers have limited treatment options
      and are associated with earlier relapses. Because glucocorticoid receptor (GR)
      signaling initiates antiapoptotic pathways in ER(-) breast cancer cells, we
      hypothesized that activation of these pathways might be associated with poor
      prognosis in ER(-) disease. Here we report findings from a genome-wide study of
      GR transcriptional targets in a premalignant ER(-) cell line model of early
      breast cancer (MCF10A-Myc) and in primary early-stage ER(-) human tumors.
      Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq)
      coupled to time-course expression profiling led us to identify epithelial-to
      mesenchymal transition (EMT) pathways as an important aspect associated with GR
      activation. We validated these findings by carrying out a meta-analysis of
      primary breast tumor gene expression from 1,378 early-stage breast cancer
      patients with long-term clinical follow-up, confirming that high levels of GR
      expression significantly correlated with shorter relapse-free survival in ER(-)
      patients who were treated or untreated with adjuvant chemotherapy. Notably, in
      ER(+) breast cancer patients, high levels of GR expression in tumors were
      significantly associated with better outcome relative to low levels of GR
      expression. Gene expression analysis revealed that ER(-) tumors expressing high
      GR levels exhibited differential activation of EMT, cell adhesion, and
      inflammation pathways. Our findings suggest a direct transcriptional role for GR
      in determining the outcome of poor-prognosis ER(-) breast cancers.

PMID- 21868757
TI  - Asialoglycoprotein receptor promotes cancer metastasis by activating the EGFR-ERK
      pathway.
AB  - Although the importance of glycans in malignant cell behavior is well documented,
      the potential involvement of endogenous lectins as modifiers of progression and
      metastasis in the tumor microenvironment has not been explored. In this study, we
      show that loss of the hepatic asialoglycoprotein receptor (ASGPR) in mice
      severely reduces the frequency of spontaneous lung metastasis after intrahepatic
      implantation of murine Lewis lung carcinoma (3LL) cells. Conversely, in vitro
      treatment with recombinant ASGPR increased the invasive and metastatic capacity
      of 3LL cells before intrahepatic implantation. ASGPR treatment in vitro increased
      the expression and production of matrix metalloproteinase-9 through activation of
      the epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR
      ERK) pathway. Our findings identify ASGPR as a novel important factor that
      responds to endogenous lectins in the tumor microenvironment to promote cancer
      metastasis by activating the EGFR-ERK pathway through interactions with counter
      receptors on cancer cells.

PMID- 21868759
TI  - A role for bone morphogenetic protein-4 in lymph node vascular remodeling and
      primary tumor growth.
AB  - Lymph node metastasis, an early and prognostically important event in the
      progression of many human cancers, is associated with expression of VEGF-D.
      Changes to lymph node vasculature that occur during malignant progression may
      create a metastatic niche capable of attracting and supporting tumor cells. In
      this study, we sought to characterize molecules expressed in lymph node
      endothelium that could represent therapeutic or prognostic targets. Differential
      mRNA expression profiling of endothelial cells from lymph nodes that drained
      metastatic or nonmetastatic primary tumors revealed genes associated with tumor
      progression, in particular bone morphogenetic protein-4 (BMP-4). Metastasis
      driven by VEGF-D was associated with reduced BMP-4 expression in high endothelial
      venules, where BMP-4 loss could remodel the typical high-walled phenotype to thin
      walled vessels. VEGF-D expression was sufficient to suppress proliferation of the
      more typical BMP-4-expressing high endothelial venules in favor of remodeled
      vessels, and mechanistic studies indicated that VEGF receptor-2 contributed to
      high endothelial venule proliferation and remodeling. BMP-4 could regulate high
      endothelial venule phenotype and cellular function, thereby determining
      morphology and proliferation responses. Notably, therapeutic administration of
      BMP-4 suppressed primary tumor growth, acting both at the level of tumor cells
      and tumor stromal cells. Together, our results show that VEGF-D-driven metastasis
      induces vascular remodeling in lymph nodes. Furthermore, they implicate BMP-4 as
      a negative regulator of this process, suggesting its potential utility as a
      prognostic marker or antitumor agent.

PMID- 21868758
TI  - Intratumoral de novo steroid synthesis activates androgen receptor in castration
      resistant prostate cancer and is upregulated by treatment with CYP17A1
      inhibitors.
AB  - Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen
      deprivation therapy of primary prostate cancer can be mediated by reactivation of
      the androgen receptor (AR). One important mechanism mediating this AR
      reactivation is intratumoral conversion of the weak adrenal androgens DHEA and
      androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA
      and androstenedione are synthesized by the adrenals through the sequential
      actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1
      inhibitors such as abiraterone are effective therapies for CRPC. However, the
      significance of intratumoral CYP17A1 and de novo androgen synthesis from
      cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor
      resistance/relapse, remain to be determined. We report that AR activity in
      castration-resistant VCaP tumor xenografts can be restored through CYP17A1
      dependent de novo androgen synthesis, and that abiraterone treatment of these
      xenografts imposes selective pressure for increased intratumoral expression of
      CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1
      inhibitors. Supporting the clinical relevance of this mechanism, we found that
      intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from
      CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells
      expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent,
      but that AR activity in these cells is still steroid dependent and mediated by
      upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis.
      Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may
      remain steroid dependent and therefore responsive to therapies that can further
      suppress de novo intratumoral steroid synthesis.

PMID- 21868760
TI  - Pivotal role of reduced let-7g expression in breast cancer invasion and
      metastasis.
AB  - Screening of the entire let-7 family of microRNAs (miRNA) by in situ
      hybridization identified let-7g as the only member, the diminished expression of
      which was significantly associated with lymph node metastasis and poor survival
      in breast cancer patients. Abrogation of let-7g expression in otherwise
      nonmetastatic mammary carcinoma cells elicited rapid metastasis from the
      orthotopic location, through preferential targets, Grb2-associated binding
      protein 2 (GAB2) and fibronectin 1 (FN1), and consequent activation of p44/42
      mitogen-activated protein kinase (MAPK) and specific matrix metalloproteinases.
      Treatment with estrogen or epidermal growth factor specifically reduced the
      expression of mature let-7g through activation of p44/42 MAPK and subsequently
      stimulated expression of GAB2 and FN1, which, in turn, promoted tumor invasion.
      We thus identify let-7g as a unique member of the let-7 miRNA family that can
      serve as a prognostic biomarker in breast cancer and also propose a paradigm used
      by specific signaling molecules via let-7g to cooperatively promote breast cancer
      invasion and metastasis. Thus, let-7 family members neither possess equivalent
      clinicopathologic correlation nor function in breast cancer.

PMID- 21868761
TI  - Loss of transcription factor KLF5 in the context of p53 ablation drives invasive
      progression of human squamous cell cancer.
AB  - Squamous cell cancers account for more than half of all human cancers, and
      esophageal cancer is the sixth leading cause of cancer death worldwide. The
      majority of esophageal squamous cell carcinomas have identifiable p53 mutations,
      yet the same p53 mutations are found at comparable frequencies in precancerous
      dysplasia, indicating that transformation requires additional somatic changes yet
      to be defined. Here, we show that the zinc finger transcription factor Kruppel
      like factor 5 (KLF5) transactivates NOTCH1 in the context of p53 mutation or
      loss. KLF5 loss limited NOTCH1 activity and was sufficient on its own to
      transform primary human keratinocytes harboring mutant p53, leading to the
      formation of invasive tumors. Restoration of NOTCH1 blocked transformation of
      KLF5-deficient and p53-mutant keratinocytes. Although human dysplastic epithelia
      accumulated KLF5, KLF5 expression was lost concurrently with NOTCH1 in squamous
      cell cancers. Taken together, these results define KLF5 loss as a critical event
      in squamous cell transformation and invasion. Our findings suggest that KLF5 may
      be a useful diagnostic and therapeutic target in esophageal squamous carcinomas
      and possibly more generally in other cancers associated with p53 loss of
      function.

PMID- 21868762
TI  - MALT1 protease: a new therapeutic target in B lymphoma and beyond?
AB  - The identification of mucosa-associated lymphoid tissue lymphoma translocation 1
      (MALT1) as a gene that is perturbed in the B-cell neoplasm MALT lymphoma, already
      more than a decade ago, was the starting point for an intense area of research.
      The fascination with MALT1 was fueled further by the observation that it contains
      a domain homologous to the catalytic domain of caspases and thus, potentially,
      could function as a protease. Discoveries since then initially revealed that
      MALT1 is a key adaptor molecule in antigen receptor signaling to the
      transcription factor NF-kappaB, which is crucial for lymphocyte function.
      However, recent discoveries show that this function of MALT1 is not restricted to
      lymphocytes, witnessed by the ever-increasing list of receptors from cells within
      and outside of the immune system that require MALT1 for NF-kappaB activation.
      Yet, a role for MALT1 protease activity was shown only recently in immune
      signaling, and its importance was then further strengthened by the dependency of
      NF-kappaB-addicted B-cell lymphomas on this proteolytic activity. Therapeutic
      targeting of MALT1 protease activity might, therefore, become a useful approach
      for the treatment of these lymphomas and, additionally, an effective strategy for
      treating other neoplastic and inflammatory disorders associated with deregulated
      NF-kappaB signaling.

PMID- 21868764
TI  - Assembly and initial characterization of a panel of 85 genomically validated cell
      lines from diverse head and neck tumor sites.
AB  - PURPOSE: Human cell lines are useful for studying cancer biology and
      preclinically modeling cancer therapy, but can be misidentified and cross
      contamination is unfortunately common. The purpose of this study was to develop a
      panel of validated head and neck cell lines representing the spectrum of tissue
      sites and histologies that could be used for studying the molecular, genetic, and
      phenotypic diversity of head and neck cancer. METHODS: A panel of 122 clinically
      and phenotypically diverse head and neck cell lines from head and neck squamous
      cell carcinoma, thyroid cancer, cutaneous squamous cell carcinoma, adenoid cystic
      carcinoma, oral leukoplakia, immortalized primary keratinocytes, and normal
      epithelium was assembled from the collections of several individuals and
      institutions. Authenticity was verified by carrying out short tandem repeat
      analysis. Human papillomavirus (HPV) status and cell morphology were also
      determined. RESULTS: Eighty-five of the 122 cell lines had unique genetic
      profiles. HPV-16 DNA was detected in 2 cell lines. These 85 cell lines included
      cell lines from the major head and neck primary tumor sites, and close
      examination shows a wide range of in vitro phenotypes. CONCLUSIONS: This panel of
      85 genomically validated head and neck cell lines represents a valuable resource
      for the head and neck cancer research community that can help advance
      understanding of the disease by providing a standard reference for cell lines
      that can be used for biological as well as preclinical studies.

PMID- 21868763
TI  - Polymeric nanoparticle-encapsulated hedgehog pathway inhibitor HPI-1 (NanoHHI)
      inhibits systemic metastases in an orthotopic model of human hepatocellular
      carcinoma.
AB  - PURPOSE: To illustrate the prognostic significance of hedgehog (Hh) signaling in
      patients with hepatocellular carcinoma (HCC) and to evaluate the efficacy of a
      novel nanoparticle-encapsulated inhibitor of the Hh transcription factor, Gli1
      (NanoHHI) using in vitro and in vivo models of human HCCs. EXPERIMENTAL DESIGN:
      Patched1 (Ptch1) expression was detected in tumor tissue microarrays of 396
      patients with HCC who underwent curative surgical resection during February 2000
      to December 2002. Prognostic significance was assessed using Kaplan-Meier
      survival estimates and log-rank tests. The effects of NanoHHI alone and in
      combination with sorafenib were investigated on HCC cell lines. Primary HCC tumor
      growth and metastasis were examined in vivo using subcutaneous and orthotopic HCC
      xenografts in nude mice. RESULTS: Elevated expression of Ptch1 in HCC tissues was
      significantly related to disease recurrence, as well as a shorter time to
      recurrence in patients with HCC. In vitro, NanoHHI significantly inhibited the
      proliferation and invasion of HCC cell lines. NanoHHI potently suppressed in vivo
      tumor growth of HCC xenografts in both subcutaneous and orthotopic milieus, and
      in contrast to sorafenib, resulted in significant attenuation of systemic
      metastases in the orthotopic setting. Furthermore, NanoHHI significantly
      decreased the population of CD133-expressing HCC cells, which have been
      implicated in tumor initiation and metastases. CONCLUSION: Downstream Hh
      signaling has prognostic significance in patients with HCC as it predicts early
      recurrence. Gli inhibition through NanoHHI has profound tumor growth inhibition
      and antimetastatic effects in HCC models, which may provide a new strategy in the
      treatment of patients with HCC and prevention post-operative recurrence.

PMID- 21868765
TI  - Discriminant analysis of 18F-fluorothymidine kinetic parameters to predict
      survival in patients with recurrent high-grade glioma.
AB  - PURPOSE: The primary objective of this study was to investigate whether changes
      in 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) kinetic parameters, taken early
      after the start of therapy, could predict overall survival (OS) and progression
      free survival (PFS) in patients with recurrent malignant glioma undergoing
      treatment with bevacizumab and irinotecan. EXPERIMENTAL DESIGN: High-grade
      recurrent brain tumors were investigated in 18 patients (8 male and 10 female),
      ages 26 to 76 years. Each had 3 dynamic positron emission tomography (PET)
      studies as follows: at baseline and after 2 and 6 weeks from the start of
      treatment, 18F-FLT (2.0 MBq/kg) was injected intravenously, and dynamic PET
      images were acquired for 1 hour. Factor analysis generated factor images from
      which blood and tumor uptake curves were derived. A three-compartment, two-tissue
      model was applied to estimate tumor 18F-FLT kinetic rate constants using a
      metabolite- and partial volume-corrected input function. Different combinations
      of predictor variables were exhaustively searched in a discriminant function to
      accurately classify patients into their known OS and PFS groups. A leave-one-out
      cross-validation technique was used to assess the generalizability of the model
      predictions. RESULTS: In this study population, changes in single parameters such
      as standardized uptake value or influx rate constant did not accurately classify
      patients into their respective OS groups (<1 and >= 1 year; hit ratios <= 78%).
      However, changes in a set of 18F-FLT kinetic parameters could perfectly separate
      these two groups of patients (hit ratio = 100%) and were also able to correctly
      classify patients into their respective PFS groups (<100 and >= 100 days; hit
      ratio = 88%). CONCLUSIONS: Discriminant analysis using changes in 18F-FLT kinetic
      parameters early during treatment seems to be a powerful method for evaluating
      the efficacy of therapeutic regimens.

PMID- 21868766
TI  - Prevention of chemotherapy-induced anemia and thrombocytopenia by constant
      administration of stem cell factor.
AB  - PURPOSE: Chemotherapy-induced apoptosis of immature hematopoietic cells is a
      major cause of anemia and thrombocytopenia in cancer patients. Although
      hematopoietic growth factors such as erythropoietin and colony-stimulating
      factors cannot prevent the occurrence of drug-induced myelosuppression, stem cell
      factor (SCF) has been previously shown to protect immature erythroid and
      megakaryocytic cells in vitro from drug-induced apoptosis. However, the effect of
      SCF in vivo as a single myeloprotective agent has never been elucidated.
      EXPERIMENTAL DESIGN: The ability of SCF to prevent the occurrence of chemotherapy
      induced anemia and thrombocytopenia was tested in a mouse model of cisplatin
      induced myelosuppression. To highlight the importance of maintaining a continuous
      antiapoptotic signal in immature hematopoietic cells, we compared two treatment
      schedules: in the first schedule, SCF administration was interrupted during
      chemotherapy treatment and resumed thereafter, whereas in the second schedule,
      SCF was administered without interruption for 7 days, including the day of
      chemotherapy treatment. RESULTS: The administration of SCF to cisplatin-treated
      mice could preserve bone marrow integrity, inhibit apoptosis of erythroid and
      megakaryocytic precursors, prevent chemotherapy-induced anemia, and rapidly
      restore normal platelet production. Treatment with SCF increased the frequency of
      Bcl-2/Bcl-XL-positive bone marrow erythroid cells and sustained Akt activation in
      megakaryocytes. Myeloprotection was observed only when SCF was administered
      concomitantly with cisplatin and kept constantly present during the days
      following chemotherapy treatment. CONCLUSIONS: SCF treatment can prevent the
      occurrence of chemotherapy-induced anemia and thrombocytopenia in mice,
      indicating a potential use of this cytokine in the supportive therapy of cancer
      patients.

PMID- 21868767
TI  - Preclinical 28-day inhalation toxicity assessment of s-nitrosoglutathione in
      beagle dogs and Wistar rats.
AB  - To support clinical development of S-nitrosoglutathione (GSNO) as a therapeutic
      agent, 28-day toxicology studies in rats and dogs were conducted. Rats (21
      25/sex) and dogs (3-5/sex) were exposed for 4 hours or 1 hour, respectively, to
      inhaled GSNO (0, 3, 9.3, 19, and 28 mg/kg per d in rats and 0, 4.6, 9.0, and 16.2
      mg/kg per d in dogs) or vehicle daily via a nebulizer. Animals were monitored
      throughout the 28-day dosing period and during a postexposure recovery period.
      Complete necropsy and tissue examinations were performed. Experimental end points
      included clinical pathology, toxicokinetics, and immunotoxicology. No
      biologically significant adverse findings were noted in either species, and the
      no observed adverse effect levels (NOAELs) under these conditions were the
      highest achieved doses (28 and 16.2 mg/kg per d in rats and dogs, respectively).
      These data demonstrate that GSNO is well tolerated in rodents and dogs and
      predict a favorable toxicity profile in humans, thus supporting future clinical
      development of GSNO or closely related compounds.

PMID- 21868768
TI  - Drug design structural alert: formation of trifluoroacetaldehyde through N
      dealkylation is linked to testicular lesions in rat.
AB  - In the process of drug design, it is important to consider potential structural
      alerts that may lead to toxicosis. This work illustrates how using
      trifluoroethane as a part of a novel chemical entity led to cytochrome P450 -
      mediated N-dealkylation and the formation of trifluoroacetaldehyde, a known
      testicular toxicant, in exploratory safety studies in rats. Testicular toxicosis
      was noted microscopically in a dose-dependent manner as measured by testicular
      spermatocytic degeneration and necrosis and excessive intratubular cellular
      debris in the epididymis. This apparent toxic effect correlated well with the
      dose-dependent formation of trifluoroacetaldehyde, identified from in vitro rat
      liver microsome metabolism studies. A similar safety study performed with an N
      tetrazole substitution in place of the N-trifluoroethane showed no evidence of
      testicular injury, implicating further the role of trifluoroacetaldehyde in the
      testicular lesion observed. These results highlight the relevance of early
      metabolic and safety testing in assessing potential structural alerts in drug
      design.

PMID- 21868769
TI  - World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease: part
      3.

PMID- 21868770
TI  - Insulin autoimmune syndrome induced by alpha-lipoic acid in a Caucasian woman:
      case report.

PMID- 21868771
TI  - Vitamin K2 supplementation improves insulin sensitivity via osteocalcin
      metabolism: a placebo-controlled trial.

PMID- 21868772
TI  - Comment on: Sun et al. Protection from retinopathy and other complications in
      patients with type 1 diabetes of extreme duration: the Joslin 50-Year Medalist
      Study. Diabetes Care 2011;34:968-974.

PMID- 21868774
TI  - Comment on: Gaillard et al. HDL dysfunctionality (paraoxonase) is worse in
      nondiabetic, postmenopausal african american than in white women. Diabetes Care
      2011;34:e19.

PMID- 21868776
TI  - Household income and cardiovascular disease risks in U.S. children and young
      adults: analyses from NHANES 1999-2008.
AB  - OBJECTIVE: To assess the cardiovascular risk profile of youths across
      socioeconomic groups in the U.S. RESEARCH DESIGN AND METHODS: Analysis of 1999
      2008 National Health and Nutrition Examination Surveys (NHANES) including 16,085
      nonpregnant 6- to 24-year-olds to estimate race/ethnicity-adjusted prevalence of
      obesity, central obesity, sedentary behaviors, tobacco exposure, elevated
      systolic blood pressure, glycated hemoglobin, non-HDL cholesterol (non-HDL-C),
      and high-sensitivity C-reactive protein according to age-group, sex, and poverty
      income ratio (PIR) tertiles. RESULTS: Among boys aged 6-11 years, 19.9% in the
      lowest PIR tertile were obese and 30.0% were centrally obese compared with 13.2
      and 21.6%, respectively, in the highest-income tertile households (P(obesity) <
      0.05 and P(central obesity) < 0.01). Boys aged 12-17 years in lowest-income
      households were more likely than their wealthiest family peers to be obese (20.6
      vs. 15.6%, P < 0.05), sedentary (14.8 vs. 9.3%, P < 0.05), and exposed to tobacco
      (19.0 vs. 6.5%, P < 0.01). Compared with girls aged 12-17 years in highest-income
      households, lowest-income household girls had higher prevalence of obesity (17.9
      vs. 13.1%, P < 0.05), central obesity (41.5 vs. 29.2%, P < 0.01), sedentary
      behaviors (20.4 vs. 9.4%, P < 0.01), and tobacco exposure (14.1 vs. 5.9%, P <
      0.01). Apart from higher prevalence of elevated non-HDL-C among low-income women
      aged 18-24 years (23.4 vs. 15.8%, P < 0.05), no other cardiovascular disease risk
      factor prevalence differences were observed between lowest- and highest-income
      background young adults. CONCLUSIONS: Independent of race/ethnicity, 6- to 17
      year-olds from low-income families have higher prevalence of obesity, central
      obesity, sedentary behavior, and tobacco exposure. Multifaceted cardiovascular
      health promotion policies are needed to reduce health disparities between income
      groups.

PMID- 21868777
TI  - Decline in the cumulative incidence of severe diabetic retinopathy in patients
      with type 1 diabetes.
AB  - OBJECTIVE: To determine if the cumulative incidence of severe retinopathy in
      patients with type 1 diabetes has changed. RESEARCH DESIGN AND METHODS: The study
      looked at 3,781 patients diagnosed with type 1 diabetes (1939-2005), median age
      at onset 13 (interquartile range [IQR] 9-21) years, and duration of diabetes 19
      (IQR 13-27) years. The severe retinopathy was based on a history of laser
      treatment. Patients were divided into <1975, 1975-1979, 1980-1984, and >=1985
      cohorts according to the diagnosis of diabetes. RESULTS: The cumulative incidence
      of severe retinopathy has declined (P < 0.0001). After 20 years of duration, the
      cumulative incidence was 23% (95% CI 21-25) and 33 (30-35) in the earliest
      cohorts, 18 (15-21) in the next cohort, and 6 (4-9) in the recent cohort. After
      30 years, the cumulative incidence was 52 and 48% in the earliest cohorts, while
      it was 62% after 40 years in the earliest cohort. CONCLUSIONS: The cumulative
      incidence of severe retinopathy has declined in patients with type 1 diabetes.

PMID- 21868778
TI  - Insulin pump therapy with automated insulin suspension in response to
      hypoglycemia: reduction in nocturnal hypoglycemia in those at greatest risk.
AB  - OBJECTIVE: To evaluate a sensor-augmented insulin pump with a low glucose suspend
      (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in
      response to sensor-detected hypoglycemia. RESEARCH DESIGN AND METHODS: The LGS
      feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was
      tested for 3 weeks in 31 adults with type 1 diabetes. RESULTS: There were 166
      episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and
      20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal
      duration <=2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia
      at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median
      sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal
      restart. CONCLUSIONS: Use of an insulin pump with LGS was associated with reduced
      nocturnal hypoglycemia in those at greatest risk and was well accepted by
      patients.

PMID- 21868779
TI  - Effects of exenatide on measures of beta-cell function after 3 years in metformin
      treated patients with type 2 diabetes.
AB  - OBJECTIVE: We previously showed that exenatide (EXE) enhanced insulin secretion
      after 1 year of treatment, relative to insulin glargine (GLAR), with a similar
      glucose-lowering action. These effects were not sustained after a 4-week off-drug
      period. This article reports the results after additional 2 years of exposure.
      RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2
      diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year
      extension study in which they continued their allocated therapy. Thirty-six
      completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin
      sensitivity (M value) and beta-cell function were measured by euglycemic
      hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation
      at pretreatment (week 52) and 4 weeks after discontinuation of study medication
      (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was
      adjusted for M value and calculated as the disposition index (DI). RESULTS: At 3
      years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 +/- 0.2%
      and 6.9 +/- 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly
      reduced body weight (-7.9 +/- 1.8 kg; P < 0.001). After the 4-week off-drug
      period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P
      = 0.647). Following the 4-week off-drug period, the DI, compared with
      pretreatment, increased with EXE, but decreased with GLAR (1.43 +/- 0.78 and 
      0.99 +/- 0.65, respectively; P = 0.028). CONCLUSIONS: EXE and GLAR sustained
      HbA(1c) over the 3-year treatment period, while EXE reduced body weight and GLAR
      increased body weight. Following the 3-year treatment with EXE, the DI was
      sustained after a 4-week off-drug period. These findings suggest a beneficial
      effect on beta-cell health.

PMID- 21868780
TI  - Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort
      studies.
AB  - OBJECTIVE: Emerging epidemiological evidence suggests that higher magnesium
      intake may reduce diabetes incidence. We aimed to examine the association between
      magnesium intake and risk of type 2 diabetes by conducting a meta-analysis of
      prospective cohort studies. RESEARCH DESIGN AND METHODS: We conducted a PubMed
      database search through January 2011 to identify prospective cohort studies of
      magnesium intake and risk of type 2 diabetes. Reference lists of retrieved
      articles were also reviewed. A random-effects model was used to compute the
      summary risk estimates. RESULTS: Meta-analysis of 13 prospective cohort studies
      involving 536,318 participants and 24,516 cases detected a significant inverse
      association between magnesium intake and risk of type 2 diabetes (relative risk
      [RR] 0.78 [95% CI 0.73-0.84]). This association was not substantially modified by
      geographic region, follow-up length, sex, or family history of type 2 diabetes. A
      significant inverse association was observed in overweight (BMI >=25 kg/m(2)) but
      not in normal-weight individuals (BMI <25 kg/m(2)), although test for interaction
      was not statistically significant (P(interaction) = 0.13). In the dose-response
      analysis, the summary RR of type 2 diabetes for every 100 mg/day increment in
      magnesium intake was 0.86 (95% CI 0.82-0.89). Sensitivity analyses restricted to
      studies with adjustment for cereal fiber intake yielded similar results. Little
      evidence of publication bias was observed. CONCLUSIONS: This meta-analysis
      provides further evidence supporting that magnesium intake is significantly
      inversely associated with risk of type 2 diabetes in a dose-response manner.

PMID- 21868781
TI  - The Charcot foot in diabetes.
AB  - The diabetic Charcot foot syndrome is a serious and potentially limb-threatening
      lower-extremity complication of diabetes. First described in 1883, this enigmatic
      condition continues to challenge even the most experienced practitioners. Now
      considered an inflammatory syndrome, the diabetic Charcot foot is characterized
      by varying degrees of bone and joint disorganization secondary to underlying
      neuropathy, trauma, and perturbations of bone metabolism. An international task
      force of experts was convened by the American Diabetes Association and the
      American Podiatric Medical Association in January 2011 to summarize available
      evidence on the pathophysiology, natural history, presentations, and treatment
      recommendations for this entity.

PMID- 21868782
TI  - Time for a victory lap or time to raise the levees: a perspective on complication
      reduction and new-onset diabetes.

PMID- 21868783
TI  - Incretin-based therapy and the quest for sustained improvements in beta-cell
      health.

PMID- 21868784
TI  - Closing the loop: another step forward.

PMID- 21868785
TI  - Withdrawn. Glycemic response to ingested Dreamfields pasta compared with
      traditional pasta.

PMID- 21868787
TI  - Comment on: Hoeg et al. Lipid-induced insulin resistance affects women less than
      men and is not accompanied by inflammation or impaired proximal insulin
      signaling. Diabetes 2011;60:64-73.

PMID- 21868789
TI  - Comment on: Berhan. Thirty years of prospective nationwide incidence of childhood
      type 1 diabetes: the accelerating increase by time tends to level off in Sweden.
      Diabetes 2011;60:577-581.

PMID- 21868790
TI  - Postprandial insulin secretion after gastric bypass surgery: the role of glucagon
      like peptide 1.

PMID- 21868793
TI  - A global conversation.

PMID- 21868791
TI  - Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial
      insulin secretion in humans.
AB  - OBJECTIVE: Gastric bypass (GB) surgery is associated with postprandial
      hyperinsulinemia, and this effect is accentuated in postsurgical patients who
      develop recurrent hypoglycemia. Plasma levels of the incretin glucagon-like
      peptide 1 (GLP-1) are dramatically increased after GB, suggesting that its action
      contributes to alteration in postprandial glucose regulation. The aim of this
      study was to establish the role of GLP-1 on insulin secretion in patients with
      GB. RESEARCH DESIGN AND METHODS: Twelve asymptomatic individuals with previous GB
      (Asym-GB), 10 matched healthy nonoperated control subjects, and 12 patients with
      recurrent hypoglycemia after GB (Hypo-GB) had pre- and postprandial hormone
      levels and insulin secretion rates (ISR) measured during a hyperglycemic clamp
      with either GLP-1 receptor blockade with exendin-(9-39) or saline. RESULTS:
      Blocking the action of GLP-1 suppressed postprandial ISR to a larger extent in
      Asym-GB individuals versus control subjects (33 +/- 4 vs.16 +/- 5%; P = 0.04). In
      Hypo-GB patients, GLP-1 accounted for 43 +/- 4% of postprandial ISR, which was
      not significantly higher than that in Asym-GB subjects (P = 0.20). Glucagon was
      suppressed similarly by hyperglycemia in all groups but rose significantly after
      the meal in surgical individuals but remained suppressed in nonsurgical subjects.
      GLP-1 receptor blockade increased postprandial glucagon in both surgical groups.
      CONCLUSIONS: Increased GLP-1-stimulated insulin secretion contributes
      significantly to hyperinsulinism in GB subjects. However, the exaggerated effect
      of GLP-1 on postprandial insulin secretion in surgical subjects is not
      significantly different in those with and without recurrent hypoglycemia.

PMID- 21868794
TI  - Efficacy of EZStep in the management of plantar fasciitis: a prospective,
      randomized study.
AB  - Plantar fasciitis is one of the most common causes of heel pain. Despite
      extensive efforts foot surgeons continue to debate the best modality of
      treatment. Analgesics, shoe inserts, stretching exercises, steroid injection,
      night splints, and extracorporeal shock wave therapy have proved effective in one
      group but fail in others. This study evaluated the efficacy of EZStep, a new foot
      brace for the management of plantar fasciitis. A total of 198 patients were
      randomized in 2 groups; group 1 (study group) received nonsteroidal anti
      inflammatory drugs (NSAIDs; 4-6 weeks) and EZStep whereas group 2 (control group)
      received either NSAID and physiotherapy alone (2A) or NSAID, physiotherapy, and
      local steroid injection (2B). None of the patients received over-the-counter
      insoles or strapping of plantar arch to avoid any bias in randomization.
      Evaluations included measurement of weight and height, visual analog scale (VAS)
      for pain, and Short-Form McGill Pain Questionnaire (SFMPQ). After 8 weeks,
      patients were reevaluated, and assessment for the VAS and SFMPQ with treatment
      outcome was performed. Patients with VAS scores <=3 were considered as excellent,
      >=4 as good, and >=7 as poor. The posttreatment evaluation showed that VAS scores
      were in the range from 2.97 +/- 1.06 to 7.64 +/- 2.9 (2A), P = .001, 95%
      confidence interval (CI) <-4.104; for 2B P = .001, CI <-2.44, and SFMPQ was 21.7
      +/- 4.5 and 69.2 +/- 5.8 (group 2A; P = .001, 95% CI <-46.44). Compared with
      group 2B the SFMPQ was 66.5 +/- 4.3 (P = .001, 95% CI <-30.720). In group 1 as
      per VAS, 86 (73.5%) were evaluated as excellent, 15 (12.8%) as good, and 16
      (13.6%) as poor. Our study shows that the regular use of EZStep with short course
      of NSAIDs (4-6 weeks) was effective in ameliorating symptoms in more than 85% of
      patients suffering from plantar fasciitis.

PMID- 21868795
TI  - Feasibility, safety, and primary efficacy of DermaStream: a novel continuously
      streaming device for chronic wounds.
AB  - Chronic wounds are associated with significant morbidity, mortality, and economic
      burden. Once a wound has settled into a senescent phase, outside factors must be
      used to convert that wound back to a more acute phase. Traditional methods, such
      as surgical debridement or biologic debridement, can cause removal of healthy
      tissue as well as pain to the patient. Enzymatic debridement has been under much
      scrutiny lately as popular drugs have been pulled by the Food and Drug
      Administration. The purpose of this study was to test feasibility, safety, and
      primary efficacy of 5 control subjects and 10 treatment subjects to the
      DermaStream system. It is a device that uses a continuously streaming infusion to
      create a stable, granular wound bed in a relatively short amount of time. The
      device provides for continuously streaming of therapeutic solutions to the wound
      while removing exudates by vacuum-assisted drainage throughout the treatment
      cycle.

PMID- 21868796
TI  - Treatment of plantar fasciitis in recreational athletes: two different
      therapeutic protocols.
AB  - Plantar fasciitis (PF) commonly causes inferior heel pain and occurs in up to 10%
      of the US population. Treatment protocols in most studies include the use of ice
      therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and stretching and
      strengthening protocols. The aim of the current study was to examine the
      effectiveness of 2 different therapeutic approaches on the treatment of PF in
      recreational athletes using the Pain and Disability Scale for the evaluation. A
      total of 38 participants with PF were randomly allocated to 2 different groups of
      19 male participants in each group. Group 1 was treated with ice, non-steroidal
      anti-inflammatory medication, and a stretching and a strengthening program. Group
      2 received the same therapeutic procedures as group 1, reinforced by acupuncture
      treatment. The primary outcomes, nominated a priori, were pain description and
      mobility-function at 1 and 2 months. Outcomes were measured with the pain scale
      for PF. The mean total score of the acupuncture group at the third measurement
      was statistically minor compared with the mean total score of the first group.
      Acupuncture should be considered as a major therapeutic instrument for the
      decrease of heel pain, combined with traditional medical approaches.

PMID- 21868797
TI  - Revision total ankle replacement: an early look at agility to INBONE.
AB  - INTRODUCTION. The role of total ankle replacement (TAR) is expanding in the
      United States. As the number of ankles implanted increases, undoubtedly the
      number of failures will increase. Several reports in the literature have dealt
      with salvage of the failed TAR through various methods. MeTHODS. A retrospective
      chart and radiographic review was performed on all patients who had conversion
      from a failed Agility TAR to an INBONE TAR at 2 centers and had been performed at
      least 12 months prior to the study. Exclusion criteria included any patient
      converted from a different type of TAR, primary TAR, patients followed less than
      12 months, and surgical approach other than the standard anterior incision.
      RESULTS. Five patients met inclusion criteria. The average age was 65.6 +/- 13.6
      years (range = 45-79 years). Complicating comorbidities were found with 4
      patients. The average follow-up was 17.2 +/- 6.6 months (range = 7-25 months).
      The cause of failure of the original Agility TAR was coronal plane deformity in 3
      patients, and 1 patient each failed from extensive heterotopic ossification or
      infection. All patients presented with pain. In 4 cases, there was component
      subsidence at the talus, tibia, or both. All patients had adjunctive procedures
      at the time of the revision, including malleolar screw placement in 4 patients
      and hindfoot arthrodesis in 2 patients. All patients had either 4 or 5 tibial
      stem components placed. During the follow-up period, 3 patients required
      additional surgery, including 2 patients classified as failures (1 transtibial
      amputation and 1 tibiotalocalcaneal arthrodesis). DISCUSSION. This salvage option
      is technically demanding. The authors caution against TAR revision by conversion
      in the place of previous infection and in ankle imbalance not amenable to
      reconstruction. In all cases the initial deformity was corrected. The early
      results, however, demonstrate high risk of early failure and positional changes.

PMID- 21868798
TI  - Biologics in foot and ankle surgery.

PMID- 21868799
TI  - Arthrodesis of the first metatarsal-phalangeal joint with titanium flexible
      intramedullary nails and dorsal static staple fixation.

PMID- 21868800
TI  - I think I have a good idea: what do I do with it?
AB  - The orthopaedic device industry is an ever changing market, often guided by
      creative surgeons who have the common goal of creating a solution to a problem.
      While being a surgeon-inventor can be both a challenging and rewarding process,
      there are several steps that the individual must follow to create intellectual
      property. This article serves as a guide to the novice surgeon-inventor; intended
      to be used as an early stage reference for those interested in taking their
      "solution to a problem" to the device industry.

PMID- 21868801
TI  - Genome sequence of the halotolerant marine bacterium Myxococcus fulvus HW-1.
AB  - Myxococcus fulvus HW-1 (ATCC BAA-855) is a halotolerant marine myxobacterium.
      This strain exhibits complex social behaviors in the presence of low
      concentrations of seawater but adopts an asocial living pattern under oceanic
      conditions. The whole genome of M. fulvus HW-1 will enable us to further
      investigate the details of its evolution.

PMID- 21868803
TI  - Complete genome sequence of the chloromethane-degrading Hyphomicrobium sp. strain
      MC1.
AB  - Hyphomicrobium sp. strain MC1 is an aerobic methylotroph originally isolated from
      industrial sewage. This prosthecate bacterium was the first strain reported to
      grow with chloromethane as the sole carbon and energy source. Its genome,
      consisting of a single 4.76-Mb chromosome, is the first for a chloromethane
      degrading bacterium to be formally reported.

PMID- 21868804
TI  - Draft genome sequence of Shewanella sp. strain HN-41, which produces arsenic
      sulfide nanotubes.
AB  - The dissimilatory metal reducing bacterium Shewanella sp. strain HN-41 was first
      reported to produce novel photoactive As-S nanotubes via reduction of As(V) and
      S(2)O(3)(2-) under anaerobic conditions. Here we report the draft genome sequence
      and annotation of strain HN-41.

PMID- 21868805
TI  - Genome sequence of Nitrosomonas sp. strain AL212, an ammonia-oxidizing bacterium
      sensitive to high levels of ammonia.
AB  - Nitrosomonas sp. strain AL212 is an obligate chemolithotrophic ammonia-oxidizing
      bacterium (AOB) that was originally isolated in 1997 by Yuichi Suwa and
      colleagues. This organism belongs to Nitrosomonas cluster 6A, which is
      characterized by sensitivity to high ammonia concentrations, higher substrate
      affinity (lower K(m)), and lower maximum growth rates than strains in
      Nitrosomonas cluster 7, which includes Nitrosomonas europaea and Nitrosomonas
      eutropha. Genome-informed studies of this ammonia-sensitive cohort of AOB are
      needed, as these bacteria are found in freshwater environments, drinking water
      supplies, wastewater treatment systems, and soils worldwide.

PMID- 21868806
TI  - Complete genome sequence of Streptomyces cattleya NRRL 8057, a producer of
      antibiotics and fluorometabolites.
AB  - Streptomyces cattleya, a producer of the antibiotics thienamycin and cephamycin
      C, is one of the rare bacteria known to synthesize fluorinated metabolites. The
      genome consists of two linear replicons. The genes involved in fluorine
      metabolism and in the biosynthesis of the antibiotic thienamycin were mapped on
      both replicons.

PMID- 21868802
TI  - Draft genome sequence of Lactobacillus zeae KCTC 3804.
AB  - We announce the draft genome sequence of the type strain Lactobacillus zeae KCTC
      3804 (3,110,326 bp, with a G+C content of 47.8%), which is one of the most
      prevalent lactic acid bacteria present during the processing of raw cow's milk.
      The genome consists of 113 large contigs (>100 bp). All of the contigs were
      assembled by Newbler Assembler 2.3 (454 Life Science).

PMID- 21868808
TI  - Anaemia in old and very old age: to be or not to be, that is not the question
      anymore.

PMID- 21868809
TI  - Anaemia in older persons.
AB  - Anaemia is common in older individuals and, because of its association with
      various negative outcomes, adequate diagnosis and treatment is important. The
      present review focuses on prominent factors included in diagnostic and
      therapeutic algorithms for anaemia. Although pernicious anaemia is associated
      with severe vitamin B12 deficiency, evidence of an association between subnormal
      vitamin B12 and anaemia in older persons in the general population is limited and
      inconclusive. Accumulating evidence suggests that clinicians should at least
      reconsider the risks of a low vitamin B12 level before starting vitamin B12
      supplementation in older individuals. Although clinicians may be reluctant to
      measure ferritin in older individuals due to its acute phase properties, such
      measurements are important in older persons with anaemia, especially in those
      with signs of inflammation. While a severe age-related decline in renal function
      may lead to a blunted erythropoietin response and anaemia, elevated
      erythropoietin levels are associated with increased mortality. More studies are
      needed to identify the clinical relevance and therapeutic implications of low and
      high erythropoietin levels in older persons. In contrast to other age-related
      diseases, telomere length is not associated with anaemia in older individuals in
      the general population. In conclusion, many issues regarding the aetiology of
      anaemia in old age remain unresolved. Because current guidelines on anaemia are
      based on the classic notions of the aetiology of anaemia, they may need to be
      revised for the highest age groups.

PMID- 21868810
TI  - Periprocedural reversal and bridging of anticoagulant treatment.
AB  - Anticoagulants are effective agents in reducing the risk of thromboembolism but
      the most important adverse effect of these agents is the occurrence of bleeding.
      Bleeding complications may occur spontaneously but the risk of bleeding is
      particularly increased in case of trauma or around invasive procedures. If
      patients being treated with anticoagulants need to undergo an invasive
      intervention, physicians need to consider whether to interrupt the use of this
      medication or to allow its use to be continued. Suspending the use of
      anticoagulants increases the risk of thrombosis, whereas continued use may cause
      bleeding complications. To shorten the period in which anticoagulant treatment is
      interrupted, bridging strategies have been advocated. No evidence-based
      scientific research has been carried out regarding best practice for the
      perioperative use of anticoagulants. The periprocedural anticoagulation policy in
      patients should be individualised based on the risk of a thromboembolic
      complication (which can be estimated with available scoring systems) offset
      against the bleeding risk associated with the intervention.

PMID- 21868811
TI  - Implementation of uterine artery embolisation for symptomatic uterine fibroids:
      an inventory.
AB  - The validity of uterine artery embolisation (UAE ) as an alternative treatment
      for hysterectomy to treat symptomatic uterine fibroids has been well established.
      Despite its favourable outcomes, UAE is still only marginally applied in the
      Netherlands. The aim of this inventory is to identify factors which either
      restrict or facilitate the implementation of UAE. Gynaecologists and
      interventional-radiologists in three hospitals in Amsterdam were interviewed by
      means of questionnaires. One of these hospitals had ample experience in UAE for
      uterine fibroids, one hospital had just started providing this treatment, and one
      hospital did not perform UAE. Also patients with symptomatic fibroids who were
      scheduled for either UAE or hysterectomy were interviewed about the counselling
      for UAE. The following obstacles in the implementation of UAE were found: lack of
      knowledge about UAE , absence of a multidisciplinary protocol, and above all, the
      absence of UAE as one of the treatment options in the Dutch national guideline on
      the management of menorrhagia. 75% of all patients claimed to be well informed
      about UAE by their gynaecologist. Our recommendations for the implementation of
      UAE are: 1) adding UAE to the Dutch guideline for the management of menorrhagia
      with clearly defined indications and contraindications&semi; 2) educating
      gynaecologists about UAE&semi; 3) composing a patient information leaflet and a
      website, and 4) arranging a protocol in a multidisciplinary team.

PMID- 21868812
TI  - Renal transplantation in patients with atypical haemolytic uraemic syndrome: a
      tailor made approach is necessary.
AB  - A 33-year-old woman with a history of chronic transplant dysfunction because of
      repeated bouts of haemolytic uraemic syndrome (HUS) was considered for a second
      transplant. Extensive genetic investigation of the complement system was executed
      to rule out known mutations prone to development of HUS. This case illustrates
      the importance of genetic screening in patients with recurrent HUS.

PMID- 21868813
TI  - A rare cause of congenital adrenal hyperplasia: Antley-Bixler syndrome due to POR
      deficiency.
AB  - Cytochrome P450 oxidoreductase (POR) deficiency is a recently discovered new
      variant of congenital adrenal hyperplasia. Distinctive features of POR deficiency
      are the presence of disorders of sexual development in both sexes, glucocorticoid
      deficiency and skeletal malformations similar to those observed in the Antley
      Bixler syndrome.

PMID- 21868814
TI  - A young woman with generalised lymphadenopathy. Systemic lupus erythematosus
      (SLE).

PMID- 21868815
TI  - An unusual cause of a usual presentation. Hantavirus infection.

PMID- 21868816
TI  - Multifocal adrenal nerve tissue? Adrenal ganglioneuroma.

PMID- 21868817
TI  - A bulky mass in an HIV-positive patient. Diffuse large B-cell lymphoma.

PMID- 21868818
TI  - The effects of implementation of the Surviving Sepsis Campaign in the
      Netherlands.
AB  - To reduce unintentional and avoidable adverse events in patients in hospitals in
      the Netherlands, a patient safety agency (VMS) programme was launched in 2008.
      Among the VMS topics, the programme 'optimal therapy in severe sepsis', according
      to the international Surviving Sepsis Campaign (SSC), aims to improve early
      diagnosis and treatment of sepsis to reduce sepsis mortality by 15% before the
      end of 2012. We analysed compliance data submitted to the international SSC
      database from the Netherlands and compared these data with published
      international SS C results. Data of 863 patients, representing 6% of the
      international data (n=14,209), were used for analysis. In the Netherlands, the
      resuscitation bundle compliance improved significantly from 7% at baseline to 27%
      after two years (p=0.002). Internationally, the resuscitation bundle compliance
      increased significantly from 11 to 31% (p.

PMID- 21868819
TI  - Factors influencing virus-host cell interplay.
AB  - The Conference on Retroviruses and Opportunistic Infections (CROI) provides an
      annual international forum for basic scientists and clinical and global health
      researchers to present and become current on the most recent advances in the
      field of HIV and AIDS research. The 18th conference contained a number of strong
      basic science sessions. HIV-1 infection of the cell is opposed by cellular
      factors that attack the viral replication cycle at various points. However, the
      virus has evolved defenses against these innate cellular antiviral proteins. CROI
      continues to be a strong forum for presentation of the most recent developments
      in this area of research. In addition, there were numerous presentations on
      cellular factors that regulate virus-host cell interplay as well as on research
      that is providing detailed insight into the mechanism of action of integrase
      inhibitors. Some presentations focused on approaches to studying and intervening
      with viral latency, particularly in primary cell models. Research on the use of
      zinc-finger nucleases to knock out CC chemokine receptor R5 expression in CD34+
      stem cells also received a lot of interest. The hope is that these strategies
      will provide new therapeutic approaches to generate resistance to HIV-1
      infection.

PMID- 21868820
TI  - HIV vaccine development.
AB  - Presentations at the 2011 Conference on Retroviruses and Opportunistic Infections
      reflected the resurging interest in antibody responses against HIV given the
      encouraging results of the Thai vaccine trial. A plenary talk and an entire
      symposium were devoted to HIV-specific antibody responses describing newly
      isolated, potent neutralizing monoclonal antibodies. These antibodies undergo
      extensive somatic mutation to achieve their remarkable neutralizing properties.
      Inducing these types of antibodies by vaccination, however, still represents a
      challenge. New data were presented suggesting that neutralizing antibodies, but
      not binding antibodies, can provide protection against infection in the nonhuman
      primate (NHP) model. Several interesting discoveries were also reported showing
      that cellular immune responses recognizing HLA-C and HLA class II molecules might
      also be important in control of viral replication. Finally, new vaccine studies
      in the NHP model showed that electroporated DNA, along with the adjuvant
      interleukin 12 may be an efficacious vaccine regimen.

PMID- 21868821
TI  - HIV epidemiology and breakthroughs in prevention 30 years into the AIDS epidemic.
AB  - Thirty years after the first AIDS cases were reported in the United States, the
      HIV epidemic continues to be heavily concentrated among men who have sex with men
      (MSM) in the United States. MSM are heavily impacted throughout most of the world
      and are the predominant risk group throughout the Americas and Western Europe;
      heterosexuals are the predominant risk group in sub-Saharan Africa; and injection
      drug users predominate throughout Eastern Europe and Southeast Asia. In the
      United States, blacks and Latinos continue to be disproportionately affected,
      despite overall advances in HIV testing and care. The 2011 Conference on
      Retroviruses and Opportunistic Infections focused on populations heavily impacted
      throughout the world: adolescents, women, MSM, and serodiscordant couples.
      Several presentations focused on the unique relationship between herpes simplex
      virus type 2 (HSV-2) and HIV-1; although many opportunistic infections increase
      HIV acquisition risk, HSV-2 is likely the only one whose effective prevention or
      treatment could substantially influence HIV infection rates, because of the high
      prevalence and persistence of HSV-2. The 2011 conference also celebrated the
      substantial advances made in the use of antiretroviral drugs for prevention of
      HIV acquisition (eg, oral preexposure prophylaxis, topical microbicides) and
      transmission (eg, antiretroviral therapy). Further progress is also being made in
      evaluating other prevention strategies and their rollout, including male condoms,
      male circumcision, and HIV testing and linkage to care.

PMID- 21868822
TI  - Central nervous system complications of HIV infection.
AB  - Issues relevant to the nervous system garnered substantial attention at the 18th
      Conference on Retroviruses and Opportunistic Infections. Several topics emerged
      as areas of importance both for informing current understanding of HIV-related
      neurologic disorders and their treatment, and for spurring future investigations.
      Measurable biomarkers of HIV-associated neurocognitive disorder (HAND) were a
      major theme, with studies ranging from new investigations of known laboratory and
      imaging markers to identification of novel molecules that might be investigated
      as potential means to follow disease activity as well as to better understand
      etiology of disease. Studies of pathogenesis of HAND and simian immunodeficiency
      virus-mediated neurologic injury added to prior understanding of lentivirus
      neuropathogenesis. Another broad area of investigation was the interplay between
      treatment with antiretroviral or adjunctive therapies and biomarkers of HAND. New
      data were presented on the potential importance of acute and early infection on
      the integrity of the central nervous system, complemented by studies of the
      effects of early treatment interventions.

PMID- 21868825
TI  - A hierarchical syntactic shape analyzer.
AB  - In many cases a picture is described in terms of various plane objects and their
      shape. This paper describes a parser whose input is a piecewise linear encoding
      of a contour and whose output is a string of high-level descriptions: arcs,
      corners, protrusions, intrusions, etc. Such a representation can be used not only
      for description but also for recognition. Previous syntactic techniques for
      contour description have often used high-level languages for the description of
      contours. This has been necessary in order to guarantee contour closure and
      eliminate the noise. In the present approach the numerical preprocessing of the
      contour removes most of the noise and also produces the answers to certain simple
      questions about its shape. Therefore, simpler grammars can be used for the
      contour description. Examples of descriptions of contours are given for
      handwritten numerals, white blood cells, and printed wiring circuit boards.

PMID- 21868823
TI  - Complications of HIV disease and antiretroviral therapy.
AB  - Studies on new direct-acting antivirals (DAAs) for hepatitis C virus infection
      were a focus of the 2011 Conference on Retroviruses and Opportunistic Infections.
      Although the majority of the data were from HIV-uninfected patients, much-needed
      work has begun to characterize DAA and antiretroviral drug interactions and to
      evaluate performance of DAAs for HIV/HCV-coinfected patients. There was continued
      emphasis on pathogenesis, management, and prevention of the long-term
      complications of HIV disease and its therapies, including cardiovascular disease,
      lipodystrophy, renal disease, and alterations in bone metabolism. Malignancies,
      particularly non-AIDS-defining cancers, have emerged as a leading complication
      and cause of death in HIV infection that may not be fully mitigated by immune
      reconstitution with antiretroviral therapy. This year's conference also
      highlighted important data on the optimal timing of antiretroviral therapy in
      tuberculosis coinfection, as well as the treatment and prevention of common
      coinfections including cryptococcal meningitis and influenza.

PMID- 21868824
TI  - Advances in antiretroviral therapy.
AB  - The 18th Conference on Retroviruses and Opportunistic Infections maintained its
      tradition of being the preeminent forum for detailing the state-of the-art in
      antiretroviral therapy. There were important presentations on investigational
      antiretroviral drugs, clinical trials in treatment-experienced patients, and new
      antiretroviral strategies. Relevant data on resistance to antiretroviral drugs
      and pharmacokinetic interactions were discussed. There were extensive
      presentations on antiretroviral therapy in resource-limited settings, including
      large-scale clinical trials, scale-up of antiretroviral therapy, adherence,
      retention in care, and treatment outcomes for children and adults. Prevention of
      mother-to-child transmission continued to be an important part of the conference.

PMID- 21868826
TI  - Decomposition of two-dimensional shapes by graph-theoretic clustering.
AB  - This paper describes a technique for transforming a twodimensional shape into a
      binary relation whose clusters represent the intuitively pleasing simple parts of
      the shape. The binary relation can be defined on the set of boundary points of
      the shape or on the set of line segments of a piecewise linear approximation to
      the boundary. The relation includes all pairs of vertices (or segments) such that
      the line segment joining the pair lies entirely interior to the boundary of the
      shape. The graph-theoretic clustering method first determines dense regions,
      which are local regions of high compactness, and then forms clusters by merging
      together those dense regions having high enough overlap. Using this procedure on
      handdrawn colon shapes copied from an X-ray and on handprinted characters, the
      parts determined by the clustering often correspond well to decompositions that a
      human might make.

PMID- 21868827
TI  - A description method of handprinted chinese characters.
AB  - A description method of handprinted Chinese characters is presented. In the
      method, a Chinese character is composed of some partial patterns which are
      constructed using the concatenate relation, cross relation, and near relation.
      The relations of relative location among partial patterns are used for
      categorization of the partial pattems. A Chinese character is expressed from the
      results of categorization.

PMID- 21868828
TI  - An intrinsic dimensionality estimator from near-neighbor information.
AB  - The intrinsic dimensionality of a set of patterns is important in determining an
      appropriate number of features for representing the data and whether a reasonable
      two- or three-dimensional representation of the data exists. We propose an
      intuitively appealing, noniterative estimator for intrinsic dimensionality which
      is based on nearneighbor information. We give plausible arguments supporting the
      consistency of this estimator. The method works well in identifying the true
      dimensionality for a variety of artificial data sets and is fairly insensitive to
      the number of samples and to the algorithmic parameters. Comparisons between this
      new method and the global eigenvalue approach demonstrate the utility of our
      estimator.

PMID- 21868829
TI  - An optimal frequency domain filter for edge detection in digital pictures.
AB  - Edge detection and enhancement are widely used in image processing applications.
      In this paper we consider the problem of optimizing spatial frequency domain
      filters for detecting edges in digital pictures. The filter is optimum in that it
      produces maximum energy within a resolution interval of specified width in the
      vicinity of the edge. We show that, in the continuous case, the filter transfer
      function is specified in terms of the prolate spheroidal wave function. In the
      discrete case, the filter transfer function is specified in terms of the sampled
      values of the first-order prolate spheroidal wave function or in terms of the
      sampled values of an asymptotic approximation of the wave function. Both versions
      can be implemented via the fast Fourier transform (FFT). We show that the optimum
      filter is very effective for detecting blufred and noisy edges. Finally, we
      compare the performance of the optimum edge detection filter with other edge
      detection filters using a variety of input images.

PMID- 21868830
TI  - Organization and access of image data by areas.
AB  - This paper concerns methods for indexing areas in twodimensional array data. A
      method for naming subpictures from rasterscan image data is presented with
      notation that eases their subsequent storage access. Equations are given for
      converting each subpicture name into a storage-location pointer. A function
      ''NUMERIC'' is described that aids this task. Algorithms enabling efficient
      retrieval of subpicture areas from sequential and direct access files are
      presented. Examples are given that show that improved retrieval response is
      possible from using NUMERIC to sort lists of areas to be recalled. The paper
      includes an overview of tree data structures, the subject implemented by these
      techniques. An overlapping picture subareas storage scheme is discussed.

PMID- 21868831
TI  - Shape matching using relaxation techniques.
AB  - The problem of finding approximate matches of pieces of shapes to parts of larger
      shapes is investigated. The shapes are represented by polygonal approximations.
      Initially, figures of merit are assigned to the matches between pairs of angles
      on the two shapes. Relaxation methods are then used to find acceptable
      combinations of these matches. This approach was tested on a data base consisting
      of digitized coastlines in various map projections. In nearly all cases, all
      matches except the correct one were eliminated by the relaxation processes.

PMID- 21868832
TI  - Hierarchical representation of waveforms.
AB  - Ehrich and Foith have proposed an approach to the hierarchical representation of
      waveforms based on peak dominance relations. This correspondence proposes an
      alternative approach, derived from concepts of fuzzy connectedness. It also
      discusses the possibility of extending this approach to the description of curves
      and of images.

PMID- 21868833
TI  - Multivariate autoregressive feature extraction and the recognition of
      multichannel waveforms.
AB  - It is proposed that the autoregressive coefficient matrices appearing in a
      multivariate autoregressive model fitting may be used for feature extraction
      purposes in problems concerning recognition of multichannel waveforms. It is
      demonstrated how the information contained in the autoregressive parameters may
      be further compressed by applying the ordinary or a modified Karhunen-Loeve
      expansion. The feature extraction procedures are illustrated on a large data base
      of seismic wave traces originating from shallow earthquakes and underground
      nuclear explosions. The results obtained (using a multivariate Gaussian
      classification algorithm) suggest that the combined autore-gressive/Karhunen
      Loeve method has a considerably larger discrimination potential than the more
      conventional seismic discriminants.

PMID- 21868834
TI  - A dynamic programming algorithm for the distance between two finite areas.
AB  - The problems of speech recognition and orthographic word correction have been
      greatly mitigated by the use of dynamic programming techniques for finding the
      distance between two finite sequences. This paper extends the technique into two
      dimensions, and presents an algorithm for finding the distance between two finite
      areas. Applications of the algorithm are suggested.

PMID- 21868835
TI  - Thinning algorithms for gray-scale pictures.
AB  - Elongated black objects in black-and-white pictures can be ''thinned'' to arcs
      and curves, without changing their connectedness, by (repeatedly) deleting black
      border points whose deletion does not locally disconnect the black points in
      their neighborhoods. This technique generalizes to gray-scale pictures if we use
      a weighted definition of connectedness: two points are ''connected'' if there is
      a path joining them on which no point is lighter than either of them. We can then
      ''thin'' dark objects by changing each point's gray level to the minimum of its
      neighbors' gray levels, provided this does not disconnect any pair of points in
      its neighborhood. Examples illustrating the performance of this technique are
      given.

PMID- 21868836
TI  - Recursive implementation of a two-step nonparametric decision rule.
AB  - The two-step approach to nonparametric discrimination is that of estimating class
      conditional densities and deriving the Bayes decision rule as if the estimates
      were true. Direct implementation of such a decision rule ecounters two
      computational problems. Complexity increases with sample size, and finite
      precision limits the decision rule domain. Here a recursive algorithm to reduce
      the expected number of operations and word-length limitations below that of the
      direct approach is developed. A special case of the formulation reduces to the
      weighted k-nearest-neighbor rule.

PMID- 21868837
TI  - Construction of natural language sentence acceptors by a supervised-learning
      technique.
AB  - The problem discussed here is to build automatically an acceptor for natural
      language sentences, a sample of sentences being given. We solve it in the context
      of computer-assisted instruction and database interrogation. This paper is
      focused toward the definition of a learning criterion, i.e., a quality measure on
      the set of the acceptors which are compatible with the sample.

PMID- 21868838
TI  - A Generalization of DPCM for Digital Image Compression.
AB  - A natural generalization of two-dimensional digital pulsecode modulations (DPCM)
      has been used to handle the compression of images for human eyes only. It shows
      that by ignoring the mean-square error (MSE) and wisely arranging the errors in
      the right place, a simple method can achieve very good results.

PMID- 21868839
TI  - Matching segments of images.
AB  - This correspondence describes research in the development of symbolic
      registration techniques directed toward the comparison of pairs of images of the
      same scene to ultimately generate descriptions of the changes in the scene.
      Unlike most earlier work in image registration, all the matching and analysis
      will be performed at a symbolic level rather than a signal level. We have applied
      this registration procedure on several different types of scenes and the system
      appears to work well both on pairs of images which may be analyzed in part by
      signal based systems and those which cannot be so analyzed.

PMID- 21868840
TI  - A family of similarity measures between two strings.
AB  - We present a class of similarity measures for quantitatively comparing two
      strings, that is, two linearly ordered sets of elements. The strings can be of
      different lengths, the elements come from a single alphabet, and an element may
      appear any number of times. The limiting values of each measure are 0, when two
      completely different strings are compared, and 1, when the two strings are
      identical. Applications of similarity measures are numerous in nonnumerical
      computations, such as in heuristic search processes in associative networks, in
      pattern recognition and classification, in game playing programs, and in music
      and text analysis. We offer a number of feasible measures from among which some
      are discarded on plausibility grounds. One can select the measure most adequate
      for one's needs on the basis of a few characteristic examples of strings compared
      and by considering the specific requirements of the application at hand.

PMID- 21868841
TI  - Computer tracking of objects moving in space.
AB  - A method is developed to represent movement of convex blocks in three-dimensional
      space from a sequence of two-dimensional camera images. The goals are to
      determine the objects' movement toward or away from the camera as well as
      left/right and up/down movement in the image plane and to build models of the
      blocks. The movement information is used as part of a hierarchical matching
      process that determines the correspondence of blocks between scenes.

PMID- 21868842
TI  - A syntactic-semantic approach to image understanding and creation.
AB  - A syntactic-semantic approach to information extraction from images is described.
      The methodology involves the injection of semantic considerations into context
      free grammars. The semantic considerations include feature vectors, selection
      restrictions, feature transfer functions, semantic well-formedness, etc. With
      such injection, we can make a description scheme which carries the numerical, the
      structural, and the a prior real world knowledge about the pattern we want to
      extract. From the description we can construct an analytical mechanism, the
      creation machine, which wil find the desired pattern amid a chaos of noisy
      primitives.

PMID- 21868843
TI  - Operations on images using quad trees.
AB  - A quad tree for representing a picture is a tree in which successively deeper
      levels represent successively finer subdivisions of picture area. An algorithm is
      given for superposing N quad trees in time proportional to the total number of
      nodes in the trees. Warnock-type algorithms are then presented for building the
      quad tree for the picture of the boundary of a polygon, and for coloring the
      interior of such a polygon. These algorithms take O(v + p + q) time, where v is
      the number of polygon vertices, p is the polygon perimeter, and q is a resolution
      parameter. When the resolution q is fixed, these algorithms are asymptotically
      optimal.

PMID- 21868844
TI  - Syntactic decision rules for recognition of spoken words and phrases using a
      stochastic automaton.
AB  - This study deals with the design of a syntactic decision rule for recognizing an
      unknown utterance from a set X. The decision rule is expressed as a function of
      the character string (CS) derived from the test utterance. To obtain the CS, the
      waveform of the utterance is divided into a large number of frames of roughly
      equal duration numbered 1, 2,...,n. The ith symbol in the CS is the phonemic
      symbol obtained by subjecting the ith frame of the waveform to a relatively
      simple phoneme decision rule, the number of symbols in the CS being n. All the
      available nonacoustic information such as the lexicon of words in the set X, the
      possibility of confusion between different phonemes as seen by the phoneme
      decision rule, etc. is used in the design of the decision rule. The syntactic
      decision rule can be implemented by a stochastic finite state automaton involving
      limited memory and computation. The decision rule can also be interpreted as
      yielding the phrase x which minimizes a distance measure D(x, z) between the
      phrase x X and the observed CS z. We wili compare this approach with the other
      approaches such as the Viterbi methods, the distance approaches involving various
      types of distances, etc.

PMID- 21868845
TI  - n-Gram Statistics for Natural Language Understanding and Text Processing.
AB  - n-gram (n = 1 to 5) statistics and other properties of the English language were
      derived for applications in natural language understanding and text processing.
      They were computed from a well-known corpus composed of 1 million word samples.
      Similar properties were also derived from the most frequent 1000 words of three
      other corpuses. The positional distributions of n-grams obtained in the present
      study are discussed. Statistical studies on word length and trends of n-gram
      frequencies versus vocabulary are presented. In addition to a survey of n-gram
      statistics found in the literature, a collection of n-gram statistics obtained by
      other researchers is reviewed and compared.

PMID- 21868846
TI  - The consistent labeling problem: part I.
AB  - In this first part of a two-part paper we introduce a general consistent labeling
      problem based on a unit constraint relation T containing N-tuples of units which
      constrain one another, and a compatibility relation R containing N-tuples of unit
      label pairs specifying which N-tuples of units are compatible with which N-tuples
      of labels. We show that Latin square puzzles, finding N-ary relations, graph or
      auto-mata homomorphisms, graph colorings, as well as determining satisfiability
      of propositional logic statements and solving scene and edge labeling problems,
      are all special cases of the general consistent labeling problem. We then discuss
      the various approaches that researchers have used to speed up the tree search
      required to find consistent labelings. Each of these approaches uses a particular
      look-ahead operator to help eliminate backtracking in the tree search. Finally,
      we define the ?KP two-parameter class of look-ahead operators which includes, as
      special cases, the operators other researchers have used.

PMID- 21868847
TI  - Experiments in text recognition with the modified viterbi algorithm.
AB  - In this paper a modification of the Viterbi algorithm is formally described, and
      a measure of its complexity is derived. The modified algorithm uses aheuristic to
      limit the search through a directed graph or trellis. The effectiveness of the
      algorithm is investigated via exhaustive experimentation on an input of machine
      printed text. The algorithm assumes language to be a Markov chain and uses
      transition probabilities between characters. The results empirically answer the
      long-standing question of what is the benefit, if any, of using transition
      probabilities that depend on the length of a word and their position in it.

PMID- 21868848
TI  - Problem-solving models and search strategies for pattern recognition.
AB  - Noting the major limitations of multivariate statistical classification and
      syntactic pattern recognition models, this paper presents an overview of some
      recent work using alternate representations for multistage and nearest neighbor
      multiclass classification, and for structural analysis and feature extraction.
      These alternate representations are based on generalizations of state-space and
      AND/OR graph models and search strategies developed in artificial intelligence
      (AI). The paper also briefly touches on other current interactions and
      differences between artificial intelligence and pattern recognition.

PMID- 21868849
TI  - A Generalized Line and Junction Labeling Scheme with Application to scene
      Analysis.
AB  - A line and junction labeling scheme is introduced that is valid for both planar
      and curved-surface bodies. Seven generalized junction types are defined and shown
      to cover all valid projections for a wide class of planar and curved-surface
      bodies. It is further shown that there are limitations on the permissible
      junction types as one moves from one end of a line segment to the other. The
      valid junction transitions provide 1) a new set of edge semantics for line
      labeling and 2) an ability to verify whether a given sequence of junctions forms
      a realizable configuration.

PMID- 21868850
TI  - On the analysis of accumulative difference pictures from image sequences of real
      world scenes.
AB  - The count of events where sample areas from the second and subsequent frames of a
      TV-image sequence are incompatible with the corresponding sample area of the
      first frame are accumulated in a first-order difference picture (FODP). Analysis
      of this FODP provides a separate estimate for images of moving objects and of
      stationary scene components. We start from the hypothesis that the first frame
      represents the stationary scene component. Once it has been recognized that a
      subarea of this initial estimate corresponds to the image of a moving object, the
      grey values in this subarea are replaced by later estimates of the stationary
      background at this position. No knowledge specific to a particular scene is
      utilized in the algorithm. The results for two scene sequences are presented.

PMID- 21868851
TI  - Design of a special interpreter for the classification of human chromosomes.
AB  - The use of new staining methods and the large amount of investigations for human
      chromosomes has created a need for a useful automated chromosome analysis.
      Because of the lack of accuracy of the existing systems, a new approach is given.
      The problems in the different stages of the classification process are described.
      A comparison of the decision-statistical, syntactical, and interpretative
      approach is discussed. A system realization for the total karyotyping of
      chromosomes, based on the interpretative approach, is described in more detail.
      Guided by one of the models in the world model structure, a current description
      is recognized in a three-phase interpreter.

PMID- 21868852
TI  - A cluster separation measure.
AB  - A measure is presented which indicates the similarity of clusters which are
      assumed to have a data density which is a decreasing function of distance from a
      vector characteristic of the cluster. The measure can be used to infer the
      appropriateness of data partitions and can therefore be used to compare relative
      appropriateness of various divisions of the data. The measure does not depend on
      either the number of clusters analyzed nor the method of partitioning of the data
      and can be used to guide a cluster seeking algorithm.

PMID- 21868853
TI  - Image feature extraction using diameter-limited gradient direction histograms.
AB  - Features extracted by operators which examine diameter-limited gradient direction
      histograms are important because they describe images of industrial workpieces
      efficiently and have the potential for rapid computation via special purpose
      hardware. When such operators are passed over an image in raster fashion,
      features such as the following are detected: a strong peak in the direction
      histogram indicating the presence of a relatively straight edge, a second strong
      direction indicating a corner, a wide direction group indicating a curved edge,
      and a uniform distribution of directions over the histogram indicating small
      holes. Diameter-limited optimization can be used to substantially reduce the
      number of pixels which have been given feature labels by such operators without
      losing descriptive power. Feature labels for direction histograms having a second
      strong direction, a wide direction group, or a uniform distribution might be
      retained only if all other pixels within a circular aperture have a lower bin
      value. Pixels with a strong direction label might be retained only if all other
      pixels within a circular aperture and along the gradient direction have a smaller
      bin value. Tracking can then be applied to the remaining strong direction pixels
      in the direction perpendicular to the gradient to achieve representation of edges
      by endpoints. Experimental results indicate that descriptions which are
      compatible with human interpretation can be achieved.

PMID- 21868854
TI  - PFS Clustering Method.
AB  - This paper presents a method of cluster analysis based on a pseudo F-statistic
      (PFS) criterion function. It is designed to subdivide an ensemble into an optimal
      set of groups, where the number of groups is not specified and no ad hoc
      parameters are employed. Univariate and multivariate F-statistic and pseudo F
      statistic consistency is displayed. Algorithms for feasible application of PFS
      are given. Results from simulations are utilized to demonstrate the capabilities
      of the PFS clustering method and to provide a comparative guide for other users.

PMID- 21868855
TI  - A method of recognition and representation of korean characters by tree grammars.
AB  - A syntactic method is applied to the recognition of Korean characters (Hangul).
      Since they develop into complex characters by the sequential addition of
      fundamental characters under positioning rules, there are a large amount of
      characters and consequently there exist many similar characters. Therefore, the
      sequential extraction, according to the positioning rules, of fundamental
      characters composing Korean characters is effective for automatic recognition. As
      a structural analysis, a production process of fundamental characters is
      represented by tree grammars, and the extraction algorithm of fundamental
      characters and the results of computer simulation are described.

PMID- 21868856
TI  - Texture analysis using generalized co-occurrence matrices.
AB  - We present a new approach to texture analysis based on the spatial distribution
      of local features in unsegmented textures. The textures are described using
      features derived from generalized co-occurrence matrices (GCM). A GCM is
      determined by a spatial constraint predicate F and a set of local features P =
      {(Xi, Yi, di), i = 1,..., m} where (Xi, Yi) is the location of the ith feature,
      and di is a description of the ith feature. The GCM of P under F, GF, is defined
      by GF(i, j) = number of pairs, pk, pl such that F(pk, pl) is true and di and dj
      are the descriptions of pk and pl, respectively. We discuss features derived from
      GCM's and present an experimental study using natural textures.

PMID- 21868857
TI  - Use of range and reflectance data to find planar surface regions.
AB  - This paper describes a sequential procedure for processing registered range and
      intensity data to detect and extract regions that correspond to planar surfaces
      in a scene.

PMID- 21868858
TI  - A random walk procedure for texture discrimination.
AB  - We consider the problem of texture discrimination. Random walks are performed in
      a plain domain D bounded by an absorbing boundary ? and the absorption
      distribution is calculated. Measurements derived from such distributions are the
      features used for discrimination. Both problems of texture discrimination and
      edge segment detection can be solved using the same random walk approach. The
      border distributions and their differences with respect to a homogeneous image
      can classify two different images as having similar or dissimilar textures. The
      existence of an edge segment is concluded if the boundary distribution for a
      given window (subimage) differs significantly from the boundary distribution for
      a homogeneous (uniform grey level) window. The random walk procedure has been
      implemented and results of texture discrimination are shown. A comparison is made
      between results obtained using the random walk approach and the first-or second
      order statistics, respectively. The random walk procedure is intended mainly for
      the texture discrimination problem, and its possible application to the edge
      detection problem (as shown in this paper) is just a by-product.

PMID- 21868859
TI  - Translation of fuzzy queries for relational database system.
AB  - The concept of a database skeleton which reflects both the user's conception of
      the real world and the system's understanding of the interrelationships among
      database entities is described. It consists of a conceptual schema (conceptual
      graphs) and a relational schema (information graph). With the aid of the database
      skeleton, fuzzy queries can be translated and disambiguated by analyzing the
      queries using the conceptual graphs of a database skeleton. The query language
      XQL is introduced, and the XQL translator is described in some detail.

PMID- 21868860
TI  - Decomposition of three-dimensional objects into spheres.
AB  - Algorithms are presented for converting between different three-dimensional
      object representations: from a collection of cross section outlines to surface
      points, and from surface points to a collection of overlapping spheres. The
      algorithms effect a conversion from surface representations (outlines or surface
      points) to a volume representation (spheres). The spherical representation can be
      useful for graphical display, and perhaps as an intermediate representation for
      conversions to representations with other primitives. The spherical decomposition
      also permits the computation of points on the symmetric surface of an object, the
      three-dimensional analog of Blum's symmetric axis. The algorithms work in real
      coordinates rather than in a discrete space, and so avoid error introduced by the
      quantization of the space.

PMID- 21868861
TI  - A problem of dimensionality: a simple example.
AB  - In pattern recognition problems it has been noted that beyond a certain point the
      inclusion of additional parameters (that have been estimated) leads to higher
      probabilities of error. A simple problem has been formulated where the
      probability of error approaches zero as the dimensionality increases and all the
      parameters are known; on the other hand, the probability of error approaches one
      half as the dimensionality increases and parameters are estimated.

PMID- 21868862
TI  - The use of a syntactic shape analyzer for contour matching.
AB  - Description of contours in terms of complex arcs allows the use of simple
      algorithms for matching. An example of such matchings for island contours is
      included.

PMID- 21868863
TI  - Comment on ''a declustering criterion for feature extraction in pattern
      recognition''.
AB  - The purpose of this correspondence is to point out that the scaling procedure (as
      well as any nonsingular transformation) described in Section VI of the above
      paper1 is unnecessary.

PMID- 21868864
TI  - Geometric constructions for predicting hough transform performance.
AB  - Graphical techniques are presented for estimating Hough transform performance for
      detecting straight lines in noisy digital pictures. The methods show explicitly
      the influence of noise due, for example, to quantizing errors on the accuracy of
      estimating the underlying sets of collinear points. Exact bounds are obtained for
      sets of collinear points showing that under quite general conditions only the
      endpoints are of significance. Theorems governing grid size for the accumulator
      method are given.

PMID- 21868865
TI  - Peak detection using difference operators.
AB  - Complex waveforms may contain peaks and valleys at many different scales, ranging
      from very local to very global. This correspondence describes an approach to
      detecting these peaks and valleys by applying simple difference operators at each
      point to neighborhoods having a wide range of sizes, and making simple
      comparisons of the outputs of these operators for various sizes and positions.

PMID- 21868866
TI  - Performance comparison of scene matching techniques.
AB  - The problem of matching two images of the same scene, taken by different sensors
      under different viewing geometries, is a challenging problem in the field of
      image processing and pattern recognition. The scenes are usually transformed so
      drastically by the different viewing geometries and sensor characteristics that
      it is extremely difficult, if not impossible, to match the original images
      without the proper data processing. Geometric and intensity transformations must
      be performed to bring the matching elements and their intensity into a one-to-one
      correspondence. Objects of interest represented by subimages of one scene were
      located in the other using scene matching techniques with intensity difference
      and edge features as measurement features. Performance characteristics of the
      matches by these techniques are presented in terms of the probability of a match
      as a function of the probability of false fix.

PMID- 21868867
TI  - A coding method of chinese characters.
AB  - In this paper we propose a coding method of handprinted Chinese characters in
      which, defining a grammar, the process of block categorization is made to
      correspond to a process of sentential generation. We obtain two strings of
      production rules and block codes being equivalent to the descriptions of the
      structure and internal components of a character pattern, and a Chinese character
      is encoded effectively by the use of these two strings. It is shown that this
      coding method is available for the classification and discrimination of
      handprinted Chinese characters.

PMID- 21868868
TI  - DECA: A Discrete-Valued Data Clustering Algorithm.
AB  - This paper presents a new clustering algorithm for analyzing unordered discrete
      valued data. This algorithm consists of a cluster initiation phase and a sample
      regrouping phase. The first phase is based on a data-directed valley detection
      process utilizing the optimal second-order product approximation of high-order
      discrete probability distribution, together with a distance measure for discrete
      valued data. As for the second phase, it involves the iterative application of
      the Bayes' decision rule based on subgroup discrete distributions. Since
      probability is used as its major decision criterion, the proposed method
      minimizes the disadvantages of yielding solutions sensitive to the arbitrary
      distance measure adopted. The performance of the proposed algorithm is evaluated
      by applying it to four different sets of simulated data and a set of clinical
      data. For performance comparison, the decision-directed algorithm [11] is also
      applied to the same set of data. These evaluation experiments fully demonstrate
      the validity and the operational feasibility of the proposed algorithm and its
      superiority as compared to the decision-directed algorithm.

PMID- 21868869
TI  - Capacity and error estimates for boolean classifiers with limited complexity.
AB  - This paper extends the notions of capacity and distribution-free error estimation
      to nonlinear Boolean classifiers on patterns with binary-valued features. We
      establish quantitative relationships between the dimensionality of the feature
      vectors (d), the combinational complexity of the decision rule (c), the number of
      samples in the training set (n), and the classification performance of the
      resulting classifier. Our results state that the discriminating capacity of
      Boolean classifiers is given by the product dc, and the probability of ambiguous
      generalization is asymptotically given by (n/dc 1)-i 0(1Og d)/d) for large d, and
      n = O(dc). In addition we show that if a fraction v of the training samples is
      misclassified then the probability of error (r) in subsequent samples satisfies
      P(17r - vl > e) : 2.773 exp (dc - e2n/8) for all distributions, regardless of how
      the classifier was discovered.

PMID- 21868870
TI  - A sinusoidal family of unitary transforms.
AB  - A new family of unitary transforms is introduced. It is shown that the well-known
      discrete Fourier, cosine, sine, and the Karhunen-Loeve (KL) (for first-order
      stationary Markov processes) transforms are members of this family. All the
      member transforms of this family are sinusoidal sequences that are asymptotically
      equivalent. For finite-length data, these transforms provide different
      approximations to the KL transform of the said data. From the theory of these
      transforms some well-known facts about orthogonal transforms are easily explained
      and some widely misunderstood concepts are brought to light. For example, the
      near-optimal behavior of the even discrete cosine transform to the KL transform
      of first-order Markov processes is explained and, at the same time, it is shown
      that this transform is not always such a good (or near-optimal) approximation to
      the above-mentioned KL transform. It is also shown that each member of the
      sinusoidal family is the KL transform of a unique, first-order, non-stationary
      (in general), Markov process. Asymptotic equivalence and other interesting
      properties of these transforms can be studied by analyzing the underlying Markov
      processes.

PMID- 21868871
TI  - Asymptotic properties of discrete unitary transforms.
AB  - A method for studying the asymptotic behavior of discrete transformations is
      developed using numerical quadrature theory. This method allows a more convenient
      examination of the correlation properties of common unitary transforms for large
      block sizes. As a practical result of this method it is shown that the discrete
      cosine transform is asymptotically optimal for all finite-order Markov signals.

PMID- 21868872
TI  - Maximum likelihood estimation of markov-process blob boundaries in noisy images.
AB  - Effective and elegant procedures have recently appeared in the published
      literature for determining by computer a highly variable blob boundary in a noisy
      image [1]-[3]. In this paper we point out that if the blob boundary is modeled as
      a Markov process and the additive noise is modeled as a white Gaussian noise
      field, then maximization of the joint likelihood of the hypothesized blob
      boundary and all of the image data results in roughly the same blob boundary
      determination as does one of the aforementioned deterministic formulations [2].
      However, the formulation in this paper provides insights into and optimal
      parameter values for the functions involved and reveals suboptimalities in some
      of the formulations appearing in the literature. More generally, we agree that
      maximization of the joint likelihood of the hypothesized blob boundary and of the
      entire picture function is a fundamental approach to boundary estimation or the
      estimation of linear features (roads, rivers, etc.) in images, and provides a
      powerful mechanism for designing sequential, parallel, or other boundary
      estimation algorithms. The ripple filter, an advanced form of region growing, is
      briefly introduced and illustrates one of a number of alternative algorithms for
      maximizing the likelihood function. Hence, this likelihood maximization approach
      provides a unified view for seemingly different approaches, such as sequential
      boundary finding and region growing. Bounds on the accuracy of boundary
      estimation are readily derived with this formulation and are presented.

PMID- 21868873
TI  - Digital image and spectrum restoration by quadratic programming and by modified
      fourier transformation.
AB  - We consider the convolution equation f * h + e = d, where f is sought, h is a
      known ''point spread function,'' e represents random errors, and d is the
      measured data. All these functions are defined on the integers mod(N). A
      mathematical-statistical fonnulation of the problem leads to minff * hdA, where
      the A-norm is derived from the statistical distribution of e. If f is known to be
      nonnegative, this is a quadratic progamming problem. Using the discrete Fourier
      transforms (DFT's) F, H, and D of f, h, and d, we arrive at a minimization in
      another norm: minF F . H-D ?. A solution would be F = D/H, but H has zeros. We
      consider the theoretical and practical difficulties that arise from these zeros
      and describe two methods for calculating F numerically also when H has zeros.
      Numerical tests of the methods are presented, in particular tests with one of the
      methods, called ''the derivative method,'' where d is a blurred image.

PMID- 21868874
TI  - A variation on a nonparametric clustering method.
AB  - A single modification to a mode-seeking clustering algorithm proposed by Koontz,
      Narendra, and Fukunaga is shown to generate a novel clustering and to provide an
      indication of cluster stability. The modified method should provide better
      clusterings for ''uniform, touching'' clusters than the original, although the
      original should work better than the modified method for ''touching Gaussian''
      clusters. Suitable ranges for the clustering parameters of both methods are
      investigated. Since the modification requires changing only one line of the
      original algorithm, two clusterings can be obtained for the price of one coding.

PMID- 21868875
TI  - Comments on ''a quantitative study of the orientation bias of some edge detector
      schemes''.

PMID- 21868876
TI  - On the nonseparability of image models.
AB  - Jain and Angel's proof of nonseparability of the nearest neighbor model is
      discussed. A simple and helpful method is given to investigate the
      (non)separability of the autocorrelation of arbitrary two-dimensional image
      models.

PMID- 21868877
TI  - A dual method for maximum entropy restoration.
AB  - A simple iterative dual algorithm for maximum entropy image restoration is
      presented. The dual algorithm involves fewer parameters than conventional
      minimization in the image space. Mini-computer test results for Fourier synthesis
      with inadequate phantom data are given.

PMID- 21868878
TI  - A Simplified Derivation of Frei's Histogram Hyperbolization for Image
      Enhancement.
AB  - Frei has recently introduced a new technique (histogram hyperbolization) for
      image enhancement by the manipulation of the picture brightness levels. An
      alternative derivation of Frei's result, both simpler and more general, is
      presented.

PMID- 21868879
TI  - Some decision problems for bottom-up triangle acceptors.
AB  - It is proved that the emptiness problem for deterministic bottom-up triangle
      acceptors (BTA's) over a single input symbol is recursively unsolvable. From this
      result, it is also shown that certain decision problems involving BTA's and BPA's
      (deterministic bottom-up pyramid acceptors) are unsolvable.

PMID- 21868880
TI  - The relationship of the bayes risk to certain separability measures in normal
      classification.
AB  - For the problem of classifying an element (e.g., an unknown pattern) into one of
      two given categories where the associated observables are distributed according
      to one of two known multivariate normal populations having a common covariance
      matrix, it is shown that the minimum Bayes risk is a strict monotonic function of
      certain separability or statistical distance measures regardless of the a priori
      probabilities and the assigned loss function. However, for the associated
      conditional expected losses, strict monotonicity holds, if and only if a certain
      condition dependent on these probabilities and the given loss function is
      satisfied. These results remain valid for classification problems in which the
      observable can be transformed by a one-to-one differentiable mapping to
      normality.

PMID- 21868881
TI  - Locally trained piecewise linear classifiers.
AB  - We describe a versatile technique for designing computer algorithms for
      separating multiple-dimensional data (feature vectors) into two classes. We refer
      to these algorithms as classifiers. Our classifiers achieve nearly Bayes-minimum
      error rates while requiring relatively small amounts of memory. Our design
      procedure finds a set of close-opposed pairs of clusters of data. From these
      pairs the procedure generates a piecewise-linear approximation of the Bayes
      optimum decision surface. A window training procedure on each linear segment of
      the approximation provides great flexibility of design over a wide range of class
      densities. The data consumed in the training of each segment are restricted to
      just those data lying near that segment, which makes possible the construction of
      efficient data bases for the training process. Interactive simplification of the
      classifier is facilitated by an adjacency matrix and an incidence matrix. The
      adjacency matrix describes the interrelationships of the linear segments {Li}.
      The incidence matrix describes the interrelationships among the polyhedrons
      formed by the hyperplanes containing {Li}. We exploit switching theory to
      minimize the decision logic.

PMID- 21868882
TI  - A structural model of shape.
AB  - Shape description and recognition is an important and interesting problem in
      scene analysis. Our approach to shape description is a formal model of a shape
      consisting of a set of primitives, their properties, and their
      interrelationships. The primitives are the simple parts and intrusions of the
      shape which can be derived through the graph-theoretic clustering procedure
      described in [31]. The interrelationships are two ternary relations on the
      primitives: the intrusion relation which relates two simple parts that join to
      the intrusion they surround and the protrusion relation which relates two
      intrusions to the protrusion between them. Using this model, a shape matching
      procedure that uses a tree search with look-ahead to find mappings from a
      prototype shape to a candidate shape has been developed. An experimental Snobol4
      implementation has been used to test the program on hand-printed character data
      with favorable results.

PMID- 21868883
TI  - Three-dimensional moment invariants.
AB  - Recognition of three-dimensional objects independent of size, position, and
      orientation is an important and difficult problem of scene analysis. The use of
      three-dimensional moment invariants is proposed as a solution. The generalization
      of the results of two-dimensional moment invariants which had linked two
      dimensional moments to binary quantics is done by linking three-dimensional
      moments to ternary quantics. The existence and number of nth order moments in two
      and three dimensions is explored. Algebraic invariants of several ternary forms
      under different orthogonal transformations are derived by using the invariant
      property of coefficients of ternary forms. The result is a set of three
      dimensional moment invariants which are invariant under size, orientation, and
      position change. This property is highly significant in compressing the data
      which are needed in three-dimensional object recognition. Empirical examples are
      also given.

PMID- 21868884
TI  - Use of fuzzy algorithms for phonetic and phonemic labeling of continuous speech.
AB  - A model for assigning phonetic and phonemic labels to speech segments is
      presented. The system executes fuzzy algorithms that assign degrees of worthiness
      to structured interpretations of syllabic segments extracted from the signal of a
      spoken sentence. The knowledge source is a series of syntactic rules whose
      syntactic categories are phonetic and phonemic features detected by a
      precategorical and a categorical classification of speech sounds. Rules inferred
      from experiments and results for male and female voices are presented.

PMID- 21868886
TI  - Pattern recognition as conceptual morphogenesis.
AB  - Pattern recognition is our mental activity in which we formulate, select, modify,
      and adjust our concepts or our frames of reference so that we can see a ''form''
      in objects. We can tentatively formulate this viewpoint as the principle of
      minimum entropy (or entropy-like function). Different algorithms in clustering
      and pattern recognition are given new interpretations in the light of this
      unifying principle.

PMID- 21868885
TI  - Pattern-Based Interactive Diagnosis of Multiple Disorders: The MEDAS System.
AB  - A knowledge-based interactive sequential diagnostic system is introduced which
      provides for diagnosis of multiple disorders in several body systems. The
      knowledge base consists of disorder patterns in a hierarchical structure that
      constitute the background medical information required for diagnosis in the
      domain under consideration (emergency and critical care medicine, in our case).
      Utilizing this knowledge base, the diagnostic process is driven by a
      multimembership classification algorithm for diagnostic assessment as well as for
      information acquisition [1]. A key characteristic of the system is congenial man
      machine interface which comes to expression in, for instance, the flexibility it
      offers to the user in controlling its operation. At any stage of the diagnostic
      process the user may decide on an operation strategy that varies from full user
      control, through mixed initiative to full system control. Likewise, the system is
      capable of explaining to the user the reasoning process for its decisions. The
      model is independent of the knowledge base, thereby permitting continuous update
      of the knowledge base, as well as expansions to include disorders from other
      disciplines. The information structure lends itself to compact storage and
      provides for efflcient computation. Presently, the system contains 53 high-level
      disorders which are diagnosed by means of 587 medical findings.

PMID- 21868887
TI  - Digital image enhancement and noise filtering by use of local statistics.
AB  - Computational techniques involving contrast enhancement and noise filtering on
      two-dimensional image arrays are developed based on their local mean and
      variance. These algorithms are nonrecursive and do not require the use of any
      kind of transform. They share the same characteristics in that each pixel is
      processed independently. Consequently, this approach has an obvious advantage
      when used in real-time digital image processing applications and where a parallel
      processor can be used. For both the additive and multiplicative cases, the a
      priori mean and variance of each pixel is derived from its local mean and
      variance. Then, the minimum mean-square error estimator in its simplest form is
      applied to obtain the noise filtering algorithms. For multiplicative noise a
      statistical optimal linear approximation is made. Experimental results show that
      such an assumption yields a very effective filtering algorithm. Examples on
      images containing 256 * 256 pixels are given. Results show that in most cases the
      techniques developed in this paper are readily adaptable to real-time image
      processing.

PMID- 21868888
TI  - Model-based texture measures.
AB  - Many measures have been developed to quantify the structural properties of image
      texture. This correspondence explores their applicability to textures generated
      by several standard models.

PMID- 21868889
TI  - On the problems of constructing minimal realizations for two-dimensional filters.
AB  - The input-output behavior of a two-dimensional linear filter is defined by a
      formal power series in two variables. If the power series is rational the
      dynamics of the filter is described by updating equations on finite dimensional
      local state spaces. The class of realizations considered in this paper is
      constituted by doubly indexed dynamical systems of reduced structure. The
      construction of the class of minimal realizations is based on matrix
      representation techniques of noncommutative power series.

PMID- 21868890
TI  - The approximation of image blur restoration filters by finite impulse responses.
AB  - Image blur can often be modeled by a linear spatially invariant, symmetric point
      spread function. For this class of functions, several restoration filters are
      known in the literature. The approximation of their frequency transfer functions
      (ftf's) by the ftf's of small finite impulse response (FIR) filters has been
      studied. Accurate approximations will be possible by 9 * 9 FIR's with 8-bit
      elements if the approximation is done in a weighted MMSE sense, and if the
      truncation of the element values will be carried out such that the errors are
      small. A heuristic truncation algorithm MINIM will be described. An example of
      restoration by a 9 * 9 FIR will be shown.

PMID- 21868891
TI  - The sensitivity of the modified viterbi algorithm to the source statistics.
AB  - The modified Viterbi algorithm is a powerful, and increasingly used, tool for
      using contextual information in text recognition in its various forms. As yet, no
      known studies have been published concerning its robustness with respect to
      source statistics. This paper describes experiments performed to determine the
      sensitivity of the algorithm to variations in source statistics. The results of
      the experiments show that a character-recognition machine incorporating the
      modified Viterbi algorithm, using N-gram statistics estimated from source A does
      not deteriorate in performance when operating on a passage from source B even if
      A and B differ significantly in N-gram distributions or entropy.

PMID- 21868892
TI  - Image segmentation with directed trees.
AB  - This correspondence presents a simple algorithm to detect and label homogeneous
      areas in an image, using directed trees for region labeling. The scheme
      constructs directed trees with the image points as nodes, guided by an edge value
      computed at every point. These directed trees segment the image into disjoint
      regions. Because of a valley seeldng property of the tree construction procedure,
      the boundaries separating the resultant segments pass through the center of the
      edges. The algorithm thus performs wel1 with thick and wide edges of varying
      height, because no thresholding of the edge image is involved. The properties of
      the resultant segments are stated in terms of the edge image. The algorithm is
      shown to be simple, efficient, and effective for detecting homogeneous segments
      in the presence of noise. Results of application in the algorithm to segment a
      LANDSAT multispectral scene of an agricultural area are included.

PMID- 21868893
TI  - The Consistent Labeling Problem: Part II.
AB  - In this second part of a two-part paper, we explore the power and complexity of
      the g=fKP and g=vKP class of look-ahead operators which can be used to speed up
      the tree search in the consistent labeling problem. For a specified K and P we
      show that the fixedpoint power of g=fKP and g=vKP is the same, that g=fKP+1 is at
      least as powerful as g=fKP, and that g=vK+1p is at least as powerful at g=fKP.
      Finally, we define a minimal compatibility relation and show how the standard
      tree search procedure for finding all the consistent labelings is quicker for a
      minimal relation. This leads to the concept of grading the complexity of
      compatibility relations according to how much look-ahead work it requires to
      reduce them to minimal relations and suggests that the reason look-ahead
      operators, such as Waltz filtering, work so well is that the compatibility
      relations used in practice are not very complex and are reducible to minimal or
      near minimal relations by a g=fKP or g=vKP look-ahead operator with small value
      for parameter P.

PMID- 21868894
TI  - A theoretical comparison of texture algorithms.
AB  - An evaluation of the ability of four texture analysis algorithms to perform
      automatic texture discrimination will be described. The algorithms which will be
      examined are the spatial gray level dependence method (SGLDM), the gray level run
      length method (GLRLM), the gray level difference method (GLDM), and the power
      spectral method (PSM). The evaluation procedure employed does not depend on the
      set of features used with each algorithm or the pattern recognition scheme.
      Rather, what is examined is the amount of texturecontext information contained in
      the spatial gray level dependence matrices, the gray level run length matrices,
      the gray level difference density functions, and the power spectrum. The
      comparison will be performed in two steps. First, only Markov generated textures
      will be considered. The Markov textures employed are similar to the ones used by
      perceptual psychologist B. Julesz in his investigations of human texture
      perception. These Markov textures provide a convenient mechanism for generating
      certain example texture pairs which are important in the analysis process. In the
      second part of the analysis the results obtained by considering only Markov
      textures will be extended to all textures which can be represented by translation
      stationary random fields of order two. This generalization clearly includes a
      much broader class of textures than Markovian ones. The results obtained indicate
      that the SGLDM is the most powerful algorithm of the four considered, and that
      the GLDM is more powerful than the PSM.

PMID- 21868895
TI  - Type classification of fingerprints: a syntactic approach.
AB  - A fingerprint classification procedure using a computer is described. It
      classifies the prints into one of ten defined types. The procedure is implemented
      using PICAP (picture array processor). The picture processing system includes a
      TV camera input and a special picture processor. The first part of the procedure
      is a transformation of the original print to a sampling matrix, where the
      dominant direction of the ridges for each subpicture is indicated. After
      smoothing, the lines in this pattern are traced out and converted to strings of
      symbols. Finally, a syntactic approach is adopted to make the type classification
      based on this string of symbols.

PMID- 21868896
TI  - Segmentation of muscle cell pictures: a preliminary study.
AB  - This paper describes a procedure for segmenting muscle cell pictures. The
      segmentation procedure is broken into two logical parts. The first part segments
      the picture into regions composed of cells or clumps of cells using a number of
      low-level operations. The second part of the procedure involves the segmentation
      of the cell clumps into individual cells. This is done by using a hierarchical
      clustering algorithm to group together those boundary points of a cell clump that
      belong to the same globally convex sections of the boundary. The dissimilarity
      measure used by the clustering algorithm is based only on information about the
      shape of the boundary, where this information is derived from line segments
      interior to the boundary. This procedure has given us satisfactory results on a
      number of test pictures.

PMID- 21868897
TI  - On dimensionality, sample size, classification error, and complexity of
      classification algorithm in pattern recognition.
AB  - This paper compares four classification algorithms-discriminant functions when
      classifying individuals into two multivariate populations. The discriminant
      functions (DF's) compared are derived according to the Bayes rule for normal
      populations and differ in assumptions on the covariance matrices' structure.
      Analytical formulas for the expected probability of misclassification EPN are
      derived and show that the classification error EPN depends on the structure of a
      classification algorithm, asymptotic probability of misclassification P?, and the
      ratio of learning sample size N to dimensionality p:N/p for all linear DF's
      discussed and N2/p for quadratic DF's. The tables for learning quantity H =
      EPN/P? depending on parameters P?, N, and p for four classifilcation algorithms
      analyzed are presented and may be used for estimating the necessary learning
      sample size, detennining the optimal number of features, and choosing the type of
      the classification algorithm in the case of a limited learning sample size.

PMID- 21868898
TI  - A least mean-squared error approach to syntactic classification.
AB  - The usual approach to numerical training in syntactic pattern recognition
      involves estimation of the production probabilities of stochastic context-free
      grammars. Here we describe a different approach, namely that of finding an LMSE
      discriminant hyperplane between sets of class samples in a space of ''structural
      indices'' determined by a context-free grammar.

PMID- 21868899
TI  - Choice of kernel function for density estimation.
AB  - Let l=f^n(x) be the kernel estimate of a density f(x) from a sample of size n.
      Wahba [6] has developed an upper bound to E[f(x)-l=f^n(x)]2. In the present
      paper, we find the kernel function of finite support [m=-T, T] that minimizes
      Wahba's upper bound. It is Q(y) = (1 + am=-1) (2T)m=-1 [1-m=-a|y|a] where a = 2
      pm=-1, p m=ge 1.

PMID- 21868900
TI  - The probability distribution of conditional classification error.
AB  - The probability distribution of the error incurred by a classification system on
      a given data set is derived. It is shown that the distribution is mixed binomial.
      A method for calculating the mixed binomial distribution recursively is proposed.

PMID- 21868901
TI  - Sensitivity analysis in bayesian classification models: multiplicative
      deviations.
AB  - The sensitivity of Bayesian pattern recognition models to multiplicative
      deviations in the prior and conditional probabilities is investigated for the two
      class case. Explicit formulas are obtained for the factor K by which the computed
      posterior probabilities should be divided in order to eliminate the deviation
      effect. Numerical results for the case of binary features indicate that the
      Bayesian model tolerates large deviations in the prior and conditional
      probabilities. In fact, the a priori ratio and the likelihood ratio may deviate
      within a range of 65-135 percent and still produce posterior probabilities in
      accurate proximity of at most +/-0.10. The main implication is that Bayesian
      systems which are based on limited data or subjective probabilities are expected
      to have a high percentage of correct classification despite the fact that the
      prior and conditional probabilities they use may deviate rather significantly
      from the true values.

PMID- 21868902
TI  - Finding the extrema of a region.
AB  - The computational difficulty of finding the extreme points (those two points
      furthest from each other) in a region of an image is examined. Various approaches
      are described, including computation of convex hulls, sophisticated search
      strategies, and a statistical method. Suitability of the various methods to
      particular applications is discussed.

PMID- 21868903
TI  - High-speed multidimensional convolution.
AB  - Fast computation algorithms are developed for twodimensional and general
      multidimensional convolutions. Two basic techniques (overlap-and-add, overlap-and
      save) are described in detail. These techniques allow speed and storage
      requirement tradeoffs and they define a decomposition of the total convolution
      into partial convolutions that can be easily found by parallel use of fast
      sequential cyclic convolution algorithms. It is shown that unlike what is the
      case in one dimension, the ''overlap-and-save'' method enjoys a clear advantage
      over the ''overlap-and-add'' method with respect to speed and storage in
      multidimensional convolution. A specific computational burden is assessed for the
      case where these methods are used in conjunction with radix-2 fast Fourier
      transform algorithms.

PMID- 21868904
TI  - Bicriterion cluster analysis.
AB  - Cluster analysis is concerned with the problem of partitioning a given set of
      entities into homogeneous and well-separated subsets called clusters. The
      concepts of homogeneity and of separation can be made precise when a measure of
      dissimilarity between the entities is given. Let us define the diameter of a
      partition of the given set of entities into clusters as the maximum dissimilarity
      between any pair of entities in the same cluster and the split of a partition as
      the minimum dissimilarity between entities in different clusters. The problems of
      determining a partition into a given number of clusters with minimum diameter
      (i.e., a partition of maximum homogeneity) or with maximum split (i.e., a
      partition of maximum separation) are first considered. It is shown that the
      latter problem can be solved by the classical single-link clustering algorithm,
      while the former can be solved by a graph-theoretic algorithm involving the
      optimal coloration of a sequence of partial graphs, described in more detail in a
      previous paper. A partition into a given number of clusters will be called
      efficient if and only if there exists no partition into at most the same number
      of clusters with smaller diameter and not smaller split or with larger split and
      not larger diameter. Two efficient partitions are called equivalent if and only
      if they have the same values for the split and for the diameter.

PMID- 21868905
TI  - A nonparametric algorithm for detecting clusters using hierarchical structure.
AB  - The present paper discusses a nonparametric algorithm for detecting clusters. In
      the algorithm a positive value called potential is associated with each datum
      based on dissimilarities. By defining subordination relations among data,
      hierarchical structure is introduced into the data set. As a result of the
      introduction of hierarchical structure, the data set is divided into some subsets
      called subclusters. A procedure for constructing clusters from the subclusters is
      also considered. The proposed algorithm can be applied to a very wide range of
      data set and has great ability to detect clusters, which is verified by computer
      simulation.

PMID- 21868906
TI  - Algorithms for shape analysis of contours and waveforms.
AB  - Algorithms for shape analysis are reviewed and classified under various criteria,
      whether they examine the boundary only or the whole area and whether they
      describe the original picture in terms of scalar measurements or through
      structural descriptions. The emphasis is on methodologies which have been popular
      during the last five years and among them, those which are information
      preserving.

PMID- 21868907
TI  - The selection of critical subsets for signal, image, and scene matching.
AB  - A basic matching problem consists of locating a reference subset in a larger set
      of data subject to a given criterion. Variations of the problem include template
      matching for object recognition, matched filtering for signal detection, image
      registration, change detection, cartography feature location, correlation
      guidance, and scene matching. In the general case the data sets may be made by
      completely different sensors at different geometrical orientations. A data set in
      N dimensions can be considered as a function in N-space. The critical subset
      selection problem arises when one is given a function and must select some subset
      of the function to match with the original. In some cases uniqueness is a key
      feature of the best subset. Uniqueness may be measured by the number and relative
      magnitudes of the peaks in the cross correlation function of the original and
      subset functions. For a unique subset, another desirable characteristic is lack
      of ambiguity. This characteristic may be measured using the correlation length or
      50 percent width of the main correlation peak. The smaller the correlation
      length, the greater the certainty one has in detecting the correct match
      position. In this paper a method is presented for selecting the ''best'' subset
      of a scene where best is defined in terms of the minimum correlation length. The
      best solution is shown to be a function of the entire scene, i.e., an improper
      subset.

PMID- 21868908
TI  - Decorrelation methods of texture feature extraction.
AB  - This paper presents the development and evaluation of a visual texture feature
      extraction method based on a stochastic field model of texture. Results of recent
      visual texture discrimination experiments are reviewed in order to establish
      necessary and sufficient conditions for texture features that are in agreement
      with human discrimination. A texture feature extraction technique involving
      autocorrelation function measurement of a texture field, combined with histogram
      representation of a statistically decorrelated version of the texture field, is
      introduced. The texture feature extraction method is evaluated in terms of a
      Bhattacharyya distance measure.

PMID- 21868909
TI  - Disparity analysis of images.
AB  - An algorithm for matching images of real world scenes is presented. The matching
      is a specification of the geometrical disparity between the images and may be
      used to partially reconstruct the three-dimensional structure of the scene. Sets
      of candidate matching points are selected independently in each image. These
      points are the locations of small, distinct features which are likely to be
      detectable in both images. An initial network of possible matches between the two
      sets of candidates is constructed. Each possible match specifies a possible
      disparity of a candidate point in a selected reference image. An initial estimate
      of the probability of each possible disparity is made, based on the similarity of
      subimages surrounding the points. These estimates are iteratively improved by a
      relaxation labeling technique making use of the local continuity property of
      disparity that is a consequence of the continuity of real world surfaces. The
      algorithm is effective for binocular parallax, motion parallax, and object
      motion. It quickly converges to good estimates of disparity, which reflect the
      spatial organization of the scene.

PMID- 21868910
TI  - Random graphs: structural-contextual dichotomy.
AB  - A formal definition of random graphs is introduced which is applicable to
      graphical pattern recognition problems. The definition is used to formulate
      rigorously the structural-contextual dichotomy of random graphs. The probability
      of outcome graphs is expressed as the product of two terms, one due to the
      statistical variability of structure among the outcome graphs and the other due
      to their contextual variability. Expressions are obtained to estimate the various
      probability, typicality, and entropy measures. The members in an ensemble of
      signed digraphs are interpreted as outcome graphs of a random graph. The
      synthesized random graph is used to quantify the structural, contextual, and
      overall typicality of the outcome graphs with respect to the random graph.

PMID- 21868911
TI  - Pattern recognition as rule-guided inductive inference.
AB  - The determination of pattern recognition rules is viewed as a problem of
      inductive inference, guided by generalization rules, which control the
      generalization process, and problem knowledge rules, which represent the
      underlying semantics relevant to the recognition problem under consideration. The
      paper formulates the theoretical framework and a method for inferring general and
      optimal (according to certain criteria) descriptions of object classes from
      examples of classification or partial descriptions. The language for expressing
      the class descriptions and the guidance rules is an extension of the first-order
      predicate calculus, called variable-valued logic calculus VL21. VL21 involves
      typed variables and contains several new operators especially suited for
      conducting inductive inference, such as selector, internal disjunction, internal
      conjunction, exception, and generalization. Important aspects of the theory
      include: 1) a formulation of several kinds of generalization rules; 2) an ability
      to uniformly and adequately handle descriptors (i.e., variables, functions, and
      predicates) of different type (nominal, linear, and structured) and of different
      arity (i.e., different number of arguments); 3) an ability to generate new
      descriptors, which are derived from the initial descriptors through a rule-based
      system (i.e., an ability to conduct the so called constructive induction); 4) an
      ability to use the semantics underlying the problem under consideration. An
      experimental computer implementation of the method is briefly described and
      illustrated by an example.

PMID- 21868912
TI  - A new probabilistic relaxation scheme.
AB  - Let a vector of probabilities be associated with every node of a graph. These
      probabilities define a random variable representing the possible labels of the
      node. Probabilities at neighboring nodes are used iteratively to update the
      probabilities at a given node based on statistical relations among node labels.
      The results are compared with previous work on probabilistic relaxation labeling,
      and examples are given from the image segmentation domain. References are also
      given to applications of the new scheme in text processing.

PMID- 21868913
TI  - New methods for picture reconstruction: recursive and causal techniques.
AB  - The methods proposed by Kashyap and Mittal [1], [2] for the reconstruction of
      pictures from projections are reformulated under a regression model. These
      reinterpretations are based on least-squares and Bayesian formulations of a
      statistical linear model and lead to the derivation of recursive and causal
      algorithms which are more efficient. Experimental results with simulation of the
      filters are also presented.

PMID- 21868914
TI  - Mosaic models for textures.
AB  - This paper deals with a class of image models based on random geometric
      processes. Theoretical and empirical results on properties of patterns generated
      using these models are summarized. These properties can be used as aids in
      fitting the models to images.

PMID- 21868915
TI  - Automatic analysis of moving images.
AB  - Cine film and videotape are used to record a variety of natural processes in
      biology, medicine, meteorology, etc. This paper describes a system which detects
      and tracks moving objects from these records to obtain meaningful measures of
      their movements, such as linear and angular velocities. Features of the system
      are as follows. 1) In order to detect moving objects that are usually blurred,
      temporal differences of gray values (differences between consecutive frames) are
      used to separate moving objects from stationary objects, in addition to spatial
      differences of gray values. 2) The results of previous frames are used to guide
      feature extraction process of the next frame so that efficient processing of
      moving pictures which consists of a large number of frames is possible. 3)
      Uncertain parts in the current frame, such as occluded objects, are deduced using
      information of previous frames. 4) Misinterpreted or unknown parts in previous
      frames are reanalyzed using the results of later frames where those parts could
      be found.

PMID- 21868916
TI  - A separable median filter for image noise smoothing.
AB  - This paper investigates some properties of the separable filter resulting from
      successive applications of a one-dimensional median filter on the rows and
      columns of an image. Although the output of this separable filter is not
      identical to the corresponding nonseparable two-dimensional median filter with a
      square window, its performance in image noise smoothing is close. In particular,
      its effectiveness in smoothing noise and its behavior with edges are
      characterized and compared with those of the two-dimensional median filter. It is
      shown that the separable filter has a much simpler implementation in real-time
      hardware (at video rates, for example).

PMID- 21868917
TI  - Parallel image processing by memory-augmented cellular automata.
AB  - This paper introduces a generalization of cellular automata in which each celi is
      a tape-bounded Turing machine rather than a finite-state machine. Fast algorithms
      are given for performing various basic image processing tasks by such automata.
      It is suggested that this model of parallel computation is a very suitable one
      for studying the advantages of parallelism in this domain.

PMID- 21868918
TI  - Deduction plans: a basis for intelligent backtracking.
AB  - A proof procedure is described that relies on the construction of certain
      directed graphs called ''deduction plans.'' Plans represent the structure of
      proofs in such a way that problem reduction may be used without imposing any
      ordering on the solution of subproblems, as required by other systems. The
      structure also allows access to all clauses deduced in the course of a proof,
      which may then be used as lemmas. Economy of representation is the maximum
      attainable, consistent with this unrestricted availability of lemmas. Restricted
      versions of this deduction system correspond to existing linear deduction
      procedures, but do not suffer from some of their shortcomings, such as redundant
      representation, strict ordering of subproblems, and explicit substitution. One of
      the rules for constructing plans, however, allows a subproblem to be factored to
      a previously solved one: this has no equivalent in existing system. A further
      economy is obtained by making it unnecessary to perform substitutions and
      calculate most general unifiers. The source of unification failure can be located
      when a subproblem is found to be unsolvable, so that exact backtracking can be
      performed rather than the blind backtracking performed by existing systems.
      Therefore, a deduction system based on the construction of plans can avoid the
      wasteful search of irrelevant areas of the search space that results from the
      usual backtracking methods.

PMID- 21868919
TI  - A clustering performance measure based on fuzzy set decomposition.
AB  - Clustering is primarily used to uncover the true underlying structure of a given
      data set and, for this purpose, it is desirable to subject the same data to
      several different clustering algorithms. This paper attempts to put an order on
      the various partitions of a data set obtained from different clustering
      algorithms. The goodness of each partition is expressed by means of a performance
      measure based on a fuzzy set decomposition of the data set under consideration.
      Several experiments reported in here show that the proposed performance measure
      puts an order on different partitions of the same data which is consistent with
      the error rate of a classifier designed on the basis of the obtained cluster
      labelings.

PMID- 21868920
TI  - On the inequality of cover and hart in nearest neighbor discrimination.
AB  - When (X1, ?1),..., (Xn, ?n) are independent identically distributed random
      vectors from IRd X {0, 1} distributed as (X, ?), and when ? is estimated by its
      nearest neighbor estimate ?(1), then Cover and Hart have shown that P{?(1) ? ?}n
      ? ? ? 2E {? (X) (1 - ?(X))} ? 2R*(1 - R*) where R* is the Bayes probability of
      error and ?(x) = P{? = 1 | X = x}. They have conditions on the distribution of
      (X, ?). We give two proofs, one due to Stone and a short original one, of the
      same result for all distributions of (X, ?). If ties are carefully taken care of,
      we also show that P{?(1) ? ?|X1, ?1, ..., Xn, ?n} converges in probability to a
      constant for all distributions of (X, ?), thereby strengthening results of Wagner
      and Fritz.

PMID- 21868921
TI  - Blob detection by relaxation.
AB  - A blob is a compact region lighter (or darker) than its background surrounded by
      a smoothly curved edge. Blobs can be detected using cooperating relaxation
      processes to enhance their interior and edge probabilities. A discussion of the
      processes working independently and together is given. The use of a pyramidal
      relaxation structure, the use of the closedness of contours as an additional
      information source, and the extension of cooperating relaxation processes to a
      time sequence of images are also discussed.

PMID- 21868922
TI  - An algorithm for converting rasters to quadtrees.
AB  - An algorithm is presented for constructing a quadtree for a binary image given
      its row-by-row description. The algorithm processes the image one row at a time
      and merges identically colored sons as soon as possible, so that a minimal size
      quadtree exists after processing each pixel. This method is spacewise superior to
      one which reads in an entire array and then attempts to build the quadtree.

PMID- 21868923
TI  - An interactive image processing system.
AB  - A multiuser multiprocessing image processing system has been developed. It is an
      interactive picture manipulation and enhancement facility which is capable of
      executing a variety of image processing operations while simultaneously
      controlling real-time input and output of pictures. It was designed to provide a
      reliable picture processing system which would be cost-effective in the
      commercial production environment. Additional goals met by the system include
      flexibility and ease of operation and modification.

PMID- 21868924
TI  - The Max Roberts Operator is a Hueckel-Type Edge Detector.
AB  - Hueckel's edge detector finds the best-fitting ideal step edge to a given picture
      neighborhood by expanding the neighborhood and step edge in terms of a set of
      nine basis functions. A very simple case of this approach uses a 2 * 2
      neighborhood and three basis functions. This case is solved explicitly using
      elementary methods. The magnitude of the best-fitting step edge for the
      neighborhood AB CD turns out to be the Roberts operator max (|A - D|, |B - C|).

PMID- 21868925
TI  - Finding edges in noisy scenes.
AB  - Edge detection in the presence of noise is a well-known problem. This paper
      examines an applications-motivated approach for solving the problem using novel
      techniques and presents a method developed by the authors that performs well on a
      large class of targets. ROC curves are used to compare this method with other
      well-known edge detection operators, with favorable results. A theoretical
      argument is presented that favors LMMSE filtering over median filtering in
      extremely noisy scenes. Simulated results of the research are presented.

PMID- 21868926
TI  - Continuous relaxation and local maxima selection: conditions for equivalence.
AB  - Relaxation labeling processes are a class of iterative algorithms for using
      contextual information to reduce local ambiguities. This paper introduces a new
      perspective toward relaxation-that of considering it as a process for reordering
      labels attached to nodes in a graph. This new perspective is used to establish
      the formal equivalence between relaxation and another widely used algorithm,
      local maxima selection. The equivalence specifies conditions under which a family
      of cooperative relaxation algorithms, which generalize the well-known ones,
      decompose into purely local ones. Since these conditions are also sufficient for
      guaranteeing the convergence of relaxation processes, they serve as stopping
      criteria. We feel that equivalences such as these are necessary for the proper
      application of relaxation and maxima selection in complex speech and vision
      understanding systems.

PMID- 21868927
TI  - Pattern Recognition via Observation Correlations.
AB  - In some pattern recognition tasks multiple observations of an observation vector
      Y = {Y1, Y2, ..., YM} are available for each object and the covariances of the Yi
      are characteristic of the object. With the assistance of a model of the
      generating process for Y a theoretical basis for the comparison of the covariance
      matrices is developed. Measurements based on synthetic data support the theory,
      and an application to some speaker verification is given as an example.

PMID- 21868928
TI  - From local maxima to connected skeletons.
AB  - In picture processing it is often convenient to deal with a stick-like version
      (skeleton) of binary digital images. Although skeleton connectedness is not
      necessary for storage and retrieval purposes, this property is desirable when a
      structural description of images is of interest. In this paper a parallel
      procedure is described which, applied to a connected image, originates a
      connected skeleton made by the union of simple digital arcs. The procedure
      involves a step by step propagation of the background over the image. At every
      step, contour elements either belonging to the significant convex regions of the
      current image or being local maxima of the original image are selected as
      skeleton elements. Since the final set so obtained is not ensured to be
      connected, the configurations in correspondence of which disconnections appear
      are investigated and the procedures to avoid this shortcoming are given. The
      presence of the whole set of local maxima among the skeleton elements ensures the
      possibility of recovering the original image by means of a reverse distance
      transform. The details of the program implementing the proposed algorithm on a
      parallel processor are finally included.

PMID- 21868929
TI  - Global Shape Analysis by k-Syntactic Similarity.
AB  - The k-syntactic similarity approach is couched in graphical representation terms
      and its ability to provide global recognition capability while retaining a low
      time complexity is explored. One potential application domain, that of composite
      shape decomposition into approximately convex subshapes, is described. This is
      shown to be equivalent to finding cycles within a particular graph. The approach
      yields valid decompositions in many cases of interest, and is capable of
      identifying those cases where additional semantic considerations are necessary
      for proper analysis. The permissible graph structures representing composite
      shapes given a reasonable set of relations are determined. Experimental results
      on nonideal data are given.

PMID- 21868930
TI  - Statistical pattern classification with binary variables.
AB  - Binary random variables are regarded as random vectors in a binary-field (modulo
      2) linear vector space. A characteristic function is defined and related results
      derived using this formulation. Minimax estimation of probability distributions
      using an entropy criterion is investigated, which leads to an A-distribution and
      bilinear discriminant functions. Nonparametric classification approaches using
      Hamming distances and their asymptotic properties are discussed. Experimental
      results are presented.

PMID- 21868931
TI  - An approximate solution to normal mixture identification with application to
      unsupervised pattern classification.
AB  - In this paper, an approach to unsupervised pattern classifiation is discussed.
      The classification scheme is based on an approximation of the probability
      densities of each class under the assumption that the input patterns are of a
      normal mixture. The proposed technique for identifying the mixture does not
      require prior information. The description of the mixture in terms of convexity
      allows to determine, from a totally unlabeled set of samples, the number of
      components and, for each of them, approximate values of the mean vector, the
      covariance matrix, and the a priori probability. Discriminant functions can then
      be constructed. Computer simulations show that the procedure yields decision
      rules whose performances remain close to the optimum Bayes minimum error-rate,
      while involving only a small amount of computation.

PMID- 21868932
TI  - On the performance of chain codes for quantization of line drawings.
AB  - A class of quantization schemes is presented which generalizes various existing
      chain coding methods. For the general case, simple expressions are derived for
      the probabilities of the directional elements from which we can determine the
      number of curve points and the length of the quantized curve. These results allow
      for the comparison of performance of the various encoding schemes.

PMID- 21868933
TI  - Hough transform from the radon transform.
AB  - An appropriate special case of a transform developed by J. Radon in 1917 is shown
      to have the major properties of the Hough transform which is useful for finding
      line segments in digital pictures. Such an observation may be useful in further
      efforts to generalize the Hough transform. Techniques for applying the Radon
      transform to lines and pixels are developed through examples, and the appropriate
      generalization to arbitrary curves is discussed.

PMID- 21868934
TI  - Pixel labeling by supervised probabilistic relaxation.
AB  - A simple modification to existing probabilistic relaxation procedures is
      suggested which allows the information contained in initial labels to exert an
      influence on the direction of relaxation throughout the process. In this manner,
      the initial labels assume more importance than with conventional algorithms and
      are used in combination with the outcome of relaxation at each iteration to
      produce a cooperative estimate of the correct label for a particular object.
      Pixel labeling examples are presented which show the performance that can be
      obtained with the modified algorithm. The procedure is readily generalized to
      allow other data to influence the process.

PMID- 21868935
TI  - A new heuristic for inferring regular grammars.
AB  - Modifications to a grammatical inference scheme by Feldman et al. are presented.
      A comparison of the relative performance of the original and modified schemes is
      made using the complexity measures of Feldman and Wharton. The case where a
      complex model is used to generate the sample set is then analyzed. A set of 104
      samples was found that trained the program to infer the grammar that corresponded
      to the original model. The results of a study of the performance of this
      algorithm when there is a large number of samples is then presented. The major
      conclusion of this study is that the modified scheme has a superior performance
      on small sample sets but is highly unsuitable for large ones.

PMID- 21868936
TI  - Hierarchical representation of three-dimensional objects using verbal models.
AB  - We present a formalism for the computer representation of three-dimensional
      shapes, that has as its goal to facilitate man-machine communication using
      verbal, graphic, and visual means. With this method, pieces may be assembled
      hierarchically using any of severalways of specifying attachment. The primitives
      of the representation are generalized cylinders, and the creating of assemblies
      may make use of the axes inherent in the primitives. Generic models may be
      described that may leave some parameters or dimensions unspecified, so that when
      a specific instance of the model is described, those parameters may either be
      explicitly specified or take on default values. The axes of local coordinate
      frames may be given symbolic names. A set of computer programs translates
      descriptions of objects into polyhedral models and line drawings.

PMID- 21868937
TI  - Equivalence and reduction of expansive tree grammars.
AB  - The equivalence of nonterminals of an expansive tree grammar is considered.
      Algorithms are presented for constructing sets of equivalent nonterminals for an
      expansive tree grammar, for reducing the grammar, and for determining whether two
      grammars generate the same language.

PMID- 21868938
TI  - Pattern recognition in image processing using interpixel correlation.
AB  - When within-object interpixel correlation varies appreciably from object to
      object, it may be important for the classifier to utilize this correlation, as
      well as the mean and variance of pixel intensities. In this correspondence
      interpixel correlation is brought into the classification scheme by means of a
      two-dimensional Markov model.

PMID- 21868939
TI  - A min-max medial axis transformation.
AB  - Blum's medial axis transformation (MAT) of the set S of 1's in a binary picture
      can be defined by an iterative shrinking and reexpanding process which detects
      ''corners'' on the contours of constant distance from S?, and thereby yields a
      ''skeleton'' of S. For unsegmented (gray level) pictures, one can use an
      analogous definition, in which local MIN and MAX operations play the roles of
      shrinking and expanding, to compute a ''MMMAT value'' at each point of the
      picture. The set of points having high values defines a good ''skeleton'' for the
      set of high-gray level points in the given picture.

PMID- 21868940
TI  - Construction of a distributed associative memory on the basis of bayes
      discriminant rule.
AB  - The purpose of this correspondence is to propose a new construction method of
      distributed associative memory which operates with discrete-valued signals. In
      this method, memorized pairs of vectors (cue vectors and data vectors) are
      recorded in the form of a matrix W and a vector T. From an input vector X, the
      data vector is recalled by an operation u(XW + T) where X is a cue vector or a
      noisy cue vector. and u is a quantizing function. The methods of memorization and
      recall are similar to the Associatron; however, the proposed model can recall the
      data vectors optimally in Bayesian sense even when noisy cue vectors are given as
      the input vectors.

PMID- 21868941
TI  - An empirical evaluation of generalized cooccurrence matrices.
AB  - A comparative study of generalized cooccurrence texture analysis tools is
      presented. A generalized cooccurrence matrix (GCM) reflects the shape, size, and
      spatial arrangement of texture features. The particular texture features
      considered in this paper are 1) pixel-intensity, for which generalized
      cooccurrence reduces to traditional cooccurrence; 2) edge-pixel; and 3) extended
      edges. Three experiments are discussed-the first based on a nearest neighbor
      classifier, the second on a linear discriminant classifier, and the third on the
      Battacharyya distance figure of merit.

PMID- 21868942
TI  - Data compression of the kanji character patterns digitized on the hexagonal mesh.
AB  - This correspondence describes new two-stage data compression algorithms of Kanji
      character patterns digitized on the hexagonal mesh. One third of the pattern
      elements are stored, and an additional small amount of data is used to correct
      effors in the recovered pattern. A data reduction of 60 percent has been
      achieved.

PMID- 21868943
TI  - CCD Implementation of a Three-Dimensional Video-Tracking Algorithm.
AB  - Implementation of a three-dimensional video tracking algorithm using CCD's is
      presented. The algorithm does not require conventional pattern recognition or
      continuous segmentation updating. The only requirements, for the class of targets
      presented, are that the sampling lattice contain only points inside the target
      and that the background vary slowly. Several well-known segmentation techniques
      are available for initial segmentation and determination of target points. The
      use of CCD devices simplifies the architecture of the processor and permits real
      time processing at a high sampling rate. Some of the vector and matrix operations
      require either the use of continuously variable tapweight transversal filters or
      analog multipliers. The use of analog multipliers, which can be on-chip, reduces
      the number of components and offers higher accuracy than presently available
      variable tap weight transversal filters.

PMID- 21868944
TI  - Radial and angular moment invariants for image identification.
AB  - Radial and angular moments of images are presented and methods are shown for
      deriving moment functions that are invariant with respect to rotation,
      translation, reflection, and size changes without the aid of the theory of
      algebraic invariants. Hu's invariants are expressed in terms of these radial and
      angular moments and it is claimed that this facilitates visual inspection of
      invariance properties.

PMID- 21868945
TI  - Algorithms for detecting m-dimensional objects in N-dimensional spaces.
AB  - Exact and approximate algorithms for detecting lines in a two-dimensional image
      space are discussed. For the case of uniformly distributed noise within an image
      space, transform methods and different notions of probability measures governing
      the parameters of the transforms are described. It is shown that different
      quantization schemes of the transformed space are desirable for different
      probabilistic assumptions. The quantization schemes are evaluated and compared.
      For one of the procedures that uses a generalized Duda-Hart procedure and a mixed
      quantization scheme, the time complexity to find all m-flats in n-space is shown
      to be bounded by O(ptm(n-m)2), where p is the number of points and t is a user
      parameter. For this procedure more true flats in a given orientation have been
      found and the number of spurious flats is small.

PMID- 21868946
TI  - A pyramidal representation of images and its feature extraction facility.
AB  - This paper concerns a pyramidal representation of images. The objective of this
      study is to represent an image with as small a number of data words as possible
      in a memory without distorting the feature extraction facility inherent in
      pyramidal representations. First, a novel scheme for simplifying pyramidal
      representations is presented. Simplification is essentially based on the
      reduction of the number of informative elements observed in a window space during
      the hierarchical process of image representation. Following a brief explanation
      of the window pattern simplification process is a description of an overall
      procedure for simplifying complex binary images. Finally, for images which are
      not necessarily binary, procedure for rapid access to and selective use of
      particular areas and local control of detailed fineness are discussed in
      conjunction with the architectural considerations for implementing the system.

PMID- 21868947
TI  - Hierarchical constraint processes for shape analysis.
AB  - A major application of syntactic pattern recognition is the analysis of two
      dimensional shape. This paper describes a new syntactic shape analysis technique
      which combines the constraint propagation techniques which have been so
      successful in computer vision with the syntactic representation techniques which
      have been successfully applied to a wide variety of shape analysis problems.
      Shapes are modeled by stratified shape grammars. These grammars are designed so
      that local constraints can be compiled from the grammar describing the appearance
      of pieces of shape at various levels of description. Applications to the analysis
      of airplane shapes are presented.

PMID- 21868948
TI  - A differential operator technique for restoring degraded signals and images.
AB  - A technique is described for restoring signals, images, and other physical
      quantities that have been distorted or degraded by an imperfect measurement
      system. This technique is based upon the application of a specific differential
      operator to the measured quantity. For digital implementation, its advantages
      compared to other restoration techniques are simplicity, computational
      efficiency, and reduced core memory requirements. Calculations for a one
      dimensional example indicate that restorations comparable in quality to Wiener
      filter restorations are obtained with better than an order of magnitude decrease
      in computation time.

PMID- 21868949
TI  - Derivatives of tree sets with applications to grammatical inference.
AB  - Tree automata generalize the notion of a finite automaton working on strings to
      that of a finite automaton operating on trees. Most results for finite automata
      have been extended to tree automata. In this paper we introduce tree derivatives
      which extend the concept of Brzozowski's string derivatives. We use tree
      derivatives for minimizing and characterizing tree automata. Tree derivatives are
      used as a basis of inference of tree automata from finite samples of trees. Our
      method compares tree derivative sets and infers a tree automaton based on the
      amount of overlap between the derivative sets. Several of the limitations present
      in the tree inference techniques by Brayer and Fu and Edwards, Gonzalez, and
      Thomason are not imposed by our algorithm.

PMID- 21868950
TI  - Bayesian and decision tree approaches for pattern recognition including feature
      measurement costs.
AB  - The minimum cost classifier when general cost functions are associated with the
      tasks of feature measurement and classification is formulated as a decision graph
      which does not reject class labels at intermediate stages. Noting its
      complexities, a heuristic procedure to simplify this scheme to a binary decision
      tree is presented. The optimization of the binary tree in this context is carried
      out using dynamic programming. This technique is applied to the voiced-unvoiced
      silence classification in speech processing.

PMID- 21868951
TI  - Image approximation by variable knot bicubic splines.
AB  - This paper presents a degree of freedom or information content analysis of images
      in the context of digital image processing. As such it represents an attempt to
      quantify the number of truly independent samples one gathers with imaging
      devices. The degrees of freedom of a sampled image itself are developed as an
      approximation problem. Here, bicubic splines with variable knots are employed in
      an attempt to answer the question as to what extent images are finitely
      representable in the context of digital sensors and computers. Relatively simple
      algorithms for good knot placement are given and result in spline approximations
      that achieve significant parameter reductions at acceptable error levels. The
      knots themselves are shown to be useful as an indicator of image activity and
      have potential as an image segmentation device, as well as easy implementation in
      CCD signal processing and focal plane smart sensor arrays. Both mathematical and
      experimental results are presented.

PMID- 21868952
TI  - Three-dimensional shape analysis using local shape descriptors.
AB  - The three-dimensional shape analysis problem is a very demanding test of shape
      analysis algorithms. Previous approaches to the problem have employed global
      features such as moments and Fourier descriptors. Global features lack the
      capacity for solving the partial shape recognition problem, in which only part of
      the unknown shape is available. Previous approaches to local shape analysis have
      employed structural (syntactic) methods, but these methods have so far failed to
      solve the three-dimensional problem. This paper describes a hybrid
      structural/statistical local shape analysis algorithm which is applied to the
      three-dimensional problem.

PMID- 21868953
TI  - A three-dimensional edge operator.
AB  - Modern scanning techniques, such as computed tomography, have begun to produce
      true three-dimensional imagery of internal structures. The first stage in finding
      structure in these images, like that for standard two-dimensional images, is to
      evaluate a local edge operator over the image. If an edge segment in two
      dimensions is modeled as an oriented unit line segment that separates unit
      squares (i.e., pixels) of different intensities, then a three-dimensional edge
      segment is an oriented unit plane that separates unit volumes (i.e., voxels) of
      different intensities. In this correspondence we derive an operator that finds
      the best oriented plane at each point in the image. This operator, which is based
      directly on the 3-D problem, complements other approaches that are either
      interactive or heuristic extensions of 2-D techniques.

PMID- 21868954
TI  - Parallel computation of contour properties.
AB  - Some contour properties can be derived in parallel by a string or cycle of
      automata in linear time, faster than can be done with a single processor. In
      particular, the intersection points of two contours, the straightness of a line,
      the union or intersection of two contours, and polygonal approximations of a
      contour are computed in linear time.

PMID- 21868955
TI  - Evaluation of image fidelity by means of the fidelogram and level mean-square
      error.
AB  - In the present correspondence a method for the representa-tion of image fidelity
      is proposed and demonstrated by experimental examples. A fidelity measure is also
      proposed, which is a formal exten-sion of the commonly utilized mean-square
      error. The characteristics of these fidelity representations are discussed. As a
      result, it is shown that the representations proposed here are effective, in the
      sense that they can display clearly the level variance and average levels of the
      processed image for the standard one, or make it possible to evaluate image
      fidelity from definite aspects, as compared to existing fidelity representations.

PMID- 21868956
TI  - Reliable indexing using unreliable recognition devices.
AB  - A new method is described and tested for using an unreliable character
      recognition device to produce a reliable index for a collection of documents. All
      highly likely substitution errors of the recognition device are handled by
      transforming characters which confuse readily into the same pseudocharacter. An
      analysis of the method is done showing the expected precision (fraction of words
      correctly found to words present) and recall (fraction of words retrieved
      properly to those which were retrieved). Published substitution error matrices
      were employed, along with a large file of words and word frequencies to evaluate
      the method. Performance was surprisingly good. Suggestions for further
      enhancements are given.

PMID- 21868957
TI  - Representing and processing grammatical modifiers.
AB  - Representing English adjectives and adverbs in a logically perspicuous notation
      (extended semantic networks [17]) and their computational accommodation for
      natural language comprehension within a state-based paradigm [4] are discussed
      herewith. Where appropriate, explicit comparisons are made between this
      representational method and other related approaches such as those in [2], [9],
      [11], [12], [15], [16], [18].

PMID- 21868958
TI  - Shape segmentation using relaxation.
AB  - Relaxation is applied to the segmentation of closed boundary curves of shapes.
      The ambiguous segmentation of the boundary is represented by a directed graph
      structure whose nodes represent segments, where two nodes are joined by an arc if
      the segments are consecutive along the boundary. A probability vector is
      associated with each node; each component of this vector provides an estimate of
      the probability that the corresponding segment is a particular part of the
      object. Relaxation is used to eliminate impossible sequences of parts, or reduce
      the probabilities of unlikely ones. In experiments involving airplane shapes,
      this almost always results in a drastic simplification of the graph with only
      good interpretations surviving. The approach is also extended to include curve
      linking and gap filling. A chain coded input image is broken into segments based
      on a measure of local curvature. Gap completions linking pairs of segments are
      then proposed and represented in a graph structure. A second graph, whose nodes
      consist of paths in the above graph, is constructed, and the nodes of the second
      graph are probabilistically classified as various object parts. Relaxation is
      then applied to increase the probability of mutually supporting classifications,
      and decrease the probability of unsupported decisions. A modified relaxation
      process using information about the size, spatial position, and orientation of
      the object parts yielded a high degree of disambiguation.

PMID- 21868959
TI  - Steps toward knowledge-based machine translation.
AB  - This paper considers the possibilities for knowledge-based automatic text
      translation in the light of recent advances in artificial intelligence. It is
      argued that competent translation requires some reasonable depth of understanding
      of the source text, and, in particular, access to detailed contextual
      information. The following machine translation paradigm is proposed. First, the
      source text is analyzed and mapped into a language-free conceptual
      representation. Inference mechanisms then apply contextual world knowledge to
      augment the representation in various ways, adding information about items that
      were only implicit in the input text. Finally, a natural-language generator maps
      appropriate sections of the language-free representation into the target
      language. We discuss several difficult translation problems from this viewpoint
      with examples of English-to-Spanish and English-to-Russian translations; and
      illustrate possible solutions as embodied in a computer understander called SAM,
      which reads certain kinds of newspaper stories, then summarizes or paraphrases
      them in a variety of languages.

PMID- 21868960
TI  - A comparison of the stability characteristics of some graph theoretic clustering
      methods.
AB  - Assessing the stability of a clustering method involves the measurement of the
      extent to which the generated clusters are affected by perturbations in the input
      data. A measure which specifies the disturbance in a set of clusters as the
      minimum number of operations required to restore the set of modified clusters to
      the original ones is adopted. A number of well-known graph theoretic clustering
      methods are compared in terms of their stability as determined by this measure.
      Specifically, it is shown that among the clustering methods in any of several
      families of graph theoretic methods, clusters defined as the connected components
      are the most stable and the clusters specified as the maximal complete subgraphs
      are the least stable. Furthermore, as one proceeds from the method producing the
      most narrow clusters (maximal complete subgraphs) to those producing relatively
      broader clusters, the clustering process is shown to remain at least as stable as
      any method in the previous stages. Finally, the lower and the upper bounds for
      the measure of stability, when clusters are defined as the connected components,
      are derived.

PMID- 21868961
TI  - A locally adaptive peano scanning algorithm.
AB  - This paper describes an algorithm which builds a ''Peano scanning,'' i.e., the
      reciprocal mapping, from [0, 1]n to [0, 1], of the well-known ''Peano curve.''
      This Peano scanning is applied to a set of points in [0, 1]n and gives a one
      dimensional image of it. Several applications of this technique have already been
      developed and are presented in this paper.

PMID- 21868962
TI  - Improving consistency and reducing ambiguity in stochastic labeling: an
      optimization approach.
AB  - We approach the problem of labeling a set of objects from a quantitative
      standpoint. We define a world model in terms of transition probabilities and
      propose a definition of a class of global criteria that combine both ambiguity
      and consistency. A projected gradient algorithm is developed to minimize the
      criterion. We show that the minimization procedure can be implemented in a highly
      parallel manner. Results are shown on several examples and comparisons are made
      with relaxation labeling techniques.

PMID- 21868963
TI  - On generalized distance transformation of digitized pictures.
AB  - In this paper, we present a generalization of the distance transformation of a
      digitized picture in two different aspects. First, we define the generalized
      distance transformation of a binary picture (GDTB). A subclass of GDTB, called a
      local minimum filter family of GDTB (LMF-GDTB), characterized by a series of
      local minimum filters with varying neighborhoods, is discussed in detail. A
      skeleton is defined for LMF-GDTB, and it is proved that any binary picture can be
      reconstructed exactly from its skeleton with the distance value on it. Second,
      the gray weighted distance transformation (GWDT) is extended to a generalized
      GWDT (GGWDT) by introducing an arbitrary initial picture. After the fundamental
      equation of GGWDT and its solution are derived, it is proved that an arbitrary
      gray picture is generated by iterative application of GGWDT from a uniquely
      determined elementary picture and a sequence of initial value pictures.

PMID- 21868964
TI  - Some mathematical and representational aspects of solid modeling.
AB  - An approach is presented to the tripartite problem of modeling physical solids
      mathematically, representing the models in a computer, and using representations
      in geometric algorithms. Examples are primarily from the domain of manufacturing
      and design of discrete goods, but the results reported here have wider
      significance. Mathematical definitions can formalize many of our intuitions about
      three-dimensional (3-D) objects and operations on them. Representation-free
      (mathematical) models and functions allow formal properties to be defined for
      characterizing geometric representations. Three common representation schemes for
      3-D objects are described briefly, along with some of their formal and informal
      properties. A rigorous, as opposed to ad hoc, approach to modeling has several
      advantages. Broadly, the conceptual complications and ambiguities which are
      endemic to ad hoc problem statements and solutions may be avoided by appealing to
      a precise mathematical semantics. Mathematical rigor is mandatory in applications
      such as automatic manufacturing in which correctness must be guaranteed and
      consistency and validity maintained.

PMID- 21868965
TI  - On the influence of sample set structure on decision rule quality for the case of
      a linear discriminant function.
AB  - The influence of sample set structure on decision rule quality for the case of a
      linear discriminant function is considered. Specifically, the case of missing
      data in the sample set and the case when the multivariate random variable is to
      be registered with the help of a single-channel device are investigated. Some
      rather unusual phenomena are discussed, such as when some new samples are added
      to the sample set, and as a result the quality of parameter estimations used in a
      decision rule become better, but at the same time the quality of the decision
      rule itself becomes worse. The investigation is performed for the classical model
      of a twocategory classifier when the categories are described by the multivariate
      normal densities having common covariance matrices. Some results of statistical
      simulation experiments are included.

PMID- 21868966
TI  - Relaxation: evaluation and applications.
AB  - Probabilistic relaxation labeling processes are iterative parallel schemes that
      use contextual information to reduce local ambiguities. The behavior of these
      processes can be described by examining the rates of change and entropies of the
      probability vectors at each iteration. Examples are given comparing three
      relaxation processes as applied to several basic image analysis tasks.

PMID- 21868967
TI  - ANDAL: A Nonparametric Discrimination And Learning Algorithm for Recognition in
      Imperfectly Supervised Environments.
AB  - The problem of recognition in nonparametric environments under imperfect
      supervision is not amenable to solution through classical statistical approaches
      based on identification of finite mixtures, which require an a priori knowledge
      of the probabilistic descriptions of the classes. Accordingly, the problem is
      viewed in this study as one of optimal linear/nonlinear partitioning of the
      imperfectly labeled training sample set. This optimal partitioning is
      accomplished by defining an appropriate optimality criterion, which takes into
      account the imperfectness of supervision, and solving the resultant optimization
      problem through the Improved Flexible Polyhedron Method (IFPM). Possible
      alternatives to compensate for the inherent bias in this criterion towards
      equipopulation clusters are developed and evaluated using an illustrative
      example. Details of the methodology involved in implementing the approach are
      presented. Results of simulation experiments, which confirm the validity and
      effectiveness of this new technique in accomplishing optimal, linear/nonlinear
      discriminant learning in imperfectly supervised, nonparametric environments, are
      included.

PMID- 21868968
TI  - Some notes on cellular logic operators.
AB  - Cellular logic machines used for feature extraction in pattern recognition have
      increased in speed to the point of making it possible to execute programs
      equivalent to 1 billion general-purpose computer instructions in 1 TV frame time.
      Unfortunately, most cellular logic operators (CLO's) are designed ad hoc. It is
      important, therefore, to begin to systematize the generation of algorithms using
      CLO sequences for pattern analysis. These notes systematically analyze some
      aspects of CLO's which are used in shape discrimination and idealization and in
      object counting and sizing. New extensions of subfield numbering schemes in the
      hexagonal tessellation are introduced.

PMID- 21868969
TI  - Multidimensional edge detection by hypersurface fitting.
AB  - One way to define operators for detecting edges in digital images is to fit a
      surface (plane, quadric,...) to a neighborhood of each image point and take the
      magnitude of the gradient of the surface as an estimate of the rate of change of
      gray level in the image at that point. This approach is extended to define edge
      detectors applicable to multidimensional arrays of data-e.g., three-dimensional
      arrays obtained by reconstruction from projections-by locally fitting
      hypersurfaces to the data. The resulting operators, for hypersurfaces of degree 1
      or 2, are closely analogous to those in the two-dimensional case. Examples
      comparing some of these three-dimensional operators with their twodimensional
      counterparts are given.

PMID- 21868970
TI  - Extraction of motion information from peripheral processes.
AB  - This paper is mainly concerned with low-level processes in machine perception of
      motion. A motion analysis system should exploit information contained in ''early
      warning signals'' during the intensity based peripheral phase of motion
      perception. We show that intensity based difference pictures contain motion
      information about objects in a dynamic scene, and present methods for the
      extraction of motion information in the peripheral phase. Some experiments with
      laboratory generated and real world scenes demonstrate the potential of the
      technique.

PMID- 21868971
TI  - Structural descriptions and inexact matching.
AB  - In this paper we formally define the structural description of an object and the
      concepts of exact and inexact matching of two structural descriptions. We discuss
      the problems associated with a brute-force backtracking tree search for inexact
      matching and develop several different algorithms to make the tree search more
      efficient. We develop the formula for the expected number of nodes in the tree
      for backtracking alone and with a forward checking algorithm. Finally, we present
      experimental results showing that forward checking is the most efficient of the
      algorithms tested.

PMID- 21868972
TI  - A new method for texture fields synthesis: some applications to the study of
      human vision.
AB  - We present a general method to synthesize a stochastic process from its a priori
      given second-order statistics. Some new results, including a new conjecture
      dealing with visual discrimination of stochastic texture fields, are also given.

PMID- 21868973
TI  - Analysis of the precision of generalized chain codes for the representation of
      planar curves.
AB  - This paper examines a set of line-segment approximation codes for the
      representation of planar curves (the so-called generalized chain codes) and shows
      that the average quantization error (measure of code's precision) is directly
      proportional to the grid size and is independent of the form of the code. Thus,
      to achieve a desired level of precision for the representation of a line drawing,
      only the size of the grid need be determined; the form of the code can be chosen
      on the basis of other criteria, such as compactness, smoothness, or relative ease
      of encoding and processing.

PMID- 21868974
TI  - A modular computer vision system for picture segmentation and interpretation.
AB  - The objective of a computer vision system is to outline the objects in a picture
      and label them with an appropriate interpretation. This paper proposes a new
      paradigm for a modular computer vision system which is both data directed and
      knowledge based. The system consists of three different types of units, two of
      which are associative data memories implemented as relational databases. The
      short-term memory (STM) contains the raw color picture data and the most current
      interpretations and deductions about the original scene. The long-term memory
      (LTM) contains a detailed model of the scene under consideration. A collection of
      analysis processors, each of which is specialized for a particular task, can
      communicate with both of these memories. The information in the LTM remains
      unchanged during the analysis, while the STM is being continually updated and
      revised by the appropriate processors. The latter may be conceived of as being
      activated by certain data conditions in the STM, and using the information in
      both the LTM and STM to alter the status of the STM.

PMID- 21868975
TI  - Texture discrimination based upon an assumed stochastic texture model.
AB  - A new approach to texture discrimination is described. This approach is based
      upon an assumed stochastic model for texture in imagery and is an approximation
      to the statistically optimum maximum likelihood classifier. The construction and
      properties of the stochastic texture model are described and a digital filtering
      implementation of the resulting maximum likelihood texture discriminant is
      provided. The efficacy of this approach is demonstrated through experimental
      results obtained with simulated texture data. A comparison is provided with more
      conventional texture discriminants under identical conditions. The implications
      to texture discrimination in realworld imagery are discussed.

PMID- 21868976
TI  - Two new edge detectors.
AB  - This paper introduces two new edge detection algorithms. One uses multiple
      difference-based edge detectors. This scheme selects peak center by absolute
      maximum or center of mass techniques. The other algorithm is motivated by the
      observation that second-order enhancement improves human contour extraction, but
      generally confuses difference-based edge detectors. This algorithm translates
      intensity images into three state images (plus one, zero, and minus one), then
      uses multiple three-state edge masks to find edge positions. The second scheme
      has a multiple hardware implementation and interesting biological analogs.
      Finally, the two operators introduced are compared to some popular edge detection
      techniques from the literature.

PMID- 21868977
TI  - An optimal line following algorithm.
AB  - An algorithm is described for optimal following of the lines in digitized TV
      pictures. Initially, the picture is subjected to an edge detection operation
      resulting in short edge-line pieces (strokes). The bifurcation points of the
      lines in the picture are detected on the basis of variances in stroke angles. A
      mathematical model using graph theoretical concepts is set up on the arrays of
      strokes (streaks) to be found among the bifurcation points. The model assumes
      that the streaks will follow the lines of the picture in an optimal way. An
      algorithm is given which finds the streaks. The correctness of the algorithm is
      proved in a pure mathematical way. Experiments with on-line TV pictures show the
      performance of the algorithm.

PMID- 21868978
TI  - Thresholding using relaxation.
AB  - If a picture contains dark objects on a light background (or vice versa), the
      objects can be extracted by thresholding, i.e., by classifying the pixels into
      ''light'' and ''dark'' classes. If the picture is noisy, so that the object and
      background gray level populations overlap, there will be errors in the
      thresholded output. A relaxation process can be used to reduce these errors; we
      classify the pixels probabilistically, and then adjust the probabilities for each
      pixel, based on its neighbors' probabilities, with light reinforcing light and
      dark dark. When this adjustment process is iterated, the dark probabilities
      become very high for pixels that belong to dark regions, and vice versa, so that
      thresholding becomes trivial.

PMID- 21868979
TI  - Computer tracking of moving point targets in space.
AB  - An adaptive algorithm based on the maximum likelihood ratio is described in this
      correspondence. The algorithm detects low-intensity targets and tracks their
      paths. The charged-coupled device (CCD) mosaic sensor collects photons from the
      targets and the sky background. The algorithm computes the noise statistics,
      simulates the target pattern, correlates the received data with the target
      patterns, compares with the corresponding threshold, and prints out the positions
      and paths of the targets when present.

PMID- 21868980
TI  - On an extended fisher criterion for feature selection.
AB  - This correspondence considers the extraction of features as a task of linear
      transformation of an initial pattern space into a new space, optimal with respect
      to discriminating the data. A solution of the feature extraction problem is given
      for two multivariate normal distributed pattern classes using an extended Fisher
      criterion as the distance measure. The introduced distance measure consists of
      two terms. The first term estimates the distance between classes upon the
      difference of mean vectors of classes and the second one upon the difference of
      class covariance matrices. The proposed method is compared to some of the more
      popular alternative methods: Fukunaga-Koontz method and Foley-Sammon method.

PMID- 21868981
TI  - On the cellular convexity of complexes.
AB  - In this paper we discuss cellular convexity of complexes. A new definition of
      cellular convexity is given in terms of a geometric property. Then it is proven
      that a regular complex is celiularly convex if and only if there is a convex
      plane figure of which it is the cellular image. Hence, the definition of cellular
      convexity by Sklansky [7] is equivalent to the new definition for the case of
      regular complexes. The definition of Minsky and Papert [4] is shown to be
      equivalent to our definition. Therefore, aU definitions are virtually equivalent.
      It is shown that a regular complex is cellularly convex if and only if its
      minimum-perimeter polygon does not meet the boundary of the complex. A 0(n) time
      algorithm is presented to determine the cellular convexity of a complex when it
      resides in n * m cells and is represented by the run length code.

PMID- 21868982
TI  - Parallel region property computation by active quadtree networks.
AB  - Given a binary image stored in a cellular array, a local reconfiguration process
      can be used to reconnect some of the cells into a quadtree network representing
      the image. This quadtree can also be ''roped,'' i.e., nodes representing adjacent
      image blocks of the same size can be joined. Using the roped quadtree network as
      a parallel (cellular) computer, image properties such as perimeter and genus, as
      well as the quadtree distance transform, can be computed in O(tree height) =
      O(log image diameter) time. The area and centroid of the image can be computed in
      O(height) time without the need for roping.

PMID- 21868983
TI  - Semantic description of aerial images using stochastic labeling.
AB  - This paper discusses the application of stochastic labeling to a general symbolic
      image description problem. A method used to compute initial likelihoods and
      compatibilities is described. It was derived from an earlier symbolic matching
      procedure, but was modified to provide the data needed for application of the
      labeling method. This labeling procedure differs from simpler ones, in that it
      minimizes a global criterion at each iteration. This technique is compared to
      other matching methods, and results on two scenes are presented.

PMID- 21868984
TI  - Optimal solution of linear inequalities with applications to pattern recognition.
AB  - An algorithm for the optimal solution of consistent and inconsistent linear
      inequalities is presented, where the optimality criterion is the maximization of
      the number of constraints satisfied. In the terminology of pattern recognition,
      the algorithm finds a linear decision function which minimizes the number of
      patterns misclassified. The algorithm is developed as a nonenumerative search
      procedure based on several new results established in this paper. Bounds on the
      search are also developed and the method is experimentally evaluated and shown to
      be computationally superior to other techniques for finding minimum-error
      solutions.

PMID- 21868985
TI  - Real-time adaptive contrast enhancement.
AB  - A recursive filter approach is introduced to simplify real-time implementation of
      an adaptive contrast enhancement scheme for imaging sensors. With this scheme,
      even scenes possessing large global dynamic ranges (>40 dB) can be accommodated
      by the limited dynamic range (20 dB) of a display without losing the local
      contrast essential for image interpretation. This paper describes the recursive
      filter implementation of the local area contrast enhancement scheme using charge
      coupled devices and the resultant real-time hardware capable of processing
      standard 525 and 875 line TV compatible video (from vidicons, videotape
      recorders, etc). Several examples from video imagery are included to demonstrate
      its effectiveness.

PMID- 21868986
TI  - Determining surface orientations of specular surfaces by using the photometric
      stereo method.
AB  - The orientation of patches on the surface of an object can be determined from
      multiple images taken with different illumination, but from the same viewing
      position. The method, referred to as photometric stereo, can be implemented using
      table lookup based on numerical inversion of reflectance maps. Here we
      concentrate on objects with specularly reflecting surfaces, since these are of
      importance in industrial applications. Previous methods, intended for diffusely
      reflecting surfaces, employed point source illumination, which is quite
      unsuitable in this case. Instead, we use a distributed light source obtained by
      uneven illumination of a diffusely reflecting planar surface. Experimental
      results are shown to verify analytic expressions obtained for a method employing
      three light source distributions.

PMID- 21868987
TI  - Some results in the processing of the holy shroud of turin.
AB  - We illustrate some new developments in the three-dimensional (3-D) processing of
      the image of the Shroud of Turin. After analyzing the various possibilities of
      obtaining a ''clean'' two-dimensional (2-D) image, i.e., without noise due to
      rows and spots, we present the processed image used as a starting point for the
      three-dimensional processing. Moreover, we describe the mathematical methods used
      for the processing and show the relief image of the face. This image enhances a
      number of new details, which were not apparent on the two-dimensional image. To
      obtain a woundless natural face image of the Man of the Shroud, we processed the
      previous image suppressing the smaller and attenuating the larger wounds without
      substantially changing the features. The image shown in this article will
      probably recall the natural face of Jesus Christ. Also the processing of the body
      image is shown.

PMID- 21868988
TI  - A simple contour matching algorithm.
AB  - Two similarity measures between strings are proposed. This correspondence also
      describes an experiment performed to illustrate the inadequacy of a commonly used
      measure.

PMID- 21868989
TI  - Image smoothing based on neighbor linking.
AB  - A new method for smoothing images by local weighted averaging is presented. The
      weights are computed as strengths of links between neighbors. These link
      strengths are averages of the variations in gray level over paths of length 2. It
      is shown that the method preserves edges, thin lines, and average gray levels.
      Moreover, it transforms the images into slowly varying regions with sharp
      borders, having histograms that tend to be composed of sharp peaks.

PMID- 21868990
TI  - Computing perimeters of regions in images represented by quadtrees.
AB  - An algorithm is presented for computing the total perimeter of a region in a
      binary image represented by a quadtree. The algorithm explores each segment of
      the boundary of the region once and only once. Analysis of the algorithm shows
      that its average execution time is proportional to the number of leaf nodes in
      the quadtree.

PMID- 21868991
TI  - Image approximation from gray scale ''medial axes''.
AB  - Several types of gray-weighted ''medial axes'' have been defined. This paper
      shows that one of them, the min-max medial axis, can be used to reconstruct good
      approximations to the original image based on a relatively small amount of
      information.

PMID- 21868992
TI  - Comments on ''nosing around the neighborhood: a new system structure and
      classification rule for recognition in partially exposed environments''.
AB  - Observations are made relative to the definition and generation of a consistent
      training sample set. We show that the consistency assumption is crucial to the
      method described in the above correspondence,1 and that, in general, the proposed
      solution to the generation problem, namely k-NN editing, fails to produce
      consistent sets.

PMID- 21868993
TI  - An Efficient Two-Dimensional FFT Algorithm.
AB  - A new version of the radix-2 row-column method for computing two-dimensional fast
      Fourier transforms is proposed. It uses a ''multiple vector'' FFT algorithm to
      compute the transforms of all the columns in an array simultaneously while
      avoiding all trivial multiplications. The minicomputer implementation of the
      algorithm runs faster than the 2 * 2 vector radix FFT algorithm. Analysis of the
      numbers of complex additions and multiplications required indicate that
      implementations of the radix-4 row-column FFT and 4 * 4 vector radix FFT on the
      same minicomputer would run slower than the multiple vector implementation.

PMID- 21868994
TI  - Evaluation of projection algorithms.
AB  - A number of linear and nonlinear mapping algorithms for the projection of
      patterns from a high-dimensional space to two dimensions are available. These two
      dimensional representations allow quick visual observation of a data set. A
      combination of two popular mapping algorithms-Sammon's mean-square error
      technique and the triangulation method-is proposed to overcome the limitations in
      the individual algorithms. Some factors which describe the goodness of a
      projection are described, and a comparison is made of six of these algorithms by
      running them on four data sets. The results obtained support the use of the
      proposed algorithm.

PMID- 21868995
TI  - Elastic matching of line drawings.
AB  - Recently a dynamic elastic model [1] was proposed for automatic image matching.
      Examples were shown applying the model to dot patterns and gray scale pictures.
      This paper extends the model to line drawings. Examples are shown on handprint
      and animation, suggesting the use of dynamic matching for shape recognition and
      for motion correspondence.

PMID- 21868996
TI  - A model and tracking algorithm for a class of video targets.
AB  - Algorithms are developed for a real-time, automatic system capable of tracking
      two-dimensional (2-D) targets in complex scenes. A mathematical model of 2-D
      image spatial and temporal evolution applicable to certain classes of targets and
      target perturbations is developed. It is shown that for small target
      perturbations the 2-D tracking problem may be approximated as a 1-D time-varying
      parameter estimation problem. A CCD-implementable solution is developed which is
      particularly useful when considering target rotation and dilation and
      target/background separation. Results of system simulation and suggestions for
      future research are presented.

PMID- 21868997
TI  - Minimum cross-entropy pattern classification and cluster analysis.
AB  - This paper considers the problem of classifying an input vector of measurements
      by a nearest neighbor rule applied to a fixed set of vectors. The fixed vectors
      are sometimes called characteristic feature vectors, codewords, cluster centers,
      models, reproductions, etc. The nearest neighbor rule considered uses a non
      Euclidean information-theoretic distortion measure that is not a metric, but that
      nevertheless leads to a classification method that is optimal in a well-defined
      sense and is also computationally attractive. Furthermore, the distortion measure
      results in a simple method of computing cluster centroids. Our approach is based
      on the minimization of cross-entropy (also called discrimination information,
      directed divergence, K-L number), and can be viewed as a refinement of a general
      classification method due to Kullback. The refinement exploits special properties
      of cross-entropy that hold when the probability densities involved happen to be
      minimum cross-entropy densities. The approach is a generalization of a recently
      developed speech coding technique called speech coding by vector quantization.

PMID- 21868998
TI  - Recognition of distorted patterns using the viterbi algorithm.
AB  - In this paper a new recognition system of distorted patterns is presented, where
      the Viterbi algorithm and a modified trellis incorporating a pertinent statistics
      of distorted patterns are used. The system works in a manner quite similar to our
      own human decision process. The trellis is so constructed that it can eliminate
      all the irrelevant pattern classes at the outset and leave only the most probable
      for its fimal decision, yielding a great economy of processing time and the
      accuracy of decision. The method was applied to recognition of handwritten
      English letters and Japanese Katakana's with success. The method is also
      universal and can be applied to any category of distorted pattems.

PMID- 21868999
TI  - The use of tree derivatives and a sample support parameter for inferring tree
      systems.
AB  - Tree systems have been studied in the theoretical setting as an extension of
      finite automata. They have been found useful in the practical domain when applied
      to syntactic pattern recognition. The practical applications of tree systems have
      motivated the examination of inference techniques for tree grammars and tree
      automata. In this paper we present a tree automaton inference algorithm which
      incorporates three concepts-tree derivatives, grammatical expansion, and
      inferential strength. Tree derivatives are used for comparing tree forms.
      Grammatical expansion is a feedback mechanism which effectively enlarges the user
      sample. An inferential strength parameter is input by the user to indicate the
      amount of support required from the sample for inferences. The algorithm is also
      applied for inferring finite-state machines. Finally, we address an open problem
      posed by Joshi and Levy by demonstrating the use of our algorithm for the design
      of programming languages.

PMID- 21869000
TI  - Approximations of bayes and minimax risks and the least favorable distribution.
AB  - In this paper we present a method for approximating the risks and Bayes risk
      associated with a Bayes decision procedure. Additionally, our method leads to
      approximating the least favorable distribution and the risk associated with the
      minimax decision procedure. We assume two states of nature (or classes of
      patterns) and multivariate probability density functions. Taylor series
      expansions are used, and an nth-order polynomial equation derived from such
      expansions provides an approximation to one of the least favorable probabilities.
      An application to a normally distributed random vector of observables is
      presented with numerical comparisons. The method can be generalized to cases
      having more than two states of nature by using Taylor series expansions in
      several variables.

PMID- 21869001
TI  - Boundary detection in multidimensions.
AB  - The development of image processing algorithms for time-varying imagery and
      computerized tomography data calls for generalization of the concepts of
      adjacency, connectivity, boundary, etc., to three and four-dimensional discrete
      spaces. This paper defines these basic concepts in unified terminology and
      presents algorithms for a boundary detection task in multidimensional space. The
      performance of these algorithms is discussed with respect to theoretical maximum
      complexity, and is illustrated with simulated computerized tomography data.

PMID- 21869002
TI  - An automated approach to the design of decision tree classifiers.
AB  - The classification of large dimensional data sets arising from the merging of
      remote sensing data with more traditional forms of ancillary data causes a
      significant computational problem. Decision tree classification is a popular
      approach to the problem. This type of classifier is characterized by the property
      that samples are subjected to a sequence of decision rules before they are
      assigned to a unique class. If a decision tree classifier is well designed, the
      result in many cases is a classification scheme which is accurate, flexible, and
      computationally efficient. This correspondence provides an automated technique
      for effective decision tree design which relies only on a priori statistics. This
      procedure utilizes canonical transforms and Bayes table look-up decision rules.
      An optimal design at each node is derived based on the associated decision table.
      A procedure for computing the global probability of correct classification is
      also provided. An example is given in which class statistics obtained from an
      actual Landsat scene are used as input to the program. The resulting decision
      tree design has an associated probability of correct classification of 0.75
      compared to the theoretically optimum 0.79 probability of correct classification
      associated with a full dimensional Bayes classifier. Recommendations for future
      research are included.

PMID- 21869003
TI  - A refinement of a spherical decomposition algorithm.
AB  - A refinement is suggested to the O'Rourke-Badler spherical decomposition
      algorithm which reduces its complexity from 0(n3) to 0(n2).

PMID- 21869004
TI  - Scene-based nonuniformity compensation for imaging sensors.
AB  - Multidetector imaging focal plane arrays like CCD TV cameras and infrared arrays
      possess large detector-to-detector dark current (offset) and responsivity (gain)
      variations which can completely mask the useful information. Conventional
      compensation techniques require temperature references of constant radiance over
      the entire field of view and a mechanical/electrooptical shutter to calibrate the
      focal plane. This detracts from the mechanical simplicity of multi-detector
      staring (nonscanning) focal planes. This correspondence describes a real-time
      offset and responsivity (gain) compensation technique which dispenses with
      temperature references and shutters in staring focal planes. It makes use of the
      scene statistics for calibration and continuously updates the compensation
      coefficients without interrupting the field of view. The results of real-time
      simulations of this technique with a number of sensors are presented. Real-time
      LSI/VLSI hardware architectures are addressed. The technique can be implemented
      with the addition of very little hardware to a conventional compensation
      technique requiring temperature references. The technique is also suitable for
      multi-detector scanning focal planes and for the removal of shading in TV sensors
      as well.

PMID- 21869005
TI  - A maximum likelihood approach to texture classification.
AB  - A new approach to texture classification is described which is based on
      measurements of the spatial gray-level co-occurrence probability matrix. This
      approach can make use of assumed stochastic models for texture in imagery and is
      an approximation to the statistically optimum maximum likelihood classifier. The
      efficacy of the approach is demonstrated through experimental results obtained
      with real-world texture data.

PMID- 21869006
TI  - A core-line tracing algorithm based on maximal square moving.
AB  - This paper newly proposes and discusses a maximal square moving (MSM) algorithm
      for tracing the core lines or medial lines of objects in a digitized binary
      picture, by which structure-descriptive core-line representations are directly
      obtained. The MSM algorithm could be considered to be an extension of the medial
      axis transform (MAT) definition to discrete images since maximal squares are sub
      stituted for maximal disks, but it is, in essence, distinct from the con
      ventional methods since it is based on what is called an input-time tracing
      principle. The algorithm is fast and requires no image memory, and the
      connectivity of the core lines so derived is completely guaranteed in a sense of
      maximal square neighborhood relations. Furthermore, the original objects can be
      exactly reconstructed from their core lines derived.

PMID- 21869007
TI  - A method for selecting constrained hand-printed character shapes for machine
      recognition.
AB  - Since handwritten characters vary in shape and writing-stroke sequence, it is
      desirable to develop a standard set of characters that are of high quality, so
      that not only are they easy to write, but they are also most suitable for machine
      recognition. A database of more than 100 000 alphanumeric patterns was assembled.
      It consisted of 174 models of the alphanumeric characters written by both left
      handed and right-handed subjects. Based on frequency density and distance
      measurements, a nietric called the dispersion factor was computed to rank the
      various models. The principle of the metric is discussed, and results are given
      indicating the high quality models of the alphanumerics.

PMID- 21869008
TI  - Pixel classification based on gray level and local ''busyness''.
AB  - An image can be segmented by classifying its pixels using local properties as
      features. Two intuitively useful properties are the gray level of the pixel and
      the ''busyness,'' or gray level fluctuation, measured in its neighborhood.
      Busyness values tend to be highly vari-able in busy regions; but great
      improvements in classification accuracy can be obtained by smoothing these values
      prior to classifying. An alternative possibility is to classify probabilistically
      and use relaxation to adjust the probabilities.

PMID- 21869009
TI  - On bayes risk consistent pattern recognition procedures in a quasi-stationary
      environment.
AB  - Van Ryzin and Greblicki showed that pattern recognition procedures derived from
      orthogonal series estimates of a probability density function are Bayes risk
      consistent. In this note it is proved that these procedures do not lose-under
      some additional conditions-their asymptotic properties even if the random
      environment is nonstationary.

PMID- 21869010
TI  - Analysis of ''dot product space'' shape descriptions.
AB  - A convenient representation for blob-like figures in an image consists of the
      orientation, length, and width of a bounding rect-angle. One fast algorithm for
      producing such a bounding rectangle is based upon a dot product space. The
      analysis of the dot product space shape representation is improved to handle
      certain pathological cases, and it is shown how to generalize this analysis to
      accommodate different criteria for the goodness of the representation.

PMID- 21869011
TI  - Threshold selection using quadtrees.
AB  - A simple class of piecewise constant approximations to an image is constructed as
      follows: start with the entire image, subdivide it into quadrants if its gray
      level standard deviation is high, and repeat the process for each quadrant. This
      yields a decomposition of the image into blocks, each having low standard
      deviation, so that each of them can be approximated by a constant value, namely,
      its mean. The histogram of this approximated image tends to have sharper peaks
      than that of the original image since the block averaging reduces the variability
      of the gray levels within homogeneous regions. A possible way of further
      improving the histogram is based on the fact that small blocks tend to occur near
      region borders; thus, suppressing these blocks should tend to deepen the valleys
      on the histogram, making threshold selection (to separate regions of different
      types) easier. Conversely, the histogram of the small blocks only represents a
      population of pixels near region borders, and if there are only two types of
      regions (e.g., objects and background), the mean of this histogram should be a
      useful threshold for separating them; but in practice, this method is not very
      reliable since background fluctuations also give rise to border pixels.

PMID- 21869012
TI  - Optimal Choice of AR and MA Parts in Autoregressive Moving Average Models.
AB  - This paper deals with the Bayesian method of choosing the best model for a given
      one-dimensional series among a finite number of candidates belonging to
      autoregressive (AR), moving average (MA), ARMA, and other families. The series
      could be either a sequence of observations in time as in speech applications, or
      a sequence of pixel intensities of a two-dimensional image. The observation set
      is not restricted to be Gaussian. We first derive an optimum decision rule for
      assigning the given observation set to one of the candidate models so as to
      minimize the average probability of error in the decision. We also derive an
      optimal decision rule so as to minimize the average value of the loss function.
      Then we simplify the decision rule when the candidate models are different
      Gaussian ARMA models of different orders. We discuss the consistency of the
      optimal decision rule and compare it with the other decision rules in the
      literature for comparing dynamical models.

PMID- 21869013
TI  - Waveform feature extraction based on tauberian approximation.
AB  - A technique is presented for feature extraction of a waveform y based on its
      Tauberian approximation, that is, on the approximation of y by a linear
      combination of appropriately delayed versions of a single basis function x, i.e.,
      y(t) = ?M i = 1 aix(t - ?i), where the coefficients ai and the delays ?i are
      adjustable parameters. Considerations in the choice or design of the basis
      function x are given. The parameters ai and ?i, i=1, . . . , M, are retrieved by
      application of a suitably adapted version of Prony's method to the Fourier
      transform of the above approximation of y. A subset of the parameters ai and ?i,
      i = 1, . . . , M, is used to construct the feature vector, the value of which can
      be used in a classification algorithm. Application of this technique to the
      classification of wide bandwidth radar return signatures is presented. Computer
      simulations proved successful and are also discussed.

PMID- 21869014
TI  - Sampling considerations for multilevel crossing analysis.
AB  - This paper examines the amplitude fluctuations of band-limited functions with
      bounded zeroth absolute moments, and the problems associated with estimating the
      level crossing profiles of these functions. Level crossings have received
      increased attention as features for pattern recognition because of their
      capability to provide information related to both amplitude and frequency
      behavior. A detailed analysis of the average rate of change of band-limited
      functions is presented, including a derivation of the least upper bound on
      functions for which the zeroth absolute moments of the functions are bounded. The
      average rate of change of a function over an interval in which one endpoint of
      the interval is an extremum of the function is similarly bounded and used to
      establish a sampling rate which guarantees that between successive samples of a
      band-limited function with bounded zeroth absolute moment the function itself
      does not deviate from the amplitude interval defined by the samples by more than
      some predefined amplitude change. Based on these results, a theorem is developed
      which defines the sampling rate required to ensure that, in the estimation of
      level crossing profiles, no more than 2m (m >> 1) level crossings of m levels are
      missed per extremum of the sampled function. It is shown that the sampling rate
      defined by this theorem reduces to the well-known Nyquist rate for the special
      case of zero crossing analysis.

PMID- 21869015
TI  - ARMA Modeling of Time Series.
AB  - A method for efficiently generating a rational model of a wide-sense stationary
      time series is presented. In this method the autoregressive parameters associated
      with an ARMA model consisting of q zeros and p poles are optimally chosen with
      the selection being based on a finite set of time series observations. This
      selection is made so that a set of Yule-Walker equation approximations are
      ''best'' satisfied. The resultant autoregressive parameter estimates have the
      desired statistical feature of being unbiased and consistent. This estimation
      method has been found to provide a modeling performance which typically equals or
      exceeds that of contemporary alternatives. Moreover, this method is amenable to a
      computationally efficient adaptive solution procedure. The autoregressive
      parameters characterizing the resultant ARMA model estimate can serve the role of
      decision variables in pattern classification schemes. For example, these
      parameters can be utilized in determining whether or not a member(s) of a given
      signal class is contained within a noise corrupted measurement signal. This
      approach has been found to be particularly effective in Doppler radar and array
      processing applications in which one is looking for the presence of spectral
      lines (i.e., sinusoids) in the measurement signal.

PMID- 21869016
TI  - Adaptive and learning algorithms for seismic detection of personnel.
AB  - This correspondence is concerned with adaptive digital processing to extract
      impulse-like signal features from the correlated background noise for detection
      of intruders with the seismic sensor data. Both the adaptive digital filtering
      and the adaptive Kalman filtering methods are developed and shown to perform
      nearly the same for a short data segment. For continued processing of a long
      duration seismic record, the adaptive Kalman filtering considered has better
      capability to learn the nonstationary data characteristics than the considered
      adaptive filtering and to adaptively remove the background noise. Detailed
      experimental results are presented. Other considerations such as the hardware
      implementation and the relationships among the parameters are also examined.

PMID- 21869017
TI  - Adaptive detection and removal of non-gaussian spikes from gaussian data.
AB  - A nonlinear adaptive method is presented for filtering a signal which is
      corrupted by spikes which take discrete values Mi with probability Pi at random
      points in time. An unsupervised learning technique is used to estimate the
      unknown parameters Mi, Pi, and oi. The spikes are then removed using a Bayes
      classifier. A theoretical and experimental comparison with the MMSE linear filter
      is presented.

PMID- 21869018
TI  - A syntactic approach to seismic pattern recognition.
AB  - The nearest-neighbor decision rule for syntactic patterns is applied to seismic
      pattern classification. Each pattern is represented by a string. The string-to
      string distance is used as a similarity measure. Another method using finite
      state grammars inferred from the training samples and error-correcting parsers is
      also implemented. Both methods show equal recognition accuracy; however, the
      nearest-neighbor rule is much faster in computation speed. The classification
      results of real earthquake/explosion data are presented.

PMID- 21869019
TI  - Nonlinear restoration of noisy images.
AB  - The restoration of images degraded by an additive white noise is performed by
      nonlinearly filtering a noisy image. The standard Wiener approach to this problem
      is modified to take into account the edge information of the image. Various
      filters of increasing complexity are derived. Experimental results are shown and
      compared to the standard Wiener filter results and other earlier attempts
      involving nonstationary filters.

PMID- 21869020
TI  - Digital straight lines and convexity of digital regions.
AB  - It is shown that a digital region is convex if and only if every pair of points
      in the region is connected by a digital straight line segment contained in the
      region. The midpoint property is shown to be a necessary but not a sufficient
      condition for the convexity of digital regions. However, it is shown that a
      digital region is convex if and only if it has the median-point property.

PMID- 21869021
TI  - Any discrimination rule can have an arbitrarily bad probability of error for
      finite sample size.
AB  - Consider the basic discrimination problem based on a sample of size n drawn from
      the distribution of (X, Y) on the Borel sets of Rdx {O, 1}. If 0 < R*< is a given
      number, and 'n - 0 is an arbitrary positive sequence, then for any discrimination
      rule one can find a distribution for (X, Y), not depending upon n, with Bayes
      probability of error R* such that the probability of error (Rn) of the
      discrimination rule is larger than R* + 'On for infinitely many n. We give a
      formal proof of this result, which is a generalization of a result by Cover [1].

PMID- 21869022
TI  - A model for radar images and its application to adaptive digital filtering of
      multiplicative noise.
AB  - Standard image processing techniques which are used to enhance noncoherent
      optically produced images are not applicable to radar images due to the coherent
      nature of the radar imaging process. A model for the radar imaging process is
      derived in this paper and a method for smoothing noisy radar images is also
      presented. The imaging model shows that the radar image is corrupted by
      multiplicative noise. The model leads to the functional form of an optimum
      (minimum MSE) filter for smoothing radar images. By using locally estimated
      parameter values the filter is made adaptive so that it provides minimum MSE
      estimates inside homogeneous areas of an image while preserving the edge
      structure. It is shown that the filter can be easily implemented in the spatial
      domain and is computationally efficient. The performance of the adaptive filter
      is compared (qualitatively and quantitatively) with several standard filters
      using real and simulated radar images.

PMID- 21869023
TI  - Implementation, interpretation, and analysis of a suboptimal boundary finding
      algorithm.
AB  - This paper presents a suboptimal boundary estimation algorithm for noisy images
      which is based upon an optimal maximum likelihood problem formulation. Both the
      maximum likelihood formulation and the resulting algorithm are described in
      detail, and computational results are given. In addition, the potential power of
      the likelihood formulation is demonstrated through the presentation of three
      simple but insightful analyses of algorithm performance. These analyses are based
      on a technique we have developed for comparing the accuracies of different
      boundary finding algorithms. This technique also helps in understanding the
      interplay of object shape and data models in the relative performances of
      boundary finders. Some of the algorithm design considerations resulting from the
      use of our analysis technique are new and, at first, surprising. Our technique
      appears to be the only one developed for comparing the accuracies of different
      boundary finding algorithms.

PMID- 21869024
TI  - Description of textures by a structural analysis.
AB  - A structural analysis system for describing natural textures is introduced. The
      analyzer automatically extracts the texture elements in an input image, measures
      their properties, classifies them into some distinctive classes (one ''ground''
      class and some ''figure'' classes), and computes the distributions of the gray
      level, the shape, and the placement of the texture elements in each class. These
      descriptions are used for classification of texture images. An analysis-by
      synthesis method for evaluating texture analyzers is also presented. We propose a
      synthesizer which generates a texture image based on the descriptions. By
      comparing the reconstructed image with the original one, we can see what
      information is preserved and what is lost in the descriptions.

PMID- 21869025
TI  - Design, analysis, and implementation of a parallel tree search algorithm.
AB  - The alpha-beta algorithm for searching decision trees is adapted to allow
      parallel activity in different parts of a tree during the search. The algorithm
      has been implemented in a procedural simulation language (GASP IV). The
      simulation environment provides the illusion of multiple software processes and
      multiple hardware processors. A number of preliminary experiments have been done
      to gather statistics on run time, nodes scored, and nodes visited. Results
      indicate that a substantial reduction in time of search occurs because of the use
      of parallelism. An analytic expression for the storage requirements of the
      algorithm is derived. The analysis provides an example of the classical tradeoff
      between time and storage.

PMID- 21869026
TI  - A note on the quantitative measure of image enhancement through fuzziness.
AB  - The ''index of fuzziness'' and ''entropy'' of an image reflect a kind of
      quantitative measure of its enhancement quality. Their values are found to
      decrease with enhancement of an image when different sets of S-type membership
      functions with appropriate crossover points were considered for extracting the
      fuzzy property plane from the spatial domain of the image.

PMID- 21869027
TI  - Efficient spiral search in bounded spaces.
AB  - This correspondence defines approaches for the efficient generation of a spiral
      like search pattern within bounded rectangularly tessellated regions. The defined
      spiral-like search pattern grows outward from a given source in a two-dimensional
      space, thus tending to minimize search time in many sequential tracking tasks.
      Efficient spiral generation is achieved by minimizing the number of operations
      required for interaction with boundaries. Algorithms are developed for both
      rectangular search regions and for arbitrary convex search regions.

PMID- 21869028
TI  - Statistical properties of error estimators in performance assessment of
      recognition systems.
AB  - The problem of estimating the error probability of a given classification system
      is considered. Statistical properties of the empirical error count (C) and the
      average conditional error (R) estimators are studied. It is shown that in the
      large sample case the R estimator is unbiased and its variance is less than that
      of the C estimator. In contrast to conventional methods of Bayes error estimation
      the unbiasedness of the R estimator for a given classifier can be obtained only
      at the price of an additional set of classified samples. On small test sets the R
      estimator may be subject to a pessimistic bias caused by the averaging phenomenon
      characterizing the functioning of conditional error estimators.

PMID- 21869029
TI  - A microcomputer system for processing natural languages.
AB  - This correspondence describes a microcomputer system, called ?BE (for
      microprocessor-based English), for processing natural languages. Its techniques
      and facilities, however, should be extendible to other languages. By using the
      microprocessor as special purpose hardware for several functions of a natural
      language processor (in particular, hashing and parsing), the system aids
      computational linguists by increasing the computational power available for
      natural language investigations. An overview of ?BE is given followed by a more
      detailed discussion of the hasher and parser. The paper concludes with specific
      applications of the microprocessor system to computational linguistics. ?BE is
      not based on a particular theory of language so that the system's user may define
      his own theory and investigate its consequences. ?BE contains facilities and
      capabilities to assist such investigations.

PMID- 21869030
TI  - Matching Images to Models for Registration and Object Detection via Clustering.
AB  - A new technique is presented for matching image features to maps or models. The
      technique forms all possible pairs of image features and model features which
      match on the basis of local evidence alone. For each possible pair of matching
      features the parameters of an RST (rotation, scaling, and translation)
      transformation are derived. Clustering in the space of all possible RST parameter
      sets reveals a good global transformation which matches many image features to
      many model features. Results with a variety of data sets are presented which
      demonstrate that the technique does not require sophisticated feature detection
      and is robust with respect to changes of image orientation and content. Examples
      in both cartography and object detection are given.

PMID- 21869031
TI  - A Discrete Version of Green's Theorem.
AB  - We formulate a discrete version of Green's theorem such that a summation of a two
      dimensional function over a discrete region can be evaluated by the use of a
      summation over its discrete boundary. In many cases, the discrete Green theorem
      can result in computational gain. Applications of the discrete Green theorem to
      several typical image processing problems are demonstrated. We also apply it to
      analyze shapes of particle aggregates of Fe2O3. Experimental results of the shape
      study are presented.

PMID- 21869032
TI  - GODDESS: A Goal-Directed Decision Structuring System.
AB  - This paper describes an operational version of a computerized, domain
      independent, decision support system which is based on a novel, goal-directed
      structure for representing decision problems. The structure allows the user to
      state relations among aspects, effects, conditions, and goals, in addition to
      actions and states which are the basic components of the traditional decision
      tree approach. The program interacts with the user in a stylized English-like
      dialogue, starting with the stated objectives and proceeding to unravel the more
      detailed means by which these objectives can be realized. At any point in time,
      the program focuses the user's attention on the issues which are most crucial to
      the problem at hand. The structure used is more compatible with the way people
      encode knowledge about problems and actions, and therefore promises to offer the
      following advantages: 1) judgments and beliefs issued by the user constitute a
      more valid representation of the user's experience; and 2) the user may be guided
      toward the discovery of action alternatives he otherwise would not have
      identified.

PMID- 21869033
TI  - Studies in global and local histogram-guided relaxation algorithms.
AB  - An image segmentation algorithm based on histogram clustering and probabilistic
      relaxation labeling is explored. The algorithm is evaluated by means of a set of
      artificially generated test images with known parameters. Two sources of pixel
      labeling errors are revealed. The first derives from distribution overlap in the
      histogram and leads to fragmented or missing regions in a segmentation. The
      second derives from the gloal nature of the compatibility coefficients used in
      the relaxation process. The coefficients are shown to be insufficient to correct
      certain labeling errors and can even cause the destruction of fine image details
      during the course of the relaxation updating process. A potential solution to
      these problems is shown to be obtainable by using orientation dependent
      compatibility coefficients and localizing the scope of the algorithm to small
      subimages followed by a merging of the segmented subimages.

PMID- 21869034
TI  - Cell tracking: a modeling and minimization approach.
AB  - This paper presents a model of motion suitable for cell tracking. It includes a
      representation for cell dynamics enabling it to maintain a correspondence between
      successive images of cells undergoing morphological changes. This model is based
      on a minimization problem whose computational solution is similar in form to a
      Newton-Rhapson iteration. The model is supported by experimental results from an
      actual tracking problem.

PMID- 21869035
TI  - Systematic feature extraction.
AB  - A systematic feature extraction procedure is proposed. It is based on successive
      extractions of features. At each stage a dimensionality reduction is made and a
      new feature is extracted. A specific example is given using the Gaussian minus
      log-likelihood ratio as a basis for the extracted features. This form has the
      advantage that if both classes are Gaussianly distributed, only a single feature,
      the sufficient statistic, is extracted. If the classes are not Gaussianly
      distributed, additional features are extracted in an effort to improve the
      classification performance. Two examples are presented to demonstrate the
      performance of the procedure.

PMID- 21869036
TI  - Distance transform for images represented by quadtrees.
AB  - The concept of distance used in binary array representations of images is adapted
      to a quadtree representation. The chessboard distance metric is shown to be
      particularly suitable for the quadtree. A chessboard distance transform for a
      quadtree is defined as the minimum distance in the plane from each BLACK node to
      the border of a WHiTE node. An algorithm is presented which computes this
      transform by only examining the BLACK node's adjacent and abutting neighbors and
      their progeny. However, unlike prior work with quadtrees, computation of the
      distance transform requires a capability of finding neighbors in the diagonal
      direction rather than merely in the horizontal and vertical directions. The
      algorithm's average execution time is proportional to the number of leaf nodes in
      the quadtree.

PMID- 21869037
TI  - On the difficulties involved in the segmentation of pictures.
AB  - The problem of picture segmentation is widely believed to be practically
      unsolvable in its more general case formulation. However, as far as the authors
      know no formal argumentation has yet been given to this belief related to the
      segmentation problem. This correspondence provides some theoretical aspects of
      this phenomenon.

PMID- 21869038
TI  - A counterexample to a diameter algorithm for convex polygons.
AB  - Recently, Snyder and Tang [1] proposed an algorithm for finding the diameter of a
      convex polygon. In this note a family of convex polygons is described for which
      their algorithm fails. It is also pointed out that the diameter of an arbitrary
      simple n-vertex polygon can be computed in O(n) time.

PMID- 21869039
TI  - An empirical comparison of backtracking algorithms.
AB  - In this paper we report the results of experimental studies of zero-level, one
      level, and two-level search rearrangement backtracking. We establish upper and
      lower limits for the size problem for which one-level backtracking is preferred
      over zero-level and two-level methods, thereby showing that the zero-level method
      is best for very small problems. The one-level method is best for moderate size
      problems, and the two-level method is best for extremely large problems. Together
      with our theoretical asymptotic formulas, these measurements provide a useful
      guide for selecting the best search rearrangement method for a particular
      problem.

PMID- 21869040
TI  - Comments on ''a counterexample to a diameter algorithm for convex polygons''.

PMID- 21869041
TI  - A method for finding pairs of antiparallel straight lines.
AB  - A method of pairing antiparallel straight lines is presented and discussed. The
      pairing is based on the distance between the lines, the amount by which they
      overlap, and on whether or not other lines are interposed. Examples are shown of
      applying the method to high resolution aerial photographs. Results indicate that
      cultural features such as roads and buildings can be extracted and that a
      significant reduction in the complexity of the image description can be obtained.

PMID- 21869042
TI  - Feature extraction using problem localization.
AB  - Feature extraction is considered as a mean-quare estimation of the Bayes risk
      vector. The problem is simplified by partitioning the distribution space into
      local subregions and performing a linear estimation in each subregion. A modified
      clustering algorithm is used to fimd the partitioning which minimizes the mean
      square error.

PMID- 21869043
TI  - A gestalt-guided heuristic boundary follower for x-ray images of lung nodules.
AB  - A ''piecewise heuristic'' follower of the boundaries of difficult-to-notice
      nonoverlapping blobs in digitized images is described. The technique was tested
      on 324 X-ray images of candidate lung nodules from eight radiographs with good
      results. This technique is several times faster than earlier detectors of the
      boundaries of lung nodules, while maintaining good fidelity of the detected
      boundaries.

PMID- 21869044
TI  - Scaling binary images with the telescoping template.
AB  - The importance of enlarging and reducing two-level images such as graphical and
      documentary matter by digital means continues to grow as more such images are
      digitally represented. A nonlinear scaling scheme is devised which exploits the
      simplicity of this binary nature, treating images logically instead of
      arithmetically; a convolution-like effect is achieved without a single addition
      or multiplication! This method yields high-fidelity digital scaling and meets the
      objectives of being fast, conducive to hardware realization, and void of special
      pre-encoding requirements.

PMID- 21869045
TI  - Dot pattern processing using voronoi neighborhoods.
AB  - A sound notion of the neighborhood of a point is essential for analyzing dot
      patterns. The past work in this direction has concentrated on identifying pairs
      of points that are neighbors. Examples of such methods include those based on a
      fixed radius, k-nearest neighbors, minimal spanning tree, relative neighborhood
      graph, and the Gabriel graph. This correspondence considers the use of the region
      enclosed by a point's Voronoi polygon as its neighborhood. It is argued that the
      Voronoi polygons possess intuitively appealing characteristics, as would be
      expected from the neighborhood of a point. Geometrical characteristics of the
      Voronoi neighborhood are used as features in dot pattern processing. Procedures
      for segmentation, matching, and perceptual border extraction using the Voronoi
      neighborhood are outlined. Extensions of the Voronoi definition to other domains
      are discussed.

PMID- 21869046
TI  - Repeated hypothesis testing on a growing data set.
AB  - In many problems, especially when data are collected over a long period of time,
      hypothesis testing is done repeatedly as new data arrive. It is shown both for
      one particular problem and for a more general class of problems that if testing
      is performed each time on the total amount of data accumulated, the true simple
      null hypothesis will be rejected at least once as the number of tests approaches
      infinity. Furthermore, it is conjectured that the conclusion holds for most
      problems of interest in which the null hypothesis is simple.

PMID- 21869047
TI  - Similarity measures between strings extended to sets of strings.
AB  - Similarity measures between strings (finite-length sequences of symbols) are
      extended to apply to sets of strings in an intuitive way which also preserves
      some of the desired properties of the initial similarity measure. Two quite
      different measures are used in the examples: the first for applications where
      numerical computation of pointwise similarity is needed; the second for
      applications which depend more heavily on substring similarity. It is presumed
      throughout that alphabets may be nondenumerable; in particular, the unit interval
      [0, 1] is used as the alphabet in the examples.

PMID- 21869048
TI  - On the chain code of a line.
AB  - In 1970 Freeman suggested the following criteria which the chain code of a line
      must meet [1], [2]: 1) at most two basic directions are present and these can
      differ only by unity, modulo eight, 2) one of these values always occurs singly,
      3) successive occurrences of the principal direction occurring singly are as
      uniformly spaced as possible. In this correspondence we give the following: 1) an
      algorithm presentation of Freeman's three properties about the chain code of a
      line and the proof that it is also the algorithm recognizing whether a chain code
      is the chain code of a line, 2) the proof of the equivalence of the above
      presentation and Rosenfeld's chord property [3].

PMID- 21869049
TI  - Cluster Validity for the Fuzzy c-Means Clustering Algorithrm.
AB  - The uniform data function is a function which assigns to the output of the fuzzy
      c-means (Fc-M) or fuzzy isodata algorithm a number which measures the quality or
      validity of the clustering produced by the algorithm. For the preselected number
      of cluster c, the Fc-M algorithm produces c vectors in the space in which the
      data lie, called cluster centers, which represent points about which the data are
      concentrated. It also produces for each data point c-membership values, numbers
      between zero and one which measure the similarity of the data points to each of
      the cluster centers. It is these membership values which indicate how the point
      is classified. They also indicate how well the point has been classified, in that
      values close to one indicate that the point is close to a particular center, but
      uniformly low memberships indicate that the point has not been classified
      clearly. The uniform data functional (UDF) combines the memberships in such a way
      as to indicate how well the data have been classified and is computed as follows.
      For each data point compute the ratio of its smallest membership to its largest
      and then compute the probability that one could obtain a smaller ratio
      (indicating better classification) from a clustering of a standard data set in
      which there is no cluster structure. These probabilities are then averaged over
      the data set to obtain the values of the UDF.

PMID- 21869050
TI  - Medial axis transformation of a planar shape.
AB  - The medial axis transformation is a means first proposed by Blum to describe a
      shape. In this paper we present a 0(n log n) algorithm for computing the medial
      axis of a planar shape represented by an n-edge simple polygon. The algorithm is
      an improvement over most previously known results interms of both efficiency and
      exactness and has been implemented in Fortran. Some computer-plotted output of
      the program are also shown in the paper.

PMID- 21869051
TI  - Rule-Based Learning for More Accurate ECG Analysis.
AB  - Long-term electrocardiograms exhibit a small number of QRS morphologies (waveform
      shapes) whose analysis can reveal cardiac abnormalities. We considered the
      problem of accurately identifying instances of each in 24-h ECG recordings. A new
      learning algorithm was developed. Each QRS morphology is represented as a tree of
      rule activations, which associate attribute measurements with a rule. Each rule
      has a syntactic pattern together with a semantic procedure which manages and
      applies the knowledge stored in the activation. A single rule may be activated
      several times to learn different waveform segments. Delineation refinement
      improves each hypothesized signal interpretation. A simple conflict resolution
      mechanism resolves conflicting interpretations into a single unambiguous one.
      Comparison of the system with an existing program confirmed the promise of the
      new approach.

PMID- 21869052
TI  - Unsupervised learning approach to adaptive differential pulse code modulation.
AB  - This research is concerned with investigating the problem of data compression
      utilizing an unsupervised estimation algorithm. This extends previous work
      utilizing a hybrid source coder which combines an orthogonal transformation with
      differential pulse code modulation (DPCM). The data compression is achieved in
      the DPCM loop, and it is the quantizer of this scheme which is approached from an
      unsupervised learning procedure. The distribution defining the quantizer is
      represented as a set of separable Laplacian mixture densities for two-dimensional
      images. The condition of identifiability is shown for the Laplacian case and a
      decision directed estimate of both the active distribution parameters and the
      mixing parameters are discussed in view of a Bayesian structure. The decision
      directed estimators, although not optimum, provide a realizable structure for
      estimating the parameters which define a distribution which has become active.
      These parameters are then used to scale the optimum (in the mean square error
      sense) Laplacian quantizer. The decision criteria is modified to prevent
      convergence to a single distribution which in effect is the default condition for
      a variance estimator. This investigation was applied to a test image and the
      resulting data demonstrate improvement over other techniques using fixed bit
      assignments and ideal channel conditions.

PMID- 21869053
TI  - Studies in semi-admissible heuristics.
AB  - The paper introduces three extensions of the A* search algorithm which improve
      the search efficiency by relaxing the admissibility condition. 1) A* employs an
      admissible heuristic function but invokes quicker termination conditions while
      still guaranteeing that the cost of the solution found will not exceed the
      optimal cost by a factor greater than 1 + . 2) R?* may employ heuristic functions
      which occasionally violate the admissibility condition, but guarantees that at
      termination the risk of missing the opportunity for further cost reduction is at
      most ?. 3) R?*,* is a speedup version of R?*, combining the termination condition
      of A* with the risk-admissibility condition of R?*. The Traveling Salesman
      problem was used as a test vehicle to examine the performances of the algorithms
      A* and R?*. The advantages of A* are shown to be significant in difficult
      problems, i.e., problems requiring a large number of expansions due to the
      presence of many subtours of roughly equal costs. The use of R?* is shown to
      produce a 4:1 reduction in search time with only a minor increase in final
      solution cost.

PMID- 21869054
TI  - An experimental study of some algorithms for unsupervised learning.
AB  - Three well-known algorithms for unsupervised learning using a decision-directed
      approach are the random labeling of patterns according to the estimated a
      posteriori probabilities, the classification according to the estimated a
      posteriori probabilities, and the iterative solution of the maximum likelihood
      equations. The convergence properties of these algorithms are studied by using a
      sample of about 10 000 handwritten numerals. It turns out that the iterative
      solution of the maximum likelihood equations has the best properties among the
      three approaches. However, even this one fails to yield satisfactory results if
      the number of unknown parameters becomes large, as is usually the case in
      realistic problems of pattern recognition.

PMID- 21869055
TI  - A graph-theoretic method for decomposing two-dimensional polygonal shapes into
      meaningful parts.
AB  - This note gives a new graph-theoretic shape decomposition procedure, extending
      the idea in the paper ''Decomposition of Two-Dimensional Shapes by Graph
      Theoretic Clustering'' by Shapiro and Haralick [1]. A binary matrix is used in
      order to express the LI relation. A solution for the problems connected with
      artificial separation of two CS cliques and the presence of a regular concavity
      is proposed. Our algorithm produces nonoverlapping shape parts in much reduced
      execution time.

PMID- 21869056
TI  - Segmentation of images having unimodal distributions.
AB  - A gradient relaxation method based on maximizing a criterion function is studied
      and compared to the nonlinear probabilistic relaxation method for the purpose of
      segmentation of images having unimodal distributions. Although both methods
      provide comparable segmentation results, the gradient method has the additional
      advantage of providing control over the relaxation process by choosing three
      parameters which can be tuned to obtain the desired segmentation results at a
      faster rate. Examples are given on two different types of scenes.

PMID- 21869057
TI  - A medial axis transformation for grayscale pictures.
AB  - Blum's medial axis transformation (MAT) for binary pictures yields medial axis
      points that lie midway between opposite borders of a region or along angle
      bisectors. This note discusses a generalization of the MAT in which a score is
      computed for each point P of a grayscale picture based on the gradient magnitudes
      at pairs of points that have P as their midpoint. These scores are high at points
      that lie midway between pairs of antiparallel edges or along angle bisectors, so
      that they define a MAT-like ''skeleton,'' which we may call the GRADMAT. However,
      this skeleton is rather sensitive to the presence of noise edges or to
      irregularities in the region edges, and it also is subject to artifacts created
      by pairs of edges belonging to different objects.

PMID- 21869058
TI  - An on-line procedure for recognition of handprinted alphanumeric characters.
AB  - This correspondence presents a procedure to recognize handprinted alphanumeric
      characters written on a graphic tablet. After preprocessing, the input character
      is segmented into a polygon using a simple segmentation procedure. A feature
      vector is formed by the parameters which describe the segments of the polygon.
      Classification is done in two steps, the first one based on structural
      information extracted from the feature vector and the second based on statistical
      decision rule using parameters of the segments. A recursive learning procedure is
      introduced in the statistical classifier. The evaluation includes the measurement
      of recognition rates using several statistical classifiers, the validity test on
      the hypothesis concerning the distribution of feature vectors and the possibility
      of further simplification using principal axis analysis. Databases were created
      and used for the evaluation.

PMID- 21869059
TI  - A nonparametric two-dimensional display for classification.
AB  - A two-dimensional display whose coordinates are related to the distance to the
      kth-nearest neighbor of each class is presented. Applications of the display to
      minimum error, minimum cost, minimax, and Neyman-Pearson type classifier designs
      are given. The display is shown to present risk information in a manner that
      easily allows the specification of reject regions. Two methods of error
      estimation using the display, an error counting technique and a risk averaging
      method, are detailed. It is shown that the classifiers that result are
      generalizations of the standard k-NN majority vote classifier. As a result of the
      properties of the display, classifiers can be readily evaluated and modified. In
      addition, a condensing algorithm that preserves the nearest neighbor error count
      of any preclassified data set is described. The display is used to graphically
      illustrate the distance relationships that are central to the algorithm.

PMID- 21869060
TI  - Performance evaluations of correlations of digital images using different
      separability measures.
AB  - A comparison of four separability measures which are useful in the registration
      of two-dimensional images is presented. Bayes probability of error, Chernoff
      bound, Bhattacharyya bound, and Fisher's criteria are used in the selection of
      the appropriate reference images from a set of aerial pictures, each exhibiting a
      different view of a scene, i.e., down-looking and target-looking. The experiment
      is repeated for corresponding synthetic images of this scene. Both area and edge
      correlations are used. A comparison of the measures and the resulting
      probabilities of error is made. The results show that for real images the target
      looking view performs better than the down-looking view for both area and edge
      correlations. For synthetic images, the down-looking view performs better than
      the target-looking view for both area and edge correlations. The variation in
      synthetic images between the target-looking and the down-looking views is larger
      than in the real images for both area and edge correlations.

PMID- 21869061
TI  - Hierarchical classifier design using mutual information.
AB  - A nonparametric algorithm is presented for the hierarchical partitioning of the
      feature space. The algorithm is based on the concept of average mutual
      information, and is suitable for multifeature multicategory pattern recognition
      problems. The algorithm generates an efficient partitioning tree for specified
      probability of error by maximizing the amount of average mutual information gain
      at each partitioning step. A confidence bound expression is presented for the
      resulting classifier. Three examples, including one of handprinted numeral
      recognition, are presented to demonstrate the effectiveness of the algorithm.

PMID- 21869062
TI  - Fuzzy tree automata and syntactic pattern recognition.
AB  - An approach of representing patterns by trees and processing these trees by fuzzy
      tree automata is described. Fuzzy tree automata are defined and investigated. The
      results include that the class of fuzzy root-to-frontier recognizable ?-trees is
      closed under intersection, union, and complementation. Thus, the class of fuzzy
      root-to-frontier recognizable ?-trees forms a Boolean algebra. Fuzzy tree
      automata are applied to processing fuzzy tree representation of patterns based on
      syntactic pattern recognition. The grade of acceptance is defined and
      investigated. Quantitative measures of ''approximate isosceles triangle,''
      ''approximate elongated isosceles triangle,'' ''approximate rectangle,'' and
      ''approximate cross'' are defined and used in the illustrative examples of this
      approach. By using these quantitative measures, a house, a house with high roof,
      and a church are also presented as illustrative examples. In addition, three
      fuzzy tree automata are constructed which have the capability of processing the
      fuzzy tree representations of ''fuzzy houses,'' ''houses with high roofs,'' and
      ''fuzzy churches,'' respectively. The results may have useful applications in
      pattern recognition, image processing, artificial intelligence, pattern database
      design and processing, image science, and pictorial information systems.

PMID- 21869063
TI  - Computational cost of image registration with a parallel binary array processor.
AB  - The application of a simulated binary array processor (BAP) to the rapid analysis
      of a sequence of images has been studied. Several algorithms have been developed
      which may be implemented on many existing parallel processing machines. The
      characteristic operations of a BAP are discussed and analyzed. A set of
      preprocessing algorithms are described which are designed to register two images
      of TV-type video data in real time. These algorithms illustrate the potential
      uses of a BAP and their cost is analyzed in detail. The results of applying these
      algorithms to FLIR data and to noisy optical data are given. An analysis of these
      algorithms illustrates the importance of an efficient global feature extraction
      hardware for image understanding applications.

PMID- 21869064
TI  - Mathematical structures of line drawings of polyhedrons-toward man-machine
      communication by means of line drawings.
AB  - Mathematical structures of line drawings of polyhedrons are studied and practical
      as well as theoretical solutions are obtained for several fundamental problems
      aroused in scene analysis and in man-machine communication. First, a necessary
      and sufficient condition for a line drawing to correctly represent a polyhedron
      is obtained in terms of linear algebra. Next, combinatorial structures are
      investigated and practical solutions are obtained to such problems as how to
      discriminate between correct and incorrect line drawings and how to correct
      vertex-position errors in incorrect line drawings. Lastly, distribution of the
      degree of freedom of a line drawing is elucidated and a method is proposed for
      interactive reconstruction of a polyhedron from a line drawing. The results
      obtained here enable us to make manmachine communication more ''flexible'' in the
      sense that a machine can reconstruct three-dimensional objects from hand-drawn
      pictures even if the pictures are not perfect.

PMID- 21869065
TI  - Identification of space curves from two-dimensional perspective views.
AB  - This paper describes a new method to be used for matching three-dimensional
      objects with curved surfaces to two-dimensional perspective views. The method
      requires for each three-dimensional object a stored model consisting of a closed
      space curve representing some characteristic connected curved edges of the
      object. The input is a two-dimensional perspective projection of one of the
      stored models represented by an ordered sequence of points. The input is
      converted to a spline representation which is sampled at equal intervals to
      derive a curvature function. The Fourier transform of the curvature function is
      used to represent the shape. The actual matching is reduced to a minimization
      problem which is handled by the Levenberg-Marquardt algorithm [3].

PMID- 21869066
TI  - Locating structures in aerial images.
AB  - A technique for locating desired structures utilizing user specified information
      about properties of these structures and their relationships with other more
      easily extracted objects is described. An edge-based and region-based technique
      is used for scene segmentation. Experimental results of the processing of aerial
      pictures are presented.

PMID- 21869067
TI  - Automata in random environments with application to machine intelligence.
AB  - Computers and brains are modeled by finite and probabilistic automata,
      respectively. Probabilistic automata are known to be strictly more powerful than
      finite automata. The observation that the environment affects behavior of both
      computer and brain is made. Automata are then modeled in an environment. Theorem
      1 shows that useful environmental models are those which are infinite sets. A
      probabilistic structure is placed on the environment set. Theorem 2 compares the
      behavior of finite (deterministic) and probabilistic automata in random
      environments. Several interpretations of Theorem 2 are discussed which offer some
      insight into some mathematical limits of machine intelligence.

PMID- 21869068
TI  - Some graphical considerations in time series analysis.
AB  - The pictorial information in a stationary time series as depicted by crossings of
      levels and crossings of random levels and related quantities is studied. It is
      shown that such graphical features are directly connected with the covariance
      function and hence with the spectral density. Many of these features can be
      actually applied in estimation and in the study of extremes. In the Gaussian
      case, the finite dimensional distributions are completely determined by the axis
      crossings and by the crossings of a random curve (to be defined) if the process
      is essentially bounded. Certain graphical patterns are suggested for a fast
      recognition of low-order ARMA models.

PMID- 21869069
TI  - Region extraction from complex shapes.
AB  - An algorithm is described which extracts primitive regions (i.e., convex, spiral
      shaped, and biconcave lens) from complex shapes. The interior region bounded by
      the shape is decomposed by first slicing it into a set of convex subregions and
      then rotating and dissolving the various boundaries between subregions until a
      satisfactory decomposition is obtained. The same algorithm also is used to
      decompose the exterior region between the shape and its convex hull. The
      algorithm has been implemented as an Algol-W computer program for the UNIVAC
      90/80 and results of running the program are presented for a wide variety of
      complex shapes. These results compare favorably with the experience reported by
      previous programs.

PMID- 21869070
TI  - Efficient calculation of primary images from a set of images.
AB  - A set of images is modeled as a stochastic process and Karhunen-Loeve expansion
      is applied to extract the feature images. Although the size of the correlation
      matrix for such a stochastic process is very large, we show the way to calculate
      the eigenvectors when the rank of the correlation matrix is not large. We also
      propose an iterative algorithm to calculate the eigenvectors which save
      computation time andc omputer storage requirements. This iterative algorithm
      gains its efficiency from the fact that only a significant set of eigenvectors
      are retained at any stage of iteration. Simulation results are also presented to
      verify these methods.

PMID- 21869071
TI  - Moving target tracking using symbolic registration.
AB  - This correspondence describes a moving target tracking (MTT) algorithm that
      performs image registration and motion analysis between pairs of images from a
      passive sensor. Unlike previously reported moving target indicators that operate
      at the signal level, the registration and motion analysis in the MTT is totally
      performed at a symbolic level. The operation of the MTT is demonstrated by
      simulation results obtained from applications of the algorithm to infrared
      images.

PMID- 21869072
TI  - Experiments in Text Recognition with Binary n-Gram and Viterbi Algorithms.
AB  - The binary n-gram and Viterbi algorithms have been suggested as alternative
      approaches to contextual postprocessing for text produced by a noisy channel such
      as an optical character recognizer. This correspondence describes the underlying
      theory of each approach in unified terminology, and presents new implementation
      algorithms for each approach. In particular, a storage efficient data structure
      is proposed for the binary n-gram algorithm and a recursive formulation is given
      for the Viterbi algorithm. Results of extensive experiments with each algorithm
      are described.

PMID- 21869073
TI  - The use of shrinkage estimators in linear discriminant analysis.
AB  - Probably the most common single discriminant algorithm in use today is the linear
      algorithm. Unfortunately, this algorithm has been shown to frequently behave
      poorly in high dimensions relative to other algorithms, even on suitable Gaussian
      data. This is because the algorithm uses sample estimates of the means and
      covariance matrix which are of poor quality in high dimensions. It seems
      reasonable that if these unbiased estimates were replaced by estimates which are
      more stable in high dimensions, then the resultant modified linear algorithm
      should be an improvement. This paper studies using a shrinkage estimate for the
      covariance matrix in the linear algorithm. We chose the linear algorithm, not
      because we particularly advocate its use, but because its simple structure allows
      one to more easily ascertain the effects of the use of shrinkage estimates. A
      simulation study assuming two underlying Gaussian populations with common
      covariance matrix found the shrinkage algorithm to significantly outperform the
      standard linear algorithm in most cases. Several different means, covariance
      matrices, and shrinkage rules were studied. A nonparametric algorithm, which
      previously had been shown to usually outperform the linear algorithm in high
      dimensions, was included in the simulation study for comparison.

PMID- 21869074
TI  - A dimensionality reduction technique based on a least squared error criterion.
AB  - A method of achieving dimensionality reduction is presented. The reduced
      dimensionality is achieved by utilizing a least squared error technique under the
      assumption that the goodness criterion is the maximum separation of classes. The
      criterion is met by first maximizing the spread of the cluster centers, and then
      minimizing the within class scatter. The derivation of the desired transformation
      from an arbitrary p-space to a space of lower dimension, say l, is completed with
      the assumption that the cluster centers are known. The criterion for the cluster
      center location is the minimization of the variance of the distance between the
      cluster center and the transformed pattern. It is demonstrated that the resulting
      cluster center set is similar to the simplex signal set in communication theory,
      which is a minimum energy signal set.

PMID- 21869075
TI  - Discrete optimization by relational constraint satisfaction.
AB  - In pattern matching a basic problem is to determine one or more vectors X that
      maximize an objective function which is a sum of functions of components of X.
      When this problem is solved by dynamic programming CPU time and storage
      requirements grow explosively as the amount of intervariable interaction in the
      objective function increases. This explosion may be reduced by departing from the
      traditional dynamic programming method of eliminating successive variables and
      instead determining a constraint relation between each variable and all others
      with which it interacts. Discrete relaxation is used to accelerate a backtrack
      search to find all vectors that satisfy all such constraints. Optimization is
      achieved by evaluating the objective function for all such vectors. This new
      method of optimization has been experimentally compared with a classical dynamic
      programming algorithm running with the same pseudorandomly generated objective
      functions.

PMID- 21869076
TI  - New algorithm for the slant transform.
AB  - Two new algorithms that are more convenient for computation than existing ones
      for the slant transform are developed. These algorithms reveal the close
      relationship between the slant transform and the Walsh-Hadamard transform and
      demonstrate that the slant transform may be approached by a series of steps which
      gradually change the transform from a Hadamard or Walsh transform to a slant
      transform.

PMID- 21869077
TI  - A system for programming and controlling sensor-based robot manipulators.
AB  - This paper describes an approach to programming and controlling robot
      manipulators which facilitates the use of sensory information. Robot actions are
      specified by declaring software servo processes which control the robot's various
      degrees of freedom. These servo processes can involve position, orientation,
      force, and torque information from the robot itself, or data from external
      sensors. Robot tasks are programmed by dynamically modifying the servo processes
      or by changing set points to these processes. Condition monitors, which have
      access to program and sensory information, detect the completion of program
      steps.

PMID- 21869078
TI  - Boundary location from an initial plan: the bead chain algorithm.
AB  - A new boundary finding method is described and applied to a problem in
      morphometric cytology. The method is shown to offer several advantages over
      existing boundary locating techniques. Some experimental results are presented.

PMID- 21869079
TI  - Restoration of a feature closed class of two-dimensional images.
AB  - A restoration principle is proposed and demonstrated for a feature closed class
      of two-dimensional images. Any member of this class of images can be represented
      as an intersection of unions of half planes in R2. Images with corners as well as
      images with continuous curvature can be generated under this algebraic
      representation. All resulting images have a well-defined interior and a
      nonintersecting boundary. Knowledge that the image to be restored comes from this
      closed class of images allows for an image restoration algorithm that is superior
      to a point-thickening algorithm. The proposed restoration algorithm produces a
      restored image that lies within the image to be restored. For a random sample of
      n points known to lie within the image to be restored, the expected value of the
      residual area for the image with corners is of order (In n/n) and is proportional
      to the number of outside corners. For images with continuous curvature, the
      residual area is of order 1/?n and is proportional to a geometric constant
      associated with the curvature of the boundary. The restoration algorithm offers
      insight into the consideration of the shape of the boundary in image restoration.

PMID- 21869080
TI  - Markov random field texture models.
AB  - We consider a texture to be a stochastic, possibly periodic, two-dimensional
      image field. A texture model is a mathematical procedure capable of producing and
      describing a textured image. We explore the use of Markov random fields as
      texture models. The binomial model, where each point in the texture has a
      binomial distribution with parameter controlled by its neighbors and ''number of
      tries'' equal to the number of gray levels, was taken to be the basic model for
      the analysis. A method of generating samples from the binomial model is given,
      followed by a theoretical and practical analysis of the method's convergence.
      Examples show how the parameters of the Markov random field control the strength
      and direction of the clustering in the image. The power of the binomial model to
      produce blurry, sharp, line-like, and blob-like textures is demonstrated. Natural
      texture samples were digitized and their parameters were estimated under the
      Markov random field model. A hypothesis test was used for an objective assessment
      of goodness-of-fit under the Markov random field model. Overall, microtextures
      fit the model well. The estimated parameters of the natural textures were used as
      input to the generation procedure. The synthetic microtextures closely resembled
      their real counterparts, while the regular and inhomogeneous textures did not.

PMID- 21869081
TI  - The effect of cluster size, dimensionality, and the number of clusters on
      recovery of true cluster structure.
AB  - An evaluation of four clustering methods and four external criterion measures was
      conducted with respect to the effect of the number of clusters, dimensionality,
      and relative cluster sizes on the recovery of true cluster structure. The four
      methods were the single link, complete link, group average (UPGMA), and Ward's
      minimum variance algorithms. The results indicated that the four criterion
      measures were generally consistent with each other, of which two highly similar
      pairs were identified. The tirst pair consisted of the Rand and corrected Rand
      statistics, and the second pair was the Jaccard and the Fowlkes and Mallows
      indexes. With respect to the methods, recovery was found to improve as the number
      of clusters increased and as the number of dimensions increased. The relative
      cluster size factor produced differential performance effects, with Ward's
      procedure providing the best recovery when the clusters were of equal size. The
      group average method gave equivalent or better recovery when the clusters were of
      unequal size.

PMID- 21869082
TI  - Classification by thresholding.
AB  - A procedure is given which substantially reduces the processing time needed to
      perform maximum likelihood classification on large data sets. The given method
      uses a set of fixed thresholds which, if exceeded by one probability density
      function, makes it unnecessary to evaluate a competing density function. Proofs
      are given of the existence and optimality of these thresholds for the class of
      continuous, unimodal, and quasi-concave density functions (which includes the
      multivariate normal), and a method for computing the thresholds is provided for
      the specifilc case of multivariate normal densities. An example with remote
      sensing data consisting of some 20 000 observations of four-dimensional data from
      nine ground-cover classes shows that by using thresholds, one could cut the
      processing time almost in half.

PMID- 21869083
TI  - Gray level image processing by cellular logic transforms.
AB  - The cellular logic transform has been used extensively in the analysis of bilevel
      images generated by thresholding gray level images. Now, by a process of gray
      level resynthesis, it is shown to be useful in gray level image processing.

PMID- 21869084
TI  - Direct computation of the focus of expansion.
AB  - Optical flow carries valuable information about the nature and depth of surfaces
      and the relative motion between observer and objects. In the extraction of this
      information, the focus of expansion plays a vital role. In contrast to the
      current approaches, this paper presents a method for the direct computation of
      the focus of expansion using an optimization approach. The optical flow can then
      be computed using the focus of expansion.

PMID- 21869085
TI  - Segmentation by texture using correlation.
AB  - The correlation coefficients are used for segmentation according to texture. They
      are first evaluated on a set of square regions forming two levels of the
      quadratic picture tree (or pyramid). If the coefficients of a square and its four
      children in the tree are similar, then that region is considered to be of uniform
      texture. If not, it is replaced by its children. In this way, the split-and-merge
      algorithm is used to achieve a preliminary segmentation. It is followed by a
      grouping algorithm using the correlation coefficients and the region adjacency
      graph, plus a small region elimination step. The latter regions are grouped
      according to their gray level because texture cannot be defined reliably on very
      small regions. Examples of implementation on four pictures are included.

PMID- 21869086
TI  - On edge detection of x-ray images using fuzzy sets.
AB  - The effectiveness of the theory of fuzzy sets in detecting different regional
      boundaries of X-ray images is demonstrated. The algorithm includes a prior
      enhancement of the contrast among the regions (having small change in gray
      levels) using the contrast intensification (INT) operation along with smoothing
      in the fuzzy property plane before detecting its edges. The property plane is
      extracted from the spatial domain using S, ? and (1 ?) functions and the
      fuzzifiers. Final edge detection is achieved using max or min operator. The
      system performance for different parameter conditions is illustrated by
      application to an image of a radiograph of the wrist.

PMID- 21869087
TI  - Optimal quadtrees for image segments.
AB  - Quadtrees are compact hierarchical representations of images. In this paper, we
      define the efficiency of quadtrees in representing image segments and derive the
      relationship between the size of the enclosing rectangle of an image segment and
      its optimal quadtree. We show that if an image segment has an enclosing rectangle
      having sides of lengths x and y, such that 2N-1 * max (x, y) ? 2N, then the
      optimal quadtree may be the one representing an image of size 2N * 2N or 2N+1 *
      2N+1. It is shown that in some situations the quadtree corresponding to the
      larger image has fewer nodes. Also, some necessary conditions are derived to
      identify segments for which the larger image size results in a quadtree which is
      no more expensive than the quadtree for the smaller image size.

PMID- 21869088
TI  - Application of a multilayer decision tree in computer recognition of chinese
      characters.
AB  - A multistage classifier with general tree structure has been developed to
      recognize a large number of Chinese characters. A simple and efficient method of
      classifying the characters was achieved by choosing the best feature at each
      stage of the tree. The features used are Walsh coefficients obtained from two
      profiles of a character projected onto the X-Y orthogonal axes. Some algorithms
      for aligning the characters were compared and one of them was adopted in this
      recognition scheme. A high recognition rate of about 99.5 percent was obtained in
      an experiment with more than 3000 different Chinese characters.

PMID- 21869089
TI  - Improved speedup bounds for parallel alpha-Beta search.
AB  - In this paper we investigate the ''mandatory-work-first'' approach to parallel
      alpha-beta search first proposed by Akl, Barnard, and Doran. This approach is
      based on a version of alpha-beta search without deep cutoffs and a two-stage
      evaluation process, the second stage of which is often pruned. Our analysis shows
      that for best-first ordering on the lookahead tree, this approach provides
      greater speedup than the Palphabeta tree-splitting technique, and that for worst
      first ordering, mandatory work first provides only slightly worse speedup than
      Palphabeta.

PMID- 21869090
TI  - Hierarchical structures and complexities of parallel isometric languages.
AB  - The relationship between parallel isometric array languages and sequential
      isometric array languages is examined. Their hierarchical structures are
      investigated and a hierarchy is established by introducing parallel context-free
      array languages (PCFAL), derivation bounded array languages (DBAL), linear array
      languages (LAL), and extended regular afray languages (ERAL). It is interesting
      to find that some fundamental aspects that hold in one-dimensional string
      languages do not hold in their two-dimensional counterparts. Some parsing
      techniques are also explored. It is shown that while parallel parsing grammars
      may be simpler to write and parallel processing usually takes less time than
      sequential ones, the nature of parallel parsing is very complicated. Finally,
      several future research topics concerned with parallel isometric array languages
      including their complexities, hierarchical structures, and application to pattern
      recognition are discussed.

PMID- 21869091
TI  - Fisher discriminant analysis and factor analysis.
AB  - We show that information on the inherent structure of multidimensional data
      derived from a factor analysis procedure is equivalent to information obtained by
      Fisher discriminant analysis techniques, provided certain conditions, usually
      required in the factor analysis model, are satisfied. The results advocate the
      use of a factor analysis approach when Fisher discriminant analysis is not
      applicable, such as, for instance, in clustering problems.

PMID- 21869092
TI  - Segmenting dot patterns by voronoi diagram concavity.
AB  - This correspondence defines a signed distance, called ''internal concavity,'' on
      paths of the Voronoi diagram of a dot pattern. An algorithm using internal
      concavity to segment dot patterns is described. The segmentation algorithm
      produces subsets of the Dirichlet tessellation (Delaunay triangulation) of the
      dot pattern.

PMID- 21869093
TI  - Packing volumes by spheres.
AB  - In this note we present an algorithm for packing spheres in an arbitrary shaped
      volume. This algorithm is similar to Blum's transform in that it fits spheres
      into a volume, but it is different in that it fits only tangential spheres, and
      thereby the data reduction is larger than by Blum's transform. The spheres are of
      variable radii, which enables us to achieve a hierarchy of intrinsic volume
      properties, i.e., from gross to more detailed. The result of this algorithm is a
      graph where the nodes are the centers of spheres and the arcs are the connections
      between two tangent spheres. Analysis of computational complexity and the time
      and error considerations are provided.

PMID- 21869094
TI  - A perspective on range finding techniques for computer vision.
AB  - In recent times a great deal of interest has been shown, amongst the computer
      vision and robotics research community, in the acquisition of range data for
      supporting scene analysis leading to remote (noncontact) determination of
      configurations and space filling extents of three-dimensional object assemblages.
      This paper surveys a variety of approaches to generalized range finding and
      presents a perspective on their applicability and shortcomings in the context of
      computer vision studies.

PMID- 21869095
TI  - Model-based three-dimensional interpretations of two-dimensional images.
AB  - ACRONYM is a comprehensive domain independent model-based system for vision and
      manipulation related tasks. Many of its submodules and representations have been
      described elsewhere. Here the derivation and use of invariants for image feature
      prediction is described. Predictions of image features and their relations are
      made from three-dimensional geometric models. Instructions are generated which
      teli the interpretation algorithms how to make use of image feature measurements
      to derive three-dimensional size, structural, and spatial constraints on the
      original three-dimensional models. Some preliminary examples of ACRONYM's
      interpretations of aerial images are shown.

PMID- 21869096
TI  - Volumetric descriptions of objects from multiple views.
AB  - Occluding contours from an image sequence with view-point specifications
      determine a bounding volume approximating the object generating the contours. The
      initial creation and continual refinement of the approximation requires a
      volumetric representation that facilitates modification yet is descriptive of
      surface detail. The ''volume segment'' representation presented in this paper is
      one such representation.

PMID- 21869097
TI  - Multiframe image point matching and 3-d surface reconstruction.
AB  - This paper presents two new methods, the Joint Moment Method (JMM) and the Window
      Variance Method (WVM), for image matching and 3-D object surface reconstruction
      using multiple perspective views. The viewing positions and orientations for
      these perspective views are known a priori, as is usually the case for such
      applications as robotics and industrial vision as well as close range
      photogrammetry. Like the conventional two-frame correlation method, the JMM and
      WVM require finding the extrema of 1-D curves, which are proved to theoretically
      approach a delta function exponentially as the number of frames increases for the
      JMM and are much sharper than the two-frame correlation function for both the JMM
      and the WVM, even when the image point to be matched cannot be easily
      distinguished from some of the other points. The theoretical findings have been
      supported by simulations. It is also proved that JMM and WVM are not sensitive to
      certain radiometric effects. If the same window size is used, the computational
      complexity for the proposed methods is about n - 1 times that for the two-frame
      method where n is the number of frames. Simulation results show that the JMM and
      WVM require smaller windows than the two-frame correlation method with better
      accuracy, and therefore may even be more computationally feasible than the latter
      since the computational complexity increases quadratically as a function of the
      window size.

PMID- 21869098
TI  - Detection of edges using range information.
AB  - Range data provide an important source of 3-D shape information. This information
      can be used to extract jump boundaries which correspond to occluding boundaries
      of objects in a scene and ''edges'' which correspond to points lying between
      significantly different regions on the surface of objects. We are mainly
      interested in range data obtained from sensors such as lasers. The main problem
      with this type of range finder is the fact that the accuracy of the measurements
      depends on the power of the signal that reaches the receiver. This study
      describes how a range edge detection procedure can be designed that has low
      sensitivity to noise and imbeds all the knowledge available on the range
      measurement accuracy.

PMID- 21869099
TI  - A maximum likelihood approach to continuous speech recognition.
AB  - Speech recognition is formulated as a problem of maximum likelihood decoding.
      This formulation requires statistical models of the speech production process. In
      this paper, we describe a number of statistical models for use in speech
      recognition. We give special attention to determining the parameters for such
      models from sparse data. We also describe two decoding methods, one appropriate
      for constrained artificial languages and one appropriate for more realistic
      decoding tasks. To illustrate the usefulness of the methods described, we review
      a number of decoding results that have been obtained with them.

PMID- 21869100
TI  - A new implementation of the mellin transform and its application to radar
      classification of ships.
AB  - A modified Mellin transform for digital implementation is developed and applied
      to range radar profiles of naval vessels. The scale invariance property of the
      Mellin transform provides a means for extracting features from the profiles which
      are insensitive to the aspect angle of the radar. Past implementations of the
      Mellin transform based on the FFT have required exponential sampling,
      interpolation, and the computation of a correction term, all of which introduce
      errors into the transform. In addition, exponential sampling results in a factor
      of ln N increase in the number of data points. An alternate implementation,
      developed in the paper, utilizes a direct expansion of the Mellin integral
      definition. This direct Mellin transform (DMT) eliminates the implementation
      problems associated with the FFT approach, and does not increase the number of
      samples. A scale and translation invariant transform is developed from a
      modification of the DMT. The MDMT applied to the FFT of the radar profiles
      results in the desired insensitivity without having the low-pass filtering
      characteristic that exists in other Fourier-Mellin implementations.

PMID- 21869101
TI  - Candide's Practical Principles of Experimental Pattern Recognition.
AB  - This correspondence calls attention to several frequently used assumptions and
      techniques culled from the pattern recognition literature.

PMID- 21869102
TI  - Bounds on (deterministic) correlation functions with application to registration.
AB  - The auto/cross correlation of L2 functions are constrained by certain bounds
      which may often be used to advantage. These bounds apply to all the common cross
      correlation functions used for registration purposes (called ''deterministic''
      correlation functions in this paper, as opposed to stochastic correlation based
      on non-L2 functions). It is shown that the envelopes of deterministic
      autocorrelations have essentially a cosine-like behavior but with jump
      discontinuities at points where the normalized relative displacement is the
      reciprocal of an integer. Several inequalities extending these results are given.
      It is shown how these can be applied toward obtaining improved registration
      algorithms.

PMID- 21869103
TI  - Solving problems in robotics with semantic networks.
AB  - Robot problems are examined in the context of semantic networks which are used to
      represent the state of a problem and the operators useful for solving it. Graph
      transformation algorithms are discussed as an aid to problem solving. Although
      these form only a small subset of the first-order predicate calculus based
      systems, considerations such as subgoal circularity, partially specified states
      and multiple manipulators sharing the same environment may warrant this
      simplification.

PMID- 21869104
TI  - An intelligent tactile sensor-an on-line hierarchical object and seam analyzer.
AB  - This paper describes an on-line computer supported tactile sensor that can
      recognize complex industrial objects, identify a seam location, and track a three
      dimensional seam trajectory for an arc welding robot. A one finger tactile sensor
      with two degrees of freedom is used. The supporting microcomputer system
      organizes and reduces the useful sensor data from digitized tactile information
      to a compact symbolic representation which is matched to a knowledge network. A
      beam search algorithm is used. The hierarchical organization provides that simple
      features are first detected on the object, and more complex features are examined
      later. Pruning of the search tree is based on a likelihood function.

PMID- 21869105
TI  - On the stability of shared near neighbor clustering.
AB  - This correspondence concentrates on the detection of stable clustering results
      when using the nonparmetric clustering technique of Jarvis and Patrick. This
      technique incorporates the concept of similarity based on sharing of near
      neighbors. Essentially, in this clustering scheme, two parameters are involved:
      neighborhood depth and similarity threshold. Combining a penalty for chaining
      with the detection of so-called hierarchical stable solutions in the field of all
      possible solutions, due to the setting of the two parameters, is experimentally
      shown to provide a powerful method for discriminating between reliable and
      unreliable results.

PMID- 21869106
TI  - Evaluating Multimembership Classifiers: A Methodology and Application to the
      MEDAS Diagnostic System.
AB  - Performance evaluation measures for multimembership classifiers are presented and
      applied in a retrospective study on the diagnostic performance of the MEDAS
      (Medical Emergency Decision Assistance System) system. Admission and discharge
      diagnoses for 122 patients with one or more of 26 distinct disorders in five
      major disorder categories were gathered. The average number of disorders per
      patient was 2 with 36 (29.5 percent) patients having 3 or more disorders
      simultaneously. The features (symptoms, signs, and laboratory data) available at
      admission were entered into a multimembership Bayesian pattern recognition
      algorithm which permits for diagnosis of multiple disorders. When the top five
      computer-ranked diagnoses were considered, all of the correct diagnoses for 86.1
      percent of the patients were displayed by the fifth position. In 71.6 percent of
      these cases, no false diagnosis preceded any correct diagnosis. In ten cases a
      discharge diagnosis which was suggested by the available findings was omitted by
      the admitting physician. In six of these ten cases, the overlooked diagnoses
      appeared at the computer ranked list above all false diagnoses. Considering the
      urgency of diagnosis in the Emergency Department, the high uncertainty involved
      due to the limited availability of data, and the high frequency with which
      multiple disorders coexist, this limited study encourages our confidence in the
      MEDAS knowledge base and algorithm as a useful diagnostic support tool.

PMID- 21869107
TI  - Application of k-Nearest-Neighbor Decision Rule in Vowel Recognition.
AB  - The k-nearest-neighbor decision rule is known to provide a useful nonparametric
      procedure for pattern classification. This rule is applied here to a vowel
      recognition problem and the effect of the number (k) of nearest neighbors, the
      size of the trained set and the type of the distance measure on vowel recognition
      performance is studied. It is shown that the vowel recognition performance
      remains approximately constant for all the values of k. The recognition
      performance initially improves with the size of the training set and then
      converges to an asymptotic value. Selection of a better distance measure leads to
      a significant improvement in vowel recognition performance.

PMID- 21869108
TI  - Three-dimensional digital line segments.
AB  - Digital arcs in 3-D digital pictures are defined. The digital image of an arc is
      also defined. A digital arc is defined to be a digital line segment if it is the
      digital image of a line segment. It is shown that a digital line segment may be
      characterized by the chord property holding for its projections onto the
      coordinate planes. It is also shown that a digital line segment may not be
      characterized by its own chord property. A linear time algorithm is presented
      that determines whether or not a digital arc is a digital line segment.

PMID- 21869109
TI  - Contexts and data dependencies: a synthesis.
AB  - Two data-organization devices that have come out of AI re-search are data pools
      (''contexts'') and data dependencies. The latter are more flexible than the
      former, and have supplanted them. Data pools offer certain advantages of
      efficiency, however, so it is worth trying to make the two mechanisms compatible.
      Doing this requires generalizing the mark-and-sweep algorithms that maintain
      consistency in a data-dependency network, so that the labels passed around do not
      simply say whether a datum is IN or OUT, but say which data pools it is present
      in. The revised algorithm is essentially an algorithm for solving simultaneous
      Boolean equations. Other mechanisms are needed for per-forming useful chores like
      maintaining well-founded support links and orchestrating demon calls.

PMID- 21869110
TI  - Planning in time: windows and durations for activities and goals.
AB  - A general purpose automated planner/scheduler is described which generates
      parallel plans to achieve goals with imposed time con-straints. Both durations
      and start time windows may be specified for sets of goal conditions. The parallel
      plans consist of not just actions but also of events (triggered by
      circumstances), inferences, and scheduled events (completely beyond the actor's
      control). Deterministic dura-tions of all such activities are explicitly modeled,
      and may be any com-putable function of the activity variables. A start time
      window for each activity in the plan is updated dynamically during plan
      generation, in order to maintain consistency with the windows and durations of
      adja-cent activities and goals. The plans are tailored around scheduled events.
      The final plan network resembles a PERT chart. From this a schedule of nominal
      start times for each activity is generated. Ex-amples are drawn from the
      traditional blocksworld and also from a real-istic ''Spaceworld,'' in which an
      autonomous spacecraft photographs objects in deep space and transmits the
      information to Earth. The author is with the Information Systems Research
      Section, Jet Propulsion Laboratory, Pasadena, CA 91109.

PMID- 21869111
TI  - On the foundations of relaxation labeling processes.
AB  - A large class of problems can be formulated in terms of the assignment of labels
      to objects. Frequently, processes are needed which reduce ambiguity and noise,
      and select the best label among several possible choices. Relaxation labeling
      processes are just such a class of algorithms. They are based on the parallel use
      of local constraints between labels. This paper develops a theory to characterize
      the goal of relaxation labeling. The theory is founded on a definition of con
      sistency in labelings, extending the notion of constraint satisfaction. In
      certain restricted circumstances, an explicit functional exists that can be
      maximized to guide the search for consistent labelings. This functional is used
      to derive a new relaxation labeling operator. When the restrictions are not
      satisfied, the theory relies on variational cal-culus. It is shown that the
      problem of finding consistent labelings is equivalent to solving a variational
      inequality. A procedure nearly identical to the relaxation operator derived under
      restricted circum-stances serves in the more general setting. Further, a local
      convergence result is established for this operator. The standard relaxation
      labeling formulas are shown to approximate our new operator, which leads us to
      conjecture that successful applications of the standard methods are explainable
      by the theory developed here. Observations about con-vergence and generalizations
      to higher order compatibility relations are described.

PMID- 21869112
TI  - Problem reduction representation for the linguistic analysis of waveforms.
AB  - This paper shows how the nondirectional structural analysis of pattern data can
      be performed by matching a problem reduction representation (PRR) of pattern
      structure with sample data, using a best-first state space search algorithm
      called SSS*. The end result of the matching algorithm is a tree whose nodes
      represent recognized structures in the data. Tip nodes of the tree structure
      correspond to primitives which are recognized in the raw data by curve fitting
      routines. The operators of the algorithm allow the tree to be constructed with a
      combination of top-down or bottom-up steps. The matching of the structure tree to
      waveform segments need not be done in a left-right sequence. Moreover ambiguous
      matches are pursued in a best first order by using state space search with
      partial parse trees as states. A software system called WAPSYS (for waveform
      parsing system) is described, which implements this structural analysis paradigm.
      Experience using WAPSYS to analyze carotid pulse waves is also discussed.

PMID- 21869113
TI  - Multiple-window parallel adaptive boundary finding in computer vision.
AB  - The problem considered in this paper is the estimation of highly variable object
      boundaries in noisy images. Boundaries may be those of a tank in an IR image, a
      spinal canal in a CAT scan, a cloud in a visible light image, etc. Or they may be
      internal to an object such as the boundary between a spherical surface and a
      cylindrical surface in a manufactured object. The focus of the paper is on
      parallel multiple-window boundary estimation algorithms. Here the image field is
      parti-tioned into an array of rectangular windows, and boundary finders are run
      simultaneously within the windows. The boundary segments found within the windows
      are then seamed together to obtain meaningful global boundaries. The entire
      procedure is treated within a maximum likelihood estimation framework that we
      have developed for boundary finding. Although our multiple-window estimation
      approach can be used with a number of local boundary finding algorithms, we
      concen-trate on one which is based on dynamic programming and will produce the
      true maximum likelihood boundary. Some theoretical considera-tions for boundary
      model design and boundary-finding runtime are covered. Included is the use of a
      low computational cost F-test for test-ing whether a window contains a boundary,
      and an analytical treatment which shows that use of coarse pixels with a chi
      square test or an F-test improves the probability of correctly recognizing
      whether a boundary is present in a window.

PMID- 21869114
TI  - Applications of vector fields to image processing.
AB  - We use rotational and curvature properties of vector fields to identify critical
      features of an image. Using vector analysis and dif-ferential geometry, we
      establish the properties needed, and then use these properties in three ways.
      First, our results make it theoretically possible to identify extremal edges of
      an intensity function f(x, y) of two variables by considering the gradient vector
      field V = ?f. There is also enough information in ?f to find regions of high
      curvature (i.e., high curvature of the level paths of f). For color images, we
      use the vector field V = (I, Q). In application, the image is partitioned into a
      grid of squares. On the boundary of each square, V/|V| is sampled, and these unit
      vectors are used as the tangents of a curve ?. The rotation number (or
      topological degree) ?(?) and the average curvature f|??| are computed for each
      square. Analysis of these numbers yields infor-mation on edges and curvature.
      Experimental results from both simu-lated and real data are described.

PMID- 21869115
TI  - A gradient projection algorithm for relaxation methods.
AB  - We consider a particular problem which arises when apply-ing the method of
      gradient projection for solving constrained optimiza-tion and finite dimensional
      variational inequalities on the convex set formed by the convex hull of the
      standard basis unit vectors. The method is especially important for relaxation
      labeling techniques applied to problems in artificial intelligence. Zoutendijk's
      method for finding feasible directions, which is relatively complicated in
      general situations, yields a very simple finite algorithm for this problem. We
      present an extremely simple algorithm for performing the gradient projection and
      an independent verification of its correctness.

PMID- 21869116
TI  - An image transform coding scheme based on spatial domain considerations.
AB  - Image transform coding is first briefly reviewed using conventional viewpoints.
      Then a new spatial domain interpretation is given to image transform coding. An
      improvement based on this viewpoint for the Fourier transform coding, which
      possesses simple spatial domain relations, is presented.

PMID- 21869117
TI  - Optimum recursive filtering of noisy two-dimensional data with sequential
      parameter identification.
AB  - A two-dimensional recursive estimation algorithm based on the asymmetric half
      plane model is described for the problem of MMSE (minimum mean-square error)
      filtering. The optimum filtering problem is solved by formulating the asymmetric
      half-plane ARMA (autoregressive moving average) model for two-dimensional data.
      The sequential parameter identification from the noisy two-dimensional data is
      also discussed, utilizing the stochastic approximation. Experiments were
      performed for real image data, combining the proposed parameter identification
      and estimation algorithms. The results show that this method gives considerable
      improvement in SNR.

PMID- 21869118
TI  - Using pyramids to define local thresholds for blob detection.
AB  - A method of detecting blobs in images is described. The method involves building
      a succession of lower resolution images and looking for spots in these images. A
      spot in a low resolution image corresponds to a distinguished compact region in a
      known position in the original image. Further, it is possible to calculate
      thresholds in the low resolution image, using very simple methods, and to apply
      those thresholds to the region of the original image corresponding to the spot.
      Examples are shown in which variations of the technique are applied to several
      images.

PMID- 21869119
TI  - An iterative approach to region growing using associative memories.
AB  - The postulate is made that ''any computation which can be performed recursively
      can be performed easily and efficiently by iteration coupled with association.''
      The ''easily and efficiently'' part of that postulate is nontrivial to prove, and
      is shown by examples in this paper. The use of association leads directly to
      potential implementation by content-addressable memories. The example addressed
      is region growing, often given as a classical example of the use of recursive
      control structures in image processing. Recursive control structures, however,
      are somewhat awkward to build in hardware, where the intent is to segment an
      image at raster scan rates. This paper describes an algorithm and hardware
      structure capable of per-forming region labeling iteratively at scan rates. Every
      pixel is individually labeled with an identifier signifying to which region it
      belongs. The difficulties which often justify recursion (''U''- and ''N''-shaped
      regions, etc.) are handled by maintaining an equivalence table in hardware,
      transparent to the computer, which reads the labeled pixels. The mechanism for
      updating the region map is explained in detail. Furthermore, simulation of the
      associative memory has been demon-strated to be an effective implementation of
      region growing in a serial computer.

PMID- 21869120
TI  - Object recognition using three-dimensional information.
AB  - This paper describes an approach to the recognition of stacked objects with
      planar and curved surfaces. The system works in two phases. In the learning
      phase, a scene containing a single object is shown one at a time. The range data
      of a scene are obtained by a range finder. The description of each scene is built
      in terms of properties of regions and relations between them. This description is
      stored as an object model. In the recognition phase, an unknown scene is
      described in the same way as in the learning phase. Then the description is
      matched to the object models so that the stacked objects are recognized
      sequentially. Efficient matching is achieved by a combination of data-driven and
      model-driven search processes. Experimental results for blocks and machine parts
      are shown.

PMID- 21869121
TI  - Pseudodistance measures for recognition of curved objects.
AB  - A method for the description and identification of curved objects is described in
      this paper. The shape of a curved object is considered as a surface which is an
      accumulation of horizontal section boundaries. This is described by the
      coefficients of a Fourier series expansion of the proposed representative
      function. Each complicated feature of the shape of the object is decomposed into
      five simple features: elongatedness, horizontal strain, section shape, torsion,
      and displacement. Differences of objects as patterns are defined as
      pseudodistances of corresponding features. Some essential properties such as
      completeness of the pseudodistance family are explained theoretically. Finally,
      experimental results of identification of wooden block models and a doll are
      displayed.

PMID- 21869122
TI  - Depth-first picture expression viewed from digital picture processing.
AB  - A picture coding strategy titled DF-expression (Depth-First picture expression)
      is now studied from another point of view. The basic idea of DF-expression is
      briefly reviewed at first. Its capability in data compression is demonstrated
      using 1024 * 1024 binary pictures. Then the new aspects of DF-expression are
      studied in reference to picture processing algorithm on the coded form. They
      include circular shiftings, spectrum of primitives, logical operations, etc.
      Application of DF-expression to gray images (or multivalued pictures) is the next
      topics of the paper. DF-expression is applicable to bit-plane coding of any
      binary image data. Our conclusion with this point is that the gray code is the
      best binary code system for DF-expression in information preserving sense.
      Information-lossy type data reduction is another topics in this paper. The
      authors propose a new data reduction technique in terms of uniformalization of
      excessively complicated regions in bit-planes. Experimental study follows using a
      256 * 256 sized fourbit test picture. Finally, conclusions and other possibility
      of the applications are remarked.

PMID- 21869123
TI  - An integrated algorithm for text recognition: comparison with a cascaded
      algorithm.
AB  - The use of diverse knowledge sources in text recognition and in correction of
      letter substitution errors in words of text is considered. Three knowledge
      sources are defined: channel characteristics as probabilities that observed
      letters are corruptions of other letters, bottom-up context as letter conditional
      probabilities (when the previous letters of the word are known), and top-down
      context as a lexicon. Two algorithms, one based on integrating the knowledge
      sources in a single step and the other based on sequentially cascading bottom-up
      and top-down processes, are compared in terms of computational/storage
      requirements and results of experimentation.

PMID- 21869124
TI  - Automated construction of classifications: conceptual clustering versus numerical
      taxonomy.
AB  - A method for automated construction of classifications called conceptual
      clustering is described and compared to methods used in numerical taxonomy. This
      method arranges objects into classes representing certain descriptive concepts,
      rather than into classes defined solely by a similarity metric in some a priori
      defined attribute space. A specific form of the method is conjunctive conceptual
      clustering, in which descriptive concepts are conjunctive statements involving
      relations on selected object attributes and optimized according to an assumed
      global criterion of clustering quality. The method, implemented in program
      CLUSTER/2, is tested together with 18 numerical taxonomy methods on two exemplary
      problems: 1) a construction of a classification of popular microcomputers and 2)
      the reconstruction of a classification of selected plant disease categories. In
      both experiments, the majority of numerical taxonomy methods (14 out of 18)
      produced results which were difficult to interpret and seemed to be arbitrary. In
      contrast to this, the conceptual clustering method produced results that had a
      simple interpretation and corresponded well to solutions preferred by people.

PMID- 21869125
TI  - Estimation of the parameters of a gaussian mixture using the method of moments.
AB  - Given a general n-dimensional bimodal Gaussian mixture, this paper shows how
      unknown parameters may be found by the method of moments. Three cases are
      considered-equal modal probabilities, known but not necessarily equal
      probabilities, and all parameters unknown. The solution involves sample moments
      no higher than fourth order. For Gaussian mixtures where the number of modes is
      unknown, fourth-order moments can be used to count them, provided all modes have
      the same covariance matrix, and their multiplicity is not greater than data
      dimensionality. Examples of mode-counting and the determination of bimodal
      parameters are included.

PMID- 21869126
TI  - Decision making in context.
AB  - From a Bayesian decision theoretic framework, we show that the reason why the
      usual statistical approaches do not take context into account is because of the
      assumptions made on the joint prior probability function and because of the
      simplistic loss function chosen. We illustrate how the constraints sometimes
      employed by artificial intelligence researchers constitute a different kind of
      assumption on the joint prior probability function. We discuss a couple of loss
      functions which do take context into account and when combined with the joint
      prior probability constraint create a decision problem requiring a combinatorial
      state space search. We also give a theory for how probabilistic relaxation works
      from a Bayesian point of view.

PMID- 21869127
TI  - Application of the conditional population-mixture model to image segmentation.
AB  - The problem of image segmentation is considered in the context of a mixture of
      probability distributions. The segments fall into classes. A probability
      distribution is associated with each class of segment. Parametric families of
      distributions are considered, a set of parameter values being associated with
      each class. With each observation is associated an unobservable label, indicating
      from which class the observation arose. Segmentation algorithms are obtained by
      applying a method of iterated maximum likelihood to the resulting likelihood
      function. A numerical example is given. Choice of the number of classes, using
      Akaike's information criterion (AIC) for model identification, is illustrated.

PMID- 21869128
TI  - A facsimile-based graphics editing system by auxiliary mark recognition.
AB  - This paper describes a facsimile-based graphics editing system using handwritten
      mark recognition, and presents some experimental results with the system. In a
      manner different from usual graphics editors based on CRT displays and data
      tablets, only facsimiles are used as input and output devices in this system. As
      the first stage in processing, a graphic subject is first given as a set of line
      drawings and characters handwritten on a sheet of paper, and it is then input
      into the computer as a binary picture from a facsimile transmitter. Auxiliary
      editing information is input into the computer as handwritten marks or seal marks
      prepared on a separate sheet of paper. As the second stage, the marks are
      recognized and used to create a mark parameter list for the graphics editing.
      Third, referencing the mark parameter list, the graphics are expressed by using a
      set of graphic commands, and edited by the computer. Finally, a correct edited
      copy of the graphics is constructed by picture processing based on graphic
      commands, and it is output to a facsimile receiver. Very good results have been
      obtained for various kinds of hand-written graphics by using the system described
      here.

PMID- 21869129
TI  - Image design: generation of a prescribed image at the output of a band-limited
      system.
AB  - Image design involves determining the object distribution which produces a
      prescribed image at the output of a given imaging system. We solve the problem of
      generating two parallel lines at the output of an imaging system that is modeled
      by a linear band-limited system foliowed by a point nonlinearity of the
      hardlimiting type. It is shown that a solution always exists whatever the
      system's bandwidth. In principle, infinite two-line resolution is achievable. In
      practice, resolution much higher than the conventional resolution of the imaging
      system is possible.

PMID- 21869130
TI  - ATTENDING: Critiquing a Physician's Management Plan.
AB  - The ATTENDING system is designed to critique a physician's preoperative plan for
      anesthetic management. In undertaking to critique a physician's plan, ATTENDING
      differs from other medical decision making systems, which in effect attempt to
      tell a physician what to do. ATTENDING's approach may prove more acceptable
      clinically, and may avoid certain social, medical, and medicolegal drawbacks. To
      cri-tique a physician's plan, ATTENDING must confront three basic problems. 1) It
      must be able to explore flexibly all possible approaches for a patient's
      management. The formalism of an ''augmented decision network'' allows this. 2) It
      must be able to assess the relative risks and benefits of alternative approaches
      intelligently. A heuristic approach to risk analysis is outlined, based on three
      basic principles which are de-scribed in detail. 3) It must produce a potentially
      complex analysis which critiques the plan in focused, readable prose. This is
      facilitated by PROSENET, an approach which allows clean separation between the
      organization of the content of an analysis and its expression in English prose.

PMID- 21869131
TI  - Generating object descriptions for model retrieval.
AB  - A computer vision system is proposed, in which the recogni-tion of an object
      involves two interacting processes: model retrieval and model verification. The
      goal of the model retrieval process is to generate a proper structural
      description of the object in the input image, and use the description to retrieve
      candidate object models from the associative memory of the vision system. The
      present study explores one way of deriving such an object shape description from
      a single image. Regularity constraints and a preference rule are used to restrict
      the solutions to a preferred interpretation of geometric contours. Local
      interpretation is then propagated to neighboring regions. Through a proper
      control on the interaction between constraints and consistency checking, a rough
      object description in terms of visible surface orientations can be gener-ated. A
      computer vision system using this approach has been imple-mented and it is
      described in some details.

PMID- 21869132
TI  - Parsing and translation of (attributed) expansive graph languages for scene
      analysis.
AB  - In this paper, we suggest a class of (attributed) expansive graph grammars which
      generate languages contained in a graph family ?. It turns out that by means of
      node renumbering using a very effi-cient algorithm, any graph in ? can be
      converted into a standard form, which enables the use of related string
      representation for that graph to facilitate the syntax analysis. As a
      consequence, the syntax analysis of (attributed) expansive graph language is very
      efficient and almost like the parsing of tree languages. Furthermore, a syntax
      directed transla-tion can be established for mapping one (attributed) expansive
      graph language to another. Finally, since many relational graphs for scene
      analysis can be considered as belonging to these graph languages, the proposed
      graph grammar model appears to be quite attractive from the application point of
      view.

PMID- 21869133
TI  - Efficient recovery of shape from texture.
AB  - Witkin proposed a maximum likelihood model for the recovery of surface
      orientation from image texture. We develop two efficient algorithms for solving
      this shape from texture problem and compare the results of these algorithms with
      the algorithm described in [1].

PMID- 21869134
TI  - Inherent bias and noise in the hough transform.
AB  - Considering the Hough transformation as a linear imaging process recasts certain
      well-known problems, provides a useful vocab-ulary, and possibly indicates a
      source of applicable literature on the behavior of the Hough transformation in
      various forms of noise. A consideration of the analytic form of peaks in
      parameter space sets the stage for the idea of using complementary (negative)
      votes to cancel off-peak positive votes in parameter space, thus sharpening peaks
      and reducing bias.

PMID- 21869135
TI  - A Laser Time-of-Flight Range Scanner for Robotic Vision.
AB  - The requirements of three-dimensional scene analysis in support of vision driven
      robotic manipulation are such that direct range finding capabilities can greatly
      reduce the computational burden (time and complexity) for reliable determination
      of the placement and spatial extent of objects in the scene. This paper describes
      a laser time-of-flight range scanner capable of acquiring a reasonable rangepic
      of 64 * 64 spatial resolution in 4 s. However, at the current state of
      development, 100 samples/point are required to achieve a range accuracy of
      approxi-mately +/-? cm, with a scan time of 40 s. Returned signal amplitude de
      pendency is also apparent in the range determination, the dynamic range of
      intensity being considerable. Improved accuracy can be traded for tine. The
      vision/robotics laboratory environment within which the range scanner operates is
      briefly touched upon and some preliminary rangepic results presented.

PMID- 21869136
TI  - Pattern recognition experiments in the mandala/cosine domain.
AB  - The problem of recognition of objects in images is investigated from the
      simultaneous viewpoints of image bandwidth compression and automatic target
      recognition. A scenario is suggested in which recognition is implemented on
      features in the block cosine transform domain which is useful for data
      compression as well. While most image frames would be processed by the automatic
      recognition algorithms in the compressed domain without need for image
      reconstruction, this still allows for visual image classification of targets with
      poor recognition rates (by human viewing at the receiving terminal). It has been
      found that the Mandala sorting of the block cosine domain results in a more
      effective domain for selecting target identification parameters. Useful features
      from this Mandala/cosine domain are developed based upon correlation parameters
      and homogeneity measures which appear to successfully discriminate between
      natural and man-made objects. The Bhattacharyya feature discriminator is used to
      provide a 10:1 compression of the feature space for implementation of simple
      statistical decision surfaces (Gaussian and minimum distance classification).
      Imagery sensed in the visible spectra with a resolution of approximately 5-10 ft
      is used to illustrate the success of the technique on targets such as ships to be
      separated from clouds. A data set of 38 images is used for experimental
      verification with typical classification results ranging from the high 80's to
      low 90 percentile regions depending on the options choosen.

PMID- 21869137
TI  - Manipulation and presentation of multidimensional image data using the peano
      scan.
AB  - A fractal curve first discussed by Giuseppe Peano has useful statistical
      properties in image processing. The curve can act as a transform between a line
      and n-dimensional space retaining some of the spatially associative properties of
      the space. Applications of the curve include multispectral image display,
      compression in the color and spa-tial domain, classification, and color display.
      The technique enables the display of high quality color images on a frame store
      capable of displaying only 256 colors simultaneously. A logically ordered and
      complete set of colors for false color work can be selected. An im-provement in
      compression by about 3X for color images can be ob-tained by using this method in
      conjunction with an existing spatial compression technique. A simple algorithm
      for constructing the curves is shown.

PMID- 21869138
TI  - Chain coding with a hexagonal lattice.
AB  - This paper investigates the performance of chain code quantization of general
      curves using a hexagonal lattice structure, as a means of improving efficiency
      over the standard square lattice. Performance is first computed theoretically,
      assuming a generalization of grid-intersect quantization, and the curve to be
      quantized is assumed to be a straight line. An algorithm is then developed to
      perform chain coding using the hex lattice. Computer simulations were performed
      to evaluate hexagonal chain coding for a variety of curves, including circles of
      various curva-ture, straight lines, and a stochastic curve model. We find that
      the straight-line theory is substantiated for curves whose radius of curvature is
      roughly twice the lattice constant. For a given peak error in quanti-zation,
      hexagonal coding reduces the bit rate about 15 percent relative to the square
      lattice codes, and exhibits qualitative improvements in fidelity as well.

PMID- 21869139
TI  - Quad-trees, oct-trees, and k-trees: a generalized approach to recursive
      decomposition of euclidean space.
AB  - K-trees are developed as a K-dimensional analog of quad-trees and oct-trees. K
      trees can be used for modeling K-dimensional data. A fast algorithm is given for
      finding the boundary size of a K-dimensional object represented by a K-tree. For
      K considered as con-stant; the algorithm provides a method for computing the
      perimeter of a quad-tree encoded image or the surface area of an oct-tree encoded
      object in worst case time proportional to the number of nodes in the tree. This
      improves upon the expected-case linear-time method of Samet [10] for the
      perimeter problem. Our method has been implemented in Pascal, and a computational
      example is given.

PMID- 21869140
TI  - Multidimensional logical transforms.
AB  - This correspondence reviews the logical transform and pre-sents new theoretical
      and empirical developments. Novel extensions of the logical transform into spaces
      of three and four dimensions are de-scribed using the hexahedral and octahedral
      tessellations. These new tessellations are important in that they yield
      sufficiently compact neighborhoods to permit multidimensional cellular logic
      transforms to be carried out in real time by table lookup. Applications of
      logical transforms in these tessellations to data and image analysis are
      provided.

PMID- 21869141
TI  - Designing a handwriting reader.
AB  - Computer recognition of cursive handwriting is complisated by the lack of letter
      separation. In an attempt to gain insight on the cursive problem, the simpler
      problem of recognizing separated hand-written letters is addressed here. A warp
      based character matching technique is employed with dictionary lookup, using a 16
      000 word vocabulary. Cooperative users achieve high recognition accuracy with
      this on-line system, which is easily tailored to the individual. Possible
      extensions to cursive writing are discussed.

PMID- 21869142
TI  - A real-time automated visual inspection system for hot steel slabs.
AB  - This paper describes an inspection system designed to automatically detect and
      classify surface imperfections occurring on continuously cast hot steel slabs in
      a steel mill. The need to perform inspection at real-time throughput rates of 546
      Kpixels/s using off-the-shelf components has led to the development of a unique
      architecture and algorithm set. The segmentation operations are done in a high
      speed array processor front end. The imperfection classification is done in a
      mini-computer which uses statistical as well as syntactic/semantic classification
      techniques. The inspection system is currently undergoing evaluation in a steel
      mill.

PMID- 21869143
TI  - Identifying and locating surface defects in wood: part of an automated lumber
      processing system.
AB  - Continued increases in the cost of materials and labor make it imperative for
      furniture manufacturers to control costs by improved yield and increased
      productivity. This paper describes an Automated Lumber Processing System (ALPS)
      that employs computer tomography, optical scanning technology, the calculation of
      an optimum cutting strategy, and a computer-driven laser cutting device. While
      certain major hardware components of ALPS are already commercially available, a
      major missing element is the automatic inspection system needed to locate and
      identify surface defects on boards. This paper reports research aimed at
      developing such an inspection system. The basic strategy is to divide the digital
      image of a board into a number of disjoint rectangular regions and classify each
      independently. This simple procedure has the advantage of allowing an obvious
      parallel processing implementation. The study shows that measures of tonal and
      pattern related qualities are needed. The tonal measures are the mean, variance,
      skewness, and kurtosis of the gray levels. The pattern related measures are those
      based on cooccurrence matrices. In this initial feasibility study, these combined
      measures yielded an overall 88.3 percent correct classification on the eight
      defects most commonly found in lumber. To minimize the number of calculations
      needed to make the required classifications a sequential classifier is proposed.

PMID- 21869144
TI  - INSPECTOR: A Computer Vision System that Learns to Inspect Parts.
AB  - A computer vision inspection system has been developed that learns the difference
      between good and bad parts by being shown several identified good and bad parts.
      The model, formed during the training session, contains identifying points which
      are used for locating parts and inspection tests which apply only to pertinent
      regions of the part. Using the model, the system can distinguish between good
      parts and bad parts with an arbitrary number of defects. It can also learn to
      classify parts if it is shown the different parts during the training session.
      Examples of INSPECTOR inspecting industrial parts are shown.

PMID- 21869145
TI  - Precision of digital vision systems.
AB  - The precision of geometric features such as the centroid, area, perimeter, and
      orientation measured by a 2-D digital vision system is analyzed and tested
      experimentally. The digitizing error of various geometric features can be
      expressed in terms of the dimensionless perimeter of the object. As a result of
      this work, the sampling process can be simplified or eliminated. The analysis is
      also expanded to cover the 3-D digital vision systems.

PMID- 21869146
TI  - Integrated testing and algorithms for visual inspection of integrated circuits.
AB  - This paper deals with the integrated pre-cap testing of integrated circuits
      (IC's), defined as a simultaneous combination of electrical testing and of visual
      inspection using image analysis techniques. The emphasis is on image analysis
      models and algorithms for integrated testing of small and large defects. Two
      algorithms are presented for the analysis of visible and infrared imagery during
      electrical testing. Algorithm 1 matches bridges or subgraphs derived from the
      topological layout. Algorithm 2 computes a figure of merit for the IC from a
      fuzzy language description.

PMID- 21869147
TI  - Efficient 3-d object representations for industrial vision systems.
AB  - The representation of 3-D objects is an important step in solving many problems
      in scene analysis. One of the most successful techniques is that based on the
      surfaces of objects. We describe several methods for obtaining such surface
      representations from various types of intrinsic images. In particular, previous
      work is reviewed and an algorithm based on region growing is investigated in
      terms of its efficiency in segmenting a set of points in 3-D space into planar
      faces. Information on the neighborhood structure of the points in the form of a
      spatial proximity graph is used to direct the segmentation. Applications to
      industrial objects are demonstrated.

PMID- 21869148
TI  - GAGESIGHT: A Computer Vision System for Automatic Inspection of Instrument
      Gauges.
AB  - GAGESIGHT is a computer vision system recently integrated into production which
      demonstrates new flexibility in production automation technology. The vision
      algorithm accommodates significant misregistration in the position and
      orientation of objects, and adjusts process control parameters accordingly. The
      GAGESIGHT system is easily reconfigured for inspecting new types of objects by
      executing a teach program, and responding to a few instructions at an interactive
      display console. GAGESIGHT, intially intended for the automatic inspection and
      assembly of pointers and other components to instrument gauges, is finding new
      applications as well since the approach employed makes few assumptions regarding
      the objects being viewed.

PMID- 21869149
TI  - Gauge inspection using hough transforms.
AB  - An automatic method of inspecting the scaling accuracy of needle-type instrument
      gauges using a two-stage Hough transform technique is described. The system
      measures and verifies the relative accuracy of a gauge's response to a specified
      set of analog input signals. The method does not require that the gauge's
      position, orientation, or size be known a priori and the algorithm is very
      suitable for high-speed hardware implementation.

PMID- 21869150
TI  - Automatic inspection system for printed circuit boards.
AB  - The purpose of this correspondence is to present problems and methods in
      automating visual inspection of printed circuit boards (PCB's). Vertical and
      diagonal illumination are useful in detecting PCB patterns correctly. An
      algorithm comparing local features of the patterns to be inspected with those of
      the pattern to be referenced is proposed. An inspection system using developed
      technologies is also described.

PMID- 21869151
TI  - Error analysis of surface normals determined by radiometry.
AB  - Surface normals can be computed from three images of a workpiece taken under
      three distinct lighting conditions without requiring surface continuity.
      Radiometric methods are susceptible to systematic errors such as: errors in the
      measurement of light source orientations; mismatched light source irradiance;
      detector nonlinearity; the presence of specular reflection or shadows; the
      spatial and spectral distribution of incident light; surface size, material, and
      microstructure; and the length and properties of the light source to target path.
      Typically, a 1 degrees  error in surface orientation of a Lambertian workpiece is
      caused by a 1 percent change in image intensity due to variations in incident
      light intensity or a 1 degrees  change in orientation of a collimated light
      source. Tests on a white nylon sphere indicate that by using modest error
      prevention and calibration schemes, surface angles off the camera axis can be
      computed within 5 degrees , except at edge pixels. Equations for the sensitivity
      of surface normals to major error sources have been derived. Results of surface
      normal estimation and edge extraction experiments on various non-Lambertian and
      textured workpieces are also presented.

PMID- 21869152
TI  - Recognition of agricultural objects by shape.
AB  - It is desired to enhance the outline of agricultural contraband in X-ray images
      of passenger luggage. Agricultural contraband consists of fruit, meats, animals,
      and plants. We suggest most contraband can be distinguished from other material
      by an elliptic, rather than rectangular, cross section. An algorithm is proposed
      to recognize such cross section using the erosion of the absolute gradient of the
      image. Only local convolution calculations are required. This algorithm is tested
      on a number of computed images as well as on X-ray images of model objects,
      isolated contraband, and contraband contained and obscured in baggage. The effect
      of image noise, object size, orientation, and obscuration is tested. It is shown
      that the proposed algorithm successfully enhances the outlines of desired items
      as small as 1-2 cm (7-11 pixels) to the exclusion of remaining material under the
      conditions expected in actual use.

PMID- 21869153
TI  - Viewer independent shape recognition.
AB  - An important problem in vision is to detect the presence of a known rigid 3-D
      object. The general 3-D object recognition task can be thought of as building a
      description of the object that must have at least two parts: 1) the internal
      description of the object itself (with respect to an object-centered frame); and
      2) the transformation of the object-centered frame to the viewer-centered (image)
      frame. The reason for this decomposition is parsimony: different views of the
      object should have minimal impact on its description. This is achieved by
      factoring the object's description into two sets of parameters, one which is view
      independent (the object-centered component) and one which is view-varying (the
      viewing transformation). Often a description of the object is known beforehand
      and the task reduces to finding the objectframe to viewer-frame transformation.
      This paper describes a method for handling this case: a known object is detected
      by finding changes in orientation, translation, and scale of the object from its
      canonical description. The method is a Hough technique and has the characteristic
      insensitivity to occlusion and noise.

PMID- 21869154
TI  - On closing the fourier descriptor presentation.
AB  - A numerical method is presented to close the truncated Fourier descriptor
      presentation of a closed curve.

PMID- 21869155
TI  - On the use of I-divergence for generating distribution approximations.
AB  - The existence of an upper bound for the error probability as a function of I
      divergences between an original and an approximating distribution is proved. Such
      a bound is shown to be a monotonic nondecreasing function of the I-divergences,
      reaching the Bayes error probability when they vanish. It has been shown that if
      the closeness between the original and approximating distributions is assessed by
      the probability of error associated with a particular two-class recognition
      problem in which those functions are the class conditional distributions, then
      the best upper bound for such probability is ? regardless of the value of the I
      divergences between them. Approaching the approximation problem from a rather
      different viewpoint, this correspondence considers the problem of a two-class
      discrete measurement classification where the original distributions are replaced
      by approximations, and its effects on the probability of error. The corresponding
      analysis is presented in detail.

PMID- 21869156
TI  - Predicting the required number of training samples.
AB  - In this paper a criterion which measures the quality of the estimate of the
      covariance matrix of a multivariate normal distribution is developed. Based on
      this criterion, the necessary number of training samples is predicted.
      Experimental results which are used as a guide for determining the number of
      training samples are included.

PMID- 21869157
TI  - Scale preserving smoothing of polygons.
AB  - A smoother version of a polygon ? is defined as a polygon which approximates ?
      according to a given criterion and which simultaneously has no more edges than ?
      itself. In this paper, a scale preserving smoothing algorithm is presented. The
      input to the algorithm is a polygon ? and the output is its smoothed version ?.
      ?, which contains all the scale information that ? contains, is called the linear
      minimum perimeter polygon (LMPP) of ? within a tolerance of. Using the quantity
      the degree of with ? approximates ? can be controlled. From the LMPP a
      representation for a polygon approximating ? can be procured, which is invariant
      to scale and translation changes. Examples of smoothing maps and characters have
      been presented.

PMID- 21869158
TI  - Nonparametric discriminant analysis.
AB  - A nonparametric method of discriminant analysis is proposed. It is based on
      nonparametric extensions of commonly used scatter matrices. Two advantages result
      from the use of the proposed nonparametric scatter matrices. First, they are
      generally of full rank. This provides the ability to specify the number of
      extracted features desired. This is in contrast to parametric discriminant
      analysis, which for an L class problem typically can determine at most L 1
      features. Second, the nonparametric nature of the scatter matrices allows the
      procedure to work well even for non-Gaussian data sets. Using the same basic
      framework, a procedure is proposed to test the structural similarity of two
      distributions. The procedure works in high-dimensional space. It specifies a
      linear decomposition of the original data space in which a relative indication of
      dissimilarity along each new basis vector is provided. The nonparametric scatter
      matrices are also used to derive a clustering procedure, which is recognized as a
      k-nearest neighbor version of the nonparametric valley seeking algorithm. The
      form which results provides a unified view of the parametric nearest mean
      reclassification algorithm and the nonparametric valley seeking algorithm.

PMID- 21869159
TI  - The asymptotic optimal frequency domain filter for edge detection.
AB  - In an earlier paper by Shanmugam, Dickey, and Green, an edge detection filter was
      derived which maximized the energy within a specified interval about an edge
      feature. The initial expression of this filter involved a prolate spheroidal wave
      function. However, a careful analysis of the application of an asymptotic
      approximation to this function uncovered a major dimensional error. The corrected
      derivation of the asymptotic optimal filter forms the subject of this paper. To
      verify the results, the filter found is compared to a similar filter developed
      independently by Marr and Hildreth.

PMID- 21869160
TI  - Some recent results in heuristic search theory.
AB  - The paper summarizes recent analytical investigations of the mathematical
      properties of heuristics and their influence on the performance of common search
      techniques. The results are reported without proofs together with discussions of
      motivations and interpretations. The highlights include the following: the
      optimality of A*; relations between the precision of the heuristic estimates and
      the average complexity of the search; comparisons of the average complexities of
      A* and BACKTRACKING; procedures for comparing and combining nonadmissible
      heuristic functions; the influence of the weight w (in f = (l - w) g + wh) on the
      complexity of A*; the pruning power of alphabeta, SSS*, and SCOUT; the effect of
      successor ordering on search complexity, and the effect of search depth of the
      quality of decisions in game-playing.

PMID- 21869161
TI  - Uniqueness and estimation of three-dimensional motion parameters of rigid objects
      with curved surfaces.
AB  - Two main results are established in this paper. First, we show that seven point
      correspondences are sufficient to uniquely determine from two perspective views
      the three-dimensional motion parameters (within a scale factor for the
      translations) of a rigid object with curved surfaces. The seven points should not
      be traversed by two planes with one plane containing the origin, nor by a cone
      containing the origin. Second, a set of ''essential parameters'' are introduced
      which uniquely determine the motion parameters up to a scale factor for the
      translations, and can be estimated by solving a set of linear equations which are
      derived from the correspondences of eight image points. The actual motion
      parameters can subsequently be determined by computing the singular value
      decomposition (SVD) of a 3*3 matrix containing the essential parameters.

PMID- 21869162
TI  - Curvature and tangential deflection of discrete arcs: a theory based on the
      commutator of scatter matrix pairs and its application to vertex detection in
      planar shape data.
AB  - This paper introduces a new theory for the tangential deflection and curvature of
      plane discrete curves. Our theory applies to discrete data in either rectangular
      boundary coordinate or chain coded formats: its rationale is drawn from the
      statistical and geometric properties associated with the eigenvalue-eigenvector
      structure of sample covariance matrices. Specifically, we prove that the nonzero
      entry of the commutator of a piar of scatter matrices constructed from discrete
      arcs is related to the angle between their eigenspaces. And further, we show that
      this entry is-in certain limiting cases-also proportional to the analytical
      curvature of the plane curve from which the discrete data are drawn. These
      results lend a sound theoretical basis to the notions of discrete curvature and
      tangential deflection; and moreover, they provide a means for computationally
      efficient implementation of algorithms which use these ideas in various image
      processing contexts. As a concrete example, we develop the commutator vertex
      detection (CVD) algorithm, which identifies the location of vertices in shape
      data based on excessive cummulative tangential deflection; and we compare its
      performance to several well established corner detectors that utilize the
      alternative strategy of finding (approximate) curvature extrema.

PMID- 21869163
TI  - A piecewise linear approximation based on a statistical model.
AB  - A statistical model is introduced and then, based on it, a piecewise linear
      approximation algorithm of linear computational complexity is presented. The
      advantages of the algorithm are proved experimentally in small sample cases and
      theoretically in the large sample case. The paper is closed with a discussion on
      some possible extensions.

PMID- 21869164
TI  - A Fast Correlation Method for Scale-and Translation-Invariant Pattern
      Recognition.
AB  - A size- and position-invariant description of an image function can be obtained
      via the absolute value of the Mellin transform of its Fourier amplitude spectrum.
      If the transform is implemented on a digital computer via a discrete Fourier
      Mellin transform, these exact invariances are not preserved due to sampling-and
      border-effects. In this paper these effects are discussed, and an alternative
      correlation method is proposed. The method consists of calculating the normalized
      absolute magnitude of the discrete Fourier transform (DFT) of the image function
      (which gives invariance to translation and multiplicative amplitude changes) and
      a subsequent logarithmic distortion in x- and y- direction, which converts
      scaling to translation. Two such transforms are compared by calculating the
      normalized Euclidean distances between both for all possible relative shifts
      along the main diagonal. If, for some shift, the distance has a minimum below a
      similarity threshold, the underlying image functions will probably differ only by
      translation and scaling. The magnitude of this shift is related to the scale
      factor between the objects. Good separation between similar and nonsimilar
      objects is possible if two size criteria imposed by the DFT are met: the total
      object size must not exceed N/4 (N is the number of image points in each
      dimension), and object details have to be larger than about 4 image points. As a
      consequence, N increases with object complexity and desired scale range.

PMID- 21869165
TI  - Digital step edges from zero crossing of second directional derivatives.
AB  - We use the facet model to accomplish step edge detection. The essence of the
      facet model is that any analysis made on the basis of the pixel values in some
      neighborhood has its final authoritative interpretation relative to the
      underlying gray tone intensity surface of which the neighborhood pixel values are
      observed noisy samples. With regard to edge detection, we define an edge to occur
      in a pixel if and only if there is some point in the pixel's area having a
      negatively sloped zero crossing of the second directional derivative taken in the
      direction of a nonzero gradient at the pixel's center. Thus, to determine whether
      or not a pixel should be marked as a step edge pixel, its underlying gray tone
      intensity surface must be estimated on the basis of the pixels in its
      neighborhood. For this, we use a functional form consisting of a linear
      combination of the tensor products of discrete orthogonal polynomials of up to
      degree three. The appropriate directional derivatives are easily computed from
      this kind of a function. Upon comparing the performance of this zero crossing of
      second directional derivative operator with the Prewitt gradient operator and the
      Marr-Hildreth zero crossing of the Laplacian operator, we find that it is the
      best performer; next is the Prewitt gradient operator. The Marr-Hildreth zero
      crossing of the Laplacian operator performs the worst.

PMID- 21869166
TI  - Extremes in the complexity of computing metric distances between partitions.
AB  - Day [3] describes an analytical model of minimum-length sequence (MLS) metrics
      measuring distances between partitions of a set. By selecting suitable values of
      model coordinates, a user may identify within the model that metric most
      appropriate to his classification application. Users should understand that
      within the model similar metrics may nevertheless exhibit extreme differences in
      their computational complexities. For example, the asymptotic time complexities
      of two MLS metrics are known to be linear in the number of objects being
      partitioned; yet we establish below that the computational problem for a closely
      related MLS metric is NP-complete.

PMID- 21869167
TI  - Testing for uniformity in multidimensional data.
AB  - Testing for uniformity in multidimensional data is important in exploratory
      pattern analysis, statistical pattern recognition, and image processing. The goal
      of this paper is to determine whether the data follow the uniform distribution
      over some compact convex set in K-dimensional space, called the sampling window.
      We first provide a simple, computationally efficient method for generating a
      uniformly distributed sample over a set which approximates the convex hul of the
      data. We then test for uniformity by comparing this generated sample to the data
      by using Friedman-Rafsky's minimal spanning tree (MST) based test. Experiments
      with both simulated and real data indicate that this MST-based test is useful in
      deciding if data are uniform.

PMID- 21869168
TI  - K-means-type algorithms: a generalized convergence theorem and characterization
      of local optimality.
AB  - The K-means algorithm is a commonly used technique in cluster analysis. In this
      paper, several questions about the algorithm are addressed. The clustering
      problem is first cast as a nonconvex mathematical program. Then, a rigorous proof
      of the finite convergence of the K-means-type algorithm is given for any metric.
      It is shown that under certain conditions the algorithm may fail to converge to a
      local minimum, and that it converges under differentiability conditions to a Kuhn
      Tucker point. Finally, a method for obtaining a local-minimum solution is given.

PMID- 21869169
TI  - EMERGE-A Data-Driven Medical Decision Making Aid.
AB  - EMERGE is an expert system designed as a medical decision making aid. It is
      machine-independent, and is implemented in standard Pascal. It has modest memory
      requirements, and can operate on a microcomputer. EMERGE is rule-based, and its
      initial application is the analysis of chest pain in the emergency room. The
      knowledge base is maintained separately from the consultation program. Thus the
      application area can be changed without any modification to the software. This
      paper describes the control structures and rule searching procedures used in
      EMERGE.

PMID- 21869170
TI  - Planning collision-free paths for robotic arm among obstacles.
AB  - A theory for planning collision-free paths of a moving object among obstacles is
      described. Using the concepts of state space and rotation mapping, the
      relationship between the positions and the corresponding collision-free
      orientations of a moving object among obstacles is represented as some set of a
      state space. This set is called the rotation mapping graph (RMG) of that object.
      The problem of finding collision-free paths for an object translating and
      rotating among obstacles is thus transformed to that of considering the
      connectivity of the RMG. Since the connectivity of the graph can be solved by
      topological methods, the problem of planning collision-free paths is easily
      solved in theory. Using this theory, a topological method for planning collision
      free paths of a rod-object translating and rotating among obstacles is presented.
      If a nonrigid robotic arm is viewed as a composite rod with some degrees of
      freedom, the planning of collision-free paths of a robotic arm can be solved in a
      similar way to a rod.

PMID- 21869171
TI  - Diffuse edge fitting and following: a location-adaptive approach.
AB  - The detection and tracing of edges of varying diffusion is a problem of
      importance in image analysis. In particular, it is of interest for the
      segmentation of meteorological and physiological pictures where the boundaries of
      objects are possibly not well defined or are obscured to a varying extent by
      noise. We present an edge detection and line fitting procedure which ascribes a
      direction, a measure of gradient, and quality of fit to the edge within a square
      segment of a controlled size or ''scope.'' To detect and fit edges to diffuse
      objects the scope is adaptively altered based on the confidence of fit to permit
      tracing of the object's boundary. We discuss predictor-corrector procedures for
      performing this edge tracing where predicted and calculated lines and confidences
      are used to generate a better fitting line. The performance of the procedures is
      demonstrated using both synthetic and satellite meteorological images.

PMID- 21869172
TI  - Fourier coding of image boundaries.
AB  - A transform coding scheme for closed image boundaries on a plane is described.
      The given boundary is approximated by a series of straight line segments.
      Depending on the shape, the boundary is represented by the (x-y) coordinates of
      the endpoints of the line segments or by the magnitude of the successive radii
      vectors that are equispaced in angle around the given boundary. Due to the
      circularity present in the data, the discrete Fourier transform is used to
      exactly decorrelate the finite boundary data. By fitting a Gaussian circular
      autoregressive model to represent the boundary data, estimates of the variances
      of the Fourier coefficients are obtained. Using the variances of the Fourier
      coefficients and the MAX quantizer, the coding scheme is implemented. The scheme
      is illustrated by an example.

PMID- 21869173
TI  - A syntactic approach for handwritten mathematical formula recognition.
AB  - Mathematical formulas are good examples of two-dimensional patterns as well as
      pictures or graphics. The use of syntactic methods is useful for interpreting
      such complex patterns. In this paper we propose a system for the interpretation
      of 2-D mathematic formulas based on a syntactic parser. This system is able to
      recognize a large class of 2-D mathematic formulas written on a graphic tablet.
      It starts the parsing by localization of the ''principal'' operator in the
      formula and attempts to partition it into subexpressions which are similarly
      analyzed by looking for a starting character. The generalized parser used in the
      system has been developed in our group for continuous speech recognition and
      picture interpretation.

PMID- 21869174
TI  - A similarity measure between patterns with nonindependent attributes.
AB  - A generalized version of a set-theoretical measure for obtaining similarities
      between patterns with nonindependent attributes is presented. The dependence here
      is given by the pairwise correlation. Since the proposed measure needs no
      assumption of attribute independence, the resulting similarity values can reflect
      directly the relationships between the attributes.

PMID- 21869175
TI  - Nonparametric data reduction.
AB  - A nonparametric data reduction technique is proposed. Its goal is to select
      samples that are ''representative'' of the entire data set. The technique is
      iterative and is based on the use of a criterion function and nearest neighbor
      density estimates. Experiments are presented to demonstrate the algorithm.

PMID- 21869176
TI  - Game theoretical pattern recognition: application to imperfect noncooperative
      learning and to multiclass classification.
AB  - This paper studies in theory, and gives a solution to, the following concerns
      which may eventually be simultaneous: 1) obtain alternative classification
      decisions, ranked by some decreasing order of class membership probabilities; 2)
      imperfect teacher at the learning stage, or effects of labeling errors due to
      unsupervised learning by clustering; 3) noncooperative teacher, manipulating the
      a priori class probabilities; 4) unknown a priori class probabilities. These
      requirements are taken into account by considering a game between the recognition
      system and the teacher, in a game theoretical framework. Both players will
      ultimately select ''mixed strategies,'' which are probability distributions over
      the set of N alternative pattern classes, determined for each feature vector to
      be classified. This solution concept is interpreted in terms of the requirements
      1)-4); numerical algorithms, as well as numerical examples are given with their
      solutions.

PMID- 21869177
TI  - A Note on Sugihara's Claim.
AB  - This correspondence debates a theorem formulated by K. Sugihara in a recent
      publication. The theorem deals with the mathematical structures of line drawings,
      and serves as a basis for a substantial part of the paper. This note claims that
      the theorem as formulated is not valid. The claim is substantiated by a
      counterexample.

PMID- 21869178
TI  - An intelligent control strategy for computer consultation.
AB  - Expert consultant systems often perform computations on a directed graph of
      associated propositions. Each proposition is represented by a node. Edges
      connecting these nodes are associated with rules which organize the propositions
      into antecedent/consequent relationships. A node may be assigned a value through
      the edges that bind it to its antecedents. Various strategies are employed to
      determine assignment sequences that result in efficient computer consultation.
      One such strategy, the merit system, has been successfully implemented in Battle,
      an expert consultant system for the Marine Corps. The merit strategy enables
      Battle to focus the consultation process on the most appropriate questions. The
      merit system, originally defined for logical functions in the Multiple program,
      has been extended to the Mycin style of propagation and to the method of
      subjective Bayesian assignments used by Prospector. A procedure for merit
      calculations with any differentiable, real-valued assignment function is
      presented. Our experience has shown that merit values provide an efficient flow
      of control for expert consultation.

PMID- 21869179
TI  - Shape matching of two-dimensional objects.
AB  - In this paper we present results in the areas of shape matching of nonoccluded
      and occluded two-dimensional objects. Shape matching is viewed as a ''segment
      matching'' problem. Unlike the previous work, the technique is based on a
      stochastic labeling procedure which explicitly maximizes a criterion function
      based on the ambiguity and inconsistency of classification. To reduce the
      computation time, the technique is hierarchical and uses results obtained at low
      levels to speed up and improve the accuracy of results at higher levels. This
      basic technique has been extended to the situation where various objects
      partially occlude each other to form an apparent object and our interest is to
      find all the objects participating in the occlusion. In such a case several
      hierarchical processes are executed in parallel for every object participating in
      the occlusion and are coordinated in such a way that the same segment of the
      apparent object is not matched to the segments of different actual objects. These
      techniques have been applied to two-dimensional simple closed curves represented
      by polygons and the power of the techniques is demonstrated by the examples taken
      from synthetic, aerial, industrial and biological images where the matching is
      done after using the actual segmentation methods.

PMID- 21869180
TI  - A representation for shape based on peaks and ridges in the difference of low
      pass transform.
AB  - This paper defines a multiple resolution representation for the two-dimensional
      gray-scale shapes in an image. This representation is constructed by detecting
      peaks and ridges in the difference of lowpass (DOLP) transform. Descriptions of
      shapes which are encoded in this representation may be matched efficiently
      despite changes in size, orientation, or position. Motivations for a multiple
      resolution representation are presented first, followed by the definition of the
      DOLP transform. Techniques are then presented for encoding a symbolic structural
      description of forms from the DOLP transform. This process involves detecting
      local peaks and ridges in each bandpass image and in the entire three-dimensional
      space defined by the DOLP transform. Linking adjacent peaks in different bandpass
      images gives a multiple resolution tree which describes shape. Peaks which are
      local maxima in this tree provide landmarks for aligning, manipulating, and
      matching shapes. Detecting and linking the ridges in each DOLP bandpass image
      provides a graph which links peaks within a shape in a bandpass image and
      describes the positions of the boundaries of the shape at multiple resolutions.
      Detecting and linking the ridges in the DOLP three-space describes elongated
      forms and links the largest peaks in the tree. The principles for determining the
      correspondence between symbols in pairs of such descriptions are then described.
      Such correspondence matching is shown to be simplified by using the
      correspondence at lower resolutions to constrain the possible correspondence at
      higher resolutions.

PMID- 21869181
TI  - Local shading analysis.
AB  - Local analysis of image shading, in the absence of prior knowledge about the
      viewed scene, may be used to provide information about the scene. The following
      has been proved. Every image point has the same image intensity and first and
      second derivatives as the image of some point on a Lambertian surface with
      principal curvatures of equal magnitude. Further, if the principal curvatures are
      assumed to be equal there is a unique combination of image formation parameters
      (up to a mirror reversal) that will produce a particular set of image intensity
      and first and second derivatives. A solution for the unique combination of
      surface orientation, etc., is presented. This solution has been extended to
      natural imagery by using general position and regional constraints to obtain
      estimates of the following: ? surface orientation at each image point; ? the
      qualitative type of the surface, i.e., whether the surface is planar,
      cylindrical, convex, concave, or saddle; ? the illuminant direction within a
      region. Algorithms to recover illuminant direction and estimate surface
      orientation have been evaluated on both natural and synthesized images, and have
      been found to produce useful information about the scene.

PMID- 21869182
TI  - Edge location to subpixel values in digital imagery.
AB  - A new method for locating edges in digital data to subpixel values and which is
      invariant to additive and multiplicative changes in the data is presented. For
      one-dimensional edge patterns an ideal edge is fit to the data by matching
      moments. It is shown that the edge location is related to the so-called
      ''Christoffel numbers.'' Also presented is the study of the effect of additive
      noise on edge location. The method is extended to include two-dimensional edge
      patterns where a line equation is derived to locate an edge. This in turn is
      compared with the standard Hueckel edge operator. An application of the new edge
      operator as an edge detector is also provided and is compared with Sobel and
      Hueckel edge detectors in presence and absence of noise.

PMID- 21869183
TI  - Contextual template matching: a distance measure for patterns with hierarchically
      dependent features.
AB  - Contextual template matching refers to situations where the feature sets of the
      two templates under consideration may not be identical, but are rather contingent
      on the context within which these templates are observed. This paper addresses
      context-dependent template matching where the relevancy of certain features to a
      given object is contingent on the value of higher level features. In such
      situations portions of the patterns for two objects X and Y may not be
      comparable, and therefore classical distance measures are not applicable. A
      framework for describing pattern spaces with hierarchically dependent features
      named conditional pattern spaces (CPS)-is presented, and a distance measure for
      comparing objects in a CPS is developed and illustrated on archaeological
      objects. This measure satisfies several desired properties of distance measures,
      such as the metric requirements.

PMID- 21869184
TI  - Fast computation of the difference of low-pass transform.
AB  - This paper defines the difference of low-pass (DOLP) transform and describes a
      fast algorithm for its computation. The DOLP is a reversible transform which
      converts an image into a set of bandpass images. A DOLP transform is shown to
      require O(N2) multiplies and produce O(N log(N)) samples from an N sample image.
      When Gaussian low-pass filters are used, the result is a set of images which have
      been convolved with difference of Gaussian (DOG) filters from an exponential set
      of sizes. A fast computation technique based on ''resampling'' is described and
      shown to reduce the DOLP transform complexity to O(N log(N)) multiplies and O(N)
      storage locations. A second technique, ''cascaded convolution with expansion,''
      is then defined and also shown to reduce the computational cost to O(N log(N))
      multiplies. Combining these two techniques yields an algorithm for a DOLP
      transform that requires O(N) storage cells and requires O(N) multiplies.

PMID- 21869185
TI  - Compact region extraction using weighted pixel linking in a pyramid.
AB  - This correspondence describes a method of image segmentation based on a
      ''pyramid'' of reduced-resolution versions of the image. It defines link
      strengths between pixels at adjacent levels of the pyramid, based on proximity
      and similarity, and iteratively recomputes the pixel values and adjusts the link
      strengths. After a few iterations, the strengths stabilize, and the links that
      remain strong define subtrees of the pyramid; the leaves of each tree are the
      pixels belonging to a compact (piece of a) homogeneous region in the image.

PMID- 21869186
TI  - Extracting compact objects using linked pyramids.
AB  - This correspondence describes a method of extracting compact regions from images
      using three multiresolution (''pyramid'') representations of image features. The
      method makes use of a gray-level pyramid in which linking of similar nodes at
      successive levels smooths the image into uniform regions; an edge pyramid in
      which linking of similarly oriented edge elements serves to delineate the
      boundaries of the detected regions; and a ''surroundedness'' pyramid in which
      pixels surrounded by edges are detected.

PMID- 21869187
TI  - Entropy-based texture analysis in the spatial frequency domain.
AB  - An approach which uses regional entropy measures in the spatial frequency domain
      for texture discrimination is presented. The measures provide texture
      discriminating information independent of that contained in the usual summed
      energy within based frequency domain features. Performance of the entropy
      features as measured by a between-to-within-class scatter criterion is comparable
      to that of traditional frequency domain features and gray level co-occurrence
      contrast features. A method of frequency scaling is introduced to enable the
      comparison of texture samples of different subimage size. The resulting regional
      entropy measures are subimage size-invariant subject to certain constraints which
      arise from properties of the discrete Fourier transform.

PMID- 21869188
TI  - Space and time efficient virtual quadtress.
AB  - The quadtree has recently become a major data structure in image processing. This
      correspondence investigates ways in which quadtrees may be efficiently stored as
      a forest of quadtrees and as a new structure we call a compact quadtree. These
      new structures are called virtual quadtrees because the basic operations we
      expect to perform in moving about within a quadtree can also be performed on the
      new representations. Space and time efficiency are investigated and it is shown
      these new structures often given an improvement in both.

PMID- 21869189
TI  - Image segmentation: a comment on ''studies in global and local histogram-guided
      relaxation algorithms''.

PMID- 21869190
TI  - A tree-matching algorithm based on node splitting and merging.
AB  - An algorithm that computes the best matching of two trees is described. The
      degree of mismatch, i.e., the distance, is measured in terms of the number of
      node splitting and merging operations required. The proposed tree distance is a
      more appropriate measurement of structural defonnation than the tree distance
      measure in terms of the number of insertions, deletions, and substitutions of
      tree nodes, as defined in previous studies. An algorithm that uses a divide-and
      conquer strategy is presented. The analysis shows that the time complexity is
      O(NM2) where N and Al are the number of nodes of the two trees, respectively. The
      algorithm has been implemented on a VAX 11/780.

PMID- 21869191
TI  - Authors'Reply.

PMID- 21869192
TI  - Tactile recognition and localization using object models: the case of polyhedra
      on a plane.
AB  - This paper discusses how data from multiple tactile sensors may be used to
      identify and locate one object, from among a set of known objects. We use only
      local information from sensors: 1) the position of contact points and 2) ranges
      of surface normals at the contact points. The recognition and localization
      process is structured as the development and pruning of a tree of consistent
      hypotheses about pairings between contact points and object surfaces. In this
      paper, we deal with polyhedral objects constrained to lie on a known plane, i.e.,
      having three degrees of positioning freedom relative to the sensors. We
      illustrate the performance of the algorithm by simulation.

PMID- 21869193
TI  - Dynamic quantization: two adaptive data structures for multidimensional spaces.
AB  - Two new data structures are defined for use in multidimensional histogramming.
      Their purpose is to cover a parameter space with a limited number of histogram
      bins so that fine precision is maintained where it is needed. The original
      motivation for these data structures was to implement Hough-like transforms in
      high-dimensional parameter spaces. The two data structures share the ability to
      adapt to distributions that change with time.

PMID- 21869194
TI  - The converging squares algorithm: an efficient method for locating peaks in
      multidimensions.
AB  - The converging squares algorithm is a method for locating peaks in sampled data
      of two dimensions or higher. There are two primary advantages of this algorithm
      over conventional methods. First, it is robust with respect to noise and data
      type. There are no empirical parameters to permit adjustment of the process, so
      results are completely objective. Second, the method is computationally
      efficient. The inherent structure of the algorithm is that of a resolution
      pyramid. This enhances computational efficiency as well as contributing to the
      quality of noise immunity of the method. The algorithm is detailed for two
      dimensional data, and is described for three-dimensional data. Quantitative
      comparisons of computation are made with two conventional peak picking methods.
      Applications to biomedical image analysis, and for industrial inspection tasks
      are discussed.

PMID- 21869195
TI  - An extremum principle for shape from contour.
AB  - An extremum principle is developed that determines three-dimensional surface
      orientation from a two-dimensional contour. The principle maximizes the ratio of
      the area to the square of the perimeter, a measure of the compactness or symmetry
      of the three-dimensional surface. The principle interprets regular figures
      correctly and it interprets skew symmetries as oriented real symmetries. The
      maximum likelihood method approximates the principle on irregular figures, but we
      show that it consistently overestimates the slant of an ellipse.

PMID- 21869196
TI  - Parallel Parsing Algorithms and VLSI Implementations for Syntactic Pattern
      Recognition.
AB  - Earley's algorithm has been commonly used for the parsing of general context-free
      languages and the error-correcting parsing in syntactic pattern recognition. The
      time complexity for parsing is 0(n3). This paper presents a parallel Earley's
      recognition algorithm in terms of an ''X*'' operator. By restricting the input
      context-free grammar to be ?-free, the parallel algorithm can be executed on a
      triangular-shape VLSI array. This array system has an efficient way of moving
      data to the right place at the right time. Simulation results show that this
      system can recognize a string with length n in 2n + 1 system time. We also
      present a parallel parse-extraction algorithm, a complete parsing algorithm, and
      an error-correcting recognition algorithm. The parallel complete parsing
      algorithm has been simulated on a processor array which is similar to the
      triangular VLSI array. For an input string of length n the processor array will
      give the correct right-parse at system time 2n + 1 if the string is accepted. The
      error-correcting recognition algorithm has also been simulated on a triangular
      VLSI array. This array recognizes an erroneous string of length n in time 2n + 1
      and gives the correct error count. These parallel algorithms are especially
      useful for syntactic pattern recognition.

PMID- 21869197
TI  - An optimal global nearest neighbor metric.
AB  - A quadratic metric dAO (X, Y) =[(X - Y)T AO(X - Y)]? is proposed which minimizes
      the mean-squared error between the nearest neighbor asymptotic risk and the
      finite sample risk. Under linearity assumptions, a heuristic argument is given
      which indicates that this metric produces lower mean-squared error than the
      Euclidean metric. A nonparametric estimate of Ao is developed. If samples appear
      to come from a Gaussian mixture, an alternative, parametrically directed distance
      measure is suggested for nearness decisions within a limited region of space.
      Examples of some two-class Gaussian mixture distributions are included.

PMID- 21869198
TI  - Visual and conceptual hierarchy: a paradigm for studies of automated generation
      of recognition strategies.
AB  - The purpose of this correspondence is to show the design considerations in the
      choice of mechanisms when a flexible querysystem of visual scenes is being
      constructed. More concretely, the issues are: ? flexibility in adding new
      information to the knowledge base; ? power of inferencing; ? avoiding unnecessary
      generation of hypotheses where a great deal of image processing has to be
      perfected in order to test it; ? having the power of automatic generation of
      recognition strategies.

PMID- 21869199
TI  - A theory for invariant object recognition in the frontoparallel plane.
AB  - We suggest a new computational theory for position, size, and orientation
      invariant recognition of planar gray-scale forms in frontoparallel view. The
      theory employs a spatial-frequency representation which approximates the complex
      logarithmic conformally mapped Wigner distribution of a gray-scale image. Our
      discussion emphasizes the theoretical significance, method of computation, and
      practical utility of this powerful new representation for image pattern
      recognition.

PMID- 21869200
TI  - Incremental acquisition of a three-dimensional scene model from images.
AB  - We describe the current state of the 3-D Mosaic project, whose goal is to
      incrementally acquire a 3-D model of a complex urban scene from images. The
      notion of incremental acquisition arises from the observations that 1) single
      images contain only parfial information about a scene, 2) complex images are
      difficult to fully interpret, and 3) different features of a given scene tend to
      be easier to extract in different images because of differences in viewpoint and
      lighting conditions. In our approach, multiple images of the scene are
      sequentially analyzed so as to incrementaly construct the model. Each new image
      provides information which refines the model. We describe some experiments toward
      this end. Our method of extracting 3-D shape information from the images is
      stereo analysis. Because we are dealing with urban scenes, a junction-based
      matching technique proves very useful. This technique produces rather sparse wire
      frame descriptions of the scene. A reasoning system that relies on task-specific
      knowledge generates an approximate model of the scene from the stereo output.
      Gray scale information is also acquired for the faces in the model. Finally, we
      describe an experiment in combining two views of the scene to obtain a rermed
      model.

PMID- 21869201
TI  - Representation and shape matching of 3-d objects.
AB  - A three-dimensional scene analysis system for the shape matching of real world 3
      D objects is presented. Various issues related to representation and modeling of
      3-D objects are addressed. A new method for the approximation of 3-D objects by a
      set of planar faces is discussed. The major advantage of this method is that it
      is applicable to a complete object and not restricted to single range view which
      was the limitation of the previous work in 3-D scene analysis. The method is a
      sequential region growing algorithm. It is not applied to range images, but
      rather to a set of 3-D points. The 3-D model of an object is obtained by
      combining the object points from a sequence of range data images corresponding to
      various views of the object, applying the necessary transformations and then
      approximating the surface by polygons. A stochastic labeling technique is used to
      do the shape matching of 3-D objects. The technique matches the faces of an
      unknown view against the faces of the model. It explicitly maximizes a criterion
      function based on the ambiguity and inconsistency of classification. It is
      hierarchical and uses results obtained at low levels to speed up and improve the
      accuracy of results at higher levels. The objective here is to match the
      individual views of the object taken from any vantage point. Details of the
      algorithm are presented and the results are shown on several unknown views of a
      complicated automobile casting.

PMID- 21869202
TI  - A syntactic approach to 3-d object representation.
AB  - A 3-D object representation scheme which uses surfaces as primitives and
      grammatical production rules as structural relationship descriptors is proposed.
      Possible selections of surface primitives are discussed. Examples are given to
      illustrate the object description method.

PMID- 21869203
TI  - On encoding boundaries with quadtrees.
AB  - The ''line quadtree'' data structure hierarchically represents a region and its
      boundary. Based on the standard quadtree, each node in this structure stores
      adjacency information as well. While line quadtrees use the same amount of space
      as standard qaudtrees, they facilitate several region processing algorithms. In
      particular, we describe efficient algorithms for boundary and superimposing two
      maps encoded as line quadtrees.

PMID- 21869204
TI  - Adaptive relaxation labeling.
AB  - Current implementation of probabilistic relaxation labeling (PRL) is based on
      stationary compatibility coefficients (SCC's). Such labeling frequently diverges
      from an achieved minimum labeling error. In this correspondence it is shown that
      by having nonstationary compatibility coefficients (NSCC's) the PRL stabilizes
      about the minimum error which is obtained during the early iterations. Also, a
      noniterative labeling algorithm which uses NSCC and has a performance similar to
      that of the modified PRL is suggested.

PMID- 21869205
TI  - Digital disks.
AB  - Geometric properties of digital disks are discussed. An algorithm is presented
      that determines whether or not a given digital region is a digital disk.

PMID- 21869206
TI  - A two-stage cross correlation approach to template matching.
AB  - Two-stage template matching with sum of absolute differences as the similarity
      measure has been developed by Vanderburg and Rosenfeld [1], [2]. This
      correspondence shows the development of two-stage template matching with cross
      correlation as the similarity measure. The threshold value of the first-stage is
      derived analytically and its validity is verified experimentally. Considerable
      speed-up over the one-stage process can be obtained by introducing only a small
      false dismissal probability.

PMID- 21869207
TI  - Classification Bias of the k-Nearest Neighbor Algorithm.
AB  - The k-nearest neighbor classifier has been used extensively in pattern analysis
      applications. This classifier can, however, have substantial bias when there is
      little class separation and the sample sizes are unequal. This classification
      bias is examined for the two-class situation and formulas presented that allows
      selection of values of k that yields minimum bias.

PMID- 21869208
TI  - Research on machine recognition of handprinted characters.
AB  - Machine recognition of handprinted Chinese characters has recently become very
      active in Japan. Both from the practical and the academic point of view, very
      encouraging results are reported. The work is described systematically and
      analyzed in terms of so-called feature matching, which is likely to be the
      mainstream of the research and development of machine recognition of handprinted
      Chinese characters. A database, ETL8 (881 Kanji, 71 hirakana, and 160 variations
      for each category), is explained, on which many experiments were performed.
      Recognition rates reported using this database can be compared, and so somewhat
      qualitative evaluation of these methods is described. Based on the comparative
      study, the merits and demerits of both feature and structural matching are
      discussed and some future directions are mentioned.

PMID- 21869209
TI  - Analysis and design of a decision tree based on entropy reduction and its
      application to large character set recognition.
AB  - Based on a recursive process of reducing the entropy, the general decision tree
      classifier with overlap has been analyzed. Several theorems have been proposed
      and proved. When the number of pattern classes is very large, the theorems can
      reveal both the advantages of a tree classifier and the main difficulties in its
      implementation. Suppose H is Shannon's entropy measure of the given problem. The
      theoretical results indicate that the tree searching time can be minimized to the
      order O(H), but the error rate is also in the same order O(H) due to error
      accumulation. However, the memory requirement is in the order 0(H exp(H)) which
      poses serious problems in the implementation of a tree classifier for a large
      number of classes. To solve these problems, several theorems related to the
      bounds on the search time, error rate, memory requirement and overlap factor in
      the design of a decision tree have been proposed and some principles have been
      established to analyze the behaviors of the decision tree. When applied to
      classify sets of 64, 450, and 3200 Chinese characters, respectively, the
      experimental results support the theoretical predictions. For 3200 classes, a
      very high recognition rate of 99.88 percent was achieved at a high speed of 873
      samples/s when the experiment was conducted on a Cyber 172 computer using a high
      level language.

PMID- 21869210
TI  - Bayesian recognition of local 3-d shape by approximating image intensity
      functions with quadric polynomials.
AB  - The recognition in image data of viewed patches of spheres, cylinders, and planes
      in the 3-D world is discussed as a first step to complex object recognition or
      complex object location and orientation estimation. Accordingly, an image is
      partitioned into small square windows, each of which is a view of a piece of a
      sphere, or of a cylinder, or of a plane. Windows are processed in parallel for
      recognition of content. New concepts and techniques include approximations of the
      image within a window by 2-D quadric polynomials where each approximation is
      constrained by one of the hypotheses that the 3-D surface shape seen is either
      planar, cylindrical, or spherical; a recognizer based upon these approximations
      to determine whether the object patch viewed is a piece of a sphere, or a piece
      of a cylinder, or a piece of a plane; lowpass filtering of the image by the
      approximation. The shape recognition is computationally simple, and for large
      windows is approximately Bayesian minimum-probability-of-error recognition. These
      classifications are useful for many purposes. One such purpose is to enable a
      following processor to use an appropriate estimator to estimate shape, and
      orientation and location parameters for the 3-D surface seen within a window.

PMID- 21869211
TI  - 3-d space location and orientation parameter estimation of lambertian spheres and
      cylinders from a single 2-d image by fitting lines and ellipses to thresholded
      data.
AB  - An approach to object location and orientation estimation is discussed in which
      objects in 3-D space are approximated by chunks of spheres, cylinders, and
      planes. The surface-shape parameters of these chunks of primitive subobjects are
      estimated in real time from a single 2-D image assuming a Lambertian reflection
      model. This processing is realized by partitioning an image into small square
      windows and processing the windows in parallel. It is assumed that a small window
      views a portion of one of the spherical, cylindrical or planar chunks. The paper
      applies standard statistical estimators in new ways to the estimation of the 3-D
      shape parameters for spherical and cylindrical surfaces. Linear regression and
      scatter matrix eigenvalue analysis techniques are used here. The algorithms are
      computationally simple yet are robust and can handle noisy highly variable data.

PMID- 21869212
TI  - Two-dimensional critical point configuration graphs.
AB  - The configuration of the critical points of a smooth function of two variables is
      studied under the assumption that the function is Morse, that is, that all of its
      critical points are nondegenerate. A critical point configuration graph (CPCG) is
      derived from the critical points, ridge lines, and course lines of the function.
      Then a result from the theory of critical points of Morse functions is applied to
      obtain several constraints on the number and type of critical points that appear
      on cycles of a CPCG. These constraints yield a catalog of equivalent CPCG cycles
      containing four entries. The slope districts induced by a critical point
      configuration graph appear useful for describing the behavior of smooth functions
      of two variables, such as surfaces, images, and the radius function of three
      dimensional symmetric axes.

PMID- 21869213
TI  - Discrete representation of straight lines.
AB  - If a continuous straight line segment is digitized on a regular grid, obviously a
      loss of information occurs. As a result, the discrete representation obtained
      (e.g., a chaincode string) can be coded more conveniently than the continuous
      line segment, but measurements of properties (such as line length) performed on
      the representation have an intrinsic inaccuracy due to the digitization process.
      In this paper, two fundamental properties of the quantization of straight line
      segments are treated. 1) It is proved that every ''straight'' chaincode string
      can be represented by a set of four unique integer parameters. Definitions of
      these parameters are given. 2) A mathematical expression is derived for the set
      of all continuous line segments which could have generated a given chaincode
      string. The relation with the chord property is briefly discussed.

PMID- 21869214
TI  - Multiprocessor pyramid architectures for bottom-up image analysis.
AB  - This paper describes three hierarchical organizations of small processors for
      bottom-up image analysis:pyramids, interleaved pyramids, and pyramid trees.
      Progressively lower levels in the hierarchies process image windows of decreasing
      size. Bottom-up analysis is made feasible by transmitting up the levels quadrant
      borders and border-related information that captures quadrant interaction of
      interest for a given computation. The operation of the pyramid is illustrated by
      examples of standard algorithms for interior-based computations (e.g., area) and
      border-based computations of local properties (e.g., perimeter). A connected
      component counting algorithm is outlined that illustrates the role of border
      related information in representing quadrant interaction. Interleaved pyramids
      are obtained by sharing processors among several pyramids. They increase
      processor utilization and throughput rate at the cost of increased hardware.
      Trees of shallow interleaved pyramids, calld pyramid trees, are introduced to
      reduce the hardware requirements of large interleaved pyramids at the expense of
      increased processing time, without sacrificing processor utilization. The three
      organizations are compared with respect to several performance measures.

PMID- 21869215
TI  - Picture indexing and abstraction techniques for pictorial databases.
AB  - We present an approach for picture indexing and abstraction. Picture indexing
      facilitates information retrieval from a pictorial database consisting of picture
      objects and picture relations. To construct picture indexes, abstraction
      operations to perform picture object clustering and classification are
      formulated. To substantiate the abstraction operations, we also formalize
      syntactic abstraction rules and semantic abstraction rules. We then illustrate by
      examples how to apply these abstraction operations to obtain various picture
      indexes, and how to construct icons to facilitate accessing of pictorial data.

PMID- 21869216
TI  - Database Structure and Manipulation Capabilities of a Picture Database Management
      System (PICDMS).
AB  - The database structure and data manipulation capabilities of a generalized
      PICture Database Management System (PICDMS) are presented. They are based on a
      dynamic, stacked-image, logical database structure that uses gridded, rather than
      topological, data representation. A prototype PICDMS has been designed and
      implemented. A commercial version is being used as a generator of image
      processing programs. The system has novel capabilities for nonprogrammer users:
      it is able to 1) build multiple-variable databases from photographs and other two
      dimensional data sources such as maps, drawings, etc., and 2) manipulate such
      data using simple logical commands. Physical organization and accessing
      strategies are outlined. A summary of the PICDMS data manipulation capabilities
      is presented and a subset of operations is illustrated with brief examples. A
      comprehensive example displays PICDMS capabilities and the programming advantages
      it possesses over other approaches.

PMID- 21869217
TI  - Word-meaning selection in multiprocess language understanding programs.
AB  - An understander reading or listening to someone speak has to repeatedly solve the
      problem of word-meaning ambiguity, the selection of the intended meaning of a
      word from the set of its possible meanings. For example, the problem of
      pronominal reference can be considered as a choosing of the intended referent
      from the collection of entities which have already been mentioned or which can be
      inferred. Human understanders apply rules of syntax, surface semantics, general
      world knowledge, and various types of contextual knowledge to resolve word-sense
      or pronominal ambiguity as they process language. We describe a mechanism, called
      a cooperative word-meaning selector, which allows the computer to use various
      knowledge sources as it ''understands'' text. The word-meaning selector is part
      of a conceptual analyzer which forms the natural-language interface for a pair of
      multiprocess language processing systems. The first, called DSAM (distributable
      script applier mechanism), reads and summarizes newspaper articles making heavy
      reference to situational scripts. The second, ACE (academic counseling
      experiment), is a conversational program which automates certain parts of the
      academic counseling task. In each of these systems, a variety of knowledge
      sources, each managed by a distinct ''expert'' process, is brought to bear to
      enable the word-meaning selector to form the most plausible reading of a sentence
      containing ambiguous words.

PMID- 21869218
TI  - Solving satisfiability with less searching.
AB  - A new technique, complement searching, is given for reducing the amount of
      searching required to solve satisfiability (constraint satisfaction) problems.
      Search trees for these problems often contain subtrees that have approximately
      the same shape. When this occurs, knowledge that the first subtree does not have
      a solution can be used to reduce the searching in the second subtree. Only the
      part of the second subtree which is different from the first needs to be
      searched. The pure literal rule of the Davis-Putnam procedure is a special case
      of complement searching. The new technique greatly reduces the amount of
      searching required to solve conjunctive normal form predicates that contain
      almost pure literals (literals with a small number of occurrences).

PMID- 21869219
TI  - Matching three-dimensional objects using silhouettes.
AB  - A method for matching three-dimensional objects against a library of models from
      an observed sequence of silhouettes is presented in this correspondence. Based
      upon the observed silhouettes, the three-dimensional structure of the object is
      constructed and refined. The principal moments and three primary silhouettes are
      computed for the constructed three-dimensional objects to represent the aggregate
      and detailed structure parameters. The adaptive matching technique requires that
      sufficient silhouettes be added to modify the structure of the unknown object
      until consistent and steady matching results are obtained. The library for
      matching is based on three primary silhouettes of the model objects. Experiments
      conducted show a fast convergence to a consistent result may be achieved provided
      that a reasonable choice of silhouettes is made.

PMID- 21869220
TI  - Multiple resolution texture analysis and classification.
AB  - Textures are classified based on the change in their properties with changing
      resolution. The area of the gray level surface is measured at serveral
      resolutions. This area decreases at coarser resolutions since fine details that
      contribute to the area disappear. Fractal properties of the picture are computed
      from the rate of this decrease in area, and are used for texture comparison and
      classification. The relation of a texture picture to its negative, and
      directional properties, are also discussed.

PMID- 21869221
TI  - Determining motion parameters for scenes with translation and rotation.
AB  - A study of methods that determine the rotation parameters of a camera moving
      through synthetic and real scenes is conducted. Algorithms that combine ideas of
      Jain and Prazdny, using hypothesizeand-verify paradigm, are developed to find
      translational and rotational parameters. An argument is made for using
      hypothesized motion parameters rather than relaxation labeling to find
      correspondence. Some work with real scenes shows the difficulties introduced by
      noise, the lack of resolution, and the need for better low-level techniques.

PMID- 21869222
TI  - A posteriori estimation of correlated jointly gaussian mean vectors.
AB  - This paper describes the use of maximum a posteriori probability (MAP) techniques
      to estimate the mean values of features used in statistical pattern
      classification problems, when these mean feature values from the various decision
      classes are jointly Gaussian random vectors that are correlated across the
      decision classes. A set of mathematical formalisms is proposed and used to derive
      closed-form expressions for the estimates of the class-conditional mean vectors,
      and for the covariance matrix of the errors of these estimates. Finally, the
      performance of these algorithms is described for the simple case of a two-class
      one-feature pattern recognition problem, and compared to the performance of
      classical estimators that do not exploit the class-to-class correlations of the
      features' mean values.

PMID- 21869223
TI  - Estimation of error rates in classification of distorted imagery.
AB  - This correspondence considers the problem of matching image data to a large
      library of objects when the image is distorted. Two types of distortions are
      considered: blur-type, in which a transfer function is applied to Fourier
      components of the image, and scale-type, in which each Fourier component is
      mapped into another. The objects of the library are assumed to be normally
      distributed in an appropriate feature space. Approximate expressions are
      developed for classification error rates as a function of noise. The error rates
      they predict are compared with those from classification of artificial data,
      generated by a Gaussian random number generator, and with error rates from
      classification of actual data. It is demonstrated that, for classification
      purposes, distortions can be characterized by a small number of parameters.

PMID- 21869224
TI  - Some experiments on estimating the 3-d motion parameters of a rigid body from two
      consecutive image frames.
AB  - This paper describes the results of some experiments on estimating the 3-D motion
      parameters of a rigid body from two consecutive TV images, and discusses several
      factors which affect the accuracy of the results. These factors include the sizes
      of the motion parameters themselves, the accuracy of the raw data, and the number
      of point correspondences. In addition, we address two related topics: determining
      corner positions to subpixel accuracy and matching point patterns with different
      scales.

PMID- 21869225
TI  - Low level image segmentation: an expert system.
AB  - A major problem in robotic vision is the segmentation of images of natural scenes
      in order to understand their content. This paper presents a new solution to the
      image segmentation problem that is based on the design of a rule-based expert
      system. General knowledge about low level properties of processes employ the
      rules to segment the image into uniform regions and connected lines. In addition
      to the knowledge rules, a set of control rules are also employed. These include
      metarules that embody inferences about the order in which the knowledge rules are
      matched. They also incorporate focus of attention rules that determine the path
      of processing within the image. Furthermore, an additional set of higher level
      rules dynamically alters the processing strategy. This paper discusses the
      structure and content of the knowledge and control rules for image segmentation.

PMID- 21869226
TI  - A necessary and sufficient condition for a picture to represent a polyhedral
      scene.
AB  - As Shapira pointed out, a theorem by the author on line drawings of polyhedral
      scenes was not accurate. The present paper shows that the validity of the theorem
      is attained by a slight revision of the formulation.

PMID- 21869227
TI  - Modeling of atmospheric disturbances in meteorological pictures.
AB  - This paper describes a model-based approach to perform tracking of extratropical
      atmospheric disturbances from a sequence of satellite cloud-cover images. More
      precisely, it deals with the estimation of motion of these spiral-shaped cloud
      systems (both translational and rotational motion), and the measurement of the
      evolution of their shape. Tracking is achieved by recording from one image to the
      next the changes of the model parameter values. A maximum likelihood criterion is
      used in the process of fitting model to sensed data. The defined model takes into
      account geometric and intensity aspects. Such an approach readily yields global
      information on the disturbance cloud system of interest. As a requirement in such
      an application is robustness to noise, to this end two versions of the modeling
      have been considered.

PMID- 21869228
TI  - Toward a fundamental theory of optimal feature selection: part I.
AB  - Several authors have studied the problem of dimensionality reduction or feature
      selection using statistical distance measures, e.g., the Chernoff coefficient,
      Bhattacharyya distance, I-divergence, and J-divergence because they generally
      felt that direct use of the probability of classification error expression was
      either computationally or mathematically intractable. We show that for the
      difficult problem of testing one weakly stationary Gaussian stochastic process
      against another when the mean vectors are similar and the covariance matrices
      (patterns) differ, the probability of error expression may be dealt with directly
      using a combination of classical methods and distribution function theory. The
      results offer a new and accurate finite dimensionality information-theoretic
      strategy to feature selection, and are shown, by use of examples, to be superior
      to the well-known Kadota-Shepp approach which employs distance measures and
      asymptotics in its formulation. The present Part I deals with the theory; Part II
      deals with the implementation of a computer-based real-time pattern classifier
      which takes into account a realistic quasi-stationarity of the patterns.

PMID- 21869229
TI  - A walsh-hadamard based distributed storage device for the associative search of
      information.
AB  - A computer model for a distributed associative memory has been developed based on
      Walsh-Hadamard functions. In this memory device, the information storage is
      distributed over the entire memory medium and thereby lends itself to parallel
      comparison of the input with stored data. These inherent economic storage and
      parallel processing capabilities may be found effective especially in real-time
      processing of large amount of information. However, overlaying different pieces
      of data in the same memory medium creates the problem of interference or
      crosstalk between stored data and may lead to recognition errors. In this paper,
      a crosstalk reduction technique utilizing the gradient descent procedure is
      developed first. This minimizes the memory processing error and enhances memory
      saving. Second, for an efficient implementation of the memory structure, these
      associative memories are configured in a hierarchical structure which not only
      expands storage capacity but also utilizes the speed of tree search. Finally, a
      self-correcting technique is developed which achieves error-free recognition of
      near neighbors for any training pattern even among the presence of crosstalk.

PMID- 21869230
TI  - Segmentation of frame sequences obtained by a moving observer.
AB  - In many applications of computer vision, a frame sequence may be acquired using a
      moving camera. We propose ego-motion polar transformation for segmentation of
      such sequences. It is shown that segmentation and extraction of motion
      information become easier in the transformed domain. Our experience with a
      translating camera indicates that this technique can play a very important role
      in the analysis of moving observer dynamic scenes.

PMID- 21869231
TI  - On the detection of peaks and valleys using the local descriptors method.
AB  - In this correspondence it is demonstrated that the derivative of the angle with
      respect to an arbitrary independent parameter cannot in general be used to find
      peaks and valleys of a shape. It is then shown, using concepts from differential
      geometry, that curvature corresponds to the derivative of the angle with respect
      to an independent variable if and only if the angle is deflned as a single
      variable. It is further shown that peaks and valleys detected using curvature as
      a criterion are insufficient to completely describe a shape.

PMID- 21869232
TI  - Spirograph theory: a framework for calculations on digitized straight lines.
AB  - Using diagrams called ''spirographs'' a general theory is developed with which
      one can easily perform calculations on various aspects of digitized straight
      lines. The mathematics of the theory establishes a link between digitized
      straight lines and the theory of numbers (Farey series, continued fractions). To
      show that spirograph theory is a useful unification, we derive two previously
      known advanced results within the framework of the theory, and new results
      concerning the accuracy in position of a digitized straight line as a function of
      its slope and length.

PMID- 21869233
TI  - Three-dimensional digital planes.
AB  - Definitions of 3-D digital surface and plane are introduced. Many geometric
      properties of these objects are examined. In particular, it is shown that digital
      convexity is neither a necessary nor a sufficient condition for a digital surface
      element to be a convex digital plane element, but it is both necessary and
      sufficient for a digital surface to be a digital plane. Also algorithms are
      presented to determine whether or not a finite set of digital points is a
      (convex) digital plane element.

PMID- 21869234
TI  - Cluster definition by the optimization of simple measures.
AB  - We adopt the following measures of clustering based on simple edge counts in an
      undirected loop-free graph. Let S be a subset of the points of the graph. The
      compactness of S is measured by the number of edges connecting points in S to
      other points in S. The isolation or separation of S is measured by the negative
      of the number of edges connecting points in S to points not in S. The subset S is
      a cluster if it is compact and isolated. We study the cluster search problem:
      find a subset S which maximizes a linear combination of the compactness and
      (negative) isolation edge counts. We show that a closely related decision problem
      is NP-complete. We develop a pruned search tree algorithm which is much faster
      than complete search, especially for graphs which are derived from points
      embedded in a space of low dimensionality.

PMID- 21869235
TI  - Properties of separable covariance matrices and their associated gaussian random
      processes.
AB  - A number of properties of separable covariance matrices are summarized.
      Expressions for the divergence of the corresponding two-dimensional Gaussian
      random processes are given in terms of row and column covariance matrices, and in
      terms of linear prediction parameters and maximum likelihood spectral estimates.
      Such time and frequency domain expressions are not widely known, even for one
      dimensional random processes.

PMID- 21869236
TI  - More about polyhedra-interpretation through constructions in the image plane.
AB  - This paper deals with the interpretation and feasibility check of line drawings
      representing polyhedral scenes. The polyhedra are of general types and there are
      no restrictions on camera position. The geometric consistency check and the line
      labeling are carried out through constructions in the image plane. An algorithm
      for the geometric construction is suggested, and the necessary conditions for
      these constructions are discussed. The image plane construction can be used for
      preparing labeled junction catalogs for junctions other than trihedral. In
      addition the paper analyzes the relation between the image plane construction and
      the gradient space construction suggested by Mackworth [7] for the same purpose.

PMID- 21869237
TI  - Computational experiments with a feature based stereo algorithm.
AB  - Computational models of the human stereo system can provide insight into general
      information processing constraints that apply to any stereo system, either
      artificial or biological. In 1977 Marr and Poggio proposed one such computational
      model, which was characterized as matching certain feature points in difference
      of-Gaussian filtered images and using the information obtained by matching
      coarser resolution representations to restrict the search space for matching
      finer resolution representations. An implementation of the algorithm and its
      testing on a range of images was reported in 1980. Since then a number of
      psychophysical experiments have suggested possible refinements to the model and
      modifications to the algorithm. As well, recent computational experiments
      applying the algorithm to a variety of natural images, especially aerial
      photographs, have led to a number of modifications. In this paper, we present a
      version of the Marr-Poggio-Grimson algorithm that embodies these modifications,
      and we illustrate its performance on a series of natural images.

PMID- 21869238
TI  - A three-dimensional vision by off-shelf system with multi-cameras.
AB  - A three-dimnensional vision system for on-line operation that aids a collision
      avoidance system for an industrial robot is developed. Because of the real-time
      requirement, the process that locates and describes the obstacles must be fast.
      To satisfy the safety requirement, the obstacle model should always contain the
      physical obstacle entirely. This condition leads to the bounding box description
      of the obstacle, which is simple for the computer to process. The image
      processing is performed by a Machine Intelligence Corporation VS-100 machine
      vision system. The control and object perception is performed by the developed
      software on a host Digital Equipment Corporation VAX 11/780 Computer. The
      resultant system outputs a file of the locations and bounding descriptions for
      each object found. When the system is properly calibrated, the bounding
      descriptions always completely envelop the obstacle. The response time is data
      dependent. When using two cameras and processed on UNIX time sharing mode, the
      average response time will be less than 2 s if eight or fewer objects are
      present. When using all three cameras, the average response time will be less
      than 4 s if eight or fewer objects are present.

PMID- 21869239
TI  - Image normalization by complex moments.
AB  - The role of moments in image normalization and invariant pattern recognition is
      addressed. The classical idea of the principal axes is analyzed and extended to a
      more general definition. The relationship between moment-based normalization,
      moment invariants, and circular harmonics is established. Invariance properties
      of moments, as opposed to their recognition properties, are identified using a
      new class of normalization procedures. The application of moment-based
      normalization in pattern recognition is demonstrated by experiment.

PMID- 21869240
TI  - Parallel algorithms for syllable recognition in continuous speech.
AB  - A distributed rule-based system for automatic speech recognition is described.
      Acoustic property extraction and feature hypothesization are performed by the
      application of sequences of operators. These sequences, called plans, are
      executed by cooperative expert programs. Experimental results on the automatic
      segmentation and recognition of phrases, made of connected letters and digits,
      are described and discussed.

PMID- 21869241
TI  - An evaluation based theorem prover.
AB  - A noninductive method for mechanical theorem proving is presented, which deals
      with a recursive class of theorems involving iterative functions and predicates.
      The method is based on the symbolic evaluation of the formula to be proved and
      requires no inductive step. Induction is avoided since a metatheorem is proved
      which establishes the conditions on the evaluation of any formula which are
      sufficient to assure that the formula actually holds. The proof of a supposed
      theorem consists in evaluating the formula and checking the conditions. The
      method applies to assertions that involve element-by-element checking of typed
      homogeneous sequences which are hierarchically constructed out of the primitive
      type consisting of the truth values. The sequences can be computed by means of
      iterative and ''accumulator'' functions. The paper includes the definition of a
      simple typed iterative language in which both predicates and functions are
      expressed. The language precisely defines the scope of the proof method. The
      method proves a wide variety of theorems about iterative functions on sequences,
      including that which states that REVERSE is its own inverse, and that it can be
      inversely distributed on APPEND, that FLATTEN can be distributed on APPEND and
      that each element of any sequence is a MEMBER of the sequence itself. Although
      the method is not complete, it does provide the basis for an extremely efficient
      tool to be used in a complete mechanical theorem prover.

PMID- 21869242
TI  - A VLSI Systolic Architecture for Pattern Clustering.
AB  - Cluster analysis is a valuable tool in exploratory pattern analysis, especially
      when very little prior information about the data is available. In unsupervised
      pattern recognition and image segmentation applications, clustering techniques
      play an important role. The squared-error clustering technique is the most
      popular one among different clustering techniques. Due to the iterative nature of
      the squared-error clustering, it demands substantial CPU time, even for modest
      numbers of patterns. Recent advances in VLSI microelectronic technology triggered
      the idea of implementing the squared-error clustering directly in hardware. A two
      level pipelined systolic pattern clustering array is proposed in this paper. The
      memory storage and access schemes are designed to enable a rhythmic data flow
      between processing units. Each processing unit is pipelined to further enhance
      the system performance. The total processing time for each pass of pattern
      labeling and cluster center updating is essentially dominated by the time
      required to fetch the pattern matrix once. Detailed architectural configuration,
      system performance evaluation, and simulation experiments are presented. The
      modularity and the regularity of the system architecture make it suited for VLSI
      implementations.

PMID- 21869243
TI  - A metric for comparing relational descriptions.
AB  - Relational models are frequently used in high-level computer vision. Finding a
      correspondence between a relational model and an image description is an
      important operation in the analysis of scenes. In this paper the process of
      finding the correspondence is formalized by defining a general relational
      distance measure that computes a numeric distance between any two relational
      descriptions-a model and an image description, two models, or two image
      descriptions. The distance measure is proved to be a metric, and is illustrated
      with examples of distance between object models. A variant measure used in our
      past studies is shown not to be a metric.

PMID- 21869244
TI  - A top-down quadtree traversal algorithm.
AB  - Many standard image processing operations can be implemented using quadtrees as a
      simple tree traversal where, at each terminal node, a computation is performed
      involving some of that node's neighbors. Most of this work has involved the use
      of bottom-up neighbor-finding techniques which search for a nearest common
      ancestor. Recently, top-down techniques have been proposed which make use of a
      neighbor vector as the tree is traversed. A simplified version of the top-down
      method for a quadtree in the context of a general-purpose tree traversal
      algorithm is presented. It differs, in part, from prior work in its ability to
      compute diagonally adjacent neighbors rather than just horizontally and
      vertically adjacent neighbors. It builds a neighbor vector for each node using a
      minimal amount of information. Analysis of the algorithm shows that its execution
      time is directly proportional to the number of nodes in the tree. However, it
      does require some extra storage. Use of the algorithm leads to lower execution
      time bounds for some common quadtree image processing operations such as
      connected component labeling.

PMID- 21869245
TI  - Fourier encoding of closed planar boundaries.
AB  - A circular Gaussian autoregressive (CGAR) source is used as a model for closed
      planar curves. A class of suboptimal encoding schemes is considered which
      separately quantize the Fourier coefficients of the boundary. Application of rate
      distortion theoretic techniques leads to parametric equations describing the
      optimal encoding bound. Interpretation of these equations establishes a sampling
      criterion and a computationally efficient transform encoding scheme for the
      suboptimal class. Several variants of this transform encoding scheme are
      suggested and compared to the encoding bound.

PMID- 21869246
TI  - A New Heuristic Search Technique-Algorithm SA.
AB  - In this paper, we present a new heuristic searching algorithm by introducing the
      statistical inference method on the basis of algorithm A (or A*). It is called
      algorithm SA. In a simplified search space, a uniform m-ary tree, we obtain the
      following result. Using algorithm SA, a goal node can be found with probability
      one, and its mean complexity is O(N.ln N) where N is the depth at which the goal
      is located.

PMID- 21869247
TI  - The 2-NN Rule for More Accurate NN Risk Estimation.
AB  - By proper design of a nearest-neighbor (NN) rule, it is possible to reduce
      effects of sample size in NN risk estimation. The 2-NN rule for the two-class
      problem eliminates the first-order effects of sample size. Since its asymptotic
      value is exactly half that of the 1-NN rule, it is possible to substitute the 2
      NN rule for the 1-NN rule with a resultant increase in accuracy. For further
      stabilization of the risk estimate with respect to sample size, 2-NN polarization
      is suggested. Examples are included. The 2-NN approach is extended to M-class and
      2k-NN.

PMID- 21869248
TI  - The separating capacity of a multithreshold threshold element.
AB  - In answer to what represents the intrinsic information-processing capability of
      the pattern classification system, Cover [1] has defined the separating capacity,
      and has derived it for the linear machine and the so-called ? machine. In this
      paper, the separating capacity of a multithreshold classification element is
      obtained. It is shown that the capacity of a multithreshold threshold element
      with k thresholds-k-threshold element-in n-dimensional space is 2(n + k). A
      linear machine is a special case in the k-threshold element with k = 1;
      therefore, its capacity becomes 2(n + 1) from the above result. Further, although
      it is intuitively apparent that the larger the number of thresholds, the more
      powerful the information-processing capability of the k-threshold element, using
      the capacity as a measure of this capability, we may now state that the
      separating power of the k-threshold element increases linearly with respect to k.

PMID- 21869249
TI  - Handling memory overflow in connected component labeling applications.
AB  - The storage requirements for component labeling and feature extraction operations
      are unknown a priori. Whenever large images are processed, many labels, and thus
      a large amount of storage, may be required, making hardware implementation
      difficult. The proposed labeling procedure eliminates memory overflow by enabling
      the reuse of memory locations in which features of nonactive labels had been
      stored. The storage requirement for the worst case conditions is analyzed and is
      shown to be realizable. The basic procedure can be implemented in two modes, an
      interrupted mode or a parallel mode. A hardware design is presented.

PMID- 21869250
TI  - Comments on ''digital step edges from zero crossings of second directional
      derivatives''.
AB  - In a recent paper,1 Haralick published an edge detection scheme that was
      supported, in part, by an evaluation against the Prewitt and the Marr-Hildreth
      (?2G) operators. This evaluation led to the conclusion that Haralick's method
      performed the best, and the ?2G operator performed the worst. The implementation
      of the ?2G operator, on which this evaluation was based, differed significantly
      from that used by Marr and Hildreth. Evaluation of the performance of the Marr
      Hildreth implementation of the ?2G operator on similar images shows that this
      edge detection method in fact performs comparably to the Prewitt and Haralick
      operators.

PMID- 21869251
TI  - Author's Reply.
AB  - We present evidence that the Laplacian zero-crossing operator does not use
      neighborhood information as effectively as the second directional derivative edge
      operator. We show that the use of a Gaussian smoother with standard deviation 5.0
      for the Laplacian of a Gaussian edge operator with a neighborhood size of 50 * 50
      both misses and misplaces edges on an aerial image of a mobile home park.
      Contrary to Grimson and Hildreth's results, our results of the Laplacian edge
      detector on a noisy test checkerboard image are also not as good as the second
      directional derivative edge operator. We conclude by discussing a number of open
      issues on edge operator evaluation.

PMID- 21869252
TI  - Analysis of accretion and deletion at boundaries in dynamic scenes.
AB  - In dynamic scenes, the presence of object boundaries is often signaled by the
      appearance or disappearance of occluded surfaces over time. Such regions of
      surface accretion or deletion can be found using matching techniques similar to
      those used to determine optical flow in an image sequence. Regions in one frame
      that are not adequately matched by any region in previous frames correspond to
      accretion. Regions that have no matches in subsequent frames correspond to
      deletion. In either case, an occlusion boundary is present. Furthermore, by
      associating accretion or deletion regions with a surface on one side of a
      boundary, it is possible to determine which side of the boundary is being
      occluded. This association can be based purely on visual motion-the accretion or
      deletion region moves with the same image velocity as the remaining visible
      surface to which it is attached.

PMID- 21869253
TI  - Stereo by intra- and inter-scanline search using dynamic programming.
AB  - This paper presents a stereo matching algorithm using the dynamic programming
      technique. The stereo matching problem, that is, obtaining a correspondence
      between right and left images, can be cast as a search problem. When a pair of
      stereo images is rectified, pairs of corresponding points can be searched for
      within the same scanlines. We call this search intra-scanline search. This intra
      scanline search can be treated as the problem of finding a matching path on a two
      dimensional (2D) search plane whose axes are the right and left scanlines.
      Vertically connected edges in the images provide consistency constraints across
      the 2D search planes. Inter-scanline search in a three-dimensional (3D) search
      space, which is a stack of the 2D search planes, is needed to utilize this
      constraint. Our stereo matching algorithm uses edge-delimited intervals as
      elements to be matched, and employs the above mentioned two searches: one is
      inter-scanline search for possible correspondences of connected edges in right
      and left images and the other is intra-scanline search for correspondences of
      edge-delimited intervals on each scanline pair. Dynamic programming is used for
      both searches which proceed simultaneously: the former supplies the consistency
      constraint to the latter while the latter supplies the matching score to the
      former. An interval-based similarity metric is used to compute the score. The
      algorithm has been tested with different types of images including urban aerial
      images, synthesized images, and block scenes, and its computational requirement
      has been discussed.

PMID- 21869254
TI  - Dynamic measurement of computer generated image segmentations.
AB  - This paper introduces a general purpose performance measurement scheme for image
      segmentation algorithms. Performance parameters that function in real-time
      distinguish this method from previous approaches that depended on an a priori
      knowledge of the correct segmentation. A low level, context independent
      definition of segmentation is used to obtain a set of optimization criteria for
      evaluating performance. Uniformity within each region and contrast between
      adjacent regions serve as parameters for region analysis. Contrast across lines
      and connectivity between them represent measures for line analysis. Texture is
      depicted by the introduction of focus of attention areas as groups of regions and
      lines. The performance parameters are then measured separately for each area. The
      usefulness of this approach lies in the ability to adjust the strategy of a
      system according to the varying characteristics of different areas. This feedback
      path provides the means for more efficient and error-free processing. Results
      from areas with dissimilar properties show a diversity in the measurements that
      is utilized for dynamic strategy setting.

PMID- 21869255
TI  - Adaptive noise smoothing filter for images with signal-dependent noise.
AB  - In this paper, we consider the restoration of images with signal-dependent noise.
      The filter is noise smoothing and adapts to local changes in image statistics
      based on a nonstationary mean, nonstationary variance (NMNV) image model. For
      images degraded by a class of uncorrelated, signal-dependent noise without blur,
      the adaptive noise smoothing filter becomes a point processor and is similar to
      Lee's local statistics algorithm [16]. The filter is able to adapt itself to the
      nonstationary local image statistics in the presence of different types of signal
      dependent noise. For multiplicative noise, the adaptive noise smoothing filter is
      a systematic derivation of Lee's algorithm with some extensions that allow
      different estimators for the local image variance. The advantage of the
      derivation is its easy extension to deal with various types of signal-dependent
      noise. Film-grain and Poisson signal-dependent restoration problems are also
      considered as examples. All the nonstationary image statistical parameters needed
      for the filter can be estimated from the noisy image and no a priori information
      about the original image is required.

PMID- 21869256
TI  - Transformation between continuous and discrete representations of images: a
      perceptual approach.
AB  - The transformation of image signals between the continuous domain of the real
      world and the discrete domain of modern data processing can have a significant
      effect on quality and efficiency. Analysis based on perceptual rather than
      mathematical considerations has been carried out. A series of experiments based
      on the analysis has shown that substantial improvement over usual techniques can
      be achieved by the use of a cascade of a presharpening filter combined with
      Gaussian presampling and interpolation filters. The resulting ''sharpened
      Gaussian'' filter, although not exactly circularly symmetrical, gives a high
      degree of isotropy. Each element in the cascade is separable, so that
      computational efficiency is high. A favorable tradeoff is achieved among
      sharpness, smoothness, and the effects of aliasing. Subjective testing, in
      comparison with other commonly used filters, has shown the clear superiority of
      this filter.

PMID- 21869257
TI  - On the straightness of digital arcs.
AB  - The straightness of a digital arc can simply be determined by the absence of
      unevenness in its chain code. The absence of unevenness is a necessary and
      sufficient condition for a digital arc to have the chord property, and it offers
      a much simpler alternative for examining whether a digital arc has the chord
      property or not. This condition is also the most comprehensive and precise
      expression of the third criterion about digital straight lines given by Freeman.
      The relations among the chord property, Freeman's three criteria, and the
      hierarchical structure that a digital straight line supposedly have become much
      more clear. A procedure to detect the uneven segments and algorithms for
      determining the straightness of digital arcs is also included.

PMID- 21869258
TI  - Geometric algorithms for digitized pictures on a mesh-connected computer.
AB  - Although mesh-connected computers are used almost exclusively for low-level local
      image processing, they are also suitable for higher level image processing tasks.
      We illustrate this by presenting new optimal (in the O-notational sense)
      algorithms for computing several geometric properties of figures. For example,
      given a black/white picture stored one pixel per processing element in an n * n
      mesh-connected computer, we give ?(n) time algorithms for determining the extreme
      points of the convex hull of each component, for deciding if the convex hull of
      each component contains pixels that are not members of the component, for
      deciding if two sets of processors are linearly separable, for deciding if each
      component is convex, for determining the distance to the nearest neighboring
      component of each component, for determining internal distances in each
      component, for counting and marking minimal internal paths in each component, for
      computing the external diameter of each component, for solving the largest empty
      circle problem, for determining internal diameters of components without holes,
      and for solving the all-points farthest point problem. Previous mesh-connected
      computer algorithms for these problems were either nonexistent or had worst case
      times of ?(n2). Since any serial computer has a best case time of ?(n2) when
      processing an n * n image, our algorithms show that the mesh-connected computer
      provides significantly better solutions to these problems.

PMID- 21869259
TI  - Computing geometric properties of images represented by linear quadtrees.
AB  - The region quadtree is a hierarchical data structure that finds use in
      applications such as image processing, computer graphics, pattern recognition,
      robotics, and cartography. In order to save space, a number of pointerless
      quadtree representations (termed linear quadtrees) have been proposed. One
      representation maintains the nodes in a list ordered according to a preorder
      traversal of the quadtree. Using such an image representation and a graph
      definition of a quadtree, a general algorithm to compute geometric image
      properties such as the perimeter, the Euler number, and the connected components
      of an image is developed and analyzed. The algorithm differs from the
      conventional approaches to images represented by quadtrees in that it does not
      make use of neighbor finding methods that require the location of a nearest
      common ancestor. Instead, it makes use of a staircase-like data structure to
      represent the blocks that have been already processed. The worst-case execution
      time of the algorithm, when used to compute the perimeter, is proportional to the
      number of leaf nodes in the quadtree, which is optimal. For an image of size 2n *
      2n, the perimeter algorithm requires only four arrays of 2n positions each for
      working storage. This makes it well suited to processing linear quadtrees
      residing in secondary storage. Implementation experience has confirmed its
      superiority to existing approaches to computing geometric properties for images
      represented by quadtrees.

PMID- 21869260
TI  - On the comparison of conceptual clustering and numerical taxonomy.
AB  - Conceptual clustering requires that clusters formed in the process shall be
      definable in terms of simple formulas in the predicate calculus. Michalski and
      Stepp [1] have argued that the results obtained with this method are clearly
      superior to traditional methods of numerical classification, so that an order of
      magnitude degradation in performance is acceptable. In this paper the results and
      comparisons presented by Michalski and Stepp are reviewed and shown to be less
      than adequate to support such a conclusion. There are considerable problems with
      data coding and standardization, as well as choice of similarity measure, that
      make the results difficult to evaluate. Even accepting the clusters, two
      different valorizing schemes are used to evaluate the results obtained. In
      addition, the traditional agglomerative algorithm employed in numerical
      classification procedures can be adapted to perform conceptual clustering without
      an enormous degradation in performance. However, the value of the method can only
      be regarded as unproven.

PMID- 21869261
TI  - A knowledge based system for analysis of gated blood pool studies.
AB  - A system for obtaining a complete diagnostic description of an image sequence
      taken in nuclear medicine from the human heart has been developed, implemented,
      and tested. The knowledge about these images is represented in a semantic net,
      conclusions are drawn by a production rule approach, and scoring of alternative
      diagnoses is based on fuzzy membership functions. On the low level, image pixels
      are smoothed and organ contours are extracted; these are the input for the high
      level processing. Tests with several image sequences gave correct descriptions as
      compared to the diagnosis of a physician.

PMID- 21869262
TI  - A computational approach to approximate and plausible reasoning with applications
      to expert systems.
AB  - The intended purpose of this paper is twofold: proposing a common basis for the
      modeling of uncertainty and imprecision, and discussing various kinds of
      approximate and plausible reasoning schemes in this framework. Together with
      probability, different kinds of uncertainty measures (credibility and
      plausibility functions in the sense of Shafer, possibility measures in the sense
      of Zadeh and the dual measures of necessity, Sugeno's g?-fuzzy measures) are
      introduced in a unified way. The modeling of imprecision in terms of possibility
      distribution is then presented, and related questions such as the measure of the
      uncertainty of fuzzy events, the probability and possibility qualification of
      statements, the concept of a degree of truth, and the truth qualification of
      propositions, are discussed at length. Deductive inference from premises weighted
      by different kinds of measures by uncertainty, or by truth-values in the
      framework of various multivalued logics, is fully investigated. Then, deductive
      inferences from imprecise or fuzzy premises are dealt with; patterns of reasoning
      where both uncertainty and imprecision are present are also addressed. The last
      section is devoted to the combination of uncertain or imprecise pieces of
      information given by different sources. On the whole, this paper is a tentative
      survey of quantitative approaches in the modeling of uncertainty and imprecision
      including recent theoretical proposals as well as more empirical techniques such
      as the ones developed in expert systems such as MYCIN or PROSPECTOR, the
      management of uncertainty and imprecision in reasoning patterns being a key issue
      in artificial intelligence.

PMID- 21869263
TI  - Hierarchical coding of binary images.
AB  - Quadtrees are a compact hierarchical method of representation of images. In this
      paper, we explore a number of hierarchical image representations as applied to
      binary images, of which quadtrees are a single exemplar. We discuss quadtrees,
      binary trees, and an adaptive hierarchical method. Extending these methods into
      the third dimension of time results in several other methods. All of these
      methods are discussed in terms of time complexity, worst case and average
      compression of random images, and compression results on binary images derived
      from natural scenes. The results indicate that quadtrees are the most effective
      for two-dimensional images, but the adaptive algorithms are more effective for
      dynamic image sequences.

PMID- 21869264
TI  - Waveform correlation by tree matching.
AB  - A waveform correlation scheme is presented. The scheme consists of four parts: 1)
      the representation of waveforms by trees, 2) the definition of basic operations
      on tree nodes and tree distance, 3) a tree matching algorithm, and 4) a
      backtracking procedure to find the best node-to-node correlation. This
      correlation scheme has been implemented. Results show that the scheme has the
      capability of handling distortions that result from stretching or shrinking of
      intervals or from missing intervals.

PMID- 21869265
TI  - Space-Time Domain Expansion Approach to VLSI and Its Application to Hierarchical
      Scene Matching.
AB  - VLSI technology has recently received increasing attention due to its high
      performance and high reliability. Designing a VLSI structure systematically for a
      given task becomes a very important problem to many computer engineers. In this
      paper, we present a method to transform a recursive computation task into a VLSI
      structure systematically. The main advantages of this approach are its simplicity
      and completeness. Several examples, such as vector inner product, matrix
      multiplication, convolution, comparison operations in relational database and
      fast Fourier transformation (FFT), are given to demonstrate the transformation
      procedure. Finally, we apply the proposed method to hierarchical scene matching.
      Scene matching refers to the process of locating or matching a region of an image
      with a corresponding region of another view of the same image taken from a
      different viewing angle or at a different time. We first present a constant
      threshold estimation for hierarchical scene matching. The VLSI implementation of
      the hierarchical scene matching is then described in detail.

PMID- 21869266
TI  - The recovery of three-dimensional structure from image curves.
AB  - A class of inferences is described which allows the recovery of three-dimensional
      structures from the two-dimensional curves in an image. Unlike most previous
      methods, these inferences do not require restrictive assumptions or prior
      knowledge regarding the scene. They are based on the assumption that the camera
      viewpoint and the positions of the illumination sources are independent of the
      objects in the scene. From these independence assumptions, it can be shown that
      many potential interpretations of image curves are highly improbable. By
      eliminating these improbable interpretations it is possible to segment the image
      into sets of related image features and derive many three-space relations.

PMID- 21869267
TI  - The wedge filter technique for convex boundary estimation.
AB  - This paper describes a method for segmentation of convex shaped image regions.
      The wedge filter technique first employs the converging squares algorithm [1] to
      locate a region of interest. Then a region oriented boundary estimation
      technique, called the wedge filter, is applied. This wedge filter entails angular
      filtering and subsampling, and boundary interpolation. The technique is more
      capable of segmenting noncircular shapes than some earlier methods based on the
      Hough transform. In addition, unlike many edge-based segmentation schemes, this
      method is relatively tolerant to edge gaps and to blurred or thick edges. This
      technique is tested on a number of synthesized images over a range of convex
      shapes, for different algorithm parameters, and under various conditions of
      region size and image noise. In addition, the technique has been applied to
      segmentation of liver cell nuclei in light microscope images of human liver
      tissue.

PMID- 21869268
TI  - Contour map registration using fourier descriptors of gradient codes.
AB  - To estimate the position of a subpicture P1 (with unknown angular misaligment) in
      a contour map P2, a method based on Fourier descriptors of multidirectional
      gradient codes is suggested. It is assumed that P2 is characterized by a set of
      magnitudes at equally spaceddiscrete points over a rectangular area; and P1 is
      described by a set of magnitudes at discrete points on directional axes emanated
      from a point with magnitude c*. Using the measurements of P1, the
      multidirectional gradient or successive-gradient codes and their Fourier
      descriptors are generated. A contour map for P2 having c* as one of the isopleth
      values is then obtained. For each point on all c*-isopleths, a two-level
      classifier, utilizing information derived from the Fourier descriptors and the
      phase correlation function, is used to estimate the possible location of P1 in
      P2. Simulation has indicated that in many cases the angular misalignment and the
      position of P1 with respect to P2 can be determined.

PMID- 21869269
TI  - Template matching in rotated images.
AB  - A rotationally invariant template matching using normalized invariant moments is
      described. It is shown that if normalized invariant moments in circular windows
      are used, then template matching in rotated images becomes similar to template
      matching in translated images. A speedup technique based on the idea of two-stage
      template matching is also described. In this technique, the zeroth-order moment
      is used in the first stage to determine the likely match positions, and the
      second and third-order moments are used in the second stage to determine the best
      match position among the likely ones.

PMID- 21869270
TI  - Linear quadtrees from vector representations of polygons.
AB  - A new algorithm is presented which produces various forms of linear quadtrees
      directly from a vector representation of a polygon. This algorithm takes
      advantage of specific properties of linear quadtrees and associated linear keys
      to infer the colors of all parts of the region not cut by the polygon boundary.
      The method is further extended to multicolored (rather than binary) linear
      quadtrees which may be useful in geographic information systems applications.

PMID- 21869271
TI  - Automatic feature design for optical character recognition using an evolutionary
      search procedure.
AB  - An automatic evolutionary search is applied to the problem of feature extraction
      in an OCR application. A performance measure based on feature independence is
      used to generate features which do not appear to suffer from peaking effects
      [17]. Features are extracted from a training set of 30 600 machine printed 34
      class alphanumeric characters derived from British mail. Classification results
      on the training set and a test set of 10 200 characters are reported for an
      increasing number of features. A 1.01 percent forced decision error rate is
      obtained on the test data using 316 features. The hardware implementation should
      be cheap and fast to operate. The performance compares favorably with current low
      cost OCR page readers.

PMID- 21869272
TI  - Monotonicity of linear separability under translation.
AB  - A set of n pattern vectors are given in d-space and classified arbitrarily into
      two sets. The sets of patterns are said to be linearly separable if there exists
      a hyperplane that separates them. We ask whether translation of one of these sets
      in an arbitrary direction helps separability. Sometimes yes and sometimes no, but
      yes on the average. The average is taken over all classifications of the patterns
      into two sets. In fact, we prove that the probability of separability increases
      as the translation increases. Thus, we conclude that if points are drawn
      equiprobably from densities fo(x) and f1(x) = fo(x + tw) then the probability of
      linear separability is minimum at t = 0 and increases with t for t > 0.

PMID- 21869273
TI  - On the effect of noise on the moore-penrose generalized inverse associative
      memory.
AB  - Monte Carlo simulations of the continuous Moore-Penrose generalized inverse
      associative memory (Kohonen [l]) have shown that the noise-to-signal ratio is
      improved on recall in the autoassociative case as long as the number of vector
      pairs stored is less than the number of components per vector. In the
      heteroassociative case, however, the noise-to-signal ratio may actually be
      greatly increased upon recall, particularly as the number of vector pairs stored
      approaches the number of components per vector. The increase in output noise-to
      signal ratio in the heteroassociative case is found to be due to the fact that
      the inverse of the product of the key vector matrix with its transpose may
      increase without bound in spite of the fact that the key vectors are linearly
      independent.

PMID- 21869274
TI  - Data structures in kernel density estimation.
AB  - We analyze and compare several data structures and algorithms for evaluating the
      kernel density estimate. Frequent evaluations of this estimate are for example
      needed for plotting, error estimation, Monte Carlo estimation of probabilities
      and functionals, and pattern classification. An experimental comparison is
      included.

PMID- 21869275
TI  - A loose-pattern process approach to clustering fuzzy data sets.
AB  - A loose-pattern process approach to clustering sets consists of three main
      computations: loose-pattern reject option, tight-pattern classifcation, and loose
      pattern assigning classes. The loose-pattern rejection is implemented using a
      rule based on q nearest neighbors of each point. Two clustering methods, GLC and
      OUPIC, are introduced as tight-pattern clustering techniques. The decisions of
      loose-pattern assigning classes are related to a heuristic membership function.
      The function and experiments with one set is discussed.

PMID- 21869276
TI  - Dynamic occlusion analysis in optical flow fields.
AB  - Optical flow can be used to locate dynamic occlusion boundaries in an image
      sequence. We derive an edge detection algorithm sensitive to changes in flow
      fields likely to be associated with occlusion. The algorithm is patterned after
      the Marr-Hildreth zero-crossing detectors currently used to locate boundaries in
      scalar fields. Zero-crossing detectors are extended to identify changes in
      direction and/or magnitude in a vector-valued flow field. As a result, the
      detector works for flow boundaries generated due to the relative motion of two
      overlapping surfaces, as well as the simpler case of motion parallax due to a
      sensor moving through an otherwise stationary environment. We then show how the
      approach can be extended to identify which side of a dynamic occlusion boundary
      corresponds to the occluding surface. The fundamental principal involved is that
      at an occlusion boundary, the image of the surface boundary moves with the image
      of the occluding surface. Such information is important in interpreting dynamic
      scenes. Results are demonstrated on optical flow fields automatically computed
      from real image sequences.

PMID- 21869278
TI  - Local determination of a moving contrast edge.
AB  - This paper proposes an intensity-based method for determining the spatial
      orientation and observed velocity of a continuously moving edge. Space-time
      relations arise from the translation of a straight edge across a fixed detector
      array; a tesselation unit comprised of three equidistant detectors is used to
      exploit these relationships. The time ordering of cells within this unit can
      estimate edge direction and velocity. More precise edge determination is possible
      when intercell times are available and constant edge velocity is assumed; a
      sensitivity analysis examines the effect of relaxing the velocity constraint. The
      simulation of a translating synthetic image over an array of detectors is
      presented in order to demonstrate the method.

PMID- 21869277
TI  - Determining three-dimensional motion and structure from optical flow generated by
      several moving objects.
AB  - A new approach for the interpretation of optical flow fields is presented. The
      flow field, which can be produced by a sensor moving through an environment with
      several independently moving, rigid objects, is allowed to be sparse, noisy, and
      partially incorrect. The approach is based on two main stages. In the first
      stage, the flow field is partitioned into connected segments of flow vectors,
      where each segment is consistent with a rigid motion of a roughly planar surface.
      In the second stage, segments are grouped under the hypothesis that they are
      induced by a single, rigidly moving object. Each hypothesis is tested by
      searching for three-dimensional (3-D) motion parameters which are compatible with
      all the segments in the corresponding group. Once the motion parameters are
      recovered, the relative environmental depth can be estimated as well. Experiments
      based on real and simulated data are presented.

PMID- 21869279
TI  - Recognizing partially occluded parts.
AB  - The problem of recognizing an object from a partially occluded boundary image is
      considered, and the concept of saliency of a boundary segment is introduced.
      Saliency measures the extent to which the boundary segment distinguishes the
      object to which it belongs from other objects which might be present. An
      algorithm is presented which optimally determines the saliency of boundary
      segments of one object with respect to those of a set of other objects. An
      efficient template matching algorithm using templates weighted by boundary
      segment saliency is then presented and employed to recognize partially occluded
      parts. The results of these experiments illustrate the effectiveness of the new
      technique.

PMID- 21869280
TI  - Connected line drawing extraction from a perspective view of a polyhedron.
AB  - To extract line drawings with positional information from perspective veiws of
      three-dimensional objects is essential in image analysis and understanding. A new
      heuristic-search algorithm driven by a priori knowledge contained in a world
      model is presented which extracts a connected line drawing from a perspective
      view of a polyhedron. A main feature of our algorithm is that the search is
      concentrated on local areas centered at corners found with a corner finder.
      Therefore, the search time is significantly reduced and so are the positional
      errors in the extracted line drawing. An iterative process removes the false
      corners and lines and thus guarantees that our algorithm will work stably and
      reliably even in a noisy environment. Experimental results are presented.

PMID- 21869281
TI  - Knowledge-driven ultrasonic three-dimensional organ modeling.
AB  - A representation is described for nonstructured biologic objects which are single
      valued distortions of a sphere. The representation is implemented in a model
      driven system for extracting three-dimensional (3-D) organ reconstructions from a
      series of arbitrarily oriented ultrasound slices. A training set of ultrasonic
      reconstructions of similarly shaped objects is used to give the computer generic
      knowledge of a given shape class. This knowledge is in the form of local slope
      constraints defined on an object coordinate system. The combination of
      constraints, interacting together via a relaxation process on continuous label
      sets, attempts to capture the essential shape and range of variation for an organ
      class. An initial tolerance region and ''bestguess'' organ surface are
      established by the interaction of the learned shape knowledge with manually input
      organ landmarks. A hypothesize-verify paradigm is employed to alternately request
      new data and to update the tolerance region and bestguess surface. Examples from
      runs on two balloon classes are presented. These examples show: 1) the local
      constraints interact to produce a reasonable global depiction of the essential
      shape and range of variation, 2) the use of shape knowledge permits accurate
      results from only one third of the available data, and 3) the 3-D shape knowledge
      provides a two-dimensional (2-D) tolerance region for plan-guided edge detection.

PMID- 21869282
TI  - Parallel game-tree search.
AB  - The design issues affecting a parallel implementation of the alpha-beta search
      algorithm are discussed with emphasis on a tree decomposition scheme that is
      intended for use on well ordered trees. In particular, the principal variation
      splitting method has been implemented, and experimental results are presented
      which show how such refinements as progressive deepening, narrow window
      searching, and the use of memory tables affect the performance of multiprocessor
      based chess playing programs. When dealing with parallel processing systems,
      communication delays are perhaps the greatest source of lost time. Therefore, an
      implementation of our tree decomposition based algorithm is presented, one that
      operates with a modest amount of message passing within a network of processors.
      Since our system has low search overhead, the principal basis for comparison is
      the communication overhead, which in turn is shown to have two components.

PMID- 21869283
TI  - Attributed string matching with merging for shape recognition.
AB  - A new structural approach to shape recognition using attributed string matching
      with merging is proposed. After illustrating the disadvantages of conventional
      symbolic string matching using changes, deletions, and insertions, attributed
      strings are suggested for matching. Each attributed string is an ordered sequence
      of shape boundary primitives, each representing a basic boundary structural unit,
      line segment, with two types of numerical attributes, length and direction. A new
      type of primitive edit operation, called merge, is then introduced, which can be
      used to combine and then match any number of consecutive boundary primitives in
      one shape with those in another. The resulting attributed string matching with
      merging approach is shown useful for recognizing distorted shapes. Experimental
      results prove the feasibility of the proposed approach for general shape
      recognition. Some possible extensions of the approach are also included.

PMID- 21869284
TI  - A width-independent fast thinning algorithm.
AB  - The skeleton of a digital figure can often be regarded as a convenient
      alternative to the figure itself. It is useful both to diminish drastically the
      amount of data to be handled, and to simplify the computational procedures
      required for description and classification purposes. Thinning a digital figure
      down to its skeleton is a time-consuming process when conventional sequential
      computers are employed. The procedure we propose allows one to speed up the
      thinning transformation, and to get a well-shaped skeleton. After cleaning of the
      input picture has been performed, the pixels of the figure are labeled according
      to their distance from the background, and a set, whose pixels are symmetrically
      placed with respect to distinct contour parts of the figure, is found. This set
      is then given a linear structure by applying topology preserving removal
      operations. Finally, a pruning step, regarding branches not relevant in the
      framework of the problem domain, completes the process. The resulting skeleton is
      a labeled set of pixels which is shown to possess all the required properties,
      particularly those concerning connectedness, topology, and shape. Moreover, the
      original figure can almost completely be recovered by means of a reverse distance
      transformation. Only a fixed and small number of sequential passes through the
      picture is necessary to achieve the goal. The computational effort is rather
      modest, and the use of the proposed algorithm turns out to be more advantageous
      the greater the width of the figure to be thinned.

PMID- 21869286
TI  - Sensing error for a mobile robot using line navigation.
AB  - The use of a contrasting line for the visual navigation of autonomous mobile
      robots in a factory environment is developed. Minimum and maximum linewidths are
      determined analytically by considering sensor geometry, field of view, and error
      conditions present in the system. The effects of these error conditions on the
      width of the line, as seen in the image plane, determines the optimal linewidth.
      Numerical examples using typical sensor parameters are given.

PMID- 21869285
TI  - Restoration of multichannel microwave radiometric images.
AB  - A constrained iterative image restoration method is applied to multichannel
      diffraction-limited imagery. This method is based on the Gerchberg-Papoulis
      algorithm utilizing incomplete information and partial constraints. The procedure
      is described using the orthogonal projection operators which project onto two
      prescribed subspaces iteratively. Its properties and limitations are presented.
      The effect of noise was investigated and a better understanding of the
      performance of the algorithm with noisy data has been achieved. The restoration
      scheme with the selection of appropriate constraints was applied to a practical
      problem. The 6.6, 10.7, 18, and 21 GHz satellite images obtained by the scanning
      multichannel microwave radiometer (SMMR), each having different spatial
      resolution, were restored to a common, high resolution (that of the 37 GHz
      channels) to demonstrate the effectiveness of the method. Both simulated data and
      real data were used in this study. The restored multichannel images may be
      utilized to retrieve rainfall distributions.

PMID- 21869287
TI  - Reliability and speed of recall in an associative network.
AB  - Previous investigations of the storage capacity of associative nets have not
      explicitly considered quantitative aspects of the tradeoff between storage
      capacity and reconstructive power in these systems. Furthermore, few comparisons
      have been made between theoretical estimates and experimental results
      (simulations). In this correspondence, we describe some results recently obtained
      and relevant to these issues. It is shown that a high storage capacity is
      possible, without sacrificing reliability in the recall process. Furthermore, an
      efficient algorithm for retrieval of the information stored is presented, and the
      speed of recall employing various degrees of parallelism is discussed.

PMID- 21869288
TI  - A knowledge-based approach to design.
AB  - A framework is presented for constructing knowledge-based aids for design
      problems. In particular, we describe the organization of an interactive knowledge
      based consultant for VLSI design (called VEXED?an acronym for VLSI expert
      editor), and a prototype implementation of VEXED. The paper focuses on the
      principles underlying the design of VEXED, and on several lessons and research
      issues that have arisen from implementing and experimenting with this prototype.

PMID- 21869289
TI  - Strategies for knowledge acquisition.
AB  - This paper describes knowledge acquisition strategies developed in the course of
      handcrafting a diagnostic system and reports on their consequent implementation
      in MORE, an automated knowledge acquisition system. We describe MORE in some
      detail, focusing on its representation of domain knowledge, rule generation
      capabilities, and interviewing techniques. MORE's approach is shown to embody
      methods which may prove fruitful to the development of knowledge acquisition
      systems in other domains.

PMID- 21869290
TI  - Gradualness facilitates knowledge refinement.
AB  - To facilitate knowledge refinement, a system should be designed so that small
      changes in the knowledge correspond to small changes in the function or
      performance of the system. Two sets of experiments show the value of small,
      heuristically guided changes in a weighted rule base. In the first set, the
      ordering among numbers (reflecting certainties) makes their manipulation more
      straightforward than the manipulation of relationships. A simple credit
      assignment and weight adjustment strategy for improving numbers in a weighted,
      rule-based expert system is presented. In the second set, the rearrangement of
      predicates benefits from additional knowledge about the ''ordering'' among
      predicates. A third set of experiments indicates the importance of the proper
      level of granularity when augmenting a knowledge base. Augmentation of one
      knowledge base by analogical reasoning from another knowledge base did not work
      with only binary relationships, but did succeed with ternary relationships. To
      obtain a small improvement in the knowledge base, a substantial amount of
      structure had to be treated as a unit.

PMID- 21869291
TI  - Representation of activity knowledge for project management.
AB  - Representation of activity knowledge is important to any application which must
      reason about activities such as new product management, factory scheduling, robot
      control, vehicle control, software engineering, and air traffic control. This
      paper provides an integration of the underlying theories needed for modeling
      activities. Using the domain of large computer design projects as an example, the
      semantics of activity modeling is described. While the past research in knowledge
      representation has discovered most of the underlying concepts, our attempt is
      toward their integration. This includes the epistemological concepts for erecting
      the required knowledge structure; the concepts of activity, state, goal, and
      manifestation for the adequate description of the plan and the progress; and the
      concepts of time and causality to infer the progression among the activities. We
      also address the issues which arise due to the integration of aggregation, time,
      and causality among activities and states.

PMID- 21869292
TI  - A general expert system design for diagnostic problem solving.
AB  - Existing expert systems have a high percentage agreement with experts in a
      particular field in many situations. However, in many ways their overall behavior
      is not like that of a human expert. These areas include the inability to give
      flexible, functional explanations of their reasoning processes, and the failure
      to degrade gracefully when dealing with problems at the periphery of their
      knowledge. These two important shortcomings can be improved when the right
      knowledge is available to the system. This paper presents an expert system
      design, called the integrated diagnostic model (IDM), that integrates two sources
      of knowledge, a shallow, reasoning-oriented, experiential knowledge base and a
      deep, functionally oriented, physical knowledge base. To demonstrate the IDM's
      usefulness in the problem area of diagnosis and repair, an implementation in the
      mechanical domain is described.

PMID- 21869293
TI  - R1-soar: an experiment in knowledge-intensive programming in a problem-solving
      architecture.
AB  - This paper presents an experiment in knowledge-intensive programming within a
      general problem-solving production-system architecture called Soar. In Soar,
      knowledge is encoded within a set of problem spaces, which yields a system
      capable of reasoning from first principles. Expertise consists of additional
      rules that guide complex problem-space searches and substitute for expensive
      problem-space operators. The resulting system uses both knowledge and search when
      relevant. Expertise knowledge is acquired either by having it programmed, or by a
      chunking mechanism that automatically learns new rules reflecting the results
      implicit in the knowledge of the problem spaces. The approach is demonstrated on
      the computer-system configuration task, the task performed by the expert system
      R1.

PMID- 21869294
TI  - Rule-based interpretation of aerial imagery.
AB  - In this paper, we describe the organization of a rule-based system, SPAM, that
      uses map and domain-specific knowledge to interpret airport scenes. This research
      investigates the use of a rule-based system for the control of image processing
      and interpretation of results with respect to a world model, as well as the
      representation of the world model within an image/map database. We present
      results on the interpretation of a high-resolution airport scene wvhere the image
      segmentation has been performed by a human, and by a region-based image
      segmentation program. The results of the system's analysis is characterized by
      the labeling of individual regions in the image and the collection of these
      regions into consistent interpretations of the major components of an airport
      model. These interpretations are ranked on the basis of their overall spatial and
      structural consistency. Some evaluations based on the results from three
      evolutionary versions of SPAM are presented.

PMID- 21869295
TI  - An approach to expert control of interactive software systems.
AB  - Expert problem-solving strategies in many domains require the use of detailed
      mathematical techniques coupled with experiential knowledge about how and when to
      use the appropriate techniques. In many of these domains, such techniques are
      made available to experts in large software packages. In attempting to build
      expert systems for these domains, we wish to make use of these packages, and are
      therefore faced with an important problem: how to integrate the existing
      software, and knowledge about its use, into a practical expert system. The expert
      knowledge is used, in dynamic selection and interpretation of appropriate
      programs and parameters, to reach a successful goal in the problem solving. We
      describe the framework of a hybrid expert system for representing problem-solving
      knowledge in these domains. This hybrid system may be characterized as consisting
      of a production system and mathematical methods. The software package is
      reorganized as necessary to map it into the mathematical-method representation of
      a hybrid system. This approach has evolved out of an effort to build an expert
      system for performing well-log analysis, ELAS (expert log analysis system).

PMID- 21869296
TI  - Conceptual clustering in knowledge organization.
AB  - Knowledge organization is a very important step in building an expert system. The
      problem is how to organize knowledge into a conceptual structure and thus make it
      complete, concise, and consistent. In this paper, concepts used in knowledge
      description are divided into tangible ones and intermediate ones depending on
      whether or not they appear in the input or the output of the system. Intermediate
      concepts and their relationships with tangible concepts are subjected to changes.
      A distance measure for rules and an algorithm for conceptual clustering are
      described. New intermediate concepts are generated using this algorithm. A few
      new concepts may replace a large number of old relationships and also generate
      new rules for the system. An experiment on traditional Chinese medicine shows
      that the proposed method produces results similar to those generated by experts.

PMID- 21869297
TI  - Entropy and distance of random graphs with application to structural pattern
      recognition.
AB  - The notion of a random graph is formally defined. It deals with both the
      probabilistic and the structural aspects of relational data. By interpreting an
      ensemble of attributed graphs as the outcomes of a random graph, we can use its
      lower order distribution to characterize the ensemble. To reflect the variability
      of a random graph, Shannon's entropy measure is used. To synthesize an ensemble
      of attributed graphs into the distribution of a random graph (or a set of
      distributions), we propose a distance measure between random graphs based on the
      minimum change of entropy before and after their merging. When the ensemble
      contains more than one class of pattern graphs, the synthesis process yields
      distributions corresponding to various classes. This process corresponds to
      unsupervised learning in pattern classification. Using the maximum likelihood
      rule and the probability computed for the pattern graph, based on its matching
      with the random graph distributions of different classes, we can classify the
      pattern graph to a class.

PMID- 21869298
TI  - Geometric reconstruction of buried heat sources from a surface thermogram.
AB  - Attempts to reconstruct the spatial location, size, and form of buried heat
      sources from the measured pattern of thermograms are, in general, prohibited by
      the lack of a priori information about the thermal (flow) model and the source
      structure. In this paper, a method is introduced based on geometric
      reconstruction of a buried heat source configuration. This configuration must
      contain point sources and/or sharp edges and be confined to a plane region
      parallel to the surface. The medium, in which the heat source is embedded, is
      assumed to be homogeneous, isotropic, and of large size compared to the size of
      the source and to its depth below the surface. The heat flux from the surface to
      the ambient is assumed to follow the Newtonian cooling law. The spatial density
      distribution of the flux can be described by a Green function with coefficients
      determined by the depth of the source plane. It is possible to approximate a
      corresponding inverse mapping algorithm (reconstruction filter) for each source
      plane depth, with only one (depth) scaling parameter. The density distribution of
      the source structure is optimally deblurred when the reconstruction filter's
      scaling parameter matches the actual depth of the source plane below the surface.
      In the reconstruction procedure, this reconstruction filter is consecutively
      applied for several values of the scaling parameter. The so-called ''deblurring
      quality'' of the point or edge information is utilized to decide which scaling
      parameter achieves the sharpest image. This procedure resembles the focusing of a
      lens.

PMID- 21869299
TI  - Relaxation matching techniques-a comparison.
AB  - Many different relaxation schemes have been proposed for image analysis tasks. We
      have developed a general matching procedure for comparing semantic network
      descriptions of images, and we have implemented a variety of relaxation
      techniques. An automatic segmentation and description system is used to produce
      the image representations so that the matching procedures must cope with
      variations in feature values, missing objects, and possible multiple matches.
      This environment is used to test different relaxation matching schemes under a
      variety of conditions. The best performance (of those we compared), in terms of
      the number of iterations and the number of errors, is for the gradient-based
      optimization approach of Faugeras and Price. The related optimization approach of
      Hummel and Zucker performed almost as well, with differences primarily in
      difficult matches (i.e., where much of the evidence is against the match, for
      instance, poor segmentations). The product combination rule proposed by Peleg was
      extremely fast, indeed, too fast to work when global context is needed. The
      classical Rosenfeld, Hummel, and Zucker method is included for historical
      comparisons and performed only adequately, producing fewer correct matches and
      taking more iterations.

PMID- 21869300
TI  - Distributed computing for vision: architecture and a benchmark test.
AB  - Computer vision algorithms are notorious for their computational expense.
      Distributed vision, the use of more than one processor, can decrease computation
      costs and speed up algorithms. There are various ways to do this, ranging from
      parallelism at the sensor level to true multiprocessor systems. This
      correspondence first describes a system of the latter type: a system of
      microprocessors on a high-speed bus. A canonical vision task, locating a number
      of objects and measuring certain two-dimensional features of those objects,
      serves as a benchmark test for the system. An algorithm for this task is
      presented. Performance measures are compared from implementations on the
      distributed system, a Vax 11/750, and a Vax 11/780. Results indicate that three
      microprocessors outperform a Vax 11/780 at this task. Finally, other more
      interesting distributed algorithms are briefly discussed.

PMID- 21869301
TI  - Experiments in intensity guided range sensing recognition of three-dimensional
      objects.
AB  - With the advent of devices that can directly sense and determine the coordinates
      of points in space, the goal of constructing and recognizing descriptors of three
      dimensional (3-D) objects is attracting the attention of many researchers in the
      image processing community. Unfortunately, the time required to fully sense a
      range image is large relative to the time required to sense an intensity image.
      Conversely, a single intensity image lacks the depth information required to
      construct 3-D object descriptors. This paper presents a method of combining the
      two sensory sources, intensity and range, such that the time required for range
      sensing is considerably reduced. The approach is to extract potential points of
      interest from the intensity image and then selectively sense range at these
      feature points. After the range information is known at these points, a graph
      structure representing the object in the scene is constructed. This structure is
      compared to the stored graph models using an algorithm for partial matching. The
      results of applying the method to both synthetic data and real intensity/range
      images are presented.

PMID- 21869302
TI  - New fusion operations for digitized binary images and their applications.
AB  - This paper proposes a new class of fusion operations which are useful for binary
      image processing. To begin with, an algorithm for the classical fusion operations
      is presented. They are sequentially composed of two basic operations, that is,
      expansion and contraction. The strategy of the proposed algorithm is as follows:
      the first operation is performed with the distance transformation, and the second
      operation utilizes the distance information obtained in the first operation.
      Next, a topological contraction and a topological expansion are defined. The
      topological contraction preserves the Euler number of an input image except that
      some simply connected components of 1 pixels are erased. The topological
      expansion preserves the Euler number of an input image except that some simply
      connected holes are filled. Then, several new fusion operations are obtained by
      combining the classical contraction and the topological expansion (or, the
      classical expansion and the topological contraction) sequentially. The algorithms
      for them use the same strategy as the proposed algorithm for the classical fusion
      operations. Finally, experimental results show that the new fusion operations and
      their combinations are effectively used in the binary image processing, such as
      shape smoothing, merging and separating connected components, and structure
      analysis.

PMID- 21869303
TI  - Applications of quadtree, octree, and binary tree decomposition techniques to
      shape analysis and pattern recognition.
AB  - The binary tree, quadtree, and octree decomposition techniques are widely used in
      computer graphics and image processing problems. Here, the techniques are
      reexamined for pattern recognition and shape analysis applications. It has been
      shown that the quadtree and octree techniques can be used to find the shape hull
      of a set of points in space while their n-dimensional generalization can be used
      for divisive hierarchical clustering. Similarly, an n-dimensional binary tree
      decomposition of feature space can be used for efficient pattern classifier
      design. Illustrative examples are presented to show the usefulness and efficiency
      of these hierarchical decomposition techniques.

PMID- 21869304
TI  - Applications of tensor theory to object recognition and orientation
      determination.
AB  - A method is developed by which images resulting from orthogonal projection of
      rigid planar-patch objects arbitrarily oriented in three-dimensional (3-D) space
      may be used to form systems of linear equations which are solved for the affine
      transform relating the images. The technique is applicable to complete images and
      to unlabeled feature sets derived from images, and with small modification may be
      used to transform images of unknown objects such that they represent images of
      those objects from a known orientation, for use in object identification. No
      knowledge of point correspondence between images is required. Theoretical
      development of the method and experimental results are presented. The method is
      shown to be computationally efficient, requiring O(N) multiplications and
      additions where, depending on the computation algorithm, N may equal the number
      of object or edge picture elements.

PMID- 21869305
TI  - Uniform resampling of digitized contours.
AB  - This paper addresses the problem of the nonuniform intersample distance of
      digital curves obtained as a result of quantization of continuous contours on a
      square lattice. A resampling algorithm based on variable-factor interpolation and
      decimation is presented, and its performance is evaluated analytically and by
      computer simulations assuming the grid-intersect quantization. It is shown that
      the output of the resampling algorithm outperforms the original digital curve in
      terms of the average and maximum error in the measurement of length by 50 and 73
      percent, respectively. The resampling algorithm can be used as a preprocessing
      stage in shape analysis systems to enhance their performance by increasing the
      accuracy and consistency of both local and global features such as curvature and
      the Fourier shape descriptors.

PMID- 21869306
TI  - Intelligent backtracking in plan-based deduction.
AB  - This paper develops a method of mechanical deduction based on a graphical
      representation of the structure of proofs. Attempts to find a refutation(s) are
      recorded in the form of plans, corresponding to portions of an AND/OR graph
      search space and representing a purely deductive structure of derivation. This
      method can be applied to any initial base (set of nonnecessarily Horn clauses).
      Unlike the exhaustive (blind) backtracking which treats all the goals deduced in
      the course of a proof as equally probable sources of failure, his approach
      detects the exact source of failure. Only a small fragment of the solution space
      is kept on disk as a collection of pairs, each of which consists of a plan and a
      graph of constraints. The search strategy and the method of nonredundant
      processing of individual pairs which leads to a solution (if it exists) is
      presented. This approach is compared?on a special case?with a blind backtracking
      algorithm for which an exponential improvement is demonstrated. Some important
      implementation problems are discussed, and toplevel design of a mechanical
      deduction system implementing our algorithm is presented. It is proven that the
      algorithm is complete in the following sense: if for a given base a resolution
      refutation exists, then this refutation is found by the algorithm.

PMID- 21869307
TI  - Incorporating fuzzy membership functions into the perceptron algorithm.
AB  - The perceptron algorithm, one of the class of gradient descent techniques, has
      been widely used in pattern recognition to determine linear decision boundaries.
      While this algorithm is guaranteed to converge to a separating hyperplane if the
      data are linearly separable, it exhibits erratic behavior if the data are not
      linearly separable. Fuzzy set theory is introduced into the perceptron algorithm
      to produce a ''fuzzy algorithm'' which ameliorates the convergence problem in the
      nonseparable case. It is shown that the fuzzy perceptron, like its crisp
      counterpart, converges in the separable case. A method of generating membership
      functions is developed, and experimental results comparing the crisp to the fuzzy
      perceptron are presented.

PMID- 21869308
TI  - The first stage in two-stage template matching.
AB  - This paper formulates the problem encountered in the first stage of two-stage,
      binary template matching as a set of hypotheses to be tested, including a
      hypothesis of ''no object.'' Two new statistics R and G are proposed, based on a
      likelihood ratio, and are compared to the sum of absolute differences and a
      correlation measure by analytical approximations and Monte Carlo experiments.
      Statistical power and a measure of sensitivity to the true location of the object
      are the criteria. Parameters are the numbers of 1's in object and image,
      subtemplate size, and parameters reflecting intensity distortion between template
      and object. One of the proposed statistics R is much more computationally
      intensive than the other G. Although R is more powerful than G and the other
      statistics, G is generally more sensitive to the true object location. Statistic
      G is also more powerful than the sum of absolute differences and correlation. All
      statistics are robust to incomplete knowledge of distortion parameters.
      Experiments on Landsat images confirm the sensitivity of G and recommend it for
      application in the first stage.

PMID- 21869309
TI  - On the recognition of properties of three-dimensional pictures.
AB  - This correspondence proposes one-pass algorithms that compute the numbers of
      objects, cavities, and holes in three-dimensional (3-D) digital pictures. Also,
      it is shown that a one-way, 3-D parallel/sequential acceptor cannot accept the
      class of 3-D binary arrays in which the set of 1's is connected, unlike the
      situation in the two-dimensional (2-D) case; but it can do so if multipasses are
      allowed.

PMID- 21869310
TI  - Recognition of moving objects using feature signatures.
AB  - An important application of machine vision systems is the recognition of known
      three-dimensional objects. A major difficulty arises when two or more objects
      project the same or similar two-dimensional image, often resulting in
      misclassification and degradation of system performance. The changes in images
      which result from the motion of objects provide a source of three-dimensional
      information which can greatly aid the classification process, but this three
      dimensional analysis is computationally complex and subject to many sources of
      error. This work develops a methodology which utilizes the information derived
      from the apparent changes in object features over time to facilitate the
      recognition task, without the need to actually recover the three-dimensional
      structure of the objects under view. The basic approach is to generate a
      ''feature signature'' by combining the feature measurements of the individual
      regions in a long sequence of images. The static information in the individual
      frames is analyzed along with the temporal information from the entire sequence.
      These techniques are particularly applicable in situations where static image
      processing methods cannot discriminate between ambiguous objects. Two example
      implementations are presented to illustrate the application of the techniques of
      object recognition using motion information.

PMID- 21869311
TI  - A model for the analysis of neighbor finding in pointer-based quadtrees.
AB  - A natural byproduct of the tree-like nature of the quadtree is that many basic
      image processing operations can be implemented as tree traversals which differ in
      the nature of the computation that is performed at each node. Some of these
      computations involve the inspection of a node's adjacent neighbors (termed
      neighbor finding). A new model is developed for images represented by quadtrees,
      and it is used to analyze various neighbor-finding techniques. The model's
      predicted costs for neighbor finding correlate very closely with empirical
      results and it is superior to the model that was used previously.

PMID- 21869312
TI  - Describing a Robot's Workspace Using a Sequence of Views from a Moving Camera.
AB  - This correspondence describes a method of building and maintaining a spatial
      respresentation for the workspace of a robot, using a sensor that moves about in
      the world. From the known camera position at which an image is obtained, and two
      dimensional silhouettes of the image, a series of cones is projected to describe
      the possible positions of the objects in the space. When an object is seen from
      several viewpoints, the intersections of the cones constrain the position and
      size of the object. After several views have been processed, the representation
      of the object begins to resemble its true shape. At all times, the spatial
      representation contains the best guess at the true situation in the world with
      uncertainties in position and shape explicitly represented. An octree is used as
      the data structure for the representation. It not only provides a relatively
      compact representation, but also allows fast access to information and enables
      large parts of the workspace to be ignored. The purpose of constructing this
      representation is not so much to recognize objects as to describe the volumes in
      the workspace that are occupied and those that are empty. This enables trajectory
      planning to be carried out, and also provides a means of spatially indexing
      objects without needing to represent the objects at an extremely fine resolution.
      The spatial representation is one part of a more complex representation of the
      workspace used by the sensory system of a robot manipulator in understanding its
      environment.

PMID- 21869313
TI  - Shape information from rotated scans.
AB  - In many proposed applications, robots are required to recognize a relatively
      small number of object types, each well defined by shape. In such cases,
      relatively simple pattern recognition methods may be adequate. This paper
      presents a number of exceptionally simple shape discrimination algorithms which
      exploit the particularly covenient data provided by the combination of a rotating
      camera and analog edge finder proposed by Miller and Boie.

PMID- 21869314
TI  - Min-max operators in texture analysis.
AB  - A signature is generated for a given picture by operating on it with different
      masks. The operations are gray level generalizations of ''shrink'' and ''expand''
      for binary pictures using Serra's morphological methods [10]. The signature is a
      set of numbers, each corresponding to an application of an operator at a certain
      scale and direction, and can be used to analyze the discriminate textures. It is
      shown that this family of signatures includes as special cases several currently
      used texture descriptors.

PMID- 21869315
TI  - Surface curvature as a measure of image texture.
AB  - Methods from the theory of surfaces in differential geometry are applied to the
      gray tone intensity and absorbance surfaces defined by a digital image. In
      particular, the first fundamental form, the second fundamental form, the two
      principal curvatures, the Gaussian curvature, and mean curvature from classical
      differential geometry are presented. New curvatures are introduced which appear
      to be more appropriate for the purposes of image texture. For each curvature, a
      texture feature is generated. These features are applied to biological cell
      nuclei and it is found that they are useful for purposes of discrimination.

PMID- 21869316
TI  - Description and discrimination of planar shapes using shape matrices.
AB  - A shape descriptor has been developed which can describe a shape independent of
      its translation, rotation, and scaling. The description is in the form of a
      matrix and it is obtained by a polar quantization of a shape. The quantization
      process takes into consideration not only a shape's outer geometry but its inner
      geometry as well. The descriptor is information preserving and if the
      quantization parameters are selected properly, it is possible to reconstruct an
      original shape from its description. In this technique, shape discrimination is
      possible by a simple EXCLUSIVE-OR operation on shape descriptions.

PMID- 21869317
TI  - A cognitive heuristic algorithm for reseau mark detection by hill climbing.
AB  - A hill-climbing approach for the automatic detection of Reseau marks (RM) on the
      vidicon type of imagery is presented. This procedure is based on the minimization
      of a figure of merit which is a measure of the clustering nature of the gray
      values of the Reseau pixels around a nominal value. The often-encountered problem
      of false detection is circumvented by incorporating the concept of ''learning''
      the mean gray value of the RM pixels. Results of applying the algorithm to both
      synthetic and actual imagery demonstrate the efficacy of the proposed method.

PMID- 21869318
TI  - The curvature primal sketch.
AB  - In this paper we introduce a novel representation of the significant changes in
      curvature along the bounding contour of planar shape. We call the representation
      the Curvature Primal Sketch because of the close analogy to the primal sketch
      representation advocated by Marr for describing significant intensity changes. We
      define a set of primitive parameterized curvature discontinuities, and derive
      expressions for their convolutions with the first and second derivatives of a
      Gaussian. We describe an implemented algorithm that computes the Curvature Primal
      Sketch by matching the multiscale convolutions of a shape, and illustrate its
      performance on a set of tool shapes. Several applications of the representation
      are sketched.

PMID- 21869319
TI  - Scaling theorems for zero crossings.
AB  - We characterize some properties of the zero crossings of the Laplacian of
      signals?in particular images?filtered with linear filters, as a function of the
      scale of the filter (extending recent work by Witkin [16]). We prove that in any
      dimension the only filter that does not create generic zero crossings as the
      scale increases is the Gaussian. This result can be generalized to apply to level
      crossings of any linear differential operator: it applies in particular to ridges
      and ravines in the image intensity. In the case of the second derivative along
      the gradient, there is no filter that avoids creation of zero crossings, unless
      the filtering is performed after the derivative is applied.

PMID- 21869320
TI  - Uniqueness of the gaussian kernel for scale-space filtering.
AB  - Scale-space filtering constructs hierarchic symbolic signal descriptions by
      transforming the signal into a continuum of versions of the original signal
      convolved with a kernal containing a scale or bandwidth parameter. It is shown
      that the Gaussian probability density function is the only kernel in a broad
      class for which first-order maxima and minima, respectively, increase and
      decrease when the bandwidth of the filter is increased. The consequences of this
      result are explored when the signal?or its image by a linear differential
      operator?is analyzed in terms of zero-crossing contours of the transform in scale
      space.

PMID- 21869321
TI  - Scale-based description and recognition of planar curves and two-dimensional
      shapes.
AB  - The problem of finding a description, at varying levels of detail, for planar
      curves and matching two such descriptions is posed and solved in this paper. A
      number of necessary criteria are imposed on any candidate solution method. Path
      based Gaussian smoothing techniques are applied to the curve to find zeros of
      curvature at varying levels of detail. The result is the ''generalized scale
      space'' image of a planar curve which is invariant under rotation, uniform
      scaling and translation of the curve. These properties make the scale space image
      suitable for matching. The matching algorithm is a modification of the uniform
      cost algorithm and finds the lowest cost match of contours in the scale space
      images. It is argued that this is preferable to matching in a so-called stable
      scale of the curve because no such scale may exist for a given curve. This
      technique is applied to register a Landsat satellite image of the Strait of
      Georgia, B.C. (manually corrected for skew) to a map containing the shorelines of
      an overlapping area.

PMID- 21869322
TI  - HYPER: A New Approach for the Recognition and Positioning of Two-Dimensional
      Objects.
AB  - A new method has been designed to identify and locate objects lying on a flat
      surface. The merit of the approach is to provide strong robustness to partial
      occlusions (due for instance to uneven lighting conditions, shadows, highlights,
      touching and overlapping objects) thanks to a local and compact description of
      the objects boundaries and to a new fast recognition method involving generation
      and recursive evaluation of hypotheses named HYPER (HY potheses Predicted and
      Evaluated Recursively). The method has been integrated within a vision system
      coupled to an indutrial robot arm, to provide automatic picking and repositioning
      of partially overlapping industrial parts.

PMID- 21869323
TI  - An autoregressive model approach to two-dimensional shape classification.
AB  - In this paper, a method of classifying objects is reported that is based on the
      use of autoregressive (AR) model parameters which represent the shapes of
      boundaries detected in digitized binary images of the objects. The object
      identification technique is insensitive to object size and orientation. Three
      pattern recognition algorithms that assign object names to unlabelled sets of AR
      model parameters were tested and the results compared. Isolated object tests were
      performed on five sets of shapes, including eight industrial shapes (mostly taken
      from the recognition literature), and recognition accuracies of 100 percent were
      obtained for all pattern sets at some model order in the range 1 to 10. Test
      results indicate the ability of the technique developed in this work to recognize
      partially occluded objects. Processing-speed measurements show that the method is
      fast in the recognition mode. The results of a number of object recognition tests
      are presented. The recognition technique was realized with Fortran programs,
      Imaging Technology, Inc. image-processing boards, and a PDP 11/60 computer. The
      computer algorithms are described.

PMID- 21869324
TI  - Optimum uniform piecewise linear approximation of planar curves.
AB  - Two-dimensional digital curves are often uniformly approximated by polygons or
      piecewise linear curves. Several algorithms have been proposed in the literature
      to find such curves. We present an algorithm that finds a piecewise linear curve
      with the minimal number of segments required to approximate a curve within a
      uniform error with fixed initial and final points. We compare our optimal
      algorithm to several suboptimal algorithms with respect to the number of linear
      segments required in the approximation and the execution time of the algorithm.

PMID- 21869325
TI  - Structural analysis of natural textures.
AB  - Many textures can be described structurally, in terms of the individual textural
      elements and their spatial relationships. This paper describes a system to
      generate useful descriptions of natural textures in these terms. The basic
      approach is to determine an initial, partial description of the elements using
      edge features. This description controls the extraction of the texture elements.
      The elements are grouped by type, and spatial relationships between elements are
      computed. The descriptions are shown to be useful for recognition of the
      textures, and for reconstruction of periodic textures.

PMID- 21869326
TI  - Estimation of object motion parameters from noisy images.
AB  - An approach is presented for the estimation of object motion parameters based on
      a sequence of noisy images. The problem considered is that of a rigid body
      undergoing unknown rotational and translational motion. The measurement data
      consists of a sequence of noisy image coordinates of two or more object
      correspondence points. By modeling the object dynamics as a function of time,
      estimates of the model parameters (including motion parameters) can be extracted
      from the data using recursive and/or batch techniques. This permits a desired
      degree of smoothing to be achieved through the use of an arbitrarily large number
      of images. Some assumptions regarding object structure are presently made.
      Results are presented for a recursive estimation procedure: the case considered
      here is that of a sequence of one dimensional images of a two dimensional object.
      Thus, the object moves in one transverse dimension, and in depth, preserving the
      fundamental ambiguity of the central projection image model (loss of depth
      information). An iterated extended Kalman filter is used for the recursive
      solution. Noise levels of 5-10 percent of the object image size are used.
      Approximate Cramer-Rao lower bounds are derived for the model parameter estimates
      as a function of object trajectory and noise level. This approach may be of use
      in situations where it is difficult to resolve large numbers of object match
      points, but relatively long sequences of images (10 to 20 or more) are available.

PMID- 21869327
TI  - Perceptual organization and curve partitioning.
AB  - In this paper we offer a critical evaluation of the partitioning (perceptual
      organization) problem, noting the extent to which it has distinct formulations
      and parameterizations. We show that most partitioning techniques can be
      characterized as variations of four distinct paradigms, and argue that any
      effective technique must satisfy two general principles. We give concrete
      substance to our general discussion by introducing new partitioning techniques
      for planar geometric curves, and present experimental results demonstrating their
      effectiveness.

PMID- 21869328
TI  - Range measurements by a mobile robot using a navigation line.
AB  - A continuous, straight-edged line is used for the visual navigation of an
      autonomous mobile robot in a factor environment. This line, which resides on the
      floor and contrasts with background, may also be used to determine range
      information. Two methods are developed for determining the range of an object in
      the sensor's field of view. The effects of various error conditions in the system
      geometry on each ranging method are determined. Equations are derived which yield
      the percent error in calculating ranges given estimates of these error
      conditions. Numerical examples using typical sensor parameters are given.

PMID- 21869329
TI  - On kineopsis and computation of structure and motion.
AB  - This correspondence deals with the computation of structure and motion of rigid
      objects in space from image positions and optical flow. A test for rigid motion
      of objects in space is introduced which yields a new formulation of the problem.
      Assuming a central projection model for the viewing system, it is shown that
      image positions and optical flow at four points can achieve this perception.

PMID- 21869330
TI  - A pattern description and generation method of structural characters.
AB  - We report a pattern description and generation method of structural characters,
      and show some examples of Chinese and Korean character patterns actually
      generated. We also consider its educational and graphical applications. In this
      method, any character is regarded as a composite pattern constructed by several
      simpler subpatterns, and is described in terms of them by introducing three kinds
      of positional relationships among them. A composite pattern can become a
      subpattern, too. We call these patterns blocks. Syntactic grammar is defined to
      encode a pattern expression by two code strings, that is, a string of blocks and
      a string of production rules. They are used in generating patterns, namely,
      derivation of pattern expression from the code strings is defined as a process of
      pattern generation. By this description and generation method, we can encode
      structural characters without much memory, and generate natural shapes of
      patterns.

PMID- 21869331
TI  - Sum and difference histograms for texture classification.
AB  - The sum and difference of two random variables with same variances are
      decorrelated and define the principal axes of their associated joint probability
      function. Therefore, sum and difference histograms are introduced as an
      alternative to the usual co-occurrence matrices used for texture analysis. Two
      maximum likelihood texture classifiers are presented depending on the type of
      object used for texture characterization (sum and difference histograms or some
      associated global measures). Experimental results indicate that sum and
      difference histograms used conjointly are nearly as powerful as cooccurrence
      matrices for texture discrimination. The advantage of the proposed texture
      analysis method over the conventional spatial gray level dependence method is the
      decrease in computation time and memory storage.

PMID- 21869332
TI  - Image analysis using multigrid relaxation methods.
AB  - Image analysis problems, posed mathematically as variational principles or as
      partial differential equations, are amenable to numerical solution by relaxation
      algorithms that are local, iterative, and often parallel. Although they are well
      suited structurally for implementation on massively parallel, locally
      interconnected computational architectures, such distributed algorithms are
      seriously handi capped by an inherent inefficiency at propagating constraints
      between widely separated processing elements. Hence, they converge extremely
      slowly when confronted by the large representations of early vision. Application
      of multigrid methods can overcome this drawback, as we showed in previous work on
      3-D surface reconstruction. In this paper, we develop multiresolution iterative
      algorithms for computing lightness, shape-from-shading, and optical flow, and we
      examine the efficiency of these algorithms using synthetic image inputs. The
      multigrid methodology that we describe is broadly applicable in early vision.
      Notably, it is an appealing strategy to use in conjunction with regularization
      analysis for the efficient solution of a wide range of ill-posed image analysis
      problems.

PMID- 21869333
TI  - Image structure representation and processing: a discussion of some segmentation
      methods in cytology.
AB  - Image processing methods (segmentation) are presented in connection with a
      modeling of image structure. An image is represented as a set of primitives,
      characterized by their type, abstraction level, and a list of attributes.
      Entities (regions for example) are then described as a subset of primitives
      obeying particular rules. Image segmentation methods are discussed, according to
      the associated image modeling level. Their potential efficacity is compared, when
      applied to cytologic image analysis.

PMID- 21869334
TI  - On edge detection.
AB  - Edge detection is the process that attempts to characterize the intensity changes
      in the image in terms of the physical processes that have originated them. A
      critical, intermediate goal of edge detection is the detection and
      characterization of significant intensity changes. This paper discusses this part
      of the edge detection problem. To characterize the types of intensity changes
      derivatives of different types, and possibly different scales, are needed. Thus,
      we consider this part of edge detection as a problem in numerical
      differentiation. We show that numerical differentiation of images is an ill-posed
      problem in the sense of Hadamard. Differentiation needs to be regularized by a
      regularizing filtering operation before differentiation. This shows that this
      part of edge detection consists of two steps, a filtering step and a
      differentiation step. Following this perspective, the paper discusses in detail
      the following theoretical aspects of edge detection. 1) The properties of
      different types of filters-with minimal uncertainty, with a bandpass spectrum,
      and with limited support-are derived. Minimal uncertainty filters optimize a
      tradeoff between computational efficiency and regularizing properties. 2)
      Relationships among several 2-D differential operators are established. In
      particular, we characterize the relation between the Laplacian and the second
      directional derivative along the gradient. Zero crossings of the Laplacian are
      not the only features computed in early vision. 3) Geometrical and topological
      properties of the zero crossings of differential operators are studied in terms
      of transversality and Morse theory.

PMID- 21869335
TI  - Optimal edge detector design I: parameter selection and noise effects.
AB  - This paper comments on the optimality of the Laplacian of a Gaussian edge
      detection filter which localizes edges through zero crossings in the filtered
      image. The arguments of both Marr and Hildreth, and Dickey and Shanmugam are
      reviewed to establish that the filter is optimal in the sense of maximizing
      output image energy near edge features. This filter's principal advantage over
      other edge detectors is that its response is user-adjustable through selection of
      a single parameter, the Gaussian standard deviation. However, no clear method for
      the selection of this parameter has been provided. The problem is addressed here
      by applying the filter to two ideal periodic edge models blurred by a Gaussian
      distribution point-spread function. The observed response to the edge spacing and
      blur standard deviation is then translated into a filter parameter design
      procedure. The problems of optimum filter performance in the presence of additive
      Gaussian noise are then addressed. The problem of selecting the sampled filter's
      coefficient word size is dealt with in a companion paper.

PMID- 21869336
TI  - Optimal Edge Detector Design II: Coefficient Quantization.
AB  - A companion paper describes the design and implementation of the Laplacian of a
      Gaussian edge detection filter which localizes edges through zero crossings in
      the filtered image. Accuracy in the presence of noise has been found to be
      proportional to the square root of the filter's standard deviation. Digital
      implementation of any continuous filter requires sampling and coefficient
      quantization. The sampled filter was examined, but a method is proposed here for
      selection of a minimum coefficient word size for direct-form implementation to
      satisfy in-band rejection bounds.

PMID- 21869337
TI  - ANGY: A Rule-Based Expert System for Automatic Segmentation of Coronary Vessels
      From Digital Subtracted Angiograms.
AB  - This paper details the design and implementation of ANGY, a rule-based expert
      system in the domain of medical image processing. Given a subtracted digital
      angiogram of the chest, ANGY identifies and isolates the coronary vessels, while
      ignoring any nonvessel structures which may have arisen from noise, variations in
      background contrast, imperfect subtraction, and irrelevent anatomical detail. The
      overall system is modularized into three stages: the preprocessing stage and the
      two stages embodied in the expert itself. In the preprocessing stage, low-level
      image processing routines written in C are used to create a segmented
      representation of the input image. These routines are applied sequentially. The
      expert system is rule-based and is written in OPS5 and LISP. It is separated into
      two stages: The low-level image processing stage embodies a domain-independent
      knowledge of segmentation, grouping, and shape analysis. Working with both edges
      and regions, it determines such relations as parallel and adjacent and attempts
      to refine the segmentation begun by the preprocessing. The high-level medical
      stage embodies a domain-dependent knowledge of cardiac anatomy and physiology.
      Applying this knowledge to the objects and relations determined in the preceding
      two stages, it identifies those objects which are vessels and eliminates all
      others.

PMID- 21869338
TI  - Collision detection for moving polyhedra.
AB  - We consider the collision-detection problem for a three-dimensional solid object
      moving among polyhedral obstacles. The configuration space for this problem is
      six-dimensional, and the traditional representation of the space uses three
      translational parameters and three angles (typically Euler angles). The
      constraints between the object and obstacles then involve trigonometric
      functions. We show that a quaternion representation of rotation yields
      constraints which are purely algebraic in a seven-dimensional space. By simple
      manipulation, the constraints may be projected down into a six-dimensional space
      with no increase in complexity. The algebraic form of the constraints greatly
      simplifies computation of collision points, and allows us to derive an efficient
      exact intersection test for an object which is translating and rotating among
      obstacles.

PMID- 21869339
TI  - Mesh-Oriented Line Drawings Theory (MOLD Theory).
AB  - In this paper, we describe a new model of bilevel digital images of line
      drawings. The key idea is that the constraints of generating the line drawings
      are available to select patterns which are considered to be a certain local
      appearance of line drawings. Concretely, when a bilevel digital image of line
      drawings is observed by 3 * 3 pixels' unit mesh, the patterns occurring in the
      unit mesh are restricted by the constraints that the digital image is line
      structured. At first, lines in a digital image are strictly defined and then two
      assumptions related to the minimum line width and observing unit mesh are
      introduced. It is theoretically derived what kinds of patterns occur under these
      conditions and we call them ''legal patterns,'' while the other patterns not
      satisfying above conditions are called ''illegal patterns.'' Next, new
      representations such as SYM pictures and LSC pictures, which consist only of
      legal patterns, are proposed as a model of bilevel digital images of line
      drawings and the algorithms to transcribe the original bilevel digital image into
      the new representations in the model are introduced. Finally, the experimental
      results are evaluated from the viewpoint of the amount of data involved in the
      new representations. The results show that our theory is well-fitted to actual
      images and that many useful and practical applications will be derived not only
      in the field of documents processing, but also of digital communication.

PMID- 21869340
TI  - Digital image registration using projections.
AB  - In many application fields (e.g., aerospace and biomedical image processing), one
      has to deal with a sequence of images whose observation is made difficult by
      unpredictable relative movements of the camera and the scene. In order to obtain
      a stable display, the displacement of each image in the sequence with respect to
      one chosen as a reference must be preliminarily determined. This would usually
      require two-dimensional algorithms, involving a considerable computational
      effort. This work discusses a new algorithm for image registration, which
      requires only one-dimensional Fourier transformations. Preliminary experimental
      results are reported.

PMID- 21869341
TI  - Efficient synthesis of gaussian filters by cascaded uniform filters.
AB  - Gaussian filtering is an important tool in image processing and computer vision.
      In this paper we discuss the background of Gaussian filtering and look at some
      methods for implementing it. Consideration of the central limit theorem suggests
      using a cascade of ''simple'' filters as a means of computing Gaussian filters.
      Among ''simple'' filters, uniform-coefficient finite-impulse-response digital
      filters are especially economical to implement. The idea of cascaded uniform
      filters has been around for a while [13], [16]. We show that this method is
      economical to implement, has good filtering characteristics, and is appropriate
      for hardware implementation. We point out an equivalence to one of Burt's methods
      [1], [3] under certain circumstances. As an extension, we describe an approach to
      implementing a Gaussian Pyramid which requires approximately two addition
      operations per pixel, per level, per dimension. We examine tradeoffs in choosing
      an algorithm for Gaussian filtering, and finally discuss an implementation.

PMID- 21869342
TI  - A Test of the Gaussian-ness of a Data Set Using Clustering.
AB  - The properties of the ''magnifying glass'' method of clustering are discussed.
      These properties, which include unbiased and consistent estimation of the mean
      for Gaussian distributions and biased and inconsistent estimation of the mean for
      non-Gaussian distributions, lead to the development of a technique for testing
      data to determine whether or not it is Gaussian. An example of a non-Gaussian
      distribution is given to show the sensitivity of the proposed Gaussian test.

PMID- 21869343
TI  - Efficient Implementation of the Fuzzy c-Means Clustering Algorithms.
AB  - This paper reports the results of a numerical comparison of two versions of the
      fuzzy c-means (FCM) clustering algorithms. In particular, we propose and
      exemplify an approximate fuzzy c-means (AFCM) implementation based upon replacing
      the necessary ''exact'' variates in the FCM equation with integer-valued or real
      valued estimates. This approximation enables AFCM to exploit a lookup table
      approach for computing Euclidean distances and for exponentiation. The net effect
      of the proposed implementation is that CPU time during each iteration is reduced
      to approximately one sixth of the time required for a literal implementation of
      the algorithm, while apparently preserving the overall quality of terminal
      clusters produced. The two implementations are tested numerically on a nine-band
      digital image, and a pseudocode subroutine is given for the convenience of
      applications-oriented readers. Our results suggest that AFCM may be used to
      accelerate FCM processing whenever the feature space is comprised of tuples
      having a finite number of integer-valued coordinates.

PMID- 21869344
TI  - Relaxation labeling with learning automata.
AB  - Relaxation labeling processes are a class of mechanisms that solve the problem of
      assigning labels to objects in a manner that is consistent with respect to some
      domain-specific constraints. We reformulate this using the model of a team of
      learning automata interacting with an environment or a high-level critic that
      gives noisy responses as to the consistency of a tentative labeling selected by
      the automata. This results in an iterative linear algorithm that is itself
      probabilistic. Using an explicit definition of consistency we give a complete
      analysis of this probabilistic relaxation process using weak convergence results
      for stochastic algorithms. Our model can accommodate a range of uncertainties in
      the compatibility functions. We prove a local convergence result and show that
      the point of convergence depends both on the initial labeling and the
      constraints. The algorithm is implementable in a highly parallel fashion.

PMID- 21869345
TI  - Encoding of line drawings with a multiple grid chain code.
AB  - The multiple grid(MG) chain code which uses four different square grids is
      proposed to encode line drawings. The main processes adopted in the code are: 1)
      a grid selection algorithm which allocates quantization points only to the
      vicinity of the course of a line drawing, 2) labeling rule on quantization points
      which makes the frequency of some codes larger than that of other codes, and 3)
      quantization points allocation-not to the corners, but to the sides of a square
      which makes the straight line segments larger without increasing quantization
      error. A performance comparison of various chain codes is made from the
      viewpoints of the encoding efficiency, naturalness of the encoded lines, and the
      rate distortion measure. Also, the superiority of the MG chain code to other
      codes is shown. At last, application of the MG chain code to the electronic
      blackboard system is explained.

PMID- 21869346
TI  - Best linear unbiased estimators for properties of digitized straight lines.
AB  - This paper considers the problem of measuring properties of digitized straight
      lines from the viewpoint of measurement methodology. The measurement and
      estimation process is described in detail, revealing the importance of a step
      called ''characterization'' which was not recognized explicitly before. Using
      this new concept, BLUE (Best Linear Unbiased) estimators are found. These are
      calculated for various properties of digitized straight lines, and are briefly
      compared to previous work.

PMID- 21869347
TI  - One-dimensional scan selection for two-dimensional signal restoration.
AB  - The problem of m-D filtering using sequential scanning is considered. It is shown
      that the optimal causal filter and the performance measure depend on the scan
      selected. Examples show that this effect can be significant. Possible techniques
      to select a suitable scan are analyzed.

PMID- 21869348
TI  - On the local optimality of the fuzzy isodata clustering algorithm.
AB  - The convergence of the fuzzy ISODATA clustering algorithm was proved by Bezdek
      [3]. Two sets of conditions were derived and it was conjectured that they are
      necessary and sufficient for a local minimum point. In this paper, we address
      this conjecture and explore the properties of the underlying optimization
      problem. The notions of reduced objective function and improving and feasible
      directions are used to examine this conjecture. Finally, based on the derived
      properties of the problem, a new stopping criterion for the fuzzy ISODATA
      algorithm is proposed.

PMID- 21869349
TI  - An algorithm for learning without external supervision and its application to
      learning control systems.
AB  - An algorithm is proposed for the design of ''on-line'' learning controllers to
      control a discrete stochastic plant. The subjective probabilities of applying
      control actions from a finite set of allowable actions using random strategy,
      after any plant-environment situation (called an ''event'') is observed, are
      modified through the algorithm. The subjective probability for the optimal action
      is proved to approach one with probability one for any observed event. The
      optimized performance index is the conditional expectation of the instantaneous
      performance evaluations with respect to the observed events and the allowable
      actions. The algorithm is described through two transformations, T1, and T2.
      After the ''ordering transformation'' T1 is applied on the estimates of the
      performance indexes of the allowable actions, the ''learning transformation'' T2
      modifies the subjective probabilities. The cases of discrete and continuous
      features are considered. In the latter, the Potential Function Method is
      employed. The algorithm is compared with a linear reinforcement schenme and
      computer simulation results are presented.

PMID- 21869350
TI  - A dynamic programming approach to sequential pattern recognition.
AB  - This paper presents the dynamic programming approach to the design of optimal
      pattern recognition systems when the costs of feature measurements describing the
      pattern samples are of considerable importance. A multistage or sequential
      pattern classifier which requires, on the average, a substantially smaller number
      of feature measurements than that required by an equally reliable nonsequential
      classifier is defined and constructed through the method of recursive
      optimization. Two methods of reducing the dimensionality in computation are
      presented for the cases where the observed feature measurements are 1)
      statistically independent, and 2) Markov dependent. Both models, in general,
      provide a ready solution to the optimal sequential classification problem. A
      generalization in the design of optimal classifiers capable of selecting a best
      sequence of feature measurements is also discussed. Computer simulated
      experiments in character recognition are shown to illustrate the feasibility of
      this approach.

PMID- 21869351
TI  - Learning control systems-review and outlook.
AB  - The basic concept of learning control is introduced. The following five learning
      schemes are briefly reviewed: 1) trainable controllers using pattern classifiers,
      2) reinforcement learning control systems, 3) Bayesian estimation, 4) stochastic
      approximation, and 5) stochastic automata models. Potential applications and
      problems for further research in learning control are outlined.

PMID- 21869352
TI  - Grammatical inference: introduction and survey-part I.
AB  - The problem of grammatical inference is introduced, and its potential engineering
      applications are demonstrated. Inference algorithms for finite-state and context
      free grammars are presented. The application of some of the algorithms to the
      inference of pattern grammars in syntactic pattern recognition is illustrated by
      examples.

PMID- 21869353
TI  - Grammatical Inference: Introduction and Survey-Part II.
AB  - Inference of high-dimensional grammars is discussed. Specifically, techniques for
      inferring tree grammars are briefly presented. The problem of inferring a
      stochastic grammar to model the behavior of an information source is also
      introduced and techniques for carrying out the inference process are presented
      for a class of stochastic finite-state and context-free grammars. The possible
      practical application of these methods is illustrated by examples.

PMID- 21869354
TI  - A tree system approach for fingerprint pattern recognition.
AB  - The purpose of this paper is to demonstrate how a syntactic approach and, in
      particular, a tree system may be used to represent and classify fingerprint
      patterns. The fingerprint impressions are subdivided into sampling squares which
      are preprocessed and postprocessed for feature extraction. A set of regular tree
      languages is used to describe the fingerprint patterns and a set of tree automata
      is used to recognize the coded patterns. In order to infer the structural
      configuration of the encoded fingerprints, a grammatical inference system is
      developed. This sytem utilizes a simple procedure to infer the numerous
      substructures and relies on a reachability matrix and a man-machine interactive
      technique for the inference of complex structures. The 92 fingerprint impressions
      were used to test the proposed approach. A set of 193 tree grammars was inferred
      from each sampling square of the 4 * 4 sampling matrix which is capable of
      generating about 2 * 1034 classes for the fingerprint patterns.

PMID- 21869355
TI  - Shape discrimination using fourier descriptors.
AB  - Description or discrimination of boundary curves (shapes) is an important problem
      in picture processing and pattern recognition Fourier descriptors (FD's) have
      interesting properties in this respect. First, a critical review is given of two
      kinds of FD's. Some properties of the FD's are given and a distance measure is
      proposed, in terms of FD's, that measures the difference between two boundarv
      curves. It is shown how FD's can be used for obtaining skeletons fobjects.
      Finally, experimental results are given in character recognition and machine
      parts recognition.

PMID- 21869356
TI  - A step towards unification of syntactic and statistical pattern recognition.
AB  - The problem of pattern recognition is discussed in terms of single-entity
      representation versus multiple-entity representation. A combined syntactic
      semantic approach based on attributed grammars is suggested. Syntax-semantics
      tradeoff in pattern representation is demonstrated. This approach is intended to
      be an initial step toward unification of syntactic and statistical approaches to
      pattern recognition.

PMID- 21869357
TI  - An investigation of smoothness constraints for the estimation of displacement
      vector fields from image sequences.
AB  - A mapping between one frame from an image sequence and the preceding or following
      frame can be represented as a displacement vector field. In most situations, the
      mere gray value variations do not provide sufficient information in order to
      estimate such a displacement vector field. Supplementary constraints are
      necessary, for example the postulate that a displacement vector field varies
      smoothly as a function of the image position. Taken as a general requirement,
      this creates difficulties at gray value transitions which correspond to occluding
      contours. Nagel therefore introduced the ''oriented smoothness'' requirement
      which restricts variations of the displacement vector field only in directions
      with small or no variation of gray values. This contribution reports results of
      an investigation about how such an ''oriented smoothness'' constraint may be
      formulated and evaluated.

PMID- 21869358
TI  - A parallel algorithm for stochastic image segmentation.
AB  - A parallel algorithm for syntactic image segmentation is introduced. Stochastic
      tree grammar is used as a context-generating model. It is shown that when this
      context-generating process is in the equilibrium state, a matched filter can be
      designed and applied in parallel to the image. This process can be used for image
      segmentation in a syntactic pattern recognition system to enhance the performance
      of the succeeding recognition process.

PMID- 21869359
TI  - An image understanding system using attributed symbolic representation and
      inexact graph-matching.
AB  - This paper presents a powerful image understanding system that utilizes a
      semantic-syntactic (or attributed-synibolic) representation scheme in the form of
      attributed relational graphs (ARG's) for comprehending the global information
      contents of images. Nodes in the ARG represent the global image features, while
      the relations between those features are represented by attributed branches
      between their corresponding nodes. The extraction of ARG representation from
      images is achieved by a multilayer graph transducer scheme. This scheme is
      basically a rule-based system that uses a combination of model-driven and data
      driven concepts in performing a hierarchical symbolic mapping of the image
      information content from the spatial-domain representation into a global
      representation. Further analysis and inter-pretation of the imagery data is
      performed on the extracted ARG representation. A distance measure between images
      is defined in terms of the distance between their respective ARG representations.
      The distance between two ARG's and the inexact matching of their respective
      components are calculated by an efficient dynamic programming technique. The
      system handles noise, distortion, and ambiguity in real-world images by two
      means, namely, through modeling and embedding them into the transducer's mapping
      rules, as well as through the appropriate cost of error-transformation for the
      inexact matching of the ARG image representation. Two illustrative experiments
      are presented to demonstrate some capabilities of the proposed system. Experiment
      I deals with locating objects in multiobject scenes, while Experiment II is
      concerned with target detection in SAR images.

PMID- 21869360
TI  - On optimally combining pieces of information, with application to estimating 3-d
      complex-object position from range data.
AB  - New asymptotic methods are introduced that permit computationally simple Bayesian
      recognition and parameter estimation for many large data sets described by a
      combination of algebraic, geometric, and probabilistic models. The techniques
      introduced permit controlled decomposition of a large problem into small problems
      for separate parallel processing where maximum likelihood estimation or Bayesian
      estimation or recognition can be realized locally. These results can be combined
      to arrive at globally optimum estimation or recognition. The approach is applied
      to the maximum likelihood estimation of 3-D complex-object position. To this end,
      the surface of an object is modeled as a collection of patches of primitive
      quadrics, i.e., planar, cylindrical, and spherical patches, possibly augmented by
      boundary segments. The primitive surface-patch models are specified by geometric
      parameters, reflecting location, orientation, and dimension information. The
      object-position estimation is based on sets of range data points, each set
      associated with an object primitive. Probability density functions are introduced
      that model the generation of range measurement points. This entails the
      formulation of a noise mechanism in three-space accounting for inaccuracies in
      the 3-D measurements and possibly for inaccuracies in the 3-D modeling. We
      develop the necessary techniques for optimal local parameter estimation and
      primitive boundary or surface type recognition for each small patch of data, and
      then optimal combining of these inaccurate locally derived parameter estimates in
      order to arrive at roughly globally optimum object-position estimation.

PMID- 21869361
TI  - A pyramid-based approach to segmentation applied to region matching.
AB  - In this paper, we attempt to place segmentation schemes utilizing the pyramid
      architecture on a firm footing. We show that there are some images which cannot
      be segmented in principle. An efficient segmentation scheme is also developed
      using pyramid relinking. This scheme will normally have a time complexity which
      is a sublinear function of the image diameter, which compares favorably to other
      schemes. The efficacy of our approach to segmentation using pyramid schemes is
      demonstrated in the context of region matching. The global features we use are
      compared to those used in previous approaches and this comparison will indicate
      that our approach is more robust than the standard moment-based techniques.

PMID- 21869362
TI  - Detection of intensity changes with subpixel accuracy using laplacian-gaussian
      masks.
AB  - We present a system that takes a gray level image as input, locates edges with
      subpixel accuracy, and links them into lines. Edges are detected by finding zero
      crossings in the convolution of the image with Laplacian-of-Gaussian (LoG) masks.
      The implementation differs markedly from M.I.T.'s as we decompose our masks
      exactly into a sum of two separable filters instead of the usual approximation by
      a difference of two Gaussians (DOG). Subpixel accuracy is obtained through the
      use of the facet model [1]. We also note that the zero-crossings obtained from
      the full resolution image using a space constant ? for the Gaussian, and those
      obtained from the 1/n resolution image with 1/n pixel accuracy and a space
      constant of ?/n for the Gaussian, are very similar, but the processing times are
      very different. Finally, these edges are grouped into lines using the technique
      described in [2].

PMID- 21869363
TI  - Filtering closed curves.
AB  - A closed curve in the plane can be described in several ways. We show that a
      simple representation in terms of radius of curvature versus normal direction has
      certain advantages. In particular, convolutional filtering of the extended
      circular image leads to a closed curve. Similar filtering operations applied to
      some other representations of the curve do not guarantee that the result
      corresponds to a closed curve. In one case, where a closed curve is produced, it
      is smaller than the original. A description of a curve can be based on a sequence
      of smoothed versions of the curve. This is one reason why smoothing of closed
      curves is of interest.

PMID- 21869364
TI  - Contribution to the prediction of performances of the hough transform.
AB  - Exact predictions of the performances of the Hough detection of straight lines in
      two-dimensional images are presented for rectangular and circular retinas, in
      Cartesian and normal parameterization, in the case of noisy signals. Detection of
      circles, under the same assumptions, is discussed. The limits of adaptive
      quantization to reduce intrinsic noise are presented, and it is shown that a
      signal processing approach is especially convenient to measure the performances
      of a detector based on the Hough transform.

PMID- 21869365
TI  - A computational approach to edge detection.
AB  - This paper describes a computational approach to edge detection. The success of
      the approach depends on the definition of a comprehensive set of goals for the
      computation of edge points. These goals must be precise enough to delimit the
      desired behavior of the detector while making minimal assumptions about the form
      of the solution. We define detection and localization criteria for a class of
      edges, and present mathematical forms for these criteria as functionals on the
      operator impulse response. A third criterion is then added to ensure that the
      detector has only one response to a single edge. We use the criteria in numerical
      optimization to derive detectors for several common image features, including
      step edges. On specializing the analysis to step edges, we find that there is a
      natural uncertainty principle between detection and localization performance,
      which are the two main goals. With this principle we derive a single operator
      shape which is optimal at any scale. The optimal detector has a simple
      approximate implementation in which edges are marked at maxima in gradient
      magnitude of a Gaussian-smoothed image. We extend this simple detector using
      operators of several widths to cope with different signal-to-noise ratios in the
      image. We present a general method, called feature synthesis, for the fine-to
      coarse integration of information from operators at different scales. Finally we
      show that step edge detector performance improves considerably as the operator
      point spread function is extended along the edge.

PMID- 21869366
TI  - On detecting edges.
AB  - An edge in an image corresponds to a discontinuity in the intensity surface of
      the underlying scene. It can be approximated by a piecewise straight curve
      composed of edgels, i.e., short, linear edgeelements, each characterized by a
      direction and a position. The approach to edgel-detection here, is to fit a
      series of one-dimensional surfaces to each window (kernel of the operator) and
      accept the surfacedescription which is adequate in the least squares sense and
      has the fewest parameters. (A one-dimensional surface is one which is constant
      along some direction.) The tanh is an adequate basis for the step-edge and its
      combinations are adequate for the roof-edge and the line-edge. The proposed
      method of step-edgel detection is robust with respect to noise; for (step
      size/noise) > 2.5, it has subpixel position localization (position < 3) and an
      angular localization better than 100; further, it is designed to be insensitive
      to smooth shading. These results are demonstrated by some simple analysis,
      statistical data, and edgel-images. Also included is a comparison of performance
      on a real image, with a typical operator (Difference-of-Gaussians). The results
      indicate that the proposed operator is superior with respect to detection,
      localization, and resolution.

PMID- 21869367
TI  - Binocular image flows: steps toward stereo-motion fusion.
AB  - The analyses of visual data by stereo and motion modules have typically been
      treated as separate parallel processes which both feed a common viewer-centered
      2.5-D sketch of the scene. When acting separately, stereo and motion analyses are
      subject to certain inherent difficulties; stereo must resolve a combinatorial
      correspondence problem and is further complicated by the presence of occluding
      boundaries, motion analysis involves the solution of nonlinear equations and
      yields a 3-D interpretation specified up to an undetermined scale factor. A new
      module is described here which unifies stereo and motion analysis in a manner in
      which each helps to overcome the other's short-comings. One important result is a
      correlation between relative image flow (i.e., binocular difference flow) and
      stereo disparity; it points to the importance of the ratio ? ?, rate of change of
      disparity ? to disparity ?, and its possible role in establishing stereo
      correspondence. The importance of such ratios was first pointed out by Richards
      [19]. Our formulation may reflect the human perception channel probed by Regan
      and Beverley [18].

PMID- 21869368
TI  - One-eyed stereo: a general approach to modeling 3-d scene geometry.
AB  - A single two-dimensional image is an ambiguous representation of the three
      dimensional world?many different scenes could have produced the same image?yet
      the human visual system is ex-tremely successful at recovering a qualitatively
      correct depth model from this type of representation. Workers in the field of
      computational vision have devised a number of distinct schemes that attempt to
      emulate this human capability; these schemes are collectively known as ''shape
      from...'' methods (e.g., shape from shading, shape from texture, or shape from
      contour). In this paper we contend that the distinct assumptions made in each of
      these schemes is tantamount to providing a second (virtual) image of the original
      scene, and that each of these approaches can be translated into a conventional
      stereo formalism. In particular, we show that it is frequently possible to
      structure the problem as one of recovering depth from a stereo pair consisting of
      the supplied perspective image (the original image) and an hypothesized
      orthographic image (the virtual image). We present a new algorithm of the form
      required to accomplish this type of stereo reconstruction task.

PMID- 21869369
TI  - Natural Language Modeling for Phoneme-to-Text Transcription.
AB  - This paper relates different kinds of language modeling methods that can be
      applied to the linguistic decoding part of a speech recognition system with a
      very large vocabulary. These models are studied experimentally on a
      pseudophonetic input arising from French stenotypy. We propose a model which
      combines the advantages of a statistical modeling with information theoretic
      tools, and those of a grammatical approach.

PMID- 21869370
TI  - Determining object translation information using stereoscopic motion.
AB  - Stereoscopic motion is an approach for comparing image change due to motion in a
      stereo pair of image sequences. Qualitatively, the relative image change shows
      that an object point is approaching, receding, or remaining at constant depth.
      Quantitatively, the relative change predicts where the object point will pass
      with respect to the camera system.

PMID- 21869371
TI  - A method for the analysis of ambiguous segmentations of images.
AB  - In this correspondence we are interested in how interpretation and context
      restrictions can guide the analysis of ambiguous segmentations of images in
      computer vision systems. The final objective is to find image segments that can
      be interpreted (classified) such that their interpretations do not conflict with
      interpretations given to related segments. In the case that we have several
      possible labels for each segment, some of this ambiguity can be reduced by means
      of a relaxation process. In its discrete formulation, the relaxation operator
      examines pairs of related segments to see if they have incompatible labels, which
      are then discarded. This process is iterated until only compatible labels are
      left. In this work a new approach is proposed that considers all possible
      segmentations resulting from an ambiguous segmentation simultaneously in only one
      relaxation process. A new relaxation operator is defined that can be applied to
      ambiguous segmentations. In this way no backtracking is performed, ambiguity is
      reduced, and the best solution is still retained. The output of the process is a
      collection of segmentations and interpretations that is hopefully small enough so
      that each case can be considered separately.

PMID- 21869372
TI  - A Fast k Nearest Neighbor Finding Algorithm Based on the Ordered Partition.
AB  - We propose a fast nearest neighbor finding algorithm, named tentatively an
      ordered partition, based on the ordered lists of the training samples of each
      projection axis. The ordered partition contains two properties, one is
      ordering?to bound the search region, and the other is partitioning?to reject the
      unwanted samples without actual distance computations. It is proved that the
      proposed algorithm can find k nearest neighbors in a constant expected time.
      Simulations show that the algorithm is rather distribution free, and only 4.6
      distance calculations, on the average, were required to find a nearest neighbor
      among 10 000 samples drawn from a bivariate normal distribution.

PMID- 21869373
TI  - The synthesis and analysis of color images.
AB  - I describe a method for performing the synthesis and analysis of digital color
      images. The method is based on two principles. First, image data are represented
      with respect to the separate physical factors, surface reflectance and the
      spectral power distribution of the ambient light, that give rise to the perceived
      color of an object. Second, the encoding is made efficient by using a basis
      expansion for the surface spectral reflectance and spectral power distribution of
      the ambient light that takes advantage of the high degree of correlation across
      the visible wavelengths normally found in such functions. Within this framework,
      the same basic methods can be used to synthesize image data for color display
      monitors and printed materials, and to analyze image data into estimates of the
      spectral power distribution and surface spectral reflectances. The method can be
      applied to a variety of tasks. Examples of applications include the color
      balancing of color images and the identification of material surface spectral
      reflectance when the lighting cannot be completely controlled.

PMID- 21869374
TI  - Color-encoded structured light for rapid active ranging.
AB  - In this paper, we discuss a novel strategy for rapid acquisition of the range map
      of a scene employing color-encoded structured light. This technique offers
      several potential advantages including increased speed and improved accuracy. In
      this approach we illuminate the scene with a single encoded grid of colored light
      stripes. The indexing problem, that of matching a detected image plane stripe
      with its position in the projection grid, is solved from a knowledge of the color
      grid encoding. In fact, the possibility exists for the first time to acquire high
      resolution range data in real time for modest cost, since only a single
      projection and single color image are required. Grid to grid alignment problems
      associated with previous multistripe techniques are eliminated, as is the
      requirement for dark interstices between grid stripes. Scene illumination is more
      uniform, simplifying the stripe detection problem, and mechanical difficulties
      associated with the equipment design are significantly reduced.

PMID- 21869375
TI  - Toward a Fundamental Theory of Optimal Feature Selection: Part II-Implementation
      and Computational Complexit.
AB  - Certain algorithms and their computational complexity are examined for use in a
      VLSI implementation of the real-time pattern classifier described in Part I of
      this work. The most computationally intensive processing is found in the
      classifier training mode wherein subsets of the largest and smallest eigenvalues
      and associated eigenvectors of the input data covariance pair must be computed.
      It is shown that if the matrix of interest is centrosymmetric and the method for
      eigensystem decomposition is operator-based, the problem architecture assumes a
      parallel form. Such a matrix structure is found in a wide variety of pattern
      recognition and speech and signal processing applications. Each of the parallel
      channels requires only two specialized matrix-arithmetic modules. These modules
      may be implemented as linear arrays of processing elements having at most O(N)
      elements where N is the input data vector dimension. The computations may be done
      in O(N) time steps. This compares favorably to O(N3) operations for a
      conventional, or general, rotation-based eigensystem solver and even the O(2N2)
      operations using an approach incorporating the fast Levinson algorithm for a
      matrix of Toeplitz structure since the underlying matrix in this work does not
      possess a Toeplitz structure. Some examples are provided on the convergence of a
      conventional iterative approach and a novel two-stage iterative method for
      eigensystem decomposition.

PMID- 21869376
TI  - Modeling and segmentation of noisy and textured images using gibbs random fields.
AB  - This paper presents a new approach to the use of Gibbs distributions (GD) for
      modeling and segmentation of noisy and textured images. Specifically, the paper
      presents random field models for noisy and textured image data based upon a
      hierarchy of GD. It then presents dynamic programming based segmentation
      algorithms for noisy and textured images, considering a statistical maximum a
      posteriori (MAP) criterion. Due to computational concerns, however, sub-optimal
      versions of the algorithms are devised through simplifying approximations in the
      model. Since model parameters are needed for the segmentation algorithms, a new
      parameter estimation technique is developed for estimating the parameters in a
      GD. Finally, a number of examples are presented which show the usefulness of the
      Gibbsian model and the effectiveness of the segmentation algorithms and the
      parameter estimation procedures.

PMID- 21869377
TI  - Finding trajectories of feature points in a monocular image sequence.
AB  - Identifying the same physical point in more than one image, the correspondence
      problem, is vital in motion analysis. Most research for establishing
      correspondence uses only two frames of a sequence to solve this problem. By using
      a sequence of frames, it is possible to exploit the fact that due to inertia the
      motion of an object cannot change instantaneously. By using smoothness of motion,
      it is possible to solve the correspondence problem for arbitrary motion of
      several nonrigid objects in a scene. We formulate the correspondence problem as
      an optimization problem and propose an iterative algorithm to find trajectories
      of points in a monocular image sequence. A modified form of this algorithm is
      useful in case of occlusion also. We demonstrate the efficacy of this approach
      considering synthetic, laboratory, and real scenes.

PMID- 21869378
TI  - A new class of detail-preserving filters for image processing.
AB  - A new class of median type filters for image processing is proposed. In the
      filters, linear FIR substructures are used in conjunction with the median
      operation. The root signals and noise attenuation properties of the FIR-median
      hybrid filters are analyzed and compared to representative edge preserving
      filtering operations. The concept of multilevel median operation is introduced to
      improve the detail preserving property of conventional median and the FIR-median
      hybrid filters. In the multilevel filters there exists a tradeoff between noise
      attenuation and detail preservation. The analysis and examples indicate that FIR
      median hybrid filters preserve details better and are computationally much more
      efficient than the conventional median and the K-nearest neighbor averaging
      filters.

PMID- 21869379
TI  - Large tree classifier with heuristic search and global training.
AB  - In the tree classifier with top-down search, a global decision is made via a
      series of local decisions. Although this approach gains in classification
      efficiency, it also gives rise to error accumulation which can be very harmful
      when the number of classes is very large. To overcome this difficulty, a new tree
      classifier with the following characteristics is proposed: 1) fuzzy logic search
      is used to find all ''possible correct classes,'' and some similarity measures
      are used to determine the ''most probable class''; 2) global training is applied
      to generate extended terminals in order to enhance the recognition rate; 3) both
      the training and search algorithms have been given a lot of flexibility, to
      provide tradeoffs between error and rejection rates, and between the recognition
      rate and speed. A computer simulation of the decision trees for the recognition
      of 3200 Chinese character categories yielded a very high recognition rate of
      99.93 percent and a very high speed of 861 samples/s, when the program was
      written in a high level language and run on a large multiuser time-sharing
      computer.

PMID- 21869380
TI  - Bias of nearest neighbor error estimates.
AB  - The bias of the finite-sample nearest neighbor (NN) error from its asymptotic
      value is examined. Expressions are obtained which relate the bias of the NN and 2
      NN errors to sample size, dimensionality, metric, and distributions. These
      expressions isolate the effect of sample size from that of the distributions,
      giving an explicit relation showing how the bias changes as the sample size is
      increased. Experimental results are given which suggest that the expressions
      accurately predict the bias. It is shown that when the dimensionality of the data
      is high, it may not be possible to estimate the asymptotic error simply by
      increasing the sample size. A new procedure is suggested to alleviate this
      problem. This procedure involves measuring the mean NN errors at several sample
      sizes and using our derived relationship between the bias and the sample size to
      extrapolate an estimate of the asymptotic NN error. The results are extended to
      the multiclass problem. The choice of an optimal metric to minimize the bias is
      also discussed.

PMID- 21869381
TI  - Multiple resolution representation and probabilistic matching of 2-d gray-scale
      shape.
AB  - One approach to pattern classification is to match a structural description of a
      pattern to models which describe the structural properties of pattern classes.
      The central problem in structural pattern matching is to determine the
      correspondence between the symbols which comprise a model and symbols which
      describe a pattern. The difficulty of determining this correspondence depends
      critically on the representation that is used to describe patterns. This
      correspondence presents a probabilistic representation for structural models of
      pattern classes. Both pattern descriptions and models for pattern classes are
      based on symbols which represent grayscale information at multiple resolutions. A
      pattern description is given by a tree of symbols with attribute values.
      Structural models are represented by a tree of symbols with probabilistic
      attributes. The position and scale (resolution) of the symbols, as well as other
      ''features,'' are represented by these attributes. An algorithm is presented for
      determining the correspondence between symbols in a description of a pattern and
      symbols in a model of a pattern class. This algorithm uses the connectivity
      between symbols at different scales to constrain the search for correspondence.
      An interactive training program for learning models of pattern classes is
      described, and some conclusions from the work are presented.

PMID- 21869382
TI  - Histogram analysis using a scale-space approach.
AB  - A new application of scale-space filtering to the classical problem of estimating
      the parameters of a normal mixture distribution is described. The technique
      involves generating a multiscale description of a histogram by convolving it with
      a series of Gaussians of gradually increasing width (standard deviation), and
      marking the location and direction of the sign change of zero-crossings in the
      second derivative. The resulting description, or fingerprint, is interpreted by
      relating pairs of zero-crossings to modes in the histogram where each mode or
      component is modeled by a normal distribution. Zero-crossings provide information
      from which estimates of the mixture parameters are computed. These initial
      estimates are subsequently refined using an iterative maximum likelihood
      estimation technique. Varying the scale or resolution of the analysis allows the
      number of components used in approximating the histogram to be controlled.

PMID- 21869383
TI  - Computation of surface orientation and structure of objects using grid coding.
AB  - In this correspondence, algorithms are introduced to infer surface orientation
      and structure of visible object surfaces using grid coding. We adopt the active
      lighting technique to spatially ''encode'' the scene for analysis. The observed
      objects, which can have surfaces of arbitrary shape, are assumed to rest on a
      plane (base plane) in a scene which is ''encoded'' with light cast through a grid
      plane. Two orthogonal grid patterns are used, where each pattern is obtained with
      a set of equally spaced stripes marked on a glass pane. The scene is observed
      through a camera and the object surface orientation is determined using the
      projected patterns on the object surface. If the surfaces under consideration
      obey certain smoothness constraints, a dense orientation map can be obtained
      through proper interpolation. The surface structure can then be recovered given
      this dense orientation map. Both planar and curved surfaces can be handled in a
      uniform manner. The algorithms we propose yield reasonably accurate results and
      are relatively tolerant to noise, especially when compared to shape-from-shading
      techniques. In contrast to other grid coding techniques reported which match the
      grid junctions for depth reconstruction under the stereopsis principle, our
      techniques use the direction of the projected stripes to infer local surface
      orientation and do not require any correspondence relationship between either the
      grid lines or the grid junctions to be specified. The algorithm has the ability
      to register images and can therefore be embedded in a system which integrates
      knowledge from multiple views.

PMID- 21869384
TI  - Gradient-type algorithms for partial singular value decomposition.
AB  - It is often desirable to calculate only a few terms of the SVD expansion of a
      matrix, corresponding to the largest or smallest singular values. Two algorithms,
      based on gradient and conjugate gradient search, are proposed for this purpose.
      SVD is computed term by term in a decreasing or increasing order of singular
      values. The algorithms are simple to implement and are especially advantageous
      with large matrices.

PMID- 21869385
TI  - Estimating Components of Univariate Gaussian Mixtures Using Prony's Method.
AB  - A new technique for estimating the component parameters of a mixture of
      univariate Gaussian distributions using the method of moments is presented. The
      method of moments basically involves equating the sample moments to the
      corresponding mixture moments expressed in terms of component parameters and
      solving these equations for the unknown parameters. These moment equations,
      however, are nonlinear in the unknown parameters, and heretofore, an analytic
      solution of these equations has been obtained only for two-component mixtures
      [2]. Numerical solutions also tend to be unreliable for more than two components,
      due to the large number of nonlinear equations and parameters to be solved for.
      In this correspondence, under the condition that the component distributions have
      equal variances or equal means, the nonlinear moment equations are transformed
      into a set of linear equations using Prony's method. The solution of these
      equations for the unknown parameters is analytically feasible and numerically
      reliable for mixtures with several components. Numerous examples using the
      proposed technique for two-, three-, and four-component mixtures are presented.

PMID- 21869386
TI  - Modified quadratic discriminant functions and the application to chinese
      character recognition.
AB  - Issues in the quadratic discriminant functions (QDF) are discussed and two types
      of modified quadratic disriminant functions (MQDF1, MQDF2) which are less
      sensitive to the estimation error of the covariance matrices are proposed. The
      MQDF1 is a function which employs a kind of a (pseudo) Bayesian estimate of the
      covariance matrix instead of the maximum likelihood estimate ordinarily used in
      the QDF. The MQDF2 is a variation of the MQDF1 to save the required computation
      time and storage. Two discriminant functions were applied to Chinese character
      recognition to evaluate their effectiveness, and remarkable improvement was
      observed in their performance.

PMID- 21869387
TI  - Semantic network array processor and its applications to image understanding.
AB  - The problems in computer vision range from edge detection and segmentation at the
      lowest level to the problem of cognition at the highest level. This
      correspondence describes the organization and operation of a semantic network
      array processor (SNAP) as applicable to high level computer vision problems. The
      architecture consists of an array of identical cells each containing a content
      addressable memory, microprogram control, and a communication unit. The
      applications discussed in this correspondence are the two general techniques,
      discrete relaxation and dynamic programming. While the discrete relaxation is
      discussed with reference to scene labeling and edge interpretation, the dynamic
      programming is tuned for stereo.

PMID- 21869388
TI  - Projection-based geometrical feature extraction for computer vision: algorithms
      in pipeline architectures.
AB  - In this correspondence, some image transforms and features such as projections
      along linear patterns, convex hull approximations, Hough transform for line
      detection, diameter, moments, and principal components will be considered.
      Specifically, we present algorithms for computing these features which are
      suitable for implementation in image analysis pipeline architectures. In
      particular, random access memories and other dedicated hardware components which
      may be found in the implementation of classical techniques are not longer needed
      in our algorithms. The effectiveness of our approach is demonstrated by running
      some of the new algorithms in conventional short-pipelines for image analysis. In
      related papers, we have shown a pipeline architecture organization called PPPE
      (Parallel Pipeline Projection Engine), which unleashes the power of projection
      based computer vision, image processing, and computer graphics. In the present
      correspondence, we deal with just a few of the many algorithms which can be
      supported in PPPE. These algorithms illustrate the use of the Radon transform as
      a tool for image analysis.

PMID- 21869389
TI  - Direct passive navigation.
AB  - In this correspondence, we show how to recover the motion of an observer relative
      to a planar surface from image brightness derivatives. We do not compute the
      optical flow as an intermediate step, only the spatial and temporal brightness
      gradients (at a minimum of eight points). We first present two iterative schemes
      for solving nine nonlinear equations in terms of the motion and surface
      parameters that are derived from a least-squares fomulation. An initial pass over
      the relevant image region is used to accumulate a number of moments of the image
      brightness derivatives. All of the quantities used in the iteration are
      efficiently computed from these totals without the need to refer back to the
      image. We then show that either of two possible solutions can be obtained in
      closed form. We first solve a linear matrix equation for the elements of a 3 * 3
      matrix. The eigenvalue decomposition of the symmetric part of the matrix is then
      used to compute the motion parameters and the plane orientation. A new compact
      notation allows us to show easily that there are at most two planar solutions.

PMID- 21869390
TI  - The effect of median filtering on edge estimation and detection.
AB  - In this paper we consider the effect of median prefiltering on the subsequent
      estimation and detection of edges in digital images. Where possible, a
      quantitative statistical comparison is made for a number of filters defined with
      two-dimensional geometries; in some cases one-dimensional analyses are required
      to illustrate certain points. Noise images prefiltered by median filters defined
      with a variety of windowing geometries are used to support the analysis, and it
      is found that median prefiltering improves the performance of both thresholding
      and zero-crossing based edge detectors.

PMID- 21869391
TI  - Simple parallel hierarchical and relaxation algorithms for segmenting noncausal
      markovian random fields.
AB  - The modeling and segmentation of images by MRF's (Markov random fields) is
      treated. These are two-dimensional noncausal Markovian stochastic processes. Two
      conceptually new algorithms are presented for segmenting textured images into
      regions in each of which the data are modeled as one of C MRF's. The algorithms
      are designed to operate in real time when implemented on new parallel computer
      architectures that can be built with present technology. A doubly stochastic
      representation is used in image modeling. Here, a Gaussian MRF is used to model
      textures in visible light and infrared images, and an autobinary (or autoternary,
      etc.) MRF to model a priori information about the local geometry of textured
      image regions. For image segmentation, the true texture class regions are treated
      either as a priori completely unknown or as a realization of a binary (or
      ternary, etc.) MRF. In the former case, image segmentation is realized as true
      maximum likelihood estimation. In the latter case, it is realized as true maximum
      a posteriori likelihood segmentation. In addition to providing a mathematically
      correct means for introducing geometric structure, the autobinary (or ternary,
      etc.) MRF can be used in a generative mode to generate image geometries and
      artificial images, and such simulations constitute a very powerful tool for
      studying the effects of these models and the appropriate choice of model
      parameters. The first segmentation algorithm is hierarchical and uses a pyramid
      like structure in new ways that exploit the mutual dependencies among disjoint
      pieces of a textured region.

PMID- 21869392
TI  - Scene segmentation from visual motion using global optimization.
AB  - This paper presents results from computer experiments with an algorithm to
      perform scene disposition and motion segmentation from visual motion or optic
      flow. The maximum a posteriori (MAP) criterion is used to formulate what the best
      segmentation or interpretation of the scene should be, where the scene is assumed
      to be made up of some fixed number of moving planar surface patches. The Bayesian
      approach requires, first, specification of prior expectations for the optic flow
      field, which here is modeled as spatial and temporal Markov random fields; and,
      secondly, a way of measuring how well the segmentation predicts the measured flow
      field. The Markov random fields incorporate the physical constraints that objects
      and their images are probably spatially continuous, and that their images are
      likely to move quite smoothly across the image plane. To compute the flow
      predicted by the segmentation, a recent method for reconstructing the motion and
      orientation of planar surface facets is used. The search for the globally optimal
      segmentation is performed using simulated annealing.

PMID- 21869393
TI  - Optical flow estimation: an error analysis of gradient-based methods with local
      optimization.
AB  - Multiple views of a scene can provide important information about the structure
      and dynamic behavior of three-dimensional objects. Many of the methods that
      recover this information require the determination of optical flow-the velocity,
      on the image, of visible points on object surfaces. An important class of
      techniques for estimating optical flow depend on the relationship between the
      gradients of image brightness. While gradient-based methods have been widely
      studied, little attention has been paid to accuracy and reliability of the
      approach. Gradient-based methods are sensitive to conditions commonly encountered
      in real imagery. Highly textured surfaces, large areas of constant brightness,
      motion boundaries, and depth discontinuities can all be troublesome for gradient
      based methods. Fortunately, these problematic areas are usually localized can be
      identified in the image. In this paper we examine the sources of errors for
      gradient-based techniques that locally solve for optical flow. These methods
      assume that optical flow is constant in a small neighborhood. The consequence of
      violating in this assumption is examined. The causes of measurement errors and
      the determinants of the conditioning of the solution system are also considered.
      By understanding how errors arise, we are able to define the inherent limitations
      of the technique, obtain estimates of the accuracy of computed values, enhance
      the performance of the technique, and demonstrate the informative value of some
      types of error.

PMID- 21869394
TI  - Image estimation using doubly stochastic gaussian random field models.
AB  - The two-dimensional (2-D) doubly stochastic Gaussian (DSG) model was introduced
      by one of the authors to provide a complete model for spatial filters which adapt
      to the local structure in an image signal. Here we present the optimal estimator
      and 2-D fixed-lag smoother for this DSG model extending earlier work of Ackerson
      and Fu. As the optimal estimator has an exponentially growing state space, we
      investigate suboptimal estimators using both a tree and a decision-directed
      method. Experimental results are presented.

PMID- 21869395
TI  - The nearest neighbor and the bayes error rates.
AB  - The (k, l) nearest neighbor method of pattern classification is compared to the
      Bayes method. If the two acceptance rates are equal then the asymptotic error
      rates satisfy the inequalities Ek,l + 1 ? E*(?) ? Ek,l dE*(?), where d is a
      function of k, l, and the number of pattern classes, and ? is the reject
      threshold for the Bayes method. An explicit expression for d is given which is
      optimal in the sense that for some probability distributions Ek,l and dE* (?) are
      equal.

PMID- 21869396
TI  - Structuring free space as a hypergraph for roving robot path planning and
      navigation.
AB  - This paper presents a method of structuring the free space of a roving robot's
      environment into a set of overlapping convex regions ideally suited to path
      planning and navigation tasks. The structure of the free space environment is
      maintained as a hypergraph with each convex region represented by a hyperedge
      identifying the boundary walls of the region. A new methodology reveals the
      structure of free space and constructs the hypergraph representation through a
      directed search for a set of fundamental circits in an abstract graphical
      representation of the environment geometry.

PMID- 21869397
TI  - On the recognition of printed characters of any font and size.
AB  - We describe the current state of a system that recognizes printed text of various
      fonts and sizes for the Roman alphabet. The system combines several techniques in
      order to improve the overall recognition rate. Thinning and shape extraction are
      performed directly on a graph of the run-length encoding of a binary image. The
      resulting strokes and other shapes are mapped, using a shape-clustering approach,
      into binary features which are then fed into a statistical Bayesian classifier.
      Large-scale trials have shown better than 97 percent top choice correct
      performance on mixtures of six dissimilar fonts, and over 99 percent on most
      single fonts, over a range of point sizes. Certain remaining confusion classes
      are disambiguated through contour analysis, and characters suspected of being
      merged are broken and reclassified. Finally, layout and linguistic context are
      applied. The results are illustrated by sample pages.

PMID- 21869398
TI  - Learning and plan refinement in a knowledge-based system for automatic speech
      recognition.
AB  - This paper shows how a semiautomatic design of a speech recognition system can be
      done as a planning activity. Recognition performances are used for deciding plan
      refinement. Inductive learning is performed for setting action preconditions.
      Experimental results in the recognition of connected letters spoken by 100
      speakers are presented.

PMID- 21869399
TI  - A rule-based system for verifying engineering specifications in industrial visual
      inspection applications.
AB  - An important step in automatic visual inspection is verifying whether a part is
      good or bad, by comparing a list of inspection specifications to a list of
      extracted and measured defects. Our goal is to provide a general, flexible, and
      efficient solution to this problem. We present a solution following a rule-based
      approach for the case of specs for visual inspection of disk heads. However, due
      to the generality of our approach (within the realm of visual inspection), it is
      easily extendible to verification of specs in other visual inspection
      applications. While flexibility comes naturally with the rule-based approach,
      efficiency is still an issue. Therefore, we implemented two techniques to
      increase the efficiency of our system: one at the rule level, and one at the rule
      matching level. We describe our implementation and show experimental results from
      applying our approach in an experimental system for automatic visual disk head
      inspection.

PMID- 21869400
TI  - A convex hull inclusion test.
AB  - A new characterization of the interior of the convex hull of a finite point set
      is given. An inclusion test based on this characterization is, on average, almost
      linear in the number of points times the dimensionality.

PMID- 21869401
TI  - Digital parallelism, perpendicularity, and rectangles.
AB  - The slope of digital line segments is defined and an algorithm to evaluate it is
      presented. Parallelism and perpendicularity of two digital line segments are also
      defined. Finally, rectangular digital regions are defined and characterized, and
      an algorithm that determines whether or not a given digital region is a digital
      rectangle is presented.

PMID- 21869402
TI  - On Extensions to Fisher's Linear Discriminant Function.
AB  - This correspondence describes extensions to Fisher's linear discriminant function
      which allow both differences in class means and covariances to be systematically
      included in a process for feature reduction. It is shown how the Fukunaga-Koontz
      transform can be combined with Fisher's method to allow a reduction of feature
      space from many dimensions to two. Performance is seen to be superior in general
      to the Foley-Sammon method. The technique is developed to show how a new radius
      vector (or pair of radius vectors) can be combined with Fisher's vector to
      produce a classifier with even more power of discrimination. Illustrations of the
      technique show that good discrimination can be obtained even if there is
      considerable overlap of classes in any one projection.

PMID- 21869403
TI  - Mobile robot localization using sonar.
AB  - This correspondence describes a method by which range data from a sonar
      rangefinder can be used to determine the two-dimensional position and orientation
      of a mobile robot inside a room. The plan of the room is modeled as a list of
      segments indicating the positions of walls. The algorithm works by correlating
      straight segments in the range data against the room model, then eliminating
      implausible configurations using the sonar barrier test, which exploits physical
      constraints on sonar data. The approach is extremely tolerant of noise and
      clutter. Transient objects such as furniture and people need not be included in
      the room model, and very noisy, low-resolution sensors can be used. The
      algorithm's performance is demonstrated using a Polaroid Ultrasonic Rangefinder.

PMID- 21869404
TI  - A Motion Stereo Method Based on Coarse-to-Fine Control Strategy.
AB  - This correspondence presents a motion stereo method based on coarse-to-fine
      control strategy. A camera sliding straight takes images that form a set of
      stereo pairs. The matching proceeds from the shortest baseline pair to the
      longest baseline pair, using the disparity map already obtained to guide in
      searching for the next pair.

PMID- 21869405
TI  - Localizing overlapping parts by searching the interpretation tree.
AB  - This paper discusses how local measurements of positions and surface normals may
      be used to identify and locate overlapping objects. The objects are modeled as
      polyhedra (or polygons) having up to six degrees of positional freedom relative
      to the sensors. The approach operates by examining all hypotheses about pairings
      between sensed data and object surfaces and efficiently discarding inconsistent
      ones by using local constraints on: distances between faces, angles between face
      normals, and angles (relative to the surface normals) of vectors between sensed
      points. The method described here is an extension of a method for recognition and
      localization of nonoverlapping parts previously described in [18] and [15].

PMID- 21869406
TI  - Using polygons to recognize and locate partially occluded objects.
AB  - We present computer vision algorithms that recognize and locate partially
      occluded objects. The scene may contain unknown objects that may touch or overlap
      giving rise to partial occlusion. The algorithms revolve around a generate-test
      paradigm. The paradigm iteratively generates and tests hypotheses for
      compatibility with the scene until it identifies all the scene objects. Polygon
      representations of the object's boundary guide the hypothesis generation scheme.
      Choosing the polygon representation turns out to have powerful consequences in
      all phases of hypothesis generation and verification. Special vertices of the
      polygon called ''corners'' help detect and locate the model in the scene. Polygon
      moment calculations lead to estimates of the dissimilarity between scene and
      model corners, and determine the model corner location in the scene. An
      association graph represents the matches and compatibility constraints.
      Extraction of the largest set of mutually compatible matches from the association
      graph forms a model hypothesis. Using a coordinate transform that maps the model
      onto the scene, the hypothesis gives the proposed model's location and
      orientation. Hypothesis verification requires checking for region consistency.
      The union of two polygons and other polygon operations combine to measure the
      consistency of the hypothesis with the scene. Experimental results give examples
      of all phases of recognizing and locating the objects.

PMID- 21869407
TI  - Multiple resolution skeletons.
AB  - This paper presents a new algorithm to compute skeletons of noisy images of
      objects which can be described as ''amorphous blobs.'' Such a requirement arose
      from our research to obtain a better understanding of the role of the pseudopod
      in leukocyte locomotion. It involves the modeling and detection of pseudopods
      which are by their nature nonrigid bodies appearing on the cell's surface
      membrane. By computing skeletons at different resolutions, a filtered version can
      be produced without violating the constraints imposed by the semantic knowledge
      of pseudopod morphology. The filtered version incorporates all the significant
      ''events'' that occur at the different resolutions. The resolution at which the
      shape is examined is related to the degree of smoothing, in that the lower the
      resolution gets, the higher the degree of smoothing. Skeleton branches that
      persist over several scales arise from convexities that are locally as well as
      globally significant. Their stability is related to their perceptual
      significance. Our approach is to combine an initial region centered description
      (skeleton) with a boundary analysis executed at different resolutions. Having
      computed the skeleton at different scales, we then use those computed at the
      lower resolutions as a measure of how global the underlying convexity is. Clearly
      the skeletons computed at higher resolutions represent the exact location and
      orientation of the underlying convexities.

PMID- 21869408
TI  - Hierarchical shape description via the multiresolution symmetric axis transform.
AB  - A method is proposed that produces a shape description in the form of a hierarchy
      by scale of simple symmetric axis sequences. An axis segment that is a child of
      another has smaller scale and is seen as a branch of its parent. The scale value
      and parent-child relationship are induced by following the symmetric axis under
      successive reduction of resolution. The result, in two or three dimensions, is a
      figure?rather than boundary?oriented shape description that has natural segments
      and is insensitive to noise in the object description. The general approach of
      hierarchy production by following a feature through successive resolution
      reduction will be presented, as will methods of resolution reduction and computer
      implementation. Also, the relation of this figure-based shape description to
      those based on boundary curvature will be briefly discussed.

PMID- 21869409
TI  - Frequency domain analysis and synthesis of image pyramid generating kernels.
AB  - Construction of image pyramids is described as a two-di-mensional decimation
      process. Frequently employed generating kernels are compared to the optimal
      kernel that assures minimal information loss after the resolution reduction,
      i.e., the one corresponding to an ideal low pass filter. Physically realizable,
      optimal generating kernels are presented. The amount of computation required for
      generation of the image pyramid can be reduced significantly by employing half
      band filters as components of the optimal kernel. Image pyramids generated by the
      optimal kernel show a better command of details than the ones generated by a
      simple 4 * 4 averaging, or a computationally equivalent kernel.

PMID- 21869410
TI  - A new sense for depth of field.
AB  - This paper examines a novel source of depth information: focal gradients
      resulting from the limited depth of field inherent in most optical systems.
      Previously, autofocus schemes have used depth of field to measured depth by
      searching for the lens setting that gives the best focus, repeating this search
      separately for each image point. This search is unnecessary, for there is a
      smooth gradient of focus as a function of depth. By measuring the amount of
      defocus, therefore, we can estimate depth simultaneously at all points, using
      only one or two images. It is proved that this source of information can be used
      to make reliable depth maps of useful accuracy with relatively minimal
      computation. Experiments with realistic imagery show that measurement of these
      optical gradients can provide depth information roughly comparable to stereo
      disparity or motion parallax, while avoiding image-to-image matching problems.

PMID- 21869411
TI  - Image analysis using mathematical morphology.
AB  - For the purposes of object or defect identification required in industrial vision
      applications, the operations of mathematical morphology are more useful than the
      convolution operations employed in signal processing because the morphological
      operators relate directly to shape. The tutorial provided in this paper reviews
      both binary morphology and gray scale morphology, covering the operations of
      dilation, erosion, opening, and closing and their relations. Examples are given
      for each morphological concept and explanations are given for many of their
      interrelationships.

PMID- 21869412
TI  - Sparse decompositions for exploratory pattern analysis.
AB  - We define and verify the utility of a pattern analysis procedure called sparse
      decomposition. This technique involves sequentially ''peeling'' sparse subsets of
      patterns from a pattern set, where sparse subsets are sets of patterns which
      possess a certain degree of regularity or compactness as measured by a
      compactness measure c. If this is repeated until all patterns are deleted, then
      the sequence of decomposition ''layers'' derived by this procedure provides a
      wealth of information from which inferences about the original pattern set may be
      made. A statistic P is derived from this information and is shown to be powerful
      in detecting clustering tendency for data in reasonably compact sampling windows.
      The test is applied to both synthetic and real data.

PMID- 21869413
TI  - Extension of conditional probability and measures of belief and disbelief in a
      hypothesis based on uncertain evidence.
AB  - Conditional probability is extended so as to be conditioned by an uncertain
      proposition of which truth value is ? (0 ? ? ? 1). Using the extended conditional
      probability, the measure of increased belief and disbelief in a hypothesis
      resulting from the observation of uncertain evidence are derived from MYCIN's
      measures based on certain evidence. On the comparison with our measures, it is
      shown that MYCIN's intuitive measures based on uncertain evidence, called the
      strength of evidence, utilize affirmative information which increases belief in
      the uncertain evidence but ignore negative information which causes new doubt in
      the uncertain evidence. An interpretation of the disregard of the negative
      information is presented from the viewpoint of cognitive psychology. It is
      pointed out that this disregard of the negative information is reasonable for a
      model of human inference but the negative information must also be utilized in
      order to evaluate a hypothesis correctly, or impartially on the basis of
      uncertain evidence. Our measures provide a means for utilizing both the
      affirmative and negative information on uncertain evidence. It is shown that
      inference based on the negation of evidence, which is contained in one of our
      measures, is difficult for an expert. A method for estimating the measure is
      presented which does not demand the difficult inference from an expert. The
      significance of the method is explained from the viewpoint of cognitive
      psychology.

PMID- 21869414
TI  - A new algorithm for image edge extraction using a statistical classifier
      approach.
AB  - This correspondence describes a new algorithm for extracting edges from natural
      images. Starting from a simple image model, the algorithm poses the problem of
      edge extraction as a statistical classifier problem. The algorithm is capable of
      extracting and detecting edges from images even in the presence of noise. A step
      by step mathematical derivation of the algorithm reveals the flexibility of the
      algorithm with pertinent parameters that can be varied for the specific need of
      the user. Finally, the proposed edge operator is compared to the well-known Marr
      Hildreth's edge operator.

PMID- 21869415
TI  - Dynamic imagery modeling and motion estimation using weak formulations.
AB  - Basic research into the modeling and analysis of image sequence dynamics is
      presented. A distributed parameter system (DPS) framework and the concept of weak
      solutions are used to develop image motion estimation algorithms. These
      algorithms represent a region-oriented (as opposed to point-by-point) approach to
      image motion analysis which is theoretically justifiable, computationally
      advantageous, and leads to interesting extensions. Particularly noteworthy is the
      use of weak solution-based motion features to obtain static image structural
      information and multiple object motion estimates. Experimental results confirm
      the validity and accuracy of the approach. Future research topics are described.

PMID- 21869416
TI  - Fast Convolution with Laplacian-of-Gaussian Masks.
AB  - We present a technique for computing the convolution of an image with LoG
      (Laplacian-of-Gaussian) masks. It is well known that a LoG of variance a can be
      decomposed as a Gaussian mask and a LoG of variance a1 < a. We take advantage of
      the specific spectral characteristics of these filters in our computation: the
      LoG is a bandpass filter; we can therefore fold the spectrum of the image (after
      low pass filtering) without loss of information, which is equivalent to reducing
      the resolution. We present a complete evaluation of the parameters involved,
      together with a complexity analysis that leads to the paradoxical result that the
      computation time decreases when a increases. We illustrate the method on two
      images.

PMID- 21869417
TI  - Parallel 2-d convolution on a mesh connected array processor.
AB  - In this correspondence, a parallel 2-D convolution scheme is presented. The
      processing structure is a mesh connected array processor consisting of the same
      number of simple processing elements as the number of pixels in the image. For
      most windows considered, the number of computation steps required is the same as
      that of the coefficients of a convolution window. The proposed scheme can be
      easily extended to convolution windows of arbitrary size and shape. The basic
      idea of the proposed scheme is to apply the 1-D systolic concept to 2-D
      convolution on a mesh structure. The computation is carried out along a path
      called a convolution path in a systolic manner. The efficiency of the scheme is
      analyzed for windows of various shapes. The ideal convolution path is a
      Hamiltonian path ending at the center of the window, the length of which is equal
      to the number of window coefficients. The simple architecture and control
      strategy make the proposed scheme suitable for VLSI implementation.

PMID- 21869418
TI  - The entry-exit method of shadow boundary segmentation.
AB  - A new method has been developed for interpreting the shadows of arbitrarily
      shaped surfaces by segmenting and labeling the shadow boundary. The method is
      based on the fact that a linear projection of any light ray (the ray is assumed
      to originate at a single, distant source) across a shadow either enters or exits
      the shadow at its boundary. Hence, junctures of entry and exit segments form
      vertices that can be found directly for any given direction of illumination and
      view. Entry-exit vertices that are extremes of the boundary (which is normal to
      the axis of light) can be identified as junctures of specific profiles of the
      shadow-making object. These junctures, in turn identify the segments connected to
      them. The method assumes successful lower level extraction of shadow boundaries.
      When one object occludes part of another object's shadow, critical junctures
      occur, but these sometimes are not entry-exit vertices. These hidden junctures
      create ambiguities that must be dealt with in the context of neighboring
      segments. Certain a priori knowledge is helpful in this situation. The method may
      require knowledge of the surface or the object. The entry-exit method also
      provides a new link between the tasks of shadow boundary extraction and shape
      inference in the overall process of shadow interpretation. In conjunction with
      existing methods for the other tasks, the entry-exit method makes it possible to
      interpret arbitrarily shaped shadows.

PMID- 21869419
TI  - Segmentation and classification of range images.
AB  - The recognition of objects in three-dimensional space is a desirable capability
      of a computer vision system. Range images, which directly measure 3-D surface
      coordinates of a scene, are well suited for this task. In this paper we report a
      procedure to detect connected planar, convex, and concave surfaces of 3-D
      objects. This is accomplished in three stages. The first stage segments the range
      image into ''surface patches'' by a square error criterion clustering algorithm
      using surface points and associated surface normals. The second stage classifies
      these patches as planar, convex, or concave based on a non-parametric statistical
      test for trend, curvature values, and eigenvalue analysis. In the final stage,
      boundaries between adjacent surface patches are classified as crease or noncrease
      edges, and this information is used to merge compatible patches to produce
      reasonable faces of the object(s). This procedure has been successfully applied
      to a large number of real and synthetic images, four of which we present in this
      paper.

PMID- 21869420
TI  - Characteristics of natural scenes related to the fractal dimension.
AB  - Many objects in images of natural scenes are so complex and erratic, that
      describing them by the familiar models of classical geometry is inadequate. In
      this paper, we exploit the power of fractal geometry to generate global
      characteristics of natural scenes. In particular we are concerned with the
      following two questions: 1) Can we develop a measure which can distinguish
      between different global backgrounds (e.g., mountains and trees)? and 2) Can we
      develop a measure that is sensitive to change in distance (or scale)? We present
      a model based on fractional Brownian motion which will allow us to recover two
      characteristics related to the fractal dimension from silhouettes. The first
      characteristic is an estimate of the fractal dimension based on a least squares
      linear fit. We show that this feature is stable under a variety of real image
      conditions and use it to distinguish silhouettes of trees from silhouettes of
      mountains. Next we introduce a new theoretical concept called the average Holder
      constant and relate it mathematically to the fractal dimension. It is shown that
      this measurement is sensitive to scale in a predictable manner, and hence,
      provides the potential for use as a range indicator. Corroborating experimental
      results are presented.

PMID- 21869421
TI  - Bootstrap techniques for error estimation.
AB  - The design of a pattern recognition system requires careful attention to error
      estimation. The error rate is the most important descriptor of a classifier's
      performance. The commonly used estimates of error rate are based on the holdout
      method, the resubstitution method, and the leave-one-out method. All suffer
      either from large bias or large variance and their sample distributions are not
      known. Bootstrapping refers to a class of procedures that resample given data by
      computer. It permits determining the statistical properties of an estimator when
      very little is known about the underlying distribution and no additional samples
      are available. Since its publication in the last decade, the bootstrap technique
      has been successfully applied to many statistical estimations and inference
      problems. However, it has not been exploited in the design of pattern recognition
      systems. We report results on the application of several bootstrap techniques in
      estimating the error rate of 1-NN and quadratic classifiers. Our experiments show
      that, in most cases, the confidence interval of a bootstrap estimator of
      classification error is smaller than that of the leave-one-out estimator. The
      error of 1-NN, quadratic, and Fisher classifiers are estimated for several real
      data sets.

PMID- 21869422
TI  - Bayes Error Estimation Using Parzen and k-NN Procedures.
AB  - The use of k nearest neighbor (k-NN) and Parzen density estimates to obtain
      estimates of the Bayes error is investigated under limited design set conditions.
      By drawing analogies between the k-NN and Parzen procedures, new procedures are
      suggested, and experimental results are given which indicate that these
      procedures yield a significant improvement over the conventional k-NN and Parzen
      procedures. We show that, by varying the decision threshold, many of the biases
      associated with the k-NN or Parzen density estimates may be compensated, and
      successful error estimation may be performed in spite of these biases.
      Experimental results are given which demonstrate the effect of kernel size and
      shape (Parzen), the size of k (k-NN), and the number of samples in the design
      set.

PMID- 21869423
TI  - Decision-directed multivariate empirical bayes classification with nonstationary
      priors.
AB  - A decision-directed learning strategy is presented to recursively estimate (i.e.,
      track) the time-varying a priori distribution for a multivariate empirical Bayes
      adaptive classification rule. The problem is formulated by modeling the prior
      distribution as a finite-state vector Markov chain and using past decisions to
      estimate the time evolution of the state of this chain. The solution is obtained
      by implementing an exact recursive nonlinear estimator for the rate vector of a
      multivariate discrete-time point process representing the decisions. This
      estimator obtains the Doob decomposition of the decision process with respect to
      the a-field generated by all past decisions and corresponds to the nonlinear
      least squares estimate of the prior distribution. Monte Carlo simulation results
      are provided to assess the performance of the estimator.

PMID- 21869424
TI  - Convergence and Consistency of Fuzzy c-means/ISODATA Algorithms.
AB  - The fuzzy c-means/ISODATA algorithm is usually described in terms of clustering a
      finite data set. An equivalent point of view is that the algorithm clusters the
      support points of a finite-support probability distribution. Motivated by recent
      work on the hard version of the algorithm, this paper extends the definition to
      arbitrary distributions and considers asymptotic properties. It is shown that
      fixed points of the algorithm are stationary points of the fuzzy objective
      functional, and vice versa. When the algorithm is iteratively applied to an
      initial prototype set, the sequence of prototype sets produced approaches the set
      of fixed points. If an unknown distribution is approximated by the empirical
      distribution of stationary, ergodic observations, then as the number of
      observations grows large, fixed points of the algorithm based on the empirical
      distribution approach fixed points of the algorithm based on the true
      distribution. Furthermore, with respect to minimizing the fuzzy objective
      functional, the algorithm based on the empirical distribution is asymptotically
      at least as good as the algorithm based on the true distribution.

PMID- 21869425
TI  - Modeling and isomorphisms of positional board games.
AB  - A model is proposed for a class of two-person games based on the occupation of
      positions on a board. Well-known games that can be rephrased within or with the
      help of the model are, for example, tic-tac-toe, qubic, go-moku, hex, and connect
      four. The model is formulated in terms of a composite algebraic structure called
      board. A notion of board isomorphism is defined, a few concepts fundamental for
      positional board game playing are identified, and necessary and sufficient
      conditions for establishing the isomorphism of two boards are proved. The
      formalism of the model provides criteria for the description and analysis of a
      board that are more abstract than its physical characteristics such as size and
      dimensionality. The application of the isomorphism results to the implementation
      of more general and efficient software modules for game playing is discussed.
      Related work is briefly outlined and compared.

PMID- 21869426
TI  - Recognition of noisy subsequences using constrained edit distances.
AB  - Let X* be any unknown word from a finite dictionary H. Let U be any arbitrary
      subsequence of X*. We consider the problem of estimating X* by processing Y,
      which is a noisy version of U. We do this by defining the constrained edit
      distance between XH and Y subject to any arbitrary edit constraint involving the
      number and type of edit operations to be performed. An algorithm to compute this
      constrained edit distance has been presented. Although in general the algorithm
      has a cubic time complexity, within the framework of our solution the algorithm
      possesses a quadratic time complexity. Recognition using the constrained edit
      distance as a criterion demonstrates remarkable accuracy. Experimental results
      which involve strings of lengths between 40 and 80 and which contain an average
      of 26.547 errors per string demonstrate that the scheme has about 99.5 percent
      accuracy.

PMID- 21869427
TI  - Classification of partial 2-d shapes using fourier descriptors.
AB  - We present a method for the classification of 2-D partial shapes using Fourier
      descriptors. We formulate the problem as one of estimating the Fourier
      descriptors of the unknown complete shape from the observations derived from an
      arbitrarily rotated and scaled shape with missing segments. The method used for
      obtaining the estimates of the Fourier descriptors minimizes a sum of two terms;
      the first term of which is a least square fit to the given data subject to the
      condition that the number of missing boundary points is not known and the second
      term is the perimeter2/area of the unknown shape. Experiments with synthetic and
      real boundaries show that estimates closer to the true values of Fourier
      descriptors of complete boundaries are obtained. Also, classification experiments
      performed using real boundaries indicate that reasonable classification
      accuracies are obtained even when 20-30 percent of the data is missing.

PMID- 21869428
TI  - The adaptive hough transform.
AB  - We introduce the Adaptive Hough Transform, AHT, as an efficient way of
      implementing the Hough Transform, HT, method for the detection of 2-D shapes. The
      AHT uses a small accumulator array and the idea of a flexible iterative "coarse
      to fine" accumulation and search strategy to identify significant peaks in the
      Hough parameter spaces. The method is substantially superior to the standard HT
      implementation in both storage and computational requirements. In this
      correspondence we illustrate the ideas of the AHT by tackling the problem of
      identifying linear and circular segments in images by searching for clusters of
      evidence in 2-D parameter spaces. We show that the method is robust to the
      addition of extraneous noise and can be used to analyze complex images containing
      more than one shape.

PMID- 21869429
TI  - Least-squares fitting of two 3-d point sets.
AB  - Two point sets {pi} and {p'i}; i = 1, 2,..., N are related by p'i = Rpi + T + Ni,
      where R is a rotation matrix, T a translation vector, and Ni a noise vector.
      Given {pi} and {p'i}, we present an algorithm for finding the least-squares
      solution of R and T, which is based on the singular value decomposition (SVD) of
      a 3 * 3 matrix. This new algorithm is compared to two earlier algorithms with
      respect to computer time requirements.

PMID- 21869430
TI  - Registration of translated and rotated images using finite fourier transforms.
AB  - A well-known method for image registration is based on a conventional correlation
      between phase-only, or whitened, versions of the two images to be realigned. The
      method, covering rigid translational movements, is characterized by an
      outstanding robustness against correlated noise and disturbances, such as those
      encountered with nonuniform, time varying illumination. This correspondence
      discusses an extension of the method to cover both translational and rotational
      movements.

PMID- 21869431
TI  - Multispectral texture synthesis using fractal concepts.
AB  - Natural textures are synthesized across several spectral bands using no more than
      a single second-order descriptor for each band. The Fractal model for monochrome
      textures is used as a null-hypothesis. The eye's sensitivity to Fractal dimension
      under specific conditions is determined. Multispectral camouflage is generated to
      imitate a range of natural textures.

PMID- 21869432
TI  - Classification of sleep patterns by means of markov modeling and correspondence
      analysis.
AB  - Shown is how correspondence analysis can be used to track changes in an
      individuals' sleep pattern. Correspondence analysis was applied to sleep stage
      transition matrices computed from all-night sleep of normal, obese, and apnoetic
      subjects. Differences between the groups, and intraindividual changes in sleep
      patterns could be visualized better than with a x2-based clustering approach.

PMID- 21869433
TI  - Decoding Substitution Ciphers by Means of Word Matching with Application to OCR.
AB  - A substitution cipher consists of a block of natural language text where each
      letter of the alphabet has been replaced by a distinct symbol. As a problem in
      cryptography, the substitution cipher is of limited interest, but it has an
      important application in optical character recognition. Recent advances render it
      quite feasible to scan documents with a fairly complex layout and to classify
      (cluster) the printed characters into distinct groups according to their shape.
      However, given the immense variety of type styles and forms in current use, it is
      not possible to assign alphabetical identities to characters of arbitrary size
      and typeface. This gap can be bridged by solving the equivalent of a substitution
      cipher problem, thereby opening up the possibility of automatic translation of a
      scanned document into a standard character code, such as ASCII. Earlier methods
      relying on letter n-gram frequencies require a substantial amount of ciphertext
      for accurate n-gram estimates. A dictionary-based approach solves the problem
      using relatively small ciphertext samples and a dictionary of fewer than 500
      words. Our heuristic backtrack algorithm typically visits only a few hundred
      among the 26! possible nodes on sample texts ranging from 100 to 600 words.

PMID- 21869434
TI  - A method of recognition of arabic cursive handwriting.
AB  - In spite of the progress of machine recognition techniques of Latin, Kana, and
      Chinese characters over the two past decades, the machine recognition of Arabic
      characters has remained almost untouched. In this correspondence, a structural
      recognition method of Arabic cursively handwritten words is proposed. In this
      method, words are first segmented into strokes. Those strokes are then classified
      using their geometrical and topological properties. Finally, the relative
      position of the classified strokes are examined, and the strokes are combined in
      several steps into a string of characters that represents the recognized word.
      Experimental results on texts handwritten by two persons showed high recognition
      accuracy.

PMID- 21869435
TI  - Edge focusing.
AB  - Edge detection in a gray-scale image at a fine resolution typically yields noise
      and unnecessary detail, whereas edge detection at a coarse resolution distorts
      edge contours. We show that ''edge focusing'', i.e., a coarse-to-fine tracking in
      a continuous manner, combines high positional accuracy with good noise-reduction.
      This is of vital interest in several applications. Junctions of different kinds
      are in this way restored with high precision, which is a basic requirement when
      performing (projective) geometric analysis of an image for the purpose of
      restoring the three-dimensional scene. Segmentation of a scene using geometric
      clues like parallelism, etc., is also facilitated by the algorithm, since
      unnecessary detail has been filtered away. There are indications that an
      extension of the focusing algorithm can classify edges, to some extent, into the
      categories diffuse and nondiffuse (for example diffuse illumination edges). The
      edge focusing algorithm contains two parameters, namely the coarseness of the
      resolution in the blurred image from where we start the focusing procedure, and a
      threshold on the gradient magnitude at this coarse level. The latter parameter
      seems less critical for the behavior of the algorithm and is not present in the
      focusing part, i.e., at finer resolutions. The step length of the scale parameter
      in the focusing scheme has been chosen so that edge elements do not move more
      than one pixel per focusing step.

PMID- 21869436
TI  - An iterative thresholding algorithm for image segmentation.
AB  - A thresholding technique is developed for segmenting digital images with bimodal
      reflectance distributions under nonuniform illumination. The algorithm works in a
      raster format, thus making it an attractive segmentation tool in situations
      requiring fast data throughput. The theoretical base of the algorithm is a
      recursive Taylor expansion of a continuously varying threshold tracking function.

PMID- 21869437
TI  - Error analysis in stereo determination of 3-d point positions.
AB  - The relationship between the geometry of a stereo camera setup and the accuracy
      in obtaining three-dimensional position information is of great practical
      importance in many imaging applications. Assuming a point in a scene has been
      correctly identified in each image, its three-dimensional position can be
      recovered via a simple geometrical method known as triangulation. The probability
      that position estimates from triangulation are within some specified error
      tolerance is derived. An ideal pinhole camera model is used and the error is
      modeled as known spatial image plane quantization. A point's measured position
      maps to a small volume in 3-D determined by the finite resolution of the stereo
      setup. With the assumption that the point's actual position is uniformly
      distributed inside this volume, closed form expressions for the probability
      distribution of error in position along each coordinate direction (horizontal,
      vertical, and range) are derived. Following this, the probability that range
      error dominates over errors in the point's horizontal or vertical position is
      determined. It is hoped that the results presented will have an impact upon both
      sensor design and error modeling of position measuring systems for computer
      vision and related applications.

PMID- 21869438
TI  - Physically based simulation model for acoustic sensor robot navigation.
AB  - A computer model is described that combines concepts from the fields of
      acoustics, linear system theory, and digital signal processing to simulate an
      acoustic sensor navigation system using time-of-flight ranging. By separating the
      transmitter/receiver into separate components and assuming mirror-like
      reflectors, closed-form solutions for the reflections from corners, edges, and
      walls are determined as a function of transducer size, location, and orientation.
      A floor plan consisting of corners, walls, and edges is efficiently encoded to
      indicate which of these elements contribute to a particular pulse-echo response.
      Sonar maps produced by transducers having different resonant frequencies and
      transmitted pulse waveforms can then be simulated efficiently. Examples of
      simulated sonar maps of two floor plans illustrate the performance of the model.
      Actual sonar maps are presented to verify the simulation results.

PMID- 21869439
TI  - Feature-based tactile object recognition.
AB  - Tactile sensing offers powerful capabilities for robotic perception. Through the
      use of array-force sensors, precisely located surface information about objects
      in the workspace is available wherever the robot arm may reach. In order to use
      this information to identify objects and their placement, interpretation
      processes should employ proprioceptive information and should use tactile image
      features which reflect object characteristics. A technique is described for the
      generation of constraints on object identity and placement such that information
      from multiple sensor contacts may cooperate towards interpretation.

PMID- 21869440
TI  - Finite prolate spheroidal sequences and their applications I: generation and
      properties.
AB  - The finite prolate spheroidal sequences are those finite sequences which have
      extremal energy concentrations both in space and spatial frequency. The first
      part of the paper is devoted to a study of the eigenvalue problem defining the
      sequences. This reveals those fundamental properties of the sequences which are
      relevant in image processing applications and shows how they can be generated
      efficiently. A new version of the sampling theorem is also demonstrated.

PMID- 21869441
TI  - Synthesizing statistical knowledge from incomplete mixed-mode data.
AB  - The difficulties in analyzing and clustering (synthesizing) multivariate data of
      the mixed type (discrete and continuous) are largely due to: 1) nonuniform
      scaling in different coordinates, 2) the lack of order in nominal data, and 3)
      the lack of a suitable similarity measure. This paper presents a new approach
      which bypasses these difficulties and can acquire statistical knowledge from
      incomplete mixed-mode data. The proposed method adopts an event-covering approach
      which covers a subset of statistically relevant outcomes in the outcome space of
      variable-pairs. And once the covered event patterns are acquired, subsequent
      analysis tasks such as probabilistic inference, cluster analysis, and detection
      of event patterns for each cluster based on the incomplete probability scheme can
      be performed. There are four phases in our method: 1) the discretization of the
      continuous components based on a maximum entropy criterion so that the data can
      be treated as n-tuples of discrete-valued features; 2) the estimation of the
      missing values using our newly developed inference procedure; 3) the initial
      formation of clusters by analyzing the nearest-neighbor distance on subsets of
      selected samples; and 4) the reclassification of the n-tuples into more reliable
      clusters based on the detected interdependence relationships. For performance
      evaluation, experiments have been conducted using both simulated and real life
      data.

PMID- 21869442
TI  - A high speed string correction method using a hierarchical file.
AB  - This paper describes a high speed string correction method using a hierarchical
      file. After reviewing a string correction method based on the Levenshtein
      distance, a hierarchical file construction method is introduced. A multistage
      string correction method using this file is proposed. The lower bound of
      computational complexity is estimated, and it is shown that a multistage method
      using a special type of a hierarchical file can reduce computational labor
      greatly. The larger the number of strings considered is, the more efficient the
      method becomes. The results of computer simulations on 5374 phoneme sequences
      using two and three stage correction methods are stated. The condition for a
      multistage string correction method to obtain higher correction rates than an
      ordinary dictionary method is included.

PMID- 21869443
TI  - A parallel architecture for discrete relaxation algorithm.
AB  - Discrete relaxation techniques have proven useful in solving a wide range of
      problems in digital signal and digital image processing, artificial intelligence,
      operations research, and machine vision. Much work has been devoted to finding
      efficient hardware architectures. This paper shows that a conventional hardware
      design for a Discrete Relaxation Algorithm (DRA) suffers from O(n2m3) time
      complexity and O(n2m2) space complexity. By reformulating DRA into a parallel
      computational tree and using a multiple tree-root pipelining scheme, time
      complexity is reduced to O(nm), while the space complexity is reduced by a factor
      of 2. For certain relaxation processing, the space complexity can even be
      decreased to O(nm). Furthermore, a technique for dynamic configuring an
      architectural wavefront is used which leads to an O(n) time highly concurrent
      DRA3 architecture.

PMID- 21869444
TI  - Analysis of a sampling technique applied to biological images.
AB  - This correspondence examines the classification potential of two techniques based
      on spiral sampling of binary images of zooplankton. Image pixels are rearranged
      into a one-dimensional sequence by selecting samples in a spiral manner starting
      from the edge of the image and proceeding toward the center. The properties of
      this sample sequence are examined by Fourier transform and correlation
      techniques, using images from six major zooplankton categories of varying
      orientation and size. The ability of features extracted from spiral sequences to
      classify zooplankton samples, and their classification accuracy are investigated.

PMID- 21869445
TI  - Parallel Algorithms for Image Template Matching on Hypercube SIMD Computers.
AB  - This correspondence presents several parallel algorithms for image template
      matching on an SIMD array processor with a hypercube interconnection network. For
      an N by N image and an M by M window, the time complexity is reduced from O(N2M2)
      for the serial algorithm to O(M2/K2 + M * log2 N/K + log2 N * log2 K) for the
      N2K2-PE system (1 ? K ? M), or to O(N2M2/L2) for the L2-PE system (L ? N). With
      efficient use of the inter-PE communication network, each PE requires only a
      small local memory, many unnecessary data transmissions are eliminated, and the
      time complexity is greatly reduced.

PMID- 21869446
TI  - Local languages, the succesor method, and a step towards a general methodology
      for the inference of regular grammars.
AB  - A methodology is proposed for the inference of regular grammars from positive
      samples of their languages. It is mainly based on the generative mechanism
      associated with local languages, which allows us to obtain arbitrary regular
      languages by applying morphic operators to local languages. The actual inference
      procedure of this methodology consists of obtaining a local language associated
      with the given positive sample. This procedure, which is very simple, is always
      the same, regardless of the problem considered, while the task-dependent features
      that are desired for the inferred languages, are specified through the definition
      of certain task-appropriate symbol renaming functions (morphisms).

PMID- 21869447
TI  - Mitochondria as protean organelles: membrane processes that influence
      mitochondrial shape in yeast.
AB  - Yeast mitochondria constitute a complex dynamic tubular reticulum almost
      continually undergoing fission, fusion, and movements along cytoskeletal
      filaments. Besides machineries directly implicated in these processes, a large
      group of diverse proteins, whose exact contribution is still a matter of debate,
      also influence mitochondrial shape. This review focuses on those factors that
      seem to affect morphogenesis only indirectly, through their involvement in
      mitochondrial protein import, lipid supply, inheritance, or ion homeostasis. Many
      of them stand on the intersections of pathways contributing to mitochondrial
      biogenesis. Their absence has multiple phenotypic consequences, one of the most
      distinctive being the loss of the typical tubular shape of these organelles.

PMID- 21869448
TI  - Phospholipid transport and remodeling in health and disease.
AB  - Lipids not only form the backbone of biological membranes, but also serve as the
      source of numerous regulatory and signaling molecules. Understanding the role of
      lipids in the physiology of eukaryotic cell will help to identify mechanisms
      behind lipid-related human diseases. This minireview concentrates on two examples
      of human diseases associated with phospholipid remodeling and transport. The
      first is Barth syndrome, a severe rare genetic disorder. Barth syndrome is the
      first recognized human disease in which the primary causative factor is a
      defective remodeling of the signature mitochondrial phospholipid cardiolipin. The
      other example involves defects associated with lipid transfer proteins (LTPs).
      LTPs regulate diverse lipid-mediated cellular processes important for maintaining
      the specific composition of different cellular organelles. In vitro LTPs
      facilitate lipid transport between membranes through an aqueous environment. This
      article is not intended to be a comprehensive review of lipid-related human
      diseases; its aim is rather to stress the importance of basic lipid research in
      our advancement in the diagnosis and treatment of diseases.

PMID- 21869449
TI  - Targeting of Bcl-2 family proteins for treatment of acute leukaemia.
AB  - Many studies suggest that killing of tumour cell by commonly used therapies
      (chemotherapy, radiotherapy) is mediated primarily by induction of apoptosis.
      Therefore, resistance of tumour cells to therapy can be caused by a failure in
      the ability to initiate apoptosis. Defects in apoptosis signalling pathways are
      also one of the main features of cancer, and particularly acute leukaemia.
      Malignant cells constantly resist the effects of cellular stress (e.g. DNA
      damage, oncogene activation), which would cause death of normal cells through
      apoptosis. Dysregulation of apoptosis has therefore give rise to tumour growth,
      disease progression and resistance of malignant cells to chemotherapy. Structural
      analysis of Bcl-2 family proteins playing a key role in regulation of
      mitochondrial apoptosis together with studies of their biochemical functions have
      outlines strategies for generation of drugs, resulting in numerous novel chemical
      entities with potential to reverse resistance of malignant cells to apoptosis.
      The use of these therapeutic approaches may in the future represent a new way in
      cancer therapy with high potential to improve clinical outcome and prognosis of
      acute leukaemia patients.

PMID- 21869450
TI  - Functional characteristics of ram cooling-stored spermatozoa under the influence
      of epidermal growth factor.
AB  - The aim of the study was to examine the effects of epidermal growth factor (EGF)
      on ram sperm traits following hypothermic storage. Fresh ram ejaculates were
      diluted in Triladyl extender, pooled and divided into groups according to EGF
      doses added (0, 100, 200 or 400 ng/ml). Following 72-96 h storage at 4oC, the
      spermatozoa were stained for a plasma membrane integrity (PNA-FITC), membrane
      phosphatidylserine (PS) translocation (annexin V-Fluos) and apoptosis (Yo-Pro-1),
      and analyzed by fluorescent microscopy. Sperm motility was measured using
      computer-assisted sperm analysis (CASA) and sperm fertilizing ability was tested
      using in vitro penetration/fertilization test on bovine prematured oocytes. EGF
      increased sperm motility at all doses tested, decreased the proportion of
      spermatozoa with damaged plasma membrane (at 200 or 400 ng/ml), and decreased the
      proportion of apoptotic (Yo-Pro-1) spermatozoa when given at 200 or 400 (but not
      100) ng/ml. The proportion of spermatozoa with PS translocations (8.5%) was
      affected by neither of the EGF concentrations tested. However, fertilizing
      ability of ram sperm in the in vitro test was not improved by EGF (200 ng/ml). In
      summary, EGF when given at higher concentrations improved sperm viability and
      motility after cooling storage, but these effects were not reflected in sperm
      fertilizing ability in vitro.

PMID- 21869451
TI  - Nimodipine inhibits AP firing in cultured hippocampal neurons predominantly due
      to block of voltage-dependent potassium channels.
AB  - L-type calcium channels (LTCC) are important functional elements of hippocampal
      neurons contributing to processes like memory formation and gene expression. Mice
      lacking the Ca(V)1.2 channel in hippocampal pyramidal cells exhibited defects in
      spatial memory (Moosmang et al. 2005) and lowered frequency of repetitive action
      potential (AP) firing (Lacinova et al. 2008). We tested the contribution of LTCC
      to AP firing of cultured rat neonatal hippocampal neurons using the
      dihydropyridine channel blocker nimodipine. Ionic currents and APs were recorded
      in the whole cell patch clamp configuration. A prolonged depolarizing current
      pulse activated the firing of a series of APs. The presence of 10 MUM nimodipine
      blocked all but the first AP in series. This concentration, which is potent
      enough to completely block LTCC, inhibited about 35-50% of the total calcium
      current. In addition, nimodipine blocked about 50% of both calcium-dependent and
      voltage-dependent potassium currents whereas the sodium current was not affected.
      We suggest that nimodipine suppressed the firing of APs in cultured neonatal rat
      hippocampal neurons due to inhibition of both calcium and potassium currents.

PMID- 21869452
TI  - Harmaline-resistant mutant of Methanothermobacter thermautotrophicus with a
      lesion in Na(+)/H(+) antiport.
AB  - A spontaneous mutant of Methanothermobacter thermautotrophicus resistant to the
      Na(+)/H(+) antiporter inhibitor harmaline was isolated. The Na(+)/H(+) exchange
      activity in the mutant cells was remarkably decreased in comparison with wild
      type cells. Na(+)/H(+) antiport activity of wild-type cells grown in the high
      Na(+) concentration (125 mmol/l) was significantly increased as compared to the
      cells grown under low Na(+) concentration (6.25 mmol/l) conditions. In contrast,
      harmaline resistant mutant showed almost the same Na(+)/H(+) antiport activity
      under both these conditions. While harmaline profoundly inhibited methanogenesis
      in the wild-type, increased methanogenesis was observed both in the presence and
      absence of harmaline in the mutant strain. ATP synthesis driven by methanogenic
      electron transport was significantly enhanced in the mutant cells. The
      experimental data revealed the differential expression of A flavoprotein and
      molybdenum-containing formylmethanofuran dehydrogenase 1 subunit C in harmaline
      resistant mutant. The overexpression of these proteins might contribute to
      harmaline resistance. Taken together the results indicate that harmaline
      resistance in this mutant has arisen as a consequence of mutation(s) in
      antiporter gene(s) or protein(s) linked to antiporter activity. Moreover this
      work provides the evidence that Na(+)/H(+) exchanger deficiency in harmaline
      resistant mutant can induce overexpression of several proteins participating in
      methanogenesis.

PMID- 21869453
TI  - Response of secretory pathways Ca(2+) ATPase gene expression to
      hyperhomocysteinemia and/or ischemic preconditioning in rat cerebral cortex and
      hippocampus.
AB  - The study determines whether hyperhomocysteinemia (risk factor of brain ischemia)
      alone or in combination with ischemic preconditioning (IPC) affects the ischemia
      induced changes in gene expression of secretory pathways Ca(2+)-ATPase (SPCA1).
      Hyperhomocysteinemia was induced by subcutaneous administration of homocysteine
      (Hcy; 0.45 umol/g body weight) twice a day at 8 h intervals for 14 days. Rats
      were preconditioned by 5 min ischemia and 2 days later, 15 min of global
      forebrain ischemia was induced by four vessel occlusion. We observed that
      hyperhomocysteinemia significantly decreased the level of SPCA1 mRNA in the
      cortex. Pre-ischemic challenge was noticeable in both brain areas. In the cortex,
      pre-ischemia in Hcy group led to the abrupt stimulation of the mRNA expression by
      249% within the Hcy ischemic group and by 321% in the Hcy control. Values further
      exceeded those observed in the naive control. In the hippocampus, the differences
      between naive and Hcy groups were not observed. IPC initiated elevation of mRNA
      expression to 159% (p < 0.05) of control with Hcy and to 131% (p < 0.01) of
      ischemia with Hcy, respectively. Documented response of SPCA gene to IPC in
      hyperhomocysteinemic group might suggest a correlation of SPCA expression
      consistent with the role of cross-talks between intracellular Ca(2+) stores
      including secretory pathways in the tolerance phenomenon.

PMID- 21869454
TI  - Comparative fluorescence analysis of the bovine sperm using IVA-520 (anti-CD46
      antibody) and lectins: probable localisation of CD46 on bovine sperm membrane.
AB  - Membrane cofactor protein (CD46) is complement regulatory protein with probable
      function in the reproduction process. Expression of CD46 on human, mice, rat and
      guinea pig spermatozoa is restricted to the inner acrosomal membrane. In spite of
      the presence of anti-sperm antibodies and other potential complement activating
      agents in follicular fluid, CD46 is not expressed on the plasma membrane of
      spermatozoa as the other complement regulatory proteins (DAF and CD59) in human.
      Using dual immunofluorescence labelling with mAb IVA-520 (anti-bovine CD46) and
      various lectins with different binding pattern or monoclonal antibody ACR.4,
      targeted against intra-acrosomal protein, we excluded the expression of CD46 on
      the inner acrosomal membrane as well as in the acrosomal content but, we
      suggested the localization of this molecule on the outer acrosomal membrane and
      possibly on the plasma membrane of bovine sperm.

PMID- 21869455
TI  - Interplay among regulators of multidrug resistance in Kluyveromyces lactis.
AB  - The KlYAP1 and KlPDR1 genes encode two main transcriptional regulators involved
      in the control of multidrug resistance in Kluyveromyces lactis. Deletion of
      KlPDR1 or KlYAP1 genes in K. lactis generated strain hypersusceptible to diamide,
      benomyl, fluconazole and oligomycin. Overexpression of genes KlPDR1 or KlYAP1
      from a multicopy plasmid in the Klpdr1Delta mutant strain increased the tolerance
      of transformants to all the drugs tested. YRE response elements were found in the
      promoter of the KlPDR1 gene. Gel retardation assays confirmed the binding of
      KlYap1p to the YREs in the KlPDR1 gene promoter indicating that KlYap1p can
      control the KlPDR1 gene expression.

PMID- 21869456
TI  - Analysis of the expression of platelet antigens CD9 and CD41/61 in transgenic
      rabbits with the integrated human blood clotting factor VIII gene construct.
AB  - The objective of this research was to study the expression of cell membrane
      molecules CD9 and CD41/61 of transgenic rabbit with integrated human factor VIII
      (rhFVIII) gene construct. The expressions of these molecules have been monitored
      during two lactations of transgenic rabbits and simultaneously compared with the
      expression of the same molecules of non-transgenic rabbits. The immunochemical
      analysis by indirect immunofluorescence, ELISA and indirect immunoperoxidase
      staining of blood cells and udder tissues show that the insertion of the WAP
      hFVIII gene construct into the rabbit genome, do not influence the expression of
      cell membrane antigens CD9 and CD41/61 on the blood platelets, polymorphonuclear
      blood cells, milk somatic cells and mammary gland tissues.

PMID- 21869457
TI  - Polyamines in aging and disease.
AB  - Polyamines are polycations that interact with negatively charged molecules such
      as DNA, RNA and proteins. They play multiple roles in cell growth, survival and
      proliferation. Changes in polyamine levels have been associated with aging and
      diseases. Their levels decline continuously with age and polyamine (spermidine or
      high-polyamine diet) supplementation increases life span in model organisms.
      Polyamines have also been involved in stress resistance. On the other hand,
      polyamines are increased in cancer cells and are a target for potential
      chemotherapeutic agents. In this review, we bring together these various results
      and draw a picture of the state of our knowledge on the roles of polyamines in
      aging, stress and diseases.

PMID- 21869459
TI  - Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks
      and microvascular compromise.
AB  - The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully
      understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a
      variety of in vivo xenograft, and in vitro models to investigate the impact of
      chemotherapy-induced aging on the human ovary. Doxorubicin caused massive double
      strand-DNA-breaks in primordial follicles, oocytes, and granulosa cells in a dose
      dependent fashion as revealed by accumulating gammaH2AX foci. This damage was
      associated with apoptotic oocyte death and resulted in the activation of ATM. It
      appeared that the repair response enabled a minor proportion of oocytes (34.7%)
      and granulosa cells (12.1%) to survive while the majority succumbed to apoptotic
      death. Paradoxically, inhibition of ATM by KU-55933 resulted in improved
      survival, probably via prevention of downstream activation of TAp63alpha.
      Furthermore, doxorubicin caused vascular and stromal damage in the human ovary,
      which might impair ovarian function both pre- and post-menopausally. Chemotherapy
      induced premature ovarian aging appears to result from a complex process
      involving both the germ- and non-germ cell components of the ovary. These effects
      may have clinical implications in aging both for premenopausal and postmenopausal
      cancer survivors.

PMID- 21869458
TI  - Phosphorylation of amyloid beta (Abeta) peptides - a trigger for formation of
      toxic aggregates in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia and associated with
      the progressive accumulation of amyloid beta-peptides (Abeta) in form of
      extracellular amyloid plaques in the human brain. A critical role of Abeta in the
      pathogenesis of AD is strongly supported by gene mutations that cause early-onset
      familial forms of the disease. Such mutations have been identified in the APP
      gene itself and in presenilin 1 and 2. Importantly, all the identified mutations
      commonly lead to early deposition of extracellular plaques likely by increasing
      the generation and/or aggregation of Abeta. However, such mutations are very rare
      and molecular mechanisms that might trigger aggregation and deposition of Abeta,
      in the most common late onset AD are largely unknown. We recently demonstrated
      that extracellular Abeta undergoes phosphorylation by a cell surface-localized or
      secreted form of protein kinase A. The phosphorylation of serine residue 8
      promotes aggregation by stabilization of beta-sheet conformation of Abeta and
      increased formation of oligomeric Abeta aggregates that represent nuclei for
      fibrillization. Phosphorylated Abeta was detected in the brains of transgenic
      mice and human AD brains and showed increased toxicity in Drosophila models as
      compared with non-phosphorylated Abeta. Together, these findings demonstrate a
      novel molecular mechanism that triggers aggregation and toxicity of Abeta. Thus,
      phosphorylation of Abeta could be relevant in the pathogenesis of late onset AD.
      The identification of extracellular protein kinase A should also stimulate
      pharmacological approaches to decrease Abeta phosphorylation in the therapy
      and/or prevention of AD.

PMID- 21869460
TI  - Aging and circadian disruption: causes and effects.
AB  - The relationship between aging and daily "circadian" behavior in humans is
      bidirectional: on the one hand, dysfunction of circadian clocks promotes age
      related maladies; on the other, aging per se leads to changes and disruption in
      circadian behavior and physiology. For the latter case, recent research suggests
      that changes to both homeostatic and circadian sleep regulatory mechanisms may
      play a role. Could hormonal changes be in part responsible?

PMID- 21869461
TI  - Transparent Raman-enhancing substrates for microbiological monitoring and in situ
      pollutant detection.
AB  - Opaque Raman-enhancing substrates made of Ag nanoparticles on incompletely
      oxidized aluminum templates have been rendered transparent by an ion-drift
      process to complete the oxidation. The result shows that the transparent
      substrates exhibit high/uniform surface-enhanced Raman scattering (SERS)
      capability and good optical transmissivity, allowing for concurrent SERS
      characterization and high contrast transmission-mode optical imaging of S. aureus
      bacteria. We also demonstrate that the transparent substrates can used in
      conjunction with optical fibers as SERS sensors for in situ detection of
      malachite green down to 10(-9) M.

PMID- 21869462
TI  - A precise optical determination of nanoscale diameters of semiconductor
      nanowires.
AB  - Electrical and optical properties of semiconducting nanowires (NWs) strongly
      depend on their diameters. Therefore, a precise knowledge of their diameters is
      essential for any kind of device integration. Here, we present an optical method
      based on dark field optical microscopy to easily determine the diameters of
      individual NWs with an accuracy of a few nanometers and thus a relative error of
      less than 10%. The underlying physical principle of this method is that strong
      Mie resonances dominate the optical scattering spectra of most semiconducting NWs
      and can thus be exploited. The feasibility of this method is demonstrated using
      GaAs NWs but it should be applicable to most types of semiconducting NWs as well.
      Dark field optical microscopy shows that even slight tapering of the NWs, i.e.
      diameter variations of a few nanometers, can be detected by a visible color
      change. Abrupt diameter changes of a few nanometers, as they occur for example
      when growth conditions vary, can be determined as well. In addition a profound
      analysis of the elastic scattering properties of individual GaAs NWs is presented
      theoretically using Mie calculations as well as experimentally by dark field
      microscopy. This method has the advantage that no vacuum technique is needed, a
      fast and reliable analysis is possible based on cheap standard hardware.

PMID- 21869463
TI  - Adsorption of gas molecules on transition metal embedded graphene: a search for
      high-performance graphene-based catalysts and gas sensors.
AB  - We report an investigation on the adsorption of small gas molecules (O(2), CO,
      NO(2) and NH(3)) on pristine and various transition metal embedded graphene
      samples using a first-principles approach based on density-functional theory
      (DFT). The most stable adsorption geometry, energy, charge transfer, and magnetic
      moment of these molecules on graphene embedded with different transition metal
      elements are thoroughly discussed. Our calculations found that embedded
      transition metal elements in general can significantly enhance the interactions
      between gas molecules and graphene, and for applications of graphene-based
      catalysis, Ti and Au may be the best choices among all transition metal elements.
      We also expect a detailed analysis of the electronic structures and magnetic
      properties of these systems to shed light on future applications of graphene
      based gas sensing and spintronics.

PMID- 21869464
TI  - Effect of deposition parameters and post-deposition annealing on the morphology
      and cellular response of electrosprayed TiO2 films.
AB  - Titania films (TiO(2)) were deposited on Ti alloy substrates by
      electrohydrodynamic atomization (EHDA), also called electrospraying, and the
      morphology and phase composition of the coatings were evaluated. A range of
      TiO(2) sols (2-8 wt%) were prepared via the hydrolysis of polymeric precursors
      using isopropanol (prOH) as a solvent carrier. Stable cone-jet formation during
      the EHDA process was greatly influenced by varying the liquid physical
      properties. Deposition parameters such as sol concentration, needle-to-substrate
      distance and spray time were found to affect film morphology. Dense and
      continuous films were obtained under optimized conditions whereby a 2 wt% TiO(2)
      sol was atomized at a flow rate of 5 ul min(-1) by a needle of 300 um inner
      diameter, kept at a distance of 20 mm from the grounded substrate and operating
      at an applied voltage of 3.5-4.2 kV. The films were then crystallized by heating
      to 300-600  degrees C. Annealing increased the hydrophilicity of the films but
      did not significantly affect the surface roughness of the films. In vitro
      cellular response was determined by studying the interaction between MG63 cells
      and the films annealed at the various temperatures. MG63 cells were able to grow
      and proliferate on all the TiO(2) films, while the highest proliferation rate was
      found on the TiO(2) films annealed at 600  degrees C. Our results indicate that
      electrosprayed TiO(2) films possess great potential for biomedical applications.

PMID- 21869465
TI  - Influence of a mobile robot on the spatial behaviour of quail chicks.
AB  - Quail chicks encountered an autonomous mobile robot during their early
      development. The robot incorporated a heat source that stimulated following of
      chicks. The spatial behaviour of grown-up chicks was tested in an exploration
      test and a detour test. Chicks that grew with the mobile robot exhibited better
      spatial abilities than chicks grown with a static heat source. We discuss these
      results in the perspective of animal-robot interaction and of the role of early
      spatial experience on the behavioural development.

PMID- 21869466
TI  - The evolutionary landscape of antifolate resistance in Plasmodium falciparum.
AB  - Resistance to antifolates in Plasmodium falciparum is well described and has been
      observed in clinical settings for decades. At the molecular level, point
      mutations in the dhfr gene that lead to resistance have been identified, and the
      crystal structure of the wildtype and mutant dihydrofolate reductase enzymes have
      been solved in complex with native substrate and drugs. However, we are only
      beginning to understand the complexities of the evolutionary pressures that lead
      to the evolution of drug resistance in this system. Microbial systems that allow
      heterologous expression of malarial proteins provide a tractable way to
      investigate patterns of evolution that can inform our eventual understanding of
      the more complex factors that influence the evolution of drug resistance in
      clinical settings. In this paper we will review work in Escherichia coli and
      Saccharomyces cerevisiae expression systems that explore the fitness landscape of
      mutations implicated in drug resistance and show that (i) a limited number of
      evolutionary pathways to resistance are followed with high probability; (ii)
      fitness costs associated with the maintenance of high levels of resistance are
      modest; and (iii) different antifolates may exert opposing selective forces.

PMID- 21869467
TI  - Genetic admixture studies on four in situ evolved, two migrant and twenty-one
      ethnic populations of Tamil Nadu, south India.
AB  - We analysed the genetic structure of ~ 1000 samples representing 27 ethnic groups
      settled in Tamil Nadu, south India, derived from two linguistic families
      (Dravidians and Indo-Europeans) representing four religious groups (Hinduism,
      Islam, Christianity and Jainism) using 11 mtDNA markers. Out of 27 ethnic groups,
      four are in situ populations (Anglo-Indian, Labbai Muslim, Nadar Christian and
      south Indian Jain) and two are migrants (Gypsy and north Indian Jain) from north
      India to Tamil Nadu, and 21 are native ethnic groups. Six of the markers we used
      were monomorphic (HaeIII663, HpaI3592, AluI5176, AluI7025, AluI13262, 9-bp
      deletion) and five markers were polymorphic (DdeI10394, AluI10397, HinfI12308,
      HincII13259 and HaeIII16517). Haplogroup frequencies, genetic affinities and
      admixture analysis are based on the genotype data of polymorphic markers observed
      in these populations. Haplogroup frequencies indicate that various ethnic groups
      entered Tamil Nadu during different time periods. Genetic affinities and
      admixture estimates revealed that the ethnic groups possessing advanced knowledge
      of farming cluster in a branch (C), and could be the late arrived settlers as
      agriculture, was introduced to this region at about 5 to 3 thousand years ago. In
      situ ethnic groups appear to have arisen at various times as a result of the
      prevailing dominant socio-cultural forces. Hierarchical Hindu caste system
      created many ethnic groups in the history of its existence; some of them became
      isolated for considerable period of time. Over all, among Tamil ethnic groups, in
      spite of caste systems' rigidity, built in flexibility in the system in the form
      of hypergamy and hypogamy had allowed maternal gene flow between them.

PMID- 21869468
TI  - Intergenic spacer length variants in Old Portuguese bread wheat cultivars.
AB  - The intergenic spacer of the ribosomal DNA is highly variable, but is location
      specific in the nucleolar organizer region of the chromosomes. This study
      provides an event of high level of polymorphism / size variation and occurrence
      of 14 unique phenotypes in 48 landraces of Portuguese bread wheat cultivars for
      IGS-amplified products obtained by PCR-RFLP technique performed with TaqI. The
      attendant IGS polymorphism has been used to deduce affinities between landraces.
      Some of the high molecular weight IGS allelic variants were also probed for their
      chromosomal localization by sequential silver nitrate staining and fluorescence
      in situ hybridization. However, only the intergenic spacer allelic variant of 3.1
      kb could be successfully hybridized, and was observed to be physically located on
      the chromosome pair 1B in the NOR loci of the cultivar 'Magueija'.

PMID- 21869469
TI  - Quantitative trait loci for rice yield-related traits using recombinant inbred
      lines derived from two diverse cultivars.
AB  - The thousand-grain weight and spikelets per panicle directly contribute to rice
      yield. Heading date and plant height also greatly influence the yield. Dissection
      of genetic bases of yield-related traits would provide tools for yield
      improvement. In this study, quantitative trait loci (QTL) mapping for spikelets
      per panicle, thousand-grain weight, heading date and plant height was performed
      using recombinant inbred lines derived from a cross between two diverse
      cultivars, Nanyangzhan and Chuan7. In total, 20 QTLs were identified for four
      traits. They were located to 11 chromosomes except on chromosome 4. Seven and
      five QTLs were detected for thousand-grain weight and spikelets per panicle,
      respectively. Four QTLs were identified for both heading date and plant height.
      About half the QTLs were commonly detected in both years, 2006 and 2007. Six QTLs
      are being reported for the first time. Two QTL clusters were identified in
      regions flanked by RM22065 and RM5720 on chromosome 7 and by RM502 and RM264 on
      chromosome 8, respectively. The parent, Nanyangzhan with heavy thousand-grain
      weight, carried alleles with increased effects on all seven thousand-grain weight
      QTL, which explained why there was no transgressive segregation for thousand
      grain weight in the population. In contrast, Chuan7 with more spikelets per
      panicle carried positive alleles at all five spikelets per panicle QTL except
      qspp5. Further work on distinction between pleiotropic QTL and linked QTL is
      needed in two yield-related QTL clusters.

PMID- 21869470
TI  - Evolutionary process of a tetranucleotide microsatellite locus in
      Acipenseriformes.
AB  - The evolutionary dynamics of the tetra-nucleotide microsatellite locus Spl-106
      were investigated at the repeat and flanking sequences in 137 individuals of 15
      Acipenseriform species, giving 93 homologous sequences, which were detected in 11
      out of 15 species. Twenty-three haplotypes of flanking sequences and three
      distinct types of repeats, type I, type II and type III, were found within these
      93 sequences. The MS-Align hylogenetic method, newly applied to microsatellite
      sequences, permitted us to understand the repeat and flanking sequence evolution
      of Spl-106 locus. The flanking region of locus Spl-106 was highly conserved among
      the species of genera Acipenser, Huso and Scaphirhynchus, which diverged about
      150 million years ago (Mya). The rate of flanking sequence divergence at the
      microsatellite locus Spl-106 in sturgeons is between 0.011% and 0.079% with an
      average at 0.028% per million years. Sequence alignment and phylogenetic trees
      produced by MS-Align showed that both the flanking and repeat regions can cluster
      the alleles of different species into Pacific and Atlantic lineages. Our results
      show a synchronous evolutionary pattern between the flanking and repeat regions.
      Moreover, the coexistence of different repeat types in the same species, even in
      the same individual, is probably due to two duplication events encompassing the
      locus Spl-106 that occurred during the divergence of Pacific lineage. The first
      occured before the diversification of Pacific species (121-96 Mya) and led to
      repeat types I and II. The second occurred more recently, just before the
      speciation of A. sinensis and A. dabryanus (69-10 Mya), and led to repeat type
      III. Sequences in the same species with different repeat types probably
      corresponds to paralogous loci. This study sheds a new light on the evolutionary
      mechanisms that shape the complex microsatellite loci involving different repeat
      types.

PMID- 21869471
TI  - Phenotypic and molecular characterization of selected tomato recombinant inbred
      lines derived from the cross Solanum lycopersicum x S. pimpinellifolium.
AB  - An important trait defining fresh tomato marketability is fruit shelf life.
      Exotic germplasm of Solanum pimpinellifolium is able to prolong shelf life.
      Sixteen recombinant inbred lines with differing values of shelf life and fruit
      weight were derived by antagonistic-divergent selection from an interspecific
      cross involving Solanum pimpinellifolium. The objective of this study was to
      evaluate these recombinant inbred lines for many fruit quality traits such as
      diameter, height, size, acidity, colour, firmness, shelf life and weight, and to
      characterize them by amplified fragment length polymorphism markers. For most
      traits, a wide range of genetic variability was found and a wide range of
      molecular variation was also detected. Both sets of data allowed the
      identification of recombinant inbred lines by means of cluster analysis and
      principal component analysis. Genetic association among some amplified fragment
      length polymorphism markers and fruit quality traits, suggested by the principal
      component analysis, could be identified by single point analysis. Potential
      molecular markers underlying agronomical traits were detected in these
      recombinant inbred lines.

PMID- 21869473
TI  - RAPD and microsatellite transferability studies in selected species of Prosopis
      (section Algarobia) with emphasis on Prosopis juliflora and P. pallida.
AB  - The genus Prosopis (Leguminosae, Mimosoideae), comprises 44 species widely
      distributed in arid and semi-arid zones. Prosopis pallida (Humb. and Bonpl. ex
      Willd.) Kunth and P. juliflora (Sw.) DC. are the two species that are truly
      tropical apart from P. africana, which is native to tropical Africa (Pasiecznik
      et al. 2004), and they have been introduced widely beyond their native ranges.
      However, taxonomic confusion within the genus has hampered exploitation and
      better management of the species. The present study focusses primarily on
      evaluating the genetic relationship between Prosopis species from the section
      Algarobia, containing most species of economic importance, though P. tamarugo
      from section Strombocarpa is also included for comparison. In total, 12 Prosopis
      species and a putative P. pallida x P. chilensis hybrid were assessed for their
      genetic relationships based on RAPD markers and microsatellite transferability.
      The results show that P. pallida and P. juliflora are not closely related despite
      some morphological similarity. Evidence also agrees with previous studies which
      suggest that the grouping of series in section Algarobia is artificial.

PMID- 21869472
TI  - Cullin-5 and cullin-2 play a role in the development of neuromuscular junction
      and the female germ line of Drosophila.
AB  - Cullins confer substrate specificity to E3-ligases which are multi-protein
      complexes involved in ubiquitin-mediated protein degradation or modification.
      There are six cullin genes in Drosophila melanogaster. We have raised an antibody
      against Cul-5 and demonstrated that it expresses in neuronal and non-neuronal
      cells throughout development. In the embryonic tracheal system, Cul-5 is enriched
      at fusion sites together with E-Cadherin and Fasciclin III. Mutations of cul-5 do
      not affect tracheal development but do show defects in the organization of
      synaptic boutons at the larval neuromuscular junction where the protein is
      expressed in a subset of motoneuron terminals. Loss of function of another cullin
      gene 'cul-2' results in similar defects at the larval neuromuscular junction
      although cul-2;cul-5 double mutants do not show an enhanced phenotype. Both cul-2
      and cul-5 mutants show similar aberrations in the development of female germ
      line. Our results suggest that both of these cullin proteins participate in
      similar developmental processes.

PMID- 21869474
TI  - Association of ADAM33 gene polymorphisms with adult-onset asthma and its severity
      in an Indian adult population.
AB  - ADAM33, a member of the ADAM (a disintegrin and metalloprotease) gene family, is
      an asthma susceptibility gene originally identified by positional cloning. In the
      present study, we investigated the possible association of five single-nucleotide
      polymorphisms (SNPs) in the ADAM33 (rs511898, rs528557, rs44707, rs597980 and
      rs2787094) with adult-onset asthma in an Indian population. The study included
      175 patients with mild intermittent (n = 44), mild persistent (n = 108) or
      moderate persistent (n = 23) subgroups of asthma, and 253 nonasthmatic control
      individuals. SNPs were genotyped with the help of restriction fragment length
      polymorphism polymerase chain reaction (RFLP-PCR) method, and data were analysed
      using chi-square test and logistic regression model. Bonferroni's correction for
      multiple comparisons was applied for each hypothesis. Genotypes and allele
      frequencies of SNPs rs511898 and rs528557 were significantly associated with
      adult-onset asthma (P = 0.010-<0.001). A significant association of the
      homozygous mutant genotype and mutant alleles of SNPs rs2787094, rs44707 and
      rs597980 with the asthma was also observed (P = 0.020-<0.001). A positive
      association between asthma and haplotypes AGCCT, GGCCT, AGACT, GCAGT, GGACT,
      ACCCC and AGACC were also found (P = 0.036-<0.001, OR = 2.07-8.49). Haplotypes
      AGCGT, GCAGC, ACAGC, ACAGT, GGAGC and GGCGT appear to protect against asthma (P =
      0.013-<0.0001, OR = 0.34-0.10). Our data suggest that ADAM33 gene polymorphisms
      serve as genetic risk factors for asthma in Indian adult population.

PMID- 21869476
TI  - Molecular cytogenetic characterization of a new wheat Secale africanum 2R(a)(2D)
      substitution line for resistance to stripe rust.
AB  - A stable, highly fertile wheat Secale africanum substitution line LF24, derived
      from the F7 generation of a cross between Mianyang11 (MY11) and Triticum durum,
      S. africanum amphiploid (YF) was identified through molecular cytogenetic
      analysis. Application of C-banding, in situ hybridization and molecular markers
      analysis showed that LF24 was a wheat S. africanum 2R(a)(2D) substitution line.
      When inoculated with stripe rust isolates, T. durum and MY11 were highly
      susceptible, while S. africanum, YF and LF24 were immune. It is confirmed through
      molecular cytogenetic analysis that the stripe rust resistance of LF24 was
      derived from S. africanum chromosome 2R(a). We compared the banding patterns and
      disease resistance of reported chromosomes 2R from different S. cereale
      introduced into wheat background, and found that there was new stripe rust
      resistance gene(s) on S. africanum 2R(a). LF24 is a new substitution line which
      can be used as stripe rust resistant source in wheat improvement.

PMID- 21869475
TI  - A new strategy for estimating two-locus recombination fractions under some
      natural inequality restrictions.
AB  - Linkage analysis is now being widely used to map markers on each chromosome in
      the human genome, to map genetic diseases, and to identify genetic forms of
      common diseases. Two-locus linkage analysis and multi-locus analysis have been
      investigated comprehensively, and many computer programs have been developed to
      perform linkage analysis. Yet there exists a shortcoming in traditional methods,
      i.e., the parameter space of two-locus recombination fractions has not been
      emphasized sufficiently in the usual analyses. In this paper, we propose a new
      strategy for estimating the two-locus recombination fractions based on data of
      backcross family in the framework of some natural and necessary parameter
      restrictions. The new strategy is based on a restricted projection algorithm,
      which can provide fast reasonable estimates of recombination fraction, and can
      therefore serve as a superior alternative algorithm. Results obtained from both
      real and simulated data indicate that the new algorithm performs well in the
      estimation of recombination fractions and outperforms current methods.

PMID- 21869477
TI  - Chromosome numbers and meiotic analysis in the pre-breeding of Brachiaria
      decumbens (Poaceae).
AB  - A total of 44 accessions of Brachiaria decumbens were analysed for chromosome
      count and meiotic behaviour in order to identify potential progenitors for
      crosses. Among them, 15 accessions presented 2n = 18; 27 accessions, 2n = 36; and
      2 accessions, 2n = 45 chromosomes. Among the diploid accessions, the rate of
      meiotic abnormalities was low, ranging from 0.82% to 7.93%. In the 27 tetraploid
      accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The
      most common meiotic abnormalities were related to irregular chromosome
      segregation, but chromosome stickiness and abnormal cytokinesis were observed in
      low frequency. All abnormalities can compromise pollen viability by generating
      unbalanced gametes. Based on the chromosome number and meiotic stability, the
      present study indicates the apomictic tetraploid accessions that can act as male
      genitor to produce interspecific hybrids with B. ruziziensis or intraspecific
      hybrids with recently artificially tetraploidized accessions.

PMID- 21869478
TI  - Thermal phenotypic plasticity of body size in Drosophila melanogaster: sexual
      dimorphism and genetic correlations.
AB  - Thirty isofemale lines collected in three different years from the same wild
      French population were grown at seven different temperatures (12-31  degrees C).
      Two linear measures, wing and thorax length, were taken on 10 females and 10
      males of each line at each temperature, also enabling the calculation of the
      wing/thorax (W/T) ratio, a shape index related to wing loading. Genetic
      correlations were calculated using family means. The W-T correlation was
      independent of temperature and on average, 0.75. For each line, characteristic
      values of the temperature reaction norm were calculated, i.e. maximum value,
      temperature of maximum value and curvature. Significant negative correlations
      were found between curvature and maximum value or temperature of maximum value.
      Sexual dimorphism was analysed by considering either the correlation between
      sexes or the female/male ratio. Female-male correlation was on average 0.75 at
      the within line, within temperature level but increased up to 0.90 when all
      temperatures were averaged for each line. The female-male ratio was genetically
      variable among lines but without any temperature effect. For the female/male
      ratio, heritability (intraclass correlation) was about 0.20 and evolvability
      (genetic coefficient of variation) close to 1. Although significant, these values
      are much less than for the traits themselves. Phenotypic plasticity of sexual
      dimorphism revealed very similar reaction norms for wing and thorax length, i.e.
      a monotonically increasing sigmoid curve from about 1.11 up to 1.17. This shows
      that the males are more sensitive to a thermal increase than females. In
      contrast, the W/T ratio was almost identical in both sexes, with only a very
      slight temperature effect.

PMID- 21869479
TI  - Role of CYP1A1 (T6235C) polymorphism and cigarette smoking in the development of
      coronary heart disease in Tunisian population.

PMID- 21869480
TI  - Interaction between COCHLEATA and UNIFOLIATA genes enables normal flower
      morphogenesis in the garden pea, Pisum sativum.

PMID- 21869481
TI  - Beneficial genotype of swine FUT1 gene governing resistance to E. coli F18 is
      associated with important economic traits.

PMID- 21869482
TI  - Characterization of two freshwater silurid catfish using conventional and
      molecular cytogenetic techniques.

PMID- 21869483
TI  - Lack of association of PTPN1 gene polymorphisms with type 2 diabetes in south
      Indians.

PMID- 21869484
TI  - Identification of novel intronic BRCA1 variants of uncertain significance in a
      Thai hereditary breast cancer family.

PMID- 21869486
TI  - Novel vitamin D 1alpha-hydroxylase gene mutations in a Chinese vitamin-D
      dependent rickets type I patient.

PMID- 21869485
TI  - No major genes in autoimmune thyroid diseases: complex segregation and
      epidemiological studies in a large Tunisian pedigree.

PMID- 21869487
TI  - Is APOE epsilon3 a favourable factor for the longevity: an association study in
      Chinese population.

PMID- 21869488
TI  - RT-PCR and real-time PCR analysis of E2A-PBX1, TEL-AML1, mBCR-ABL and MLL-AF4
      fusion gene transcripts in de novo B-lineage acute lymphoblastic leukaemia
      patients in south India.

PMID- 21869489
TI  - A quick method to calculate QTL confidence interval.

PMID- 21869490
TI  - Tumour necrosis factor alpha and interleukin 10 gene polymorphisms and the risk
      of ischemic stroke in south Indian population.

PMID- 21869491
TI  - Homozygosity for the rs9939609T allele of the FTO gene may have protective effect
      on becoming overweight in survivors of childhood acute lymphoblastic leukaemia.

PMID- 21869492
TI  - Genotyping and prenatal diagnosis of a large spinocerebellar ataxia pedigree in
      northeastern China.

PMID- 21869493
TI  - A genetic analysis of segregation distortion revealed by molecular markers in
      Lophopyrum ponticum chromosome 7E.

PMID- 21869494
TI  - Comparison of quantitative trait loci for rice yield, panicle length and spikelet
      density across three connected populations.

PMID- 21869496
TI  - Managing agricultural emissions to the atmosphere: state of the science, fate and
      mitigation, and identifying research gaps.
AB  - The impact of agriculture on regional air quality creates significant challenges
      to sustainability of food supplies and to the quality of national resources.
      Agricultural emissions to the atmosphere can lead to many nuisances, such as
      smog, haze, or offensive odors. They can also create more serious effects on
      human or environmental health, such as those posed by pesticides and other toxic
      industrial pollutants. It is recognized that deterioration of the atmosphere is
      undesirable, but the short- and long-term impacts of specific agricultural
      activities on air quality are not well known or understood. These concerns led to
      the organization of the 2009 American Chemical Society Symposium titled . An
      outcome of this symposium is this special collection of 14 research papers
      focusing on various issues associated with production agriculture and its effect
      on air quality. Topics included emissions from animal feeding operations, odors,
      volatile organic compounds, pesticides, mitigation, modeling, and risk
      assessment. These papers provide new research insights, identify gaps in current
      knowledge, and recommend important future research directions. As the scientific
      community gains a better understanding of the relationships between anthropogenic
      activities and their effects on environmental systems, technological advances
      should enable a reduction in adverse consequences on the environment.

PMID- 21869495
TI  - Hypermutation and stress adaptation in bacteria.
AB  - Hypermutability is a phenotype characterized by a moderate to high elevation of
      spontaneous mutation rates and could result from DNA replication errors, defects
      in error correction mechanisms and many other causes. The elevated mutation rates
      are helpful to organisms to adapt to sudden and unforeseen threats to survival.
      At the same time hypermutability also leads to the generation of many deleterious
      mutations which offset its adaptive value and therefore disadvantageous.
      Nevertheless, it is very common in nature, especially among clinical isolates of
      pathogens. Hypermutability is inherited by indirect (second order) selection
      along with the beneficial mutations generated. At large population sizes and high
      mutation rates many cells in the population could concurrently acquire beneficial
      mutations of varying adaptive (fitness) values. These lineages compete with the
      ancestral cells and also among themselves for fixation. The one with the
      'fittest' mutation gets fixed ultimately while the others are lost. This has been
      called 'clonal interference' which puts a speed limit on adaptation. The original
      clonal interference hypothesis has been modified recently. Nonheritable
      (transient) hypermtability conferring significant adaptive benefits also occur
      during stress response although its molecular basis remains controversial. The
      adaptive benefits of heritable hypermutability are discussed with emphasis on
      host-pathogen interactions.

PMID- 21869497
TI  - Measurement of trace gas fluxes over an unfertilized agricultural field using the
      flux-gradient technique.
AB  - Trace gas fluxes exhibit extensive spatial and temporal variability that is
      dependent on a number of factors, including meteorology, ambient concentration,
      and emission source size. Previous studies have found that agricultural
      fertilization contributes to higher fluxes of certain gases. The magnitude of
      trace gas fluxes over unfertilized crops is still uncertain. In the present
      study, deposition of ammonia (NH), nitric acid (HNO), and sulfur dioxide (SO) was
      measured over unfertilized soybean using the flux-gradient technique. The eddy
      diffusivity was estimated from eddy covariance measurements of temperature
      fluxes, resulting in K of 0.64 +/- 0.30 m s. Flux means and standard deviations
      were -0.14 +/- 0.13, -0.22 +/- 0.19, and -0.38 +/- 0.54 MUg m s for NH, HNO, and
      SO, respectively. Low concentrations of NH and HNO increased the relative
      uncertainties in the deposition velocities estimated from measured fluxes. This
      contributed to dissimilarities between deposition velocities estimated from the
      resistance analogy and deposition velocities estimated from fluxes. However, wet
      canopy conditions during the study may have led to an underestimation of
      deposition by the resistance analogy because the resistance method does not
      accurately describe the enhanced deposition rates that occur after dew formation.
      Quantification of vegetation characteristics, such as leaf wetness and apoplast
      chemistry, would be beneficial in future studies to more accurately determine
      stomatal resistance and its influence on fluxes.

PMID- 21869498
TI  - Review of airborne emissions from agricultural fumigants: design and uncertainty
      considerations for the use of the integrated horizontal flux method.
AB  - Ground-level area sources, such as those associated with the use of agricultural
      fumigants, waste disposal sites, wastewater lagoons, and other applications,
      present a challenge in terms of characterizing atmospheric flux as a function of
      time. Studies are costly in terms of field activities and laboratory analysis.
      The optimization of field study design, therefore, is essential to conduct cost
      effective research. The collection of on-field profile data for airborne
      concentration, wind speed, and wind direction can be used in conjunction with the
      integrated horizontal flux (IHF) method to empirically compute complex source
      terms as a function of time. This paper focuses on complicating factors and field
      study design issues for the use of the IHF method. Insights and examples are
      drawn from five field research studies. The methods and results of characterizing
      the uncertainty and method precision in the emission fitting for the IHF method
      also are presented.

PMID- 21869499
TI  - A standardized approach for estimating the permeability of plastic films to soil
      fumigants under various field and environmental conditions.
AB  - Minimizing atmospheric emissions of soil fumigants is critical for protecting
      human and environmental health. Covering the soil surface with a plastic tarp is
      a common approach to restrict fumigant emissions. The mass transfer of the
      fumigant vapors through the tarp is often the rate-limiting factor in fumigant
      emissions. An approach for standardizing measurements of film permeability is
      proposed that is based on determining the resistance (R) of films to diffusion of
      fumigants. Using this approach, values were determined for more than 200 film
      chemical combinations under a range of temperature, relative humidity, and film
      handling conditions. Resistance to diffusion was specific for each fumigant/film
      combination, with the largest range of values observed for the fumigant
      chloropicrin. For each fumigant, decreased with increasing temperature. Changes
      in film permeability due to increases in temperature or field installation were
      generally less than a factor of five. For one film, values determined under
      conditions of very high relative humidity (approximately 100%) were at least 100
      times lower than when humidity was very low (approximately 2%). This approach
      simplifies the selection of appropriate films for soil fumigation by providing
      rapid, reproducible, and precise measurements of their permeability to specific
      fumigants and application conditions.

PMID- 21869500
TI  - Emissions of ammonia, methane, carbon dioxide, and nitrous oxide from dairy
      cattle housing and manure management systems.
AB  - Concentrated animal feeding operations emit trace gases such as ammonia (NH3),
      methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O). The implementation
      of air quality regulations in livestock-producing states increases the need for
      accurate on-farm determination of emission rates. The objective of this study was
      to determine the emission rates of NH3, CH4, CO2, and N2O from three source areas
      (open lots, wastewater pond, compost) on a commercial dairy located in southern
      Idaho. Gas concentrations and wind statistics were measured each month and used
      with an inverse dispersion model to calculate emission rates. Average emissions
      per cow per day from the open lots were 0.13 kg NH3, 0.49 kg CH4, 28.1 kg CO2,
      and 0.01 kg N2O. Average emissions from the wastewater pond (g m(-2) d(-1)) were
      2.0 g NH3, 103 g CH4, 637 g CO2, and 0.49 g N2O. Average emissions from the
      compost facility (g m(-2) d(-1)) were 1.6 g NH3, 13.5 g CH4, 516 g CO2, and 0.90
      g N2O. The combined emissions of NH3, CH4, CO2, and N2O from the lots, wastewater
      pond and compost averaged 0.15, 1.4, 30.0, and 0.02 kg cow(-1) d(-1),
      respectively. The open lot areas generated the greatest emissions of NH3, CO2,
      and N2O, contributing 78, 80, and 57%, respectively, to total farm emissions.
      Methane emissions were greatest from the lots in the spring (74% of total), after
      which the wastewater pond became the largest source of emissions (55% of total)
      for the remainder of the year. Data from this study can be used to develop trace
      gas emissions factors from open-lot dairies in southern Idaho and potentially
      other open-lot production systems in similar climatic regions.

PMID- 21869501
TI  - Ammonia emission factors from broiler litter in barns, in storage, and after land
      application.
AB  - We measured NH3 emissions from litter in broiler houses, during storage, and
      after land application and conducted a mass balance of N in poultry houses. Four
      state-of-the-art tunnel-ventilated broiler houses in northwest Arkansas were
      equipped with NH3 sensors, anemometers, and data loggers to continuously record
      NH3 concentrations and ventilation for 1 yr. Gaseous fluxes of NH3, N2O, CH4, and
      CO2 from litter were measured. Nitrogen (N) inputs and outputs were quantified.
      Ammonia emissions during storage and after land application were measured.
      Ammonia emissions during the flock averaged approximately 15.2 kg per day-house
      (equivalent to 28.3 g NH3per bird marketed). Emissions between flocks equaled
      9.09 g NH3 per bird. Hence, in-house NH3 emissions were 37.5 g NH3 per bird, or
      14.5 g kg(-1) bird marketed (50-d-old birds). The mass balance study showed N
      inputs for the year to the four houses totaled 71,340 kg N, with inputs from
      bedding, chicks, and feed equal to 303, 602, and 70,435 kg, respectively
      (equivalent to 0.60, 1.19, and 139.56 g N per bird). Nitrogen outputs totaled
      70,396 kg N. Annual N output from birds marketed, NH3 emissions, litter or cake,
      mortality, and NO2 emissions was 39,485, 15,571, 14,464, 635, and 241 kg N,
      respectively (equivalent to 78.2, 30.8, 28.7, 1.3, and 0.5 g N per bird). The
      percent N recovery for the N mass balance study was 98.8%. Ammonia emissions from
      stacked litter during a 16-d storage period were 172 g Mg(-1) litter, which is
      equivalent to 0.18 g NH3 per bird. Ammonia losses from poultry litter broadcast
      to pastures were 34 kg N ha (equivalent to 15% of total N applied or 7.91 g NH3
      per bird). When the litter was incorporated into the pasture using a new knifing
      technique, NH3 losses were virtually zero. The total NH3 emission factor for
      broilers measured in this study, which includes losses in-house, during storage,
      and after land application, was 45.6 g NH3 per bird marketed.

PMID- 21869502
TI  - Odorants and malodors associated with land application of biosolids stabilized
      with lime and coal fly ash.
AB  - Malodor emissions limit public acceptance of using municipal biosolids as natural
      organic resources in agricultural production. We aimed to identify major odorants
      and to evaluate odor concentrations associated with land application of
      anaerobically digested sewage sludges (Class B) and their alkaline (lime and coal
      fly ash)-stabilized products (Class A). These two types of biosolids were applied
      at 12.6 tonnes ha(-1) (dry weight) to microplots of very fine clayey Vertisol in
      the Jezreel Valley, northern Israel. The volatile organic compounds (VOCs)
      emitted from the biosolids before and during alkaline stabilization and after
      incorporation into the soil were analyzed by headspace solid-phase
      microextraction followed by gas chromatography-mass spectrometry. Odor
      concentrations at the plots were evaluated on site with a Nasal Ranger field
      olfactometer that sniffed over a defined land surface area through a static
      chamber. The odors emitted by anaerobically digested sewage sludges from three
      activated sludge water treatment plants had one characteristic chemical
      fingerprint. Alkaline stabilization emitted substantial odors associated with
      high concentrations of ammonia and release of nitrogen-containing VOCs and did
      not effectively reduce the potential odor annoyance. Odorous VOCs could be
      generated within the soil after biosolids incorporation, presumably because of
      anaerobic conditions within soil-biosolids aggregates. We propose that dimethyl
      disulfide and dimethyl trisulfide, which seem to be most related to the odor
      concentrations of biosolids-treated soil, be used as potential chemical markers
      for the odor annoyance associated with incorporation of anaerobically digested
      sewage sludges.

PMID- 21869503
TI  - Using electromagnetic induction technology to predict volatile fatty acid, source
      area differences.
AB  - Subsurface measures have been adapted to identify manure accumulation on feedlot
      surfaces. Understanding where manure accumulates can be useful to develop
      management practices that mitigate air emissions from manure, such as odor or
      greenhouse gases. Objectives were to determine if electromagnetic induction could
      be used to predict differences in volatile fatty acids (VFA) and other volatiles
      produced in vitro from feedlot surface material following a simulated rain event.
      Twenty soil samples per pen were collected from eight pens with cattle fed two
      different diets using a predictive sampling approach. These samples were
      incubated at room temperature for 3 d to determine fermentation products formed.
      Fermentation products were categorized into acetate, straight-, branched-chained,
      and total VFAs. These data were used to develop calibration prediction models on
      the basis of properties measured by electromagnetic induction (EMI). Diet had no
      significant effect on mean volatile solids (VS) concentration of accumulated
      manure. However, manure from cattle fed a corn (Zea mays L.)-based diet had
      significantly ( P <= 0.1) greater mean straight-chained and total VFA generation
      than pens where wet distillers grain with solubles (WDGS) were fed. Alternately,
      pens with cattle fed a WDGS-based diet had significantly (P <= 0.05) greater
      branched-chained VFAs than pens with cattle fed a corn-based diet. Many branched
      chain VFAs have a lower odor threshold than straight-chained VFAs; therefore,
      emissions from WDGS-based diet manure would probably have a lower odor threshold.
      We concluded that diets can affect the types and quantities of VFAs produced
      following a rain event. Understanding odorant accumulation patterns and the
      ability to predict generation can be used to develop precision management
      practices to mitigate odor emissions.

PMID- 21869504
TI  - Determination of volatile organic compound emissions and ozone formation from
      spraying solvent-based pesticides.
AB  - Large-scale agricultural activities have come under scrutiny for possible
      contributions to the emission of ozone precursors. The San Joaquin Valley (SJV)
      of California is an area with intense agricultural activity that exceeds the
      federal ozone standards for more than 30 to 40 d yr(-1) and the more stringent
      state standards for more than 100 d yr(-1). Pesticides are used widely in both
      agricultural and residential subregions of the SJV, but the largest use, by
      weight of "active ingredient," is in agriculture. The objective of the study was
      to determine the role of pesticide application on airborne volatile organic
      compounds (VOC) concentrations and ozone formation in the SJV. The ozone
      formation from the pesticide formulation sprayed on commercial orchards was
      studied using two transportable smog chambers at four application sites during
      the summers of 2007 and 2008. In addition to the direct measurements of ozone
      formation, airborne VOC concentrations were measured before and after pesticide
      spraying using canister and sorbent tube sampling techniques. Soil VOC
      concentrations were also measured to understand the distribution of VOCs between
      different environmental compartments. Numerous VOCs were detected in the air and
      soil samples throughout the experiment but higher molecular weight aromatic
      hydrocarbons were the primary compounds observed in elevated concentrations
      immediately after pesticide spraying. Measurements indicate that the ozone
      concentration formed by VOC downwind of the orchard may increase up to 15 ppb
      after pesticide application, with a return back to prespray levels after 1 to 2
      d.

PMID- 21869505
TI  - Comparison of field-scale herbicide runoff and volatilization losses: an eight
      year field investigation.
AB  - An 8-yr study was conducted to better understand factors influencing year-to-year
      variability in field-scale herbicide volatilization and surface runoff losses.
      The 21-ha research site is located at the USDA-ARS Beltsville Agricultural
      Research Center in Beltsville, MD. Site location, herbicide formulations, and
      agricultural management practices remained unchanged throughout the duration of
      the study. Metolachlor [2-chloro--(2-ethyl-6-methylphenyl)--(2-methoxy-1
      methylethyl) acetamide] and atrazine [6-chloro--ethyl--(1-methylethyl)-1,3,5
      triazine-2,4-diamine] were coapplied as a surface broadcast spray. Herbicide
      runoff was monitored from a month before application through harvest. A flux
      gradient technique was used to compute volatilization fluxes for the first 5 d
      after application using herbicide concentration profiles and turbulent fluxes of
      heat and water vapor as determined from eddy covariance measurements. Results
      demonstrated that volatilization losses for these two herbicides were
      significantly greater than runoff losses ( < 0.007), even though both have
      relatively low vapor pressures. The largest annual runoff loss for metolachlor
      never exceeded 2.5%, whereas atrazine runoff never exceeded 3% of that applied.
      On the other hand, herbicide cumulative volatilization losses after 5 d ranged
      from about 5 to 63% of that applied for metolachlor and about 2 to 12% of that
      applied for atrazine. Additionally, daytime herbicide volatilization losses were
      significantly greater than nighttime vapor losses ( < 0.05). This research
      confirmed that vapor losses for some commonly used herbicides frequently exceeds
      runoff losses and herbicide vapor losses on the same site and with the same
      management practices can vary significantly year to year depending on local
      environmental conditions.

PMID- 21869506
TI  - Chloropicrin emissions after shank injection: two-dimensional analytical and
      numerical model simulations of different source methods and field measurements.
AB  - Understanding the control mechanisms of fumigant movement in soil is a
      fundamental step for developing management strategies to reduce atmospheric
      emissions. Most soil fumigants including chloropicrin (CP) are applied by shank
      injection, and the application process often leaves vertical soil fractures that
      would potentially cause preferential fumigant movement and increased emissions.
      This potential transport pathway was evaluated by comparing cumulative emissions
      and soil air concentrations of CP from direct field measurements with those
      predicted using analytical and numerical models after assuming either point or
      rectangle sources for the injected CP. Results clearly showed that shank-injected
      CP, when treated as vertical rectangle sources, produced cumulative emission
      losses similar to the field measurements. Treating the shanked CP as point
      sources caused approximately 50% underprediction than the field measurements. The
      study also demonstrated that fumigant cumulative emissions can be predicted, with
      reasonable accuracy, using either analytical or numerical simulations.

PMID- 21869507
TI  - Coupling field observations, soil modeling, and air dispersion algorithms to
      estimate 1,3-dichloropropene and chloropicrin flux and exposure.
AB  - Soil fumigants are volatile compounds applied to agricultural land to control
      nematode populations, weeds, and crop diseases. Field trials used for measuring
      fumigant loss from soil to the atmosphere encompass only a small proportion of
      the near semi-infinite parameter combinations of environmental, agronomic, and
      meteorological conditions. One approach to supplement field observations uses a
      soil physics model for fumigant emission predictions. A model is first validated
      against existing field study observations and then used to extrapolate results to
      a wider range of edaphic and climatic conditions. This work compares field
      observations of 1,3-dichloropropene and chloropicrin emissions to predictions
      from the USDA soil model CHAIN_2D. Comparison between model predictions and field
      observations for a Florida and California study had values between 0.62 to 0.81
      and 0.99 to 1.0 for discrete and cumulative emission flux, respectively. CHAIN_2D
      emission rates were then coupled to several USEPA air dispersion models (ISCST3,
      CALPUFF6) to extend emission estimates to near field air concentrations. CALPUFF6
      predicted slightly higher 1-h maximum air concentrations than ISCST3 for the same
      source strength (26.2-36.0% for setbacks between 1 and 250 m from the field edge,
      respectively). A sensitivity analysis for the CHAIN_2D/ISCST3 coupled numerical
      system is provided, with several soil and irrigation parameters consistently the
      most sensitive. Changes in the depth of incorporation, tarp material, and initial
      soil water content illustrate the predicted impact to emission strength and
      resulting near-field air concentrations with reductions of cumulative emission
      loss from 8.1 to 71% and average 1-h maximum air concentration reductions between
      6.2 and 41% depending on the mitigation strategy chosen. Additionally, a
      stochastic framework based on the published SOFEA system that couples variability
      in experiment, model sensitivity, and site specific attributes is outlined should
      regional air concentration estimates resulting from fumigant use be sought.

PMID- 21869508
TI  - Use of SOFEA to predict 1,3-D concentrations in air in high-use regions of
      California.
AB  - Methyl bromide, a commonly used soil fumigant, is being phased out per the
      Montreal Protocol and multiple fumigants are being positioned as replacements.
      Most effective soil fumigants, including methyl bromide, have the potential for
      inhalation exposure if the material volatilizes from soil. Chronic exposures for
      the fumigant 1,3-dichloropropene (1,3-D) are managed in part by the California
      Department of Pesticide Regulation by limiting the annual amount that can be used
      within a given township. A stochastic/deterministic numerical system (SOil
      Fumigant Exposure Assessment system [SOFEA]) was developed using the USEPA air
      dispersion model ISCST3, field study observations for flux loss, and links to
      Geographic Information Systems (GIS). SOFEA was used retrospectively to simulate
      concentrations of 1,3-D in air for direct comparison with monitoring program
      observations conducted by California Air Resources Board in Fresno County. These
      results indicated slight overprediction but correct magnitudes for regional air
      concentrations, especially at the higher percentiles, and provide a performance
      test. SOFEA was also used, prospectively, to predict air concentrations in
      potential future-use scenarios. These simulations of chronic air concentrations
      in two high-use 1,3-D counties of California (Ventura, Merced) consisted of 25
      contiguous townships treated either at 1.5 times the current township allocation
      (40,937 kg) or at the maximum levels of 1,3-D used between 1999 and 2006.
      Exposure predictions for large regions are necessary to evaluate chronic
      population-based lifetime exposure and risk to 1,3-D should use patterns change.
      SOFEA provides a tool to estimate regional air concentrations within high-use
      areas required for such risk assessments.

PMID- 21869509
TI  - Effect of organic material on field-scale emissions of 1,3-dichloropropene.
AB  - Soil fumigation is important for growing many fruits and vegetable crops, but
      fumigant emissions may contaminate the atmosphere. A large-scale field experiment
      was initiated to test the hypothesis that adding composted municipal green waste
      to the soil surface in an agricultural field would reduce atmospheric emissions
      of the 1,3-dichloropropene (1,3-D) after shank injection at a 133 kg ha(-1)
      application rate. Three micrometeorological methods were used to obtain fumigant
      flux density and cumulative emission values. The volatilization rate was measured
      continuously for 16 d, and the daily peak volatilization rates for the three
      methods ranged from 12 to 24 MUg m(-2) s(-1). The total 1,3-D mass that
      volatilized to the atmosphere was approximately 14 to 68 kg, or 3 to 8% of the
      applied active ingredient. This represents an approximately 75 to 90% reduction
      in the total emissions compared with other recent field, field-plot, and
      laboratory studies. Significant reductions in the volatilization of 1,3-D may be
      possible when composted municipal green waste is applied to an agricultural
      field. This methodology also provides a beneficial use and disposal mechanism for
      composted vegetative material.

PMID- 21869510
TI  - Comparisons of soil surface sealing methods to reduce fumigant emission loss.
AB  - State and federal regulatory agencies depend on quality field data for
      determining the effects of agricultural management practices on fumigant
      emissions to develop sound, science-based policies and regulations on preplant
      soil fumigants. Field plot tests, using growers' standard field operation
      procedures, were used to simultaneously determine the effectiveness of several
      commonly proposed emission reduction methods, in a trial involving shank
      injection of Telone II [a.i. 1,3-dichloropropnene (1,3-D)] to a sandy loam soil
      to a target rate of 372 kg ha(-1). The experiment was conducted in late September
      2008 in the San Joaquin Valley of California. Fumigant emissions were captured
      using dynamic flux chambers. The results showed that virtually impermeable film
      (VIF) reduced emissions >95% when compared to bare soil, and the glue joints in
      the film did not significantly affect the tarp performance. The VIF also created
      a more uniform distribution of gaseous fumigant in the soil profile, which would
      likely benefit pest control efficacy. Standard high-density polyethylene (HDPE)
      tarp reduced total 1,3-D emissions about 50% (higher than most reported values)
      in this trial, whereas postfumigation intermittent water treatments (seals)
      reduced cumulative emission losses by approximately 20%. Adding 49.4 Mg ha
      (equivalent to 20 tons per acre) of composted dairy manure to surface soils did
      not reduce 1,3-D emissions during this experiment. Use of VIF was the most
      promising technique in reducing emissions and has the potential to allow lower
      application rates while providing satisfactory pest control.

PMID- 21869511
TI  - A minimum data set of water quality parameters to assess and compare treatment
      efficiency of stormwater facilities.
AB  - Urban stormwater runoff is often of poor quality, impacting aquatic ecosystems
      and limiting the use of stormwater runoff for recreational purposes. Several
      stormwater treatment facilities (STFs) are in operation or at the pilot testing
      stage, but their efficiencies are neither well documented nor easily compared due
      to the complex contaminant profile of stormwater and the highly variable runoff
      hydrograph. On the basis of a review of available data sets on urban stormwater
      quality and environmental contaminant behavior, we suggest a few carefully
      selected contaminant parameters (the minimum data set) to be obligatory when
      assessing and comparing the efficiency of STFs. Consistent use of the minimum
      data set in all future monitoring schemes for STFs will ensure broad-spectrum
      testing at low costs and strengthen comparability among facilities. The proposed
      minimum data set includes: (i) fine fraction of suspended solids (<63 MUm), (ii)
      total concentrations of zinc and copper, (iii) total concentrations of
      phenanthrene, fluoranthene, and benzo(b,k)fluoranthene, and (iv) total
      concentrations of phosphorus and nitrogen. Indicator pathogens and other specific
      contaminants (i.e., chromium, pesticides, phenols) may be added if recreational
      or certain catchment-scale objectives are to be met. Issues that need further
      investigation have been identified during the iterative process of developing the
      minimum data set.

PMID- 21869512
TI  - Laboratory evaluation of dust-control effectiveness of pen surface treatments for
      cattle feedlots.
AB  - Emission of particulate matter (PM) is one of the major air quality concerns for
      large beef cattle feedlots. Effective treatments on the uncompacted soil and
      manure mixture of the pen surface may help in reducing PM emission from feedlots.
      A laboratory apparatus was developed for measuring dust-emission potential of
      cattle feedlot surfaces as affected by pen surface treatments. The apparatus was
      equipped with a simulated pen surface, four mock cattle hooves, and samplers for
      PM with equivalent aerodynamic diam. <= 10 MUm (PM(10)). The simulated pen
      surface had a layer of dry, loose feedlot manure with a compacted soil layer
      underneath. Mock hooves were moved horizontally on the manure layer to simulate
      horizontal action of cattle hooves on the pen surface. High-volume PM samplers
      were used to collect emitted dust. Effects of hoof speed, depth of penetration,
      and surface treatments with independent candidate materials (i.e., sawdust, wheat
      straw, hay, rubber mulch, and surface water application) on PM(10) emission
      potential of the manure layer were investigated. Our laboratory study showed
      PM(10) emission potential increased with increasing depth of penetration and hoof
      speed. Of the surface treatments evaluated, application of water (6.4 mm) and hay
      (723 g m(-2)) exhibited the greatest percentage reduction in PM(10) emission
      potential (69 and 77%, respectively) compared with the untreated manure layer.
      This study indicated application of hay or other mulch materials on the pen
      surface might be good alternative methods to control dust emission from cattle
      feedlots.

PMID- 21869513
TI  - Swine odor analyzed by odor panels and chemical techniques.
AB  - The National Research Council identified odors as a significant animal emission
      and highlighted the need to develop standardized protocols for sampling and
      analysis. The purpose of our study was to compare different odor sampling
      techniques for monitoring odors emitted from stored swine manure. In our study,
      odorous headspace air from swine manure holding tanks were analyzed by human
      panels and analytical techniques. Odorous air was analyzed by human panels using
      dynamic dilution olfactometry (DDO). Chemical analysis used acid traps for
      ammonia (NH3), fluorescence for hydrogen sulfide (H2S), and thermal desorption
      gas chromatography-mass spectrometry for volatile organic compounds (VOCs).
      Chemical analysis included the use of gas chromatography-olfactometry (GC-O) for
      determining key odorants. Chemical odorant concentrations were converted to odor
      activity values (OAVs) based on literature odor thresholds. The GC-O technique
      used was GC-SNIF. Dilution thresholds measured by different odor panels were
      significantly different by almost an order of magnitude even though the main
      odorous compound concentrations had not changed significantly. Only 5% of the key
      odorous VOCs total OAVs was recovered from the Tedlar bags used in DDO analysis.
      Ammonia was the only chemical odorant significantly correlated with DDO analysis
      in the fresh (1 wk) and aged manure. Chemical analysis showed that odor
      concentration stabilized after 5 to 7 wk and that HS was the most dominant
      odorant. In aged manure, neither volatile fatty acids (VFAs) nor HS was
      correlated with any other chemical odorant, but NH, phenols, and indoles were
      correlated, and phenols and indoles were highly correlated. Correlation of
      odorant concentration was closely associated with the origin of the odorant in
      the diet. Key odorants determined by chemical and GC-O included indoles, phenols,
      NH3, and several VFAs (butanoic, 3-methylbutanoic, and pentanoic acids).

PMID- 21869514
TI  - Fertilizer source and tillage effects on yield-scaled nitrous oxide emissions in
      a corn cropping system.
AB  - Management practices such as fertilizer or tillage regime may affect nitrous
      oxide (N2O) emissions and crop yields, each of which is commonly expressed with
      respect to area (e.g., kg N ha or Mg grain ha). Expressing N2O emissions per unit
      of yield can account for both of these management impacts and might provide a
      useful metric for greenhouse gas inventories by relating N2O emissions to grain
      production rates. The objective of this study was to examine the effects of long
      term (>17 yr) tillage treatments and N fertilizer source on area- and yield
      scaled N2O emissions, soil N intensity, and nitrogen use efficiency for rainfed
      corn ( L.) in Minnesota over three growing seasons. Two different controlled
      release fertilizers (CRFs) and conventional urea (CU) were surface-applied at 146
      kg N ha(-1) several weeks after planting to conventional tillage (CT) and no-till
      (NT) treatments. Yield-scaled emissions across all treatments represented 0.4 to
      1.1% of the N harvested in the grain. Both CRFs reduced soil nitrate intensity,
      but not N2O emissions, compared with CU. One CRF, consisting of nitrification and
      urease inhibitors added to urea, decreased N2O emissions compared with a polymer
      coated urea (PCU). The PCU tended to have lower yields during the drier years of
      the study, which increased its yield-scaled N2O emissions. The overall
      effectiveness of CRFs compared with CU in this study may have been reduced
      because they were applied several weeks after corn was planted. Across all N
      treatments, area-scaled N2O emissions were not significantly affected by tillage.
      However, when expressed per unit yield of grain, grain N, or total aboveground N,
      N2O emissions with NT were 52, 66, and 69% greater, respectively, compared with
      CT. Thus, in this cropping system and climate regime, production of an equivalent
      amount of grain using NT would generate substantially more N2O compared with CT.

PMID- 21869515
TI  - Nitrous oxide dynamics in a braided river system, New Zealand.
AB  - Recently the Intergovernmental Panel on Climate Change (IPCC) emission factor EF5
      r was revised downward to a value of 0.0025 kg N2O-N per kg NO3-N leached. It was
      not reduced further due to the continued uncertainty surrounding the dynamics of
      N2O in river systems. There have been few studies where river system N2O yields
      and fluxes have been measured. In this study, we examined the relationship
      between NO3-N and N2O-N fluxes at 10 sites along a braided river system (84 km)
      over a 397-d period. Isotopic analysis of NO3-N river water samples and the
      potential agricultural nitrogen (N) sources demonstrated that the NO3-N came from
      agricultural or sewage sources. Percent saturation of N2O varied with site and
      date (average, 114%) and correlated with river N2O-N concentrations. Modeled N2O
      fluxes (16-30 MUg m(-2) h(-1)) from five sites were strongly related to river NO3
      N concentrations ( r2 = 0.86). The modeled N2O-N fluxes ranged from 39 to 81% of
      the IPCC-derived emissions based on the NO3-N load in the river over 397 d and do
      not support further lowering of the EF5-r. Further in situ river studies are
      required to verify the N2O-N fluxes and the calculated gas transfer velocity
      values for these braided river systems.

PMID- 21869516
TI  - Nitrous oxide emissions from wastewater treatment and water reclamation plants in
      southern California.
AB  - Nitrous oxide (N2O) is a long-lived and potent greenhouse gas produced during
      microbial nitrification and denitrification. In developed countries, centralized
      water reclamation plants often use these processes for N removal before effluent
      is used for irrigation or discharged to surface water, thus making this treatment
      a potentially large source of N2O in urban areas. In the arid but densely
      populated southwestern United States, water reclamation for irrigation is an
      important alternative to long-distance water importation. We measured N2O
      concentrations and fluxes from several wastewater treatment processes in urban
      southern California. We found that N removal during water reclamation may lead to
      in situ N2O emission rates that are three or more times greater than traditional
      treatment processes (C oxidation only). In the water reclamation plants tested,
      N2O production was a greater percentage of total N removed (1.2%) than
      traditional treatment processes (C oxidation only) (0.4%). We also measured
      stable isotope ratios (deltaN and deltaO) of emitted N2O and found distinct
      deltaN signatures of N2O from denitrification (0.0 +/- 4.0 0/00) and
      nitrification reactors (-24.5 +/- 2.2 0/00), respectively. These isotope data
      confirm that both nitrification and denitrification contribute to N2O emissions
      within the same treatment plant. Our estimates indicate that N2O emissions from
      biological N removal for water reclamation may be several orders of magnitude
      greater than N2O emissions from agricultural activities in highly urbanized
      southern California. Our results suggest that wastewater treatment that includes
      biological nitrogen removal can significantly increase urban N2O emissions.

PMID- 21869517
TI  - Do mitigation strategies reduce global warming potential in the northern U.S.
      corn belt?
AB  - Agricultural management practices that enhance C sequestration, reduce greenhouse
      gas emission (nitrous oxide [N2O], methane [CH4], and carbon dioxide [CO2]), and
      promote productivity are needed to mitigate global warming without sacrificing
      food production. The objectives of the study were to compare productivity,
      greenhouse gas emission, and change in soil C over time and to assess whether
      global warming potential and global warming potential per unit biomass produced
      were reduced through combined mitigation strategies when implemented in the
      northern U.S. Corn Belt. The systems compared were (i) business as usual (BAU);
      (ii) maximum C sequestration (MAXC); and (iii) optimum greenhouse gas benefit
      (OGGB). Biomass production, greenhouse gas flux change in total and organic soil
      C, and global warming potential were compared among the three systems. Soil
      organic C accumulated only in the surface 0 to 5 cm. Three-year average emission
      of N2O and CH was similar among all management systems. When integrated from
      planting to planting, N2O emission was similar for MAXC and OGGB systems,
      although only MAXC was fertilized. Overall, the three systems had similar global
      warming potential based on 4-yr changes in soil organic C, but average rotation
      biomass was less in the OGGB systems. Global warming potential per dry crop yield
      was the least for the MAXC system and the most for OGGB system. This suggests
      management practices designed to reduce global warming potential can be achieved
      without a loss of productivity. For example, MAXC systems over time may provide
      sufficient soil C sequestration to offset associated greenhouse gas emission.

PMID- 21869518
TI  - Dissipation of 17beta-estradiol in composted poultry litter.
AB  - The excreted estrogen rate of all livestock in the United States is estimated at
      134 kg d. The influence of manure treatment on the fate of estrogens is critical
      in deciding the recycling of over 300 million dry tons of livestock produced
      annually. The effects of two common manure management practices, heated
      composting and ambient temperature decomposition, on the fate of 17beta-estradiol
      in poultry litter were determined. A mixture of poultry litter, wood chips, and
      straw was amended with [C]17beta-estradiol and allowed to undergo decomposition
      with a laboratory-scale heated composter (HC) or room temperature incubation
      (RTI) for 24 d. Radiolabel in the finished products was fractionated into water
      extractable, acetone-extractable, nonextractable, and mineralized fractions.
      Total 17beta-estradiol radioactive residues in the HC and RTI ( = 2) treatments
      were not different ( > 0.05), except that statistically less 17beta-estradiol was
      mineralized to CO during HC than RTI (1.1 vs. 10.0% for HC and RTI,
      respectively). Estrone was the major degradation product in extracts of HC and
      RTI treatments as determined by liquid chromatography/mass spectrometry analyses.
      The nonextractable residues indicated no quantitative differences among the
      humins between the treatments. An estimated 3% of the fortified estrogenicity
      remained after HC treatment, and 15% of the fortified estrogenicity remained
      after RTI treatment. If reduction of water-removable, biologically active 17beta
      estradiol is the treatment goal, then HC treatment would be slightly preferred
      over ambient temperature degradation. However, unmanaged, ambient temperature
      litter piles are less costly and time consuming for food animal producers and
      result in greater mineralization and similar immobilization of estradiol.

PMID- 21869519
TI  - Forest restoration potentials of coal-mined lands in the eastern United States.
AB  - The Appalachian region in the eastern United Sates is home to the Earth's most
      extensive temperate deciduous forests, but coal mining has caused forest loss and
      fragmentation. More than 6000 km in Appalachia have been mined for coal since
      1980 under the Surface Mining Control and Reclamation Act (SMCRA). We assessed
      Appalachian areas mined under SMCRA for forest restoration potentials. Our
      objectives were to characterize soils and vegetation, to compare soil properties
      with those of pre-SMCRA mined lands that were reforested successfully, and to
      determine the effects of site age on measured properties. Soils were sampled and
      dominant vegetation characterized at up to 10 points on each of 25 post-SMCRA
      mines. Herbaceous species were dominant on 56%, native trees on 24%, and invasive
      exotics on 16% of assessed areas. Mean values for soil pH (5.8), electrical
      conductivity (0.07 dS m(-1)), base saturation (89%), and coarse fragment content
      (50% by mass) were not significantly different from measured levels on the pre
      SMCRA forested sites, but silt+clay soil fraction (61%) was higher, bicarbonate
      extractable P (4 mg kg(-1)) was lower, and bulk density (1.20 g cm(-1)) was more
      variable and often unfavorable. Pedogenic N and bicarbonate-extractable P in
      surface soils increased with site age and with the presence of weathered rocks
      among coarse fragments. Our results indicate a potential for many of these soils
      to support productive forest vegetation if replanted and if cultural practices,
      including temporary control of existing vegetation, soil density mitigation, and
      fertilization, are applied to mitigate limitations and aid forest tree
      reestablishment and growth.

PMID- 21869520
TI  - Nitrate-nitrogen losses through subsurface drainage under various agricultural
      land covers.
AB  - Nitrate-nitrogen (NO3-N) loading to surface water bodies from subsurface drainage
      is an environmental concern in the midwestern United States. The objective of
      this study was to investigate the effect of various land covers on NO3-N loss
      through subsurface drainage. Land-cover treatments included (i) conventional corn
      ( L.) (C) and soybean [ (L.) Merr.] (S); (ii) winter rye ( L.) cover crop before
      corn (rC) and before soybean (rS); (iii) kura clover ( M. Bieb.) as a living
      mulch for corn (kC); and (iv) perennial forage of orchardgrass ( L.) mixed with
      clovers (PF). In spring, total N uptake by aboveground biomass of rye in rC, rye
      in rS, kura clover in kC, and grasses in PF were 14.2, 31.8, 87.0, and 46.3 kg N
      ha, respectively. Effect of land covers on subsurface drainage was not
      significant. The NO3-N loss was significantly lower for kC and PF than C and S
      treatments (p < 0.05); rye cover crop did not reduce NO3-N loss, but NO3-N
      concentration was significantly reduced in rC during March to June and in rS
      during July to November (p < 0.05). Moreover, the increase of soil NO3-N from
      early to late spring in rS was significantly lower than the S treatment (p <
      0.05). This study suggests that kC and PF are effective in reducing NO3-N loss,
      but these systems could lead to concerns relative to grain yield loss and change
      in farming practices. Management strategies for kC need further study to achieve
      reasonable corn yield. The effectiveness of rye cover crop on NO-N loss reduction
      needs further investigation under conditions of different N rates, wider weather
      patterns, and fall tillage.

PMID- 21869521
TI  - Nitrate controls methyl mercury production in a streambed bioreactor.
AB  - Organic carbon bioreactors provide low-cost, passive treatment of a variety of
      environmental contaminants but can have undesirable side effects in some cases.
      This study examines the production of methyl mercury (MeHg) in a streambed
      bioreactor consisting of 40 m3 of wood chips and designed to treat nitrate (NO3)
      in an agricultural drainage ditch in southern Ontario (Avon site). The reactor
      provides 30 to 100% removal of NO3-N concentrations of 0.6 to 4.4 mg L(-1), but
      sulfate (SO4(2-)) reducing conditions develop when NO3 removal is complete.
      Sulfate reducing conditions are known to stimulation the production of MeHg in
      natural wetlands. Over one seasonal cycle, effluent MeHg ranged from 0.01 to 0.76
      ng L(-1) and total Hg ranged from 1.3 to 3.4 ng L(-1). During all sampling events
      when reducing conditions were only sufficient to promote NO3(-) reduction (or
      denitrification) ( = 5, late fall 2009, winter 2010), MeHg concentrations
      decreased in the reactor and it was a net sink for MeHg (mean flux of -5.1 MUg m(
      2) yr(-1)). During all sampling events when SO4(2-) reducing conditions were
      present ( = 6, early fall 2009, spring 2010), MeHg concentrations increased in
      the reactor and it was a strong source of MeHg to the stream (mean flux of 15.2
      MUg m(-2) yr(-1)). Total Hg was consistently removed in the reactor (10 of 11
      sampling events) and was correlated to the total suspended sediment load ( r2 =
      0.69), which was removed in the reactor by physical filtration. This study shows
      that organic carbon bioreactors can be a strong source of MeHg production when
      SO4(2-) reducing conditions develop; however, maintaining NO3-N concentrations >
      0.5 mg L suppresses the production of MeHg.

PMID- 21869522
TI  - A novel framework to classify marginal land for sustainable biomass feedstock
      production.
AB  - To achieve food and energy security, sustainable bioenergy has become an
      important goal for many countries. The use of marginal lands to produce energy
      crops is one strategy for achieving this goal, but what is marginal land? Current
      definitions generally focus on a single criterion, primarily agroeconomic
      profitability. Herein, we present a framework that incorporates multiple criteria
      including profitability of current land use, soil health indicators (erosion,
      flooding, drainage, or high slopes), and environmental degradation resulting from
      contamination of surface water or groundwater resources. We tested this framework
      for classifying marginal land in the state of Nebraska and estimated the
      potential for using marginal land to produce biofuel crops. Our results indicate
      that approximately 1.6 million ha, or 4 million acres, of land (approximately 8%
      of total land area) could be classified as marginal on the basis of at least two
      criteria. Second-generation lignocellulosic bioenergy crops such as switchgrass (
      Panicum virgatum L.), miscanthus (Miscanthus giganteus), native prairie grasses,
      and short-rotation woody crops could be grown on this land in redesigned
      landscapes that meet energy and environmental needs, without significant impacts
      on food or feed production. Calculating tradeoffs between the economics of
      redesigned landscapes and current practices at the field scale is the next step
      for determining functional designs for integrating biofuel feedstock production
      into current land management practices.

PMID- 21869523
TI  - Salt additions alter short-term nitrogen and carbon mobilization in a coastal
      Oregon Andisol.
AB  - Deposition of sea salts is commonly elevated along the coast relative to inland
      areas, yet little is known about the effects on terrestrial ecosystem
      biogeochemistry. We examined the influence of NaCl concentrations on N, C, and P
      leaching from a coastal Oregon forest Andisol in two laboratory studies: a rapid
      batch extraction (approximately 1 d) and a month-long incubation using
      microlysimeters. In the rapid extractions, salt additions immediately mobilized
      significant amounts of ammonium and phosphate but not nitrate. In the month-long
      incubations, salt additions at concentrations in the range of coastal
      precipitation increased nitrate leaching from the microcosms by nearly 50% and
      reduced the mobility of dissolved organic carbon. Our findings suggest that
      coupled abiotic-biotic effects increase nitrate mobility in these soils: exchange
      of sodium for ammonium, then net nitrification. Changes in sea salt deposition to
      land and the interactions with coastal soils could alter the delivery of N and C
      to sensitive coastal waters.

PMID- 21869524
TI  - Reactivity of litter leachates from California oak woodlands in the formation of
      disinfection by-products.
AB  - Litter materials from forested watersheds can be a significant source of
      dissolved organic matter (DOM) to surface waters that can contribute to the
      formation of carcinogenic disinfection by-products (DBPs) during drinking-water
      chlorination. This study characterized the reactivity of DOM from litter
      leachates of representative vegetation in oak woodlands, a major plant community
      in the Foothill Region of California. Leachates from fresh and decomposed litter
      (duff) from two oak species, pine, and annual grasses were collected for an
      entire rainy season to evaluate their reactivity to form DBPs on chlorination.
      Relationships among specific ultraviolet absorbance (SDeltaUVA), fluorescence
      index (FI), specific differential ultraviolet absorbance (SDeltaUVA), specific
      chlorine demand (SCD), and the dissolved organic carbon:dissolved organic
      nitrogen (DOC:DON) ratio to the specific DBP formation potential (SDBP-FP) were
      examined. The DOM derived from litter materials had considerable reactivity in
      forming trihalomethanes (THMs) (1.80-3.49 mmol mol), haloacetic acid (HAAs) (1.62
      2.76 mmol mol(-1)), haloacetonitriles (HANs) (0.12-0.37 mmol mol(-1)), and
      chloral hydrate (CHD) (0.16-0.28 mmol mol). These values are comparable to other
      identified watershed sources of DBP precursors reported for the California Delta,
      such as wetlands and organic soils. Vegetation type and litter decomposition
      stage (fresh litter versus 1-5 yr-old duff) were key factors that determined
      characteristics of DOM and their reactivity to form DBPs. Pine litter had
      significantly lower specific THM formation potential compared with oak and grass,
      and decomposed duff had a greater DON content, which is a precursor of HANs and
      other nitrogenous DBPs. The SDeltaUVA and SDBP-FP were temporally variable and
      dependent on vegetation type, degree of decomposition, and environmental
      conditions. Among the optical properties of DOM, SDeltaUVA was the only parameter
      that was consistently correlated with SDBP-FP.

PMID- 21869525
TI  - The effects of multiple beneficial management practices on hydrology and nutrient
      losses in a small watershed in the Canadian prairies.
AB  - Most beneficial management practices (BMPs) recommended for reducing nutrient
      losses from agricultural land have been established and tested in temperate and
      humid regions. Previous studies on the effects of these BMPs in cold-climate
      regions, especially at the small watershed scale, are rare. In this study, runoff
      and water quality were monitored from 1999 to 2008 at the outlets of two
      subwatersheds in the South Tobacco Creek watershed in Manitoba, Canada. Five BMPs
      a holding pond below a beef cattle overwintering feedlot, riparian zone and
      grassed waterway management, grazing restriction, perennial forage conversion,
      and nutrient management-were implemented in one of these two subwatersheds
      beginning in 2005. We determined that >80% of the N and P in runoff at the
      outlets of the two subwatersheds were lost in dissolved forms, ~ 50% during
      snowmelt events and ~ 33% during rainfall events. When all snowmelt- and rainfall
      induced runoff events were considered, the five BMPs collectively decreased total
      N (TN) and total P (TP) exports in runoff at the treatment subwatershed outlet by
      41 and 38%, respectively. The corresponding reductions in flow-weighted mean
      concentrations (FWMCs) were 43% for TN and 32% for TP. In most cases, similar
      reductions in exports and FWMCs were measured for both dissolved and particulate
      forms of N and P, and during both rainfall and snowmelt-induced runoff events.
      Indirect assessment suggests that retention of nutrients in the holding pond
      could account for as much as 63 and 57%, respectively, of the BMP-induced
      reductions in TN and TP exports at the treatment subwatershed outlet. The
      nutrient management BMP was estimated to have reduced N and P inputs on land by
      36 and 59%, respectively, in part due to the lower rates of nutrient application
      to fields converted from annual crop to perennial forage. Overall, even though
      the proportional contributions of individual BMPs were not directly measured in
      this study, the collective reduction of nutrient losses from the five BMPs was
      substantial.

PMID- 21869526
TI  - Levels, distribution, and health risk of phthalate esters in urban soils of
      Beijing, China.
AB  - The content of phthalate esters (PAEs) was investigated in urban soil samples ( =
      127, 0-20 cm) collected from a business area (BU), classical garden (CL), culture
      and educational area (CU), large public green space (LA), residential area (RE),
      and roadside area (RO) in Beijing. The sum of all PAE contents ranged from 1.9 to
      3141.7 ng/g, with an average of 1139.6 +/- 727.6 ng/g. Di-n-butyl phthalate (DBP)
      and di-(2-ethylhexyl) phthalate (DEHP) were the major contaminants in the soil
      samples. The content of DEHP and DBP in the urban soil of Beijing showed
      decreasing trends from the center of the city to the suburbs, which was probably
      because the center of the city has a longer history. In addition, higher DBP
      content also occurred in the south of the city, which was caused by the existence
      of several factories that produce commodity chemical and building materials in
      these areas. Because of its greater age, less disturbance from human activity,
      and high levels of total organic carbon and black carbon in CL, PAE content in CL
      was the highest among the six types of land use, followed by RE, CU, BU, LA, and
      RO. Although in 82.6% of the soil samples, DBP content exceeded the recommended
      allowable soil content in New York, USA, health risk assessment with CalTOX and
      Monte Carlo analysis showed that the total cancer risk values of PAEs were lower
      than the acceptable cancer risk value (10(-4)) and that the risk mainly came from
      dermal uptake and inhalation exposure pathways.

PMID- 21869527
TI  - Effects of pH and manure on transport of sulfonamide antibiotics in soil.
AB  - Sulfonamide antibiotics are a commonly used group of compounds in animal
      husbandry. They are excreted with manure, which is collected in a storage lagoon
      in certain types of confined animal feeding operations. Flood irrigation of
      forage fields with this liquid manure creates the potential risk of groundwater
      contamination in areas with shallow groundwater levels. We tested the hypothesis
      that-in addition to the soil characteristics-manure as cosolute and manure pH are
      two major parameters influencing sulfonamide transport in soils. Solute
      displacement experiments in repacked, saturated soil columns were performed with
      soil (loamy sand) and manure from a dairy farm in California. Breakthrough of
      nonreactive tracer and sulfadimethoxine, sulfamethazine, and sulfamethoxazole at
      different solution pH (5, 6.5, 8.5) with and without manure was modeled using
      Hydrus-1D to infer transport and reaction parameters. Tracer and sulfonamide
      breakthrough curves were well explained by a model concept based on physical
      nonequilibrium transport, equilibrium sorption, and first-order dissipation
      kinetics. Sorption of the antibiotics was low ( K4 <= 0.7 L kg) and only weakly
      influenced by pH and manure. However, sulfonamide attenuation was significantly
      affected by both pH and manure. The mass recovery of sulfonamides decreased with
      decreasing pH, e.g., for sulfamethoxazole from 77 (pH 8.5) to 56% (pH 5). The
      sulfonamides were highly mobile under the studied conditions, but manure
      application increased their attenuation substantially. The observed attenuation
      was most likely caused by a combination of microbial transformation and
      irreversible sorption to the soil matrix.

PMID- 21869528
TI  - Preliminary evaluation of septic-system absorption-field architecture types in a
      profile-limited soil.
AB  - Managing household wastewater is an issue that affects hundreds of thousands of
      people in rural communities nationwide, many of whom rely on septic systems as
      their primary means of household wastewater disposal. Septic system absorption
      field products with architectures quite different from traditional pipe-and
      gravel systems are being installed in many states with variances from initial
      design specifications. The objective of this study was to evaluate the
      performance, as measured by the in-product height of stored solution, of four
      differing absorption-field product architecture types in a profile-limited soil
      that was loaded at the maximum allowable rate based on soil morphology. Five
      chamber, two gravel-less pipe, two polystyrene aggregate, and four pipe-and
      gravel systems were installed in a profile-limited, Captina silt loam soil (fine
      silty, siliceous, active, mesic Typic Fragiudult) and dosed with raw effluent at
      rates determined by current State of Arkansas regulations via individual
      peristaltic pumps. Free-solution monitoring ports were installed within each
      product, where the depth to free solution was measured periodically and used to
      evaluate product performance. Data collected from January through August 2009
      indicated that preliminary system performance was unaffected by product
      architecture type. All products performed similarly under dry soil conditions.
      However, differences among individual products were observed during periods of
      hydrologic stress (i.e., wet soil conditions). Surfacing of effluent was not
      observed atop any product, indicating that the current loading rate design method
      is functioning properly. Preliminary results indicate that some alternative
      absorption-field products perform similarly to the traditional pipe-and-gravel
      system, thus providing flexibility and options for homeowners.

PMID- 21869529
TI  - Chemical evaluation of odor reduction by soil injection of animal manure.
AB  - Field application of animal manure is a major cause of odor nuisance in the local
      environment. Therefore, there is a need for methods for measuring the effect of
      technologies for reducing odor after manure application. In this work, chemical
      methods were used to identify key odorants from field application of pig manure
      based on experiments with surface application by trailing hoses and soil
      injection. Results from three consecutive years of field trials with full-scale
      equipment are reported. Methods applied were: membrane inlet mass spectrometry
      (MIMS), proton-transfer-reaction mass spectrometry (PTR-MS), gold-film hydrogen
      sulfide (H2S) detection, all performed on site, and thermal desorption gas
      chromatography with mass spectrometry (TD-GC/MS) based on laboratory analyses of
      field samples. Samples were collected from a static flux chamber often used for
      obtaining samples for dynamic olfactometry. While all methods were capable of
      detecting relevant odorants, PTR-MS gave the most comprehensive results. Based on
      odor threshold values, 4-methylphenol, H2S, and methanethiol are suggested as key
      odorants. Significant odorant reductions by soil injection were consistently
      observed in all trials. The flux chamber technique was demonstrated to be
      associated with critical errors due to compound instabilities in the chamber.
      This was most apparent for H2S, on a time scale of a few minutes, and on a longer
      time scale for methanethiol.

PMID- 21869531
TI  - Complex formation, phosphorylation, and localization of protein kinase A of
      Schizosaccharomyces pombe upon glucose starvation.
AB  - Nine sam mutants that undergo sexual differentiation without requiring starvation
      in Schizosaccharomyces pombe were previously isolated. In this study, we
      identified a nonsense mutation on the pka1 locus in the sam6 mutant. pka1 encodes
      a catalytic subunit of protein kinase A (PKA). Replacement and overexpression of
      pka1 suppressed the KCl sensitivity and hyper-mating phenotype of sam6,
      confirming that sam6 is an allele of pka1. To characterize further the regulation
      of Pka1, we tested the physical interaction between Pka1 and Cgs1 (a regulatory
      subunit of PKA). Pka1 and Cgs1 physically interacted under glucose-limited
      conditions but not under glucose-rich conditions. In addition, the formation of a
      Pka1-Cgs1 complex was detected under glucose-limited conditions by Blue Native
      PAGE. Furthermore, the Pka1 protein was found to be phosphorylated under glucose
      starved conditions, and at the same time its localization shifted from the
      nucleus towards the cytoplasm (mainly the vacuoles), suggesting a strong
      relationship among phosphorylation, complex formation, and the cytoplasmic
      distribution of Pka1.

PMID- 21869532
TI  - Cardiovascular event risk assessment using myocardial perfusion imaging with a
      view to wide clinical application.

PMID- 21869533
TI  - Association between epicardial adipose tissue volumes on 3-dimensional
      reconstructed CT images and recurrence of atrial fibrillation after catheter
      ablation.
AB  - BACKGROUND: Whether epicardial adipose tissue (EAT) is independently associated
      with atrial fibrillation (AF) and outcome after catheter ablation (CA) for AF
      remains unclear. METHODS AND RESULTS: Three-dimensional volume-rendering
      reconstructed images of EAT (total EAT) and EAT surrounding the left atrium (LA
      EAT) were measured on 320-row multidetector computed tomography in 40 patients
      with AF (paroxysmal AF [PAF], n = 24; persistent AF [PerAF], n = 16) who
      underwent CA, and in 37 age-matched control patients. EAT volumes were as follows
      for the control, PAF and PerAF patients: total EAT, 138.3 +/- 45.2 cm3 vs. 158.3
      +/- 47.2 cm3 vs. 226.4 +/- 93.3 cm3 (P<0.01 for control or PAF vs. PerAF); LA
      EAT, 32.9 +/- 14.5 cm3 vs. 41.3 +/- 15.3 cm3 vs. 66.8 +/- 35.1 cm3 (P < 0.001 for
      control or PAF vs. PerAF). EAT volume was independently associated with the
      presence of AF after adjustment for possible confounding factors. EAT volume was
      significantly greater in patients with lone AF than in control patients (total
      EAT, 132.8 +/- 33.3 cm3 vs. 106.2 +/- 27.3 cm3, P=0.021; LA-EAT: 34.0 +/- 10.6
      cm3 vs. 21.8 +/- 6.9 cm3, P = 0.0006). EAT volumes were greater in the 15 AF
      patients (37.5%) with post-ablation recurrence than in patients without
      recurrence (total EAT: 239.0 +/- 90.2 cm3 vs. 153.5 +/- 42.7 cm3, P=0.0002; LA
      EAT: 69.6 +/- 35.5 cm3 vs. 40.7 +/- 13.9 cm3, P=0.0008). CONCLUSIONS: EAT volume
      increases in AF patients independent of conventional risk factors and is greater
      in patients with lone AF than in non-AF patients. EAT volume might be useful for
      predicting AF recurrence after CA.

PMID- 21869534
TI  - Wolff-Parkinson-White syndrome and a left atrial "mass". Is there a link?

PMID- 21869536
TI  - Prognostic significance of carcinoma extension from primary lesions and
      metastatic nodes in papillary thyroid carcinoma: appropriateness of three
      subdivisions of extension.
AB  - Carcinoma extension to adjacent organs is an important prognostic factor in
      papillary thyroid carcinoma (PTC).  However, the biological behavior of PTC with
      carcinoma extension varies according to the degree of extension.  In this study,
      we investigated whether and how subdivision of PTC extension accurately reflects
      patients' prognosis, using a series of 5508 patients with PTC without distant
      metastasis at presentation, who underwent initial surgery between 1988 and 2004. 
      We classified extension from primary lesions or metastatic nodes into 4 grades
      based on intraoperative findings (Grade 0-4,  Grades 3 and 4 were subdivision of
      T4a).  Prognostic significance for disease-free and cause-specific survivals (DFS
      and CSS) of extension from primary lesions did not differ from that of extension
      from metastatic nodes in the same grades except for DFS of Grade 3 patients.  DFS
      of patients became worse with higher grades and CSS was also significantly linked
      to advanced grades except for Grade 1.  On multivariate analysis, Grades 1, 2 and
      3 and Grades 2 and 3 were independent prognostic factors for DFS and CSS,
      respectively, together with other conventional prognostic factors.  Taken
      together, extension from metastatic nodes has a prognostic significance
      equivalent to that from primary lesions if classified in the same grades. 
      Subdivision of PTC extension corresponding to T4a into two grades can accurately
      reflect the biological behavior of PTC.

PMID- 21869535
TI  - Individual differences in pharmacokinetics and pharmacodynamics of anesthetic
      agent propofol with regard to CYP2B6 and UGT1A9 genotype and patient age.
AB  - Propofol (2,6-diisopropylphenol) is administered intravenously for induction and
      maintenance of anesthesia; however, cases of progressive myocardial failure
      (propofol syndrome) related to the use of propofol have been reported. In the
      present study, the individual differences in pharmacokinetics and/or
      pharmacodynamics of propofol were investigated in patients who were genotyped for
      CYP2B6 and UGT1A9. Fifty-one patients treated with propofol in St. Marianna
      University Hospital were recruited for this study and provided written informed
      consent. The following parameters were analyzed: awakening time as a
      pharmacodynamic parameter, duration of propofol infusion, drug concentration in
      plasma after treatment, genotypes of CYP2B6 and UGT1A9, and age (42-84 years,
      mean of 65 years). Propofol was rapidly cleared from the blood of the subjects as
      a result of distribution and elimination. The awakening time after stopping
      propofol infusion was significantly correlated with the duration of infusion and
      the maximum concentration of propofol in these subjects. The maximum plasma
      concentration of propofol after normalizing with the duration of infusion was
      affected by the CYP2B6 G516T variant (related to impaired function) and was
      significantly affected by a propofol risk index score that incorporated CYP2B6
      G516T and UGT1A9 I399C>T (high expression) genotypes and advanced age. These
      results provide important information indicating that the genotypes of the two
      enzymes studied and advanced age are combinative determinant factors of the
      pharmacokinetics and/or pharmacodynamics of propofol.

PMID- 21869537
TI  - Relationship of 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate
      dehydrogenase gene polymorphisms with metabolic syndrome and type 2 diabetes.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive
      glucocorticoid to active glucocorticoid, plays a critical role in the
      pathogenesis of visceral obesity, metabolic syndrome, and diabetes.  Hexose-6
      phosphate dehydrogenase (H6PD) supplies a crucial cofactor, reduced nicotinamide
      adenine dinucleotide phosphate (NADPH), which allows HSD11B1 to maintain
      reductase activity.  The association of common SNPs in HSD11B1 [IVS3-29G/T
      (rs12086634), IVS4-11120A/G (rs1000283)] and H6PD [R453Q (rs6688832), P554L
      (rs17368528)], either separately or combined, with type 2 diabetes and metabolic
      syndrome was examined in 427 Korean subjects with type 2 diabetes and in 358
      nondiabetic Korean subjects.  HSD11B1 polymorphisms (rs12086634 and rs1000283)
      were associated with metabolic syndrome among type 2 diabetic subjects and an
      H6PD polymorphism (rs17368528) was a risk factor for metabolic syndrome in
      nondiabetic subjects.  However, no significant association of these SNPs with
      type 2 diabetes and metabolic syndrome was found after considering the multiple
      comparisons in the total study population.  In conclusion, HSD11B1 and H6PD
      polymorphisms may not be associated with type 2 diabetes and metabolic syndrome. 
      Further investigation of the role of these gene polymorphisms on the pathogenesis
      of metabolic syndrome is required.

PMID- 21869538
TI  - Functional characterization of insulin receptor gene mutations contributing to
      Rabson-Mendenhall syndrome - phenotypic heterogeneity of insulin receptor gene
      mutations.
AB  - Rabson-Mendenhall syndrome (RMS) is a rare disorder that presents as severe
      insulin resistance as a result of mutations present in the insulin receptor
      (INSR).  A Chinese girl with RMS presented with profound diabetes,
      hyperinsulinemia, acanthosis nigricans, hirsutism, and abnormalities of teeth and
      nails.  Direct sequencing of the patient's INSR detected heterozygote mutations
      at Arg83Gln (R83Q) and Ala1028Val (A1028V), with the former representing a novel
      mutation.  Functional studies of Chinese hamster ovary (CHO) cells transfected
      with wild-type (WT) and mutant forms of INSR were performed to evaluate the
      effects of these mutations on receptor expression and activation.  Receptor
      expression, insulin binding activity, and phosphorylation of the R83Q variant
      were comparable to WT.  In contrast, expression of the A1028V receptor was much
      lower than that of WT INSR, and impairment of insulin binding and
      autophosphorylation were nearly commensurate with the decrease in expression
      detected.  Reductions in the phosphorylation of IRS-1, Akt, and Erk1/2 (60%, 40%,
      and 50% of WT, respectively) indicate that the A1028V receptor contributes to
      impaired signal transduction.  In conclusion, INSR mutations associated with RMS
      were identified.  Moreover, the A1028V mutation associated with a decrease in
      expression of INSR potentially accounts for loss of function of the INSR.

PMID- 21869539
TI  - Effects of miglitol in combination with intensive insulin therapy on blood
      glucose control with special reference to incretin responses in type 1 diabetes
      mellitus.
AB  - To determine whether miglitol administration improves glycemic control and
      reduces the frequency of hypoglycemia in type 1 diabetes mellitus (T1DM) patients
      treated with intensive insulin therapy, we analyzed the effect of miglitol on
      daily insulin doses, body weight, hypoglycemia, and incretin hormone responses
      during meal tolerance tests (MTT).  Eleven T1DM subjects (21-77 years) undergoing
      intensive insulin therapy, took 25 mg (weeks 0-4) and 50 mg miglitol (weeks 4-12)
      thrice daily, immediately before meals.  At weeks 0 and 12, 9 of 11 subjects
      underwent MTT.  In present study, mean HbA1c, glycoalbumin, and 1,5
      anhydroglucitol levels were significantly improved.  The blood glucose level 1 h
      after dinner was significantly lower at week 12 than at week 0 (p = 0.008).  From
      week 0 to 12, there was a significant decrease in the body mass index (BMI; p =
      0.0051), frequency of preprandial hypoglycemic events (p = 0.012), and daily
      bolus insulin dosage (p = 0.018).  The change in active glucagon-like peptide-1
      (GLP-1) at 120 min significantly increased at week 12 (p = 0.015).  The change in
      total glucose-dependent insulinotropic peptide (GIP) significantly decreased in
      the MTT at week 12.  These results demonstrate that addition of miglitol on
      intensive insulin therapy in T1DM patients has beneficial effects on reducing
      BMI, bolus and total insulin dosage, and frequency of preprandial hypoglycemic
      events.  MTT findings suggest that this combination therapy improves blood
      glucose control by delaying carbohydrate absorption and modifying the responses
      of incretins, GIP, and GLP-1.

PMID- 21869540
TI  - [Evaluation of low-contrast detectability in low-dose chest computed tomography].
AB  - We investigated whether low-contrast resolution evaluation can be applied to
      chest (lung field) computed tomography (CT) images that are commonly
      reconstructed using filter kernels with strong frequency emphasis and displayed
      at wide window widths. We assumed low dose chest CT examinations and set the
      current-time product to 5 and 10 mAs. The visual detection study was performed by
      five radiological technologists using water phantom images in which the simulated
      low contrast objects (disc objects) were implanted. In addition, values of the
      low contrast detectability index (LCDI) based on a signal-to-noise ratio theorem
      were calculated from the modulation transfer factor, noise power spectrum, and
      the object's spectrum for each combination of object size, contrast, current-time
      product, and kernel. The detectability results correlated well with the LCDI
      values and correlated less well with the contrast-to-noise ratio results. These
      results were consistent with the results of past reports on abdomen images.
      Therefore, our results indicated that low contrast sensitivity can be applied to
      chest CT images as well as abdominal ones.

PMID- 21869541
TI  - [A comparative study of electrocardiogram multi-segment reconstruction and dual
      source computed tomography using a computer controlled coronary phantom].
AB  - Currently, there are two main methods for improving temporal resolution of
      coronary computed tomography (CT): electrocardiogram-gated multi-segment
      reconstruction (EMR) and dual source scanning using dual source CT (DSCT). We
      developed a motion phantom system for image quality assessment of cardiac CT to
      evaluate these two methods. This phantom system was designed to move an object at
      arbitrary speeds during a desired phase range in cyclic motion. By using this
      system, we obtained coronary CT mode images for motion objects like coronary
      arteries. We investigated the difference in motion artifacts between EMR and the
      DSCT using a 3-mm-diameter acrylic rod resembling the coronary artery. EMR was
      evaluated using 16-row multi-slice CT (16MSCT). To evaluate the image quality, we
      examined the degree of motion artifacts by analyzing the profiles around the rod
      and the displacement of a peak pixel in the rod image. In the 16MSCT, remarkable
      increases of artifacts and displacement were caused by the EMR. In contrast, the
      DSCT presented excellent images with fewer artifacts. The results showed the
      validity of DSCT to improve true temporal resolution.

PMID- 21869542
TI  - [Improved visualization of long-axis black-blood imaging of the carotid arteries
      using phase sensitive inversion recovery combined with 3D IR-T1TFE].
AB  - The purpose of this study was to improve the visualization of long-axis black
      blood imaging of the carotid arteries. We experimented on phantom and in-vivo
      study of 3 dimension (3D) inversion recovery T(1) turbo field echo combined with
      phase sensitive inversion recovery (PSIR-3D IR-T(1)TFE) at 3.0 Tesla. As a
      result, the contrast has been improved by calculated images of PSIR-3D IR-T(1)TFE
      set to inversion time (TI) 350 ms that is shorter than null point of blood. This
      displays that the contrast between blood and tissues can be improved when the
      longitudinal magnetization of blood is a negative. Therefore, the visualization
      of long-axis black-blood imaging of the carotid arteries has been improved by the
      calculated images of PSIR-3D IR-T(1)TFE set to TI that is shorter than null point
      of blood.

PMID- 21869543
TI  - [An investigative report concerning safety and management in the magnetic
      resonance environment: there are more accidents than expected].
AB  - Using a questionnaire, we surveyed 2,500 facilities in Japan to clarify medical
      accidents concerning the magnetic resonance device and its environment. Data
      derived from 1,319 valid responses (52.8%), allowed us to analyze the situation
      of (or the reason for) the occurrence of the accidents and their environmental
      factors. Five hundred and nine facilities (39% of all facilities) had the
      experience of magnetically induced displacement of the large ferromagnetic
      material. Intravenous (I.V.) drip stands were involved the largest number of
      them: 31% (228 cases). Oxygen bottles had the second largest number of incidents:
      20%. There were also many incidents involving various materials brought in by non
      medical staff (e.g. stepladder for construction). About 20% of the accidents
      occurred outside of working hours. Patients in 12% of the facilities (154
      facilities) experienced burns. In 39 of the cases, burns were received to the
      inside of the thighs. In 38 of the cases, patients received burns from an
      electrical cable touching the skin. There were also frequent incidents of burning
      regarding the boa. We received reports of burns and pain from the halo vest even
      though it's required to be worn for MR safety. Regarding incidents of
      contraindications, 280 patients with pacemakers were brought into the magnetic
      resonance (MR) inspection room. Twelve percent of the facilities experienced
      natural quench. Lack of training for the staff who introduce and operate high
      magnetic field devices are considered involving frequently occurring accidents of
      attractions and burns at hospitals with over 500 beds caused by carrying in
      materials.

PMID- 21869544
TI  - [Image quality assessment of Step&Shoot overlap reconstruction (SSOR) for cardiac
      computed tomography (CT)].
AB  - BACKGROUND: Step&Shoot cardiac computed tomography (CT) provides the benefit of
      significant reduction in radiation dose compared to helical cardiac CT
      acquisitions. We think that a difference occurs in image quality by presence of
      overlap reconstruction (fractionated sentence, attempted to clarify). PURPOSE: We
      studied the utility of Step&Shoot overlap reconstruction (SSOR). METHODS: We
      evaluated image quality of SSOR by comparing z-axis spatial resolution on various
      s in scanners that SSOR is possible and for those that are impossible. RESULTS:
      SSOR indicated better z-axis spatial resolution and less variation over the field
      of view (FOV) (in z & x-y directions) as compared with Step&Shoot without overlap
      reconstruction (SS). In addition, SS showed inadequate image reproducibility due
      to aliasing error in z-direction (lack of sampling interval). CONCLUSIONS: SSOR
      would contribute to improvement of the image quality of Step&Shoot cardiac CT.

PMID- 21869545
TI  - [Effective method for decontaminating radioactive X-ray detectors (imaging
      plates)].
AB  - Several hospitals have been observing black spots in medical images, and the
      radioisotopes (RIs) that cause the spots needs to be removed from the X-ray
      receptors. Our purpose is to show a flowchart for finding out under which
      conditions an imaging plate (IP) and other parts (for example, the cassette) are
      contaminated by RIs and to propose an effective method to remove them. The
      procedure follows. (1) Is RI activity low? (2) Are the surfaces of other parts
      contaminated? (3) Is the surface of the IP contaminated? (4) Are the insides of
      the other parts contaminated? To remove the adhered RIs, we applied a wipe test
      method using a wet type of chemical wiper. A certain hospital that observed black
      spots experimented with this method. As a result, the contaminated condition of
      the X-ray receptor was identified. In addition, we were able to remove the RIs
      from the IP. Therefore, our procedure is very effective for decontaminating
      adhered RIs from receptors.

PMID- 21869546
TI  - [Past and present of medical exposure measurement].

PMID- 21869547
TI  - [3. A method of the radiation exposure dosimetry by the X-ray photography].

PMID- 21869548
TI  - [Quality assurance for high dose rate brachytherapy equipment - practice and
      agenda - ].

PMID- 21869549
TI  - [3. Kitasato University].

PMID- 21869550
TI  - [Report on RSNA2010].

PMID- 21869551
TI  - [Survey of states of introduction and safety assurance of medical systems etc. in
      the 2010 fiscal year: part 2].

PMID- 21869553
TI  - Immunocytochemical analysis of a three-dimensional spheroidal culture system.

PMID- 21869554
TI  - Characteristics of the electrophysiological activity of muscles attached to the
      transverse carpal ligament in carpal tunnel syndrome.
AB  - The main cause of carpal tunnel syndrome (CTS) remains unknown. Stiffness of the
      subcutaneous area of the volar aspect of the carpal tunnel is present in many
      patients and suggests that the stiffness of muscles attached to the transverse
      carpal ligament is increased. We performed an electrophysiological study to
      investigate muscle activities and to clarify whether the stiffness of muscles
      attached to the transverse carpal ligament is involved in the pathogenesis of
      CTS. The subjects of this study included 16 patients with early CTS showing no
      motor dysfunction. Both thenar muscles (opponens pollicis, abductor pollicis
      brevis, and flexor pollicis brevis) and hypothenar muscles (opponens digiti
      minimi, abductor digiti minimi, flexor digiti minimi brevis) were investigated.
      Surface electrodes were placed on each muscle, and maximum voluntary contractions
      with the thumb and little finger in opposition were maintained for 3 seconds in
      all patients and in 7 control subjects. Electromyographs were subjected to fast
      Fourier transform analysis, and the root mean square (RMS) and the mean power
      frequency (MPF) were determined for each muscle. The RMS of the opponens pollicis
      was significantly less in hands affected by CTS (292.8 uV) than in healthy hands
      (405.9 uV). The RMS did not differ between affected hands and healthy hands for
      the other 2 thenar muscles but did differ significantly for the hypothenar
      muscles. The MPF did not differ between affected hands and healthy hands for any
      muscle. The results show that electrophysiological differences are present among
      muscles innervated by the median nerve and that hypothenar muscles originally
      unrelated to median nerve dysfunction are also affected in early CTS. These
      results suggest that modulation of muscles attached to the transverse carpal
      ligament is involved in the pathogenesis of CTS.

PMID- 21869555
TI  - The performance evaluation of endotoxin retentive filters in haemodialysis.
AB  - BACKGROUND: Hemodialysis is a method for removing uremic toxins and water
      directly from the blood into a dialysis fluid through an artificial semipermeable
      membrane called a dialyzer. The ability of the dialyzer to remove uremic toxins
      has steadily improved, but the likelihood has also increased that bioactive
      substances, such as bacterial endotoxin (ET) fragments, can be transferred from
      the dialysis fluid into the patient's blood through the phenomena of back
      diffusion and back-filtration in the dialyzer. Therefore, further efforts to
      improve the quality of water are required. In 2008, the Committee of Scientific
      Academy of the Japanese Society for Dialysis Therapy presented its new
      recommendations for the quality standards of dialysis fluid, but achieving and
      maintaining these standard values would seem difficult without installing an ET
      retentive filter (ETRF). In the present study, we evaluated whether the standards
      for ultrapure dialysis fluid of the Japanese Society for Dialysis Therapy can be
      achieved and maintained by installing 3 types of ETRF for a period of 12 months.
      METHODS: To evaluate the quality of dialysis fluid, ET values were measured with
      nephelometry, and viable cell counts were determined with the membrane filter
      method. Changes in the basic performance of the ETRFs were evaluated by measuring
      their water permeability, ET-retentive capacity, and hollow-fiber membrane
      intensity. Moreover, the hollow-fiber membrane surfaces of the ETRFs were
      observed with scanning electron microscopy, and the elements of the adherent
      substances were identified by means of energy dispersive X-ray spectrometry.
      RESULTS: The ET concentrations were less than the limit of detection during the
      evaluation period for samples obtained at post-ETRF sites. The viable cell counts
      for pre-ETRF sites were approximately 10 colony-forming units/mL. However,
      colonies had not formed in samples obtained from the post-ETRF sites. The
      substances adhering to hollow fibers included the silicon from the dialysate
      powder, the iron from the fluid path, and the elements derived from stainless
      steel. Scanning electron microscopy of the ETRF hollow fibers showed no
      substances except the hollow fibers and the elements derived from the dialysis
      fluid. CONCLUSION: Installation of an ETRF is useful for achieving and
      maintaining the quality standards for ultrapure dialysis fluid and for preventing
      the entry into the blood of ETs, viable cells, and such substances as silicon and
      metals.

PMID- 21869556
TI  - Localization of cytochrome P4502E1 enzyme in normal and cancerous gastric mucosa
      and association with its genetic polymorphism in unoperated and remnant stomach.
AB  - BACKGROUND: Exposure to nitroso compounds and the activity of cytochrome P450 2E1
      (CYP2E1), an activation enzyme for these carcinogens, are important factors in
      gastric carcinogenesis. Here, we investigated the potential correlation between
      genetic variation in CYP2E1 and its enzyme expression as detected with
      immunohistochemical (IHC) staining and cancer susceptibility in unoperated and
      remnant stomach. METHODS: Expression of CYP2E1 in the stomach (n=117) was
      detected with IHC staining using a polyclonal anti-CYP2E1 antibody.
      Interindividual variation in CYP2E1 enzyme activity was then compared with
      genetic polymorphisms in the transcriptional flanking region of the CYP2E1 gene
      by restriction fragment length polymorphism (RFLP) detection using the Rsa I
      restriction enzyme. Genetic polymorphisms of Rsa I RFLP in CYP2E1 were
      investigated in 499 patients with gastric cancer (466 unoperated stomachs and 33
      remnant stomachs) and 553 control patients with benign gastroduodenal diseases.
      RESULTS: Mucosal IHC staining for CYP2E1 was stronger in areas of intestinal
      metaplasia, particularly in endocrine cells, which stained consistently and
      strongly. Expression of CYP2E1 enzyme in areas of IHC staining were confirmed
      with Western blot analysis and showed a significant association between the
      degree of staining and the CYP2E1 genotype (p<0.01) in cancer tissues and in the
      foveolar epithelium of normal gastric mucosa. No association between specific
      CYP2E1 genotype and gastric cancer risk in the unoperated stomach was found in
      either the large study or the age- and gender-matched case-control study.
      However, the frequency of rare alleles (C1/C2 or C2/C2) was significantly higher
      in patients with cancer in the remnant stomach following gastrectomy than in
      controls subjects without cancer (odds ratio=2.8, 95% confidence interval=1.3
      5.8) or those with primary gastric cancer (odds ratio=2.6, 95% confidence
      interval=1.3-5.5). CONCLUSIONS: CYP2E1 genetic polymorphisms might correlate with
      CYP2E1 enzyme expression levels in normal and cancerous gastric tissues. These
      polymorphisms do not influence the development of primary stomach cancer but may
      do so in specific conditions, such as the remnant stomach after gastrectomy.

PMID- 21869557
TI  - Evaluation of laparoendoscopic single-site gynecologic surgery with a multitrocar
      access system.
AB  - OBJECTS: Laparoendoscopic single-site surgery (LESS) is an ideal approach for
      gynecologic surgery and yields better cosmetic results. However, a standard
      umbilical approach with LESS is not appropriate for gynecologic surgery requiring
      intra-abdominal suturing and dissection requiring traction. Therefore, we have
      developed a new multitrocar access system for gynecologic LESS. The purpose of
      this study was to evaluate the efficacy of gynecologic LESS using this access
      system. METHODS: This access system consists of one 12-mm trocar, two 5-mm
      trocars, and a 5-mm flexible laparoscope. Two 5-mm trocars with small port heads
      were inserted cross-wise on opposite sides of the sleeve of the centrally
      positioned 12-mm trocar to maintain triangulation. Thirty-eight patients with
      various gynecologic conditions underwent LESS with this access system. The
      results of these surgeries were retrospectively compared to those of conventional
      laparoscopic procedures. RESULTS: Of the 38 LESS procedures performed with this
      access system, none was up-converted, converted to an open laparotomy, or
      required blood transfusion. The Salpingo-oophorectomy with LESS had several
      benefits, such as no extension of the skin incision of the trocar site and no
      leakage of the contents of the ovarian cyst into the peritoneal cavity, over that
      with conventional laparoscopy. A comparison of LESS (11 patients) and
      conventional laparoscopy (16 patients) for total hysterectomy showed no
      significant difference in total blood loss (234.0 mL vs. 221.6 mL) or the weight
      of the resected uterus (276.0 g vs. 285.0 g), although the mean total operative
      time was greater with LESS (199.0 min vs. 168.5 min). CONCLUSION: Our multitrocar
      access system is safe and secure, and can be adapted for various gynecologic
      surgeries involving complicated procedures. LESS with this access system achieves
      results comparable to those of conventional laparoscopy with 4 ports, although
      the operative time is longer.

PMID- 21869558
TI  - Conservative management of hyperreactio luteinalis: a case report.
AB  - Hyperreactio luteinalis (HL) is characterized by bilaterally enlarged ovaries
      containing multiple self-limited theca lutein cysts and is usually associated
      with increased production of human chorionic gonadotropin in the presence of
      trophoblastic disease or multiple pregnancies. About 30 cases of HL have been
      reported in patients with normal singleton pregnancies, and most of these
      patients required surgical intervention during their first pregnancy because of
      ovarian torsion or to rule out of ovarian malignancy. However, the accurate
      diagnosis of HL by means of laboratory tests and magnetic resonance imaging and
      the exclusion of ovarian malignancy in asymptomatic pregnant woman may avoid
      unnecessary surgical intervention or termination of pregnancy. The present report
      describes case of HL in a woman with a normal singleton pregnancy in whom
      conservative management allowed the preservation of both ovaries.

PMID- 21869559
TI  - Malignant hepatic epithelioid hemangioendothelioma with abdominal pain due to
      rapid progression.
AB  - Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor. We report on a
      patient who underwent hepatectomy for malignant HEH associated with abdominal
      pain due to rapid progression. An 83-year-old man was admitted to Nippon Medical
      School Hospital because of acute, severe upper abdominal pain. Seven months
      before admission, a hepatic tumor, 3 cm in diameter, had been detected in the
      left lateral sector. The diagnosis was hepatic cavernous hemangioma. Abdominal
      ultrasonography revealed a heterogeneous hyperechoic tumor with a smooth border,
      6 cm in diameter, in the left lateral sector (segment 3). Contrast-enhanced
      computed tomography of the abdomen showed that the tumor was enhanced from the
      early to the late phase. Abdominal angiography revealed a cotton wool-like
      appearance of the tumor. The diagnosis was hepatic cavernous hemangioma. A
      malignancy could not be ruled out because of the tumor's rapid growth, which had
      caused abdominal pain. Left hepatectomy was performed. Histopathological
      examination showed necrosis throughout the tumor. Slightly pleomorphic neoplastic
      cells with rounded, spindle-like nuclei and scant cytoplasm were sporadically
      found in vascular channels. Intracytoplasmic lumina occasionally contained red
      cells. Neoplastic cells were positive for factor VIII-related antigen, CD31, and
      CD34. The Mib-1 index was high. The tumor was diagnosed as malignant HEH. The
      postsurgical course was uneventful, and the patient was discharged on
      postoperative day 11. After 3 months, multiple metastatic tumors appeared in
      right hepatic lobe. Transcatheter arterial chemoembolization was performed.

PMID- 21869560
TI  - A patient with idiopathic cholesterol crystal embolization: effectiveness of
      early detection and treatment.
AB  - A 72-year-old man was admitted to our hospital because of progressive renal
      dysfunction persisting for 1.5 months. Physical examination showed livedo
      reticularis of the toes of both feet, peripheral edema, and gait disturbance due
      to the toe pain. The levels of blood urea nitrogen (50.0 mg/dL) and creatinine
      (2.81 mg/dL) were elevated, and eosinophilia (10%, 870/uL) was noted. A biopsy of
      the area of livedo reticularis revealed cholesterin crystals. The patient had not
      undergone angiography, anticoagulation therapy, or antithrombotic treatment.
      Idiopathic cholesterol crystal embolization was diagnosed. Transesophageal
      echocardiography revealed intimal thickening of the aorta and plaque. Oral
      steroid therapy was started because of the progressive renal dysfunction. After
      steroid therapy, the symptoms improved. Early diagnosis and treatment are
      important. Renal dysfunction is a common symptom in elderly patients. Cholesterol
      crystal embolization should also be considered as a cause of unexplained renal
      dysfunction, especially in such patients.

PMID- 21869561
TI  - Unexplained lower abdominal pain associated with sacroiliac joint dysfunction:
      report of 2 cases.
AB  - A 25-year-old woman and a 31-year-old man presented with chronic lower back pain
      and unexplained lower abdominal pain. Both patients had groin tenderness at the
      medial border of the anterior superior iliac spine. The results of radiographical
      and physical examinations suggested sacroiliac joint dysfunction. Sacroiliac
      joint injection relieved their symptoms, including groin tenderness. In our
      experience, groin tenderness is highly specific for sacroiliac joint dysfunction.
      We speculate that spasm of the iliac muscle can cause groin pain and tenderness.
      Groin pain and a history of unexplained abdominal pain, with lower back pain, are
      symptoms that suggest sacroiliac joint dysfunction. Additionally, compression of
      the iliac muscle is a simple and useful maneuver; therefore, it can be used as a
      screening test for sacroiliac joint dysfunction, alongside other provocation
      tests.

PMID- 21869562
TI  - Three cases of carcinoma of the hypopharynx developing as metachronous second
      primary cancers after total laryngectomy with radiotherapy for carcinoma of the
      larynx.
AB  - We describe 3 cases of metachronous hypopharyngeal cancer developing after
      laryngeal cancer had been treated with both radiotherapy and total laryngectomy.
      All 3 patients were men, 2 were 89 years old, and 1 was 65 years old. All
      patients had undergone total laryngectomy and radiotherapy for cancer for the
      glottis more than 20 years earlier. All patients underwent total
      hypopharyngectomy with jejunal free flap reconstruction. Surgery was complicated
      by scars from previous cancer treatment, and highly sophisticated surgical skills
      are needed, especially for preparing the recipient vessels. The postoperative
      period was largely uneventful and without fatal complications, however, 2 of the
      3 patients died of distant metastasis 22 months and 31 months after surgery.

PMID- 21869563
TI  - The hospitalization assistance policy system in Japan.
AB  - In Japan, the hospitalization assistance policy (HAP) system helps pregnant women
      who, for financial reasons, cannot give birth at medical institutions. The HAP
      system allows these women to deliver at specified midwifery institutions. We
      compared women with singleton pregnancies who gave birth with the HAP system
      (n=150) or without (control; n=2,869) . Although the percentage of women younger
      than 20 years was significantly greater in the HAP system group than in the
      control group, the parity number in the HAP system group was significantly
      greater than that in the control group. The percentage of non-Japanese was
      significantly higher in the HAP system group than in the control. The rates of
      preterm delivery and of low birth weight (<2,000 g) were significantly greater in
      the HAP system group than in the control group. From the perspective of perinatal
      medicine, social risks, such as poverty, present some perinatal problems, even in
      Japan.

PMID- 21869564
TI  - Inhibitory effect of chlorpromazine on RANKL-induced osteoclastogenesis in mouse
      bone marrow cells.
AB  - Chlorpromazine (CPZ), the first widely used phenothiazine tranquilizer, is shown
      to inhibit the action of intracellular calmodulin (CaM) and bone resorption in
      vivo and in vitro. In this study, CPZ (0.63 - 10 uM) dose-dependently inhibited
      the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive
      osteoclast-like cells in mouse bone marrow cells (BMCs) treated with
      1alpha,25(OH)(2)D(3) (10 nM) or soluble receptor activator of nuclear factor
      kappaB ligand (s-RANKL) (20 ng/ml). Expressions of mRNA for the nuclear factor of
      activated T-cells c1 (NFATc1), a key regulator of osteoclast differentiation;
      dendritic cell-specific transmembrane protein (DC-STAMP), an essential protein
      for cell-cell fusion; and characteristic markers of osteoclasts such as TRAP,
      cathepsin K, carbonic anhydrase II, and calcitonin receptor in BMCs were up
      regulated by s-RANKL and decreased by the addition of CPZ (5 uM) or the selective
      CaM antagonist W7, but not the inactive analog W5. The general CaM kinase (CaMK)
      inhibitor KN-93 and CaM-dependent phosphatase calcineurin inhibitor FK-506 also
      inhibited s-RANKL-induced osteoclastogenesis. Phenothiazines such as CPZ,
      trifluoperazine (TFPZ), and promethazine (PMZ) inhibited s-RANKL-induced
      osteoclast-like cell formation in mouse BMCs. Osteoclastogenesis inhibitory
      effects decreased in the order of TFPZ, CPZ, PMZ, depending on their anti-CaM
      potency. These findings suggest that CPZ inhibits RANKL-induced
      osteoclastogenesis by its anti-CaM action.

PMID- 21869565
TI  - Protective effect of neurotrophic agent T-817MA against inner ear barotrauma in
      the guinea pig.
AB  - T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), a
      neurotrophic compound newly synthesized for the treatment of Alzheimer's disease,
      has been found to reduce oxidative stress and exert neuroprotective effects. By
      assessing the auditory functioning and observing the cochlear sensory epithelia,
      we investigated whether T-817MA protects the cochlea from inner ear barotrauma in
      guinea pigs treated with rapidly intense pressure change. Sustained oral
      administration of T-817MA significantly reduced the extent of auditory threshold
      shifts and outer hair cell loss, indicating that T-817MA attenuates the intense
      pressure-induced cochlear damage that accompanies inner ear barotrauma via
      antioxidative activity.

PMID- 21869566
TI  - Inactivation of membrane surface ecto-5'-nucleotidase by sodium nitroprusside in
      C6 glioma cells.
AB  - Ecto-5'-nucleotidase (NT5E), a predominant enzyme that produces extracellular
      adenosine from AMP, plays an important role in a variety of physiological and
      pathophysiological processes. This study was performed to identify agents that
      affect NT5E activity using C6 glioma cells. When cells were incubated with sodium
      nitroprusside (SNP), phorbol 12-myristate 13-acetate, forskolin,
      lipopolysaccharide, or interferon-gamma, only SNP inhibited NT5E activity in a
      time- and concentration-dependent manner (IC(50) = 1.2 uM). The inhibitory effect
      of SNP was long-lasting even after SNP washout; and its action was not mimicked
      by nitric oxide generating agents, 8-bromo cyclic GMP, ferricyanide,
      ferrocyanide, or sodium cyanide. SNP did not change NT5E mRNA level or membrane
      surface protein expression. Similar to SNP, Fe(2+) inhibited NT5E activity, but
      to a lesser extent. Although Fe(2+) is known to increase oxidative stress, Fe(2+)
      mediated oxidative stress was not involved in SNP inhibition of NT5E because the
      inhibition of NT5E by SNP was not affected by superoxide dismutase and catalase.
      In contrast, addition of Zn(2+), an essential metal co-factor of NT5E activity,
      prevented SNP from inhibiting NT5E. These results suggest that SNP disrupts a
      critical Zn(2+)-dependent enzyme activity and might be useful as a
      pharmacological tool for inhibiting NT5E.

PMID- 21869567
TI  - Detection of spatial and temporal influences on bacterial communities in an urban
      stream by automated ribosomal intergenic ribosomal spacer analysis.
AB  - The Yarqon is the largest urban river in Israel, and is a slow-flowing stream
      whose water originates mostly from wastewater treatment plants. Thus, its
      microbial community is expected to be heavily impacted both by anthropogenic
      factors and by seasonal temporal variation. In order to identify the main factors
      that influence the bacterial community, and their spatial-temporal variation, 50
      samples were collected representing five different time points and eleven
      locations. Samples were analyzed for biotic and a-biotic parameters and the
      bacterial populations were analyzed by Automated Ribosomal Intergenic Spacer
      Analysis (ARISA). Bacterial richness and diversity were calculated and compared
      across samples. Canonical Correspondence Analysis (CCA) showed that ARISA
      clustered the samples according to temporal variation. Molecular fingerprinting
      analysis provided a snapshot of the microbial community and showed good
      correlation with geochemical parameters, despite the rapid changes of the
      Mediterranean environment and the anthropogenic impact. Molecular fingerprinting
      methods based on natural fragment length polymorphisms may therefore represent a
      supplementary approach for stream monitoring, alongside physico-chemical
      measurements.

PMID- 21869568
TI  - Reducing sugar-producing bacteria from guts of Tenebrio molitor Linnaeus (yellow
      mealworm) for lignocellulosic waste minimization.
AB  - The guts of Tenebrio Molitor Linnaeus (yellow mealworm) were used as inocula to
      isolate reducing sugar-producing bacteria during bioconversion of lignocellulose
      to reducing sugars in this study. Three carbon sources, i.e., carboxymethyl
      cellulose (CMC), filter paper (FP), and lignocellulosic waste (LIG), were
      specifically selected; and two types of culturing media (M1 and M2) were used.
      After 6 months of sequential cultivation, lignocellulose (i.e., polysaccharides)
      degradation of enrichments M1-CMC (47.5%), M1-FP (73.3%), M1-LIG (70.4%), M2-CMC
      (55.7%), M2-FP (73.1%) and M2-LIG (71.7%) was achieved, respectively, with
      incubation for 48 h. Furthermore, seven bacterial strains were successfully
      isolated corresponding to most of the major bands detected by denaturing gradient
      gel electrophoresis analysis. The maximum reducing sugars yield by the
      combination of Agromyces sp. C42 and Stenotrophomonas sp. A10b was 56.7 mg g.LIG(
      1) of 48 h, which is approximate 2-5 times higher than the original enrichments
      and individual microbial strains. These findings suggest that bioconversion by
      microorganisms from mealworm guts has great application potential for
      lignocellulose hydrolysis.

PMID- 21869569
TI  - Changes in the acetogenic population in a mesophilic anaerobic digester in
      response to increasing ammonia concentration.
AB  - Changes in the acetogenic population were investigated in an experimental
      laboratory-scale biogas reactor (37 degrees C) subjected to gradually elevated
      ammonia levels (0.8 to 6.9 g NH(4)(+)-N L(-1)). A shift from aceticlastic acetate
      degradation to syntrophic acetate oxidation had previously been confirmed in this
      reactor. In a parallel control reactor, operating at constant ammonia levels
      (0.65-0.90 g NH(4)(+)-N L(-1)), acetate degradation proceeded via the
      aceticlastic pathway throughout the operating period (660 d). The acetogenic
      populations in the reactors were analysed using degenerated primers designed to
      target the functional gene encoding a key enzyme of the acetyl-CoA pathway, 10
      formyltetrahydrofolate synthetase (FTHFS). The analysis consisted of terminal
      restriction fragment length polymorphism (T-RFLP) analysis coupled with the
      construction of clone libraries, and quantitative PCR (qPCR) analysis. The T-RFLP
      data obtained were statistically analysed by non-metric multidimensional scaling.
      The most abundant FTHFS genes recovered in the clone libraries were assigned to
      terminal restriction fragments of the T-RFLP profile. The results of the
      investigation clearly indicated that increased ammonia concentration
      substantially influenced the putative acetogenic population structure and caused
      two distinct shifts of the most abundant members; however, the identity of the
      dominating species remains unknown, as none of the genes had been identified
      previously. Despite the shifts in the population, the qPCR analysis revealed a
      relatively stable abundance of the acetogenic population throughout the
      operation.

PMID- 21869570
TI  - Parathyroid hormone (1-34) improves bone mineral density and glucose metabolism
      in Spontaneously Diabetic Torii-Lepr(fa) rats.
AB  - The Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat, a model of obese type
      2 diabetes, shows obesity, hyperglycaemia and low bone mineral density (BMD). The
      objective of this study is to evaluate the effects of parathyroid hormone (1-34)
      [PTH(1-34)] on BMD and glucose metabolism in the SDT-fa/fa rat. SDT-fa/fa rats
      showed obesity with hyperglycaemia and decreased serum osteocalcin levels and the
      tibial BMD. A 4-week treatment of PTH(1-34) (20 ug/kg/day) increased the serum
      osteocalcin levels and the tibial BMD, and decreased the serum glucose levels
      without changing the serum insulin levels. These findings indicate that PTH(1-34)
      improved not only BMD but also glucose metabolism in SDT-fa/fa rats. This study
      suggests that PTH(1-34) is a novel agent for the treatment of diabetic
      osteoporosis.

PMID- 21869571
TI  - A clinical case of severe anemia in a sheep coinfected with Mycoplasma ovis and
      'Candidatus Mycoplasma haemovis' in Hokkaido, Japan.
AB  - A 2-year-old East Friesian sheep imported from Australia exhibited severe anemia
      after contagious pustular dermatitis in Hokkaido, Japan. Hemoplasma infection was
      confirmed in blood smears. Both Mycoplasma ovis and 'Candidatus Mycoplasma
      haemovis' were detected by PCR and sequence analyses. In the epidemiological
      analysis, dual pathogens were detected in 6 of 12 (50.0%) sheep imported from
      Australia with the infected ewe at the same time, 1 of 5 (20.0%) sheep introduced
      from a domestic farm in Hokkaido, and in 1 of 16 (6.3%) sheep from an
      epidemiologically unrelated ranch. It is the first clinical case of sheep to
      confirm coinfection of these pathogens in Japan.

PMID- 21869572
TI  - Expression of ADAMTS-7 and ADAMTS-12 in the nucleus pulposus during degeneration
      of rat caudal intervetebral disc.
AB  - Earlier reports have shown that ADAMTS-7 and ADAMTS-12 (a disintegrin and
      metalloproteinase with thrombospondin motifs) can bind to and degrade COMP
      (cartilage oligomeric matrix protein) in cartilage. However, the expression of
      ADAMTS-7 AND ADAMSTS-12 in both normal intervertebral discs and degenerative
      intervertebral discs (IVDs) is still unknown and the changes that occur in the
      degenerating intervertebral disc remain to be determined. The aim of this study
      was to explore the expression and role of the ADAMTS in the degenerative process
      of the intervertebral disc. Rat caudal discs were loaded at 1.3 MPa in vivo with
      an external compression device. The discs were loaded for one week, and and the
      nuclei pulposi (NPs) were harvested to investigate cell apoptosis and expression
      of collagen II and aggrecan for confirmation of disc degeneration. The changes of
      ADAMTS-7 and ADAMTS-12 and COMP were recorded during one week of loading. A
      second group of rats receiving no load were used as controls. After one week of
      loading, the NPs suffered degenerative changes as reflected by decreases in cell
      viability, collagen II, and aggrecan. Dramatic increases in expression of ADAMTS
      7 and ADAMTS-12 and COMP fragment were detected after 18 hr of loading; however,
      this was accompanied by a sharp decrease of COMP expression. These changes were
      not observed in the control group. The significant increase in COMP possibly
      suggests a favorable role of COMP in preventing loading and degeneration of
      matrix; however, this positive effect might be diminished by ADAMTS-7 and ADAMTS
      12, whose augmentation were dramatic during disc degeneration.

PMID- 21869573
TI  - Change in antimicrobial resistance pattern in Salmonella enterica serovar
      Typhimurium isolates detected in a beef cattle farm.
AB  - Multidrug-resistant Salmonella enterica serovar Typhimurium (S. Typhimurium)
      isolates with four different antimicrobial resistance patterns obtained from a
      beef cattle farm were characterized to determine their clonality.
      Macrorestriction analysis of genomic DNA revealed that these four isolates are
      closely related to each other and can be classified as a newly emerged pulsed
      field gel electrophoresis type among cattle: cluster VII. Three of the four
      isolates showed resistance to extended-spectrum cephalosporins (ESCs), and this
      resistance was mediated by AmpC beta-lactamase encoded by the bla(CMY-2) gene in
      a 190-kbp IncA/C plasmid. Results of restriction analysis and IncA/C backbone PCR
      suggest that the three 190-kbp plasmids are identical and that a 70-kbp IncA/C
      plasmid of the ESC-susceptible isolate is derived from the 190-kbp plasmid by a
      deletion event. Three isolates harboured a virulence-resistance plasmid (165 or
      180 kbp), and restriction analysis revealed that these plasmids were identical or
      closely related to each other. These results suggest that the four S. Typhimurium
      cluster VII isolates originate from a common ancestor that probably invaded the
      farm prior to the salmonellosis outbreak. Antimicrobial resistance patterns may
      not necessarily reflect the relationships of the isolates.

PMID- 21869574
TI  - Significance of differences between brain temperature and core temperature (delta
      T) during mild hypothermia in patients with diffuse axonal injury.
AB  - The differences between brain and bladder temperature (delta T), and the
      relationship of delta T to cerebral perfusion pressure (CPP) and jugular venous
      oxygen saturation (SjO(2)) were studied during hypothermia in 11 patients with
      severe traumatic brain injury, of whom 5 underwent conservative treatment for
      diffuse axonal injury (DAI) (DAI group) and 6 who underwent decompressive
      craniectomy for hematoma (SDH group). All patients underwent hypothermia
      treatment. Brain temperature was monitored via an intraparenchymal catheter.
      Bladder temperature was used as the core temperature. SjO(2) was measured
      continuously. The outcome of all patients was evaluated at discharge using the
      Glasgow Outcome Scale. Delta T in the SDH group was significantly lower than that
      in the DAI group. No relationship was found between delta T and CPP during the
      investigation period. A significant correlation between delta T and SjO(2) was
      seen in the DAI group, but not in the SDH group. Decompressive craniectomy
      affects the brain temperature through external environmental factors. Measurement
      of brain temperature may be a reliable indicator of cerebral blood flow and brain
      metabolism in patients with DAI and closed cranium during hypothermia. Further
      experience is required to test this proposal.

PMID- 21869575
TI  - Incidence of hemodynamic depression after carotid artery stenting using different
      self-expandable stent types.
AB  - The rates of hemodynamic depression (HD) and thromboembolism were compared in 95
      carotid artery stenting (CAS) procedures performed in 87 patients with severe
      carotid artery stenosis using self-expandable braided Elgiloy stents (Wallstent)
      in 52 and slotted-tube Nitinol stents (Precise) in 43 procedures. The blood
      pressure, pulse rate, and neurological signs were recorded at short intervals
      during and after CAS. All patients underwent diffusion-weighted magnetic
      resonance imaging within 5 days after the procedure. The incidences of
      hypotension, bradycardia, and both were 17.9%, 3.2%, and 11.6%, respectively. The
      rate of postprocedural HD was 23.1% with Wallstent and 44.2% with Precise; the
      difference was significant (p = 0.025). No patient manifested major
      cardiovascular disease after CAS. Diffusion-weighted magnetic resonance imaging
      revealed thromboembolism after 26.9% and 34.9% of Wallstent and Precise stent
      placement procedures, respectively; the difference was not significant. The type
      of self-expandable stent placed may affect the risk of procedural HD in patients
      undergoing CAS. Postprocedural HD was resolved successfully by the administration
      of vasopressors and by withholding antihypertensive agents.

PMID- 21869576
TI  - Intramedullary cavernous angiomas of the spinal cord: clinical characteristics of
      13 lesions.
AB  - Magnetic resonance imaging has increased the incidence of the diagnosis of
      intramedullary cavernous angioma. Surgical therapy tends not to be recommended
      for asymptomatic lesions, but symptomatic lesions that bleed recurrently should
      be treated. The natural course of intramedullary cavernous angioma remains
      unknown and arguments have been raised against the surgical treatment of
      symptomatic lesions. We reviewed the clinical features of 13 intramedullary
      cavernous angiomas in 12 patients surgically treated between 1988 and 2009. The 7
      men and 5 women were aged from 14 to 60 years, the preoperative interval ranged
      from 0 to 161 months, and the mean number of hemorrhages in the 13 lesions was
      2.5. Sixteen operations were performed to treat the 13 lesions. The surgical
      approach depended on the lesion location. The outcome of patients with mild to
      moderate preoperative symptoms (McCormick grades I-III) was significantly better
      than that of patients with severe symptoms (McCormick grade IV) (p < 0.05).
      Symptomatic intramedullary cavernous angioma tends to bleed repeatedly. The
      lesion should be surgically removed to avoid further deterioration due to
      recurrent hemorrhages. The shortest path approach should be selected based on
      preoperative images and complete removal should be attempted. Residual lesion may
      be masked by surrounding gliosis, so careful postoperative follow up is
      necessary.

PMID- 21869577
TI  - Modified three-dimensional brain model for study of the trans-sylvian approach.
AB  - The trans-sylvian approach is one of the most frequently employed neurosurgical
      procedures, but it is difficult for medical students to understand the approach
      stereoscopically. A three-dimensional model equipped with an arachnoid membrane
      and sylvian vein was developed which can be repeatedly used to simulate surgery
      for the education of medical students and residents in the trans-sylvian
      approach. The model was prepared using existing models of the skull bone, brain,
      and cerebral artery. Polyvinylidene chloride film, commonly used as plastic wrap
      for food, was adopted for the arachnoid membrane, and wetted water-insoluble
      tissue paper for the arachnoid trabeculae. The sylvian vein was prepared by
      ligating woolen yarn with cotton lace thread at several sites. Students and
      residents performed the trans-sylvian approach under a microscope, and answered a
      questionnaire survey. Using this model, simulation of division of the arachnoid
      membrane and arachnoid trabeculae, and dissection of the sylvian vein was
      possible. In the questionnaire, the subjects answered 8 questions concerning
      understanding of the stereoscopic anatomy of the sylvian fissure, usefulness of
      the simulation, and interest in neurosurgical operation using the following
      ratings: yes, very much; yes; somewhat; not very much; or not at all. All items
      rated as 'yes, very much' and 'yes' accounted for more than 70% of answers. This
      model was useful for medical students to learn the trans-sylvian approach. In
      addition, repeated practice is possible using cheap materials, which is
      advantageous for an educational model.

PMID- 21869578
TI  - Coil embolization of a traumatic intracranial aneurysm of the distal part of the
      azygos anterior cerebral artery followed up for 4 years.
AB  - Traumatic intracranial aneurysms are rare, usually occur as a result of traffic
      accidents, and are associated with high rates of morbidity and mortality. A 12
      year-old boy was admitted for treatment of cerebral hemorrhage in the left
      frontal lobe, 3 months after a traffic accident. Angiography revealed an
      intracranial aneurysm of the distal part of the azygos anterior cerebral artery
      (ACA). The maximum size of this aneurysm was 9.5 mm. Coil embolization was
      successfully performed with preservation of the parent arteries. Angiography
      performed at the 4-year follow-up examination revealed no abnormalities. The
      present case showed that primary coiling may allow aneurysm occlusion along with
      parent vessel preservation in selected cases of traumatic intracranial aneurysm
      of the distal part of the azygos ACA.

PMID- 21869579
TI  - Basi-parallel anatomical scanning magnetic resonance imaging in patients with
      bilateral vertebrobasilar artery dissections.
AB  - A 31-year-old man presented with bilateral unruptured vertebral artery (VA)
      dissections. The temporal course of the dissected arteries was successively
      evaluated using brain surface imaging modality basi-parallel anatomical scanning
      (BPAS) magnetic resonance (MR) imaging in combination with the conventional
      modalities of MR angiography and three-dimensional computed tomography (3D-CT)
      angiography. Initially, BPAS-MR imaging clearly demonstrated bilateral fusiform
      dilatations of the arterial wall, whereas MR angiography and 3D-CT angiography
      showed irregular, dilated, or interrupted inner contour of the arteries. Finally,
      BPAS-MR imaging demonstrated resolution of both aneurysms, and MR angiography
      demonstrated obstruction of the left VA and normal contours of the right VA.
      Combination of diagnostic tools such as BPAS-MR imaging and MR angiography is
      useful for evaluating the exact nature of dissected arteries and determining the
      temporal course.

PMID- 21869580
TI  - Anomalous origin of the ophthalmic artery from the anterior cerebral artery.
AB  - A 39-year-old woman presented with left visual disturbance and diplopia. Magnetic
      resonance imaging revealed a well-enhanced tumor in the left tentorium, cavernous
      sinus, and suprasellar region. Angiography demonstrated an abnormal origin of the
      ophthalmic artery from the anterior cerebral artery. The tumor was partially
      removed by left frontotemporal craniotomy with orbitozygomatic osteotomy.
      Intraoperatively, the anomalous origin of the ophthalmic artery was confirmed.
      This anatomical variation is extremely rare.

PMID- 21869581
TI  - Posterior reversible encephalopathy syndrome complicating intracranial hemorrhage
      after phenylpropanolamine exposure.
AB  - A 57-year-old woman suffered sudden onset of thunderclap headache after exposure
      to phenylpropanolamine (PPA), and subsequently developed posterior reversible
      encephalopathy syndrome (PRES) complicated by occipital intracranial hemorrhage
      (ICH) with cerebral vasoconstriction. PPA is well known to be associated with ICH
      and vasoconstriction, but this case illustrates the association with PRES. The
      danger of exposure to PPA and subsequent adverse events is quite low at present,
      but we must consider the possibility of exposure to medical agents in patients
      with repeated severe headache who have no organic disorder.

PMID- 21869582
TI  - Risk of rebleeding in arteriovenous malformations due to impaired venous drainage
      after radiosurgery.
AB  - A 27-year-old woman presented with rebleeding from an intracranial arteriovenous
      malformation (AVM) 6 years after radiosurgery. Cerebral angiography demonstrated
      venous drainage change into a single drainer and cortical reflux due to drainage
      occlusion into the superior sagittal sinus. During surgery, multiple small
      feeders thought to be occluded on preoperative angiography caused brain swelling,
      hindering resection of the AVM border plane. Flow changes after radiosurgery,
      especially impaired venous drainage, may have increased the tendency to
      rebleeding of the AVM. Scheduled angiography after radiosurgery is recommended,
      and retreatment for residual AVMs is preferable, especially if venous drainage
      change occurs.

PMID- 21869583
TI  - Treatment of a cervical carotid pseudoaneurysm that occurred years after
      laryngectomy and irradiation of a neck tumor.
AB  - A 62-year-old man presented with rupture of a pseudoaneurysm of the left common
      carotid artery (CCA) that was induced after radiation therapy and neck surgery.
      The initial treatment was an endovascular procedure to obliterate the aneurysm
      with coils, and a covered stent was placed in the parent artery. However, the
      patient presented with subsequent coil migration, wound infection, and left CCA
      stenosis. Direct surgical procedures were then performed, including resection of
      the pseudoaneurysm with coils and stent; replacement of the carotid artery with a
      saphenous vein graft; and operative wound reinforcement with a pedicle flap.
      Endovascular treatments may be chosen for vascular diseases after irradiation,
      because of the low risk of wound infection and fragility of the vessels, but the
      long-term outcomes of intravascular treatments are still unclear. In direct
      surgery, dissection of the adhesive tissue and adequate wound healing are
      difficult. Musculocutaneous flaps with vascular pedicles can achieve good
      results.

PMID- 21869584
TI  - Transarterial embolization with use of lipiodol and gelatin sponge for active
      nasal bleeding from hepatocellular carcinoma metastasis in the pituitary gland.
AB  - A 58-year-old man presented with a very rare case of pituitary metastasis from
      hepatocellular carcinoma with active nasal bleeding which was treated by
      transarterial embolization using ethiodized oil (Lipiodol) and gelatin sponge.
      After treatment, nasal bleeding ceased and tumor size decreased. The prognosis
      for patients with pituitary metastases is very poor, so aggressive treatment is
      recommended to alleviate symptoms. This minimally invasive approach may be a
      reasonable therapeutic option for pituitary metastases.

PMID- 21869585
TI  - Central nervous system primitive neuroectodermal tumor of spinal cord developing
      20 years after curative treatment of pineal tumor.
AB  - A 65-year-old male who had previously received curative treatment for a pineal
      tumor presented with an extremely rare case of primary central nervous system
      (CNS) primitive neuroectodermal tumor (PNET) of the spinal cord manifesting as
      progressive tetraparesis. Although the histology was not verified, highly
      radiosensitive tumor was suspected because of the benign clinical course for over
      20 years after only radiation therapy. Magnetic resonance imaging demonstrated an
      intramedullary tumor extending from C5 to T1. He underwent partial resection and
      histological examination revealed blue tumor with undifferentiated small round
      cells. Immunohistochemically, c-kit was negative but CD99 was strongly and
      diffusely positive. Therefore, rearrangement of the Ewing sarcoma gene was
      examined to determine the presence of peripheral type of PNET. The results were
      negative and systemic workup revealed no other disease. These findings led to the
      diagnosis of primary intramedullary CNS PNET of the spinal cord, and suggested
      that the spinal cord tumor occurred independently of the prior pineal disease.
      The residual tumor was controlled by postoperative local radiation therapy.

PMID- 21869586
TI  - Frontal sinus mucocele with intracranial extension associated with osteoma in the
      anterior cranial fossa.
AB  - A 70-year-old man presented with a rare case of paranasal osteoma with secondary
      mucocele extending intracranially, manifesting as a generalized convulsion.
      Computed tomography showed a large calcified tumor adjacent to the cystic mass in
      the left frontal lobe. He underwent left frontal craniotomy, and the cystic
      lesion was totally removed. Histological examination confirmed the diagnosis of
      osteoma and mucocele. The giant paranasal sinus osteoma prevented growth of the
      mucocele into orbital recess and extension into the orbital space and paranasal
      sinus. The mucocele disrupted the dura in the anterior cranial fossa, resulting
      in a giant cystic intracranial lesion. Frontal osteoplastic craniotomy was
      effective for exposing both lesions and plastic repair of the dural perforation
      to prevent cerebrospinal fluid leakage and secondary infection.

PMID- 21869587
TI  - Familial lateral temporal lobe epilepsy confirmed with intracranial
      electroencephalography and successfully treated by surgery.
AB  - Documentation of familial epilepsy is of paramount importance for identification
      of epilepsy-associated genes, elucidation of pathomechanisms of epilepsy, and
      development of treatment of epilepsy. We report a Japanese family with 5 members
      with lateral temporal lobe epilepsy beginning around the second decade of life.
      All seizures were intractable to medical treatment, and four patients underwent
      surgical treatment following long-term monitoring by intracranial
      electroencephalography with subdural electrodes, which revealed neocortical
      origins for the seizure. These four patients were successfully treated with
      surgery. The clinical features of this familial temporal lobe epilepsy seem to be
      different from those of previously reported types of familial temporal lobe
      epilepsy.

PMID- 21869588
TI  - Newly developed electromagnetic tracked flexible neuroendoscope.
AB  - Flexible endoscopes can be used in areas that are difficult to approach using
      rigid endoscopes. No current real-time navigation systems identify the tip of the
      flexible neuroendoscope. We have developed a flexible neuroendoscope mounted with
      a magnetic field sensor tip position-tracking system and evaluated the accuracy
      of this magnetic field neuronavigation system. Based on an existing flexible
      neuroendoscope, we created a prototype with a built-in magnetic field sensor in
      the tip. A magnetic field measurement device provides a magnetic field with a
      working volume of 500 * 500 * 500 mm in front of the device. The device consists
      of a flat field generator that creates a pulsed magnetic field, connected to a
      system control unit that interfaces with a computer. The magnetic field sensor
      (1.8 * 9 mm) was sealed in a site 0.9 mm from the endoscope tip. Accuracy of
      neuroendoscope tracking was measured using a three-dimensional coordinate
      measuring machine that measures the position of objects along 3 axes, with an
      error of about 3 um. The accuracy for this neuroendoscope with built-in magnetic
      field sensor was root mean square error of 1.2 mm and standard deviation of 0.5
      mm. This magnetic field neuronavigation system enables real-time tracking of the
      tip of the flexible neuroendoscope. Application of this flexible neuroendoscope
      to intraoperative navigation appears promising, and may provide new advantages
      for minimally invasive endoscopic surgery.

PMID- 21869589
TI  - A sodium channel blocker, pilsicainide, produces atrial post-repolarization
      refractoriness through the reduction of sodium channel availability.
AB  - Atrial fibrillation (AF) is the most common tachyarrhythmia. Shortening of atrial
      action potential duration (APD) and effective refractory period (ERP) is one of
      the crucial factors in the occurrence and maintenance of AF. ERP is usually
      shorter than APD, but ERP can be prolonged beyond action potential repolarization
      in some situations. It is termed as post-repolarization refractoriness (PRR) that
      is thought to be one of main anti-arrhythmic mechanisms of class I sodium channel
      blockers (SCBs). Most of anti-arrhythmic agents, including SCBs, have multi
      channel blocking effects. It is unknown whether atrial PRR with SCBs is
      associated with the reduction of sodium channel availability. We therefore
      explored the relationship between the reduction of sodium channel availability
      with a pure SCB (pilsicainide or tetrodotoxin) and atrial PRR using the left
      atrial appendage from male guinea pigs (each group, n = 3~10). Employing a
      standard microelectrode technique, we evaluated APD measured at 90%
      repolarization (APD(90)) and the sodium channel availability, judged from the
      maximal rate of rise of action potential (Vmax). At a 500-msec basic cycle length
      (BCL), pilsicainide prolonged atrial ERP assessed by a single extra-stimulus in
      response to the decrement of the Vmax in a dose-dependent manner without
      affecting APD(90). Furthermore, pilsicainide increased the ERP and decreased the
      Vmax in a rate-dependent manner without APD(90) prolongation at a shorter BCL
      (200 msec). Importantly, tetrodotoxin reproduced the effects of pilsicainide on
      atrial ERP, APD(90), and Vmax. These results indicate that SCBs produce atrial
      PRR through the reduction of sodium channel availability.

PMID- 21869590
TI  - Motivation of primary care physicians for participating in early intervention for
      psychosis in Japan.
AB  - People with psychosis as represented by schizophrenia experience lengthy delays
      between the onset and the start of treatment. This duration is called Duration of
      Untreated Psychosis (DUP). Since it has been indicated that shorter DUP leads to
      their better prognosis, early intervention has been a hot topic for decades in
      clinical psychiatry. In Japan, as any patient can visit either specialists or
      primary care physicians using medical insurance, a considerable portion of
      psychosis patients are supposed to visit the latter first. Thus, a role of
      primary care physicians seems keys of success in implementation of early
      intervention system in the Japanese society. In this study, to clarify the
      motivation of physicians to participate in early intervention, we sent postal
      questionnaires to 4030 private clinics throughout Japan, inquiring physicians'
      situations around psychiatric disorders. Seven hundred and fourteen
      questionnaires were used for analysis (17.7%). Among these 714 respondents, 364
      (51.0%) reported that they have willingness to participate in early intervention.
      Similarly, 494 (69.2%) were interested in psychiatric disorders, whereas only 168
      (23.5%) were confident in identifying schizophrenia. The interest in psychiatric
      disorders was most strongly associated with their willingness to participate
      (Odds ratio = 3.54 by logistic regression analysis). These results, therefore,
      suggest that the interest in psychiatric disorders motivates them to participate
      in early intervention for psychosis; this has considerable implications for
      future approach to build up early intervention system in Japan.

PMID- 21869591
TI  - Semaphorin 3A attenuates electrical remodeling at infarct border zones in rats
      after myocardial infarction.
AB  - Electrical remodeling at infarct border zone has been shown to contribute to the
      occurrence of ventricular arrhythmias after myocardial infarction (MI).
      Electrical remodeling is causally associated with sympathetic neural remodeling
      in MI. Semaphorin 3A (Sema3A), a potent neural chemorepellent for sympathetic
      axons, has been demonstrated to suppress sympathetic neural remodeling after MI.
      In the present study, we investigated whether treatment with Sema3A can
      ameliorate electrical remodeling at infarct border zones using a rat model of MI.
      Wistar rats underwent sham operation (n = 20), the ligation of left coronary
      artery (MI group, n = 30), MI with control adenovirus (Ad group, n = 30), and MI
      with Sema3A adenovirus (Sema3A group, n = 30). Eight weeks after treatment,
      electrophysiological properties including heart rate variability (HRV),
      monophasic action potential duration (MAPD) and effective refractory period (ERP)
      and the expression of arrhythmia-related ion channel proteins including Kv4.2,
      KChIP2 and Kir2.1 at the infarcted border of the left ventricle were examined.
      These channel proteins may be required for maintaining normal heart rhythm.
      Compared with the Ad group, Sema3A significantly increased HRV and shortened MAPD
      and ERP (all p < 0.05). The expression levels of Kv4.2, KChIP2 and Kir2.1
      proteins were significantly decreased in MI group and Ad group, compared to sham
      control. In contrast, the expression levels of these proteins were restored in
      Sema3A group, which may represent the molecular basis of the Sema3A-mediated
      inhibition of electrical remodeling. In conclusion, Sema3A can ameliorate
      electrical remodeling at infarct border zones after MI.

PMID- 21869592
TI  - Human neonatal neutrophils are resistant to apoptosis with lower caspase-3
      activity.
AB  - The incidence of neonatal inflammatory diseases remains high despite improved
      strategies for dealing with infection. Neutrophils are believed to play a
      significant role in neonatal inflammatory diseases due to their secretion of
      harmful mediators. Neutrophils rapidly undergo apoptosis following activation;
      dysregulation of the neutrophil apoptotic pathway may be an underlying mechanism
      of neonatal inflammatory disorders. In this study, we determined whether neonatal
      neutrophils are intrinsically resistant to apoptosis relative to their adult
      counterparts. Twelve healthy full-term newborn infants and 12 healthy adult
      volunteers, aged 20 to 45 years, were enrolled in this study. Neutrophils were
      isolated from umbilical cord blood or fresh venous peripheral blood, and
      neutrophils of each subject were cultured for up to 48 hours. Flow cytometric
      analysis revealed that spontaneous apoptosis of adult neutrophils increased with
      culture time (23% +/- 2% at 12 h, 49% +/- 4% at 24 h and 76% +/- 3% at 48 h),
      whereas the frequency of apoptosis was significantly lower in neutrophils from
      neonates (9% +/- 2% at 12 h, 30% +/- 4% at 24 h and 49% +/- 3% at 48 h) (p < 0.01
      for each time point). Importantly, the expression levels of caspase-3 mRNA and a
      precursor form of caspase-3 protein were lower in neonatal neutrophils than adult
      neutrophils, as judged by RT-PCR and Western blot analyses. Moreover, caspase-3
      activity was lower in neonatal neutrophils, compared to adult neutrophils. These
      findings suggest that neonatal neutrophils are intrinsically apoptosis-resistant,
      which may be due to the low expression of caspase-3.

PMID- 21869593
TI  - Lentivirus-mediated RNA interference targeting E2F-1 inhibits human gastric
      cancer MGC-803 cell growth in vivo.
AB  - The E2F-1 transcription factor is post-translationally modified and stabilized in
      response to various forms of DNA damage to regulate the expression of cell-cycle
      and pro-apoptotic genes. The sustained overexpression of E2F-1 is a
      characteristic feature of gastric cancer. In this study, we investigated the role
      of short hairpin RNA (shRNA) targeting E2F-1 gene on human gastric cancer MGC-803
      cell growth in vivo, and preliminarily revealed the mechanism. Thus, we
      constructed recombinant pGCSIL-GFP-shRNA-E2F-1 lentiviral vector to knock down
      E2F-1 expression in human gastric cancer MGC-803 cells in vivo, and studied the
      effect of E2F-1 shRNA on growth of MGC-803 tumor and evaluated its treatment
      efficacy. Our data demonstrated that in a mouse model of established gastric
      cancer, intratumor injection of lentiviral shRNA targeting E2F-1 definitely
      decreased the endogenous E2F-1 mRNA and protein expression in MGC-803 tumor, and
      inhibited tumor growth and promoted tumor cells apoptosis. Moreover, we found
      that E2F-1 shRNA increased the expression of phosphatase and tensin homolog
      (PTEN), activated caspase-3 and caspase-9, and suppressed nuclear factor (NF)
      kappaB expression in tumor tissue as determined by reverse transcription (RT)-PCR
      and western blotting. In summary, shRNA targeting of E2F-1 can effectively
      inhibits human gastric cancer MGC-803 cell growth in vivo and may be a potential
      therapeutic strategy for gastric cancer.

PMID- 21869594
TI  - Elg1, the major subunit of an alternative RFC complex, interacts with SUMO
      processing proteins.
AB  - PCNA is a homotrimeric ring with important roles in DNA replication and repair.
      PCNA is loaded and unloaded by the RFC complex, which is composed of five
      subunits (Rfc1-5). Three additional complexes that share with RFC the small
      subunits (Rfc2-5) and contain alternative large subunits were found in yeast and
      other eukaryotes. We have recently reported that one of these, the Elg1-RFC
      complex, interacts with SUMOylated PCNA and may play a role in its unloading
      during DNA repair. Here we report that a yeast-two-hybrid screen with the N
      terminus of Elg1(which interacts with SUMOylated PCNA) uncovered interactions
      with proteins that belong to the SUMO pathway, including Slx5 and Slx8, which
      form an E3 ubiquitin ligase that ubiquitinates SUMOylated proteins. Mutations in
      SLX5 result in a genomic instability phenotype similar to that of elg1 mutants.
      The physical interaction between the N terminus of Elg1 and Slx5 is mediated by
      poly-SUMO chains but not by PCNA modifications, and requires Siz2, but not Siz1,
      activity. Thus our results highlight the many important roles played by Elg1,
      some of which are PCNA-dependent and some PCNA-independent.

PMID- 21869595
TI  - Tumor suppression by Spinophilin.

PMID- 21869597
TI  - New insights into the biology of melanomas using a microRNA tool-KIT.

PMID- 21869596
TI  - MicroRNAs as molecular classifiers for cancer.

PMID- 21869598
TI  - Eating for two: how stromal fibroblasts might nurture adjacent carcinoma cells.

PMID- 21869599
TI  - Coordinated epigenetic regulation of autophagy and apoptosis.

PMID- 21869600
TI  - Reversing the Warburg effect through stromal autophagy.

PMID- 21869601
TI  - Unbearable stress: collapse of the SSeCKS/AKAP12 scaffold leads to senescence and
      transformation.

PMID- 21869602
TI  - Is there a "G spot" in sister chromatid cohesion resolution?

PMID- 21869604
TI  - Comparative analysis of essential collective dynamics and NMR-derived flexibility
      profiles in evolutionarily diverse prion proteins.
AB  - Collective motions on ns-MUs time scales are known to have a major impact on
      protein folding, stability, binding and enzymatic efficiency. It is also believed
      that these motions may have an important role in the early stages of prion
      protein misfolding and prion disease. In an effort to accurately characterize
      these motions and their potential influence on the misfolding and prion disease
      transmissibility we have conducted a combined analysis of molecular dynamic
      simulations and NMR-derived flexibility measurements over a diverse range of
      prion proteins. Using a recently developed numerical formalism, we have analyzed
      the essential collective dynamics (ECD) for prion proteins from 8 different
      species including human, cow, elk, cat, hamster, chicken, turtle and frog. We
      also compared the numerical results with flexibility profiles generated by the
      random coil index (RCI) from NMR chemical shifts. Prion protein backbone
      flexibility derived from experimental NMR data and from theoretical computations
      show strong agreement with each other, demonstrating that it is possible to
      predict the observed RCI profiles employing the numerical ECD formalism.
      Interestingly, flexibility differences in the loop between second beta strand
      (S2) and the second alpha helix (HB) appear to distinguish prion proteins from
      species that are susceptible to prion disease and those that are resistant. Our
      results show that the different levels of flexibility in the S2-HB loop in
      various species are predictable via the ECD method, indicating that ECD may be
      used to identify disease resistant variants of prion proteins, as well as the
      influence of prion proteins mutations on disease susceptibility or misfolding
      propensity.

PMID- 21869605
TI  - Can prion disease suspicion be supported earlier? Clinical, radiological and
      laboratory findings in a series of cases.
AB  - The subacute spongiform encephalopathies are prion diseases characterized by
      acute and rapid neurodegeneration that lead to the death of the patient within
      months to a few years. The epidemiology of CJD is complicated and the frequency
      in Mexico is unknown. We aim to describe the cases of prion disease in Mexico.
      Consecutive patients who met the diagnostic criteria by the WHO were enrolled. We
      describe 26 patients with clinical manifestations, imaging and laboratory studies
      compatible with prion disease. The mean age at onset was 52 years old. The main
      clinical manifestations were cognitive alterations (69%) followed by
      extrapyramidal movements (50%), abnormal cerebellar function (46%), behavioral
      alterations (46%), myoclonus (46%), and mood depression (23%), among other
      features. Half of the patients progressed rapidly to a state of akinetic mutism
      (53%). Only 2 (7.6%) patients had a family history of a similar disease. Time
      interval between onset and diagnosis varied between 71 days to 24 months, with a
      median of 6 months. The classical bilateral basal ganglia hyperintensities were
      present in the very early stage of the disease. Protein 14-3-3 immuneassay in the
      CSF was positive in all measured cases. Bilateral basal ganglia hyperintensities
      was the most important early finding, while protein 14-3-3 was a late finding and
      the results were usually obtained after the patient was discharged. Around 1.5
      cases of CJD cases per year are reported in our country. When suspected, MRI can
      support the diagnosis earlier than other studies.

PMID- 21869603
TI  - Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug
      resistance and response to radiation in breast cancer cells.
AB  - Elucidating the response of breast cancer cells to chemotherapeutic and hormonal
      based drugs and radiation is clearly important as these are common treatment
      approaches. Signaling cascades often involved in chemo-, hormonal- and radiation
      resistance are the Ras/PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK and p53 pathways. In
      the following studies we have examined the effects of activation of the
      Ras/PI3K/PTEN/Akt/mTOR cascade in the response of MCF-7 breast cancer cells to
      chemotherapeutic- and hormonal-based drugs and radiation. Activation of Akt by
      introduction of conditionally-activated Akt-1 gene could result in resistance to
      chemotherapeutic and hormonal based drugs as well as radiation. We have
      determined that chemotherapeutic drugs such as doxorubicin or the hormone based
      drug tamoxifen, both used to treat breast cancer, resulted in the activation of
      the Raf/MEK/ERK pathway which is often associated with a pro-proliferative, anti
      apoptotic response. In drug sensitive MCF-7 cells which have wild-type p53; ERK,
      p53 and downstream p21 (Cip-1 ) were induced upon exposure to doxorubicin. In
      contrast, in the drug resistant cells which expressed activated Akt-1, much lower
      levels of p53 and p21 (Cip1) were induced upon exposure to doxorubicin. These
      results indicate the involvement of the Ras/PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK
      and p53 pathways in the response to chemotherapeutic and hormonal based drugs.
      Understanding how breast cancers respond to chemo- and hormonal-based therapies
      and radiation may enhance the ability to treat breast cancer more effectively.

PMID- 21869606
TI  - Mucosal changes in a long-term bovine intestinal segment model following removal
      of ingesta and microflora.
AB  - The intestinal immune system influences responses to both enteric pathogens and
      commensal microflora but few models are available to analyze mucosal immune
      responses to either enteric pathogens or commensal microflora. We surgically
      isolated ileal segments in 2-3 week old calves, infused antibiotics, and
      subdivided each segment into three compartments. Following a 6-8 week period the
      isolated ileal segments appeared grossly normal in 4 of 5 calves, retained
      compartmentalization, and contents were culture positive for either Enterococcus
      spp. or Escherichia coli. In a second experiment, isolated ileal segments were
      examined following a 9-11 month period and appeared grossly normal with
      compartmentalization retained in 8 of 11 animals. Streptococcus spp or
      Escherichia coli were cultured from segment contents collected from 3 of these 8
      animals. Histology revealed a marked reduction in villus height in isolated ileal
      segments despite sustained crypt epithelium proliferation. Lymphoid follicles in
      ileal Peyer's patches were reduced in size but remained sites of active
      lymphoproliferation within segments. Significant mucosal T cell, macrophage, and
      dendritic cell depletion was observed in isolated ileal segments and T cell and
      NK cell depletion increased significantly in the absence of culturable bacteria.
      Finally, Toll-like receptor (TLR)-4 expression was decreased but TLR-5 and -6
      expression increased in ileal segments. Thus, isolated ileal segments remained
      relatively stable for prolonged periods and significant changes in mucosal
      leukocyte populations were correlated with the presence or absence of culturable
      microflora. Stable, as opposed to sterile, isolated ileal segments provide an
      opportunity to analyze bovine mucosal immune responses in the presence or absence
      of commensal microflora.

PMID- 21869607
TI  - Intestinal steroid profiles and microbiota composition in colitic mice.
AB  - Reduced gut microbiota diversity in conjunction with a bloom of few bacterial
      species is a common feature in inflammatory bowel disease (IBD) patients.
      However, the environmental changes caused by inflammation and their possible
      impact on the microbiota are largely unknown. Since IBD is associated with an
      impaired intestinal steroid metabolism, we hypothesized that changes in
      intestinal steroid and particularly bile acid (BA) concentrations affect
      microbial communities. We used Interleukin-10 deficient (IL-10-/-) mice as a
      model for chronic gut inflammation. Healthy wild-type mice served as controls. In
      these animals, intestinal steroid concentrations and gut microbial diversity were
      analyzed at 24 weeks of age. The IL 10-/- mice developed moderate inflammation in
      cecum and colon and colorectal tumor formation was observed in 55 % of the
      animals. Compared to the healthy conditions, gut inflammation was associated with
      higher intestinal cholesterol and cholic acid concentrations and a reduced
      microbial diversity. The latter was accompanied by a proliferation of
      Robinsoniella peoriensis, Clostridium innocuum, Escherichia coli, and
      Enterococcus gallinarum. All these species proved to be highly bile acid
      resistant. We concluded that chronic colitis in IL-10-/- mice is associated with
      changes in intestinal steroid profiles. These changes may be due to alterations
      in gut microbiota composition or vice versa. Whether the bacterial sterol and
      bile acid metabolism is implicated in colitis and colorectal carcinoma etiology
      remains to be clarified.

PMID- 21869608
TI  - Tertiary lymphoid tissues in the colon: friend and foe.
AB  - In mammals, a variety of different lymphoid tissues have evolved as an integral
      part of the immune system that allows the host to survive in a sometimes hostile
      environment. While the development of secondary lymphoid organs is programmed in
      the fetus, the induction of other lymphoid structures like isolated lymphoid
      follicles (ILFs) in the gut or tertiary lymphoid tissues (tLT) need additional
      external triggers after birth. It is well established that for the development of
      secondary lymphoid organs, as well as ILFs, RORgt expressing lymphoid tissue
      inducer (LTi) cells play an important role. Yet, the requirement of these cells
      for tLT induction, especially in the gut, was less clear. Here, I will discuss
      recent data demonstrating that RORgt expressing LTi cells are not required for
      the development of tLT in the colon. In contrast, such structures even develop
      spontaneously in the absence of RORgt. In RORgt (-/-) mice, this is part of the
      host's strategy to establish a viable homeostasis between the intestinal
      microbiota and the host, despite the loss of important components of the
      intestinal immune system in these mice. Although this highlights the amazing
      capacity of the immune system for adaptation, I will also discuss the adverse
      effects of such a compensatory immune mechanism for the host.

PMID- 21869609
TI  - Generation of cells that ignore the effects of PIP3 on cytoskeleton.

PMID- 21869610
TI  - Pathogenic DNA: cytosolic DNA promotes inflammation in psoriasis.

PMID- 21869611
TI  - Nuclear actin in transcriptional reprogramming by oocytes: are actin nucleators
      key players?

PMID- 21869612
TI  - Acetyl-CoA drives the transcriptional growth program in yeast.

PMID- 21869613
TI  - CEE-ing is believing: bioscience ventures in Central and Eastern Europe.
AB  - Bioscience ventures in Central and Eastern Europe are becoming a presence in
      world healthcare markets despite a perennially short supply of venture funding
      and other support mechanisms relative to other world economic regions. Here are
      three up-and-coming CEE stories worth keeping an eye on.

PMID- 21869614
TI  - Usefulness of indocyanine green angiography to depict the distant retinal
      vascular anomalies associated with branch retinal vein occlusion causing serous
      macular detachment.
AB  - PURPOSE: To report the usefulness of indocyanine green angiography (ICGA) to
      depict the retinal vascular anomalies associated with distant branch retinal vein
      occlusion resulting in serous retinal detachment at the macula. METHODS: This was
      a retrospective, case series of 6 patients (6 eyes) with serous retinal
      detachments. Fluorescein angiography and ICGA showed that those 6 eyes had a
      distant branch retinal vein occlusion. The characteristics in ophthalmic
      examinations such as fundus appearance, fluorescein angiography, ICGA, optical
      coherence tomography, and clinical courses were evaluated. RESULTS: In addition
      to serous retinal detachments, five eyes exhibited hard exudates around the
      macula. Fluorescein angiography and ICGA clearly showed the vessel occlusion;
      however, no apparent abnormalities appeared in the macular area in any of the
      eyes. In four eyes, early-phase ICGA depicted the retinal vascular anomalies
      within the area of venous occlusion and those were seen as hyperfluorescent
      patches on late-phase ICGA. In two eyes, punctate hyperfluorescent spots were
      seen in the area of venous occlusion on late-phase ICGA. Optical coherence
      tomography depicted a serous retinal detachment at the macula and retinal
      swelling in the outer nuclear layer from the macula to the hyperfluorescent
      abnormalities on ICGA. The macular serous retinal detachments were resolved
      within 3 months after laser photocoagulation was applied to the hyperfluorescent
      areas on ICGA. CONCLUSION: Leakage from subsequent vascular anomalies after
      branch retinal vein occlusion can cause submacular fluid. Indocyanine green
      angiography is useful for detecting the causative vascular regions of the fluid.

PMID- 21869615
TI  - Retrospective hemolysis comparison between patients with centrifugal
      biventricular assist and left ventricular assist devices.
AB  - Little is known about the hemolysis rate in the case of concomitant implantation
      of two continuous flow pumps for the treatment of biventricular heart failure. We
      present a retrospective study comparing the hemolysis parameters in patients
      supported with one implantable centrifugal pump of the type HeartWare HVAD used
      as a left ventricular assist device (LVAD) and with two pumps as a biventricular
      assist device (BiVAD). A total of 20 consecutive patients who received HeartWare
      BiVAD (n = 10) and LVAD (n = 10) support at our institution between September
      2009 and September 2010 were examined. Hemolysis- and anemia-related parameters
      were analyzed after 2 weeks, 5 weeks, 3 months, and 6 months of support.
      Preoperative levels of hemoglobin, lactate dehydrogenase (LDH), and total
      bilirubin were similar in both groups. There were no differences in LDH, plasma
      free hemoglobin (fHB), or total bilirubin levels postoperatively for up to 6
      months. Only the haptoglobin level was lower in BiVAD recipients up to 3 months
      after surgery: 2nd week (63.5 [range: 8-237] mg/dl vs. 151 [range: 11-263] mg/dl,
      p = 0.05), 5th week (67 [range: 8-196] mg/dl vs. 215 [range: 56-292] mg/dl, p =
      0.046), and after 3rd month (42 [range: 8-205] mg/dl vs. 220 [range: 157-256]
      mg/dl, p = 0.048). Our retrospective analysis of BiVAD HeartWare and LVAD
      HeartWare recipients showed a lack of a clinically important degree of hemolysis
      when two centrifugal HeartWare pumps are used for biventricular support.

PMID- 21869616
TI  - In vivo evaluation of a new surfactant polymer coating mimicking the glycocalyx
      of endothelial cells.
AB  - The purpose of this study was to demonstrate that a proprietary surfactant
      polymer (SP) coating does not adversely affect the hemodynamic performance of
      cardiopulmonary bypass (CPB) or gas exchange in oxygenators. The new coating was
      applied to a CPB circuit including cannulae, reservoir, oxygenator, and blood
      pump implanted into 12 pigs, divided into groups with either coated or noncoated
      pumps. CPB flow was maintained at a fixed level of approximately 2.4 L/min for 6
      hours with full heparinization. Hemodynamic data and pump performance were
      recorded every hour, and blood samples were taken every 2 hours. After sacrifice,
      the CPB circuit and major organs were macroscopically examined. There was no
      significant difference in the oxygen transfer rate between the two groups. The
      coating did not adversely affect oxygenator inlet or outlet pressures. There was
      no significant difference between the two groups in microthrombi seen in the
      oxygenators. No thromboemboli were noted in the major organs on gross or
      histologic examination. In conclusion, this new SP coating did not decrease gas
      exchange performance, and its biocompatibility evaluations revealed no
      differences between coated and noncoated groups under aggressive heparin use.

PMID- 21869617
TI  - A comparative study of helical-type and traditional-type artery bypass grafts:
      numerical simulation.
AB  - Preliminary studies on an individual helical graft indicated that its
      hemodynamics might be improved while pressure drop increased compared with a
      traditional graft. Aiming to investigate whether the benefits of a helical graft
      to hemodynamics dominate its deficits, this study numerically carried out
      comparative study of helical-type artery bypass graft (ABG) and traditional-type
      ABG under both steady and pulsatile flow conditions. The results showed that a
      helical-type ABG resulted in reduced oscillating shear index, improved wall shear
      stress, enhanced flow mixing and three-dimensionality, and improved flow behavior
      at the distal anastomosis and occluded section of the host vessel compared with
      traditional-type ABG. More important, although a helical-type ABG did increase
      the pressure drop compared with a traditional one, its maximum percentage
      increase during a cardiac cycle was <21% which is still within physiological
      sense. Therefore, we believe that the adoption of helical bypass could help to
      prevent intimal hyperplasia (IH) and thrombosis at the distal anastomosis and
      improve the graft patency while keeping clinical maintenance. This investigation
      provided an important basis for the clinical applications and theory support of
      helical graft.

PMID- 21869618
TI  - Safe transport of critically ill adult patients on extracorporeal membrane
      oxygenation support to a regional extracorporeal membrane oxygenation center.
AB  - Patients with severe cardiac or pulmonary failure who require transport to
      specialized hospitals currently pose a challenge. Mechanical support in the form
      of extracorporeal membrane oxygenation (ECMO) may increase the safety of
      transporting such patients to an institution where they will have access to
      advanced medical therapy. Over 2.5 years, 17 patients were successfully
      cannulated and placed on a simplified ECMO circuit at other institutions and
      transported via ambulance to our hospital. Fourteen patients with acute
      respiratory distress syndrome (ARDS) were placed on venovenous (VV) ECMO. Two
      patients with isolated cardiogenic shock and one patient with ARDS were placed on
      venoarterial (VA) ECMO. The two cardiogenic shock patients were converted to a
      biventricular assist device shortly after arrival. The median unit-to-unit
      transport time was 60 minutes (interquartile range 50-92 minutes), and the median
      distance traveled was 23 miles (interquartile range 17-55 miles). There was no
      transport-related morbidity or mortality. The median duration of ECMO support was
      8 days (interquartile range 4-11 days). Thirteen patients (76%) were successfully
      decannulated. Ten patients (59%) were weaned from the ventilator, and nine
      patients (53%) survived up to 3 months and were discharged from the hospital.
      Critically ill patients with severe ARDS or cardiogenic shock can be safely
      transported on VV or VA ECMO support to regional ECMO centers. As the indications
      and demands for ECMO support expand, so will the role for transporting patients
      on ECMO.

PMID- 21869619
TI  - Central venous stenosis among hemodialysis patients is often not associated with
      previous central venous catheters.
AB  - It is widely assumed that central venous stenosis (CVS) is most commonly
      associated with previous central venous catheterization among the chronic
      hemodialysis (HD) patients. We evaluated the validity of this assumption in this
      retrospective study. The clinical records from 2,856 consecutive HD patients with
      vascular access failure during a 5-year period were reviewed, and a total of 26
      patients with symptomatic CVS were identified. Combined with radiological
      findings, their clinical characteristics were examined. Only seven patients had a
      history of internal jugular dialysis catheterization. Diagnostic multidetector
      row computed tomography angiography showed that 7 of the 19 patients with no
      history of catheterization had left innominate vein stenosis due to extrinsic
      compression between the sternum and arch vessels. These patients had a shorter
      period from the time of creation of the vascular access to the initial referral
      (9.2 +/- 7.6 months) than the rest of the patients (35.5 +/- 18.6 months, p =
      0.0017). Our findings suggest that cases without a history of central venous
      catheterization may not be rare among the HD patients with symptomatic CVS.
      However, those still need to be confirm by larger prospective studies of overall
      chronic HD patients with symptomatic CVS.

PMID- 21869620
TI  - Blunted insulinemia using high dialysate glucose concentration during
      hemodialysis.
AB  - The benefit of high glucose concentrations in the dialysate remains under debate.
      The aim of this study was to analyze and to compare the acute insulin response
      using a common but high glucose concentration in the dialysate representing a
      parenteral mode of glucose administration to oral glucose administration in
      stable and fasting nondiabetic hemodialysis patients during their routine
      hemodialysis session. Glucose was either given by a standardized oral load (75 g)
      or using a glucose concentration of 11.1 mmol/L (200 mg/dL) in the dialysate for
      the duration of an hour. The insulin response per unit glucose stimulus was
      determined from the slope of paired insulin and glucose concentrations measured
      in 15-minute intervals using standard techniques. This slope is mathematically
      equivalent to the insulinogenic index (IG) and has been shown to be independent
      of extracorporeal clearance by ongoing hemodialysis. In 10 subjects, the IG was
      9.3 +/- 2.6 U/mol with oral glucose delivery but only one-third of that value
      (3.0 +/- 1.1 U/mol, p < 0.001) when glucose was delivered through the dialysate.
      Administration of glucose using dialysate thus leads to a blunted insulin
      response per unit glucose stimulus. This may cause prolonged hyperglycemia which
      should be avoided in patients treated with hemodialysis.

PMID- 21869621
TI  - Continuous renal replacement therapy with Prismaflex HF20 disposable set in
      children from 4 to 15 kg.
AB  - Continuous venovenous hemodiafiltration (CVVHDF) in infants is challenging due to
      a lack of specific and widely available technology. There is need for high
      precision of fluid balance and hemodynamic stability. The aim of this study is to
      report the first experience with the newly developed Prismaflex HF20 disposable
      set (HF20 set) in infants with CVVHDF. We provided safe treatment in four infants
      (4-14 kg) suffering from acute renal failure with the HF20 set. Treatment
      monitoring included patients' blood pressure, patients' weight change, and fluid
      balance. The anticoagulation was performed with unfractionated heparin. We used
      commercially available bicarbonate-buffered solutions as dialysate fluid and
      substitution fluid. At start and during the treatment, the patients showed
      hemodynamic stability. Desired fluid balance was achieved in all patients during
      the treatment periods of 49-102 hours. No complications occurred. This report
      presents CVVHDF experience on the feasibility and safety of the HF20 set in
      infants. It can be used in CVVHDF or hemodialysis mode. Treatments were well
      tolerated in all patients, and flow rate adaptability to infants' needs was very
      acceptable, and the usage of this device was easy and safe.

PMID- 21869622
TI  - How to teach artificial organs.
AB  - Artificial organs education is often an overlooked field for many bioengineering
      and biomedical engineering students. The purpose of this article is to describe
      three different approaches to teaching artificial organs. This article can serve
      as a reference for those who wish to offer a similar course at their own
      institutions or incorporate these ideas into existing courses. Artificial organ
      classes typically fulfill several ABET (Accreditation Board for Engineering and
      Technology) criteria, including those specific to bioengineering and biomedical
      engineering programs.

PMID- 21869623
TI  - Pitch matching psychometrics in electric acoustic stimulation.
AB  - OBJECTIVE: Combined electric-acoustic stimulation (EAS) is a therapeutic option
      for patients with severe to profound mid- and high-frequency hearing loss while
      low-frequency hearing is mostly unaffected. The present study investigates
      bimodal pitch matching in EAS users as a function of the angular placement of
      electrodes. Results are compared with data obtained from previous pitch matching
      studies. Knowledge of electric and acoustic pitch mapping may be important for
      effective fitting to control the frequency range of acoustic and electric
      processing. DESIGN: Pitch adjustment experiments were conducted in eight subjects
      with residual hearing in the opposite ear as well as in the implanted ear. Four
      subjects received a standard 31.5-mm electrode array and four subjects received
      the shorter, more flexible 24-mm FLEX electrode array (PULSARCI100 or SONATATI100
      stimulator, MED-EL, Innsbruck, Austria). The subjects' task was to listen to
      single-electrode stimuli presented at a fixed rate (800 pulses per second) via
      the cochlear implant and to adjust the frequency of the acoustic stimulus until
      the perceived pitch matched the perception of the electrically conveyed stimulus.
      Two to four of the most apical electrodes were tested depending on the range of
      the individual's residual hearing. Postoperative x rays (modified Stenver's view)
      were analyzed to compare individual pitch matching data in terms of the electrode
      arrays' insertion angle. RESULTS: The average mean frequency match for the most
      apical electrode 1 in EAS subjects implanted with the FLEX array was 583 Hz,
      while for the two subjects with a deep insertion of the 31.5-mm standard
      electrode array, the matches were 128 and 223 Hz. Because the residual hearing in
      the EAS subgroup was rather limited in the high-frequency range, a limited number
      of basal electrodes were assessed to determine the slope of the electric
      place/pitch function. A considerable variation in terms of the individual pitch
      function was observed. The slope of the pitch function varied to a large extent
      among subjects. The differences between contra- and ipsilateral adjustments were
      very small (mean average 14 Hz) and within the range of the variance (average SD
      124 Hz). CONCLUSIONS: The application of a pitch matching procedure to assess the
      electric/acoustic crossover frequency is feasible. In the present study, ipsi-
      and contralateral pitch matches made by EAS patients were nearly equal;
      therefore, a severe alteration in the excitation pattern of the basilar membrane
      in the implanted ear can be ruled out.

PMID- 21869624
TI  - The effect of 40-m repeated sprint training on maximum sprinting speed, repeated
      sprint speed endurance, vertical jump, and aerobic capacity in young elite male
      soccer players.
AB  - The purpose of this study was to examine the effect of 10 weeks' 40-m repeated
      sprint training program that does not involve strength training on sprinting
      speed and repeated sprint speed on young elite soccer players. Twenty young well
      trained elite male soccer players of age (+/-SD) 16.4 (+/-0.9) years, body mass
      67.2 (+/-9.1) kg, and stature 176.3 (+/-7.4) cm volunteered to participate in
      this study. All participants were tested on 40-m running speed, 10 * 40-m
      repeated sprint speed, 20-m acceleration speed, 20-m top speed, countermovement
      jump (CMJ), and aerobic endurance (beep test). Participants were divided into
      training group (TG) (n = 10) and control group (CG) (n = 10). The study was
      conducted in the precompetition phase of the training program for the
      participants and ended 13 weeks before the start of the season; the duration of
      the precompetition period was 26 weeks. The TG followed a Periodized repeated
      sprint training program once a week. The training program consisted of running 40
      m with different intensities and duration from week to week. Within-group results
      indicate that TG had a statistically marked improvement in their performance from
      pre to posttest in 40-m maximum sprint (-0.06 seconds), 10 * 40-m repeated sprint
      speed (-0.12 seconds), 20- to 40-m top speed (-0.05 seconds), and CMJ (2.7 cm).
      The CG showed only a statistically notable improvement from pre to posttest in 10
      * 40-m repeated sprint speed (-0.06 seconds). Between-group differences showed a
      statistically marked improvement for the TG over the CG in 10 * 40-m repeated
      sprint speed (-0.07 seconds) and 20- to 40-m top speed (-0.05 seconds), but the
      effect of the improvement was moderate. The results further indicate that a
      weekly training with repeated sprint gave a moderate but not statistically marked
      improvement in 40-m sprinting, CMJ, and beep test. The results of this study
      indicate that the repeated sprint program had a positive effect on several of the
      parameters tested. However, because the sample size in this study is 20
      participants, the results are valid only for those who took part in this study.
      Therefore, we advice to use repeated sprint training similar to the one in this
      study only in periods where the players have no speed training included in their
      program. Furthermore, the participants in this study should probably trained
      strength, however, benefits were observed even without strength training is most
      likely to be caused by the training specificity.

PMID- 21869625
TI  - Small-sided games in soccer: amateur vs. professional players' physiological
      responses, physical, and technical activities.
AB  - The aim of this study was to examine the relationship between the playing level
      in soccer (i.e., amateur vs. professional players) and the physiological impact,
      perceptual responses, time-motion characteristics, and technical activities
      during various small-sided games (SSGs). Twenty international players (27.4 +/-
      1.5 years and 17.4 +/- 0.8 km.h(-1) of vVO(2)max) and 20 amateur players of the
      fourth French division (26.3 +/- 2.2 years and 17.0 +/- 1.2 km.h(-1) of
      vVO(2)max) played 9 SSGs (i.e., 2 vs. 2, 3 vs. 3, and 4 vs. 4) in which the
      number of ball touches authorized by possession varied (1 ball touch authorized =
      1T, 2 ball touches authorized = 2T, and Free Play = FP). Heart rate (HR), blood
      lactate ([La]), subjective perception of effort (rating of perceived exertion
      [RPE]), physical performance, and technical performance of all players were
      analyzed during all SSGs. Across the various SSGs, amateurs completed a lower
      percent of successful passes (p < 0.01), recorded higher RPE and [La] values,
      lost a greater amount of ball possessions (p < 0.001), and covered less total
      distance with respect to sprinting and high-intensity running (HIR). The HR
      responses, however, were similar when expressed as %HRmax and %HRreserve. The
      comparison of the professional and amateur soccer players' activities during SSGs
      showed that the playing level influenced the physiological responses, physical
      and technical activities. Consequently, this study has shown that the main
      differences between elite and amateur players within SSGs concerned their
      capacity to perform high-intensity actions (HIR and sprints) and execute various
      technical abilities (in particular number of ball lost per possession and
      percentage of successful passes).

PMID- 21869626
TI  - Antioxidant status and oxidative stress at rest and in response to acute exercise
      in judokas and sedentary men.
AB  - It is well recognized that acute strenuous exercise is accompanied by an increase
      in free-radical production and subsequent oxidative stress, in addition to
      changes in blood antioxidant status. Chronic exercise provides protection against
      exercise-induced oxidative stress by upregulating endogenous antioxidant defense
      systems. Little is known regarding the protective effect afforded by judo
      exercise. Therefore, we determined antioxidant and oxidative stress biomarkers at
      rest and in response to acute exercise in 10 competitive judokas and 10 sedentary
      subjects after mixed exercise (anaerobic followed by aerobic). The subjects
      performed a Wingate test, followed by 30 minutes of aerobic exercise performed at
      60% of maximal aerobic power. Blood samples were taken, by an intravenous
      catheter, at rest (R), immediately after the physical exercise (P0), and at 5
      (P5), 10 (P10), and 20 (P20) minutes postexercise. The measured parameters
      included the activity of the antioxidant enzymes superoxide dismutase,
      glutathione peroxidase, and glutathione reductase, in addition to alpha
      tocopherol, and total antioxidant status. Malondialdehyde was measured as a
      representation of lipid peroxidation. At rest, the judokas had higher values for
      all antioxidant and oxidative stress markers as compared to the sedentary
      subjects (p < 0.05). Plasma concentrations of all parameters except for alpha
      tocopherol increased significantly above resting values for both the judokas and
      sedentary subjects (p < 0.05) and remained elevated at 20 minutes postexercise. A
      significant postexercise decrease was observed for alpha-tocopherol (p < 0.05) at
      P20 for judokas and at P5 for sedentary subjects. These data indicate that
      competitive judo athletes have higher endogenous antioxidant protection compared
      to sedentary subjects. However, both groups of subjects experience an increase in
      exercise-induced oxidative stress that is not different.

PMID- 21869627
TI  - Match analysis of elite adolescent team handball players.
AB  - The purposes of this study were to examine the activity profile of elite
      adolescent players during regular team handball games and to compare the physical
      and motor performance of players between the first and second halves of a match.
      Activity patterns (video analysis) and heart-rate (HR) responses (telemetry) were
      monitored in top national-division adolescent players (18 men, aged 15.1 +/- 0.6
      years) throughout 6 regulation games (25-minute halves with a 10-minute
      interval). The total distance covered averaged 1,777 +/- 264 m per game (7.4%
      less in the second than in the first half, p > 0.05). Players ran 170 +/- 24 m at
      high intensity and 86 +/- 12 m at maximal speed, with 32 +/- 6 bouts of running
      (duration 2.3 +/- 0.3 seconds) at speeds > 18 km.h(-1); they stood still for 16%
      of the playing time. The mean HR during play was 172 +/- 2 b.min(-1) (82 +/- 3%
      of maximal HR). Blood lactate concentrations at the end of the first and second
      halves were 9.7 +/- 1.1 and 8.3 +/- 0.9 mmol.L(-1), respectively (difference p <
      0.05). We conclude that adolescent handball players cover less distance and
      engage in fewer technical actions in the second half of a match. This indicates
      that team handball is physiologically very demanding. The practical implication
      is that coaches should seek to sustain performance in the second period of a game
      by modifying playing tactics and maximizing both aerobic and anaerobic fitness
      during training sessions.

PMID- 21869628
TI  - Effects of 8-week in-season upper and lower limb heavy resistance training on the
      peak power, throwing velocity, and sprint performance of elite male handball
      players.
AB  - The aims of this study were to test the potential of in-season heavy upper and
      lower limb strength training to enhance peak power output (Wpeak), vertical jump,
      and handball related field performance in elite male handball players who were
      apparently already well trained, and to assess any adverse effects on sprint
      velocity. Twenty-four competitors were divided randomly between a heavy
      resistance (HR) group (age 20 +/- 0.7 years) and a control group (C; age 20 +/-
      0.1 years). Resistance training sessions were performed twice a week for 8 weeks.
      Performance was assessed before and after conditioning. Peak power (W(peak)) was
      determined by cycle ergometer; vertical squat jump (SJ) and countermovement jump
      (CMJ); video analyses assessed velocities during the first step (V(1S)), the
      first 5 m (V(5m)), and between 25 and 30 m (V(peak)) of a 30-m sprint. Upper limb
      bench press and pull-over exercises and lower limb back half squats were
      performed to 1-repetition maximum (1RM). Upper limb, leg, and thigh muscle
      volumes and mean thigh cross-sectional area (CSA) were assessed by anthropometry.
      W(peak) (W) for both limbs (p < 0.001), vertical jump height (p < 0.01 for both
      SJ and CMJ), 1RM (p < 0.001 for both upper and lower limbs) and sprint velocities
      (p < 0.01 for V(1S) and V(5m); p < 0.001 for V(peak)) improved in the HR group.
      Upper body, leg, and thigh muscle volumes and thigh CSA also increased
      significantly after strength training. We conclude that in-season biweekly heavy
      back half-squat, pull-over, and bench-press exercises can be commended to elite
      male handball players as improving many measures of handball-related performance
      without adverse effects upon speed of movement.

PMID- 21869629
TI  - Intensity of official Futsal matches.
AB  - The purpose of this study was to assess the intensity of official Futsal matches,
      expressed in different ways. Fourteen male professional Futsal players from a
      First Division Brazilian team volunteered to participate in this study. Maximal
      oxygen uptake (VO(2)max) and the heart hate (HR) and oxygen uptake (VO(2))
      correlation were determined for each player. The match intensity was estimated
      from the players' average HR measured during 13 National Futsal League matches.
      The HR measurements were obtained while the players were in the court but the
      values recorded while the players were sitting on the bench were not considered.
      In addition, these HR values were used to estimate the intensity of the effort
      expressed as a percentage of the maximal HR (% HRmax), percentage of VO(2)max (%
      VO(2)max), kilocalories per minute (kcal.min(-1)), and total caloric expenditure.
      The mean intensity of the matches was 86.4 +/- 3.8% HRmax, 79.2 +/- 9.0%
      VO(2)max, 18.0 +/- 2.2 kcal.min(-1), and 313 +/- 9.3 kcal. It was concluded that
      official Futsal matches have high intensity when expressed in the different ways
      used in this study. The information provided by this research can be used for
      planning the athletes' workouts, diets, and resting periods.

PMID- 21869630
TI  - Relationship between changes in total-body water and fluid distribution with
      maximal forearm strength in elite judo athletes.
AB  - Among judo athletes, strong grip strength is crucial for performing offensive and
      defensive maneuvers that rely predominantly on forearm maximal strength (FMS).
      The study aims were to evaluate changes in total-body water (TBW) and its
      compartments (extracellular water [ECW] and intracellular water [ICW]) and their
      relationship with loss of FMS in elite judo athletes. At baseline (weight
      stability), 27 male elite athletes were evaluated (age: 23.2 +/- 2.8 years) and
      again evaluated 1-3 days before competition. Athletes were free to gain or lose
      weight based upon their specific competition needs. Using dilution techniques
      (deuterium and bromide), TBW and ECW were estimated, and ICW was calculated (ICW
      = TBW - ECW). Fat, fat-free mass, and appendicular lean soft tissue (LST) were
      assessed by dual-energy x-ray absorptiometry. Handgrip was used to assess FMS.
      Using a reduction of 2% as a representative outcome for decreased FMS, 10
      athletes were identified as having lost FMS, whereas 17 changed <2% or gained.
      Comparison of means and logistic regression analysis were performed. Results from
      baseline to before competition indicated that those who lost >=2% of FMS
      significantly decreased TBW and ICW by -2.7 +/- 3.0 and -4.4 +/- 4.2%,
      respectively. The groups differed in ICW changes (-4.4 +/- 4.2 vs. 1.9 +/- 6.1%),
      respectively, for those who lost FMS by >=2%. The ICW changes, but not in TBW or
      ECW, significantly predicted the risk of losing FMS (beta = 0.206; p = 0.027),
      even adjusting for weight and arm LST changes. These findings indicated that
      reductions in ICW increased the risk of losing grip strength in elite judo
      athletes.

PMID- 21869631
TI  - Changes in biomechanical properties during drop jumps of incremental height.
AB  - The purpose of this study was to investigate changing biomechanical properties
      with increasing drop jump height. Sixteen physically active college students
      participated in this study and performed drop jumps from heights of 20, 30, 40,
      50, and 60 cm (DJ20-DJ60). Kinematic and kinetic data were collected using 11
      Eagle cameras and 2 force platforms. Data pertaining to the dominant leg for each
      of 3 trials for each drop height were recorded and analyzed. Statistical
      comparisons of vertical ground reaction force (vGRF), impulse, moment, power,
      work, and stiffness were made between different drop jump heights. The peak vGRF
      of the dominant leg exceeded 3 times the body weight during DJ50 and DJ60; these
      values were significantly greater than those for DJ20, DJ30, and DJ40 (all p <
      0.004). The height jumped during DJ60 was significantly less than that during
      DJ20 and DJ30 (both p = 0.010). Both the landing impulse and total impulse during
      the contact phase were significantly different between each drop height (all p <
      0.036) and significantly increased with drop height. There were no significant
      differences in the takeoff impulse. Peak and mean power absorption and negative
      work at the knee and ankle joints during DJ40, DJ50, and DJ60 were significantly
      greater than those during DJ20 and DJ30 (all p < 0.049). Leg, knee, and ankle
      stiffness during DJ60 were significantly less than during DJ20, DJ30, and DJ40
      (all p < 0.037). The results demonstrated that drop jumps from heights >40 cm
      offered no advantages in terms of mechanical efficiency (SSC power output) and
      stiffness. Drop jumps from heights in excess of 60 cm are not recommended because
      of the lack of biomechanical efficiency and the potentially increased risk of
      injury.

PMID- 21869632
TI  - Isokinetic knee joint evaluation in track and field events.
AB  - The purpose of this study was to evaluate maximal torque of the knee flexors and
      extensors, flexor/extensor ratios, and maximal torque differences between the 2
      lower extremities in young track and field athletes. Forty male track and field
      athletes 13-17 years old and 20 male nonathletes of the same age participated in
      the study. Athletes were divided into 4 groups according to their age and event
      (12 runners and 10 jumpers 13-15 years old, 12 runners and 6 jumpers 16-17 years
      old) and nonathletes into 2 groups of the same age. Maximal torque evaluation of
      knee flexors and extensors was performed on an isokinetic dynamometer at 60
      degrees .s(-1). At the age of 16-17 years, jumpers exhibited higher strength
      values at extension than did runners and nonathletes, whereas at the age of 13-15
      years, no significant differences were found between events. Younger athletes
      were weaker than older athletes at flexion. Runners and jumpers were stronger
      than nonathletes in all relative peak torque parameters. Nonathletes exhibited a
      higher flexor/extensor ratio compared with runners and jumpers. Strength
      imbalance in athletes was found between the 2 lower extremities in knee flexors
      and extensors and also at flexor/extensor ratio of the same extremity. Young
      track and field athletes exhibit strength imbalances that could reduce their
      athletic performance, and specific strength training for the weak extremity may
      be needed.

PMID- 21869633
TI  - Validation of the Cosmed Fitmate for prediction of maximal oxygen consumption.
AB  - The main purpose of this study was to assess the validity of the Cosmed Fitmate
      (FM) for the prediction of maximal oxygen consumption (VO(2)max). In addition,
      this study examined whether measuring submaximal VO(2), rather than predicting
      it, can improve upon the prediction of VO(2)max. Participants for the study were
      48 young to middle-age adults (32 men, 16 women), with a mean age of 31 yr. Each
      participant completed a submaximal and maximal treadmill test on 2 separate
      occasions. During the submaximal test, VO(2)max was predicted using the FM. This
      device extrapolates the linear regression relating heart rate (HR) and measured
      VO(2) at submaximal work rates to age-predicted maximum HR (HR = 220 - age). The
      criterion measure was obtained using a graded, maximal treadmill test, with VO(2)
      measured by the Douglas bag (DB) method. There was no significant difference
      between VO(2)max predicted by the FM and VO(2)max measured by the DB method. The
      results of this study showed that a strong positive correlation (r = 0.897)
      existed between VO(2)max predicted by the FM and VO(2)max measured by the DB
      method, with a standard error of the estimate (SEE) = 3.97 ml.kg(-1).min(-1).
      There was a significant difference in VO(2)max predicted by the American College
      of Sports Medicine (ACSM) metabolic equations and VO(2)max measured by the DB
      method (p = 0.01). The correlation between these variables was r = 0.758 (SEE =
      5.26 ml.kg(-1).min(-1)). These findings indicate that a small, portable, and easy
      to-use metabolic system provides valid estimates of VO(2)max, and improves upon
      predictive accuracy, compared to using generalized ACSM metabolic equations.

PMID- 21869634
TI  - The influence of resistance training on patients with metabolic syndrome-
      significance of changes in muscle fiber size and muscle fiber distribution.
AB  - People who are afflicted with "metabolic syndrome" exhibit multiple coronary
      disease risk factors such as insulin resistance, hypertension, hyperlipidemia, or
      obesity. Twenty-six volunteers (13 women and 13 men) with such disease risk
      factors (56 +/- 5 years) participated in a 14-week resistance training program.
      Given the fact that resistance training may improve cardiometabolic parameters,
      the fasting total cholesterol, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), triglycerides, insulin, glucose value, homeostatic model
      assessment (HOMA) index, and blood pressure and body mass index (BMI) were
      measured before and after the training intervention. In addition, muscle biopsies
      from the vastus lateralis muscle of 11 of the men and 5 of the women were
      analyzed to determine whether changes in the muscle morphology influence the
      cardiometabolic parameters. Resistance training resulted in a significant
      increase in fasting HDL for the entire group (from 44.35 +/- 9.43 to 48.57 +/-
      10.96 mg.dl(-1), p = 0.016). No other blood parameter changed significantly. No
      change was observed in the HOMA index, blood pressure, or BMI. The muscle fiber
      type distribution did not change, but a significant hypertrophy of muscle fibers
      was evident (an increase of the ellipse minor axis of 67.3 +/- 16.6 to 72.1 +/-
      12.3 MUm, p = 0.004). Moderate intensity resistance training, as was performed in
      our study, induces hypertrophic impulses but does not seem to have a clear
      positive influence on cardiometabolic risk factors. However, 2 sessions of
      moderate intensity resistance training per week can enhance the fasting HDL
      cholesterol in middle-aged subjects.

PMID- 21869635
TI  - Effects of regular heel-raise training aimed at the soleus muscle on dynamic
      balance associated with arm movement in elderly women.
AB  - The effects of low-intensity muscle training with heel-raises on dynamic balance
      associated with bilateral arm flexion were investigated in postmenopausal elderly
      women. Twenty-six elderly women were evenly grouped into training and control
      groups. Training group subjects performed 100 heel raises per day for 2 months.
      The training was aimed at hypertrophy of the soleus muscle, which has a
      relatively high proportion (ca. 90%) of slow-twitch muscle fibers and is one of
      the main postural muscles. Dynamic balance was measured while arm flexion was
      performed in response to a visual stimulus (simple-reaction condition) or at the
      subjects' own pace (own-timing condition). The following parameters were compared
      before and after the training period: plantar flexion strength, thicknesses of
      the gastrocnemius and soleus (by ultrasound), reaction time of the anterior
      deltoid in the simple-reaction condition, activation onset timing of postural
      muscles with respect to the deltoid, movement angles of ankle and hip joints, and
      postural fluctuation. In the training group only, the following training-related
      effects were demonstrated: (a) increase in plantar flexor strength and thickness
      of the soleus, (b) shortening of the deltoid reaction time, (c) earlier
      activation of the erector spinae in the simple-reaction condition and the soleus
      in the own-timing condition, and (d) increase in ankle movement in the own-timing
      condition and a decrease in postural fluctuation. This heel-raise training in the
      elderly can increase soleus thickness within the triceps surae and improve
      postural control modality and stability that are effectively contributed to by
      the leg muscle. This training consists of a low-intensity exercise that requires
      neither special machines nor a specific environment and can be performed safely
      for all old-aged groups.

PMID- 21869636
TI  - Effects of balance training using wobble boards in the elderly.
AB  - Few studies have examined balance training of elderly people using wobble boards.
      This study assessed the effects of wobble board balance training on physical
      function in institutionalized elderly people. This study examined 23 subjects
      (age 84.2 +/- 5.9 years) who lived in a nursing home. The exercise program for
      the training group comprised balance training standing on a wobble board for 9
      weeks, twice a week. In all, 11 training group subjects and 11 control group
      subjects completed this study. After 9 weeks, standing time on a wobble board,
      standing time on a balance mat, and maximum displacement distance of anterior
      posterior center of pressure in the training group were significantly greater
      than those of the control group. Frequency analysis revealed that the power
      spectrum in 0.1-0.2 Hz significantly increased in the training group. These
      results suggest that wobble board training is effective for elderly people to
      improve their standing balance, by which they frequently control their center of
      gravity and maintain a standing posture on unstable surface conditions.

PMID- 21869637
TI  - More treatment options for overactive bladder in postmenopausal women.

PMID- 21869642
TI  - Pectoralis major to scapula transfer for patients with serratus anterior palsy.
AB  - Serratus anterior palsy can be a very disabling condition. However, not much has
      been written about many other upper limb palsies and the surgical approaches for
      them. In contrast, not much has been published about this particular muscle
      palsy. Most investigators engaged in the treatment of peripheral nerve palsies
      are focused on the restoration of elbow flexion/extension and shoulder
      abduction/external rotation. Nevertheless, scapulothoracic stability is of utmost
      importance for shoulder function inasmuch as it offers a stable base for arm
      motion--mostly forward flexion. As a result, serratus anterior palsy leads to
      loss of strength, range of motion, and pain due to fatigue of synergistic muscles
      -an issue disabling enough to warrant surgical intervention. Many investigators
      have suggested a variety of techniques including muscle transfers, fascial
      slings, or scapulothoracic fusion. The last option leads to obvious limitations
      in the final range of motion and should be avoided in young high-demand patients.
      Fascial slings have a tendency to attenuate over time.

PMID- 21869643
TI  - New technique for humerus shaft fracture retrograde intramedullary nailing.
AB  - Humeral shaft fracture intramedullary nailing is less invasive than plates and
      screws. Antegrade technique has postoperative shoulder pain, increased rehab
      time, and frequent reoperation for rod removal. Published retrograde technique is
      not collinear with the shaft, has insertion site fractures (5% to 15%), and
      radial nerve palsies (5%). Our retrograde technique is collinear with the humerus
      shaft, simpler, and decreases operative fracture risk. The supine patient's elbow
      is fully flexed. A guide pin is inserted through the triceps tendon to the
      olecranon fossa roof, aligned with the humerus shaft, and drilled thought the
      cortex followed by the 6.5 mm cannulated drill through a small triceps splitting
      incision. The guide pin is passed along the humerus shaft and across the
      fracture. A small incision is made to identify and protect the radial nerve
      during reduction, reaming, and rod insertion. Flexible reamers are used and the
      nail placed and locked at least distally to prevent distal migration. An
      institutional review broad approved retrospective review of Louisiana State
      University Health Sciences Center adult humeral shaft fractures with retrograde
      technique from 1999 to January of 2009 was carried out. Sixteen patients were
      treated without perioperative fracture or nerve palsy.

PMID- 21869644
TI  - Experience with distal finger replantation: a 20-year retrospective study from a
      major trauma center.
AB  - BACKGROUND AND AIM: More than 40 years has passed since the first successfu0l
      replantation and thousands of fingers have been salvaged. We present our
      experience with distal finger replantation during 20 years of surgery. From 1990
      to 2010, 420 replantations were performed; 64 of 420 cases were distal finger
      replantations. We discuss the indications, techniques, and outcomes of these
      difficult cases. METHOD: The records of 64 patients were reviewed and the
      demographics, methods of replantation, success rates, and complications were
      evaluated. Bone shortening was performed and fixation method in this zone was
      mostly pin fixation. The "Bench Technique" for the amputated part consisted of
      preparing the artery, vein, and nerve. In zones 1 and 2a, the veins are volar and
      when incising the skin for dissection, utmost care was taken to save the volar
      delicate veins and prepare them for outflow. When there was no vein found,
      dissection was toward finding 2 arteries, 1 for inflow and 1 for outflow.
      Medicinal leeches were used during the first 10 years. Chemical leeching was used
      thereafter. RESULTS: Our patients were mostly young male workers and from the
      industrial sector. Our success rate of 87% was similar to the current literature.
      The overall complication rate from minor wound infection was 35% and total finger
      loss was 13%. Medicinal leeches had minimal satisfactory results. Chemical
      leeching was more effective. CONCLUSIONS: Our 20-year experience with distal
      finger replantation showed a success rate of 87%. On account of cultural beliefs
      amputation is not tolerated well in Eastern cultures. Thus, a high rate of single
      finger replantations is seen. The success rate is similar to that of the
      literature and cosmetic results are far superior to replantation in other zones.

PMID- 21869645
TI  - Treatment of traumatic degloving injuries of the fingers and hand: introducing
      the "compartmented abdominal flap".
AB  - BACKGROUND: Degloving injury of the hand and fingers is one of the most severe
      and debilitating hand injuries and an operation of choice is yet to be found. In
      this study, we introduce a modified abdominal flap, the "compartmented abdominal
      flap," for coverage of degloving injuries of the fingers and hand. The flaps
      reported up to now are diverse, and 2 or even 3 flaps in 1 session have been used
      to cover the hand and fingers. Often, the flaps used have mismatching colors and
      the donor defect is huge when 2 large flaps are used in 1 setting. In this study,
      we present a 1-flap solution to treat degloving injuries of the hand and fingers.
      METHOD: The compartmented abdominal flap was used in 6 patients with different
      hand and/or finger degloving injuries, which were covered by a 1-flap procedure.
      The single flap is designed in 2 layers: the flap that is an abdominal flap is
      elevated as usual and at the next stage of dissection, we create a separate
      compartment for each finger in the superficial fatty layer of the skin flap
      making pockets that encircle each finger separately. An external fixator device
      is placed to hold the fingers in their respective pockets. The flap is severed in
      3 to 4 weeks time in a serial manner. The volar surface of the fingers, which is
      covered by fatty tissues by then, is skin grafted at a later date. RESULTS: All
      the flaps survived and the contour of the hand and sensation was superior to the
      earlier flaps reported in the literature and in our earlier patients. The grasp
      and pinch function is better owing to the adherence of tissues to the volar
      surfaces of the fingers. The slippery feel of flaps over the volar surfaces of
      the fingers in handling objects is not felt or seen. CONCLUSIONS: The
      "compartmented abdominal flap" is a modification of the routine abdominal flap
      for degloving injury of the hand and fingers. The flap is designed in 2 layers: 1
      layer is to cover the dorsum of the hand and the other is created in the fatty
      layer in separate compartments for each finger. At a later date and after flap
      separation, the raw volar surface is left to granulate and is then covered by a
      split thickness skin graft.

PMID- 21869646
TI  - Paratricipital-triceps splitting "two-window" approach for distal humerus
      fractures.
AB  - Commonly, distal transcondylar and intra-articular distal humerus fractures are
      treated through a transolecranon approach. Other options for exposure, open
      reduction, and internal fixation exist to prevent the reported complications of
      olecranon osteotomy. The technique of triceps sparing access, as it has been
      reported before by others, allow adequate exposure in most of distal humerus
      fractures except for multifragmentary, mainly intra-articular types. We
      demonstrate the technique of the "two-window" approach, which combines a
      paratricipital posteromedial access with splitting the triceps lateral to the
      triceps tendon. Through a posteromedial incision, all surfaces of the distal
      humerus were accessed without muscle detachment from the olecranon. This approach
      does not compromise the ligamentous joint stability. In addition, the stabilizing
      effect of the anconeus muscle is not impaired because continuity with the lateral
      portion of the triceps is preserved, and denervation is avoided. It is extensile
      and provides adequate exposure of articular fracture comminution with the added
      advantage of the intact olecranon as a template for reduction. However, because
      the triceps is still in continuity it permits conversion to a transolecranon
      approach as necessary. The two-window approach is our preferred approach for all
      distal humerus fractures inclusively C3 fractures according to the ASIF/AO
      classification, except for complex volar shear fractures.

PMID- 21869647
TI  - Novel wire external fixation technique for proximal phalanx pilon fractures:
      technique and 2 case reports.
AB  - Unstable, severely comminuted fractures of the base of the proximal phalanx are
      often difficult to treat. We have been treating pilon-type fractures about the
      metacarpophalangeal joint using a novel external fixation technique with success.
      We present 2 examples of comminuted base of proximal phalanx fractures were
      treated successfully using the distraction external fixation with excellent
      outcomes. We believe that our technique is easily reproducible, relatively
      inexpensive, facilitates wound care, and enables early mobilization.

PMID- 21869648
TI  - Dorsal decubitus positioning: a novel method to harvest the latissimus dorsi flap
      for massive upper extremity defect reconstruction.
AB  - The latissimus dorsi, whether taken as a muscle or with a skin paddle, is one of
      the most useful flaps in the reconstructive surgeon's arsenal. With its
      predictable type V vascular pedicle, this broad muscle can be elevated on its
      dominant thoracodorsal pedicle or used in a reverse manner on its secondary
      thoracic and lumbar perforators. Traditionally harvested in a lateral decubitus
      position, over the last 10 years we have chosen to elevate this muscle in a
      dorsal decubitus position, enabling 2 surgical teams to operate simultaneously.
      With only one cushion placed along the vertebral column between the scapulas,
      each element of the subscapular system, including scapular bone, can be used to
      reconstruct complex upper limb defects. A vertical incision in front of the
      anterior axillary line is performed to identify the anterior border of the
      muscle, followed by a dissection in the submuscular plane to reveal the
      thoracodorsal pedicle and its branches. When a more complex chimeric flap is
      required, scapular bone, serratus muscle, and scapular or parascapular
      fasciocutaneous flaps are all available. To achieve the longest length possible,
      the pedicle can be isolated from the axillary vessels. The most common
      complications are related to donor site, with seroma and delayed wound healing
      being the most prevalent. Complaints of shoulder pain and functional disability
      were rare and mostly encountered in the first 2 weeks postoperatively.

PMID- 21869649
TI  - Locking flexible nails for diaphyseal humeral fractures in the multiply injured
      patient: a preliminary study.
AB  - Multiply injured patients are sometimes treated with standard intramedullary
      nails for diaphyseal humeral fractures. We evaluated the use of the Synthes
      titanium locked flexible nail in 43 multiply injured patients (average injury
      severity score, 35.2) assessing time to union, nonunion rate, shoulder and elbow
      pain, and range of motion. Twenty-seven patients underwent antegrade insertion,
      and 16 underwent retrograde insertion. An increase in union rate was noted with
      antegrade (93%) versus retrograde (69%) insertion, without statistically
      significant difference in shoulder and elbow pain or range of motion. We
      recommend the locking flexible humeral nail with antegrade insertion for multiply
      injured patients with large soft-tissue damage or severe comminution that renders
      plate fixation difficult.

PMID- 21869650
TI  - Hemilateral band technique for reconstructing gap defects in the terminal slip of
      the extensor tendon.
AB  - INTRODUCTION: Injuries to extensor tendon are a common problem seen by hand
      surgeons. Most often, these injuries can be primarily repaired. On occasion,
      however, the injury may lead to an actual substance loss in the extensor tendon,
      precluding primary approximation of the cut ends. The hemilateral band technique
      provides a solution to this problem. METHODS: The hemilateral band technique
      involves creation of a new terminal slip to bridge gaps in the extensor tendon
      using half of each lateral band in the finger. This study included patients with
      extensor tendon injury in zone I. At final follow-up, the available range of
      motion at the distal interphalangeal joint was recorded. RESULTS: Six patients
      were operated using the hemilateral band technique from 2007 to 2009. All
      patients had extensor tendon substance loss with average gap of 12 mm (5 to 20
      mm). At final follow-up, which averaged 14 months, all patients had a good
      outcome with an average motion arc of 37 degrees. No patient showed loss of
      intrinsic function at the proximal interphalangeal joint because of harvesting
      half of each lateral band. CONCLUSIONS: The hemilateral band technique is an
      effective method for reconstructing a gap deficiency in the terminal slip of the
      extensor tendon of a finger.

PMID- 21869651
TI  - Innovative nerve approximator from external fixator: a quick fix solution.
AB  - The outcome of primary and secondary neurorrhaphy depends on the technical
      precision followed during the procedure. The aim of the surgery is to establish
      near-anatomic coaptation and to maintain it without tension at the anastomotic
      site. A nerve approximator can aid in peripheral neurorrhaphy with optimal
      tension at the anastomotic site and better maintenance of coaptation of
      fascicles, but their use is limited because of the high price of the commercially
      available ones. We describe a simple and inexpensive nerve approximator that can
      be prepared any time, and according to the need using the universal mini external
      fixator system. This fixator system is almost always available in an orthopedic
      and hand operation theater. It is an extremely handy, inexpensive, atraumatic,
      and user-friendly nerve approximator that can be used clinically to aid and
      augment the final results of peripheral neurorrhaphy. Its use can also be
      extrapolated for simulated tendon and nerve repair during microvascular
      laboratory training.

PMID- 21869652
TI  - New technique of imaging and treatment of pediatric supracondylar humeral
      fracture without moving the injured limb.
AB  - The management of closed, displaced supracondylar fracture of humerus in children
      can be divided into 3 stages. In stage 1 closed reduction is achieved whose
      acceptability is confirmed, on table, in stage 2 using an image intensifier. This
      reduction is maintained in stage 3 by immobilization in slab/cast or by
      percutaneous Kirschner wire fixation. Although enough literature for proper
      technique in stage 1 and stage 3 are available, there are certain practical
      problems encountered in the equally important stage 2, which needs a closer look.
      Most of the C-arm compatible tables have their metallic base toward the head end
      of the table with metal bar on the sides for additional attachments. These
      interfere with the rotation of the image intensifier and also with the quality of
      the image obtained. As a result, to obtain lateral image many surgeons rotate the
      fractured upper limb instead of the C arm. This practice is unacceptable, as
      rotating the fractured limb cannot only add to the injury but it can also cause
      loss of reduction. Similarly, many surgeons strongly condemn using the image
      intensifier as an operating table. We are proposing a new surgeon and anesthetist
      friendly method of positioning the patient in which both anteroposterior and
      lateral views can be obtained without moving the fractured upper limb. In
      addition, if required the surgeon can proceed to open reduction without the need
      to reposition or re drape the patient.

PMID- 21869653
TI  - An approach to the supraclavicular and infraclavicular aspects of the brachial
      plexus.
AB  - The surgical approach to the brachial plexus is of great importance during
      surgery for brachial plexus injuries--obstetric or traumatic. A number of
      different approaches have been described over the years for these injuries, with
      each 1 having its own advantages and disadvantages. We describe a novel approach
      to the supra-clavicular and infra-clavicular aspects of the brachial plexus,
      which has been used by senior author successfully for the past 15 years. It
      involves creation of 2 windows, 1 above and 1 below the clavicle in case of adult
      traumatic plexus injuries. A slight variation of joining the 2 incisions and
      creation of a laterally based cervicopectoral flap is used for obstetric brachial
      plexus injuries along with the use of clavicular osteotomy. The advantages of
      this approach are that it gives rapid access to the brachial plexus; wide
      exposure can be obtained for all regions of the plexus and donor nerves such as
      the spinal accessory nerve can be harvested in the same incision.

PMID- 21869654
TI  - Perspective: Serious play: teaching medical skills with improvisational theater
      techniques.
AB  - The physician-patient encounter may be structured, but it is never scripted;
      every physician-patient interaction is to some degree improvised. Both physicians
      and improvisers must prepare for unpredictability, and the surprising and
      unrecognized overlap between improvisational theater and medical training and
      medical practice led the author to develop a seminar that tailors improvisational
      skills to physician needs, teaching communication, professionalism, and other
      medical skills through an approach she calls "medical improv." The author
      observes that there is no example of this teaching strategy as a recurring part
      of a medical school curriculum reported in the literature, and she describes the
      contributions medical improv can make to physician skills. The author reports on
      medical students' positive response to the medical improv seminar she has taught
      at Northwestern University Feinberg School of Medicine since 2002: 95% of
      students anonymously evaluating the seminar from 2002 to 2010 agreed with the
      statement, "Studying improv could make me a better doctor," and 100% agreed with
      the statement, "I would recommend this class to other medical students." The
      author proposes a medical improv teaching model that other medical schools and
      hospitals could adapt and adopt.

PMID- 21869655
TI  - "Teaching as a Competency": competencies for medical educators.
AB  - Most medical faculty receive little or no training about how to be effective
      teachers, even when they assume major educational leadership roles. To identify
      the competencies required of an effective teacher in medical education, the
      authors developed a comprehensive conceptual model. After conducting a literature
      search, the authors met at a two-day conference (2006) with 16 medical and
      nonmedical educators from 10 different U.S. and Canadian organizations and
      developed an initial draft of the "Teaching as a Competency" conceptual model.
      Conference participants used the physician competencies (from the Accreditation
      Council for Graduate Medical Education [ACGME]) and the roles (from the Royal
      College's Canadian Medical Education Directives for Specialists [CanMEDS]) to
      define critical skills for medical educators. The authors then refined this
      initial framework through national/regional conference presentations (2007,
      2008), an additional literature review, and expert input. Four core values
      grounded this framework: learner engagement, learner-centeredness, adaptability,
      and self-reflection. The authors identified six core competencies, based on the
      ACGME competencies framework: medical (or content) knowledge; learner-
      centeredness; interpersonal and communication skills; professionalism and role
      modeling; practice-based reflection; and systems-based practice. They also
      included four specialized competencies for educators with additional programmatic
      roles: program design/implementation, evaluation/scholarship, leadership, and
      mentorship. The authors then cross-referenced the competencies with educator
      roles, drawing from CanMEDS, to recognize role-specific skills. The authors have
      explored their framework's strengths, limitations, and applications, which
      include targeted faculty development, evaluation, and resource allocation. The
      Teaching as a Competency framework promotes a culture of effective teaching and
      learning.

PMID- 21869656
TI  - Developing interdisciplinary centers in aging: learning from the RAND/Hartford
      Building Interdisciplinary Geriatric Health Care Research Centers initiative.
AB  - The rising number of older patients with complex, often chronic conditions
      presents challenges in service delivery and social organization. Addressing the
      complexity of multiple interacting chronic conditions and devoting time for
      extensive interaction with elderly patients requires an interdisciplinary team.
      The "Building Interdisciplinary Geriatric Health Care Research Centers"
      initiative was designed to establish geriatric research centers that would bring
      together interdisciplinary teams of health professionals who would integrate
      concepts, methods, and practices across disciplines. The directors of the centers
      planned and conducted activities (e.g., seminars, Wikis, and mentoring) to
      develop infrastructure, to conduct collaborative research projects, and to
      support junior faculty career development. The activities in these areas led to a
      number of grant submissions and awards, to manuscript acceptances and conference
      presentations, and to career advances for junior faculty members. Overall, the
      centers' directors found that building interdisciplinary research capabilities
      takes time, attention, and support. External grant funding helped to create
      centers that, through infrastructure and activities, brought together individuals
      from a wide range of disciplines who had common interests and then helped these
      individuals collaborate to develop new projects or build on existing efforts.
      Through their infrastructure, collaborative research, and career development
      activities, the centers changed the approach to interdisciplinary research.

PMID- 21869657
TI  - From contemporary art to core clinical skills: observation, interpretation, and
      meaning-making in a complex environment.
AB  - Many medical schools have incorporated experiences with representational or
      figurative art into the curriculum in an effort to improve learners' powers of
      observation, visual diagnostic skills, and pattern recognition skills or to
      enhance communication skills, foster teamwork, and/or improve empathy. The Keck
      School of Medicine of the University of Southern California has partnered with
      Los Angeles' Museum of Contemporary Art to design an educational experience with
      the goal of honing students' abilities to observe, describe, and interpret
      complex information. The authors discovered that through a constructivist
      approach to viewing and discussing nonrepresentational, contemporary art,
      students were able not only to apply their observational and interpretive skills
      in a safe, nonclinical setting but also to accept the facts that ambiguity is
      inherent to art, life, and clinical experience and that there can be more than
      one answer to many questions. This intervention, entailing extensive guided
      inquiry, collaborative thinking, and process work, has allowed students and
      faculty to reflect on the parallel processes at work in clinical practice and art
      interpretation. In patient encounters, physicians (and physicians-in-training)
      begin with attention and observation, continue with multiple interpretations of
      that which they observe, move to sorting through often ambiguous evidence,
      proceed to collaboration within a community of observers, and finally move to
      consensus and direction for action. In the worlds of both art and medicine,
      individuals imagine experiences beyond their own and test hypotheses by
      integrating their own prior knowledge and intuition and by comparing their
      evidence with that of others.

PMID- 21869658
TI  - Art Rounds: teaching interprofessional students visual thinking strategies at one
      school.
AB  - PURPOSE: The Art Rounds program uses visual thinking strategies (VTS) to teach
      visual observation skills to medical and nursing students at the University of
      Texas Health Science Center San Antonio. This study's goal was to evaluate
      whether students' exposure to VTS would improve their physical observation
      skills, increase tolerance for ambiguity, and increase interest in learning
      communication skills. METHOD: In January 2010, 32 students attended three, 90
      minute sessions at which they observed and commented on three pieces of art in
      small groups led by museum educators. Pre and posttest evaluations included
      Geller and colleagues' version of Budner's Tolerance of Ambiguity Scale, the
      Communication Skills Attitudes Scale, and free responses to art and patient
      images. Statistical analyses compared pre and post time looking at images, number
      of words used to describe images, and number of observations made according to
      gender and discipline. RESULTS: Students significantly increased the amount of
      time they spent looking at art and patient images (P = .007), the number of words
      they used to describe art (P = .002) and patient images (P = .019), and the
      number of observations made of art (P = .000) and patient images (P = .001).
      Females increased the time spent observing significantly more than did males (P =
      .011). Students significantly increased their tolerance for ambiguity (P = .033)
      and positive views toward health care professional communication skills (P =
      .001). CONCLUSIONS: The authors speculate that these improved skills may help in
      patient care and interprofessional team interactions.

PMID- 21869659
TI  - Anticipatory guidance as a principle of faculty development: managing transition
      and change.
AB  - Although one cannot anticipate every individual's unique responses to the
      transitions and changes that regularly occur in academic medicine, a department
      wide faculty development program, based on predictable transition points and
      supporting faculty at all levels, can minimize such negative responses to change
      as stress and burnout. In 2007, the authors implemented a new, formal faculty
      development program in the pediatrics department built on the principle of
      anticipatory guidance, defined as providing guidance in anticipation of future
      academic events. The primary components of the program are mentoring committees
      for individual junior faculty, group leadership development and teaching forums
      for midlevel faculty, and events that focus on life and career changes for senior
      faculty. Other department-wide activities augment the program, including review
      of grant submissions, annual review by a senior faculty committee of the progress
      of National Institutes of Health mentored research (K-) awardees, women faculty
      luncheons, and discussions about faculty development at regular faculty meetings.
      The department's faculty also participate in the University of Rochester Medical
      Center's active faculty development program. Feedback on the faculty development
      program has been constructive and mainly positive and will serve to guide the
      continuing evolution of the program.

PMID- 21869660
TI  - Seeking balance: the complexity of choice-making among academic surgeons.
AB  - PURPOSE: This study describes the experiences of academic surgeons in seeking a
      balance between their personal and professional lives. METHOD: This
      phenomenological study, conducted in 2009-2010 at the University of Western
      Ontario, used in-depth individual semistructured interviews to explore the ideas,
      perceptions, and experiences of 17 recently recruited academic surgeons (nine
      women/eight men) about seeking balance between their personal and professional
      lives. All the interviews were audiotaped and transcribed verbatim. The data
      analysis was both iterative and interpretative. RESULTS: All the participants
      expressed a passion and commitment to academic surgery, but their stories
      revealed the complexity of making choices in seeking a balance between their
      personal and professional lives. This process of making choices was filtered
      through influential values in their lives, which in turn determined how they set
      boundaries to protect their personal and family time from the demands of their
      professional obligations. Intertwined in this process were the trade-offs they
      had to make in order to seek balance. Some choices, boundary-setting strategies,
      and trade-offs were dictated by gender. Finally, the process of making choices
      was not static; instead, the data revealed how it was both dynamic and cyclical,
      requiring reexamination over the life cycle, as well as their career trajectory.
      Thus, seeking a balance was an ever-changing process. CONCLUSIONS: Understanding
      how members of an academic department of surgery navigate the balance between
      their personal and professional worlds may provide new insights for other
      disciplines seeking to enhance the development of the next generation of
      academics.

PMID- 21869661
TI  - The incidence and predictors of job burnout in first-year internal medicine
      residents: a five-institution study.
AB  - PURPOSE: Job burnout is prevalent among U.S. internal medicine (IM) residents and
      may lead to depression, suboptimal patient care, and medical errors. This study
      sought to identify factors predicting new burnout to better identify at-risk
      residents. METHOD: The authors administered surveys to first-year IM residents at
      five institutions twice between June 2008 and June 2009, linking individual pre-
      and postresponses. Surveys measured job burnout, sleepiness, personality traits,
      and other characteristics. Burnout was defined using the most commonly identified
      definition and another stricter definition. RESULTS: Of 263 eligible residents,
      185 (70%) completed both surveys. Among 114 residents who began free of burnout
      and completed both surveys, 86 (75%) developed burnout, with no differences
      across institutions. They were significantly more likely to report a disorganized
      personality style (9 versus 0; 11% versus 0%; P = .019) and less likely to report
      receiving regular performance feedback (34 versus 13; 63% versus 87%; P = .057).
      Using a stricter definition, 50% (78/156) of residents developed burnout. They
      were less likely to plan to pursue subspecialty training (49 versus 63; 78%
      versus 93%; P = .016) or have a calm personality style (59 versus 70; 77% versus
      90%; P = .029). There were no significant associations between burnout incidence
      and duty hours, clinical rotation, demographics, social supports, loan debt, or
      psychiatric history. CONCLUSIONS: This study identified a high burnout incidence.
      The associations observed between burnout incidence and personality style, lack
      of feedback, and career choice uncertainty may inform interventions to prevent
      burnout and associated hazards.

PMID- 21869662
TI  - Difficult issues in mentoring: recommendations on making the "undiscussable"
      discussable.
AB  - Many mentoring relationships do not reach fruition because the individuals fail
      to bridge a critical difference. When a difference prevents a learning
      partnership from achieving its potential, the loss is multidimensional for the
      individuals and the institution--wasting opportunities for the fostering of
      current and future talent. Insights into when such impasses are likely to arise
      may help both mentors and mentees address what feels "undiscussable." The authors
      offer numerous examples of how differences related to ethnicity, language,
      gender, and generation may interfere with the development of mentoring
      relationships. Next, the authors offer recommendations on preparing for and
      handling difficult conversations, including creating safety, noticing assumptions
      and emotions, and raising sensitive issues. Virtually all faculty can become more
      effective at communicating across differences and addressing difficulties that
      prevent mentoring relationships from achieving their potential. The pay-offs for
      these efforts are indisputable: increased effect in the limited time available
      for mentoring, an expanded legacy of positive influence, and enhanced
      communication and leadership skills. The honing of these relational skills
      enhances the colleagueship and teamwork on which virtually all research,
      clinical, and educational enterprises depend. Academic health centers that
      systematically support mentoring enhance institutional stability, talent
      development, and leadership capacity.

PMID- 21869663
TI  - Faculty diversity programs in U.S. medical schools and characteristics associated
      with higher faculty diversity.
AB  - PURPOSE: To describe diversity programs for racial and ethnic minority faculty in
      U.S. medical schools and identify characteristics associated with higher faculty
      diversity. METHOD: The authors conducted a cross-sectional survey study of
      leaders of diversity programs at 106 U.S. MD-granting medical schools in 2010.
      Main outcome measures included African American and Latino faculty
      representation, with correlations to diversity program characteristics, minority
      medical student representation, and state demographics. RESULTS: Responses were
      obtained from 82 of the 106 institutions (77.4%). The majority of the respondents
      were deans, associate and assistant deans (68.3%), members of minority
      ethnic/racial background (65.9% African American, 14.7% Latino), and women
      (63.4%). The average time in the current position was 6.7 years, with
      approximately 50% effort devoted to the diversity program. Most programs targeted
      medical trainees and faculty (63.4%). A majority of programs received monetary
      support from their institutions (82.9%). In bivariate analysis, none of the
      program characteristics measured were associated with higher than the mean
      minority faculty representation in 2008 (3% African American and 4.2% Latino
      faculty). However, minority state demographics in 2008, and proportion of
      minority medical students a decade earlier, were significantly associated with
      minority faculty representation. CONCLUSIONS: Medical student diversity 10 years
      earlier was the strongest modifiable factor associated with faculty diversity.
      Our results support intervening early to strengthen the minority medical student
      pipeline to improve faculty diversity. Schools located in states with low
      minority representation may need to commit additional effort to realize
      institutional diversity.

PMID- 21869664
TI  - Perspective: A new model of leadership performance in health care.
AB  - Current leadership models are based largely on concepts and explanations, which
      provide limited access to the being and actions of an effective leader in health
      care. Rather than teaching leadership from a theoretical vantage point, the
      ontological perspective teaches leadership as it is lived and experienced. When
      one exercises leadership "as lived," concurrently informed by theories, one
      performs at one's best. A distinctive feature of the ontological approach resides
      in its capacity to disclose human ways of being and acting that limit our freedom
      to lead effectively as our natural self-expression. Ontological leadership
      maintains that our worldviews and mental maps affect the way we lead and are
      shaped by and accessible through language--hence, to lead more effectively,
      mastery of a new conversational domain of leadership is required. This emerging
      model of leadership performance reveals that (1) our actions as leaders are
      correlated with the way in which the leadership situation we are dealing with
      occurs for us, and (2) this "occurring" is shaped by the context we bring to that
      situation. Master leaders use language to recontextualize their leadership
      challenges so that their naturally correlated ways of being and acting can
      emerge, resulting in effective leadership. When leaders linguistically unveil
      limiting contexts, they are freed up to create new contexts that shift the way
      leadership challenges occur for them. This provides leaders--physicians,
      scientists, educators, executives--with new opportunity sets (previously
      unavailable) for exercising exemplary leadership. The ontological approach to
      leadership offers a powerful framework for tackling health care's toughest
      challenges.

PMID- 21869665
TI  - Medical students' experiences of professional lapses and patient rights abuses in
      a South African health sciences faculty.
AB  - PURPOSE: To elicit South African medical students' experiences of witnessing
      patient rights abuses and professional lapses during their clinical training in
      order to inform an appropriate and effective response. METHOD: During June and
      July 2009 at the University of Cape Town Faculty of Health Sciences, the authors
      surveyed 223 fourth-, fifth-, and sixth-year medical students in selected
      clinical rotations concerning abuses they had observed. Volunteers were later
      interviewed individually. The authors coded interview transcripts for key themes
      using a constant-comparative grounded theory approach. RESULTS: Of 223 students
      surveyed, 183 (82%) responded, 130 (71%) of whom reported witnessing patient
      rights abuses and professional lapses, including physical abuse (38%), verbal
      abuse (37%), disrespect for patients' dignity (25%), and inadequately informing
      patients about their treatment (25%). Students attributed abuse to stressed
      health workers, overburdened facilities, and disempowered patients. Most students
      who witnessed abuse (59%) did not actively respond, and 64% of survey respondents
      felt unprepared or uncertain about challenging abuses in the future. Interviews
      with 28 students yielded detailed accounts of the abuses witnessed and of
      students' emotional reactions, coping strategies, and responses. Most students
      did not report abuses; they feared reprisal or doubted it would make a
      difference. CONCLUSIONS: This study demonstrates the disjunction between what
      these students were taught about human rights and ethics and what they witnessed
      in clinical settings. The high prevalence of patient rights abuses experienced by
      these students highlights the need to align medical ethics and human rights with
      medico-legal protocols in theory and clinical practice.

PMID- 21869666
TI  - Is residents' progress on individualized learning plans related to the type of
      learning goal set?
AB  - PURPOSE: To determine the types of learning goals residents select for their
      individualized learning plans (ILPs) and the relationship between goal type and
      progress toward achieving that goal. METHOD: Pediatric and combined pediatric
      residents at 46 U.S. training programs completed a Web-based survey on ILPs in
      2008-2009, describing their most important learning goal and the goals on which
      they made the most and least progress. Using iterative inductive review,
      responses were categorized into seven types (six corresponding with the
      Accreditation Council for Graduate Medical Education general competencies).
      Descriptive statistics and regression models were used to assess the relationship
      between goal type and progress made. RESULTS: Of 1,739 eligible residents, 992
      (57%) completed the survey; 668 (38%) had previously completed an ILP and
      described their learning goals. Residents were more likely to report medical
      knowledge (MK) (53.7%) and patient care (PC) (25.9%) goals as most important and
      less likely to report professionalism (1.5%) and systems-based practice (SBP)
      (1.0%) goals as most important. Compared with progress on MK goals, residents
      reported significantly greater progress on PC (odds ratio [OR]: 2.20; 95%
      confidence interval [CI]: 1.57-3.09) and practice-based learning and improvement
      teaching (OR: 2.99; 95% CI: 1.59-5.63) goals and less progress on SBP goals (OR:
      0.16; 95% CI: 0.05-0.56). CONCLUSIONS: Residents most commonly identified MK and
      PC learning goals as the most important. Residents made more progress on goals
      related to everyday tasks, such as PC and teaching, compared with goals less
      integrated in everyday training, such as SBP.

PMID- 21869667
TI  - Emotional intelligence and stress in medical students performing surgical tasks.
AB  - PURPOSE: Poor stress management skills can compromise performance in the
      operating room, particularly in inexperienced trainees. Little is known about
      individual differences in managing stress. This study aimed to explore the
      relationship between trait emotional intelligence (EI) and objective and
      subjective measures of stress in medical students faced with unfamiliar surgical
      tasks. METHOD: Seventeen medical undergraduates completed an unfamiliar
      laparoscopic task on a simulator during January to April 2008. Subjective stress
      before, during (retrospectively), and after the task was measured using the self
      report State-Trait Anxiety Inventory. Objective stress was measured using
      continuous heart rate (HR) monitoring. Participants also completed the Trait
      Emotional Intelligence Questionnaire short form (TEIQue-SF). The authors computed
      scores for global trait EI and the TEIQue-SF four factors and carried out
      descriptive and correlational analyses. RESULTS: The highest levels of subjective
      stress were reported during the task and correlated positively with trait EI as
      well as with the trait EI factors of well-being and emotionality. Objective
      stress (mean HR) during the task was positively related to the sociability factor
      of trait EI. Higher trait EI scores were also associated with better after-task
      recovery from stress experienced during the task. CONCLUSIONS: Students with
      higher trait EI are more likely to experience stress during unfamiliar surgical
      scenarios but are also more likely to recover better compared with their lower
      trait-EI peers. Trait EI has implications for the design of effective stress
      management training tailored to individual needs and potential applications to
      surgical trainee selection and development.

PMID- 21869668
TI  - Perspective: Toward a competency framework for faculty.
AB  - Today, faculty in academic medicine face challenges in all three mission areas-
      research, education, and patient care--and require a broad set of competencies to
      survive in this changing environment. To support faculty and to design
      assessments that match new expectations, the authors argue that it is essential
      to capture the full scope of skills, knowledge, and behaviors necessary for a
      successful faculty member. Thus, it is timely to explore and define competencies
      for faculty in academic medicine. The authors describe three approaches to
      identifying faculty competencies. Each reveals diverse but overlapping sets of
      competency domains, reflecting the breadth of activities expected of today's
      faculty. To organize these competencies into a coherent framework, the authors
      propose a model based on a typology of competency. A key feature of the model is
      the division between occupational competencies, which are largely role-specific,
      and personal competencies, which are necessary for all faculty. A competency
      framework also must be developmental, to reflect the growth in skills, knowledge,
      and behaviors from trainee to expert and to allow for an individual's changing
      roles over a career. Such a competency framework will inform professional
      development activities and require assessment of competence. The generation of
      competencies also will reveal areas of faculty practice that are poorly measured,
      requiring new tools to be incorporated into existing processes of faculty
      evaluation. The authors provide general principles to guide the identification of
      a competency framework for faculty and invite the academic medicine community to
      engage in further discussion.

PMID- 21869669
TI  - Evaluating construct equivalence and criterion-related validity for repeat
      examinees on a standardized patient examination.
AB  - PURPOSE: Prior studies report large score gains for examinees who fail and later
      repeat standardized patient (SP) assessments. Although research indicates that
      score gains on SP exams cannot be attributed to memorizing previous cases, no
      studies have investigated the empirical validity of scores for repeat examinees.
      This report compares single-take and repeat examinees in terms of both internal
      (construct) validity and external (criterion-related) validity. METHOD: Data
      consisted of test scores for examinees who took the United States Medical
      Licensing Examination Step 2 Clinical Skills (CS) exam between July 16, 2007, and
      September 12, 2009. The sample included 12,090 examinees who completed Step 2 CS
      on one occasion and another 4,030 examinees who completed the exam on two
      occasions. The internal measures included four separately scored performance
      domains of the Step 2 CS examination, whereas the external measures consisted of
      scores on three written assessments of medical knowledge (Step 1, Step 2 clinical
      knowledge, and Step 3). The authors subjected the four Step 2 CS domains to
      confirmatory factor analysis and evaluated correlations between Step 2 CS scores
      and the three written assessments for single-take and repeat examinees. RESULTS:
      The factor structure for repeat examinees on their first attempt was markedly
      different from the factor structure for single-take examinees, but it became more
      similar to that for single-take examinees by their second attempt. Scores on the
      second attempt correlated more highly with all three external measures.
      CONCLUSIONS: The findings support the validity of scores for repeat examinees on
      their second attempt.

PMID- 21869670
TI  - Unsupported labeling of race as a risk factor for certain diseases in a widely
      used medical textbook.
AB  - PURPOSE: Confounding of racial, socioeconomic, and behavioral characteristics may
      lead to the misidentification of race as a risk factor for certain diseases. The
      authors evaluated the validity of attributing race as a risk factor in a widely
      used pathology textbook. METHOD: In 2009-2010, the authors searched Robbins and
      Cotran Pathologic Basis of Disease, Professional Edition (8th ed) for assertions
      that African Americans have a different disease profile than do individuals of
      other races. They evaluated the references cited in the textbook, assessing the
      quality of the sources and whether those authors controlled for confounding
      variables, such as socioeconomic status and behavioral characteristics. For
      statements that remained unconfirmed, the authors searched the literature for
      evidence supporting or contradicting the claims made in the textbook. The authors
      classified each statement from the textbook as supported, unconfirmed, or
      contradicted. RESULTS: Of the 31 relevant statements, 11 were supported by the
      literature review, 17 remained unconfirmed, and three were contradicted.
      CONCLUSIONS: About two-thirds of the assertions that different risk factors exist
      for African Americans found in a widely used pathology textbook could not be
      supported by the published literature. Failure to separate race from other
      socioeconomic and behavioral characteristics as risk factors for certain diseases
      may contribute to the misdiagnosis of patients and interfere with efforts to
      identify and remove causes of health disparities.

PMID- 21869671
TI  - Zolmitriptan induced acute coronary syndrome: a unique case.
AB  - Triptans have been used for the acute treatment of migraine headaches for many
      years. Although their use can lead to coronary vasospasm, there are very few
      reports of triptans actually leading to myocardial infarction in patients with
      normal coronaries. We hereby present a 58-year-old man who presented to the
      emergency room with chest pain. Electrocardiogram demonstrated ST segment
      depression in the inferior leads with diffuse spasm of the distal right coronary
      artery seen on angiography, which was easily reversed by intracoronary
      nitroglycerine. We believe this is the first reported case of a patient with a
      myocardial infarction after taking oral zolmitriptan in which coronary angiogram
      clearly demonstrated coronary vasospasm reversal after intracoronary
      nitroglycerine. A detailed search of the literature for reported cases of
      myocardial infarction after triptan use is also provided.

PMID- 21869672
TI  - Secondary arterial hypertension: improvements in diagnosis and management in the
      last 10 years.
AB  - The diagnosis and management of secondary hypertension has improved in the last
      decade as a result of the advances in the acknowledgment of some physiopathologic
      mechanisms and mainly by the development of new diagnostic methods. Furthermore,
      the treatment of some types of secondary hypertension may be solved by
      noninvasive techniques. Hypertension of renal and renovascular origin,
      coarctation of the aorta, primary hyperaldosteronism, and adrenal medullary
      tumors are analyzed. The main results of some relevant studies on diagnostic and
      treatment of those diseases are presented. Also, some experimental methods are
      mentioned, taking into account the possibility of clinical use in the near
      future.

PMID- 21869675
TI  - Three thousand seven hundred thirty-eight posttraumatic pulmonary emboli: a new
      look at an old disease.
AB  - OBJECTIVE: This study was undertaken to determine the current incidence of
      pulmonary embolism (PE) and its attributable mortality after injury. BACKGROUND:
      Despite compliance with prophylactic measures, PE remains a threat to postinjury
      recovery. We hypothesized that the liberal use of chest computed tomography after
      injury has resulted in an increased rate of detection of PE but that the
      mortality attributable to PE has decreased over the past decade. We also
      postulated that the risk factors for posttraumatic PE might be different from
      those for deep venous thrombosis (DVT). METHODS: We examined demographics, injury
      data, risk factors, and outcomes from patients with DVT and PE compiled in the
      recent years (2007-2009) in the National Trauma Data Bank (NTDB). For comparison,
      we used patient data entered into NTDB from 1994 to 2001. Statistical models were
      created to examine the predictors of DVT and PE and PE-related mortality.
      RESULTS: Among 888,652 patients in the current NTDB cohort, there were 9398
      episodes of DVT (1.06%) and 3738 of PE (0.42%). Although many risk factors
      overlapped, a severe chest injury (Abbreviated Injury Score >= 3) conferred a
      much higher risk of PE than DVT. When comparing results from centers that had
      contributed to both data sets, there was a more than 2-fold increase in PE
      occurrence in the current cohort (0.49% vs 0.21%, P < 0.01) but with a
      significant reduction in PE-adjusted mortality (odds ratio, 4.08 vs 2.42).
      CONCLUSIONS: The reported incidence of PE after trauma has more than doubled in
      recent years, while the PE-associated mortality has significantly decreased,
      suggesting that we are identifying a different disease entity or stage. Chest
      injuries convey a substantial risk for PE, a risk not likely to be diminished by
      leg compression devices or vena cava filters.

PMID- 21869674
TI  - The anatomic pattern of biliary atresia identified at time of Kasai
      hepatoportoenterostomy and early postoperative clearance of jaundice are
      significant predictors of transplant-free survival.
AB  - OBJECTIVE: The goals of this study were to describe the clinical and anatomic
      features of infants undergoing Kasai portoenterostomy (KPE) for biliary atresia
      (BA) and to examine associations between these parameters and outcomes. METHODS:
      Infants enrolled in the prospective Childhood Liver Disease Research and
      Education Network, who underwent KPE were studied. Patients enrolled in a
      blinded, interventional trial were excluded from survival analysis. Primary
      endpoints were successful surgical drainage (total bilirubin less than 2 mg/dL
      within the first 3 months), transplant-free survival (Kaplan-Meier), and time to
      transplant/death (Cox regression). RESULTS: KPE was performed in 244 infants (54%
      female; mean age: 65 +/- 29 days). Transplant-free survival was 53.7% and 46.7%
      at 1 and 2 years post-KPE. The risk of transplant/death was significantly lower
      in the 45.6% of patients who achieved successful bile drainage within 3 months
      post-KPE (HR: 0.08, P < 0.001). The risk of transplant/death was increased in
      patients with porta hepatis atresia (Ohi type II and III vs type I; HR: 2.03, P =
      0.030), nonpatent common bile duct (Ohi subtype: b, c, and d vs a; HR: 4.31, P =
      0.022), BA splenic malformation syndrome (HR: 1.92, P = 0.025), ascites > 20 mL
      (HR: = 1.90, P = 0.0230), nodular liver appearance compared to firm (HR: = 1.61,
      P = 0.008), and age at KPE >= 75 days (HR: 1.73, P < 0.002). Outcome was not
      associated with gestational age, gender, race, ethnicity, or extent of porta
      hepatis dissection. CONCLUSION: Anatomic pattern of BA, BASM, presence of ascites
      and nodular liver appearance at KPE, and early postoperative jaundice clearance
      are significant predictors of transplant-free survival.

PMID- 21869676
TI  - Nonintubated thoracoscopic lobectomy for lung cancer.
AB  - OBJECTIVE: To evaluate the feasibility and safety of thoracoscopic lobectomy
      without endotracheal intubation. SUMMARY BACKGROUND DATA: General anesthesia with
      single-lung ventilation is considered mandatory for thoracoscopic lobectomy for
      non-small cell lung cancer (NSCLC). Nonintubated thoracoscopic lobectomy has not
      been reported previously. METHODS: From August 2009 through June 2010, some 30
      consecutive patients with clinical stage I or II NSCLC were treated by
      nonintubated thoracoscopic lobectomy using epidural anesthesia, intrathoracic
      vagal blockade, and sedation. To evaluate the feasibility and safety of this
      novel technique, they were compared with a control group consisting of 30
      consecutive patients with clinical stage I or II NSCLC who underwent
      thoracoscopic lobectomy using intubated general anesthesia from August 2008
      through July 2009. RESULTS: Collapse of the operative lung and inhibition of
      coughing were satisfactory in the nonintubated patients, induced by spontaneous
      breathing, and vagal blockade. Three patients in the nonintubated group required
      conversion to intubated-single lung ventilation because of persistent hypoxemia,
      poor epidural anesthesia pain control, and bleeding. One patient in each group
      was converted to thoracotomy because of bleeding. The 2 groups had comparable
      anesthesia durations, surgical durations, blood loss, and numbers of dissected
      lymph nodes. Patients who underwent nonintubated surgery had lower rates of sore
      throat (6.7% vs 40.0%, P = 0.002) and earlier resumption of oral intake (mean,
      4.7 hours vs 18.8 hours, P < 0.001). Patients undergoing nonintubated surgery
      also had a trend toward better noncomplication rates (90% vs 66.7%, P = 0.057)
      and shorter postoperative hospital stays (mean, 5.9 days vs 7.1 days, P = 0.078).
      CONCLUSIONS: Nonintubated thoracoscopic lobectomy is technically feasible and is
      as safe as lobectomy performed with intubation in highly selected patients. It
      can be a valid alternative of single-lung-ventilated thoracoscopic surgery in
      managing early-stage NSCLC.

PMID- 21869677
TI  - The attributable risk of smoking on surgical complications.
AB  - OBJECTIVE: This study aimed to assess the attributable risk and potential benefit
      of smoking cessation on surgical outcomes. SUMMARY BACKGROUND DATA: Risk
      reduction with the implementation of surgical care improvement project process
      measures has been the primary focus for improving surgical outcomes. Little
      emphasis has been placed on preoperative risk factor recognition and
      intervention. METHODS: A retrospective cohort analysis of elective operations
      from 2002 to 2008 in the Veterans Affairs Surgical Quality Improvement Program
      for all surgical specialties was performed. Patients were stratified by current,
      prior, and never smokers. Adjusted risk of complication and death was calculated
      using multilevel, multivariable logistic regression. RESULTS: Of 393,794
      patients, 135,741 (34.5%) were current, 71,421 (18.1%) prior, and 186,632 (47.4%)
      never smokers. A total of 6225 pneumonias, 11,431 deep and superficial surgical
      site infections, 2040 thromboembolic events, 1338 myocardial infarctions, and
      4792 deaths occurred within 30 days of surgery. Compared with both never and
      prior smokers individually and controlled for patient and procedure risk factors,
      current smokers had significantly more postoperative pneumonia, surgical-site
      infection, and deaths (P < 0.001 for all). There was a dose-dependent increase in
      pulmonary complications based on pack-year exposure with greater than 20 pack
      years leading to a significant increase in smoking-related surgical
      complications. CONCLUSIONS: This is the first study to assess the risk of current
      versus prior smoking on surgical outcomes. Despite being younger and healthier,
      current smokers had more adverse perioperative events, particularly respiratory
      complications. Smoking cessation interventions could potentially reduce the
      occurrence and costs of adverse perioperative events.

PMID- 21869678
TI  - Caval inflow to the graft for liver transplantation in patients with diffuse
      portal vein thrombosis: a 12-year experience.
AB  - OBJECTIVE: To analyze the short- and long-term results of cavoportal anastomosis
      (CPA) and renoportal anastomosis (RPA) in 20 consecutive liver transplantation
      (LT) candidates with diffuse portal vein thrombosis (PVT). SUMMARY BACKGROUND
      DATA: Caval inflow to the graft (CIG) by CPA or RPA has been the most commonly
      used salvage technique to overcome the absolute contraindication for LT in case
      of diffuse PVT. METHODS: From 1996 to 2009, 3 patients (15%) underwent CPA and 17
      patients (85%) had an RPA during LT. In addition to routine follow-up, patients
      were specifically evaluated for signs of portal hypertension (PHT) and for
      patency of the anastomoses. The follow-up ranged from 3 months to 12 years
      (median of 4.5 years). RESULTS: : Caval inflow to the graft was feasible in all
      attempted cases. In the short term (<6 months), 35% of patients had residual PHT
      related complications (massive ascites and variceal bleeding). These resolved
      spontaneously or with endoscopic management. Three deaths occurred; none was
      related to PHT or shunt thrombosis. In the long term (>6 months), 1 death
      occurred because of recurrent variceal bleeding after RPA thrombosis. At last
      follow-up, all living patients [n = 13 (65%)] had normal liver function, no signs
      of PHT and patent anastomoses. There were no retransplantations. Graft and
      patient survival at 1, 3, and 5 years were 83%, 75%, and 60%, respectively.
      CONCLUSIONS: Caval inflow to the graft is an efficacious salvage technique with
      satisfactory long-term results, considering the spontaneous outcome in patients
      denied LT because of diffuse PVT. Adequate preoperative management of PHT and its
      associated complications is vital in obtaining good results. In the long term,
      residual PHT resolves and the liver function returns to normal.

PMID- 21869679
TI  - Aneurysmal subarachnoid hemorrhage: an update on the medical complications and
      treatments strategies seen in these patients.
AB  - PURPOSE OF REVIEW: Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating
      condition with high mortality and poor outcome among survivors. Early surgical or
      endovascular securing of the aneurysm is the norm, and management of these
      patients is precarious due to their unstable intracranial physiology and the
      severe systemic medical complications common in SAH. RECENT FINDINGS: New
      research into biomarkers and clinical factors with their association to outcome
      in SAH can help us to identify patients at risk. New evidence questions the
      benefit of broad application of the current SAH treatment mainstays, and re
      examines agents previously failing clinical trials. SUMMARY: Growing knowledge of
      the physiologic derangements associated with poor outcomes in SAH can improve our
      understanding of the widespread physiologic changes occurring with SAH and with
      further research, may provide clinicians with a direction for increasingly
      meaningful intervention. Ongoing investigation of our current therapeutics enable
      clinicians to apply them more judiciously to suitable patients, thereby enhancing
      the benefit and minimizing the complications of such treatments. Furthermore, by
      re-evaluating previously disproved treatments through the use of novel regimens
      or administration routes, promising treatment options are emerging.

PMID- 21869680
TI  - Neurologic complications of regional anesthesia.
AB  - PURPOSE OF REVIEW: Regional anesthesia is evolving rapidly and increasing in
      popularity as evidenced by the large number of publications on the topic. In this
      healthcare environment, continual assessment of the safety and efficacy of
      clinical practice is critical. Neurologic complications of regional anesthesia
      can result in disability and are feared by patients and clinicians. Ultrasound
      guidance is unique as a nerve localizing technique in terms of being able to
      image needle-nerve proximity and potentially prevent direct trauma to nerves.
      This article reviews the recent literature relevant to neurologic complications
      of regional anesthesia. RECENT FINDINGS: The incidence of intraneural injection
      during regional anesthesia is higher than previously appreciated. Defining
      intraneural injection and its significance are the subject of current debate.
      Clinical studies with small sample sizes suggest that intraneural injection may
      not necessarily be responsible for nerve injury. Inflammatory mechanisms may
      contribute to perioperative nerve injury. Ultrasound guidance has not been proven
      to reduce the incidence of nerve injury due to peripheral nerve blockade (PNB).
      Increased utilization of PNB is not associated with an increase in perioperative
      nerve injury. SUMMARY: The pathogenesis of perioperative nerve injury is complex
      with multiple potential etiologies and mechanisms. The role of intraneural
      injections as a modifiable risk factor for neurologic complications due to
      regional anesthesia remains topical. Relevant publications include studies on the
      morphology of peripheral nerves and risk of perioperative nerve injury in the
      context of both neuraxial anesthesia and PNB.

PMID- 21869681
TI  - Outcome of wrist injuries with clinical suspicion of scaphoid injury after normal
      computed tomography.
AB  - OBJECTIVES: Wrist injuries are a common presentation to emergency departments. A
      clinical pathway has recently been introduced in our institution for patients
      with clinical suspicion of a scaphoid injury, using computed tomography (CT) at 2
      weeks postinjury to rule out scaphoid fracture. However, it is not known what
      happens to patients who have a normal CT after such an injury. The aim of this
      pilot study was to assess disability after CT-negative wrist injuries. METHODS: A
      prospective questionnaire study was undertaken to assess disability in patients
      who had a normal CT after clinical suspicion of a scaphoid fracture, using the
      Patient Rated Wrist Evaluation questionnaire. Adult patients were recruited at
      their first emergency department clinic review, where a baseline questionnaire
      was completed. Follow-up questionnaires were sent 3, 6 and 12 months later. Pain
      and function were assessed on a 0-10 scale, giving a total score out of 100.
      RESULTS: Ninety-nine patients were initially recruited, of whom 72 had negative
      CT; 40 patients completed follow-up. There was a statistically significant
      reduction in pain, functional deficit and combined disability between baseline
      scores and 12-month follow-up. Overall, three (8%) patients had severe disability
      (pain and function combined), and six (15%) had moderate disability at 12 months.
      CONCLUSION: The majority of these patients recover from their injury, but a small
      proportion with normal CT scans have considerable disability 12 months after
      injury. Appropriate advice should be given to these patients to enable them to
      access further investigation and treatment.

PMID- 21869682
TI  - Comparison of endoscopic submucosal dissection and endoscopic mucosal resection
      for large colorectal tumors.
AB  - BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) is the standard procedure
      for treatment of colorectal tumors. Endoscopic submucosal dissection (ESD) can be
      performed for resection of larger tumors, but has not been studied in the
      colorectum because of technical difficulties and complications. We compared
      outcomes and complications after resection of colorectal tumors larger than 20 mm
      diameter by ESD and EMR. MATERIALS AND METHODS: We retrospectively studied 104
      colorectal tumors treated with EMR from 1995 to 2004, and 85 colorectal tumors
      treated with ESD from 2005 to 2009. We compared the tumor location, shape, size,
      procedure time, en bloc resection rate, recurrence rate, and associated
      complications between the treatments. RESULTS: Tumors treated with ESD were
      larger (31.6 +/- 9.0 vs. 25.5 +/- 6.8 mm, P<0.001), incurred a longer procedure
      time (87.2 +/- 49.7 vs. 29.4 +/- 26.1 min, P<0.001), had a higher en bloc
      resection rate [71 of 85 tumors (83.5%) vs. 50 of 104 tumors (48.1%), P<0.001],
      and had a lower recurrence rate [one of 84 tumors (1.2%) vs. 16 of 104 tumors
      (15.4%); P=0.002] compared with EMR. Perforation occurred in five (5.9%) cases
      after ESD and in none after EMR (P=0.04). Postoperative bleeding occurred in two
      (2.4%) and three (2.9%) cases after ESD and EMR (P=not significant),
      respectively. Although 11 of 16 cases with recurrence after EMR were cured by
      additional endoscopic treatment, three cases required surgery. The only
      recurrence after ESD was in one patient who developed perforation after snare
      EMR. CONCLUSION: Despite its longer procedure time and higher perforation rate,
      ESD resulted in a higher en bloc resection rate and lower recurrence rate for
      larger colorectal tumors compared with EMR.

PMID- 21869684
TI  - Sinus augmentation surgery after endoscopic sinus surgery for the treatment of
      chronic maxillary sinusitis: a case report.
AB  - Chronic sinusitis develops when the ostiomeatal complex becomes stenosed by the
      swelling of the sinus mucosa. Previously, the Caldwell-Luc method was performed
      for the treatment of chronic sinusitis. But postoperative complications, such as
      discomfort of the buccal skin and recurrence of sinusitis, frequently occurred
      after the operation. Today, endoscopic sinus surgery (ESS) has become widely used
      for the treatment of chronic sinusitis. The features of ESS allow for the
      restoration of the physical function of the sinus membrane and preservation of
      the physiological environment of the sinus. Therefore, sinus augmentation surgery
      can be safely performed at an insufficient alveolar bone height below the
      maxillary sinus when sinusitis is eliminated by the ESS. This article documents a
      patient history involving chronic sinusitis that was treated by the ESS therapy
      before sinus augmentation surgery as a pretreatment for insertion of dental
      implants.

PMID- 21869685
TI  - Placebo-controlled pilot study of ramelteon for adiposity and lipids in patients
      with schizophrenia.
AB  - OBJECTIVE: Few interventions have been successful to prevent or reverse the
      medical complications associated with antipsychotic agents in the schizophrenia
      population. In particular, no single agent can correct multiple metabolic
      abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity,
      and fat distribution. We now report a randomized placebo-controlled pilot study
      to examine the effects of ramelteon on obesity and metabolic disturbances among
      subjects with schizophrenia. METHODS: A double-blind, placebo-controlled, 8-week
      pilot trial was conducted, adding ramelteon 8 mg/d to stable outpatients with
      schizophrenia. Vital signs and anthropometric measurements, including height,
      weight, waist circumference, and body fat were assessed, and laboratory assays
      were tracked to monitor changes in metabolic markers. RESULTS: Twenty-five
      subjects were randomly assigned to treatment with study drug or placebo, and 20
      subjects were included in the final analysis. Ramelteon did not improve
      anthropometric measurements, glucose metabolism, and inflammatory markers. There
      was, however, a significant decrease in total cholesterol and ratio of
      cholesterol to high-density lipoprotein in the ramelteon group. Although the
      standard anthropometric measures did not show significant change, the dual-energy
      x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal
      and trunk areas with a moderate effect size. CONCLUSIONS: Although ramelteon
      decreased cholesterol, treatment may have to be longer than 8 weeks and with a
      higher dose for maximal effect of ramelteon for body fat and lipid changes.
      Future studies are needed for patients with schizophrenia with a larger sample
      size to fully understand ramelteon's effects on abdominal adiposity and lipids.

PMID- 21869686
TI  - The efficacy and safety of alprazolam versus other benzodiazepines in the
      treatment of panic disorder.
AB  - We performed a meta-analysis of all single- or double-blind, randomized
      controlled trials comparing alprazolam to another benzodiazepine in the treatment
      of adult patients meeting the Diagnostic and Statistical Manual of Mental
      Disorders, Third or Fourth Edition, criteria for panic disorder or agoraphobia
      with panic attacks. Eight studies met inclusion criteria, describing a total of
      at least 631 randomized patients. In the pooled results, there were no
      significant differences in efficacy between alprazolam and the comparator
      benzodiazepines on any of the prespecified outcomes: improvement in mean panic
      attack frequency (between-arm weighted mean difference of 0.6 panic attacks per
      week; 95% confidence interval [CI], -0.3 to 1.6), improvement in Hamilton Anxiety
      Rating Scale score (weighted mean difference of 0.8 points; 95% CI, -0.5 to 2.1),
      and proportion of patients free of panic attacks at the final evaluation (pooled
      relative risk, 1.1; 95% CI, 0.9-1.4). Statistical heterogeneity on prespecified
      outcomes was not eliminated by stratification on baseline anxiety level. The
      available evidence fails to demonstrate alprazolam as superior to other
      benzodiazepines for the treatment of panic disorder.

PMID- 21869687
TI  - A 1-year, open-label study assessing the safety and tolerability of vilazodone in
      patients with major depressive disorder.
AB  - Vilazodone, a selective serotonin (5-HT) reuptake inhibitor and 5-HT(1A) receptor
      partial agonist, was efficacious in two 8-week placebo-controlled studies in
      adults with major depressive disorder. This open-label, multicenter study
      assessed the long-term safety of vilazodone. Adult patients with a 17-item
      Hamilton Rating Scale for Depression score of 18 or greater received vilazodone
      according to a fixed-titration schedule to reach a dose of 40 mg/d continued up
      to 1 year. Safety assessments included adverse events (AEs), physical
      examinations, clinical chemistry, electrocardiograms, and the Changes in Sexual
      Functioning Questionnaire. Effectiveness was assessed with the Montgomery-Asberg
      Depression Rating Scale and Clinical Global Impressions scales. The safety
      population comprised 599 patients; 254 patients completed 1 year of treatment.
      The most frequent AEs were diarrhea (35.7%), nausea (31.6%), and headache
      (20.0%); greater than 90% of these AEs were mild or moderate. Adverse events
      resulting in discontinuation in more than 1% of patients were nausea (1.3%) and
      diarrhea (1.2%). There were no clinically important changes in physical
      examinations, electrocardiograms, or clinical chemistries. Mean weight increased
      by 1.7 kg (observed cases). Changes in Sexual Functioning Questionnaire mean
      scores (observed cases) improved throughout treatment for both males and females.
      Montgomery-Asberg Depression Rating Scale mean scores were 29.9 at baseline, 11.4
      at week 8, and 7.1 at week 52 (observed cases). Vilazodone 40 mg/d for 1 year was
      safe and well tolerated by adults with major depressive disorder.

PMID- 21869688
TI  - A pilot study of the efficacy and safety of paroxetine augmented with
      risperidone, valproate, buspirone, trazodone, or thyroid hormone in adult Chinese
      patients with treatment-resistant major depression.
AB  - To compare the efficacy and safety of augmenting paroxetine with risperidone,
      buspirone, valproate, trazodone, or thyroid hormone in patients with treatment
      resistant depression (TRD), 225 patients with retrospectively and/or
      prospectively identified stage II TRD were randomly assigned to receive an 8-week
      treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d (n = 45),
      sodium valproate 600 mg/d (n = 39), buspirone 30 mg/d (n = 46), trazodone 100
      mg/d (n = 47), or thyroid hormone 80 mg/d (n = 48). The primary outcome was the
      remission rate defined as the 17-item Hamilton Rating Scale for Depression score
      of 7 or less at the end of study. Secondary outcomes included remission rate
      based on the Self-rating Depression Scale score of 50 or less at the end of
      study, response rate based on 17-item Hamilton Rating Scale for Depression total
      score of 50% improvement or greater from baseline, and the change in scores of
      Clinical Global Impression-Improvement scale, the Short Form 36 Health Survey,
      and the Life Satisfaction Rating Scale. The remission rates were 26.7% for
      risperidone, 48.7% for valproate, 32.6% for buspirone, 42.6% for trazodone, and
      37.5% for thyroid hormone. There was no statistical significance among treatment
      arms in remission rates, secondary outcome measures, and adverse events.
      Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to
      paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD.
      Large-sample studies are warranted to support or refute these findings.

PMID- 21869689
TI  - Comparing the influence of dopamine D2 polymorphisms and plasma drug
      concentrations on the clinical response to risperidone.
AB  - Although several studies have reported that dopamine D2 receptor (DRD2)
      polymorphisms affect the therapeutic efficacy of antipsychotics, other studies
      have suggested that the plasma drug concentration is related to the clinical
      response. Currently, there are no definitive data regarding which factor has
      greater clinical significance. Sixty patients with acute exacerbations of
      schizophrenia received 6 mg/d of risperidone for 4 weeks. Clinical evaluations
      using the Brief Psychiatric Rating Scale and the Udvalg for Klinicke
      Undersogelser Side Effect Rating Scale were performed before and after
      administration of risperidone. TaqI A and -141C Ins/Del polymorphisms were
      determined, and the plasma concentrations of risperidone and 9-hydroxyrisperidone
      were measured. The TaqI A polymorphism had no effect on therapeutic efficacy, but
      the -141C Ins/Del polymorphism was associated with an improvement in positive
      symptoms. In addition, the plasma concentration of the active moiety (risperidone
      plus 9-hydroxyrisperidone) correlated with the improvement in the total Brief
      Psychiatric Rating Scale score as well as with positive symptoms. Although there
      were no associations between DRD2 polymorphisms and psychic adverse effects, the
      plasma drug concentration was associated with psychic adverse effects. These
      findings suggest that DRD2 polymorphisms are associated with the therapeutic
      effects of risperidone as they relate to positive symptoms and that plasma drug
      concentrations are associated with overall symptoms as well as excitement and
      cognitive symptoms. Both the genotyping of DRD2 and the monitoring of plasma drug
      concentrations may be useful for improving clinically dominant symptoms. Further
      work involving replication in a larger sample is required to support our
      findings.

PMID- 21869690
TI  - Efficacy of antidepressant medications in children and adolescents with obsessive
      compulsive disorder: a systematic appraisal.
AB  - The aim of this article was to analyze systematically literature information
      published in English (between 1966 and January 2011) on the efficacy of
      antidepressants in pediatric obsessive-compulsive disorder. Data were identified
      through different databases by using variously combined patterns of search terms.
      Searches provided 85 articles, excluding duplicates, but only articles reporting
      primary data on use of antidepressants in this specific disorder were reviewed.
      Fifty-nine articles were excluded because they did not report primary efficacy
      data or investigated patients with different psychiatric diagnosis. Twenty-five
      electronically recognized articles met the inclusion criteria. Two additional
      studies, available as congress communication, were identified by manually
      checking the references' list of electronically identified articles. Reviewed
      studies show several methodological biases (the lack/limited number of long-term
      trials and head-to-head comparisons and the inclusion of patients who continued
      different forms of psychotherapy), which make it difficult to individuate the
      best pharmacological strategy. Despite these limitations, evidence-based
      information suggests that clomipramine and sertraline, especially for long-term
      treatments, should be considered as first-choice agents for treating obsessive
      compulsive disorder at onset during childhood or adolescence.

PMID- 21869691
TI  - Antipsychotics, antidepressants, anticonvulsants, and placebo on the symptom
      dimensions of borderline personality disorder: a meta-analysis of randomized
      controlled and open-label trials.
AB  - The aim of this study was to quantitatively review randomized controlled trials
      (RCTs) and open-label trials analyzing the efficacy of antidepressants, mood
      stabilizers, and antipsychotics for the treatment of the core symptoms of
      borderline personality disorder (BPD). Using a similar meta-analytic approach,
      the efficacy of placebo on the same core symptoms of BPD was evaluated. The risk
      of discontinuation of each of the medication classes reported in the studies was
      also analyzed to establish the major causes of discontinuation. MEDLINE (1966 to
      June 2010) and EMBASE (1980 to June 2010) databases were systematically searched
      to identify relevant RCTs and open studies. The primary outcome was improvement
      in the specific core symptoms of the disorder: affective dysregulation, impulsive
      behavioral dyscontrol, and cognitive-perceptual symptoms. Evidence from RCTs and
      open studies suggests that drug treatment, especially with mood stabilizers and
      antipsychotics, may be effective for treating affective dysregulation and
      impulsive-behavioral dyscontrol. Antipsychotics were also effective in reducing
      cognitive-perceptual symptoms. Antidepressants failed to show efficacy in
      treating BPD symptom dimensions other than affective dysregulation. Our analyses
      of the placebo arm of RCTs showed a significant improvement of symptomatology in
      these patients also. There were no significant differences in overall dropout
      rates between patients on medications and those on placebo. In conclusion, the
      efficacy of pharmacological treatment on the symptom dimensions of BPD has been
      shown by various independent meta-analyses, with a positive effect of drug
      treatment on the core symptoms of BPD and some documentable differences in terms
      of efficacy between different drug classes in each of the symptom domains.

PMID- 21869692
TI  - Antagonist-elicited cannabis withdrawal in humans.
AB  - Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but
      antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male
      daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Delta9
      tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize
      cannabis dependence while residing on a closed research unit. On the ninth day,
      double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral
      rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis
      withdrawal signs and symptoms were assessed before and for 23.5 hours after
      rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were
      quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant
      (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo).
      Fourteen subjects enrolled; 10 completed before premature termination because of
      withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20
      mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the
      prespecified withdrawal criterion of 150% increase or higher in at least 3 visual
      analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant
      dosing. There were no significant associations between visual analog scale, heart
      rate, or blood pressure changes and peak rimonabant plasma concentration, area
      under-the-rimonabant-concentration-by-time curve (0-8 hours), or peak
      rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios.
      In summary, prespecified criteria for antagonist-elicited cannabis withdrawal
      were not observed at the 20- or 40-mg rimonabant doses. These data do not
      preclude antagonist-elicited withdrawal at higher rimonabant doses.

PMID- 21869693
TI  - A double-blind, placebo-controlled trial of the NMDA glycine site antagonist,
      GW468816, for prevention of relapse to smoking in females.
AB  - Relapse to smoking is common after initial abstinence with pharmacotherapy and
      behavioral support and represents a major clinical challenge. Although mechanisms
      underlying relapse to smoking have not been elucidated, preclinical studies
      suggest that glutamate receptors may be involved. We sought to test a selective
      antagonist of the glycine coagonist site on the glutamate N-methyl-D-aspartate
      receptor, GW468816, for prevention of relapse in recently abstinent smokers. To
      do so, we enrolled 264 healthy female smokers in an open 8-week smoking cessation
      intervention with behavioral therapy and a standard dose of transdermal nicotine
      replacement therapy with taper and additional gum or lozenge as needed for
      nicotine withdrawal symptoms. Ninety-eight participants achieved 7-day point
      prevalence abstinence and were randomized into a 5-week double-blind, placebo
      controlled, relapse-prevention trial of GW468816 (200 mg/d) and then followed for
      60 days after randomization. There was no effect of treatment on abstinence rates
      at the end of treatment (chi2 [1, n = 96] = 0.168, P = 0.838), on the rates of
      relapse (chi2 [1, n = 98] = 0.031, P = 1.000) or lapse (chi2 [1, n = 62] = 0.802,
      P = 0.423), or on time to relapse (chi2 [1, n = 98) = 0.001, P = 0.972). No
      significant relationships were detected between plasma GW468816 concentrations
      and abstinence, time to relapse, or self-reported craving. In conclusion, despite
      promising preclinical data that support the use of a selective NMDA glycine site
      antagonist for prevention of relapse to smoking, we observed no effect of
      GW468816 on relapse or lapse rates, time to relapse, or craving compared to
      placebo.

PMID- 21869694
TI  - Importance of gabapentin dose in treatment of opioid withdrawal.
AB  - AIM: The aim of the study was to evaluate the efficacy of gabapentin (1600 mg/d)
      as an adjunctive to methadone-assisted detoxification in the treatment of opioid
      withdrawal symptoms. DESIGN: This was a 3-week open-label study (as second phase)
      following a double-blind, placebo-controlled study with 900 mg/d of gabapentin
      (as first phase of this study). SETTING: The study was conducted at a specialized
      outpatient clinic for the treatment of patients with addictive disorders.
      PARTICIPANTS: The study subjects were composed of 27 patients addicted to opiate
      who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revision criteria for opioid dependency, randomly selected among
      outpatients referred to our clinic. INTERVENTION: Subjects received adjunctive
      treatment with gabapentin (1600 mg/d) in addition to methadone-assisted
      detoxification for 3 weeks. MEASUREMENTS: Subjective Opiate Withdrawal Scale
      (SOWS) with a total score of 0 to 64 was administered at 6 time points during the
      study. FINDINGS: The total SOWS score was significantly decreased after the
      intervention. Compared to our previous trial, an almost significant difference
      was observed in total SOWS scores between groups treated with gabapentin 1600 and
      900 mg/d at the end of the intervention period (P = 0.06). Gabapentin with a dose
      of 1600 mg/d was significantly superior to a dose of 900 mg/d in decreasing
      severity of coldness, diarrhea, dysphoria, yawing, and muscle tension.
      CONCLUSIONS: Add-on gabapentin with a dose of 1600 mg/d is effective in reducing
      some of the withdrawal symptoms in patients addicted to opiate undergoing
      methadone-assisted detoxification.

PMID- 21869695
TI  - The effects of donepezil on computer-simulated driving ability among healthy
      older adults: a pilot study.
AB  - The purpose of the present pilot study was to examine the effect of donepezil on
      simulated driving among healthy older adults. Twenty participants with a mean age
      of 72 years were randomized to take 5 mg of donepezil or placebo for 2 weeks. All
      participants were assessed at baseline and 2 weeks later on measures of
      attention, global cognition, and simulated driving on the York driving simulator.
      Driving measures included speed deviation, deviation of road position, reaction
      time to wind gusts, and collisions. Groups were compared using analysis of
      covariance, controlling for baseline values. There were no differences between
      the groups on attentional measures, number of collisions, or composite simulator
      measures. The placebo group fared approximately 0.5 second better in reaction
      time to wind gusts and showed a nonsignificant tendency toward less deviation of
      road position, compared with the donepezil group. This analysis does not support
      the use of donepezil to extend the period of safe driving among older adults, but
      further study is needed regarding its role among patients with cognitive
      disorders.

PMID- 21869696
TI  - Treatment of major depressive disorder and dysthymic disorder with
      antidepressants in patients with comorbid opiate use disorders enrolled in
      methadone maintenance therapy: a meta-analysis.
AB  - Depression and opiate-use disorders (abuse, dependence) often co-occur, each
      condition complicating the course and outcome of the other. It has been
      recommended that clinicians prescribe antidepressant therapy for mood symptoms in
      patients with active substance-use disorders, but whether antidepressants are
      effective in this specific population is not entirely clear. Therefore, the aim
      of this study was to examine the efficacy of antidepressants in patients with
      unipolar major depressive disorder (MDD) and/or dysthymic disorder (DD) with
      comorbid opiate-use disorders currently in methadone maintenance treatment (MMT).
      Medline/PubMed publication databases were searched for randomized, double-blind,
      placebo-controlled trials of antidepressants used as monotherapy for the
      treatment of MDD/DD in patients with comorbid opiate-use disorders currently in
      MMT. The search was limited to articles published between January 1, 1980, and
      June 30, 2010 (inclusive). Four manuscripts were found eligible for inclusion in
      our analysis (n = 317 patients). We found no statistically significant difference
      in response rates between antidepressant and placebo therapy in trials of MDD/DD
      patients with comorbid opiate-use disorders currently in MMT (risk ratio for
      response, 1.182; 95% CI: 0.822-1.700; P = 0.366). These results show no
      difference in the depressive outcome of patients with comorbid opiate-use
      disorders on MMT whether they are on medication or placebo. Future studies
      examining the effectiveness of antidepressants while controlling for several
      variables such as psychosocial treatment and assessing the specific classes of
      antidepressants are needed.

PMID- 21869697
TI  - Faster onset of antidepressant effects of citalopram compared with sertraline in
      drug-naive first-episode major depressive disorder in a Chinese population: a 6
      week double-blind, randomized comparative study.
AB  - Several previous studies, including a meta-analysis, reported no significant
      differences between various selective serotonin reuptake inhibitors (SSRIs) in
      the treatment of major depressive disorder. However, because of the different
      chemical structure of SSRIs and the difference in the frequency of serotonin
      transporter polymorphisms between ethnic groups, a head-to-head comparative study
      between SSRIs in different populations may be enlightening. We compared the
      efficacy and adverse effect profiles of citalopram and sertraline in a double
      blinded randomized clinical trial in a Chinese population of drug-naive patients
      with first-episode major depressive disorder. Fifty-one patients were randomly
      assigned to citalopram or sertraline treatment. The Montgomery-Asberg Depression
      Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse
      effects were analyzed in an intent-to-treat population. Efficacy was analyzed
      using a last-observation-carried-forward method for early terminators. There were
      no significant differences in demographic characteristics at baseline. No
      significant differences were found in MADRS scores between citalopram and
      sertraline at baseline (36.6 +/- 5.5 vs 38.2 +/- 4.9; P = 0.322) or at the end of
      treatment (week 6; 10.8 +/- 10.0 vs 16.7 +/- 11.3; P = 0.082). However, MADRS
      scores in the citalopram group were significantly lower at week 1 (25.2 +/- 8.5
      vs 30.4 +/- 6.1; P = 0.029) and week 3 (15.9 +/- 10.0 vs 22.1 +/- 8.7; P =
      0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and
      28.6% of patients in the citalopram and sertraline groups, respectively. In
      conclusion, citalopram and sertraline were both efficacious and well tolerated.
      However, citalopram exhibited a significantly faster onset than sertraline during
      the early weeks of treatment and tended to have a better efficacy in overall
      treatment, although the statistic was not significant.

PMID- 21869698
TI  - Symptomatic and functional improvement in employed depressed patients: a double
      blind clinical trial of desvenlafaxine versus placebo.
AB  - OBJECTIVE: This is the first study to assess the efficacy of desvenlafaxine
      (administered as desvenlafaxine succinate) for improving depressive symptoms and
      functioning exclusively in employed patients with major depressive disorder
      (MDD). METHODS: Gainfully employed (>=20 h/wk) male and female outpatients with
      MDD were randomly assigned (2:1 ratio) to 12 weeks of double-blind treatment with
      desvenlafaxine 50 mg/d or placebo. Analysis of covariance was used to compare
      differences in week 12 adjusted mean changes from baseline on the 17-item
      Hamilton Depression Rating Scale (HAM-D17) (primary outcome) and Sheehan
      Disability Scale (SDS) (key secondary outcome) in the intent-to-treat (ITT)
      population. A predefined, modified ITT population (ie, those in the ITT
      population with baseline HAM-D17 >=20) was also analyzed. Tolerability was
      assessed by recording adverse events and change on the Arizona Sexual Experience
      Scale. RESULTS: Baseline HAM-D17 scores for desvenlafaxine (n = 285) and placebo
      (n = 142) were 22.0 and 21.8, whereas baseline SDS scores were 19.8 and 20.4.
      Adjusted mean differences between desvenlafaxine and placebo were 2.1 (95%
      confidence interval [CI], 0.78-3.46; P = 0.002) on the HAM-D17 and 1.3 (95% CI, 
      0.09 to 2.76; P = 0.067) on the SDS. For the modified ITT sample, desvenlafaxine
      (n = 208) and placebo (n = 102), baseline HAM-D17 scores were 23.8 and 23.9; the
      SDS baseline scores were 20.1 and 20.8. Mean differences were 2.6 (95% CI, 0.93
      4.22; P = 0.002) on the HAM-D17 and 2.1 (95% CI, 0.36-3.76; P = 0.017) on the
      SDS. Adverse events and Arizona Sexual Experience Scale scores were comparable
      between groups. CONCLUSIONS: Desvenlafaxine 50 mg/d was efficacious for treating
      MDD in gainfully employed adults. Between-group differences on the SDS narrowly
      missed statistical significance in the ITT population alone, but the totality of
      data suggests functional improvements with active treatment.

PMID- 21869699
TI  - Adjunctive low-dose aripiprazole with standard-dose sertraline in treating fresh
      major depressive disorder: a randomized, double-blind, controlled study.
AB  - OBJECTIVES: Second-generation (atypical) antipsychotics have been accepted as an
      adjunctive medication in patients with treatment-resistant depression. This
      clinical trial evaluated the efficacy and safety of low-dose aripiprazole
      combined with regular-dose sertraline for acute major depressive episode in non
      treatment-resistant depression outpatients. METHODS: The study patients were 18-
      to 65-year-old outpatients fulfilling the criteria of major depressive disorder
      in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The
      patients were randomly assigned to 2 groups: one with sertraline 50 mg/d plus
      aripiprazole 2.5 mg/d and the other with sertraline 50 mg/d plus placebo. After
      baseline assessment, the subjects were followed up at weeks 1, 2, 4, 6, and 10.
      The primary efficacy was the score change of the 17-item Hamilton Rating Scale
      for Depression (HAM-D17), and secondary efficacies were the score of Short Form
      36 Health Survey, Clinical Global Impressions-Severity, and Clinical Global
      Impressions-Improvement. This study also monitored patients for movement disorder
      using Simpson-Angus Scale and Barnes Akathisia Rating Scale. RESULTS: Twenty-one
      patients were assigned to the aripiprazole group and 20 to the placebo group.
      Because of high dropout rate, only data of the first 4 weeks were analyzed. The
      aripiprazole group exhibited significantly better efficacy than the placebo group
      in mean total score changes of HAM-D17 from the baseline to weeks 1, 2, and 4.
      The item "work and social activities" of HAM-D17 showed significant improvement
      at week 2, and the item "somatic symptoms (GI)" showed significant improvement at
      week 1. The aripiprazole group exhibited significant improvement in "social role
      function" section of Short Form 36 Health Survey at week 4. The mean total score
      of Clinical Global Impressions-Severity showed marginally significant improvement
      in the aripiprazole group. In Clinical Global Impressions-Improvement, patients
      in the aripiprazole group had scores of less than 2 (much improved) at weeks 2
      and 4, and the scores of the placebo group were greater than 2.4 (indicating a
      minimal improvement). No patients had akathisia during the trial period.
      CONCLUSIONS: The primitive data showed that adjunctive low-dose aripiprazole
      could augment the efficacy of regular-dose sertraline in fresh major depressive
      disorder. A large-scale study is needed to confirm this finding.

PMID- 21869700
TI  - DRD2 Taq1A polymorphism modulates prolactin secretion induced by atypical
      antipsychotics in healthy volunteers.
AB  - Hyperprolactinemia mediated by antagonism of dopaminergic neurotransmission in
      the pituitary gland is a common adverse effect of antipsychotics. Recent studies
      have suggested that polymorphisms of dopamine receptors can affect the
      therapeutic response to antipsychotics. Thus, our aim was to evaluate whether 2
      such polymorphisms (DRD2 Taq1A and DRD3 Ser9Gly) modulate prolactin release in
      healthy volunteers (n = 119) receiving a single dose of quetiapine (25 mg, n =
      26), olanzapine (5 mg, n = 57), or risperidone (1 mg, n = 36). The increases in
      maximum concentration and in area under the curve were calculated from plasma
      prolactin levels after subtraction of pretreatment levels. Multiple regression
      analyses revealed that prolactin increases in maximum concentration and in area
      under the curve depended on drug (quetiapine < olanzapine < risperidone; P <
      0.001), sex (women > men; P < 0.001), and Taq1A polymorphism (A1+ > A2/A2; P <
      0.05). Analysis of the individual drugs revealed that prolactin secretion was
      modulated by sex and Taq1A polymorphism in olanzapine and risperidone (P < 0.05);
      however, these factors were not linked to prolactin secretion in quetiapine.

PMID- 21869701
TI  - Central nervous system drug development, basic, and clinical research: thinking
      outside the box.

PMID- 21869702
TI  - Extreme hypereosinophilia, Churg-Strauss syndrome and mononeuritis multiplex.

PMID- 21869703
TI  - Chondrocalcinosis and hypomagnesemia in a 26-year-old woman.

PMID- 21869704
TI  - Amyopathic dermatomyositis presenting as skin necrosis.

PMID- 21869705
TI  - Relapsing polychondritis with encephalitis.

PMID- 21869706
TI  - Tumor necrosis factor receptor-associated periodic fever syndrome in a 58-year
      old man: caution not to discount TRAPS as a diagnosis in older patients.
AB  - Tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS) is a
      rare systemic autoinflammatory disorder characterized by recurrent episodes of
      fever and localized inflammation of different organs. The disease is dominantly
      inherited, with an onset usually in early childhood. We describe a case of a 58
      year-old patient with TRAPS caused by the low-penetrance R92Q mutation in
      TNFRSF1A gene. The patient responded well to anti-tumor necrosis factor alpha
      therapy. Although periodic fever syndromes, including TRAPS, mainly begin in
      early childhood, it is important to consider periodic fever syndrome also in
      patient presenting at an age older than the average reported case for TRAPS.

PMID- 21869707
TI  - Esophageal adenocarcinoma and hypertrophic osteoarthropathy with improvement
      following resection of esophageal cancer.
AB  - Esophageal cancer usually presents late and carries a grave prognosis. Early
      diagnosis dramatically improves outcomes, and hence recognition of the varied
      presenting features, including hypertrophic osteoarthropathy (HOA), may be
      important. Hypertrophic osteoarthropathy is a rare manifestation of esophageal
      adenocarcinoma and indeed may herald the presence of this neoplasm, as it did in
      the case we present. A 59-year-old man presented with signs and symptoms
      suggestive of inflammatory wrist, ankle, and knee arthritis, and imaging revealed
      changes of HOA. He reported dysphagia mainly to solids, and endoscopic biopsy
      showed adenocarcinoma. Cancer resection treatment led to clinical resolution of
      his musculoskeletal symptoms. This case highlights the importance of recognition
      of HOA as a feature of this increasingly common cancer.

PMID- 21869708
TI  - Scleroderma renal crisis-like acute renal failure associated with
      mucopolysaccharide accumulation in renal vessels in a patient with
      scleromyxedema.
AB  - Scleromyxedema is a systemic disease characterized by lichenoid papules, nodules,
      and plaques on the skin and often diffuse skin induration resembling the
      cutaneous involvement of systemic sclerosis. The systemic involvement affects the
      musculoskeletal, pulmonary, cardiovascular, gastrointestinal, and central nervous
      systems, and the disorder is commonly associated with a paraproteinemia.
      Involvement of the kidney is rare and not considered a feature of the disease.
      Here, we describe an unusual case of scleromyxedema complicated by the
      development of scleroderma renal crisis-like acute renal failure with a marked
      intimal deposition of mucin, mucopolysaccharides, and hyaluronic acid in the
      intrarenal vessels.

PMID- 21869709
TI  - Refractory adult-onset still disease successfully treated with abatacept.
AB  - Adult-onset Still disease (AOSD) is an inflammatory condition of unknown etiology
      that responds to glucocorticosteroids and disease-modifying antirheumatic drugs,
      particularly methotrexate. However, disease refractory to conventional treatment
      has led to the reported use of biologic therapy including tumor necrosis factor
      alpha inhibitors (infliximab, etanercept, and adalimumab), anakinra, rituximab,
      and tocilizumab. We report the successful use of abatacept in the treatment of a
      patient with AOSD manifested by polyarthritis, rash, fevers, elevated liver
      function tests, and ferritin levels refractory to treatment with methotrexate and
      hydroxychloroquine. Remission has been maintained for 35 months with the addition
      of abatacept administered once monthly. There is evidence that T-cell activity
      plays an important role in the autoimmune activity of AOSD, and modulation of
      CD28 costimulation of T cells by abatacept has specific immunosuppressive actions
      that make it an appealing alternative therapeutic option for refractory AOSD.

PMID- 21869710
TI  - Capillaroscopic pattern at the toes of systemic sclerosis patients: does it
      "tell" more than those of fingers?
AB  - PURPOSE: The aim of the study was to compare nail fold capillaroscopic findings
      of the fingers with those of the toes in patients with systemic sclerosis (SSc).
      METHODS: Thirty-six patients with SSc were included in the study: 30 patients had
      limited SSc, 5 patients had diffuse SSc, and 1 patient had an overlap syndrome.
      Of these 36 patients, 30 were women and 6 were men (mean [SD] age, 56 [14]
      years). The severity of the Raynaud phenomenon (RP), the presence of digital
      ulcers, and skin scores at the fingers and feet were assessed. Nail fold
      capillaroscopy was performed with a videocapillaroscope (Videocap 3.0; DS
      Medica). RESULTS: All 36 patients (100%) reported about symptoms of RP in the
      hands and 34 (94.4%) reported episodes of RP in the feet; the difference is not
      significant (P > 0.05). In most patients with RP symptoms of both hands and feet,
      the symptoms were more severe at the hands (82%, 28/34). Digital ulcers of the
      fingers were found in 36% (13/36) of the case and those of the toes were found in
      8.3% (3/36) of the cases. Nail fold capillaroscopy of the hands showed the
      classic "scleroderma"-type capillaroscopic pattern in 97.2% (35/36) of the
      patients. In the toes, a scleroderma-type capillaroscopic pattern was found only
      in 66.7% (24/36) of patients (P < 0.05). With respect to distinct differences, in
      the toes, the dilated capillaries were found in 72.2% (26/36) of the cases, giant
      capillaries in 30.6% (11/36) of the cases, hemorrhages in 8.3% (3/36) of the
      cases, avascular areas in 41.7% (15/36) of the cases, and neoangiogenesis in
      22.1% (8/36) of the cases. This difference in frequency of the findings regarding
      the toes and the fingers of patients with SSc was statistically significant for
      all parameters. CONCLUSIONS: Capillaroscopy of the toes of SSc also shows
      patterns characteristic of SSc. However, these patterns differ from the
      respective patterns of the fingers, which is probably related to less-severe RP
      and lower skin score at the feet.

PMID- 21869711
TI  - Magnetic resonance angiography in extracranial giant cell arteritis.
AB  - BACKGROUND: Noninvasive diagnosis of giant cell arteritis (GCA) remains
      challenging, particularly with regard to evaluation of extracranial arterial
      disease. OBJECTIVES: The objective of the study was to retrospectively review
      extracranial involvement in patients with GCA and/or polymyalgia rheumatica
      (PMR), evaluated with magnetic resonance imaging (MRI), especially 3-dimensional
      contrast-enhanced magnetic resonance angiography images of the aortic arch and
      its branches. METHODS: Clinical information, biopsy status, and MRI examinations
      of 28 patients with GCA/PMR were reviewed. Patient images were mixed randomly
      with 20 normal control images and were independently reviewed by 2 radiologists.
      Interobserver agreement for detection of arterial stenosis was determined by the
      k coefficient. RESULTS: Both readers described vascular alterations in keeping
      with extracranial GCA in 19 of 28 patients (67%) with good interobserver
      agreement (k = 0.73) and with even higher agreement on diagnosing nonocclusive
      versus occlusive disease (k = 1.00). The most common lesions were bilateral
      axillary stenosis or obstructions, observed by both readers in 8 patients (28%).
      Among the 19 patients with magnetic resonance angiography lesions in the
      subclavian/axillary arteries, 12 (75%) had biopsy-proven GCA, but only 5 (41%) of
      these patients had clinical features of large artery disease. CONCLUSIONS: In our
      series review, MRI could provide accurate information on involvement of the
      aortic arch and its branches in extracranial GCA, depicting different degrees of
      stenosis. Our analysis also illustrates that occult large artery vasculitis
      should be considered in patients without biopsy-proven GCA, patients with classic
      GCA but without clinical signs of large artery disease, and in patients initially
      diagnosed as having PMR.

PMID- 21869712
TI  - The effect of intra-articular triamcinolone preparations on blood glucose levels
      in diabetic patients: a controlled study.
AB  - OBJECTIVES: The objective of the study was to evaluate the effect of intra
      articular (IA) triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TA)
      on blood glucose levels in patients with controlled diabetes with symptomatic
      osteoarthritis of the knee (OAK). METHODS: Patients with controlled diabetes with
      symptomatic OAK who failed nonsteroidal anti-inflammatory medication and physical
      therapy and use modern versions of self-monitoring blood glucose devices were
      offered an IA injection of either 20 mg of TAH or 40 mg of TA. If agreed,
      patients were asked to document blood glucose levels before and 2 hr after meals
      for 1 week before and daily for 5 days then every other day for 1 week following
      the injection. The type of IA preparation was given on an alternating pattern. A
      sex- and aged-matched group of patients with controlled diabetes with symptomatic
      OAK of the knee was offered an IA hyaluronic acid (HA) injection. Significantly
      increased blood glucose level following the IA injection was defined as higher by
      at least 2 SDs than the mean comparable level before the injection. RESULTS:
      Thirty patients completed the study: 12 patients in the TAH, 12 patients in the
      TA group, and 6 in the HA group. All the patients who received triamcinolone
      preparations had significantly increased blood glucose levels with median initial
      levels of 227.5 and 201 mg% seen at a median of 8.5 and 13 hr following the IA
      injection and median peak levels of 288 and 239.5 mg% seen after a median of 24.5
      and 32.5 hr following the IA injection of TA and TAH, respectively. Levels
      returned to normal after ~2.5 to ~4 days. There was no significant increase in
      the HA group except in 1 measurement only with marginal level in 2 patients.
      CONCLUSIONS: Intra-articular injection of either TAH or TA is associated with
      significantly increased blood glucose levels in patients with controlled diabetes
      with OAK. This increase is quite solely due to the injected steroids.

PMID- 21869713
TI  - Relevance of physical fitness levels and exercise-related beliefs for self
      reported and experimental pain in fibromyalgia: an explorative study.
AB  - BACKGROUND: It has been suggested that low physical fitness is a contributor to
      pain in fibromyalgia and that exercise-related beliefs play a role in the
      persistence of this association. Yet the association between physical fitness and
      pain is hardly explored in detail. OBJECTIVES: The aim of this exploratory study
      in patients with fibromyalgia was to investigate the association of physical
      fitness levels with self-reported and experimental pain as well as with pain
      catastrophizing and activity-avoidance beliefs. METHODS: Physical fitness of 18
      patients with fibromyalgia was examined using maximal ergocycling and the 6
      minute walking test (6MWT). Pain intensity was assessed using self-report scales
      and quantitative sensory testing. RESULTS: A reduced walking distance on the 6MWT
      was correlated with more severe self-reported pain on the Fibromyalgia Impact
      Questionnaire (r = -0.52, P < 0.05). Recovery of heart rate after ergocycling was
      correlated with cold pain thresholds (r = 0.70, P < 0.01), pressure pain
      thresholds (r = -0.70, P < 0.01), and heat wind-up (r = 0.66, P < 0.05). Activity
      avoidance beliefs correlated with a lower peak VO2 on the cycle test (r = -0.52,
      P < 0.05), a shorter distance on the 6MWT (r = -0.56, P < 0.05), and more severe
      self-reported pain (r = 0.61, P < 0.05), reflecting that patients with activity
      avoidance beliefs were less physically fit and experienced more severe pain.
      CONCLUSIONS: The results demonstrate some associations between physical fitness
      and pain in fibromyalgia and point to the importance of activity avoidance.
      Although the causal directionality of the associations needs substantiation in
      clinical research, the findings support the notion that low fitness and activity
      avoidance beliefs should be targeted while treating pain in fibromyalgia.

PMID- 21869714
TI  - Clinical and testing protocols for the analysis of epidermal growth factor
      receptor mutations in East Asian patients with non-small cell lung cancer: a
      combined clinical-molecular pathological approach.
AB  - BACKGROUND: Several randomized phase III studies in advanced stage non-small cell
      lung cancer (NSCLC) confirmed the superior response rate and progression-free
      survival of using epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor as first-line therapy compared with chemotherapy in patients with
      activating EGFR mutations. Despite the need for EGFR mutation tests to guide
      first-line therapy in East Asian NSCLC, there are no current standard clinical
      and testing protocols. METHODS: A consensus meeting was held involving expert
      oncologists, pulmonologists, and pathologists to discuss the current status and
      variations in EGFR mutation testing of NSCLC across Asia and to recommend a
      standard clinical and laboratory testing approach for future use. RESULTS:
      Currently, EGFR mutation tests are only routinely performed in some East Asian
      countries and medical centers. The consensus recommendation was to perform the
      test in all newly diagnosed patients with advanced stage nonsquamous lung cancer
      and some squamous patients with clinical features associated with higher
      prevalence of EGFR mutations. To increase the sensitivity and specificity of the
      EGFR mutation tests, tissue acquisition and pretest sample evaluation are
      important steps in addition to standardization of the EGFR mutation test
      methodology. CONCLUSION: A standardized EGFR mutation testing protocol is an
      essential step toward realization of personalized medicine in East Asian NSCLC
      treatment.

PMID- 21869715
TI  - Outcome after pulmonary metastasectomy: analysis of 5 years consecutive surgical
      resections 2002-2006.
AB  - INTRODUCTION: In this study, we analyze the results of management of pulmonary
      metastases in 5 years consecutive operations at our institution. We aim to define
      the patients who are most likely to benefit from surgery by investigating long
      term survival and prognostic factors associated with prolonged survival. METHODS:
      The data on all consecutive patients between 2002 and 2006 were reviewed
      retrospectively. One hundred seventy-eight patients underwent 256 surgical
      resections for suspected pulmonary metastases from different primary
      malignancies. Prognostic factors analyzed included age, sex, surgical approach,
      surgical resection, number of metastases, distribution of metastases, disease
      free interval, presence of synchronous metastases, recurrence of disease, prior
      liver resection (colorectal cancer), and tumor histology (sarcomas). RESULTS:
      Complete resection was achieved in 248 cases (96.8%). The mean follow-up was 61.6
      months. Five-year survival with respect to primary malignancy was colorectal
      carcinoma (50.3%), sarcoma (21.7%), malignant melanoma (25.0%), renal cell
      carcinoma (51.4%), and miscellaneous malignancies (50.0%). Of the prognostic
      factors analyzed by univariate analysis, none was found to be significant in all
      the different groups of cancers. CONCLUSIONS: Pulmonary metastasectomy is a safe
      and effective treatment that may be associated with prolonged survival in highly
      selected patients. Low morbidity and mortality rates in contrast with the lack of
      any other effective treatment justify the aggressive approach of surgery.
      Thoracoscopic resection is a valid option in selected patients. In case of
      recurrence of pulmonary disease and if the patient fulfils the initial criteria
      for pulmonary metastasectomy, repeat surgery should be performed. Solid
      prognostic factors still need to be established.

PMID- 21869716
TI  - Histological subtypes of lung adenocarcinoma have differential 18F
      fluorodeoxyglucose uptakes on the positron emission tomography/computed
      tomography scan.
AB  - INTRODUCTION: Previous studies have shown that lung squamous cell carcinoma has
      higher 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)
      than adenocarcinoma. We hypothesized that histological subtypes of lung
      adenocarcinoma were also different in 18F-FDG uptake. METHODS: Patients who had
      preoperative PET/computed tomography (CT) scan and had undergone complete
      resection for lung adenocarcinoma between April 2007 and December 2009 were
      enrolled in this study. Because of the limitation of spatial resolution on
      PET/CT, tumors less than 1 cm were excluded for analysis. Two independent
      classification systems were used to categorize histological subtypes of
      adenocarcinoma; one was modified from the current World Health Organization
      classification and the other used the morphological features of the terminal
      respiratory unit (TRU). The maximal standardized uptake value (SUVmax) on PET/CT
      and the glucose transporter type 1 (GLUT-1) expression of the tumors were
      measured and correlated to the histology of lung adenocarcinoma. RESULTS: One
      hundred fifty-two patients with 153 primary lung adenocarcinomas were included.
      There was a significant difference in SUVmax among different histological
      subtypes. Namely, solid predominant adenocarcinomas had significantly higher
      SUVmax than those with other predominant histology (p < 0.001), and TRU-type
      adenocarcinomas had significantly lower SUVmax than non-TRU-type adenocarcinomas
      (p < 0.001). Consistently, GLUT-1 expression was higher in tumors with a solid
      growth pattern than those without (p < 0.001) and in tumors with non-TRU type
      than TRU type (p < 0.001). CONCLUSIONS: The histological subtypes of lung
      adenocarcinomas differ in GLUT-1 expression and 18F-FDG uptake on the PET/CT
      scan, suggesting that histological subtyping not only has morphological but also
      biological implications.

PMID- 21869717
TI  - Node-negative non-small cell lung cancer: pathological staging and survival in
      1765 consecutive cases.
AB  - INTRODUCTION: This study aimed to evaluate prognostic factors in patients with
      node-negative non-small cell lung cancer and to assess revised International
      Association for the Study of Lung Cancer staging recommendations for this group.
      METHODS: A retrospective analysis of 1765 consecutive pathologically node
      negative patients treated by surgical resection between 1984 and 2007 was
      performed. Survival analysis was conducted using the Kaplan-Meier method. The
      independence of prognostic factors was analyzed using multivariate Cox
      proportional hazards modeling. RESULTS: The median age of patients was 68 years,
      and the average length of follow-up was 6.3 years. Perioperative mortality was
      1.7%. The median survival was 6.5 years, with a 56% of the cohort surviving 5
      years. Factors associated with poorer prognosis were male gender (hazard ratio
      [HR]: 1.30, p = <0.001), age (HR: 1.04 per year of increase, p < 0.001), limited
      resection (HR: 1.30, p = 0.002) tumor size (HR: 1.10 per 10 mm increase, p <
      0.001), large cell histopathological cell type (HR: 1.35, p < 0.001), and
      positive resection margins (HR: 1.58, p = 0.002). T stage was a superior
      predictor of survival than tumor size (p < 0.001). There was no difference in
      survival by T-stage descriptor within stage T2 or T3. CONCLUSIONS: In surgically
      treated, node-negative non-small cell lung cancer, revised International
      Association for the Study of Lung Cancer staging criteria stratify survival well.
      Age, gender, and extent of resection are also important predictors of survival.
      Current T-stage descriptor groupings are appropriate.

PMID- 21869718
TI  - Comparison of the diagnostic utility of electromyography, ultrasonography,
      computed tomography, and magnetic resonance imaging in idiopathic carpal tunnel
      syndrome determined by clinical findings.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common nerve entrapment
      syndrome. It is sometimes difficult to diagnose, and a late diagnosis may result
      in permanent nerve damage. Electromyography (EMG), ultrasonography (US), magnetic
      resonance imaging (MRI), and computed tomography (CT) may be performed for the
      diagnosis. The diagnostic accuracy of these tests is well documented, but most of
      these studies accept EMG as the gold standard. OBJECTIVE: To evaluate the
      diagnostic accuracy of EMG, MRI, CT, and US for the diagnosis of carpal tunnel
      syndrome with the use of clinical findings as the gold standard. METHODS:
      Patients suspected to have CTS on presentation to the outpatient clinic were
      evaluated. The tests were performed after a detailed physical examination. Both
      wrists of the 69 patients in the study were investigated. RESULTS: : The
      diagnostic accuracies of all the tests were found to be sufficient. Although EMG
      seemed to have the highest sensitivity and specificity, there was no
      statistically significant difference between the tests. CONCLUSION: EMG or US
      could be used as the first-step test in most cases. If they are both available,
      EMG should be the first choice. They may be performed together when diagnosis is
      challenging. CT may especially be preferred for bone-related pathological
      conditions, whereas MRI may be preferred for soft tissue-related pathological
      conditions. Even though imaging studies have been proven to be powerful
      diagnostic tools for CTS, no conclusive information currently exists to support
      replacing EMG with imaging studies.

PMID- 21869719
TI  - Application of a new fenestrated clip (Yasargil T-bar clip) for the treatment of
      fusiform M1 aneurysm: case illustration and technical report.
AB  - BACKGROUND AND IMPORTANCE: Fusiform intracranial aneurysms (FIAs) are challenging
      to treat by surgical and endovascular means because of their complex morphology
      and configurations. Various surgical techniques, including clip reconstruction,
      wrapping with or without clip enforcement, and trapping with or without bypass,
      have been described extensively. The objective of this study is to describe the
      application of a new fenestrated clip (Yasargil T-bar clip) for the treatment of
      FIAs. CLINICAL PRESENTATION: An FIA on the M1 segment of the middle cerebral
      artery was diagnosed incidentally in a 23-year-old man. The aneurysm was
      visualized after wide dissection of the sylvian fissure. The M1 segment of the
      middle cerebral artery, its branches, and its lenticulostriate arteries were
      identified and dissected. A single fenestrated T-bar clip was applied to
      reconstruct this long FIA after one of the lenticulostriate arteries was
      dissected free of the aneurysm. Postoperative angiography confirmed
      reconstruction of the M1 segment and obliteration of the aneurysm. CONCLUSION:
      Clip reconstruction of an FIA with a fenestrated Yasargil T-bar clip is a new
      application option that effectively reconstructs the parent artery. Application
      of this type of a clip might be advantageous over conventional fenestrated or
      nonfenestrated clip applications, especially in tight surgical fields, because a
      single clip might be sufficient to reconstruct the long segment of the artery.

PMID- 21869720
TI  - The use of intraoperative electrophysiology for the placement of spinal cord
      stimulator paddle leads under general anesthesia.
AB  - BACKGROUND: Placement of spinal cord stimulating paddle leads has traditionally
      been performed under local anesthesia with intravenous sedation to allow
      intraoperative confirmation of appropriate placement. It may be difficult to
      maintain appropriate sedation in certain patients because of medical
      comorbidities. Furthermore, patients undergoing lead revision frequently have
      extensive epidural scarring, requiring multilevel laminectomies to place the
      electrode appropriately. OBJECTIVE: To report our technique of neurophysiologic
      monitoring that allows these procedures to be performed under general anesthesia.
      METHODS: Data from 78 patients who underwent electromyography during laminectomy
      for paddle lead placement were retrospectively reviewed. Seventy patients
      presented for first-time permanent system placement after a successful trial, and
      8 were referred for revision or replacement of previously functioning systems.
      Surgeries were performed under general anesthesia with fluoroscopic guidance.
      Electromyography was used to help define the physiological midline of the spinal
      cord and to guide appropriate lead placement. Somatosensory evoked potentials
      were used as an adjunct to minimize the possibility of neural injury. RESULTS:
      Immediately postoperatively, 75 of 78 patients reported that the paresthesia
      coverage was as good as (or better than) that of the spinal cord stimulation
      trial. At the long-term follow-up, 1 system was removed for infection, and 6
      systems were explanted for lack of efficacy. A total of 64 of the 78 implanted
      patients reported continued pain relief with stimulator use. Revision surgery was
      performed in 9 patients. CONCLUSION: The use of intraoperative electrophysiology
      for the placement of spinal cord stimulation paddle leads under general
      anesthesia is a safe and efficacious alternative to awake surgery.

PMID- 21869721
TI  - Limbic and motor function comparison of deep brain stimulation of the zona
      incerta and subthalamic nucleus.
AB  - BACKGROUND: Psychiatric and neuropsychological side effects of subthalamic
      nucleus (STN) stimulation have been increasingly recognized. Most programming
      regimens focus on contacts 0 and 1, whereas contact 3, which often is located
      near or in the zona incerta (ZI), is usually not used. The question of whether ZI
      stimulation may limit limbic effects has not been answered. OBJECTIVE: To examine
      the effects of short-term stimulation near or in the ZI (contact 3) compared with
      stimulation of the STN using standard trajectories and targeting as measured by
      limbic and motor functions. METHODS: Motor and limbic functions of 11 patients
      with STN DBS were assessed with the Unified Parkinson Disease Rating Scale-3,
      structured gait video analysis, Visual Analog Scale mood scales, task testing of
      impulsivity, and facial recognition under routine STN programming and under
      stimulation in or near the ZI. Postoperative magnetic resonance imaging confirmed
      the location of contact 3 near or in the ZI. RESULTS: Data analysis with repeated
      measures analysis of variance revealed that motor scores remained stable with
      both stimulation settings, with specific improvements in finger taps (P = .02)
      and rapid alternating movements (P = .03) in ZI stimulation. Stimulation near or
      in the ZI led to a decrease in self- reported anxiety and depression (P = .03 for
      both) and an improvement in fear recognition (P = .02). CONCLUSION: We provide
      preliminary evidence that stimulation in or near the ZI results in maintained
      motor function while improving self-reported depression and anxiety in patients
      with bilateral STN DBS. Stimulation in or near the ZI may provide a useful
      programming setting for patients prone to psychiatric side effects.

PMID- 21869722
TI  - Magnetic resonance imaging-guided focused laser interstitial thermal therapy for
      subinsular metastatic adenocarcinoma:  technical case report.
AB  - BACKGROUND AND IMPORTANCE: To describe the novel use of the AutoLITT System
      (Monteris Medical, Winnipeg, Manitoba, Canada) for focused laser interstitial
      thermal therapy (LITT) with intraoperative magnetic resonance imaging (MRI) and
      stereotactic image guidance for the treatment of metastatic adenocarcinoma in the
      left insula. CLINICAL PRESENTATION: The patient was a 61-year-old right-handed
      man with a history of metastatic adenocarcinoma of the colon. He had previously
      undergone resection of multiple lesions, Gamma Knife radiosurgery, and whole
      brain radiation. Despite treatment of a left insular tumor, serial imaging
      revealed that the lesion continued to enlarge. Given the refractory nature of
      this tumor to radiation and the deep-seated location, the patient elected to
      undergo LITT treatment. The center of the lesion and entry point on the scalp
      were identified with STEALTH (Medtronic, Memphis, Tennessee) image-guided
      navigation. The AXiiiS Stereotactic Miniframe (Monteris Medical) for the LITT
      system was secured onto the skull, and a trajectory was defined to achieve access
      to the centroid of the tumor. After a burr hole was made, a gadolinium template
      probe was inserted into the AXiiiS base. The trajectory was confirmed via an
      intraoperative MRI, and the LITT probe driver was attached to the base and CO2
      cooled, side-firing laser LITT probe. The laser was activated and thermometry
      images were obtained. Two trajectories, posteromedial and anterolateral, produced
      satisfactory tumor ablation. CONCLUSION: LITT with intraoperative MRI and
      stereotactic image guidance is a newly available, minimally invasive, and
      therapeutically viable technique for the treatment of deep seated brain tumors.

PMID- 21869723
TI  - Intracerebral abscess associated with the Camino intracranial pressure monitor:
      case report and review of the literature.
AB  - BACKGROUND AND IMPORTANCE: Intracranial pressure (ICP) monitoring is a mainstay
      in the management of traumatic brain injury. Large investigations have validated
      the safety and efficacy of ICP monitors in comatose patients. Clinically relevant
      infections are extremely rare and cerebral abscess has never been reported with
      the Camino device. We describe an exceptional case of a life-threatening
      intracerebral abscess from an intraparenchymal ICP monitor. CLINICAL
      PRESENTATION: A 35-month-old child required 7 days of ICP monitoring after a fall
      from a 2-story window. His hospital course was complicated by severe airway edema
      treated, in part, with high-dose corticosteroid therapy for a total of 10 days.
      Two weeks later, the patient deteriorated acutely owing to a large intracerebral
      abscess under the previous ICP monitor site. Urgent craniotomy with evacuation of
      the abscess was performed on 2 separate occasions. Cultures grew methicillin
      sensitive Staphylococcus aureus, which was treated with long-term antibiotics. At
      the 3-month follow-up, the patient was meeting age-appropriate milestones without
      focal deficits. CONCLUSION: To the best of our knowledge, this is the first
      report describing an intracerebral abscess as a complication from an
      intraparenchymal pressure monitor. Corticosteroid therapy may have constituted an
      independent risk factor for the ICP monitor--associated infection, as well as
      reinsertion of the ICP monitoring device at the same site. That this is the first
      reported parenchymal infectious complication underscores the safety of this
      device with respect to infection. When reinsertion of a parenchymal monitor is
      considered, a new site should be chosen.

PMID- 21869724
TI  - Bending the curve:  preoperative determination of bypass graft length and
      trajectory with curved planar reformatted computed tomography angiography: 
      technical note.
AB  - BACKGROUND AND IMPORTANCE: Cerebral revascularization continues to be an
      important technique for the treatment of cerebrovascular and vaso-occlusive
      diseases, and determination of appropriate graft sources and recipients is
      paramount to the success of the procedure. A tension-free anastomosis requires
      that harvested grafts be of an appropriate length to avoid complications. Volume
      rendered contrast-enhanced computed tomography data sets may be useful in
      determining the desired length and path of the bypass graft and in the evaluation
      of appropriate recipient vessels. Curved planar reformation techniques may allow
      these properties to be determined in a novel, inexpensive, and efficient manner.
      CLINICAL PRESENTATION: A 63-year-old patient with a left hemispheric perfusion
      deficit and without an external carotid artery was in need of high-flow cerebral
      revascularization. A radial artery graft spanning from the vertebral artery to
      the middle cerebral artery was proposed. Preoperative determination of graft
      length necessary and most efficient subcutaneous placement was desired. A
      standard computed tomography angiogram of the head and neck was obtained and
      imported into a computer workstation with curved planar reformatting
      capabilities. CONCLUSION: Curved planar reformation technique can be used for
      preoperative planning of cerebral bypass procedures and is a novel, inexpensive,
      and efficient means of determining the desired length and path of the bypass
      graft and in the evaluation of appropriate recipient vessels.

PMID- 21869725
TI  - Rat multipotent mesenchymal stromal cells lack long-distance tropism to 3
      different rat glioma models.
AB  - BACKGROUND: Viral gene therapy of malignant brain tumors has been restricted by
      the limited vector distribution within the tumors. Multipotent mesenchymal
      stromal cells (MSCs) and other precursor cells have shown tropism for gliomas,
      and these cells are currently being explored as potential vehicles for gene
      delivery in glioma gene therapy. OBJECTIVE: To investigate MSC migration in
      detail after intratumoral and extratumoral implantation through syngeneic and
      orthotopic glioma models. METHODS: Adult rat bone marrow-derived MSCs were
      transduced to express enhanced green fluorescent protein and implanted either
      directly into or at a distance from rat gliomas. RESULTS: We found no evidence of
      long-distance MSC migration through the intact striatum toward syngeneic
      D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus
      callosum to gliomas located in the contralateral hemisphere. After intratumoral
      injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs
      did not proliferate within tumors, suggesting a low risk of malignant
      transformation of in vivo grafted cell vectors. Using a model for surgical glioma
      resection, we found that intratumorally grafted MSCs migrate efficiently within
      glioma remnants after partial surgical resection. CONCLUSION: The findings point
      to limitations for the use of MSCs as vectors in glioma gene therapy, although
      intratumoral MSC implantation provides a dense and tumor-specific vector
      distribution.

PMID- 21869727
TI  - The impact of weekend hospital admission on the timing of intervention and
      outcomes after surgery for spinal metastases.
AB  - BACKGROUND: Many studies have found that patients admitted on the weekend have
      inferior outcomes compared with those admitted on a weekday, which may be due
      partially to decreased availability of procedures. OBJECTIVE: To evaluate the
      impact of weekend admission on the timing of intervention and outcomes after
      surgery for metastatic spine disease. METHODS: Data from the Nationwide Inpatient
      Sample (2005-2008) were retrospectively extracted. Patients were included if they
      had metastatic disease and underwent spine surgery; elective hospital admissions
      were excluded. Multivariate logistic regression analyses were conducted to
      calculate the odds of undergoing early surgery, in-hospital death, and the
      development of a complication for patients admitted on the weekend compared with
      those admitted on a weekday. All analyses were adjusted for differences in age,
      sex, comorbid disease, primary tumor histology, myelopathy, visceral metastases,
      and expected primary payer, as well as hospital volume, bed size, and teaching
      status. RESULTS: We evaluated 2714 admissions. Weekend admission was associated
      with a significantly lower adjusted odds of receiving surgery within 1 day (odds
      ratio, 0.66, 95% confidence interval, 0.54-0.81; P < .001) and within 2 days
      (odds ratio, 0.68; 95% confidence interval, 0.56-0.83; P < .001) of admission.
      The adjusted odds of in-hospital death and developing a postoperative
      complication were not significantly different for those admitted on the weekend.
      CONCLUSION: In this nationwide study examining patients with spinal metastases,
      those admitted on the weekend were significantly less likely to receive early
      intervention. Future studies are needed to delineate the reasons for differences
      in the timing of surgery.

PMID- 21869728
TI  - The value of successive Infecton scans in assessing the presence of chronic bone
      and joint infection and in predicting its evolution after treatment and after a
      prolonged follow-up.
AB  - OBJECTIVE: Our objective was to monitor the evolution of bone and/or joint
      infections with the aid of successive radiolabelled ciprofloxacin (Infecton)
      scans during antimicrobial treatment and to compare the results of an Infecton
      scan at the end of therapy with the respective results of clinical evaluation,
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in predicting
      resolution or recurrence of infection after a long period of posttreatment follow
      up. METHODS: Thirty-three patients with documented bone and/or joint infection
      were subjected to successive Infecton scans on two or three visits. Infecton
      scans were evaluated visually and scored accordingly. Clinical evaluation was
      scored by the referring clinicians. ESR and CRP values were evaluated
      independently. A minimum of 2-year free-of-infection follow-up after
      discontinuation of the antibiotic treatment served as a measure of successful
      antimicrobial therapy and nonrecurrence of infection. Statistics included
      survival analysis (Cox regression). RESULTS: During follow-up, five patients in
      the study presented with recurrence, and three died as a result of an irrelevant
      cause. The remaining patients were followed up for a median of 108 months (range
      97-132 months) without any signs of recurrence of infection. Recurrence of
      infection was 4.2 times more likely to occur in patients with positive Infecton
      scans [hazard ratio (HR): 4.2, confidence intervals 95%: 1.39-12.67, P=0.011].
      Infecton had the highest sensitivity (83.3%), accuracy (69.69%) and negative
      predictive value (94.74%), whereas CRP had the highest specificity (76.92%).
      CONCLUSION: Infecton scintigraphy proved to be more sensitive and accurate and
      had a higher negative predictive value compared with clinical evaluation, ESR and
      CRP in predicting infection resolution or recurrence in patients with chronic
      bone and joint infections.

PMID- 21869729
TI  - Usefulness of combination of pulmonary ventilation and perfusion scintigraphy on
      the diagnosis of children with unilateral hyperlucent lung.
AB  - OBJECTIVES: Unilateral hyperlucent lung on chest radiograph is uncommon in
      children. It is often found incidentally and always refers to Swyer-James
      syndrome, with decrease in pulmonary vascularity and air trapping during
      expiration. However, it may occasionally mimic other serious lung diseases such
      as pulmonary hypoplasia/aplasia, defect of pulmonary artery, and other primary
      pulmonary disorders. In this study, we hypothesized that there would be
      characteristic patterns in pulmonary ventilation and perfusion scintigraphy (V/Q
      scan) in children with unilateral hyperlucency on chest film, which could play an
      important role in differential diagnosis of this disease group explicitly.
      METHODS: Children with unilateral hyperlucency on chest radiograph had a detailed
      clinical examination and underwent echocardiography, chest computed tomography,
      selective pulmonary angiogram, flexible bronchoscopy, and pulmonary V/Q scan.
      RESULTS: A total of 10 cases were enrolled, including two cases of unilateral
      pulmonary artery agenesis, three cases of Swyer-James syndrome, two cases of
      agenesis of the right lung, one case of lobar emphysema, and two cases of
      tetralogy of fallot with left pulmonary artery stenosis. Besides, an overview of
      children with unilateral hyperlucent lung is provided, reviewing nine studies
      (171 patients), including our clinical experience, and finally an algorithm for
      diagnosis unilateral hyperlucent lung is proposed, based on the characteristics
      of V/Q scan. CONCLUSION: We chose a descriptive approach to the V/Q scan in
      children with unilateral hyperlucent lung on chest radiograph. This result
      enables us to promote the V/Q scan as a first-line tool in evaluating these
      patients and to avoid further unnecessary procedures.

PMID- 21869730
TI  - Effect of folic acid intervention on the change of serum folate level in
      hypertensive Chinese adults:  do methylenetetrahydrofolate reductase and
      methionine synthase gene polymorphisms affect therapeutic responses?
AB  - OBJECTIVES: To assess the influence of individual methylenetetrahydrofolate
      reductase (MTHFR) C677T and methionine synthase A2756G polymorphisms on the
      change of serum folate concentration in response to different dosages and
      durations of folic acid (FA) supplementation in hypertensive Chinese adults.
      METHODS: A total of 480 patients with mild or moderate essential hypertension
      were randomly assigned to three treatment groups: (a) enalapril only (10 mg,
      control group); (b) enalapril FA tablet [10 : 0.4 mg (10 mg of enalapril combined
      with 0.4 mg of FA), low-FA group]; (c) enalapril FA tablet (10 : 0.8 mg, high-FA
      group), once daily for 8 weeks. Individual serum folate levels were measured at
      baseline, and at 4 and 8 weeks posttreatment. RESULTS: After 4 or 8 weeks of
      treatment, increases in serum folate were seen across all genotypes and FA dosage
      groups. However, compared with patients with 677CC genotype, those with CT or TT
      genotype in the low-FA group and TT genotype in the high-FA group still had
      significantly lower folate concentrations, particularly women. In the low-FA
      group, patients with CT or TT genotype showed an attenuated response compared
      with those with CC genotype (median ratio of folate at week 8 to that at
      baseline: CC,1.953 vs. CT,1.755 or TT,1.637, P<0.01 for both). Such an attenuated
      response was not observed in the high-FA group. Yet, only in the high-FA group
      did serum folate appear to reach a plateau after 4 weeks of treatment in all
      three MTHFR 677 genotypes and the methionine synthase 2756 AG/GG genotype.
      CONCLUSION: We demonstrated that MTHFR C677T polymorphisms can not only affect
      serum folate levels at the baseline and post-FA treatment, but also therapeutic
      responses to various dosages and durations of FA supplementation.

PMID- 21869731
TI  - Kidney-specific deletion of multidrug resistance-related protein 2 does not
      aggravate acute cyclosporine A nephrotoxicity in rats.
AB  - OBJECTIVE: Multidrug resistance-related protein 2 (Mrp2) is expressed in apical
      membranes of renal proximal tubular cells and contributes to the renal secretion
      of cyclosporine A (CsA). Mrp2-/- deficiency may lead to local renal CsA
      accumulation. We investigated whether kidney-specific Mrp2 deficiency enhances
      acute CsA nephrotoxicity in rats. METHODS: Kidney-specific Mrp2 deletion was
      achieved by bilateral nephrectomy and transplantation of a congenic Mrp2
      deficient kidney into wild-type recipients. Controls received a wild-type kidney.
      Animals were treated with CsA (10 or 30 mg/kg/day) for 7 days. Renal hemodynamics
      and renal cortical mRNA expression profile, oxidative stress, and the abundance
      of multidrug resistance protein 1 (Mdr1) and Mrp2 were assessed. RESULTS: CsA
      accumulation and CsA-induced reduction in glomerular filtration rate were similar
      in wild-type and Mrp2-/- kidneys. Renal vascular resistance and agonist-induced
      renal vascular responses were similar in both groups. A PCR array on 84 genes
      involved in the biotransformation and antioxidant defense revealed increased CsA
      induced mRNA expression of genes involved in oxidative and metabolic stress,
      inflammation, and apoptosis. This gene expression pattern was similar in wild
      type and Mrp2-/- kidneys. CsA increased the renal cortical oxidized glutathione,
      did not affect xanthine oxidase-dependent superoxide formation, and decreased
      renal cortical NADPH oxidase-dependent superoxide formation. Furthermore, CsA
      increased Mdr1 protein abundance to a greater extent in Mrp2-/- than in wild-type
      kidneys. CONCLUSION: Mrp2 is not critical for renal CsA disposition and its
      deficiency does not enhance acute CsA nephrotoxicity. The high Mdr1 abundance may
      at least in part prevent exaggerated CsA accumulation in Mrp2-/- kidneys.

PMID- 21869732
TI  - The human primary hepatocyte transcriptome reveals novel insights into
      atorvastatin and rosuvastatin action.
AB  - OBJECTIVES: With particular emphasis on interactions between cholesterol
      homeostasis and drug metabolism we investigate the transcriptome of human primary
      hepatocytes treated by two commonly prescribed cholesterol lowering drugs
      atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as
      well as a model substance for induction of nuclear pregnane X receptor. METHODS:
      Hepatocytes from human donors have been treated with rosuvastatin, atorvastatin,
      and rifampicin for 12, 24, and 48 h. Expression profiling with cholesterol and
      drug metabolism enriched low density Steroltalk cDNA and whole genome Affymetrix
      HG-U133 Plus 2.0 arrays has been applied. Differential expression (DE) of genes
      and gene set enrichment analysis of KEGG pathways were performed. Lists of
      differentially expressed genes and gene sets were cross-compared. Selected genes
      were confirmed by quantitative real-time PCR. RESULTS: Statins lead to: (a)
      upregulation of cholesterol-related genes indicating an increased LDL uptake and
      storage of esterified cholesterol, elevated bile acid/drug export and lower
      capacity to form HDL; (b) perturbation of genes in glucose and fatty acid
      homeostasis, influencing acetyl-CoA pools, promoting gluconeogenesis and glucose
      export; (c) elevated expression of ADIPOR2 suggesting increased sensitivity to
      adiponectin; (d) perturbations in genes of lipoprotein particle formation,
      differently for each statin; (e) perturbed expression of many metabolic genes
      that are directly controlled by nuclear receptors constitutive androstan and/or
      pregnane X. CONCLUSION: These data provide a novel global insight into hepatic
      effects of statins, offering biochemical explanations for higher blood glucose in
      statin-treated patients, and for drug-induced secondary fatty liver disease.

PMID- 21869734
TI  - Long-term nutrition and predictors of growth and weight gain following pediatric
      intestinal transplantation.
AB  - BACKGROUND: Advances in intestinal transplantation (ITx) have resulted in
      improved survival and the opportunity to examine nutritional outcomes. The aim of
      this study was to describe detailed, long-term nutritional results and identify
      positive predictors of growth and weight gain following pediatric ITx. METHODS: A
      single-center retrospective, Institutional Review Board-approved review of a
      prospective database was conducted. Inclusion criteria were ITx recipients 18
      years or younger with survival of 6 months or more. Outcomes included
      anthropometric measurements and biochemical markers at 6, 12, 24, 36, and 48
      months post-ITx. More than 25 ITx-related variables were analyzed as potential
      predictors of growth and weight gain. Statistical analysis was performed using
      chi-square test, t test, and analysis of variance. RESULTS: Between November 1991
      and April 2007, 50 children received 55 ITx; 33 patients met eligibility
      criteria. Median age at ITx was 2.2 years, follow-up time was 3.8 years, and time
      from ITx to cessation of total parenteral nutrition was 31 days. The most common
      micronutrient deficiencies post-ITx were zinc, iron, and copper. Serum protein
      levels improved significantly over time. Weight gain occurred within 6 months and
      vertical growth within 12 months, although limited catch-up growth was seen.
      Early predictors of weight gain and growth included shorter hospitalization and
      absence of rejection. Long-term predictors were low steroid dosage, infrequent
      hospitalization, and the use of peptide-based formulas. CONCLUSIONS: This
      represents one of the largest and most comprehensive long-term studies on
      nutritional outcomes in pediatric ITx. Overall, positive growth and weight gain
      were seen as were micronutrient deficiencies. Numerous long-term nutritional
      challenges exist which require a multidisciplinary approach and future
      prospective studies.

PMID- 21869735
TI  - Acute-on-chronic liver failure before liver transplantation: impact on
      posttransplant outcomes.
AB  - BACKGROUND: Acute decompensation in patients with chronic liver disease,
      resulting from acute kidney injury and infections, leads to significant morbidity
      and mortality. It is unclear whether patients who develop acute-on-chronic liver
      failure (ACLF) have poor outcomes after liver transplantation. METHODS: We
      performed a single-center retrospective cohort study of 332 patients to evaluate
      the effect of ACLF, defined as an acute rise in the Model for End-Stage Liver
      Disease score of more than 5 within 4 weeks before transplantation, on
      posttransplant outcomes including stage 4 chronic kidney disease, death,
      recurrent cirrhosis, or graft failure requiring retransplantation. RESULTS AND
      CONCLUSIONS: One hundred fifty-seven patients in the study had ACLF and 175
      patients had no ACLF (non-ACLF) pretransplant. Thirty-four patients in the entire
      cohort received dual organs, 10 of them (29.4%) had ACLF. Seventy-six percent of
      the patients with ACLF had acute kidney injury as their reason for decompensation
      and 23.6% had an infection. Mean Model for End-Stage Liver Disease score at
      transplant was significantly different between the groups (ACLF 28.77 vs. non
      ACLF 21.23, P<0.0001). A total of 16.6% of the patients achieved an estimated
      glomerular filtration rate (eGFR) less than 30 mL/min, 21% of patients died,
      12.3% developed cirrhosis, and 7.5% received a second transplant. There was no
      difference in mean eGFR between the ACLF and non-ACLF cohorts at 3 years
      posttransplant (56.35 mL/min vs. 59.93 mL/min, respectively, P=0.27). On
      multivariate analysis, ACLF was not significantly associated with eGFR less than
      30 mL/min, death, recurrent cirrhosis, or retransplantation when adjusted for
      potential confounders.

PMID- 21869733
TI  - Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.
AB  - OBJECTIVE: Responses to therapies, either with regard to toxicities or efficacy,
      are expected to involve complex relationships of gene products within the same
      molecular pathway or functional gene set. Therefore, pathways or gene sets, as
      opposed to single genes, may better reflect the true underlying biology and may
      be more appropriate units for analysis of pharmacogenomic studies. Application of
      such methods to pharmacogenomic studies may enable the detection of more subtle
      effects of multiple genes in the same pathway that may be missed by assessing
      each gene individually. METHODS: A gene set analysis of 3821 gene sets is
      presented assessing the association between basal messenger RNA expression and
      drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for
      two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and
      purines [6-thioguanine and 6-mercaptopurine]. RESULTS: The gene set nucleoside
      diphosphatase activity was found to be significantly associated with both dFdC
      and arabinoside, whereas gene set gamma-aminobutyric acid catabolic process was
      associated with dFdC and 6-thioguanine. These gene sets were significantly
      associated with the phenotype even after adjusting for multiple testing. In
      addition, five associated gene sets were found in common between the pyrimidines
      and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity
      and gamma-aminobutyric acid catabolic process) with a P value of less than
      0.0001. Functional validation was attempted with four genes each in gene sets for
      thiopurine and pyrimidine antimetabolites. All four genes selected from the
      pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one
      (PDE4D) was validated for the thiopurine gene sets. CONCLUSION: In summary,
      results from the gene set analysis of pyrimidine and purine therapies, used often
      in the treatment of various cancers, provide novel insight into the relationship
      between genomic variation and drug response.

PMID- 21869736
TI  - Coccidioidomycosis and lung transplantation.
AB  - Coccidioidomycosis, an endemic fungal infection in the desert southwestern United
      States, causes substantial morbidity and mortality in immunocompromised hosts.
      Because lungs are the primary site of coccidioidal infection, lung transplant
      recipients in endemic areas remain particularly vulnerable. Moreover, direct
      airway communication to the environment, diminished cough reflex, impaired
      mucociliary clearance, altered alveolar macrophage function, and ischemic lung
      injury further enhances the risk of pulmonary infection after lung
      transplantation. Herein, we review available data on coccidioidomycosis in solid
      organ transplant recipients and candidates seeking transplantation, and propose
      strategies for screening, treatment, and prevention of coccidioidal infection in
      the lung transplant candidate.

PMID- 21869737
TI  - To donate or not to donate: decision making and psychosocial determinants in
      living liver donation.

PMID- 21869738
TI  - Histologic recurrence of Henoch-Schonlein Purpura nephropathy after renal
      transplantation on routine allograft biopsy.
AB  - BACKGROUND: Henoch-Schonlein Purpura nephropathy (HSPN) recurrence in renal
      transplant recipients (RTRs) has been reported in 35% of patients, leading in 11%
      of these patients to graft loss at 5 years. However, its true incidence is
      unknown. The aim of this study was to investigate this recurrence incidence using
      routine allograft biopsies (RBs). METHODS: All RTRs with biopsy-proven HSP
      initial nephropathy were included (13 RTRs and 18 renal transplantations). At
      transplantation, the median age was 34 years, and 85% of RTRs were men. Overall,
      we analyzed 66 RBs that were routinely performed at 3 and 12 months after RT and
      when clinically indicated. Histologic recurrence was defined as the presence of
      IgA deposits within the mesangium and along the glomerular capillary walls.
      RESULTS: After a median follow-up of 83 months (range, 13-232 months;
      interquartile range, 26-235 months), histologic recurrence was detected in 69% of
      patients and in 61% of grafts after a mean period of 24 months (range, 1-156
      months). Clinical or biological signs were absent in all but one. Patient
      survival was 92.8%. Graft loss occurred in five cases, never were related to
      recurrence. At the last follow-up, the mean glomerular filtration rate was 48+/
      14.2 mL/min/1.73 m(2); in patients with and without recurrence, the mean rates
      were 52.1+/-17.5 and 42.4+/-5.3 mL/min/1.73 m(2), respectively (P=0.27).
      CONCLUSION: Histologic recurrence of HSPN after RT is frequently observed on
      routine RBs but is not associated with clinical consequences. The short-term
      prognosis of recurrence is good, but its long-term prognosis remains to be
      determined.

PMID- 21869739
TI  - Body composition and overweight of liver transplant recipients.
AB  - BACKGROUND: Overweight is often used as a description after liver transplantation
      (LTx), but studies on body composition of patients submitted to LTx have only
      been devoted to early postoperative periods; there is little information
      regarding abdominal obesity after LTx. The aim of this study was to assess body
      composition, body mass index (BMI), and waist circumference and verify the
      prevalence and risk factors for excessive weight, obesity, and abdominal obesity
      in long-term survivors of LTx. METHODS: Post-LTx patients with at least 1 year
      post-LTx were assessed for their body composition (by bioimpedance), BMI, and
      waist circumference. Demographic, socioeconomic, lifestyle, and clinical and
      dietetic variables were collected to assess risk factors using linear and
      logistic regression analyses. RESULTS: We evaluated 143 patients (51+/-13 years;
      59.4% male; median time since LTx: 4 years). The majority of patients had
      excessive weight, considering BMI, (58.1%). Considering body composition, 69.9%
      of patients were overweight and 37.8% obese. Some degree of abdominal obesity was
      seen in 88% of patients. Independent risk factors for overweight, obesity, and
      abdominal obesity after LTx included greater BMI before liver disease, weight
      gain since LTx, family history of overweight, smoking, working, being married,
      having less time since transplantation, a lower calcium intake, and less sleeping
      hours. CONCLUSIONS: The majority of patients are overweight or obese after LTx,
      and many of the associated risk factors are modifiable. Thus, patients,
      especially those who already have identified risk factors for overweight and
      obesity, undergoing LTx should be encouraged to engage in lifestyle changes
      early.

PMID- 21869740
TI  - Switching from calcineurin inhibitors to Mammalian target of rapamycin inhibitors
      -finally caught the right wave?

PMID- 21869741
TI  - Antibodies against nucleolin in recipients of organ transplants.
AB  - BACKGROUND: Patients who reject allografts frequently make strong antibody
      responses against donor human leukocyte antigens and autoantigens such as
      vimentin, collagen V, or alpha-tubulin and it has been postulated that
      autoantibodies may play a role in allograft failure. METHODS: We have used serum
      from patients who recently rejected an allograft as a source of antibodies in
      combination with lysates of human umbilical vein endothelial cells as a source of
      target antigens. Immunoprecipitation and protein identification was performed by
      mass spectrometry. Recombinant nucleolin was produced and sera were assayed for
      antibodies by enzyme-linked immunosorbent assay. RESULTS: Immunoprecipitation
      with serum WW led to the recognition of the protein nucleolin as a target
      antigen. By enzyme-linked immunosorbent assay, with recombinant nucleolin (r
      nucleolin), the frequency of antibodies to nucleolin were found to be 2.0% in
      normal subjects, 9.1% in patients waiting for a kidney transplant, 25.5% after
      irreversible rejection of a kidney allograft, 17.1% after a heart transplant, and
      43.8% in heart transplant recipients developing transplant-related coronary
      artery disease. Antibodies against nucleolin from mice or from transplant
      patients inhibited endothelial cell proliferation and in vitro capillary-like
      tube formation and caused apoptosis of human umbilical vein endothelial cells.
      CONCLUSIONS: Antibodies against nucleolin seem to inhibit and produce apoptosis
      of proliferating endothelial cells. These antibodies were found in many
      transplant patients and seemed to be associated with rejection of kidney
      allografts and with coronary artery disease in heart transplant recipients.

PMID- 21869742
TI  - Glial cell line-derived neurotrophic factor enhances human islet
      posttransplantation survival.
AB  - BACKGROUND: Development of pretransplantation islet culture strategies that
      preserve or enhance beta-cell viability would eliminate the requirement for the
      large numbers of islets needed to restore insulin independence in type 1 diabetes
      patients. We investigated whether glial cell line-derived neurotrophic factor
      (GDNF) could improve human islet survival and posttransplantation function in
      diabetic mice. METHODS: Human islets were cultured in medium supplemented with or
      without GDNF (100 ng/mL) and in vitro islet survival and function assessed by
      analyzing beta-cell apoptosis and glucose stimulated insulin release. In vivo
      effects of GDNF were assessed in streptozotocin-induced diabetic nude mice
      transplanted under the kidney capsule with 2000 islet equivalents of human islets
      precultured in medium supplemented with or without GDNF. RESULTS: In vitro, human
      islets cultured for 2 to 10 days in medium supplemented with GDNF showed lower
      beta-cell death, increased Akt phosphorylation, and higher glucose-induced
      insulin secretion than islets cultured in vehicle. Human islets precultured in
      medium supplemented with GDNF restored more diabetic mice to normoglycemia and
      for a longer period after transplantation than islets cultured in vehicle.
      CONCLUSIONS: Our study shows that GDNF has beneficial effects on human islet
      survival and could be used to improve islet posttransplantation survival.

PMID- 21869743
TI  - Feast or famine? The variable impact of coexisting fellowships on general surgery
      resident operative volumes.
AB  - OBJECTIVES: Nearly 80% of general surgery residents (GSR) pursue Fellowship
      training. We hypothesized that fellowships coexisting with general surgery
      residencies do not negatively impact GSR case volumes and that fellowship-bound
      residents (FBR) preferentially seek out cases in their chosen specialty ("early
      tracking"). METHODS: To test our hypotheses, we analyzed the Accreditation
      Council for Graduate Medical Education Surgical Operative Log data from 2009
      American Board of Surgery qualifying examination applicants (N = 976). General
      surgery programs coexisted with 35 colorectal (CR), 97 vascular (Vasc), 80
      minimally invasive (MIS), and 12 Endocrine (Endo) fellowships. We analyzed (1)
      operative cases for general surgery residency programs with and without
      coexisting Fellowships, comparing caseloads for FBR and all GSR and (2) operative
      cases of FBR in their chosen specialties compared to all other GSR. Group means
      were compared using ANOVA with significance set at P < 0.01. RESULTS: Coexisting
      fellowships had minimal impact on GSR caseloads. Endocrine fellowships actually
      enhanced case volumes for all residents. CR impact was neutral while MIS and
      vascular fellowships resulted in small declines. Endo, CR, and Vasc but not MIS
      FBR performed significantly more cases in their future specialties than their GSR
      counterparts, consistent with self-directed, prefellowship tracking. Tracking
      seems to be additive and FBR do not sacrifice other GSR cases. CONCLUSIONS: Our
      data establish that the impact of Fellowships on GSR caseloads is minimal. Our
      data confirm that FBR seek out cases in their future specialties ("early
      tracking").

PMID- 21869744
TI  - HLA antibody specification using single-antigen beads--a technical solution for
      the prozone effect.
AB  - BACKGROUND: Substantial progress in human leukocyte antigen antibody
      specification has been made by the introduction of Luminex single-antigen bead
      (SAB) assays. This progress was impaired when it turned out that this method is
      prone to a prozone effect leading to false-negative results in the case of high
      antibody titers. Testing serum and ethylenediaminetetraacetic acid (EDTA) plasma
      of one patient in parallel, we observed the prozone effect with the serum sample
      only. This led us to investigate complement component 1 (C1) as the cause of the
      prozone in SAB testing. We also found an easy way to overcome the prozone effect.
      METHODS: Sera with a prozone effect were tested in the SAB assay, applying
      different methods of serum pretreatment to explore the parameters leading to the
      prozone. RESULTS: The prozone was not observed when EDTA plasma or serum with
      EDTA added were tested. Further, addition of dithiothreitol, addition of C1
      inhibitor, or heat inactivation of the sera abolished the prozone effect. Adding
      fresh nonimmune serum to heat-inactivated sera restored the prozone effect. Only
      beads showing a prozone were found to be covered with C1q. CONCLUSION: Our
      observations are consistent with the hypothesis that dissociation or destruction
      of complement C1 eliminates the prozone effect. Addition of EDTA to serum of
      highly immunized patients is the easiest way to avoid false-negative results in
      SAB testing caused by a prozone effect.

PMID- 21869745
TI  - Impact of hepatitis C virus infection on the risk of infectious complications
      after kidney transplantation: data from the RESITRA/REIPI cohort.
AB  - BACKGROUND: There is scarce information regarding the role of hepatitis C virus
      (HCV) infection in the development of infectious complications after kidney
      transplantation (KT). METHODS: We prospectively analyzed all KT recipients
      included in the Spanish Network for the Research of Infection in Transplantation
      cohort from September 2003 to February 2005 with a posttransplant follow-up of 3
      years and compared the incidence of both overall and specific infections
      according to the pretransplant anti-HCV antibody status. RESULTS: Of 1302
      analyzed recipients, 105 (8.1%) were anti-HCV positive. These patients presented
      a higher rate of previous transplant (P<0.001), had a lower donor age (P=0.055),
      higher transfusion requirements (P=0.037), and more frequently received induction
      therapy with antithymocyte antibodies (P=0.005). We found no differences between
      anti-HCV-positive and -negative recipients in the overall incidence rate of
      infection (0.82 vs. 0.74 episodes per 1000 transplant-days, respectively).
      Nevertheless, anti-HCV-positive recipients had a higher cumulative incidence of
      bloodstream (P=0.01) and upper urinary tract infections (P=0.037). Anti-HCV
      status emerged by logistic regression as an independent risk factor only for
      bloodstream infection (odds ratio, 3.14; 95% confidence interval, 1.19-8.24;
      P=0.020). Anti-HCV-positive recipients also experimented a higher rate of
      recurrent acute rejection (P=0.045) and retransplantation (P=0.017), with no
      differences in overall mortality. CONCLUSIONS: According to the results of the
      Spanish Network for the Research of Infection in Transplantation cohort, the
      incidence of some potentially severe posttransplant infections may be increased
      in anti-HCV-positive KT recipients.

PMID- 21869746
TI  - En bloc kidney transplantation from pediatric donors: comparable outcomes with
      living donor kidney transplantation.
AB  - BACKGROUND: En bloc kidneys from pediatric donors have been considered suboptimal
      for transplantation to adult recipients and their outcomes have rarely been
      compared with living donor kidney transplantation (LDKT). Traditionally, there
      has been hesitancy in transplanting en bloc kidneys from donors weighing less
      than 10 kg due to high risk of technical complications. METHODS: Retrospective
      chart reviews were performed to compare outcomes after pediatric en bloc (n=20,
      mean donor weight 11.4 kg), standard criteria deceased (n=249), and living donor
      (n=215) kidney transplantation in adult recipients at our center. The outcomes
      after en bloc transplantation from young donors weighing less than or equal to 10
      kg were compared with those from 11 to 15 kg donors. RESULTS: The 5-year graft
      survival after en bloc, standard deceased, and LDKT were 92%, 70%, and 88%,
      respectively (P=ns). There were no vascular complications, and urine leak was
      seen in 1 of 20 en bloc transplants. The 1-year serum creatinine of 1.1+/-0.2
      mg/dL in recipients from less than or equal to 10 kg donors was comparable with
      0.9+/-0.5 mg/dL in 11 to 15 kg group (P=ns). CONCLUSIONS: Excellent long-term
      outcome after pediatric en bloc kidney transplantation from donors weighing less
      than or equal to 15 kg are comparable with those after LDKT. By using meticulous
      surgical technique and judicious recipient selection criteria, technical graft
      losses can be minimized when using en bloc pediatric kidneys from donors weighing
      less than or equal to 10 kg. Use of pediatric en bloc kidneys should be
      encouraged continuously to address the problem of organ shortage.

PMID- 21869747
TI  - Identification of dehydroxytrichostatin A as a novel up-regulator of the ATP
      binding cassette transporter A1 (ABCA1).
AB  - The ATP-binding cassette transporter A1 (ABCA1) mediates the cellular efflux of
      excess cholesterol and phospholipids to lipid-poor apolipoprotein A-I (apoA-I).
      ABCA1 plays an important role in high-density lipoprotein (HDL) biogenesis and
      reverse cholesterol transport. By using a cell-based screening model for the
      ABCA1 up-regulator and column chromatography, an active compound, 9179B, was
      isolated. Through analysis of its NMR data, 9179B was identified as
      dehydroxytrichostatin A. We found that 9179B increased the transcription of ABCA1
      in a cell-based reporter assay, with an EC(50) value of 2.65 MUM. 9179B up
      regulated ABCA1 expression at both mRNA and protein levels in HepG2 and RAW264.7
      cells. It also up-regulated the expression of scavenger receptor class B type I
      (SR-BI) as well as the uptake of DiI-HDL in RAW264.7 cells. This compound
      stimulated ApoA-I-mediated cellular cholesterol efflux from RAW 264.7 cells. We
      further found that 9179B was a potent histone deacetylase (HDAC) inhibitor with
      an IC(50) value of 0.08 MUM. Reporter gene assays showed that the regulation of
      ABCA1 transcription by 9179B was mainly mediated by the -171/-75 bp promoter
      region. Together, our results indicate that 9179B is an ABCA1 up-regulator and
      dehydroxytrichostatin A may be a novel anti-atherogenic compound.

PMID- 21869748
TI  - Chirality and numbering of substituted tropane alkaloids.
AB  - The strict application of IUPAC rules for the numbering of tropane alkaloids is
      not always applied by authors and there is hence a lot of confusion in the
      literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has
      been chosen arbitrarily, based on NMR and MS data, without taking into account
      the absolute configuration of these two carbons. This paper discusses the problem
      and the relevance of CD and NMR to determine molecular configurations. We report
      on the use of (1)H-NMR anisochrony (Deltadelta) induced by the Mosher's chiral
      auxiliary reagents (R)-(-)- and (S)-(+)-alpha-methoxy-alpha-trifluoromethyl
      phenylacetyl chlorides (MTPA-Cl), to determine the absolute configuration of
      (3R,6R)-3alpha-hydroxy-6beta-senecioyloxytropane, a disubstituted tropane
      alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae).
      These analytical tools should help future works in correctly assigning the
      configuration of additional 3, 6/7 disubstituted tropane derivatives.

PMID- 21869749
TI  - Effect of ASP2151, a herpesvirus helicase-primase inhibitor, in a guinea pig
      model of genital herpes.
AB  - ASP2151 is a herpesvirus helicase-primase inhibitor with antiviral activity
      against varicella zoster virus and herpes simplex virus types 1 (HSV-1) and 2
      (HSV-2). Here, we examined the potency and efficacy of ASP2151 against HSV in
      vitro and in vivo. We found that ASP2151 was more potent in inhibiting the
      replication of HSV-1 and HSV-2 in Vero cells in the plaque reduction assay and
      had greater anti-HSV activity in a guinea pig model of genital herpes than did
      acyclovir and valacyclovir (VACV), respectively. Oral ASP2151 given from the day
      of infection reduced peak and overall disease scores in a dose-dependent manner,
      resulting in complete prevention of symptoms at the dose of 30 mg/kg. The 50%
      effective dose (ED(50)) values for ASP2151 and VACV were 0.37 and 68 mg/kg,
      respectively, indicating that ASP2151 was 184-fold more potent than VACV. When
      ASP2151 was administered after the onset of symptoms, the disease course of
      genital herpes was suppressed more effectively than by VACV, with a significant
      reduction in disease score observed one day after starting ASP2151 at 30 mg/kg,
      whereas the therapeutic effect of VACV was only evident three days after
      treatment at the highest dose tested (300 mg/kg). This indicated that ASP2151
      possesses a faster onset of action and wider therapeutic time window than VACV.
      Further, virus shedding from the genital mucosa was significantly reduced with
      ASP2151 at 10 and 30 mg/kg but not with VACV, even at 300 mg/kg. Taken together,
      our present findings demonstrated the superior potency and efficacy of ASP2151
      against HSV.

PMID- 21869750
TI  - Flow injection spectrophotometric determination of N-acetyl-L-cysteine as a
      complex with palladium(II).
AB  - We describe a new method using flow-injection analysis with spectro-photometric
      detection, suitable for the determination of N-acetyl-L-cysteine (NAC). The
      proposed method is appropriate for the determination of NAC in reaction with
      Pd(2+) ions in the concentration range from 1.0 * 10(-5) mol L(-1) to 6.0 * 10(
      5) mol L(-1). The detection limit NAC was 5.84 * 10(-6) mol L(-1) and the
      recorded relative standard deviation of the method is in the range from 1.67 to
      4.11%. NAC and Pd(2+) form complexes of Pd(2+):NAC molar ratios of 1:1 and 1:2,
      depending on the ratio of their analytical concentrations. The cumulative
      conditional stability constant for the Pd(NAC)(2)(2+) complex is beta(12)' = 2.69
      * 10(9) L(2) mol(-2). The proposed method was compared with the classic
      spectrophotometric determination of NAC, using the same reagent, PdCl(2), and had
      shown certain advantages: a) shorter analysis time; b) the use of smaller volumes
      of sample and reagents, which make the proposed method cheaper and faster for NAC
      determination in real samples without sample pretreatment.

PMID- 21869751
TI  - Synthesis of silver nanoparticles in chitosan, gelatin and chitosan/gelatin
      bionanocomposites by a chemical reducing agent and their characterization.
AB  - In this research, silver nanoparticles (AgNPs) were synthesized in chitosan
      (Cts), Cts/gelatin and gelatin suspensions using a chemical reducing agent. Cts
      and gelatin were used as natural stabilizers and solid support, whereas AgNO(3)
      was used as the silver precursor. Sodium borohydride (NaBH(4)) was used as the
      reducing agent. The properties of AgNPs in Cts, Cts/gelatin and gelatin
      bionanocomposites (BNCs) were studied in terms of their surface plasmon
      resonance, crystalline structure, average diameter size, particle distributions,
      surface topography and functional groups. All the samples were characterized by
      UV-visible spectroscopy, powder X-ray diffraction, transmission electron
      microscopy, atomic force microscopy and Fourier transform infrared spectroscopy.

PMID- 21869752
TI  - A novel cyclodione coumarin from the stem bark of Mesua beccariana.
AB  - Our ongoing investigations on the stem bark of Mesua beccariana afforded a novel
      cyclodione coumarin, beccamarin, together with two known xanthones, mesuarianone,
      mesuasinone, two anthraquinones, 4-methoxy-1,3,5-trihydroxy-anthraquinone and 2,5
      dihydroxy-1,3,4-trimethoxyanthraquinone and one coumarin, mammea A/AB. The
      structures were elucidated by 1D and 2D NMR and MS techniques.

PMID- 21869753
TI  - Use of graphite oxide and graphene oxide as catalysts in the synthesis of
      dipyrromethane and calix[4]pyrrole.
AB  - Graphite oxide and graphene oxides have been used as solid catalysts for the
      synthesis of 5,5-dialkyldipyrromethanes and calix[4]pyrroles in organic and
      aqueous solutions at room temperature.

PMID- 21869754
TI  - Cyclization vs. cyclization/dimerization in o-amidostilbene radical cation
      cascade reactions: the amide question.
AB  - The n-butyramido, isobutyramido, benzamido, and furancarboxamido functions
      profoundly modulate the electronics of the stilbene olefinic and NH groups and
      the corresponding radical cations in ways that influence the efficiency of the
      cyclization due presumably to conformational and stereoelectronic factors. For
      example, isobutyramido- stilbene undergoes FeCl(3) promoted cyclization to
      produce only indoline, while n-butyramidostilbene, under the same conditions,
      produces both indoline and bisindoline.

PMID- 21869755
TI  - Use of balance methods for assessment of short-term changes in body composition.
AB  - Balance methods reveal changes in body energy, nitrogen, macro- and
      micronutrients as well as fluid in response to different feeding regimens. Under
      metabolic ward conditions, where physical activity is restricted and activity and
      food intake are controlled, the errors of estimates of energy intake, energy
      expenditure, and energy losses are about 2, 4, and 2%, respectively. Balance
      techniques can be used to validate techniques of in vivo body composition
      analysis (BCA). This is necessary since immediate and transient changes in body
      composition in response to a change in diet adversely affect the validity of
      techniques by violating the assumptions underlying standard methods (i.e., a
      constant composition or hydration of lean mass). Using two compartment reference
      methods, like densitometry, dual X-ray absorptiometry (DXA) or deuterium
      dilution, changes in fat mass with caloric restriction and overfeeding can be
      measured with a minimal detectable change (MDC) of 1.0-2.0 kg. However, when
      compared against balance data, the validity of these techniques to measure short
      term changes in body composition is poor. The noninvasive and rapid new
      quantitative magnetic resonance (QMR) technique has a high precision with a MDC
      of 0.18 kg of fat mass. The validity of QMR to assess short-term changes in fat
      mass is challenged by comparison to balance data. Today, techniques used for in
      vivo BCA should be related to steady state conditions only, while in the
      nonsteady state, the use of balance methods is recommended to assess short-term
      changes in body composition.

PMID- 21869756
TI  - Diastolic dysfunction and intraventricular dyssynchrony are restored by low
      intensity exercise training in obese men.
AB  - The aim of this study was to evaluate the impact of a low-intensity training
      program on subclinical cardiac dysfunction and on dyssynchrony in moderately
      obese middle aged men. Ten obese and 14 age-matched normal-weight men (BMI: 33.6
      +/- 1.0 and 24.2 +/- 0.5 kg/m(2)) were included. Obese men participated in an 8
      week low-intensity training program without concomitant diet. Cardiac function
      and myocardial synchrony were assessed by echocardiography with tissue Doppler
      imaging (TDI) and speckle tracking echocardiography (STE). At baseline, obese men
      showed diastolic dysfunction on standard echocardiography, lower strain values
      (systolic strain: 15.9 +/- 0.9 vs. 18.8 +/- 0.3%, diastolic strain rate: 0.81 +/-
      0.09 vs. 1.05 +/- 0.06 s(-1)), and significant intraventricular dyssynchrony
      (systolic: 13.3 +/- 2.1 vs. 5.4 +/- 2.1 ms, diastolic: 17.4 +/- 3.2 vs. 9.1 +/-
      2.1 ms) (P < 0.05 vs. controls for all variables). Training improved aerobic
      fitness, decreased systolic blood pressure and heart rate, and reduced fat mass
      without weight loss. Diastolic function, strain values (systolic strain: 17.4 +/-
      0.9%, diastolic strain rate: 0.96 +/- 0.12 s(-1)) and intraventricular
      dyssynchrony (systolic: 3.3 +/- 1.7 ms, diastolic: 5.5 +/- 3.4 ms) improved
      significantly after training (P < 0.05 vs. baseline values for all variables),
      reaching levels similar to those of normal-weight men. In conclusion, in obese
      men, a short and easy-to-perform low intensity training program restored
      diastolic function and cardiac synchrony and improved body composition without
      weight loss.

PMID- 21869757
TI  - A population-based twin study on sleep duration and body composition.
AB  - The aim of this study is to investigate the relationship between sleep duration
      and body composition and to estimate the genetic contribution of sleep duration
      and body composition in a Chinese twin population. This cross-sectional analysis
      included 738 men and 511 women aged 21-72 year. Anthropometric and dual-energy X
      ray absorptiometry (DXA) measures of body composition were used. Sleep duration
      was obtained from a standard sleep questionnaire. Multiple regression models were
      used to examine the association between sleep duration and body composition
      measures. Structural equation modeling was used to assess the heritability of
      sleep duration and body composition. Compared with individuals in the 2nd and 3rd
      age-specific quartiles of sleep duration (reference group), shorter (1st
      quartile) sleep duration among women but not men was associated with higher z
      scores (0.248-0.317) for all adiposity measures--BMI, fat mass index (FMI),
      percent body fat mass (%BF), and percent trunk fat mass (%TF), P < 0.05 for each-
      and with 0.306 lower z-scores for percent body lean mass (%LM) and 0.353 lower
      lean/fat mass ratio (LFR), P < 0.01 for each. The heritability of sleep duration
      was 0.27 in men and 0.29 in women, while the heritability of body composition was
      as high as 0.56-0.73 after adjustment for age in both genders. Short sleep
      duration was associated with increased body fat and decreased lean body mass in
      women but not in men. Sleep duration was largely influenced by environmental
      factors while adiposity measures were mainly influenced by genetic factors.

PMID- 21869758
TI  - Quinoa extract enriched in 20-hydroxyecdysone protects mice from diet-induced
      obesity and modulates adipokines expression.
AB  - Besides their well-known effect in the molting control in insects, ecdysteroids
      are steroid hormones that display potential pharmacologic and metabolic
      properties in mammals. The most common ecdysteroid, 20-hydroxyecdysone (20E) is
      found in many plants such as quinoa. The aim of the present study was to
      investigate the ability of quinoa extract (Q) enriched in 20E supplementation to
      prevent the onset of diet-induced obesity and to regulate the expression of
      adipocyte-specific genes in mice. Mice were fed a standard low-fat (LF) or a high
      fat (HF) diet with or without supplementation by 20E-enriched Q or pure 20E for 3
      weeks. Supplementation with Q reduced adipose tissue development in HF mice
      without modification of their body weight gain. This adipose tissue-specific
      effect was mainly associated with a reduced adipocyte size and a decrease in the
      expression of several genes involved in lipid storage, including lipoprotein
      lipase and phosphoenolpyruvate carboxykinase. Furthermore, Q-treated mice
      exhibited marked attenuation of mRNA levels of several inflammation markers
      (monocyte chemotactic protein-1, CD68) and insulin resistance (osteopontin,
      plasminogen activator inhibitor-1 (PAI-1)) as compared to HF mice. Q
      supplementation also reversed the effects of HF-induced downregulation of the
      uncoupling protein(s) (UCP(s)) mRNA levels in muscle. Similar results were
      obtained in mice fed a HF diet supplemented with similar amounts of pure 20E,
      suggesting that the latter accounted for most of the Q effects. Our study
      indicates that Q has an antiobesity activity in vivo and could be used as a
      nutritional supplement for the prevention and treatment of obesity and obesity
      associated disorders.

PMID- 21869759
TI  - Human monocytes accelerate proliferation and blunt differentiation of
      preadipocytes in association with suppression of C/EBPAlpha mRNA.
AB  - Obesity, type 2 diabetes, and HIV-associated lipodystrophy are associated with
      abnormalities in adipocyte growth and differentiation. In persons with these
      conditions, adipose depots contain increased numbers of macrophages, but the
      origins of these cells and their specific effects are uncertain. Peripheral blood
      mononuclear cells (PBMC)-derived monocytes, but not T cells, cocultured via
      transwells with primary subcutaneous preadipocytes, increased proliferation
      (approximately twofold) and reduced differentiation (~50%) of preadipocytes. Gene
      expression analyses in proliferating preadipocytes (i.e., prior to hormonal
      induction of terminal differentiation) revealed that monocytes down-regulated
      mRNA levels of CCAAT/enhancer binding protein, alpha (C/EBPalpha) and up
      regulated mRNA levels of G0/G1 switch 2 (G0S2) message, genes important for the
      regulation of adipogenesis and the cell cycle. These data indicate that
      circulating peripheral blood monocytes can disrupt adipogenesis by interfering
      with a critical step in C/EBPalpha and G0S2 transcription required for
      preadipocytes to make the transition from proliferation to differentiation.
      Interactions between preadipocytes and monocytes also increased the inflammatory
      cytokines IL-6 and IL-8, as well as a novel chemotactic cytokine, CXCL1.
      Additionally, the levels of both IL-6 and CXCL1 were highest when preadipocytes
      and monocytes were cultured together, compared to each cell in culture alone.
      Such cross-talk amplifies the production of mediators of tissue inflammation.

PMID- 21869761
TI  - Secular trends in the diagnosis and treatment of obesity among US adults in the
      primary care setting.
AB  - Excess weight afflicts the majority of the US adult population. Research suggests
      that the role of primary care physicians in reducing overweight and obesity is
      essential; moreover, little is known about self-care of obesity. This report
      assessed the secular trends in the care of overweight and investigated the
      secular association between obesity with care of overweight in primary care and
      self-care of overweight. Cross-sectional evaluation of the National Health and
      Nutrition Examination Survey (NHANES) III (1988-1994) and the Continuous NHANES
      (1999-2008) was employed; the total sample comprised 31,039 nonpregnant adults
      aged 20-90 years. The relationship between diagnosed overweight, and directed
      weight loss with time and obesity was assessed. Despite the combined secular
      increase in the prevalence of overweight and obesity (BMI >25.0 kg/m(2)) between
      1994 and 2008 (56.1-69.1%), there was no secular change in the odds of being
      diagnosed overweight by a physician when adjusted for covariates; however,
      overweight and obese individuals were 40 and 42% less likely to self-diagnose as
      overweight, and 34 and 41% less likely to self-direct weight loss in 2008
      compared to 1994, respectively. Physicians were also significantly less likely to
      direct weight loss for overweight and obese adults with weight-related
      comorbidities across time (P < 0.05). Thus, the surveillance of secular trends
      reveals that the likelihood of physician- and self-care of overweight decreased
      between 1994 and 2008 and further highlights the deficiencies in the management
      of excess weight.

PMID- 21869762
TI  - OMG do not say LOL: obese adolescents' perspectives on the content of text
      messages to enhance weight loss efforts.
AB  - Adolescents participating in weight loss programs experience difficulty adhering
      to behavior change recommendations. Communications technology provides a low cost
      means to increase the frequency of contact with adolescents which can improve
      their engagement and also lead to behavior change. Within a larger project on the
      development of tailored text messages for adolescents enrolled in an existing
      multidisciplinary weight management program, this study explored participants'
      perspectives about message content. A library of messages was developed focused
      on topics central to weight management. Four focus groups were conducted with a
      total of 24 participants from the weight management program to gage their
      reactions to the messages. Detailed notes from the focus groups were analyzed to
      assess the acceptability of individual messages and to identify overriding
      themes. Results indicate that participants were very enthusiastic about receiving
      text messages. They preferred messages that provided recipe ideas, included
      successful weight loss strategies used by peers, and requested feedback regarding
      their progress. They preferred positive, encouraging, and direct messages. They
      were unanimous that messages should include encouraging symbols (e.g.,
      exclamation points and "smiley faces") as often as possible. They emphasized that
      any mention of unhealthy foods or behaviors would trigger them to eat those foods
      or engage in those behaviors. Text messaging acronyms (e.g., LOL) were considered
      too informal for messages from healthcare providers. This study suggests that
      including text messages in obesity interventions is acceptable to obese
      adolescents as a means of supporting their weight loss efforts, and it highlights
      the need for such messages to be carefully constructed.

PMID- 21869763
TI  - Impaired insulin sensitivity and elevated ectopic fat in healthy obese vs.
      nonobese prepubertal children.
AB  - Insulin sensitivity is impaired and ectopic fat (accretion of lipids outside of
      typical adipose tissue depots) increased in obese adults and adolescents. It is
      unknown how early in life this occurs; thus, it is important to evaluate young
      children to identify potential factors leading to the development of metabolic
      syndrome. We examined an ethnically diverse cohort of healthy, exclusively
      prepubertal children (N = 123; F = 57, M = 66; age 8.04 +/- 0.77 years) to
      examine differences in insulin sensitivity and ectopic and visceral fat
      deposition between obese and nonobese youth. Obesity was categorized by age- and
      sex-adjusted BMI z-scores (nonobese = z-score <2 (N = 94) and obese = z-score >=2
      (N = 29)). Insulin sensitivity was assessed by both a frequently sampled
      intravenous glucose tolerance test (S(i)) and the homeostatic model assessment of
      insulin resistance (HOMA(IR)). Intramyocellular lipids (IMCLs) from soleus and
      intrahepatic lipids (IHLs) were assessed by magnetic resonance spectroscopy,
      visceral adipose tissue (VAT) by magnetic resonance imaging, and total body fat
      by dual-energy X-ray absorptiometry. We also examined serum lipids (total
      cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low
      density lipoprotein cholesterol) and blood pressure (diastolic and systolic).
      Obese children exhibited significantly lower S(i) (5.9 +/- 5.98 vs. 13.43 +/-
      8.18 (mu/l)(-1).min(-1), P = 0.01) and HDL-C and higher HOMA(IR) (1.68 +/- 1.49
      vs. 0.63 +/- 0.47, P < 0.0001), IMCL (0.74 +/- 0.39 vs. 0.44 +/- 0.21% water
      peak, P < 0.0001), IHL (1.49 +/- 1.13 vs. 0.54 +/- 0.42% water peak, P < 0.0001),
      VAT (20.16 +/- 8.01 vs. 10.62 +/- 5.44 cm(2), P < 0.0001), total cholesterol,
      triglycerides, low-density lipoprotein cholesterol, and systolic blood pressure
      relative to nonobese children. These results confirm significantly increased
      ectopic fat and insulin resistance in healthy obese vs. nonobese children prior
      to puberty. Excessive adiposity during early development appears concomitant with
      precursors of type 2 diabetes and the metabolic syndrome.

PMID- 21869764
TI  - Relationship between the Bertin index to estimate visceral adipose tissue from
      dual-energy X-ray absorptiometry and cardiometabolic risk factors before and
      after weight loss.
AB  - The purpose of this study was to investigate the relationship between visceral
      adipose tissue (VAT), estimated with the Bertin index obtained from dual-energy X
      ray absorptiometry (DXA), with cardiometabolic risk factors before and after a
      weight loss program and compare it with VAT measured with computed tomography
      (CT) scan. The study population for this analysis included 92 nondiabetic
      overweight and obese sedentary postmenopausal women (age: 58.1 +/- 4.7 years,
      BMI: 31.8 +/- 4.2 kg/m(2)) participating in a weight loss intervention that
      consisted of a caloric restricted diet with and without resistance training (RT).
      We measured (i) VAT using CT scan, (ii) body composition (using DXA) from which
      the Bertin index was calculated, (iii) cardiometabolic risk factors such as
      insulin sensitivity (using the hyperinsulinenic-euglycemic clamp technique), peak
      oxygen consumption, blood pressure, plasma lipids, C-reactive protein as well as
      fasting glucose and insulin. VAT levels for both methods significantly decreased
      after the weight loss intervention. Furthermore, no differences in VAT levels
      between both methods were observed before (88.0 +/- 25.5 vs. 83.8 +/- 22.0 cm(2))
      and after (76.8 +/- 27.8 vs. 73.6 +/- 23.2 cm(2)) the weight loss intervention.
      In addition, the percent change in VAT levels after the weight loss intervention
      was similar between both methods (-13.0 +/- 16.5 vs. -12.5 +/- 12.6%). Moreover,
      similar relationships were observed between both measures of VAT with
      cardiometabolic risk factors before and after the weight loss intervention.
      Finally, results from the logistic regression analysis consistently showed that
      fat mass and lean body mass were independent predictors of pre- and post-VAT
      levels for both methods in our cohort. In conclusion, estimated visceral fat
      levels using the Bertin index may be able to trace variations of VAT after weight
      loss. This index also shows comparable relationships with cardiometabolic risk
      factors when compared to VAT measured using CT scan.

PMID- 21869765
TI  - Update on the pharmacologic management of neonatal abstinence syndrome.
AB  - Although a statement on Neonatal Drug Withdrawal was published in 1998 by the
      American Academy of Pediatrics, pharmacologic management of neonatal abstinence
      syndrome (NAS) remains a challenge. Published clinical trials are limited,
      restricting treatment decision making to practitioner's experience and preference
      rather than evidence-based medicine. To optimize withdrawal symptom prevention,
      drug selection is often based on the offending agent (opioids versus
      polysubstance exposure), clinical presentation, mechanism of action (agonist
      versus partial agonist/antagonist, receptor effects), pharmacokinetic parameters
      and available drug formulations. This review addresses risk factors and
      pathophysiology of NAS, summarizes parameters of common drugs used for the
      management of NAS, and reviews published literature of standard therapies as well
      as newer agents. Based on the current literature, paregoric is no longer
      recommended and oral morphine solutions remain the mainstay of therapy for opiate
      withdrawal. Other potential therapies include methadone, buprenorphine,
      phenobarbital and clonidine with the latter two agents as adjunctive therapies.

PMID- 21869766
TI  - White-gray matter echogenicity ratio and resistive index: sonographic bedside
      markers of cerebral hypoxic-ischemic injury/edema?
AB  - OBJECTIVE: Head ultrasonography (HUS) is a reliable and easy to perform bedside
      imaging technique that can give valuable information about degree of brain
      injury/edema after perinatal asphyxia in term neonates. The goals of our study
      were to determine whether semiquantitative markers such as standardized white
      matter/gray matter (WM/GM) echogenicity ratio and resistive index (RI) value
      measured by HUS differs between asphyxiated term neonates and healthy controls.
      STUDY DESIGN: Thirty-one carefully selected term neonates who suffered from
      perinatal hypoxic-ischemic encephalopathy (HIE) were included in the study. The
      ratio of the WM/GM echogenicity of the cingulate gyrus was calculated. In
      addition, the RI value was measured in the anterior cerebral artery. US scalars
      were compared with 11 healthy neonates. RESULT: WM/GM ratio is significantly
      increased and RI value significantly decreased in asphyxiated term neonates
      compared with healthy subjects. CONCLUSION: WM/GM ratio and RI value allows
      discriminating between asphyxiated neonates and healthy subjects. These US
      scalars may serve as valuable, easy to acquire semiquantitative bedside markers
      of brain HIE, when magnetic resonance imaging is unavailable or cannot be
      performed in the acute setting.

PMID- 21869760
TI  - Reliability and intermethod agreement for body fat assessment among two field and
      two laboratory methods in adolescents.
AB  - To increase knowledge about reliability and intermethods agreement for body fat
      (BF) is of interest for assessment, interpretation, and comparison purposes. It
      was aimed to examine intra- and inter-rater reliability, interday variability,
      and degree of agreement for BF using air-displacement plethysmography (Bod-Pod),
      dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA),
      and skinfold measurements in European adolescents. Fifty-four adolescents (25
      females) from Zaragoza and 30 (14 females) from Stockholm, aged 13-17 years
      participated in this study. Two trained raters in each center assessed BF with
      Bod-Pod, DXA, BIA, and anthropometry (DXA only in Zaragoza). Intermethod
      agreement and reliability were studied using a 4-way ANOVA for the same rater on
      the first day and two additional measurements on a second day, one each rater.
      Technical error of measurement (TEM) and percentage coefficient of reliability
      (%R) were also reported. No significant intrarater, inter-rater, or interday
      effect was observed for %BF for any method in either of the cities. In Zaragoza,
      %BF was significantly different when measured by Bod-Pod and BIA in comparison
      with anthropometry and DXA (all P < 0.001). The same result was observed in
      Stockholm (P < 0.001), except that DXA was not measured. Bod-Pod, DXA, BIA, and
      anthropometry are reliable for %BF repeated assessment within the same day by the
      same or different raters or in consecutive days by the same rater. Bod-Pod showed
      close agreement with BIA as did DXA with anthropometry; however, Bod-Pod and BIA
      presented higher values of %BF than anthropometry and DXA.

PMID- 21869767
TI  - Utility of intramuscular antibiotics for secondary prevention of early onset,
      asymptomatic 'suspected' neonatal sepsis.
AB  - OBJECTIVE: To evaluate the safety, efficacy and cost-benefit of intramuscular
      (IM) antibiotics administration in the secondary prevention of suspected neonatal
      sepsis in asymptomatic term neonates. STUDY DESIGN: Retrospective review of
      inborn asymptomatic full-term neonates with birth weights >=2000 g who required
      sepsis evaluation and treatment with IM antibiotics were undertaken from July
      2001 to July 2008. The IM antibiotic protocol was categorized as inadequate if
      the neonate became symptomatic, had positive blood or cerebrospinal fluid (CSF)
      cultures or was readmitted for sepsis within 2 weeks of nursery discharge. Data
      were analyzed to identify relationships between key indicators for the presence
      of neonatal bacterial infection, 'inadequate IM antibiotics protocol' and the
      rehospitalization rates. RESULT: There were 29 698 infants admitted to the
      newborn nursery (NBN) during the study period. A total of 5045 infants (17%) were
      evaluated for suspected neonatal sepsis; 421 neonates (8.3%) were treated with IM
      antibiotics for 48 to 72 h. Fourteen infants (3.3%) met criteria for 'inadequate
      IM antibiotics protocol'. Seven infants developed symptoms within the first 32 h
      of life, and seven infants had positive blood or CSF cultures, one of whom
      required rehospitalization. None of the infants were hemodynamically unstable or
      developed complications, including adverse events associated with IM drug
      administration. CONCLUSION: Use of IM antibiotics is a safe alternative to
      intravenous antibiotics in the secondary prevention of asymptomatic term newborns
      with presumed sepsis. There is a substantial cost savings in caring for
      asymptomatic neonates with presumed sepsis in the NBN compared with neonatal
      intensive care unit costs.

PMID- 21869768
TI  - What motivates dentists to work in prisons? A qualitative exploration.
AB  - OBJECTIVE: To explore what motivates dentists to work in prisons using Vroom's
      theoretical model of motivation as an explanatory framework. METHOD: In-depth
      interviews were conducted with ten of the 15 dentists working in Scottish
      prisons. The focus was to explore their motivations to work in Scottish prisons.
      The data were analysed using a thematic framework based on the three motivational
      dimensions of expectancy, instrumentality and valence. RESULTS: The dentists had
      the skills to help improve their prisoner-patients' oral health but their efforts
      were often hindered by institutional rationing and the requirement to fit in with
      prison routines and procedures (expectancy). Despite these institutional
      difficulties the dentists experienced work rewards associated with the
      improvement in the prisoners' oral health (instrumentality). Finally, the
      dentists experienced a feeling of personal worth and a sense of commitment to
      providing care to Scottish prisoners (valence). CONCLUSIONS: The dentists'
      motivation to work in Scottish prisons may be explained by Vroom's Expectancy
      Theory. The dentists' motivation is characterised by their beliefs that their
      work will improve clinical outcomes which will be rewarded by the satisfaction
      experienced when they overcome environmental obstacles and provide oral health
      care for their prisoner-patients.

PMID- 21869769
TI  - Evaluation of workplace based assessment tools in dental foundation training.
AB  - OBJECTIVE: The aims of this survey were to evaluate the effectiveness of
      workplace based assessments (WPAs) in dental foundation training (formerly
      vocational training [VT]). METHODS: Two online questionnaire surveys were sent to
      53 foundation dental practitioners (FDPs) and their 51 trainers in the Mersey
      Deanery at month four and month nine of the one year of dental foundation
      training. The questionnaires investigated the effectiveness of and trainers' and
      trainees' satisfaction with the WPAs used in foundation training, namely dental
      evaluation of performance (D-EPs), case-based discussions (DcBD) and patients'
      assessment questionnaires (PAQs). The questionnaires also investigated the
      perceived impact of reflection and feedback associated with WPAs on clinical
      practise and improving patient care. RESULTS: A total of 41 (7.4%) FDPs and 44
      (86.3%) trainers responded. Of the 41 FDPs, the majority found that feedback from
      WPAs had a positive effect on their training, giving them insight into their
      development needs. Overall 84.1% of the FDPs felt the WPAs helped them improve
      patient care and 82.5% of trainers agreed with that outcome. CONCLUSIONS: The
      findings from this study demonstrate the value of WPAs in dental foundation
      training by the use of feedback and reflection in directing the learning of
      foundation dental practitioners and that this can lead to improved clinical
      practise and patient care.

PMID- 21869770
TI  - Survival analysis of composite Dahl restorations provided to manage localised
      anterior tooth wear (ten year follow-up).
AB  - OBJECTIVE: To evaluate ten-year survival and clinical performance of resin-based
      composite restorations placed at increased vertical dimension as a 'Dahl' type
      appliance to manage localised anterior tooth wear.Design A prospective survival
      analysis of restorations provided at a single centre.Setting UK NHS hospital and
      postgraduate institute. METHODS: The clinical performance of 283 composite resin
      restorations on 26 patients with localised anterior tooth wear was reviewed after
      a ten year follow-up period. The study used modified United States Public Health
      Service (USPHS) criteria for assessing the restorations. Survival of the
      restorations was analysed using Kaplan-Meier survival curves, the log-rank test,
      and the Cox proportional hazards regression analysis. RESULTS: The results
      indicated that the median survival time for composite resin restorations was 5.8
      years and 4.75 years for replacement restorations when all types of failure were
      considered. The restorations commonly failed as a result of wear, fracture and
      marginal discoloration. The factors that significantly influenced the survival of
      these restorations were the incisal relationship, aetiology, material used, and
      the nature of opposing dentition. The biological complications associated with
      this treatment regime were rare. Patient satisfaction remained high despite the
      long term deterioration of the restorations. CONCLUSION: With some degree of
      maintenance, repeated use of composite resin restorations to treat localised
      anterior tooth wear at an increased occlusal vertical dimension is a viable
      treatment option over a ten-year period.

PMID- 21869771
TI  - Lessons from a Greek roadmap.

PMID- 21869772
TI  - Honouring traditions.

PMID- 21869773
TI  - Our duty.

PMID- 21869774
TI  - Forgotten medical role.

PMID- 21869775
TI  - Readily achievable.

PMID- 21869776
TI  - Misleading illustration.

PMID- 21869777
TI  - Heartfelt thanks.

PMID- 21869778
TI  - Evidenced by experience.

PMID- 21869779
TI  - Storage media.

PMID- 21869780
TI  - Resource launched to support EEA qualified practitioners.

PMID- 21869781
TI  - Gene links skull and teeth abnormalities.

PMID- 21869782
TI  - No smoking day a success for the DDS.

PMID- 21869783
TI  - New scheme offers finance to go green.

PMID- 21869784
TI  - Wigan dentist completes iron man challenge.

PMID- 21869785
TI  - Speak up on CPD.

PMID- 21869789
TI  - A joint approach to treating dental phobia: a re-evaluation of a collaboration
      between community dental services and specialist psychotherapy services ten years
      on.
AB  - OBJECTIVE: To audit the records of a group of patients who had previously
      benefited from cognitive behavioural therapy (CBT) for dental phobia. AIM: To
      ascertain if they had returned to the use of intravenous (IV) sedation to
      facilitate dental treatment. Ten years ago these patients were routinely
      requiring IV sedation to facilitate dental treatment due to severe dental phobia.
      METHOD: Sixty patients entered the original pilot project. Of those, 30 were
      offered CBT and 21 attended. Twenty of those patients (95.2%) were subsequently
      able to have dental treatment without IV sedation. In this follow-up study the
      electronic records of 19 of the 20 patients who had originally been successful
      with CBT were re-audited. Our purpose was to see if there was any record of
      subsequent IV sedation administration in the intervening ten years. RESULTS: Of
      the 19 successful CBT patients available to follow-up, 100% had not received IV
      sedation since the study ten years ago. This may suggest the initial benefit of
      CBT has endured over the ten-year period. CONCLUSION: This study indicates that
      the use of CBT for patients with dental phobia proves beneficial not only in the
      initial treatment but that the benefits may endure over time. This results in a
      significant reduction in health risks to the patient from repeated IV sedation.
      It may also translate into significant financial savings for dental care
      providers. Our evidence for CBT as treatment for dental phobia suggests dental
      services should be implementing this approach now rather than pursuing further
      research.

PMID- 21869790
TI  - Microbial contamination of removable prosthodontic appliances from laboratories
      and impact of clinical storage.
AB  - Decontamination of dental instruments has recently been the subject of
      considerable debate. However, little information is available on the potential
      bacterial colonisation of dental appliances returning from dental laboratories
      and their need for decontamination. This study investigated the extent and nature
      of microbial contamination of removable prosthodontic appliances produced at
      different dental laboratories and stored in two clinical teaching units (CTU 1
      and CTU 2) of a dental hospital and school. Forty consecutive dental
      prosthodontic appliances that were being stored under varying conditions in the
      two clinical teaching units were selected for study; the appliances having been
      produced 'in-house' (hospital laboratory) or 'out-of-house' (external commercial
      laboratory). Two appliances, that were known to have undergone decontamination
      before storage, were used as controls. Swabs were taken according to a standard
      protocol and transferred to the microbiological laboratory with bacterial growth
      expressed as colony forming units (cfu) per cm(2). Microbial sampling yielded
      growth from 23 (58%) of the 40 appliances studied (CTU 1, n = 22; CTU 2, n = 18),
      with 38% of these having a high level of contamination (>42,000 cfu/cm(2)). The
      predominant bacteria isolated were Bacillus spp. (57%), pseudomonads (22%) and
      staphylococci (13%). Fungi of the genus Candida were detected in 38% of the
      samples. There was no significant difference in contamination of the appliances
      in relation to either their place of production or the CTU (p >0.05). However,
      the level of contamination was significantly higher (p = 0.035) for those
      appliances stored in plastic bag with fluid (n = 16) compared to those stored on
      models (n = 19). No growth was recovered from the two appliances that had
      undergone decontamination before storage. The research showed that appliances
      received from laboratories are often contaminated and therefore there is a need
      for routine disinfection of such items before use and a review of storage
      conditions required.

PMID- 21869791
TI  - The impact of digital image processing artefacts mimicking pathological features
      associated with restorations.
AB  - BACKGROUND: Image processing of digital X-ray images is known to have the
      potential to produce artefacts that may mimic pathology. A study was conducted at
      a UK dental radiology conference to demonstrate this effect in dentistry. METHOD:
      Sixteen digital X-rays of single teeth containing restorations were randomly
      presented in both unprocessed and processed formats to an auditorium of 42
      participants. Participants interactively scored each image on a scale from 1-5
      where 1 was definitely no pathology and 5 was definitely pathology. The display
      conditions were confirmed for each participant using a validated threshold
      contrast test. RESULTS: The results show that 52% (81/157) of responses at level
      1 for the unprocessed images changed to levels 4 or 5 after image processing.
      CONCLUSION: This study illustrates the potential for image processing artefacts
      to mimic pathology particularly at high contrast boundaries and introduces the
      risk of unnecessary interventions. In order to minimise this risk, it is
      recommended that for digital radiographs containing pathology relating to high
      contrast boundaries, non-related high contrast features such as unrelated
      restorations or tooth/bone margins are also considered to exclude the possibility
      of artefact. If there is doubt, reference should be made to the unprocessed data.

PMID- 21869792
TI  - Costs of a limited patient notification exercise following infection control
      failures in a dental surgery.
AB  - In February 2008, a primary care trust in Cheshire Merseyside was notified of
      failures in the infection control practises of a dentist working in a large group
      practice. On advice from national experts, a look-back was undertaken to identify
      any patients infected with hepatitis followed by a notification exercise of
      patients who had received invasive treatment immediately afterwards. One patient
      with hepatitis C (HCV) was identified. Sixty patients were notified by letter and
      offered advice and HCV screening. The total cost of the patient notification
      exercise (PNE) was estimated at L85,936, equating to L1,562.47 per patient who
      responded to the notification (55), or L2,455.31 per patient screened (35). All
      results were negative. While this adds to evidence that the risk to patients in
      such incidents is small, failing to investigate the possibility that BBV
      transmission has occurred would carry public health, reputational and legal
      risks. Conducting a PNE in the first instance for those patients at highest risk,
      with the option of extending it if evidence of patient-to-patient transmission is
      found, ensures that the total costs of dealing appropriately with such incidents 
      while still substantial - are at least kept to a minimum.

PMID- 21869797
TI  - Summary of: what motivates dentists to work in prisons? A qualitative
      exploration.
AB  - OBJECTIVE: To explore what motivates dentists to work in prisons using Vroom's
      theoretical model of motivation as an explanatory framework. METHOD: In-depth
      interviews were conducted with ten of the 15 dentists working in Scottish
      prisons. The focus was to explore their motivations to work in Scottish prisons.
      The data were analysed using a thematic framework based on the three motivational
      dimensions of expectancy, instrumentality and valence. RESULTS: The dentists had
      the skills to help improve their prisoner-patients' oral health but their efforts
      were often hindered by institutional rationing and the requirement to fit in with
      prison routines and procedures (expectancy). Despite these institutional
      difficulties the dentists experienced work rewards associated with the
      improvement in the prisoners' oral health (instrumentality). Finally, the
      dentists experienced a feeling of personal worth and a sense of commitment to
      providing care to Scottish prisoners (valence). CONCLUSIONS: The dentists'
      motivation to work in Scottish prisons may be explained by Vroom's Expectancy
      Theory. The dentists' motivation is characterised by their beliefs that their
      work will improve clinical outcomes which will be rewarded by the satisfaction
      experienced when they overcome environmental obstacles and provide oral health
      care for their prisoner-patients.

PMID- 21869798
TI  - Summary of: evaluation of workplace based assessment tools in foundation dental
      training.
AB  - OBJECTIVE: The aims of this survey were to evaluate the effectiveness of
      workplace based assessments (WPAs) in dental foundation training (formerly
      vocational training [VT]). METHODS: Two online questionnaire surveys were sent to
      53 foundation dental practitioners (FDPs) and their 51 trainers in the Mersey
      Deanery at month four and month nine of the one year of dental foundation
      training. The questionnaires investigated the effectiveness of and trainers' and
      trainees' satisfaction with the WPAs used in foundation training, namely dental
      evaluation of performance (D-EPs), case-based discussions (DcBD) and patients'
      assessment questionnaires (PAQs). The questionnaires also investigated the
      perceived impact of reflection and feedback associated with WPAs on clinical
      practise and improving patient care. RESULTS: A total of 41 (7.4%) FDPs and 44
      (86.3%) trainers responded. Of the 41 FDPs, the majority found that feedback from
      WPAs had a positive effect on their training, giving them insight into their
      development needs. Overall 84.1% of the FDPs felt the WPAs helped them improve
      patient care and 82.5% of trainers agreed with that outcome. CONCLUSIONS: The
      findings from this study demonstrate the value of WPAs in dental foundation
      training by the use of feedback and reflection in directing the learning of
      foundation dental practitioners and that this can lead to improved clinical
      practise and patient care.

PMID- 21869815
TI  - The gut microbiota: challenging immunology.
AB  - For several decades the intestinal microbiota was mainly studied by those
      investigating infections and diseases associated with gut health, usually from a
      microbiology point of view. In the past few years, however, it has become
      apparent that the intestinal microbiota has widespread implications in the field
      of immunology, and researchers are being compelled to explain how the microbiota
      contributes to and/or affects their studies.

PMID- 21869817
TI  - Yan, an ETS-domain transcription factor, negatively modulates the Wingless
      pathway in the Drosophila eye.
AB  - We report the identification of yan, an ETS-domain transcription factor belonging
      to the Drosophila epidermal growth factor receptor (DER) pathway, as an
      antagonist of the Wingless signalling pathway. We demonstrate that cells lacking
      yan function in the Drosophila eye show increased Wingless pathway activity, and
      inhibition of Wingless signalling in yan(-/-) cells rescues the yan mutant
      phenotype. Biochemical analysis shows that Yan physically associates with
      Armadillo, a crucial effector of the Wingless pathway, thereby suggesting a
      direct regulatory mechanism. We conclude that yan represents a new and
      unsuspected molecular link between the Wingless and DER pathways.

PMID- 21869818
TI  - Independent localization of MAP2, CaMKIIalpha and beta-actin RNAs in low copy
      numbers.
AB  - Messenger RNA localization involves the assembly of ribonucleoprotein particles
      (RNPs) and their subsequent transport along the cytoskeleton to their final
      destination. Here, we provide new evidence that microtubule-associated protein 2
      (MAP2), calcium/calmodulin-dependent protein kinase II (CaMKIIalpha) and beta
      actin RNAs localize to dendrites in distinct RNPs, which contain--unexpectedly-
      very few RNA molecules. The number of MAP2 molecules per particle is affected by
      synaptic activity and Staufen 2, indicating that RNP composition is tightly
      controlled. Our data suggest that the independent localization of individual RNAs
      in low copy numbers could contribute to tighter temporal and spatial control of
      expression in neurons and synapse-specific plasticity.

PMID- 21869819
TI  - Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704
      nanospheres.
AB  - The lung is one target organ to which solid tumors frequently metastasize. Given
      the systemic adverse effects of currently available treatments, developing
      effective strategies of drug/gene delivery directly to the lungs is therefore
      needed. Aerosol delivery is a non-invasive gene transfer approach to target the
      airways. Here, we sought to evaluate the potential to deliver a fractalkine (FKN)
      encoding plasmid formulated with the tetrafunctional amphiphilic block copolymer
      704 through aerosolization in two models of pulmonary metastases. FKN is a
      chemokine recently described as a good candidate to stimulate a strong antitumor
      immune response in various forms of cancers. Here, we have assessed the effect of
      single and repeated aerosolizations of FKN-encoding plasmid formulated with 704
      on the development of experimental lung metastases of mouse colon carcinoma and
      osteosarcoma. For this purpose, we have designed FKN-Fc sequences encoding an
      optimized version of the chemokine. Repeated intratracheal administrations of
      704/FKN-Fc markedly inhibited growth of experimental lung metastases of CT-26 and
      K7M2 cells. Our results showed that tetrafunctional amphiphilic block copolymer
      704 is a highly efficient synthetic vector for mediating local and safe gene
      transfer into the lung. In addition, FKN-Fc gene therapy of pulmonary nodules may
      provide a promising immunotherapeutic approach.

PMID- 21869816
TI  - NK cell development, homeostasis and function: parallels with CD8+ T cells.
AB  - Natural killer (NK) cells survey host tissues for signs of infection,
      transformation or stress and, true to their name, kill target cells that have
      become useless or are detrimental to the host. For decades, NK cells have been
      classified as a component of the innate immune system. However, accumulating
      evidence in mice and humans suggests that, like the B and T cells of the adaptive
      immune system, NK cells are educated during development, possess antigen-specific
      receptors, undergo clonal expansion during infection and generate long-lived
      memory cells. In this Review, we highlight the many stages that an NK cell
      progresses through during its remarkable lifetime, discussing similarities and
      differences with its close relative, the cytotoxic CD8(+) T cell.

PMID- 21869820
TI  - Virotherapy induces massive infiltration of neutrophils in a subset of tumors
      defined by a strong endogenous interferon response activity.
AB  - Oncolytic virotherapy has shown substantial promises as an alternative
      therapeutic modality for solid tumors in both preclinical studies and clinical
      trials. The main therapeutic activity of virotherapy derives from the direct
      lytic effect associated with virus replication and the induction of host immune
      responses to the infected tumor cells. In this study, we show that some human and
      murine tumor cell lines are highly resistant to the lytic effect of a type II
      herpes simplex virus-derived oncolytic virus, FusOn-H2, which was constructed by
      deleting the N-terminal region of the ICP10 gene. However, these tumor cells
      still respond exceptionally well to FusOn-H2 virotherapy in vivo. Histological
      examination of the treated tumors revealed that, in contrast to tumors supporting
      FusOn-H2 replication, implants of these highly resistant lines showed massive
      infiltration of neutrophils after virotherapy. Further analysis indicated a
      correlation between an intrinsically strong interferon response activity and the
      recruitment of neutrophils in these tumors. These results suggest that an innate
      immune response mainly represented by neutrophils in these tumors may be part of
      the virotherapy-mediated antitumor mechanism.

PMID- 21869821
TI  - Therapeutic targeting of subdural medulloblastomas using human neural stem cells
      expressing carboxylesterase.
AB  - The prognosis of medulloblastoma has improved significantly because of advances
      in multi-modal treatments; however, metastasis remains one of the prognostic
      factors for a poor outcome and is usually associated with tumor recurrence. We
      evaluated the migratory potential and therapeutic efficacy of genetically
      engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the
      subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized
      human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently
      converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN
      38). To simulate clinical metastatic medulloblastomas, we implanted human
      medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs
      (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo
      imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural
      medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE
      cells migrated to the subdural medulloblastoma site and a small number of F3.rCE
      cells were found in the lungs, pancreas, kidney and liver. Animals that received
      F3.rCE cells in combination with prodrug CPT-11 survived significantly longer
      (median survival: 142 days) than control mice that received F3.rCE cells only
      (median survival: 80 days, P<0.001) or CPT-11 only (median survival: 118 days,
      P<0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural
      medulloblastomas and demonstrate therapeutic efficacy. Our study provides data
      that supports further investigation of stem-cell-based gene therapy against
      metastatic medulloblastomas.

PMID- 21869823
TI  - EphrinA1 inhibits malignant mesothelioma tumor growth via let-7 microRNA-mediated
      repression of the RAS oncogene.
AB  - EphrinA1 binding with receptor EphA2 suppresses malignant mesothelioma (MM)
      growth. The mechanisms whereby EphrinA1 attenuates the MM cell (MMC) growth are
      not clear. In this study, we report that the activation of MMCs with EphrinA1
      leads to an induction of let-7 microRNA (miRNA) expression, repression of RAS
      proto-oncogene and the attenuation of MM tumor growth. The expression of miRNAs
      was determined by reverse transcription-quantitative polymerase chain reaction
      and in situ hybridization. RAS expression was determined by q-PCR, western
      blotting and immunofluorescence. MMC proliferation and tumor growth were
      determined by WST-1 and Matrigel assay, respectively. EphrinA1 activation induced
      several fold increases in let-7a1, let-7a3, let-7f1 and let-7f2 miRNA expression
      in MMCs. In contrast, EphrinA1 activation significantly downregulated H-RAS, K
      RAS and N-RAS expression and inhibited MMC proliferation and tumor growth. In
      MMCs transfected with 2'-O-methyl antisense oligonucleotides to let-7 miRNA,
      EphrinA1 activation failed to inhibit the proliferative response and tumor
      growth. In mismatch antisense oligonucleotide-treated MMCs, the proliferation and
      tumor growth were comparable to untreated proliferating cells. Furthermore, the
      transfection of MMCs with let-7a miRNA precursor inhibited RAS expression and
      attenuated MMC tumor growth. Our data revealed that EphrinA1 signaling induces
      let-7 miRNA expression and attenuates MM tumor growth by targeting RAS proto
      oncogene in MMCs.

PMID- 21869822
TI  - Neoadjuvant in situ gene-mediated cytotoxic immunotherapy improves postoperative
      outcomes in novel syngeneic esophageal carcinoma models.
AB  - Esophageal carcinoma is the most rapidly increasing tumor in the United States
      and has a dismal 15% 5-year survival. Immunotherapy has been proposed to improve
      patient outcomes; however, no immunocompetent esophageal carcinoma model exists
      to date to test this approach. We developed two mouse models of esophageal cancer
      by inoculating immunocompetent mice with syngeneic esophageal cell lines
      transformed by cyclin-D1 or mutant HRAS(G12V) and loss of p53. Similar to humans,
      surgery and adjuvant chemotherapy (cisplatin and 5-fluorouracil) demonstrated
      limited efficacy. Gene-mediated cyototoxic immunotherapy (adenoviral vector
      carrying the herpes simplex virus thymidine kinase gene in combination with the
      prodrug ganciclovir; AdV-tk/GCV) demonstrated high levels of in vitro
      transduction and efficacy. Using in vivo syngeneic esophageal carcinoma models,
      combining surgery, chemotherapy and AdV-tk/GCV improved survival (P=0.007) and
      decreased disease recurrence (P<0.001). Mechanistic studies suggested that AdV
      tk/GCV mediated a direct cytotoxic effect and an increased intra-tumoral
      trafficking of CD8 T cells (8.15% vs 14.89%, P=0.02). These data provide the
      first preclinical evidence that augmenting standard of care with immunotherapy
      may improve outcomes in the management of esophageal carcinoma.

PMID- 21869824
TI  - Inhibition and promotion of tumor growth with adeno-associated virus
      carcinoembryonic antigen vaccine and Toll-like receptor agonists.
AB  - Carcinoembryonic antigen (CEA) is a cancer vaccines' target. Several features of
      recombinant adeno-associated virus (rAAV) are attractive for vaccine
      applications. Combining other viral vector vaccines with Toll-like receptor (TLR)
      agonists enhances antitumor immunity. Wild-type and CEA transgenic (Tg) mice were
      immunized with rAAV-expressing CEA, the TLR9 agonist, oligodinucleotide (ODN)1826
      and the TLR7 agonist, imiquimod. Mice were challenged with MC38 colon tumor cells
      and MC38 cells expressing CEA. rAAV-CEA immunization combined with ODN1826 or
      imiquimod enhanced CEA-specific T-helper 1 immunity and protected against tumor
      challenge in wild-type but not in CEA-Tg mice. In contrast, immunization with
      rAAV-CEA in CEA-Tg mice could abrogate the antitumor effects of ODN1826 and
      promote tumor growth. Compared to wild-type, CEA-Tg mice were characterized by a
      greater myeloid suppressor cell and T-helper 2 response to TLR agonists and to
      syngeneic tumors. Depleting PDCA1(+) plasmacytoid dendritic cells and Gr1(+)
      myeloid cells increased anti-CEA immune responses in CEA-Tg mice to rAAV-CEA
      ODN1826 immunization, whereas depleting CD25(+) T cells did not. There are
      differences in the response of wild-type and CEA-Tg mice to rAAV-CEA, TLR
      agonists and syngeneic tumor. In CEA-Tg mice, tumor growth can be promoted with
      rAAV-CEA and TLR agonists. Dendritic and myeloid cells play a regulatory role.

PMID- 21869825
TI  - SV40 T/t-common polypeptide inhibits angiogenesis and growth of HER2
      overexpressing human ovarian cancer.
AB  - Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in
      human ovarian cancers and its overexpression is associated with increased
      angiogenesis, increased metastasis and reduced survival. Inhibition of HER2 in
      HER2-overexpressing cancers can lead to reduced angiogenesis and improved
      survival. Previously, we reported that SV40 T/t-common polypeptide has
      transcriptional repression activity and can inhibit HER2 expression. In this
      study, we investigated the effect of T/t-common on the angiogenesis-inducing
      activity of HER2-overexpressing human SK-OV-3 ovarian cancer cells. We found that
      compared to conditioned medium from control SK-OV-3 cancer cells, conditioned
      medium from T/t-common-expressing SK-OV-3 cells had a reduced ability to induce
      endothelial cell migration and tube formation in vitro and microvessel formation
      in vivo. These data indicate that T/t-common can inhibit the ability of SK-OV-3
      cancer cells to induce angiogenesis. T/t-common was found to be able to
      downregulate the expression of several proangiogenic factors, including vascular
      endothelial growth factor-A, interleukin-8, basic fibroblast growth factor,
      matrix metalloproteinase-2 and urokinase-type plasminogen activator, and
      upregulate antiangiogenic factors, including thrombospondin-1 and tissue
      inhibitor of metalloproteinases-1 in SK-OV-3 cancer cells. Finally, we
      demonstrated that T/t-common could inhibit the angiogenesis and growth of HER2
      overexpressing human ovarian tumor in NOD/SCID mice. Taken together, the data
      suggest that T/t-common had the potential to be developed as a new antiangiogenic
      agent specific for treating HER2-overexpressing ovarian cancers.

PMID- 21869826
TI  - Unrepairable DNA double-strand breaks initiate cytotoxicity with HSV
      TK/ganciclovir.
AB  - The herpes simplex virus thymidine kinase (HSV-TK) is the most widely used
      suicide gene in cancer gene therapy due to its superior anticancer activity with
      ganciclovir (GCV) compared with other HSV-TK substrates, such as 1-beta-D
      arabinofuranosyl thymine (araT). We have evaluated the role of DNA damage as a
      mechanism for the superiority of GCV. Using gamma-H2AX foci as an indicator of
      DNA damage, GCV induced >= sevenfold more foci than araT at similar cytotoxic
      concentrations. The number of foci decreased after removal of either drug,
      followed by an increase in Rad51 foci indicating that homologous recombination
      repair (HRR) was used to repair this damage. Notably, only GCV produced a late
      and persistent increase in gamma-H2AX foci demonstrating the induction of
      unrepairable DNA damage. Both drugs induced the ATR damage response pathway, as
      evidenced by Chk1 activation. However, GCV resulted in greater activation of ATM,
      which coincided with the late induction of gamma-H2AX foci, demonstrating the
      presence of DNA double-strand breaks (DSBs). The increase in DSBs after Rad51
      induction suggested that they occurred as a result of a failed attempt at HRR.
      These data demonstrate that the late and unrepairable DSBs observed uniquely with
      GCV account for its superior cytotoxicity and further suggest that inhibition of
      HRR will enhance cytotoxicity with HSV-TK/GCV.

PMID- 21869828
TI  - International EMBO Molecular Medicine Workshop 2011 on 'Cell Death and Disease'.

PMID- 21869827
TI  - The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and
      SMAC/Diablo.
AB  - ARTS (Sept4_i2) is a pro-apoptotic tumor suppressor protein that functions as an
      antagonist of X-linked IAP (XIAP) to promote apoptosis. It is generally thought
      that mitochondrial outer membrane permeabilization (MOMP) occurs before
      activation of caspases and is required for it. Here, we show that ARTS initiates
      caspase activation upstream of MOMP. In living cells, ARTS is localized to the
      mitochondrial outer membrane. In response to apoptotic signals, ARTS translocates
      rapidly to the cytosol in a caspase-independent manner, where it binds XIAP and
      promotes caspase activation. This translocation precedes the release of
      cytochrome C and SMAC/Diablo, and ARTS function is required for the normal timing
      of MOMP. We also show that ARTS-induced caspase activation leads to cleavage of
      the pro-apoptotic Bcl-2 family protein Bid, known to promote MOMP. We propose
      that translocation of ARTS initiates a first wave of caspase activation that can
      promote MOMP. This leads to the subsequent release of additional mitochondrial
      factors, including cytochrome C and SMAC/Diablo, which then amplifies the caspase
      cascade and causes apoptosis.

PMID- 21869829
TI  - L-selectin and SDF-1 enhance the migration of mouse and human cardiac
      mesoangioblasts.
AB  - Efficient delivery of stem cells to heart regions is still a major problem for
      cell therapy. Here, we report experiments aimed to improve migration of mouse and
      human cardiac mesoangioblasts to the damaged heart. Cardiac mesoangioblasts were
      induced to transmigrate through the endothelium by factors released by
      cardiomyocytes or cytokines, among which stromal-derived factor 1 (SDF-1) was the
      most potent. Cardiac mesoangioblasts were also delivered into the left
      ventricular (LV) chamber of mice after coronary artery ligation (CAL), and their
      in vivo homing to the damaged heart was found to be quite modest. Pretreatment of
      cardiac mesoangioblasts with SDF-1 or transient expression of L-selectin induced
      a two- to three-fold increase in their transmigration and homing to the damaged
      heart. Therefore, combined pretreatment with SDF-1 and L-selectin generated
      modified cardiac mesoangioblasts, 50% of which, after injection into the LV
      chamber of mice early after CAL, home directly to the damaged free wall of the
      heart. Finally, modified mouse cardiac mesoangioblasts, injected into the LV
      chamber regenerate a larger surface of the ventricle in long-term experiments in
      comparison with their control counterparts. This study defines the requirements
      for efficient homing of cardiac mesoangioblasts to the damaged heart and offers a
      new potent tool to optimize efficiency of future cell therapy protocols for
      cardiovascular diseases.

PMID- 21869831
TI  - Notch1 signaling regulates chondrogenic lineage determination through Sox9
      activation.
AB  - Notch signaling is involved in several cell lineage determination processes
      during embryonic development. Recently, we have shown that Sox9 is most likely a
      primary target gene of Notch1 signaling in embryonic stem cells (ESCs). By using
      our in vitro differentiation protocol for chondrogenesis from ESCs through
      embryoid bodies (EBs) together with our tamoxifen-inducible system to activate
      Notch1, we analyzed the function of Notch signaling and its induction of Sox9
      during EB differentiation towards the chondrogenic lineage. Temporary activation
      of Notch1 during early stages of EB, when lineage determination occurs, was
      accompanied by rapid and transient Sox9 upregulation and resulted in induction of
      chondrogenic differentiation during later stages of EB cultivation. Using siRNA
      targeting Sox9, we knocked down and adjusted this early Notch1-induced Sox9
      expression peak to non-induced levels, which led to reversion of Notch1-induced
      chondrogenic differentiation. In contrast, continuous Notch1 activation during EB
      cultivation resulted in complete inhibition of chondrogenic differentiation.
      Furthermore, a reduction and delay of cardiac differentiation observed in EBs
      after early Notch1 activation was not reversed by siRNA-mediated Sox9 knockdown.
      Our data indicate that Notch1 signaling has an important role during early stages
      of chondrogenic lineage determination by regulation of Sox9 expression.

PMID- 21869830
TI  - Hypoxia-inducible factor-2alpha regulates Fas-mediated chondrocyte apoptosis
      during osteoarthritic cartilage destruction.
AB  - Apoptosis of articular chondrocytes is associated with the pathogenesis of
      osteoarthritis (OA). Recently, we demonstrated that hypoxia-inducible factor
      (HIF)-2alpha, encoded by Epas1, causes OA cartilage destruction by regulating the
      expression of various matrix-degrading enzymes. Here, we investigated the
      involvement of HIF-2alpha in chondrocyte apoptosis and OA cartilage destruction.
      HIF-2alpha levels in human and mouse OA chondrocytes were markedly elevated in
      association with increased apoptosis of articular chondrocytes. Overexpression or
      knockdown of HIF-2alpha alone did not cause chondrocyte apoptosis. However, HIF
      2alpha expression markedly increased chondrocyte apoptosis in the presence of an
      agonistic anti-Fas (CD95) antibody. HIF-2alpha enhanced Fas expression and
      potentiated downstream signaling pathways, increasing the activity of initiator
      and executioner caspases. Overexpression of HIF-2alpha in mouse cartilage tissue,
      either by intra-articular injection of Epas1 adenovirus (Ad-Epas1) or in the
      context of chondrocyte-specific Epas1 transgenic mice, increased chondrocyte
      apoptosis and cartilage destruction. In contrast, chondrocyte-specific knockout
      of Epas1 in mice suppressed DMM (destabilization of the medial meniscus)-induced
      chondrocyte apoptosis and inhibited OA cartilage destruction. Moreover, Fas
      deficient mice exhibited diminished chondrocyte apoptosis and OA cartilage
      destruction in response to Ad-Epas1 injection or DMM surgery. Taken together, our
      results demonstrate that HIF-2alpha potentiates Fas-mediated chondrocyte
      apoptosis, which is associated with OA cartilage destruction.

PMID- 21869832
TI  - Surgical treatment of necrotic scleral calcification using combined conjunctival
      autografting and an amniotic membrane inlay filling technique.
AB  - PURPOSE: To introduce a novel technique to treat necrotic scleral calcification
      caused by previous regional conjunctivectomy using conjunctival autografting and
      amniotic membrane inlay filling, and to evaluate the clinical outcome. METHODS:
      Ten patients (11 eyes, 12 regions) who had undergone regional conjunctivectomy
      with postoperative mitomycin C (MMC) for pterygia or pingueculae were included.
      Scleral calcification was removed using a bevel-down crescent knife. After the
      conjunctival donor tissue was harvested from the upper bulbar conjunctiva, the
      tissue was grafted to the scleral defect and secured with sutures. Amniotic
      membrane was inserted randomly into spaces between the conjunctival graft and the
      scleral bed. Protective amniotic membrane was transplanted over the graft, with
      stromal side up. RESULTS: Scleral calcification developed in ischaemic areas in
      11 of the 12 regions; 50% of cases had a surface defect seen with a fluorescent
      dye. The grafted conjunctiva epithelialized successfully in all cases. In 10
      regions, the epithelialization occurred in 1 or 2 weeks. In the remaining two
      regions, one region required another surgery because of graft failure, and
      epithelialization occurred in the last region in 9 weeks. Vascular growth into
      the graft from the surrounding tissue occurred in all cases in 1 to 10 weeks. The
      surgical wound stabilized 3 weeks postoperatively. CONCLUSION: The combined
      technique had high success rates of graft survival and good revitalization of the
      necrotic area of scleral calcification, eliminated the need for invasive and time
      consuming scleral autografting or allografting, and provided good cosmesis.
      Scleral ischaemia, which was caused by MMC, may induce scleral calcification.

PMID- 21869833
TI  - A co-twin study of the relative effect of birth weight and gestational age on
      retinopathy of prematurity.
AB  - PURPOSE: To determine the relative effect of birth weight and gestational age on
      retinopathy of prematurity (ROP) using preterm twin pairs discordant for birth
      weight. METHODS: This study was a retrospective cohort study including 55
      consecutive twin pairs of 110 preterm infants (gestational age <=33 weeks). The
      outcomes of ROP including occurrence (any stage), severe ROP (stage 3 or more),
      and clinically significant ROP requiring laser treatment were compared between
      twins with the lower birth weight from each pair and their co-twins with the
      higher birth weight. Using twin pairs having different birth weight and identical
      gestational age, the independent effects of prematurity and intrauterine growth
      on ROP could be evaluated. Other perinatal morbidities related to prematurity
      were also compared between twin pairs. RESULTS: No significant differences in ROP
      between larger and smaller infants were observed in the twin-paired analysis
      while analysis on individual infants showed strong association between small
      birth weight and ROP outcomes. However, in both the larger and smaller infant
      groups, gestational age of <28 weeks was significantly associated with ROP
      outcomes. No differences were found between twin pairs regarding other perinatal
      morbidities including bronchopulmonary dysplasia, respiratory distress syndrome,
      patent ductus arteriosus, intraventricular hemorrhage, and periventricular
      leukomalacia. CONCLUSIONS: Birth weight is not associated with ROP, while
      gestational age is in the twin-paired study, suggesting that gestational age is a
      better predictor of ROP than birth weight. This indicates that maturity is more
      important in the pathogenesis of ROP than intrauterine growth.

PMID- 21869834
TI  - Revalidation and electronic cataract surgery audit: a Scottish survey on current
      practice and opinion.
AB  - PURPOSE: To determine current knowledge and opinion on revalidation, and methods
      of cataract surgery audit in Scotland and to outline the current and future
      possibilities for electronic cataract surgery audit. METHODS: In 2010 we
      conducted a prospective, cross-sectional, Scottish-wide survey on revalidation
      knowledge and opinion, and cataract audit practice among all senior NHS
      ophthalmologists. Results were anonymised and recorded manually for analysis.
      RESULTS: In all, 61% of the ophthalmologists surveyed took part. Only 33% felt
      ready to take part in revalidation, whereas 76% felt they did not have adequate
      information about the process. Also, 71% did not feel revalidation would improve
      patient care, but 85% agreed that cataract surgery audit is essential for
      ophthalmic practice. In addition, 91% audit their cataract outcomes; 52% do so
      continuously. Further, 63% audit their subspecialist surgical results. Only 25%
      audit their cataract surgery practice electronically, and only 12% collect
      clinical data using a hospital PAS system. Funding and system incompatibility
      were the main reasons cited for the lack of electronic audit setup. Currently,
      eight separate hospital IT patient administration systems are used across 14
      health boards in Scotland. CONCLUSION: Revalidation is set to commence in 2012.
      The Royal College of Ophthalmologists will use cataract outcome audit as a tool
      to ensure surgical competency for the process. Retrospective manual auditing of
      cataract outcome is time consuming, and can be avoided with an electronic system.
      Scottish ophthalmologists view revalidation with scepticism and appear to have
      inadequate knowledge of the process. However, they strongly agree with the
      concept of cataract surgery audit. The existing and future electronic
      applications that may support surgical audit are commercial electronic records,
      web-based applications, centrally funded software applications, and robust NHS
      connections between community and hospital.

PMID- 21869835
TI  - Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
      with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair
      analysis.
AB  - Acute myeloid leukemia (AML) with t(6;9)(p23;q34) is well known to have a poor
      prognosis treated with chemotherapy and autotransplantation. The presence of this
      karyotype is an indicator for allogeneic hematopoietic stem cell transplantation
      (HSCT); however, the impact of t(6;9)(p23;q34) on the HSCT outcome remains
      unclear. We conducted a matched-pair analysis of de novo AML patients with and
      without t(6;9)(p23;q34) using data obtained from the Japanese HSCT data registry.
      A total of 57 patients with t(6;9)(p23;q34) received transplants between 1996 and
      2007, and 171 of 2056 normal karyotype patients matched for age, disease status
      at HSCT and graft source were selected. The overall survival, disease-free
      survival, cumulative incidence of relapse and the non-relapse mortality in
      t(6;9)(p23;q34) patients were comparable to those for normal karyotype patients.
      A univariate analysis showed that t(6;9)(p23;q34) had no significant impact on
      the overall survival. These findings suggest that allogeneic HSCT may overcome
      the unfavorable impact of t(6;9)(p23;q34) as an independent prognostic factor.

PMID- 21869836
TI  - The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544)
      effectively kills primary pediatric acute lymphoblastic leukemia cells.
AB  - We investigated whether the newly developed antibody (Ab) -targeted therapy
      inotuzumab ozogamicin (CMC-544), consisting of a humanized CD22 Ab linked to
      calicheamicin, is effective in pediatric primary B-cell precursor acute
      lymphoblastic leukemia (BCP-ALL) cells in vitro, and analyzed which parameters
      determine its efficacy. CMC-544 induced dose-dependent cell kill in the majority
      of BCP-ALL cells, although IC(50) values varied substantially (median 4.8 ng/ml,
      range 0.1-1000 ng/ml at 48 h). The efficacy of CMC-544 was highly dependent on
      calicheamicin sensitivity and CD22/CMC-544 internalization capacity of BCP-ALL
      cells, but hardly on basal and renewed CD22 expression. Although CD22 expression
      was essential for uptake of CMC-544, a repetitive loop of CD22 saturation,
      CD22/CMC-544 internalization and renewed CD22 expression was not required to
      achieve intracellular threshold levels of calicheamicin sufficient for efficient
      CMC-544-induced apoptosis in BCP-ALL cells. This is in contrast to studies with
      the comparable CD33 immunotoxin gemtuzumab ozogamicin (Mylotarg) in acute myeloid
      leukemia (AML) patients, in which complete and prolonged CD33 saturation was
      required for apoptosis induction. These data suggest that CMC-544 treatment may
      result in higher response rates in ALL compared with response rates obtained in
      AML with Mylotarg, and that therefore clinical studies in ALL, preferably with
      multiple low CMC-544 dosages, are warranted.

PMID- 21869837
TI  - Commentary: does immune suppression increase risk of developing acute myeloid
      leukemia?
AB  - Risk of developing some cancers is markedly increased in settings of immune
      suppression including after solid organ transplants and in persons with inherited
      immune-deficiency disorders and those with HIV-1 infection. These cancers include
      lymphomas, melanoma and non-melanoma skin cancers, kidney and cervical cancers,
      Kaposi sarcoma and neuroblastoma. There are no reports of an increased acute
      myeloid leukemia (AML) in settings of immune suppression. This is curious because
      some data suggest the immune suppression may be important in increasing AML risk
      in experimental settings, and that immune stimulation may be useful in treating
      AML. To see whether immune suppression is correlated with an increased risk of
      developing AML, we analyzed data from 248224 recipients of kidney (N=217219) and
      heart (N=31005) transplants. Among the kidney transplant recipients, the
      standardized incidence ratio (SIR) for developing AML was 1.90 (95% confidence
      interval, 1.4-2.4; P<0.001). Among the heart transplant recipients, the SIR was
      5.1 (3.4-7.1; P<0.001). These data suggest immune suppression increases risk of
      developing AML and that this risk is even higher, following intense prolonged
      immune suppression. Implications for AML development and therapy are discussed.

PMID- 21869838
TI  - WT1 peptide vaccination following allogeneic stem cell transplantation in
      pediatric leukemic patients with high risk for relapse: successful maintenance of
      durable remission.

PMID- 21869839
TI  - (+)alpha-Tocopheryl succinate inhibits the mitochondrial respiratory chain
      complex I and is as effective as arsenic trioxide or ATRA against acute
      promyelocytic leukemia in vivo.
AB  - The vitamin E derivative (+)alpha-tocopheryl succinate (alpha-TOS) exerts pro
      apoptotic effects in a wide range of tumors and is well tolerated by normal
      tissues. Previous studies point to a mitochondrial involvement in the action
      mechanism; however, the early steps have not been fully elucidated. In a model of
      acute promyelocytic leukemia (APL) derived from hCG-PML-RARalpha transgenic mice,
      we demonstrated that alpha-TOS is as effective as arsenic trioxide or all-trans
      retinoic acid, the current gold standards of therapy. We also demonstrated that
      alpha-TOS induces an early dissipation of the mitochondrial membrane potential in
      APL cells and studies with isolated mitochondria revealed that this action may
      result from the inhibition of mitochondrial respiratory chain complex I.
      Moreover, alpha-TOS promoted accumulation of reactive oxygen species hours before
      mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo
      antileukemic action and a novel mitochondrial target were revealed for alpha-TOS,
      as well as mitochondrial respiratory complex I was highlighted as potential
      target for anticancer therapy.

PMID- 21869840
TI  - How to manage primary amyloidosis.
AB  - Immunoglobulin light chain amyloidosis is a protein deposition disorder where the
      precursor protein represents a monoclonal immunoglobulin light or heavy chain.
      Deposition in viscera results in restrictive cardiomyopathy, nephrotic range
      proteinuria, demyelinating peripheral neuropathy, hepatomegaly and malabsorption
      syndrome. Diagnosis requires biopsy with Congo red staining. Invasive biopsies
      are not required generally. It is essential that after a histologic diagnosis is
      obtained, the tissue is validated to have an immunoglobulin light chain
      composition so patients are spared unnecessary chemotherapy. The disease
      prognosis and patient monitoring are linked to serialized measurement of cardiac
      biomarkers and immunoglobulin-free light chains. Most patients require cytotoxic
      chemotherapy. For some patients, this therapy involves stem cell collection and
      myeloablative chemotherapy; for others, chemotherapy includes an alkylator and a
      corticosteroid; and for some, it involves addition of a novel agent in the form
      of an immunomodulatory drug or a proteasome inhibitor. Delays in diagnosis
      continue to be an obstacle to initiating effective therapy. Early mortality rates
      remain high. Effective chemotherapy can result in reversal of organ dysfunction
      and recovery. Reductions in light chain production translate to improved
      survival.

PMID- 21869841
TI  - NIH-defined graft-versus-host disease after reduced intensity or myeloablative
      conditioning in patients with acute myeloid leukemia.

PMID- 21869844
TI  - 1,2,3-Trichloropropane.

PMID- 21869843
TI  - Functional role of BAALC in leukemogenesis.

PMID- 21869842
TI  - ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with
      contemporary therapy.
AB  - ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute
      lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug
      sensitive leukemia are improved by contemporary risk-directed therapy, we studied
      clinical features, response and adverse events of 168 children with newly
      diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N=36),
      XIIIB (N=38) and XV (N=94). Results were compared with 494 ETV6-RUNX1-negative B
      precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre
      treatment classification as low risk and lower levels of minimal residual disease
      (MRD) on day 19 of therapy (P<0.001). Event-free survival (EFS) or overall
      survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total
      XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had
      significantly better EFS (P=0.04; 5-year estimate, 96.8+/-2.4% versus 88.3+/
      2.5%) and OS (P=0.04; 98.9+/-1.4% versus 93.7+/-1.8%) than those without ETV6
      RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor
      associated with higher OS was the treatment protocol Total XV (versus XIIIA or
      XIIIB) (P=0.01). Thus, the MRD-guided treatment schema including intensive
      asparaginase and high-dose methotrexate in the Total XV study produced
      significantly better outcomes than previous regimens and demonstrated that nearly
      all children with ETV6-RUNX1 ALL can be cured.

PMID- 21869845
TI  - High Frequency PMN-PT 1-3 Composite Transducer for Ultrasonic Imaging
      Application.
AB  - Development of PMN-PT single crystal/epoxy 1-3 composites for high-frequency
      ultrasonic transducers application is presented. The composite was fabricated by
      using a DRIE dry etching process with a 45% volume fraction of PMN-PT. A 35 MHz
      ultrasound flat transducer was fabricated with the composite, which was found to
      have an effective electromechanical coupling coefficient of 0.81, an insertion
      loss of 18 db, and a -6 dB bandwidth as high as 100%. Tungsten wire phantom image
      shows that the transducer had an axial resolution of 30 MUm, which was in good
      agreement with the theoretical expectation. The initial results showed that the
      PMN-PT/epoxy 1-3 composite has many attractive properties over conventional
      piezoelectric materials for medical imaging applications.

PMID- 21869846
TI  - Iterative PET Image Reconstruction Using Translation Invariant Wavelet Transform.
AB  - The present work describes a Bayesian maximum a posteriori (MAP) method using a
      statistical multiscale wavelet prior model. Rather than using the orthogonal
      discrete wavelet transform (DWT), this prior is built on the translation
      invariant wavelet transform (TIWT). The statistical modeling of wavelet
      coefficients relies on the generalized Gaussian distribution. Image
      reconstruction is performed in spatial domain with a fast block sequential
      iteration algorithm. We study theoretically the TIWT MAP method by analyzing the
      Hessian of the prior function to provide some insights on noise and resolution
      properties of image reconstruction. We adapt the key concept of local shift
      invariance and explore how the TIWT MAP algorithm behaves with different scales.
      It is also shown that larger support wavelet filters do not offer better
      performance in contrast recovery studies. These theoretical developments are
      confirmed through simulation studies. The results show that the proposed method
      is more attractive than other MAP methods using either the conventional Gibbs
      prior or the DWT-based wavelet prior.

PMID- 21869847
TI  - Parenthood, Childlessness, and Well-Being: A Life Course Perspective.
AB  - This article reviews recent research (1999 - 2009) on the effects of parenthood
      on wellbeing. We use a life course framework to consider how parenting and
      childlessness influence well-being throughout the adult life course. We place
      particular emphasis on social contexts and how the impact of parenthood on well
      being depends on marital status, gender, race/ethnicity, and socioeconomic
      status. We also consider how recent demographic shifts lead to new family
      arrangements that have implications for parenthood and well-being. These include
      stepparenting, parenting of grandchildren, and childlessness across the life
      course.

PMID- 21869848
TI  - Cohort Changes in the Socio-demographic Determinants of Gender Egalitarianism.
AB  - Arguments about the spread of gender egalitarian values through the population
      highlight several sources of change. First, structural arguments point to
      increases in the proportion of women with high education, jobs with good pay,
      commitment to careers outside the family, and direct interests in gender
      equality. Second, value shift arguments contend that gender norms change with
      social and economic development among women and men in diverse positions -
      traditional and non-traditional alike. Third, diffusion arguments suggest that
      structural change leads to adoption of new ideas and values supportive of gender
      equality by non-traditional and innovative groups in society, but that the new
      ideas later diffuse to other groups through cultural processes. Using the General
      Social Survey from 1977 to 2006 and comparing the determinants of gender
      egalitarianism across 86 cohorts born from roughly 1900 through 1985, multilevel
      models support the diffusion arguments.

PMID- 21869849
TI  - Biosynthesis of the Apoptolidins in Nocardiopsis sp. FU 40.
AB  - The apoptolidins are 20/21-membered macrolides produced by Nocardiopsis sp. FU40.
      Several members of this family are potent and remarkably selective inducers of
      apoptosis in cancer cell lines, likely via a distinct mitochondria associated
      target. To investigate the biosynthesis of this natural product, the complete
      genome of the apoptolidin producer Nocardiopsis sp. FU40 was sequenced and a 116
      Kb region was identified containing a putative apoptolidin biosynthetic gene
      cluster. The apoptolidin gene cluster comprises a type I polyketide synthase,
      with 13 homologating modules, apparently initiated in an unprecedented fashion
      via transfer from a methoxymalonyl-acyl carrier protein loading module. Spanning
      approximately 39 open reading frames, the gene cluster was cloned into a series
      of overlapping cosmids and functionally validated by targeted gene disruption
      experiments in the producing organism. Disruption of putative PKS and P(450)
      genes delineated the roles of these genes in apoptolidin biosynthesis and
      chemical complementation studies demonstrated intact biosynthesis peripheral to
      the disrupted genes. This work provides insight into details of the biosynthesis
      of this biologically significant natural product and provides a basis for future
      mutasynthetic methods for the generation of non-natural apopotolidins.

PMID- 21869850
TI  - On the Preparation of Enantiomerically Pure Isonitriles from Amino Acid Esters
      and Peptides.
AB  - An improved method for the synthesis of enantiomerically pure isonitriles from
      amino acid esters and dipeptides is described.

PMID- 21869851
TI  - Assessment of Indoor Route-finding Technology for People with Visual Impairment.
AB  - This study investigated navigation with route instructions generated by digital
      map software and synthetic speech. Participants, either visually impaired or
      sighted wearing blind folds, successfully located rooms in an unfamiliar
      building. Users with visual impairment demonstrated better route-finding
      performance when the technology provided distance information in number of steps
      rather than walking time or number of feet.

PMID- 21869852
TI  - The valence of sex:Automatic affective associations in erotophilia and
      erotophobia.
AB  - Sexual stimuli may elicit positive and negative emotions that can impact sexual
      thoughts, responses, and behavior. To date, most research on affect and sexuality
      has focused on conscious processes and affective states. Less is known about how
      automatic and trait-level affective processes influence our reactions to sexual
      stimuli. This study used a priming task with backward masking and a trait measure
      of erotophobia-erotophilia - the tendency to respond to sex on a negative-to
      positive continuum - to improve our understanding of the role of automatic and
      affective processes in response to sexual stimuli. Erotophilic individuals
      demonstrated automatic associations between sexual primes and positively-valenced
      targets, whereas erotophobic individuals classified negatively-valenced targets
      faster regardless of whether primes were sexual or neutral. The findings suggest
      that the valence of sexual stimuli can be processed automatically and is
      associated with trait-level affective responses to sex. Implications for research
      on risky sexual behavior and sexual dysfunction are discussed.

PMID- 21869854
TI  - Prereading Deficits in Children in Foster Care.
AB  - Reading skills are core competencies in children's readiness to learn and may be
      particularly important for children in foster care, who are at risk for academic
      difficulties and higher rates of special education placement. In this study,
      prereading skills (phonological awareness, alphabetic knowledge, and oral
      language ability) and kindergarten performance of 63 children in foster care were
      examined just prior to and during the fall of kindergarten. The children
      exhibited prereading deficits with average prereading scores that fell at the
      30(th) to 40(th) percentile. Variations in prereading skills (particularly
      phonological awareness) predicted kindergarten teacher ratings of early literacy
      skills in a multivariate path analysis. These findings highlight the need for
      interventions focused on prereading skills for children in foster care.

PMID- 21869853
TI  - Steric Crowding Makes Challenging C(sp3)-F Reductive Eliminations Feasible.
AB  - A high-yielding fluorination of (triphos)Pt-R(+) has been achieved using an array
      of F(+) sources, with XeF(2) yielding R-F in minutes. The C-F coupling proved to
      be a stereoretentive process that proceeds via a concerted reductive elimination
      from a putative dicationic Pt(IV) center. The larger the steric congestion of the
      (triphos)Pt-C(sp3) (+) complexes, the more efficient the fluorination, seemingly
      a result of sterically accelerated C-F reductive elimination along with
      simultaneous deceleration of its competing processes (beta-H elimination).

PMID- 21869856
TI  - Bi-Linear Regression for O Quantification: Modeling across the Elution Profile.
AB  - MOTIVATION: Interpreting and quantifying labeled mass-spectrometry data is
      complex and requires automated algorithms, particularly for large scale proteomic
      profiling. Here, we propose the use of bi-linear regression to quantify relative
      abundance across the elution profile in a unified model. The bi-linear regression
      model takes advantage of the fact that while peptides differ in overall abundance
      across the elution profile multiplicatively, the relative abundance between the
      mixed samples remains constant across the elution profile. We describe how to
      apply bi-linear regression models to (18)O stable-isotope labeled data, which
      allows for the direct comparison of two samples simultaneously. Interpretation of
      model parameters is also discussed. The incorporation rate of the labeling
      isotope is estimated as part of the modeling process and can be used as a measure
      of data quality. Application is demonstrated in a controlled experiment as well
      as in a complex mixture. RESULTS: Bi-linear regression models allow for more
      precise and accurate estimates of abundance, in comparison to methods that treat
      each spectrum independently, by taking into account the abundance of the molecule
      throughout the entire elution profile, with precision increased by one-to-two
      orders of magnitude.

PMID- 21869855
TI  - New Therapeutic Approaches for Waldenstrom Macroglobulinemia.
AB  - Waldenstrom Macroglobulinemia (WM) is a B-cell disorder characterized by the
      infiltration of the bone marrow (BM) with lymphoplasmacytic cells, as well as
      detection of an IgM monoclonal gammopathy in the serum. WM is an incurable
      disease, with an overall medial survival of only 5-6 years. First-line therapy of
      WM has been based on single-agent or combination therapy with alkylator agents
      (e.g. chlorambucil or cyclophasphamide), nucleoside analogues (cladribine or
      fludarabine), and the monoclonal antibody rituximab. Novel therapeutic agents
      that have demonstrated efficacy in WM include thalidomide, lenalidomide,
      bortezomib, everolimus, Atacicept, and perifosine. The range of the ORR to these
      agents is between 25-80%. Ongoing and planned future clinical trials include
      those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as
      carfilzomib, histone deacetylase inhibitors such as panobinostat, humanized CD20
      antibodies such as Ofatumumab, and additional alkylating agents such as
      bendamustine. These agents, when compared to traditional chemotherapeutic agents,
      may lead in the future to higher responses, longer remissions and better quality
      of life for patients with WM.

PMID- 21869857
TI  - Bacterial vaginosis and the natural history of human papillomavirus.
AB  - OBJECTIVE: To evaluate associations between common vaginal infections and human
      papillomavirus (HPV). STUDY DESIGN: Data from up to 15 visits on 756 HIV-infected
      women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology
      Research Study (HERS) were evaluated for associations of bacterial vaginosis,
      trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident
      HPV, and clearance of HPV in multivariate analysis. RESULTS: Bacterial vaginosis
      (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04,
      1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed
      clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the
      preceding or current visit was associated with incident HPV, in an alternate
      model for the outcome of incident BV, HPV at the current, but not preceding,
      visit was associated with incident BV. CONCLUSION: These findings underscore the
      importance of prevention and successful treatment of bacterial vaginosis.

PMID- 21869858
TI  - Nonhuman primate models used to study pelvic inflammatory disease caused by
      Chlamydia trachomatis.
AB  - Pelvic inflammatory disease (PID) is a global health concern that is associated
      with significant morbidity and is a major cause of infertility. Throughout
      history animals have been used for anatomical studies and later as models of
      human disease. In particular, nonhuman primates (NHPs) have permitted
      investigations of human disease in a biologically, physiologically, and
      anatomically similar system. The use of NHPs as human PID models has led to a
      greater understanding of the primary microorganisms that cause disease (e.g.,
      Chlamydia trachomatis and Neisseria gonorroheae), the pathogenesis of infection
      and its complications, and the treatment of people with PID. This paper explores
      historical and contemporary aspects of NHP modeling of chlamydial PID, with an
      emphasis on advantages and limitations of this approach and future directions for
      this research.

PMID- 21869859
TI  - Partition Efficiency of High-Pitch Locular Multilayer Coil for Countercurrent
      Chromatographic Separation of Proteins Using Small-Scale Cross-Axis Coil Planet
      Centrifuge and Application to Purification of Various Collagenases with Aqueous
      Aqueous Polymer Phase Systems.
AB  - Partition efficiency of the high-pitch locular multilayer coil was evaluated in
      countercurrent chromatographic (CCC) separation of proteins with an aqueous
      aqueous polymer phase system using the small-scale cross-axis coil planet
      centrifuge (X-axis CPC) fabricated in our laboratory. The separation column was
      specially made by high-pitch (ca 5 cm) winding of 1.0 mm I.D., 2.0 mm O.D.
      locular tubing compressed at 2 cm intervals with a total capacity of 29.5 mL. The
      protein separation was performed using a set of stable proteins including
      cytochrome C, myoglobin, and lysozyme with the 12.5% (w/w) polyethylene glycol
      (PEG) 1000 and 12.5% (w/w) dibasic potassium phosphate system (pH 9.2) under 1000
      rpm of column revolution. This high-pitch locular tubing yielded substantially
      increased stationary phase retention than the normal locular tubing for both
      lower and upper mobile phases. In order to demonstrate the capability of the high
      pitch locular tubing, the purification of collagenase from the crude commercial
      sample was carried out using an aqueous-aqueous polymer phase system. Using the
      16.0% (w/w) PEG 1000 - 6.3% (w/w) dibasic potassium phosphate - 6.3% (w/w)
      monobasic potassium phosphate system (pH 6.6), collagenase I, II, V and X derived
      from Clostridium hystolyticum were separated from other proteins and colored
      small molecular weight compounds present in the crude commercial sample, while
      collagenase N-2 and S-1 from Streptomyces parvulus subsp. citrinus were eluted
      with impurities at the solvent front with the upper phase. The collagenase from
      C. hystolyticum retained its enzymatic activity in the purified fractions. The
      overall results demonstrated that the high-pitch locular multilayer coil is
      effectively used for the CCC purification of bioactive compounds without loss of
      their enzymatic activities.

PMID- 21869860
TI  - Adherent primary cultures of mouse intercostal muscle fibers for isolated fiber
      studies.
AB  - Primary culture models of single adult skeletal muscle fibers dissociated from
      locomotor muscles adhered to glass coverslips are routine and allow monitoring of
      functional processes in living cultured fibers. To date, such isolated fiber
      cultures have not been established for respiratory muscles, despite the fact that
      dysfunction of core respiratory muscles leading to respiratory arrest is the most
      common cause of death in many muscular diseases. Here we present the first
      description of an adherent culture system for single adult intercostal muscle
      fibers from the adult mouse. This system allows for monitoring functional
      properties of these living muscle fibers in culture with or without electrical
      field stimulation to drive muscle fiber contraction at physiological or
      pathological respiratory firing patterns. We also provide initial
      characterization of these fibers, demonstrating several common techniques in this
      new model system in the context of the established Flexor Digitorum Brevis muscle
      primary culture model.

PMID- 21869861
TI  - Early detection of tumor response by FLT/microPET Imaging in a C26 murine colon
      carcinoma solid tumor animal model.
AB  - Fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)
      imaging demonstrated the change of glucose consumption of tumor cells, but
      problems with specificity and difficulties in early detection of tumor response
      to chemotherapy have led to the development of new PET tracers. Fluorine-18
      fluorothymidine ((18)F-FLT) images cellular proliferation by entering the salvage
      pathway of DNA synthesis. In this study, we evaluate the early response of colon
      carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal
      carcinoma-bearing mice by (18)F-FDG and (18)F-FLT. The male BALB/c mice were
      bilaterally inoculated with 1 * 10(5) and 1 * 10(6) C26 tumor cells per flank.
      Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after (18)F-FDG
      and (18)F-FLT imaging. The biodistribution of (18)F-FDG and (18)F-FLT were
      followed by the microPET imaging at day 9. For the quantitative measurement of
      microPET imaging at day 9, (18)F-FLT was superior to (18)F-FDG for early
      detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The
      data of biodistribution showed similar results with those from the quantification
      of SUV (standard uptake value) by microPET imaging. The study indicates that
      (18)F-FLT/microPET is a useful imaging modality for early detection of
      chemotherapy in the colorectal mouse model.

PMID- 21869862
TI  - The construction of chimeric T-Cell receptor with spacer base of modeling study
      of VHH and MUC1 interaction.
AB  - Adaptive cell immunotherapy with the use of chimeric receptors leads to the best
      and most specific response against tumors. Chimeric receptors consist of a
      signaling fragment, extracellular spacer, costimulating domain, and an antibody.
      Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in
      chimeric receptors. Since peptide sequences have an influence on chimeric
      receptors, the effect of peptide domains on each other's conformation were
      investigated. CD3Zeta, CD28, VHH and CD8alpha, and FcgIIalpha are used as
      signaling moieties, costimulating domain, antibody, and spacers, respectively. To
      investigate the influence of the ligation of spacers on the conformational
      structure of VHH, models of VHH were constructed. Molecular dynamics simulation
      was run to study the influence of the presence of spacers on the conformational
      changes in the binding sites of VHH. Root mean square deviation and root mean
      square fluctuation of critical segments in the binding site showed no noticeable
      differences with those in the native VHH. Results from molecular docking revealed
      that the presence of spacer FcgIIalpha causes an increasing effect on VHH with
      MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1.
      Expression analysis and evaluation of their functions were examined. The results
      showed good expression and function.

PMID- 21869863
TI  - Enteromorpha compressa exhibits potent antioxidant activity.
AB  - The green macroalgae, Enteromorpha compressa (Linnaeus) Nees, Ulva lactuca, and
      E. linza, were seasonally collected from Abu Qir bay at Alexandria (Mediterranean
      Sea) This work aimed to investigate the seasonal environmental conditions,
      controlling the green algal growth, predominance, or disappearance and
      determining antioxidant activity. The freshly collected selected alga (E.
      compressa) was subjected to pigment analysis (chlorophyll and carotenoids)
      essential oil and antioxidant enzyme determination (ascorbate oxidase and
      catalase). The air-dried ground alga was extracted with ethanol (crude extract)
      then sequentially fractionated by organic solvents of increasing polarity
      (petroleum ether, chloroform, ethyl acetate, and water). Antioxidant activity of
      all extracts was assayed using different methods (total antioxidant, DPPH [2, 2
      diphenyl-1-picrylhydrazyl], ABTS [2, 2 azino-bis ethylbenzthiazoline-6-sulfonic
      acid], and reducing power, and beta-carotene linoleic acid bleaching methods).
      The results indicated that the antioxidant activity was concentration and time
      dependent. Ethyl acetate fraction demonstrated higher antioxidant activity
      against DPPH method (82.80%) compared to the synthetic standard butylated
      hydroxyl toluene (BHT, 88.5%). However, the crude ethanolic extract, pet ether,
      chloroform fractions recorded lower to moderate antioxidant activities (49.0,
      66.0, and 78.0%, resp.). Using chromatographic and spectroscopic analyses, an
      active compound was separated and identified from the promising ethyl acetate
      fraction.

PMID- 21869864
TI  - An integrative genomics approach to biomarker discovery in breast cancer.
AB  - Genome-wide association studies (GWAS) have successfully identified genetic
      variants associated with risk for breast cancer. However, the molecular
      mechanisms through which the identified variants confer risk or influence
      phenotypic expression remains poorly understood. Here, we present a novel
      integrative genomics approach that combines GWAS information with gene expression
      data to assess the combined contribution of multiple genetic variants acting
      within genes and putative biological pathways, and to identify novel genes and
      biological pathways that could not be identified using traditional GWAS. The
      results show that genes containing SNPs associated with risk for breast cancer
      are functionally related and interact with each other in biological pathways
      relevant to breast cancer. Additionally, we identified novel genes that are co
      expressed and interact with genes containing SNPs associated with breast cancer.
      Integrative analysis combining GWAS information with gene expression data
      provides functional bridges between GWAS findings and biological pathways
      involved in breast cancer.

PMID- 21869865
TI  - Therapeutic vaccines in renal cell carcinoma.
AB  - Metastatic renal cell carcinoma (mRCC) is a lethal disease. The advent of
      tyrosine kinase inhibitors (TKIs) has changed the disease process, yet the
      majority of patients will develop treatment-resistant disease. IL-2 based
      immunotherapy in mRCC is the only US FDA-approved treatment with curative
      results. Immunotherapeutic vaccine approaches to mRCC have been under
      investigation for several decades with mixed results. The recent FDA-approval of
      the first cellular immunotherapy in prostate cancer (Provenge((r))) has
      reinvigorated the search for similar vaccines approaches in mRCC. This review
      introduces the concepts and different features required for a successful
      anticancer vaccine approach.

PMID- 21869867
TI  - Gastro-hep news.

PMID- 21869866
TI  - Beyond microscopic reversibility: Are observable non-equilibrium processes
      precisely reversible?
AB  - Although the principle of microscopic reversibility has been studied for many
      decades, there remain ambiguities in its application to non-equilibrium processes
      of importance to chemistry, physics and biology. Examples include whether protein
      unfolding should follow the same pathways and in the same proportions as folding,
      and whether unbinding should likewise mirror binding. Using continuum-space
      calculations which extend previous kinetic analyses, we demonstrate formally that
      the precise symmetry of forward and reverse processes is expected only under
      certain special conditions. Approximate symmetry will be exhibited under a
      separate set of conditions. Exact, approximate, and broken symmetry scenarios are
      verified in several ways: using numerical calculations on toy and molecular
      systems; using exact calculations on kinetic models of induced fit in protein
      ligand binding; and based on reported experimental results. The analysis
      highlights intrinsic challenges and ambiguities in the design and analysis of
      both experiments and simulations.

PMID- 21869868
TI  - IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic
      Hepatitis C Virus Infection.
AB  - Genome-wide association studies have recently identified single nucleotide
      polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict
      sustained virologic response (SVR) in patients with chronic hepatitis C virus
      (HCV) infection who are undergoing therapy with pegylated interferon (IFN) a and
      ribavirin. IL-28B encodes IFN-lambda3, a type III IFN involved in host antiviral
      immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms,
      rs1 2979860 and rs8099917, are strong pretreatment predictors of early viral
      clearance and SVR in patients with genotype 1 HCV infection. Variations in the
      distribution of IL-28B alleles may partly explain differences in SVR rates among
      ethnic groups. Further investigations have implicated IL-28B in the development
      of chronic HCV infection versus spontaneous resolution of acute infection and
      suggest that IL-28B may be a key factor involved in host immunity against HCV.
      Clinical trials of IFN-lambda as a therapeutic agent for chronic HCV infection
      are currently underway. The use of IL-28B polymorphisms as a predictive tool will
      have a major impact on treatment strategies for chronic HCV infection,
      particularly in the context of emerging therapies and direct-acting antiviral
      agents.

PMID- 21869870
TI  - Management of Post-ERCP Pancreatitis.

PMID- 21869869
TI  - Targeting mucosal healing in Crohn's disease.
AB  - The goal of medical treatment for Crohn's disease includes improving patients'
      quality of life while reducing the need for hospitalization and surgery. The
      current medical armamentarium includes 5-aminosalicylates, corticosteroids,
      immunomodulators, and biologic agents. In the past, response to treatment was
      measured by clinical improvement in symptoms; however, with the advent of disease
      modifying medications, mucosal healing has emerged as an increasingly important
      goal of therapy. Mucosal healing, or endoscopic remission, is associated with
      increased rates of clinical remission, fewer hospitalizations, and fewer
      abdominal surgeries. Both the immunomodulator and biologic classes of medications
      are effective at inducing mucosal healing. Despite several limitations, mucosal
      healing has become a desirable and valid measure of disease activity.

PMID- 21869871
TI  - Fecal biomarkers for the diagnosis and management of inflammatory bowel disease.

PMID- 21869872
TI  - Pancreatic enzyme therapy for pancreatic exocrine insufficiency.

PMID- 21869873
TI  - Genome-Wide Association Studies: "SNPing" Away at Liver Disease.

PMID- 21869874
TI  - GERD in Minority Populations.

PMID- 21869875
TI  - Cap polyposis with protein-losing enteropathy.

PMID- 21869876
TI  - A multidisciplinary approach to the diagnosis and management of multiple
      colorectal polyps.

PMID- 21869877
TI  - Mean field strategies induce unrealistic non-linearities in calcium puffs.
AB  - Mean field models are often useful approximations to biological systems, but
      sometimes, they can yield misleading results. In this work, we compare mean field
      approaches with stochastic models of intracellular calcium release. In
      particular, we concentrate on calcium signals generated by the concerted opening
      of several clustered channels (calcium puffs). To this end we simulate calcium
      puffs numerically and then try to reproduce features of the resulting calcium
      distribution using mean field models were all the channels open and close
      simultaneously. We show that an unrealistic non-linear relationship between the
      current and the number of open channels is needed to reproduce the simulated
      puffs. Furthermore, a single channel current which is five times smaller than the
      one of the stochastic simulations is also needed. Our study sheds light on the
      importance of the stochastic kinetics of the calcium release channel activity to
      estimate the release fluxes.

PMID- 21869878
TI  - Is There a Relationship between Language Switching and Executive Functions in
      Bilingualism? Introducing a within group Analysis Approach.
AB  - Several studies have suggested a bilingual advantage in executive functions,
      presumably due to bilinguals' massive practice with language switching that
      requires executive resources, but the results are still somewhat controversial.
      Previous studies are also plagued by the inherent limitations of a natural groups
      design where the participant groups are bound to differ in many ways in addition
      to the variable used to classify them. In an attempt to introduce a complementary
      analysis approach, we employed multiple regression to study whether the
      performance of 30- to 75-year-old Finnish-Swedish bilinguals (N = 38) on tasks
      measuring different executive functions (inhibition, updating, and set shifting)
      could be predicted by the frequency of language switches in everyday life (as
      measured by a language switching questionnaire), L2 age of acquisition, or by the
      self-estimated degree of use of both languages in everyday life. Most consistent
      effects were found for the set shifting task where a higher rate of everyday
      language switches was related to a smaller mixing cost in errors. Mixing cost is
      thought to reflect top-down management of competing task sets, thus resembling
      the bilingual situation where decisions of which language to use has to be made
      in each conversation. These findings provide additional support to the idea that
      some executive functions in bilinguals are affected by a lifelong experience in
      language switching and, perhaps even more importantly, suggest a complementary
      approach to the study of this issue.

PMID- 21869879
TI  - PARADOXICAL RESPONSES TO NEUROTOXIC STERYL GLYCOSIDES: INSIGHTS FROM A CELLULAR
      MODEL OF ALSPDC.
AB  - The causes of many sporadic neurodegenerative diseases remain unknown making
      prevention difficult, if not impossible. One clue comes from the study of
      amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) of Guam
      which shares many similarities with amyotrophic lateral sclerosis, Parkinson's
      disease, and Alzheimer's disease seen in other parts of the world. This disorder
      may provide a unique opportunity to study the cause and progression of
      neurodegenerative diseases. Epidemiological and experimental findings indicate
      that dietary consumption of cycad seeds is an underlying cause of ALS-PDC. Our
      laboratory provided evidence that a family of compounds called steryl glycosides
      are the active ingredients that may be responsible for producing the
      neurodegenerative outcome in ALS-PDC. Here, we review some of our work on the
      chronic toxicity of steryl glycosides in neuronal cells maintained in cell
      culture and in an in vivo mouse model. The current studies indicate some
      mechanisms about how neuronal cells respond to this class of toxins.

PMID- 21869880
TI  - On the Usage of GPUs for Efficient Motion Estimation in Medical Image Sequences.
AB  - Images are ubiquitous in biomedical applications from basic research to clinical
      practice. With the rapid increase in resolution, dimensionality of the images and
      the need for real-time performance in many applications, computational
      requirements demand proper exploitation of multicore architectures. Towards this,
      GPU-specific implementations of image analysis algorithms are particularly
      promising. In this paper, we investigate the mapping of an enhanced motion
      estimation algorithm to novel GPU-specific architectures, the resulting
      challenges and benefits therein. Using a database of three-dimensional image
      sequences, we show that the mapping leads to substantial performance gains, up to
      a factor of 60, and can provide near-real-time experience. We also show how
      architectural peculiarities of these devices can be best exploited in the benefit
      of algorithms, most specifically for addressing the challenges related to their
      access patterns and different memory configurations. Finally, we evaluate the
      performance of the algorithm on three different GPU architectures and perform a
      comprehensive analysis of the results.

PMID- 21869881
TI  - NF-kappaB-inducing kinase increases renal tubule epithelial inflammation
      associated with diabetes.
AB  - The impact of increased NF-kappaB-inducing kinase (NIK), a key component of the
      NF-kappaB activation pathways, on diabetes-induced renal inflammation remains
      unknown. We overexpressed NIK wild type (NIKwt) or kinase-dead dominant negative
      mutants (NIKdn) in HK-2 cells and demonstrated that RelB and p52, but not RelA,
      abundance and DNA binding increased in nuclei of NIKwt but not NIKdn
      overexpressed cells, and this corresponded with increases in multiple
      proinflammatory cytokines. Since TRAF3 negatively regulates NIK expression, we
      silenced TRAF3 by >50%; this increased nuclear levels of p52 and RelB, and
      transcript levels of proinflammatory cytokines and transcription factors. In HK-2
      cells and mouse primary proximal tubule epithelial cells treated with
      methylglyoxal-modified albumin, multiple proinflammatory cytokines and NIK were
      increased in association with increased nuclear RelB and p52. These observations
      indicate that NIK regulates proinflammatory responses of renal proximal tubular
      epithelial cells via mechanisms involving TRAF3 and suggest a role for NF-kappaB
      noncanonical pathway activation in modulating diabetes-induced inflammation in
      renal tubular epithelium.

PMID- 21869882
TI  - Amniotic membrane as a scaffold for melanocyte transplantation in patients with
      stable vitiligo.
AB  - Vitiligo is an acquired skin disease that significantly impacts the quality of
      life of patients. Medical treatment of vitiligo includes the use of melanocyte
      transplant, but the results are variable. We have treated 4 patients with either
      focal or generalized stable vitiligo using a graft of autologous melanocytes'
      culture on a denuded amniotic membrane (AM). A culture biopsy was obtained in
      every patient and grown in melanocytes' media for 10-14 days after which cells
      were transferred to a denuded AM and transplanted into the achromic lesions.
      Patients were followed for up to 6 months using clinical assessment of achromic
      lesions. Treated areas ranged between 4 cm(2) and 210.6 cm(2). Response to
      treatment was excellent in all patients with 90-95% repigmentation success rate.
      Our results demonstrate that transplantation of autologous melanocytes cultured
      on AM is a new, simple, and effective treatment for stable vitiligo.

PMID- 21869883
TI  - Circulating and disseminated tumor cells in the management of advanced prostate
      cancer.
AB  - Management of prostate cancer is recognized as one of the most important medical
      problems. Latest findings concerning the role of circulating (CTC) and
      disseminated tumor cells (DTC) have provided new insights into the biology of
      metastasis with important implications for the clinical management of prostate
      cancer patients. Most of the established methods of circulating/disseminated
      tumor cell enrichment use density-gradient centrifugation and immunomagnetic
      procedures. Reverse transcriptase polymerase chain reaction is another used
      detection technique. Novel methods, the CTC-chip and the epithelial immunospot
      assay already showed promising results. For localized and metastatic prostate
      cancer, significant correlations between spreading tumor cells and well
      established indicators of disease activity have been demonstrated. Careful
      randomized prospective trials will be required to justify the routine use of
      CTCs/DTCs for therapy decision making.

PMID- 21869884
TI  - Age-related deficits in spatial memory and hippocampal spines in virgin, female
      Fischer 344 rats.
AB  - Effects of aging on memory and brain morphology were examined in aged, 21-month
      old, and young, 4-month-old, Fischer 344 female rats. Spatial memory was assessed
      using the object placement task, and dendritic spine density was determined on
      pyramidal neurons in the hippocampus following Golgi impregnation. Consistent
      with previous studies, aged females showed poorer object placement performance
      than young subjects. Young subjects significantly discriminated the location of
      objects with a 1.5-hour intertrial delay while aged subjects did not. Spine
      density of basal dendrites on CA1 pyramidal cells was 16% lower in the aged
      subjects as compared to the young subjects. No differences in spine density were
      found between young and aged subjects in basal dendrites of CA1 or in either
      dendritic field of CA3 pyramidal neurons. Thus, decreased hippocampal CA1
      dendritic spine density in aged rats may contribute to poorer spatial memory as
      compared to young rats. The possibility that the neuroplastic changes observed in
      this study may pertain only to female subjects having had a specific set of life
      experiences is discussed. Different factors, such as reproductive status, diet,
      and handling may contribute to neuroplasticity of the brain during aging;
      however, this view requires further examination.

PMID- 21869885
TI  - F-ratio test and hypothesis weighting: a methodology to optimize feature vector
      size.
AB  - Reducing a feature vector to an optimized dimensionality is a common problem in
      biomedical signal analysis. This analysis retrieves the characteristics of the
      time series and its associated measures with an adequate methodology followed by
      an appropriate statistical assessment of these measures (e.g., spectral power or
      fractal dimension). As a step towards such a statistical assessment, we present a
      data resampling approach. The techniques allow estimating sigma(2)(F), that is,
      the variance of an F-value from variance analysis. Three test statistics are
      derived from the so-called F-ratio sigma(2)(F)/F(2). A Bayesian formalism assigns
      weights to hypotheses and their corresponding measures considered (hypothesis
      weighting). This leads to complete, partial, or noninclusion of these measures
      into an optimized feature vector. We thus distinguished the EEG of healthy
      probands from the EEG of patients diagnosed as schizophrenic. A reliable
      discriminance performance of 81% based on Taken's chi, alpha-, and delta-power
      was found.

PMID- 21869887
TI  - Antigenic and Genotypic Similarity between Primary Glioblastomas and Their
      Derived Neurospheres.
AB  - Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self
      renewal, clonogenic capacities, and tumorigenicity following transplantation into
      immunodeficient mice, may denounce the existence of brain tumor stem cells
      (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS
      showed the same genetic alterations as primary tumors and the expression of
      stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum
      (FBS) to the culture, were genetically different from NS and prevailingly
      expressed differentiation antigens. NS developed from a highly malignant tumor
      phenotype with proliferation, circumscribed necrosis, and high vessel density.
      Beside originating from transformed neural stem cells (NSCs), BTSCs may be
      contained within or correspond to dedifferentiated cells after mutation
      accumulation, which reacquire the expression of stemness antigens.

PMID- 21869886
TI  - Platelet function in patients with diabetes mellitus: from a theoretical to a
      practical perspective.
AB  - Patients with diabetes mellitus have an increased prevalence of vascular disease.
      Pathologic thrombosis associated with atherosclerotic plaque rupture is a major
      cause of morbidity and mortality. Platelets are intimately involved in the
      initiation and propagation of thrombosis. Evidence suggests that platelets from
      patients with type 2 diabetes have increased reactivity and baseline activation
      compared to healthy controls. We review the pathophysiology of platelet
      hyperreactivity in DM patients and its implications in clinical practice, with
      particular focus on acute coronary syndromes, percutaneous coronary intervention,
      and novel antiplatelet agents.

PMID- 21869888
TI  - Tobacco and the escalating global cancer burden.
AB  - The global burden of cancer is escalating as a result of dramatic increases in
      the use of tobacco in the developing world. The use of tobacco is linked to the
      development of a broad variety of cancers, mainly lung cancer, the single most
      common cancer in the world. Tobacco smoking-attributable deaths extends beyond
      cancer and include stroke, heart attack and COPD. Widening disparities in cancer
      related mortality have shifted towards a more dramatic burden in the developing
      world. Appropriate interventions must be implemented to reduce tobacco use and
      prevent global mortality that has escalated to epidemic levels. Tobacco control
      policies, including public health advertisement campaigns, warning labels,
      adoption of smoke-free laws, comprehensive bans and tax policies are highly
      effective measures to control tobacco use. Clinicians and academic institutions
      have to be actively committed to support tobacco control initiatives. The
      reduction in cancer related morbidity and mortality should be viewed as a global
      crisis and definitive results will depend on a multilevel effort to effectively
      reduce the burden of cancer, particularly in underprivileged regions of the
      world.

PMID- 21869889
TI  - A Cohort Study of p53 Mutations and Protein Accumulation in Benign Breast Tissue
      and Subsequent Breast Cancer Risk.
AB  - Mutations in the p53 tumor suppressor gene and accumulation of its protein in
      breast tissue are thought to play a role in breast carcinogenesis. However, few
      studies have prospectively investigated the association of p53 immunopositivity
      and/or p53 alterations in women with benign breast disease in relation to the
      subsequent risk of invasive breast cancer. We carried out a case-control study
      nested within a large cohort of women biopsied for benign breast disease in order
      to address this question. After exclusions, 491 breast cancer cases and 471
      controls were available for analysis. Unconditional logistic regression was used
      to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53
      immunopositivity nor genetic alterations in p53 (either missense mutations or
      polymorphisms) was associated with altered risk of subsequent breast cancer.
      However, the combination of both p53 immunopositivity and any p53 nucleotide
      change was associated with an approximate 5-fold nonsignificant increase in risk
      (adjusted OR 4.79, 95% CI 0.28-82.31) but the confidence intervals were extremely
      wide. Our findings raise the possibility that the combination of p53 protein
      accumulation and the presence of genetic alterations may identify a group at
      increased risk of breast cancer.

PMID- 21869890
TI  - Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides
      of Human Chorionic Gonadotropin beta Subunit to the N-Terminal and C-Terminal
      Coding Sequence.
AB  - A new analog of EPO was designed by fusing one and two CTPs to the N-terminal and
      C-terminal ends of EPO (EPO-(CTP)(3)), respectively. This analog was expressed
      and secreted efficiently in CHO cells. The in vitro test shows that the activity
      of EPO-(CTP)(3) in TFI-1 cell proliferation assay is similar to that of EPO-WT
      and commercial rHEPO. However, in vivo studies indicated that treatment once a
      week with EPO-(CTP)(3) (15 MUg/kg) dramatically increased (~8 folds) haematocrit
      as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP)(3) is more
      effective than rHuEPO and Aranesp in increasing reticulocyte number in mice
      blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP)(3)
      following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These
      data established the rational for using this chimera as a long-acting EPO analog
      in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in
      higher animals and in human clinical trials.

PMID- 21869891
TI  - Marked mydriasis and neuritis nervi optici associated with galactorrhea following
      citalopram treatment: a case report and discussion.
AB  - We report the case of a 25-year-old women suffering from major depression who was
      treated with citalopram for several weeks with doses between 20 mg and 60 mg. She
      gradually developed marked mydriasis within 2 months after treatment and
      subsequently neuritis nervi optici. Moreover, abrupt galactorrhea occurred after
      2 months of treatment. All neuro-ophthalmological, neurophysiological, clinical
      laboratory, and neuroradiological diagnostic efforts did not reveal an underlying
      organic pathophysiology. The ocular symptoms disappeared rapidly after the
      discontinuation of citalopram and pulse therapy with methyl-prednisolone.
      However, galactorrhea persisted for a few weeks necessitating treatment with
      bromocriptine.

PMID- 21869892
TI  - Management of kikuchi-fujimoto disease using glucocorticoid: a case report.
AB  - Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is
      a self-limiting, benign, and rare systemic lymphadenitis with unknown etiology.
      The cardinal symptoms are fever, lymphadenopathy and night sweat; consequently,
      it is first necessary to rule out infectious, lymphoproliferative, and connective
      tissue diseases such as systemic lupus erythematosus. Histology can allow
      diagnosis by demonstrating necrotizing histiocyte lymphadenitis. Disease, which
      has no specific treatment, self-limits itself in 1 to 6 months clinically.
      However, non-steroid anti-inflammatory agents can be given for symptomatic
      treatment and there are reports using corticosteroids and antibiotics in
      complicated cases. This article concerns a 32-years-old female who diagnosed
      Kikuchi-Fujimoto disease and treated with glucocorticoid.

PMID- 21869894
TI  - Massive Uterine Leiomyoma in a Patient with Friedreich's Ataxia: Is There a
      Possible Association?
AB  - A possible association between Friedreich's ataxia (FA) and neoplastic
      development has been recognized. FA patients have low frataxin levels and
      insufficient response to oxidative stress. In these patients fibroblasts are
      characterized by a high rate of mutations. Herein, a case of a 39-year-old woman
      with FA tetraplegia, who was admitted in our department with intestinal
      obstruction due to a huge uterine tumor, is described. An abdominal CT revealed a
      huge intra-abdominal mass originating from the right cornu of the uterus. Tumor
      excision and adhesionlysis were performed. The histological examination of the
      tumor revealed a leiomyoma. FA patients seem to present with a variety of
      neoplasms uncommon for their young age. This is the first report of a leiomyoma
      originating from the genital system in a female patient with FA tetraplegia.
      Therefore it is important to identify neoplasms at an early stage in patients
      with FA and start immediate therapy.

PMID- 21869893
TI  - Primary Pulmonary Epithelioid Hemangioendothelioma: A Rare Cause of PET-Negative
      Pulmonary Nodules.
AB  - We report here a case of primary pulmonary epithelioid hemangioendothelioma
      diagnosed in a 67-year-old Caucasian man, presenting with exertion dyspnoea, dry
      cough, and multiple bilateral pulmonary nodules revealed by computed tomography.
      At the 18F-fluorodeoxyglucose positron emission tomography, these nodules were
      negative. The histopathological diagnosis was made on a pulmonary wedge resection
      (performed during video-thoracoscopic surgery).

PMID- 21869895
TI  - The tonsils revisited: review of the anatomical localization and histological
      characteristics of the tonsils of domestic and laboratory animals.
AB  - This paper gives an overview of the anatomical localization and histological
      characteristics of the tonsils that are present in ten conventional domestic
      animal species, including the sheep, goat, ox, pig, horse, dog, cat, rabbit, rat,
      and pigeon. Anatomical macrographs and histological images of the tonsils are
      shown. Six tonsils can be present in domestic animals, that is, the lingual,
      palatine, paraepiglottic, pharyngeal, and tubal tonsils and the tonsil of the
      soft palate. Only in the sheep and goat, all six tonsils are present. Proper
      tonsils are absent in the rat, and pigeon. In the rabbit, only the palatine
      tonsils can be noticed, whereas the pig does not present palatine tonsils. The
      paraepiglottic tonsils lack in the ox, horse, and dog. In addition, the dog and
      cat are devoid of the tubal tonsil and the tonsil of the soft palate.

PMID- 21869896
TI  - Inhibition of Human Cervical Cancer Cell Growth by Ethanolic Extract of
      Boerhaavia diffusa Linn. (Punarnava) Root.
AB  - In Indian traditional medicine, Boerhaavia diffusa (punarnava) roots have been
      widely used for the treatment of dyspepsia, jaundice, enlargement of spleen,
      abdominal pain and as an anti-stress agent. Pharmacological evaluation of the
      crude ethanolic extract of B. diffusa roots has been shown to possess
      antiproliferative and immunomodulatory properties. The extract of B. diffusa was
      studied for anti-proliferative effects on the growth of HeLa cells and for its
      effect on cell cycle. Bio-assays of extracts from B. diffusa root showed that a
      methanol : chloroform fraction (BDF 5) had an antiproliferative effect on HeLa
      cells. After 48 h of exposure, this fraction at a concentration of 200 MUg mL(-1)
      significantly reduced cell proliferation with visible morphological changes in
      HeLa cells. Cell cycle analysis suggests that antiproliferative effect of BDF 5
      could be due to inhibition of DNA synthesis in S-phase of cell cycle in HeLa
      cells, whereas no significant change in cell cycle was detected in control cells.
      The fraction BDF 5 caused cell death via apoptosis as evident from DNA
      fragmentation and caspase-9 activation. Thus the extract has potential to be
      evaluated in detail to assess the molecular mechanism-mediated anticancer
      activities of this plant.

PMID- 21869898
TI  - Distribution and Abundance of Archaea in South China Sea Sponge Holoxea sp. and
      the Presence of Ammonia-Oxidizing Archaea in Sponge Cells.
AB  - Compared with bacterial symbionts, little is known about archaea in sponges
      especially about their spatial distribution and abundance. Understanding the
      distribution and abundance of ammonia-oxidizing archaea will help greatly in
      elucidating the potential function of symbionts in nitrogen cycling in sponges.
      In this study, gene libraries of 16S rRNA gene and ammonia monooxygenase subunit
      A (amoA) genes and quantitative real-time PCR were used to study the spatial
      distribution and abundance of archaea in the South China Sea sponge Holoxea sp.
      As a result, Holoxea sp. specific AOA, mainly group C1a (marine group I:
      Crenarchaeota) were identified. The presence of ammonia-oxidizing crenarchaea was
      observed for the first time within sponge cells. This study suggested a close
      relationship between sponge host and its archaeal symbionts as well as the
      archaeal potential contribution to sponge host in the ammonia-oxidizing process
      of nitrification.

PMID- 21869897
TI  - Acupuncture Attenuates Anxiety-Like Behavior by Normalizing Amygdaloid
      Catecholamines during Ethanol Withdrawal in Rats.
AB  - Previously, we demonstrated acupuncture at acupoint HT7 (Shen-Men) attenuated
      ethanol withdrawal syndrome by normalizing the dopamine release in nucleus
      accumbens shell. In the present study, we investigated the effect of acupuncture
      on anxiety-like behavior in rats and its relevant mechanism by studying neuro
      endocrine parameters during ethanol withdrawal. Rats were treated with 3 g kg(
      1)day(-1) of ethanol (20%, w/v) or saline by intraperitoneal injections for 28
      days. The rats undergoing ethanol withdrawal exhibited anxiety-like behavior 72 h
      after the last dose of ethanol characterized by the decrease of time spent in the
      open arms of the elevated plus maze compared with the saline-treated rats (P <
      .05). Radioimmunoassay exhibited there were notably increased concentrations of
      plasma corticosterone in ethanol-withdrawn rats compared with saline-treated rats
      (P < .05). Additionally, high performance liquid chromatography analysis also
      showed the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were
      markedly increased while the levels of dopamine and 3,4-dihydroxyphenylacetic
      acid were significantly decreased in the central nucleus of the amygdala of
      ethanol-withdrawn rats compared with saline-treated rats (P < .01). Acupuncture
      groups were treated with acupuncture at acupoint HT7 or PC6 (Nei-Guan).
      Acupuncture at HT7 but not PC6 greatly attenuated the anxiety-like behavior
      during ethanol withdrawal as evidenced by significant increases in the percentage
      of time spent in open arms (P < .05). In the meantime, acupuncture at HT7 also
      markedly inhibited the alterations of neuro-endocrine parameters induced by
      ethanol withdrawal (P < .05). These results suggest that acupuncture may
      attenuate anxiety-like behavior during ethanol withdrawal through regulation of
      neuro-endocrine system.

PMID- 21869899
TI  - Phytomedicinal Role of Pithecellobium dulce against CCl(4)-mediated Hepatic
      Oxidative Impairments and Necrotic Cell Death.
AB  - Present study investigates the beneficial role of the aqueous extract of the
      fruits of Pithecellobium dulce (AEPD) against carbon tetrachloride (CCl(4))
      induced hepatic injury using a murine model. AEPD has been found to possess free
      radical (DPPH, hydroxyl and superoxide) scavenging activity in cell-free system.
      CCl(4) exposure increased the activities of various serum maker enzymes and
      intracellular reactive oxygen species (ROS) production. In line with these
      findings, we also observed that CCl(4) intoxication increased the lipid
      peroxidation and protein carbonylation accompanied by decreased intracellular
      antioxidant defense, activity of cytochrome P450 and CYP2E1 expression. DNA
      fragmentation and flow cytometric analyses revealed that CCl(4) exposure caused
      hepatic cell death mainly via the necrotic pathway. Treatment with AEPD both pre-
      and post-toxin exposure protected the organ from CCl(4)-induced hepatic damage.
      Histological findings also support our results. A well-known antioxidant vitamin
      C was included in this study to compare the antioxidant potency of AEPD.
      Combining all, results suggest that AEPD protects murine liver against CCl(4)
      induced oxidative impairments probably via its antioxidative property.

PMID- 21869900
TI  - The effect of lavender aromatherapy on autonomic nervous system in midlife women
      with insomnia.
AB  - The objective of this study is to determine the effects of 12 weeks of lavender
      aromatherapy on self-reported sleep and heart rate variability (HRV) in the
      midlife women with insomnia. Sixty-seven women aged 45-55 years, with a CPSQI
      (Chinese version of Pittsburgh Sleep Quality Index) greater than 5, were
      recruited from communities in Taiwan. The experimental group (n = 34) received
      lavender inhalation, 20 min each time, twice per week, for 12 weeks, with a total
      of 24 times. The control group (n = 33) received health education program for
      sleep hygiene with no intervention. The study of HRV was analyzed by time- and
      frequency-domain methods. Significant decrease in mean heart rate (HR) and
      increases in SDNN (standard deviation of the normal-to-normal (NN) intervals),
      RMSDD (square root of the mean squared differences of successive NN intervals),
      and HF (high frequency) of spectral powers analysis after lavender inhalation
      were observed in the 4th and 12th weeks of aromatherapy. The total CPSQI score of
      study subjects was significantly decreased in the experimental group (P < 0.001),
      while no significant difference was observed across the same time period (P =
      0.776) in the control group. Resting HR and HRV measurements at baseline 1 month
      and 3 months after allocation showed no significant difference between the
      experimental and control groups. The study demonstrated that lavender inhalation
      may have a persistent short-term effect on HRV with an increase in
      parasympathetic modulation. Women receiving aromatherapy experienced a
      significant improvement in sleep quality after intervention. However, lavender
      aromatherapy does not appear to confer benefit on HRV in the long-term followup.

PMID- 21869901
TI  - Hepatoprotective and Antioxidative Activities of Cornus officinalis against
      Acetaminophen-Induced Hepatotoxicity in Mice.
AB  - The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian
      countries as a tonic formula. In this study, the hepatoprotective effect of
      ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a
      mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice
      with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP
      (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST,
      ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP
      induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA)
      and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and
      glutathione. Liver injury and collagen accumulation were assessed using
      histological studies by hematoxylin and eosin staining. Our results indicate that
      ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by
      preventing or alleviating oxidative stress.

PMID- 21869902
TI  - Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC
      Patients: Clinical Trial.
AB  - To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects
      of chemotherapy and improving the antioxidant status of colorectal cancer (CRC)
      patients, a randomized clinical trial was conducted. Patients (43) undergoing
      adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin
      (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300
      mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as
      a control. Blood samples were collected before each of the 6 cycles of
      chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic
      parameters, and adverse events were analyzed. The use of 300 mg of Uncaria
      tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed
      parameters, and no toxic effects were observed.

PMID- 21869903
TI  - Chinese herbal formula xiao yao san for treatment of depression: a systematic
      review of randomized controlled trials.
AB  - Objectives. To assess the beneficial and adverse effects of Xiaoyaosan for
      depression. Search Strategy. Electronic databases were searched until December
      2009. Inclusion Criteria. We included randomized clinical trials testing
      Xiaoyaosan against placebo, antidepressants, or combined with antidepressants
      against antidepressants alone. Data Extraction and Analyses. Study selection,
      data extraction, quality assessment, and data analyses were conducted according
      to the Cochrane standards. Results. 26 randomized trials (involving 1837
      patients) were included and the methodological quality was evaluated as generally
      low. The pooled results showed that Xiaoyaosan combined with antidepressants was
      more effective in comprehensive effect, the score of HAMD and the score of SDS
      compared with antidepressants alone. Xiaoyaosan was superior to antidepressants
      for the score of HAMD. However, Xiaoyaosan was not different from placebo for the
      score of SDS. There was no adverse effects reported in the trials from
      Xiaoyaosan. Conclusions. Xiaoyaosan appears to be effective on improving symptoms
      in patients with depression. However, due to poor methodological quality in the
      majority of included trials, the potential benefit from Xiaoyaosan need to be
      confirmed in rigorous trials and the design and reporting of trials should follow
      international standards.

PMID- 21869904
TI  - Strategies to engage clinical staff in subject recruitment.
AB  - PURPOSE: In many countries, meeting subject recruitment goals is challenging for
      researchers relying on clinical staff members (CSMs) to identify or recruit
      subjects. This paper describes research strategies that improved staff engagement
      in three different studies conducted in US clinical settings.  METHOD: The
      recruitment strategies described in this paper were identified during the process
      of consultation among three US researchers recruiting via CSMs. Strategies which
      successfully engaged CSMs are described.  RESULTS: Our approach improved
      engagement with CSMs in three different US studies. Early engagement strategies
      included establishing trust, gathering input from CSMs, and using succinct
      training procedures as well as a study logo. Middle phase strategies included
      assigning recruitment, publishing a study newsletter, giving the CSMs
      compensation and appreciation for their participation, and expanding the subject
      pool. Completion strategies included closing with an appreciation meeting and
      adding merit letters to personnel files.  CONCLUSION: Recruitment of an adequate
      number of subjects is often challenging, even within clinical settings where
      subject populations are abundant. CSMs have rightly prioritised clinical care
      over directing subjects to research studies. It is therefore critical that
      researchers recruiting in such clinical settings anticipate recruitment
      challenges and plan to implement appropriate engagement strategies in all phases
      of research.

PMID- 21869905
TI  - In LNCaP cells enhanced expression of the androgen receptor compensates for Bcl-2
      suppression by antisense oligonucleotides.
AB  - BACKGROUND AND METHODS: Antisense oligonucleotides (oligos) have been employed
      against in vivo and in vitro prostate cancer models targeting growth stimulatory
      gene products. While most oligos have targeted growth factors or their receptors,
      others have been directed against inhibitors of apoptosis. In LNCaP cells we
      evaluated a set of oligos which targeted and comparably suppressed the expression
      of the apoptosis inhibitor protein Bcl-2. LNCaP cells adapted to this restoration
      of apoptosis with a compensatory suppression of caspase-3 expression, a
      nontargeted promoter of this process. In a continuation of this study we now
      evaluate the expression of the androgen receptor (AR) following oligo mediated
      regulation of apoptosis with suppression of Bcl-2. RESULTS: Monospecific and
      bispecific oligos directed against Bcl-2 suppressed both the targeted Bcl-2
      protein (an inhibitor of apoptosis) and the nontargeted caspase-3 (a promoter of
      apoptosis), potentially negating the effect on apoptosis produced by specific
      inhibition of Bcl-2. In contrast, the expression of the AR was significantly
      enhanced by each type of oligo. CONCLUSIONS: This suggests that when Bcl-2
      expression is inhibited there are compensatory changes in the expression of
      additional proteins which regulate tumor growth, apoptosis and cell survival, and
      in this scenario might increase or re-establish hormonal sensitivity. If tumors
      variants are selected which evade gene therapy additional mechanisms of
      compensation must be identified and subsequently suppressed. These experiments
      identify pathways by which tumors can develop resistance to gene therapy and
      suggests additional targets for intervention.

PMID- 21869906
TI  - Difficulties with access in percutaneous renal surgery.
AB  - Percutaneous renal surgery provides a minimally invasive approach to the kidney
      for stone extraction in a number of different clinical scenarios. Certain
      clinical cases present inherent challenges to percutaneous access to the kidney.
      Herein, we present scenarios in which obtaining and/or maintaining percutaneous
      access is difficult along with techniques to overcome the challenges commonly
      encountered. Also, complications associated with these challenging percutaneous
      renal surgeries are discussed.

PMID- 21869907
TI  - Upper urinary tract urothelial carcinoma: what have we learned in the last 4
      years?
AB  - In the last 4 years many studies have been published on the topic of upper
      urinary tract urothelial carcinoma (UTUC). This is a recent review of the
      available literature of the last 3 years. A systematic Medline/PubMed search on
      UTUC including limits for clinical trials and randomized, controlled trials was
      performed for English-language articles using the keywords 'upper urinary tract
      carcinoma', 'nephroureterectomy', 'laparoscopic', 'ureteroscopy', 'percutaneous',
      'renal pelvis', 'ureter' and their combinations from January 2008 to December
      2010. Additional selected reports from 2007 were included. Case reports and non
      English literature were excluded. Publications were mostly retrospective,
      including some large, multicentre studies from the Upper Tract Urothelial
      Carcinoma Collaboration (UTUCC). The authors of this article are members of the
      UTUCC. Altogether, 92 original articles dealing with UTUC were identified and
      summarized. The vast majority of the available literature has a low level of
      evidence (level IV), although many multicentre studies tried to overcome the
      problem of low numbers by pooling data. It was concluded that in the last 3 years
      our knowledge regarding UTUC has increased dramatically, although new study
      concepts allowing us to increase the level of evidence are needed.

PMID- 21869908
TI  - The evolution of lasers in urology.
AB  - The world's first laser was developed by Theodore Maiman in 1960. Over the course
      of the past five decades, this technology has evolved into a highly specialized
      entity, also finding a niche market in the field of urology. Lasers obtained from
      various lasing mediums producing amplified light of different wavelengths have
      been tested for urological applications. Today, these lasers are most commonly
      used in the surgical management of benign prostatic hyperplasia and as
      intracorporeal lithotripters. Other uses include ablation of various urologic
      tumors and incising strictures of the upper- and lower urinary tract. A
      continuous process of evolution of this technology is taking place, resulting in
      surgical lasers becoming ever safer, more effective, and more affordable.

PMID- 21869909
TI  - History and Future of Multi-Institutional Clinical Trials in Urinary
      Incontinence.

PMID- 21869910
TI  - DNA methylation profiling in nanochannels.
AB  - We report the profiling of the 5-methyl cytosine distribution within single
      genomic-sized DNA molecules at a gene-relevant resolution. This method linearizes
      and stretches DNA molecules by confinement to channels with a dimension of about
      250*200 nm(2). The methylation state is detected using fluorescently labeled
      methyl-CpG binding domain proteins (MBD), with high signal contrast and low
      background. DNA barcodes consisting of methylated and non-methylated segments are
      generated, with both short and long concatemers demonstrating spatially resolved
      MBD binding. The resolution of the technique is better than 10 kbp, and single
      molecule read-lengths exceeding 140 kbp have been achieved.

PMID- 21869911
TI  - Molecular Imaging of Healing After Myocardial Infarction.
AB  - The progression from acute myocardial infarction (MI) to heart failure continues
      to be a major cause of morbidity and mortality. Potential new therapies for
      improved infarct healing such as stem cells, gene therapy, and tissue engineering
      are being investigated. Noninvasive imaging plays a central role in the
      evaluation of MI and infarct healing, both clinically and in preclinical
      research. Traditionally, imaging has been used to assess cardiac structure,
      function, perfusion, and viability. However, new imaging methods can be used to
      assess biological processes at the cellular and molecular level. We review
      molecular imaging techniques for evaluating the biology of infarct healing and
      repair. Specifically, we cover recent advances in imaging the various phases of
      MI and infarct healing such as apoptosis, inflammation, angiogenesis,
      extracellular matrix deposition, and scar formation. Significant progress has
      been made in preclinical molecular imaging, and future challenges include
      translation of these methods to clinical practice.

PMID- 21869912
TI  - Behcet's Syndrome and Thrombosis.
AB  - Behcet syndrome (BS) is a multisystem vasculitis with unknown etiology and a
      unique geographic distribution. The disease course is characterized by
      exacerbations and remissions while abating as the years pass. The usual onset is
      in the third decade. Recurrent skin mucosa lesions and sight threatening
      panuveitis are the hallmark of the disease. Males are more severely affected than
      females. Vascular involvement can occur in up to 40% of cases. BS is unique among
      the vasculitides in that it may involve all sizes and types of vessels. It
      affects the veins more than the arteries. Lower extremity vein thrombosis is the
      most frequent manifestation of vascular involvement, followed by vena cava
      thrombosis, pulmonary artery aneurysms, Budd-Chiari syndrome, peripheral artery
      aneurysms, dural sinus thrombosis and abdominal aorta aneurysms. Vascular
      involvement is frequently associated with constitut onal symptoms and increased
      acute phase response and is the major cause of increased mortality. A
      predominantly neutrophilic vasculitis around the vaso vasorum is typical of BS.
      The thrombus is tightly adherent to the vessel wall which probably explains why
      thromboembolism is so rare despite the high frequency of venous disease.
      Thrombophilic factors do not seem to explain thrombotic tendency in BS.
      Immunosuppressive treatment is essential in suppression and preventing the
      attacks.

PMID- 21869913
TI  - Splanchnic vein thrombosis in the mediterranean area in children.
AB  - Abdominal venous thrombosis may present as splanchnic venous thrombosis (SVT)
      (occlusion of portal, splenic, superior or inferior mesenteric veins) or Budd-
      Chiari Syndrome (BCS) (thrombosis of inferior vena cava and/or hepatic veins).
      The aim of this review is to report the scanty data available for SVT in the
      South Mediterranean area. In one Egyptian study, the possible circumstantial risk
      factors for portal vein thrombosis (PVT) were found in 30% of cases: 19% neonatal
      sepsis, 8.7% umbilical catheterization, 6% severe gastroenteritis and
      dehydration. Another Egyptian study concluded that hereditary thrombophilia was
      common in children with PVT (62.5%), the commonest being factor V Leiden mutation
      (FVL) (30%). Concurrence of more than one hereditary thrombophilia was not
      uncommon (12.5%). The first international publication on hepatic veno-occlusive
      disease (VOD) in Egypt was in 1965 in children who rapidly develop abdominal
      distention with ascites and hepatomegaly. This disease was more frequent in
      malnourished children coming from rural areas; infusions given at home may
      contain noxious substances that were hepatotoxic and infections might play a
      role. VOD of childhood is rarely seen nowadays. Data from South Mediterranean
      area are deficient and this may be attributable to reporting in local medical
      journals that are difficult to access. Medical societies concerned with this
      topic could help distribute this information.

PMID- 21869914
TI  - The role of infection in the pathogenesis of vaso-occlusive crisis in patients
      with sickle cell disease.
AB  - Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive crisis
      (VOC). Patients with SCD have impaired immunity and are thus predispose to
      infections. The vast majority of SCD patients live in underdeveloped nations with
      high prevalence and transmission rates of infections. This makes the SCD patients
      prone to infections, which frequently precipitate VOC. We reviewed the role of
      infection in the pathogenesis of VOC, taking into consideration all potential
      mechanisms from previous studies and hypothetical perspectives. The potential
      mechanisms through which infections may lead to VOC involve several pathological
      changes including pneumonitis, pyrexia, acute phase reaction, hypercoagulability,
      neutrophilia, eosinophilia, thrombocytosis, bronchospasm, red cell cytopathic and
      membrane changes, auto-antibodies mediated red cell agglutination and
      opsonization, diarrhoea and vomiting, which may act singly or in concert to cause
      red cell sickling. These changes can induce sickling directly or indirectly
      through their adverse effects on Hb oxygenation and polymerization, hydration,
      blood viscosity, red cell metabolism, procoagulant activation, intercellular
      adherence and aggregation, culminating in VOC. There is therefore the need to
      ameliorate the burden of infection on SCD through immunization, prophylactic and
      therapeutic use of antimicrobials, barrier protection and vector control in
      communities with high prevalence of SCD.

PMID- 21869915
TI  - Cerebral venous thrombosis in the mediterranean area in children.
AB  - Cerebral Venous Sinus (sinovenous) Thrombosis (CSVT) is a serious and rare
      disorder, increasingly recognized and diagnosed in pediatric patients. The
      etiology and pathophisiology has not yet been completely clarified, and unlike
      adults with CSVT, management in children and neonates remains controversial.
      However, morbidity and mortality are significant, highlighting the continued need
      for high-quality studies within this field. The following review will highlight
      aspects of CSVT in the mediteranian area in children.

PMID- 21869916
TI  - HIV-Associated Venous Thromboembolism.
AB  - HIV infection has been recognized as a prothrombotic condition and this
      association has now been proven by a large number of studies with a reported VTE
      frequency among HIV-infected patients ranging from 0.19% to 7,63 %/year. HIV
      infection is associated with a two to tenfold increased risk of venous thrombosis
      in comparison with a general population of the same age. Some risk factors
      demonstrated a strongest association with VTE such as, low CD4(+) cell count
      especially in the presence of clinical AIDS, protein S deficiency, and protein C
      deficiency. Whereas other risk factors are still controversial like protease
      inhibitor therapy, presence of active opportunistic infections and presence of
      antiphospholipid antibodies, including anticardiolipin antibodies and lupus
      anticoagulant. Physicians caring for HIV positive patients should be able to
      recognize and treat not only the well-known opportunistic infections and
      malignancies associated with this chronic disease, but also be alert to the less
      well-known complications such as thromboses. Pulmonary embolism should be
      included in the differential diagnosis when patients with HIV/AIDS have
      unexplained dyspnea or hypoxemia. In younger individuals with VTE, especially
      men, without other identifiable risk factors for VTE, HIV should be considered.
      Because interactions between warfarin and antiretrovirals is possible, health
      care providers should also be alert to the potential of dangerously high or low
      INRs when they are giving anticoagulants to patients with HIV infection who are
      undergoing antiretroviral therapy.

PMID- 21869917
TI  - Therapy-Related Myeloid Neoplasms in Chronic Lymphocytic Leukemia and
      Waldenstrom's Macroglobulinemia.
AB  - Secondary myelodysplasia (MDS) and acute myeloid leukemia (AML) are frequent long
      term complications in Chronic Lymphocytic Leukemia (CLL) and Waldenstrom
      Macroglobulinemia (WM) patients. Although disease-related immune-suppression
      plays a crucial role in leukemogenesis there is great concern that therapy may
      further increase the risk of developing these devastating
      complications.Nucleoside analogs (NA) and alkylating agents are considered
      appropriate agents in the treatment of both CLL and WM patients. Prolonged
      immunosuppression related to NA therapy and the incorporation of these agents or
      their metabolites into DNA, with potentially mutagenic action, leads to
      speculation that their therapeutic use might be responsible for an increased
      incidence of second cancer especially when combined with other DNA damaging
      agents like alkylating agents.In this review the published studies considering
      the occurrence of secondary MDS and AML in CLL and WM patients are reported and
      the potential role of chemotherapeutic agents in leukemogenesis is discussed.

PMID- 21869918
TI  - Prognosis and therapy when acute promyelocytic leukemia and other "good risk"
      acute myeloid leukemias occur as a therapy-related myeloid neoplasm.
AB  - Treatment for a pre-existing condition using chemotherapy, radiation therapy,
      immunosuppressive therapy, or a combination of these modalities may lead to the
      devastating complication of therapy-related myelodysplastic syndrome or acute
      myeloid leukemia (t-MDS/t-AML), collectively known as therapy-related myeloid
      neoplasm (t-MN). This disorder arises as a direct consequence of mutational
      events induced by the primary treatment. The outcomes for these patients have
      been historically poor compared to people who develop AML de novo. Currently
      comprising 10-20% of all cases of AML, t-MN is relatively resistant to
      conventional leukemia therapies, and is associated with s ort survival times.
      Median life expectancy from diagnosis is about 8-10 months in most series.
      Although the spectrum of cytogenetic abnormalities in t-AML is similar to AML de
      novo, the frequency of unfavorable cytogenetics, such as a complex karyotype or
      deletion or loss of chromosomes 5 and/or 7, is considerably higher in t-MN. Two
      distinct groups of patients with t-MN have been described. The more common
      subtype, seen in about 75% of patients, typically occurs 5-7 years after first
      exposure to alkylating agents or radiation, is often preceded by a
      myelodysplastic syndrome (MDS), and is frequently accompanied by clonal
      cytogenetic abnormalities such as the loss of all or part of chromosomes 5 or 7.
      Mutations of the P53 tumor suppressor gene are also common. The risk is related
      to total cumulative exposure over time to alkylating agents. In contrast, among
      individuals who develop t-AML after treatment with topoisomerase II inhibitors,
      the latency period to the development of t-AML is often only 1-3 years,
      antecedent MDS is rare, and gene rearrangements involving MLL at 11q23 or
      RUNX1/AML1 at 21q22 are common. It is now well recognized that APL and other
      subtypes of AML with balanced translocations sometimes occur as therapy-related
      myeloid neoplasms (t-MN) in patients who have previously received cytotoxic
      therapy or ionizing radiation therapy (RT). The most of this review will focus on
      these "good risk" leukemias, i.e. those with APL or inv(16)/t(16;16) or t(8;21).

PMID- 21869919
TI  - Nonimmune Cells Contribute to Crosstalk between Immune Cells and Inflammatory
      Mediators in the Innate Response to Trypanosoma cruzi Infection.
AB  - Chagas myocarditis, which is caused by infection with the intracellular parasite
      Trypanosoma cruzi, remains the major infectious heart disease worldwide. Innate
      recognition through toll-like receptors (TLRs) on immune cells has not only been
      revealed to be critical for defense against T. cruzi but has also been involved
      in triggering the pathology. Subsequent studies revealed that this parasite
      activates nucleotide-binding oligomerization domain- (NOD-)like receptors and
      several particular transcription factors in TLR-independent manner. In addition
      to professional immune cells, T. cruzi infects and resides in different
      parenchyma cells. The innate receptors in nonimmune target tissues could also
      have an impact on host response. Thus, the outcome of the myocarditis or the
      inflamed liver relies on an intricate network of inflammatory mediators and
      signals given by immune and nonimmune cells. In this paper, we discuss the
      evidence of innate immunity to the parasite developed by the host, with emphasis
      on the crosstalk between immune and nonimmune cell responses.

PMID- 21869920
TI  - Assessing Errors Inherent in OCT-Derived Macular Thickness Maps.
AB  - SD-OCT has become an essential tool for evaluating macular pathology; however
      several aspects of data collection and analysis affect the accuracy of retinal
      thickness measurements. Here we evaluated sampling density, scan centering, and
      axial length compensation as factors affecting the accuracy of macular thickness
      maps. Forty-three patients with various retinal pathologies and 113 normal
      subjects were imaged using Cirrus HD-OCT. Reduced B-scan density was associated
      with increased interpolation error in ETDRS macular thickness plots. Correcting
      for individual differences in axial length revealed modest errors in retinal
      thickness maps, while more pronounced errors were observed when the ETDRS plot
      was not positioned at the center of the fovea (which can occur as a result of
      errant fixation). Cumulative error can exceed hundreds of microns, even under
      "ideal observer" conditions. This preventable error is particularly relevant when
      attempting to compare macular thickness maps to normative databases or measuring
      the area or volume of retinal features.

PMID- 21869921
TI  - Comparison of newly diagnosed ocular hypertension and open-angle glaucoma: ocular
      variables, risk factors, and disease severity.
AB  - Purpose. To describe the distribution of ocular variables, risk factors, and
      disease severity in newly diagnosed ocular hypertension (OH) or open-angle
      glaucoma (OAG). Methods. Eligible subjects underwent a complete history and
      examination. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs)
      obtained from multiple logistic regression models were used to compare OAG to OH
      and advanced to early/moderate OAG. Results. 405 subjects were enrolled: 292
      (72.1%) with OAG and 113 (27.9%) with OH. 51.7% had early, 27.1% moderate, and
      20.9% advanced OAG. The OR for OAG versus OH was 8.19 (P < 0.0001) for disc
      notch, 5.36 (P < 0.0001) for abnormal visual field, 1.45 (P = 0.001) for
      worsening mean deviation, 1.91 (P < 0.0001) for increased cupping, 1.03 for
      increased age (P = 0.030), and 0.36 (P = 0.010) for smoking. Conclusions.
      Increased age was a risk for OAG, and smoking decreased the risk of OAG compared
      to OH. Almost half of the OAG subjects had moderate/advanced disease at
      diagnosis.

PMID- 21869922
TI  - Evaluation of fluorescent analogs of deoxycytidine for monitoring DNA transitions
      from duplex to functional structures.
AB  - Topological variants of single-strand DNA (ssDNA) structures, referred to as
      "functional DNA," have been detected in regulatory regions of many genes and are
      thought to affect gene expression. Two fluorescent analogs of deoxycytidine,
      Pyrrolo-dC (PdC) and 1,3-diaza-2-oxophenoxazine (tC( degrees )), can be
      incorporated into DNA. Here, we describe spectroscopic studies of both analogs to
      determine fluorescent properties that report on structural transitions from
      double-strand DNA (dsDNA) to ssDNA, a common pathway in the transition to
      functional DNA structures. We obtained fluorescence-detected circular dichroism
      (FDCD) spectra, steady-state fluorescence spectra, and fluorescence lifetimes of
      the fluorophores in DNA. Our results show that PdC is advantageous in
      fluorescence lifetime studies because of a distinct ~2 ns change between paired
      and unpaired bases. However, tC( degrees ) is a better probe for FDCD experiments
      that report on the helical structure of DNA surrounding the fluorophore. Both
      fluorophores provide complementary data to measure DNA structural transitions.

PMID- 21869923
TI  - Decolorization of Solophenyl Red 3BL Polyazo Dye by Laccase-Mediator System:
      Optimization through Response Surface Methodology.
AB  - The decolorization of direct Solophenyl red 3BL (SR), a polyazo dye extensively
      used in textile industry was studied. The Fomes fomentarius laccase alone did not
      decolorize SR. The natural redox mediator, acetosyringone (AS), was necessary for
      decolorization to occur. Box-Behnken design was used to evaluate the effects of
      three parameters, namely, enzyme concentration (0.5-2.5 U mL(-1)), redox mediator
      concentration (3-30 MUM), and incubation time (1-24 h), on the SR decolorization
      yield. The fitted mathematical model allowed us to plot response surfaces as well
      as isoresponse curves and to determine optimal decolorization conditions. The
      results clearly indicated that the AS concentration was the main factor
      influencing the SR decolorization yield. The selected optimal conditions were
      enzyme concentration 0.8 U mL(-1), mediator concentration 33 MUM, and time 14 h
      30 min. These conditions allowed 79.66% of SR decolorization versus 80.70% for
      the predicted value. These results showed a promising future of applying laccase
      AS system for industrial wastewater bioremediation.

PMID- 21869924
TI  - Relative Expression Levels Rather Than Specific Activity Plays the Major Role in
      Determining In Vivo AKT Isoform Substrate Specificity.
AB  - The AKT protooncogene mediates many cellular processes involved in normal
      development and disease states such as cancer. The three structurally similar
      isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform
      specific functions; however the basis for their differential signalling remains
      unclear. Here we show that in vitro, purified AKT3 is ~47-fold more active than
      AKT1 at phosphorylating peptide and protein substrates. Despite these marked
      variations in specific activity between the individual isoforms, a comprehensive
      analysis of phosphorylation of validated AKT substrates indicated only subtle
      differences in signalling via individual isoforms in vivo. Therefore, we
      hypothesise, at least in this model system, that relative tissue/cellular
      abundance, rather than specific activity, plays the dominant role in determining
      AKT substrate specificity in situ.

PMID- 21869925
TI  - Enzyme-Catalyzed Oxidation of 17beta-Estradiol Using Immobilized Laccase from
      Trametes versicolor.
AB  - Many natural and synthetic estrogens are amenable to oxidation through the
      catalytic action of oxidative enzymes such as the fungal laccase Trametes
      versicolor. This study focused on characterizing the conversion of estradiol
      (E(2)) using laccase that had been immobilized by covalent bonding onto silica
      beads contained in a bench-scale continuous-flow packed bed reactor. Conversion
      of E(2) accomplished in the reactor declined when the temperature of the system
      was changed from room temperature to just above freezing at pH 5 as a result of a
      reduced rate of reaction rather than inactivation of the enzyme. Similarly,
      conversion increased when the system was brought to warmer temperatures. E(2)
      conversion increased when the pH of the influent to the immobilized laccase
      reactor was changed from pH 7 to pH 5, but longer-term experiments showed that
      the enzyme is more stable at pH 7. Results also showed that the immobilized
      laccase maintained its activity when treating a constant supply of aqueous E(2)
      at a low mean residence time over a 12-hour period and when treating a constant
      supply of aqueous E(2) at a high mean residence time over a period of 9 days.

PMID- 21869926
TI  - Long-term respiratory muscle endurance training in patients with myasthenia
      gravis: first results after four months of training.
AB  - Myasthenia gravis (MG) is characterized by reduced muscle endurance and is often
      accompanied by respiratory complications. Improvement of respiratory function is
      therefore an important objective in MG therapy. A previous study demonstrated
      that respiratory muscle endurance training (RMET) over four weeks increased
      respiratory muscle endurance of MG patients to about 200% of baseline. The
      purpose of the present study was to establish an appropriate maintenance training
      and to test its effects over four months. Ten patients with mild to moderate MG
      participated in this study. During the first month, they performed five training
      sessions per week. For the following 3 months, training frequency was reduced to
      five sessions per two weeks. Myasthenia score, lung function, and respiratory
      endurance were determined prior to training, after the first month, and after 4
      months. Myasthenia score improved from 0.71 +/- 0.1 to 0.56 +/- 0.1 (P = 0.007).
      Respiratory endurance time increased from 6.1 +/- 0.8 to 20.3 +/- 3.0 min (P <
      0.001). In conclusion, this RMET maintenance program is feasible and is
      significantly beneficial for MG patients.

PMID- 21869927
TI  - Associations of plasma phospholipid omega-6 and omega-3 polyunsaturated Fatty
      Acid levels and MRI measures of cardiovascular structure and function: the
      multiethnic study of atherosclerosis.
AB  - Background. The association between plasma omega-6 fatty acids and cardiovascular
      disease (CVD) is unclear, and discrepancy remains concerning the cardiovascular
      benefit of the omega-3 fatty acid alpha-linolenic acid. Methods. Associations of
      plasma phospholipid fatty acid levels (arachidonic acid, linoleic acid,
      eicosapentaenoic acid, docosahexaenoic acid (DHA), and alpha-linolenic acid) with
      cardiac magnetic resonance imaging measures of left ventricular (LV) mass, LV
      volume, ejection fraction, stroke volume, and aortic distensibility were
      investigated in 1,274 adults. Results. Results of multivariate analysis showed no
      statistically significant associations of plasma omega-6 or omega-3 levels with
      cardiac magnetic resonance imaging measures. Stratification by gender revealed a
      positive association between DHA and LV mass in women (beta = 1.89, P = 0.02; P
      interaction = 0.003) and a trend for a positive association between DHA and
      ejection fraction in men (beta = 0.009, P = 0.05; P interaction = 0.03).
      Conclusion. Additional research is warranted to clarify the effects of plasma DHA
      on cardiac structure and function in women versus men.

PMID- 21869928
TI  - Adipokines as possible new predictors of cardiovascular diseases: a case control
      study.
AB  - Background and Aims. The secretion of several adipocytokines, such as
      adiponectin, retinol-binding protein 4 (RBP4), adipocyte fatty acid binding
      protein (aFABP), and visfatin, is altered in subjects with abdominal adiposity;
      these endocrine alterations could contribute to increased cardiovascular risk.
      The aim of the study was to assess the relationship among adiponectin, RBP4,
      aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A
      case-control study, nested within a prospective cohort, on 2945 subjects enrolled
      for a diabetes screening program was performed. We studied 18 patients with
      incident fatal or nonfatal IHD (Ischemic Heart Disease) or CVD (Cerebrovascular
      Disease), compared with 18 matched control subjects. Circulating adiponectin
      levels were significantly lower in cases of IHD with respect to controls.
      Circulating RBP4 levels were significantly increased in CVD and decreased in IHD
      with respect to controls. Circulating aFABP4 levels were significantly increased
      in CVD, while no difference was associated with IHD. Circulating visfatin levels
      were significantly lower in cases of both CVD and IHD with respect to controls,
      while no difference was associated with CVD. Conclusions. The present study
      confirms that low adiponectin is associated with increased incidents of IHD, but
      not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and
      RBP4 in the development of cardiovascular disease.

PMID- 21869930
TI  - Cognitive and affective correlates of temperament in Parkinson's disease.
AB  - Parkinson's disease (PD) patients display low novelty seeking scores on the
      Tridimensional Personality Questionnaire (TPQ), which may reflect the low
      dopamine function that characterises the disease. People with PD also display
      raised harm avoidance scores. Due to these and other observations, a
      "parkinsonian personality" has been suggested. However, little is known about how
      these features relate to cognitive and affective disorders, which are also common
      in PD. We examined links between TPQ scores and performance on an attentional
      orienting task in a sample of 20 people with PD. In addition, associations
      between TPQ and depression and anxiety scores were explored. It was found that
      novelty seeking scores were significantly correlated with a reaction time measure
      of attentional orienting to visual novelty. Harm avoidance scores were
      significantly correlated with anxiety, but not depression scores. These findings
      extend our understanding of how temperament interacts with cognitive and
      affective features of the disorder.

PMID- 21869929
TI  - Dietary conjugated linoleic Acid and hepatic steatosis: species-specific effects
      on liver and adipose lipid metabolism and gene expression.
AB  - Objective. To summarize the recent studies on effect of conjugated linoleic acid
      (CLA) on hepatic steatosis and hepatic and adipose lipid metabolism highlighting
      the potential regulatory mechanisms. Methods. Sixty-four published experiments
      were summarized in which trans-10, cis-12 CLA was fed either alone or in
      combination with other CLA isomers to mice, rats, hamsters, and humans were
      compared. Summary and Conclusions. Dietary trans-10, cis-12 CLA induces a severe
      hepatic steatosis in mice with a more muted response in other species. Regardless
      of species, when hepatic steatosis was present, a concurrent decrease in body
      adiposity was observed, suggesting that hepatic lipid accumulation is a result of
      uptake of mobilized fatty acids (FA) from adipose tissue and the liver's
      inability to sufficiently increase FA oxidation and export of synthesized
      triglycerides. The potential role of liver FA composition, insulin secretion and
      sensitivity, adipokine, and inflammatory responses are discussed as potential
      mechanisms behind CLA-induced hepatic steatosis.

PMID- 21869931
TI  - TP53 Mutations and HBX Status Analysis in Hepatocellular Carcinomas from Iran:
      Evidence for Lack of Association between HBV Genotype D and TP53 R249S Mutations.
AB  - High incidence of HCC is mostly due to the combination of two major risk factors,
      chronic infection with hepatitis B (HBV) and/or C (HCV) viruses and exposure to
      the mycotoxin aflatoxin B(1), which induces a particular mutation at codon 249 in
      TP53 (R249S). Eight genotypes of HBV are diversely found in high and low
      incidence areas. Regardless of documented strong associations between TP53 R249S
      mutation and HBV genotypes B, C, A or E, there is no report of such association
      for genotype D despite of the presence of aflatoxin in areas with high prevalence
      of HBV genotype D. In Iran, 3% of the population is chronically infected with
      HBV, predominantly genotype D. Twenty-one histologically confirmed HCC cases from
      Iran were analyzed for TP53 R249S and HBV double mutations 1762(T)/1764(A),
      hallmarks of more pathogenic forms of HBV. We did not detect any of these
      mutations. In addition, we report the only case identified so far carrying both
      R249S mutation and chronic HBV genotype D, a patient from The Gambia in West
      Africa. This paper suggests that association between HBV genotype D and aflatoxin
      induced TP53 mutation is uncommon, explaining the relatively lower incidence of
      HCC in areas where genotype D is highly prevalent.

PMID- 21869932
TI  - Strategies for diagnosis and prevention of venous thromboembolism during
      pregnancy.
AB  - Pregnancy and the postpartum period have an increased incidence of venous
      thromboembolism (VTE). The condition is unique during this period for several
      reasons. Primarily, because there is complexity in diagnosing this condition in
      view of altered physiology and preexisting edema in pregnancy and also because
      there are restrictions on the use of certain drugs and a need for vigilant
      monitoring of anticoagulant activities of drugs during the period. The problem is
      compounded and assumes the highest order of significance since two lives are
      involved and all the investigations and management done should also take into
      account the potential adverse effects on the foetus. In order to prevent the
      development of VTE during pregnancy, sound clinical evaluation for risk factors,
      risk stratification, and optimal use of resource both mechanical and
      pharmacological is necessary. This paper details strategies in preventing
      development of deep vein thrombosis and treatment of VTEs.

PMID- 21869933
TI  - Acquired activated protein C resistance, thrombophilia and adverse pregnancy
      outcomes: a study performed in an Irish cohort of pregnant women.
AB  - The combination of thrombophilia and pregnancy increases the risk of thrombosis
      and the potential for adverse outcomes during pregnancy. The most significant
      common inherited risk factor for thrombophilia is activated protein C resistance
      (APCR), a poor anticoagulant response of APC in haemostasis, which is mainly
      caused by an inherited single-nucleotide polymorphism (SNP), factor V G1691A (FV
      Leiden) (FVL), referred as inherited APCR. Changes in the levels of coagulation
      factors: FV, FVIII, and FIX, and anticoagulant factors: protein S (PS) and
      protein C (PC) can alter APC function causing acquired APCR. Prothrombin G20210A
      and methylenetetrahydrofolate reductase (MTHFR) C677T are prothrombotic SNPs
      which in association with APCR can also increase the risk of thrombosis amongst
      Caucasians. In this study, a correlation between an acquired APCR phenotype and
      increased levels of factors V, VIII, and IX was demonstrated. Thrombophilic
      mutations amongst our acquired APCR pregnant women cohort are relatively common
      but do not appear to exert a severe undue adverse effect on pregnancy.

PMID- 21869934
TI  - Nanocarriers for nitric oxide delivery.
AB  - Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative,
      antibacterial, and tumoricidal effects. To study the complex and wide-ranging
      roles of NO and to facilitate its therapeutic use, a great number of synthetic
      compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and
      nitrosyl metal complexes) have been developed to chemically stabilize and release
      NO in a controlled manner. Although NO is currently being exploited in many
      biomedical applications, its use is limited by several factors, including a short
      half-life, instability during storage, and potential toxicity. Additionally,
      efficient methods of both localized and systemic in vivo delivery and dose
      control are needed. One strategy for addressing these limitations and thus
      increasing the utility of NO donors is based on nanotechnology.

PMID- 21869936
TI  - Is speciation accompanied by rapid evolution? Insights from comparing
      reproductive and nonreproductive transcriptomes in Drosophila.
AB  - The tempo and mode of evolutionary change during speciation have remained
      contentious until recently. While much of the evidence claiming speciation is an
      abrupt and rapid process comes from fossil data, recent molecular phylogenetics
      show that the background of gradual evolution is often broken by accelerated
      rates of molecular evolution during speciation. However, what kinds of genes
      affect or are affected by speciation remains unexplored. Our analysis of 4843
      protein-coding genes in five species of the Drosophila melanogaster subgroup
      shows that while ~70% of genes follow clock-like evolution, between 17-19.67% of
      loci show signatures of accelerated rates of evolution in recently formed
      species. These genes show 2-3-fold higher rates of substitution in recently
      diverged species compared to older species. This fraction of loci affects a
      diverse range of functions. Only a small proportion of reproductive genes
      experience speciation-related accelerated changes but many sex-and -reproduction
      related genes show an interesting pattern of persistent rapid evolution
      suggesting that sex-and-reproduction related genes are under constant selective
      pressures. The identification of loci associated with accelerated evolution
      allows us to address the mechanisms of rapid evolution and speciation, which in
      our study appears to be a combination of both selection and rapid demographical
      changes.

PMID- 21869937
TI  - The whole object of education is...

PMID- 21869935
TI  - The monogenean parasite fauna of cichlids: a potential tool for host
      biogeography.
AB  - We discuss geographical distribution and phylogeny of Dactylogyridea (Monogenea)
      parasitizing Cichlidae to elucidate their hosts' history. Although mesoparasitic
      Monogenea (Enterogyrus spp.) show typical vicariant distribution, ectoparasitic
      representatives from different continents are not considered sister taxa, hence
      their distribution cannot result from vicariance alone. Because of the close host
      parasite relationship, this might indicate that present-day cichlid distribution
      may also reflect dispersal through coastal or brackish waters. Loss of
      ectoparasites during transoceanic migration, followed by lateral transfer from
      other fish families might explain extant host-parasite associations. Because of
      its mesoparasitic nature, hence not subject to salinity variations of the host's
      environment, Enterogyrus could have survived marine migrations, intolerable for
      ectoparasites. Host-switches and salinity transitions may be invoked to explain
      the pattern revealed by a preliminary morphological phylogeny of monogenean
      genera from Cichlidae and other selected Monogenea genera, rendering the parasite
      distribution explicable under both vicariance and dispersal. Testable hypotheses
      are put forward in this parasitological approach to cichlid biogeography. Along
      with more comprehensive in-depth morphological phylogeny, comparison with
      molecular data, clarifying dactylogyridean evolution on different continents and
      from various fish families, and providing temporal information on host-parasite
      history, are needed to discriminate between the possible scenarios.

PMID- 21869938
TI  - 5 points on anterior cruciate ligament injuries in young athletes.

PMID- 21869939
TI  - Relationship between anthropometric measurements and hamstring autograft diameter
      in anterior cruciate ligament reconstruction.
AB  - The role of anthropometric measurements in the prediction of hamstring autograft
      size remains unclear. In this internal review board - approved study, we
      evaluated medical records for patients receiving anterior cruciate ligament (ACL)
      reconstruction with hamstring autograft at our institution between 2006 and 2008.
      One hundred and thirty-two patients received hamstring autografts. Correlation
      coefficients and step-wise multiple linear regression analysis were used to
      determine the relationships between sex, age, height, body mass index (BMI), and
      hamstring graft diameter. Women had significantly smaller grafts than men (P <
      .00001). Twenty-four patients had grafts less than 7 mm in diameter and 18 of
      those patients were female. Age and BMI did not correlate with graft diameter in
      women. Height correlated to graft diameter in women (P = .002, R(2) = 0.14).
      Women shorter than 65 in had significantly smaller graft diameters (mean [SD],
      6.94 [0.45] mm), than those women 65 in and taller (mean [SD], 7.20 0.49] mm; (P
      = .03). Age and height did not correlate with graft size in men. BMI greater than
      25 kg/m(2) correlated with larger graft diameter, but BMI less than 18 kg/m(2)
      did not predict graft sizes less than 7 mm. Therefore, alternative graft options
      should be considered in women less than 65 in tall.

PMID- 21869940
TI  - Posterior remodeling of medial clavicle causing superior vena cava impingement.
AB  - Injuries involving the sternoclavicular region resulting in posterior
      displacement of the medial clavicle are rare, and those that occur prior to
      fusion of the medial epiphyseal growth plate are more often a result of physis
      fracture, rather than sternoclavicular joint dislocation. Medial clavicular
      physis fractures initially are treated by closed reduction with the expectation
      of normal osseous repair and remodeling. We report a case of a previously
      fractured medial clavicle physis that abnormally remodeled, was reinjured, and
      resulted in posterior displacement with superior vena cava impingement and
      brachioplexopathy. Our case report describes the patient's initial injury and
      repair, the reinjury and discovery of abnormal remodeling, and the outcome of
      surgical intervention. We also include a review of recent literature on
      sternoclavicular joint injuries and treatment options. To our knowledge, this is
      the first reported case of an abnormally remodeled medial clavicle resulting in
      superior vena cava compression.

PMID- 21869941
TI  - Management of simultaneous ipsilateral dislocation of hip, knee, and ankle.

PMID- 21869942
TI  - Complications associated with use of anterior cruciate ligament fixation devices.
AB  - Fixation devices used during anterior cruciate ligament (ACL) reconstruction are
      of numerous designs and materials. Untoward events following the use of these
      devices are not common. However, if unrecognized, they can lead to serious
      complications. This article summarizes some of the reported complications with
      ACL fixation devices. There are complications common to all devices but others
      are unique to the implant itself or to the material of which it is made. Surgeons
      must be aware of the potential adverse events that can occur with the particular
      device being used.

PMID- 21869943
TI  - Fracture risk with pressurized-spray cryosurgery.
AB  - Forty-two patients treated with curettage, burring, direct pressurized
      cryotherapy, and bone grafting or cementation were retrospectively reviewed.
      There were no pathologic fractures in this study group, compared with a 17%
      fracture rate in recent studies using the "direct pour" technique. Direct
      pressurized cryotherapy was used in 3 separate freezing cycles in each case. This
      approach may significantly reduce the risk for fracture compared with historical
      controls using the direct-pour technique.

PMID- 21869944
TI  - Posterior cruciate ligament resection for ganglion cyst and associated ligament
      degeneration.
AB  - With increased use of magnetic resonance imaging (MRI) and arthroscopy, intra
      articular ganglion cysts of the posterior cruciate ligament (PCL) have received
      more recognition as a possible cause of knee discomfort. Reported treatment
      options have ranged from ultrasound-guided cyst aspiration to arthroscopic cyst
      resection. In this report, we present the case of a patient who, on MRI, was
      diagnosed with a symptomatic intrasubstance PCL ganglion that later, during
      surgery, demonstrated mucinous degeneration of the entire ligament. Treatment was
      complete resection of the PCL. Five years after surgery, the patient demonstrated
      excellent, asymptomatic knee function. Although the best treatment for an
      intrasubstance PCL ganglion cyst that has caused degeneration of the entire
      ligament is unknown, PCL resection without reconstruction should be considered a
      viable option. It can result in a large increase in range of motion and function.

PMID- 21869945
TI  - Tenosynovial giant cell tumor of the thigh: positron emission tomography
      findings.
AB  - Tenosynovial giant cell tumors (TGCTs) are pigmented villonodular proliferative
      lesions originating from the synovium, bursa, or joint. TGCTs tend to be locally
      aggressive, and there is a chance for multiple occurrences, which often lead to
      impairment of joint function. In this article, we report the case of a diffuse
      type extra-articular TGCT found in the thigh of a 36-year-old woman. Surveillance
      F-18 fluorodeoxyglucose positron emission tomography detected increased activity
      within the left thigh. This activity was confirmed with magnetic resonance
      imaging and with surgical excision and histopathologic determination of the
      tumor. This patient's case suggests that TGCTs may be discovered and followed
      after resection with positron emission tomography.

PMID- 21869946
TI  - The MRI geyser sign: acromioclavicular joint cysts in the setting of a chronic
      rotator cuff tear.
AB  - We present the case of a 71-year-old man with a large acromioclavicular (AC)
      joint cyst successfully managed with surgical excision. AC joint cysts are soft
      tissue masses generally signifying underlying rotator cuff pathology.
      Traditionally, these cysts were identified with shoulder arthrography as a
      "geyser" of fluid escaping through the AC joint. Magnetic resonance imaging (MRI)
      is today's preferred imaging modality; we describe the MRI equivalent of the
      "geyser sign," signifying synovial fluid escaping through the cuff defect, across
      the subacromial bursa, and decompressing superiorly through a degenerated AC
      joint. Surgical management is preferred for symptomatic cysts. Based on a review
      of limited retrospective case series, recommendations for management of these
      lesions are as follows. Repair of the rotator cuff is preferable whenever
      possible. In the case of an irreparable defect, good results can be achieved
      through excisional AC joint arthroplasty and resection of the cyst base.
      Aspiration of these cysts should not be attempted, due to the high recurrence
      rate and potential for a draining sinus. Hemiarthroplasty also may be effective
      in indirectly decompressing these cysts; but given the invasive nature of this
      procedure, it should be reserved for patients who are also symptomatic from cuff
      arthropathy.

PMID- 21869947
TI  - Outcome of intramedullary fixation of clavicular fractures.
AB  - We conducted a retrospective, single-center (tertiary referral center with
      associated level I trauma center) review to evaluate the outcome of open
      reduction and internal fixation (ORIF) with intramedullary (IM) clavicle pin of
      displaced clavicular fractures. Sixty-eight displaced midshaft clavicle fractures
      in 68 patients underwent ORIF with IM clavicle pins. Patients were identified
      through a perioperative database by searching for Current Procedural Terminology
      (CPT) codes. Union was the primary outcome. Secondary outcomes included time to
      union, pain, incidence of nonunion and delayed union, postoperative range of
      motion, and incidence of complications. Sixty-six fractures (97%) went on to
      union. Complications included painful hardware (44%), deep and superficial wound
      infections (10%), and hardware failure (4%), including pin breakage and
      extrusion. Postoperative shoulder pain was present in 10% of patients and limited
      shoulder range of motion in 12%. IM pin fixation can provide good outcomes, even
      for fractures with a significant amount of shortening and comminution.

PMID- 21869948
TI  - In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic
      algorithm techniques.
AB  - This study aimed to evaluate the clinical utility of applying near-infrared (NIR)
      Raman spectroscopy and genetic algorithm-partial least squares-discriminant
      analysis (GA-PLS-DA) to identify biomolecular changes of cervical tissues
      associated with dysplastic transformation during colposcopic examination. A total
      of 105 in vivo Raman spectra were measured from 57 cervical sites (35 normal and
      22 precancer sites) of 29 patients recruited, in which 65 spectra were from
      normal sites, while 40 spectra were from cervical precancerous lesions (i.e., 7
      low-grade CIN and 33 high-grade CIN). The GA feature selection technique
      incorporated with PLS was utilized to study the significant biochemical Raman
      bands for differentiation between normal and precancer cervical tissues. The GA
      PLS-DA algorithm with double cross-validation (dCV) identified seven
      diagnostically significant Raman bands in the ranges of 925-935, 979-999, 1080
      1090, 1240-1260, 1320-1340, 1400-1420, and 1625-1645 cm(-1) related to proteins,
      nucleic acids and lipids in tissue, and yielded a diagnostic accuracy of 82.9%
      (sensitivity of 72.5% (29/40) and specificity of 89.2% (58/65)) for precancer
      detection. The results of this exploratory study suggest that Raman spectroscopy
      in conjunction with GA-PLS-DA and dCV methods has the potential to provide
      clinically significant discrimination between normal and precancer cervical
      tissues at the molecular level.

PMID- 21869949
TI  - Viscosity of aqueous DNA solutions determined using dynamic light scattering.
AB  - Viscosity is a key parameter for characterising the behaviour of liquids and
      their flow. It is, however, difficult to measure precisely, reproducibly and
      accurately for aqueous solutions on a micro-litre volume scale, which is what is
      usually needed for biological samples. We report the development of a new method
      for measuring dynamic viscosity by measuring dynamic light scattering (DLS) data
      for a range of particles of well-defined size. Most applications of DLS involve
      determining particle size for samples of known viscosity. We inverted the usual
      protocol and endeavoured to determine viscosity for samples of known particle
      size. Viscosity measurements for water and aqueous solutions of calf thymus DNA
      made using DLS were compared with those from a U-tube viscometer. The styrene
      particles, frequently used as particle size standards, gave unsatisfactory
      results for our DNA samples as did C-6 derivatized silica and positively charged
      amino polystyrene microspheres. However, negatively charged carboxylate
      polystyrene microspheres particles readily gave accurate viscosity measurements
      over a range of temperatures (0-100  degrees C). The sample volume required
      depends on the cuvette used to measure DLS, but can be performed with samples
      sizes ranging from 40 to 3000 MUL. The sample can then be recovered for
      subsequent experiments. The DLS method is simple to perform at different
      temperatures and provides data of accuracy significantly above that of a U-tube
      viscometer. Our results also indicate a way forward to account accurately for
      solution viscosity in the normal applications of DLS to particle size
      determination by including the appropriate non-interacting particles as an
      internal standard.

PMID- 21869950
TI  - Bipolar electrode depletion: membraneless filtration of charged species using an
      electrogenerated electric field gradient.
AB  - We report a method for removing ions from aqueous solutions without the use of a
      membrane. The approach, which we call bipolar electrode depletion (BED), is based
      on the formation of an asymmetric electric field profile in a microchannel
      containing a bipolar electrode (BPE). The asymmetric field arises from local
      increases in conductivity caused by faradaic reactions at the BPE. We show how
      the asymmetric field can be used to deplete anions from a microchannel via a
      combination of electrophoresis and electroosmosis. We also apply this approach to
      filter an anionic species from a mixture of charged and neutral species being
      transported through a microchannel via electroosmosis. This technique could be
      utilized for desalination or filtration of any species possessing a net charge
      (e.g. heavy-metals, bacteria, proteins, or functionalized-nanoparticles).

PMID- 21869951
TI  - Determination of relative binding affinities of labeling molecules with amino
      acids by using scanning tunneling microscopy.
AB  - The binding behaviour of labeling molecule copper phthalocyanine tetrasulfonate
      sodium (PcCu(SO(3)Na)(4)) on the assemblies of representative polyamino acids has
      been studied by using scanning tunneling microscopy (STM). By directly
      visualizing the adsorption and distribution of the labeling species on the
      peptide assemblies in STM images, one could obtain relative binding affinities of
      the labeling molecule with different amino acid residues.

PMID- 21869952
TI  - A highly efficient silver niobium alumina catalyst for the selective catalytic
      reduction of NO by n-decane.
AB  - AgNb/Al(2)O(3) prepared by a nonhydrolytic sol-gel process is a highly efficient
      catalyst for NO(x) removal through selective catalytic reduction by hydrocarbons
      (HC-SCR). This result shows that the HC-SCR process remains a challenging method
      for lean engine DeNO(x).

PMID- 21869953
TI  - Modulating the self-assembly of rigid "clicked" dendrimers at the solid-liquid
      interface by tuning non-covalent interactions between side groups.
AB  - First generation poly(triazole-phenylene) dendrimers equipped with peripheral
      alkyl or carboxylic acid groups to engage in van der Waals and hydrogen-bonding
      interactions, respectively, assemble into distinct two-dimensional nano
      structures at the solid-liquid interface as revealed by high resolution STM
      investigations.

PMID- 21869954
TI  - An organogel formed from a cyclic beta-aminoalcohol.
AB  - A new organogelator with unique structural feature of a cyclic beta-aminoalcohol
      is presented as the first example of gelation by aminoalcohol through hydrogen
      bonding between hydroxy and amine.

PMID- 21869955
TI  - Extraction and isolation of shikimic acid from Ginkgo biloba leaves utilizing an
      ionic liquid that dissolves cellulose.
AB  - Shikimic acid, the starting material in the commercial synthesis of oseltamivir
      phosphate (Tamiflu(r)), was efficiently extracted and isolated from Ginkgo biloba
      leaves utilizing the ionic liquid 1-butyl-3-methylimidazolium chloride
      ([bmim]Cl), which dissolves cellulose.

PMID- 21869956
TI  - Synthesis of hybrid block copolymers via integrated ring-opening metathesis
      polymerization and polymerization of NCA.
AB  - Linear hybrid block copolymers with well controlled molecular weights and narrow
      polydispersities were synthesized via ring-opening metathesis polymerization
      (ROMP) followed by ring-opening polymerization of amino acid N-carboxyanhydrides.

PMID- 21869957
TI  - Cell-like systems with riboswitch controlled gene expression.
AB  - Synthetic riboswitches can be used to control protein expression under fully
      defined conditions in vitro, in water-in-oil emulsions, and in vesicles. The
      developed system could serve as a foundation for the construction of cellular
      mimics that respond to molecules of our choosing.

PMID- 21869958
TI  - Programmed placement of gold nanoparticles onto a slit-type DNA origami scaffold.
AB  - A novel DNA scaffold, called a DNA slit, was designed for the programmed
      positioning of Au nanoparticles (AuNPs), and various patterns of thiolated DNA
      slits were constructed. AuNPs were correctly placed at the predesigned positions
      in the thiolated DNA slits, indicating that the thiolated staples and the slit
      cavities guide the correct assembly of AuNPs.

PMID- 21869959
TI  - A design strategy for drug-like polyheterocycles with privileged substructures
      for discovery of specific small-molecule modulators.
AB  - We demonstrated the importance of maximized skeletal diversity of privileged
      substructures for the construction of a drug-like small-molecule library through
      a series of high-throughput screening and subsequent bioevaluations. Our
      divergent pDOS strategy can provide an efficient approach for the discovery of
      novel small-molecule modulators with excellent specificity.

PMID- 21869960
TI  - Diastereo- and enantioselective conjugate addition of alpha-substituted
      nitroacetates to maleimides under base-free neutral phase-transfer conditions.
AB  - Highly diastereo- and enantioselective conjugate addition of alpha-substituted
      nitroacetates to maleimides under base-free neutral phase-transfer conditions was
      developed for the synthesis of alpha,alpha-disubstituted alpha-amino acid
      derivatives.

PMID- 21869961
TI  - NbO lattice MOFs based on octahedral M(II) and ditopic pyridyl substituted
      diketonate ligands: structure, encapsulation and guest-driven luminescent
      property.
AB  - Two NbO-type MOFs based on ditopic pyridyl substituted diketonate ligands were
      reported. One exhibits a reversible SC-SC water encapsulation, while the other
      shows an interesting guest-driven luminescent property based on M(III)
      acetylacetonate (M = Eu and Fe) guest species.

PMID- 21869962
TI  - Measuring Si-C60 chemical forces via single molecule spectroscopy.
AB  - We measure the short-range chemical force between a silicon-terminated tip and
      individual adsorbed C(60) molecules using frequency modulation atomic force
      microscopy. The interaction with an adsorbed fullerene is sufficiently strong to
      drive significant atomic rearrangement of tip structures.

PMID- 21869963
TI  - Direct and mild palladium-catalyzed aerobic oxidative synthesis of imines from
      alcohols and amines under ambient conditions.
AB  - By ligand, TEMPO, and base screening, we developed a mild and green one-pot imine
      synthesis from alcohols and amines via a low-loading palladium-catalyzed tandem
      aerobic alcohol oxidation-dehydrative condensation reaction that can be readily
      carried out in open air at room temperature.

PMID- 21869964
TI  - On the magnetic channels in polymer membranes.
AB  - In recent years we have proposed magnetic membranes (membranes with dispersed
      granules of a permanent magnet) for the separation of oxygen and nitrogen in the
      air mixture. The idea was to utilize oxygen's paramagnetic properties which are
      absent in the nitrogen. The experimental results were promising but they demanded
      a theoretical description which is given in the present paper. By a detailed
      analysis of the available data we arrive at four important conclusions: (1)
      magnetic channels are formed around the magnetic granules, (2) the channels
      provide high permeability "highways" for the diffusion of permeating molecules,
      (3) the oxygen molecules, due to their paramagnetic properties, stick to these
      "highways" for a longer time than the nitrogen, which is probably based on the
      interaction with the Weiss molecular field of the permanent magnet, (4) the
      magnetic field induces aggregation between oxygen and nitrogen which enhances the
      transport of both nitrogen and oxygen by prolonging their residence in the
      channel. In addition to these findings, the most suggestive theory of magnetic
      membrane operation is ruled out: the forcing of the oxygen molecules due to the
      gradients of magnetic field generated by the granules is too weak to account for
      the observed effects.

PMID- 21869965
TI  - Surface versus volume effects in luminescent ceria nanocrystals synthesized by an
      oil-in-water microemulsion method.
AB  - Pure and europium (Eu(3+)) doped cerium dioxide (CeO(2)) nanocrystals have been
      synthesized by a novel oil-in-water microemulsion reaction method under soft
      conditions. In-situ X-ray diffraction and RAMAN spectroscopy, high-resolution
      transmission electron microscopy, UV/Vis diffuse-reflectance and Fourier
      transform infrared spectroscopy as well as time-resolved photoluminescence
      spectroscopy were used to characterize the nanaocrystals. The as-synthesized
      powders are nanocrystalline and have a narrow size distribution centered on 3 nm
      and high surface area of ~250 m(2) g(-1). Only a small fraction of the europium
      ions substitutes for the bulk, cubic Ce(4+) sites in the europium-doped ceria
      nanocrystals. Upon calcination up to 1000  degrees C, a remarkable high surface
      area of ~120 m(2) g(-1) is preserved whereas an enrichment of the surface Ce(4+)
      relative to Ce(3+) ions and relative strong europium emission with a lifetime of
      ~1.8 ms and FWHM as narrow as 10 cm(-1) are measured. Under excitation into the
      UV and visible spectral range, the europium doped ceria nanocrystals display a
      variable emission spanning the orange-red wavelengths. The tunable emission is
      explained by the heterogeneous distribution of the europium dopants within the
      ceria nanocrystals coupled with the progressive diffusion of the europium ions
      from the surface to the inner ceria sites and the selective participation of the
      ceria host to the emission sensitization. Effects of the bulk-doping and
      impregnation with europium on the ceria host structure and optical properties are
      also discussed.

PMID- 21869966
TI  - Homo- and heteronuclear alkali metal trimers formed on helium nanodroplets. Part
      I. Vibronic spectra simulations based on ab initio calculations.
AB  - We compare the 3(4)A(1) and 4(4)B(2) states of homonuclear and heteronuclear
      alkali trimers formed of potassium and rubidium. The Multireference Rayleigh
      Schrodinger Perturbation Theory of second order is applied to obtain the
      corresponding adiabatic potential energy surfaces. In the case of homonuclear
      trimers these pairs of states correspond to the two branches of the E?e Jahn
      Teller distorted 2(4)E' state. For heteronuclear trimers, the vibrational modes
      Q(x) and Q(y) are no longer degenerate, but the two electronic states still show
      a conical intersection at obtuse (KRb(2)) or acute (K(2)Rb) isosceles geometries.
      Spectroscopic consequences of this situation are discussed, vibronic spectra are
      predicted and compared to laser-induced fluorescence spectra obtained in helium
      droplet isolation spectroscopy experiments of our group.

PMID- 21869967
TI  - Homo- and heteronuclear alkali metal trimers formed on helium nanodroplets. Part
      II. Femtosecond spectroscopy and spectra assignments.
AB  - Homo- and heteronuclear alkali quartet trimers of type K(3-n)Rb(n) (n = 0,1,2,3)
      formed on helium nanodroplets are probed by one-color femtosecond (fs)
      photoionization (PI) spectroscopy. The obtained frequencies are assigned to
      vibrations in different electronic states in comparison to high level ab initio
      calculations of the involved potentials including pronounced Jahn-Teller and spin
      orbit couplings. Despite the fact that the resulting complex vibronic structure
      of the heavy alkali molecules complicates the comparison of experiment and theory
      we find good agreement for many of the observed lines for all species.

PMID- 21869968
TI  - Connecting theory with experiment to understand the initial nucleation steps of
      heteropolyoxometalate clusters.
AB  - A complimentary combination of Density Functional Theory (DFT) methodology and
      Electrospray Ionization-Mass Spectrometry (ESI-MS) has been utilized to increase
      our limited understanding of the first nucleation steps in the formation of the
      [XM(12)O(40)](n-) Keggin polyoxometalates (POMs) (where addenda metal atom M = W
      or Mo, and the heteroatom X = P or As). We postulate that the first key steps of
      nucleation into discrete, high nuclearity heteropolyanions proceed via the
      formation of isodinuclear species (e.g. [M(2)O(7)](2-)), which undergo successive
      steps of protonation and water condensation to form a heterotrinuclear fragment,
      which acts as a template for the constituent parts required for subsequent
      aggregation and formation of the plenary Keggin heteropolyanion. The stability of
      calculated structures of the numerous postulated intermediates has been analysed
      and discussed in detail, and these results complemented using experimental mass
      spectrometry, using an assembly (reaction solution analysis) and disassembly
      (fragmentation of single crystals) approach. Overall, no significant differences
      between the Keggin POMs were found when changing the addenda metal atom (W or Mo)
      or the heteroatom (P or As); although small differences among the lowest-energy
      structures were detected.

PMID- 21869969
TI  - Rydberg atom mediated polar molecule interactions: a tool for molecular-state
      conditional quantum gates and individual addressability.
AB  - We study the possibility to use interaction between a polar molecule in the
      ground electronic and vibrational state and a Rydberg atom to construct two-qubit
      gates between molecular qubits and to coherently control molecular states. A
      polar molecule within the electron orbit in a Rydberg atom can either shift the
      Rydberg state, or form a Rydberg molecule. Both the atomic shift and the Rydberg
      molecule states depend on the initial internal state of the polar molecule,
      resulting in molecular state dependent van der Waals or dipole-dipole interaction
      between Rydberg atoms. Rydberg atoms mediated interaction between polar molecules
      can be enhanced up to 10(3) times. We describe how the coupling between a polar
      molecule and a Rydberg atom can be applied to coherently control molecular
      states, and specifically, to individually address molecules in an optical
      lattice, and to non-destructively readout molecular qubits.

PMID- 21869970
TI  - Hemin interaction with bare and 4,4'-thio-bis-benzene-thiolate covered n-GaAs
      (110) electrodes.
AB  - Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS)
      investigations on the redox behavior of hemin at bare and 4,4'-thio-bis-benzene
      thiolate (TBBT) covered n-GaAs (110) electrodes in dimethylsulfoxide (DMSO)
      revealed the high irreversibility of the electroreduction process, which appeared
      to be closely related to the stable adsorbed species strongly interfering with
      the electronic properties of the semiconducting substrate. The subsequent
      exploration of the hemin-modified electrodes by second harmonic generation (SHG),
      X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM)
      measurements pointed to significant differences between the iron protoporphyrin
      species adsorbed on the bare- and TBBT-GaAs (110) electrodes. Only Fe(2+) species
      having a flat configuration with the porphyrin plane oriented parallel to the
      surface were detected on GaAs, unlike the TBBT-GaAs, where Fe(2+) and Fe(3+)
      species having both flat and vertical adsorption positions could be observed.
      These differences originate from the mutual interactions between the solvent,
      hemin and dithiolate molecules as well as their competition for the surface sites
      found to play a key role in the electrochemical process under discussion.

PMID- 21869971
TI  - Stabilization of chiral molecules by decoherence and environment interactions in
      the gas phase.
AB  - We study the tunnel dynamics of a chiral molecule between its left (L) and right
      (R) conformations, under the global effect of collisional decoherence together
      with the effect of a mean-field generated by the environment where an energetic
      difference, K, between homochiral and heterochiral interactions is assumed. We
      show that this decoherence leads unavoidably to equal populations of the L and R
      chiral conformations even for a high enough value of K which tends to keep
      localized an initial chiral state. However, we also show that K contributes to
      the stabilization of an initial L or R state for times that could be many orders
      of magnitude larger than the tunneling time, in the case the decoherence rate is
      much greater than the tunneling rate. In this case, an estimation of this
      stabilization time and a critical tunneling time is made. Even in the case in
      which the tunneling rate is greater than the decoherence rate, the effect of K is
      to keep localized the initial chiral state for times greater than the tunneling
      time. A possible slight chiral asymmetry is also considered.

PMID- 21869972
TI  - Lipid binding interactions of antimicrobial plant seed defence proteins:
      puroindoline-a and beta-purothionin.
AB  - The indolines and thionins are basic, amphiphilic and cysteine-rich proteins
      found in cereals; puroindoline-a (Pin-a) and beta-purothionin (beta-Pth) are
      members of these families in wheat (Triticum aestivum). Pin-a and beta-Pth have
      been suggested to play a significant role in seed defence against microbial
      pathogens, making the interaction of these proteins with model bacterial
      membranes an area of potential interest. We have examined the binding of these
      proteins to lipid monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'
      rac-glycerol) (DPPG) using a combination of neutron reflectometry, Brewster angle
      microscopy, and infrared spectroscopy. Results showed that both Pin-a and beta
      Pth interact strongly with condensed phase DPPG monolayers, but the degree of
      penetration was different. beta-Pth was shown to penetrate the lipid acyl chain
      region of the monolayer and remove lipids from the air/liquid interface during
      the adsorption process, suggesting this protein may be able to both form membrane
      spanning ion channels and remove membrane phospholipids in its lytic activity.
      Conversely, Pin-a was shown to interact mainly with the head-group region of the
      condensed phase DPPG monolayer and form a 33 A thick layer below the lipid film.
      The differences between the interfacial structures formed by these two proteins
      may be related to the differing composition of the Pin-a and beta-Pth hydrophobic
      regions.

PMID- 21869973
TI  - Multiply-charged ions and interstellar chemistry.
AB  - Gaseous molecules and ions, and even dust grains, can accumulate charge in the
      interstellar medium (ISM) by harvesting the energy of UV photons, cosmic rays,
      helium ions and metastable atoms. This Perspective views the various modes of gas
      phase formation of multiply-charged cations and the possible impact of their
      reactions on the chemical and ionization structure of the ISM, in the light of
      what is still very limited knowledge. Emphasis is given to gas-phase reactions of
      multiply-charged cations with atoms, molecules and electrons that lead to charge
      reduction, charge separation and chemical bond formation and these are examined
      for multiply-charged atoms, small molecules, hydrocarbons, polycyclic aromatic
      hydrocarbons and fullerenes, primarily as dications but also as a function of
      charge state. The increased electrostatic interaction due to multiple charge is
      seen to promote bonding to individual charge sites on large molecules (e.g.
      fullerenes) and allow ensuing "surface" chemistry under the influence of Coulomb
      repulsion. The unique ability of multiply charged cations to undergo charge
      separation reactions, either unimolecular or bimolecular, can feature in the
      production in the ISM of internally cold, but translationally hot, cations of
      lower charge state or hot atoms that may provide the driving force for subsequent
      chemical reactions in what is otherwise an ultracold environment. Available
      chemical kinetic models that account for the role of multiply-charged ions in the
      ISM are few and of limited scope and the observation of these ions in the ISM has
      remained elusive.

PMID- 21869974
TI  - Electro-oxidation of hydrazine at gold nanoparticle functionalised single walled
      carbon nanotube network ultramicroelectrodes.
AB  - Networks of pristine single walled carbon nanotubes (SWNTs) grown by catalysed
      chemical vapour deposition (cCVD) on an insulating surface and arranged in an
      ultramicroelectrode (UME) format are insensitive to the electro-oxidation of
      hydrazine (HZ) in aqueous solution, indicating a negligible metallic nanoparticle
      content. Sensitisation of the network towards HZ oxidation is promoted by the
      deliberate and controlled electrodeposition of "naked" gold (Au) nanoparticles
      (NPs). By controlling the deposition conditions (potential, time) it is possible
      to control the size and spacing of the Au NPs on the underlying SWNT network. Two
      different cases are considered: Au NPs at a number density of 250 +/- 13 NPs MUm(
      2) and height 24 nm +/- 5 (effective surface coverage, theta = 92%) and (ii) Au
      NPs of number density ~ 22 +/- 3 NPs MUm(-2) and height 43 nm +/- 8 nm (theta =
      35%). For both morphologies the HZ oxidation half-wave potential (E(1/2)) is
      shifted significantly negative by ca. 200 mV, compared to a gold disc UME of the
      same geometric area, indicating significantly more facile electron transfer
      kinetics. E(1/2) for HZ oxidation for the higher density Au NP-SWNT structure is
      shifted slightly more negative (by ~25 mV) than E(1/2) for the lower density Au
      NP electrode. This is attributed to the lower flux of HZ at NPs in the higher
      number density arrangement (smaller kinetic demand). Importantly, using this
      approach, the calculated HZ oxidation current density sensitivities for the Au NP
      SWNT electrodes reported here are higher than for many other metal NP
      functionalised carbon nanotube electrodes.

PMID- 21869975
TI  - Planarity takes over in the C(x)H(x)P(6-x) (x = 0-6) series at x = 4.
AB  - In this work we examine a structural transition from non-planar three-dimensional
      structures to planar benzene-like structures in the C(x)H(x)P(6-x) (x = 0-6)
      series. The global minima of P(6), CHP(5), and C(2)H(2)P(4) species are
      benzvalene-like structures. The benzvalene and benzene-like structures of
      C(3)H(3)P(3) are close in energy with the former being slightly more stable at
      our best level of theory. The transition occurs at x = 4 (C(4)H(4)P(2)), where
      the benzene-like structures become significantly more stable than the benzvalene
      like structures. We show that the pseudo Jahn-Teller effect, which is responsible
      for the deformation of planar P(6), CHP(5), and C(2)H(2)P(4) structures, is
      completely suppressed at x = 3 (benzene-like structures of C(3)H(3)P(3)). We
      present NICS(zz) values of all the benzene-like isomers in the series.

PMID- 21869976
TI  - Photophysical properties of ligand localized excited state in ruthenium(II)
      polypyridyl complexes: a combined effect of electron donor-acceptor ligand.
AB  - We have synthesized ruthenium(II) polypyridyl complexes (1) Ru(II)(bpy)(2)(L(1)),
      (2) Ru(II)(bpy)(2)(L(2)) and (3) Ru(II)(bpy)(L(1))(L(2)), where bpy = 2,2'
      bipyridyl, L(1) = 4-[2-(4'-methyl-2,2'-bipyridinyl-4-yl)vinyl]benzene-1,2-diol)
      and L(2) = 4-(N,N-dimethylamino-phenyl)-(2,2'-bipyridine) and investigated the
      intra-ligand charge transfer (ILCT) and ligand-ligand charge transfer (LLCT)
      states by optical absorption and emission studies. Our studies show that the
      presence of electron donating -NMe(2) functionality in L(2) and electron
      withdrawing catechol fragment in L(1) ligands of complex 3 introduces low energy
      LLCT excited states to aboriginal MLCT states. The superimposed LLCT and MLCT
      state produces redshift and broadening in the optical absorption spectra of
      complex 3 in comparison to complexes 1 and 2. The emission quantum yield of
      complex 3 is observed to be extremely low in comparison to that of complex 1 and
      2 at room temperature. This is attributed to quenching of the (3)MLCT state by
      the low-emissive (3)LLCT state. The emission due to ligand localized CT state
      (ILCT and LLCT) of complexes 2 and 3 is revealed at 77 K in the form of a new
      luminescence band which appeared in the 670-760 nm region. The LLCT excited state
      of complex 3 is populated either via direct photoexcitation in the LLCT
      absorption band (350-700 nm) or through internal conversion from the photoexcited
      (3)MLCT (400-600 nm) states. The internal conversion rate is determined by
      quenching of the (3)MLCT state in a time resolved emission study. The internal
      conversion to LLCT and ILCT excited states are observed to be as fast as ~200 ps
      and ~700 ps for complexes 3 and 2, respectively. The present study illustrates
      the photophysical property of the ligand localized excited state of newly
      synthesized heteroleptic ruthenium(II) polypyridyl complexes.

PMID- 21869977
TI  - N-heterocyclic amine-directed structures and properties of two Cu(II)
      diphosphonates.
AB  - By introducing the second organic N-heterocyclic ligands 4'-(4-pyridyl)
      4,2':6',4''-terpyridine (pyterpy) and 4,4'-bipyridyl (4,4'-bipy), two examples of
      Cu(II)-diphosphonates, [Cu(3)(HL)(2)(Hpyterpy)(2)].2H(2)O 1 and
      [Cu(4)(HL)(2)(4,4'-bipy)(H(2)O)(5)] 2 based on 1-hydroxyethylidenediphosphonic
      acid (H(5)L = CH(3)C(OH)(PO(3)H(2))(2)), have been hydrothermally obtained and
      characterized by powder X-ray diffraction, elemental analysis, IR, TG-DSC. The
      single-crystal X-ray diffractions reveal that compound 1 has a one-dimensional
      fishbone-like chain constructed by anions [Cu(3)(HL)(2)(2-)](n) while
      simultaneously organic cations [Hpyterpy(+)](n) suspending both sides, and
      compound 2 exhibits two-dimensional inorganic-organic alternate arrangement layer
      built from 1-D ladder-like inorganic chain with tetranuclear cluster [Cu(4)O(10)]
      via 4,4'-bipy linkage. The results of electrochemical measurements indicate half
      wave potential of 1 (E(1/2)(1) = 1.01 V) is less than that of 2 (E(1/2)(2) = 1.20
      V), indicating a good D-A system in ICT for 1. Moreover fluorescent measurements
      reveal that emission intensity of 1 centered at 422 nm is larger than that of 2
      emitted at 420 nm, caused by intraligand pi*-pi emission state of organic N
      heterocyclic amine (lambda(ex) = 233 nm). Magnetism data indicate that compound 1
      exhibits ferrimagnetic interactions between metal centers, while compound 2 has
      antiferromagnetic property.

PMID- 21869978
TI  - Role of local and electronic structural changes with partially anion substitution
      lithium manganese spinel oxides on their electrochemical properties: X-ray
      absorption spectroscopy study.
AB  - The electronic and local structures of partially anion-substituted lithium
      manganese spinel oxides as positive electrodes for lithium-ion batteries were
      investigated using X-ray absorption spectroscopy (XAS).
      LiMn(1.8)Li(0.1)Ni(0.1)O(4-eta)F(eta) (eta = 0, 0.018, 0.036, 0.055, 0.073,
      0.110, 0.180) were synthesized by the reaction between
      LiMn(1.8)Li(0.1)Ni(0.1)O(4) and NH(4)HF(2). The shift of the absorption edge
      energy in the XANES spectra represented the valence change of Mn ion with the
      substitution of the low valent cation as Li(+), Ni(2+), or F(-) anion. The local
      structural change at each compound with the amount of a Jahn-Teller Mn(3+) ion
      could be observed by EXAFS spectra. The discharge capacity of the tested
      electrode was in the order of LiMn(2)O(4) > LiMn(1.8)Li(0.1)Ni(0.1)O(4-eta)F(eta)
      (eta = 0.036) > LiMn(1.8)Li(0.1)Ni(0.1)O(4) while the cycleability was in the
      order of LiMn(1.8)Li(0.1)Ni(0.1)O(4-eta)F(eta) (eta = 0.036) ~
      LiMn(1.8)Li(0.1)Ni(0.1)O(4) > LiMn(2)O(4). It was clarified that
      LiMn(1.8)Li(0.1)Ni(0.1)O(4-eta)F(eta) has a good cycleability because of the
      anion doping effect and simultaneously shows acceptable rechargeable capacity
      because of the large amount of the Jahn-Teller Mn(3+) ions in the pristine
      material.

PMID- 21869979
TI  - New coordination polymers with extended arm cyclotriguaiacyclene ligands: 1D
      chains, and interpenetrating or polycatenating 2D (4(2).6(2))(4.6(2))2 networks.
AB  - A series of new 1D chain and 2D coordination polymers with cyclotriguaiacylene
      type ligands are reported. A zig-zag 1D coordination chain is found in complex
      [Cd(2)(4ph4py)(NO(3))(3)(H(2)O)(2)(DMA)(2)].(NO(3)).(DMA)(4), where 4ph4py =
      tris[4-(4-pyridyl)benzoyl]-cyclotriguaiacylene and DMA = dimethylacetamide, while
      complex [Zn(4ph4py)(2)(CF(3)COO)(H(2)O)].(CF(3)COO)(NMP)(7), where NMP = N
      methylpyrrolidone, has a doubly bridged coordination chain structure. Complexes
      [M(3ph3py)(NO(3))(2)].(NMP)(4) where M = Co or Zn, 3ph3py = tris[3-(3
      pyridyl)benzoyl]cyclotriguaiacylene, are isostructural and feature 1D ladder
      coordination chains. Complexes
      [Cd(2)(4ph4py)(2)(NO(3))(4)(NMP)].(NMP)(9)(H(2)O)(4) and
      [Co(4ph4py)(H(2)O)(2)].(NO(3))(2).(DMF)(2), where DMF = dimethylformamide, both
      have (3,4)-connected 2D coordination polymers with a rare (4(2).6(2))(4.6(2))(2)
      topology. A 2D coordination polymer with this topology is also found in complex
      [Co(2)(3ph4py)(2)(NO(3))(H(2)O)(5)].(NO(3))(3).(DMF)(9) where 3ph4py = tris[3-(4
      pyridyl)benzoyl]cyclotriguaiacylene. All 2D coordination polymer complexes are
      interpenetrating or polycatenating.
      [Co(2)(3ph4py)(2)(NO(3))(H(2)O)(5)](3+)polymers form a 2D->3D polycatenation
      showing self-complementary "hand-shake" interactions between the host-type
      ligands.

PMID- 21869980
TI  - Decorating the lanthanide terminus of self-assembled heterodinuclear
      lanthanum(III)/gallium(III) helicates.
AB  - Arylacylhydrazones of 2,3-dihydroxybenzaldehyde are appropriate ligands for the
      preparation of heterodinuclear triple-stranded helicates involving high
      coordinated lanthanide(III) ions. In the present study, three different kinds of
      substituents are introduced at the ligands in order to modify the organic
      periphery of the coordination compounds: (1) alkoxy groups are attached to the
      terminal phenyl groups, (2) NH protons of the hydrazones are substituted by
      phenyl moieties and (3) amino acid bearing units are attached to the terminus of
      the ligand. The new ligands nicely form the desired triple-stranded gallium(III)
      lanthanum(III) complexes [(5a-c,7,12,15)(3)GaLa] of which the highly phenylated
      derivative was crystallized and studied by X-ray diffraction.

PMID- 21869981
TI  - Clipping and stoppering anion templated synthesis of a [2]rotaxane host system.
AB  - A new [2]rotaxane host system containing nitro-isophthalamide macrocycle and
      polyether functionalised pyridinium axle components is prepared via clipping and
      stoppering synthetic methodologies using chloride anion templation. After
      removing the chloride anion template, (1)H NMR titration experiments reveal the
      unique interlocked host cavity to be highly selective for binding chloride and
      bromide in preference to basic oxoanions in competitive aqueous solvent mixtures.
      The rotaxane host system proved to be a superior anion complexant in comparison
      to the individual macrocycle and axle components. The anion binding affinity of
      the novel rotaxane is also investigated via molecular dynamics simulations and in
      general the structural data obtained corroborates the experimental solution anion
      recognition behaviour.

PMID- 21869982
TI  - Two novel inorganic-organic hybrid materials constructed from two kinds of
      octamolybdate clusters and flexible tetradentate ligands.
AB  - Two novel hybrid materials based on two kinds of octamolybdate anions and metal
      organic frameworks (MOFs), namely, [Ag(8)(L(1))(4)(alpha-Mo(8)O(26))(beta
      Mo(8)O(26))(H(2)O)(3)].H(2)O (1) and [Cu(I)(3.1)Cu(II)(0.5)(beta
      Mo(8)O(26))(0.5)(zeta-Mo(7)(VI)Mo(V)O(26))(0.5)(L(2))(2)(H(0.8)L(2))(0.5)] (2),
      where L(1) = 1,1'-(1,3-propanediyl)bis[2-(4-pyridyl)benzimidazole] and L(2) =
      1,1'-(1,4-butanediyl)bis[2-(3-pyridyl)benzimidazole], have been successfully
      synthesized. Crystal structure analysis revealed that 1 is a three-dimensional
      (3D) framework constructed of silver(I)-organic sheets and two types of
      (Mo(8)O(26))(4-) isomers. Compound 2 is a rare 3D framework containing
      copper(I,II)-organic cages and 1D channels occupied by the (zeta
      Mo(7)(VI)Mo(V)O(26))(5-) and (beta-Mo(8)O(26))(4-) anions. The two compounds were
      characterized by elemental analysis, IR spectroscopy, diffuse reflectivity
      spectroscopy, and photoluminescent spectroscopy. In addition, the photocatalytic
      behavior of 1 was investigated.

PMID- 21869983
TI  - A 3D alpha-Fe2O3 nanoflake urchin-like structure for electromagnetic wave
      absorption.
AB  - An alpha-Fe(2)O(3) nanoflake urchin-like structure is formed via the thermal
      oxidation of micrometre-sized iron spheres in air at temperatures of 300-400 
      degrees C. The material consists of alpha-Fe(2)O(3) nanoflakes grown
      perpendicularly to the sphere surface, a layer of a mixture of alpha-Fe(2)O(3)
      and Fe(3)O(4) as the oxidation shell, and an iron core. The ranges of the tip
      diameters of the nanoflakes are 20-30 nm (300  degrees C), 30-50 nm (350  degrees
      C), and 60-100 nm (400  degrees C). A composite consisting of the alpha-Fe(2)O(3)
      nanoflake urchin-like structure and an epoxy resin exhibits an excellent
      electromagnetic (EM) wave absorption ability. A small tip diameter (20-30 nm) and
      a high density (3 * 10(13) nanoflakes m(-2)) lead to a good network structure and
      good EM wave absorption. A minimum reflection loss (RL) of -33.8 dB (99.93% of EM
      wave absorption) at 7.8 GHz can be achieved using a 70 wt% urchin-like material
      as the filler in the resin matrix. In addition, a composite containing 60 wt%
      unchin-like material exhibits dual-frequency EM wave absorption. The peaks of the
      minimum RL values are located at 9.7 GHz (-26.2 dB) and 25.2 GHz (-21.0 dB). The
      unique morphology of the alpha-Fe(2)O(3) nanoflake urchin-like material is
      believed to be a key factor in the enhancement of the EM wave absorption.

PMID- 21869984
TI  - Environmental exposure to POPs and heavy metals in urban children from Dhaka,
      Bangladesh.
AB  - Persistent organic pollutants (POPs) and heavy metals are well known
      environmental pollutants. Even though numerous studies have been carried out to
      assess human exposures to these compounds, there is still a lack of data on
      humans from developing countries, especially in underprivileged children. The
      objective of this study was to assess the exposure to POPs and heavy metals in
      children from Dhaka, Bangladesh. One specific aim was to investigate whether
      children working at, or living close to, open waste disposal sites (WDSs) were
      more heavily exposed than other urban children. In 2008, blood and serum were
      collected from 73 children aged 7-16 from five neighbourhoods. Some of the
      children lived and worked at WDSs (N = 31), others lived next to a WDS (N = 17),
      whereas some children lived far from such sites (N = 25). Blood levels of lead (B
      Pb), cadmium (B-Cd), and selenium (B-Se) were determined by ICP-MS for all
      subjects. The metal levels were high, with B-Pb overall mean 120 MUg L(-1) (range
      40-220), B-Cd 0.74 MUg L(-1) (0.22-4.1), and B-Se 120 MUg L(-1) (81-170). There
      were no marked differences between children from the different neighbourhoods, or
      between WDS workers and other children. PCB levels were low and with no contrast
      between neighbourhoods, for CB-153 the overall mean was 7.0 ng g(-1) fat (2.8
      51). In contrast, high levels of DDTs were observed in all children, for 4,4'-DDE
      1300 ng g(-1) fat (420-4600), and for 4,4'-DDT 326 ng g(-1) fat (44-1400),
      indicating ongoing exposure. PBDE levels were low, and BDE-209 was quantitated
      mainly in children working at or living close to WDSs. In conclusion, the high
      levels of DDTs, lead and cadmium observed in children from Dhaka are of concern.
      Many children were exposed at levels where health effects have been observed, or
      at levels without safety margins.

PMID- 21869985
TI  - Pollution of soils with organophosphorus flame retardants and plasticizers.
AB  - The detection of the three organophosphate esters TCEP, TCPP and TBEP in soil
      samples indicates that pollution of soils from diffuse atmospheric sources has to
      be considered in risk assessments.

PMID- 21869986
TI  - Temperature imaging of water in a microchannel using thermal sensitivity of near
      infrared absorption.
AB  - This paper presents a remote and preparation-free method of temperature imaging
      of aqueous solutions in microchannels of microfluidic chips. The principle of
      this method is based on the temperature dependency of the near-infrared (NIR)
      absorption band (nu(2) + nu(3) band) of water. Temperature images were
      constructed from absorbances in a narrow wavelength range including 1908 nm, the
      most sensitive to temperature in the band, measured by using an NIR camera and an
      optical narrow-bandpass filter. Calculation and calibration results demonstrated
      a linear relationship between the absorption coefficient and temperature with a
      temperature coefficient of 1.5 * 10(-2) K(-1) mm(-1). Temperature images of 50
      MUm thick water in a Y-shaped PDMS microchannel locally heated by a neighboring
      hot wire were obtained, in which thermal diffusion processes in the microchip
      were visualized. Temperature resolution was estimated to be approximately 0.2 K
      according to the temperature coefficient and noise level.

PMID- 21869987
TI  - Temperature-controlled 'breathing' of carbon dioxide bubbles.
AB  - We report a microfluidic (MF) approach to studies of temperature mediated carbon
      dioxide (CO(2)) transfer between the gas and the liquid phases. Micrometre
      diameter CO(2) bubbles with a narrow size distribution were generated in an
      aqueous or organic liquid and subsequently were subjected to temperature changes
      in the downstream channel. In response to the cooling-heating-cooling cycle the
      bubbles underwent corresponding contraction-expansion-contraction transitions,
      which we term 'bubble breathing'. We examined temperature-controlled dissolution
      of CO(2) in four exemplary liquid systems: deionized water, a 0.7 M aqueous
      solution of NaCl, ocean water extracted from Bermuda coastal waters, and dimethyl
      ether of poly(ethylene glycol), a solvent used in industry for absorption of
      CO(2). The MF approach can be extended to studies of other gases with a distinct,
      temperature-dependent solubility in liquids.

PMID- 21869988
TI  - Demonstration of motionless Knudsen pump based micro-gas chromatography featuring
      micro-fabricated columns and on-column detectors.
AB  - This paper reports the investigation of a micro-gas chromatography (MUGC) system
      that utilizes an array of miniaturized motionless Knudsen pumps (KPs) as well as
      microfabricated separation columns and optical detectors. A prototype system was
      built to achieve a flow rate of 1 mL min(-1) and 0.26 mL min(-1) for helium and
      dry air, respectively, when they were used as carrier gas. This system was then
      employed to evaluate GC performance compromises and demonstrate the ability to
      separate and detect gas mixtures containing analytes of different volatilities
      and polarities. Furthermore, the use of pressure programming of the KP array was
      demonstrated to significantly shorten the analysis time while maintaining a high
      detection resolution. Using this method, we obtained a high resolution detection
      of 5 alkanes of different volatilities within 5 min. Finally, we successfully
      detected gas mixtures of various polarities using a tandem-column MUGC
      configuration by installing two on-column optical detectors to obtain
      complementary chromatograms.

PMID- 21869989
TI  - A digital microfluidic method for dried blood spot analysis.
AB  - Blood samples stored as dried blood spots (DBSs) are emerging as a useful
      sampling and storage vehicle for a wide range of applications. Unfortunately, the
      surging popularity of DBS samples has not yet been accompanied by an improvement
      in automated techniques for extraction and analysis. As a first step towards
      overcoming this challenge, we have developed a prototype microfluidic system for
      quantification of amino acids in dried blood spots, in which analytes are
      extracted, mixed with internal standards, derivatized, and reconstituted for
      analysis by (off-line and in-line) tandem mass spectrometry. The new method is
      fast, robust, precise, and most importantly, compatible with automation. We
      propose that the new method can potentially contribute to a new generation of
      analytical techniques for quantifying analytes in DBS samples for a wide range of
      applications.

PMID- 21869994
TI  - The C2H2 zinc finger transcription factors are likely targets for Ni(II)
      toxicity.
AB  - Ni(II) ions are able to hydrolyze Naa-(Ser/Thr) peptide bonds in Naa-(Ser/Thr)
      Xaa-His-Zaa sequences. We found that various human transcription factors contain
      such nickel hydrolytic patterns within C2H2 zinc finger (ZF) domains. We
      demonstrated the hydrolysis on two peptide models, the 3rd ZF of the Sp1
      transcription factor and the 1st ZF of the ZNF302 transcription factor. The
      experimentally studied reaction rates indicate that the hydrolysis reaction is
      likely to be an element of intracellular nickel toxicity.

PMID- 21869995
TI  - Role of metal ions in aggregation of intrinsically disordered proteins in
      neurodegenerative diseases.
AB  - Neurodegenerative diseases constitute a set of pathological conditions
      originating from the slow, irreversible, and systematic cell loss within the
      various regions of the brain and/or the spinal cord. Depending on the affected
      region, the outcomes of the neurodegeneration are very broad and diverse, ranging
      from the problems with movements to dementia. Some neurodegenerative diseases are
      associated with protein misfolding and aggregation. Many proteins that misfold in
      human neurodegenerative diseases are intrinsically disordered; i.e., they lack a
      stable tertiary and/or secondary structure under physiological conditions in
      vitro. These intrinsically disordered proteins (IDPs) functionally complement
      ordered proteins, being typically involved in regulation and signaling. There is
      accumulating evidence that altered metal homeostasis may be related to the
      progression of neurodegenerative diseases. This review examines the effects of
      metal ion binding on the aggregation pathways of IDPs found in neurodegenerative
      diseases.

PMID- 21869996
TI  - Nanopatterned graphene quantum dots as building blocks for quantum cellular
      automata.
AB  - Quantum cellular automata (QCA) is an innovative approach that incorporates
      quantum entities in classical computation processes. Binary information is
      encoded in different charge states of the QCA cells and transmitted by the inter
      cell Coulomb interaction. Despite the promise of QCA, however, it remains a
      challenge to identify suitable building blocks for the construction of QCA.
      Graphene has recently attracted considerable attention owing to its remarkable
      electronic properties. The planar structure makes it feasible to pattern the
      whole device architecture in one sheet, compatible with the existing electronics
      technology. Here, we demonstrate theoretically a new QCA architecture built upon
      nanopatterned graphene quantum dots (GQDs). Using the tight-binding model, we
      determine the phenomenological cell parameters and cell-cell response functions
      of the GQD-QCA to characterize its performance. Furthermore, a GQD-QCA
      architecture is designed to demonstrate the functionalities of a fundamental
      majority gate. Our results show great potential in manufacturing high-density
      ultrafast QCA devices from a single nanopatterned graphene sheet.

PMID- 21869997
TI  - Effect of metal nanoparticles decoration on electron field emission property of
      graphene sheets.
AB  - The electron field emission from metal nanoparticle decorated hydrogen exfoliated
      graphene (metal/HEG) occurs at low turn on and threshold fields due to its low
      work function and high field enhancement factor.

PMID- 21869998
TI  - Sinter-free phase conversion and scanning transmission electron microscopy of
      FePt nanoparticle monolayers.
AB  - Thermally robust monolayers of 4-6 nm diameter FePt nanoparticles (NPs) were
      fabricated by combining chemical synthesis and atomic layer deposition. Spin-cast
      monolayers of FePt NPs were coated with thin, 11 nm-thick layers of amorphous
      Al(2)O(3), followed by annealing to convert the FePt NPs from an alloy (A1) into
      intermetallic FePt (L1(0)) and FePt(3) (L1(2)) phases. The Al(2)O(3) layer serves
      as a barrier that prevents sintering between NPs during annealing at temperatures
      up to 730  degrees C. Electron and X-ray diffraction in conjunction with high
      angle annular dark-field scanning transmission electron microscopy (HAADF-STEM)
      show that as-synthesized A1 FePt NPs convert into L1(0) and L1(2) phase NPs
      through annealing. HAADF-STEM measurements of individual NPs reveal imperfect
      ordering and show that the NP composition determines which intermetallic phase is
      obtained. Mixed-phase NPs with L1(0) cores and FePt(3) L1(2) shells were also
      observed, as well as a smaller number of unconverted A1 NPs. These results
      highlight the need for improved control over the compositional uniformity of FePt
      NPs for their use in bit-patterned magnetic recording.

PMID- 21869999
TI  - Porous silicon nanowires.
AB  - In this mini-review, we summarize recent progress in the synthesis, properties
      and applications of a new type of one-dimensional nanostructures-single
      crystalline porous silicon nanowires. The growth of porous silicon nanowires
      starting from both p- and n-type Si wafers with a variety of dopant
      concentrations can be achieved through either one-step or two-step reactions. The
      mechanistic studies indicate the dopant concentration of Si wafers, oxidizer
      concentration, etching time and temperature can affect the morphology of the as
      etched silicon nanowires. The porous silicon nanowires are both optically and
      electronically active and have been explored for potential applications in
      diverse areas including photocatalysis, lithium ion batteries, gas sensors and
      drug delivery.

PMID- 21870000
TI  - Site-specific growth of Au particles on ZnO nanopyramids under ultraviolet
      illumination.
AB  - In this work, wurtzite ZnO nanocrystals with unique "pyramid" morphology were
      firstly prepared via solvothermal synthesis. It was determined that the ZnO
      nanopyramids are grown along the polar c-axis with the vertexes pointing to the
      [001] direction. When the mixture of ZnO nanopyramids and Au precursor (HAuCl(4))
      was exposed to ultraviolet (UV) illumination, Au particles were site-specifically
      formed on the vertexes of ZnO nanopyramids. The obtained Au/ZnO nanocomposite
      showed significantly enhanced photocatalytic activity as compared to the bare ZnO
      nanopyramids. First-principles based calculations well explained the formation of
      ZnO nanopyramids as well as the site-specific growth of Au, and revealed that
      during the photocatalysis process the Au particles can accommodate photoelectrons
      and thus facilitate the charge separation.

PMID- 21870001
TI  - Efficient synthesis of copillar[5]arenes and their host-guest properties with
      dibromoalkanes.
AB  - An efficient method for the synthesis of copillar[5]arenes was developed with
      FeCl(3) as catalyst and different 1,4-dialkoxybenzenes and paraformaldehyde as
      reactants (yields: 50-85%). The host-guest property of (co)pillar[5]arenes and
      terminal dibromoalkanes was investigated by (1)H NMR measurements and an X-ray
      study. The complexation behavior of the copillar[5]arenes can be tuned by
      changing the substituents on the host. A complete complexation selectivity was
      found between pillar[5]- and pillar[6]arenes, which is an interesting aspect for
      sensor techniques.

PMID- 21870002
TI  - Reactivity of p-nitrostyrene oxide as an alkylating agent. A kinetic approach to
      biomimetic conditions.
AB  - The alkylating potential of p-nitrostyrene oxide (pNSO)--a compound used as a
      substrate to study the activity of epoxide hydrolases as well as in polymer
      production and in the pharmaceutical industry--was investigated kinetically. The
      molecule 4-(p-nitrobenzyl)pyridine (NBP), as a model nucleophile for DNA bases,
      was used as an alkylation substrate. In order to gain insight into the effect of
      the hydrolysis of pNSO, as well as the hydrolysis of the NBP-pNSO adduct on the
      pNSO alkylating efficiency, these two competing reactions were studied in
      parallel with the main NBP-alkylation reaction. The following conclusions were
      drawn: (i) pNSO reacts through an S(N)2 mechanism, with NBP to form an adduct,
      pNSO-NBP (AD). The rate equation for the adduct formation is: r = d[AD]/dt =
      k(alk)[NBP][pNSO]-k(hyd)(AD) [AD] (k(alk), and k(hyd)(AD) being the alkylation
      rate constant and the NBP-pNSO adduct hydrolysis rate constant, respectively);
      (ii) the alkylating capacity of pNSO, defined as the fraction of initial
      alkylating agent that forms the adduct, is similar to that of mutagenic agents as
      effective as beta-propiolactone. The instability of the pNSO-NBP adduct formed
      could be invoked to explain the lower mutagenicity shown by pNSO; (iii) the
      different stabilities of the alpha and beta-adducts formed between NBP and
      styrene oxides show that the alkylating capacity f = k(alk)[NBP]/(k(alk)[NBP] +
      k(hyd)) (k(hyd) being the pNSO hydrolysis rate constant) as well as the
      alkylating effectiveness, AL = f/k(hyd)(AD), are useful tools for correlating the
      chemical reactivity and mutagenicity of styrene oxides; (iv) a pNSO-guanosine
      adduct was detected.

PMID- 21870003
TI  - 2-(2-Pyridyl) benzimidazole based Co(II) complex as an efficient fluorescent
      probe for trace level determination of aspartic and glutamic acid in aqueous
      solution: a displacement approach.
AB  - A weakly fluorescent cobalt(II) complex is synthesized using 2-(2-pyridyl)
      benzimidazole (PBI) as a chelating fluorescent ligand and characterized by single
      crystal X-ray structure. This complex serves as an efficient fluorescent probe
      for trace level determination of aspartic acid (AspA) and glutamic acid (GluA) in
      aqueous solution. Rest of the naturally occurring amino acids did not interfere.
      Both aspartic acid and glutamic acid replaces PBI from the coordination sphere of
      Co(II)-PBI complex resulting appearance of strong fluorescence signal for the
      released free PBI. The signal response is very fast and the interaction of both
      the AspA and GluA with the Co(II) is strong enough as evident from their
      displacement equilibrium constant values, viz. 4357.8 M(-1) and 8333.33 M(-1)
      respectively.

PMID- 21870004
TI  - Templating effects in aristolochene synthase catalysis: elimination versus
      cyclisation.
AB  - Analysis of the products generated by mutants of aristolochene synthase from P.
      roqueforti (PR-AS) revealed the prominent structural role played by the aliphatic
      residue Leu 108 in maintaining the productive conformation of farnesyl
      diphosphate to ensure C1-C10 (sigma-bond) ring-closure and hence (+)
      aristolochene production.

PMID- 21870005
TI  - Contrasting biscryptand/dimethyl paraquat [3]pseudorotaxanes: statistical vs.
      anticooperative complexation behavior.
AB  - Via the self-assembly of two bis(meta-phenylene)-32-crown-10-based cryptands,
      bearing covalent and metal complex (ferrocene) linkages, with dimethyl paraquat,
      novel [3]pseudorotaxanes were formed statistically and anticooperatively,
      respectively.

PMID- 21870012
TI  - Microfluidic platform for electrophysiological studies on Xenopus laevis oocytes
      under varying gravity levels.
AB  - Voltage clamp measurements reveal important insights into the activity of
      membrane ion channels. While conventional voltage clamp systems are available for
      laboratory studies, these instruments are generally unsuitable for more rugged
      operating environments. In this study, we present a non-invasive microfluidic
      voltage clamp system developed for the use under varying gravity levels. The core
      component is a multilayer microfluidic device that provides an immobilisation
      site for Xenopus laevis oocytes on an intermediate layer, and fluid and
      electrical connections from either side of the cell. The configuration that we
      term the asymmetrical transoocyte voltage clamp (ATOVC) also permits electrical
      access to the cytosol of the oocyte without physical introduction of electrodes
      by permeabilisation of a large region of the oocyte membrane so that a defined
      membrane patch can be voltage clamped. The constant low level air pressure
      applied to the oocyte ensures stable immobilisation, which is essential for
      keeping the leak resistance constant even under varying gravitational forces. The
      ease of oocyte mounting and immobilisation combined with the robustness and
      complete enclosure of the fluidics system allow the use of the ATOVC under
      extreme environmental conditions, without the need for intervention by a human
      operator. Results for oocytes over-expressing the epithelial sodium channel
      (ENaC) obtained under laboratory conditions as well as under conditions of micro-
      and hypergravity demonstrate the high reproducibility and stability of the ATOVC
      system under distinct mechanical scenarios.

PMID- 21870013
TI  - Atmospheric deposition of polybrominated dibenzo-p-dioxins and dibenzofurans in
      Guangzhou, China: seasonal variations and sources.
AB  - The atmospheric deposition of polybrominated dibenzo-p-dioxins and dibenzofurans
      (PBDD/Fs) was investigated at four locations in different suburban and urban
      functional districts of Guangzhou City. The annual deposition fluxes of total
      PBDD/Fs (eight 2,3,7,8-substituted tetra- to hexa-BDD/Fs) were in the range of 36
      51 (mean 46) pg m(-2) day(-1), and the corresponding TEQ fluxes were estimated to
      range between 7.9 and 11.3 (mean 10.3) pg I-TEQ m(-2) day(-1), indicating a
      noticeable pollution level. The deposition fluxes of PBDD/Fs during the wet
      season were 2-4 times as high as those during the dry season. Both rainfall and
      temperature positively correlated with PBDD/F deposition fluxes. Ambient
      gas/particle partition coefficients (K(p)) were predicted with SPARC. It appears
      seasonal variations of PBDD/F deposition fluxes were influenced by meteorological
      parameters and the local usage of brominated flame retardants (BFRs). The
      congener profiles of PBDD/Fs at four locations were similar either spatially or
      temporally, indicating that the main PBDD/F emission sources were similar to one
      another. Seasonal variations and congener patterns of PBDD/Fs indicated the
      possible sources included electronic waste recycling, industrial waste
      incinerators and products containing BFRs.

PMID- 21870014
TI  - Estimation of Model VII humic binding constants for Pd2+, Sn2+, U4+, NpO2(2+),
      Pu4+ and PuO2(2+).
AB  - Using previously established procedures that utilise linear free energy
      relationships, we estimated binding constants for the Windermere Humic Aqueous
      Model VII (WHAM/Model VII) for several radionuclide cations (Pd(2+), Sn(2+),
      U(4+), NpO(2)(2+), Pu(4+) and PuO(2)(2+)). This extends the number of cations
      that can be calculated with the model above the 40 included in the original Model
      VII work. When combined with equilibrium constants for inorganic species this
      allows the calculation of equilibrium distributions of chemical species under a
      wide range of conditions.

PMID- 21870015
TI  - An integrated passive micromixer-magnetic separation-capillary electrophoresis
      microdevice for rapid and multiplex pathogen detection at the single-cell level.
AB  - Here we report an integrated microdevice consisting of an efficient passive
      mixer, a magnetic separation chamber, and a capillary electrophoretic
      microchannel in which DNA barcode assay, target pathogen separation, and barcode
      DNA capillary electrophoretic analysis were performed sequentially within 30 min
      for multiplex pathogen detection at the single-cell level. The intestine-shaped
      serpentine 3D micromixer provides a high mixing rate to generate magnetic
      particle-pathogenic bacteria-DNA barcode labelled AuNP complexes quantitatively.
      After magnetic separation and purification of those complexes, the barcode DNA
      strands were released and analyzed by the microfluidic capillary electrophoresis
      within 5 min. The size of the barcode DNA strand was controlled depending on the
      target bacteria (Staphylococcus aureus, Escherichia coli O157:H7, and Salmonella
      typhimurium), and the different elution time of the barcode DNA peak in the
      electropherogram allows us to recognize the target pathogen with ease in the
      monoplex as well as in the multiplex analysis. In addition, the quantity of the
      DNA barcode strand (~10(4)) per AuNP is enough to be observed in the laser
      induced confocal fluorescence detector, thereby making single-cell analysis
      possible. This novel integrated microdevice enables us to perform rapid,
      sensitive, and multiplex pathogen detection with sample-in-answer-out capability
      to be applied for biosafety testing, environmental screening, and clinical
      trials.

PMID- 21870016
TI  - Mixed phosphine and group-13 metal ligator complexes [(PR3)(a)M(ECp*)b] (M = Mo,
      Ni; E = Ga, Al; R = C6H5, cyclo-C6H11, CH3).
AB  - Treatment of [Mo(N(2))(PMe(3))(5)] with two equivalents GaCp* (Cp* = eta(5)
      C(5)(CH(3))(5)) leads to the formation of cis-[Mo(GaCp*)(2)(PMe(3))(4)] (1),
      while AlCp* did not react with this precursor. In addition,
      [Ni(GaCp*)(2)(PPh(3))(2)] (2a), [Ni(AlCp*)(2)(PPh(3))(2)] (2b),
      [Ni(GaCp*)(2)(PCy(3))(2)] (3a), [Ni(GaCp*)(2)(PMe(3))(2)] (3b),
      [Ni(GaCp*)(3)(PCy(3))] (4) and [Ni(GaCp*)(PMe(3))(3)] (5) have been prepared in
      high yields by a direct synthesis from [Ni(COD)(2)] and stoichiometric amounts of
      the ligands PR(3) and ECp* (E = Al, Ga), respectively. All compounds have been
      fully characterized by (1)H, (13)C, and (31)P NMR spectroscopy, elemental
      analysis and single crystal X-ray diffraction studies.

PMID- 21870017
TI  - Fused perylenebisimide-carbazole: new ladder chromophores with enhanced third
      order nonlinear optical activities.
AB  - A series of ladder chromophores featuring planar structures of fused
      perylenebisimide and carbazole have been efficiently synthesized via
      photocyclization under sun light. Compared to N,N'-bis(3-pentyl) perylenebisimide
      (PBI-1), they show remarkably enhanced nonlinear properties.

PMID- 21870018
TI  - Host-guest sensing by calixarenes on the surfaces.
AB  - The present critical review reports on recent developments of optical
      nanoparticles based on the association of gold, silver, silica and quantum dots
      and calixarenes. These hybrid organic-inorganic compounds characterized by a
      thick organic layer self-assembled on the surface of a core of mineral surface
      atoms take advantage of the supramolecular recognition of luminescent calixarenes
      to fabricate nanodevices of nanoparticle size, capable of detecting metal
      cations, polyaromatic hydrocarbons and pesticides. Also presented is an
      explanation of the involvement of such nanoparticles in biochemical systems. This
      critical review provides an overview of their preparation, the manner in which
      they are characterized, and their use (108 references).

PMID- 21870019
TI  - Synthesis of 2,4,6-trisubstituted pyridines via an olefin cross-metathesis/Heck
      cyclisation-elimination sequence.
AB  - Heck reactions were performed on alpha,beta-unsaturated-delta-sulfonamido
      intermediates, derived from cross metathesis, to allow the instalment of
      substituents at the beta position. Subsequent one-pot cyclisation/elimination
      provides an operationally simple, catalytic and convergent synthesis of 2,4,6
      trisubstituted pyridines.

PMID- 21870020
TI  - Alzheimer's disease: clinical trials and the amyloid hypothesis.

PMID- 21870021
TI  - Cone beam computed tomography for vascular interventional radiology procedures:
      early experience.
AB  - INTRODUCTION: Cone beam computed tomography (CBCT) is a relatively new
      technological innovation that utilises fl at-panel detector technology to obtain
      CT-like images. The key strength of a CBCT system is that cross-sectional imaging
      can be obtained using the angiographic fl at panel unit without having to move
      the patient, allowing the radiologist to obtain soft tissue imaging during the
      procedure. This allows treatment planning, guidance, and assessment of outcome to
      be performed in one interventional suite. MATERIALS AND METHODS: From December
      2008 to June 2009, 24 CBCT scans were performed during vascular interventional
      procedures on our department's newly installed multi-axis fl at panel
      angiographic unit. RESULTS: Ten cases were performed for hepatic trans-arterial
      chemoembolisation, 9 cases for hepatic arterial Yttrium-90 infusion, while 5
      cases were for other indications. CBCT was found to be useful in 20 of the 24
      cases. CONCLUSION: Our early experience showed that CBCT was useful in impacting
      decisions during selected vascular interventional procedures. As CBCT technology
      improves, we can foresee wider applications of this technology.

PMID- 21870022
TI  - Second trimester prenatal screening for Down's syndrome in Mainland Chinese
      subjects using double-marker analysis of alpha-fetoprotein and beta-human
      chorionic gonadotropin combined with measurement of nuchal fold thickness.
AB  - INTRODUCTION: This study examines the effectiveness of double-marker analysis for
      alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) combined
      with measurement of nuchal fold thickness (NT) in the detection of Down's
      syndrome (DS) in Mainland Chinese subjects during second trimester prenatal
      screening. MATERIALS AND METHODS: We examined pregnant women with a singleton
      pregnancy between 15 and 21 weeks of gestation who underwent second trimester
      screening for DS using double-marker analysis for AFP and beta-hCG combined with
      ultrasound measurement of NT. The combined risk of DS was calculated. A cut-off
      of 1/270 was used to define a pregnancy at high-risk of DS. Amniocentesis was
      offered to all patients with high-risk pregnancies. RESULTS: Using double-marker
      analysis for AFP and beta-hCG in combination with measurement of NT, the
      detection rate of DS increased from 66.7% to 77.8% when compared with double
      marker analysis alone with similar false-positive rates (4.35%, 4.83%
      respectively). Using receiver operating characteristic curve (ROC) analysis, we
      determined that the double-marker analysis combined with measurement of NT
      exhibited an increased area under the curve (AUC) of 0.835 (95% CI: 0.743 to
      0.927) when compared to double-marker analysis alone, which had an AUC of 0.748
      (95% CI: 0.635 to 0.860). In addition, both methods were more effective than any
      other single test such as AFP, free beta-hCG or NT measurement. CONCLUSION:
      Second trimester prenatal screening using double-marker analysis for AFP and beta
      hCG combined with measurement of NT is effective for the detection of DS in
      Mainland Chinese pregnancies.

PMID- 21870023
TI  - Vascular endothelial growth factor C as a predictor of early recurrence and poor
      prognosis of resected stage I non-small cell lung cancer.
AB  - INTRODUCTION: Stage I non-small cell lung cancer (NSCLC) is potentially curable
      after completely resection, but early recurrence may infl uence prognosis. This
      study hypothesises that vascular endothelial growth factor C (VEGF-C) plays a key
      role in predicting early recurrence and poor survival of patients with stage I
      NSCLC. MATERIALS AND METHODS: The expression of VEGF-C was immuno-histochemically
      (IHC) analysed in tumour samples of primary stage I NSCLC and correlated to early
      recurrence (< 36 months), disease-free survival, and overall survival in all 49
      patients. RESULTS: Early recurrence was identifi ed in 16 patients (33%), and the
      early recurrence rate in strong and weak VEGF-C activity was significantly
      different (P = 0.016). VEGF-C was also an independent risk factor in predicting
      early recurrence (HR = 3.98, P = 0.02). Patients with strong VEGF-C staining also
      had poor 3-year disease-free survival (P = 0.008) and overall survival (P =
      0.007). CONCLUSION: Strong VEGF-C IHC staining could be a biomarker for
      predicting early recurrence and poor prognosis of resected stage I NSCLC, if the
      results of the present study are confirmed in a larger study. A more aggressive
      adjuvant therapy should be used in this group of patients.

PMID- 21870024
TI  - Refractory hypoxia in right ventricular infarction.

PMID- 21870025
TI  - Multi-system fibrosis and long-term use of ergotamine.

PMID- 21870026
TI  - Nodular extramedullary multiple myeloma: hepatic involvement presenting as
      hypervascular lesions on CT.

PMID- 21870027
TI  - Mesothelioma metastatisising to the sciatic nerve.

PMID- 21870028
TI  - Frontal lobe syndrome due to "A bunch of grapes".

PMID- 21870029
TI  - No temporal binding of action consequences to actions in a rhythmic context.
AB  - Temporal binding (TB) refers to a subjective contraction of the time that elapses
      between an action and a delayed sensory consequence of it. The TB effect has been
      demonstrated primarily in tasks in which a key press triggers a tone after a
      short delay and in which participants judge the timing of one or both of these
      events relative to a visual reference (e.g., a rotating clock hand). In the
      present Experiments 1 and 2, musicians listened instead to an auditory "clock" (a
      metronome) and occasionally made a tap that triggered a delayed tone. The task
      was to judge whether that test tone fell before, on, or after the midpoint of the
      interval between two metronome tones. In a passive control condition,
      participants judged test tones but did not tap. The hypothesis was that the test
      tone would be perceived as occurring earlier in the active than in the passive
      condition. However, there was no difference in perceptual judgments. Experiment 3
      used a visual metronome as the reference but again obtained negative results,
      despite greater uncertainty of judgments. It is suggested that TB of action
      consequences to actions does not occur when the reference signal is rhythmic
      because such a context enables participants (musicians, at least) to perceive and
      judge the actual time of occurrence of the action-triggered tone.

PMID- 21870030
TI  - Threat modeling for electronic health record systems.
AB  - The security of electronic health record (EHR) systems is crucial for their
      growing acceptance. There is a need for assurance that these records are securely
      protected from attacks. For a system as complex as an EHR system, the number of
      possible attacks is potentially very large. In this paper, a threat modeling
      methodology, known as attack tree, is employed to analyze attacks affecting EHR
      systems. The analysis is based on a proposed generic client-server model of EHR
      systems. The developed attack tree is discussed along with some system properties
      that enable quantitative and qualitative analysis. A list of suggested
      countermeasures are also highlighted.

PMID- 21870031
TI  - Design of the image-guided biopsy marking system for gastroscopy.
AB  - Endoscopists currently rely on an invasive biopsy tattooing method to identify
      previously biopsied sites. In order to better guide endoscopists to find the
      biopsy positions in follow-ups, we proposed a non-invasive image guided biopsy
      marking system for gastroscopy. Using an electromagnetic tracking device, the
      position of the gastroscope relative to the stomach was acquired and displayed in
      the guidance interface. The biopsy positions were recorded in computer for the
      use of guidance in follow-ups. The accuracy of the system was evaluated by both
      phantom experiments and in vivo experiments. The average target registration
      errors on the test animal and the volunteer are 13.4 mm and 11.2 mm respectively.
      Although the positioning error is slightly larger than current biopsy tattooing
      method, it satisfies the need for guidance. In the near future, we will validate
      the system by measuring how much it saves examination time.

PMID- 21870032
TI  - Anti-nociceptive and anti-inflammatory activities of (-)-alpha-bisabolol in
      rodents.
AB  - (-)-alpha-Bisabolol is an unsaturated, optically active sesquiterpene alcohol
      obtained by the direct distillation of essential oil from plants such as
      Vanillosmopsis erythropappa and Matricaria chamomilla. (-)-alpha-Bisabolol has
      generated considerable economic interest, as it possesses a delicate floral odour
      and has been shown to have antiseptic and gastroprotective activities. In this
      study, (-)-alpha-bisabolol was tested in standardised rodent models by gavage
      administration at doses of 100 and 200 mg/kg in the models of inflammation and 25
      and 50 mg/kg in the models of nociception. In the inflammatory models of paw
      oedema induced by carrageenan and dextran, the mice treated with (-)-alpha
      bisabolol showed smaller oedemas compared to animals treated only with the
      vehicle. (-)-alpha-Bisabolol was capable of reducing paw oedemas induced by 5-HT
      but not oedemas induced by histamine. (-)-alpha-Bisabolol demonstrated anti
      nociceptive activity in the models of visceral nociception induced by acetic acid
      and in the second phase of the nociception test induced by the intraplantar
      administration of formalin. (-)-alpha-Bisabolol did not have any effect in a
      thermal nociception model using a hot plate but was able to diminish mechanical
      inflammatory hypernociception evoked by carrageenan. These findings suggest that
      the anti-nociceptive action of (-)-alpha-bisabolol is not linked to a central
      mechanism but instead is related to the inflammatory process. (-)-alpha-Bisabolol
      was able to decrease leukocyte migration, protein extravasations and the amount
      of TNF-alpha to the peritoneal cavity in response to carrageenan. Additionally, (
      )-alpha-bisabolol reduced neutrophil degranulation in response to phorbol
      myristate-acetate. We demonstrate, for the first time, the peripheral anti
      inflammatory and anti-nociceptive activities of (-)-alpha-bisabolol.

PMID- 21870035
TI  - The challenge of profound hypoglycorrhachia: two cases of sarcoidosis and review
      of the literature.
AB  - We report two cases of sarcoidosis which were initially misdiagnosed due to
      profound hypoglycorrhachia. Sarcoidosis is a systemic inflammatory disorder which
      can mimick other entities and has a vast array of presentations including altered
      mentation and signs of increased intracranial pressure. Though hypoglycorrhachia
      has been described previously, these two cases are unique in not only the level
      of hypoglycorrhachia but also the diagnostic challenge presented. We propose that
      sarcoidosis should be in the differential of all cases of CNS diseases with any
      level of hypoglycorrhachia.

PMID- 21870036
TI  - Neonatal Behcet's disease without maternal history.
AB  - A neonate presented with frequent vomiting since 10 days old, followed by severe
      diarrhea. Multiple oral ulcers and recurrent genital ulcers subsequently
      appeared. Colonoscopy showed multiple shallow round ulcerations in the colon. The
      symptoms responded well to a short course of oral prednisolone. There was a brief
      recurrence of vomiting, diarrhea, and oral ulcers at 2 months old. The mother has
      never had any symptoms of Behcet's disease to date. This is the first reported
      case in literature of neonatal Behcet's disease without a maternal history of
      Behcet's disease, which raises doubts about the assumed role of maternal
      antibodies in the pathogenesis of neonatal Behcet's disease. A literature review
      of neonatal Behcet's disease shows that oral ulcers, skin lesions, fever, and
      leukocytosis are common features. However, only half of the patients fulfill the
      classical diagnostic criteria based on adult studies. A treatment consensus for
      neonatal cases is also lacking.

PMID- 21870037
TI  - Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment
      relevant to neurodegenerative disorders.
AB  - RATIONALE: Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa,
      possesses a large number of pharmacological effects including anticonvulsive,
      sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and
      neuroprotective, as demonstrated in clinical and preclinical studies. Many
      neurodegenerative disorders involve cognitive deficits, and this has led to
      interest in whether cannabidiol could be useful in the treatment of memory
      impairment associated to these diseases. OBJECTIVES: We used an animal model of
      cognitive impairment induced by iron overload in order to test the effects of
      cannabidiol in memory-impaired rats. METHODS: Rats received vehicle or iron at
      postnatal days 12-14. At the age of 2 months, they received an acute
      intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg)
      immediately after the training session of the novel object recognition task. In
      order to investigate the effects of chronic cannabidiol, iron-treated rats
      received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four
      hours after the last injection, they were submitted to object recognition
      training. Retention tests were performed 24 h after training. RESULTS: A single
      acute injection of cannabidiol at the highest dose was able to recover memory in
      iron-treated rats. Chronic cannabidiol improved recognition memory in iron
      treated rats. Acute or chronic cannabidiol does not affect memory in control
      rats. CONCLUSIONS: The present findings provide evidence suggesting the potential
      use of cannabidiol for the treatment of cognitive decline associated with
      neurodegenerative disorders. Further studies, including clinical trials, are
      warranted to determine the usefulness of cannabidiol in humans suffering from
      neurodegenerative disorders.

PMID- 21870038
TI  - The missing variable: ultrasonic vocalizations reveal hidden sensitization and
      tolerance-like effects during long-term cocaine administration.
AB  - RATIONALE: Subtypes of 50-kHz ultrasonic vocalizations (USVs) in rats are thought
      to reflect positive affect and occur with cocaine or amphetamine delivery. In
      contexts predicting forthcoming cocaine, pre-drug anticipatory USVs are initially
      minimal during daily sessions but gradually escalate over several weeks,
      presumably as the animal learns to expect and look forward to impending drug
      access. To gain more insight into motivational aspects of cocaine intake in
      animal models of drug dependence studies, it is important to compare experience
      dependent changes in lever response rate, USVs, and locomotion during cocaine
      conditioning and extinction trials. OBJECTIVE: To address whether cocaine-induced
      increases in lever responding and locomotor activity correspond with USV
      production. The study also determined whether short-term cocaine and context
      deprivation effects could be detected during conditioning or extinction. METHODS:
      Rats underwent 20 days of 60-min sessions of self- or yoked administration of
      cocaine (0.75 mg/kg/infusion, i.v.), followed by 19 days of extinction training
      (8 weeks total, weekends off). RESULTS: Lever responding for cocaine and cocaine
      induced locomotor activity increased across conditioning sessions. In contrast,
      the number of frequency modulated 50-kHz USVs evoked in response to cocaine
      infusion decreased with cocaine experience, suggesting perhaps tolerance to the
      rewarding properties of the drug. In addition, USVs but not lever pressing or
      locomotion are affected after brief periods of drug and/or drug context
      abstinence. CONCLUSIONS: Except for initial drug exposure, increased cocaine
      seeking during cocaine delivery could reflect either enhanced drug motivation or
      the development of drug tolerance, but not enhanced positive affect.

PMID- 21870039
TI  - Recurrent urinary tract infections in kidney transplant recipients.
AB  - Urinary tract infections (UTIs) are the most common infectious complication after
      kidney transplantation (KT). Recurrent UTIs after KT can contribute to increased
      morbidity and may also be associated with graft loss and mortality. Though
      several risk factors like female gender, diabetes mellitus, presence of ureteric
      stents, native kidney disease with urological malformations and re
      transplantation have been associated with recurrent UTIs after KT, vesicoureteric
      reflux appears to be a unique risk factor in this patient population. The
      emergence of drug-resistant pathogens as causative agents for post-transplant
      recurrent UTIs poses a significant therapeutic challenge. The use of pathogen
      specific antibiotic therapy guided by culture and sensitivity data is warranted.
      The optimal duration of antimicrobial therapy for recurrent UTIs in renal
      transplant recipients remains uncertain.

PMID- 21870040
TI  - Verbal, facial and autonomic responses to empathy-eliciting film clips by
      disruptive male adolescents with high versus low callous-unemotional traits.
AB  - This study examined empathy-related responding in male adolescents with
      disruptive behavior disorder (DBD), high or low on callous-unemotional (CU)
      traits. Facial electromyographic (EMG) and heart rate (HR) responses were
      monitored during exposure to empathy-inducing film clips portraying sadness,
      anger or happiness. Self-reports were assessed afterward. In agreement with
      expectations, DBD adolescents with high CU traits showed significantly lower
      levels of empathic sadness than healthy controls across all response systems.
      Between DBD subgroups significant differences emerged at the level of autonomic
      (not verbal or facial) reactions to sadness, with high CU respondents showing
      less HR change from baseline than low CU respondents. The study also examined
      basal patterns of autonomic function. Resting HR was not different between
      groups, but resting respiratory sinus arrhythmia (RSA) was significantly lower in
      DBD adolescents with high CU traits compared to controls. Results support the
      notion that CU traits designate a distinct subgroup of DBD individuals.

PMID- 21870041
TI  - MR first pass perfusion of benign and malignant cardiac tumours-significant
      differences and diagnostic accuracy.
AB  - OBJECTIVES: To determine the diagnostic value of magnetic resonance (MR) first
      pass perfusion in the differentiation of benign and malignant cardiac tumours.
      METHODS: 24 patients with cardiac tumours (11 malignant, histopathological
      correlation present in all cases) were examined using MRI. In addition to
      morphological sequences a saturation-recovery T1w-GRE technique was implemented
      for tumour perfusion. The maximum relative signal enhancement (RSE[%]) and the
      slope of the RSE(t)-curve (slopeRSE[%/s]) of tumour tissue were assessed. A t
      test was used to identify significant differences between benign and malignant
      tumours. Sensitivities and specificities were calculated for detection of
      malignant lesions and were compared with the sensitivity and specificity based on
      solely morphological image assessment. RESULTS: The RSE and slopeRSE of malignant
      cardiac tumours were significantly higher compared with benign lesions (p < 0.001
      and p < 0.001). The calculated sensitivities and specificities of RSE and
      slopeRSE for identification of malignant lesions were 100% and 84.6% and 100% and
      92.3%, respectively with cut-off values of 80% and 6%/s. The sensitivity and
      specificity for identification of malignant lesions on the basis of morphological
      imaging alone were 90.9% and 69.2%. CONCLUSIONS: With first pass perfusion,
      malignant cardiac masses can be identified with higher sensitivity and
      specificity compared with morphological image assessment alone.

PMID- 21870042
TI  - An urban perinatal health programme of strategies to improve perinatal health.
AB  - Promotion of a healthy pregnancy is a top priority of the health care policy in
      many European countries. Perinatal mortality is an important indicator of the
      success of this policy. Recently, it was shown that the Netherlands has
      relatively high perinatal death rates when compared to other European countries.
      This is in particular true for large cities where perinatal mortality rates are
      20-50% higher than elsewhere. Consequently in the Netherlands, there is heated
      debate on how to tackle these problems. Without the introduction of measures
      throughout the entire perinatal health care chain, pregnancy outcomes are
      difficult to improve. With the support of health care professionals, the City of
      Rotterdam and the Erasmus University Medical Centre have taken the initiative to
      develop an urban perinatal health programme called 'Ready for a Baby'. The main
      objective of this municipal 10-year programme is to improve perinatal health and
      to reduce perinatal mortality in all districts to at least the current national
      average of l0 per 1000. Key elements are the understanding of the mechanisms of
      the large health differences between women living in deprived and non-deprived
      urban areas. Risk guided care, orientation towards shared-care and improvement of
      collaborations between health care professionals shapes the interventions that
      are being developed. Major attention is given to the development of methods to
      improve risk-selection before and during pregnancy and methods to reach low
      educated and immigrant groups.

PMID- 21870043
TI  - Compatibility of garlic (Allium sativum L.) leaf agglutinin and Cry1Ac delta
      endotoxin for gene pyramiding.
AB  - delta-Endotoxins produced by Bacillus thuringiensis (Bt) have been used as bio
      pesticides for the control of lepidopteran insect pests. Garlic (Allium sativum
      L.) leaf agglutinin (ASAL), being toxic to several sap-sucking pests and some
      lepidopteran pests, may be a good candidate for pyramiding with delta-endotoxins
      in transgenic plants for enhancing the range of resistance to insect pests. Since
      ASAL shares the midgut receptors with Cry1Ac in Helicoverpa armigera, there is
      possibility of antagonism in their toxicity. Our study demonstrated that ASAL
      increased the toxicity of Cry1Ac against H. armigera while Cry1Ac did not alter
      the toxicity of ASAL against cotton aphids. The two toxins interacted and
      increased binding of each other to brush border membrane vesicle (BBMV) proteins
      and to the two important receptors, alkaline phosphatase (ALP) and aminopeptidase
      N (APN). The results indicated that the toxins had different binding sites on the
      ALP and APN but influenced mutual binding. We conclude that ASAL can be safely
      employed with Cry1Ac for developing transgenic crops for wider insect resistance.

PMID- 21870044
TI  - Genomic variations of Oenococcus oeni strains and the potential to impact on
      malolactic fermentation and aroma compounds in wine.
AB  - Malolactic fermentation (MLF) is the bacterially driven decarboxylation of L
      malic acid to L-lactic acid and carbon dioxide, and brings about deacidification,
      flavour modification and microbial stability of wine. The main objective of MLF
      is to decrease wine sourness by a small increase in wine pH via the metabolism of
      L-malic acid. Oenococcus oeni is the main lactic acid bacterium to conduct MLF in
      virtually all red wine and an increasing number of white and sparkling wine
      bases. Over the last decade, it is becoming increasingly recognized that O. oeni
      exhibits a diverse array of secondary metabolic activities during MLF which can
      modify the sensory properties of wine. These secondary activities include the
      metabolism of organic acids, carbohydrates, polysaccharides and amino acids, and
      numerous enzymes such as glycosidases, esterases and proteases, which generate
      volatile compounds well above their odour detection threshold. Phenotypic
      variation between O. oeni strains is central for producing different wine styles.
      Recent studies using array-based comparative genome hybridization and genome
      sequencing of three O. oeni strains have revealed the large genomic diversity
      within this species. This review will explore the links between O. oeni
      metabolism, genomic diversity and wine sensory attributes.

PMID- 21870045
TI  - Optimization of fermentation medium for triterpenoid production from Antrodia
      camphorata ATCC 200183 using artificial intelligence-based techniques.
AB  - In this study, alteration in morphology of submergedly cultured Antrodia
      camphorata ATCC 200183 including arthroconidia, mycelia, external and internal
      structures of pellets was investigated. Two optimization models namely response
      surface methodology (RSM) and artificial neural network (ANN) were built to
      optimize the inoculum size and medium components for intracellular triterpenoid
      production from A. camphorata. Root mean squares error, R (2), and standard error
      of prediction given by ANN model were 0.31%, 0.99%, and 0.63%, respectively,
      while RSM model gave 1.02%, 0.98%, and 2.08%, which indicated that fitness and
      prediction accuracy of ANN model was higher when compared to RSM model.
      Furthermore, using genetic algorithm (GA), the input space of ANN model was
      optimized, and maximum triterpenoid production of 62.84 mg l(-1) was obtained at
      the GA-optimized concentrations of arthroconidia (1.78 * 105 ml(-1)) and medium
      components (glucose, 25.25 g l(-1); peptone, 4.48 g l(-1); and soybean flour,
      2.74 g l(-1)). The triterpenoid production experimentally obtained using the ANN
      GA designed medium was 64.79 +/- 2.32 mg l(-1) which was in agreement with the
      predicted value. The same optimization process may be used to optimize many
      environmental and genetic factors such as temperature and agitation that can also
      affect the triterpenoid production from A. camphorata and to improve the
      production of bioactive metabolites from potent medicinal fungi by changing the
      fermentation parameters.

PMID- 21870046
TI  - Degradation of 2-chlorotoluene by Rhodococcus sp. OCT 10.
AB  - A strain Rhodococcus sp. OCT 10 DSM 45596(T), exhibiting 99.9% of 16S rDNA
      identity with Rhodococcus wratislaviensis NCIMB 13082, was isolated from a soil
      sample. The strain completely mineralised 2-chlorotoluene, 2-bromotoluene, o
      xylene, benzyl alcohol and benzoate. In contrast, 2-fluorotoluene was only
      partially mineralised. By GC-MS and (1)H-NMR analyses, 4-chloro-3-methylcatechol
      was identified as the central intermediate in the degradation pathway of 2
      chlorotoluene. It was further degraded by enzymes of the meta cleavage pathway.
      Catechol 1,2-dioxygenase and chlorocatechol 1,2-dioxygenase as the initial
      enzymes of the ortho cleavage pathways were not detectable under these
      conditions. Furthermore, neither formation nor oxidation of 2-chlorobenzylic
      alcohol, 2-chlorobenzaldehyde, or 2-chlorobenzoate was observed, thereby
      excluding side chain oxidation activity.

PMID- 21870047
TI  - Highly sensitive field test lateral flow immunodiagnostics of PVX infection.
AB  - A test system is described and expanded upon for mass field immunochromatography
      assay on porous membrane carriers for rapid diagnostics of potato virus X (PVX)
      in potato leaf tissue and sprout extracts using colloidal gold nanoparticles as a
      marker. Sensitivity of the assay developed for PVX identification is found to be
      comparable to the sensitivity of solid-phase sandwich-ELISA. Complete assay time
      does not exceed 15 min, and the lower limit of the PVX detection in non-clarified
      leaf extract is 2 ng/ml. A single measurement requires 0.1-0.2 ml (3-5 drops) of
      tested solution only (extracted from 10-20 mg of potato leaf tissue or sprouts).
      The simplicity and reliability of the method makes it especially efficient in
      direct rapid monitoring of many infected potato specimens in the field, as
      verified by field trials of 360 clones of 28 domestic and foreign cultivars of
      potato. A diagnostic kit for routine analyses of potato viral infections both in
      the laboratory and in the field is described and expanded upon.

PMID- 21870048
TI  - Bird fancier's lung: a state-of-the-art review.
AB  - Bird fancier's lung (BFL) resulting from avian antigen exposure is a very common
      form of hypersensitivity pneumonitis. Its pathogenesis is modified by genetic
      polymorphisms located within the major histocompatibility complex, and also by
      smoking, which may decrease serum antibody response to inhaled antigen. Acute,
      subacute, and chronic presentations of BFL are recognized, but often overlap
      clinically. Continued antigen exposure in the chronic phase portends a worse
      prognosis. Chronic bronchitis symptoms may be part of the BFL clinical spectrum,
      and rhinitis may suggest an allergic component. The diagnosis of BFL is enhanced
      by a high index of suspicion of exposure to avian antigen, recurrent symptomatic
      episodes occurring 4-8 h after exposure, inspiratory "velcro" crackles on
      auscultation, weight loss, and positive IgG precipitins to the antigen.
      Characteristic findings on high-resolution computed tomography of the chest
      include centrilobular nodules, ground-glass opacification, and mosaicism due to
      air trapping. Bronchoalveolar lavage will classically show >25% lymphocytosis, a
      CD4/CD8 ratio of <1.0 and >1% mast cells in the acute phase. Lung biopsies, if
      obtained in the subacute phase of the disease, typically show loosely formed
      granulomas, giant cells, a lymphoplasmacytic interstitial infiltrate, and
      possibly some degree of fibrosis. In some patients, usual interstitial pneumonia
      or fibrotic non-specific interstitial pneumonia patterns may be seen on surgical
      biopsy. Skin testing, serological testing, and bronchial provocation tests for
      BFL frequently suffer from a lack of standardization. Effective treatment for BFL
      consists mainly of antigen avoidance, as corticosteroids likely do not alter long
      term prognosis. Lung transplantation can be considered for progressive chronic
      disease refractory to medical measures.

PMID- 21870049
TI  - Prospective, multicenter, 3-year trial of laparoscopic adjustable gastric banding
      with the MIDBANDTM.
AB  - BACKGROUND: Although laparoscopic adjustable gastric banding (LAGB) is a popular
      metabolic/bariatric procedure, few prospective studies have assessed its
      outcomes. This study aimed to prospectively assess LAGB safety and effectiveness
      outcomes using the MIDBANDTM (MID, Dardilly, France). METHODS: Between May 2005
      and September 2006, 262 morbidly obese patients underwent primary gastric banding
      with pars flaccida technique in 13 French medical centers. Excess weight loss and
      change in body mass index (BMI, kilogram per square meter), percentage of
      patients with comorbidities, and obesity-related complications were recorded.
      Patients were followed at 6-month intervals for 3 years. A multivariable
      individual growth model was used to analyze weight change over time and determine
      potential predictors of weight loss. RESULTS: The majority of patients were
      female (n = 233, 89%), with mean age of 36.4 +/- 9.7 years. At 3 years, LAGB with
      MIDBAND resulted in significant decrease in mean BMI from 41.8 +/- 4.2 to 30.7 +/
      5.8 (p < 0.0001). Median excess weight loss and excess BMI loss were 61% and
      68%, respectively. The prevalence of obesity-related comorbidities had
      significantly decreased from 71% to 15% (p < 0.0001). Complications were observed
      in 26 patients (10%); device-related complications occurred in 20 patients
      (8.2%), requiring band removal in 8 (3.3%), and port revision in 8 (3.3%).
      Individual growth analysis identified significant predictors of weight loss
      including the number of follow-up visits. CONCLUSION: Prospective outcomes
      demonstrate the safety and efficacy of gastric banding over time using the
      MIDBAND. Individual growth modeling demonstrated that postoperative weight loss
      is strongly related to the frequency and consistency of follow-up visits.

PMID- 21870050
TI  - Is laparoscopic duodenojejunal bypass with sleeve an effective alternative to
      Roux en Y gastric bypass in morbidly obese patients: preliminary results of a
      randomized trial.
AB  - BACKGROUND: The incidence of obesity and related metabolic disorders in India and
      that of stomach carcinoma is one of the highest in the world. Hence, one requires
      a procedure that allows postoperative surveillance of the stomach with the best
      outcomes in terms of weight control and resolution of co-morbidities. Here, we
      compare one such procedure, duodenojejunal bypass with sleeve against the
      standard Roux-en Y gastric bypass. METHODS: Fifty-seven patients who were
      selected for a bypass procedure were randomized into two groups of laparoscopic
      duodenojejunal bypass with sleeve (DJB) and laparoscopic Roux en Y gastric
      bypass. The limb lengths were similar in both the groups, and the sleeve was done
      over a 36F bougie. RESULTS: The mean body mass index and percent excess weight
      loss at the end of 3, 6, and 12 months between the groups were not statistically
      significant. The operating times were higher in the DJB group. The rate of
      resolution of diabetes, hypertension, and dyslipidemias were also similar with no
      statistical significance. There was 100% resolution of dyslipidemias in both
      groups. There was one patient in the DJB group who presented with internal
      herniation 1 month post-op and was managed surgically. There was no mortality in
      both the groups. CONCLUSION: Laparoscopic duodenojejunal with sleeve gastrectomy,
      a procedure which combines the principles and advantages of sleeve gastrectomy
      and foregut hypothesis, is a safe and effective alternative to gastric bypass in
      weight reduction and resolution of co-morbidities especially for Asian countries.
      But, long-term follow-up is required.

PMID- 21870052
TI  - Effects of laparoscopic gastric band applications on plasma and fundic acylated
      ghrelin levels in morbidly obese patients.
AB  - BACKGROUND: It has been proposed that laparoscopic adjustable gastric banding
      (LAGB) procedure might play a role in modulation of fundic ghrelin production. To
      test this hypothesis, we examined plasma and tissue concentrations of acylated
      ghrelin in morbidly obese patients before and 6 months after LAGB. Baseline
      levels of acylated ghrelin in morbidly obese patients were also compared with
      those in age-matched, healthy, non-obese controls. METHODS: We studied 21
      patients who had been operated on for morbid obesity (M/F = 9/12, BMI = 49.3 +/-
      5.3 kg/m(2)) and 16 healthy, non-obese persons (M/F = 7/9, BMI = 23.0 +/- 1.7
      kg/m(2)). Fasting blood samples were collected once from the non-obese controls
      as well as the morbidly obese patients before and 6 months after the LAGB. The
      morbidly obese patients and their respective controls underwent gastroscopy for
      fundic biopsy. The plasma and fundic acylated ghrelin levels were evaluated in
      these groups by enzyme-linked immunosorbent assay. RESULTS: The plasma and fundic
      acylated ghrelin concentrations were significantly lower in obese patients than
      in non-obese controls (2.8 +/- 1.0 ng/ml, 727 +/- 171.7 ng/g tissue,
      respectively; p = 0.000). These parameters were significantly increased in
      morbidly obese patients 6 months after LAGB (4.1 +/- 1.2 ng/ml and p = 0.001; 999
      +/- 292.1 ng/g tissue and p = 0.003, respectively). CONCLUSIONS: We showed that
      fundic production of acylated ghrelin was significantly increased in morbidly
      obese patients 6 months after LAGB. Moreover, the weight loss after LAGB occurred
      in spite of the significant increase in the plasma and fundic acylated ghrelin
      levels. The potential role of ghrelin as being responsible for the weight loss
      after bariatric surgery needs to be elucidated in further studies.

PMID- 21870053
TI  - Clonality behind the increase of multidrug-resistance among non-invasive
      pneumococci in Southern Finland.
AB  - Multidrug-resistance among Streptococcus pneumoniae isolates, especially of
      serotype 19A, has increased in several countries recently. Even before the
      introduction of the pneumococcal conjugate vaccine into the Finnish National
      Vaccination Programme, the proportion of multidrug-resistant (MDR) pneumococci
      had doubled from 2007 to 2008, when it reached 3.6% in Southern Finland. Our aim
      was to look for a possible association between antimicrobial susceptibility and
      clonality among the MDR isolates. Twelve non-invasive isolates non-susceptible to
      penicillin, erythromycin, clindamycin, trimethoprim/sulfamethoxazole, and
      doxycycline from 2008 were available for serotyping, genotyping by multilocus
      sequence typing (MLST), and detection of genes encoding macrolide resistance and
      adherence-promoting pili. Two isolates were also resistant to ceftriaxone. Five
      serotypes, 19F, 19A, 6B, 23F, and 14, and six genotypes from three genetic
      lineages were found, among which CC320 was the largest. All isolates in this
      study carried the erm(B) macrolide resistance gene, and the CC320 isolates
      additionally carried the mef(A/E) macrolide resistance gene. Eleven isolates
      carried pilus islet 1, while the CC320 isolates also carried the pilus islet 2
      genes. The findings emphasize the importance of the careful monitoring of
      antimicrobial susceptibility and serotype distribution among pneumococci,
      especially now that antimicrobials and pneumococcal vaccines are in widespread
      use.

PMID- 21870054
TI  - Usefulness of consecutive biomarkers measurement in the management of community
      acquired pneumonia.
AB  - The aim of this study was to investigate whether procalcitonin (PCT), neopterin,
      C-reactive protein (CRP), and mid regional pro-atrial natriuretic peptide (MR
      proANP) levels at admission and during the clinical course can be useful for the
      management of patients with pneumonia. The study population consisted of 75
      patients with clinical and radiological diagnosis of pneumonia. Serum samples
      were collected at admission and during hospitalization. Complications were
      defined as intensive care unit (ICU) admission or death. The levels of PCT were
      significantly higher in pneumonia of definite bacterial origin in comparison to
      probable bacterial or unknown origin. The PCT levels were higher in pneumococcal
      pneumonia. The PCT and MR-proANP levels increased significantly according to the
      Pneumonia Severity Index (PSI). All biomarkers levels are higher in patients
      developing complications and who were dying. The serial levels of MR-proANP
      remain significantly elevated in patients developing complications and in
      patients classified in PSI and CURB-65 risk groups. In patients not developing
      complications, there is a significant decrease in the PCT levels. PCT can be
      useful for identifying pneumonia etiology. PCT and MR-proANP levels correlate
      with pneumonia severity rules. PCT and MR-proANP serial measurements can be
      useful for predicting short-term prognosis. Systemic biomarkers can provide
      additional information regarding clinical evolution, because these are dynamic
      and can be measured daily.

PMID- 21870055
TI  - In vivo key role of reactive oxygen species and NHE-1 activation in determining
      excessive cardiac hypertrophy.
AB  - Growing in vitro evidence suggests NHE-1, a known target for reactive oxygen
      species (ROS), as a key mediator in cardiac hypertrophy (CH). Moreover, NHE-1
      inhibition was shown effective in preventing CH and failure; so has been the case
      for AT1 receptor (AT1R) blockers. Previous experiments indicate that myocardial
      stretch promotes angiotensin II release and post-translational NHE-1 activation;
      however, in vivo data supporting this mechanism and its long-term consequences
      are scanty. In this work, we thought of providing in vivo evidence linking AT1R
      with ROS and NHE-1 activation in mediating CH. CH was induced in mice by TAC. A
      group of animals was treated with the AT1R blocker losartan. Cardiac
      contractility was assessed by echocardiography and pressure-volume loop
      hemodynamics. After 7 weeks, TAC increased left ventricular (LV) mass by ~45% vs.
      sham and deteriorated LV systolic function. CH was accompanied by activation of
      the redox-sensitive kinase p90(RSK) with the consequent increase in NHE-1
      phosphorylation. Losartan prevented p90(RSK) and NHE-1 phosphorylation,
      ameliorated CH and restored cardiac function despite decreased LV wall thickness
      and similar LV systolic pressures and diastolic dimensions (increased LV wall
      stress). In conclusion, AT1R blockade prevented excessive oxidative stress,
      p90(RSK) and NHE-1 phosphorylation, and decreased CH independently of hemodynamic
      changes. In addition, cardiac performance improved despite a higher work load.

PMID- 21870056
TI  - Ancient Chinese medicine and mechanistic evidence of acupuncture physiology.
AB  - Acupuncture has been widely used in China for three millennia as an art of
      healing. Yet, its physiology is not yet understood. The current interest in
      acupuncture started in 1971. Soon afterward, extensive research led to the
      concept of neural signaling with possible involvement of opioid peptides,
      glutamate, adenosine and identifying responsive parts in the central nervous
      system. In the last decade scientists began investigating the subject with
      anatomical and molecular imaging. It was found that mechanical movements of the
      needle, ignored in the past, appear to be central to the method and intracellular
      calcium ions may play a pivotal role. In this review, we trace the technique of
      clinical treatment from the first written record about 2,200 years ago to the
      modern time. The ancient texts have been used to introduce the concepts of yin,
      yang, qi, de qi, and meridians, the traditional foundation of acupuncture. We
      explore the sequence of the physiological process, from the turning of the
      needle, the mechanical wave activation of calcium ion channel to beta-endorphin
      secretion. By using modern terminology to re-interpret the ancient texts, we have
      found that the 2nd century B.C.:  physiologists were meticulous investigators and
      their explanation fits well with the mechanistic model derived from magnetic
      resonance imaging (MRI) and confocal microscopy. In conclusion, the ancient model
      appears to have withstood the test of time surprisingly well confirming the
      popular axiom that the old wine is better than the new.

PMID- 21870057
TI  - Regulation of target gene expression by the vitamin D receptor - an update on
      mechanisms.
AB  - Virtually all of the known biological actions of the hormonal ligand 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) are mediated by the vitamin D receptor
      (VDR). Following binding and activation by the ligand, the VDR localizes in the
      nucleus to the regulatory regions of target genes and recruits chromatin-active
      coregulatory complexes which, in turn, modulate transcriptional output. The
      failure of the VDR to function due to crippling mutations results in total
      hereditary resistance to 1,25(OH)(2)D(3) in both mice and humans. In this review,
      we summarize the structural and functional properties of the VDR and the role of
      1,25(OH)(2)D(3) in receptor activation, and then describe the results of recent
      studies using genome-wide analyses that define the overarching principles through
      which the VDR modulates genes expression. We also focus on the recent analysis of
      a specific 1,25(OH)(2)D(3) regulated gene that provides confirmation of the
      principles identified through these genome-wide methodologies. Taken together,
      these studies suggest an unanticipated increase in the complexity of the
      molecular processes that govern gene regulation by hormones and other factors.

PMID- 21870058
TI  - Correlation of SATB1 overexpression with the progression of human rectal cancer.
AB  - BACKGROUND AND AIMS: To date, the association between special AT-rich sequence
      binding protein 1 (SATB1) and colorectal cancer (CRC) has not been reported. This
      study was aimed at investigating the expression and potential role of SATB1 in
      human rectal cancers. METHODS: Ninety-three paired samples of rectal cancer and
      distant normal rectal tissue were analyzed by quantitative real-time PCR (qRT
      PCR) and immunohistochemistry (IHC), and the correlations between SATB1
      expression and clinicopathological parameters were evaluated. The expression
      profiles of SATB1 were also investigated in a panel of five human colon carcinoma
      cell lines. RESULTS: The general level of SATB1 mRNA in rectal cancer tissues was
      statistically significantly higher than that in normal mucosa (P = 0.043). The
      rate of positive SATB1 protein expression in rectal cancers (44.1%) was
      significantly higher than that in normal tissues (25.8%) by IHC analysis (P =
      0.009). Overexpression of SATB1 mRNA was more predominant in patients with
      earlier onset of rectal cancer (P = 0.033). SATB1 expression correlated with
      invasive depth and tumor node metastasis (TNM) stage at both protein and mRNA
      levels (P < 0.05). Furthermore, SATB1 expression in the poorly metastatic KM12C
      cells was significantly lower than the highly metastatic KM12SM and KM12L4A cells
      and higher than the HCT116 and SW480 cells (P = 0.001). These results were
      further confirmed by Western blotting. CONCLUSION: Our results indicate that
      SATB1 may play an important role in the progression of human rectal cancer, which
      represents a possible new mechanism underlying CRC.

PMID- 21870059
TI  - Resveratrol in the prevention and treatment of coronary artery disease.
AB  - Resveratrol is a polyphenolic compound found in red wine that is believed to be
      responsible for its beneficial cardiovascular effects. Extensive research in the
      past several decades has identified multiple mechanisms by which resveratrol
      modifies the cardiovascular risk factors that lead to coronary artery disease,
      yet translation to the clinical arena has been unexpectedly slow. In this
      article, we review the existing evidence regarding the beneficial effects of
      resveratrol and briefly discuss its potential therapeutic applications.

PMID- 21870060
TI  - Effects of dietary factors on lipoprotein-associated phospholipase A(2) (Lp-PLA
      (2)).
AB  - Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an enzyme which binds to
      oxidized LDL and has a pro-inflammatory role in the pathogenesis of
      atherosclerosis. The Lp-PLA(2) Studies Collaboration showed the relationship
      between Lp-PLA(2) levels and activity with coronary heart disease and ischemic
      stroke. Levels and activity of Lp-PLA(2) are reduced by statins. There have been
      limited studies focused on dietary factors and effects on LpPLA(2). A recent
      article from the Nurses' Health Study (HNS) and the Health Professionals Follow
      up Study (HPFS) has provided interesting insights. In this cross sectional study,
      a lower LpPLA(2) activity was found to be related to several dietary factors
      including higher percentage of energy consumed as protein instead of
      carbohydrate, mild to moderate intake of alcohol, higher mono-unsaturated fat
      intake instead of carbohydrate, and not being overweight. It is unknown whether
      changes in Lp-PLA(2) by diet alter cardiovascular risk.

PMID- 21870061
TI  - Brain MRI in neuromyelitis optica: what is its role?

PMID- 21870062
TI  - Gasterophilosis: a major cause of rectal prolapse in working donkeys in Ethiopia.
AB  - A retrospective study was conducted to investigate the cause of rectal prolapse
      in working donkeys in Ethiopia. Analysis of data on rectal prolapse cases
      obtained from the Donkey Health and Welfare Project clinic at the School of
      Veterinary Medicine, Addis Ababa University, from 1995 to 2004 revealed that
      83.6% (n = 177) of the cases were associated with Gasterophilus nasalis. The rest
      10.7% and 5.7% were associated with work-related (overloading) cause and
      diarrhoea, respectively. The mean and median numbers of G. nasalis recovered from
      the rectum of infected donkeys were 66 and 64, respectively, with a range of 2
      195. Over 100 G. nasalis larvae were recovered from the rectum of 22% of the
      donkeys. Circular demarcated ulcer-like and deep circumferential pits or ring
      like mucosal lesions were found at the larval attachment sites. G. nasalis
      infection and the associated rectal prolapse were observed year round. However,
      the intensity of rectal larval infection and incidence of rectal prolapse were
      significantly higher during the rainy season (P < 0.01). Age and sex of the
      donkeys had no significant effect on the intensity of rectal larval infection and
      incidence of rectal prolapse (P > 0.05).

PMID- 21870063
TI  - Effects of tea saponins on rumen microbiota, rumen fermentation, methane
      production and growth performance--a review.
AB  - Reducing methane emission from ruminant animals has implications not only for
      global environmental protection but also for efficient animal production. Tea
      saponins (TS) extracted from seeds, leaves or roots of tea plant are pentacyclic
      triterpenes. They have a lasting antiprotozoal effect, but little effect on the
      methanogen population in sheep. There was no significant correlation between the
      protozoa counts and methanogens. The TS decreased methanogen activity. It seems
      that TS influenced the activity of the methanogens indirectly via the depressed
      ciliate protozoal population. The TS addition decreased fungal population in the
      medium containing rumen liquor in in vitro fermentation, but no such effect was
      observed in the rumen liquor of sheep fed TS. Tea saponins had a minor effect on
      the pattern of rumen fermentation and hence on nutrient digestion. When added at
      3 g/day in diets, TS could improve daily weight gain and feed efficiency in
      goats. No positive associative effect existed between TS and disodium fumarate or
      soybean oil on methane suppression. Inclusion of TS in diets may be an effective
      way for improving feed efficiency in ruminants.

PMID- 21870064
TI  - Domestic livestock resources of Turkey: water buffalo.
AB  - Water buffalo are an ancient component of Turkey's domestic livestock resources.
      Commonly referred to as the Anatolian buffalo the animal is part of the
      Mediterranean group which includes Syrian, Egyptian and Southeast European
      animals. Once quite numerous, there have been drastic reductions in their numbers
      since the 1970s due to intensification of dairy activities, agricultural
      mechanization and changing consumer preferences. The main areas of distribution
      are in northwest Turkey in the Marmara and Black Sea Regions. Buffalo are kept in
      small herds by livestock and mixed crop-livestock farmers. Milk is the main
      product, meat is largely a by-product of the dairy function and provision of the
      once-important draught power is now a minor output. Buffalo milk is used to
      prepare a variety of speciality products but output of both milk and meat is very
      low in comparison to cattle. Conditions of welfare and health status are not
      optimal. Internal parasites are a constraint on productivity. Some buffalo are
      being used for conservation grazing in the Black Sea area to maintain optimal
      conditions for bird life in a nature reserve. Long neglected by government there
      are recent activities to establish conservation herds, set up in vitro banks and
      undertake molecular characterization. More effort is needed by government to
      promote buffalo production and to engage the general public in conservation of
      their national heritage.

PMID- 21870065
TI  - Helping cancer survivors return to work: what providers tell us about the
      challenges in assisting cancer patients with work questions.
AB  - INTRODUCTION: Cancer patients and survivors report receiving little work-related
      advice from healthcare providers about how to manage their work during treatment
      or when to return after completing primary treatment. This study explores the
      extent to which health professionals involved with colorectal cancer patients
      address work matters during active treatment. METHODS: Eighteen health
      professionals from oncology, occupational health and general practice were
      interviewed. Interviews were transcribed verbatim and analysed using thematic
      analysis. RESULTS: Health professionals provide conflicting and limited
      information to patients regarding ability to work during treatment, or when to
      return to work thereafter. Lack of knowledge about impacts of treatment and
      symptoms on work ability and sustainability, particularly in relation to
      different occupations and work tasks resulted in providers offering minimal
      guidance to patients. Current practices relied on providers' previous experiences
      with employed patients, rather than a sound evidence-base. CONCLUSIONS: The type
      of work-related information given to patients by providers is not systematic. It
      is necessary to develop a better knowledge base about the impacts of cancer and
      its treatment on work ability, sustainability and return to work that would help
      providers to offer more tailored advice to patients, consistently. Therefore, it
      is appropriate to recommend that formal training for providers is necessary.
      Enhancing the quality of information and training for health professionals to
      provide better work-related support to patients during the early stages of
      treatment could enable individuals to manage their work more effectively and
      facilitate a successful transition from patient to survivor.

PMID- 21870066
TI  - Fatal bilateral subdural haematoma after epidural anaesthesia for pregnancy.
AB  - CSF leak after epidural anaesthesia should be suspected after persistent
      headaches, which are worse on standing, suggestive of low pressure and CSF
      overdrainage. Subdural haemorrhage after CSF leak is a recognised complication;
      if suspected a CT Brain should be performed. An epidural blood-patch, and if
      necessary haematoma evacuation, can help prevent an unfortunate and tragic
      outcome.

PMID- 21870068
TI  - MRSA bacteraemia after caesarean section wound infection: when screening is
      missed and things go wrong.

PMID- 21870067
TI  - Role of hysteroscopy in the detection of endometrial pathologies in women
      presenting with postmenopausal bleeding and thickened endometrium.
AB  - OBJECTIVES: The goal of this study was to define the diagnostic value of
      hysteroscopy in evaluating uterine cavity compared to endometrial biopsy in women
      presenting with postmenopausal bleeding and thick endometrial mucosa with
      particular attention to endometrial hyperplasia and carcinoma. METHODS: Eighty
      three consecutive women presenting with postmenopausal bleeding and endometrial
      thickness of 5 mm or more measured by transvaginal ultrasound (TVU) were enrolled
      in a prospective study between May 2008 and July 2010. They underwent diagnostic
      hysteroscopy and endometrial biopsy. Hysteroscopic data was compared with the
      final diagnosis established by histological examination. RESULTS: The women's
      mean age was 61.2 +/- 5.2 years (range 44-80). The most frequent endometrial
      lesion was endometrial polyps (31.1%). Hyperplastic endometrium was confirmed in
      23 (27.8%), only 13 cases were suspected by the hysteroscope. Out of the 14
      (16.9%) proven cases of endometrial cancer, only half of the cases were
      suspected. In benign endometrial lesions, the sensitivity of the hysteroscopic
      view was 94.7%, specificity was 97.8%, positive (PPV) and negative (NPV)
      predictive values were 97.3 and 95.7%, respectively. On the other hand,
      hysteroscopy demonstrated an overall sensitivity, specificity, PPV, and NPV of
      56.5, 91.6, 72.2, and 84.6%, respectively, in endometrial hyperplasia, whereas
      the same parameters for endometrial cancer were 50, 94.2, 63.6, and 90.2%.
      CONCLUSION: Hysteroscopy can be used as the first line diagnostic tool for
      evaluating the benign endometrial lesions, such as endometrial polyp and
      submucosal myoma, nonetheless hysteroscopy has poor validity for excluding
      endometrial hyperplasia and cancer in women presenting with the postmenopausal
      bleeding and thick endometrium.

PMID- 21870069
TI  - Potential application of Raman spectroscopy for determining burial duration of
      skeletal remains.
AB  - Raman spectroscopy was used to study trends in chemical composition of bones in a
      burial environment. A turkey bone was sectioned and buried for short intervals
      between 12 and 62 days. Buried sections were analyzed using Raman
      microspectroscopy with 785 nm excitation. The results indicate that chemical
      changes in bone due to soil bacteria are time-dependent. Spectroscopic trends
      within buried bone segments were correlated to burial duration. A preliminary
      model was constructed using peak integration of Raman bands. Data collected
      within buried bone segments fit very well in this model. The model constructed is
      sensitive to changes in bone composition in a scale of days. This study
      illustrates the great potential of Raman spectroscopy as a non-destructive method
      for estimating the burial duration of bone for forensic purposes.

PMID- 21870070
TI  - Biliary excretion of essential trace elements in rats under oxidative stress
      caused by selenium deficiency.
AB  - The excretion of essential trace elements, namely, Se, Sr, As, Mn, Co, V, Fe, and
      Zn into the bile of Se-deficient (SeD) Wistar male rats was studied using the
      multitracer (MT) technique, and instrumental neutron activation analysis (INAA).
      Normal and Se-control (SeC) rat groups were used as reference groups to compare
      the effects of Se levels on the behaviors of the essential trace elements. The
      excretion (% dose) of Se, Sr, As, Mn, Co, and V increased with Se levels in the
      liver. The biliary excretion of Mn and As dramatically enhanced for SeC rats
      compared with SeD rats, while that of V accelerated a little for SeC rats. The
      radioactivity levels of (59)Fe and (65)Zn in the MT tracer solution were
      insufficient to measure their excretion into bile. The role of glutathione and
      bilirubin for biliary excretion of the metals was discussed in relation to Se
      levels in rat liver.

PMID- 21870071
TI  - Preparation and characterization of a molecularly imprinted polymer by grafting
      on silica supports: a selective sorbent for patulin toxin.
AB  - A new molecularly imprinted polymer (MIP) has been prepared on silica beads using
      the radical "grafting from" polymerization method for selective extraction of
      minor contaminant mycotoxin of patulin (PTL). After the introduction of amino
      groups onto the silica surface with 3-aminopropyltriethoxysilane, azo initiator
      onto the silica surface was achieved by the reaction of surface amino groups with
      4,4'-azobis(4-cyanopentanoic acid). The scale-up synthesis of MIP was then
      carried out in the presence of 6-hydroxynicotinic acid as template substitute,
      functional, and cross-linking monomers. The prepared sorbent was characterized
      using FT-IR spectroscopy, scanning electron microscopy, elemental analysis, and
      the adsorption-desorption selectivity, and the capacity characteristic of the
      polymer was investigated by a conventional batch adsorption test and Scatchard
      plot analysis. The results indicated that coated polymers had specific adsorption
      to PTL as compared with its co-occurring 5-hydroxymethyl-2-furaldehyde
      (hydroxymethylfurfural (HMF)), at the same bulk concentration for solution of PTL
      and HMF, the maximum absorbance in the solid-phase extraction (SPE) method to PTL
      were 93.97% or 0.654 MUg/mg while to HMF they were 76.89% or 0.496 MUg/mg.
      Scatchard analysis revealed that two classes of binding sites were formed in PTL
      MIP with dissociation constants of 3.2 * 10(-2) and 5.0 * 10(-3) mg/mL and the
      affinity binding sites of 8.029 and 1.364 mg/g, respectively. The recoveries of
      PTL were more than 90% for the developed MISPE and around 75% for the traditional
      liquid-liquid extraction in spiked apple juice samples. It was concluded that the
      method is suitable for the scale-up synthesis of PTL-MIP grafted on silica, and
      the polymer can be effectively applied as SPE coupled with high-performance
      liquid chromatography (HPLC) for the determination of PTL in apple juice or other
      related products.

PMID- 21870072
TI  - The possible role of esRAGE and sRAGE in the natural history of diabetic
      nephropathy in childhood.
AB  - The advanced glycation end products/receptor for advanced glycation end products
      (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We
      evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64
      pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and
      compared the values with those of 62 controls matched for age, gender and Tanner
      pubertal stages. We also explored the possible association of their
      concentrations with early signs of diabetic nephropathy, defined as changes in
      kidney volume and estimated glomerular filtration rate (eGFR). Significantly
      lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p
      = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type
      1 diabetes than in the controls. In both groups of patients with type 1 diabetes,
      the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of
      kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p =
      0.002) were higher than those of the controls. The regression analysis showed an
      inverse relationship between esRAGE and body surface-adjusted mean kidney volume
      (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in
      normoalbuminuric youths with type 1 diabetes than in their healthy peers. The
      inverse association between esRAGE levels and early kidney alterations suggests a
      potential role of esRAGE in diabetic nephropathy.

PMID- 21870074
TI  - Photophysical properties of novel picrate derivatives--solvent effect.
AB  - H and (13)C NMR spectra were recorded for some novel picrate derivatives derived
      from 3,3-dimethyl-2,6-diarylpiperidin-4-ones and 3-benzyl-2,6-diarylpiperidin-4
      one. The photophysical properties of the picrate derivatives were studied in
      several solvents, which include a wide range of apolar, polar and protic media.
      The observed lower fluorescence quantum yield may be due to an increase in the
      non-radiative deactivation rate constant. This is attributed due to the presence
      of increased electrostatic interaction between N-protonated piperidone ring and
      picryl anion ring so that the picryl anion ring lies perpendicular to the plane
      of the N-protonated piperidone ring i.e., non co-planarity. Such a geometrical
      change in the excited state leads to an important Stokes shift, reducing the
      reabsorption and reemission effects in the detected emission in highly
      concentrated solutions. The higher fluorescence quantum yield of the picrate
      derivatives are observed in polar media.

PMID- 21870073
TI  - A synthetic decursin analog with increased in vivo stability suppresses androgen
      receptor signaling in vitro and in vivo.
AB  - Targeting androgen receptor (AR) signaling with agents distinct from current
      antagonist drugs remains a rational approach to the prevention and treatment of
      prostate cancer (PCa). Our previous studies have shown that decursin and isomer
      decursinol angelate (DA), isolated from the Korean medicinal herb Angelica gigas
      Nakai, interrupt AR signaling and possess anti-PCa activities in vitro. In the
      LNCaP PCa cell model, these pyranoccoumarin compounds exhibit properties distinct
      from currently used antagonists (e.g., Casodex). However, both are rapidly de
      esterified to decursinol, a partial AR agonist. We report here that a synthetic
      decursin analog, decursinol phenylthiocarbamate (DPTC), has greater in vivo
      stability than the parent compounds. DPTC-decursinol conversion was undetectable
      in mice. Furthermore, in LNCaP cells, DPTC decreased prostate specific antigen
      (PSA) expression, down-regulated AR abundance and mRNA and inhibited AR nuclear
      translocation. The effect of DPTC on AR and PSA mRNA and protein abundance was
      also observed in VCaP cells expressing wild type AR. DPTC inhibited growth of
      both PCa cell lines through G(1) cell cycle arrest and apoptosis, as did decursin
      and DA. Furthermore, i.p. administration of DPTC for 3 weeks suppressed the
      expression of AR target genes probasin and Nkx3.1 in mouse prostate glands.
      Overall, our data suggest that DPTC represents a prototype lead compound for
      development of in vivo stable and active novel decursin analogs for the
      prevention or therapy of PCa.

PMID- 21870075
TI  - A pyrene-based highly selective turn-on fluorescent sensor for copper(II) ion and
      its application in live cell imaging.
AB  - A new pyrene derivative (chemosensor 1) containing a picolinohydrazide moiety
      exhibits high selectivity for Cu(2+) ion detection in mixed aqueous media
      (CH(3)OH:H(2)O = 7:3). Significant fluorescence enhancement was observed with
      chemosensor 1 in the presence of Cu(2+). However, the metal ions Ag(+), Ca(2+),
      Cd(2+), Co(2+), Cu(2+), Fe(2+), Fe(3+), Hg(2+), K(+), Mg(2+), Mn(2+), Ni(2+),
      Pb(2+), and Zn(2+) produced only minor changes in fluorescence for the system.
      The apparent association constant (K(a)) of Cu(2+) binding in chemosensor 1 was
      found to be 2.75*10(3) M(-1). The maximum fluorescence enhancement caused by
      Cu(2+) binding in chemosensor 1 was observed over the pH range 5-8. Moreover, by
      means of fluorescence microscopy experiments, it is demonstrated that 1 can be
      used as a fluorescent probe for detecting Cu(2+) in living cells.

PMID- 21870077
TI  - Evaluation of the World Health Organization criteria for chest radiographs for
      pneumonia diagnosis in children.
AB  - Our objective was to compare the inter-observer level of agreement in diagnosing
      pneumonia using the World Health Organization (WHO) guidelines for the
      interpretation of radiographs. We conducted a prospective study in a pediatric
      emergency room. Fifteen observers (13 pediatricians, 2 radiologists) interpreted
      200 pediatric (<5 years old) chest radiographs using the WHO guidelines.
      Observers were blinded to the clinical presentation. RESULTS were analyzed for
      kappa values. Individual readings were compared to two "gold standard" teams: (1)
      radiologist and pediatrician and (2) two radiologists. RESULTS: Alveolar
      pneumonia, non-alveolar pneumonia, and no pneumonia were found (by radiologists)
      in 12.8%, 2.7%, and 78.6% of readings, respectively. The mean kappa values for
      alveolar pneumonia, non-alveolar pneumonia, and no pneumonia of observers versus
      the team consisting of a radiologist and a pediatrician were 0.73, 0.23, and
      0.61, respectively. For non-alveolar pneumonia, the mean kappa value was higher
      for the gold standard consisting of a radiologist and a pediatrician when
      compared to the two-radiologist team. Pediatricians overdiagnosed "non-alveolar
      pneumonia" compared with radiologists. In contrast, for the alveolar pneumonia
      and no-pneumonia diagnoses, no significant differences were found. CONCLUSIONS:
      The WHO guidelines for interpretation of chest radiographs result in high level
      of agreement between readers for the definition of "alveolar pneumonia" and "no
      pneumonia" but poor agreement for non-alveolar pneumonia. The disagreement with
      regard to the latter was associated with overdiagnosis by pediatricians, which
      may lead to overtreatment. We believe that radiographic non-alveolar pneumonia
      should not be an endpoint for clinical trials and research, nor should it be
      implemented in clinical setting.

PMID- 21870076
TI  - Clozapine protects dopaminergic neurons from inflammation-induced damage by
      inhibiting microglial overactivation.
AB  - Increasing evidence suggests a possible involvement of neuroinflammation in some
      psychiatric disorders, and also pharmacological reports indicate that anti
      inflammatory effects are associated with therapeutic actions of psychoactive
      drugs, such as anti-depressants and antipsychotics. The purpose of this study was
      to explore whether clozapine, a widely used antipsychotic drugs, displays anti
      inflammatory and neuroprotective effects. Using primary cortical and
      mesencephalic neuron-glia cultures, we found that clozapine was protective
      against inflammation-related neurodegeneration induced by lipopolysaccharide
      (LPS). Pretreatment of cortical or mesencephalic neuron-glia cultures with
      clozapine (0.1 or 1 MUM) for 24 h attenuated LPS-induced neurotoxicity. Clozapine
      also protected neurons against 1-methyl-4-phenylpyridinium(+) (MPP(+))-induced
      neurotoxicity, but only in cultures containing microglia, indicating an
      indispensable role of microglia in clozapine-afforded neuroprotection. Further
      observation revealed attenuated LPS-induced microglial activation in primary
      neuron-glia cultures and in HAPI microglial cell line with clozapine
      pretreatment. Clozapine ameliorated the production of microglia-derived
      superoxide and intracellular reactive oxygen species (ROS), as well as the
      production of nitric oxide and TNF-alpha following LPS. In addition, the
      protective effect of clozapine was not observed in neuron-glia cultures from mice
      lacking functional NADPH oxidase (PHOX), a key enzyme for superoxide production
      in immune cells. Further mechanistic studies demonstrated that clozapine
      pretreatment inhibited LPS-induced translocation of cytosolic subunit p47(phox)
      to the membrane in microglia, which was most likely through inhibiting the
      phosphoinositide 3-kinase (PI3K) pathway. Taken together, this study demonstrates
      that clozapine exerts neuroprotective effect via the attenuation of microglia
      activation through inhibition of PHOX-generated ROS production and suggests
      potential use of antipsychotic drugs for neuroprotection.

PMID- 21870078
TI  - Clinicopathological findings of immunoglobulin G4-related kidney disease.
AB  - Immunoglobulin (Ig) G4-related kidney disease characterizing tubulointerstitial
      nephritis (TIN) is an organ complication recognized in IgG4-related systemic
      diseases that has some unique aspects compared to other types of TIN. TIN lesions
      in the kidney can be tumor-like, focal or diffuse. Abnormal urinalysis is usually
      mild or absent even in the cases with deteriorated renal dysfunction. Some cases
      are accidentally diagnosed from radiological findings without renal dysfunction
      and/or abnormal urinalysis. The typical pathological findings of TIN are unique
      fibrosis and infiltration of massive lymphocytes and IgG4-positive plasma cells.
      Glomerular lesions are rare but the complication of mesangial proliferative
      glomerulonephritis and membranous nephropathy is occasionally reported.
      Pathogenic mechanisms are unclear until now; however, auto-immune and allergic
      mechanisms have been suspected from laboratory data. The initial response to
      steroid agents is generally favorable; however, recurrence is possible after the
      discontinuation of steroid treatment. Long-term follow-up is necessary with
      continuous systemic checks for organ disorders due to IgG4-related systemic
      diseases.

PMID- 21870079
TI  - Antibacterial effect of 317L stainless steel contained copper in prevention of
      implant-related infection in vitro and in vivo.
AB  - Bone and intramedullary bacterial infections are one of the most serious
      complications of the surgical repair of fractures. To reduce the incidence of
      implant-related infections, several biomaterial surface treatments with
      integrated antibiotics, antiseptics, or metal ions have been developed for
      implants. In this study, we evaluated the antibacterial activity and
      biocompatibility of 317L stainless steel containing 4.5% copper alloy (317L-Cu)
      in vitro and in vivo using an animal model. Common pathogens of implant-related
      infections are Staphylococcus aureus and Escherichia coli, which were injected
      into implant materials to study their antimicrobial potential. We compared
      antimicrobial potential of 317L-Cu with 317L stainless steel (317L) and titanium
      (Ti-6Al-4V) alloys as controls. Compared with controls, 317L-Cu materials
      inhibited colonization by both bacteria in vitro and in vivo. Compared with 317L
      and Ti-6Al-4V controls, 317L-Cu showed no significant difference in colony
      formation of osteoblast-like cells on metal surfaces after 72 h of incubation in
      vitro. Metal screws containing these materials were also made for our vivo study
      in a rabbit model. Tissue-implants were analyzed for infection and inflammatory
      changes by hematoxylin-eosin staining of implants in bone. The screw tract
      inflammation and infection of 317L-Cu was minimal, although some inflammatory
      cells gathered at acutely infected sites. In addition, after materials had been
      implanted for 14 days in vivo, the expression of insulin-like growth factor-1
      (IGF-1) in osteoblasts around 317L-Cu screws tracts had increased compared with
      317L and Ti-6Al-4V controls. Overall, 317L-Cu demonstrated strong antimicrobial
      activity and biocompatibility in vitro and in vivo and may be used as a
      biomaterial to reduce implant-related infections.

PMID- 21870080
TI  - Novel hyperbranched polyamidoamine nanoparticles for transfecting skeletal
      myoblasts with vascular endothelial growth factor gene for cardiac repair.
AB  - We investigated the feasibility and efficacy of hyperbranched polyamidoamine
      (hPAMAM) mediated human vascular endothelial growth factor-165 (hVEGF(165)) gene
      transfer into skeletal myoblasts for cardiac repair. The hPAMAM was synthesized
      using a modified one-pot method. Encapsulated DNA was protected by hPAMAM from
      degradation for over 120 min. The transfection efficiency of hPAMAM in myoblasts
      was 82.6 +/- 7.0% with cell viability of 94.6 +/- 1.4% under optimal conditions.
      The hPAMAM showed much higher transfection efficiency (P < 0.05) than
      polyetherimide and Lipofectamine 2000 with low cytotoxicity. The transfected
      skeletal myoblasts gave stable hVEGF(165) expression for 18 days. After
      transplantation of hPAMAM-hVEGF(165) transfected cells, apoptotic myocardial
      cells decreased at day 1 and heart function improved at day 28, with increased
      neovascularization (P < 0.05). These results indicate that hPAMAM-based gene
      delivery into myoblasts is feasible and effective and may serve as a novel and
      promising non-viral DNA vehicle for gene therapy in myocardial infarction.

PMID- 21870081
TI  - Superabsorbent polymer-containing wound dressings have a beneficial effect on
      wound healing by reducing PMN elastase concentration and inhibiting microbial
      growth.
AB  - A comprehensive in vitro approach was used to assess the effects of
      superabsorbent polymer (SAP) containing wound dressings in treatment of non
      healing wounds. A slight negative effect on HaCaT cells was noted in vitro which
      is most likely due to the Ca(2+) deprivation of the medium by binding to the SAP.
      It could be shown that SAP wound dressings are able to bind considerable amounts
      of elastase reducing enzyme activity significantly. Furthermore, SAP's inhibit
      the formation of free radicals. The SAP-containing wound dressings tested also
      exhibited a significant to strong antimicrobial activity effectively impeding the
      growth of gram-negative and gram-positive bacteria as well as yeasts. In
      conclusion, in vitro data confirm the positive effect of SAP wound dressings
      observed in vivo and suggest that they should be specifically useful for wound
      cleansing.

PMID- 21870082
TI  - Influence of some factors affecting antibacterial activity of PVA/Chitosan based
      hydrogels synthesized by gamma irradiation.
AB  - Poly (vinyl alcohol) hydrogels containing different concentrations of chitosan
      with molecular weight of 471 and 101 kDa were crosslinked by gamma irradiation at
      a dose of 25 kGy. The swelling behavior, gel content and morphological structure
      of the blend were investigated. The antibacterial effect, as a function of
      chitosan content and molecular weight in the hydrogel, was investigated against
      Escherichia coli and Bacillus subtilis. With increasing chitosan content the
      equilibrium degree of swelling of the blend increased and the gel fraction
      decreased. Results of antibacterial activity of chitosan revealed that chitosan
      was more effective in inhibiting growth of gram positive bacteria than that of
      gram negative ones. It was observed that, the chitosan content as well as its
      molecular weight has a direct influence on bacteria growth inhibition. The higher
      the chitosan content in the blend and the higher its initial molecular weight,
      the larger was the inhibition zone diameter. The bacteria growth inhibition was
      attributed to the diffusion of entrapped chitosan from the hydrogel blend to the
      culture medium.

PMID- 21870084
TI  - Mg- and Zn-modified calcium phosphates prepared by biomimetic precipitation and
      subsequent treatment at high temperature.
AB  - Powders of magnesium-modified as well as zinc-modified calcium phosphates (Me
      beta-TCP and HA) with a (Ca(2+)+Mg(2+)+Zn(2+)+Na(+)+K(+))/P ratio of 1.3-1.4 and
      various Me(2+)/(Me(2+)+Ca(2+)) ratios (from 0.005 to 0.16) were prepared in
      biomimetic electrolyte systems at pH 8, mother liquid maturation and further
      syntering at 600-1000 degrees C. Some differences in zinc and magnesium
      modifications have been prognosed on the basis of thermodynamic modeling of the
      studied systems and explained by the Mg(2+) and Zn(2+) ion chemical behaviour.
      The temperature as well as the degree of Zn(2+) and Mg(2+) ions substitutions
      were found to stabilize the beta-TCP structure and this effect was more prononced
      for zinc. Thus, zinc-modified beta-TCP powders consisting of idiomorphic crystals
      were obtained through sintering of Zn(2+) ion substituted calcium phosphates
      precursors at 800-1000 degrees C. The Mg(2+) ion substitution leads to obtaining
      magnesium-modified beta-TCP with spherical grains.

PMID- 21870083
TI  - Magnetic bioactive glass ceramic in the system CaO-P2O5-SiO2-MgO-CaF2-MnO2-Fe2O3
      for hyperthermia treatment of bone tumor.
AB  - Magnetic bioactive glass ceramic (MG) in the system CaO-SiO(2)-P(2)O(5)-MgO
      CaF(2)-MnO(2)-Fe(2)O(3) for hyperthermia treatment of bone tumor was synthesized.
      The phase composition was investigated by XRD. The magnetic property was measured
      by VSM. The in vitro bioactivity was investigated by simulated body fluid (SBF)
      soaking experiment. Cell growth on the surface of the material was evaluated by
      co-culturing osteoblast-like ROS17/2.8 cells with materials for 7 days. The
      results showed that MG contained CaSiO(3) and Ca(5)(PO(4))(3)F as the main
      phases, and MnFe(2)O(4) and Fe(3)O(4) as the magnetic phases. Under a magnetic
      field of 10,000 Oe, the saturation magnetization and coercive force of MG were
      6.4 emu/g and 198 Oe, respectively. After soaking in SBF for 14 days,
      hydroxyapatite containing CO(3)(2-) was observed on the surface of MG. The
      experiment of co-culturing cells with material showed that cells could
      successfully attach and well proliferate on MG.

PMID- 21870085
TI  - Diagnostic delay of pediatric brain tumors in Israel: a retrospective risk factor
      analysis.
AB  - PURPOSE: Pediatric brain tumors (PBTs) are the most common solid tumors and the
      leading cause of cancer-related morbidity and mortality in childhood. Previous
      studies have shown a significant delay between the onset of symptoms and the
      diagnosis of these tumors. Delayed diagnosis of PBTs may lead to acute situations
      and irreversible neurological damage. In this study, we looked for the incidence
      of delayed diagnosis of PBTs in Israel. We tried to find the reasons for these
      delays and the associated risk factors in order to provide a feedback to the
      system for improved education and earlier diagnosis. METHODS: We analyzed the
      charts of 330 consecutive children aged 0-18 years diagnosed with brain tumors,
      between the years 1996 and 2004. In the cases where delay in diagnosis was
      suspected, further information was collected from a family interview. RESULTS:
      The average "time to diagnosis" was 7.7 months (SD +/- 16.7). Symptomatic
      deterioration from the first symptom until diagnosis was found in about 50% of
      the cases. Unacceptable delay in diagnosis was found in 27% of the children. The
      major reason for delay was "delay in indicated imaging." Symptoms that were found
      to be associated with delayed diagnosis were torticollis, ataxia, and motor
      dysfunction. Interestingly, the examination by specialists such as
      ophthalmologists or neurologists was also associated with delayed diagnosis.
      CONCLUSIONS: There is an unacceptable rate of delay in the diagnostic process of
      PBTs in Israel. Greater awareness and familiarity with signs and symptoms
      associated with these tumors and lowering imaging threshold might minimize this
      phenomenon.

PMID- 21870086
TI  - Detection of visual field progression in glaucoma with standard achromatic
      perimetry: a review and practical implications.
AB  - Detection of visual field progression remains a challenging task despite the
      recent advances for better handling of longitudinal visual field data, some of
      which are incorporated in currently available perimeters. Standard achromatic
      perimetry remains the gold standard for detection of visual field progression.
      The authors present a practical and clinically relevant review of the main issues
      involved in detection of early glaucoma as well as detection of visual field
      progression in eyes with pre-existing glaucomatous damage. After discussing some
      basic concepts in perimetry, the authors present evidence-based recommendations
      for criteria to detect earliest evidence of glaucomatous damage with perimetry.
      The authors will review different event- and trend-based criteria and present
      data with regard to comparative performance of such criteria. Relevance of using
      absolute versus corrected threshold data with regard to different criteria is
      also addressed. At the end, the authors provide practical guidelines for
      detection of visual field progression in a clinical setting and review issues
      related to clinical trials.

PMID- 21870087
TI  - The effect of subretinal viscoelastics on the porcine retinal function.
AB  - The functional consequence of long-term retinal detachment in the porcine model
      is examined by multifocal electroretinography (mfERG). Retinal detachment (RD) in
      humans leaves permanent visual impairment, despite anatomical successful
      reattachment surgery. To improve treatment, adjuvant pharmaceutical therapy is
      needed, and can only be tested in a suitable animal model. The porcine model is
      promising and the mfERG is well validated in this model. RD was induced in 18
      pigs by vitrectomy and healon injection of various concentrations. Preoperatively
      and 6 weeks postoperatively eight animals were examined by mfERG. The major
      component P1 was analyzed statistically. Indirect ophthalmoscopy and bilateral
      color fundus photography (FP) were performed. Selected animals underwent high
      resolution optical coherence tomography (OCT). Examination by ophthalmoscopy and
      FP showed that the RDs remained detached for the 6 weeks of follow-up. The P1
      amplitude of the mfERG did not differ significantly between the detached areas,
      the surrounding attached areas, and the healthy eye (p = 0.25). Similarly, P1
      implicit time did not differ between the areas (p = 0.85). The lack of functional
      consequences of long-term RD makes the porcine model unsuitable for examining
      adjuvant pharmaceutical RD treatment. Future studies should focus on foveated
      primates.

PMID- 21870089
TI  - Quality of life in children on dialysis.
AB  - INTRODUCTION: In recent years, the survival of patients with end stage renal
      disease (ESRD) has increased but few studies have assessed the quality of life in
      children on dialysis. The aim of the present cross-sectional study was to analyze
      the quality of life in this pediatric population and compare it with healthy
      controls using the Autoquestionnaire Qualite de Vie Enfant Image. SUBJECTS:
      Thirty-three children on dialysis paired for gender, age, and social level with
      33 healthy children. RESULTS: A significant difference was observed between the
      groups regarding the question on the practicing of sports. For this question,
      29/33 healthy children reported to be very satisfied, while only 17/33 out of the
      ESRD group stated likewise. When asked about satisfaction of the children at the
      table with the family, 23/33 of the controls and 16/33 of the ESRD group reported
      to be very satisfied, showing a trend toward a significant difference (P =
      0.059). No differences were observed for the remaining questions. We conclude
      that ESRD was linked to lower perception of quality of life in leisure aspects
      (sports) and a trend regarding functional issues (meal at the table).

PMID- 21870088
TI  - Effect of nutritional vitamin D preparations on parathyroid hormone in patients
      with chronic kidney disease.

PMID- 21870090
TI  - Bladder carcinoma in a 31-year-old female spina bifida patient with an auto
      augmented bladder.
AB  - We present the case of a 31-year-old spina bifida patient presenting with a
      poorly differentiated T3N1M0 bladder carcinoma with sarcomatoid differentiation
      in an auto-augmented bladder. She underwent a radical cystectomy and a bilateral
      lymph node dissection. However, only 10 months after the onset of her symptoms,
      she died after major lymphatic metastases had developed in the small pelvis. This
      case report is the first on an adult spina bifida patient developing bladder
      carcinoma after detrusorectomy. It shows that bladder cancer also occurs in
      patients who underwent detrusorectomy, despite the fact that the risk is
      supposedly lower than in patients who underwent enterocystoplasty. Moreover,
      tumour spread to adjacent organs could occur more rapidly in auto-augmented
      bladders because of the lack of muscle tissue. The latter could have serious
      implications on the prognosis of these patients.

PMID- 21870093
TI  - Unilateral mydriasis due to scopolamine patch.
AB  - CASE: We report the case of a patient who presented with unilateral mydriasis
      after a scopolamine patch application. The specific clinical context (cancer)
      reported here may have led to the misinterpretation of the etiology of mydriasis.
      CONCLUSION: Our case description warns against diagnostic mistakes related to
      this side effect and highlights the advantages of pilocarpine test in the
      differential diagnosis of unilateral mydriasis.

PMID- 21870095
TI  - Anatomy of subaxial cervical foramens: the safety zone for lateral mass screwing.
AB  - INTRODUCTION: The purpose of this study was to measure the structures of the
      ventral of lateral masses using cadaver specimens and to quantitatively compare
      the safety zone for the two major techniques used on each vertebral level from C3
      to C6. METHODS: This study is based on 52 cervical vertebrae of 13 cadavers. The
      anatomical measurements focused on the anterior surface of the lateral mass. We
      investigated the safety width, heights, and the height of nerve roots. RESULTS:
      The mean values of the safety width of the Magerl technique from C3 to C6 were
      6.1, 7.3, 6.4 and 4.3 mm, respectively. The mean values of the safety width of
      the Roy-Camille technique were 6.7, 6.6, 5.8 and 5.4 mm, respectively. The mean
      values of the safety height of the Magerl technique were 5.0, 5.4, 5.8 and 5.2
      mm, respectively. The mean values of the safety height of the Roy-Camille
      technique were 4.9, 4.0, 1.0 and -1.2 mm, respectively. The mean values of the
      nerve root height were 3.9, 4.9, 5.9 and 6.9 mm, respectively. CONCLUSION: The
      safety width of the Magerl technique was shorter at C6 because the vertebral
      artery runs more laterally at C6. The height for the Magerl technique was not
      significantly different from C3 to C6, however, the safety height for the Roy
      Camille technique was significantly shorter at C5 and C6. Our findings suggest
      that it is important to ensure that the screw(s) penetrate through the cranial
      side of the ventral aspect of a lateral mass when performing the Magerl technique
      at all vertebral levels, and to carefully select the screw length when using the
      Roy-Camille technique, especially at C5 and C6, in order to avoid nerve root
      injury.

PMID- 21870094
TI  - The liver prometastatic reaction of cancer patients: implications for
      microenvironment-dependent colon cancer gene regulation.
AB  - Colon cancer frequently metastasizes to the liver but the genetic and phenotypic
      properties of specific cancer cells able to implant and grow in this organ have
      not yet been established. The contribution of the patient's genetic, physiologic
      and pathologic backgrounds to the incidence and development of hepatic colon
      cancer metastases is also presently misunderstood. At a transcriptional level,
      hepatic metastasis development is in part associated with marked changes in gene
      expression of colon cancer cells that may originate in the primary tumor. Other
      changes occur in the liver and are regulated by hepatic cells, which represent
      the new microenvironment for metastatic colon cancer cells. However, hepatic
      parenchymal and non-parenchymal cell functions are also affected by both tumor
      derived factors and systemic host factors, which suggests that the hepatic
      metastasis microenvironment is a functional linkage between the hepatic
      pathophysiology of the colon cancer patient and the biology of its cancer cells.
      Therefore, together with metastasis-related gene profiles suggesting the
      existence of liver metastasis potential in primary tumors, new biomarkers of the
      prometastatic microenvironment supported by the liver reaction to colon cancer
      factors may be helpful for the individual assessment of hepatic metastasis risk
      in colon cancer patients. In addition, knowledge on hepatic metastasis gene
      regulation by the hepatic microenvironment may open multiple opportunities for
      therapeutic intervention during colon cancer metastasis at both subclinical and
      advanced stages.

PMID- 21870096
TI  - Global analysis of sagittal spinal alignment in major deformities: correlation
      between lack of lumbar lordosis and flexion of the knee.
AB  - INTRODUCTION: It has become well recognised that sagittal balance of the spine is
      the result of an interaction between the spine and the pelvis. Knee flexion is
      considered to be the last compensatory mechanism in case of sagittal imbalance,
      but only few studies have insisted on the relationship between spino-pelvic
      parameters and lower extremity parameters. Correlation between the lack of lumbar
      lordosis and knee flexion has not yet been established. MATERIALS AND METHODS: A
      retrospective study was carried out on 28 patients with major spinal deformities.
      The EOS system was used to measure spinal and pelvic parameters and the knee
      flexion angle; the lack of lumbar lordosis was calculated after prediction of
      lumbar lordosis with two different formulas. Correlation analysis between the
      different measured parameters was performed. RESULTS: Lumbar lordosis correlated
      with sacral slope (r = -0.71) and moderately with knee flexion angle (r = 0.42).
      Pelvic tilt correlated moderately with knee flexion angle (r = 0.55). Lack of
      lumbar lordosis correlated best with knee flexion angle (r = 0.72 and r = 0.63
      using the two formulas, respectively). CONCLUSION: Knee flexion as a compensatory
      mechanism to sagittal imbalance was well correlated to the lack of lordosis and,
      depending on the importance of the former parameter, the best procedure to
      correct sagittal imbalance could be chosen.

PMID- 21870097
TI  - Sagittal spino-pelvic alignment in chronic low back pain.
AB  - INTRODUCTION: The differences in sagittal spino-pelvic alignment between adults
      with chronic low back pain (LBP) and the normal population are still poorly
      understood. In particular, it is still unknown if particular patterns of sagittal
      spino-pelvic alignment are more prevalent in chronic LBP. The current study helps
      to better understand the relationship between sagittal alignment and low back
      pain. MATERIALS AND METHODS: To compare the sagittal spino-pelvic alignment of
      patients with chronic LBP with a cohort of asymptomatic adults. Sagittal spino
      pelvic alignment was evaluated in prospective cohorts of 198 patients with
      chronic LBP and 709 normal subjects. The two cohorts were compared with respect
      to the sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar
      lordosis (LL), lumbar tilt (LT), lordotic levels, thoracic kyphosis (TK),
      thoracic tilt (TT), kyphotic levels, and lumbosacral joint angle (LSA).
      Correlations between parameters were also assessed. RESULTS: Sagittal spino
      pelvic alignment is significantly different in chronic LBP with respect to SS,
      PI, LT, lordotic levels, TK, TT and LSA, but not PT, LL, and kyphotic levels.
      Correlations between parameters were similar for the two cohorts. As compared to
      normal adults, a greater proportion of patients with LBP presented low SS and LL
      associated with a small PI, while a greater proportion of normal subjects
      presented normal or high SS associated with normal or high PI. CONCLUSION:
      Sagittal spino-pelvic alignment was different between patients with chronic LBP
      and controls. In particular, there was a greater proportion of chronic LBP
      patients with low SS, low LL and small PI, suggesting the relationship between
      this specific pattern and the presence of chronic LBP.

PMID- 21870098
TI  - Kernel lysine content does not increase in some maize opaque2 mutants.
AB  - The recessive mutant allele of the opaque2 gene (o2) alters the endosperm protein
      pattern and increases the kernel lysine content of maize (Zea mays L.). In this
      study, sequencing results showed that the o2 mutant was successfully introgressed
      into 12 elite normal maize inbred lines by marker assisted selection (MAS). The
      average genetic similarity between these normal inbred lines and their o2 near
      isogenic lines (NILs) was more than 95%. Kernel lysine content increased
      significantly in most of o2 NILs lines relative to normal elite inbreds, but
      remained unchanged in the genetic backgrounds Dan598o2 and Liao2345o2. Moreover,
      the kernel characteristics of these two o2 NILs did not differ from the other
      inbred lines. The results of lysine content analysis in the F1 hybrids between
      Liao2345o2 and Dan598o2 and other o2 NILs demonstrated that gene(s) other than
      opaque2 may control kernel lysine content in these two o2 NILs. The results of
      zein analysis showed that 22-kD alpha-zein synthesis was reduced or absent, and
      the 19-kD alpha-zein synthesis was greatly reduced compared with the recurrent
      parents in most o2 NILs except for Dan598o2 and Liao2345o2. Our results indicate
      that gene(s) other than opaque2 may play more important roles in zein synthesis
      and kernel lysine content in some maize genetic backgrounds.

PMID- 21870100
TI  - Immobilization of Candida rugosa lipase on poly(3-hydroxybutyrate-co
      hydroxyvalerate): a new eco-friendly support.
AB  - The overall objective of this study is to evaluate the morphological [scanning
      electron microscopy (SEM)], physicochemical [differential scanning calorimetry
      (DSC), thermogravimetric analysis (TGA), chemical composition analysis, Fourier
      transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR)], and
      biochemical properties of Candida rugosa lipase (CRL) immobilized on a natural
      biopolymer poly(3-hydroxybutyrate-co-hydroxyvalerate) (PHBV) in aqueous solution.
      CRL was immobilized by physical adsorption with efficiency of 30%. Compared with
      free CRL enzyme, there were slight changes in immobilized CRL activity as a
      function of temperature (from 37 degrees C to 45 degrees C), but a similar
      optimal pH value of 7.0. Inactivation rate constants for immobilized CRL enzyme
      were 0.009 and 0.334 h-1, and half-lives were 77 and 2 h at 40 degrees C and 60
      degrees C, respectively. Kinetic parameters obtained for immobilized CRL include
      the Michaelis-Menten constant of K(m) = 213.18 mM and maximum reaction velocity
      of V(max) = 318.62 U/g. The operational stability of immobilized CRL was tested
      repeatedly, and after 12 cycles of reuse, the enzyme retained 50% activity. Based
      on our results, we propose that PHBV-immobilized CRL could serve as a promising
      biocatalyst in several industrial applications.

PMID- 21870101
TI  - Less wear with aluminium-oxide heads than cobalt-chrome heads with ultra high
      molecular weight cemented polyethylene cups: a ten-year follow-up with
      radiostereometry.
AB  - PURPOSE: Wear is a major contributor to osteolysis and aseptic loosening of total
      hip replacements (THR). Both alumina (Al(2)O(3)) and cobalt-chrome (CoCr) femoral
      heads are commonly used. We investigated wear comparing alumina heads to cobalt
      chrome heads against conventional cemented polyethylene (PE) cups for up to ten
      years. METHODS: Linear wear was measured with radiostereometry (RSA). Our
      material was derived from two prospective randomised trials that investigated
      fixation of femoral stems, not wear, and was evaluated retrospectively (Level
      III). RESULTS: The mean (95% CI) proximal head penetration was 0.96 mm (0.68
      1.23) in the cobalt-chrome group and 0.42 mm (0.30-0.53) in the alumina group at
      ten years (P = 0.001). The mean (95% CI) 3D penetration was 1.07 mm (0.79-1.35)
      and 0.53 mm (0.38-0.63), respectively, at ten years (P = 0.001). CONCLUSION:
      Alumina heads performed better than cobalt-chrome heads in this study after ten
      year follow-up.

PMID- 21870102
TI  - Transcript signature predicts tissue NK cell content and defines renal cell
      carcinoma subgroups independent of TNM staging.
AB  - Clear cell renal cell carcinoma (ccRCC) is an aggressive and difficult to manage
      cancer. Immunotherapy has the potential to induce long-lasting regression in a
      small group of patients. However, severe side effects limit broad application
      which highlights the need for a marker to distinguish responder from
      nonresponder. TNMG staging, referring to tumor size, lymph node involvement,
      presence of metastasis, and grade of tumor differentiation, represents an
      important prognostic system but is not useful for predicting responders to
      immunotherapy. NK cells are potent antitumor effector cells, and a role as
      prognostic marker in some solid tumors has been suggested. As NK cells are
      responsive to various immune modifiers, they may be important mediators of
      patient response to immunotherapies, in particular those including IL-2. We
      report that the NK cell percentage within RCC-infiltrating lymphocytes, as
      determined by flow cytometry, allows ccRCC subgrouping in NK(high)/NK(low)
      tissues independent of TNMG classification. Quantitative reverse transcriptase
      polymerase chain reaction using whole-tissue RNA identified four markers (NKp46,
      perforin, CX(3)CL1, and CX(3)CR1) whose transcript levels reproduced the
      NK(high)/NK(low) tissue distinction identified by flow cytometry with high
      selectivity and specificity. Combined in a multiplex profile and analyzed using
      neural network, the accuracy of predicting the NK(high)/NK(low) groups was 87.8%,
      surpassing that of each single marker. The tissue transcript signature, based on
      a robust high-throughput methodology, is easily amenable to archive material and
      clinical translation. This now allows the analysis of large patient cohorts to
      substantiate a role of NK cells in cancer progression or response to
      immunotherapy.

PMID- 21870103
TI  - Anxiety and depression, chronic physical conditions, and quality of life in an
      urban population sample study.
AB  - OBJECTIVE: No previous studies have empirically demonstrated a multiplicative
      interactive effect of anxiety disorders and/or depression (ADD) and chronic
      medical conditions on quality of life (QOL). We hypothesized that QOL impairment
      was worsened by the presence of ADD and medical co-morbidity, more than when it
      was with either medical co-morbidity alone or ADD alone. METHODS: Complete data
      of 2,801 participants from the National Mental Health Survey of Adults in
      Singapore were analyzed, using SCAN diagnoses of anxiety disorders and
      depression, self-reports of chronic medical conditions, and SF-12 measures of QOL
      (Mental Component Summary, MCS, and Physical Component Summary, PCS). RESULTS:
      Persons diagnosed with ADD (compared to those without) had considerably more
      medical co-morbidities (59 vs. 33%, p < 0.001). In multiple regression analyses,
      ADD (vs. no ADD) was associated with lower PCS (b = -1.013, p = 0.045) and MCS
      scores (b = -9.912, p < 0.001), as was number of medical co-morbidities (0, 1-2,
      3 +), PCS scores (b = -2.058, p < 0.001) and MCS scores (b = -1.138, p < 0.001).
      There were significant interactive effects of medical co-morbidities and ADD on
      PCS (p < 0.001), and MCS (p = 0.086), suggesting that the negative effects of
      medical conditions on quality of life was aggravated non-additively by the co
      morbid presence of ADD, and vice versa. CONCLUSION: The individual effects of
      medical and psychiatric morbidity on functional status and quality of life were
      considerably worse when both were present in the same individual. Future studies
      should examine the impact of identifying and treating anxiety and depressive
      disorders in patients with medical problems for better outcomes.

PMID- 21870104
TI  - Vasculitis in Sjogren's Syndrome.
AB  - Sjogren's syndrome is a chronic autoimmune disease that is commonly manifested by
      immune attack on the exocrine glands with resultant dry eyes and dry mouth.
      Sjogren's syndrome patients also have disease in other organs. One of the most
      common extraglandular manifestations is vasculitis. Skin vasculitis, with
      palpable purpura clinically and leukocytoclastic vasculitis on pathological
      examination, is common. Although half of those individuals with subcutaneous
      vasculitis have only a single episode, skin vasculitic involvement is associated
      with more severe disease. Necrotizing vasculitis of medium-sized vessels
      resembling polyarteritis nodosa can occur in Sjogren's syndrome patients.
      Experience in therapy for vasculitis is limited, but intravenous IgG may be
      effective. Recent data support a relationship between neuromyelitis optica (Devic
      disease) and Sjogren's syndrome. Sjogren's syndrome patients with optic neuritis
      or transverse myelitis have anti-aquaporin-4, which are characteristic of Devic
      disease. Devic disease patients have salivary lymphocytic infiltration similar to
      that found among Sjogren's syndrome patients.

PMID- 21870105
TI  - A contact anti-aphrodisiac pheromone supplied by the spermatophore in the rove
      beetle Aleochara curtula: mode of transfer and evolutionary significance.
AB  - By reducing the attractiveness of their mating partner via an anti-aphrodisiac
      pheromone, males can prevent a remating of the female and thus reduce the risk of
      sperm competition. For females, the main benefit from allowing the chemical
      manipulation of their attractiveness is probably the avoidance of sexual
      harassments from rival males. While mating plugs generally constitute a physical
      barrier which hinders male mating attempts, chemical manipulations must
      trustfully inform the responding male of the female's reluctance to mate;
      otherwise, it would be beneficial to ignore the repellent information. In our
      experiments, males of the polyandrous rove beetle Aleochara curtula chemically
      manipulated the attractiveness of their mating partner. Coincident with the
      deposition of a spermatophore into the female genital chamber, an anti
      aphrodisiac pheromone was transferred and readily spread onto the female surface,
      where it was subsequently perceived by rival males via parameres, the claspers of
      the male genitalia. Males aborted contact with the mated female to avoid further
      time- and energy-consuming elements of the mating sequence. The chemical mode of
      action was demonstrated inter alia by spicing virgin females with spermatophore
      extracts. The action of the anti-aphrodisiac correlated with the persistence of
      the spermatophore in the female genital chamber and corresponded to the length of
      stay of the mated female at a carcass, where the density of rival males is
      highest. The ensuing benefits for all three parties involved in this
      communication system, which render this post-copulatory mate guarding strategy
      evolutionary stable, are discussed.

PMID- 21870107
TI  - Gastrointestinal tract specific gene GDDR inhibits the progression of gastric
      cancer in a TFF1 dependent manner.
AB  - The novel gene GDDR, also named trefoil factor interactions 1, is abundantly
      expressed in human gastric epithelial cells but significantly down-regulated in
      gastric cancer. In this study, we first demonstrated that GDDR was specifically
      expressed in the gastrointestinal tract epithelium, while suppressed in gastric
      cancer cells. Forced expression of GDDR suppressed the tumor growth as shown by
      MTT and xenograft assay. siRNA mediated TFF1 inhibition nearly blocked the growth
      inhibitory role of GDDR. In summary, our study suggested that gastrointestinal
      tract specific gene GDDR might inhibit gastric cancer growth in a TFF1 dependent
      manner.

PMID- 21870106
TI  - Repeated administration of berberine inhibits cytochromes P450 in humans.
AB  - PURPOSE: Berberine is a plant alkaloid that is widely used to treat
      gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia.
      Many studies have reported interactions between berberine-containing products and
      cytochromes P450 (CYPs), but little is known about whether berberine alters CYP
      activities in humans, especially after repeated doses. METHODS: A two-phase
      randomized-crossover clinical study in healthy male subjects was performed. After
      2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam,
      omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme
      activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively. RESULTS: A
      decrease in CYP2D6 activity was observed as the 0-8 h urinary
      dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition,
      losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a
      decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the C(max),
      AUC(0-infinity), and AUC(0-12) of midazolam were increased 38% (P < 0.05), 40% (P
      < 0.01), and 37% (P < 0.05) after BBR treatment, respectively. Compared with the
      placebo period, the T(max) and T(1/2) of midazolam during BBR administration were
      prolonged from 3.03 +/- 0.27 to 3.66 +/- 0.37 h and 0.66 +/- 0.08 to 0.99 +/-
      0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P <
      0.05); and the phenotypic indices of 1 h midazolam/1'-hydroxymidazolam increased
      59% (P < 0.01). There were no statistically significant differences in the
      pharmacokinetic parameters of the other probe drugs between placebo and the BBR
      treated group. CONCLUSIONS: Repeated administration of berberine (300 mg, t.i.d.,
      p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should
      be considered when berberine is administered.

PMID- 21870108
TI  - Evaluation of an on-site pilot static granular bed reactor (SGBR) for the
      treatment of slaughterhouse wastewater.
AB  - An on-site pilot-scale static granular bed reactor (SGBR) system was evaluated
      for treating wastewater from a slaughterhouse in Iowa. The study evaluated SGBR
      reactor suitability for slaughterhose wastewater having high particulate COD
      concentration (7.9 +/- 4.3 g COD/L) at 0.3-1.4 m(3)/m(2)/day of the surface
      loading rates. High organic removal efficiency (over 95% of TSS and VSS removal)
      was obtained due to the consistent treatability of SGBR system during operation
      at HRTs of 48, 36, 30, 24, and 20 h. The average effluent TSS, VSS, COD, soluble
      COD, and BOD(5) concentrations were 84, 71, 301,197, and 87 mg/L, respectively.
      An effective backwash procedure was performed once every 7-14 days to waste a
      portion of the accumulated solids in the system. This procedure limited the
      increase in hydraulic head loss and maintained the system stability. COD removal
      efficiencies greater than 95% were achieved at organic loading rates ranging from
      0.77 to 12.76 kg/m(3)/day.

PMID- 21870110
TI  - Wnt5a potentiates U46619-induced platelet aggregation via the PI3K/Akt pathway.
AB  - Platelet aggregation plays crucial roles in the formation of hemostatic plugs and
      thrombosis. Although it was recently shown that canonical Wnt signaling
      negatively regulates platelet aggregation, the role of non-canonical Wnt
      signaling remains unknown. Here, we observed that Wnt5a, one of the non-canonical
      Wnts, positively regulated platelet aggregation. Platelet aggregation was
      potentiated by the addition of Wnt5a to collagen-or U46619-induced rat platelet
      rich plasma (PRP). Treatment with Wnt5a to U46619-stimulated PRP resulted in an
      increase in the level of phosphorylated Akt, whereas phosphorylation of PKCdelta
      and JNK1 was unaffected. In addition, inhibition of PI3K blocked the potentiating
      effect of Wnt5a. Taken together, these results suggest that Wnt5a potentiates
      U46619-induced platelet aggregation via the PI3K/Akt pathway.

PMID- 21870109
TI  - Roles of mitogen-activated protein kinase cascades in ABA signaling.
AB  - Abscisic acid (ABA) is a universal hormone in higher plants and plays a major
      role in various aspects of plant stress, growth, and development. Mitogen
      activated protein kinase (MAPK) cascades are key signaling modules for responding
      to various extracellular stimuli in plants. The available data suggest that MAPK
      cascades are involved in some ABA responses, including antioxidant defense, guard
      cell signaling, and seed germination. Some MAPK phosphatases have also been
      demonstrated to be implicated in ABA responses. The goal of this review is to
      piece together the findings concerning MAPK cascades in ABA signaling. Questions
      and further perspectives of the roles played by MAPK cascades in ABA signaling
      are also furnished.

PMID- 21870111
TI  - A systematic analysis of Drosophila gustatory receptor gene expression in
      abdominal neurons which project to the central nervous system.
AB  - In Drosophila, the gustatory receptor (Gr) gene family contains 60 family members
      that encode 68 proteins through alternative splicing. Some gustatory receptors
      (Grs) are involved in the sensing of sugars, bitter substrates, CO(2),
      pheromones, and light. Here, we systematically examined the expression of all 68
      Grs in abdominal neurons which project to the abdominal ganglion of the central
      nervous system using the GAL4/UAS system. Gr gene expression patterns have been
      successfully analyzed in previous studies by using the GAL4/UAS system to drive
      reporter gene expression. Interestingly, 21 Gr-GAL4 drivers showed abdominal
      ganglion projection, and 18 of these 21 Gr-GAL4 drivers labeled multidendritic
      neurons of the abdominal wall. 4 drivers also labeled neuronal processes
      innervating the reproductive organs. The peripheral expression of Gr-GAL4 drivers
      in abdominal multidendritic neurons or neurons innervating the reproductive
      organs suggests that these Grs have atypical sensory functions in these organs
      not limited to conventional taste sensing.

PMID- 21870112
TI  - Dramatic increase in the signal and sensitivity of detection via self-assembly of
      branched DNA.
AB  - In molecular testing using PCR, the target DNA is amplified via PCR and the
      sequence of interest is investigated via hybridization with short oligonucleotide
      capture probes that are either in a solution or immobilized on solid supports
      such as beads or glass slides. In this report, we report the discovery of
      assembly of DNA complex(es) between a capture probe and multiple strands of the
      PCR product. The DNA complex most likely has branched structure. The assembly of
      branched DNA was facilitated by the product of asymmetric PCR. The amount of
      branched DNA assembled was increased five fold when the asymmetric PCR product
      was denatured and hybridized with a capture probe all in the same PCR reaction
      mixture. The major branched DNA species appeared to contain three reverse strands
      (the strand complementary to the capture probe) and two forward strands. The DNA
      was sensitive to S1 nuclease suggesting that it had single-stranded gaps.
      Branched DNA also appeared to be assembled with the capture probes immobilized on
      the surface of solid support when the product of asymmetric PCR was hybridized.
      Assembly of the branched DNA was also increased when hybridization was performed
      in complete PCR reaction mixture suggesting the requirement of DNA synthesis.
      Integration of asymmetric PCR, heat denaturation and hybridization in the same
      PCR reaction mixture with the capture probes immobilized on the surface of solid
      support achieved dramatic increase in the signal and sensitivity of detection of
      DNA. Such a system should be advantageously applied for development of automated
      process for detection of DNA.

PMID- 21870114
TI  - The reputation of psychiatry in the first half of the twentieth century.
AB  - The article evaluates the arguments used by German psychiatrists in the first
      half of the twentieth century to raise their professional reputation. The
      arguments, which were used in Wilhelmine Germany and in the 1920s, changed with
      the establishment of the NS-regime. While psychiatrists claimed for open care
      systems and for more transparency of psychiatric practice to the public in the
      first decades of the twentieth century, psychiatry became a crucial part of NS
      health policies after 1933. The psychiatrist's participation in the largest
      systematic action to kill mentally ill patients known in history forced them to
      search for ways to legitimatize the murder program and to integrate it into a
      therapeutical view of future psychiatry by trying to avoid arbitrariness and
      assigning research a central importance.

PMID- 21870113
TI  - Pim protein kinase-3 is regulated by TNF-alpha and promotes endothelial cell
      sprouting.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in pathological
      angiogenesis associated with inflammatory response. Pim-3 kinase belonging to
      serine/threonine protein kinases is a potent suppressor of myc-induced apoptosis.
      We have recently demonstrated that Pim-3 plays an essential role in endothelial
      cell (EC) spreading and migration. In this study, we showed that TNF-alpha
      transiently increased Pim-3 mRNA expression, and this was mediated through Tumor
      necrosis factor-alpha receptor-1 (TNFR1) pathway in ECs. TNF-alpha could promote
      stabilization of Pim- 3 mRNA in ECs. Small-interfering RNA (siRNA)-mediated gene
      knockdown of Pim-3 significantly impaired TNF-alpha-induced formation of EC
      membrane protrusions in vitro. Furthermore, Pim-3 silencing inhibited EC
      sprouting in subcutaneous Matrigel in vivo. eNOS mRNA abundance was lower in Pim
      3 siRNA transfected ECs compared with the control ECs. These observations suggest
      that Pim-3 plays a role in TNF-alpha-induced angiogenesis.

PMID- 21870115
TI  - Apology, responsibility, memory. Coming to terms with Nazi medical crimes: the
      example of the Max Planck Society.
AB  - In June 2001, the then president of the Max Planck Society addressed a formal
      apology to survivors of Nazi medical crimes. Starting from this ritual of
      repentance, the paper examines the participants' diverse views of how to deal
      with the medical crimes of National Socialism. In comparison with the DGPPN, it
      asks about possibilities of going beyond historical retrospection to fulfil the
      imperative of remembrance.

PMID- 21870116
TI  - Functional evaluation of cystic duct patency with Gd-EOB-DTPA MR imaging: an
      alternative to hepatobiliary scintigraphy for diagnosis of acute cholecystitis?
AB  - PURPOSE: To determine if MR cholangiography with Gd-EOB-DTPA can be used to
      assess cystic duct patency and to establish normal time range for reflux of
      contrast material into the cystic duct/gallbladder. MATERIALS AND METHODS: This
      retrospective study is HIPAA-compliant and IRB-approved with waiver for informed
      consent granted. From September 2008 to June 2009, 300 patients who underwent Gd
      EOB-DTPA-enhanced MR imaging for various clinical indications, not specifically
      limited to evaluation for acute cholecystitis, were identified. 112 patients were
      excluded: prior cholecystectomy (n = 93), severe technical limitations (n = 9),
      or absence of appropriate clinical follow-up (n = 10). 188 total patients (82
      male, 106 female, mean age 51.0 years) were included in the final dataset. Time
      between contrast administration and contrast reflux into the cystic
      duct/gallbladder on delayed phase imaging was measured. RESULTS: Reflux of
      contrast into the gallbladder was identified in 130/188 patients (69.1%) on
      delayed phase imaging. Average time to gallbladder reflux was 15:24 +/- 5:51
      minutes (range: 6:01-41:05 min). 58/188 patients (30.9%) demonstrated no reflux
      of contrast into the gallbladder at time of final delayed phase images. Of 58
      patients who demonstrated no reflux into cystic duct/gallbladder, 15 patients
      demonstrated no extrahepatic biliary excretion, limiting evaluation of cystic
      duct patency. A total of 173 patients demonstrated biliary excretion of contrast
      with 76% overall sensitivity of detection of cystic duct patency. CONCLUSION: MR
      cholangiography with hepatobiliary MR contrast agents such as Gd-EOB-DTPA can
      demonstrate cystic duct patency with high sensitivity. MR protocols can be
      designed within a clinically feasible timeframe to optimize diagnosis of acute
      cholecystitis.

PMID- 21870117
TI  - Conditional Allele Mouse Planner (CAMP): software to facilitate the planning and
      design of breeding strategies involving mice with conditional alleles.
AB  - Transgenic and conditional knockout mouse models play an important role in
      biomedical research and their use has grown exponentially in the last 5-10 years.
      Generating conditional knockouts often requires breeding multiple alleles onto
      the background of a single mouse or group of mice. Breeding these mice depends on
      parental genotype, litter size, transmission frequency, and the number of
      breeding rounds. Therefore, a well planned breeding strategy is critical for
      keeping costs to a minimum. However, designing a viable breeding strategy can be
      challenging. With so many different variables this would be an ideal task for a
      computer program. To facilitate this process, we created a Java-based program
      called Conditional Allele Mouse Planner (CAMP). CAMP is designed to provide an
      estimate of the number of breeders, amount of time, and costs associated with
      generating mice of a particular genotype. We provide a description of CAMP, how
      to use it, and offer it freely as an application.

PMID- 21870118
TI  - A phase II trial of thalidomide and procarbazine in adult patients with recurrent
      or progressive malignant gliomas.
AB  - Thalidomide and procarbazine have demonstrated single agent activity against
      malignant gliomas (MG). We evaluated the combination of thalidomide and
      procarbazine with a single arm phase II trial in adults with recurrent or
      progressive MG. Procarbazine was given at a dose of 250 mg/m(2)/d * 5day q 28
      days. Thalidomide was administered at a dose of 200 mg/day continuously.
      Intrapatient dose escalation of thalidomide was attempted (increase by 100 mg/day
      weekly as tolerated) to a maximum of 800 mg/day. The primary outcome was tumor
      response, assessed by MRI and CT. Secondary outcomes were progression free
      survival (PFS), overall survival (OS) and toxicity. In addition, quality of life
      questionnaires were performed at baseline and prior to each odd cycle in all
      treated patients. Eighteen patients (median age of 50) were accrued and received
      a total of 36 cycles (median 2) of therapy. The median maximum thalidomide dose
      achieved was 400 mg (range 0-800). No complete or partial responses were seen.
      One patient (6%) experienced stable disease, fourteen (78%) progressed as best
      response and three (17%) were not evaluable for response. Median time to
      progression was 2.1 months (95% CI, 1.5-2.5). Seventeen patients have died (one
      patient lost to follow-up after progression); median survival from enrollment was
      7.6 months (95% CI, 3.5-9.4). Grade 3/4 drug related toxicity was minimal.
      Quality of life diminished over time. The combination of thalidomide and
      procarbazine demonstrated no efficacy in this trial.

PMID- 21870119
TI  - Motor unit recruitment during neuromuscular electrical stimulation: a critical
      appraisal.
AB  - Neuromuscular electrical stimulation (NMES) is commonly used in clinical settings
      to activate skeletal muscle in an effort to mimic voluntary contractions and
      enhance the rehabilitation of human skeletal muscles. It is also used as a tool
      in research to assess muscle performance and/or neuromuscular activation levels.
      However, there are fundamental differences between voluntary- and artificial
      activation of motor units that need to be appreciated before NMES protocol design
      can be most effective. The unique effects of NMES have been attributed to several
      mechanisms, most notably, a reversal of the voluntary recruitment pattern that is
      known to occur during voluntary muscle contractions. This review outlines the
      assertion that electrical stimulation recruits motor units in a nonselective,
      spatially fixed, and temporally synchronous pattern. Additionally, it synthesizes
      the evidence that supports the contention that this recruitment pattern
      contributes to increased muscle fatigue when compared with voluntary actions and
      provides some commentary on the parameters of electrical stimulation as well as
      emerging technologies being developed to facilitate NMES implementation. A
      greater understanding of how electrical stimulation recruits motor units, as well
      as the benefits and limitations of its use, is highly relevant when using this
      tool for testing and training in rehabilitation, exercise, and/or research.

PMID- 21870121
TI  - Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy:
      a randomized and controlled clinical trial.
AB  - The aim of this study was to investigate the effects of ALC treatment on
      cognitive functions in patients with severe hepatic encephalopathy. This was a
      randomized, double-blind, placebo-controlled study. 61 patients with severe
      hepatic encephalopathy were recruited to the study. The 2 groups received either
      2 g ALC twice a day (n = 30) or placebo (n = 30) for 90 days. Clinical and
      laboratory assessment, psychometric tests and automated electroencephalogram
      (EEG) analysis were performed for all patients. At the end of the study period,
      between the 2 groups we observed a significant difference in Everyday Memory
      Questionnaire -23.9 vs 4.4 (p < 0.001), Logical Memory (Paragraph recall) test
      22.3 vs 0.7 (p < 0.001), Trail Making Test A -7.5 vs -2.6 (p < 0.001), Trail
      Making Test B -10.5 vs -3.1 (p < 0.001), Controlled Oral Word Association Test
      4.2 vs 0.5 (p < 0.001), Hooper test 2.6 vs 0.1 (p < 0.05), Judgement of line
      orientation 2.8 vs 0.3 (p < 0.001), Digit Cancellation time -24.5 vs -2.4 (p <
      0.001), NH4+ 30.5 vs 13.5 (p < 0.001), prothrombin time 2 vs 2.4 (p < 0.05),
      alanine transaminase -10.7 vs -13.6 (p < 0.001). 88% of patients treated with ALC
      vs 72% of patients treated with placebo showed a significant improvement in EEG.
      The improvement of cognitive deficits, the reduction of ammonia, and the
      modification of EEG in patients treated with ALC suggest that ALC could represent
      a new tool in the treatment of severe hepatic encephalopathy.

PMID- 21870122
TI  - Identification of fibrinogen-binding proteins of Aspergillus fumigatus using
      proteomic approach.
AB  - Aspergillus fumigatus, the main etiological agent for various forms of human
      aspergillosis, gets access to the respiratory system of human host by inhalation
      of airborne conidia. These conidia possibly adhere to extracellular matrix (ECM)
      proteins. Among the ECM proteins involved in adherence, fibrinogen is thought to
      be crucial. Here, we studied whether A. fumigatus three-week culture filtrate
      (3wcf) proteins promote binding of A. fumigatus to ECM proteins and promote
      fungal growth. We observed that incubation of ECM with 3wcf proteins led to dose-
      and time-dependent increase in adherence of conidia to the ECM. In order to
      identify the catalogue of fibrinogen-binding A. fumigatus proteins, we carried
      out fibrinogen affinity blotting using two-dimensional gel electrophoresed 3wcf
      proteins. A total of 15 fibrinogen-binding protein spots corresponding to 7
      unique proteins were identified in 3wcf using matrix-assisted laser
      desorption/ionization-time of flight (MALDI-TOF-TOF). Among these, 4 proteins,
      namely, beta-glucosidase, alpha-mannosidase, pectate lyase A and oryzin precursor
      were predicted to have cell wall or extracellular localization, whereas amidase
      family protein and two hypothetical proteins did not display the signal sequence.
      This study reports seven novel fibrinogen-binding proteins of A. fumigatus, some
      of which could be further explored for targeting the adhesion phenomenon as
      antifungal strategy.

PMID- 21870123
TI  - Cloning and characterization of a heme oxygenase-2 gene from alfalfa (Medicago
      sativa L.).
AB  - Heme oxygenase (HO, EC 1.14.99.3) catalyzes the oxidation of heme and performs
      vital roles in plant development and stress responses. Two HO isozymes exist in
      plants. Between these, HO-1 is an oxidative stress-response protein, and HO-2
      usually exhibited constitutive expression. Although alfalfa HO-1 gene (MsHO1) has
      been investigated previously, HO2 is still poorly understood. In this study, we
      report the cloning and characterization of HO2 gene, MsHO2, from alfalfa (Medica
      sativa L.). The full-length cDNA of MsHO2 contains an ORF of 870 bp and encodes
      for 290 amino acid residues with a predicted molecular mass of 33.3 kDa. Similar
      to MsHO1, MsHO2 also appears to have an N-terminal transit peptide sequence for
      chloroplast import. Many conserved residues in plant HO were also conserved in
      MsHO2. However, unlike HO-1, the conserved histidine (His) required for heme-iron
      binding and HO activity was replaced by tyrosine (Tyr) in MsHO2. Further
      biochemical activity analysis of purified mature MsHO2 showed no HO activity,
      suggesting that MsHO2 may not be a true HO in nature. Semi-quantitative RT-PCR
      confirmed its maximum expression in the germinating seeds. Importantly, the
      expression levels of MsHO2 were up-regulated under sodium nitroprusside (SNP) and
      H(2)O(2) (especially) treatment, respectively.

PMID- 21870124
TI  - Surface interactions and fouling properties of Micrococcus luteus with
      microfiltration membranes.
AB  - This study was conducted to investigate microbial adhesion of Micrococcus luteus
      to polypropylene (PP) and polyvinylidene fluoride (PVDF) membranes in relation to
      the variation of the interfacial energies in the membrane-bacteria systems, for
      revealing effects of short-range surface interactions on filtration behavior.
      Both the membranes and M. luteus showed typical strong electron donors and
      hydrophilic properties. The AB component was dominant in the interfacial energies
      of the two membrane-bacteria systems. M. luteus presented larger negative
      U(mlb)(XDLVO) to the PP membrane than to the PVDF membrane. The adhesion
      experiments also proved that M. luteus had higher adhesion percentage to the PP
      membrane. This study demonstrated that the adhesion potentials of M. luteus to
      the PP and PVDF membranes might be explained in terms of bacterium, membrane, and
      intervening medium surface properties, which are mainly determined by the
      interfacial energies in the systems according to the XDLVO theory.

PMID- 21870125
TI  - Optimization of a multiplex PCR assay for detecting transgenic soybean components
      in feed products.
AB  - A multiplex polymerase chain reaction (m-PCR) assay was developed for the
      simultaneous detection of multiple components of genetically modified (GM)
      soybean. It uses two sets of primers (I, lectin1/35S/CP4; II, lectin2/35S/CP4)
      specific for a soybean reference gene, the 35S promoter, and an event-specific
      gene. Amplified fragments of 118, 414, 195, and 320 bp were easily detected by
      agarose gel electrophoresis and were positively confirmed by sequencing. Primer
      set concentrations and annealing temperatures in the m-PCR were optimized. The
      optimized m-PCR conditions were obtained for primer set I at a ratio of 1:2:3 and
      a 59.2  degrees C annealing temperature and set II at the same ratio and 58.6 
      degrees C, 60.3  degrees C, and 61.2  degrees C annealing temperatures. The
      sensitivities of the two m-PCR primer sets (I and II) were 0.25% and 0.5%,
      respectively. The results showed that this m-PCR assay provides rapid, reliable,
      and effective identification of multiple components of GM soybean in feed.

PMID- 21870126
TI  - Cloning and sequence analysis of novel DNA polymerases from thermophilic
      Geobacillus species isolated from hot springs in Turkey: characterization of a
      DNA polymerase I from Geobacillus kaue strain NB.
AB  - The complete coding sequences of the polA genes from seven thermophilic
      Geobacillus species, isolated from hot springs of Gonen and Hisaralan in Turkey,
      were cloned and sequenced. The polA genes of these Geobacillus species contain a
      long open reading frame of 2,637 bp encoding DNA polymerase I with a calculated
      molecular mass of 99 kDa. Amino acid sequences of these Geobacillus DNA
      polymerases are closely related. The multiple sequence alignments show all
      include the conserved amino acids in the polymerase and 5'-3' exonuclease
      domains, but the catalytic residues varied in 3'-5' exonuclease domain of these
      Geobacillus DNA polymerases. One of them, DNA polymerase I from Geobacillus kaue
      strain NB (Gkaue polI) is purified to homogeneity and biochemically characterized
      in vitro. The optimum temperature for enzymatic activity of Gkaue polI is 70 
      degrees C at pH 7.5-8.5 in the presence of 8 mM Mg(2+) and 80-100 mM of
      monovalent ions. The addition of polyamines stimulates the polymerization
      activity of the enzyme. Three-dimensional structure of Gkaue polI predicted using
      homology modeling confirmed the conservation of all the functionally important
      regions in the polymerase active site.

PMID- 21870127
TI  - Effects of low-level laser therapy (808 nm) on isokinetic muscle performance of
      young women submitted to endurance training: a randomized controlled clinical
      trial.
AB  - Low-level laser therapy (LLLT) has shown efficacy in muscle bioenergetic
      activation and its effects could influence the mechanical performance of this
      tissue during physical exercise. This study tested whether endurance training
      associated with LLLT could increase human muscle performance in isokinetic
      dynamometry when compared to the same training without LLLT. The primary
      objective was to determine the fatigue index of the knee extensor muscles (FIext)
      and the secondary objective was to determine the total work of the knee extensor
      muscles (TWext). Included in the study were 45 clinically healthy women (21 +/-
      1.78 years old) who were randomly distributed into three groups: CG (control
      group), TG (training group) and TLG (training with LLLT group). The training for
      the TG and TLG groups involved cycle ergometer exercise with load applied to the
      ventilatory threshold (VT) for 9 consecutive weeks. Immediately after each
      training session, LLLT was applied to the femoral quadriceps muscle of both lower
      limbs of the TLG subjects using an infrared laser device (808 nm) with six 60-mW
      diodes with an energy of 0.6 J per diode and a total energy applied to each limb
      of 18 J. VT was determined by ergospirometry during an incremental exercise test
      and muscle performance was evaluated using an isokinetic dynamometer at 240
      degrees /s. Only the TLG showed a decrease in FIext in the nondominant lower limb
      (P = 0.016) and the dominant lower limb (P = 0.006). Both the TLG and the TG
      showed an increase in TWext in the nondominant lower limb (P < 0.001 and P =
      0.011, respectively) and in the dominant lower limb (P < 0.000 and P < 0.000,
      respectively). The CG showed no reduction in FIext or TWext in either lower limb.
      The results suggest that an endurance training program combined with LLLT leads
      to a greater reduction in fatigue than an endurance training program without
      LLLT. This is relevant to everyone involved in sport and rehabilitation.

PMID- 21870128
TI  - Real-time elastography for the differentiation of benign and malignant breast
      lesions: a meta-analysis.
AB  - The prognostic significance of ultrasound real-time elastography (RTE) in
      patients with breast lesions is controversial. There are two different diagnostic
      methods: the elasticity score (ES) and the strain ratio (SR). A meta-analysis was
      performed using a random-effect model to assess the overall sensitivity and
      specificity of RTE in the differentiation of breast lesions. MEDLINE, EMBASE,
      PubMed, and the Cochrane Library before February 2011 were searched. A total of
      22 studies, which included 4,713 breast nodules in 4,266 patients were analyzed.
      The overall mean sensitivity and specificity for the diagnosis of malignant
      breast lesions by RTE were 0.834 [95% confidence interval (CI) 0.814-0.853] and
      0.842 (95% CI, 0.829-0.854) for ES, and 0.883 (95% CI, 0.844-0.916) and 0.814
      (95% CI, 0.786-0.839) for SR, respectively. RTE has a high sensitivity and
      specificity in the evaluation of breast lesions and can potentially reduce
      unnecessary breast biopsies.

PMID- 21870129
TI  - Invasive lobular carcinoma: response to neoadjuvant letrozole therapy.
AB  - Invasive lobular cancer (ILC) responds poorly to neoadjuvant chemotherapy but
      appears to respond well to endocrine therapy. We examined the effectiveness of
      neoadjuvant letrozole in postmenopausal women (PMW) with estrogen receptor (ER)
      rich ILC. PMW were considered for treatment with neoadjuvant letrozole if they
      had ER-rich, large operable, or locally advanced cancers, or were unfit for
      surgical therapy. Tumor volume was estimated at diagnosis and at 3 months using
      calipers (clinical), ultrasound, and mammography. At 3 months, if physically fit,
      women were assessed for surgery. Responsive women with cancers too large for
      breast-conserving surgery continued with letrozole. Patients had surgery or were
      switched to alternative therapy if tumor volume was increasing. Sixty-one
      patients (mean age, 76.2 years) with 63 ILCs were treated with letrozole for >= 3
      months. The mean reduction in tumor volume at 3 months was 66% (median, 76%)
      measured clinically, 61% (median, 73%) measured by ultrasound, and 54% (median,
      60%) measured by mammography. Surgery was possible at 3 months in 24 cancers in
      24 patients, and all but two of the remaining patients continued with letrozole
      therapy for a median duration of 9 months. At the time of this publication, 40
      patients with a total of 41 cancers have undergone surgery. The rate of
      successful breast conservation was 81% (25/31). Twenty-one patients have
      continued with letrozole monotherapy, and 19 remain controlled on letrozole at a
      median of 2.8 years. There is a high rate of response to letrozole in PMW with ER
      rich ILC.

PMID- 21870130
TI  - Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal
      women.
AB  - Elevated levels of circulating estrogens and androgens are linked to higher
      breast cancer risk among postmenopausal women; however, little is known about
      hormone levels within the breast. Hormone concentrations within the breast may
      not be reflected in the blood and are likely important contributors to breast
      carcinogenesis. We used a previously validated method to measure levels of
      estrone, estradiol, androstenedione, and testosterone in adipose tissue removed
      as part of breast excisions performed for cancer in 100 postmenopausal women (69
      ER/PR +/+ and 31 ER/PR -/-) participating in a breast cancer case-control study.
      We also measured the same steroid hormones, as well as estrone sulfate, and sex
      hormone-binding globulin (SHBG) in serum from these patients and 100 controls
      matched on ages at blood collection and on menopause. Overall, concentrations of
      serum hormones did not vary significantly between controls and cases. However,
      women with ER-/PR- breast cancers had lower circulating levels of all measured
      sex steroid hormones and higher SHBG levels than women with ER+/PR+ breast
      cancers and controls. Similarly, hormone concentrations in breast adipose tissue
      were higher among women with ER+/PR+ compared to ER-/PR- breast cancer, although
      differences were only significant for testosterone. These data demonstrate that
      high sex steroid concentrations in both serum and adipose tissues are more
      strongly related to ER+/PR+ than ER-/PR- breast cancers. Measurement of sex
      hormones in serum and in the microenvironment may help in understanding the
      hormonal etiology of breast cancer, suggest methods for prevention, and have
      value in gauging treatment response and prognosis.

PMID- 21870131
TI  - Purkinje cell-specific ablation of Cav2.1 channels is sufficient to cause
      cerebellar ataxia in mice.
AB  - The Cacna1a gene encodes the alpha(1A) subunit of voltage-gated Ca(V)2.1 Ca(2+)
      channels that are involved in neurotransmission at central synapses. Ca(V)2.1
      alpha(1)-knockout (alpha1KO) mice, which lack Ca(V)2.1 channels in all neurons,
      have a very severe phenotype of cerebellar ataxia and dystonia, and usually die
      around postnatal day 20. This early lethality, combined with the wide expression
      of Ca(V)2.1 channels throughout the cerebellar cortex and nuclei, prohibited
      determination of the contribution of particular cerebellar cell types to the
      development of the severe neurobiological phenotype in Cacna1a mutant mice. Here,
      we crossed conditional Cacna1a mice with transgenic mice expressing Cre
      recombinase, driven by the Purkinje cell-specific Pcp2 promoter, to specifically
      ablate the Ca(V)2.1-alpha(1A) subunit and thereby Ca(V)2.1 channels in Purkinje
      cells. Purkinje cell Ca(V)2.1-alpha(1A)-knockout (PCalpha1KO) mice aged without
      difficulties, rescuing the lethal phenotype seen in alpha1KO mice. PCalpha1KO
      mice exhibited cerebellar ataxia starting around P12, much earlier than the first
      signs of progressive Purkinje cell loss, which appears in these mice between P30
      and P45. Secondary cell loss was observed in the granular and molecular layers of
      the cerebellum and the volume of all individual cerebellar nuclei was reduced. In
      this mouse model with a cell type-specific ablation of Ca(V)2.1 channels, we show
      that ablation of Ca(V)2.1 channels restricted to Purkinje cells is sufficient to
      cause cerebellar ataxia. We demonstrate that spatial ablation of Ca(V)2.1
      channels may help in unraveling mechanisms of human disease.

PMID- 21870132
TI  - [Fractures of the distal humerus in the elderly. Pros and cons of endoprosthetic
      replacement].
AB  - The intraarticular fracture of the distal humerus in an elderly patient remains a
      challenge for trauma surgeons. In case of severe co-morbidities and/or
      osteoporosis stable fixation with screws and plates is difficult and in some
      cases can be impossible. Even if osteosynthesis is feasible the clinical outcome
      is still incalculable due to delayed or non-union of the fracture fragments.
      Endoprosthetic replacement of the elbow joint for comminuted distal humerus
      fractures has been used for almost 20 years. The clinical results are
      predominantly excellent or good and better predictable than those of
      osteosynthesis. There still is no guideline when a prosthesis for the elbow joint
      should be used. We reviewed the literature and outline the current
      recommendations for diagnostics and surgical therapy for distal humerus fractures
      in the elderly.

PMID- 21870134
TI  - [Teamwork and leadership in the trauma room. Trauma room management from a
      psychological perspective].
AB  - The treatment of patients in the trauma room places extraordinary demands on the
      multidisciplinary and multiprofessional team with regard to expert qualifications
      and teamwork. The present study triangulates data extracted from observation,
      interviews and questionnaires. In general, team climate and teamwork are good,
      yet some problems could be identified. Not all team members-especially younger
      physicians and nurses-feel free to express their doubts and uncertainties.
      Furthermore, the treatment plan is not always clear for all team members. Absent
      or unclear leadership is seen as a main problem when a treatment proceeds
      negatively. The establishment of a team leader is therefore recommended.

PMID- 21870133
TI  - [Templating and radiological outcome monitoring for elective total hip
      arthroplasty. Applied quality management principles for safe patient care].
AB  - Implementation of total hip arthroplasty is a successful and reliable treatment
      for end-stage osteoarthritis. The biomechanics and components as well as the
      fixation were selected with the aid of templating. Based on a cohort of 114
      patients the quality of digital X-rays and the operative results were determined.
      There was a slight leg lengthening and a good offset reconstruction in these
      patients. For the patients with replacement of the second hip the leg lengthening
      was smaller. The cup inclination was at 43 degrees  and 44 degrees  within the
      desired range. The prediction of the exact component size used was 40% for the
      cup and 29% for the stem.Through variation in scaling of the digital X-ray a
      diminishing prediction accuracy was found in our study. The correction of
      biomechanics and position of components showed good quality in patient care.
      Templating and assessment of the postoperative result in total hip arthroplasty
      is a model for continuous quality management and can be recommended for safe
      patient care.

PMID- 21870135
TI  - Phonotactic probability of brand names: I'd buy that!
AB  - Psycholinguistic research shows that word-characteristics influence the speed and
      accuracy of various language-related processes. Analogous characteristics of
      brand names influence the retrieval of product information and the perception of
      risks associated with that product. In the present experiment we examined how
      phonotactic probability-the frequency with which phonological segments and
      sequences of segments appear in a word-might influence consumer behavior.
      Participants rated brand names that varied in phonotactic probability on the
      likelihood that they would buy the product. Participants indicated that they were
      more likely to purchase a product if the brand name was comprised of common
      segments and sequences of segments rather than less common segments and sequences
      of segments. This result suggests that word-characteristics may influence higher
      level cognitive processes, in addition to language-related processes.
      Furthermore, the benefits of using objective measures of word characteristics in
      the design of brand names are discussed.

PMID- 21870136
TI  - Non-uniform decay in jumping exercise-induced bone gains following 12 and 24
      weeks of cessation of exercise in rats.
AB  - The effects of deconditioning on exercise-induced bone gains in rats were
      investigated in 12-week-old female WKY rats performing a standard jumping
      exercise regimen for either 8, 12 or 24 weeks, followed by sedentary periods of
      either 24, 12 or 0 weeks, respectively. Age-matched controls received no exercise
      over the same period. At the end of the training/sedentary period, the tibiae
      were harvested for analyses of bone parameters. Gains in tibial fat-free dry
      weight decayed within 12 weeks of deconditioning, but gains in tibial ultimate
      bending force (strength), maximum diameter and cortical area were still present
      at 12 weeks of deconditioning. With the exception of cortical area, all other
      exercise-induced bone gains decayed by the 24th week of deconditioning. It
      appears that the decay in exercise-induced bone gains in strength, physical and
      morphological properties is not uniform, and that gains in fat-free dry weight
      seem to decay earlier.

PMID- 21870137
TI  - Effects of suppressing the DNA mismatch repair system on homeologous
      recombination in tomato.
AB  - In plant breeding, the ability to manipulate genetic (meiotic) recombination
      would be beneficial for facilitating gene transfer from wild relatives of crop
      plants. The DNA mismatch repair (MMR) system helps maintain genetic integrity by
      correcting base mismatches that arise via DNA synthesis or damage, and
      antagonizes recombination between homeologous (divergent) DNA sequences. Previous
      studies have established that the genomes of cultivated tomato (Solanum
      lycopersicum) and the wild relative S. lycopersicoides are substantially diverged
      (homeologous) such that recombination between their chromosomes is strongly
      reduced. Here, we report the effects on homeologous recombination of suppressing
      endogenous MMR genes in S. lycopersicum via RNAi-induced silencing of SlMSH2 and
      SlMSH7 or overexpressing dominant negatives of Arabidopsis MSH2 (AtMSH2-DN) in an
      alien substitution line (SL-8) of S. lycopersicoides in tomato. We show that
      certain inhibitions of MMR (RNAi of SlMSH7, AtMSH2-DN) are associated with modest
      increases in homeologous recombination, ranging from 3.8 to 29.2% (average rate
      of 17.8%) compared to controls. Unexpectedly, only the AtMSH2-DN proteins but not
      RNAi-induced silencing of MSH2 was found to increase homeologous recombination.
      The ratio of single to double crossovers (SCO:DCO ratio) decreased by
      approximately 50% in progeny of the AtMSH2-DN parents. An increase in the
      frequency of heterozygous SL-8 plants was also observed in the progeny of the
      SlMSH7-RNAi parents. Our findings may contribute to acceleration of introgression
      in cultivated tomato.

PMID- 21870138
TI  - Coronary risk assessment in patients with HIV infection: why bother?

PMID- 21870139
TI  - Does Helicobacter pylori infection protect against esophageal diseases in Asia?
AB  - The speculations on the protective role of Helicobacter pylori against
      gastroesophageal reflux disease (GERD) originated from epidemiological
      observations. These studies have shown that the rising trend of GERD is
      coincident with declining prevalence of H. pylori and peptic ulcer disease in
      Asia. Furthermore, most case-control and population-based studies suggest a
      negative association between H. pylori infection and GERD. It is generally
      believed that the preponderance of cagA+ and vacA+ virulent strains and
      proinflammatory interleukin-1 beta polymorphism increase the risk of
      hypochlohydria and protects against the development of GERD in Asian population.
      Recovery of gastric acid secretion and emergence of reflux esophagitis has been
      reported after H. pylori eradication in patients with corpus gastritis and
      atrophic gastritis. Recent studies have also reported that H. pylori eradication
      leads to recovery of ghrelin secreting cells in the gastric corpus and a rise in
      plasma ghrelin levels, which may contribute to obesity through its appetite
      stimulating action and predispose to GERD. The prevalence of H. pylori infection
      is generally lower in younger Asians who enjoy improved socioeconomic status and
      sanitation compared with their older counterparts. The Asian population is
      probably facing a rising generation with high gastric acid and ghrelin secretion
      rates. These physiological changes may contribute to increased dietary calorie
      intake, obesity and increased prevalence of GERD.

PMID- 21870140
TI  - The implementation of tissue banking experiences for setting up a cGMP cell
      manufacturing facility.
AB  - Cell manufacturing for clinical applications is a unique form of biologics
      manufacturing that relies on maintenance of stringent work practices designed to
      ensure product consistency and prevent contamination by microorganisms or by
      another patient's cells. More extensive, prolonged laboratory processes involve
      greater risk of complications and possibly adverse events for the recipient, and
      so the need for control is correspondingly greater. To minimize the associate
      risks of cell manufacturing adhering to international quality standards is
      critical. Current good tissue practice (cGTP) and current good manufacturing
      practice (cGMP) are examples of general standards that draw a baseline for cell
      manufacturing facilities. In recent years, stem cell researches have found great
      public interest in Iran and different cell therapy projects have been started in
      country. In this review we described the role of our tissue banking experiences
      in establishing a new cGMP cell manufacturing facility. The authors concluded
      that, tissue banks and tissue banking experts can broaden their roles from
      preparing tissue grafts to manufacturing cell and tissue engineered products for
      translational researches and phase I clinical trials. Also they can collaborate
      with cell processing laboratories to develop SOPs, implement quality management
      system, and design cGMP facilities.

PMID- 21870141
TI  - [Guide values for heart rate and blood pressure with reference to 20, 40, 60 und
      80% of maximum exertion considering age, sex and body mass in non-trained
      individuals].
AB  - Aim of this study was to evaluate reliable guide values for heart rate (HF) and
      blood pressure (RR) with reference to defined sub maximum exertion considering
      age, gender and body mass. One hundred and eighteen healthy but non-trained
      subjects (38 women, 80 men) were included in the study. For interpretation,
      finally facts of 28 women and 59 men were used. We found gender differences for
      HF and RR. Further, we noted significant correlations between HF and age as well
      as between RR and body mass at all exercise levels. We established formulas for
      gender-specific calculation of reliable guide values for HF and RR on sub maximum
      exercise levels.

PMID- 21870142
TI  - The role of osteoprotegerin (OPG) receptor activator for nuclear factor kappaB
      ligand (RANKL) in cardiovascular pathology - a review.
AB  - Initially described as key regulators in metabolic bone disease osteoprotegerin
      (OPG), receptor activator of nuclear factor kappa B (RANK) and RANK ligand
      (RANKL) have also been discriminated as regulators in immunologic function.
      Cardiovascular diseases (CVD) develop over many years in life and are often
      triggered by inflammatory processes within the vessel wall that lead to vascular
      remodeling. Recently some study groups have described OPG as a prognostic
      parameter for mortality and morbidity in cardiovascular patients.

PMID- 21870143
TI  - Acute renal artery aneurysm rupture - a rare differential diagnosis of acute
      appendicitis.
AB  - A 50-year-old patient with symptoms of an acute appendicitis turns out to be
      suffering of a life threatening rupture of a renal artery aneurysm. We performed
      an emergency operation with the resection of this aneurysm. An imminent
      hemorrhagic shock made a targeted intensive medical therapy necessary.

PMID- 21870144
TI  - Magnitude of zinc deficiency and efficacy of zinc.

PMID- 21870145
TI  - Non-traumatic coma and altered mental status.
AB  - Non traumatic coma in childhood is an important emergency. It can result from
      wide range of etiologies. CNS infections are the most common cause of non
      traumatic coma in children. However, multiple interrelated factors may be present
      in one patient. Management of a comatose child goes hand in hand with clinical
      evaluation. It is an emergency that requires simultaneous institution of
      immediate life support, identification of the cause and institution of definite
      therapy. The primary goal is to establish airway, breathing and circulation and
      to identify and treat raised intracranial pressure and seizures.

PMID- 21870146
TI  - Effect of oxidative stress on membrane proteins in thalassemia and iron
      deficiency anemia.
AB  - OBJECTIVE: To evaluate the effect of oxidative stress on membrane proteins
      according to relationship between malondialdehyde (MDA) levels and membrane
      protein ratios in different two patient groups. METHODS: Fifty-seven healthy
      control cases that had no symptoms of inherited blood diseases, 50 diagnosed beta
      thalassemic patients, and 30 patients with iron deficiency anemia were enrolled.
      Erythrocyte membrane samples were prepared according to Dodge method and proteins
      were separated using 8.3% SDS-PAGE. Gels were stained with Coomassie Brillant
      Blue, then fraction quantities were determined by dansitometric method. MDA
      levels were measured by thiobarbituric acid method in plasma. One-way ANOVA test
      was used to compare parameters between groups. RESULTS: Significant difference in
      protein deficiency rates for spectrin and band 4.2 in group I, band 6 in group II
      and band 3 in group I and II when compared with control group (group III) were
      found. The significant difference between group I and II wasn't determined in
      spite of the fact that MDA levels of patients were different from the control
      group statistically. CONCLUSIONS: Any significant relationship statistically was
      not found. This consequence may be due to priority removal of oxidatively injured
      cells from the circulation in thalassemic patients and therefore, significant
      increase wasn't determined in the concentration of MDA.

PMID- 21870147
TI  - Decline of the medical history and physical examination.

PMID- 21870148
TI  - Importance of low blood pH in diabetic ketoacidosis.

PMID- 21870149
TI  - Dietary restriction regulates brain acetylcholinesterase in female mice as a
      function of age.
AB  - In the present study, the normal endogenous activity level of
      acetylcholinesterase (AChE) was investigated in cerebral hemispheres and
      cerebellum of female mice as a function of age. The effects of 24-h fasting and
      refeeding, and dietary restriction (DR) on AChE activity and its protein
      expression patterns were also investigated in young (1-month) and old (18-month)
      mice. Our results show that the activity (U/mg protein) and level of AChE protein
      in the cerebral hemispheres of young mice is decreased significantly on 24-h
      fasting which reverses back on refeeding. On the other hand, DR produces an
      accumulative effect; thereby it decreases the activity of this enzyme in the
      cerebral hemispheres of both the young and old mice and the degree of reduction
      is of different magnitude, dictated in an age- and brain region-specific manner.
      Our findings suggest that DR regulates the activity of this enzyme which may be
      useful in related neurodegenerative disease conditions.

PMID- 21870150
TI  - Systematic review of pancreaticoduodenectomy for locally advanced gastric cancer.
AB  - BACKGROUND: The purpose of this study was to identify and synthesize findings
      from all articles on surgical and long-term outcomes in patients with gastric
      cancer undergoing gastrectomy combined with pancreaticoduodenectomy (PD).
      METHODS: Electronic literature searches were conducted using Medline, EMBASE, and
      Cochrane databases from January 1, 1985, to December 31, 2009. RESULTS: Eight
      retrospective case series were included, with 132 patients having PD combined
      with gastrectomy. PD was combined with total gastrectomy in 27 patients, and
      subtotal gastrectomy in 81 patients; 24 patients had undocumented gastric
      resection type. Clinical stage was available for 92 patients (4 stage I, 7 stage
      II, 26 stage III, and 55 stage IV). Five studies (98 patients having PD combined
      with gastrectomy) compared PD and gastrectomy to gastrectomy alone. In the four
      studies reporting morbidity, PD had a higher morbidity. The pooled pancreatic
      anastomotic leak rate was 24.5% for the seven studies in which complications were
      reported; however, there were no peri-operative deaths. Long-term survival (37.3%
      at 5 years) in gastric cancer patients with PD combined with gastrectomy was
      described; however, survival was poor in the setting of incurable factors. Due to
      heterogeneity of patients and staging techniques in the case series no
      recommendations can be made on the appropriate selection criteria for patients
      undergoing PD and gastrectomy. CONCLUSION: PD for gastric cancer invading the
      pancreas is associated with a higher morbidity; given the heterogeneous data,
      defining exact selection criteria is difficult.

PMID- 21870151
TI  - Analysis of trace and major elements in bronchoalveolar lavage fluid of
      Mycoplasma bronchopneumonia in calves.
AB  - The aim of this study was to evaluate the reliability and effectiveness of direct
      determination of trace and major element concentrations in bronchoalveolar lavage
      fluid samples from Holstein calves with Mycoplasma bronchopneumonia (n = 21) and
      healthy controls (n = 20). The samples were obtained during bronchoscopy using a
      standard examination method. A total of 18 elements (aluminum, bromine, calcium,
      chlorine, chromium, copper, iron, potassium, magnesium, manganese, molybdenum,
      nickel, phosphorous, sulfur, silicon, strontium, titanium, and zinc) were
      detected by particle-induced X-ray emission. The average bromine, iron,
      potassium, magnesium, and phosphorous concentrations were higher in calves with
      bronchopneumonia than in controls (p < 0.05). They were found to have higher
      amounts of calcium and zinc, and a higher zinc-copper ratio than that in healthy
      calves (p < 0.001). Based on the receiver operating characteristics curves, we
      propose a diagnostic cutoff point for zinc-copper ratio for identification of
      Mycoplasma pneumonia of 8.676. Our results indicate that assessment of the
      elemental composition of broncholaveolar lavage fluid is a promising diagnostic
      tool for Mycoplasma bronchopneumonia.

PMID- 21870152
TI  - Effect of mycophenolate mofetil on plasma bioelements in renal transplant
      recipients.
AB  - The proper concentrations of plasma bioelements may favorably reduce the
      incidence of metabolic disorders, which often occur during immunosuppressive
      therapy. Mycophenolate mofetil (MMF) is currently one of the most frequently
      administered immunosuppressive agents; however, MMF treatment is often related to
      gastrointestinal side effects. The aim of this study was thus to verify whether
      the MMF treatment itself, or its metabolite pharmacokinetics, has an effect on
      the concentrations of plasma bioelements. To determine this, the effect of MMF on
      the levels of both major (sodium [Na], potassium [K], calcium [Ca], magnesium
      [Mg]), and trace (iron [Fe], zinc [Zn], copper [Cu]) plasma bioelements in 61
      renal transplant recipients was assessed in comparison to a control group (n =
      45). The pharmacokinetic parameters of mycophenolic acid were determined by the
      high-performance liquid chromatography method. All patients filled out a 24-h
      diet history questionnaire. The results showed high plasma concentrations of Fe
      and low plasma concentrations of Mg and Zn as compared with diagnostic norms. The
      patients treated with MMF had significantly lower plasma Na (P < 0.001) and
      significantly higher plasma Zn (P = 0.030) and Cu concentrations (P < 0.001). In
      conclusion, MMF treatment was found to affect plasma Fe, Zn, and Cu levels by
      increasing their concentrations while decreasing the plasma Na concentration. Mg
      and Zn deficiencies, as well as excessive Fe levels, are frequently observed
      irrespective of the immunosuppressive regimen applied, which suggests that
      monitoring of these bioelements may be favorable.

PMID- 21870153
TI  - Correlations of trace element levels in the diet, blood, urine, and feces in the
      Chinese male.
AB  - In order to explore the associations between trace elements in dietary intake and
      the other three biological media (blood, urine, or feces) and inter-element
      interactions among the latter, we simultaneously collected 72-h diet duplicates,
      whole blood, and 72-h urine and feces from 120 free-living healthy males in
      China. Correlations among the toxic (cadmium [Cd], lead [Pb]), and nutritionally
      essential (zinc [Zn], copper [Cu], iron [Fe], manganese [Mn], selenium [Se],
      iodine [I]) elements were evaluated using Spearman rank correlation analysis
      based on analytical data determined by inductively coupled plasma-mass
      spectrometry. Dietary Cd intakes were highly correlated with the fecal Cd and
      blood Cd levels. Inverse correlations were found for Fe-Cd and Fe-Pb in both diet
      versus blood and diet versus feces. Cd-Zn and Cd-Se were significantly directly
      correlated in the urine and feces. Cd-Se and Pb-Se were negatively correlated in
      blood. In addition, there existed an extremely significant association between
      urinary Se and urinary I. Moreover, the other two highly direct correlations were
      found for Se-Fe and for I-Fe in urine. Improved knowledge regarding their mutual
      associations is considered to be of fundamental importance to understand more the
      complex interrelationships in trace element metabolism.

PMID- 21870154
TI  - Caffeic acid phenethyl ester modulates gentamicin-induced oxidative
      nephrotoxicity in kidney of rats.
AB  - In this study, the modulator effect of caffeic acid phenethyl ester (CAPE) on the
      oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by
      determining indices of lipid peroxidation and the activities of antioxidant
      enzymes as well as by histological analyses. Forty female Wistar albino rats were
      randomly divided into four groups, namely control, gentamicin, CAPE, and
      gentamicin plus CAPE. On the 12th day of the study, all rats were sacrificed and
      then blood samples and kidneys were taken. Lipid peroxidation and nitric oxide
      levels, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase
      (CAT) enzyme activities, and histological evaluation were measured in kidneys of
      rats. Levels of blood urea nitrogen and creatinine were studied in serum. CAPE
      with gentamicin caused decreases in lipid peroxidation, nitric oxide, urea
      nitrogen, and creatinine levels, although it caused increases in CAT, GSH-Px, and
      SOD activities when compared with gentamicin alone. In addition, on histological
      evaluation, the renal damage caused by gentamicin alone appeared much higher than
      that caused by CAPE plus gentamicin. It is concluded that oxidative stress plays
      a critical role in causing gentamicin nephrotoxicity and that this nephrotoxicity
      may be significantly reduced by CAPE.

PMID- 21870155
TI  - Activity and expression of enkephalinase and aminopeptidase N in regions of the
      mesocorticolimbic system are selectively modified by acute ethanol
      administration.
AB  - Opioid peptides play a key role in ethanol reinforcement and alcohol drinking
      behavior. However, regulation of opioid levels by peptidase-degrading activities
      in ethanol's actions in brain is still unclear. The aim of this work was to study
      the acute effects of ethanol (2.5 g/kg) on enkephalinase (NEP) and aminopeptidase
      N (APN) activities and expression in regions of the mesocorticolimbic system, as
      well as on corticosterone levels in serum for up to 24 h after administration.
      Enzymatic activities were measured by fluorometric assays, mRNA's expression by
      reverse transcriptase polymerase chain reaction (RT-PCR) and corticosterone
      levels by radioimmunoassay. Acute ethanol administration modified peptidase
      activity and expression with different kinetics. Ethanol induced a transitory
      increase and decrease in NEP and APN activities in the frontal cortex (FC) and
      ventral tegmental area (VTA), whereas only increases in these activities were
      observed in the nucleus accumbens (NAcc). Ethanol induced an increase in NEP mRNA
      in the FC and decreases in APN mRNA in the FC and NAcc. In contrast, ethanol
      produced biphasic effects on both enzymes expression in the VTA. Corticosterone
      levels were not changed by ethanol. Our results suggest that NEP and APN could
      play a main role in ethanol reinforcement through regulation of opioid levels in
      mesolimbic areas.

PMID- 21870156
TI  - A genetic linkage map and comparative genome analysis of common carp (Cyprinus
      carpio L.) using microsatellites and SNPs.
AB  - A genetic linkage map is a powerful research tool for mapping traits of interest
      and is essential to understanding genome evolution. The aim of this study is to
      provide an expanded genetic linkage map of common carp to effectively carry out
      quantitative trait loci analysis and conduct comparative mapping analysis between
      lineages. Here, we constructed a genetic linkage map of common carp (Cyprinus
      carpio L.) using microsatellite and single-nucleotide polymorphism (SNP) markers
      in a 159 sibling family. A total of 246 microsatellites and 306 SNP polymorphic
      markers were genotyped in this family. Linkage analysis using JoinMap 4.0
      organized 427 markers (186 microsatellites and 241 SNPs) to 50 linkage groups,
      ranging in size from 1.4 to 130.1 cM. Each group contained 2-30 markers. The
      linkage map covered a genetic distance of 2,039.2 cM and the average interval for
      markers within the linkage groups was approximately 6.4 cM. In addition,
      comparative genome analysis within five model teleost fish revealed a high
      percentage (74.7%) of conserved loci corresponding to zebrafish chromosomes. In
      most cases, each zebrafish chromosome comprised two common carp linkage groups.
      The comparative analysis also revealed independent chromosome rearrangements in
      common carp and zebrafish. The linkage map will be of great assistance in mapping
      genes of interest and serve as a reference to approach comparative mapping and
      enable further insights into the comprehensive investigations of genome evolution
      of common carp.

PMID- 21870158
TI  - Pea aphids, Acyrthosiphon pisum, suppress induced plant volatiles in broad bean,
      Vicia faba.
AB  - Plants defend themselves against herbivory through several means, including the
      production of airborne volatile organic compounds (VOCs). These VOCs benefit
      plants by attracting natural enemies of their herbivores. The pea aphid,
      Acyrthosiphon pisum, is able to feed on its host plant, Vicia faba, without
      inducing detectable changes in plant VOC emission. Levels of VOCs emission are
      not significantly different between control plants and those fed upon by aphids
      for up to 5 days. Using a second herbivore, the beet armyworm caterpillar,
      Spodoptera exigua, we demonstrate that several expected caterpillar-induced VOCs
      are reduced when co-infested with pea aphids, thus demonstrating that pea aphids
      have the ability to inhibit the release of certain VOCs. This study shows, for
      the first time, that aphids not only avoid triggering plant volatile emission,
      but also can actively inhibit herbivore-induced volatiles.

PMID- 21870159
TI  - Biodegradation of soil-applied pesticides by selected strains of plant growth
      promoting rhizobacteria (PGPR) and their effects on bacterial growth.
AB  - A laboratory study was conducted to investigate the influence of four PGPR
      strains on the degradation of five soil applied pesticides and their effects on
      bacterial growth. Interactions of Bacillus subtilis GB03, Bacillus subtilis
      FZB24, Bacillus amyloliquefaciens IN937a and Bacillus pumilus SE34 with two
      concentrations of acibenzolar-S-methyl, metribuzin, napropamide, propamocarb
      hydrochloride and thiamethoxam in liquid culture and soil microcosm were studied.
      The degradation of acibenzolar-S-methyl by all PGPR tested in low and high
      concentration, was 5.4 and 5.7 times, respectively, faster than that in non
      inoculated liquid culture medium. At the end of the 72-h liquid cultured
      experiments, 8-18, 9-11, 15-36 and 11-22% of metribuzin, napropamide, propamocarb
      hydrochloride and thiamethoxam, respectively, had disappeared from PGPR
      inoculated medium. Under the soil microcosm experimental conditions, the half
      lives of acibenzolar-S-methyl incubated in the presence of PGPR strains spiked at
      1.0 and 10.0 mg kg(-1) were 10.3-16.4 and 9.2-15.9 days, respectively, markedly
      lower compared with >34.2 days in the control. From the rest pesticides studied
      degradation of propamocarb hydrochloride and thiamethoxam was enhanced in the
      presence of B. amyloliquefaciens IN937a and B. pumilus SE34. Acibenzolar-S
      methyl, propamocarb hydrochloride and thiamethoxam significantly increased the
      PGPR growth. However, the stimulatory effect was related to the level of
      pesticide spiked.

PMID- 21870157
TI  - Marijuana exposure opportunity and initiation during college: parent and peer
      influences.
AB  - Marijuana is the most prevalent illicit drug used by adolescents and young
      adults, yet marijuana initiation is rarely studied past adolescence. The present
      study sought to advance our understanding of parent and peer influences on
      marijuana exposure opportunity and incident use during college. A sample of 1,253
      students was assessed annually for 4 years starting with the summer prior to
      college entry. More than one-third (38%(wt)) of students had already used
      marijuana at least once prior to college entry; another 25%(wt) initiated use
      after starting college. Of the 360 students who did not use marijuana prior to
      college, 74% were offered marijuana during college; of these individuals, 54%
      initiated marijuana use. Both low levels of parental monitoring during the last
      year of high school and a high percentage of marijuana-using peers independently
      predicted marijuana exposure opportunity during college, holding constant
      demographics and other factors (AOR = 0.92, 95% CI = 0.88-0.96, p < .001 and AOR
      = 1.11, 95% CI = 1.08-1.14, p < .001, respectively). Among individuals with
      exposure opportunity, peer marijuana use (AOR = 1.04, 95% CI = 1.03-1.05, p <
      .001), but not parental monitoring, was associated with marijuana initiation.
      Results underscore that peer influences operate well into late adolescence and
      young adulthood and thus suggest the need for innovative peer-focused prevention
      strategies. Parental monitoring during high school appears to influence exposure
      opportunity in college; thus, parents should be encouraged to sustain rule
      setting and communication about adolescent activities and friend selection
      throughout high school.

PMID- 21870160
TI  - Phytotreatment of soil contaminated with used lubricating oil using Hibiscus
      cannabinus.
AB  - Soil contamination by hydrocarbons, especially by used lubricating oil, is a
      growing problem in developing countries, which poses a serious threat to the
      environment. Phytoremediation of these contaminated soils offers environmental
      friendly and a cost effective method for their remediation. Hibiscus cannabinus
      was studied for the remediation of soil contaminated with 2.5 and 1% used
      lubricating oil and treated with organic wastes [banana skin (BS), brewery spent
      grain (BSG) and spent mushroom compost (SMC)] for a period of 90 days under
      natural conditions. Loss of 86.4 and 91.8% used lubricating oil was recorded in
      soil contaminated with 2.5 and 1% oil and treated with organic wastes
      respectively at the end of 90 days. However, 52.5 and 58.9% oil loss was recorded
      in unamended soil contaminated with 2.5 and 1% oil, respectively. The plant did
      not accumulate hydrocarbon from the soil but shows appreciable accumulation of Fe
      and Zn in the root and stem of H. cannabinus at the end of the experiment. The
      first order kinetic rate of uptake of Fe and Zn in H. cannabinus was higher in
      organic wastes amendment treatments compared to the unamended treatments, which
      are extremely low. The results of this study suggest that H. cannabinus has a
      high potential for remediation of hydrocarbon and heavy metal contaminated soil.

PMID- 21870161
TI  - Social disparities, communication inequalities, and HIV/AIDS-related knowledge
      and attitudes in India.
AB  - Promoting awareness, increasing knowledge, and eliminating stigma is important
      for stopping the spread of HIV/AIDS. The relation of social determinants and
      communication inequalities with HIV/AIDS-related cognitive processes has not been
      studied previously in India. Gender-stratified Poisson regression models of
      123,459 women and 73,908 men in the 2005-2006 National Family Health Survey were
      used to calculate relative risk estimates and 95% confidence intervals for these
      associations. Results indicated that there are significant inequalities in mass
      media use among different social classes. Education and wealth are strongly and
      positively associated with awareness of HIV/AIDS and knowledge about prevention
      and transmission of AIDS and negatively associated with HIV/AIDS-related stigma.
      These associations attenuated when use of various mass media types were added to
      the models with television showing the strongest effect. Mass media may be
      helpful in reducing social disparities in HIV/AIDS outcomes.

PMID- 21870164
TI  - Assessment of cerebral oxygenation using near infrared spectroscopy during
      isovolemic hemodilution in pediatric patients.
AB  - One means of limiting the need for allogeneic blood transfusions is isovolemic
      hemodilution where blood is removed in the operating room and replaced with
      isotonic fluids to maintain euvolemia. Although the delivery of oxygen to the
      tissues is generally maintained by compensatory physiologic mechanisms, there are
      limited data evaluating tissue oxygenation in actual clinical practice. The
      current study evaluates the effects of isovolemic hemodilution on cerebral
      oxygenation using near-infrared spectroscopy (NIRS). NIRS was monitored and
      isovolemic hemodilution achieved in 12 pediatric patients who ranged in age from
      12 to 16 years. After anesthetic induction, isovolemic hemodilution was carried
      out by phlebotomy and the collection of blood which was replaced with colloid to
      achieve a final hematocrit of 25-30%. There was no statistically significant
      change in heart rate, mean arterial pressure or central venous pressure during
      isovolemic hemodilution. The baseline cerebral oximeter obtained after the
      induction of anesthesia was 81 +/- 8 on the right and 82 +/- 7 on the left. At
      the completion of isovolemic hemodilution, the cerebral saturations were 77 +/-
      10 on the right and 78 +/- 8 on the left. No patient had a decreased in cerebral
      oxygenation of greater than 10 during isovolemic hemodilution. The greatest
      decrease in the cerebral oximeter reading during isovolemic hemodilution was 8.
      Our data provides preliminary evidence supporting the safety of moderate
      isovolemic hemodilution in a pediatric population. We found that cerebral
      oxygenation is well maintained by compensatory mechanisms. Modalities such as
      NIRS to monitor end-organ oxygenation may be particularly valuable in patients
      with co-morbid disease processes which may affect end organ oxygenation or
      prevent the compensatory mechanisms that maintain oxygen delivery during anemia.

PMID- 21870165
TI  - [Medical examination: Preparation for ENT specialisation. Part 1].

PMID- 21870166
TI  - [Discharge of children against medical advice at CHU of Brazzaville (Congo)].
AB  - In a prospective study conducted from January to December 2010 in the Teaching
      Hospital of Brazzaville (Congo), we compared the discharge of hospitalized
      children against medical advice at the parents' request (group 1 - cases) with
      those admitted during same period with routine discharge (group 2 - controls).
      Two hundred and seven (7.7%) hospitalized children, 117 boys and 90 girls, were
      discharged at the parents request. The mean age was 18.0 +/- 13.5 months (range:
      1 month-5 years). Among these patients, 150 (72.5%) children were from biparental
      families, and 30.9% of children were the first and/or only child of the
      household. Among the parents of Congolese nationality, 147 (71%) had a secondary
      school level education, including 66.7% of mothers and 58% of the fathers 59.9%
      of children were admitted between 15 and 7 hours, and 75.4% were hospitalized
      during working days. The duration of hospitalization did not exceed 3 days in 147
      cases (71%). The main reasons for hospitalization were digestive disorders (27%),
      fever (16.4%), convulsions (11.1%) and anaemia (11.1%). Among patients discharged
      against medical advice, 34.8% left on the first day of hospitalization (72
      cases), 36.7% before the start of treatment (76 cases of which 36 during check
      up) and 63.3% during treatment (131 cases). The main reasons for discharge
      request were improvement in the clinical condition improvement (30.9% of cases),
      lack of money (28% of cases), supposed insufficient medical care (7.7% of cases),
      unsatisfactory hospitalization conditions (6.3% of cases), care of other children
      at home (6.3% of cases), traditional and/or religious beliefs (5.8% of cases) and
      disagreements with nurses (5.3%). Patients discharge against medical advice was
      correlated strongly with the educational level of parents, age of the child,
      delay of consultation, time of admission, rank of the child in family and
      nationality of parents. Discharge against medical advice is associated to the
      distrust between the patients and nurses. Improvement of hospitalization
      conditions in our hospitals, improvement of the socioeconomic status of Congolese
      and establishment of national social security seem to be the main determinants of
      reduction of discharge against medical advice.

PMID- 21870167
TI  - [Current profile of HIV-infected patients hospitalized in Dakar (Senegal)].
AB  - Ten years after the introduction of the Senegalese Antiretroviral Drug Access
      Initiative in 1998, we conducted a retrospective study of the epidemiological and
      clinical profiles and outcome of HIV-infected patients hospitalized in the
      Infectious Diseases Clinic of Fann Teaching Hospital in Dakar between 2007 and
      2008. During these 2 years, 527 HIV-positive patients were included. The average
      age of the patients was 41 +/- 10 years, and the sex-ratio (F/M) was 1.1; 56% of
      patients were married. The average interval before admission was 40 +/- 57 days.
      Fever (83%), loss of weight (83%) and cough (54%) were the principal symptoms.
      Tuberculosis (40.9%) and gastrointestinal candidiasis (38.9%) were the commonest
      opportunistic infections. Most patients were diagnosed at the AIDS stage (88%)
      and the CD4+ T lymphocyte count was <= 200/mm3 in 86% of cases. Hospital fatality
      was 44% (231/527). Tuberculosis (36%), bacterial pneumonia (18%) and encephalitis
      (12%) were the most frequent causes of death. Despite the availability of and
      free access to antiretroviral drugs in Senegal, the mortality associated with HIV
      infection remains very high due to late diagnosis. The population must be
      educated to boost early screening and care.

PMID- 21870168
TI  - [Presumptive clinical diagnosis of malaria in children in a hospital in the North
      Region (Cameroon)].
AB  - The authors studied the correlation between the prescription of antimalarial
      drugs and the results of a rapid diagnostic test (RDT) and thick smear during dry
      and rainy seasons in a regional hospital outpatient clinic in North Cameroon.
      Clinical diagnosis, essentially based on the presence of fever, has a positive
      predictive value of 2% when compared with laboratory results during the dry
      season, against 44% during the rainy season. This study confirms the epidemic
      nature of malaria in the Sahelian zone of the North Region and challenges the
      currently available hospital statistics. In this epidemiological context, the
      authors recommend routine laboratory diagnosis of malaria before any treatment,
      especially during the dry season. This is justified both therapeutically and
      economically.

PMID- 21870169
TI  - Adherence and persistence among multiple sclerosis patients after one
      immunomodulatory therapy failure: retrospective claims analysis.
AB  - INTRODUCTION: There are no published data on patient adherence to, and
      persistence with, disease-modifying therapies (DMT) for multiple sclerosis (MS)
      after one immunomodulatory failure. The present study compares secondline DMT
      adherence and persistence among patients with MS. METHODS: Patients with MS
      initiating a second-line treatment with natalizumab, intramuscular interferon
      beta-1a (i.m.-IFNbeta-1a), subcutaneous (s.c.) IFNbeta-1a, interferon beta-1b
      (IFNbeta-1b), and glatiramer acetate (GA) from January 1, 2006 to October 4, 2008
      were identified from a retrospective claims database associated with a large US
      health plan. Adherence was measured with medication possession ratio (MPR);
      adherence indicated MPR >= 0.80. Persistence was measured as time until a minimum
      60-day gap in second-line therapy. Adherence and persistence were modeled with
      logistic and Cox proportional hazard regressions, respectively. RESULTS: The
      study population comprised 1381 patients. Multivariate analysis showed that the
      odds of adherence were significantly higher in the natalizumab cohort compared
      with all other second-line cohorts. The natalizumab cohort was more likely to be
      persistent compared with the i.m.-IFNbeta-1a and IFNbeta-1b cohorts. CONCLUSION:
      The natalizumab cohort was more adherent compared with the other second-line DMT
      cohorts, likely due in large part to active physician involvement and monitoring.
      Adherence to DMT, even after first-line failure, is critical to achieving optimal
      therapeutic benefit.

PMID- 21870171
TI  - Variable clinical presentation and outcome in pediatric patients with resistance
      to thyroid hormone (RTH).
AB  - Resistance to thyroid hormone (RTH) is characterized by elevated levels of
      thyroid hormones, normal or slightly increased TSH levels respondent to TRH,
      resistance to thyroid hormone administration, and variable clinical expression.
      To describe the diverse clinical and biochemical findings of six children from
      five unrelated families with molecular diagnosis of RTH (0.5-12.7 years) and
      their follow-up (3-20 years). All RTH patients and 4 affected parents' harbored
      mutations in exons 9 or 10 of the thyroid receptor beta gene: p.M313T (de novo),
      pN331D, p.L341P, p.L346F, and p.P453L. At consultation 5/6 had goiter, 4/6
      tachycardia, and 3/5 learning disabilities. Median hormone levels were: T(4)
      257.4 nmol/l (NR: 77.2-180.2); FreeT(4) 39.9 pmol/(NR:10.3-28.3); T(3) 4.28
      nmol/l (NR:1.23-3.39) TSH 2.8 mUI/l (NR: 0.5-5) always responsive to TRH. TSH
      levels remained detectable after supraphysiologic T(3) administration while SHBG
      levels showed a paradoxical decrease in 4/6. Thyroid antibodies, initially
      present in two subjects, became positive in other two during follow-up. All
      patients grew normally and presented variable symptoms that were treated
      according to need. Two patients developed psychiatric disorders. Only one of the
      four affected parents exhibited clinical signs of RTH (tachycardia and
      depression). Parent's thyroid profile showed similar TSH and T(3) levels but
      lower T(4) and FT(4) than their children. RTH has a distinctive biochemical
      profile with highly variable clinical manifestations and outcomes. Its
      recognition and molecular characterization avoid misleading diagnosis. Treatment
      has to be instituted according to each subject's own clinical requirements.

PMID- 21870170
TI  - Cross-talk and modulation of signaling between somatostatin and growth factor
      receptors.
AB  - The process of homo- and/or heterodimerization of G-protein coupled receptors
      (GPCRs) and receptor tyrosine kinase (RTK) families are crucial for implicating
      the fundamental properties of receptor proteins including receptor expression,
      trafficking, and desensitization as well as signal transduction. The members of
      GPCR and RTK family constitute largest cell surface receptor proteins and
      regulate physiological functions of cells in response to external and internal
      stimuli. Notably, GPCRs and RTKs play major role in regulation of several key
      cellular functions which are associated with several pathological conditions
      including cancer biology, neurodegenerative and cardiovascular diseases. The
      focus of this review is to highlight the recent findings on the possible cross
      talk between somatostatin receptors (members of GPCR family) and growth factor
      receptors like epidermal growth factor receptors (members of RTK family).
      Furthermore, functional consequences of such an interaction in modulation of
      signaling pathways linked to pathological conditions specifically in cancer are
      discussed.

PMID- 21870172
TI  - Role of biological targeted therapies in gastroenteropancreatic neuroendocrine
      tumours.
AB  - Approximately two-thirds of neuroendocrine tumours (NET) occur in the
      gastrointestinal tract and over 60% present with metastases. With greater insight
      into molecular pathways involved in tumour progression, opportunities are
      presented for the use of targeted therapies in NET. Although a wide array of
      targeted agents has been investigated, only a handful has emerged as forerunners
      from recent clinical trials. This literature review focuses on the use of anti
      angiogenic monoclonal antibody bevacizumab, as well as small molecule inhibitors
      sunitinib and everolimus.

PMID- 21870173
TI  - Application of neutral red retention assay to caged clams (Ruditapes decussatus)
      and crabs (Carcinus maenas) in the assessment of dredged material.
AB  - Dredged material management is a key issue for the protection of aquatic
      environments. The in situ approach using caged bioindicator species has been
      chosen lately as a new methodology for the assessment of dredged material. In a
      tier testing approach, neutral red retention (NRR) assay has been applied as a
      screening tool to detect adverse changes in health status associated with
      contamination. Nevertheless, to authors' knowledge, little is known about the
      application and validation of this technique in sediment bioindicator species and
      under field conditions. Caged Ruditapes decussatus and Carcinus maenas were
      exposed during 28 days to potentially contaminated sediments at three sites in
      Algeciras Bay (SW Spain) and one site in Cadiz Bay (SW Spain). Lysosomal membrane
      stability was measured over time in haemolymph samples of exposed clams and crabs
      using the NRR assay. Sediment characterization of the study sites was performed
      in parallel. NRR time did not vary significantly (p > 0.05) over time in
      organisms from Cadiz Bay. Conversely, significant differences (p < 0.05) in NRR
      time were found in clams and crabs exposed to sediments from Algeciras Bay, which
      exhibited a 30-70% decrease in haemocyte lysosome membrane stability compared to
      day 0. Statistical analysis showed a strong correlation between the drop of
      haemocyte lysosome membrane stability, in both crabs and clams, and the presence
      of metals (p < 0.05) and PAHs (p < 0.01) in the studied sediments. The results
      obtained confirmed the use of NRR assay as a suitable and sensitive method to be
      used in the assessment of sediment quality using as bioindicator species the clam
      R. philippinarum and the crab C. maenas.

PMID- 21870174
TI  - A diet high in fatty fish, bilberries and wholegrain products improves markers of
      endothelial function and inflammation in individuals with impaired glucose
      metabolism in a randomised controlled trial: the Sysdimet study.
AB  - AIMS/HYPOTHESIS: Low-grade inflammation and endothelial dysfunction may play a
      role in the pathogenesis of type 2 diabetes and cardiovascular disease. We
      evaluated whether a diet high in fatty fish, bilberries and wholegrain products
      (Healthy Diet) improves biomarkers reflecting inflammation and endothelial
      dysfunction in individuals with impaired glucose metabolism. METHODS: We
      recruited individuals with impaired glucose metabolism and features of the
      metabolic syndrome into a 12 week, parallel design, dietary intervention trial
      conducted at the Department of Clinical Nutrition, University of Eastern Finland
      (Kuopio, Finland). Randomisation was performed by matching according to sex and
      medians of age, BMI and fasting plasma glucose of the study population at
      screening. The primary endpoint in the present study was the change in plasma
      inflammatory markers and the measurements were performed blinded to group
      assignment. High-sensitivity (hs) C-reactive protein (CRP) and E-selectin
      responses were also analysed separately in participants not using statins (n =
      76). RESULTS: Altogether, 131 individuals were assigned to either the Healthy
      Diet (n = 44), a whole-grain-enriched diet (WGED) (n = 42) or a control (n = 45)
      diet, and 104 participants (mean +/- SD: age 59 +/- 7 years; BMI 31.1 +/- 3.5
      kg/m(2)) who had completed the study, were analysed (Healthy Diet n = 36, WGED n
      = 34 and control diet n = 34). Plasma E-selectin decreased only in the Healthy
      Diet group. This occurred in all group participants (p < 0.05) and also after
      excluding participants using statins (p < 0.05). Plasma hsCRP levels decreased in
      the Healthy Diet (median -17%, p < 0.05) and WGED (median -27%, p < 0.01) groups
      in participants not using statins. Controlling for confounding factors, including
      BMI or insulin sensitivity, did not alter the results. A greater increase in
      plasma concentration of very-long-chain n-3 fatty acids and in the intake of
      fibre during the study was associated with a greater decrease in plasma E
      selectin (p < 0.05). The intake of test breads consumed during the Healthy Diet
      and WGED interventions was inversely associated with the change in hsCRP levels
      (p < 0.001). CONCLUSIONS/INTERPRETATION: Our results suggest that the combined
      effect of fatty fish, bilberries and wholegrain products may improve endothelial
      dysfunction and inflammation in overweight and obese individuals at high risk of
      developing diabetes.

PMID- 21870175
TI  - Abdominal wall component release is a sensible choice for patients requiring
      complicated closure of abdominal defects.
AB  - BACKGROUND: Abdominal wall component release (AWCR) is an operation that
      frequently restores the abdominal wall integrity in both sick and anatomically
      complex patients. The patients reported herein are different from the widely
      reported but somewhat less complex trauma patient, such as following damage
      control laparotomy. AWCR has acceptable postoperative outcomes in terms of
      infection, hernia, and fistula rates. METHODS: We describe the application of
      AWCR in 63 consecutive patients, in whom only 11 (17%) had complementary
      prosthesis use. Unlike many previous reports of AWCR in trauma patients, 47 (75%)
      of these patients had permanent stomas. These patients had undergone a total of
      103 prior abdominal operations (mean 1.7 operations, range 0-7); 29 patients had
      cancer (46%), 11 of which were recurrent, and 16 patients (22%) had serious
      complications of prior surgery. Interestingly, 20 patients (32%) had both prior
      abdominal operations and underlying cancer. RESULTS: In a median follow-up of 32
      months (range 16-120 months), only 15 patients (5 of whom had a stoma) developed
      recurrent abdominal wall hernias with 5 of those being peristomal. No correlation
      was found between prior abdominal operations, intestinal stomas, and
      contamination source at time of surgery with recurrence of hernia (p > 0.05). The
      41 patients (86%) with an intact abdominal wall (free of recurrent hernia) had a
      median follow-up of 27 months (range 13-117 months). Twelve patients (19%) had a
      source of abdominal/abdominal wall contamination present at the time of AWCR.
      Only 1 of the 11 patients in whom complementary prosthesis was used developed
      infection. Other infectious complications were noted in 12 patients (19%),
      including fistula in 1 patient who required reoperation. CONCLUSIONS: AWCR offers
      acceptable results in very high-risk patients with tolerable postoperative
      infection rates.

PMID- 21870177
TI  - Neuropsychological profile of Italian children and adolescents with 22q11.2
      deletion syndrome with and without intellectual disability.
AB  - As individuals with chromosome 22q11.2 deletion syndrome (22q11DS) show a wide
      range of IQs, intellectual heterogeneity could mask the neuropsychological
      profile of the syndrome. This study was designed to identify specific
      neuropsychological features of children and adolescents with 22q11DS by taking
      into account the possible source of variability deriving from intellectual
      disability (ID). First, we compared several neuropsychological domains involving
      linguistic, visual-motor/visual-perceptual and memory abilities in 34 children
      and adolescents with 22q11DS and 83 mental age-matched typically developing (TD)
      participants. Then, we selected participants with 22q11DS according to whether or
      not they had ID and compared their neuropsychological profiles with those of
      chronological age-matched TD controls. Although language and several aspects of
      memory have been found impaired only in children with 22q11DS with ID, deficits
      in visual-spatial abilities and visual-object short-term memory persist in
      participants without ID and might be considered a characteristic of 22q11DS, not
      just related to the presence of ID. On the basis of our findings, children and
      adolescents with 22q11DS cannot be considered as a single group with a
      homogeneous neuropsychological profile and must be studied in relation to their
      global intellectual abilities.

PMID- 21870179
TI  - Balancing equity and efficiency in the Dutch basic benefits package using the
      principle of proportional shortfall.
AB  - Economic evaluations are increasingly used to inform decisions regarding the
      allocation of scarce health care resources. To systematically incorporate
      societal preferences into these evaluations, quality-adjusted life year gains
      could be weighted according to some equity principle, the most suitable of which
      is a matter of frequent debate. While many countries still struggle with equity
      concerns for priority setting in health care, the Netherlands has reached a broad
      consensus to use the concept of proportional shortfall. Our study evaluates the
      concept and its support in the Dutch health care context. We discuss arguments in
      the Netherlands for using proportional shortfall and difficulties in
      transitioning from principle to practice. In doing so, we address universal
      issues leading to a systematic consideration of equity concerns for priority
      setting in health care. The article thus has relevance to all countries
      struggling with the formalization of equity concerns for priority setting.

PMID- 21870180
TI  - A living life, a living death: Bessie Head's writing as a survival strategy.
AB  - This paper explores Bessie Head's writing as a survival strategy through which
      she transformed her lived experience into imaginative literature, giving meaning
      and purpose to a life under permanent threat from the dominant group first in
      South Africa and later in Botswana. This threat included the destructive effect
      of the many fixed labels imposed upon her including: a 'Coloured' woman, the
      daughter of a woman designated mad, an exile, a psychotic, a tragic black woman,
      and a Third World woman writer. Her endeavours to avoid and defeat such limited,
      static definitions produced work characterised by contradiction and paradox,
      through which she asserted her right to survive and determined, like Makhaya in
      When Rain Clouds Gather, to establish 'a living life' in place of the 'living
      death that a man could be born into' (Head 1989, 136). Through a combination of
      Head's personal letters and papers and her published work, it can be seen how her
      particular preoccupations and experiences including her life in exile, her
      beliefs about her origins, her relationship to her absent mother, her distress,
      her madness and her need for love and for work were transformed into writing
      which expresses not only the destructive circumstances of her life but also its
      life-affirming aspects. Her writing was also a means by which she could create
      identities to express the dangers she encountered from the all-pervasive power
      structures which influenced her life and her sense of self, as well as ways to
      transcend them, enabling her to say in the last years of her life 'I am no
      failure' (20.2.1986 KMM BHP).

PMID- 21870178
TI  - Telomere length and mental well-being in elderly men from the Netherlands and
      Greece.
AB  - Telomeres, repetitive DNA sequences that promote chromosomal stability, have been
      related to different measures of mental well-being and self-rated health, but
      mainly in women during adulthood. We aimed to investigate whether accelerated
      telomere shortening is associated with poor mental well-being and poor self-rated
      health in community-dwelling elderly men. Leukocyte telomere length was measured
      using quantitative PCR in two different samples of 203 elderly men (mean age 78
      years) from the Netherlands in 1993, and 123 elderly men (mean age 84 years) from
      Greece in 2000. We also obtained follow-up data in 2000 from 144 Dutch subjects,
      of whom 75 had paired telomere length data in 1993 and 2000. Mental well-being
      was conceptualized as dispositional optimism, depressive symptoms, cognitive
      functioning, and loneliness. Linear regression analyses were used to study the
      association between telomere length, measures of mental well being, and self
      rated health, while adjusting for potential confounders. In cross-sectional
      analyses, leukocyte telomere length was not associated with measures of mental
      well-being and self-rated health, neither in the Netherlands nor in Greece. Also,
      the rate of leukocyte telomere shortening (mean decrease: 0.28 kbp over 7 years)
      in the 75 Dutch participants with longitudinal data was not associated with
      changes in different measures of mental well-being and self-rated health. Thus,
      our results provide no support for a relationship between leukocyte telomere
      length and mental well-being in elderly community-dwelling men.

PMID- 21870176
TI  - Metabolic surgery-principles and current concepts.
AB  - INTRODUCTION: In the almost six decades of bariatric surgery, a variety of
      surgical approaches to treating morbid obesity have been developed. HISTORY AND
      EVOLUTION: Rather than prior techniques being continually superseded by new ones,
      a broad choice of surgical solutions based on restrictive, malabsorptive, humoral
      effects, or combinations thereof, is now available. In fact, in recent years, the
      advent of surgically modifying human metabolism promises new approaches to
      ameliorate traditionally medically treated metabolic entities, i.e., diabetes,
      even in the non-obese. The understanding of the various metabolic effects have
      led to a paradigm shift from bariatric surgery as a solely weight-reducing
      procedure to metabolic surgery affecting whole body metabolism. CONCLUSION: The
      bariatric surgeon now faces the challenge and opportunity of selecting the most
      suitable technique for each individual case. To assist in such decision-making,
      this review, Metabolic surgery-principles and current concepts, is presented,
      tracing the historical development; describing the various surgical techniques;
      elucidating the mechanisms by which glycemic control can be achieved that involve
      favorable changes in insulin secretion and insulin sensitivity, gut hormones,
      adipokines, energy expenditure, appetite, and preference for low glycemic index
      foods; as well as exploring the fascinating future potential of this new
      interdisciplinary field.

PMID- 21870181
TI  - Chess & schizophrenia: Murphy v Mr Endon, Beckett v Bion.
AB  - This paper reconvenes Samuel Beckett's psychotherapy with Wilfred Bion during
      1934-1936 during which time Beckett's conceived and began writing this second
      novel, Murphy. Based on Beckett's visits to the Bethlem & Maudsley Hospital and
      his observation of the male nurses, the climax of Murphy is a chess match between
      Mr Endon (a male schizophrenic patient) and Murphy (a male psychiatric nurse).
      The precise notation of the Endon v Murphy chess match tells us that the Beckett
      intended it to be an exemplar of an anti-match, perhaps a metaphor for the
      tragedy of being locked into madness. It is also argued that the match offers us
      insight into Beckett's experience of the process of psychotherapy with Bion.
      Based on new information from Beckett's nephew and Bion's widow, hypotheses about
      the long term impact of the Bion-Beckett analysis are advanced as a mutual
      experience which shaped the lives and later literary output of both men,
      producing conjoined career writings which continue to offer us stark and sublime
      condensations of depression, psychosis, and the challenges of therapy and
      recovery.

PMID- 21870183
TI  - Deconstructing a path to reconstructing reproductive organs.

PMID- 21870182
TI  - Prediction of oocyte developmental competence in ovine using glucose-6-phosphate
      dehydrogenase (G6PDH) activity determined at retrieval time.
AB  - PURPOSE: To determine whether G6PDH-activity measured by Brilliant Cresyl Blue
      known as BCB dye, predicts developmental competence within cohorts of ovine
      oocytes. METHODS: Ovine oocytes were exposed to BCB staining and categorized into
      two groups: BCB+ (blue cytoplasm, low G6PDH-activity) and BCB- (colorless
      cytoplasm, high G6PDH-activity). After maturation in vitro, oocytes were
      subjected to fertilization followed by in vitro embryo culture. RESULTS: We
      observed a significant difference in oocyte diameter considering BCB+ and BCB-
      oocytes. BCB+ and Control groups showed significantly higher maturation rates
      compared to BCB- group. There were significantly more cleaved embryos in BCB+ and
      control groups than in BCB- group. Blastocyst rate was significantly higher for
      BCB+ group compared to control and BCB- groups with control group being
      significantly higher than BCB- group. CONCLUSION: G6PDH-activity is a strong
      predictive marker of oocyte competence and may be useful in identifying oocytes
      with a good prognosis for further develop.

PMID- 21870184
TI  - A feeding frenzy for embryos and stem cells: meeting the media frontally!

PMID- 21870185
TI  - Association study of HLA-B alleles with idiopathic male infertility in Han
      population of China.
AB  - PURPOSE: To investigate the distributions of HLA-B alleles and estimate their
      associations with idiopathic male infertility in Chinese Han population. METHODS:
      Polymerase chain reaction-sequence-based typing (PCR-SBT) method was used for DNA
      typing at HLA-B locus in 109 patients with idiopathic male infertility and 152
      healthy controls in male Han population of Shaanxi Province, situated in
      northwestern China. RESULTS: In total, we detected 45 HLA-B alleles in idiopathic
      infertile patients, 48 HLA-B alleles in control subjects. However, no significant
      differences of these allelic frequencies were found between the infertile
      patients and the controls. CONCLUSION: HLA-B gene was unlikely a major risk
      factor of idiopathic male infertility in this sample population. As different
      populations have different HLA polymorphisms, investigation of the relationship
      of other HLA genes and idiopathic male infertility with larger sample size, is
      warranted in the future.

PMID- 21870187
TI  - The effect of maternal stress on birth outcomes: exploiting a natural experiment.
AB  - A growing body of research highlights that in utero conditions are consequential
      for individual outcomes throughout the life cycle, but research assessing causal
      processes is scarce. This article examines the effect of one such condition
      prenatal maternal stress-on birth weight, an early outcome shown to affect
      cognitive, educational, and socioeconomic attainment later in life. Exploiting a
      major earthquake as a source of acute stress and using a difference-in-difference
      methodology, I find that maternal exposure to stress results in a significant
      decline in birth weight and an increase in the proportion of low birth weight.
      This effect is focused on the first trimester of gestation, and it is mediated by
      reduced gestational age rather than by factors affecting the intrauterine growth
      of term infants. The findings highlight the relevance of understanding the early
      emergence of unequal outcomes and of investing in maternal well-being since the
      onset of pregnancy.

PMID- 21870186
TI  - CYP1A1, GSTM1 and GSTT1 polymorphisms, tobacco and alcohol status and risk of
      head and neck squamous cell carcinoma.
AB  - We examined the influence of the CYP1A1 A4889G and T6235C, GSTM1 and GSTT1
      polymorphisms, involved in carcinogen metabolism, on the head and neck (HN)
      squamous cell carcinoma (SCC) risk. DNA from 142 HNSCC patients and 142 controls
      was analysed by polymerase chain reaction (PCR)-restriction fragment length
      polymorphism or multiplex-PCR for the polymorphisms analyses. Excesses of the
      CYP1A1 4889AG+GG and 4889AG+GG plus GSTT1 null genotype were seen in patients
      with heavy tobacco habit compared with controls (41.9% versus 26.8%, P = 0.03;
      26.2% versus 10.3%, P = 0.04, respectively). Carriers of the referred genotypes
      and heavy tobacco consumption were under a 2.0-fold and 2.8-fold increased risks
      for HNSCC than others, respectively. The CYP1A1 6235TC+CC plus GSTM1 and GSTT1
      null genotypes were more common in pharyngeal SCC patients than in controls (5.3%
      versus 0.7%, P = 0.04). Carriers of the combined genotype had 16.0-fold increased
      risk for the disease than others. The frequency of one null genotype of the GSTM1
      or GSTT1 gene was higher in patients with pharyngeal SCC and heavy smoking status
      than in controls (76.3% versus 57.7%, P = 0.04). Carriers of the referred
      genotype and heavy tobacco status had a 2.4-fold increased risk for pharyngeal
      SCC than others. In contrast, the CYP1A1 6235TC+CC genotype was more common in
      controls than in laryngeal SCC patients (35.9% versus 21.6%, P = 0.01). Carriers
      of the genotype had a 0.2-fold decreased risk for the disease than others. Our
      data present preliminary evidence that inherited combined CYP1A1 A4889G and
      T6235C abnormalities and GSTM1 and GSTT1 pathways are important determinants of
      HNSCC, particularly pharyngeal SCC in heavy smoking individuals from south
      eastern Brazil.

PMID- 21870188
TI  - The effects of rapid desiccation on estimates of plant genome size.
AB  - Flow cytometry has become the dominant method for estimating nuclear DNA content
      in plants, either for ploidy determination or quantification of absolute genome
      size. Current best practices for flow cytometry involve the analysis of fresh
      tissue, however, this imposes significant limitations on the geographic scope and
      taxonomic diversity of plants that can be included in large-scale genome size
      studies. Dried tissue has been used increasingly in recent years, but largely in
      the context of ploidy analysis. Here we test rapid tissue drying with silica gel
      as a method for use in genome size studies, potentially enabling broader
      geographic sampling of plants when fresh tissue collection is not feasible. Our
      results indicate that rapid drying introduces comparatively minor error (<10%),
      which is similar to the error introduced by other common methodological
      variations such as instrument. Additionally, the relative effect of drying on
      genome size and data quality varied between species and buffers. Tissue
      desiccation provides a promising approach for expanding our knowledge of plant
      genome size diversity.

PMID- 21870189
TI  - A novel and mild isolation procedure of chlorosomes from the green sulfur
      bacterium Chlorobaculum tepidum.
AB  - In this article, we developed a new and mild procedure for the isolation of
      chlorosomes from a green sulfur bacterium Chlorobaculum tepidum. In this
      procedure, Fenna-Matthews-Olson (FMO) protein was released by long cold treatment
      (6 degrees C) of cells under the presence of a chaotrope (2 M NaSCN) and 0.6 M
      sucrose. Chlorosomes were released by an osmotic shock of the cold-treated cells
      after the formation of spheroplasts without mechanical disruption. Chlorosomes
      were finally purified by a sucrose step-wise density gradient centrifugation. We
      obtained two samples with different density (20 and 23% sucrose band,
      respectively) and compared them by SDS-PAGE, absorption spectroscopy at 80 K,
      fluorescence and CD spectroscopy at room temperature. Cells whose absorption
      maximum was longer than 750 nm yielded higher amount of the 20% sucrose fraction
      than those having an absorption maximum shorter than 750 nm.

PMID- 21870190
TI  - Measuring outcomes in Parkinson's disease: a multi-perspective concept mapping
      study.
AB  - PURPOSE: To identify and develop a conceptual map of prioritized areas and to
      determine their relative importance for outcome measurement in clinical
      Parkinson's disease (PD) trials, from the perspectives of health care
      professionals and people with PD. METHOD: We used concept mapping, a
      qualitative/quantitative method consisting of three steps: item generation
      through focus groups (n = 27; 12 people with PD, 12 health care professionals, 3
      researchers), item sorting and rating (n = 38; 19 people with PD, 19 health care
      professionals), and data analysis (multidimensional scaling, cluster analysis).
      RESULTS: Ninety-nine items and eight clusters were generated. Clusters
      representing Participation; Mobility and motor functioning; Cognitive and
      executive functioning; and Emotions were the most homogenous. Statements within
      clusters representing Energy and abilities; Autonomic dysfunctions; Sensory,
      speech and swallowing problems; and Neuropsychiatric symptoms also related to
      statements outside their respective clusters. Clusters rated most important were
      Participation and Mobility and motor functioning, and the highest rated items
      were quality of life, walking ability, and sleeping problems. CONCLUSION: By the
      use of concept mapping, a multi-perspective conceptual map of prioritized aspects
      for the outcome measurement in PD was defined. These findings provide an initial
      conceptual basis toward improved outcome measurement priorities in clinical PD
      trials.

PMID- 21870191
TI  - The inductive effects of Centella asiatica on rat spermatogenic cell apoptosis in
      vivo.
AB  - Centella asiatica (L.) Urban has been traditionally used for the treatment of
      various disease and as a food for thousands of years in various parts of the
      world including eastern Asia, China and India. The goal of this study was to
      investigate the effects of Centella asiatica aqueous leaf extract on the
      induction of spermatogenic cell apoptosis in male rats. After lethal dose
      (LD(50)) assessment of plant extract, rats were divided in five groups. The
      experimental groups received orally 10, 50, 80 and 100 mg/kg aqueous leaf extract
      daily for 60 days and the control group received just water. After 60 days, body
      and testis weight were measured and blood samples were taken from the heart. To
      evaluate apoptosis and histological changes, tissue samples obtained from rat
      testes were stained by TUNEL assay and hematoxylin and eosin stain. Results
      showed that the sperm count, motility, and viability and the number of
      spermatogenic cells in the seminiferous tubules were significantly decreased
      compared with the control group. The number of apoptotic germ cells per
      seminiferous tubule cross-section was significantly increased in the experimental
      group (18.11 +/- 3.5) compared with the control group (8.7 +/- 0.81) (P < 0.05).
      Serum testosterone, follicle-stimulating hormone, and luteinizing hormone levels
      also showed significant decreases in the experimental groups (P < 0.05). There
      was also a significant decrease in testis weight in experimental groups compared
      with the control group (P < 0.05). It is concluded that Centella asiatica has
      toxicological effects on the reproductive system in male rats and, therefore, it
      is suggested that leaf extracts of Centella asiatica possess antifertility
      effects in the male rat.

PMID- 21870193
TI  - A selection of recent original research papers.

PMID- 21870192
TI  - Conjoint analysis versus rating and ranking for values elicitation and
      clarification in colorectal cancer screening.
AB  - PURPOSE: To compare two techniques for eliciting and clarifying patient values
      for decision making about colorectal cancer (CRC) screening: choice-based
      conjoint analysis and a rating and ranking task. METHODS: Using our decision lab
      registry and university e-mail lists, we recruited average risk adults ages 48-75
      for a written, mailed survey. Eligible participants were given basic information
      about CRC screening and six attributes of CRC screening tests, then randomized to
      complete either a choice-based conjoint analysis with 16 discrete choice tasks or
      a rating and ranking task. The main outcome was the most important attribute, as
      determined from conjoint analysis or participant ranking. Conjoint analysis-based
      most important attribute was determined from individual patient-level utilities
      generated using multinomial logistic regression and hierarchical Bayesian
      modeling. RESULTS: Of the 114 eligible participants, 104 completed and returned
      questionnaires. Mean age was 57 (range 48-73), 70% were female, 88% were white,
      71% were college graduates, and 62% were up to date with CRC screening. Ability
      to reduce CRC incidence and mortality was the most frequent most important
      attribute for both the conjoint analysis (56% of respondents) and rating/ranking
      (76% of respondents) groups, and these proportions differed significantly between
      groups (absolute difference 20%, 95% CI 3%, 37%, p =0.03). There were no
      significant differences between groups in proportion with clear values (p =
      0.352), intent to be screened (p = 0.226) or unlabelled test preference (p =
      0.521) CONCLUSIONS: Choice-based conjoint analysis produced somewhat different
      patterns of attribute importance than a rating and ranking task, but had little
      effect on other outcomes.

PMID- 21870194
TI  - Metal-metal interactions in linear tri-, penta-, hepta-, and nona-nuclear
      ruthenium string complexes.
AB  - Density functional theory (DFT) methodology was used to examine the structural
      properties of linear metal string complexes: [Ru(3)(dpa)(4)X(2)] (X = Cl(-), CN(
      ), NCS(-), dpa = dipyridylamine(-)), [Ru(5)(tpda)(4)Cl(2)], and hypothetical, not
      yet synthesized complexes [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] (tpda =
      tri-alpha-pyridyldiamine(2-), tpta = tetra-alpha-pyridyltriamine(3-), ppta =
      penta-alpha-pyridyltetraamine(4-)). Our specific focus was on the two longest
      structures and on comparison of the string complexes and unsupported ruthenium
      backboned chain complexes, which have weaker ruthenium-ruthenium interactions.
      The electronic structures were studied with the aid of visualized frontier
      molecular orbitals, and Bader's quantum theory of atoms in molecules (QTAIM) was
      used to study the interactions between ruthenium atoms. The electron density was
      found to be highest and distributed most evenly between the ruthenium atoms in
      the hypothetical [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] string
      complexes.

PMID- 21870195
TI  - Modeling translocation dynamics of strand displacement DNA synthesis by DNA
      polymerase I.
AB  - A model is presented for the translocation dynamics of the strand displacement
      DNA synthesis by DNA polymerases such as polymerase I family. (i) The model gives
      an explanation to the experimental results which showed that the rate of strand
      displacement DNA synthesis is nearly consistent with that of single stranded
      primer extension synthesis, although the two are expected to have substantial
      differences in their energetics. (ii) During strand displacement DNA synthesis,
      the pausing at the specific sequence is considered to be due to an affinity of
      the fingers subdomain for the specific sequence of dsDNA downstream of the single
      strand. The theoretical results on the sequence-dependent pausing dynamics such
      as the mean pausing lifetimes and the distribution of the pausing lifetime are
      consistent with the experimental data. Moreover, predicted results are presented
      for the binding affinity of the fingers subdomain for the specific sequence of
      dsDNA and the dependence of the mean sequence-dependent pausing lifetime on the
      external force acting on the polymerase.

PMID- 21870197
TI  - Theoretical study of BN4: potential precursors of high energy density materials
      (HEDMs).
AB  - Ab initio (MP2) and density functional theory (DFT) methods were used to examine
      nine isomers of the doublet BN(4) species with the 6-311 + G(d) basis set. To our
      knowledge, these nine structures are all first reported here. Energy analysis
      indicates that the C(2v) branched structure is the global minimum of potential
      energy surface. Research results show that the C(2v) branched, the cis-linear,
      the C(4v) pyramidal, and the C(S) five-membered ring structures are likely to be
      stable and to be observed experimentally. Among these four kinetically stable
      species, the last three are suitable to be used as potential precursors of HEDMs
      due to their high dissociation energies. However, the C(2v) bent, the trans
      linear, the D(2) bicyclic, the C(2v) four-membered ring, and the C(2v) cage
      structures are kinetically unstable due to their low dissociation or
      isomerization barriers. Two synthesis pathways of the C(2v) branched isomer were
      located. It seems more feasible to synthesize this species by linear NBN and
      N(2).

PMID- 21870196
TI  - Computational studies on full-length Ku70 with DNA duplexes: base interactions
      and a helical path.
AB  - The Ku70/80 heterodimer is among the first responding proteins to recognize and
      bind the DNA double strand breaks (DSBs). Once Ku is loaded at the DSB, it works
      as a scaffold to recruit other repair factors in non-homologous end joining
      thereby facilitates the following repair processes. In this work, we
      characterized the detailed interactions and binding free energies between a Ku70
      subunit and several DNA duplexes, by using some well-established computational
      methods. The results reveal that the structure of the protein may suffer certain
      contractions without the company of Ku80, and may experience large conformational
      changes in the presence of different DNA duplexes. Notably, we observe the
      closest interactions between Ku70 and DNA can be easily strengthened to form H
      bonds with the bases in the minor groove, which is unexpected. However, this
      finding is supported by the presence of a similar bond between Ku80 and DNA in
      the published crystal structure (PDB code 1JEY). We suggest that these
      interactions are responsible for the observed pausing sites when Ku translocates
      along DNA and the subtle difference in binding with AT- and GC-rich DNA ends.
      Additionally, simulations indicate the inner surface of the ring encircling the
      DNA is not flat, but contains a delicate clamp like structure, which is ideal to
      grip the two strands of DNA in the minor groove and confine the movement of the
      duplex in a unique helical path.

PMID- 21870198
TI  - Structure-based functional inference of hypothetical proteins from Mycoplasma
      hyopneumoniae.
AB  - Enzootic pneumonia caused by Mycoplasma hyopneumoniae is a major constraint to
      efficient pork production throughout the world. This pathogen has a small genome
      with 716 coding sequences, of which 418 are homologous to proteins with known
      functions. However, almost 42% of the 716 coding sequences are annotated as
      hypothetical proteins. Alternative methodologies such as threading and
      comparative modeling can be used to predict structures and functions of such
      hypothetical proteins. Often, these alternative methods can answer questions
      about the properties of a model system faster than experiments. In this study, we
      predicted the structures of seven proteins annotated as hypothetical in M.
      hyopneumoniae, using the structure-based approaches mentioned above. Three
      proteins were predicted to be involved in metabolic processes, two proteins in
      transcription and two proteins where no function could be assigned. However, the
      modeled structures of the last two proteins suggested experimental designs to
      identify their functions. Our findings are important in diminishing the gap
      between the lack of annotation of important metabolic pathways and the great
      number of hypothetical proteins in the M. hyopneumoniae genome.

PMID- 21870199
TI  - Characterization of molecular recognition of phosphoinositide-3-kinase alpha
      inhibitor through molecular dynamics simulation.
AB  - Phosphatidylinositol 3-kinase alpha (PI3Kalpha) is a promising target for
      anticancer drug discovery due to its overactivation in tumor cells. To
      systematically investigate the interactions between PI3Kalpha and PIK75 which is
      the most selective PI3Kalpha inhibitor reported to date, molecular docking,
      molecular dynamics simulation, and ensuing energetic analysis were utilized. The
      binding free energy between PI3Kalpha and PIK75 is -10.04 kcal*mol(-1) using
      MMPBSA method, while -13.88 kcal*mol(-1) using MMGBSA method, which is beneficial
      for the binding. The van der Waals/hydrophobic and electrostatic interactions
      play critical roles for the binding. The binding mode of PIK75 for PI3Kalpha is
      predicted. The conserved hydrophobic adenine region of PI3Kalpha made up of
      Ile800, Ile848, Val850, Val851, Met922, Phe930, and Ile932 accommodates the flat
      6-bromine imidazo[1,2-a]pyridine ring of PIK75. The 2-methyl-5-nitrophenyl group
      of PIK75 extends to the P-loop region, and has four hydrogen-bond arms with the
      backbone and side chain of Ser773 and Ser774. And the distinct conformation of
      the P-loop induced by PIK75 is speculated to be responsible for the selectivity
      profile of PIK75. The predicted binding mode of PIK75 for PI3Kalpha presented in
      this study may help design high affinity and selective compounds to target
      PI3Kalpha.

PMID- 21870200
TI  - Temporal profile of gene transcription noise modulated by cross-talking signal
      transduction pathways.
AB  - Gene transcription is a central cellular process and is stochastic in nature. The
      stochasticity has been studied in real cells and in theory, but often for the
      transcription activated by a single signaling pathway at steady-state. As
      transcription of many genes is involved with multiple pathways, we investigate
      how the transcription efficiency and noise is modulated by cross-talking
      pathways. We model gene transcription as a renewal process for which the gene can
      be turned on by different pathways. We determine the transcription efficiency by
      solving a system of differential equations, and obtain the mathematical formula
      of the noise strength by the Laplace transform and standard techniques in renewal
      theory. Our numerical examples demonstrate that cross-talking pathways are
      capable of inducing more cells to transcribe than the steady-state level after a
      short time period of signal transduction, and creating exceedingly high
      stationary transcription noise strength. In contrast, it is shown that one
      signaling pathway alone is unable to do so. Very strikingly, it is observed that
      the noise strength varies gradually over most values of the system parameters,
      but changes abruptly over a narrow range in the neighborhoods of some critical
      parameter values.

PMID- 21870201
TI  - Assessing coverage of protein interaction data using capture-recapture models.
AB  - Protein interaction networks comprise thousands of individual binary links
      between distinct proteins. Whilst these data have attracted considerable
      attention and been the focus of many different studies, the networks, their
      structure, function, and how they change over time are still not fully known.
      More importantly, there is still considerable uncertainty regarding their size,
      and the quality of the available data continues to be questioned. Here, we employ
      statistical models of the experimental sampling process, in particular capture
      recapture methods, in order to assess the false discovery rate and size of
      protein interaction networks. We uses these methods to gauge the ability of
      different experimental systems to find the true binary interactome. Our model
      allows us to obtain estimates for the size and false-discovery rate from simple
      considerations regarding the number of repeatedly interactions, and provides
      suggestions as to how we can exploit this information in order to reduce the
      effects of noise in such data. In particular our approach does not require a
      reference dataset. We estimate that approximately more than half of the true
      physical interactome has now been sampled in yeast.

PMID- 21870202
TI  - Fifty years of changes in UV Index and implications for skin cancer in Australia.
AB  - Surface ultraviolet (UV) radiation plays an important role in human health.
      Increased exposure to UV radiation increases the risk of skin cancer. In
      Australia, public campaigns to prevent skin cancer include the promotion of daily
      UV forecasts. If all other atmospheric factors are equal, stratospheric ozone
      decreases result in UV increases. Given that Australia still has the highest skin
      cancer rates in the world, it is important to monitor Australia's stratospheric
      ozone and UV radiation levels over time because of the effects cumulative
      exposure can have on humans. In this paper, two long-term ozone datasets derived
      from surface and satellite measurements, a radiation code and atmospheric
      meteorological fields are used to calculate clear-sky UV radiation over a 50-year
      period (1959-2009) for Australia. The deviations from 1970-1980 levels show that
      clear-sky UV is on the rise. After the 1990s, an overall annual increase from 2
      to 6% above the 1970-1980 levels was observed at all latitudes. Examining the
      summer and winter deviations from 1970-1980 showed that the winter signal
      dominated the annual changes, with winter increases almost twice those in summer.
      With ozone levels not expected to recover to pre-depletion levels until the
      middle of this century, UV levels are expected to continue to rise. Combined with
      Australians favoring an outdoor life-style, when temperatures are warmer, under
      high levels of UV, the associated risk of skin cancer will increase.

PMID- 21870203
TI  - Pharmacodynamic model of sodium-glucose transporter 2 (SGLT2) inhibition:
      implications for quantitative translational pharmacology.
AB  - Sodium-glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of
      agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of
      SGLT2 leads to improved glycemic control through increased urinary glucose
      excretion (UGE). In this study, a biologically based
      pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was
      developed. The derived model was used to characterize the acute PK/PD
      relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative
      translational pharmacology of dapagliflozin was examined through both prospective
      simulation and direct modeling of mean literature data obtained for dapagliflozin
      in healthy subjects. Prospective simulations provided time courses of UGE that
      were of consistent shape to clinical observations, but were modestly biased
      toward under prediction. Direct modeling provided an improved characterization of
      the data and precise parameter estimates which were reasonably consistent with
      those predicted from preclinical data. Overall, these results indicate that the
      acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be
      reasonably well predicted from preclinical data through rational accounting of
      species differences in pharmacokinetics, physiology, and SGLT2 pharmacology.
      Because these data can be generated at the earliest stages of drug discovery, the
      proposed model is useful in the design and development of novel SGLT2 inhibitors.
      In addition, this model is expected to serve as a useful foundation for future
      efforts to understand and predict the effects of SGLT2 inhibition under chronic
      administration and in other patient populations.

PMID- 21870204
TI  - Comparative spatiotemporal analysis of root aerenchyma formation processes in
      maize due to sulphate, nitrate or phosphate deprivation.
AB  - Nitrate (N), phosphate (P) or sulphate (S) deprivation causes aerenchyma
      formation in maize (Zea mays L.) nodal roots. The exact mechanisms that trigger
      the formation of aerenchyma under these circumstances are unclear. We have
      compared aerenchyma distribution across the nodal roots of first whorl (just
      emerging in 10-day-old seedlings), which were subject to S, N or P deprivation
      over a period of 10 days in connection with oxygen consumption, ATP
      concentration, cellulase and polygalacturonase activity in the whole root. The
      effect of deprivation on aerenchyma formation was examined using light and
      electron microscopy, along with in situ detection of calcium and of reactive
      oxygen species (ROS) by fluorescence microscopy. Aerenchyma was not found in the
      root base regardless of the deprivation. Programmed cell death (PCD) was observed
      near the root tip, either within the first two days (-N) or a few days later (-S,
      -P) of the treatment. Roots at day 6 under all three nutrient-deprived conditions
      showed signs of PCD 1 cm behind the cap, whereas only N-deprived root cells 0.5
      cm behind the cap showed severe ultrastructural alterations, due to advanced PCD.
      The lower ATP concentration and the higher oxygen consumptions observed at day 2
      in N-, P- and S-deprived roots compared to the control indicated that PCD may be
      triggered by perturbations in energy status of the root. The peaks of cellulase
      activity located between days 3 (-N) and 6 (-P), along with the respective
      alterations in polygalacturonase activity, indicated a coordination which
      preceded aerenchyma formation. ROS and calcium seemed to contribute to PCD
      initiation, with ROS possessing dual roles as signals and eliminators. All the
      examined parameters presented both common features and characteristic variations
      among the deprivations.

PMID- 21870205
TI  - Seeing while acting: hand movements can modulate attentional capture by motion
      onset.
AB  - The onset of new motion has been shown to be a very robust cause of attentional
      capture, generating a processing advantage for the location of motion onset
      regardless of the observer's concurrent goal. The present study, motivated by the
      common-coding account of action and perception, examined whether the effect of
      motion onset on visual attention can be modulated by the observer's mode of
      action. Specifically, the common-coding account predicts that preparing an action
      can render the features that are used in the action plan less available for
      visual processes. Consistent with this hypothesis, in Experiment 1 the magnitude
      of attentional capture caused by a single motion onset was reduced when this
      motion was similar to the observer's response (i.e., along the same axis).
      Similarly, in Experiment 2 the onset of a response-different motion gained a
      processing advantage over the response-similar motion onset when the two were
      presented simultaneously. Since both types of motion were present in every trial,
      the results of Experiment 2 suggest that response similarity affected visual
      attentional processes rather than motor processes. Together, these results
      suggest that the processes of attentional prioritization caused by motion onset
      can be modulated by the observer's concurrent action.

PMID- 21870206
TI  - Discrimination thresholds for haptic perception of volume, surface area, and
      weight.
AB  - The present study investigated the human ability to discriminate the size of 3-D
      objects by touch. Experiment 1 measured the just noticeable differences (JNDs)
      for three tasks: (1) discrimination of volume without availability of weight
      information, (2) discrimination of volume with weight information available, and
      (3) discrimination of surface area. Stimuli consisted of spheres, cubes, and
      tetrahedrons. For all shapes, two reference sizes were used (3.5 and 12 cm(3)).
      No significant effect of task on the discriminability of objects was found, but
      the effects of shape and size were significant, as well as the interaction
      between these two factors. Post hoc analysis revealed that for the small
      reference, the Weber fractions for the tetrahedron were significantly larger than
      the fractions for the cube and the sphere. In Experiment 2, the JNDs for haptic
      perception of weight were measured for the same objects as those used in
      Experiment 1. The shape of objects had no significant effect on the Weber
      fractions for weight, but the Weber fractions for the small stimuli were larger
      than the fractions for the large stimuli. Surprisingly, a comparison between the
      two experiments showed that the Weber fractions for weight were significantly
      larger than the fractions for volume with availability of weight information.
      Taken together, the results reveal that volume and weight information are not
      effectively combined in discrimination tasks. This study provides detailed
      insight into the accuracy of the haptic system in discriminating objects' size.
      This substantial set of data satisfies the need for more fundamental knowledge on
      haptic size perception, necessary for a greater understanding of the perception
      of related properties, as well as of more general perceptual processes.

PMID- 21870207
TI  - Urinary tract effects after multifocal nonthermal irreversible electroporation of
      the kidney: acute and chronic monitoring by magnetic resonance imaging,
      intravenous urography and urinary cytology.
AB  - PURPOSE: The nonthermal irreversible electroporation (NTIRE) is a novel potential
      ablation modality for renal masses. The aim of this study was the first
      evaluation of NTIRE's effects on the renal urine-collecting system using
      intravenous urography (IVU) and urinary cytology in addition to histology and
      magnetic resonance imaging (MRI). METHODS: Eight percutaneous NTIRE ablations of
      the renal parenchyma, including the calyxes or pelvis, were performed in three
      male swine. MRI, IVU, histology, and urinary cytology follow-ups were performed
      within the first 28 days after treatment. RESULTS: MRI and histological analysis
      demonstrated a localized necrosis 7 days and a localized scarification of the
      renal parenchyma with complete destruction 28 days after NTIRE. The urine
      collecting system was preserved and showed urothelial regeneration. IVU and MRI
      showed an unaltered normal morphology of the renal calyxes, pelvis, and ureter. A
      new urinary cytology phenomenon featured a temporary degeneration by individual
      vacuolization of detached transitional epithelium cells within the first 3 days
      after NTIRE. CONCLUSIONS: This first urographical, urine-cytological, and MRI
      evaluation after porcine kidney NTIRE shows multifocal parenchyma destruction
      while protecting the involved urine-collecting system with regenerated urothelial
      tissue. NTIRE could be used as a targeted ablation method of centrally located
      renal masses.

PMID- 21870208
TI  - Quantitative discomanometry: correlation of intradiscal pressure values to pain
      reduction in patients with intervertebral disc herniation treated with
      percutaneous, minimally invasive, image-guided techniques.
AB  - PURPOSE: To illustrate quantitative discomanometry's (QD) diagnostic efficacy and
      predictive value in discogenic-pain evaluation in a prospective study correlating
      intradiscal pressure values with pain reduction after percutaneous image-guided
      technique (i.e., percutaneous decompression, PD). MATERIALS AND METHODS: During
      the last 3 years, 36 patients [21 male and 15 female (mean age 36 +/- 5.8 years)]
      with intervertebral disc hernia underwent QD before PD. Under absolute
      sterilization and fluoroscopy, a mixture of contrast medium and normal saline
      (3:1 ratio) was injected. A discmonitor performed a constant rate injection and
      recorded pressure and volume values, thus producing the relative pressure-volume
      curve. PD was then performed. Pain reduction and improved mobility were recorded
      at 3, 12, and 24 months after PD using clinical evaluation and a numeric visual
      scale (NVS; 0 to 10 units). RESULTS: Mean pain values of 7.5 +/- 1.9 (range 4 to
      8) NVS units were recorded before PD; these decreased to 2.9 +/- 2.44 at 3
      months, 1.0 +/- 1.9 at 12 months, and 1.0 +/- 1.9 NVS units at 24 months after
      PD. Recorded correlations (pressure, volume, significant pain-reduction values)
      with bilateral statistical significance included a maximum injected volume of 2.4
      ml (p = 0.045), P (o) < 14 psi [initial pressure required to inject 0.1 ml of the
      mixture inside the disc (p = 0.05)], P (max) <= 65 psi [greatest pressure value
      on the curve (p = 0.018)], and P (max) - P (o) <= 47 psi (p = 0.038). Patients
      meeting these pressure or volume cut-off points, either independently or as a
      total, had significant pain reduction (>4 NVS units) after PD. No complications
      were noted. CONCLUSIONS: QD is an efficient technique that may have predictive
      value for discogenic pain evaluation. It might serve as a useful tool for patient
      selection for intervertebral disc therapies.

PMID- 21870209
TI  - Introduction to the special issue: toward diversity and cultural competence in
      genetic counseling.
AB  - This introduction provides an overview of the professional issues and original
      research papers in this special issue. The articles address workforce challenges
      and/or cross-cultural education and communication with culturally and religiously
      diverse clients. Additional suggestions are made for moving the profession of
      genetic counseling toward diversity and cultural competence.

PMID- 21870210
TI  - Case report: cauda equina syndrome associated with an interspinous device.
AB  - BACKGROUND: Although postoperative spinal epidural hematoma (SEH) is not
      uncommon, hematomas that require surgery are rare. Cauda equina syndrome (CES)
      may be associated with postoperative SEH. In these cases, early recognition and
      emergency decompression can prevent further damage and better neurologic
      recovery. CASE DESCRIPTION: A 41-year-old man underwent two-level discectomy with
      insertion of an interspinous spacer at L3-4 and L4-5 because of low back pain and
      radiculopathy. Eight hours after the operation, the patient developed CES. MRI
      revealed SEH compressing posteriorly at the L3-4 level. On emergency
      decompression and hematoma evacuation, the interspinous spacer had obstructed the
      laminotomy site at L3-4 completely, blocking drainage to the drain. The patient
      experienced complete neurologic recovery by 2 months followup. LITERATURE REVIEW:
      Many studies report risk factors for SEH. However, postoperative SEH can also be
      encountered in patients without these risks. One study reported a critical ratio
      (preoperative versus postoperative cross-sectional area) correlated with
      postoperative symptoms, especially in those with CES. The propensity to develop
      CES is likely dependent on a number of patient-specific factors. CLINICAL
      RELEVANCE: Surgeons should be aware that patients without risk factors may
      develop acute CES. Wider laminotomy (larger than half of the device size) may
      help to prevent this complication when one uses the compressible type of device,
      especially in patients with relatively small lamina.

PMID- 21870211
TI  - Imaging the impact of Nox4 in cycling hypoxia-mediated U87 glioblastoma invasion
      and infiltration.
AB  - PURPOSE: We determined the impact of the cycling hypoxia tumor microenvironment
      on tumor cell invasion and infiltration in U87 human glioblastoma cells and
      investigated the underlying mechanisms using molecular bio-techniques and
      imaging. PROCEDURES: The invasive phenotype of U87 cells and xenografts exposed
      to experimentally imposed cycling hypoxic stress in vitro and in vivo was
      determined by the matrigel invasion assay in vitro and dual optical reporter gene
      imaging in vivo. RNAi-knockdown technology was utilized to study the role of the
      NADPH oxidase subunit 4 (Nox4) on cycling hypoxia-mediated tumor invasion.
      RESULTS: Cycling hypoxic stress significantly promoted tumor invasion in vitro
      and in vivo. However, Nox4 knockdown inhibited this effect. Nox4-generated
      reactive oxygen species (ROS) are required for cycling hypoxia-induced invasive
      potential in U87 cells through the activation of NF-kappaB- and ERK-mediated
      stimulation of MMP-9. CONCLUSIONS: Cycling hypoxia-induced ROS via Nox4 should be
      considered for therapeutic targeting of tumor cell invasion and infiltration in
      glioblastoma.

PMID- 21870212
TI  - Delay discounting in rhesus monkeys: equivalent discounting of more and less
      preferred sucrose concentrations.
AB  - Humans discount larger amounts of a delayed reinforcer less steeply than smaller
      amounts, but studies with pigeons and rats have yet to reveal such a magnitude
      effect, suggesting that the effect may be unique to humans. The present study
      examined whether the magnitude effect is observed in a species phylogenetically
      closer to humans, by comparing the rates at which rhesus monkeys discounted 10%
      and 20% concentrations of sucrose. There were no systematic differences in the
      rates at which the monkeys discounted the two sucrose concentrations, despite the
      fact that they strongly preferred the 20% concentration. Interestingly, the
      monkeys discounted delayed sucrose at a rate higher than was observed with
      delayed cocaine, and lower than was observed with delayed saccharin in previous
      studies (Freeman et al. Behavioural Processes, 82, 214-218, 2009; Woolverton et
      al. Experimental and Clinical Psychopharmacology, 15, 238-244, 2007). Taken
      together, these findings suggest that although both quantitative and qualitative
      differences can affect monkeys' preferences between immediate reinforcers,
      qualitative differences between types of reinforcers (e.g., sucrose vs. cocaine)
      can affect monkeys' discounting rates in a way that quantitative differences
      within a reinforcer (e.g., 10% vs. 20% sucrose) do not.

PMID- 21870213
TI  - Reevaluating canine perspective-taking behavior.
AB  - Udell, Dorey, and Wynne (2011) demonstrated that both domesticated and
      nondomesticated canids-specifically, gray wolves-have the capacity to succeed on
      perspective-taking tasks, suggesting that dogs' ability to respond to the human
      attentional state is not a by-product of domestication alone. Furthermore, not
      all dogs were successful on the task. Instead, the occluder type used was a
      strong predictor of performance, indicating the important role of environment and
      experience for tasks of this type. Here, we address several commentaries
      reflecting on the methods and design of that study, as well as the interpretation
      of the results. We also discuss the positive shift toward more interactive
      approaches in the field of canine behavior and cognition. Finally, we question
      the functionality of describing canine social behavior in terms of theory of
      mind.

PMID- 21870214
TI  - Groundwater quality assessment in the village of Lutfullapur Nawada, Loni,
      District Ghaziabad, Uttar Pradesh, India.
AB  - The groundwater quality for drinking, domestic and irrigation in the village
      Lutfullapur Nawada, Loni, district Ghaziabad, U.P., India, has been assessed.
      Groundwater samples were collected, processed and analyzed for temperature, pH,
      conductivity, salinity, total alkalinity, carbonate alkalinity, bicarbonate
      alkalinity, total hardness, calcium hardness, magnesium hardness, total solids,
      total dissolved solids, total suspended solids, nitrate-nitrogen, chloride,
      fluoride, sulfate, phosphate, silica, sodium, potassium, calcium, magnesium,
      total chromium, cadmium, copper, iron, nickel, lead and zinc. A number of
      groundwater samples showed levels of electrical conductivity (EC), alkalinity,
      chloride, calcium, sodium, potassium and iron exceeding their permissible limits.
      Except iron, the other metals (Cr, Cd, Cu, Ni, Pb, and Zn) were analyzed below
      the permissible limits. The correlation matrices for 28 variables were performed.
      EC, salinity, TS and TDS had significant positive correlations among themselves
      and also with NO (3) (-) , Cl(-), alkalinity, Na(+), K(+), and Ca(2+). Fluoride
      was not significantly correlated with any of the parameters. NO (3) (-) was
      significantly positively correlated with Cl(-), alkalinity, Na(+), K(+) and
      Ca(2+). Chloride also correlated significantly with alkalinity, Na(+), K(+) and
      Ca(2+). Sodium showed a strong and positive correlation with K(+) and Ca(2+). pH
      was negatively correlated with most of the physicochemical parameters. This
      groundwater is classified as a normal sulfate and chloride type. Base-exchange
      indices classified 73% of the groundwater sources as the Na(+)-SO (4) (2-) type.
      The meteoric genesis indices demonstrated that 67% of groundwater sources belong
      to a deep meteoric water percolation type. Hydrochemical groundwater evaluations
      revealed that most of the groundwaters belong to the Na(+)-K(+)-Cl(-)-SO (4) (2-)
      type followed by Na(+)-K(+)-HCO (3) (-) type. Salinity, chlorinity and SAR
      indices indicated that majority of groundwater samples can be considered suitable
      for irrigation purposes.

PMID- 21870217
TI  - Supramolecular polymorphism of DNA in non-cationic Lalpha lipid phases.
AB  - The structure of a complex between hydrated DNA and a non-cationic lipid is
      studied, including its phase diagram. The complex is spontaneously formed by
      adding DNA fragments (ca. 150 base pairs in length) to non-cationic lipids and
      water. The self-assembly process often leads to highly ordered structures. The
      structures were studied by combining X-ray scattering, fluorescence and polarized
      microscopy, as well as freeze-fracture experiments with transmission electron
      microscopy. We observe a significant increase of the smectic order as DNA is
      incorporated into the water layers of the lamellar host phase, and stabilization
      of single phase domains for large amounts of DNA. The effect of confinement on
      DNA ordering is investigated by varying the water content, following three
      dilution lines. A rich polymorphism is found, ranging from weakly correlated DNA
      DNA in-plane organizations to highly ordered structures, where transmembrane
      correlations lead to the formation of columnar rectangular and columnar hexagonal
      superlattices of nucleotides embedded between lipid lamellae. From these
      observations, we suggest that addition of DNA to the lamellar phase significantly
      restricts membrane fluctuations above a certain concentration and helps the
      formation of the lipoplex. The alteration of membrane steric interactions,
      together with the appearance of interfacial interactions between membranes and
      DNA molecules may be a relevant mechanism for the emergence of highly ordered
      structures in the concentrated regime.

PMID- 21870218
TI  - Refining efficacy: allosterism and bias in G protein-coupled receptor signaling.
AB  - Receptors on the surface of cells function as conduits for information flowing
      between the external environment and the cell interior. Since signal transduction
      is based on the physical interaction of receptors with both extracellular ligands
      and intracellular effectors, ligand binding must produce conformational changes
      in the receptor that can be transmitted to the intracellular domains accessible
      to G proteins and other effectors. Classical models of G protein-coupled receptor
      (GPCR) signaling envision receptor conformations as highly constrained, wherein
      receptors exist in equilibrium between single "off" and "on" states distinguished
      by their ability to activate effectors, and ligands act by perturbing this
      equilibrium. In such models, ligands can be classified based upon two simple
      parameters; affinity and efficacy, and ligand activity is independent of the
      assay used to detect the response. However, it is clear that GPCRs assume
      multiple conformations, any number of which may be capable of interacting with a
      discrete subset of possible effectors. Both orthosteric ligands, molecules that
      occupy the natural ligand-binding pocket, and allosteric modulators, small
      molecules or proteins that contact receptors distant from the site of ligand
      binding, have the ability to alter the conformational equilibrium of a receptor
      in ways that affect its signaling output both qualitatively and quantitatively.
      In this context, efficacy becomes pluridimensional and ligand classification
      becomes assay dependent. A more complete description of ligand-receptor
      interaction requires the use of multiplexed assays of receptor activation and
      screening assays may need to be tailored to detect specific efficacy profiles.

PMID- 21870215
TI  - Fucose content of monoclonal antibodies can be controlled by culture medium
      osmolality for high antibody-dependent cellular cytotoxicity.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is dependent on the fucose
      content of oligosaccharides bound to monoclonal antibodies (MAbs). As MAbs with a
      low fucose content exhibit high ADCC activity, it is important to control the
      defucosylation levels (deFuc%) of MAbs and to analyze the factors that affect
      deFuc%. In this study, we observed that the deFuc% was inversely related to
      culture medium osmolality for MAbs produced in the rat hybridoma cell line YB2/0,
      with r (2) values as high as 0.92. Moreover, deFuc% exhibited the same
      correlation irrespective of the type of compound used for regulating osmolality
      (NaCl, KCl, fucose, fructose, creatine, or mannitol) at a culture scale ranging
      from 1 to 400 L. We succeeded in controlling MAb deFuc% by maintaining a constant
      medium osmolality in both perfusion and fed-batch cultures. In agreement with
      these observations, reverse transcription PCR analyses revealed decreased
      transcription of genes involved in glycolysis, GDP-fucose supply, and fucose
      transfer under hypoosmotic conditions.

PMID- 21870219
TI  - Imaging-based approaches to understanding g protein-coupled receptor signalling
      complexes.
AB  - In the last 10 years, imaging assays based on resonance energy transfer (RET) and
      protein fragment complementation have made it possible to study interactions
      between components of G protein-coupled receptor (GPCR) signalling complexes in
      living cells under physiological conditions. Here, we consider the history of
      such approaches, the current tools available and how they have changed our
      understanding of GPCR signalling. We also discuss some theoretical and
      methodological issues important when combining the different types of assay.

PMID- 21870220
TI  - Improving drug discovery with contextual assays and cellular systems analysis.
AB  - Despite rapid growth in our knowledge of potential disease targets following
      completion of the first drafts of the human genome over 10 years ago, the success
      rate of new therapeutic discovery has been frustratingly low. In addition to the
      widely reported costs and single-digit success rate of the entire drug discovery
      and development process, it has recently been estimated that even the preliminary
      process of transitioning new targets to preclinical development succeeds in less
      than 3% of attempts [Vogel (ed.) Drug Discovery and Evaluation: Pharmacological
      Assays. 3rd ed. Springer, Berlin (2007)]. At these early stages of development,
      poor understanding of therapeutic mechanisms and lack of compound selectivity are
      often to blame for failed compounds. It is worth noting than the emerging class
      of nucleic acid-based therapeutics, including miRNA and RNAi, are likely to be
      even more prone to unexpected system-wide and off-target activities. For all
      therapeutic approaches, it is clear that discovery strategies permitting the
      assessment of drug targets in their native context are required. At the same
      time, these strategies need to retain the high throughput of current reductionist
      approaches to enable broad assessment of chemical space for small molecule and
      genetic therapeutics. We describe here an integrated system based on high-content
      cellular analysis combined with system-wide pathway interrogation. The platform
      can be applied to novel therapeutic target and drug candidate identification, and
      for providing detailed mechanistic and selectivity information at an early stage
      of development.

PMID- 21870221
TI  - RGS-insensitive Galpha subunits: probes of Galpha subtype-selective signaling and
      physiological functions of RGS proteins.
AB  - The Regulator of G protein Signaling (RGS) proteins were identified as a family
      in 1996 and humans have more than 30 such proteins. Their best known function is
      to suppress G Protein-Coupled Receptors (GPCR) signaling by increasing the rate
      of Galpha turnoff through stimulation of GTPase activity (i.e., GTPase
      acceleration protein or GAP activity). The GAP activity of RGS proteins on the
      Galphai and Galphaq family of G proteins can terminate signals initiated by both
      alpha and betagamma subunits. RGS proteins also serve as scaffolds, assembling
      signal-regulating modules. Understanding the physiological roles of RGS proteins
      is of great importance, as GPCRs are major targets for drug development. The
      traditional method of using RGS knockout mice has provided some information about
      the role of RGS proteins but in many cases effects are modest, perhaps because of
      redundancy in RGS protein function. As an alternative approach, we have utilized
      a glycine-to-serine mutation in the switch 1 region of Galpha subunits that
      prevents RGS binding. The mutation has no known effects on Galpha binding to
      receptor, Gbetagamma, or effectors. Alterations in function resulting from the
      G>S mutation imply a role for both the specific mutated Galpha subunit and its
      regulation by RGS protein activity. Mutant rodents expressing these G>S mutant
      Galpha subunits have strong phenotypes and provide important information about
      specific physiological functions of Galphai2 and Galphao and their control by
      RGS. The conceptual framework behind this approach and a summary of recent
      results is presented in this chapter.

PMID- 21870222
TI  - Bioinformatic approaches to metabolic pathways analysis.
AB  - The growth and development in the last decade of accurate and reliable mass data
      collection techniques has greatly enhanced our comprehension of cell signaling
      networks and pathways. At the same time however, these technological advances
      have also increased the difficulty of satisfactorily analyzing and interpreting
      these ever-expanding datasets. At the present time, multiple diverse scientific
      communities including molecular biological, genetic, proteomic, bioinformatic,
      and cell biological, are converging upon a common endpoint, that is, the
      measurement, interpretation, and potential prediction of signal transduction
      cascade activity from mass datasets. Our ever increasing appreciation of the
      complexity of cellular or receptor signaling output and the structural
      coordination of intracellular signaling cascades has to some extent necessitated
      the generation of a new branch of informatics that more closely associates
      functional signaling effects to biological actions and even whole-animal
      phenotypes. The ability to untangle and hopefully generate theoretical models of
      signal transduction information flow from transmembrane receptor systems to
      physiological and pharmacological actions may be one of the greatest advances in
      cell signaling science. In this overview, we shall attempt to assist the
      navigation into this new field of cell signaling and highlight several
      methodologies and technologies to appreciate this exciting new age of signal
      transduction.

PMID- 21870223
TI  - Studying ligand efficacy at G protein-coupled receptors using FRET.
AB  - Drug "ligands" that bind G protein-coupled receptors (GPCRs) can either
      stimulate, fully (full agonists) or partially (partial agonists), or reduce
      (inverse agonists) basal receptor activity, by stabilizing different receptor
      conformations. The term "intrinsic efficacy" was introduced as a parameter to
      express the ability of a ligand to activate its receptor and to differentiate the
      varying signaling capacity of diverse ligands when they occupy the same fraction
      of a single receptor. Most methods use downstream biochemical and physiological
      responses as proxies of "intrinsic efficacy" but cannot measure it directly at
      the level of the receptor. Here I describe the development of a Forster resonance
      energy transfer (FRET) approach that permits the rigorous measurement of the
      intrinsic efficacy of a ligand directly at the level of a GPCR and independent
      from variation in experimental conditions. This approach also allows intrinsic
      efficacies of ligands to be linked with the effects of receptor polymorphisms or
      receptor heterodimerization.

PMID- 21870224
TI  - Using BRET to detect ligand-specific conformational changes in preformed
      signalling complexes.
AB  - Bioluminescence energy transfer (BRET) has become a powerful tool to study
      protein-protein interactions and conformational changes among interacting
      proteins. In particular, BRET assays performed in living cells have revealed that
      heptahelical receptors (7TMRs), heterotrimeric G proteins and their proximal
      effectors form constitutive signalling complexes. BRET technology has also
      allowed us to demonstrate that these multimeric protein arrays remain intact
      throughout initial stages of receptor signalling, thus providing a platform for
      direct transmission of conformational information from activated receptors to
      downstream signalling partners. A clear example of the latter are the distinct
      intermolecular re-arrangements undergone by 7TMRs and G protein subunits
      following activation of the receptor by different ligands. Here we present
      protocols describing the type of BRET assay that has been used to reveal the
      existence of constitutive signalling arrays formed by 7TMRs and proximal
      signalling partners as well as the ability of complex components to undergo
      ligand-specific conformational changes.

PMID- 21870226
TI  - Using quantitative BRET to assess G protein-coupled receptor homo- and
      heterodimerization.
AB  - Over a period of 15 years the concept of G protein-coupled receptor (GPCR)
      dimerization moved from a challenging hypothesis to a scientific fact, which is
      now accepted by the vast majority of the scientists working in the field.
      However, several important issues remain debated such as the biological function
      of dimerization, or the actual complexity of the oligomeric organization. Because
      of its major potential implications in physiology and pharmacology, the question
      of GPCR heterodimerization (or hetero-oligomerization) is currently one of the
      most central. Several complementary experimental approaches are used to
      investigate these novel important aspects of GPCR biology. In this context,
      Bioluminescence Resonance Energy Transfer-based techniques are extremely
      powerful, provided that they are conducted with the appropriate (numerous)
      controls and correctly interpreted.

PMID- 21870225
TI  - Reconstitution of G protein-coupled receptors into a model bilayer system:
      reconstituted high-density lipoprotein particles.
AB  - Reconstituted high-density lipoprotein particles (rHDL) are powerful platforms
      used as a model phospholipid bilayer system to study membrane proteins. They
      consist of a discoidal-shaped planar bilayer of phospholipids that is surrounded
      by a dimer of apolipoprotein A-I (apoA-I). The amphipathic nature of apoA-1
      shields the hydrophobic acyl chains of the lipids from solvent and keeps the
      particles soluble in aqueous environments. These monodispersed, nanoscale
      discoidal HDL particles are approximately 10-11 nm in diameter with a thickness
      that is dependent on the length of the phospholipid acyl chain. Reconstituted HDL
      particles can be assembled in vitro using purified apoA-1 and purified lipids.
      Investigators have utilized this model bilayer system to co-reconstitute membrane
      proteins, and take advantage of the small size and its monodispersion. Our
      laboratory and others have utilized the rHDL approach to study the behavior of G
      protein-coupled receptors. In this chapter, we describe strategies for the
      preparation of rHDL particles containing GPCRs in their monomeric form and
      discuss various methodologies used to analyze the reconstituted receptor
      function.

PMID- 21870227
TI  - Cell-surface protein-protein interaction analysis with time-resolved FRET and
      snap-tag technologies: application to G protein-coupled receptor oligomerization.
AB  - G protein-coupled receptors (GPCRs) are key players in cell-cell communication,
      the dysregulation of which has often deleterious effects leading to pathologies
      such as psychiatric and neurological diseases. Consequently, GPCRs represent
      excellent drug targets, and as such are the object of intense research in drug
      discovery for therapeutic application. Recently, the GPCR field has been
      revolutionized by the demonstration that GPCRs are part of large protein
      complexes that control their pharmacology, activity, and signaling. Moreover, in
      these complexes, one GPCR can either associate with itself, forming homodimers or
      homooligomers, or with other receptor types, forming heterodimeric or
      heterooligomeric receptor entities that display new receptor features. These
      features include alterations in ligand cooperativity and selectivity, the
      activation of novel signaling pathways, and novel processes of desensitization.
      Thus, it has become necessary to identify GPCR-associated protein complexes of
      interest at the cell surface, and to determine the state of oligomerization of
      these receptors and their interactions with their partner proteins. This is
      essential to understand the function of GPCRs in their native environment, as
      well as ways to either modulate or control receptor activity with appropriate
      pharmacological tools, and to develop new therapeutic strategies. This requires
      the development of technologies to precisely address protein-protein interactions
      between oligomers at the cell surface. In collaboration with Cisbio Bioassay, we
      have developed such a technology, which combines TR-FRET detection with a new
      labeling method called SnapTag. This technology has allowed us to address the
      oligomeric state of many GPCRs.

PMID- 21870228
TI  - Analysis of GPCR/ion channel interactions.
AB  - Voltage-gated calcium channels are key regulators of calcium homeostasis in
      excitable cells. A number of cellular signaling pathways serve to fine tune
      calcium channel activity, including the activation of G protein-coupled
      receptors. Besides regulating channel activity via second messengers, GPCRs can
      also physically associate with calcium channels to directly regulate their
      functions, as well as their trafficking to and from the plasma membrane. Here we
      provide some methods that can be used to examine channel-receptor interactions
      and co-trafficking. While we focus on voltage-gated calcium channels, the
      techniques described herein are broadly applicable to other types of channels.

PMID- 21870230
TI  - Real-time BRET assays to measure G protein/effector interactions.
AB  - Advances in imaging assays based on resonance energy transfer (RET) have made it
      possible to study protein/protein interactions in living cells under
      physiological conditions. It is now possible to measure the kinetics of changes
      in these interactions in response to ligand stimulation in real time. Here we
      describe protocols for these assays focusing on the basal and ligand-stimulated
      interaction between tagged Gbetagamma subunits and adenylyl cyclase II. We
      describe relevant positive and negative controls and various experimental
      considerations for optimization of these experiments.

PMID- 21870229
TI  - Multicolor BiFC analysis of G protein betagamma complex formation and
      localization.
AB  - Cells co-express multiple G protein beta and gamma subunit isoforms, but the
      extent to which individual subunits associate to form particular betagamma
      complexes is not known. This issue is important because in vivo knockout
      experiments suggest that specific betagamma complexes may have unique functions
      despite the fact that most complexes exhibit similar properties when assayed in
      reconstituted systems. This chapter describes how multicolor bimolecular
      fluorescence complementation (BiFC) can be used in living cells to study the
      association preferences of beta and gamma subunits. Multicolor BiFC determines
      the association preferences of these subunits by quantifying the two fluorescent
      complexes formed when beta or gamma subunits fused to amino terminal fragments of
      yellow fluorescent protein (YFP-N) and cyan fluorescent protein (CFP-N) compete
      for interaction with limiting amounts of a common gamma or beta subunit,
      respectively, fused to a carboxyl terminal fragment of CFP (CFP-C). One means by
      which betagamma complexes may differ from each other and thereby mediate unique
      functions in vivo is in the kinetics and patterns of their internalization
      responses to stimulation of G protein-coupled receptors (GPCRs). Methods are
      described for imaging and quantifying the internalization of pairs of betagamma
      complexes in response to GPCR stimulation in living cells.

PMID- 21870231
TI  - Luminescent biosensors for real-time monitoring of intracellular cAMP.
AB  - G-protein coupled, seven-transmembrane (7-TM) receptors (GPCRs) comprise a
      diverse class of signaling molecules involved in cellular physiology and
      pathology. In recent years, intracellular biosensors have been developed to
      monitor changes in intracellular cAMP in real time, facilitating studies on the
      mechanisms of GPCR activation and desensitization in living cells. However,
      methods based on fluorescence can show limitations in response dynamics together
      with being difficult to perform. Here we present the use of genetically encoded,
      luminescent biosensors that allow a facile, non-lytic assay format for monitoring
      cAMP dynamics in living cells.

PMID- 21870232
TI  - Simultaneous real-time imaging of signal oscillations using multiple fluorescence
      based reporters.
AB  - It is now well understood that G protein-coupled receptor (GPCR)-mediated cell
      signalling is subject to extensive spatial-temporal control, and that a
      meaningful understanding of this complexity requires techniques to study
      signalling at the molecular and sub-cellular level. This complexity in cell
      signal pattern begins with ligand binding to the receptor and its coupling to a
      variety of different effector systems. These signal transduction cascades within
      a cell involve a very complex series of molecular events requiring the generation
      of multiple second messenger responses and the activation a multiple effector
      proteins. In the present chapter, we will describe methodology for the
      simultaneous assessment of the spatial-temporal measurement of increases in
      intracellular Ca2+ concentrations and the activation of protein kinase C (PKC) in
      response to the agonist activation of a Galphaq/11-coupled GPCR. Specifically, we
      will describe a confocal imaging approach to simultaneously measure
      oscillilations in intracellular Ca2+ levels and PKC translocation to the plasma
      membrane in response to mGluR1 stimulation in transiently transfected human
      embryonic kidney (HEK293) cells. The changes in intracellular Ca2+ were imaged
      using the fluorescent indicator Oregon Green 488 BAPTA and a recombinant
      PKCbetaII-DsRed fusion protein was used to image the sub-cellular distribution of
      the PKCbetaII isoform.

PMID- 21870233
TI  - Using FRET-based reporters to visualize subcellular dynamics of protein kinase A
      activity.
AB  - The ubiquitous Protein Kinase A (PKA) signaling pathway is responsible for the
      regulation of numerous processes including gene expression, metabolism, cell
      growth, and cell proliferation. This method details how to monitor real-time PKA
      activity dynamics in mammalian cells using fluorescence resonance energy transfer
      (FRET)-based reporters.

PMID- 21870234
TI  - Genetically encoded fluorescent reporters to visualize protein kinase C
      activation in live cells.
AB  - Protein kinase C (PKC) signaling drives many important cellular processes and its
      dysregulation results in pathophysiologies such as cancer (Gokmen-Polar et al.,
      Cancer Res 61:1375-1381, 2001). Because PKC is activated acutely and
      allosterically, it is difficult to monitor the cellular activity of endogenous
      PKC by conventional methodologies (Newton, Methods Enzymol 345:499-506, 2002).
      Rather, PKC signaling is best studied in situ using biosensors such as FRET-based
      reporters. We have generated several FRET-based reporters for studying PKC
      signaling in real time in live cells (Violin and Newton, IUBMB Life 55:653-660,
      2003). Using these reporters, we have demonstrated phase-locked oscillations in
      Ca2+ release and membrane-localized endogenous PKC activity in response to
      histamine (Violin et al., J Cell Biol 161:899-909, 2003), as well as distinct
      signatures of endogenous PKC signaling at specific organelles in response to
      uridine-5'-triphosphate (UTP; Gallegos et al., J Biol Chem 281:30947-30956,
      2006). Here we describe methods to image cells expressing the reporters and
      elaborate on data analyses, control experiments, and variations for imaging the
      activity of expressed PKC.

PMID- 21870235
TI  - Visualizing receptor endocytosis and trafficking.
AB  - G-protein-coupled 7 transmembrane domain receptors (GPCR-7TMR) represent the
      largest class of membrane protein drug targets. They respond to a plethora of
      ligands ranging from small molecules to polypeptide hormones. Upon activation,
      almost all GPCR-7TMRs undergo desensitization followed by receptor
      internalization and resensitization. This cycle is crucially important for
      regulating the signal emanating from the receptor and is tightly linked to the
      receptor and/or the ligands studied. In this chapter, we describe some of the
      technical approaches that can be used to study GPCR internalization and
      trafficking.

PMID- 21870236
TI  - Investigating G protein-coupled receptor endocytosis and trafficking by TIR-FM.
AB  - G protein-coupled receptors (GPCRs) represent the largest and most versatile
      family of signaling receptors. Their actions are highly regulated, both under
      physiological conditions and in response to clinically relevant drugs. A key
      element in this regulation is control of the number of functional receptors at
      the cell surface. Major processes that mediate this regulation are vesicular
      endocytosis and exocytosis of receptors. These trafficking events involve a
      concerted series of steps, some of which occur on a rapid timescale similar to
      that of functional signaling itself. Here, we describe and discuss an optical
      imaging approach, based on evanescent field or total internal reflection
      fluorescence microscopy (TIR-FM), to investigate receptor endocytosis and
      recycling at the level of discrete membrane fission and fusion events. TIR-FM
      facilitates the study of receptor trafficking events near the plasma membrane
      with much greater spatial and temporal resolution than afforded by traditional
      methods. TIR-FM has already provided new insight to GPCR regulation, and we
      believe that this method has great potential for addressing a variety of
      questions in GPCR biology.

PMID- 21870237
TI  - Visualizing G protein-coupled receptor signalsomes using confocal
      immunofluorescence microscopy.
AB  - The heptahelical G protein-coupled receptors (GPCRs) receive and transmit a wide
      range of extracellular stimuli and induce a wide array of cellular responses by
      activating signaling kinases. It has become increasingly evident that the agonist
      stimulated GPCR complexed with the adaptor protein, beta-arrestin, serves as a
      focal point to recruit, activate, and target kinases to discrete subcellular
      compartments. This chapter describes a protocol to visualize the changes in the
      subcellular distribution of activated extracellular signal-regulated kinases 1
      and 2 (ERK1/2) when induced by the angiotensin II type 1a receptor.

PMID- 21870238
TI  - Detection and characterization of receptor interactions with PDZ domains.
AB  - Many transmembrane receptors are regulated by associations with scaffold proteins
      containing PDZ domains, which interact with receptor carboxyl-termini to control
      receptor signaling, trafficking, and localization. We describe here approaches
      for detecting and characterizing interactions between receptors and PDZ
      scaffolds. These approaches include the construction and screening of proteomic
      arrays, blot overlays using fusion proteins, and co-immunoprecipitation studies
      to assess interactions in cells.

PMID- 21870239
TI  - Tandem affinity purification and identification of heterotrimeric g protein
      associated proteins.
AB  - Heterotrimeric G proteins are the main signal-transducing molecules activated by
      G protein-coupled receptors. Their GTP-dependent activation leads to the
      regulation of different effectors such as adenylyl cyclases, phospholipases, and
      RhoGEFs. To understand the full biological consequences of GPCR signalling and to
      further understand the cross-talk with other signalling pathways, the complement
      of proteins associating with heterotrimeric G proteins needs to be identified.
      Here we describe our mass spectrometry-based proteomic approaches for the study
      of Gbetagamma and Galpha protein complexes. This approach is predicated on the
      establishment of mammalian cell lines constitutively or inducibly expressing
      affinity-tagged versions of Gbetagamma or wild-type and constitutively active
      Galpha subunits, respectively.

PMID- 21870240
TI  - Study of G protein-coupled receptor/beta-arrestin interactions within endosomes
      using FRAP.
AB  - beta-arrestins, through their scaffolding functions, are key regulators of G
      protein-coupled receptor (GPCR) signaling and intracellular trafficking. However,
      little is known about the dynamics of beta-arrestin/receptor interactions and how
      these complexes, and complexes with other regulatory proteins, are controlled in
      cells. Here, we use yellow fluorescent protein (YFP)-tagged beta-arrestin 2 and a
      fluorescence recovery after photobleaching (FRAP) imaging approach to probe the
      real-time interaction of beta-arrestin with a GPCR, the bradykinin type 2
      receptor (B2R). We provide a detailed protocol to assess the avidity of beta
      arrestin2-YFP for B2R within endosomes in HEK293 cells. beta-arrestin2-YFP
      associated with internalized receptors is photobleached with intense light, and
      fluorescence recovery due to the entry of nonbleached beta-arrestin2-YFP is
      monitored over time as a measure of the rate exchange of beta-arrestin2-YFP
      within the endosome. This approach can be extended to other GPCR/beta-arrestin
      complexes and their putative regulators to provide information about the kinetics
      of similar protein-protein interactions in cells. Moreover, these techniques
      should provide insight into the role of beta-arrestins in the intracellular
      trafficking and signaling of GPCRs.

PMID- 21870241
TI  - Disrupting protein complexes using Tat-tagged peptide mimics.
AB  - Protein-protein interaction is a widely existing phenomenon and is essential for
      almost all biological processes, extending from the formation of cellular
      macromolecular structures and enzymatic complexes to the regulation of signal
      transduction pathways. Proteins interact with each other through the dynamic
      associations between modular protein domains within different cellular
      compartments and with distinct temporal dynamics. Disrupting protein interactions
      has emerged as an effective way to specifically modulate certain signaling
      pathways. Tat-tagged peptide mimics are a recently developed experimental tool
      that is used to disrupt specific interactions between protein complexes. TAT, an
      11-amino acid protein transduction domain from HIV Tat protein, is tagged to
      peptides that mimic the functional fragment of protein interaction domains, and
      facilitates the delivery of peptides into cells to disrupt the associated protein
      both competitively and selectively. Here we provide a technical description on
      the utilization of Tat-tagged peptide mimics as a tool to disrupt protein
      interaction in cultured neurons and in the rat brain.

PMID- 21870242
TI  - Protein-fragment complementation assays for large-scale analysis, functional
      dissection and dynamic studies of protein-protein interactions in living cells.
AB  - Protein-fragment Complementation Assays (PCAs) are a family of assays for
      detecting protein-protein interactions (PPIs) that have been developed to provide
      simple and direct ways to study PPIs in any living cell, multicellular organism,
      or in vitro. PCAs can be used to detect PPI between proteins of any molecular
      weight and expressed at their endogenous levels. Proteins are expressed in their
      appropriate cellular compartments and can undergo any posttranslational
      modification or degradation that, barring effects of the PCA fragment fusion,
      they would normally undergo. Assays can be performed in any cell type or model
      organism that can be transformed or transfected with gene expression DNA
      constructs. Here we focus on recent applications of PCA in the budding yeast,
      Saccharomyces cerevisiae, that cover the gamut of applications one could envision
      for studying any aspect of PPIs. We present detailed protocols for large-scale
      analysis of PPIs with the survival-selection dihydrofolate reductase (DHFR),
      reporter PCA, and a new PCA based on a yeast cytosine deaminase reporter that
      allows for both survival and death selection. This PCA should prove a powerful
      way to dissect PPIs. We then present methods to study spatial localization and
      dynamics of PPIs based on fluorescent protein reporter PCAs.

PMID- 21870243
TI  - Blastocystis infection is associated with irritable bowel syndrome in a Mexican
      patient population.
AB  - In recent times, some common "non-pathogenic" parasites, such as Blastocystis and
      Dientamoeba fragilis, have been associated to the aetiology of irritable bowel
      syndrome (IBS), while host pro-inflammatory cytokine gene polymorphisms might
      have a role in the pathophysiology of the disease. Therefore, Blastocystis
      subtypes (ST), D. fragilis and gene promoter single nucleotide polymorphisms of
      interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in IBS patients
      and controls were studied. After giving written consent, 45 patients with
      symptoms of IBS according to the Rome III criteria and 45 controls were enrolled.
      DNA was extracted from peripheral blood for SNP analysis at position -174 for IL
      6 as well as -238 and -308 for TNF-alpha. Blastocystis was more common in the IBS
      group (p = 0.043). Interestingly, D. fragilis was found more frequently in the
      control group (p = 0.002); Blastocystis ST1 and 3 were most frequent in both
      groups. Haploview analysis revealed linkage disequilibrium in TNF-alpha (p <
      0.0001); however, none of the SNPs for IL-6 and TNF-alpha were found to be
      significantly related with IBS. The clinical and molecular approaches undertaken
      for the first time in Latin American IBS patients demonstrated an association
      with Blastocystis that supports a pathogenic role of this parasite in IBS
      Furthermore, co-infections with ST1 and ST3 were frequent; thus, the genetic
      diversity proposed within ST polymorphisms does not rule out that particular
      strains might be associated with disease. In addition, our results do not support
      a major contribution of IL-6 and TNF-alpha gene polymorphisms in the
      susceptibility to IBS.

PMID- 21870245
TI  - Clinical case of cerebral amebiasis caused by E. histolytica.
AB  - Although amebic brain abscess is a rare form of invasive amebiasis, when present,
      it is frequently lethal. This disorder always begins with the infection of the
      colon by Entamoeba histolytica trophozoites, which then travel to extra
      intestinal tissues through the bloodstream. Amebic brain abscesses are produced
      when trophozoites invade the central nervous system. Computerized axial
      tomography scans can be used to diagnose the presence or absence of a brain
      abscess with a certainty of 100%. However, this diagnostic tool does not reveal
      the etiological agent of disease. By analyzing the clinical case of a patient
      that died due to untimely treatment of this malady, the present study aims to
      identify a diagnostic tool that can give a precise determination of the
      etiological agent and therefore permit adequate and opportune treatment.
      Currently, diagnosis of amebic brain abscess is often done by identification of
      the ameba in a biopsy or autopsy. By immunohistochemistry and immunofluorescence
      with specific antibodies, we identified the existence of E. histolytica, which
      presents proteins similar to Naegleria fowleri in its membrane.

PMID- 21870246
TI  - Novel relapsing fever Borrelia detected in African penguins (Spheniscus demersus)
      admitted to two rehabilitation centers in South Africa.
AB  - The African penguin, Spheniscus demersus, the only penguin species that breeds in
      Africa, is endangered, and several diseases including avian malaria, babesiosis,
      and aspergillosis are common in some populations. From 2002 to 2010, spirochetes
      morphologically consistent with Borrelia were observed on thin blood smears from
      115 of 8,343 (1.4%) African penguins admitted to rehabilitation centers in the
      Western Cape and Eastern Cape provinces of South Africa. Prevalence rates were
      significantly higher among chicks and juveniles compared with adults and for
      birds sampled during the summer months of October to February compared with
      winter months. The majority of infected birds were ultimately released, despite
      lack of antibiotic treatment; however, at least one bird is believed to have died
      of borreliosis based on characteristic gross and microscopic lesions. Analysis of
      partial flaB gene sequences indicated this was a relapsing fever Borrelia most
      similar to a Borrelia sp. detected in soft ticks from a seabird colony in Japan.
      This represents the fourth report of a relapsing fever Borrelia sp. in an avian
      species and highlights the need for additional studies of potentially pathogenic
      organisms infecting the African penguin in South Africa.

PMID- 21870244
TI  - Characterization of Baylisascaris schroederi from Qinling subspecies of giant
      panda in China by the first internal transcribed spacer (ITS-1) of nuclear
      ribosomal DNA.
AB  - In the present study, a total of 20 nematode isolates, (including 10 male and 10
      female worms) representing Baylisascaris schroederi from 5 Qinling subspecies of
      giant pandas (Ailuropoda melanoleuca) in Shaanxi Province of China, were
      characterized and grouped genetically by the first internal transcribed spacer
      (ITS-1) of nuclear ribosomal DNA (rDNA). The rDNA fragment spanning 3' end of 18S
      rDNA, complete ITS-1 rDNA, and 5' end of 5.8S rDNA were amplified and sequenced.
      The sequence variability in ITS-1 rDNA was examined within B. schroederi and
      among parasites in order Ascaridata available in GenBankTM, and their
      phylogenetic relationships were also reconstructed. The sequences of ITS-1 rDNA
      for all the B. schroederi isolates were 427 bp in length, with no genetic
      variation detected among these isolates. Phylogenetic analyses based on the ITS-1
      rDNA sequences revealed that all the male and female B. schroederi isolates
      sequenced in the present study were posited into the clade of genus
      Baylisascaris, sistered to zoonotic nematodes in genus Ascaris, and the ITS-1
      rDNA sequence could distinguish different species in order Ascaridata. These
      results showed that the ITS-1 rDNA provides a suitable molecular marker for the
      inter-species phylogenetic analysis and differential identification of nematodes
      in order Ascaridata.

PMID- 21870247
TI  - Water availability modifies tolerance to photo-oxidative pollutants in
      transplants of the lichen Flavoparmelia caperata.
AB  - The hypothesis that a daily water supply allows a lichen to endure the negative
      effects of environmental concentrations of NO(x) and O(3) was tested with a
      transplant experiment. Five groups (0, A-D) of Flavoparmelia caperata samples
      derived from the same thalli were used for destructive, pre-exposure measurements
      (0), or exposed for 5 weeks in the rural collection site (A), and in a urban site
      with high levels of NO(x) and O(3) (B-D). Two groups (C, D) were daily watered
      half an hour before the daily peak of NO(x) (C), and O(3) (D). The comparison
      between pre- and post-exposure measurements of stress biomarkers revealed that
      the different thallus hydration regime modified the pollution tolerance as well
      as the physiology of the exposed samples. The non-watered group B suffered an
      evident decrease in F(v)/F(m) and reduced glutathione, but increased ion leakage,
      whereas the watered groups C and D showed only decreased non-photosynthetic
      quenching, possibly derived from NO(x) exposure. Ozone, which was higher in the
      rural than in the urban site, did not significantly affect the lichen metabolism.
      Our results re-open the discussion on the so-called "drought hypothesis", which
      suggests that the lichen desert observed in urban areas of central and eastern
      Europe is more a matter of dry microclimate than of air pollution.

PMID- 21870248
TI  - Coordination of Id1 and p53 activation by oxidized LDL regulates endothelial cell
      proliferation and migration.
AB  - Considering that oxidized low-density lipoprotein (ox-LDL) may inhibit
      endothelial cell (EC) migration and proliferation during endothelialization, we
      hypothesize that the Id1 protein promotes endothelialization exposed to ox-LDL.
      Cell proliferation was evaluated by cell counts, and cell migration was evaluated
      by wound closure assay. The role of Id1 in the cell migration and proliferation
      was appraised through building Id1 overexpression and silencing ECs. Here, we
      report that Id1 in human umbilical vascular ECs (HUVECs) was up-regulated by ox
      LDL in a dose- and time-dependent manner. Low concentrations of ox-LDL increased
      the proliferation and migration of EC. High concentrations of ox-LDL suppressed
      HUVECs proliferation and migration, whose inhibitory effects were abolished by
      Id1 over-expression. Attenuated proliferation and migration of ECs exposed to
      high concentrations of ox-LDL may be correlated with the nuclear localization of
      p53, which was obviously weakened by over-expression of Id1 and strengthened by
      silencing Id1. Collectively, changes in EC, comprising proliferation and
      migration, upon exposure to various concentrations of ox-LDL are, at least in
      part, attributed to the modulatory effect of the Id1 protein, which suggests that
      manipulating Id1 protein activity may offer therapeutic opportunities to promote
      re-endothelialization under high concentrations of ox-LDL.

PMID- 21870249
TI  - Effects of bracing on human kinematics in low-speed frontal sled tests.
AB  - Continued development of computational models and biofidelic anthropomorphic test
      devices (ATDs) necessitates further analysis of the effects of bracing on an
      occupant's biomechanical response in automobile collisions. A total of 20 dynamic
      sled tests were performed, 10 low (2.5 g, Deltav = 4.8 kph) and 10 medium
      severity (5.0 g, Deltav = 9.7 kph), with five male human volunteers of
      approximately 50th percentile male height and weight. Each volunteer was exposed
      to two impulses at each severity, one relaxed and one braced prior to the
      impulse. A Vicon motion analysis system, 12 MX-T20 2 megapixel cameras, was used
      to quantify subject 3D kinematics (+/-1 mm) (1 kHz). Excursions of select
      anatomical regions were normalized to their respective initial positions and
      compared by test condition. At the low severity, bracing significantly reduced (p
      < 0.05) the forward excursion of the knees, hips, elbows, shoulders, and head
      (average 35-70%). At the medium severity, bracing significantly reduced (p <
      0.05) the forward excursion of the elbows, shoulders, and head (average 36-69%).
      Although not significant, bracing at the medium severity considerably reduced the
      forward excursion of the knees and hips (average 18-26%). This study illustrates
      that bracing has a significant influence on the biomechanical response of human
      occupants in frontal sled tests and provides novel biomechanical data that can be
      used to refine and validate computational models and ATDs used to assess injury
      risk in automotive collisions.

PMID- 21870250
TI  - Characterization of MtnE, the fifth metallothionein member in Drosophila.
AB  - Metallothioneins (MTs) constitute a family of cysteine-rich, low molecular weight
      metal-binding proteins which occur in almost all forms of life. They bind
      physiological metals, such as zinc and copper, as well as nonessential, toxic
      heavy metals, such as cadmium, mercury, and silver. MT expression is regulated at
      the transcriptional level by metal-regulatory transcription factor 1 (MTF-1),
      which binds to the metal-response elements (MREs) in the enhancer/promoter
      regions of MT genes. Drosophila was thought to have four MT genes, namely, MtnA,
      MtnB, MtnC, and MtnD. Here we characterize a new fifth member of Drosophila MT
      gene family, coding for metallothionein E (MtnE). The MtnE transcription unit is
      located head-to-head with the one of MtnD. The intervening sequence contains four
      MREs which bind, with different affinities, to MTF-1. Both of the divergently
      transcribed MT genes are completely dependent on MTF-1, whereby MtnE is
      consistently more strongly transcribed. MtnE expression is induced in response to
      heavy metals, notably copper, mercury, and silver, and is upregulated in a
      genetic background where the other four MTs are missing.

PMID- 21870251
TI  - Approaches to detect PARP-1 activation in vivo, in situ, and in vitro.
AB  - An accurate and sensitive detection of catalytic activation of poly(ADP-ribose)
      polymerase-1 (PARP-1) is required to be performed in a wide variety of samples
      because this activity plays a role in various cellular responses to DNA damage
      ranging from DNA repair to cell death, as well as in housekeeping functions, such
      as transcription. Since PARP-1 gene is expressed constitutively, its activation
      cannot be surmised from increased expression of its mRNA or protein, but by
      demonstrating the consequences of its catalytic -reaction which results in
      consumption of the substrate nicotinamide adenine dinucleotide (NAD(+)) and
      formation of three products, namely, polymer of ADP-ribose (pADPr or PAR),
      nicotinamide, and protons. Here, we describe various approaches commonly used in
      our laboratory for detection of PARP-1 activation in vivo (cells, tissues, and
      tumors), in situ, and in vitro via assessment of formation of pADPr, depletion of
      the substrate NAD, or formation of protons resulting in rapid and reversible
      intracellular acidification. It is important to note that although some other
      members of the PARP family can carry out the same catalytic reaction, many of
      these assays largely reflect PARP-1 activation in a vast majority of the
      experimental circumstances and more specifically in DNA damage responses.
      However, if required, PARP-1-specific action should be confirmed by use of PARP-1
      knockout or RNAi-mediated knockdown approaches.

PMID- 21870252
TI  - Quantification of poly(ADP-ribose) in vitro: determination of the ADP-ribose
      chain length and branching pattern.
AB  - The structural integrity of eukaryotic genomes, to a great extent, depends on
      highly regulated and -coordinated enzymatic chromosomal poly(ADP-ribosyl)ation
      cycles that target chromatin proteins for specific covalent epigenetic poly(ADP
      ribose) modification. As a result, the accurate determination of poly(ADP
      ribosyl)ation amino acid specificity, as well as, a detailed characterization of
      the structural -complexity of the protein-bound ADP-ribose polymers generated,
      e.g., linear versus branched ADP-ribose chains, need to be carefully sorted out.
      In this chapter, we describe well-established and reproducible laboratory methods
      and protocols typically used to determine: (1) the ADP-ribose chain length(s) and
      (2) the molecular stoichiometry of the protein-poly(ADP-ribosyl)ation reaction,
      e.g., number of ADP-ribose chains/polypeptide unit. While the methodology
      described here is exclusively for in vitro purified systems that can be used with
      high reliability, the reader is advised that application of these protocols to
      whole cell extracts and tissue systems must take into consideration the rapid
      turnover rate of protein-bound ADP-ribose polymers in vivo. Indeed, these
      extremely low-abundance chromatin-bound polymeric molecules are notoriously
      characterized for displaying a short half-life, typically from a few seconds to a
      few minutes. We also discuss potential methodological pitfalls, such as: (1) the
      chemical stability of protein-(ADP-ribose)n adducts and (2) the requirement for
      polymeric radiolabeling.

PMID- 21870253
TI  - Assay for protein modification by poly-ADP-ribose in vitro.
AB  - The enzymatic function of poly(adenosine diphosphate (ADP)-ribose) polymerase
      (PARP) is central to many of its function as a component of DNA repair machinery,
      modulator of gene transcription, and cell differentiation. While the auto
      modification domain of PARP has been shown to be a primary acceptor site of poly
      ADP ribose (pADPr), other DNA binding nuclear proteins are also modified by
      pADPr. It is -generally accepted that pADPr polymer is built upon the carboxyl
      side chain of specific Glu, Asp, and/or Lys residues within the target protein.
      Identification of the unique amino acid acceptors of pADPr in these nuclear
      proteins is an active area of study. Because of the heterogeneity of pADPr chain
      on modified -protein targets, the resulting modified proteins have unpredictable
      final masses, making it difficult to -identify acceptor amino acids. Using
      recombinant proteins, in vitro pADP ribosylation assay and mass spectrometry, we
      have been able to identify conserved Glu residue in transcription factor NFAT
      that is enzymatically modified in vitro with pADPr by PARP-1. We discuss this
      protocol here as a model approach for identifying pADPr acceptors in other
      nuclear proteins.

PMID- 21870254
TI  - Identification of distinct amino acids as ADP-ribose acceptor sites by mass
      spectrometry.
AB  - ADP-ribosylation is a well-known post-translational protein modification, which
      regulates a variety of -cellular processes. The proteins able to catalyze mono-
      or poly ADP-ribosylation of proteins belong to the family of ADP
      ribosyltransferases. A variety of nuclear proteins has been described to be ADP
      ribosylated, including ARTD1 itself and histone proteins. Despite intensive
      research during the last 40 years, the acceptor amino acids in ARTD1 or histone
      proteins could be identified and confirmed only recently by MS/MS and by site
      directed mutagenesis. The establishment of a standardized protocol including the
      specific enrichment of ADP-ribosylated proteins and peptides and subsequent mass
      spectrometric analysis allows the identification of ADP-ribose acceptor sites of
      modified proteins and to address the functional contribution of ADP-ribosylation
      in vitro as well as in vivo.

PMID- 21870255
TI  - Noncovalent protein interaction with poly(ADP-ribose).
AB  - Compared to most common posttranslational modifications of proteins, a
      peculiarity of poly(ADP-ribosyl)ation is the molecular heterogeneity and
      complexity of the reaction product, poly(ADP-ribose) (PAR). In fact, protein
      bound PAR consists of variously sized (2-200 ADP-ribose residues) linear or
      branched molecules, negatively charged at physiological pH. It is now clear that
      PAR not only affects the function of the polypeptide to which it is covalently
      bound, but it can also influence the activity of other proteins by engaging
      specific noncovalent interactions. In the last 10 years, the family of PAR
      binding proteins has been rapidly growing and functional studies have expanded
      the regulatory potential of noncovalent -protein targeting by PAR far beyond
      initial assumptions.In this chapter, methods are described for: (1) PAR synthesis
      and analysis; (2) detecting PAR-binding proteins in protein mixtures; (3)
      defining affinity and specificity of PAR binding to individual proteins or
      protein fragments; and (4) identifying PAR molecules selectively involved in the
      interaction.

PMID- 21870256
TI  - Noncovalent pADPr interaction with proteins and competition with RNA for binding
      to proteins.
AB  - PARP1 can modify a variety of proteins through conserved domains in noncovalent
      manner. Since poly(ADP-ribose) is highly negatively charged and has a strong
      binding affinity for its target proteins, noncovalent binding by poly(ADP-ribose)
      modulates the protein activity during developmental processes. In this section,
      the methods including co-immunoprecipitation and dot-blot assay were illustrated
      for determining the specific interaction between poly(ADP-ribose) and proteins.
      Furthermore, the protocol for RNA EMSA was described to determine whether pADPr
      binding to hnRNPs can inhibit RNA-binding ability of human hnRNP A1.

PMID- 21870257
TI  - Affinity-based assays for the identification and quantitative evaluation of
      noncovalent poly(ADP-ribose)-binding proteins.
AB  - Poly(ADP-ribose) polymerases have been linked to several cellular functions, most
      of which being mediated through the dynamics of poly(ADP-ribose) (pADPr). In
      several pathways, pADPr is the effector molecule that regulates cellular
      signaling and dictates biological outcomes. pAPDr is a central molecule that is
      capable of promoting both cell survival through the maintenance of genome
      integrity and cell death that occurs by way of a signal-mediated apoptotic-like
      process. Thus, interactions with pADPr are extremely important in bringing about
      the balanced regulation that controls cell fate. Further clues regarding these
      functions are emerging from a growing list of proteins with which pADPr
      interacts. Here, we describe the current approaches for investigating noncovalent
      protein interactions with pADPr.

PMID- 21870258
TI  - Detecting and quantifying pADPr in vivo.
AB  - Poly(ADP-ribose) polymerases (PARP) participate in diverse biological processes
      contributing to cellular homeostasis or exacerbating injury. PARP catalyzes the
      addition of ADP-ribose molecules (pADPr) to the target proteins, a process termed
      poly-ADP-ribosylation. Overactivation of PARP, as reflected by increased poly-ADP
      ribosylation, accumulation of pADPr-modified proteins or free pADPr, contributes
      to the depletion of NAD(+) and mitochondrial dysfunction, potentially leading to
      cell death via apoptosis or necrosis. Since PARP over-activation has been
      identified as a key contributor to the pathobiology of many diseases, monitoring
      PARP 1 activation by detecting and quantifying pADPr may provide valuable
      mechanistic insights as well as facilitating therapeutic drug monitoring for PARP
      inhibitors.Several non-isotopic immunodetection methods for quantifying pADPr are
      discussed: western blotting of poly-ADP-ribosylated proteins, cellular
      localization of pADPr by immunohistochemistry, quantification of pADPr by enzyme
      linked immunoassay and small-scale two-dimensional gel electrophoresis.

PMID- 21870259
TI  - Purification of recombinant poly(ADP-ribose) polymerases.
AB  - The purification of Poly(ADP-ribose) polymerases from overexpressing cells (Sf9
      insect cells, Escherichia coli) has been updated to a fast and reproducible three
      chromatographic steps protocol. After cell lysis, proteins from the crude extract
      are separated on a Heparine SepharoseTM column. The PARP-containing fractions are
      then affinity purified on a 3-aminobenzamide SepharoseTM chromatographic step.
      The last contaminants and the 3-methoxybenzamide used to elute the PARP from the
      previous affinity column are removed on the high-performance strong cations
      exchanger SourceTM 15S matrix. The columns connected to an AKTATM purifier system
      allow the purification of PARPs in 3 days with a high-yield recovery. As
      described in the protocol, more than 11 mg of pure and highly active mouse PARP-2
      can be obtained from 1 L of Sf9 insect cell culture.

PMID- 21870260
TI  - Methods for purification of proteins associated with cellular poly(ADP-ribose)
      and PARP-specific poly(ADP-ribose).
AB  - Poly(ADP-ribose) (pADPr) is a posttranslational modification that regulates
      protein function through two major mechanisms: covalent modification of acceptor
      proteins and noncovalent binding of proteins to pADPr. pADPr is synthesized by a
      family of enzymes called poly(ADP-ribose) polymerases (PARPs) that are themselves
      major targets of pADPr modification. Here, we outline two methods for the
      purification of pADPr-binding proteins via pADPr purification under native
      conditions: purification of cellular pADPr and pADPr covalently linked to
      specific PARPs. Together, these methods provide complementary approaches to the
      identification of noncovalent pADPr-protein interactions in the cell.

PMID- 21870261
TI  - Purification and characterization of poly(ADP-ribosyl)ated DNA replication/repair
      complexes.
AB  - PARP-1, the best studied isoform and most abundantly expressed member of the PARP
      family of 18 proteins, catalyzes the poly(ADP-ribosyl)ation (PARylation) of
      various nuclear proteins and play key roles in DNA repair, genome maintenance,
      DNA replication, recombination, apoptosis, gene expression, and regulation of
      chromatin function. PARylation modulates the functions of target proteins, mainly
      PARP-1 itself. A multifunctional enzyme, PARP-1 has been localized within DNA
      replication, repair, recombination, and transcription complexes, and modifies and
      regulates the functions of specific components of these complexes. PARylation can
      regulate the activities of replicative enzymes, such as DNA polymerases alpha,
      delta, and epsilon, topo I and II, primase, RPA, and PCNA in isolated enzymes or
      within DNA replication complexes (DNA synthesome). PARP-1 and PARylation may (1)
      play dual roles in nuclear processes, depending on the levels of the substrate
      NAD and the presence of PARP-activating DNA breaks, (2) recruit acceptor proteins
      to certain sites or complexes through direct association or through binding to
      PAR and PAR-binding proteins, and (3) alters the nucleosomal structure of DNA by
      PARylation of nucleosomal proteins, such as histone H1 to destabilize higher
      order chromatin structures and promote access of DNA repair and replication
      enzymes as well as transcription factors to these sites. Here, we describe
      biochemical approaches that have been utilized in our laboratory for the
      purification and characterization of PARylated DNA replicative complexes. These
      methods can be modified for the purification of complexes involved in other
      nuclear processes. This chapter also briefly discusses current methods by which
      new PARylated complexes are being identified and studied. Identification,
      evaluation, and characterization of new complexes could aid in the elucidation of
      the molecular mechanisms by which PARylation and PARP mediates its pleiotropic
      roles in various nuclear processes.

PMID- 21870263
TI  - Purification of human PARP-1 and PARP-1 domains from Escherichia coli for
      structural and biochemical analysis.
AB  - A general method to express and purify full-length human poly(ADP-ribose)
      polymerase-1 (PARP-1), individual PARP-1 domains, and groups of PARP-1 domains
      from Escherichia coli cells is described. The procedure allows for robust
      production of highly pure PARP-1 that is free of DNA contamination and well
      suited for biochemical experiments and for structural and biophysical analysis.
      Two biochemical assays for monitoring PARP-1 automodification activity are
      presented that can be used to evaluate purified PARP-1, combinations of PARP-1
      domains, or PARP-1 mutants.

PMID- 21870262
TI  - PARP1 genomics: chromatin immunoprecipitation approach using anti-PARP1 antibody
      (ChIP and ChIP-seq).
AB  - Poly(ADP-ribose) polymerase1 (PARP1) is a global regulator of different cellular
      mechanisms, ranging from DNA damage repair to control of gene expression. Since
      PARP1 protein and pADPr have been shown to persist in chromatin through cell
      cycle, they may both act as epigenetic markers. However, it is not known how many
      loci are occupied by PARP1 protein during mitosis genome-wide. To reveal the
      genome-wide PARP1 binding sites, we used the ChIP-seq approach, an emerging
      technique to study genome-wide PARP1 protein interaction with chromatin. Here, we
      describe how to perform ChIP-seq in the context of PARP1 binding sites
      identification in chromatin, using human embryonic kidney cell lines.

PMID- 21870264
TI  - Regulation of chromatin structure by PARP-1.
AB  - PARP-1 is the most abundantly expressed member of a family of proteins that
      catalyze the transfer of ADP-ribose units from NAD(+) to target proteins.
      Numerous studies on PARP-1 have revealed its critical roles in regulating various
      molecular and cellular processes including DNA damage detection and repair,
      chromatin modification.In this chapter, we describe various in vitro methods to
      investigate the function of PARP-1 in the regulation of chromatin structure using
      chromatin templates.

PMID- 21870265
TI  - The use of PARP inhibitors in cancer therapy: use as adjuvant with chemotherapy
      or radiotherapy; use as a single agent in susceptible patients; techniques used
      to identify susceptible patients.
AB  - This chapter describes some of the techniques in use in our laboratories for the
      investigation of PARP inhibitors in clinical medicine. More specifically, we are
      involved in investigating the utility of PARP inhibitors in the treatment of
      hematopoietic malignancies. We are also actively investigating the properties of
      the PARP systems in cell biology. We begin the chapter with a very brief history
      of the invention and use of PARP inhibitors. We then explain the underlying logic
      of the use of PARP inhibitors either in combination with chemo- or radiotherapy
      or as single agents used alone. We then provide in full detail the protocols that
      we use to study PARP inhibitors in cell biology to identify patients that should
      be susceptible to PARP inhibitor treatment and to manage and investigate these
      patients throughout their treatment.

PMID- 21870266
TI  - Quantification of PARP activity in human tissues: ex vivo assays in blood cells
      and immunohistochemistry in human biopsies.
AB  - Poly (ADP-ribosyl)ation of proteins is a posttranslational modification mediated
      by poly (ADP-ribose) polymerases (PARPs) that uses NAD(+) as substrate to form
      the negatively charged polymer of poly (ADP-ribose) (PAR). After DNA damage, PARP
      1 is responsible for approximately 90% of the total cellular PARylation activity.
      Numerous studies showed activation of PARP-1 in various conditions associated
      with oxidative and nitrosative stress, such as ischemia-reperfusion injury,
      diabetes mellitus, and inflammation, and also proved the beneficial effects of
      PARP inhibitors. Pharmacological inhibitors of PARP move toward clinical testing
      for a variety of indications, including cardioprotection and malignant tumors.
      Some of the compounds are already in clinical trials. These advances necessitate
      the detection of PARP activation in human tissues. In the present chapter, we
      review specific methods used to detect PARP activation in human circulating
      leukocytes and human tissue sections.

PMID- 21870268
TI  - Generation of poly(ADP-ribosyl)ation deficient mutants of the transcription
      factor, CTCF.
AB  - Generation of the mutated versions of proteins deficient for poly(ADP
      ribosyl)ation (PARylation) is a major challenge because there is no clearly
      defined consensus site for PARylation. In this chapter, we describe possible
      strategies to produce such mutants, demonstrated by the example of CTCF, a
      transcription factor. To achieve this in our study, the protein domain modified
      by PARylation was mapped and the amino acids, which can be potentially PARylated,
      selected. Mutations of such individual amino acids as either single or
      combinatorial mutations were introduced by site-directed mutagenesis, using
      mutagenic primers and the wild-type sequences as a template. Mutants were
      validated by DNA sequencing and assessed for the presence of the PARylation mark.
      The latter was achieved by ectopic expression of mutated proteins in cells,
      followed by immunoprecipitation with the polyclonal anti-PAR antibody and Western
      analysis with a protein-specific antibody. The PARylation-deficient CTCF mutant
      was identified and compared with the wild-type protein. Based on several general
      characteristics (nuclear distribution/localisation, stability and levels of
      expression in the cell), the PARylation-deficient mutant was comparable with the
      wild-type CTCF.

PMID- 21870267
TI  - Assays for hypermethylation of the BRCA1 gene promoter in tumor cells to predict
      sensitivity to PARP-inhibitor therapy.
AB  - The breast cancer 1 and 2, early onset (BRCA1 and BRCA2) genes are important for
      double-strand break repair by homologous recombination. Cells with inactivating
      mutations of the BRCA1 or BRCA2 tumor suppressor genes show increased sensitivity
      to Poly-ADP ribose polymerase (PARP)-inhibitors in vitro. Sporadic breast tumors
      with BRCA1 promoter hypermethylation show a similar phenotype to familial BRCA1
      patient tumors termed "BRCAness." Sporadic ovarian tumors with functional
      inactivation of BRCA1 by hypermethylation will also have the BRCA-deficiency
      phenocopy. The loss of BRCA1 expression associated with promoter hypermethylation
      will disrupt BRCA-associated DNA repair and may sensitize tumors to BRCA-directed
      therapies. Thus, the determination of methylation status of BRCA1 may be an
      important predictive classifier of response to PARP-inhibitor therapy. The
      methylation, and thereby functional, status of other genes implicated in the
      wider BRCA/homologous recombination (HR) pathway may also be relevant to the
      prediction of response to PARP-inhibitor therapy. Here, we describe the four
      optimal technologies for assaying the promoter methylation status of BRCA1 and/or
      other genes.

PMID- 21870269
TI  - Phenotypic characterization of Parp-1 and Parp-2 deficient mice and cells.
AB  - Poly(ADP-ribosyl)ation is a post-translational modification of proteins mediated
      by Poly(ADP-ribose) polymerases (Parps), a family of 17 members. Among them,
      Poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 are so far the sole enzymes
      whose catalytic activity has been shown to be induced by DNA strand breaks. The
      generation and characterization of Parp-1 and Parp-2 deficient cellular and
      animal models have largely contributed to describe both proteins as active
      players of the base excision repair/single-strand break repair (BER/SSBR) process
      with both redundant and more specific functions. Double Parp-1(-/-)Parp-2(-/-)
      embryos die at gastrulation demonstrating the crucial role of poly(ADP
      ribosyl)ation during embryonic development, whereas a specific female lethality
      related to X chromosome instability is associated with the Parp-1(+/-)Parp-2(-/-)
      genotype. Finally, recent research discovered emerging unique functions of Parp-2
      in physiological processes including spermatogenesis, T-cell maturation, and
      adipogenesis although with distinct mechanisms. In this chapter, we describe
      standard operating procedures used to genotype and phenotype both mouse lines and
      the derived mouse embryonic fibroblasts.

PMID- 21870270
TI  - Poly(ADP-ribosyl)ation pathways in mammals: the advantage of murine PARG null
      mutation.
AB  - Studies suggest that inhibiting the hydrolysis of poly(ADP-ribose) (PAR) by
      targeting the enzyme PAR glycohydrolase (PARG) is a potential chemotherapeutic
      strategy to induce cell death. However, the lack of structural data for PARG has
      hindered the discovery of specific PARG inhibitors and thus hampered the search
      for cellular effects dependent on the hydrolysis of PAR. We previously generated
      a murine PARG null cell model to identify the intracellular processes mediated by
      PARG. Using this system, the only mammalian system to date that completely lacks
      PARG activity, we have shown that the absence of PARG leads to massive amounts of
      cell death due to increased levels of PAR. Further, we have shown that PARG null
      TS cells exhibit profound hypersensitivity to low doses of DNA-damaging agents.
      This hypersensitivity most likely results from the high levels of DNA damage that
      occur after treatment of these cells with nonlethal doses of DNA-damaging agents.

PMID- 21870271
TI  - Genetic approaches to targeting multiple PARP genes in a mammalian genome.
AB  - The aim of this chapter is to present feasible strategies for producing novel
      Parp knock out mice as well multiple knock outs utilizing genetrap and
      specifically gene targeted ES cell clones publically available through
      international programs such as KOMP and IGTC. Specifically, we first describe
      general considerations and strategic decisions that precede the generation of
      knock out mice using these available materials, and an overview over clones
      relevant to the PARP family is provided. Detailed protocols for splice variant
      analysis of the gene of interest, to determine what to expect from a given gene
      trap clone, are presented. Furthermore, we provide a detailed and widely
      applicable step by step method to fine-map genomic genetrap insertion sites once
      targeted clones have been obtained. This is a prerequisite for development of
      feasible genotyping methods that usually have to be developed by the user.

PMID- 21870272
TI  - Approaches to separate and identify polyADP-ribosylated proteins using poly(ADP
      ribose) glycohydrolase-knockout Drosophila.
AB  - PolyADP-ribosylation plays an essential function in maintenance of genomic
      stability and cell survival. Although there are several proteins served as
      acceptor proteins in vitro, there are few proteins in vivo that are identified,
      including poly(ADP-ribose) polymerase-1. We have been studying to analyze the
      mechanism of neuronal cell death observed in poly(ADP-ribose) glycohydrolase
      (PARG)-knockout Drosophila melanogaster that shows accumulation of polyADP
      ribosylated proteins in the brain. As the first step, we have been trying to
      isolate the polyADP-ribosylated accepter proteins from the PARG-knockout fly. The
      strategy is to extract the polyADP-ribosylated proteins and isolate them with
      affinity chromatography using monoclonal antibody against poly(ADP-ribose) (PAR)
      (10H). The bound fraction was eluted by buffer containing salt. Next, part of
      eluted fraction is treated with NaOH for separating the proteins from PAR chain.
      Nontreated fraction and treated fraction were separated with two-dimensional gel
      electrophoresis. After protein staining, the specific spots that were newly found
      after NaOH treatment were candidate acceptor proteins for polyADP-ribosylation in
      vivo and could be analyzed with liquid chromatography-mass spectrometry. We
      present the procedure to this approach.

PMID- 21870273
TI  - Immunolocalization of poly ADP-ribose on Drosophila polytene chromosomes.
AB  - Poly ADP-ribosylation (PARylation) is a posttranslational protein modification
      catalyzed by poly -ADP-ribose polymerases (PARPs). Poly ADP-ribose metabolism is
      involved in a wide range of biological processes, such as maintenance of genome
      stability, transcriptional regulation, energy metabolism, and programed cell
      death. Recently, chromatin components, including histones, have been shown to be
      targets of PARylation. Unlike mammals, which have several PARP-encoded genes, the
      model organism Drosophila melanogaster has only one PARP gene, highly related to
      mammalian PARP1. These features make flies a great model system to study PARP
      biology. Commercially available antibodies recognizing this covalent modification
      have made possible the development of immunofluorescence approaches to study
      PARylation of chromatin components. Here, we present a protocol to immunostain
      polytene chromosomes of the model system D. melanogaster.

PMID- 21870274
TI  - The immunodetection of pADPr in Drosophila tissues: immunostaining of thick
      sections; immuno-EM.
AB  - Poly(ADP)ribose (pADPr) modification is known to regulate the state of DNA
      condensation in the cell nucleus. Under normal conditions, pADPr is extremely
      unstable due to the enzymatic activity of pADPr glycohydrolase (PARG). We studied
      the salivary glands of PARG-deficient Drosophila larvae at both the fluorescence
      and electron microscope levels by immunolabeling of pADPr on cryosections. This
      approach proved very successful in preserving the antigenicity of pADPr as well
      as other antigens. pADPr concentrates in areas intercalating to heterochromatin
      as well as two types of nuclear granules that were subsequently shown to
      represent ectopic Cajal bodies.

PMID- 21870275
TI  - Poly(ADP-ribose) metabolism analysis in the nematode Caenorhabditis elegans.
AB  - Poly(ADP-ribose) polymerases (PARPs) are a well-conserved family of enzymes found
      in many species. These enzymes catalyze poly(ADP-ribosyl)ation, a modification of
      proteins implicated in a variety of nuclear processes, such as DNA damage
      signaling and repair, cell death and survival, and transcription. Poly(ADP
      ribose) glycohydrolase (PARG) is responsible for the specific hydrolysis of
      poly(ADP-ribose) (PAR), the product of poly(ADP-ribosyl)ation, and its action is
      required for the modified proteins to regain their original function in the cell.
      The metabolism of PAR can be studied in the nematode Caenorhabditis elegans as
      genes encoding PARP and PARG enzymes have been identified and characterized in
      its genome. We have shown the capacity of these PARPs to produce PAR as well as
      the capacity of the nematode to catabolize PAR into ADP-ribose units through the
      enzymatic activity of its PARGs. Therefore, C. elegans is a novel model to study
      PAR metabolism in eukaryotes that offers new avenues to investigate the role(s)
      of poly(ADP-ribosyl)ation in development as well as DNA repair, programmed cell
      death, and aging.

PMID- 21870276
TI  - Genetic dissection of PARylation in the filamentous fungus Neurospora crassa.
AB  - PARylation is a posttranslational protein modification carried out by PAR
      polymerases (PARPs). These enzymes function as ADP-ribose transferases that add
      polymers of ADP-ribose (PAR) to target proteins. PARP proteins have critical
      functions impacting the aspects of normal human health, such as aging, as well as
      disease development, particularly cancer. Recently, the powerful antitumor PARP
      inhibitor Olaparib was shown to be effective in blocking the progression of
      BRCA1/2-associated tumors, prompting Bruce Alberts to call for an expansion of
      cancer research beyond utilization of cancer cell lines to include model
      organisms, such as bacteria, yeast, worms, flies, and mice. Although Dr. Alberts
      did not specifically mention the filamentous fungus Neurospora crassa, it is now
      known that Neurospora is the only genetically tractable model eukaryote with
      completely dispensable PARylation. PARylation in Neurospora can be entirely
      eliminated by disruption of a single predicted ORF, encoding a nuclear localized
      PARP protein termed Neurospora PARP ortholog (NPO). We, thus, present this
      initial genetic characterization of PARylation in N. crassa as evidence of the
      supreme advantage of using Neurospora as a tool for the genetic dissection of
      PARP and PARylation and emphasize the power of this system to advance
      unparalleled contributions to knowledge in this field.

PMID- 21870277
TI  - Purification of the poly-ADP-ribose polymerase-like thermozyme from the archaeon
      Sulfolobus solfataricus.
AB  - Several different protocols have been developed to purify the ADP-ribosylating
      enzyme from Sulfolobus solfataricus. A number of techniques have been applied in
      regard to the crude homogenate preparation and protein extraction. Either
      mechanical cell lysis with DNAase digestion or freeze-thawing with sonication
      allowed to obtain fairly similar amounts of the thermozyme in the homogenate.
      While similar recovery of thermozyme was obtained by employing both purification
      protocols, the proteins were solubilized with different methods, and the affinity
      chromatography on NAD-Agarose of the first protocol was replaced by a gel
      filtration step in the second protocol. When enzyme activity was compared with
      electrophoresis and anti-poly-ADP-ribose polymerase 1 antibody immunoblotting
      results, it was noticed that lysis by sonication induces aggregation of monomeric
      PARP-like thermozyme at least in a dimeric form. The dimeric aggregate is also
      evidenced by treatment of cells with sonication followed by different protein
      extraction (Method III). Finally, we describe the third purification protocol
      that allows fast recovery of small amounts of purified ADP-ribosylating enzyme.

PMID- 21870278
TI  - Strategies employed for the development of PARP inhibitors.
AB  - This chapter describes the approaches taken in the development of the first PARP
      inhibitor to enter into clinical trial, AG-014699. We describe the general
      principles of crystal-based drug design, the purification, and crystallization of
      the PARP-1 catalytic domain, and how this approach was used to develop highly
      potent PARP inhibitors based on the nicotinamide pharmacophore. Several methods
      have been used to determine the inhibitory potency of designed inhibitors in cell
      free and whole cell assays; each is described with reference to its advantages
      and disadvantages.

PMID- 21870279
TI  - Small-molecule collection and high-throughput colorimetric assay to identify
      PARP1 inhibitors.
AB  - During the last few years, poly(ADP-ribose)polymerase (PARP) proteins became a
      very popular target for anticancer treatment. Many PARP inhibitors have been
      generated and tested by pharmacological industry. However, most of them were
      designed to disrupt the DNA-dependent PARP1 protein activation pathway and were
      based on a competition with NAD for a binding site on PARP molecule and,
      therefore, on disruption of PARP-mediated enzymatic reaction. This limitation
      resulted in a discovery of mainly nucleotide-like PARP1 inhibitors which may
      target not only PARP, but also other pathways involving NAD and other
      nucleotides. Here, we describe a strategy for the identification of PARP
      inhibitors that target a different pathway, the histone H4-dependent PARP1
      activation. Besides the identification of NAD competitors in a small-molecule
      collection, this approach allows finding novel classes of PARP inhibitors that
      specifically disrupt H4-based PARP activation.

PMID- 21870280
TI  - Studying G2 DNA damage checkpoints using the fission yeast Schizosaccharomyces
      pombe.
AB  - Using synchronized cells, one can directly measure delay in mitosis brought about
      by the G2 DNA damage checkpoint in response to exposure to exogenous DNA damaging
      agents. Scoring mitosis in the fission yeast Schizosaccharomyces pombe is
      relatively simple. Many techniques exist for synchronizing cells for such assays.
      We present a detailed explanation of the setup and use of centrifugal elutriation
      to synchronize cells in G2, exposure of cells to DNA damage, and measurement of
      mitotic progression and delay.

PMID- 21870281
TI  - Studying S-phase DNA damage checkpoints using the fission yeast
      Schizosaccharomyces pombe.
AB  - Slowing of replication in response to DNA damage is a universal response to DNA
      damage during S-phase. Originally discovered to be defective in checkpoint mutant
      cells in metazoans, this S-phase DNA damage checkpoint response has been
      extensively studied in yeast. Unlike other checkpoints that completely arrest
      cell cycle, the S-phase DNA damage checkpoint slows but does not completely halt
      replication in response to DNA damage. An analysis of mutants defective in the
      slowing response requires a sensitive assay to measure this quantitative effect.
      The use of centrifugal elutriation to synchronize cells and improved techniques
      in preparing cells for flow cytometry allow for more sensitive and accurate
      measurement of cells' ability to slow replication in the presence of DNA damage.
      This chapter describes the use of transient cdc10-M17 temperature sensitive
      allele arrest and release combined with centrifugal elutriation to synchronize
      cells in G1. The S-phase progression of these cells is then assayed by flow
      cytometry of isolated nuclei, which allows sensitive determination of replication
      kinetics.

PMID- 21870282
TI  - Methods for studying the G2 DNA damage checkpoint in mammalian cells.
AB  - In response to post-replicative DNA damage, cells activate the G2 DNA damage
      checkpoint to ensure mitosis is not attempted until the damage has been repaired.
      This is a common response to a variety of DNA damaging agents, including ionizing
      radiation and many chemotherapeutic agents used in the treatment of cancer. The
      G2 DNA damage checkpoint acts to inhibit the mitotic cyclin-dependent kinase, and
      thus cells are arrested in the G2 phase of the cell cycle. The kinetics of this
      checkpoint can be assayed by staining cells for markers of mitosis, which can
      then be quantified by flow cytometry or microscopy.

PMID- 21870283
TI  - Evaluating spindle assembly checkpoint competence in mouse oocytes using
      immunoblotting.
AB  - The spindle assembly checkpoint (SAC) is a quality control mechanism for
      overseeing the fidelity of chromosome segregation. By modulating the activity of
      the anaphase-promoting complex or cyclosome (APC/C), the SAC sets the timing of
      anaphase-onset by co-ordinating the timely destruction of key proteins with the
      completion of chromosome alignment. How mammalian oocytes regulate chromosome
      segregation during the first meiotic division (meiosis I) is of immense
      importance as mis-segregation at this crucial stage in human oocytes underpins
      the majority of human aneuploidy and birth defects. In recent years, the SAC has
      been shown to be indispensable for the accuracy of meiosis I chromosome
      segregation. Here, I describe a technique based on immunoblotting for evaluating
      SAC competence during meiosis I in mouse oocytes.

PMID- 21870284
TI  - Analysis of changes in protein level and subcellular localization during cell
      cycle progression using the budding yeast Saccharomyces cerevisiae.
AB  - Methods are described here to monitor changes in protein level and subcellular
      localization during the cell cycle progression in the budding yeast Saccharomyces
      cerevisiae. Cell synchronization is achieved by an alpha-factor-mediated block
      and-release protocol. Cells are collected at different time points for the first
      two cell cycles upon release. Cellular DNA contents are analyzed by flow
      cytometry. Trichloroacetic acid protein precipitates are prepared for monitoring
      levels of cell cycle regulated proteins by Western blotting. The dynamic changes
      in protein subcellular localization patterns are examined by indirect
      immunofluorescence microscopy.

PMID- 21870285
TI  - Studying cell cycle checkpoints using Drosophila cultured cells.
AB  - Drosophila cell lines are valuable tools to study a number of cellular processes,
      including DNA damage responses and cell cycle checkpoint control. Using an in
      vitro system instead of a whole organism has two main advantages: it saves time
      and simple and effective molecular techniques are available. It has been shown
      that Drosophila cells, similarly to mammalian cells, display cell cycle
      checkpoint pathways required to survive DNA damaging events (de Vries et al.
      2005, Journal of Cell Science 118, 1833-1842; Bae et al. 1995, Experimental Cell
      Research 217, 541-545). Moreover, a number of proteins involved in checkpoint and
      cell cycle control in mammals are highly conserved among different species,
      including Drosophila (de Vries et al. 2005, Journal of Cell Science 118, 1833
      1842; Bae et al. 1995, Experimental Cell Research 217, 541-545; LaRocque et al.
      2007, Genetics 175, 1023-1033; Sibon et al. 1999, Current Biology 9, 302-312;
      Purdy et al. 2005, Journal of Cell Science 118, 3305-3315). Because of
      straightforward and highly efficient methods to downregulate specific transcripts
      in Drosophila cells, these cells are an excellent system for genome-wide RNA
      interference (RNAi) screens. Thus, the following methods, assays and techniques:
      Drosophila cell culture, RNAi, introducing DNA damaging events, determination of
      cell cycle arrest, and determination of cell cycle distributions described here
      may well be applied to identifying new players in checkpoint mechanisms and will
      be helpful to investigate the function of these new players in detail. Results
      obtained with studies using in vitro systems can subsequently be extended to
      studies in the complete organism as described in the chapters provided by the Su
      laboratory and the Takada laboratory.

PMID- 21870286
TI  - In vivo live-analysis of cell cycle checkpoints in Drosophila early embryos.
AB  - Live-imaging of cells has been an excellent technique to provide us with highly
      accurate and valuable information about cell cycle checkpoint regulation and DNA
      damage responses. Early stage Drosophila embryos have several advantages to be
      studied by live-imaging. Fly embryos are much tougher than cultured cells and
      stand up to relatively rough manipulation, such as protein/chemical
      microinjection followed by time-lapse imaging. Cell cycles in the embryonic
      cleavage stage progress rapidly (9-20 min/cycle) and nuclear divisions are
      synchronous, allowing observation of multiple nuclei/cell cycles in a short
      period of time. Somatic precursor nuclei form a monolayer at the cortex of the
      embryo during the syncytial blastoderm stage (cell cycles 10-13). Thus the nuclei
      in this stage are particularly accessible by various microscopic techniques
      (Sullivan and Theurkauf, 1995, Curr. Opin. Cell Biol. 7, 18-22). Live-imaging of
      embryos complements the versatility of the Drosophila embryonic system, in which
      we can utilize various approaches, including genetics and biochemistry, to obtain
      comprehensive understanding of biological processes. In this chapter, we will
      describe basic methods of microinjection and live-imaging during early
      embryogenesis by differential interference contrast (DIC) or confocal microscopy,
      and the use of such methods to study cell cycle checkpoints.

PMID- 21870287
TI  - Using Drosophila larval imaginal discs to study low-dose radiation-induced cell
      cycle arrest.
AB  - Under genotoxic stress, activation of cell cycle checkpoint responses leads to
      cell cycle arrest, which allows cells to repair DNA damage before continuing to
      cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent
      in vivo model system for studying radiation-induced cell cycle arrest. Larval
      imaginal discs go into cell cycle arrest after being subjected to low-dose
      irradiation, are subject to easy genetic manipulation, are not crucial for
      survival of the organism, and can be dissected easily for further molecular or
      cellular analysis. In this chapter, we describe methods for assessing low-dose
      irradiation-induced cell cycle arrest. Mitotic cells are identified by
      immunofluorescence staining for the mitotic marker phosphorylated histone H3
      (phospho-histone H3 or pH3). When wandering third-instar control larvae, without
      transgene expression, are exposed to 500 rads of X-ray or gamma-ray irradiation,
      the number of pH3-positive cells in wing imaginal discs is reduced from hundreds
      before irradiation to approximately 30 after irradiation, with an equal
      distribution between the anterior and posterior compartments (Yan et al., 2011,
      FASEB J). Using the GAL4/UAS system, RNAi, cDNA, or microRNA sponge transgenes
      can be expressed in the posterior compartment of the wing disc using drivers such
      as engrailed (en)-Gal4, while the anterior compartment serves as an internal
      control. This approach makes it possible to do genome-wide genetic screening for
      molecules involved in radiation-induced cell cycle arrest.

PMID- 21870288
TI  - Screening for radiation sensitizers of Drosophila checkpoint mutants.
AB  - Anti-cancer therapy is largely comprised of radiation, surgery, and chemotherapy
      treatments. Although a single mode of therapy can be effective in treating
      certain types of cancer, none presents a cure. Multi-modal therapy, the use of
      two or more agents in combination (e.g., radiation and chemotherapy together),
      shows potential for a more effective treatment of cancer. The challenge then is
      identifying effective therapy combinations. In this chapter, we describe the use
      of Drosophila as a whole animal in vivo model to screen for small molecules that
      effectively combine with ionizing radiation to kill checkpoint mutants
      preferentially over wild-type. The differential use of wild-type and checkpoint
      mutants has the potential to identify molecules that act in a genotype-specific
      manner to eradicate checkpoint mutant tissues when combined with radiation, while
      sparing wild-type tissues.

PMID- 21870289
TI  - Study of cell cycle checkpoints using Xenopus cell-free extracts.
AB  - Cell cycle checkpoints are involved in the coordinated response to DNA damage and
      thus play a key role in maintaining genome integrity. Several model systems have
      been developed to study the mechanisms and complexity of checkpoint function.
      Here we describe the application of cell-free extracts derived from Xenopus eggs
      as a model system to investigate DNA replication, damage, and checkpoint
      activation. We outline the preparation of cell-free extracts, DNA substrates and
      their subsequent use in assays aimed at understanding cell cycle checkpoints, and
      related processes. Several advances made over the years have enabled the
      continued use of the Xenopus system to answer a variety of questions in DNA
      replication, repair and checkpoint signaling. It is anticipated that the
      versatile Xenopus system is amenable to future modification as well to continue
      studies attempting to understand these important physiological processes.

PMID- 21870290
TI  - Analyzing DNA replication dynamics of genotoxin-treated cells using velocity
      sedimentation.
AB  - Following acquisition of DNA damage S-phase progression may potentially be
      affected via multiple mechanisms. For example DNA damage-activated signal
      transduction pathways negatively regulate the initiation of DNA synthesis at
      unfired origins of replication, a process termed the 'S-phase checkpoint' or the
      'intra-S-phase checkpoint'. Additionally, many DNA lesions pose physical barriers
      to replication forks and therefore inhibit DNA synthesis directly by blocking the
      elongation of active replicons. Inhibition of DNA synthesis in response to DNA
      damage is commonly assayed by measuring incorporation of radiolabeled or
      halogenated nucleotides into bulk genomic DNA. However, these techniques do not
      distinguish between effects of DNA damage on initiation and elongation phases of
      DNA synthesis. The velocity sedimentation protocol described here allows
      investigators to determine the effects of DNA damage on initiation and elongation
      events. This technique involves labeling replicating DNA with (3)H-thymidine,
      then analyzing the size distribution of labeled ssDNAs based on their
      differential density sedimentation profiles after centrifugation through alkaline
      sucrose gradients. Determining the relative abundance and growth rates of small
      nascent ssDNAs provides an index of initiation and elongation events,
      respectively. Therefore, analysis of replication dynamics using velocity
      sedimentation provides a potentially valuable tool for assaying S-phase
      checkpoints as well as other aspects of DNA replication.

PMID- 21870291
TI  - Methods for studying checkpoint kinases - Chk1.
AB  - Attempts to passage through mitosis with unrepaired DNA damage or incompletely
      replicated DNA leads to genome instability and/or cell death. To prevent this
      from occurring, an ancient checkpoint (known as the G2 DNA damage checkpoint)
      that inhibits the activation of the mitotic cyclin-dependent kinase is activated
      to hold cells in the G2 phase of the cell cycle. The effector of this checkpoint
      is Chk1, a protein serine-threonine kinase. Chk1 contains an N-terminal catalytic
      domain, and C-terminal regulatory domain. Within the regulatory domain there are
      two residues, Serine-317 (S317) and Serine-345 (S345), which are phosphorylated
      in active Chk1 molecules, and subsequently dephosphorylated to inactivate Chk1
      and allow mitotic entry. Phospho-specific antibodies can be used to detect these
      activating phosphorylations, and this provides a simple and sensitive marker of
      Chk1 activation.

PMID- 21870292
TI  - A human cell extract-based assay for the activation of ATM and ATR checkpoint
      kinases.
AB  - The Ataxia telangiectasia-mutated (ATM) and the ATM-Rad3-related (ATR) kinases
      are master regulators of the DNA damage-signaling pathways that respond to a wide
      variety of DNA damage. In this chapter, we describe an in vitro biochemical assay
      to study the activation of ATM and ATR by double-stranded DNA breaks (DSBs)
      (Shiotani and Zou, 2009, Mol Cell 33, 547-58). In this assay, DNA fragments with
      different structural features are used to activate ATM and ATR in human cell
      extracts, and the activation of ATM and ATR is monitored by the phosphorylation
      of specific ATM and ATR substrates. Importantly, in this assay both ATM and ATR
      are activated in a DNA structure-regulated manner, providing a useful tool to
      characterize the DNA structural determinants for their activation. The four
      primary steps of this assay are as follows: (1) preparation of nuclear extracts
      from cultured human cells; (2) generation of various DNA fragments using DNA
      oligonucleotides or plasmids; (3) incubation of DNA fragments in extracts; (4)
      analysis of the phosphorylation of specific ATM or ATR substrates.

PMID- 21870293
TI  - Analyzing p53 regulated DNA damage checkpoints by flow cytometry.
AB  - The most critical feature of the cellular response to DNA damage is the ability
      of the cell to pause and repair the damage so that detrimental mutations will not
      be passed along to future generations of cells. The cell cycle of mammalian cells
      is equipped with checkpoints that can prevent cell cycle progression. Cells can
      either be arrested before replication of the DNA when the cells have a 2 N amount
      of DNA or after replication and prior to cell mitosis when the cells have a 4 N
      amount of DNA. Flow cytometry is a standard technique that is used to 'sort'
      cells based on their DNA content. It uses the principles of light scattering,
      light excitation, and emission of fluorochrome molecules to generate data about
      individual cells. The cells are fixed and permeabilized so that the DNA can be
      stained with a fluorescent dye. Cells that have a 2 N amount of DNA can be
      separated from cells with a 4 N amount of DNA. Using this technique, changes in
      the profile of the G1, S, and G2/M phases of the cell cycle are readily seen
      after DNA damage.

PMID- 21870294
TI  - Using Drosophila S2 cells to measure S phase-coupled protein destruction via flow
      cytometry.
AB  - Cell proliferation depends on the timely synthesis and destruction of proteins at
      specific phases of the cell cycle. Recently it was discovered that the
      destruction of several key cell cycle regulatory proteins during S phase is
      coupled directly to DNA replication. These proteins harbor a motif called a PIP
      degron that mediates binding to chromatin bound PCNA at replication forks and
      recruits the CRL4(Cdt2) E3 ubiquitin ligase. These interactions comprise an
      elegant mechanism for coupling DNA replication with ubiquitylation and subsequent
      proteolysis by the 26S proteasome. Here we describe a flow cytometry-based method
      using Drosophila S2 cells that recapitulates S phase-specific protein
      proteolysis. Because of the high degree of evolutionary conservation of the PIP
      degron and CRL4(Cdt2) and the ease of culturing and inhibiting gene function by
      RNAi in S2 cells, our flow cytometric method should serve as a general tool for
      determining whether any eukaryotic protein is subject to replication-coupled
      protein destruction.

PMID- 21870295
TI  - Assessing G1-to-S-phase progression after genotoxic stress.
AB  - Maintenance of genomic integrity is critical for the survival of organisms. Thus,
      mammalian cells employ a complex DNA damage response that can sense and repair
      DNA damage. One important aspect of the cellular DNA damage response is the
      activation of checkpoints that result in cell cycle arrest. In this chapter we
      present methods for the induction of genotoxic stress. Additionally, we describe
      methods for studying the progression of cells from G(1) to S phase after
      genotoxic stress.

PMID- 21870296
TI  - Indirect immunofluorescence for monitoring spindle assembly and disassembly in
      yeast.
AB  - In yeast like all eukaryotes, microtubules are a crucial element of the mitotic
      spindle that separates the genetic material during cell division. The assembly
      status and position of the mitotic spindle, as well as cytoplasmic microtubules,
      can be monitored easily using indirect immunofluorescence with antibodies against
      tubulin. A detailed protocol is described for Saccharomyces cerevisiae that
      involves the fixation of actively growing cells, removal of the cell wall by
      enzymatic digestion, post-fixation, and the application of tubulin antibodies.
      The use of secondary antibodies conjugated to a fluorescent moiety permit
      visualization of the mitotic spindle by fluorescence microscopy. Methods for the
      reduction of background and pre-absorption of antibodies are discussed.

PMID- 21870297
TI  - Detecting recruitment of DNA damage response factors through the eChIP approach.
AB  - DNA interstrand crosslinks (ICLs) are lesions that covalently link the two
      strands of DNA. This type of DNA damage represents one of the most complex DNA
      lesions whose repair mechanisms remain largely unclear. Uncovering proteins
      involved in the processing of ICLs and understand how they interact with the
      damaged DNA in vivo is crucial for the understanding of DNA interstrand crosslink
      repair processes. Moreover, the presence of an ICL during S phase constitutes the
      most severe blockage to DNA synthesis and results in prolonged stall of
      replication forks. The mechanisms of resolving a stalled replication fork is
      poorly understood because proper experimental platforms are lacking. To enable
      detection of protein recruitment to site-specific ICLs and to ICL-stalled
      replication forks, we established a novel eChIP (abbreviation for episomal
      chromatin immunoprecipitation) assay system to study the association of various
      DNA damage repair proteins with ICL lesions in vivo. This EBV episomal
      replication-based assay allows detection of protein enrichment at ICLs at the
      molecular level. Since ICLs cause replication fork blockage in an episomally
      replicating plasmid, the eChIP approach also allows the study of DNA damage
      response factor recruitment, such as checkpoint initiation factors, to stalled
      DNA replication forks. With proper adaptation, the eChIP approach may be employed
      to study other site-specific DNA lesions such as UV photoproducts and oxidative
      damage in vivo.

PMID- 21870298
TI  - Methods to study cancer therapeutic drugs that target cell cycle checkpoints.
AB  - Cell cycle checkpoints operating through a network of multiple signaling pathways
      provide a key mechanism for self-defense of cells against DNA damage caused by
      various endogenous or environmental stresses. In cancer treatment, checkpoints
      are activated in response to diverse DNA-damaging agents and radiation, thus
      representing a critical barrier limiting therapeutic efficacy. To date, despite
      efforts to target other components of checkpoint signaling pathways (e.g., ATM,
      Chk2, Wee1), checkpoint kinase 1 (Chk1) remains the most important target for
      cancer treatment because of its functional association with essentially all cell
      cycle checkpoints. The primary goal in the development of therapeutic agents
      targeting cell cycle checkpoints continues to be improving the anti-cancer
      activity of chemo- and radiotherapy by abrogating checkpoints necessary for DNA
      repair, thereby killing cancer cells through engagement of the apoptotic
      machinery.

PMID- 21870299
TI  - Survival predictors for second-line chemotherapy in Caucasian patients with
      metastatic gastric cancer.
AB  - PRINCIPLES: There are very limited data suggesting a benefit for second-line
      chemotherapy in advanced gastric cancer. Therefore, the number of patients who
      receive further treatment after failure of first-line chemotherapy varies
      considerably, ranging from 14% to 75%. In the absence of a demonstrated survival
      benefit of second-line chemotherapy, appropriate selection of patients based on
      survival predictors is essential. However, no clinico-pathologic parameters are
      currently widely adopted in clinical practice. We looked exclusively at Caucasian
      patients with metastatic gastric cancer treated with second-line chemotherapy to
      see if we could establish prognostic factors for survival. METHODS: This study
      retrospectively evaluated 43 Caucasian patients with metastatic gastric cancer
      treated with second-line chemotherapy at the Geneva University Hospital.
      Prognostic values of clinico-pathologic parameters were analysed by Cox
      regression for overall survival (OS). RESULTS: Univariate analysis found three
      variables to be associated with survival: progression-free survival (PFS) at
      first-line chemotherapy of more than 26 weeks (hazard ratio (HR) = 0.33,
      confidence interval (CI) 95% 0.16-0.65, p = 0.002), previous curative surgery (HR
      = 0.51, CI 95% 0.27-0.96, p = 0.04) and carcinoma embryonic antigen (CEA) >6.5
      MUg/l (HR = 1.97, CI 95% 1.06-3.65, p = 0.03). CONCLUSIONS: In line with
      published data, sensitivity to previous chemotherapy identifies Caucasian
      patients who will survive the longest following second-line chemotherapy. A low
      tumour burden and previous curative gastrectomy also seem to have a positive
      prognostic value.

PMID- 21870300
TI  - No association between herpes simplex virus 1 and cardiac myxoma.
AB  - PRINCIPLES: Cardiac myxoma is the most commonly diagnosed cardiac tumour.
      Infection of herpes simplex virus 1 (HSV1) has been postulated to be a factor for
      this pathologic entity. The aim of the current study was to evaluate the
      association between HSV 1 and myxoma occurrence. METHODS: Between 1965 and 2005,
      70 patients (36 female, mean age: 52.6 years) underwent a resection of myxoma.
      Selected variables such as hospital mortality and morbidity were studied. A
      follow-up (FU; mean FU time: 138 +/- 83 months) was obtained (76% complete).
      Immunohistological studies with monoclonal antibodies against HSV type 1 were
      performed on tumour biopsies of 40 patients. RESULTS: The mean age was 53 +/- 16
      years (range 23 to 84 years, 51% female). Of the investigated population, 31
      (44%) were in New York Heart Association (NYHA) class III-IV. Mitral valve
      stenosis was identified in 14 patients (20%), and in 25 (36%) patients mitral
      valve was insufficient. During hospitalisation 3 patients suffered from a
      transient neurological disorder, and in addition to myxoma resection 18 (25.7%)
      patients had to undergo an additional intervention. The overall survival rate was
      91% at 40 years. There was no early postoperative mortality in follow-up,
      although 4 patients died and 2 patients had been re-operated on for recurrent
      myxomas after 2 and 9 years. Immunohistology revealed no positive signals for HSV
      1 antigens among the 40 analysed cases. CONCLUSION: Complete surgical resection,
      septum included, was the treatment of choice and mandatory to prevent relapse.
      Peri-operative morbidity and mortality over 40 years remained low, and no
      association between HSV infection and occurrence of cardiac myxoma was found.

PMID- 21870301
TI  - Feasibility and safety of propofol sedation in flexible bronchoscopy.
AB  - BACKGROUND: Propofol is a sedative-hypnotic with a rapid onset of action. There
      are only limited data evaluating propofol for flexible bronchoscopy. We analysed
      the feasibility and safety of propofol for bronchoscopy in a high output tertiary
      care centre. METHODS: Prospective data on patients undergoing flexible
      bronchoscopy at the University Hospital Basel, Switzerland, were analysed.
      Patient demographics, ASA class, Mallampati class, indication for bronchoscopy,
      bronchoscopic procedures, duration of examination, medication requirements, minor
      and major adverse events, haemodynamic parameters, as well as cough scores during
      the procedure were documented. Patients were followed up to discharge from the
      bronchoscopy suite. RESULTS: Data from 440 patients with a mean age 60 years (+/
      15.5, 260 male) were analysed. The main indication for bronchoscopy was a
      suspicion of malignancy. The most common diagnostic procedures were
      bronchoalveolar lavage in 253 cases (31.5%) and bronchial washing in 174 cases
      (21.7%). The mean duration of the procedure was 19.6 min (+/-12.08). The mean
      propofol dose was 200 mg (+/-107.5) corresponding to 2.89 mg/kg (+/-1.70). Minor
      adverse events included oxygen desaturation in 72 (16.4%), hypotension in 68
      (15.4%) and minor bleeding in 11 (2.5%) patients. No major adverse events were
      recorded. The median decline in systolic blood pressure after initiation of
      sedation was 14 mm Hg (3-28). A drop in systolic blood pressure greater than 20
      mm Hg was observed in 166 of the 440 patients (37%). CONCLUSION: Propofol
      sedation for flexible bronchoscopy is feasible and safe.

PMID- 21870302
TI  - Mental health of the population exposed to radiation after nuclear crisis: a
      topic to be discussed in psychiatry.

PMID- 21870303
TI  - An examination of mobbing and burnout of residents.
AB  - AIM: Mobbing and burnout in human resources management are important topics in
      labor psychology. It is important to research the levels of mobbing and burnout
      of human resources in the health sector, primarily in doctors. Although there
      have been some studies on the mobbing and burnout of doctors, there has been a
      limited number of studies on the relationship between mobbing and burnout in the
      health sector. This study aims to examine the relationship between mobbing and
      burnout (emotional exhaustion, depersonalization, personal accomplishment) levels
      of resident doctors at a public university research and training hospital in
      Turkey and to investigate whether mobbing and burnout levels vary significantly
      according to gender, marital status, medical branch and age. METHOD: This study
      was conducted on resident doctors at the Ondokuz Mayis University Research and
      Training Hospital between 01.04.2009 and 30.06.2009. Legal permission for the
      study was received from the Rector's Office of Ondokuz Mayis University. The
      Maslach Burnout Inventory for measuring burnout levels in doctors and the Leymann
      Inventory of Psychological Terror for measuring doctors' mobbing levels were the
      research instruments employed. Sampling was not used in this study. The aim was
      to administer the research instruments to all the residents (the universe of this
      study consisted of 510 assistant doctors). 52.94 % of residents responded to all
      of the questions in these instruments. In the data analysis, a t-test, ANOVA,
      regression analysis and descriptive statistics were used. FINDINGS: At the end of
      the analyses, it was found that the mean mobbing level of residents is 1.97; the
      mean emotional exhaustion level of residents is 2.97; the mean level of
      depersonalization is 2.95; and the mean level of personal accomplishment is 2.94.
      Mobbing and burnout levels of residents vary significantly in terms of medical
      branch. CONCLUSION: This study indicated that there are relationships between
      mobbing, emotional exhaustion, depersonalization and personal accomplishment.
      Mobbing is a significant regressor for emotional exhaustion, depersonalization
      and personal accomplishment in this study.

PMID- 21870304
TI  - The prevalence of social phobia, and its impact on quality of life, academic
      achievement, and identity formation in university students.
AB  - PURPOSE: The present study aimed to determine the prevalence of social phobia,
      and the sociodemographic variables, substance use patterns, and comorbid
      psychiatric disorders associated with it. The impact of social phobia on quality
      of life, academic achievement, and identity formation were also examined.
      MATERIALS AND METHODS: The study was conducted between 01 March and 01 June 2008,
      and included 700 undergraduate students at Adnan Menderes University. A
      sociodemographic data form, the Liebowitz Social Anxiety Scale (LSAS), World
      Health Organization Quality of Life-Brief Form, Turkish Version (WHOQoL-BREF-TR),
      and Instrument for Assessing Identity Confusion (IFAIC) were administered to the
      participants. FINDINGS: In all, 20.9% of the participants had social phobia
      during the previous year and 21.7% had social phobia for a lifetime. In total,
      74.6% of those that had social phobia during the previous year and 76.5% of those
      that had social phobia for their whole lives also had a specific social phobia.
      There was a significant difference between the participants with generalized
      social phobia or a specific social phobia, and those without social phobia, in
      terms of LSAS and IFAIC scores. Logistic regression analysis showed that the risk
      of social phobia was 1.7-fold higher among the females than males, 1.5-fold
      higher among those that lived in cities for the last 15 years than those that
      lived in towns, 1.9-fold higher among those that lived in cities for the last 15
      years than those that lived in villages, and 1.8-fold higher among those that had
      relatives with a psychiatric illness than those that didn't. Higher socioeconomic
      status was negatively correlated with the prevalence of social phobia. Cigarette
      smoking was more prevalent among the students without social phobia and suicidal
      ideation was more prevalent among the students with social phobia. WHOQOL-BREF-TR
      scores showed that students without social phobia had significantly higher
      quality of life quality than those with social phobia. Self-reported academic
      performance did not significantly differ between the students with social phobia
      and those without social phobia. CONCLUSION: Social phobia research may be
      limited, but was highly prevalent among the university students in the present
      study and had significant negative effects on identity formation and quality of
      life.

PMID- 21870305
TI  - Distinctive sociodemographic, clinical and temperament characteristics of bipolar
      I, bipolar-II and major depressive disorders.
AB  - INTRODUCTION: Mood disorders are one of the significant mental disorders that
      decrease the quality of human life and disrupt the psychosocial functionality and
      interpersonal relationships. Recently, studies have suggested that affective
      temperaments are factors that determine the emergence and characteristics of mood
      disorders. METHODS: 150 patients total were enrolled in the study, which aimed to
      compare the temperament, clinical and sociodemographic characteristics of 50 BD
      I, 46 BD-II and 54 MDD patients. In order to determine clinical and
      sociodemographic features, we administered the SKIP-TURK structured follow-up
      questionnaire, the Hamilton Depression Rating Scale (HDRS), the Young Mania
      Rating Scale (YMRS) and the TEMPS-A temperament rating scale for all patients.
      RESULTS: The following clinical, sociodemographic and temperament characteristics
      were evaluated: such as history of psychiatric disorder of first and second
      degree relatives, comorbid hypothyroidism, age of onset of the mood disorder
      symptoms, the nature of the first episode of the mood disorder, seasonal course,
      mean duration of the episode, total number of episodes, severity of the mood
      episodes, and total number of hospitalizations. CONCLUSION: Our results
      demonstrated that some sociodemographic, clinical and affective temperament
      characteristics may be good predictors for early diagnoses and treatment of BD
      and MDD.

PMID- 21870306
TI  - The effects of infertility on sexual functions and dyadic adjustment in couples
      that present for infertility treatment.
AB  - OBJECTIVE: The aim of this study was to determine the effects of infertility on
      sexual functions and dyadic adjustment in infertile couples that seek infertility
      treatment. MATERIALS AND METHODS: The Beck Depression Inventory (BDI), Golombok
      Rust Inventory of Sexual Satisfaction (GRISS), and Dyadic Adjustment Scale (DAS)
      were administered to the infertility group (n = 220) and control group (n = 110).
      None of the study participants had an Axis I psychiatric disorder. RESULTS: There
      wasn't a significant difference in BDI score between the 2 groups. None of the
      study participants had clinical depression. Men in both groups reported more
      problems according to GRISS total scale and subscale scores (except the avoidance
      subscale) than the women. Women in both groups reported more problems according
      to GRISS avoidance subscale score than did the men. Men in the control group
      reported more problems on the GRISS frequency subscale, as compared men in the
      infertile group. Women in the control group reported more problems based on GRISS
      total score, and GRISS frequency, satisfaction, touch, and avoidance subscale
      scores, as compared to the women in the infertile group. The men in the infertile
      group were more satisfied with dyadic adjustment than the women in the infertile
      group. The men and women in the control group had higher DAS total score, and DAS
      consensus and emotional expression subscale scores. CONCLUSION: The differences
      in sexual functions between the infertile and control groups were not
      significant. Both women and men in the infertility group reported more dyadic
      adjustment problems than those in the control group.

PMID- 21870307
TI  - Investigation of the reliability of the "reading the mind in the eyes test" in a
      Turkish population.
AB  - OBJECTIVE: The "Reading the Mind in the Eyes Test"(RMET) is one of the most
      widely used tasks for examining the Theory of Mind. In this study, the goal was
      to determine the reliability of a Turkish version of the RMET and the
      distribution of the results in a healthy population. METHOD: The original test is
      made up of 36 pictures of solely the eye region of different individuals.
      Subjects are asked to choose the option that best describes the mental state of
      individual in the picture. After 3 piloting studies each conducted with different
      sets of 8 people, 2 items (25 and 35) in which most of the subjects consistently
      replied to foil words, were excluded in final step. 117 healthy volunteers were
      given the test, and 70 of these individuals were re-tested two weeks later. The
      Bland and Altman method was used to examine test re-test reliability RESULTS: The
      mean value of the number of correct responses was 24.46 (SD=3.44) for the test
      and 24.13 (SD=4.36) for the re-test. No significant difference was shown between
      test and re-test results (p=0.815). After excluding items 19 and 21 which failed
      to show reliability, the mean correct response rates were 23.64 (SD=3.38) and
      23.40 (SD=4.32), respectively. The educational level significantly affected the
      correct response rates. CONCLUSION: The Turkish version of the RMET was found to
      be reliable in a healthy population. The educational level should be taken into
      account. The 32-item version of the Turkish RMET can be used to evaluate the
      social, cognitive and emotional processes in adults.

PMID- 21870308
TI  - Anxiety sensitivity and its importance in psychiatric disorders.
AB  - Anxiety sensitivity refers to the extent of beliefs that anxiety symptoms or
      arousal can have harmful consequences. There is growing evidence for anxiety
      sensitivity as a risk factor for anxiety disorders. Anxiety sensitivity is
      elevated in panic disorder as well as other anxiety disorders. It is thought to
      contribute to the maintenance and severity of anxiety symptoms. Studies have
      shown that anxiety sensitivity more specifically predicts the future occurrence
      of panic attacks. The Anxiety Sensitivity Index (ASI), which measures the
      construct of anxiety sensitivity, has three subscales, namely, the ASI-Physical
      subscale, ASI-Social subscale and ASI-Mental Incapacitation Concerns subscale.
      The dimension reflecting "fear of physical sensations" of anxiety sensitivity is
      the most predictive one of panic attacks and panic disorder. Research on the ASI
      has demonstrated that persons diagnosed with post-traumatic stress disorder,
      generalized anxiety disorder, obsessive-compulsive disorder, and social anxiety
      disorder all had ASI scores higher than normal controls. Depression was
      speculated to hold a positive correlation to high anxiety sensitivity scores. The
      relationships between anxiety sensitivity, alcohol and substance use disorders
      are still unknown. There is evidence that anxiety sensitivity is related with
      "drinking used as a way of coping". Since anxiety sensitivity is a cognitive
      construct, it should be taken into consideration when evaluating patients with
      anxiety and psychotherapeutic formulations.

PMID- 21870309
TI  - Priapism due to a single dose of quetiapine: a case report.
AB  - Priapism is characterized by a prolonged and painful erection in the absence of
      sexual desire and arousal. Priapism is a rare and serious side effect of
      psychotropic drugs, and is thought to be attributable to blockage of alpha-1
      adrenergic receptors in the corpus cavernosum. Although priapism is commonly
      associated with typical antipsychotics, there are some (but not many) case
      reports of priapism due to atypical antipsychotics. This side effect has been
      reported in patients taking ziprasidone, risperidone, clozapine, quetiapine,
      aripiprazole, and olanzapine. Not all antipsychotics bind to alpha-1 adrenergic
      receptors with the same intensity; as compared to other antipsychotics,
      quetiapine has an intermediate affinity. Priapism could be considered an
      idiosyncratic reaction, because it is correlated neither with the dose nor
      duration of psychotropic drug use. Herein we present a case of priapism caused by
      a single 300-mg dose of quetiapine, and a brief review priapism in the light of
      this case.

PMID- 21870310
TI  - Galactorrhea during duloxetine treatment: a case report.
AB  - High prolactin hormone level in the blood is known as hyperprolactinemia. The
      most common symptom of hyperprolactinemia is galactorrhea, in which spontaneous
      milky discharge is seen from all ducts of the 2 mammary glands. Galactorrhea
      occurs due to different medical conditions, including the use of antidepressant
      medications. Herein we report a hyperprolactinemia case with galactorrhea due to
      duloxetine treatment for depression.

PMID- 21870311
TI  - [Depression in obstructive sleep apnoea syndrome].

PMID- 21870312
TI  - [The short version of the Brief Symptom Inventory (BSI -18): preliminary
      psychometric properties of the German translation].
AB  - The short version of the Brief Symptom Inventory (BSI-18) is an easily
      applicable, reliable and valid self-report measure in wide international use. It
      assesses the syndroms of somatisation, depression and anxiety by means of 6 items
      each. For the psychometric evaluation of the German translation, undergraduate
      students, non-clinical subjects and psychosomatic outpatients were administered
      the BSI-18. Across these populations, all scales showed satisfactory to good
      internal consistencies (Cronbachs alpha ranged between 0.63 and 0.93). The item
      total correlation as item discrimination index was sufficiently high,
      patricularly in the patient sample (rit >= 0.40). The correlations of the BSI-18
      with measures of similar dimensions were moderate to high indicating a good
      convergent validity. Criterion-related validity was established in so far that
      patients scored significantly higher in all BSI-18 scales than did the non
      clinical samples. With some exceptions, the German translation of the BSI-18 has
      similarly good psychometric qualities as the American original.

PMID- 21870313
TI  - [Early onset psychosis: rationale and concept of a cognitive-behavioral
      intervention].
AB  - Early onset psychoses (EOP, age of onset between age 14 and 18 years) are known
      to be associated with a poorer outcome than adult onset psychoses, both in terms
      of psychotic symptoms and social remission. For adult patients with psychosis,
      numerous cognitive-behavioral interventions have proven their effectiveness in
      recent years. This contrasts with a dearth of findings for EOP, even though it
      can be considered as a variant of adult onset psychosis. Thus, we have developed
      a cognitive-behavioral therapy intervention that was specifically adapted to the
      characteristics and needs of young people suffering from psychosis. The concept
      of the intervention is outlined in the present article. Acceptability and
      feasibility of the intervention are currently undergoing evaluation in a
      randomised, controlled pilot study.

PMID- 21870314
TI  - [Obstructive sleep apnoea syndrome as the cause of atypical depression].
AB  - Sleep apnoea is a common disorder presenting with somatic comorbidities and
      psychiatric symptoms. This case report describes a 43-year-old man with an
      organic depressive disorder due to obstructive sleep apnoea. Initially, an
      atypical depressive episode or schizophrenic residual syndrome had been
      considered likely diagnoses; subsequent polysomnography results, however,
      suggested obstructive sleep apnoea instead. Upon nasal continuous positive airway
      pressure (nCPAP), the respiratory distress symptoms improved. The case report
      highlights the association between sleep disturbances and depressive symptoms. In
      patients presenting with symptoms of atypical depression and excess body weight
      sleep apnoea should be considered.

PMID- 21870315
TI  - [Forensic-psychiatric assessment of pedophilia].
AB  - The present paper illustrates the approach of a forensic psychiatric expert
      witness regarding the assessment of pedophilia. In a first step it is inevitable
      to differentiate if the defendant is suffering from pedophilia or if the alleged
      crime might have been committed because of other motivations (antisociality,
      sexual activity as redirection, impulsivity). A sound diagnostic assessment is
      indispendable for this task. In a second step the level of severity needs to be
      gauged in order to clarify whether the requirement of the entry criteria of SS
      20, 21 of the German penal code are fulfilled. In a third step, significant
      impairments of self-control mechanisms need to be elucidated. The present article
      reviews indicators of such impairments regarding pedophilia. With respect to a
      mandatory treatment order (S 63 German penal code) or preventive detention (S 66
      German penal code) the legal prognosis of the defendant needs to be considered.
      The present paper gives an overview of the current state of risk assessment
      research and discusses the transfer to an individual prognosis critically.

PMID- 21870316
TI  - [Diagnosis and therapy of chronic vertigo syndroms].

PMID- 21870317
TI  - Combined effects of whole-body vibration, resistance exercise, and vascular
      occlusion on skeletal muscle and performance.
AB  - The purpose of this study was to evaluate the effects of a new high-intensity
      training modality comprised of vibration exercise with superimposed resistance
      exercise and vascular occlusion (vibroX) on skeletal muscle and performance.
      Young untrained women were randomized to either train in a progressive mode on 3
      days per week for 5 weeks ( N=12) or to maintain a sedentary lifestyle ( N=9).
      VibroX increased peak cycling power (+9%, P=0.001), endurance capacity (+57%,
      P=0.002), ventilatory threshold (+12%, P<0.001), and end-test torque (+15%,
      P=0.002) relative to the sedentary group. Training load increased by 84.5% (
      P<0.001) after vibroX. The increases were paralleled by increases in myosin heavy
      chain type 1 vastus lateralis muscle fiber cross-sectional area (+14%, P=0.031)
      and proportion (+17%, P=0.015), thigh lean mass (+4%, P=0.001), capillary-to
      fiber ratio (+14%, P=0.003), and cytochrome c oxidase activity. Conversely,
      maximal values for oxygen consumption, cardiac output, isokinetic leg extension
      power and jumping power remained unaffected. Notably, vastus lateralis muscle
      adaptations were achieved with a very low weekly training volume. We conclude
      that vibroX quickly increases muscle (fiber) size, capillarization, and oxidative
      potential, and markedly augments endurance capacity in young women.

PMID- 21870318
TI  - Measurement of the Optic Nerve Sheath Diameter in Children: Comparison Between
      Transbulbar Sonography and Magnetic Resonance Imaging.
AB  - PURPOSE: To evaluate the accuracy of measurements of the optic nerve sheath
      diameter (ONSD) in children by comparing transbulbar sonography with magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: 65 children (age: 3 mo-17 y; mean
      age: 11.3 y) underwent MR imaging of the brain including a heavily T 2-w sequence
      of the orbit and transbulbar sonography using a 17 MHz linear array transducer.
      Measurements of the ONSD were performed retrospectively by two experienced
      readers and all images were evaluated regarding the image quality. Bland-Altman
      Plots were produced to assess the accuracy of measurements. The correlation
      between readers and between MR imaging and transbulbar sonography was calculated
      by the concordance correlation coefficient (CCC). RESULTS: Overall the mean
      values of the ONSD for MRI (5.86 +/- 0.66 mm) and transbulbar sonography (5.86 +/
      0.71 mm) were identical. There was a high correlation between readers for
      measurements of the ONSD both for transbulbar sonography (CCC = 0.93) as well as
      for MRI (CCC = 0.9). Comparing the measurement values between transbulbar
      sonography and MRI, the correlation of ONSD values was good to moderate with a
      high dependency on image quality (CCC [0.31, 0.68]). CONCLUSION: We were able to
      demonstrate that the ONSD values of transbulbar sonography in children correlate
      well with MRI if the relevant anatomic structures are depicted and the measuring
      points are set correctly. Based on the findings of our study, it seems necessary
      to define normal and cut-off values for the ONSD in children again to finally
      assess the clinical relevance of the ONSD as a noninvasive parameter for the
      evaluation of intracranial pressure.

PMID- 21870319
TI  - Altered cerebral collateralization in patients with left brachiocephalic trunk
      occlusion and a right descending aorta.

PMID- 21870320
TI  - Triterpenes and triterpenoid saponins from the leaves of Ilex kudincha.
AB  - One new triterpene, kudinchalactone A (1), and four new triterpenoid saponins,
      ilekudinchosides A-D (2- 5), were isolated from the leaves of Ilex kudincha C. J.
      Tseng along with eight known triterpenoids. These new compounds were elucidated
      by spectroscopic methods including 1D and 2D NMR, HR-TOF-MS, and CD spectra.
      Compounds 2, 3, 12, and 13 showed antibacterial activities against Staphylococcus
      aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 21870321
TI  - Flavone C-glycosides from the leaves of Lophatherum gracile and their in vitro
      antiviral activity.
AB  - Four new flavone C-glycosides, luteolin 6-C-alpha-L-arabinopyranosyl-7-O-beta-D
      glucopyranoside, apigenin 6-C-beta-D-galactopyranosiduronic acid (1 -> 2)-alpha-L
      arabinopyranoside, luteolin 6-C-beta-D-galactopyranosiduronic acid (1 -> 2)-alpha
      L-arabinopyranoside, and luteolin 6-C-beta-D-glucopyranosiduronic acid (1 -> 2)
      alpha-L-arabinofuranoside, along with three known ones, were isolated from the
      leaves of Lophatherum gracile. The structures of the new compounds were
      elucidated by extensive spectroscopic methods as well as acid hydrolysis. All the
      flavone glycosides isolated from this plant were screened for their in vitro
      antiviral activity against respiratory syncytial virus (RSV) with cytopathic
      effect (CPE) reduction assay, and several flavone 6-C-monoglycosides showed
      potent in vitro anti-RSV effect.

PMID- 21870323
TI  - Oral administration of chios mastic gum or extracts in mice: quantification of
      triterpenic acids by liquid chromatography-tandem mass spectrometry.
AB  - Chios mastic gum, the resin obtained as an exudate from the trunk and branches of
      Pistacia lentiscus L var. chia, is used extensively as a constituent of herbal
      drugs or functional foods. The oral absorption of its major constituents still
      remains unclear. In the context of identifying the features of mastic gum that
      are responsible for either therapeutic effects or effects of nutritional value, a
      methodology based on high-performance liquid chromatography (HPLC) coupled to
      tandem mass spectrometry (MS/MS) was developed and applied for the quantification
      of mastic gum triterpenic acids, 24Z-isomasticadienonic acid (IMNA), and 24Z
      isomasticadienolic acid (IMLA) in mouse plasma. The specific compounds were
      selected based on their biological activity and potential against Helicobacter
      pylori. Concentrations were determined simultaneously in mouse plasma after oral
      administration of mastic gum or total mastic extract without polymer (TMEWP) in
      order to evaluate the role of the natural polymer, poly-beta-myrcene, in the
      absorption process. Following TMEWP administration in mice, circulating IMNA and
      IMLA plasma levels were significantly higher (approximately 10-fold) in
      comparison to IMNA and IMLA plasma levels following total mastic gum
      administration (CMG), suggesting that the polymer plays a critical role in the
      absorption process. More specifically following TMEWP administration, Cmax plasma
      values were 3300 +/- 859 ng/mL for IMNA and 163 +/- 58 ng/mL for IMLA. In
      comparison, following CMG administration, Cmax plasma values were 329 +/- 57
      ng/mL for IMNA and 28 +/- 8 ng/mL for IMLA. The methodological approaches
      presented in this study, along with the findings, offer valuable information on
      the availability of bioactive components following ingestion of mastic and
      facilitate the uses of mastic either as an ingredient of functional foods or as a
      herbal drug.

PMID- 21870322
TI  - Effects of chemically characterized fractions from aerial parts of Echinacea
      purpurea and E. angustifolia on myelopoiesis in rats.
AB  - Echinacea species are used for beneficial effects on immune function, and various
      prevalent phytochemicals have immunomodulatory effects. Using a commercial E.
      purpurea (L.) Moench product, we have evaluated the myelopoietic effect on bone
      marrow of rats treated with various extracts and correlated this with their
      chemical class composition. Granulocyte/macrophage-colony forming cells (GM-CFCs)
      from femurs of female Sprague-Dawley rats were assessed at 24 h after 7 daily
      oral treatments. A 75% ethanolic extract at 50 mg dried weight (derived from 227
      mg aerial parts) per kg body weight increased GM-CFCs by 70% but at 100 mg/kg was
      without effect. Ethanolic extracts from aerial parts of E. angustifolia DC. var.
      angustifolia and E. purpurea from the USDA North Central Regional Plant
      Introduction Station increased GM-CFCs by 3- and 2-fold, respectively, at 200
      mg/kg (~1400 mg/kg plant material). Extract from another USDA E. angustifolia was
      inactive. Proton and APT NMR, MS, and TLC indicated alkylamides and caffeic-acid
      derivatives (CADs) present in ethanolic extracts of both the commercial and USDA
      derived material. Cichoric and caftaric acids were prominent in both E. purpurea
      ethanolic extracts but absent in E. angustifolia. Aqueous extract of the
      commercial material exhibited polysaccharide and CAD signatures and was without
      effect on GM-CFCs. A methanol-CHCl3 fraction of commercial source, also inactive,
      was almost exclusively 1:4 nonanoic: decanoic acids, which were also abundant in
      commercial ethanolic extract but absent from USDA material. In conclusion, we
      have demonstrated an ethanolextractable myelostimulatory activity in Echinacea
      aerial parts that, when obtained from commercial herbal supplements, may be
      antagonized by medium-chain fatty acids presumably derived from a non-plant
      additive.

PMID- 21870324
TI  - Anti-inflammatory xanthones from the twigs of Hypericum oblongifolium wall.
AB  - Two new xanthonolignoids, hypericorin A (1) and hypericorin B (2), along with
      five known new source compounds, a xanthonolignoid, kielcorin (3), 4-hydroxy-2,3
      dimethoxyxanthone (4), 3,4,5-trihydroxyxanthone (5), 1,3-dihydroxy-5
      methoxyxanthone ( 6) and 1,3,7-trihydroxyxanthone (7), were isolated from the
      stems (twigs) of Hypericum oblongifolium Wall. The structures of the new
      compounds were deduced on the basis of spectroscopic techniques (EI-MS, HREI-MS,
      (1)H NMR, (13)C NMR, HMQC, HMBC, and NOESY). We also report herein for the first
      time the single crystal X-ray structure of compound 6. Compounds 1- 7 were
      screened for their IN VITRO anti-inflammatory (respiratory burst) inhibiting
      activities using isolated human neutrophils; compounds 1, 2, 3, 5, and 7 showed
      significant activities (IC (50) = 816.23 +/- 73.30, 985.20 +/- 55.80, 965.21 +/-
      65.80, 907.20 +/- 50.80, 975.20 +/- 81.10 uM, respectively), compound 6 showed
      moderate activity (IC (50) = 2500.85 +/- 50.50 uM), while compound 4 was totally
      inactive at 1000 ug/mL as compared to the positive control used, indomethacin (IC
      (50) = 757.99 +/- 5.90 uM), and aspirin (IC (50) = 279.44 +/- 4.40 uM). Compound
      4 was also inactive in comparison with other tested Hypericum compounds.

PMID- 21870325
TI  - 17-O-acetyl,10-hydroxycorynantheol, a selective antiplasmodial alkaloid isolated
      from Strychnos usambarensis leaves.
AB  - In the course of our investigations on Strychnos usambarensis leaves in order to
      isolate isostrychnopentamine, the main alkaloid responsible for the
      antiplasmodial activity of the plant, a new tertiary indolic alkaloid has been
      isolated: 17-O-acetyl,10-hydroxycorynantheol 1. Its structure was determined by
      means of spectroscopic and spectrometric methods such as UV, IR, CD, NMR, and ESI
      MS. 17-O-acetyl,10-hydroxycorynantheol 1 is one of the most active monomeric
      indole alkaloids known to date showing an in vitro activity against Plasmodium
      falciparum close to 5 uM and a high selectivity.

PMID- 21870326
TI  - [Proximal row carpectomy and replacement of the proximal pole of the capitate by
      means of a pyrocarbon cap (RCPI) in advanced carpal collapse].
AB  - The results of 5 patients suffering from advanced carpal collapse after proximal
      row carpectomy and replacement of the proximal pole of the capitate by means of a
      pyrocarbon cap are presented.5 patients with an average age of 40.2 years (23-66
      years) suffering from advanced carpal collapse were treated by means of proximal
      row carpectomy and replacement of the proximal pole of the capitate between
      January 2005 and August 2008. Clinical and radiological follow-ups within an
      average post-operative period of 54.4 months (25-68 months) were conducted. For
      the assessment of the outcome the DASH score and the traditional Krimmer score
      were used.At the follow-up all patients were fully recovered and could expose the
      wrist to higher exertions. Radiologically the implants in 3 of 5 patients were
      found to be tight and at the original post-operative location in comparison with
      the post-operative X-rays. In 2 of 5 patients a mild seam of loosening was
      detected around the implant. In the traditional Krimmer score the patients
      reached 81 points (75-85 points) and in the DASH score 8 points (2.5-23.33
      points).The described results of the present procedure define it as an
      alternative in treating patients suffering from advanced carpal collapse as far
      as evidence from this small collective can be considered. The small seam of
      loosening around implants in 2 of 5 patients suggests that we may expect further
      loosening of implants in the long run. Larger patient collectives are necessary
      to confirm these provisional results.

PMID- 21870327
TI  - Detection of Merkel cell polyomavirus in Merkel cell carcinomas and small cell
      carcinomas by PCR and immunohistochemistry.
AB  - Recently, the clonal integration of a new human polyomavirus (Merkel cell
      polyomavirus or MCPyV) has been reported in Merkel cell carcinoma (MCC). In order
      to investigate the presence of MCPyV in small cell carcinomas (SCCs) and small
      round cell tumors (SRCTs), we collected formalin-fixed paraffin-embedded tissue
      specimens including 14 MCCs, 24 SCCs, 7 Ewing sarcoma/primitive neuroectodermal
      tumors (ES/PNETs) and 5 neuroblastomas. We also collected specimens of other
      cancers including 12 malignant melanomas, 10 breast, 10 ovarian and 20 gastric
      cancers. We used 3 primer sets for which the sequences were previously published
      (LT1, LT3, and VP1) and 3 newly designed primer sets (LT1-1, LT1-1a, and LT3a).
      Quantitative real-time PCR was also performed with the LTq primer set. Nested PCR
      using the LT3a primer set detected more cases of MCPyV infection in MCC. In
      total, 12 of 14 (85.7%) MCC cases were positive for MCPyV by PCR, which was
      consistent with published data. Some SCC specimens were also positive for MCPyV
      (37.5%) by PCR. PCR products from MCC and SCC cases showed premature truncation
      and frameshift mutation. Furthermore, one case of ES/PNET and one gastric
      carcinoma showed MCPyV DNA. However, MCPyV DNA and transcript were only detected
      in MCCs with quantitative real-time PCR analysis. In addition, 11 of 13 (84.6%)
      MCC cases and 6 of 23 (26.1%) SCC cases showed immunoreactivity with monoclonal
      antibodies against MCPyV large T-antigen. Considering both PCR and IHC results,
      MCPyV was detected in all MCCs tested. The presence of MCPyV in all MCC cases
      tested and in some SCC cases suggests that MCPyV may be involved in the malignant
      transformation.

PMID- 21870328
TI  - Pathological correlations between podocyte injuries and renal functions in canine
      and feline chronic kidney diseases.
AB  - Podocytes cover the glomerulus and their adjacent foot processes form a principal
      barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss
      and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this
      study, we analyzed the correlations between podocyte injuries and renal
      dysfunctions in domestic carnivores. Dogs and cats were divided into normal and
      CKD groups according to renal histopathology and plasma creatinine values.
      Immunostaining results showed that linear reactions of slit diaphragm molecules,
      e.g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all
      animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a
      granular pattern in the CKD group, and their intensities significantly decreased
      with the number of podocytes in the glomerulus. Moreover, the expression of
      nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis
      showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly
      lower than that in normal animals, and negatively correlated with creatinine.
      Although no significant correlation between renal dysfunction and podocyte injury
      was detected in cats, histoplanimetric scores of tubulointerstitial lesions in
      CKD cats were higher than those in both normal cats and diseased dogs.
      Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD
      animals. In conclusion, podocyte injuries such as podocytopenia and decreased
      expression of nephrin and ACTN4 in the glomerulus were more strongly correlated
      with renal dysfunction in dogs than in cats. These findings suggest that the CKD
      pathogenesis, especially susceptibilities to podocyte injuries, differed between
      dogs and cats.

PMID- 21870329
TI  - Daidzein effects on ACTH cells: immunohistomorphometric and hormonal study in an
      animal model of the andropause.
AB  - Daidzein is a potential natural alternative to estradiol during therapy of some
      malignancies in men. Besides weak inhibition of tyrosine kinase activity,
      daidzein has a sizeable inhibitory effect on calcium channels. The aim of this
      study was to examine the effects of daidzein on the immunohistomorphometric
      features of pituitary adrenocorticotropes (ACTH cells) and circulating levels of
      ACTH and corticosterone, in comparison with estradiol, in an animal model of the
      andropause. Sixteen-month-old Wistar rats were divided into sham operated (SO),
      orchidectomized (Orx), estradiol treated orchidectomized (Orx+E) and daidzein
      treated orchidectomized (Orx+D) groups. Estradiol (0.625 mg/kg/day) and daidzein
      (30 mg/kg/day) were administered subcutaneously for three weeks, while the SO and
      Orx groups received the vehicle alone. ACTH cells were identified by the
      peroxidase-antiperoxidase (PAP) immunohistochemical procedure. Peripheral
      circulating concentrations of ACTH and corticosterone were measured by
      immunoassay. Orchidectomy reduced (p<0.05) the cell volume and volume density of
      adrenocorticotropes by 11% and 16%, respectively, in comparison to SO rats. In
      Orx+E rats, the volume density of ACTH cells decreased (p<0.05) by 25%, but the
      circulating level of ACTH increased (p<0.05) by 29%, compared to Orx rats.
      Daidzein treatment significantly decreased (p<0.05): volume density of ACTH
      cells, circulating ACTH and corticosterone by 24%, 48% and 33%, respectively,
      compared to the Orx group. In conclusion, this study revealed that daidzein
      negatively modulated the immunohistomorphometric features of ACTH cells and,
      unlike estradiol, decreased ACTH and corticosterone secretion, in an animal model
      of the andropause.

PMID- 21870330
TI  - OA cartilage derived chondrocytes encapsulated in poly(ethylene glycol)
      diacrylate (PEGDA) for the evaluation of cartilage restoration and apoptosis in
      an in vitro model.
AB  - Osteoarthritis (OA) is characterized by cartilage attrition, subchondral bone
      remodeling, osteophyte formation and synovial inflammation. Perturbed homeostasis
      caused by inflammation, oxidative stress, mitochondrial dysfunction and
      proapoptotic/antiapoptotic dysregulation is known to impair chondrocyte survival
      in joint microenvironments and contribute to OA pathogenesis. However, the
      molecular mechanisms underlying the programmed cell death (apoptosis) of chondral
      cells are not yet well defined. The present study was conducted to evaluate
      apoptosis of chondrocytes from knee articular cartilage of patients with OA. The
      aim of this study was to investigate and compare the apoptosis through the
      expression of caspase-3 in tissue explants, in cells cultured in monolayer, and
      in cells encapsulated in a hydrogel (PEGDA) scaffold. Chondrocytes were also
      studied following cell isolation and encapsulation in poly(ethylene glycol)
      diacrylate (PEGDA) hydrogels. Specifically, articular cartilage specimens were
      assessed by histology (Hematoxlyn and Eosin) and histochemistry (Safranin-O and
      Alcian Blue). The effector of apoptosis caspase-3 was studied through
      immunohistochemistry, immunocytochemistry and immunofluorescence. DNA strand
      breaks were evaluated in freshly isolated chondrocytes from human OA cartilage
      using the TUNEL assay, and changes in nuclear morphology of apoptotic cells were
      detected by staining with Hoechst 33258. The results showed an increased
      expression of caspase-3 in tissue explants, in pre-confluent cells and after four
      passages in culture, and a decreased expression of caspase-3 comparable to
      control cartilage in cells encapsulated in hydrogels (PEGDA) after 5 weeks in
      culture. The freshly isolated chondrocytes were TUNEL positive. The chondrocytes
      after 5 weeks of culture in hydrogels (PEGDA) showed the formation of new hyaline
      cartilage with increased cell growth, cellular aggregations and extracellular
      matrix (ECM) production. This is of particular relevance to the use of OA cells
      and tissue engineering in the therapeutic approach to patients.

PMID- 21870331
TI  - GLUT1 and CAIX expression profiles in breast cancer correlate with adverse
      prognostic factors and MCT1 overexpression.
AB  - The goal of the present work was to evaluate the correlation of glucose
      transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX) with the monocarboxylate
      transporters 1 (MCT1) and 4 (MCT4) and their chaperone, CD147, in breast cancer.
      The clinico-pathological value of GLUT1 and CAIX was also evaluated. For that, we
      analysed the immunohistochemical expression of GLUT1 and CAIX, in a large series
      of invasive breast carcinoma samples (n=124), previously characterized for MCT1,
      MCT4 and CD147 expression. GLUT1 expression was found in 46% of the cases
      (57/124), while CAIX was found in 18% of the cases (22/122). Importantly, both
      MCT1 and CD147, but not MCT4, were associated with GLUT1 and CAIX expression.
      Also, GLUT1 and CAIX correlated with each other. Concerning the clinico
      pathological values, GLUT1 was associated with high grade tumours, basal-like
      subtype, absence of progesterone receptor, presence of vimentin and high
      proliferative index as measured by Ki-67. Additionally, CAIX was associated with
      large tumour size, high histological grade, basal-like subtype, absence of
      estrogen and progesterone receptors and presence of basal cytokeratins and
      vimentin expression. Finally, patients with CAIX positive tumours had a
      significantly shorter disease-free survival. The association between MCT1 and
      both GLUT1 and CAIX may result from hypoxia-mediated metabolic adaptations, which
      confer a glycolytic, acid-resistant and more aggressive phenotype to cancer
      cells.

PMID- 21870332
TI  - Effects of angiotensin (1-7) upon right ventricular function in experimental rat
      pulmonary embolism.
AB  - Right ventricular (RV) dysfunction contributes to poor clinical prognosis after
      pulmonary embolism (PE). The present studies evaluate the effects of angiotensin
      (1-7) (ANG (1-7)) upon RV function during experimental PE in rats. Circulating
      ANG II increased 8-fold 6 hr after PE (47+/-13 PE vs. 6+/-3 pg/mL, control,
      p<0.05). ACE2 protein was uniformly localized in the RV myocardium of control
      rats, but showed a patchy distribution with some cells devoid of stain after 6 or
      18 hr of PE. RV function decreased 18 hr after PE compared with control treated
      animals (19+/-4 vs. 41+/-1 mmHg, respectively, p<0.05; 669+/-98 vs. 1354+/-77
      mmHg/sec, respectively, p<0.05), while left ventricular function (LV) was not
      significantly changed. Animals treated with ANG (1-7) during PE showed improved
      RV +dP/dt and peak systolic pressure development to values not significantly
      different from control animals. Protection of RV function by ANG (1-7) was
      associated with improved arterial blood sO2, base excess and pH. Supplemental
      delivery of ANG (1-7) reduced the development of RV dysfunction, suggesting a
      novel approach to protecting RV function in the setting of acute experimental PE.

PMID- 21870333
TI  - Site differences of Toll-like receptor expression in the mucous epithelium of rat
      small intestine.
AB  - Toll-like receptors (TLRs) are known to recognize pathogen-associated molecular
      patterns and might function as receptors to detect microbes. In this study, the
      distribution of TLR-2, -4 and -9 were immunohistochemically investigated in the
      rat small intestine. As a result, TLR-2 was detected in the striated borders of
      villous columnar epithelial cells throughout the small intestine, except for the
      apices of a small number of intestinal villi. TLR-4 and -9 were detected in the
      striated borders of the villous columnar epithelial cells only in the duodenum.
      TLR-4-immunopositive minute granules were found in the apical cytoplasms of
      epithelial cells, subepithelial spaces and blood capillary lumina. TLR-2 and -4
      were detected in the striated borders of undifferentiated epithelial cells and in
      the luminal substances of the intestinal crypts throughout the small intestine,
      but TLR-9 was not detected in the crypts throughout the small intestine. Only TLR
      4 was detected in the secretory granules of Paneth cells in both the jejunal and
      ileal intestinal crypts. These findings suggest that duodenal TLRs might monitor
      indigenous bacteria proliferation in the upper alimentary tract, that TLR-2 might
      also monitor the proliferation of colonized indigenous bacteria throughout the
      small intestine, that the lack of TLR-2 at the villous apices might contribute to
      the settlement of indigenous bacteria, and that TLR-2 and -4 are secreted from
      intestinal crypts.

PMID- 21870334
TI  - sLea and sLex expression in colorectal cancer: implications for tumourigenesis
      and disease prognosis.
AB  - The glycoconjugates expressed by cancer cells frequently contain sialylated
      oligosaccharide chains. Among these oligosaccharides the sialyl Lewis a (sLe(a))
      and sialyl Lewis x (sLe(x)) antigens are found to be overexpressed in tumours of
      different origin. The current study assesses sLe(a) and sLe(x) expression in
      different colorectal specimens in order to establish the correlation of these
      biomarkers with both malignant transformation of colorectal mucosa and the
      progression of colorectal cancer (CRC). Healthy disease-free and inflammatory
      mucosa specimens showed no presence of the antigens. sLe(a) was expressed in 6.7%
      of the healthy tissue from CRC patients, in 20.8% of the adenomas, and in 33.3%
      and 42.6% of the transitional tissue and tumour tissue, respectively. sLe(x)
      expression was observed in 6.7% of the healthy tissue from CRC patients, in 27.0%
      of the adenomas, and in 25.6% and 74.8% of the transitional and the tumour
      tissue, respectively. The expression of the sLe(a) and sLe(x) antigens was
      correlated in adenomas, as well as in healthy and tumour tissue from CRC.
      Moreover, the high expression of sLe(x) in adenomas was correlated with a high
      degree of dysplasia (p=0.042). Finally, the survival analysis suggested that
      sLe(a) expression may be a prognostic factor for predicting disease-free survival
      in colorectal cancer (p=0.012).

PMID- 21870335
TI  - Increased migration of IgA lymphocytes to VIP nerve fibers after DSS-induced
      colitis.
AB  - Immunoglobulin-positive lymphocytes are present close to vasoactive intestinal
      polypeptide-positive (VIP(+)) nerve fibers in the lamina propria of the
      intestinal tract, and have an important role in mucosal defense. The number of
      immunoglobulin A-positive (IgA(+)) cells close to the epithelial basement
      membrane and nerve fibers is increased by the administration of
      lipopolysaccharides, which induce IgA secretion into the intestinal lumen. The
      relationship between immunoglobulin-positive lymphocytes and the VIP(+) nerve
      fibers during inflammation, such as in inflammatory bowel disease, however, is
      not well known. The morphological relationship between immunoglobulin-positive
      cells and the basement membrane or the VIP(+) nerve fibers in the colon was
      examined using double immunofluorescent labeling in an inflammatory bowel disease
      mouse model created by oral administration of dextran sodium sulfate (DSS). DSS
      administration induced goblet cell loss, crypt loss, intestinal epithelium
      deformation and infiltration of inflammatory cells in the mucosa. In the colon,
      the number and percentage of IgA(+) lymphocytes close to the basement membrane
      and the VIP(+) nerve fibers in the lamina propria increased after DSS
      administration, in parallel with the pathologic progress in the inflamed tissue.
      On the other hand, the percentage of immunoglobulin G-positive (IgG(+))
      lymphocytes close to the basement membrane and the VIP(+) nerve fibers decreased,
      although the total number of IgG(+) lymphocytes in the lamina propria increased.
      We suggest that the immunoglobulin-producing lymphocytes and enteric nerve fibers
      in the colon normally have a close morphological relationship, and that this
      relationship is reinforced in a cell-specific manner during inflammation.

PMID- 21870336
TI  - Diagnostic markers for glioblastoma.
AB  - Glioblastoma (GBM) is the most malignant form of cerebral gliomas, and despite
      distinct progress in surgical resection, radiation and chemotherapy, the
      prognosis of patients with GBM is still very poor. In the past decades knowledge
      of genomics and proteomics and of diagnostic, prognostic, predictive and
      pharmakodynamic markers measured in cerebrospinal-fluid (CSF), serum, or tumor
      tissue biomarkers has improved. This review briefly compiles our concepts on
      diagnostic markers for GBM, focusing on the latest developments.

PMID- 21870337
TI  - Connexin 43: its regulatory role in testicular junction dynamics and
      spermatogenesis.
AB  - Spermatogenesis is an intensely regulated process of germ cell development which
      takes place in the seminiferous tubules of the testis. In addition to known
      endocrine and autocrine/paracrine signaling pathways, there is now strong
      evidence that direct intercellular communication via gap junction channels and
      their specific connexins represents an important mechanism in the regulation of
      spermatogenesis. Another possibility is that connexins may indirectly regulate
      the spermatogenic process through modulation of tight and adherens junction
      proteins, further main structural components of the Sertoli-Sertoli junctional
      complexes at the blood-testis barrier site. The present review is focused on
      connexin 43 and updates its possible roles and functions in testicular junction
      dynamics and in the initiation and maintenance of spermatogenesis. In addition,
      testicular phenotypes of recently generated (1) conventional connexin 43 knockout
      mice, (2) connexin 43 knockin mice and (3) transgenic mice exhibiting a cell
      specific (conditional) connexin 43 knockout will be discussed.

PMID- 21870338
TI  - Big roles of microRNAs in tumorigenesis and tumor development.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-protein-coding small RNAs that
      are evolutionarily conserved and widely distributed among species. Their major
      function is to negatively regulate target gene expression. A single miRNA can
      regulate multiple target genes, indicating that miRNAs may regulate multiple
      signaling pathways and participate in a variety of physiological and pathological
      processes. Currently, approximately 50% of identified human miRNA-coding genes
      are located at tumor-related fragile chromosome regions. Abnormal miRNA
      expression and/or mutations have been found in almost all types of malignancies.
      These abnormally expressed miRNAs play roles similar to tumor suppressor genes or
      oncogenes by regulating the expression and/or function of tumor-related genes.
      Therefore, miRNAs, miRNA target genes, and the genes regulating miRNAs form a
      regulatory network with miRNAs in the hub. This network plays a pivotal role in
      tumorigenesis and tumor development.

PMID- 21870339
TI  - Adhesion and osteogenic differentiation of human mesenchymal stem cells on
      titanium nanopores.
AB  - Titanium implants are widely used in orthopaedic and dental surgery. Surface
      properties play a major role in cell and tissue interactions. The adhesion and
      differentiation of mesenchymal stem cells were studied as a function of
      nanostructures. Titanium surfaces with nanopores 30, 150 and 300 nm in diameter
      were prepared by physical vapour deposition. PCR arrays indicated that the
      expression of integrins was modulated by the nanopore size. Human Mesenchymal
      Stem Cells (hMSCs) exhibited more branched cell morphology on Ti30 than on other
      surfaces. Ti30 and Ti150 induced osteoblastic differentiation while Ti300 had a
      limited effect. Overall, nanopores of 30 nm may promote early osteoblastic
      differentiation and, consequently, rapid osseointegration of titanium implants.

PMID- 21870340
TI  - Exercise-induced pulmonary hemorrhage in horses: the role of pulmonary veins.
AB  - While airway endoscopy and bronchoalveolar lavage are the methodsof choice for
      diagnosing exercise-induced pulmonary hemorrhage (EIPH), these techniques do not
      allow accurate evaluation of the severity of bleeding. EIPH pathology is
      characterized by occlusive remodeling of pulmonary veins. Affected veins have
      large collagen deposits in their walls, which reduces their lumens. In the
      caudodorsal regions, pulmonary vein wall remodeling is associated with
      hemosiderin accumulation, bronchial circulation angiogenesis, and fibrosis of the
      alveolar interstitium, bronchovascular bundle, septa, and pleura. During
      exercise, venous occlusion increases regional pulmonary capillary pressure,
      likely causing capillary rupture and resulting in bleeding.

PMID- 21870341
TI  - Lung lobe torsion.
AB  - Lung lobe torsion is a rare pulmonary disorder in small animals and in humans.
      Torsion occurs when the lung lobe rotates around the bronchus and vascular supply
      and remains in that position. Lung lobe torsion is a life-threatening condition.
      The patient may present in an acute, fulminant respiratory crisis; however, more
      subtle clinical signs have also been reported. Lung lobe torsion may be secondary
      to an underlying pathology or spontaneous and idiopathic. Surgical resection of
      the affected lung lobe is the treatment of choice. The prognosis depends on the
      underlying cause. This article reviews the incidence, pathophysiology, clinical
      signs, diagnostic approach, and treatment of lung lobe torsion in dogs and cats.

PMID- 21870342
TI  - The equine pastern.
AB  - Injuries involving the pastern region are a common source of lameness in many
      types of performance horses. Knowledge of the common breed- and activity
      associated injuries can aid veterinarians in making an accurate diagnosis because
      injuries of the pastern region are often breed- or use-specific. The differential
      diagnosis for disorders of the pastern region includes osteoarthritis,
      osteochondrosis, fractures, infection, and soft tissue injuries. In general, soft
      tissue injuries of the pastern region can be difficult to diagnose, and affected
      horses have a reasonable chance of returning to their intended uses; osseous
      injuries are typically easier to diagnose and have a good prognosis if
      arthrodesis is an option.

PMID- 21870343
TI  - Blastomycosis.
AB  - For more than 100 years, blastomycosis has been recognized as causing significant
      morbidity and mortality in people and dogs. The disease is rare in cats.
      Isolation of the organism is difficult, and novel methods to culture
      environmental samples are forthcoming. The most significant clinical dilemma is
      the inability to make a timely diagnosis when multiple cytologic samples are
      unrewarding. This article reviews the literature on advances in epidemiology and
      serology, clinical presentations, new antifungal drugs, and progress in
      formulating a vaccine.

PMID- 21870344
TI  - The link between inflammation and coagulation: influence on the interpretation of
      diagnostic laboratory tests.
AB  - This article provides an overview of the complex relationship between
      inflammation and coagulation and a review of routinely available laboratory and
      point-of-care tests for the detection of inflammation and coagulopathies. In the
      management of cases requiring ongoing laboratory and clinical evaluation,
      examination of these two major pathologic processes may assist with diagnosis and
      improve outcome. Early identification of a pathologic inflammatory process may
      allow prevention of its progression to syndromes carrying a poorer prognosis,
      such as disseminated intravascular coagulation and multiple organ dysfunction
      syndrome.

PMID- 21870345
TI  - Paranasal sinus disease in horses.
AB  - The paranasal sinus system of horses is complex, comprising six pairs of sinuses.
      Disease processes that can develop in the sinuses include ethmoid hematomas,
      cysts, neoplasia, and bacterial and fungal infections. Horses that develop
      paranasal sinus disease vary widely in age. A significant number of clinical
      conditions involving the paranasal sinuses require a combination of diagnostic
      tests to determine the specific pathologic process. Because of the anatomic
      location of the paranasal sinuses and associated chronic conditions that affect
      many patients, many disease processes involving the paranasal sinuses require
      surgical correction for a favorable prognosis. Fungal and neoplastic processes of
      the equine paranasal sinuses have a less favorable prognosis than bacterial and
      other disease processes.

PMID- 21870346
TI  - Artificial insemination and embryo transfer in mares.
AB  - Mares can be artificially inseminated with chilled or frozen semen to increase
      the revenue from their offspring. Embryo transfer can be used to produce more
      than one foal from a single mare per season. Recent advances in using equine
      follicle-stimulating hormone to induce superovulation in mares have stimulated
      research on preserving equine embryos. Equine embryos are usually collected on
      day 7 or 8 after ovulation, and younger (day 6.5) embryos are typically
      cryopreserved. Cryopreservation improves the ability of veterinary clinicians to
      preserve embryos for implantation in recipient mares and facilitates
      international exchange of embryos.

PMID- 21870347
TI  - Hypertonic saline solutions in shock resuscitation.
AB  - Hypertonic saline solutions (HSS) have several characteristics that may improve
      the survival of patients during the initial treatment of certain types of shock.
      The use of isotonic crystalloids for resuscitation has several limitations: large
      infusion volumes are needed to increase the intravascular space; these large
      volumes cannot be given rapidly; and the fluid rapidly redistributes throughout
      the extravascular space. HSS are administered as a small-volume bolus over a few
      minutes and, by mobilizing extravascular water to the intravascular space, result
      in an immediate restoration of intravascular volume that can last several hours.
      Additional properties of HSS include positive effects on cardiac function, the
      microvasculature, and the immune system that not only justify their use in shock
      resuscitation but also suggest the opportunity for other applications.

PMID- 21870348
TI  - Streptococcus equi subspecies equi infection (strangles) in horses.
AB  - Streptococcus equi subspecies equi (strangles) is a highly contagious upper
      respiratory infection in horses. The infection is transmitted by inhalation or
      direct contact with mucopurulent discharge from an infective animal, resulting in
      fever, depression, and submandibular and retropharyngeal lymph node enlargement
      that can lead to respiratory distress. Complications include purpura hemorrhagica
      and metastatic abscessation. Control of outbreaks requires strict isolation
      protocols and hygiene measures. Detection of carriers is essential for preventing
      disease recurrence on a farm.

PMID- 21870349
TI  - Histoplasmosis.
AB  - Histoplasmosis is the most commonly diagnosed major systemic mycosis in dogs and
      the second most commonly reported fungal infection in cats. The causative
      organism, Histoplasma capsulatum, is endemic in 31 of the 48 contiguous US states
      and has a worldwide distribution. Histoplasma organisms enter the body via
      inhalation or, possibly, ingestion. They are phagocytized by macrophages and can
      be disseminated via the bloodstream or lymphatic system to the
      reticuloendothelial and gastrointestinal (GI) systems and, sometimes, the bones,
      skin, eyes, or brain. Clinical signs are often nonspecific, including lethargy,
      weight loss, and inappetence, although respiratory or GI signs may help localize
      the infection. Definitive diagnosis requires identification of H. capsulatum on
      cytology or histopathology. However, antigen testing may be useful in animals in
      the future. Itraconazole is the treatment of choice. The prognosis is fair for
      animals with pulmonary histoplasmosis and guarded to poor for those with GI or
      disseminated disease.

PMID- 21870350
TI  - Surgical sponges in small animal surgery.
AB  - Sponges are commonly used in veterinary practice. Uses for sponges in the
      operative arena include hemostasis, retraction, protection, dissection, and
      general wound management. Blood loss can be quantitated by counting blood-soaked
      sponges. Complications may arise when sponges are retained in the patient. Sponge
      retention is a risk whenever sponges are used during surgery, regardless of
      surgical procedure. This article reviews physical characteristics and proper uses
      of sponges, complications of sponge retention, and techniques to avoid retained
      sponges.

PMID- 21870351
TI  - Equine recurrent uveitis: classification, etiology, and pathogenesis.
AB  - Equine recurrent uveitis is a cyclical disease that affects the eye and often
      leads to high management costs and unfavorable results, such as blindness.
      Research has improved understanding of the roles of various etiologies,
      especially leptospirosis, in initiating and perpetuating the pathogenesis of
      equine recurrent uveitis. Research has also led to the discovery that specific
      breeds and horses with specific coat color patterns may be predisposed to
      developing recurrent uveitis.

PMID- 21870352
TI  - Equine recurrent uveitis: treatment.
AB  - Equine recurrent uveitis has traditionally been treated with medical management
      to reduce ocular inflammation and control pain during a single episode. Newer
      management methods include surgical options such as cyclosporine implantation and
      vitrectomy. These methods were developed not only to control inflammation but
      also to eliminate the underlying cause of uveitis in order to prevent recurrence.

PMID- 21870353
TI  - Canine brachycephalic airway syndrome: pathophysiology, diagnosis, and
      nonsurgical management.
AB  - Canine brachycephalic airway syndrome is a progressive disease that affects many
      brachycephalic dogs. This article describes the components of this syndrome and
      focuses on acute emergency management and long-term conservative management of
      these patients. Surgical management is described in a companion article.

PMID- 21870354
TI  - Canine brachycephalic airway syndrome: surgical management.
AB  - Many surgical options have been described to treat various aspects of canine
      brachycephalic airway syndrome (BAS). This article describes the surgical
      management, postoperative care, and prognosis of this condition. The
      pathophysiology and medical therapy of BAS are described in a companion article.

PMID- 21870356
TI  - The British College of Integrative Medicine (BCIM): two years on.

PMID- 21870355
TI  - Genetic diversity of Borrelia burgdorferi sensu lato isolates from Northeastern
      China.
AB  - Thirty-two strains of Borrelia burgdorferi sensu lato were isolated from Ixodes
      persulcatus ticks collected from northeastern China from May to June in 2004 and
      2005. Restriction fragment length polymorphism (RFLP) analysis and sequence
      analysis of 5S-23S rRNA intergenic spacer revealed that 29 (90.6%) belonged to
      Borrelia garinii, demonstrating B, C, and a unique pattern. The remaining three
      isolates (9.4%) were Borrelia afzelii with pattern D. The phylogenetic analysis
      based on 5S-23S rRNA intergenic spacer showed that B. garinii and B. afzelii
      genospecies clustered into two separate lineages. B. garinii strains were
      classified into three different branches: All the strains with RFLP pattern C
      were in the same branch, strain VH10 with a unique RFLP pattern clustered with
      strains VH9 and MDH2 with pattern B, and the rest of the strains with pattern B
      constitute another branch. These findings demonstrate the genetic diversity of B.
      burgdorferi sensu lato isolates from northeastern China.

PMID- 21870357
TI  - Commercial space flight: Scientists in space.

PMID- 21870358
TI  - Cases of bacterial pneumonia in cattle and sheep.

PMID- 21870359
TI  - Retraction notice to "Statin blocks Rho/Rho-kinase signalling and disrupts the
      actin cytoskeleton: relationship to enhancement of LPS-mediated nitric oxide
      synthesis in vascular smooth muscle cells" [Biochem.Biophys.Acta 1689(2004)267
      72].

PMID- 21870360
TI  - SOGC clinical practice guidelines: Substance use in pregnancy: no. 256, April
      2011.
AB  - OBJECTIVE: To improve awareness and knowledge of problematic substance use in
      pregnancy and to provide evidence-based recommendations for the management of
      this challenging clinical issue for all health care providers. OPTIONS: This
      guideline reviews the use of screening tools, general approach to care, and
      recommendations for clinical management of problematic substance use in
      pregnancy. OUTCOMES: Evidence-based recommendations for screening and management
      of problematic substance use during pregnancy and lactation. EVIDENCE: Medline,
      PubMed, CINAHL, and The Cochrane Library were searched for articles published
      from 1950 using the following key words: substance-related disorders, mass
      screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis,
      methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines.
      Results were initially restricted to systematic reviews and randomized control
      trials/controlled clinical trials. A subsequent search for observational studies
      was also conducted because there are few RCTs in this field of study. Articles
      were restricted to human studies published in English. Additional articles were
      located by hand searching through article reference lists. Searches were updated
      on a regular basis and incorporated in the guideline up to December 2009. Grey
      (unpublished) literature was also identified through searching the websites of
      health technology assessment and health technology assessment-related agencies,
      clinical practice guideline collections, clinical trial registries, and national
      and international medical specialty societies. VALUES: The quality of evidence
      was rated using the criteria described in the Report of the Canadian Task Force
      on the Preventive Health Care. Recommendations for practice were ranked according
      to the method described in that report (Table 1). BENEFITS, HARMS, AND COSTS:
      This guideline is intended to increase the knowledge and comfort level of health
      care providers caring for pregnant women who have substance use disorders.
      Improved access to health care and assistance with appropriate addiction care
      leads to reduced health care costs and decreased maternal and neonatal morbidity
      and mortality.

PMID- 21870361
TI  - [Autophagy: a necessary allied in the growth of pancreatic adenocarcinoma].

PMID- 21870362
TI  - Giant cell arteritis.

PMID- 21870363
TI  - [Stimulative role of corticotropin-releasing factor in methamphetamine-seeking
      behavior induced by footshock].

PMID- 21870364
TI  - [Suppressive effect of valproic acid on fear conditioning induced by dopamine in
      the amygdala: Its verification using the microdialysis].

PMID- 21870365
TI  - [Antidepressive effect of sodium butyrate and its effect on gene expression in
      rat hippocampus].

PMID- 21870366
TI  - [Influence of COMT Val 158 met gene polymorphism on human frontal lobe
      controlling impulsivity].

PMID- 21870367
TI  - [Relationship between Oprm1 polymorphism and morphine sensitivity in inbred
      strain mice derived from wild mice].

PMID- 21870368
TI  - [Role of glutamine transporter expressed in astroglia cells in glutamic acid
      induced neuronal death].

PMID- 21870369
TI  - [Stimulative effect of edaravone on growth of neuronal stem cells and precursor
      cells following lesioning of hippocampal dentate gyrus].

PMID- 21870370
TI  - Analysis of plastic deformation in cortical bone after insertion of coated and
      non-coated self-tapping orthopaedic screws.
AB  - Insertion of internal fracture fixation devices, such as screws, mechanically
      weakens the bone. Diamond-like carbon has outstanding tribology properties which
      may decrease the amount of damage in tissue. The purpose of this study was to
      investigate methods for quantification of cortical bone damage after orthopaedic
      bone screw insertion and to evaluate the effect of surface modification on tissue
      damage. In total, 48 stainless steel screws were inserted into cadaver bones.
      Half of the screws were coated with a smooth amorphous diamond coating.
      Geometrical data of the bones was determined by peripheral quantitative computed
      tomography. Thin sections of the bone samples were prepared after screw
      insertion, and histomorphometric evaluation of damage was performed on images
      obtained using light microscopy. Micro-computed tomography and scanning electron
      microscopy were also used to examine tissue damage. A positive correlation was
      found between tissue damage and the geometric properties of the bone. The age of
      the cadaver significantly affected the bone mineral density, as well as the
      damage perimeter and diameter of the screw hole. However, the expected positive
      effect of surface modification was probably obscured by large variations in the
      results and, thus, statistically significant differences were not found in this
      study. This can be explained by natural variability in bone tissue, which also
      made automated image analysis difficult.

PMID- 21870371
TI  - Design of a novel, one-sided, pedal-activated wheelchair.
AB  - The present paper proposes the design of a novel, one-sided, pedal-activated
      wheelchair for patients with hemiplegia or hemiparesis. The design comprises a
      planetary hub transmission, which is embedded in the hub of the wheelchair, with
      drive, neutral, and reverse modes. The paper first discusses the structural
      characteristics and motion transmission of the wheelchair, and then presents the
      motion design of the hub transmission, followed by assembly and testing of the
      prototype. The results confirm that the proposed wheelchair and hub transmission
      can meet users' demands, thus improving comfort and independence.

PMID- 21870372
TI  - A simple, economical, and effective portable paediatric mock circulatory system.
AB  - Ventricular assist devices (VADs) and total artificial hearts have been in
      development for the last 50 years. Since their inception, simulators of the
      circulation with different degrees of complexity have been produced to test these
      devices in vitro. Currently, a new path has been taken with the extensive efforts
      to develop paediatric VADs, which require totally different design constraints.
      This paper presents the manufacturing details of an economical simulator of the
      systemic paediatric circulation. This simulator allows the insertion of a
      paediatric VAD, includes a pumping ventricle, and is adjustable within the
      paediatric range. Rather than focusing on complexity and physiological
      simulation, this simulator is designed to be simple and practical for rapid
      device testing. The simulator was instrumented with medical sensors and data were
      acquired under different conditions with and without the new PediaFlowTM
      paediatric VAD. The VAD was run at different impeller speeds while simulator
      settings such as vascular resistance and stroke volume were varied. The hydraulic
      performance of the VAD under pulsatile conditions could be characterized and the
      magnetic suspension could be tested via manipulations such as cannula clamping.
      This compact mock loop has proven to be valuable throughout the PediaFlow
      development process and has the advantage that it is uncomplicated and can be
      manufactured cheaply. It can be produced by several research groups and the
      results of different VADs can then be compared easily.

PMID- 21870373
TI  - A study on optimal bonding angles of bi-material interfaces in dental crowns with
      porcelain fused to metal.
AB  - Interfaces between two different materials exist in the dental crowns used in
      dental restoration work. A common failure mode observed in dental crowns is
      debonding/fracture that is initiated at the corners of the interface between two
      materials, where a stress concentration or a stress singularity can be created.
      In this paper, finite element modelling and analytical methods are used to
      analyse the stress singularity at the free edge corners at the interfaces between
      porcelain and metal and also metal and cement in porcelain-fused-to-metal (PFM)
      crowns. Optimal ranges of bonding angles at the corners of the interface, that
      result in the elimination of the stress singularity, are obtained for PFM crowns
      made from a precious-metal-based or non-precious-metal-based alloy, respectively.
      The findings presented in this paper can serve as guidelines for the design and
      manufacture of PFM dental crowns.

PMID- 21870374
TI  - Computation of bone remodelling after Duracon knee arthroplasty using a
      thermodynamic-based model.
AB  - The present study utilizes a recently developed literature model for the bone
      remodelling process to predict the evolution of bone density following Duracon
      total knee arthroplasty (TKA). In this model, which is based on chemical kinetics
      and irreversible thermodynamics, bone is treated as a self-organizing system
      capable of exchanging matter, energy, and entropy with its surroundings. Unlike
      previous models in which mechanical loading is regarded as the only stimulus for
      bone remodelling, the present model establishes a unique coupling between
      mechanical loading and the chemical reactions involved in the process of bone
      remodelling. This model was incorporated into the finite element software ANSYS
      by means of a macro to compute density distribution in distal femoral bone both
      before and after TKA. Consistent with dual-energy X-ray absorptiometry (DEXA)
      scans reported in the literature, the results showed that the most severe bone
      loss occurs in the anterior region of the distal femur and that there is more
      bone resorption in the lateral than the medial condyle following TKA.
      Furthermore, the bone density distribution predicted using the present model
      showed a gradual and uniform pattern and thus a more realistic bone evolution
      contrary to the strain energy density model, where there is no gradual bone
      density evolution.

PMID- 21870375
TI  - Immunohistochemical analysis of structural changes in collagen for the assessment
      of osteoarthritis.
AB  - Collagen fibrillation within articular cartilage (AC) plays a key role in joint
      osteoarthritis (OA) progression and, therefore, studying collagen synthesis
      changes could be an indicator for use in the assessment of OA. Various staining
      techniques have been developed and used to determine the collagen network
      transformation under microscopy. However, because collagen and proteoglycan
      coexist and have the same index of refraction, conventional methods for specific
      visualization of collagen tissue is difficult. This study aimed to develop an
      advanced staining technique to distinguish collagen from proteoglycan and to
      determine its evolution in relation to OA progression using optical and laser
      scanning confocal microscopy (LSCM). A number of AC samples were obtained from
      sheep joints, including both healthy and abnormal joints with OA grades 1 to 3.
      The samples were stained using two different trichrome methods and
      immunohistochemistry (IHC) to stain both colourimetrically and with fluorescence.
      Using optical microscopy and LSCM, the present authors demonstrated that the IHC
      technique stains collagens only, allowing the collagen network to be separated
      and directly investigated. Fluorescently-stained IHC samples were also subjected
      to LSCM to obtain three-dimensional images of the collagen fibres. Changes in the
      collagen fibres were then correlated with the grade of OA in tissue. This study
      is the first to successfully utilize the IHC staining technique in conjunction
      with laser scanning confocal microscopy. This is a valuable tool for assessing
      changes to articular cartilage in OA.

PMID- 21870376
TI  - Pressure waves in the aorta during isolated abdominal belt loading: the
      magnitude, phasing, and attenuation.
AB  - While rupture of the aorta is a leading cause of sudden death following motor
      vehicle crashes, the specific mechanism that causes this injury is not currently
      well understood. Aortic ruptures occurring in the field are likely due to a
      complex combination of contributing factors such as acceleration, compression of
      the chest, and increased pressure within the aorta. The objective of the current
      study was to investigate one of these factors in more detail than has been done
      previously; specifically, to investigate the in situ intra-aortic pressure
      generated during isolated belt loading to the abdomen. Ten juvenile swine were
      subjected to dynamic belt loads applied to the abdomen. Intraaortic pressure was
      measured at multiple locations to assess the magnitude and propagation of the
      resulting blood pressure wave. The greatest average peak pressure (113.6 +/- 43.5
      kPa) was measured in the abdominal aorta. Pressures measured in the thoracic
      aorta and aortic arch were 70 per cent and 50 per cent, respectively, that
      measured in the abdominal aorta. No macroscopic aortic trauma was observed. To
      the authors' knowledge the present study is the first one to document the
      presence, propagation, and attenuation of a transient pressure wave in the aorta
      generated by abdominal belt loading. The superiorly moving wave is sufficient to
      generate hydrostatic and intimal shear stress in the aorta, possibly contributing
      to the hypothesized mechanisms of traumatic aortic rupture.

PMID- 21870377
TI  - Inlet protein aggregation: a new mechanism for lubricating film formation with
      model synovial fluids.
AB  - This paper reports a fundamental study of lubricant film formation with model
      synovial fluid components (proteins) and bovine serum (BS). The objective was to
      investigate the role of proteins in the lubrication process. Film thickness was
      measured by optical interferometry in a ball-on-disc device (mean speed range of
      2-60 mm/s). A commercial cobalt-chromium (CoCrMo) metal femoral head was used as
      the stationary component. The results for BS showed complex time-dependent
      behaviour, which was not representative of a simple fluid. After a few minutes
      sliding BS formed a thin adherent film of 10-20 nm, which was attributed to
      protein absorbance at the surface. This layer was augmented by a hydrodynamic
      film, which often increased at slow speeds. At the end of the test deposited
      surface layers of 20-50 nm were measured. Imaging of the contact showed that at
      slow speeds an apparent 'phase boundary' formed in the inlet just in front of the
      Hertzian zone. This was associated with the formation of a reservoir of high
      viscosity material that periodically moved through the contact forming a much
      thicker film. The study shows that proteins play an important role in the film
      forming process and current lubrication models do not capture these mechanisms.

PMID- 21870378
TI  - Salvage procedures for trochanteric femoral fractures after internal fixation
      failure: biomechanical comparison of a plate fixator and the dynamic condylar
      screw.
AB  - The aim of this study was the biomechanical evaluation of the reversed less
      invasive stabilization system (LISS) internal fixation as a joint-preserving
      salvage procedure for trochanteric fractures. Five LISS plates and five dynamic
      condylar screws (DCS) were tested using synthetic femora (Sawbones) with an
      osteotomy model similar to a type-A2.3 pertrochanteric fracture. The constructs
      were subjected to axial loading up to 1000 N for five cycles. Then, the force was
      continuously increased until fixation failure. For the evaluation of the
      biomechanical behaviour, the stiffness levels were recorded and the osteotomy gap
      displacement was mapped three-dimensionally. The average stiffness for the
      constructs with LISS plates was 412 N/mm (with a standard deviation (SD) of
      103N/mm) and 572N/mm (SD of 116 N/mm) for the DCS constructs (p=0.051). Local
      displacement at the osteotomy gap did not yield any significant differences. The
      LISS constructs failed at a mean axial compression of 2103N (SD of 519N) and the
      DCS constructs at a mean of 2572N (SD of 372N) (p=0.14). It is concluded that the
      LISS plate offers a reliable fixation alternative for salvage procedures.

PMID- 21870379
TI  - Nanocomposite biomaterial mimicking aortic heart valve leaflet mechanical
      behaviour.
AB  - The main problem with polymeric heart valves (which are already biocompatible) is
      that they usually fail in the long term owing to tearing and calcification of the
      leaflets under high dynamic tensile bending stress and oxidative reactions with
      blood. To overcome this shortcoming, it is hypothesized that synthetic valve
      leaflets which mimic native valve leaflet structure fabricated from fibre
      reinforced composite material will optimize leaflet stresses and decrease tears
      and perforations. The objective of this study is to develop a PVA-BC (polyvinyl
      alcohol-bacterial cellulose)-based hydrogel that mimics not only the non-linear
      mechanical properties displayed by porcine heart valves, but also their
      anisotropic behaviour. By applying a controlled strain to the PVA samples, while
      undergoing low-temperature thermal cycling, it was possible to create oriented
      mechanical properties in PVA hydrogels. The oriented stress-strain properties of
      porcine aortic valves were matched simultaneously by a PVA hydrogel (15 per cent
      PVA, 0.5 BC cycle 4, 75 per cent initial tensile strain). This novel technique
      allows the control of anisotropy to PVA hydrogel, and gives a broad range of
      control of its mechanical properties, for specific medical device applications.

PMID- 21870380
TI  - The scope of emergency mental health services.

PMID- 21870381
TI  - Helping military children cope with parental deployment: role of attachment
      theory and recommendations for mental health clinicians and counselors.
AB  - Military deployment of a parent carries with it a number of stresses for
      children, all centering around uncertainty, instability and unpredictability.
      This article conceptualizes military deployment and relocation stress in the
      context of attachment theory, and describes the types of adverse outcomes that
      can occur as the result of impaired attachment. It then presents a set of
      practical recommendations for mental health clinicians and counselors for helping
      children and families cope productively and negotiate the developmental hurdles
      associated with maintaining healthy attachment and family stability in the face
      of military deployment.

PMID- 21870382
TI  - The use of psychosocial assessment following the Haiti earthquake in the
      development of the three-year emotional psycho-medical mental health and
      psychosocial support (EP-MMHPS) plan.
AB  - This article provides information about the 2010 Haiti earthquake. An assessment
      model used by a crisis counselor responding to the earthquake is presented,
      focusing on the importance of gathering pre-deployment assessment and in-country
      assessment. Examples of the information gathered through the in-country
      assessment model from children, adolescents, and adults are presented. A brief
      overview of Haiti's three-year Emergency Psycho-Medical Mental Health and
      Psychosocial Support (EP-MMHPS) is provided. Finally, how the psychosocial manual
      developed after assessing 200 Haitian survivors through in-country assessment,
      and information gathered through pre-deployment assessment became part of the EP
      MMHPS is offered.

PMID- 21870383
TI  - The parent-rated social skills of a sample of New York City preschool children 8
      10 months after September 11, 2001.
AB  - This study compared the Social Skills Rating System-Preschool Parent Version
      ratings of two groups of New York City preschool children 8-10 months after
      September 11, 2001. One group of children was within 1 mile (1.61 km) of the
      World Trade Center (WTC) during the attack and exposed to one or more traumatic
      events. The second group was 2.04 to 14 miles (3.28-22.54 km) away from the WTC
      and not exposed to traumatic events. The social skills ratings of the comparison
      groups did not significantly differ These outcomes were consistent after
      statistically adjusting for the potentially confounding influence of parental
      PTSD, anxiety, and depression symptoms.

PMID- 21870384
TI  - Differences in compassion fatigue, symptoms of posttraumatic stress disorder and
      relationship satisfaction, including sexual desire and functioning, between male
      and female detectives who investigate sexual offenses against children: a pilot
      study.
AB  - Law enforcement detectives who work with traumatized individuals, especially
      children who were victims of sexual abuse or assault, are likely to experience
      job-related emotional distress. The purpose of this study was to examine the
      relations among compassion fatigue, probable PTSD symptoms, and personal
      relationship satisfaction, including communication and sexual satisfaction, in a
      sample of 47 male and female detectives. Responses to the administered
      questionnaires indicated a relation between compassion fatigue symptoms and
      probable PTSD symptoms. There also were compelling gender differences. For
      example, for male detectives, open communication with their spouse or significant
      other was negatively correlated with burnout, indicating the more open the
      communication, the lower the reported burnout. However for female detectives
      there was a negative correlation between open communication with spouse or
      significant other and compassion satisfaction, suggesting that more open
      communication was related to lower levels of satisfaction with their ability to
      be a professional caregiver Furthermore, although stepwise regression analysis
      indicated that years of service as a detective is independently associated with
      sexual desire, female detectives evidenced less sexual desire and more difficulty
      with sexual functioning than did male detectives. Implications of these
      preliminary findings are discussed and limitations addressed.

PMID- 21870385
TI  - Time of psychiatric patient assaults: twenty-year analysis of the Assaulted Staff
      Action Program (ASAP).
AB  - Apparent random acts of violence viewed in the aggregate appear to occur in
      fairly exacting temporal patterns. This is true of rape, street assaults, and
      domestic violence, among other acts of violence. Patient assaults on staff as
      acts of violence should also follow a temporal pattern. This twenty-year
      retrospective study of assaultive psychiatric patients in one public sector
      examined the temporal pattern of such assaults. Inpatient assaults were more
      likely to occur in the summer in the middle ten days of the month, during the
      first shift at mealtimes. In community settings, assaults were more likely in
      winter during the first ten days of the month, and on the first shift at noon
      time. The possible reasons for these time patterns, their possible biological
      roots, and their implications for emergency services personnel and health care
      providers were discussed.

PMID- 21870386
TI  - Managing problem employees: a model program and practical guide.
AB  - This article presents a model program for managing problem employees that
      includes a description ofthe basic types of problem employees and employee
      problems, as well as practical recommendations for. (1) selection and screening,
      (2) education and training, (3) coaching and counseling, (4) discipline, (5)
      psychological fitness-for-duty evaluations, (6) mental health services, (7)
      termination, and (8) leadership and administrative strategies. Throughout, the
      emphasis on balancing the need for order and productivity in the workplace with
      fairness and concern for employee health and well-being.

PMID- 21870387
TI  - [Analysis of pedicle screw misplacement in treating scoliosis using thoracic
      pedicle screw fixation].

PMID- 21870388
TI  - [Clinical study of posterior transarticular fixation with rod-screw in the lower
      cervical vertebrae].
AB  - OBJECTIVE: To explore the effects of posterior transarticular fixation with rod
      screw in treating fracture and dislocation, spinal stenosis of lower cervical
      vertebrae. METHODS: From July 2005 to July 2009,11 patients with cervical
      fracture and dislocation and 9 with spinal stenosis of lower cervical vertebrae
      underwent operation with transarticular fixation with rod-screw (Vertex system).
      There were 16 cases male and 4 cases female, ranging in age from 29 to 76 years
      with an average of 51 years. All patients underwent decompression,internal
      fixation and fusion through posterior approach (combined with anterior approach
      in 3 cases). The method of insertion of screw: the starting point located in
      medial 1 mm of the midpoint of the lateral mass, angle in sagittal plane was 15
      degrees-20 degrees of caudal clinism and in coronal plane was 35 degrees-40
      degrees of external clinism. The position of screws, the cervical array, bone
      graft and fusion were observed by X-ray films. RESULTS: A total of 88
      transarticular screws were successfully inserted, 10 screws located in C3,4, 20
      in C4,5, 32 in C5,6, 26 in C6,7. There were no complications related to screw
      insertion, such as injury of the vertebral artery, nerve roots and the spine
      cord. All patients obtained bone fusion without internal fixation breaking. The
      improvement rate of JOA was 55.8% at the 1st week after operation, 5 cases got
      excellent results, 7 good, 7 fair, 1 poor; the improvement rate of JOA was 74.5%,
      at the 3rd month after operation, 6 cases got excellent results, 8 good, 6 fair.
      There was significant difference in the JOA between before operation and at the
      3rd month after operation. CONCLUSION: The transarticular screw fixation with rod
      screw in the lower cervical spine is an effective fixation, which has advantages
      of rigid stability, convenience to perform, and can reduce operative risk in
      initial application, but the long-term follow-up is very necessary.

PMID- 21870389
TI  - [Treatment of thoracalumbar fractures with pedicle-screw placement on the level
      of injured vertebrae].
AB  - OBJECTIVE: To investigate the clinical results of pedicle-screw placement and
      reduction on the level of injured vertebrae in treating thoracolumbar fractures.
      METHODS: From March 2006 to May 2009, 27 patients with thoracolumbar fractures
      were treated with short-segment fixation system and pedicle-screw placement on
      injured vertebrae through posterior approach. There were 19 males and 8 females
      with an average age of 36 years old ranging from 24 to 68 years. Eleven patients
      were injuried by traffic accident, 9 patients were injuried by falling from high,
      5 patients were injuried by crush from weighty object, 2 patients were others
      injuries. Thoracolumbar fractures were classified according to Gertibein
      classification: 2 cases were of type A1, 3 cases A2, 12 cases A3, 5 cases B1, 5
      cases B2. Among them, 14 cases were accompanied with spinal cord
      injuries,functional assessment of nerves was assessed according to Frankel
      criteria: 5 cases were of grade B, 3 cases C, 6 cases D. Lumbago according to
      Denis standard, grade P5 was in all cases. The injured level of 5 cases was in
      T11, 11 cases in T12, 8 cases in L1, 3 cases in L2. From injury to operation it
      was 2-15 days with an average of 4 days. The ratio of vertebral height between
      anterior and posterior border, anteroposterior Cobb angle were compared before
      and after operation. Function of nerves and index of lumbago were evaluated by
      Frankel and Denis classification. RESULTS: All patients were followed up from 14
      to 17 months with the mean of 15.5 months. At final follow-up,according to
      Frankel score system to evaluate function of nerve,2 cases were of grade B, 4
      case grade C, 3 cases grade D, 5 cases grade E; according to Denis score system
      to evaluate index of lumbago, there was P1 (without pain) in 17 cases, P2
      (between whiles minute pain, need not treatment) in 8 cases, P3 (moderate pain,
      between whiles need medication) in 2 cases. The ratio of vertebral height between
      anterior and posterior border from preoperatively 0.32 +/- 0.14 to
      postoperatively 0.85 +/- 0.03 (P<0.01); anteroposterior Cobb angle from
      preoperatively (25.3 +/- 7.8) degrees to postoperatively (11.1 +/- 1.5) degrees
      (P<0.01). At final follow-up, the ratio of vertebral height between anterior and
      posterior border, anteroposterior Cobb angle were respectively 0.81 +/- 0.06 and
      (11.8 +/- 1.9) degrees, there was no significant difference between postoperative
      and at final follow-up (P>0.05). No complications such as infection, internal
      fixation failure,nerve injuries were found during follow-up. CONCLUSION:
      Posterior short-segment fixation system and pedicle-screw placement on level of
      injured vertebrae is one kind of effective method in treating thoracolumbar
      fracture, which can maintain corrective effect and obtain better clinical
      outcomes.

PMID- 21870390
TI  - [Expansive pedicle screws fixation combined with Wright artificial bone
      implantation for treatment of thoracolumbar burst fracture of the elderly
      patients].
AB  - OBJECTIVE: To observe the effects of expansive pedicle screws fixation combined
      Wright artificial bone implantation in treating thoracolumbar burst fracture of
      the elderly. METHODS: From March 2007 to July 2009, 12 patients with
      thoracolumbar burst fractures were treated with surgery in the study. There were
      7 males and 5 females, with an average age of 62.3 years (from 56 to 71 years).
      Nerve functions of all patients were ASIA classified grade E. According to TLICS
      score system, 6 points were in 5 cases and 7 points were in 7 cases. Expansive
      pedicle screw system was used and Wright artificial bone was injected into the
      injuried vertebrae. The anterior border height of vertebral body and Cobb angle
      were observed at the preoperation, postoperation and final follow-up. RESULTS:
      All patients were followed up from 10 to 15 months with an average of 12 months.
      Wounds healed well, pain in the chest-back abated, no the expansive pedicle
      screws loosened or broke down. The anterior border height of vertebral body
      increased from (32.3 +/- 9.1)% preoperatively to (95.3 +/- 3.2)% postoperatively;
      and the Cobb angle decreased from (31.6 +/- 6.8) degrees preoperatively to (4.5
      +/- 3.2) degrees postoperatively. There was significant difference between two
      groups (P<0.01). After 3 months, the anterior border height of vertebral body was
      (94.7 +/- 3.3)% and the Cobb angle was (4.6 +/- 3.4) degrees; at the final follow
      up, the anterior border height of vertebral body was (93.2 +/- 3.6)% and the Cobb
      angle was (5.3 +/- 3.7) degrees. There was no significant difference between the
      two data (P>0.05). CONCLUSION: The combination of expansive pedicle screws
      fixation and Wright artificial bone injection is a good treatment for
      thoracolumbar burst fracture, with advantages such as easy operation and good
      effect, which mainly applied to patients with no obvious nerve injuries.

PMID- 21870391
TI  - [Clinical study on surgical treatment for thoracolumbar burst fractures].
AB  - OBJECTIVE: To explore the choice of operative approach for thoracolumbar burst
      fractures and evaluate its clinical effects. METHODS: From September 2005 to
      March 2009, the clinical data of 94 patients with thoracolumbar burst fractures
      were analyzed retrospectively. Including 59 males and 35 femals with an average
      age of 36.8 years (ranged from 20 to 63). The fractures were classified according
      to Denis classification: 17 cases of type A, 32 cases of type B, 6 cases of type
      C, 24 cases of type D, 15 cases of type E. Neurological injuries were classified
      according to ASIA classification: 3 cases of grade A, 4 cases of type B, 23 cases
      of grade C, 38 cases of grade D, 26 cases of grade E. Among the patients, 42
      cases were treated with reduction, decompression, internal fixation with pedicle
      screw through posterior approach, meanwhile, of them, 18 cases with posterior
      lateral bone graft fusion; 36 cases were treated with decompression, bone graft,
      through anterior approach, of them, 16 cases with TSRH system fixation and 20
      cases with Zeplate system fixation; 16 cases (because of bone block intruded into
      vertebral canal leading to spinal cord compression ) were treated with anterior
      and posterior approach, internal fixation with pedicle-screw through posterior
      approach and subtotal vertebrectomy, decompression, titanium mesh cages bone
      graft fusion through anterior approach, meanwhile, of them, 8 cases with screw
      rod and titanium steel plate system fixation. RESULTS: All patients obtained good
      results and were followed up from 9 to 52 months with an average of 22.8 months.
      Cobb angle were corrected from preoperatively (25.00 +/- 5.50) degrees to
      postoperatively (4.20 +/- 1.80) degrees. Height of anterior and posterior border
      of vertebral body improved from preoperatively (50.80 +/- 2.82)%, (79.30 +/-
      3.08)% to postoperatively (94.85 +/- 1.80)%, (98.20 +/- 1.40)%, respectively. The
      ratio of protruded bones to the spinal canal anteroposterior diameter decreased
      from preoperatively (33.10 +/- 1.40)% to postoperatively (6.70 +/- 1.50)%.
      Sagittal abnormity were corrected; posterior convex angle and height were no
      markedly lost during follow-up; no internal fixation loosening and titanium mesh
      displacement were found. In the aspect of never function, except for 1 case of
      grade A there is no recovered others obtained different improvement, among them,
      from grade A to B was in 2 cases; B to C, D was in 2,2, respectively; C to D, E
      was 16,7, respectively; D to E was in 38 cases. CONCLUSION: The two factors
      decide surgical methods:the integrity of posterior ligamentous complex and
      nervous system function. Anterior approach refers to patients with incomplete
      spinal cord injury and anterior vertebral canal compression; posterior approach
      refers to patients with injury of posterior ligamentous complex; combination with
      anterior and posterior approach refers to patients with two injury factors.

PMID- 21870392
TI  - [Treatment of thoracolumbar burst fracture with subtotal vertebrectomy,
      decompression and strut grafting through posterolateral approach].
AB  - OBJECTIVE: To explore the clinical effect of subtotal vertebrectomy,
      decompression and strut grafting in treating thoracolumbar burst fractures
      through posterolateral approach via posterior midline incision. METHODS: From May
      2005 to July 2008, 14 patients with thoracolumbar burst fractures were treated
      with subtotal vertebrectomy, decompression and strut grafting through
      posterolateral approach via posterior midline incision. There were 9 males and 5
      females, ranging in age from 24 to 68 years, with an average of 42.3 years. All
      patients were single segment fractures, of them, T11 was in 1 case, T12 in 5, L1
      in 5 and L2 in 3. According to AO classification in spinal fracture, type A3 was
      in 5 cases, B1 in 3, B2 in 3, C1 in 2, C2 in 1. According to the ASIA
      classification in neurological function, grade A was in 3 cases, B in 3, C in 5,
      D in 2, E in 1. The height of anterior border vertebral body, volume of spinal
      canal and neurological function were analyzed by X-ray films, CT scanning and
      ASIA classification preoperative, postoperative and at final follow-up. RESULTS:
      Operative time was from 3.5 to 5.5 hours with the mean of 4.0 hours; bleeding
      during operation was from 800 to 2 600 ml with the mean of 1 300 ml. Two cases
      with nerve root injury recovered without special handling after 3-6 months; 1
      case with leakage of cerebrospinal fluid restored through lumbar cerebrospinal
      fluid drainage; 1 case with pleura tear healed through closed thoracic drainage.
      No iatrogenic vascular injury or infection was found. The follow-up time was from
      8 to 36 months with the mean of 16.5 months. All patients had neurofunctional
      recovery at different degree, except that 3 patients in grade A. The height of
      anterior border vetebral body restored from (42.25 +/- 11.87)% preoperatively to
      (94.38 +/- 3.08)% postoperatively, and (92.87 +/- 3.32)% at final follow-up
      (P<0.05); volume of spinal canal (the actual volume of spinal canal/normal volume
      of spine canal) increased from (45.63 +/- 6.88)% preoperatively to (95.26 +/-
      3.31)% postoperatively, and (96.13 +/- 2.56)% at final follow-up (P<0.05). Cobb
      angle were corrected from (25.64 +/- 4.40) degrees preoperatively to (5.80 +/-
      1.14) degrees postoperatively; Cobb angle lost from 0 degrees to 6 degrees at
      final follow-up with (8.10 +/- 2.65) degrees. All patients obtained complete bony
      fusion without pseudarthrosis formation at final follow-up. CONCLUSION: Subtotal
      vertebrectomy decompression and strut grafting through posterolateral approach
      via posterior midline incision is an effective and safe method in treating
      thoracolumbar burst fracture, which can restored height of intervertebral body,
      volume of spinal canal and physiological flexion of spinal column, and retain
      spinal permanent stability.

PMID- 21870393
TI  - [Analysis of concurrent intravertebral vacuum sign in thoracolumbar fractures
      after posterior internal fixation].
AB  - OBJECTIVE: To investigate the importance of TLICS classification to surgical
      options of thoracolumbar fractures by analyzing the cause of intravertebral
      vacuum sign, vertebral collapse and vertebral pseudarthrosis. METHODS: From
      January 2006 to December 2010, the clinical data about 15 patients with
      postoperative complications by thoracolumbar fracture after posterior internal
      fixation were retrospectively analyzed. There were 9 males and 6 females, ranging
      in age from 18 to 75 years, with an average of 54.6 years. Of them, fracture site
      in T12 was 7 cases, L1 was 5 cases, L2 was 3 cases; compression fractures was in
      12 cases and burst fracture was in 3 cases; according to classification of TLICS,
      12 cases were of type I ,3 cases of type III. And the causes of complications
      after posterior fixation were analyzed according clinical manifestation and
      imaging finding combined with review literatures. RESULTS: After 10 to 20 months
      following-up (with average of 15 months), loss of vertebral height found in 9
      cases (4 cases existed vertebral collapse, as well as 3 cases occurred screw
      loosening) and Intravertebral Vacuum Sign appeared in 6 cases. CONCLUSION: In
      order to avoid the vertebral vacuum and fixation failure, the clinical data of
      patients should be roundly and carefully evaluated, surgical indications should
      be strictly controlled and the surgical approach should be selected according to
      correct classification. Particularly, the reconstruction of the stability of
      former spinal column shoud be paid more attention.

PMID- 21870394
TI  - [Anterior approach supporting bone graft for the treatment of old thoracolumbar
      fractures without neurological symptom].
AB  - OBJECTIVE: To retrospectively analyze the surgical effect of anterior approach
      bone graft and internal fixation methods for treating old thoracolumbar fracture
      without neurological symptom, so as to provide references for surgical treatment
      of such kind of fracture. METHODS: From April 2004 to April 2009, 22 cases of old
      thoracolumbar fractures were treated, including 15 males and 7 females with an
      average age of 38 years ranging from 21 to 56 years. The time from injured to
      operation was from 4 months to 2 years (average 8 months). Anterior approach
      surporting bone graft and internal fixation were performed. All patients were
      followed up for at least 12 months, the Cobb angle depending on lateral
      radiographs and VAS scores were compared between pre-operative and post
      operative. Complication was observed. RESULTS: The average preoperative Cobb
      angle of kyphosis was (15.0 +/- 2.4) degrees (8.0 degrees to 28.0 degrees), VAS
      score was 7.0 +/- 0.7. The average two weeks after operation was (3.0 +/- 1.6)
      degrees (-2.0 degrees to 9.0 degrees), VAS score was 1.0 +/- 0.6. The average
      Cobb angle at one year after operation was (3.5 +/- 1.4) degrees (0.0 degrees to
      12.0 degrees), VAS score was 1.2 +/- 0.6. There were statistically significant
      differences in the above indexes between preoperation and two weeks after
      operation (P<0.05), while no statistically significant difference was found
      between 2 weeks and 1 year after operation (P>0.05). Bony fusion were achieved in
      21 patients, nounion were occurred in 1 patient, but without correction loss.
      CONCLUSION: According to Cobb angle of kyphosis, anterior approach surporting
      bone graft and internal fixation is a reasonable strategy to treat old
      thoracolumbar fracture without neurological symptom.

PMID- 21870395
TI  - [Feasibility and clinical application of design about the hollowed titanium stick
      supporting the femoral head and preventing it from collapsing].
AB  - OBJECTIVE: To evaluate the feasibility and the clinical practicality of the
      design about the hollowed titanium stick supporting the femoral head and
      preventing it from collapsing. METHODS: From Jan.2003 to Jun.2007, 36 patients
      (46 hips) diagnosed as cystis degeneration of the femoral head were treated by
      surgical operation, including 20 males and 16 females with an average age of 40
      years ranging from 18 to 56 years old, and the course of the disease was from 10
      to 24 months (16 months on average). According to ARCO staging,there were 24
      patients (34 hips) in NFH II, of which 11 hips were II a stage, 13 hips were II b
      stage and 10 hips were II c stage; there were 6 patients diagnosed as
      osteofibrous,4 patients as simple bone cyst and 2 patients as chondromyxoid
      fibroma. Under X-ray the percutaneous narrow core decompression and focus
      infection elimination were performed and supported the sclerotin under the
      cartilage with titanium stick. The patients were followed-up at the first, third,
      sixth, twelfth, twenty-fourth and thirty-sixth month after the operation. The
      clinical evaluation was done by X-ray and the indexes included stable, unstable
      and abortive. The data was analyzed by Fisher exact probility and the suviaval
      rate was analyzed by Kaplan-Meier suviaval curve using statistical soft ware
      SPSS13.5. RESULTS: There were no unstable or failure cases on each period from
      the 1st month to the 12th month after the operation, indicating that the
      supporting effect of the titanium stick was exact during 12 months after the
      operation. There were unstable and failure cases from the 12th month to the 24th
      month after the operation, which were mainly in stage NFH II c but the
      comparision of the stable rate in this period and 12 months after the operation
      had no obvious statistical differences (P>0.05) indicating that the supporting
      effect of the titanium stick was feasible during the stage. One of the unstable
      cases deteriorated and failed but there were no new unstable cases, both the
      stable rate and the unstable rate had no change and the failure rate rose on the
      36th month after the operation. The compar- ision of the stable rate on each
      period after the operation had no obvious difference (P=0.197>0.05), which
      indicated that the supporting effect of the titanium stick was persistent. By the
      difference of the etiology the three-year survival rate of the relevant NFH II c
      pathological changes was the lowest-70% and the survival rate of the pathological
      changes induced by other etiological factors was 90.2%. CONCLUSION: The design
      about the hollowed titanium stick supporting the collapsed femoral head is
      feasible. Using the hollowed titanium stick to support the femoral head and
      prevent it from collapsing is pragmatic in the clinical and the effect is
      positive, however, when it comes to the NFH II c pathological changes, the choice
      should be made discreetly.

PMID- 21870396
TI  - [Treatment of senile osteoporotic vertebral compression fractures with
      percutaneous kyphoplasty].
AB  - OBJECTIVE: To evaluate the clinical outcome of percutaneous kyphoplasty in
      treating vertebral compression fractures. METHODS: From October 2008 to May
      2010,41 patients with osteoporotic vertebral compression fractures were treated
      with percutaneous kyphoplasty. There were 10 males and 31 females, ranging in age
      from 61 to 83 years, with an average of 67.5 years. Fracture site was from T9 to
      L4 including 65 vertebral bodies. Clinical symptom was lumbar and back pain to
      affect orthobiosis. The pain, height of vertebral body, Cobb angle, function of
      daily activities were analyzed by VAS sore, imaging data, Oswestry score before
      and after operation. RESULTS: All operations were successful and no severe
      complications were found. Bone cement leakage occurred in 7 vertebrae, but no
      clinical sympton. All lumbago obtained obviously anesis after operation. All
      patients were followed up from 7 to 26 months with an average of 14 months.
      Preoperative, postoperative and at final follow-up, VAS score was 8.38 +/- 0.60,
      2.45 +/- 0.38, 2.53 +/- 0.36, respectively; Oswestry score was 40.00 +/- 1.16,
      17.00 +/- 2.11, 15.00 +/- 1.41, respectively; height of vertebral body was (14.64
      +/- 1.30), (25.11 +/- 1.12), (23.16 +/- 1.14) mm, respectively; Cobb angle was
      (30.17 +/- 1.45) degrees, (12.10 +/- 1.37) degrees, (14.31 +/- 0.51) degrees,
      respectively. There was significant difference between postoperative and
      preoperative, and between at final follow-up and preoperative (P<0.05). There was
      no significant difference between final follow-up and postoperative (P>0.05).
      CONCLUSION: Percutaneous kyphoplasty is effective for treatment of senile
      osteoporotic vertebral compression fractures, which can expeditiously relieve
      pain and effectively recover height of vertebral body and kyphosis Cobb angle,
      has advantages of minimal trauma and good security.

PMID- 21870397
TI  - [Malleolus tunnel syndrome caused by heterotopic ossification from postoperation
      of left talus fracture: a case report].

PMID- 21870398
TI  - [Effects of tuina on muscular tension of flexor and extensor in patients with
      knee osteoarthritis].
AB  - OBJECTIVE: To study the effects of Tuina on muscular tension of flexor and
      extensor in patients with knee osteoarthritis (KOA). METHODS: From June 2009 to
      March 2010, 20 patients with KOA were observed, including 7 males and 13 females,
      the age ranged from 42 to 72 years with an average of 61 years. Eight patients
      were ailed with single knee, 12 patients were ailed with double knee. The
      maneuver of Tuina were Gun maneuvers (120 to 140 times per minute), An maneuvers,
      Na maneuvers and Ca maneuvers. The patients were treated 3 times every week,and
      10 times were 1 course of treatment. The muscular tension of flexor and extensor
      were measured before and after treatment, and the press force of the point
      reached largest of L 500 g when the press was 500 g. The therapeutic effects were
      assessed by WOMAC (including pain, stiffness, functional activity and overall
      score) scale before and after treatment. RESULTS: There was significant increase
      in the ill knee on L 500 g (P<0.01). There was significant decrease after
      treatment in WOMAC (P<0.01). There was significant positive correlation between
      the improvement rate of extensor and the improvement rate of therapeutic effects
      (P<0.01, r=0.764). There was significant positive correlation between the
      improvement rate of flexor and the improvement rate of therapeutic effects
      (P<0.01, r2=0.533). CONCLUSION: Tuina can improve muscular tension of flexor and
      extensor in patients with knee osteoarthritis, thus can improve the therapeutic
      effects.

PMID- 21870399
TI  - [The clinical research of the relation between the pain and the disc herniation
      type].
AB  - OBJECTIVE: To evaluate the preoperative pain degree of lumbar intervertebral disc
      herniation and analyzed its reason. METHODS: From January 2002 to December
      2008,265 patients with lumbar intervertebral disc herniation were operated by
      single segment, of which site in L4,5 was 128 cases and in L5S1 was 137 cases.
      There were 162 males and 103 female, ranging in age from 21 to 78 years, with an
      average of 46.3 years. Oswestry index of all patients was observed before
      operation. The patients were divided into five groups based on Carragee system
      (according to degree of nucleus pulposus herniation and degree of fibrous ring
      cleavage to group, prolapse and liberation of nucleus pulposus with small ring
      cleavage was group I; prolapse and liberation with large ring cleavage was group
      II; contained fragment with integrated fibrous ring was group III; no contained
      fragment with integrated fibrous ring was group IV; calcified nucleus pulposus
      with degenerative fibrous ring was group V). The associativity between five types
      of lumbar intervertebral disc herniation and preoperative pain degree was
      analyzed. RESULTS: The preoperative pain in group I and group II was more severe
      than that of other groups (P<0.01). The preoperative pain in group II was more
      severe than that of group I (P<0.01). CONCLUSION: Nucleus pulposus can migrated
      into the spinal canal and will aggravate the nerve root pain if lumbar
      intervertebral disc herniation accompanies with fibrous ring cleavage; and freed
      materials can aggravate the nerve root pain by the chemical factor.

PMID- 21870400
TI  - [Design and application of inflatable pressure applicator on the treatment of
      femoral shaft fractures: case control study].
AB  - OBJECTIVE: To compare the influence on the postoperative wound healing between
      inflatable pressure applicator and traditional pressure dressing. METHODS: From
      May 2009 to February 2010, 50 patients with closed femoral shaft fractures were
      randomly divided into group A and group B, with 25 patients in each group. There
      were 13 males and 12 females in group A, ranging in age from 38 to 60 years, with
      an average of (55.1 +/- 9.5) years; of them, road accident was in 18 cases, fall
      from heigh was in 6 cases, accidental falling injury was in 1 case. There were 15
      males and 10 females in group B, ranging in age from 40 to 65 years, with an
      average of (56.5 +/- 9.2) years; of them, road accident was in 13 cases, fall
      from heigh was in 6 cases, accidental falling injury was in 6 cases. There was no
      significant difference between two groups in clinical data. The postoperative
      wounds of group A were binded with dressing of inflatable pressure applicator;
      and of group B with traditional pressure dressing. Volume of drainage at 12 h
      after operation, saturation of blood oxygen at 12, 24 h after operation,
      satisfactory rate of patients were compared between two groups. RESULTS:
      Postoperative volume of drainage in group A was lower than that of group B,
      respectively was (77.5 +/- 4.6), (94.3 +/- 3.8) ml. Saturation of blood oxygen at
      12, 24 h after operation in A group was respectively (98.3 +/- 1.1)%, (98.9 +/-
      0.8)%, and in group B was respectively (96.5 +/- 0.4)%, ( 97.0 +/- 0.3)%; there
      was significant difference between two groups at the same time. Satisfactory rate
      of patients in A group was better than that of group B. CONCLUSION: Inflatable
      pressure applicator can obviously pressurize and stop bleeding for postoperative
      wounds, but no affect on peripheral blood supply and can improve discomfort of
      patients.

PMID- 21870401
TI  - [Experimental study on the mechanism of icariin improving human osteoblasts
      proliferation and the expression of OPG protein].
AB  - OBJECTIVE: To establish the human osteoblasts culture system in vitro, observe
      the effects of icariin on human osteoblasts proliferation and expression of OPG
      protein, and to explore the mechanism of promoting bone formation about human
      osteoblast in icariin. METHODS: The femoral cancellous bone pieces were obtained
      from the operation. The enzyme digestion method was used for culturing. The third
      passage of human osteoblast was taken for experiments. The cells were divided
      into four groups, the control group was treated with 15% NCS-DMEM-F12 (1:1), the
      experimental groups were respectively treated with 10(-6), 10(-8), 10(-10) mol/L
      icariin. The MTT method was used to observe the proliferation of human osteoblast
      on 1, 3, 5, 7, 9 d; in 8, 10, 12 d, western blot was used to determine the
      expression of OPG protein on human osteoblast. RESULTS: 1) Results of MTT: the
      icariin promoted the proliferation of human osteoblast. There was a concentration
      response relation,while with the concentration of icariin increased, the ability
      was more obvious. There was statistically difference between 10(-6) mol/L icariin
      group (0.402 +/- 0.033) and the control group (0.268 +/- 0.031) (P<0.05). In the
      timely research, as the time prolong, the number of human osteoblast were more.
      At the fifth day, the human osteoblast entered rapid growth period, and access
      the growth platform stage; the icariin began to promote the proliferation of
      human osteoblast from the fifth day, which almost maintained to the 7th day and
      the 9th day, and most obvious in the 9th day. There was statistically difference
      between 10(-6) mol/L icariin group (0.402 +/- 0.033) and the control group (0.268
      +/- 0.031) at the 9th day. (The results of OPG protein expression: in the control
      group, the expression of OPG protein was detected at the 8th day (1.01 +/- 0.08),
      and reached the expression peak (1.80 +/- 0.10), there was statistically
      different (P<0.05). In the different days and different concentration icariin
      groups, the expressions of OPG protein were all inferior to the control group.
      While the concentration decreasing, the expression was less. There were
      statistically difference (P<0.05). At the day 12, there was no significant
      difference of OPG protein expression between the 10(-6) mol/L icariin group and
      the 10(-8) mol/L icariin group (P>0.05). CONCLUSION: The effect of icariin
      promoting the proliferation of human osteoblast maybe is one of the mechanisms of
      improving the bone formation on human osteoblast.

PMID- 21870402
TI  - [Experimental studies on the early treatment of soft tissue explosion injury by
      vacuum-assisted closure].
AB  - OBJECTIVE: To investigate the effect on early treatment with vacuum-assisted
      closure(VAC) to wound healing of acute explosion injury in pigs, and provide a
      new way for early treatment of battle wounds. METHODS: Eight healthy 3-month
      Landrace pigs of both sexes with the body mass of (50 +/- 5) kg were selected in
      the study. Sixteen battle wounds were made by explosion of same type detonator
      (pattern number: 660929F48840-55, included DDNP 0.3 g, RDX 0.7 g) in hibateral
      skin of buttock of 8 pigs, which were divided into experimental group and control
      group (pair wounds of left and right). The raw sufaces were thorough debrided at
      3 h after exposure, according to the characteristics of treatment on the
      battlefield, experimental group was treated with VAC under the pressure of (-50
      +/- 5) Kpa after debridement and sterilization and control group was treated with
      routine dry sterile gauze draping. Results of bacteriology (bacterial counts and
      the proportion of G+ bacteria) and pathology (HE stain and Masson stain) were
      detected at every wound before and after treatment. RESULTS: At the 3 days after
      treatment,the bacterial number in the experimental group was [(7.82 +/- 0.55) x
      10(4) ] CFU/g, in control group was [(1.07 +/- 0.14) x 10(6)] CFU/g. There was
      significant difference between two groups. The proportion of G+ bacteria in
      experimental group was significantly increased. The raw surface in experimental
      group was clean with affluent and neoformative granulation tissue, blood vessels
      and collagen, necrotic tissue decreased obviously by pathological observation.
      CONCLUSION: VAC could reduce the quantity of bacteria, improve the proportion of
      G+ bacteria, and promote the formation of granulation tissue and the healing of
      wound. The VAC for the treatment of battle wounds has a positive effect.

PMID- 21870403
TI  - [Gluteal muscle contracture release for the treatment of gluteal muscle
      contracture induced knee osteoarthritis: a report of 52 cases].
AB  - OBJECTIVE: To investigate clinical efficacy and significance of gluteal muscle
      contracture release for the treatment of gluteal muscle contracture induced knee
      osteoarthritis. METHODS: From January 2008 to June 2010,52 patients with gluteal
      muscle contracture induced knee osteoarthritis were reviewed. Among the
      patients,15 patients were male and 37 patients were female, ranging in age from
      15 to 45 years, with an average of 35 years. Eighteen patients had left knee
      osteoarthritis, 30 patients had right osteoarthritis, and 4 patients had double
      knee osteoarthritis. All the patients were treated with gluteal muscle
      contracture release. Lysholm knee score was used to evaluate therapeutic effects
      before and after operation. RESULTS: All the patients were followed up,and the
      duration ranged from 12 to 37 years,with a mean of 15 months. The Lysholm knee
      score improved from preoperative (68.12 +/- 0.78) points to postoperative (91.23
      +/- 0.47) points at the last follow-up, the difference had statistical difference
      (t=31.269, P<0.01). CONCLUSION: Gluteal muscle contracture release is effective
      to relieve symptoms of gluteal muscles contracture and knee osteoarthritis. The
      patients with gluteal muscle contracture should be treated early so as to prevent
      effects of gluteal muscle contracture on knee joint, slow down degeneration of
      knee joint at early stage, and prevent occurrence of knee osteoarthritis.

PMID- 21870404
TI  - [Surgical treatment for open dislocation of talus].
AB  - OBJECTIVE: To evaluate the clinical effects of surgical treatment for open
      dislocation of talus. METHODS: From June 2001 to July 2008,the complete data of
      11 patients with open dislocations of talus were retrospectively analyzed,
      including 8 males and 3 females with an average age of 39.5 years (ranged 19 to
      52). According to Gustilo typing, type I was in 2 cases, type II in 6 cases, type
      III A in 2 cases, type III B in 1 case. Five cases were tibial astragaloid joint
      dislocation in which 3 cases associated with subtalar joint dislocation, 4 cases
      were subtalar joint dislocation and 2 cases were total dislocation of talus.
      Among them, 8 dislocations associated with talus fractures. All patients were
      treated with debridement, open reduction, internal fixation with K-wires or
      screws and external fixation with plaster or external fixator within 8 hours
      after injury. External fixations were removed at 6 weeks after operation. Partial
      weight bearing was permitted only when X-rays indicated bony healing. Clinical
      effects were evaluated according to AOFAS system and X-ray films during follow
      up. RESULTS: The mean time of follow-up was 13.8 months(ranged 10 to 15 months).
      Eight patients with fractures obtained bone healing in 4-7 months with an average
      of 4.3 months. No infection of wound or deep tissue was found. At final follow
      up, talus necrosis was in 2 cases and traumatic arthritis was in 2 cases. The
      AOFAS score was 71.3 +/- 8.6, among the total, the pain, function, alignment was
      respectively (32.4 +/- 7.1), (31.0 +/- 15.7), (7.6 +/- 2.3) scores. CONCLUSION:
      Complete debridement may avoid infection in treating open dislocation of talus,
      early reduction and fixation is a key point during treatment.

PMID- 21870405
TI  - [Application of damage control orthopaedic for the treatment of comminuted
      fractures of superior tibia in complex injury].
AB  - OBJECTIVE: To investigate the treatment of comminuted superior tibial fracture in
      complex injury according to damage control orthopaedic. METHODS: From Jan. 2007
      to Jun. 2009,11 patients suffered from comminuted superior tibial fracture with
      complex injury, including 8 males and 3 females with an average age of 35.2
      years. The external fixator were used to fix tibial fracture in emergency
      treatment, after 6 weeks when the condition of patients were improved, fix the
      external tibia by LISS plate through litter incision, fix interior tibia by
      reconstructed plate or sustained plate. The effect evaluated by Lysholm standard,
      marking system on the basis of limp, walking stick, angina, knee unsteady, pain,
      swell, up and down floor, squat. RESULTS: All the postoperative CR showed that
      the superior tibial fractures were acquired functional reduction, the incision
      got well and no infection occurred. All 11 patients were followed-up for 12 to 18
      months with an average of 14.7 months. According to an evaluation standard of
      Lysholm, the results were excellent in 5 cases, good in 4 cases, fair in 1 case,
      poor in 1 case. CONCLUSION: According to damage control orthopaedic, the
      treatment of comminuted superior tibial fracture by external fixation and LISS
      plate is a suitable method for the patient with complex injury who undergo
      comminuted superior tibial fracture.

PMID- 21870406
TI  - [Ulnar osteotomy and internal fixation for old anterior dislocation of radial
      head in children].
AB  - OBJECTIVE: To evaluate the clinical results of ulnar osteotomy and internal
      fixation in treating old anterior dislocation of radial head in children.
      METHODS: From Jan.2004 to Jan.2010, 18 patients with old anterior dislocation of
      radial head were treated with open reduction for radial head and ulnar osteotomy
      and internal fixation, including 12 males and 6 females with an average age of
      (6.9 +/- 1.3) years (3 to 15 years). Among them, 15 cases had history of external
      injury, from injury to operation was for 5-65 months with an average of (24.0 +/-
      5.5) months. Limitation of activity occurred in all patients including flexion
      and extension of elbow joint and rotation of forearm, without radial nerve injury
      and obviously radial head deformation. RESULTS: All incisions obtained primary
      healing and no nonunion, re-dislocation of radial head and nerve injury were
      found. All patients were followed up from 9 to 38 months with an average of (17.0
      +/- 4.5) months. Union time of fracture was from 2.3 to 3.9 months with an
      average of (2.8 +/- 0.5) months. Postoperative activity in flexion and extension
      of elbow joint and rotation of forearm improved significantly compared with
      preoperative. The clinical effects were evaluated according to Zhuyukui criteria,
      14 patients got excellent results, 3 good, 1 fair. CONCLUSION: Ulnar osteotomy
      and internal fixation in treating old anterior dislocation of radial head in
      children can obtain satisfactory results and effectively improve the activities
      in flexion and extension of elbow joint and rotation of forearm and prevent re
      dislocation of radial head.

PMID- 21870407
TI  - [Treatment of odontoid process fracture with pedicle screws by location through
      inferior and inner wall of atlas and superior and inner wall of axis].
AB  - OBJECTIVE: To evaluate the therapeutic effects of atlantoaxial pedicle screw in
      treating odontoid process fracture by location through inferior and inner wall of
      atlas and superior and inner wall of axis. METHODS: From June 2006 to September
      2010, 12 patients with odontoid process fracture were treated with the
      atlantoaxial pedicle screw fixation by location through inferior and inner wall
      of atlas and superior and inner wall of axis. There were 8 males and 4 females,
      ranging in age from 18 to 62 years, with an average of 37.9 years. According to
      classification of Anderson, type II was in 10 cases and type III was in 2 cases.
      Fresh fracture was in 9 cases and old fracture was in 3 cases. All patients had
      symptoms such as cervical pain, stiffness and limitation of activity and 9 cases
      with symptoms were found physical signs of cervical spinal injury. According to
      grade of ASIA, grade C was in 4 cases and grade D was in 5 cases. RESULTS: There
      were no severe complications such as injuries of vertebral artery, nerve root and
      spinal cord during operation. The mean time of follow-up was 14 months (6 to 24
      months). The X-ray film and CT scanning showed that all patients had steady bony
      union and all screws were in the proper position, no screws loosening or breaking
      were found. Clinical symptoms of all patients improved significantly. Nine
      patients with spinal injury before operation, of which nerve function obtained
      improvement, grade C was in 1 case, grade D was in 2 cases and grade E was in 6
      cases according to grade of ASIA. CONCLUSION: Location through inferior and inner
      wall of atlas and superior and inner wall of axis is an effective method for the
      atlantoaxial pedicle screw implantation; atlantoaxial pedicle screw could be
      accurately and safely implanted thought this way.

PMID- 21870408
TI  - [Surgical treatment for spinal stenosis caused by cervicothoracic ossification of
      the posterior longitudinal ligament].

PMID- 21870409
TI  - [Treatment of fracture of surgical neck of humerus with manipulative reduction
      and external fixation].

PMID- 21870410
TI  - [Traumatic asymmetrical bilateral hip dislocation: a case report].

PMID- 21870411
TI  - [Current study and research progress of whiplash injury of cervical vertebrae].
AB  - Whiplash injury is a common injures in our daily lives, but the mechanism of it
      and the best treatment is largely unknown. The development of chronic pain and
      disability following whiplash injury is not uncommon and results in substantial
      social and economic costs. Clinical manifestation and recovery time are
      difference, which make it difficult for doctor diagnosis and treatment. The
      current study have shown that the social class, severity of collision,
      compensation and lawsuit, physical and psychological factors were relevant
      predictors for the outcome of whiplash. This article is try to overview the
      status quo of the whiplash injury.

PMID- 21870412
TI  - [Current situation and progression of induced pluripotent stem cells in treating
      spinal cord injury].
AB  - Spinal cord injury is a difficult medical problem and current therapeutic methods
      could not obtain satisfactory results. Recent 20 years, stem cell technology
      developed rapidly, embryonic stem cells and adult stem cells were used for
      treating neurological disease and nerve injury of animal models and the clinical
      results were confirmed. It provided a new prospect for the treatment of nerve
      injury at the cellular level. However,due to technical and ethical problems, it
      is difficult to obtain the appropriate cells that can be applied to the human
      being. Recently, induced pluripotent stem cells were developed as a new method
      for the treatment of spinal cord injuries by the autologous transplantation.
      Starting from this work, the purpose of this review is to assess the
      differentiate ability of induced pluripotent stem cells into neurocyte and review
      the latest developments in this area.

PMID- 21870414
TI  - [Normative values of kinetic tests in VNG assessment].
AB  - BACKGROUND: Balance assessment plays an important role in occupational medicine.
      The diagnosis of patients with balance disturbances is based on a number of
      laboratory tests, including rotational chair tests, one of the most important.
      The normative value of kinetic tests greatly depends on movement parameters and
      laboratory equipment, which vary between diagnostic centers. The aim of the
      presented paper was to establish normatives for our laboratory and testing
      methodology in a group of healthy persons. MATERIALS AND METHODS: The balance
      examination included 45 healthy persons (21 women and 24 men) aged 20-63 years
      (mean 38.5 +/- 14.9). The study population underwent very thorough neuro
      otological examination, static posturography and VNG tests. The caloric test
      result was a crucial criterion for inclusion to the group of healthy persons.
      Rotational tests included: one "burst" test analyzing vestibulo-ocular reflex
      (VOR) with and without optokinetic stimulation visual vestibular optokinetic
      reflex (VVOR) and cervico-ocular reflex (COR); three impulse tests and sinusoidal
      harmonic rotation tests of 0.04, 0.08, 0.1, 0.16, 0.32, and 0.64 Hz. RESULTS: The
      mean values were: VVOR, 0.9 +/- 0.1; VOR, 0.5 +/- 0.1; and COR, 0.2 +/- 0.1. The
      mean value of rotational and post-rotational nystagmus induced by sudden chair
      stop (impulse stimulus) was 9 +/- 7 s, the gain values were 0.4 for sinusoidal
      tests, in the stimulation range of 0.1-0.32 and 0.5 for 0.64 Hz stimulation.
      There was no significant linear relationship between age and test parameters
      except for the test using sinusoidal-decreasing stimulation. CONCLUSIONS: These
      normative values form the base for a closer incorporation of rotational tests in
      occupational medicine procedures.

PMID- 21870413
TI  - [Color vision impairment in workers exposed to mercury vapor].
AB  - INTRODUCTION: Acquired reversible dyschromatopsia has been associated with
      occupational exposure to mercury vapor. Early-detected impairments in color
      discrimination precede adverse permanent effects of mercury, so they may help to
      monitor the health of the exposed workers. The aim of this study was to evaluate
      the color discrimination ability in this group of workers, using Lanthony D-15d
      test. MATERIAL AND METHODS: Employed in a chloralkali plant, 27 male workers
      exposed to mercury vapor and 27 healthy white-collar workers (control group) were
      qualified for the study. To assess color discrimination, the Lanthony 15-Hue
      desaturated test (Lanthony D-15) was used. In order to investigate quantitative
      and qualitative results, the Lanthony D-15d scoring software was performed.
      Urinary mercury was determined using flameless atomic absorption spectrometry.
      RESULTS: In the workers exposed to mercury vapor, urine mercury concentration was
      117.4 +/- 62.6 microg/g creatinine on average compared with 0.279 +/- 0.224 mg/g
      creatinine in the control group (p < 0.0001). In 18 exposed persons (66.7%), the
      results of the Lanthony D-15d test showed qualitative changes, which are
      borderline corresponding to the early stage of developing dyschromatopsia type
      III. The quantitative analysis of the test findings indicated a significantly
      higher value of the Color Confusion Index (CCI) in the right eye in the exposed
      group compared to the control group (p = 0.01), with no significant difference in
      the CCI in the left eye. In the exposed group, the CCI in the right eye was
      significantly higher than the CCI in the left eye (p = 0.0005). There was neither
      correlation between CCI and the level of urinary mercury, nor between CCI and
      duration of exposure. CONCLUSIONS: The results showed that the Lanthony D-15d
      test is useful in the detection of early toxic effects in the eyesight of the
      workers exposed to mercury vapor. The observed color vision impairments are
      borderline corresponding to the early stage of developing dyschromatopsia type
      III.

PMID- 21870415
TI  - [Person-organization fit and work ability].
AB  - BACKGROUND: Person-environment issue has long been in focus of researchers who
      explore the area of human labor. It is known that the level of fit is a predictor
      of many phenomena related to health and attitude to work. The aim of this study
      was to explore the association between the level of person- organization fit (P-O
      fit) and work ability, including indicators of somatic and mental health.
      MATERIALS AND METHODS: Research was conducted on a representative sample of 600
      Polish men and women at working age. The Person-Organization Fit Questionnaire
      was used to assess three dimensions of P-O fit (supplementary fit, complementary
      fit and identification with organization); mental health status was measured by
      GHQ-28; the number of diagnosed diseases was taken as an index of somatic health;
      work ability, ability to physical and mental efforts were measured by three items
      from the Work Ability Index. RESULTS: A significant relationship between P-O fit
      level and work ability was found. In men, work ability predictors were: age,
      supplementary fit and mental health status, which explained 25% of the variance
      in work ability. In women, work ability predictors were: the number of diagnosed
      somatic diseases, supplementary fit, age and complementary fit, which explained
      27% of the variance in work ability. Some gender-related differences in the
      predictive value of variables under the study were also found. CONCLUSIONS: The
      results of this study indicate the importance of P-O fit in shaping the sense of
      work ability, a recognized predictor of workers' occupational activity and the
      frequency of taking sick leave in subsequent years. Therefore, this result may be
      a useful argument to motivate employers to employ workers adequately to their
      abilities and preferences.

PMID- 21870416
TI  - [Moulds isolated from the upper sections of the respiratory and alimentary tracts
      of healthy veterinary medicine students].
AB  - BACKGROUND: The mycological studies in healthy veterinary medicine students have
      been prompted by the fact that only a few publications are available to date on
      the occurrence of moulds in people identifying themselves as generally healthy
      and having direct contact with ill or dead animals. MATERIAL AND METHODS: The
      research material comprised swabs from the oral cavity, nasal cavity and throat
      of one hundred students (Faculty of Veterinary Medicine, University of Warmia and
      Mazury in Olsztyn) who declared good health. Initial cultures on the Sabouraud
      medium were incubated for 72 h at 37 degrees C, then sieved in the Czapek-Dox
      medium, where they were macroscopically assessed after two weeks. Forcing
      preparations produced with use of adhesive tape, were stained methylene blue with
      lactofenol. RESULTS: The studies identified 9 species of fungi from four genera:
      Aspergillus and Penicillium (mould), Scopulariopsis and Trichophyton
      (dermatophytes). Penicillium chrysogenum was a dominant feature. Aspergillus
      fumigatus, Aspergillus niger, A. versicolor and Scopulariopsis brevicaulis were
      often isolated. Moulds were also accompanied by yeast-like fungi (Candida
      albicans, Candida tropicalis). Most of the fungi were isolated from the nasal
      cavity of nicotine abusers and those taking oral hormones. CONCLUSIONS: Isolation
      of potentially pathogenic fungi from people declaring good health may indicate
      the carrier state or a lowered resistance at the time of material collection.
      This indicates the need to put a greater emphasis on prevention in subsequent
      mycological examinations of environmental risk groups.

PMID- 21870417
TI  - [Professional image of nurses as perceived by doctors, patients and nurses
      themselves].
AB  - BACKGROUND: The study was aimed at comparing the perception of the nurses'
      professional image by three groups: doctors, patients and nurses. The following
      elements of the image were taken into account: professional, personal and
      interpersonal characteristics as well as general beliefs on the nursing
      profession. MATERIAL AND METHODS: The examined group consisted of 160
      participants: 50 doctors, 50 patients and 60 nurses employed or currently treated
      in provincial and district hospitals. To test the professional image of nurses a
      new measurement tool has been developed. It permits to assess professional,
      personal and interpersonal characteristics attributed to nurses and selected
      beliefs on the nursing profession. The study took into consideration the
      following socio-demographic factors: gender, age, marital status, place of
      residence, education and setting, and also profession-related factors (job
      seniority; additional courses and specializations) as regards doctors and nurses
      and occupational activity and relations with nurses as regards patients. RESULTS:
      The surveyed groups differed in their assessment of a majority of characteristics
      attributed to nurses. The characteristics were appraised lower by doctors than by
      nurses, which indicates a more negative attitude of the former. The patients'
      appraisal was also lower than that of nurses, except for mental strength and
      tidiness. However, nurses perceived their professional position in the society
      and medical profession as the lowest. The characteristics, which did not differ
      in their assessment between groups were analyzed as well. CONCLUSIONS: The study
      allowed determining those elements of the nurses' professional image, whose
      appraisal differed between the surveyed groups. In spite of the existing common
      elements, the differences dominated. In the majority of the analyzed elements the
      nurses' evaluation was higher than that of doctors and patients, which indicates
      that they demonstrate more positive image of the profession than the other
      groups.

PMID- 21870418
TI  - [Effect of fatigue on the fitness to drive].
AB  - The 1995 U.S. Department of Transportation files contain a statement that driver
      fatigue has been a major problem among road vehicle professional drivers, while
      the consequences of participation in public road traffic of drivers affected by
      fatigue represent a serious threat to the public safety. Therefore, studies on
      the causes and consequences of fatigue in drivers are of significant practical
      value. The authors of this work discuss definitions of fatigue and fatigue
      classifications relative to the location of the functional changes (physical and
      mental fatigue, general and local - muscular, ocular, auditory) and relative to
      intensity (acute, sub-acute, chronic fatigue and weariness), and duration
      Particular attention has been paid to the factors contributing to fatigue in
      drivers. These may be classified into two groups: 1. sleep-related (SR), i.e.
      cumulative sleep deficit, long wake time, and time of the day; 2. task-related
      (TR), i.e. factors related with vehicle driving and working (driving) time.
      Studies on the effect of fatigue on driving performance (longer reaction time,
      poorer vigilance, slower information processing, impaired recent memory) have
      been analyzed. The major effect of driver fatigue is that he/she becomes
      gradually diverted from the road and road traffic, with the resultant poorer
      driving performance. Thus, the effects of fatigue in a driver are comparable to
      those after alcohol intake. This paper also discusses the methods used to
      counteract and prevent fatigue.

PMID- 21870419
TI  - [Protection of medical diagnostic laboratory workers against biohazards].
AB  - Medical diagnostic laboratories form a particular occupational environment, in
      which workers have contact with patients and potentially infectious biological
      materials thus it should be acknowledged that it poses a significantly increased
      risk to health of laboratory workers. The risk directly depends on the kind of
      microbes present in a biological material and natural resistance to infections of
      individual workers. Therefore, the adopted technical and organizational
      solutions, properly worked out and obeyed procedures assuring safety work with
      biological material and microbes and properly trained laboratory staff play an
      essential role in reducing the risk. The risk of contact with microbes among
      laboratory workers is higher in Poland than in a number of other countries
      because hermetic devices for diagnostic analyzes and safety blood sampling
      systems are not always in use. The most important methods of infectious diseases
      prevention among laboratory workers are to protect them against direct contact
      with biological material, to apply vaccinations and to implement proper post
      exposure procedures. Appropriate qualifications and habits of workers are of
      relevance to prevent infections in laboratories. A difficult financial situation
      of health care in Poland and other economic reasons can significantly increase
      the risk of infections and endanger health and safety of laboratory workers. It
      is necessary to develop practical instructions aimed at improving occupational
      safety to protect this occupational group against harmful effects of biological
      agents.

PMID- 21870420
TI  - [Impact of the legislation for smoke-free workplaces on respiratory health in
      hospitality workers--review of epidemiological studies].
AB  - Environmental tobacco smoke exposure (ETS) is a significant risk factor for the
      development of many diseases, including lung cancer, lower respiratory tract
      infections, asthma and eye, throat and nasal irritations. Hospitality workers
      form an occupational group with high exposure to ETS in their workplace. Taking
      into account the health consequences of ETS exposure and high prevalence of
      exposure in public places, including workplaces, many countries have implemented
      the smoking ban that prohibits or restricts smoking in workplaces, including
      restaurants and bars. The epidemiological studies have indicated a significant
      reduction in the exposure level after implementation of the smoking ban. Most
      studies have also indicated a significant reduction in respiratory and sensory
      symptoms. The impact of the smoking ban on the lung function measurements is
      still not clear.

PMID- 21870421
TI  - [Exposure to static magnetic field and health hazards during the operation of
      magnetic resonance scanners].
AB  - Magnetic resonance imaging (MRI) scanners belong to the most modern imaging
      diagnostic devices, which involve workers' exposure to static magnetic fields
      (SMF) during the preparation and performance of MRI examinations. This paper
      presents the data on workers' exposure to SMF in the vicinity of MRI scanners and
      the analysis of SMF-related biological effects and health hazards to find out
      whether softening the legislative requirements concerning protection against SMF
      exposure of workers involved in MRI diagnostics is justified. Measurements in the
      vicinity of 1.5 T MRI magnets showed that exposure to SMF by various scanners
      depends on both SMF of magnets and scanners design, as well as on work
      organization. In a routine examination of one patient the radiographer is exposed
      to SMF exceeding 0.5 mT for app. 1.5-7 min, and up to 1.3 min to SMF exceeding 70
      mT. In examinations of patients who need more attention, the duration of exposure
      may be significantly longer. The mean values (B mean) of exposure to SMF are 5.6
      85 mT (mean 30 +/- 19 mT, N = 16). These data demonstrate that only well designed
      procedures, proper organization of workplace and awareness of workers how to
      attend the patients without being exposed to strong SMF allow for meeting the
      requirements of labor law concerning workers' exposure to SMF. The analysis of
      the available literature on biological effects of SMF has disclosed the lack of
      data on health effects of many years exposure of workers and the abundance of
      data demonstrating the biological activity of SMF. Therefore, a radical softening
      of legislative requirements concerning the exposure of workers' head or trunk is
      premature, and what is more, it is not indispensable for the development of MRI
      diagnostic. Such an action should be preceded by extensive international
      investigations on the health status of workers exposed to electromagnetic fields
      by MRI scanners.

PMID- 21870422
TI  - [Night shift work and cancer risk: a literature review].
AB  - About 15-20% of the employees in Europe and in the USA are engaged in shift work
      that involves night work. Some experimental and observational data indicate that
      this type of work might lead to circadian disruption, including disruption in the
      melatonin synthesis - a hormone of anticarcinogenic and antioxidative properties.
      A hypothesis that there is a potential link between exposure to light at night
      and the risk of breast cancer was formulated for the first time by Stevens in
      1987. Since then, relatively few epidemiological studies have been carried out in
      this area (15 studies including 8 cohort and 7 case-control studies). All of them
      are reviewed in this article. The majority of the epidemiological studies
      performed to date have focused on the association between shift work and breast
      cancer risk, few studies have reported an increased risk of other cancers,
      including colorectal cancer, endometrial cancer, prostate cancer and non
      Hodgkin's lymphoma. In six out of ten studies, a statistically significant
      association between night shift work and risk of breast cancer has been shown (OR
      = 2.2; 95% CI: 1.1-4.5 in nurses in Norway with > 30 years of night shift work).
      The increased cancer risk has been reported in nurses, radio-telephone operators,
      flight attendants, and women employed in the enterprises, in which 60% of
      employees work at night. Most of the analyses have been based on the data from
      the registries, with limited potential for the exposure assessment and
      confounders adjustment. Although some epidemiological studies suggest an
      increased risk of breast cancer among nurses, we are still far from drawing final
      conclusions. Therefore, further epidemiological studies are warranted.

PMID- 21870423
TI  - [Coexistence of two occupational infectious diseases in one patient--borreliosis
      and tick-borne encephalitis--a case report].
AB  - Recently, infectious diseases have been found to be the most frequent among
      occupational diseases. Borreliosis, the most common among them, as well as tick
      borne encephalitis is transmitted by ticks. Recognition of occupational etiology
      of such diseases is possible only when the relationship between the infection,
      occupational exposure and performed work is proved. A case report of a forest
      worker with borreliosis coexisting with tick-borne encephalitis is presented.
      Despite nonconcurrent recognition of both diseases it was highly possible that
      contagion took place at the same time or at a very short time interval. Despite
      high prevalence of tick-borne diseases, occupational etiology of these two
      infectious diseases in one patient is very rarely recognized.

PMID- 21870424
TI  - Ethno biological usage of zoo products in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is one of the most common autoimmune disorder which
      causes swelling, redness, pain, stiffness, restriction of limb movements,
      decreases life expectancy and early death of the patients. Available drugs
      include non steroidal anti-inflammatory and analgesics, disease modifying anti
      rheumatic drugs and steroids (glucocorticoids etc). All these drugs have their
      own limitations such as gastrointestinal irritations, cardiovascular problems,
      and drug dependency. Search for alternative therapy from natural products are
      being ventured throughout the world. Zoo therapy in arthritis, a common practice
      of the ancient times that have been mentioned in traditional and folk medicine.
      The scientific basis of some of the zoo products are being explored and have been
      showing promising results in experimental rheumatoid arthritis. These therapies
      have minimum side effects and many of them have potential to give rise to drug
      development clues against rheumatoid arthritis. The present review is an effort
      to establish the folk and traditional treatment of rheumatoid arthritis using zoo
      products.

PMID- 21870425
TI  - Inhibition of subcutaneous growth of Ehrlich ascites carcinoma (EAC) tumor by
      post-immunization with EAC-cell gangliosides and its anti-idiotype antibody in
      relation to tumor angiogenesis, apoptosis, cell cycle and infiltration of CD4+,
      CD8+ lymphocytes, NK cells, suppressor cells and APC-cells in tumor.
AB  - Both EAC-tumor associated gangliosides and its anti-idiotype antibody inhibited
      growth of this tumor significantly. Immuno-histological studies with von
      Willebrand Factor (vWF) antibody indicated that tumor angiogenesis as determined
      by expression of vWF decreased in tumors of mice, post-immunized with EAC-cell
      gangliosides as well as its anti-idiotype antibody. Infiltration of various
      immune cells of the host in the tumor correlated to some extent with tumor-growth
      inhibition. Apoptosis study using AnnexinV-FITC and propidium iodide indicated
      that tumor growth inhibition in mice post-immunized with EAC-gangliosides and its
      anti-idiotype antibody were due to enhanced apoptosis and cell death. Cell cycle
      analysis by FACS indicated that EAC-cell associated gangliosides and its anti
      idiotype antibody were acting both at the M2 i.e. S and M3 i.e. G2/M phases of
      the cell cycle to arrest tumor growth.

PMID- 21870427
TI  - Expression of rabies virus glycoprotein gene into eukaryotic system and
      determination of potential T-cell epitopes.
AB  - The present study was undertaken to clone, express rabies virus glycoprotein
      (RVG) and to identify potential T-cell epitopes on it. RVG gene (1590 bp) was
      amplified using gene specific primers. The amplified product was cloned into
      pTZ57R/T cloning vector by TA cloning. RVG gene was subcloned into pcDNA3.1 (+)
      expression vector. In this study, cloning and expression of rabies virus
      glycoprotein gene was done under CMV promoter and an expression construct
      (pcDNA.RVG) was prepared and clones were confirmed by restriction digestion,
      colony PCR and nucleotide sequencing. The expression construct was further
      characterized by western blotting and indirect fluorescent antibody test (IFAT).
      In silico analysis of this protein was done to find out potential antigenic sites
      so that it can be further evaluated for its potential as candidate for epitope
      vaccine against rabies.

PMID- 21870426
TI  - Effects of beta-arrestin 2 on cytokine production of CD4+ T lymphocytes of mice
      with allergic asthma.
AB  - Beta-arrestin 2 has been shown to participate in the pathogenesis of asthma by
      inducing Th2 cell migration to the lungs. Whether beta-arrestin 2 regulates
      cytokine production of CD4+ T cells is still unknown. The aim of the present
      study was to investigate the effect of beta-arrestin 2 on the cytokine production
      of CD4+ T lymphocytes and the mechanism involved in a mouse model for asthma.
      After silencing beta-arrestin 2 expression in CD4+ T lymphocytes from asthmatic
      mice by RNA interference (RNAi), the interleukin-4 (IL-4) and interferon-gamma
      (IFN-gamma) levels in CD4+ T lymphocyte culture supernatants with or without
      terbutaline stimulation were determined. Cell-surface beta2 adrenergic receptor
      (beta2AR) as well as GATA3 expression of CD4+ T lymphocytes were also measured.
      CD4+ T lymphocytes of mice with allergic asthma expressed higher levels of beta
      arrestin 2 on both mRNA and protein levels. beta-arrestin 2 RNAi decreased IL-4
      (43.16%) and GATA3 (protein 77.21%, mRNA 62.98%) expression after terbutaline
      stimulation. Cell-surface beta2AR of CD4+ T lymphocytes decreased (15.27%) after
      terbutaline treatment, but recovered after beta-arrestin 2 RNAi down-modulation.
      These findings demonstrate that beta-arrestin 2 regulates IL-4 production and
      GATA3 expression of CD4+ T lymphocytes partly through the beta2AR signaling
      pathway in an allergic asthma model.

PMID- 21870428
TI  - Sensitivity of last larval stadium of Chrysomya megacephala (Fabricius) to anti
      allatin ageratochromene Precocene II.
AB  - Treatment of early and late third instar larvae of economically important insect
      C. megacephala with the ageratochromene precocene II resulted into precocious
      metamorphosis. The other effects included mortality, production of pupal-adult
      mosaics, reduction in percentage of adult emergence and formation of non-viable
      deformed adults that died after a few hours of emergence. The application of
      precocene II adversely hampered the normal growth, development and metamorphosis
      of the insect and the results show that precocene II has vast potential for
      excellent control of this insect of medico-veterinary importance and can be used
      in insect pest management programs.

PMID- 21870429
TI  - Possible nitric oxide mechanism in the protective effect of hesperidin against
      ischemic reperfusion cerebral injury in rats.
AB  - Stroke is the third leading cause of death and disability around the globe. The
      aim of the present investigation was to evaluate the protective effect of
      hesperidin and its nitric oxide mechanism against cerebral ischemia reperfusion
      injury. Bilateral common carotid artery occlusion for 30 min followed by 24 h
      reperfusion was given to induce ischemia in rats. Animals were pretreated with
      hesperidin (50 and 100 mg/kg, po) for 7 days. Various behavioural tests,
      oxidative stress parameters, endogenous antioxidant system, antioxidant enzyme
      activity and mitochondrial enzyme complex (I, II, III and IV) dysfunctions in
      cortex and striatum were assessed subsequently. Hesperidin (50 and 100 mg/kg)
      significantly improved neurobehavioral alterations (neurological score, locomotor
      activity, resistance to lateral push and hanging wire latency), attenuated
      oxidative damage, restored antioxidant and mitochondrial complex enzyme
      activities in cortex and in striatum regions of the brain as compared to their
      respective controls. L-arginine (100 mg/kg) or L-NAME (10 mg/kg) pretreatment
      with lower dose of hesperidin (50 mg/kg) significantly reversed or potentiated
      its protective effect, respectively which was significant as compared to
      hesperidin (50 mg/kg). The results highlight the involvement of nitric oxide
      mechanism in the protective effect of hesperidin against ischemia reperfusion
      injury induced alterations.

PMID- 21870430
TI  - Anti-depressant-like activity of a novel serotonin type-3 (5-HT3) receptor
      antagonist in rodent models of depression.
AB  - N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3 antagonist
      identified from a series of compounds with higher pA2 (7.6) and good log P (2.91)
      value was screened in rodent models of depression such as forced swim test (FST),
      tail suspension test (TST), interaction studies with standard anti-depressants
      and confirmatory studies such as reversal of parthenolide induced depression and
      reserpine induced hypothermia. In FST (2 and 4 mg/kg) and TST (2 and 4 mg/kg),
      QCM-13 significantly reduced the duration of immobility in mice without affecting
      the base line locomotion. QCM-13 (2 and 4 mg/kg) was also found to have
      significant interaction with standard anti-depressants (fluoxetine and bupropion
      in FST and TST respectively). Further, reversal of parthenolide induced
      depression in mice and reserpine induced hypothermia in rat models indicate the
      serotonergic influence of QCM-13 for anti-depressant potential.

PMID- 21870431
TI  - Evaluation of antioxidant and neuroprotective effect of date palm (Phoenix
      dactylifera L.) against bilateral common carotid artery occlusion in rats.
AB  - The cerebral ischemia in rats was induced by occluding bilateral common carotid
      arteries (BCCAO) for 30 min., followed by 45 min reperfusion. BCCAO caused
      significant depletion in superoxide dismutase, catalase, glutathione, glutathione
      peroxidase, glutathione-S-transferase, glutathione reductase and significant
      increase in lipid peroxidation along with severe neuronal damage in the brain.
      All the alterations except depletion in glutathione peroxidase and glutathione-S
      transferase levels induced by cerebral ischemia were significantly attenuated by
      15 days pretreatment with methanolic extract of P. dactylifera fruits (100, 300
      mg/kg), whereas 30 mg/kg dose was insignificant in this regard. These results
      suggest the possible use P. dactylifera against bilateral common carotid artery
      occlusion induced oxidative stress and neuronal damage.

PMID- 21870432
TI  - Effect of exposure to extremely low electro-magnetic field during prenatal period
      on mice spleen.
AB  - Total body weight of newborns, the volume of spleen, and the number of
      megakaryocytes decreased following the exposure to ELF-MF (6 x 10(-3) T and 50
      Hz) at 1-5, 6-10, 11-15, and 16-20 days of pregnancy of mice. The complete period
      of gestation was sensitive to ELF-MF exposure; the initial days were more prone
      to exposure. The results suggest that the use of ELF-MF producing instruments
      should be limited during gestation.

PMID- 21870433
TI  - In fairness to cities.

PMID- 21870434
TI  - The best and the brightest.

PMID- 21870435
TI  - The stress of crowds.

PMID- 21870436
TI  - New help for smokers.

PMID- 21870437
TI  - Her summer pastime? Cancer research. Interview by John Matson.

PMID- 21870438
TI  - Straight talk about vaccination.

PMID- 21870439
TI  - Password prevented.

PMID- 21870440
TI  - Street-savvy.

PMID- 21870441
TI  - The social nexus.

PMID- 21870442
TI  - Engines of innovation.

PMID- 21870443
TI  - Bigger cities do more with less.

PMID- 21870444
TI  - Global bazaar.

PMID- 21870445
TI  - Brains over buildings.

PMID- 21870446
TI  - How green is my city.

PMID- 21870447
TI  - All climate is local.

PMID- 21870448
TI  - The efficient city.

PMID- 21870449
TI  - Castles in the air.

PMID- 21870451
TI  - Life in the meta city.

PMID- 21870450
TI  - Street talk.

PMID- 21870452
TI  - What is pseudoscience?

PMID- 21870453
TI  - The human cost of energy.

PMID- 21870454
TI  - Medical applications of nanoparticles in biological imaging, cell labeling,
      antimicrobial agents, and anticancer nanodrugs.
AB  - This article reviews the applications of nanotechnology in the fields of medical
      and life sciences. Nanoparticles have shown promising applications from diagnosis
      to treatment of various types of diseases including cancer. In this review, we
      discuss the applications of nanostructured materials such as nanoparticles,
      quantum dots, nanorods, nanowires, and carbon nanotubes in diagnostics,
      biomarkers, cell labeling, contrast agents for biological imaging, antimicrobial
      agents, drug delivery systems, and anticancer nanodrugs for treatment of cancer
      and other infectious diseases. The adverse affects of nanoparticles on human skin
      from daily use in cosmetics and general toxicology of nanoscale materials are
      also reviewed.

PMID- 21870455
TI  - Cationic polymer based nanocarriers for delivery of therapeutic nucleic acids.
AB  - The design and development of nucleic acids based therapeutics for the treatment
      of diseases arising from genetic abnormalities has made significant progress over
      the past few years. Advances in synthetic oligonucleotide chemistry resulted in
      synthesis of nucleic acids that are relatively stable in in vivo environments.
      However, cellular targeting and intracellular delivery of nucleic acids still
      remains a challenge. Further, development of nucleic acids based therapeutics
      depends on the progress of safe and effective carriers for systemic
      administration. Cationic vectors with diminished cytotoxicity and enhanced
      efficacy are rapidly emerging as systems of choice. These vectors protect nucleic
      acids from enzymatic degradation by forming condensed complexes along with
      targeted tissue and cellular delivery. During the past few years, myriad of
      reports have appeared reporting delivery of nucleic acids mediated by
      nanocarriers. This review provides an overview of various nanocarriers employed
      for in vitro and in vivo delivery of therapeutically relevant nucleic acids e.g.,
      DNA, siRNA, LNA, PNA etc.

PMID- 21870456
TI  - Curcumin loaded fibrinogen nanoparticles for cancer drug delivery.
AB  - In this work we prepared and evaluated the curcumin loaded fibrinogen
      nanoparticles (CRC-FNPs) as a novel drug delivery system for cancer therapy.
      These novel CRC-FNPs were prepared by a two-step co-acervation method using
      calcium chloride as the cross-linker. The prepared nanoparticles were
      characterized using dynamic light scattering (DLS), atomic force microscopy
      (AFM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TG),
      differential thermal analysis (DTA) and X-ray diffraction (XRD) studies. DLS
      studies showed that the particle size of CRC-FNPs was in the range of 150-200 nm.
      The loading efficiency (LE) and in vitro drug release were studied using UV
      spectrophotometer. The LE was found to be 90%. The cytotoxicity was studied using
      L929 (mouse fibroblast), PC3 (prostate) and MCF7 (breast) cancer cell lines by
      MTT assay, which confirmed that CRC-FNPs were comparatively non toxic to L929
      cell line while toxic to PC3 and MCF7 cancer cells. Cellular uptake of CRC-FNPs
      studied using L929, MCF-7 and PC3 cells monitored by fluorescent microscopy,
      demonstrated significant internalization and retention of nanoparticles inside
      the cells. The preferential accumulation of curcumin within the cancer cells were
      also confirmed by flowcytometry based uptake studies. The apoptosis assay showed
      increased apoptosis on MCF-7 compared to L929 cells. The blood compatibility of
      CRC-FNPs throws light on the fact that it is possible to administer the prepared
      nanoformulation intravenously. The results indicated that CRC-FNPs could be a
      promising therapeutic agent for cancer treatment.

PMID- 21870457
TI  - Exploration of the relationship between the tumor burden and the concentration of
      vascular endothelial growth factor in liver-cancer-bearing animals using
      immunomagnetic reduction assay.
AB  - To achieve early-stage diagnosis, a high-sensitivity assay method is needed. As a
      biomarker, vascular endothelial growth factor (VEGF) has played a growing role in
      diagnosing and treating hepatocellular carcinoma (HCC). In this work, an
      immunomagnetic reduction (IMR) through bio-functionalized magnetic nanoparticles
      and a high-temperature superconducting-quantum-interference-device magnetometer
      were utilized for quantitative detection of low-concentration VEGF in serum from
      rats with HCC. The precision and accuracy of IMR on VEGF were characterized.
      Further, the results of assaying VEGF in the serum of rats were compared with
      those of using enzyme-linked immunosorbant assay (ELISA). It was found the
      correlations between the detected VEGF concentration in the rat serum and tumor
      burdens were 0.99 and 0.90 for IMR and ELISA, respectively, within the range from
      2 pg/ml to 8000 pg/ml of VEGF concentration.

PMID- 21870458
TI  - The effects of replacing collagen fibers with carbon nanotubes on the rate of
      bone remodeling process.
AB  - Application of carbon nanotubes (CNTs) instead of collagen fibers (CFs) in bone
      tissue is one of the proposed avenues for the enhancement of bone's mechanical
      properties. The mechanical behavior improvement caused by such a replacement is
      somehow guaranteed because of the superior mechanical properties of CNTs compared
      to those of CFs. But on the other side, bone is a very active and dynamic tissue,
      which is maintained through a lifelong coupled process of resorption and
      formation in order to reach an optimal configuration. Hence, the well accepted
      fact of the bone remodeling dependency on mechanical stimuli besides the
      differences in mechanical behavior of CNTs and CFs under loading can encourage
      one to hypothesize that such a replacement would cause an imbalance in the normal
      rate of bone remodeling process. Results of our finite element analysis indicate
      that the application of CNTs instead of CFs can cause a significant reduction in
      strain energy density, assumed here as the mechanical stimulus to initiate the
      bone remodeling process. Our results also show that this replacement may change
      the strain energy distribution within the bone. Based on a semi-mechanistic bone
      remodeling theory, it is speculated that this alteration in strain energy
      distribution in artificial bone can destabilize normal bone remodeling process,
      and therefore it is likely to cause some abnormalities in bone's mechanical and
      biological functions.

PMID- 21870459
TI  - Preparation and characterization of nano-hydroxyapatite/poly(vinyl alcohol)
      composite membranes for guided bone regeneration.
AB  - In this study, nano-hydroxyapatite/poly(vinyl alcohol) (n-HA/PVA) composite
      membranes were prepared by solvent casting and evaporation method. The
      morphology, mechanical properties, water absorption behavior, contact angle
      measurement and biocompatibility of these membranes were examined by SEM, FTIR,
      XRD, MTT assay and etc. The results demonstrate that the surface of composite
      membranes is suitable for the adhesion and proliferation of osteogenic cells, and
      that n-HA and PVA are in uniform distribution when the content of n-HA is less
      than 20 wt%. Tests of swelling behavior and water contact angle show that the
      incorporation of n-HA into PVA matrix significantly reduces its hydrophilicity.
      Mechanical tests reveal that the addition of n-HA nanoparticles reduces tensile
      strength and elongation rate but increases Young's modulus of composite
      membranes. Cell attachment test and MTT assay prove that n-HA/PVA composite
      membranes have good biocompatibility. Therefore, the n-HA/PVA composite membranes
      possess potential application for guided bone regeneration (GBR).

PMID- 21870460
TI  - Preparation, characterization and cytotoxicity evaluation of tanshinone IIA
      nanoemulsions.
AB  - Tanshinone IIA (TA) is a major active component of Danshen (Salvia miltiorrhiza
      bunge), a well-known traditional Chinese medicine. In this paper, we describe an
      optimal method for preparing TA nanoemulsions (TA-NEs) to solve the problems of
      TA's poor solubility in water and insufficient dissolution rate. Optimization of
      the method for preparing nanoemulsions of lipid soluble TA by emulsification/high
      pressure homogenization was carried out with a 2(3) factorial design, using Tween
      80, lecithin and water content as independent variables. The particle size,
      entrapment efficiency and polydispersity index of eight formulations were then
      evaluated. Two optimal formulations, TA-NE-F2 and TA-NE-F4, were developed and
      both exhibited markedly enhanced in vitro release ability, as compared to TA.
      However, only TA-NE-F4 remained stable for over 3 months. TA-NE-F4 particles were
      spherical and intact, with a mean particle size of 95.6 nm and a high entrapment
      efficiency of 99.3%, TA-NE-F4 showed a fast dissolution rate of 80% in 10 min and
      100% in 20 min. The cytotoxicity of TA-NE-F4 against T24 human bladder cancer
      cells was 103.4-fold greater than TA alone in both a time- and a dose-dependent
      manner. Overall, we describe a feasible method for preparing TA-NEs that exhibit
      potent cytotoxicity.

PMID- 21870461
TI  - A new strategy for next generation sequencing: merging the Sanger's method and
      the sequencing by synthesis through replacing extension.
AB  - The present paper describes a feasible protocol enabling a merge of the classical
      Sanger sequencing method with the sequencing by DNA synthesis: The cycled
      proofreading sequencing. This new protocol involves partial chain termination and
      replacing extension. The first step is done with mixed ddNTP/dNTP targeting one
      type of nucleotide per subcycle and its relevant replacing extension with
      unlabeled phosphorothioate-modified dNTP of the same nucleotide type used in
      partial chain termination. Replacing extension serves as the key step to
      eliminate fluorescent signals integrated at the previous step, proofread errors,
      reactivate and synchronize the 3' termini of extended DNA molecules. This
      microchip-based sequencing method thus inherits advantages from "sequencing-by
      termination" and "sequencing-by-extension"; ddNTP is used and reactions are
      cycled. This microchip-based sequencing method is applicable for reaching the
      $1000-genome project goal.

PMID- 21870462
TI  - Intracellular magneto-spatial organization of magnetic organelles inside intact
      bacterial cells.
AB  - Magnetotactic bacteria naturally produce magnetosomes, i.e., biological membrane
      bound nanomagnets, at ambient conditions. It is important to understand
      simultaneously the possible size variations and the magnetic behavior of nano
      magnets inside intact bacterial cells for both applicational purposes as well as
      to enhance the basic understanding of biomineralization leading to intracellular
      nano-magnet synthesis. In this work, we utilize High-resolution Transmission
      Electron Microscopy and Near-field Scanning Optical Microscopy based measurements
      on intact non-fixed single cells to rigorously and quantitatively understand the
      intra-cellular magneto-spatial distribution of nano-magnets synthesized by
      Magnetospirillum gryphiswaldense. We demonstrate that it is possible to measure
      the relative magnetic moments along the intracellular magnetosomal chains for
      intact and non-fixed bacterial cells. Using our in vivo measurements on several
      single cells, we report that magnetic behavior of intracellular nano-magnets
      synthesized by magnetotactic bacteria depend on their relative location in the
      magnetosomal chains. Our work opens promising avenues in the direction of
      measuring the magnetic behavior of nano-magnets inside living systems by
      utilizing an operationally straight-forward approach.

PMID- 21870463
TI  - Sub acute toxicity assessment of glipizide engineered polymeric nanoparticles.
AB  - To our knowledge, no such polymeric nanoparticle formulation toxicity study has
      been reported for oral use. The oral route of drug administration is generally
      preferred because of its versatility, safety and relative patient comfort. Hence,
      there is an outstanding need of research for polymeric nanoparticles to find
      whether they are stable for prolonged shelf life, and yet have no toxicity when
      administered orally. The main objective of this study is to assess the safety of
      Glipizide (GZ) loaded polymeric nanoparticle systematically and to observe the
      toxic effects of nanoparticles on the functions of various tissues and organs in
      rats. The rats were randomly divided into 7 groups (6 in each group); viz. one
      normal control group (received saline), two groups (1:2 and 1:5 ratio of GZ
      Chitosan nanoparticle), two groups (1:2 and 1:5 ratio of GZ-Poly(methyl
      methacrylate) nanoparticle) and two groups (1:2 and 1:5 ratio of GZ-Ethyl
      Cellulose nanoparticle). After 30 days of nanoparticle administration, the blood
      haematology and biochemistry were investigated, along with the histopathological
      examination. The rats did not show any significant changes in all the parameters
      studied and the results clearly evidenced its safety. All formulations showed in
      vitro haemolytic activity less than 5%. Conclusion drawn from the present study
      is that the polymeric nanoparticles may be a suitable device for safe oral
      administration. A rigorous safety of these nanoparticles would enable their use
      in the field of diabetic therapy.

PMID- 21870464
TI  - Eudragit EPO nanoparticles: application in improving therapeutic efficacy and
      reducing ulcerogenicity of meloxicam on oral administration.
AB  - The objective of this investigation was to evaluate the potential of Eudragit EPO
      nanoparticles (EPO NP) in improving therapeutic efficacy of meloxicam (MLX). MLX
      loaded EPO NP were prepared by nanoprecipitation method and were characterized
      for particle size, encapsulation efficiency and for morphology. The in vitro
      dissolution profile of MLX loaded EPO NP and MLX suspension was evaluated. MLX
      loaded EPO NP had particle size of approximately 100 nm and the encapsulation
      efficiency of MLX was approximately 90%. The EPO NP significantly improved anti
      inflammatory activity of MLX (P < 0.01) as compared to that of MLX suspension.
      The enhanced anti-inflammatory effect was maintained for a longer duration (6 h)
      in case of MLX loaded EPO NP Oral administration of MLX loaded EPO NP also
      resulted in lesser ulcerogenicity as compared to that of MLX suspension
      indicating that nanoparticles can also decrease the adverse effects associated
      with MLX treatment.

PMID- 21870465
TI  - Nanoencapsulation improves the in vitro antioxidant activity of lipoic acid.
AB  - Lipoic acid is a widely studied substance, whose therapeutic effects are related
      to its antioxidant activity. Our objective was to develop lipoic acid-loaded
      lipid-core nanocapsules and evaluate their in vitro antioxidant effect against
      lipid peroxidation induced by ascorbyl free radicals, using soybean lecithin
      liposomes as the substrate. The nanocapsule suspensions were prepared by
      interfacial deposition of poly(epsilon-caprolactone) and characterized by
      particle size and polydispersion index (photon correlation spectroscopy), zeta
      potencial (eletrophoretic mobility), drug content and encapsulation efficiency
      (HPLC). The extent of lipid peroxidation was determined (TBARS). The
      nanostrucutures presented mean diameters of between 191 and 349 nm, zeta
      potential values from -14.1 +/- 4.5 to -10.4 +/- 0.6, and high lipoic acid
      encapsulation. A significant increase in the antioxidant activity of lipoic acid
      was achieved through nanoencapsulation or by increasing its concentration in the
      formulation. The protection results ranged from 48.9 +/- 3.4 to 57.4 +/- 9.1% for
      lipoic acid-loaded lipid-core nanocapsules. The lipoic acid release from
      nanostrucutures significantly decreased with increasing polymer concentration.
      Also, it was observed an increasing in the antioxidant activity as the lipoic
      acid release time decreased. The co-encapsulation of lipoic acid with melatonin
      in lipid-core nanocapsules did not improve the protection against lipid
      peroxidation. The results obtained demonstrate the optimal concentrations of
      polymer and lipoic acid in the formulations in terms of enhancing the antioxidant
      activity. Furthermore, by the strategy applied, it was verified that
      nanoencapsulation is an efficient alternative to increase the antioxidant effect
      of lipoic acid, representing a potential approach for therapeutic applications.

PMID- 21870466
TI  - Multimodal quantitative neuroimaging databases and methods: the Cuban Human Brain
      Mapping Project.
AB  - This article reviews the contributions of the Cuban Neuroscience Center to the
      evolution of the statistical parametric mapping (SPM) of quantitative Multimodal
      Neuroimages (qMN), from its inception to more recent work. Attention is limited
      to methods that compare individual qMN to normative databases (n/qMN). This
      evolution is described in three successive stages: (a) the development of one
      variant of normative topographical quantitative EEG (n/qEEG-top) which carries
      out statistical comparison of individual EEG spectral topographies with regard to
      a normative database--as part of the now popular SPM of brain descriptive
      parameters; (b) the development of n/qEEG tomography (n/qEEG-TOM), which employs
      brain electrical tomography (BET) to calculate voxelwise SPM maps of source
      spectral features with respect to a norm; (c) the development of a more general
      n/qMN by substituting EEG parameters with other neuroimaging descriptive
      parameters to obtain SPM maps. The study also describes the creation of Cuban
      normative databases, starting with the Cuban EEG database obtained in the early
      90s, and more recently, the Cuban Human Brain Mapping Project (CHBMP). This
      project has created a 240 subject database of the normal Cuban population,
      obtained from a population-based random sample, comprising clinical,
      neuropsychological, EEG, MRI and SPECT data for the same subjects. Examples of
      clinical studies using qMN are given and, more importantly, receiver operator
      characteristics (ROC) analyses of the different developments document a sustained
      effort to assess the clinical usefulness of the techniques.

PMID- 21870467
TI  - Improving Alzheimer's disease diagnosis with machine learning techniques.
AB  - There is not a specific test to diagnose Alzheimer's disease (AD). Its diagnosis
      should be based upon clinical history, neuropsychological and laboratory tests,
      neuroimaging and electroencephalography (EEG). Therefore, new approaches are
      necessary to enable earlier and more accurate diagnosis and to follow treatment
      results. In this study we used a Machine Learning (ML) technique, named Support
      Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD
      patients from controls. As a result, we developed a quantitative EEG (qEEG)
      processing method for automatic differentiation of patients with AD from normal
      individuals, as a complement to the diagnosis of probable dementia. We studied
      EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16
      probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4
      years. The results obtained from analysis of EEG epochs were accuracy 79.9% and
      sensitivity 83.2%. The analysis considering the diagnosis of each individual
      patient reached 87.0% accuracy and 91.7% sensitivity.

PMID- 21870468
TI  - The diagnostic value of clinical EEG in detecting abnormal synchronicity in panic
      disorder.
AB  - Electroencephalographic (EEG) findings repeatedly reported abnormal synchronous
      or even epileptiform discharges in panic disorder. Although less frequently
      occurring in patients with panic disorder, these deviant EEG features during
      panic attacks were also observed in intracranial EEG. For this purpose, our
      article reviews the consideration of abnormal synchronous neuronal activity in
      different neurocircuits, particularly limbic, as a suggested condition of panic
      attacks. Therapeutic approaches of anticonvulsants have shown reductions of
      symptoms and frequency of attacks in numerous patients suffering from panic
      disorder, supporting the presumption of underlying abnormal synchronous neuronal
      activity. Thus, scalp EEG recordings are still recommended for discovering
      indications of abnormal synchronous neuronal activity in panic patients.

PMID- 21870469
TI  - EEG complexity and attentional processes related to dissociative states.
AB  - Reported findings indicate that attentional narrowing is related to decreased
      complexity and increased inhibition of neural assemblies. These findings suggest
      that analysis of electroencephalogram (EEG) complexity could present a useful
      method for research of attentional changes related to dissociation. To examine
      this model we used a case study to test the two hypotheses: (1) that successful
      anticonvulsant medication would result in dissociative symptom alleviation,
      improvement of inhibitory neural functions, and decreased EEG complexity, and (2)
      that cognitive conflict, related to aversive events in the patient's past
      experience, during reliving of a dissociative state would lead to greater
      allocation of attention and decreased EEG complexity. Three EEG studies recorded
      in the eyes closed non-drowsy state were performed: (1) at baseline, (2) post
      induction of dissociative state, and (3) post-anticonvulsant medication following
      induction of dissociative state. A dissociative state was achieved following an
      interview regarding the patient's aversive past experiences through use of the
      Peritraumatic Dissociative Experiences Questionnaire (PDEQ). The patient's level
      of dissociation was measured using the Dissociative Experiences Scale-II (DES
      II). The PDEQ interview and DES-II assessment were also used one hour following
      the oral consumption of an anticonvulsant medication (clonazepam 2mg). Analysis
      of the data revealed that complexity values (PD2) are significantly lower
      following the oral consumption of clonazepam (2mg) in the majority of EEG
      channels. Additionally, complexity during the reliving of a dissociative state
      was statistically significantly lower than both the baseline and post-medication
      conditions in all but two EEG channels. Results of the case study suggest that
      changes in attentional processes linked to dissociation are related to: (1)
      decreased complexity when attention is extremely focused because of attentional
      narrowing to the disturbing past experience, and (2) increased complexity during
      ordinary experiences when attention is less narrowly focused.

PMID- 21870471
TI  - EEG theta and alpha reactivity on opening the eyes in the diagnosis of
      Alzheimer's disease.
AB  - The objective of this study was to evaluate the contribution of EEG theta and
      alpha reactivity on opening the eyes, in the diagnosis of slight and moderate
      Alzheimer's disease (AD). Thirty four patients with AD and a control group of 30
      individuals were studied, all being assessed using a neurological evaluation,
      CERAD neuropsychological battery (consortium to establish a registry for
      Alzheimer's disease), incorporating the Mini Mental State Examination (MMSE),
      Clinical Dementia Rating (CDR) and a qEEG analysis of the absolute band power at
      rest, with the eyes both open and closed. The theta and alpha reactivity indices
      were calculated on opening the eyes, defined from the relationship between the
      absolute powers in the respective bands in the periods with the eyes open and
      with them closed, the quotient of the relationship between the alpha and theta
      indices, the alpha/theta ratio, was also calculated. Multiple regression models
      were used to determine the accuracy in discriminating between the AD and control
      groups. A regression model using only cognitive data provided an accuracy of
      92.2%, whereas a regression model combining cognitive data and qEEG measurements
      provided an accuracy of 95.3% in the classification between AD and the controls.
      The variable for the qEEG was the left hemisphere alpha/theta index, since the
      other parameters were shown to be inferior with respect to the clinical data in
      the regression analysis. The integrated study of the theta and alpha reactivity
      indices on opening the eyes and the alpha/theta index, was shown to be a useful
      approach in qEEG in the evaluation of AD and should be evaluated with larger
      samples and with other data analysis methods, with the aim of increasing the
      accuracy.

PMID- 21870470
TI  - Utility of the electroencephalogram in attention deficit hyperactivity disorder.
AB  - An electroencephalogram (EEG) has not been routinely utilized in the evaluation
      of children with attention deficit hyperactivity disorder (ADHD). The utility of
      the EEG in ADHD is unclear. A recent study in our laboratory using sleep and
      sleep deprivation routinely found one in four non-epileptic children evaluated
      for attention deficit disorder has epileptiform discharges in the EEG, more than
      half focal. The majority of abnormalities (97.5%) occur in sleep and sleep
      deprived records compared to 7% in prior wake only records. A review of eight
      publications showed that laboratories using awake only as routine EEG recordings
      report a relatively low prevalence of epileptiform discharges, whereas the higher
      prevalence of epileptiform discharges is seen in those with more prolonged sleep
      recordings. We have determined that sleep deprivation and sleep are essential to
      rule out an abnormal EEG in attention deficit disorder. In patients with
      attention deficit disorder complicated by epilepsy, stimulant therapy is
      generally safe, provided seizures are controlled by antiepileptic medication.
      Patients with epilepsy or subclinical electrographic abnormalities not treated
      with anticonvulsants are at increased risk of seizures when stimulant therapy is
      introduced, especially extended-release methylphenidate. Apart from an increase
      in risk of seizures and need for caution in use of stimulants, studies show that
      epileptiform discharges in the electroencephalogram are linked to a better
      response of attention deficit to methylphenidate and a higher cognitive
      performance. Transient cognitive impairment related to subclinical electrographic
      abnormalities responds to antiepileptic medication. An EEG is important in
      selected cases of attention deficit disorder and is useful in choice of
      medication, especially in children with lack of awareness and transient cognitive
      impairment.

PMID- 21870472
TI  - Correlation between cognitive functions and nitric oxide levels in patients with
      dementia.
AB  - Dementia is defined as a clinical syndrome characterized by acquired loss of
      cognitive and emotional abilities, severe enough to interfere with daily
      functioning and quality of life. Event related potentials (ERP) are sensitive to
      task variables that relate to cognitive behavior. They might be altered in
      patients with disorders of cognition such as dementia. Application of the P300
      ERP component to the study of cognitive disorders provides a means of quantifying
      the level of mental impairment. At high levels, nitric oxide (NO), which is
      produced by microglia due to induction of nitric oxide synthase (NOS), is
      neurotoxic and may play a role in neurodegeneration. In our study an attempt has
      been made to record ERP in patients of mild and moderate dementia and to
      correlate their findings with nitric oxide levels in CSF and serum. Twenty
      patients with dementia were selected as cases and 20 subjects as controls, which
      were further subdivided according to the age groups. Both dementia cases and
      controls were assessed by minimental state examination (MMSE) and clinical
      dementia rating scale (CDRS) for evaluating the degree of dementia. It was
      observed that the MMSE score was reduced in demented cases. P300 latency was
      significantly delayed in mild and moderate cases of dementia. However, no change
      was seen in NO levels of cerebrospinal fluid (CSF) and serum in dementia cases
      and controls. A negative correlation was found between MMSE and P300 latency.
      Hence we conclude that cognitive impairment in demented patients is reflected in
      P300 latency but not in NO levels in CSF and serum.

PMID- 21870473
TI  - Obsessive compulsive disorder and the efficacy of qEEG-guided neurofeedback
      treatment: a case series.
AB  - While neurofeedback (NF) has been extensively studied in the treatment of many
      disorders, there have been only three published reports, by D.C. Hammond, on its
      clinical effects in the treatment of obsessive compulsive disorder (OCD). In this
      paper the efficacy of qEEG-guided NF for subjects with OCD was studied as a case
      series. The goal was to examine the clinical course of the OCD symptoms and
      assess the efficacy of qEEG guided NF training on clinical outcome measures.
      Thirty-six drug resistant subjects with OCD were assigned to 9-84 sessions of
      QEEG-guided NF treatment. Daily sessions lasted 60 minutes where 2 sessions with
      half-hour applications with a 30 minute rest given between sessions were
      conducted per day. Thirty-three out of 36 subjects who received NF training
      showed clinical improvement according to the Yale-Brown obsessive-compulsive
      scale (Y-BOCS). The Minnesota multiphasic inventory (MMPI) was administered
      before and after treatment to 17 of the subjects. The MMPI results showed
      significant improvements not only in OCD measures, but all of the MMPI scores
      showed a general decrease. Finally, according to the physicians' evaluation of
      the subjects using the clinical global impression scale (CGI), 33 of the 36
      subjects were rated as improved. Thirty-six of the subjects were followed for an
      average of 26 months after completing the study. According to follow-up
      interviews conducted with them and/or their family members 19 of the subjects
      maintained the improvements in their OCD symptoms. This study provides good
      evidence for the efficacy of NF treatment in OCD. The results of this study
      encourage further controlled research in this area.

PMID- 21870474
TI  - Tilt table testing with video EEG monitoring in the evaluation of patients with
      unexplained loss of consciousness.
AB  - It is well established that convulsive movements often accompany syncopal events
      yet many patients with these clinical features are misdiagnosed with seizures and
      often referred to epilepsy centers because they are refractory to treatment with
      anticonvulsant medications. Tilt table testing is the gold standard for
      diagnosing vasodepressor syncope, but it can fail to provide clinical details
      that help distinguish convulsive syncope from epileptic seizures and psychogenic
      events. This study evaluates the diagnostic utility of the addition of video and
      EEG monitoring during tilt table testing for patients with refractory episodes of
      unexplained loss of consciousness. Retrospective analysis was performed of 40
      consecutive patients who were referred to the Emory Epilepsy Center and underwent
      tilt table testing with concomitant video-EEG between March 1, 2007 and December
      1, 2008. EEG was recorded throughout the study in addition to video recording and
      single channel EKG. Events were classified as vasodepressor syncope, presyncope,
      or psychogenic. Tilt combined with video EEG was diagnostic in 26/40 (65%) of
      patients. Vasodepressor syncope was seen in 17/40 (42.5%), 9 of which had
      associated involuntary movements. Three patients experienced psychogenic non
      epileptic events. Antiepileptic drugs (AEDs) were being prescribed for 17
      patients, 7 of which were discontinued as a result of the testing. The majority
      of patients (38/40) had undergone prior neurological and cardiac evaluation with
      routine EEG, neuroimaging and/or Holter monitoring. Patients with convulsive
      syncope are often misdiagnosed and treated with AEDs despite prior
      neurodiagnostic and cardiac evaluation. Tilt table testing with video-EEG is
      useful in patients with refractory episodes of unexplained loss of consciousness
      and can avoid expensive non-diagnostic evaluations as well as ongoing treatment
      with unnecessary AEDs.

PMID- 21870475
TI  - Intractable epilepsy, audio-visual hallucinations and Charcot-Marie-Tooth disease
      1A in an African-American boy.
AB  - Charcot-Marie-Tooth disease 1A (CMT1A) is the most common autosomal dominant
      demyelinating sensorimotor polyneuropathy. A few patients with Charcot-Marie
      Tooth disease were reported in the literature to have epilepsy. We report on an
      African-American boy with CMT1A, with duplication of peripheral myelin protein 22
      gene, who also developed intractable generalized tonic-clonic seizures and
      audiovisual hallucinations.

PMID- 21870476
TI  - [Phytotherapy in combined treatment of chronic infection of the upper urinary
      tract in patients exposed to extracorporeal shock-wave lithotripsy].
AB  - Multicomponent biologically active additive Uroprofit made by Russian company
      Ecomir is used for phytotherapy of urolithiasis and urogenital infectious and
      inflammatory processes. Of 60 patients with urolithiasis and chronic
      pyelonephritis exposed to extracorporeal shock-wave lithotripsy (ECSWL), 30
      patients received additional anti-inflammatory therapy with Uroprofit. As shown
      by reduction of leukocyturia and crystalluria, increased 24-h diuresis in
      patients with urolithiasis after exposure to ECSWL, a positive effect was
      achieved on urethral inflammation. Thus, Uroprofit phytotherapy has
      antiinflammatory, diuretic, lithokinetic effects which makes it appropriate for
      treatment and prophylaxis of infectious-inflammatory process in the urethra.

PMID- 21870477
TI  - [Combined treatment of patients with nephrolithiasis complicated with secondary
      pyelonephritis].
AB  - A total of 151 patients with nephrolithiasis participated in the study of
      efficacy and safety of the drug prolit cepto in conservative treatment of
      nephrolithiasis patients, preoperative preparation and in postoperative period
      after extracorporeal shock-wave lithotripsy (EC-SWL) or nephrolitholapaxy. It was
      found that combined treatment of nephrolithiasis complicated by secondary
      pyelonephritis with addition of prolit cepto raises efficacy in management of
      inflammation due to a positive action on microcirculation and urine bacteria.
      Administration of prolit cepto in nephrolithiasis patients exposed to EC-SWL or
      nephrolitholapaxy reduces the risk of infectious and inflammatory complications,
      has a nephroprotective effect and improves the course of postoperative period.

PMID- 21870478
TI  - [Chronic cystitis in women of reproductive age].
AB  - The examination of 112 women suffering from chronic cystitis has detected
      frequent comorbidity of genital, gastrointestinal, locomotor and pelvic varicose
      diseases. Myofascial syndrome, hemodynamic disorders and venous congestion play a
      leading role in development of pain syndrome in women with comorbid diseases of
      the small pelvis organs. Clinicopsychological investigation of such women has
      revealed frequent vegetative and psychoemotional disorders with predominance of
      anxiodepressive conditions. Pain, dysuria and anxiodepressive disorders are among
      causes of imbalance of the autonomic nervous system which acvitaves regulatory
      systems and has an impact on quality of life. Women with chronic cystitis show
      significant deterioration of quality of life. Combined treatment including
      physical factors and therapeutic exercise reduced treatment duration, frequency
      of exacerbations, raised cost effectiveness.

PMID- 21870479
TI  - [The role of functional condition of pelvic inferior muscles and corticospinal
      tract in urination disorders in prostatic diseases].
AB  - The article analyses problems of diagnosis and treatment of neurogenic disorders
      of urination in the group of patients operated for prostatic pathology, the role
      of the conduction system of the corticospinal tract and conductive potential of
      perineal muscles in the above patients. Main standard electromyographic
      parameters were established by the data of examination of 7 controls--latency of
      the cortical and segmental evoked motor response, time of central motor
      conduction, amplitude of potentials of motor unities. Fifteen patients with
      prostatic diseases showed severe disorders of both corticospinal conduction and
      perineal muscular contraction. Patients with prostatic cancer or adenoma treated
      with different methods had denervation changes in pelvic inferior muscle in
      unaffected corticospinal conduction. Denervation changes after surgical treatment
      for prostatic cancer and delay of reinnervation, recovery of nervous control may
      be determined not only by the fact of operation but also by the course of the
      underling disease. Examination of the pelvic inferior muscles demonstrated that
      HIFU is a traumatic treatment of prostatic cancer because of extention of the
      physical impact beyond the prostate on muscular-nervous structures. These
      denervation muscular changes should be taken into consideration in assessment of
      the patient's condition and choice of treatment policy.

PMID- 21870480
TI  - [Correction of urodynamic disorders and quality of life in patients with
      prostatic adenoma after hyperthermia].
AB  - Prostatic adenoma gives rise to urodynamic disorders, affects not only sexual
      function and quality of men's life but also, indirectly, women's health. We have
      developed indications for concervative treatment of prostatic adenoma with
      transurethral radiowave hyperthermia (TRH). It was found that TRH has a positive
      early effect on a general somatic condition and prostatic function. Later, TRH
      improves working efficiency, emotional and social status of patients with
      prostatic adenoma and other parameters of their quality of life. TRH proved low
      traumatic, safe, it can be performed without anesthesiological aid.

PMID- 21870481
TI  - [A pharmacological cost-effective analysis of vobenzim use in combined treatment
      of chronic prostatitis].
AB  - A pharmacological cost-effective analysis of systemic enzymotherapy combination
      with fluoroquinolone antibiotics in the treatment of chronic bacterial
      prostatitis showed cost-effect of such therapy: medical cost efficacy of the
      treatment of chronic bacterial prostatitis with antibiotic + vobenzim is 2 times
      higher than of antibiotic treatment only.

PMID- 21870482
TI  - [Transurethral contact electroimpulse ureteropyelolithotripsy].
AB  - Transurethral contact electroimpulse ureteropyelolithotripsy (TCEUT) was
      conducted in 161 patients aged 18 to 84 years (mean age 47 +/- 14 years) admitted
      to the urological department of Zhukovsky city hospital in 2006-2009. Female/male
      proportion 1.4:1. Overall efficacy of TCEUT was 98%, the concrement was
      destructed completely during the first TCEUT session in 98%, partially in 2%
      cases. The method was feasible in all the patients if the instrument could reach
      the concrement. Duration of the session providing complete elimination of the
      concrements varied from 1 to 6 months.Contact electroimpulse ureterolithotripsy
      is conducted with single impulses beginning with low energy (0.45 J). Contact
      electroimpulse pyelolithotripsy requires a higher initial impulse energy (0.6 J).
      TCEUT is a highly effective method of the treatment of concrements of the upper
      urinary tract. Side effects were registered in maximum 5%. Long-term existence of
      the concrement in the urinary system raises the risk of intraoperative
      complications.

PMID- 21870483
TI  - [Laparoscopic and retroperitoneoscopic resection of the kidney].
AB  - The surgeons of the clinic at the chair of endoscopic urology operated 32
      patients (18 males, 14 females, age 40-78, mean age 55 +/- 0.8 years) with renal
      carcinoma (RC) from 2007 to 2010: 31 patients had RC stageT1N0M0, 1 patient-
      T2N0M0, 12 patients had RC of the right kidney, 19--of the left kidney, bilateral
      RC was in 1 patient. A laparoscopic transperitoneal approach was used in 14
      cases. Indications for such approach were the following: size of the tumor 2.2-4
      cm, location of the tumor in the upper anterior segment (n = 13), in the middle
      segment (n = 1). Ischemia was made in 5 patients. Resection of the kidney via a
      laparoscopic retroperitoneal approach was made in 11 patients. Indications were
      the following: size of the tumor 1.1-4 cm, posterior tumor location. Ischemia (17
      and 24 min) was used in 2 cases, mean blood loss 118 ml (from 50 to 250 ml). Nine
      patients were operated with application of YAG:Nd laser (Lazurit) which resected
      an extraorganic tumor of a small size (1.1-2.2 cm) without ischemia and
      significant blood loss. Laparoscopic assisted resection of the kidney was
      performed in 9 cases. Hand assistance was indicated in large tumors (4.3 to 8.9
      cm), posterior tumor location (n = 4), upper location (n = 2). One-stage
      bilateral resection of the kidneys in the middle segment was made in one patient.
      Hand assistance was also required in one patient for one-stage resection of two
      tumors of the right kidney. Laparoscopic resection of the kidney is indicated in
      bilateral tumor, in a single functioning kidney, in affection of the
      contralateral kidney, or disease with potential contralateral kidney affection.
      Indications for endovideosurgical methods of treatment need detailed
      specification and perfection. Choice of one of the above approaches should be
      based on tumor size and its location.

PMID- 21870485
TI  - [Ureteral injury caused by an intrauterine loop].

PMID- 21870484
TI  - [Program "reproductive health of boys" in Samara region].
AB  - Because of great importance of early detection of urological pathology in boys,
      we made a prophylactic examination of boys aged 2-17 years. Pediatric urologists
      andrologists examined 20402 boys for 2008-2009. They detected: diseases of the
      penis (11.1%), of the testicles (6%), anomalies of the kidneys (2.5%), urinary
      diseases (2.6%). The above urological problems can be corrected with good
      prospects for reproductive health of the examinees.

PMID- 21870486
TI  - [Treatment of idiopathic retroperitoneal fibrosis].

PMID- 21870487
TI  - [Penile fracture].

PMID- 21870488
TI  - [Proteometabolic analysis in urology].

PMID- 21870489
TI  - [Urethral amyloidosis].

PMID- 21870490
TI  - [Mechanism of malate dehydrogenase isoform formation in Sphaerotilus natans D-507
      under different cultivation conditions].
AB  - Electrophoretically homogenous preparations of malate dehydrogenase (MDH)
      isoforms of the bacteria Sphaerotilus natans D-507 with specific activity 7.46
      U/mg and 5.74 U/mg with respect to protein concentration have been obtained. The
      dimeric isoform of the enzyme was shown to function under organotrophic growth
      conditions, whereas the tetrameric isoform was induced under mixotrophic
      cultivation conditions. PCR-analysis revealed a single gene encoding the malate
      dehydrogenase molecule. The topography of the MDH isoform surface was studied by
      atomic-force microscopy, and a 3D-structure of the enzyme was obtained.
      Spectraphotometric analysis data allowed us to suggest that stabilization of the
      tetrameric form of MDH is due to additional bounds implicated in the quaternary
      structure formation.

PMID- 21870491
TI  - [Longicorn beetles (Coleoptera:Cerambycidae) differ considerably in the degree of
      their mushroom body development].
AB  - A duality in the general structure of the mushroom body in longicorn beetles is
      confirmed. This duality is associated with the fact that they are formed by two
      solitary neuroblasts or two neuroblast clusters on each side of the brain and are
      manifested as a bipartite structure of both the calyx, which is the main sensory
      input, and the peduncular apparatus. Within the studied longicorn beetles,
      modifications in the general structure of mushroom bodies have been found; these
      modifications are caused by two oppositely directed morphogenetic processes,
      namely, the concentration of structures and their compartmentalization. The
      concentration leads to disappearance of the bipartite structure of the peduncular
      apparatus, whereas compartmentalization leads to a secondary subdivision of these
      structures into anatomically distinct subsections. This process is most
      pronounced in the peduncle and lobes. The mushroom bodies are best developed and
      differentiated in the members of the subfamily Lamiinae.

PMID- 21870492
TI  - [The monogamous reproductive strategy in lepidoptera].
AB  - On the basis of literary sources and experimental data, the advantages of a
      monogamous reproductive strategy are analyzed. Monogamous species of Lepidoptera
      have no postcopulative mechanisms of control over the success of reproductive
      sperm competition, cryptic female choice, and, probably, the male's nuptial gift.
      Selection of the sex partner and of the quality of the future generation is
      determined by the precopulative and copulative mechanisms of the reproductive
      behavior, which include chemocommunication and a "lock-and-key" mechanism. In an
      experiment with one male and one female, the quota of successful mating can
      depend on the morphological complication of the genital apparatus of males. Cases
      are considered of repeated mating for some, usually monogamous, species. In
      comparison with the variant of the experiment with one male x one female, the
      frequency of repeated mating increases with the addition of two males to one
      female but decreases in the presence of two females with one male. A possible
      reason for the appearance of repeated mating may be the weight of the insect's
      body exceeding the average.

PMID- 21870493
TI  - [Peculiarities of the contour feather microstructure in the Corvidae family].
AB  - The results of comparative electron microscope study of the fine structure of the
      definitive contour feathers often Crows species (Perisoreus infaustus, Garrulus
      glandarius, Cyanopica cyanus, Pica Pica, Podoceus panderi, Nucifraga
      caryocatactes, Corvus monedula, C. frugilegus, C. cornix, C. corax) are
      presented. The results of the research allowed us to conclude that crows, along
      with the traditional elements of feather architectonics, have a number of species
      specific microstructure characteristics that are taxonomically important.

PMID- 21870494
TI  - [Isolating structures of gerbils' digestive tract (Gerbillidae, Rhombomys,
      Meriones) and their functional significance].
AB  - The morphology of the digestive tract of three species of gerbils, characterized
      by different food specialization-Rhombomys opimus, Meriones tamariscinus and M.
      meridianus--is considered. The correlation between areas of glandular and
      keratinizing epithelium is variable and depends greatly on the type of stomach
      filling and distribution of food mass in it. The bordering fold and
      ileocecaljunction is not only able to isolate the forestomach and caecum
      significantly but also may be a mechanism of regulation of food movement through
      the digestive tract. The close location of ileum's opening to the caecum and its
      outlet to the colon, as well as isolation of caecum's cavity by a circular fold,
      could provide direct food transit from the ileum to the colon.

PMID- 21870495
TI  - [Glutathione-S-transferase as a molecular biomarker of the state of marine
      organisms influenced by anthropogenic pressure].
AB  - The activity ofglutathione-S-transferase (GST), a key phase II enzyme catalyzing
      the biotransformation of organic electrophilic compounds, was studied in the
      bivalve Crenomytilus grayanus, the mysid shrimp Neomysis mirabilis, and the
      flounder Liopsetta pinnifasciata from Peter the Great Bay, Sea of Japan. GST
      activity was increased in fish and mollusks from polluted areas of the bay,
      compared to background areas. In mysid shrimps, pollution caused inhibition of
      the activity of this enzyme. The role of GST in adaptation processes of different
      species to the current level of pollution is discussed.

PMID- 21870496
TI  - [Distribution of Euphausiid and Decapod larvae in the spring plankton of the
      southern Barents Sea].
AB  - New data have been obtained on the spatial distribution of the early
      developmental stages of Malacostraca in the mesozooplankton of the southern
      Barents Sea. In spring 2007, the euphausiid stages with the highest abundance
      (over 80%) were eggs and nauplii. Decapod larvae were represented by zoeae of
      Paralithodes camtschaticus, Paguruspubescens, and Hyas araneus; their abundance
      was at most 1.5% of total zooplankton abundance. The larvaton groups dominant by
      abundance were furciliae of Euphasiacea (14.5 +/- 6.2 mg/m3) and zoeae of P.
      camtschaticus (32.7 +/- 15.9 mg/m3). The size structure of larval hemipopulations
      was similar over the studied water area. Comparison with data on the larval body
      length obtained in other areas of the sea leads to a conclusion on the
      independence of the decapod groups of Eastern and Western Murman.

PMID- 21870497
TI  - [Testate amoebas of pine forests in Mexico].
AB  - The population of testate amoebas in the soils of pine forests in Mexico has been
      studied. In total, 68 species, varieties, and types of testate amoebas with
      cosmopolite distribution were found. The species diversity of the testate
      population includes hygrophilous species that differ from hygrophilous species
      with luvisols in higher andosols. Comparative analysis using the results of one
      available study of soil testate amoebas from Mexico has been carried out [Bonnet,
      1977].

PMID- 21870498
TI  - [Geographic distribution features of subgenus and life forms of Lymnaeidae
      (Gastropoda, Pulmonata) in Eastern Europe].
AB  - Relative species richness as a ratio of species number known from the teritory
      norther than polar circle and species number in Eastern Europe as a whole was
      calculated from all subgenuses and life forms of the Lymnaeidae. The largest
      value of this character typical for amla-like life form. The dominance of one
      life form is a result of its adaptation to life in places with wave activity and
      for water respiration. Large relative species richness of subgenuses Lymnaea and
      Peregriana is a sequence of ampla-like life form dominance, wuch consist from
      these subgenuses.

PMID- 21870499
TI  - [Basic features of the nemoral curculionid-beetle fauna (Coleoptera,
      Curculionoidea) from eastern Europe and Western Siberia].
AB  - There are 132 curculionids associated with deciduous trees in eastern Europe and
      western Siberia. The weevils and bark beetles make up the basis of the fauna,
      forming almost 80%. The fauna of oak is the richest (64 species). The species
      composition on the ash-tree (50% are monophages) is highly original.
      Impoverishment of the species composition from the west to the east is revealed.
      The fauna declines by 18% from 45 to 550 E. The species composition reduces two
      times beyond the Urals. The faunal boundaries are revealed from west to east and
      from east to west. The most significant boundary (47% of the fauna do not pass
      it) for distribution of species to the east is situated between 40 and 45 degrees
      E. Two significant faunal boundaries are revealed from south to north. The fauna
      of curculionids of deciduous trees is formed by four groups of species. The
      southern European species (54%) and western palaearctic species (40%) dominate.
      The species composition of the studied territory is similar to the fauna of
      Middle Europe. Formation of the modern fauna of curculionids of deciduous trees
      in eastern Europe probably occurred in the Holocene. The western Palaearctic and
      Transpalaearctic species could have occupied the considered territory since the
      Late Pleistocene. Southern European species appeared in the considered territory
      after the Valdai glaciation during the warming in the Atlantic period of the
      Holocene. Penetration of East Palaearctic species began rather recently (last few
      decades), probably due to climate warming and economic activities.

PMID- 21870501
TI  - [The comparative analysis of extra- and intracellular proteasomes from K562 cell
      line].
AB  - The comparative analysis of peptidase activities of extra- and intracellular
      proteasomes was carried out. Here we have shown that excreted proteasomes exhibit
      higher chymotrypsin-type and lower tripsin-like peptidase activities that
      cytoplasmic particles. Posttranslational modifications (PTMs) of 20S proteasomal
      subunits were revealed by immunoblotting techniques. We have observed the
      difference in PTMs of associated with enzymatic activities subunits beta2, beta5
      and beta5 of extracellular and cytoplasmic proteasomes. Proteasomal subunits
      alpha2, 4, 7 and beta7 also had a variety of PTMs. The phosphorylation level of
      excreted proteasomes was lower compared to that of the intracellular ones. This
      observation strongly suggests the involvement of this PTM in the regulation of
      proteasomes excretion from cells.

PMID- 21870502
TI  - [Alteration of brown adipocyte Ca2+ responses in culture by adrenergic
      activation].
AB  - Thermogenic capability of brown adipose tissue is controlled by norepinephrine.
      Interaction of norepinephrine with adipocyte at- and P3-adrenergic receptors
      results in the increase of Ca2+ and cAMP concentrations. The [Ca2+]i changes
      initiated by norepinephrine and selective agonists of alpha1- and beta-adrenergic
      receptors, cirazolin and isoproterenol, were recorded in single cells of primary
      culture on the 1st, 3rd and 6th days in vitro. On the first day, isoproterenol
      induced [Ca2+]i changes as compared to cirazolin-induced ones were characterized
      by greater amplitude and lesser impulse duration over the entire range of
      physiological concentrations used. These differences were negligible after 3 days
      and kinetic differences were practically absent after 6 days of cultivation. The
      agonist-induced [Ca2+]i changes in proliferating and differentiated cells
      differed significantly: in the process of cell growth in culture, the amplitude
      of calcium response increased, the duration of impulse signal decreased and the
      sensitivity to adrenergic agonists increased. The Ca2+ store in endoplasmic
      reticulum increased during the cell growth and development in culture, according
      to thapsigargin-induced Ca2+ response amplitude increase in Ca2+ free medium. The
      rate of Ca2+ pumping out of cell characterizing PMCA-activity also increased.

PMID- 21870503
TI  - [Regulatory volume increase (RVI) and apoptotic volume decrease (AVD) in U937
      cells placed into hyperosmotic medium].
AB  - Time course of changes in intracellular water, K+ and Na+ of U937 cells incubated
      in hyperosmolar medium with addition of 200 mM sucrose was studied. Ouabain
      sensitive and ouabain-resistant Rb+ (K+) influxes were measured during regulatory
      cell volume increase (RVI) and apoptotic volume decrease (AVD). Microscopy of
      cells stained by Acrydine orange, Ethydium bromide, APOPercenrage Dye and
      polycaspase marker FLICA was performed. We found that initial osmotic cell
      shrinkage induced both RVI and AVD responses. RVI dominated at the early stage
      whereas AVD prevailed at the later stage. In view of the data obtained in U937
      cells the current opinion that RVI "dysfunction" is a prerequisite for apoptosis
      and AVD (Subramanyam et al., 2010) should be revised. U937 cells are capable to
      trigger of apoptosis and AVD in spite of the unimpaired RVI response. It is
      concluded that AVD plays a significant role in preventing osmotic lysis of
      apoptotic cells rather than in the initiation of apoptosis.

PMID- 21870504
TI  - Biological and morphological characterization of in vitro expanded human muscle
      derived stem cells.
AB  - Stem cells are generally characterised as clonogenic and undifferentiated cells
      with the capacity of self-renewal and plasticity. Over the past few years, the
      adult stem cells have been derived from various types of tissues including the
      skeletal muscle. The main goal of the present study was the isolation, in vitro
      expansion and characterisation of muscle-derived stem cells (MDSCs). Thereby
      obtained results showed that MDSCs have a fibroblast-like shape with a large
      nucleus having one to four nucleoli. The cytoplasm was transparent without any
      signs of vacuolisation. TEM analysis showed an ultrastructure of cells with high
      proteosynthetic activity. MDSCs had a large and irregular nucleus with variable
      number of nucleoli. The cytoplasm contained a richly developed and rough
      endoplasmic reticulum, prominent Golgi apparatus cisterns as well as transport
      vesicles containing glycogen granules and variable microvilli and filopodia. They
      expressed alpha-actin and desmin. Results of the phenotypic characterization
      showed that the analyzed cells were positive for CD29, CD34, CD44, CD90, CD105
      and HLA Class I. They did not express CD14, CD45, CD235a, HLA Class II and human
      fibroblast surface protein. According to these results it should be emphasised
      that MDSCs after performing the detailed studies focused on their immunological
      properties and differentiation potential may be used in the cell therapy of many
      degenerative diseases.

PMID- 21870505
TI  - [Multidrug resistance P-glycoprotein inhibits the antiapoptotic action of
      mitochondria-targeted antioxidant SkQR1].
AB  - Mitochondria-targeted antioxidants of the SkQR1 family, being accumulated in
      energized mitochondria, protect cells from oxidative stress by increasing the
      level of reduced glutathione and decreasing the cell-damaging effect induced by
      hydrogen peroxide. Using various human transformed cell lines and SkQR1 (a
      fluorescent member of the SkQ family), we show that SkQRI is ejected from
      chemotherapy-resistant cells by P-glycoprotein - one of the main transport
      proteins determining multidrug resistance typical for many neoplastic cells. It
      is also shown that SkQR1 ejection is neutralized by P-glycoprotein inhibitors
      (verapamil and pluronic L61). In experiments on K562 cells, it was found that the
      subline sensitive to chemotherapy is protected by SkQRI from apoptotic action of
      hydrogen peroxide. Protection of the resistant subline occurs only after
      inhibition of P-glycoprotein.

PMID- 21870506
TI  - [The comparative characteristic seratonergic neurons in some nucleus of the
      oblong brain of the rat].
AB  - Immunohistochemistry in Wistar rats identified serotonergic neurons in 8 cores of
      the medulla oblongata belonging to the so-called "bulbar vasomotor center". Using
      morphometry revealed that the proportion of serotonergic neurons located in the
      projection of the cores studied ranged from 17 to 26 %, and value of the index
      rised to 34-40 % only in the cores of the back seam. Single immunopositive cells
      that can perform the integrative function in the regulation ofhemodynamics were
      detected between the cores as well as between the cores and pathways.

PMID- 21870507
TI  - [Adult human retinal pigment epithelial cells - a potential source of cells for
      regeneration retina].
AB  - Retinal pigment epithelium (RPE) arises from neuroectoderm and plays a key role
      in support of photoreceptor functions. Several degenerative eye diseases, such as
      macular degeneration or retinitis pigmentosa, are associated with impaired RPE
      function that may lead to photoreceptor loss and blindness. RPE cell culture
      derived from adult human eyes autopsy could be an important source for
      transplantation to cure such retinal degenerative diseases. RPE cells subsequent
      isolation and maintenance in culture are described. Besides the results of
      immunocytochemical analysis that characterizes dedifferentiated state of cultured
      adult human RPE cells are given. Our findings demonstrate that mature human RPE
      cells have the capacity to express neural markers in response to conditions that
      promote dedifferentiation.

PMID- 21870508
TI  - [Localization of the Dras1 sequence to polytene chromosomes in sibling species of
      the Drosophila virilis group].
AB  - Drasl gene was mapped by in situ hybridization to polytene chromosomes of several
      sibling species of the Drosophila virilis group and hybrids between them. A 1037
      bp fragment of the Drasl gene of the D. virilis genome was used as a probe. The
      gene sequence is localized to the region of the disk 25 A-B on the chromosome 2
      of the polytene chromosome map of D. virilis.

PMID- 21870509
TI  - [Patterns of transposable elements distribution on the Drosophila melanogaster
      polytene chromosomes before and after selection for a quantitative trait].
AB  - The effect of selection for radius vein length on the distribution of
      hybridization sites of the P and hobo transposons and the mdgl and mdg2
      retrotransposons on polytene chromosomes of Drosophila melanogaster salivary
      glands was studied. The patterns of these transposable elements (TEs)
      distribution were polymorphic in both the parental strain and selected strains.
      The similarity in mdg1 and mdg2 patterns between strains selected in one
      direction was closer than between strains selected in opposite directions, but
      the selected strains were closer to each other than to the parental strain
      regardless of selection direction. No mdg2 hybridization sites that would be
      absent in the control were found in the selected strains. There were more mdg2
      and hobo hybridization sites in the strains selected in the (+) direction than in
      the (-) direction. The mobility of hobo copies in the strains studied correlated
      with the presence of its full-sized copy in the genome. The polymorphism of all
      TEs studied except for mdgl was greater for strains selected in the (+) direction
      that in the (-) direction. These facts suggest that some TEs migrate over the
      genome independently of selection, and others are markers of evolutionary events
      rather than their causes.

PMID- 21870510
TI  - [Fibrillar actin in the nuclear apparatus of the ciliate Paramecium caudatum].
AB  - Due to their nuclear dualism, ciliates provide a good model for studying the role
      of actin in spatial organization and transcription activity of the nucleus. The
      actin in the nuclear apparatus of the ciliate Paramecium caudatum was studied
      using fluorescently labeled phalloiodin and indirect immunocytochemistry.
      Fibrillar actin was demonstrated in both of the nuclei. Actin was revealed in the
      chromatin areas, and was often associated with the periphery of the amplified
      nucleoli in the macronucleus. Redistribution of actin was observed depending on
      different physiological state of the cells. Stable infection of the macronulear
      with the intranuclear endobionts Holospora obtuse led to the loss of nuclear
      actin accompanied by significant nuclear fragility and redistribution of the
      phosphorylated form of the actin-binding protein cofilin. Spherical bodies
      resembling karyosphere were found in the macronuclear anlagen.

PMID- 21870511
TI  - [Effect of acetylcholine and acetylcholinesterase on the activity of contractile
      vacuole of Amoeba proteus].
AB  - Acetylcholine (ACh, 1 microM) stimulates activity of the contractile vacuole of
      proteus. The effect of ACh is not mimicked by its analogs which are not
      hydrolyzed by acetylcholinesterase (AChE), i. e., carbacholine and 5
      methylfurmethide. The effect of ACh is not sensitive to the blocking action of M
      cholinolytics, atropine and mytolone, but is suppressed by N-cholinolytic,
      tubocurarine. The inhibitors of AChE, eserine (0.01 microM) and armine (0.1
      microM), suppress the effect of ACh on amoeba contractile vacuole. ACh does not
      affect activation of contractile vacuole induced by arginine-vasopressin (1
      microM), but it blocks such effect of opiate receptors agonist, dynorphin A1-13
      (0.01 microM). This effect of ACh is also suppressed by the inhibitors of AChE.
      These results suggest that, in the above-described effects of ACh, AChE acts not
      as an antagonist, but rather as a synergist.

PMID- 21870512
TI  - [The mitochondrial membrane potential and oxygen consumption in the heart of
      spontaneously hypertensive rats].
AB  - We investigated the mitochondrial membrane potential and processes of respiration
      and oxidative phosphorylation in suspension of cardiac mitochondria from 6 month
      old spontaneously hypertensive rats (SHR) and Wistar (as a control) male rats.
      The mitochondrial membrane potential and the speed of oxygen consumption were
      measured using the method described by M.Brand (1995). Processes of respiration
      and oxidative phosphorylation in cardiac mitochondria were measured using
      Oxygraph (Hansatech instruments, Norfolk, England). It has been found that in SHR
      the mitochondrial membrane potential was lower (-113.76 mV+/-3.65 mV) compared to
      Wistar rats (DeltaPsim=-152.85 mV+/-13.52 mV, p<0.01). In SHR, the respiration
      rate in state V2 by Chance and V3 were increased compared to Wistar rats
      (p<0.001). The respiration control by Chance was depressed by 23.9% in SHR
      compared to Wistar rats. Our data demonstrate, that SHR have some features of
      functioning of cardiac mitochondria which distinguish them from the Wistar rats.
      Our data suggest a functional link between mitochondrial energy supply and
      arterial hypertension.

PMID- 21870513
TI  - [Insulin resistance and physical performance in middle age and elderly people].
AB  - In 43 middle age and elderly people without obesity (body mass index of less than
      30 kg/m2) we studied the relationship between insulin resistance (IR) and
      physical performance. It is shown that in healthy elderly IR is associated with a
      moderate increase of insulin and a small increase in the level of glucose in the
      blood plasma. In the middle age people, IR has no effect on physical performance.
      IR in the elderly people is accompanied by the decrease in physical performance
      due to less economical for hemodynamic load and oxygen consumption. A lower
      exercise tolerance in elderly people without obesity can be considered not only
      as a risk factor for insulin resistance, but also as its consequence.

PMID- 21870514
TI  - [The frequency of allelic polymorphism of matrix Gla-protein gene in acute
      coronary syndrome patients].
AB  - Allelic polymorphisms of matrix Gla protein (MGP) gene were determinated in 115
      patients with acute coronary syndrome (ACS) and in 110 practically healthy
      people. It was shown that interrelation of major homozygotes, heterozygotes and
      minor homozygotes by T-138-->C MGP promoter polymorphism in patients with ACS
      were 59.8%, 32.7%, 7.5% and in control 58.7%, 36.7%, 4.6% (P>0.05 by X2-test); by
      G-7-->A polymorphism: 42.1%, 45.6%, 12.3% and 41.8%, 54.5%, 3.6% correspondingly
      (P<0.05); and by Thr83Ala exon 4 polymorphism: 42.6%, 43.5%, 13.9% compared to
      43.9%, 45.9%, 10.2% in control (P>0.05). The obtained data show that MGP A/A
      variant of MGP promoter G-7-->A polymorphism is a risk factor of ACS in Ukrainian
      population. These data indicate also that the intensity of calcification
      influences atherosclerotic injury of coronary artery.

PMID- 21870515
TI  - [Changes in calcium-dependent potassium channels of isolated smooth muscle cells
      of the bladder in rats with experimental diabetes].
AB  - Activation of large conductance Ca2+-dependent potassium channels (BK channels)
      influences repolarization of the action potential and the level of the resting
      potential of detrusor smooth muscle cells (SMC). Overactive bladder syndrome
      (OBS) is one of the complications of diabetes. Here using whole-cell patch clamp
      technique we show sizable reduction of depolarization-evoked BK current (lBK) and
      decrease in the amplitude and frequency of spontaneous transient outward currents
      (STOCs) in isolated SMC from detrusor of rats with streptozocin-induced diabetes
      compared to control animals. Under the diabetes IBK density at step
      depolarization to +50 mV decreased from control value of 15.0+/-0.4 pA/pF to
      10.0+/-0.5 pA/pF, whereas the mean values of the STOCs' frequency and amplitude
      at holding potential -20 mV were reduced from 12.0+/-1.5 Hz to 2.4+/-0.6 Hz and
      from 0.9+/-0.1 pA/pF to 0.510.1 pA/pF, respectively. Using real time RT-PCR it
      was found that the expression of mRNA for the BK-channel primary pore-forming
      KCa1.1-subunit increases under the diabetes, whilst that for the auxiliary
      BKCabeta1-subunit decreases. It is concluded that the observed changes in the BK
      channel currents can enhance excitability of the detrusor SMCs thereby promoting
      myogenic OBS. However, further studies are needed to determine how the decrease
      in BKCabeta1 expression under the diabetes impairs functional properties of BK
      channels and to establish possible changes in calcium signals that modulate
      channel activation.

PMID- 21870517
TI  - [The influence of calcitonin on the liver secretory function in rats].
AB  - The influence of calcitonin on the choleresis level and bile acids spectrum was
      investigated in acute experiments on the rats with common biliary duct
      cannulated. We determined the intensity of bile secretion during 3 hours and
      quantitative content of conjugated and free bile acids using thin-layer
      chromatography. It was shown that intramuscular introduction of synthetic salmon
      calcitonin (200 ng/kg) increases the secreted bile volume and the content of
      conjugated bile acids in the bile. The administration of salmon calcitonin
      resulted in increase of bile volume (+17.4% (P<0.05)), taurotrihydroxycholates
      (+58,3% (P<.001)), taurodihydroxycholates (+68.5% (P<0.01)),
      glycodihydroxycholates (+120.8% (P<0.01)), while the total content of free bile
      acids was not significantly altered as compared with control. At the same time,
      under the hormone influence we observed bile acid spectrum redistribution and a
      part of conjugated cholates increased against a decreasing of free bile acids
      part. The present results suggest that the salmon calcitonin intensifies the
      processes of conjugation of bile acids with amino acids taurine and glycine in
      hepatocytes and canalicular secretion that results in improvement of
      solubilization properties of the bile, ability of the bile to hold cholesterol in
      solute state and prevent the formation of calculi in biliary tracts.

PMID- 21870516
TI  - [Heart rhythm in humans with different processing levels of acoustic
      information].
AB  - The peculiarities of the heart rhythm regulation were investigated in humans
      during the processing of acoustic information. Statistically significant
      differences were found in individuals with different levels of auditory-motor
      reactions according to the heart rhythm characteristics. Individuals with the
      high level of reactions were characterized by significantly lower total power
      spectrum (TP=1276.2 ms2), by the power spectrum of high (HL=280.1 ms12) and very
      low frequencies (VLF-469.8 ms2), as well as by low indexes of standard deviation
      of R-R intervals (SDNN=37.4 ms), when compared with the persons with the low
      level of reactions (5248.8; 866.7; 1937.0; 69.8 ms2). The correlation analysis
      confirmed the dif- ferences between the groups ol persons with adtierent number
      of processed information and variable (r=0.41, P<0.05) and spectral
      characteristics of heart rate (r=-0.49--0.56, P<0.05). Different strategies of
      activation of non-specific brain systems in formation of psycho-physiological
      reactions and participation of heart rhythm regulatory mechanisms in vegetative
      support of auditory information processing are discussed.

PMID- 21870518
TI  - [Effect of 1,5-benzodiazepine derivatives on the electrical activity of neurons
      of the Helix albescens Rossm].
AB  - Using a standard technique for intracellular recording of potentials, we
      investigated the influence of two new derivatives of 1,5-benzodiazepine-2-one on
      the electrical activity of neurons of the Helix albescens Rossm. These substances
      possess neurotropic properties, the effects were concentration dependent in the
      concentration range 10(-6) M -10(-2) and did not depend on the type of neurons.
      We defined the threshold, optimum and toxic concentrations for the compounds
      investigared. Analysis of the total ion current showed that the compounds reduce
      the rate of inward Na+- and Ca2+ currents and of outward K+-currents.

PMID- 21870519
TI  - [Changes of NO-ergic activity in the salivary glands of rats under conditions of
      omeprazole-induced hypergastrinemia].
AB  - Under conditions of omeprazole-induced hypergastrinemia the activity of NOS and
      the concentration of NO2-, the end product of metabolism of nitric oxide were
      studied in salivary glands of rats. We detected an increase in NOS activity,
      reaching a maximum (7.61+/-0.39 Mmol [NO2-]/(g*min) at 14th day of the
      experiment. At 28th day following omeprazole introduction its activity was 5,76+/
      0.25 Mmol [NO2-]/(g*min).

PMID- 21870520
TI  - [Altered collagene characteristics and lysyl oxidase activity in lathyrism].
AB  - Experiments were carried out on rats with lathyrism, which was induced by adding
      semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a
      30% reduction in the body weight and an increase in.organ weight coefficients.
      Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue
      degradation, cartilage growth, 46% decrease of the calcium level in the femur. It
      has been detected essential structural changes in extracellular matrix based on
      the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme
      for the collagen development, showed 5-fold decrease in the aorta tissues. The
      level of formaldehyde, a nonenzymic cross-links developer, has been measured in
      the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione)
      administration and then fluorimetric determination of formaldimedone. Under
      semicarbazide load, the formaldehyde level in the liver tissue was reduced by
      47%. Therefore, semicarbazide influences not only the enzymic development of
      aldehyde groups in collagen, but the level of other aldehydes, which can cause
      cross-links. This experimental model of lathyrism is appropriate for
      investigation of the lysyl oxidase inhibitors effect on extracellular matrix.

PMID- 21870521
TI  - [Use of mathematical models in study of nitric oxide, myoglobin and cell oxygen
      regimen].
AB  - The influence ofnanomolar concentrations of NO on oxygen regimen of muscle cells
      was investigated. The intracellular distribution of oxygen consumption rates,
      pO2, NO and myoglobin was calculated by mathematical modeling of diffusion
      reactions of O2, NO and myoglobin in the muscle cell. The diffusion of O2, and NO
      from blood vessel surface into cell was taken into account. According to
      calculations, NO roughly regulates the oxygen regimen of cell, because it
      increases the tissue pO2 level by inhibition of mitochondria activity in the
      whole cell space. The presence ofmyoglobin is capable potentially to modulate the
      influence of NO on oxygen regimen. Myoglobin not only contributes to tissue O2
      supply, but it can locally affect the NO concentration. Acting as an NO scavenger
      under normoxia and as an NO producer under hypoxia, myoglobin together with NO
      can provide fine adjustment of muscle oxygen regimen via an increase in tissue
      pO, and elimination a mismatch between oxygen supply and demand.

PMID- 21870522
TI  - My first 20 years in neuroscience.
AB  - Intriguing facts were obtained in the first electrophysiological investigations
      (1964) that the action potentials (AP) produced by direct depolarization of the
      cell membrane in different species of mollusks showed specific relations to
      changes in external ionic composition. In Helix neurons, the generation of AP was
      well maintained in sodium-free solutions with high calcium or barium content. The
      amplitude of the spike overshoot in the case was linearly related to the
      logarithm of calcium concentration. It is interesting that increase in external
      calcium ions decreased the ionic conductance of the resting membrane (R0) also in
      linear relation to the logarithm of Ca2+ or Ba2+ concentration. It was found for
      the first time (1965) that addition of Ba2+ to the external solution produced in
      the neurons well-developed prolonged (protracted) APs in all cases. However, the
      excitability of Planorbis and Limnea neurons was rapidly (during 3 min)
      reversibly depressed in sodium-free solutions. We found that, after injections of
      horse radish peroxidase (HRP) in the spinal cord of cats, the enzyme was
      transported retrogradely to brain stem neurons in the bulbar medial reticular
      formation, the vestibular complex, and the red nucleus. We obtained (1975)
      intriguing facts in our investigations: we recorded the labeled neurons in the
      locus coeruleus and subcoeruleus, as well as in the paraventricular hypothalamic
      nucleus. The existence of straight pathways from hypothalamus to the spinal cord
      has not been demonstrated earlier. The next step of our study was to determine
      the corresponding spinal funiculi where descending fibers (from various brain
      stem cell groups) are located. Indeed, in our pioneer studies (1977), we found
      that the fibers from the hypothalamus, which descend throughout the spinal cord,
      are located mainly in the lateral funiculus, ipsilaterally.

PMID- 21870523
TI  - [Recognizing and making use of potential].

PMID- 21870524
TI  - [Comprehending and controlling risk factors].

PMID- 21870525
TI  - [An open window to the world].

PMID- 21870526
TI  - ["Nurses should be able to comfort..."].

PMID- 21870527
TI  - [Providing structured support for everyday life].

PMID- 21870528
TI  - [Pain therapy is team work].

PMID- 21870529
TI  - [New perspectives, new leadership, new culture].

PMID- 21870530
TI  - [The rollercoaster of emotions].

PMID- 21870531
TI  - [With doctors at eye level (interview by Urs Luthi)].

PMID- 21870532
TI  - [Health, choice or fate?].

PMID- 21870533
TI  - [A major event, the consequences underestimated].

PMID- 21870534
TI  - [Professional association: the future in perspective].

PMID- 21870535
TI  - [Experience of partnership].

PMID- 21870536
TI  - [The private market is growing].

PMID- 21870537
TI  - [Not everyone knows how to write "terrace"].

PMID- 21870538
TI  - [Tensions that lead to dismissal].

PMID- 21870539
TI  - [We are what we eat].

PMID- 21870540
TI  - [A new road map for eradication of HIV].

PMID- 21870541
TI  - [Tooth abscess: management in the field].
AB  - Tooth abscess can be diagnosed based solely on clinical findings. No additional
      studies are required. Abscess can be treated using a few basic instruments.

PMID- 21870542
TI  - [Hemoglobinopathy. Laboratory diagnosis].
AB  - Hemoglobinopathies are the most common genetic diseases in the world. They are
      most frequent in areas where malaria is endemic. Sickle cell disease and severe
      thalassemia require prompt diagnosis. The purpose of this article is to describe
      first-line techniques for diagnosis in non-specialized laboratories with special
      emphasis on the pitfalls of interpreting results.

PMID- 21870543
TI  - [Sanitary situation of the Senegal River Basin in 2010. Part II: vector-borne
      diseases and zoonoses].
AB  - In recent decades, the Senegal River Basin has witnessed an increase in the
      prevalence of water-borne human and animal diseases. The "Organization for the
      Development of the Senegal River" (French acronym, OMVS) decided to establish a
      "Water Resource Development and Management Framework Project" (French acronym,
      SDAGE) for the Senegal River Basin. The purpose of SDAGE is to avoid overuse of
      natural resources while allowing development of human activities in the Senegal
      River Basin. This project document is intended to provide guidance for mobilizing
      resources and understanding impact on the environment and local population
      through to 2025. Within the framework of the first phase of the SDAGE, a survey
      to assess water-borne diseases in the Senegal River Basin was carried out in
      2009. This assessment of the medical situation was based on documents obtained by
      bibliographic research. The purpose of this report is to summarize the main
      findings with regard firstly to vector-borne diseases along with corresponding
      national or regional control programs in the area and, secondly to zoonoses.
      Findings with regard to diseases directly related to water have been described in
      another report.

PMID- 21870544
TI  - [Analysis of the implementation of the Paris Declaration in the health sector in
      the Democratic Republic of Congo].
AB  - The authors analyze and present the position of stakeholders in the
      implementation of the Paris Declaration in the Democratic Republic of Congo. Five
      years after this Declaration concerning official development assistance (ODA),
      results are still uncertain and the road ahead remains long. Paradoxically
      resources provided through bilateral and multilateral cooperation have
      contributed to weakening the local health system. Principles such as alignment,
      harmonization and ownership are still rudimentary. Multiplication of project
      management frameworks and cutbacks in government healthcare spending have
      hindered efforts to rationalize healthcare sector funding. The effectiveness of
      ODA in the health sector is based mainly on pragmatic involvement on the part of
      regulatory officials and true commitment to the principles of the Paris
      Declaration on the part of donors. Efforts in this regard including the strategy
      to strengthen the health system and reform of health sector financing cannot
      succeed without improving governance at all levels.

PMID- 21870545
TI  - [XIIth medical days at Principal Hospital in Dakar (HPD): vascular disease in
      Senegal].

PMID- 21870546
TI  - [Albert Calmette (1863-1933). Description of the BCG vaccine inventor's stay in
      Gabon].
AB  - The purpose of this article is to describe Albert Calmette's stay in Gabon from
      October 1886 to November 1887. During his year in Africa, this illustrious French
      navy physician who was to invent the BCG vaccine against tuberculosis was keenly
      interested in malaria and sleeping sickness.

PMID- 21870547
TI  - [Echocardiography for extracardiac compression due to tuberculosis].

PMID- 21870548
TI  - [Nontraumatic digestive surgical emergencies in elderly patients at the Cocody
      University Hospital Center in Abidjan, Cote d'Ivoire: etiology and outcome].
AB  - OBJECTIVES: The purpose of this retrospective report is to describe etiologies
      and therapeutic outcomes of nontraumatic abdominal surgical emergencies in
      elderly patients. MATERIAL AND METHODS: The charts of patients aged 60 years or
      more who underwent emergency surgery for nontraumatic abdominal disorders at a
      Teaching Hospital in Abidjan, Cote d'Ivoire from August 1998 to July 2008 were
      reviewed. Demographic data, clinical findings, operative protocols, and
      postoperative outcomes were noted. RESULTS: A total of 137 patients with a mean
      age of 68.3 years (range, 60-93 years) underwent emergency surgery for
      nontraumatic abdominal disorders during the study period. The underlying
      etiologies were strangulated hernia (n = 40), abdominal parietal abscess (n = 6),
      bowel obstruction (n = 32), acute diffuse peritonitis (n = 29), acute
      appendicitis (n = 23), acute cholecystitis (n = 6) and massive rectorragy from
      colonic diverticulitis (n = 1). Coexisting medical problems (n = 84) were noted
      in 69 patients. Surgical procedures were tailored to operative findings. Twenty
      seven patients were admitted to the intensive care unit in the immediate
      postoperative period. Mean hospital stay was 7.7 days (range, 2-23 days).
      Surgical complications included wound infection (n = 14), stoma-related
      complications (n = 7), digestive fistula (n = 4), scrotal hematoma (n = 5) and
      postoperative evisceration (n = 2). The mortality rate was 10.21% (n = 14) mainly
      due to postoperative peritonitis. CONCLUSION: The findings of this study
      indicated that most nontraumatic abdominal surgical emergencies in elderly
      patients were related to complications of neglected or undiagnosed preexisting
      disease. Prognosis was related to the stage of the disorder, initial surgical
      management, and deterioration of the coexisting medical problems.

PMID- 21870549
TI  - [Predictive value of positive and negative results of the Widal and Felix test
      for typhoid fever in general practice in Niamey].
AB  - INTRODUCTION: Typhoid is a common reason for seeking medical care in general
      practice in the developing countries, Use of the Widal and Felix test is frequent
      in this setting. The purpose of this study carried out in private general
      medicine clinics in Niamey, Niger was to determine the incidence of typhoid and
      the predictive value of positive and negative results of the Widal test. MATERIAL
      AND METHOD: We used low published values of sensitivity (67.9%) and specificity
      (93.8%). Estimation of the incidence of typhoid was based on reports made to the
      national health information system of Niger by 3 private clinics in Niamey.
      RESULT: A total of 1725 persons attended the clinics between 1/12/07 and
      31/01/08, including 311 presenting nonspecific signs suggesting typhoid, i.e., at
      least fever and headache, and 172 presenting typhoid. The incidence was 9.97% in
      attendees overall and 55.31% in attendees with nonspecific evocative signs. The
      positive predictive value of the Widal and Felix test was 53.81% and the negative
      predictive value was 96.35% in attendees overall and 93.13% and 70.25%
      respectively in patients with clinical signs. CONCLUSION: Other diagnostic
      modalities such as PCR, coproculture, and hemoculture can be proposed, but are
      not available in this setting. The positive predictive value of the Widal test
      among patients with nonspecific signs suggesting typhoid is high. While not
      negligible, the negative predictive value in this high-incidence group is
      relatively low and should indicate monitoring.

PMID- 21870550
TI  - [Impact of armed conflict on the health care system of a sanitary district in
      Cote d'Ivoire].
AB  - Since September 2002, Cote d'Ivoire has been in the throes of armed conflict that
      has split the country in two. In the government-controlled area, access to health
      care services has continued. In the area under the control of the "New Forces",
      access to health care services decreased dramatically due to departure of
      qualified health personnel and subsequent shutdown of sanitary facilities. The
      purpose of this transversal descriptive survey was to measure the impact of this
      crisis on the health care system in the Seguela sanitary district that is located
      in the war zone. Findings showed that 60.7% of sanitary facilities are no longer
      operational, that 77.7% of qualified personnel have left their workstation, and
      that 46.2% of sanitary structures have been damaged. A few reference hospitals
      and sanitary facilitates have been able to remain open thanks to the support of
      the humanitarian organisations. As a result of declining access to health care
      services, a recrudescence of measles and IST has been observed and gastritis and
      traumatology have appeared among the top 10 causes of morbidity. Access to
      effective health care in the Seguela sanitary district cannot be envisioned
      without the return of qualified health care personnel and the renovation of the
      sanitary facilities.

PMID- 21870551
TI  - [Clinical and radiological features of tuberculosis during HIV infection in
      Libreville, Gabon].
AB  - OBJECTIVE: The purpose of this report is to describe the clinical and
      radiological features of tuberculosis during HIV infection. MATERIALS AND
      METHODS: This retrospective comparative study was based on review of patients
      treated between 2006 and 2010 in the Department of Medicine of the Military
      Hospital in Libreville, Gabon. A total of 156 patients with all types of
      tuberculosis were included, i.e., a study group of 78 tuberculosis patients co
      infected with HIV and a control group of 78 seronegative tuberculosis patients.
      Analysis was carried out on demographic, clinical and radiological data. RESULTS.
      Most patients in both groups were male. Mean patient age was 37.1 +/- 10.3 in the
      seropositive group and 29.5 +/- 11.5 in the seronegative group. Deterioration in
      general health was quantitatively higher in the seropositive group. Tuberculosis
      was confined to the lungs in 41% of patients co-infected with HIV and 55% of
      seronegative patients. Chest x-rays showed more extensive cavitation in
      seronegative patients. Mixed pulmonary and extrapulmonary disease was observed in
      20.5% of seropositive patients and 10.3% of seronegative patients. The CD4
      lymphocyte rate was not statistically different between patients with pulmonary
      versus extrapulmonary tuberculosis. CONCLUSION. Tuberculosis during HIV infection
      often has an atypical or banal clinical presentation. Radiological findings may
      be non-distinctive or even normal. For this reason, diagnosis of tuberculosis may
      be difficult.

PMID- 21870552
TI  - [Epidemiological features of intestinal parasitic infection in Burkina Faso from
      1997 to 2007].
AB  - A retrospective review of parasitic intestinal infections reported to the
      Ministry of Health of Burkina Faso from 1997 to 2007 was conducted. Study focused
      on the results of 904,733 stool examinations performed for parasite detection in
      public hospital parasitology laboratories. The overall positivity rate for
      intestinal parasite infection was 54.7%. Protozoa and helminths were identified
      in 32.0% and 8.0% of stool examinations respectively. The main parasites checked
      for were amoebas (29.8%), hookworms (5.7%), tapeworms (1.7%) and Schistosoma
      mansoni (1.6%). Parasites were detected throughout the country and the proportion
      of positive samples differed significantly from one region to another. These
      findings highlight the high frequency of laboratory diagnosis of intestinal
      parasitic infection and demonstrate the need to improve environmental sanitation
      and provide health education to the population.

PMID- 21870553
TI  - [Prevalence and parasite load of urinary schistosomiasis in schoolchildren in the
      Wilaya of Gorgol in Mauritania].
AB  - The purpose of this article is to describe the findings of a study carried out in
      a cohort of 610 schoolchildren aged 6-15 years to determine the prevalence of
      urinary schistosomiasis in Wilaya of Gorgol. The schistosomiasis prevalence rate
      was high ranging from 1.3 to 30.1% depending on location and from 7.9 to 13.7%
      according to age. Parasite loads up to 14 eggs/10 mL were measured. Children
      living in the wet zone were significantly more infected than those living in the
      intermediate and dry zones (p = 0.005). However, no significant difference in
      prevalence was found according to age (p = 0.258). Infection rate and parasite
      burden were correlated with exposure in terms of frequency of contact with
      permanent water sources. Schoolchildren in frequent contact with breeding grounds
      were more vulnerable to urinary schistosomiasis. Areas along the riverbank were
      more affected than areas located away from the river or permanent water sources.

PMID- 21870554
TI  - [Computerized temperature monitoring of the vaccine cold chain in a tropical
      climate, Chad].
AB  - Because new EPI liquid vaccines are highly sensitive to freezing and overheating,
      close monitoring of the cold chain is mandatory. The new Testostore 171-1
      electronic thermometer (Testo) provides more reliable monitoring of cold chain
      temperature than freezer indicators, vaccine vial monitors and color strips that
      only indicate if vaccines are out-of-date. The Testo thermometer uses a probe
      placed in refrigeration units to periodically measure and store temperature
      readings. Temperature curves are displayed via a USB connection on a laptop
      computer running special software (Comfort software light). Testo temperature
      data can easily be communicated to all management levels by e-mail. The first
      experience using the Testo system in Africa involved regional EPI supervision in
      Mondou, Logone Occidental, Chad. After a preliminary mission in Chad in 2006
      showed the feasibility of using this method to manage the national cold chain at
      all levels, a nurse was appointed as EPI supervisor and given a refresher course
      in Chad's capital Ndjamena in March 2009. In April-May 2009, the supervisor was
      sent back to the Logone Occidental Region to monitor, by himself, refrigeration
      units making up the regional and district cold chain for vaccine storage in five
      health centers (rural and urban). Temperature curve readings were performed on
      site in the presence of the medical staff and results were compared to those
      recorded twice a day on conventional temperature charts using lamellar
      thermometers installed in refrigerators doors. Testo curves showed that liquid
      vaccine storage temperatures fell below freezing too frequently and that
      temperatures readings of door thermometers were often inaccurate. Testo readings
      also detected power outages in refrigeration units used in urban settings and
      flame extinctions in kerosene lamp refrigerators due to refrigerator breakdown or
      windy weather conditions before the rainy season. The main advantage of this
      monitoring method is to provide reliable data as a basis not only for detection
      of possible freezing of liquid vaccines but also for discussion of cold chain
      management and improvement with medical staff.

PMID- 21870555
TI  - [Epidemiology of snakebites in Morocco].
AB  - This study was based on a retrospective descriptive analysis of all cases of
      snakebite recorded at the Poison Control and Pharmacovigilance Center of Morocco
      from 1980 to 2008. A total of 1,761 snakebites, i.e., 61 cases per year, were
      observed during the study period. Males accounted for 54.5% of victims (sex ratio
      (M/F) = 1.2) and 70% of cases occurred in rural areas. The average age of
      snakebite victims was 26.7 +/- 17.5 years. A seasonal snakebite peak was observed
      between May and August coinciding with the warmest period of the year, harvest
      time and snake migration. Sixty-two percent of patients presented clinical
      symptoms including respiratory, cardiovascular, gastrointestinal, neurological
      and mucocutaneous signs. The average fatality rate was 7.2% per year and the
      sequel rate was up to 1.04%. This study demonstrates that management of snakebite
      is problematic in Morocco. Morbidity was probably underestimated. Restricted
      access to antivenom is a major problem in rural areas where the population cannot
      afford the cost.

PMID- 21870556
TI  - [Prevalence of halitosis in patients with dental prostheses in Senegal].
AB  - INTRODUCTION: Bad breath is a disease affecting 25% of the world's population.
      Despite the widespread nature of this problem, people's knowledge about this
      condition is poor. OBJECTIVE: The purpose of this study was to determine the
      prevalence of halitosis in a cohort of 62 Senegalese subjects with dental
      prostheses. METHODS: Breath analysis was based on measurement of volatile sulfur
      compounds (VSC) using a halimeter. Halitosis was diagnosed ifVSC level was > or =
      125 ppb. RESULTS: Mean VSC level was 157.7 +/- 152.6 ppb. The prevalence of
      halitosis was of 35.4% overall, 72.7% in persons with fixed dentures and of 27.3%
      in persons with removable prostheses. CONCLUSION: The relatively high prevalence
      of halitosis observed in this study indicates a need to enhance patient awareness
      of daily hygiene measures for dental prosthesis.

PMID- 21870557
TI  - [Syphilis: 57 observations in Fez, Morocco].
AB  - A prospective study of syphilis cases over a period of 2 years (January 2008 to
      September 2009) was carried out in the Department of Dermatology of the Hassan II
      University Hospital Center in Fes, Morocco. A total of 57 cases were identified.
      The M/F sex ratio was 0.89. Mean patient age was 40.5 years (range, 22-80). Risk
      factors included unprotected sex in 96.5% of cases and multiple partners in
      42.1%. Nine patients had a history of sexually transmitted infection. No patient
      had received blood transfusion. Clinical picture was late latent syphilis in
      70.2% of cases (n = 41). Only one case was associated with human immunodeficiency
      virus. The mainstay treatment was intramuscular benzathine benzylpenicillin.
      Outcome was favorable in 48 cases.

PMID- 21870558
TI  - [Unassisted natural childbirth at the Talangai Central Hospital in Brazzaville,
      Congo].
AB  - OBJECTIVES: The purpose of this study was to determine the profile of women who
      give unassisted natural home childbirth (UNHC) in Brazzaville and to evaluate
      maternal and perinatal morbidity and mortality. PATIENTS AND METHODS: This
      prospective descriptive study was carried out at the Maternity Clinic of the
      Talangai Central Hospital (TCH) from November 1, 2006 to October 31, 2008.
      PATIENT SELECTION: Women who gave UNHC and were afterwards admitted to the TCH.
      RESULTS: The frequency of UNHC was 3.7%. The 19- to 35-year age bracket accounted
      for 72.6% of cases. The main causes underlying UNHC were ignorance of the initial
      clinical signs of labor for 37 of the 61 primipares (60.7%) and waiting for onset
      of labor before going to the hospital for 167 of the 360 paucipares and
      multipares (46.4%). For 234 women, UNHC occurred after pregnancy without prenatal
      care. In 57.8% of these cases, the reason for admission after UNCR was
      hemorrhage. More than half of the women (56.8%) who gave UNHC lived women live
      near a medical facility. Term pregnancies accounted for 41.3% cases of UNHC and
      undetermined term for 34.4%. At least one maternal complication was observed in
      65.3% of cases. Neonatal morbidity was observed in 24% of cases and perinatal
      mortality in 11.4%. CONCLUSION: UNHC is still common in Brazzaville owing mainly
      to poor public awareness. Public information campaigns to educate women to
      recognize the initial signs of labor could decrease the frequency of UNHC.

PMID- 21870559
TI  - [Impact of water quality and environmental sanitation on the health of
      schoolchildren in a suburban area of Benin: findings in the Savalou-Bante and
      Dassa-Glazoue sanitary districts].
AB  - OBJECTIVE: Promotion of environmental hygiene and sanitation in school districts
      contributes to community health. The purpose of the present study using
      physicochemical and biological parameters was to show the impact of these hygiene
      and sanitation measures on the health of schoolchildren in Collines Departement
      of Benin. MATERIALS AND METHODS: This prospective study was carried out in three
      selected primary schools from 28 September to 30 December 2007. A group of 210
      children (100 boys and 110 girls) was obtained by careful identification of
      schoolchildren who benefited from the program and simple random selection.
      Physicochemical and bacteriologic analysis of water distributed in schools,
      assessment of the clinical condition of schoolchildren and screening of their
      hands for pathogenic bacteria allowed us to evaluate the level of hygiene in
      schools. Existing sanitary equipment was evaluated by on-site visual inspection.
      RESULTS: Hand screening identified the presence of pathogenic microorganisms on
      the hands of 74% of schoolchildren. Diarrhea was observed in 30% of pupils,
      osteomyelitis in 15% and tooth dystrophy in 25%. Water quality analysis showed
      fluorine and nitrate concentrations of 3.5 mg/L and 15 mg/L respectively and
      demonstrated contamination by fecal bacteria, especially during storage.
      CONCLUSION: The present study revealed a high level of pathogenic organisms on
      hands and confirmed their presence in water. Training teaching staff about
      educating and monitoring pupils regarding sanitary standards and protocols is
      needed to improve the level of competency and of compliance with hygiene
      measures.

PMID- 21870560
TI  - [Endoscopic features of esophageal cancer in Dakar, Senegal: study of 76
      observations].
AB  - OBJECTIVE: In response to the lack of cancer register and paucity of publications
      on esophageal cancer in Senegal, this retrospective descriptive single-center
      study was undertaken to determine epidemiological, clinical, endoscopic and
      histological features of the disease at a digestive endoscopy center in Dakar.
      PATIENTS AND METHOD: Reports describing upper digestive tract endoscopy
      procedures performed at the Aristide Le Dantec Teaching Hospital in Dakar between
      January 2006 and December 2009 were reviewed. Cases involving histologically
      confirmed esophageal cancer were compiled and patient data including age, sex,
      and indication for endoscopy as well as endoscopic and histological findings were
      analyzed. RESULTS: A total of 78 reports were collected including 76 patients
      with suitable data for analysis. Esophageal cancer accounted for 0.97% of upper
      digestive tract endoscopy procedures performed. Mean patient age was 49 years and
      the sex-ratio was 1.9. The main indication for endoscopy was dysphagia (92.1%).
      The most frequent endoscopic finding involved budding lesions with (42%) or
      without (29%) ulceration. The most common location was the middle third of the
      esophagus (50%). The most frequent histological type was squamous cell carcinoma
      (92.1%). CONCLUSION: Esophageal cancer observed at the endoscopy center of the
      Aristide Le Dantec Teaching Hospital in Dakar mainly affects young male adults.
      Lesions are generally located in the middle third of the esophagus and
      corresponded to squamous cell cancer. There is a need to establish a cancer
      register and to conduct multicentric studies to gain insight into risk factors
      for esophageal cancer in Senegal.

PMID- 21870561
TI  - [First case of presumed sporadic Creutzfeldt-Jakob Disease in Marrakech,
      Morocco].
AB  - INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (CJD) is the most common form of
      subacute spongiform encephalopathy. The first case of sporadic CJD in Morocco was
      confirmed by postmortem histology in 2005. The absence of laboratory facilities
      for diagnosis of prion disease has resulting in underestimation of the incidence
      of CJD in Morocco. The purpose of this report is to describe another case of
      sporadic CJD. The patient was a 61-year-old farmer. Medical history included
      diabetic diet and poorly monitored but the patient had never received hormone
      therapy or undergone surgery or blood transfusion. There were no similar cases in
      the patient's family or entourage. Diagnosis of presumed sporadic CJD was based
      on absence of similar family cases and surgical history and on presence of
      rapidly progressive dementia, myoclonus, visual troubles, extrapyramidal
      syndrome, akinetic mutism and typical EEG. Brain magnetic resonance imaging (MRI)
      depicted supratentorial demyelination. The 14.3.3 protein was detected in
      cerebrospinal fluid (CSF). Other biological tests were normal. Supportive care
      included administration of a antihypertensive drug and nursing. The patient died
      four months after the onset of symptoms. CONCLUSION: Occurrence of CJD in Morocco
      is probably underestimated and the authors underline the need to set up
      specialized laboratory facilities for diagnosis of transmissible spongiform
      encephalopathy.

PMID- 21870562
TI  - [Hemolytic anemia after voluntary ingestion of henna (Lawsonia inermis) decoction
      by a young girl with G6PD deficiency].
AB  - Henna (Lawsonia inermis) is a shrub bearing leaves that are crushed and used for
      cosmetic purposes in Asia and Africa. In several countries, henna decoction is
      ingested as a traditional drug to induce abortion. One component of Henna, known
      as Lawsone, can induce hemolysis in G6PD-deficient patients after cutaneous
      exposure or ingestion. The purpose of this report is to describe a case of severe
      hemolytic anemia after voluntary ingestion of Henna decoction to induce abortion.
      This complication led to diagnosis of partial moderate G6PD-deficiency in the 17
      year-old patient living in Mayotte in the Indian Ocean. This report emphasizes
      the life-threatening hazards associated with some plant extracts used as
      traditional medicines.

PMID- 21870563
TI  - [Pericardial effusion with pretamponade leading to diagnosis of hypothyroidism:
      two cases in Congo].
AB  - The purpose of this report is to describe two cases of pericardial effusion with
      pre-tamponade leading to diagnosis of underlying hypothyroidism. Both patients
      were women with large longstanding pericardial effusion. The first patient was 47
      years-old and the second was 46. Diagnosis of hypothyroidism, whose clinical
      features were equivocal in the first case case and frank in the second, was
      confirmed by hormone tests. Treatment consisted of pericardial drainage and
      hormone replacement therapy with increasing doses. Outcome was favorable in both
      cases with restoration of euthyroidism. Clinical status was satisfactory in both
      cases with a follow-up of five months in the first patient and three months in
      the second. Pericardial effusion with pretamponade is an exceptional complication
      of prolonged hypothyroidism that should be considered in patients presenting with
      large longstanding but well tolerated pericardial effusion with no evidence of
      infection or inflammation.

PMID- 21870564
TI  - [Resistance of Plasmodium falciparum to antimalarial drugs: impact on malaria pre
      elimination in Madagascar].
AB  - The purpose of this review was to provide up-to-date information on the
      resistance of Plasmodium falciparum to the main antimalarials used in Madagascar
      and to assist implementation of the malaria control and elimination program. In
      2006, the failure rate for chloroquine treatment was 44% (n = 300) and was
      comparable to the rate observed in continental Africa. Most treatment failures
      occurred after the first week of follow-up. P. falciparum resistance to
      chloroquine appeared to be special in Madagascar with only 3.2% of isolates
      showing in vitro resistance (n = 372, 7 sentinel sites) and less than 1%
      harbouring mutant parasites within the Pfcrt gene. Conversely, the Pfmdr1 N86Y
      point mutation was found in 64.3% (n = 174) of isolates in 2006 and in 51.7% (n =
      343) in 2007. Failure of combined sulfadoxine-pyrimethamine therapy, i.e., the
      recommended intermittent preventive treatment for malaria during pregnancy, and
      in vitro resistance to pyrimethamine were rare. However, the Pfdhfr 51I/59R/108N
      allele showed consistently high prevalence levels reaching 33.3% in 2008.
      Moreover, the single Pfdhfr 164L mutant allele, a haplotype unique to Madagascar,
      was discovered in 2006 and showed prevalence rates up to 30% in some locations
      (southeast) in 2008. Up to now, the quadruple mutant allele Pfdhfr
      51I/59R/108N/164L has not been observed. Susceptibility to the other
      antimalarials tested appeared excellent but the number of isolates showing in
      vitro susceptibility to artemisinin derivatives has been fallen in recent years
      and this decline may herald a decrease in the efficacy of these drugs.

PMID- 21870565
TI  - [A case of curable encephalomyelitis in a tropical area: pernicious anemia].
AB  - Pernicious anemia is uncommon in Africa. The purpose of this report is to
      describe a case of pernicious anemia observed in Madagascar. The revealing
      manifestation was encephalomyelitis with combined medullar sclerosis that
      responded favorably to vitamin B12 replacement therapy. Clinical symptoms
      included paresthesia associated with allodynia of all four extremities and with
      tetrapyramidal syndrome, medullar ataxia and minor cognitive disturbances ongoing
      for 5 months. Hemogram testing revealed macrocytic anemia. Serum cobalamin level
      was low. Anti-intrinsic factor antibody was detected. Spinal cord magnetic
      resonance imaging showed diffuse high-signal intensity along the posterior spinal
      cord extending from C1 to C4. Vitamin B12 replacement therapy led to full
      regression of clinical signs after six weeks. Association of central nervous
      system involvement with macrocytic anemia suggests vitamin B12 deficiency and
      pernicious anemia should be suspected. This disease can be considered as a
      curable form of myelitis in Africa and Madagascar.

PMID- 21870566
TI  - [Central precocious puberty due to hypothalamic hamartoma in Cameroon].
AB  - Hypothalamic hamartoma is an uncommon cause of central precocious puberty and
      sometimes of gelastic epilepsy and delayed development. The purpose of this
      report is to describe a case of central precocious puberty in an 18-month-old
      girl who was referred to our department for further investigation of vaginal
      bleeding that had appeared during the 8th month of life. The patient's puberty
      was compatible with Tanner stage 3, her psychomotor development was normal, and
      epilepsy was not observed. Diagnosis was based on abnormal hormonal workup
      findings and discovery of a hypothalamic hamartoma on brain magnetic resonance
      imaging. Neurosurgery was not performed. Administration of long-acting
      gonadotropin releasing hormone analog to slow puberty led to clinical
      improvement. Hypothalamic hamartoma must always be suspected in case of central
      precocious puberty. Although magnetic resonance imaging is the most reliable
      modality, it is not always available nor affordable in low-income countries.
      Neurosurgery is not indicated in patients without epileptic seizure. Gonadotropin
      releasing hormone agonists are usually indicated to slow down puberty and improve
      the adult height. However, the cost is prohibitive in developing countries.

PMID- 21870567
TI  - [Trends in incidence of cutaneous leishmaniasis from 1999 to 2005 in Ouagadougou,
      Burkina].
AB  - The purpose of this study is to describe trends in the annual incidence of
      cutaneous leishmaniasis in Ouagadougou, Burkina from 1999 to 2005. Data recorded
      at city health care centers were reviewed. A total of 7,444 cases of cutaneous
      leishmaniasis were observed, with an annual mean incidence of 1,063.3 +/- 270.8
      cases. The M/F sex ratio was 0.9. Mean patient age was 22.8 +/- 13.5 years.
      Patients older than 15 years accounted for 72.5% of the population. The
      predominant age bracket was 16-30 years (51.80%).A decrease in incidence was
      observed from March to June and in December. Peak incidence occurred in September
      and October. Over the 7-year study period, the average incidence rate was 0.1% +/
      0.04. Since this rate does not reflect the real prevalence of the disease, a
      prospective study is needed.

PMID- 21870568
TI  - [Practice design supports the vision of the entrepreneur].

PMID- 21870569
TI  - [Frustration with a pup in shock condition].

PMID- 21870570
TI  - [Looking beyond just making the animals better].

PMID- 21870571
TI  - [KNMVD 150 years: together in the spotlight].

PMID- 21870572
TI  - [Surveillance].

PMID- 21870573
TI  - [The presence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in
      companion animals in the Netherlands].
AB  - The presence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in
      companion animals in The Netherlands. This article reports about a research that
      is done to determine the presence of Capnocytophaga canimorsus and Capnocytophaga
      cynodegmi in companion animals in the Netherlands using a species specific PCR in
      combination with classic microbial isolation. Because of the high presence of the
      bacteria in the mouth of especially cats and dogs (respectively 21 and 19%) and
      the severe consequences of an infection for humans the risk of an infection with
      C. canimorsus is high. Therefore owners of cats and dogs should be informed about
      this risk especially if the owners belong to specific risk groups like elderly
      people, pregnant women, young children and immune deficient patients.

PMID- 21870574
TI  - [Antibiotics: from the way it works to antibacterial therapy part I (of IV)].

PMID- 21870576
TI  - [Concept transmission Eimeria is of importance in control of coccidiosis in
      chicks].

PMID- 21870575
TI  - [Pilot study: serological research of Bovine Respiratory Syncytial Virus and
      Mannheimia haemolytica in young cattle at dairy farms in the Netherlands].

PMID- 21870577
TI  - [Food supply security through intensive and sustainable agriculture].

PMID- 21870578
TI  - [The "tick busters" survey].

PMID- 21870579
TI  - [Know what you will get later].

PMID- 21870580
TI  - [Animals help forget the busy hospital].

PMID- 21870581
TI  - [Application of the Danish Herd Health Management in the Netherlands].

PMID- 21870582
TI  - [What a veterinarian should know about price elasticity].

PMID- 21870583
TI  - [West Nile Virus on the rise: alertness recommended].

PMID- 21870584
TI  - [Complementary working?].

PMID- 21870585
TI  - [Practice-Science-Order keeper: Jaap Aukema. Interviewed by Andries van Foreest
      and Ko Minderhoud].

PMID- 21870586
TI  - [TIme = Money].

PMID- 21870587
TI  - [Brooke Hospital for Animals for health of working animals for the most
      impoverished].

PMID- 21870588
TI  - A revival of the privacy protection of health-related personal information?

PMID- 21870589
TI  - Disclosure of medical data to relatives after the patient's death: recent legal
      developments with respect to relatives' entitlements in the Netherlands.
AB  - In the Netherlands the physician is still bound to professional confidentiality
      after the patient's death. However, in the legal doctrine and in case law some
      exceptions have been recognized, especially for circumstances where the relatives
      have a legitimate interest in the inspection of medical records of the deceased.
      Today developments as regards the Dutch proposal to new legislation on patients'
      rights, notably the proposed insertion of a provision stipulating the conditions
      under which the relatives have a right of access to medical records of the
      deceased, give cause for renewed consideration of this issue related to legal
      protection after death. This article explores whether the proposed provision
      corresponds to the prevailing principles regarding disclosure of medical data
      after death. It is concluded that there is a need to reconsider the provision's
      wording or to adhere to self-regulation of the Royal Dutch Medical Association in
      order to strike an appropriate balance between the various interests concerned.

PMID- 21870590
TI  - Use of the dead body in healthcare and medical training: mapping and balancing
      the legal rights and values.
AB  - By exploring the central legal principles and issues regarding usage of the dead
      body in healthcare and especially in medical training, this article aims at
      drawing some general conclusions on the legal status of the dead body and the
      protection of the deceased's integrity, dignity and autonomy. The article
      demonstrates that the use of the cadaveric body for scientific and educational
      purposes involves a redrawing of the traditional boundaries between the decent
      and the indecent, making these acts acceptable that would otherwise be regarded
      as assaults on the sanctity of bodily boundaries. This is made possible by the
      fact that the underlying principle of dignity is not perceived to be of an
      absolute nature when applicable to deceased persons.

PMID- 21870591
TI  - Saviour-sibling and the psychological, ethical and judicial issues that it
      creates: should English and French legislators close the Pandora's Box?
AB  - Since the advent of test-tube babies, advances in the biomedical field have risen
      steadily. In parallel, the scientific body has never since ceased to debate the
      ethical issues that they arise. This is particularly the case regarding saviour
      sibling. Saviour-sibling refers to a child who is conceived to cure an older
      brother or sister suffering from a serious family genetic disease. Therefore, it
      is meant to give birth to a child who will provide stem-cells taken from the
      umbilical cord or bone marrow afterwards, to treat an elder sick sibling. In
      England, this practice has been explicitly allowed by the new Human Fertilisation
      and Embryology Act 2008 under some strict conditions. In France, this practice,
      authorized by the Bioethics Law of August 2004 and confirmed by its decree of
      implementation published in the Official Journal on 23 December 2006, is also
      strictly regulated. This technique opens up new perspectives and enormous hope.
      Its legalisation is certainly justified by the suffering of the parents and to
      avoid that they travel to other States where it is permitted. However, it raises
      serious psychological ethical and judicial issues. Following an analysis of the
      English and French laws on saviour siblings, its controversial side will be
      highlighted, before concluding whether or not this new Pandora's box which is
      saviour-sibling, should be closed and other alternative methods encouraged.

PMID- 21870592
TI  - Access to advanced therapy medicinal products in the EU: where do we stand?
AB  - The European Union has a public health strategy and will generally ensure in all
      its policies and activities a "high level of human health protection". The new
      Regulation (EC) n 1394/2007 on advanced therapy medicinal products (ATMP), stems
      from this global policy and aims to harmonise access to the ATMP market. A real
      will for the harmonisation is clearly expressed in legal texts and enforced in
      the implementable procedures and requirements. However, several barriers remain.
      On the one hand, the scope of the ATMP Regulation is limited. On the other hand,
      Member States benefit from a wide margin of action.

PMID- 21870593
TI  - The medically examined applicant for private insurance and his/her right to
      informed consent: a comparative analysis.
AB  - Within the context of health and insurance law, an important question that arises
      is "to what extent is an applicant for private insurance truly capable of giving
      his/her 'free' and informed consent for a medical examination?". It should be
      borne in mind that it is the private insurer who requires a medical examination
      in order to gather medical information, and, moreover, that the insurer will not
      be inclined to conclude or carry out an insurance contract without this medical
      information. A distinction has to be made between not being free by legal
      coercion and not being (completely) free by factual circumstances. Exercising the
      right to informed consent involves exactly weighing up the consequences of the
      decision. Hence the applicant must be put in a position of being able to weigh up
      the consequences and take them into consideration.

PMID- 21870594
TI  - ECHR 2011/10 Case of Haas v. Switzerland, 20 January 2011, no. 31322/07 (First
      Section).

PMID- 21870595
TI  - ECHR 2011/11 Case of Kupczak v. Poland, 25 January 2011, no. 2627/09 (Fourth
      Section).

PMID- 21870596
TI  - ECHR 2011/12 Case of Kharin v. Russia, 3 February 2011, no. 37345/03 (First
      Section).

PMID- 21870597
TI  - ECHR 2011/13 Case of Dubetska and others v. Ukraine, 10 February 2011, no.
      30499/03 (Fifth Section).

PMID- 21870598
TI  - ECJ 2011/*, Commission v. France, 16 December 2010 (Case C-89/09).

PMID- 21870599
TI  - ECJ 2011/*, Commission v. Grand Duchy of Luxembourg, 27 January 2011 (Case C
      490/09).

PMID- 21870600
TI  - [Drug discovery and natural products: end of era or an endless frontier?].

PMID- 21870601
TI  - [Computer modeling of the promising inhibitors of the HIV-1 subtype A replication
      as a framework for the rational anti-aids drug design].
AB  - The model of the structural complex of cyclophilin B belonging to the
      immunophilins family with the HIV-1 subtype A V3 loop presenting the principal
      neutralizing determinant of the virus gp120 envelope protein as well as
      determinants of cell tropism and syncutium formation was generated by molecular
      docking methods. Basing on the conformational and energy characteristics of the
      built complex, computer-aided design of the polypeptide able to block effectively
      the functionally crucial V3 segments was implemented. From the joint analysis of
      the results derived with the data of literature, the generated molecule was
      suggested to offer a promising pharmacological substance for making a reality of
      the protein engineering projects aimed at developing the anti-AIDS drugs able to
      stop the HIV's spread.

PMID- 21870602
TI  - [Changes of doxorubicin distribution in blood and plasma after its inclusion into
      nanophospholipd formulation].
AB  - The drug composition based on the plant phospholipids and the antitumor drug
      doxorubicin (particle size <30 nm) was obtained using original technology
      elaborated in the Institute of Biomedical Chemistry (Russian Academy of Medical
      Sciences). In in vitro experiments demonstrated decreased drug association with
      blood cells for this nanophospholipid form as compared with free doxorubicin.
      This was accompanied by a with corresponding increase in its plasma level ans
      also by drug redistribution from plasma protein fraction to high density
      lipoproteins. Significance of these changes for doxorubicin biodistributon and
      antitumor activity is discussed.

PMID- 21870603
TI  - [Effects of organic selenium substance, selenomethionine, in acute alcohol
      intoxication].
AB  - The effect of the preliminary saturation of rats with selenomethionine (50 g/kg,
      intragastrically, daily, 10 days) prior to acute alcohol intoxication (5 g/kg,
      20% ethanol solution, intragastrically, singly on the 11th day with the exposure
      for 2 hours) was investigated. The activities of glutathione peroxidases
      (gastrointestinal mucosa, blood plasma, erythrocytes, liver), the levels of
      oxidized and reduced glutathione, LPO intensity and blood corticosterone level
      were studied.

PMID- 21870604
TI  - [Biochemical characteristics of iodperoxidase activity of human saliva].
AB  - Peroxidase-catalyzed oxidation of iodide in human saliva leads to the formation
      of a brown product with lambda max 287 nm and 353 nm (I3-) identified by the
      method of UV-spectrophotometry. I3- directly reacts with starch producing the
      characteristic blue complex. Salivary iodide peroxidase activity was found to be
      from 1.2 to 2.3 times higher then the activity of salivary peroxidases with
      natural substrates (SCN- and Cl-). Optimum for the iodide peroxidase activity in
      human saliva was found to be near pH 5.8. Salivary iodide peroxidase activity
      progressively lowers with the rise of pH value of the reaction mixture until
      total loss at the pH>7.4 was observed. Iodide peroxidase activity in human saliva
      at pH>7.4 is masked due to decomposition of I3- with the increase of pH along
      with the inhibition of peroxidases and I3- reduction by low molecular weight
      dialyzable salivary components possibly by Cl- and NCS-. Salivary iodide
      peroxidase activity was completely inhibited by peroxidase inhibitors (NaN3, 2
      mercaptoethanol, thiourea), while addition of the peroxidase alternative
      substrates (ascorbate, quercetin, thiocyanate) resulted in partial inhibition of
      iodide peroxidase activity. The results of the study confirm the idea, that high
      activity of human saliva peroxidase with iodide as a substrate may play a crucial
      role in the bioavailability and metabolism of biologically active iodide.

PMID- 21870605
TI  - [Accumulation of porphyrins in cells of system of blood induced by 5
      aminolaevulinic acid].
AB  - The levels and rates of accumulation of porphyrins in lymphoid cells and bone
      marrow cells treated with exogenous 5-aminolaevulinic acid (ALA) were studied.
      The dependence of the quantity of porphyrins accumulated in cell on ALA
      concentrations in the medium had maximum at 0.7-1.0 mM ALA for all the cell types
      studied (splenocytes, thymocytes, peripheral blood lymphocytes and bone marrow
      cells). The rate of accumulation of uro-, copro- and protoporphyrins depended on
      cell types. The lowest and the highest levels were found in splenocytes and
      highest in bone marrow cells respectively. It is suggested that photodynamic
      therapy employing ALA is potentially dangerous for blood cells.

PMID- 21870606
TI  - [Modification of collagen during action light].
AB  - In work chemical modification of collagen during action visible spectrum
      sunlight. These changes of collagen were found to indicate a photodegradation and
      photooxidation processes in collagen.

PMID- 21870607
TI  - [The influence of oxidized fibrinogen on apoptosis of endothelial cells].
AB  - Oxidative stress plays an important role in cardio-vascular diseases and
      atherosclerosis. Fibrinogen (FB), plasma coagulation protein, is a risk factor of
      atherosclerosis. Importantly, it can be readily oxidized during oxidative stress
      and in pathological conditions. FB can promote angiogenesis by supporting
      migration and proliferation of endothelial cells. On the other hand, recent
      reports demonstrated cytotoxicity of oxidized fibrinogen (oxFB). Endothelial
      dysfunction plays a critical role in the atherosclerosis development, therefore
      it is important to understand the effect of oxFB on human endothelial cells
      (hEC), and the mechanism of the cell death. Here, we studied influence of oxFB on
      hEC during 24 h incubation in two conditions: (1) at low serum level (0.1%) and
      in the absence of growth factors ("starvation"); (2) in full medium (5% FBS) with
      growth factor supplement. Apoptosis was evaluated using analysis of nuclear
      morphology, phosphatidylserine externalization on hEC surface and caspase-3
      activation. In starvation, we observed significant cell death via apoptosis. FB
      prevented starvation-induced cell death and caspase activation. Caspase activity
      in the presence of oxFB was 1.5 times higher as compared to FB, yet oxFB
      demonstrated significant cell protection during stress. Similarly, in optimal
      cultivation conditions FB decreased the rate of apoptosis by three times, while
      oxFB supported cell viability to the lesser extent. Thus, FB can protect hEC in
      stress conditions (in starvation); oxidative modification of FB diminishes its
      antiapoptotic properties.

PMID- 21870608
TI  - [Influence of alpha-lipoic acid on liver glutathione system of healthy and
      Ehrlich ascites carcinoma transplanted mice].
AB  - Influence of alpha-lipoic acid (LA) on liver glutathione system of Ehrlich
      ascites carcinoma (EAC) transplanted mice was studied. LA causes multidirectional
      influence on glutathione system of healthy mice. EAC transforms LA influence,
      strengthening prooxidative effects more expressed at introduction in early terms
      after inoculation of the tumor. The mechanism explaining realization of LA
      prooxidative effects as a result of interaction with glutathione system is
      suggested.

PMID- 21870609
TI  - [Glutathione-dependent enzymes and glucose-6-phosphate dehydrogenase of blood in
      patients with lymphosarcoma (non-Hodgkin's disease)].
AB  - Activities of glutathione-dependent enzymes and glucose-6-phosphate dehydrogenase
      (GPDH) were studied in blood of the patients with lymphosarcoma (LS). The
      activity of glutathione reductase (GR), glutathione dehydroascorbate reductase
      (GDAR), gamma-glutamyltranspeptidase (GGT) and G6PDH in plasma, leucocytes,
      lymphocytes and erythrocytes of peripheral blood in 30 patients (42-56 years)
      with LS and in 20 healthy have been determined with spectrophotometric methods
      (Humalyzer 2000 DE). Leucocytes and lymphocytes were separated from blood using
      Boyum method. Spearmen method used for correlative analysis. The levels of
      enzymes activity and results of correlative analysis showed an imbalance of
      antioxidative system defense and metabolic disturbances in patients with LS. The
      strong functional interrelation was estimated only between GR and G6PDH in the
      patients' lymphocytes (r=+0,716; p<0.0005). Interrelation was found between the
      levels of activity of antioxidative enzymes and activity (stage) of pathologic
      process, this may be used as the additional biochemical test for differential
      diagnostics of LS and estimation of the cells proliferative activity.

PMID- 21870610
TI  - [Sustained release of the antitumor drug paclitaxel from poly(3-hydroxybutyrate)
      based microspheres].
AB  - Development of systems of medicines with sustained action on the basis of
      biodegradable polymers is a promising trend in modem pharmacology.
      Polyhydroxyalkanoates (POA) attract increasing attention due to their
      biodegradability and high biocompatibility, which make them suitable for
      development of novel drug dosage forms. We obtained microspheres on the basis of
      poly(3-hydroxybutyrate) (PHB) loaded with the antitumor drug paclitaxel.
      Morphology, drug release kinetics and effect on tumor cells in vitro of
      microspheres were studied. The data on the kinetics of drug release,
      biocompatibility and biological activity of the biopolymer microspheres in vitro
      showed that the studied system of prolonged drug release had lower toxicity and
      higher efficiency compared to the traditional dosage forms of paclitaxel.

PMID- 21870611
TI  - Phylogenetically diverse grasslands are associated with pairwise interspecific
      processes that increase biomass.
AB  - Biodiversity is an important determinant of primary productivity in experimental
      ecosystems. We combine two streams of research on understanding the effects of
      biodiversity on ecosystem function: quantifying phylogenetic diversity as a
      predictor of biodiversity effects in species-rich systems and the contribution of
      pairwise interspecific interactions to ecosystem function. We developed a
      statistical model that partitions the effect of biodiversity into effects due to
      community phylogenetic diversity and other community properties (e.g., average
      pairwise interaction, between- and within-functional-group effects, and so
      forth). The model provides phylogenetically based species-level explanations of
      differences in ecosystem response for communities with differing species
      composition. In two well-known grassland experiments, the model approach provides
      a parsimonious description of the effects of diversity as being due to the joint
      effect of the average pairwise statistical interaction and to community
      phylogenetic diversity. Effects associated with functional groupings of species
      in communities are largely explained by community phylogenetic diversity. The
      model approach quantifies a direct link between a measure of the evolutionary
      diversity of species and their interactive contribution to ecosystem function. It
      proves a useful tool in developing a mechanistic understanding of variation in
      ecosystem function.

PMID- 21870612
TI  - Recovery of plant species richness during long-term fertilization of a species
      rich grassland.
AB  - Nutrient enrichment of habitats (eutrophication) is considered to be one of the
      main causes of plant diversity decline worldwide. Several experiments have shown
      a rapid loss of species in the first years after fertilization started. However,
      little is known about changes in species richness in the long term. Here, we use
      a 50-year-old field experiment with a range of fertilization treatments in
      grasslands that were mown twice each year in the center of The Netherlands. We
      show that species richness in all plots initially declined but started to recover
      after approximately 25 years of continued fertilization. This was also true for
      the heavily fertilized treatment (NPK). In NPK-fertilized plots, the decline was
      strongest and associated with a strong divergence of plant trait composition from
      the control, reflecting a shift to a plant community adapted to nutrient-rich
      conditions. During the subsequent period of increase in species richness, the
      trait composition remained stable. These results show that plant species richness
      can, at least partially, recover after an initial diversity decline caused by
      fertilization.

PMID- 21870613
TI  - Connell and Slatyer's models of succession in the biodiversity era.
AB  - Understanding how species interactions drive succession is a key issue in
      ecology. In this study we show the utility of combining the concepts and
      methodologies developed within the biodiversity-ecosystem functioning research
      program with J. H. Connell and R. O. Slatyer's classic framework to understand
      succession in assemblages where multiple interactions between early and late
      colonists may include both inhibitory and facilitative effects. We assessed the
      net effect of multiple species interactions on successional changes by
      manipulating the richness, composition, and abundance of early colonists in a low
      shore assemblage of algae and invertebrates of the northwestern Mediterranean.
      Results revealed how concomitant changes in species richness and abundance can
      strongly alter the net effect of inhibitory vs. facilitative interactions on
      succession. Increasing richness of early colonists inhibited succession, but only
      under high levels of initial abundance, probably reflecting the formation of a
      highly intricate matrix that prevented further colonization. In contrast,
      increasing initial abundance of early colonists tended to facilitate succession
      under low richness. Thus, changes in abundance of early colonists mediated the
      effects of richness on succession.

PMID- 21870614
TI  - Interacting trophic forcing and the population dynamics of herring.
AB  - Small pelagic fish occupy a central position in marine ecosystems worldwide,
      largely by determining the energy transfer from lower trophic levels to predators
      at the top of the food web, including humans. Population dynamics of small
      pelagic fish may therefore be regulated neither strictly bottom-up nor top-down,
      but rather through multiple external and internal drivers. While in many studies
      single drivers have been identified, potential synergies of multiple factors, as
      well as their relative importance in regulating population dynamics of small
      pelagic fish, is a largely unresolved issue. Using a statistical, age-structured
      modeling approach, we demonstrate the relative importance and influence of bottom
      up (e.g., climate, zooplankton availability) and top-down (i.e., fishing and
      predation) factors on the population dynamics of Bothnian Sea herring (Clupea
      harengus) throughout its life cycle. Our results indicate significant bottom-up
      effects of zooplankton and interspecific competition from sprat (Sprattus
      sprattus), particularly on younger age classes of herring. Although top-down
      forcing through fishing and predation by grey seals (Halichoerus grypus) and
      Atlantic cod (Gadus morhua) also was evident, these factors were less important
      than resource availability and interspecific competition. Understanding key
      ecological processes and interactions is fundamental to ecosystem-based
      management practices necessary to promote sustainable exploitation of small
      pelagic fish.

PMID- 21870615
TI  - Using the negative binomial distribution to model overdispersion in ecological
      count data.
AB  - A Poisson process is a commonly used starting point for modeling stochastic
      variation of ecological count data around a theoretical expectation. However,
      data typically show more variation than implied by the Poisson distribution. Such
      overdispersion is often accounted for by using models with different assumptions
      about how the variance changes with the expectation. The choice of these
      assumptions can naturally have apparent consequences for statistical inference.
      We propose a parameterization of the negative binomial distribution, where two
      overdispersion parameters are introduced to allow for various quadratic mean
      variance relationships, including the ones assumed in the most commonly used
      approaches. Using bird migration as an example, we present hypothetical scenarios
      on how overdispersion can arise due to sampling, flocking behavior or
      aggregation, environmental variability, or combinations of these factors. For all
      considered scenarios, mean-variance relationships can be appropriately described
      by the negative binomial distribution with two overdispersion parameters. To
      illustrate, we apply the model to empirical migration data with a high level of
      overdispersion, gaining clearly different model fits with different assumptions
      about mean-variance relationships. The proposed framework can be a useful
      approximation for modeling marginal distributions of independent count data in
      likelihood-based analyses.

PMID- 21870616
TI  - Improving occupancy estimation when two types of observational error occur: non
      detection and species misidentification.
AB  - Efforts to draw inferences about species occurrence frequently account for false
      negatives, the common situation when individuals of a species are not detected
      even when a site is occupied. However, recent studies suggest the need to also
      deal with false positives, which occur when species are misidentified so that a
      species is recorded as detected when a site is unoccupied. Bias in estimators of
      occupancy, colonization, and extinction can be severe when false positives occur.
      Accordingly, we propose models that simultaneously account for both types of
      error. Our approach can be used to improve estimates of occupancy for study
      designs where a subset of detections is of a type or method for which false
      positives can be assumed to not occur. We illustrate properties of the estimators
      with simulations and data for three species of frogs. We show that models that
      account for possible misidentification have greater support (lower AIC for two
      species) and can yield substantially different occupancy estimates than those
      that do not. When the potential for misidentification exists, researchers should
      consider analytical techniques that can account for this source of error, such as
      those presented here.

PMID- 21870617
TI  - Inference about density and temporary emigration in unmarked populations.
AB  - Few species are distributed uniformly in space, and populations of mobile
      organisms are rarely closed with respect to movement, yet many models of density
      rely upon these assumptions. We present a hierarchical model allowing inference
      about the density of unmarked populations subject to temporary emigration and
      imperfect detection. The model can be fit to data collected using a variety of
      standard survey methods such as repeated point counts in which removal sampling,
      double-observer sampling, or distance sampling is used during each count.
      Simulation studies demonstrated that parameter estimators are unbiased when
      temporary emigration is either "completely random" or is determined by the size
      and location of home ranges relative to survey points. We also applied the model
      to repeated removal sampling data collected on Chestnut-sided Warblers (Dendroica
      pensylvancia) in the White Mountain National Forest, U.S.A. The density estimate
      from our model, 1.09 birds/ha, was similar to an estimate of 1.11 birds/ha
      produced by an intensive spot-mapping effort. Our model is also applicable when
      processes other than temporary emigration affect the probability of being
      available for detection, such as in studies using cue counts. Functions to
      implement the model have been added to the R package unmarked.

PMID- 21870618
TI  - Spatial scale and species identity influence the indigenous-alien diversity
      relationship in springtails.
AB  - Although theory underlying the invasion paradox, or the change in the
      relationship between the richness of alien and indigenous species from negative
      to positive with increasing spatial scale, is well developed and much empirical
      work on the subject has been undertaken, most of the latter has concerned plants
      and to a lesser extent marine invertebrates. Here we therefore examine the extent
      to which the relationships between indigenous and alien species richness change
      from the local metacommunity to the interaction neighborhood scales, and the
      influences of abundance, species identity, and environmental favorability
      thereon, in springtails, a significant component of the soil fauna. Using a suite
      of modeling techniques, including generalized least squares and geographically
      weighted regressions to account for spatial autocorrelation or nonstationarity of
      the data, we show that the abundance and species richness of both indigenous and
      alien species at the metacommunity scale respond strongly to declining
      environmental favorability, represented here by altitude. Consequently, alien and
      indigenous diversity covary positively at this scale. By contrast, relationships
      are more complex at the interaction neighborhood scale, with the relationship
      among alien species richness and/or density and the density of indigenous species
      varying between habitats, being negative in some, but positive in others.
      Additional analyses demonstrated a strong influence of species identity, with
      negative relationships identified at the interaction neighborhood scale involving
      alien hypogastrurid springtails, a group known from elsewhere to have negative
      effects on indigenous species in areas where they have been introduced. By
      contrast, diversity relationships were positive with the other alien species.
      These results are consistent with both theory and previous empirical findings for
      other taxa, that interactions among indigenous and alien species change
      substantially with spatial scale and that environmental favorability may play a
      key role in explaining the larger scale patterns. However, they also suggest that
      the interactions may be affected by the identity of the species concerned,
      especially at the interaction neighborhood scale.

PMID- 21870619
TI  - Unequal resource allocation among colonies produced by fission in the ant
      Cataglyphis cursor.
AB  - How organisms allocate limited resources to reproduction is critical to their
      fitness. The size and number of offspring produced have been the focus of many
      studies. Offspring size affects survival and growth and determines offspring
      number in the many species where there is a trade-off between size and number.
      Many social insects reproduce by colony fission, whereby young queens and
      accompanying workers split off from a colony to form new colonies. The size of a
      new colony (number of workers) is set at the time of the split, and this may
      allow fine tuning size to local conditions. Despite the prevalence of colony
      fission and the ecological importance of social insects, little is known of
      colony fission except in honey bees. We studied colony fission in the ant
      Cataglyphis cursor. For clarity, "colony" and "nest" refer to colonies before and
      after colony fission, respectively (i.e., each colony fissions into several
      nests). The reproductive effort of colonies was highly variable: Colonies that
      fissioned varied markedly in size, and many colonies that did not fission were as
      large as some of the fissioning colonies. The mother queen was replaced in half
      of the fissioning colonies, which produced 4.0 +/- 1.3 (mean +/- SD) nests of
      markedly varied size. Larger fissioning colonies produced larger nests but did
      not produce more nests, and resource allocation among nests was highly biased.
      When a colony produced several nests and the mother queen was not replaced, the
      nest containing the mother queen was larger than nests with a young queen. These
      results show that the pattern of resource allocation differs between C. cursor
      and honey bees. They also suggest that C. cursor may follow a bet-hedging
      strategy with regard to both the colony size at which fission occurs and the
      partitioning of resources among nests. In addition, colony fission may be
      influenced by the age and/or condition of the mother queen, and the fact that
      workers allocating resources among nests have incomplete knowledge of the size
      and number of nests produced. These results show that the process of colony
      fission is more diverse than currently acknowledged and that studies of
      additional species are needed.

PMID- 21870620
TI  - Climate variability and spruce beetle (Dendroctonus rufipennis) outbreaks in
      south-central and southwest Alaska.
AB  - We used tree ring data (AD 1601-2007) to examine the occurrence of and climatic
      influences on spruce beetle (Dendroctonus rufipennis) outbreaks in south-central
      and southwest Alaska and found evidence of regional-scale outbreaks dating from
      the mid-1700s, related to climate variability at multiple temporal scales. Over
      interannual time scales (approximately 1-3 years), El Nino years, combined with
      severe late-summer drought, appeared to contribute significantly to spruce beetle
      outbreaks in the study area. Over multidecadal time scales (up to approximately
      40 years), cool-phase Pacific Decadal Oscillation (PDO) conditions tended to
      precede beetle outbreaks, regardless of the phase of El Nino-Southern Oscillation
      (ENSO). All sites showed low-severity disturbances attributed to spruce beetle
      damage, most notably during the 1810s. During other major periods of disturbance
      (i.e., 1870s, 1910s, 1970s), the effects of spruce beetle outbreaks were of
      moderate or higher severity. The highly synchronized timing of spruce beetle
      outbreaks at interannual to multidecadal scales, and particularly the association
      between cool-phase PDO conditions and beetle disturbance, suggests that climate
      (i.e., temperature, precipitation) is a primary driver of outbreaks in the study
      area. Our disturbance chronologies (mid-1700s to present) suggest that recent
      irruptions (1990s to present) in south-central and southwest Alaska are within
      the historical geographic range, but that outbreaks since the 1990s show greater
      spatiotemporal synchrony (i.e., more sites record high-severity infestations)
      than at any other time in the past approximatly 250 years.

PMID- 21870621
TI  - Substrate concentration and enzyme allocation can affect rates of microbial
      decomposition.
AB  - A large proportion of the world's carbon is stored as soil organic matter (SOM).
      However, the mechanisms regulating the stability of this SOM remain unclear.
      Recent work suggests that SOM may be stabilized by mechanisms other than chemical
      recalcitrance. Here, we show that the mineralization rate of starch, a plant
      polymer commonly found in litter and soil, is concentration dependent, such that
      its decomposition rate can be reduced by as much as 50% when composing less than
      approximately 10% of SOM. This pattern is largely driven by low activities of
      starch-degrading enzymes and low inducibility of enzyme production by microbial
      decomposers. The same pattern was not observed for cellulose and hemicellulose
      degradation, possibly because the enzymes targeting these substrates are
      expressed at constitutively high levels. Nevertheless, given the heterogeneous
      distribution of SOM constituents, our results suggest a novel low-concentration
      constraint on SOM decomposition that is independent of chemical recalcitrance.
      These results may help explain the stability of at least some SOM constituents,
      especially those that naturally exist in relatively low concentrations in the
      soil environment.

PMID- 21870622
TI  - Biogeochemistry of a temperate forest nitrogen gradient.
AB  - Wide natural gradients of soil nitrogen (N) can be used to examine fundamental
      relationships between plant-soil-microbial N cycling and hydrologic N loss, and
      to test N-saturation theory as a general framework for understanding ecosystem N
      dynamics. We characterized plant production, N uptake and return in litterfall,
      soil gross and net N mineralization rates, and hydrologic N losses of nine
      Douglas-fir (Pseudotsuga menziesii) forests across a wide soil N gradient in the
      Oregon Coast Range (U.S.A.). Surface mineral soil N (0-10 cm) ranged nearly three
      fold from 0.29% to 0.78% N, and in contrast to predictions of N-saturation
      theory, was linearly related to 10-fold variation in net N mineralization, from 8
      to 82 kg N.ha(-1) x yr(-1). Net N mineralization was unrelated to soil C:N, soil
      texture, precipitation, and temperature differences among sites. Net
      nitrification was negatively related to soil pH, and accounted for <20% of net N
      mineralization at low-N sites, increasing to 85-100% of net N mineralization at
      intermediate- and high-N sites. The ratio of net: gross N mineralization and
      nitrification increased along the gradient, indicating progressive saturation of
      microbial N demands at high soil N. Aboveground N uptake by plants increased
      asymptotically with net N mineralization to a peak of approximately 35 kg N.ha(
      1) x yr(-1). Aboveground net primary production per unit net N mineralization
      varied inversely with soil N, suggesting progressive saturation of plant N
      demands at high soil N. Hydrologic N losses were dominated by dissolved organic N
      at low-N sites, with increased nitrate loss causing a shift to dominance by
      nitrate at high-N sites, particularly where net nitrification exceeded plant N
      demands. With the exception of N mineralization patterns, our results broadly
      support the application of the N-saturation model developed from studies of
      anthropogenic N deposition to understand N cycling and saturation of plant and
      microbial sinks along natural soil N gradients. This convergence of behavior in
      unpolluted and polluted forest N cycles suggests that where future reductions in
      deposition to polluted sites do occur, symptoms of N saturation are most likely
      to persist where soil N content remains elevated.

PMID- 21870623
TI  - Nonredundancy in the dispersal network of a generalist tropical forest tree.
AB  - Plant species with generalized dispersal mutualisms are considered to be robust
      to local frugivore extinctions because of redundancy between dispersal agents.
      However, real redundancy can only occur if frugivores have similar foraging and
      ranging patterns and if fruit is a limiting resource. We evaluated the
      quantitative and qualitative contributions of seed dispersers for an endochorus
      mast-fruiting species, Prunus javanica (Rosaceae) in Khao Yai National Park,
      Thailand, to evaluate the potential redundancy of dispersers. Data were collected
      from tree watches, seed/fruit traps, and seed transects under and away from
      fruiting trees, feeding and seed deposition by gibbons (Hylobates lar), and
      evaluations of seed and first-year seedling survival. We identified three
      clusters of dispersers within the network. Most (>80%) frugivore species observed
      were small birds and squirrels that were not functional dispersers, dropping most
      seeds under or very near the tree crown, where seedling survival was ultimately
      nil. Monkeys (Macaca leonina) were low-quality, short-range dispersers, but they
      dispersed large numbers of seeds and were responsible for 67% of surviving first
      year seedlings. Gibbons and Oriental Pied Hornbills (Anthracoceros albirostris)
      handled few fruits, but they provided the highest quality service by carrying
      most seeds away from the canopy to medium and long distances, respectively.
      Although there was overlap in the deposition patterns of the functional
      dispersers, they displayed complementary, rather than redundant, roles in seed
      dispersal. Satiation of all functional dispersers further limited their capacity
      to "replace" one another. Redundancy must be evaluated at the community level
      because each type of disperser may shift to different species in the non-masting
      years of P. javanica. Our results underscore the need for research on broader
      spatial and temporal scales, which combines studies of dispersal and plant
      recruitment, to better understand mechanisms that maintain network stability.

PMID- 21870624
TI  - Contrasting effects of habitat loss and fragmentation on coral-associated reef
      fishes.
AB  - Disturbance can result in the fragmentation and/or loss of suitable habitat, both
      of which can have important consequences for survival, species interactions, and
      resulting patterns of local diversity. However, effects of habitat loss and
      fragmentation are typically confounded during disturbance events, and previous
      attempts to determine their relative significance have proved ineffective. Here
      we experimentally manipulated live coral habitats to examine the potential
      independent and interactive effects of habitat loss and fragmentation on
      survival, abundance, and species richness of recruitment-stage, coral-associated
      reef fishes. Loss of 75% of live coral from experimental reefs resulted in low
      survival of a coral-associated damselfish and low abundance and richness of other
      recruits 16 weeks after habitat manipulations. In contrast, fragmentation had
      positive effects on damselfish survival and resulted in greater abundance and
      species richness of other recruits. We hypothesize that spacing of habitat
      through fragmentation weakens competition within and among species. Comparison of
      effect sizes over the course of the study period revealed that, in the first six
      weeks following habitat manipulations, the positive effects of fragmentation were
      at least four times stronger than the effects of habitat loss. This initial
      positive effect of fragmentation attenuated considerably after 16 weeks, whereas
      the negative effects of habitat loss increased in strength over time. There was
      little indication that the amount of habitat influenced the magnitude of the
      habitat fragmentation effect. Numerous studies have reported dramatic declines in
      coral reef fish abundance and diversity in response to disturbances that cause
      the loss and fragmentation of coral habitats. Our results suggest that these
      declines occur as a result of habitat loss, not habitat fragmentation. Positive
      fragmentation effects may actually buffer against the negative effects of habitat
      loss and contribute to the resistance of reef fish populations to declines in
      coral cover.

PMID- 21870625
TI  - Calculating Ne and Ne/N in age-structured populations: a hybrid Felsenstein-Hill
      approach.
AB  - The concept of effective population size (Ne) was developed under a discrete
      generation model, but most species have overlapping generations. In the early
      1970s, J. Felsenstein and W. G. Hill independently developed methods for
      calculating Ne in age-structured populations; the two approaches produce the same
      answer under certain conditions and have contrasting advantages and
      disadvantages. Here, we describe a hybrid approach that combines useful features
      of both. Like Felsenstein's model, the new method is based on age-specific
      survival and fertility rates and therefore can be directly applied to any species
      for which life table data are available. Like Hill, we relax the restrictive
      assumption in Felsenstein's model regarding random variance in reproductive
      success, which allows more general application. The basic principle underlying
      the new method is that age structure stratifies a population into winners and
      losers in the game of life: individuals that live longer have more opportunities
      to reproduce and therefore have a higher mean lifetime reproductive success. This
      creates different classes of individuals within the population, and grouping
      individuals by age at death provides a simple means of calculating lifetime
      variance in reproductive success of a newborn cohort. The new method has the
      following features: (1) it can accommodate unequal sex ratio and sex-specific
      vital rates and overdispersed variance in reproductive success; (2) it can
      calculate effective size in species that change sex during their lifetime; (3) it
      can calculate Ne and the ratio Ne/N based on various ways of defining N; (4) it
      allows one to explore the relationship between Ne and the effective number of
      breeders per year (Nb), which is a quantity that genetic estimators of
      contemporary Ne commonly provide information about; and (5) it is implemented in
      freely available software (AgeNe).

PMID- 21870626
TI  - Can entropy maximization use functional traits to explain species abundances? A
      comprehensive evaluation.
AB  - Entropy maximization (EM) is a method that can link functional traits and
      community composition by predicting relative abundances of each species in a
      community using limited trait information. We developed a complementary suite of
      tests to examine the strengths and limitations of EM and the community-aggregated
      traits (CATs; i.e., weighted averages) on which it depends that can be applied to
      virtually any plant community data set. We show that suites of CATs can be used
      to differentiate communities and that EM can address the classic problem of
      characterizing ecological niches by quantifying constraints (CATs) on complex
      trait relationships in local communities. EM outperformed null models and
      comparable regression models in communities with different levels of dominance,
      diversity, and trait similarity. EM predicted well the abundance of the dominant
      species that drive community-level traits; it typically identified rarer species
      as such, although it struggled to predict the abundances of the rarest species in
      some cases. Predictions were sensitive to choice of traits, were substantially
      improved by using informative priors based on null models, and were robust to
      variation in trait measurement due to intraspecific variability or measurement
      error. We demonstrate how similarity in species' traits confounds predictions and
      provide guidelines for applying EM.

PMID- 21870627
TI  - Orchids do not pay costs at emergence for prolonged dormancy.
AB  - In plants, prolonged dormancy is often considered a response to resource
      depletion or environmental stress that comes at a fitness cost. However, apparent
      costs of dormancy could reflect the state in which plants entered dormancy,
      rather than effects of dormancy per se. We tested this hypothesis for a
      terrestrial orchid, Epipactis atrorubens, by analyzing differences in vital rates
      of dormant and emergent plants using generalized linear mixed models, applied to
      eight years of demographic data. Dormant E. atrorubens plants did not form one
      homogeneous stage class. Instead, the vital rates of dormant plants mirrored
      performance of plants in their life stage before dormancy. Plants emerging from
      dormancy were slightly (albeit only marginally statistically significantly)
      larger than plants transitioning from the matching aboveground stage class,
      especially for smaller and younger stage classes. Because small plants were most
      likely to go dormant, plants emerging from dormancy were also smaller than
      average, if one were to compare all previously dormant plants to all previously
      emergent plants. Therefore, misclassifying all dormant plants into a single stage
      class changes whether we view dormancy as intrinsically costly, in terms of
      future performance upon emergence. We suggest that prolonged dormancy may be a
      form of phenotypic plasticity in which plants distribute their performance and
      reproductive effort through time, rather than a simple stress response.

PMID- 21870628
TI  - Alzheimer's disease: current status of etiopathogenesis and therapeutic
      strategies.
AB  - Alzheimer's Disease (AD) is one of the most common age-related neurodegenerative
      diseases. It is the most prevalent form of dementia, a general term for memory
      loss. It is characterized by progressive cognitive dysfunction, various
      behavioral and neuro-psychiatric disturbances that seriously interfere with daily
      life. Scientists have identified factors that appear to play a role in the
      development of AD but no definitive causes have been found for this complex
      disorder. The pathogenesis of Alzheimer's disease is highly complex. While
      several pathologies characterize this disease, amyloid plaques and
      neurofibrillary tangles are hallmark neuropathological lesions in AD brain.
      Current AD therapies are merely palliative and only temporarily slow cognitive
      decline and treatments that address the underlying pathologic mechanisms of AD
      are still lacking. In this review, we focus on the current aspects of AD ranging
      from the key risk factors for AD, the underlying pathogenic events and the novel
      medications including disease-modifying properties.

PMID- 21870629
TI  - A study of yield and yield components of different ornamental pepper (Capsicum
      sp.) species and lines in cukurova ecological conditions.
AB  - This study examined some phenological, morphological and pomological features of
      different ornamental pepper (Capsicum sp.) species and lines under the conditions
      of Cukurova Region, Turkey. The field trials used a randomized complete block
      design with three replications. Different ornamental pepper species and lines
      varied depending on testing years, in terms of plant height (cm), the number of
      branches (number/plant), the number of fruits (number/plant), the weight of fresh
      fruit (g plant(-1)), the yield of fresh fruit (kg ha(-1)) and the breadth and
      length of fruit. Fresh yields of different ornamental pepper species and lines
      varied between 9412 - 24418 kg ha(-1) in the testing years. The highest fresh
      yield was observed from line C. frutescens 26 (24418 kg ha(-1)). It was
      determined that the fresh yield from the first harvest was higher than the
      others.

PMID- 21870630
TI  - The effects of low calorie diet with soy protein on cardiovascular risk factors
      in hyperlipidemic patients.
AB  - Serum lipid abnormalities are an established risk factor for cardiovascular
      disease in hyperlipidemic patients. Because of the side effect of long-term
      medications in these patients, soy protein, as a part of healthy diet, may
      improve their lipid profile. The purpose of this study was to determine the
      effect of soy protein with low-calorie diet on lipid profiles in hyperlipidemic
      patient. Fifty two hyperlipidemic patients of both sex and age range of 25-65
      years were participated. The patients received low-calorie diet based on 1400
      kcal energy 18% protein, 24% fat and 58% carbohydrate per day for 4 weeks. The
      treatment group received low-calorie diet including (30 g day(-1)) of soy
      protein. Blood samples were obtained after an overnight (12 h) fasting period
      before the study and in the last day of the intervention period. Anthropometric
      indices and levels of serum triacylglycerol, total cholesterol, low-density
      lipoprotein and high-density lipoprotein were measured before and after the
      intervention. In groups, weight, body mass index, waist and hip circumferences
      were significantly reduced (p<0.05) after four weeks. In comparison with control
      group, the results of treatment of soy protein with low-calorie diet showed that
      at the end of 4th week serum low-density lipoprotein was significantly (p<0.05)
      decreased while an insignificant reduction was seen in total cholesterol. This
      study suggest that soy protein with low calorie diet for 4 weeks treatment may be
      safe and effective alternative therapy for diminished the cardiovascular risk
      factors in hyperlipidemic patients.

PMID- 21870631
TI  - Evaluation of aluminium, manganese, copper and selenium effects on human islets
      amyloid polypeptide hormone aggregation.
AB  - Islet amyloid formation causes destruction of insulin-producing beta-cells of the
      pancreas. The subsequent lack of insulin leads to increased blood and urine
      glucose. In this research, the fluorimetric assay was used to examine the effects
      of aluminium and some nutritionally essential trace elements including,
      manganese, copper and selenium on amyloid formation of human peptide of amylin
      under near-physiological circumstances. Results obtained from in vitro study
      showed that after 120 h incubation by shaker incubator in 37 degrees C, copper
      and selenium at 8 microM inhibited amylin 8 microM from amyloid fibril formation
      by 22.1 and 11.3%, respectively (p<0.05) while the similar values of either
      aluminium and manganese promoted the formation of beta-pleated sheet structure by
      19.3 and 13.2% respectively (p<0.05). If islet amyloid is cytotoxic to beta-cells
      then copper and selenium may be able to protect these cells against degeneration
      in diabetic patients especially in type 2 diabetes mellitus.

PMID- 21870632
TI  - Seasonal trends in epidemiological and entomological profiles of malaria
      transmission in North Central Nigeria.
AB  - The influence of seasonal changes on epidemiological and entomological indices of
      malaria transmission in North Central Nigeria was elucidated in a series of
      studies carried out between January 2004 and December 2009. The climate in the
      study area was divided into three seasonal periods namely, rainy (May-October),
      dry (December-March) and transitional (April and November), during which larval
      and adult anopheline mosquito collections were carried out and assessed for
      densities, sporozoite infection and parity rates and potentials for malaria
      transmission. The results indicated that the climate in the study area was
      clearly seasonal, with close similarities in the patterns of distribution of the
      climatic factors in the study sites. Mosquito densities, both at the adult and
      larval stages (i.e., 29.35 +/- 5.10 adult mosquitoes/man/night and 10.36 +/- 3.34
      larvae/dip, respectively), were significantly (p<0.05) highest during the rainy
      season. However, while the former varied significantly in the three seasonal
      periods, the latter was not significantly different during the dry and
      transitional seasons. Malaria transmission risks, in terms of sporozoite rates
      and entomological inoculation rates, was significantly (p<0.05) least in the dry
      season (i.e., 2.89 +/- 1.25% and 0.37 +/- 0.21 infective bite/man/night,
      respectively) but the two variables were not significantly (p>0.05) different
      during the transitional and rainy seasons. Adult mosquito daily survival rate and
      adult longevity were least in the dry season (26.52 +/- 11.80% and 6.80 days,
      respectively) and significantly (p<0.05) highest during the rainy season (72.28
      +/- 4.00% and 16.95 +/- 4.20 days, respectively). Parous rates of the mosquitoes
      and duration of sporogony had distinct distribution pattern from the other
      variables investigated. While, significantly highest parous rates were recorded
      in the transitional season (86.00 +/- 4.30%), duration of sporogony was not
      significantly (p>0.05) different during the three seasons. The epidemiology of
      urban malaria in North Central Nigeria was discussed from the view points of the
      these results and concluded that the findings should promote the development of
      informed temporally-targeted vector control programs for the area.

PMID- 21870633
TI  - Effects of salicylic acid on growth, biochemical constituents in pepper (Capsicum
      annuum L.) seedlings.
AB  - In the present study, the effect of different concentrations of salicylic acid
      which is an endogenous organic acid in plants and which is commonly cited as a
      hormone, on the growth and some other parameters of pepper (Capsicum annuum L.
      cv.) seedlings was investigated. The solutions were applied to the roots of
      seedlings using hydroponic method. In general, 1.5 mM concentration of salicylic
      acid had a stimulating effect while 5 and 10 mM concentrations had varying
      degrees of inhibitive effects on the seedlings. Although 0.3 mM SA application
      produced prominent results in the case of all parameters, the difference was not
      found statistically significant. The inhibitive effect produced by high SA was
      found much more dominant than the stimulating effect of low SA concentrations.
      Thus, it was established that SA had a bidirectional physiological effect on the
      seedlings in a concentration-dependent manner.

PMID- 21870634
TI  - Antimicrobial activity of Hedeoma drummondii against opportunistic pathogens.
AB  - Hedeoma drummondii is a medicinal plant with diverse properties; however,
      validations of its medicinal uses are scarce. To evaluate its antimicrobial
      properties H. drummondii, was tested against opportunistic pathogens of medical
      importance. Antimicrobial tests were performed by the microdilution method in
      order to determine the Minimal Inhibitory Concentration (MIC) for each extract.
      Extracts of this plant showed relevant antimicrobial activity, results revealed
      that the hexanic extract has stronger activity and broader spectrum compared to
      acetone and methanol extracts. The activity of hexanic extract may be attributed
      mainly to the presence of the monoterpenes pulegone and menthol. In conclusion,
      the hexanic extract possess relevant antibacterial properties which suggests that
      H. drummondii have bioactive principles; these new data provide scientific
      support for the use of this plant in traditional medicine, particularly for
      gastrointestinal diseases.

PMID- 21870635
TI  - Male fertility is in the bones: first evidence that skeleton plays a role in
      reproduction.

PMID- 21870636
TI  - Brain function linked to birth size; study sheds light on mental health problems
      later in life.

PMID- 21870637
TI  - Regrowing hair: researchers may have accidentally discovered a solution.

PMID- 21870638
TI  - Water softeners not found to improve childhood eczema.

PMID- 21870639
TI  - Sub-Saharan Rubiaceae: a review of their traditional uses, phytochemistry and
      biological activities.
AB  - Rubiaceae family is a large family of 630 genera and about 13000 species found
      worldwide, especially in tropical and warm regions. These plants are not only
      ornamental but they are also used in African folk medicine to treat several
      diseases. Based on online published data and library bibliographic research, we
      herein reported accumulated information related to their traditional usages in
      sub-Saharan traditional medicine, their chemical composition and the screened
      pharmacological activities. Indeed, more than 60 species are used for more than
      70 medicinal indications including malaria, hepatitis, eczema, oedema, cough,
      hypertension, diabetes and sexual weakness. Through biological screening
      following leads supplied with traditional healers, many of these plants exhibited
      antimalarial, antimicrobial, antihypertension, antidiabetic, antioxidant and anti
      inflammatory activities. Bioactive compounds including indole alkaloids,
      terpenoids and anthraquinones have been isolated from these bioguided
      fractionation studies. It is evidence that great attention has been paid to
      species such as Nauclea latifolia, Morinda lucida, Mitragyna inermis and
      Crossopteryx febrifuga; however, several compounds should be waiting to be
      discovered since none of these plants has been systematically investigated for
      its biochemical composition. According the current global health context with the
      recrudescence of HIV, much effort should be oriented towards this virus when
      screening Rubiaceae.

PMID- 21870640
TI  - Central dogma in thyroid dysfunction: a review on structure modification of TSHR
      as a cornerstone for thyroid abnormalities.
AB  - Thyroid stimulating hormone receptor (TSHR) is a vital thyrocyte membrane protein
      in the thyroid gland. Thyroid Stimulating Hormone (TSH) which is a pituitary
      hormone is the main stimulator of thyroid gland to produce thyroid hormones, it
      binds with high affinity to the TSHR through weak bonds including hydrophobic,
      ionic, hydrogen bonds and trigger the initial steps in thyroid gland stimulation
      to produce the related hormones. This study was carried out at department of
      biochemistry of Golestan university of medical sciences. All the related articles
      related to TSHR modification happened due to mutations and any other alterations
      which affect the level of TSH-TSHR complex were studied and the main points were
      extracted out of the pile of information and were organized as present review.
      TSH-TSHR is the initial and vital step of a long process of thyroid hormone
      production within the thyroid gland. Any alteration on the TSH-TSHR affinity
      which may happen due to the direct effect of TSHR modification eventually lead to
      the serious adverse effects of either hypothyroidism or hyperthyroidism if the
      TSH-TSHR level are suppressed or elevated, respectively. The prime cause of the
      thyroid disorders relay on the possible modification on the biochemical structure
      of TSHR with subsequent alteration on the level of TSH-TSHR complex. TSHR
      mutation accompanied by biochemical modification, unable it to bind properly to
      TSH. In some other conditions such mutation leave a TSHR with either of higher
      affinity towards to TSH or even TSHR which can be activated in the absence of
      TSH. The structural modification of TSHR and alteration in the level of TSH-TSHR
      in the thyroid gland eventually lead to thyroid disorders either of
      hypothyroidism or hyperthyroidism.

PMID- 21870641
TI  - Macro invertebrate community from Sonamarg streams of Kashmir Himalaya.
AB  - This study analyses a macroinvertebrate community survey for River Sindh and its
      tributary including Baltal, Yashmarg, Sonamarg and Thajwas Grar considering the
      extreme hydrological conditions linked with the seasonal low-flow period typical
      for some streams in this area. This study attempts to provide an overview of the
      macro invertebrate assemblages and physico-chemical variables of the River Sindh
      and its important tributary. Four study sites were selected from the River Sindh
      and its tributary including Baltal, Yashmarg, Sonamarg and Thajwas Grar for
      studying the ecological distribution of Macroinvertebrate assemblages. Totally,
      33 taxa of macroinvertebrates were recorded from the two streams belonging to
      Mollusca-3 (Gastropoda-2 and Bivalvia-1), Annelida-1 and Arthropoda-29 (Insecta
      29). Among insects Ephemeroptera (7), Trichoptera (6) and Diptera (13) dominated.
      Except Yashmrag all sites were found devoid of annelids while as the mollusks
      were found absent at Sonamarg. Highest values of Shannon Weiner Index were found
      at Yashmarg (2.42) and lowest at Sonamarg (1.99) while as highest and lowest
      Sorensen's similarity coefficient were found between Baltal/Thajwas Grar (0.68)
      and Yashmarg/Thajwas Grar (0.39), respectively. A perusal of the data on physico
      chemical characteristics showed that these streams were hard water type with high
      dissolved oxygen content. The ionic composition of the stream waters revealed the
      predominance of bicarbonate and calcium. Insecta dominated both qualitatively as
      well as quantitatively and the study revealed that the substrate compositions
      dominated by gravel, pebble and leaf litters are primary determinants of the
      invertebrate community structure recording maximum species diversity and
      abundance. Sample locations impacted by Amarnath yatris pilgrimage comparatively
      reflected slightly higher increase in nutrients than Thajwas Grar almost devoid
      of pilgrimage effect.

PMID- 21870642
TI  - Early detection of immunization: a study based on an animal model using 1H
      nuclear magnetic resonance spectroscopy.
AB  - Vaccines require a period of at least three months for clinical trials, hence a
      method that can identify elicitation of immune response a few days after the
      first dose is a necessity. Evolutionary variable selections are modeling
      approaches for proper manipulation of available data which were used to set up an
      animal model for classification of time dependent 1HNMR metabolomic profiles and
      pattern recognition of fluctuations of metabolites in two groups of male rabbits.
      One group of rabbits was immunized with human red blood cells and the other used
      as control. Blood was obtained every 48 h from each rabbit for a period of six
      weeks and the serum monitored for antibodies and metabolites by 1HNMR spectra.
      Evaluation of data was carried out using orthogonal signal correction followed by
      principal component analysis and partial least square. A neural network was also
      set up to predict immunization profiles. A distinct separation in patterns of
      significant metabolites was obtained between the two groups, just a few days
      after the first and the second dose. These metabolites were used as targets of
      neural networks where each sample was used as test, validation and training and
      their quantitative influence predicted by regression. This model could be used
      for prediction of immunization in rabbits a few days after the first dose with
      96% accuracy. Similar animals and human vaccine trials would assist greatly in
      reaching early conclusions in advance of the usual two month immunization
      schedule; resulting in an appreciable saving of cost and time.

PMID- 21870643
TI  - Novel chitinase genes from metagenomic DNA prepared from marine sediments in
      southwest Japan.
AB  - Chitinase degrades chitin which comprises an important source of carbon and
      nitrogen in the marine environment. The aim of this study was to evaluate the
      population of chitinases in the marine sediments in southwest Japan. We collected
      marine sediments from eutrophic inner bay and offshore. Chitin-degrading bacteria
      were enriched from both sediments. Metagenomic DNA was isolated from the enriched
      chitin-degrading bacterial cell culture. At the same time, 25 chitin-degrading
      bacteria were isolated from the enriched culture. Partial fragments of chitinase
      genes were successfully amplified with degenerate primers designed for the
      glycoside hydrolase 18 family. We analyzed chitinase gene sequences of about 500
      clones from metagenomic DNA prepared from chitin-degrading bacteria. Based on
      translated amino acid sequences, chitinases were grouped into five groups.
      Chitinases in groups II and III was most abundant and close to chitinase genes of
      several species of proteobacteria. On the other hand, chitinases in groups I, IV
      and V were unique and distinct from the known chitinases. These results indicate
      that the marine sediments used in this study contain diversity of chitinase
      genes.

PMID- 21870644
TI  - Homozygous deletion of the FHIT gene, p21WAF1 protein expression and apoptosis in
      bilharzial bladder cancer.
AB  - The FHIT gene alterations may occur as early consequences for the urinary bladder
      cancer. The present study aimed to identify and analyze the role of homozygous
      deletion (HZD) and transcriptional alterations of fragile histidine triad (FHIT)
      gene in the development and progression of bilharzial bladder cancer in Egyptian
      patients. The possible associations between FHIT abnormalities and some clinical
      variables that have prognostic impact in bilharzial bladder cancer patients were
      determined. In addition, the relations between homozygous deletion (HZD) of FHIT
      gene, FHIT protein, p21WAF1 expression and apoptosis were demonstrated. We
      investigated 42 human bladder cancer and 10 normal adjacent tissues as a control
      group. HZD of the FHIT gene, FHIT protein, p21 protein and apoptosis were
      assessed by PCR, immunohistochemistry and DNA ladder method, respectively. FHIT
      HZD deletions have expressed a significant correlation with FHIT protein (p< or
      =0.04), p21WAF1 protein expression (p< or =0.005) and apoptosis (p< or =0.03). On
      the other side, no correlations were detected between FHIT homozygous deletions
      and tumor type, tumor grade and gender. Therefore, the FHIT gene deletions could
      be important in the development and/or progression of urinary bladder cancers and
      may be used as an independent prognostic indicator for the clinical outcome in
      patients with these tumors.

PMID- 21870645
TI  - Effects of taurine on glutathione peroxidase, glutathione reductase and reduced
      glutathione levels in rats.
AB  - The aim of the present study is to investigate the effects of oral administration
      of taurine on endogenous glutathione peroxidase (GPx) and Glutathione Reductase
      (GR) activities and reduced glutathione (GSH) level in normal rats. Normal saline
      (Group I) or 5% taurine in normal saline was administered in dose of 50 mg (Group
      II), 250 mg (Group III) or 500 mg kg(-1) of body weight (Group IV) through
      intragastric intubation for 60 days. GPx and GR enzyme activities and GSH and
      taurine levels were determined in liver, heart, stomach, kidney and plasma of
      normal Wistar rats. GPx activity showed an increase in liver, heart, stomach and
      plasma. GR activity increased in kidney and decreased in liver and plasma. GSH
      levels increased in liver, stomach and decreased in kidney. Liver showed an
      increase and heart, stomach and kidney a decrease in taurine level in taurine
      administered rats when compared to control rats. The results varied from organ to
      organ and the observed variations among organs might be related to their
      respective enzymatic, non-enzymatic antioxidant potential and its functions. From
      the present study it may be concluded that long term oral administration of
      taurine affects GPx, GR and GSH levels in normal rats.

PMID- 21870646
TI  - Production and partial characterization of uric acid degrading enzyme from new
      source Saccharopolyspora sp. PNR11.
AB  - The strain PNR11 was isolated from gut of termite during the screening for uric
      acid degrading actinomyces. This strain was able to produce an intracellular
      uricase when cultured in fermentation medium containing uric acid as nitrogen
      source. Base on its morphological characters and 16S rDNA sequence analysis, this
      strain belong to the genus Saccharopolyspora. This is the first report ofuricase
      produced from the genus Saccharopolyspora. The aim of this study was to
      investigate the effects of different factors on uricase production by new source
      of Saccharopolyspora. Saccharopolyspora sp. PNR11 was cultured in production
      medium in order to determine the best cultivation period. The result showed that
      the time period required for maximum enzyme production was 24 h on a rotary
      shaker operating at 180 rpm. Optimized composition of the production medium
      consisted of 1% yeast extract, 1% maltose, 0.1% K2HPO4, 0.05% MgSO4 7H2O, 0.05%
      NaCl and 1% uric acid. The optimum pH and temperature for uricase production in
      the optimized medium were pH 7.0 and 30 degrees C, respectively. When the strain
      was cultured at optimized condition, the uricase activity reached to 216 mU mL(
      1) in confidential level of 95%. The crude enzyme had an optimum temperature of
      uricase was 37 degrees C and it was stable up to 30 degrees C at pH 8.5. The
      optimum pH ofuricase was 8.5 and was stable in range of pH 7.0-10.0 at 4 degrees
      C. This strain might be considered as a candidate source for uricase production
      in the further studies. Present finding could be fulfill the information
      ofuricase produce from actinomycetes.

PMID- 21870647
TI  - Optimum dietary protein requirement of Malaysian mahseer (Tor tambroides)
      fingerling.
AB  - The optimum dietary protein requirement of the Malaysian mahseer (Tor tambroides)
      fingerlings was determined in this study. In this completely randomized designed
      experiment, formulated diets of five levels of dietary protein (30, 35, 40, 45
      and 50%) were tested on the T. tambroides fingerlings (initial body weight of
      5.85 +/- 0.40 g), reared in aquarium fitted with a biofiltering system. The
      fingerlings were fed twice daily at 5% of biomass. The fingerling body weight and
      total length was taken at every two weeks. Mortality was recorded daily. The
      dietary protein had significant effects on the body weight gain and Specific
      Growth Rate (SGR) of the fingerlings. The body weight gain and SGR of fingerlings
      fed with the diet with the dietary protein level of 40% was significantly higher
      (p<0.05) than that of 30, 35 and 50%. The feed conversion ratio of the 40%
      dietary protein was the significantly lowest at 2.19 +/- 0.163. The dietary
      protein level of 40% was the most optimum for T. tambroides fingerlings.

PMID- 21870648
TI  - Effect of ozone and potassium lactate on lipid oxidation and survival of
      Salmonella typhimurium on fresh pork.
AB  - The objective of this research was to evaluate the effect of ozone gas and
      potassium lactate on lipid oxidation and survival of Salmonella typhimurium on
      fresh pork. A total of 144 samples of fresh pork samples were cut into pieces
      approximately (8x5x0.6) cm in size, then (0, 2 and 4%) potassium lactate (KL),
      inoculated with S. typhimurium was applied by spreading a 0.5 mL cell suspension
      over each sample. The pork samples were then packed in (6"x8") airtight
      polyethylene bags with a thickness of 87.5 microm and a volume of 3.5 L with and
      without ozone. Ozone gas was injected into the plastic bags at a rate of 0, 200,
      500 and 1,000 mg h(-1) and the samples later stored at 8 degrees C. Thio
      barbituric Acid Reactive Substance (TBARS) and microbial loads were determined on
      days 0, 5, 10 and 15. Data was statistically analyzed using SPSS software and
      differences among means detected at the 0.5% confident level using the Scheffe's
      test. Samples treated with 2 and 4% KL had significantly (p<0.01) lower TBARS
      value than non-treated samples. Combination of ozone and KL showed inhibitory
      effects on S. typhimurium in samples. S. typhimurium was sensitive to 4% KL with
      and without ozone. At 1,000 mg h(-1), ozone improved KL inhibitory effect on S.
      typhimurium. Ozone and KL are potential substances for inhibition of S.
      typhimurium.

PMID- 21870649
TI  - Sewage water bacteria fills 'missing link' in early evolution of life on Earth.

PMID- 21870650
TI  - Finger-trap tension stabilizes cell's chromosome-separating machinery.

PMID- 21870651
TI  - Diabetes drug could work against Alzheimer's, animal study suggests.

PMID- 21870652
TI  - Danger of cancerous tissue development in chromosomal abnormalities.

PMID- 21870653
TI  - Mystery of how fleas jump resolved after 44 years.

PMID- 21870654
TI  - JPEG for the mind: how the brain compresses visual information.

PMID- 21870655
TI  - Experts urge even greater caution in use of X-rays during pregnancy and infancy.

PMID- 21870656
TI  - New way to attack pathogens: RNA recycling system gone awry brings MRSA to a
      halt.

PMID- 21870657
TI  - Salivary glands as organs of immunity: new research makes oral immunization
      easier to swallow.

PMID- 21870658
TI  - Newly discovered squid pheromone sparks extreme aggression on contact.

PMID- 21870659
TI  - Biologists unlock chemical clues to courtship in swordtail fish urine.

PMID- 21870660
TI  - Natural toxin implicated as triggering Parkinson's disease.

PMID- 21870661
TI  - Scientists hope to cut years off development time of new antibiotics.

PMID- 21870662
TI  - Health emergencies in large populations: a disaster medicine learning experience.
AB  - The Health Emergencies in Large Populations course, organized by the
      International Committee of the Red Cross and Red Crescent Societies, is delivered
      in a decentralized manner by a number of academic centers around the world. It
      was one of the first formal educational opportunities developed for those in
      humanitarian assistance organizations, and its initial aim was to upgrade
      professionalism in humanitarian assistance programs conducted in emergency
      situations. This article summarizes the history and describes the current
      content, structure, and costs of the course.

PMID- 21870663
TI  - Bioterrorism--a health emergency: do physicians believe there is a threat and are
      they prepared for it?
AB  - OBJECTIVE: To determine whether bioterrorism training provided increased
      awareness and understanding of bioterrorism and to assess physicians' beliefs
      about the threat of bioterrorism and how it impacts on preparedness. DESIGN: This
      is a retrospective review of data obtained from a bioterrorism training grant.
      Data were obtained from a postevaluation form completed by trainees with an 80
      percent return rate. The Institutional Review Board approved this study. Informed
      consent was not required as data were deidentified and demographic information
      regarding study subjects was not used. SETTING: The Department of Family Medicine
      within the University of Medicine and and Dentistry of New Jersey, School of
      Osteopathic Medicine in Stratford, NJ, conducted the training and follow-up
      study. PARTICIPANTS: The bioterrorism preparedness training was targeted to
      physicians, residents, and third- and fourth-year medical students in New Jersey.
      There were 578 trainees; however, responses to each question were varied. OUTCOME
      MEASURES: Trainees were asked to complete an evaluation form. Specific questions
      were selected from the form. Frequency statistics were used to describe responses
      to the questions. RESULTS: Ninety-four percent of the respondents agreed that the
      bioterrorism training increased their awareness and/or understanding of
      bioterrorism; however, only 49 percent believe there is a high probability that a
      bioterrorism event or other health emergency will occur in the near future in New
      Jersey, and 42 percent considered themselves prepared to respond as a healthcare
      professional to a bioterrorism event. CONCLUSIONS: Physicians in New Jersey
      increased their awareness and understanding of bioterrorism through training.
      However, concerns remain that a physician's belief in a low threat of
      bioterrorism translates into a low need for bioterrorism preparedness training.

PMID- 21870664
TI  - WiFi RFID demonstration for resource tracking in a statewide disaster drill.
AB  - OBJECTIVE: To investigate the capabilities of Radio Frequency Identification
      (RFID) tracking of patients and medical equipment during a simulated disaster
      response scenario. DESIGN: RFID infrastructure was deployed at two small rural
      hospitals, in one large academic medical center and in two vehicles. Several item
      types from the mutual aid equipment list were selected for tracking during the
      demonstration. A central database server was installed at the UC Davis Medical
      Center (UCDMC) that collected RFID information from all constituent sites. The
      system was tested during a statewide disaster drill. During the drill, volunteers
      at UCDMC were selected to locate assets using the traditional method of locating
      resources and then using the RFID system. RESULTS: This study demonstrated the
      effectiveness of RFID infrastructure in real-time resource identification and
      tracking. Volunteers at UCDMC were able to locate assets substantially faster
      using RFID, demonstrating that real-time geolocation can be substantially more
      efficient and accurate than traditional manual methods. A mobile, Global
      Positioning System (GPS)-enabled RFID system was installed in a pediatric
      ambulance and connected to the central RFID database via secure cellular
      communication. This system is unique in that it provides for seamless region-wide
      tracking that adaptively uses and seamlessly integrates both outdoor cellular
      based mobile tracking and indoor WiFi-based tracking. CONCLUSIONS: RFID tracking
      can provide a real-time picture of the medical situation across medical
      facilities and other critical locations, leading to a more coordinated deployment
      of resources. The RFID system deployed during this study demonstrated the
      potential to improve the ability to locate and track victims, healthcare
      professionals, and medical equipment during a region-wide disaster.

PMID- 21870666
TI  - Transportation resource requirements for hospital evacuation.
AB  - Hospitals are physical structures with the same risk as other large buildings;
      the physical plant is vulnerable to acts of nature and man. When hospitals need
      to evacuate the patient population, logistical support for patient transport will
      be required. However, a disaster impacting a hospital will likely also affect the
      surrounding community, and transport resources such as ambulances may be limited
      as they will also be needed to support the community response. To determine the
      most efficient deployment of limited transportation resources, a hospital survey
      was designed specifically to assess information on hospital occupancy and patient
      transportation needs. Information was obtained from 62 hospitals within Los
      Angeles County and was used to establish a tool for determining transportation
      requirements in the event ofa hospital evacuation. This survey demonstrated that
      approximately 20 percent of hospital inpatients could be discharged to home
      within a few hours, about 40 percent of hospital inpatients could be transported
      via vans, buses, or private cars; and the remaining 40 percent would need
      ambulance transportation for evacuation. Additionally, the survey provides
      information about the distribution of emergency department and intensive care
      unit patients and the resources they would require during a hospital evacuation.

PMID- 21870665
TI  - Experimental induction of psychogenic illness in the context of a medical event
      and media exposure.
AB  - OBJECTIVES: Mass psychogenic illness can be a significant problem for triage and
      hospital surge in disasters; however, research has been largely limited to
      posthoc observational reports. Reports on the impact of public media during a
      disaster have suggested both salutary as well as iatrogenic psychological
      effects. This study was designed to determine if psychogenic illness can be
      evoked and if media will exacerbate it in a plausible, controlled experiment
      among healthy community adults. METHODS: A randomized controlled experiment used
      a simulated biological threat and elements of social contagion--essential
      precipitants of mass psychogenic illness. Participants were randomly assigned to
      one of three groups: no-intervention control group, psychogenic illness induction
      group, or psychogenic illness induction plus media group. Measures included three
      assessments of symptom intensity, heart rate, blood pressure, as well as
      questionnaires to measure potential psychogenic illness risk factors. RESULTS:
      The two psychogenic induction groups experienced 11 times more symptoms than the
      control group. Psychogenic illness was observed in both men and women at rates
      that were not significantly different. Higher rates of lifetime history of
      traumatic events and depression were associated with greater induction of
      illness. Media was not found to exacerbate symptom onset. CONCLUSIONS:
      Psychogenic illness relevant to public health disasters can be evoked in an
      experimental setting. This sets the stage for further research on psychogenic
      illness and strategies for mitigation.

PMID- 21870668
TI  - Advances in adolescent research in the Chinese culture: reflections and future
      research directions.

PMID- 21870667
TI  - Pandemic influenza and major disease outbreak preparedness in US emergency
      departments: a selected survey of emergency health professionals.
AB  - OBJECTIVE: To assess the level of pandemic preparedness at emergency departments
      (EDs) around the country and to better understand current barriers to
      preparedness in the United States represented by health professionals in the
      American College of Emergency Physician (ACEP) Disaster Medicine Section (DMS).
      METHODS, DESIGN, and SETTING: A cross-sectional survey of ACEP DMS members was
      performed. A total of 300 members were surveyed both via e-mail and with paper
      surveys during the 2009 ACEP Scientific Assembly DMS Meeting. An optional
      comments section was included for section members'perspectives on barriers to
      preparedness. A 15-item pandemic preparedness score was calculated for each
      respondent based on key preparedness indicators as defined by the authors.
      Results were analyzed with descriptive statistics, Chi2 analysis, Cochran
      Armitage trend test, and analysis of variance. Free text comments were coded and
      subjected to frequency-based analysis. RESULTS: A total of 92 DMS members
      completed the survey with a response rate of31 percent. Although 85 percent of
      those surveyed indicated that their hospital had a plan for pandemic influenza
      response and other infectious disease threats, only 68 percent indicated that
      their ED had a plan, and 52 percent indicated that their hospital or ED had
      conducted disaster preparedness drills. Only 57 percent indicated that there was
      a plan to augment ED staff in the event of a staffing shortage, and 63 percent
      indicated that there were adequate supplies of personal protective equipment.
      While 63 percent of respondents indicated that their ED had a plan for
      distribution of vaccines and antivirals, only 32 percent ofEDs had a plan for
      allocation of ventilators. A total of 42 percent of respondents felt that their
      ED was prepared in the event of a pandemic influenza or other disease outbreak,
      and only 35 percent felt that their hospital was prepared. The average pandemic
      preparedness score among respondents was 8.30 of a total of 15. Larger EDs were
      more likely to have a higher preparedness score (p=0.03) and more likely to have
      a pandemic preparedness plan (p=0.037). Some major barriers to preparedness cited
      by section members included lack of local administration support, challenges in
      funding, need for dedicated disaster preparedness personnel, staffing shortages,
      and a lack of communication among disaster response agencies, particularly at the
      federal level. CONCLUSIONS: There appear to be significant gaps in pandemic
      influenza and other infectious disease outbreak planning among the hospitals
      where ACEP DMS members work. This may reflect a broader underlying inadequacy of
      preparedness measures.

PMID- 21870669
TI  - Elder lifelong learning, intergenerational solidarity and positive youth
      development: the case of Hong Kong.
AB  - Elder lifelong learning has been promoted worldwide under different modes for
      upgrading quality of life of elders and actualizing successful aging. With
      multiple objectives, some modes of the elder lifelong learning program attempt to
      simultaneously address the social issues of age-segregation and negative
      perceptions of older people by adopting an intergenerational approach. Such an
      approach links the two non-biological generations--the young and the old-
      together purposefully for nurturing intergenerational solidarity and integration.
      Although program evaluation studies demonstrate the positive impacts and effects
      of an intergenerational approach on older people, its impact on young people is
      not well-researched. This paper explores intergenerational solidarity generated
      from the intergenerational-mode elder lifelong learning program in Hong Kong and
      argues how it contributes to positive youth development.

PMID- 21870670
TI  - A methodological critique of parenting research in Hong Kong.
AB  - This paper attempts to examine methodological issues pertinent to parenting
      research in Hong Kong. Using 90 studies indexed in the PsycINFO database, eight
      methodological limitations of parenting research in Hong Kong are highlighted.
      The limitations include over-reliance on non-locally validated translated
      measurements, lack of longitudinal studies, infrequent utilization of
      perspectives based on multiple informants, lack of usage of multiple indicators
      of different parenting processes, infrequent use of advanced statistical data
      analysis methods, underuse of linear mixed method analyses, predominance of
      convenience sampling, and lack of qualitative studies. Future research directions
      with reference to these methodological limitations are discussed.

PMID- 21870671
TI  - A conceptual critique of parenting research in Hong Kong.
AB  - Parenting processes have been investigated for over 30 years in Hong Kong. Three
      conceptual limitations are identified, based on 90 studies selected from the
      PsycINFO database: lack of investigation of indigenous parenting concepts; lack
      of investigation of causes, concomitants and consequences of the parenting
      process; and lack of alternative explanations for results. Suggestions for
      improvement are also made in each area. Limitations of the present study are
      discussed.

PMID- 21870672
TI  - Poverty and adolescent developmental outcomes: a critical review.
AB  - This paper reviews the impact of poverty on adolescent developmental outcomes.
      Based on a review of the literature, the impact of poverty on the psychological
      development of adolescents, the pathways through which poverty operates, and the
      protective factors of adolescents from the impact of poverty are outlined. The
      review showed conceptual problems in the literature, including the neglect of
      attention paid to cultural diversity and intervening processes between poverty
      and child developmental outcomes. This review also highlights methodological
      challenges, including the lack of longitudinal and qualitative studies in the
      field and the problems of using single informant perspective to study dynamic
      family processes. Recommendations for directions of future research are offered.

PMID- 21870673
TI  - Quantitative and qualitative approaches in the study of poverty and adolescent
      development: separation or integration?
AB  - This paper examines the use of quantitative and qualitative approaches to study
      the impact of economic disadvantage on family processes and adolescent
      development. Quantitative research has the merits of objectivity, good predictive
      and explanatory power, parsimony, precision and sophistication of analysis.
      Qualitative research, in contrast, provides a detailed, holistic, in-depth
      understanding of social reality and allows illumination of new insights. With the
      pragmatic considerations of methodological appropriateness, design flexibility,
      and situational responsiveness in responding to the research inquiry, a mixed
      methods approach could be a possibility of integrating quantitative and
      qualitative approaches and offers an alternative strategy to study the impact of
      economic disadvantage on family processes and adolescent development.

PMID- 21870674
TI  - Perceptions of older people among Chinese adolescents: conceptual and
      methodological issues.
AB  - Ageism against older people exists worldwide almost among all age groups and
      adolescents are of no exception. Numerous studies with specific reference to
      adolescents of different age, gender, educational level, socioeconomic
      background, knowledge about aging and experiences with older people showed that
      they had different perceptions of and attitudes toward older people, but such
      findings are not entirely conclusive. The situation of Hong Kong is even more
      confused as there are few studies examining this topic. It is argued that the
      conflicting findings are largely due to conceptual and methodological problems in
      the studies. This paper examines the conceptual and methodological issues in this
      area and outlines suggestions for future research.

PMID- 21870675
TI  - Applications of interpretive and constructionist research methods in adolescent
      research: philosophy, principles and examples.
AB  - This paper attempts to give a brief introduction to interpretivism,
      constructionism and constructivism. Similarities and differences between
      interpretivism and constructionism in terms of their histories and branches,
      ontological and epistemological stances, as well as research applications are
      highlighted. This review shows that whereas interpretivism can be viewed as a
      relatively mature orientation that contains various traditions, constructionism
      is a looser trend in adolescent research, and in the narrow sense denotes the
      "pure" relativist position, which refers to a discursive approach of theory and
      research. Both positions call for the importance of clearly identifying what type
      of knowledge and knowledge process the researcher is going to create, and
      correctly choosing methodology matching with the epistemological stance. Examples
      of adolescent research adopting interpretivist and constructionist orientations
      are presented.

PMID- 21870676
TI  - Fears about treatment among young drug abusers in Hong Kong.
AB  - This study examined fears about drug treatment among 300 young male heroin
      abusers in Hong Kong (172 newcomers and 128 repeaters) recruited from non
      government treatment agencies. An indigenous 35-item Fears about Treatment Scale
      (Fears Scale) was developed to measure fears about treatment among the
      participants. Results showed that four factors (fear of failure, fear of labeling
      or disclosure, fear of maladaptation and fear of withdrawal) were abstracted from
      the scale. Reliability analyses showed that subscales based on these four factors
      and the total scale were internally consistent. The findings showed that
      treatment failure was the major fear in the respondents. The present findings
      suggest that drug treatment and rehabilitation services should help clients,
      particularly young substance abusers, mitigate their treatment fears.

PMID- 21870677
TI  - Getting to hear the voices of the unwed mothers: their decisions to keep their
      babies for lone motherhood.
AB  - Drawing upon interview data from a study investigating the experiences of 20
      unwed mothers in Hong Kong, this article explores the narratives of the
      participants, especially their decisions in keeping their babies and to taking up
      the responsibilities of lone motherhood. Specific focus is given to the
      importance of their narratives so that their voices are heard - how they
      positioned themselves in relation to dominant cultural scripts surrounding lone
      motherhood. Their voices have relevance for helping professionals working with
      young people who play a useful role in facilitating and supporting unwed mothers
      within their locality, as well as for the general public who play an important
      role in "breaking" the labels and isolations of unwed mothers.

PMID- 21870678
TI  - Health reform spurs new physician models.

PMID- 21870679
TI  - Team up for better care.

PMID- 21870680
TI  - Institute cultivates long term care leadership skills.

PMID- 21870681
TI  - Culture & communication.

PMID- 21870682
TI  - The corner office.

PMID- 21870683
TI  - Radiology extenders revisited: to bill or not to bill.

PMID- 21870684
TI  - ICD-10: acute myocardial infarction.

PMID- 21870685
TI  - Revisit, revamp, and revitalize your business plan: part 3.
AB  - Managing with financial statements is discussed, including fundamental
      definitions and conventions related to this process such as an income statement
      and a balance sheet. Balanced scorecards and dashboards can be used to measure
      progress and to communicate achievements. Steps taken to defining data using
      KPIs, sourcing data, and structuring the scorecard are outlined. A core part of
      managing with financial statements is understanding how to drive the business and
      engage the staff using balanced scorecards.

PMID- 21870686
TI  - The journey from entitlement to performance redux.

PMID- 21870687
TI  - TRACE program: improving patient safety.
AB  - The Tools for Radiation Awareness and Community Education (TRACE) program was
      designed as a two phase approach to radiation dose awareness and overall patient
      dose reduction achieved through patient and community education, physician
      awareness, staff training, and technological enhancements. It was made possible
      by the AHRA and Toshiba Putting Patients First grant program. Phase one of the
      program began by engaging radiation safety committee and management to address
      new radiation safety policy and procedures followed by patient and community
      education. Next, fluoroscopy dose reduction was addressed through physician
      awareness and dose notification. The final step was CT dose reduction through
      protocol changes. Phase two will contain three components: The implementation of
      software that will assist in recording and reporting dose; patient and referring
      physician notification for radiation dose >3 Gy; and CT dose reduction through
      technology and additional changes to protocols.

PMID- 21870688
TI  - Four rules to service.
AB  - Hospitals weighing the benefits of a busy and pleased cardiologist, neurologist,
      oncologist, or surgeon against the happiness of the radiologists will result in
      the radiologists drawing the short straw. Radiologists are seen as contracted
      physicians who do not refer patients. As an outpatient imaging center, it is very
      important to collaborate with your radiologists to keep your facility from
      becoming a commodity. Collaborating with your radiologists and working together
      to drive outcomes, not statistics, will allow others to see a defined value for
      your service. Each physician office will have unique preferences for the imaging
      needs of their patients. Imaging services can no longer take the "one size fits
      all" approach with referring physicians or patients. Individualized scheduling
      process for a specific office will help them find the needed value for your
      services. Service is only one small, but important way, to provide a qualitative
      differentiation across your market.

PMID- 21870689
TI  - Referring physicians' perceived benefits of PACS: a regional survey pre- and post
      PACS implementation.
AB  - Referring physicians in theWestern Health Authority of Newfoundland and Labrador
      were administered a survey before and after PACS was implemented across all acute
      sites in the province.The survey had 31.7% and 35.0% response rates,
      respectively. There was considerable support found for PACS both pre- and post
      implementation in the areas of exam access and review, PACS functionality,
      quality of reports, efficiency, and site-to-site professional consultations.There
      was limited support that PACS reduced hospital length of stay. Surveys such as
      the one employed in this study provide an opportunity to measure the perceived
      benefit and challenges of PACS in a relatively cost effective manner.

PMID- 21870690
TI  - Managing distress, discomfort, and anxiety in imaging.
AB  - Positive patient interactions and experiences not only help the customer but also
      directly affect the bottom line. Waste of overhead can be limited by simply
      changing the way staff talks with patients. It is important to include rapid
      rapport skills and ways to positively shape the patients' experience right from
      the start instead of waiting and possibly having a procedure or scan disrupted.
      It "takes a village" to have a smooth transition in how communication is used
      throughout the department. A method of patient interaction called Comfort Talk
      was developed in which schedulers, receptionists, nurses, technologists, and
      physicians are extensively trained in advanced rapport skills and setting
      expectations.

PMID- 21870691
TI  - A culture of extraordinary care: part 3.

PMID- 21870692
TI  - Take things one day at a time.

PMID- 21870693
TI  - Proactive defense.
AB  - Make sure your hospital adheres to HITECH's privacy and security rules to avoid a
      compliance review.

PMID- 21870694
TI  - Quality care for all.
AB  - Research shows that minority populations don't fare as well on many health status
      factors. Digging into the demographic and quality data at your hospital will
      reveal where to focus efforts.

PMID- 21870695
TI  - Crisis management and maintaining the public trust.

PMID- 21870696
TI  - Models of transformation.
AB  - Reform's ramifications are still in flux, but many hospitals already have
      revamped operations. The hospitals profiled have adopted new payment schemes and
      optimized services.

PMID- 21870697
TI  - Keys to lasting partnerships.
AB  - Physician alignment will be essential to success under value-based care. Learn
      the six steps to building long-term, effective integration.

PMID- 21870698
TI  - Population health delivers.
AB  - Trustees must drive the decision to embrace population health.

PMID- 21870699
TI  - A push for clinical integration.
AB  - Clinical integration is the only way to improve quality and manage costs.

PMID- 21870700
TI  - Information technology.
AB  - An annual technology assessment identifies board influence and rich data
      collection.

PMID- 21870701
TI  - [The practical value of breast cancer molecular classification].
AB  - Breast cancer is the most common female cancer in the Western World and the
      leading cause of cancer death among women. It is a clinically heterogeneous
      clinical entity. Histologically similar tumors may have different prognosis and
      may respond to therapy differently. It is believed that these divergences in
      clinical behavior are due to molecular differences between microscopically
      similarneoplasmas. Breast cancer is a complex disease of genetic background
      characterized by accumulation of molecular alterations resulting in an important
      clinical heterogeneity. Current prognostic factors (including lymph node status,
      tumor size, histological grade, hormone receptor status, ERBB2 expression and
      patient age) are insufficient to predict accurately the clinical outcome.
      Microarray expression profiling classifies breast cancer into five (or six)
      molecular subtypes: luminal A, luminal B, basal-like, HER2 and normal breast-like
      (sometime luminal C, too). The different molecular classes of breast cancer not
      only have different prognoses but also show distinct sensitivities to
      preoperative chemotherapy. They have specific clinical profiles, as well
      (reproductive factors, age and race). It means that new, modified prevention
      strategy for breast cancer is necessary.

PMID- 21870702
TI  - [Evaluation of clinical usefulness of selected laboratory markers in the
      prediction of myocardial infarction in patients under secondary prevention].
AB  - The aim of the study was to evaluate the range of chronic inflammation in
      patients after second or subsequent myocardial infarction, and to compare it with
      its range in patients after first MI. MATERIAL AND METHODS: C-reactive protein
      measurement clinical value was examined by high sensitivity CRP method (hsCRP)
      and compared to clinical value of other heart attack risk factors: total
      cholesterol (TC) and cholesterol in HDL fraction (HDL-C), triglycerides (TG) and
      fibrinogen (FBG). The research included 120 patients in two investigated groups:
      Z2--30 patients undergoing secondary prevention after second (subsequent) heart
      attack, and Z1--30 patients with first myocardial infarction. There were two
      reference groups: KOR--30 people undergoing planned coronarography and K--30
      healthy individuals. Groups Z2, Z1 and KOR patients were treated with PCI
      (percutaneous coronary intervention). RESULTS: HsCRP medians for group Z2 (2.65
      mg/I) and groups Z, (2.25 mg/) and KOR (2.35 mg/l) were significantly higher than
      in group K (1.10 mg/dl). CONCLUSIONS: Highest clinical value of hsCRP in coronary
      attack prediction was confirmed. Relative area under ROC curve (AUC) was highest
      in group 2, higher than in group Z1 (0.778 and 0.711, respectively). In patients
      undergoing secondary prevention, group Z2, hsCRP measurement showed higher
      clinical value in subsequ ent myocardial infarction prediction than in first one.
      In groups Z2 and Z1, HDL-C measurement also shows high diagnostic value for
      coronary risk assessment. AUC are 0.875 and 0.782, respectively. However, in
      treatment with statins, high AUC values do not necessarily reflect myocardial
      infarction risk.

PMID- 21870703
TI  - [Application of activated eptacog alfa in cardiac surgery].
AB  - Severe bleeding in cardiac surgery is often difficult to treatment. Antybleeding
      drugs often are out of order. The aim of the study was to assess the efficacy of
      activated eptacog alfa treatment of patients with massive postoperative bleeding,
      which can not be controlled with conventional therapy MATERIAL AND METHODS:
      Activated eptacog alfa was used in 18 patients after cardiac surgery. The
      patients had normal results of coagulation screening prior to surgery. We
      evaluated the average blood loss prior to and after administration of activated
      eptacog alfa. The average dose was 30.95 mcg/kg following administration of drugs
      antybleeding, transfusion KKCz, FFP, cryoprecipitate, PLT was decided to include
      the treatment of activated eptacog alfa. RESULTS: At a dose of 30.95 mcg/kg,
      bleeding stopped in 12 patients. 6 patients required reoperation because of
      persistent bleeding. CONCLUSIONS: Administration of activated eptacog alfa
      clearly limits the amount of transfused blood products. Activated eptacog alfa
      improves outcomes in patients with intractable postoperative bleeding cardiac
      surgery. Stops bleeding in patients who received preoperative clopidogrel. 1
      patient required reoperation after administration of activated eptacog alfa.

PMID- 21870704
TI  - [Leptin receptor polymorphism--the evaluation of the hetero- and homozygote
      frequencies in population of children suffering from acute lymphoblastic leukemia
      (ALL) and healthy children].
AB  - Leptin, together with its specific receptor, plays a significant role in various
      metabolic and biochemical processes in a human body. The Q223R polymorphism of
      the leptin receptor gene is associated with the increased risk of developing
      metabolic syndrome. Body exhausting treatment administered to children suffering
      from ALL, combined with potentially disadvantageous polymorphism, may lead to
      developing obesity, diabetes and high blood pressure, all of which constitute the
      metabolic syndrome factors. The aim of the study was to evaluate the hetero- and
      homozygote frequencies for the Q223R polymorphism of the leptin receptor gene in
      the examined group of Caucasian children and adolescents suffering from ALL,
      compared to the control group. MATERIAL AND METHODS: 95 children underwent
      genetic testing (52 children in the examined group, with 43 children in the
      control group), all of them being treated in Department of Pediatric Oncology and
      Hematology Medical University of Bialystok. The examined group consisted of 31
      boys and 21 girls, with 30 and 13 subjects in the control group, respectively.
      The division into heterozygotes and homozygotes of the leptin receptor gene
      polymorphism was established by the RFLPmethod (restrictedfragmentlength
      polymorphism), using the polymerase chain reaction (PCR). Products obtained from
      that reaction were splitted by means of 4% agarose gel electrophoresis. To
      determine the importance of differencies between the frequency of alleles and the
      frequency of genotypes for the set groups, a software--DE-FINETTI DIAGRAM and
      Hardy-Weinberg test was used, p < 0.05 is concluded to be a statistically
      significant result. RESULTS: In the examined group there were observed slightly
      higher frequencies of heterozygous individuals with the AG genotype (50%),
      compared to GG genotype (28.8%) and AA genotype (21.2%). In the control group the
      genotype distribution was as follows: AG genotype --48.8%, GG genotype--39.5% and
      AA individuals--11.6%. No significant differences were observed between the set
      groups in question. CONCLUSIONS: The heterozygote and homozygote frequencies for
      the Q223R polymorphism of the leptin receptor gene examined in the group of
      children suffering from ALL do not differ from the frequencies examined in the
      population of healthy children.

PMID- 21870705
TI  - [Evaluation of beta2-microglobuline expression level in gastrointestinal tract
      tumors due to usefulness as a reference gene in PCR method].
AB  - Quantitative and semi-quantitative determination of gene expression by PCR plays
      an important role in studying of tumors initiation and progression mechanisms.
      Selection of appropriate reference gene is a critical factor influencing the
      results of gene expression analysis. One of the most commonly used reference
      genes in PCR is beta2-microglobuline (beta2-M). Recent studies showed however
      that expression of some common reference genes might be unstable, therefore it is
      necessary to verify again their usefulness. The aim of the study was to determine
      the level of beta2-M mRNA in normal and tumor tissues of gastrointestinal tract
      due to adequate selection of reference gene in gene expression studies. MATERIAL
      AND METHODS: Samples were taken from 253 patients operated on for
      gastrointestinal tract tumors: 22 with oral cavity cancer, 12 with benign and 50
      with malignant liver tumors, 86 with colorectal cancer, and 83 with metachronous
      metastases to liver. Also 56 patients with liver cirrhosis were studied, which
      was treated as pre-tumor state. Together 309 patients were studied. RNA was
      isolated from tissues by Chomczynski method. The expression level of 12-M was
      determined by reverse transcriptase PCR (RT-PCR) and given in terms of optical
      density values. RESULTS: Expression of beta2-M was observed in all studied
      tissues. There were no differences between normal and tumor tissue. The level of
      expression of beta2-M was different due to type of studied tissue (oral cavity,
      liver, colon). CONCLUSIONS: The lack of significant differences in beta2-M
      expression level in normal and tumor tissues indicated that beta2-M can be used
      as reference gene in studies of gene expression in gastrointestinal tract tumors.
      On the other hand differences of beta2-M expression level in different types of
      tissues point to its tissue specificity and suggest application in PCR of more
      than one reference gene.

PMID- 21870706
TI  - [Utility of clinical differentiation and microbiological examination for
      appropriate antibiotic therapy of acute pharyngotonsillitis in children].
AB  - The differentiation between streptococcal pharyngotonsillitis and that of viral
      etiology is crucial, since it allows to discriminate patients who need to be
      treated with the use of antibiotics from those who only need symptomatic
      treatment. For that purpose, Centor/Mclssac's scale, based on the clinical
      examination and a history of a patient, is suggested by "Polish Recommendations
      for the diagnosis and treatment of community-acquired respiratory tract
      infections 2010". In patients who have obtained two or more points according to
      this scale, a definitive diagnosis of streptococcal pharyngotonsillitis depends
      on the identification of the bacterium, which can be performed by throat swab
      culture or by rapid antigen detection test. The aim of the study was to evaluate
      utility of clinical differentiation, rapid antigen detection test and throat swab
      culture for appropriate antibiotic therapy of acute pharyngotonsillitis in
      children. To the best of our knowledge, this is the first survey of this type
      carried out in Poland. MATERIAL AND METHODS: 42 children in the age of 3-14 years
      with acute pharyngotonsillitis who obtained at least two points in Centor/
      Mclssac's scale took part in our study. Two throat swabs were obtained from every
      child, one of them was used to perform rapid test, and the second one was
      cultured on Columbia blood agar. Grey-white colonies with beta-hemolysis were
      classified to the groups A, B, C, D, F and G according to Lancefield with the use
      of bacitracin discs and latex agglutination test. RESULTS: 50% of children
      obtained 4 points and 40.5% of them received 5 points in Centor/Mclssac's scale.
      QuickView+ Strep A test turned up to be consistent with culture in 97.6% of
      cases. On the grounds of rapid test and culture results patients were subdivided
      into 3 groups: I--infected with S. pyogenes (50.0%), II--infected with other
      groups of beta-hemolytic streptococci (9.5%), III--infected with viruses (40.5%).
      CONCLUSIONS: It is impossible to recognize streptococcal pharyngitis only on
      clinical grounds, the diagnosis must be confirmed by laboratory methods. In
      children with high risk of streptococcal pharyngitis QuickView+Strep A test
      possesses diagnostic value comparable to culture in the detection of S. pyogenes,
      however negative rapid test results in such patients should be confirmed by
      culture. Antibiotic therapy should be initiated on the base of microbiological
      examination.

PMID- 21870707
TI  - [The usefulness of high frequency ultrasonography in dermatological practice-
      ultrasound features of selected cutaneous lesions].
AB  - Typical diagnostic process in dermatology includes clinical assessment,
      dermoscopic and histopathologic examination. Microsonography was initiated in
      seventies and much progress in the development of high-frequency scanners
      occurred since that time. The aim of the study was the assessment of high
      frequency ultrasonography in dermatologic diagnostics. MATERIAL AND METHODS:
      Examination was performed with 30 MHz ultrasound transducer with 0,1 mm
      resolution and 7 mm penetration. We examined patients with benign and malignant
      neoplasms, cicatrical alopecia and morphea. RESULTS: Sonographically, the normal
      skin is composed of three layers: an epidermal entry echo, dermis and
      subcutaneous tissue. In healthy skin we can image small hypoechoic areas which
      correspond to hair folicules, vessels and sebaceous glands. Most of small skin
      neoplasmatic lesions were hypoechogenic and homogeneous on examination. Extensive
      lesions were multicomponent with normo-, hypo- and anechogenic structures. The
      assessment of lesion's boarders allows sometimes to conclude the invasiveness of
      the lesion. Areas of skin with clinically visible atrophy showed diffuse
      increasing of echogenicity. In early lesions, without accomplished fibrosis,
      diffuse decreasing of echogenicity can be observed, that is probably caused by
      inflammatory infiltration. In comparison to the healthy skin, the ultrasound scan
      of sclerotic skin shows a wide entry echo and highly reflective, thicker dermis
      as a result of the collagen fibers accumulation. CONCLUSIONS: Above data suggest
      that ultrasonographic examination may be a valuable dermatologic diagnostic tool
      that completes classical dermatologic diagnostics and helps to plan the
      treatment.

PMID- 21870708
TI  - [Auditory-verbal learning test by Luria in the examination of psychiatric
      patients].
AB  - The aim of the study was an evaluation of memory process course efficacy in
      healthy subjects (n = 37), patients with schizophrenia (n = 44), patients with
      depressive disorders (n = 58) and patients with organic mood disorder (n = 33).
      MATERIAL AND METHODS: A sample of 172 persons aged 18-55 years participated in
      the study. Cognitive functions were evaluated by the auditory-verbal learning
      test by Luria (AVLT). RESULTS: The best results in the first trail (M = 5,84, SD
      = 1,38) and after 30 minutes (M = 8,92, SD = 1,23), were obtained by healthy
      subjects, while the lowest scores were noted for the subjects with organic mood
      disorder (M = 4,67, SD = 1,24 and M = 5,85, SD = 2,56). Patients suffering from
      depressive disorders: M = 5,01 (SD = 1,39) and M = 6,68, (SD = 2,21). Patients
      suffering from schizophrenia: M = 4,84 (SD = 1,52) and M = 6,18 (SD = 2,16).
      Relevant statistical differences among healthy subjects and mentally ill patients
      and lack of any relevant differences among mentally ill patients were observed.
      Sten norms of AVTL were developed for general population. CONCLUSIONS: Healthy
      subject achieved higher results in AVLT than patients suffering from
      schizophrenia, depressive disorders and organic mood disorders. Any relevant
      differences among mentally ill patients were observed. Sten norms of AVTL were
      developed for general population.

PMID- 21870709
TI  - [Excision of the rectum due to carcinoma in patient with hereditary hemorrhagic
      teleangiectasia].
AB  - Hereditary hemorrhagic telangiectasia (HHT) also known as Rendu-Osler-Weber
      disease, is a rare, autosomal dominant disorder of the fibrovascular tissue.
      Clinically, it is characterized by the triad of symptoms of mucocutaneous
      telangiectasias and arteriovenous malformations of visceral organs, recurrent
      hemorrhages from vascular changes at different localization, and familial
      occurrence. A coexistence of HHT syndrome and malignant neoplasms in various
      sites, including large bowel, is suggested. The authors describe the case of 67
      year old woman with HHT with massive bleeding from digestive tract in history and
      persistent chronic sideropenic anemia. In upper gastrointestinal endoscopy
      performed in regional hospital multiple telangiectasias in the stomach were
      found. These were diagnosed as the possible bleeding source therefore colonoscopy
      was not performed. After twelve months in diagnostic colonoscopy due to chronic
      anemia carried out in our Institute, rectal carcinoma was found. The patient were
      subjected to surgery--lower anterior excision of the rectum. Intra operatively
      and in the postoperative period complications were not observed. CONCLUSION: In
      every case of bleeding from digestive tract and also in chronic anemia in
      patients suffering from Rendu-Osler-Weber disease, beside the endoscopy of
      esophagus, stomach and duodenum, full visualization of the large bowel is
      necessary to exclude malignant neoplasm. In the presented case no colonoscopy
      performed in the regional hospital delayed the carcinoma diagnosis by twelve
      months.

PMID- 21870710
TI  - [Impact of L-thyroxine replacement therapy on pituitary changes secondary to
      congenital primary hypothyroidism--three cases report].
AB  - The aim of the study was an evaluation of the impact of L-thyroxine substitution
      therapy on the size and structure of the pituitary gland using MRI in three
      patients with pituitary hyperplasia or tumor secondary to primary congenital
      hypothyroidism. Along with imaging studies (MRI, skull X-rays) all patients had
      performed hormonal tests. All hormones (except adrenocorticotropic hormone) of
      anterior pituitary lobe were measured in basal condition, and some of them (GH,
      PRL) after stimulation tests, which showed hyperprolactinemia in one case and
      pituitary somatotropin insufficiency in the other. Only in one out of three
      patients the regression of the pituitary enlargement was complete, whereas in
      second case the regression was partial and in third patient evaluation revealed
      no changes on the MRI. Correct L-thyroxine therapy prevents enlargement of
      pituitary gland and may regress these changes, but is not the only outcome of
      pituitary enlargement. Those results shows, that other coexisting disturbances
      like TSH-secreting adenoma or thyroid hormone resistance must be considered when
      the treatment is not successful.

PMID- 21870711
TI  - [The damage of the ulnar nerve on the level Guyon's canal--four cases report].
AB  - The damage of the ulnar nerve on a level Guyon's canal is a rare occur in
      clinical practice. The presence of pathology mass, injury or long-lasting
      pressure the most often be caused. The authors represent four patients from this
      syndrome, in three cases the damage the long-lasting pressure of nerve was caused
      in neighborhood Guyon's canal, and in one injury of neighborhood of wrist. In
      therapeutic-rehabilitation management was recommended the avoidance the loading
      of adjacent of wrist. In two cases in catamnestic examination after retreat
      provocative factor, the symptoms of damage of ulnar nerve revealed. The
      principles of diagnosis and treatment in adjacent of wrist the damages of ulnar
      nerve in article were presented.

PMID- 21870712
TI  - [Trans-fatty acids--effects on coronary heart disease].
AB  - Trans-fatty acids (TFA) are formed during the industrial process of hydrogenation
      of vegetable oils. The consumption of hydrogenated fats has increased
      significantly over the last few decades. In Poland, the average daily intake of
      TFA for adults was estimated to be 2.8 to 6.9 g; which greatly exceeds the
      recommended daily maximum of 2 g/day (less than 1% of total energy intake).
      Increasing trans-fatty acid intake has detrimental effects on the lipid profile:
      TFA raise total cholesterol, LDL-cholesterol and triglyceride concentrations, and
      decrease HDL-cholesterol levels. Moreover, dietary trans-fatty acids may increase
      plasma levels of lipoprotein (a) and biomarkers of inflammation and endothelial
      dysfunction. Several studies have demonstrated that a high intake of TFA is
      associated with an increased risk of coronary heart disease. In addition, TFA
      consumption has been implicated as an independent risk factor for sudden cardiac
      arrest. It is therefore necessary to reduce the intake of hydrogenated fats rich
      in trans-fatty acids in order to minimize the adverse effects of TFA on health.

PMID- 21870713
TI  - [The alteration of proteins glycosylation in liver diseases].
AB  - The changes in protein glycosylation play an important role in the pathogenesis
      and progression of various liver diseases. In the different types of liver
      diseases the same type of alterations seems to reappear. They are:
      hyperfucosylation, increased branching and the presence of increased bisecting N
      acetylglucosamine of glycans. For these modification are responsible the
      activities of different glycosyltransferases, that are generally increased in
      liver diseases. However, the changes in the glycans structure of serum proteins
      are characteristic in the liver diseases of different etiologies and therefore
      could be potentially used in the diagnostics of liver pathology

PMID- 21870714
TI  - [The effects of antidepressants on sleep in depressed patients with particular
      reference to trazodone in comparison to agomelatine, amitriptyline, doxepin,
      mianserine and mirtazapine].
AB  - Disturbed sleep is a core symptom of depression and is among diagnostic criteria
      for depressive episode. Effects of an antidepressant drug on sleep are important
      for its clinical profile. Rapid improvement of sleep quality is particularly
      indicated in depressed patients with insomnia, anxiety, agitation and suicidal
      thoughts. The aim of the study was to evaluate the effects of trazodone on sleep
      in depressed patients in comparison to other sleep promoting antidepressants:
      agomelatine, amitriptyline, doxepin, mianserine and mirtazapine according to
      analysis of scientific publications. Sedative antidepressants including trazodone
      are regarded as treatment of choice in depression with agitation, anxiety or
      insomnia. They are also frequently used in low dose to promote sleep, as an
      alternative to hypnotics. Such approach to treatment of insomnia in depressed
      patients protects them against dependence on hypnotic drugs. Additionally, the
      antagonistic action of antidepressants on serotonergic 5-HT2 receptors improves
      not only the sleep continuity, but promotes also slow wave sleep. Trazodone and
      mirtazapine in comparison to many other antidepressants do not suppress REM
      sleep. Antidepressants have different effects on sleep. In treatment of
      depression sedative antidepressants should be administered in the full,
      recommended dose. However, if they are administered as concomitant treatment only
      to promote sleep, low doses are indicated. Too late administration time and too
      high dose are the most common factors related to failure of insomnia treatment
      with these drugs.

PMID- 21870715
TI  - [Culturomics--a new direction for scientific research, developed at Harvard
      University].

PMID- 21870716
TI  - [Chronic hepatitis C, steatosis and insulin resistance--clinical implications].
AB  - Chronic infection with hepatitis C virus is nowadays responsible for many cases
      of liver disease. According to recent research, it seems to be characterized by a
      great deal of metabolic abnormalities, most of them due to insulin resistance,
      which is present in the virus C-induced disease more often than in chronic
      hepatitis B or in the general population. As insulin resistance significantly
      impairs the natural course of the viral disease by reducing the efficacy of
      antiviral treatment and aggravating the development of fibrosis, it becomes more
      and more plausible that therapeutic intervention aiming to reduce it might
      contribute to a better course in many patients. Hepatic steatosis is also a
      frequent feature of chronic hepatitis C, being either induced by the infection
      with genotype 3 or by a predisposing metabolic background. The relation between
      steatosis and viral disease prognosis is controversial, probably due to the
      various factors inducing lipid accumulation. A better understanding of the
      metabolic substrate of chronic hepatitis C would help developing new approaches
      in its diagnosis and therapy, hopefully providing a better future to many
      patients.

PMID- 21870717
TI  - [Upper-extremity deep vein thrombosis: current concepts in diagnosis and
      treatment].
AB  - Upper-extremity deep vein thrombosis is a rare manifestation of venous
      thromboembolic disease. In the past few decades, the clinical importance of upper
      extremity deep vein thrombosis has increased because of the wider use of central
      venous catheters and the development of ultrasonography as a simple and accurate
      objective diagnostic method. Primary upper-extremity deep vein thrombosis is a
      rare disorder (2 per 100,000 persons per year), which comprises (1) Paget
      Schroetter Syndrome, also known as effort thrombosis, and (2) idiopathic upper
      extremity deep vein thrombosis. Secundary upper-extremity deep vein thrombosis
      develops in patients with upper extremity central venous catheters, pacemakers or
      cancer and accounts for most cases of upper-extremity deep vein thrombosis. The
      imaging modes used for diagnosis are: duplex ultrasound, magnetic resonance.
      Contrast venogram is the standard diagnostic test for characterization of the
      anatomy. A staged, multimodal approach to Paget-Schroetter Syndrome can
      effectively restore venous patency, reduce the risk of rethrombosis, and return
      the patient to normal function. Primary care physicians should be aware of this
      condition and its atypical presentations, because delayed recognition in a high
      functioning persons can be potentially disabling.

PMID- 21870718
TI  - [Prevalence of chronic hepatitis B virus (HBV) infection in closed communities
      and risk behaviour].
AB  - AIM: To determine the prevalence of chronic hepatitis B virus infection in closed
      communities and the relations between the risk behavior and VHB infection.
      MATERIAL AND METHODS: In this study we included persons deprived of personal
      freedom at Bacau Correctional Facility. The subjects filled out a questionnaire,
      which contained identification and epidemiologic data (detention history,
      evaluation of the risk factors), as well as an informed consent. All subjects
      were tested for HBsAg. RESULTS: According to the performed tests, the general
      prevalence of hepatitis B and C in this correctional facility was 15.34%, with a
      prevalence of hepatitis B of 10.74%. Although these figures show a higher
      prevalence in this population than within the general population, they are lower
      than the figures reported in correctional facilities from other countries.
      CONCLUSIONS: The results confirm the fact that the population in correctional
      facilities is at high risk for hepatitis B infection, the ways of disease
      transmission being already known (infected blood, injected drugs, tattooing,
      homosexual relationships).

PMID- 21870719
TI  - [Depression and cardiovascular diseases in the elderly].
AB  - The aim of this study was to reveal if there are connections between depression
      and cardiovascular disease. MATERIAL AND METHOD: We have studied 413 patients
      from Jorasti, Jud Galati on a two-years period (2008-2010). On these patients
      there was performed a careful history taking and they were physically examined
      (height, weight, body mass index, waist, blood pressure, heart rate). There was
      also performed an ECG (electrocardiogram), there were measured the levels of
      cholesterolemia, HDL-cholesterolemia, trygliceridemia and creatininemia. We used
      the Geriatric Depression Scale (GDS) in order to evaluate depression. RESULTS: in
      these patients there was noticed a higher prevalence of dyslipidemias, obesity
      and depression in women. Out of the 46 women with mild and severe depression 32
      are overweight, 7 have obesity, 29 a high cholesterol, 23 a high LDL-cholesterol;
      all of them had a high risk or the presence of cardiovascular disease.
      CONCLUSIONS: Depression is an independent risk factor for producing a
      cardiovascular event; the level of cholesterol and of the blood preessure was
      higher in patients with severe depression, proving that the level of the
      cardiovascular risk factors increased with the severity of the depression.
      Treating the elderly, which often associate depression, makes necessary a careful
      evaluation of all comorbidities and risks, in order to establish perfect
      individualized strategies of improving the quality of life.

PMID- 21870720
TI  - Self-neglect in the case of the elderly. Where are we now?
AB  - Self-neglect in an elderly person is a behavior that threatens his/her own health
      and safety. It is present when a person refuses to adequately feed, water,
      shelter, or clothe himself, refuses medication or medical care, and personal
      safety measures. MATERIAL AND METHOD: This is a multicentric study of self
      neglect in three geriatric units from Finland, Greece and Romania The medical,
      social, psychological and behavioral profile analysis was based on a
      questionnaire; this questionnaire relied on existing studies and social, economic
      and medical facts in the three countries. The cognitive function, nutritional
      status, and the presence or absence of depression have also been assessed.
      RESULTS AND DISCUSSIONS: The data obtained until now support the importance of
      self-neglect among the elderly. The social-medical network should not only
      identify, diagnose, prevent, and treat the elderly affected by the phenomenon of
      self-neglect, but also educate the society to help them and, moreover, to prevent
      their marginalization.

PMID- 21870721
TI  - [Pierre Marie-Sainton cleidocranial dysplasia].
AB  - The paper presents a family with hereditary transmitted Marie-Sainton dysplasia
      affecting the father and his both children. This is a rare syndrome presenting an
      autosomal pattern of inheritance, characterized by a generalized defect in both
      membranous and endochondral bone formation resulting in clavicular aplasia,
      delayed ossification of the fontanelles and the sutures of the skull and
      prolonged retention of deciduous dentition with delayed eruption of the permanent
      teeth. The diagnosis is suggested by more or less complete clinical picture and
      confirmed by multiple radiological explorations (skull, thorax, spinal column,
      pelvis) and genetical examination. The genetic mutation for cleidocranial
      dysplasia (CCD) is found on chromosome six and is called CBFA1 (short for core
      biding factor al or RUNX2) and is the only gene known to be associated with CCD.
      The normal version of CBFA1 acts to induce osteoblasts which are the type of
      cells that lay down bone. Although associated psychosocial disorders can occur,
      the prognosis and life expectancy of this condition are favorable being
      conditioned however by the complexity of orthodontic procedures which are
      determinant for these patients life quality.

PMID- 21870722
TI  - [Experimental research on the influence of stress factors in an animal model of
      hypertension].
AB  - AIM: to investigate the influence of some stress factors in endothelin-1-induced
      hypertension. MATERIAL AND METHODS: The experiment was carried out on Wistar
      rats, treated intraperitoneally, for 4 weeks, as follows: Group 1: saline
      solution (0.5 ml/100 g weight); Group 2: saline solution + stress; Group 3:
      Endotelin-1; Group 4: Endotelin-l + stress; Group 5: Endotelin-1 + cholesterol
      diet (0.2 g/kbw/day); Group 6: Endotelin-1 + cholesterol diet + stress. Endotelin
      1 0.25 nmol/kbw was initially administered, followed by 0.5 nmol/kbw 15 min
      later, 2 times/week. Stress-inducing factors were immobilization and water
      immersion. In the 28th day of the experiment blood pressure was measured and
      blood samples were taken from the retro-orbitary plexus to assess plasma
      cortisol, blood count, phagocytic capacity of peripheral neutrophils, and serum
      complement activity. RESULTS AND DISCUSSIONS: Repeated administration of
      endotelin-1 determined an increase in blood pressure, statistically significant
      in stress conditions comparing to non-stressed animals. Our study proved a
      decrease of plasma cortisol, total leukocyte count, phagocytic capacity of
      peripheral neutrophils, without significant alterations in serum complement
      activity. CONCLUSIONS: Chronic exposure to complex stress conditions in rats with
      endothelin-1-induced hypertension determined a decrease of plasma cortisol
      levels, effect correlated with elevated blood pressure and decrease in the number
      and phagocytic function of peripheral neutrophils.

PMID- 21870723
TI  - RANKL/RANK/OPG molecular complex--control factors in bone remodeling in psoriatic
      arthritis.
AB  - AIM: To investigate the blood levels of bone remodeling factors (RANKL, OPG and
      Bone-ALP) in psoriatic arthritis patients. MATERIAL AND METHODS: Included in this
      study were 27 patients with psoriatic arthritis (CASPAR classification criteria)
      and 20 healthy subjects. The RANKL , OPG and Bone-ALP levels have been quantified
      by ELISA method. RESULTS: Peripheral blood concentrations were higher in
      psoriatic arthritis than in the healthy subjects, and a strong negative
      correlation between RANKL and OPG and between RANKL and Bone-ALP was also found.
      CONCLUSIONS: The increase in OPG and Bone-ALP serum level is strongly related to
      the increase in RANKL serum level in patients with psoriatic arthritis. The
      increase in OPG and Bone-ALP serum level induces the production of bone matrix
      parallel to the bone destruction mediated by RANKL. The follow up of the patients
      with psoriatic arthritis by early RANKL, OPG and Bone-ALP serum level
      determinations, and of bone metabolism markers (with specific role in bone
      remodeling), allows an accurate evaluation of disease activity and, in the
      future, could be a criterion for the initiation of specific, targeted treatment.

PMID- 21870724
TI  - [Neuroendocrine factors in hypertension during pregnancy].
AB  - Pregnancy induced hypertension is a condition of high blood pressure during early
      and mid-pregnancy. This type of hypertension is much like the chronic type, but
      it occurs only when the woman is pregnant and resolves completely after delivery.
      AIM: to evaluate some stress hormones in both normotensive and hypertensive
      pregnant women. MATERIAL AND METHODS: The study investigated the correlation
      between pregnancy induced hypertension and different immune/inflammatory and
      other markers. This exploratory investigation was performed on pregnant women
      diagnosed with pregnancy-induced hypertension, admitted to the lasi Cuza Voda
      Hospital. The psychometric assessment was performed by using the daily stress
      test, daily hassle scale, blood pressure measurements, and determination of
      anthropometrical parameters. Some parameters, such as the neuroendocrine and
      immune/inflammatory ones, and specific parameters for pregnancy hypertension were
      determined. RESULTS AND DISCUSSIONS: Our study revealed that blood pressure
      values presented significant differences between systolic, but not diastolic
      blood pressure values (p < 0.05). In 75% of subjects blood cortisol levels were
      not changed. Daily stress level assessment proved that low potential factors and
      an annoying environment had a high influence on both normotensive and
      hypertensive pregnant women. Hypertensive women also presented leukocytosis and
      thrombocytopenia. CONCLUSIONS: The research results showed that plasma cortisol
      level was higher in hypertensive pregnant women, compared with normotensives.

PMID- 21870725
TI  - Efficacy of Helicobacter pylori eradication therapy in cirrhotic patients with
      peptic ulcer disease.
AB  - Few studies have been focused on the role of Helicobacter pylori eradication in
      cirrhotic patients with peptic ulcer and the reported results are conflicting.
      AIM: To evaluate the efficacy of proton pump inhibitor (PPI)-based triple therapy
      on peptic ulcer course in patients with liver cirrhosis. MATERIAL AND METHODS:
      This prospective study was carried out in a tertiary-care hospital. Of the 63
      consecutive cirrhotic patients with peptic ulcer identified by endoscopy 39 (22
      males, 14 females, aged 53 to 62 years) entered the study. The patients with
      peptic ulcer and H. pylori infection received eradication therapy, while H.
      pylori negative patients received PPI treatment. H. pylori eradication was
      confirmed by rapid urease test and histological examination. Follow-up
      endoscopies were performed at 6 and 12 months. The patients with peptic ulcer
      recurrence were treated with PPI. RESULTS: Of the 39 selected patients 22 (56.4%)
      were H. pylori positive, and 17 (43.6%) were H. pylori negative. H. pylori was
      eradicated in 63.6% (14/22) of the patients. During the follow-up period 2 H.
      pylori negative patients died from variceal bleeding and hepatic encephalopathy,
      respectively, and one H. pylori positive patient did not return for further
      assessment). Ulcers recurring within 1 year were found in 14 of 36 (38.8%)
      patients. Peptic ulcer recurred in 4 of 21 (19.0%) H. pylori positive patients
      and in 10 of 15 (47.6%) H. pylori negative patients at study entry. Patients' age
      (p = 0.018), Child-Pugh stage (p = 0.019), peptic ulcer site (p = 0.008), and H.
      pylori negative status (p = 0.004) were significantly related to ulcer
      recurrence. CONCLUSIONS: Eradication of H. pylori infection in patients with
      liver cirrhosis and peptic ulcer disease could be helpful, but does not protect
      all cirrhotic patients from peptic ulcer recurrence. Most relapsed ulcers were
      gastric ulcers in H. pylori negative patients.

PMID- 21870726
TI  - [The role of capsule endoscopy in suspected Crohn's disease].
AB  - Capsule endoscopy (CE) revolutionized the small bowel examination. We emphasize
      the role of CE in suspected Crohn's disease, studying 24 investigations performed
      in the Institute of Gastroenterology and Hepatology. The global diagnostic yield
      was 54%, the specific diagnostic yield for Crohn's disease was 37.5%, the
      specificity was 100% and the retention rate was 4.1%. For maximum accuracy and
      efficiency, unitary administration and diagnostic criteria are needed, and for
      minimising the risk of complications, specific prior investigations would be
      suitable.

PMID- 21870727
TI  - [Therapeutic aspects of acute renal failure in children].
AB  - This article presents the results of a study on 20 children diagnosed with acute
      renal failure and treated with renal substitution methods at the Iasi IVth Clinic
      of Pediatric Nephrology in the interval 2003-2008. Treatment by intermittent
      hemodialysis IHD), peritoneal dialysis (DP), and continuous replacement-
      hemofiltering (HF) depends on the patient's features and unit resources. The
      advantages and limitations of every method of treatment are discussed. Future
      therapies for acute renal failure may find strategies for eliminating the
      inflammatory response.

PMID- 21870728
TI  - [Sensitization to ascaris lumbricoides and asthma severity in children].
AB  - There is little information concerning asthma severity and sensitization to
      Ascaris lumbricoides in pediatric patients. MATERIAL AND METHODS: The
      relationship between sensitization to Ascaris lumbricoides and asthma severity in
      219 patients with a high prevalence of parasitic exposure (IgE antibodies) was
      studied by using linear, multivariate and logistic regression. RESULTS:
      Sensitization to Ascaris lumbricoides was associated with positive skin tests for
      aeroallergens, increased total serum IgE, increased eosinophils, reductions in
      FEV1 and FEV1/FVC ratio, increased airway Methacholine, bronchodilator
      responsiveness, and hospitalizations for asthma in the past year. CONCLUSIONS:
      Sensitization to Ascaris lumbricoides is associated with increased severity of
      asthma among Romanian children. This association is mediated by a high degree of
      atopy among the asthma children sensitized to Ascaris lumbricoides and belonging
      to a population with a low prevalence of helminthiasis.

PMID- 21870729
TI  - Ectopic adrenocorticotropic hormone syndrome caused by a carcinoid tumor of the
      thymus. A case report.
AB  - Ectopic ACTH secretion accounts for less that 10% of all causes of endogenous
      Cushing's syndrome. Carcinoids are rare thymic tumors, and when associated with
      ACTH hypersecretion display local or distant aggressive behavior. A 32-year-old
      woman was admitted to the Endocrinology Unit for obesity, moon face, facial
      hirsutism, hyperpigmentation, and secondary amenorrhea. Laboratory test confirmed
      the hypercortisolism and excess ACTH, while dexamethasone suppressive test was
      negative. Thorax computed tomography (CT) showed an antero-superior mediastinal
      tumor invading the pericardium and left mediastinal pleura. A complete resection
      through median sternotomy of the tumor, pericardium and left mediastinal pleura
      was performed. After a one-year symptom-free period, hypercortisolism recurred,
      confirmed by laboratory findings. Although no signs of local recurrence were seen
      on thorax CT, left internal mammary lymph nodes involvement and vertebral body
      metastases at C7 and LI were found. Refractory electrolyte disturbances could not
      be corrected resulting in severe cardiac arrhythmia and death from cardiac
      arrest. The reported case draws attention on the aggressiveness of ACTH-secralso
      due to the refractory electrolyte disturbances with fatal outcome.

PMID- 21870730
TI  - [Myeloid metaplasia with myelofibrosis associated with acute coronary syndrome.
      Case report].
AB  - A 66-year-old man with myelofibrosis and myeloid metaplasia was admitted to
      hospital where he was diagnosed with acute coronary syndrome. Percutaneous
      transluminal coronary recanalization followed by drug-eluting stenting resulted
      in successful revascularization. Because besides thrombus formation the
      myeloproliferative syndrome has a potential for bleeding, it is very important to
      carefully follow-up any clotting abnormality.

PMID- 21870731
TI  - [Laparoscopic approach of the ovarian cyst tumors].
AB  - Given the continuous technical upgrade and increased surgical expertise,
      laparoscopy is replacing laparotomy in day-to-day gynecological surgical
      practice. Laparoscopic management offers many advantages for the patient:
      accurate diagnosis, minimal bleeding, reduced need for analgesia, less adhesion
      formation, fast recovery, better cosmetic results, shorter hospital stays (one
      day surgery in selected cases), and reduced costs for the patient and hospital.

PMID- 21870732
TI  - [Diagnostic and treatment algorithm for pharyngolaryngeal reflux].
AB  - Pharyngolaryngeal reflux (PLR) refers to backflow of stomach contents into the
      throat and larynx. Its diagnosis is difficult because of a variety of atypical
      symptoms, low sensitivity of traditional tests of gastrointestinal tract, and no
      consensus on the diagnostic algorithm. The aim of this study was to provide an
      algorithm for the diagnosis and treatment of PLR. There were no pathognomonic
      symptoms or findings, but the characteristic symptoms validate the Reflux Symptom
      Index and Reflux Findings Score as tools in the initial diagnosis. The first
      approach is empirical medical treatment for 3 month, based on endoscopic findings
      at laryngofiberscopy; then objective demonstration of reflux events using
      multichannel intraluminal impedance and pH monitoring. Proton pump inhibitors
      represent the mainstay of therapy for the patients with PLR, but they require a
      more aggressive and prolonged treatment than the patients with gastroesophageal
      symptoms.

PMID- 21870733
TI  - [Classification and staging systems for hilar cholangio-carcinoma (Klatskin
      tumors): clinical application and practical relevance].
AB  - Hilar cholangiocarcinomas or Klatskin tumors have been classified in 1975 by
      French surgeons Henri Bismuth and Marvin B. Corlette and this remains largely
      used in clinical practice. The authors present the TNM classification and the
      changes introduced by the sixth and seventh edition of Union for International
      Cancer Control regarding the tumors of the proximal bile duct and describe
      Blumgart classification for tumors of this site. The usefulness of these systems
      is assessed considering the last six years experience of the service.

PMID- 21870734
TI  - [Regeneration capacity of the peripheral nerve: experimental study--final
      results].
AB  - Any injury affecting peripheral nerve continuity is followed by a degenerative
      reaction from nerve itself and its muscle. Nerve regeneration is possible when
      the two ends are put in direct contact (direct suture), proximity (autologous or
      artificial grafts), or through muscle neurotization. The aim of this experimental
      study was to evaluate sciatic nerve degeneration and regeneration in rats after
      no suture (group 1), direct suture (group 2), nerve grafting (group 3) and muscle
      neurotization (group 4). Nerve samples were analyzed by optical microscopy at 8
      and 16 weeks after surgery, and nerve degeneration (group 1), axonal growth
      (group 2) and neuromuscular regeneration (group 4) were assessed. Optical
      microscopy and different staining techniques confirmed nerve degeneration,
      regeneration, and axonal growth in different moments. Cholinesterase test after
      direct muscle neurotization showed enzymatic activity at the level of muscle
      implantation of nerve fibers, indirectly confirming the presence of neuromuscular
      synapse.

PMID- 21870735
TI  - [Percutaneous nephrostomy complications in obstructive renal failure].
AB  - OBJECTIVES: The study aimed to identify the complications recorded at the
      patients with obstructive renal failure treated with percutaneous nephrostomy
      (PCN). MATERIAL AND METHOD: The retrospective study investigated the data of 244
      patients admitted in our department and treated with percutaneous nephrostomy for
      obstructive renal failure during January 2005 - December 2007. Demographical
      data, investigation, indication, complications and hospital stay were recorded.
      RESULTS: Median preoperative/discharge haematological values were hematocrit
      27.4% comparing to 25.8% and haemoglobin 9.9g% comparing to 9.3g%. An anaemic
      syndrome was noted at admission time in 161 (65.9%) patients and at discharge
      time 202 (82.8%). 126 (51.6%) patients were treated with blood transfusion with
      an average dose of 2.47 red blood cell units per patient. In 25 (10.1%) patients
      the nefrostomy tube was clamped in order to control the postoperative bleeding.
      The median hospitalization time was 8.7 days with a median ICU stay of 3.3 days.
      The recorded mortality was 3.2% (8 patients) with an average time of 5.8 days
      between the operatory time and exitus time. CONCLUSIONS: The most frequent causes
      of obstructive renal failure necessiting percutaneous nephrostomy are
      malignancies. Preoperative anaemic syndrome is aggravated in the postoperative
      period and frequently need red blood cell administration. In experienced hands,
      PCN catheter placement is safe and usually successful.

PMID- 21870736
TI  - [Subcutaneous fat tissue drainage in obese pregnant women after caesarean
      section].
AB  - The authors have analyzed the outcome of cesarean section celiotomy in obese
      pregnant women. The occurrence of postoperative wound infections, eventually
      dehiscence, in 2015 pregnant women who underwent caesarean section in a 3-year
      interval at the Craiova 1st Clinic of Obstetrics was studied. The analysis
      revealed the relation between postoperative wound infection and its topography,
      the type of fat tissue drainage (if done), and skin suture. The authors present a
      very effective method of subcutaneous drainage in obese pregnant women after
      cesarean section.

PMID- 21870737
TI  - [Ovarian tumors of low malignant potential (borderline ovarian tumors)].
AB  - Ovarian borderline tumors are rare, their good prognosis depending on their stage
      at the time of diagnosis, and the presence of invasive implants. There is little
      information on tumor type identified intra-surgically, as well as on the most
      favorable treatment in borderline ovarian tumors. AIM: To determine the criteria
      of identification and presurgery and intra-surgery differentiation of the ovarian
      borderline tumors from the invasive carcinoma and benign ovarian tumors. MATERIAL
      AND METHODS: This study included 54 patients with TPMS (ovarian borderline
      tumors) surgically treated in the past 22 years (January 1988-December 2009) at
      the 4th Gynecological Clinic of the lasi "Gr. T. Popa" University of Medicine and
      Pharmacy. In this interval 1,107 ovarian tumors: 575 benign, 478 malignant, and
      54 TPMS (4.87%) were recorded. The age of the patients with borderline tumors
      ranged between 20 and 78 years, mean age 46 years, and the histological types
      were: mucinous (27 cases), serous (18 cases), mixed (8 cases), and Brenner tumor
      (1 case). RESULTS: We have analyzed the distribution of these cases according to
      the time when surgical treatment was performed. The frequency of borderline
      ovarian tumors in our study is 4.87%, lower than in the literature. We believe
      that this low percentage in our study is due to missing the microscopic data in
      some macroscopic benign tumors. CONCLUSIONS: By this research we aimed at
      elaborating a therapeutic strategy for each case using with discernment the
      modern treatment (surgery, chemotherapy, radiotherapy), as well as new chemical
      drugs with the goal of obtaining better results and longer survival. There are no
      tumor markers which could predict the progression of a borderline ovarian tumor
      to invasive tumors, but the invasive course is only 0.7%.

PMID- 21870738
TI  - [Etiologic considerations of postlaryngectomy dysphagia].
AB  - Dysphagia following laryngeal surgery is a common and severe symptom. Two life
      threatening complications can compromise the patiens quality of life: pneumonia
      and malnutrition. Diagnostic procedures of swallowing disorders are represented
      by videofluoroscopic evaluation, CT scan and fiberoptics endoscopy. MATERIAL AND
      METHODS: A retrospective evaluation was performed in a sample of 261 patients
      undergoing laryngectomy, hospitalized in the E.N.T Clinic of "St. Spiridon"
      Hospital, between 2006 and 2010. Postlaryngectomy dysphagia was diagnosed in 74
      patients and was predominant in males (97.3%) aged between 50 and 60 years
      (37.8%). RESULTS: Main causes of dysphagia were pharingocutaneous fistulas, tumor
      recurrences, postoperative cervical infections and hipopharyngeal stenosis.
      CONCLUSIONS: This study reveled the predominance of dyphagia in rural male
      patients undergoing total laryngectomy. Gastroesophageal reflux can represents a
      favoring factor of this type of dysphagia.

PMID- 21870739
TI  - [Diagnostic problems in fetal echocardiographic examination. Observations on a
      lot of study during 2005-2010].
AB  - Echocardiography is the key diagnostic method in the diagnostics of structural
      heart pathologies. AIM: To underline some possible situations that may cause
      errors in ultrasound examination of the fetal heart. MATERIAL AND METHOD: We
      examined a number of 39,370 fetuses along a period of six years. The ultrasound
      scan was performed according with international standards of basic and extended
      cardiac scan. RESULTS: 442 of them (1.12%) were diagnosed with cardiac
      malformations. CONCLUSION: Ultrasound examination errors can cause false
      positive, false negative or incomplete diagnosis. Limitations in fetal
      echocardiography are related to the examiner experience to do an accurate
      diagnosis. The difficulty of assessing complex congenital heart lesion is
      increased. The unsatisfactory study should be repeated and sometimes the exact
      diagnosis requires sequential procedures. The aim is to define fetal heart
      anatomy and adise the family, in collaboration with neonatologist. The final
      results ia an optimal behavior for the fetus and newborn.

PMID- 21870740
TI  - [Assessment of visual function under treatment with topical antiglaucoma agents
      and systemic vasodilators. Clinical study on glaucoma patients].
AB  - The authors present some observations regarding the use of topical anti-glaucoma
      therapy and systemic vasodilators. MATERIAL AND METHODS: The study was carried
      out on a series of 996 glaucoma patients, of which 54.1% with primary open-angle
      glaucoma, 5.7% closed-angle glaucoma, and 17.6% with normal intraocular pressure.
      RESULTS: Intraocular pressure and visual field were assessed after the use of
      such therapeutic methods as carbonic anhydrase inhibitors (dorzolamide) and
      prostaglandin (latanoprost) and dorzolamide (cosopt) association. CONCLUSIONS:
      The favorable progression of glaucoma could be improved by using new
      etiopathogenic mechanisms and treatment approaches.

PMID- 21870741
TI  - [Low anterior resection of the rectum with total mesorectal excision--immediate
      results].
AB  - AIM: this study was aimed at analyzing the immediate postoperative course in
      rectal cancer patients who underwent a low anterior resection of the rectum with
      total mesorectal excision. MATERIAL AND METHODS: A retrospective study was
      carried out on a series of 75 patients operated between January 1, 2004 and
      December, 31 2010 at the 1lrd Surgical Unit of the Iasi "St. Spiridon" Hospital,.
      Low anterior resection of the rectum with total mesorectal excision was performed
      in all the patients. Data from medical files regarding the immediate
      postoperative course were analyzed. RESULTS: Neoadjuvant therapy was instituted
      in 32 patients. There were 28 mechanical colorectal anastomoses and 47 manual
      anastomoses. Protective ileostomy was performed in 46 cases, including I manual
      anastomosis and 35 mechanical anastomosis cases. Anastomotic fistulas occured in
      II patients (6 with manual suture and 5 with stapler). Wound complications were
      identified in 5 cases, while retraction of ileostomy in 2. Two patients died from
      anastomotic fistula causing abdominal sepsis and multiple organ failure. In both
      cases ileostomy was performed at the reintervention, concomitantly with drainage
      of the abdominal abscesses. CONCLUSIONS: Healing of the colorectal anastomosis
      remains the major problem with low anterior resection of the rectum. Protective
      ileostomy reduces the risk of serious complications in the event of anastomotic
      fistula.

PMID- 21870742
TI  - [Rare tumors of the neck--report of two cases].
AB  - Of the tumors of the neck some are very uncommon, difficult to diagnose both
      clinically and paraclinically. Two of the most rare tumors are osteolipoma and
      soft tissue sarcoma. We present 2 such cases admitted to and operated at the ENT
      Department of the Iasi "St. Spiridon" Emergency Hospital in the last 5 years,
      with emphasis on the atypical clinical and imaging features of these tumors.
      Surgery and histopathological examination were the methods used to make the
      diagnosis.

PMID- 21870743
TI  - [Resolution of inflammation--pharmacological aspects].
AB  - Inflammation is a fundamental biologic process evolutionally preserved by a germ
      line code. The interplay of the epigenetic with the environment directs the code
      to temporally distinct inflammatory responses, which can be acute or chronic. The
      aim of this study is to present new aspects regarding the resolution of
      inflammation. Acute inflammation normally resolves by mechanisms still somewhat
      elusive. Current evidence suggests that an active coordinated program initiated
      the first few hours after the inflammatory response begins and its failure lead
      to chronic inflammation. This process is essential for appropriate host
      responses, tissue protection and the return to homeostasis. Prostaglandins and
      leukotrienes are lipid mediators that play important roles in host defense and
      acute inflammation. Granulocytes promote the switch of arachidonic acid-derived
      prostaglandins and leukotrienes to lipoxins, active antiinflammatory and pro
      resolution mediators. The apoptosis of the neutrophils coincides with the
      biosynthesis of resolvins and protectins from omega-3 polyunsaturated fatty acids
      and releases anti-inflammatory and reparative cytokines. This information could
      lead to new treatments for inflammatory diseases.

PMID- 21870744
TI  - [PPARs: structure, mechanisms of action and control. Note I].
AB  - PPARs (peroxisome proliferator activated receptors) are proteine receptors that
      act as transcription factors activated by ligands. There are three known isoforms
      of PPARs (alpha, beta/delta, gamma) with similar modulated structure, consisting
      of distinct regions with specific functions. PPARs activate transcription of
      their target genes by forming cytoplasmatic heterodimers (PPARs:RXR) with his
      partner RXR (retinoid X receptor), and once translocated into the nucleus bind to
      specific DNA sequence called PPRE (peroxisome proliferator response elements) and
      modulate the expression of genes. Each PPAR is differently expressed in various
      tissues. Modulatory function of PPARs is induced by natural or synthetic ligand
      binding. Additional activator proteins are recruited to form a complex that
      coordinates and regulates the expression of many genes. Moreover, nuclear
      receptors' activity is also regulated by posttranslational changes.

PMID- 21870746
TI  - [Mathematical modelling of drug addiction].
AB  - AIM: To describe and assess the phenomenon of drug addiction by the use of a
      system of linear differential equations. MATERIAL AND METHODS: For analytical
      purposes, the study population (1020 individuals) was divided into three groups:
      likely to use drugs, drug users, and recovered (S-D model). RESULTS: The number
      of individuals likely to use drugs decreases with the increase in the number of
      infected ones; thus, in about 10 days, the number of infected individuals matches
      the number of those likely to use drugs. If the global parameters of the study
      model are changed, a more rapid increase in the number of infected individuals is
      noticed. Also noticed is the fact that the number of recoveries is likely to
      decrease with the increase in the number of infected individuals. CONCLUSIONS:
      Although numerical techniques are often preferable, the analytical ones have some
      advantages. Thus, an analytical approach may provide a deeper understanding of
      the mechanism of a given phenomenon, so it is more convenient to describe the
      state variables in terms of parameters than in terms of numerical approximation.
      To assess to role of hazard and uncertain associations in the future statistical
      methods will be used.

PMID- 21870745
TI  - [Assessment tumor markers by immunohistochemistry (Ki67, p53 and Bcl-2) on a
      cohort of patients with cervical cancer in various stages of evolution].
AB  - In defining new potential prognostic factors in cervical cancer, p53 protein
      expression, Ki67 or issues related to Bcl-2 oncogene involved in cellular
      apoptosis process, have been the subject of numerous publications. This paper
      aims to study with immunohistochemical methods, the way in which these factors
      are involved in influencing the prognosis of patients with cervical cancer. The
      study was conducted on 42 pieces operators from the same number of patients
      diagnosed with this disease, aged between 25-65 years and in different clinical
      stages. We used an experimental design type 2 (histopathological type squamous
      cell/adenocarcinoma) x 3 (degree of differentiation weak/ moderate/ well
      differentiated) x 4 (stage I/ II/ III /IV disease). Diagnosis was based on
      clinical examination and confirmed by histopathology, and hypothesis testing we
      used Kruskal-Wallis ANOVA test of ranks test, Mann-Whitney U test, chi2 test,
      Spearman's correlation test and crosstabs ranking difference. The results on the
      study group showed the prognostic value of both the proliferation marker Ki67 and
      p53 oncogene, the presence of tandem Ki67/p53 in cervical carcinoma meaning more
      so a poor prognosis, Bcl-2 overexpression was detected in none of the 42 cases
      investigated.

PMID- 21870747
TI  - [Macroscopic and microscopic lesions in bronchial asthma].
AB  - Bronchial asthma is a chronic inflammatory disease characterized by reversible
      airways obstruction, inflammation, and increased bronchial hyperresponsivennes.
      The aim of this study was to evaluate the macroscopic and microscopic airways
      lesions, using bronhoscopy followed by biopsy in 38 cases of Outpatient
      Department from Clinic of Pulmonary Diseases Iasi, investigated between January
      2005 - June 2008. Patients distribution according to the degree of severity was
      performed, using the international recommendations for asthma management of the
      Global Initiative for Asthma (GINA): intermittent (n=7 patients), mild persistent
      (n=10 patients), moderate persistent (n=16 patients), and severe persistent (n=5
      patients). 23,68% of patients had a chronic disease of more than 15 years. The
      endoscopic changes of the peripheral airways were represented by edema,
      congestion, bronchial stenosis and mucus hypersecretion. Microscopic routine exam
      showed epithelial lesions (epithelial desquamation, goblet cell hyperplasia,
      squamous metaplasia), basement membrane thickening, edema, increased
      vascularisation, glandular and muscular hypertrophy and bronchial inflammatory
      infiltrate. Although bronhoscopy exam offers important information regarding
      changes of the airway mucosa in bronchial asthma, it concomitantly provide
      bioptic control, as microscopic examination still represents the "gold standard"
      assessment of bronchial wall remodeling process.

PMID- 21870748
TI  - [Medical-social aspects of medical staff migration].
AB  - The migration of the medical staff represents an increasingly worring reason for
      romanian health policy-makers. According to the Ministry of Health, in 2009 year,
      the human resources indicators pointed out 26.5 physicians/ 10,000 inhabitants
      (whereas the European Union average was 32.8) and 60.4 nurses and midwives
      (whereas the European Union average was 108.5). Between 2007-2010, over 9000
      physicians requested professional certificates in order to practice abroad and
      the majority have left the country. This phenomenon is related to the Romania's
      entrance in European Union and it is supposed to continue in the coming years.
      The direct consequences of the migration of the medical staff consist of
      significant differences between the country's regions in the health workforce
      distribution, the most affected by the critical shortage of health service
      providers being the North-Eastern region, especially in rural area. In order to
      limit the migration phenomenon, the Ministry of Health elaborated some strategies
      and workforce policies on medium and long-term, but the results will be difficult
      to assess.

PMID- 21870749
TI  - [Some risk factors in breast tumour etiology. Observations in Iasi County between
      2006 and 2010].
AB  - THE AIM OF STUDY: To assess some risk factors and their involvement in female
      breast tumours etiology. MATERIAL AND METHODS: The study was performed on a
      sample of 67 patients registered with breast tumours, at family phisicians'
      offices from Iasi, Romania. RESULTS: Some risk factors were defined such as:
      nuliparity (20.8%) and first pregnancy after age 30 (34.3%); fibrous mastopathy
      in personal history (73.1% of cases with breast cancer) and breast cancer in
      siblings of first (8.9%) and second grade (11.9%). Relative to lifestyle,
      sedentary life was remarked in 59.2% of patients; modification of circadian
      rhythm in 28.3%, and excesive caffeine consumption in 80.9% of cases.
      CONCLUSIONS: Further prevention and educational programs on breast tumoural risk
      factors are needed in Romania, even at female teenage, performed by family
      physician.

PMID- 21870750
TI  - [Comparative clinical-epidemiological assessments of road traffic accidents:
      emergency room observations in three counties of Moldavia, Romania, during 2005
      2010].
AB  - AIM: To assess road traffic injuries according to some descriptive parameters.
      MATERIAL AND METHODS: The study was carried out on a series of 5374 patients
      admitted to emergency rooms at Iasi (n=3050), Botosani (n=1187), and Vaslui
      (n=l137), between 2005 and 2010. RESULTS: Most frequently, the patient was a
      young, male adult, with cranial cerebral trauma, leg fracture, forearm contusion,
      or polytrauma, presenting to the emergency room most commonly in the month of
      August, weekends, and interval noon-dawn interval. CONCLUSIONS: The impact of
      road trauma epidemic would facilitate a better adaptation of the medical staff to
      case dynamics and increase the efficacy of primary prevention programs.

PMID- 21870751
TI  - [Assessment of consumer satisfaction with public health and medical services in
      the city of Iasi].
AB  - AIM: The study was designed to assess patient satisfaction regarding the quality
      of medical care delivered in 2010, the financial accessibility of the used
      services, the time span accessibility to the services used, doctor-patient
      relationship, and quality of health services. MATERIALS AND METHOD: This study
      was carried out on a series of 150 randomly selected patients, age-range l8 to 70
      years. These patients were asked to fill out a 44-item questionnaire including
      demographic data (age, education, environment--rural or urban area, difficult
      financial situation) and questions on the quality of the delivered medical care
      and the performance of the qualified medical staff. RESULTS AND DISCUSSION: The
      global assessment of the quality of health services shows that it is mainly
      satisfactory (42.00%) and good (31.33%). The primary health services (family
      medicine) are mostly regarded as very good (38.00%), good (28.67%) and
      satisfactory (24.67%). As to the specialized outpatient services, most
      investigated subjects found them satisfactory (32.67%), good (27.33%), and poor
      and very poor (8.00%). A percentage of 35.33 of the respondents think that the
      services provided in hospitals are satisfactory, 18.00% good and 9.33% very good.
      Drug administration was considered satisfactory by 37.33%, while 22.00% and 12.6%
      believe it to be good and very good, respectively. CONCLUSIONS: The regular
      application of questionnaires to measure patient satisfaction and the setting up
      of a system for measuring the quality of medical care will improve quality of the
      health services.

PMID- 21870752
TI  - [Carbapenem resistance in Klebsiella pneumoniae clinical isolates from urinary
      tract infections].
AB  - Resistance to carbapenems by KPC (Klebsiella pneumoniae carbapenemase) production
      in Klebsiella pneumoniae clinical isolates was first described ten years ago in
      the U.S.A. and recently reported in other countries. This enzyme inactivates all
      beta-lactam antibiotics and is associated with fluoroquinolone and aminoglycoside
      resistance. MATERIAL AND METHODS: We investigated the carbapenem resistance in
      498 Escherichia coli and Klebsiella pneumoniae strains isolated from urinary
      tract infections during 2009 in the lasi "Dr. C. I. Parhon" Clinical Hospital.
      Antimicrobial susceptibility testing was performed according to CLSI guidelines.
      To detect ESBL (extended spectrum beta-lactamase) and KPC production we used
      phenotypic tests and molecular biology methods (PCR). RESULTS: From all tested
      strains, only two K. pneumoniae strains showed modified susceptibility to
      carbapenems. The modified Hodge test was positive for the strain resistant to
      ertapenem, meropenem, imipenem (KA) and negative for the strain resistant only to
      ertapenem (K(B)). Both KA and K(B) isolates were negative for blaKPC and blaTEM
      genes, but harbored blaSHV and bla(CTX-M) genes, respectively. CONCLUSIONS: We
      report the first carbapenem resistant K. pneumoniae strains from Northeast
      Romania. The resistance is not mediated by KPC-carbapenemase; the possibility of
      dual mechanisms through cefalosporinases production and porins loss is suggested.

PMID- 21870753
TI  - [Antimicrobial resistance of Streptococcus pneumoniae, 2003-2009].
AB  - Streptococcus pneumoniae is the most important respiratory tract pathogen in
      otitis, sinusitis, bronchitis, and community-acquired pneumonia. MATERIAL AND
      METHODS: A total of 155 patient isolates of S. pneumoniae were collected between
      February 2003 and December 2009 from the Iasi "Sf. Parascheva" Infectious
      Diseases Hospital. Susceptibility to antibiotics was assessed by disk diffusion
      method (CLSI 2003-2008); minimum inhibitory concentrations (MIC) to penicillin
      and cefotaxime were determined by broth dilution method or E-test method.
      RESULTS: Of these isolates, 32.6% were penicillin non-susceptible (MIC > or =
      0.12 microg/mL for nonmeningeal isolates before 2008 and all meningeal isolates
      and MIC > or =2 microg/mL for nonmeningeal isolates after 2008). The percentage
      of penicillin resistance increased from 0% to a maximum of 50% in 2008.
      Resistance rates (intermediate and resistant strains) among non-beta-lactam
      agents were as follows: macrolides, 30.9%; clindamycin, 9%; tetracycline, 34.3%;
      chloramphenicol, 2.1%; and trimethoprim-sulfamethoxazole, 57.5%. No resistance to
      vancomycin, linezolid and quinupristin-dalfopristin was observed. Resistance to
      non-beta-lactam antibiotics was higher among penicillin-resistant strains than
      penicillin-susceptible strains. Overall, antimicrobial resistance was higher
      among isolates from respiratory tract comparing with isolates from cerebrospinal
      fluid and blood. CONCLUSIONS: Resistance rates with S. pneumoniae have markedly
      increased in Romania during the last years. Pneumococcal isolates from lasi,
      Romania are often resistant to beta-lactams and available non-beta-lactam agents,
      especially if penicillin non-susceptible.

PMID- 21870754
TI  - [Surface characteristics of the acrylic resins according to the polishing
      methods].
AB  - AIM: The objective of this study was to evaluate the effect of the polishing
      technique and glazing on the porosity of the dental resins. MATERIAL AND METHODS:
      The studied resins were: Castapress/Vertex, Prothyl Hot/Zermack, Rapid
      Simplified/Vertex, Duracryl Plus/Spofa Dental, Vertex-Soft/Vertex, Superacryl
      Plus/Spofa Dental. Thirty specimens, five for every resin, of 50/25/2 cm in size
      were done. One surface of each sample was polished with extrahard tungsten
      carbide burs, the other surface being polished with extrahard extrafine and
      diamond burs. The final polishing was done using a conventional method: pumice,
      water and lathe bristle brush for 90 seconds, 1500 rpm and soft leather polishing
      wheel for 90 seconds, 3000 rpm. Twenty surfaces were glazed after polishing with
      Glaze/Bosworth. Vertex Soft specimens were not polished because this is a
      resilient material. Surface porosity of the acrylic resin specimens was measured
      by optical microscopy. RESULTS: The lowest porosity was obtained by conventional
      polishing combined with glazing techniques. No differences between glazed and
      non/glazed self-curing resin specimens were noticed, but there were differences
      between self-curing and heat-curing resins. CONCLUSIONS: Conventional lathe
      polishing method is an effective and reliable technique for polishing dental
      resins. Specimens of self-curing resin had a higher porosity than heat curing
      resin following the same surface treatment. Higher surface smoothness was
      obtained by conventional lathe polishing completed by glazing.

PMID- 21870755
TI  - [Prevention of infection transmission in dental laboratories].
AB  - The professional activity in a dental laboratory is associated with a high risk
      for infection transmission through the manipulation of impressions and prostheses
      contaminated with patients' saliva and blood. AIM: To assess the compliance of
      dental technicians in lasi town dental laboratories with the methods used for
      preventing infection transmission in their practices. MATERIAL AND METHODS: This
      questionnaire-based survey included 61 dental technicians aged 22 to 58 years
      from 29 dental laboratories. The 17 questions were related to the protection
      equipment, air ventilation, and disinfection of surfaces, instruments,
      impressions, and prostheses. SPSS 14 system, Chi-Square test were used for data
      analysis, and the levels of statistical significance were set at p < 0.05.
      RESULTS: 90.2% of the subjects claim the need of prosthetic items disinfection
      upon arrival at the laboratory from the dental office (p < 0.05). The protection
      equipment is used by 49.1% of the dental technicians included in this survey
      (full equipment 18.0%, safety glasses 45.9%, mask 37.7%, rubber gloves 19.6%).
      59.1% of the laboratories are provided with air ventilation, while surface
      disinfection is common practice in 85.2%. Of the study subjects 62.1% disinfect
      the impressions, 26.1% the final prosthesis, and 25.0% disinfect the
      interocclusal registrations (p < 0.05). CONCLUSIONS: Educational programs aimed
      at increasing dental technicians' awareness of infection control by adopting the
      most effective prevention measures are essential for reducing the incidence of
      technicians, dentists, and patients; exposure.

PMID- 21870756
TI  - [The platysma myocutaneous flap (PMF) for reconstruction of defects after
      extended parotidectomy].
AB  - In order to reestablish the facial symmetry after the tumor removal, we can use
      sternocleidomastoid muscle transposition, dermis-fat graft, superficial
      musculoaponeurotic system (SMAS) plication, temporoparietal fascia flaps,
      microvascular free flaps and the platysma muscle flap. The technic depends on the
      size of the defect. MATERIAL AND METHODS: In this study we present our results of
      using a superiorly based platysma myocutaneous flap for reconstruction of defects
      after extended parotidectomy. The patients were treated for malign tumor of
      parotid gland which invaded the skin. RESULTS: All flaps were readily harvested
      at the time of tumor resection. Only two patients presented venous congestion. No
      flap was lost. There was no morbidity of donor site. The cosmetic outcome was
      satisfactory. DISCUSSION: The platysma myocutaneous flap is an alternative to
      more complex reconstructive technics, such as free flap transfer, and gives a
      satisfactory cosmetic result. CONCLUSIONS: The platysma myocutaneous flap is easy
      to harvest and has low donor site morbidity. The main disadvantage is represented
      by the vascularity problems.

PMID- 21870757
TI  - [Cutaneous carcinoma of the face. Clinical and histopathological forms.
      Retrospective study of 308 cases].
AB  - Cutaneous carcinomas are the most frequent malignant tumors, the majority of them
      being located on the face, scalp and back. AIM: To assess the clinical
      presentation and pathology aspects of the patients with face skin carcinomas
      admitted to our clinic. MATERIAL AND METHODS: The retrospective study was carried
      out on a series of 308 patients diagnosed and treated for cutaneous carcinoma of
      the face in the Department of Oral and Facial Surgery of lasi over a period of 5
      years (January 2006 - December 2010). The following parameters were analyzed:
      demographic data, size and location of the tumor, clinical presentation, and
      pathology aspects. RESULTS: Basal cell carcinoma accounted for 75.97% of the
      cases, the nodular, superficial and morphea types being the most common. As to
      the microscopic aspects, the nodular/solid, superficial, and basosquamous
      (metatypical) types were the most frequent. The squamous-cell carcinoma
      represented 18.18%, mainly in the ulcero-vegetant and nodular forms. The
      moderately and well differentiated forms prevailed. Carcinomas of the skin
      adnexes as well as Merkel cell carcinomas were the most rare (4.22% and 0.65%,
      respectively). CONCLUSIONS: The face is the most common location of the cutaneous
      carcinomas requiring early diagnosis and treatment as a key factor to favorable
      long term outcome.

PMID- 21870758
TI  - [Effect of adverse oral habits on the development of the dentomaxillary system].
AB  - Main features of the dentomaxillary system (breathing, chewing, swallowing) are
      provided by the rhythmic movements of the mandible, tongue, lips, mimic muscles,
      learned during ontogenesis and coordinated neuromusculary and largely automated.
      AIM: The aim of our study was to prove the role of oral habits in the development
      of dentomaxillary anomalies. We made experimental investigations--model studies,
      fotostatic test for face and side face, radiological examinations, clinical
      general and ENT exam for accurately assess of the factors which contribute to the
      emergence and development of dentomaxillary anomalies. MATERIAL AND METHODS: The
      study group consisted of 175 children (94 girls and 81 boys) aged between 7 and
      14 years. We made individual sheets for recording neuromuscular and oropharyngeal
      balance starting from a patient's overall clinical appearance. RESULTS: The
      diagnosis of most teenagers was first Angle's class of malocclusion with tongue
      thrusting and mouth breathing. Oral habits disrupt the muscular balance and bone
      growth producing changes in the dental arch and ocllusal characteristics. The
      high prevalence of dentomaxillary anomalies (52.57%) and obvious
      interrelationship with functional imbalances of the dentomaxillary system (62.82%
      of subjects examined) supports the implication of functional factors in those
      etiology. CONCLUSIONS: Suppression of vicious habits by methods of awareness,
      myogymnastic and functional reducing exercises are the first steps of early
      functional treatment for dentomaxillary anomalies.

PMID- 21870759
TI  - [Dermoid cyst of the parotid gland].
AB  - Dermoid cyst of the parotid gland is a rare clinical entity. Definitive clinical
      diagnosis is often difficult to determine preoperatively because of the lack of
      pathognomonic features. The most frequent location of a parotid dermoid cyst is a
      triangular area lying above the pinna. Imaging studies do not definitely diagnose
      a parotid dermoid cyst. Although parotid dermoid cyst is (generally) well
      encapsulated, complete removal of the cyst wall is not sufficient to cure it, so
      it is mandatory to perform careful excision of the cyst by parotidectomy, in
      terms of preserving facial nerve integrity. Histopathology of the parotid gland
      tumor removed by parotidectomy makes a diagnosis of certainty, by revealing a
      cyst wall with keratinization of the squamous epithelium and the presence of skin
      annexes (hair follicles, sweat glands, sebaceous glands). We present a rare case
      of parotid dermoid cyst in a 21-year-old male patient with symptoms and imaging
      rather suggestive of arch I branchial cyst and a brief review of data in the
      medical literature of the last 20 years.

PMID- 21870760
TI  - [Malherbe's calcifying epithelioma--comment on two clinical cases].
AB  - Malherbe's calcifying epithelioma (also called trichomatricoma, pilomatrixoma or
      pilomatricoma) is an uncommon benign cutaneous tumor, which takes the form of a
      solitary, firm, asymptomatic, slowly growing nodule, developed subcutaneously on
      the face, neck, or proximal upper extremity. With an incidence of 1/800-1000
      cutaneous tumors, pilomatricoma is more common in the first two decades of life,
      predominantly affecting the women. Multiple locations and associations between
      this entity and other diseases such as Steinert's myotonic dystrophy or Gardner
      syndrome have been described in the literature. The clinical diagnosis is often
      difficult, most cases being mistaken as sebaceous cysts. The treatment of choice
      is surgical excision. Incomplete surgical excision can be followed by local
      recurrence because most lesions are poorly defined; therefore, patients should be
      monitored after surgical excision to prevent this from happening. We present two
      cases admitted in 2010 and 2011 to the Iasi Department of Oral and Maxillo-Facial
      Surgery: a 55-year-old female patient with a Malherbe's calcifying epithelioma
      located in the left temporal region, and a 51-year-old female patient with the
      same disease but located in the left masseter region.

PMID- 21870761
TI  - [Studies regarding chemical composition of lavender volatile oils].
AB  - AIM: In this paper, we studied comparatively volatile fractions obtained by
      hydrodistillation from 5 samples of lavender flowers (L. angustifolia ssp.
      angustifolia, L. hybrida, L. angustifolia spp. pyrenaica, L. angustifolia spp.
      angustifolia cv. Munstead and cv. Hidcote blue) cultivated during 2009 in the
      Botanical Garden from Galati. MATERIAL AND METHODS: The essential oils have been
      characterized using gas-chromatography and mass spectroscopy analysis (GC-MS).
      RESULTS: The main compounds in all lavender volatile oils were: linalool (20.60%
      35.99%), linalyl acetate (12.58%-19.65%), lavandulyl acetate (3.74%-10.48%), t-p3
      ocimene (1.26%-9.23%), a-terpineol (3.67%-6.73%), nerol (0.81%-3.32%), neryl
      acetate (0.95%-3.64%) and beta-caryophyllene (0.93%-2.43%). CONCLUSIONS: None of
      the separated volatile fractions met the minimal quality parameters for the
      standard volatile oil of fine lavender used in aromatherapy. Low concentration in
      monoterpene esthers could be explained by the fact that, on one hand, the average
      daily temperature during the blooming period is below the one from Mediterranean
      Sea area, and, on the other hand, the city of Galati is only 42 meters above the
      sea level (the volatile oil from fine lavender used in aromatherapy is obtained
      from plants cultivated at 800-1200 meters altitude).

PMID- 21870762
TI  - [Chemical composition of essential oil obtained from Romanian fennel fruits].
AB  - For therapeutical purposes, fennel (Foeniculum vulgare Mill.), an important
      aromatic plant, is used for its expectorant, antispasmodic, carminative and
      diuretic properties. The chemical composition, especially of the volatile
      fraction, depends on the origin of the plant, and the ecological and
      environmental conditions in which it grows. AIM: To determine the chemical
      composition of the volatile fractions obtained from fennel fruits (Foeniculum
      vulgare Mill.) available on the Romanian market. MATERIAL AND METHODS: The
      essential oils obtained from dried fruits by hydrodistillation have been
      characterized by using gas chromatography and mass spectroscopy (GC-MS). RESULTS:
      In all oils, the main components were: trans-anethole (9.72-56.57%), fenchone
      (7.72-34.66%) and estragole (4.69-49.04%). CONCLUSIONS: The essential oil from
      fennel samples showed an inadequate chemical profile for aromatherapy purposes.

PMID- 21870763
TI  - [Validation of a HPLC method for ochratoxin A determination].
AB  - Ochratoxin A is a mycotoxin produced by various species of Aspergillus and
      Penicillium. Ochratoxin A has been detected in cereals and cereal products,
      coffee beans, beer, wine, spices, pig's kidney and cow's milk. For ochratoxin A,
      a HPLC method was developed and validated. Ochratoxin A was determined by RP
      HPLC, using a liquid chromatograph type HP 1090 Series II, equiped with a
      fluorescence detector. The analysis was performed with a Phenomenex column, type
      Luna C18(2) 100A (150 x 4.6 mm; 5 microm) with a mobile phase consisting of a
      mixture of acetonitrile/water/acid acetic (99/99/2), a flow of 0.7 mL/min. For
      detection, the wavelenght of excitation was 228 nm and wavelenght of emision was
      423 nm. The calibration graph was linear in 6.25-50 ng/mL concentration range (r2
      = 0,9991). The detection limits was 1.6 ng/mL and the quantification limit was
      4.9 ng/mL. The method precision (RSD = 2.4975%) and the accuracy (recovery was
      100.1%) were studied. The HPLC method was applyed for ochratoxin A from food
      samples with good results.

PMID- 21870764
TI  - Optimization of topical gels with betamethasone dipropionate: selection of gel
      forming and optimal cosolvent system.
AB  - The purpose of these studies was to develop a 0.05% betamethasone gel
      characterized by physical-chemical stability and good release properties. The
      preliminary studies were designed to select the gel-forming agents and the
      excipients compatible with betamethasone dipropionate. In order to formulate a
      clear gel without particles of drug substances in suspension, a solvent system
      for the drug substance was selected. The content of drug substance released, the
      rheological and in vitro release tests were the tools used for the optimal
      formulation selection. A stable carbomer gel was obtained by solubilization of
      betamethasone dipropionate in a vehicle composed by 40% PEG 400, 10% ethanol and
      5% Transcutol.

PMID- 21870765
TI  - [Nitrates and nitrites in meat products--nitrosamines precursors].
AB  - AIM: To determine the content in nitrates and nitrites and the formation of two
      nitrosamines (N-nitrosodimethylamine--NDMA, and N-nitrosodiethylaamine--NDEA) in
      samples of chicken ham, dry Banat salami, dry French salami, traditional Romania
      sausages, and pork pastrami. MATERIAL AND METHODS: Nitrites were determined by
      spectrophotometry with Peter-Griess reagent, and nitrates by the same method
      after reduction to nitrites with cadmium powder. High performance liquid
      chromatography with UV detection was used to determine nitrosamines. RESULTS: The
      initial concentration of nitrates, nitrites, NDMA and NDEA in the samples ranged
      as follows: 14.10-60.40 mg NO3/kg, 2.70-26.70 mg NO2/kg, from non-detectable to
      0.90 microg NDMA/kg, and from non-detectable to 0.27 microg NDEA/kg,
      respectively. After 28 days the concentrations were: 3.24-17.1 mg NO3/kg, 0.04 
      1.87 mg NO2/kg, 0.8-29 microg NDMA/kg, and 11.6-61.9 microg NDEA/kg,
      respectively. CONCLUSIONS: The decreased nitrate and nitrite and increased NDMA
      and NDEA concentrations prove that in food products nitrosamines are formed due
      to residual nitrite during their preservation. The determination of nitrasamines
      revealed levels much above the admitted maximal concentration for these food
      products.

PMID- 21870766
TI  - Protective effects of selenium on acrylamide toxicity in the liver of the rat.
      Effects on the oxidative stress.
AB  - Acrylamide (AA), obtained for the first time by Moureu in Germany in 1893, is
      presently used as polyacrylamide in water treatment and wastewater treatment,
      paper and pulp processing, mineral processing, crude-oil production processes.
      Acrylamide is a chemical product formed when frying, roasting, grilling or baking
      carbohydrate-rich foods at temperatures above 120 degrees C. Acrylamide is thus
      found in a number of foods, such as bread, crisps, French fries and coffee.
      Tobacco smoking also generates substantial amounts of acrylamide. Acrylamide
      administration is associated with significant increase of oxidative stress
      parameters; acrylamide caused disturbances in the oxidative status and enzyme
      activities and the effect was pronounced with the high doses. MATERIAL AND
      METHODS: This study investigates the effect of selenium (as sodium selenite and
      as a selenium dietary supplements--Celnium) on the oxidative stress in Wistar
      rats which received high doses of acrylamide. RESULTS: The administration of
      sodium selenite and selenium dietary supplements (Celnium) significantly
      increased GSH and GPx levels and decreased MDA compared to group which received
      only acrylamide. CONCLUSIONS: Our results show that sodium selenite and selenium
      dietary supplements (Celnium) can partially prevent the biochemical changes in
      the liver of the rats which received high doses of acrylamide.

PMID- 21870767
TI  - [Behavioral correlations of gradual forced administration of psychoactive drugs].
AB  - The study was aimed at evaluating the behavioral correlations of the forced
      administration of psychoactive drugs. Wistar rats received the following drugs in
      elevated doses (over 4 days, i. p.): (i) physiological saline (control; 0.1-0.2
      0.4-0.8 ml/rat), (ii) psychostimulant amphetamine (0.5-1.0--2.0-4.0 mg/kg); (iii)
      opioid analgetic fentanyl (0.00625-0.0125--0.025-0.05 mg/kg), (iv) ethanol 40%
      solution (0.5-1.0--2.0-4.0 g/kg), (v) barbiturate sodium ethaminal (2.5-5--10-20
      mg/kg); and(vi) synthetic glucocorticoid dexamethasone (0.5-1.0--2.0-4.0 mg/kg).
      The forced regime of drug administration led to gradual load of the organism and
      prevented drug tolerance. The dynamics of self-stimulation reaction of the
      lateral hypothalamus was registered every day over drug administration period and
      revealed the following regularities: (I) dose-dependent effect of psychostimulant
      amphetamine and opioid analgetic fentanyl; (II) dexamethasone modulated self
      stimulation, increasing (2 day, 1 mg/kg) or decreasing it (3 day, 2 mg/kg); (III)
      ethanol (1-2 g/kg) activated self-stimulation slightly; (IV) sodium ethaminal
      slightly inhibited self-stimulation and increased the thresholds of self
      stimulation. In 24 h and 72 h after the last administration of drugs, the rat
      behavior was assessed in open field, elevated plus maze, resident-intruder
      paradigm, and Porsolt's test. In the open field, significant signs of post
      intoxication exposure of psychoactive drugs were revealed, which were registered
      for 24-72 h after drug withdrawal. The withdrawal of drugs was accompanied with
      reduction (in 24 h) and subsequent recovery (in 72 h) of the vertical motor
      activity, exploration behavior, and emotionality. The anxiety indexes were
      increased up to the 3rd day after withdrawal. The antidepressant effect was also
      increased. The system of aggression-defense was restored only in rats treated
      with ethanol. The indexes of individual behavior and communicability in the post
      intoxication period were decreased as well. It is suggested that the forced
      regime of drug administration in increasing doses with subsequent withdrawal of
      drug injections is a suitable method to evaluate the behavioral elements of drug
      dependence.

PMID- 21870768
TI  - [Reamberin administration for early postnarcosis recovery in children].
AB  - The possibility of using 1.5% succinic acid solution (reamberin) in order to
      activate recovery from anesthesia was studied in a group of 91 patients aged 1-14
      years. Based on clinical data and BIS-index, it is established that the
      administration of reamberin during exit from anesthesia stage shortens the wake
      up period, decreases the time of restoration of the motor activity and adequate
      respiration, and accelerates brain function recovery.

PMID- 21870769
TI  - [Cardiotropic activity of synthetic peptide CH3CO-Lys-Lys-Arg-Arg-NH2
      (protectin)].
AB  - Peptide CH3CO-Lys-Lys-Arg-Arg-NH2 (protectin) was synthesized and its activity
      was studied on the model of experimental myocardial infarction in rats in
      comparison to the reference antihypoxant drug riboxin. Intranasal injections
      ofprotectin at doses within 2-20 microg/kg once a day by course of 7 days
      produced a pronounced anti-ischemic action, improved coronary circulation of the
      blood, increases contractile activity of myocardium, reduced intensity of lipid
      peroxidation, and improved antioxidant protection. In some respects (improved
      coronary circulation of the blood, increased antioxidant protection), protectin
      was more effective than riboxin.

PMID- 21870770
TI  - [Effect of mexidol on combined vascular pathology of brain and heart].
AB  - The effect of mexidol on cerebral blood flow under conditions of experimental
      myocardial infarction and combined disturbances of cerebral and coronary
      perfusion in comparison with intact and false-operated rats and rats after global
      transient ischemia of brain was studied. It is established that mexidol (200
      mg/kg) more prominently enhances the blood flow in the parietal region of brain
      cortex of rats with combined ischemia of brain and heart as compared to intact
      rats and rats after experimental myocardial infarction. Under conditions of
      combined pathology, mexidol produces the same cerebrovascular effect as that in
      animals with cerebral ischemia.

PMID- 21870771
TI  - [Influence of hemicellulose based anticoagulant on male rat reproductive
      function].
AB  - Results of estimation of the effect of a new hemicellulose-based anticoagulant
      drug on the reproductive function of white male rats are presented. No negative
      impact on the fertility and breed was observed for the drug administered in doses
      of 5 and 25 mg/kg. However, in a dose of 50 mg/kg, the new drug negatively
      affected spermatogenesis and decrease the reproductive function of male rats.

PMID- 21870772
TI  - [Effect of fullerene C60 on functional activity of phagocytic cells].
AB  - The effect of aqueous dispersion of fullerene C60 (FC60) on the functional
      activity of cells involved in the phagocytosis reactions was studied. FC60 (0.01
      microM/l and 0.1 microM/l) produced mainly negative effects on the activity
      ofnonspecific immunity cells by inhibiting the myeloperoxidase enzymatic
      activity, decreased the level of induced chemiluminescence, and suppressed the
      expression of molecules CD54 involved in the adhesion. The only exception was a
      slight stimulating effect on the NBT test. The results indicate the FC60
      influences various stages and mechanisms of phagocytosis.

PMID- 21870773
TI  - [Pharmacokinetics of domestic actoprotector drug Metaprot in healthy volunteers].
AB  - Pharmacokinetics of the actoprotector Metaprot, an original Russian drug, has
      been studied in a group of healthy adult volunteers. Metaprot in capsules was
      administrated orally as a single dose of 250 mg. The concentration of the active
      substance (ethylthiobenzimidazole) in the blood serum was determined by high
      performance liquid chromatography (HPLC) with UV detection. The pharmacokinetic
      parameters were calculated by the model-independent method. The peak
      concentration of ethylthiobenzimidazole in plasma was Cmax = 0.91 +/- 1.05
      microg/ml and the average time to peak concentration was t(max) = 1.06 +/- 0.16
      h. A polymodal character of the distribution of pharmacokinetic parameters in the
      test group was revealed.

PMID- 21870774
TI  - [Bioavailability and metabolism of flavonoids].
AB  - Published data about bioavailability and metabolism of flavonoids are reviewed.
      Information concerning the absorption of flavonoids in a digestive path and the
      participation of microorganisms in their hydrolysis is summarized. Parameters of
      pharmacokinetics are presented for the main classes of flavonoids, including
      flavanes (flavan-3-ols), anthocyans, flavones, flavonols, and flavanones.

PMID- 21870775
TI  - [Problems in treating influenza and acute respiratory infection in children].
AB  - Results of an investigation of the efficiency of several antiviral medications in
      children are presented. Mechanisms of action of etiotropic chemotherapeutic
      medications are described. Interferons and interferon inductors are characterized
      and the results of clinical administration of classical interferon inductor
      cycloferon are reported. Detailed descriptions of immunotropic drugs recommended
      for use in children are presented.

PMID- 21870776
TI  - Stick-slip of evaporating droplets: substrate hydrophobicity and nanoparticle
      concentration.
AB  - The dynamics of the three-phase contact line for water and ethanol is
      experimentally investigated using substrates of various hydrophobicities.
      Different evolutions of the droplet profile (contact line, R, and contact angle,
      theta) are found to be dependent on the hydrophobicity of the substrate. A simple
      theoretical approach based on the unbalanced Young force is used to explain the
      depinning of the contact line on hydrophilic surfaces or the monotonic slip on
      hydrophobic substrates. The second part of the article involves the addition of
      different quantities of titanium oxide nanoparticles to water, and a comparison
      of the evaporative behavior of these novel fluids with the base liquid (water) on
      substrates varying in hydrophobicity (i.e., silicon, Cytop, and PTFE) is
      presented. The observed stick-slip behavior is found to be dependent on the
      nanoparticle concentration. The evaporation rate is closely related to the
      dynamics of the contact line. These findings may have an important impact when
      considering the evaporation of droplets on different substrates and/or those
      containing nanoparticles.

PMID- 21870777
TI  - Improved templated fluorogenic probes enhance the analysis of closely related
      pathogenic bacteria by microscopy and flow cytometry.
AB  - Templated fluorescence activation has recently emerged as a promising molecular
      approach to detect and differentiate nucleic acid sequences in vitro and in
      cells. Here, we describe the application of a reductive quencher release strategy
      to the taxonomic analysis of Gram-negative bacteria by targeting a single
      nucleotide difference in their 16S rRNA in a two-color assay. For this purpose,
      it was necessary to develop a release linker containing a quencher suitable for
      red and near-infrared fluorophores, and to improve methods for the delivery of
      probes into cells. A cyanine-dye labeled oligonucleotide probe containing the new
      quencher-release linker showed unprecedentedly low background signal and high
      fluorescence turn-on ratios. The combination of a fluorescein-containing and a
      near-IR emitting probe discriminated E. coli from S. enterica despite nearly
      identical ribosomal target sequences. Two-color analysis by microscopy and the
      first successful discrimination of bacteria by two-color flow cytometry with
      templated reactive probes are described.

PMID- 21870778
TI  - Phase transitions of AlFeO3 and GaFeO3 from the chiral orthorhombic (Pna2(1))
      structure to the rhombohedral (R3c) structure.
AB  - AlFeO(3) and GaFeO(3), which crystallize in a chiral orthorhombic (Pna2(1))
      structure, transform to a rhombohedral (R3c) structure when subjected to ball
      milling. There is a distinct difference between the transformations of AlFeO(3)
      and GaFeO(3). AlFeO(3) first transforms to an orthorhombic P2(1)2(1)2(1)
      structure followed by its transformation to the R3c structure, while GaFeO(3)
      goes directly to the R3c structure. The transformations have been characterized
      by X-ray diffraction and Raman spectroscopy. Magnetic properties of Pna2(1) and
      the transformed phases show significant differences. It is noteworthy that
      partial substitution of aluminum by gallium in AlFeO(3) as in
      Al(0.5)Ga(0.5)FeO(3) eliminates the intermediate P2(1)2(1)2(1) phase, causing
      direct transformation of the Pna2(1) structure to the R3c structure. All of the
      transformations are thermodynamically first-order associated with significant
      changes in volume. We have used first-principles simulations to determine the
      pressure-dependent properties of AlFeO(3) and GaFeO(3) in orthorhombic and
      corundum structures and have estimated the critical pressures for the structural
      phase transition between the two structures. On the basis of this information, we
      also comment on the differences in the behavior of AlFeO(3) and GaFeO(3) under
      ball-milling.

PMID- 21870779
TI  - Polar fluorenes and spirobifluorenes: fluorescence and fluorescence anisotropy
      spectra.
AB  - An extensive spectroscopic study is presented of two asymmetrically substituted
      fluorene dyes and of the related spiro dimers in both liquid and glassy solvents.
      Essential-state models are developed to accurately reproduce linear absorption
      and fluorescence spectra and their complex dependence on solvent polarity. The
      same models are exploited to quantitatively calculate fluorescence excitation and
      anisotropy spectra in rigid matrixes. Impressive red-edge effects observed for
      spiro dimers in glassy polar solvents are accurately reproduced and understood.
      Interchromophore interactions in the spiro dimers are very small, leading to
      marginal effects in absorption and fluorescence spectra, but they effectively
      promote energy transfer between the two chromophores, as best evidenced comparing
      anisotropy spectra of the substituted fluorenes and of corresponding spiro dimers
      dissolved in glassy solvent matrixes.

PMID- 21870780
TI  - New SmCG phases in a hydrogen-bonded bent-core liquid crystal featuring a
      branched siloxane terminal group.
AB  - In this study, we synthesized three analogous bent-core molecules, a hydrogen
      bonded complex and a covalent-bonded compound with branched siloxane units (H-SiO
      and C-SiO, respectively) and a hydrogen-bonded complex with an alkyl unit (H
      Alk), and investigated the effects of the hydrogen bonding and branched siloxane
      terminal units on their mesomorphic properties. The covalent-bonded compound C
      SiO and the hydrogen-bonded complex H-Alk exhibited typical SmCP phases; in
      contrast, the hydrogen-bonded complex H-SiO exhibited a series of general tilt
      smectic (SmCG) phases with highly ordered layer structures (i.e., SmCG(2)P(F)
      USmCG(2)P(A)-SmCG(2)P(F)-SmCGP(F) upon cooling). During the SmCG-type phase
      transition process, a 2D-modulated ribbon structure transferred into highly
      ordered layers via undulated layers, as the hydrogen-bonding strength increased
      with reduced temperatures. As the SmCG domains were aligned under dc electric
      fields, a gradual decrease in the leaning angle from ca. 60 degrees  to 50
      degrees  (while the tilt angle kept at ca. 31 degrees ) could be determined by in
      situ wide-angle X-ray scattering (WAXS). Combined with Fourier transform infrared
      and Raman spectroscopic data, our results suggest that the change in the leaning
      angle was governed by the competition of the hydrogen bonds and microsegregation
      of siloxane units within the bilayer structure of the hydrogen-bonded complex H
      SiO. In addition, the ferroelectric-(antiferroelectric)-ferroelectric transitions
      proven by the switching current responses in the SmCG-type phases of H-SiO reveal
      that the polar switching occurred through collective rotations around the long
      axis of H-SiO. Therefore, novel SmCG phases with a series of highly ordered 2D
      structures were induced by the effects of the hydrogen bonding and branched
      terminal siloxane unit in the bent-core hydrogen-bonded LC complex H-SiO.

PMID- 21870781
TI  - Dynamics of ribavirin glass in the sub-Tg temperature region.
AB  - Fragility and the effect of annealing in the sub-T(g) temperature region on the
      characteristics of ribavirin glass were investigated using thermal analysis. The
      onset T(g) of ribavirin glass was determined to be 55.5  degrees C from modulated
      differential scanning calorimetry measurements under a heating rate of 2  degrees
      C/min. The ribavirin glass was proved as fragile from dynamic analysis using
      three evaluation methods and as very fragile from thermodynamic analysis based on
      the heat capacity difference between glassy and crystalline states. Enthalpy
      recovery was found for even freshly prepared ribavirin glass and was initiated
      far below T(g) in the thermal analysis, which suggested low cooperativity of the
      molecular motion. The width of the glass transition region was significantly
      narrowed, and T(g) was increased by sub-T(g) annealing at 40-45  degrees C,
      suggesting that a temperature region exists for the effective enhancement of
      molecular cooperativity. Quantification of the recovery enthalpy was conducted by
      integrating the thermal curve through a wide temperature range that included a
      baseline to determine the relaxation constants because peak integration, which is
      a frequently used procedure to determine recovery enthalpy, was not adequate due
      to significant alteration in the shape of the heat flow curves by annealing.
      Relaxation times obtained by the baseline integration procedure were larger than
      those from the conventional peak integration approach and exhibited better
      agreement with the Vogel-Tammann-Fulcher equation, revealing that this method may
      be notably beneficial for the evaluation of glasses with low molecular
      cooperativity. The size of the cooperative rearranging region (CRR) was
      determined from the width of the glass transition region and indicated the
      existence of an optimum temperature range to increase the size of the CRR just
      below T(g).

PMID- 21870782
TI  - What determines the activity of antimicrobial and cytolytic peptides in model
      membranes.
AB  - We previously proposed three hypotheses relating the mechanism of antimicrobial
      and cytolytic peptides in model membranes to the Gibbs free energies of binding
      and insertion into the membrane [Almeida, P. F., and Pokorny, A. (2009)
      Biochemistry 48, 8083-8093]. Two sets of peptides were designed to test those
      hypotheses, by mutating of the sequences of delta-lysin, cecropin A, and magainin
      2. Peptide binding and activity were measured on phosphatidylcholine membranes.
      In the first set, the peptide charge was changed by mutating basic to acidic
      residues or vice versa, but the amino acid sequence was not altered much
      otherwise. The type of dye release changed from graded to all-or-none according
      to prediction. However, location of charged residues in the sequence with the
      correct spacing to form salt bridges failed to improve binding. In the second
      set, the charged and other key residues were kept in the same positions, whereas
      most of the sequence was significantly but conservatively simplified, maintaining
      the same hydrophobicity and amphipathicity. This set behaved completely different
      from predicted. The type of release, which was expected to be maintained, changed
      dramatically from all-or-none to graded in the mutants of cecropin and magainin.
      Finally, contrary to the hypotheses, the results indicate that the Gibbs energy
      of binding to the membrane, not the Gibbs energy of insertion, is the primary
      determinant of peptide activity.

PMID- 21870783
TI  - Crystal structures of complexes with cobalt-reconstituted human arginase I.
AB  - The binuclear manganese metalloenzyme human arginase I (HAI) is a potential
      protein drug for cancer chemotherapy, in that it is capable of depleting
      extracellular l-Arg levels in the microenvironment of tumor cells that require
      this nutrient to thrive. Substitution of the native Mn(2+)(2) cluster with a
      Co(2+)(2) cluster in the active site yields an enzyme with enhanced catalytic
      activity at physiological pH (~7.4) that could serve as an improved protein drug
      for L-Arg depletion therapy [Stone, E. M., Glazer, E. S., Chantranupong, L.,
      Cherukuri, P., Breece, R. M., Tierney, D. L., Curley, S. A., Iverson, B. L., and
      Georgiou, G. (2010) ACS Chem. Biol. 5, 333-342]. A different catalytic mechanism
      is proposed for Co(2+)(2)-HAI compared with that of Mn(2+)(2)-HAI, including an
      unusual Nepsilon-Co(2+) coordination mode, to rationalize the lower K(M) value of
      L-Arg and the lower K(i) value of L-Orn. However, we now report that no unusual
      metal coordination modes are observed in the cobalt-reconstituted enzyme. The X
      ray crystal structures of unliganded Co(2+)(2)-HAI determined at 2.10 A
      resolution (pH 7.0) and 1.97 A resolution (pH 8.5), as well as the structures of
      Co(2+)(2)-HAI complexed with the reactive substrate analogue 2(S)-amino-6
      boronohexanoic acid (ABH, pH 7.0) and the catalytic product L-Orn (pH 7.0)
      determined at 1.85 and 1.50 A resolution, respectively, are essentially identical
      to the corresponding structures of Mn(2+)(2)-HAI. Therefore, in the absence of
      significant structural differences between Co(2+)(2)-HAI and Mn(2+)(2)-HAI, we
      suggest that a higher concentration of metal-bridging hydroxide ion at
      physiological pH for Co(2+)(2)-HAI, a consequence of the lower pK(a) of a Co(2+)
      bound water molecule compared with a Mn(2+)-bound water molecule, strengthens
      electrostatic interactions with cationic amino acids and accounts for enhanced
      affinity as reflected in the lower K(M) value of L-Arg and the lower K(i) value
      of L-Orn.

PMID- 21870784
TI  - Do some NO(x) emissions have negative environmental damages? Evidence and
      implications for policy.

PMID- 21870785
TI  - New ternary and quaternary barium nitride halides; synthesis and crystal
      chemistry.
AB  - New ternary and quaternary nitride halides, Ba(2)N(X,X') (X = F, Cl, Br; X' = Br,
      I), have been synthesized from the high temperature reactions of barium
      subnitride with the respective barium halides under an inert atmosphere. The
      former include the first fully characterized barium nitride halides for X other
      than F, and the latter are the first examples of barium nitride mixed halides.
      The variation in structure with composition has been investigated by powder X-ray
      and powder neutron diffraction techniques. The heavier ternary and quaternary
      nitride halides (X, X' = Cl, Br, I) crystallize in the hexagonal space group R3m,
      with the anti-alpha-NaFeO(2) structure. Ba(2)NF forms with both an anti-alpha
      NaFeO(2) structure, in which N(3-) and F(-) are ordered and an anion-disordered
      simple rock salt structure. The hexagonal polymorph of Ba(2)NF is the only
      example to date of a nitride fluoride adopting this layered structure. Both the
      ternary and the quaternary compounds display very weak, temperature independent
      paramagnetism.

PMID- 21870786
TI  - Synthesis and intramolecular hydrogen bonding networks of 2,4,6-tri(o
      hydroxyaryl)-1,3,5-triazines.
AB  - Functionalized, triaryl substituted triazines were synthesized via the Friedel
      Crafts arylation reaction. These conjugated triazines possess unique,
      intramolecular hydrogen bonding motifs, which provide tunable planarity.

PMID- 21870787
TI  - Alkoxyamine-derived formamidines: configurational control and molecular folding.
AB  - N,N'-Disubstituted formamidines, and amidines in general, have very rich
      configurational, conformational, and tautomeric diversities. As part of an effort
      to incorporate alkoxyamine-derived formamidine units into foldamers, the first
      evidence for the isolation of the up-to-now unknown E isomer, the conditions for
      its exclusive formation, its stability and self-assembly properties, and its
      configurational isomerization to its much more common Z counterpart are reported.
      Considering the distinctly different H-bonding patterns displayed by both E and Z
      isomers, such configurational control may find applications in self-assembly,
      molecular recognition, and biomimetic systems.

PMID- 21870788
TI  - New water-soluble organic capsules are effective in controlling excited-state
      processes of guest molecules.
AB  - Synthesis, inclusion properties, and ability to control excited-state properties
      of two water-soluble hosts are presented. These hosts surround the guest
      molecule(s) by forming a capsular assembly. By constraining the guest and by
      providing very little free space, the host is able to alter the excited-state
      behavior of guest molecules. The excited-state chemistry and physics of guest
      molecules are distinctly different from those in organic solvents.

PMID- 21870790
TI  - Calix[8]arene coated CdSe/ZnS quantum dots as C60-nanosensor.
AB  - Here, we report an optical sensor for fullerene C(60) in water using CdSe/ZnS
      quantum dots coated by p-tertbutylcalix[8]arene. This C(60)-nanosensor is based
      on the selective host-guest interaction between fullerene C(60) and p
      tertbutylcalix[8]arene. The procedure for the synthesis of p
      tertbutylcalix[8]arene-CdSe/ZnS complex is described, and its fluorescent
      characteristics are also reported. We found that the interaction between C(60)
      fullerene and p-tertbutylcalix[8]arene-CdSe/ZnS complex quenches the original
      fluorescence of calix-QDs according to the Stern-Volmer equation. The mechanism
      of interaction is discussed. Finally, the potential application of the proposed
      method using the designed nanosensor for determination of C(60) in spiked
      environmental river water samples is demonstrated. For the analysis of river
      samples, a liquid-liquid extraction multistep preconcentration procedure is
      proposed. The method, which is simple and rapid, allows the detection of 5 MUg L(
      1) of fullerene. This sensor could be a useful tool for environmental and
      toxicological studies.

PMID- 21870792
TI  - Chlorodifluoroacetyl cyanide, ClF2CC(O)CN: synthesis, structure, and
      spectroscopic characterization.
AB  - The novel molecule difluorochloroacetyl cyanide, ClF(2)CC(O)CN, has been
      characterized by IR (gas phase, Ar matrix), Raman (liquid), (19)F and (13)C NMR,
      and photoelectron (PES) spectroscopies; photoionization mass spectrometry (PIMS);
      and gas electron diffraction (GED). The conformational properties of
      ClF(2)CC(O)CN have been studied by joint application of vibrational spectroscopy,
      GED, and quantum chemical calculations. The existence of two conformers is
      detected in the gas and liquid phases, in which the C-Cl bond adopts gauche and
      syn orientations with respect to the C?O group. The computed enthalpy difference
      is in harmony with the experimental results of the gauche being more stable than
      the syn conformer by DeltaH degrees  = 1.3 kcal mol(-1) (MP2/cc-pVTZ). The
      valence electronic properties and the possible ionization and dissociation
      processes of the title compound are studied using the PES and PIMS. The
      experimental first vertical ionization energy of 12.0 eV corresponds to the
      ejection of an electron of the oxygen lone pairs. Taking into account the
      properties and broad applications of acyl cyanides, ClF(2)CC(O)CN is a promising
      new precursor in preparative chemistry.

PMID- 21870789
TI  - Exploration of possible binding sites of nanoparticles on protein by cross
      linking chemistry coupled with mass spectrometry.
AB  - For the first time, the possible binding site of nanoparticles on protein was
      revealed by cross-linking chemistry coupled with mass spectrometry. The peptides
      located very close to the poly(acrylic acid) (PAA)-coated Fe(3)O(4) nanoparticles
      (NPs) during interaction with human serum albumin (HSA) were cross-linked to the
      surface of NPs. Following protease digestion, the attached peptides were cleaved
      off the particle surface and identified by matrix-assisted laser
      desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). The
      peptides were found to be part of the so-called drug binding site 2 of HSA; and
      the competitive binding to HSA between the corresponding drug, ibuprofen, and the
      NPs was observed. Our results demonstrated that cross-linking chemistry coupled
      with MS was a quick and simple method for locating the possible binding sites of
      NPs on protein. Information on NP-protein binding interface will benefit the
      study of how the interactions are governed by the physicochemical properties of
      NPs, for guiding the design of functional bionano constructs. It can also help to
      predict the biological consequence of protein adsorption on NPs, for obtaining
      more knowledge on nanotoxicity.

PMID- 21870793
TI  - Picosecond dynamics of proton transfer of a 7-hydroxyflavylium salt in aqueous
      organic solvent mixtures.
AB  - The intermediacy of the geminate base-proton pair (A*...H(+)) in excited-state
      proton-transfer (ESPT) reactions (two-step mechanism) has been investigated
      employing the synthetic flavylium salt 7-hydroxy-4-methyl-flavylium chloride
      (HMF). In aqueous solution, the ESPT mechanism involves solely the excited acid
      AH(+)* and base A* forms of HMF as indicated by the fluorescence spectra and
      double-exponential fluorescence decays (two species, two decay times). However,
      upon addition of either 1,4-dioxane or 1,2-propylene glycol, the decays become
      triple-exponential with a term consistent with the presence of the geminate base
      proton pair A*...H(+). The geminate pair becomes detectable because of the
      increase in the recombination rate constant, k(rec), of (A*...H(+)) with
      increasing the mole fraction of added organic cosolvent. Because the two-step
      ESPT mechanism splits the intrinsic prototropic reaction rates (deprotonation of
      AH(+)*, k(d), and recombination, k(rec), of A*...H(+)) from the diffusion
      controlled rates (dissociation, k(diss), and formation, k(diff)[H(+)], of
      A*...H(+)), the experimental detection of the geminate pair provides a wealth of
      information on the proton-transfer reaction (k(d) and k(rec)) as well as on
      proton diffusion/migration (k(diss) and k(diff)).

PMID- 21870794
TI  - Immobilization, trapping, and anion exchange of perrhenate ion using copper-based
      tripodal complexes.
AB  - We describe a multidentate tripodal ligand in which three pendant arms carrying
      di(2-picolyl)amine units are linked to the ortho positions of a tris(o-xylyl)
      scaffold, providing N(CH(2)-o-C(6)H(4)CH(2)N(CH(2)py)(2))(3) (L). Reaction of L
      with CuCl(2) in the presence of hexafluorophosphate anion afforded blue cubes of
      [(CuCl)(3)L](PF(6))(3).5H(2)O (1). Crystallographic studies of 1 revealed that
      the three symmetry-related arms each coordinate a {Cu(II)Cl} unit, and two
      molecules of 1 are connected to one another through a Cu(MU-Cl)(2)Cu bridge,
      extending the molecular structure to form a two-dimensional (2-D) layer. These 2
      D layers pack in an ABCABC... fashion with PF(6)(-) anions located in between.
      Reaction of 1 with a stoichiometric amount of perrhenate ion afforded blue plates
      of [(CuCl)(3)L](PF(6))(ReO(4))(2).3H(2)O (2). Compound 2 has the same lattice
      structure as 1, but the tricopper unit backbone now traps one ReO(4)(-) anion
      through Coulombic interactions. In addition, three molecules of 2 are bridged by
      a perrhenate ion, forming a Cu(3)(MU(3)-ReO(4)) cluster, to give a different 2-D
      structure displaying a rare tridentate bridging ReO(4)(-) mode. Thus, in addition
      to classic perrhenate trapping through weak Coulombic interactions, 2 represents
      an exceptional example in which the ReO(4)(-) anion is immobilized in an extended
      framework through tight covalent interactions. The interlamellar PF(6)(-) anions
      in 1 can be exchanged with other anions including perrhenate, perchlorate, or
      periodate. The structural similarity between perrhenate and pertechnetate makes
      these materials of potential interest for pertechnetate trapping.

PMID- 21870796
TI  - Catalytic intermolecular hetero-dehydro-Diels-Alder cycloadditions: regio- and
      diasteroselective synthesis of 5,6-dihydropyridin-2-ones.
AB  - A novel catalyzed intermolecular heterodehydro-Diels-Alder reaction between push
      pull 1,3-dien-5-ynes and aldimines or silylaldimines is reported. The sequence is
      promoted both by gold(I) or silver(I) catalysts and leads to the diastereo- and
      regioselective formation of 5,6-dihydropyridin-2-ones.

PMID- 21870797
TI  - Surface modification of silicate glass using 3-(mercaptopropyl)trimethoxysilane
      for thiol-ene polymerization.
AB  - A thiol-ene polymerization was accomplished on silicate glass slides to graft a
      series of homopolymers and copolymers using 3-(mercaptopropyl)trimethoxysilane
      (MTS) as both a silane coupling agent and initiator. MTS was initially covalently
      bonded to an acid cleaned glass surface via a classical sol-gel reaction.
      Poly(acrylic acid) (PAA), poly(acrylamide) (PAAm), poly(methyl acrylate) (PMA),
      poly(acrylamido-2-methyl-propanesulfonic acid) (PAMPS), and the copolymer poly(AA
      co-AAm-co-MA-co-AMPS) were grafted from the thiol group of MTS. The surface
      chemistry of the MTS modified slides and polymer grafts was characterized with
      attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy
      and X-ray photoelectron spectroscopy (XPS). Surface texture was evaluated with
      tapping mode atomic force microscopy (TM-AFM). The Owens-Wendt-Kaelble (OWK) and
      Lifshitz-van der Waals acid-base (LW-AB) methods were used to evaluate surface
      energies by sessile drop contact angle method. The synthetic approach
      demonstrated a facile, rapid method for grafting to glass surfaces.

PMID- 21870795
TI  - Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced
      biological activity.
AB  - Potential binding modes of (+)-discodermolide at the paclitaxel binding site of
      tubulin have been identified by computational studies based on earlier structural
      and SAR data. Examination of the prospective binding modes reveal that the
      aromatic pocket occupied by the paclitaxel side chain is unoccupied by (+)
      discodermolide. Based on these findings, a small library of (+)-discodermolide
      paclitaxel hybrids have been designed and synthesized. Biological evaluation
      reveals a two- to eight-fold increase in antiproliferative activity compared to
      the parent molecule using the A549 and MCF-7 cancer cell lines.

PMID- 21870798
TI  - Study of the adsorption reactions of thiophene on Cu(I)/HY-Al2O3 by Fourier
      transform infrared and temperature-programmed desorption: adsorption, desorption,
      and sorbent regeneration mechanisms.
AB  - This work mainly involved the investigation of the adsorption of thiophene on
      Cu(I)-supported HY-Al(2)O(3). It demonstrated a high sulfur capacity of 10 mg
      sulfur/g sorbent when the HY/Al(2)O(3) mass ratio was 3, loaded with 12% copper,
      calcined at 550  degrees C, and tested at ambient temperature. In situ Fourier
      transform infrared (FTIR) and temperature-programmed desorption (TPD) results
      indicated that the adsorption mechanisms on Cu(I)/HY-Al(2)O(3) primarily were pi
      complexation and sulfur-adsorbent (S-M; sigma) bonds. Pyridine-FTIR showed the
      total weak Lewis acid contribution to the Cu(I)/HY-Al(2)O(3) adsorption
      desulfurization performance.

PMID- 21870799
TI  - The impact of metallic coagulants on the removal of organic compounds from oil
      sands process-affected water.
AB  - Coagulation/flocculation (CF) by use of alum and cationic polymer polyDADMAC, was
      performed as a pretreatment for remediation of oil sands process-affected water
      (OSPW). Various factors were investigated and the process was optimized to
      improve efficiency of removal of organic carbon and turbidity. Destabilization of
      the particles occurred through charge neutralization by adsorption of hydroxide
      precipitates. Scanning electron microscope images revealed that the resultant
      flocs were compact. The CF process significantly reduced concentrations of
      naphthenic acids (NAs) and oxidized NAs by 37 and 86%, respectively,
      demonstrating the applicability of CF pretreatment to remove a persistent and
      toxic organic fraction from OSPW. Concentrations of vanadium and barium were
      decreased by 67-78% and 42-63%, respectively. Analysis of surface functional
      groups on flocs also confirmed the removal of the NAs compounds. Flocculation
      with cationic polymer compared to alum, caused toxicity toward the benthic
      invertebrate, Chironoums dilutus, thus application of the polymer should be
      limited.

PMID- 21870801
TI  - Backtracking of colloids: a multiparticle collision dynamics simulation study.
AB  - The role of sound in the dynamics of mesoscale systems is typically neglected,
      since frequently the associated time scales are much smaller than all the other
      time scales of interest. However, for sufficiently small objects embedded in a
      solvent with a sufficiently small sound velocity, sound can play a crucial role.
      In particular, behavior resembling viscoelasticity has been theoretically
      predicted for nonviscoelastic fluids. This effect is due to the interference of
      the propagation of sound waves caused by the solute particle's motion and
      hydrodynamic vortex formation. We demonstrate this effect, known as backtracking,
      in computer simulations employing the method of multiparticle collision dynamics.
      We systematically study the influence of sound on the dynamics of the solute
      particle, and find that it disappears in the long-time limit. Thus, we confirm
      that sonic effects at the single-particle level can be neglected at sufficiently
      long times.

PMID- 21870802
TI  - Qualitative analysis of tackifier resins in pressure sensitive adhesives using
      direct analysis in real time time-of-flight mass spectrometry.
AB  - Tackifier resins play an important role as additives in pressure sensitive
      adhesives (PSAs) to modulate their desired properties. With dependence on their
      origin and processing, tackifier resins can be multicomponent mixtures. Once they
      have been incorporated in a polymer matrix, conventional chemical analysis of
      tackifiers usually tends to be challenging because a suitable sample pretreatment
      and/or separation is necessary and all characteristic components have to be
      detected for an unequivocal identification of the resin additive. Nevertheless, a
      reliable analysis of tackifiers is essential for product quality and safety
      reasons. A promising approach for the examination of tackifier resins in PSAs is
      the novel direct analysis in real time mass spectrometry (DART-MS) technique,
      which enables screening analysis without time-consuming sample preparation. In
      the present work, four key classes of tackifier resins were studied (rosin,
      terpene phenolic, polyterpene, and hydrocarbon resins). Their corresponding
      complex mass spectra were interpreted and used as reference spectra for
      subsequent analyses. These data were used to analyze tackifier additives in
      synthetic rubber and acrylic adhesive matrixes. To prove the efficiency of the
      developed method, complete PSA products containing two or three different
      tackifiers were analyzed. The tackifier resins were successfully identified,
      while measurement time and interpretation took less than 10 mins per sample.
      Determination of resin additives in PSAs can be performed down to 0.1% (w/w,
      limit of detection) using the three most abundant signals for each tackifier. In
      summary, DART-MS is a rapid and efficient screening method for the analysis of
      various tackifiers in PSAs.

PMID- 21870803
TI  - Adaptive supramolecular nanomaterials based on strong noncovalent interactions.
AB  - Noncovalent systems are adaptive and allow facile processing and recycling. Can
      they be at the same time robust? How can one rationally design such systems? Can
      they compete with high-performance covalent materials? The recent literature
      reveals that noncovalent systems can be robust yet adaptive, self-healing, and
      recyclable, featuring complex nanoscale structures and unique functions. We
      review such systems, focusing on the rational design of strong noncovalent
      interactions, kinetically controlled pathway-dependent processes, complexity, and
      function. The overview of the recent examples points at the emergent field of
      noncovalent nanomaterials that can represent a versatile, multifunctional, and
      environmentally friendly alternative to conventional covalent systems.

PMID- 21870804
TI  - Theory of nonrigid rotational motion applied to NMR relaxation in RNA.
AB  - Solution NMR spectroscopy can elucidate many features of the structure and
      dynamics of macromolecules, yet relaxation measurements, the most common source
      of experimental information on dynamics, can sample only certain ranges of
      dynamic rates. A complete characterization of motion of a macromolecule thus
      requires the introduction of complementary experimental approaches. Solid-state
      NMR spectroscopy successfully probes the time scale of nanoseconds to
      microseconds, a dynamic window where solution NMR results have been deficient,
      and probes conditions where the averaging effects of rotational diffusion of the
      molecule are absent. Combining the results of the two distinct techniques within
      a single framework provides greater insight into dynamics, but this task requires
      the common interpretation of results recorded under very different experimental
      conditions. Herein, we provide a unified description of dynamics that is robust
      to the presence of large-scale conformational exchange, where the diffusion
      tensor of the molecule varies on a time scale comparable to rotational diffusion
      in solution. We apply this methodology to the HIV-1 TAR RNA molecule, where
      conformational rearrangements are both substantial and functionally important.
      The formalism described herein is of greater generality than earlier combined
      solid-state/solution NMR interpretations, if detailed molecular structures are
      available, and can offer a more complete description of RNA dynamics than either
      solution or solid-state NMR spectroscopy alone.

PMID- 21870805
TI  - Substrate specificity of Sphingobium chlorophenolicum 2,6-dichlorohydroquinone
      1,2-dioxygenase.
AB  - PcpA is an aromatic ring-cleaving dioxygenase that is homologous to the well
      characterized Fe(II)-dependent catechol extradiol dioxygenases. This enzyme
      catalyzes the oxidative cleavage of 2,6-dichlorohydroquinone in the catabolism of
      pentachlorophenol by Sphingobium chlorophenolicum ATCC 39723. (1)H NMR and steady
      state kinetics were used to determine the regiospecificity of ring cleavage and
      the substrate specificity of the enzyme. PcpA exhibits a high degree of substrate
      specificity for 2,6-disubstituted hydroquinones, with halogens greatly preferred
      at those positions. Notably, the k(cat)(app)/K(mA)(app) of 2,6
      dichlorohydroquinone is ~40-fold higher than that of 2,6-dimethylhydroquinone.
      The asymmetric substrate 2-chloro-6-methylhydroquinone yields a mixture of 1,2-
      and 1,6-cleavage products. These two modes of cleavage have different
      K(mO(2))(app) values (21 and 260 MUM, respectively), consistent with a mechanism
      in which the substrate binds in two catalytically productive orientations. In
      contrast, monosubstituted hydroquinones show a limited amount of ring cleavage
      but rapidly inactivate the enzyme in an O(2)-dependent fashion, suggesting that
      oxidation of the Fe(II) may be the cause. Potent inhibitors of PcpA include ortho
      disubstituted phenols and 3-bromocatechol. 2,6-Dibromophenol is the strongest
      competitive inhibitor, consistent with PcpA's substrate specificity. Several
      factors that could yield this specificity for halogen substituents are discussed.
      Interestingly, 3-bromocatechol also inactivates the enzyme, while 2,6
      dihalophenols do not, indicating a requirement for two hydroxyl groups for ring
      cleavage and for enzyme inactivation. These results provide mechanistic insights
      into the hydroquinone dioxygenases.

PMID- 21870806
TI  - Matrix infrared spectroscopic and theoretical studies on the reactions of
      scandium, yttrium, and lanthanide metal atoms with dimethyl ether.
AB  - Reactions of laser-ablated scandium, yttrium, lanthanum, and several lanthanide
      metal atoms with dimethyl ether have been studied using matrix isolation infrared
      spectroscopy. Identifications of the major products, M(CH(3)OCH(3)) and
      CH(3)OMCH(3) (M = Sc, Y, La, Ce, Gd, Tb, Yb, and Lu), are supported by
      experiments with deuterium substitution as well as theoretical calculations. It
      is found that most ground-state metal atoms react with dimethyl ether to give the
      M(CH(3)OCH(3)) complexes spontaneously on annealing, which isomerize to the
      CH(3)OMCH(3) insertion products with visible irradiation. Density functional
      calculations reveal that the M(CH(3)OCH(3)) complexes possess C(2v) symmetry with
      metal atoms bound to the oxygen side of dimethyl ether, and bent geometries are
      found for the inserted CH(3)OMCH(3) molecules with direct M-O and C-O bonds. All
      of these products have the same ground states as their corresponding metal atoms
      except for Tb. Although the Lu(CH(3)OCH(3)) complex is predicted to be a stable
      molecule, it is not observed in the experiment due to the low energy barrier for
      the subsequent C-O bond insertion reaction.

PMID- 21870807
TI  - Low pH acts as inhibitor of membrane damage induced by human islet amyloid
      polypeptide.
AB  - Human islet amyloid polypeptide (IAPP) is the major component of the amyloid
      deposits found in the pancreatic islets of patients with type 2 diabetes
      mellitus. After synthesis, IAPP is stored in the beta-cell granules of the
      pancreas at a pH of approximately 5.5 and released into the extracellular
      compartment at a pH of 7.4. To gain insight into the possible consequences of pH
      differences for properties and membrane interaction of IAPP, we here compared the
      aggregational and conformational behavior of IAPP as well as IAPP-membrane
      interactions at pH 5.5 and pH 7.4. Our data reveal that a low pH decreases the
      rate of fibril formation both in solution and in the presence of membranes. We
      observed by CD spectroscopy that these differences in kinetics are directly
      linked to changes in the conformational behavior of the peptide. Mechanistically,
      the processes that occur at pH 5.5 and pH 7.4 appear to be similar. At both pH
      values, we found that the kinetic profile of IAPP fibril growth matches the
      kinetic profile of IAPP-induced membrane damage, and that both are characterized
      by a lag phase and a sigmoidal transition. Furthermore, monolayer studies as well
      as solid-state NMR experiments indicate that the differences in kinetics and
      conformational behavior as function of pH are not due to a different mode of
      membrane insertion. Our study suggests that a low pH prevents aggregation and
      membrane damage of IAPP in the secretory granules, most likely by affecting the
      ionization properties of the peptide.

PMID- 21870809
TI  - Substrate binding modulates the activity of Mycobacterium smegmatis G, a flavin
      dependent monooxygenase involved in the biosynthesis of hydroxamate-containing
      siderophores.
AB  - Mycobacterium smegmatis G (MbsG) is a flavin-dependent monooxygenase that
      catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of the terminal amino
      group on the side chain of l-lysine in the biosynthetic pathway of the
      siderophore mycobactin. Mycobactins are essential for mycobacterium growth under
      iron-limiting conditions encountered during infection in mammals. Thus, enzymes
      involved in the biosynthesis of mycobactin represent potential drug targets. MbsG
      was expressed in Escherichia coli and purified using metal affinity and ionic
      exchange chromatographies. Recombinant MbsG represents the first member of this
      class of enzymes isolated in the active form, with a tightly bound FAD cofactor.
      The k(cat) value for formation of hydroxylated l-lysine under steady-state
      conditions was 5.0 min(-1), and K(m) values of 0.21 mM for l-lysine, 1.1 mM for
      NADH, and 2.4 mM for NADPH were calculated. The enzyme functioned as an oxidase
      when the activity of MbsG was measured by monitoring oxygen consumption in the
      absence of l-lysine, oxidizing NADH and NADPH with k(cat) values of 59 and 49
      min(-1), respectively. Under these conditions, MbsG produced both hydrogen
      peroxide and superoxide. In contrast, when l-lysine was present, the reaction
      became more coupled, producing hydroxylated l-lysine and decreasing the oxidase
      activity. These results suggest that substrate binding modulates the function of
      MbsG from an oxidase to a monooxygenase.

PMID- 21870808
TI  - Spectroscopic and computational studies of alpha-keto acid binding to Dke1:
      understanding the role of the facial triad and the reactivity of beta-diketones.
AB  - The O(2) activating mononuclear nonheme iron enzymes generally have a common
      facial triad (two histidine and one carboxylate (Asp or Glu) residue) ligating
      Fe(II) at the active site. Exceptions to this motif have recently been identified
      in nonheme enzymes, including a 3His triad in the diketone cleaving dioxygenase
      Dke1. This enzyme is used to explore the role of the facial triad in directing
      reactivity. A combination of spectroscopic studies (UV-vis absorption, MCD, and
      resonance Raman) and DFT calculations is used to define the nature of the binding
      of the alpha-keto acid, 4-hydroxyphenlpyruvate (HPP), to the active site in Dke1
      and the origin of the atypical cleavage (C2-C3 instead of C1-C2) pattern
      exhibited by this enzyme in the reaction of alpha-keto acids with dioxygen. The
      reduced charge of the 3His triad induces alpha-keto acid binding as the enolate
      dianion, rather than the keto monoanion, found for alpha-keto acid binding to the
      2His/1 carboxylate facial triad enzymes. The mechanistic insight from the
      reactivity of Dke1 with the alpha-keto acid substrate is then extended to
      understand the reaction mechanism of this enzyme with its native substrate, acac.
      This study defines a key role for the 2His/1 carboxylate facial triad in alpha
      keto acid-dependent mononuclear nonheme iron enzymes in stabilizing the bound
      alpha-keto acid as a monoanion for its decarboxylation to provide the two
      additional electrons required for O(2) activation.

PMID- 21870810
TI  - Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction:
      importance of residues in the orotate binding site.
AB  - The reaction catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) is
      accompanied by exceptional values for rate enhancement (k(cat)/k(non) = 7.1 *
      10(16)) and catalytic proficiency [(k(cat)/K(M))/k(non) = 4.8 * 10(22) M(-1)].
      Although a stabilized vinyl carbanion/carbene intermediate is located on the
      reaction coordinate, the structural strategies by which the reduction in the
      activation energy barrier is realized remain incompletely understood. This
      laboratory recently reported that "substrate destabilization" by Asp 70 in the
      OMPDC from Methanothermobacter thermoautotrophicus (MtOMPDC) lowers the
      activation energy barrier by ~5 kcal/mol (contributing ~2.7 * 10(3) to the rate
      enhancement) [Chan, K. K., Wood, B. M., Fedorov, A. A., Fedorov, E. V., Imker, H.
      J., Amyes, T. L., Richard, J. P., Almo, S. C., and Gerlt, J. A. (2009)
      Biochemistry 48, 5518-5531]. We now report that substitutions of hydrophobic
      residues in a pocket proximal to the carboxylate group of the substrate (Ile 96,
      Leu 123, and Val 155) with neutral hydrophilic residues decrease the value of
      k(cat) by as much as 400-fold but have a minimal effect on the value of k(ex) for
      exchange of H6 of the FUMP product analogue with solvent deuterium; we
      hypothesize that this pocket destabilizes the substrate by preventing hydration
      of the substrate carboxylate group. We also report that substitutions of Ser 127
      that is proximal to O4 of the orotate ring decrease the value of k(cat)/K(M),
      with the S127P substitution that eliminates hydrogen bonding interactions with O4
      producing a 2.5 * 10(6)-fold reduction; this effect is consistent with
      delocalization of the negative charge of the carbanionic intermediate on O4 that
      produces an anionic carbene intermediate and thereby provides a structural
      strategy for stabilization of the intermediate. These observations provide
      additional information about the identities of the active site residues that
      contribute to the rate enhancement and, therefore, insights into the structural
      strategies for catalysis.

PMID- 21870811
TI  - Site-specific fluorescent labeling of nascent proteins on the translating
      ribosome.
AB  - As newly synthesized proteins emerge from the ribosome, they interact with a
      variety of cotranslational cellular machineries that facilitate their proper
      folding, maturation, and localization. These interactions are essential for
      proper function of the cell, and the ability to study these events is crucial to
      understanding cellular protein biogenesis. To this end, we have developed a
      highly efficient method to generate ribosome-nascent chain complexes (RNCs) site
      specifically labeled with a fluorescent dye on the nascent polypeptide. The
      fluorescent RNC provides real-time, quantitative information on its
      cotranslational interaction with the signal recognition particle and will be a
      valuable tool in elucidating the role of the translating ribosome in numerous
      biochemical pathways.

PMID- 21870812
TI  - Superhydrophobic fiber mats by electrodeposition of fluorinated poly(3,4
      ethyleneoxythiathiophene).
AB  - The control of surface morphology and wettability is crucial in the development
      of superhydrophobic surfaces, which implies new strategy and molecular design. In
      this Article, we report the synthesis, characterization, and electrochemical
      properties of original 3,4-ethyleneoxythiathiophenes (EOTT) as platform molecules
      and its derivatives bearing a semifluorinated chain of various length (F-octyl, F
      hexyl, F-butyl, and F-ethyl). We report the influence of the fluorinated chain
      length as well as the presence of sulfur atoms in the monomer on the surface
      construction and nonwetting properties of the corresponding electrodeposited
      polymer films. Surprisingly, these films exhibit the possibility to obtain
      extremely long polymer fibers with a possible control of their length by a
      careful choice in the monomer structure. We show that the presence of sulfur
      atoms in the monomer structure seems to be necessary to modulate the formation of
      extremely long polymer fibers by aggregation of smaller polymer fibrils. In this
      Article, the formation of superhydrophobic material (contact angle above 150
      degrees ) for four, six, and eight fluoromethylene units but also highly
      hydrophobic surfaces (contact angle above 125 degrees ) from extremely short
      chains (two fluoromethylene units) is also demonstrated.

PMID- 21870814
TI  - Protonation of lipids impacts the supramolecular and biological properties of
      their self-assembly.
AB  - We assessed in this work how a chemical structure difference could influence a
      supramolecular organization and then its biological properties. In our case
      study, we considered two amphiphilic lipidic gene vectors. The chemical
      difference was situated on their hydrophilic part which was either a pure neutral
      thiourea head or a mixture of three thiourea function derivatives, thiourea,
      iminothiol, and charged iminothiol. This small difference was obtained thanks to
      the last chemical deprotection conditions of the polar head hydroxyl groups.
      Light, neutron, and X-ray scattering techniques have been used to investigate the
      spatial structure of the liposomes and lipoplexes formed by the lipids. The
      chemical structure difference impacts the supramolecular assemblies of the lipids
      and with DNA as shown by fluorescence correlation spectroscopy (FCS), X-ray, and
      neutron scattering. Hence the structures formed were found to be highly different
      in terms of liposomes to DNA ratio and size and polydispersity of the aggregates.
      Finally, the transfection and internalization results proved that the differences
      in the structure of the lipid aggregates fully affect the biological properties
      of the lipopolythiourea compounds. The lipid containing three functions is a
      better gene transfection agent than the lipid which only contains one thiourea
      moiety. As a conclusion, we showed that the conditions of the last chemical step
      can influence the lipidic supramolecular structure which in turn strongly impacts
      their biological properties.

PMID- 21870813
TI  - Recent advances in nonviral vectors for gene delivery.
AB  - Gene therapy has long been regarded a promising treatment for many diseases,
      whether acquired (such as AIDS or cancer) or inherited through a genetic
      disorder. A drug based on a nucleic acid, however, must be delivered to the
      interior of the target cell while surviving an array of biological defenses honed
      by evolution. Successful gene therapy is thus dependent on the development of an
      efficient delivery vector. Researchers have pursued two major vehicles for gene
      delivery: viral and nonviral (synthetic) vectors. Although viral vectors
      currently offer greater efficiency, nonviral vectors, which are typically based
      on cationic lipids or polymers, are preferred because of safety concerns with
      viral vectors. So far, nonviral vectors can readily transfect cells in culture,
      but efficient nanomedicines remain far removed from the clinic. Overcoming the
      obstacles associated with nonviral vectors to improve the delivery efficiency and
      therapeutic effect of nucleic acids is thus an active area of current research.
      The difficulties are manifold, including the strong interaction of cationic
      delivery vehicles with blood components, uptake by the reticuloendothelial system
      (RES), toxicity, and managing the targeting ability of the carriers with respect
      to the cells of interest. Modifying the surface with poly(ethylene glycol), that
      is, PEGylation, is the predominant method used to reduce the binding of plasma
      proteins to nonviral vectors and minimize clearance by the RES after intravenous
      administration. Nanoparticles that are not rapidly cleared from the circulation
      accumulate in the tumors because of the enhanced permeability and retention
      effect, and the targeting ligands attached to the distal end of the PEGylated
      components allow binding to the receptors on the target cell surface. Neutral and
      anionic liposomes have been also developed for systemic delivery of nucleic acids
      in experimental animal models. Other approaches include (i) designing and
      synthesizing novel cationic lipids and polymers, (ii) chemically coupling the
      nucleic acid to peptides, targeting ligands, polymers, or environmentally
      sensitive moieties, and (iii) utilizing inorganic nanoparticles in nucleic acid
      delivery. Recently, the different classes of nonviral vectors appear to be
      converging, and the ability to combine features of different classes of nonviral
      vectors in a single strategy has emerged. With the strengths of several
      approaches working in concert, more hurdles associated with efficient nucleic
      acid delivery might therefore be overcome. In this Account, we focus on these
      novel nonviral vectors, which are classified as multifunctional hybrid nucleic
      acid vectors, novel membrane/core nanoparticles for nucleic acid delivery, and
      ultrasound-responsive nucleic acid vectors. We highlight systemic delivery
      studies and consider the future prospects for nucleic acid delivery. A better
      understanding of the fate of the nanoparticles inside the cell and of the
      interactions between the parts of hybrid particles should lead to a delivery
      system suitable for clinical use. We also underscore the value of sustained
      release of a nucleic acid in this endeavor; making vectors targeted to cells with
      sustained release in vivo should provide an interesting research challenge.

PMID- 21870815
TI  - Photochemical two-electron reduction of a dinuclear ruthenium complex containing
      a bent tetraazatetrapyridopentacene bridging ligand: pushing up the LUMO for
      storing more energy.
AB  - The synthesis and characterization of a ditopic bridging ligand, 9,12,21,22
      tetraazatetrapyrido[3,2-a:2',3'-c:3"2"-m:2''',3'''-o]pentaphene (tatppalpha) and
      its dinuclear ruthenium complex, [(phen)(2)Ru(tatppalpha)Ru(phen)(2)][PF(6)](4)
      (1(4+)), are described. The tatppalpha ligand is structurally very similar to
      9,10,20,33-tetraazatetrapyrido[3,2-a:2',3'-c:3",2"-l:2''',3'''-n]pentacene
      (tatppbeta), except that, instead of a linear tetraazapentacene backbone,
      tatppalpha has an ortho (or alpha) substitution pattern about the central benzene
      ring, leading to a 120 degrees  bend. Complex 1(4+) shows tatppalpha-based
      reductions at -0.73 and -1.14 V vs Ag/AgCl/saturated KCl and has an absorption
      spectrum showing the typical Ru(II) dpi -> phen-like pi* metal-to-ligand charge
      transfer transition centered at ~450 nm. In acetonitrile, visible-light
      irradiation of 1(4+) in the presence of triethylamine leads to two sequential
      changes in the absorption spectra, which are assigned to the formation of the one
      and two-electron-reduced species, with the electrons stored on the tatppalpha
      ligand. These assignments were made by comparison of the spectral changes
      observed in 1(4+) upon stoichiometric chemical reduction with cobaltocene and by
      spectroelectrochemical analysis. Significantly, DFT calculations are very
      predictive of the optical and reductive behavior of the tatppalpha complex
      relative to the tatppbeta complexes and show that modeling is a useful tool for
      ligand design. The chemical reactivity and differential reflectance
      spectroelectrochemical data reveal that the reductions are accompanied by radical
      dimerization of the tatppalpha ligand to species such as sigma-{1}(2)(6+), which
      is only slowly reversible upon exposure to air and may limit the complexe's 1(4+)
      utility for driving photochemical H(2) production.

PMID- 21870816
TI  - Rationalization of the lanthanide-ion-driven magnetic properties in a series of
      4f-5d cyano-bridged chains.
AB  - Magnetic properties of new d-f cyanido-bridged 1D assemblies
      [RE(pzam)(3)(H(2)O)W(CN)(8)].H(2)O (RE(III) = Gd, 1, Tb, 2, Dy, 3; pzam =
      pyrazine-2-carboxamide) were studied by temperature- and field-dependent
      magnetization measurements. No evidence for 3D interchain magnetic ordering is
      found above 2 K. Multiconfiguration ab initio calculations and subsequent
      modeling afforded simulation of the weak zero-field splitting effect in 1 and
      discussion of magnetic anisotropy in the f units of compounds 2 and 3. A
      semiquantitative corroboration with the experimental magnetic measurements is
      presented, performing the simulation of magnetic susceptibility vs temperature
      and magnetization vs field variation. The association into molecular and
      supramolecular architectures is analyzed by means of energy decomposition
      subsequent to the DFT calculations on idealized molecular models extracted from
      the experimental chain structure.

PMID- 21870817
TI  - Novel multiresponsive microgels: synthesis and characterization studies.
AB  - The dispersion polymerization of 2-(N-morpholino)ethyl methacrylate (MEMA) in the
      presence of ethylene glycol dimethylacrylate (EGDMA) cross-linker and diblock
      copolymer stabilizer in n-hexane afforded sterically stabilized multiresponsive
      PMEMA microgels. By changing the reaction parameters, a wide range of particle
      sizes (120-720 nm) was obtained. Both dynamic light scattering and electron
      microscopy studies confirmed monodisperse spherical morphologies. These microgels
      had a response to the solution pH, temperature, and ionic strength. As expected,
      PMEMA microgels acquired cationic character at low pH because of the protonation
      of all morpholino groups. Although PMEMA microgels are in a swollen state in both
      acidic media and at low temperatures, they are in a deswollen state in basic
      media at high temperatures and in the presence of electrolytes above pH 6. In
      addition to these multiresponsive behaviors, PMEMA microgels have the ability to
      swell in various organic solvents. They also interact very well with magnetic
      particles and gain responsiveness to the magnetic field. Multiresponsive
      behaviors of PMEMA microgels were investigated by using DLS, UV-vis
      spectrophotometry, and zeta potentiometry.

PMID- 21870818
TI  - Unprecedented selectivity and structural determinants of a new class of protein
      kinase CK2 inhibitors in clinical trials for the treatment of cancer.
AB  - 5-(3-Chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945),
      the first clinical stage inhibitor of protein kinase CK2 for the treatment of
      cancer, is representative of a new class of CK2 inhibitors with K(i) values in
      the low nanomolar range and unprecedented selectivity versus other kinases. Here
      we present the crystal structure of the complexes of CX-4945 and two analogues
      (CX-5011 and CX-5279) with the catalytic subunit of human CK2. Consistent with
      their ATP-competitive mode of inhibition, all three compounds bind in the active
      site of CK2 (type I inhibitors). The tricyclic scaffold of the inhibitors
      superposes on the adenine of ATP, establishing multiple hydrophobic interactions
      with the binding cavity. The more extended scaffold, as compared to that of ATP,
      allows the carboxylic function, shared by all three ligands, to penetrate into
      the deepest part of the active site where it makes interactions with conserved
      water W1 and Lys-68, thus accounting for the crucial role of this negatively
      charged group in conferring high potency to this class of inhibitors. The
      presence of a pyrimidine in CX-5011 and in CX-5279 instead of a pyridine (as in
      CX-4945) ring is likely to account for the higher specificity of these compounds
      whose Gini coefficients, calculated by profiling them against panels of 102
      and/or 235 kinases, are significantly higher than that of CX-4945 (0.735 and
      0.755, respectively, vs 0.615), marking the highest selectivity ever reported for
      CK2 inhibitors.

PMID- 21870819
TI  - Structural basis of the substrate specificity of bifunctional isocitrate
      dehydrogenase kinase/phosphatase.
AB  - Isocitrate dehydrogenase kinase/phosphatase (AceK) regulates entry into the
      glyoxylate bypass by reversibly phosphorylating isocitrate dehydrogenase (ICDH).
      On the basis of the recently determined structure of the AceK-ICDH complex from
      Escherichia coli, we have classified the structures of homodimeric NADP(+)-ICDHs
      to rationalize and predict which organisms likely contain substrates for AceK.
      One example is Burkholderia pseudomallei (Bp). Here we report a crystal structure
      of Bp-ICDH that exhibits the necessary structural elements required for AceK
      recognition. Kinetic analyses provided further confirmation that Bp-ICDH is a
      substrate for AceK. We conclude that the highly stringent AceK binding sites on
      ICDH are maintained only in Gram-negative bacteria.

PMID- 21870820
TI  - Allosteric activation via kinetic control: potassium accelerates a conformational
      change in IMP dehydrogenase.
AB  - Allosteric activators are generally believed to shift the equilibrium
      distribution of enzyme conformations to favor a catalytically productive
      structure; the kinetics of conformational exchange is seldom addressed. Several
      observations suggested that the usual allosteric mechanism might not apply to the
      activation of IMP dehydrogenase (IMPDH) by monovalent cations. Therefore, we
      investigated the mechanism of K(+) activation in IMPDH by delineating the kinetic
      mechanism in the absence of monovalent cations. Surprisingly, the K(+) dependence
      of k(cat) derives from the rate of flap closure, which increases by >=65-fold in
      the presence of K(+). We performed both alchemical free energy simulations and
      potential of mean force calculations using the orthogonal space random walk
      strategy to computationally analyze how K(+) accelerates this conformational
      change. The simulations recapitulate the preference of IMPDH for K(+), validating
      the computational models. When K(+) is replaced with a dummy ion, the residues of
      the K(+) binding site relax into ordered secondary structure, creating a barrier
      to conformational exchange. K(+) mobilizes these residues by providing alternate
      interactions for the main chain carbonyls. Potential of mean force calculations
      indicate that K(+) changes the shape of the energy well, shrinking the reaction
      coordinate by shifting the closed conformation toward the open state. This work
      suggests that allosteric regulation can be under kinetic as well as thermodynamic
      control.

PMID- 21870822
TI  - 2-(3,5-Dinitrophenyl)-1,3-dithiane carbanion: a benzylic anion with a low energy
      triplet state.
AB  - Calculations at the DFT level predict that benzyl anions with strong pi-electron
      withdrawing groups in the meta position(s) have low energy diradical or triplet
      electronic states. Specifically, the 2-(3,5-dinitrophenyl)-1,3-dithiane carbanion
      is predicted to have nearly degenerate singlet and triplet states at the (U)B3LYP
      level as a free anion. Its lithium ion pair is predicted to be a ground-state
      triplet with a substantial (26 kcal/mol) singlet-triplet energy gap. Experiments
      on this anion using chemical trapping, NMR, and the Evans method strongly suggest
      that this anion is either a triplet or a ground-state singlet with a very low
      energy triplet state.

PMID- 21870823
TI  - A novel iodide-catalyzed reduction of nitroarenes and aryl ketones with H3PO2 or
      H3PO3: its application to the synthesis of a potential anticancer agent.
AB  - A novel iodide-catalyzed reduction method using hypophosphorous and/or phosphorus
      acids was developed to reduce both diaryl ketones and nitroarenes
      chemoselectively in the presence of chloro and bromo substituents in high yield.
      This efficient and practical method has been successfully applied to a large
      scale production of a potential anticancer agent.

PMID- 21870821
TI  - Structural and biochemical characterization of ZhuI aromatase/cyclase from the
      R1128 polyketide pathway.
AB  - Aromatic polyketides comprise an important class of natural products that possess
      a wide range of biological activities. The cyclization of the polyketide chain is
      a critical control point in the biosynthesis of aromatic polyketides. The
      aromatase/cyclases (ARO/CYCs) are an important component of the type II
      polyketide synthase (PKS) and help fold the polyketide for regiospecific
      cyclizations of the first ring and/or aromatization, promoting two commonly
      observed first-ring cyclization patterns for the bacterial type II PKSs: C7-C12
      and C9-C14. We had previously reported the crystal structure and enzymological
      analyses of the TcmN ARO/CYC, which promotes C9-C14 first-ring cyclization.
      However, how C7-C12 first-ring cyclization is controlled remains unresolved. In
      this work, we present the 2.4 A crystal structure of ZhuI, a C7-C12-specific
      first-ring ARO/CYC from the type II PKS pathway responsible for the production of
      the R1128 polyketides. Though ZhuI possesses a helix-grip fold shared by TcmN
      ARO/CYC, there are substantial differences in overall structure and pocket
      residue composition that may be important for directing C7-C12 (rather than C9
      C14) cyclization. Docking studies and site-directed mutagenesis coupled to an in
      vitro activity assay demonstrate that ZhuI pocket residues R66, H109, and D146
      are important for enzyme function. The ZhuI crystal structure helps visualize the
      structure and putative dehydratase function of the didomain ARO/CYCs from KR
      containing type II PKSs. The sequence-structure-function analysis described for
      ZhuI elucidates the molecular mechanisms that control C7-C12 first-ring
      polyketide cyclization and builds a foundation for future endeavors into
      directing cyclization patterns for engineered biosynthesis of aromatic
      polyketides.

PMID- 21870824
TI  - Oxo-tethered ruthenium(II) complex as a bifunctional catalyst for asymmetric
      transfer hydrogenation and H2 hydrogenation.
AB  - Newly developed oxo-tethered Ru amido complexes (R,R)-1 and their HCl adducts
      (R,R)-2 exhibited excellent catalytic performance for both asymmetric transfer
      hydrogenation and the hydrogenation of ketonic substrates under neutral
      conditions without any cocatalysts to give chiral secondary alcohols with high
      levels of enantioselectivity.

PMID- 21870825
TI  - Highly asymmetric intramolecular cyclopropanation of acceptor-substituted
      diazoacetates by Co(II)-based metalloradical catalysis: iterative approach for
      development of new-generation catalysts.
AB  - 3,5-Di(t)Bu-QingPhyrin, a new D(2)-symmetric chiral porphyrin derived from a
      chiral cyclopropanecarboxamide containing two contiguous stereocenters, has been
      developed using an iterative approach based on Co(II)-catalyzed asymmetric
      cyclopropanation of alkenes. The Co(II) complex of 3,5-Di(t)Bu-QingPhyrin,
      [Co(P2)], has proved to be a general and effective catalyst for asymmetric
      intramolecular cyclopropanation of various allylic diazoacetates (especially
      including those with alpha-acceptor substituents) in high yields with excellent
      stereoselectivities. The [Co(P2)]-based intramolecular metalloradical
      cyclopropanation provides convenient access to densely functionalized 3
      oxabicyclo[3.1.0]hexan-2-one derivatives bearing three contiguous quaternary and
      tertiary chiral centers with high enantiomeric purity.

PMID- 21870826
TI  - Engineering the unique 2D mat of graphene to achieve graphene-TiO2 nanocomposite
      for photocatalytic selective transformation: what advantage does graphene have
      over its forebear carbon nanotube?
AB  - Increasing interest has been devoted to synthesizing graphene (GR)-semiconductor
      nanocomposites as photocatalysts for potential applications, which is very
      similar to its forebear carbon nanotube (CNT)-semiconductor photocatalysts.
      Unfortunately, a thoughtful and inevitable comparison between GR- and CNT
      semiconductors as photocatalysts is often neglected in literature. This situation
      may give incomplete or exaggerated information on the contribution role of GR to
      enhance the semiconductor photocatalytic activity, as compared to CNT. Thus, our
      knowledge regarding the specific advantage of GR over CNT on how to design more
      efficient GR-semiconductor nanocomposites and understanding the origin of their
      enhanced photocatalytic performance is far from satisfactory. By taking the
      TiO(2) semiconductor as an example, we conceptually demonstrate how to synthesize
      a more efficient GR-TiO(2) nanocomposite as a visible light photocatalyst toward
      selective oxidation of alcohols under mild conditions. Comparison between GR
      TiO(2) and CNT-TiO(2) discloses the prominent advantage of GR over CNT on both
      controlling the morphology of GR-TiO(2) nanocomposite and enhancing the
      photocatalytic activity of TiO(2). This work clearly highlights the importance
      and necessity for a comparison investigation between GR- and CNT-semiconductors
      as photocatalysts, which will promote our in-depth fundamental understanding on
      the analogy and difference between GR and CNT on controlling the morphology of GR
      (or CNT)-semiconductor nanocomposites and enhancing the photocatalytic
      performance. Therefore, we appeal the photocatalysis community to pay attention
      to this respect rather than separately imposing hype on the miracle of GR in much
      the same way as its carbon forebears, which could significantly advance our
      rational fabrication of smart GR-semiconductor nanocomposites for artificial
      photosynthesis.

PMID- 21870827
TI  - Marked adsorption irreversibility of graphitic nanoribbons for CO2 and H2O.
AB  - Graphene and graphitic nanoribbons possess different types of carbon
      hybridizations exhibiting different chemical activity. In particular, the basal
      plane of the honeycomb lattice of nanoribbons consisting of sp(2)-hybridized
      carbon atoms is chemically inert. Interestingly, their bare edges could be more
      reactive as a result of the presence of extra unpaired electrons, and for
      multilayer graphene nanoribbons, the presence of terraces and ripples could
      introduce additional chemical activity. In this study, a remarkable
      irreversibility in adsorption of CO(2) and H(2)O on graphitic nanoribbons was
      observed at ambient temperature, which is distinctly different from the behavior
      of nanoporous carbon and carbon blacks. We also noted that N(2) molecules
      strongly interact with the basal planes at 77 K in comparison with edges. The
      irreversible adsorptions of both CO(2) and H(2)O are due to the large number of
      sp(3)-hybridized carbon atoms located at the edges. The observed irreversible
      adsorptivity of the edge surfaces of graphitic nanoribbons for CO(2) and H(2)O
      indicates a high potential in the fabrication of novel types of catalysts and
      highly selective gas sensors.

PMID- 21870828
TI  - Actinopolysporins A-C and tubercidin as a Pdcd4 stabilizer from the halophilic
      actinomycete Actinopolyspora erythraea YIM 90600.
AB  - Our current natural product program utilizes new actinomycetes originating from
      unexplored and underexplored ecological niches, employing cytotoxicity against a
      selected panel of cancer cell lines as the preliminary screen to identify hit
      strains for natural product dereplication, followed by mechanism-based assays of
      the purified natural products to discover potential anticancer drug leads. Three
      new linear polyketides, actinopolysporins A (1), B (2), and C (3), along with the
      known antineoplastic antibiotic tubercidin (4), were isolated from the halophilic
      actinomycete Actinopolyspora erythraea YIM 90600, and the structures of the new
      compounds were elucidated on the basis of spectroscopic data interpretation. All
      four compounds were assayed for their ability to stabilize the tumor suppressor
      programmed cell death protein 4 (Pdcd4), which is known to antagonize critical
      events in oncogenic pathways. Only 4 significantly inhibited proteasomal
      degradation of a model Pdcd4-luciferase fusion protein, with an IC50 of 0.88+/
      0.09 MUM, unveiling a novel biological activity for this well-studied natural
      product.

PMID- 21870829
TI  - Interaction of cinnamic acid derivatives with commercial hypoglycemic drugs on 2
      deoxyglucose uptake in 3T3-L1 adipocytes.
AB  - Hydroxycinnamic acid derivatives are naturally occurring substances found in
      fruits, vegetables, and flowers and are consumed as dietary phenolic compounds.
      The effect of cinnamic acid, ferulic acid, p-coumaric acid, eugenol, chlorogenic
      acid, and caffeic acid, alone and in combination with two commercial oral
      hypoglycemic drugs (OHD), namely, thiazolidinedione (THZ) and metformin, on the
      uptake of 2-deoxyglucose (2DG) by 3T3-L1 adipocytes is studied. All of the
      phytochemicals other than cinnamic acid show synergistic interaction in 2DG
      uptake with both of the OHDs. THZ (20 MUM) in combination with ferulic acid (25
      MUM) or p-coumaric acid (25 MUM) increases 2DG uptake by 7- or 6.34-fold,
      respectively, with respect to control, whereas metformin (20 MUM), along with
      ferulic acid (25 MUM) or cinnamic acid (25 MUM), increases 2DG uptake by 6.45- or
      5.87-fold, respectively, when compared to control. Chlorogenic and cinnamic acids
      increased the expression of PPARgamma, whereas other hydroxycinnamic acids
      enhanced the expression of PI3K, indicating different mechanisms of action
      between these compounds. These phytochemicals were able to reduce the expressions
      of the fatty acid synthase and HMG CoA reductase genes, indicating that they may
      be able to reduce the secondary complications caused by the accumulation of
      lipids. These studies suggest that hydroxycinnamic acid derivatives may be
      beneficial for the treatment of diabetes mellitus. They may act as a supplement
      with commercial drugs and may reduce the secondary complications caused by OHDs.

PMID- 21870830
TI  - Synthetic routes to, transformations of, and rather surprising stabilities of (N
      methyl-N-phenylcarbamoyl)sulfenyl chloride, ((N-methyl-N
      phenylcarbamoyl)dithio)carbonyl chloride, and related compounds.
AB  - The title compound classes, (carbamoyl)sulfenyl chlorides and
      ((carbamoyl)dithio)carbonyl chlorides, have been implicated previously as
      unstable, albeit trappable, intermediates in organosulfur chemistry. The present
      work reports for each of these functional groups: (i) several routes to prepare
      it in the N-methylaniline family; (ii) its direct structural characterization by
      several spectroscopic techniques; (iii) its rather unexpected stability and its
      ultimate fate when it decomposes; (iv) a series of further chemical
      transformations that give highly stable derivatives, each in turn subject to
      thorough characterization. Relevant kinetic and mechanistic experiments were
      carried out, including some with p-methyl- and 2,6-dimethyl-substituted N
      methylanilines. Given that the title compounds can be isolated and are relatively
      stable, they may find applications in the preparation of thiolyzable and/or
      photolabile protecting groups for the sulfhydryl function of cysteine and for the
      development of new protein synthesis and modification reagents.

PMID- 21870831
TI  - Anti-inflammatory triterpenoid saponins from the stem bark of Kalopanax pictus.
AB  - Five new compounds, 16,23,29-trihydroxy-3-oxo-olean-12-en-28-oic acid (1),
      4,23,29-trihydroxy-3,4-seco-olean-12-en-3-oate-28-oic acid (2), 3beta,6beta,23
      trihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (3), 3-O-[2,3-di-O
      acetyl-alpha-L-arabinopyranosyl]hederagenin 28-O-alpha-L-rhamnopyranosyl-(1->4)
      beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranoside (4), and 3-O-[3,4-di-O-acetyl
      alpha-L-arabinopyranosyl]hederagenin 28-O-alpha-L-rhamnopyranosyl-(1->4)-beta-D
      glucopyranosyl-(1->6)-beta-D-glucopyranoside (5), as well as 10 known compounds
      (6-15), were isolated from the stem bark of Kalopanax pictus. Compounds 1-5 and 7
      14 inhibited TNFalpha-induced NF-kappaB transcriptional activity in HepG2 cells
      in a dose-dependent manner, with IC50 values ranging from 0.6 to 16.4 MUM.
      Furthermore, the transcriptional inhibitory function of these compounds was
      confirmed on the basis of decreases in COX-2 and iNOS gene expression in HepG2
      cells. The structure-activity relationship of the compounds with respect to anti
      inflammatory activity is also discussed.

PMID- 21870832
TI  - Aqueous imidazole solutions: a structural perspective from simulations with high
      rank electrostatic multipole moments.
AB  - Imidazole is a small but important molecule occurring as a structure fragment in
      systems from amino acids, over ionic liquids, to synthetic polymers. Here we
      focus on the structure and dynamics of imidazole in water at ambient conditions,
      using both radial and spatial distribution functions. Molecular dynamics
      simulations were carried out for various imidazole concentrations, using a
      traditional point-charge potential and a high-rank multipolar potential. The
      difference in the description of the electrostatics leads to sizable quantitative
      differences (e.g., the diffusion coefficient) but also qualitative differences in
      the local structure. In contrast to a point-charge potential, the multipolar
      potential favors hydrogen-bonded chainlike imidazole dimers over stacked dimers.

PMID- 21870833
TI  - Protease-catalyzed oligomerization and hydrolysis of alkyl lactates involving L
      enantioselective deacylation step.

PMID- 21870834
TI  - Phonon, IR, and Raman spectra, NMR parameters, and elastic constant calculations
      for AlH3 polymorphs.
AB  - The electronic structure, lattice dynamics, and mechanical properties of AlH(3)
      phases have been studied by density functional calculations. The chemical bonding
      in different polymorphs of AlH(3) are evaluated on the basis of electronic
      structures, charge density analysis, and atomic charges, as well as bond overlap
      population analysis and the Born effective charges. The phonon dispersion
      relations and phonon density of states of all the polymorphs of AlH(3) are
      calculated by direct force-constant method. Application of pressure induces
      seqauence of phase transitions in beta-AlH(3) which are understood from the
      phonon dispersive curves of the involved phases. The previously predicted phases
      (Chem. Mater. 2008, 20, 5997) are found to be dynamically stable. The calculated
      single crystal elastic constants reveal that all the studied AlH(3) polymorphs
      are easily compressible. The chemical bonding of these polymorphs have noticeable
      covalent character (except the hp2 phase) according to the present chemical
      bonding analyses. For all these polymorphs, the NMR-related parameters, such as
      isotropic chemical shielding, quadrupolar coupling constant, and quadrupolar
      asymmetry, are also calculated. All IR- and Raman-active phonon frequencies, as
      well as the corresponding intensities, are calculated for all the AlH(3)
      polymorphs and are compared with available experimental results.

PMID- 21870835
TI  - Single- and two-photon excited fluorescence in organic nonlinear optical single
      crystal 3-(1,1-dicyanoethenyl)-1-phenyl-4,5-dihydro-1H-pyrazole.
AB  - Fluorescence of nonlinear optical organic single crystal of 3-(1,1
      dicyanoethenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (DCNP) excited by a nonabsorbed
      light pulses from Q-switched Nd:YAG laser lambda = 1064 nm as well as absorbed
      lambda = 532 nm light is reported. Two mechanisms of two-photon excited
      fluorescence are considered: (i) direct two-photon excited fluorescence and (ii)
      single-photon excitation due to reabsorption of light generated in process of
      second harmonic generation (SHG) by the crystal due to its nonlinear optical
      properties. Strong anisotropy of fluorescence that has been observed is linked
      with uniaxial molecular alignment. Fluorescence decay profile shows two-
      exponential decay with lifetimes of emitting species of 3.7 and 5.6 ns at 293 K.
      The excitation and fluorescence spectra of the DCNP single crystal have been
      measured at 294 K and in function of temperature down to 77.4 K. The strong
      bathochromic shift of fluorescence spectrum in crystal with respect to
      fluorescence of DCNP molecule in solution is observed and interpreted with
      possible formation of molecular aggregates.

PMID- 21870836
TI  - Heme-Cu bound abeta peptides: spectroscopic characterization, reactivity, and
      relevance to Alzheimer's disease.
AB  - Recently, it has been shown that heme binds to Abeta peptides which may play a
      major role in Alzheimer's disease (AD). This study illustrates that Abeta
      peptides can bind both Cu and heme cofactors at the same time. Both cofactors
      have unique spectroscopic and electrochemical features which are unaffected in
      the presence of the other, implying that they are electronically, chemically, and
      electrochemically uncoupled. These data clearly indicate that Cu cannot bind to
      three histidine residues simultaneously in Cu-Abeta complexes as previously
      proposed, since one of the histidines is involved in binding heme. The heme-Abeta
      and the heme-Cu-Abeta peptide complexes function as peroxidases. Interestingly,
      the Cu-Abeta complex also exhibits peroxidase activity, which may have
      significant implications in AD. Both Cu(+)-Abeta and heme (Fe(2+))-Abeta
      complexes reduce O(2) to H(2)O(2) quantitatively. Only one of the two electrons
      that are required for the reduction of O(2) to H(2)O(2) is derived from the
      reduced metal site, while the Tyr(10) residue of the native Abeta peptide donates
      the second electron. This Tyr(10) residue, the source of electron for the
      generation of partially reduced oxygen species (PROS, e.g., H(2)O(2)) is absent
      in rodents, which do not get affected by AD. When both heme and Cu are bound to
      the Abeta peptides, which is likely to happen physiologically, the amount of
      toxic PROS generated is maximum, implying that heme-Cu-Abeta complexes could
      potentially be most toxic for AD.

PMID- 21870837
TI  - Ultrathin ZnS single crystal nanowires: controlled synthesis and room-temperature
      ferromagnetism properties.
AB  - Highly uniform single crystal ultrathin ZnS nanowires (NWs) with 2 nm diameter
      and up to 10 MUm length were fabricated using a catalyst-free colloidal chemistry
      strategy. The nanowires crystallized in hexagonal phase structure with
      preferential growth along the direction of the (001) basal plane. The strong
      polarity of the (001) plane composed of Zn cations or S anions drives the
      oriented attachment of ZnS nanocrystals (NCs) along this direction via
      electrostatic (or dipole) interaction. The ultrathin ZnS nanowires show intrinsic
      ferromagnetism at room temperature and other unusual properties related to its
      unique nature, such as large anisotropic lattice expansion, large blue-shift of
      UV-vis absorption band of the excition, and photoluminescence spectrum of the
      exciton band edge. First-principles DFT computation results show that Zn
      vacancies can induce intrinsic ferromagnetism in these undoped ZnS NWs. The main
      source of the magnetic moment arises from the unpaired 3p electrons at S sites
      surrounding the Zn vacancies carrying the magnetic moment ranging from 0.26 to
      0.66 MU(B). Calculated results indicate that the magnetic moment of the ultrathin
      ZnS NWs can be increased by increasing the Zn vacancy concentration without
      significant energy cost. The calculated magnetization value (1.96 or 0.40 emu/g
      for Zn vacancies on the surface of NWs or inside, respectively) by Zn(53)S(54)
      supercell model is larger than our experimental value (0.12 emu/g at 1.8 K and
      0.05 emu/g at 300 K), but the ferromagnetic result is qualitatively in agreement.

PMID- 21870839
TI  - The roles of entropy and enthalpy in stabilizing ion-pairs at transition states
      in zeolite acid catalysis.
AB  - Acidic zeolites are indispensable catalysts in the petrochemical industry because
      they select reactants and their chemical pathways based on size and shape. Voids
      of molecular dimensions confine reactive intermediates and transition states that
      mediate chemical reactions, stabilizing them by van der Waals interactions. This
      behavior is reminiscent of the solvation effects prevalent within enzyme pockets
      and has analogous consequences for catalytic specificity. Voids provide the
      "right fit" for certain transition states, reflected in their lower free
      energies, thus extending the catalytic diversity of zeolites well beyond simple
      size discrimination. This catalytic diversity is even more remarkable because
      acid strength is essentially unaffected by confinement among known crystalline
      aluminosilicates. In this Account, we discuss factors that determine the "right
      fit" for a specific chemical reaction, exploring predictive criteria that extend
      the prevailing discourse based on size and shape. We link the structures of
      reactants, transition states, and confining voids to chemical reactivity and
      selectivity.  Confinement mediates enthalpy-entropy compromises that determine
      the Gibbs free energies of transition states and relevant reactants; these
      activation free energies determine turnover rates via transition state theory. At
      low temperatures (400-500 K), dimethyl ether carbonylation occurs with high
      specificity within small eight-membered ring (8-MR) voids in FER and MOR zeolite
      structures, but at undetectable rates within larger voids (MFI, BEA, FAU, and
      SiO(2)-Al(2)O(3)). More effective van der Waals stabilization within 8-MR voids
      leads to lower ion-pair enthalpies but also lower entropies; taken together,
      carbonylation activation free energies are lower within 8-MR voids. The "right
      fit" is a "tight fit" at low temperatures, a consequence of how temperature
      appears in the defining equation for Gibbs free energy.  In contrast, entropy
      effects dominate in high-temperature alkane activation (700-800 K), for which the
      "right fit" becomes a "loose fit". Alkane activation turnovers are still faster
      on 8-MR MOR protons because these transition states are confined only partially
      within shallow 8-MR pockets; they retain higher entropies than ion-pairs fully
      confined within 12-MR channels at the expense of enthalpic stability.
      Selectivities for n-alkane dehydrogenation (relative to cracking) and isoalkane
      cracking (relative to dehydrogenation) are higher on 8-MR than 12-MR sites
      because partial confinement preferentially stabilizes looser ion-pair structures;
      these structures occur later along reaction coordinates and are higher in energy,
      consistent with Marcus theory for charge-transfer reactions. Enthalpy differences
      between cracking and dehydrogenation ion-pairs for a given reactant are
      independent of zeolite structure (FAU, FER, MFI, or MOR) and predominantly
      reflect the different gas-phase proton affinities of alkane C-C and C-H bonds, as
      expected from Born-Haber thermochemical cycles. These thermochemical relations,
      together with statistical mechanics-based  treatments, predict that rotational
      entropy differences between intact reactants and ion-pair transition states cause
      intrinsic cracking rates to increase with n-alkane size.  Through these
      illustrative examples, we highlight the effects of reactant and catalyst
      structures on ion-pair transition state enthalpies and entropies. Our discussion
      underscores the role of temperature in mediating enthalpic and entropic
      contributions to free energies and, in turn, to rates and selectivities in
      zeolite acid catalysis.

PMID- 21870840
TI  - Role of exogenously supplied ferulic and p-coumaric acids in mimicking the mode
      of action of acetolactate synthase inhibiting herbicides.
AB  - Chlorsulfuron and imazethapyr (herbicides that inhibit acetolactate synthase;
      ALS, EC 4.1.3.18) produced a strong accumulation of hydroxycinnamic acids that
      was related to the induction of the first enzyme of the shikimate pathway, 3
      deoxy-d-arabino-heptulosonate 7-phosphate synthase (EC 2.5.2.54). The exogenous
      application of two hydroxycinnamic acids, ferulic and p-coumaric acids, to pea
      plants resulted in their internal accumulation, arrested growth, carbohydrate and
      quinate accumulation in the leaves, and the induction of ethanolic fermentation.
      These effects resemble some of the physiological effects detected after
      acetolactate synthase inhibition and suggest important roles for ferulic and p
      coumaric acids in the mode of action of herbicides inhibiting the biosynthesis of
      branched chain amino acids.

PMID- 21870841
TI  - Unipolar sequential circuits based on individual-carbon-nanotube transistors and
      thin-film carbon resistors.
AB  - A fabrication process for the monolithic integration of field-effect transistors
      based on individual carbon nanotubes and load resistors based on vacuum
      evaporated carbon films into fast unipolar logic circuits on glass substrates is
      reported for the first time. The individual-carbon-nanotube transistors operate
      with relatively small gate-source and drain-source voltages of 1 V and combine
      large transconductance (up to 6 MUS), large ON/OFF ratio (>10(4)), and short
      switching delay time constants (12 ns). The thin-film carbon load resistors
      provide linear current-voltage characteristics and resistances between 300 kOmega
      and 100 MOmega, depending on the layout of the resistors and the thickness of the
      vacuum-evaporated carbon films. Various combinational circuits (NAND, NOR, AND,
      OR gates) as well as a sequential circuit ( S R NAND latch) have been fabricated
      and characterized. Although these unipolar circuits cannot compete with optimized
      complementary circuits in terms of integration density and static power
      consumption, they offer the possibility of realizing air-stable, low-voltage
      integrated circuits with promising static and dynamic performance on
      unconventional substrates for large-area electronics applications, such as
      displays or sensors.

PMID- 21870842
TI  - Coexistence of magnetic and electric orderings in the metal-formate frameworks of
      [NH4][M(HCOO)3].
AB  - A family of three-dimensional chiral metal-formate frameworks of
      [NH(4)][M(HCOO)(3)] (M = Mn, Fe, Co, Ni, and Zn) displays paraelectric to
      ferroelectric phase transitions between 191 and 254 K, triggered by disorder
      order transitions of NH(4)(+) cations and their displacement within the framework
      channels, combined with spin-canted antiferromagnetic ordering within 8-30 K for
      the magnetic members, providing a new class of metal-organic frameworks showing
      the coexistence of magnetic and electric orderings.

PMID- 21870843
TI  - Analysis of Flavan-3-ols and procyanidins in food samples by reversed phase high
      performance liquid chromatography coupled to electrospray ionization tandem mass
      spectrometry (RP-HPLC-ESI-MS/MS).
AB  - Concentrations of the main dimeric and trimeric procyanidins (PC) and their
      monomeric constitutive units catechin (CT) and epicatechin (EC) were determined
      in food samples by using reversed phase high-performance liquid chromatography
      coupled to electrospray ionization tandem mass spectrometry (RP-HPLC-ESI-MS/MS).
      In a first step, 12 PCs (PC B1, B2, B3, B4, B5, B6, B7, B8, C1, C2, and A2 and
      cinnamtannin B1), of which most are not commercially available, were isolated
      from plant materials or synthesized and purified by a combination of column
      chromatographic separation techniques with different stationary phases. These PCs
      in combination with CT and EC were used as standard substances for identification
      and quantification during the following screening of food samples by RP-HPLC-ESI
      MS/MS analysis. The main focus of the newly developed RP-HPLC-ESI-MS/MS method is
      the compensation of matrix effects by using the echo-peak technique simulating
      internal standard injection. The suitability of this new method was demonstrated
      by the determination of recovery rates being 90% or higher. Use of this method
      allowed the determination of patterns and concentrations of PCs in 55 food
      samples.

PMID- 21870844
TI  - The allosteric effect of fructose bisphosphate on muscle pyruvate kinase studied
      by infrared spectroscopy.
AB  - Pyruvate kinase exhibits allosteric properties. The allosteric effect of fructose
      1,6-bisphosphate (FBP) on phosphoenolpyruvate (PEP) binding to rabbit muscle
      pyruvate kinase (PK) in the presence of various ions (Mg(2+), Mn(2+), K(+),
      Na(+)) was studied by attenuated total reflection infrared spectroscopy in
      combination with a dialysis accessory. The experiments indicated that FBP binding
      causes conformational changes of PK that are of the same order of magnitude as
      those of PEP binding. The conformational change of PEP binding to PK/Mg(2+)/K(+)
      in the presence of FBP was about twice as large as in its absence, which is
      tentatively ascribed to a higher occupancy of the closed state. The affinity for
      PEP increased in the presence of Mg(2+) and K(+). No such effects were observed
      with the other ion combinations Mn(2+)/K(+) and Mg(2+)/Na(+) or in D(2)O (with
      Mg(2+)/K(+)), and therefore we did not detect an allosteric effect on PEP binding
      under these conditions.

PMID- 21870845
TI  - Flexible carbon nanotube-based composite plates as efficient monolithic counter
      electrodes for dye solar cells.
AB  - We demonstrate a general approach to fabricate a novel low-cost, lightweight and
      flexible nanocomposite foil that can be effectively implemented as a monolithic
      counter-electrode in dye solar cells. The pivotal aim of this work was to replace
      not only the platinum catalyzer film, but even the underlying transparent
      conductive oxide-coated substrate, by means of a monolithic counter electrode
      based on carbonaceous materials. According to our approach, a proper dispersion
      of multiwalled carbon nanotubes (MWCNTs) has been added to a dilute polypropylene
      solution in toluene. The composite solution has been then adequately mixed and
      subsequently dried by means of a controlled solvent evaporation process; the
      resulting powder has been modeled by compression molding into thin plates. Four
      different series of plates have been realized by tuning the carbon nanotubes
      concentration from 5 wt % to 20 wt %. Finally, a specifically setup reactive ion
      etching treatment with oxygen plasma has been carried out onto the plate surface
      to remove the residual polymeric capping layer and allow the embedded CNTs to
      protrude on top of the surface. A fine-tuning of the morphological features has
      been made possible by adjusting the plasma etching conditions. For all the
      treated surfaces, the most meaningful electrochemical parameters have been
      quantitatively analyzed by means of both electrochemical impedance spectroscopy
      and cyclic voltammetry measurements. An as high as 13.8 mA/cm(2) photocurrent
      density, along with a solar conversion efficiency of 6.67%, has been measured for
      a dye solar cell mounting a counter-electrode based on a 20 wt % CNT
      nanocomposite.

PMID- 21870846
TI  - Calcium-induced strain in the monomer promotes dimerization in neural cadherin.
AB  - Cadherins are cell adhesion proteins that are important for tissue formation and
      integrity. Cell-cell adhesion occurs through the formation of the strand
      crossover dimer between identical cadherins on the surface of neighboring cells.
      The strand-crossover dimer forms exclusively between their EC1 domains via
      swapping of the betaA sheet by undocking the conserved tryptophan 2, W2, from its
      own hydrophobic pocket and docking it into the hydrophobic pocket of its adhesive
      partner. An interesting aspect of the system is the fact that critical
      noncovalent interactions in the monomer re-form in the dimer. Thus, as these
      noncovalent interactions are conserved, what drives the formation of dimer?
      Moreover, why is dimer formation calcium-dependent? Thus, to probe the structural
      and energetic effects of calcium on the noncovalent interactions that are
      necessary for dimer formation, we performed spectroscopic, stability, and
      assembly studies of wild-type and two mutants, W2A and E89A, of neural (N-)
      cadherin. We find that while the ionic interaction involving E89 has a minimal
      effect on the general stability of the closed conformation of the betaA sheet,
      the hydrophobic interaction involving W2 is the source of the calcium requirement
      for adhesive dimer formation. The binding of calcium creates strain in the W2
      hydrophbic pocket interaction through direct connection of E11 at the C-terminus
      of the betaA sheet to calcium. To overcome this unfavorable condition in the
      monomer, N-cadherin forms a dimer. Taken together, our data provide a
      thermodynamic basis for the calcium dependence of strand-crossover dimer
      formation in N-cadherin.

PMID- 21870847
TI  - Magnetic and magnetoelectric properties of self-assembled Fe2.5Mn0.5O4
      nanocrystals.
AB  - We report magnetoresistance of -40%, corresponding to 80% spin polarization, at
      magnetic field of 0.5 T and 200 K for oleic acid-coated Fe(2.5)Mn(0.5)O(4)
      nanocrystals (FMO NCs) self-assembled on a SiO(2)/Si substrate by drop casting
      fabrication. The FMO NCs exhibited spin glass transition around 150 K and
      nonlinear current-voltage (I-V) characteristics. Fowler-Nordheim plot of the I-V
      characteristics indicated that electrons tunnel directly barriers between the FMO
      NCs. Transmission electron microscopy revealed that the FMO NCs are elongated
      hexagon in shape with size of ~15 * 20 nm. The FMO NCs self-assembled in two
      dimension hexagonal networks of collinear ferromagnetic moments. The [111] easy
      magnetization axis of each FMO NC was parallel to each other in the hexagonal
      arrays. Geometrically frustrated lattice of collinear ferromagnetic moments
      supports both a low and a high intergranular tunneling conductance for the self
      assembled FMO NCs without and with magnetic fields, respectively.

PMID- 21870848
TI  - Water management impacts on arsenic speciation and iron-reducing bacteria in
      contrasting rice-rhizosphere compartments.
AB  - Rice cultivated on arsenic (As) contaminated-soils will accumulate variable grain
      As concentrations, as impacted by varietal differences, soil variables, and crop
      management. A field-scale experiment was conducted to study the impact of
      intermittent and continuous flooding on As speciation and microbial populations
      in rice rhizosphere compartments of soils that were either historically amended
      with As pesticide or unamended with As. Rhizosphere-soil, root-plaque, pore-water
      and grain As were quantified and speciated, and microbial populations in
      rhizosphere soil and root-plaque were characterized. Total-As concentrations in
      rhizosphere and grain were significantly lower in intermittently flooded compared
      to the continuously flooded plots (86% lower in pore-water, 55% lower in root
      plaque and 41% lower in grain samples). iAs(V), iAs(III), and DMAs(V) were the
      predominant As species detected in rhizosphere-soil and root-plaque, pore-water
      and grain samples, respectively. Relative proportions of Archaea and iron
      reducing bacteria (FeRB) were higher in rhizosphere soil compared to root-plaque.
      In rhizosphere soil, the relative abundance of FeRB was lower in intermittently
      flooded compared to continuously flooded plots, but there were no differences
      between root-plaque samples. This study has demonstrated that reductions in
      dissolved As concentrations in the rhizosphere and subsequent decreases in grain
      As concentration can be attained through water management.

PMID- 21870849
TI  - Investigation of electrochemical degradation process in polyaniline/polystyrene
      sulfonated self-assembly films by impedance spectroscopy.
AB  - In this study, the electrochemical degradation of polyaniline/polystyrene
      sulfonated (PANI/PSS) self-assembly films was investigated by an electrochemical
      impedance technique using transmission line models to fit the results. The
      experiments were performed by polarizing the working electrode at a fixed
      oxidative potential of 0.55 V. The results showed that changes in the
      electrochemical behavior of the oxidized PANI/PSS film occurred mainly in the
      polymer/solution interface by an increase in the charge transfer resistance.

PMID- 21870850
TI  - Bioavailable phosphorus in animal waste amended soils: using actual crop uptake
      and p mass balance approach.
AB  - Animal manure amended soils often contain large amounts of bioavailable
      phosphorus (P) and constitute high risk for the deterioration of surface water
      quality through eutrophication. Current standards set for the safe disposal of
      animal manure through soil application are based on the assumption that
      phosphorus in all P sources would behave similarly. The primary objective of this
      study was to understand the influence of P from several manure and mineral
      fertilizer sources applied at 0, 50, and 150 mg P kg(-1) on two measures of
      bioavailable P to six soils of different initial soil test P levels using corn
      (Zea mays L.) P uptake and an iron oxide strip method for soil analysis (FeO-P).
      Total net bioavailable P (TNBP) was calculated by subtracting total P uptake by
      corn after seven consecutive harvests in control treatments that did not receive
      P from the P uptake from P-amended treatments. Net biovavailable P after the
      first harvest (NBP1) was calculated in a similar fashion but only using data from
      the first harvest. Significant differences in TNBP and NBP1 were found when
      comparing P sources. The hog (Sus scrofa) manure had the greatest P
      bioavailability while turkey (Meleagris gallopava) litter had the lowest among
      the animal P sources across all soils and levels of P application. Significant
      differences were also found between soils with the highest amounts of TNBP and
      NBP1 found in the Woodson soil and lowest detected in the Crete soil for most P
      sources. The FeO-P method was useful in predicting TNBP from most P sources.

PMID- 21870851
TI  - Surfactant effects on efficiency enhancement of infrared-to-visible upconversion
      emissions of NaYF4:Yb-Er.
AB  - Infrared-to-visible rare earth doped upconversion phosphors that convert multiple
      photons of lower energy to higher energy photons offer a wide range of
      technological applications. The brightness (i.e., emission intensities) and
      energy efficiency of phosphors are important performance characteristics that
      determine which applications are appropriate. Optical efficiency can be used as a
      measure of the upconversion emission performance of these rare earth doped
      phosphors. In this work, hexagonal-phase NaYF(4):Yb-Er was synthesized using the
      hydrothermal method in the presence of surfactants like trioctylphosphine,
      polyethylene glycol monooleate, and polyvinylpyrrolidone. The upconversion
      emission optical efficiencies of NaYF(4):Yb-Er were measured to quantify and
      evaluate the effects of surface coatings and accurately reflect the brightness
      and energy efficiency of these phosphors. Polyvinylpyrrolidone-modified
      NaYF(4):Yb-Er particles were found to be ~5 times more efficient and brighter
      than the unmodified particles. The difference in efficiency was attributed to
      reduced reflectance losses at the particle-air interface via refractive index
      mismatch reduction between the core NaYF(4):Yb-Er particles and air using
      polyvinylpyrrolidone as a surfactant.

PMID- 21870853
TI  - Carbon and chlorine isotope ratios of chlorinated ethenes migrating through a
      thick unsaturated zone of a sandy aquifer.
AB  - Compound-specific isotope analysis (CSIA) can potentially be used to relate vapor
      phase contamination by volatile organic compounds (VOCs) to their subsurface
      sources. This field and modeling study investigated how isotope ratios evolve
      during migration of gaseous chlorinated ethenes across a 18 m thick unsaturated
      zone of a sandy coastal plain aquifer. At the site, high concentrations of
      tetrachloroethene (PCE up to 380 MUg/L), trichloroethene (TCE up to 31,600
      MUg/L), and cis-1,2-dichloroethene (cDCE up to 680 MUg/L) were detected in
      groundwater. Chlorinated ethene concentrations were highest at the water table
      and steadily decreased upward toward the land surface and downward below the
      water table. Although isotopologues have different diffusion coefficients,
      constant carbon and chlorine isotope ratios were observed throughout the
      unsaturated zone, which corresponded to the isotope ratios measured at the water
      table. In the saturated zone, TCE became increasingly depleted along a
      concentration gradient, possibly due to isotope fractionation associated with
      aqueous phase diffusion. These results indicate that carbon and chlorine isotopes
      can be used to link vapor phase contamination to their source even if extensive
      migration of the vapors occurs. However, the numerical model revealed that
      constant isotope ratios are only expected for systems close to steady state.

PMID- 21870852
TI  - Critical insights into cardiovascular disease from basic research on the
      oxidation of phospholipids: the gamma-hydroxyalkenal phospholipid hypothesis.
AB  - Basic research, exploring the hypothesis that gamma-hydroxyalkenal phospholipids
      are generated in vivo through oxidative cleavage of polyunsaturated
      phospholipids, is delivering a bonanza of molecular mechanistic insights into
      cardiovascular disease. Rather than targeting a specific pathology, these studies
      were predicated on the presumption that a fundamental understanding of lipid
      oxidation is likely to provide critical insights into disease processes. This
      investigational approach, from the chemistry of biomolecules to disease
      phenotype, that complements the more common opposite paradigm, is proving
      remarkably productive.

PMID- 21870854
TI  - Comprehensive tissue processing strategy for quantitative proteomics of formalin
      fixed multiple sclerosis lesions.
AB  - Formalin-fixed (FF) autopsy tissue comprises the bulk of existing Multiple
      Sclerosis (MSc) pathology archives, providing a rich pool of material for
      biomarker discovery and disease characterization. Here, we present the
      development of a heat-induced extraction protocol for the proteomic analysis of
      FF brain tissue, its application to the study of lesion remyelination and its
      failure in MSc. A 4-round extraction strategy was optimized using FF tissue
      leading to a 35% increase in the number of proteins identified compared to a
      single extraction; and a 65% increase in proteins identified with >=4 peptides.
      Histological staining of sections with oil red O and luxol fast blue-periodic
      acid Schiff, required to characterize MSc lesions was found to have minimal
      effect on LC-MS/MS. The application of the optimized protocol to chronic
      demyelinated and remyelinated FF MSc lesions and the adjacent periplaque white
      matter, isolated through laser guided manual dissection from 3 patients,
      identified 428 unique proteins (0.2% FDR) using LC-MS/MS. Comparison of the
      lesion types using iTRAQ and 2-D LC-MS/MS revealed 82 differentially expressed
      proteins. Protein quantitation by iTRAQ and spectral counting was well-correlated
      (r(s)= 0.7653; p < 10(-30)). The data generated from this work illustrates the
      scope of the methodology and provides insights into the pathogenesis of MSc and
      remyelination.

PMID- 21870855
TI  - Cyclic biamperometry at micro-interdigitated electrodes.
AB  - Cyclic biamperometry was studied as an analytical method for use with
      commercially available, comb-type, coplanar microinterdigitated electrodes
      (MUIDEs), using the ferri-/ferrocyanide redox couple as a model analyte. The
      MUIDEs studied in this work were made of gold that had been deposited onto a Ti/W
      adhesion layer on borosilicate glass chips and had 5 and 10 MUm bands with equal
      gap sizes. Close proximity of the two working electrodes, and their
      interdigitation, resulted in signal amplification by redox cycling. Results were
      compared with those obtained by cyclic voltammetry, where one of the two IDE
      electrodes was used as the working electrode and external reference and auxiliary
      electrodes were used. Amplification factors of almost 20 were achieved due to
      redox cycling. Attempts to apply cyclic voltammetry to the MUIDEs, with one of
      the combs as the working and the other as the auxiliary electrode, were
      unsuccessful due to corrosion of the auxiliary electrode comb. Results of this
      study, and the electrochemically unique feature of biamperometry to probe but not
      change the net contents of the medium under examination, suggest the
      applicability of scanning biamperometry at MUIDEs to the very small volumes and
      electrochemical cell dimensions that are now of great interest.

PMID- 21870856
TI  - Preparation and identification of monoclonal antibody against abrin-a.
AB  - BALB/c mice were immunized four times with formalin-prepared abrin-a. Using the
      polyethylene glycol method, immunized splenocytes were isolated and fused with
      SP2/0 cells. An indirect ELISA was established and used to detect positive clones
      secreting monoclonal antibodies (mAbs) against abrin-a. After analysis, three
      hybridoma clones secreting IgG-subtype mAbs were obtained. The antibodies were
      purified from the hybridoma growth medium using protein A or G affinity
      chromatography. Western blot analysis was used to analyze the antigenic epitopes
      on abrin-a recognized by the mAbs. The mAbs were specific for abrin-a, with no
      detectable cross-reactivity with several homologous toxins and associated
      agglutinins. Sandwich ELISA was then developed using these mAbs, which had a
      detection limit for abrin-a of 7.8 ng/mL.

PMID- 21870857
TI  - Quasi-free-standing epitaxial graphene on SiC (0001) by fluorine intercalation
      from a molecular source.
AB  - We demonstrated a novel method to obtain charge neutral quasi-free-standing
      graphene on SiC (0001) from the buffer layer using fluorine from a molecular
      source, fluorinated fullerene (C(60)F(48)). The intercalated product is stable
      under ambient conditions and resistant to elevated temperatures of up to 1200 
      degrees C. Scanning tunneling microscopy and spectroscopy measurements are
      performed for the first time on such quasi-free-standing graphene to elucidate
      changes in the electronic and structural properties of both the graphene and
      interfacial layer. Novel structures due to a highly localized perturbation caused
      by the presence of adsorbed fluorine were produced in the intercalation process
      and investigated. Photoemission spectroscopy is used to confirm these electronic
      and structural changes.

PMID- 21870859
TI  - Light-controlled bioelectrochemical sensor based on CdSe/ZnS quantum dots.
AB  - This study reports on the oxygen sensitivity of quantum dot electrodes modified
      with CdSe/ZnS nanocrystals. The photocurrent behavior is analyzed for dependence
      on pH and applied potential by potentiostatic and potentiodynamic measurements.
      On the basis of the influence of the oxygen content in solution on the
      photocurrent generation, the enzymatic activity of glucose oxidase is evaluated
      in solution. In order to construct a photobioelectrochemical sensor which can be
      read out by illuminating the respective electrode area, two different
      immobilization methods for the fixation of the biocatalyst have been
      investigated. Both covalent cross-linking and layer-by-layer deposition of GOD by
      means of the polyelectrolyte polyallylamine hydrochloride show that a sensor
      construction is possible. The sensing properties of this type of electrode are
      drastically influenced by the amount and density of the enzyme on top of the
      quantum dot layer, which can be advantageously adjusted by the layer-by-layer
      technique. By depositing four bilayers [GOD/PAH](4) on the CdSe/ZnS electrode, a
      fast-responding sensor for the concentration range of 0.1-5 mM glucose can be
      prepared. This study opens the door to multianalyte detection with a
      nonstructured sensing electrode, localized enzymes, and spatial read-out by
      light.

PMID- 21870858
TI  - Methionine ligand lability in bacterial monoheme cytochromes c: an
      electrochemical study.
AB  - The direct electrochemical analysis of adsorbed redox active proteins has proven
      to be a powerful technique in biophysical chemistry, frequently making use of the
      electrode material pyrolytic "edge-plane" graphite. However, many heme-bearing
      proteins such as cytochromes c have been also examined systematically at
      alkanethiol-modified gold surfaces, and previously we reported the
      characterization of the redox properties of a series of bacterial cytochromes c
      in a side-by-side comparison of carbon and gold electrode materials. In our prior
      findings, we reported an unanticipated, low potential (E(m) ~ -100 mV vs SHE)
      redox couple that could be analogously observed when a variety of monoheme
      cytochromes c are adsorbed onto carbon-based electrodes. Here we demonstrate that
      our prior phenomological data can be understood quantitatively in the loss of the
      methionine ligand of the heme iron, using the cytochrome c from  Hydrogenbacter
      thermophilum  as a model system. Through the comparison of wild-type protein with
      M61H and M61A mutants, in direct electrochemical analyses conducted as a function
      of temperature and exogenous ligand concentration, we are able to show that Met
      ligated cytochromes c have a propensity to lose their Met ligand at graphite
      surfaces, and that energetics of this process (6.3 +/- 0.2 kJ/mol) is similar to
      the energies associated with "foldons" of known protein folding pathways.

PMID- 21870861
TI  - A mechanistic hypothesis for the cytochrome P450-catalyzed cis-trans
      isomerization of 4-hydroxytamoxifen: an unusual redox reaction.
AB  - We provide a detailed description of the cis-trans isomerization of 4
      hydroxytamoxifen/endoxifen catalyzed by several isoforms from the cytochrome P450
      (CYP) superfamily, including CYP1B1, CYP2B6, and CYP2C19. We show that the
      reactions mainly involve redox processes catalyzed by CYP. DFT calculation
      results strongly suggest that the isomerization occurs via a cationic
      intermediate. The cationic cis-isomer is more than 3 kcal/mol more stable than
      the trans form, resulting in an easier conversion from trans-to-cis than cis-to
      trans. The cis-trans isomerization is a rarely reported CYP reaction and is
      ascribed to the lack of a second abstractable proton on the ethenyl group of the
      triarylvinyl class of substrates. The cationic intermediates thus formed instead
      of the stable dehydrogenation products allow for isomerization to occur. As a
      comparison, the reactions for the tamoxifen derivatives are compared to those of
      other substrates, 4-hydroxyacetanilide and raloxifene, for which the stable
      dehydrogenation products are formed.

PMID- 21870860
TI  - Influence of substrate modification and C-terminal truncation on the active site
      structure of substrate-bound heme oxygenase from Neisseriae meningitidis. A 1H
      NMR study.
AB  - Heme oxygenase (HO), from the pathogenic bacterium N. meningitidis(NmHO), which
      secures host iron, shares many properties with mammalian HOs but also exhibits
      some key differences. The crystal structure appears more compact, and the crystal
      undetected C-terminus interacts with substrate in solution. The unique nature of
      substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in
      NmHO are probed by 2D (1)H NMR to reveal unique structural features controlling
      substrate orientation. The thermodynamics of substrate orientational isomerism
      are mapped for substrates with individual vinyl -> methyl -> hydrogen
      substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly
      stronger orientational preference, reflecting much stronger and selective pyrrole
      I/II interactions with the protein matrix, than in mammalian HOs. Thus, replacing
      bulky vinyls with hydrogens results in a 180 degrees  rotation of substrate about
      the alpha,gamma-meso axis in the active site. A "collapse" of the substrate
      pocket as substrate size decreases is reflected in movement of helix-2 toward the
      substrate as indicated by significant and selective increased NOESY cross-peak
      intensity, increase in steric Fe-CN tilt reflected in the orientation of the
      major magnetic axis, and decrease in steric constraints controlling the rate of
      aromatic ring reorientation. The active site of NmHO appears "stressed" for
      native protohemin, and its "collapse" upon replacing vinyls by hydrogen leads to
      a factor ~10(2) increase in substrate affinity. Interaction of the C-terminus
      with the active site destabilizes the crystallographic protohemin orientation by
      ~0.7 kcal/mol, which is consistent with optimizing the His207-Asp27 H-bond.
      Implications of the active site "stress" for product release are discussed.

PMID- 21870862
TI  - Rapid shape-based ligand alignment and virtual screening method based on
      atom/feature-pair similarities and volume overlap scoring.
AB  - Shape-based methods for aligning and scoring ligands have proven to be valuable
      in the field of computer-aided drug design. Here, we describe a new shape-based
      flexible ligand superposition and virtual screening method, Phase Shape, which is
      shown to rapidly produce accurate 3D ligand alignments and efficiently enrich
      actives in virtual screening. We describe the methodology, which is based on the
      principle of atom distribution triplets to rapidly define trial alignments,
      followed by refinement of top alignments to maximize the volume overlap. The
      method can be run in a shape-only mode or it can include atom types or
      pharmacophore feature encoding, the latter consistently producing the best
      results for database screening. We apply Phase Shape to flexibly align molecules
      that bind to the same target and show that the method consistently produces
      correct alignments when compared with crystal structures. We then illustrate the
      effectiveness of the method for identifying active compounds in virtual screening
      of eleven diverse targets. Multiple parameters are explored, including atom
      typing, query structure conformation, and the database conformer generation
      protocol. We show that Phase Shape performs well in database screening
      calculations when compared with other shape-based methods using a common set of
      actives and decoys from the literature.

PMID- 21870863
TI  - Critical residue that promotes protein dimerization: a story of partially exposed
      Phe25 in 14-3-3sigma.
AB  - Many proteins exist and function as oligomers. While hydrophobic interactions
      have been recognized as the major driving force for oligomerization, detailed
      molecular mechanisms for the assembly are unknown. Here, we used 14-3-3sigma as a
      model protein and investigated the role of hydrophobic residues at the dimeric
      interface using MD simulations and coimmunoprecipitations. We found that a half
      exposed and half-buried residue in the interface, Phe(25), plays a more important
      role in promoting homodimerization than the hydrophobic core residues by
      organizing both favorable hydrophobic and hydrophilic interactions. Phe(25) is
      critical in packing and stabilizing hydrophobic core residues. We conclude that
      the structural stability of hydrophobic cores is critical for a stable homodimer
      complex and this stable property can be bestowed by residues outside of
      hydrophobic core. The important organizing activity of Phe(25) for
      homodimerization of 14-3-3sigma originates from its unique physical location,
      rigidity, size, and hydrophobicity. Thus, hydrophobic residues that are not
      deeply buried at the oligomeric interface may play important but different roles
      from the buried core residues and they may promote oligomerization by organizing
      co-operativity of core and other residues for favorable hydrophobic and
      electrostatic interactions.

PMID- 21870864
TI  - Solvent interaction energy calculations on molecular dynamics trajectories:
      increasing the efficiency using systematic frame selection.
AB  - End-point methods such as linear interaction energy (LIE) analysis, molecular
      mechanics generalized Born solvent-accessible surface (MM/GBSA), and solvent
      interaction energy (SIE) analysis have become popular techniques to calculate the
      free energy associated with protein-ligand binding. Such methods typically use
      molecular dynamics (MD) simulations to generate an ensemble of protein structures
      that encompasses the bound and unbound states. The energy evaluation method (LIE,
      MM/GBSA, or SIE) is subsequently used to calculate the energy of each member of
      the ensemble, thus providing an estimate of the average free energy difference
      between the bound and unbound states. The workflow requiring both MD simulation
      and energy calculation for each frame and each trajectory proves to be
      computationally expensive. In an attempt to reduce the high computational cost
      associated with end-point methods, we study several methods by which frames may
      be intelligently selected from the MD simulation including clustering and address
      the question of how the number of selected frames influences the accuracy of the
      SIE calculations.

PMID- 21870865
TI  - Normal mode analysis of Trp RNA binding attenuation protein: structure and
      collective motions.
AB  - The Trp RNA-binding protein (TRAP) has a toroidal topology and a perfect 11-fold
      symmetry, which makes it an excellent candidate for a vibrational study of
      elastic properties. Normal mode analysis in combination with correlation matrix
      calculations was used to detect collective low-frequency motions in TRAP. The
      results reveal the presence of highly correlated modes at the lower end of the
      spectrum, which directly reflect the annular and toroidal topology. The integral
      of the correlations over the low-frequency torsional part of the vibrational
      spectrum further demonstrates the relative rigidity of the 11 monomer building
      blocks of TRAP. The internal flexibility of each monomer and the effects of Trp
      binding were also examined. The study clearly shows the determining influence of
      symmetry and topology on the elastic properties and also offers a detailed view
      on the Trp affinity of TRAP.

PMID- 21870866
TI  - Correlation analyses on binding affinity of sialic acid analogues and anti
      influenza drugs with human neuraminidase using ab initio MO calculations on their
      complex structures--LERE-QSAR analysis (IV).
AB  - We carried out full ab initio fragment molecular orbital (FMO) calculations for
      complexes comprising human neuraminidase-2 (hNEU2) and sialic acid analogues
      including anti-influenza drugs zanamivir (Relenza) and oseltamivir (Tamiflu) in
      order to examine the variation in the observed inhibitory activity toward hNEU2
      at the atomic and electronic levels. We recently proposed the LERE (linear
      expression by representative energy terms)-QSAR (quantitative structure-activity
      relationship) procedure. LERE-QSAR analysis quantitatively revealed that the
      complex formation is driven by hydrogen-bonding and electrostatic interaction of
      hNEU2 with sialic acid analogues. The most potent inhibitory activity, that of
      zanamivir, is attributable to the strong electrostatic interaction of a
      positively charged guanidino group in zanamivir with negatively charged amino
      acid residues in hNEU2. After we confirmed that the variation in the observed
      inhibitory activity among sialic acid analogues is excellently reproducible with
      the LERE-QSAR equation, we examined the reason for the remarkable difference
      between the inhibitory potencies of oseltamivir as to hNEU2 and influenza A virus
      neuraminidase-1 (N1-NA). Several amino acid residues in close contact with a
      positively charged amino group in oseltamivir are different between hNEU2 and N1
      NA. FMO-IFIE (interfragment interaction energy) analysis showed that the
      difference in amino acid residues causes a remarkably large difference between
      the overall interaction energies of oseltamivir with hNEU2 and N1-NA. The current
      results will be useful for the development of new anti-influenza drugs with high
      selectivity and without the risk of adverse side effects.

PMID- 21870867
TI  - Inhibition of the replication of hepatitis B virus in vitro by pu-erh tea
      extracts.
AB  - Hepatitis B virus (HBV) is one of the most widespread viral infections in the
      world and poses a significant global public health problem. The implementation of
      effective vaccination programs has resulted in a significant decrease in the
      incidence of acute hepatitis B. Nevertheless, there is still a need for as many
      effective anti-HBV drugs as possible. In this study, the role of pu-erh tea
      extracts (PTE) against HBV was analyzed in vitro by using a stably HBV
      transfected cell line HepG2 2.2.15. The MTT assay showed that PTE and its active
      components (tea polyphenols, theaflavins, and theanine) presented low
      cytotoxicity. ELISA analysis revealed that PTE effectively reduced the secretion
      of HBeAg, but any one of the active components alone showed weaker efficacy,
      suggesting that the anti-HBV activity of PTE might be a synergetic effect of
      different components. RT-PCR and luciferase assay showed that PTE suppressed HBV
      mRNA expression while leaving four HBV promoter transcriptional activities
      unchanged. Fluorescence quantitative PCR results demonstrated that PTE
      dramatically diminished HBV DNA produced in cell supernatants as well as
      encapsidated DNA in intracellular core particles. Finally, PTE significantly
      reduced intracellular reactive oxygen species (ROS) level. This study is the
      first to demonstrate that PTE possesses anti-HBV ability and could be used as a
      potential treatment against HBV infection with an additional merit of low
      cytotoxicity.

PMID- 21870868
TI  - Surface molecular imprinted layer-by-layer film attached to a porous membrane for
      selective filtration.
AB  - A surface molecular imprinted layer-by-layer (SMILbL) film was fabricated on a
      polyethersulfone (PES) porous membrane substrate for selective filtration of
      cations and anions. The LbL deposition procedure and the ultraviolet (UV) cross
      linking of the modified membrane were monitored by attenuated total reflection
      infrared (ATR-IR) spectra. The SMILbL-PES membrane with 4.5 bilayers of
      diazoresin (DAR)/poly(acrylic acid) complexed with 5,10,15,20-tetrakis(4
      (trimethylammonio)-phenyl)-21H,23H-porphyrin tetratosylate (PAA-Por(4+))
      effectively reduced the permeation velocity of Por(4+) after washing the Por(4+)
      template out. In comparison to a control film DAR/PAA-modified PES membrane
      (ConLbL-PES) in a dialysis experiment, the SMILbL-PES membrane exhibited better
      selectivity for permeation of 5,10,15,20-tetraphenyl-21H,23H-porphine
      p,p',p",p'''-tetrasulfonic acid tetrasodium hydrate (Por(4-)) against permeation
      of Por(4+). In pressure-driven transport experiments, the SMILbL-PES membrane
      showed a much longer blocking time for Por(4+) than for Por(4-), indicating the
      selective loading of Por(4+) into the SMILbL film. The surface charge of the
      SMILbL-PES membrane after Por(4+) loading was higher than that of other
      membranes, resulting in an enhanced rejection ability of the SMILbL-PES membrane
      to Por(4+) caused by Coulomb repulsion. A possible mechanism was proposed as
      follows. The binding sites generated through imprinting in the SMILbL-PES
      membrane enable loading of a larger amount of Por(4+). The stronger repulsion
      between Por(4+) and the SMILbL film may cause the main contribution to the
      selective rejection of Por(4+). It can be easily imagined that this concept can
      be extended to the construction of composite membranes from other imprinting
      systems.

PMID- 21870869
TI  - Polymeric sequence probe for single DNA detection.
AB  - A polynucleotide probe, polymeric sequence probe (PSP), was developed for single
      molecular detections. PSP is a single-stranded DNA molecule with ~2000 tandem
      repeat target-binding sequences and label-binding sequences. A single PSP can
      bind to multiple fluorescent complementary oligos to generate a strong
      fluorescence signal. Single target molecules bound to PSPs can be clearly
      visualized by a conventional fluorescence microscope. An ultrasensitive PSP-based
      assay for Mycobacterium tuberculosis was demonstrated.

PMID- 21870870
TI  - Preparation of imprinted polymers at surface of magnetic nanoparticles for the
      selective extraction of tadalafil from medicines.
AB  - In this paper, highly selective core-shell molecularly imprinted polymers (MIPs)
      of tadalafil on the surface of magnetic nanoparticles (MNPs) were prepared. Three
      widely used functional monomers 2-(trifluoromethyl) acrylic acid (TFMAA), acrylic
      acid (AA), and methacrylic acid (MAA) were compared theoretically as the
      candidates for MIP preparation. MIP-coated magnetic nanoparticles (MIP-coated
      MNPs) showed large adsorption capacity, high recognition ability, and fast
      binding kinetics for tadalafil. Furthermore, because of the good magnetic
      properties, MIP-coated MNPs can achieve rapid and efficient separation with an
      external magnetic field simply. The resulting MIP-coated MNPs were used as
      dispersive solid-phase extraction (DSPE) materials coupled with HPLC-UV for the
      selective extraction and detection of tadalafil from medicines (herbal sexual
      health products). Encouraging results were obtained. The amounts of tadalafil
      that were detected from the herbal sexual health product was 43.46 nmol g(-1),
      and the recoveries were in the range of 87.36-90.93% with the RSD < 6.55%.

PMID- 21870871
TI  - Synthesis of monodisperse fluorinated silica nanoparticles and their
      superhydrophobic thin films.
AB  - Monodispersive silica nanoparticles have been synthesized via the Stober process
      and further functionalized by adding fluorinated groups using fluoroalkylsilane
      in an ethanolic solution. In this process, six different sizes of fluorinated
      silica nanoparticles of varying diameter from 40 to 300 nm are prepared and used
      to deposit thin films on aluminum alloy surfaces using spin coating processes.
      The functionalization of silica nanoparticles by fluorinated group has been
      confirmed by the presence C-F bonds along with Si-O-Si bonds in the thin films as
      analyzed by Fourier transform infrared spectroscopy (FTIR). The surface
      roughnesses as well as the water contact angles of the fluorinated silica
      nanoparticle containing thin films are found to be increased with the increase of
      the diameter of the synthesized fluorinated silica nanoparticles. The thin films
      prepared using the fluorinated silica nanoparticles having a critical size of 119
      +/- 12 nm provide a surface roughness of ~0.697 MUm rendering the surfaces
      superhydrophobic with a water contact angle of 151 +/- 4 degrees . The roughness
      as well as the water contact angle increases on the superhydrophobic thin films
      with further increase in the size of the fluorinated silica nanoparticles in the
      films.

PMID- 21870872
TI  - Are hydrotropes distinct from surfactants?
AB  - The physicochemical properties of a homologous series of sodium p-n
      alkylbenzoates have been investigated. The objective was to determine whether
      there is a clear transition point from hydrotropic to surfactant-like behavior
      with increasing alkyl chain length n, so as to shed clear light on the
      aggregation mechanism of so-called "hydrotropes". Electrical conductivity
      measurements were used for a first estimation of the critical aggregation
      concentrations (cac). As for classical surfactants, log(cac) depends on alkyl
      chain length n, but two branches of behavior were observed: one having a gradient
      typical of long chain fatty acid salts and the other with a more shallow
      dependence. Surface tension (gamma) measurements of high purity aqueous solutions
      were used to generate limiting headgroup areas A(cac), which were in the range
      (40-50 A(2)) being consistent with monolayer formation. Small-angle neutron
      scattering conclusively shows that the lower chain length homologues (classed as
      hydrotropes) exhibit sharp transitions in aggregation as a function of bulk
      concentration, typical of regular surfactants. As such, there is little to
      suggest from this study that hydrotropes differ in association behavior from
      regular surfactants.

PMID- 21870873
TI  - Development of the novel PEG-PE-based polymer for the reversible attachment of
      specific ligands to liposomes: synthesis and in vitro characterization.
AB  - Surface grafting of liposomes with the wide variety of ligands including
      antibodies and other proteins is a promising approach for targeted delivery of
      therapeutics. In this paper, we describe a simple method of synthesizing a
      hydrazine-functionalized poly(ethylene glycol)-phosphatidylethanolamine (PEG-PE)
      based amphiphilic polymer which can conjugate a variety of ligands via a
      reversible, pH-cleavable bond. In this method, the targeting ligand is attached
      to the distal end of the PEG chain, which facilitates its easy access to the
      targeted site of interaction. The reversible attachment of targeting ligands is
      useful especially in multifunctional liposomal systems, whereafter successfully
      performing the function of targeting to the specific site, the bulky ligands,
      such as proteins or antibodies, are cleaved off in response to an environmental
      stimulus to expose some other functionalities such as ligands for intracellular
      penetration or organelle-specific targeting. To investigate the applicability of
      the protocol, the model ligands monoclonal antinucleosome antibody 2C5 and
      antimyosin antibody 2G4, and glycoproteins concanavalin A (Con-A) and avidin were
      conjugated to the synthesized polymer and incorporated into liposomes. In vitro
      assays including biochemical, enzyme-linked immunosorbent, fluorescence
      microscopy, and flow cytometry were used to confirm three key characteristics of
      the modified and/or liposome-attached proteins: successful conjugation of the
      targeting ligands to the polymer, preservation of specific activity of the
      ligands after the conjugation and liposome attachment, and the facile pH
      sensitive ligand detachment. Monoclonal antibody 2C5 and 2G4, immobilized on the
      liposome surface, retained their binding affinity to corresponding antigens as
      confirmed by ELISA. The Con A-bearing liposomes showed significantly higher
      agglutination in the presence of its substrate mannan compared to plain liposomes
      (PL) and avidin-functionalized liposomes bound specifically with biotin-agarose.
      The study on the pH-dependence showed that almost 80% of the hydrazone bond was
      cleaved after rather brief preincubation of the immunoliposomes at pH 5 for 0.5
      to 1 h. Fluorescence microscopy and flow cytometry analysis of cancer cells (HeLa
      and MCF-7) treated with cancer cell-specific targeting ligand mAb 2C5-bearing
      liposomes showed enhanced cellular binding. Studies at low pH clearly confirmed
      the easy cleavability of the targeting ligand from the liposomes resulting in
      significantly less or virtually no cellular association.

PMID- 21870875
TI  - Heterogeneous reaction of suspended phosmet particles with NO3 radicals.
AB  - As an organophosphorous insecticide, phosmet is widely used for plant protection
      as well as against the ectoparasites on productive livestock. It emits into the
      atmosphere in both gas and particulate phases via spray drift from treatments and
      postapplication emissions, but its degradation in the atmosphere is not well
      known up to now. In this study, the heterogeneous reaction of phosmet absorbed on
      the azelaic acid particles with NO(3) radicals is investigated in real-time using
      a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer
      (VUV-ATOFMS). Two primary products and their nitro-substituted derivates are
      observed. The apparent reaction rate of phosmet particles with NO(3) radicals is
      also obtained by a relative rate method with isoprene and 1,4-cyclohexadiene as
      the reference compounds. The concentrations of the reference substance and
      phosmet particles are synchronously detected with an atmospheric gas analysis
      mass spectrometer and the VUV-ATOFMS. Under the experimental conditions, the
      average apparent reaction rate obtained is (1.92 +/- 0.09) * 10(-12) cm(3)
      molecule(-1) s(-1), and the corresponding atmospheric lifetime toward NO(3)
      radicals is roughly estimated to be ~0.3 h.

PMID- 21870876
TI  - Synthesis of W18O49 nanorod via ammonium tungsten oxide and its interesting
      optical properties.
AB  - W(18)O(49) nanorods were synthesized by pyrolyzing (NH(4))(x)WO(3+x/2) nanorods
      precursors, which were prepared by a hydrothermal reaction using sulfate as a
      structure-directing agent, in a reductive atmosphere of H(2)(5 vol %)/N(2) at 500
      degrees C for 1 h. W(18)O(49) nanorods showed high transmittance in the visible
      region as well as excellent shielding properties of NIR lights. A simulated
      experiment revealed that excellent heat insulating performance can be realized by
      applying a 70% visible light transparent W(18)O(49) coating on a quartz glass.
      Meanwhile, the W(18)O(49) nanorods also showed strong absorption of NIR light and
      instantaneous conversion of photoenergy to heat. In a word, W(18)O(49) nanorods
      hold interesting optical properties and are a promising material in a wide range
      of applications.

PMID- 21870874
TI  - Synthesis, biological evaluation, and automated docking of constrained analogues
      of the opioid peptide H-Dmt-D-Ala-Phe-Gly-NH2 using the 4- or 5-methyl
      substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one scaffold.
AB  - The Phe(3) residue of the N-terminal tetrapeptide of dermorphin (H-Dmt-d-Ala-Phe
      Gly-NH(2)) was conformationally constrained using 4- or 5-methyl-substituted 4
      amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) stereoisomeric scaffolds.
      Several of the synthesized peptides were determined to be high affinity agonists
      for the MU opioid receptor (OPRM) with selectivity over the delta opioid receptor
      (OPRD). Interesting effects of the Aba configuration on ligand binding affinity
      were observed. H-Dmt-d-Ala-erythro-(4S,5S)-5-Me-Aba-Gly-NH(2)9 and H-Dmt-threo
      (4R,5S)-5-Me-Aba-Gly-NH(2)12 exhibited subnanomolar affinity for OPRM, while they
      possess an opposite absolute configuration at position 4 of the Aba ring.
      However, in the 4-methyl substituted analogues, H-Dmt-d-Ala-(4R)-Me-Aba-Gly
      NH(2)14 was significantly more potent than the (4S)-derivative 13. These
      unexpected results were rationalized using the binding poses predicted by
      molecular docking simulations. Interestingly, H-Dmt-d-Ala-(4R)-Me-Aba-Gly-NH(2)14
      is proposed to bind in a different mode compared with the other analogues.
      Moreover, in contrast to Ac-4-Me-Aba-NH-Me, which adopts a beta-turn in solution
      and in the crystal structure, the binding mode of this analogue suggests an
      alternative receptor-bound conformation.

PMID- 21870878
TI  - Inhalation by design: novel tertiary amine muscarinic M3 receptor antagonists
      with slow off-rate binding kinetics for inhaled once-daily treatment of chronic
      obstructive pulmonary disease.
AB  - A novel tertiary amine series of potent muscarinic M(3) receptor antagonists are
      described that exhibit potential as inhaled long-acting bronchodilators for the
      treatment of chronic obstructive pulmonary disease. Geminal dimethyl
      functionality present in this series of compounds confers very long dissociative
      half-life (slow off-rate) from the M(3) receptor that mediates very long-lasting
      smooth muscle relaxation in guinea pig tracheal strips. Optimization of
      pharmacokinetic properties was achieved by combining rapid oxidative clearance
      with targeted introduction of a phenolic moiety to secure rapid glucuronidation.
      Together, these attributes minimize systemic exposure following inhalation,
      mitigate potential drug-drug interactions, and reduce systemically mediated
      adverse events. Compound 47 (PF-3635659) is identified as a Phase II clinical
      candidate from this series with in vivo duration of action studies confirming its
      potential for once-daily use in humans.

PMID- 21870879
TI  - Influence of turn (or fold) and local charge in fragmentation of the peptide
      analogue molecule CH3CO-Gly-NH2 following single-photon VUV (118.22 nm)
      ionization.
AB  - The radical cationic reactivity of the peptide analogue molecule CH(3)CO-Gly
      NH(2) is addressed both experimentally and theoretically. The radical cation
      intermediate of CH(3)CO-Gly-NH(2) is created by single-photon ionization of this
      molecule at 118.22 nm (~10.5 eV). The two most stable conformers (C(7) and C(5))
      of this molecule exhibit different folds along the backbone: the C(7) conformer
      has a gamma-turn structure, and the C(5) conformer has a beta-strand structure.
      The experimental results show that the radical cation intermediate of CH(3)CO-Gly
      NH(2) dissociates and generates a fragment-ion signal at 73 amu that is observed
      through TOFMS. Theoretical results show how the fragment-ion signal at 73 amu is
      generated by only one conformer of CH(3)CO-Gly-NH(2) (C(7)) and how local charge
      and specific hydrogen bonding in the molecule influence fragmentation of the
      radical cation intermediate of CH(3)CO-Gly-NH(2). The specific fold of the
      molecule controls fragmentation of this reactive radical cation intermediate.
      Whereas the radical cation of the C(7) conformer dissociates through a hydrogen
      transfer mechanism followed by HNCO elimination, the radical cation of the C(5)
      conformer does not dissociate at all. CASSCF calculations show that positive
      charge in the radical cationic C(7) conformer is localized at the NH(2)CO moiety
      of the molecular ion. This site-specific localization of the positive charge
      enhances the acidity of the terminal NH(2) group, facilitating hydrogen transfer
      from the NH(2) to the COCH(3) end of the molecular ion. Positive charge in the
      C(5) conformer of the CH(3)CO-Gly-NH(2) radical cation is, however, localized at
      the COCH(3) end of the molecular ion, and this conformer does not have enough
      energy to surmount the energy barrier to dissociation on the ion potential energy
      surface. CASSCF results show that conformation-specific localization of charge in
      the CH(3)CO-Gly-NH(2) molecular ion occurs as a result of the different hydrogen
      bonding interactions involved in the different molecular conformers.

PMID- 21870877
TI  - Synthesis and characterization of high-affinity 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene-labeled fluorescent ligands for human beta-adrenoceptors.
AB  - The growing practice of exploiting noninvasive fluorescence-based techniques to
      study G protein-coupled receptor pharmacology at the single cell and single
      molecule level demands the availability of high-quality fluorescent ligands. To
      this end, this study evaluated a new series of red-emitting ligands for the human
      beta-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol,
      alprenolol, and pindolol, the synthesized linker-modified congeners were coupled
      to the commercially available fluorophore BODIPY 630/650-X. This yielded high
      affinity beta-adrenoceptor fluorescent ligands for both the propranolol and
      alprenolol derivatives; however, the pindolol-based products displayed lower
      affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had
      the highest affinity (log K(D) of -9.53 and -8.46 as an antagonist of functional
      beta2- and beta1-mediated responses, respectively). Imaging studies with this
      compound further confirmed that it can be employed to selectively label the human
      beta2-adrenoceptor in single living cells, with receptor-associated binding
      prevented by preincubation with the nonfluorescent beta2-selective antagonist 3
      (isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118551) ( J.
      Cardiovasc. Pharmacol.1983, 5, 430-437. ).

PMID- 21870880
TI  - Synthesis of balsaminone A, a naturally occurring pentacyclic dinaphthofuran
      quinone.
AB  - A short synthesis of the natural product balsaminone A, a dinaphthofuran quinone,
      is described. The key steps of the synthesis are base-induced coupling of 1,4
      dihydroxy-2-naphthaldehyde with 2,3-dichloronaphthoquinone to give a pentacyclic
      dinaphthofuran directly, followed by conversion of the aldehyde into the desired
      methoxy group via the corresponding phenol. The synthesis, in which the structure
      of a key pentacyclic intermediate is corroborated by X-ray crystallography,
      confirms the original structural assignment of the natural product.

PMID- 21870881
TI  - An alpha-diaminoboryl carbanion assisted stereoselective single-pot preparation
      of alpha,beta-disubstituted acrylonitriles.
AB  - An alpha-diaminoboryl carbanion-mediated one-pot olefination directly converts an
      acetonitrile or the homologous nitrile into a series of alpha,beta-disubstituted
      acrylonitriles in a stereoselective manner. The protocol involves the formation
      of an alpha-substituted alpha-diaminoboryl acetonitrile and subsequent
      olefination with an aldehyde. The use of an aryl or conjugated aldehyde
      preferentially leads to a (Z)-acrylonitrile, while an aliphatic aldehyde gave an
      (E)-isomer as a major product. Two complementary approaches, a linear method and
      a divergent method, are developed.

PMID- 21870883
TI  - Coupling of microphase separation and dewetting in weakly segregated diblock co
      polymer ultrathin films.
AB  - We have studied the coupling behavior of microphase separation and autophobic
      dewetting in weakly segregated poly(epsilon-caprolactone)-block-poly(L-lactide)
      (PCL-b-PLLA) diblock co-polymer ultrathin films on carbon-coated mica substrates.
      At temperatures higher than the melting point of the PLLA block, the co-polymer
      forms a lamellar structure in bulk with a long period of L ~ 20 nm, as determined
      using small-angle X-ray scattering. The relaxation procedure of ultrathin films
      with an initial film thickness of h = 10 nm during annealing has been followed by
      atomic force microscopy (AFM). In the experimental temperature range (100-140 
      degrees C), the co-polymer dewets to an ultrathin film of itself at about 5 nm
      because of the strong attraction of both blocks with the substrate. Moreover, the
      dewetting velocity increases with decreasing annealing temperatures. This novel
      dewetting kinetics can be explained by a competition effect of the composition
      fluctuation driven by the microphase separation with the dominated dewetting
      process during the early stage of the annealing process. While dewetting
      dominates the relaxation procedure and leads to the rupture of the ultrathin
      films, the composition fluctuation induced by the microphase separation attempts
      to stabilize them because of the matching of h to the long period (h ~ 1/2L). The
      temperature dependence of these two processes leads to this novel relaxation
      kinetics of co-polymer thin films.

PMID- 21870882
TI  - Proteome of skeletal muscle lipid droplet reveals association with mitochondria
      and apolipoprotein a-I.
AB  - The lipid droplet (LD) is a universal organelle governing the storage and
      turnover of neutral lipids. Mounting evidence indicates that elevated
      intramuscular triglyceride (IMTG) in skeletal muscle LDs is closely associated
      with insulin resistance and Type 2 Diabetes Mellitus (T2DM). Therefore, the
      identification of the skeletal muscle LD proteome will provide some clues to
      dissect the mechanism connecting IMTG with T2DM. In the present work, we
      identified 324 LD-associated proteins in mouse skeletal muscle LDs through mass
      spectrometry analysis. Besides lipid metabolism and membrane traffic proteins, a
      remarkable number of mitochondrial proteins were observed in the skeletal muscle
      LD proteome. Furthermore, imaging by fluorescence microscopy and transmission
      electronic microscopy (TEM) directly demonstrated that mitochondria closely
      adhere to LDs in vivo. Moreover, our results revealed for the first time that
      apolipoprotein A-I (apo A-I), the principal apolipoprotein of high density
      lipoprotein (HDL) particles, was also localized on skeletal muscle LDs. Further
      studies verified that apo A-I was expressed endogenously by skeletal muscle
      cells. In conclusion, we report the protein composition and characterization of
      skeletal muscle LDs and describe a novel LD-associated protein, apo A-I.

PMID- 21870884
TI  - Hibiscus sabdariffa polyphenolic extract inhibits hyperglycemia, hyperlipidemia,
      and glycation-oxidative stress while improving insulin resistance.
AB  - H. sabdariffa polyphenolic extract (HPE) was demonstrated to inhibit high glucose
      stimulated cellular changes. In this study, we analyzed the composition of HPE
      and used a type 2 diabetic rat model to test its protective effect. At least 18
      phenolic compounds were found in HPE. Treatment with HPE reduced hyperglycemia
      and hyperinsulinemia, especially at the dose of 200 mg/kg. HPE decreased serum
      triacylglycerol, cholesterol, and the ratio of low density lipoprotein/high
      density lipoprotein (LDL/HDL). Diabetes promoted plasma advanced glycation end
      product (AGE) formation and lipid peroxidation, while HPE significantly reduced
      these elevations. Immunohistological observation revealed that HPE inhibited the
      expression of connective tissue growth factor (CTGF) and receptor of AGE (RAGE),
      which was increased in type 2 diabetic aortic regions. Furthermore, HPE recovered
      the weight loss found in type 2 diabetic rats. In conclusion, we demonstrated the
      anti-insulin resistance properties of HPE and its effect on hypoglycemia,
      hypolipidemia, and antioxidation. HPE has the potential to be an adjuvant for
      diabetic therapy.

PMID- 21870885
TI  - Environmental comparison of biobased chemicals from glutamic acid with their
      petrochemical equivalents.
AB  - Glutamic acid is an important constituent of waste streams from biofuels
      production. It is an interesting starting material for the synthesis of biobased
      chemicals, thereby decreasing the dependency on fossil fuels. The objective of
      this paper was to compare the environmental impact of four biobased chemicals
      from glutamic acid with their petrochemical equivalents, that is, N
      methylpyrrolidone (NMP), N-vinylpyrrolidone (NVP), acrylonitrile (ACN), and
      succinonitrile (SCN). A consequential life cycle assessment was performed,
      wherein glutamic acid was obtained from sugar beet vinasse. The removed glutamic
      acid was substituted with cane molasses and ureum. The comparison between the
      four biobased and petrochemical products showed that for NMP and NVP the biobased
      version had less impact on the environment, while for ACN and SCN the
      petrochemical version had less impact on the environment. For the latter two an
      optimized scenario was computed, which showed that the process for SCN can be
      improved to a level at which it can compete with the petrochemical process. For
      biobased ACN large improvements are required to make it competitive with its
      petrochemical equivalent. The results of this LCA and the research preceding it
      also show that glutamic acid can be a building block for a variety of molecules
      that are currently produced from petrochemical resources. Currently, most methods
      to produce biobased products are biotechnological processes based on sugar, but
      this paper demonstrates that the use of amino acids from low-value byproducts can
      certainly be a method as well.

PMID- 21870886
TI  - Neuropsychiatric manifestations in systemic lupus erythematosus: epidemiology,
      pathophysiology and management.
AB  - Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease
      with CNS involvement occurring in up to 75% of patients. However, the frequency
      of neuropsychiatric manifestations in SLE studies varies widely, depending on the
      type of manifestations included and the method used for evaluation. CNS
      involvement may be considered primary if directly related to SLE activity in the
      CNS or secondary when related to treatment, infections, metabolic abnormalities
      or other systemic manifestations such as uraemia and hypertension. The
      pathogenesis of neuropsychiatric SLE is as yet unknown, though numerous
      autoantibodies and cytokines have been suggested as possible mediators. However,
      independent of the aetiology of the insult, the final common pathway in
      neuropsychiatric SLE is the involvement of the cerebral microvasculature. The
      diagnosis of primary CNS involvement by SLE is often difficult, as both focal and
      diffuse manifestations may occur and there is no gold standard for diagnosis. A
      high index of clinical suspicion, in addition to laboratory and neuroimaging
      findings may support the diagnosis. Treatment is mostly empirical, although one
      randomized controlled trial has shown that cyclophosphamide in addition to
      methylprednisolone is superior to methylprednisolone alone in severe
      neuropsychiatric SLE.

PMID- 21870887
TI  - Efficacy and tolerability of pharmacotherapies for attention-deficit
      hyperactivity disorder in adults.
AB  - This review examines the evidence regarding the efficacy and tolerability of long
      and short-acting stimulant medications, as well as the non-stimulant medications
      atomoxetine and bupropion in the treatment of adult attention-deficit
      hyperactivity disorder (ADHD). Effect sizes in adults appear to be of almost the
      same magnitude as in school-age children when robust doses are used. There are
      adequate data demonstrating short-term efficacy and safety of medication in ADHD
      during adulthood but long-term studies are lacking, particularly in view of
      concerns regarding cardiovascular adverse events. There is some evidence that
      stimulant medication can improve driving performance in adults with ADHD. The
      extent to which medication may improve academic, occupational and social
      functioning in adults with ADHD is unclear, and future research should
      investigate these outcomes. Medication treatment of adults with ADHD in sports is
      controversial. Both stimulant and non-stimulant medications seem to be well
      tolerated. Monitoring of pulse and blood pressure is recommended with these drugs
      because of their cardiovascular effects. There have been extremely rare case
      reports of sudden death in adults and children treated with stimulants and
      atomoxetine, but it is difficult to clearly establish causality. In view of
      reports of treatment-related suicide-related behaviour with atomoxetine, it is
      recommended that adults should be observed for agitation, irritability, suicidal
      thinking, self-harming or unusual behaviour, particularly in the first months of
      treatment, or after a change of dose. ADHD in adults continues to remain an under
      recognized disorder in many parts of the world and there is a lack of specialist
      clinics for assessment and treatment of adult ADHD. Studies to date have failed
      to show efficacy of medications in the treatment of ADHD in the substance misuse
      population. There is little evidence so far to suggest an increased misuse of
      stimulants or diversion amongst substance misusers; however, data are
      insufficient to draw firm conclusions. Further work is necessary to evaluate
      effective treatments in subgroups such as the substance misuse population, those
      with multiple co-morbidities and different ADHD subtypes.

PMID- 21870888
TI  - Role of serotonin in Alzheimer's disease: a new therapeutic target?
AB  - Mounting evidence accumulated over the past few years indicates that the
      neurotransmitter serotonin plays a significant role in cognition. As a drug
      target, serotonin receptors have received notable attention due in particular to
      the role of several serotonin-receptor subclasses in cognition and memory. The
      intimate anatomical and neurochemical association of the serotonergic system with
      brain areas that regulate memory and learning has directed current drug discovery
      programmes to focus on this system as a major therapeutic drug target. Thus far,
      none of these programmes has yielded unambiguous data that suggest that any of
      the new drug entities possesses disease-modifying properties, and significantly
      more research in this promising area of investigation is required. Compounds are
      currently being investigated for activity against serotonin 5-HT(1), 5-HT(4) and
      5-HT(6) receptors. This review concludes that most work done in the development
      of selective serotonin receptor ligands is in the pre-clinical or early clinical
      phase. Also, while many of these compounds will likely find application as
      adjuvant therapy in the symptomatic treatment of Alzheimer's disease, there are
      currently only a few drug entities with activity against serotonin receptors that
      may offer the potential to alter the progression of the disease.

PMID- 21870890
TI  - Aripiprazole in the treatment of irritability associated with autistic disorder
      in paediatric patients: profile report.

PMID- 21870892
TI  - Evaluation of a pharmacist-managed amiodarone monitoring program.
AB  - BACKGROUND: Because of the potential for serious adverse effects, patients
      treated with amiodarone must be carefully screened and routinely monitored for
      potential liver, thyroid, and pulmonary toxicity. However, laboratory and
      pulmonary monitoring rates have been found to be substantially lower than
      recommended in guidelines, including those of the North American Society of
      Pacing and Electrophysiology (NASPE, 2007). OBJECTIVE: To (a) assess rates of
      laboratory monitoring of liver, thyroid, and pulmonary function and adverse
      events in a pharmacist-managed amiodarone monitoring program compared with usual
      care in an integrated health care system and (b) estimate return on investment
      (ROI) from this intervention. METHODS: This retrospective cohort study used
      clinic and enrollment data to identify those patients in the pharmacist-managed
      program and usual care who received at least 100 days of amiodarone therapy with
      the first prescription for amiodarone (index) from June 1, 2007, through May 31,
      2009 (index date). Laboratory test monitoring was recorded at baseline (up to 6
      months before the index date), from 1-6 months after the index date, 7-12 months
      after the index date, and at any time during the year (months 1-12). Alanine
      aminotransferase (ALT) was evaluated for liver function. Thyroid-stimulating
      hormone (TSH) and, for patients with abnormal TSH ( less than 0.4 micro
      international units [uIU] per mL or greater than 4.0 uIU per mL), free thyroxine
      (T4) were evaluated for thyroid function. Rates of pulmonary function testing
      (PFT) were measured by the diffusion capacity of carbon monoxide tests (DLCO) and
      annual chest x-rays (CXR); electrocardiograms were not counted. Monitoring rates
      were compared using Pearson chi-square tests, and logistic regression was used to
      compare the odds of testing (ALT, TSH, T4, CXR, PFT) between the 2 groups at any
      time during the year after the index date. Concomitant uses of amiodarone with
      high-dose statins and of amiodarone with digoxin were compared using Pearson chi
      square tests. Hospitalizations and emergency room (ER) visits during the 12-month
      follow-up period were counted for (a) interstitial lung disease; (b)
      rhabdomyolysis for patients who received amiodarone with high-dose statins
      (either lovastatin greater than 40 mg per day or greater than 20 mg per day of
      simvastatin or atorvastatin); and (c) for patients with abnormal digoxin, ALT,
      TSH, or T4 levels, if the hospitalization occurred within 2 days of the abnormal
      laboratory value. RESULTS: There were 2,292 patients who received at least 100
      days of amiodarone therapy and met the other inclusion criteria, of whom 181
      patients (7.9%) were in the pharmacist-managed group and 2,111 received usual
      care. There were 90 (49.7%) new amiodarone users in the pharmacist-managed group
      and 990 (46.9%) in usual care. The 2 groups had similar demographic
      characteristics except race, with more whites and fewer African Americans,
      Asians, and Hispanics in usual care. Laboratory monitoring rates for ALT, TSH,
      and T4 were significantly higher in the pharmacist-managed group than usual care
      at the first and second 6 months and at baseline for ALT and TSH but not T4.
      Baseline CXR rates were significantly higher for the pharmacist-managed group
      than usual care (59.1% vs. 49.3%; P=0.011). Few patients in either group received
      PFT tests at baseline, 6.6% versus 3.6% (P=0.042). After controlling for
      covariates (age, gender, race, new vs. continuing use, and comorbidities),
      pharmacist-managed patients were significantly more likely to have at least 1 ALT
      test within the year after the index prescription (odds ratio [OR]=3.13, 95%
      CI=1.12-8.71), as well as a TSH test (OR=8.13, 95% CI=3.27-20.21) and T4
      (OR=2.51, 95% CI=1.67-3.75). PFTs were also more likely to be given to these
      patients (OR=5.89, 95% CI=3.86-8.99). A higher percentage of patients in the
      pharmacist-managed group than in usual care were taking a high-dose statin during
      the 12-month follow-up period (47.5% vs. 36.2%, P=0.003), but of those patients,
      a greater proportion were switched to another statin (14.0% [n=12] vs. 7.5%
      [n=57], P=0.037) or a lower dose (9.3% [n=8] vs. 3.9% [n=30], P=0.022). Six
      patients in the usual care group (0.79% of patients on high-dose statins)
      developed rhabdomyolysis, and 5 (0.24% of all patients in usual care) had an
      admission for interstitial lung disease. The proportions of patients using
      amiodarone and digoxin concomitantly were similar in the 2 groups (35.9% vs.
      31.3%, P=0.197). Among patients with abnormal laboratory results for ALT, TSH,
      and T4, or digoxin, there were 2 all-cause hospitalizations and 1 ER visit in the
      pharmacist-managed group and 34 all-cause hospitalizations and 18 ER visits in
      the usual care group during the follow-up year. Assuming that all
      hospitalizations and ER visits incurred in the usual care group were avoid- able,
      approximately $2.14 could be saved for every dollar spent on the pharmacist
      managed amiodarone monitoring program. CONCLUSIONS: Pharmacist management of
      patients treated with amiodarone was associated with improved monitoring of
      recommended laboratory tests and PFTs.

PMID- 21870889
TI  - Targeting progressive neuroaxonal injury: lessons from multiple sclerosis.
AB  - Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease
      (PD) and amyotrophic lateral sclerosis (ALS), are characterized by progressive
      neuroaxonal injury, suggesting a common pathophysiological pathway.
      Identification and development of neuroprotective therapies for such diseases has
      proven a major challenge, particularly because of an already substantial
      neuroaxonal compromise at the time of initial onset of clinical symptoms. Methods
      for early identification of neurodegeneration are therefore vital to ensure that
      neuroprotective therapies are applied as early as possible. Recent investigations
      have enhanced our understanding of the role of neuroaxonal injury in multiple
      sclerosis (MS). As MS generally manifests earlier in life and can be diagnosed
      much earlier in the course of the disease than the above-mentioned 'classic'
      neurodegenerative diseases, it is possible that MS could be used as a model
      disease to study degeneration and regeneration of the CNS. The mechanism of
      neuroaxonal injury in MS is believed to be inflammation-led neurodegeneration;
      however, the reverse may also be true (i.e. neuroaxonal degeneration may precede
      inflammation). Animal models of PD, AD and ALS have shown that it is likely that
      most cases of disease are due to initial inflammation, followed by a degenerative
      process, providing a parallel between MS and the classic neurodegenerative
      diseases. Other common factors between MS and the neurodegenerative diseases
      include iron and mitochondrial dysregulation, abnormalities in alpha-synuclein
      and tau protein, and a number of immune mediators. Conventional MRI techniques,
      using markers such as T2-weighted lesions, gadolinium-enhancing lesions and T1
      weighted hypointensities, are readily available and routinely used in clinical
      practice; however, the utility of these MRI measures to predict disease
      progression in MS is limited. More recently, MRI techniques that provide more
      pathology-specific data have been applied in MS studies, including magnetic
      resonance spectroscopy, magnetization transfer ratio and myelin water imaging.
      Optical coherence tomography (OCT) is a non-MRI technique that quantifies optic
      nerve integrity and retinal ganglion cell loss as markers of neuroaxonal injury;
      more research is needed to evaluate whether information obtained from OCT is a
      reliable marker of axonal injury and long-term disability in MS. Using these
      advanced techniques, it may become possible to follow degeneration and
      regeneration longitudinally in patients with MS and to better differentiate the
      effects of drugs under investigation. Currently available immune-directed
      therapies that are approved by the US FDA for the first-line treatment of MS
      (interferon-beta and glatiramer acetate) have been shown to decelerate the
      inflammatory process in MS; however, such therapy is less effective in preventing
      the progression of the disease and neuroaxonal injury. The use of MS as a
      clinical model to study modulation of neuroaxonal injury in the brain could have
      direct implications for the development of treatment strategies in
      neurodegenerative diseases such as AD, PD and ALS.

PMID- 21870891
TI  - Quetiapine extended release: adjunctive treatment in major depressive disorder.
AB  - Quetiapine extended release (XR) is a once-daily oral formulation of the atypical
      antipsychotic quetiapine that is available for use as adjunctive therapy in major
      depressive disorder (MDD). Systemic quetiapine exposure after orally administered
      quetiapine XR is similar to that of quetiapine immediate release at the same
      dosage, although quetiapine XR is absorbed more slowly and plasma concentrations
      are more stable over time. In two 6-week, randomized, double-blind, placebo
      controlled, multinational trials in patients with MDD with an inadequate response
      to antidepressants, quetiapine XR 300 mg/day adjunctive to antidepressant reduced
      depressive symptoms significantly more than antidepressant plus placebo,
      according to changes in Montgomery-Asberg Depression Rating Scale (MADRS) total
      scores. In one trial, adjunctive quetiapine XR 150 mg/day also led to
      significantly greater reductions in MADRS total scores than antidepressant plus
      placebo. MDD response rates were significantly higher with adjunctive quetiapine
      XR 300 mg/day (but not 150 mg/day) than with antidepressant plus placebo. The
      numbers needed to treat to achieve an additional response over antidepressant
      plus placebo were 11-18 and 8-9 in the quetiapine XR 150 and 300 mg/day dosage
      groups, respectively. Treatment-emergent adverse events were mostly of mild to
      moderate severity; 1% of adjunctive quetiapine XR and 1.3% of antidepressant plus
      placebo recipients reported serious adverse events.

PMID- 21870893
TI  - Effect of chronic kidney disease on warfarin management in a pharmacist-managed
      anticoagulation clinic.
AB  - BACKGROUND: There is growing evidence that kidney disease affects hepatically
      cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD)
      would disrupt anticoagulation of warfarin-treated patients and thereby increase
      the amount of management required to maintain appropriate anticoagulation.
      Specifically, we anticipated that more dose manipulations (both dose changes and
      transient dose adjustments) and shorter times between scheduled clinic visits
      would be required for anticoagulation patients with CKD. OBJECTIVES: To determine
      how CKD affected warfarin maintenance dose, anticoagulation stability, the
      proportion of clinic visits that necessitated a dose manipulation (either a
      change in the prescribed weekly dose or a transient dose adjustment), and the
      length of time between scheduled visits in 2 pharmacist-managed anticoagulation
      clinics. METHODS: Our retrospective, cohort chart review investigated warfarin
      response in anticoagulation clinic patients. From the clinic database of patients
      with an international normalized ratio (INR) target range of 2.0-3.0, we matched
      20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per
      minute) to 20 comparison group patients (estimated creatinine clearance greater
      than 60 mL per minute) based on parameters demonstrated to affect warfarin dose:
      ethnicity, gender, age, body surface area, and simvastatin use. We calculated the
      average weekly dose used to maintain target INR (assessment period range=116
      1,408 days). To evaluate anticoagulation stability and patient management, we
      quantified several parameters, including the percentage of total time in
      therapeutic range, the proportion of clinic visits that required a dose change,
      and the time between scheduled visits. We compared group means using t-tests, and
      categorical data were compared using Fisher's exact test. RESULTS: Our population
      was predominantly female (75%) and of African ancestry (95%); average age 60
      years. Patients with CKD required a 24% lower dose than the comparison group
      (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time
      in therapeutic range required increased clinic management versus the comparison
      group, as indicated by a significantly higher proportion of clinic visits at
      which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between
      scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively,
      P=0.001). CONCLUSIONS: CKD was associated with both decreased warfarin
      maintenance dose and decreased anticoagulation stability which, in turn, required
      more frequent and intensive anticoagulation clinic management.

PMID- 21870894
TI  - All-cause and incremental per patient per year cost associated with chronic
      hepatitis C virus and associated liver complications in the United States: a
      managed care perspective.
AB  - BACKGROUND: Approximately 3.2-3.9 million U.S. residents are infected with the
      hepatitis C virus (HCV). Total annual costs (direct and indirect) in the United
      States for HCV were estimated to be $5.46 billion in 1997, and direct medical
      costs have been predicted to increase to $10.7 billion for the 10-year period
      from 2010 through 2019, due in part to the increasing number of HCV patients
      developing advanced liver disease (AdvLD). OBJECTIVE: To quantify in a sample of
      commercially insured enrollees (a) total per patient per year (PPPY) all-cause
      costs to the payer, overall and by the stage of liver disease, for patients
      diagnosed with HCV; and (b) incremental all-cause costs for patients diagnosed
      with HCV relative to a matched non-HCV cohort. METHODS: This retrospective,
      matched cohort study included patients aged at least 18 years and with at least 6
      months of continuous enrollment in a large managed care organization (MCO) claims
      database from July 1, 2001, through March 31, 2010. Patients with a diagnosis of
      HCV (ICD-9-CM codes 070.54, 070.70) were identified and stratified into those
      with and without AdvLD, defined as decompensated cirrhosis (ICD-9-CM codes
      070.44, 070.71, 348.3x, 456.0, 456.1, 456.2x, 572.2, 572.3, 572.4, 782.4,
      789.59); hepatocellular carcinoma (HCC, ICD-9-CM code 155); or liver transplant
      (ICD-9-CM codes V42.7, 50.5 or CPT codes 47135, 47136). For patients without
      AdvLD, the index date was the first HCV diagnosis date observed at least 6 months
      after the first enrollment date, and at least 6 months of continuous enrollment
      after the index date were required. HCV patients without AdvLD were stratified
      into those with and without compensated cirrhosis (ICD-9-CM codes 571.2, 571.5,
      571.6). For patients with AdvLD, the index date was the date of the first AdvLD
      diagnosis observed at least 6 months after the first enrollment date, and at
      least 1 day of enrollment after the index date was required. Cases were matched
      in an approximate 1:10 ratio to comparison patients without an HCV diagnosis or
      AdvLD diagnosis who met all other inclusion criteria based on gender, age,
      hospital referral region state, pre-index health care costs, alcoholism, human
      immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and a
      modified Charlson Comorbidity Index. For the HCV and comparison patient cohorts,
      PPPY all-cause costs to the payer were calculated as total allowed charges summed
      across all patients divided by total patient-days of follow-up for the cohort,
      multiplied by 365, inflation-normalized to 2009 dollars. Because the calculation
      of PPPY cost generated a single value for each cohort, bootstrapping was used to
      generate descriptive statistics. Incremental PPPY costs for HCV patients relative
      to non-HCV patients were calculated as between-group differences in PPPY costs. T
      tests for independent samples were used to compare costs between case and
      comparison cohorts. RESULTS: A total of 34,597 patients diagnosed with HCV, 78.0%
      with HCV without AdvLD, 4.4% with compensated cirrhosis, 12.3% with decompensated
      cirrhosis, 2.8% with HCC, and 2.6% with liver transplant, were matched to 330,435
      comparison patients. Mean (SD) age of all HCV cases was 49.9 (8.5) years; 61.7%
      were male. Incremental mean (SD) PPPY costs in 2009 dollars for all HCV patients
      relative to comparison patients were $ 9,681 ($176) PPPY. Incremental PPPY costs
      were $5,870 ($157) and $5,330 ($491) for HCV patients without liver disease and
      with compensated cirrhosis, respectively. Incremental PPPY costs for patients
      with AdvLD were $27,845 ($ 965) for decompensated cirrhosis, $43,671 ($2,588) for
      HCC, and $ 93,609 ($4,482) for transplant. Incremental prescription drug costs,
      including the cost of antiviral drugs, were $2,739 ($37) for HCV patients
      overall, $2,659 ($41) for HCV without liver involvement, and $3,102 ($157) for
      HCV with compensated cirrhosis. These between-group differences were
      statistically significant at P<0.001. CONCLUSIONS: Based on a retrospective
      analysis of data from a large, MCO claims database, patients diagnosed with HCV
      had annual all-cause medical costs that were almost twice as high as those of
      enrollees without a diagnosis of HCV. Health care costs increased dramatically
      with AdvLD. Data from this study may help MCOs project future HCV costs and
      facilitate planning for HCV patient management efforts.

PMID- 21870895
TI  - Do triptan antimigraine medications interact with SSRI/SNRI antidepressants? What
      does your decision support system say?

PMID- 21870896
TI  - Functional characterization of drug uptake and metabolism in the heart.
AB  - INTRODUCTION: Evaluation of kinetics of uptake into the heart could be important
      for the efficacy and toxicity of cardioactive drugs. Although recent advances in
      molecular biology have identified cardiac uptake and efflux transporters as well
      as drug-metabolizing enzymes, little is known about their functional properties
      in situ. AREAS COVERED: The modeling of cardiac pharmacokinetics and
      pharmacodynamics (PK/PD) is overviewed with respect to experimental designs. Also
      covered is the role of myocardial uptake and binding processes for pharmacologic
      effect kinetics in relation to cardiac drugs. An update is given on the role of
      transport processes for the acute myocardial uptake of drugs and the impact on
      the time course of pharmacodynamic effects, as well as the interaction of drugs
      with CYP enzymes in myocytes. EXPERT OPINION: Depending on physicochemical
      properties, drugs are relatively rapidly taken up by the heart. It is important
      to realize that interstitial concentration is determinative when cardiac drugs
      act via cell membrane receptors. The role of uptake and efflux transporters in
      myocardial uptake of drugs is not yet clearly defined. Kinetic modeling of
      receptor-mediated pharmacodynamics may provide useful information on receptor
      binding and transduction processes. Inhibition or induction of cardiac CYP by
      drugs can cause changes in the metabolism of endogenous substances and thus
      influence cardiac function.

PMID- 21870897
TI  - Pharmacokinetic evaluation of vadimezan (ASA404, 5,6-dimethylxanthenone-4-acetic
      acid, DMXAA).
AB  - INTRODUCTION: Understanding the pharmacokinetics (PK) and pharmacodynamics of a
      drug is important to optimizing its use. Vadimezan is a tumor vascular-disrupting
      agent that acutely disrupts blood flow within tumors and induces innate tumor
      immunity. It has enhanced the activity of anticancer treatments in preclinical
      models and early phase trials, although one Phase III trial result was negative
      and another is yet to be reported. AREAS COVERED: Areas covered in this review
      are the preclinical and human PK and the inter-relationship among PK, toxicity
      and efficacy of vadimezan as a single agent and in combination with other
      therapies. These data are derived from a literature search on Medline and also
      from conference proceedings, abstracts and trial reports available up to June
      2011. EXPERT OPINION: The disappointing results of one Phase III trial, despite
      the promising randomized Phase II trial data, highlight the challenges in
      translational research, especially in selecting the optimal development strategy.
      This paper discusses how different scheduling of vadimezan could significantly
      enhance the anticancer efficacy of this drug in combination with other therapies,
      especially those that do not require concurrent corticosteroid administration.

PMID- 21870898
TI  - Adenosine triphosphate-dependent calcium signaling during ventilator-induced lung
      injury is amplified by hypercapnia.
AB  - Adenosine triphosphate (ATP) is released by alveolar epithelial cells during
      ventilator-induced lung injury (VILI) and regulates fluid transport across
      epithelia. High CO(2) levels are observed in patients with "permissive
      hypercapnia," which inhibits alveolar fluid reabsorption (AFR) in alveolar
      epithelial cells. The authors set out to determine whether VILI affects AFR and
      whether the purinergic pathway is modulated in cells exposed to hypercapnia.
      Control group was compared against VILI (tidal volume [Vt] = 35 mL/kg, zero
      positive end-expiratory pressure [PEEP]) and protective ventilation (Vt = 6
      mL/kg, PEEP = 10 cm H(2)O) groups. Lung mechanics, histology, and AFR were
      evaluated. Alveolar epithelial cells (AECs) were loaded with Fura 2-AM to measure
      intracellular calcium in the presence ATP (10 MUM) at 5% or 10% CO(2) as compared
      with baseline. High tidal volume ventilation impairs lung mechanics and AFR.
      Hypercapnia (HC) increases intracellular calcium levels in response to ATP
      stimulation. HC + ATP is the most detrimental combination decreasing AFR.
      Purinergic signaling in AECs is modulated by high CO(2) levels via increased
      cytosolic calcium. The authors reason that this modulation may play a role in the
      impairment of alveolar epithelial functions induced by hypercapnia.

PMID- 21870899
TI  - Discontinued drugs in 2010: cardiovascular drugs.
AB  - This perspective is a paper discussing drugs dropped from clinical development in
      the previous years. Specifically, this paper focuses on 16 cardiovascular drugs
      discontinued in 2010 after reaching Phase I - III clinical trials. Information
      for this perspective is mainly derived from a search of Pharmaprojects.

PMID- 21870900
TI  - Robotic gait training in patients with impaired consciousness due to severe
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This prospective controlled non-randomized study investigated
      the effects of robotic gait training on electroencephalographic (EEG) brain
      activity in patients with impaired consciousness due to severe traumatic brain
      injury (TBI). METHODS: Twelve TBI patients and 14 healthy controls underwent a
      single training session on a computer-driven gait orthosis (Lokomat(r)). The
      sensory pathways were assessed using sensory evoked potentials (SEPs). The global
      delta-alpha EEG power ratio (DAR) and latency of the P300 component of the event
      related potentials was assessed prior to and following a training session.
      RESULTS: Baseline measurements showed impaired SEPs in the majority of patients
      and significantly larger DAR in patients compared to healthy controls. Robotic
      gait training resulted in a reduction of the DAR in healthy subjects but not in
      patients. No changes were observed in P300 latencies after training in either
      patients or healthy controls. CONCLUSION: The study showed that robotic gait
      training induced measurable changes in the EEG power spectrum in healthy
      individuals, while no changes were observed in patients with severe TBI. The
      absence of the EEG changes following training might be an indicator of the
      severity of brain dysfunction.

PMID- 21870901
TI  - Axis I and II psychiatric disorders in patients with traumatic brain injury: a 12
      month follow-up study.
AB  - OBJECTIVE: To evaluate the occurrence of axis I and II psychiatric disorders
      among patients with traumatic brain injury (TBI). DESIGN: Prospective
      observational study. Forty-five adult patients, who had attended an emergency
      unit because of TBI, were recruited. At 12 months, 38 patients were interviewed.
      MEASURES: Psychiatric disorders were evaluated using the Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN) and the Structured Clinical Interview for
      DSM-IV Personality Disorders (SCID-II). RESULTS: Before TBI, the 12-month rate of
      axis I psychiatric disorders was relatively high (39.5%) and the rate of alcohol
      dependence was especially elevated (18.4%). During the 12 months after TBI, axis
      I disorders were found in 47.4% of subjects. Six patients (15.8%) were found to
      have a disorder with an onset after TBI. Of these, five patients had depressive
      disorders (13.2%). Almost one third of the subjects (29.0%) had personality
      disorders. Antisocial and obsessive-compulsive personality disorders were the
      most frequent (10.5%). CONCLUSIONS: Both axis I and II psychiatric disorders are
      common among patients with TBI. Alcohol dependence and personality disorders are
      prevalent in individuals prone to TBI, whereas depressive disorders typically
      develop after injury. Psychiatric disorders should be addressed in
      rehabilitation, as otherwise they will hinder the recovery after TBI.

PMID- 21870902
TI  - Acquired brain injury secondary to systemic sclerosis: a case report.
AB  - STUDY DESIGN: Case report. BACKGROUND: Systemic sclerosis is a rare and chronic
      autoimmune disease of the body's connective tissue that historically has not been
      associated with primary involvement of the central nervous system. OBJECTIVE: To
      describe the neuropsychological sequelae of systemic sclerosis in a 56-year-old
      male. RESULTS: Neurocognitive deficits were demonstrated by the patient on select
      components of memory and language as well as across measures of executive
      functioning. Significant depression and reduced self-concept were also
      identified. DISCUSSION: Neuropsychological dysfunction in patients with systemic
      sclerosis has largely been ignored in the clinical setting. Identification of
      neurocognitive impairment and emotional stress can facilitate interventions that
      consequently may increase adherence with medical treatment and increase quality
      of-life.

PMID- 21870903
TI  - Associations between illness perceptions, coping styles and outcome after mild
      traumatic brain injury: preliminary results from a cohort study.
AB  - PURPOSE: The objective of this study was to examine associations between injury
      perceptions, coping, distress and outcome after mild traumatic brain injury
      (MTBI). DESIGN: A prospective observational study with repeated measures. This
      study reports results from the first of two study visits. PARTICIPANTS:
      Participants (n = 147) were recruited within 3 months following presentation to a
      concussion clinic or an emergency department setting. METHODS: Clinical and
      demographic information was collected and participants completed a range of
      questionnaires (Revised Illness Perceptions Questionnaire, Brief COPE, Rivermead
      Post-Concussion Symptoms Questionnaire, Rivermead Follow-Up Questionnaire and
      HADS). Associations between independent variables and outcome were examined using
      odds ratios and 95% confidence intervals. RESULTS: Preliminary results suggested
      participants endorsing stronger beliefs about the injury identity (p < 0.05) and
      emotional impact (p < 0.01) had significantly greater odds of poor outcome at 3
      months. There were also associations between higher educational attainment (p <
      0.05), using active coping strategies (p < 0.06) and poor outcome. CONCLUSIONS:
      These variables appeared important determinants of outcome early after MTBI and
      may help identify those at risk for slow recovery. Current reassurance-based
      interventions may be improved by targeting such variables.

PMID- 21870904
TI  - A case of Sweet's syndrome due to 5-Azacytidine and vorinostat in a patient with
      NK/T cell lymphoma.

PMID- 21870905
TI  - Development of enteric submicron particles formulation of alpha-amylase for oral
      delivery.
AB  - Enteric submicron particles (SPs) formulations of alpha-amylase were prepared by
      w/o/w emulsion solvent evaporation using hydroxypropyl methylcellulose phthalate
      (HPMCP) and Eudragit L 100, to avoid gastric inactivation of alpha-amylase.
      Smaller internal and external aqueous phase volume provided maximum encapsulation
      efficiency (71.92-73.40%), least particle size (546.4-595.4 nm) and 23-26% loss
      of enzyme activity. Release studies in 0.1 N HCl confirmed the gastro-resistance
      of formulations. The anionic SPs aggregated in 0.1 N HCl (i.e. gastric pH 1.2),
      due to protonation of carboxylic groups of enteric polymer. The aggregates being
      < 500 um size would not impede gastric emptying. However, at pH >5.0 (duodenal
      pH), SPs showed de-aggregation due to restoration of surface charge. HPMCP and
      Eudragit L 100 SPs facilitated almost complete release of alpha-amylase within 30
      min at pH 6.0 and 6.8, respectively, following Higuchi kinetics. PXRD and DSC
      indicated amorphous character and scanning electron microscope showed spherical
      shape of SPs. In simulated gastro-intestinal pH condition, HPMCP and Eudragit L
      100 SPs showed good digestion of cooked rice and could serve as potential carrier
      for oral enzyme delivery. Stability studies indicated the formulations as quite
      stable to ensure 2 years shelf life at room temperature.

PMID- 21870906
TI  - The effect of red clover isoflavone supplementation over vasomotor and menopausal
      symptoms in postmenopausal women.
AB  - OBJECTIVE: To evaluate the effect of red clover isoflavone supplementation over
      vasomotor and overall menopausal symptoms in postmenopausal women. METHODS: One
      hundred and nine postmenopausal women aged 40 or more were assigned to randomly
      receive either two daily capsules of the active compound (80 mg red clover
      isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day
      period. After a washout period of 7 days, medication was crossed over and taken
      for 90 days more. Daily hot flush and night sweat frequency and overall
      menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97
      and 187 days. RESULTS: Daily hot flush/night sweat frequency and Kupperman Index
      values were similar in both studied groups at baseline. All indices significantly
      decreased after red clover phase in Group A, corresponding, respectively to a
      73.5%, 72.2% and 75.4% average decrement. These decrements were significantly
      higher than those observed for Group B after placebo phase (8.2%, 0.9% and 6.7%
      respectively). In Group A, after washout and placebo phases all values
      significantly increased. In Group B, all indices remained similar after placebo
      and washout phases, however significantly dropping after red clover treatment.
      These values were also significantly lower than those observed in Group A after
      placebo phase. No side effects were encountered after treatment with the active
      compound or placebo. CONCLUSION: Red clover isoflavone supplementation was more
      effective than placebo in reducing daily vasomotor frequency and overall
      menopausal intensity in postmenopausal women.

PMID- 21870907
TI  - Association between eight adiponectin polymorphisms, obesity, and metabolic
      syndrome parameters in Tunisian volunteers.
AB  - BACKGROUND: Adiponectin is a plasma protein produced by the adipose tissue, with
      insulin sensibility, antiinflammatory and antiatherogenic properties. Many
      adiponectin gene polymorphisms have been described, and their implication in
      obesity, metabolic syndrome, and cardiovascular diseases was controversial. Our
      aim was to study the relationship between eight adiponectin polymorphisms (
      1391G/A, -1377C/G, 4522C/T, 395 G/A, 276G/T, 639C/T, 45T/G, and +2019delA),
      metabolic syndrome parameters, and the risk of obesity in Tunisian volunteers.
      METHODS: We have recruited 169 nonobese [sex ratio=0.594, mean age 43.25+/-13.12
      years; mean body mass index (BMI) 24.73+/-3.50 kg/m(2)] and 160 obese (BMI>=30
      kg/m(2)) (sex ratio=0.221, mean age 48.41+/-10.92 years; mean BMI 36.6+/-4.8
      kg/m(2)). Genotyping was performed using polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP). Glucose, insulin, and lipids were
      measured. BMI and homeostasis model assessment of insulin resistance (HOMA-IR)
      were calculated. RESULTS: The polymorphisms 276G/T, 639 C/T, 11391 G/A, 11374C/G,
      and +2019delA seem to contribute to obesity. In fact, adjusted odds ratios (ORs)
      of obesity associated with mutated genotypes of each polymorphism were,
      respectively: OR=0.64, P=0.039; OR=1.85, P=0.018; OR=1.68, P=0.044; OR=1.77,
      P=0.038; and OR=1.94, P=0.010). Mutated genotypes at 639 C/T were associated with
      higher waist circumference, BMI, and systolic and diastolic blood pressure. In
      addition, the 11391AA genotype was associated with increased BMI. Concerning
      2019delA, the delAdelA genotype was associated with increased HOMA-IR and BMI,
      suggesting a possible effect of these single-nucleotide polymorphisms (SNPs) on
      insulin resistance parameters. Mutated genotypes at 276G/T were associated with
      lower serum insulin concentration and lower systolic and diastolic blood
      pressure. The other genotypes showed no association with metabolic syndrome
      parameters. CONCLUSION: Adiponectin gene polymorphisms were associated with
      obesity and metabolic syndrome parameters in Tunisian volunteers.

PMID- 21870909
TI  - Manneristic behaviors of visually impaired children.
AB  - AIM: To review the literature on visual impairment in children in order to
      determine which manneristic behaviors are associated with visual impairment, and
      to establish why these behaviors occur and whether severity of visual impairment
      influences these behaviors. METHODS: A literature search utilizing PubMed, OVID,
      Google Scholar, and Web of Knowledge databases was performed. The University of
      Liverpool ( www.liv.ac.uk/orthoptics/research ) and local library facilities were
      also searched. RESULTS: The main manneristic or stereotypic behaviors associated
      with visual impairment are eye-manipulatory behaviors, such as eye poking and
      rocking. The degree of visual impairment influences the type of behavior
      exhibited by visually impaired children. Totally blind children are more likely
      to adopt body and head movements whereas sight-impaired children tend to adopt
      eye-manipulatory behaviors and rocking. The mannerisms exhibited most frequently
      are those that provide a specific stimulation to the child. Theories to explain
      these behaviors include behavioral, developmental, functional, and
      neurobiological approaches. Although the precise etiology of these behaviors is
      unknown, it is recognized that each of the theories is useful in providing some
      explanation of why certain behaviors may occur. The age at which the frequency of
      these behaviors decreases is associated with the child's increasing development,
      thus those visually impaired children with additional disabilities, whose
      development is impaired, are at an increased risk of developing and maintaining
      these behaviors. Certain manneristic behaviors of the visually impaired child may
      also help indicate the cause of visual impairment. CONCLUSIONS: There is a wide
      range of manneristic behaviors exhibited by visually impaired children. Some of
      these behaviors appear to be particularly associated with certain causes of
      visual impairment or severity of visual impairment, thus they may supply the
      practitioner with useful information. Further research into the prevalence of
      these behaviors in the visually impaired child is required in order to provide
      effective management.

PMID- 21870908
TI  - Evaluation of CeolusTM microcrystalline cellulose grades for the direct
      compression of enteric-coated pellets.
AB  - The preparation of multiparticulate tablets by direct compression of functionally
      coated pellets is technologically challenging. The objective was to investigate
      the influence of different grades of microcrystalline cellulose (CeolusTM UF-711,
      PH-102, PH-200 and KG-802) as fillers on the properties of blends and tablets
      containing enteric pellets. CelphereTM spheres were drug-layered and then
      functionally coated with Eudragit((r)) L 30 D-55/FS 30D dispersion. Tablets
      loaded with 50% pellets were prepared using pure or binary blends of
      microcrystalline cellulose fillers. The influence of the filler on the blend
      flow, segregation tendency, tablet hardness and enteric release properties were
      studied using a mixture design, and the optimum filler composition was
      determined. Rapidly disintegrating tablets, which yielded a drug release of less
      than 10% after 2 hours in acidic medium, could be successfully prepared. The
      blend composition had a significant effect on the flowability, but less on the
      tablet hardness which was influenced by the selection of lubricant. Blends
      containing celluloses with low bulk densities exhibited a reduced tendency to
      segregate. Pellet distribution uniformity was further improved when using
      CeolusTM UF-711 blended with a high-density grade. As a conclusion,
      multiparticulate tablets containing enteric pellets with preserved delayed
      release properties were successfully prepared using CeolusTM microcrystalline
      celluloses as tableting excipients. The optimized filler blend for the direct
      compression of 50% enteric pellets into tablets contained CeolusTM UF-711 as main
      component in combination with CeolusTM PH-200.

PMID- 21870910
TI  - 5 years on.

PMID- 21870911
TI  - Experimental models of amblyopia: insights for prevention and treatment.
AB  - Human amblyopia has been modeled in a number of mammalian species in
      physiological, anatomical and behavioral terms for nearly 50 years, and insights
      from these studies have both offered explanations of observations made in humans
      and resulted in improved prevention and refined treatment. In recent years,
      animal models of part-time daily monocular deprivation have made an important
      contribution to the occlusion therapy of amblyopia in children.

PMID- 21870912
TI  - Amblyopia therapy: an update.
AB  - We review the findings of trials of mainstay amblyopia treatment conducted within
      the last 5 years. These have confirmed that an initial period of full-time
      refractive correction is beneficial in all types of amblyopia. Adopting this
      practice may allow up to 30% of children to avoid any further treatment. Studies
      that have investigated the role of atropine occlusion as a first-line treatment
      for amblyopia have shown "weekend atropine" to be as effective as patching for
      children with both moderate and severe amblyopia. Where patching is prescribed, 2
      4 hours/day of occlusion appears sufficient to provide an optimum outcome for the
      majority of children, although those over 6 years tend to require a larger dose
      to achieve best outcome, their amblyopia being more resistant to treatment.
      Educational interventions such as cartoons and written and video explanations of
      treatment aimed at improving compliance appear to raise it to a therapeutic level
      in those who may otherwise have poor compliance or drop out from treatment.
      Formal, evidence-based practice guidelines for the management of amblyopia have
      emerged although their adoption by practitioners, at least in the United Kingdom,
      has been questioned.

PMID- 21870914
TI  - Restoration of binocular vision in amblyopia.
AB  - PURPOSE: To develop a treatment for amblyopia based on re-establishing binocular
      vision. METHODS: A novel procedure is outlined for measuring and reducing the
      extent to which the fixing eye suppresses the fellow amblyopic eye in adults with
      amblyopia. We hypothesize that suppression renders a structurally binocular
      system, functionally monocular. RESULTS: We demonstrate that strabismic amblyopes
      can combine information normally between their eyes under viewing conditions
      where suppression is reduced by presenting stimuli of different contrast to each
      eye. Furthermore we show that prolonged periods of binocular combination leads to
      a strengthening of binocular vision in strabismic amblyopes and eventual
      combination of binocular information under natural viewing conditions (stimuli of
      the same contrast in each eye). Concomitant improvement in monocular acuity of
      the amblyopic eye occurs with this reduction in suppression and strengthening of
      binocular fusion. Additionally, stereoscopic function was established in the
      majority of patients tested. We have implemented this approach on a headmounted
      device as well as on a handheld iPod. CONCLUSION: This provides the basis for a
      new treatment of amblyopia, one that is purely binocular and aimed at reducing
      suppression as a first step.

PMID- 21870913
TI  - Can human amblyopia be treated in adulthood?
AB  - Amblyopia is a common visual disorder that results in a spatial acuity deficit in
      the affected eye. Orthodox treatment is to occlude the unaffected eye for lengthy
      periods, largely determined by the severity of the visual deficit at diagnosis.
      Although this treatment is not without its problems (poor compliance, potential
      to reduce binocular function, etc) it is effective in many children with moderate
      to severe amblyopia. Diagnosis and initiation of treatment early in life are
      thought to be critical to the success of this form of therapy. Occlusion is
      rarely undertaken in older children (more than 10 years old) as the visual
      benefits are considered to be marginal. Therefore, in subjects where occlusion is
      not effective or those missed by mass screening programs, there is no alternative
      therapy available later in life. More recently, burgeoning evidence has begun to
      reveal previously unrecognized levels of residual neural plasticity in the adult
      brain and scientists have developed new genetic, pharmacological, and behavioral
      interventions to activate these latent mechanisms in order to harness their
      potential for visual recovery. Prominent amongst these is the concept of
      perceptual learning--the fact that repeatedly practicing a challenging visual
      task leads to substantial and enduring improvements in visual performance over
      time. In the normal visual system the improvements are highly specific to the
      attributes of the trained stimulus. However, in the amblyopic visual system,
      learned improvements have been shown to generalize to novel tasks. In this paper
      we ask whether amblyopic deficits can be reduced in adulthood and explore the
      pattern of transfer of learned improvements. We also show that developing
      training protocols that target the deficit in stereo acuity allows the recovery
      of normal stereo function even in adulthood. This information will help guide
      further development of learning-based interventions in this clinical group.

PMID- 21870916
TI  - Dissertation on various accidents of sight.

PMID- 21870915
TI  - Amblyopia and real-world visuomotor tasks.
AB  - A question of increasing interest to the basic science and clinical management
      communities during the past decade is whether children and adults with amblyopia
      and associated binocular visual abnormalities experience difficulties in
      executing real-world actions, to which vision normally makes an important
      functional contribution. Here we provide objective evidence that they do, by
      reviewing quantitative data from a number of studies comparing their performance
      with that of matched normally sighted subjects on a range of everyday visuomotor
      tasks. Because in real life, these tasks (grasping objects, walking, driving,
      reading) are habitually performed with both eyes open, our focus is on their
      binocular skill deficits, rather than those with their amblyopic eye alone.
      General findings are that individuals with abnormal binocularity show impairments
      in critical aspects of motor control--movement speed, accuracy or both--on every
      one of these activities, the extent of which correlates with their loss of
      stereoacuity, but not the severity of their amblyopia. Impairments were
      especially marked when the task was time-limited or novel. Implications are that
      children and adults with severely reduced or absent binocularity may be accident
      prone when required to respond rapidly to unexpected situations and that
      amblyopia management should focus more attention on evaluating and restoring
      stereoacuity and stereomotion processing.

PMID- 21870918
TI  - ANZJP this month.

PMID- 21870919
TI  - Problems with suicide risk assessment.

PMID- 21870920
TI  - Childhood adversity, trauma and abuse: context and consequences.

PMID- 21870921
TI  - Fields of interest and influence: a new method for sourcing and ranking journals
      in psychiatry.

PMID- 21870922
TI  - Atypical antipsychotics cause an acute increase in cutaneous hand blood flow in
      patients with schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: Clinical studies suggest resting thermoregulatory cutaneous vasomotor
      tone could be increased in schizophrenia, resulting in reduced hand blood flow.
      In animal models, atypical antipsychotics including clozapine potently inhibit
      sympathetic neural outflow to the thermoregulatory cutaneous vascular beds. We
      have now determined whether antipsychotic medication administration is associated
      with an acute increase in hand blood flow in patients with schizophrenia and
      schizoaffective disorder, and whether this increase correlates with clinical
      status. METHOD: Hand temperature was measured with an infrared camera in 12
      patients with chronic schizophrenia or schizoaffective disorder 30 min prior to,
      then 30 and 60 min following medication. Clinical status was assessed via the
      Brief Psychiatric Rating Scale (BPRS). Results were compared using regression and
      repeated measures analysis of variance. RESULTS: A robust and significant
      increase in hand temperature (p < 0.001) was observed following antipsychotic
      administration. The mean increase after 60 min was 4.1 +/- 2.4 degrees C. This
      increase was significantly associated with colder hand temperature prior to
      medication (p < 0.05; suggestive of increased resting vasoconstriction) and with
      more severe psychiatric symptoms (p < 0.05). CONCLUSIONS: Atypical antipsychotics
      were associated with increased hand blood flow, consistent with inhibition of
      thermoregulatory sympathetic outflow to the cutaneous vascular bed in patients
      with schizophrenia and schizoaffective disorder. This increase correlated with
      symptom severity. Hand temperature increase following antipsychotic medication
      may therefore be a simple and informative physiological marker of disease
      activity and potential response in patients with schizophreniform disorders.
      Given that antipsychotics also inhibit sympathetic outflow to brown adipose
      tissue, which normally converts energy to heat, future studies should examine
      whether antipsychotic-induced hand temperature increase is associated with
      antipsychotic-induced weight gain.

PMID- 21870923
TI  - 13 year follow up of morbidity, mortality and use of health services among
      elderly depressed patients and general elderly populations.
AB  - OBJECTIVES: The aim of this study was to establish the predictive value of an ICD
      10 diagnosis of depressive disorder or dysthymia (depressive patients) among 70
      years + frail rural community living patients by measuring morbidity, mortality
      and use of health services. Identical measures were studied over time in general
      elderly populations. METHODS:  OUTCOME MEASURES: morbidity, mortality and use of
      health services were registered over 13 years in: (i) a clinical cohort of frail
      community-living depressive patients (n = 38), a frail control group (n = 116)
      and non-frail elderly people (n = 575), all living in the same municipality, and
      (ii) register-based samples of general rural (n = 4 115) and capital living (n =
      54 977) elderly populations. The outcome measures were compared using data from
      Danish national health registers. RESULTS: Every one of the clinical cohort of
      depressive patients had died at the end of the study. Compared with both the
      frail control group and the non-frail elderly people, the depressive patients had
      significantly more psychiatric hospital days, outpatient home visits,
      antidepressant use, antipsychotic use, GP service use and more psychiatric
      diagnoses with higher morbidity. However, greater use of somatic hospital
      services or more somatic diagnoses among the depressive elderly patients were not
      observed. The general elderly population living in the capital had, compared with
      rural equals, significantly more somatic and psychiatric diagnoses, larger use of
      somatic hospital services, psychiatric hospital days, antipsychotics and
      anxiolytics, but less use of antidepressants, psychiatric outpatient home visits
      and GP services. CONCLUSIONS: An ICD-10 diagnosis of depressive disorder or
      dysthymia predicted increased use of psychiatric services, more psychiatric
      diagnoses and increased mortality, indicating poor late-life psychiatric outcome.
      Contrasting with other studies, depression did not predict increased use of
      somatic hospital services or more somatic diagnoses. The differences in health
      care status and use between elderly living in the capital and in rural areas
      elderly are novel findings.

PMID- 21870924
TI  - Group cognitive behaviour therapy for military service-related post-traumatic
      stress disorder: effectiveness, sustainability and repeatability.
AB  - OBJECTIVE: The aim of this study was to assess 12 month outcomes of Australian
      combat veterans with post-traumatic stress disorder (PTSD) who participated in a
      6 week group-based CBT programme at the Toowong Private Hospital. The study
      population included 496 consecutive admissions to the programme between 1999 and
      2008. METHOD: Self-report measures of PTSD, depression, anxiety, anger, alcohol
      use, relationship satisfaction and quality of life parameters were collected at
      intake and 3, 6 and 12 months post intake. RESULTS: Statistically significant and
      sustained improvements were noted in 12 month outcome measures for PTSD,
      depression, anxiety, alcohol use, anger, and quality of life. PTSD symptom
      reduction occurred consistently each year for 9 years and exhibited an aggregated
      effect size of 0.68. CONCLUSIONS: This naturalistic research demonstrates that
      treatment administered under clinical conditions produces equivocal magnitudes of
      positive change in terms of PTSD symptoms when compared with existing efficacy
      data in individual and group treatments. Further, these symptomatic gains are
      sustainable and consistently reproducible. The benefits noted from group therapy
      were seen as independent of whether or not individual treatment was in place.

PMID- 21870925
TI  - Cost-effectiveness of an early assessment service for young people with early
      psychosis in Hong Kong.
AB  - OBJECTIVE: The Early Assessment Service for Young People with Early Psychosis
      (EASY) was developed in Hong Kong in 2001 to provide a comprehensive and
      integrated approach for early detection and intervention for young people
      suffering from first episode psychosis. The present study examined the cost
      effectiveness of the service over a period of 24 months compared to standard
      care. METHOD: This is a historical control study. Sixty-five patients who
      presented to the EASY service in 2001 with first episode psychosis were
      individually matched (on age, sex and diagnosis) with 65 patients who received
      standard psychiatric care in a precursor service (pre-EASY) between 1999 and
      2000. A retrospective cost-effectiveness analysis was conducted over a period of
      24 months. The overall average cost of service utilization per patient and the
      effects on hospitalization rate were compared using bootstrapping analysis. Cost
      per point improvement in Positive and Negative Syndrome Scale (PANSS) was also
      computed with sensitivity analysis. Only direct costs were analysed in the
      current study. RESULTS: There was no significant difference in service
      utilization between the EASY and pre-EASY standard care groups. The cost
      effectiveness acceptability curve, which was used to explore uncertainty in
      estimates of cost and effects, suggested that there was a probability of at least
      94% that the EASY model was more cost-effective than the pre-EASY service in
      reducing psychiatric inpatient admissions. EASY patients also showed superior
      results in average cost per unit improvement in PANSS. CONCLUSIONS: EASY is
      likely to be more cost-effective in improving outcomes, particularly in reducing
      hospitalization and improving clinical symptoms among young people with first
      episode psychosis. This study provides a perspective from the east Asian region,
      and supports further development of similar services, particularly in the local
      setting. However, further studies with a longer follow up period and larger
      sample size are required to verify these findings.

PMID- 21870926
TI  - Concurrent treatment of depression and auditory hallucinations in a patient with
      schizophrenia.

PMID- 21870927
TI  - Evaluation of reproductive toxicity in male rats treated with novel synthesized
      ruthenium(II) and gold(I)-NHC complexes.
AB  - In this study, we aimed to determine the reproductive toxicity in rat induced by
      ruthenium(II)-NHC (Ru(II)) and gold(I)-NHC (Au(I)) complexes that have
      anticarcinogenic effects. For this purpose, 35 Sprague-Dawley rats were randomly
      divided into 5 equal groups. In control group, rats treated with saline, Ru(II),
      and Au(I) complexes were intraperitoneally given high (10 mg/kg) and low (5
      mg/kg) doses to rats via a one-time administration. The animals were sacrificed,
      and testis tissues were taken on Day 10 of the drug administration for the
      determination of the biochemical, histopathological, spermatological, and
      hormonal parameters. It was determined that treatment group that was subjected to
      treatment using both Ru(II) and Au(I) complexes significantly caused oxidative,
      histopathological, spermatological, and hormonal damage compared to control
      group. However, the sexual and accessory organ weight did not significantly
      change when compared to control. In addition, it was shown that Au(I) treatment
      generally caused more adverse effects than Ru(II) treatment in a dose-dependent
      manner. In conclusion, when these synthesized compounds are used for the
      treatment of cancer, they could cause toxic effects on male reproductive system
      and lead to infertility. However, Ru(II) complex is a more preferable option in
      cancer treatment, particularly in terms of user safety.

PMID- 21870932
TI  - Experiences of social exclusion and bullying at school among children and youth
      with cerebral palsy.
AB  - PURPOSE: Although bullying amongst typically developing school-aged children has
      been well explored, it is under-researched for children with disabilities. The
      purpose of this study was to understand the experiences of exclusion and bullying
      among children with disabilities. METHOD: We draw on qualitative in-depth
      interviews and a focus group with children and youth with disabilities (n = 15)
      to explore their experiences of exclusion and bullying. RESULTS: Our results
      showed that restrictions in the socio-contextual environment influenced the
      social exclusion that children experienced. Youth encountered social exclusion
      from both teachers and peers. Children reported that teachers' attitudes toward
      children with disabilities often influenced the social exclusion experienced by
      peers. Bullies engaged in both implicit and explicit forms of social exclusion
      toward children with disabilities which often lead to verbal and physical
      bullying. CONCLUSIONS: Children with cerebral palsy are victims of bullying and
      social exclusion within the school context. More opportunities for social
      inclusion are needed.

PMID- 21870933
TI  - Evaluation of oil content and fatty acid composition of five endemic Bupleurum
      species growing in the Central Anatolia region of Turkey.
AB  - The fatty acid composition of five endemic Bupleurum (Apiaceae) species was
      analysed by GC technique for their nutritional value. The amount of oil content
      of the species varied from 3.77% to 7.03%. Twenty-one fatty acids were identified
      in the oils. The fatty acid composition of the studied species contained oleic,
      palmitic and linoleic acids as the major components. Oleic acid ranged from 8.81%
      to 68.30%, while the levels of palmitic acid were found to be between 12.47% and
      47.85%. Bupleurum lycaonicum, Bupleurum sulphureum and Bupleurum heldreichii are
      very good sources of oleic acid. The remaining species were characterised as
      containing the highest level of palmitic acid. In this study, the total saturated
      fatty acids ranged between 15.02 and 65.20%, while total monounsaturated fatty
      acids were between 18.10 and 70.65%. The total polyunsaturated fatty acid
      accounted for 13.47-35.20% of the studied fatty acids. Therefore, we can conclude
      that Bupleurum oils have a significant nutritional value.

PMID- 21870934
TI  - Two new compounds from the roots of Ilex pubescens.
AB  - A new triterpenoid glycoside, heterobetulinic acid 3-O-beta-D-glucopyranosyl(1 ->
      2)-beta-D-xylopyranoside (1), together with a new phenylacrylic acid derivative,
      3'S,4'-dihydroxyl-2'-methylene-but-1'-enyl caffeate (2), were isolated from the
      roots of Ilex pubescens. Their structures were elucidated by HR-ESI-MS, 1-D and 2
      D NMR analyses and chemical methods. In addition, the absolute configuration of 2
      was established by the application of a modified Mosher's method.

PMID- 21870935
TI  - Life satisfaction in people with spinal cord injury during the first five years
      after discharge from inpatient rehabilitation.
AB  - PURPOSE: To describe the course of life satisfaction in persons with spinal cord
      injury (SCI) during the first 5 years after discharge from inpatient
      rehabilitation and to examine its determinants. METHODS: Multi-centre prospective
      cohort study with four measurements, the first at discharge from inpatient
      rehabilitation, the last 5 years after discharge. Data of 162 persons with SCI
      were analyzed. Life satisfaction was measured as the sum score of 'current life
      satisfaction' and 'current life satisfaction compared to life satisfaction before
      SCI'. Lesion characteristics, functional independence, secondary impairments,
      pain, social support and self-efficacy were analyzed as possible determinants of
      life satisfaction. Random coefficient analysis was used for the analyses.
      RESULTS: No significant changes in life satisfaction were found between discharge
      and 2 years later, however there were significant increases from two to 5 years
      post discharge. High functional independence, low pain, high everyday social
      support and high self-efficacy were significant determinants of a positive course
      of life satisfaction after discharge. CONCLUSIONS: Increases in life satisfaction
      were found in persons with SCI in the long run. High functional status, low pain,
      good social skills and high self-efficacy were related to high life satisfaction.

PMID- 21870936
TI  - Phytochemical investigation characterisation and anticonvulsant activity of
      Ricinus communis seeds in mice.
AB  - The ethanol extract of the dried, powdered hull portion of Ricinus communis seeds
      indicated the presence of alkaloids, steroids, flavonoids, glycosides and
      phenolics, amongst others. Ricinine was isolated as an active constituent and
      characterised by various chemical and spectroscopic techniques. The
      anticonvulsant activity of the isolated compound was evaluated in mice using the
      maximal electroshock (MES) model. The isolated compound at a dose of 60 mg kg-1
      body weight, orally, significantly (p < 0.05) reduced the extensor tonus phase of
      convulsion by MES-induced seizures in albino mice when compared with the standard
      drug diazepam (30 mg kg-1 body weight, orally). The results of this study support
      the folkloric use of the plant in epileptic remedies.

PMID- 21870938
TI  - Antioxidant and anti-inflammatory effects of Scoparia dulcis L.
AB  - Different extracts were obtained from Scoparia dulcis L. (Scrophulariaceae) by
      successive extraction with hexane, chloroform, and methanol. These extracts
      exhibited significant antioxidant capacity in various antioxidant models mediated
      (xantine oxidase and lipoxygenase) or not mediated (2,2-diphenyl-picrylhydrazyl,
      ferric-reducing antioxidant power, beta-carotene bleaching, lipid peroxidation)
      by enzymes. The antioxidant activity of the extracts was related to their
      phytochemical composition in terms of polyphenol and carotenoid contents. The
      chloroform extract was richest in phytochemicals and had the highest antioxidant
      activity in the different antioxidant systems. All the extracts exhibited less
      than 50% inhibition on xanthine oxidase but more than 50% inhibition on lipid
      peroxidation and lipoxygenase. The extracts strongly inhibited lipid peroxidation
      mediated by lipoxygenase.

PMID- 21870939
TI  - Ethnobotanical survey, chemical composition, and antioxidant capacity of
      methanolic extract of the root bark of Annona cuneata Oliv.
AB  - The root bark of Annona cuneata Oliv. is traditionally used in the Democratic
      Republic of Congo to treat several debilitating conditions, such as hernia,
      female sterility, sexual asthenia, and parasitic infections. However, little is
      known about the composition of the secondary plant substances, which may
      contribute to these traditional medicinal effects. We conducted an ethnobotanical
      study and then evaluated the composition of the secondary plant substances in
      extracts of the root bark by using spectroscopic methods. After delipidation, the
      root bark was lixiviated in methanol, and components in the extract were studied
      by gas chromatography-mass spectometry, high-performance liquid chromatography
      (HPLC)-electrospray ionization-MS and nano-electrospray ionization-MS-MS. These
      methods identified 13 secondary plant substances (almost exclusively phenolic
      compounds): p-hydroxybenzaldehyde (I), vanillin (II), tyrosol (III), 3,4
      dihydroxybenzaldehyde (IV), p-hydroxybenzoic acid (V), vanillyl alcohol (VI),
      syringaldehyde (VII), 4-hydroxy-3-methoxyphenylethanol (VIII), vanillic acid
      (IX), 3,4-dihydroxybenzoic acid (X), syringic acid (XI), and ferulic acid (XII),
      along with the phytosterol squalene (XIII). In the HPLC-based
      hypoxanthine/xanthine oxidase antioxidant assay system, the methanolic extract
      exhibited potent antioxidant capacity, with a 50% inhibitory concentration of 72
      MUL, equivalent to 1.38 mg/mL of raw extract. Thus, a methanol extract of A.
      cuneata Oliv. contained a range of polyphenolic compounds, which may be partly
      responsible for its known traditional medicinal effects. More detailed studies on
      the phytochemistry of this important plant species are therefore warranted.

PMID- 21870940
TI  - X-ray diffraction enhanced imaging as a novel method to visualize low-density
      scaffolds in soft tissue engineering.
AB  - Scaffold visualization is challenging yet essential to the success of various
      tissue engineering applications. The aim of this study was to explore the
      potential of X-ray diffraction enhanced imaging (DEI) as a novel method for the
      visualization of low density engineered scaffolds in soft tissue. Imaging of the
      scaffolds made from poly(L-lactide) (PLLA) and chitosan was conducted using
      synchrotron radiation-based radiography, in-line phase-contrast imaging (in-line
      PCI), and DEI techniques as well as laboratory-based radiography. Scaffolds were
      visualized in air, water, and rat muscle tissue. Compared with the images from X
      ray radiography and in-line PCI techniques, DEI images more clearly show the
      structure of the low density scaffold in air and have enhanced image contrast.
      DEI was the only technique able to visualize scaffolds embedded in unstained
      muscle tissue; this method could also define the microstructure of muscle tissue
      in the boundary areas. At a photon energy of 20 KeV, DEI had the capacity to
      image PLLA/chitosan scaffolds in soft tissue with a sample thickness of up to 4
      cm. The DEI technique can be applied at high X-ray energies, thus facilitating
      lower in vivo radiation doses to tissues during imaging as compared to
      conventional radiography.

PMID- 21870941
TI  - Optimization of the isolation, culture, and characterization of equine umbilical
      cord blood mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSC) represent a promising population for supporting
      new clinical concepts in cellular therapy. A wide diversity of isolation
      procedures for MSC from umbilical cord blood (UCB) has been described for humans.
      In contrast, a few data are available in horses. In the current study, a
      sedimentation method using hydroxyethyl starch and a method based on the lysis of
      red blood cells using ammonium chloride (NH(4)Cl) were compared with two density
      gradient separation methods (Ficoll-Paque and Percoll). Adherent cell colonies
      could be established using all four isolation methods. The mononuclear cell
      recovery after Percoll separation, however, resulted in significantly more
      putative MSC colonies; and, therefore, this isolation method was used for all
      further experiments. Culture conditions such as cell density and medium or serum
      coating of the wells did not significantly affect putative MSC recovery. Isolated
      MSC using Percoll were subsequently differentiated toward the osteogenic,
      chondrogenic, and adipogenic lineage. In addition, MSC were phenotyped by
      multicolor flow cytometry based on their expression of different cell protein
      markers. Cultured MSC were CD29, CD44, and CD90-positive and CD79alpha,
      Macrophage/Monocyte and MHC II-negative. In conclusion, this study reports
      optimized protocols to isolate, culture, and characterize solid equine MSC from
      UCB.

PMID- 21870942
TI  - Osteogenic differentiation and ectopic bone formation of canine bone marrow
      derived mesenchymal stem cells in injectable thermo-responsive polymer hydrogel.
AB  - This study describes an injectable, thermo-responsive hyaluronic acid-g-chitosan
      g-poly(N-isopropylacrylamide) (HA-CPN) copolymer for bone tissue engineering. The
      wettability, temperature-dependent change of water content, and volume of HA-CPN
      hydrogel were measured, together with its biocompatibility in vitro and in vivo.
      The dried hydrogel morphology shows a three-dimensional, porous structure with
      interconnected pores. Canine bone marrow-derived mesenchymal stem cells (cBMSCs)
      were encapsulated in HA-CPN hydrogel and osteoinduction was assessed by comparing
      samples with different osteogenic differentiation induction times but with the
      same total cell culture time. Cell proliferation and time-dependent osteogenic
      differentiation, evident from secretion of extracellular matrix and formation of
      mineral deposits, were observed. The cells showed better proliferation in HA-CPN
      hydrogel than on tissue culture polystyrene after osteo-induced for 21 days and
      higher alkaline phosphatase activity regardless of osteo-induction times.
      Mineralization extent of cBMSCs in HA-CPN followed by Alizarin red stains showed
      positive stained nodules after osteo-induced longer than 7 days. The
      cells/hydrogel construct also showed increased mechanical strength and elasticity
      after osteogenic differentiation, and the increase could be correlated with osteo
      induction time. In vivo studies confirmed the biocompatibility and bioresorption
      of the HA-CPN hydrogel and ectopic bone formation when the hydrogel was used as a
      cell carrier for osteo-induced cBMSCs and implanted in nude mice subcutaneously.
      Taken together, the results indicate the feasibility and efficacy of HA-CPN
      hydrogel as an injectable bone tissue engineering scaffold with cBMSCs.

PMID- 21870943
TI  - Antibody-mediated osseous regeneration: a novel strategy for bioengineering bone
      by immobilized anti-bone morphogenetic protein-2 antibodies.
AB  - Bone regeneration often requires harvesting of autologous bone with significant
      potential morbidity and cost. Recombinant human bone morphogenetic protein
      (rhBMP)-2 has been approved by the U.S. Food and Drug Administration for specific
      regenerative indications. However, administration of exogenous growth factors has
      many drawbacks. The objective of the present proof-of-concept study was to
      determine whether immobilized anti-BMP-2 antibodies (Abs) could capture
      endogenous BMP-2 in local sites to mediate osteogenesis, a strategy we refer to
      as antibody-mediated osseous regeneration (AMOR). We have generated a murine anti
      BMP-2 monoclonal antibody library, which was tested along with commercially
      available Abs in vitro and in vivo for their ability to mediate AMOR. In vitro
      studies demonstrated that only some anti-BMP-2 Abs tested formed immune complexes
      with BMP-2, which can bind to BMP cellular receptor, whereas other BMP-2/anti-BMP
      2 complexes failed to bind. To investigate whether anti-BMP-2 Abs were able to
      mediate AMOR in vivo, anti-BMP-2 Abs were immobilized on absorbable collagen
      sponge (ACS) and surgically placed in rat calvarial defects. Microcomputed
      tomography analysis of live animals at 2, 4, and 6 weeks demonstrated that some
      anti-BMP-2 Abs immobilized on ACS mediated significant bone regeneration, whereas
      other clones did not mediate any bone regeneration. In situ BMP-2 and osteocalcin
      expression was investigated by immunohistochemistry. Results demonstrated higher
      BMP-2 and osteocalcin expression in sites with increased bone regeneration.
      Results provide first evidence for the ability of anti-BMP2 Abs to form an immune
      complex with endogenous BMP-2 and mediate bone regeneration in vivo, suggesting a
      promising therapeutic method for tissue engineering.

PMID- 21870944
TI  - Medical events during the 2009 Los Angeles County Station Fire: lessons for
      wildfire EMS planning.
AB  - BACKGROUND: Little is known about the types of injuries and medical problems
      encountered by fire department personnel during suppression of large campaign
      type wildland fires. Such information could help to plan for response to medical
      incidents during future wildfires. OBJECTIVE: To describe the injuries and
      medical problems experienced by firefighters during the 2009 Los Angeles County
      Station Fire. METHODS: This was a retrospective analysis of case records of
      patients treated during the Los Angeles County Station Fire. Data were abstracted
      from two sources: the incident command medical tracking sheet and prehospital
      patient care reports (PCRs). RESULTS: The sample included 183 patient contacts,
      of which PCRs were available for 65. For the remaining 118 patients, data were
      abstracted from the incident command medical tracking sheet. The most common
      chief complaint was extremity injury, accounting for 44 patient contacts (24% of
      all patients), with smoke inhalation second, at 32 patient contacts (17%). Of the
      65 patients with PCRs, 31 (52%) were treated with oxygen, 26 (40%) had
      intravenous (IV) lines started, and 15 (23%) received an IV fluid bolus. Half of
      the patients were transported to an emergency department (ED); the remainder were
      treated on scene or self-transported to a non-acute care facility. CONCLUSIONS:
      Most firefighter injuries and illnesses encountered during the Los Angeles
      Station Fire were minor. The prevalence of injuries observed should be taken into
      consideration in creation of protocols and mandatory equipment lists for fireline
      paramedics. Furthermore, advanced training for paramedics in the diagnosis and
      treatment of minor medical conditions may be useful.

PMID- 21870945
TI  - Comparison of two packable hemostatic Gauze dressings in a porcine hemorrhage
      model.
AB  - BACKGROUND: Uncontrolled hemorrhage remains the primary cause of preventable
      battlefield mortality and a significant cause of domestic civilian mortality.
      Rapid hemorrhage control is crucial for survival. ChitoGauze and Combat Gauze are
      commercially available products marketed for rapid hemorrhage control. These
      products were selected because they are packable gauze that work via differing
      mechanisms of action (tissue adhesion versus procoagulant). OBJECTIVE: To compare
      the effectiveness of ChitoGauze and Combat Gauze in controlling arterial
      hemorrhage in a swine model. METHODS: Fourteen swine were studied. Following
      inguinal dissection and after achieving minimum hemodynamic parameters (mean
      arterial pressure [MAP] >= 70 mmHg), a femoral arterial injury was created using
      a 6-mm vascular punch. Free bleeding was allowed for 45 seconds, and then the
      wound was packed alternatively with ChitoGauze or Combat Gauze. Direct pressure
      was applied to the wound for 2 minutes, followed by a three-hour monitoring
      period. Resuscitation fluids were administered to maintain an MAP of >= 65 mmHg.
      Time to hemostasis, hemodynamic parameters, total blood loss, and amount of
      resuscitation fluid were recorded every 15 minutes. Data were analyzed using the
      Wilcoxon rank sum test. Histologic sections of the vessels were examined using
      regular and polarized light. RESULTS: No statistically significant differences
      were found between the groups regarding any measured end point. Data trends,
      however, favor ChitoGauze over Combat Gauze for time to hemostasis, fluid
      requirements, and blood loss. There was no evidence of retained foreign material
      on histologic analysis. CONCLUSION: ChitoGauze and Combat Gauze appear to be
      equally efficacious in their hemostatic properties, as demonstrated in a porcine
      hemorrhage model.

PMID- 21870946
TI  - Does mechanism of injury predict trauma center need?
AB  - OBJECTIVE: To determine the predictive value of the mechanism-of-injury step of
      the American College of Surgeons Field Triage Decision Scheme for determining
      trauma center need. METHODS: Emergency medical services (EMS) providers caring
      for injured adult patients transported to the regional trauma center in three
      midsized communities over two years were interviewed upon emergency department
      (ED) arrival. Included was any injured patient, regardless of injury severity.
      The interview collected patient physiologic condition, apparent anatomic injury,
      and mechanism of injury. Using the 1999 Scheme, patients who met the physiologic
      or anatomic steps were excluded. Patients were considered to need a trauma center
      if they had nonorthopedic surgery within 24 hours, had intensive care unit
      admission, or died prior to hospital discharge. Data were analyzed by calculating
      positive likelihood ratios (+LRs) and 95% confidence intervals (CIs) for each
      mechanism-of-injury criterion. RESULTS: A total of 11,892 provider interviews
      were conducted. Of those, one was excluded because outcome data were not
      available, and 2,408 were excluded because they met the other steps of the Field
      Triage Decision Scheme. Of the remaining 9,483 cases, 2,363 met one of the
      mechanism-of-injury criteria, 204 (9%) of whom needed the resources of a trauma
      center. Criteria with a +LR >= 5 were death of another occupant in the same
      vehicle (6.8; CI: 2.7-16.7), fall >20 feet (5.3; CI: 2.4-11.4), and motor vehicle
      crash (MVC) extrication time >20 minutes (5.1; CI: 3.2-8.1). Criteria with a +LR
      between >2 and <5 were intrusion >12 inches (4.2; CI: 2.9-5.9), ejection (3.2;
      CI: 1.3-8.2), and deformity >20 inches (2.5; CI: 1.9-3.2). The criteria with a
      +LR <= 2 were MVC speed >40 mph (2.0; CI: 1.7-2.4), pedestrian/bicyclist struck
      at a speed >5 mph (1.2; CI:1.1-1.4), bicyclist/pedestrian thrown or run over
      (1.2; CI: 0.9-1.6), motorcycle crash at a speed >20 mph (1.2; CI: 1.1-1.4), rider
      separated from motorcycle (1.0; CI: 0.9-1.2), and MVC rollover (1.0; CI: 0.7
      1.5). CONCLUSION: Death of another occupant, fall distance, and extrication time
      were good predictors of trauma center need when a patient did not meet the
      anatomic or physiologic conditions. Intrusion, ejection, and vehicle deformity
      were moderate predictors. Key words: wounds and injury; triage; emergency medical
      services; emergency medical technicians; predictors; mechanism of injury; trauma
      center.

PMID- 21870947
TI  - Ambulance diversion and emergency department offload delay: resource document for
      the National Association of EMS Physicians position statement.
AB  - The emergency medical services (EMS) system is a component of a larger health
      care safety net and a key component of an integrated emergency health care
      system. EMS systems, and their patients, are significantly impacted by emergency
      department (ED) crowding. While protocols designed to limit ambulance diversion
      may be effective at limiting time on divert status, without correcting overall
      hospital throughput these protocols may have a negative effect on ED crowding and
      the EMS system. Ambulance offload delay, the time it takes to transfer a patient
      to an ED stretcher and for the ED staff to assume the responsibility of the care
      of the patient, may have more impact on ambulance turnaround time than ambulance
      diversion. EMS administrators and medical directors should work with hospital
      administrators, ED staff, and ED administrators to improve the overall efficiency
      of the system, focusing on the time it takes to get ambulances back into service,
      and therefore must monitor and address both ambulance diversions and ambulance
      offload delay. This paper is the resource document for the National Association
      of EMS Physicians position statement on ambulance diversion and ED offload time.
      Key words: ambulance; EMS; diversion; bypass; offload; delay.

PMID- 21870948
TI  - Cardiopulmonary resuscitation or shock first--no answers yet?

PMID- 21870950
TI  - Temporal and spatial changes in cartilage-matrix-specific gene expression in
      mesenchymal stem cells in response to dynamic compression.
AB  - Various forms of mechanical stimulation have been shown to enhance chondrogenesis
      of mesenchymal stem cells (MSCs). However, the response of MSCs undergoing
      chondrogenesis to such signals has been shown to depend on the temporal
      application of loading. The objective of this study was to determine the effect
      of dynamic compression on cartilage-matrix-specific gene expression and to relate
      this response to the local biochemical environment and cell phenotype at the time
      of loading. At 0, 7, 14, and 21 days extracellular matrix (ECM) deposition within
      MSC-seeded agarose hydrogels due to transforming growth factor-beta3 stimulation
      was determined biochemically and histologically, and then reverse transcription
      polymerase chain reaction was used to examine the effects of dynamic compression
      on cartilage-matrix-specific gene expression. The results of these experiments
      show that the local environment in the core of the constructs is more favorable
      for chondrogenesis in comparison to the annulus, as evident from both ECM
      synthesis and gene expression. Additionally, we found that the response of the
      cells to mechanical stimulus varied with both the spatial region within the
      constructs and the temporal application of loading. Dynamic compression applied
      at day 21 was found to enhance levels of cartilage matrix gene expression
      following a peak in expression levels at day 14 in free swelling constructs,
      suggesting that mechanical signals play a key role in the maintenance of a
      chondrogenic phenotype. The application of mechanical stimulus to enhance
      cartilage ECM synthesis may be an important tool in regenerative medicine-based
      cartilage repair. The results of this study suggest that a chondrogenic phenotype
      and/or a well-developed pericellular matrix must first be established before
      dynamic compression can have a positive effect on cartilage-matrix-specific gene
      expression.

PMID- 21870951
TI  - Parental disciplinary practices following acquired brain injury in children.
AB  - PURPOSE: This study describes the disciplinary practices of parents following
      acquired brain injury (ABI) of their child and examines the relationship between
      disciplinary use, family-parental adversities and children's behavioural
      sequelae. METHOD: Participants were 48 parent respondents of children between 3
      12 years with mild, moderate and severe ABI. Parents provided demographic
      information and completed questionnaires investigating disciplinary strategy use,
      parental-family functioning and child behaviour. RESULTS: Over-reactive and lax
      disciplinary strategies were endorsed most by parents. Dysfunctional levels of
      disciplinary use were associated with children who displayed more behaviour
      problems, parents with elevated distress and families experiencing more
      dysfunction and social adversity. CONCLUSION: Dysfunctional parenting practices,
      if not ameliorated, could exacerbate problematic child behaviour following ABI,
      as well as parent and family difficulties. Parental assessment may be useful as a
      method of screening for parental factors that put children at risk for ongoing
      behaviour problems and families for ongoing stress.

PMID- 21870952
TI  - Enabling two women with blindness and additional disabilities to make phone calls
      independently via a computer-aided telephone system.
AB  - OBJECTIVE: To assess whether two women with blindness and additional disabilities
      could make independent phone calls through a computer-aided telephone system.
      METHOD: For each participant, the study involved an ABAB design, in which the A
      represented baseline phases and the B represented intervention phases with the
      special telephone system (involving among others a net-book computer with
      specific software, a global system for mobile communication modem and a
      microswitch). RESULTS: Both participants learned to use the system and made phone
      calls independently to a variety of partners such as family members, friends and
      staff personnel. CONCLUSION: The system assessed in this study might represent a
      useful means for enabling persons with blindness and additional disabilities to
      manage phone calls on their own.

PMID- 21870953
TI  - Autism spectrum disorders and motor skills: the effect on socialization as
      measured by the Baby And Infant Screen For Children with aUtIsm Traits (BISCUIT).
AB  - PURPOSE: To examine the effects of ASD diagnosis and motor skills on
      socialization in young children. METHODS: Two samples were used: gross motor
      skills sample (n = 408) and fine motor skills sample (n = 402). The Battelle
      Developmental Inventory-Second Edition assessed motor skills, while the Baby and
      Infant Screen for Children with aUtIsm Traits, Part 1 assessed socialization.
      RESULTS: A main effect of diagnosis was found for both samples on socialization
      such that those with autism exhibited the most severe deficits followed by those
      with PDD-NOS and then atypically developing children. There was a main effect for
      gross motor skills, with high gross motor skills showing less social impairment.
      The interaction term was only significant in regards to fine motor skills.
      CONCLUSIONS: The individual effects of ASD diagnosis and motor impairment as well
      as the interaction have implications for the assessment and treatment in these
      individuals.

PMID- 21870954
TI  - An outpatient group training programme for improving leisure lifestyle in high
      functioning young adults with ASD: a pilot study.
AB  - OBJECTIVE: This study examined the effectiveness of an outpatient programme on
      the leisure lifestyle of high-functioning young adults living at home or at an
      independent setting. METHODS: A pre-test-post-test control group design was used.
      Participants (n = 12) completed self-reports on (a) need for leisure support, (b)
      leisure engagement and (c) satisfaction with leisure lifestyle. The programme
      consisted of cognitive-behavioural techniques. RESULTS: Significant within-group
      changes for the experimental group (n = 7) were found, indicating decreases in
      'need for leisure support', more regular leisure engagement patterns and an
      increase in 'leisure satisfaction' following the programme. Between-group
      statistics reveal medium and large effect sizes for decreases in need for leisure
      support and a medium effect size for increase in 'leisure satisfaction', all in
      favour of the experimental group. Results regarding 'leisure engagement' were
      less clear. CONCLUSION: The preliminary programme was effective in improving
      leisure lifestyle and suggestions for future research are discussed.

PMID- 21870955
TI  - The use of the Battelle Developmental Inventory-Second Edition (BDI-2) as an
      early screener for autism spectrum disorders.
AB  - PURPOSE: The purpose was to develop cut-off scores for a measure of developmental
      level (Battelle Developmental Inventory-Second Edition; BDI-2) which could be
      used as a screening tool to differentiate young children with possible autism
      spectrum disorders (ASD). METHODS: Infants and toddlers with ASD (n = 604) and
      atypically-developing infants and toddlers (n = 1064) were administered the BDI
      2. Cut-off scores were determined based on standard deviations from the mean of
      the ASD group. RESULTS: Using 1.5 standard deviations from the mean of the ASD
      group, a cut-off score of 96 was determined which had a sensitivity of 0.94 and a
      specificity of 0.31. CONCLUSIONS: With high sensitivity, these cut-off scores can
      be used to identify children who require further assessment. In addition, the
      measure can be used to determine treatment targets.

PMID- 21870956
TI  - Cognitive and speech-language performance in children with ataxia telangiectasia.
AB  - OBJECTIVE: To describe cognitive and speech-language functioning of patients with
      ataxia-telangiectasia (A-T) in relation to their deteriorating (oculo)motor
      function. DESIGN: Observational case series. METHODS: Cognitive functioning,
      language, speech and oral-motor functioning were examined in eight individuals
      with A-T (six boys, two girls), taking into account the confounding effects of
      motor functioning on test performance. RESULTS: All patients, except the youngest
      one, suffered from mild-to-moderate/severe intellectual impairment. Compared to
      developmental age, patients showed cognitive deficits in attention, (non)verbal
      memory and verbal fluency. Furthermore, dysarthria and weak oral-motor
      performance was found. Language was one of the patients' assets. CONCLUSION: In
      contrast to the severe deterioration of motor functioning in A-T, cognitive and
      language functioning appeared to level off with a typical profile of
      neuropsychological strengths and weaknesses. Based on our experiences with A-T,
      suggestions are made to determine a valid assessment of the cognitive and speech
      language manifestations.

PMID- 21870957
TI  - Hemihydranencephaly syndrome: case report and review.
AB  - BACKGROUND: Hemihydranencephaly (HHDNC) is a rare disorder with complete or
      almost complete unilateral absence of cerebral cortex. METHODS: This study
      describes a 27 months-old girl presenting with developmental delay and
      generalized weakness more on the left side. Bilateral blindness was noted since
      the age of 6 months. RESULTS: Her fundus examination revealed bilateral optic
      atrophy, dilated tortuous retinal veins with increased intra-ocular tension. She
      had polyuria and recurrent attacks of dehydration due to neurogenic diabetes
      insipidus. Her blood protein S was deficient. Her magnetic resonance imaging
      (MRI) demonstrated HHDNC with nearly complete absence of the right cerebral
      hemisphere. Her MR-Arteriography demonstrated total occlusion of right middle and
      anterior cerebral arteries and attenuated and beaded right posterior cerebral
      artery. Diffusion tensor MR imaging revealed complete absence of right cortico
      spinal and optic tracts with deficient left sided tracts. CONCLUSION: In contrast
      to the good outcome of the few reported cases of HHDNC, this case had severe
      global disabilities.

PMID- 21870958
TI  - Disease specific advance care planning for heart failure patients: implementation
      in a large health system.
AB  - PURPOSE: This study evaluates the implementation of Disease Specific Advance Care
      Planning (DS-ACP) for heart failure patients in a large health care system. The
      DS-ACP model uses a trained facilitator to guide communication between patient
      and proxy regarding patient values and goals for treatment in worst-case
      scenarios, develop a disease specific documentation plan, and identify needed
      resources. METHODS: Referral and DS-ACP service delivery data were merged with
      electronic health record data. Process measures for implementation are described.
      Patients who participated in DS-ACP are compared with those who did not on
      demographics, medical characteristics, and outcomes such as inpatient
      readmissions, and hospice use among those who died. A chart audit was completed
      on a sample of patients to examine differences in advance care planning
      documentation between participants and nonparticipants. RESULTS: Nearly one third
      (31.8%) of the 1894 heart failure patients referred to DS-ACP participated.
      Referral method was associated with participation. A chart audit revealed 94.3%
      of those completing the DS-ACP process, had a health directive compared to 24.8%
      of noncompleters (p<0.001). Of the patients who died by the end of the study
      period (n=286), DS-ACP participants were more likely to have used hospice
      compared to nonparticipants (56% versus 37%, p=0.002). CONCLUSIONS: These initial
      evaluation results indicate the DS-ACP model, previously tested in randomized
      trials, can be successfully implemented among heart failure patients in a large
      health care system. Results demonstrate the importance of referral method and
      show initial positive results for participation, improved documentation, and
      hospice use.

PMID- 21870959
TI  - In vitro validation of a Respimat(r) adapter for delivery of inhaled
      bronchodilators during mechanical ventilation.
AB  - BACKGROUND: Inhaled bronchodilators are frequently used in patients with chronic
      obstructive pulmonary disease (COPD). However, there has been no efficient way to
      administer the long-acting anticholinergic tiotropium to mechanically ventilated
      patients. The aim of this in vitro study was to compare the fine particle dose
      (FPD) output of a specifically designed adapter with other accessory devices for
      the delivery of bronchodilators using the Respimat(r) (RMT) inhaler by simulating
      the specific inhalation flow profiles of patients with COPD. METHODS: Using
      characteristic flow profiles from COPD patients being weaned off mechanical
      ventilation, an in vitro study was performed analyzing the FPD achieved with
      different accessory devices (connectors, spacers, AeroTrachPlus valved holding
      chamber), which can be used to deliver drugs from pressurized metered dose
      inhalers (pMDI) and RMT inhalers to artificial airways. Fenoterol pMDI,
      tiotropium RMT, and a fixed-dose combination of salbutamol and ipratropium
      delivered by pMDI or RMT, were used as bronchodilators. Aerosols were collected
      by a next-generation impactor. RESULTS: The RMT inhaler, combined with a new in
      line adapter, was superior to other inhaler device connector or spacer
      combinations in FPD delivery during simulated mechanical ventilation (p<0.01).
      The outcome with the RMT inhaler/RMT adapter combination during simulation of
      mechanical ventilation was comparable to the measurements with the
      RMT/AeroTrachPlus valved holding chamber during simulation of spontaneous
      breathing. The delivery rates of the RMT adapter were not significantly affected
      by the administered bronchodilators or by the type of artificial airway
      (endotracheal or tracheostomy tube) employed. CONCLUSIONS: The RMT inhaler
      combined with the prototype in-line adapter was better than the other accessory
      device combinations in fine particle deposition of inhaled bronchodilators during
      mechanical ventilation. Further research is required to determine the clinical
      relevance of these in vitro findings.

PMID- 21870960
TI  - A new method of chronic and recurrent seminal vesiculitis treatment.
AB  - PURPOSE: To investigate a new method and its effect on the procedure of dilating
      the ejaculatory duct and flushing the seminal vesicle with an F9 seminal vesicle
      scope in patients with chronic and recurrent seminal vesiculitis. PATIENTS AND
      METHODS: Twenty-six patients with a diagnosis based to signs, laboratory
      detection, digital rectal examination, and transrectal ultrasonography were
      involved in present study. The patients underwent a surgical procedure of
      dilating the ejaculatory duct and flushing the seminal vesicles with an F9
      seminal vesicle endoscope. All patients were followed for 3 months to 1 year
      after treatment. RESULTS: There were significant reductions in symptoms, signs,
      white blood cell and red blood cell counts on microscopic examination, seminal
      vesicles size, improvement of inner walls echo in transrectal ultrasonography,
      and semen culture positive rate. Moreover, all patients showed improvement.
      CONCLUSIONS: The present study provides a new transurethral seminal tract
      endoscopic technique with seminal vesicle scope through the normal anatomic tract
      to treat patients with chronic seminal vesiculitis. It proved to be easily
      conducted with minimized complications. Further investigations are needed to
      confirm our results.

PMID- 21870961
TI  - A mitogenome of the Chevrier's field mouse (Apodemus chevrieri) and genetic
      variations inferred from the cytochrome b gene.
AB  - The Chevrier's field mouse (Apodemus chevrieri) is an endemic species to China
      and is an important pest in agriculture and human diseases. In this study, the
      complete mitochondrial genome of this species was sequenced and its size was
      16,298 bases (accession no.: HQ896683). The mitogenome structure was similar
      compared with other reported rodent mitochondrial genomes and includes 13 protein
      coding genes, 2 rRNA genes (12S rRNA and 16S rRNA), 22 tRNA genes, and 1 control
      region. This was the first complete mitogenome sequenced in genus Apodemus. The
      phylogenetic analyses based on the sequences of 12 heavy-strand protein-coding
      genes demonstrated that A. chevrieri clustered together with genus Mus.
      Additionally, extremely high haplotype and nucleotide diversities (h=0.978,
      pi=2.6%) were observed based on 44 mitochondrial cytochrome b (cyt b) gene
      sequences. This suggests adaptive divergence of this species to a variety of
      living habitats and potential refuges in the eastern margin of the Hengduan
      Mountains during the Quaternary ice ages. No population expansions or genetic
      bottlenecks were observed in demographic analyses. The phylogenetic analysis of
      cyt b sequences and haplotypes revealed a genetic differentiation between north
      and south populations. The divergence between north clade and south clade
      occurred probably in the middle Pleistocene 1.1815 million years ago (Mya) (95%
      highest posterior density 2.3189-0.2737 Mya), which was congruent with the
      periods of the most tense uplift events in the Tibetan Plateau.

PMID- 21870962
TI  - CD86 +1057G/A polymorphism and susceptibility to Ewing's sarcoma: a case-control
      study.
AB  - The development of Ewing's sarcoma (ES) is a complex process resulting from
      interplay between mutations in oncogenes and tumor suppressors, host
      susceptibility factors, and cellular context. CD86 (B7-2) may affect cancer
      susceptibility by modulating T cell response. CD86 +1057G/A polymorphism
      (rs1129055) has been reported to be associated with various diseases. Here, we
      investigated the association between CD86 +1057G/A polymorphism and the risk of
      ES in a Chinese population. The CD86 +1057G/A polymorphism was detected by
      polymerase chain reaction-restriction fragment length polymorphism in 158 ES
      cases and 212 age-matched healthy controls. Frequencies of CD86 +1057 AA genotype
      and +1057 A allele were significantly increased in patients with ES compared to
      healthy controls (odds ratio [OR]=2.12, 95% confidence interval [CI], 1.11-3.79,
      p=0.021; and OR=1.41, 95% CI, 1.10-1.91, p=0.018). Our data suggest that the
      +1057G/A polymorphism of the CD86 gene is associated with increased
      susceptibility to ES.

PMID- 21870963
TI  - Spousal violence against pregnant women from a Bedouin community in Jordan.
AB  - BACKGROUND: The objective of this study was to estimate the prevalence of spousal
      violence against pregnant women during their current pregnancy and investigate
      factors related to violence. METHODS: A cross-sectional survey was performed with
      303 pregnant women who attended antenatal clinics in Al-Mafraq, northern desert
      of Jordan. RESULTS: The prevalence of violence (any type) during pregnancy was
      40.9%. Physical violence was the highest (34.7 %), followed by psychologic
      violence (28.1%) and sexual violence (15.5%). Women who resided in the city (odds
      ratio [OR] 1.77, 95% confidence interval [CI] 1.05-2.79), had six or more
      pregnancies including the current one (OR 5.4, 95% CI 1.45-20.0), had four or
      more female children (OR 4.03, 95% CI 1.3- 11.9) and were under pressure to have
      a male child (OR 1.82, 95% CI 1.07- 3.08) were more likely to be exposed to
      violence during pregnancy. CONCLUSIONS: This study attempted to shed light on
      some of the cultural dimensions behind spousal violence, especially preference
      for male children. This study is important to the Jordanian and Arab communities
      in their efforts to protect women's rights and in designing interventions against
      domestic and spousal violence.

PMID- 21870964
TI  - Age determination of the glassy-winged sharpshooter, Homalodisca vitripennis,
      using wing pigmentation.
AB  - A red pigment is contained in the wing veins of the glassy-winged sharpshooter,
      Homalodisca vitripennis (Hemiptera: Cicadellidae). This insect is the main vector
      of the plant-pathogenic bacterium Xylella fastidiosa Wells (Xanthomonadales:
      Xanthomonadaceae), the causal agent of Pierce's disease of grapevines. Over the
      course of the H. vitripennis lifespan, the red pigment darkens and eventually
      becomes brown/black in color. These pigments are believed to be pheomelanin and
      eumelanin, respectively. The age of H. vitripennis can be determined by
      calculating the amount of red pigment found in the wings by analyzing high
      resolution wing photographs with image analysis software. In this study, a
      standard curve for the age determination of H. vitripennis was developed using
      laboratory-reared insects of known ages varying from 1 to 60 days. The impact of
      three environmental conditions on these readings was also investigated and found
      to have little effect on the age determination, and could be easily accounted
      for. Finally, field collected insects from several Central Texas vineyards were
      successfully analyzed for age determination suggesting that the annually reported
      influx of H. vitripennis was composed almost entirely of older insects.

PMID- 21870965
TI  - Intrinsic and synthetic stable isotope marking of tsetse flies.
AB  - The sterile insect technique has been successfully used to eliminate tsetse
      populations in a number of programs. Program monitoring in the field relies on
      the ability to accurately differentiate released sterile insects from wild
      insects so that estimates can be made of the ratio of sterile males to wild
      males. Typically, released flies are marked with a dye, which is not always
      reliable. The difference in isotopic signatures between wild and factory-reared
      populations could be a reliable and intrinsic secondary marker to complement
      existing marking methods. Isotopic signatures are natural differences in stable
      isotope composition of organisms due to discrimination against the heavier
      isotopes during some biological processes. As the isotopic signature of an
      organism is mainly dependent on what it eats; by feeding factory-reared flies
      isotopically different diets to those of the wild population it is possible to
      intrinsically mark the flies. To test this approach unlabeled samples of Glossina
      pallidipes (Austen) (Diptera: Glossinidae) from a mass rearing facility and wild
      populations were analyzed to determine whether there were any natural differences
      in signatures that could be used as markers. In addition experiments were
      conducted in which the blood diet was supplemented with isotopically enriched
      compounds and the persistence of the marker in the offspring determined. There
      were distinct natural isotopic differences between factory reared and wild tsetse
      populations that could be reliably used as population markers. It was also
      possible to rear artificially isotopically labeled flies using simple technology
      and these flies were clearly distinguishable from wild populations with greater
      than 95% certainty after 85 days of "release". These techniques could be readily
      adopted for use in SIT programs as complimentary marking techniques.

PMID- 21870966
TI  - Effects of climate change on subterranean termite territory size: a simulation
      study.
AB  - In order to study how climate change affects the territory size of subterranean
      termites, a lattice model was used to simulate the foraging territory of the
      Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera:
      Rhinotermitidae), and the minimized local rules that are based on empirical data
      from the development of termites' foraging territory was applied. A landscape was
      generated by randomly assigning values ranging from 0.0 to 1.0 to each lattice
      site, which represented the spatially distributed property of the landscape. At
      the beginning of the simulation run, N territory seeds - one for each founding
      pair, were randomly distributed on the lattice space. The territories grew during
      the summer and shrank during the winter. In the model, the effects of climate
      change were demonstrated by changes in two variables: the period of the summer
      season, T, and the percentage of the remaining termite cells, sigma, after the
      shrinkage. The territory size distribution was investigated in the size
      descending order for the values of T (= 10, 15, ... , 50) and sigma (= 10, 15,
      ... , 50) at a steady state after a sufficiently long time period. The
      distribution was separated into two regions: the larger-sized territories and the
      smaller-sized territories. The slope, m, of the distribution of territory size on
      a semi-log scale for the larger-sized territories was maximal with T (45 <= T <=
      50) in the maximal range and with sigma in the optimal range (30 <= sigma <= 40),
      regardless of the value of N. The results suggest that the climate change can
      influence the termite territory size distribution under the proper balance of T
      and sigma in combination.

PMID- 21870967
TI  - Host preference between symbiotic and aposymbiotic Aphis fabae, by the aphid
      parasitoid, Lysiphlebus ambiguus.
AB  - Few empirical studies have directly explored the association between Buchnera
      aphidicola (Enterobacteriales: Enterobacteriaceae), the primary endosymbiont of
      aphids, and the life history strategies of aphid parasitoids. A series of paired
      choice experiments were conducted to explore the preference of the parasitoid
      Lysiphlebus ambiguus Halliday (Hymenoptera: Aphididae) for symbiotic and
      aposymbiotic Aphis fabae Scopoli (Hemiptera: Aphididae) and the suitability of
      these hosts for parasitoid development. When given a choice between symbiotic and
      aposymbiotic aphids of the same instar, the parasitoid significantly preferred
      symbiotic over aposymbiotic aphids only during the later instars (L(4) and
      adult). The suitability of aposymbiotic aphids for parasitoid development was
      equal to that of symbiotic aphids in terms of survivorship and sex ratio, but was
      significantly lower than that of symbiotic aphids for L(4) and adult instars in
      development rate and/or female adult size. When given a choice between similar
      sized symbiotic L(2) and aposymbiotic L(4) aphids, the parasitoid preferred the
      former. No significant differences in preference or host suitability were
      demonstrated when the parasitoid was given a choice between different instars of
      aposymbiotic aphids. While parasitoid lifetime fecundity increased with aphid
      instar at the time of oviposition, there was no significant influence of previous
      development from symbiotic versus aposymbiotic aphids. These results suggest that
      while L. ambiguus can discriminate between symbiotic and aposymbiotic A. fabae
      during later instars and when the aphids are of a similar size, the primary
      endosymbiont is not needed for successful parasitoid development; and its absence
      only compromises parasitoid growth reared from later instar aposymbiotic host.

PMID- 21870968
TI  - Histological estimates of ovariole number in honey bee queens, Apis mellifera,
      reveal lack of correlation with other queen quality measures.
AB  - Published estimates of the number of ovarioles found in the ovaries of honey bee,
      Apis mellifera L. (Hymenoptera: Apidae) queens range from 100 to 180 per ovary.
      Within the context of a large-scale study designed to assay the overall quality
      of queens obtained from various commercial sources, a simple histology-based
      method for accurate determination of ovariole number was developed and then
      applied to a sample of 75 queens. Although all 10 commercial sources evaluated
      provided queens with ovariole numbers within the expected range, ovariole number
      was found to vary significantly across sources. Overall, and within most of the
      individual samples, there was no correlation of ovariole number with other
      morphological attributes such as thoracic width, wing length, or wet weight.
      Queens from two of the sources, however, displayed a significant negative
      relationship between wet weight and ovariole number. This study provides baseline
      data on ovariole number in commercial honey bee queens in the United States at a
      time when honey bee populations are declining; the method described can be used
      in studies relating ovariole number in queens to egg production and behavior.

PMID- 21870969
TI  - Temperature studies with the Asian citrus psyllid, Diaphorina citri: cold
      hardiness and temperature thresholds for oviposition.
AB  - This study was conducted to obtain information on the cold hardiness of the Asian
      citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), in Florida and
      to assess upper and lower temperature thresholds for oviposition. The psyllid is
      an important pest in citrus because it transmits the bacterial pathogens
      responsible for citrus greening disease, Huanglongbing, considered the most
      serious citrus disease worldwide. D. citri was first found in Florida during
      1998, and the disease was discovered during 2005. Little was known regarding cold
      hardiness of D. citri, but Florida citrus is occasionally subjected to notable
      freeze events. Temperature and duration were each significant sources of
      variation in percent mortality of D. citri subjected to freeze events. Relatively
      large percentages of adults and nymphs survived after being exposed for several
      hours to temperatures as low as -5 to -6  degrees C. Relatively large percentages
      of eggs hatched after being exposed for several hours to temperatures as low as 
      8  degrees C. Research results indicated that adult D. citri become cold
      acclimated during the winter through exposure to cooler winter temperatures.
      There was no evidence that eggs became cold acclimated during winter. Cold
      acclimation in nymphs was not investigated. Research with adult D. citri from
      laboratory and greenhouse colonies revealed that mild to moderate freeze events
      were usually nonlethal to the D. citri irrespective of whether they were cold
      acclimated or not. Upper and lower temperature thresholds for oviposition were
      investigated because such information may be valuable in explaining the
      geographic distribution and potential spread of the pest from Florida as well as
      how cooler winter temperatures might limit population growth. The estimated lower
      and upper thresholds for oviposition were 16.0 and 41.6  degrees C, respectively;
      the estimated temperature of peak oviposition over a 48 h period was 29.6 
      degrees C.

PMID- 21870970
TI  - The basic helix-loop-helix transcription factor family in the pea aphid,
      Acyrthosiphon pisum.
AB  - The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range
      of developmental processes in higher organisms. bHLH family members have been
      identified in over 20 organisms, including fruit fly, zebrafish, and human. This
      study identified 54 bHLH family members in the pea aphid, Acyrthosiphon pisum
      (Harris) (Hemiptera: Aphididae), genome. Phylogenetic analyses revealed that they
      belong to 37 bHLH families with 21, 13, 9, 1, 9, and 1 members in group A, B, C,
      D, E, and F, respectively. Through in-group phylogenetic analyses, all of the
      identified A. pisum bHLH members were assigned into their correspondent bHLH
      families with confidence, among which 51 were defined according to phylogenetic
      analyses with orthologs from Drosophila melanogaster Meigen (Diptera:
      Drosophilidae), and 3 of them were defined according to phylogenetic analyses
      with orthologs from Bombyx mori L. (Lepidoptera: Bombycidae) and Tribolium
      castaneum (Herbst) (Coleoptera: Tenebrionidae). Analyses on genomic coding
      regions revealed that the number and average length of introns in A. pisum bHLH
      motifs are higher than those in other insects. The present study provides useful
      background information for future studies on structure and function of bHLH
      proteins in the regulation of A. pisum development.

PMID- 21870971
TI  - Resistance status of the malaria vector mosquitoes, Anopheles stephensi and
      Anopheles subpictus towards adulticides and larvicides in arid and semi-arid
      areas of India.
AB  - Susceptibility studies of malaria vectors Anopheles stephensi Liston (Diptera:
      Culicidae) and An. subpictus Grassi collected during 2004-2007 from various
      locations of Arid and Semi-Arid Zone of India were conducted by adulticide
      bioassay of DDT, malathion, deltamethrin and larvicide bioassay of fenthion,
      temephos, chlorpyriphos and malathion using diagnostic doses. Both species from
      all locations exhibited variable resistance to DDT and malathion from majority of
      location. Adults of both the species were susceptible to Deltamethrin. Larvae of
      both the Anopheline species showed some evidence of resistance to chlorpyriphos
      followed by fenthion whereas susceptible to temephos and malathion.

PMID- 21870972
TI  - Ecology of the scorpion, Microtityus jaumei in Sierra de Canasta, Cuba.
AB  - An assessment of the population dynamics of Microtityus jaumei Armas (Scorpiones:
      Buthidae) on the slopes south of Sierra de Canasta, Guantanamo Province, Cuba
      show an increase in activity over the year (<= 0.05). The activity peak is
      related to the reproductive period from June to November. The abundance of
      scorpions was significantly related to density of the canopy and thickness of the
      substrate.

PMID- 21870973
TI  - Optimizing immunomarking systems and development of a new marking system based on
      wheat.
AB  - Immunomarking systems used to track large-scale movement patterns of insects are
      highly dependent on the efficiency of the enzyme linked imunosorbent assay
      (ELISA) reaction and logistical factors (e.g. concentration of marker applied,
      ability of the marker to wet the insect cuticle, and trapping methods). This
      paper examines ways to increase ELISA efficiency and mediate logistical factors,
      and provides information on a new immunomarking protein based on wheat gluten.
      The present studies on improving efficiency of the ELISA reactions showed that
      specially treated microplate surfaces were needed for soymilk and gluten assays,
      but not for egg albumin and casein assays. Sample dilution was investigated and
      was found to improve the signal/noise (S/N) ratio for the albumin and casein
      assays, but S/N ratios for the gluten and soymilk assays were less sensitive.
      However, for all assays, marked specimens were still detectable even with
      dilutions down to 6% of the original sample, which would allow more tests to be
      run on the same initial sample volume. For the logistical factors, these studies
      showed that marking of an insect by having it walk across a dried residue could
      be virtually eliminated for the casein and soymilk assays when the concentration
      applied was reduced to < 4%, but residues of 0.125% egg that had been aged in the
      field seven days still marked 37.5% of test insects placed on the residues. Also,
      the adjuvant Sylgard((r)) 309 used at 80 ppm enhanced wetting of the insect
      cuticle and had little or no effect on the ELISA reaction, but the wetting agents
      R-11 and Silwet((r)) L-77 were much more likely to negatively affect ELISA
      performance. Five different trapping adhesives were also evaluated and found to
      reduce ELISA efficiency 38-45% for the casein assay and 61-78% for the soymilk
      assay, while the albumin and gluten assays were unaffected. The information
      provided in this paper can be used to help correct for inherent differences in
      marking efficiency of the different proteins by manipulation of sample
      preparation, adjuvants, and concentrations applied.

PMID- 21870974
TI  - Analysis of cathepsin-K activity at tooth and dental implant sites and the
      potential of this enzyme in reflecting alveolar bone loss.
AB  - BACKGROUND: Cathepsin-K is an enzyme involved in bone metabolism which may make
      this feature important for both natural teeth and dental implants. The aims of
      the present study are to comparatively analyze the gingival crevicular fluid
      (GCF)/peri-implant sulcus fluid (PISF) cathepsin-K levels of natural teeth and
      dental implants, and to assess the potential relationship between this
      biochemical parameter and alveolar bone loss around natural teeth and dental
      implants. METHODS: Probing depth, bleeding on probing, gingival index, and plaque
      index clinical parameters were assessed, and GCF/PISF samples were obtained from
      natural teeth/dental implants presenting with either clinical health,
      gingivitis/peri-implant mucositis, or chronic periodontitis/peri-implantitis.
      Cathepsin-K activity levels of 42 GCF samples and 54 PISF samples were
      determined, and marginal bone loss (MBL) measures were calculated from
      digitalized standardized intraoral periapical radiographs obtained from natural
      teeth and dental implants by using cemento-enamel junction and the actual
      distance between two consecutive threads of the dental implant as reference
      points for natural teeth and dental implants, respectively. RESULTS: Comparing
      the natural teeth group with dental implant group with regard to MBL measure,
      cathepsin-K activity, and GCF/PISF volume revealed no significant differences. In
      both natural teeth and dental implant groups, despite higher MBL measures,
      cathepsin-K activity, and GCF/PISF volumes with the presence of inflammation, it
      was the presence of alveolar bone loss that lead to significantly higher values
      for these parameters. CONCLUSION: We suggest cathepsin-K as a biochemical
      parameter for monitoring periodontal/peri-implant alveolar bone loss.

PMID- 21870975
TI  - Surgical microscope may enhance root coverage with subepithelial connective
      tissue graft: a randomized-controlled clinical trial.
AB  - BACKGROUND: Minimally invasive techniques have broadened the horizons of
      periodontal plastic surgery to improve treatment outcomes. Thus, the purpose of
      this clinical trial was to compare root coverage, postoperative morbidity, and
      esthetic outcomes of subepithelial connective tissue graft (SCTG) technique with
      or without the use of a surgical microscope in the treatment of gingival
      recessions. METHODS: In this split-mouth study, twenty-four patients with
      bilateral Miller's Class I or II buccal gingival recessions >=2.0 mm in canines
      or premolars were selected. Gingival recessions were randomly designated to
      receive treatment with SCTG with or without the assistance of the surgical
      microscope (test and control groups, respectively). Clinical parameters evaluated
      included the following: depth (RH) and width (RW) of the gingival defect, width
      (WKT) and thickness (TKT) of keratinized tissue, probing depth (PD), and clinical
      attachment level (CAL). Postoperative morbidity was evaluated by means of an
      analog visual scale and questionnaire. Patient satisfaction was also evaluated
      with a questionnaire. Descriptive statistics were expressed as mean +/- SD.
      Repeated-measures analysis of variance was used for examination of differences
      regarding PD, CAL, and TKT. The Wilcoxon test was used to detect differences
      between groups and the Friedman test to detect differences within group regarding
      WKT, RH, and RW. RESULTS: The average percentages of root coverage for test and
      control treatments, after 12 months, were 98.0% and 88.3%, respectively (P
      <0.05). Complete root coverage was achieved in 87.5% and 58.3% of teeth treated
      in test and control groups, respectively. For all parameters except recession
      height, there was an improvement in the final examination but without difference
      between treatments. For the RH, a lower value was found in the test group
      compared to the control group (P <0.05). In the test group, all patients were
      satisfied with the esthetics obtained, and 19 patients (79.1%) were satisfied in
      the control group. For postoperative morbidity, 14 patients in each of the two
      treatment groups did not use analgesics for pain control. CONCLUSION: Both
      approaches were capable of producing root coverage; however, use of the surgical
      microscope was associated with additional clinical benefits in the treatment of
      teeth with gingival recessions.

PMID- 21870976
TI  - Group of serum inflammatory markers and periodontitis-metabolic syndrome
      coexistence in Koreans.
AB  - BACKGROUND: Recent epidemiologic studies have shown that individuals with
      periodontitis have a significantly increased risk of metabolic syndrome (MetS).
      Chronic infection and subsequent production of systemic inflammatory markers may
      be associated with this increased risk. The aim of present study is to determine
      whether the presence of periodontitis and MetS is associated with a group or an
      individual of C-reactive protein (CRP), interleukin (IL)-1beta, IL-6, IL-8, tumor
      necrosis factor-alpha (TNF-alpha), and homocysteine (HCY) in the serum of a
      Korean population. METHODS: Medical and periodontal parameters, including CRP, IL
      1beta, IL-6, IL-8, TNF-alpha, and HCY, were evaluated in 118 individuals (73
      healthy; 20 with periodontitis only; 13 with MetS only; and 12 with both). The
      community periodontal index was used to assess periodontitis. Age, sex, monthly
      household income, smoking, and drinking were evaluated as confounders. Analysis
      of covariance, linear regression analysis, and factor analysis were applied.
      RESULTS: The group of serologic cytokines was synergistically associated with the
      periodontitis-MetS coexistence. TNF-alpha and IL-6 were two representing
      serologic cytokines in the group. CONCLUSIONS: Our results suggest that a group
      of systemic biologic markers represented by TNF-alpha and IL-6 might mediate the
      association between MetS and periodontitis adjusted for various confounders.
      Additional evidence is needed to generalize our results more widely.

PMID- 21870977
TI  - A new era for anticoagulation in atrial fibrillation.

PMID- 21870979
TI  - Omega-3 fatty acids do not improve endothelial function in virologically
      suppressed HIV-infected men: a randomized placebo-controlled trial.
AB  - Omega-3 fatty acids decrease cardiovascular disease (CVD) mortality possibly due
      to antiinflammatory effect. Inflammation and endothelial dysfunction likely play
      a role in the heightened CVD risk in HIV. Our goal was to evaluate the effect of
      omega-3 fatty acids primarily on endothelial function and inflammation in HIV
      infected adults with moderate CVD risk on stable antiretroviral therapy. We
      conducted a 24-week, randomized, double-blind, placebo-controlled study to
      evaluate the effect of omega-3-acid ethyl esters 1 g twice a day. Flow-mediated
      dilation (FMD) of the brachial artery, lipoproteins and markers of inflammation,
      endothelial activation, coagulation, and insulin resistance were measured at
      entry and week 24. There were no within- or between-group differences in change
      in FMD over 24 weeks (mean change in FMD -0.13% vs. 1.5% for treatment vs.
      placebo; p=0.21). There were no between-group differences in changes in
      lipoprotein levels or biomarkers tested, except soluble tumor necrosis factor
      receptor-I, which favored omega-3-acid ethyl esters. Omega-3 fatty acids did not
      improve endothelial function or activation, coagulation, or insulin resistance in
      virologically suppressed, HIV-infected men with moderate CVD risk; however,
      inflammation tended to improve. This suggests that omega-3 fatty acids may not be
      potent enough to counteract the enhanced inflammation and endothelial dysfunction
      due to HIV and antiretrovirals.

PMID- 21870980
TI  - Fifty-year trend towards suppression of Wolbachia-induced male-killing by its
      butterfly host, Hypolimnas bolina.
AB  - Some intracellular symbionts of arthropods induce a variety of reproductive
      alterations in their hosts, and the alterations tend to spread easily within the
      host populations. A few cases involving the spread of alteration-inducing
      Wolbachia bacteria in natural populations with time have been reported, but the
      investigations on the increasing trend in counteracting the bacterial effect on
      hosts in natural populations (i.e., increased resistance in hosts against the
      alterations) have been limited. In the present study, the prevalence of an
      alteration, killing of male Hypolimnas bolina (L.) (Lepidoptera: Nymphalidae)
      butterflies by their inherited Wolbachia strain in the wild in Japan, was
      surveyed over a continuous 50-year period, which is far longer than ever before
      analyzed in studies of dynamics between reproductive alteration-inducing
      symbionts and their host arthropods. Thus, the results in this study provide the
      first instance of a long-term trend involving a change in reproductive
      alteration; and it strongly suggests a change in the opposite direction (i.e.,
      suppression of male-killing) in natural populations. This change in the current
      combination of the Wolbachia and butterflies appears to be dependent upon the
      host taxon (race).

PMID- 21870981
TI  - Effects of chitin and contact insecticide complexes on rove beetles in commercial
      orchards.
AB  - A five-year research project was performed to explore the potential effects of
      contact insecticide applications on the change of abundance and species richness
      of predatory rove beetles (Coleoptera: Staphylinidae) in conventionally managed
      orchards. Twelve blocks of nine orchards were used for this study in Central
      Europe. High sensitivity atomic force microscopic examination was carried out for
      chitin structure analyses as well as computer simulation for steric energy
      calculation between insecticides and chitin. The species richness of rove beetles
      in orchards was relatively high after insecticide application. Comparing the mean
      abundance before and after insecticide application, a higher value was observed
      before spraying with alphacypermethrin and lambda-cyhalothrin, and a lower value
      was observed in the cases of diflubenzuron, malathion, lufenuron, and phosalone.
      The species richness was higher only before chlorpyrifos-methyl application.
      There was a negative correlation between abundance and stability value of chitin
      insecticides, persistence time, and soil absorption coefficients. Positive
      correlation was observed with lipo- and water solubility.

PMID- 21870982
TI  - CpG methylation in the hexamerin 110 gene in the European honeybee, Apis
      mellifera.
AB  - The European honeybee, Apis mellifera L. (Hymenoptera: Apidae), has a full set of
      machinery for functional CpG methylation of its genome. A recent study
      demonstrated that DNA methylation in the honeybee is involved in caste
      differentiation. In this study, the expression and methylation of the hexamerin
      110 gene (Hex110), which encodes a storage protein, was analyzed. High levels of
      the Hex110 transcript were expressed in both worker and queen larvae. Low levels
      of this transcript were also detected in adult fat bodies, and the expression
      level was higher in the queen than in the worker. Bisulfite sequencing revealed
      that the Hex110 gene is overall methylated at a low level, with a limited number
      of CpG sites methylated at relatively high levels. These highly methylated sites
      were exclusively located in the exon regions. The average methylation rate of the
      Hex110 gene was higher in the adult stage than in the larval stage. Furthermore,
      several CpG sites were differentially methylated between the worker and queen
      larvae. These observations suggest that the methylation of the Hex110 gene is
      regulated at the developmental stage and in a caste-dependent manner.

PMID- 21870983
TI  - First record of the genus Zygina from a Neotropical region on Populus spp.:
      taxonomic and biological characteristics.
AB  - The typhlocybine, Zygina nivea Mulsant & Rey 1855, was found in urban areas of
      Argentina colonizing trees of poplar (Populus alba L. and P. nigra L.). This is
      the first mention of the genus Zygina Fieber from the Neotropical region. In this
      paper redescription of the male, description of the female, distributional and
      host plant data, and behavioural observations of this species are given.

PMID- 21870984
TI  - Diversity and seasonal dynamics of an assemblage of sarcophagid Diptera in a
      gradient of urbanization.
AB  - Sarcophagid species inhabiting different locations in a rural-urban gradient were
      surveyed in the east central Argentine district of the Almirante Brown, Buenos
      Aires province. The main objectives of this research were to identify the most
      prevalent sarcophagid species and to describe community richness and diversity
      according to the degree of urbanization and the environmental variables measured
      in three locations within a rural-urban gradient sampled during two years from
      May 2005 to April 2007. Spatial and seasonal variations were the main factors
      involved in structuring the sarcophagid communities. Diversity was lower in
      urbanized areas than in rural ones. Bait and microhabitat preferences (sunny or
      shady places) and seasonal fluctuations were described for 17 sarcophagid
      species.

PMID- 21870985
TI  - A review of the planthopper genus Armacia Stal (Hemiptera: Fulgoromorpha:
      Ricaniidae) with descriptions of four new species from Indonesia and Papua New
      Guinea.
AB  - The genus Armacia Stal (Hemiptera: Fulgoromorpha: Ricaniidae) is reviewed
      taxonomically. Four new species of the genus are described and illustrated from
      West-Pacific region: A. madangensis sp. nov. (Papua New Guinea), A. rubilimba sp.
      nov. (Indonesia), A. spinae sp. nov. (Indonesia) and A. vigorata sp. nov.
      (Indonesia), A. albipes (Walker 1868), A. clara (Stal 1859), A. divisura (Walker
      1868), A. fusca Melichar 1898, A. hyalinata (Donovan 1805), A. latipennis (Walker
      1868), A. nigrifrons (Walker 1858), A. simaethis Fennah 1956 , and A. spatiosa
      (Walker 1868) are redescribed and illustrated. A checklist of all known species
      and a diagnosis of the genus are provided. A key to all species in the genus is
      provided.

PMID- 21870986
TI  - Intra and inter-population morphological variation of shape and size of the
      Chilean magnificent beetle, Ceroglossus chilensis in the Baker River Basin,
      Chilean Patagonia.
AB  - The alteration of habitat generates different degrees of stress in insects. It
      has been suggested that the degrees of phenotypic disturbances reflect the
      ability of an individual to overcome the effects of stress. The Baker River Basin
      in the Aysen Region, Chilean Patagonia has a very fragmented landscape, due to
      the destruction of the native forest and the use of land for agriculture and
      animal husbandry. This alteration should generate different degrees of
      disturbances in the insect communities, whose effects may be quantified by
      geometric morphometric tools. We analyzed morphological differences in 244 males
      and 133 females of the the Chilean magnificent beetle, Ceroglossus chilensis
      (Eschscholtz) (Coleoptera: Carabidae) collected in January, 2007, in mixed
      forests of Nothofagus dombeyi Mirbel (Orsted) (Fagales: Nothofagaceae) and N.
      nitida Hofmus and in Second-growth forest of N. pumilio (Poepp. & Endl.) Krasser.
      Males were generally wider in the pronotum, while females had wider abdominal
      sternites. Although there were significant differences in shape and size between
      mature forests and second-growth forest, these were less significant among the
      sites within each type of vegetal formation. Individuals had more shape
      variations in the mature forest. We suggest that differences in shape are due at
      least in part to the isolation of the habitat. The differences found between
      sexes raises the question of how morphological variations and sexual dimorphism
      may be affected spatially by natural selection.

PMID- 21870988
TI  - Multiple births: an update.

PMID- 21870987
TI  - Oosorption in the endoparasitoid, Pteromalus puparum.
AB  - Oosorption is the resorption of oocytes in the ovaries, and is usually induced by
      environmental stress. It has been demonstrated in some insect species, but
      overall the mechanisms of oosorption are poorly understood. In this study, the
      oosorption in the endoparasitic wasp, Pteromalus puparum L. (Hymenoptera:
      Pteromalidae), was observed in response to starvation. To explore the details of
      oosorption in P. puparum, both levels of hemolymph vitellogenin and ovarian
      vitellin were determined using sandwich ELISA. The results indicated that both
      levels of vitellin and total protein in the ovaries were significantly decreased
      48 h after eclosion in starved P. puparum, while those of vitellogenin and total
      protein in the hemolymph were increased. In addition, observation of the
      ultrastructure of mature oocytes in the ovarioles revealed changes in yolk
      protein content. Those protein yolk spheres and lipid yolk spheres that had
      accumulated in the oocytes, were transferred out of the oocytes of starved
      females. It was assumed that once oosorption was induced in P. puparum, vitellin
      in the oocytes was transported outside and released into the hemolymph. This
      information helps to elucidate a mechanism of oosorption in insects.

PMID- 21870989
TI  - Multiple births from fertility treatment in the UK: a consensus statement.

PMID- 21870990
TI  - Toward developing a training pathway for fertility nurses: report of the 2010
      training and educational survey.
AB  - Fertility nursing and its role extension has increasingly been referred to as
      'specialist' or 'advanced nursing practice'. Nevertheless, Government initiatives
      have prompted a review of 'Advanced Nursing Practice' and the Nursing & Midwifery
      Council (NMC) has taken steps to address the disparity of roles, job titles,
      training and competence of nurse practitioners, concluding that advanced nursing
      practice should be subject to revalidation in the same way as professional
      registration. Fertility nurses form an integral part of the multidisciplinary
      team. Yet no formal or nationally recognised framework or training pathway
      exists. In this paper, we present the findings of a recent online survey of
      training and educational needs of fertility nurses; its aim being to work toward
      developing a national training pathway. Our findings identify the relationship
      between fertility nurse competencies, advanced nursing practice and medical sub
      specialist training, at the same time, highlighting the difference in
      accessibility, funding and levels of training, as well as assessment and
      expertise within clinical practice. We conclude that it is essential to protect
      role extension through regonised Higher Educational Institution (HEI)
      accreditation, by appropriate, role-focussed training. Notwithstanding a national
      review, the diverse list of job titles also needs to be addressed adequately to
      encompass and respect role extension.

PMID- 21870994
TI  - Potential clinical insights into microRNAs and their target genes in esophageal
      carcinoma.
AB  - Esophageal carcinoma (EC) are characterized by dysregulation of microRNAs, which
      play an important roles as a posttranscriptional regulators in protein synthesis,
      and are involved in cellular processes, such as proliferation, apoptosis, and
      differentiation. Recently, altered miRNAs expression has been comprehensively
      studied in EC by high-throughput technology. Increased understanding of miRNAs
      target genes and their potential regulatory mechanisms have clarified the miRNAs
      activities and may provide exciting opportunities for cancer diagnosis and miRNA
      based genetherapy. Here, we reviewed the most recently discovered miRNA target
      genes, with particular emphasis on the deciphering of their possible mechanisms
      and the potential roles in miRNAs-based tumour therapeutics.

PMID- 21870995
TI  - Therapeutic targeting of B7-H1 in breast cancer.
AB  - INTRODUCTION: Breast cancer is the most common form of malignancy occurring in
      women worldwide. B7-H1 is a co-inhibitory molecule expressed by several types of
      tumors, including breast cancer. The aberrant expression of B7-H1 in breast
      cancer cells has been determined, its role in recruiting regulatory T cells into
      the tumor microenvironment has been elucidated and a strong link to B7-H1
      induction in highly proliferative breast cancer has been provided. It has also
      been demonstrated that doxorubicin, a drug commonly used for breast cancer
      treatment, downregulates the cell surface expression of B7-H1 and upregulates its
      nuclear expression, which therefore suggests an anti-apoptotic role of B7-H1 in
      breast cancer. AREAS COVERED: This review illustrates the various factors
      involved in the induction of B7-H1 and its role in immune evasion and
      chemoresistance. It also provides potential therapeutic strategies for targeting
      B7-H1 in breast cancer. EXPERT OPINION: B7-H1 should be considered as a potential
      therapeutic target for breast cancer. Indeed, there is increasing evidence for
      the potential efficacy of B7-H1 blockade in the prevention of immune evasion by
      cancer cells. Additionally, B7-H1 targeting can be used in conjunction with other
      therapeutic modalities for improved efficacy and reduced toxicity. We expect that
      B7-H1 blockade in combination with other therapeutics will be a prime therapeutic
      strategy in the future.

PMID- 21870996
TI  - Lethal iron deprivation induced by non-neutralizing antibodies targeting
      transferrin receptor 1 in malignant B cells.
AB  - A number of antibodies have been developed that induce lethal iron deprivation
      (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing
      transferrin (Tf) binding, blocking internalization of the receptor and/or
      inducing its degradation. We have developed recombinant antibodies targeting
      human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are
      cytotoxic to certain malignant B-cells. We now show that internalization of TfR1
      bound to these antibodies can lead to its sequestration and degradation, as well
      as reduced Tf uptake, and the induction of a transcriptional response consistent
      with iron deprivation, which is mediated in part by downstream targets of p53.
      Cells resistant to these antibodies do not sequester and degrade TfR1 after
      internalization of the antibody/receptor complex, and accordingly maintain their
      ability to internalize Tf. These findings are expected to facilitate the rational
      design and clinical use of therapeutic agents targeting iron import via TfR1 in
      hematopoietic malignancies.

PMID- 21870997
TI  - Factors contributing to impaired self-awareness of cognitive functioning in an
      HIV positive and at-risk population.
AB  - PURPOSE: To examine the association between self-awareness of cognitive
      impairment and age, selected mood disorders, and type and severity of cognitive
      impairment in a sample of individuals with HIV/AIDS and at risk for HIV. METHOD:
      75 subjects, 52 HIV+ and 23 at risk for HIV completed a psychosocial interview,
      the Patient's Assessment of Own Functioning (PAOF) questionnaire, and a battery
      of neuropsychological tests. Based upon the differences between their clinical
      impairment and self-reported impairment, subjects were classified as being
      "Underestimators", "Good Awareness", or "Impaired Awareness" with regard to self
      awareness. RESULTS: Those with more severe cognitive impairment were less aware
      than those with normal or borderline cognitive impairment. A one-way ANOVA
      suggested that the Impaired Awareness group differed significantly from the
      Underestimators on the Rey Figure Immediate and Delayed Recall tasks, and from
      both the Underestimators and Good Awarenesss groups on the Digit Symbol
      Substitution Task. There were significant differences among all awareness groups
      on the test of Simple Reaction Time. Furthermore there is some suggestion that
      age may contribute to impaired self-awareness. The role of HIV in self-awareness
      remains unclear, as both, individuals with HIV and at risk, demonstrated impaired
      self-awareness. CONCLUSIONS: Overall, impaired awareness was associated with
      poorer test performance, suggesting a relationship between awareness and
      sustained complex attention and visual spatial processing. This research has
      implications for understanding factors contributing to poor awareness among
      individuals with cognitive impairment.

PMID- 21870998
TI  - Comparison of venous and arterial blood sampling for the assessment of platelet
      aggregation with whole blood impedance aggregometry.
AB  - Platelet monitoring is presently under evaluation in the clinic as a tool to
      improve antiplatelet treatment in patients with coronary artery disease (CAD).
      Measuring platelet function has, however, many inherent problems. It is important
      not only to evaluate the method used, but also to evaluate and standardize
      sampling and sample handling. As platelet monitoring is often performed in
      connection to coronary angiography and percutaneous coronary interventions,
      arterial sampling may be more convenient. However, in the outpatient follow-up
      setting venous sampling is, for obvious reasons, more practical and convenient.
      In the present study we compared platelet aggregation in blood collected from the
      arterial sheath to blood collected from the antecubital vein using multiple
      electrode aggregometry in whole blood in 28 patients with CAD. We found that
      sampling from artery and vein give similar data and that an identical number of
      patients with insufficient antiplatelet responses ('low responders' to aspirin
      and clopidogrel, respectively, according to predefined criteria) were detected
      with respect to adenosine diphosphate induced and arachidonic-acid induced
      aggregation. Thus both arterial and venous blood samples can be used in the
      monitoring of platelet function when multiple electrode aggregometry is applied
      to detect 'low responders'.

PMID- 21870999
TI  - Parkinson-like features in ALS with predominant upper motor neuron involvement.
AB  - Owing to the frequent observation of poverty of movements, facial hypomimia and
      balance impairment, amyotrophic lateral sclerosis (ALS) variant with predominance
      of upper motor neuron involvement (UMN-ALS) is prone to be diagnosed with
      Parkinsonism. A clinical assessment, including the velocity-dependent stretch
      response test to differentiate between pyramidal and extrapyramidal stiffness;
      the Unified Parkinson's Disease Rating Scale and the Berg Balance Scale to assess
      degree of bradykinesia and postural instability; and (123)I-FP-CIT scintigraphy
      evaluation to investigate the nigrostriatal circuit involvement, were carried out
      to characterize Parkinson-like features in UMN-ALS patients. Sixteen UMN-ALS
      patients were included in the study. The velocity-dependent stretch response
      indicated spasticity in all the muscles tested. The degree of stiffness was found
      to be related to bradykinesia and postural instability. Eleven patients (70%)
      showed a reduction in striatal (123)I-FP-CIT uptake found to be related to
      disease duration and patients' ages but not to scores of the functional scales.
      Slowness of movements and postural instability noted in our patients could be
      mostly attributed to spasticity. The lack of any correlation between UPDRS or BBS
      scores and the degree of nigrostriatal impairment on DaTSCAN seems to disprove
      nigrostriatal circuit involvement in these extrapyramidal-like features.

PMID- 21871000
TI  - Molecules modulating gene transcription during muscle wasting in cancer, sepsis,
      and other critical illness.
AB  - Muscle wasting in patients with sepsis, severe injury, and cancer is associated
      with increased transcription of several genes regulating different proteolytic
      pathways. The involvement of gene activation in muscle wasting suggests that
      transcription factors and nuclear cofactors play important roles in the
      regulation of muscle mass. Among transcription factors, NF-kappaB, C/EBPbeta, and
      FOXO transcription factors are activated in atrophying muscle and stimulate the
      transcription of genes in the ubiquitin-proteasome proteolytic pathway, as well
      as genes regulating authophagy/lysosomal proteolysis. Changes in the expression
      and activity of several nuclear cofactors, including the histone
      acetyltransferase p300, histone deacetylases (HDACs), such as HDAC3, HDAC6, and
      SIRT1, as well as the nuclear cofactors PGC-1alpha and beta, contribute to loss
      of muscle mass in various catabolic conditions. The activity of transcription
      factors and nuclear cofactors involved in the regulation of muscle mass is
      influenced not only by their abundance, but also by posttranslational
      modifications as well, including ubiquitination, phosphorylation, and
      acetylation. Transcription factors and nuclear cofactors involved in muscle
      wasting interact with each other at multiple levels, supporting the concept that
      the molecular regulation of muscle mass in various catabolic conditions is
      complex. An increased understanding of molecules that modulate gene transcription
      in catabolic muscle may make it possible to develop treatments targeting
      transcription factors and nuclear cofactors in the prevention and treatment of
      muscle wasting.

PMID- 21871001
TI  - Immunochemically unreactive albumin in urine: fiction or reality?
AB  - Urinary albumin measurements are currently not standardized due to a lack of a
      reference method and reference (primary and secondary [matrix]) material.
      Multiple molecular forms of albumin in urine are identified. Modification of
      albumin by proteolysis during passage through the urinary tract and chemical
      modification during specimen storage leads to the formation of albumin fragments.
      Multiple methods have been developed to quantify albuminuria and significant
      different results are reported dependent on the available assay. The current
      point of view of the National Kidney Disease Education Program - IFCC Working
      Group on Standardization of Albumin considers the immunoassay with polyclonal
      sera as the primary method of quantifying urine albumin. This article reviews the
      process of albumin fragmentation and focuses on the controversial topic of immuno
      unreactive, nonimmunoreactive, or immunochemically nonreactive albumin fractions
      and its consequences for albumin analysis. We conclude that at present there are
      no hard arguments for measuring immunochemically unreactive albumin in urine.
      Immunoassays using polyclonal antisera for the detection of urinary albumin
      remain the gold standard. The development of a reference measurement procedure
      remains one of the challenges for the future.

PMID- 21871002
TI  - Clinical relationship between Hashimoto's thyroiditis and papillary thyroid
      cancer.
AB  - BACKGROUND: The relationship between Hashimoto's thyroiditis (HT) and papillary
      thyroid cancer (PTC) with regard to their co-occurrence and the effect of
      concurrent HT on the prognosis of PTC has been debated. The aim of the present
      study is to determine a clinical relationship between these two disease entities
      and to evaluate the correlation between concurrent HT and various
      clinicopathological parameters. MATERIAL AND METHODS: Demographic and
      histopathological data were collected from 675 patients undergoing thyroid
      surgery from 2000 to 2005, and 303 patients who received initial treatment for
      thyroid disease at our institution and whose medical records were accessible for
      review were enrolled in this study. Of these participants, 269 with
      histologically confirmed PTC were analysed according to the presence or absence
      of concurrent HT. RESULTS: Of 269 patients with PTC, 21.6% (58/269) had
      concurrent HT, whereas only 5.9% (2/34) had concurrent HT with another diagnosis
      (p = 0.031, odds ratio = 4.4; 95% CI, 1.02-18.90). Younger age at presentation
      and a greater female preponderance were noted in patients with HT compared with
      those without HT (p = 0.008 and p = 0.009, respectively). Although it was not
      statistically significant, PTC with HT patients tented to have smaller tumour
      size (1.6 +/- 1.0 cm vs. 1.8 +/- 1.5 cm), lower incidence of lymph node
      metastasis at presentation (12.2% vs. 29.9%), unifocal disease (84.5% vs. 78.7%),
      and early-stage disease. Additionally, PTC with HT patients exhibited better
      prognosis, viewed in recurrence and mortality, during the 62-month mean follow-up
      period. DISCUSSION: HT was definitely associated with PTC as was chronic
      inflammation with cancer in other locations. Interestingly, however, the
      coexistence of HT in PTC cases introduced favourable clinical outcomes compared
      with those of PTC without HT.

PMID- 21871003
TI  - Dose prescription and treatment planning based on FMISO-PET hypoxia.
AB  - PURPOSE: The study presents the implementation of a novel method for
      incorporating hypoxia information from PET-CT imaging into treatment planning and
      estimates the efficiency of various optimization approaches. Its focuses on the
      feasibility of optimizing treatment plans based on the non-linear conversion of
      PET hypoxia images into radiosensitivity maps from the uptake properties of the
      tracers used. MATERIAL AND METHODS: PET hypoxia images of seven head-and-neck
      cancer patients were used to determine optimal dose distributions needed to
      counteract the radiation resistance associated with tumor hypoxia assuming
      various scenarios regarding the evolution of the hypoxic compartment during the
      treatment. A research planning system for advanced studies has been used to
      optimize IMRT plans based on hypoxia information from patient PET images. These
      resulting plans were compared in terms of target coverage for the same fulfilled
      constraints regarding the organs at risk. RESULTS: The results of a planning
      study indicated the clinical feasibility of the proposed method for treatment
      planning based on PET hypoxia. Antihypoxic strategies would lead to small
      improvements in all the patients, but higher effects are expected for the
      fraction of patients with hypoxic tumors. For these, individualization of the
      treatment based on hypoxia PET imaging could lead to improved treatment outcome
      while creating the premises for limiting the irradiation of the surrounding
      normal tissues. CONCLUSIONS: The proposed approach offers the possibility of
      improved treatment results as it takes into consideration the heterogeneity and
      the dynamics of the hypoxic regions. It also provides early identification of the
      clinical cases that might benefit from dose escalation as well as the cases that
      could benefit from other counter-hypoxic measures.

PMID- 21871004
TI  - Validation of histological diagnoses in a national cervical screening register.
AB  - BACKGROUND: Monitoring and evaluation of cancer screening programmes require
      accurate data on invitations, visits, test results, diagnoses and management. The
      purpose of this study was to evaluate the completeness and accuracy of
      histological diagnoses (cervical precancerous lesions and cancer) in the Finnish
      cervical cancer screening register by comparing data with the cancer register and
      the administrative hospital discharge register. MATERIAL AND METHODS: Screening
      data covering all 16 353 screening episodes that resulted in a referral for
      colposcopy over the period of 1998-2007 were individually linked with hospital
      discharge and cancer register data using the unique personal identifier.
      Agreement between registers, as well as sensitivity, coverage and positive
      predictive values (PPV) for the screening register and the hospital discharge
      register diagnosis, were estimated. Invasive cases in the cancer register and
      pooled cases of precancerous lesions were used as reference case populations.
      RESULTS: The sensitivity of the screening register for cervical cancer was 69%,
      the coverage 100% and the PPV 77%. Corresponding values for the hospital
      discharge register were 81%, 100% and 83%, respectively. Sensitivity of the
      screening register for cervical intraepithelial neoplasia grade 2 or worse
      (CIN2+) against the pooled case population was 89% and coverage 99%.
      Corresponding values for the hospital discharge register were 78% and 93%. Kappa
      values for pair-wise agreement between the three registers ranged between 0.73
      and 0.79, often the lesion grade was lower in the screening register than in the
      other two registers. CONCLUSIONS: The data in the screening register has high
      coverage and is thus useful for statistical and evaluation purposes. However, in
      order to improve the accuracy of diagnostic information, there are grounds to
      consider data retrieval through systematic linkage to other health care
      registers.

PMID- 21871005
TI  - Early effects of contemporary breast radiation on health-related quality of life 
      predictors of radiotherapy-related fatigue.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to report on early effects of
      contemporary radiotherapy (RT) on health-related quality of life (HRQOL) and
      explore treatment-related contributors to the development of fatigue during RT in
      breast cancer (BC) patients. MATERIAL AND METHODS: Consecutive BC patients (n =
      248) referred for postoperative RT at St. Olavs University Hospital in Trondheim,
      Norway were enrolled from February 2007 to October 2008. Clinical- and treatment
      data were recorded, and HRQOL were assessed before starting (baseline) and
      immediately after ending RT using the "EORTC QLQ-C30" and the breast module
      "EORTC QLQ-BR23". Change scores from baseline were calculated. Predictors of
      increased fatigue during RT were explored with multiple regression analysis
      adjusted for relevant confounders. RESULTS: The global QOL- and all functional
      scales remained stable, except for "future perspective" which improved
      significantly during RT. Breast symptoms and fatigue increased significantly
      during RT. Groups with elevated baseline fatigue remained more stable during RT
      than those with lower levels at baseline. The body volume receiving 40 Gy or more
      (V40) was a significant predictor of increased fatigue during RT adjusted for
      chemotherapy, comorbidity and age (p = 0.035). CONCLUSION: Contemporary RT has
      limited early effects on HRQOL. V40 is a significant predictor of RT-related
      fatigue.

PMID- 21871006
TI  - Blastic plasmacytoid dendritic cell neoplasm without cutaneous involvement: a
      rare disease with a rare presentation.

PMID- 21871007
TI  - Polycystic kidney disease-like domains of clostridial collagenases and their role
      in collagen recruitment.
AB  - Bacterial collagenases exhibit a multimodular domain organization. While the N
      terminal collagenase unit harbors the catalytic zinc and suffices to degrade
      peptidic substrates, collagen substrates come in different types, explaining the
      requirement for accessory domains such as polycystic kidney disease (PKD)-like
      domains for efficient catalysis. How the recognition and unfolding of (micro
      )fibrillar or triple-helical collagen is accomplished are only poorly understood.
      Here, we present the crystal structure of the PKD-like domain of collagenase G
      from Clostridium histolyticum. The beta-barrel structure reveals a two-tier
      architecture, connected by kinked hinge segments. Together with sheet extension
      as a generic oligomerization mechanism, this explains the cooperativity among
      accessory domains as well as their adaptivity to varying substrates.

PMID- 21871008
TI  - Influenza A virus infection activates cholesterol sulfotransferase (SULT2B1b) in
      the lung of female C57BL/6 mice.
AB  - Cytosolic sulfotransferases (SULTs) catalyze the sulfation of hormones,
      neurotransmitters, and xenobiotics, increasing their water solubility. SULTs are
      not only important for xenobiotic detoxification but they also play important
      biological roles in the regulation of the activities of various biosignaling
      molecules and other cellular functions. In this study, we investigated the
      effects of influenza A virus lung infection on the expression of SULTs in the
      lung, brain, and liver of female C57BL/6 mice. Our results demonstrate for the
      first time that SULT2B1b enzyme activity and protein expression are significantly
      up-regulated in the lung and brain of female mice in response to lung influenza A
      virus infection. Real-time quantitative PCR results are consistent with Western
      blot and enzymatic activity data. In mouse liver, mSULT2B1b is not significantly
      changed. Enzyme activities, protein expression, and mRNA expression of SULT1A1
      and SULT2A1 in the lung, brain, and liver of mice were not significantly affected
      by the infection. The induction of SULT2B1b may be used to inactivate natural
      liver X receptor ligands and activate the proliferation of T cells in response to
      influenza A virus infection in the lung and brain of mice. Our results raise the
      possibility that regulation of SULT2B1b may influence acquired immune responses
      to infectious diseases.

PMID- 21870978
TI  - Apixaban versus warfarin in patients with atrial fibrillation.
AB  - BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in
      patients with atrial fibrillation but have several limitations. Apixaban is a
      novel oral direct factor Xa inhibitor that has been shown to reduce the risk of
      stroke in a similar population in comparison with aspirin. METHODS: In this
      randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice
      daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in
      18,201 patients with atrial fibrillation and at least one additional risk factor
      for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic
      embolism. The trial was designed to test for noninferiority, with key secondary
      objectives of testing for superiority with respect to the primary outcome and to
      the rates of major bleeding and death from any cause. RESULTS: The median
      duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27%
      per year in the apixaban group, as compared with 1.60% per year in the warfarin
      group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to
      0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major
      bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per
      year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001),
      and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard
      ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was
      0.24% per year in the apixaban group, as compared with 0.47% per year in the
      warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate
      of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group
      and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to
      1.13; P=0.42). CONCLUSIONS: In patients with atrial fibrillation, apixaban was
      superior to warfarin in preventing stroke or systemic embolism, caused less
      bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and
      Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

PMID- 21871009
TI  - Fever-like temperature modification differentially affects in vitro signaling of
      bradykinin B(1) and B(2) receptors.
AB  - The bradykinin (BK) B(2) and B(1) receptors (B(2)R, B(1)R) belong to the
      rhodopsin-like G protein-coupled receptors (GPCRs) and are involved in
      (patho)physiological processes such as blood pressure regulation or inflammation.
      They mediate the effects of the pro-inflammatory peptides bradykinin/kallidin and
      desArg(9)-BK/desArg(10)-kallidin, respectively. Whereas the B(2)R is
      constitutively expressed and gets internalized upon activation, the B(1)R is
      especially induced by inflammatory mediators and responds to stimulation with
      increased surface receptor numbers. Stimulation of both receptors activates
      phospholipase Cbeta (PLCbeta) and mitogen activated protein kinase (MAPK)
      signaling. Because inflammatory processes are characterized by heat (fever), we
      analyzed the effect of increased temperature (41 degrees C vs. 37 degrees C) on
      B(1)R and B(2)R signaling in HEK 293 and IMR 90 cells. Our results show that
      signaling of both receptors is temperature-sensitive, however to a different
      extent and with regard to the investigated pathways. Comparing PLCbeta activity
      and Ca(2+)-regulated signals, a temperature-dependent increase was only observed
      for B(1)R but not for B(2)R activation, whereas MAPK activities were doubled at
      41 degrees C for both receptors. Taken together, our findings suggest that the
      observed temperature sensitivity of B(1)R-induced PLCbeta activation is B(1)R
      specific. In contrast, the enhanced stimulation of MAPK activity under
      hyperthermic conditions appears to be a common phenomenon for GPCRs.

PMID- 21871010
TI  - Analysis of the autoproteolytic activity of the recombinant helper component
      proteinase from zucchini yellow mosaic virus.
AB  - The multifunctional helper component proteinase (HC-Pro) of potyviruses contains
      an autoproteolytic function that, together with the protein 1 (P1) and NIa
      proteinase, processes the polyprotein into mature proteins. In this study, we
      analysed the autoproteolytic active domain of zucchini yellow mosaic virus (ZYMV)
      HC-Pro. Several Escherichia coli-expressed MBP:HC-Pro:GFP mutants containing
      deletions or point mutations at either the N- or C-terminus of the HC-Pro protein
      were examined. Our results showed that amino acids essential for the proteolytic
      activity of ZYMV HC-Pro are distinct from those of the tobacco etch virus HC-Pro,
      although the amino acid sequences in the proteolytic active domain are conserved
      among potyviruses.

PMID- 21871011
TI  - Studies of intestinal morphology and cathepsin B expression in a transgenic mouse
      aiming at intestine-specific expression of Cath B-EGFP.
AB  - Cathepsin B has been shown to not only reside within endo-lysosomes of intestinal
      epithelial cells, but it was also secreted into the extracellular space of
      intestinal mucosa in physiological and pathological conditions. In an effort to
      further investigate the function of this protease in the intestine, we generated
      a transgenic mouse model that would enable us to visualize the localization of
      cathepsin B in vivo. Previously we showed that the A33-antigen promoter could be
      successfully used in vitro in order to express cathepsin B-green fluorescent
      protein chimeras in cells that co-expressed the intestine-specific transcription
      factor Cdx1. In this study an analog approach was used to express chimeric
      cathepsin B specifically in the intestine of transgenic animals. No overt
      phenotype was observed for the transgenic mice that reproduced normally.
      Biochemical and morphological studies confirmed that the overall intestinal
      phenotype including the structure and polarity of this tissue as well as cell
      numbers and differentiation states were not altered in the A33-CathB-EGFP mice
      when compared to wild type animals. However, transgenic expression of chimeric
      cathepsin B could not be visualized because it was not translated in situ
      although the transgene was maintained over several generations.

PMID- 21871012
TI  - A pilot safety trial investigating a vector-based vaccine targeting
      carcinoembryonic antigen in combination with radiotherapy in patients with
      gastrointestinal malignancies metastatic to the liver.
AB  - OBJECTIVE: Previous studies have demonstrated the ability of non-lethal doses of
      radiation to alter the phenotype of tumor cells to facilitate immune mediated
      killing. This pilot study evaluated the tolerability of a vector-based vaccine
      targeting carcinoembryonic antigen (CEA) in combination with radiation therapy in
      patients with gastrointestinal malignancies metastatic to the liver. METHODS:
      Patients enrolled had progressive CEA(+) tumors with metastatic liver lesions.
      Patients had received a median of three previous chemotherapy regimens, with a
      median of 2 months since their last chemotherapy regimen. Only 58% had metastatic
      disease limited to the liver. Vaccination commenced day 1 with biweekly boosters
      and split-course radiation (total 32 Gy) starting on day 21. Blood was collected
      at baseline and day 91 for immunological analysis. RESULTS/CONCLUSION: A total of
      12 patients were enrolled. There were no grade 3 or greater toxicities or grade 2
      or greater hepatic toxicities. Median time on-study was 3 months, with the
      longest time on treatment being 5 months (n = 2). Immunological analysis was
      limited to two patients; neither showed an increase above baseline in CEA
      specific T cells post-therapy. CEA/TRICOM vaccination in combination with low
      dose radiation therapy is safe. There was limited evidence of activity in this
      patient population.

PMID- 21871013
TI  - Neonatal morbidity in term neonates is related to gestational age at birth and
      level of care.
AB  - AIMS: The objective of this study was to assess whether the incidence of neonatal
      morbidity of neonates born at term and admitted to a neonatal intensive care unit
      (NICU) differs by gestational age and level of care. METHODS: This is a 5-year
      retrospective cohort study of singleton term births admitted to the NICU of the
      VU University Medical Center with a gestational age >=37+0 weeks. RESULTS: In
      total, 497 neonates were included in the study. The incidence of neonates born
      with an arterial cord blood pH<7.10, neonatal asphyxia, and meconium aspiration
      syndrome increased with advancing gestational age. The incidence of secondary
      cesarean section and operative vaginal delivery also increased with advancing
      gestational age. Neonatal death occurred in 29 (5.84%) of the 497 cases; 27 (93%)
      of 29 were due to asphyxia. Seventeen (34%) of the 50 neonates born in primary
      care were admitted for asphyxia. Eight (47%) of these 17 neonates died.
      CONCLUSIONS: Neonatal morbidity in term neonates is related to gestational age at
      birth. Since asphyxia is an important cause of both morbidity and mortality in
      term neonates, it is important to clearly define and include asphyxia in future
      perinatal audits.

PMID- 21871014
TI  - Nanoparticle-based cerebral drug-delivery systems and antiangiogenic approach in
      gliomas treatment.
AB  - The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas
      is limited by the lack of specific therapies against malignant cells and the
      prognosis in patients affected by cerebral gliomas remains very unfavorable.
      Glial tumors seem to be able to create a favorable environment for the invasion
      of neoplastic cells when they combine with the extracellular matrix through the
      up-regulation of crucial pathways such as angiogenesis and invasion. The major
      problem in brain drug delivery is the presence of the blood brain barrier which
      limits the delivery of many chemotherapeutic agents and other kinds of
      therapeutic molecules. This event often contributes to the failure of the
      treatment. Nanoparticle systems can represent ideal devices for delivery of
      specific compounds to brain tumors across the blood brain barrier. The
      specificity of hybridization makes antisense method an interesting strategy to
      selectively modulate the expression of genes involved in tumorigenesis. In this
      review we will focus on the mechanisms of angiogenesis into gliomas, their
      importance into tumor progression and the possibilities to block these mechanisms
      with new nanoparticle-based therapeutic strategies. We will also report the
      results of preclinical and/or clinical studies that adopt nanoparticle-based
      antiangiogenic therapeutic approach in cerebral gliomas, considering also some
      patents deal with antiangiogenic strategy.

PMID- 21871015
TI  - Current status of inorganic solar cells using quantum structures.
AB  - Thermalization of photogenerated carriers in bulk materials is the main
      bottleneck for the conversion efficiency of conventional inorganic solar cells.
      Furthermore, the achieved conversion efficiency has nearly saturated during the
      last decade despite extensive research. Therefore, new device concepts to break
      through the efficiency barrier are highly requested. Nanotechnologies are the
      building blocks for next-generation solar cells because low-dimensional quantum
      structures can possibly reduce thermalization and extend the light absorption
      range. In addition, very thin nanostructured inorganic solar cells provide us
      with good opportunity to reach highly competitive mass production. Hereafter,
      recently invented inorganic solar cells using quantum structures will be
      reviewed.

PMID- 21871016
TI  - Connective tissue growth factor antagonizes transforming growth factor-beta1/Smad
      signalling in renal mesangial cells.
AB  - The critical involvement of TGF-beta1 (transforming growth factor-beta1) in DN
      (diabetic nephropathy) is well established. However, the role of CTGF (connective
      tissue growth factor) in regulating the complex interplay of TGF-beta1 signalling
      networks is poorly understood. The purpose of the present study was to
      investigate co-operative signalling between CTGF and TGF-beta1 and its
      physiological significance. CTGF was determined to bind directly to the TbetaRIII
      (TGF-beta type III receptor) and antagonize TGF-beta1-induced Smad
      phosphorylation and transcriptional responses via its N-terminal half.
      Furthermore, TGF-beta1 binding to its receptor was inhibited by CTGF. A
      consequent shift towards non-canonical TGF-beta1 signalling and expression of a
      unique profile of differentially regulated genes was observed in CTGF/TGF-beta1
      treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident
      in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels
      of CTGF. Knockdown of TbetaRIII restored TGF-beta1-mediated Smad signalling and
      cell contractility, suggesting that TbetaRIII is key for CTGF-mediated regulation
      of TGF-beta1. Comparison of gene expression profiles from CTGF/TGF-beta1-treated
      mesangial cells and human renal biopsy material with histological diagnosis of DN
      revealed significant correlation among gene clusters. In summary, mesangial cell
      responses to TGF-beta1 are regulated by cross-talk with CTGF, emphasizing the
      potential utility of targeting CTGF in DN.

PMID- 21871017
TI  - NFAT promotes carcinoma invasive migration through glypican-6.
AB  - Invasive migration of carcinoma cells is a prerequisite for the metastatic
      dissemination of solid tumours. Numerous mechanisms control the ability of cancer
      cells to acquire a motile and invasive phenotype, and subsequently degrade and
      invade the basement membrane. Several genes that are up-regulated in breast
      carcinoma are responsible for mediating the metastatic cascade. Recent studies
      have revealed that the NFAT (nuclear factor of activated T-cells) is a
      transcription factor that is highly expressed in aggressive breast cancer cells
      and tissues, and mediates invasion through transcriptional induction of pro
      invasion and migration genes. In the present paper we demonstrate that NFAT
      promotes breast carcinoma invasion through induction of GPC (glypican) 6, a cell
      surface glycoprotein. NFAT transcriptionally regulates GPC6 induction in breast
      cancer cells and binds to three regulatory elements in the GPC6 proximal
      promoter. Expression of GPC6 in response to NFAT signalling promotes invasive
      migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks
      this phenotype. The mechanism by which GPC6 promotes invasive migration involves
      inhibition of canonical beta-catenin and Wnt signalling, and up-regulation of non
      canonical Wnt5A signalling leading to the activation of JNK (c-Jun N-terminal
      kinase) and p38 MAPK (mitogen-activated protein kinase). Thus GPC6 is a novel
      NFAT target gene in breast cancer cells that promotes invasive migration through
      Wnt5A signalling.

PMID- 21871018
TI  - Non-bronchodilating mechanisms of tiotropium prevent airway hyperreactivity in a
      guinea-pig model of allergic asthma.
AB  - BACKGROUND AND PURPOSE: Asthma is characterized by reversible bronchoconstriction
      and airway hyperreactivity. Although M(3) muscarinic receptors mediate
      bronchoconstriction, non-selective muscarinic receptor antagonists are not
      currently recommended for chronic control of asthma. We tested whether selective
      blockade of M(3) receptors, at the time of antigen challenge, blocks subsequent
      development of airway hyperreactivity in antigen-challenged guinea-pigs.
      EXPERIMENTAL APPROACH: Ovalbumin-sensitized guinea-pigs were pretreated with 1
      ug.kg(-1) of a kinetically selective M(3) receptor antagonist, tiotropium, or 1
      mg.kg(-1) of a non-selective muscarinic receptor antagonist, atropine, and
      challenged with inhaled ovalbumin. Animals were anaesthetized, paralyzed,
      ventilated and vagotomized 24 h later. We measured vagally mediated
      bronchoconstriction and i.v. ACh-induced bronchoconstriction. KEY RESULTS:
      Electrical stimulation of both vagus nerves induced frequency-dependent
      bronchoconstriction in sensitized animals that was significantly increased after
      antigen challenge. Antigen-induced hyperreactivity was completely blocked by
      tiotropium pretreatment but only partially blocked by atropine pretreatment.
      Surprisingly, although tiotropium blocked bronchoconstriction induced by i.v.
      ACh, it did not inhibit vagally-induced bronchoconstriction in sensitized
      controls, suggesting that tiotropium does not block hyperreactivity by blocking
      receptors for vagally released ACh. Rather, tiotropium may have worked through an
      anti-inflammatory mechanism, since it inhibited eosinophil accumulation in the
      lungs and around nerves. CONCLUSIONS AND IMPLICATIONS: These data confirm that
      testing M(3) receptor blockade with exogenous ACh does not predict vagal
      blockade. Our data also suggest that selective blockade of M(3) receptors may be
      effective in asthma via mechanisms that are separate from inhibition of
      bronchoconstriction.

PMID- 21871019
TI  - Targeting a family B GPCR/RAMP receptor complex: CGRP receptor antagonists and
      migraine.
AB  - The clinical effectiveness of antagonizing the calcitonin gene-related peptide
      (CGRP) receptor for relief of migraine pain has been clearly demonstrated, but
      the road to the development of these small molecule antagonists has been
      daunting. The key hurdle that needed to be overcome was the CGRP receptor itself.
      The vast majority of the current antagonists recognize similar epitopes on the
      calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1
      (RAMP1). RAMP1 is a relatively small, single, transmembrane-spanning protein and
      along with the G-protein-coupled receptor CLR comprise a functional CGRP
      receptor. The tri-helical extracellular domain of RAMP1 plays a key role in the
      high affinity binding of CGRP receptor antagonists and drives their species
      selective pharmacology. Over the years, a significant amount of mutagenesis data
      has been generated to identify specific amino acids or regions within CLR and
      RAMP1 that are critical to antagonist binding and has directed attention to the
      CLR/RAMP1 extracellular domain (ECD) complex. Recently, the crystal structure of
      the CGRP receptor ECD has been elucidated and not only reinforces the early
      mutagenesis data, but provides critical insight into the molecular mechanism of
      CGRP receptor antagonism. This review will highlight the drug design hurdles that
      must be overcome to meet the desired potency, selectivity and pharmacokinetic
      profile while retaining drug-like properties. Although the development of these
      antagonists has proved challenging, blocking the CGRP receptor may one day
      represent a new way to manage migraine and offer hope to migraine sufferers.

PMID- 21871020
TI  - Protective role of uncoupling protein-2 against dextran sodium sulfate-induced
      colitis.
AB  - BACKGROUND AND AIMS: Uncoupling protein-2 (UCP-2) is a negative regulator of
      reactive oxygen species (ROS) production. We investigated the effect of UCP-2 on
      disease progression in a murine dextran sodium sulfate (DSS)-induced colitis
      model, and the expression and distribution of tight junction (TJ) proteins, such
      as occludin, zonula-1 (ZO-1), claudin-4, and junctional adhesion molecule-1 (JAM
      1). METHODS: Male UCP-2(-/-) mice and wild-type littermates were divided into
      four groups: groups I and II, which comprised each type of mouse, were
      administered 2.5% DSS dissolved in drinking water to create a colitis model. The
      control groups (groups III and IV, which comprised each type of mouse) were given
      normal drinking water. Disease progression was evaluated according to colon
      length and the disease activity index. The distribution of TJ proteins was
      detected by immunohistochemical analysis. RESULTS: Compared with wild-type
      littermates, UCP-2(-/-) mice treated with DSS developed more severe diarrhea,
      body weight loss (P < 0.01), significantly short colon length, and more
      inflammatory cell infiltration into the mucosa and submucosa. The level of
      malondialdehyde in colonic mucosa increased in UCP-2(-/-) mice treated with DSS
      compared with the wild-type littermates (P < 0.001). The distribution of the ZO-1
      and JAM-1 proteins was significantly decreased in the colonic mucosa of UCP-2(-/
      ) mice compared with the wild-type littermates, whereas occludin and claudin-4
      distribution were not different between the UCP-2(-/-) mice and wild-type
      littermates. CONCLUSIONS: UCP-2 might reduce intestinal inflammatory response
      through the negative regulation of ROS, and affects the expression and
      distribution of TJ proteins.

PMID- 21871021
TI  - Outcome of hepatitis C virus infection in Chinese paid plasma donors: a 12-19
      year cohort study.
AB  - BACKGROUND AND AIMS: Commercial plasma donation was introduced in China in the
      1970s. Cases of non-A, non-B hepatitis (hepatitis C) continued to occur, with
      multiple outbreaks among plasma donors in Guan county, Hebei province between
      1972 and 1990. The outcomes of hepatitis C virus (HCV) infection in these paid
      plasma donors from six villages of Guan county were followed up for 12-19 years.
      METHODS: A total of 402 plasma donors with HCV infection were enrolled since anti
      HCV-positive in 1991 or 1998. Follow up was maintained until death or the end of
      the observation period. No antiviral treatment was applied during the period of
      infection. RESULTS: Follow up was lost in 23 cases. After a 12-19-year follow up,
      31 donors died, with the cause of death directly related to liver disease in 15
      cases, and an overall mortality of 8.18% (31/379). The incidence of liver
      cirrhosis was 10.03%, and hepatocellular carcinoma (HCC) was 2.90%. The rate of
      viral spontaneous clearing was 20.32% (77/379), and 13.69% (23/168) in males and
      25.59% (54/211) in females. In May 2010, detections were performed in 348 cases.
      Abnormality of liver function was related to HCV viremia. Sex and alcohol intake
      impacted the outcome of HCV infection. There was no correlation between the viral
      spontaneous clearance with age of infection and genotype. CONCLUSIONS: This area
      has a high rate of chronicity in HCV infection due to plasma donation. Twenty
      five years after virus infection, liver cirrhosis or HCC developed in one-tenth
      of patients, with an overall mortality of 8.18%.

PMID- 21871022
TI  - Male sex, hiatus hernia, and Helicobacter pylori infection associated with
      asymptomatic erosive esophagitis.
AB  - BACKGROUND AND AIMS: Asymptomatic erosive esophagitis (AEE) is an easily
      forgotten subgroup of gastroesophageal reflux disease due to its lack of warning
      symptoms, despite having the risk of developing complications, such as bleeding,
      stricture, or even esophageal adenocarcinoma. METHODS: A total of 2843
      potentially eligible patients were screened at the health management center of
      Buddhist Tzu Chi General Hospital. A total of 1001 patients responded to the
      survey and gave informed consent; 998 patients who completed the reflux disease
      diagnostic questionnaire were enrolled. Of them, 594 patients who had no reflux
      symptoms were included for final analysis. The presence and severity of erosive
      esophagitis was graded according to the Los Angeles classification. Active
      infection of Helicobacter pylori (H. pylori) was determined by the Campylo-like
      organism (CLO) test during endoscopies. RESULTS: A total of 14.5% (86/594) of
      asymptomatic patients had endoscopic findings of erosive esophagitis. In the
      univariate analysis, male sex and hiatus hernia were significantly associated
      with AEE. Positive CLO tests had a trend association. Based on the multivariate
      analysis, male sex (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.35
      3.98), hiatus hernia (OR: 4.48, 95% CI: 2.35-89.17), and positive CLO test (OR:
      0.57, 95% CI: 0.34-0.95) were associated with AEE, as compared to the healthy
      controls. CONCLUSIONS: AEE is not a rare condition, and constitutes 14.5% of the
      asymptomatic population. Male sex, hiatus hernia, and H. pylori infection are
      factors associated with AEE. These findings are not only helpful in identifying
      such asymptomatic patients, but also provide information to improve understanding
      of the relationship between H. pylori infection, reflux symptoms, and erosive
      esophagitis.

PMID- 21871023
TI  - Ribavirin downmodulates inducible costimulator on CD4+ T cells and their
      interleukin-10 secretion to assist in hepatitis C virus clearance.
AB  - BACKGROUND AND AIM: The immunological mechanism by which ribavirin (RBV)
      polarizes the T-helper (Th) 1/2 balance toward Th1 predominancy is not fully
      understood. We therefore examined whether RBV affects costimulatory signaling,
      which is known to be essential for regulating the Th1/2 balance. METHODS: The
      expression of costimulatory molecules and their ligands, and levels of various
      cytokines, released from CD4(+) T cells obtained from healthy individuals or
      patients with chronic hepatitis C virus (HCV) infection were analyzed. RESULTS:
      In CD4(+) T cells, RBV selectively downmodulates the expression of inducible
      costimulator (ICOS), a ligand for B7-H2 on dendritic cells, which mainly
      differentiates Th0 into Th2 cells. Moreover, the levels of interleukin-10 (IL-10)
      released from RBV-stimulated CD4(+) T cells also decreased, indicating that the
      downmodulation of ICOS induced by RBV might be correlated with the decrease in IL
      10 released from Th cells, leading to the inhibition of Th2 activity. An analysis
      of the association between ICOS kinetics and hepatitis C virus (HCV) elimination
      in hepatitis C patients receiving combined pegylated interferon and RBV indicated
      that HCV elimination tended to occur more frequently in patients showing ICOS
      downmodulation with RBV treatment. A decrease in IL-10 production by CD4(+) T
      cells was also observed in association with ICOS downregulation in patients who
      succeeded in HCV elimination. CONCLUSIONS: The downmodulation of ICOS in
      correlation with a reduction in IL-10 produced by CD4(+) T cells is possibly the
      immunological mechanism of action of RBV, which polarizes the Th1/2 balance
      toward a Th1 cytokine profile, thus contributing to the elimination of cells
      chronically infected with HCV.

PMID- 21871024
TI  - Current status on the diagnosis and management of pancreatic cysts in the Asia
      Pacific region: role of endoscopic ultrasound.
AB  - Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play
      increasingly prominent roles in the diagnosis and management of pancreatic cysts.
      The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct
      collaborative research in this area. This is a review of literature on true
      pancreatic cysts. Due to the lack of systematic studies, there are no robust data
      on the true incidence of pancreatic cystic lesions in Asia and any change in over
      the recent decades. Certain EUS morphological features have been used to predict
      particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology,
      pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen,
      can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the
      most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can
      either be observed or resected depending on the benign or malignant nature, or
      malignant potential of the lesions. Guidelines from an international consensus
      did not require positive cytological findings to be present in their
      recommendation for resection, which included all mucinous cystic neoplasms, all
      main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN,
      symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients
      with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts
      is an alternative. As long-term prospective data on pancreatic cysts are still
      not available in Asia, management strategies are largely based on risk
      stratification by surgical risk and malignant potential. Gene expression
      profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination
      of pancreatic cysts are novel techniques currently being studied.

PMID- 21871025
TI  - Sequential therapy achieves a higher eradication rate than standard triple
      therapy in Taiwan.
AB  - BACKGROUND AND AIMS: Most clinical trials concerning sequential therapy have been
      conducted in Italy. The efficacy of sequential therapy for Helicobacter pylori
      (H. pylori) eradication in Asia remains unclear. The aim of this study was to
      compare the efficacy of sequential therapy with standard triple therapy in
      Taiwan. METHODS: From January 2005 to December 2009, 233 H. pylori-infected
      patients receiving either a 10-day sequential therapy (40 mg pantoprazole and 1 g
      amoxicillin, twice daily, for the initial 5 days, followed by 40 mg pantoprazole,
      500 mg clarithromycin, and 500 mg metronidazole, twice daily, for the subsequent
      5 days, n = 118) or a 7-day standard triple therapy (40 mg pantoprazole, 500 mg
      clarithromycin, and 1 g amoxicillin twice daily for 7 days, n = 115) were
      included in the retrospective study. All the patients underwent a follow-up
      endoscopy with a rapid urease test and histological examination or a urea breath
      test at 8 weeks after the end of anti-H. pylori therapy to assess H. pylori
      status. RESULT: Intention-to-treat analysis demonstrated a significantly higher
      eradication rate for the sequential group than for the triple group (93% vs 80%,
      respectively, P = 0.003). Per-protocol analysis also showed similar results (93%
      vs 80%, P = 0.005). Both groups had similar frequencies of adverse events (29% vs
      22%) and drug compliance (98% vs 97%). CONCLUSION: Sequential therapy achieves a
      higher eradication rate than standard triple therapy in Taiwan. The novel
      treatment can be used as a first-line therapy for H. pylori infection for
      Taiwanese.

PMID- 21871026
TI  - Perioperative reactivation of hepatitis B virus replication in patients
      undergoing partial hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Reactivation of hepatitis B virus (HBV) replication happens
      in patients who receive transarterial chemoembolization or systemic chemotherapy
      for hepatocellular carcinoma (HCC). The incidence and risk factors of HBV
      reactivation during the perioperative period in HCC patients receiving hepatic
      resection is unknown. METHODS: Between May 2009 and November 2010, 164
      consecutive patients with HBV-related HCC who underwent hepatic resection were
      prospectively enrolled in the study. Among these, 126 patients received antiviral
      treatment before the operation (the antiviral group) and 38 patients did not
      receive any antiviral treatment (the non-antiviral group). RESULTS: Ten patients
      (6.1%) developed HBV reactivation perioperatively (within 1 month after
      hepatectomy). The incidence of HBV reactivation in the antiviral group and non
      antiviral group were 1.6% (2/126) and 21.1% (8/38), respectively (P < 0.001). On
      univariate analysis, preoperative HBV DNA < 1.0 * 10(3) copies/mL and non
      antiviral therapy were significantly correlated with the occurrence of HBV
      reactivation (P = 0.044 and P < 0.001, respectively). Only non-antiviral therapy
      remained as a predictive factor on multivariate analysis (odds ratio, 15.46; 95%
      confidence interval, 2.80-85.46, P = 0.002). The recovery of liver function
      (defined as a decrease of alanine aminotransferase back to normal) was achieved
      in 86.8% (132/152) patients without HBV reactivation and in 37.5% (3/8) patients
      with HBV reactivation when evaluated on day 30 after hepatectomy (P < 0.001).
      CONCLUSION: Hepatectomy could reactivate HBV replication during the perioperative
      period, especially in patients who did not receive any antiviral therapy. A close
      monitoring of HBV DNA during the perioperative period was necessary irrespective
      of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy
      should be given.

PMID- 21871027
TI  - Is transient elastography valuable for high-risk esophageal varices prediction in
      patients with hepatitis-B-related cirrhosis?
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the clinical value of
      transient elastography (TE) for high-risk esophageal varices (HREV) prediction in
      hepatitis-B-related cirrhosis patients. METHODS: A total of 238 patients with
      hepatitis B cirrhosis were prospectively enrolled. All patients had undergone TE
      and upper gastrointestinal endoscopy. Diagnostic value was assessed by the area
      under ROC curve (AUROC), predictive value and likelihood ratio. RESULTS: The size
      of esophageal varices correlated with liver stiffness with Kendall's tau_b 0.236
      overall and 0.425 in patients with ALT >= 5 * upper limit of normal (ULN). The
      AUROC of TE predicting HREV was 0.73 (95% confidence interval 0.66-0.80) overall
      and 0.92 (0.82-1.01) for patients with ALT >= 5 * ULN. In patients with ALT >= 5
      * ULN, cut-off 36.1 kPa predicted HREV with a 100% negative predictive value
      (NPV), an indefinite negative likelihood ratio (NLR), a 72.7% positive predictive
      value (PPV) and a positive likelihood ratio (PLR) of 9.3. The AUROC of HREV
      predicting model, constructed by ultrasonography and TE (USLS), was 0.84 (0.77
      0.90) in the training set and 0.85 (0.76-0.94) in the validating set. Cut-off
      3.30 excluded HREV with NPV 0.946 and NLR 0.10, and cut-off 5.98 determined HREV
      with PPV 0.870 and PLR 10.24. Using USLS, nearly 50% of patients could avoid
      endoscopic screening. The model's predictive values were maintained at similar
      accuracy in the validation set. Differences of AUROC in USLS, liver
      stiffness/spleen diameter to platelet ratio score and ultrasonic score were not
      significant. CONCLUSIONS: TE may predict HREV in patients with ALT >= 5 * ULN.
      Overall, the clinical values of TE and USLS for HREV prediction should be
      evaluated by further studies.

PMID- 21871028
TI  - A multispecies framework for landscape conservation planning.
AB  - Rapidly changing landscapes have spurred the need for quantitative methods for
      conservation assessment and planning that encompass large spatial extents. We
      devised and tested a multispecies framework for conservation planning to
      complement single-species assessments and ecosystem-level approaches. Our
      framework consisted of 4 elements: sampling to effectively estimate population
      parameters, measuring how human activity affects landscapes at multiple scales,
      analyzing the relation between landscape characteristics and individual species
      occurrences, and evaluating and comparing the responses of multiple species to
      landscape modification. We applied the approach to a community of terrestrial
      birds across 25,000 km(2) with a range of intensities of human development. Human
      modification of land cover, road density, and other elements of the landscape,
      measured at multiple spatial extents, had large effects on occupancy of the 67
      species studied. Forest composition within 1 km of points had a strong effect on
      occupancy of many species and a range of negative, intermediate, and positive
      associations. Road density within 1 km of points, percent evergreen forest within
      300 m, and distance from patch edge were also strongly associated with occupancy
      for many species. We used the occupancy results to group species into 11 guilds
      that shared patterns of association with landscape characteristics. Our
      multispecies approach to conservation planning allowed us to quantify the trade
      offs of different scenarios of land-cover change in terms of species occupancy.

PMID- 21871029
TI  - Introduction: The prospects for public health reform.

PMID- 21871030
TI  - Improving the population's health: the Affordable Care Act and the importance of
      integration.
AB  - Despite evidence indicating that public health services are the most effective
      means of improving the population's health status, health care services receive
      the bulk of funding and political support. The recent passage of the Affordable
      Care Act, which focused on improving access to health care services through
      insurance reform, reflects the primacy of health care over public health.
      Although policymakers typically conceptualize health care and public health as
      two distinct systems, gains in health status are most effectively and cost
      efficiently achieved through their integration into a single health system. The
      Act does little to compel integration; however, there are numerous opportunities
      to encourage the coordination of public health and health care in the Act's
      implementation.

PMID- 21871031
TI  - From health care reform to public health reform.
AB  - Even when turning its attention to public health topics such as preventive care
      and workplace wellness, the Affordable Care Act law embodies a highly
      individualistic paradigm of health. The provisions of the law implicitly assign
      the primary responsibility for prevention to individuals, who should be urged to
      make more responsible and healthier choices about what they consume and how they
      live. Relatively little in the law reflects the "population perspective" set
      forth in public health scholarship that focuses on environmental and social
      determinants of health. This article explores the cultural and economic factors
      that led Congress to embrace a highly individualist conception of public health,
      and it suggests how public health advocates and legal scholars might seek to
      reframe the public discourse surrounding preventive health issues.

PMID- 21871032
TI  - The Patient Protection and Affordable Care Act, public health, and the elusive
      target of human rights.
AB  - The Patient Protection and Affordable Care Act (ACA) sets in motion a wide range
      of programs that substantially affected the health system in the United States
      and signify a moderate but important regulatory shift in the role of the federal
      government in public health. This article briefly addresses two interesting
      policy paradoxes about the ACA. First, while the legislation primarily addresses
      health care financing and insurance and establishes only a few initiatives
      directly targeting public health, the ACA nevertheless has the potential to
      produce extensive public health benefits across the United States population by
      improving access to health care and services and reducing cost. Essentially, the
      ACA does not take the explicit form of a public health law but instead strives to
      advance public health indirectly through its effects. Second, while the ACA does
      not establish a right to health - or even a right to health insurance - in the
      United States, it does set in motion a number of significant structural and
      normative changes to United States law that comport with the attainment of the
      right to health. Most significantly, key provisions of the bill are designed to
      improve availability, accessibility, acceptability, and quality of conditions
      necessary for health, and to prompt the government to respect, protect, and
      fulfill these conditions. These developments mean that, to a degree, the United
      States essentially has undertaken the same types of legal and policy steps that a
      country would be required to take to uphold the right to health without actually
      recognizing the right to health in any formal or legally binding way. Despite
      these dual paradoxes and the upside potential for public health improvements
      resulting from the ACA, the public health impact of the law remains uncertain and
      will be decided by numerous subsequent regulatory and implementation decisions.
      The ACA authorizes multiple federal agencies to engage in rulemaking, a process
      that will largely dictate the systemic and health impacts that will become its
      legacy. This reality opens up ample opportunity to bolster public health aspects
      and interpretations of the law, and to simultaneously augment the corresponding
      components of the right to health.

PMID- 21871033
TI  - The Affordable Care Act's preventive services mandate: breaking down the barriers
      to nationwide access to preventive services.
AB  - The Affordable Care Act (ACA) transforms the U.S.'s public and private health
      care financing systems into vehicles for promoting public health by making
      evidence-based preventive services available nationwide through individual and
      group health plans, Medicare, and Medicaid. The ACA accomplishes this
      transformation by breaking down two barriers: (1) the public health-health care
      divide, which led to a dominance of curative medicine over preventive health
      measures and (2) ERISA preemption, which created an obstacle to the provision of
      a uniform set of evidence-based preventive services that could be made available
      to the U.S. population through individual and group health plans. As a result,
      prevention measures with proven effectiveness will now be provided on a national
      and uniform basis to a majority of Americans, with the potential to improve
      health outcomes and reduce costs.

PMID- 21871034
TI  - PPACA and public health: creating a framework to focus on prevention and wellness
      and improve the public's health.
AB  - PPACA epitomizes comprehensive health care reform legislation. Public health,
      disease prevention, and wellness were integral considerations in its development.
      This article reveals the author's personal experiences while working on the
      framework for health care reform in the United States Senate and reviews activity
      in the United States House of Representatives. This insider's perspective
      delineates PPACA's positive effect on public health by examining the
      infrastructure Congress designed to focus on prevention, wellness, and public
      health, with a particular focus on the National Prevention, Health Promotion and
      Public Health Council; the National Prevention, Health Promotion, Public Health,
      and Integrative Health Care Strategy; and the Prevention and Public Health Fund.
      The Council, strategy, and fund are especially important because they reflect
      compliance with some of the Institute of Medicine's recommendations to improve
      public health in the United States, as well as international health and human
      rights norms that protect the right to health.

PMID- 21871035
TI  - Obesity and health system reform: private vs. public responsibility.
AB  - Obesity is a particularly vexing public health challenge, since it not only
      underlies much disease and health spending but also largely stems from repeated
      personal behavioral choices. The newly enacted comprehensive health reform law
      contains a number of provisions to address obesity. For example, insurance
      companies are required to provide coverage for preventive-health services, which
      include obesity screening and nutritional counseling. In addition, employers will
      soon be able to offer premium discounts to workers who participate in wellness
      programs that emphasize behavioral choices. These policies presume that
      government intervention to reduce obesity is necessary and justified. Some
      people, however, argue that individuals have a compelling interest to pursue
      their own health and happiness as they see fit, and therefore any government
      intervention in these areas is an unwarranted intrusion into privacy and one's
      freedom to eat, drink, and exercise as much or as little as one wants. This paper
      clarifies the overlapping individual, employer, and social interest in each
      person's health generally to avoid obesity and its myriad costs in particular.
      The paper also explores recent evidence on the impact of government interventions
      on obesity through case studies on food labeling and employer-based anti-obesity
      interventions. Our analysis suggests a positive role for government intervention
      to reduce and prevent obesity. At the same time, we discuss criteria that can be
      used to draw lines between government, employer, and individual responsibility
      for health, and to derive principles that should guide and limit government
      interventions on obesity as health reform's various elements (e.g., exchanges,
      insurance market reforms) are implemented in the coming years.

PMID- 21871036
TI  - Combating obesity through the built environment: is there a clear path to
      success?
AB  - This article focuses on how an often-overlooked portion of PPACA, "Community
      Transformation Grants," might close the evidence gap in the relationship between
      obesity and the built environment and provide a pathway to effectively address
      this medically and economically costly epidemic.

PMID- 21871037
TI  - Congress, courts, and commerce: upholding the individual mandate to protect the
      public's health.
AB  - Among multiple legal challenges to the Patient Protection and Affordable Care Act
      (PPACA) is the premise that PPACA's "individual mandate" (requiring all
      individuals to obtain health insurance by 2014 or face civil penalties) is
      inviolate of Congress' interstate commerce powers because Congress lacks the
      power to regulate commercial "inactivity." Several courts initially considering
      this argument have rejected it, but federal district courts in Virginia and
      Florida have concurred, leading to numerous appeals and prospective review of the
      United States Supreme Court. Despite creative arguments, the dispositive
      constitutional question is not whether Congress' interstate commerce power
      extends to commercial inactivity. Rather, it is whether Congress may regulate
      individual decisions with significant economic ramifications in the interests of
      protecting and promoting the public's health. This article offers a counter
      interpretation of the scope of Congress' interstate commerce power to regulate in
      furtherance of the public's health.

PMID- 21871038
TI  - The individual mandate: implications for public health law.
AB  - No provision of the Patient Protection and Affordable Care Act (PPACA) has been
      more contentious than the so-called "individual mandate," the constitutionality
      of which is now before several appellate courts. Critics claim that the mandate
      represents an unprecedented attempt by the federal government to compel
      individual action. Yet, states frequently employ similar mandates to protect the
      public's health. These public health mandates have also often aroused deep
      opposition. This essay situates PPACA's mandate, and the opposition to it, in
      that broader context. The article reviews the arguments that public health's
      population perspective provides in support of mandates, as well as the reasons
      why mandates often ignite intense legal and political opposition. Most
      importantly, by holding individuals accountable for population-based problems,
      mandates may undercut the public health arguments that justify them. The article
      concludes by arguing that public health policymakers need to know more about the
      unintended political and legal costs of mandates.

PMID- 21871039
TI  - Conscripted physician services and the public's health.
AB  - The prevailing wisdom is that improving patient access to physician services is
      essential to promoting the public's health. This article suggests that,
      ironically, one effect of the 2010 federal health reform legislation may be to
      discourage physicians from serving the statute's intended beneficiaries, thereby
      exacerbating the access problem. The article examines several potential
      approaches to addressing this problem, comparing - from legal and policy
      perspectives - strategies based on legal conscription of physician services
      versus strategies that instead would rely on incentivizing physician
      participation in serving otherwise access-impaired populations. The author argues
      in favor of the latter approach rather than one based on use of governmental
      force.

PMID- 21871040
TI  - Improving health care outcomes through personalized comparisons of treatment
      effectiveness based on electronic health records.
AB  - Comparative effectiveness research (CER) is one of the Patient Protection and
      Affordable Care Act's significant initiatives that aims to improve treatment
      outcomes and lower health care costs. This article takes CER a step further and
      suggests a novel clinical application for it. The article proposes the
      development of a national framework to enable physicians to rapidly perform,
      through a computerized service, medically sound personalized comparisons of the
      effectiveness of possible treatments for patients' conditions. A treatment
      comparison for a given patient would be based on data from electronic health
      records of a cohort of clinically similar patients who received the treatments
      previously and whose outcomes were recorded. This framework has unique potential
      to simultaneously improve the quality of health care, reduce its cost, and
      alleviate public concerns about rationing and "one size fits all" medicine.

PMID- 21871041
TI  - The new era of comparative effectiveness: will public health end up left behind?
AB  - The Patient Protection and Affordable Care Act created the nation's first
      comprehensive comparative effectiveness research (CER) program. According to some
      optimistic accounts, CER will revolutionize clinical practice and transform the
      health care delivery system. But what about public health? There are reasons for
      concern that it could end up left behind in the new era of comparative
      effectiveness. This article analyzes the considerable promise and serious
      limitations of applying CER to public health. It also highlights important issues
      that will likely emerge for public health law and policy as the health care
      system transitions to greater reliance on CER.

PMID- 21871042
TI  - The law, policy, and ethics of employers' use of financial incentives to improve
      health.
AB  - The Patient Protection and Affordable Care Act (ACA) turns to a nontraditional
      mechanism to improve public health: employer-provided financial incentives for
      healthy behaviors. Critics raise questions about incentive programs'
      effectiveness, employer involvement, and potential discrimination. We support
      incentive program development despite these concerns. The ACA sets the stage for
      a broad-based research and implementation agenda through which we can learn to
      structure incentive programs to not only promote public health but also address
      prevalent concerns.

PMID- 21871043
TI  - When public health and genetic privacy collide: positive and normative theories
      explaining how ACA's expansion of corporate wellness programs conflicts with
      GINA's privacy rules.
AB  - The Patient Protection and Affordable Care Act of 2010 (ACA) contains many
      provisions intended to increase access to and lower the cost of health care by
      adopting public health measures. One of these promotes the use of at-work
      wellness programs by both providing employers with grants to develop these
      programs and also increasing their ability to tie the price employees pay for
      health insurance for participating in these programs and meeting specific health
      goals. Yet despite ACA's specific alteration of three different statues which had
      in the past shielded employees from having to contribute to the cost of their
      health insurance based on their achieving employer-designated health markers, it
      chose to leave alone recently enacted rules implementing the Genetic Non
      Discrimination Act (GINA), which prohibits employers from asking employees about
      their family health history in any context, including assessing their risk for
      setting wellness targets. This article reviews how both the changes made by ACA
      and the restrictions recently put place by GINA will affect the way employers are
      likely to structure Wellness Programs. It also considers how these changes
      reflect the competing social goals of both ACA, which seeks to expand access to
      the population by lowering costs, and GINA, which seeks to protect individuals
      from discrimination. It does so by analyzing both positive theories about how
      these new laws will function and normative theories explaining the likelihood of
      future friction between the interests of the population of the United States as a
      whole who are in need of increased and affordable access to health care, and of
      the individuals living in this country who risk discrimination, as science and
      medicine continue to make advances in linking genetic make-up to risk of future
      illness.

PMID- 21871044
TI  - Justice, fairness, and membership in a class: conceptual confusions and moral
      puzzles in the regulation of human subjects research.
AB  - This essay examines conceptual difficulties with one of the ways in which justice
      has been understood and applied the ethical and regulatory review of human
      research. Justice requires the fair distribution of the benefits and burdens of
      research. Class membership is seen as justifying inclusion in higher hazard-no
      benefit research from which members of potentially vulnerable classes, such as
      children, typically would be excluded. I argue that class membership does not do
      the justificatory work it is thought to do and that the use of class membership
      to justify inclusion in higher hazard-no benefit research leads to unjustified
      discrimination of sick children and offers special protections to healthy
      children.

PMID- 21871045
TI  - Inclusion of racial and ethnic minorities in genetic research: advance the spirit
      by changing the rules?
AB  - Genetic research aimed at understanding human health and disease is grounded in
      the study of genetic variation. The inclusion of research subjects with diverse
      ancestral backgrounds is essential for genetic and genomic research that fully
      explores human diversity. Large-scale cohort studies and biobanks in Europe and
      the United States often do not include the breadth of ethnic and racial diversity
      observed in their countries' citizens. This article explores the findings of a
      qualitative study of U.S. scientists' understanding and views of the NIH Policy
      and Guidelines on the Inclusion of Minorities as Subjects in Clinical Research.
      The findings suggest that the policy restricts how scientists use racial and
      ethnic categories to define and report their study populations and does little to
      motivate their efforts to increase the inclusion of non-European ancestral
      populations in genetic and genomic research.

PMID- 21871046
TI  - Views and experiences of IRBs concerning research integrity.
AB  - Institutional Review Boards (IRBs) can play vital roles in observing, monitoring,
      and responding to research integrity (RI) issues among researchers, yet many
      questions remain concerning whether, when, and in what ways these boards adopt
      these roles. I contacted 60 IRBs (every fourth one in the list of the top 240
      institutions by NIH funding), and interviewed leaders from 34 (response
      rate=55%), and an additional 12 members and administrators. IRBs become involved
      in a variety of RI problems, broadly defined, and face challenges in deciding how
      and when to do so. IRBs vary in how they define, discover, and respond to RI
      problems, and interact with other institutional offices concerning these issues;
      and what types of RI violations they encountered. While many institutions
      establish separate Compliance Offices, the boundaries and relationships between
      these entities and IRBs vary; and many IRBs discover and monitor RI violations,
      and struggle with how to respond. Larger questions arise of how IRBs decide
      whether to trust vs. closely monitor individual PIs. IRBs' roles are often
      indirect, and not fully systematic, raising questions of whether these functions
      should be enhanced, and if so, to what degree, and how. These areas require
      heightened investigation and discussion.

PMID- 21871047
TI  - Minimal risk in research involving pregnant women and fetuses.
AB  - The concept of minimal risk plays a key role in federal regulations on the
      protection of human research subjects. Although there has been considerable
      discussion of the meaning of minimal risk, the question of how this concept
      should be interpreted in research involving pregnant women and fetuses has not
      been addressed. This essay reviews the literature on minimal risk and argues for
      an interpretation of that concept in the context of research involving pregnant
      women and fetuses.

PMID- 21871048
TI  - Improve medical malpractice law by letting health care insurers take charge.
AB  - This essay discusses unlimited insurance subrogation (UIS) as a means of
      improving the deterrence and compensation results of medical malpractice law.
      Under UIS, health care insureds could assign their entire potential medical
      malpractice claims to their first-party commercial and government insurers. UIS
      should improve deterrence by establishing first-party insurers as plaintiffs to
      confront liability insurers on the defense side, leading to more effective
      prosecution of meritorious claims and reducing meritless and unnecessary
      litigation. UIS should improve compensation outcomes by converting litigation
      cost- and risk- laden "tort insurance" into cheaper and enhanced first-party
      insurance. UIS also promises dynamic benefits through further reforms by contract
      between the first-party and liability insurers that would take charge of system.
      No UIS-related costs are apparent that would outweigh these benefits.

PMID- 21871049
TI  - Paying human subjects in research: where are we, how did we get here, and now
      what?
AB  - Both international and federal regulations exist to ensure that scientists
      perform research on human subjects in an environment free of coercion and in
      which the benefits of the research are commensurate with the risks involved.
      Ensuring that these conditions hold is difficult, and perhaps even more so when
      protocols include the issue of monetary compensation of research subjects. The
      morality of paying human research subjects has been hotly debated for over 40
      years, and the grounds for this debate have ranged from discussion of legal
      rights, economic rights, philosophical principles of vulnerability and altruism
      to bioethical concepts of consent, best-interest determination, and justice
      theory. However, the thought surrounding these issues has evolved over time, and
      the way we think about the role of the human research subject today is markedly
      different than the way we thought in the past. Society first thought of the
      research subject as an altruist, necessarily giving of his time to benefit
      society as a whole. As time progressed, many suggested that the subject should
      not need to sacrifice himself for research: if something goes wrong, someone
      should compensate the subject for injuries. The concept of redress evolved into a
      system in which subjects were offered money as an inducement to participate in
      research, sometimes merely to offset the monetary costs of participation, but
      sometimes even to mitigate the risks of the study. This article examines ethical
      and legal conversations regarding compensation from the 1960s through today,
      examining theories of the ethics of compensation both comparatively and
      critically. In conclusion, we put forward an ethical framework for treating paid
      research subjects, with an attempt to use this framework as a means of resolving
      some of the more difficult problems with paying human subjects in research.

PMID- 21871050
TI  - Currents in contemporary bioethics: waiving informed consent to prenatal
      screening and diagnosis? Problems with paradoxical negotiation in surrogacy
      contracts.

PMID- 21871051
TI  - How to develop a simulation programme in urology.
AB  - What's known on the subject? and What does the study add? Inanimate trainers and
      simulators have been shown to facilitate the skill acquisition of urologists.
      However, there are significant challenges to integrating standalone simulation
      programmes into mainstream urology curricula. This study provides a framework to
      overcome these challenges and discusses the advantages of centralised urology
      simulation centres and their potential to serve as key adjuncts in the
      certification and validation process of urologists. Fixed performance-based
      outcomes of inanimate trainers and simulators have been praised as useful
      adjuncts in urology for reducing the learning curve associated with the
      acquisition of new technical and non-technical skills without compromising
      patient safety. Simulators are becoming an integral part of the urology training
      curriculum and their effectiveness is totally dependent on the structure of the
      programme implemented. The present paper discusses the fundamental concepts of
      centralized urology centres and their potential to serve as key adjuncts in the
      certification and validation process of urologists. In summary, proficiency-based
      curricula with well structured endpoints and objective tools for validating
      proficiency are critical in developing a simulation programme in urology. We
      concludes that more educational research into the outcomes of integrated urology
      curricula followed by trainee/trainer opinion surveys will help address some of
      these criteria.

PMID- 21871052
TI  - Safer urethral catheters: how study of catheter balloon pressure and force can
      guide design.
AB  - OBJECTIVES: To better define urethral catheter balloon pressures and extraction
      forces during traumatic placement and removal of urethral catheters. To help
      guide design for safer urethral catheters. MATERIALS AND METHODS: Measurements of
      balloon pressure were made upon filling within the urethra vs the bladder.
      Extraction forces were measured upon removal of a catheter with a filled balloon
      from the bladder. Models for the bladder and urethra included an ex vivo model
      (funnel, 'bladder', attached to a 30 F tube, 'urethra') and fresh human male
      cadavers. The mean (SEM) balloon pressures and extraction forces were calculated.
      RESULTS: In the ex vivo model, the mean (SEM) pressures upon filling the balloon
      with 10 mL were on average three-times higher within the ex vivo'urethra' (177
      [6] kPa) vs 'bladder' (59 [2] kPa) across multiple catheter types. In the human
      cadaver, the mean balloon pressure was 1.9-times higher within the urethra (139
      [11] kPa) vs bladder (68 [4] kPa). Balloon pressure increased non-linearly during
      intraurethral filling of both models, resulting in either balloon rupture
      (silicone catheters) or 'ballooning' of the neck of the balloon filling port
      (latex catheters). Removal of a filled balloon per the ex vivo model 'urethra'
      and cadaveric urethra, similarly required increasing force with greater balloon
      fill volumes (e.g. 9.34 [0.44] N for 5 mL vs 41.37 [8.01] N for 10 mL balloon
      volume). CONCLUSIONS: Iatrogenic complications from improper urethral catheter
      use is common. Catheter balloon pressures and manual extraction forces associated
      with urethral injury are significantly greater than those found with normal use.
      The differences in pressure and force may be incorporated into a safer urethral
      catheter design, which may significantly reduce iatrogenic urethral injury
      associated with catheterization.

PMID- 21871053
TI  - Prognostic factors in a large multi-institutional series of papillary renal cell
      carcinoma.
AB  - OBJECTIVES: To investigate cancer-related outcomes and prognostic factors of
      papillary renal cell carcinoma (pRCC) in a large multicentre data set.
      Oncological outcome and prognostic factors of pRCC have been limitedly evaluated
      in comparison with the most common RCC subtype, clear cell RCC. PATIENTS AND
      METHODS: From a multicentre retrospective database, including 5463 patients who
      were surgically treated for RCC at 16 Italian academic centres between 1995 and
      2007, 577 patients with pRCC were identified. Univariable and multivariable Cox
      regression models were performed to identify prognostic factors predictive of
      recurrence-free survival (RFS) and cancer-specific survival (CSS) after surgery.
      RESULTS: At a median (interquartile range) follow-up of 39.2 (21.7-72) months, 81
      (14%) patients had experienced disease progression and 63 (11%) patients had died
      from disease; the 5-year RFS estimate was 85.5%. In multivariable analysis,
      pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007)
      and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of
      RFS; the 5-year CSS estimate was 87.9%. In Cox multivariable analysis, an
      independent predictive role was reconfirmed for mode of presentation (pooled P=
      0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P=
      0.049) and Fuhrman nuclear grade (pooled P= 0.037). CONCLUSIONS: Patients with
      pRCC have a low risk of tumour recurrence and cancer-related death after surgery.
      Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS,
      whereas only a non-statistically significant trend was found for the 2009
      pathological T stage.

PMID- 21871054
TI  - Does the transrectal ultrasound probe influence prostate cancer detection in
      patients undergoing an extended prostate biopsy scheme? Results of a large
      retrospective study.
AB  - OBJECTIVE: * To compare the prostate cancer detection rate and tolerance profile
      between a transrectal biopsy made with a 'side fire' (SF) and an 'end fire' (EF)
      ultrasound probe. PATIENTS AND METHODS: * We selected patients undergoing first
      biopsy and re-biopsy of the prostate with a 14- and 18-core template using EF and
      SF transrectal probes, respectively. * We compared the cancer detection rate
      between the two probes on first biopsy and re-biopsy and gauged patient tolerance
      using a visual analogue scale (VAS). RESULTS: * A total of 1705 patients were
      included in the first biopsy group, while 487 were in the re-biopsy group. * The
      overall detection rate of first biopsy was 37.2%; the overall detection rate of
      re-biopsy was 10.1%. * No significant difference was found between the two probes
      in the first biopsy and re-biopsy sets (38% vs 36.5%, P= 0.55; 10.8% vs 9.3%, P=
      0.7). * The lack of any significant association between the type of probe used
      and prostate cancer detection was confirmed by univariable and multivariable
      analyses in both the first biopsy and re-biopsy sets after accounting for
      prostate-specific antigen values, per cent free prostate-specific antigen,
      digital rectal examination, and prostate and transition zone volumes. * The
      patient tolerance profile of the SF group was significantly better than that of
      the EF group (mean VAS 1.78 +/- 2.01 vs 1.45 +/- 2.21; P= 0.02). CONCLUSION: *
      The prostate cancer detection rate does not depend on the type of probe used.
      However, the SF transrectal probe is associated with a better patient tolerance
      profile.

PMID- 21871055
TI  - Therapeutic options to prevent recurrence of an aggressive aneurysmatic bone cyst
      of the cervical spine of a 16 year old boy - a case report.
AB  - The aneurysmatic bone cyst (ABC) is a benign primary bone tumour. If located in
      the cervical spine, its expansive growth and destructive behaviour may lead to
      instability and serious neurological impairment. We report a case of a 16-year
      old boy with an aggressive ABC in the 7th cervical vertebra. Computertomographic
      and magnetic resonance imaging revealed the envelopment of the left 7th and 8th
      spinal nerve along with the anterior displacement of the left vertebral artery.
      The interdisciplinary surgical strategy consisted of a partially incomplete cyst
      resection, subtotal spondylectomy with posterior screw-and-rod fixation from C6
      Th1, iliac crest bone grafting and anterior plating from C6-Th1. With regard to
      the high rate of recurrence after incomplete resection published in the recent
      literature, the patient was postoperatively treated by megavoltage radiotherapy
      with a total dose of 30Gy (daily dose of 1.8 Gy for 3 weeks). The clinical and
      radiographic follow-up showed complete recovery of all neurologic impairments and
      no signs of tumour recurrence at 3, 6 and 12 months after surgery. This case
      highlights diverse treatment regimens and shall outline the challenge and the
      problems of the interdisciplinary decision-making in adolescents presenting with
      ABC in high-demanding anatomical regions.

PMID- 21871056
TI  - sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive
      insulin therapy.
AB  - INTRODUCTION: Hyperglycemia represents an independent prognostic factor in
      critically ill non-diabetic patients but not in those with diabetes. In this
      context, there is an ongoing debate on the benefit of an intensive insulin
      therapy, particularly in diabetic patients. We tested the hypothesis that
      expression of the receptor for advanced glycation end-products (RAGE), an
      important signal transduction receptor that elicits long-lasting nuclear factor
      kappa B (NF-kappaB) activation, may underlie this difference. RAGE expression is
      regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and
      is reflected by its released soluble form (sRAGE). METHODS: A predesigned
      analysis was conducted of prospectively collected samples from 76 hyperglycemic
      critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged >= 18 years
      with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial
      comparing intensive insulin therapy with conventional insulin therapy. sRAGE and
      its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of
      inflammation and endothelial cell injury, respectively) were evaluated in ICU, at
      Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as
      controls. RESULTS: Both diabetic and non-diabetic hyperglycemic patients showed
      increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of
      admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic
      patients. Plasma levels of sRAGE were higher in diabetic compared with non
      diabetic patients. Intensive insulin therapy resulted in a significant decrease
      of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic
      patients. Circulating sRAGE levels correlated positively with IL-6 and soluble
      thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis
      demonstrated that sRAGE remains independently correlated with HMGB-1 only in
      diabetic patients. Neither sRAGE nor any inflammatory markers are associated with
      mortality. CONCLUSIONS: These findings support the hypothesis that sRAGE release,
      time-course and response to intensive insulin therapy differ between
      hyperglycemic diabetic and non-diabetic critically ill patients. Whether this
      difference underlies the dissimilarity in clinical outcome of hyperglycemia in
      these two conditions warrants further studies.

PMID- 21871057
TI  - Walnut oil increases cholesterol efflux through inhibition of stearoyl CoA
      desaturase 1 in THP-1 macrophage-derived foam cells.
AB  - BACKGROUND: Walnuts significantly decrease total and low-density lipoprotein
      cholesterol in normo- and hypercholesterolemic individuals. No study to date has
      evaluated the effects of walnuts on cholesterol efflux, the initial step in
      reverse cholesterol transport, in macrophage-derived foam cells (MDFC). The
      present study was conducted to investigate the mechanisms by which walnut oil
      affects cholesterol efflux. METHODS: The extract of English walnuts (walnut oil)
      was dissolved in DMSO and applied to cultured THP-1 MDFC cells (0.5 mg/mL). THP-1
      MDFC also were treated with human sera (10%, v:v) taken from subjects in a walnut
      feeding study. Cholesterol efflux was examined by liquid scintillation counting.
      Changes in gene expression were quantified by real time PCR. RESULTS: Walnut oil
      treatment significantly increased cholesterol efflux through decreasing the
      expression of the lipogenic enzyme stearoyl CoA desaturase 1 (SCD1) in MDFC.
      Alpha-linolenic acid (ALA), the major n-3 polyunsaturated fatty acids found in
      walnuts, recaptured SCD1 reduction in MDFC, a mechanism mediated through
      activation of nuclear receptor farnesoid-X-receptor (FXR). Postprandial serum
      treatment also increased cholesterol efflux in MDFC. When categorized by baseline
      C-reactive protein (CRP; cut point of 2 mg/L), subjects in the lower CRP sub
      group benefited more from dietary intervention, including a more increase in
      cholesterol efflux, a greater reduction in SCD1, and a blunted postprandial
      lipemia. CONCLUSION: In conclusion, walnut oil contains bioactive molecules that
      significantly improve cholesterol efflux in MDFC. However, the beneficial effects
      of walnut intake may be reduced by the presence of a pro-inflammatory state.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00938340.

PMID- 21871058
TI  - Citramalic acid and salicylic acid in sugar beet root exudates solubilize soil
      phosphorus.
AB  - BACKGROUND: In soils with a low phosphorus (P) supply, sugar beet is known to
      intake more P than other species such as maize, wheat, or groundnut. We
      hypothesized that organic compounds exuded by sugar beet roots solubilize soil P
      and that this exudation is stimulated by P starvation. RESULTS: Root exudates
      were collected from plants grown in hydroponics under low- and high-P
      availability. Exudate components were separated by HPLC, ionized by electrospray,
      and detected by mass spectrometry in the range of mass-to-charge ratio (m/z) from
      100 to 1000. Eight mass spectrometric signals were enhanced at least 5-fold by
      low P availability at all harvest times. Among these signals, negative ions with
      an m/z of 137 and 147 were shown to originate from salicylic acid and citramalic
      acid. The ability of both compounds to mobilize soil P was demonstrated by
      incubation of pure substances with Oxisol soil fertilized with calcium phosphate.
      CONCLUSIONS: Root exudates of sugar beet contain salicylic acid and citramalic
      acid, the latter of which has rarely been detected in plants so far. Both
      metabolites solubilize soil P and their exudation by roots is stimulated by P
      deficiency. These results provide the first assignment of a biological function
      to citramalic acid of plant origin.

PMID- 21871059
TI  - An increased risk of urinary tract infection precedes development of primary
      biliary cirrhosis.
AB  - BACKGROUND: Primary Biliary Cirrhosis is known to be associated with Urinary
      Tract Infections (UTIs), but whether these precede or follow the liver disease is
      unclear. We have therefore attempted to determine whether UTIs are more common in
      people with Primary Biliary Cirrhosis (PBC) prior to their diagnosis. METHODS: We
      conducted a case control study in the General Practice Research Database. All
      cases of PBC first recorded at least one year after entry to the dataset were
      selected along with up to 10 controls matched for age, sex. A second unmatched
      control group who had Chronic Liver Diseases but not PBC were chosen. The main
      exposures studied were the occurrence of Urinary tract infections and
      pyelonephritis at least one or at least five years before diagnosis. We also
      performed an analysis restricted to those younger than 55 at diagnosis, as we
      hypothesized the relationship to be stronger in the younger age group. RESULTS:
      PBC is associated with UTI prior to diagnosis, OR 1.50 (CI 1.26-1.78), which was
      similar 5 years prior to diagnosis and after adjusting for smoking. The strongest
      relationships were observed in pyelonephritis exposures five years before
      diagnosis in cases under 55 years: adjusted odds ratios were 2.60 (1.02-6.63) in
      comparison with matched general population controls and adjusted odds ratios were
      OR 2.45 (1.02-5.59) in the comparison with chronic liver disease controls.
      CONCLUSIONS: We found that the association between urosepsis and PBC is specific
      to this disease and precedes the diagnosis of PBC in a manner not previously
      observed in human data. This is consistent with a causal relationship.

PMID- 21871060
TI  - Evaluation of effectiveness of instruction and study habits in two consecutive
      clinical semesters of the medical curriculum Munich (MeCuM) reveals the need for
      more time for self study and higher frequency of assessment.
AB  - BACKGROUND: Seven years after implementing a new curriculum an evaluation was
      performed to explore possibilities for improvements. PURPOSES: To analyze
      students' study habits in relation to exam frequency and to evaluate
      effectiveness of instruction. METHODS: Time spent on self study (TSS) and the
      quantity of instruction (QI) was assessed during the internal medicine and the
      surgical semester. Students and faculty members were asked about study habits and
      their evaluation of the current curriculum. RESULTS: The TSS/QI ratio as a
      measure of effectiveness of instruction ranges mainly below 1.0 and rises only
      prior to exams. Students and teachers prefer to have multiple smaller exams over
      the course of the semester. Furthermore, students wish to have more time for self
      guided study. CONCLUSIONS: The TSS/QI ratio is predominantly below the aspired
      value of 1.0. Furthermore, the TSS/QI ratio is positively related to test
      frequency. We therefore propose a reduction of compulsory lessons and an increase
      in test frequency.

PMID- 21871061
TI  - Gene- or region-based association study via kernel principal component analysis.
AB  - BACKGROUND: In genetic association study, especially in GWAS, gene- or region
      based methods have been more popular to detect the association between multiple
      SNPs and diseases (or traits). Kernel principal component analysis combined with
      logistic regression test (KPCA-LRT) has been successfully used in classifying
      gene expression data. Nevertheless, the purpose of association study is to detect
      the correlation between genetic variations and disease rather than to classify
      the sample, and the genomic data is categorical rather than numerical. Recently,
      although the kernel-based logistic regression model in association study has been
      proposed by projecting the nonlinear original SNPs data into a linear feature
      space, it is still impacted by multicolinearity between the projections, which
      may lead to loss of power. We, therefore, proposed a KPCA-LRT model to avoid the
      multicolinearity. RESULTS: Simulation results showed that KPCA-LRT was always
      more powerful than principal component analysis combined with logistic regression
      test (PCA-LRT) at different sample sizes, different significant levels and
      different relative risks, especially at the genewide level (1E-5) and lower
      relative risks (RR = 1.2, 1.3). Application to the four gene regions of
      rheumatoid arthritis (RA) data from Genetic Analysis Workshop16 (GAW16) indicated
      that KPCA-LRT had better performance than single-locus test and PCA-LRT.
      CONCLUSIONS: KPCA-LRT is a valid and powerful gene- or region-based method for
      the analysis of GWAS data set, especially under lower relative risks and lower
      significant levels.

PMID- 21871062
TI  - Impact of education and training on type of care provided by community-based
      breastfeeding counselors: a cross-sectional study.
AB  - BACKGROUND: Studies using community-based breastfeeding counselors (CBBCs) have
      repeatedly shown positive impact on breastfeeding initiation, exclusivity and
      duration, particularly among low-income mothers. To date, there has not been a
      comprehensive study to determine the impact of CBBC attributes such as
      educational background and training, on the type of care that CBBCs provide.
      METHODS: This was a cross-sectional study of a convenience sample of CBBCs to
      ascertain the influence of counselor education and type of training on type of
      support and proficiency of CBBCs in communities across the United States.
      Invitations to participate in this online survey of CBBCs were e-mailed to
      program coordinators of the Special Supplemental Nutrition Program for Women,
      Infants, and Children (WIC), La Leche League, and other community-based health
      organizations, who in turn invited and encouraged their CBBCs to participate.
      Descriptive analysis was used to describe participants (N = 847), while bivariate
      analysis using chi2 test was used to examine the differences between CBBC
      education, training received and breastfeeding support skills used. Multivariate
      logistic regression was used to assess the independent determinants of specific
      breastfeeding support skills. RESULTS: The major findings from the research
      indicate that overall, educational attainment of CBBCs is not a significant
      predictor for the curriculum used in their training and type of support skills
      used during counseling sessions, but initial training duration was positively
      associated with the use of many breastfeeding support skills. Another major
      influence of counselor support to clients is the type of continuing education
      they receive after their initial training, with higher likelihood of use of
      desirable support skills associated with counselors continuing their
      breastfeeding education at conferences or trainings away from their job sites.
      CONCLUSIONS: Our results show that different programs use different training
      curricula to train their CBBCs varying in duration and content. Counselor
      education is not a significant predictor of the type of training they receive.
      Continuing breastfeeding education is a significant determinant of type of
      counseling techniques used with clients. Further research is therefore needed to
      critically examine the content of the various training curricula of CBBC
      programs. This may show a need for a standardized training curriculum for all
      CBBC programs worldwide to make CBBCs more proficient and efficient, ensuring
      successful and optimum breastfeeding experiences for mothers and their newborns.

PMID- 21871064
TI  - Patient and clinician's ratings of improvement in methadone-maintained patients:
      Differing perspectives?
AB  - BACKGROUND: In the last few years there seems to be an emerging interest for
      including the patients' perspective in assessing methadone maintenance treatment
      (MMT), with treatment satisfaction surveys being the most commonly-used method of
      incorporating this point of view. The present study considers the perspective of
      patients on MMT when assessing the outcomes of this treatment, acknowledging the
      validity of this approach as an indicator. The primary aim of this study is to
      evaluate the concordance between improvement assessment performed by two members
      of the clinical staff (a psychiatrist and a nurse) and assessment carried out by
      MMT patients themselves. METHOD: Patients (n = 110) and their respective
      psychiatrist (n = 5) and nurse (n = 1) completed a scale for assessing how the
      patient's condition had changed from the beginning of MMT, using the Patient
      Global Impression of Improvement scale (PGI-I) and the Clinical Global Impression
      of Improvement scale (CGI-I), respectively. RESULTS: The global improvement
      assessed by patients showed weak concordance with the assessments made by nurses
      (Quadratic-weighted kappa = 0.13, p > 0.05) and by psychiatrists (Quadratic
      weighted kappa = 0.19, p = 0.0086), although in the latter, concordance was
      statistically significant. The percentage of improved patients was significantly
      higher in the case of the assessments made by patients, compared with those made
      by nurses (90.9% vs. 80%, Z-statistic = 2.10, p = 0.0354) and by psychiatrists
      (90.9% vs. 50%, Z-statistic = 6.48, p < 0.0001). CONCLUSIONS: MMT patients'
      perception of improvement shows low concordance with the clinical staff's
      perspective. Assessment of MMT effectiveness should also focus on patient's
      evaluation of the outcomes or changes achieved, thus including indicators based
      on the patient's experiences, provided that MMT aim is to be more patient centred
      and to cover different needs of patients themselves.

PMID- 21871063
TI  - Review of juxtaglomerular cell tumor with focus on pathobiological aspect.
AB  - Juxtaglomerular cell tumor (JGCT) generally affects adolescents and young adults.
      The patients experience symptoms related to hypertension and hypokalemia due to
      renin-secretion by the tumor. Grossly, the tumor is well circumscribed with
      fibrous capsule and the cut surface shows yellow or gray-tan color with frequent
      hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells
      with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a
      positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic
      cells contain rhomboid-shaped renin protogranules. Genetically, losses of
      chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors
      showed a benign course, but rare tumors with vascular invasion or metastasis were
      reported. JGCT is a curable cause of hypertensive disease if it is discovered
      early and surgically removed, but may cause a fatal outcome usually by a
      cerebrovascular attack or may cause fetal demise in pregnancy. Additionally,
      pathologists and urologists need to recognize that this neoplasm in most cases
      pursues a benign course, but aggressive forms may develop in some cases.

PMID- 21871065
TI  - Developmental patterns and characteristics of epicardial cell markers Tbx18 and
      Wt1 in murine embryonic heart.
AB  - BACKGROUND: Although recent studies have highlighted the role of epicardial cells
      during cardiac development and regeneration, their cardiomyogenic potential is
      still controversial due to the question of lineage tracing of epicardial cells.
      The present study therefore aimed to examine the the expression of Tbx18 and Wt1
      in embryonic heart and to identify whether Tbx18 and Wt1 themselves expressed in
      the cardiomyocyte. METHODS: Mouse embryonic hearts were collected at different
      stages for immunofluorescence costaining with either Tbx18 and the cardiac
      transcription factor Nkx2.5 or Wilms tumor 1 (Wt1) and Nkx2.5. RESULTS: Tbx18 and
      Wt1, but not Nkx2.5, were expressed in the proepicardium and epicardium. Tbx18
      was expressed in cells within the heart from E10.5 to at least E14.5; these Tbx18
      expressing cells were Nkx2.5 positive, except for a few cells that were Nkx2.5
      negative at E14.5. Wt1 was expressed in cells within the heart from E12.5 to at
      least E14.5, but these Wt1-expressing cells were Nkx2.5 negative. CONCLUSION: The
      data obtained in this study demonstrate that Tbx18 is expressed in the
      cardiomyocytes from E10.5 to at least E14.5, and Wt1 is expressed within the
      heart from E12.5 to at least E14.5, but not in the cardiomyocyte. These findings
      may provide new insights on the role of the epicardial cells in cardiac
      regeneration.

PMID- 21871066
TI  - Tunisian Toxoplasma gondii strains genotyping by the use of AK69 marker.
AB  - BACKGROUND: Clinical manifestation due to infection by Toxoplasma gondii is
      closely linked to the infecting strain of the parasite. Several genetic markers
      are available to determinate its genotype but few of them are able to
      discriminate between the three predominant lineages, namely types I, II and III.
      The number of markers decreases when atypical, recombinant/mixed genotypes need
      to be identified. FINDINGS: In our study, the contribution of sequence
      polymorphisms in the AK69 gene as typing markers for T. gondii was investigated
      for the first time in an epidemiological study. The coding region of the marker
      was amplified, sequenced and aligned for different Toxoplasma strains. The
      identified nucleotide polymorphism at 12 positions was able to highly
      discriminate between the different congenital toxoplasmosis Tunisian strains.
      Moreover the high detection sensitivity level of the marker enabled unambiguous
      identification of mixed/recombinant genotypes directly. CONCLUSION: It can be,
      thus, very useful for direct typing in areas where such genotypes are frequently
      encountered, mainly in the African continent.

PMID- 21871067
TI  - Factors associated with shunt dynamic in patients with cryptogenic stroke and
      patent foramen ovale: an observational cohort study.
AB  - BACKGROUND: As previously reported there is evidence for a reduction in right to
      left shunt (RLS) in stroke patients with patent foramen ovale (PFO). This occurs
      predominantly in patients with cryptogenic stroke (CS). We therefore analysed
      factors associated with a shunt reduction on follow-up in stroke patients
      suffering of CS. METHODS: On index event PFO and RLS were proven by
      transesophageal echocardiography and contrast-enhanced transcranial Doppler
      sonography (ce-TCD). Silent PE was proved by ventilation perfusion scintigraphy
      (V/Q) within the stroke work-up on index event; all scans were re-evaluated in a
      blinded manner by two experts. The RLS was re-assessed on follow-up by ce-TCD. A
      reduction in shunt volume was defined as a difference of >=20 microembolic
      signals (MES) or the lack of evidence of RLS on follow-up. For subsequent
      analyses patients with CS were considered; parameters such as deep vein
      thrombosis (DVT) and silent pulmonary embolism (PE) were analysed. RESULTS: In 39
      PFO patients suffering of a CS the RLS was re-assessed on follow-up. In all
      patients (n = 39) with CS a V/Q was performed; the median age was 40 years, 24
      (61.5%) patients were female. In 27 patients a reduction in RLS was evident.
      Silent PE was evident in 18/39 patients (46.2%). Factors such as atrial septum
      aneurysm, DVT or even silent PE were not associated with RLS dynamics. A greater
      time delay from index event to follow-up assessment was associated with a
      decrease in shunt volume (median 12 vs. 6 months, p = 0.013). CONCLUSIONS: In
      patients with CS a reduction in RLS is not associated with the presence of a
      venous embolic event such as DVT or silent PE. A greater time delay between the
      initial and the follow-up investigation increases the likelihood for the
      detection of a reduction in RLS.

PMID- 21871068
TI  - A study of patient attitudes towards decentralisation of HIV care in an urban
      clinic in South Africa.
AB  - BACKGROUND: In South Africa, limited human resources are a major constraint to
      achieving universal antiretroviral therapy (ART) coverage. Many of the public
      sector HIV clinics operating within tertiary facilities, that were the first to
      provide ART in the country, have reached maximum patient capacity.
      Decentralization or "down-referral" (wherein ART patients deemed stable on
      therapy are referred to their closest Primary Health Clinics (PHCs) for treatment
      follow-up) is being used as a possible alternative of ART delivery care. This
      cross-sectional qualitative study investigates attitudes towards down-referral of
      ART delivery care among patients currently receiving care in a centralized
      tertiary HIV clinic. METHODS: Ten focus group discussions (FGDs) with 76
      participants were conducted in early 2008 amongst ART patients initiated and
      receiving care for more than 3 months in the tertiary HIV clinic study site.
      Eligible individuals were invited to participate in FGDs involving 6-9
      participants, and lasting approximately 1-2 hours. A trained moderator used a
      discussion topic guide to investigate the main issues of interest including:
      advantages and disadvantages of down-referral, potential motivating factors and
      challenges of down-referral, assistance needs from the transferring clinic as
      well as from PHCs. RESULTS: Advantages include closeness to patients' homes,
      transport and time savings. However, patients favour a centralized service for
      the following reasons: less stigma, patients established relationship with the
      centralized clinic, and availability of ancillary services. Most FGDs felt that
      for down-referral to occur there needed to be training of nurses in patient
      provider communication. CONCLUSION: Despite acknowledging the down-referral
      advantages of close proximity and lower transport costs, many participants
      expressed concerns about lack of trained HIV clinical staff, negative patient
      interactions with nurses, limited confidentiality and stigma. There was consensus
      that training of nurses and improved health systems at the local clinics were
      needed if successful down-referral was to take place.

PMID- 21871069
TI  - PTSD, depression and anxiety among former abductees in Northern Uganda.
AB  - BACKGROUND: The population in Northern Uganda has been exposed to extreme levels
      of traumatic stress and thousands abducted forcibly became rebel combatants.
      METHODS: Using structured interviews, the prevalence and severity of
      posttraumatic stress disorder (PTSD), depression and anxiety was assessed in 72
      former abducted adults, 62 of them being former child soldiers. RESULTS: As
      retrospective reports of exposure to traumatic stress increased, anxiety and PTSD
      occurrence increased (r = .45). 49% of respondents were diagnosed with PTSD, 70%
      presented with symptoms of depression, and 59% with those of anxiety. In a
      multiple linear regression analysis four factors could best explain the
      development of PTSD symptoms: male respondents (sex) living in an IDP-Camp
      (location) with a kinship murdered in the war (family members killed in the war)
      and having experienced a high number of traumatic events (number of traumatic
      events) were more likely to develop symptoms of PTSD than others. In disagreement
      to a simple dose-response-effect though, we also observed a negative correlation
      between the time spent with the rebels and the PTSD symptom level. CONCLUSIONS:
      Former abductees continue to suffer from severe mental ill-health. Adaptation to
      the living condition of rebels, however, may lower trauma-related mental
      suffering.

PMID- 21871070
TI  - Crystallization of Ti33Cu67 metallic glass under high-current density electrical
      pulses.
AB  - We have studied the phase and structure evolution of the Ti33Cu67 amorphous
      alloy subjected to electrical pulses of high current density. By varying the
      pulse parameters, different stages of crystallization could be observed in the
      samples. Partial polymorphic nanocrystallization resulting in the formation of 5-
      to 8-nm crystallites of the TiCu2 intermetallic in the residual amorphous matrix
      occurred when the maximum current density reached 9.7.108 A m-2 and the pulse
      duration was 140 MUs, though the calculated temperature increase due to Joule
      heating was not enough to reach the crystallization temperature of the alloy.
      Samples subjected to higher current densities and higher values of the evolved
      Joule heat per unit mass fully crystallized and contained the Ti2Cu3 and TiCu3
      phases. A common feature of the crystallized ribbons was their non-uniform
      microstructure with regions that experienced local melting and rapid
      solidification.PACS: 81; 81.05.Bx; 81.05.Kf.

PMID- 21871071
TI  - EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as
      tissue-specific methylation.
AB  - BACKGROUND: Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM,
      which can be discriminated by the chromosome 3 status or global mRNA expression
      profile. Metastatic progression is predominantly originated from class II tumors
      or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed
      detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM,
      cultured uveal melanocytes and normal tissues, to explore the role of the
      differentially methylated EFS promoter region CpG island in tumor classification
      and metastatic progression. METHODS: EFS methylation was determined by direct
      sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of
      individual cloned PCR products. The results were associated with clinical
      features of tumors and tumor-related death of patients. RESULTS: Analysis of 16
      UM showed full methylation of the EFS CpG island in 8 (50%), no methylation in 5
      (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a
      higher risk of metastatic progression for tumors with EFS methylation (p = 0.02).
      This correlation was confirmed in an independent set of 24 randomly chosen
      tumors. Notably, only UM with EFS methylation gave rise to metastases. Real-time
      quantitative RT-PCR expression analysis revealed a significant inverse
      correlation of EFS mRNA expression with EFS methylation in UM. We further found
      that EFS methylation is tissue-specific with full methylation in peripheral blood
      cells, and no methylation in sperm, cultured primary fibroblasts and fetal
      muscle, kidney and brain. Adult brain samples, cultured melanocytes from the
      uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial
      methylation. EFS methylation always affects both alleles in normal and tumor
      samples. CONCLUSIONS: Biallelic EFS methylation is likely to be the result of a
      site-directed methylation mechanism. Based on partial methylation as observed in
      cultured melanocytes we hypothesize that there might be methylated and
      unmethylated precursor cells located in the uveal tract. The EFS methylation of a
      UM may depend on which type of precursor cell the tumor originated from.

PMID- 21871073
TI  - An unusual case of suprascapular nerve neuropathy: a case report.
AB  - INTRODUCTION: Suprascapular nerve neuropathy constitutes an unusual cause of
      shoulder weakness, with the most common etiology being nerve compression from a
      ganglion cyst at the suprascapular or spinoglenoid notch. We present a puzzling
      case of a man with suprascapular nerve neuropathy that may have been associated
      with an appendectomy. The case was attributed to nerve injury as the most likely
      cause that may have occurred during improper post-operative patient mobilization.
      CASE PRESENTATION: A 23-year-old Caucasian man presented to an orthopedic surgeon
      with a history of left shoulder weakness of several weeks' duration. The patient
      complained of pain and inability to lift minimal weight, such as a glass of
      water, following an appendectomy. His orthopedic clinical examination revealed
      obvious atrophy of the supraspinatus and infraspinatus muscles and 2 of 5 muscle
      strength scores on flexion resistance and external rotation resistance. Magnetic
      resonance imaging showed diffuse high signal intensity within the supraspinatus
      and infraspinatus muscles and early signs of minimal fatty infiltration
      consistent with denervation changes. No compression of the suprascapular nerve in
      the suprascapular or spinoglenoid notch was noted. Electromyographic studies
      showed active denervation effects in the supraspinatus muscle and more prominent
      in the left infraspinatus muscle. The findings were compatible with damage to the
      suprascapular nerve, especially the part supplying the infraspinatus muscle. On
      the basis of the patient's history, clinical examination, and imaging studies,
      the diagnosis was suspected to be associated with a possible traction injury of
      the suprascapular nerve that could have occurred during the patient's transfer
      from the operating table following an appendectomy. CONCLUSION: Our case report
      may provide important insight into patient transfer techniques used by hospital
      personnel, may elucidate the clinical significance of careful movement of
      patients following general anesthesia, and may have important implications for
      patient safety techniques, including those outlined in the World Health
      Organization Surgical Safety Checklist program.

PMID- 21871072
TI  - A multicenter randomized controlled trial evaluating the effect of small stitches
      on the incidence of incisional hernia in midline incisions.
AB  - BACKGROUND: The median laparotomy is frequently used by abdominal surgeons to
      gain rapid and wide access to the abdominal cavity with minimal damage to nerves,
      vascular structures and muscles of the abdominal wall. However, incisional hernia
      remains the most common complication after median laparotomy, with reported
      incidences varying between 2-20%. Recent clinical and experimental data showed a
      continuous suture technique with many small tissue bites in the aponeurosis only,
      is possibly more effective in the prevention of incisional hernia when compared
      to the common used large bite technique or mass closure. METHODS/DESIGN: The
      STITCH trial is a double-blinded multicenter randomized controlled trial designed
      to compare a standardized large bite technique with a standardized small bites
      technique. The main objective is to compare both suture techniques for incidence
      of incisional hernia after one year. Secondary outcomes will include
      postoperative complications, direct costs, indirect costs and quality of life. A
      total of 576 patients will be randomized between a standardized small bites or
      large bites technique. At least 10 departments of general surgery and two
      departments of oncological gynaecology will participate in this trial. Both
      techniques have a standardized amount of stitches per cm wound length and suture
      length wound length ratio's are calculated in each patient. Follow up will be at
      1 month for wound infection and 1 year for incisional hernia. Ultrasound
      examinations will be performed at both time points to measure the distance
      between the rectus muscles (at 3 points) and to objectify presence or absence of
      incisional hernia. Patients, investigators and radiologists will be blinded
      during follow up, although the surgeon can not be blinded during the surgical
      procedure. CONCLUSION: The STITCH trial will provide level 1b evidence to support
      the preference for either a continuous suture technique with many small tissue
      bites in the aponeurosis only or for the commonly used large bites technique.

PMID- 21871074
TI  - HIV/AIDS, chronic diseases and globalisation.
AB  - HIV/AIDS has always been one of the most thoroughly global of diseases. In the
      era of widely available anti-retroviral therapy (ART), it is also commonly
      recognised as a chronic disease that can be successfully managed on a long-term
      basis. This article examines the chronic character of the HIV/AIDS pandemic and
      highlights some of the changes we might expect to see at the global level as HIV
      is increasingly normalised as "just another chronic disease". The article also
      addresses the use of this language of chronicity to interpret the HIV/AIDS
      pandemic and calls into question some of the consequences of an uncritical
      acceptance of concepts of chronicity.

PMID- 21871075
TI  - Psychopathological features of irritable bowel syndrome patients with and without
      functional dyspepsia: a cross sectional study.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) show
      considerable overlap and are both associated with psychiatric comorbidity. The
      present study aimed to investigate whether IBS patients with FD show higher
      levels of psychopathology than those without FD. As a preliminary analysis, it
      also evaluated the psychopathological differences, if any, between IBS patients
      featuring the two Rome III-defined FD subtypes, i.e. postprandial distress
      syndrome (PDS) and epigastric pain syndrome (EPS). METHODS: Consecutive
      outpatients (n = 82, F = 67, mean age 41.6 +/- 12.7 years) referred to our third
      level gastroenterological centre, matching the Rome III criteria for IBS and, if
      present, for concurrent FD, were recruited. They were asked to complete a 90-item
      self-rating questionnaire, the Symptom Checklist 90 Revised (SCL-90-R), in order
      to assess the psychological status. Comparisons between groups were carried out
      using the non-parametric Mann-Whitney U test. RESULTS: Patients with IBS only
      were 56 (68.3%, F = 43, mean age 41.6 +/- 13.3 years) and patients with both IBS
      and FD were 26 (31.7%, F = 24, mean age 41.8 +/- 11.5 years), 17 of whom had PDS
      and 9 EPS. Patients with both IBS and FD scored significantly higher on the SCL
      90-R GSI and on eight out of the nine subscales than patients with IBS only (P
      ranging from 0.000 to 0.03). No difference was found between IBS patients with
      PDS and IBS patients with EPS (P ranging from 0.07 to 0.97), but this result has
      to be considered provisional, given the small sample size of the two subgroups.
      CONCLUSIONS: IBS-FD overlap is associated with an increased severity of
      psychopathological features. This finding suggests that a substantial subset of
      patients of a third level gastroenterological centre with both IBS and FD may
      benefit from psychological assessment and treatment.

PMID- 21871076
TI  - Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and
      supplementation with docosahexaenoic acid--a case report.
AB  - This is a case report of adrenomyeloneuropathy (AMN), the adult variant of
      adrenoleukodystryphy (ALD). The diagnoses in the patient, aged 34, was confirmed
      via increased serum very long chain fatty acid concentration (VLCFA). Treatment
      started with the cholesterol lowering drug, atorvastatin, followed by add-on
      therapy with Lorenzo's oil (LO) and finally supplementation with docosahexaenoic
      acid (DHA). The magnetic resonance imaging (MRI) scan of the AMN patient before
      DHA treatment, already showed abnormal white matter in the brain. Although the
      MRI showed no neurological improvement after 6 months of DHA treatment, no
      selective progression of demyelination was detected in the AMN patient. Contrary
      to what was expected, LO failed to sustain or normalize the VLCFA levels or
      improve clinical symptoms. It was however, shown that DHA supplementation in
      addition to LO, increased DHA levels in both plasma and red blood cells (RBC).
      Additionally, the study showed evidence that the elongase activity in the
      elongation of eicosapentaenoic acid (EPA) to docosapentaenoic acid (DPA) might
      have been significantly compromised, due to the increased DHA levels.

PMID- 21871077
TI  - Analysis of high-identity segmental duplications in the grapevine genome.
AB  - BACKGROUND: Segmental duplications (SDs) are blocks of genomic sequence of 1-200
      kb that map to different loci in a genome and share a sequence identity > 90%.
      SDs show at the sequence level the same characteristics as other regions of the
      human genome: they contain both high-copy repeats and gene sequences. SDs play an
      important role in genome plasticity by creating new genes and modeling genome
      structure. Although data is plentiful for mammals, not much was known about the
      representation of SDs in plant genomes. In this regard, we performed a genome
      wide analysis of high-identity SDs on the sequenced grapevine (Vitis vinifera)
      genome (PN40024). RESULTS: We demonstrate that recent SDs (> 94% identity and >=
      10 kb in size) are a relevant component of the grapevine genome (85 Mb, 17% of
      the genome sequence). We detected mitochondrial and plastid DNA and genes (10% of
      gene annotation) in segmentally duplicated regions of the nuclear genome. In
      particular, the nine highest copy number genes have a copy in either or both
      organelle genomes. Further we showed that several duplicated genes take part in
      the biosynthesis of compounds involved in plant response to environmental stress.
      CONCLUSIONS: These data show the great influence of SDs and organelle DNA
      transfers in modeling the Vitis vinifera nuclear DNA structure as well as the
      impact of SDs in contributing to the adaptive capacity of grapevine and the
      nutritional content of grape products through genome variation. This study
      represents a step forward in the full characterization of duplicated genes
      important for grapevine cultural needs and human health.

PMID- 21871078
TI  - Helical tomotherapy in the treatment of pediatric malignancies: a preliminary
      report of feasibility and acute toxicity.
AB  - BACKGROUND: Radiation therapy plays a central role in the management of many
      childhood malignancies and Helical Tomotherapy (HT) provides potential to
      decrease toxicity by limiting the radiation dose to normal structures. The aim of
      this article was to report preliminary results of our clinical experience with HT
      in pediatric malignancies. METHODS: In this study 66 consecutive patients younger
      than 14 years old, treated with HT at our center between January 2006 and April
      2010, have been included. We performed statistical analyses to assess the
      relationship between acute toxicity, graded according to the RTOG criteria, and
      several clinical and treatment characteristics such as a dose and irradiation
      volume. RESULTS: The median age of patients was 5 years. The most common tumor
      sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most
      prevalent histological types were: medulloblastoma (16 patients), neuroblastoma
      (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were
      treated for primary disease and 14 patients were treated for recurrent tumors.
      The majority of the patients (72%) were previously treated with chemotherapy. The
      median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2
      acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological
      toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine
      patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade
      4 non-hematological toxicities. On the univariate analysis, total dose and
      craniospinal irradiation (24 cases) were significantly associated with severe
      toxicity (grade 3 or more), whereas age and chemotherapy were not. On the
      multivariate analysis, craniospinal irradiation was the only significant
      independent risk factor for grade 3-4 toxicity. CONCLUSION: HT in pediatric
      population is feasible and safe treatment modality. It is characterized by an
      acceptable level of acute toxicity that we have seen in this highly selected
      pediatric patient cohort with clinical features of poor prognosis and/or
      aggressive therapy needed. Despite of a dosimetrical advantage of HT technique,
      an exhaustive analysis of long-term follow-up data is needed to assess late
      toxicity, especially in this potentially sensitive to radiation population.

PMID- 21871079
TI  - On the dosimetric impact of inhomogeneity management in the Acuros XB algorithm
      for breast treatment.
AB  - BACKGROUND: A new algorithm for photon dose calculation, Acuros XB, has been
      recently introduced in the Eclipse, Varian treatment planning system, allowing,
      similarly to the classic Monte Carlo methods, for accurate modelling of dose
      deposition in media. Aim of the present study was the assessment of its behaviour
      in clinical cases. METHODS: Datasets from ten breast patients scanned under
      different breathing conditions (free breathing and deep inspiration) were used to
      calculate dose plans using the simple two tangential field setting, with Acuros
      XB (in its versions 10 and 11) and the Anisotropic Analytical Algorithm (AAA) for
      a 6MV beam. Acuros XB calculations were performed as dose-to-medium
      distributions. This feature was investigated to appraise the capability of the
      algorithm to distinguish between different elemental compositions in the human
      body: lobular vs. adipose tissue in the breast, lower (deep inspiration
      condition) vs. higher (free breathing condition) densities in the lung. RESULTS:
      The analysis of the two breast structures presenting densities compatible with
      muscle and with adipose tissue showed an average difference in dose calculation
      between Acuros XB and AAA of 1.6%, with AAA predicting higher dose than Acuros
      XB, for the muscle tissue (the lobular breast); while the difference for adipose
      tissue was negligible. From histograms of the dose difference plans between AAA
      and Acuros XB (version 10), the dose of the lung portion inside the tangential
      fields presented an average difference of 0.5% in the free breathing conditions,
      increasing to 1.5% for the deep inspiration cases, with AAA predicting higher
      doses than Acuros XB. In lung tissue significant differences are found also
      between Acuros XB version 10 and 11 for lower density lung. CONCLUSIONS: Acuros
      XB, differently from AAA, is capable to distinguish between the different
      elemental compositions of the body, and suggests the possibility to further
      improve the accuracy of the dose plans computed for actual treatment of patients.

PMID- 21871080
TI  - Predictors of adherence to a multifaceted podiatry intervention for the
      prevention of falls in older people.
AB  - BACKGROUND: Despite emerging evidence that foot problems and inappropriate
      footwear increase the risk of falls, there is little evidence as to whether foot
      related intervention strategies can be successfully implemented. The aim of this
      study was to evaluate adherence rates, barriers to adherence, and the predictors
      of adherence to a multifaceted podiatry intervention for the prevention of falls
      in older people. METHODS: The intervention group (n = 153, mean age 74.2 years)
      of a randomised trial that investigated the effectiveness of a multifaceted
      podiatry intervention to prevent falls was assessed for adherence to the three
      components of the intervention: (i) foot orthoses, (ii) footwear advice and
      footwear cost subsidy, and (iii) a home-based foot and ankle exercise program.
      Adherence to each component and the barriers to adherence were documented, and
      separate discriminant function analyses were undertaken to identify factors that
      were significantly and independently associated with adherence to the three
      intervention components. RESULTS: Adherence to the three components of the
      intervention was as follows: foot orthoses (69%), footwear (54%) and home-based
      exercise (72%). Discriminant function analyses identified that being younger was
      the best predictor of orthoses use, higher physical health status and lower fear
      of falling were independent predictors of footwear adherence, and higher physical
      health status was the best predictor of exercise adherence. The predictive
      accuracy of these models was only modest, with 62 to 71% of participants
      correctly classified. CONCLUSIONS: Adherence to a multifaceted podiatry
      intervention in this trial ranged from 54 to 72%. People with better physical
      health, less fear of falling and a younger age exhibited greater adherence,
      suggesting that strategies need to be developed to enhance adherence in frailer
      older people who are most at risk of falling. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry ACTRN12608000065392.

PMID- 21871081
TI  - Searching for early breast cancer biomarkers by serum protein profiling of pre
      diagnostic serum; a nested case-control study.
AB  - BACKGROUND: Serum protein profiles have been investigated frequently to discover
      early biomarkers for breast cancer. So far, these studies used biological samples
      collected at or after diagnosis. This may limit these studies' value in the
      search for cancer biomarkers because of the often advanced tumor stage, and
      consequently risk of reverse causality. We present for the first time pre
      diagnostic serum protein profiles in relation to breast cancer, using the
      Prospect-EPIC (European Prospective Investigation into Cancer and nutrition)
      cohort. METHODS: In a nested case-control design we compared 68 women diagnosed
      with breast cancer within three years after enrollment, with 68 matched controls
      for differences in serum protein profiles. All samples were analyzed with SELDI
      TOF MS (surface enhanced laser desorption/ionization time-of-flight mass
      spectrometry). In a subset of 20 case-control pairs, the serum proteome was
      identified and relatively quantified using isobaric Tags for Relative and
      Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid
      chromatography coupled with tandem MS (2D-nanoLC-MS/MS). RESULTS: Two SELDI-TOF
      MS peaks with m/z 3323 and 8939, which probably represent doubly charged
      apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), were higher in
      pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D
      nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin
      inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast
      cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p <
      0.05). C3a(desArg) and ITIH4 have previously been related to the presence of
      symptomatic and/or mammographically detectable breast cancer. CONCLUSIONS: We
      show that serum protein profiles are already altered up to three years before
      breast cancer detection.

PMID- 21871082
TI  - Automatic segmentation of meningioma from non-contrasted brain MRI integrating
      fuzzy clustering and region growing.
AB  - BACKGROUND: In recent years, magnetic resonance imaging (MRI) has become
      important in brain tumor diagnosis. Using this modality, physicians can locate
      specific pathologies by analyzing differences in tissue character presented in
      different types of MR images.This paper uses an algorithm integrating fuzzy-c
      mean (FCM) and region growing techniques for automated tumor image segmentation
      from patients with menigioma. Only non-contrasted T1 and T2 -weighted MR images
      are included in the analysis. The study's aims are to correctly locate tumors in
      the images, and to detect those situated in the midline position of the brain.
      METHODS: The study used non-contrasted T1- and T2-weighted MR images from 29
      patients with menigioma. After FCM clustering, 32 groups of images from each
      patient group were put through the region-growing procedure for pixels
      aggregation. Later, using knowledge-based information, the system selected tumor
      containing images from these groups and merged them into one tumor image. An
      alternative semi-supervised method was added at this stage for comparison with
      the automatic method. Finally, the tumor image was optimized by a morphology
      operator. Results from automatic segmentation were compared to the "ground truth"
      (GT) on a pixel level. Overall data were then evaluated using a quantified
      system. RESULTS: The quantified parameters, including the "percent match" (PM)
      and "correlation ratio" (CR), suggested a high match between GT and the present
      study's system, as well as a fair level of correspondence. The results were
      compatible with those from other related studies. The system successfully
      detected all of the tumors situated at the midline of brain.Six cases failed in
      the automatic group. One also failed in the semi-supervised alternative. The
      remaining five cases presented noticeable edema inside the brain. In the 23
      successful cases, the PM and CR values in the two groups were highly related.
      CONCLUSIONS: Results indicated that, even when using only two sets of non
      contrasted MR images, the system is a reliable and efficient method of brain
      tumor detection. With further development the system demonstrates high potential
      for practical clinical use.

PMID- 21871083
TI  - Using qualitative synthesis to explore heterogeneity of complex interventions.
AB  - BACKGROUND: Including qualitative evidence on patients' perspectives in
      systematic reviews of complex interventions may reveal reasons for variation in
      trial findings. This is particularly the case when the intervention is for a long
      term disease, as management may rely heavily on the efforts of the patient.
      Inclusion though seldom happens, possibly because of methodological challenges,
      and when it does occur the different forms of evidence are often kept separate.
      To explore heterogeneity in trial findings, we tested a novel approach to
      integrate qualitative review evidence on patients' perspectives with evidence
      from a Cochrane systematic review. METHODS: We used, as a framework for a matrix,
      evidence from a qualitative review on patients' perspectives on helping them
      manage their disease. We then logged in the matrix whether the interventions
      identified in a Cochrane review corresponded with the patient perspectives on how
      to help them. We then explored correspondence.The Cochrane review we used
      included 19 trials of interventions to improve adherence to therapy in HIV/AIDS
      patients. The qualitative review we used included 23 studies on HIV/AIDS
      patients' perspectives on adherence; it translated the themes identified across
      the studies into recommendations in how to help patients adhere.Both reviews
      assessed quality. In the qualitative review they found no difference in findings
      between the better quality studies and the weaker ones. In the Cochrane review
      they were unable to explore the impact of quality in subgroup analysis because so
      few studies were of good quality. RESULTS: Matrix tabulation of interventions and
      patients' perspectives identified a range of priorities raised by people infected
      with HIV-1 that were not addressed in evaluated interventions. Tabulation of the
      more robust trials revealed that interventions that significantly improved
      adherence contained more components considered important by patients than
      interventions where no statistically significant effect was found. CONCLUSIONS:
      This simple approach breaks new ground in cross tabulating qualitative evidence
      with the characteristics of trialled interventions. In doing so it tests the
      assumption that patients are more likely to adhere to interventions that match
      more closely with their concerns. The potential of this approach in exploring
      varying content and rates of success in trialled complex interventions deserves
      further evaluation.

PMID- 21871084
TI  - A whole blood monokine-based reporter assay provides a sensitive and robust
      measurement of the antigen-specific T cell response.
AB  - BACKGROUND: The ability to measure T-cell responses to antigens is proving
      critical in the field of vaccine development and for understanding immunity to
      pathogens, allergens and self-antigens. Although a variety of technologies exist
      for this purpose IFNgamma-ELISpot assays are widely used because of their
      sensitivity and simplicity. However, ELISpots cannot be performed on whole blood,
      and require relatively large volumes of blood to yield sufficient numbers of
      peripheral blood mononuclear cells. To address these deficiencies, we describe an
      assay that measures antigen-specific T cell responses through changes in monokine
      gene transcription. The biological amplification of the IFNgamma signal generated
      by this assay provides sensitivity comparable to ELISpot, but with the advantage
      that responses can be quantified using small volumes of whole blood. METHODS:
      Whole blood or peripheral blood mononuclear cells (PBMCs) from healthy controls
      and immunosuppressed recipients of solid organ transplants were incubated with
      peptide pools covering viral and control antigens or mitogen for 20 hours. Total
      RNA was extracted and reverse transcribed before amplification in a TaqMan qPCR
      reaction using primers and probes specific for MIG (CXCL9), IP-10 (CXCL10) and
      HPRT. The induction of MIG and IP-10 in response to stimuli was analysed and the
      results were compared with those obtained by ELISpot. RESULTS: Antigen-specific T
      cell responses can be measured through the induction of MIG or IP-10 gene
      expression in PBMCs or whole blood with results comparable to those achieved in
      ELISpot assays. The biological amplification generated by IFNgamma-R signaling
      allows responses to be detected in as little as 25 uL of whole blood and enables
      the assay to retain sensitivity despite storage of samples for up to 48 hours
      prior to processing. CONCLUSIONS: A monokine-based reporter assay provides a
      sensitive measure of antigen-specific T cell activation. Assays can be performed
      on small volumes of whole blood and remain accurate despite delays in processing.
      This assay may be a useful tool for studying T cell responses, particularly when
      samples are limited in quantity or when storage or transportation are required
      before processing.

PMID- 21871085
TI  - Ontology-based Brucella vaccine literature indexing and systematic analysis of
      gene-vaccine association network.
AB  - BACKGROUND: Vaccine literature indexing is poorly performed in PubMed due to
      limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine
      field. Vaccine Ontology (VO) is a community-based biomedical ontology that
      represents various vaccines and their relations. SciMiner is an in-house
      literature mining system that supports literature indexing and gene name tagging.
      We hypothesize that application of VO in SciMiner will aid vaccine literature
      indexing and mining of vaccine-gene interaction networks. As a test case, we have
      examined vaccines for Brucella, the causative agent of brucellosis in humans and
      animals. RESULTS: The VO-based SciMiner (VO-SciMiner) was developed to
      incorporate a total of 67 Brucella vaccine terms. A set of rules for term
      expansion of VO terms were learned from training data, consisting of 90
      biomedical articles related to Brucella vaccine terms. VO-SciMiner demonstrated
      high recall (91%) and precision (99%) from testing a separate set of 100 manually
      selected biomedical articles. VO-SciMiner indexing exhibited superior performance
      in retrieving Brucella vaccine-related papers over that obtained with MeSH-based
      PubMed literature search. For example, a VO-SciMiner search of "live attenuated
      Brucella vaccine" returned 922 hits as of April 20, 2011, while a PubMed search
      of the same query resulted in only 74 hits. Using the abstracts of 14,947
      Brucella-related papers, VO-SciMiner identified 140 Brucella genes associated
      with Brucella vaccines. These genes included known protective antigens, virulence
      factors, and genes closely related to Brucella vaccines. These VO-interacting
      Brucella genes were significantly over-represented in biological functional
      categories, including metabolite transport and metabolism, replication and
      repair, cell wall biogenesis, intracellular trafficking and secretion,
      posttranslational modification, and chaperones. Furthermore, a comprehensive
      interaction network of Brucella vaccines and genes were identified. The asserted
      and inferred VO hierarchies provide semantic support for inferring novel
      knowledge of association of vaccines and genes from the retrieved data. New
      hypotheses were generated based on this analysis approach. CONCLUSION: VO
      SciMiner can be used to improve the efficiency for PubMed searching in the
      vaccine domain.

PMID- 21871086
TI  - Admissions to intensive care unit of HIV-infected patients in the era of highly
      active antiretroviral therapy: etiology and prognostic factors.
AB  - INTRODUCTION: Although access to highly active antiretroviral therapy (HAART) has
      prolonged survival and improved life quality, HIV-infected patients with severe
      immunosuppression or comorbidities may develop complications that require
      critical care support in intensive care units (ICU). This study aimed to describe
      the etiology and analyze the prognostic factors of HIV-infected Taiwanese
      patients in the HAART era. METHODS: Medical records of all HIV-infected adults
      who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010
      were reviewed to record information on patient demographics, receipt of HAART,
      and reason for ICU admission. Factors associated with hospital mortality were
      analyzed. RESULTS: During the 10-year study period, there were 145 ICU admissions
      for 135 patients, with respiratory failure being the most common cause (44.4%),
      followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was
      not associated with survival. However, CD4 count was independently predictive of
      hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036;
      95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was
      independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to
      7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level
      (per 1-g/dl decrease) were associated with increased hospital mortality, but did
      not reach statistical significance in multivariable analysis. CONCLUSIONS:
      Respiratory failure was the leading cause of ICU admissions among HIV-infected
      patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and
      the diagnosis of sepsis, but was not associated with HAART in this study.

PMID- 21871087
TI  - Gender equality in couples and self-rated health - A survey study evaluating
      measurements of gender equality and its impact on health.
AB  - BACKGROUND: Men and women have different patterns of health. These differences
      between the sexes present a challenge to the field of public health. The question
      why women experience more health problems than men despite their longevity has
      been discussed extensively, with both social and biological theories being
      offered as plausible explanations. In this article, we focus on how gender
      equality in a partnership might be associated with the respondents' perceptions
      of health. METHODS: This study was a cross-sectional survey with 1400
      respondents. We measured gender equality using two different measures: 1) a self
      reported gender equality index, and 2) a self-perceived gender equality question.
      The aim of comparison of the self-reported gender equality index with the self
      perceived gender equality question was to reveal possible disagreements between
      the normative discourse on gender equality and daily practice in couple
      relationships. We then evaluated the association with health, measured as self
      rated health (SRH). With SRH dichotomized into 'good' and 'poor', logistic
      regression was used to assess factors associated with the outcome. For the
      comparison between the self-reported gender equality index and self-perceived
      gender equality, kappa statistics were used. RESULTS: Associations between gender
      equality and health found in this study vary with the type of gender equality
      measurement. Overall, we found little agreement between the self-reported gender
      equality index and self-perceived gender equality. Further, the patterns of
      agreement between self-perceived and self-reported gender equality were quite
      different for men and women: men perceived greater gender equality than they
      reported in the index, while women perceived less gender equality than they
      reported. The associations to health were depending on gender equality
      measurement used. CONCLUSIONS: Men and women perceive and report gender equality
      differently. This means that it is necessary not only to be conscious of the
      methods and measurements used to quantify men's and women's opinions of gender
      equality, but also to be aware of the implications for health outcomes.

PMID- 21871089
TI  - Massively multiplayer online role-playing games: comparing characteristics of
      addict vs non-addict online recruited gamers in a French adult population.
AB  - BACKGROUND: Massively Multiplayer Online Role-Playing Games (MMORPGs) are a very
      popular and enjoyable leisure activity, and there is a lack of international
      validated instruments to assess excessive gaming. With the growing number of
      gamers worldwide, adverse effects (isolation, hospitalizations, excessive use,
      etc.) are observed in a minority of gamers, which is a concern for society and
      for the scientific community. In the present study, we focused on screening
      gamers at potential risk of MMORPG addiction. METHODS: In this exploratory study,
      we focused on characteristics, online habits and problematic overuse in adult
      MMORPG gamers. In addition to socio-demographical data and gamer behavioral
      patterns, 3 different instruments for screening addiction were used in French
      MMORPG gamers recruited online over 10 consecutive months: the substance
      dependence criteria for the Diagnostic and Statistical Manual of Mental Disorder,
      fourth revised edition (DSM-IV-TR) that has been adapted for MMORPG (DAS), the
      qualitative Goldberg Internet Addiction Disorder scale (GIAD) and the
      quantitative Orman Internet Stress Scale (ISS). For all scales, a score above a
      specific threshold defined positivity. RESULTS: The 448 participating adult
      gamers were mainly young adult university graduates living alone in urban areas.
      Participants showed high rates of both Internet addiction (44.2% for GIAD, 32.6%
      for ISS) and DAS positivity (27.5%). Compared to the DAS negative group, DAS
      positive gamers reported significantly higher rates of tolerance phenomenon
      (increased amount of time in online gaming to obtain the desired effect) and
      declared significantly more social, financial (OR: 4.85), marital (OR: 4.61),
      family (OR: 4.69) and/or professional difficulties (OR: 4.42) since they started
      online gaming. Furthermore, these gamers self-reported significantly higher rates
      (3 times more) of irritability, daytime sleepiness, sleep deprivation due to
      play, low mood and emotional changes since online gaming onset. CONCLUSIONS: The
      DAS appeared to be a good first-line instrument to screen MMORPG addiction in
      online gamers. This study found high MMORPG addiction rates, and self-reported
      adverse symptoms in important aspects of life, including mood and sleep. This
      confirms the need to set up relevant prevention programs against online game
      overuse.

PMID- 21871088
TI  - Alzheimer's disease: synapses gone cold.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease
      characterized by insidious cognitive decline and memory dysfunction. Synapse loss
      is the best pathological correlate of cognitive decline in AD and mounting
      evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble
      oligomeric forms of amyloid beta (Abeta), the peptide that aggregates to form
      senile plaques in the brain of AD patients, have been shown to be toxic to
      neuronal synapses both in vitro and in vivo. Abeta oligomers inhibit long-term
      potentiation (LTP) and facilitate long-term depression (LTD),
      electrophysiological correlates of memory formation. Furthermore, oligomeric
      Abeta has also been shown to induce synapse loss and cognitive impairment in
      animals. The molecular underpinnings of these observations are now being
      elucidated, and may provide clear therapeutic targets for effectively treating
      the disease. Here, we review recent findings concerning AD pathogenesis with a
      particular focus on how Abeta impacts synapses.

PMID- 21871090
TI  - Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in
      Southern Spain along the decade 2000-2010.
AB  - BACKGROUND: Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan
      Africa and India although they have been found worldwide. In the last decade,
      immigration from these areas has increased considerably in Spain. The objective
      of this study was to evaluate the prevalence of non-B subtypes circulating in a
      cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify
      drug resistance-associated mutations. METHODS: Complete protease and first 220
      codons of the reverse transcriptase coding regions were amplified and sequenced
      by population sequencing. HIV-1 subtypes were determined using Stanford
      University Drug Resistance Database, and phylogenetic analysis was performed
      comparing multiple reported sequences. Drug resistance mutations were defined
      according to the International AIDS Society-USA. RESULTS: From 2000 to 2010 a
      total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our
      cohort. Of these, 121 were immigrants, of which 98 had ethical approval and
      informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%)
      were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly
      from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C,
      F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan
      Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01
      AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients
      infected with non-B subtypes showed a high frequency of minor protease inhibitor
      resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed
      major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and
      A98G were present in one patient with subtype G, L100I in one patient with
      CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other
      mutations such as V118I, E138A and V90I. CONCLUSIONS: The circulation of non-B
      subtypes has significantly increased in Southern Spain during the last decade,
      with 29.6% prevalence, in association with demographic changes among immigrants.
      This could be an issue in the treatment and management of these patients.
      Resistance mutations have been detected in these patients with a prevalence of 7%
      among treatment-naive patients compared with the 21% detected among patients
      under HAART or during treatment interruption.

PMID- 21871091
TI  - Role of IL-33 in inflammation and disease.
AB  - Interleukin (IL)-33 is a new member of the IL-1 superfamily of cytokines that is
      expressed by mainly stromal cells, such as epithelial and endothelial cells, and
      its expression is upregulated following pro-inflammatory stimulation. IL-33 can
      function both as a traditional cytokine and as a nuclear factor regulating gene
      transcription. It is thought to function as an 'alarmin' released following cell
      necrosis to alerting the immune system to tissue damage or stress. It mediates
      its biological effects via interaction with the receptors ST2 (IL-1RL1) and IL-1
      receptor accessory protein (IL-1RAcP), both of which are widely expressed,
      particularly by innate immune cells and T helper 2 (Th2) cells. IL-33 strongly
      induces Th2 cytokine production from these cells and can promote the pathogenesis
      of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis.
      However, IL-33 has shown various protective effects in cardiovascular diseases
      such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus,
      the effects of IL-33 are either pro- or anti-inflammatory depending on the
      disease and the model. In this review the role of IL-33 in the inflammation of
      several disease pathologies will be discussed, with particular emphasis on recent
      advances.

PMID- 21871092
TI  - Sustained favorable long-term outcome in the treatment of schizophrenia: a 3-year
      prospective observational study.
AB  - BACKGROUND: This study of chronically ill patients with schizophrenia aimed to
      identify patients who achieve sustained favorable long-term outcome - when the
      outcome incorporates severity of symptoms, level of functioning, and use of acute
      care services - and to identify the best baseline predictors of achieving this
      sustained favorable long-term outcome. METHODS: Using data from the United States
      Schizophrenia Care and Assessment Program (US-SCAP) (N = 2327), a large 3-year
      prospective, multisite, observational study of individuals treated for
      schizophrenia in the US, a hierarchical cluster analysis was performed to group
      patients based upon baseline symptom severity. Symptom severity was assessed
      using the Positive and Negative Syndrome Scale (PANSS) scores, level of
      functioning, and use of acute care services. Level of functioning reflected
      patient-reported productivity and clinician-rated occupational role functioning.
      Use of acute care services reflected self-reported psychiatric hospitalization
      and emergency service use. Change of health state was determined over the 3-year
      period. A patient was classified as having a sustained favorable long-term
      outcome if their health state values had the closest distance to the defined
      "best baseline cluster" at each point over the length of the study. Stepwise
      logistic regression was used to determine baseline predictors of sustained
      favorable long-term outcome. RESULTS: At baseline, 5 distinct health state
      clusters were identified, ranging from "best" to "worst." Of 1635 patients with
      sufficient data, only 157 (10%) experienced sustained favorable long-term outcome
      during the 2-years postbaseline. The baseline predictors associated with
      sustained favorable long-term outcome included better quality of life, more daily
      activities, patient-reported clearer thinking from medication, better global
      functioning, being employed, not being a victim of a crime, not having received
      individual therapy, and not having received help with shopping and leisure
      activities. CONCLUSIONS: Only a small percentage of patients achieved sustained
      favorable long-term outcome in this study, suggesting there continues to be a
      great need for improvement in the treatment of schizophrenia. Findings suggest
      that clinicians could make early projections of health states and identify those
      patients more likely to achieve favorable long-term outcomes enabling early
      therapeutic interventions to enhance benefits for patients.

PMID- 21871093
TI  - Rapid whole genome optical mapping of Plasmodium falciparum.
AB  - BACKGROUND: Immune evasion and drug resistance in malaria have been linked to
      chromosomal recombination and gene copy number variation (CNV). These events are
      ideally studied using comparative genomic analyses; however in malaria these
      analyses are not as common or thorough as in other infectious diseases, partly
      due to the difficulty in sequencing and assembling complete genome drafts.
      Recently, whole genome optical mapping has gained wide use in support of genomic
      sequence assembly and comparison. Here, a rapid technique for producing whole
      genome optical maps of Plasmodium falciparum is described and the results of
      mapping four genomes are presented. METHODS: Four laboratory strains of P.
      falciparum were analysed using the ArgusTM optical mapping system to produce
      ordered restriction fragment maps of all 14 chromosomes in each genome.
      Plasmodium falciparum DNA was isolated directly from blood culture, visualized
      using the ArgusTM system and assembled in a manner analogous to next generation
      sequence assembly into maps (AssemblyViewerTM, OpGen Inc.(r)). Full coverage maps
      were generated for P. falciparum strains 3D7, FVO, D6 and C235. A reference P.
      falciparum in silico map was created by the digestion of the genomic sequence of
      P. falciparum with the restriction enzyme AflII, for comparisons to genomic
      optical maps. Maps were then compared using the MapSolverTM software. RESULTS:
      Genomic variation was observed among the mapped strains, as well as between the
      map of the reference strain and the map derived from the putative sequence of
      that same strain. Duplications, deletions, insertions, inversions and
      misassemblies of sizes ranging from 3,500 base pairs up to 78,000 base pairs were
      observed. Many genomic events occurred in areas of known repetitive sequence or
      high copy number genes, including var gene clusters and rifin complexes.
      CONCLUSIONS: This technique for optical mapping of multiple malaria genomes
      allows for whole genome comparison of multiple strains and can assist in
      identifying genetic variation and sequence contig assembly. New protocols and
      technology allowed us to produce high quality contigs spanning four P. falciparum
      genomes in six weeks for less than $1,000.00 per genome. This relatively low cost
      and quick turnaround makes the technique valuable compared to other genomic
      sequencing technologies for studying genetic variation in malaria.

PMID- 21871094
TI  - High mobility group box protein 1 in complex with lipopolysaccharide or IL-1
      promotes an increased inflammatory phenotype in synovial fibroblasts.
AB  - INTRODUCTION: In addition to its direct proinflammatory activity, extracellular
      high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine
      response evoked by other proinflammatory molecules, such as lipopolysaccharide
      (LPS), CpG-DNA and IL-1beta, through the formation of complexes. Extracellular
      HMGB1 is abundant in arthritic joint tissue where it is suggested to promote
      inflammation as intra-articular injections of HMGB1 induce synovitis in mice and
      HMGB1 neutralizing therapy suppresses development of experimental arthritis. The
      aim of this study was to determine whether HMGB1 in complex with LPS, interleukin
      (IL)-1alpha or IL-1beta has enhancing effects on the production of
      proinflammatory mediators by rheumatoid arthritis synovial fibroblasts (RASF) and
      osteoarthritis synovial fibroblasts (OASF). Furthermore, we examined the toll
      like receptor (TLR) 4 and IL-1RI requirement for the cytokine-enhancing effects
      of the investigated HMGB1-ligand complexes. METHODS: Synovial fibroblasts
      obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients were
      stimulated with HMGB1 alone or in complex with LPS, IL-1alpha or IL-1beta. Tumour
      necrosis factor (TNF) production was determined by enzyme-linked immunospot assay
      (ELISPOT) assessment. Levels of IL-10, IL-1-beta, IL-6 and IL-8 were measured
      using Cytokine Bead Array and matrix metalloproteinase (MMP) 3 production was
      determined by ELISA. RESULTS: Stimulation with HMGB1 in complex with LPS, IL
      1alpha or IL-1beta enhanced production of TNF, IL-6 and IL-8. HMGB1 in complex
      with IL-1beta increased MMP production from both RASF and OASF. The cytokine
      production was inhibited by specific receptor blockade using detoxified LPS or IL
      1 receptor antagonist, indicating that the synergistic effects were mediated
      through the partner ligand-reciprocal receptors TLR4 and IL-1RI, respectively.
      CONCLUSIONS: HMGB1 in complex with LPS, IL-1alpha or IL-1beta boosted
      proinflammatory cytokine- and MMP production in synovial fibroblasts from RA and
      OA patients. A mechanism for the pathogenic role of HMGB1 in arthritis could thus
      be through enhancement of inflammatory and destructive mechanisms induced by
      other proinflammatory mediators present in the arthritic joint.

PMID- 21871095
TI  - Results of clinicians using a therapeutic robotic system in an inpatient stroke
      rehabilitation unit.
AB  - BACKGROUND: Physical rehabilitation is an area where robotics could contribute
      significantly to improved motor return for individuals following a stroke. This
      paper presents the results of a preliminary randomized controlled trial (RCT) of
      a robot system used in the rehabilitation of the paretic arm following a stroke.
      METHODS: The study's objectives were to explore the efficacy of this new type of
      robotic therapy as compared to standard physiotherapy treatment in treating the
      post-stroke arm; to evaluate client satisfaction with the proposed robotic
      system; and to provide data for sample size calculations for a proposed larger
      multicenter RCT. Twenty clients admitted to an inpatient stroke rehabilitation
      unit were randomly allocated to one of two groups, an experimental (robotic arm
      therapy) group or a control group (conventional therapy). An occupational
      therapist blinded to patient allocation administered two reliable measures, the
      Chedoke Arm and Hand Activity Inventory (CAHAI-7) and the Chedoke McMaster Stroke
      Assessment of the Arm and Hand (CMSA) at admission and discharge. For both
      groups, at admission, the CMSA motor impairment stage of the affected arm was
      between 1 and 3. RESULTS: Data were compared to determine the effectiveness of
      robot-assisted versus conventional therapy treatments. At the functional level,
      both groups performed well, with improvement in scores on the CAHAI-7 showing
      clinical and statistical significance. The CAHAI-7 (range7-49) is a measure of
      motor performance using functional items. Individuals in the robotic therapy
      group, on average, improved by 62% (95% CI: 26% to 107%) while those in the
      conventional therapy group changed by 30% (95% CI: 4% to 61%). Although
      performance on this measure is influenced by hand recovery, our results showed
      that both groups had similar stages of motor impairment in the hand. Furthermore,
      the degree of shoulder pain, as measured by the CMSA pain inventory scale, did
      not worsen for either group over the course of treatment. CONCLUSION: Our
      findings indicated that robotic arm therapy alone, without additional physical
      therapy interventions tailored to the paretic arm, was as effective as standard
      physiotherapy treatment for all responses and more effective than conventional
      treatment for the CMSA Arm (p = 0.04) and Hand (p = 0.04). At the functional
      level, both groups performed equally well.

PMID- 21871096
TI  - An analysis of national target groups for monovalent 2009 pandemic influenza
      vaccine and trivalent seasonal influenza vaccines in 2009-10 and 2010-11.
AB  - BACKGROUND: Vaccination is generally considered to be the best primary prevention
      measure against influenza virus infection. Many countries encourage specific
      target groups of people to undertake vaccination, often with financial subsidies
      or a priority list. To understand differential patterns of national target groups
      for influenza vaccination before, during and after the 2009 influenza pandemic,
      we reviewed and analyzed the country-specific policies in the corresponding time
      periods. METHODS: Information on prioritized groups targeted to receive seasonal
      and pandemic influenza vaccines was derived from a multi-step internet search of
      official health department websites, press releases, media sources and academic
      journal articles. We assessed the frequency and consistency of targeting 20
      different groups within populations which are associated with age, underlying
      medical conditions, role or occupations among different countries and vaccines.
      Information on subsidies provided to specific target groups was also extracted.
      RESULTS: We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines),
      72 (monovalent pandemic 2009-10 vaccine) and 34 (seasonal 2010 and 2010-11
      vaccines) countries. In 2009-10, the elderly, those with chronic illness and
      health care workers were common targets for the seasonal vaccine. Comparatively,
      the elderly, care home residents and workers, animal contacts and close contacts
      were less frequently targeted to receive the pandemic vaccine. Pregnant women,
      obese persons, essential community workers and health care workers, however, were
      more commonly targeted. After the pandemic, pregnant women, obese persons, health
      care and care home workers, and close contacts were more commonly targeted to
      receive the seasonal vaccine compared to 2009-10, showing continued influence
      from the pandemic. Many of the countries provided free vaccines, partial
      subsidies, reimbursements or national health insurance coverage to specific
      target groups and over one-third of the countries offered universal subsidy
      regarding the pandemic vaccine. There was also some inconsistency between
      countries in target groups. CONCLUSIONS: Differences in target groups between
      countries may reflect variable objectives as well as uncertainties regarding the
      transmission dynamics, severity and age-specific immunity against influenza
      viruses before and after vaccination. Clarification on these points is essential
      to elucidate optimal and object-oriented vaccination strategies.

PMID- 21871097
TI  - Progression to microalbuminuria in patients with type 1 diabetes: a seven-year
      prospective study.
AB  - BACKGROUND: The presence of microalbuminuria can be associated with overt
      nephropathy and cardiovascular disease in patients with type 1 diabetes (T1D). We
      aimed to determine the incidence and evaluate the baseline predictors for the
      development of microalbuminuria in patients with T1D. METHODS: This study is a
      longitudinal cohort study of 122 normoalbuminuric patients with T1D who were
      receiving routine clinical care at baseline. A detailed medical history was
      taken, and a physical examination was performed at baseline. All of the patients
      were regularly examined for diabetes-associated complications. An analysis of
      predictors was performed using the Cox regression. RESULTS: Over 6.81 (3.59-9.75)
      years of follow-up, 50 (41%) of the patients developed microalbuminuria. The
      incidence density was 6.79/100 people per year (95% CI 5.04-8.95), and the
      microalbuminuria developed after 5.9 (2.44-7.76) and 11 (5-15) years of follow-up
      and diabetes duration, respectively. After an individual Cox regression, the
      baseline variables associated with the development of microalbuminuria were age,
      age at diagnosis, duration of diabetes, systolic and diastolic blood pressure,
      fasting glycemia, body mass index (BMI), total cholesterol and triglycerides
      levels, cholesterol/HDL ratio and a family history of type 2 diabetes.After a
      multivariate Cox regression, the only independent factors associated with the
      development of microalbuminuria were BMI [HR 1.12 (1.03-1.21)] and
      cholesterol/HDL ratio [HR 1.32 (1.05-1.67)]. CONCLUSIONS: A higher BMI and
      cholesterol/HDL ratio increased the risk of developing microalbuminuria in young
      patients with T1D after a short follow-up. Both risk factors are modifiable and
      should be identified early and followed closely.

PMID- 21871098
TI  - Calcium sparks in the intact gerbil spiral modiolar artery.
AB  - BACKGROUND: Calcium sparks are ryanodine receptor mediated transient calcium
      signals that have been shown to hyperpolarize the membrane potential by
      activating large conductance calcium activated potassium (BK) channels in
      vascular smooth muscle cells. Along with voltage-dependent calcium channels, they
      form a signaling unit that has a vasodilatory influence on vascular diameter and
      regulation of myogenic tone. The existence and role of calcium sparks has
      hitherto been unexplored in the spiral modiolar artery, the end artery that
      controls blood flow to the cochlea. The goal of the present study was to
      determine the presence and properties of calcium sparks in the intact gerbil
      spiral modiolar artery. RESULTS: Calcium sparks were recorded from smooth muscle
      cells of intact arteries loaded with fluo-4 AM. Calcium sparks occurred with a
      frequency of 2.6 Hz, a rise time of 17 ms and a time to half-decay of 20 ms.
      Ryanodine reduced spark frequency within 3 min from 2.6 to 0.6 Hz. Caffeine (1
      mM) increased spark frequency from 2.3 to 3.3 Hz and prolonged rise and half
      decay times from 17 to 19 ms and from 20 to 23 ms, respectively. Elevation of
      potassium (3.6 to 37.5 mM), presumably via depolarization, increased spark
      frequency from 2.4 to 3.2 Hz. Neither ryanodine nor depolarization changed rise
      or decay times. CONCLUSIONS: This is the first characterization of calcium sparks
      in smooth muscle cells of the spiral modiolar artery. The results suggest that
      calcium sparks may regulate the diameter of the spiral modiolar artery and
      cochlear blood flow.

PMID- 21871099
TI  - Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus:
      genomic organization and UTRs characterization.
AB  - BACKGROUND: The heat stress suffered by Leishmania sp during its digenetic life
      cycle is a key trigger for its stage differentiation. In Leishmania subgenera two
      classes of HSP70 genes differing in their 3' UTR were described. Although the
      presence of HSP70-I genes was previously suggested in Leishmania (Viannia)
      braziliensis, HSP70-II genes had been reluctant to be uncovered. RESULTS: Here,
      we report the existence of two types of HSP70 genes in L. braziliensis and the
      genomic organization of the HSP70 locus. RT-PCR experiments were used to map the
      untranslated regions (UTR) of both types of genes. The 3' UTR-II has a low
      sequence identity (55-57%) when compared with this region in other Leishmania
      species. In contrast, the 5' UTR, common to both types of genes, and the 3' UTR-I
      were found to be highly conserved among all Leishmania species (77-81%). Southern
      blot assays suggested that L. braziliensis HSP70 gene cluster may contain around
      6 tandemly-repeated HSP70-I genes followed by one HSP70-II gene, located at
      chromosome 28. Northern blot analysis indicated that levels of both types of
      mRNAs are not affected by heat shock. CONCLUSIONS: This study has led to
      establishing the composition and structure of the HSP70 locus of L. braziliensis,
      complementing the information available in the GeneDB genome database for this
      species. L. braziliensis HSP70 gene regulation does not seem to operate by mRNA
      stabilization as occurs in other Leishmania species.

PMID- 21871100
TI  - Reduction of social inequalities in life expectancy in a city of Southeastern
      Brazil.
AB  - BACKGROUND: Around the world the life expectancy at birth has risen steadily over
      time. However, this increase in life years is not equally distributed among
      different social segments of the population. Studies have demonstrated that
      social groups living in deprived areas have a shorter life expectancy at birth in
      comparison to affluent ones. The aim of this study was to evaluate inequalities
      in life expectancy by socioeconomic strata in a city with one million inhabitants
      in Southeastern Brazil, in 2000 and 2005. METHODS: Through an ecological
      approach, the 49 areas of health care units of the city were classified into
      three socioeconomic strata, defined according to variables of income and
      educational level of the heads of household obtained from the 2000 Census. Life
      tables were constructed by sex for each of the three socioeconomic strata in 2000
      and 2005. RESULTS: The life expectancy at birth for men and women living in poor
      areas was 6.9 and 5.5 years lower in comparison to the affluent ones in 2000.
      Between 2000 and 2005, these social inequalities in life expectancy at birth
      reduced, since the groups with lower socioeconomic level had gained more life
      years. The increase in life expectancy at birth experienced by areas with worse
      living conditions was 3 times higher than the increment estimated for prosperous
      areas for both sexes. Males had the greatest gain in life years, leading to a
      narrowing of gender differentials in life expectancy between 2000 and 2005.
      CONCLUSIONS: The reduction of social inequalities in life expectancy suggests
      that living and health conditions have improved over time, due to social and
      health policies. The expansion of both health care coverage and cash transfer
      policies could have had positive effects on mortality reduction and on the
      consequent increase in the life expectancy, especially for the poor population.

PMID- 21871101
TI  - Prognosticators and risk grouping in patients with lung metastasis from
      nasopharyngeal carcinoma: a more accurate and appropriate assessment of
      prognosis.
AB  - BACKGROUND: Lung metastases arising from nasopharyngeal carcinomas (NPC) have a
      relatively favourable prognosis. The purpose of this study was to identify the
      prognostic factors and to establish a risk grouping in patients with lung
      metastases from NPC. METHODS: A total of 198 patients who developed lung
      metastases from NPC after primary therapy were retrospectively recruited from
      January 1982 to December 2000. Univariate and multivariate analyses of clinical
      variables were performed using Cox proportional hazards regression models.
      Actuarial survival rates were plotted against time using the Kaplan-Meier method,
      and log-rank testing was used to compare the differences between the curves.
      RESULTS: The median overall survival (OS) period and the lung metastasis survival
      (LMS) period were 51.5 and 20.9 months, respectively. After univariate and
      multivariate analyses of the clinical variables, age, T classification, N
      classification, site of metastases, secondary metastases and disease-free
      interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of
      metastases and secondary metastases were related to LMS. The prognoses of the low
      (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based
      on these factors were significantly different. The 3-, 5- and 10-year survival
      rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001)
      were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%.
      CONCLUSIONS: In this study, clinical variables provided prognostic indicators of
      survival in NPC patients with lung metastases. Risk subsets would help in a more
      accurate assessment of a patient's prognosis in the clinical setting and could
      facilitate the establishment of patient-tailored medical strategies and supports.

PMID- 21871102
TI  - Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy
      and the effects of tumor necrosis factor-alpha antagonism.
AB  - INTRODUCTION: Tumor necrosis factor-alpha (TNFalpha) has received significant
      attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism
      to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can
      attenuate heightened nociception resulting from lumbar radiculopathy in the
      preclinical model. Less is known about the potential impact of TNF antagonism on
      gait compensations, despite being of clinical relevance. In this study, we expand
      on previous descriptions of gait compensations resulting from lumbar
      radiculopathy in the rat and describe the ability of local TNF antagonism to
      prevent the development of gait compensations, altered weight bearing, and
      heightened nociception. METHODS: Eighteen male Sprague-Dawley rats were
      investigated for mechanical sensitivity, weight-bearing, and gait pre- and post
      operatively. For surgery, tail nucleus pulposus (NP) tissue was collected and the
      right L5 dorsal root ganglion (DRG) was exposed (Day 0). In sham animals, NP
      tissue was discarded (n = 6); for experimental animals, autologous NP was placed
      on the DRG with or without 20 MUg of soluble TNF receptor type II (sTNFRII, n = 6
      per group). Spatiotemporal gait characteristics (open arena) and mechanical
      sensitivity (von Frey filaments) were assessed on post-operative Day 5; gait
      dynamics (force plate arena) and weight-bearing (incapacitance meter) were
      assessed on post-operative Day 6. RESULTS: High-speed gait characterization
      revealed animals with NP alone had a 5% decrease in stance time on their affected
      limbs on Day 5 (P <=0.032). Ground reaction force analysis on Day 6 aligned with
      temporal changes observed on Day 5, with vertical impulse reduced in the affected
      limb of animals with NP alone (area under the vertical force-time curve, P
      <0.02). Concordant with gait, animals with NP alone also had some evidence of
      affected limb mechanical allodynia on Day 5 (P = 0.08) and reduced weight-bearing
      on the affected limb on Day 6 (P <0.05). Delivery of sTNFRII at the time of NP
      placement ameliorated signs of mechanical hypersensitivity, imbalanced weight
      distribution, and gait compensations (P <0.1). CONCLUSIONS: Our data indicate
      gait characterization has value for describing early limb dysfunctions in pre
      clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented
      the development of gait compensations subsequent to lumbar radiculopathy in our
      model.

PMID- 21871103
TI  - Product Development Partnerships: Case studies of a new mechanism for health
      technology innovation.
AB  - There is a continuing need for new health technologies to address the disease
      burdens of developing countries. In the last decade Product Development
      Partnerships (PDP) have emerged that are making important contributions to the
      development of these technologies. PDPs are a form of public private partnerships
      that focus on health technology development. PDPs reflect the current phase in
      the history of health technology development: the Era of Partnerships, in which
      the public and private sectors have found productive ways to collaborate.
      Successful innovation depends on addressing six determinants of innovation. We
      examine four case studies of PDPs and show how they have addressed the six
      determinants to achieve success.

PMID- 21871104
TI  - Clinical profile and outcome of surgical treatment of perforated peptic ulcers in
      Northwestern Tanzania: A tertiary hospital experience.
AB  - BACKGROUND: Perforated peptic ulcer is a serious complication of peptic ulcers
      with potential risk of grave complications. There is paucity of published reports
      on perforated peptic ulcer disease in our local environment. This study was
      conducted to evaluate the clinical presentation, management and outcome of
      patients with peptic ulcer perforation in our setting and to identify predictors
      of outcome of these patients. METHODS: This was a combined retrospective and
      prospective study of patients who were operated for perforated peptic ulcers at
      Bugando Medical Centre between April 2006 and March 2011. Data were collected
      using a pre-tested and coded questionnaire and analyzed using SPSS computer
      software version 15.0. Ethical approval to conduct the study was obtained from
      relevant authority before the commencement of the study. RESULTS: A total of 84
      patients were studied. Males outnumbered females by a ratio of 1.3: 1. Their
      median age was 28 years and the modal age group was 21-30 years. The median
      duration of illness was 5.8 days. The majority of patients (69.0%) had no
      previous history of treatment for peptic ulcer disease. The use of non-steroidal
      anti-inflammatory drugs, alcohol and smoking was reported in 10.7%, 85.7% and
      64.3% respectively. Eight (9.5%) patients were HIV positive with a median CD4
      count of 220 cells/MUl. Most perforations were located on the duodenum {90.4%)
      with the duodenal to gastric ulcers ratio of 12.7: 1. Graham's omental patch
      (Graham's omentopexy) of the perforations was performed in 83.3% of cases.
      Complication and mortality rates were 29.8% and 10.7% respectively. The factors
      significantly related to complications were premorbid illness, HIV status, CD 4
      count < 200 cells/MUl, treatment delay and acute perforation (P < 0.001).
      Mortality rate was high in patients who had age >= 40 years, delayed presentation
      (>24 hrs), shock at admission (systolic BP < 90 mmHg), HIV positivity, low CD4
      count (<200 cells/MUl), gastric ulcers, concomitant diseases and presence of
      complications (P < 0.001). The median overall length of hospital stay was 14
      days. Excellent results using Visick's grading system were obtained in 82.6% of
      surviving patients. CONCLUSION: Perforation of peptic ulcer remains a frequent
      clinical problem in our environment predominantly affecting young males not known
      to suffer from PUD. Simple closure with omental patch followed by Helicobacter
      pylori eradication was effective with excellent results in majority of survivors
      despite patients' late presentation in our center.

PMID- 21871105
TI  - Cyclophilin A enhances cell proliferation and tumor growth of liver fluke
      associated cholangiocarcinoma.
AB  - BACKGROUND: Cyclophilin A (CypA) expression is associated with malignant
      phenotypes in many cancers. However, the role and mechanisms of CypA in liver
      fluke-associated cholangiocarcinoma (CCA) are not presently known. In this study,
      we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as
      well as regulation mechanisms of CypA in tumor growth using CCA cell lines.
      METHODS: CypA expression was determined by real time RT-PCR, Western blot or
      immunohistochemistry. CypA silence or overexpression in CCA cells was achieved
      using gene delivery techniques. Cell proliferation was assessed using MTS assay
      or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was
      determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was
      assessed by Western blot. RESULTS: CypA was upregulated in 68% of CCA tumor
      tissues. Silencing CypA significantly suppressed cell proliferation in several
      CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase
      (PPIase) activity using cyclosporin A (CsA) decreased cell proliferation. In
      contrast, overexpression of CypA resulted in 30% to 35% increases in
      proliferation of CCA cell lines. Interestingly, neither silence nor
      overexpression of CypA affected cell proliferation of a non-tumor human
      cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2
      activity in CCA M139 cells by using both transient and stable knockdown methods.
      In the in vivo study, there was a 43% reduction in weight of tumors derived from
      CypA-silenced CCA cell lines compared with control vector CCA tumors in mice;
      these tumors with stable CypA silencing showed a reduced cell proliferation.
      CONCLUSIONS: CypA is upregulated in majority of CCA patients' tissues and confers
      a significant growth advantage in CCA cells. Suppression of CypA expression
      decreases proliferation of CCA cell lines in vitro and reduces tumor growth in
      the nude mouse model. Inhibition of CypA activity also reduces CCA cell
      proliferation. The ERK1/2 pathway may be involved in the CypA-mediated CCA cell
      proliferation. Thus, CypA may represent an important new therapeutic target for
      liver fluke-associated CCA.

PMID- 21871106
TI  - An intronic SNP in the thyroid hormone receptor beta gene is associated with
      pituitary cell-specific over-expression of a mutant thyroid hormone receptor
      beta2 (R338W) in the index case of pituitary-selective resistance to thyroid
      hormone.
AB  - BACKGROUND: The syndrome of resistance to thyroid hormone (RTH) is caused by
      mutations in the thyroid hormone receptor beta gene (THRB). The syndrome varies
      from asymptomatic to diffuse hypothyroidism, to pituitary-selective resistance
      with predominance of hyperthyroid signs and symptoms. The wide spectrum of
      clinical presentation is not completely attributable to specific THRB mutations.
      The THRB gene encodes two main isoforms, TR beta1 which is widely distributed,
      and TR beta2, whose expression is limited to the cochlea, retina, hypothalamus,
      and pituitary. Recent data demonstrated that in mice an intron enhancer region
      plays a critical role in the pituitary expression of the beta2 isoform of the
      receptor. We thus hypothesized that polymorphisms in the human homologous region
      could modulate the pituitary expression of the mutated gene contributing to the
      clinical presentation of RTH. METHODS: Screening and in vitro characterization of
      polymorphisms of the intron enhancer region of the THRB gene in the index case of
      pituitary-selective RTH. RESULTS: The index case of pituitary-selective
      resistance is characterized by the missense R338W exon 9 mutation in cis with two
      common SNPs, rs2596623T and rs2596622C, located in the intron enhancer region of
      the THRB gene. Reporter gene assay experiments in GH3 pituitary-derived cells
      indicate that rs2596623T generates an increased pituitary cell-specific activity
      of the TR beta2 promoter suggesting that rs2596623T leads to pituitary over
      expression of the mutant allele. CONCLUSIONS: The combined coding mutation and
      non-coding SNP therefore generate a tissue-specific dominant-negative condition
      recapitulating the patient's peculiar phenotype. This case illustrates the role
      of regulatory regions in modifying the clinical presentation of genetic diseases.

PMID- 21871107
TI  - Mathematical model insights into arsenic detoxification.
AB  - BACKGROUND: Arsenic in drinking water, a major health hazard to millions of
      people in South and East Asia and in other parts of the world, is ingested
      primarily as trivalent inorganic arsenic (iAs), which then undergoes hepatic
      methylation to methylarsonic acid (MMAs) and a second methylation to
      dimethylarsinic acid (DMAs). Although MMAs and DMAs are also known to be toxic,
      DMAs is more easily excreted in the urine and therefore methylation has generally
      been considered a detoxification pathway. A collaborative modeling project
      between epidemiologists, biologists, and mathematicians has the purpose of
      explaining existing data on methylation in human studies in Bangladesh and also
      testing, by mathematical modeling, effects of nutritional supplements that could
      increase As methylation. METHODS: We develop a whole body mathematical model of
      arsenic metabolism including arsenic absorption, storage, methylation, and
      excretion. The parameters for arsenic methylation in the liver were taken from
      the biochemical literature. The transport parameters between compartments are
      largely unknown, so we adjust them so that the model accurately predicts the
      urine excretion rates of time for the iAs, MMAs, and DMAs in single dose
      experiments on human subjects. RESULTS: We test the model by showing that, with
      no changes in parameters, it predicts accurately the time courses of urinary
      excretion in mutiple dose experiments conducted on human subjects. Our main
      purpose is to use the model to study and interpret the data on the effects of
      folate supplementation on arsenic methylation and excretion in clinical trials in
      Bangladesh. Folate supplementation of folate-deficient individuals resulted in a
      14% decrease in arsenicals in the blood. This is confirmed by the model and the
      model predicts that arsenicals in the liver will decrease by 19% and arsenicals
      in other body stores by 26% in these same individuals. In addition, the model
      predicts that arsenic methyltransferase has been upregulated by a factor of two
      in this population. Finally, we also show that a modification of the model gives
      excellent fits to the data on arsenic metabolism in human cultured hepatocytes.
      CONCLUSIONS: The analysis of the Bangladesh data using the model suggests that
      folate supplementation may be more effective at reducing whole body arsenic than
      previously expected. There is almost no data on the upregulation of arsenic
      methyltransferase in populations chronically exposed to arsenic. Our model
      predicts upregulation by a factor of two in the Bangladesh population studied.
      This prediction should be verified since it could have important public health
      consequences both for treatment strategies and for setting appropriate limits on
      arsenic in drinking water. Our model has compartments for the binding of
      arsenicals to proteins inside of cells and we show that these comparments are
      necessary to obtain good fits to data. Protein-binding of arsenicals should be
      explored in future biochemical studies.

PMID- 21871108
TI  - Immunodetection of occult eosinophils in lung tissue biopsies may help predict
      survival in acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) is a serious respiratory disorder for which
      therapy is primarily supportive once infection is excluded. Surgical lung biopsy
      may rule out other diagnoses, but has not been generally useful for therapy
      decisions or prognosis in this setting. Importantly, tissue and peripheral blood
      eosinophilia, the hallmarks of steroid-responsive acute eosinophilic pneumonia,
      are not commonly linked with ALI. We hypothesized that occult eosinophilic
      pneumonia may explain better outcomes for some patients with ALI. METHODS:
      Immunohistochemistry using a novel monoclonal antibody recognizing eosinophil
      peroxidase (EPX-mAb) was used to assess intrapulmonary eosinophil
      accumulation/degranulation. Lung biopsies from ALI patients (n = 20) were
      identified following review of a pathology database; 45% of which (i.e., 9/20)
      displayed classical diffuse alveolar damage (ALI-DAD). Controls were obtained
      from uninvolved tissue in patients undergoing lobectomy for lung cancer (n = 10).
      Serial biopsy sections were stained with hematoxylin and eosin (H&E) and
      subjected to EPX-mAb immunohistochemistry. RESULTS: EPX-mAb immunohistochemistry
      provided a >40-fold increased sensitivity to detect eosinophils in the lung
      relative to H&E stained sections. This increased sensitivity led to the
      identification of higher numbers of eosinophils in ALI patients compared with
      controls; differences using H&E staining alone were not significant. Clinical
      assessments showed that lung infiltrating eosinophil numbers were higher in ALI
      patients that survived hospitalization compared with non-survivors. A similar
      conclusion was reached quantifying eosinophil degranulation in each biopsy.
      CONCLUSION: The enhanced sensitivity of EPX-mAb immunohistochemistry uniquely
      identified eosinophil accumulation/degranulation in patients with ALI relative to
      controls. More importantly, this method was a prognostic indicator of patient
      survival. These observations suggest that EPX-mAb immunohistochemistry may
      represent a diagnostic biomarker identifying a subset of ALI patients with
      improved clinical outcomes.

PMID- 21871109
TI  - Circulating CD133+CD34+ progenitor cells inversely correlate with soluble ICAM-1
      in early ischemic stroke patients.
AB  - BACKGROUND AND PURPOSE: Both endothelial progenitor cells (EPC) and markers of
      neuroinflammation are candidate biomarkers for stroke severity and outcome
      prediction. A relationship between EPC and neuroinflammatory markers in early
      stroke is not fully elucidated. The objectives were to investigate correlations
      between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E
      selectin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, endothelin (ET)
      1, markers of tissue injury (matrix metalloproteinases (MMP)-9 and tissue
      inhibitor of matrix metalloproteinases (TIMP)-1) in early stroke patients.
      METHODS: We prospectively recruited symptomatic patients with ischemic
      cerebrovascular disease. We assessed stroke severity by using of acute (diffusion
      weighted imaging (DWI) and final lesion volumes (fluid attenuated inversion
      recovery (FLAIR). We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9,
      TIMP-1 and plasma TNF-alpha, IL-6, ET-1 by ELISA, and quantified EPC in
      mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD)
      age 62(14), with admission National Institutes of Health Stroke Scale (NIHSS)
      10(8)) selected from 175 patients with imaging confirmed ischemic stroke. Non
      parametric statistics, univariate and multivariate analysis were used. RESULTS:
      Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r
      = -0.6, p < 0.01) and on day 3 (r = -0.967, p < 0.001). This correlation remained
      significant after adjustment for age and NIHSS (beta -0.992, p < 0.004), for
      glucose and systolic blood pressure (beta -0.86, p < 0.005), and for white blood
      cells and hematocrit (beta -1.057, p < 0.0001) on day 3. MMP-9 (r = 0.509, p <
      0.04) and MMP-9/TIMP-1 (r = 0.59, p < 0.013) on day 1 correlated with acute
      lesion volume. Both IL-6 (r = 0.624, p < 0.01) and MMP-9/TIMP-1 (r = 0.56, p <
      0.02) correlated with admission NIHSS. CONCLUSION: Our study showed that high
      ICAM-1 is associated with low CD133+CD34+subset of EPC. Biomarkers of
      neuroinflammation may predict tissue injury and stroke severity in early
      ischemia.

PMID- 21871110
TI  - Studying the correlation between different word sense disambiguation methods and
      summarization effectiveness in biomedical texts.
AB  - BACKGROUND: Word sense disambiguation (WSD) attempts to solve lexical ambiguities
      by identifying the correct meaning of a word based on its context. WSD has been
      demonstrated to be an important step in knowledge-based approaches to automatic
      summarization. However, the correlation between the accuracy of the WSD methods
      and the summarization performance has never been studied. RESULTS: We present
      three existing knowledge-based WSD approaches and a graph-based summarizer. Both
      the WSD approaches and the summarizer employ the Unified Medical Language System
      (UMLS) Metathesaurus as the knowledge source. We first evaluate WSD directly, by
      comparing the prediction of the WSD methods to two reference sets: the NLM WSD
      dataset and the MSH WSD collection. We next apply the different WSD methods as
      part of the summarizer, to map documents onto concepts in the UMLS Metathesaurus,
      and evaluate the summaries that are generated. The results obtained by the
      different methods in both evaluations are studied and compared. CONCLUSIONS: It
      has been found that the use of WSD techniques has a positive impact on the
      results of our graph-based summarizer, and that, when both the WSD and
      summarization tasks are assessed over large and homogeneous evaluation
      collections, there exists a correlation between the overall results of the WSD
      and summarization tasks. Furthermore, the best WSD algorithm in the first task
      tends to be also the best one in the second. However, we also found that the
      improvement achieved by the summarizer is not directly correlated with the WSD
      performance. The most likely reason is that the errors in disambiguation are not
      equally important but depend on the relative salience of the different concepts
      in the document to be summarized.

PMID- 21871111
TI  - The plausible reason why the length of 5' untranslated region is unrelated to
      organismal complexity.
AB  - BACKGROUND: Organismal complexity is suggested to increase with the complexity of
      transcriptional and translational regulations. Supporting this notion is a recent
      study that demonstrated a higher level of tissue-specific gene expression in
      human than in mouse. However, whether this correlation can be extended beyond
      mammals remains unclear. In addition, 5' untranslated regions (5'UTRs), which
      have undergone stochastic elongation during evolution and potentially included an
      increased number of regulatory elements, may have played an important role in the
      emergence of organismal complexity. Although the lack of correlation between
      5'UTR length and organismal complexity has been proposed, the underlying
      mechanisms remain unexplored. RESULTS: In this study, we select the number of
      cell types as the measurement of organismal complexity and examine the
      correlation between (1) organismal complexity and transcriptional regulatory
      complexity; and (2) organismal complexity and 5'UTR length by comparing the
      5'UTRs and multiple-tissue expression profiles of human (Homo sapiens), mouse
      (Mus musculus), and fruit fly (Drosophila melanogaster). The transcriptional
      regulatory complexity is measured by using the tissue specificity of gene
      expression and the ratio of non-constitutively expressed to constitutively
      expressed genes. We demonstrate that, whereas correlation (1) holds well in the
      three-way comparison, correlation (2) is not true. Results from a larger dataset
      that includes more than 15 species, ranging from yeast to human, also reject
      correlation (2). The reason for the failure of correlation (2) may be ascribed
      to: Firstly, longer 5'UTRs do not contribute to increased tissue specificity of
      gene expression. Secondly, the increased numbers of common translational
      regulatory elements in longer 5'UTRs do not lead to increased organismal
      complexity. CONCLUSIONS: Our study has extended the evidence base for the
      correlation between organismal complexity and transcriptional regulatory
      complexity from mammals to fruit fly, the representative model organism of
      invertebrates. Furthermore, our results suggest that the elongation of 5'UTRs
      alone can not lead to the increase in regulatory complexity or the emergence of
      organismal complexity.

PMID- 21871112
TI  - Precision of the transpulmonary thermodilution measurements.
AB  - INTRODUCTION: We wanted to determine the number of cold bolus injections that are
      necessary for achieving an acceptable level of precision for measuring cardiac
      index (CI), indexed global end-diastolic volume (GEDVi) and indexed extravascular
      lung water (EVLWi) by transpulmonary thermodilution. METHODS: We included 91
      hemodynamically stable patients (age 59 (25% to 75% interquartile range: 39 to
      79) years, simplified acute physiologic score (SAPS)II 59 (53 to 65), 56% under
      norepinephrine) who were monitored by a PiCCO2 device. We performed five
      successive cold saline (15 mL, 6  degrees C) injections and recorded the
      measurements of CI, GEDVi and EVLWi. RESULTS: Considering five boluses, the
      coefficient of variation (CV, calculated as standard deviation divided by the
      mean of the five measurements) was 7 (5 to 11)%, 7 (5 to 12)% and 7 (6 to 12)%
      for CI, GEDVi and EVLWi, respectively. If the results of two bolus injections
      were averaged, the precision (2 * CV/? number of boluses) was 10 (7 to 15)%, 10
      (7 to 17)% and 8 (7 to 14)% for CI, GEDVi and EVLWi, respectively. If the results
      of three bolus injections were averaged, the precision dropped below 10%, that
      is, the cut-off that is generally considered as acceptable (8 (6 to 12)%, 8 (6 to
      14)% and 8 (7 to 14)% for CI, GEDVi and EVLWi, respectively). If two injections
      were performed, the least significant change, that is, the minimal change in
      value that could be trusted to be significant, was 14 (10 to 21)%, 14 (10 to 24)%
      and 14 (11 to 23)% for CI, GEDVi and EVLWi, respectively. If three injections
      were performed, the least significant change was 12 (8 to 17)%, 12 (8 to 19)% and
      12 (9 to 19)% for CI, GEDVi and EVLWi, respectively, that is, below the 15% cut
      off that is usually considered as clinically relevant. CONCLUSIONS: These results
      support the injection of at least three cold boluses for obtaining an acceptable
      precision when transpulmonary thermodilution is used for measuring CI, GEDVi and
      EVLWi.

PMID- 21871113
TI  - Diet, physical exercise and cognitive behavioral training as a combined workplace
      based intervention to reduce body weight and increase physical capacity in health
      care workers - a randomized controlled trial.
AB  - BACKGROUND: Health care workers comprise a high-risk workgroup with respect to
      deterioration and early retirement. There is high prevalence of obesity and many
      of the workers are overweight. Together, these factors play a significant role in
      the health-related problems within this sector. The present study evaluates the
      effects of the first 3-months of a cluster randomized controlled lifestyle
      intervention among health care workers. The intervention addresses body weight,
      general health variables, physical capacity and musculoskeletal pain. METHODS: 98
      female, overweight health care workers were cluster-randomized to an intervention
      group or a reference group. The intervention consisted of an individually dietary
      plan with an energy deficit of 1200 kcal/day (15 min/hour), strengthening
      exercises (15 min/hour) and cognitive behavioral training (30 min/hour) during
      working hours 1 hour/week. Leisure time aerobic fitness was planned for 2
      hour/week. The reference group was offered monthly oral presentations. Body
      weight, BMI, body fat percentage (bioimpedance), waist circumference, blood
      pressure, musculoskeletal pain, maximal oxygen uptake (maximal bicycle test), and
      isometric maximal muscle strength of 3 body regions were measured before and
      after the intervention period. RESULTS: In an intention-to-treat analysis from
      pre to post tests, the intervention group significantly reduced body weight with
      3.6 kg (p < 0.001), BMI from 30.5 to 29.2 (p < 0.001), body fat percentage from
      40.9 to 39.3 (p < 0.001), waist circumference from 99.7 to 95.5 cm (p < 0.001)
      and blood pressure from 134/85 to 127/80 mmHg (p < 0.001), with significant
      difference between the intervention and control group (p < 0.001) on all
      measures. No effect of intervention was found in musculoskeletal pain, maximal
      oxygen uptake and muscle strength, but on aerobic fitness. CONCLUSION: The
      significantly reduced body weight, body fat, waist circumference and blood
      pressure as well as increased aerobic fitness in the intervention group show the
      great potential of workplace health promotion among this high-risk workgroup.
      Long-term effects of the intervention remain to be investigated. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01015716.

PMID- 21871114
TI  - Landmarks or panoramas: what do navigating ants attend to for guidance?
AB  - BACKGROUND: Insects are known to rely on terrestrial landmarks for navigation.
      Landmarks are used to chart a route or pinpoint a goal. The distant panorama,
      however, is often thought not to guide navigation directly during a familiar
      journey, but to act as a contextual cue that primes the correct memory of the
      landmarks. RESULTS: We provided Melophorus bagoti ants with a huge artificial
      landmark located right near the nest entrance to find out whether navigating ants
      focus on such a prominent visual landmark for homing guidance. When the landmark
      was displaced by small or large distances, ant routes were affected differently.
      Certain behaviours appeared inconsistent with the hypothesis that guidance was
      based on the landmark only. Instead, comparisons of panoramic images recorded on
      the field, encompassing both landmark and distal panorama, could explain most
      aspects of the ant behaviours. CONCLUSION: Ants navigating along a familiar route
      do not focus on obvious landmarks or filter out distal panoramic cues, but appear
      to be guided by cues covering a large area of their panoramic visual field,
      including both landmarks and distal panorama. Using panoramic views seems an
      appropriate strategy to cope with the complexity of natural scenes and the poor
      resolution of insects' eyes. The ability to isolate landmarks from the rest of a
      scene may be beyond the capacity of animals that do not possess a dedicated
      object-perception visual stream like primates.

PMID- 21871115
TI  - The mitochondrial genome of Sinentomon erythranum (Arthropoda: Hexapoda:
      Protura): an example of highly divergent evolution.
AB  - BACKGROUND: The phylogenetic position of the Protura, traditionally considered
      the most basal hexapod group, is disputed because it has many unique
      morphological characters compared with other hexapods. Although mitochondrial
      genome information has been used extensively in phylogenetic studies, such
      information is not available for the Protura. This has impeded phylogenetic
      studies on this taxon, as well as the evolution of the arthropod mitochondrial
      genome. RESULTS: In this study, the mitochondrial genome of Sinentomon erythranum
      was sequenced, as the first proturan species to be reported. The genome contains
      a number of special features that differ from those of other hexapods and
      arthropods. As a very small arthropod mitochondrial genome, its 14,491
      nucleotides encode 37 typical mitochondrial genes. Compared with other metazoan
      mtDNA, it has the most biased nucleotide composition with T = 52.4%, an extreme
      and reversed AT-skew of -0.351 and a GC-skew of 0.350. Two tandemly repeated
      regions occur in the A+T-rich region, and both could form stable stem-loop
      structures. Eighteen of the 22 tRNAs are greatly reduced in size with truncated
      secondary structures. The gene order is novel among available arthropod
      mitochondrial genomes. Rearrangements have involved in not only small tRNA genes,
      but also PCGs (protein-coding genes) and ribosome RNA genes. A large block of
      genes has experienced inversion and another nearby block has been reshuffled,
      which can be explained by the tandem duplication and random loss model. The most
      remarkable finding is that trnL2(UUR) is not located between cox1 and cox2 as
      observed in most hexapod and crustacean groups, but is between rrnL and nad1 as
      in the ancestral arthropod ground pattern. The "cox1-cox2" pattern was further
      confirmed in three more representative proturan species. The phylogenetic
      analyses based on the amino acid sequences of 13 mitochondrial PCGs suggest S.
      erythranum failed to group with other hexapod groups. CONCLUSIONS: The
      mitochondrial genome of S. erythranum shows many different features from other
      hexapod and arthropod mitochondrial genomes. It underwent highly divergent
      evolution. The "cox1-cox2" pattern probably represents the ancestral state for
      all proturan mitogenomes, and suggests a long evolutionary history for the
      Protura.

PMID- 21871116
TI  - De novo deletion in MECP2 in a monozygotic twin pair: a case report.
AB  - BACKGROUND: Rett syndrome (RTT) is a severe, progressive, neurodevelopmental
      disorder predominantly observed in females that leads to intellectual disability.
      Mutations and gross rearrangements in MECP2 account for a large proportion of
      cases with RTT. A limited number of twin pairs with RTT have also been reported
      in literature. CASE PRESENTATION: We investigated 13 year old, monozygotic twin
      females with RTT and some noticeable differences in development using a
      combinatorial approach of sequencing and Taqman assay. Monozygosity status of the
      twins was confirmed by informative microsatellite markers. CONCLUSIONS: The twins
      shared a de novo deletion in exon 3 in the MBD domain of MECP2. To the best of
      our knowledge, this is only the second report of genetic analysis of a
      monozygotic twin pair.

PMID- 21871117
TI  - Oxidative stress and antioxidant status in primary bone and soft tissue sarcoma.
AB  - BACKGROUND: Oxidative stress is characterised by an increased level of reactive
      oxygen species (ROS) that disrupts the intracellular reduction-oxidation (redox)
      balance and has been implicated in various diseases including cancer. Malignant
      tumors of connective tissue or sarcomas account for approximately 1% of all
      cancer diagnoses in adults and around 15% of paediatric malignancies per annum.
      There exists no information on the alterations of oxidant/antioxidant status of
      sarcoma patients in literature. This study was aimed to determine the levels of
      oxidative stress and antioxidant defence in patients with primary bone and soft
      tissue sarcoma and to investigate if there exists any significant differences in
      these levels between both the sarcomas. METHODS: The study cohort consisted of 94
      subjects; 20 soft tissue sarcoma, 27 primary bone sarcoma and 47 healthy
      controls. Malondialdehyde (MDA) and protein carbonyls were determined to assess
      their oxidative stress levels while antioxidant status was evaluated using
      catalase (CAT), superoxide dismutase (SOD), thiols and trolox equivalent
      antioxidant capacity (TEAC). RESULTS: Sarcoma patients showed significant
      increase in plasma and urinary MDA and serum protein carbonyl levels (p < 0.05)
      while significant decreases were noted in TEAC, thiols, CAT and SOD levels (p <
      0.05). No significant difference in oxidative damage was noted between both the
      sarcomas (p > 0.05). CONCLUSIONS: In conclusion, an increase in oxidative stress
      and decrease in antioxidant status is observed in both primary bone and soft
      tissue sarcomas with a similar extent of damage. This study offers the basis for
      further work on whether the manipulation of redox balance in patients with
      sarcoma represents a useful approach in the design of future therapies for bone
      disease.

PMID- 21871118
TI  - Primary retroperitoneal mucinous cystadenoma of borderline malignancy in a male
      patient. Case report and review of the literature.
AB  - BACKGROUND: Primary retroperitoneal mucinous cystadenoma of borderline malignancy
      represents a rare tumor, with unclear histogenesis, concerning almost exclusively
      women. Only two cases concerning male patients have been reported. CASE REPORT:
      We herein report a case of a 37 year old man undergone laparotomy for a sizable
      retroperitoneal tumor resulting after the histological examination to a primary
      retroperitoneal mucinous cystadenoma of borderline malignancy. CONCLUSION: This
      is the third case of primary retroperitoneal mucinous cystadenoma of borderline
      malignancy in a male patient reported in the literature. The preoperative
      diagnosis is impossible. Laparotomy constitutes the only diagnostic and curative
      approach.

PMID- 21871120
TI  - Stapler access and visibility in the deep pelvis: A comparative human cadaver
      study between a computerized right angle linear cutter versus a curved cutting
      stapler.
AB  - PURPOSE: Distal rectal stapling is often challenging because of limited space and
      visibility. We compared two stapling devices in the distal rectum in a cadaver
      study: the iDriveTM right angle linear cutter (RALC) (Covidien, New Haven, CT)
      and the CONTOUR(r) curved cutter (CC) (Ethicon Endo-Surgery, Cincinnati, OH).
      METHODS: Twelve male cadavers underwent pelvic dissection by 4 surgeons. After
      rectal mobilization as in a total mesorectal excision, the staplers were applied
      to the rectum as deep as possible in both the coronal and sagittal positions. The
      distance from the pelvic floor was measured for each application. A questionnaire
      rated the visibility and access of the stapling devices. Measurements were taken
      between pelvic landmarks to see what anatomic factors hinder the placement of a
      distal rectal stapler. RESULTS: The median (range) distance of the stapler from
      the pelvic floor in the coronal position for the RALC was 1.0 cm (0-4.0) vs. 2.0
      cm (0-5.0) for the CC, p = 0.003. In the sagittal position, the median distance
      was 1.6 cm (0-3.5) for the RALC and 3.3 cm (0-5.0) for the CC, p < 0.0001. The
      RALC scored better than the CC in respect to: 1. interference by the symphysis
      pubis, 2. number of stapler readjustments, 3. ease of placement in the pelvis, 4.
      impediment of visibility, 5. ability to hold and retain tissue, 6. visibility
      rating, and 7. access in the pelvis. A shorter distance between the tip of the
      coccyx and the pubic symphysis correlated with a longer distance of the stapler
      from the pelvic floor (p = 0.002). CONCLUSIONS: The RALC is superior to the CC in
      terms of access, visibility, and ease of placement in the deep pelvis. This could
      provide important clinical benefit to both patient and surgeon during difficult
      rectal surgery.

PMID- 21871119
TI  - Application of a diagnosis-based clinical decision guide in patients with neck
      pain.
AB  - BACKGROUND: Neck pain (NP) is a common cause of disability. Accurate and
      efficacious methods of diagnosis and treatment have been elusive. A diagnosis
      based clinical decision guide (DBCDG; previously referred to as a diagnosis-based
      clinical decision rule) has been proposed which attempts to provide the clinician
      with a systematic, evidence-based guide in applying the biopsychosocial model of
      care. The approach is based on three questions of diagnosis. The purpose of this
      study is to present the prevalence of findings using the DBCDG in consecutive
      patients with NP. METHODS: Demographic, diagnostic and baseline outcome measure
      data were gathered on a cohort of NP patients examined by one of three examiners
      trained in the application of the DBCDG. RESULTS: Data were gathered on 95
      patients. Signs of visceral disease or potentially serious illness were found in
      1%. Centralization signs were found in 27%, segmental pain provocation signs were
      found in 69% and radicular signs were found in 19%. Clinically relevant
      myofascial signs were found in 22%. Dynamic instability was found in 40%,
      oculomotor dysfunction in 11.6%, fear beliefs in 31.6%, central pain
      hypersensitivity in 4%, passive coping in 5% and depression in 2%. CONCLUSION:
      The DBCDG can be applied in a busy private practice environment. Further studies
      are needed to investigate clinically relevant means to identify central pain
      hypersensitivity, oculomotor dysfunction, poor coping and depression,
      correlations and patterns among the diagnostic components of the DBCDG as well as
      inter-examiner reliability, validity and efficacy of treatment based on the
      DBCDG.

PMID- 21871121
TI  - The role of tumor necrosis factor-alpha and TNF-alpha receptors in cerebral
      arteries following cerebral ischemia in rat.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic pro
      inflammatory cytokine, which is rapidly upregulated in the brain after injury.
      TNF-alpha acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the
      cell surface. The aim of this study was first to investigate if there is altered
      expression of TNF-alpha and TNF-alpha receptors in cerebral artery walls
      following global or focal ischemia, and after organ culture. Secondly, we asked
      if the expression was regulated via activation of the MEK-ERK1/2 pathway.
      METHODS: The hypothesis was tested in vivo after subarachnoid hemorrhage (SAH)
      and middle cerebral artery occlusion (MCAO), and in vitro by organ culture of
      isolated cerebral arteries. The localization and amount of TNF-alpha, TNF-alpha
      receptor 1 and 2 proteins were analysed by immunohistochemistry and western blot
      after 24 and 48 h of organ culture and at 48 h following SAH or MCAO. In
      addition, cerebral arteries were incubated for 24 or 48 h in the absence or
      presence of a B-Raf inhibitor (SB386023-b), a MEK- inhibitor (U0126) or an NF
      kappaB inhibitor (IMD-0354), and protein expression evaluated. RESULTS:
      Immunohistochemistry revealed enhanced expression of TNF-alpha, TNF-R1 and TNF-R2
      in the walls of cerebral arteries at 48 h after MCAO and SAH compared with
      control. Co-localization studies showed that TNF-alpha, TNF-R1 and TNF-R2 were
      primarily localized to the cell membrane and the cytoplasm of the smooth muscle
      cells (SMC). There was, in addition, some expression of TNF-R2 in the endothelial
      cells. Immunohistochemistry and western blot analysis showed that these proteins
      were upregulated after 24 and 48 h in culture, and this upregulation reached an
      apparent maximum at 48 h of organ culture. Treatment with U0126 significantly
      reduced the enhanced SMC expression of TNF-alpha, TNF-R1 and TNF-R2
      immunoreactivities after 24 and 48 h of organ culture. The Raf and NF-kappaB
      inhibitors significantly reduced organ culture induced TNF-alpha expression while
      they had minor effects on the TNF-alpha receptors. CONCLUSION: The present study
      shows that cerebral ischemia and organ culture induce expression of TNF-alpha and
      its receptors in the walls of cerebral arteries and that upregulation is
      transcriptionally regulated via the MEK/ERK pathway.

PMID- 21871122
TI  - Identification of sources of lead exposure in French children by lead isotope
      analysis: a cross-sectional study.
AB  - BACKGROUND: The amount of lead in the environment has decreased significantly in
      recent years, and so did exposure. However, there is no known safe exposure level
      and, therefore, the exposure of children to lead, although low, remains a major
      public health issue. With the lower levels of exposure, it is becoming more
      difficult to identify lead sources and new approaches may be required for
      preventive action. This study assessed the usefulness of lead isotope ratios for
      identifying sources of lead using data from a nationwide sample of French
      children aged from six months to six years with blood lead levels >=25 MUg/L.
      METHODS: Blood samples were taken from 125 children, representing about 600,000
      French children; environmental samples were taken from their homes and personal
      information was collected. Lead isotope ratios were determined using quadrupole
      ICP-MS (inductively coupled plasma - mass spectrometry) and the isotopic
      signatures of potential sources of exposure were matched with those of blood in
      order to identify the most likely sources. RESULTS: In addition to the
      interpretation of lead concentrations, lead isotope ratios were potentially of
      use for 57% of children aged from six months to six years with blood lead level
      >= 25 MUg/L (7% of overall children in France, about 332,000 children), with at
      least one potential source of lead and sufficiently well discriminated lead
      isotope ratios. Lead isotope ratios revealed a single suspected source of
      exposure for 32% of the subjects and were able to eliminate at least one unlikely
      source of exposure for 30% of the children. CONCLUSIONS: In France, lead isotope
      ratios could provide valuable additional information in about a third of routine
      environmental investigations.

PMID- 21871123
TI  - Evaluation of Toxoplasma gondii as a live vaccine vector in susceptible and
      resistant hosts.
AB  - BACKGROUND: Toxoplasma gondii has been shown to trigger strong cellular immune
      responses to heterologous antigens expressed by the parasite in the inbred mouse
      model. We studied the immune response induced by T. gondii as an effective
      vaccine vector in chickens and rabbits. RESULTS: T. gondii RH strain was
      engineered to express the yellow fluorescent protein (YFP) in the cytoplasm. A
      subcutaneous injection of the transgenic T. gondii YFP in chickens afforded
      partial protection against the infection of transgenic E. tenella YFP. T. gondii
      YFP induced low levels of antibodies to YFP in chickens, suggesting that YFP
      specific cellular immune response was probably responsible for the protective
      immunity against E. tenella YFP infection. The measurement of T-cell response and
      IFN-gamma production further confirmed that YFP specific Th1 mediated immune
      response was induced by T. gondii YFP in immunized chickens. The transgenic T.
      gondii stimulated significantly higher YFP specific IgG titers in rabbits than in
      chickens, suggesting greater immunogenicity in a T. gondii susceptible species
      than in a resistant species. Priming with T. gondii YFP and boosting with the
      recombinant YFP can induce a strong anti-YFP antibody response in both animal
      species. CONCLUSIONS: Our findings suggest that T. gondii can be used as an
      effective vaccine vector and future research should focus on exploring avirulent
      no cyst-forming strains of T. gondii as a live vaccine vector in animals.

PMID- 21871124
TI  - Stakeholders' perspectives on the regulation and integration of complementary and
      alternative medicine products in Lebanon: a qualitative study.
AB  - BACKGROUND: The regulation of the markets for Complementary and Alternative
      Medicine (CAM) products presents a global challenge. There is a dearth of studies
      that have examined or evaluated the regulatory policies of CAM products in the
      Eastern Mediterranean Region (EMR). We investigate the regulatory frameworks and
      the barriers for the proper regulation and integration of CAM products in
      Lebanon, as an example of an EMR country with a weak public infrastructure.
      METHODS: We utilized a qualitative study design involving a series of semi
      structured interviews with stakeholders of the CAM market in Lebanon. Snowball
      sampling was used to identify interviewees; interviews continued until the
      "saturation" point was reached. A total of 16 interviews were carried out with
      decision makers, representatives of professional associations, academic
      researchers, CAM product importers, policy makers and a media representative.
      Interviews were transcribed and thematic analysis of scripts was carried out.
      RESULTS: There was a consensus among all stakeholders that the regulation of the
      market for CAM products in Lebanon needs to be strengthened. Thematic analysis
      identified a number of impediments jeopardizing the safety of public consumption
      and hindering the integration of CAM therapies into mainstream medicine;
      including: weak infrastructure, poor regulation, ineffective policies and
      politics, weak CAM awareness and sub-optimal coordination and cooperation among
      stakeholders. With respect to policy instruments, voluntary instruments (self
      regulation) were deemed ineffective by stakeholders due to poor awareness of both
      users and providers on safe use of CAM products. Stakeholders' rather recommended
      the adoption of a combination of mixed (enhancing public awareness and
      integration of CAM into medical and nursing curricula) and compulsory (stricter
      governmental regulation) policy instruments for the regulation of the market for
      CAM products. CONCLUSIONS: The current status quo with respect to the regulation
      of CAM products in Lebanon is not conducive to public safety, nor does it support
      the integration of CAM products into the healthcare system. The Ministry of
      Health indeed plays a dominant role in the regulation of these products through a
      combination of mixed and compulsory policy instruments. Yet, the proper
      implementation of these regulations requires political resolve coupled with the
      cooperation of all CAM stakeholders.

PMID- 21871126
TI  - Proteasome modulator 9 SNPs are linked to hypertension in type 2 diabetes
      families.
AB  - BACKGROUND: Chromosome 12q24 was recently associated with hypertension.
      Proteasome Modulator 9 (PSMD9) lies in the 12q24 locus and is in linkage with
      MODY3, type 2 diabetes (T2D), microvascular and macrovascular pathology, carpal
      tunnel syndrome, and hypercholesterolemia in Italian families. AIMS: Our goal was
      to determine whether PSMD9 is linked to elevated blood pressure/hypertension in
      T2D families. METHODS: We characterized the Italian T2D families' members for
      presence and/or absence of elevated blood pressure (>= 130/80) and/or
      hypertension. The phenotypes were described as unknown in all cases in which the
      diagnosis was either unclear or the data were not available for the subject
      studied. We tested in the 200 Italians families for the presence of the linkage
      of the PSMD9 T2D risk single nucleotide polymorphisms (SNPs) IVS3+nt460 A > G,
      IVS3+nt437 T > C and E197G A > G with elevated blood pressure/hypertension. The
      non-parametric linkage analysis was performed for this qualitative phenotype by
      using the Merlin software; the Lod score and correspondent P-value were
      calculated. Parametric linkage analysis was also performed. For the significant
      linkage score, 1000 replicates were run to calculate the empirical P-value.
      RESULTS: The PSMD9 gene SNPs studied are in linkage with elevated blood
      pressure/hypertension in our Italian families. CONCLUSIONS: We conclude that the
      PSMD9 gene and/or any variant in linkage disequilibrium with the SNPs studied
      contribute to the linkage to hypertension within our family dataset. This is the
      first report of PSMD9 linkage to hypertension within the 12q24 locus.

PMID- 21871125
TI  - Safety of higher dosages of Viscum album L. in animals and humans--systematic
      review of immune changes and safety parameters.
AB  - BACKGROUND: Viscum album L extracts (VAE, mistletoe) and isolated mistletoe
      lectins (ML) have immunostimulating properties and a strong dose-dependent
      cytotoxic activity. They are frequently used in complementary cancer treatment,
      mainly to improve quality of life, but partly also to influence tumour growth,
      especially by injecting VAE locally and in high dosage. The question is raised
      whether these higher dosages can induce any harm or immunosuppressive effects.
      METHODS: Systematic review of all experiments and clinical studies investigating
      higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans
      corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune
      parameters or infections or adverse drug reactions. RESULTS: 69 clinical studies
      and 48 animal experiments reported application of higher doses of VAE or ML and
      had assessed immune changes and/or harm. In these studies, Viscum album was
      applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was
      applied up to 6.4 MUg/kg in humans and in animals up to 14 MUg/kg subcutaneously,
      50 MUg/kg nasally and 500 MUg/kg orally. A variety of immune parameters showed
      fluctuating or rising outcomes, but no immunosuppressive effect. Side effects
      consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local
      reactions at the injection site and various mild unspecific effects.
      Occasionally, allergic reactions were reported. After application of high doses
      of recombinant ML, reversible hepatotoxicity was observed in some cases.
      CONCLUSIONS: Application of higher dosages of VAE or ML is not accompanied by
      immunosuppression; altogether VAE seems to exhibit low risk but should be
      monitored by clinicians when applied in high dosages.

PMID- 21871127
TI  - The model of rat lipid metabolism disorder induced by chronic stress accompanying
      high-fat-diet.
AB  - OBJECTIVE: To develop an animal model of Lipid Metabolism Disorder, which
      conforms to human clinical characteristic. METHODS: There were 24 male Wistar
      rats that were randomly divided into 3 groups with 8 rats in each. They were
      group A (normal diet), group B (high-fat-diet), group C (chronic stress+ high-fat
      diet). Group A was fed with normal diet, while group B and C were fed with high
      fat-diet, going on for 55 days. From the 35th day, group B and C received one
      time of daily chronic stress, going on for 21 days. After that, the activities of
      the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
      and the levels of the serum triglyceride (TG), Cholesterol (Ch), high-density
      lipoprotein-Cholesterol (HDL-C) and liver TG were evaluated. RESULTS: Compared
      with group A, the activities of the serum ALT and AST, and the levels of the
      serum CH, TG, HDL-C and liver TG were found to be markedly increased, when the
      level of HDL-C was markedly decreased in group B and C, and the results of group
      C was more obviously. CONCLUSION: Chronic stress and high-fat-diet have the
      synergistic action in rat's Lipid Metabolism Disorder. They lead to a model of
      Lipid Metabolism Disorder, which conforms to human clinical characteristic much
      better.

PMID- 21871128
TI  - Great inclination to smoke among younger adults coming from low-socioeconomic
      class in Thailand.
AB  - BACKGROUND: WHO estimates that 8.4 million deaths will be counted a year due to
      tobacco by 2020, and 70% of those deaths will occur in developing countries.
      Examination of the magnitude of socioeconomic differences in smoking between
      different age groups reveals specific groups anti-smoking programs should target
      on. This study aimed to measure socioeconomic gradients related inequality in
      smoking behavior among young and old Thai male population, where general progress
      in reduction on smoking prevalence has already shown. METHODS: Data of Thai males
      aged 21 years and older from Health and Welfare Survey and Socio-Economic Survey,
      Thailand, 2006 were used in the analyses. Variables in education, household
      income, age, marital status, and region of residence were used to examine their
      associations with smoking status. RESULTS: Of the 12,200 respondents, overall
      prevalence of smoking among males aged 21 years and older was 41.5%. Lower
      education was strongly associated with smoking (OR 3.15; 95% CI, 2.74-3.62).
      Youngest age, reside in South region and lowest income were more associated with
      smoking (OR = 2.66, 1.30, and 1.91, p < 0.05, respectively). Smoking among young
      adults (age 21-30) (OR = 5.88; 95% CI, 4.3-8.0) showed stronger gradients with
      educational level than that among older adults (OR = 3.96; 95% CI, 2.8-5.3).
      CONCLUSIONS: The inverse associations between smoking prevalence and
      socioeconomic status among the Thai adult male population were consistently
      confirmed. The social gradient in smoking was greater among young adult males
      than that among older adult males.

PMID- 21871129
TI  - Younger age as a prognostic indicator in breast cancer: a cohort study.
AB  - BACKGROUND: The debate continues as to whether younger women who present with
      breast cancer have a more aggressive form of disease and a worse prognosis. The
      objectives of this study were to determine the incidence of breast cancer in
      women under 40 years old and to analyse the clinicopathological characteristics
      and outcome compared to an older patient cohort. METHODS: Data was acquired from
      a review of charts and the prospectively reviewed GUH Department of Surgery
      database. Included in the study were 276 women diagnosed with breast cancer under
      the age of forty and 2869 women over forty. For survival analysis each women less
      than 40 was matched with two women over forty for both disease stage and grade.
      RESULTS: The proportion of women diagnosed with breast cancer under the age of
      forty in our cohort was 8.8%. In comparison to their older counterparts, those
      under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower
      incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p
      < 0.001) and higher HER2 over-expression (p = 0.002); there was no statistical
      difference as regards tumour size (p = 0.477). There was no significant
      difference in overall survival (OS) for both groups; and factors like tumour size
      (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p =
      0.031) and HER2 (p = 0.002) status and treatment received were independent
      predictors of OS CONCLUSION: Breast cancer in younger women has distinct
      histopathological characteristics; however, this does not result in a reduced
      survival in this population.

PMID- 21871130
TI  - Working toward decreasing infant mortality in developing countries through change
      in the medical curriculum.
AB  - BACKGROUND: High infant and maternal mortality rates are one of the biggest
      health issues in Pakistan. Although these rates are given high priority at the
      national level (Millennium Development Goals 4 and 5, respectively), there has
      been no significant decrease in them so far. We hypothesize that this lack of
      success is because the undergraduate curriculum in Pakistan does not match local
      needs. Currently, the Pakistani medical curriculum deals with issues in maternal
      and child morbidity and mortality according to Western textbooks. Moreover, these
      are taught disjointedly through various departments. We undertook curriculum
      revision to sensitize medical students to maternal and infant mortality issues
      important in the Pakistani context and educate them about ways to reduce the same
      through an integrated teaching approach. METHODS: The major determinants of
      infant mortality in underdeveloped countries were identified through a literature
      review covering international research produced over the last 10 years and the
      Pakistan Demographic Health Survey 2006-07. An interdisciplinary maternal and
      child health module team was created by the Medical Education Department at Shifa
      College of Medicine. The curriculum was developed based on the role of identified
      determinants in infant and maternal mortality. It was delivered by an integrated
      team without any subject boundaries. Students' knowledge, skills, and attitudes
      were assessed by multiple modalities and the module itself by student feedback
      using questionnaires and focus group discussions. RESULTS: Assessment and
      feedback demonstrated that the students had developed a thorough understanding of
      the complexity of factors that contribute to infant mortality. Students also
      demonstrated knowledge and skill in counseling, antenatal care, and care of
      newborns and infants. CONCLUSIONS: A carefully designed integrated curriculum can
      help sensitize undergraduate medical students and equip them to identify and
      address complex issues related to maternal and infant mortality in underdeveloped
      countries.

PMID- 21871131
TI  - Mapping of ESE-1 subdomains required to initiate mammary epithelial cell
      transformation via a cytoplasmic mechanism.
AB  - BACKGROUND: The ETS family transcription factor ESE-1 is often overexpressed in
      human breast cancer. ESE-1 initiates transformation of MCF-12A cells via a non
      transcriptional, cytoplasmic process that is mediated by a unique 40-amino acid
      serine and aspartic acid rich (SAR) subdomain, whereas, ESE-1's nuclear
      transcriptional property is required to maintain the transformed phenotype of
      MCF7, ZR-75-1 and T47D breast cancer cells. RESULTS: To map the minimal
      functional nuclear localization (NLS) and nuclear export (NES) signals, we fused
      in-frame putative NLS and NES motifs between GFP and the SAR domain. Using these
      GFP constructs as reporters of subcellular localization, we mapped a single NLS
      to six basic amino acids (242 HGKRRR 247) in the AT-hook and two CRM1-dependent
      NES motifs, one to the pointed domain (NES1: 102 LCNCALEELRL 112) and another to
      the DNA binding domain (DBD), (NES2: 275 LWEFIRDILI 284). Moreover, analysis of a
      putative NLS located in the DBD (316 GQKKKNSN 323) by a similar GFP-SAR reporter
      or by internal deletion of the DBD, revealed this sequence to lack NLS activity.
      To assess the role of NES2 in regulating ESE-1 subcellular localization and
      subsequent transformation potency, we site-specifically mutagenized NES2, within
      full-length GFP-ESE-1 and GFP-NES2-SAR reporter constructs. These studies show
      that site-specific mutation of NES2 completely abrogates ESE-1 transforming
      activity. Furthermore, we show that exclusive cytoplasmic targeting of the SAR
      domain is sufficient to initiate transformation, and we report that an intact SAR
      domain is required, since block mutagenesis reveals that an intact SAR domain is
      necessary to maintain its full transforming potency. Finally, using a monoclonal
      antibody targeting the SAR domain, we demonstrate that the SAR domain contains a
      region accessible for protein - protein interactions. CONCLUSIONS: These data
      highlight that ESE-1 contains NLS and NES signals that play a critical role in
      regulating its subcellular localization and function, and that an intact SAR
      domain mediates MEC transformation exclusively in the cytoplasm, via a novel
      nontranscriptional mechanism, whereby the SAR motif is accessible for ligand
      and/or protein interactions. These findings are significant, since they provide
      novel molecular insights into the functions of ETS transcription factors in
      mammary cell transformation.

PMID- 21871132
TI  - Implementation and evaluation of a multisite drug usage evaluation program across
      Australian hospitals - a quality improvement initiative.
AB  - BACKGROUND: With the use of medicines being a broad and extensive part of health
      management, mechanisms to ensure quality use of medicines are essential. Drug
      usage evaluation (DUE) is an evidence-based quality improvement methodology,
      designed to improve the quality, safety and cost-effectiveness of drug use. The
      purpose of this paper is to describe a national DUE methodology used to improve
      health care delivery across the continuum through multi-faceted intervention
      involving audit and feedback, academic detailing and system change, and a
      qualitative assessment of the methodology, as illustrated by the Acute
      Postoperative Pain Management (APOP) project. METHODS: An established
      methodology, consisting of a baseline audit of inpatient medical records,
      structured patient interviews and general practitioner surveys, followed by an
      educational intervention and follow-up audit, is used. Australian hospitals,
      including private, public, metropolitan and regional, are invited to participate
      on a voluntary basis. De-identified data collected by hospitals are collated and
      evaluated nationally to provide descriptive comparative analyses. Hospitals
      benchmark their practices against state and national results to facilitate
      change. The educational intervention consists of academic detailing, group
      education, audit and feedback, point-of-prescribing prompts and system changes. A
      repeat data collection is undertaken to assess changes in practice.An online
      qualitative survey was undertaken to evaluate the APOP program. Qualitative
      assessment of hospitals' perceptions of the effectiveness of the overall DUE
      methodology and changes in procedure/prescribing/policy/clinical practice which
      resulted from participation were elicited. RESULTS: 62 hospitals participated in
      the APOP project. Among 23 respondents to the evaluation survey, 18 (78%)
      reported improvements in the documentation of pain scores at their hospital. 15
      (65%) strongly agreed or agreed that participation in APOP directly resulted in
      increased prescribing of multimodal analgesia for pain relief in postoperative
      patients. CONCLUSIONS: This national DUE program has facilitated the engagement
      and participation of a number of acute health care facilities to address issues
      relating to quality use of medicine. This approach has been perceived to be
      effective in helping them achieve improvements in patient care.

PMID- 21871133
TI  - Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma
      cells through targeting the trinity of CK2, Cdc37 and Hsp90.
AB  - BACKGROUND: Multiple myeloma (MM) is a B-cell malignancy that is largely
      incurable and is characterized by the accumulation of malignant plasma cells in
      the bone marrow. Apigenin, a common flavonoid, has been reported to suppress
      proliferation in a wide variety of solid tumors and hematological cancers;
      however its mechanism is not well understood and its effect on MM cells has not
      been determined. RESULTS: In this study, we investigated the effects of apigenin
      on MM cell lines and on primary MM cells. Cell viability assays demonstrated that
      apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells
      but not against normal peripheral blood mononuclear cells. Together, kinase
      assays, immunoprecipitation and western blot analysis showed that apigenin
      inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated
      the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase
      clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases,
      apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT
      and NF-kappaB. The treatment also downregulated the expression of the
      antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately
      induced apoptosis in MM cells. In addition, apigenin had a greater effects in
      depleting Hsp90 clients when used in combination with the Hsp90 inhibitor
      geldanamycin and the histone deacetylase inhibitor vorinostat. CONCLUSIONS: Our
      results suggest that the primary mechanisms by which apigenin kill MM cells is by
      targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the
      therapeutic potential of apigenin in treating multiple myeloma.

PMID- 21871134
TI  - Tissue inhibitor of metalloproteinases-3 mediates the death of immature
      oligodendrocytes via TNF-alpha/TACE in focal cerebral ischemia in mice.
AB  - BACKGROUND AND PURPOSE: Oligodendrocyte (OL) death is important in focal cerebral
      ischemia. TIMP-3 promotes apoptosis in ischemic neurons by inhibiting proteolysis
      of TNF-alpha superfamily of death receptors. Since OLs undergo apoptosis during
      ischemia, we hypothesized that TIMP-3 contributes to OL death. METHODS: Middle
      cerebral artery occlusion (MCAO) was induced in Timp-3 knockout (KO) and wild
      type (WT) mice with 24 or 72 h of reperfusion. Cell death in white matter was
      investigated by stereology and TUNEL. Mature or immature OLs were identified
      using antibodies against glutathione S-transferase-pi (GST-pi) and
      galactocerebroside (GalC), respectively. Expression and level of proteins were
      examined using immunohistochemistry and immunoblotting. Protein activities were
      determined using a FRET peptide. RESULTS: Loss of OL-like cells was detected at
      72 h only in WT ischemic white matter where TUNEL showed greater cell death. TIMP
      3 expression was increased in WT reactive astrocytes. GST-pi was reduced in
      ischemic white matter of WT mice compared with WT shams with no difference
      between KO and WT at 72 h. GalC level was significantly increased in both KO and
      WT ischemic white matter at 72 h. However, the increase in GalC in KO mice was
      significantly higher than WT; most TUNEL-positive cells in ischemic white matter
      expressed GalC, suggesting TIMP-3 deficiency protects the immature OLs from
      apoptosis. There were significantly higher levels of cleaved caspase-3 at 72 h in
      WT white matter than in KO. Greater expression of MMP-3 and -9 was seen in
      reactive astrocytes and/or microglia/macrophages in WT at 72 h. We found more
      microglia/macrophages in WT than in KO, which were the predominant source of
      increased TNF-alpha detected in the ischemic white matter. TACE activity was
      significantly increased in ischemic WT white matter, which was expressed in
      active microglia/macrophages and OLs. CONCLUSIONS: Our results suggested that
      focal ischemia leads to proliferation of immature OLs in white matter and that
      TIMP-3 contributes to a caspase-3-dependent immature OL death via TNF-alpha
      mediated neuroinflammation. Future studies will be needed to delineate the role
      of MMP-3 and MMP-9 that were increased in the Timp-3 wild type.

PMID- 21871135
TI  - Does human bocavirus infection depend on helper viruses? A challenging case
      report.
AB  - A case of severe diarrhoea associated with synergistic human bocavirus type 1
      (HBoV) and human herpes virus type 6 (HHV6) is reported. The case supports the
      hypotheses that HBoV infection under clinical conditions may depend on helper
      viruses, or that HBoV replicates by a mechanism that is atypical for
      parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

PMID- 21871136
TI  - Benign prostatic hyperplasia and male lower urinary tract symptoms (LUTS).
AB  - INTRODUCTION: Lower urinary tract symptoms related to benign prostatic
      hyperplasia (BPH) and bladder outlet obstruction may affect up to 30% of men in
      their early 70s. Symptoms can improve without treatment, but the usual course is
      a slow progression of symptoms, with acute urinary retention occurring in 1% to
      2% of men with BPH per year. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical questions: What are the effects
      of medical, herbal, and surgical treatments? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to July 2009 (Clinical
      Evidence reviews are updated periodically, please check our website for the most
      up-to-date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 63
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: 5 alpha
      reductase inhibitors, alpha-blockers, beta-sitosterol plant extract, Pygeum
      africanum, rye grass pollen extract, saw palmetto plant extracts, transurethral
      electrovaporisation, transurethral Holmium laser enucleation of the prostate,
      transurethral microwave thermotherapy, transurethral needle ablation, and
      transurethral resection (including transurethral resection versus transurethral
      incision, and transurethral resection versus visual laser ablation/laser
      vaporisation).

PMID- 21871137
TI  - Diabetes: foot ulcers and amputations.
AB  - INTRODUCTION: Diabetic foot ulceration is full-thickness penetration of the
      dermis of the foot in a person with diabetes. Severity is classified using the
      Wagner system, which grades it from 1 to 5. The annual incidence of ulcers among
      people with diabetes is 2.5% to 10.7% in resource-rich countries, and the annual
      incidence of amputation for any reason is 0.25% to 1.8%. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of interventions to prevent foot ulcers and
      amputations in people with diabetes? What are the effects of treatments in people
      with diabetes with foot ulceration? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to September 2010 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 50
      systematic reviews and RCTs that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: debridement, human cultured dermis, human
      skin equivalent, patient education, pressure off-loading with felted foam or
      pressure-relief half-shoe, pressure off-loading with total-contact or non
      removable casts, screening and referral to foot-care clinics, systemic hyperbaric
      oxygen for non-infected ulcers, systemic hyperbaric oxygen in infected ulcers,
      therapeutic footwear, topical growth factors, and wound dressings.

PMID- 21871138
TI  - [An elderly woman with abdominal pain].
AB  - A 89-year-old woman came to the hospital with abdominal pain, vomiting and
      melaena. A CT-scan showed the complaints were caused by a hernia obturatoria
      incarcerata. After surgery the woman recovered uneventfully.

PMID- 21871139
TI  - [Diagnosis and treatment of rotator cuff tears].
AB  - A rotator cuff tear is a highly prevalent disorder, occurring in 25% of people
      over 60 years of age. In two thirds of patients the tear is small and
      asymptomatic. Acute, symptomatic cuff tears may occur in active sportsmen and
      women aged 30-50. There is often a considerable delay in diagnosis in this group,
      due to a lack of recognition by either the patient or the doctor. Recently
      identified risk factors for the development of cuff tear are nicotine abuse,
      hypercholesterolaemia, contralateral cuff tear and genetic predisposition.
      Conservative treatment can be very successful and consists of physical therapy
      and effective analgesics. Repeated steroid injections are harmful to the
      tendinous tissue and should be avoided. The aim of surgery is anatomical
      reinsertion of the ruptured tendon using an open or arthroscopic procedure. The
      arthroscopic procedure enables the surgeon to perform a more extensive evaluation
      and treatment of the joint. The arthroscopic procedure is technically more
      demanding than the open procedure, but seems to have a shorter rehabilitation
      period.

PMID- 21871140
TI  - [Corneal crosslinking as treatment for progressive keratoconus].
AB  - Corneal crosslinking (CXL) is a relatively new medical treatment for progressive
      cases of keratoconus. This disease is characterized by corneal deformation and
      thinning, leading to corneal surface distortion and visual disability, mainly
      occurring in young patients. CXL was first applied in humans in 1999 and is
      internationally considered the standard treatment for cases of rapidly
      progressing keratoconus. The treatment protocol consists of corneal epithelial
      removal, the administration of riboflavin eye drops and irradiation with
      ultraviolet-A light. The primary goal of CXL is to mechanically stabilize and
      strengthen the cornea. CXL plays an important role in the treatment of
      keratoconus and may in the future delay or eliminate the need for a corneal
      transplantation.

PMID- 21871141
TI  - [Myocardial infarction in a 16-year old following inhalation of butane gas].
AB  - BACKGROUND: Butane gas is inhaled by young people with the aim of getting 'high'.
      This can cause coronary spasm with myocardial infarction and ventricular
      fibrillation as a result. CASE DESCRIPTION: We report on a 16-year-old male who
      collapsed at home after sniffing butane. His father, together with a paramedical
      emergency team that had found ventricular fibrillation, started basic and
      advanced life support. ECG showed exaggerated ST-elevations and an
      echocardiography showed a hypokinetic anterior ventricular wall and ventricular
      septum. After treatment with dobutamine, nitroglycerine, acetylsalicylic acid and
      dalteparine, the ECG and left ventricular function improved. He was admitted to a
      pediatric intensive care unit where he was artificially ventilated for 4 days and
      treated for cardiogenic shock. In the following days his cardiovascular condition
      improved. Magnetic resonance imaging showed no ischaemic damage of the brain. At
      6 weeks his general condition was not as before, but ECG and cardiac function had
      almost recovered. CONCLUSION: Young people who experiment with inhalation of
      volatile substances generally do not know how dangerous this is. Provision of
      information about the possible consequences will have a preventive effect.

PMID- 21871142
TI  - Composition, indigenous proteolytic enzymes and coagulating behaviour of ewe milk
      as affected by somatic cell count.
AB  - This study was undertaken to assess the effect of somatic cell count in ewe milk
      on i) composition and hygienic traits; ii) plasmin, cathepsin and elastase
      activities; iii) leukocyte differential count; iv) renneting parameters.
      Individual ewe milk samples were grouped according to somatic cell count (SCC)
      into five classes: SC300 (<300 000 cells/ml), SC500 (from 301 000 to 500 000
      cells/ml), SC1000 (from 501 000 to 1 000 000 cells/ml), SC2000 (from 1 001 000 to
      2 000 000 cells/ml) and SC>2000 (>2 001 000 cells/ml). Individual milk samples
      were analysed for pH, chemical composition, microbial features, indigenous
      proteolytic enzymes, differential leukocyte population, and renneting parameters.
      Milk yield, lactose, protein, non casein nitrogen, microbial features were
      affected by SCC level. Plasmin and elastase activities were the highest in
      samples with more than 1 000 000 cells/ml; plasmin had intermediate values in
      samples with 300 000 to 1 000 000 cells/ml and the lowest in samples with less
      than 300 000 cells/ml of milk. Cathepsin D showed significantly lower values in
      SC300 and SC1000 classes than in SC500, SC2000 and SC>2000 classes. The highest
      percentages of lymphocyte were found in samples with less than 1 000 000
      cells/ml, while the highest levels of polymorphonuclear leukocyte were found in
      samples with more than 1 000 000 cells/ml of milk. Longer clotting time was found
      in SC>2000 samples, while reduced clot firmness was observed in SC500 and SC>2000
      samples. Results on milk yield and on compositional parameters evidenced an
      impairment of udder efficiency in ewe milk samples starting from 300 000
      cells/ml. Plasmin activity in milk can be considered as a marker of the synthetic
      and secreting ability of the mammary gland; furthermore plasmin and elastase were
      consistent with the health status of the udder. Finally cathepsin D played a role
      in the worsening of renneting properties of ewe milk.

PMID- 21871143
TI  - Age-related decline in macrophage and lymphocyte functions in mice and its
      alleviation by treatment with probiotic Dahi containing Lactobacillus acidophilus
      and Bifidobacterium bifidum.
AB  - This study evaluated the effects of probiotic Dahi administration in ageing mice
      on macrophage and lymphocyte functions. Probiotic Dahi were prepared by co
      culturing in buffalo milk (3% fat) Dahi bacteria (Lactococcus lactis ssp.
      cremoris NCDC-86 and Lc. lactis ssp. lactis biovar diacetylactis NCDC-60) along
      with Lactobacillus acidophilus LaVK2 (La-Dahi) or combined Lb. acidophilus and
      Bifidobacterium bifidum BbVK3 (LaBb-Dahi). Four groups of 12 mo old mice were fed
      for four months, with the supplements (5 g/day) of buffalo milk (3% fat), Dahi,
      La-Dahi and LaBb-Dahi, respectively, in addition to basal diet, and a fifth group
      that received no supplements served as control. The immune functions of young
      mice (4 mo old) were also compared with those of ageing adult mice (16 mo old).
      The production of nitric oxide and cytokines IL-6 and TNF-alpha declined and that
      of immunosuppressive prostaglandin E2 (PGE2) increased by stimulated peritoneal
      and splenic macrophages in ageing mice, compared with their young counterparts.
      The proliferation of stimulated splenocytes diminished and the production of IL-2
      decreased and that of IL-6 and TNF-alpha enhanced in ageing compared with young
      mice. Feeding ageing mice with La-Dahi or LaBb-Dahi improved peritoneal
      macrophage functions stimulating nitric oxide and IL-6 and diminishing PGE2
      production. Feeding La-Dahi or LaBb-Dahi also improved lymphocyte functions
      stimulating their proliferation and production of IL-2 in ageing mice. To
      conclude, the probiotic La-Dahi and LaBb-Dahi are effective in reversing age
      related decline in immune functions in mice.

PMID- 21871144
TI  - Probiotic lactobacilli and bifidobacteria in a fermented milk product with added
      fruit preparation reduce antibiotic associated diarrhea and Helicobacter pylori
      activity.
AB  - To investigate matrix-specifity of probiotic effects and particularly of the
      reduction of antibiotics-associated diarrhea, a controlled, randomized, double
      blind study was performed, in which 88 Helicobacter pylori-infected but otherwise
      healthy subjects were given for eight weeks either a) a probiotic fruit yoghurt
      "mild" containing Lactobacillus acidophilus LA-5 plus Bifidobacterium lactis BB
      12, n = 30), b) the same product but pasteurized after fermentation (n = 29) or
      c) milk acidified with lactic acid (control, n = 29). During week five, a
      Helicobacter eradication therapy was performed. Helicobacter activity was
      measured via 13C-2-urea breath tests and antibiotic-associated diarrhoea and
      other gastrointestinal complaints were recorded by validated questionnaires. In
      intervention group a, b and c the mean number of days with diarrhoea was 4, 10
      and 10 (P<0.05), the frequency of episodes 17%, 7% and 27% (n.s.), and the change
      in total symptoms score before antibiotics treatment was -1.4 +/- 1.1, -1.2 +/-
      1.1, 2.6 +/- 1.1 points/four weeks (P<0.05). All milk products decreased
      Helicobacter activity by 18 to 45% without significant differences between
      groups. The observed decrease in Hel. pylori activity seems to be not or not only
      due to probiotic bacteria but (rather) to components of acidified milk (most
      probably lactic acid). Fruit-yogurt-like fermented milk products with living
      probiotic bacteria significantly shorten the duration of antibiotics-associated
      diarrhoea and improve gastrointestinal complaints. Fruit yogurt-like fermented
      milk is a matrix suitable for probiotic bacteria.

PMID- 21871145
TI  - Tactile picture recognition: errors are in shape acquistion or object matching?
AB  - Numerous studies have demonstrated that sighted and blind individuals find it
      difficult to recognize tactile pictures of common objects. However, it is still
      not clear what makes recognition of tactile pictures so difficult. One
      possibility is that observers have difficulty acquiring the global shape of the
      image when feeling it. Alternatively, observers may have an accurate
      understanding of the shape but are unable to link it to a particular object
      representation. We, therefore, conducted two experiments to determine where
      tactile picture recognition goes awry. In Experiment 1, we found that recognition
      of tactile pictures by blindfolded sighted observers correlated with image
      characteristics that affect shape acquisition (symmetry and complexity). In
      Experiment 2, we asked drawing experts to draw what they perceived after feeling
      the images. We found that the experts produced three types of drawings when they
      could not recognize the tactile pictures: (1) drawings that did not look like
      objects (incoherent), (2) drawings that looked like incorrect objects (coherent
      but inaccurate) and (3) drawings that looked like the correct objects ( coherent
      and accurate). The majority of errors seemed to result from inaccurate perception
      of the global shape of the image (error types 1 and 2). Our results suggest that
      recognition of simplistic tactile pictures of objects is largely inhibited by low
      level tactile shape processing rather than high-level object recognition
      mechanisms.

PMID- 21871146
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method for the identification and quantification of JWH-018, JWH-073, JWH-019,
      and JWH-250 in human whole blood.
AB  - A sensitive and specific method for the quantification of JWH-018, JWH-073, and
      JWH-250 and the qualitative identification of JWH-019 in whole blood was
      developed and validated. Samples fortified with JWH-018-d9 and JWH-073-d9
      underwent liquid-liquid extraction and were analyzed by liquid chromatography
      positive ion electrospray ionization-tandem mass spectrometry. Two transitions
      were monitored for all analytes except JWH-250, for which there was only one
      available transition. JWH-019 did not meet the stringent requirements for
      quantitative analysis, and thus this method is only appropriate for the
      qualitative identification of this compound in whole blood. The linear range was
      0.1-20 MUg/L for all quantitative analytes. The maximum average within and
      between-run imprecision was 7.9% and 10.2%, respectively, and all controls
      quantified within 8.2% of target concentrations. Process efficiency, a
      measurement that takes into effect extraction efficiency and matrix effect, was
      >= 32.0% for all quantitative analytes; similar results were obtained for the
      deuterated internal standards. All analytes were stable at room, refrigerated,
      and frozen temperatures for at least 30 days. The method was used to quantify JWH
      018 and JWH-073 in a blood specimen collected from a person known to have used an
      herbal incense blend containing these substances.

PMID- 21871147
TI  - Cannabinoids in postmortem toxicology.
AB  - Cannabinoids are often excluded from postmortem toxicology screens due to their
      ubiquitous nature, interpretative difficulties and unanswered questions regarding
      their postmortem redistribution. In this study, we review 30 postmortem cases
      where a drug screen gave a positive cannabinoids result and a confirmation
      identified Delta9-tetrahydrocannabinol (THC), 11-hydroxy-Delta9
      tetrahydrocannabinol (11-OH-THC), and/or 11-nor-9-carboxy-Delta9
      tetrahydrocannabinol (THC-COOH) in peripheral (BL-P) or cardiac/central blood (BL
      C) and/or urine (UR). Had cannabinoids not been included in these toxicologic
      evaluations, incomplete or erroneous inferences would have been drawn in a
      substantial number of cases regarding cause/manner of death. THC was detected in
      28 BL-C and in all 30 BL-P. THC and THC-COOH were confirmed present in 2 and 23
      UR, respectively. 11-OH-THC was detected in 4 BL-C, 6 BL-P, and 0 UR. The mean
      THC concentrations in BL-C and BL-P were 8.0 and 15.8 ng/mL, respectively. The
      mean THC-COOH concentrations in BL-C and BL-P were 55.2 and 60.6 ng/mL,
      respectively. The mean 11-OH-THC concentrations in BL-C and BL-P were 17.0 and
      12.5 ng/mL, respectively. Postmortem interval (PMI) for each case was determined
      and evaluated in relation to BL-C/BL-P concentration ratios with THC-COOH
      exhibiting a possible trend. This study is the first of its kind and demonstrates
      the usefulness of cannabinoid analyses as part of death investigations.
      Furthermore, it provides distribution data that will improve the ability of
      toxicologists and pathologists to evaluate cannabinoid concentrations in human
      postmortem specimens.

PMID- 21871148
TI  - Calculation and verification of blood ethanol measurement uncertainty for
      headspace gas chromatography.
AB  - An estimate was made of the measurement uncertainty for blood ethanol testing by
      headspace gas chromatography. While uncertainty often focuses on compliance to a
      single threshold level (0.08 g/100 mL), the existence of multiple thresholds,
      related to enhanced sentencing, subject age, or commercial vehicle licensure,
      necessitate the use of an estimate with validity across multiple specification
      levels. The uncertainty sources, in order of decreasing magnitude, were method
      reproducibility, linear calibration, recovery, calibrator preparation, reference
      material, and sample preparation. A large set of reproducibility data was
      evaluated (n = 15,433) in order to encompass measurement variability across
      multiple conditions, operators, instruments, concentrations and timeframes. The
      relative, combined standard uncertainty was calculated as +/-2.7%, with an
      expanded uncertainty of +/-8.2% (99.7% level of confidence, k = 3). Bias was
      separately evaluated through a recovery study using standard reference material
      from a national metrology institute. The uncertainty estimate was verified
      through the use of proficiency test (PT) results. Assigned values for PT results
      and their associated uncertainties were calculated as robust means (x*) and
      standard deviations (s*) of participant values. Performance scores demonstrated
      that the uncertainty estimate was appropriate across the full range of PT
      concentrations (0.010-0.370 g/100 mL). The use of PT data as an empirical
      estimate of uncertainty was not examined. Until providers of blood ethanol PT
      samples include details on how an assigned value is obtained along with its
      uncertainty and traceability, the use of PT data should be restricted to the role
      of verification of uncertainty estimates.

PMID- 21871149
TI  - Postmortem drug screening by non-targeted and targeted ultra-performance liquid
      chromatography-mass spectrometry technology.
AB  - In the medical examiner setting, comprehensive drug screening is an essential
      analytical tool in the investigation of cause and manner of death.We have
      validated non-targeted and targeted screening assays for drugs and metabolites
      using ultra-performance liquid chromatography (UPLC) interfaced with mass
      spectrometry (MS) in single and tandem stages. For non-targeted screening by UPLC
      MS electrospray interface, in-source fragmentation was used along with MS
      scanning (m/z 80-650) and library search for over 700 drug and metabolite
      analytes. Targeted detection of over 200 analytes by UPLC-MS-MS was performed
      with dual transition ion monitoring. Validation studies confirmed reproducibility
      of both mass spectra produced by in-source fragmentation and transition ion
      ratios by collision-cell dissociation. Lower limit of detection by UPLC-MS (10
      150 ng/mL) and UPLC-MS-MS (1-50 ng/mL) was determined for a subset of drugs and
      correlated with extraction recovery and matrix effect. Drug findings by UPLC-MS
      and UPLC- MS-MS were compared with gas chromatography-mass spectrometry (GC-MS)
      screening in postmortem blood from 410 medical examiner cases with 1121 positive
      drug findings by all methods. Accuracy, based on results of confirmation testing,
      was high (98-99%) across all screening assays and detection sensitivity by GC-MS
      (71%), UPLC-MS (73%), and UPLC-MS-MS (76%) was determined. UPLC-MS plus UPLC-MS
      MS screening resulted in the highest drug detection rate (95%) and provided
      optimal dual-screening for the postmortem casework.

PMID- 21871150
TI  - Synthetic cannabinoids in oral fluid.
AB  - At the end of 2010, the U.S. Drug Enforcement Administration (DEA) used its
      emergency scheduling authority to temporarily control five chemicals, JWH-018,
      JWH-073, JWH-200, CP-47497, and cannabicyclohexanol (CP-47497 C8), often referred
      to as "Spice", K2, or "synthetic cannabinoids" because of their reported cannabis
      like effects. JWH-250 is commonly encountered, and HU-210 was already controlled,
      so these were also included in the research. We report the first analytical
      procedure for the simultaneous determination of these compounds in oral fluid
      specimens collected with the QuantisalTM device using solid-phase extraction and
      liquid chromatography with tandem mass spectrometry. The method was validated and
      applied to specimens taken from two individuals who had purchased the synthetic
      compounds while still legally available in the U.S. After a single session of
      smoking "Blueberry Posh", the peak concentration of JWH-018 detected was 35 MUg/L
      20 min after smoking; JWH-018 was still detectable 12 h after a single intake.
      After a single session of smoking "Black Mamba", JWH-018 was detected with a peak
      concentration of 5 MUg/L after 20 min. In this subject, the compound was not
      detectable after 12 h.

PMID- 21871151
TI  - Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations
      may identify drug-susceptible populations.
AB  - Methadone is used worldwide for the treatment of heroin addiction; however, fatal
      poisonings are increasingly reported. The prevalence of CYP2B6 and MU-opioid
      receptor (OPRM1) gene variations were examined between a postmortem population
      where the deaths were associated with methadone and a live nondrug-using control
      population using TaqmanTM SNP Genotyping assays. The CYP2B6*6 allele was higher
      in the postmortem population, but the difference was not significant (P = 0.92).
      The CYP2B6 T750C promoter variation was similar in frequency for both
      populations. Linkage between T750C and CYP2B6*6 was identified for both
      populations (P < 0.01). The prevalence of the OPRM1 A118G variation was
      significantly higher in the control population (P = 0.0046), which might indicate
      a protective mechanism against opioid toxicity. Individual susceptibility to
      methadone may be determined by screening for CYP2B6*6.

PMID- 21871152
TI  - Detection of various performance enhancing substances in specimens collected from
      race horses in Illinois: a five-year experience.
AB  - In order to protect the integrity of horse racing in Illinois, a complex testing
      of urine and blood specimens collected post-race from winning and special
      designation horses is continuously conducted. The initial screening by
      immunoassays was followed by the confirmation on presumptive positive samples.
      Instrumental screening was also conducted. Perimortem and postmortem specimens
      and special exhibits (syringes, needles, etc.) were also analyzed. The
      administration of alkalinizing agents was detected by measuring the total plasma
      carbon dioxide concentration. The laboratory analyzed specimens collected post
      race from winning horses and special designation horses at eight race tracks in
      the State of Illinois over the five-year time period (2004-2009). The total
      number of specimens collected was 91,808, comprising 45,210 urine specimens and
      46,598 blood specimens. The total number of violations was 413 (0.45% of the
      total number of specimens analyzed); 207 were blood specimens (0.44% of the total
      blood specimens analyzed), and 206 were urine specimens (0.45% of the total urine
      specimens analyzed). A total of 220 violations were reported for harness horses,
      and 193 were reported for Thoroughbred horses. The number of reported violations
      of the total tested specimens in Illinois was small, but a wide variety of
      performance-enhancing drugs was shown.

PMID- 21871153
TI  - Evaluation of commercial enzyme-linked immunosorbent assays to identify
      psychedelic phenethylamines.
AB  - The 2C, 2C-T, and DO series of designer drugs pose a number of challenges to
      forensic toxicology laboratories. Although these drugs are seized by law
      enforcement agencies throughout the United States, they are not readily detected
      in forensic toxicology laboratories. A systematic evaluation of the cross
      reactivity of 9 commercial enzyme-linked immunosorbent assays (ELISAs) was
      conducted using 11 designer drugs. Cross-reactivity was measured towards 2,5
      dimethoxy-4-bromophenethylamine (2C-B), 2,5-dimethoxyphenethylamine (2C-H), 2,5
      dimethoxy4-iodophenethylamine (2C-I), 2,5-dimethoxy-4ethylthiophenethylamine (2C
      T-2), 2,5-dimethoxy-4isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy
      4propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4bromoamphetamine (DOB), 2,5
      dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5
      dimethoxy-4-methylamphetamine (DOM), and 4methylthioamphetamine (4-MTA). Cross
      reactivity towards the 2C, 2C-T, and DO series of psychedelic amphetamines was <
      0.4%. Concentrations as high as 50,000 ng/mL in urine, which greatly exceed those
      expected in forensic case samples, were not sufficient to produce a positive
      result. The only substance to produce any measurable cross-reactivity was 4-MTA.
      Cross-reactivities of 5 and 7% were obtained using four methamphetamine/MDMA
      directed assays, 25 and 200% using two amphetamine-directed assays. The absence
      of any measurable cross-reactivity towards the 10 2C, 2C-T, and DO psychedelic
      phenethylamines makes it harder to detect these drugs using routine screening. As
      a consequence, laboratories that rely upon immunoassay rather than more broad
      spectrum chromatographic screening techniques, may fail to detect these powerful
      psychedelic substances.

PMID- 21871154
TI  - Relative distribution of ketamine and norketamine in skeletal tissues following
      various periods of decomposition.
AB  - Skeletal tissues (rat) were analyzed for ketamine (KET) and norketamine (NKET)
      following acute ketamine exposure (75 mg/kg i.p.) to examine the influence of
      bone type and decomposition period on drug levels. Following euthanasia, drug
      free (n = 6) and drug-positive (n = 20) animals decomposed outdoors in rural
      Ontario for 0, 1, or 2 weeks. Skeletal remains were recovered and ground samples
      of various bones underwent passive methanolic extraction and analysis by GC-MS
      after solid-phase extraction. Drug levels, expressed as mass normalized response
      ratios, were compared across tissue types and decomposition periods. Bone type
      was a main effect (p < 0.05) for drug level and drug/metabolite level ratio
      (DMLR) for all decomposition times, except for DMLR after 2 weeks of
      decomposition. Mean drug level (KET and NKET) and DMLR varied by up to 23-fold,
      18-fold, and 5-fold, respectively, between tissue types. Decomposition time was
      significantly related to DMLR, KET level, and NKET level in 3/7, 4/7, and 1/7
      tissue types, respectively. Although substantial sitedependence may exist in
      measured bone drug levels, ratios of drug and metabolite levels should be
      investigated for utility in discrimination of drug administration patterns in
      forensic work.

PMID- 21871155
TI  - Simultaneous detection of ten psychedelic phenethylamines in urine by gas
      chromatography-mass spectrometry.
AB  - Psychedelic phenethylamines are an emerging class of designer drugs capable of
      producing a complex array of sought after adrenergic and hallucinogenic effects.
      Toxicological detection poses a number of challenges to laboratories. The purpose
      of this study was to develop a procedure for the detection of psychedelic
      amphetamines using techniques that are widely accepted in forensic toxicology
      laboratories. In all, 10 target analytes were selected: 2,5-dimethoxy-4
      bromophenethylamine (2C-B), 2,5-dimethoxyphenethylamine (2C-H), 2,5-dimethoxy
      4iodophenethylamine (2C-I), 2,5-dimethoxy-4ethylthiophenethylamine (2C-T-2), 2,5
      dimethoxy-4-(n)propylthiophenethylamine (2C-T-7), 4-methylthioamphetamine (4
      MTA), 2,5-dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-ethylamphetamine
      (DOET), 2,5-dimethoxy4-iodoamphetamine (DOI), and 2,5-dimethoxy
      4methylamphetamine (DOM). Target drugs in urine were analyzed by gas
      chromatography in selected ion monitoring mode after mixed-mode solid-phase
      extraction. Limits of detection for all analytes were 2-10 ng/mL, and limits of
      quantitation were 10 ng/mL or less. Precision evaluated at 50 and 500 ng/mL
      yielded CVs of 0.4-7.9% and accuracy in the range 91-116%. Calibration curves
      were linear to 1500 ng/mL using mescaline-d9 as the internal standard. No
      carryover was evident at 5000 ng/mL (the highest concentration tested) and no
      interferences were observed from the presence of other structurally related
      compounds or endogenous bases.

PMID- 21871156
TI  - (+/-)-3,4-methylenedioxymethamphetamine and metabolite disposition in plasma and
      striatum of wild-type and multidrug resistance protein 1a knock-out mice.
AB  - Mice lacking multidrug resistance protein 1a (mdr1a) are protected from
      methylenedioxymethamphetamine (MDMA)-induced neurotoxicity, suggesting mdr1a
      might play an important role in this phenomenon. We characterized MDMA
      pharmacokinetics in murine plasma and brain to determine if mdr1a alters MDMA
      distribution. Wild-type (mdr1a+/+) and mdr1a knock-out (mdr1a-/-) mice received
      i.p. 10, 20 or 40 mg/kg MDMA. Plasma and brain specimens were collected 0.3-4 h
      after MDMA, and striatum were dissected. MDMA and metabolites were quantified in
      plasma and striatum by gas chromatography-mass spectrometry. MDMA maximum plasma
      concentrations (C(max)) for both strains were 916- 1363, 1833-3546, and 5979-7948
      MUg/L, whereas brain C(max) were 6673-14,869, 23,428-29,433, and 52,735-66,525
      MUg/kg after 10, 20, or 40 mg/kg MDMA, respectively. MDMA and metabolite
      striatum/plasma AUC ratios were similar in both strains, inconsistent with
      observed MDMA neuroprotective effects in mdr1a-/- mice. Ratios of
      methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA)
      AUCs exceeded 18% of MDMA's in plasma, suggesting substantial MDMA hepatic
      metabolism in mice. MDMA, MDA, HMMA, and 4-hydroxy-3-methoxyamphetamine maximum
      concentrations and AUCs exhibited nonlinear relationships during dose-escalation
      studies, consistent with impaired enzymatic demethylenation. Nonlinear increases
      in MDMA plasma and brain concentrations with increased MDMA dose may potentiate
      MDMA effects and toxicity.

PMID- 21871157
TI  - Evaluation of a new phencyclidine enzyme immunoassay for the detection of
      phencyclidine in urine with confirmation by high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - We present an evaluation of a new phencyclidine (PCP) enzyme immunoassay (PCPI)
      for detection in urine. The PCPI was evaluated by testing 523 urine specimens.
      Controls containing 0 ng/mL of PCP and -25% (negative control) and +25% (positive
      control) of the 25 ng/mL cutoff calibrator were analyzed with each batch. All
      urines were analyzed by high-performance liquid chromatography- tandem mass
      spectrometry (HPLC-MS-MS) for PCP. Of the 523 specimens tested, 218 yielded
      positive results by the PCP assay. HPLC-MS-MS confirmed the presence of at least
      25 ng/mL in 214 specimens, indicating four false-positive results containing 11,
      13, 16, and 20 ng/mL PCP. Three specimens yielded a negative result; however, PCP
      concentrations were within 20% of the 25 ng/mL cutoff value. The overall
      agreement of PCPI and HPLC-MS-MS results was 98.7%. The sensitivity of the PCPI
      was 0.982 and the specificity 0.987. Testing at 100 ng/mL of other drugs or their
      metabolites demonstrated no cross-reactivity. The within-run precision was CV =
      2% (n = 12); the between-run precision was CV = < 6% (n = 4). The assay was found
      linear from -50% to 150% (12.5-37.5 ng/mL) of the cutoff concentration. The Lin
      Zhi PCPI provides a precise, reliable method for the routine detection of
      phencyclidine in urine specimens.

PMID- 21871158
TI  - Liquid chromatography-tandem mass spectrometry analysis of urine specimens for K2
      (JWH-018) metabolites.
AB  - Marijuana is the most widely used drug of abuse all over the world. The major
      active constituent of the drug is Delta9- tetrahydrocannabinol (Delta9-THC).
      Delta9-THC exerts its psychological activities by interacting with the
      cannabinoid receptors (CB1 and CB2) in the brain. JWH-018, HU-210, and CP-47497,
      with CB1 agonist activity (similar to Delta9-THC), have been used by the drug
      culture to spike smokable herbal products to attain psychological effects similar
      to those obtained by smoking marijuana. The products spiked with these CB1
      agonists are commonly referred to as "Spice" or "K2". The most common compound
      used in these products is JWH-018 and related compounds (JWH-073 and JWH-250).
      Little work has been done on the detection of these synthetic cannabimimetic
      compounds in biological specimens. This report investigated the metabolism of JWH
      018 by human liver microsomes, identification of the metabolites of JWH-018 in
      urine specimen of an individual who admitted use of the drug, and reports on the
      quantitation of three of its urinary metabolites, namely the 6-OH-, the N-alkyl
      OH (terminal hydroxyl)-, and the N-alkyl terminal carboxy metabolites using
      liquid chromatography-tandem mass spectrometry. The concentrations of these
      metabolites are determined in several forensic urine specimens.

PMID- 21871159
TI  - Cannabichromene and tetrahydrocannabinol determination in mouse blood and brain
      by gas chromatography-mass spectrometry.
AB  - Cannabichromene (CBC) is a phytocannabinoid, the second most abundant cannabinoid
      quantitatively in marijuana. CBC has been shown to produce antinociception and
      anti-inflammatory effects in rodents. This method is validated for the
      measurement of THC and CBC simultaneously after extraction from mouse blood or
      brain. Whole brain harvested from mice was homogenized 2:1 (v/w) with normal
      saline. Fifty nanograms of THC-d3 was added to 0.5 mL of heparinized mouse blood,
      brain homogenate, and THC and CBC fortified blood or brain calibrators, then
      equilibrated overnight at 5  degrees C. Two milliliters of "ice cold"
      acetonitrile was added drop-wise while the sample was vortex mixed, and then the
      sample was centrifuged and stored overnight at -30  degrees C. The cannabinoids
      were extracted from the acetonitrile layer with 2 mL of 0.2 N NaOH and 4 mL of
      hexane/ethyl acetate (9:1). The solvent was isolated and evaporated to dryness.
      Trimethylsilyl derivatives were prepared and then analyzed by gas chromatography
      mass spectrometry. Linearity in blood and brain of THC and CBC was 2-10,000 ng/mL
      (ng/g). THC and CBC recovery ranged from 56 to 78% in blood and brain. Precision
      was demonstrated at 100 ng/mL and 1000 ng/mL with CVs < 15%. The validated method
      allows for blood and brain concentrations of cannabinoids to be quantificated and
      correlated with pharmacological effects produced in mice.

PMID- 21871160
TI  - Ethanol analysis by headspace gas chromatography with simultaneous flame
      ionization and mass spectrometry detection.
AB  - Ethanol is the most frequently identified compound in forensic toxicology.
      Although confirmation involving mass spectrometry is desirable, relatively few
      methods have been published to date. A novel technique utilizing a Dean's Switch
      to simultaneously quantitate and confirm ethyl alcohol by flame-ionization (FID)
      and mass spectrometric (MS) detection after headspace sampling and gas
      chromatographic separation is presented. Using 100 MUL of sample, the limits of
      detection and quantitation were 0.005 and 0.010 g/dL, respectively. The zero
      order linear range (r(2) > 0.990) was determined to span the concentrations of
      0.010 to 1.000 g/dL. The coefficient of variation of replicate analyses was less
      than 3.1%. Quantitative accuracy was within +/-8%, +/-6%, +/-3%, and +/-1.5% at
      concentrations of 0.010, 0.025, 0.080, and 0.300 g/dL, respectively. In addition,
      1,1-difluoroethane was validated for qualitative identification by this method.
      The validated FID-MS method provides a procedure for the quantitation of ethyl
      alcohol in blood by FID with simultaneous confirmation by MS and can also be
      utilized as an identification method for inhalants such as 1,1-difluoroethane.

PMID- 21871162
TI  - Ethanol production in a postmortem urine sample.
AB  - Significant ethanol production in a urine sample is not a common phenomenon that
      occurs in postmortem volatile anaylsis. Here, a 66-year-old female decedent with
      a history of renal failure and diabetes originally presented at the hospital as
      "acting funny". After expiring at the hospital, the toxicology section received
      both hospital and postmortem samples for analysis. Initially, only hospital blood
      and urine were analyzed for volatiles. The hospital blood was only positive for
      acetone. As a second matrix confirmation, the autopsy urine was also analyzed and
      found to be positive for acetone and ethanol. Upon initial examination, the urine
      sample had an ethanol value of 0.10 g%, which continued to increase to a peak
      concentration of 0.28 g%. This case study focuses on the production of ethanol in
      a urine sample that was analyzed over a three-month period. Also presented is a
      vitreous humor metabolic panel that contains glucose, creatinine, and urea
      nitrogen data for this case.

PMID- 21871161
TI  - A fatality due to an accidental methadone substitution in a dental cocktail.
AB  - A 6-year-old male child was scheduled for a dental procedure requiring conscious
      sedation. Prior to the procedure, the child was administered a dental cocktail
      containing chloral hydrate, hydroxyzine, and methadone. After returning from the
      dentist, the child appeared groggy and was allowed to sleep. A few hours later,
      he was found unresponsive, and following resuscitation attempts at a local
      medical center, he was pronounced dead. Toxicological analyses of femoral blood
      indicated the presence of hydroxyzine at less than 0.54 MUg/mL, trichloroethanol
      (TCE) at 8.3 MUg/mL, and methadone at 0.51 MUg/mL. No meperidine was detected.
      The cause of death was reported to be due to the toxic effects of methadone. The
      toxicological analysis was corroborated by the analysis of the contents of the
      dental cocktail, which revealed the presence of hydroxyzine, chloral hydrate, and
      methadone. Residue from a control sample obtained from the same pharmacy, but
      administered to a different subject, was found to contain hydroxyzine, chloral
      hydrate, and meperidine. This report represents the first known fatality due to
      accidental substitution of methadone in a dental cocktail.

PMID- 21871163
TI  - A fatal case of simultaneous ingestion of mirtazapine, escitalopram, and valproic
      acid.
AB  - Mirtazapine, escitalopram, and valproic acid are newer antidepressant drugs than
      traditional tricyclic antidepressants and are supposed to be less toxic.
      Nevertheless, intoxication cases due to their overdosage have been repeatedly
      reported. In the case presently reported, a 64-year-old woman with a previous
      history of chronic depression was found dead in her apartment. Several packages
      of pharmaceutical drugs were found, including mirtazapine, escitalopram, and
      valproic acid. During the autopsy, no evidence of natural disease or trauma was
      found to account for this death. In order to determine whether massive drug
      assumption might have determined a lethal intoxication, heart blood, urine, and
      gastric content were collected and submitted to toxicological analysis. Specific
      liquid chromatography-tandem mass spectrometry protocols were purposely developed
      and validated. Blood concentrations of mirtazapine, escitalopram, and valproic
      acid were 20.3, 65.5, and 417 mg/L, respectively, whereas urine concentrations
      were 17.0, 94.5, and 423 mg/L, respectively. High concentrations of these drugs
      were also detected in the gastric content, confirming their ingestion shortly
      before death. The agreement between authoptic examination by forensic
      pathologists and toxicological findings are consistent with the suicidal
      hypothesis, where the death arose by drug intoxication due to simultaneous high
      dosage ingestion of mirtazapine, escitalopram, and valproic acid.

PMID- 21871164
TI  - Homicidal methanol poisoning in a child.
AB  - A case of homicidal poisoning of a 21-month-old child using methanol is
      presented. The child was found dead in his crib during a court-ordered visit to
      his father's home. He reportedly was experiencing "flu-like" symptoms the day
      before. Routine toxicology testing of specimens taken at autopsy revealed the
      presence of methanol in a concentration of 0.21%, 0.23%, 0.31%, 0.28%, and 0.26%
      (w/v or w/w) in heart blood, venous blood, urine, vitreous humor, and gastric
      contents, respectively. Formic acid concentrations were 1.0 and 6.4 g/L in heart
      blood and urine. No other drugs or chemicals were detected in comprehensive
      screening. Accidental ingestion of methanol was ruled out; however, the homicide
      investigation was complicated by the fact that up to seven adults at three
      different locations had been involved in the child's care. Minimal information in
      the literature on the time frame for the development of symptoms of methanol
      intoxication in a child of this age made predicting a likely time of ingestion
      difficult. Discussion of the investigation and the timeline for the poisoning
      that was eventually established are included.

PMID- 21871165
TI  - A guide to the Simulium damnosum complex (Diptera: Simuliidae) in Nigeria, with a
      cytotaxonomic key for the identification of the sibling species.
AB  - Although approximately 40% of all the people blinded by Onchocerca volvulus are
      Nigerians, almost nothing was known about the various cytospecies of the blackfly
      vectors present in Nigeria until 1981. The activation of the Nigerian National
      Onchocerciasis Control Programme in 1986 (and that programme's initiation of mass
      distributions of ivermectin in 1991) provided a significant stimulus to
      understand the biology of the Nigerian vectors but the exploration of any
      possible differences between the cytospecies has been hampered by a lack of
      accessible taxonomic information. This review attempts to satisfy that need.
      There are nine different cytoforms reliably recorded from Nigeria (Simulium
      damnosum s.s. Nile form, S. damnosum s.s. Volta form, S. sirbanum Sirba form, S.
      sirbanum Sudanense form, S. soubrense Beffa form, S. squamosum A, S. squamosum B,
      S. squamosum C and S. yahense typical form), and three more are known from
      surrounding countries and might be reasonably expected to occur in Nigeria. All
      of these cytospecies are presumed to be vectors, although there have been almost
      no identifications of the vectors of O. volvulus in Nigeria. The biogeographical
      distribution of the cytoforms is broadly similar to that known in other parts of
      West Africa (although many of the cytoforms remain insufficiently studied). The
      physico-chemical hydrology of the Nigerian breeding sites of the cytospecies does
      not, however, correspond to that seen elsewhere in West Africa, and it is not
      clear whether this might be related to differences in the cytoforms. An
      illustrated cytotaxonomic key is presented to facilitate and encourage future
      studies.

PMID- 21871166
TI  - High prevalences of infection with Giardia intestinalis genotype B among children
      in urban and rural areas of Argentina.
AB  - The protozoan parasite most frequently associated with diarrhoea worldwide is
      Giardia intestinalis. In 2005, a study was initiated to identify the genotypes of
      this parasite infecting children in the Argentinian provinces of Buenos Aires,
      Mendoza and Chaco, and to explore the associations between the genotype detected
      in a child, the characteristics of the child's household and the child's clinical
      presentation. Overall, 998 children (504 boys and 494 girls) aged between 2-14
      years, with or without symptoms, were enrolled. The G. intestinalis in 94 of the
      117 stool samples found positive for the parasite by microscopy were successfully
      genotyped by PCR. Seventy-seven of the children were found to be infected with
      genotype B only and 14 with genotype AII only, three children being found to have
      mixed (AII and B) infections. Only genotype B was detected in children from rural
      areas (P<0.05) and most Giardia detected in children from households with a piped
      water supply were also of this genotype (P<0.05). The other household
      characteristics investigated (quality of building, history of flooding, type of
      sanitation, level of overcrowding, and presence/absence of pet dogs) had no
      significant effect on the genotype distribution. Children infected with genotype
      AII were significantly younger than those infected with genotype B (P<0.05) and
      there was a significant positive association between infection with genotype B
      and abdominal pain (P<0.05). Diarrhoea was not, however, found to be
      significantly associated with genotype-AII or genotype-B infection. This is the
      first published report on the Giardia genotypes circulating in the provinces of
      Mendoza and Chaco. The results indicate the importance of asymptomatic children
      in the transmission of Giardia among the young.

PMID- 21871167
TI  - A dot-ELISA using a partially purified cathepsin-L-like protein fraction from
      Taenia solium cysticerci, for the diagnosis of human neurocysticercosis.
AB  - Human neurocysticercosis (NCC), caused by the cestode Taenia solium, is
      responsible for a significant amount of neurological morbidity and epilepsy in
      developing countries. The disease remains highly endemic in many areas, despite
      several efforts and interventions to control it. A simple, cheap and fast
      diagnostic assay that is suitable for use in field conditions is highly desired.
      In immunodiagnostics based on western immunoblots or standard ELISA, a cathepsin
      L-like protein purified from the cysticercus fluid has previously performed well
      as an antigen. In a recent study in Peru, the same 53/25-kDa antigen was
      therefore used in the development of a dot-ELISA that could be employed for mass
      screenings under field conditions. The assay was standardized and tested not only
      against sera from a large group of NCC cases but also against sera from patients
      with other common parasitic infections, so that sensitivity and specificity could
      be assessed. For NCC, the assay gave better sensitivity in the detection of
      individuals with extraparenchymal cysts (94.4%-100%) or multiple parenchymal
      cysts (74.6%-80.0%) than in the detection of individuals with single parenchymal
      cysts (29.4%-45.1%). The assay also showed a high specificity for NCC (99.0%
      100%), with a very low level of cross-reactivity with other parasitic infections.
      The dot-ELISA developed in this study is a highly specific, simple, cheap and
      rapid test for NCC that could be used under field conditions, even in the low
      resource settings that are common in developing countries.

PMID- 21871168
TI  - The PCR-based detection of Leishmania major in Mus musculus and other rodents
      caught in southern Iran: a guide to sample selection.

PMID- 21871169
TI  - Changes in the distribution of human schistosomiasis in Far North province,
      Cameroon, since 1986.

PMID- 21871170
TI  - Dihydroartemisinin-praziquantel combinations and multiple doses of
      dihydroartemisinin in the treatment of Schistosoma japonicum in experimentally
      infected mice.

PMID- 21871171
TI  - Strongyloidiasis presenting as eosinophilic ascites.

PMID- 21871172
TI  - The role of peroxidases in the pathogenesis of atherosclerosis.
AB  - Reactive oxygen species (ROS), which include superoxide anions and peroxides,
      induce oxidative stress, contributing to the initiation and progression of
      cardiovascular diseases involving atherosclerosis. The endogenous and exogenous
      factors hypercholesterolemia, hyperglycemia, hypertension, and shear stress
      induce various enzyme systems such as nicotinamide adenine dinucleotide
      (phosphate) oxidase, xanthine oxidase, and lipoxygenase in vascular and immune
      cells, which generate ROS. Besides inducing oxidative stress, ROS mediate
      signaling pathways involved in monocyte adhesion and infiltration, platelet
      activation, and smooth muscle cell migration. A number of antioxidant enzymes
      (e.g., superoxide dismutases, catalase, glutathione peroxidases, and
      peroxiredoxins) regulate ROS in vascular and immune cells. Atherosclerosis
      results from a local imbalance between ROS production and these antioxidant
      enzymes. In this review, we will discuss 1) oxidative stress and atherosclerosis,
      2) ROS-dependent atherogenic signaling in endothelial cells, macrophages, and
      vascular smooth muscle cells, 3) roles of peroxidases in atherosclerosis, and 4)
      antioxidant drugs and therapeutic perspectives.

PMID- 21871173
TI  - The functions of mTOR in ischemic diseases.
AB  - Mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase and that forms
      two multiprotein complexes known as the mTOR complex 1 (mTORC1) and mTOR complex
      2 (mTORC2). mTOR regulates cell growth, proliferation and survival. mTORC1 is
      composed of the mTOR catalytic subunit and three associated proteins: raptor,
      mLST8/GbetaL and PRAS40. mTORC2 contains mTOR, rictor, mLST8/GbetaL, mSin1, and
      protor. Here, we discuss mTOR as a promising anti-ischemic agent. It is believed
      that mTORC2 lies down-stream of Akt and acts as a direct activator of Akt. The
      different functions of mTOR can be explained by the existence of two distinct
      mTOR complexes containing unique interacting proteins. The loss of TSC2, which is
      upstream of mTOR, activates S6K1, promotes cell growth and survival, activates
      mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and
      suppresses S6K1 and Akt. Although mTOR signaling pathways are often activated in
      human diseases, such as cancer, mTOR signaling pathways are deactivated in
      ischemic diseases. From Drosophila to humans, mTOR is necessary for Ser473
      phosphorylation of Akt, and the regulation of Akt-mTOR signaling pathways may
      have a potential role in ischemic disease. This review evaluates the potential
      functions of mTOR in ischemic diseases. A novel mTOR-interacting protein
      deregulates over-expression in ischemic disease, representing a new mechanism for
      controlling mTOR signaling pathways and potential therapeutic strategies for
      ischemic diseases.

PMID- 21871174
TI  - Establishment and characterization of an immortalized human dermal papilla cell
      line.
AB  - Establishment of immortalized human dermal papilla cells (DPCs) retaining the
      characteristics of DPCs would be a great help for hair researchers. We recently
      established a simian virus 40T (SV40T)-transformed human DP cell line (SV40TDPC).
      However, the cell line senesced around passage 25 and ceased proliferation. In
      this study, we introduced the human telomerase reverse transcriptase (hTERT) gene
      into SV40T-DPC and established an immortalized human DP cell line. The cell line,
      SV40T-hTERT-DPC, did not induce tumors when inoculated into nude mice. SV40T
      hTERT-DPC maintained morphology of early passage DPCs, expressed markers of DPCs,
      and retained responses to Wnt/beta-catenin and bone morphogenic protein (BMP)
      signaling pathways known to be required for hair-inducing activity of DPCs. The
      data strongly suggest that SV40T-hTERT-DPC retains many characteristics of human
      DPCs in vivo without malignant transformation.

PMID- 21871175
TI  - Niclosamide induces mitochondria fragmentation and promotes both apoptotic and
      autophagic cell death.
AB  - Mitochondrial dynamics not only involves mitochondrial morphology but also
      mitochondrial biogenesis, mitochondrial distribution, and cell death. To identify
      specific regulators to mitochondria dynamics, we screened a chemical library and
      identified niclosamide as a potent inducer of mitochondria fission. Niclosamide
      promoted mitochondrial fragmentation but this was blocked by down-regulation of
      Drp1. Niclosamide treatment resulted in the disruption of mitochondria membrane
      potential and reduction of ATP levels. Moreover, niclosamide led to apoptotic
      cell death by caspase-3 activation. Interestingly, niclosamide also increased
      autophagic activity. Inhibition of autophagy suppressed niclosamide-induced cell
      death. Therefore, our findings suggest that niclosamide induces mitochondria
      fragmentation and may contribute to apoptotic and autophagic cell death.

PMID- 21871176
TI  - Downregulation of ARFGEF1 and CAMK2B by promoter hypermethylation in breast
      cancer cells.
AB  - To identify novel genes that are regulated by promoter methylation, a
      combinational approach involving in silico mining followed by molecular assay was
      performed. From the expression microarray data registered in the European
      bioinformatics institute (EBI), genes showing downregulation in breast cancer
      cells were initially screened and then selected by e-Northern analysis using the
      Unigene database. A series of these in silico methods identified CAMK2B and
      ARFGEF1 as candidates, and the two genes were revealed to be hypermethylated in
      breast cancer cell lines and hypomethylated in normal breast cell lines.
      Additionally, cancer cell lines showed downregulated expression of these genes.
      Furthermore, treatment of the cancer cell lines with a demethylation agent, 5-Aza
      2'-deoxycytidine, recovered expression of CAMK2B and ARFGEF1, implying that
      hypermethyaltion silenced gene activity in cancer cells. Taken together, promoter
      methylations of CAMK2B and ARFGEF1 are novel epigenetic markers identified in
      breast cancer cell lines and can be utilized for the application to clinical
      cancer tissues.

PMID- 21871177
TI  - Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G2/M phase.
AB  - Ribosomal protein S3 (rpS3) is a multifunctional protein involved in translation,
      DNA repair, and apoptosis. The relationship between rpS3 and cyclin-dependent
      kinases (Cdks) involved in cell cycle regulation is not yet known. Here, we show
      that rpS3 is phosphorylated by Cdk1 in G2/M phase. Co-immunoprecipitation and GST
      pull-down assays revealed that Cdk1 interacted with rpS3. An in vitro kinase
      assay showed that Cdk1 phosphorylated rpS3 protein. Phosphorylation of rpS3
      increased in nocodazole-arrested mitotic cells; however, treatment with Cdk1
      inhibitor or Cdk1 siRNA significantly attenuated this phosphorylation event. The
      phosphorylation of a mutant form of rpS3, T221A, was significantly reduced
      compared with wild-type rpS3. Decreased phosphorylation and nuclear accumulation
      of T221A was much more pronounced in G2/M phase. These results suggest that the
      phosphorylation of rpS3 by Cdk1 occurs at Thr221 during G2/M phase and, moreover,
      that this event is important for nuclear accumulation of rpS3.

PMID- 21871178
TI  - Epigenetic characterization of the PBEF and TIMP-2 genes in the developing
      placentae of normal mice.
AB  - Reprogramming errors, which appear frequently in cloned animals, are reflected by
      aberrant gene expression. We previously reported the aberrant expression of TIMP
      2 and PBEF in cloned placenta and differential expression of PBEF genes during
      pregnancy. To examine the epigenetic modifications that regulate dynamic gene
      expression in developing placentae, we herein analyzed the mRNA and protein
      expression levels of PBEF and TIMP-2 in the placentae of normal mice during
      pregnancy and then examined potential correlations with epigenetic modifications.
      DNA methylation pattern analysis revealed no difference, but ChIP assays using
      antibodies against H3-K9/K14 and H4-K5 histone acetylation revealed that the H3
      K9/K14 acetylation levels, but not the H4-K5 acetylation levels, of the TIMP-2
      and PBEF loci were significantly correlated with their gene expression levels
      during placentation in normal mice. These results suggest that epigenetic changes
      may regulate gene expression level in the developing placentae of normal mice and
      that inappropriate epigenetic reprogramming might be one cause of the abnormal
      placentae seen in cloned animals.

PMID- 21871179
TI  - FSCB phosphorylation in mouse spermatozoa capacitation.
AB  - It is generally accepted that spermatozoa capacitation is associated with protein
      kinase A-mediated tyrosine phosphorylation. In our previous study, we identified
      the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA.
      However, the phosphorylation status of FSCB protein during spermatozoa
      capacitation should be further investigated. To this aim, in this study, we found
      that phosphorylation of this 270-kDa protein occurred as early as 1 min after
      mouse spermatozoa capacitation, which increased over time and remained stable
      after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and
      Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The
      extent of phosphorylation and was closely associated with the PKA activity and
      spermatozoa motility characteristics. FSCB phosphorylation could be induced by
      PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB
      contributes to spermatozoa capacitation in a tyrosine-phosphorylated format,
      which may help in further elucidating the molecular mechanism of spermatozoa
      capacitation.

PMID- 21871180
TI  - Suppression of MED19 expression by shRNA induces inhibition of cell proliferation
      and tumorigenesis in human prostate cancer cells.
AB  - MED19 is a member of the Mediator that plays a key role in the activation and
      repression of signal transduction or the regulation of transcription in
      carcinomas. To tested the functional role of MED19 in human prostate cancer, we
      downregulated MED19 expression in prostate cancer cells (PC-3 and DU145) by
      lentivirus-mediated short hairpin (shRNA), and analyzed the effect of inhibition
      of MED19 on prostate cancer cell proliferation and tumorigenesis. The in vitro
      prostate cancer cell proliferation, colony formation, and in vivo tumor growth in
      nude mice xenografts was significantly reduced after the downregulation of MED19.
      Knockdown of MED19 caused S-phase arrest and induced apoptosis via modulation of
      Bid and Caspase 7. It was suggested that MED19 serves as a novel proliferation
      regulator that promotes growth of prostate cancer cells.

PMID- 21871181
TI  - NF-Y binds to both G1- and G2-specific cyclin promoters; a possible role in
      linking CDK2/Cyclin A to CDK1/Cyclin B.
AB  - We previously reported that CDK2/Cyclin A can phosphorylate and activate the
      transcription factor NF-Y. In this study, we investigated a potential regulatory
      role for NF-Y in the transcription of Cyclin A and other cell cycle regulatory
      genes. Gel-shift assays demonstrate that NF-Y binds to CCAAT sequences in the
      Cyclin A promoter, as well as to those in the promoters of cell cycle G2
      regulators such as CDC2, Cyclin B and CDC25C. Furthermore, expression of Cyclin A
      increases NF-Y's affinity for CCAAT sequences in the CDC2 promoter; however,
      Cyclin A's induction of CDC2 transcription is antagonized by p21, an inhibitor of
      CDK2/Cyclin A. These results suggest a model wherein NF-Y binds to and activates
      transcription from the Cyclin A promoter, increasing cellular levels of Cyclin
      A/CDK2 and potentiating NF-Y's capacity for transcriptional transactivation, and
      imply a positive feedback loop between NF-Y and Cyclin A/CDK2. Our findings are
      additionally indicative of a role for Cyclin A in activating Cyclin B/CDK1
      through promoting NF-Y dependent transcription of Cyclin B and CDC2; NF-Y
      mediated crosstalk may therefore help to orchestrate cell-cycle progression.

PMID- 21871182
TI  - Comparing the coding of complications in Queensland and Victorian admitted
      patient data.
AB  - OBJECTIVE: To examine differences between Queensland and Victorian coding of
      hospital-acquired conditions and suggest ways to improve the usefulness of these
      data in the monitoring of patient safety events. DESIGN: Secondary analysis of
      admitted patient episode data collected in Queensland and Victoria. METHODS:
      Comparison of depth of coding, and patterns in the coding of ten commonly coded
      complications of five elective procedures. RESULTS: Comparison of the mean
      complication codes assigned per episode revealed Victoria assigns more valid
      codes than Queensland for all procedures, with the difference between the states
      being significantly different in all cases. The proportion of the codes flagged
      as complications was consistently lower for Queensland when comparing 10 common
      complications for each of the five selected elective procedures. The estimated
      complication rates for the five procedures showed Victoria to have an apparently
      higher complication rate than Queensland for 35 of the 50 complications examined.
      CONCLUSION: Our findings demonstrate that the coding of complications is more
      comprehensive in Victoria than in Queensland. It is known that inconsistencies
      exist between states in routine hospital data quality. Comparative use of patient
      safety indicators should be viewed with caution until standards are improved
      across Australia. More exploration of data quality issues is needed to identify
      areas for improvement.

PMID- 21871183
TI  - Prevalence and prevention of workplace aggression in Australian clinical medical
      practice.
AB  - OBJECTIVE: To determine the extent of aggression directed towards Australian
      doctors and the implementation of aggression prevention and minimisation
      strategies in medical workplaces. METHODS: Data were obtained from the pilot
      phase (n=321) of the Medicine in Australia: Balancing Employment and Life survey
      of the clinical medical workforce in 2010. Descriptive statistics were generated
      in relation to doctors' experiences of aggression at work in the previous 12
      months, and the implementation of workplace aggression prevention and
      minimisation strategies. Distributions of the outcome variables were evaluated by
      doctor type and sex. RESULTS: More than 70% of doctors experienced verbal or
      written aggression and almost a third experienced physical aggression. Higher
      proportions of hospital non-specialists and specialists-in-training experienced
      aggression from patients, patient relatives or carers and co-workers. Higher
      proportions of female doctors experienced verbal or written aggression from
      patient relatives or carers and co-workers. Overall, the more basic aggression
      prevention and minimisation strategies had been implemented in approximately two
      thirds of clinical settings, with lower rates for more extended strategies.
      CONCLUSIONS: Many Australian doctors experience workplace aggression. The more
      widespread adoption of measures that support the prevention and minimisation of
      aggression in medical practice settings appears necessary.

PMID- 21871184
TI  - Role of Australian primary healthcare organisations (PHCOs) in primary healthcare
      (PHC) workforce planning: lessons from abroad.
AB  - OBJECTIVE: To review international experience in order to inform Australian PHC
      workforce policy on the role of primary healthcare organisations (PHCOs/Medicare
      Locals) in PHC workforce planning. METHOD: A NZ and UK study tour was conducted
      by the lead author, involving 29 key informant interviews with regard to PHCOs
      roles and the effect on PHC workforce planning. Interviews were audio-taped with
      consent, transcribed and analysed thematically. RESULTS: Emerging themes
      included: workforce planning is a complex, dynamic, iterative process and key
      criteria exist for doing workforce planning well; PHCOs lacked a PHC workforce
      policy framework to do workforce planning; PHCOs lacked authority, power and
      appropriate funding to do workforce planning; there is a need to align workforce
      planning with service planning; and a PHC Workforce Planning and Development
      Benchmarking Database is essential for local planning and evaluating workforce
      reforms. CONCLUSION: With the Australian government promoting the role of PHCOs
      in health system reform, reflections from abroad highlight the key action within
      PHC and PHCOs required to optimise PHC workforce planning.

PMID- 21871185
TI  - Paying the right price for pharmaceuticals: a case study of why the comparator
      matters.
AB  - This article considers the pricing policy for pharmaceuticals in Australia, which
      is widely seen as having achieved low drug prices. However, compared to New
      Zealand, the evidence implies that Australia might have improved its performance
      significantly if it had proactively sought market best pricing. The Australian
      record suggests that the information sought by authorities may not be sufficient
      for optimal pricing and that the economic evaluation of pharmaceuticals may be
      neither necessary nor sufficient for achieving this goal.

PMID- 21871186
TI  - Financial incentives and the health workforce.
AB  - Changes to the remuneration of medical practitioners are currently being
      considered in Australia. In this paper, we provide a discussion of financial
      incentives in healthcare markets and their effects on health professionals'
      behaviour. After defining incentives, the paper focuses on the design of
      incentive schemes for the health workforce. It discusses several issues that
      should be considered when designing incentives, illustrated with some Australian
      examples. What are the objectives of the incentive scheme? What types of
      incentives can be used and under what circumstances? What is the empirical
      evidence around the effects of incentive schemes? What unintended consequences
      might exist? The paper concludes with a set of principles around which incentives
      can be designed. These principles might be used to inform the current debate
      about revisions to the incentives that are faced by medical practitioners in
      Australia.

PMID- 21871187
TI  - Resource allocation and economic evaluation in Australia's healthcare system.
AB  - OBJECTIVE: To explore dimensions and varieties of economic evaluations that
      healthcare decision-makers do or do not use. DESIGN: Web-based survey. SETTING
      AND PARTICIPANTS: A purposive sample of Australian healthcare decision-makers was
      recruited by direct invitation through email. All were invited to complete an
      online questionnaire derived from the EUROMET 2004 survey. RESULTS: A total of 91
      questionnaires were analysed. Almost all participants were involved in financial
      resource allocations. Most commonly, participants based their decisions on
      patient needs, effectiveness of interventions, cost of interventions or overall
      budgetary effect, and policy directives. Evidence from cost-effectiveness
      analysis was used by half of the participants. Timing, ethical issues and lack of
      knowledge about economic evaluation were the most significant barriers to the use
      of economic evaluations in resource allocation decisions. Most participants
      reported being moderately to very familiar with the cost-effectiveness analysis.
      There was a general impression that evidence from economic evaluations should
      play a larger role in the future. CONCLUSIONS: Evidence from health economic
      evaluations may provide valuable information in some decisions; however, at
      present, it is not central to many decisions. The study suggests that, for
      economic evaluation to be helpful in real-life policy decisions, it has to be
      placed into context - a context which is complex, political and often resistant
      to voluntary change.

PMID- 21871188
TI  - What is a health emergency? The difference in definition and understanding
      between patients and health professionals.
AB  - BACKGROUND: Investigations into 'inappropriate' use of emergency health services
      are limited by the lack of definition of what constitutes a health emergency.
      Position papers from Australian and international sources emphasise the patient's
      right to access emergency healthcare, and the responsibility of emergency health
      care workers to provide treatment to all patients. However, discordance between
      the two perspectives remain, with literature labelling patient use of emergency
      health services as 'inappropriate'. OBJECTIVE: To define a 'health emergency' and
      compare patient and health professionals perspectives. METHOD: A sample of 600
      emergency department (ED) patients were surveyed about a recent health experience
      and asked to rate their perceived urgency. This rating was compared to their
      triage score allocated at the hospital ED. RESULTS: No significant relationship
      was found between the two ratings of urgency (P=0.51). CONCLUSIONS; Differing
      definitions of a 'health emergency' may explain patient help-seeking behaviour
      when accessing emergency health resources including hospital ED and ambulance
      services. A new definition of health emergency that encapsulates the health
      professional and patient perspectives is proposed. An agreed definition of when
      emergency health resources should be used has the potential to improve emergency
      health services demand and patient flow issues, and optimise emergency health
      resource allocation.

PMID- 21871189
TI  - Shared services arrangement in a decentralising healthcare environment - will it
      work?

PMID- 21871190
TI  - A tale of two cities: responses to the Eyjafjallajokull eruption and lessons for
      health disaster management.

PMID- 21871191
TI  - Closing the (service) gap: exploring partnerships between Aboriginal and
      mainstream health services.
AB  - BACKGROUND: Although effective partnerships between Aboriginal and mainstream
      health services are critical to improve Aboriginal health outcomes, many factors
      can cause these partnerships to be tenuous and unproductive. Understanding the
      elements of best practice for successful partnerships is essential. METHODS: A
      literature review was conducted in 2009 using keyword searches of electronic
      databases. Sourced literature was assessed for relevance regarding the benefits,
      challenges, lessons learnt and factors contributing to successful Aboriginal and
      mainstream partnerships. Key themes were collated. RESULTS: Although there is
      much literature regarding general partnerships generally, few specifically
      examine Aboriginal and mainstream health service partnerships. Twenty-four
      sources were reviewed in detail. Benefits include broadening service capacity and
      improving the cultural security of healthcare. Challenges include the legacy of
      Australia's colonial history, different approaches to servicing clients and
      resource limitations. Recommendations for success include workshopping tensions
      early, building trust and leadership. CONCLUSION: Although successful
      partnerships are crucial to optimise Aboriginal health outcomes, failed
      collaborations risk inflaming sensitive Aboriginal-non-Aboriginal relationships.
      Factors supporting successful partnerships remind us to develop genuine, trusting
      relationships that are tangibly linked to the Aboriginal community. Failure to
      invest in this relational process and push forward with 'business as usual' can
      ultimately have negative ramifications on client outcomes.

PMID- 21871192
TI  - Indigenous participation in an informal national indigenous health policy
      network.
AB  - OBJECTIVE; To determine and describe the features of Indigenous participation in
      an informal national Indigenous health policy network. DESIGN: A questionnaire
      was administered during 2003-04. Through a snowball nomination process a total of
      227 influential persons were identified. Of these, 173 received surveys of which
      44 were returned, a return rate of 25%. OUTCOME MEASURES: These data were
      analysed to detect the existence of network groups; measure the degree of group
      interconnectivity; and measure the characteristics of bonds between influential
      persons. Demographic information was used to characterise the network and its
      groups. RESULTS: Indigenous people were integral to the network due to their high
      representation, their distribution throughout the 16 groups, and the
      interconnections between the groups. The network was demographically diverse and
      multiple relational variables were needed to characterise it. Indigenous and non
      Indigenous people had strong ties in this network. CONCLUSION: Social network
      methods made visible an informal network where Indigenous and non-Indigenous
      people relate in a complex socio-political environment to influence national
      Indigenous health policy. What is known about the topic? The participation of
      Indigenous people is acknowledged as important in health, but there is criticism
      of the lack of real opportunities for Indigenous people to participate in
      national Indigenous health policy processes.

PMID- 21871193
TI  - Appropriate seating for medical patients: an audit.
AB  - OBJECTIVE: To determine the number and types of chairs available for patient use;
      to establish minimum criteria of appropriate chairs; and to assess the
      suitability of available chairs to seat patients admitted to medical wards.
      METHODS: Audit of chairs available in medical wards in a tertiary referral public
      hospital was conducted. All chairs relevant to patient use were photographed and
      counted. An expert panel determined minimum criteria of appropriate seating for
      older patients from functional, occupational health and safety, ergonomic,
      infection control and usability viewpoints. The number of chairs meeting the
      minimum criteria level was recorded and was expressed as a percentage of the
      number of required chairs (hospitalised patients able to be sat out of bed).
      RESULTS: A total of 270 chairs of 36 different types were identified. The
      majority of chairs, 231 (85%), did not meet the minimum criteria. Thirty-nine
      chairs met the minimum criteria for patients to sit in with 113 (66%) patients
      unable to sit out of bed. CONCLUSION: This study identified that there were
      insufficient appropriate chairs available for patients to sit out of bed in this
      facility. This has potential implications for functional ability of the patients,
      particularly for the older person.

PMID- 21871194
TI  - Young people in aged care: progress of the current national program.
AB  - OBJECTIVE: The aim of this paper is to examine the progress and effect of the
      current 5-year $244 million National Young People in Residential Aged Care
      program on the reduction of young people in aged care. METHOD: Semi-structured
      telephone interviews with 20 service providers, 10 advocacy organisations and 6
      public servants across Australia actively involved in the implementation of the
      program. RESULTS: The development of new accommodation options has been slow. The
      5-year program aims to move 689 young people out of nursing homes; in the first 4
      years of the initiative only 139 people had moved out. The lives of those who
      have been helped by the program have been enormously improved. CONCLUSIONS: This
      study highlights the challenges of achieving a long-term reduction in the number
      of young people in residential aged care, including the challenge of achieving
      systemic change to prevent new admissions. Implications. The accommodation
      options currently being developed for this target group will soon be at capacity.
      Without sustained investment in developing alternative accommodation options and
      resources to implement systemic change ~250 people under 50 are likely to
      continue to be admitted to aged care each year in Australia.

PMID- 21871195
TI  - Red alert - a new perspective on patterns of blood use in the South Australian
      public sector.
AB  - OBJECTIVES: In 2006 South Australia had a red cell issue rate, measured as
      product issues per 1000 population, 22.4% higher than the national average. A
      pilot study was undertaken to investigate the disparity in issue rates between SA
      and the national average with a secondary aim of establishing information on SA
      red cell use. METHODS: A linked electronic database was developed using clinical,
      epidemiological and red cell transfusion data within hospitals in the SA public
      sector. Aggregated red cell use across the SA public health sector was analysed
      by clinical variables such as Diagnosis Related Group (DRG), including specialty
      related groups (SRGs) and major diagnostic categories (MDCs). The DRGs that were
      associated with blood use were identified and applied to national hospital
      separations data in order to derive comparative blood utilisation rates for SA
      and Australia. RESULTS: Although blood issue and usage by population measure
      showed a significant difference of 22.4 and 22.0% respectively between SA and
      Australia, when measured against weighted separations the differences reduced to
      7.4 and 7.1% respectively. CONCLUSION: This study showed the importance of
      analysing blood issues and utilisation on an activity adjusted basis rather than
      a raw per capita basis.

PMID- 21871196
TI  - Effects of the Medicare enhanced primary care program on primary care physician
      contact in the population of older Western Australians with chronic diseases.
AB  - OBJECTIVE: Assess uptake of Medicare's enhanced primary care (EPC) services in
      Western Australia (WA) in 2001 to 2006, evaluating effect of EPC services on the
      regularity of contact with general practitioners (GPs) in patients aged 65+
      years. METHOD: Whole-population cohort study using linked routinely collected
      health service data from State and Federal health databases. Analyses include age
      standardised rate of EPC services, odds of EPC utilisation relative to other GP
      services using logistic regression, and total GP service regularity pre- and post
      implementation of the EPC program. RESULTS: EPC services provided to WA seniors
      increased 345% 2001 to 2006, comprising an increasing proportion of the total GP
      services (1.1 to 3.6%). Uptake of EPC services accelerated abruptly after 2004
      due to greater use of 'care plans'. EPC services were associated with a history
      of chronic disease, especially type 2 diabetes (OR=1.74, 95% CI 1.66-1.82).
      Regularity of total GP services was improved with any EPC service exposure, with
      greater improvement occurring in the presence of annual EPC service exposure.
      CONCLUSIONS: EPC item uptake responded favourably to item changes from Medicare
      Australia. Prior exposure to EPC items increased the regularity of GP services,
      an outcome inversely associated with chronic disease progression.

PMID- 21871197
TI  - How much do we spend on prescription medicines? Out-of-pocket costs for patients
      in Australia and other OECD countries.
AB  - OBJECTIVES: To determine changes in out-of-pocket expenditure on prescription
      medicines for Australian patients, and how patient expenditure compares with
      other Organisation for Economic Co-operation and Development (OECD) countries.
      METHODS: We examined out-of-pocket expenditure on prescription medicines by
      patients in Australia between 1970 and 2007, and between Australia and 15 other
      OECD countries (Canada, Czech Republic, Denmark, Finland, France, Germany, Japan,
      Republic of Korea (South Korea), Luxembourg, Poland, Slovak Republic, Spain,
      Sweden, Switzerland and the United States) in 2005. FINDINGS: Spending on
      publicly subsidised medicines by Australian patients increased from $16 per
      person in 1971 to $62 in 2007. Patient expenditure on all prescription medicines
      had risen to $134 per person in 2007. Out-of-pocket expenditure for Australian
      patients ranked 4th of 14 OCED countries with universal pharmaceutical subsidies.
      Australian patients pay 28% of national pharmaceutical expenditure; more than
      patients in South Korea (27%), Slovak Republic (26%), Sweden (22%), France,
      Luxembourg, Japan and Switzerland (17%), Germany (15%), Czech Republic (11%) and
      Spain (6%), but less than patients in Finland (36%), Denmark (33%) and Poland
      (34%). CONCLUSIONS: Compared to other OECD countries, Australian out-of-pocket
      costs are now in the mid to upper range. Further increases have the potential to
      significantly affect access to care.

PMID- 21871198
TI  - A residential aged care end-of-life care pathway (RAC EoLCP) for Australian aged
      care facilities.
AB  - The objective of this study was to develop, implement and evaluate an end-of-life
      (terminal) care pathway and associated infrastructure suitable for Australian
      residential aged care facilities that improves resident and health system
      outcomes. The residential aged care end-of-life care pathway was developed by a
      multidisciplinary collaboration of government and non-government professionals
      and incorporated best clinical management for dying residents to guide care and
      increase palliative care capacity of generalist staff. Implementation included
      identifying and up-skilling Link Nurses to champion the pathway, networking
      facilities with specialist palliative care services, delivering education to
      generalists and commencing a Palliative Care Medication Imprest System in each
      facility. The primary outcome measure for evaluation was transfer to hospital;
      secondary measures included staff perceived changes in quality of palliative care
      provided and family satisfaction with care. Results indicated that the pathway,
      delivered within a care framework that guides provision of palliative care,
      resulted in improved resident outcomes and decreased inappropriate transfers to
      acute care settings.

PMID- 21871199
TI  - Effective discharge planning - timely assignment of an estimated date of
      discharge.
AB  - OBJECTIVE: To examine the implementation of estimated date of discharge (EDD) for
      planned admissions and admissions via the emergency department, to assess the
      variance between EDD and the actual date of discharge (ADD), and to explore the
      determinants of delayed discharge in a tertiary referral centre, Sydney,
      Australia. METHODS: Primary data from a convenience sample of 1958 admissions for
      allocation of EDDs were linked with administrative data. The window for assigning
      EDDs for planned admissions was 24h, for admissions via the emergency department
      it was 48h. Logistic regression models were used to examine the key factors
      associated with an EDD being assigned within 24h or 48h of an admission. An
      ordinal logistic regression model was used to explore the determinants of delayed
      discharge. RESULTS: Only 13.4% of planned admissions and 27.5% of admissions via
      the emergency department were allocated a timely EDD. Older patients, patients
      with significant burdens of chronic morbidity (OR=0.903; P=0.011); and patients
      from a non-English-speaking background (OR=0.711; P=0.059) were less likely to be
      assigned a timely EDD. The current Charlson Index score was a significant
      predictor of a positive variance between EDD and ADD. CONCLUSIONS: The prevalence
      of the timely assignment of an EDD was low and was lowest for planned admissions.
      The current Charlson Index score is an effective tool for identifying patients
      who are more likely to experience delayed discharge.

PMID- 21871200
TI  - Hospital discharge: recommendations for performance improvement for family carers
      of people with dementia.
AB  - BACKGROUND; It is acknowledge that discharge planning benefits both consumers and
      hospitals. What is not widely understood is the experience that the family carer
      of a person with a dementia has and whether the hospitals meet their in-hospital
      and post-hospital needs. OBJECTIVE: To explore whether metropolitan and rural
      hospital discharge practices meet the needs of the family carer of a person with
      dementia. RESULTS: Although this and other research indicates that a continuum of
      care model is beneficial to family caregivers, no evidence has been identified
      that family carers currently experience this type of quality planning. Family
      carers were often unaware of the existence of a hospital discharge plan and were
      rarely engaged in communication about the care of their family member with a
      dementia or prepared for discharge. CONCLUSION AND RECOMMENDATIONS; Discharge
      planning processes for family carers of people with dementia could be
      substantially improved. It is recommended that hospitals develop policy, process
      and procedures that take into account the family carer's needs, develop key
      performance indicators and adopt best practice standards that direct discharge
      planning activities and early engagement of the family carer in healthcare
      decisions. It is recommended that health professionals be educated on
      communication, consultation and needs of family carers.

PMID- 21871201
TI  - Do triage systems in healthcare improve patient flow? A systematic review of the
      literature.
AB  - OBJECTIVES: Triage processes are often used by Emergency Departments to sort
      patients according to urgency or type of service required. Triage may also be
      used in a broad spectrum of other health services and not just emergency
      departments. Triage systems may be used to ensure the most urgent patients get
      timely service, but do they have an effect on patient flow? METHODS: We conducted
      a systematic review by searching five electronic databases (until August 2009)
      combining the elements 'triage' and 'patient flow', complemented by hand
      searching reference lists and citation tracking. We identified and assessed the
      quality of 25 articles that met inclusion criteria. Population, setting, design
      and results were extracted and a process of descriptive synthesis applied. Effect
      sizes for waiting time were compared for seven studies in which sufficient data
      could be extracted. RESULTS AND CONCLUSION: Moderate evidence exists from a range
      of health services that the ability to combine triage and initial treatment in
      less resource intensive cases can have a positive effect on patient flow. There
      is conflicting evidence that triage systems that only prioritize patients,
      without providing any treatment, improve overall patient flow, although tailoring
      triage criteria more specifically to the patient population or using triage to
      prioritize treatable cases may be of benefit.

PMID- 21871202
TI  - From theory to practice of electronic handover.
AB  - Clinical handover is an essential process occurring at many levels of inpatient
      care. Multiple studies within a hospital setting have identified that a breakdown
      in the handover process can lead to poor patient outcomes and serious adverse
      events. The use of electronic handover tools is an intervention identified to
      decrease errors in clinical care arising from poor handover practice. An
      electronic handover tool was implemented in a general medical unit in a
      metropolitan tertiary hospital setting. The program was written by a Medical
      Professional who also used the tool. The program was evaluated with a pre- and
      post-intervention survey within the medical, allied health and nursing staff
      members of the multidisciplinary teams. The use of the Electronic Handover
      program resulted in improved satisfaction of the handover process within the
      medical, nursing and allied health professions. This trial demonstrates that an
      electronic handover program can be successfully integrated into normal medical
      work practice, resulting in positive outcomes for a multidisciplinary staff team.
      Further work is required to determine whether patient outcomes are improved as a
      result.

PMID- 21871203
TI  - Study of the proacrosin-acrosin system in epididymal, ejaculated and in vitro
      capacitated boar spermatozoa.
AB  - The present study aimed to develop a set of sensitive assays to evaluate the
      presence of different isoforms, the activity degree, and the immunolocalisation
      of proacrosin-acrosin in sexually mature boars. The goal was to determine the
      proacrosin-acrosin status of boar spermatozoa throughout epididymal maturation,
      during ejaculation and after in vitro capacitation. In epididymal samples,
      proacrosin expression was high in all regions studied. In contrast, alpha- and
      beta-acrosin expression was low in the caput region, and increased progressively
      during maturation and in vitro capacitation. In in vitro capacitated samples, the
      acrosin activity was 2.25 times higher than in the ejaculated samples and
      immunolocalisation analyses showed redistribution of proacrosin-acrosin at the
      apical ridge of the head. This study provides relevant data about the expression,
      localisation and activity of the proacrosin-acrosin system in healthy adult boars
      that can be used as a base to analyse changes in the proacrosin-acrosin system
      under pathological conditions.

PMID- 21871204
TI  - The conformation and activation of Fyn kinase in the oocyte determine its
      localisation to the spindle poles and cleavage furrow.
AB  - Several lines of evidence imply the involvement of Fyn, a Src family kinase, in
      cell-cycle control and cytoskeleton organisation in somatic cells. By live cell
      confocal imaging of immunostained or cRNA-microinjected mouse oocytes at
      metaphase of the second meiotic division, membrane localisation of active and non
      active Fyn was demonstrated. However, Fyn with a disrupted membrane-binding
      domain at its N-terminus was targeted to the cytoplasm and spindle in its non
      active form and concentrated at the spindle poles when active. During metaphase
      exit, the amount of phosphorylated Fyn and of spindle-poles Fyn decreased and it
      started appearing at the membrane area of the cleavage furrow surrounding the
      spindle midzone, either asymmetrically during polar body II extrusion or
      symmetrically during mitosis. These results demonstrate that post-translational
      modifications of Fyn, probably palmitoylation, determine its localisation and
      function; localisation of de-palmitoylated active Fyn to the spindle poles is
      involved in spindle pole integrity during metaphase, whereas the localisation of
      N-terminus palmitoylated Fyn at the membrane near the cleavage furrow indicates
      its participation in furrow ingression during cytokinesis.

PMID- 21871205
TI  - Colloid centrifugation removes seminal plasma and cholesterol from boar
      spermatozoa.
AB  - The objective of the present study was to investigate the effect of Single-Layer
      Centrifugation (SLC) on boar spermatozoa, namely the effect of removal of seminal
      plasma proteins and cholesterol from the surface of spermatozoa. The presence of
      porcine seminal plasma proteins I and II (PSP-I/PSP-II) before and after SLC was
      studied using immunofluorescence, whereas the removal of cholesterol was shown
      qualitatively by thin-layer chromatography (TLC). Finally, the integrity of the
      sperm plasma membrane was observed by electron microscopy. It was shown that the
      seminal plasma proteins PSP-I and -II were removed from spermatozoa during SLC
      but could be restored by adding seminal plasma to the SLC-selected sperm samples.
      Some cholesterol was also lost from the spermatozoa during SLC but the plasma
      membrane itself appeared to be morphologically intact. Further studies are
      underway to examine the relevance of these findings to boar sperm
      cryopreservation and sperm fertility.

PMID- 21871206
TI  - Heterozygous Inverdale ewes show increased ovulation rate sensitivity to pre
      mating nutrition.
AB  - This study aimed to determine whether ewes heterozygous (I+) for the Inverdale
      mutation of the bone morphogenetic protein-15 (BMP15) gene with high natural
      ovulation rate (OR) show similar sensitivity to nutritional manipulation as non
      carriers (++). Increasing pre-mating nutrition results in OR increases in sheep,
      but whether this effect occurs in ewes with naturally high OR is unknown. Over 2
      years, I+ or ++ ewes were given high (ad libitum) or control (maintenance)
      pasture allowances for 6 weeks prior to mating at a synchronised oestrus, with OR
      measured 8 days later. The high group increased in weight compared with controls
      (+5.84kg; P<0.01), accompanied by increased OR (+19%; P<0.01). As well as having
      higher OR (+45%; P<0.01), I+ ewes responded to increased feed with a larger
      proportional increase in OR (+27%; P<0.01) compared with the response in ++ ewes
      (+11%; P<0.05), suggesting an interaction between BMP15 levels and nutritional
      signals in the follicle to control OR. Although litter size increases only tended
      to significance (+12%; P=0.06), extra feed resulted in over 50% of I+ ewes giving
      birth to more than three lambs, compared with 20-31% of I+ ewes on maintenance
      rations. This information can guide feed management of prolific Inverdale ewes
      prior to breeding.

PMID- 21871207
TI  - Involvement of the sphingolipid ceramide in heat-shock-induced apoptosis of
      bovine oocytes.
AB  - Programmed cell death via the sphingomyelin pathway has been suggested to
      underlie heat-shock disturbance of oocyte developmental competence. A series of
      experiments were performed to characterise the role of the sphingolipid ceramide
      in heat-shock-induced apoptosis, and to determine whether ceramide formation can
      be regulated. Bovine cumulus-oocyte complexes (COCs) were aspirated from ovaries
      collected in the cold season (November-April), in vitro-matured, fertilised and
      cultured for 8 days. Exposure of COCs to heat shock (41 degrees C) during
      maturation reduced cleavage rate and blastocyst formation relative to the control
      group (38.5 degrees C). Annexin-V binding (V-FITC assay), which is associated
      with the early apoptotic event of membrane phosphatidylserine turnover, was
      higher in oocytes exposed to short-term versus long-term heat shock, suggesting
      that heat-shock-induced apoptosis involves membrane alterations. Similar to heat
      exposure, oocyte maturation with C(2)-ceramide had a dose-dependent deleterious
      effect on the first cleavages and subsequent embryonic development in association
      with increased annexin-V binding. Blocking endogenous ceramide generation with
      fumonisin B1, a specific inhibitor of dihydroceramide synthase (i.e. de novo
      formation), moderated, to some extent, the effects of heat shock on oocyte
      developmental competence, suggesting that ceramide plays an important role in
      heat-shock-induced apoptosis.

PMID- 21871208
TI  - Restricted feed intake in lactating primiparous sows. I. Effects on sow metabolic
      state and subsequent reproductive performance.
AB  - The effects of feed restriction (60% of anticipated feed intake; Restrict; n=60)
      during the last week of a 21-day lactation in primiparous sows compared with
      feeding at 90% of anticipated feed intake (Control; n=60) on sow metabolic state,
      litter growth and sow reproductive performance after weaning were compared.
      Metabolisable energy (ME) derived from feed was lower, ME derived from body
      tissues was higher and litter growth rate was reduced (all P<0.05) in Restrict
      sows during the last week of lactation. Treatment did not affect weaning-to
      oestrus interval, pregnancy rate, ovulation rate, embryonic survival or the
      number of live embryos (P>0.05) at Day 30 of gestation: However, embryo weight
      was greater (P<0.05) in Control than in Restrict sows (1.55+/-0.04vs 1.44+/
      0.04g, respectively). These data suggest the biology of the commercial sow has
      changed and reproductive performance of contemporary primiparous sows is
      increasingly resistant to the negative effects of lactational catabolism.
      Overall, catabolism negatively affected litter weaning weight and embryonic
      development of the next litter, but the extent to which individual sows used
      tissue mobilisation to support these litter outcomes was highly variable.

PMID- 21871209
TI  - Restricted feed intake in lactating primiparous sows. II. Effects on subsequent
      litter sex ratio and embryonic gene expression.
AB  - Expression of panels of candidate genes controlling myogenesis, angiogenesis and
      gender-specific imprinting of development were analysed in embryonic, placental
      and endometrial tissues recovered at Day 30 of gestation from a subset of
      primiparous sows that were either feed restricted (Restrict; n=17) or fed to
      appetite (Control; n=15) during the last week of the previous lactation. Embryos
      were also sex typed to investigate gender bias in response to treatments. Average
      embryonic weight was lower in the subset of Restrict compared with Control
      litters (1.38+/-0.07vs 1.59+/-0.08g, respectively) and the male:female sex ratio
      was higher (P<0.05) in embryos (litters) recovered from Restrict sows. Treatment
      affected (P<=0.05) the expression of embryonic and placental genes involved in
      insulin-like growth factor (IGF) 2 signalling, including IGF2, INSR and IGF2R.
      Embryonic expression of ESR1 was also affected by treatment (P<0.03) and
      sex*treatment interactions were observed for the expression of embryonic ESR1
      (P<0.05) and placental ANGPT2 (P<0.03). At the molecular level, these results
      support the suggestion that changes in placental function are not the primary
      mechanism mediating detrimental effects of previous sow catabolism on early
      embryonic development in the feed-restricted lactational sow model. However,
      perturbations in the IGF2 system are implicated as mediators of these effects.

PMID- 21871210
TI  - Enhancement of lipid metabolism with L-carnitine during in vitro maturation
      improves nuclear maturation and cleavage ability of follicular porcine oocytes.
AB  - The aim of the present study was to assess the effects of L-carnitine, an
      enhancer of lipid metabolism and mitochondrial activity, during in vitro
      maturation (IVM) on nuclear maturation and in vitro fertilisation of porcine
      follicular oocytes and subsequent embryo development. Mitochondrial functions,
      intracellular lipid content and reactive oxygen species (ROS) levels in oocytes
      were also investigated. L-carnitine supplementation in 0.6-5mgmL(-1)
      concentration during IVM significantly improved (P<0.05) the rates of metaphase
      II (MII) stage oocytes compared with the control; however, fertilisation rates
      and monospermy were not improved. Although supplementation of IVM medium with L
      carnitine significantly increased oocyte cleavage (P<0.05), further development
      to the blastocyst stage was not improved. The density of active mitochondria was
      significantly higher and the density of lipid droplets was significantly lower
      (P<0.05) in L-carnitine-treated oocytes compared with the control. Furthermore,
      the ROS levels in L-carnitine-treated oocytes were significantly lower than those
      in the control. In conclusion, enhancing mitochondrial functions by L-carnitine
      improved oocyte maturation and cleavage underlining the importance of lipid
      metabolism for nuclear and cytoplasmic maturation of porcine oocytes.

PMID- 21871211
TI  - Direct ovarian-uterine transfer of progesterone increases embryo survival in
      gilts.
AB  - This study employed a unilateral ovariectomy model to investigate the relevance
      of the local supply of progesterone (ovary) compared with the systemic supply of
      progesterone, in terms of embryo survival in the ipsilateral uterine horn as
      opposed to the contralateral uterine horn. Thirty gilts were unilaterally
      ovariectomised (ULO) during the luteal stage of their first oestrous cycle. Half
      of the ULO gilts were fed at 1.2 maintenance requirement (M), while the other
      half were fed at 2.4M. Across ULO gilts 0.8 more embryos survived in the
      ipsilateral horn compared with the contralateral horn at Day 35 of gestation
      (P<0.05). In ULO gilts on the 2.4M feed level the difference (+1.3; P<0.05)
      between the ipsi- and contralateral horn was more pronounced than on the 1.2M
      feed level (+0.4; NS). The higher feed level reduced circulating levels of
      systemic progesterone on Day 5 of pregnancy but not embryo survival at Day 35.
      However, post-implantation embryo survival was lower on the low feed level. In
      conclusion, these data indicate that local progesterone supply from the ovaries
      to the uterus contributes to the probability of embryo survival.

PMID- 21871212
TI  - SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity.
AB  - Male obesity is associated with reduced sperm function and increased incidence of
      sperm DNA damage; however, the underlying molecular mechanisms have not yet been
      identified. Mammalian SIRT6 protein is involved in caloric-dependant DNA damage
      repair in other tissue types, yet a possible role for SIRT6 in male obesity and
      subfertility has not been investigated previously. To assess SIRT6 levels and
      activity in the testes, male mice (n=12 per diet) were fed either a control diet
      (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 16 weeks before the collection
      of testes and spermatozoa. SIRT6 protein was localised to the nucleus of
      transitional spermatids and the acrosome of mature spermatozoa, with levels
      significantly decreased in HFD-fed male mice (P<0.05). This decrease in SIRT6
      protein was associated with transitional spermatids having increased levels of
      acetylated H3K9 in the nucleus (P<0.01) and increased DNA damage (P<0.001). We
      propose a role for SIRT6 in spermiogenesis and potentially protamination
      processes, which are known to be compromised by male obesity.

PMID- 21871214
TI  - Usutu virus: potential risk of human disease in Europe.
AB  - Usutu virus (USUV) is an African mosquito-borne flavivirus, member of the
      Japanese encephalitis antigenic group. This avian virus is transmitted by
      arthropod vectors (mainly mosquitoes of the Culex pipiens complex). It is well
      known that free-living birds, including migratory species, have the potential to
      disperse certain pathogenic microorganisms. Usutu virus has recently been
      introduced to Europe and is spreading through Austria, Hungary, Italy, Spain and
      Switzerland, causing disease in birds and humans. Like West Nile virus, USUV may
      become a resident pathogen in Europe and the consequences for public health
      should be considered. Many different biotic and abiotic factors affect the
      survival of the virus in a new environment and influence the efficiency of its
      geographical dispersal. In this article, we consider the possibility of including
      USUV infections among the vector-borne diseases to be monitored in Europe.

PMID- 21871215
TI  - Secondary transmissions during the outbreak of Shiga toxin-producing Escherichia
      coli O104 in Hesse, Germany, 2011.
AB  - During the recent outbreak of Shiga toxin-producing Escherichia coli (STEC)
      O104:H4 in Germany most cases notified in the State of Hesse (6 million
      inhabitants) were linked to satellite clusters or had travelled to the outbreak
      area in northern Germany. Intensified surveillance was introduced to rapidly
      identify cases not linked to known clusters or cases and thus to obtain timely
      information on possible further contaminated vehicles distributed in Hesse, as
      well to describe the risk of secondary transmission among known cases. As of 2
      August 2011* [corrected], 56 cases of haemolytic uraemic syndrome (HUS) including
      two fatal cases, and 124 cases of STEC gastroenteritis meeting the national case
      definitions have been reported in Hesse. Among the 55 HUS and 81 STEC
      gastroenteritis cases thatmet the outbreak case definition, one HUS case and
      eight STEC gastroenteritis cases may have acquired their infection through
      secondary transmission. They include six possible transmissions within the
      family, two possible nosocomial and one possible laboratory transmission. Our
      results do not suggest an increased transmissibility of the outbreak strain
      compared to what is already known about E. coli O157 and other STEC serotypes.

PMID- 21871216
TI  - Household transmission of haemolytic uraemic syndrome associated with Escherichia
      coli O104:H4, south-western France, June 2011.
AB  - Following the outbreak of haemolytic uraemic syndrome (HUS) on June 2011 in south
      western France, household transmission due to Escherichia coli O104:H4 was
      suspected for two cases who developed symptoms 9 and 10 days after onset of
      symptoms of the index case. The analysis of exposures and of the incubation
      period is in favour of a secondary transmission within the family.
      Recommendations should be reinforced to prevent person-to-person transmission
      within households.

PMID- 21871217
TI  - Evidence of enzootic circulation of West Nile virus (Nea Santa-Greece-2010,
      lineage 2), Greece, May to July 2011.
AB  - A West Nile virus (WNV) surveillance network including sentinel chickens was
      deployed in Thessaloniki county, Greece, from May to July 2011. For the first
      time in summer 2011, a chicken WNV isolate from 6 July was molecularly
      identified. The partial NS3 sequence was identical to that of the Nea Santa
      Greece-2010 WNV lineage 2, detected in central Macedonia in 2010. This suggests
      that WNV is actively circulating in central Macedonia and that it may have
      overwintered in northern Greece.

PMID- 21871219
TI  - Enterohaemorrhagic Escherichia coli O104:H4: are we prepared now?

PMID- 21871218
TI  - Ongoing measles outbreak in Romania, 2011.
AB  - Since January 2011 Romania has been experiencing a measles outbreak with 2,072
      cases notified in 29 of the 42 Romanian districts. Most cases occurred in the
      north-western part of the country among unvaccinated children with the highest
      number of cases (893 cases) registered in children aged one to four years. This
      report underlines once more the need for additional measures targeting
      susceptible populations to achieve high vaccination coverage with two doses of
      measles-mumps-rubella vaccine.

PMID- 21871220
TI  - New European research project to respond to unexpected epidemic threats such as
      Escherichia coli.

PMID- 21871221
TI  - Unlinked anonymous testing to estimate HIV prevalence among pregnant women in
      Catalonia, Spain, 1994 to 2009.
AB  - This paper estimates the prevalence of human immunodeficiency virus (HIV)
      infections in women giving birth and women voluntarily terminating pregnancy over
      a period of sixteen years in Catalonia. Samples for HIV antibody detection were
      collected from the Neonatal Early Detection Programme for congenital metabolic
      diseases that covers 99% of infants born in Catalonia. The sampling method
      collected information of 50% of births every year and of all women attending
      three clinics for voluntary interruption of pregnancy. Using two sequential
      immunoassays we analysed unlinked anonymous blood spot samples from 549,689
      newborns between 1994 and 2009 and from 31,904 women who voluntarily interrupted
      pregnancy between 1999 and 2006. HIV prevalence among women giving birth
      decreased from 3.2 per 1,000 in 1994 to 1.7 per 1,000 in 2009 (p<0.01) and the
      mean age of infected mothers increased from 26 years in 1994 to 32 years in 2009
      (p=0.001). A decrease in HIV prevalence was also observed in women voluntarily
      terminating pregnancy, from 2.3 per 1,000 in 1999 to 1.0 per 1,000 in 2006
      (p<0.01). In contrast, estimated HIV prevalence in mothers born outside Spain
      increased from 2.2 per 1,000 in 2002 to 3 per 1,000 in 2009 (p<0.01) and their
      average age increased from 27 years in 2003 to 31 years in 2009 (p<0.01).

PMID- 21871222
TI  - Avian influenza A(H5N1) in humans: new insights from a line list of World Health
      Organization confirmed cases, September 2006 to August 2010.
AB  - The threat of avian influenza (AI) viruses to humans in Europe in 2005 prompted
      the Robert Koch Institute to establish a routine monitoring instrument condensing
      information on all human AI cases worldwide reported from the World Health
      Organization (WHO) and other sources into a line list for further analysis. The
      235 confirmed AI cases captured from September 2006 to August 2010 had a case
      fatality rate of 56% (132/235), ranging from 28% (27/98) in Egypt to 87% (71/82)
      in Indonesia. In a multivariable analysis, odds of dying increased by 33% with
      each day that passed from symptom onset until hospitalisation (OR: 1.33,
      p=0.002). In relation to children of 0-9 years, odds of fatal outcome were more
      than six times higher in 10-19 year-olds and 20-29 year-olds (OR: 6.06, 95% CI:
      1.89-19.48, p=0.002 and OR: 6.16, 95% CI: 2.05- 18.53, p=0.001, respectively),
      and nearly five times higher in patients of 30 years and older (OR: 4.71, 95% CI:
      1.56-14.27, p=0.006) irrespective of the country, which had notified WHO of the
      cases. The situation in Egypt was special in that case number and incidence in
      children were more than twice as high as in any other age group or country. With
      this study, we show that data from the public domain yield important
      epidemiological information on the global AI situation. This approach to
      establish a line list is time-consuming but a line list is a prerequisite to such
      evaluations. We thus would like to encourage the placing of a publicly accessible
      line list of anonymised human AI cases, e.g. directly by WHO. This might enhance
      our understanding of AI in humans and permit the rapid detection of changes in
      its epidemiology with implications for human health.

PMID- 21871223
TI  - Standardisation of multilocus variable-number tandem-repeat analysis (MLVA) for
      subtyping of Salmonella enterica serovar Enteritidis.
AB  - Salmonella enterica serovar (S.) Enteritidis is an important cause of food-borne
      infection in Europe and the United States. Further subtyping of isolates is
      necessary to support epidemiological data for the detection of outbreaks and
      identification of the vehicle of infection. Multilocus variable-number tandem
      repeat analysis (MLVA) is reportedly more discriminatory and produces data that
      are easier to share via databases than other molecular subtyping methods.
      However, lack of standardisation of the methodology and interpretive criteria for
      data analysis has meant that comparison of data between laboratories can be
      problematic. On the basis of MLVA profiles of 298 S. Enteritidis isolates
      received at the Health Protection Agency's Salmonella Reference Unit and sequence
      analysis of selected isolates, we propose a MLVA scheme for S. Enteritidis based
      on five loci (SENTR4, SENTR5, SENTR6, SENTR7 and SE-3) that have been selected
      from previously published S. Enteritidis MLVA schemes. A panel of reference
      strains has been developed that can be used by laboratories to normalise their
      raw fragment data to actual fragment sizes. We also provide recommendations for
      analysing and interpreting MLVA data. We urge laboratories to consider
      implementing these guidelines, thereby allowing direct comparison of data between
      laboratories irrespective of the platform used for fragment analysis, to
      facilitate international surveillance and investigation of international
      outbreaks.

PMID- 21871227
TI  - Outbreak due to a Klebsiella pneumoniae strain harbouring KPC-2 and VIM-1 in a
      German university hospital, July 2010 to January 2011.
AB  - We describe the epidemiology and characteristics of the pathogen and patients
      (n=7) associated with an outbreak of a carbapenem-resistant Klebsiella pneumoniae
      (CRKP) strain in a German university hospital from July 2010 to January 2011.
      Species identification and detection of carbapenem resistance were carried out
      using standard microbiological procedures. Carbapenemases were detected by
      phenotypic methods and specific polymerase chain reactions (PCRs). DNA
      fingerprinting profiles were performed with repetitive sequence-based PCR.
      Medical records of colonised or infected patients were retrospectively reviewed.
      Antibiotic resistance profiles, PCR-specific amplification products and
      genotyping demonstrated that the outbreak occurred because of the spread of a
      single CRKP clone harbouring both KPC-2 and VIM-1. Five of the seven patients had
      invasive infections with the CRKP strain; the deaths of four of them were
      directly related to the infection. Early implementation of infection control
      interventions brought about efficient containment of further cross-transmission.
      Rapid dissemination of carbapenemase-producing Enterobacteriaceae is a serious
      concern in patient care and is a problem that has emerged in western Europe.

PMID- 21871228
TI  - Human cases of West Nile Virus infection in north-eastern Italy, 15 June to 15
      November 2010.
AB  - In 2010, for the third consecutive year, human cases of West Nile virus (WNV)
      infection, including three confirmed cases of neuroinvasive disease and three
      confirmed cases of West Nile fever, were identified in north-eastern Italy. While
      in 2008 and 2009 all human cases of WNV disease were recorded in the south of the
      Veneto region, cases of WNV disease in 2010 additionally occurred in two
      relatively small northern areas of Veneto, located outside those with WNV
      circulation in the previous years. WNV IgG antibody prevalence in blood donors
      resident in Veneto was estimated as ranging from 3.2 per 1,000 in areas not
      affected by cases of WNV disease to 33.3 per 1,000 in a highly affected area of
      the Rovigo province. No further autochthonous human cases of WNV disease were
      notified in Italy in 2010. The recurrence of human cases of WNV infection for the
      third consecutive year strongly suggests WNV has become endemic in north-eastern
      Italy.

PMID- 21871229
TI  - Missed diagnosis of influenza B virus due to nucleoprotein sequence mutations,
      Singapore, April 2011.
AB  - A new influenza B variant was discovered in Singapore in April 2011 during
      diagnostic testing of a 3-year-old boy with respiratory symptoms. Influenza B
      virus was isolated from culture and confirmed by standard immunofluorescence
      testing, but was not detected by the routine, in-house influenza screening
      reverse-transcription polymerase chain reaction assay that targets the
      nucleoprotein (NP) gene. Subsequent sequencing investigations demonstrated that
      several other published assays targeting NP could also fail to detect this novel
      variant.

PMID- 21871230
TI  - Rabid dog illegally imported to France from Morocco, August 2011.
AB  - In August 2011, a case of canine rabies was notified to the French veterinary
      services. The dog was a three-month-old puppy illegally imported from Morocco
      that presented behavioural changes on 1 August and was admitted to a veterinary
      clinic on 6 August. It died the following day and the body was shortly sent to
      the national reference centre where rabies was laboratory-confirmed on 11 August.
      Contact tracing and post-exposure treatment were initiated immediately.

PMID- 21871231
TI  - Journal performance report for 2010.

PMID- 21871232
TI  - Child with right eye redness and swelling. Carotid-cavernous fistula (direct
      type).

PMID- 21871233
TI  - Infectious disease. Antiviral agents for the treatment and chemoprophylaxis of
      influenza.

PMID- 21871235
TI  - Change of shift. "Old".

PMID- 21871236
TI  - Annals of emergency medicine journal club. A tale of two steroids.

PMID- 21871237
TI  - Man with wrist injury after fall. Inverted lunate bone postreduction.

PMID- 21871238
TI  - Performance of single-use and reusable metal blades for emergency tracheal
      intubation in the out-of-hospital setting.

PMID- 21871239
TI  - Big brother could actually help quite easily: telementored "just-in-time"
      telesonography of the FAST over a smartphone.

PMID- 21871241
TI  - Dynamics of BNF-induced in vivo ethoxyresorufin-O-deethylase (EROD) activity
      during embryonic development of medaka (Oryzias latipes).
AB  - This study aimed to characterize quantitatively the temporal basal and induced
      ethoxyresorufin-O-deethylase (EROD) activity as indicator of cytochrome P4501A
      (CYP1A) function during embryonic development of medaka (Oryzias latipes). For
      this purpose, non-invasive methods over fluorescence images of the whole embryo
      (non-organ-specific [NOS] EROD activity) or specifically of the gallbladder
      (organ-specific [OS] EROD activity) were used. To induce this EROD activity,
      embryos were continuously exposed to beta-naphthoflavone (BNF; 0.005, 0.05, 0.5,
      5 MUg/L). Analytical chemistry suggested no signs of BNF dissipation. Mean
      fluorescence intensity values for EROD induction increased with BNF concentration
      throughout embryonic development. Significant increments in the NOS activity were
      seen from exposures to >= 0.5 MUg BNF/L as early as 2 days post-fertilization
      (dpf), and in the OS EROD activity as soon as the gallbladder was conspicuous
      (i.e. 4 dpf). Morphometric in vivo analysis of the gallbladder during embryonic
      development did not indicate significant dilation after BNF treatment suggesting
      normal hepatic bile formation. The conditions optimized in this study using
      intact embryos should allow the quantitation of EROD activity induced by specific
      chemicals, mixtures and environmental samples in terms of BNF-equivalents,
      offering a proper estimation of their potency. These results demonstrate the
      utility of medaka in a fish embryo test for a non-invasive CYP1A analysis
      expressed as EROD activity, fitting in the three R principles for the
      minimization of animal use in ecotoxicology evaluations and that are among the
      objectives of the European Community regulation for the Registration, Evaluation,
      Authorization and Restriction of Chemical substances (REACH).

PMID- 21871242
TI  - Effects of psychological treatment on recurrent abdominal pain in children - a
      meta-analysis.
AB  - Recurrent abdominal pain in children has a high prevalence, thought to be about
      10%. Untreated, there is a high risk that the symptoms become chronic and may
      lead in some cases to co-morbid mental disorders. Evidence-based treatments are
      therefore urgently needed. The objective of this study was to examine the
      effectiveness of psychological therapies for pain reduction in children with
      recurrent abdominal pain (RAP) by a meta-analysis of intervention studies. Ten
      controlled studies fulfilling minimum methodical criteria were included. The
      results of the analysis showed that psychological therapies, mainly cognitive
      behavioural, have a moderate effect on the reduction of pain in children with
      RAP. After analysing homogeneity and significance with the fixed effect model,
      the medium effect size, calculated with Hedges g, was 0.58 (sigma=0.16),
      demonstrating highly significant (p<.01) effects. The study showed that
      psychological therapies are effective in treating children with chronic abdominal
      pain. The empirical basis in this field needs to be broadened.

PMID- 21871243
TI  - Current advances in intraosseous infusion - a systematic review.
AB  - OBJECTIVES: To describe the advancement of Intraosseous (IO) infusion in the
      spectrum of resuscitative protocols and to provide a systematic review on
      currently used semi-automatic IO infusion devices. The specific question
      addressed was: "In patients undergoing resuscitation, does the use of semi
      automatic IO infusion devices compared to manual needles influence IO placement
      success rate, time for IO placement, and ease-of-use and user preference?"
      METHODS: The electronic databases PubMed and Embase were searched for articles
      published from 1997 to 2010 using the search terms ("intraosseous") AND ("needle"
      or "device" or "technique") AND ("infusion" or "injection" or "access"). The
      Internet search engine Google Scholar was searched using the search term
      "intraosseous infusion device" to identify articles published in electronic
      journals, books, and scientific websites. Articles were included only if they
      compared at least two types of semi-automatic devices, or compared one or more
      semi-automatic device with one or more manual needles. Reviews, editorials,
      surveys, and case reports were excluded. RESULTS: The search strategy yielded 179
      papers. Ten studies met full criteria for further review. Of these, two were LOE
      1 (randomized controlled trials), one was LOE 2 (non-randomized, concurrent
      controls), one was LOE 3 (retrospective controls), and six were LOE 5 (simulation
      based study). One of the six LOE 5 studies was a non-peer reviewed article.
      CONCLUSIONS: Only a few studies compared the performance of different types of IO
      infusion devices, most of them have a low level of evidence. These studies
      suggested a superiority of the battery-powered IO driver over manual needles, and
      other semi-automatic IO infuson devices.

PMID- 21871244
TI  - LAK cell therapy of AML: not to be lost in translation.
AB  - Expanding highly cytotoxic lymphokine activated natural killer cells and cytokine
      induced killer T cells by Good Manufacturing Practice-quality cultures is an
      important step toward effective use of those killer cells to treat acute myeloid
      leukemia patients receiving stem cell transplantation. Elucidating how those
      killer cells recognize leukemia stem cells will be the next challenge.

PMID- 21871245
TI  - Dynamics of cytomegalovirus (CMV) plasma DNAemia in initial and recurrent
      episodes of active CMV infection in the allogeneic stem cell transplantation
      setting: implications for designing preemptive antiviral therapy strategies.
AB  - Preemptive antiviral therapy strategies for active cytomegalovirus (CMV)
      infection occurring in allogeneic stem cell transplant recipients should be
      optimized to avoid overtreatment. The current study was aimed at determining
      whether the analysis of the kinetics of CMV DNA load in plasma may provide useful
      information for the therapeutic management of active CMV infection in this
      setting. A total of 59 consecutive patients were included in the study, of which
      40 (67.8%) developed 1 (n = 21) or more (n = 19) episodes of CMV DNAemia. The
      need for antiviral therapy for initial or secondary episodes of CMV DNAemia could
      not be predicted on the basis of the CMV DNA load value in the first plasma
      testing positive by polymerase chain reaction (PCR). In contrast, in the absence
      of antiviral therapy, an increase of >=3-fold between the baseline CMV DNA load
      and that measured a median of 6 days later discriminated between initial episodes
      eventually requiring antiviral treatment and those resolving spontaneously
      (sensitivity, 76.4%; specificity, 89.4%; positive predictive value, 86.6%;
      negative predictive value, 80.9%). This criterion was not useful for identifying
      recurrent episodes of CMV DNAemia that required antiviral therapy. The CMV
      doubling time and CMV DNA loads at the time of the first positive PCR and at
      initiation of preemptive therapy did not differ significantly between episodes
      that responded immediately to antiviral therapy from those showing a delayed
      response. The analysis of the dynamics of CMV DNA load in plasma in the absence
      of antiviral therapy allowed early recognition of episodes of CMV DNAemia that
      eventually needed to be treated, but did not permit prediction of the kinetics of
      CMV DNA clearance in response to antiviral therapy.

PMID- 21871246
TI  - Late relapses following high-dose autologous stem cell transplantation (HD-ASCT)
      for Hodgkin's lymphoma (HL) in the ABVD therapeutic era.
AB  - Salvage chemotherapy followed by high-dose autologous stem cell transplantation
      (HD-ASCT) is the standard of care for patients who have relapsed or refractory
      Hodgkin's lymphoma (HL). Few trials have had long-term follow-up post-HD-ASCT in
      the ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) era of treatment.
      We reviewed 95 consecutive patients who received HD-ASCT for relapsed or
      refractory HL following ABVD failure between 1990 and 2006 at the University of
      Rochester. Median follow-up for survivors was 8.2 years. All patients received HD
      ASCT following upfront ABVD (or equivalent) failure. At 5 years, overall survival
      (OS) and event-free survival (EFS) were 54% and 37%, respectively. In total, 54
      patients have died; 37 of these patients died directly of HL. Notably, there were
      19 deaths >3 years post-HD-ASCT and 13 of these late deaths are directly
      attributable to HL. Furthermore, there were 51 documented relapses, 9 of which
      occurred >3 years post-HD-ASCT. In contrast to other studies, we did not observe
      a plateau in EFS following transplantation. Patients appear to be at continuous
      risk of recurrence beyond 3 years after HD-ASCT. Our results emphasize the
      importance of long-term follow-up for both toxicity and recurrence, and have
      important implications in defining success of posttransplantation maintenance
      strategies.

PMID- 21871248
TI  - The Zollinger-Ellison syndrome: dangers and consequences of interrupting
      antisecretory treatment.
AB  - BACKGROUND & AIMS: Patients with Zollinger-Ellison syndrome (ZES) are treated by
      proton pump inhibitors (PPIs) to protect them from severe and potentially lethal
      peptic complications related to massive gastric acid hypersecretion. We report
      here on the dangerous consequences of interrupting PPI therapy. METHODS: We
      describe 2 ZES patients in whom interruption of PPI treatment for diagnostic
      evaluation generated severe health complications. RESULTS: Less than 48 hours
      after stopping PPIs, patient 1 developed multiple strictures of the esophagus
      caused by massive vomiting of gastric acid, and patient 2 presented with severe
      abdominal pain with intestinal microperforation from duodenal ulcers. Because of
      persistent gastrin stimulatory drive and because of the abolition of reflex
      protective defense mechanisms against gastric acid hypersecretion during PPI
      treatment, patients with ZES under PPI therapy are exposed to severe peptic
      complications when facing rebound acid secretion at the interruption of their
      antisecretory treatment. CONCLUSIONS: PPI treatment interruption has dangerous
      consequences, and PPI therapy always should be maintained in patients known or
      suspected of ZES. Diagnostic evaluations should be performed under PPI
      protection.

PMID- 21871247
TI  - Similarities and differences between diabetic and idiopathic gastroparesis.
AB  - BACKGROUND & AIMS: Gastroparesis can be diabetic or idiopathic, yet little is
      known about differences in their presentation. We compared clinical
      characteristics, symptoms, and gastric emptying in patients with type 1 or type 2
      diabetic (DG) or idiopathic (IG) gastroparesis. METHODS: We analyzed data from
      416 patients with gastroparesis who were enrolled in the National Institute of
      Diabetes and Digestive and Kidney Diseases Gastroparesis Registry; 254 had IG
      (most were female and white), and 137 had DG (78 had type 1 and 59 had type 2).
      Registry data included detailed histories, physical examinations, results from
      gastric emptying scintigraphy, and responses to validated symptom questionnaires.
      RESULTS: Patients with type 2 diabetes mellitus (DM) were an average of 13 years
      older at the onset of symptoms of gastroparesis and heavier than patients with
      IG. Patients with type 1 DM had more hospitalizations in the past year than
      patients with IG. Symptoms that prompted evaluation more often included vomiting
      for DG and abdominal pain for IG. Patients with DG had more severe retching and
      vomiting than those with IG, whereas patients with IG had more severe early
      satiety and postprandial fullness subscores. Compared with IG, gastric retention
      was greater in patients with type 1 DM. More than 50% of patients with type 1 DM
      had severe retention (>35% at 4 hours); they took prokinetic agents more
      frequently and were more likely to receive gastric electric stimulation.
      CONCLUSIONS: There are similarities and differences in clinical characteristics
      of DG and IG. Gastroparesis is a heterogeneous disorder; its etiology affects
      symptoms and severity. Long-term studies are needed to determine whether the
      differences in symptoms and gastric emptying affect progression and treatment
      responses.

PMID- 21871250
TI  - Diagnosis, comorbidities, and management of irritable bowel syndrome in patients
      in a large health maintenance organization.
AB  - BACKGROUND & AIMS: Irritable bowel syndrome (IBS) imposes significant clinical
      and economic burdens. We aimed to characterize practice patterns for patients
      with IBS in a large health maintenance organization, analyzing point of
      diagnosis, testing, comorbidities, and treatment. METHODS: Members of Kaiser
      Permanente Northern California who were diagnosed with IBS were matched to
      controls by age, sex, and period of enrollment. We compared rates of testing,
      comorbidities, and interventions. RESULTS: From 1995-2005, IBS was diagnosed in
      141,295 patients (mean age, 46 years; standard deviation, 17 years; 74% female).
      Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower
      endoscopy did not usually precede IBS diagnosis. Patients with IBS were more
      likely than controls to have blood, stool, endoscopic, and radiologic tests and
      to undergo abdominal or pelvic operations (odds ratios, 1.5-10.7; all P < .0001).
      Only 2.7% were tested for celiac disease, and only 1.8% were eventually diagnosed
      with inflammatory bowel disease. Chronic pain syndromes, anxiety, and depression
      were more common among IBS patients than among controls (odds ratios, 2.7-4.6;
      all P < .0001). Many patients with IBS were treated with anxiolytics (61%) and
      antidepressants (55%). Endoscopic and radiologic testing was most strongly
      associated with having IBS diagnosed by a gastroenterologist. Psychotropic
      medication use was most strongly associated with female sex. CONCLUSIONS: In a
      large, managed care cohort, most diagnoses of IBS were made by generalists, often
      without endoscopic evaluation. Patients with IBS had consistently higher rates of
      testing, chronic pain syndromes, psychiatric comorbidity, and operations than
      controls. Most patients with IBS were treated with psychiatric medications.

PMID- 21871251
TI  - Trigger-specific ion-channel mechanisms, risk factors, and response to therapy in
      type 1 long QT syndrome.
AB  - BACKGROUND: Arrhythmic events in long-QT syndrome type 1 (LQT1) may be associated
      with exercise, acute arousal, or rest/sleep. OBJECTIVES: We aimed to identify
      trigger-specific risk factors for cardiac events in patients with LQT1. METHODS:
      The study population comprised 721 genetically confirmed patients with LQT1 from
      the US portion of the International LQTS Registry. Multivariate analysis was used
      to assess the independent contribution of prespecified clinical and mutation
      specific factors to the development of a first reported triggered event,
      associated with exercise, arousal, or sleep/rest. RESULTS: Cardiac events
      occurred in 221 study patients, of whom 121 (55%) were associated with exercise,
      30 (14%) with arousal, 47 (21%) with sleep/rest, and 23 (10%) with other
      triggers. Multivariate analysis showed that males <13 years had a 2.8-fold (P <
      .001) increase in the risk for exercise-triggered events whereas females >=13
      years showed a 3.5-fold (P = .002) increase in the risk for sleep/rest nonarousal
      events. Cytoplasmic-loop mutations within the transmembrane region, involved in
      adrenergic channel regulation, were associated with the increased risk for both
      exercise- and arousal-triggered events (hazard ratio = 6.19 [P < .001] and 4.99
      [P < .001], respectively) but were not associated with events during sleep/rest
      (hazard ratio = 0.72; P = .46). Beta-blocker therapy was associated with a
      pronounced 78% (P < .001) reduction in the risk for exercise-triggered events but
      did not have a significant effect on events associated with arousal or
      sleep/rest. CONCLUSIONS: In patients with LQT1, cardiac events triggered by
      exercise, arousal, or rest/sleep are associated with distinctive risk factors and
      response to medical therapy. These findings can be used for improved
      recommendations for lifestyle modifications and therapeutic management in this
      population.

PMID- 21871249
TI  - Treating Clostridium difficile infection with fecal microbiota transplantation.
AB  - Clostridium difficile infection is increasing in incidence, severity, and
      mortality. Treatment options are limited and appear to be losing efficacy.
      Recurrent disease is especially challenging; extended treatment with oral
      vancomycin is becoming increasingly common but is expensive. Fecal microbiota
      transplantation is safe, inexpensive, and effective; according to case and small
      series reports, about 90% of patients are cured. We discuss the rationale,
      methods, and use of fecal microbiota transplantation.

PMID- 21871252
TI  - Successful treatment of myocardial infarction by aortic sinus thrombosis.
AB  - This case report concerns a 59-year-old man with acute myocardial infarction
      associated with a giant organized thrombus occupying the right sinus of Valsalva
      that developed into chest pain and bradycardia. Magnetic resonance imaging showed
      low intensity in both T1-weighted and T2-weighted images, indicating that the
      mass was a thrombus. A direct approach involving grafting effectively resolved
      the embolization and myocardial ischemia, even during the subacute period.

PMID- 21871253
TI  - Comprehensive dynamic aortic and cardiac analysis by 256-slice computed
      tomography in type A dissection.
AB  - The faster scanning speed of 256-slice computed tomographic scanners has enabled
      electrocardiographic-gated imaging of the entire thoraco-abdominal aorta in
      several seconds. Electrocardiographic-gated acquisition allows for image
      reconstruction in any desired phase of the cardiac cycle, as well as dynamic
      assessment by looping the different reconstruction phases. We describe the
      application of 256-slice computed tomography in a patient with Marfan syndrome
      and acute type A aortic dissection. A comprehensive static and dynamic aorto
      cardiac analysis was performed from a single scan, including the aortic
      dissection, aortic valve prosthesis, and coronary arteries.

PMID- 21871254
TI  - Wrapping of the ascending aorta in acute type A retrograde aortic dissection.
AB  - We describe off-pump wrapping of the ascending aorta in 3 high-risk patients with
      acute type A aortic dissection when the primary intimal tear was not located in
      the ascending aorta and in the absence of aortic insufficiency. A Teflon plaque
      (Bard Inc, Murray Hill, NJ) was tailored to tightly wrap the aorta from the
      coronary ostia to the innominate artery. The mean age of the patients was 80.3
      years. All patients were at high risk for conventional surgery. A postoperative
      computed tomographic scan showed a reapplication of the intimal flap and
      containment of the false lumen in the reinforced ascending aorta in all patients.

PMID- 21871255
TI  - A rare case of partial anomalous pulmonary venous return to azygos vein without
      direct connection to great cardiac vessels.
AB  - A 17-year-old girl visited our hospital for an operation to correct a partial
      anomalous pulmonary venous return. All the right-side pulmonary veins returned to
      the azygos vein, which had no connection to the cardiac chamber through the great
      venous system, such as the superior or inferior vena cava. The azygos vein lacked
      a normal azygos arch and was connected by multiple connections only to the
      paravertebral plexus. For the surgical correction, a pericardiostomy was created
      in the right posterior pericardial wall and azygos vein which was divided at the
      diaphragm level and was anastomosed to the left atriotomy area through the
      pericardiostomy site.

PMID- 21871256
TI  - Limb salvage surgery in the excision of a massive fibromatosis.
AB  - Fibromatosis is a rare fibroproliferative disorder with a tendency for local
      infiltrative and destructive growth. Local recurrence is frequent, despite
      apparent complete resection after radical excision. We present a case of a 22
      year-old woman with massive recurrent thoracic fibromatosis extending into the
      neck and impairing the function of her right upper limb. This required a
      multidisciplinary approach to surgery to salvage the limb. The case highlights
      the fact that while every attempt should be made to achieve negative histologic
      margins, local recurrence is not uncommon. Therefore, if fibromatosis occurs
      adjacent to or involves vital structures, these should not be sacrificed to
      achieve negative margins. Function and structure preserving procedures are
      important as the primary goal, if not even more important.

PMID- 21871257
TI  - An atypical thrombus in the inflow cannula of the HeartWare left ventricular
      assist device.

PMID- 21871258
TI  - Three-dimensional imaging of pectus excavatum mesh repair 7 years after
      performing Robicsek technique.

PMID- 21871259
TI  - Composite root replacement at the level of the aortoventricular junction.
AB  - Composite root replacement has become the gold standard treatment for many root
      pathologies. The results are excellent; however, postoperative heart block does
      occur. We have adopted a modification of the conventional suture placement
      techniques aiming to reduce this complication. By skeletonizing the root and
      passing the valve sutures transmurally at the level of the anatomic
      aortoventricular junction rather than through the surgical annulus we give wide
      berth to the conduction system. This also facilitates placement of a hemostatic
      running suture around the prosthesis, if desired. We have seen a reduction in
      heart block requiring pacemaker implantation without prolongation of bypass or
      cross-clamp times.

PMID- 21871260
TI  - Should the financial link between industry and physician consultants be severed?

PMID- 21871261
TI  - Invited commentary.

PMID- 21871262
TI  - Invited commentary.

PMID- 21871263
TI  - Invited commentary.

PMID- 21871264
TI  - Integrating coronary anastomotic connectors and robotics toward a totally
      endoscopic beating heart approach: review of 120 cases.
AB  - BACKGROUND: Endoscopic coronary bypass has been a difficult procedure to perform.
      The recent introduction of the Intuitive EndoWrist stabilizer (Intuitive
      Surgical, Sunnyvale, CA) has facilitated this procedure robotically on the
      beating heart. The addition of anastomotic connectors allows a significant
      improvement in the execution of this technically demanding procedure. We report
      on our first 120 cases of totally endoscopic, beating heart connector coronary
      artery bypass grafting integrating these technologies. METHODS: From January 2008
      to April 2010, 120 patients (age range 43 to 86 years, 72% male) underwent either
      single or multivessel all arterial, totally endoscopic coronary artery bypass
      grafting using the da Vinci robot with the aid of the Flex A distal anastomotic
      device (Cardica, Redwood City, CA). Patients with multivessel disease involving
      branches of the right coronary and circumflex arteries underwent hybrid
      revascularization with stents. Early and midterm clinical outcomes were evaluated
      for all patients. Eighty-five internal mammary artery grafts in 68 patients were
      evaluated at a mean of 4 months using multidetector computed tomography and
      formal angiography (in 18 hybrid patients). RESULTS: Mean hospital stay was 3.3+/
      2.4 days. There was 1 postoperative death (the same patient had a stroke
      secondary to carotid disease), and 1 postoperative myocardial infarction. Two
      patients were converted to minithoracotomy and 1 patient was converted to
      sternotomy. One patient required cardiopulmonary bypass support through the
      femoral cannulation during the procedure. Mean intraoperative transit time flow
      in all the internal mammary artery grafts was 76 cc/minute+/-43, and pulsatility
      index of 1.5+/-0.5. Of the 85 grafts evaluated angiographically, 80 were patent
      at a mean of 4 months (94.1%). CONCLUSIONS: Totally endoscopic beating heart
      connector coronary bypass using the da Vinci robot with the Flex A anastomotic
      device is a safe and reproducible procedure. A significant learning curve is
      involved and experience with anastomotic devices in the open setting is
      necessary. Long-term follow-up of graft patency and patient outcomes is
      warranted.

PMID- 21871265
TI  - Invited commentary.

PMID- 21871267
TI  - Enhanced vascularization by controlled release of platelet-rich plasma
      impregnated in biodegradable gelatin hydrogel.
AB  - BACKGROUND: Platelet-rich plasma (PRP) contains numerous growth factors that have
      angiogenic activities. However, the PRP-induced angiogenesis is limited by the
      short half-life period of growth factors. A new drug delivery system of
      biodegradable gelatin hydrogel was designed to achieve the controlled release of
      growth factors in PRP. The purpose of this study is to demonstrate the
      therapeutic efficacy of slow-release of PRP in the inducing of angiogenesis for
      critical ischemia. METHODS: The PRP was prepared from the whole blood of inbred
      rats. Thirty-two rats underwent excision of the left femoral artery and its
      branches to create critical limb ischemia. The rats were randomized into four
      groups (n=8 each): no treatment (control), intramuscular injection of platelet
      poor plasma (PPP), PRP only, or a combination of PRP and gelatin hydrogel
      (PRP+Gel). Four weeks after the treatment, angiogenesis was evaluated by laser
      doppler, microangiogram, and immunohistology. RESULTS: The resultant number of
      platelets for PRP was higher than that of PPP (p<0.01). The concentrations of
      vascular endothelial growth factor, transforming growth factor-beta1, and
      platelet-derived growth factor-BB were significantly higher in PRP animals than
      in PPP (p<0.01). Although the PRP group improved tissue blood flow (82.7%+/-6.2%)
      compared with the control group or PPP group (69.6+/-12.2 or 72.2+/-11.8%,
      p<0.05), the improvement of blood flow in the PRP+Gel group was significantly
      better (95.1%+/-8.0%, p<0.05) than in the PRP group. Angiographic score in the
      PRP+Gel group was significantly higher than that in the control, PPP, and PRP
      groups (8.6+/-2.1 versus 3.8+/-0.8, 3.7+/-0.6, and 5.6+/-1.5, respectively;
      p<0.01). Capillary density also increased immunohistologically in the PRP+Gel
      group when compared with the control, PPP, and PRP groups (p<0.01). CONCLUSIONS:
      A controlled release system of PRP was effective in inducing angiogenesis for
      critical ischemia. The biodegradable gelatin hydrogel incorporating PRP as
      applicable could possibly be used to treat for patients with ischemic
      cardiomyopathy.

PMID- 21871266
TI  - Thromboxane-induced contractile response of human coronary arterioles is
      diminished after cardioplegic arrest.
AB  - BACKGROUND: We investigated the contractile response of human coronary
      microvasculature to thromboxane A-2 (TXA-2), with and without the blockade of TXA
      2 receptors or the inhibition of phospholipase-C (PLC) or of protein kinase C
      alpha (PKC-alpha) in the human coronary microvasculature before and after
      cardioplegia, followed by reperfusion (CP/Rep). Protein/gene expression and
      localization of TXA-2 receptors, TXA-2 synthase, PLC, and other TXA-2-related
      proteins was also examined. METHODS: Right atrial tissue was harvested before and
      after cold blood cardioplegia, followed by about 10 minutes of reperfusion, from
      28 patients undergoing cardiac operations. Coronary arterioles (90 to 170 MUm in
      diameter) were dissected from the harvested tissue. RESULTS: The post-CP/Rep
      contractile response of coronary arterioles to TXA-2 analog U-46619 was
      significantly impaired vs pre-CP/Rep (p<0.05). The TXA-2 receptor antagonist SQ
      29548 (10(-6) M) prevented the contractile response to U-46619 (p<0.05).
      Pretreatment with the PLC inhibitor U73122 (10(-6) M) significantly inhibited the
      U-46619-induced contractile response (p<0.05). Administration of the PKC-alpha
      inhibitor safingol failed to affect U-46619-induced contraction. Total protein
      levels and gene expression of TXA-2 receptors, TXA-2 synthase, PLC-beta3, phospho
      PLC-beta3, PLC-gamma1, and phospho-PLC-gamma1 were not altered after CP/Rep.
      Confocal microscopy showed no significant differences in the expression of TXA-2
      receptors or PLC-beta3 in the microcirculation. TXA-2 receptors and PLC-beta3
      were both present in smooth muscle and endothelium. CONCLUSIONS: Cardioplegia/Rep
      decreases the contractile response of human coronary arterioles to TXA-2 soon
      after cardiac operations. The contractile response to the TXA-2 analog U-46619 is
      through activation of TXA-2 receptors and PLC.

PMID- 21871268
TI  - Expression and function of endothelial nitric oxide synthase messenger RNA and
      protein are higher in internal mammary than in radial arteries.
AB  - BACKGROUND: The internal mammary artery (IMA) has a better long-term patency rate
      than the radial artery (RA), but the underlying molecular mechanisms are unclear.
      We compared endothelial nitric oxide synthase (eNOS) and related NO release in
      these two arteries. METHODS: Real-time polymerase chain reaction was used to
      quantify eNOS messenger RNA (mRNA) expression level in the endothelial cells of
      IMAs and RAs. eNOS protein localization was determined by immunohistochemistry.
      NO release from the endothelium of IMAs and RAs was directly measured by an
      electrochemical method using a membrane-type NO-sensitive electrode. RESULTS:
      Endothelial nitric oxide synthase mRNA expression level was significantly higher
      in the endothelial cells of IMAs than in RAs (1.03+/-0.19 vs 0.53+/-0.09, n=7,
      p<0.05), but was similar in the whole vascular tissue. eNOS protein
      immunoreactivity was higher in the endothelial cells of IMAs than in RAs. NO
      release at both levels in IMAs was significantly greater than in RAs (basal:
      17.5+/-1.9 vs 10.2+/-0.7 nM, n=11 each, p=0.003; stimulated with bradykinin -7
      log M: 31.5+/-3.6 vs 14.3+/-5.3 nM, n=6 each, p=0.02). CONCLUSIONS: Endothelial
      cells in the IMA express higher levels of eNOS mRNA and protein than those in the
      RA, which is linked with higher release of NO. These findings may be related to
      the superior long-term patency rate of the IMA vs the RA. This study also
      provides some basic genetic information for grafting arteries.

PMID- 21871269
TI  - Long-term survival and quality of life justify cardiac surgery in the very
      elderly patient.
AB  - BACKGROUND: Elderly patients are often discouraged from undergoing cardiac
      surgery procedures owing to the perception of high mortality and poor functional
      outcomes. This study evaluates long-term survival and quality of life after
      cardiac surgery in octogenarian and nonagenarian patients. METHODS: We identified
      a 459 patient cohort greater than 80 years of age who underwent elective cardiac
      surgery at our institution from 1994 to 1999. Survival was assessed with Kaplan
      Meier analysis and compared with an age-matched and sex-matched population
      cohort. Among survivors, quality of life was assessed 8 years postoperatively
      using the Medical Outcomes Study Short Form 12 Health Survey, version 2. Risk
      factors for mortality were identified with Cox regression. RESULTS: Operative
      mortality was 4.1%. Actuarial postoperative 5-year and 10-year survival was 53%
      and 27%, respectively. When compared with age- and sex-matched general population
      data, relative survival (excluding operative deaths) was 90.4% at 5 years and
      78.7% at 10 years. Risk factors for late mortality included age greater than 85,
      male sex, low body mass index, renal failure, and postoperative respiratory
      failure. Survivors' median quality of life mental health score was higher (55.2
      versus 48.9; p<0.05) and physical health score was equivalent (39.3 versus 39.8;
      p=0.66) to the general elderly population. CONCLUSIONS: Cardiac surgery in the
      very elderly patient can be performed with low operative mortality, excellent
      long-term survival, and postoperative quality of life exceeding that of the
      general elderly population.

PMID- 21871270
TI  - Triglycidyl amine crosslinking combined with ethanol inhibits bioprosthetic heart
      valve calcification.
AB  - BACKGROUND: One of the most important factors responsible for the calcific
      failure of bioprosthetic heart valves is glutaraldehyde crosslinking. Ethanol
      (EtOH) incubation after glutaraldehyde crosslinking has previously been reported
      to confer anticalcification efficacy for bioprostheses. The present studies
      investigated the anticalcification efficacy in vivo of the novel crosslinking
      agent, triglycidyl amine (TGA), with or without EtOH incubation, in comparison
      with glutaraldehyde. METHODS: The TGA crosslinking (+/-EtOH) was used to prepare
      porcine aortic valves for both rat subdermal implants and sheep mitral valve
      replacements, for comparisons with glutaraldehyde-fixed controls. Thermal
      denaturation temperature, an index of crosslinking, cholesterol extraction, and
      hydrodynamic properties were quantified. Explant endpoints included quantitative
      and morphologic assessment of calcification. RESULTS: Thermal denaturation
      temperatures after TGA were intermediate between unfixed and glutaraldehyde
      fixed. EtOH incubation resulted in almost complete extraction of cholesterol from
      TGA or glutaraldehyde-fixed cusps. Rat subdermal explants (90 days) demonstrated
      that TGA-EtOH resulted in a significantly greater level of inhibition of
      calcification than other conditions. Thus, TGA-ethanol stent mounted porcine
      aortic valve bioprostheses were fabricated for comparisons with glutaraldehyde
      pretreated controls. In hydrodynamic studies, TGA-EtOH bioprostheses had lower
      pressure gradients than glutaraldehyde-fixed. The TGA-ethanol bioprostheses used
      as mitral valve replacements in juvenile sheep (150 days) demonstrated
      significantly lower calcium levels in both explanted porcine aortic cusp and
      aortic wall samples compared with glutaraldehyde-fixed controls. However, TGA
      EtOH sheep explants also demonstrated isolated calcific nodules and intracuspal
      hematomas. CONCLUSIONS: The TGA-EtOH pretreatment of porcine aortic valves
      confers significant calcification resistance in both rat subdermal and sheep
      circulatory implants, but with associated structural instability.

PMID- 21871271
TI  - Operative risks and survival in veterans with severe aortic stenosis: surgery
      versus medical therapy.
AB  - BACKGROUND: Transcatheter aortic valves were developed as an alternative to
      surgery for the one third to two thirds of patients with severe aortic stenosis
      who do not undergo aortic valve replacement. In this study, we examined reasons
      for medical management of aortic stenosis in relation to operative risks and
      outcomes for veterans with and without valve replacement. METHODS: The
      echocardiography database was screened from 2000 to 2007 for severe aortic
      stenosis. The Society of Thoracic Surgeons risk scores and survival were
      determined for patients with and without aortic valve replacement. RESULTS: Of
      132 severe aortic stenosis patients included, 42% were medically managed.
      Predicted operative mortality risk was lower for surgical patients than for
      medical patients (4.5%+/-4.2% versus 6.8%+/-5.1%, p=0.002). Overall, the most
      common reason for medical management of aortic stenosis was assumption that the
      patient was high risk for surgery (30.4%). The surgery group had significantly
      higher median survival (92.2 versus 32.4 months) and 5-year survival (71% versus
      37%, p<0.001) than the medical group. Cardiac surgery was not consulted in 61% of
      medically managed patients, of whom only 18% had Society of Thoracic Surgeons
      risk score of 10 or greater. Aortic valve replacement was an independent
      predictor of lower mortality (hazard ratio 0.43, p=0.008). CONCLUSIONS: Although
      operative risk was higher among patients who did not undergo surgery, most were
      not the 10% or greater required for transcatheter valves. Given the significantly
      lower survival with medical therapy, aortic valve replacement should be carefully
      considered for most severe aortic stenosis patients whereas transcatheter aortic
      valves should be reserved for patients with high operative risks.

PMID- 21871272
TI  - Proximal thoracic aortic replacement for aneurysmal disease using the freestyle
      stentless bioprosthesis: a 10-year experience.
AB  - BACKGROUND: Porcine bioprosthesis (bioroots) are an attractive surgical strategy
      for ascending aorta and arch replacement. This study evaluated the perioperative
      and late outcomes using this strategy for proximal aortic aneurysmal disease.
      METHODS: Between March 1998 and November 2009, 170 patients (40% women; median
      age, 70 years) underwent proximal thoracic aortic replacement using the Freestyle
      (Medtronics Inc, Minneapolis, MN) bioroot, with graft extension in 149 (87.6%).
      Aneurysmal etiology included degenerative-atherosclerotic (91.2%), acute
      dissection (5.3%), and chronic dissection (3.5%); 78% had greater than moderate
      aortic insufficiency. Surgical procedures were bioroot alone or with aortoplasty
      (12.3%), bioroot with ascending aortic graft (38.2%), bioroot with hemiarch graft
      (44.1%), and bioroot with total arch (5.3%). Hypothermic circulatory arrest was
      required in 49%. RESULTS: The 30-day mortality was 4.7% (n=8). The overall
      complication rate was 58% (n=100), including stroke (6.5%), renal failure (9.2%),
      respiratory failure (25.9%), and postoperative bleeding (7.6%). Mean
      hospitalization was 10.5+/-7.3 days; 38 were discharged to a rehabilitation
      facility (23.5%). Predictors of 30-day/hospital death were coronary artery
      disease (p=0.0003), renal insufficiency (p<0.0001), emergent/urgent procedure
      (p=0.02), and hypothermic circulatory arrest (p=0.002). The 1-year, 5-year, and
      10-year survivals were 90%, 80%, and 35% respectively. Freedom from endocarditis
      and reoperation was 96% at 1 year and 94% and 95% at 5 years, respectively.
      CONCLUSIONS: Proximal thoracic aortic replacement using a porcine bioroot as part
      of the repair can be achieved with low perioperative mortality and acceptable
      late survival in a predominantly elderly population.

PMID- 21871273
TI  - Small prosthesis size in aortic valve replacement does not affect mortality.
AB  - BACKGROUND: Small prosthesis size has been associated with poorer postoperative
      outcomes in aortic valve replacement (AVR). We hypothesized that the use of small
      aortic valve (AV) prostheses does not independently increase operative mortality
      following AVR, but that mortality may instead be related to comorbidities.
      METHODS: We examined the mortality among 4,621 patients who underwent primary AVR
      operations at 13 different statewide centers from 2003 to 2008. Patients were
      stratified by prosthesis size into groups with small (<=21 mm, n=1,810) and
      standard AV prostheses (>=23 mm, n=2,811). The effect of prosthesis size on
      outcomes was evaluated with univariate and multivariable regression analyses.
      RESULTS: Operative mortality among patients undergoing primary AVR operations was
      3.7%. Among isolated operations, small AV prostheses were implanted in more
      females (79.9% vs 21.0%, p<0.001) and older patients (68.9+/-12.3 years vs 63.8+/
      13.9 years, p<0.001) than were standard-size AV prostheses, and carried a higher
      predicted risk of mortality according to the Society of Thoracic Surgeons
      Predicted Risk of Mortality Score (3.1 [interquartile range, 3.0] versus 2.2
      [2.0], p<0.001) than did standard-size AV prostheses. Small AV prostheses
      incurred more major complications (19.5% vs 15.7%, p=0.01), a greater mortality
      (3.9% vs 2.3%, p=0.03), a longer postoperative length of stay (6.0 [3.0] vs 5.0
      [3.0] days, p<0.001), and higher total costs ($29,738 [18,196] vs $26,679
      [14,890], p<0.001) than did standard AV prostheses. However, when analyzed with
      multivariate regression, small AV prosthesis size and female gender were not
      independent predictors of operative mortality, whereas advanced age,
      cardiopulmonary bypass time, and aortic annular enlargement were important
      predictors of operative mortality. CONCLUSIONS: Small aortic valve prosthesis
      size does not independently increase operative mortality following primary AVR.
      Increased morbidity and mortality among patients undergoing the implantation of
      small AV prostheses is related to the confounding effects of preoperative and
      operative risk factors. Annular enlargement may not always reduce mortality.

PMID- 21871274
TI  - Outcomes after total aortic arch replacement with right axillary artery
      cannulation and a presewn multibranched graft.
AB  - BACKGROUND: Several techniques are available for aortic arch replacement. We
      evaluated our experience with total aortic arch replacement using a presewn
      multibranched graft and right axillary artery cannulation for brain perfusion.
      METHODS: Between 2002 and 2010, 88 patients (mean age, 61.5+/-14.6 years)
      underwent total aortic arch replacement by midline sternotomy (27 patients) or
      bilateral anterior thoracotomy (61 patients). During a brief period of deep
      hypothermic circulatory arrest (DHCA) (mean duration, 11.0+/-7.8 minutes), the
      brachiocephalic arteries were detached from the aorta and clamped. Cerebral
      perfusion through the right axillary artery was then initiated while the arteries
      were sequentially attached to the branches of the presewn graft (mean duration:
      40.4+/-9.8 minutes). The ascending aorta and entire arch were replaced in all
      patients, combined with varying lengths of the descending aorta. RESULTS: The 30
      day mortality rate was 5.7%. Stroke occurred in 3.4%, spinal cord ischemic injury
      in 3.4% (1 paraplegia, 2 paraparesis), and new-onset renal failure requiring
      dialysis in 3.4% of patients. The 5-year survival rate was 70.7%+/-5.5%. All
      graft branches remained patent during imaging follow-up (mean duration, 2.6+/-2.2
      years). Six patients required reoperation on the graft or contiguous aorta after
      the initial repair, but no reoperations were required on the aortic arch or its
      branches. The 5-year rate of freedom from reoperation was 90.4%+/-4.0%.
      CONCLUSIONS: The use of a presewn multibranched graft and hypothermic brain
      perfusion through the right axillary artery is a safe method for replacement of
      the aortic arch, resulting in a low incidence of neurologic complications and
      favorable durability and patency.

PMID- 21871275
TI  - Results of reoperation on the aortic root and the ascending aorta.
AB  - BACKGROUND: Reoperations on the aortic root and the ascending aorta after
      previous aortic valve and proximal aortic surgery are increasingly frequent and
      highly demanding. The scarce comparability of the published series and the
      heterogeneity of clinical pictures contribute to the challenges of this subgroup.
      METHODS: Forty-one patients (2004 to 2010) who were reoperated on the aortic root
      and the ascending aorta for aneurysmal, pseudoaneurysmal, or infectious disease
      were retrospectively analyzed from a prospectively filled-in database. RESULTS:
      Mean logistic European system for cardiac operative risk evaluation was 29.8%. At
      index reoperation, procedures were classic Bentall (51%), prosthesis-sparing
      operation (17%), supracoronary ascending aortic replacement plus aortic valve
      replacement-repair (22%), and root replacement using valved homografts (9.7%).
      Distally, the operation involved the arch in 51% of cases (17 hemiarch
      replacement, 4 total transverse arch, 3 elephant trunk). Operative mortality was
      12% and rate of major operative morbidity was 17%. At a mean 26-months follow-up,
      the patients surviving the operation had a good survival and functional class.
      The rate of adverse events during the follow-up was acceptable. CONCLUSIONS:
      Reoperations on the aortic root-ascending aorta in the elective patients have
      respectable operative mortality-morbidity despite the high-risk profile, and are
      justified by the excellent follow-up survival. The mortality can be diminished by
      integrated surgical strategies and optimal myocardial protection. Our findings
      encourage complete resection of borderline dilated ascending aortic-root tissue
      at primary and redo operation.

PMID- 21871276
TI  - Invited commentary.

PMID- 21871277
TI  - Creation of a quantitative recipient risk index for mortality prediction after
      cardiac transplantation (IMPACT).
AB  - BACKGROUND: No recipient risk index exists predicting short-term mortality after
      orthotopic heart transplantation (OHT). We utilized United Network for Organ
      Sharing (UNOS) data to develop a novel quantitative recipient risk score for use
      in OHT. METHODS: A prospectively collected open cohort of 21,378 primary OHT
      patients (1997 to 2008) was randomly divided into subgroups. The training cohort
      (n=17,079) was used for score derivation and the test cohort (n=4,299) was used
      for independent validation. Recipient specific variables associated with 1-year
      mortality (exploratory p value<0.2) were incorporated stepwise into a
      multivariable logistic regression model. The final model contained variables
      which maximized explanatory power (assessed by pseudo R2, area under the curve,
      and likelihood-ratio test). A risk index was created by apportioning points
      approximating the relative impact of variables on 1-year mortality. The Kaplan
      Meier method was used to assess impact of risk score on short-term survival.
      RESULTS: The 50-point scoring system incorporated 12 recipient specific
      variables. Derivation and validation cohort scores ranged from 0 to 33 and 0 to
      27, respectively (mean 6.1+/-3.7 and 6.1+/-3.7). Each point increased the odds of
      1-year death by 14% in the derivation cohort (odds ratio 1.14 [1.13 to 1.15],
      p<0.001) and 15% in the validation cohort (odds ratio 1.15 [1.12 to 1.17],
      p<0001). One-year survivals in the validation cohort (by increments of 3 points)
      were the following: 0 to 2 (92.5%); 3 to 5 (89.9%); 7 to 9 (86.3%); and 10 or
      greater (74.9%); p<0.001. Patients transplanted with risk scores of 20 or higher
      had 1-year mortality rates greater than 50%. CONCLUSIONS: We present a novel
      internally validated OHT recipient risk score, which is highly predictive of 1
      year mortality. This risk index may prove valuable for patient prognosis, organ
      allocation, and research stratification in OHT.

PMID- 21871278
TI  - Should heart transplant recipients with early graft failure be considered for
      retransplantation?
AB  - BACKGROUND: The purpose of this study was to determine if orthotopic heart
      transplantation performed within 90 days of an initial heart transplant (re-Tx)
      should be a contraindication to retransplantation based on inferior outcomes when
      compared with primary orthotopic heart transplantation recipients (control).
      METHODS: De-identified data were obtained from the United Network for Organ
      Sharing. The study population included all adult heart transplant recipients
      greater than 18 years old from 1995 to 2008 (n=26,804). Multivariable regression
      was performed in order to assess the simultaneous effect of multiple risk factors
      on posttransplant graft failure (PTGF) at 90 days. Secondary outcomes of interest
      included infection, stroke, and dialysis during the transplant hospitalization as
      well as primary nonfunction of the graft at 90 days. RESULTS: Among the study
      cohort, there were 90 (0.34%) re-Tx patients. Median survival in this group was
      1.6 years compared with 10.5 years for controls. Unadjusted PTGF, infection,
      dialysis, and primary nonfunction were significantly higher (p<0.001) in the re
      Tx group. After risk adjustment, however, PTGF (p=0.545), infection (p=0.696),
      dialysis (p=0.664), stroke (p=0.115), and primary nonfunction (p=0.531), did not
      differ significantly between the 2 groups. CONCLUSIONS: When controlling for
      pretransplant recipient characteristics, retransplantation within 90 days of a
      previous transplant is not associated with increased morbidity or mortality.
      However, unadjusted overall survival was significantly worse in the re-Tx group.
      This suggests that although retransplantation at 90 days alone is not a risk
      factor for inferior outcomes, given the significant comorbidities of these
      patients, the indications for retransplantation within 90 days are rare and must
      be critically examined.

PMID- 21871279
TI  - Late aortic insufficiency related to poor prognosis during left ventricular
      assist device support.
AB  - BACKGROUND: Management of native aortic insufficiency (AI) during left
      ventricular assist device (LVAD) support is challenging. We investigated the
      occurrence of de novo AI during long-term LVAD support to identify its effect on
      late clinical and echocardiographic outcomes. METHODS: Left ventricular assist
      devices were implanted in 99 patients with dilated cardiomyopathy, of whom 47
      without preoperative AI were investigated using serial echocardiography
      examinations for more than 1 year after the operation. RESULTS: The mean duration
      of LVAD support was 838+/-327 days, and 26 patients (55%) were supported for more
      than 2 years. Twenty-nine patients (62%) had no AI (group A), whereas de novo AI
      developed in the remaining 18 (38%; group B) at 1 year after LVAD implantation
      (>=grade 2 in 5, grade 1 in 13). The LV end-diastolic diameter was significantly
      reduced after LVAD implantation in both groups, with no significant difference
      between them. Overall survival was better in group A (p=0.0195). Multivariate
      analysis revealed that preoperative mitral regurgitation of more than grade 2
      (odds ratio, 7.8; 95% confidence interval, 1.2 to 48.6; p=0.028) and an aortic
      valve that remained closed at 1 month after implantation (odds ratio, 6.7; 95%
      confidence interval, 1.0 to 43.9; p=0.048) were significant independent
      predictors of de novo AI at 1 year after LVAD implantation. CONCLUSIONS: Survival
      was significantly worse when de novo AI developed in patients during long-term
      LVAD. Our findings indicate that preoperative functional mitral regurgitation and
      postoperative aortic valve opening are related to the progression of AI during
      long-term LVAD support.

PMID- 21871281
TI  - Comparative study of the Aristotle Comprehensive Complexity and the Risk
      Adjustment in Congenital Heart Surgery scores.
AB  - BACKGROUND: The Aristotle Comprehensive Complexity (ACC) and the Risk Adjustment
      in Congenital Heart Surgery (RACHS-1) scores have been proposed for complexity
      adjustment in the analysis of outcome after congenital heart surgery. Previous
      studies found RACHS-1 to be a better predictor of outcome than the Aristotle
      Basic Complexity score. We compared the ability to predict operative mortality
      and morbidity between ACC, the latest update of the Aristotle method and RACHS-1.
      Morbidity was assessed by length of intensive care unit stay. METHODS: We
      retrospectively enrolled patients undergoing congenital heart surgery. We modeled
      each score as a continuous variable, mortality as a binary variable, and length
      of stay as a censored variable. We compared performance between mortality and
      morbidity models using likelihood ratio tests for nested models and paired
      concordance statistics. RESULTS: Among all 1,384 patients enrolled, 30-day
      mortality rate was 3.5% and median length of intensive care unit stay was 3 days.
      Both scores strongly related to mortality, but ACC made better prediction than
      RACHS-1; c-indexes 0.87 (0.84, 0.91) vs 0.75 (0.65, 0.82). Both scores related to
      overall length of stay only during the first postoperative week, but ACC made
      better predictions than RACHS-1; U statistic=0.22, p<0.001. No significant
      difference was noted after adjusting RACHS-1 models on age, prematurity, and
      major extracardiac abnormalities. CONCLUSIONS: The ACC was a better predictor of
      operative mortality and length of intensive care unit stay than RACHS-1. In order
      to achieve similar performance, regression models including RACHS-1 need to be
      further adjusted on age, prematurity, and major extracardiac abnormalities.

PMID- 21871280
TI  - A novel method for quantifying the in-vivo mechanical effect of material injected
      into a myocardial infarction.
AB  - BACKGROUND: Infarcted regions of myocardium exhibit functional impairment ranging
      in severity from hypokinesis to dyskinesis. We sought to quantify the effects of
      injecting a calcium hydroxyapatite-based tissue filler on the passive material
      response of infarcted left ventricles. METHODS: Three-dimensional finite element
      models of the left ventricle were developed using three-dimensional
      echocardiography data from sheep with a treated and untreated anteroapical
      infarct, to estimate the material properties (stiffness) in the infarct and
      remote regions. This was accomplished by matching experimentally determined left
      ventricular volumes, and minimizing radial strain in the treated infarct, which
      is indicative of akinesia. The nonlinear stress-strain relationship for the
      diastolic myocardium was anisotropic with respect to the local muscle fiber
      direction, and an elastance model for active fiber stress was incorporated.
      RESULTS: It was found that the passive stiffness parameter, C, in the treated
      infarct region is increased by nearly 345 times the healthy remote value.
      Additionally, the average myofiber stress in the treated left ventricle was
      significantly reduced in both the remote and infarct regions. CONCLUSIONS:
      Overall, injection of tissue filler into the infarct was found to render it
      akinetic and reduce stress in the left ventricle, which could limit the adverse
      remodeling that leads to heart failure.

PMID- 21871282
TI  - Invited commentary.

PMID- 21871283
TI  - Efficacy and safety of aprotinin in neonatal congenital heart operations.
AB  - BACKGROUND: Aprotinin has been associated with significant morbidity and
      mortality in adults, leading to its withdrawal from the market and clinical
      substitution with the lysine analogs, tranexamic acid and epsilon-aminocaproic
      acid. Neonates undergoing cardiopulmonary bypass are especially at risk for
      perioperative bleeding, yet little data exist comparing lysine analogs with
      aprotinin. METHODS: Neonates undergoing cardiopulmonary bypass (January 2006 to
      December 2009) were included in this single-institution, retrospective cohort
      study. Preoperative, intraoperative, and postoperative data were analyzed. The
      relationship between demographic, surgical risk data, and outcomes were analyzed.
      Markers of effectiveness included transfusion requirement, duration of operation,
      duration of ventilation, and intensive care unit length of stay. Markers of
      safety included reexploration, renal dysfunction, neurologic complications, and
      death. RESULTS: Of 423 included neonates, 271 (64%) received aprotinin and 152
      (36%) a lysine analog. Infants who received aprotinin had a higher baseline
      creatinine and lower weight and gestational age. The aprotinin group experienced
      shorter time to surgical closure, lower blood product use, and lower rates of
      reexploration and postoperative renal dysfunction compared with the lysine-analog
      group. There was no difference in duration of ventilation or intensive care unit
      stay, neurologic outcomes, or death. CONCLUSIONS: Neonates who received aprotinin
      had significantly lower intraoperative transfusion requirements and shorter
      surgical closure times. The aprotinin group was less likely to require surgical
      reexploration and had a lower rate of renal injury. These data illustrate the
      need for further research regarding safety and efficacy of aprotinin in a larger
      sample of children undergoing cardiac operations.

PMID- 21871284
TI  - Perioperative use of dexmedetomidine is associated with decreased incidence of
      ventricular and supraventricular tachyarrhythmias after congenital cardiac
      operations.
AB  - BACKGROUND: Postoperative tachyarrhythmias remain a common complication after
      congenital cardiac operations. Dexmedetomidine (DEX), an alpha-2 adrenoreceptor
      agonist, can have a therapeutic role in supraventricular tachyarrhythmias for
      cardioversion to sinus rhythm or heart rate control. Whether routine
      perioperative use of DEX decreases the incidence of supraventricular and
      ventricular tachyarrhythmias was studied. METHODS: In this prospective cohort
      study, 32 pediatric patients undergoing cardiothoracic operations received DEX
      and were compared with 20 control patients who did not receive DEX. RESULTS:
      Dexmedetomidine was started after anesthesia induction and continued
      intraoperatively and postoperatively for 38+/-4 hours (mean dose, 0.76+/-0.04
      MUg/kg/h). Ten control patients and 2 DEX patients sustained 16 episodes of
      tachyarrhythmias (p=0.001), including a 25% vs 0% (p=0.01) incidence of
      ventricular tachycardia and 25% vs 6% (p=0.05) of supraventricular arrhythmias in
      the control and DEX group, respectively. Transient complete heart block occurred
      in 2 control patients and in 1 DEX patient. Control patients had a higher heart
      rate (141+/-5 vs 127+/-3 beats/min, p=0.03), more sinus tachycardia episodes (40%
      vs 6%; p=0.008), required more antihypertensive drugs with nitroprusside (20+/-7
      vs 4+/-1 MUg/kg; p=0.004) and nicardipine (13+/-5 vs 2+/-1 MUg/kg; p=0.02), and
      required more fentanyl (39+/-8 vs 19+/-3 MUg/kg; p=0.005). CONCLUSIONS:
      Perioperative use of dexmedetomidine is associated with a significantly decreased
      incidence of ventricular and supraventricular tachyarrhythmias, without
      significant adverse effects.

PMID- 21871285
TI  - Thirty-year experience with the arterial switch operation.
AB  - BACKGROUND: We evaluated the results of the arterial switch operation (ASO) being
      performed at our institution for more than 30 years and identified risk factors
      for mortality and reoperation. METHODS: Clinical outcome of 332 consecutive
      patients with transposition of the great arteries undergoing ASO was
      retrospectively analyzed, using surgical reports, medical charts, and latest
      follow-up echocardiography. Statistical analysis was performed using the Kaplan
      Meier method and univariable and multivariable binary logistic and Cox regression
      analyses. RESULTS: In-hospital mortality was 11.4%. At 15 years, estimated
      overall survival was 85.2%, and estimated freedom from reoperation was 74.0%.
      Cross-clamp time (p=0.001) and absence of the Lecompte maneuver (p=0.001) were
      identified as independent risk factors for in-hospital mortality, whereas
      coronary problems during surgery (p=0.009) and postoperative pacemaker
      implantation (p<0.001) were independent risk factors for late mortality.
      Independent risk factors for reoperation were higher age at the time of the ASO
      (p=0.002), presence of arch abnormalities (p<0.001), coronary problems during
      surgery (p=0.005), and duration of ventilation (p<0.001). At latest
      echocardiography, moderate or severe neoaortic regurgitation was present in 3.4%
      of the patients. CONCLUSIONS: Overall, 30 years of experience with the ASO shows
      good survival and event-free survival rates. Coronary transfer problems during
      surgery were found to be an important risk factor for late mortality and
      reoperation. However, coronary anatomy other than 1LCx-2R and an intramural
      course of the left coronary artery or left anterior descending artery were not
      risk factors for mortality or reoperation. Neoaortic regurgitation does not seem
      to form a major problem.

PMID- 21871286
TI  - Outcome of caval division techniques for partial anomalous pulmonary venous
      connections to the superior vena cava.
AB  - BACKGROUND: Correction of a high partial anomalous pulmonary venous (PV)
      connection to the superior vena cava (SVC) may be complicated by sinus node
      dysfunction, or SVC or PV obstruction. We have used the caval division technique
      when the anomalous PV insert high above the cavoatrial junction and report our
      long-term outcome. METHODS: Between 1990 and 2009, 178 consecutive patients
      underwent operations for a partial anomalous PV connection. Caval division was
      used in 41 patients (23%). Median age was 34 years (range, 1.3 to 76 years).
      Thirty patients (73%) had an atrial septal defect. Eighteen patients (44%)
      underwent Warden procedure in which the SVC was divided, the upper end was
      connected to the right atrial appendage, and the remaining SVC served as a
      conduit for PV drainage to the left atrium through the atrial septal defect. A
      modified Warden was performed in 17 patients (41%) using a short ringed
      interposition graft between the SVC and the right atrial appendage. Six patients
      (15%) with persistent left SVC underwent right SVC division without
      reimplantation. RESULTS: No early deaths occurred. One Warden group patient (5%)
      required early reoperation for SVC obstruction. One patient (2%) with atrial
      fibrillation underwent a concomitant Maze procedure and permanent pacemaker
      implantation for tachybrady syndrome. All other patients remained in sinus rhythm
      at follow-up. Follow-up was complete in all patients (mean, 2+/-2.6 years;
      maximum, 14 years). One noncardiac-related death occurred at 14 years. SVC
      obstruction developed in 3 Warden group patients (17%) and was managed with
      angioplasty and stenting. No patient had pulmonary vein stenosis on follow-up.
      CONCLUSIONS: Caval division techniques appear to be effective, with low morbidity
      and mortality. The modified Warden procedure may decrease the risk of SVC
      obstruction. Late arrhythmias or PV obstruction are uncommon.

PMID- 21871287
TI  - Intramural coronary length correlates with symptoms in patients with anomalous
      aortic origin of the coronary artery.
AB  - BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) from the
      opposite sinus of Valsalva is a rare congenital anomaly with the potential for
      myocardial ischemia and sudden death. This review evaluated our series of AAOCA
      patients, who underwent coronary artery unroofing, to test our hypothesis that
      the intramural length of the anomalous coronary artery correlates with symptoms.
      METHODS: A retrospective analysis of symptoms, preoperative imaging (computed
      tomography and magnetic resonance imaging), intraoperative assessment,
      perioperative course, and follow-up were reviewed. RESULTS: From 2005 to 2010, 27
      patients (70% male) underwent surgical AAOCA repair. Mean age was 14.3+/-12
      (range, 6 to 52) years. In 25 patients with right AAOCA, 14 had chest pain and 4
      had syncope. Both patients with left AAOCA had chest pain. AAOCA unroofing was
      done in 25 and side-to-side anastomosis in 2. The intramural coronary artery
      length measured intraoperatively correlated with preoperative symptoms
      (symptoms=10+/-3.58 mm, no symptoms=5.2+/-1.5 mm, p<.002), as did preoperative
      imaging measurements (symptoms=7.8+/-2.8 mm, no symptoms=5.3+/-0.8 mm, p<.001).
      Preoperative imaging strongly predicted the intraoperative measurement (r=0.81,
      p=0.00001). There were no deaths, significant morbidity, or recurrence of
      symptoms. CONCLUSIONS: Coronary unroofing for AAOCA is a safe method of enlarging
      the coronary orifice and eliminating the intramural course. Symptomatic patients
      had a longer intramural course than asymptomatic patients, as assessed by
      preoperative imaging and intraoperative measurements. These results may have
      important clinical implications in determining indications for operation.

PMID- 21871288
TI  - Outcomes of second-run extracorporeal life support in children: a single
      institution experience.
AB  - BACKGROUND: After weaning from mechanical circulatory support with extracorporeal
      membrane oxygenation or ventricular assist devices, patients may recurrently
      deteriorate and require reinstitution of support. Potential benefits of this
      desperate strategy are not well documented. METHODS: We reviewed the hospital
      records of all patients in whom second-run mechanical circulatory support was
      instituted from May 1988 to August 2010. RESULTS: Second-run support was
      instigated in 26 (4.6%) of 567 patients who underwent short-term mechanical
      circulatory support. Underlying pathologies requiring support were cardiac in 20
      patients (76.9%) and noncardiac in 6 patients (23.1%).The majority of patients
      were younger than 1 year old (73.1%, n=19). Fifteen patients (57.7%) survived
      second-run support, but only 7 patients (26.9%) survived to discharge from the
      hospital. After a median follow-up of 42.5 months (range, 16 to 66 months), 4
      patients (15.4%) were alive, but 3 of them had various degrees of developmental
      delay. CONCLUSIONS: Selection of patients who can benefit from second-run support
      is a complex process with unpredictable results. Survival after second-run
      mechanical circulatory support in children is worse compared with single-run
      patients. Long-term prospects for survivors are so grim that this strategy should
      probably not be recommended.

PMID- 21871289
TI  - Invited commentary.

PMID- 21871290
TI  - Enhanced in vivo function of bioartificial lungs in rats.
AB  - BACKGROUND: More than 11 million Americans live with chronic lung disease; in
      search for an alternative to donor organs, we attempted to regenerate lungs based
      on perfusion decellularized lung scaffolds that can be transplanted similar to a
      donor organ. METHODS: Cadaveric rat lungs were decellularized by detergent
      perfusion. Resulting scaffolds were mounted in bioreactors and seeded with
      endothelial and fetal lung cells. Biomimetic organ culture was maintained for 7
      days. Resulting bioartificial left lungs were transplanted in orthotopic position
      after left pneumonectomy in rats. Cadaveric left lung transplants and
      pneumonectomies served as controls. Blood gas analyses, compliance testing, and
      fluoroscopies were performed on postoperative days 1, 7, and 14. Lungs were
      removed for final analysis on day 14. RESULTS: Perfusion decellularization of
      cadaveric lungs yielded acellular scaffolds with intact architecture and matrix
      composition. Alveolar volumes, number, and size were comparable in bioartificial
      and native lungs, as were gas exchange, vital capacity and compliance in vitro.
      After using improved graft preservation and postoperative weaning protocols,
      animals could be fully recovered, and bioartificial lung constructs provided
      oxygenation as long as 7 days at levels comparable to cadaveric lung transplants.
      Compliance, gas exchange, and radiographic appearance gradually declined over the
      subsequent 7 days owing to progressive graft consolidation and inflammation.
      CONCLUSIONS: Perfusion decellularization of cadaveric lungs yields intact
      scaffolds that can be seeded with cells to generate bioartificial lung grafts.
      After orthotopic transplantation, grafts are perfused by the recipient's
      circulation, ventilated through the recipient's airway and provide gas exchange
      in vivo for 7 days.

PMID- 21871291
TI  - Invited commentary.

PMID- 21871293
TI  - Long-term follow-up after robotic thymectomy for nonthymomatous myasthenia
      gravis.
AB  - BACKGROUND: Thymectomy is recognized as a significant component in the treatment
      of myasthenia gravis. However, controversy exists as to the optimal surgical
      approach. This investigation summarizes our experience performing extended
      thymectomy using a robotic technique in a large group of patients with
      significant follow-up. METHODS: Data collection for patients undergoing robotic
      thymectomy for nonthymomatous myasthenia gravis over a 6-year period was
      prospectively performed. Patients were assessed using the Myasthenia Gravis
      Foundation of America's quantitative disease severity score and the post
      intervention status classification. RESULTS: During the study period, 75 patients
      underwent thymectomy by this method. Mean preoperative myasthenia gravis severity
      score was 2.7. Mean operative time was 113+/-46 minutes. Extubation in the
      operating room occurred in 73 (98%) patients. Mean intensive care stay and total
      hospital length of stay were 0.9 and 2.2 days respectively. Mean interval between
      surgery and return to work (or prethymectomy activities of daily living) was 15+/
      6 days. Significant improvement of myasthenia gravis symptoms occurred in 65
      (87%) patients with a mean follow-up of 45+/-14 months. CONCLUSIONS: Robotic
      assisted thymectomy is a safe and effective technique for patients with
      symptomatic myasthenia gravis. It allowed an extended thymectomy to be performed
      without the associated length of stay or recovery period of a transsternal
      approach while producing comparable rates of symptom improvement.

PMID- 21871292
TI  - Optimizing the minimally invasive approach to mediastinal parathyroid adenomas.
AB  - BACKGROUND: Patients with refractory hyperparathyroidism after neck exploration
      may have a mediastinal parathyroid gland that has not been identified reliably
      with a single radiologic study. We report 17 patients who underwent minimally
      invasive resection for mediastinal parathyroid adenomas after confirmatory
      multipoint radiologic imaging. METHODS: Fifteen patients underwent thoracoscopic
      procedures and 2 patients underwent mediastinoscopic procedures for resection of
      suspected mediastinal parathyroid adenoma. Preoperative localizing studies
      included sestamibi scan, computed tomography scan of the neck and chest, and
      selective venous sampling of parathyroid hormone levels. Once a mediastinal
      location was determined, thoracoscopic or mediastinoscopic resection was
      performed. Successful removal of parathyroid tissue was confirmed with a 50% or
      greater reduction in intraoperative parathyroid hormone levels. RESULTS:
      Parathyroid adenoma was resected in 88% of patients after the operation. The cure
      rate was 100% in patients with two or more concordant studies locating
      parathyroid tissue in the mediastinum and 60% in those with one positive study.
      The thoracostomy tube was removed on median postoperative day 1 (range, 0 to 2
      days). Median hospital stay was 3 days (range, 2 to 7 days). The most common
      complication was temporary hypocalcemia, which occurred in 18% of patients.
      CONCLUSIONS: Minimally invasive parathyroidectomy is an effective treatment of
      hyperparathyroidism caused by mediastinal parathyroid tissue. Targeted
      exploration depends on the guidance of preoperative localization studies and
      measurement of intraoperative parathyroid hormone levels to verify successful
      resection. Selective venous sampling and high-resolution computed tomography
      scanning can be helpful in patients with negative sestamibi scans.

PMID- 21871294
TI  - Long-term outcomes of en bloc resection of non-small cell lung cancer invading
      the thoracic inlet and spine.
AB  - BACKGROUND: The purpose of this study was to determine whether en bloc resection
      of non-small cell lung cancer (NSCLC) invading the thoracic inlet (TI) and spine
      can provide good long-term outcomes. METHODS: We studied 54 consecutive patients
      treated with en bloc resection of NSCLC invading the TI and spine between 1992
      and 2009 at our center. There were 36 men and 18 women with a mean age of 51
      years (range, 37 to 71 years). Tumor resection involved at least 2 vertebral
      levels. We divided the patients into 3 groups based on whether vertebral invasion
      involved the transverse process only, the intervertebral foramina, requiring
      hemivertebrectomies with spinal fixation, or the vertebral body, requiring total
      vertebral body resection with spinal fixation. RESULTS: Induction chemotherapy
      was given to 27 (50%) patients including 3 who also received induction
      radiotherapy. Nine (17%) patients were in the transverse process group, 42 (78%)
      in the intervertebral foramina group, and 3 (6%) in the vertebral body group.
      Resection involved the subclavian artery in 19 (35%) patients. Complete resection
      was achieved in 49 (91%) patients. There were no perioperative deaths or residual
      neurologic impairments. Recurrence occurred in 31 (57%) patients and was local
      (n=6), systemic (n=24), or both (n=1). Local recurrence was more common in
      patients with N2-3 disease (p=0.0008) and subclavian artery involvement
      (p=0.031). There was a nonsignificant increase in local recurrence in patients
      with positive resection margins (40% vs 10%, p=0.058). The 1-, 5-, and 10-year
      survival rates were 82%, 31%, and 31%, respectively. The 1-, 5- and 10-year
      disease-free survival rates were 63%, 28%, and 28%, respectively. Five patients
      are alive and free of disease 10 years after surgery. By multivariate analysis,
      factors that independently affected survival were incomplete (R1) resection
      (p=0.006; odds ratio 67; 95% confidence interval 1.5 to 11.3) and subclavian
      artery involvement (p=0.037; odds ratio 0.46; 95% confidence interval 0.2 to
      0.9). CONCLUSIONS: Good long-term survival can be achieved in highly selected
      patients with NSCLC invading the TI and spine, provided complete en bloc
      resection is performed.

PMID- 21871295
TI  - Characterization of novel synthesized small molecular compounds against non-small
      cell lung cancer.
AB  - BACKGROUND: With the exception of surgery, the standard platinum-based
      chemotherapeutic agents are the preferred treatment for non-small cell lung
      cancer (NSCLC); however little improvement (5-year survival) has been made.
      Therefore it is highly desirable to develop innovative therapeutic agents for
      NSCLC treatment. METHODS: Highly enantioselective synthetic methods were
      developed and a broad compound library was established. Cell toxicity, cell
      sensitivity, cell proliferation, cell invasion, and three-dimensional colony
      formation assays were used to assess the anticancer potential of these compounds
      in non-small-cell lung cancer (NSCLC) cell lines. RESULTS: We found that the S
      form of compound PL54 (PL54S, 5-20 MUM) exhibited strong anticancer activity in 5
      tested NSCLC cell lines. We further synthesized a highly pure R-form enantiomer
      of PL54 (PL54R) and its racemate (PL54Rac) and characterized their anticancer
      activities. The results showed that PL54S is more potent than PL54R and PL54Rac
      against the tested cell lines. Furthermore, less cellular toxicity was observed
      in the normal human lung fibroblasts. Similarly, PL54S displayed greater anti
      colony formation activity compared with PL54R and PL54Rac. The cellular
      sensitivity assay revealed that PL54S and PL54Rac significantly suppressed
      cologenic formation compared with PL54R and dimethyl sulfoxide controls (p<0.01).
      All PL54 compounds (5 to 20 MUM) significantly inhibited cell proliferation and
      invasion of the A549 cell line (p<0.01). A soft agar colony formation assay
      revealed that PL54S and PL54Rac (10 mM), but not PL54R, significantly inhibited
      colony formation of tested NSCLC cells (p<0.01). CONCLUSIONS: The stereospecific
      compounds may prove to be a novel technique for the treatment of NSCLC.

PMID- 21871296
TI  - Prognostic value of chromosomal imbalances in squamous cell carcinoma and
      adenocarcinoma of the lung.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most aggressive
      tumors, with a very low overall survival rate. We investigated surgically
      resected squamous cell carcinoma (SCC) and adenocarcinoma (AC) to identify
      chromosomal imbalances and their value for individual prognostication. METHODS: A
      total of 80 cases, including 55 SCC and 25 AC, were retrospectively analyzed by
      comparative genomic hybridization. To model the sequential cytogenetic events, an
      oncogenetic tree model was applied based on maximum likelihood estimation.
      Clinicopathologic data and follow-up data were correlated with chromosomal
      imbalances. RESULTS: Fifty-one percent of patients were in stage I, 32% in stage
      II, and 17% in stage III, without statistically significant differences in
      staging distribution between SCC and AC. The average number of copy number
      imbalances was higher in SCC than in AC (9.4+/-1.2 vs 5.4+/-1.1; p=0.11).
      Frequency of chromosomal imbalances at -3p, +3q, -4q, +5q, -5q, +7q, and -13q
      were significantly different between SCC and AC. Subsequently, oncogenetic tree
      modeling identified different clusters of chromosomal imbalances for SCC and AC.
      Appearance of the -3p-cluster in SCC was associated with decreased overall
      survival independent of clinicopathologic parameters (mean, 42.8+/-7.5 months vs
      80.1+/-9.1 months, log rank p=0.019), whereas in AC no prognostic value could be
      identified for specific clusters of chromosomal imbalances. CONCLUSIONS:
      Although, the limited number of analyzed cases allows a cautious statement on
      chromosomal imbalances, the oncogenetic tree modeling suggests distinct patterns
      of cytogenetic evolution for SCC and AC with implications for clinical outcome in
      SCC.

PMID- 21871298
TI  - Invited commentary.

PMID- 21871297
TI  - Activating enhancer-binding protein-2beta nucleolar localization predicts poor
      survival after stage I non-small cell lung cancer resection.
AB  - BACKGROUND: Activating enhancer-binding protein-2beta (AP2beta) is a
      transcription factor involved in apoptosis. The purpose of the current study was
      to assess the cellular location and level of AP2beta in non-small cell lung
      cancer (NSCLC) and normal lung tissue and investigate whether the level and
      localization of AP2beta expression is predictive of overall survival in patients
      with stage I NSCLC. METHODS: We performed immunohistochemical analysis of tissue
      microarrays (TMAs) prepared from stage I NSCLC specimens with adjacent normal
      lung tissue from two independent sets of patients who underwent lung resection
      with curative intent at our institution. The AP2beta intensity was assessed in
      TMAs, and AP2beta staining patterns were classified as either diffuse or
      nucleolar in the TMAs. The AP2beta intensity and localization were analyzed for
      correlation with patients' survival. RESULTS: Immunohistochemical analysis of
      TMAs showed that the intensity of AP2beta immunohistochemical staining did not
      correlate with overall survival. When location of AP2beta was analyzed in TMAs,
      all of the normal lung tissue had diffuse pattern of AP2beta. In the first set of
      NSCLC, patients with nucleolar pattern had a significantly lower 5-year survival
      rate than patients with diffuse pattern (67% versus 100%; p=0.004); this finding
      was confirmed in the second set (64% versus 91%; p=0.02). Multivariate analysis
      revealed that nucleolar pattern was an independent predictor of poor overall
      survival in both sets. CONCLUSIONS: The AP2beta, which is located in the
      nucleoplasm in normal lung tissue, is found in either nucleoplasm or nucleoli in
      NSCLC. The patients with AP2beta in the nucleoli had poor survival compared with
      patients with AP2beta in the cytoplasm.

PMID- 21871299
TI  - B-type natriuretic Peptide as a predictor of postoperative cardiopulmonary
      complications in elderly patients undergoing pulmonary resection for lung cancer.
AB  - BACKGROUND: The objective of the present study was to evaluate the utility of B
      type natriuretic peptide for prediction of postoperative cardiopulmonary
      complications in elderly patients undergoing pulmonary resection for lung cancer.
      METHODS: A prospective observational study was performed involving 80 consecutive
      patients aged 75 years or older who underwent a scheduled pulmonary resection for
      lung cancer in two specialized thoracic centers between January 2008 and June
      2010. Baseline clinical details were obtained, and spirometry and examination of
      serum B-type natriuretic peptide levels were performed before surgery. The
      primary endpoint was the incidence of postoperative cardiopulmonary
      complications. RESULTS: Postoperative cardiopulmonary complications were
      identified in 34 (43%) patients; these patients had significantly higher
      preoperative B-type natriuretic peptide levels than those without cardiopulmonary
      complications (84.0+/-93.7 pg/mL vs 22.0+/-18.2 pg/mL; p<0.0001). The area under
      the receiver operating characteristic curve for B-type natriuretic peptide to
      predict postoperative cardiopulmonary complications after pulmonary resection for
      lung cancer was 0.85 (95% confidence interval 0.76 to 0.94; p<0.0001). A B-type
      natriuretic peptide value of 30 pg/mL had a sensitivity of 79% and a specificity
      of 83% for predicting postoperative cardiopulmonary complications after pulmonary
      resection for lung cancer. The incidences of both cardiovascular and respiratory
      complications were significantly higher in patients with preoperative B-type
      natriuretic peptide levels of 30 pg/mL or more. CONCLUSIONS: Preoperative B-type
      natriuretic peptide level could be a useful predictor of postoperative
      cardiopulmonary complications in elderly patients after pulmonary resection for
      lung cancer.

PMID- 21871300
TI  - Previous head and neck cancers portend poor prognoses in lung cancer patients.
AB  - BACKGROUND: Although a common clinical pairing, the epidemiology and prognosis of
      lung cancer (LC) after head and neck cancer (HNC) is not well described. METHODS:
      Data from the database of the Surveillance, Epidemiology and End Results (SEER)
      Program were used to study the epidemiology and survival of patients with LC
      after HNC. These data were compared with those from our institutional cancer
      registry. RESULTS: Of all patients with a history of HNC in the SEER database,
      8,225 (5%) patients went on to develop LC. This was more than three times the
      incidence of second primary lung cancers (1.5%). Subsequent LCs in patients with
      a history of HNC were more common among those with hypopharyngeal and laryngeal
      cancer and those with localized HNC. Patients with HNC followed by LC had poorer
      overall survival than did the overall population of patients with LCs in the SEER
      database. Overall survival after the onset of LC was dismal (median survival, 8
      months). Survival was not affected by histologic concordance between HNC and LC.
      An analysis of 72 patients with LC after HNC reported in our institutional tumor
      registry over the past 37 years yielded similar results. CONCLUSIONS: Of patients
      who survive LC or HNC, the latter are much more likely to develop a new pulmonary
      malignancy. Lung cancers that develop after HNC have a poor prognosis. This
      phenomenon is not explained by misclassified metastases, because histologically
      discordant cases behave just as poorly. Enhanced surveillance and chemoprevention
      strategies are needed to detect and prevent subsequent primary LC in survivors of
      HNC.

PMID- 21871301
TI  - Characterization and prediction of prolonged air leak after pulmonary resection:
      a nationwide study setting up the index of prolonged air leak.
AB  - BACKGROUND: The objective of this study was to better characterize prolonged air
      leak (PAL), defined as an air leak longer than 7 days, and to develop and
      validate a predictive model of this complication after pulmonary resection.
      METHODS: All lung resections entered in Epithor, the French national thoracic
      database (French Society of Thoracic and Cardiovascular Surgery), were analyzed.
      Data collected between 2004 and 2008 (n=24,113) were used to build the model
      using backward stepwise variable selection, and the 2009 data (n=6,813) were used
      for external validation. The primary outcome was PAL. Results of the predictive
      model were used to propose a score: the index of PAL (IPAL). RESULTS: Prevalence
      of PAL after pulmonary resection was 6.9% (n=1,655) in the development data set.
      In the final model, 9 variables were selected: gender, body mass index, dyspnea
      score, presence of pleural adhesions, lobectomy or segmentectomy, bilobectomy,
      bulla resection, pulmonary volume reduction, and location on upper lobe. In the
      development data set, the C-index was 0.71 (95% confidence interval [CI], 0.70 to
      0.72). At external validation, the C-index was 0.69 (95% CI, 0.66 to 0.72) and
      the calibration slope (ie, the agreement between observed outcomes and
      predictions) was 0.874 (<1). A score chart based on these analyses has been
      proposed. The formula to calculate the IPAL is the following: gender (F=0; M=4)
      (body mass index-24)+2*dyspnea score+pleural adhesion (no=0; yes=4)+pulmonary
      resection (wedge=0; lobectomy or segmentectomy=7; bilobectomy=11; bulla
      resection=2; volume reduction=14)+location (lower or middle lobe=0; upper=4).
      CONCLUSIONS: Surgeons can easily use the well-validated model to determine
      intraoperative preventive measures of PAL.

PMID- 21871302
TI  - Impact of hospital volume on chest tube duration, length of stay, and mortality
      after lobectomy.
AB  - BACKGROUND: Numerous studies have suggested an inverse relationship between
      hospital volume and short-term mortality after various major operations. However,
      the volume-outcome relationship after lung cancer surgery remains controversial.
      We investigated the effects of hospital volume on various outcomes after
      lobectomy for lung cancer, including chest tube duration, postoperative length of
      stay, and in-hospital mortality. METHODS: From a total of 5.85 million inpatients
      in the Japanese Diagnosis Procedure Combination database, we identified 19,831
      patients who underwent lobectomy for lung cancer between July and December in
      2007 and 2008. Patients were divided into low (<=24 per year), medium-low (25 to
      43), medium-high (44 to 67), or high (>=68) hospital-volume groups. Multivariate
      regression analyses were conducted to analyze the concurrent effects of various
      factors on postoperative outcomes. RESULTS: Overall in-hospital mortality was
      0.69%, and was significantly lower in the high-volume group compared with the low
      volume group (0.48% versus 0.94%; odds ratio 0.60; p=0.047). Chest tube removal
      occurred earlier in the high-volume group than in the low-volume group (mean 4.0
      days versus 5.1; p<0.001). Postoperative length of stay was shorter in the high
      volume group than in the low-volume group (mean 11.5 days versus 15.9, p<0.001).
      CONCLUSIONS: Higher hospital volume was associated with significantly shorter
      chest tube duration and postoperative length of stay, and lower in-hospital
      mortality after lobectomy for lung cancer. However, the differences in outcomes
      between high-volume and low-volume hospitals may be too small to support
      regionalization of lung cancer operations to high-volume centers.

PMID- 21871303
TI  - Invited commentary.

PMID- 21871304
TI  - Benign emptying of the postpneumonectomy space.
AB  - BACKGROUND: A fall in the postpneumonectomy fluid level is considered a sign of
      bronchopleural fistula (BPF) requiring surgical intervention. We have discovered
      however that in rare asymptomatic patients, this event may not require aggressive
      surgical treatment. METHODS: After seeing a case of benign emptying of the
      postpneumonectomy space (BEPS), we surveyed 28 surgeons to determine its
      incidence and characteristics. RESULTS: Forty-four cases of BEPS were reported by
      23 survey respondents. Among 7 fully documented cases from 4 institutions, we
      defined the following criteria: the patient must be asymptomatic (no fever, white
      cell count elevation, or fluid expectoration), negative culture results if fluid
      sampled (patient not receiving antibiotics), no BPF at bronchoscopy or
      ventilation scintigraphy scan (or both), and recovery without drainage, or
      retrospective assessment that the intervention was unnecessary. BEPS occurred
      between 5 days and 152 days after pneumonectomy (6 cases right pneumonectomy and
      1 case left pneumonectomy). Four patients underwent no treatment, 1 patient
      underwent thoracoscopic exploration (sterile) and closure after antibiotic
      irrigation, 1 patient underwent thoracoscopic exploration alone, and 1 patient
      underwent open window thoracostomy (sterile) with eventual closure. In all 7
      patients (except the patient who underwent the open window procedure) the space
      refilled within 8 weeks; no patient experienced a subsequent empyema/BPF. Four
      patients who met the initial criteria for BEPS went on to experience empyema. The
      incidence of BEPS appears related to pneumonectomy volume, particularly
      extrapleural pneumonectomy. Using surgeon volume assumptions, the incidence of
      BEPS is 0.65%. CONCLUSIONS: To our knowledge, BEPS is a previously unreported
      occurrence. We hypothesize that it results from postoperative intrapleural
      pressure shifts, with or without a microscopic BPF, that drive fluid out of the
      pleural space while failing to cause contamination. Awareness of BEPS' existence
      may allow surgeons to safely avoid open drainage procedures occasionally in
      patients who experience an asymptomatic fall in fluid level.

PMID- 21871305
TI  - Invited commentary.

PMID- 21871306
TI  - Ultrasonographic identification of peripheral pulmonary nodules through uniportal
      video-assisted thoracic surgery.
AB  - PURPOSE: An intrinsic limitation of video-assisted thoracic surgery (VATS)
      resides in the impossibility to palpate the lung to identify embedded nodules. We
      wanted to investigate the use of intraoperative ultrasonography to detect
      pulmonary nodules during uniportal VATS. DESCRIPTION: We describe our initial
      experience with the identification of peripheral pulmonary nodules with an
      articulating ultrasound probe introduced through a single VATS incision. The
      instrument was used in 2 patients with solitary pulmonary nodules and previous
      history of extrathoracic cancer. EVALUATION: The lung nodules were identified by
      the articulating probe and resected on wide tumor-free margins through uniportal
      VATS. Subsequent lung palpation through minithoracotomy confirmed the absence of
      additional lesions. CONCLUSIONS: Intraoperative ultrasound scanning of the lung
      with an articulating probe can be successfully used through uniportal VATS to
      identify peripheral nodules.

PMID- 21871307
TI  - Management of aortic valve dysfunction after transapical approach using the
      technique "valve after valve".
AB  - We report a case of a 77-year-old patient with severe aortic stenosis who
      underwent transapical aortic valve implantation with a 23-mm Edwards Sapien valve
      (Edwards Lifesciences Inc, Irvine CA). This procedure was complicated with the
      occurrence of an acute regurgitation due to entrapment of one of the leaflets
      that was successfully managed by valve after valve technique.

PMID- 21871308
TI  - Double-valve replacement for Scheie's syndrome subtype mucopolysaccaridosis type
      1-S.
AB  - Scheie's syndrome is a rare hereditary disorder of proteoglycan-degrading
      enzymes. Deposition of mucopolysaccharide can cause valvular and other tissue
      abnormalities. Few studies have reported surgical results for Scheie's syndrome,
      and the perioperative course is complicated. This is a report of a 35-year-old
      woman with Scheie's syndrome who underwent double-valve replacement with
      intensive perioperative management.

PMID- 21871309
TI  - Open plugging and extra-anatomical bypass for iatrogenic rupture of coarctation
      of the aorta.
AB  - We report a successful repair of aortic rupture after balloon angioplasty for re
      coarctation using a unique approach and method. A 22-year-old woman underwent
      emergency surgery for aortic rupture after balloon angioplasty for postoperative
      aortic re-coarctation. We performed extra-anatomic bypass from the ascending
      aorta to the descending thoracic aorta through a median sternotomy and incision
      in the posterior pericardium. The transverse aortic arch was transected, and the
      distal aortic arch was opened under deep hypothermic circulatory arrest of the
      lower extremities. The proximal aorta was closed. To seal the aortic rupture
      site, a tube graft was inserted through the aortotomy and was oversewn with the
      aorta. Repair of the right ventricular outflow stenosis was concomitantly
      performed. The patient's postoperative course was uneventful, and she
      successfully gave birth 2 years postoperatively.

PMID- 21871310
TI  - Alternative surgical approach to repair of the ascending aorta.
AB  - We describe a case of complete endovascular repair of the ascending aorta using a
      transfemoral approach. A 59-year-old man with a history of two previous
      sternotomies experienced an ascending aortic pseudoaneurysm arising from the
      graft-to-graft anastomosis of a previous DeBakey type I aortic dissection repair.
      A custom-made Zenith TX2 (William Cook Europe ApS, Bjaeverskov, Denmark) thoracic
      aortic aneurysm endovascular graft, designed specifically for the ascending
      aorta, was introduced through the left femoral artery and deployed under a rapid
      ventricular pacing protocol to achieve precise placement between the sinotubular
      junction and the aortic arch.

PMID- 21871311
TI  - Single-stage repair of interrupted aortic arch with simultaneous coronary artery
      bypass grafting without cardiopulmonary bypass in an adult.
AB  - Interrupted aortic arch is a rare congenital cardiac defect. There are extremely
      few cases in adults that are reported in the pertinent medical literature.
      However, single-stage repair of interrupted aortic arch combined with coronary
      artery disease has been rarely reported. We describe the management of
      interrupted aortic arch associated with coronary artery disease through single
      stage surgical procedure without cardiopulmonary bypass in a 56-year-old woman.
      The vascular prosthesis was anastomosed between the aortic arch just distal to
      the origin of the left subclavian artery and the descending thoracic aorta. Then
      a venous bypass was subsequently formed between the left anterior descending
      coronary artery, the circumflex artery, and the descending aorta.

PMID- 21871312
TI  - A rare case of an extracardiac unruptured aneurysm of the sinus of valsalva in a
      patient with single coronary artery.
AB  - A 75-year-old man with gastric cancer underwent preoperative cardiac examination
      by echocardiography, and an unruptured extracardiac aneurysm was detected in the
      right sinus of Valsalva. Coronary angiography by multidetector computed
      tomography demonstrated a single left coronary artery. Patch closure of the
      orifice of the aneurysm of the right sinus of Valsalva was successfully performed
      for this extremely rare combination.

PMID- 21871313
TI  - Hypoplastic left heart syndrome with valvular pulmonary stenosis: successful
      management with norwood staged reconstruction.
AB  - The association of hypoplastic left heart syndrome with valvular pulmonary
      stenosis is rare and is not well-described in the literature. Here we describe
      the experience of Norwood stage one reconstruction in an infant with hypoplastic
      left heart syndrome and significant pulmonary stenosis. The baby was successful
      palliated and stage II reconstruction with a bidirectional Glenn shunt was also
      later performed. Even though this condition is considered a poor candidate for
      Norwood stage one reconstruction because of outflow obstruction, Norwood stage
      one reconstruction was used because neonatal transplantation is not a feasible
      option in Taiwan. This experience suggested that Norwood staged reconstruction is
      an option for this difficult condition.

PMID- 21871314
TI  - An unusual complication from hemostatic packing to control bleeding during
      cervical mediastinoscopy and an off-pump approach for the later exploration of
      the superior vena caval injury.
AB  - Cervical mediastinoscopy has been widely used and is considered a safe method for
      the histologic diagnosis and staging of many conditions. Hemorrhage still remains
      one of the main possible complications, and hemostasis is usually achieved
      without any further surgical intervention. We present a previously unreported
      complication of absorbable hemostatic gauze packing, which led to superior vena
      caval injury and multiple pulmonary emboli, necessitating further surgical repair
      with the use of a veno-venous shunt.

PMID- 21871315
TI  - A thyroglossal duct cyst of the anterior mediastinum.
AB  - Thyroglossal duct cysts (TGDCs) are developmental anomalies arising from the
      embryonic thyroglossal duct. They are commonly midline cervical structures
      associated with the hyoid bone. We report a 3.5-cm diameter isolated TGDC of the
      anterior mediastinum in a 65-year-old European woman who was treated by
      transcervical excision. The mass was limited to the mediastinum with a normal
      neck on computed tomographic scan and clinical examination. This is the second
      case of mediastinal TGDC known to be reported, and the oldest known age at
      presentation. The TGDC should be considered as an uncommon differential diagnosis
      of an anterior mediastinal mass.

PMID- 21871316
TI  - Role of surgery after chemotherapy in B-cell lymphoma of thymus causing airway
      compression and right ventricle outflow tract obstruction.
AB  - Primary B-cell lymphoma of thymus is uncommon. We describe the case of a 23-year
      old woman with a history of shortness of breath and distended neck veins of 1
      month duration. A chest roentgenogram and computed tomographic chest scan of the
      showed a large anterior mediastinal mass. Tru-cut biopsy revealed primary B-cell
      lymphoma of thymus. She underwent chemotherapy with no symptomatic improvement.
      Post-chemotherapy computed tomographic scan of the chest showed no appreciable
      reduction in tumor size. Surgical excision was carried out with excellent
      results.

PMID- 21871317
TI  - Life-threatening complications related to minocycline pleurodesis.
AB  - For decades, chemical pleurodesis using minocycline has been widely accepted as
      an effective, safe, and cheap treatment for persistent air leak after pulmonary
      resection. We report a case with persistent postoperative air leak that suffered
      from cardiorespiratory arrest just after a minocycline pleurodesis, which may be
      related to the aspiration of minocycline solution from a bronchopleural fistula.
      Therefore, we suggest a bronchoscopic examination be performed before the
      pleurodesis if a bronchopleural fistula is highly suspected.

PMID- 21871318
TI  - Occurrence of a simultaneous bilateral spontaneous pneumothorax due to a pleuro
      pleural communication.
AB  - Herein we present a case of a simultaneous bilateral spontaneous pneumothorax
      caused by a pleuro-pleural communication. A 70-year-old man with a history of
      esophagectomy presented with dyspnea. A chest roentgenogram revealed a bilateral
      pneumothorax and bilateral chest drainage procedures were performed. A left
      bullectomy was also performed 3 days later due to persistent air leakage on the
      left side. During surgery, a small fistula was detected in the anterior
      mediastinal pleura and was found to be in communication with the bilateral
      pleural spaces.

PMID- 21871319
TI  - Tracheal stenosis due to relapsing polychondritis managed for 16 years with a
      silicon T-tube covering the entire trachea.
AB  - We report the case of a 35-year-old man with tracheal stenosis caused by
      relapsing polychondritis. The disease began at age 17, and he underwent steroid
      therapy and tracheostomy. After 2 years, owing to inflammation and fibrosis, a T
      tube was inserted from the glottis to the tracheal bifurcation. Besides
      hospitalization for mild pneumonia, the patient was able to lead a normal
      sedentary life with satisfactory communication. T-tubes are an effective and low
      risk treatment measure for preserving airway function in patients with tracheal
      stenosis due to polychondritis. In this report we discuss the advantages and
      disadvantages of different stents in treating relapsing polychondritis.

PMID- 21871321
TI  - Massive thymolipoma in a young asymptomatic male.

PMID- 21871320
TI  - Cardiac synovial sarcoma swinging through the aortic valve.

PMID- 21871322
TI  - Extension of metastatic lung cancer from cervix cancer through pulmonary vein
      into the left atrium.

PMID- 21871323
TI  - Measured tube technique for ensuring the correct length of slippery artificial
      chordae in mitral valvuloplasty.
AB  - Mitral valvuloplasty using Gore-Tex (W.L. Gore & Associates, Inc, Flagstaff, AZ)
      as artificial chordae is often associated with difficulties in determining the
      length of the artificial chordae, as well as preventing knot slippage, especially
      for patients with broad anterior leaflet prolapse. We describe a simple technique
      that enables surgeons to easily determine the correct length of the artificial
      chordae and tie slippery knots without using a specific device.

PMID- 21871324
TI  - Left pulmonary artery coarctoplasty by using the right pulmonary artery flap near
      the arterial duct.
AB  - Coarctation of the left pulmonary artery may coexist with tetralogy of Fallot or
      pulmonary atresia with ventricular septal defect. Various surgical methods, such
      as autologous pericardial patching and intraoperative pulmonary artery stenting,
      have been used for solving this condition. We proposed a simple and effective
      technique for treating patients with left pulmonary artery coarctation and
      pulmonary atresia with ventricular septal defect by using the right pulmonary
      artery flap for left pulmonary artery coarctoplasty, plus central shunt creation
      by V-Y plasty.

PMID- 21871325
TI  - Three-region perfusion strategy for aortic arch reconstruction in the Norwood.
AB  - We describe a new method of selective regional perfusion during arch
      reconstruction in the Norwood procedure. The strategy involves direct sequential
      perfusion of the coronary and splanchnic circulations coupled with continuous
      cerebral perfusion, while repairing the arch in a distal to proximal fashion.
      This technique provides the potential for decreased coronary and splanchnic
      ischemic times, which in combination with continuous selective cerebral perfusion
      may further allow for warmer operating temperatures and decreased overall bypass
      times.

PMID- 21871326
TI  - Morcellation technique to remove large tumor in thoracoscopic surgery.
AB  - Extraction of tumors remains a major problem in thoracoscopic surgery. In this
      study, we used an efficient instrument to morcellate a tumor during thoracoscopic
      surgery. The cosmetic result of this technique was satisfactory; thus, we suggest
      that this technique is a reliable option for use during thoracoscopic surgery for
      benign solid tumors.

PMID- 21871327
TI  - The Society of Thoracic Surgeons practice guideline on the prophylaxis and
      management of atrial fibrillation associated with general thoracic surgery:
      executive summary.

PMID- 21871329
TI  - The obesity paradox and cardiac surgery: are we sending the wrong message?

PMID- 21871330
TI  - The obesity paradox in coronary patients: myth or reality?

PMID- 21871331
TI  - Outcomes of minimally invasive valve surgery compared to conventional valve
      surgery in the elderly.

PMID- 21871334
TI  - No Ross operation for patients with aortic regurgitation?

PMID- 21871335
TI  - Appropriate assessment of operative risk in patients with severe symptomatic
      aortic stenosis: importance for patient selection in the era of transcatheter
      aortic valve implantation.

PMID- 21871337
TI  - Why are ITA free flows measured this low?

PMID- 21871339
TI  - Successful management of cervical esophageal perforation after anterior cervical
      surgery.

PMID- 21871341
TI  - [An exciting period, "the best is always to come"].

PMID- 21871342
TI  - The omega on alpha and beta.

PMID- 21871344
TI  - Difficulties to detect in-transit lymphatic metastasis in patients with
      rhabdomyosarcoma of the extremity: in regard to La et al. (Int J Radiat Oncol
      Biol Phys 2011; 80: 1151-1157.).

PMID- 21871346
TI  - All-arthroscopic repair of peripheral triangular fibrocartilage complex tears
      using FasT-Fix.
AB  - Injury to the triangular fibrocartilage complex (TFCC) is a major source of ulnar
      sided wrist pain that results in disability with common activities of daily
      living involving forearm rotation, for which operative management is indicated if
      conservative management fails. Past results with open repairs have been
      successful, but recent surgical advances have allowed the development of
      arthroscopic management. This article describes and reviews an all-arthroscopic
      technique of repair of Palmer type IB TFCC injuries with FasT-Fix suture
      technology (Smith and Nephew, Andover, MA, USA), which is advantageous both
      biomechanically and in terms of decreasing risk of morbidity.

PMID- 21871347
TI  - Radial side (1D) tears.
AB  - The triangular fibrocartilage complex (TFCC) is the key structure at the wrist
      that facilitates the rotation of the radius and the carpus on the distal ulnar.
      The radial or type 1D tears of the TFCC are uncommon, but they pose a major
      disruption of the articular contact between the carpus and the distal ulna. The
      tears can heal by arthroscopically repairing the TFCC back to the radius using
      sutures through bone tunnels. This procedure allows patients to return to their
      work and sports activities with significant recovery of strength and range of
      motion.

PMID- 21871348
TI  - Arthroscopic evaluation of the foveal attachment of the triangular
      fibrocartilage.
AB  - Anatomical and biomechanical studies have highlighted the importance of the deep
      attachment of the TFCC for maintaining stability of the distal radioulnar joint
      (DRUJ). The standard arthroscopic assessment of the TFCC does not allow one to
      definitively determine whether the deep fibers are indeed intact, and
      establishing the diagnosis of a foveal detachment remains an exacting challenge.
      DRUJ arthroscopy is useful to assess the foveal fibers in any patient with DRUJ
      instability and can aid in the surgical decision making.

PMID- 21871349
TI  - Foveal TFCC tear classification and treatment.
AB  - During the last two decades, increased knowledge of functional anatomy and
      pathophysiology of the triangular fibrocartilage complex (TFCC) have contributed
      to a change in surgeons' perspective toward it. The earlier concept of the TFCC
      as the "hammock" structure of the ulnar carpus has updated to the "iceberg"
      concept, whereby the much larger "submerged" part represents the foveal
      insertions of the TFCC and functions as the stabilizer of the distal radioulnar
      joint and the ulnar carpus, thus lending it greater functional importance. This
      article presents an algorithm of the treatment of traumatic peripheral TFCC tear
      based on clinical, radiological, and arthroscopic findings.

PMID- 21871350
TI  - Arthroscopic knotless peripheral ulnar-sided TFCC repair.
AB  - Peripheral ulnar-sided tears of the triangular fibrocartilage complex (TFCC) are
      common injuries and are amenable to arthroscopic repair. This article describes
      an all-arthroscopic knotless technique for TFCC repair. This technique has the
      advantage of being all arthroscopic using 3 portals, has the ability to repair
      both the superficial and deep layers of the articular disk, repairs the articular
      disk directly back to bone, and does not require any suture knots that may
      irritate the surrounding soft tissues. The surgical technique is described in
      detail.

PMID- 21871351
TI  - Repair of foveal detachment of the triangular fibrocartilage complex: open and
      arthroscopic transosseous techniques.
AB  - Because the radioulnar ligament attaches to the ulnar fovea and base of the ulnar
      styloid, foveal detachment of the triangular fibrocartilage complex (TFCC)
      induces severe distal radioulnar joint instability. This article describes both
      an arthroscopic and open repair technique to reattach the TFCC to the fovea. Both
      techniques reanchor the detached TFCC to the fovea. Both techniques are reliable
      and promising techniques in the repair of a foveal detachment of the TFCC.

PMID- 21871352
TI  - Minimal invasive management of scaphoid fractures: from fresh to nonunion.
AB  - The peculiar shape of scaphoid hinders a precise evaluation of its fracture
      configuration, displacement and accuracy of screw placement. Its tenuous vascular
      supply risks the complications of delayed union, nonunion and avascular necrosis.
      Scaphoid is the focus of ligamentous attachment governing carpal kinematics.
      Preservation of its anatomy and vascularity is critical for normal wrist
      function. A new fracture classification clearly denoting every fracture type and
      guiding the management is introduced. The minimal invasive management of
      different scaphoid fracture conditions, including acute non-displaced and
      displaced fracture, delayed presentation, and nonunion are discussed. Role of
      arthroscopy is emphasized. Detailed surgical techniques are shared here.

PMID- 21871353
TI  - The use of thermal shrinkage for scapholunate instability.
AB  - Scapholunate interosseous ligament (SLIL) instability is the most common form of
      carpal instability. There is a lack of consensus among hand surgeons as to the
      appropriate treatment of various stages. This article reviews the background and
      results of thermal treatment of predynamic instability of the SLIL. Case examples
      are discussed as well as a series of patients treated with our protocol for this
      injury.

PMID- 21871354
TI  - Arthroscopic treatment of scaphotrapeziotrapezoid osteoarthritis.
AB  - Scaphotrapeziotrapezoid (STT) joint osteoarthritis accounts for 13% of all wrist
      arthritis cases. The arthroscopic treatment combines radial midcarpal portal and
      STT portal called 1-2 midcarpal portal. We performed 13 isolated resections from
      the scaphoid distal pole. Patients were only women (average age, 58 years). Pain,
      mobility, and muscular strength improved significantly. At the same time, we
      fitted an interposition pyrocarbon implant after resection in 13 patients
      (average age, 67 years). We had 2 implant dislocations due to technical errors.
      Outcome quality optimized by the initial mini-invasive approach and arthroscopy
      should make selection of some treatment indications possible.

PMID- 21871355
TI  - Arthroscopic assessment of avascular necrosis.
AB  - Avascular necrosis of the lunate is a process that is not well understood. The
      cause is uncertain, but a common theory persists that it is caused by disruption
      of the vascular supply to the lunate. This article discusses an approach to
      assessment that respects the articular cartilage and places at the front of the
      decision-making process the pathoanatomic components of the articular cartilage.
      It primarily respects the articular cartilage in the patient with avascular
      necrosis. This approach was developed for avascular necrosis of the lunate, but
      in principle applies to other joints with avascular necrosis as well.

PMID- 21871356
TI  - Arthroscopic management of septic arthritis of the wrist.
AB  - Bacterial septic arthritis of the wrist is a joint-threatening emergency that is
      often treated by open irrigation and debridement (I and D). There is evidence
      that patients with isolated septic arthritis of the wrist require fewer
      operations and have a shorter hospital stay when treated arthroscopically. This
      article describes the surgical technique for arthroscopic I and D of the wrist
      and discusses the indications and benefits of arthroscopic versus open I and D
      for septic arthritis of the wrist.

PMID- 21871357
TI  - Dry arthroscopy and its applications.
AB  - Wrist arthroscopy can be performed without infusing fluid, as simple traction
      suffices to maintain the working space. The lack of tissue infiltration by fluid
      keeps soft tissues in pristine condition if open surgery is needed after the
      arthroscopic exploration. The dry technique makes fluid distension irrelevant,
      thus opening new possibilities by combining arthroscopy with moderate-sized
      incisions. Although any modification of a technique with which one is familiar
      can be regarded with major reticence, the advantages of the dry technique merit
      its use. Accomplished wrist arthroscopists will have minimal problems swapping
      from the wet to the dry and vice versa.

PMID- 21871358
TI  - Arthroscopic hemiresection for stage II-III trapeziometacarpal osteoarthritis.
AB  - Trapeziometacarpal osteoarthritis is a common problem, due to the anatomy of the
      first ray and the forces applied to the trapeziometacarpal joint throughout
      activities of daily living. Numerous treatment options exist, and continue to be
      developed, for this problem. The current goal is to eliminate pain and restore
      function and strength in a timely manner. New advances allow for earlier return
      to function with minimally invasive techniques. Arthroscopic hemitrapeziectomy
      combined with interposition arthroplasty and/or suspensionplasty is a treatment
      option for Stage II and III trapeziometacarpal arthritis that uses a minimally
      invasive technique and allows for earlier return of function.

PMID- 21871359
TI  - Bone-preserving arthroscopic options for treatment of thumb basilar joint
      arthritis.
AB  - While trapeziectomy with or without interposition arthroplasty and ligament
      reconstruction or suspensionplasty have been demonstrated to have a high rate of
      satisfactory outcomes, recent interest has focused on arthroscopy because of its
      perceived limited invasive nature as well as its versatility. In addition, using
      the arthroscope, other options are available that preserve all or part of the
      trapezium to limit subsidence of the thumb axis, preserve grip and pinch
      strength, and retain later options for joint reconstruction, should that become
      necessary.

PMID- 21871360
TI  - Arthroscopic reduction and percutaneous fixation of fifth carpometacarpal
      fracture dislocations.
AB  - Arthroscopy of the first carpometacarpal (CMC) joint has become routine. Similar
      techniques can be applied to fracture dislocations involving the fifth CMC joint.
      This situation is one whereby arthroscopy is definitely of benefit, because the
      articular fracture fragment is often volar, and difficult to visualize and reduce
      from a dorsal approach. This article describes arthroscopic techniques for
      reduction and percutaneous fixation of fifth CMC fracture dislocations.

PMID- 21871361
TI  - Metacarpophalangeal joint arthroscopy: indications revisited.
AB  - Arthroscopic surgery has become the gold standard for the diagnosis and treatment
      of major joint disorders. With advancement in arthroscopic technique, arthroscopy
      has become feasible in most human joints, even those as small as the finger
      joints. The metacarpophalangeal joint (MCPJ) can become spacious with simple
      traction, the intra-articular anatomy is simple, and its major structures can be
      easily visualized and identified. However, MCPJ arthroscopy has never been
      popular. This article describes our experience with MCPJ arthroscopy and seeks to
      establish its role in clinical practice.

PMID- 21871362
TI  - New frontiers in hand arthroscopy.
AB  - This article covers new and emerging techniques in small joint arthroscopy in the
      hand. Recent improvement in the quality of small joint scopes and advancement in
      techniques have allowed for many new small joint arthroscopic procedures in the
      hand. The arthroscopic classification for thumb carpometacarpal (CMC) arthritis
      as well as treatment of each stage are described. Arthroscopic treatment of
      pantrapezial arthrosis is reviewed. Metacarpophalangeal arthroscopy for the
      treatment of synovitis, arthritis, fractures, and gamekeeper injuries are
      discussed, as is arthroscopy of the proximal interphalangeal, pisotriquetral,
      fourth and fifth CMC, and distal interphalangeal joints.

PMID- 21871363
TI  - Arthroscopic synovectomy of the wrist.
AB  - Arthroscopic synovectomy is safe and reliable, with mild postoperative morbidity.
      The rationale of a surgical synovectomy is to excise inflamed synovium and
      thereby, remove as much effusion and inflammatory substrate as possible. In most
      cases, arthroscopic synovectomy is performed as an outpatient procedure. The
      technique has also been used for other diagnoses causing wrist arthritis, but
      very few results have been reported and the indications remain to be defined. In
      rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus
      erythematosus (SLE), and postinfectious monoarthritis, a long period of increased
      comfort and improved function can be anticipated.

PMID- 21871364
TI  - In this issue/abstract thinking: here, there, everywhere!

PMID- 21871365
TI  - Thank goodness for Uncle Sam and the National Institute of Mental Health
      Intramural Program.

PMID- 21871366
TI  - Pharmacotherapy of anorexia nervosa: more questions than answers.

PMID- 21871367
TI  - Links between autism spectrum disorder and ADHD symptom trajectories: important
      findings and unanswered questions.

PMID- 21871368
TI  - Nonsuicidal self-injury in an American Indian reservation community: results from
      the White Mountain Apache surveillance system, 2007-2008.
AB  - OBJECTIVE: To describe characteristics and correlates of nonsuicidal self-injury
      (NSSI) among the White Mountain Apache Tribe. NSSI has not been studied before in
      American Indian samples despite associated risks for suicide, which
      disproportionately affect American Indian youth. METHOD: Apache case managers
      collected data through a tribally mandated surveillance system. Data from 2007
      and 2008 (N = 182) were examined for rates, methods, precipitants, functions,
      past history of self-injury and service use, by age and gender. RESULTS: The rate
      of NSSI among all ages was 600 in 100,000, with individuals 10 to 14 years old
      disproportionately affected at a rate of 3,000 in 100,000. More females (65%)
      reported NSSI, and cutting was the preferred method (98%) for both genders
      combined. Most frequently reported precipitants were peer pressure/copying,
      conflict with boy/girlfriend and "depression." A substantial proportion (22%) was
      intoxicated/high at the time. More reported the function of NSSI was to "effect
      internal state" (45%) than "effect circumstances" (15%). More than one-third
      (39%) received ED treatment and referrals for aftercare (36%). Of those referred,
      only 30% followed up with services. Most (79%) reported past NSSI; 30% reported
      past suicidal ideation and 25% attempts. CONCLUSIONS: NSSI is a significant,
      largely unaddressed mental health problem among the White Mountain Apache Tribe
      and likely other reservation communities, especially as NSSI could serve as a
      precursor to suicide in this population. Interestingly, another self-destructive
      behavior, severe substance use, was reported to the surveillance system by
      Apaches and described in terms similar to NSSI, an important preliminary finding
      worth further exploration.

PMID- 21871369
TI  - Social phobia and subtypes in the national comorbidity survey-adolescent
      supplement: prevalence, correlates, and comorbidity.
AB  - OBJECTIVE: Social phobia typically develops during the adolescent years, yet no
      nationally representative studies in the United States have examined the rates
      and features of this condition among youth in this age range. The objectives of
      this investigation were to: (1) present the lifetime prevalence, sociodemographic
      and clinical correlates, and comorbidity of social phobia in a large, nationally
      representative sample of U.S. adolescents; and (2) examine differences in the
      rates and features of social phobia across the proposed DSM-5 social phobia
      subtypes. METHOD: The National Comorbidity Survey Replication-Adolescent
      Supplement is a nationally representative face-to-face survey of 10,123
      adolescents 13 to 18 years of age in the continental United States. RESULTS:
      Approximately 9% of adolescents met criteria for any social phobia in their
      lifetime. Of these adolescents, 55.8% were affected with the generalized subtype
      and 44.2% exhibited nongeneralized social phobia. Only 0.7% met criteria for the
      proposed DSM-5 performance-only subtype. Generalized social phobia was more
      common among female adolescents and risk for this subtype increased with age.
      Adolescents with generalized social phobia also had a younger age of onset,
      higher levels of disability and clinical severity, and a greater degree of
      comorbidity relative to adolescents with nongeneralized forms of the disorder.
      CONCLUSIONS: This study indicates that social phobia is a highly prevalent,
      persistent, and impairing psychiatric disorder among adolescent youth. Results of
      this study also provide evidence for the clinical utility of the generalized
      subtype and highlight the importance of considering the heterogeneity of social
      phobia in this age group.

PMID- 21871370
TI  - Mental health screening and follow-up care in public high schools.
AB  - OBJECTIVE: Despite increased interest in screening adolescents for mental health
      problems and suicide risk, little is known regarding the extent to which youth
      are identified and connected with appropriate services. METHOD: Between 2005 and
      2009, a total of 4,509 ninth-grade students were offered screening. We reviewed
      the records of the 2,488 students who were screened. Students identified as being
      at risk were provided with a referral. Data were collected on screening results,
      mental health referrals, and completion of recommended treatment over
      approximately 90 days. RESULTS: Among students screened, 19.6% were identified as
      being at risk, 73.6% of whom were not currently receiving any treatment. Students
      referred for school services tended to be less severely ill than those referred
      for community services, with lower rates of suicidal ideation, prior suicide
      attempts, and self-injury. Among at-risk students not currently in treatment,
      76.3% of students referred received at least one mental health visit during the
      follow-up period. Overall, 74.0% of students were referred to school and 57.3% to
      community services. A great majority of school referrals (80.2%) successfully
      accessed services, although a smaller proportion of community services referrals
      successfully accessed treatment (41.9%). CONCLUSIONS: Systematic voluntary school
      based mental health screening and referral offers a feasible means of identifying
      and connecting high-risk adolescents to school- and community-based mental health
      services, although linkages to community-based services may require considerable
      coordination.

PMID- 21871371
TI  - Links between co-occurring social-communication and hyperactive-inattentive trait
      trajectories.
AB  - OBJECTIVE: There is overlap between an autistic and hyperactive-inattentive
      symptomatology when studied cross-sectionally. This study is the first to examine
      the longitudinal pattern of association between social-communication deficits and
      hyperactive-inattentive symptoms in the general population, from childhood
      through adolescence. We explored the interrelationship between trajectories of co
      occurring symptoms, and sought evidence for shared prenatal/perinatal risk
      factors. METHOD: Study participants were 5,383 singletons of white ethnicity from
      the Avon Longitudinal Study of Parents and Children (ALSPAC). Multiple
      measurements of hyperactive-inattentive traits (Strengths and Difficulties
      Questionnaire) and autistic social-communication impairment (Social Communication
      Disorder Checklist) were obtained between 4 and 17 years. Both traits and their
      trajectories were modeled in parallel using latent class growth analysis (LCGA).
      Trajectory membership was subsequently investigated with respect to
      prenatal/perinatal risk factors. RESULTS: LCGA analysis revealed two distinct
      social-communication trajectories (persistently impaired versus low-risk) and
      four hyperactive-inattentive trait trajectories (persistently impaired,
      intermediate, childhood-limited and low-risk). Autistic symptoms were more stable
      than those of attention-deficit/hyperactivity disorder (ADHD) behaviors, which
      showed greater variability. Trajectories for both traits were strongly but not
      reciprocally interlinked, such that the majority of children with a persistent
      hyperactive-inattentive symptomatology also showed persistent social
      communication deficits but not vice versa. Shared predictors, especially for
      trajectories of persistent impairment, were maternal smoking during the first
      trimester, which included familial effects, and a teenage pregnancy. CONCLUSIONS:
      Our longitudinal study reveals that a complex relationship exists between social
      communication and hyperactive-inattentive traits. Patterns of association change
      over time, with corresponding implications for removing exclusivity criteria for
      ASD and ADHD, as proposed for DSM-5.

PMID- 21871372
TI  - Randomized controlled trial of osmotic-release methylphenidate with cognitive
      behavioral therapy in adolescents with attention-deficit/hyperactivity disorder
      and substance use disorders.
AB  - OBJECTIVE: To evaluate the efficacy and safety of osmotic-release methylphenidate
      (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder
      (ADHD), and the impact on substance treatment outcomes in adolescents
      concurrently receiving cognitive-behavioral therapy (CBT) for substance use
      disorders (SUD). METHOD: This was a 16-week, randomized, controlled, multi-site
      trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13 through
      18 years) meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcome
      measures included the following: for ADHD, clinician-administered ADHD Rating
      Scale (ADHD-RS), adolescent informant; for substance use, adolescent-reported
      days of use in the past 28 days. Secondary outcome measures included parent ADHD
      RS and weekly urine drug screens (UDS). RESULTS: There were no group differences
      on reduction in ADHD-RS scores (OROS-MPH: -19.2, 95% confidence interval [CI], 
      17.1 to -21.2; placebo, -21.2, 95% CI, -19.1 to -23.2) or reduction in days of
      substance use (OROS-MPH: -5.7 days, 95% CI, 4.0-7.4; placebo: -5.2 days, 95% CI,
      3.5-7.0). Some secondary outcomes favored OROS-MPH, including lower parent ADHD
      RS scores at 8 (mean difference = 4.4, 95% CI, 0.8-7.9) and 16 weeks (mean
      difference =6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean = 3.8)
      compared with placebo (mean = 2.8; p = .04). CONCLUSIONS: OROS-MPH did not show
      greater efficacy than placebo for ADHD or on reduction in substance use in
      adolescents concurrently receiving individual CBT for co-occurring SUD. However,
      OROS-MPH was relatively well tolerated and was associated with modestly greater
      clinical improvement on some secondary ADHD and substance outcome measures.
      Clinical Trial Registration Information-Attention Deficit Hyperactivity Disorder
      (ADHD) in Adolescents with Substance Use Disorders (SUD);
      http://www.clinicaltrials.gov; NCT00264797.

PMID- 21871373
TI  - A double-blind, placebo-controlled study of risperidone for the treatment of
      adolescents and young adults with anorexia nervosa: a pilot study.
AB  - OBJECTIVE: The purpose of this double-blind, placebo-controlled exploratory pilot
      study was to evaluate the safety and efficacy of risperidone for the treatment of
      anorexia nervosa. METHOD: Forty female subjects 12 to 21 years of age (mean, 16
      years) with primary anorexia nervosa in an eating disorders program were
      randomized to receive risperidone (n = 18) or placebo (n = 22). Subjects
      completed the Eating Disorder Inventory 2, Color-A-Person Test, Body Image
      Software, and Multidimensional Anxiety Scale for Children at baseline and regular
      intervals. Weight, laboratory values, and electrocardiograms were monitored.
      Study medication was started at 0.5 mg daily and titrated upward weekly in 0.5-mg
      increments to a maximum dose of 4 mg until the subject reached a study endpoint.
      RESULTS: The mean dose for the risperidone group was 2.5 mg and for the placebo
      group was 3 mg for a mean duration of 9 weeks. Subjects taking risperidone had a
      significant decrease on the Eating Disorder Inventory 2 Drive for Thinness
      subscale over the first 7 weeks (effect size, 0.88; p = .002), but this
      difference was not sustained to the end of the study (p = .13). The Eating
      Disorder Inventory 2 Interpersonal Distrust subscale decreased significantly more
      in subjects taking risperidone (effect size, 0.60; p = .03). Subjects taking
      risperidone had increased prolactin levels (week 7; p = .001). There were no
      significant differences between groups at baseline or the end of the study for
      the other rating scales, change in weight, or laboratory measurements.
      CONCLUSIONS: This study does not demonstrate a benefit for the addition of
      risperidone in adolescents with anorexia nervosa during the weight-restoration
      phase of care. Clinical trial registration information-A Double-Blind, Placebo
      Controlled Study of Risperidone for the Treatment of Anorexia Nervosa,
      http://www.clinicaltrials.gov, NCT00140426.

PMID- 21871374
TI  - Influence of mental health and substance use problems and criminogenic risk on
      outcomes in serious juvenile offenders.
AB  - OBJECTIVE: To investigate the relations among certain mental health problems
      (MHPs; affective, anxiety, attention-deficit/hyperactivity disorder [ADHD], and
      substance use disorders), criminogenic risk, and outcomes in a sample of serious
      adolescent offenders. METHOD: Using data from a longitudinal study of serious
      adolescent offenders (N = 949; mean age = 16 years, SD = 1.10 years; 84% male;
      78% minority), we evaluated the association of MHPs with three distinct outcomes
      (rearrest, self-reported antisocial activity, and gainful activity), tested
      whether having an MHP contributed any unique explanatory power regarding these
      outcomes over and above criminogenic risk markers, and examined whether MHPs
      moderated the relationship between risk markers and outcomes. Negative binomial
      and ordinal regressions were used. Data for the study were derived primarily from
      youth self-report over a 7-year period, with parent collaterals reporting on
      ADHD, and official records as the source for rearrest information. RESULTS: Of
      the sample, 57.5% met the criteria for at least one of the assessed MPHs. The
      presence of a substance use disorder showed consistent associations with the
      outcomes. After controlling for risk markers and demographic characteristics,
      MHPs were not associated with most outcomes. The co-occurrence of a substance use
      disorder and an MHP moderated the relations between several risk markers and
      outcomes. CONCLUSIONS: Current juvenile justice policies that focus treatment
      efforts on both criminogenic and mental health factors (with particular emphasis
      on treating substance use disorders) appear to be well founded. It is unlikely
      that focusing solely on treating MHPs in serious offenders will have a distinct
      impact on later outcomes.

PMID- 21871377
TI  - The evolving price of perfection.

PMID- 21871375
TI  - Developmental alterations of frontal-striatal-thalamic connectivity in obsessive
      compulsive disorder.
AB  - OBJECTIVE: Pediatric obsessive-compulsive disorder is characterized by
      abnormalities of frontal-striatal-thalamic circuitry that appear near illness
      onset and persist over its course. Distinct frontal-striatal-thalamic loops
      through cortical centers for cognitive control (anterior cingulate cortex) and
      emotion processing (ventral medial frontal cortex) follow unique maturational
      trajectories, and altered connectivity within distinct loops may be
      differentially associated with OCD at specific stages of development. METHOD:
      Altered development of striatal and thalamic connectivity to medial frontal
      cortex was tested in 60 OCD patients compared with 61 healthy control subjects at
      child, adolescent, and adult stages of development, using resting-state
      functional connectivity MRI. RESULTS: OCD in the youngest patients was associated
      with reduced connectivity of dorsal striatum and medial dorsal thalamus to
      rostral and dorsal anterior cingulate cortex, respectively. Increased
      connectivity of dorsal striatum to ventral medial frontal cortex was observed in
      patients at all developmental stages. In child patients, reduced connectivity
      between dorsal striatum and rostral anterior cingulate cortex correlated with OCD
      severity. CONCLUSIONS: Frontal-striatal-thalamic loops involved in cognitive
      control are hypoconnected in young patients near illness onset, whereas loops
      implicated in emotion processing are hyperconnected throughout the illness.

PMID- 21871378
TI  - Celebrating our success.

PMID- 21871379
TI  - Cigarette smoking and foot and ankle surgery.

PMID- 21871380
TI  - Tubercular osteomyelitis of the second metatarsal: a case report.
AB  - A number of studies have described the osteoarticular involvement of
      tuberculosis, but very few cases of tubercular osteomyelitis of the foot have
      been reported. We describe a case of spina ventosa affecting the second
      metatarsal, with a review of the literature and description of the clinical
      manifestations, diagnostic images, and treatment of skeletal tuberculosis.

PMID- 21871382
TI  - Invited commentary.

PMID- 21871383
TI  - Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation
      carriers.

PMID- 21871384
TI  - Sensitivity to alcohol in obese patients: a possible role for food addiction.

PMID- 21871385
TI  - Wedge resection for gastric submucosal tumors.

PMID- 21871387
TI  - Effect of concomitant medical conditions on trauma patients' outcomes.

PMID- 21871388
TI  - Malpractice risk and cost.

PMID- 21871390
TI  - Retraction. Closed loop control of inspired oxygen concentration in trauma
      patients.

PMID- 21871391
TI  - JACS CME featured articles, volume 213, September 2011.

PMID- 21871392
TI  - Thoughts about referrals.

PMID- 21871393
TI  - What is our role in promoting literacy for children who are "blind" or visually
      impaired?

PMID- 21871394
TI  - Visual field screening with a laptop computer system.
AB  - BACKGROUND: The aim of this study was to develop a visual field screening system
      and investigate the importance of using 2 different programs for visual field
      screening to be used in places in which other perimeters are yet not available.
      The system consists of a laptop computer with instructions for the patient
      displayed on the screen and additional equipment to ensure central eye position,
      eye distance to the screen, optimal optical correction, and light intensity. This
      visual field screening system combines a screening program consisting of 68 test
      points with the highest density in areas of high prevalence of visual defects,
      followed by a supplementary program comprising 82 other test points in a
      quadratic lattice pattern. METHODS: The system was compared with Octopus 1-2-3
      threshold perimetry, and the applicability of the system when operated by
      optometrists was evaluated. RESULTS: In the glaucoma clinic at the University
      Hospital, Rigshospitalet, Denmark, the screening program was used to investigate
      98 patients (173 eyes) and to compare the results with those of the Octopus
      Perimetry Program dG2. The sensitivity of the system was 100% and the specificity
      was 78%. Subsequently, 18 optometrists in different locations in Denmark tested
      1,022 patients (2,036 eyes). Patients contacted these optometrists because of the
      presence of refractive error, subjective vision problems, or eye symptoms. The
      screening was used as a part of a routine examination. In 432 eyes (21%), visual
      defects were detected using the screening program. By re-examining 349 eyes, with
      the addition of the supplementary program consisting of 82 other test points in a
      quadratic lattice pattern, the visual field defects were not reproduced in 263
      eyes, a reduction of primary positive visual field defects by 75%. The additional
      supplementary program was not conducted with 38 eyes (2%) because of large visual
      field defects, high intraocular pressures, cataract, positive family history of
      glaucoma, lack of time, or poor patient cooperation. In 56 eyes (3%) examined
      with the additional supplementary program, the defects found in the screening
      program were reproduced. In total, 59 (5.8%) patients (38 + 56 eyes) were
      recommended to pursue an ophthalmologic eye examination by a local
      ophthalmologist. CONCLUSION: Confrontation visual field testing in many places is
      the only method used for examining the visual field. A laptop computer system for
      visual field screening could be a better method for visual field screening in the
      primary eye care setting. For clinical relevance, it is necessary to perform the
      method with 2 different screening programs. The method can be useful as an
      important part of a routine examination and for directing further examinations.

PMID- 21871395
TI  - Safety and compliance of prescription spectacles ordered by the public via the
      Internet.
AB  - BACKGROUND: This study investigated prescription spectacles ordered from online
      vendors and delivered directly to the public for compliance with the optical
      tolerance and impact resistance requirements for eyewear dispensed in the United
      States. METHODS: Ten individuals ordered 2 pairs of spectacles from each of 10 of
      the most visited Internet vendors, totaling 200 eyewear orders. Spectacles
      ordered consisted of ranges of lens and frame materials, lens styles, and
      refractive corrections reflecting current distributions in the United States.
      Evaluations included measurement of sphere power, cylinder power and axis, add
      power (if indicated), horizontal prism imbalance, and impact testing. RESULTS: We
      received and evaluated 154 pairs of spectacles, comprising 308 lenses. Several
      spectacles were provided incorrectly, such as single vision instead of multifocal
      and lens treatments added or omitted. In 28.6% of spectacles, at least 1 lens
      failed tolerance standards for at least 1 optical parameter, and in 22.7% of
      spectacles, at least 1 lens failed impact testing. Overall, 44.8% of spectacles
      failed at least 1 parameter of optical or impact testing. CONCLUSION: Nearly half
      of prescription spectacles delivered directly by online vendors did not meet
      either the optical requirements of the patient's visual needs or the physical
      requirements for the patient's safety.

PMID- 21871396
TI  - Foreword.

PMID- 21871397
TI  - Information technology comes to anesthesiology.

PMID- 21871398
TI  - Anatomy of an anesthesia information management system.
AB  - Anesthesia information management systems (AIMS) have become more prevalent as
      more sophisticated hardware and software have increased usability and
      reliability. National mandates and incentives have driven adoption as well. AIMS
      can be developed in one of several software models (Web based, client/server, or
      incorporated into a medical device). Irrespective of the development model, the
      best AIMS have a feature set that allows for comprehensive management of workflow
      for an anesthesiologist. Key features include preoperative, intraoperative, and
      postoperative documentation; quality assurance; billing; compliance and
      operational reporting; patient and operating room tracking; and integration with
      hospital electronic medical records.

PMID- 21871399
TI  - Anesthesia information management systems marketplace and current vendors.
AB  - This article addresses the brief history of anesthesia information management
      systems (AIMS) and discusses the vendors that currently market AIMS. The current
      market penetration based on the information provided by these vendors is
      presented and the rationale for the purchase of AIMS is discussed. The
      considerations to be evaluated when making a vendor selection are also discussed.

PMID- 21871400
TI  - Clinical research using an information system: the multicenter perioperative
      outcomes group.
AB  - Clinical research using electronic medical record (EMR) data is an emerging
      source of scientific progress. Increasingly, researchers are using retrospective
      observational data acquired from EMRs as the substrate for their clinical
      research into comorbidities, procedures, situations, and outcomes that have
      historically presented significant challenges. Although EMR data collection is
      perceived to require fewer resources than manual chart review, there are many
      specific regulatory, privacy, data quality, and technique issues unique to
      clinical research using EMR data. This article discusses the use of EMRs for
      observational research.

PMID- 21871401
TI  - Real-time alerts and reminders using information systems.
AB  - Adoption of information systems throughout the hospital environment has enabled
      the development of real-time physiologic alerts and clinician reminder systems.
      These clinical tools can be made available through the deployment of anesthesia
      information management systems (AIMS). Creating usable alert systems requires
      understanding of technical considerations. Various successful implementations are
      reviewed, encompassing cost reduction, improved revenue capture, timely
      antibiotic administration, and postoperative nausea and vomiting prophylaxis.
      Challenges to the widespread use of real-time alerts and reminders include AIMS
      adoption rates and the difficulty in choosing appropriate areas and approaches
      for information systems support.

PMID- 21871402
TI  - Shortcomings and challenges of information system adoption.
AB  - The number of institutions implementing AIMS is increasing. Shortcomings in the
      design and implementation of EMRs have been associated with unanticipated
      consequences, including changes in workflow. These have often resulted from the
      carryover of paper-based documentation practices into an electronic environment.
      The new generation of mobile devices allows providers to have situational
      awareness of multiple care sites simultaneously, possibly allowing for improved
      proactive decision making. Although potentially facilitating safer anesthetic
      supervision, technologic and cultural barriers remain. Security, quality of
      information delivery, regulatory issues, and return on investment will continue
      as challenges in implementing and maintaining this new technology.

PMID- 21871403
TI  - Creating a real return-on-investment for information system implementation: life
      after HITECH.
AB  - In 2010, the Centers for Medicare and Medicaid Services (CMS) published its final
      rule describing plans for incentivizing eligible professionals (EPs) and eligible
      hospitals to become meaningful users of electronic health record (EHR) technology
      using funds provided by the Health Information Technology for Economic and
      Clinical Health (HITECH) Act. Beginning in 2011, non-hospital-based EPs can earn
      monetary benefits for meeting meaningful use criteria through implementation of
      certified EHR technology. Most anesthesiologists qualify as non-hospital-based
      EPs under CMS' new hospital-based definition. The authors distill CMS' final rule
      into its most basic facts and requirements and explain the implications for US
      anesthesiologists.

PMID- 21871404
TI  - Quality improvement using automated data sources: the anesthesia quality
      institute.
AB  - The Anesthesia Quality Institute has created the National Anesthesia Clinical
      Outcomes Registry to automatically capture electronic data specific to anesthesia
      cases. Data come from billing systems, quality management systems, hospital
      electronic health care records, and anesthesia information management systems.
      Aggregation of this data will allow for calculation of national and cohort
      specific benchmarks for anesthesia outcomes of interest. Provision of this data
      to anesthesia practitioners through periodic private reports will motivate
      improvements in the quality of care.

PMID- 21871405
TI  - Integration of the enterprise electronic health record and anesthesia information
      management systems.
AB  - Fewer than 5% of anesthesia departments use an electronic medical record (EMR)
      that is anesthesia specific. Many anesthesia information management systems
      (AIMS) have been developed with a focus only on the unique needs of anesthesia
      providers, without being fully integrated into other electronic health record
      components of the entire enterprise medical system. To understand why anesthesia
      providers should embrace health information technology (HIT) on a health system
      wide basis, this article reviews recent HIT history and reviews HIT concepts. The
      author explores current developments in efforts to expand enterprise HIT, and the
      pros and cons of full enterprise integration with an AIMS.

PMID- 21871406
TI  - Advanced integrated real-time clinical displays.
AB  - Intelligent medical displays have the potential to improve patient outcomes by
      integrating multiple physiologic signals, exhibiting high sensitivity and
      specificity, and reducing information overload for physicians. Research findings
      have suggested that information overload and distractions caused by patient care
      activities and alarms generated by multiple monitors in acute care situations,
      such as the operating room and the intensive care unit, may produce situations
      that negatively impact the outcomes of patients under anesthesia. This can be
      attributed to shortcomings of human-in-the-loop monitoring and the poor
      specificity of existing physiologic alarms. Modern artificial intelligence
      techniques (ie, intelligent software agents) are demonstrating the potential to
      meet the challenges of next-generation patient monitoring and alerting.

PMID- 21871407
TI  - Enhancing point of care vigilance using computers.
AB  - Information technology has the potential to provide a tremendous step forward in
      perioperative patient safety. Through automated delivery of information through
      fixed and portable computer resources, clinicians may achieve improved
      situational awareness of the overall operation of the operating room suite and
      the state of individual patients in various stages of surgical care. Coupling the
      raw, but integrated, information with decision support and alerting algorithms
      enables clinicians to achieve high reliability in documentation compliance and
      response to care protocols. Future studies and outcomes analysis are needed to
      quantify the degree of benefit of these new components of perioperative
      information systems.

PMID- 21871408
TI  - The use of computers for perioperative simulation in anesthesia, critical care,
      and pain medicine.
AB  - Simulation in perioperative anesthesia training is a field of considerable
      interest, with an urgent need for tools that reliably train and facilitate
      objective assessment of performance. This article reviews the available
      simulation technologies, their evolution, and the current evidence base for their
      use. The future directions for research in the field and potential applications
      of simulation technology in anesthesia, critical care, and pain medicine are
      discussed.

PMID- 21871409
TI  - Amiodarone supplants lidocaine in ACLS and CPR protocols.
AB  - Amiodarone is an antiarrhythmic medication used to treat and prevent certain
      types of serious, life-threatening ventricular arrhythmias. Amiodarone gained
      slow acceptance outside the specialized field of cardiac antiarrhythmic surgery
      because the side-effects are significant. Recent adoption of amiodarone in the
      ACLS (Advanced Cardiac Life Support) protocol has somewhat popularized this class
      of antiarrhythmics. Its use is slowly expanding in the acute medicine setting of
      anesthetics. This article summarizes the use of Amiodarone by anesthesiologists
      in the operating room and during cardiopulmonary resuscitation.

PMID- 21871410
TI  - Voluven, a new colloid solution.
AB  - Hydroxyethyl starch (HES) 130/0.4 (Voluven, Fresenius/Hospira, Germany) is
      indicated for the treatment and prophylaxis of hypovolemia. As the Voluven
      molecule is smaller than those of other available hydroxyethyl starch products,
      it is associated with less plasma accumulation and can be safely used in patients
      with renal impairment. Previous studies have demonstrated that Voluven has
      comparable effects on volume expansion and hemodynamics as other available HES
      products. Voluven is also associated with fewer effects on coagulation and may be
      an acceptable alternative to albumin for volume expansion in situations in which
      other starches are contraindicated secondary to risk of coagulopathy.

PMID- 21871411
TI  - Rehabilitation confronts technology: knowing how to manage innovations and
      expectations.

PMID- 21871412
TI  - Postacute care and ischemic stroke mortality: findings from an integrated health
      care system in northern California.
AB  - OBJECTIVE: To study the association of postacute care (PAC) settings and
      mortality outcome of patients who sustained an ischemic stroke. DESIGN: A
      retrospective cohort study. SETTING: An integrated health care system in northern
      California. PARTICIPANTS: Patients who sustained an acute ischemic stroke between
      1996 and 2004, survived the initial acute care hospital stay, and received PAC
      services within 14 days of discharge (n = 16,538) and 61 days of discharge (n =
      16,468). INTERVENTIONS: PAC rehabilitation ranked by resource level, that is,
      inpatient rehabilitation hospital (IRH), skilled nursing facility (SNF), home
      health (HH), and outpatient (OP) rehabilitation. MAIN OUTCOME MEASUREMENTS: One
      year mortality after acute care hospital discharge. RESULTS: The highest level of
      PAC services received within 14 days of acute care discharge was IRH for 5.6% of
      patients, SNF for 48.3% of patients, HH for 18.9% of patients, and OP for 27.3%
      of patients. The highest level of PAC services received within 61 days of acute
      care discharge was IRH for 10.9% of patients, SNF for 40.4% of patients, HH for
      19.1% of patients, and OP for 29.6% of patients. Cox proportional hazard models
      showed that patients whose highest level of PAC service was provided by an IRH,
      through HH, or OP had a significantly better 1-year survival than did those
      admitted to an SNF. The following factors were associated with a higher risk of 1
      year mortality: older age, male gender, African American ethnicity, history of
      previous stroke, higher Deyo-Charlson comorbidity scores, a longer acute care
      hospital stay, and hospitalization in one remotely located health service area.
      CONCLUSIONS: In the year after a stroke occurred, the rate of patient survival
      varied based on PAC rehabilitation services. Age, gender, race or ethnicity,
      history of a previous stroke, comorbid conditions, and service area also were
      significantly associated with 1-year mortality after acute care discharge.
      Further investigation of the differences in mortality among PAC settings is
      indicated.

PMID- 21871413
TI  - Finis origine pendet: commentary on "Postacute care and ischemic stroke
      mortality: findings from an integrated health care system in northern
      California".

PMID- 21871414
TI  - Prolotherapy versus corticosteroid injections for the treatment of lateral
      epicondylosis: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy of prolotherapy versus corticosteroid
      injection for the treatment of chronic lateral epicondylosis. DESIGN: A
      prospective, randomized controlled, double-blinded study. SETTING: Academic,
      tertiary, outpatient, rehabilitation hospital. PARTICIPANTS: Twenty-four subjects
      with clinically determined chronic (ie, lasting 3 months or longer) lateral
      epicondylosis were recruited. All subjects noted pain intensity levels
      significant enough to prevent the participation in activities, such as playing
      racquet sports or lifting heavy objects. METHODS: Subjects were assigned to
      receive either prolotherapy or corticosteroid injection for treatment of chronic
      lateral epicondylosis. Each subject underwent injection at baseline followed by a
      second injection 1 month later. OUTCOME MEASUREMENTS: Visual analog scale (VAS)
      self-rating of pain, quadruple visual analog scale (QVAS), and the Disabilities
      of the Arm, Shoulder, and Hand questionnaire (DASH) were measured at baseline and
      at 1, 3, and 6 months' follow-up. RESULTS: Within each group, the analysis
      demonstrated statistically significant improvements in both VAS and DASH within
      the prolotherapy group with significant changes noted from baseline to 3 months
      (VAS: Delta2.38; 95% confidence interval [95% CI] 1.04-3.71, P = .004 and DASH:
      Delta19.89; 95% CI 5.73-34.04, P = .01), and baseline to 6 months (VAS:
      Delta2.63; 95% CI 0.61-4.62, P = .017 and DASH: Delta21.76; 9% CI 7.43-36.09, P =
      .009) after initial treatment, as well as in the QVAS from baseline to 3 months.
      The steroid group demonstrated a clinically and statistically significant change
      for DASH only at both 3-month (Delta13.33; 95% CI 0.68-25.99, P = .04) and 6
      month (Delta15.56; 95% CI 1.30-29.81, P = .04) follow-up. Comparison of the
      subjects completing the study revealed no significant differences between the
      prolotherapy and the corticosteroid group for change in VAS, QVAS, or DASH,
      although the study lacked sufficient power to draw conclusions from this finding.
      Eighty-three percent of the subjects were satisfied with their overall
      improvement during the course of the study, without significant differences
      revealed between groups. Aside from injection-associated pain, no adverse
      reactions were reported. Seventeen subjects completed study protocol.
      CONCLUSIONS: Both prolotherapy and corticosteroid therapy were generally well
      tolerated and appeared to provide benefit of long duration. Small sample size
      precludes determining whether one therapy is superior to the other. Larger,
      controlled trials appear feasible and warranted on the basis of these findings.

PMID- 21871415
TI  - Stroke rehabilitation in Australia in a freestanding inpatient rehabilitation
      unit compared with a unit located in an acute care hospital.
AB  - OBJECTIVE: To study the functional outcome of stroke rehabilitation from 2 units
      that are similar in most aspects except for location: freestanding rehabilitation
      units (FSRU) versus acute care hospital (acute hospital rehabilitation unit
      [AHRU]). DESIGN: An observational retrospective cohort study. SETTING:
      Rehabilitation units in university-affiliated hospitals in Australia. METHODS:
      Five-year data on functional outcomes of stroke rehabilitation and rehabilitation
      process measures from an FSRU were compared with data from the subsequent 5 years
      after the same unit was relocated to an AHRU. MAIN OUTCOME MEASUREMENTS: Time
      from stroke onset to rehabilitation assessment, time to transfer to
      rehabilitation, length of stay (LOS), Functional Independence Measure (FIM)
      score, Motor Assessment Scale (MAS) score, transfer back to acute care, walking
      velocity, and discharge destination. RESULTS: Data on 357 patients from an FSRU
      and 372 patients from an AHRU who completed the rehabilitation program are
      presented. Baseline characteristics, such as age, gender, stroke location, stroke
      type, and risk factors, were similar in the 2 groups. There was no difference in
      outcomes such as FIM score, MAS score, walking velocity, or discharge
      destination. On regression analysis, the patients in an FSRU had a longer LOS
      (37.6 versus 35.9 days) and were more likely to be transferred to acute care than
      from an AHRU (12.4% versus 5.4%). The episode LOS (total LOS in acute and
      rehabilitation units) was nearly identical in the 2 settings at 52.6 days (15 in
      acute care + 37.6 days in an FSRU and 16.7 in acute care + 35.9 days in an AHRU).
      CONCLUSIONS: Stroke rehabilitation effectiveness is not related to the proximity
      of a rehabilitation facility to acute medical services. However, the increased
      need for the transfer of patients with medical complications from FSRU to acute
      care, longer LOS in an FSRU, and greater difficulty in obtaining consultations
      from other medical specialties persuade us to recommend a unit co-located with
      acute care services instead of an FSRU.

PMID- 21871416
TI  - Test-retest reliability of the Sensory Organization Test in older persons with a
      transtibial amputation.
AB  - OBJECTIVE: To determine the test-retest reliability of the Sensory Organization
      Test (SOT) in older persons with a unilateral transtibial amputation. DESIGN:
      Cross-sectional observational study with repeated measures. SETTING: A University
      balance laboratory. PARTICIPANTS: Fifteen participants (12 men and 3 women) who
      had undergone a unilateral transtibial amputation that was performed as a result
      of either trauma or complications of diabetes or peripheral vascular disease were
      recruited from a patient database. The mean age of the participants was 69.53
      years (SD, 6.60), with 11.94 mean years of prosthetic use. INTERVENTION: All
      participants completed 3 trials of the 6 balance testing conditions in the
      standard SOT protocol with use of the NeuroCom SMART Equitest system on 2
      occasions approximately 2 weeks apart. MAIN OUTCOME MEASURES: Reliability of the
      mean equilibrium and strategy scores for the 6 SOT conditions and the overall
      composite score was evaluated using intraclass correlation coefficients. RESULTS:
      The test-retest reliability coefficients (intraclass correlation coefficient
      model 2,1) for the equilibrium scores ranged from 0.67-0.90 for conditions 1 to 4
      and 6, indicating fair-to-good reliability. The coefficients obtained for the
      strategy scores of all the conditions and the composite score showed excellent
      reliability (intraclass correlation coefficients >0.75). CONCLUSIONS: This study
      suggests that the majority of outcome measurements associated with the SOT
      protocol on the SMART Equitest provide a reliable measure of dynamic balance
      performance in older persons with a unilateral transtibial amputation, even in
      the presence of comorbidities. The equilibrium, strategy, and composite scores
      obtained from the testing protocol with the exception of condition 5, can be used
      reliably in clinical practice to monitor for changes in balance with
      rehabilitation or to monitor the effects of a specific intervention and/or in
      patients with comorbidities that could potentially affect their balance
      capacities.

PMID- 21871417
TI  - Targeted preventive care may be needed for adults with congenital spine
      anomalies.
AB  - OBJECTIVE: To compare hospitalizations caused by spina bifida-sensitive
      conditions, ambulatory care-sensitive conditions in adults with spina bifida and
      in the general population, our aim was to provide information about whether
      preventive health efforts already underway in the hospitalized general population
      are adequate for preventive care in spina bifida and congenital spine anomalies.
      DESIGN: Retrospective secondary data analysis. PATIENTS (OR PARTICIPANTS):
      Records of hospitalized individuals who were 18 years of age and older. METHODS:
      Comparison between individuals hospitalized with spina bifida and the general
      population using data from the California State Inpatient Database from the
      Healthcare Cost and Utilization Project for 2004 of adults. MAIN OUTCOME
      MEASUREMENTS: Prevalence of spina bifida-sensitive conditions and ambulatory care
      sensitive conditions as reason for hospitalization and 30-day readmission.
      RESULTS: As compared with the general population, persons with spina bifida who
      were hospitalized in 2004 had a significantly greater number of hospitalizations,
      number of hospitalizations associated with both spina bifida-sensitive conditions
      and ambulatory care-sensitive conditions, and number of 30-day readmissions.
      Stratification by age shows that the admissions for spina bifida sensitive
      conditions were greater in persons with spina bifida than in the general
      population for all age groups. In contrast, only in the youngest age group did
      those with spina bifida experience greater hospitalizations for ambulatory care
      sensitive conditions. CONCLUSIONS: This study provides further evidence that
      persons with spina bifida have hospitalizations that are beyond what the general
      population experiences. These conditions may be potentially preventable with
      appropriate ambulatory care. This group also had a greater risk for readmission
      within 30 days of discharge from their last hospitalization. More research is
      needed on the efficacy of programs aimed at prevention of these conditions.

PMID- 21871418
TI  - Kinetic chains: a review of the concept and its clinical applications.
AB  - During the past decade, our understanding of biomechanics and its importance in
      rehabilitation has advanced significantly. The kinetic chain, a concept borrowed
      from engineering, has helped us better understand the underlying physiology of
      human movement. This understanding, in turn, has facilitated the development of
      new and more rational rehabilitation strategies. The kinetic chain concept has
      application in a wide spectrum of clinical conditions, including musculoskeletal
      medicine, sports medicine, and neurorehabilitation, as well as prosthetics and
      orthotics. The purpose of this review is to provide insights into the
      biomechanics related to the concept of kinetic chains, with a specific focus on
      closed kinetic chains and its clinical applications in rehabilitation.

PMID- 21871419
TI  - Inpatient rehabilitation of patients with cancer: efficacy and treatment
      considerations.
AB  - Although cancer can affect a great number of individuals and is the second
      leading cause of death in the United States, the number of individuals admitted
      to acute inpatient rehabilitation units with impairments primarily as the result
      of cancer diagnoses remains small. There is a lack of awareness among health care
      providers as to the functional loss that can be associated with cancer and the
      potential benefits of inpatient rehabilitation. Furthermore, financial pressures
      from third-party payors may dissuade the admission of patients with cancer for
      inpatient rehabilitation. This is a narrative review of the literature with
      respect to the efficacy and potential benefits of inpatient rehabilitation for
      patients with cancer. The findings of studies on the rehabilitation of general
      cancer populations are presented, with a focus on functional outcomes, medical
      complications and transfer rates, and common symptoms encountered during
      inpatient rehabilitation. Studies that focus on tumors involving the brain and
      spinal cord are separately analyzed. Functional outcomes by tumor location are
      reviewed with respect to tumor type, recurrence, and comparison with nontumor
      diagnoses. In addition, the effects of concomitant treatments on functional
      outcomes and possible correlations of survival with functional outcome are
      presented. Justification for admission of patients with cancer diagnoses to
      inpatient rehabilitation units, as well as implications for management of these
      patients during their rehabilitation stay, will be summarized.

PMID- 21871420
TI  - What will meaningful use mean to your practice?

PMID- 21871421
TI  - Pelvic floor pain: physical therapy versus injections.

PMID- 21871422
TI  - Bertolotti syndrome as a potential cause of low back pain in golfers.

PMID- 21871423
TI  - Evaluation and treatment of anterolateral ankle impingement syndrome.

PMID- 21871424
TI  - Pectoral muscle spasms after mastectomy successfully treated with botulinum toxin
      injections.

PMID- 21871425
TI  - Adverse host factors exacerbate occult HIV-associated nephropathy.
AB  - In the present study, we hypothesized that HIV-1-induced occult HIV-associated
      nephropathy (HIVAN) would become apparent in the presence of adverse host
      factors. To test our hypothesis, Vpr mice (which display doxycycline-dependent
      Vpr expression in podocytes) with two, three, and four copies of the
      angiotensinogen (Agt) gene (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were
      administered doxycycline for 3 weeks (to develop clinically occult HIVAN)
      followed by doxycycline-free water during the next 3 weeks. Subsequently, renal
      biomarkers were measured, and kidneys were harvested for renal histology. Vpr-Agt
      2 developed neither proteinuria nor elevated blood pressure, and displayed
      minimal glomerular and tubular lesions only, without any microcyst formation. Vpr
      Agt-3 showed mild glomerular and tubular lesions and microcyst formation, whereas
      Vpr-Agt-4 showed moderate proteinuria, hypertension, glomerular sclerosis,
      tubular dilation, microcysts, and expression of epithelial mesenchymal transition
      markers. Vpr-Agt-4 not only displayed enhanced renal tissue expression of Agt,
      renin, and angiotensin-converting enzyme, but also had higher renal tissue
      concentrations of angiotensin II. Moreover, renal cells in Vpr-Agt-4 showed
      enhanced expression of transforming growth factor-beta, connective tissue growth
      factor, and vascular endothelial growth factor. These findings indicate that
      adverse host factors, such as the activation of the renin-angiotensin system,
      promote the progression of occult HIVAN to apparent HIVAN.

PMID- 21871426
TI  - p52 Activation in monomorphic B-cell posttransplant lymphoproliferative
      disorder/diffuse large B-cell lymphoma without BAFF-R expression.
AB  - Posttransplantation lymphoproliferative disorders (PTLD) are associated with
      Epstein-Barr virus (EBV) and activate the NF-kappaB pathway. B-cell activating
      factor (BAFF) modulates cell growth and survival in non-Hodgkin's lymphomas.
      However, there are few studies of EBV, BAFF/BAFF-R signaling, and NF-kappaB1 and
      NF-kappaB2 pathway activation in PTLD. Diffuse large B-cell lymphomas (DLBCL) in
      two different clinical contexts, immunocompetent patients (DLBCL/IC; n = 30) or
      posttransplantation solid-organ recipients (DLBCL/PTLD; n = 21), were
      characterized histogenically as germinal center (GC) or non-germinal center
      (NGC). Expression of BAFF, BAFF-R, and NF-kappaB proteins p50 and p52 and the
      presence or absence of EBV were compared in these clinical contexts. Regardless
      of the GC or NGC pattern of DLBCL, BAFF-R was expressed in 37% of DLBCL/IC but in
      only 4.8% of DLBCL/PTLD. p52 was expressed in DLBCL/PTLD/NGC (12 of 19 cases) as
      compared with DLBCL/IC/NGC (0 of 18 cases). This pattern might be related to the
      presence of EBV and latent membrane protein 1 because p52 expression was observed
      primarily in EBV-positive DLBCL/PTLD cases expressing latent membrane protein 1.
      Thus, the activation profile or NGC pattern of DLBCL/PTLD was not associated with
      BAFF/BAFF-R expression, whereas nuclear p52 related to NF-kappaB2 pathway
      activation might be linked to EBV.

PMID- 21871428
TI  - Silencing of the imprinted DLK1-MEG3 locus in human clinically nonfunctioning
      pituitary adenomas.
AB  - DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed
      noncoding RNA genes and paternally expressed protein-coding genes. The expression
      of maternally expressed gene 3 (MEG3) is selectively lost in clinically
      nonfunctioning adenomas (NFAs) of gonadotroph origin; however, expression status
      of other genes at this locus in human pituitary adenomas has not previously been
      reported. Using quantitative real-time RT-PCR, we evaluated expression of 24
      genes from the DLK1-MEG3 locus in 44 human pituitary adenomas (25 NFAs, 7 ACTH
      secreting, 7 GH-secreting, and 5 PRL-secreting adenomas) and 10 normal
      pituitaries. The effects on cell proliferation of five miRNAs whose expression
      was lost in NFAs were investigated by flow cytometry analysis. We found that 18
      genes, including 13 miRNAs at the DLK1-MEG3 locus, were significantly down
      regulated in human NFAs. In ACTH-secreting and PRL-secreting adenomas, 12 and 7
      genes were significantly down-regulated, respectively; no genes were
      significantly down-regulated in GH-secreting tumors. One of the five miRNAs
      tested induced cell cycle arrest at the G2/M phase in PDFS cells derived from a
      human NFA. Our data indicate that the DLK1-MEG3 locus is silenced in NFAs. The
      growth suppression by miRNAs in PDFS cells is consistent with the hypothesis that
      the DLK1-MEG3 locus plays a tumor suppressor role in human NFAs.

PMID- 21871427
TI  - Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) may be triggered by epithelial injury that
      results in aberrant production of growth factors, cytokines, and proteinases,
      leading to proliferation of myofibroblasts, excess deposition of collagen, and
      destruction of the lung architecture. The precise mechanisms and key signaling
      mediators responsible for this aberrant repair process remain unclear. We
      assessed the importance of matrix metalloproteinase-3 (MMP-3) in the pathogenesis
      of IPF through i) determination of MMP-3 expression in patients with IPF, ii) in
      vivo experiments examining the relevance of MMP-3 in experimental models of
      fibrosis, and iii) in vitro experiments to elucidate possible mechanisms of
      action. Gene expression analysis, quantitative RT-PCR, and Western blot analysis
      of explanted human lungs revealed enhanced expression of MMP-3 in IPF, compared
      with control. Transient adenoviral vector-mediated expression of recombinant MMP
      3 in rat lung resulted in accumulation of myofibroblasts and pulmonary fibrosis.
      Conversely, MMP-3-null mice were protected against bleomycin-induced pulmonary
      fibrosis. In vitro treatment of cultured lung epithelial cells with purified MMP
      3 resulted in activation of the beta-catenin signaling pathway, via cleavage of E
      cadherin, and induction of epithelial-mesenchymal transition. These processes
      were inhibited in bleomycin-treated MMP-3-null mice, as assessed by cytosolic
      translocation of beta-catenin and cyclin D1 expression. These observations
      support a novel role for MMP-3 in the pathogenesis of IPF, through activation of
      beta-catenin signaling and induction of epithelial-mesenchymal transition.

PMID- 21871429
TI  - Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals.
AB  - We detected HIV-1 DNA in pure populations of perivascular macrophages,
      parenchymal microglia, and astrocytes, isolated using laser microdissection from
      brain tissue of five untreated individuals who died in the presymptomatic stage
      of infection from non-HIV causes. HIV-1 DNA was detected in the three cell
      populations, most consistently in perivascular macrophages, without evidence of
      productive infection. The percentage of PCR reactions detecting HIV-1 DNA in
      perivascular macrophages correlated inversely with peripheral blood CD4 counts.
      These findings demonstrate that brain cell reservoirs of latent HIV-1 exist
      before pathological HIV encephalitis and suggest that perivascular macrophage
      trafficking of latent virus into the brain increases with immunosuppression.

PMID- 21871430
TI  - A new electrochemical biosensor for DNA detection based on molecular recognition
      and lead sulfide nanoparticles.
AB  - In this paper, we constructed a new electrochemical biosensor for DNA detection
      based on a molecule recognition technique. In this sensing protocol, a novel dual
      labeled DNA probe (DLP) in a stem-loop structure was employed, which was designed
      with dabcyl labeled at the 3' end as a guest molecule, and with a Pb nanoparticle
      labeled at the 5' end as electrochemical tag to indicate hybridization. One alpha
      cyclodextrin-modified electrode (alpha-CD/MCNT/GCE) was used for capturing the
      DNA hybridization. Initially, the DLP was in the "closed" state in the absence of
      the target, which shielded dabcyl from the bulky alpha-CD/MCNT/GCE conjugate due
      to a steric effect. After hybridization, the loop sequence (16 bases) formed a
      rigid duplex with the target, breaking the relatively shorter stem duplex (6
      bases). Consequently, dabcyl was forced away from the Pb nanoparticle and became
      accessible by the electrode. Therefore, the target hybridization event can be
      sensitively transduced via detecting the electrochemical reduction current signal
      of Pb. Using this method, as low as 7.1*10(-10)M DNA target had been detected
      with excellent differentiation ability for even a single mismatch.

PMID- 21871431
TI  - Optimal concentrations of N-decanoyl-N-methylglucamine and sodium dodecyl sulfate
      allow the extraction and analysis of membrane proteins.
AB  - We studied the extraction and analysis of integral membrane proteins possessing
      hydrophobic and hydrophilic domains and found that a nonionic detergent called
      MEGA-10, used in lysis buffers, had a superior extraction effect compared to most
      conventional detergents. A sodium dodecyl sulfate (SDS) concentration of >0.4%
      (w/v) in the sample buffer was crucial for those proteins to be clearly analyzed
      by electrophoresis and Western blotting. Furthermore, MEGA-10 had the tendency to
      maximally extract proteins around its critical micelle concentration (CMC) of
      0.24% (w/v). These solutions can greatly assist functional investigations of
      membrane proteins in the proteomics era.

PMID- 21871432
TI  - Development of mass cytometry methods for bacterial discrimination.
AB  - Fluorescent flow cytometry has become the method of choice for interrogation of
      bacterial populations at the single-cell level. However, limitations of this
      technique include issues of dynamic range, spectral overlap, photobleaching, and
      overall low signal intensity due to the small size of bacteria. The recent
      development of mass cytometry allows single-cell analysis with the resolution of
      inductively coupled plasma mass spectrometry, facilitating multiparametric
      analysis. Using a combination of a metal-based membrane stain and lectins
      conjugated to lanthanide-chelating polymers, we demonstrate that individual
      Escherichia coli cells can be differentiated based on their cell surface
      polysaccharides using mass cytometry. The model E. coli system involves
      evaluation of three different surface polysaccharides using element-tagged
      concanavalin A and wheat germ agglutinin lectins. Finally, this technique enabled
      experiments designed to follow the export of O-antigen substituted
      lipopolysaccharide in a conditional mutant. These studies revealed that the
      culture responds as a uniform population and that lipopolysaccharide export is
      approximately 10 times faster than the logarithmic bacterial doubling time.

PMID- 21871433
TI  - Cytochrome c oxidase: charge translocation coupled to single-electron partial
      steps of the catalytic cycle.
AB  - The paper presents a survey of time-resolved studies of charge translocation by
      cytochrome c oxidase coupled to transfer of the 1st, 2nd 3rd and 4th electrons in
      the catalytic cycle. Single-electron photoreduction experiments carried out with
      the A-class cytochrome c oxidases of aa(3) type from mitochondria, Rhodobacter
      sphaeroides and Paracoccus denitrificans as well as with the ba(3)-type oxidase
      from Thermus thermophilus indicate that the protonmotive mechanisms, although
      similar, may not be identical for different partial steps in the same enzyme
      species, as well as for the same single-electron transition in different
      oxidases. The pattern of charge translocation coupled to transfer of a single
      electron in the A-class oxidases confirms major predictions of the original model
      of proton pumping by cytochrome oxidase [Artzatbanov, V. Y., Konstantinov, A. A.
      and Skulachev, V.P. "Involvement of Intramitochondrial Protons in Redox Reactions
      of Cytochrome a." FEBS Lett. 87: 180-185]. The intermediates and partial
      electrogenic steps observed in the single-electron photoreduction experiments may
      be very different from those observed during oxidation of the fully reduced
      oxidase by O(2) in the "flow-flash" studies. .

PMID- 21871434
TI  - Distribution and shedding of the membrane phosphatidylserine during maturation
      and aging of erythroid cells.
AB  - Maturation and aging of erythroid cells are accompanied by extensive remodeling
      of the membrane and a marked decrease in cell size, processes that are mediated
      by externalization and shedding of phosphatidylserine (PS). In the present study,
      we investigated the redistribution of PS in the plasma membrane of erythroid
      precursors during their maturation and of mature RBCs during senescence, and the
      involvement of changes in calcium (Ca)-flux in these processes. Maturation was
      studied by analyzing normal human bone marrow cells as well as cultured human
      normal erythroid precursors induced by erythropoietin and murine erythroleukemia
      cells induced by hexamethylene-bisacetamide. Senescence was studied in normal
      human peripheral RBCs following density fractionation. PS and Ca were determined
      by flow cytometry using annexin-V and Flu-3, respectively. The outer, inner and
      shed PS were quantified by a novel two-step binding inhibitory assay. The results
      indicate a bi-phasic modulation of intracellular Ca and PS
      externalization/shedding; both of which decreased during maturation and increased
      during aging. The role of intracellular Ca in PS externalization/shedding was
      demonstrated by modulating intracellular Ca: Ca was decreased by incubating the
      cells with an ion chelator (EDTA) or with decreasing concentrations of Ca,
      whereas treatment with the ionophore A23187 elevated intracellular Ca. The
      results showed that low Ca resulted in decreased outer and shed PS, whereas high
      Ca had the opposite effect. The results suggest that PS externalization and
      shedding are mediated by increased cellular Ca-flux, and that they play an
      important role in erythroid maturation and RBC senescence.

PMID- 21871436
TI  - Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B).
AB  - Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral
      membrane of alpha-intercalated cells of the kidney collecting duct leads to the
      defect of the Cl(-)/HCO(3)(-) exchange and the failure of proton (H(+)) secretion
      at the apical membrane of these cells, causing distal renal tubular acidosis
      (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A
      adaptor complex. However, it is not known whether kAE1 interacts with motor
      proteins in its trafficking process to the plasma membrane or not. We report here
      that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a
      dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction.
      We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney
      tissues and the suppression of endogenous KIF3B in HEK293T cells by small
      interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its
      intracellular accumulation. All results suggest that KIF3B is involved in the
      trafficking of kAE1 to the plasma membrane of human kidney alpha-intercalated
      cells.

PMID- 21871437
TI  - An information integration model of the primary visual cortex under grating
      stimulations.
AB  - During the course of information processing, a visual system extracts
      characteristic information of the visual image and integrates the spatial and
      temporal visual information simultaneously. In this study, we investigate the
      integration effect of neurons in the primary visual cortex (V1 area) under the
      grating stimulation. First, an information integration model was established
      based on the receptive field properties of the extracted features of the visual
      images features, the interaction between neurons and the nonlinear integration of
      those neurons. Then the neuropsychological experiments were designed both to
      provide parameters for the model and to verify its effect. The experimental
      results with factual visual image were largely consistent with the model's
      forecast output. This demonstrates that our model can truly reflect the
      integration effect of the primary visual system when being subjected to grating
      stimulations with different orientations. Our results indicate the primary visual
      system integrates the visual information in the following manner: it first
      extracts visual information through different types of receptive field, and then
      its neurons interact with each other in a non-linear manner, finally the neurons
      fire spikes recorded as responses to the visual stimulus.

PMID- 21871438
TI  - Generation of Sprn-regulated reporter mice reveals gonadic spatial expression of
      the prion-like protein Shadoo in mice.
AB  - The protein Shadoo (Sho) is a paralogue of prion protein, and encoded by the gene
      Sprn. Like prion protein it is primarily expressed in central nervous system, and
      has been shown to have a similar expression pattern in certain regions of the
      brain. We have generated reporter mice carrying a transgene encompassing the Sprn
      promoter, exon 1, intron 1 and the 5'-end of exon 2 driving expression of either
      the LacZ or GFP reporter gene to study the expression profile of Shadoo in mice.
      Expression of the reporter genes was analysed in brains of these transgenic mice
      and was shown to mimic that of the endogenous gene expression, previously
      described by Watts et al. [1]. Consequently, the Sprn-LacZ mice were used to
      study the spatial expression of Sho in other tissues of the adult mouse. Several
      tissues were collected and stained for beta-gal activity, including the thymus,
      heart, lung, liver, kidney, spleen, intestine, muscle, and gonads. From this
      array of tissues, the transgene was consistently expressed only in specific cell
      types of the testicle and ovary, suggesting a role for Shadoo in fertility and
      reproduction. These mice may serve as a useful tool in deciphering the regulation
      of the prion-like gene Sprn and thus, indirectly, of the Shadoo protein.

PMID- 21871435
TI  - Gap junctions in inherited human disorders of the central nervous system.
AB  - CNS glia and neurons express connexins, the proteins that form gap junctions in
      vertebrates. We review the connexins expressed by oligodendrocytes and
      astrocytes, and discuss their proposed physiologic roles. Of the 21 members of
      the human connexin family, mutations in three are associated with significant
      central nervous system manifestations. For each, we review the phenotype and
      discuss possible mechanisms of disease. Mutations in GJB1, the gene for connexin
      32 (Cx32) cause the second most common form of Charcot-Marie-Tooth disease
      (CMT1X). Though the only consistent phenotype in CMT1X patients is a peripheral
      demyelinating neuropathy, CNS signs and symptoms have been found in some
      patients. Recessive mutations in GJC2, the gene for Cx47, are one cause of
      Pelizaeus-Merzbacher-like disease (PMLD), which is characterized by nystagmus
      within the first 6 months of life, cerebellar ataxia by 4 years, and spasticity
      by 6 years of age. MRI imaging shows abnormal myelination. A different recessive
      GJC2 mutation causes a form of hereditary spastic paraparesis, which is a milder
      phenotype than PMLD. Dominant mutations in GJA1, the gene for Cx43, cause
      oculodentodigital dysplasia (ODDD), a pleitropic disorder characterized by oculo
      facial abnormalities including micropthalmia, microcornia and hypoplastic nares,
      syndactyly of the fourth to fifth fingers and dental abnormalities. Neurologic
      manifestations, including spasticity and gait difficulties, are often but not
      universally seen. Recessive GJA1 mutations cause Hallermann-Streiff syndrome, a
      disorder showing substantial overlap with ODDD. This article is part of a Special
      Issue entitled: The Communicating junctions, composition, structure and
      functions.

PMID- 21871439
TI  - Crystal structure of the armadillo repeat domain of adenomatous polyposis coli
      which reveals its inherent flexibility.
AB  - The conserved armadillo repeat (ARM) domain of adenomatous polyposis coli (APC)
      protein plays an important role in the recognition of its binding partners. In
      this study, we report the crystal structure of APC-ARM (residues 407-775), which
      was determined to 2.9 A resolution. Our structure shows that the seven armadillo
      repeats of APC-ARM fold together into a compact domain, with Arm2 and Arm5
      presenting some deviations from canonical armadillo repeats. There is a
      positively charged groove on the surface of APC-ARM, which might be the
      recognition site for APC-binding partners. Comparison of this structure with our
      previously reported structure of APC (407-751), together with normal mode
      analysis, reveals that the APC-ARM domain possesses a limited intrinsic
      flexibility. We propose that this intrinsic flexibility might be an inherent
      property of ARM domains in general.

PMID- 21871440
TI  - Human aryl-hydrocarbon receptor and its interaction with dioxin and physiological
      ligands investigated by molecular modelling and docking simulations.
AB  - Molecular structure of the ligand binding domain of hAhR has been modelled by
      homology modelling techniques and used for docking simulations with dioxin and
      nine more xenobiotics and endogenous ligands. The study evidences that different
      sites may bind these ligands, whereas only one binding site has been previously
      indicated by past studies on the mouse homologous receptor. The differences in
      the sequence of mouse and human AhR ligand binding domain may explain this
      observation, being most of them in the additional sites observed. Preferences of
      the evaluated ligands for the different sites are reported and discussed in view
      of their functional role.

PMID- 21871441
TI  - Detection of phosphorylated mitogen-activated protein kinase in the developing
      spinal cord of the mouse embryo.
AB  - Global understanding of the proteome is a major research topic. The comprehensive
      visualization of the distribution of proteins in vivo or the construction of in
      situ protein atlases may be a valuable strategy for proteomic researchers.
      Information about the distribution of various proteins under physiological and
      pathological conditions should be extremely valuable for the basic and clinical
      sciences. The mitogen-activated protein kinase (MAPK) cascade plays an essential
      role in intracellular signaling in organisms. This cascade also regulates
      biological processes involving development, differentiation, and proliferation.
      Phosphorylation and dephosphorylation are integral reactions in regulating the
      activity of MAPKs. Changes in the phosphorylation state of MAPKs are rapid and
      reversible; therefore, the localizations of physiologically phosphorylated MAPKs
      in vivo are difficult to accurately detect. Furthermore, phosphorylated MAPKs are
      likely to change phosphorylated states through commonly used experimental
      manipulations. In the present study, as a step toward the construction of in situ
      phosphoprotein atlases, we attempted to detect physiologically phosphorylated
      MAPKs in vivo in developing spinal cords of mice. We previously reported an
      improved immunohistochemical method for detecting unstable phosphorylated MAPKs.
      The distribution patterns of phosphorylated MAPKs in the spinal cords of
      embryonic mice from embryonic day 13 (E13) to E17 were observed with an improved
      immunohistochemical method. Phosphorylated extracellular signal-regulated kinase
      1/2 (p-ERK1/2) and phosphorylated c-Jun N-terminal kinase 1/2 (p-JNK1/2) were
      strongly observed in the marginal layer and the dorsal horn from E13 to E17. Our
      results suggest that p-ERK1/2 and p-JNK1/2 play critical roles in the developing
      spinal cord. Constructing phosphoprotein atlases will be possible in the future
      if this work is systematically developed on a larger scale than we presented
      here.

PMID- 21871442
TI  - Characterization of the AT180 epitope of phosphorylated Tau protein by a combined
      nuclear magnetic resonance and fluorescence spectroscopy approach.
AB  - We present here the characterization of the epitope recognized by the AT180
      monoclonal antibody currently used to define an Alzheimer's disease (AD)-related
      pathological form of the phosphorylated Tau protein. Some ambiguity remains as to
      the exact phospho-residue(s) recognized by this monoclonal: pThr231 or both
      pThr231 and pSer235. To answer this question, we have used a combination of
      nuclear magnetic resonance (NMR) and fluorescence spectroscopy to characterize in
      a qualitative and quantitative manner the phospho-residue(s) essential for the
      epitope recognition. Data from the first step of NMR experiments are used to map
      the residues bound by the antibodies, which were found to be limited to a few
      residues. A fluorophore is then chemically attached to a cystein residue
      introduced close-by the mapped epitope, at arginine 221, by mutagenesis of the
      recombinant protein. The second step of Forster resonance energy transfer (FRET)
      between the AT180 antibody tryptophanes and the phospho-Tau protein fluorophore
      allows to calculate a dissociation constant Kd of 30 nM. We show that the sole
      pThr231 is necessary for the AT180 recognition of phospho-Tau and that
      phosphorylation of Ser235 does not interfere with the binding.

PMID- 21871443
TI  - Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated
      reactive oxygen species and mitochondrial membrane depolarization.
AB  - The anticancer activity of salinomycin has evoked excitement due to its recent
      identification as a selective inhibitor of breast cancer stem cells (CSCs) and
      its ability to reduce tumor growth and metastasis in vivo. In prostate cancer,
      similar to other cancer types, CSCs and/or progenitor cancer cells are believed
      to drive tumor recurrence and tumor growth. Thus salinomycin can potentially
      interfere with the end-stage progression of hormone-indifferent and chemotherapy
      resistant prostate cancer. Androgen-responsive (LNCaP) and androgen-refractive
      (PC-3, DU-145) human prostate cancer cells showed dose- and time-dependent
      reduced viability upon salinomycin treatment; non-malignant RWPE-1 prostate cells
      were relatively less sensitive to drug-induced lethality. Salinomycin triggered
      apoptosis of PC-3 cells by elevating the intracellular ROS level, which was
      accompanied by decreased mitochondrial membrane potential, translocation of Bax
      protein to mitochondria, cytochrome c release to the cytoplasm, activation of the
      caspase-3 and cleavage of PARP-1, a caspase-3 substrate. Expression of the
      survival protein Bcl-2 declined. Pretreatment of PC-3 cells with the antioxidant
      N-acetylcysteine prevented escalation of oxidative stress, dissipation of the
      membrane polarity of mitochondria and changes in downstream molecular events.
      These results are the first to link elevated oxidative stress and mitochondrial
      membrane depolarization to salinomycin-mediated apoptosis of prostate cancer
      cells.

PMID- 21871444
TI  - The higher barrier of darunavir and tipranavir resistance for HIV-1 protease.
AB  - Darunavir and tipranavir are two inhibitors that are active against multi-drug
      resistant (MDR) HIV-1 protease variants. In this study, the invitro inhibitory
      efficacy was tested against a MDR HIV-1 protease variant, MDR 769 82T, containing
      the drug resistance mutations of 46L/54V/82T/84V/90M. Crystallographic and
      enzymatic studies were performed to examine the mechanism of resistance and the
      relative maintenance of potency. The key findings are as follows: (i) The MDR
      protease exhibits decreased susceptibility to all nine HIV-1 protease inhibitors
      approved by the US Food and Drug Administration (FDA), among which darunavir and
      tipranavir are the most potent; (ii) the threonine 82 mutation on the protease
      greatly enhances drug resistance by altering the hydrophobicity of the binding
      pocket; (iii) darunavir or tipranavir binding facilitates closure of the wide
      open flaps of the MDR protease; and (iv) the remaining potency of tipranavir may
      be preserved by stabilizing the flaps in the inhibitor-protease complex while
      darunavir maintains its potency by preserving protein main chain hydrogen bonds
      with the flexible P2 group. These results could provide new insights into drug
      design strategies to overcome multi-drug resistance of HIV-1 protease variants.

PMID- 21871445
TI  - Decreased expression of ATP6V1H in type 2 diabetes: a pilot report on the
      diabetes risk study in Mexican Americans.
AB  - OBJECTIVE: Previous studies in mice and humans observed down-regulation of the
      gene expression of ATP6V1H associated with type 2 diabetes. This study identified
      prospectively changes in ATP6V1H expression before and after overt diabetes.
      METHODS: Expression of ATP6V1H in peripheral blood was compared pre and post
      development of diabetes in nine individuals. RESULTS: Considerable variation of
      ATP6V1H mRNA levels was observed between different individuals. However, within
      each individual the decrease in expression of ATP6V1H with the development of
      diabetes was highly statistically significant. CONCLUSIONS: ATP6V1H may represent
      a critical molecular mechanism involved in the development of type 2 diabetes and
      its compilations through its important regulatory effect on vacuolar-ATPase
      activity.

PMID- 21871446
TI  - Insulin rapidly stimulates L-arginine transport in human aortic endothelial cells
      via Akt.
AB  - Insulin stimulates endothelial NO synthesis, at least in part mediated by
      phosphorylation and activation of endothelial NO synthase at Ser1177 and Ser615
      by Akt. We have previously demonstrated that insulin-stimulated NO synthesis is
      inhibited under high culture glucose conditions, without altering Ca(2+)
      stimulated NO synthesis or insulin-stimulated phosphorylation of eNOS. This
      indicates that stimulation of endothelial NO synthase phosphorylation may be
      required, yet not sufficient, for insulin-stimulated nitric oxide synthesis. In
      the current study we investigated the role of supply of the eNOS substrate, L
      arginine as a candidate parallel mechanism underlying insulin-stimulated NO
      synthesis in cultured human aortic endothelial cells. Insulin rapidly stimulated
      L-arginine transport, an effect abrogated by incubation with inhibitors of
      phosphatidylinositol-3'-kinase or infection with adenoviruses expressing a
      dominant negative mutant Akt. Furthermore, supplementation of endothelial cells
      with extracellular L-arginine enhanced insulin-stimulated NO synthesis, an effect
      reversed by co-incubation with the L-arginine transport inhibitor, L-lysine.
      Basal L-arginine transport was significantly increased under high glucose culture
      conditions, yet insulin-stimulated L-arginine transport remained unaltered. The
      increase in L-arginine transport elicited by high glucose was independent of the
      expression of the cationic amino acid transporters, hCAT1 and hCAT2 and not
      associated with any changes in the activity of ERK1/2, Akt or protein kinase C
      (PKC). We propose that rapid stimulation of L-arginine transport contributes to
      insulin-stimulated NO synthesis in human endothelial cells, yet attenuation of
      this is unlikely to underlie the inhibition of insulin-stimulated NO synthesis
      under high glucose conditions.

PMID- 21871447
TI  - Singlet oxygen is essential for neutrophil extracellular trap formation.
AB  - Neutrophil extracellular traps (NETs) that bind invading microbes are pivotal for
      innate host defense. There is a growing body of evidence for the significance of
      NETs in the pathogenesis of infectious and inflammatory diseases, but the
      mechanism of NET formation remains unclear. Previous observation in neutrophils
      of chronic granulomatous disease (CGD) patients, which defect NADPH oxidase (Nox)
      and fail to produce reactive oxygen species (ROS), revealed that ROS contributed
      to the formation of NETs. However, the active species were not identified. In
      this study, we discovered that singlet oxygen, one of the ROS, mediated Nox
      dependent NET formation upon stimulation with phorbol myristate acetate. We also
      revealed that singlet oxygen itself could induce NET formation by a distinct
      system generating singlet oxygen with porfimer sodium (Photofrin) in CGD
      neutrophils, as well as healthy neutrophils. This was independent of Nox
      activation. These results show that singlet oxygen is essential for NET
      formation, and provide novel insights into the pathogenesis of infectious and
      inflammatory diseases.

PMID- 21871449
TI  - Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal
      cells.
AB  - Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their
      cellular microenvironment is essential to maintain 'stemness'. In cancer biology,
      focal adhesion (FA) proteins are involved in survival signal transduction in a
      wide variety of human tumours. To define the role of FA proteins in the
      haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive
      mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y(397)],
      and HSP90alpha/beta and p130CAS, and analysed for reactivity, intensity and
      cellular localisation. Immunofluorescence microscopy allowed us to identify
      qualitative and quantitative differences, and subcellular localisation analysis
      revealed that in pathological MSCs, paxillin, pFAK [Y(397)], and HSP90alpha/beta
      formed nuclear molecular complexes. Increased expression of paxillin, pFAK
      [Y(397)], and HSP90alpha/beta and enhanced nuclear co-localisation of these
      proteins correlated with a consistent proliferative advantage in MSCs from
      patients with refractory anaemia with excess blasts (RAEB) and negatively
      impacted clonogenicity of HPCs. These results suggest that signalling via FA
      proteins could be implicated in HPC-MSC interactions. Further, because FAK is an
      HSP90alpha/beta client protein, these results suggest the utility of
      HSP90alpha/beta inhibition as a target for adjuvant therapy for myelodysplasia.

PMID- 21871448
TI  - Wt1a, Foxc1a, and the Notch mediator Rbpj physically interact and regulate the
      formation of podocytes in zebrafish.
AB  - Podocytes help form the glomerular blood filtration barrier in the kidney and
      their injury or loss leads to renal disease. The Wilms' tumor suppressor-1 (Wt1)
      and the FoxC1/2 transcription factors, as well as Notch signaling, have been
      implicated as important regulators of podocyte fate. It is not known whether
      these factors work in parallel or sequentially on different gene targets, or as
      higher-order transcriptional complexes on common genes. Here, we use the
      zebrafish to demonstrate that embryos treated with morpholinos against wt1a,
      foxc1a, or the Notch transcriptional mediator rbpj develop fewer podocytes, as
      determined by wt1b, hey1 and nephrin expression, while embryos deficient in any
      two of these factors completely lack podocytes. From GST-pull-downs and co
      immunoprecipitation experiments we show that Wt1a, Foxc1a, and Rbpj can
      physically interact with each other, whereas only Rbpj binds to the Notch
      intracellular domain (NICD). In transactivation assays, combinations of Wt1,
      FoxC1/2, and NICD synergistically induce the Hey1 promoter, and have additive or
      repressive effects on the Podocalyxin promoter, depending on dosage. Taken
      together, these data suggest that Wt1, FoxC1/2, and Notch signaling converge on
      common target genes where they physically interact to regulate a podocyte
      specific gene program. These findings further our understanding of the
      transcriptional circuitry responsible for podocyte formation and differentiation
      during kidney development.

PMID- 21871450
TI  - Lamin A, farnesylation and aging.
AB  - Lamin A is a component of the nuclear envelope that is synthesized as a precursor
      prelamin A molecule and then processed into mature lamin A through sequential
      steps of posttranslational modifications and proteolytic cleavages. Remarkably,
      over 400 distinct point mutations have been so far identified throughout the LMNA
      gene, which result in the development of at least ten distinct human disorders,
      collectively known as laminopathies, among which is the premature aging disease
      Hutchinson-Gilford progeria syndrome (HGPS). The majority of HGPS cases are
      associated with a single point mutation in the LMNA gene that causes the
      production of a permanently farnesylated mutant lamin A protein termed progerin.
      The mechanism by which progerin leads to premature aging and the classical HGPS
      disease phenotype as well as the relationship between this disorder and the onset
      of analogous symptoms during the lifespan of a normal individual are not well
      understood. Yet, recent studies have provided critical insights on the cellular
      processes that are affected by accumulation of progerin and have suggested that
      cellular alterations in the lamin A processing pathway leading to the
      accumulation of farnesylated prelamin A intermediates may play a role in the
      aging process in the general population. In this review we provide a short
      background on lamin A and its maturation pathway and discuss the current
      knowledge of how progerin or alterations in the prelamin A processing pathway are
      thought to influence cell function and contribute to human aging.

PMID- 21871451
TI  - Human STEAP3 maintains tumor growth under hypoferric condition.
AB  - Iron is essential in cellular proliferation and survival based on its crucial
      roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients
      with low serum iron, although their actual mechanisms are not well known. To
      elucidate molecular mechanisms of efficient tumor progression under the
      hypoferric condition, we studied the roles of six-transmembrane epithelial
      antigen of the prostate family member 3 (STEAP3), which was reported to
      facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human
      STEAP3-overexpressing cells were established. The impact of STEAP3 expression was
      analyzed about the amount of iron storage, the survival under hypoferric
      conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression
      increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji
      cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced
      apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even
      in hypoferric mice, while parental Raji cells grew less rapidly. In addition,
      iron deficiency enhanced STEAP3 mRNA expression in tumor cells. Furthermore,
      human colorectal cancer tissues exhibited more STEAP3 mRNA expression and iron
      storage compared with normal colon mucosa. These findings indicate that STEAP3
      maintains iron storage in human malignant cells and tumor proliferation under the
      hypoferric condition.

PMID- 21871453
TI  - Plant extract: a natural immune booster for ulcerative colitis.

PMID- 21871452
TI  - Molecular genetics in glaucoma.
AB  - Glaucoma is a family of diseases whose pathology is defined by the progressive
      loss of retinal ganglion cells. Clinically, glaucoma presents as a distinctive
      optic neuropathy with associated visual field loss. Primary open-angle glaucoma
      (POAG), chronic angle-closure glaucoma (ACG), and exfoliation glaucoma (XFG) are
      the most prevalent forms of glaucoma globally and are the most common causes of
      glaucoma-related blindness worldwide. A host of genetic and environmental factors
      contribute to glaucoma phenotypes. This review examines the current status of
      genetic investigations of POAG, ACG, XFG, including the less common forms of
      glaucoma primary congenital glaucoma (PCG), the developmental glaucomas, and
      pigment dispersion glaucoma.

PMID- 21871454
TI  - Chelation therapy for secondary iron overload: is the primary effect less iron or
      less liver fibrosis?

PMID- 21871455
TI  - A rare cause of dysphagia in an adult patient. Diagnosis: Congenital fourth
      branchial arch cyst.

PMID- 21871456
TI  - A large intra-abdominal cystic mass arising from the mesocolon. Diagnosis:
      Mucinous cystadenoma of the mesocolon with high-grade dysplasia.

PMID- 21871457
TI  - Pancreatic stress and regeneration.

PMID- 21871459
TI  - Effects of DPP-4 inhibition on cardiac metabolism and function in mice.
AB  - Type 2 diabetes is associated with an increased risk of cardiac complications.
      Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of
      patients with type 2 diabetes. The effect of DPP-4 inhibitors on myocardial
      metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3weeks of
      treatment with sitagliptin had no effect on body weight and glucose tolerance nor
      on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl
      CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the
      left ventricular myocardium. However, in 10week old db/db-/- mice, a model of
      diabetes and obesity, sitagliptin potently reduced plasma glucose rise in
      peritoneal glucose tolerance tests and reduced weight increase. The myocardium of
      untreated db/db-/- mice exhibited a marked increase of the phosphorylation of
      AMPK, ACC, TSC2, expression of p53 and fatty acid translocase (FAT/CD36) membrane
      expression. These changes were reduced by DPP-4 inhibition. Sitagliptin showed no
      effect on cardiomyocyte size but prevented myocardial fibrosis in the 10week old
      db/db-/- mice and reduced expression of TGF-beta1, markers of oxidative stress
      and the accumulation of advanced glycation end products in cardiomyocytes.
      Working heart analyses did not show an effect of sitagliptin on parameters of
      systolic cardiac function. In animals with diabetes and obesity, sitagliptin
      improved glucose tolerance, reduced weight gain, myocardial fibrosis and
      oxidative stress. Furthermore the study provides evidence that treatment with
      sitagliptin decreases elevated myocardial fatty acid uptake and oxidation in the
      diabetic heart. These observations show beneficial myocardial metabolic effect of
      DPP-4 inhibition in this mouse model of diabetes and obesity.

PMID- 21871458
TI  - Recruitment of bone marrow-derived valve interstitial cells is a normal
      homeostatic process.
AB  - Advances in understanding of the maintenance of the cardiac valves during normal
      cardiac function and response to injury have led to several novel findings,
      including that there is contribution of extra-cardiac cells to the major cellular
      population of the valve: the valve interstitial cell (VIC). While suggested to
      occur in human heart studies, we have been able to experimentally demonstrate,
      using a mouse model, that cells of bone marrow hematopoietic stem cell origin
      engraft into the valves and synthesize collagen type I. Based on these initial
      findings, we sought to further characterize this cell population in terms of its
      similarity to VICs and begin to elucidate its contribution to valve homeostasis.
      To accomplish this, chimeric mice whose bone marrow was repopulated with enhanced
      green fluorescent protein (EGFP) expressing total nucleated bone marrow cells
      were used to establish a profile of EGFP(+) valve cells in terms of their
      expression of hematopoietic antigens, progenitor markers, fibroblast- and
      myofibroblast-related molecules, as well as their distribution within the valves.
      Using this profile, we show that normal (non-irradiated, non-transplanted) mice
      have BM-derived cell populations that exhibit identical morphology and phenotype
      to those observed in transplanted mice. Collectively, our findings establish that
      the engraftment of bone marrow-derived cells occurs as part of normal valve
      homeostasis. Further, our efforts demonstrate that the use of myeloablative
      irradiation, which is commonly employed in studies involving bone marrow
      transplantation, does not elicit changes in the bone marrow-derived VIC phenotype
      in recipient mice.

PMID- 21871460
TI  - Structure and substrate recognition of the Staphylococcus aureus protein tyrosine
      phosphatase PtpA.
AB  - Phosphosignaling through pSer/pThr/pTyr is emerging as a common signaling
      mechanism in prokaryotes. The human pathogen Staphylococcus aureus produces two
      low-molecular-weight protein tyrosine phosphatases (PTPs), PtpA and PtpB, with
      unknown functions. To provide the structural context for understanding PtpA
      function and substrate recognition, establish PtpA's structural relations within
      the PTP family, and provide a framework for the design of specific inhibitors, we
      solved the crystal structure of PtpA at 1 A resolution. While PtpA adopts the
      common, conserved PTP fold and shows close overall similarity to eukaryotic PTPs,
      several features in the active site and surface organization are unique and can
      be explored to design selective inhibitors. A peptide bound in the active site
      mimics a phosphotyrosine substrate, affords insight into substrate recognition,
      and provides a testable substrate prediction. Genetic deletion of ptpA or ptpB
      does not affect in vitro growth or cell wall integrity, raising the possibility
      that PtpA and PtpB have specialized functions during infection.

PMID- 21871461
TI  - Crystal structures of an O-like blue form and an anion-free yellow form of
      pharaonis halorhodopsin.
AB  - Halorhodopsin from Natronomonas pharaonis (pHR) was previously crystallized into
      a monoclinic space group C2, and the structure of the chloride-bound purple form
      was determined. Here, we report the crystal structures of two chloride-free forms
      of pHR, that is, an O-like blue form and an M-like yellow form. When the C2
      crystal was soaked in a chloride-free alkaline solution, the protein packing was
      largely altered and the yellow form containing all-trans retinal was generated.
      Upon neutralization, this yellow form was converted into the blue form. From
      structural comparison of the different forms of pHR, it was shown that the
      removal of a chloride ion from the primary binding site (site I), which is
      located between the retinal Schiff base and Thr126, is accompanied by such a
      deformation of helix C that the side chain of Thr126 moves toward helix G,
      leading to a significant shrinkage of site I. A large structural change is also
      induced in the chloride uptake pathway, where a flip motion of the side chain of
      Glu234 is accompanied by large movements of the surrounding aromatic residues.
      Irrespective of different charge distributions at the active site, there was no
      large difference in the structures of the yellow form and the blue form. It is
      shown that the yellow-to-purple transition is initiated by the entrance of one
      water and one HCl to the active site, where the proton and the chloride ion in
      HCl are transferred to the Schiff base and site I, respectively.

PMID- 21871463
TI  - Analysis of a vaccine model with cross-immunity: when can two competing
      infectious strains coexist?
AB  - We analyse here the vaccine model with cross-immunity proposed by Porco and
      Blower [1]. Porco and Blower [1] show that vaccination can shift the competitive
      balance in favour of a strain that, without vaccination, would be out-competed
      and that vaccination can also promote coexistence of different strains, something
      that normally is not expected [2]. Their results have been mainly obtained
      through numerical simulations, so that the conditions under which a shift in
      competitive balance or coexistence occurs have not been fully established. We
      give a rather complete description of its behaviour, at least in terms of
      equilibria. We find the exact conditions under which vaccination may lead to a
      shift in competitive balance and show that, under these conditions, there always
      exist a range of vaccination rates under which a coexistence equilibrium exists.
      We also find that a coexistence equilibrium exists (and is unstable) in a 'bi
      stability' region, where both monomorphic equilibria are stable. This fact has
      been rarely observed in models of competition between pathogen strains.

PMID- 21871462
TI  - A multicellular model for differential regulation of circadian signals in the
      core and shell regions of the suprachiasmatic nucleus.
AB  - We developed a multicellular model of the mammalian circadian clock characterized
      by a high degree of heterogeneity with respect to single cell periodicity and
      behavior (intrinsic and driven oscillators), neurotransmitter release (VIP, GABA
      and glutamate synthesis) and spatial organization (core and shell regions),
      mimicking structural patterns within the suprachiasmatic nucleus (SCN) associated
      with distinct circadian functions. We simulated the SCN core and shell separately
      utilizing experimentally derived connectivity schemes for the two subdivisions as
      observed within the rat SCN. The core was modeled via a small world network
      characterized by VIP and GABA co-localization, whereas the shell was simulated as
      a nearest neighbor network promoting local GABAergic connections. To study the
      function of the axonal plexus extending from the densely innervated ventrolateral
      region to distal areas across the dorsomedial SCN, directed long range links from
      the core to the shell were gradually introduced via a probability p(cs) that
      ranged from 0 to 1. A probability value of 0 excluded core-shell interactions,
      whereas p(cs)=1 achieved maximal connectivity between the two regions. Our model
      exhibited a threshold in the number of core-to-shell links required for
      sufficient cell-to-cell coordination to maintain periodicity and rhythmic
      behavior across the entire model network (including both shell and core
      populations) in constant darkness as well as 12:12h light-dark cycles. By
      contrast, constant light was shown to increase phase synchronization across the
      shell while core populations remained poorly synchronized, suggesting
      differential light response across the two SCN compartments. We further simulated
      increasing percentages of intrinsic oscillators and demonstrated a negative
      correlation between the number of intrinsic oscillators distributed across the
      SCN and the ability of the system to produce synchronized signals. Simulations
      that differed with respect to the placement of intrinsic oscillators supported
      the hypothesis that improved synchronization is achieved with networks
      characterized by localized intrinsic oscillators placed exclusively within the
      shell versus networks containing uniformly distributed intrinsic oscillators in
      both SCN compartments. This study has successfully reproduced a number of
      spatiotemporal and behavioral attributes of the SCN, providing a useful
      computational tool to correlate observed circadian phenotypes with distinct
      chemoarchitectural properties of spatially localized neural populations.

PMID- 21871464
TI  - Effects of the Valsalva maneuver on pial artery pulsation and subarachnoid width
      in healthy adults.
AB  - AIM: The objective was to characterize the effects of Valsalva maneuver (VM) on
      the amplitude of cerebrovascular pulsation (CVP), and to explore the direct
      interactions between the cerebral vasculature and the cerebrospinal fluid
      compartment in VMIII. METHODS: Twenty-nine healthy volunteers between the ages of
      25 and 40 (29.3 +/- SE 4.0) were studied. Changes in the amplitude of CVP (cc-TQ)
      and width of subarachnoid space (SAS; sas-TQ) were recorded with NIR-T/BSS
      sensor. Changes in arterial blood pressure (ABP) and heart rate were measured
      using Finapres. Cerebral blood flow velocity (CBFV) in the left middle cerebral
      artery was recorded with transcranial doppler. RESULTS: sas-TQ remained
      unchanged, while cc-TQ increased in VMI (+40% vs. baseline). In VMIIa, sas-TQ
      increase (+3.4% vs. baseline) and deep decrease in cc-TQ (-81% vs. baseline) were
      observed. sas-TQ decrease started in VMIIb (-2.7% vs. baseline), with
      simultaneous slight increase in cc-TQ (-58% vs. baseline). In VMIII deep sas-TQ
      decrease (-6.2% vs. baseline) was associated with huge increase in cc-TQ (+110%
      vs. baseline; r=-0.56, p<0.01). During VMIV sas-TQ increased (-4.8% vs. baseline)
      while cc-TQ decreased (+38% vs. baseline). The drop of cc-TQ in VMIIa was
      significantly greater than corresponding changes in CBFV and ABP. Increase in cc
      TQ in VMIII preceded CBFV and ABP changes in VMIV. CONCLUSION: The VM evokes
      significant changes in the amplitude of CVP. Changes in small vessel pulsation
      precede changes in CBFV. There are direct interactions between cc-TQ and sas-TQ
      in VMIII. NIR-T/BSS allows for continuous, non-invasive monitoring of the
      amplitude of CVP and width of the SAS.

PMID- 21871465
TI  - Modulation of fear/anxiety responses, but not food intake, following alpha
      adrenoceptor agonist microinjections in the nucleus accumbens shell of free
      feeding rats.
AB  - This study investigated the effect of alpha-adrenoceptor agonists microinjected
      into the shell region of the accumbens nucleus (AcbSh) on feeding and anxiety
      related behaviors in free-feeding rats. Male Wistar rats with a chronically
      implanted cannula into the AcbSh were unilaterally microinjected with either
      clonidine (CLON, alpha(2)-adrenoceptor agonist) or phenylephrine (PHEN, alpha(1)
      adrenoceptor agonist) at the doses of 6 and 20 nmol and submitted to the elevated
      plus-maze (EPM), a pre-clinical test of anxiety. Immediately after the EPM test,
      the animals underwent food intake evaluation for 30 min. The data showed that
      rats microinjected with CLON (20 nmol/0.2 MUl) into the AcbSh exhibited increased
      %Open arm time, which is compatible with an anxiolytic-like effect. The CLON
      induced anxiolysis was corroborated by increased head-dipping and decreased
      stretched-attend posture, two ethologically derived behaviors which are
      fear/anxiety-motivated. The animal's locomotor activity was not changed by 20
      nmol CLON microinjection into the AcbSh. However, neither dose of PHEN
      microinjected into the AcbSh was able to alter either the spatial-temporal or
      ethological variables representative of fear/anxiety and locomotion. Food intake
      was not altered by any dose of CLON and PHEN microinjected into the AcbSh, but
      the 20 nmol CLON microinjection induced increased motor activity in the feeding
      test. The data suggests that noradrenergic projections to the AcbSh may underlie
      fear/anxiety modulation through alpha(2)-adrenoceptor in the AcbSh, while feeding
      behavior was unaffected by noradrenergic modulation in the AcbSh of free-feeding
      rats. This article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21871466
TI  - Circadian rhythms and depression: human psychopathology and animal models.
AB  - Most organisms (including humans) developed daily rhythms in almost every aspect
      of their body. It is not surprising that rhythms are also related to affect in
      health and disease. In the present review we present data that demonstrate the
      evidence for significant interactions between circadian rhythms and affect from
      both human studies and animal models research. A number of lines of evidence
      obtained from human and from animal models research clearly demonstrate
      relationships between depression and circadian rhythms including (1) daily
      patterns of depression; (2) seasonal affective disorder; (3) connections between
      circadian clock genes and depression; (4) relationship between sleep disorders
      and depression; (5) the antidepressant effect of sleep deprivation; (6) the
      antidepressant effect of bright light exposure; and (7) the effects of
      antidepressant drugs on sleep and circadian rhythms. The integration of data
      suggests that the relationships between the circadian system and depression are
      well established but the underlying biology of the interactions is far from being
      understood. We suggest that an important factor hindering research into the
      underlying mechanisms is the lack of good animal models and we propose that
      additional efforts in that area should be made. One step in that direction could
      be the attempt to develop models utilizing diurnal animals which might have a
      better homology to humans with regard to their circadian rhythms. This article is
      part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21871467
TI  - Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats:
      social versus non-social effects.
AB  - Recent studies demonstrated potent behavioral effects of centrally applied
      neuropeptide S (NPS) in mice and rats. These include increased arousal and
      wakefulness, facilitation of fear extinction and object memory consolidation and
      anxiolysis. Here, we compared the effects of NPS on both social and non-social
      memory, in male rats, and on social preference/social anxiety versus non-social
      anxiety after either intracerebroventricular (icv) or nasal application.
      Intranasal application of neuropeptides has been successfully employed to alter
      behavioral parameters in humans and rodents, but studies concerning nasal
      application of NPS are lacking so far. First, we confirmed the facilitatory
      effect of icv NPS (1 nmol) on object discrimination after an inter-exposure
      interval (IEI) of 240 min. These effects were context-dependent, as icv NPS (1
      nmol) did not prolong social memory in a social discrimination paradigm. Second,
      we confirmed the anxiolytic effect of icv NPS (1 nmol) on the elevated plus-maze,
      whereas neither icv NPS (1 nmol) nor NPS receptor antagonist (10 nmol) altered
      social preference/social avoidance behavior. Third, nasal NPS (4-40 nmol applied
      topically on the rhinarium) facilitated object discrimination in a dose-dependent
      manner. Also, the anxiolytic effect of NPS on the elevated plus-maze could be
      confirmed after nasal administration (40 nmol). In contrast, identical doses of
      subcutaneously injected NPS failed to produce corresponding behavioral effects in
      both tests. Our findings provide evidence for memory-enhancing and anxiolytic
      effects of icv NPS in a non-social context. We could further show that these
      effects are context-specific, as social memory and social preference behavior
      remained unchanged after icv NPS. The effects of icv NPS were replicated by nasal
      application of the neuropeptide. Thus, nasal application of NPS seems to be a
      useful method in rodents for screening for behavioral or physiological effects
      before more specific and time-consuming, intracerebral methods are employed, and
      may represent a viable therapeutic approach for NPS treatment of patients with
      psychiatric illnesses such as anxiety or panic disorders. This article is part of
      a Special Issue entitled 'Anxiety and Depression'.

PMID- 21871468
TI  - The effect of central (macula) sparing on contralateral line bisection bias: a
      study with virtual hemianopia.
AB  - Hemianopic patients show a contralesional bisection bias, but it is unclear
      whether this is a consequence of their field loss or related to extrastriate
      damage. One observation cited against the former is that hemianopic bisection
      bias does not vary with the degree of central (macular) sparing; however, it is
      unclear to what extent central sparing should affect this bias. Our goal was to
      determine the effect of central sparing on line bisection biases from field loss
      alone, with two approaches. First, we studied 12 healthy subjects viewing lines
      under conditions of virtual hemianopia, created by a gaze-contingent technique.
      Second, we calculated the effect predicted by a visuospatial model of the effect
      of central magnification on line representations in the visual system. Our
      results first replicated the contralateral line bisection bias with hemianopia,
      confirming that this can be generated by visual hemifield loss in the absence of
      extrastriate damage. Central sparing had only a modest effect on hemianopic
      bisection bias, with only slightly less bias with 10 degrees  compared to 2
      degrees  of central sparing. In accordance with these empiric data, computing the
      center of mass for line representations in our model showed only a shallow
      decline in bisection bias as central sparing increased from 0 to 10 degrees . We
      conclude that contralateral bisection bias only decreases slightly with central
      sparing, and that the absence of a statistically significant effect of central
      sparing in patients cannot be taken as evidence against a visual origin of
      contralateral hemianopic line bisection bias.

PMID- 21871469
TI  - Selective modulations of attentional asymmetries after sleep deprivation.
AB  - Pseudoneglect is a slight but consistent misplacement of attention toward the
      left visual field, commonly observed in young healthy subjects. This leftward
      attentional bias is thought to result from a right hemispheric dominance in
      visuospatial processing. Changes in endogenous levels of alertness may modulate
      attentional asymmetries and pseudoneglect in particular. In line with this
      hypothesis, it has been shown that sleep deprived shift-workers present a
      reversal of their attentional bias in a landmark (LDM) task (Manly, T., Dobler,
      V. B., Dodds, C. M., & George, M. A. (2005). Rightward shift in spatial awareness
      with declining alertness. Neuropsychologia, 43(12), 1721-1728). However,
      circadian disturbances and fatigue effects at the end of a shift work may have
      contributed to this reversal effect. In a first experiment, we show that sleep
      deprivation (SD) under controlled conditions does not markedly change the
      leftward bias, observable both at 21:00 and at 07:00 after SD. In a second
      experiment, we tested the hypothesis that a drastic reduction or inversion in the
      attentional bias would be present only when both the circadian drive for sleep
      propensity is maximal (i.e. around 05:00) and homeostatic sleep pressure is high.
      Thus participants were tested at 21:00 and under SD conditions at 05:00 and
      09:00. Additionally, we used the greyscales (GS) task well-known to evidence a
      leftward bias in luminance judgments. Although results evidenced a consistent
      leftward bias both in the LDM and GS, we found a suppression of the leftward bias
      at the circadian nadir of alertness (05:00) after SD only for the GS, but not for
      the LDM. Noticeably, the leftward bias in the GS vanished at 05:00 after SD but
      reappeared at 09:00 despite continued SD, suggesting a predominant circadian
      influence on attentional asymmetries in the GS. Additionally, inter-sessions
      correlations evidenced a reproducible, consistent bias both in the LDM and GS,
      with no consistent relationship between the two tasks, suggesting independence of
      the neural networks subtending performance in LDM and GS. Overall, our results
      suggest that SD per se does not impede the leftward bias both in LDM and GS,
      whereas circadian-related variations in vigilance may impact attentional
      asymmetries in luminance judgments.

PMID- 21871470
TI  - Yolk testosterone levels and offspring phenotype correlate with parental age in a
      precocial bird.
AB  - Parents, and particularly mothers, can influence their offspring's development in
      non-genetic ways. Maternal effects can occur during the mothering phase as well
      as during the embryonic phase. Prenatal maternal effects in birds can be mediated
      by yolk steroid hormones that influence subsequent offspring development. Studies
      have focused mainly on the influence of laying females' living conditions on yolk
      hormonal contents, and rarely on the effects of individual characteristics. Here,
      we investigated prenatal influence of parent age on yolk steroid levels and on
      offspring phenotype. We compared Japanese quail at two different ages: at the
      beginning of their reproductive cycle (11 weeks old: age 1) and six months later,
      after egg production peak (37 weeks old: age 2). Egg composition, reproductive
      outcomes, and offspring growth, sexual development and behaviour were studied at
      both ages. We found that laying rate, fertility and chick survival rates declined
      between age 1 and age 2. Age 2 eggs had relatively lighter shells and higher yolk
      plus albumen contents; they also had lower testosterone contents. Age 2 offspring
      weighed more at hatching than did age 1 offspring; subsequently their growth
      patterns differed and their sexual development was more precocious. Age 2
      offspring were less emotional than age 1 offspring when encountering a novel
      environment, and they appeared more sensitive to social separation. Our study
      shows, for the first time in a bird species, a strong impact of parental age on
      offspring phenotype, and especially on behaviour, an impact that is possibly
      mediated via modulation of yolk testosterone content.

PMID- 21871471
TI  - Multiple exposures to familiar conspecific withdrawal is a novel robust stress
      paradigm in ewes.
AB  - Paradigms used so far to study the effects of social isolation in sheep confound
      the effects of social isolation with those of other stressors (e.g. new
      environment) and showed contradictory effects after multiple social isolations.
      We propose here to characterize and examine the repeatable effects of social
      isolation induced by the familiar conspecific withdrawal (FCW). This latter test
      consists of socially isolating the ewe by the removal of group mates from the
      room test for 3 h. Behavioral and endocrine responses of adult ovariectomized
      estradiol implanted ewes were compared 90 min before and 90 min after FCW, which
      was applied three times every fourteen days. We observed that each FCW induced
      significant increases in plasma cortisol level, in the number of vocalizations,
      foot pawing, circling attempts and a significant decrease in time spent lying
      down. An increase in plasma cortisol levels and decrease in duration of
      maintenance behaviors were significantly lower after the third FCW than after the
      first one. These differences could be explained by higher plasma cortisol levels
      and lower duration of maintenance behaviors before the third FCW than before the
      first FCW suggesting an anticipation of the social isolation period. These data
      indicate that social isolation is sufficient to induce distress with stable
      stressful responses after multiple exposures to familiar conspecific withdrawal.

PMID- 21871472
TI  - Roles of dorsomedial hypothalamic cholecystokinin signaling in the controls of
      meal patterns and glucose homeostasis.
AB  - A role for dorsomedial hypothalamus (DMH) cholecystokinin (CCK) signaling in
      feeding control has been proposed. Administration of CCK into the DMH reduces
      food intake and OLETF rats lacking CCK1 receptors (CCK1R) become hyperphagic and
      obese. We hypothesized that site specific replenishment of CCK1R in the DMH of
      OLETF rats would attenuate aspects of their feeding deficits. Recombinant vectors
      of adeno-associated viral (AAV)-mediated expression of CCK1R (AAVCCK1R) were
      bilaterally delivered into the DMH of OLETF. OLETF rats with AAVCCK1R injections
      demonstrated a 65% replenishment of Cck1r mRNA expression in the DMH relative to
      lean LETO control rats. Although this level of replenishment did not
      significantly affect overall food intake or body weight through 14 weeks
      following viral injections, meal patterns were partially normalized in OLETF rats
      receiving AAVCCK1R with a significant decrease in dark cycle meal size and a
      small but significant decrease in daily food intake in the meal analysis
      chambers. Importantly, the elevation in blood glucose level of OLETF rats was
      attenuated by the AAVCCK1R injections (p=0.03), suggesting a role for DMH CCK
      signaling in glucose homeostasis. In support of this role, administration of CCK
      into the DMH of intact rats enhanced glucose tolerance, as this occurred through
      activation of CCK1R but not CCK2R signaling. In conclusion, partial replenishment
      of CCK1R in the DMH of OLETF rats, although insufficient for altering overall
      food intake and body weight, normalizes meal pattern changes and reduces blood
      glucose levels. Our study also shows a novel role of DMH CCK signaling in glucose
      homeostasis.

PMID- 21871473
TI  - Food anticipatory behaviour as an indicator of stress response and recovery in
      Atlantic salmon post-smolt after exposure to acute temperature fluctuation.
AB  - In this study we evaluated Pavlovian conditioned food anticipatory behaviour as a
      potential indicator for stress in groups of Atlantic salmon, and compared this
      with the physiological stress responses of cortisol excretion into water and
      hyper-consumption of oxygen. We hypothesised that environmental stress would
      result in reduced feeding motivation. To assess this, we measured the strength of
      anticipatory behaviour during a period of flashing light that signalled arrival
      of food. Further, we expected that fish given a reduced food ration would be less
      sensitive to environmental stress than fish fed full ration. The fish responded
      to an acute temperature fluctuation with hyper-consumption of oxygen that
      decreased in line with the temperature, and elevated cortisol excretion up to 1h
      after the stressor. These physiological responses did not differ significantly
      between the food ration groups. The anticipatory behaviour was significantly
      reduced after the stressor and returned to control levels after 1 to 2 h in the
      reduced ration group, but not until after 3 to 4 h in the full ration group. Our
      results show that acute stress can be measured in terms of changes to feeding
      motivation, and that it is a more sensitive indicator of stress that influences
      the fish over a longer time period than measures of change in cortisol excretion.

PMID- 21871474
TI  - Inducible bilirubin oxidase: a novel function for the mouse cytochrome P450 2A5.
AB  - We have previously shown that bilirubin (BR), a breakdown product of haem, is a
      strong inhibitor and a high affinity substrate of the mouse cytochrome P450 2A5
      (CYP2A5). The antioxidant BR, which is cytotoxic at high concentrations, is
      potentially useful in cellular protection against oxygen radicals if its
      intracellular levels can be strictly controlled. The mechanisms that regulate
      cellular BR levels are still obscure. In this paper we provide preliminary
      evidence for a novel function of CYP2A5 as hepatic "BR oxidase". A high
      performance liquid chromatography/electrospray ionisation mass spectrometry
      screening showed that recombinant yeast microsomes expressing the CYP2A5 oxidise
      BR to biliverdin, as the main metabolite, and to three other smaller products
      with m/z values of 301, 315 and 333. The metabolic profile is significantly
      different from that of chemical oxidation of BR. In chemical oxidation the
      smaller products were the main metabolites. This suggests that the enzymatic
      reaction is selective, towards biliverdin production. Bilirubin treatment of
      primary hepatocytes increased the CYP2A5 protein and activity levels with no
      effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a
      protein synthesis inhibitor, resulted in increased half-life of the CYP2A5
      compared to cells treated only with CHX. Collectively, the observations suggest
      that the CYP2A5 is potentially an inducible "BR oxidase" where BR may accelerate
      its own metabolism through stabilization of the CYP2A5 protein. It is possible
      that this metabolic pathway is potentially part of the machinery controlling
      intracellular BR levels in transient oxidative stress situations, in which high
      amounts of BR are produced.

PMID- 21871475
TI  - Vitisin B, a resveratrol tetramer, inhibits migration through inhibition of PDGF
      signaling and enhancement of cell adhesiveness in cultured vascular smooth muscle
      cells.
AB  - Vascular smooth muscle cells (VSMCs) play an important role in normal vessel
      formation and in the development and progression of cardiovascular diseases.
      Grape plants contain resveratrol monomer and oligomers and drinking of wine made
      from grape has been linked to "French Paradox". In this study we evaluated the
      effect of vitisin B, a resveratrol tetramer, on VSMC behaviors. Vitisin B
      inhibited basal and PDGF-induced VSMC migration. Strikingly, it did not inhibit
      VSMC proliferation but inversely enhanced cell cycle progression and
      proliferation. Among the tested resveratrol oligomers, vitisin B showed an
      excellent inhibitory activity and selectivity on PDGF signaling. The anti
      migratory effect by vitisin B was due to direct inhibition on PDGF signaling but
      was independent of interference with PDGF binding to VSMCs. Moreover, the
      enhanced VSMC adhesiveness to matrix contributed to the anti-migratory effect by
      vitisin B. Fluorescence microscopy revealed an enhanced reorganization of actin
      cytoskeleton and redistribution of activated focal adhesion proteins from cytosol
      to the peripheral edge of the cell membrane. This was confirmed by the
      observation that enhanced adhesiveness was repressed by the Src inhibitor.
      Finally, among the effects elicited by vitisin B, only the inhibitory effect
      toward basal migration was partially through estrogen receptor activation. We
      have demonstrated here that a resveratrol tetramer exhibited dual but opposite
      actions on VSMCs, one is to inhibit VSMC migration and the other is to promote
      VSMC proliferation. The anti-migratory effect was through a potent inhibition on
      PDGF signaling and novel enhancement on cell adhesion.

PMID- 21871476
TI  - Visual influence on the slow oscillatory eye movement discovered during a visual
      fixation task.
AB  - A slow oscillatory movement (SOM) has previously been discovered superimposed on
      the three well known components of fixational eye movements. The purpose of the
      present study was to explore the visual influence on the control mechanism of the
      SOM. Three tests with different fixation targets and backgrounds were prepared.
      The eye position during a fixation task on healthy test subjects has been
      recorded by the Chronos eye tracking device. The visual stimuli with no or less
      information triggered larger SOM amplitudes. None of the investigated conditions
      significantly influenced on SOM frequency.

PMID- 21871478
TI  - Repeated pre-exposure to tobacco smoke potentiates subsequent locomotor responses
      to nicotine and tobacco smoke but not amphetamine in adult rats.
AB  - These studies investigated if pre-exposure to tobacco smoke affects the locomotor
      response to tobacco smoke, nicotine, and amphetamine in adult rats. The rats were
      habituated to an open field for 3-4 days and then exposed to tobacco smoke for
      2h/day for 13-14 days. The effect of exposure to tobacco smoke on locomotor
      activity was investigated after 1, 7, and 14 days of smoke exposure and after one
      2-hour exposure session that followed a 3-week off period. The effects of tobacco
      smoke on the locomotor responses to nicotine (0.04 and 0.4 mg/kg, base) and
      amphetamine (0.1 and 0.5mg/kg) were investigated on day 14, one day after the
      last smoke exposure session. The locomotor response to tobacco smoke was
      increased after 7 and 14 days of smoke exposure and after one exposure session
      after the 3-week off-period. The acute administration of the high dose of
      nicotine (0.4 mg/kg) led to a brief period of hypoactivity that was followed by a
      period of hyperactivity. Pre-exposure to tobacco smoke attenuated the nicotine
      induced hypoactivity and potentiated the nicotine-induced hyperactivity. The low
      dose of nicotine (0.04 mg/kg) did not affect locomotor activity in the control
      rats but increased the total distance traveled in the tobacco smoke exposed rats.
      Exposure to tobacco smoke did not affect the locomotor response to amphetamine.
      These findings indicate that exposure to tobacco smoke leads to tolerance to the
      depressant effects of nicotine and potentiates the stimulant effects of nicotine
      and tobacco smoke.

PMID- 21871477
TI  - The molecular physiology of CRH neurons.
AB  - Corticotropin releasing hormone (CRH) is essential for stress adaptation by
      mediating hypothalamic-pituitary-adrenal (HPA) axis, behavioral and autonomic
      responses to stress. Activation of CRH neurons depends on neural afferents from
      the brain stem and limbic system, leading to sequential CRH release and
      synthesis. CRH transcription is required to restore mRNA and peptide levels, but
      termination of the response is essential to prevent pathology associated with
      chronic elevations of CRH and HPA axis activity. Inhibitory feedback mediated by
      glucocorticoids and intracellular production of the repressor, Inducible Cyclic
      AMP Early Repressor (ICER), limit the magnitude and duration of CRH neuronal
      activation. Induction of CRH transcription is mediated by the cyclic AMP/protein
      kinase A/cyclic AMP responsive element binding protein (CREB)-dependent pathways,
      and requires cyclic AMP-dependent nuclear translocation of the CREB co-activator,
      Transducer of Regulated CREB activity (TORC). This article reviews current
      knowledge on the mechanisms regulating CRH neuron activity.

PMID- 21871480
TI  - The effect of two types of sms-texts on the uptake of screening mammogram: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the effect of two different types of short text message
      service (SMS-text) reminders on the uptake of screening mammogram. METHODS: A
      randomized controlled trial was conducted in 2010 among females aged between 40
      and 75, benefiting from the Health Insurance Plan at the American University of
      Beirut, whose cell phone numbers were available in their electronic medical
      records, and who did not do a mammogram in the past 2 years. The sample (n=385)
      was randomly divided into two subgroups. The first subgroup (n1=192) received a
      general SMS-text inviting its members to do a mammogram while the second subgroup
      (n2=193) received an additional informative SMS-text informing them about the
      benefits of mammogram screening. RESULTS: 30.7% (59) of subgroup 1 and 31.6% (61)
      of subgroup 2 underwent a mammogram screening test during the 6 months follow up
      interval post-intervention (Chi-square test, p-value >= 0.05). There was no
      difference between the response rates in the two subgroups. CONCLUSION: A brief
      invitation SMS-text message for screening mammogram was found to be as effective
      as a detailed informative one.

PMID- 21871479
TI  - Modifiable determinants of hearing impairment in adults.
AB  - OBJECTIVE: To identify factors contributing to the declining prevalence of
      hearing impairment in more recent generations. METHODS: We used data on hearing
      thresholds and potential risk factors of hearing impairment collected from
      studies in Beaver Dam, Wisconsin, the Epidemiology of Hearing Loss Study (1993
      1995, n=3753; 1998-2000, n=2800 and 2003-2005, n=2395), the concurrent Beaver Dam
      Eye Study on the same cohort, and a subgroup (n=2173) of the Beaver Dam Offspring
      Study (2005-2008). RESULTS: Educational attainment significantly reduced the odds
      ratio (OR) of the birth cohort effect on hearing impairment from 0.90 to 0.93,
      while a history of ear infection had a reverse effect on the decreasing trend
      (significantly changing the OR from 0.93 to 0.94). Occupational noise exposure,
      smoking, and a history of cardiovascular disease, while associated with hearing
      impairment, did not attenuate the cohort effect. The cohort effect remained
      significant after known risk factors were adjusted (OR=0.93; 95% confidence
      interval, 0.89-0.97). CONCLUSION: These data provide strong evidence that
      environmental, lifestyle, or other modifiable factors contribute to the etiology
      of hearing impairment and add support to the idea that hearing impairment in
      adults may be prevented or delayed.

PMID- 21871481
TI  - Null misinterpretation in statistical testing and its impact on health risk
      assessment.
AB  - Statistical methods play a pivotal role in health risk assessment, but not always
      an enlightened one. Problems well known to academics are frequently overlooked in
      crucial nonacademic venues such as litigation, even though those venues can have
      profound impacts on population health and medical practice. Statisticians have
      focused heavily on how statistical significance overstates evidence against null
      hypotheses, but less on how statistical nonsignificance does not correspond to
      evidence for the null. I thus present an example of a highly credentialed
      statistical expert conflating high "nonsignificance" with strong support for the
      null, via misinterpretation of a P-value as a posterior probability of the null
      hypothesis. Reverse-Bayes analyses reveal that nearly all the support for the
      null claimed by the expert must have come from the expert's prior, rather than
      the data, there being no background data that could support a strong prior. The
      example illustrates how inattention to the actual meaning of P-values and
      confidence limits allow extremely biased prior opinions (including null-spiked
      opinions) to be presented as if they were objective inferences from the data.

PMID- 21871482
TI  - How can irregular causal generalizations guide practice?
AB  - In this essay, I shall be concerned with the sort of "irregular" causal
      generalizations that epidemiologists aim to discover. Examples include "Smoking
      causes lung cancer," "HIV viruses cause AIDs," or "Low dose aspirin prevents
      strokes." What do these claims mean and how should they guide action? I argue
      that philosophers have mistakenly believed that answering these questions calls
      for a theory of what it is for one event to be a probabilistic cause of another.
      But this theory fails to provide plausible truth conditions for irregular causal
      generalizations. Indeed, it implies that most of them are false. I sketch a more
      plausible view, but point out the risks one takes in relying on these
      generalizations to guide action.

PMID- 21871483
TI  - Production of a novel biomacromolecule for nanodevices from glycerol as carbon
      source in different conditions.
AB  - The aim of this study was the investigation of producing cruxrhodopsin as a
      biomacromolecule with nanofunction from glycerol as carbon source using several
      process parameters. The optimum medium composition for cruxrhodopsin production
      was found to contain glycerol 1%, yeast extract 0.05% and K(2)HPO(4) 0.001%. The
      production of cruxrhodopsin in optimal conditions was 139.86 mg/l. In conclusion,
      halophilic microorganism Haloarcula sp. IRU1 could be a potential microorganism
      for production of cruxrhodopsin from glycerol in different conditions.

PMID- 21871484
TI  - Optimization of polysaccharides extraction from Tetrastigma hemsleyanum Diels et
      Gilg using response surface methodology.
AB  - A 15-run Box-Behnken design (BBD) was used to optimize the extraction conditions
      of polysaccharides from Tetrastigma hemsleyanum Diels et Gilg. Three factors such
      as extraction temperature ( degrees C), extraction time (h), and ratio of water
      to raw material were investigated. The experimental data were fitted to a second
      order polynomial equation using multiple regression analysis and also examined
      using the appropriate statistical methods. The adjusted coefficient of
      determination (R(Adj)(2)) for the model was 0.9754, and the probability value
      (P=0.001) demonstrated a high significance for the regression model. The optimum
      extraction conditions were found to be: optimized extraction temperature 83.3
      degrees C, extraction time 1.55 h and ratio of water to raw material 29.48. Under
      these conditions, the mean extraction yield of polysaccharides was 5.182 +/-
      0.093 %, which was in good agreement with the predicted model value.

PMID- 21871485
TI  - Big defensins and mytimacins, new AMP families of the Mediterranean mussel
      Mytilus galloprovincialis.
AB  - Antimicrobial peptides (AMPs) play a fundamental role in the innate immunity of
      invertebrates, preventing the invasion of potential pathogens. Mussels can
      express a surprising abundance of cysteine-rich AMPs pertaining to the defensin,
      myticin, mytilin and mytimycin families, particularly in the circulating
      hemocytes. Based on deep RNA sequencing of Mytilus galloprovincialis, we describe
      the identification, molecular diversity and constitutive expression in different
      tissues of five novel transcripts pertaining to the macin family (named
      mytimacins) and eight novel transcripts pertaining to the big defensins family
      (named MgBDs). The predicted antimicrobial peptides exhibit a N-terminal signal
      peptide, a positive net charge and a high content in cysteines, allegedly
      organized in intra-molecular disulfide bridges. Mytimacins and big defensins
      therefore represent two novel AMP families of M. galloprovincialis which extend
      the repertoire of cysteine-rich AMPs in this bivalve mollusk.

PMID- 21871486
TI  - Exposure to methamidophos at adulthood adversely affects serotonergic biomarkers
      in the mouse brain.
AB  - Epidemiologic studies describe a potential risk of depression and suicide in farm
      workers exposed to organophosphates (OPs). In a previous study we observed an
      increase in depressive-like behavior in adult mice exposed to the OP pesticide
      methamidophos. Considering the association between depression and the
      serotonergic (5HT) system, in the present study we investigated whether a
      subchronic exposure to methamidophos affects the serotonergic system of adult
      mice. From postnatal day 60 to 89 (PN60 to PN89), one of two concentrations of
      methamidophos (higher dose: 5.25 MUg/ml; lower dose: 1.31 MUg/ml) or vehicle was
      administered in the drinking water of male Swiss mice. We evaluated three
      serotonergic biomarkers during (PN89) and after (PN100) the exposure period:
      5HT(1A) receptor binding with [(3)H]OH-DPAT, 5HT(2) receptor binding with
      [(3)H]ketanserin and 5HT transporter binding with [(3)H]paroxetine. Methamidophos
      elicited robust decreases in binding for all 5HT markers. These decreases were
      evident in brain regions containing 5HT cell bodies and dendritic arbors
      (midbrain, brainstem) as well as in the cerebral cortex, which contains 5HT
      projections. In the cerebral cortex, effects were identified in mice exposed to
      the higher dose of methamidophos while in the midbrain and brainstem, both doses
      elicited significant effects. Overall, effects were present both during and after
      exposure, even though there were some regional disparities regarding the
      persistence of effects. Our results indicate that exposure to methamidophos
      affects synaptic transmission promoting decreases of specific serotonergic
      biomarkers. These data suggest a mechanism of action of this pesticide that might
      explain the increased depressive-like behavior in adult mice.

PMID- 21871487
TI  - Haemophilus parainfluenzae prosthetic joint infection. The importance of accurate
      microbiological diagnosis and options for management.

PMID- 21871488
TI  - Optimisation of in ovo electroporation of the chick neural tube.
AB  - Chick in ovo neural tube electroporation has become a widely used method for
      assaying gene function during embryonic development. Since its first description,
      many variants of this technique have been described, with varying values for
      specific parameters such as electrode type and spacing, voltage, pulse duration
      and plasmid DNA concentration. Here we examine the influence of some of these
      variables and derive a detailed and optimal protocol for electroporating the
      caudal neural tube during the third day of embryonic development. Our findings
      highlight the importance of electrode placement and DNA dilution buffer for
      optimal expression and absence of electroporation artifacts.

PMID- 21871489
TI  - A critical note on the definition of phase-amplitude cross-frequency coupling.
AB  - Recent studies have observed the ubiquity of phase-amplitude coupling (PAC)
      phenomenon in human and animal brain recordings. While various methods were
      performed to quantify it, a rigorous analytical definition of PAC is lacking.
      This paper yields an analytical definition and accordingly offers theoretical
      insights into some of the current methods. A direct PAC estimator based on the
      given definition is presented and shown theoretically to be superior to some of
      the previous methods such as general linear model (GLM) estimator. It is also
      shown that the proposed PAC estimator is equivalent to GLM estimator when a
      constant term is removed from its formulation. The validity of the derivations is
      demonstrated with simulated data of varying noise levels and local field
      potentials recorded from the subthalamic nucleus of a Parkinson's disease
      patient.

PMID- 21871490
TI  - Microscopic magnetic resonance elastography of traumatic brain injury model.
AB  - Traumatic brain injury (TBI) is a major cause of death and disability for which
      there is no cure. One of the issues inhibiting clinical trial success is the lack
      of targeting specific patient populations due to inconsistencies between clinical
      diagnostic tools and underlying pathophysiology. The development of reliable,
      noninvasive markers of TBI severity and injury mechanisms may better identify
      these populations, thereby improving clinical trial design. Magnetic resonance
      elastography (MRE), by assessing tissue mechanical properties, can potentially
      provide such marker. MRE synchronizes mechanical excitations with a phase
      contrast imaging pulse sequence to noninvasively register shear wave propagation,
      from which local values of tissue viscoelastic properties can be deduced. The
      working hypothesis of this study is that TBI involves a compression of brain
      tissue large enough to bring the material out of its elastic range, sufficiently
      altering mechanical properties to generate contrast on MRE measurements. To test
      this hypothesis, we combined microscopic MRE with brain tissue collected from
      adult male rats subjected to a controlled cortical impact injury. Measurements
      were made in different regions of interest (somatosensory cortex, hippocampus,
      and thalamus), and at different time points following the injury (immediate, 24
      h, 7 days, 28 days). Values of stiffness in the somatosensory cortex were found
      to be 23-32% lower in the injured hemisphere than in the healthy one, when no
      significant difference was observed in the case of sham brains. A preliminary in
      vivo experiment is also presented, as well as alternatives to improve the
      faithfulness of stiffness recovery.

PMID- 21871491
TI  - Reliability of the 'observation of movement' method for determining motor
      threshold using transcranial magnetic stimulation.
AB  - The aim of this study was to establish the reliability of the observation of
      movement (OM) method for obtaining motor threshold (MT) in transcranial magnetic
      stimulation (TMS). MTs were obtained on separate days, following separate hunting
      procedures, for both left and right motor cortex (M1), with one or multiple
      estimates obtained from the same hemisphere within a single session. MTs obtained
      using the OM method were highly reliable and reproducible on different days (left
      M1: r=.98, p<.0001; right M1: r=.97, p<.0001). MTs were not influenced by the
      order of acquisition when two hemispheres were stimulated in the same session
      [F(1,22)=.12, p=.73] or by the collection of additional MTs as part of the
      distance-adjusted procedure [F(1,23)=.74, p=.40]. The results verify the
      reliability of the OM method and confirm its viability for the safe and efficient
      application of TMS to the left and right M1. The OM method is a reliable
      technique for obtaining MT and is relatively simple and quick to run. It
      therefore provides an effective procedure for research and clinical applications.

PMID- 21871492
TI  - Modified flow- and oxygen-related autoregulation indices for continuous
      monitoring of cerebral autoregulation.
AB  - Continuous monitoring of brain tissue partial pressure of oxygen (ptiO(2)),
      thermal-diffusion regional cerebral blood flow (TD-rCBF) and cerebral perfusion
      pressure (CPP) allows the calculation of flow- and oxygen-related autoregulation
      indices ORx and FRx. The influence of temporal phase shifts on ORx and FRx due to
      a delay in the response time of ptiO(2) and TD-rCBF has received little
      attention. We investigated the impact of phase shifts between changes in CPP and
      the corresponding ptiO(2) and TD-rCBF responses on the degree of correlation of
      ORx and FRx. In five patients with aneurysmal subarachnoid hemorrhage continuous
      multimodal neuromonitoring was performed for 7-10 days. In each patient the phase
      shift of the ptiO(2)- and TD-rCBF-response after spontaneous positive or negative
      CPP fluctuations during two 1-h time periods of disturbed cerebral autoregulation
      was determined. For these periods, ORx and FRx were calculated as Pearson
      correlation coefficients before (ORx and FRx) and after (ORx(sync) and FRx(sync))
      temporal synchronization of ptiO(2), TD-rCBF and CPP. The mean temporal phase
      shift after CPP fluctuations was 65+/-11 s for ptiO(2) and 12+/-4 s for TD-rCBF.
      Before synchronization, ORx and FRx were determined at 0.52+/-0.3 and 0.59+/-0.3,
      respectively. After synchronization, ORx(sync) and FRx(sync) correlated
      significantly stronger than unsynchronized indices (ORx(sync): 0.66+/-0.3;
      FRx(sync): 0.62+/-0.3; p<0.01 vs. ORx and FRx, respectively). These findings
      suggest that ORx and FRx are subject to temporal latency shifts of ptiO(2) and TD
      rCBF in regard to spontaneous CPP fluctuations. Temporal synchronization for the
      calculation of both ORx and FRx may permit continuous monitoring of these indices
      with higher sensitivity.

PMID- 21871493
TI  - Piezo controlled microinjection: an in vivo complement for in vitro sensory
      studies in insects.
AB  - Recent insights into insect olfactory signaling based on in vitro analyses have
      created an urgent need for equivalent in vivo analyses using living organisms.
      Here, we present a microinjection system that establishes a "virtual petri dish"
      within sensory structures for the application of agents to sensory neurons. Our
      system uses a series of pumps to inject chemical agents via air pressure into the
      surrounding lymph. We show using tetrodotoxin and forskolin application that
      robust effects on response dynamics of Drosophila melanogaster olfactory sensory
      neurons could be observed within 200 s, and suggest data analysis techniques to
      improve estimation of pharmacological effects on response kinetics. This approach
      provides an improved in vivo method to investigate questions in sensory neuron
      physiology as a complement to heterologous expression systems.

PMID- 21871494
TI  - Measuring burstiness and regularity in oscillatory spike trains.
AB  - The ability of neurons to emit different firing patterns such as bursts or
      oscillations is important for information processing in the brain. In
      dopaminergic neurons, prominent patterns include repetitive, oscillatory bursts,
      regular pacemakers, and irregular spike trains with nonstationary properties. In
      order to describe and measure the variability of these patterns, we describe
      burstiness and regularity in a single model framework. We present a doubly
      stochastic spike train model in which a background oscillation with independent
      and normally distributed intervals gives rise to either single spikes or bursty
      spike events with Gaussian firing intensities. Five easily interpretable
      parameters allow a classification into bursty or single spike and irregularly or
      regularly oscillating firing patterns. This classification is based primarily on
      features of the autocorrelation histogram which are usually studied qualitatively
      by visual inspection. The present model provides a quantitative and objective
      classification scheme and relates these features directly to the underlying
      processes. In addition, confidence intervals visualize the uncertainty of
      parameter estimation and classification precision. We apply the model to a data
      set obtained from single dopaminergic substantia nigra neurons recorded
      extracellularly in vivo. The model is able to represent a high variety of
      discharge patterns observed empirically, and the classification agrees closely
      with visual inspection. In addition, changes in the parameters can be studied
      quantitatively, including also the properties related to bursting behavior. Thus,
      the proposed model can be used for the description of neuronal firing patterns
      and the investigation of their dynamical changes with cellular and experimental
      conditions.

PMID- 21871495
TI  - Development of a minimally-invasive protocol for recording mismatch negativity
      (MMN) in the dog (Canis familiaris) using electroencephalography (EEG).
AB  - Mismatch negativity (MMN), observed in event-related potentials (ERPs),
      constitutes a measurable change in electrophysiological brain activity occurring
      after exposure to a novel stimulus. In humans, MMN is considered to be related to
      stimulus discrimination at the cortical level. ERP recording in dogs may present
      an opportunity to increase understanding of cognitive processes without reliance
      on observable behaviour, which may be confounded by motivation or training.
      Preliminary data are presented suggesting the existence of MMN, recorded using a
      minimally-invasive procedure equivalent to that used in humans, in unrestrained,
      unanaesthetised dogs. This is the first example of this ERP component in dogs and
      the method has substantial utility for future research exploring auditory,
      olfactory, and visual discrimination tasks, development, and breed differences.

PMID- 21871496
TI  - The use of real-time PCR to detect hepatitis C virus RNA in dried blood spots
      from Brazilian patients infected chronically.
AB  - Collecting and transporting samples for RNA analysis can be challenging,
      especially in situations where financial resources are limited. In this study, a
      quantitative real-time PCR (qPCR) for the analysis of HCV RNA was developed and
      adapted for use with dried blood spot (DBS) samples. A qPCR for HCV 5'NCR, an
      internal control and a calibration curve were developed, and the sensitivity,
      specificity and dynamic range of amplification were evaluated using a panel of
      viruses. Plasma and DBS samples from 100 patients who had completed four weeks of
      Peginterferon alfa-2b+Ribavirin treatment were collected (DBS on SS903 collection
      cards and transported at room temperature). After 24 weeks of treatment, samples
      were collected from 68 of these patients. Of the 168 samples, 2 yielded false
      negative results, and 4 yielded false-positive results (sensitivity was 98%,
      specificity was 94.3%, positive predictive value was 96.1%, and negative
      predictive value was 96.9%). Additionally, 2039 DBS samples from 1114 patients
      currently undergoing treatment for a chronic HCV infection in a clinical trial
      were tested. Only 10 samples out of the 2039 yielded invalid results warranting
      re-collection of DBS. The detection of HCV RNA in DBS can be a cost-effective
      strategy for HCV treatment monitoring, especially in settings where resources are
      limited.

PMID- 21871497
TI  - The main hepatitis B virus (HBV) mutants resistant to nucleoside analogs are
      susceptible in vitro to non-nucleoside inhibitors of HBV replication.
AB  - Long-term treatment of chronic hepatitis B with nucleos(t)ide analogs can lead to
      the emergence of HBV resistant mutants of the polymerase gene. The development of
      drugs with a different mode of action is warranted to prevent antiviral drug
      resistance. Only a few non-nucleosidic molecules belonging to the family of
      phenylpropenamides (AT-61 & AT-130) and heteroaryldihydropyrimidines (BAY41-4109)
      can prevent RNA encapsidation or destabilize nucleocapsids, respectively. The
      sensitivity of the main nucleos(t)ide analog- resistant mutants to these
      inhibitors was evaluated in vitro. HepG2 stable cell lines permanently expressing
      wild type (WT) HBV or the main HBV mutants resistant to lamivudine and/or
      adefovir (rtL180M+rtM204V, rtV173L+rtL180M+rtM204V, rtM204I, rtL180M+rtM204I,
      rtN236T, rtA181V, rtA181V+rtN236T, rtA181T, rtA181T+rtN236T) were treated with AT
      61, AT-130 or BAY-41 4109. Analysis of intracellular encapsidated viral DNA
      showed that all mutants were almost as sensitive to these molecules as WT HBV;
      indeed, the fold-resistance ranged between 0.7 and 2.3. Furthermore, the effect
      of a combination of either AT-61 or AT-130 with BAY41-4109, and the combination
      of these compounds with tenofovir was studied on wild type HBV as well as on a
      lamivudine and an adefovir-resistant mutant (rtL180M+M204V and rtN236T,
      respectively). These combinations of compounds resulted in inhibition of viral
      replication but showed slight antagonistic effects on the three HBV species.
      Based on this in vitro study, BAY-41 4109, AT-61 and AT-130 molecules that
      interfere with capsid morphogenesis are active against the main lamivudine- and
      adefovir-resistant mutants. These results suggest that targeting nucleocapsid
      functions may represent an interesting approach to the development of novel HBV
      inhibitors to prevent and combat drug resistance.

PMID- 21871498
TI  - Impaired sensitivity to Pavlovian stimulus-outcome learning after excitotoxic
      lesion of the ventrolateral neostriatum.
AB  - Subregions of the neostriatum have been dissociated according to their role in
      specific aspects of instrumental and Pavlovian learning. While the dorsomedial
      striatum is critical for the acquisition of goal-directed behaviours, the
      dorsolateral striatum has been shown to be necessary for the formation of habits.
      The ventrolateral subregion of the neostriatum (VLS), which supports a distinct
      cortical-subcortical circuitry, has not, however, been investigated within these
      paradigms. Thus, to determine whether the VLS is involved in the formation of
      action-outcome associations, Experiment 1 used a sensory specific devaluation
      procedure to assess the role of the VLS in the acquisition of goal-directed
      instrumental behaviours. Experiment 2 examined the ability of VLS lesion rats to
      form Pavlovian-outcome associations and to adjust responses according to the
      current incentive value of the reward by using a Pavlovian approach task, while
      Experiment 3 assessed the development and expression of habitual responding.
      Results indicated an intact ability of both sham and VLS lesion rats to form
      instrumental action-outcome associations and to use such representations to
      direct behaviour according to the incentive value of the outcome. VLS lesion rats
      equally demonstrated intact development of habitual lever press responses, which
      were shown to be impervious to lithium chloride devaluation treatment. VLS lesion
      rats did, however, demonstrate aberrant goal-directed responding to a Pavlovian
      auditory stimulus after outcome specific devaluation treatment. Thus, these
      results indicate that the VLS is necessary for utilising a representation of a
      Pavlovian stimulus-outcome association to direct behaviour according to the
      current incentive value of a reward.

PMID- 21871499
TI  - Higher inherent fearfulness potentiates the effects of chronic stress in the
      Japanese quail.
AB  - There is considerable variability in the susceptibility of individuals to the
      adverse effects of chronic stress. In humans and other mammals, individual traits
      such as high anxiety are proposed as a vulnerability factor for the development
      of stress-related disorders. In the present study, we tested whether a similar
      behavioural trait in birds, higher emotional reactivity, also favours the
      occurrence of chronic stress-related behavioural and physiological dysfunction.
      For this, lines of Japanese quail divergently selected for a typical fear
      response in birds, the duration of tonic immobility, were subjected to
      unpredictable aversive stimulation over 2 weeks. Previous studies demonstrate
      that the selection program modifies the general underlying emotionality of the
      birds rather than exerting its effect only on tonic immobility. Interestingly,
      only birds selected for their higher emotionality exhibited significantly
      enhanced latency to first step and decreased locomotor activity in the open-field
      test after exposure to chronic stress compared to non-stressed control birds.
      This effect of chronic stress was selective for the tested dimension of bird
      emotional reactivity because there was no observed effect on the tonic immobility
      response. Moreover, chronically stressed birds selected for their higher
      emotionality exhibited significantly decreased basal corticosterone levels, a
      physiological marker of stress. These findings show that chronic stress is
      associated with changes in emotional reactivity and related physiological markers
      in birds. They also highlight emotional reactivity as an important predisposing
      factor for the occurrence of the adverse effects of chronic stress in birds.

PMID- 21871500
TI  - Dopamine D1 receptor antagonism impairs extinction of cocaine-cue memories.
AB  - Increasingly, research suggests a role for dopamine D1 receptors in the
      consolidation of extinction of both appetitive and aversive memories. However, a
      role for D1 receptors in extinction of memories involving drug reward has yet to
      be established. Here we show that post-retrieval, but not delayed, systemic
      administration of the D1 receptor antagonist SCH23390 results in prolonged
      extinction of cocaine conditioned place preference (CPP), suggesting a critical
      role for D1 receptors in the consolidation of extinction of cocaine-cue memories.

PMID- 21871501
TI  - Roles for HIF-1alpha in neural stem cell function and the regenerative response
      to stroke.
AB  - Stroke represents a leading cause of long-term disability worldwide, with few
      therapeutic options available for improving behavioral recovery. Identification
      of endogenous neural stem and progenitor cells (NSPCs) that are capable of
      promoting reparative responses following brain injury and stroke make these cells
      attractive therapeutic targets for stimulating cell replacement and neuronal
      plasticity. Interest in the mechanisms that support NSPC survival and
      replenishment of damaged cells within the ischemic brain has led to elucidation
      of new roles for hypoxia-inducible factor-1alpha (HIF-1alpha) in NSPC function.
      HIF-1alpha is a well-studied mediator of adaptive cellular responses to hypoxia
      through direct transcriptional regulation of cellular metabolism and
      angiogenesis. Recent evidence also indicates novel roles for HIF-1alpha in stem
      cell differentiation through modulation of Notch and Wnt/beta-catenin signaling
      pathways. In this review, we will explore the hypothesis that HIF-1alpha
      represents an important mediator of NSPC function under both non-pathological
      conditions and stroke; and plays a central role in the regulation of NSPC
      response to hypoxia, metabolism and maintenance of the vascular environment of
      the neural stem cell niche.

PMID- 21871503
TI  - Attentional biases among body-dissatisfied young women: an ERP study with rapid
      serial visual presentation.
AB  - In the current study, rapid serial visual presentation (RSVP) task combined with
      event related potentials (ERP) was used to investigate attention biases toward
      body-related words in a nonclinical sample of body dissatisfied females.
      Consistent with the hypotheses, the amplitudes of N100, N170 and P3 are sensitive
      to different body-related words in the RSVP paradigm only among body weight
      dissatisfied women (WD group), while control group did not show this difference.
      The early anterior N100 and bi-lateral parietal and occipital N170 amplitudes
      elicited by fatness-related words were larger than those elicited by thinness
      related and neutral words among WD group, a finding which is consistent with the
      presence of a 'negativity bias'. Also, WD group women showed significantly
      different amplitudes in response to three categories of stimuli with thin words
      eliciting the largest P3 amplitudes, followed by fat words and the least neutral
      words. The current findings indicated that attention biases toward body weight
      related words were evident during both sensory and cognitive stages of
      information processing. Findings are also consistent with hypotheses of cognitive
      behavioral accounts of body weight dissatisfaction which propose, in part, that
      individual differences on cognitive tasks reveal underlying psychopathology;
      attentional biases reflect disordered body schema, not disordered eating, and can
      therefore be seen in non-clinical samples.

PMID- 21871502
TI  - Quality control and fate determination of Hsp90 client proteins.
AB  - Quality control processes regulate the proteome by determining whether a protein
      is to be folded or degraded. Hsp90 is a hub in the network of molecular
      chaperones that maintain this process because it promotes both folding and
      degradation, in addition to regulating expression of other quality control
      components. The significance of Hsp90's role in quality control is enhanced by
      the function of its clients, which include protein kinases and transcription
      factors, in cellular signaling. The inhibition of Hsp90 with small molecules
      results in the rapid degradation of such clients via the ubiquitin/proteasome
      pathway, and also in the induction of the Hsp70 molecular chaperone. These two
      events result in markedly different outcomes depending on cell type. For tumor
      cells there is a profound loss of signaling in growth promoting pathways. By
      contrast, increased amounts of Hsp70 in neuronal cells ameliorate the toxicity
      that is associated with the formation of aggregates observed in neurodegenerative
      conditions. In this review we discuss the mechanisms underlying these
      differential effects of Hsp90 inhibition on the quality control of distinct
      client proteins. This article is part of a Special Issue entitled: Heat Shock
      Protein 90 (HSP90).

PMID- 21871504
TI  - Host factors mediating HIV-1 replication.
AB  - Human immunodeficiency virus type 1(HIV-1) infection is the leading cause of
      death worldwide in adults attributable to infectious diseases. Although the
      majority of infections are in sub-Saharan Africa and Southeast Asia, HIV-1 is
      also a major health concern in most countries throughout the globe. While current
      antiretroviral treatments are generally effective, particularly in combination
      therapy, limitations exist due to drug resistance occurring among the drug
      classes. Traditionally, HIV-1 drugs have targeted viral proteins, which are
      mutable targets. As cellular genes mutate relatively infrequently, host proteins
      may prove to be more durable targets than viral proteins. HIV-1 replication is
      dependent upon cellular proteins that perform essential roles during the viral
      life cycle. Maraviroc is the first FDA-approved antiretroviral drug to target a
      cellular factor, HIV-1 coreceptor CCR5, and serves to intercept viral-host
      protein-protein interactions mediating entry. Recent large-scale siRNA and shRNA
      screens have revealed over 1000 candidate host factors that potentially support
      HIV-1 replication, and have implicated new pathways in the viral life cycle.
      These host proteins and cellular pathways may represent important targets for
      future therapeutic discoveries. This review discusses critical cellular factors
      that facilitate the successive steps in HIV-1 replication.

PMID- 21871505
TI  - EGFR-targeted stearoyl gemcitabine nanoparticles show enhanced anti-tumor
      activity.
AB  - Previously, it was shown that a novel 4-(N)-stearoyl gemcitabine nanoparticle
      formulation was more effective than gemcitabine hydrochloride in controlling the
      growth of model mouse or human tumors pre-established in mice. In the present
      study, the feasibility of targeting the stearoyl gemcitabine nanoparticles
      (GemC18-NPs) into tumor cells that over-express epidermal growth factor receptor
      (EGFR) to more effectively control tumor growth was evaluated. EGFR is over
      expressed in a variety of tumor cells, and EGF is a known natural ligand of EGFR.
      Recombinant murine EGF was conjugated onto the GemC18-NPs. The ability of the EGF
      to target the GemC18-NPs to human breast adenocarcinoma cells that expressed
      different levels of EGFR was evaluated in vitro and in vivo. In culture, the
      extent to which the EGF-conjugated GemC18-NPs were taken up by tumor cells was
      correlated to the EGFR density on the tumor cells, whereas the uptake of
      untargeted GemC18-NPs exhibited no difference among those same cell lines. The
      relative cytotoxicity of the EGF-conjugated GemC18-NPs to tumor cells in culture
      was correlated to EGFR expression as well. In vivo, EGFR-over-expressing MDA-MB
      468 tumors in mice treated with the EGF-conjugated GemC18-NPs grew significantly
      slower than in mice treated with untargeted GemC18-NPs, likely due to that the
      EGF-GemC18-NPs were more anti-proliferative, anti-angiogenic, and pro-apoptotic.
      Fluorescence intensity data from ex vivo imaging showed that the EGF on the
      nanoparticles helped increase the accumulation of the GemC18-NPs into MDA-MB-468
      tumors pre-established in mice by more than 2-fold as compared to the un-targeted
      GemC18-NPs. In conclusion, active targeting of the GemC18-NPs into EGFR-over
      expressed tumors can further enhance their anti-tumor activity.

PMID- 21871506
TI  - Cancer treatment using an optically inert Rose Bengal derivative combined with
      pulsed focused ultrasound.
AB  - Pulsed high intensity focused ultrasound (HIFU) has been combined with a photo
      insensitive Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity
      requiring the presence of both ultrasonic cavitation and drug. In vitro tests
      have shown that a short treatment (less than 30 s) of pulsed HIFU with peak
      negative pressure >7 MPa (~27 W acoustic power at 1.4 MHz) destroys >95% of
      breast cancer cells MDA-MB-231 in suspension with >10 MUM of the compound.
      Neither the pulsed HIFU nor the RB2 compound was found to have any significant
      impact on the viability of the cells when used alone. Introducing an antioxidant
      (N-acetylcysteine) reduced the effectiveness of the treatment. In vivo tests
      using these same cells growing as a xenograft in nu/nu mice were also done. An
      ultrasound contrast agent (Optison) and lower frequency (1.0 MHz) was used to
      help initiate cavitation at the tumor site. We were able to demonstrate tumor
      regression with cavitation alone, however, addition of RB2 compound injected i.v.
      yielded a substantial synergistic improvement.

PMID- 21871508
TI  - Multiple aspects of the interaction of biomacromolecules with inorganic surfaces.
AB  - The understanding of the mechanisms involved in the interaction of biological
      systems with inorganic materials is of interest in both fundamental and applied
      disciplines. The adsorption of proteins modulates the formation of biofilms onto
      surfaces, a process important in infections associated to medical implants, in
      dental caries, in environmental technologies. The interaction with
      biomacromolecules is crucial to determine the beneficial/adverse response of
      cells to foreign inorganic materials as implants, engineered or accidentally
      produced inorganic nanoparticles. A detailed knowledge of the surface/biological
      fluids interface processes is needed for the design of new biocompatible
      materials. Researchers involved in the different disciplines face up with similar
      difficulties in describing and predicting phenomena occurring at the interface
      between solid phases and biological fluids. This review represents an attempt to
      integrate the knowledge from different research areas by focussing on the search
      for determinants driving the interaction of inorganic surfaces with biological
      matter.

PMID- 21871507
TI  - Nanoparticle delivery of a peptide targeting EGFR signaling.
AB  - EGFR serves as an important therapeutic target because of its over-expression in
      many cancers. In this study, we investigated a peptide-based therapy aimed at
      blocking intracellular protein-protein interactions during EGFR signaling and
      evaluated a targetable lipid carrier system that can deliver peptides to
      intracellular targets in human cancer cells. EEEEpYFELV (EV), a nonapeptide
      mimicking the Y845 site of EGFR which is responsible for STAT5b phosphorylation,
      was designed to block EGFR downstream signaling. EV was loaded onto LPH
      nanoparticles that are comprised of a membrane/core structure including a surface
      grafted polyethylene glycol (PEG) used to evade the reticuloendothelial system
      (RES) and anisamide (AA) for targeting the sigma receptor over-expressed in H460
      human lung cancer cells. EV formulated with PEGylated and targeted LPH (LPH-PEG
      AA) was taken up by the tumor cells and trafficked to the cytoplasm with high
      efficiency. Using this approach, EV acted as a dominant negative inhibitor of
      STAT5b phosphorylation, arrested cell proliferation, and induced massive
      apoptosis. Intravenous administration of EV loaded in LPH-PEG-AA led to efficient
      EV peptide delivery to the tumor in a xenograft mouse model, and multiple
      injections inhibited tumor growth in a dose-dependent manner. Our findings offer
      proof-of-concept for an intracellular peptide-mediated cancer therapy that is
      delivered by carefully designed nanoparticles.

PMID- 21871509
TI  - Texture, not flavor, determines expected satiation of dairy products.
AB  - Consumers' expectations about the satiating capacity of a food may differ
      markedly across a broad range of food products, but also between foods within one
      product category. Our objective is to investigate the role of sensory attributes
      and means of consumption in the expected satiation of dairy products. In three
      independent experiments we measured the expected satiation of (1) commercially
      available yogurts and custards (29 adults, age: 26 +/- 5 y, BMI: 22.9 +/- 2.4
      kg/m(2)); (2) lemon- and meringue-flavored custards with different textures (30
      adults, age: 23 +/- 4 y, BMI: 22.1 +/- 2.1 kg/m(2)); and (3) chocolate milk and
      chocolate custard consumed with either a straw or a spoon (30 adults, age: 20 +/-
      2.2 y, BMI: 21.5 +/- 2.2 kg/m(2)); all based on a single mouthful. Expected
      satiation was linked to the product's perceived characteristics. We observed an
      effect of texture (p<0.0001), but not of flavor on expected satiation (p=0.98) in
      Experiment 2; and an effect of texture (p<0.0001), but not of means of
      consumption on expected satiation (p=0.63) in Experiment 3. Thickness was
      positively correlated with expected satiation in Experiment 1 (r=0.45; p<0.001)
      and Experiment 2 (r=0.54; p<0.001). Expected satiation of dairy products
      increased consistently with increasing thickness; flavor characteristics or means
      of consumption as tested did not change expected satiation effects.

PMID- 21871511
TI  - Combined anti-inflammatory effects of beta2-adrenergic agonists and PDE4
      inhibitors on astrocytes by upregulation of intracellular cAMP.
AB  - Inflammation is an important hallmark of all neurodegenerative diseases and
      activation of different glial populations may be involved in the progression of
      some of these disorders. Especially, the activation of astroglia can lead to long
      term detrimental morphological changes, such as scar formation. Therefore,
      improved strategies to modulate inflammation in these cells are currently being
      investigated. We investigated the interaction of phosphodiesterase (PDE) 4
      inhibitors, such as rolipram, with other agents raising cellular cAMP levels.
      When used alone, none of the PDE4 inhibitors increased cAMP levels. The adenylate
      cyclase activator forskolin, the beta(2)-adrenergic agonist clenbuterol and the
      mixed beta(1)/beta(2)-adrenergic agonist isoproterenol increased intracellular
      cAMP levels of cortical murine astrocytes. This increase was synergistically
      elevated by rolipram or the PDE4 inhibitor RO-201724, but not by inhibition of
      PDE3. Inflammatory stimulation of the cells with the cytokines TNF-alpha, IL
      1beta and IFN-gamma strongly induced PDE4B and augmented overall PDE4 activity,
      while PDE3 activity was low. Clenbuterol and forskolin caused downregulation of
      cytokines and chemokines such as IL-6 and MCP-1. This effect was further enhanced
      by rolipram, but not by the PDE3 inhibitor milrinone. The cAMP-raising drug
      combinations attenuated the upregulation of TNF-alpha and IL-6 mRNA and the
      secretion of IL-6, but did not affect initial NF-kappaB signalling triggered by
      the stimulating cytokines. These results indicate that PDE4 may be a valuable
      anti-inflammatory target in brain diseases, especially under conditions
      associated with stimulation of cAMP-augmenting astrocyte receptors as is observed
      by clenbuterol treatment.

PMID- 21871512
TI  - Dopamine release and molecular modeling study of some coumarin derivatives.
AB  - 4-aryl-2-amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitrile (1), 4
      aryl-2-oxo-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitriles (2a-2c), 3
      (6-aryl-1,2,5,6- tetrahydro-2-thioxopyrimidin-4-yl)-4-hydroxy-2H-chromen-2-one
      (3a, 3b) and pyrazol-3-yl-4-hydroxycoumarin derivatives (4a-4c, 5, 6a, 6b, 7a,
      7b, and 8a-8c) were prepared in order to measure their % change dopamine release
      in comparison to amphetamine as reference, using PC-12 cells in different
      concentrations. In addition, the molecular modeling study of the compounds into
      3BHH receptor was also demonstrated. The calculated inhibition constant (k(i))
      implemented in the AutoDock program revealed identical correlation with the
      experimental results to that obtained binding free energy (DeltaG(b)) as both
      parameters revealed reasonable correlation coefficients (R(2)) being 0.51
      involving 10 compounds; (1, 2b, 2c, 3a, 3b, 4a, 4b, 6a, and 8c).

PMID- 21871510
TI  - An integrin-binding N-terminal peptide region of TIMP-2 retains potent angio
      inhibitory and anti-tumorigenic activity in vivo.
AB  - Tissue inhibitor of metalloproteinases-2 (TIMP-2) inhibits angiogenesis by
      several mechanisms involving either MMP inhibition or direct endothelial cell
      binding. The primary aim of this study was to identify the TIMP-2 region involved
      in binding to the previously identified receptor integrin alpha3beta1, and to
      determine whether synthetic peptides derived from this region retained angio
      inhibitory and tumor suppressor activity. We demonstrated that the N-terminal
      domain of TIMP-2 (N-TIMP-2) binds to alpha3beta1 and inhibits vascular
      endothelial growth factor-stimulated endothelial cell growth in vitro, suggesting
      that both the alpha3beta1-binding domain and the growth suppressor activity of
      TIMP-2 localize to the N-terminal domain. Using a peptide array approach we
      identify a 24 amino acid region of TIMP-2 primary sequence, consisting of
      residues Ile43-Ala66, which shows alpha3beta1-binding activity. Subsequently we
      demonstrate that synthetic peptides from this region compete for TIMP-2 binding
      to alpha3beta1 and suppress endothelial growth in vitro. We define a minimal
      peptide sequence (peptide 8-9) that possesses both angio-inhibitory and, using a
      murine xenograft model of Kaposi's sarcoma, anti-tumorigenic activity in vivo.
      Thus, both the alpha3beta1-binding and the angio-inhibitory activities co
      localize to a solvent exposed, flexible region in the TIMP-2 primary sequence
      that is unique in amino acid sequence compared with other members of the TIMP
      family. Furthermore, comparison of the TIMP-2 and TIMP-1 protein 3-D structures
      in this region also identified unique structural differences. Our findings
      demonstrate that the integrin binding, tumor growth suppressor and in vivo angio
      inhibitory activities of TIMP-2 are intimately associated within a unique
      sequence/structural loop (B-C loop).

PMID- 21871513
TI  - Overhauser-enhanced magnetic resonance imaging characterization of mitochondria
      functional changes in the 6-hydroxydopamine rat model.
AB  - Oxidative stress may be involved in the dopaminergic neurodegenerations seen in 6
      OHDA-lesioned rats through its production of free radicals and through
      mitochondrial dysfunction. In this study, we noninvasively demonstrate brain
      redox alterations in 6-OHDA-lesioned rats using Overhauser-enhanced magnetic
      resonance imaging (OMRI). The reduction rate of 3-methoxycarbonyl-2,2,5,5
      tetramethylpyrrolidine-l-oxyl (methoxycarbonyl-PROXYL), a redox-sensitive
      contrast agent, was used as an index of the redox status in vivo. The
      methoxycarbonyl-PROXYL reduction rate, calculated from continuous images,
      decreased significantly in lesioned hemispheres compared to their corresponding
      contralateral hemispheres. The reduction rates in cellular fractions obtained
      from the striatum were estimated by X-band electron spin resonance (ESR) and
      calculated by assuming first-order kinetics for their time-dependent decreases.
      When methoxycarbonyl-PROXYL was mixed with cytoplasm fractions, the reduction
      rates were the same in both hemispheres. However, the ESR signal of
      methoxycarbonyl-PROXYL in the mitochondrial fraction of the lesioned hemispheres
      decayed more slowly than that of the corresponding contralateral hemispheres.
      Concordantly, biochemical assays showed that the activity of mitochondrial
      complex I also decreased more slowly in lesioned hemispheres. Thus, this method
      of noninvasively imaging brain redox alterations faithfully reflects changes in
      mitochondrial complex I activity in 6-OHDA-lesioned rats.

PMID- 21871514
TI  - Intracerebroventricular administration of ouabain, a Na/K-ATPase inhibitor,
      activates tyrosine hydroxylase through extracellular signal-regulated kinase in
      rat striatum.
AB  - Alteration in dopamine neurotransmission has been reported to be involved in the
      mania of bipolar disorder. Tyrosine hydroxylase (TH) is the rate-limiting enzyme
      that is crucial for dopamine biosynthesis, and its activity is tightly regulated
      by phosphorylation at multiple N-terminal serine residues. Previously, we have
      reported that intracerebroventricular (ICV) injection of ouabain, a selective
      Na/K-ATPase inhibitor, induces hyperactivity in rats that mimics manic symptoms
      related to the activation of extracellular signal-regulated protein kinase1/2
      (ERK1/2), which plays crucial roles in the modulation of TH phosphorylation. In
      this study, we investigated the effects of ICV injection of ouabain on TH
      phosphorylation in rat striatum and the involvement of ERK1/2 in ouabain-induced
      TH activation. ICV ouabain induced an acute dose-dependent increase in locomotor
      activity and in TH phosphorylation in rat striatum. TH phosphorylation at Ser19
      was significantly increased with 100, 500, and 1000MUM ouabain, and
      phosphorylation at Ser31 and Ser40 was significantly increased with 500 and
      1000MUM. We also found that ICV pretreatment with U0126, a specific MEK1/2
      inhibitor, attenuated the 1000MUM ouabain-induced increase in TH phosphorylation
      at Ser19, Ser31, and Ser40, as well as the hyperactivity of rats. Moreover, the
      increased phosphorylation of TH (Ser19, Ser31, and Ser40) was maintained until 8h
      after single administration ouabain was accompanied by increased phosphorylation
      of ERK1/2 (Thr202/Tyr204) and p90RSK (Thr359/Ser363). These findings imply that
      TH activation of the ERK1/2 signal pathway could play an important role in
      ouabain-induced hyperactivity of rats, a mania model.

PMID- 21871515
TI  - Improved long-term protection against Mycobacterium tuberculosis Beijing/W in
      mice after intra-dermal inoculation of recombinant BCG expressing latency
      associated antigens.
AB  - Bacille Calmette-Guerin (BCG) is the vaccine against tuberculosis (TB), but has
      varied efficacy in different geographical locations. Recombinant strategies to
      genetically modify the organism to enhance the quality of the immune response
      have aimed at improving BCG efficacy. Here we describe such a strategy using
      rBCGDeltaureC?hly expressing defined latency-associated antigens and test this
      construct for long-term protection against an isolate of the Mycobacterium
      tuberculosis (Mtb) Beijing/W lineage. Expression of the antigens Rv2659c, Rv3407
      and Rv1733c by rBCGDeltaureC?hly improved long-term efficacy in both lung and
      spleen at day 200 post-infection after intradermal vaccination of mice. Our data
      support expression of Mtb latency associated antigens by rBCG to improve
      protection against Mtb.

PMID- 21871516
TI  - Evaluation of growth based rapid microbiological methods for sterility testing of
      vaccines and other biological products.
AB  - Most biological products, including vaccines, administered by the parenteral
      route are required to be tested for sterility at the final container and also at
      various stages during manufacture. The sterility testing method described in the
      Code of Federal Regulations (21 CFR 610.12) and the United States Pharmacopoeia
      (USP, Chapter <71>) is based on the observation of turbidity in liquid culture
      media due to growth of potential contaminants. We evaluated rapid microbiological
      methods (RMM) based on detection of growth 1) by adenosine triphosphate (ATP)
      bioluminescence technology (Rapid Milliflex((r)) Detection System [RMDS]), and 2)
      by CO(2) monitoring technologies (BacT/Alert and the BACTEC systems), as
      alternate sterility methods. Microorganisms representing Gram negative, Gram
      positive, aerobic, anaerobic, spore forming, slow growing bacteria, yeast, and
      fungi were prepared in aliquots of Fluid A or a biological matrix (including
      inactivated influenza vaccines) to contain approximately 0.1, 1, 10 and 100
      colony forming units (CFU) in an inoculum of 10 ml. These preparations were
      inoculated to the specific media required for the various methods: 1) fluid
      thioglycollate medium (FTM) and tryptic soy broth (TSB) of the compendial
      sterility method (both membrane filtration and direct inoculation); 2) tryptic
      soy agar (TSA), Sabouraud dextrose agar (SDA) and Schaedler blood agar (SBA) of
      the RMDS; 3) iAST and iNST media of the BacT/Alert system and 4) Standard 10
      Aerobic/F and Standard Anaerobic/F media of the BACTEC system. RMDS was
      significantly more sensitive in detecting various microorganisms at 0.1CFU than
      the compendial methods (p<0.05), whereas the compendial membrane filtration
      method was significantly more sensitive than the BACTEC and BacT/Alert methods
      (p<0.05). RMDS detected all microorganisms significantly faster than the
      compendial method (p<0.05). BacT/Alert and BACTEC methods detected most
      microorganisms significantly faster than the compendial method (p<0.05), but took
      almost the same time to detect the slow growing microorganism P. acnes, compared
      to the compendial method. RMDS using SBA detected all test microorganisms in the
      presence of a matrix containing preservative 0.01% thimerosal, whereas the
      BacT/Alert and BACTEC systems did not consistently detect all the test
      microorganisms in the presence of 0.01% thimerosal. RMDS was compatible with
      inactivated influenza vaccines and aluminum phosphate or aluminum hydroxide
      adjuvants at up to 8 mg/ml without any interference in bioluminescence. RMDS was
      shown to be acceptable as an alternate sterility method taking 5 days as compared
      to the 14 days required of the compendial method. Isolation of microorganisms
      from the RMDS was accomplished by re-incubation of membranes with fresh SBA
      medium and microbial identification was confirmed using the MicroSEQ
      Identification System. BacT/Alert and BACTEC systems may be applicable as
      alternate methods to the compendial direct inoculation sterility method for
      products that do not contain preservatives or anti-microbial agents.

PMID- 21871517
TI  - A naturally derived outer-membrane vesicle vaccine protects against lethal
      pulmonary Burkholderia pseudomallei infection.
AB  - Burkholderia pseudomallei, and other members of the Burkholderia, are among the
      most antibiotic-resistant bacterial species encountered in human infection.
      Mortality rates associated with severe B. pseudomallei infection approach 50%
      despite therapeutic treatment. A protective vaccine against B. pseudomallei would
      dramatically reduce morbidity and mortality in endemic areas and provide a
      safeguard for the U.S. and other countries against biological attack with this
      organism. In this study, we investigated the immunogenicity and protective
      efficacy of B. pseudomallei-derived outer membrane vesicles (OMVs). Vesicles are
      produced by Gram-negative and Gram-positive bacteria and contain many of the
      bacterial products recognized by the host immune system during infection. We
      demonstrate that subcutaneous (SC) immunization with OMVs provides significant
      protection against an otherwise lethal B. pseudomallei aerosol challenge in
      BALB/c mice. Mice immunized with B. pseudomallei OMVs displayed OMV-specific
      serum antibody and T-cell memory responses. Furthermore, OMV-mediated immunity
      appears species-specific as cross-reactive antibody and T cells were not
      generated in mice immunized with Escherichia coli-derived OMVs. These results
      provide the first compelling evidence that OMVs represent a non-living vaccine
      formulation that is able to produce protective humoral and cellular immunity
      against an aerosolized intracellular bacterium. This vaccine platform constitutes
      a safe and inexpensive immunization strategy against B. pseudomallei that can be
      exploited for other intracellular respiratory pathogens, including other
      Burkholderia and bacteria capable of establishing persistent infection.

PMID- 21871518
TI  - Modeling the decline in pneumococcal acute otitis media following the
      introduction of pneumococcal conjugate vaccines in the US.
AB  - We hypothesized that following the introduction of PCV7, the exchange of vaccine
      serotypes (VST) for non-vaccine serotypes (NVST) in the nasopharynx has resulted
      in fewer episodes of pneumococcal acute otitis media (AOM) due to the reduced
      capacity for common NVST strains to cause disease. We modeled the change in the
      proportion of children colonized with S. pneumoniae who would develop
      pneumococcal AOM that would occur due to serotype replacement, and projected the
      future impact of PCV13. Our model is based on observed changes in the
      nasopharyngeal pneumococcal serotype distribution from the pre- to post-PCV7 era,
      and an estimated capacity of each serotype to produce pneumococcal AOM given
      colonization; the latter was derived by dividing serotype-specific disease
      prevalence by serotype-specific carriage prevalence in the same population. Our
      results indicate a 12% (95% CI 0.5-26) decline in the number of AOM episodes
      attributable to S. pneumoniae in children less than 3 years of age between 2000
      and 2007 due to the combined effects of PCV7 vaccine efficacy and vaccine-induced
      serotype replacement, and predicts that PCV13 will further decrease pneumococcal
      AOM an additional 27% (95% CI 13-40) from 2007 to 2013. Evaluation of changes in
      VST disease revealed a 91% (95% CI 83-97) decrease in PCV7-VST AOM from 2000 to
      2007, and predicted an additional 65% (95% CI 57-74) decrease in PCV13-VST AOM
      from 2007 to 2013. Our model indicates that following vaccination, nasopharyngeal
      replacement of VST by NVST has led to a decrease in the amount of pneumococcal
      AOM despite a consistent rate of S. pneumoniae colonization, and that
      pneumococcal AOM may continue to decrease as pneumococcal serotypes with greater
      capacity to cause disease are replaced by less locally invasive serotypes.

PMID- 21871519
TI  - Effects of enoxaparin in the rat hippocampus following traumatic brain injury.
AB  - Purpose of this study was to investigate the effects of low molecular weight
      heparin, enoxaparin, on different parameters of the hippocampal damage following
      traumatic brain injury (TBI) in the rat. TBI of moderate severity was performed
      over the left parietal cortex using the lateral fluid percussion brain injury
      model. Animals were s.c. injected with either enoxaparin (1mg/kg) or vehicle 1,
      7, 13, 19, 25, 31, 37, and 43 h after the TBI induction. Sham-operated, vehicle
      treated animals were used as the control group. Rats were sacrificed 48h after
      the induction of TBI. Hippocampi were processed for spectrophotometric
      measurements of the products of oxidative lipid damage, thiobarbituric acid
      reactive substances (TBARS) levels, as well as the activities of antioxidant
      enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px).
      Moreover, the Western blotting analyses of the oxidized protein levels,
      expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS),
      pro- and mature-interleukin-1beta (pro-, and mature-IL-1beta), and active caspase
      3 were performed. COX-2 expressions were also explored by using
      immunohistochemistry. Glial fibrillary acidic protein immunochistochemistry was
      performed with the aim to assess the level of astrocytic activity. Fluoro-Jade B
      staining was used to identify the level and extent of hippocampal neuronal
      injury. TBI caused statistically significant increases of the hippocampal TBARS
      and oxidized protein levels as well as COX-2, pro-IL-1beta, and active caspase-3
      overexpressions, but it did not significantly affect the SOD and GSH-Px
      activities, the iNOS, and mature-IL-1beta expression levels. TBI also induced
      hippocampal reactive astrocytosis and neurodegeneration. Enoxaparin significantly
      decreased the hippocampal TBARS and oxidized protein levels, COX-2 overexpression
      and reactive gliosis, but it did not influence the SOD and GSH-Px activities, pro
      IL-1beta and active caspase-3 overexpressions as well as neurodegeneration
      following TBI. These findings demonstrate that enoxaparin may reduce oxidative
      damage, inflammation and astrocytosis following TBI in the rat and could be a
      candidate drug for neuroprotective treatment of this injury.

PMID- 21871520
TI  - Increasing the density of the D2L receptor and manipulating the receptor
      environment are required to evidence the partial agonist properties of
      aripiprazole.
AB  - The clinical efficacy of aripiprazole in the treatment of psychosis relies on a
      partial agonism at D2 receptors. As the expression of this receptor differs
      physiologically between pre- and post-synaptic sites and is affected by
      pathological conditions or pharmacological treatments, it appears difficult to
      predict the clinical response to partial agonists. In addition, the response to
      this novel antipsychotic was shown to depend on the cell-line and the pathway
      analyzed, suggesting a functional selective profile at the D2 receptor. This
      study aims at examining the influence of receptor density and ionic environment
      on the pharmacological properties of aripiprazole. A cell line was developed in
      which the expression of the recombinant D2 receptor can be tightly manipulated
      using doxycycline and sodium butyrate. The potency and efficacy of aripiprazole
      and other reference D2 receptor ligands were examined in [35S]GTPgammaS binding
      assays, in buffers containing either NaCl or N-methyl-D-glucamine (NMDG) which is
      proposed to enhance G protein coupling. Increasing the density of D2 receptors
      considerably enhanced the [35S]GTPgammaS binding induced by dopamine and the full
      agonist NPA. In maximally induced cells, the agonist properties of the partial
      agonist (-)-3-PPP was revealed in a buffer containing NaCl, whereas the response
      to aripiprazole was not evidenced. Substituting NMDG for NaCl promoted the
      response to dopamine and (-)3-PPP and was proven efficient to reveal the partial
      agonist profile of aripiprazole. While NMDG substitution for NaCl strongly
      enhanced receptor-G protein coupling, these ionic manipulations are likely to
      influence receptor conformations, thereby modulating the activation of signaling
      pathways. Our data obtained with partial agonists acting at the D2 receptor
      suggest that these changes in the experimental conditions could contribute to
      reveal the functional selective profile of GPCR ligands. They also emphasize that
      the properties of functional selective ligands do not only depend on receptor
      density but also on the surrounding environment which likely differs between
      brain structures.

PMID- 21871521
TI  - Application of ICP-MS method of determination of 15 elements in honey with
      chemometric approach for the verification of their authenticity.
AB  - In this study the mineral content of 140 honey samples, which represent three
      different types of honey, namely: honeydew, buckwheat and rape honey from 16
      areas of Poland, were evaluated. The method is described for determination of 15
      elements (Al, B, Ba, Ca, Cd, Cr, Cu, K, Mg, Mn, Na, Ni, Pb, Sr, and Zn) in honey
      from Poland using ICP-MS. The data were subjected to chemometric assessment to
      understand the association between the elements and classify honey samples.
      Mainly supervised pattern recognition techniques, such as LDA and C&RT were
      performed for the whole data set in order to discriminate and classify honey
      samples according to their origin and detect corresponding markers. Analyzes
      revealed an excellent separation between honey samples according to their type
      with the efficiency of LDA model as 100%. On the other hand, a variable
      classification for rape, buckwheat and honeydew honeys in regards to their
      geographical origin could be achieved.

PMID- 21871522
TI  - State of the art in benefit-risk analysis: economics and marketing-finance.
AB  - All market participants (e.g., investors, producers, consumers) accept a certain
      level of risk as necessary to achieve certain benefits. There are many types of
      risk including price, production, financial, institutional, and individual human
      risks. All these risks should be effectively managed in order to derive the
      utmost of benefits and avoid disruption and/or catastrophic economic consequences
      for the food industry. The identification, analysis, determination, and
      understanding of the benefit-risk trade-offs of market participants in the food
      markets may help policy makers, financial analysts and marketers to make well
      informed and effective corporate investment strategies in order to deal with
      highly uncertain and risky situations. In this paper, we discuss the role that
      benefits and risks play in the formation of the decision-making process of market
      participants, who are engaged in the upstream and downstream stages of the food
      supply chain. In addition, we review the most common approaches (expected utility
      model and psychometrics) for measuring benefit-risk trade-offs in the economics
      and marketing-finance literature, and different factors that may affect the
      economic behaviour in the light of benefit-risk analyses. Building on the
      findings of our review, we introduce a conceptual framework to study the benefit
      risk behaviour of market participants. Specifically, we suggest the decoupling of
      benefits and risks into the separate components of utilitarian benefits, hedonic
      benefits, and risk attitude and risk perception, respectively. Predicting and
      explaining how market participants in the food industry form their overall
      attitude in light of benefit-risk trade-offs may be critical for policy-makers
      and managers who need to understand the drivers of the economic behaviour of
      market participants with respect to production, marketing and consumption of food
      products.

PMID- 21871523
TI  - Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava
      Kava.
AB  - Kava Kava is an herbal supplement used as an alternative to antianxiety drugs.
      Although some reports suggest an association of Kava Kava with hepatotoxicity ,
      it continues to be used in the United States due to lack of toxicity
      characterization. In these studies F344/N rats and B6C3F1 mice were administered
      Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or
      two years. Results from prechronic studies administered Kava Kava at 0.125 to
      2g/kg body weight revealed dose-related increases in liver weights and incidences
      of hepatocellular hypertrophy. In the chronic studies, there were dose-related
      increases in the incidences of hepatocellular hypertrophy in rats and mice
      administered Kava Kava for up to 1g/kg body weight. This was accompanied by
      significant increases in incidences of centrilobular fatty change. There was no
      treatment- related increase in carcinogenic activity in the livers of male or
      female rats in the chronic studies. Male mice showed a significant dose-related
      increase in the incidence of hepatoblastomas. In female mice, there was a
      significant increase in the combined incidence of hepatocellular adenoma and
      carcinoma in the low and mid dose groups but not in the high dose group. These
      findings were accompanied by several nonneoplastic hepatic lesions.

PMID- 21871524
TI  - Implication of an Asp residue in the ribonucleolytic activity of hirsutellin A
      reveals new electrostatic interactions at the active site of ribotoxins.
AB  - Ribotoxins are fungal extracellular ribonucleases that specifically cleave
      ribosomes leading to cell-death via apoptosis. alpha-Sarcin is the ribotoxin
      studied in deepest detail, and therefore constitutes the referential protein for
      the whole family. It has been demonstrated that ribotoxin activity depends on a
      very precise structural microenvironment in which electrostatic interactions
      among residues in the active site are of the highest importance. Hirsutellin A
      (HtA) has been recently described as the smallest ribotoxin known to date,
      encompassing all the abilities of previously characterized members of this family
      into a shorter sequence. Comparison of HtA and alpha-sarcin three-dimensional
      structures suggested that residues presumably forming the catalytic triad of HtA
      would be His 42, Glu 66, and His 113. Within this same idea, the presence of an
      Asp residue (Asp 40) in a position equivalent to alpha-sarcin Tyr 48 is
      highlighted as a novelty in this field. In this work, substitution mutants H42Q,
      E66Q and H113Q, as well as double and triple mutants in all possible
      combinations, are studied regarding their ribonucleolytic activity and
      cytotoxicity. Implication of these three residues in the ribotoxin activity of
      HtA is confirmed, though none of them is strictly essential for ribosomal
      cleavage. Studies with mutants D40N and D40N/E66Q demonstrate an important role
      for Asp 40 in the activity of HtA and establish a new set of electrostatic
      interactions different from the one described for already known ribotoxins.

PMID- 21871525
TI  - Platelet type III collagen binding protein (TIIICBP) presents high biochemical
      and functional similarities with kindlin-3.
AB  - Type III collagen binding protein (TIIICBP) was previously described as a
      platelet membrane protein that recognizes the KOGEOGPK peptide sequence within
      type III collagen. In order to better characterize this protein, we performed
      different approaches including mass spectrometry sequencing and functional
      experiments. This study leads to identify high biochemical and functional
      similarities between TIIICBP and kindlin-3, a member of a family of focal
      adhesion proteins. Indeed, mass spectrometry surveys indicated that TIIICBP
      contains several peptides identical to kindlin-3, covering 41% of the amino acid
      sequence. Polyclonal antibodies raised against a kindlin-3 specific N-terminal
      sequence, recognized and immunoprecipitated TIIICBP from platelet lysates.
      Electron microscopy and flow cytometry experiments showed that kindlin-3, as well
      as TIIICBP, were present associated to platelet membrane and a translocation of
      cytosolic kindlin-3 to the platelet membrane was observed after platelet
      activation. Similarly to anti-TIIICBP antibodies and the KOGEOGPK peptide, anti
      kindlin-3 antibodies inhibited platelet interactions with type III collagen under
      flow conditions and slowed down platelet aggregation induced by glycoprotein VI
      agonists; e.g. collagen-related peptides and convulxin. In addition, the anti
      kindlin-3 antibody inhibited platelet aggregation induced by low - but not high -
      doses of ADP or thrombin which depends on alpha(IIb)beta(3) integrin function. In
      conclusion, our results show that the peptides identified by mass spectrometry
      from purified TIIICBP correspond to the kindlin-3 protein and demonstrate
      biochemical and functional similarities between TIIICBP and kindlin-3,
      strengthening a key role for TIIICBP/kindlin-3 in platelet interactions with
      collagen by cooperating with glycoprotein VI activation and integrin clustering
      in focal adhesion complexes.

PMID- 21871526
TI  - Tissue- and cell-specific functions of the androgen receptor revealed through
      conditional knockout models in mice.
AB  - This review aims to evaluate the contribution of individual cell-selective
      knockout models to our current understanding of androgen action. Cre/loxP
      technology has allowed the generation of cell-selective knockout models targeting
      the androgen receptor (AR) in distinct putative target cells in a wide variety of
      organs and tissues including: testis, ovary, accessory sex tissues, muscle, bone,
      fat, liver, skin and myeloid tissue. In some androgen-regulated processes such as
      spermatogenesis and folliculogenesis this approach has lead to the identification
      of a key cellular mediator of androgen action (Sertoli and granulosa cells,
      respectively). In many target tissues, however, the final response to androgens
      appears to be more complex. Here, cell-selective knockout technology offers a
      platform upon which we can begin to unravel the more complex interplay and
      signaling pathways of androgens. A prototypic example is the analysis of
      mesenchymal-epithelial interactions in many accessory sex glands. Furthermore,
      for some actions of testosterone, in which part of the effect is mediated by the
      active metabolite 17beta-estradiol, conditional knockout technology offers a
      novel strategy to study the relative contribution of AR and estrogen receptor
      mediated signaling. The latter approach has already resulted in a better
      understanding of androgen action in brain and bone. Finally, cell-selective
      knockout technology has generated valuable models to search for AR-controlled
      molecular mediators of androgen action, a strategy that has successfully been
      applied to the study of androgen action in the testis and in the epididymis.
      Although some conditional knockout models have provided clear answers to
      physiologic questions, it should be noted that others have pointed to unexpected
      complexities or technical limitations confounding interpretation of the results.

PMID- 21871527
TI  - Androgen receptor coregulators: recruitment via the coactivator binding groove.
AB  - Androgens are key regulators of male sexual differentiation and essential for
      development and maintenance of male reproductive tissues. The androgens
      testosterone and dihydrotestosterone mediate their effect by binding to, and
      activation of the androgen receptor (AR). Upon activation, the AR is able to
      recognize specific DNA sequences in gene promoters and enhancers from where it
      recruits coregulators to orchestrate chromatin remodeling and transcription
      regulation. The number of proteins that bind to the AR has surpassed 200 and many
      of them enhance (coactivator) or repress (corepressor) its transactivating
      capacity. For most of these coregulators, their AR binding interface and their
      exact mode of action still needs to be elucidated, but for some of the more
      classical coactivators and corepressors, we gained insight in their working
      mechanisms. Of particular interest are specific sequences (LxxLL and FxxLF-like
      motifs) in a subset of coactivators that interact with the AR via a coactivator
      binding groove in the ligand-binding domain. As compared to other steroid
      receptors, the conformation of the AR coactivator binding pocket is unique and
      preferentially binds FxxLF-like motifs. This predisposition is expected to
      contribute to the regulation of specific sets of target genes via recruitment of
      selected coregulators. This review provides an overview of these (inter)actions
      with a focus on the unique characteristics of the AR coactivator binding groove.

PMID- 21871528
TI  - What is in a name?

PMID- 21871529
TI  - Molecular biology of androgen insensitivity.
AB  - Androgen insensitivity syndrome (AIS) is the most common specific cause of 46,XY
      disorder in sex development. The androgen signaling pathway is complex but so
      far, the only gene linked with AIS is the androgen receptor (AR). Mutations in
      the AR are found in most subjects with complete AIS but in partial AIS, the rate
      has varied 28-73%, depending on the case selection. More than 400 different
      mutations in AR leading to AIS have been reported. Most mutations are missense
      substitutions located in the ligand binding domain of the receptor. However, when
      systematically screened, a substantial amount of mutations can be detected also
      in the N-terminal domain encoded by exon 1. Within this exon lie two
      trinucleotide, CAG and GGN repeat regions which are polymorphic in length. Their
      role in androgen insensitivity is somewhat unclear. Recent advances in protein
      modeling have resulted in better understanding of the mechanism of known AR
      mutations.

PMID- 21871530
TI  - Effects of cholinergic system of dorsal hippocampus of rats on MK-801 induced
      anxiolytic-like behavior.
AB  - RATIONALE: Some investigations have shown that the glutamate receptors play a
      critical role in cognitive processes such as learning and anxiety. OBJECTIVES:
      The possible involvement of the cholinergic system of the dorsal hippocampus in
      the anxiolytic-like response induced by MK-801, NMDA receptor antagonist, was
      investigated in the present study. METHODS: Male Wistar rats were used in the
      elevated plus maze apparatus to test the parameters: open arm time (%OAT), open
      arm entries (%OAE), close arm time (%CAT), close arm entries (%CAE) and other
      exploratory behaviors (locomotor activity, grooming, rearing and defecation) of
      anxiety-like response. RESULTS: The data indicated that intra-CA1 administration
      of MK-801 increased %OAT (2MUg/rat) and %OAE (1 and 2MUg/rat) while decreased
      %CAT and %CAE and did not alter other exploratory behaviors, indicating an
      anxiolytic-like effect. Moreover, intra-hippocampal injections of mecamylamine, a
      cholinergic receptor antagonists (2MUg/rat) and scopolamine (4MUg/rat), by
      themselves, 5min before testing, increased %OAT and %OAE but decreased %CAT and
      %CAE and did not alter locomotor activity and other exploratory behaviors,
      suggesting an anxiolytic-like effect. On the other hand, intra-CA1 co
      administration of an ineffective dose of scopolamine (3MUg/rat), but not
      mecamylamine (1MUg/rat), with an ineffective dose of MK-801 (0.5MUg/rat)
      increased %OAT and %OAE and decreased %CAT and %CAE. The data may indicate the
      possible involvement of the cholinergic system of the CA1 in the anxiolytic-like
      response induced by MK-801.

PMID- 21871531
TI  - Evaluation of brain pharmacokinetics of (+)MK-801 in relation to behaviour.
AB  - The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist (+)MK-801 is
      widely used in animal research (over 3000 publications), however its
      extracellular brain concentration has never been reported. Here, we show using in
      vivo microdialysis that systemic injection of (+)MK-801 at doses of 0.05, 0.1 or
      0.2mg/kg resulted in peak brain ECF concentration of 6, 14 or 34 nM,
      respectively. Moreover, (+)MK-801 resulted in a dose-dependent learning
      impairment in the Morris water maze as well as hyperactivity in the open field.
      These data demonstrate for the first time that (+)MK-801 at doses producing
      behavioural alterations expected from NMDA receptor blockade reaches
      extracellular brain concentrations corresponding to the affinity at NMDA
      receptors.

PMID- 21871532
TI  - 5-HTTLPR genotype and gender, but not chronic fluoxetine administration, are
      associated with cortical TREK1 protein expression in rhesus macaques.
AB  - TREK1 is a widely expressed background potassium channel. Similar to mice treated
      with selective serotonin reuptake inhibitors (SSRIs), TREK1 knockout mice are
      resistant to depression-like behavior and have elevated serotonin levels leading
      to speculation that TREK1 inhibition may contribute to the therapeutic effects of
      SSRIs. This study examined how chronic fluoxetine administration and a common
      functional polymorphism in the serotonin-transporter-linked promoter region (5
      HTTLPR) influence cortical TREK1 expression in 24 rhesus monkeys. The short rh5
      HTTLPR allele as well as female gender were associated with reduced cortical
      TREK1 protein expression but chronic SSRI administration had no effect. These
      results suggest that serotonin may influence TREK1, but that chronic SSRI
      treatment does not result in long lasting changes in cortical TREK1 protein
      expression. TREK1 gender differences may be related to gender differences in
      serotonin and require further research.

PMID- 21871533
TI  - Neural activation during imitation of movements presented from four different
      perspectives: a functional magnetic resonance imaging study.
AB  - The present study examined the effects of the perspective of movement presented
      for imitation in healthy volunteers, using functional magnetic resonance imaging
      (fMRI) to assess the magnitude and distribution of elicited brain activity. We
      sought to identify the pattern of brain activity associated with the performance
      of finger imitation tasks under four different imitation conditions. Video
      presentations of a hand and forearm performing random sequential contact between
      different fingers and the thumb were presented for imitation, while fMRI was
      recorded. The four types of model for imitation were: a hand and forearm pointing
      away from the subject, as if the subject were looking at their own limb (first
      person perspective), from both anatomical (a right hand to be imitated by the
      subject's own right hand) and specular (a mirror image or "left" hand to be
      imitated by the subject's right hand) perspectives; and a hand/forearm pointing
      toward the subject, as if it was the hand of another person facing the subject
      (third-person perspective), from both anatomical (the opposite person's right
      hand) and specular (the opposite person's left hand) perspectives. In addition,
      participants completed a motor control task. The results revealed a significant
      difference in the magnitude of brain activation between the first- and third
      person perspective conditions, suggesting that subjects used the first-person
      imitation model as a substitute for internal self-representation, thus requiring
      less effort. The first-person perspective anatomical model activated only the
      right posterior insula, recruiting significantly fewer brain regions than the
      other model types, compared with the control condition. These findings suggest
      that first-person anatomical perspective models may be optimal for ease of
      imitation in motor learning.

PMID- 21871534
TI  - A preliminary study of the dysregulation of the resting networks in first-episode
      medication-naive adolescent depression.
AB  - Recent developments in depression studies have heightened the need for
      investigating adolescent major depressive disorder (MDD). Many previous
      neuroimaging studies used task designs and found consistent results in the
      dysfunction of brain regions in depressed adolescent patients. In this study, we
      aimed to evaluate the topological properties of brain functional networks of
      adolescents with MDD from an integrated view. Using resting state functional
      magnetic resonance imaging (fMRI), graph theory was applied to construct the
      resting networks in 16 first-episode and unmedicated adolescents with MDD and 16
      healthy controls (HC). Our results showed that the topological properties of
      depressed adolescents' networks were significantly disrupted compared with HC.
      Dysregulation of brain regions were found in the anterior cingulate cortex,
      dorsolateral, medial and inferior prefrontal cortex, insula, amygdala, and the
      temporal cortices. Furthermore, the connectivity degree of amygdala related
      functional connection was positively correlated with the duration of depression.
      Detection and estimation of these functional impairments may advance our current
      understanding of the pathophysiological mechanism of adolescent MDD.

PMID- 21871535
TI  - Long distance running and acute effects on plantar foot sensitivity and plantar
      foot loading.
AB  - The plantar surface of the foot senses local pressures during stance and
      locomotion. These foot loading characteristics may be affected by long distance
      running. Little is known about the physiological effects of sports-related
      loading on plantar sensitivity and their relationship with plantar foot loading.
      The purpose of this study was to investigate the acute effects of long distance
      running on plantar sensitivity to touch and their relationship with foot loading
      characteristics. It was hypothesized that plantar sensation would decrease after
      long distance running and may be related to foot loading characteristics. In 15
      middle-aged runners, sensory detection thresholds to light touch and plantar
      pressures were measured before and after a 10 km run. After the run, no
      significant changes in sensory perception thresholds were observed so that
      correlations between foot sensitivity and foot loading could not be calculated. A
      significant decrease of force-time integrals and maximum forces was demonstrated
      in the whole foot (-6.2%, p=0.003; -3.9%, p=0.001) and the heel (-10.5%, p=0.003;
      -8.5%, p=0.002). Furthermore, maximum force was significantly reduced in the
      lateral midfoot (-6.4%, p=0.002). In conclusion, a sub-maximal 10 km running
      exercise appears to have no significant acute effects on plantar sensitivity,
      plantar pressure distribution and peak forces.

PMID- 21871536
TI  - Stachybotrys microspora triprenyl phenol-7, a novel fibrinolytic agent,
      suppresses superoxide production, matrix metalloproteinase-9 expression, and
      thereby attenuates ischemia/reperfusion injury in rat brain.
AB  - Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a novel fibrinolytic agent
      with anti-inflammatory effect. Previous study demonstrated that SMTP-7 further
      ameliorated infarction volume in a mouse embolic stroke model compared with
      tissue type plasminogen activator (tPA), but the reason SMTP-7 has more
      beneficial effect than tPA has not yet been determined. In the present study, we
      investigated whether SMTP-7 has an intrinsic neuroprotective effect against
      transient focal cerebral ischemia (tFCI). Sprague-Dawley rats were subjected to
      tFCI by intraluminal middle cerebral artery occlusion for 2h. Following induction
      of tFCI, rats were randomized into two groups based on the agent administered:
      SMTP-7 group and vehicle group. We examined cerebral infarction volume 24h after
      reperfusion, and evaluated superoxide production, the expressions of
      nitrotyrosine and matrix metalloproteinase-9 (MMP-9), which play major roles in
      secondary brain injury and hemorrhagic transformation. The findings showed that
      SMTP-7 significantly suppressed superoxide production, the expression of
      nitrotyrosine and MMP-9 after tFCI, and consequently attenuated ischemic neuronal
      damage. These results suggest that SMTP-7 has an intrinsic neuroprotective effect
      on ischemia/reperfusion injury through the suppression of oxidative stress and
      MMP-9 activation.

PMID- 21871537
TI  - Effect of bitter compounds on amylase secretion in murine submandibular glands:
      Signaling pathway mechanisms.
AB  - BACKGROUND: Amylase is synthesized in submandibular glands (SMG) and released
      into the oral cavity to degrade carbohydrates in the mouth. Bitter taste
      receptors (T2R) belong to the G-protein coupled receptor (GPCR) family and are
      expressed in the taste cells and also in the digestive tract. METHODS: The
      activity of amylase secreted by murine SMG was measured, detecting maltose by
      Bernfeld's method. Amylase and T2R6 were detected by imunohistochemistry and
      Western blot. The expression of Ggustducin, Gi, and phospholipase Cbeta2 was also
      studied by Western blot. cAMP levels were measured by radioimmunoassay and
      inositol monophosphate production was quantified by ELISA. RESULTS: Theophylline,
      denatonium and cycloheximide exerted a dose-dependent inhibition on amylase
      secretion. This effect was reverted by preincubating SMG with an anti-Galphai
      antibody. cAMP production was increased by the same compounds, an effect that was
      also abrogated by an anti-Galphai antibody. Bitter compounds reduced inositol
      monophosphate formation in SMG and H-89, a protein kinase A inhibitor, reverted
      this action, revealing that this protein kinase down regulates phospholipase C
      activity. GENERAL SIGNIFICANCE: We demonstrated that theophylline, denatonium and
      cycloheximide inhibit salivary amylase secretion, activating an intracellular
      signaling pathway that involves cAMP and phospholipase C, that cross talks via
      protein kinase A.

PMID- 21871538
TI  - A mitochondrial etiology of Alzheimer and Parkinson disease.
AB  - BACKGROUND: The genetics and pathophysiology of Alzheimer Disease (AD) and
      Parkinson Disease (PD) appears complex. However, mitochondrial dysfunction is a
      common observation in these and other neurodegenerative diseases. SCOPE OF
      REVIEW: We argue that the available data on AD and PD can be incorporated into a
      single integrated paradigm based on mitochondrial genetics and pathophysiology.
      MAJOR CONCLUSIONS: Rare chromosomal cases of AD and PD can be interpreted as
      affecting mitochondrial function, quality control, and mitochondrial DNA (mtDNA)
      integrity. mtDNA lineages, haplogroups, such haplogroup H5a which harbors the
      mtDNA tRNA(Gln) A8336G variant, are important risk factors for AD and PD. Somatic
      mtDNA mutations are elevated in AD, PD, and Down Syndrome and Dementia (DSAD)
      both in brains and also systemically. AD, DS, and DSAD brains also have reduced
      mtDNA ND6 mRNA levels, altered mtDNA copy number, and perturbed Abeta metabolism.
      Classical AD genetic changes incorporated into the 3XTg-AD (APP, Tau, PS1) mouse
      result in reduced forebrain size, life-long reduced mitochondrial respiration in
      3XTg-AD males, and initially elevated respiration and complex I and IV activities
      in 3XTg-AD females which markedly declines with age. GENERAL SIGNIFICANCE:
      Therefore, mitochondrial dysfunction provides a unifying genetic and
      pathophysiology explanation for AD, PD, and other neurodegenerative diseases.
      This article is part of a Special Issue entitled Biochemistry of Mitochondria.

PMID- 21871540
TI  - Potent suppression of stretch reflex activity after systemic or spinal delivery
      of tizanidine in rats with spinal ischemia-induced chronic spastic paraplegia.
AB  - BACKGROUND: Spasticity and rigidity are serious complications associated with
      spinal traumatic or ischemic injury. Clinical studies show that tizanidine (Tiz)
      is an effective antispasticity agent; however, the mechanism of this effect is
      still not clear. Tiz binds not only to alpha2-adrenoreceptors (AR) but also to
      imidazoline (I) receptors. Both receptor systems (AR+I) are present in the spinal
      cord interneurons and alpha-motoneurons. The aim of the present study was to
      evaluate the therapeutic potency of systematically or spinally (intrathecally
      [IT]) delivered Tiz on stretch reflex activity (SRA) in animals with ischemic
      spasticity, and to delineate supraspinal or spinal sites of Tiz action.
      EXPERIMENTAL PROCEDURES: Animals were exposed to 10 min of spinal ischemia to
      induce an increase in SRA. Increase in SRA was identified by simultaneous
      increase in recorded electromyography (EMG) activity and ankle resistance
      measured during computer-controlled ankle dorsiflexion (40 degrees /3 s) in fully
      awake animals. Animals with increased SRA were divided into several experimental
      subgroups and treated as follows: (i) Tiz administered systemically at the dose
      of 1 mg kg(-1), or IT at 10 MUg or 50 MUg delivered as a single dose; (ii)
      treatment with systemic Tiz was followed by the systemic injection of vehicle, or
      by nonselective AR antagonist without affinity for I receptors; yohimbine (Yoh),
      alpha2A AR antagonist; BRL44408 (BRL), alpha2B AR antagonist; ARC239 (ARC),
      nonselective AR and I(1) receptor antagonist; efaroxan (Efa), or nonselective AR
      and I(2) receptor antagonist; idazoxan (Ida); (iii) treatment with IT Tiz was
      followed by the IT injection of selective alpha2A AR antagonist; atipamezole
      (Ati). In a separate group of spastic animals the effect of systemic Tiz
      treatment (1 mg/kg) or isoflurane anesthesia on H-reflex activity was also
      studied. RESULTS: Systemic and/or IT treatment with Tiz significantly suppressed
      SRA. This Tiz-mediated anti-SRA effect was reversed by BRL (5 mg kg(-1)), Efa (1
      mg kg(-1)), and Ida (1 mg kg(-1)). No reversal was seen after Yoh (3 mg kg(-1))
      or ARC (5 mg kg(-1)) treatment. Anti-SRA induced by IT Tiz (50 MUg) was reversed
      by IT injection of Ati (50 MUg). Significant suppression of H-reflex was measured
      after systemic Tiz treatment (1 mg/kg) or isoflurane (2%) anesthesia,
      respectively. Immunofluorescence staining of spinal cord sections taken from
      animals with spasticity showed upregulation of alpha2A receptor in activated
      astrocytes. CONCLUSIONS: These data suggest that alpha2A AR and I receptors, but
      not alpha2B AR, primarily mediate the Tiz-induced antispasticity effect. This
      effect involves spinal and potentially supraspinal sites and likely targets
      alpha2A receptor present on spinal neurons, primary afferents, and activated
      astrocytes. Further studies using highly selective antagonists are needed to
      elucidate the involvement of specific subtypes of the AR and I receptors in the
      antispasticity effect seen after Tiz treatment.

PMID- 21871541
TI  - Glial cell-line derived neurotrophic factor is essential for electroconvulsive
      shock-induced neuroprotection in an animal model of Parkinson's disease.
AB  - Sustained motor improvement in human patients with idiopathic Parkinson's disease
      has been described following electroconvulsive shock (ECS) treatment. In rats,
      ECS stimulates the expression of various trophic factors (TFs), some of which
      have been proposed to exert neuroprotective actions. We previously reported that
      ECS protects the integrity of the rat nigrostriatal dopaminergic system against 6
      hydroxydopamine (6-OHDA)-induced toxicity; in order to shed light into its
      neuroprotective mechanism, we studied glial cell-line derived neurotrophic factor
      (GDNF) levels (the most efficient TF for dopaminergic neurons) in the substantia
      nigra (SN) and striatum of 6-OHDA-injected animals with or without ECS treatment.
      6-OHDA injection decreased GDNF levels in the SN control animals, but not in
      those receiving chronic ECS, suggesting that changes in GDNF expression may
      participate in the ECS neuroprotective mechanism. To evaluate this possibility,
      we inhibit GDNF by infusion of GDNF function blocking antibodies in the SN of 6
      OHDA-injected animals treated with ECS (or sham ECS). Animals were sacrificed 7
      days after 6-OHDA infusion, and the integrity of the nigrostriatal system was
      studied by tyrosine hydroxylase immunohistochemistry and Cresyl Violet staining.
      Neuroprotection observed in ECS-treated animals was inhibited by GDNF antibodies
      in the SN. These results robustly demonstrate that GDNF is essential for the ECS
      neuroprotective effect observed in 6-OHDA-injected animals.

PMID- 21871539
TI  - Cannabinoid receptor involvement in stress-induced cocaine reinstatement:
      potential interaction with noradrenergic pathways.
AB  - This study examined the role of endocannabinoid signaling in stress-induced
      reinstatement of cocaine seeking and explored the interaction between
      noradrenergic and endocannabinergic systems in the process. A well-validated
      preclinical model for human relapse, the rodent conditioned place preference
      assay, was used. Cocaine-induced place preference was established in C57BL/6 mice
      using injections of 15 mg/kg cocaine. Following extinction of preference for the
      cocaine-paired environment, reinstatement of place preference was determined
      following 6 min of swim stress or cocaine injection (15 mg/kg, i.p.). The role of
      endocannabinoid signaling was studied using the cannabinoid antagonist AM-251 (3
      mg/kg, i.p.). Another cohort of mice was tested for reinstatement following
      administration of the cannabinoid agonist CP 55,940 (10, 20, or 40 MUg/kg, i.p.).
      The alpha-2 adrenergic antagonist BRL-44408 (5 mg/kg, i.p.) with or without CP
      55,940 (20 MUg/kg) was administered to a third group of mice. We found that: (1)
      AM-251 blocked forced swim-induced, but not cocaine-induced, reinstatement of
      cocaine-seeking behavior; (2) the cannabinoid agonist CP 55,940 did not reinstate
      cocaine-seeking behavior when administered alone but did synergize with a non
      reinstating dose of the alpha-2 adrenergic antagonist BRL-44408 to cause
      reinstatement. These results are consistent with the hypothesis that stress
      exposure triggers the endogenous activation of CB1 receptors and that activation
      of the endocannabinoid system is required for the stress-induced relapse of the
      mice to cocaine seeking. Further, the data suggest that the endocannabinoid
      system interacts with noradrenergic mechanisms to influence stress-induced
      reinstatement of cocaine-seeking behavior.

PMID- 21871542
TI  - Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus
      var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme
      inhibition.
AB  - The in vivo and in vitro mechanistic anti-inflammatory actions of cucurbitacin E
      (CE) (Citrullus lanatus var. citroides) were examined. The results showed that
      LPS/INF-gamma increased NO production in RAW264.7 macrophages, whereas L-NAME and
      CE curtailed it. CE did not reveal any cytotoxicity on RAW264.7 and WRL-68 cells.
      CE inhibited both COX enzymes with more selectivity toward COX-2. Intraperitoneal
      injection of CE significantly suppressed carrageenan-induced rat's paw edema.
      ORAC and FRAP assays showed that CE is not a potent ROS scavenger. It could be
      concluded that CE is potentially useful in treating inflammation through the
      inhibition of COX and RNS but not ROS.

PMID- 21871543
TI  - Role of stimulus-stimulus pairing in matching-to-sample procedure: cross-species
      comparison of humans and pigeons.
AB  - The present experiment examined whether, in a matching-to-sample (MTS) procedure,
      a relation between two stimuli, a sample and a comparison, could be established
      as a result of just stimulus-stimulus pairing, even if back up reinforcers were
      never provided for the conditional relation between the sample and comparison
      stimuli, but rather only for the comparison stimulus. A procedure called "pseudo
      matching-to-sample" was used in which, when S1 was presented as a sample
      stimulus, two comparison stimuli (C1 and C2) were presented, and only responses
      to C1 were reinforced. Conversely, when S2 was presented, only responses to C3
      (and not C4) were reinforced. In other words, organisms experiencing this
      procedure could discriminate C1 from C2, and C3 from C4, by simple discrimination
      without regard to the conditional sample stimuli. In order to examine cross
      species differences, responding by humans in this procedure was compared to that
      by pigeons. Although the humans developed a discriminative function for the
      sample stimuli, that is, the humans' responding was affected by both the sample
      stimuli and the reinforcers, responding by the pigeons was affected solely by the
      reinforcers. These data suggest that, in this procedure, humans (but not pigeons)
      are able to learn relations among stimuli simply as a result of stimulus-stimulus
      pairing.

PMID- 21871545
TI  - Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach
      for in vitro cytotoxicity screening of lysine-based surfactants with potential
      pharmaceutical applications.
AB  - Surfactants are used as additives in topical pharmaceuticals and drug delivery
      systems. The biocompatibility of amino acid-based surfactants makes them highly
      suitable for use in these fields, but tests are needed to evaluate their
      potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and
      non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine
      based surfactants by means of two in vitro endpoints (MTT and NRU). This
      comparative assay may serve as a reliable approach for predictive toxicity
      screening of chemicals prior to pharmaceutical applications. After 24-h of cell
      exposure to surfactants, differing toxic responses were observed. NCTC 2544 and
      3T6 cell lines were the most sensitive, while both tumor cells and 3T3
      fibroblasts were more resistant to the cytotoxic effects of surfactants. IC(50)
      values revealed that cytotoxicity was detected earlier by MTT assay than by NRU
      assay, regardless of the compound or cell line. The overall results showed that
      surfactants with organic counterions were less cytotoxic than those with
      inorganic counterions. Our findings highlight the relevance of the correct choice
      and combination of cell lines and bioassays in toxicity studies for a safe and
      reliable screen of chemicals with potential interest in pharmaceutical industry.

PMID- 21871544
TI  - An approach for rapid development of nasal delivery of analgesics--identification
      of relevant features, in vitro screening and in vivo verification.
AB  - Drug delivery via the nasal route is gaining increasing interest over the last
      two decades as an alternative to oral or parenteral drug administration. In the
      current study an approach for rapid identification of relevant features,
      screening and in vivo verification of potential therapeutic agents for nasal
      delivery was carried out using "analgesic agents" as an example. Four such drug
      candidates (rizatriptan, meloxicam, lornoxicam and nebivolol) were initially
      identified as potentially viable agents based on their therapeutic use and
      physicochemical characteristics. An in vitro screening was then carried out using
      the Calu-3 cell line model. Based on the in vitro screening results and the
      reported pharmacokinetic and the stability data, meloxicam was predicted to be
      the most promising drug candidate and was subsequently verified using an in vivo
      animal model. The in vivo results showed that nasal administration of meloxicam
      was comparable to its intravenous administration, with respect to plasma drug
      concentration and AUC(0-2h). In addition, nasal absorption of meloxicam was much
      more rapid with higher plasma drug concentration and AUC(0-2h) than that of oral
      administration. The current approach appears to be capable of developing
      "analgesic agents" suitable for nasal delivery. Further studies are needed to
      prove the clinical advantage of the specific selected agent, meloxicam, by nasal
      administration in patients.

PMID- 21871546
TI  - Interplay of formulation and process methodology on the extent of nifedipine
      molecular dispersion in polymers.
AB  - The aim of this study is to evaluate effects of formulation and process
      technology on drug molecular dispersibility in solid dispersions (SDs).
      Nifedipine solid dispersions with ethylcellulose (EC) and/or Eudragit RL (RL)
      prepared by co-precipitation, co-evaporation, and fusion methods were
      characterized with FTIR, DSC, and XRPD for the content of nifedipine as molecular
      dispersion, amorphous and/or crystalline suspensions. A method was developed
      based on regular solution and Flory-Huggins theories to calculate drug-polymer
      interaction parameter in solid dispersion systems. A synergic effect of RL and EC
      on nifedipine molecular dispersibility in solid dispersions was observed.
      Increasing RL/EC ratio resulted in a higher degree of drug-polymer interaction
      that thermodynamically favored molecular dispersion, which, however, was
      counteracted by a corresponding decrease in the matrix glass transition point
      that kinetically favored phase-separation. Process methodology was found to play
      an important role in the formation of amorphous SD. The ranking of technologies
      with respect to the extent of molecular dispersion from high to low is fusion>co
      evaporation>co-precipitation, wherein the solidification rate of polymeric
      solution and non-solvent effects were linked to kinetic entrapment of drug
      molecules in polymeric networks. Since nifedipine molecular dispersibility in
      EC/RL polymer(s) is a result of interplay between thermodynamic and kinetic
      factors, nifedipine molecular dispersions prepared for this study are
      thermodynamically metastable systems. To explore those supersaturation systems
      for use in drug delivery of poorly water soluble drugs, it is critical to balance
      drug-polymer interactions and matrix glass transition point and to consider a
      process technology with a fast solidification rate during formulation and process
      development of amorphous SD.

PMID- 21871547
TI  - Production and characterization of antioxidant apigenin nanocrystals as a novel
      UV skin protective formulation.
AB  - Flavonoids have many positive effects on various cell layers of the skin (e.g.
      anti-oxidant, anti-allergic and anti-inflammatory effects). However, the limiting
      factor of the use of flavonoids is their low water solubility. To overcome the
      poor solubility, apigenin nanosuspensions were prepared using the combination
      technology (CT), i.e. bead milling and subsequently high pressure homogenization.
      Distinct reduction in particle size was observed after each bead milling passage
      resulting in z-average (PCS) of 413 nm and a polydispersity index of 0.202. The
      LD data showed a similar pattern of particle size reduction reaching a diameter
      99% (d(v)99%) of 0.515 MUm. The antioxidant capacity of apigenin nanocrystals
      were almost doubled compared to the original coarse suspension. The developed
      smartCrystals can be easily incorporated into gels, which makes apigenin
      nanocrystals available for dermal application as efficient antioxidant.

PMID- 21871548
TI  - An inventory of the ethnobotanicals used as anti-diabetic by a rural community of
      Dhemaji district of Assam, Northeast India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional remedies used for treating diabetic
      ailments are very important in the primary health care of the people living in
      rural Dhemaji district of Assam, north-east India. Novel information gathered
      from the current survey is important in preserving folk indigenous knowledge.
      MATERIALS AND METHODS: Interviews were conducted amongst 80 households comprising
      of 240 individuals using semi-structured questionnaires. The focus was on plants
      used in treating diabetes mellitus. RESULTS: The current survey documented 21
      plant species (20 families) which are reportedly used to treat diabetes mellitus
      by the rural people in the study area. To the best of our knowledge, Amomum
      linguiforme, Cinnamomum impressinervium, Colocasia esculenta, Dillenia indica,
      Euphorbia ligularia, Garcinia pedunculata, Solanum indicum, Sterculia villosa and
      Tabernaemontana divaricata are recorded for the first time based on globally
      published literature as medicinal plants used for treating diabetes mellitus and
      related symptoms. CONCLUSIONS: The wide variety of plants that are used to treat
      diabetes mellitus in this area supports the traditional value that medicinal
      plants have in the primary health care system of the rural people of Dhemaji
      district of Assam. The finding of new plant uses in the current study reveals the
      importance of the documentation of such ethnobotanical knowledge.

PMID- 21871549
TI  - Khat (Catha edulis) and ethanol co-dependence modulate seizure expression in a
      pentylenetetrazol seizure model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Khat is a plant with psychostimulant properties
      whose parts, mainly leaves and twigs, are chewed for its euphoriant effects. Khat
      use and ethanol abuse are increasingly becoming global health concerns especially
      among many disadvantaged social groups. The present studies were undertaken to
      investigate seizure susceptibility and responses following chronic co
      administration of khat and ethanol. MATERIALS AND METHODS: Juvenile male Sprague
      Dawley (SD) rats were administered khat, ethanol or combined khat and ethanol
      twice daily for 28 days by gavage. Khat-treated animals received 2 g/kg or 4 g/kg
      body weight continuously for the study period. Ethanol-treated animals received
      20% ethanol at a dose of 4 g/kg body weight. The convulsant, pentylenetetrazol
      (PTZ), was administered intraperitoneally at a dose of 40 mg/kg body weight.
      Seizure responses were recorded. RESULTS: Twice-daily dosing of khat did not
      produce inhibition of weight gain. Khat alone, combined khat and 20% ethanol, but
      not 20% ethanol alone, significantly reduced the latency to seize. Khat treatment
      at 2 g/kg but not 4 g/kg body weight also significantly increased the duration of
      seizures. Conversely, combined khat and ethanol reduced the duration of seizures
      compared to controls. Ethanol alone reduced the seizure severity while khat
      alone, and combined khat and ethanol, produced close to the maximum seizure
      severity. CONCLUSIONS: These data suggest that combined moderate to high dose
      khat and ethanol co-dependence produce a greater deleterious CNS effect than
      either drug alone. Future studies will address neurochemical effects, in addition
      to neuroadaptations, resulting from coabuse of these drugs.

PMID- 21871550
TI  - Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle
      aged rats.
AB  - There is growing concern over the increasing instances of decline in cognitive
      abilities with aging in humans. The present study evaluated the benefits of the
      natural antioxidant, grape seed proanthocyanidin extract (GSPE) in treating the
      effects of age-related oxidative stress (OS) and accumulation of lipofuscin (LF)
      on the cognitive ability in rats. Female Wistar rats of 3- and 12-months of age
      received a daily oral supplement of GSPE until they attained 6- and 15-months of
      age. During this period, rats were tested for their cognitive ability. At the end
      of this period, blood glucose and markers of OS were assessed in the hippocampus.
      GSPE lowered blood glucose, lipid peroxidation, hydrogen peroxide level, and
      increased protein sulphydryl (P-SH) content in the hippocampus. In addition, GSPE
      significantly improved cognitive performance in the two age groups. These results
      demonstrate that the extent of OS-related LF accumulation is reducible by GSPE.
      They also suggest a critical role for GSPE as a neuroprotectant in the
      hippocampus and in preventing cognitive loss with aging.

PMID- 21871551
TI  - A high throughput screening assay for determination of chronological lifespan of
      yeast.
AB  - A high throughput screening assay was developed based on the yeast chronological
      aging model and applied in evaluating several factors that mediate lifespan,
      including inoculum size, cellular state in nutrient-rich medium, and calorie
      level. Using our assay, we confirmed the previously reported genetic mimics of
      calorie restriction, including deletion of TOR1, SCH9 or RAS2. In contrast,
      deletion of SIR2 had longevity effect but seemed to produce only small beneficial
      effect on the response to calorie restriction. Overall, this new high throughput
      screening assay may facilitate identification of calorie restriction mimetics
      with a rapid and simple protocol, uncomplicated data analysis, and high
      sensitivity. In addition, the assay also provides quantifiable data including lag
      time, growth rate, doubling time, and survival percentage.

PMID- 21871553
TI  - Increase in Trx2/Prx3 redox system immunoreactivity in the spinal cord and
      hippocampus of aged dogs.
AB  - We previously reported that no distinct neuronal loss occurred in the aged dog
      spinal cord, although oxidative stress was increased in the aged dog spinal cord.
      Thioredoxin 2 (Trx2)/peroxiredoxin 3 (Prx3) redox system is a major route for
      removing H(2)O(2) in the central nervous system. In the present study, we
      compared the distribution and immunoreactivity of thioredoxin reductase 2
      (TrxR2), Trx2 and Prx3 and their protein levels in the spinal cord and
      hippocampus between the adult (2-3 years) and aged (10-12 years) dogs. The number
      of TrxR2-immunoreactive neurons was slightly increased; however, its
      immunoreactivity was significantly increased in the aged spinal cord compared to
      that in the adult spinal cord. On the other hand, the number and immunoreactivity
      of both Trx2- and Prx3-immunoreactive neurons were significantly increased in the
      spinal cord of the aged dog. Similarly, in the hippocampus of the aged dog,
      TrxR2, Trx2 and Prx3 immunoreactivity and protein levels were markedly increased
      compared to those in the adult dog. These results indicate that the increases of
      TrxR2, Trx2 and Prx3 immunoreactivity and their protein levels in the aged spinal
      cord and hippocampus may contribute to reducing neuronal damage against oxidative
      stresses during normal aging.

PMID- 21871554
TI  - Biotransformation studies using hairy root cultures - A review.
AB  - Agrobacterium rhizogenes induced hairy root cultures are entering into a new
      juncture of functional research in generating pharmaceutical lead compounds by
      bringing about chemical transformations aided through its inherent enzyme
      resources. Rational utilization of hairy root cultures as highly effective
      biotransformation systems has come into existence in the last twenty years
      involving a wide range of plant systems as well as exogenous substrates and
      diverse chemical reactions. To date, hairy root cultures are preferred over plant
      cell/callus and suspension cultures as biocatalyst due to their
      genetic/biochemical stability, hormone-autotrophy, multi-enzyme biosynthetic
      potential mimicking that of the parent plants and relatively low-cost cultural
      requirements. The resultant biotransformed molecules, that are difficult to make
      by synthetic organic chemistry, can unearth notable practical efficacies by
      acquiring improved physico-chemical properties, bioavailability, lower toxicity
      and broader therapeutic properties. The present review summarizes the overall
      reported advances made in the area of hairy root mediated biotransformation of
      exogenous substrates with regard to their reaction types, plant systems
      associated, bacterial strains/molecules involved and final product recovery.

PMID- 21871552
TI  - Design, recruitment, logistics, and data management of the GEHA (Genetics of
      Healthy Ageing) project.
AB  - In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was
      initiated with the aim of identifying genes involved in healthy ageing and
      longevity. The first step in the project was the recruitment of more than 2500
      pairs of siblings aged 90 years or more together with one younger control person
      from 15 areas in 11 European countries through a coordinated and standardised
      effort. A biological sample, preferably a blood sample, was collected from each
      participant, and basic physical and cognitive measures were obtained together
      with information about health, life style, and family composition. From 2004 to
      2008 a total of 2535 families comprising 5319 nonagenarian siblings were
      identified and included in the project. In addition, 2548 younger control persons
      aged 50-75 years were recruited. A total of 2249 complete trios with blood
      samples from at least two old siblings and the younger control were formed and
      are available for genetic analyses (e.g. linkage studies and genome-wide
      association studies). Mortality follow-up improves the possibility of identifying
      families with the most extreme longevity phenotypes. With a mean follow-up time
      of 3.7 years the number of families with all participating siblings aged 95 years
      or more has increased by a factor of 5 to 750 families compared to when
      interviews were conducted. Thus, the GEHA project represents a unique source in
      the search for genes related to healthy ageing and longevity.

PMID- 21871555
TI  - The PPAR-gamma agonist troglitazone antagonizes survival pathways induced by STAT
      3 in recombinant interferon-beta treated pancreatic cancer cells.
AB  - We have previously shown that cancer cells can protect themselves from apoptosis
      induced by type I interferons (IFNs) through a ras->MAPK-mediated pathway. In
      addition, since IFN-mediated signalling components STATs are controlled by PPAR
      gamma we studied the pharmacological interaction between recombinant IFN-beta and
      the PPAR-gamma agonist troglitazone (TGZ). This combination induced a synergistic
      effect on the growth inhibition of BxPC-3, a pancreatic cancer cell line, through
      the counteraction of the IFN-beta-induced activation of STAT-3, MAPK and AKT and
      the increase in the binding of both STAT-1 related complexes and PPAR-gamma with
      specific DNA responsive elements. The synergism on cell growth inhibition
      correlated with a cell cycle arrest in G0/G1 phase, secondary to a long-lasting
      increase of both p21 and p27 expressions. Blockade of MAPK activation and the
      effect on p21 and p27 expressions, induced by IFN-beta and TGZ combination, were
      due to the decreased activation of STAT-3 secondary to TGZ. IFN-beta alone also
      increased p21 and p27 expression through STAT-1 phosphorylation and this effect
      was attenuated by the concomitant activation of IFNbeta-induced STAT-3
      activation. The combination induced also an increase in autophagy and a decrease
      in anti-autophagic bcl-2/beclin-1 complex formation. This effect was mediated by
      the inactivation of the AKT->mTOR-dependent pathway. To the best of our knowledge
      this is the first evidence that PPAR-gamma activation can counteract STAT-3
      dependent escape pathways to IFN-beta-induced growth inhibition through cell
      cycle perturbation and increased autophagic death in pancreatic cancer cells.

PMID- 21871556
TI  - Fe- and Zn-induced inhibition of Cd uptake in human lung cell lines: speciation
      studies with H441 and A549 cells.
AB  - Cadmium transport was studied in human lung cell lines A549 and H441 as a
      function of inorganic metal speciation. A 2-fold higher equilibrium accumulation
      was obtained in the A549 cells, but a specific system of transport of high
      affinity and low capacity was characterized in both these cells. Exposure
      conditions optimizing [Cd2+] increased Cd uptake, but CdCln2-n species are also
      taken up. Studies on Cd-Ca reciprocal inhibition do not support a role for Ca
      pathways in Cd uptake. Nramp2 and Zip8 mRNAs were detected in both cell lines. Fe
      inhibited Cd uptake in the nitrate medium with an apparent at pH 5.5. NRAMP2 may
      contribute to Cd uptake but a major role is precluded since the overall process
      of accumulation was inhibited by acidic conditions. Zn and Mn inhibited Cd uptake
      with the following observations: (1) Similar apparent Ki values for Zn-induced
      inhibition in the chloride and nitrate media. (2) Whatever the medium, a higher
      Mn-induced inhibition at pH 5.5 compared to pH 7.4, with much lower Ki values
      under acidic conditions. (3) Elimination of the stimulatory effect of HCO3- by Zn
      but not by Mn. Zn may inhibit a ZIP8-mediated Cd uptake, whereas the Mn-sensitive
      component of uptake would be related to other transport processes.

PMID- 21871557
TI  - Negligible penetration of incidental amounts of alpha-hydroxy acid from rinse-off
      personal care products in human skin using an in vitro static diffusion cell
      model.
AB  - Alpha-hydroxy acids (AHAs), primarily glycolic and lactic acids, are widely used
      in cosmetics to alleviate dyspigmentation, photodamage, and other aging skin
      conditions and as pH adjusters. Glycolic acid reportedly enhances skin damage
      after repeated ultraviolet light exposure, e.g., increased sunburn cell
      formation. This study assessed potential in vitro skin penetration of lactic acid
      and malic acid incorporated into rinse-off personal care products, compared with
      rinse-off and leave-on exposures to glycolic acid (10%, pH 3.5) in a reference
      lotion. Radiolabeled AHA-fortified shampoo, conditioner, and lotion were evenly
      applied as single doses to human epidermal membranes mounted in static diffusion
      cells (not occluded). Exposures were 1-3 min (rinse-off) or 24 h (leave-on).
      Epidermal penetration of malic acid and lactic acid from the rinse-off shampoo
      and conditioner, respectively, was negligible, with >99% removed by rinsing, a
      negligible portion remaining in the stratum corneum (<=0.15%), and even less
      penetrating into the viable epidermis (<=0.04%). Glycolic acid penetration from
      the leave-on reference lotion was 1.42 MUg equiv./cm2/h, with total absorbable
      dose recovery (receptor fluid plus epidermis) of 2.51%, compared to 0.009%,
      0.003%, and 0.04% for the rinse-off reference lotion, shampoo (malic acid), and
      conditioner (lactic acid) exposures, respectively. Dermal penetration of AHAs
      into human skin is pH-, concentration-, and time-dependent. Alpha-hydroxy acids
      in rinse-off shampoos and conditioners are almost entirely removed from the skin
      within minutes by rinsing (resulting in negligible epidermal penetration). This
      suggests that ultraviolet radiation-induced skin effects of AHA-containing rinse
      off products are negligible.

PMID- 21871558
TI  - Feasibility study of the zebrafish assay as an alternative method to screen for
      developmental toxicity and embryotoxicity using a training set of 27 compounds.
AB  - To anticipate to increased testing needs for reproductive toxicity and 3R
      approaches, we studied zebrafish embryo/larva as an alternative for animal
      testing for developmental toxicity and embryotoxicity and evaluated a training
      set of 27 compounds with a standardized protocol. The classification of compounds
      in the zebrafish embryo/larva assay, based on a prediction model using a TI
      (teratogenic index) cut-off value of 2, was compared to available animal and
      human data. When comparing the classification of compounds in the zebrafish
      embryo/larva assay to available animal classification, a sensitivity of 72% and
      specificity of 100% were obtained. The predictive values obtained in comparison
      to a limited set of human data were 50, 60% respectively for teratogens, non
      teratogens. Overall, we demonstrated that the zebrafish embryo/larva assay, may
      be used as screening tool for prioritization of compounds and could contribute to
      reduction of animal experiments in the field of developmental toxicology.

PMID- 21871559
TI  - Activation of promoter activity of the catalytic subunit of gamma
      glutamylcysteine ligase (GCL) in brain endothelial cells by insulin requires
      antioxidant response element 4 and altered glycemic status: implication for GCL
      expression and GSH synthesis.
AB  - Our recent finding that insulin increased the expression of the glutamate
      cysteine ligase catalytic subunit (GCLc) with coincident increases in GCL
      activity and cellular glutathione (GSH) in human brain microvascular endothelial
      cells (IHECs) suggests a role for insulin in vascular GSH maintenance. Here,
      using IHECs stably transfected with promoter-luciferase reporter vectors, we
      found that insulin increased GCLc promoter activity, which required a
      prerequisite increase or decrease in medium glucose. An intact antioxidant
      response element-4 was essential for promoter activation, which was attenuated by
      inhibitors of PI3-kinase/Akt/mTOR signaling. Interestingly, only under low
      glucose conditions did promoter activation correlate with increased GCLc
      expression and GSH synthesis. Low tert-butylhydroperoxide (tBH) concentrations
      similarly mediated promoter activation, but the maximal activation dose was
      decreased 10-fold by insulin. Insulin-tBH coadministration abrogated the low or
      high glucose requirement for promoter activation, suggesting possible ROS
      involvement. ROS production was elevated at low glucose without or with insulin;
      however, GSH increases were not inhibited by tempol, suggesting that ROS did not
      achieve the threshold for driving GCLc promoter activation and de novo GSH
      synthesis. The minor effect of pyruvate also ruled out a major role for
      hypoglycemia (+/-insulin)-induced metabolic stress on GSH induction under these
      conditions.

PMID- 21871560
TI  - Redox regulation of human protease-activated receptor-2 by activated factor X.
AB  - Activated factor X (FXa) exerts coagulation-independent actions such as
      proliferation of vascular smooth muscle cells (SMCs) through the protease
      activated receptors PAR-1 and PAR-2. Both receptors are upregulated upon vascular
      injury but the underlying mechanisms have not been defined. We examined if FXa
      regulates PAR-1 and PAR-2 in human vascular SMCs. FXa increased PAR-2 mRNA,
      protein, and cell-surface expression and augmented PAR-2-mediated mitogenesis.
      PAR-1 was not influenced. The regulatory action of FXa on PAR-2 was concentration
      dependent and mimicked by a PAR-2-selective activating peptide. PAR-2 regulation
      was not influenced by the thrombin inhibitor argatroban or PAR-1 siRNA. FXa
      increased dichlorofluorescein diacetate fluorescence and 8-isoprostane formation
      and induced expression of the NADPH oxidase subunit NOX-1. NOX-1 siRNA prevented
      FXa-stimulated PAR-2 regulation, as did ebselen and cell-permeative and
      impermeative forms of catalase. Exogenous H(2)O(2) increased PAR-2 expression and
      mitogenic activity. FXa promoted nuclear translocation and PAR-2/DNA binding of
      nuclear factor kappaB (NF-kappaB); NF-kappaB inhibition prevented PAR-2
      regulation by FXa. FXa also promoted PAR-2 mRNA stabilization through increased
      human antigen R (HuR)/PAR-2 mRNA binding and cytoplasmic shuttling. HuR siRNA
      abolished FXa-stimulated PAR-2 expression. Thus FXa induces functional expression
      of PAR-2 but not of PAR-1 in human SMCs, independent of thrombin formation, via a
      mechanism involving NOX-1-containing NADPH oxidase, H(2)O(2), NF-kappaB, and HuR.

PMID- 21871561
TI  - AMP-dependent kinase and autophagic flux are involved in aldehyde dehydrogenase-2
      induced protection against cardiac toxicity of ethanol.
AB  - Mitochondrial aldehyde dehydrogenase-2 (ALDH2) alleviates ethanol toxicity
      although the precise mechanism is unclear. This study was designed to evaluate
      the effect of ALDH2 on ethanol-induced myocardial damage with a focus on
      autophagy. Wild-type FVB and transgenic mice overexpressing ALDH2 were challenged
      with ethanol (3g/kg/day, ip) for 3days and cardiac mechanical function was
      assessed using the echocardiographic and IonOptix systems. Western blot analysis
      was used to evaluate essential autophagy markers, Akt and AMPK, and the
      downstream signal mTOR. Ethanol challenge altered cardiac geometry and function
      as evidenced by enlarged ventricular end systolic and diastolic diameters,
      decreased cell shortening and intracellular Ca(2+) rise, prolonged relengthening
      and intracellular Ca(2+) decay, as well as reduced SERCA Ca(2+) uptake, which
      effects were mitigated by ALDH2. Ethanol challenge facilitated myocardial
      autophagy as evidenced by enhanced expression of Beclin, ATG7, and LC3B II, as
      well as mTOR dephosphorylation, which was alleviated by ALDH2. Ethanol challenge
      induced cardiac defect and apoptosis were reversed by the ALDH2 agonist Alda-1,
      the autophagy inhibitor 3-MA, and the AMPK inhibitor compound C, whereas the
      autophagy inducer rapamycin and the AMPK activator AICAR mimicked or exacerbated
      ethanol-induced cell injury. Ethanol promoted or suppressed phosphorylation of
      AMPK and Akt, respectively, in FVB but not ALDH2 murine hearts. Moreover, AICAR
      nullified Alda-1-induced protection against ethanol-triggered autophagic and
      functional changes. Ethanol increased GFP-LC3 puncta in H9c2 cells, the effect of
      which was ablated by Alda-1 and 3-MA. Lysosomal inhibition using bafilomycin A1,
      E64D, and pepstatin A obliterated Alda-1- but not ethanol-induced responses in
      GFP-LC3 puncta. Our results suggest that ALDH2 protects against ethanol toxicity
      through altered Akt and AMPK signaling and regulation of autophagic flux.

PMID- 21871562
TI  - Assessing locomotor activity in larval zebrafish: Influence of extrinsic and
      intrinsic variables.
AB  - The U.S. Environmental Protection Agency is evaluating methods to screen and
      prioritize large numbers of chemicals for developmental toxicity. We are
      exploring methods to detect developmentally neurotoxic chemicals using zebrafish
      behavior at 6 days of age. The behavioral paradigm simultaneously tests
      individual larval zebrafish under both light and dark conditions in a 96-well
      plate using a video tracking system. We have found that many variables affect the
      level or pattern of locomotor activity, including age of the larvae, size of the
      well, and the presence of malformations. Some other variables, however, do not
      appear to affect larval behavior including type of rearing solution (10% Hank's
      vs. 1:3 Danieau vs 60 mg/kg Instant Ocean vs 1* and 1:10* EPA Moderately Hard
      Water). Zebrafish larval behavior using a microtiter plate format may be an ideal
      endpoint for screening developmentally neurotoxic chemicals, but it is imperative
      that many test variables be carefully specified and controlled.

PMID- 21871563
TI  - Selective effects of perinatal ethanol exposure in medial prefrontal cortex and
      nucleus accumbens.
AB  - Ethanol exposure during development is the leading known cause of mental
      retardation and can result in characteristic physiological and cognitive
      deficits, often termed Fetal Alcohol Spectrum Disorders (FASD). Previous
      behavioral findings using rat models of FASD have suggested that there are
      changes in the nucleus accumbens (NAC) and medial prefrontal cortex (mPFC)
      following ethanol exposure during development. This study used a rat model of
      FASD to evaluate dendritic morphology in both the NAC and mPFC and cell number in
      the NAC. Dendritic morphology in mPFC and NAC was assessed using a modified Golgi
      stain and analyzed via three dimensional reconstructions with Neurolucida (MBF
      Bioscience). Cell counts in the NAC (shell and core) were determined using an
      unbiased stereology procedure (Stereo Investigator (MBF Bioscience)). Perinatal
      ethanol exposure did not affect neuronal or glial cell population numbers in the
      NAC. Ethanol exposure produced a sexually dimorphic effect on dendritic branching
      at one point along the NAC dendrites but was without effect on all other measures
      of dendritic morphology in the NAC. In contrast, spine density was reduced and
      distribution was significantly altered in layer II/III neurons of the mPFC
      following ethanol exposure. Ethanol exposure during development was also
      associated with an increase in soma size in the mPFC. These findings suggest that
      previously observed sexually dimorphic changes in activation of the NAC in a rat
      model of FASD may be due to altered input from the mPFC.

PMID- 21871565
TI  - Cerebellar defects in Pdss2 conditional knockout mice during embryonic
      development and in adulthood.
AB  - PDSS2 is a gene that encodes one of the two subunits of trans-prenyl diphosphate
      synthase that is essential for ubiquinone biosynthesis. It is known that
      mutations in PDSS2 can cause primary ubiquinone deficiency in humans and a
      similar disease in mice. Cerebellum is the most often affected organ in
      ubiquinone deficiency, and cerebellar atrophy has been diagnosed in many infants
      with this disease. In this study, two Pdss2 conditional knockout mouse lines
      directed by Pax2-cre and Pcp2-cre were generated to investigate the effect of
      ubiquinone deficiency on cerebellum during embryonic development and in
      adulthood, respectively. The Pdss2(f/-); Pax2-cre mouse recapitulates some
      symptoms of ubiquinone deficiency in infants, including severe cerebellum
      hypoplasia and lipid accumulation in skeletal muscles at birth. During early
      cerebellum development (E12.5-14.5), Pdss2 knockout initially causes the delay of
      radial glial cell growth and neuron progenitor migration, so the growth of mutant
      cerebellum is retarded. During later development (E15.5-P0), increased ectopic
      apoptosis of neuroblasts and impaired cell proliferation result in the
      progression of cerebellum hypoplasia in the mutant. Thus, the mutant cerebellum
      contains fewer neurons at birth, and the cells are disorganized. The
      developmental defect of mutant cerebellum does not result from reduced Fgf8
      expression before E12.5. Electron microscopy reveals mitochondrial defects and
      increased autophagic-like vacuolization that may arise in response to abnormal
      mitochondria in the mutant cerebellum. Nevertheless, the mutant mice die soon
      after birth probably due to cleft palate and micrognathia, which may result from
      Pdss2 knockout caused by ectopic Pax2-cre expression in the first branchial arch.
      On the other hand, the Pdss2(f/-); Pcp2-cre mouse is healthy at birth but
      gradually loses cerebellar Purkinje cells and develops ataxia-like symptoms at
      9.5 months; thus this conditional knockout mouse may serve as a model for
      ubiquinone deficiency in adult patients. In conclusion, this study provides two
      mouse models of Pdss2 based ubiquinone deficiency. During cerebellum development,
      Pdss2 knockout results in severe cerebellum hypoplasia by impairing cell
      migration and eliciting ectopic apoptosis, whereas Pdss2 knockout in Purkinje
      cells at postnatal stages leads to the development of cerebellar ataxia.

PMID- 21871564
TI  - Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human
      bronchial epithelial cells.
AB  - Lysophosphatidic acid (LPA), a naturally occurring bioactive lysophospholipid
      increases the expression of both pro-inflammatory and anti-inflammatory mediators
      in airway epithelial cells. Soluble ST2 (sST2), an anti-inflammatory mediator,
      has been known to function as a decoy receptor of interleukin (IL)-33 and
      attenuates endotoxin-induced inflammatory responses. Here, we show that LPA
      increased sST2 mRNA expression and protein release in a dose and time dependent
      manner in human bronchial epithelial cells (HBEpCs). LPA receptors antagonist and
      Galphai inhibitor, pertussis toxin, attenuated LPA-induced sST2 release.
      Inhibition of NF-kappaB or JNK pathway reduced LPA-induced sST2 release. LPA
      treatment decreased histone deacetylase 3 (HDAC3) expression and enhanced
      acetylation of histone H3 at lysine 9 that binds to the sST2 promoter region.
      Furthermore, limitation of intracellular LPA generation by the down-regulation of
      acetyl glycerol kinase attenuated exogenous LPA-induced histone H3 acetylation on
      sST2 promoter region, as well as sST2 gene expression. Treatment of HBEpCs with
      recombinant sST2 protein or sST2-rich cell culture media attenuated endotoxin
      induced phosphorylation of PKC and airway epithelial barrier disruption. These
      results unravel a novel sST2 mediated signaling pathway that has physiological
      relevance to airway inflammation and remodeling.

PMID- 21871566
TI  - CX3CR1 deficiency exacerbates neuronal loss and impairs early regenerative
      responses in the target-ablated olfactory epithelium.
AB  - The olfactory epithelium is a site of sustained adult neurogenesis where
      olfactory sensory neurons are continuously replaced from endogenous
      stem/progenitor cells. Epithelial macrophages have been implicated in the
      phagocytosis of degenerating cells but the molecular mechanisms allowing for
      their recruitment and activation while maintaining a neurogenic microenvironment
      are poorly understood. We have previously shown that the chemokine fractalkine
      (CX3CL1) is expressed by olfactory sensory neurons and ensheathing cells in the
      olfactory epithelium. In turn, the fractalkine receptor, CX3CR1, is expressed on
      macrophages and dendritic cells within the olfactory epithelium. We report that a
      selective cell death of olfactory sensory neurons in the epithelium of CX3CR1
      deficient mice via target ablation (i.e. olfactory bulbectomy) results in an
      exacerbated loss of olfactory sensory neurons compared to wild-type mice. In
      addition, reduced proliferation of intraepithelial stem/progenitor cells was
      observed in lesioned CX3CR1-deficient mice, suggesting an impaired regenerative
      response. Importantly, a lack of CX3CL1-signaling caused increased recruitment of
      macrophages into the olfactory epithelium, which in turn contained higher levels
      of pro-inflammatory cytokines (e.g. TNF-alpha and IL-6) as determined by qPCR. We
      also present novel data showing that, relative to wild-type, CX3CR1-deficient
      macrophages have diminished phagocytic activity following stimulation with
      CX3CL1. Collectively, our data indicate that signaling through the CX3CR1
      receptor modulates macrophage activity, resulting in an environment conducive to
      olfactory sensory neuron clearance and targeted replacement from endogenous
      stem/progenitor cells.

PMID- 21871567
TI  - Two catalase homologs are involved in host protection against bacterial infection
      and oxidative stress in Crassostrea hongkongensis.
AB  - Catalase is one of the key antioxidant enzymes and it appears to be involved in
      protection against immune infection and oxidative stress. Here, two catalase
      cDNAs (ChCat-1 and ChCat-2) were isolated from hemocytes of Crassostrea
      hongkongensis using SSH and RACE. The full-length cDNAs of ChCat-1 and ChCat-2
      are 1913 and 2466 bp in length, encoding proteins of 515 and 511 amino acids,
      respectively. Multiple alignments of amino acid sequences revealed that both
      ChCat-1 and ChCat-2 possess several characteristic features of the catalase
      family of enzymes, including one proximal active site signature, one heme-ligand
      signature, and three catalytic amino acid residues (His(72), Asn(145) and
      Tyr(355)). Phylogenetic analysis indicates that these two catalases may share a
      common ancestral gene and result from a gene duplication event following the
      divergence of bivalves and gastropods. Constitutive expression of ChCat-1 and
      ChCat-2 was observed in all tissues studied, with highest levels of expression in
      gill and muscle, respectively. The expression of both genes was inducible by
      bacterial infection, and reached the maximum at 8 h (9.0-fold) and 12 h (2.3
      fold) post-infection, respectively. Furthermore, both the purified ChCat-1 and
      ChCat-2 protein displayed a strong catalase activity, and S2 cells carrying ChCat
      1 or ChCat-2 showed a higher degree of resistance to H(2)O(2) than that of
      control cells. In a word, this is the first report of the presence of two
      catalase genes in a single marine bivalve, and our results highlight the
      involvement of both ChCat-1 and ChCat-2 in host protection against pathogen
      infection and oxidative stress in C. hongkongensis.

PMID- 21871568
TI  - Prokaryotic expression, purification, and refolding of leukocyte cell-derived
      chemotaxin 2 and its effect on gene expression of head kidney-derived macrophages
      of a teleost fish, ayu (Plecoglossus altivelis).
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2) is reported to be an immunorelevant
      protein in ayu (Plecoglossus altivelis). In this study, ayu LECT2 mature peptide
      (aLECT2m) was expressed as insoluble inclusion bodies in Escherichia coli. The
      denatured recombinant aLECT2m (raLECT2m) was refolded by a size-exclusion
      chromatography refolding process achieved by using arginine-containing mobile
      phase and a decreasing urea gradient. The in vitro chemotactic activity assay
      showed that the refolded raLECT2m had the bioactivity. By using suppression
      subtractive hybridization (SSH) method, we further identified up-regulated genes
      in ayu macrophages treated with refolded raLECT2m. These genes were tightly
      involved in endocytosis, hydrolysis, transcriptional regulation, signal
      transduction, and so on. Moreover, real-time quantitative PCR (RT-qPCR) results
      confirmed that selected 10 genes expression was significantly up-regulated in
      refolded raLECT2m-treated ayu macrophages. This study provides a basis for
      further studies of the mechanism of cytokine LECT2 in fish immune responses.

PMID- 21871569
TI  - Brain functional connectivity in stimulant drug dependence and obsessive
      compulsive disorder.
AB  - There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug
      dependence, although conventionally distinct diagnostic categories, might share
      important cognitive and neurobiological substrates. We tested this hypothesis
      directly by comparing brain functional connectivity measures between patients
      with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent
      users of other recreational drugs) and healthy volunteers. We measured functional
      connectivity between each possible pair of 506 brain regional functional MRI time
      series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics
      in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used
      permutation tests to identify i) brain regions where strength of connectivity was
      significantly different in both patient groups compared to healthy volunteers;
      and ii) brain regions and connections which had significantly different
      functional connectivity between patient groups. We found that functional
      connectivity of right inferior and superior orbitofrontal cortex (OFC) was
      abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients
      with higher scores on measures of compulsive symptom severity showed greater
      reductions of right orbitofrontal connectivity. Functional connections
      specifically between OFC and dorsal medial pre-motor and cingulate cortex were
      attenuated in both patient groups. However, patients with OCD demonstrated more
      severe and extensive reductions of functional connectivity compared to SDIs. OCD
      and stimulant dependence are not identical at the level of brain functional
      systems but they have some important abnormalities in common compared with
      healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems
      biomarker for compulsivity across diagnostic categories.

PMID- 21871570
TI  - Magnetic resonance imaging of the Amine-Proton EXchange (APEX) dependent
      contrast.
AB  - Chemical exchange between water and labile protons from amino-acids, proteins and
      other molecules can be exploited to provide tissue contrast with magnetic
      resonance imaging (MRI) techniques. Using an off-resonance Spin-Locking (SL)
      scheme for signal preparation is advantageous because the image contrast can be
      tuned to specific exchange rates by adjusting SL pulse parameters. While the
      amide-proton transfer (APT) contrast is obtained optimally with steady-state
      preparation, using a low power and long irradiation pulse, image contrast from
      the faster amine-water proton exchange (APEX) is optimized in the transient state
      with a higher power and a shorter SL pulse. Our phantom experiments show that the
      APEX contrast is sensitive to protein and amino acid concentration, as well as
      pH. In vivo 9.4-T SL MRI data of rat brains with irradiation parameters optimized
      to slow exchange rates have a sharp peak at 3.5 ppm and also broad peak at -2 to 
      5 ppm, inducing negative contrast in APT-weighted images, while the APEX image
      has large positive signal resulting from a weighted summation of many different
      amine-groups. Brain ischemia induced by cardiac arrest decreases pure APT signal
      from ~1.7% to ~0%, and increases the APEX signal from ~8% to ~16%. In the middle
      cerebral artery occlusion (MCAO) model, the APEX signal shows different spatial
      and temporal patterns with large inter-animal variations compared to APT and
      water diffusion maps. Because of the similarity between the chemical exchange
      saturation transfer (CEST) and SL techniques, APEX contrast can also be obtained
      by a CEST approach using similar irradiation parameters. APEX may provide useful
      information for many diseases involving a change in levels of proteins, peptides,
      amino-acids, or pH, and may serve as a sensitive neuroimaging biomarker.

PMID- 21871571
TI  - Learning to play a melody: an fMRI study examining the formation of auditory
      motor associations.
AB  - Interactions between the auditory and motor systems are important for music and
      speech, and may be especially relevant when one learns to associate sounds with
      movements such as when learning to play a musical instrument. However, little is
      known about the neural substrates underlying auditory-motor learning. This study
      used fMRI to investigate the formation of auditory-motor associations while
      participants with no musical training learned to play a melody. Listening to
      melodies before and after training activated the superior temporal gyrus
      bilaterally, but neural activity in this region was significantly reduced on the
      right when participants listened to the trained melody. When playing melodies and
      random sequences, activity in the left dorsal premotor cortex (PMd) was reduced
      in the late compared to early phase of training; learning to play the melody was
      also associated with reduced neural activity in the left ventral premotor cortex
      (PMv). Participants with the highest performance scores for learning the melody
      showed more reduced neural activity in the left PMd and PMv. Learning to play a
      melody or random sequence involves acquiring conditional associations between key
      presses and their corresponding musical pitches, and is related to activity in
      the PMd. Learning to play a melody additionally involves acquisition of a learned
      auditory-motor sequence and is related to activity in the PMv. Together, these
      findings demonstrate that auditory-motor learning is related to the reduction of
      neural activity in brain regions of the dorsal auditory action stream, which
      suggests increased efficiency in neural processing of a learned stimulus.

PMID- 21871572
TI  - Electrophysiological signatures of intentional social coordination in the 10-12
      Hz range.
AB  - This study sought to investigate the effects of manipulating social coordination
      on brain synchronization/de-synchronization in the mu band. Mu activation is
      associated with understanding and coordinating motor acts and may play a key role
      in mediating social interaction. Members of a dyad were required to interact with
      one another in a rhythmic finger movement coordination task under various
      instructions: intrinsic where each member of the dyad was instructed to maintain
      their own and ignore their partner's movement; in-phase where they were asked to
      synchronize with their partner's movement; and anti-phase where they were
      instructed to syncopate with their partner's movement. EEG and movement data were
      recorded simultaneously from both subjects during all three tasks and a control
      condition. Log power ratios of EEG activity in the active conditions versus
      control were used to assess the effect of task context on synchronization/de
      synchronization in the mu spectral domain. Results showed clear and systematic
      modulation of mu band activity in the 10-12 Hz range as a function of
      coordination context. In the left hemisphere general levels of alpha-mu
      suppression increased progressively as one moved from intrinsic through in-phase
      to anti-phase contexts but with no specific central-parietal focus. In contrast
      the right hemisphere displayed context-specific changes in the central-parietal
      region. The intrinsic condition showed a right synchronization which disappeared
      with the in-phase context even as de-synchronization remained greater in the left
      hemisphere. Anti-phase was associated with larger mu suppression in the right in
      comparison with left at central-parietal region. Such asymmetrical changes were
      highly correlated with changing behavioral dynamics. These specific patterns of
      activation and deactivation of mu activity suggest that localized neural
      circuitry in right central-parietal regions mediates how individuals interpret
      the movements of others in the context of their own actions. A right sided
      mechanism in the 10-12 Hz range appears to be involved in integrating the mutual
      information among the members of a dyad that enables the dynamics of social
      interaction to unfold in time.

PMID- 21871573
TI  - PHYCAA: data-driven measurement and removal of physiological noise in BOLD fMRI.
AB  - The effects of physiological noise may significantly limit the reproducibility
      and accuracy of BOLD fMRI. However, physiological noise evidences a complex,
      undersampled temporal structure and is often non-orthogonal relative to the
      neuronally-linked BOLD response, which presents a significant challenge for
      identifying and removing such artifact. This paper presents a multivariate, data
      driven method for the characterization and removal of physiological noise in fMRI
      data, termed PHYCAA (PHYsiological correction using Canonical Autocorrelation
      Analysis). The method identifies high frequency, autocorrelated physiological
      noise sources with reproducible spatial structure, using an adaptation of
      Canonical Correlation Analysis performed in a split-half resampling framework.
      The technique is able to identify physiological effects with vascular-linked
      spatial structure, and an intrinsic dimensionality that is task- and subject
      dependent. We also demonstrate that increasing dimensionality of such
      physiological noise is correlated with increasing variability in externally
      measured respiratory and cardiac processes. Using PHYCAA as a denoising technique
      significantly improves simulated signal detection with physiological noise, and
      real data-driven model prediction and reproducibility, for both block and event
      related task designs. This is demonstrated compared to no physiological noise
      correction, and to the widely used RETROICOR (Glover et al., 2000) physiological
      denoising algorithm, which uses externally measured cardiac and respiration
      signals.

PMID- 21871574
TI  - The genetic legacy of aridification: climate cycling fostered lizard
      diversification in Australian montane refugia and left low-lying deserts
      genetically depauperate.
AB  - It is a widely held assumption that populations historically restricted to
      mountain refugia tend to exhibit high levels of genetic diversity and deep
      coalescent histories, whereas populations distributed in surrounding low-lying
      regions tend to be genetically depauperate following recent expansion from
      refugia. These predicted genetic patterns are based largely on our understanding
      of glaciation history in Northern Hemisphere systems, yet remain poorly tested in
      analogous Southern Hemisphere arid systems because few examples in the literature
      allow the comparison of widespread taxa distributed across mountain and desert
      biomes. We demonstrate with multiple datasets from Australian geckos that
      topographically complex mountain regions harbor high nucleotide diversity, up to
      18 times higher than that of the surrounding desert lowlands. We further
      demonstrate that taxa in topographically complex areas have older coalescent
      histories than those in the geologically younger deserts, and that both ancient
      and more recent aridification events have contributed to these patterns. Our
      results show that, despite differences in the details of climate and landscape
      changes that occurred in the Northern and Southern hemispheres (ice-sheets versus
      aridification), similar patterns emerge that illustrate the profound influence of
      the Pleistocene on contemporary genetic structure.

PMID- 21871575
TI  - Selective decontamination by antimicrobials during long term treatment:
      perspectives for saving host indigenous microbiota.
AB  - Short bowel syndrome (SBS) occurs in patients fed total parenteral nutrition
      (TPN) after massive intestinal resection. TPN weaning is often associated with
      occlusion or sepsis. In the present study the intestinal biotope was investigated
      in young patients (n = 14) with massive intestinal resection and recurrent
      symptoms of sepsis or occlusion during enteral food introduction. They were
      treated by aminosides for a long term period. Ileal effluents were collected for
      enumerating bacteria. In some case, blood and rectal specimen were also
      collected. A few patients developed bacterial overgrowth (1), occlusion (1),
      sepsis (4), osteoarthritis (1) or pneumonia (1) during the survey. A drastic drop
      of bifidobacteria that was not prevented by human milk feeding was observed prior
      occlusion or respiratory infection. Detection of clostridial vegetative forms
      preceded sepsis and decrease in clostridia parallelled recovery. In conclusion,
      onset of symptoms was related with extreme imbalance of the ileal flora.
      Supplementation with bifidobacterial compounds that were well tolerated in two
      patients could be of interest in children with recurrent symptoms.

PMID- 21871576
TI  - Molecular cloning and expression of long-wavelength-sensitive cone opsin in the
      brain of a tropical damselfish.
AB  - Ovarian development of the sapphire devil, Chrysiptera cyanea, exhibits
      photoperiodism and is stimulated under long-day conditions. Previous studies
      suggest that red light is more effective than green and blue lights for inducing
      ovarian development. In addition, the extra-retinal photoreception involved in
      the ovarian development is suggested in this species. The present study aimed to
      clone the red-light-sensitive cone opsin (sdLWS) of this species, to demonstrate
      its expression in the brain, and to confirm the effectiveness of red light on the
      initiation of ovarian development. A phylogenetic analysis revealed that sdLWS
      belongs to the long-wavelength-sensitive opsin (LWS opsin) group, showing high
      identity (77-92%) with the LWS opsin of other fishes. RT-PCR showed that sdLWS is
      expressed in the eye, brain, and ovary. In situ hybridization indicated that
      sdLWS is expressed in the third ventricle periventricular area in the anterior
      hypothalamus. Exposing fish to long-day conditions of red light resulted in the
      appearance of vitellogenic oocytes in the ovary and an increase in the
      gonadosomatic index within 2weeks, suggesting that fish immediately undergo
      oocyte development under red light conditions. These results indicate that sdLWS
      is a possible candidate of deep brain photoreceptor molecule involved in
      photoperiodic ovarian development in the sapphire devil.

PMID- 21871577
TI  - Digesta retention time in the Galapagos tortoise (Chelonoidis nigra).
AB  - The retention time of food in the digestive tract of animals has important
      implications for digestive physiology. Retention time impacts digestive
      efficiency and among herbivores affects plant-animal interactions including
      herbivory and seed dispersal. Poorly studied yet iconic Galapagos tortoises are
      large-bodied generalist herbivores and ecosystem engineers which migrate
      seasonally. Potentially variable digesta retention times due to strong seasonal
      and altitudinal temperature gradients may influence tortoise seed dispersal
      abilities and rates of herbivory. We fed captive adult tortoises living in semi
      natural conditions on Galapagos with inert particles and seeds from locally
      available fruits to determine whether seed size and ambient temperature
      influenced retention time. Median retention time varied from 6 to 28days, with a
      mode of 12days. Seed size had no effect on any of our measures of retention time,
      but ambient temperature was inversely correlated with retention times. Long
      retention time facilitates long distance seed dispersal by Galapagos tortoises,
      which may improve effectiveness. The effect of temperature, which may double from
      hot lowlands to cold highlands through the seasonal cycle, on tortoise digesta
      retention time will strongly influence seed dispersal efficiency and may
      influence patterns of food selection and migration in this species.

PMID- 21871578
TI  - Mitochondrial respiratory control and early defects of oxidative phosphorylation
      in the failing human heart.
AB  - Heart failure is a consequence of progressive deterioration of cardiac
      performance. Little is known about the role of impaired oxidative phosphorylation
      in the progression of the disease, since previous studies of mitochondrial
      injuries are restricted to end-stage chronic heart failure. The present study
      aimed at evaluating the involvement of mitochondrial dysfunction in the
      development of human heart failure. We measured the control of oxidative
      phosphorylation with high-resolution respirometry in permeabilized myocardial
      fibres from donor hearts (controls), and patients with no or mild heart failure
      but presenting with heart disease, or chronic heart failure due to dilated or
      ischemic cardiomyopathy. The capacity of the phosphorylation system exerted a
      strong limitation on oxidative phosphorylation in the human heart, estimated at
      121 pmol O(2)s(-1)mg(-1) in the healthy left ventricle. In heart disease, a
      specific defect of the phosphorylation system, Complex I-linked respiration, and
      mass-specific fatty acid oxidation were identified. These early defects were also
      significant in chronic heart failure, where the capacities of the oxidative
      phosphorylation and electron transfer systems per cardiac tissue mass were
      decreased with all tested substrate combinations, suggesting a decline of
      mitochondrial density. Oxidative phosphorylation and electron transfer system
      capacities were higher in ventricles compared to atria, but the impaired
      mitochondrial quality was identical in the four cardiac chambers of chronic heart
      failure patients. Coupling was preserved in heart disease and chronic heart
      failure, in contrast to the mitochondrial dysfunction observed after prolonged
      cold storage of cardiac tissue. Mitochondrial defects in the phosphorylation
      system, Complex I respiration and mass-specific fatty acid oxidation occurred
      early in the development of heart failure. Targeting these mitochondrial injuries
      with metabolic therapy may offer a promising approach to delay the progression of
      heart disease.

PMID- 21871579
TI  - Investigation of genotoxic and cytotoxic effects of micro- and nanosized titanium
      dioxide in six organs of mice in vivo.
AB  - Titanium dioxide is manufactured worldwide in large quantities for use in a wide
      range of applications including as food additives, in cosmetics and pigments for
      coloring ingested and externally applied drugs. Although TiO(2) is chemically
      inert it can cause negative health effects, such as lung cancer in rats. However,
      the mechanisms involved in TiO(2)-induced genotoxicity and carcinogenicity have
      not been clearly defined and are poorly studied in vivo. In the present research
      genotoxicity and carcinogenicity of titanium dioxide were studied in a mouse
      model. We treated CBAB6F1 mice by oral gavage with titanium dioxide particles
      (microsized, TDM, 160nm; nanosized, TDN, 33nm) in doses of 40, 200 and 1000mg/kg
      bw, daily for seven days. Genotoxic effects were analyzed in the cells of brain,
      liver and bone marrow by means of the Comet assay and in the cells of bone
      marrow, forestomach, colon and testis with a poly-organ karyological assay
      (analysis of micronuclei, nuclear protrusions, atypical nuclei, multinucleated
      cells, mitotic and/or apoptotic index). TDM induced DNA-damage and micronuclei in
      bone-marrow cells and TDN induced DNA-damage in the cells of bone marrow and
      liver. TDM and TDN increased the mitotic index in forestomach and colon
      epithelia, the frequency of spermatids with two and more nuclei, and apoptosis in
      forestomach (only TDN) and testis. This is one of the first poly-organ studies of
      TDM- and TDN-induced genotoxicity in vivo in mice. These effects are caused by a
      secondary genotoxic mechanism associated with inflammation and/or oxidative
      stress. Given the increasing use of TiO(2) nanoparticles, these findings indicate
      a potential health hazard associated with exposure to TiO(2) particles.

PMID- 21871580
TI  - Analysis of aflatoxin-B1-degrading microbes by use of a combined toxicity
      profiling method.
AB  - To monitor cytotoxic and genotoxic effects of aflatoxin, a luminescent assay
      employing Aliivibrio fischeri as a test organism and a colorimetric assay based
      on the SOS-Chromotest were adapted to our needs. The aim of this method
      developing work was to be able to select - from a collection of environmental
      isolates - microbes that degrade aflatoxin without production of harmful
      intermediates and by-products, in a fast and cost-effective way. By the
      combination of the two modified assays, microbes that met these criteria have
      been successfully selected. Among thirty-three isolates, the strain Rhodococcus
      rhodochrous NI2 proved to be the best aflatoxin-B1-degrading microbe, with the
      weakest harmful biological effects throughout aflatoxin-B1-degradation. Our
      findings underline the necessity to employ bio-tests in biodegradation assays, as
      cytotoxicity and/or genotoxicity may occur even after substantial degradation of
      the toxins.

PMID- 21871581
TI  - Rapid detection of Opisthorchis viverrini copro-DNA using loop-mediated
      isothermal amplification (LAMP).
AB  - Opisthorchis viverrini and other foodborne trematode infections are major health
      problem in Thailand, the Lao People's Democratic Republic, Vietnam and Cambodia.
      Differential diagnosis of O. viverrini based on the microscopic observation of
      parasite eggs is difficult in areas where Clonorchis sinensis and minute
      intestinal flukes coexist. We therefore established a rapid, sensitive and
      specific method for detecting O. viverrini infection from the stool samples using
      the loop-mediated isothermal amplification (LAMP) method. A total of five primers
      from seven regions were designed to target the internal transcribed spacer 1
      (ITS1) in ribosomal DNA for specific amplification. Hydroxy naphthol blue (HNB)
      was more effective to detect the LAMP product compared to the Real-time LAMP and
      turbidity assay for its simple and distinct detection. The LAMP assay
      specifically amplified O. viverrini ITS1 but not C. sinensis and minute
      intestinal flukes with the limit of detection around 10(-3)ng DNA/MUL. The
      sensitivity of the LAMP was 100% compared to egg positive samples. While all
      microscopically positive samples were positive by LAMP, additionally 5 of 13
      (38.5%) microscopically negative samples were also LAMP positive. The technique
      has great potential for differential diagnosis in endemic areas with mixed O.
      viverrini and intestinal fluke infections. As it is an easy and simple method,
      the LAMP is potentially applicable for point-of-care diagnosis.

PMID- 21871582
TI  - Contribution of efflux activity to isoniazid resistance in the Mycobacterium
      tuberculosis complex.
AB  - Resistance to isoniazid (INH), one of the main drugs used in tuberculosis (TB)
      therapy, is mostly due to chromosomal mutations in target genes. However,
      approximately 20-30% of INH resistant Mycobacterium tuberculosis isolates do not
      have mutations in any of the genes associated with INH resistance. This suggests
      that other mechanism(s) may be involved, namely efflux pump systems capable of
      extruding the drug to the exterior of the cell. In a previous work, we have
      induced clinical INH susceptible M. tuberculosis isolates and the H37Rv reference
      strain to high-level resistance to INH, by gradual exposure to increasing
      concentrations of this drug. In the present study, we have characterized these
      strains and Mycobacterium bovis BCG induced to INH resistance with respect to
      their efflux activity and its contribution to INH resistance using the following
      approach: determination of the susceptibility to INH in the presence and absence
      of the efflux inhibitors (EIs) chlorpromazine, thioridazine and verapamil;
      evaluation of efflux activity by a semi-automated fluorometric method; and
      quantification of the expression level of genes coding for efflux pumps by real
      time RT-qPCR. The EIs decreased INH resistance in the INH induced strains, in
      particular verapamil promoted a reversal of resistance in some of the strains
      tested. The induced strains presented an increased efflux activity that was
      inhibited by the EIs and showed overexpression of the efflux pump genes efpA,
      mmpL7, mmr, p55 and the Tap-like gene Rv1258c. Altogether, these results
      correlate efflux activity with INH resistance and demonstrate that efflux pumps
      play an important role in acquired INH resistance in M. tuberculosis complex. The
      development of EIs that can restore the antimicrobial activity of the antibiotic
      subject to efflux is an approach that can be useful in order to prevent the
      emergence of this resistance and guide the development of new effective anti-TB
      therapeutical approaches.

PMID- 21871583
TI  - Expansion of European vacA and cagA alleles to East-Asian Helicobacter pylori
      strains in Cambodia.
AB  - Helicobacter pylori infection is associated with gastric cancer (GC). The highest
      incidence rates have been described in Asia, but regional variations exist that
      do not match the distribution of infection prevalence rates. The aim of the study
      was to examine the possible contribution of H. pylori virulence factors to
      geographic differences in the incidence of GC across East and Southeast Asia. We
      studied 66 isolates from Cambodian patients that had previously been assigned to
      two genetic populations based on sequences of seven housekeeping genes, namely
      hpEurope (n = 34, 51.5%) and hpEastAsia, subpopulation hspEAsia (n = 32, 48.5%).
      These strains were characterized with respect to vacA polymorphism and cagA
      status by PCR, and the CagA C-terminal region was sequenced. We also sequenced
      the complete cagA gene from 10 hpEurope and 10 hspEAsia strains chosen at random.
      The cagA gene was present in 92.4% of the 66 isolates and was mainly of Western
      type (n = 36, 59.0%). hspEAsia strains carrying East-Asian CagA and the m1-type
      vacA allele (15.2%) were less frequent among the 66 Cambodian isolates than
      reported in East Asian countries, a finding that might partly explain the
      intermediate incidence of GC in Cambodia, and by extension, in Southeast Asia
      (except for Vietnam). The observed high prevalence of s1a alleles (34.4%) and
      Western CagA (28.1%) among hspEAsia strains indicates frequent introgression of
      European vacA and cagA alleles into East Asian H. pylori strains. This expansion
      might have severe consequences for individual disease outcome.

PMID- 21871584
TI  - Multilocus genotyping reveals a polyphyletic pattern among naturally antimony
      resistant Leishmania braziliensis isolates from Peru.
AB  - In order to understand the epidemiological dynamics of antimonial (Sb(V))
      resistance in zoonotic tegumentary leishmaniasis and its link with treatment
      outcome, we analyzed the population structure of 24 Peruvian Leishmania
      braziliensis clinical isolates with known in vitro antimony susceptibility and
      clinical phenotype by multilocus microsatellite typing (14 microsatellite loci).
      The genetic variability in the Peruvian isolates was high and the multilocus
      genotypes were strongly differentiated from each other. No correlation was found
      between the genotypes and in vitro drug susceptibility or clinical treatment
      outcome. The finding of a polyphyletic pattern among the Sb(V)-resistant L.
      braziliensis might be explained by (i) independent events of drug resistance
      emergence, (ii) sexual recombination and/or (iii) other phenomena mimicking
      recombination signals. Interestingly, the polyphyletic pattern observed here is
      very similar to the one we observed in the anthroponotic Leishmania donovani
      (Laurent et al., 2007), hereby questioning the role of transmission and/or
      chemotherapeutic drug pressure in the observed population structure.

PMID- 21871586
TI  - Pyridoxal phosphate enzymology.

PMID- 21871585
TI  - Efficacy of oral administration of heat-killed probiotics from Mongolian dairy
      products against influenza infection in mice: alleviation of influenza infection
      by its immunomodulatory activity through intestinal immunity.
AB  - Some probiotics possess immunomodulatory activities and have been used as
      complementary and alternative medicines. We previously found that 10 lactic acid
      bacteria (LAB) strains isolated from traditional Mongolian dairy products showed
      probiotic potential in vitro. In this study, we assessed the immunomodulatory
      activity of 10 LABs on influenza virus (IFV) infection in relation to their
      efficacies in IFV-infected mice. In an intranasal IFV infection model in mice,
      oral administration of boiled Lactobacillus plantarum 06CC2 strain (20mg/mouse),
      one of the 10 LABs, twice daily for 10 days starting two days before infection
      was significantly effective in protecting the body weight loss of infected mice,
      reducing virus yields in the lungs on days 2, 4, and 6 after infection, and
      prolonging survival times without toxicity. The total numbers of infiltrated
      cells in the bronchoalveolar lavage fluid (BALF), especially macrophages and
      neutrophils, were significantly reduced by 06CC2 administration on day 2. On day
      2, tumor necrosis factor (TNF)-alpha production in BALF was also reduced
      significantly, but interferon-alpha, interleukin-12, and interferon-gamma
      productions were augmented and natural killer (NK) cell activity was
      significantly elevated. Furthermore, the gene expressions of interleukin-12
      receptor and interferon-gamma in Peyer's patches were augmented by 06CC2
      administration on day 2. Thus, 06CC2 was suggested to alleviate influenza
      symptoms in mice in correlation with the augmentation of NK cell activity
      associated with the enhancement of interferon-alpha and Th1 cytokine productions
      through intestinal immunity and the reduction of TNF-alpha in the early stage of
      infection.

PMID- 21871587
TI  - Precipitation by lanthanum ions: a straightforward approach to isolating
      phosphoproteins.
AB  - Posttranslational modification (PTM) of proteins, particularly phosphorylation,
      is a key element in the regulation of cell functions. In many signal transduction
      processes, PTM is a pivotal step. Various analytical methods have been proposed
      for the identification of phosphoproteins; however, most of these methods require
      sophisticated equipment. Here we present an easily applicable method of
      phosphoprotein enrichment. This method is based on single-step precipitation by
      lanthanum chloride and allows subsequent protein identification by matrix
      assisted laser desorption/ionization-mass spectrometry (MALDI-TOF-MS). The method
      proved its suitability for the isolation of phosphoproteins from frozen tissue
      and cultured cells samples after cell lysis in various buffer systems
      (urea/thiourea and EGTA/EDTA). The tests revealed that the isolation of
      phosphoproteins can be achieved with high efficiency even from complex protein
      mixtures. Our results indicate that lanthanum-based enrichment of phosphoproteins
      can be a useful tool in phosphoproteomic studies.

PMID- 21871589
TI  - A randomized, double-blind, placebo-controlled, single-dose study to evaluate the
      safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab
      administered subcutaneously to postmenopausal Japanese women.
AB  - Denosumab is a fully human monoclonal antibody that has high affinity for RANK
      ligand (RANKL). RANKL is the essential mediator of osteoclast formation, function
      and survival. The safety, tolerability, pharmacokinetics (PK) and
      pharmacodynamics (PD) of denosumab in healthy postmenopausal Japanese women were
      assessed. This was a randomized, double-blind, dose-escalation study in which 40
      subjects received denosumab at doses of 0.03, 0.1, 0.3, 1.0 or 3.0mg/kg, or
      placebo administered subcutaneously. Blood and urine samples for determination of
      serum denosumab, CTX-I, NTX-I/Cr, bone specific alkaline phosphatase (bone ALP)
      and intact parathyroid hormone (iPTH) were collected. The PK and PD time profiles
      were compared to those obtained in separate studies conducted in the US. No
      serious adverse events occurred and all subjects completed this study. Denosumab
      demonstrated nonlinear PK and dose- and concentration-dependent dispositions. The
      maximum mean decrease from baseline ranged from 65% to 95% for CTX-I
      concentrations and from 50% to 85% for NTX-I/Cr. Additionally, the changes were
      dose-dependent. The suppression of bone turnover markers was rapid (within 2 days
      after dosing) and duration of suppression was dose-dependent. No marked
      differences in the PK and PD profiles between Japanese and non-Japanese subjects
      were noted. The observed results indicate that denosumab may have therapeutic
      potential for conditions resulting from increased bone turnover, such as
      osteoporosis in Japanese.

PMID- 21871590
TI  - N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular
      (LV) systolic dysfunction independent of fixed coronary disease or coronary
      spastic pathogenesis. A number of investigators have documented marked elevation
      of natriuretic peptide levels at presentation in such patients. We sought to
      determine the pattern, extent, and determinants of the release of N-terminal pro
      B type natriuretic peptide/B type natriuretic peptide (NT-proBNP/BNP) in patients
      with TTC. We evaluated NT-proBNP/BNP release acutely and during the first 3
      months in 56 patients with TTC (96% women, mean age 69 +/- 11 years). The peak
      plasma NT-proBNP levels were compared to the pulmonary capillary wedge pressure
      and measures of regional and global LV systolic dysfunction (systolic wall
      stress, wall motion score index, and LV ejection fraction) as potential
      determinants of NT-proBNP/BNP release. In patients with TTC, the plasma
      concentrations of NT-proBNP (median 4,382 pg/ml, interquartile range 2,440 to
      9,019) and BNP (median 617 pg/ml, interquartile range 426 to 1,026) were
      substantially elevated and increased significantly during the first 24 hours
      after the onset of symptoms (p = 0.001), with slow and incomplete resolution
      during the 3 months thereafter. The peak NT-proBNP levels exhibited no
      significant correlation with either pulmonary capillary wedge pressure or
      systolic wall stress. However, the peak NT-proBNP level correlated significantly
      with the simultaneous plasma normetanephrine concentrations (r = 0.53, p = 0.001)
      and the extent of impairment of LV systolic function, as measured by the wall
      motion score index (r = 0.37, p = 0.008) and LV ejection fraction (r = -0.39, p =
      0.008). In conclusion, TTC is associated with marked and persistent elevation of
      NT-proBNP/BNP levels, which correlated with both the extent of catecholamine
      increase and the severity of LV systolic dysfunction.

PMID- 21871588
TI  - Noise induced changes in the expression of p38/MAPK signaling proteins in the
      sensory epithelium of the inner ear.
AB  - Noise exposure is a major cause of hearing loss. Classical methods of studying
      protein involvement have provided a basis for understanding signaling pathways
      that mediate hearing loss and damage repair but do not lend themselves to
      studying large networks of proteins that are likely to increase or decrease
      during noise trauma. To address this issue, antibody microarrays were used to
      quantify the very early changes in protein expression in three distinct regions
      of the chinchilla cochlea 2h after exposure to a 0.5-8 kHz band of noise for 2h
      at 112 dB SPL. The noise exposure caused significant functional impairment 2h
      post-exposure which only partially recovered. Distortion product otoacoustic
      emissions were abolished 2h after the exposure, but at 4 weeks post-exposure,
      otoacoustic emissions were present, but still greatly depressed. Cochleograms
      obtained 4 weeks post-exposure demonstrated significant loss of outer hair cells
      in the basal 60% of the cochlea corresponding to frequencies in the noise
      spectrum. A comparative analysis of the very early (2h post-exposure) noise
      induced proteomic changes indicated that the sensory epithelium, lateral wall and
      modiolus differ in their biological response to noise. Bioinformatic analysis of
      the cochlear protein profile using "The Database for Annotation, Visualization
      and Integrated Discovery 2008" (DAVID - http://david.abcc. ncifcrf.gov) revealed
      the initiation of the cell death process in sensory epithelium and modiolus. An
      increase in Fas and phosphorylation of FAK and p38/MAPK in the sensory epithelium
      suggest that noise-induced stress signals at the cell membrane are transmitted to
      the nucleus by Fas and focal adhesion signaling through the p38/MAPK signaling
      pathway. Up-regulation of downstream nuclear proteins E2F3 and WSTF in
      immunoblots and microarrays along with their immunolocalization in the outer hair
      cells supported the pivotal role of p38/MAPK signaling in the mechanism
      underlying noise-induced hearing loss.

PMID- 21871591
TI  - Sex-specific threshold levels of plasma B-type natriuretic peptide for prediction
      of cardiovascular event risk in a Japanese population initially free of
      cardiovascular disease.
AB  - Elevated plasma B-type natriuretic peptide (BNP) levels have been reported to be
      related to a high risk for cardiovascular (CV) disease in the general population.
      However, there has been no accurate determination of the threshold levels of
      plasma BNP that indicate an increased potential for the development of general CV
      events (i.e., heart failure, stroke, and myocardial infarction) and the validity
      of these levels for predicting CV events compared to classic risk markers. To
      establish gender-specific thresholds of plasma BNP levels associated with
      increased risk for CV disease in the general population, baseline BNP levels were
      determined in community-dwelling adults (n = 13,209, mean age 62 +/- 10 years,)
      and CV events in the cohort were captured prospectively. The cohort was divided
      by deciles of plasma BNP level in each gender. A Cox proportional-hazards model
      was used to determine the relative hazard ratios among the deciles. In addition,
      to compare the utility of plasma BNP to the Framingham 10-year risk score for
      predicting general CV events, receiver-operating characteristic analysis was
      performed. During follow-up, CV events were identified in 429 patients in the
      cohort. Compared to the reference decile level (first to fourth), the hazard
      ratio was significantly increased from the ninth decile in men (greater than
      approximately 37 pg/ml) and the highest decile in women (greater than
      approximately 55 pg/ml). The area under the curve generated on receiver-operating
      characteristic analysis of plasma BNP testing was comparable to that for the
      Framingham risk scoring system (0.67 vs 0.68 in men, 0.63 vs 0.68 in women; p =
      NS for both). In conclusion, within a community-based general population with no
      CV history, plasma BNP levels higher than defined thresholds show increased risk
      for general CV events, and the predictive ability for CV events occurring within
      several years may be comparable to that of an established long-standing risk
      score.

PMID- 21871592
TI  - An assessment of the concentration-related prognostic value of cardiac troponin I
      following acute coronary syndrome.
AB  - In 2004 the British Cardiac Society redefined myocardial infarction by cardiac
      troponin I (cTnI) concentration: <= 0.06 MUg/L (unstable angina), >0.06 to < 0.5
      MUg/L (myocardial necrosis), and >= 0.5 MUg/L (myocardial infarction). We
      investigated the effects of this classification on all-cause mortality in 1,285
      patients from the Evaluation of the Methods and Management of Acute Coronary
      Events (EMMACE)-2 registry. There were 528 deaths (6.6-year all-cause mortality
      41.1%). Survival was greatest in the cTnI <= 0.06-MUg/L subgroup at 30 days (p =
      0.005), 6 months (p = 0.015), 1 year (p = 0.002), and 6.6 years (p = 0.045).
      After adjustment there was no significant difference in survival between the cTnI
      >0.06- to < 0.5-MUg/L and >= 0.5-MUg/L subgroups. Increased mortality (hazard
      ratio, 95% confidence interval) was associated with ages 70 to 80 years (2.58,
      1.17 to 3.91) and >80 years (3.30, 3.50 to 5.06), peripheral vascular disease
      (1.50, 1.16 to 1.94), heart failure (1.36, 1.05 to 1.83), diabetes mellitus
      (1.68, 1.36 to 2.07), severe left ventricular systolic dysfunction (1.50, 1.00 to
      2.21), and creatinine per 10 MUmol/L (1.65, 1.02 to 1.08), whereas ages 50 to 60
      years (0.55, 0.32 to 0.96), beta blockers (0.53, 0.44 to 0.64), aspirin (0.80
      0.65 to 0.99), angiotensin-converting enzyme inhibitors (0.67, 0.56 to 0.80),
      statins (0.73, 0.59 to 0.90), and revascularization (0.33, 0.12 to 0.92) were
      associated with a lower risk of death. In conclusion, although quantitative
      evaluation of cTnI concentration in patients with acute coronary syndrome with
      cTnI > 0.06 MUg/L was associated with no added prognostic information, the
      dichotomization of patients by cTnI status ("positive" and "negative")
      facilitates acute coronary syndrome risk stratification.

PMID- 21871593
TI  - Microvascular dysfunction in the spectrum of coronary instability.
AB  - The term "coronary instability" commonly refers to the sequence of events that
      lead from plaque erosion or rupture to the occurrence of acute coronary syndromes
      (ACS). However, evidence indicates that coronary microvascular dysfunction plays
      a relevant pathophysiologic and prognostic role in the setting of ACS, both in ST
      segment elevation myocardial infarction and in non-ST-segment elevation ACS. Our
      group have recently demonstrated that Tako-Tsubo syndrome, which clinically
      mimics ACS, is sustained by a common pathophysiologic mechanism represented by
      reversible coronary microvascular dysfunction. Given this evidence, we propose a
      reappraisal of the concept of coronary instability, extending this notion from
      the dramatic event represented by plaque erosion or rupture to a more diffuse
      process that can acutely affect each segment of the coronary circulation.

PMID- 21871594
TI  - Burden of systemic hypertension in patients admitted to cardiology
      hospitalization units.
AB  - Hypertension is 1 of the most prevalent cardiovascular risk factors;
      nevertheless, some studies have reported that the antecedent of hypertension does
      not impair prognosis in patients with established cardiovascular disease. The
      objective of this study was to describe the impact of hypertension on readmission
      and 1-year mortality in patients admitted to a single cardiology hospitalization
      unit. All consecutive hospitalizations in a single cardiology department through
      10 months were included, and 1-year follow-up was performed. Clinical
      antecedents, risk factors, and main discharge diagnoses were collected. A total
      of 1,007 patients were included (mean age 71.1 +/- 13.5 years). The antecedent of
      hypertension was present in 69.0%, and these patients had older mean age and
      higher prevalence of risk factors and previous cardiovascular disease. No
      differences in hospital discharge main diagnoses were observed according to the
      antecedent of hypertension. During a mean follow-up period of 404.82 +/- 122.2
      days, patients with hypertension had higher rates of rehospitalization for
      cardiac causes (31.1% vs 17.9%, p = 0.01) and of total (17.4% vs 9.3%, p <0.01)
      and cardiovascular (13.9% vs 5.9%, p <0.01) mortality. Multivariate analysis
      identified the antecedent of hypertension as an independent risk factor for
      cardiovascular readmission (hazard ratio 1.46, 95% confidence interval 1.10 to
      1.98) and the combined end point of readmission or mortality (hazard ratio 1.45,
      95% confidence interval 1.12 to 1.88); no independent association was observed
      for total mortality. In conclusion, hypertension was present in most patients
      admitted to a cardiology unit, and they had higher rates of rehospitalization and
      mortality at 1-year follow-up.

PMID- 21871596
TI  - Complementary telephone strategies to improve postdischarge communication.

PMID- 21871595
TI  - A variant in MCF2L is associated with osteoarthritis.
AB  - Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a
      substantial public health impact. We used a 1000-Genomes-Project-based imputation
      in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894
      controls) to detect a previously unidentified risk locus. We discovered a small
      disease-associated set of variants on chromosome 13. Through large-scale
      replication, we establish a robust association with SNPs in MCF2L (rs11842874,
      combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 * 10(-8))
      across a total of 19,041 OA cases and 24,504 controls of European descent. This
      risk locus represents the third established signal for OA overall. MCF2L
      regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal
      antibody against NGF is associated with reduction in pain and improvement in
      function for knee OA patients.

PMID- 21871598
TI  - Fetopathologic examination for early termination of pregnancy: dogma or
      necessity?
AB  - OBJECTIVE: Our objective was assessment of fetopathological examination after
      termination of pregnancy (TOP) for fetal anomalies with normal karyotype <17
      weeks of gestation. STUDY DESIGN: This was a multicenter retrospective study.
      Records of TOP for fetal anomalies with normal karyotype were analyzed. Primary
      outcomes were modifications of genetic counseling and management of next
      subsequent pregnancies. Medical TOPs were compared with surgical TOPs. RESULTS:
      In all, 59 pregnancies were included (30 aspirations, 29 inductions).
      Fetopathological examination modified genetic counseling for 22 patients: 62% for
      the medical induction group vs 13% in the vacuum aspiration group (P < .001).
      Management of subsequent pregnancies was modified in 17% in the medical induction
      group vs 3% in the aspiration group (P = .06). CONCLUSION: Fetopathological
      examination for early TOP with normal karyotype is relevant, especially when an
      intact fetus is examined. Thanks to it, genetic counseling is often modified, as
      is management of the next pregnancy. Medical procedures should be preferred to
      surgical procedures.

PMID- 21871597
TI  - Hydroxychloroquine reduces binding of antiphospholipid antibodies to
      syncytiotrophoblasts and restores annexin A5 expression.
AB  - OBJECTIVE: Antibody-mediated disruption of the annexin A5 anticoagulant shield
      has been posited to be a thrombogenic mechanism in the antiphospholipid syndrome.
      We recently showed that the antimalarial drug, hydroxychloroquine, dissociates
      antiphospholipid immune complexes and restores annexin A5 binding to planar
      phospholipid bilayer. Using quantitative immunoassays, we demonstrated similar
      effects on BeWo trophoblasts. We therefore, investigated the effects of the drug
      on localization of annexin A5 in primary cultures of human placental
      syncytiotrophoblasts. STUDY DESIGN: Laser confocal microscopy with computer-based
      morphometric analysis was used to localize annexin A5 and antiphospholipid
      antibodies on syncytiotrophoblasts exposed to polyclonal and monoclonal
      antiphospholipid and control immunoglobulin-Gs. RESULTS: Hydroxychloroquine
      reversed the effects of the antiphospholipid antibodies on the
      syncytiotrophoblasts by markedly reducing immunoglobulin-G binding and restoring
      annexin A5 expression. CONCLUSION: These results provide the first morphologic
      evidence for this effect of hydroxychloroquine on human placental
      syncytiotrophoblasts and support the possibility of novel treatments that target
      antiphospholipid antibody binding.

PMID- 21871599
TI  - The effect of iris-fixated foldable phakic intraocular lenses on retinal
      straylight.
AB  - PURPOSE: To determine changes in straylight after iris-fixated phakic intraocular
      lens implantation (pIOL) and to investigate the relationship between straylight
      and several preoperative and postoperative variables. DESIGN: Institutional,
      prospective cross-sectional study. METHODS: Artiflex (Ophtec B.V.) pIOL
      implantation was performed in 61 eyes (36 patients). Straylight values were
      measured before surgery and 3 months after surgery using the Oculus C-Quant
      (Oculus Optikgerate). Furthermore, correlations were analyzed between straylight
      and the following parameters: keratometry, axial length, spherical equivalent,
      astigmatism, pIOL power, best spectacle-corrected visual acuity, and pupil size.
      RESULTS: Mean straylight decreased from 1.18 +/- 0.17 log units before surgery to
      1.13 +/- 0.17 after surgery (P = .016). Higher preoperative straylight values
      were associated with larger postoperative decreases in straylight (r = -0.534; P
      < .001). Higher postoperative straylight values were correlated to higher axial
      length (r = 0.444; P = .001) and lower keratometry values in diopters (r = 
      0.414; P = .001). After regression analysis, only axial length was found to be an
      independent predictor of preoperative and postoperative straylight (P < .001 and
      P = .001, respectively). After correcting for the axial length of an emmetropic
      eye (23.44 mm), all straylight correlations disappeared, indicating that an
      increase in distance from cornea to retina explains the increase in straylight
      values in longer eyes. CONCLUSIONS: Retinal straylight was reduced significantly
      after Artiflex pIOL implantation. Besides age, axial length was the only
      predictor of preoperative and postoperative straylight values. The increased
      tissue length light has to pass from cornea to retina, might explain the increase
      in straylight values in longer eyes.

PMID- 21871600
TI  - The impact of contact lens wear and visual display terminal work on ocular
      surface and tear functions in office workers.
AB  - PURPOSE: To evaluate the effect of contact lens (CL) wear and visual display
      terminal (VDT) work on the ocular surface and tear functions. DESIGN: Prospective
      case-control study. METHODS: Sixty-nine CL wearers (45 women and 24 men; mean
      age, 35.2 +/- 7.3 years), and 102 age- and sex-matched non-CL wearers were
      enrolled in the study (66 women and 36 men; mean age, 36.7 +/- 7.3 years). Ocular
      surface and tear function tests, including vital stainings (fluorescein and rose
      bengal), Schirmer test, tear meniscus height measurement, and tear film break-up
      time were performed. The subjective symptoms of dry eyes were evaluated using a
      dry eye symptom questionnaire. The participants were divided into 4 subgroups
      according to the total time of VDT work in 1 day (VDT work time in 1 day >= 4
      hours or < 4 hours) and presence of CL wear. Main outcome measures included
      ocular surface vital staining scores, Schirmer test results, tear film break-up
      time, tear meniscus height measurement, and symptom questionnaire score. RESULTS:
      CL users and long-term VDT workers showed significantly worse tear meniscus
      height values than non-CL users and short-term VDT workers (P < .001). The mean
      visual symptom scores in CL wearers and long-term VDT workers were significantly
      higher than the other groups (P < .001). CONCLUSIONS: Office workers who wore CLs
      and spent more than 4 hours engaged in VDT work had a lower tear meniscus volume
      with significant dry eye and visual symptoms triggered by environmental factors.

PMID- 21871601
TI  - Lamellar keratoplasty and keratolimbal allograft for mustard gas keratitis.
AB  - PURPOSE: To report the clinical outcomes of lamellar keratoplasty (LKP) in
      patients with delayed-onset mustard gas keratitis and to compare visual acuity
      and graft survival rates between subgroups with simultaneous or sequential
      keratolimbal allograft and LKP. DESIGN: Retrospective, comparative,
      interventional case series. METHODS: Fifty-two eyes of 37 male survivors of
      chemical warfare with mustard gas keratitis who underwent LKP were included. The
      results were evaluated with respect to best spectacle-corrected visual acuity
      (BSCVA), refractive error and keratometry readings, and graft clarity. Thirty-two
      eyes required stem cell transplantation (keratolimbal allograft), which was
      performed before or concomitant with LKP. The groups with sequential and
      concomitant intervention were compared regarding BSCVA, refraction, corneal graft
      surface stability, and stem cell and corneal graft survival rates. RESULTS: The
      mean patient age at the time of surgery was 43.4 +/- 8.2 years, and the mean
      follow-up period was 41.4 +/- 19.6 months. The mean preoperative BSCVA was 0.51
      +/- 0.48 logarithm of the minimal angle of resolution units, which increased to
      0.33 +/- 0.18 logarithm of the minimal angle of resolution units (P = .03). The
      mean preoperative spherical equivalent refractive error was -2.40 +/- 1.5
      diopters, which remained unchanged after surgery (-1.52 +/- 3.7 diopters; P =
      .77). No significant difference between the sequential and simultaneous subgroups
      was found with regard to postoperative BSCVA, refraction, keratometry readings,
      or corneal graft survival (90.3% and 89.9%, respectively; P = .68). However, the
      latter group had statistically better stem cell graft survival (40.0% vs 100% at
      month 41, respectively; P = .02). CONCLUSIONS: LKP is an effective method of
      corneal transplantation in mustard gas victims. When stem cell and corneal
      transplantation are indicated, the simultaneous approach can yield better results
      than staged intervention.

PMID- 21871602
TI  - Laser-assisted in situ keratomileusis in high levels of myopia with the amaris
      excimer laser using optimized aspherical profiles.
AB  - PURPOSE: To evaluate the clinical outcomes of laser-assisted in situ
      keratomileusis (LASIK) surgery for the correction of high myopia using a new
      generation of excimer laser (500-Hz repetition rate) and optimized aspherical
      profiles. DESIGN: Retrospective interventional case series. METHODS:
      Retrospective study including 51 eyes of 32 patients (age range 23-61 years) with
      high levels of myopia or myopic astigmatism (spherical equivalent >=8.5 diopters
      [D]). All cases underwent uneventful LASIK surgery using the sixth-generation
      excimer laser Amaris from Schwind and a femtosecond platform for flap creation.
      Postoperative changes in visual acuity and refraction were recorded and analyzed
      during a 6-month follow-up. RESULTS: A significant improvement of about 15 logMAR
      lines was observed in uncorrected distance visual acuity (UCDVA) at 3 months
      after surgery (P < .01), with no significant changes afterwards (P = .61). This
      improvement was consistent with a significant reduction of manifest refraction (P
      < .01). Best corrected distance visual acuity (BCDVA) remained unchanged or
      improved in 98% of eyes at 3 months postoperatively, with only 1 eye losing 1
      logMAR line of BCDVA. A similar distribution of BCDVA data was observed at 6
      months postoperatively. A total of 84.3% of eyes had a postoperative spherical
      equivalent within +/-0.50 D of emmetropia. A limited but significant induction of
      primary spherical aberration and coma was also found (P < .01). LASIK enhancement
      was required during the follow-up in only 4 eyes (7.8%). CONCLUSIONS: LASIK for
      high myopia using optimized aspherical profiles and the Amaris excimer laser is a
      safe, effective, and predictable procedure.

PMID- 21871603
TI  - Assessment of corneal thickness and keratocyte density in a rabbit model of laser
      in situ keratomileusis using scanning laser confocal microscopy.
AB  - PURPOSE: To determine the repeatability of corneal thickness and keratocyte
      density using in vivo confocal scanning laser microscopy in a rabbit model of
      laser in situ keratomileusis. DESIGN: Prospective, experimental animal study.
      METHODS: En face tomographic images of corneal tissue were captured from 5 New
      Zealand white rabbits. Central corneal thickness was compared with conventional
      ultrasonic pachymetry. Keratocyte density was measured as a function of stromal
      depth at baseline and 6 weeks after a 130-MUm lamellar incision in the following
      regions: first countable stromal image (30 to 39 MUm), anterior stroma (40 to 75
      MUm), incision zone (76 to 150 MUm), mid stroma (151 to 250 MUm), and deep stroma
      (251 to 400 MUm). RESULTS: The mean residual difference between ultrasonic and
      confocal corneal thickness measurements was 2.1 MUm (95% confidence interval
      [CI], -7.0 to 11.2 MUm; P = .61). Before the lamellar incision, keratocyte
      density was highest in the first countable frame of the anterior stroma, 53 800
      cells/mm(3) (95% CI, 35 000 to 72 000 cells/mm(3)) and was least in deep stroma,
      27 100 cells/mm(3) (95% CI, 22 400 to 32 000 cells/mm(3)). Six weeks after
      stromal lamellar incision, keratocyte density was unchanged in the first
      countable frame of the anterior stroma, 43 700 cells/mm(3) (95% CI, 31 800 to 55
      500 cells/mm(3); P = .29). There were no changes in cell density in deeper
      stromal regions. CONCLUSIONS: There was excellent agreement between ultrasonic
      and confocal microscopy measurements of corneal thickness. In vivo repeatability
      of keratocyte density estimation using scanning laser confocal microscopy is
      comparable with the results of previous reports using tandem-scanning confocal
      microscopy. Keratocyte density was more varied, but not significantly different,
      in the anterior-most corneal stroma 6 weeks after a lamellar incision.

PMID- 21871604
TI  - Crossing safety barriers: influence of children's morphological and functional
      variables.
AB  - Thirty-three children between 3 and 6 years of age were asked to climb four
      different types of safety barriers. Morphological and functional variables of the
      children, which were expected to influence climbing or passing through skills,
      were collected. The influence of those variables on children's success rate and
      time to cross was tested. No barrier offered a total restraining efficacy. The
      horizontal bars barrier was crossed by 97% of the children. In the group of
      children that succeeded in crossing the four barriers, mean time to cross the
      most difficult barrier was 15 s. Age was the best predictor for success in
      crossing most barriers but morphology and strength were important predictors of
      time to cross. The influence of anthropometric variables in time to cross was
      dependent upon the characteristics of the barrier. A good design of safety
      barriers should consider children's age, morphology and strength.

PMID- 21871605
TI  - Driver usage and understanding of adaptive cruise control.
AB  - Automation, in terms of systems such as adaptive/active cruise control (ACC) or
      collision warning systems, is increasingly becoming a part of everyday driving.
      These systems are not perfect though, and the driver has to be prepared to
      reclaim control in situations very similar to those the system easily handles by
      itself. This paper uses a questionnaire answered by 130 ACC users to discuss
      future research needs in the area of driver assistance systems. Results show that
      the longer drivers use their systems, the more aware of its limitations they
      become. Moreover, the drivers report that ACC forces them to take control
      intermittently. According to theory, this might actually be better than a more
      perfect system, as it provides preparation for unexpected situations requiring
      the driver to reclaim control.

PMID- 21871606
TI  - Immunohistochemical analysis of bone resorption regulators (RANKL and OPG),
      angiogenic index, and myofibroblasts in syndrome and non-syndrome odontogenic
      keratocysts.
AB  - OBJECTIVE: The aim of this study was to immunohistochemically analyse bone
      resorption regulators (receptor activator of nuclear factor kappa B ligand
      [RANKL] and osteoprotegerin [OPG]), angiogenic index, and myofibroblasts in
      Gorlin syndrome-related odontogenic keratocysts (SOKCs) and non-syndrome
      odontogenic keratocysts (NSOKCs). STUDY DESIGN: Twenty-two SOKCs, 22 primary
      NSOKCs, and eight recurrent NSOKCs were evaluated by immunohistochemistry using
      anti-RANKL and anti-OPG antibodies. The angiogenic index was determined by
      microvessel count (MVC) using anti-CD34 antibody. Anti-alpha-smooth muscle actin
      (alpha-SMA) antibody was used for the identification of myofibroblasts. RESULTS:
      Analysis of the expression of RANKL and OPG in the epithelial lining and fibrous
      capsule did not reveal significant differences between groups (P>0.05). In the
      epithelial lining, the RANKL/OPG ratio was RANKL<OPG and RANKL=OPG in most
      primary NSOCKs (54.5%) and SOKCs (59.1%), respectively (P>0.05). In the fibrous
      capsule, the ratio was RANKL=OPG in most primary (81.8%) and recurrent NSOKCs
      (75.0%) and in most SOKCs (45.5%) (P>0.05). No significant differences in the
      angiogenic index or number of myofibroblasts were observed between primary
      NSOKCs, recurrent NSOKCs, and SOKCs (P>0.05). CONCLUSIONS: The present results
      suggest that differences in the biological behaviour of SOKCs and NSOKCs may not
      be related to the expression of RANKL and OPG, to the RANKL/OPG ratio, to the
      angiogenic index, or to the number of myofibroblasts in these lesions.

PMID- 21871607
TI  - Effects of boric acid on experimental periodontitis and alveolar bone loss in
      rats.
AB  - OBJECTIVE: The goal of the present study was to evaluate the histopathologic and
      morphometric effects of systemic boric acid in a rat periodontitis model. DESIGN:
      Twenty-four Wistar rats were divided into three groups of eight animals each: non
      ligated (NL), ligature only (LO), and ligature and treated with boric acid (BA)
      (3mg/kg per day for 11 days). A 4/0 silk suture was placed in a subgingival
      position around the mandibular first molars; after 11 days the rats were
      sacrificed, and changes in alveolar bone levels were measured clinically and
      tissues were histopathologically examined to assess the differences amongst the
      study groups. RESULTS: The ratio of presence of inflammatory cell infiltration
      (ICI) and osteoclast number in the LO group was significantly higher than that of
      the NL and BA groups (p<0.05). The ratio of presence of osteoblastic activity in
      the LO group was significantly lower than that of the NL and BA groups (p<0.05).
      Alveolar bone loss was also significantly higher in the LO group compared to the
      BA and NL groups (p<005). CONCLUSIONS: This study has demonstrated that systemic
      administration of boric acid reduced periodontal inflammation and alveolar bone
      loss in periodontal disease in rats.

PMID- 21871608
TI  - Attentional control in OCD and GAD: specificity and associations with core
      cognitive symptoms.
AB  - Obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) are
      both defined by excessive negatively-valenced cognitions. Although obsessional
      thoughts are considered essential to OCD and perseverative worry is considered
      essential to GAD, these excessive cognitions have been found to co-occur in both
      disorders. Accordingly, a common diathesis may influence the emergence of
      excessive thoughts in both disorders. The present study examined deficits in
      attentional control as a cognitive vulnerability that may contribute to both
      obsessional thought and perseverative worry. Patients with OCD (n=30), GAD
      (n=29), and non-clinical controls (NCC; n=29) completed measures of obsessional
      thoughts, perseverative worry, and attentional control. Deficits in self-reported
      attentional control were found in both OCD and GAD relative to the NCC. However,
      attentional control was only related to excessive cognition in the GAD patient
      group, where deficits were associated with increased perseverative worry.
      Mediational modeling suggested that trait anxiety mediated the relationship
      between attentional control and perseverative worry in GAD. Implications of these
      findings for conceptualizing the role of attentional control in the genesis of
      excessive cognitions in OCD and GAD are discussed.

PMID- 21871611
TI  - Event-related brain responses as correlates of changes in predictive and
      affective values of conditioned stimuli.
AB  - Previous evidence suggests that the judged predictive strength of one cue may be
      influenced by the predictive strengths of other pretrained cues (prediction
      errors). In the present study, we examined affective ratings and event-related
      brain responses from 18 healthy participants during an aversive conditioning task
      in which affective values of previously trained conditioned stimuli were modified
      through a blocking procedure. The task was divided into two phases. During the
      training phase, single stimulus A (e.g., red square) was always followed by
      aversive picture stimuli, while single stimulus B (e.g., yellow square) was
      signaling the absence of aversive stimulation. During the blocking phase,
      compound stimuli consisted of the combination of one single trained stimulus (A
      or B) and one new somatosensory stimulus were also followed by the presence of
      aversive stimulation. Results indicated that single stimulus A elicited greater
      ERP amplitudes and theta power, and was rated as more unpleasant than single
      stimulus B during the training phase. Moreover, single stimulus B elicited
      greater ERP amplitudes than stimulus A, as well as greater theta power and more
      unpleasant ratings during the blocking as compared with the training phase. By
      contrast, no changes in ERP amplitudes and theta power were observed for stimulus
      A. Our findings provide neurophysiological and behavioral evidence for an
      increased affective processing of conditioned stimuli when compound stimuli were
      introduced, but only if the target CS was previously trained to signal the
      absence of aversive stimulation.

PMID- 21871609
TI  - Prioritization and association analysis of murine-derived candidate genes in
      anxiety-spectrum disorders.
AB  - BACKGROUND: Anxiety disorders are common psychiatric conditions that are highly
      comorbid with each other and related phenotypes such as depression, likely due to
      a shared genetic basis. Fear-related behaviors in mice have long been
      investigated as potential models of anxiety disorders, making integration of
      information from both murine and human genetic data a powerful strategy for
      identifying potential susceptibility genes for these conditions. METHODS: We
      combined genome-wide association analysis of fear-related behaviors with strain
      distribution pattern analysis in heterogeneous stock mice to identify a
      preliminary list of 52 novel candidate genes. We ranked these according to three
      complementary sources of prior anxiety-related genetic data: 1) extant linkage
      and knockout studies in mice, 2) a meta-analysis of human linkage scans, and 3) a
      preliminary human genome-wide association study. We genotyped tagging single
      nucleotide polymorphisms covering the nine top-ranked regions in a two-stage
      association study of 1316 subjects from the Virginia Adult Twin Study of
      Psychiatric and Substance Use Disorders chosen for high or low genetic loading
      for anxiety-spectrum phenotypes (anxiety disorders, neuroticism, and major
      depression). RESULTS: Multiple single nucleotide polymorphisms in the PPARGC1A
      gene demonstrated association in both stages that survived gene-wise correction
      for multiple testing. CONCLUSIONS: Integration of genetic data across human and
      murine studies suggests PPARGC1A as a potential susceptibility gene for anxiety
      related disorders.

PMID- 21871612
TI  - Age-related differences in performance and stimulus processing in dual task
      situation.
AB  - Competition for limited processing resources is most critical in dual-tasks which
      incorporate cognitive and motor demands. Performance is usually diminished with
      increasing age in such tasks. This decline is relevant for activities in real
      life like driving. In the present study we aim to examine if there are age
      related differences in stimulus processing in a dual-task and if these
      differences have an impact on performance of a driving-like tracking task. Young
      and older participants performed a dual-task consisting of a tracking task and a
      visual attention task. Alongside, the EEG was recorded for calculating the P300
      (P3) of the event-related potential as a reflection of controlled stimulus
      processing. In the visual attention task older vs. young participants showed more
      misses and false alarms. For young participants the P3 shows an expected pattern
      of higher amplitudes for relevant compared to irrelevant stimuli. This was not
      found for the older participants. A general age-related decline in tracking
      performance was relatively more pronounced if a secondary motor response was
      required in the visual attention task and also after irrelevant stimuli. The
      results suggest that older compared to young participants had greater
      difficulties to differentiate between relevant and irrelevant stimuli in a dual
      task situation as they probably apply comparable attentional resources to all
      stimuli. This may also explain the higher error rates. These results have
      important implications for the understanding of age-related stimulus processing
      in dual and multi task situations in real life as for instance driving.

PMID- 21871610
TI  - CART peptide following social novelty in the prairie vole (Microtus ochrogaster).
AB  - Prairie voles (Microtus ochrogaster) are monogamous rodents that display high
      levels of affiliative behaviors, including pair-bonding, biparental care, and
      cooperative breeding. Species differences in basal cocaine- and amphetamine
      regulated transcript (CART) mRNA and peptide expression have been found between
      prairie voles and polygamous meadow voles. Therefore, we hypothesized that the
      CART system may play a role in the regulation of social behavior in this species.
      Male and female adult prairie voles were placed in a cage either alone, or with a
      novel social partner of the same or opposite sex. After 45 min, subjects were
      sacrificed and CART peptide expression was examined using immunohistochemistry.
      We examined fifteen hypothalamic, limbic, and hindbrain regions of interest,
      focusing on areas that show species-specific patterns of expression. We found
      that subjects paired with a novel conspecific had lower levels of peptide in the
      bed nucleus of the stria terminalis (BNST) than isolated animals. This may
      reflect increased peptide release following increased dopaminergic activity in
      animals exposed to a novel conspecific. Additionally, CART peptide was higher in
      the nucleus accumbens (NAc) of subjects paired with an opposite sex partner
      compared to those paired with a same-sex conspecific, although there was no
      difference between isolated subjects and either socially housed group. These
      findings suggest that CART in the NAc is differentially responsive to the sex of
      adult conspecifics and that the social environment influences CART expression in
      the prairie vole in a region- and stimulus-specific manner.

PMID- 21871613
TI  - Attenuated neurological deficit, cell death and lesion volume in Fas-mutant mice
      is associated with altered neuroinflammation following traumatic brain injury.
AB  - Progressive neurodegeneration following traumatic brain injury (TBI) involves the
      Fas and TNF-receptor1 protein systems which have been implicated in mediating
      delayed cell death. In this study, we used two approaches to assess whether
      inhibition of these pathways reduced secondary brain damage and neurological
      deficits after TBI. Firstly, we investigated whether the expression of non
      functional Fas in lpr mice subjected to TBI altered tissue damage and
      neurological outcome. Compared to wild-type, lpr mice showed improved
      neurological deficit (p=0.0009), decreased lesion volume (p=0.017), number of
      TUNEL+ cells (p=0.011) and caspase-3+ cells (p=0.007). Changes in cellular
      inflammation and cytokine production were also compared between mouse strains.
      Accumulation of macrophages/microglia occurred earlier in lpr mice, likely due to
      enhanced production of the chemotactic mediators IL-12(p40) and MCP-1 (p<0.05).
      Cortical production of IL-1alpha and IL-6 increased after injury to a similar
      extent regardless of strain (p<0.05), while TNF and G-CSF were significantly
      higher in lpr animals (p<0.05). Secondly, we assessed whether therapeutic
      inhibition of FasL and TNF via intravenous injection of neutralizing antibodies
      in wild-type mice post-TBI could reproduce the beneficial effects observed in lpr
      animals. No differences were found with this approach in animals treated with
      anti-FasL and anti-TNF antibodies alone or the combination of both. Altogether,
      reduced neurological deficits and lesion volume in lpr mice was associated with
      altered cellular and humoral inflammation, possibly contributing to
      neuroprotection, whereas neutralization of FasL and TNF had no effect. In future
      studies, the lpr mouse strain may be utilized as a model to further characterize
      molecular and cellular mechanisms protecting against secondary brain damage after
      TBI.

PMID- 21871614
TI  - beta1-adrenergic receptor up-regulation induced by nadolol is mediated via signal
      transduction pathway coupled to alpha1-adrenergic receptors.
AB  - Although up-regulation of beta-adrenergic receptors (beta-ARs) occurs after long
      term use of their antagonists in various tissues, the available data are little
      on mechanisms of beta-AR up-regulation induced by their continuous blockade. The
      present study attempted to clarify mechanisms of beta-AR up-regulation using
      mouse cerebral cortical neurons continuously exposed to nadolol (10 nM), a non
      selective beta-AR antagonist, for 24 h. Nadolol dose-dependently induced both
      subtypes of beta-ARs, beta1- and beta2-ARs, which were not suppressed by protein
      A kinase inhibition with KT5720. On the other hand, blockade of alpha1-ARs, which
      are immunohistochemically confirmed to be co-localized with beta-ARs in the same
      neurons, significantly inhibited only beta1-AR up-regulation and the expression
      of beta2-ARs did not alter. In addition, phenylephrine, an agonist specific to
      alpha1-ARs up-regulated beta1-ARs, but not beta2-ARs. Under the conditions with
      beta-AR up-regulation, the level of phosphorylated protein kinase Calpha
      (pPKCalpha) increased, which is significantly suppressed by prazosin, an alpha1
      AR antagonist. Furthermore, nadolol decreased the degradation of mRNA of beta1
      ARs, but not beta2-ARs. These results indicate that the nadolol-induced beta1-AR
      up-regulation is mediated via PKC-relating pathway via alpha1-AR activation with
      stabilizing beta1-AR mRNA and that the increased expression of beta2-ARs is
      regulated by pathways different from those for beta1-AR expression.

PMID- 21871615
TI  - [Adverse events in general surgery. A prospective analysis of 13,950 consecutive
      patients].
AB  - INTRODUCTION: Adverse event (AE) rates in General Surgery vary, according to
      different authors and recording methods, between 2% and 30%. Six years ago we
      designed a prospective AE recording system to change patient safety culture in
      our Department. We present the results of this work after a 6 year follow-up.
      MATERIAL AND METHOD: The AE, sequelae and health care errors in a University
      Hospital surgery department were recorded. An analysis of each incident recorded
      was performed by a reviewer. The data was entered into data base for rapid access
      and consultation. The results were routinely presented in Departmental morbidity
      mortality sessions. RESULTS: A total of 13,950 patients had suffered 11,254 AE,
      which affected 5142 of them (36.9% of admissions). A total of 920 patients were
      subjected to at least one health care error (6.6% of admissions). This meant that
      6.6% of our patients suffered an avoidable AE. The overall mortality at 5 years
      in our department was 2.72% (380 deaths). An adverse event was implicated in the
      death of the patient in 180 cases (1.29% of admissions). In 49 cases (0.35% of
      admissions), mortality could be attributed to an avoidable AE. After 6 years
      there tends to be an increasingly lower incidence of errors. CONCLUSIONS: The
      exhaustive and prospective recording of AE leads to changes in patient safety
      culture in a Surgery Department and helps decrease the incidence of health care
      errors.

PMID- 21871616
TI  - Depression and quality of life in first-episode psychosis.
AB  - AIM: Quality of life (QOL) has gained recognition as a valid measure of outcome
      in first-episode psychosis (FEP). This study aimed to determine the influence of
      specific groups of depressive symptoms on separate domains of subjectively
      appraised QOL. METHODS: We assessed 208 individuals with first-episode non
      affective psychosis using measures of diagnosis (Structured Clinical Interview
      for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition),
      symptoms (Scale for the Assessment of Positive Symptoms, Scale for the Assessment
      of Negative Symptoms, and Calgary Depression Scale for Schizophrenia),
      functioning (Global Assessment of Functioning), insight (Birchwood Scale),
      duration of untreated psychosis (Beiser Scale), and QOL World Health Organisation
      Quality of Life Instrument (WHOQOL-Bref). We used multiple regression to
      determine the contribution of depressive symptoms to QOL domains while
      controlling for socio-demographic and other clinical characteristics. RESULTS:
      There were complete data for 146 individuals with FEP. Quality-of-life domains
      were consistently predicted by depressive symptoms including depressive mood and
      hopelessness rather than biological symptoms of depression with those
      experiencing more depressive symptoms reporting worse QOL. Those who were treated
      as in-patients reported improved QOL, and hospitalization was an independent
      predictor of most QOL domains. In-patients displayed greater levels of positive
      symptoms with those involuntarily detained displaying greater levels of bizarre
      behavior, thought disorder, and delusions. CONCLUSIONS: These findings suggest
      that QOL is heavily influenced by depressive symptoms at initial presentation;
      however, as QOL domains are also influenced by admission status with in-patients
      being more symptomatic in terms of positive symptoms, subjective QOL assessment
      may be compromised during the acute phase of illness by both positive and
      depressive symptom severity.

PMID- 21871617
TI  - The association between anomalous self-experience and suicidality in first
      episode schizophrenia seems mediated by depression.
AB  - BACKGROUND: A recent hypothesis is that suicidality in schizophrenia may be
      linked to the patients' altered basic self-awareness or sense of self, termed
      self-disorders (SDs). AIM: The aim of the study was to investigate whether SDs in
      first-episode schizophrenia spectrum disorders are related to suicidality and
      whether this relationship is independent of or mediated by depression or other
      standard clinical measures. METHOD: Self-disorders were assessed in 49 patients
      with first-episode schizophrenia by means of the Examination of Anomalous Self
      Experience (EASE) instrument. Symptoms severity and functioning were assessed
      using the Structured Clinical Interview for the Positive and Negative Syndrome
      Scale, Calgary Depression Scale for Schizophrenia, and Global Assessment of
      Functioning-Split Version. Suicidality was measured by the Calgary Depression
      Scale for Schizophrenia item 8. RESULTS: Analyses detected a significant
      association between current suicidality, current depression, and SDs as measured
      by the EASE. The effect of SDs on suicidal ideation appeared to be mediated by
      depression. CONCLUSION: The interaction between anomalous self-experiences and
      depression could be a rational clinical target for the prevention of suicidality
      in the early phases of schizophrenia and supports the rationale for including
      assessment of SDs in early intervention efforts.

PMID- 21871618
TI  - Modeling of tumor growth undergoing virotherapy.
AB  - Tumor growth models subject to virotherapy treatment are analyzed and compared in
      this paper. Tumor growth conditions are obtained for each model type based on the
      virus infection rate and immune suppressive drug delivery. Equilibrium conditions
      resulted into quadratic functions for which the tumor radius remained constant
      during virotherapy. An irrigation tumor model for virotherapy treatment was also
      proposed. This model consists of irrigation layers distributed radially along the
      tumor and attached to a common blood circulation compartment. The irrigation
      model has similar dynamic and steady state characteristics to the diffusion
      model, which has been supported by experimental results. The irrigation model
      considers the immune system cell generation and consumption outside the tumor
      boundary but inside the blood circulation compartment. These characteristics
      provide a great potential for advanced cancer treatment applications because
      therapy dose delivery and immune system measurements can be made at the blood
      compartment level of the irrigation model.

PMID- 21871619
TI  - Differences in urine cadmium associations with kidney outcomes based on serum
      creatinine and cystatin C.
AB  - Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for
      chronic kidney disease. Recently, however, associations between urine cadmium and
      higher creatinine-based estimated glomerular filtration rate (eGFR) have been
      reported. Analyses utilizing alternate biomarkers of kidney function allow
      evaluation of potential mechanisms for these observations. We compared
      associations of urine cadmium with kidney function measures based on serum
      cystatin C to those with serum creatinine in 712 lead workers. Mean (standard
      deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal
      Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) MUg/g
      creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The
      eGFR measures were moderately correlated (rs=0.5; p<0.001). After adjustment, ln
      (urine cadmium) was not associated with serum cystatin-C-based measures. However,
      higher ln (urine cadmium) was associated with higher creatinine-based eGFRs
      including the MDRD and an equation incorporating serum cystatin C and creatinine
      (beta-coefficient=4.1 mL/min/1.73 m2; 95% confidence interval=1.6, 6.6). Urine
      creatinine was associated with serum creatinine-based but not cystatin-C-based
      eGFRs. These results support a biomarker-specific, rather than a kidney function,
      effect underlying the associations observed between higher urine cadmium and
      creatinine-based kidney function measures. Given the routine use of serum and
      urine creatinine in kidney and biomarker research, additional research to
      elucidate the mechanism(s) for these associations is essential.

PMID- 21871620
TI  - Ultrasound-guided transcervical evacuation of interstitial twin pregnancy.
AB  - OBJECTIVE: To report the transcervical and transisthmic evacuation of a
      dichorionic interstitial twin pregnancy guided by ultrasound. DESIGN: Case study.
      SETTING: Fetal medicine unit of university hospital. PATIENT(S): Dichorionic twin
      fetuses. INTERVENTION(S): Three-dimensional/four-dimensional (3D/4D) ultrasound
      guided transcervical and transisthmic evacuation under direct laparoscopic
      supervision. MAIN OUTCOME MEASURE(S): Maternal clinical outcome. RESULT(S): A
      dichorionic interstitial twin pregnancy was successfully evacuated without
      complications. CONCLUSION(S): The safety and effectiveness of ultrasound-guided
      transcervical and transisthmic evacuation of dichorionic interstitial twin
      pregnancy warrants further evaluation.

PMID- 21871621
TI  - Sperm fluorescence in situ hybridization study in nine men carrying a
      Robertsonian or a reciprocal translocation: relationship between segregation
      modes and high-magnification sperm morphology examination.
AB  - OBJECTIVE: To evaluate whether observation of spermatozoa at * 6,100
      magnification can distinguish between those with and without a balanced
      chromosomal content. DESIGN: Retrospective research study. SETTING: Genetics
      laboratory of a university hospital and in vitro fertilization center.
      PATIENT(S): Six men carrying a reciprocal translocation and three men with a
      Robertsonian translocation. INTERVENTION(S): Sperm fluorescence in situ
      hybridization (FISH) with a specific set of three probes for each translocation
      for determining chromosomal content, performed on both unselected spermatozoa and
      on spermatozoa selected at * 6,100 magnification according to the Cassuto-Barak
      classification. MAIN OUTCOME MEASURE(S): Chromosomal content in unselected and
      selected spermatozoa. RESULT(S): Chromosomal translocations lead to gametes
      carrying either a balanced or an unbalanced karyotype in offspring and
      consequently to changes in chromosome position within sperm nucleus and
      potentially in nuclear morphology. In the unselected spermatozoa, the rate of
      chromosomally balanced nuclei ranged from 37.1% to 52.6% and from 70% to 88.6% in
      reciprocal and Robertsonian translocations, respectively, which is in agreement
      with published data. In selected spermatozoa, there was no statistically
      significant difference between the rates of segregation modes when compared with
      their frequencies in unselected sperm cells. CONCLUSION(S): The observation of
      spermatozoa at high-magnification in translocation carriers cannot be used to
      select sperm cells with a balanced chromosomal content.

PMID- 21871622
TI  - Sperm DNA damage and seminal oxidative status after shock-wave lithotripsy for
      distal ureteral stones.
AB  - OBJECTIVE: To investigate the relationship between level of sperm DNA damage,
      seminal oxidative status, and shock-wave lithotripsy (SWL) for distal ureteral
      stones. DESIGN: Prospective study with control. SETTING: Academic research
      institute. PATIENT(S): Men who had undergone SWL for distal and upper ureter
      stones. INTERVENTION(S): Level of sperm DNA damage and seminal oxidative status
      assessed through the examination of semen on the day before and 3 days, and 3
      months after SWL. MAIN OUTCOME MEASURE(S): DNA damage score and oxidative stress
      in semen parameters. RESULT(S): Sperm DNA damage score and semen total oxidant
      status (TOS) levels increased, but semen total antioxidant status (TAS) levels,
      sperm concentration, and motility decreased immediately after SWL. However, there
      were no statistically significant correlations between the DNA damage scores and
      the increased TAS and TOS levels in the study group. All of the changes returned
      completely to initial level during three months after SWL. CONCLUSION(S): SWL may
      affect fertility in men. Therefore, we suggest other treatment modalities, such
      as ureteroscopy, for young men with distal ureteral stones to prevent the
      development of male infertility.

PMID- 21871623
TI  - Arterial pulse wave velocity in relation to carotid intima-media thickness,
      brachial flow-mediated dilation and carotid artery distensibility: the
      Cardiovascular Risk in Young Finns Study and the Health 2000 Survey.
AB  - OBJECTIVE: Increased arterial pulse wave velocity (PWV) is a strong predictor of
      cardiovascular events and mortality. The data regarding the relationships between
      PWV and other indices of vascular damage is limited and partly controversial. We
      conducted the present study to examine PWV in relation to non-invasive measures
      of early atherosclerosis (brachial flow-mediated dilation [FMD], carotid intima
      media thickness [IMT]) and local arterial stiffness (carotid artery
      distensibility [Cdist]). METHODS: The study population consisted of 1754 young
      adults (aged 30-45 years, 45.5% males) participating in the Cardiovascular Risk
      in Young Finns Study (YFS), and of 336 older adults (aged 46-76 years, 43.2%
      males) participating in the Health 2000 Survey. FMD was measured only in the YFS
      cohort. FMD, IMT and Cdist were assessed by ultrasound, and PWV was measured
      using the whole-body impedance cardiography device. RESULTS: In young adults, FMD
      and IMT were not associated with PWV independently of cardiovascular risk
      factors. Moreover, FMD status was not found to modulate the association between
      cardiovascular risk factors and PWV. In older adults, PWV and IMT were directly
      and independently associated (beta=1.233, p=0.019). In both cohorts, PWV was
      inversely related with Cdist, and this relation remained significant (p<0.04) in
      models adjusted for cardiovascular risk factors. CONCLUSIONS: The current
      findings suggest that PWV reflects a different aspect of vascular damage than FMD
      or IMT in young adults, whereas in older adults the information provided by PWV
      and IMT may be, to some extent, similar as regards subclinical vascular damage.
      The present observations also suggest that PWV and Cdist represent, at least in
      part, a similar adverse vascular wall process.

PMID- 21871624
TI  - Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6
      and cardiovascular risk and efficacy of atorvastatin among subjects with diabetes
      on dialysis: the 4D study.
AB  - AIMS: We investigated whether KIF6 Trp719Arg genotypes affect cardiovascular
      outcomes and efficacy of statin therapy in patients with type 2 diabetes mellitus
      undergoing hemodialysis. METHODS AND RESULTS: We conducted a post hoc analysis of
      the 4D-study, a randomized trial including 1255 patients. Patients were randomly
      assigned to double-blind treatment with either 20mg of atorvastatin (n = 619) or
      placebo (n = 636) once daily and followed for 4 years (median). DNA was available
      for 1232 patients and we assessed KIF6 Trp719Arg genotypes by PCR and subsequent
      restriction digest. Carriers of the Arg719 allele showed no increased prevalence
      of cardiovascular disease. The incidence of cardiac death, MI, and stroke did not
      differ across KIF6 genotypes, irrespective of whether the patients were treated
      with atorvastatin or not. CONCLUSION: In patients with type 2 diabetes mellitus
      on hemodialysis, KIF6 Trp719Arg genotypes were not associated with adverse
      cardiovascular outcomes during follow-up or with the efficacy of atorvastatin
      therapy.

PMID- 21871625
TI  - Fast, low-pressure gas chromatography triple quadrupole tandem mass spectrometry
      for analysis of 150 pesticide residues in fruits and vegetables.
AB  - We developed and evaluated a new method of low-pressure gas chromatography-tandem
      mass spectrometry (LP-GC/MS-MS) using a triple quadrupole instrument for fast
      analysis of 150 relevant pesticides in four representative fruits and vegetables.
      This LP-GC (vacuum outlet) approach entails coupling a 10 m, 0.53 mm i.d., 1 MUm
      film analytical column between the MS transfer line and a 3 m, 0.15 mm i.d.
      capillary at the inlet. The MS creates a vacuum in the 10 m analytical column,
      which reduces the viscosity of the He carrier gas and thereby shifts the optimal
      flow rate to greater velocity. By taking advantage of the H(2)-like properties of
      He under vacuum, the short analytical column, a rapid oven temperature ramp rate,
      and the high selectivity and sensitivity of MS/MS, 150 pesticides were separated
      in <6.5 min. The 2.5 ms dwell time and 1 ms interscan delay of the MS/MS
      instrument were critical for achieving >8 data points across the 2-3 s wide
      peaks. To keep dwell and cycle times constant across all peaks, each segment
      consisted of 30 analytes (60 transitions). For assessment, we injected extracts
      of spiked broccoli, cantaloupe, lemon, and sweet potato from the updated QuEChERS
      sample preparation method. Average recoveries (n=72) were 70-120% for 144 of the
      pesticides, and reproducibilities were <20% RSD for all but 4 analytes. Also,
      detection limits were <5 ng/g for all but a few pesticides, depending on the
      matrix. In addition to high quality performance, the method gave excellent
      reliability and high sample throughput, including easy peak integration to obtain
      rapid results.

PMID- 21871626
TI  - Methods for determination of all binding parameters in systems with simultaneous
      borate and cyclodextrin complexation.
AB  - Two novel methods for determination of binding constants in the systems with
      borate and cyclodextrin complexation were developed. The methods enable to
      determine all binding parameters in these systems and even the binding constants
      of interaction of a neutral analyte with a neutral cyclodextrin. The first method
      is based on nonlinear fitting of experimental data and further evaluation of
      fitting parameters. The second method requires a multiple regression. The methods
      provide identical results with low experimental error. Only one set of
      measurements is required for both methods. Thus the binding parameters can be
      mutually compared. The binding parameters for neutral analytes ((R,R)-(+)
      hydrobenzoin and (S,S)-(-)-hydrobenzoin) and neutral cyclodextrin (heptakis(2,6
      di-O-methyl)-beta-cyclodextrin) were evaluated and the effect of individual types
      of interaction was revealed. The interaction of the analytes with cyclodextrin
      governs the chiral recognition, while the complexation of analyte with borate is
      responsible for electromigration. Very low values of the binding constants of
      mixed analyte-cyclodextrin-borate complexes indicate that this type of
      complexation has negligible effect on enantioseparation.

PMID- 21871627
TI  - Comparison of two algorithmic data processing strategies for metabolic
      fingerprinting by comprehensive two-dimensional gas chromatography-time-of-flight
      mass spectrometry.
AB  - The alignment algorithm Statistical Compare (SC) developed by LECO Corporation
      for the processing of comprehensive two-dimensional gas chromatography-time-of
      flight mass spectrometry (GC*GC-TOFMS) data was validated and compared to the in
      house developed retention time correction and data alignment tool INCA
      (Integrative Normalization and Comparative Analysis) by a spike-in experiment and
      the comparative metabolic fingerprinting of a wild type versus a double mutant
      strain of Escherichia coli (E. coli). Starting with the same peak lists generated
      by LECO's ChromaTOF software, the accuracy of peak alignment and detection of 1.1
      to 4-fold changes in metabolite concentration was assessed by spiking 20
      standard compounds into an aqueous methanol extract of E. coli. To provide the
      same quality input signals for both alignment routines, the universal m/z 73
      trace of the trimethylsilyl (TMS) group was used as a quantitative measure for
      all features. The performance of data processing and alignment was evaluated and
      illustrated by ROC curves. Statistical Compare performed marginally better at the
      lower fold changes, while INCA did so at the higher fold changes. Using SC,
      quantitative precision could be improved substantially by exploiting the signal
      intensities of metabolite-specific unique (U) m/z ion traces rather than the
      universal m/z 73 trace. A list of 56 features that distinguished the two E. coli
      strains was obtained by the SC alignment using m/z U with an estimated false
      discovery rate (FDR) of <0.05. Ultimately, 23 metabolites could be identified,
      one additional and five less than with INCA due to the failure of SC to extract
      unitized m/z U's across all fingerprints with suitable spectral intensities for
      the latter metabolites.

PMID- 21871628
TI  - Synthesis and chromatographic evaluation of molecularly imprinted polymers
      prepared by the substructure approach for the class-selective recognition of
      glucuronides.
AB  - Two series of molecularly imprinted polymers (MIPs) for the class-selective
      recognition of glucuronides have been prepared by using lipophilic substructures
      of the target analyte as template molecule and potent host monomers against
      oxyanions, that are expected to establish a strong stoichiometric interaction
      with the single carboxylic group of the template. The polymers were tested as
      stationary phases in liquid chromatography for specific recognition. A
      preliminary investigation of the imprinting properties of eleven MIPs was carried
      out, by comparing the retention time of the template and of structurally related
      compounds on the MIP column with that on the corresponding non-imprinted polymer
      (NIP). The two polymers showing the best performance were selected to further
      test cotinine, mycophenolic acid, testosterone and their respective glucuronides
      as model compounds. The high specificity obtained against glucuronides and the
      different chemical structure of the parent drug make the two MIPs class-selective
      imprinted receptors, also suitable for SPE application.

PMID- 21871629
TI  - Determination of 3-methyl-2,4-nonanedione in red wines using methanol chemical
      ionization ion trap mass spectrometry.
AB  - A compound associated with oxidized flavor in red wines was recently-identified
      as 3-methyl-2,4-nonanedione (MND). In order to quantify it, positive chemical
      ionization (PCI) in an ion trap was studied using conventional liquid reagents
      such as methanol, acetonitrile, and acetone, as well as non-conventional liquid
      reagents such as ethyl acetate, diethyl ether, pentane, isohexane, and heptane.
      Under laboratory conditions, very different response factors were obtained with
      MND depending on the gas. We also compared the detection limit of conventional CI
      with hybrid chemical ionization (HCI). Finally, this compound was quantified in
      red wines by liquid/liquid extraction without any derivatization steps, followed
      by GC/MS-CI analysis, using methanol as the reagent gas. Coelutions of compounds
      with the same m/z were checked using methanol-d(4). The method we developed was
      linear in the 10-300 ng/L range of MND concentrations, with satisfactory
      repeatability. The detection limit was 4.3 ng/L, over 3 times lower than the
      olfactory perception threshold of this compound (16 ng/L). The suitability of
      this method for assaying this diketone in red wine was demonstrated by the
      analyzing many wines from different vintages.

PMID- 21871630
TI  - Exploration of overloaded cation exchange chromatography for monoclonal antibody
      purification.
AB  - Cation exchange chromatography using conventional resins, having either diffusive
      or perfusive flow paths, operated in bind-elute mode has been commonly employed
      in monoclonal antibody (MAb) purification processes. In this study, the
      performance of diffusive and perfusive cation exchange resins (SP-Sepharose FF
      (SPSFF) and Poros 50HS) and a convective cation exchange membrane (Mustang S) and
      monolith (SO(3) Monolith) were compared. All matrices were utilized in an
      isocratic state under typical binding conditions with an antibody load of up to
      1000 g/L of chromatographic matrix. The dynamic binding capacity of the cation
      exchange resins is typically below 100 g/L resin, so they were loaded beyond the
      point of anticipated MAb break through. All of the matrices performed similarly
      in that they effectively retained host cell protein and DNA during the loading
      and wash steps, while antibody flowed through each matrix after its dynamic
      binding capacity was reached. The matrices differed, though, in that conventional
      diffusive and perfusive chromatographic resins (SPSFF and Poros 50HS)
      demonstrated a higher binding capacity for high molecular weight species (HMW)
      than convective flow matrices (membrane and monolith); Poros 50HS displayed the
      highest HMW binding capacity. Further exploration of the conventional
      chromatographic resins in an isocratic overloaded mode demonstrated that the
      impurity binding capacity was well maintained on Poros 50HS, but not on SPSFF,
      when the operating flow rate was as high as 36 column volumes per hour. Host cell
      protein and HMW removal by Poros 50HS was affected by altering the loading
      conductivity. A higher percentage of host cell protein removal was achieved at a
      low conductivity of 3 mS/cm. HMW binding capacity was optimized at 5 mS/cm. Our
      data from runs on Poros 50HS resin also showed that leached protein A and cell
      culture additive such as gentamicin were able to be removed under the isocratic
      overloaded condition. Lastly, a MAb purification process employing protein A
      affinity chromatography, isocratic overloaded cation exchange chromatography
      using Poros 50HS and anion exchange chromatography using QSFF in flow through
      mode was compared with the MAb's commercial manufacturing process, which
      consisted of protein A affinity chromatography, cation exchange chromatography
      using SPSFF in bind-elute mode and anion exchange chromatography using QSFF in
      flow through mode. Comparable step yield and impurity clearance were obtained by
      the two processes.

PMID- 21871631
TI  - Tools to discover anionic and nonionic polyfluorinated alkyl surfactants by
      liquid chromatography electrospray ionisation mass spectrometry.
AB  - A tiered approach is proposed for the discovery of unknown anionic and nonionic
      polyfluorinated alkyl surfactants (PFASs) by reversed phase ultra high
      performance liquid chromatography (UHPLC)--negative electrospray ionisation-
      quadrupole time of flight mass spectrometry (UHPLC-ESI(-)-QTOF-MS). The
      chromatographic separation, ionisation and detection of PFASs mixtures, was
      achieved at high pH (pH=9.7) with NH(4)OH as additive. To distinguish PFASs from
      other chemicals we used the characteristic negative mass defects of PFASs, their
      specific losses of 20 Da (HF) and the presence of series of chromatographic
      peaks, belonging to homologues series with m/z of n*50 Da (CF(2)) or n*100 Da
      (CF(2)CF(2)). The elemental composition of the precursor ions were deducted from
      the accurate m/z values of the deprotonated molecules [M-H](-). In case of in
      source fragmentation, the presence of dimers, e.g. [M(2)-H](-) and adduct ions
      such as [M-H+solvent](-) and [(M-H)(M-H+Na)(n)](-) were used to confirm the
      identity of the precursor ions. In relation to quantification of PFASs, we
      discuss how their surfactancy influence the ESI processes, challenge their
      handling in solution and choices of precursor-to-product ions for MSMS of e.g.,
      structural PFAS isomers. The method has been used to discover PFASs in industrial
      blends and in extracts from food contact materials.

PMID- 21871632
TI  - Retention behaviour of imidazolium ionic liquid cations on 1.7 MUm ethylene
      bridged hybrid silica column using acetonitrile-rich and water-rich mobile
      phases.
AB  - The potential of 1.7 MUm ethylene bridged hybrid silica phase was investigated
      for the separation of twelve imidazolium-based ionic liquid cations. U-shaped
      retention profile was observed for all solutes with an increase in retention at
      both low and high acetonitrile content. Chromatographic behaviour of imidazolium
      cations in both hydrophilic interaction chromatography (HILIC) and per aqueous
      liquid chromatography (PALC) modes was studied by varying key parameters such as
      buffer concentration and pH, acid additive, organic modifier and column
      temperature. Experimental data provided some evidences that under PALC conditions
      cationic solutes are retained predominantly by mixed hydrophobic/ion-exchange
      interactions. In the HILIC mode, both partitioning and ion-exchange interactions
      are responsible for the retention of solutes. Compared to PALC, HILIC provided
      significantly higher efficiencies with less or even no peak tailing, better
      separation selectivity and greater resistance to overload. In PALC mode gradient
      elution was required to achieve adequate retentivity of all solutes but
      selectivity was not sufficient to distinguish between solutes with very similar
      hydrophobicity. In contrast, under HILIC conditions twelve solutes were almost
      completely resolved in less than 4 min by using isocratic elution. Summarizing,
      it could be concluded that ethylene bridged hybrid silica column providing a dual
      retention mechanism offers the possibility of selecting between the two retention
      modes with opposite separation selectivity, just by changing the composition of
      the mobile phase.

PMID- 21871633
TI  - Application of fast ultrasound water-bath assisted enzymatic hydrolysis--high
      performance liquid chromatography-inductively coupled plasma-mass spectrometry
      procedures for arsenic speciation in seafood materials.
AB  - Enzymatic hydrolysis of seafood materials for isolating arsenic species (As(III),
      As(V), DMA and AsB) has been successfully performed by assisting the procedure
      with ultrasound energy (35 kHz) supplied by an ultrasound water-bath. The use of
      pepsin, as a proteolytic enzyme, under optimized operating conditions (pH 3.0,
      temperature 40 degrees C, enzyme to sample ratio of 0.3) led to an efficient
      assistance of the enzymatic process in a short period of time (from 4.0 to 30
      min). The enzymatic extract was then subjected to a clean-up procedure based on
      ENVI-CarbTM solid phase extraction (SPE). An optimized anion exchange high
      performance liquid chromatography (HPLC) coupled to inductively coupled plasma
      mass spectrometry (ICP-MS) permitted the fast separation (less than 15 min) of
      six different arsenic species (arsenite, As(III); arsenate, As(V);
      dimethylarsinic acid, DMA; and arsenobetaine, AsB; as well as monomethylarsonic
      acid, MMA; and arsenocholine, AsC) in a single run. Relative standard deviations
      (n=11) of the over-all procedure were 7% for AsB and DMA, 11% for As(III) and 9%
      for MMA. HPLC-ICP-MS determinations were performed using aqueous calibrations
      covering arsenic concentrations of 0, 5, 10, 25, 100 and 200 MUg L(-1) (expressed
      as arsenic) for As(III), As(V), MMA, DMA and AsC; and 0, 125, 250, 500, 750, 1000
      and 2000 MUg L(-1) (expressed as arsenic) for AsB. Germanium (5 MUg L(-1)) was
      used as an internal standard. Analytical recoveries from the anion exchange
      column varied from 96 to 105% (enzymatic digests spiked with low target
      concentrations), from 97 to 104% (enzymatic digests spiked with intermediate
      target concentrations), and from 98 to 103% (enzymatic digests spiked with high
      target concentrations). The developed method was successfully applied to two
      certified reference materials (CRMs), DORM-2 and BCR 627, which offer certified
      AsB and DMA contents, and also to different seafood samples (mollusks, white fish
      and cold water fish). Good agreement between certified and found AsB
      concentrations was achieved when analyzing both CRMs; and also, between certified
      and found DMA concentrations in BCR 627. In addition, the sum of the different
      arsenic species concentrations found in most of the analyzed samples was
      statistically similar to the assessed total arsenic concentrations after a total
      sample matrix decomposition treatment.

PMID- 21871634
TI  - Characterization and classification of Western Greek olive oils according to
      cultivar and geographical origin based on volatile compounds.
AB  - The aim of the present study was to characterize and classify olive oils from
      Western Greece according to cultivar and geographical origin, based on volatile
      compound composition, by means of Linear Discriminant Analysis. A total of 51
      olive oil samples were collected during the harvesting period 2007-2008 from six
      regions of Western Greece and from six local cultivars. Forty-five of the samples
      were characterized as extra virgin olive oils. The analysis of volatile compounds
      was performed by Headspace Solid Phase Microextraction-Gas Chromatography/Mass
      Spectrometry (HS-SPME-GC/MS). Fifty-three (53) different volatile compounds were
      tentatively identified and semi-quantified. Using selected volatile compound
      composition data (selection was based on the application of ANOVA to total
      volatiles to determine those variables showing substantial differences among
      samples of different geographical origin/cultivar), the olive oil samples were
      satisfactorily classified according to geographical origin (87.2%) and cultivar
      (74%).

PMID- 21871635
TI  - Short-term zinc supplementation with dispersible tablets or zinc sulfate solution
      yields similar positive effects on plasma zinc concentration of young children in
      Burkina Faso: a randomized controlled trial.
AB  - OBJECTIVE: To assess zinc absorption from dispersible tablets by investigating
      the effects of short-term zinc supplementation, provided either as zinc (Zn)
      sulfate dispersible tablets or solution, on changes in plasma Zn concentration in
      young children. STUDY DESIGN: We conducted a randomized, partially-masked,
      placebo-controlled trial in 451 children 6 to 23 months of age in Burkina Faso,
      randomly assigned to receive a dispersible tablet containing 5 mg Zn, a Zn
      solution containing 5 mg Zn/5 mL, or a placebo solution, daily for 3 weeks. The
      main outcome measure was change in plasma zinc concentration after
      supplementation compared with baseline. RESULTS: The mean plus or minus SD change
      in plasma Zn concentration (MUg/dL) was significantly greater in both Zn
      supplemented groups (tablets: 16.9+/-13.1MUg/dL, liquid: 16.6+/-14.2 MUg/dL),
      compared with the placebo group (0.2+/-10.9 MUg/dL; P<.001, ANOVA). In both Zn
      supplemented groups, but not in the placebo group, change in plasma Zn
      concentration was progressively less with increasing age in months (-0.79
      MUg/dL/mo and -1.15 MUg/dL/mo, respectively; P<.001); this effect did not differ
      in the Zn supplemented groups (P=.18). CONCLUSIONS: Short-term supplementation
      results in a large increase in plasma Zn concentration, regardless of whether the
      additional Zn is provided as a dispersible tablet or solution.

PMID- 21871636
TI  - The relationship of current depressive symptoms and past depression with
      cognitive impairment and instrumental activities of daily living in an elderly
      population: the Sydney Memory and Ageing Study.
AB  - Depressive symptoms are common in the elderly and they have been associated with
      cognitive and functional impairment. However, relatively less is known about the
      relationship of a lifetime history of depression to cognitive impairment and
      functional status. The aim of this cross-sectional study was to assess whether
      current depressive symptoms and past depression are associated with cognitive or
      functional impairment in a community-based sample representative of east Sydney,
      Australia. We also examined whether there was an interaction between current and
      past depression in their effects on cognitive performance. Eight hundred non
      demented aged participants received a neuropsychological assessment, a past
      psychiatric history interview and the 15-item Geriatric Depression Scale. The
      Bayer-Activities of Daily Living scale was completed by an informant to determine
      functional ability. Clinically relevant depressive symptoms were present in 6.1%
      of the sample and 16.6% reported a history of depression. Participants with
      current depression had significantly higher levels of psychological distress and
      anxiety, and lower life satisfaction and performed worse on memory and executive
      function compared to participants without current depression. After controlling
      for anxiety the effect on executive function was no longer significant while the
      effect on memory remained significant. A history of depression was associated
      with worse executive function, higher levels of psychological distress and
      anxiety, and lower life satisfaction. After controlling for psychological
      distress the effect of past depression on executive function was no longer
      significant. There were no significant interactions between current and past
      depression in their effects on cognitive performance. There were no differences
      between participants with or without current depression and with or without past
      depression on functional abilities. These results support the view that current
      and past depressive episodes are associated with poorer cognitive performance but
      not with functional abilities.

PMID- 21871637
TI  - Benthic foraminifera distribution in a tourist lagoon in Rio de Janeiro, Brazil:
      a response to anthropogenic impacts.
AB  - Rodrigo de Freitas Lagoon, located in the Rio de Janeiro City, receives several
      types of polluted discharges. The knowledge of the sediment microfauna correlated
      with heavy metal and organic matter concentrations could supply important data
      about the conditions of the lagoon. The benthic foraminiferal assemblage
      presented larger diversity and more abundant samples in the lagoon entrance than
      in the inner area. The Ammonia tepida - Elphidium excavatum foraminiferal
      assemblage is characterized by dwarf, corroded and weak organisms. Agglutinated
      species were found only near the entrance. Low abundance values and sterility of
      five samples in the inner area (north/northeast) can be caused by high levels of
      heavy metals and organic matter. A. tepida shows negative correlation with
      increasing heavy metals values. PAHs and coprostanol high indexes, and the
      absence or low presence of microfauna in samples around the lagoon margin confirm
      illegal flows from gas stations and domestic sewage.

PMID- 21871638
TI  - Environmental response to sewage treatment strategies: Hong Kong's experience in
      long term water quality monitoring.
AB  - In many coastal cities around the world, marine outfalls are used for disposal of
      partially treated wastewater effluent. The combined use of land-based treatment
      and marine discharge can be a cost-effective and environmentally acceptable
      sewage strategy. Before 2001, screened sewage was discharged into Victoria
      Harbour through many small outfalls. After 2001, the Hong Kong Harbour Area
      Treatment Scheme (HATS) was implemented to improve the water quality in Victoria
      Harbour and surrounding waters. Stage I of HATS involved the construction of a 24
      km long deep tunnel sewerage system to collect sewage from the densely populated
      urban areas of Hong Kong to a centralized sewage treatment plant at Stonecutters
      Island. A sewage flow of 1.4 million m3 d(-1) receives Chemically Enhanced
      Primary Treatment (CEPT) followed by discharge via a 1.2 km long outfall 2 km
      west of the harbor. The ecosystem recovery in Victoria Harbour and the
      environmental response to sewage abatement after the implementation of HATS was
      studied using a 21-year data set from long term monthly water quality monitoring.
      Overall, the pollution control scheme has achieved the intended objectives. The
      sewage abatement has resulted in improved water quality in terms of a significant
      reduction in nutrients and an increase in bottom DO levels. Furthermore, due to
      the efficient tidal mixing and flushing, the impact of the HATS discharge on
      water quality in the vicinity of the outfall location is relatively limited.
      However, Chl a concentrations have not been reduced in Victoria Harbour where
      algal growth is limited by hydrodynamic mixing and water clarity rather than
      nutrient concentrations. Phosphorus removal in the summer is suggested to reduce
      the risk of algal blooms in the more weakly-flushed and stratified southern
      waters, while nutrient removal is less important in other seasons due to the
      pronounced role played by hydrodynamic mixing. The need for disinfection of the
      effluent to reduce bacterial (E. coli) concentrations to acceptable levels is
      also confirmed and has recently been implemented.

PMID- 21871639
TI  - Isolation, characterization of Rhodococcus sp. P14 capable of degrading high
      molecular-weight polycyclic aromatic hydrocarbons and aliphatic hydrocarbons.
AB  - Rhodococcus sp. P14 was isolated from crude oil-contaminated sediments. This
      strain was capable of utilizing three to five rings polycyclic aromatic
      hydrocarbons (PAHs) including phenanthrene (Phe), pyrene (Pyr), and
      benzo[a]pyrene (BaP) as a sole carbon and energy source. After cultivated with
      50mg/L of each PAH, strain P14 removed 43% Phe, 34% Pyr and 30% BaP in 30 d. Four
      different hydroxyphenanthrene products derived from Phe by strain P14 (1,2,3,4
      hydroxyphenanthrene) were detected using SPME-GC-MS. Strain P14 also was capable
      of degrading mineral oil with n-alkanes of C17 to C21 carbon chain length.
      Compared with glucose-grown cells, PAHs-grown cells had decreased contents of
      shorter-chain length fatty acids (<= C16:0), increased contents of C18:0, Me
      C19:0 and disappeared odd-number carbon chain fatty acids. The contents of
      unsaturated C19:1, Me-C19:0 increased and C18:0 decreased in mineral oil-grown
      cells. At the same time, the strain P14 tended to float when cultivated in
      mineral oil-supplemented liquid medium. The degradation capability of P14 to
      alkane and PAHs and its floating characteristics will be very helpful for
      future's application in oil-spill bioremediation.

PMID- 21871640
TI  - Association between muscle strength and metabolic syndrome in older Korean men
      and women: the Korean Longitudinal Study on Health and Aging.
AB  - The objective of the study was to investigate the association between metabolic
      syndrome (MS) and muscle strength in community-dwelling older men and women in
      Korea. Korean men and women 65 years and older living in a single, typical South
      Korean city (n = 647) were enrolled in the Korean Longitudinal Study on Health
      and Aging study. The diagnosis of MS was evaluated according to the definition of
      the National Cholesterol Education Program Adult Treatment Panel III. Isokinetic
      muscle strength of the knee extensors, as determined by peak torque per body
      weight (newton meter per kilogram) and hand-grip strength per body weight (newton
      per kilogram), was measured. Participants without MS had greater leg muscle
      strength and grip strength per weight. The effect of MS on muscle strength was
      more prominent in men than in women in our study population. Only men showed a
      significant interaction between MS and age for muscle strength (P = .014), and
      the effect was greater in men aged 65 to 74 years compared with those older than
      75 years (119.2 +/- 31.2 vs 134.5 +/- 24.3 N m/kg). Participants with MS had
      weaker knee extensor strength after controlling the covariates (beta = -90.80, P
      = .003), and the interaction term (age * MS * male sex) was significant (beta =
      1.00, P = .017). Metabolic syndrome is associated with muscle weakness, and this
      relationship is particularly pronounced in men. Age can modify the impact of MS
      on muscle strength. Men aged 65 to 74 years with MS need a thorough assessment of
      muscle strength to prevent disability.

PMID- 21871641
TI  - Salivary cortisol levels are associated with outcomes of weight reduction therapy
      in obese Japanese patients.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis can increase the
      risk of cardiovascular disease (CVD). However, the detailed relationships of HPA
      axis activity with weight reduction and CVD risk factors in obese patients have
      not been examined. This study was designed to elucidate the associations of
      salivary cortisol levels with weight reduction and CVD risk factors in obese
      patients. As a marker of HPA axis activity, we measured the morning salivary
      cortisol levels of 83 obese Japanese outpatients. We also examined metabolic
      parameters, inflammatory markers, and indicators of arterial stiffness, that is,
      the pulse wave velocity and cardio-ankle vascular index. All 83 obese patients
      underwent 3-month weight reduction therapy with lifestyle modification. At the
      baseline, multivariate regression analysis revealed that only logarithmic
      transformation of C-reactive protein (beta = 0.258, P < .05) and cardio-ankle
      vascular index (beta = 0.233, P < .05) were independent determinants of the
      salivary cortisol levels. However, other metabolic parameters were not
      significantly associated with the salivary cortisol levels. In addition, lower
      salivary cortisol levels and higher body weight at the baseline were the only
      independent determinants of successful weight loss through the weight reduction
      therapy (P < .01). The present study demonstrates that the baseline morning
      salivary cortisol levels are significantly associated with the levels of an
      inflammatory marker, arterial stiffness, and successful weight reduction in obese
      patients. Therefore, salivary cortisol could be a useful marker for assessing and
      managing body weight and CVD risk factors in obese patients.

PMID- 21871642
TI  - Association of vitamin D receptor gene polymorphisms with insulin resistance and
      response to vitamin D.
AB  - The objectives of the study were to determine associations between single
      nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene and insulin
      resistance and the effects of these SNPs on changes in insulin sensitivity in
      response to vitamin D supplementation. The research described here was an
      extension of the Surya study. Genotyping of the Cdx-2, FokI, BsmI, ApaI, and TaqI
      SNPs was carried out on 239 South Asian women in New Zealand using polymerase
      chain reaction-based techniques. Associations of these genotypes and 3' end
      haplotypes with insulin resistance were determined using multiple regression
      analysis. Associations between SNP genotypes and responses in insulin sensitivity
      to vitamin D supplementation (4000 IU vitamin D(3) per day) were also determined
      for a subset (81) of these women. BsmI BB, ApaI AA, and TaqI tt genotypes were
      significantly associated with lower insulin resistance compared with BsmI bb,
      ApaI aa, and TaqI TT, respectively, in the cohort of 239 women. Furthermore,
      homozygosity of the haplotypes baT and BAt was associated with higher and lower
      insulin resistance, respectively, compared with no copies of their respective
      alleles. Of the 81 subjects who were supplemented with vitamin D, women with the
      FokI Ff genotype showed a significantly greater improvement in insulin
      sensitivity (increase of 29.4 [2.9, 38.1]) compared with women with the FokI FF
      genotype (increase of 2.3 [-11.5, 10.1]). This study has highlighted the
      association of vitamin D responsiveness and insulin resistance with VDR gene
      polymorphisms. This is the first study to determine associations between all
      three. Genotyping of the VDR gene may provide a predictive measure for insulin
      resistance in response to vitamin D intervention.

PMID- 21871643
TI  - S100A16 mediation of weight gain attenuation induced by dietary calcium.
AB  - Dietary calcium influences the regulation of energy metabolism, and weight gain
      is attenuated by a high-calcium diet. S100A16 is a novel calcium-binding
      signaling protein of the EF-hand superfamily that promotes adipogenesis. This
      study aimed to investigate the effect of S100A16 on weight gain attenuation with
      a calcium-rich diet. An obese rat model was produced after feeding with a high
      fat diet. Animals were randomly divided into 4 groups according to the diet
      provided over 8 weeks: normal diet group; high-fat, normal-calcium diet group;
      high-fat, high-calcium diet (HH) group; and high-fat, low-calcium diet group.
      Serum biochemistry was analyzed, and body weight and visceral fat pads were
      measured. Expression of S100A16 was assayed by Western blotting. Adipogenesis was
      detected by oil red O staining. Increases in body weight and visceral fat weight
      were attenuated in the HH group. High-calcium diets decreased the concentrations
      of serum total cholesterol and triglyceride. Expression of S100A16 decreased in
      the HH group. Using the 3T3-L1 preadipocyte model, it was observed that elevation
      of intracellular Ca(2+) via calcium ionophores led to the exclusion of S100A16
      from the nucleus. Overexpression of S100A16 in 3T3-L1 preadipocytes enhanced
      adipogenesis, although a significant reduction in Akt phosphorylation was also
      detected. High-calcium diets were associated with a significant reduction in body
      weight gain. High-calcium diets may lead to nuclear exclusion of S100A16, which
      results in the inhibition of adipogenesis and enhanced insulin sensitivity.

PMID- 21871644
TI  - Interconverting flavanone glucosides and other phenolic compounds in Lippia
      salviaefolia Cham. ethanol extracts.
AB  - Four interconverting flavanone glycosides [(2R)- and (2S)-3',4',5,6
      tetrahydroxyflavanone 7-O-beta-D-glucopyranoside, and (2R)- and (2S)-3',4',5,8
      tetrahydroxyflavanone 7-O-beta-D-glucopyranoside], in addition to eight known
      flavonoids [naringenin, asebogenin, sakuranetin, 6-hydroxyluteolin 7-O-beta-D
      glucoside, (2R)- and (2S)-eriodictyol 7-O-beta-D-glucopyranoside, aromadendrin
      and phloretin], three phenylpropanoid glycosides [forsythoside B, alyssonoside
      and verbascoside] and the epoxylignan lariciresinol 4'-O-beta-D-glucopyranoside
      were isolated and identified in the EtOH extract of the aerial parts of Lippia
      salviaefolia Cham. The phytochemical study herein was guided by preliminary
      antioxidant tests, namely, beta-carotene protection and 2,2-diphenyl-1
      picrylhydrazyl (DPPH) free radical scavenging activity. The crude extracts, their
      active fractions and the isolated compounds were assayed against intracellular
      reactive oxygen species (ROS) and human embryonic kidney HEK-293 and human
      melanoma M14 cancer cell growth. Aromadendrin and phloretin were able to
      counteract elevation of ROS induced by the oxidant t-butylhydroperoxide (t-BOOH)
      in HEK-293 cells, whereas phloretin strongly protected HEK-293 cells from ROS
      damage at 1 MUM. Additionally, phloretin exhibited a significant growth
      inhibitory effect at 20-40 MUM in both HEK-293 and M14 cells and induced a
      concentration dependent apoptosis at 20 MUM in M14 cells, suggesting a selective
      action towards malignant cells. Due to their equilibria, the four interconverting
      flavanone glycosides were studied using 1D and 2D NMR, HPLC-CD-PDA and HRMS
      analyses.

PMID- 21871645
TI  - [Peripheral facial palsy after cerebral venous thrombosis].

PMID- 21871646
TI  - Current status of schistosomiasis and soil-transmitted helminthiasis in Beyla and
      Macenta Prefectures, Forest Guinea.
AB  - A cross-sectional survey was undertaken in children aged 9-14 years in Beyla and
      Macenta Prefectures, Forest Guinea. Stool samples were examined by Kato-Katz and
      urine samples were examined by the centrifugation method. The overall prevalence
      and intensity of infection was 66.2% and 462.4 eggs per gram of faeces (epg) for
      Schistosoma mansoni, 21.0% and 17.8 eggs per 10ml of urine for S. haematobium,
      51.2% and 507.5 epg for hookworm, 8.1% and 89.1 epg for Ascaris lumbricoides and
      2.4% and 16.7 epg for Trichuris trichiura. The overall prevalence of
      schistosomiasis (S. mansoni and/or S. haematobium) was 70.7%. The prevalence of
      schistosomiasis was similar to those reported in the 1990s in the region;
      however, the prevalence of soil-transmitted helminths has since fallen. These
      findings illustrate the need for schistosomiasis control in Guinea.

PMID- 21871647
TI  - Mechanistic and structural studies of the N-hydroxylating flavoprotein
      monooxygenases.
AB  - The N-hydroxylating flavoprotein monooxygenases are siderophore biosynthetic
      enzymes that catalyze the hydroxylation of the sidechain amino-group of ornithine
      or lysine or the primary amino-group of putrescine. This hydroxylated product is
      subsequently formylated or acylated and incorporated into the siderophore.
      Importantly, the modified amino-group is a hydroxamate and serves as an iron
      chelating moiety in the siderophore. This review describes recent work to
      characterize the ornithine hydroxylases from Pseudomonas aeruginosa (PvdA) and
      Aspergillus fumigatus (SidA) and the lysine hydroxylase from Escherichia coli
      (IucD). This includes summaries of steady and transient state kinetic data for
      all three enzymes and the X-ray crystallographic structure of PvdA.

PMID- 21871648
TI  - An experimental study on using rare earth elements to trace phosphorous losses
      from nonpoint sources.
AB  - Controlling phosphorous (P) inputs through management of its sources and
      transport is critical for limiting freshwater eutrophication. In this study,
      characteristics of exogenous rare earth elements (REEs) and P and their losses
      with surface runoff (both in the water and sediments) during simulated rainfall
      experiments (83 mm h-1) were investigated. The results revealed that on average
      most REEs (La, 94%; Nd, 93%; Sm, 96%) and P (96%) transported with sediments in
      the runoff. The total amounts of losses of REEs and P in the runoff were
      significantly correlated, suggesting the possibility of using REEs to trace the
      fate of agricultural nonpoint P losses.

PMID- 21871649
TI  - Effects of physical activity on the deposition of traffic-related particles into
      the human lungs in silico.
AB  - Traffic-related particle emissions have been a great concern over a number of
      years due to their adverse health effects. In this research project, traffic
      related particle deposition in the human lungs is studied using lung deposition
      estimates based on the ICRP 66 model. This study covers four human groups, i.e.
      adult males, adult females and two groups of children aged 5 and 10 years. The
      study examines particle deposition in the human lungs in relation to four
      different physical exercise levels, i.e. sleeping, sitting, light exercise and
      heavy exercise. To conduct the study, the particle size distributions of diesel
      and compressed natural gas (CNG) busses were monitored in field laboratory
      conditions. The study indicates that the total number of diesel particles
      measured is greater than the total number of CNG particles. The results further
      display that most of the diesel particles measured are smaller than 0.2 MUm,
      whereas the CNG particles are smaller than 0.05 MUm in aerodynamic diameter. The
      level of physical exercise, as well as the age and gender of a person affects the
      deposition of particles in the lungs. An increase in the physical activity
      results in larger amounts of small-size particles penetrating deeper into the
      respiratory system. The lung deposition of particles in males was substantially
      different compared to that of females and children. The deposited dose of
      particles was generally lower for females than for males and further lower for
      children than for females. This article argues that these groups should be
      discussed separately when conducting exposure assessments and that the level of
      physical activity should be taken into account when assessing potential health
      consequences.

PMID- 21871650
TI  - Assessment of fly ash-aided phytostabilisation of highly contaminated soils after
      an 8-year field trial Part 2. Influence on plants.
AB  - Aided phytostabilisation is a cost-efficient technique to manage metal
      contaminated areas, particularly in the presence of extensive pollution. Plant
      establishment and survival in highly metal-contaminated soils are crucial for
      phytostabilisation success, as metal toxicity for plants is widely reported. A
      relevant phytostabilisation solution must limit metal transfer through the food
      chain. Therefore, this study aimed at evaluating the long-term efficiency of
      aided phytostabilisation on former agricultural soils highly contaminated by
      cadmium, lead, and zinc. The influence of afforestation and fly ash amendments on
      reducing metal phytoavailability was investigated as were their effects on plant
      development. Before being planted with a tree mix, the site was divided into
      three plots: a reference plot with no amendment, a plot amended with silico
      aluminous fly ash and one with sulfo-calcic fly ash. Unlike Salix alba and
      Quercus robur, Alnus glutinosa, Acer pseudoplatanus and Robinia pseudoacacia grew
      well on the site and accumulated, overall, quite low concentrations of metals in
      their leaves and young twigs. This suggests that these three species have an
      excluder phenotype for Cd, Zn and Pb. After 8 years, metal availability to A.
      glutinosa, A. pseudoplatanus and R. pseudoacacia, and translocation to their
      above-ground parts, strongly decreased in fly ash-amended soils. Such decreases
      fit well together with the depletion of CaCl(2)-extractable metals in amended
      soils. Although both fly ashes were effective to decrease Cd, Pb and Zn
      concentrations in above-ground parts of trees, the sulfo-calcic ash was more
      efficient.

PMID- 21871651
TI  - Apatite ore mine tailings as an amendment for remediation of a lead-contaminated
      shooting range soil.
AB  - This study investigated the use of tailings from apatite ore beneficiation in the
      remediation of a heavily contaminated shooting range soil. The tailings
      originating in Siilinjarvi carbonatite complex, Finland, consist of apatite
      residues accompanied by phlogopite and calcite. In a pot experiment, organic top
      layer of a boreal forest soil predisposed to pellet-derived lead (Pb) was amended
      with tailings of various particle-sizes (O>0.2mm, O<0.2mm and unsieved material)
      differing in their mineralogical composition. After 9-, 10-, 14- and 21-month
      incubation, the samples were monitored for tailings-induced changes in the
      different Pb pools by means of sequential fractionation. Following the
      incubation, the samples were extracted with water and the extracts were analyzed
      for Pb species distribution by means of a cation exchange resin. The results
      revealed that Pb was continuously released from the shotgun pellet fragments due
      to weathering. However, the apatite and calcite compartments in the tailings
      counteracted the mobility of the released Pb through the formation of sparingly
      soluble fluorpyromorphite and cerussite. Furthermore, the tailings efficiently
      reduced the bioavailability of Pb by transferring it from the water-soluble and
      exchangeable pools into the organic one. The material also increased the
      proportion of the less toxic non-cationic Pb to the total dissolved Pb from the
      initial level of 5% to 9-12%. The results suggest that the tailings-induced
      stabilization of Pb may be an environmentally sound remediation technique at
      polluted sites.

PMID- 21871652
TI  - Target fishes on artificial reefs: evidences of impacts over nearby natural
      environments.
AB  - Topics in artificial reef research have included a wide number of themes but a
      major portion of published works are about the attraction that artificial reefs
      exert over fishes that reside in natural reefs. In the present work, underwater
      visual censuses of fishes were conducted at both artificial and natural reefs,
      aiming at verifying whether fishes are attracted or and produced on artificial
      reefs. Length frequency, mean biomass and frequency of occurrence of four fish
      genera targeted by local fisheries (Caranx, Haemulon, Lutjanus and Mycteroperca)
      were compared between two artificial and two natural reefs. Evidences of both
      production and attraction of target reef fishes by artificial reefs were found.
      Production is evidenced by the enormous abundance of recruits of a single grunt
      species, the tomtate (Haemulon aurolineatum Cuvier). The high concentration of
      adults of predator demersal fishes (Mycteroperca spp. and Lutjanus spp.), present
      at low density on natural reefs, is the main evidence for attraction by
      artificial reefs. Results are inconclusive for the pelagic predators Caranx spp.
      The attraction that artificial reefs exert over large demersal predators can
      negatively affect nearby natural areas through shifts in predation, competition
      or nutrient input. Production can affect benthic communities in soft bottoms
      adjacent to artificial reefs by foraging of reef-associated fishes. Even when
      unplanned for fisheries purposes artificial reefs are often submitted to
      commercial and recreational fisheries and, due to the strong attraction they
      exert over large predators, these structures need harvest regulations.

PMID- 21871653
TI  - Potential chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis in
      rats: myrrh (Commiphora molmol) vs. turmeric (Curcuma longa).
AB  - The aim of the present study was to assess the potential chemopreventive effects
      of myrrh (Commiphora molmol) vs. turmeric (Curcuma longa) in hepatocarcinogenic
      rats induced by a single intraperitoneal injection of diethylnitrosamine (DENA)
      (200 mg/kg body weight). Ninety male Wistar rats used in this study were randomly
      divided into six equal groups (n=15). Group 1 rats served as negative controls;
      group 2 received a single i.p. injection of DENA and served as positive controls.
      Rats in both groups were fed on basal diet. Group 3 rats were fed a diet
      containing 5% turmeric, whereas group 4 rats were fed a diet containing 2% myrrh.
      Rats in groups 5 and 6 received a single i.p. injection of DENA and were fed
      diets containing 5% turmeric and 2% myrrh, respectively. The study demonstrated
      that DENA caused a significant increase in serum indices of liver enzymes and
      also severe histological and immunohistochemical changes in hepatic tissues.
      These included disorganized hepatic parenchyma, appearance of pseudoacinar and
      trabecular arrays of hepatocytes and alterations in CD10-immunoreactivity.
      Dietary supplementation of turmeric relatively improved the biochemical
      parameters to values approximating those of the negative controls and delayed the
      initiation of carcinogenesis. In contrast, myrrh did not improve the biochemical
      parameters or delay the hepatocarcinogenesis. Both turmeric and myrrh induced
      significant biochemical and histological changes in non-treated rats. In
      conclusion, DENA significantly changes the biological enzymatic activities in
      serum and the integrity of hepatic tissues. Phytochemicals with potential
      hepatoprotective effects must be applied cautiously owing to their potential
      hepatotoxicity.

PMID- 21871654
TI  - A multiinstitutional study of the effects of medical therapy for lower urinary
      symptoms on the perioperative outcomes of holmium laser enucleation of the
      prostate.
AB  - OBJECTIVE: The purpose of this research was to examine the influence of 5ARI and
      other benign prostatic hyperplasia medical therapies on the perioperative
      outcomes after holmium laser enucleation of the prostate (HoLEP). During HoLEP,
      the identification of the planes between the transitional and peripheral zones of
      the prostate is paramount to the success of the procedure. It has been proposed
      that delineating the prostate capsule may be more difficult after the use of 5
      alpha reductase inhibitor (5ARI) medications. METHODS: A retrospective review of
      patients who underwent HoLEP was performed. Patients were stratified according to
      their preoperative medication usage. Patient characteristics, pretreatment
      prostate characteristics and symptom scores, perioperative parameters and
      complications, and posttreatment symptoms scores were evaluated. RESULTS: There
      were 176 patients analyzed; 52 (29%) were on no medications, 54 (31%) were on an
      alpha-blocker (AB) alone, 13 (8%) were on a 5ARI alone, and 57 (32%) were on both
      a 5ARI and an AB. Enucleation rate (resected volume/resection time) was
      significantly faster in the combination group. The preoperative prostate-specific
      antigen value was significantly higher in the 5ARI group. A trend in the lower
      hemoglobin change was seen favoring the 5ARI group, but this did not reach
      statistical significance. Evaluating the groups based on the use of 5ARIs either
      alone or in combination vs no 5ARI confirmed that 5ARI was associated with a
      significantly faster enucleation rate. CONCLUSION: Preoperative 5ARI use does not
      appear to adversely alter the outcomes during HoLEP.

PMID- 21871655
TI  - Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1.
AB  - T cell differentiation into distinct functional effector and inhibitory subsets
      is regulated, in part, by the cytokine environment present at the time of antigen
      recognition. Here, we show that hypoxia-inducible factor 1 (HIF-1), a key
      metabolic sensor, regulates the balance between regulatory T cell (T(reg)) and
      T(H)17 differentiation. HIF-1 enhances T(H)17 development through direct
      transcriptional activation of RORgammat and via tertiary complex formation with
      RORgammat and p300 recruitment to the IL-17 promoter, thereby regulating T(H)17
      signature genes. Concurrently, HIF-1 attenuates T(reg) development by binding
      Foxp3 and targeting it for proteasomal degradation. Importantly, this regulation
      occurs under both normoxic and hypoxic conditions. Mice with HIF-1alpha-deficient
      T cells are resistant to induction of T(H)17-dependent experimental autoimmune
      encephalitis associated with diminished T(H)17 and increased T(reg) cells. These
      findings highlight the importance of metabolic cues in T cell fate determination
      and suggest that metabolic modulation could ameliorate certain T cell-based
      immune pathologies.

PMID- 21871656
TI  - A German outbreak of haemolytic uraemic syndrome.

PMID- 21871657
TI  - Management of an acute outbreak of diarrhoea-associated haemolytic uraemic
      syndrome with early plasma exchange in adults from southern Denmark: an
      observational study.
AB  - BACKGROUND: Diarrhoea-associated haemolytic uraemic syndrome in adults is a life
      threatening, but rare multisystem disorder that is characterised by acute
      haemolytic anaemia, thrombocytopenia, and renal insufficiency. We aimed to assess
      the success of management of this disorder with plasma exchange therapy. METHODS:
      Patients diagnosed with diarrhoea-associated haemolytic uraemic syndrome in
      southern Denmark were treated with daily plasma exchange by centrifugation and
      substitution with fresh frozen plasma. Stool culture and serological testing was
      done to identify the cause of disease, and the success of management with plasma
      exchange therapy was assessed from change in platelet count, glomerular
      filtration rate, and lactate dehydrogenase. FINDINGS: During May 25-28, 2011,
      five patients with a median age of 62 years (range 44-70) presented with
      diarrhoea-associated haemolytic uraemic syndrome, which was caused by an unusual
      Shiga-toxin-producing Escherichia coli serotype O104:H4. Strains of E coli showed
      a high resistance to third-generation cephalosporins because the strains had
      extended-spectrum beta lactamases. After plasma exchange, median platelet count
      and glomerular filtration rate increased, median lactate dehydrogenase
      concentration decreased, and neurological status improved. The time interval from
      onset of bloody diarrhoea to start of plasma exchange had an inverse correlation
      with reduction of lactate dehydrogenase concentrations by plasma exchange
      (p=0.02). All patients were discharged with normal neurological status at 7 days
      (range 5-8) after starting plasma exchange. INTERPRETATION: Early plasma exchange
      might ameliorate the course of diarrhoea-associated haemolytic uraemic syndrome
      in adults. However, this finding should be verified in randomised controlled
      trials FUNDING: None.

PMID- 21871658
TI  - Human hepatocytes and endothelial cells in organotypic membrane systems.
AB  - The realization of organotypic liver model that exhibits stable phenotype is a
      major challenge in the field of liver tissue engineering. In this study we
      developed liver organotypic co-culture systems by using synthetic and
      biodegradable membranes with primary human hepatocytes and human umbilical vein
      endothelial cells (HUVEC). Synthetic membranes prepared by a polymeric blend
      constituted of modified polyetheretherketone (PEEK-WC) and polyurethane (PU) and
      biodegradable chitosan membranes were developed by phase inversion technique and
      used in homotypic and organotypic culture systems. The morphological and
      functional characteristics of cells in the organotypic co-culture membrane
      systems were evaluated in comparison with homotypic cultures and traditional
      systems. Hepatocytes in the organotypic co-culture systems exhibit compact
      polyhedral cells with round nuclei and well demarcated cell-cell borders like in
      vivo, as a result of heterotypic interaction with HUVECs. In addition HUVECs
      formed tube-like structures directly through the interactions with the membranes
      and hepatocytes and indirectly through the secretion of ECM proteins which
      secretion improved in the organotypic co-culture membrane systems. The
      heterotypic cell-cell contacts have beneficial effect on the hepatocyte albumin
      production, urea synthesis and drug biotransformation. The developed organotypic
      co-culture membrane systems elicit liver specific functions in vitro and could be
      applied for the realization of engineered liver tissues to be used in tissue
      engineering, drug metabolism studies and bioartificial liver devices.

PMID- 21871659
TI  - Core-shell cell bodies composed of human cbMSCs and HUVECs for functional
      vasculogenesis.
AB  - Rapid induction and creation of functional vascular networks is essential for the
      success of treating ischemic tissues. The formation of mature and functional
      vascular networks requires the cooperation of endothelial cells (ECs) and
      perivascular cells. In the study, we used a thermo-responsive hydrogel system to
      fabricate core-shell cell bodies composed of cord-blood mesenchymal stem cells
      (cbMSCs) and human umbilical vascular ECs (HUVECs) for functional vasculogenesis.
      When seeded on Matrigel, the shelled HUVECs attempted to interact and communicate
      vigorously with the cored cbMSCs initially. Subsequently, HUVECs migrated out and
      formed tubular structures; cbMSCs were observed to coalesce around the HUVEC
      derived tubes. With time progressing, the tubular networks continued to expand
      without regression, indicating that cbMSCs might function as perivascular cells
      to stabilize the nascent networks. In the in vivo study, cbMSC/HUVEC bodies were
      embedded in Matrigel and implanted subcutaneously in nude mice. At day 7, visible
      blood-filled vessels were clearly identified within the implant containing
      cbMSC/HUVEC bodies, indicating that the formed vessels anastomosed with the host
      vasculature. The cored cbMSCs were stained positive for smooth muscle actin,
      suggesting that they underwent smooth muscle differentiation and formed
      microvessels with the shelled HUVECs, as the role of perivascular cells. These
      data confirm that the formation of mature vessels requires heterotypic
      cooperation of HUVECs and MSCs. This study provides a new strategy for
      therapeutic vasculogenesis, by showing the feasibility of using cbMSC/HUVEC
      bodies to create functional vascular networks.

PMID- 21871660
TI  - The effects of covalently immobilized hyaluronic acid substrates on the adhesion,
      expansion, and differentiation of embryonic stem cells for in vitro tissue
      engineering.
AB  - We investigated the in vitro effects of the molecular weight (MW) of hyaluronic
      acid (HA) on the maintenance of the pluripotency and proliferation of murine
      embryonic stem (ES) cells. High (1000 kDa) or low (4-8 kDa) MW HA was derivatized
      using an ultraviolet-reactive compound, 4-azidoaniline, and the derivative was
      immobilized onto cell culture cover slips. Murine ES cells were cultured on these
      HA surfaces for 5 days. High-MW HA interacted with murine ES cells via CD44,
      whereas low-MW HA interacted with these cells mostly via CD168. ES cells grown on
      both high- and low-MW HA appeared undifferentiated after 3 days. However, more
      cells adhered, proliferated, and exhibited greater amounts of phospho-p42/44
      mitogen-activated-protein-kinase on low- compared with high-MW HA. Expression of
      Oct-3/4 and phosphorylation of STAT3 were enhanced by ES cells on low-MW HA, not
      on high-MW HA. After release from HA, cells cultured on low-MW HA in the presence
      of differentiating medium showed enhanced expression of alpha-SMA or CD31
      compared with cells cultured on high-MW HA. It was concluded that low-MW HA
      substrates were effective in maintaining murine ES cells in a viable and
      undifferentiated state, which favors their use in the propagation of ES cells for
      tissue engineering.

PMID- 21871661
TI  - Bone response to fast-degrading, injectable calcium phosphate cements containing
      PLGA microparticles.
AB  - Apatitic calcium phosphate cements (CPC) are frequently used to fill bone defects
      due to their favourable clinical handling and excellent bone response, but their
      lack of degradability inhibits complete bone regeneration. In order to render
      these injectable CaP cements biodegradable, hollow microspheres made of poly (D,L
      lactic-co-glycolic) acid (PLGA) have been previously used as porogen since these
      microspheres were shown to be able to induce macroporosity upon degradation as
      well as to accelerate CPC degradation by release of acid degradation products.
      Recently, the capacity of PLGA microspheres to form porosity in situ in
      injectable CPCs was optimized by investigating the influence of PLGA
      characteristics such as microsphere morphology (dense vs. hollow) and end-group
      functionalization (acid terminated vs. end-capped) on acid production and
      corresponding porosity formation in vitro. The current study has investigated the
      in vivo bone response to CPCs containing two types of microspheres (hollow and
      dense) made of PLGA with two different end-group functionalizations (end capped
      and acid terminated). Microspheres were embedded in CPC and injected in the
      distal femoral condyle of New Zealand White Rabbits for 6 and 12 weeks.
      Histological results confirmed the excellent biocompatibility and
      osteoconductivity of all tested materials. Composites containing acid terminated
      PLGA microspheres displayed considerable porosity and concomitant bone ingrowth
      after 6 weeks, whereas end capped microspheres only revealed open porosity after
      12 weeks of implantation. In addition, it was found that dense PLGA microspheres
      induced significantly more CPC degradation and bone tissue formation compared to
      hollow PLGA microspheres. In conclusion, it was shown that PLGA microspheres have
      a strong capacity to induce fast degradation of injectable CPC and concomitant
      replacement by bone tissue by controlled release of acid polymeric degradation
      products without compromising the excellent biocompatibility and
      osteoconductivity of the CPC matrix.

PMID- 21871662
TI  - Increased numbers of orexin/hypocretin neurons in a genetic rat depression model.
AB  - The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression
      that displays characteristics similar to those of depressed patients including
      lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic
      neuropeptides such as orexin/hypocretin, melanin-concentrating hormone (MCH) and
      cocaine and amphetamine regulated transcript (CART), that are involved in the
      regulation of both energy metabolism and sleep, have recently been implicated
      also in depression. We therefore hypothesized that alterations in these
      neuropeptide systems may play a role in the development of the FSL phenotype with
      both depressive like behavior, metabolic abnormalities and sleep disturbances. In
      this study, we first confirmed that the FSL rats displayed increased immobility
      in the Porsolt forced swim test compared to their control strain, the Flinders
      Resistant Line (FRL), which is indicative of depressive-like behavior. We then
      examined the number of orexin-, MCH- and CART-immunopositive neurons in the
      hypothalamus using stereological analyses. We found that the total number of
      orexin-positive neurons was higher in the hypothalamus of female FSL rats
      compared to female FRL rats, whereas no changes in the MCH or CART populations
      could be detected between the strains. Chronic treatment with the selective
      serotonin reuptake inhibitor (SSRI) escitalopram reduced immobility only in the
      FRL rats where it also increased the number of MCH positive neurons compared to
      untreated rats. These findings support the view that orexin may be involved in
      depression and strengthen the notion that the "depressed" brain responds
      differently to pharmacological interventions than the normal brain.

PMID- 21871663
TI  - Parents' self-reporting of child physical maltreatment in Yuncheng City, China.
AB  - OBJECTIVE: To investigate the prevalence of child physical maltreatment (CPM) by
      parents in a city locating in central-western region of China and identify
      associated risk factors. METHODS: Cross-sectional survey was carried out among a
      randomly sampled population of primary school students' parents in Yuncheng City.
      Data on parental CPM during the past 3 months, definition of CPM, Parenting
      Scale, parent-child interaction attitudes, social support, socio-demographic
      background were collected by a self-report questionnaire. Logistic regression
      analyses were used to investigate the associations between CPM and related risk
      factors. RESULTS: Of parents from 1,394 primary school students, there were 595
      (42.7%) and 301 (21.6%) of them reported that they had minor/severe CPM behaviors
      toward their children during the past 3 months, respectively. The risk factors
      that were significantly associated with both prevalence and frequencies of
      minor/severe CPM included child problem behaviors, overreactivity and hostility
      parenting. CONCLUSION: CPM by parents is not uncommon in China. More attention
      should be paid to programs that help parents learn parenting skills and use
      nonviolent child discipline.

PMID- 21871664
TI  - Early life developmental effects of marine persistent organic pollutants on the
      sea urchin Psammechinus miliaris.
AB  - A new 16-day echinoid early life stage (ELS) bioassay was developed to allow for
      prolonged observation of possible adverse effects during embryogenesis and larval
      development of the sea urchin Psammechinus miliaris. Subsequently, the newly
      developed bioassay was applied to study the effects of key marine persistent
      organic pollutants (POPs). Mortality, morphological abnormalities and larval
      development stages were quantified at specific time points during the 16-day
      experimental period. In contrast to amphibians and fish, P. miliaris early life
      development was not sensitive to dioxin-like toxicity in the prolonged early life
      stage test. Triclosan (TCS) levels higher than 500 nM were acutely toxic during
      embryo development. Morphological abnormalities were induced at concentrations
      higher than 50 nM hexabromocyclododecane (HBCD) and 1000 nM tetrabromobisphenol A
      (TBBPA). Larval development was delayed above 25 nM HBCD and 500 nM TBBPA.
      Heptadecafluorooctane sulfonic acid (PFOS) exposure slightly accelerated larval
      development at 9 days post-fertilization (dpf). However, the accelerated
      development was no longer observed at the end of the test period (16 dpf). The
      newly developed 16-day echinoid ELS bioassay proved to be sensitive to toxic
      effects of POPs that can be monitored for individual echinoid larvae. The most
      sensitive and dose related endpoint was the number of developmental penalty
      points. By manipulation of the housing conditions, the reproductive season could
      be extended from 3 to 9 months per year and the ELS experiments could be
      performed in artificial sea water as well.

PMID- 21871665
TI  - Assessing, mapping and validating site-specific ecotoxicological risk for
      pesticide mixtures: a case study for small scale hot spots in aquatic and
      terrestrial environments.
AB  - Mixture toxicity is a real world problem and as such requires risk assessment
      solutions that can be applied within different geographic regions, across
      different spatial scales and in situations where the quantity of data available
      for the assessment varies. Moreover, the need for site specific procedures for
      assessing ecotoxicological risk for non-target species in non-target ecosystems
      also has to be recognised. The work presented in the paper addresses the real
      world effects of pesticide mixtures on natural communities. Initially, the
      location of risk hotspots is theoretically estimated through exposure modelling
      and the use of available toxicity data to predict potential community effects.
      The concept of Concentration Addition (CA) is applied to describe responses
      resulting from exposure of multiple pesticides The developed and refined exposure
      models are georeferenced (GIS-based) and include environmental and physico
      chemical parameters, and site specific information on pesticide usage and land
      use. As a test of the risk assessment framework, the procedures have been applied
      on a suitable study areas, notably the River Meolo basin (Northern Italy), a
      catchment characterised by intensive agriculture, as well as comparative area for
      some assessments. Within the studied areas, the risks for individual chemicals
      and complex mixtures have been assessed on aquatic and terrestrial aboveground
      and belowground communities. Results from ecological surveys have been used to
      validate these risk assessment model predictions. Value and limitation of the
      approaches are described and the possibilities for larger scale applications in
      risk assessment are also discussed.

PMID- 21871666
TI  - Role of aquaporin 3 in development, subtypes and activation of dendritic cells.
AB  - Dendritic cells (DCs) uptake soluble antigens and large volumes of fluid through
      macropinocytosis and migrate for antigen presentation. Aquaporin 3 (AQP3), a
      water and glycerol transporting protein, is highly expressed in immature DCs. To
      elucidate the role of AQP3 in DC function, we investigated subtype and activation
      of DCs in AQP3 knock-out (AQP3(-/-)) mice. Depletion of AQP3 did not affect the
      development of bone marrow-derived DCs (BM-DCs) by GM-CSF or the Flt3 ligand and
      the level of expression of CD86 on unstimulated and LPS-stimulated BM-DCs. In
      addition, the percentage of CD86(+) cells among splenic cDCs after LPS treatment
      in both in vitro and in vivo conditions was similar in wild type and AQP3(-/-)
      mice. However, the frequency of CD4(+) cDCs in the spleen of AQP3(-/-) mice was
      significantly lower than that of wild type mice. There was higher expression of
      CD103 in the CD8(+) subpopulation of splenic cDCs from AQP3(-/-) mice than wild
      type mice. In the dermis, more CD103-expressing cells were detected in AQP3(-/-)
      mice than in wild type mice and the LPS-induced decrease of CD103(+) dermal DCs
      was impaired in AQP3(-/-) mice. AQP3 depletion did not affect the uptake of
      either albumin or dextran by CD11c(+) splenic DCs. However, HgCl(2), which is an
      AQP inhibitor, significantly inhibited the uptake of albumin but not dextran by
      CD11c(+) splenic DCs. These results suggest that AQP3 may play a role in
      modulating DC population and migration.

PMID- 21871667
TI  - Use of auxiliary psychiatric treatment during a 5-year follow-up among patients
      receiving short- or long-term psychotherapy.
AB  - BACKGROUND: The need for treatment is, despite of its obvious usefulness, a
      scarcely used measure of effectiveness in psychotherapy trials. This study
      considers changes in the need for auxiliary psychiatric treatment after starting
      short- and long-term psychotherapy and psychoanalysis. METHODS: Altogether 326
      psychiatric outpatients with mood or anxiety disorder were randomly assigned to
      solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP), or
      long-term psychodynamic psychotherapy (LPP) while 41 self-selected patients were
      allocated to psychoanalysis (PA). The patients were followed for 5 years from
      start of treatment. Outcome measures were use of auxiliary psychotherapy,
      psychotropic medication, and hospitalization for mental reasons. RESULTS: About
      60% of the patients used auxiliary treatment during the follow-up. It was most
      common in the short-term therapy groups and its incidence was highest during the
      first year after the start of therapy. The average numbers of all therapy
      sessions among patients starting the therapy were 60, 70, 240, and 670 in SFT,
      SPP, LPP, and PA, respectively, whereas the corresponding average numbers of
      study therapy sessions alone were 10, 19, 232, and 646. Over 50% of the patients
      receiving short-term therapy received on average 4-6 times more therapy sessions
      than initially assigned. LIMITATIONS: Post-randomization withdrawal was uneven.
      CONCLUSIONS: Auxiliary treatment is usual among patients receiving short- and
      long-term therapies, and apparently becomes common shortly after the start of
      treatment. Auxiliary treatment can be used as an outcome measure indicating the
      need for treatment, should be monitored clinically and considered when
      interpreting the results of effectiveness studies.

PMID- 21871668
TI  - A pilot study to identify pre- and peri-operative risk factors for airway
      complications following adenotonsillectomy for treatment of severe pediatric OSA.
AB  - OBJECTIVE: A pilot study to identify risk factors predicting post-operative
      complications in children with severe OSA undergoing adenotonsillectomy. METHODS:
      Retrospective review in a tertiary care academic institution. Two-stage least
      squares regression analysis and instrumental variable analysis to allow for
      modeling of pre- and peri-operative risk factors as having significance in
      predicting post-operative morbidity. RESULTS: Eighty-three children (mean age
      4.88 +/- 3.09 years) with apnea-hypopnea index (AHI) >= 10 who were observed
      overnight following adenotonsillectomy were evaluated for rates of major
      (increased level of care, CPAP/BiPAP use, pulmonary edema and reintubation) and
      minor (oxygen saturation <90%) airway complications as well as total observation
      costs. Major and minor complications occurred in 4.8% and 19.3% of children,
      respectively. Age <2 years (p<0.01), AHI >24 (p<0.05), intra-operative
      laryngospasm requiring treatment (p<0.05), oxygen saturations <90% on room air in
      PACU (p<0.05) and PACU stay >100 min (p<0.01) independently predicted post
      operative complications. Children with any one of these factors experienced a 38%
      complication rate versus 4% in all others. CONCLUSIONS: This pilot study
      identified pre- and peri-operative risk factors that collectively can be
      investigated as predictors of post-operative airway complications in a
      prospective study. By identifying preliminary results comparing the complication
      rates between those children with and without these risk factors, we will be able
      to calculate the sample size for a future prospective validation study. Such a
      study is necessary to understand the safety and potential significant cost
      savings of observing children without risk factors on the pediatric floor and not
      in an ICU setting. A best practice algorithm can be created for children with
      severe OSA only after completing this prospective study.

PMID- 21871669
TI  - Receiver-operated characteristics (ROCs) of the relationships between obesity
      indices and multiple risk factors (MRFs) for atherosclerosis at different ages in
      men and women.
AB  - The aim of this study was to clarify whether age affects ROC curves for the
      relationships between obesity indices and MRFs for atherosclerosis. Subjects were
      35-70-year-old men (n=37,697) and women (n=19,891) who received health checkup
      examinations. ROC curves were analyzed for relationships of body mass index
      (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) with MRFs for
      atherosclerosis consisting of two or more risk factors (RFs) of metabolic
      syndrome (MetS) including high blood pressure, dyslipidemia (hypertriglyceridemia
      and/or hypo-HDL-cholesterolemia) and hyperglycemia. Both in men and women, AUC
      (area under the curve) of the ROC curves tended to be smaller as age increased.
      In women, cut-off values of WHtR tended to be higher as age increased, while no
      apparent relationships were found between age and cut-off values of BMI and WC in
      women and between age and cut-off values of the three obesity indices in men. The
      results suggest that both in men and women, the associations between obesity and
      MRFs for atherosclerosis become weaker as age increases, while age does not
      influence cut-off values of obesity indices except for higher WHtR at an older
      age in women.

PMID- 21871670
TI  - Analysis of cellular senescence induced by lipopolysaccharide in pulmonary
      alveolar epithelial cells.
AB  - In this work, it was examined the possibility of lipopolysaccharide (LPS) causing
      cellular senescence in lung alveolar epithelial cells. Then, it was clarified how
      this cellular senescence phenomenon is associated with oxidative stress effect
      induced by LPS and whether antioxidants could inhibit reduced cellular viability
      by oxidant stress effect of LPS. In cell viability using cell counting kit-8,
      exposure to LPS decreased cellular viability and induced growth arrest in a
      concentration-dependent manner. The pre-apoptotic concentration of LPS was
      determined by caspase activation using a Caspase-Glo 3/7 luminescence assay kit.
      This concentration of LPS caused morphologic characteristics shown in senescent
      cells and elevated senescence-associated beta-galactosidase activity. In
      addition, lysosomal content associated with senescence was increased by LPS at
      the pre-apoptotic concentration. However, this concentration of LPS did not
      shorten the telomere length. Exposure to LPS resulted in the formation of
      hydrogen peroxide in a concentration-dependent manner. The ability of LPS to
      reduce cellular viability was inhibited by the presence of glutathione. This
      study revealed that LPS could induce cellular senescence in lung alveloar
      epithelial cells, and these phenomena were closely associated with hydrogen
      peroxide production by LPS. Taken together, it is suggested that LPS-induced
      cellular senescence may play an important role in limiting the tissue repair
      response after sepsis.

PMID- 21871671
TI  - Association between sex hormone levels and leukoaraiosis (LA) in older Korean
      men.
AB  - LA, altered white matter signal intensities seen on MR brain scans, has been
      shown to be associated with cerebrovascular risk factors and microangiopathy.
      Although the cerebrovascular system is also a target for sex hormones, little is
      known about the association between the two. In this study, we investigated the
      association between male sex hormone levels and LA in old men by examining free
      testosterone index (FTI), total testosterone, sex hormone-binding globulin
      (SHBG), and LA in 342 Korean men (aged 50-80 years). The odds ratios (ORs) for LA
      were calculated using multivariate logistic regression. The ORs (95% CIs) for LA
      were 1.06 (1.01-1.10) for FTI, 1.01 (0.93-1.10) for total testosterone, and 0.97
      (0.94-1.01) for SHBG after adjusting for age, smoking status, alcohol intake,
      regular exercise, BMI, mean arterial blood pressure, resting heart rate, white
      blood cell counts, fasting plasma glucose, total cholesterol, triglyceride, HDL
      cholesterol, hypertension medications, diabetes medications, and hyperlipidemia
      medications. The results of this study indicate that high FTI is independently
      associated with greater prevalence of LA in older men. Accordingly, a higher FTI
      may be an additional surrogate marker in assessing LA.

PMID- 21871672
TI  - The risk for nursing home admission (NHA) did not change in ten years--a
      prospective cohort study with five-year follow-up.
AB  - In an aging population the burden on health care systems depends on the
      proportion of lifetime spent in good or poor health. The objective of this study
      was to examine the effect of a ten-year cohort difference on NHA, indicating
      changes in lifetime spent without severe disabilities. Additionally, important
      risk factors for NHA were identified. The data were obtained from two cohort
      studies of elderly people. Cohort A (1991-1993) comprised 74+ patients from 20
      German general practices and cohort B (2002-2003) 70+ patients from 14 general
      practices. The merged sample consisted of 2301 community dwelling patients that
      contacted their general practitioner within a 12-month period during the
      respective enquiry period. After an initial assessment at study entry,
      participants were monitored over a five-year period respective NHA and death. The
      Cox proportional hazards model was used including socio-epidemic data, state of
      health, chronic diseases, dementia, health system usage, and social support. The
      ten-year cohort-difference was no predictor of NHA within a 5-year period.
      Significant influencing variables were: age (OR 1.10), living with others (OR
      0.59), no auxiliary person (OR 1.69), mild forgetfulness (OR 2.12), clear
      cognitive impairment (OR 3.74), severe cognitive disturbance (3.61), loss of
      memory (11.83), walking difficulties (OR 1.53), impaired vision (OR 1.90), and
      cancer (OR 0.22). This study could not find a cohort effect on NHA. With regard
      to increased life expectancy the findings do not support the compression of
      morbidity hypothesis. The identified influencing variables contribute to the
      understanding of NHA risk factors.

PMID- 21871673
TI  - Cortical bone resorption rate in elderly persons: estimates from long-term in
      vivo measurements of (90)Sr in the skeleton.
AB  - The rate of cortical bone resorption was assessed from long-term in vivo
      measurements of (90)Sr content in the skeleton for men aged 50-80 years and for
      women 0-30 years after menopause. Measurements of (90)Sr were conducted with a
      whole body counter (WBC) for residents of the Techa Riverside communities
      (Southern Urals, Russia), who ingested large amounts of (90)Sr as a result of
      releases of liquid radioactive wastes into the river from the Mayak plutonium
      facility in early 1950s. The results of this study showed an increase in the rate
      of cortical bone resorption in both men and women, as based on the use of
      accidentally ingested (90)Sr as a tracer for bone metabolism. In men there was a
      continuous gradual increase in the rate of cortical bone resorption after 55
      years from 2.8 to 4.5%/year by the age of 75 years. In women, there was a doubled
      increase in the rate of cortical bone resorption after menopause of up to
      6%/year; then the rate remained unchanged for 10-12 years with a subsequent
      gradual decline down to 5-5.5%/year. Comparison of the rate of cortical bone
      resorption in men and women older than 55 years showed that women expressed
      significantly higher levels of cortical bone resorption.

PMID- 21871674
TI  - Mobility assessment of hip fracture patients during a post-acute rehabilitation
      program.
AB  - Our aim was to describe improvement in mobility level in hip fracture patients
      during a post-acute rehabilitation program and examine variables that may impede
      mobility improvement. A retrospective chart review of 138 patients with a
      proximal hip fracture, admitted consecutively during 2006 was conducted. Main
      outcome measurements were: 6-meter-walking-time (6mWT), rate of improvement (RI)
      in the 6mWT, gait velocity (GV), functional independence measure (FIM), motor FIM
      (mFIM) and length of stay (LOS). Most patients (118, 85.5%) showed improvement in
      the 6mWT (mean 16.05 +/- 20.2s, median 12.08). At discharge, 117 patients (84.7%)
      achieved GV within household ambulation (<0.4m/s). Patients with high initial GV
      needed shorter rehabilitation time compare to patients with low admission GV
      (27.5 +/- 12.1 days vs. 31.7 +/- 12.2 days; p=0.042). The high RI group (>=
      1s/day) achieved significantly higher admission and discharge FIM scores (70.7 +/
      15.9 vs. 64.1 +/- 16.9, p=0.023; 87.3 +/- 15.8 vs. 79.9 +/- 17.4, p=0.013,
      respectively) and higher admission and discharge mFIM scores (45.3 +/- 12.9 vs.
      40.8.1 +/- 12.7, p=0.049; 60.7 +/- 12.4 vs. 56.2 +/- 13.4, p=0.045, respectively)
      compared with the low performance group (<1s/day). Logistic regression analyzed
      the variables with significant predictive value for achieving high RI (>=
      1s/day): performance of the 6mWT at FIM >= 4 (OR 1.092; 95% CI, 1.056-1.129) and
      admission FIM score (OR 1.054; 95% CI, 1.023-1.085). Post-acute hip fracture
      patients capable of bearing weight on their injured leg, with minimal assistance
      [manual assistance of <= 25% (FIM >= 4)] may considerably improve their mobility
      regardless of their disability, cognitive level or neurological history. Most
      patients achieved GV enabling them to ambulate short distances within the home.

PMID- 21871675
TI  - Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures (SOF)
      criteria and adverse health outcomes among community-dwelling older outpatients
      in Italy. A one-year prospective cohort study.
AB  - The easy-to-apply SOF criteria for frailty were recently validated in studies
      conducted in the U.S. only. In order to determine the ability of the SOF criteria
      to predict adverse health outcomes at a one-year follow-up in a sample of older
      outpatients in Italy we carried out a prospective cohort study on 265 community
      dwelling outpatients aged 65+ (mean age 81.5 years) consecutively referred to a
      geriatric clinic. At baseline participants underwent a comprehensive geriatric
      assessment (CGA) including evaluation of their frailty status according to the
      SOF criteria. At a one-year follow-up, between June and December 2010, we
      investigated nursing home placement and death in all participants as well as any
      fall, any admission to the emergency department (ED), any hospitalization and a
      greater disability among the subset of subjects still living at home. One year
      after the visit 231 subjects were still living at home (87.2%), 9 had been placed
      in a nursing home (3.4%) and 25 had died (9.4%). Frailty was associated with a
      greater risk of falls (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.05
      3.83, p=0.035), hospitalization (OR 2.08, 95% CI 1.02-4.24, p=0.045) and death
      (OR 3.07, 95% 1.02-4.24, p=0.045) after correction for demographic
      characteristics, comorbidity including dementia and depression, socioeconomic
      position and severe disability. Thus, in an older outpatient population in Italy
      the frailty syndrome diagnosed according to the SOF criteria was an independent
      predictor of several adverse health outcomes.

PMID- 21871676
TI  - "It's a hair-dryer...No, it's a drill": misidentification-related false
      recognitions in younger and older adults.
AB  - Memory for visual objects, although typically highly accurate, can be distorted,
      especially in older adults. Here we asked whether also erroneous identifications
      of visual objects subsequently corrected and replaced by a correct identification
      might induce false recognitions, and whether this is more likely to occur in
      older people. For this aim a new paradigm was developed. In the first phase,
      participants performed a visual object identification task with degraded pictures
      of objects and produced correct and false but subsequently corrected
      identifications. In the second phase, participants performed a surprise
      recognition task in which also false identifications were presented. False
      identifications elicited false recognitions, with a stronger and more reliable
      effect in elderly participants, suggesting that correcting the initial visual
      error is not sufficient to correct the memory for the experience. Moreover,
      misidentification-related false recognitions coexisted in memory along with
      correct recognitions of correct identifications. These findings are discussed in
      relation with age-related deficits in memory updating and strategic retrieval.

PMID- 21871677
TI  - Impact of rheumatic diseases and chronic joint symptoms on quality of life in the
      elderly.
AB  - Musculoskeletal disorders are the major causes of the pain in the elderly
      population. Rheumatic conditions restrict participation in activities and
      mobility, as well as cause difficulties in the execution of self-care tasks. The
      assessment of health related quality of life (HRQOL) is an important indicator of
      the impact of rheumatic diseases on the physical, mental and social aspects. This
      study aims to analyze the influence of rheumatic diseases and chronic joint
      symptoms on the quality of life of the elderly (n=2209) aged 60 years or over.
      The effects of rheumatism and joint symptoms on quality of life were investigated
      by the Outcome Study Short-Form Health Survey (SF-36), and this analysis was
      adjusted for age and sex. The univariate analysis of variance and analysis of
      covariance (ANOVA and ANCOVAS) were used for statistical procedures, p<=0.05.
      Rheumatic diseases affected: functional capacity (F(1, 2012))=10.9 and pain (F(1,
      2012))=34.77. Joint symptoms affected all components of the SF-36: physical
      functioning (F(1, 2012))=10.9; physical problems (F(1, 2012))=72.61; pain (F(1,
      2012))=164.29; general health (F(1, 2012))=71.95; vitality (F(1, 2012))=55.78;
      social aspect (F(1, 2012))=73.14; emotional aspect (F(1, 2012))=49.09 and mental
      health (F(1, 2012))=44.72. There was a significant impact of rheumatic diseases
      on physical health, and that joint symptoms affected self-evaluations of physical
      and mental health. These results will contribute to a better understanding of
      this systemic disease and will be used for planning effective interventions.

PMID- 21871678
TI  - Admission Norton scale scores (ANSS) and postoperative complications following
      hip fracture surgery in the elderly.
AB  - We sought to determine if low ANSS, usually associated with high pressure ulcer
      risk, are also associated with postoperative complications and in-hospital
      mortality following hip fracture surgery in the elderly. This was a retrospective
      cross-sectional study conducted in a tertiary medical center. The medical charts
      of consecutive elderly (>= 65 years) patients admitted for hip fracture surgery
      were studied for the following measurements: ANSS, demographic data, co
      morbidities, postoperative complications, the need for revision procedures, and
      in-hospital mortality. Except for pressure ulcers, postoperative complications
      included: acute coronary syndrome, acute renal failure, confusion, pneumonia,
      urinary tract infection, venous thromboembolism, and wound infection. The final
      cohort included 269 patients: 198 (73.6%) females and 71 (26.4%) males. Mean age
      for the entire cohort was 82.8 +/- 0.4 years. Most patients underwent an internal
      fixation (n=146; 54.3%) or hemiarthroplasty (n=92; 34.2%). Overall, 110 (40.9%)
      patients had low (<15) ANSS. Patients with low ANSS had significantly more
      postoperative complications relative to patients with high ANSS (0.77 +/- 0.09
      vs. 0.23 +/- 0.04; p<0.0001). Among all postoperative complications, urinary
      tract infection was independently associated with low ANSS (p<0.0001). ANSS were
      independently associated with postoperative complications (p<0.0001), the need
      for revision procedures (p=0.019), and in-hospital mortality (p=0.016). We
      conclude that the Norton scoring system may be used for predicting postoperative
      complications and in-hospital mortality following hip fracture surgery in the
      elderly.

PMID- 21871679
TI  - Biomimetic nanopores: learning from and about nature.
AB  - Through recent advances in nanotechnology and molecular engineering, biomimetics 
      the development of synthetic systems that imitate biological structures and
      processes - is now emerging at the nanoscale. In this review, we explore
      biomimetic nanopores and nanochannels. Biological systems are full of nano-scale
      channels and pores that inspire us to devise artificial pores that demonstrate
      molecular selectivity or other functional advantages. Moreover, with a biomimetic
      approach, we can also study biological pores, through bottom-up engineering
      approaches whereby constituent components can be investigated outside the complex
      cellular environment.

PMID- 21871680
TI  - Fruit improvement using intragenesis and artificial microRNA.
AB  - Genetic engineering methods based on the use of transgenes have been successfully
      adopted to improve crops. A novel all-native DNA gene technology consists of the
      creation of intragenic constructs by isolating genetic elements from a crop,
      rearranging them in vitro, and inserting them back into the plant. The ever
      increasing genomic information and the elucidation of the molecular mechanisms
      that control fruit development could be exploited to confer the desired fruit
      phenotypes using endogenous DNA. The spatial/temporal regulation of genes can be
      modified by using appropriate endogenous regulatory elements, such as fruit
      specific promoters. In addition, intragenic silencing can be employed to
      downregulate fruit-related genes. Here, we describe the available tools for
      intragenic manipulation of early phases of fleshy fruit initiation.

PMID- 21871681
TI  - Force direction pattern stabilizes sagittal plane mechanics of human walking.
AB  - The neural control and mechanics of human bipedalism are inadequately understood.
      The variable at the interface of neural control and body mechanics that is key to
      upright posture during human walking is the force of the ground on the foot
      (ground reaction force, F). We present a model that predicts sagittal plane F
      direction as passing through a divergent point (DP) fixed in a reference frame
      attached to the person. Four reference frames were tested to identify which
      provided the simplest and most accurate description of F direction. For all
      reference frames, the DP model predicted nearly all the observed variation in F
      direction and whole body angular momentum during single leg stance. The reference
      frame with vertical orientation and with origin on the pelvis provided the best
      combination of accuracy and simplicity. The DP was located higher than the CM and
      the predicted F produced a pattern of torque about the CM that caused body pitch
      oscillations that disrupted upright posture. Despite those oscillations, that
      torque was evidence of a stability mechanism that may be a critical component
      enabling humans to remain upright while walking and performing other tasks.

PMID- 21871682
TI  - Driving skills of young adults with developmental coordination disorder:
      Maintaining control and avoiding hazards.
AB  - In this study we assess for the first time the driving skills of young adults
      with developmental coordination disorder (DCD). We use a virtual city and a
      driving simulator to examine steering control, speed regulation and the responses
      to pedestrians on the road. Participants were adolescents and young adults who
      had been diagnosed with the disorder as children. For most participants the
      symptoms were maintained (DCD group) but for others they had largely dissipated
      (AD group). We also invited typically developing (control) participants matched
      in age, gender, and driving experience to the DCD and AD participants. Compared
      to their matched controls, the DCD group showed difficulties in steering when
      turning bends but not when driving along straight roads. Although the average
      speed of the DCD group was similar to their controls this may have been too fast
      for them to steer effectively around the bends. The DCD group also took 50% more
      time to react to pedestrians who walked towards their path. We found no such
      differences between the AD and their matched controls. We discuss the results in
      terms of visual information processing and suggest further applied and
      fundamental research on this topic.

PMID- 21871683
TI  - Quantification of Tri5 gene, expression, and deoxynivalenol production during the
      malting of barley.
AB  - Fusarium can survive, grow, and produce mycotoxins during malting. We evaluated
      the percentage of barley kernels infected with Fusarium (FI) and deoxynivalenol
      (DON) concentration in three barley treatments (high-quality, naturally infected,
      and Fusarium graminearum inoculated barley) during various stages of malting. We
      also applied real-time polymerase chain reaction (real-time PCR) and real-time
      reverse transcriptase PCR (real-time RT-PCR) methods to quantify trichothecene
      producing (Tri5) DNA concentration and expression, respectively. We observed that
      FI significantly (P<0.05) increased during the germination stage of malting in
      all barley treatments. Temperatures of 49 degrees C and higher during kilning
      reduced the FI in high-quality barley treatments, but for inoculated treatments
      temperatures in excess of 60 degrees C were needed to reduce FI. The Tri5 DNA
      concentration ranged from non-detectable to 3.9 ng/50mg, 0.1 to 109.8 ng/50mg and
      3.4 to 397.5 ng/50 mg in malted high-quality, inoculated and naturally infected
      barley treatments respectively. Strong gene expression (Tri5) in naturally
      infected barley treatments was found during the third day of germination, when
      compared to high-quality and inoculated barley treatments during malting.
      Deoxynivalenol was present even at high kilning temperatures, as DON is heat
      stable. The average DON concentration ranged from non-detectable to 0.1 MUg/g,
      non-detectable to 1.1 MUg/g, and 1.5 to 45.9 MUg/g during various stages of
      malting in high-quality, inoculated and infected barley and malt samples
      respectively. Overall, the last 2 days of germination and initial stages of
      kilning were peak stages for FI, Tri5 gene production, Tri5 gene expression and
      DON production.

PMID- 21871684
TI  - Mother and daughter carrying the same KCNJ11 mutation but with a different
      response to switching from insulin to sulfonylurea.
AB  - KCNJ11 gene mutations are related to permanent neonatal diabetes mellitus (PNDM).
      Glycemic stability minimizes the risk of complications. Sulfonylureas (SU) are
      the proven best therapeutic option. We report a 18-month follow-up of switching
      from insulin to SU in a mother and her daughter with PNDM due to KCNJ11 mutation.

PMID- 21871685
TI  - Changes in serum adiponectin concentrations and endothelial function after
      intensive insulin treatment in people with newly diagnosed type 2 diabetes: a
      pilot study.
AB  - AIMS: We aimed to assess changes in serum adiponectin and endothelial function
      after intensive insulin treatment in patients with newly diagnosed type 2
      diabetes mellitus (T2DM). METHODS: Patients with newly diagnosed T2DM were
      randomly assigned to Group A (intensive insulin treatment) or Group B
      (conventional insulin treatment). Before treatment and 2 weeks after plasma
      glucose concentrations had been maintained at the specified concentrations, blood
      samples were obtained to measure serum adiponectin and nitric oxide (NO)
      concentrations. A total of 21 patients were randomized to each Group. RESULTS:
      Adiponectin, NO, endothelium-dependent vasodilation (EDD), and endothelium
      independent vasodilation (EID) measures were significantly higher post-treatment
      than pre-treatment in Group A (all P < 0.05). Only EID was significantly higher
      in Group B (P<0.05). Post-treatment adiponectin and NO concentrations, and EDD
      were significantly higher in Group A compared with Group B (all P<0.05). Both
      treatment regimens were well tolerated (all patients completed the study). The
      most common adverse event was hypoglycemia. Thus, early intensive insulin therapy
      can increase serum adiponectin and NO concentrations and improve endothelial
      function in patients with newly diagnosed T2DM. CONCLUSIONS: These effects may
      underlie the reduced incidence of microvascular and macrovascular in patients who
      receive early intensive hypoglycemic therapy.

PMID- 21871686
TI  - Efficacy and safety of saxagliptin added to metformin in Asian people with type 2
      diabetes mellitus: a randomized controlled trial.
AB  - AIM: To assess efficacy and safety of saxagliptin added to metformin versus
      placebo plus metformin in Asian patients with type 2 diabetes mellitus (T2DM) and
      inadequate glycemic control on metformin alone. METHODS: Adults (HbA(1c) 7.0
      10.0%, on stable metformin >= 1500 mg/day) were randomized 1:1 to saxagliptin 5mg
      daily plus metformin (n = 283) or placebo plus metformin (n = 287). The primary
      end point was HbA(1c) change from baseline to Week 24. RESULTS: Saxagliptin plus
      metformin provided significant adjusted mean decreases versus placebo plus
      metformin (p <= 0.0052) in HbA(1c) (-0.78% versus -0.37%), fasting plasma glucose
      (-1.14 mmol/L versus -0.58 mmol/L), and postprandial glucose area under the curve
      from 0 to 180 min (-315 mmol min/L versus -160 mmol min/L). Significantly more
      saxagliptin-treated patients achieved a therapeutic glycemic response
      (HbA(1c)<7.0%) (46.5% versus 30.5%; p = 0.0001). The proportion of patients
      experiencing adverse events (excluding hypoglycemia) was similar for saxagliptin
      plus metformin (42.8%) versus placebo plus metformin (40.8%). Hypoglycemic events
      were reported in 1.4% of patients in each group. CONCLUSION: Saxagliptin added to
      metformin significantly improved glycemic control and was well tolerated in Asian
      patients with T2DM who had inadequate glycemic control with metformin and diet
      and lifestyle modification.

PMID- 21871687
TI  - A systematic review and comparison of HIV contact tracing laws in Canada.
AB  - OBJECTIVES: Public health officials and health providers need to be aware of the
      legislation documenting contact tracing in their jurisdiction to advise HIV
      positive clients of their rights, and to systematically perform their duties. The
      objective is to outline and compare the contact tracing laws in 13 jurisdictions
      in Canada, and to provide policy recommendations. METHODS: A systematic review
      was performed to outline and compare the laws in Canadian jurisdictions regarding
      HIV contact tracing. Specific manual searches were done in websites of Canadian
      provincial and territorial departments of health. RESULTS: For thirteen provinces
      and territories within Canada eleven laws were found. No laws directly pertaining
      to partner notification or contact tracing were found in Newfoundland and
      Labrador or Quebec. CONCLUSIONS: Public health officials should ensure that
      contact tracing practices and policies accurately reflect the current regulations
      without compromising their patients' confidentiality. It is recommended that each
      province/territory would benefit from standardized contact tracing regulations
      which are imbedded in communicable disease legislation. Regulations with
      provisions for informed consent, confidentiality, multiple counselling sessions,
      clear procedures in duty to warn cases, and domestic violence screening would be
      considered best practice.

PMID- 21871688
TI  - A review of atlas-based segmentation for magnetic resonance brain images.
AB  - Normal and abnormal brains can be segmented by registering the target image with
      an atlas. Here, an atlas is defined as the combination of an intensity image
      (template) and its segmented image (the atlas labels). After registering the
      atlas template and the target image, the atlas labels are propagated to the
      target image. We define this process as atlas-based segmentation. In recent
      years, researchers have investigated registration algorithms to match atlases to
      query subjects and also strategies for atlas construction. In this paper we
      present a review of the automated approaches for atlas-based segmentation of
      magnetic resonance brain images. We aim to point out the strengths and weaknesses
      of atlas-based methods and suggest new research directions. We use two different
      criteria to present the methods. First, we refer to the algorithms according to
      their atlas-based strategy: label propagation, multi-atlas methods, and
      probabilistic techniques. Subsequently, we classify the methods according to
      their medical target: the brain and its internal structures, tissue segmentation
      in healthy subjects, tissue segmentation in fetus, neonates and elderly subjects,
      and segmentation of damaged brains. A quantitative comparison of the results
      reported in the literature is also presented.

PMID- 21871689
TI  - Cosolvent flushing for the remediation of PAHs from former manufactured gas
      plants.
AB  - Cosolvent flushing is a technique that has been proposed for the removal of
      hydrophobic organic contaminants in the subsurface. Cosolvents have been shown to
      dramatically increase the solubility of such compounds compared to the aqueous
      solubility; however, limited data are available on the effectiveness of
      cosolvents for field-contaminated media. In this work, we examine cosolvent
      flushing for the removal of polycyclic aromatic hydrocarbons (PAHs) in soil from
      a former manufactured gas plant (FMGP). Batch studies confirmed that the
      relationship between the soil-cosolvent partitioning coefficient (K(i)) and the
      volume fraction of cosolvent (f(c)) followed a standard log-linear equation.
      Using methanol at an fc of 0.95, column studies were conducted at varying length
      scales, ranging from 11.9 to 110 cm. Removal of PAH compounds was determined as a
      function of pore volumes (PVs) of cosolvent flushed. Despite using a high f(c),
      rate and chromatographic effects were observed in all the columns. PAH effluent
      concentrations were modeled using a common two-site sorption model. Model fits
      were improved by using MeOH breakthrough curves to determine fitted dispersion
      coefficients. Fitted mass-transfer rates were two to three orders of magnitude
      lower than predicted values based on published data using artificially
      contaminated sands.

PMID- 21871690
TI  - Tuberculous retropharyngeal abscess as a cause of oropharyngeal dysphagia.
AB  - Tuberculosis is known to affect almost every organ in the body, but its
      manifestations in the head and neck region are quite rare. A tuberculous
      retropharyngeal abscess is a very rare condition and can be the cause of
      oropharyngeal dysphagia. It is usually secondary to tuberculosis of the spine and
      has the potential of significant morbidity and mortality if not treated
      appropriately. We present a case of a 74-year-old man with a retropharyngeal
      abscess with no evidence of spinal tuberculosis.

PMID- 21871691
TI  - [Reliability of the VIDA questionnaire for assessing instrumental activities of
      daily living (iADL) in the elderly].
AB  - OBJECTIVE: To analyse the inter- and intra-examiner reliability of the VIDA
      questionnaire, and their concordance with the "timed get up and go" test in
      people aged >=75 years. DESIGN: Descriptive study of a diagnostic test. LOCATION:
      Primary Health Care. SUBJECTS-INTERVENTION: Application of 71 pairs of VIDA
      questionnaire, by one (38) or two professionals (33), in people aged >=75 years
      with no significant sensory or physical-psychic impairment. Stratified sample
      based on ADL (Barthel index) to obtain a variety of responses that would ensure a
      range of scores of the questionnaire. MAIN MEASUREMENTS: Overall score of VIDA
      questionnaire, "get up and go" test (functional), Pfeiffer questionnaire
      (cognitive), and risk factors of frailty (comorbidity, falls, recent
      hospitalisation, sensory disturbance, social impairment, polypharmacy). RESULTS:
      Mean age 81.3 years+/-4.8, with a 65.5% moderate-severe change in Barthel index.
      The mean score of the questionnaire was 31.3+/-7.9, with a rank of 11 to 38
      (maximum). There were no differences according to gender (P=0.78). Inter-examiner
      reliability (n 33): Intraclass Correlation Coefficient (ICC) 0.94, 95% Confidence
      Interval (CI) 0.88-0.97, P<0.0001. Intra-examiner reliability (n 38): ICC 0.96,
      CI 0.93-0.98, P<0.0001. Correlation coefficient (rho of Spearman) with the "get
      up and go" test (n 67) 0.61 (moderate), P<0.0001. Lower score if there are >= 2
      frailty factors (P=0.015). CONCLUSIONS: VIDA questionnaire is a very reliable
      tool, with no gender bias. It demonstrates an association with other
      functionality measures and with frailty factors in the elderly.

PMID- 21871692
TI  - [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human
      primates and its pathophysiological implications (II)].
AB  - INTRODUCTION: In the ageing process there are some species of non-human primates
      which can show some of the defining characteristics of the Alzheimer's disease
      (AD) of man, both in neuropathological changes and cognitive-behavioural
      symptoms. The study of these species is of prime importance to understand AD and
      develop therapies to combat this neurodegenerative disease. DEVELOPMENT: In this
      second part of the study, these AD features are discussed in the most important
      non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet 
      Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and
      M. arctoides) and experimental models (lesional, neurotoxic, pharmacological,
      immunological, etc.) non-human primates. In all these models cerebral amyloid
      neuropathology can occur in senility, although with different levels of incidence
      (100% in vervets;<30% in macaques). The differences between normal and
      pathological (Alzheimer's) senility in these species are difficult to establish
      due to the lack of cognitive-behavioural studies in the many groups analysed, as
      well as the controversy in the results of these studies when they were carried
      out. However, in some macaques, a correlation between a high degree of functional
      brain impairment and a large number of neuropathological changes ("possible AD")
      has been found. CONCLUSIONS: In some non-human primates, such as the macaque, the
      existence of a possible continuum between "normal" ageing process, "normal"
      ageing with no deep neuropathological and cognitive-behavioural changes, and
      "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other
      cases, such as the Caribbean vervet, neuropathological changes are constant and
      quite marked, but its impact on cognition and behaviour does not seem to be very
      important. This does assume the possible existence in the human senile
      physiological regression of a stable phase without dementia even if
      neuropathological changes appeared.

PMID- 21871693
TI  - [Validation of the Spanish version of the short forms of the Urogenital Distress
      Inventory (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7) in pregnant
      women].
AB  - OBJECTIVE: To validate two measurement instruments, the UDI-6 and the IIQ-7, for
      the study of urinary incontinence and its impact on the quality of life of
      pregnant women. METHODS: We carried out a validation study of a diagnostic tool.
      A total of 181 pregnant women completed the UDI-6 and IIQ-7 questionnaires.
      Feasibility, internal consistency, reliability, and construct and criteria
      validity were analyzed. RESULTS: Self-administration of the short forms of the
      UDI-6 and IIQ-7 questionnaires took less than 5minutes and the maximum rate of no
      answer per item was 3.3%. Cronbach's alpha was 0.667 for the UDI-6 and was 0.910
      for the IIQ-7. The reliability of the UDI-6 in the diagnosis of urinary
      incontinence showed Kappa statistic values of between 0.856 and 0.966, and the
      intra-class correlation coefficients of the UDI-6 and IIQ-7 were 0.902 and 0.954,
      respectively. Average values of the UDI-6 and IIQ-7 were higher in women with
      mixed incontinence, were lower in women with stress incontinence and increased
      with daily losses (p<0.01). The correlation between the UDI-6 and the
      International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF)
      (CCI=0.497; 95% CI: 0.326-0.625) and between the IIQ-7 and ICIQ-SF (CCI=0.472;
      95% CI: 0.268-0.619) was moderate. The sensitivity and specificity of the UDI-6
      for the diagnosis of urinary incontinence was 98.9% and 86.5%, respectively.
      CONCLUSIONS: The Spanish versions of the IIQ-7 and UDI-6 are feasible, reliable,
      consistent and valid in the measurement of symptoms and quality of life in
      pregnant Spanish women with urinary incontinence.

PMID- 21871694
TI  - Hybrids of oxoisoaporphine-tacrine congeners: novel acetylcholinesterase and
      acetylcholinesterase-induced beta-amyloid aggregation inhibitors.
AB  - A series of dual binding site acetylcholinesterase (AChE) inhibitors have been
      designed, synthesized, and tested for their ability to inhibit AChE,
      butyrylcholinesterase (BChE), AChE-induced and self-induced beta-amyloid (Abeta)
      aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tacrine
      or its congener, connected through an oligomethylene linker containing an amine
      group at variable position. These hybrids exhibit high AChE inhibitory activity
      with IC(50) values in the nanomolar range in most cases. Moreover, five out of
      the 12 hybrids of this series, particularly those bearing a tetrahydroacridine
      moiety, exhibit a significant in vitro inhibitory activity toward the AChE
      induced and self-induced Abeta aggregation, which makes them promising anti
      Alzheimer drug candidates.

PMID- 21871696
TI  - Physical activity and mental well-being in student nurses.
AB  - There is strong evidence that suggests physical activity can enhance mental well
      being. However, this relationship has not been widely investigated in student
      nurses. A cross-sectional study was conducted to examine the relationship between
      physical activity and mental well-being in undergraduate student nurses (n=215).
      Physical activity was measured using the International Physical Activity
      Questionnaire. Other outcomes included self-esteem, anxiety, depression, life
      satisfaction, outcome expectations and self-efficacy. Almost, a quarter (23.8%)
      of the total sample, were meeting the Department of Health's physical activity
      guideline. Mean body mass index (BMI) was 25.0 with 40% being in the overweight
      to morbidly obese category. Self-esteem was significantly positively correlated
      with total physical activity (r=0.16, p=0.038) and moderate intensity activity
      (r=0.17, p=0.021). No other significant relationships were found between anxiety,
      depression and satisfaction with life and physical activity. Outcome expectations
      for exercise and self-efficacy were significantly positively correlated with
      moderate (r=0.17, p=0.019) and vigorous (r=0.28, p=0.000) intensity activity and
      total physical activity (r=0.29, p=0.000). BMI was significantly positively
      correlated with age (r=0.242, p=0.001), significantly negatively correlated with
      self-efficacy for exercise (r=0.257, p=0.000) and satisfaction with life (r=
      0.144, p=0.041). Regression analysis showed that low self efficacy for exercise
      and increasing age were significant predictors of BMI with a small effect size
      r(2)=0.126, adjusted r(2)=0.112. BMI and physical activity variables collectively
      explained only 2% of the variance for anxiety, 4% for depression, 5% for self
      esteem and 6% for satisfaction with life. BMI was a significant predictor of
      satisfaction with life (Beta=-0.171, p=0.027). Participation in physical activity
      may be influential in improving mental well-being in student nurses. Promoting
      physical activity in student nurses has the potential to increase self-esteem and
      life satisfaction and decrease the risk of anxiety and depression. Further
      research is needed to establish whether this relationship is causal and exists in
      other student nurse populations.

PMID- 21871695
TI  - Synthesis and biological activity of pyrido[3',2':4,5]furo[3,2-d]pyrimidine
      derivatives as novel and potent phosphodiesterase type 4 inhibitors.
AB  - A series of pyrido[3',2':4,5]furo[3,2-d]pyrimidines (PFP) were synthesized and
      tested for phosphodiesterase type 4 (PDE4) inhibitory activity, with the
      potential to treat asthma and chronic obstructive pulmonary disease (COPD).
      Structure-activity relationships within this series, leading to an increase of
      potency on the enzyme, is presented. Both gem-dimethylcyclohexyl moieties fused
      to the pyridine ring and the substitution at the 5 position of the PFP scaffold,
      proved to be key elements in order to get a high affinity in the enzyme.

PMID- 21871697
TI  - Data driven modelling of vertical atmospheric radiation.
AB  - In the Czech Hydrometeorological Institute (CHMI) there exists a unique set of
      meteorological measurements consisting of the values of vertical atmospheric
      levels of beta and gamma radiation. In this paper a stochastic data-driven model
      based on nonlinear regression and on nonhomogeneous Poisson process is suggested.
      In the first part of the paper, growth curves were used to establish an
      appropriate nonlinear regression model. For comparison we considered a
      nonhomogeneous Poisson process with its intensity based on growth curves. In the
      second part both approaches were applied to the real data and compared.
      Computational aspects are briefly discussed as well. The primary goal of this
      paper is to present an improved understanding of the distribution of
      environmental radiation as obtained from the measurements of the vertical
      radioactivity profiles by the radioactivity sonde system.

PMID- 21871698
TI  - End-to-side anastomosis to the external jugular vein: preservation of external
      jugular vein blood flow.

PMID- 21871699
TI  - Contamination and source differentiation of Pb in park soils along an urban-rural
      gradient in Shanghai.
AB  - Urban soil Pb contamination is a great human health risk. Lead distribution and
      source in topsoils from 14 parks in Shanghai, China were investigated along an
      urban-rural gradient. Topsoils were contaminated averagely with 65 mg Pb kg(-1),
      2.5 times higher than local soil background concentrations. HCl-extracts
      contained more anthropogenic Pb signatures than total sample digests as revealed
      by the higher (207/206)Pb and (208/206)Pb ratios in extracts (0.8613 +/- 0.0094
      and 2.1085 +/- 0.0121 versus total digests 0.8575 +/- 0.0098 and 2.0959 +/-
      0.0116). This suggests a higher sensitivity of HCl-extraction than total
      digestion in identifying anthropogenic Pb sources. Coal combustion emission was
      identified as the major anthropogenic Pb source (averagely 47%) while leaded
      gasoline emission contributed 12% overall. Urbanization effects were observed by
      total Pb content and anthropogenic Pb contribution. This study suggests that to
      reduce Pb contamination, Shanghai might have to change its energy composition to
      clean energy.

PMID- 21871700
TI  - On-site and off-site atmospheric PBDEs in an electronic dismantling workshop in
      south China: gas-particle partitioning and human exposure assessment.
AB  - Gas samples and total suspended particle during work and off work time were
      investigated on-site and off-site electronic waste dismantling workshop (I- and O
      EWDW), then compared with plastic recycling workshop (PRW) and waste incineration
      plant (WIP). TSP concentrations and total PBDE were 0.36-2.21 mg/m(3) and 27-2975
      ng/m(3) at different workshops, respectively. BDE-47, -99, and -209 were major
      ?PBDE congeners at I-EWDW and WIP, while BDE-209 was only dominant congener in
      PRW and control sites during work time and all sites during off work time. The
      gas-particle partitioning result was well correlated with the subcooled liquid
      vapor pressure for all samples, except for WIP and I-EDWD, at park during work
      time, and residential area during off work time. The predicted urban curve fitted
      well with measured phi values at O-DEWD during work time, whereas it was slightly
      overestimated or underestimated for others. Exposure assessment revealed the
      highest exposure site was I-EDWD.

PMID- 21871701
TI  - Polychlorinated naphthalenes (PCNs) in riverine and marine sediments of the
      Laizhou Bay area, North China.
AB  - PCN congeners were analyzed in marine and riverine sediments of the Laizhou Bay
      area, North China. Concentrations of PCNs ranged from 0.12 to 5.1 ng g(-)(1) dry
      weight (dw) with a mean value of 1.1 ng g(-)(1) dw. The levels of PCNs varied
      largely, with industrial group approximately ten folds higher than those of the
      rural in riverine sediment. A strong impact by direct discharge from local
      factories was suggested. Similar compositional profiles were found within groups.
      High resemblance of compositional profiles between industrial samples and Halowax
      1014 was observed. It was indicated that PCNs in riverine sediments were mainly
      from release of industrial usage, with additional contributions from industrial
      thermal process at certain sites. In marine sediments, it was suggested that PCNs
      along the coast of Laizhou Bay were mainly controlled by riverine input. While in
      the central bay, PCN distributions were possibly impacted by combined multiple
      factors.

PMID- 21871702
TI  - Techno-politics of genomic nationalism: tracing genomics and its use in drug
      regulation in Japan and Taiwan.
AB  - This paper compares the development of genomics as a form of state project in
      Japan and Taiwan. Broadening the concepts of genomic sovereignty and
      bionationalism, I argue that the establishment and use of genomic databases vary
      according to techno-political context. While both Japan and Taiwan hold
      population-based databases to be necessary for scientific advance and
      competitiveness, they differ in how they have attempted to transform the
      information produced by databases into regulatory schemes for drug approval. The
      effectiveness of Taiwan's biobank is severely limited by the IRB reviewing
      process. By contrast, while updating its regulations for drug approval, Japan, is
      using pharmacogenomics to deal with matters relating to ethnic identity. By
      analysing genomic initiatives in the political context that nurtures them, this
      paper seeks to capture how global science and local societies interact and offers
      insight into the assessment of state-sponsored science in East Asia as they
      become transnational.

PMID- 21871703
TI  - Iron and aluminium based adsorption strategies for removing arsenic from water.
AB  - Arsenic is a commonly occurring toxic metal in natural systems and is the root
      cause of many diseases and disorders. Occurrence of arsenic contaminated water is
      reported from several countries all over the world. A great deal of research over
      recent decades has been motivated by the requirement to lower the concentration
      of arsenic in drinking water and the need to develop low cost techniques which
      can be widely applied for arsenic removal from contaminated water. This review
      briefly presents iron and aluminium based adsorbents for arsenic removal. Studies
      carried out on oxidation of arsenic(III) to arsenic(V) employing various
      oxidising agents to facilitate arsenic removal are briefly mentioned. Effects of
      competing ions, As:Fe ratios, arsenic(V) vs. arsenic(III) removal using
      ferrihydrite as the adsorbent have been discussed. Recent efforts made for
      investigating arsenic adsorption on iron hydroxides/oxyhydroxides/oxides such as
      granular ferric hydroxide, goethite, akaganeite, magnetite and haematite have
      been reviewed. The adsorption behaviours of activated alumina, gibbsite, bauxite,
      activated bauxite, layered double hydroxides are discussed. Point-of-use
      adsorptive remediation methods indicate that Sono Arsenic filter and KanchanTM
      Arsenic filter are in operation at various locations of Bangladesh and Nepal. The
      relative merits and demerits of such filters have been discussed. Evaluation of
      kits used for at-site arsenic estimation by various researchers also forms a part
      of this review.

PMID- 21871704
TI  - Comparison of scanning acoustic microscopy and histology images in characterizing
      surface irregularities among engineered human oral mucosal tissues.
AB  - Acoustic microscopy was used to monitor an ex vivo produced oral mucosal
      equivalent (EVPOME) developed on acellular cadaveric dermis (AlloDerm(r)). As
      seeded cells adhered and grew, they filled in and smoothed out the surface
      irregularities, followed by the production of a keratinized protective outermost
      layer. If noninvasive in vitro ultrasonic monitoring of these cellular changes
      could be developed, then tissue cultivation could be adjusted in-process to
      account for biologic variations in the development of these stratified cell
      layers. Cultured keratinocytes (from freshly obtained oral mucosa) were harvested
      and seeded onto AlloDerm(r) coated with human type IV collagen and cultured 11
      days. EVPOMEs were imaged on the 11th day post-seeding using a scanning acoustic
      microscope (SAM) that consists of a single-element transducer: 61 MHz center
      frequency, 32 MHz bandwidth, 1.52 f-number. The specimen surface was determined
      by thresholding the magnitude of the signal at the first axial incidence of a
      value safely above noise: 20-40 dB above the signal for the water and 2
      dimensional (2-D) ultrasonic images were created using confocal image
      reconstruction. A known area from each micrograph was divided into 12-40 even
      segments and examined for surface irregularities. These irregularities were
      quantified and one-way analysis of variance (ANOVA) and linear regression
      analysis were performed to correlate the surface profiles for both the
      AlloDerm(r) and EVPOME specimens imaged by SAM. Histology micrographs of the
      AlloDerm(r) and EVPOME specimens were also prepared and examined for surface
      irregularities. Unseeded AlloDerm(r) averaged seven to nine surface changes per
      400 MUm. The number of changes in surface irregularities decreased to two to
      three per 400 MUm on the mature EVPOMEs. The numbers of surface irregularities
      between the unseeded AlloDerm(r) vs. developing EVPOME are similar for both
      histology and SAM 2-D B-scan images. For the EVPOME 2-D B-scan micrographs
      produced by SAM, the decrease in surface irregularities is indicative of the
      stratified epithelium formed by seeded oral keratinocytes; verified in the
      histology images between the AlloDerm(r) and EVPOME. A near 1:1 linear
      correlation shows the similarities between the two imaging modalities. SAM
      demonstrates its ability to discern the cell development and differentiation
      occurring on the EVPOME devices. Unlike histology, SAM measurements are
      noninvasive and can be used to monitor tissue graft development without damaging
      any cells/tissues.

PMID- 21871705
TI  - Laparoendoscopic single-site upper urinary tract surgery: assessment of
      postoperative complications and analysis of risk factors.
AB  - BACKGROUND: Laparoendoscopic single-site surgery (LESS) has been developed in an
      attempt to minimise the morbidity and scarring associated with surgical
      intervention. OBJECTIVE: To evaluate the incidence of and the risk factors for
      complications in patients undergoing LESS upper urinary tract surgery. DESIGN,
      SETTING, AND PARTICIPANTS: Between September 2007 and February 2011, 192
      consecutive patients underwent LESS for upper urinary tract diseases at four
      institutions. MEASUREMENTS: All complications occurring at any time after surgery
      were captured, including the inpatient stay as well as in the outpatient setting.
      They were classified as early (onset<30 d), intermediate (onset 31-90 d), or late
      (onset>90 d) complications, depending on the date of onset. All complications
      were graded according to the modified Clavien classification. RESULTS AND
      LIMITATIONS: The patient population was generally young (mean: 55+/-18 yr of
      age), nonobese (mean body mass index [BMI]: 26.5+/-4.8 kg/m2), and healthy (mean
      preoperative American Society of Anaesthesiologists [ASA] score: 2+/-1). Forty
      six patients had had prior abdominal surgery. Mean operative time was 164+/-63
      min, with a mean estimated blood loss (EBL) of 147+/-221 ml. In 77 cases (40%),
      the surgeons required additional ports, with a standard laparoscopy conversion
      rate of 6%. Mean hospital stay was 3.3+/-2.3 d, and the mean visual analogue
      scale (VAS) score at discharge was 1.7+/-1.43. Thirty-three complications were
      recorded-30 early, 2 intermediate, and 1 late-for an overall complication rate of
      17%. Statistically significant associations were noted between the occurrence of
      a complication and age, ASA score, EBL, length of stay (LOS), and malignant
      disease at pathology. Univariable and the multivariable analyses showed that a
      higher ASA score (incidence rate ratio [IRR]: 1.4; 95% confidence interval [CI],
      1.0-2.1; p=0.034) and malignant disease at pathology (IRR: 2.5; 95% CI, 1.3-4.7;
      p=0.039) represented risk factors for complications. Poisson regression analysis
      over time showed a 23% non-statistically significant reduction in risk of
      complications every year (IRR: 0.77; 95% CI, 0.5-1.19; p=0.242). CONCLUSIONS:
      Malignant disease at pathology and high ASA score represent a predictive factor
      for complication after LESS for upper urinary tract surgery. Thus, surgeons
      approaching LESS should start with benign diseases in low-surgical-risk patients
      to minimise the likelihood of postoperative complications.

PMID- 21871706
TI  - Efficacy and safety of tadalafil once daily in the treatment of men with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an
      international randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Tadalafil is being investigated for the treatment of lower urinary
      tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH-LUTS).
      OBJECTIVE: To assess efficacy, including onset, and safety of tadalafil on BPH
      LUTS and the subject's and clinician's perception of changes in urinary symptoms.
      DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo
      controlled, 12-week trial enrolled men >=45 yr of age with BPH-LUTS for >6 mo,
      International Prostate Symptom Score (IPSS) >=13, and maximum urine flow rate
      (Q(max)) >=4 to <=15 ml/s. INTERVENTION: Tadalafil 5mg (n=161) or placebo
      (n=164), once daily. MEASUREMENTS: Analysis of covariance (ANCOVA) modeling
      evaluated change from baseline in continuous efficacy variables. Categoric
      efficacy variables were analyzed with the Cochran-Mantel-Haenszel test, and
      between-group differences in treatment-emergent adverse events (TEAEs) were
      assessed using the Fisher exact test. RESULTS AND LIMITATION: Tadalafil
      significantly improved IPSS results, from baseline to endpoint, compared to
      placebo (-5.6 vs -3.6; p=0.004). Reduction in IPSS results was apparent after 1
      wk and significant after 4 wk (tadalafil -5.3 vs placebo -3.5; p=0.003). The BPH
      Impact Index (BII) was not assessed at week 1; however, BII improvement was
      apparent at 4 wk (tadalafil -1.8 vs placebo -1.2; p=0.029) and continued at 12 wk
      (tadalafil -1.8 vs placebo -1.3; p=0.057). Tadalafil significantly improved the
      International Index of Erectile Function-Erectile Function score in sexually
      active men with erectile dysfunction (ED; 6.7 vs 2.0; p<0.001) at 12 wk (not
      assessed at week 1). Few subjects reported one TEAE or more (p=0.44). For
      tadalafil, the most common TEAEs were headache (3.7%) and back pain (3.1%).
      Tadalafil did not significantly improve Q(max) or reduce postvoid residual
      volume. CONCLUSIONS: Tadalafil 5mg once daily for 12 wk resulted in a clinically
      meaningful reduction in total IPSS results as early as 1 wk and achieved
      statistical significance at 4 wk in men with BPH-LUTS. The adverse event profile
      was consistent with that previously reported in men with ED. TRIAL REGISTRATION:
      This clinical trial is registered on the clinicaltrials.gov website
      (http://www.clinicaltrials.gov). The registration number is NCT00827242.

PMID- 21871707
TI  - Circulating tumour cells as surrogate biomarkers in castration-resistant prostate
      cancer trials.

PMID- 21871708
TI  - Trends in hypospadias surgery: results of a worldwide survey.
AB  - BACKGROUND: Hypospadias is a challenging field of urogenital reconstructive
      surgery, with different techniques currently being used. OBJECTIVE: Evaluate
      international trends in hypospadias surgery. DESIGN, SETTING, AND PARTICIPANTS:
      Paediatric urologists, paediatric surgeons, urologists, and plastic surgeons
      worldwide were invited to participate an anonymous online questionnaire
      (http://www.hypospadias-center.info). MEASUREMENTS: General epidemiologic data,
      preferred technique in the correction of hypospadias, and preferred technique in
      the correction of penile curvature were gathered. RESULTS AND LIMITATIONS: Three
      hundred seventy-seven participants from 68 countries returned completed
      questionnaires. In distal hypospadias (subcoronal to midshaft), the tubularised
      incised plate (TIP) repair is preferred by 52.9-71.0% of the participants. Meatal
      advancement and glanuloplasty (MAGPI) is still a preferred method in glandular
      hypospadias. In the repair of proximal hypospadias, the two-stage repair is
      preferred by 43.3-76.6%. TIP repair in proximal hypospadias is used by 0.9-16.7%.
      Onlay flaps and tubes are used by 11.3-29.5% of the study group. Simple plication
      and Nesbit's procedure are the techniques of choice in curvature up to 30 degrees
      ; urethral division and ventral incision of the tunica albuginea with grafting is
      performed by about 20% of the participants in severe chordee. The frequency of
      hypospadias repairs does not influence the choice of technique. CONCLUSIONS: In
      this study, we identified current international trends in the management of
      hypospadias. In distal hypospadias, the TIP repair is the preferred technique. In
      proximal hypospadias, the two-stage repair is most commonly used. A variety of
      techniques are used for chordee correction. This study contains data on the basis
      of personal experience. However, future research must focus on prospective
      controlled trials.

PMID- 21871709
TI  - Contemporary role of prostate cancer antigen 3 in the management of prostate
      cancer.
AB  - CONTEXT: Newly discovered biomarkers ideally should prove clinical usefulness,
      provide additional detection, staging, and prognosis information to improve
      individual risk assessment, and potentially permit targeted cancer therapy.
      OBJECTIVE: To review, display, and evaluate the current evidence regarding the
      biologic and analytic approach of urinary prostate cancer gene 3 (PCA3) in
      prostate cancer (PCa) detection, staging, and prognosis, and its therapeutic
      potential. EVIDENCE ACQUISITION: A systematic and comprehensive Medline search
      was performed using the Medical Subject Headings search terms PCA3, DD3, UPM3,
      prostate cancer, cell-lines, prostate tissue, prostate biopsy, detection,
      diagnosis, radical prostatectomy, staging, grading, progression, and gene
      therapy. Results were restricted to English-language papers published within the
      period 1999-2011. EVIDENCE SYNTHESIS: The PCA3 gene is highly overexpressed in
      specific PCa cell lines and prostatic tumours. In 2006, a simple and robust urine
      test (Progensa) became commercially available. Despite its costs, prostate cancer
      antigen 3 (PCA3) is superior to prostate-specific antigen (PSA) and percent free
      PSA in the early detection of PCa. PCA3 improves the diagnostic accuracy of
      externally validated nomograms among men with an elevated PSA undergoing biopsy.
      PCA3 independently predicts low-volume disease and pathologically insignificant
      PCa but is not associated with locally advanced disease and is limited in the
      prediction of aggressive cancer. Preliminary data demonstrate that combining PCA3
      with other new biomarkers further improves diagnostic and prognostic accuracy.
      Finally, findings of the first PCA3-Gene-ViroTherapy study suggest therapeutic
      potential by exploiting PCA3 overexpression. CONCLUSIONS: PCA3, integrated in
      novel biopsy nomograms or risk stratification tools, can be used to counsel or
      confirm biopsy indications. If confirmed in further studies, using PCA3 together
      with established staging risk factors could assist clinicians in specific
      pretreatment decision making. So far no evidence for the usefulness of PCA3 in
      active surveillance programs has been presented.

PMID- 21871710
TI  - Paclitaxel in pretreated metastatic penile cancer: final results of a phase 2
      study.
AB  - BACKGROUND: Previously published preliminary findings showed promising activity
      of paclitaxel in chemotherapy-pretreated metastatic penile cancer. OBJECTIVE: To
      evaluate the activity and safety of paclitaxel in pretreated metastatic penile
      cancer. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five patients were enrolled in
      a single-arm phase 2 multicentre study and treated with 175 mg/m2 paclitaxel at 3
      wk intervals until disease progression or irreversible toxicity. MEASUREMENTS:
      The objective response rate was the primary end point. Safety, progression-free
      survival (PFS), and overall survival (OS) were secondary end points. RESULTS AND
      LIMITATIONS: Partial responses were observed in 20% (5 of 25 patients). Grade 1-2
      neutropenia, nausea, and oral mucositis were the most common side effects, noted
      in 13, 9, and 8 patients, respectively. Grade 3-4 neutropenia was reported in
      seven patients (28%). Median PFS was 11 wk (95% confidence interval [CI], 7-30);
      median OS was 23 wk (95% CI, 13-48). Median survival in responders was 32 wk (95%
      CI, 20-48). One limitation of our study was the limited accrual, which did not
      reach the target of 27 patients, due to the typical slow enrolment of a rare
      disease. CONCLUSIONS: Final results of this study demonstrate that paclitaxel is
      moderately active and well tolerated. Further trials, which may also explore the
      combination of paclitaxel with other agents, are required to confirm our
      findings.

PMID- 21871712
TI  - The prostate cancer unit: a multidisciplinary approach for which the time has
      arrived.

PMID- 21871713
TI  - Risk factors and outcomes of urethral recurrence following radical cystectomy.
AB  - BACKGROUND: Conflicting data exist regarding predictors of urethral recurrence
      (UR) following radical cystectomy (RC) as well as variables associated with
      survival in patients who experience UR. OBJECTIVE: To evaluate the incidence,
      risk factors, and outcomes of patients with UR. DESIGN, SETTING, AND
      PARTICIPANTS: We reviewed 1506 patients who underwent RC to identify patients
      with UR. Median follow-up after RC was 13.5 yr (interquartile range [IQR]: 10.5
      18.4). INTERVENTION: Urethrectomy. MEASUREMENTS: Cox proportional hazard
      regression models were used to analyze predictors of UR and evaluate factors
      associated with death from urothelial carcinoma (UC) in patients who experienced
      UR. Cancer-specific survival (CSS) for patients with UR, stratified according to
      the mode of diagnosis (abnormal urethral cytology vs symptoms), was estimated
      using the Kaplan-Meier method and compared with the log-rank test. RESULTS AND
      LIMITATIONS: UR was identified in 85 patients (5.6%) at a median of 13.3 mo (IQR:
      6.1-23.2) after RC, including 80 of 1243 (6.4%) who underwent cutaneous urinary
      diversion and 5 of 242 (2.1%) who received an orthotopic neobladder (p=0.002). On
      multivariate analysis, prostate involvement with UC (hazard ratio [HR]: 4.89;
      p<0.0001), bladder tumor multifocality (HR: 2.34; p=0.001), and orthotopic
      diversion (HR: 0.34; p=0.02) were significantly associated with the risk of UR.
      The 5-yr CSS after UR diagnosed by cytology was 80% versus 41% for patients who
      presented with symptoms (p<0.0001). Patients with symptomatic UR were noted to
      have significantly higher stage disease at urethrectomy (p=0.04) and tended
      toward an increased risk of death from UC (HR: 1.94; p=0.08). Limitations
      included retrospective study design. CONCLUSIONS: Prostate involvement with UC,
      tumor multifocality, and type of urinary diversion are significantly associated
      with UR following RC. Although UR is relatively uncommon, the detection of
      asymptomatic UR was associated with significantly lower stage disease and
      improved patient survival, suggesting the importance of continued postoperative
      evaluation of the urethra.

PMID- 21871711
TI  - Contemporary role of androgen deprivation therapy for prostate cancer.
AB  - CONTEXT: Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents
      one of the most effective systemic palliative treatments known for solid tumors.
      Although clinical trials have assessed the role of ADT in patients with
      metastatic and advanced locoregional disease, the risk-benefit ratio, especially
      in earlier stages, remains poorly defined. Given the mounting evidence for
      potentially life-threatening adverse effects with short- and long-term ADT, it is
      important to redefine the role of ADT for this disease. OBJECTIVE: Review the
      published experience with currently available ADT approaches in various
      contemporary clinical settings of PCa and reported serious treatment-related
      adverse events. This review addresses the level of evidence associated with the
      use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this
      paper discusses evolving approaches targeting androgen receptor signaling
      pathways and emerging evidence from clinical trials with newer compounds.
      EVIDENCE ACQUISITION: A comprehensive review of the literature was performed,
      focusing on data from the last 10 yr (January 2000 to July 2011) and using the
      terms androgen deprivation, hormone treatment, prostate cancer and adverse
      effects. Abstracts from trials reported at international conferences held in 2010
      and 2011 were also evaluated. EVIDENCE SYNTHESIS: Data from randomized controlled
      trials and population-based studies were analyzed in different clinical
      paradigms. Specifically, the role of ADT was evaluated in patients with
      nonmetastatic disease as the primary and sole treatment, in combination with
      radiation therapy (RT) or after surgery, and in patients with metastatic disease.
      The data suggest that in men with nonmetastatic disease, the use of primary ADT
      as monotherapy has not shown a benefit and is not recommended, while ADT combined
      with conventional-dose RT (<72Gy) for patients with high-risk disease may delay
      progression and prolong survival. The postoperative use of ADT remains poorly
      evaluated in prospective studies. Likewise, there are no trials evaluating the
      role of ADT in patients with biochemical relapses after surgery or RT. In
      patients with metastatic disease, there is a clear benefit in terms of quality of
      life, reduction of disease-associated morbidity, and possibly survival. Treatment
      with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist
      therapy, with and without antiandrogens has been associated with various serious
      adverse events, including cardiovascular disease, diabetes, and skeletal
      complications that may also affect mortality. CONCLUSIONS: Although ADT is an
      effective treatment of PCa, consistent long-term benefits in terms of quality and
      quantity of life are predominantly evident in patients with advanced/metastatic
      disease or when ADT is used in combination with RT (<72Gy) in patients with high
      risk tumors. Implementation of ADT should be evidence based, with special
      consideration to adverse events and the risk-benefit ratio.

PMID- 21871714
TI  - Primary central nervous system lymphoma with testicular metastasis.

PMID- 21871715
TI  - Nano-lead particle synthesis from waste cathode ray-tube funnel glass.
AB  - Waste cathode ray-tube (CRT) funnel glass is classified as hazardous waste since
      it contains high amount of lead. In the present study, a novel process for lead
      nanopowder synthesis from this type of glass was developed by combining vacuum
      carbon-thermal reduction and inert-gas consolidation procedures. The key trait of
      the process was to evaporate lead out of the glass to obtain harmless glass
      powder and synchronously produce lead nanoparticles. In the synthesis process,
      lead oxide in the funnel glass was firstly reduced to elemental lead, and
      evaporated rapidly in vacuum circumstance, then quenched and formed nano-size
      particles on the surface of the cooling device. Experimental results showed that
      temperature, pressure and argon gas flow rate were the major parameters
      controlling lead evaporation ratio and the morphology of lead nanoparticles. The
      maximum lead evaporation ratio was 96.8% and particles of 4-34 nm were
      successfully obtained by controlling the temperature, holding time, process
      pressure, argon gas flow rate at 1000 degrees C, 2-4h, 500-2000 Pa, 50-200
      ml/min, respectively. Toxicity characteristic leaching procedure (TCLP) results
      showed that lead leaching from the residue glass met the USEPA threshold.
      Accordingly, this study developed a practical and environmental-friendly process
      for detoxification and reclamation of waste lead-containing glass.

PMID- 21871716
TI  - Cancer risk assessment of polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs) in former agricultural soils of Hong Kong.
AB  - The major objective of this study was to evaluate the carcinogenic risk posed to
      humans through PBDEs and PCBs of changing agricultural land use for recycling of
      e-waste and open burning of municipal waste. Nine locations were selected to
      represent 6 different types of land use such as e-waste dismantling workshop (EW
      (DW)) and e-waste open burning site (EW (OBS)). The total concentrations for
      PBDEs and PCBs, and the bioaccessibility of PCBs were determined using Soxhlet
      extraction and in vitro simulated gastric solution, respectively. Both total and
      bioaccessible concentrations were subsequently used to establish the cancer risk
      probabilities in humans via ingestion, dermal contact and inhalation of soil
      particles. It was found that very low cancer risk in all 6 types of different
      land use was caused by BDE-209. Nevertheless, at the 95th centile, the
      concentration of PCBs in EW (DW) and EW (OBS) indicate a low cancer risk to
      humans of 40 and 2.1 in a million, respectively, while the same was also observed
      for the bioaccessible PCBs in EW (DW) of 1.71 +/- 2.96 in a million.

PMID- 21871717
TI  - Removal of sulphur mustard, sarin and simulants on impregnated silica
      nanoparticles.
AB  - Silica nanoparticles of diameter, 24-75 nm and surface area, 875 m(2)/g were
      synthesized using aero-gel route. Thereafter, nanoparticles were impregnated with
      reactive chemicals, and used as reactive adsorbent to study the removal of toxic
      nerve and blister chemical warfare agents and their simulants from solutions.
      Trichloroisocyanuric acid impregnated silica nanoparticles showed the best
      performance and indicated physisorption followed by chemisorption/degradation of
      toxicants. This indicated their suitability as universal decontaminant for nerve
      and blister agents. This system showed a decrease in t(1/2) from 1210 to 2.8 min
      for the removal of king of chemical warfare agents, i.e., sulphur mustard.
      Hydrolysis, dehydrohalogenation and oxidation reactions were found to be the
      route of degradation of toxicants over impregnated silica nanoparticles.

PMID- 21871718
TI  - Adsorption of volatile organic compounds by metal-organic frameworks MIL-101:
      influence of molecular size and shape.
AB  - Adsorption of gaseous volatile organic compounds (VOCs) on metal-organic
      frameworks MIL-101, a novel porous adsorbent with extremely large Langmuir
      surface area of 5870 m(2)/g and pore volume of 1.85 cm(3)/g, and the influence of
      VOC molecular size and shape on adsorption were investigated in this study. We
      observed that MIL-101 is a potential superior adsorbent for the sorptive removal
      of VOCs including polar acetone and nonpolar benzene, toluene, ethylbeznene, and
      xylenes. MIL-101 is of higher adsorption capacities for all selected VOCs than
      zeolite, activated carbon and other reported adsorbents. Adsorption of VOCs on
      MIL-101 is captured by a pore filling mechanism, showing the size and shape
      selectivity of VOC molecules. These prove to be a negative linear relationship
      between the volume adsorption capacities of VOCs and their molecular cross
      sectional area values. Most VOC molecules, such as acetone, benzene, toluene,
      ethylbenzene and p-xylene, enter into MIL-101 pores with the planes having the
      minimum diameters. However, m-xylene and o-xylene may fill into the pores with
      the planes having the maximum diameters because of the preferred interaction of
      MIL-101 with the two methyl groups of adsorbate molecules.

PMID- 21871719
TI  - Adsorption of cesium on cement mortar from aqueous solutions.
AB  - The adsorption of cesium on cement mortar from aqueous solutions was studied in
      series of bench-scale tests. The effects of cesium concentration, temperature and
      contact time on process kinetics and equilibrium were evaluated. Experiments were
      carried out in a range of initial cesium concentrations from 0.0103 to 10.88 mg
      L(-1) and temperatures from 278 to 313 K using coupons of cement mortar immersed
      in the solutions. Non-radioactive cesium chloride was used as a surrogate of the
      radioactive (137)Cs. Solution samples were taken after set periods of time and
      analyzed by inductively coupled plasma mass spectroscopy. Depending on the
      initial cesium concentration, its equilibrium concentration in solution ranged
      from 0.0069 to 8.837 mg L(-1) while the respective surface concentration on
      coupons varied from 0.0395 to 22.34 MUg cm(-2). Equilibrium test results
      correlated well with the Freundlich isotherm model for the entire test duration.
      Test results revealed that an increase in temperature resulted in an increase in
      adsorption rate and a decrease in equilibrium cesium surface concentration. Among
      several kinetic models considered, the pseudo-second order reaction model was
      found to be the best to describe the kinetic test results in the studied range of
      concentrations. The adsorption activation energy determined from Arrhenius
      equation was found to be approximately 55.9 kJ mol(-1) suggesting that
      chemisorption was the prevalent mechanism of interaction between cesium ions and
      cement mortar.

PMID- 21871720
TI  - Oxidative stress in earthworms short- and long-term exposed to highly Hg
      contaminated soils.
AB  - Exposure to mercury is often assessed by the measurement of molecular and
      biochemical antioxidant defences against an excessive production of reactive
      oxygen species. Here we examined some selected biomarkers of oxidative stress in
      the earthworm Lumbricus terrestris short- (2d) and long-term (44 d) exposed to Hg
      contaminated soils (up to 1287 mg/kg dry wt). This level of Hg exposure did not
      cause earthworm mortality, however it yielded organisms to a situation of
      oxidative stress which was evidenced by the time-dependent responses of
      biomarkers. The reduced to oxidized glutathione ratio was a sensitive and early
      biomarker of Hg exposure, although the glutathione reductase activity back
      returned their normal physiological concentrations. Metallothioneins and total
      glutathione seemed to have a significant role in reducing Hg-induced oxidative
      stress when exposure to Hg prolonged up to 44 d. We combined biomarker responses
      into an integrate biomarker index which positively correlated with the Hg
      concentrations measured in the postmitochondrial fraction of the earthworm
      muscle, and with the available Hg fraction in soil. Current results suggest that
      glutathione redox cycle can be a complementary tool in the exposure and effect
      assessment of Hg-polluted soils.

PMID- 21871721
TI  - Natural organic matter removal by adsorption onto magnetic permanently confined
      micelle arrays.
AB  - To remove natural organic matter (NOM) from water, magnetic permanently confined
      micelle arrays (Mag-PCMAs) were synthesized by coating the surface of Fe(3)O(4)
      particles with a silica/surfactant mesostructured hybrid layer. An environmental
      scanning electron microscope (ESEM) was used to characterize the particle size
      and surface morphology of the Mag-PCMAs. The zeta potential was used to assess
      the surface charge. Batch experiments were performed to investigate the
      adsorption of NOM by Mag-PCMAs. It was determined that NOM removal efficiency by
      Mag-PCMAs could be as high as 80% at a wide range of initial pH values (~ 6.0
      10.0). The adsorption isotherm was fitted well by a Langmuir model. Although
      Fe(3)O(4) had a high positive charge and Mag-PCMAs a small negative charge, Mag
      PCMAs had a higher removal efficiency of NOM than uncoated Fe(3)O(4) particles
      (which are also magnetic), which indicated that the adsorption of NOM onto Mag
      PCMAs was not dominated by electrostatic interactions. Possible mechanisms of the
      adsorption of NOM onto Mag-PCMAs were hydrophobic interactions and hydrogen
      bonding. It was feasible to reuse Mag-PCMAs after regeneration. These results
      indicate that Mag-PCMAs can be very attractive for the removal of NOM from
      aqueous matrices.

PMID- 21871722
TI  - Removal of cadmium, copper, nickel, cobalt and mercury from water by Apatite
      IITM: column experiments.
AB  - Apatite IITM, a biogenic hydroxyapatite, was evaluated as a reactive material for
      heavy metal (Cd, Cu, Co, Ni and Hg) removal in passive treatments. Apatite IITM
      reacts with acid water by releasing phosphates that increase the pH up to 6.5
      7.5, complexing and inducing metals to precipitate as metal phosphates. The
      evolution of the solution concentration of calcium, phosphate and metals together
      with SEM-EDS and XRD examinations were used to identify the retention mechanisms.
      SEM observation shows low-crystalline precipitate layers composed of P, O and M.
      Only in the case of Hg and Co were small amounts of crystalline phases detected.
      Solubility data values were used to predict the measured column experiment values
      and to support the removal process based on the dissolution of hydroxyapatite,
      the formation of metal-phosphate species in solution and the precipitation of
      metal phosphate. Cd(5)(PO(4))(3)OH(s), Cu(2)(PO(4))OH(s), Ni(3)(PO(4))(2)(s),
      Co(3)(PO(4))(2)8H(2)O(s) and Hg(3)(PO(4))(2)(s) are proposed as the possible
      mineral phases responsible for the removal processes. The results of the column
      experiments show that Apatite IITM is a suitable filling for permeable reactive
      barriers.

PMID- 21871723
TI  - Removal of arsenic and methylene blue from water by granular activated carbon
      media impregnated with zirconium dioxide nanoparticles.
AB  - This study investigated the effects of in situ ZrO(2) nanoparticle formation on
      properties of granulated activated carbon (GAC) and their impacts on arsenic and
      organic co-contaminant removal. Bituminous and lignite based zirconium dioxide
      impregnated GAC (Zr-GAC) media were fabricated by hydrolysis of zirconium salt
      followed by annealing of the product at 400  degrees C in an inert environment.
      Media characterization suggested that GAC type does not affect the crystalline
      structure of the resulting ZrO(2) nanoparticles, but does affect zirconium
      content of the media, nanoparticle morphology, nanoparticle distribution, and
      surface area of Zr-GAC. The arsenic removal performance of both media was
      compared using 5mM NaHCO(3) buffered ultrapure water and model groundwater
      containing competing ions, both with an initial arsenic C(0) ~ 120 MUg/L.
      Experimental outcomes suggested favorable adsorption energies and higher or
      similar adsorption capacities than commercially available or experimental
      adsorbents when compared on the basis of metal content. Short bed adsorber column
      tests showed that arsenic adsorption capacity decreases as a result of kinetics
      of competing ions. Correlation between the properties of the media and arsenic
      and methylene blue removal suggested that surface area and GAC type may be the
      dominant factors controlling the arsenic and organic co-contaminant removal
      performance of the fabricated Zr-GAC media.

PMID- 21871724
TI  - Degradation and formation of wood odorant beta-cyclocitral during permanganate
      oxidation.
AB  - The effect of permanganate oxidation on the formation and degradation of wood
      odorant beta-cyclocitral in water was investigated. Oxidation experiments were
      conducted for beta-cyclocitral prepared from pure chemicals and extracted from
      Microcystis aeruginosa. The data were simulated with appropriate kinetic rate
      models. The formation and degradation of beta-cyclocitral during the oxidation of
      beta-carotene were also monitored and modeled. The degradation of beta
      cyclocitral prepared from pure chemicals followed second-order kinetics with a
      rate constant of 91.7 +/- 2.4M(-1)s(-1), and that of the beta-cyclocitral
      precursor, beta-carotene, followed first-order kinetics with a rate constant of
      0.0054 +/- 0.0004 min(-1). During the oxidation of beta-carotene, beta
      cyclocitral was produced. The formation and degradation can both be simulated by
      first-order kinetics with respect to beta-carotene and beta-cyclocitral
      concentrations, respectively. The degradation rate of beta-cyclocitral produced
      from beta-carotene was found to be much slower than that for beta-cyclocitral
      obtained from pure chemicals, very likely due to a mass transfer limitation. The
      kinetic models were further employed to simulate the oxidation of beta
      cyclocitral in the presence of beta-carotene and for beta-cyclocitral extracted
      from M. aeruginosa, respectively. The models well predict/fit the experimental
      data, with rate constants similar to other experiments, indicating that the
      models may be used for simulating the formation and degradation of beta
      cyclocitral in water treatment systems.

PMID- 21871725
TI  - Vertically aligned Ag nanoplate-assembled film as a sensitive and reproducible
      SERS substrate for the detection of PCB-77.
AB  - Vertically aligned Ag nanoplate-assembled film has been achieved by spin-coating
      Ag seeds on an ITO substrate and subsequent electrodeposition in a mixed aqueous
      solution of AgNO(3) and citric acid. As sufficient hot spots are located in the
      deep gaps between the neighboring nanoplates across the whole substrate, the Ag
      nanoplate-assembled film shows strong Surface enhanced Raman scattering (SERS)
      effect, together with good signal reproducibility. Therefore, the Ag nanoplate
      assembled films were tried as robust, highly sensitive and reproducible SERS
      substrates for the rapid detection of 3,3',4,4'-tetrachlorobiphenyl (PCB-77) and
      a detection limit of about 10(-6)M was reached. For further reducing the
      detection limit, a layer of decanethiol was modified on the Ag nanoplate surface
      to capture the PCB-77 molecules efficiently, and a lower detection limit of 10(
      7)M was achieved. A linear dependence was found between the logarithmic
      concentrations of PCB-77 and the intensities of the fingerprint peaks.
      Furthermore, the Ag nanoplate-assembled film can also be used as a SERS substrate
      to distinguish characteristic peaks of different polychlorinated biphenyls (PCBs)
      in their mixed solutions. Therefore the vertically aligned Ag nanoplate-assembled
      film has potentials as effective SERS substrates in rapid and direct detection of
      trace PCBs.

PMID- 21871726
TI  - Chromate reduction in Fe(II)-containing soil affected by hyperalkaline leachate
      from chromite ore processing residue.
AB  - Highly alkaline (pH 12.2) chromate contaminated leachate (990 MUmol L(-1)) has
      been entering soils below a chromite ore processing residue disposal (COPR) site
      for over 100 years. The soil immediately beneath the waste has a pH of 11->12.5,
      contains 0.3->0.5% (w/w) chromium, and 45->75% of the microbially available iron
      is Fe(II). Despite elevated pH, a viable microbial consortium of Firmicutes
      dominated iron reducers was isolated from this COPR affected soil. Soil pH and Cr
      concentration decrease with distance from the waste. XAS analysis of soil samples
      indicated that Cr is present as a mixed Cr(III)-Fe(III) oxy-hydroxide phase,
      suggesting that the elevated soil Cr content is due to reductive precipitation of
      Cr(VI) by Fe(II). Microcosm results demonstrate the capacity of COPR affected
      soil to abiotically remove all Cr(VI) from the leachate within 40 days. In air
      oxidation experiments less than 2% of the total Cr in the soil was remobilised
      despite significant Fe(II) oxidation. XAS analysis after air oxidation showed no
      change in Cr-speciation, indicating the Cr(III)-containing phase is a stable long
      term host for Cr. This work suggests that reductive precipitation of Cr(VI) is an
      effective method of contaminant immobilisation in soils where microbially
      produced Fe(II) is present.

PMID- 21871727
TI  - Catalytic NOx removal by single-wall carbon nanotube-supported Rh nanoparticles.
AB  - Single-wall carbon nanotubes functionalized with polyethylene glycol and doped
      with Rh nanoparticles were prepared and tested as catalyst for NO(x) reduction.
      Gravimetric adsorption studies were employed to elucidate the mechanism of NO
      adsorption on the active surface sites and to determine the onset of the
      desorption of oxygen. These studies provided information about the reaction
      kinetics and the lifetime of the catalyst, as well as the NO scission onset
      temperature and abatement rate, thus making possible to predict the conversion
      and define the optimum reaction conditions for efficient NO removal. Catalytic
      experiments were performed under different operating conditions and feed
      compositions, such as under rich operation, in presence of oxygen, and in
      presence of reducing CO and hydrocarbons. The developed nanostructured catalyst
      exhibits enhanced activity at lower temperatures in comparison to that reported
      for other Rh-based catalytic systems, while data about feed composition effects
      and carbon support depletion provided operating conditions that suppress N(2)O
      formation and extent the catalyst lifetime.

PMID- 21871728
TI  - Extraction of phenol from aqueous solutions by means of supported liquid membrane
      (MLS) containing tri-n-octyl phosphine oxide (TOPO).
AB  - This paper deals with the liquid-liquid extraction and the facilitated transport
      through a supported liquid membrane (SLM) system of aqueous phenol using tri-n
      octyl phosphine oxide (TOPO) dissolved in an appropriate organic solvent. Phenol
      has been quantitatively extracted from aqueous acidic solutions using TOPO
      dissolved in kerosene as organic phase. The effect of TOPO concentration
      dissolved in kerosene on the extraction efficiency reveals that TOPO combined
      with phenol in the ratio of 1:1. Using a flat-sheet SLM (FSSLM) system, more than
      65% of the initial phenol content in the feed phase was extracted and stripped in
      a NaOH aqueous receiving phase. The important operational variables affecting the
      facilitated transport of phenol through the FSSLM system studied are
      concentration of TOPO, membrane viscosity, feed phase pH, initial phenol
      concentration, polymeric support type and membrane stability. Regardless of its
      comparatively low extraction efficiency of phenol, the SLM based on TOPO exhibits
      higher long-term stability as compared to tributyl phosphate (TBP). Elaborated
      SLM system retained its stability and initial performance during the 5 days long
      experiment contrary to the TBP-SLM system where a time dependent negative
      tendency (transport efficiency decline) was observed.

PMID- 21871729
TI  - Screening evaluation of the ecotoxicity and genotoxicity of soils contaminated
      with organic and inorganic nanoparticles: the role of ageing.
AB  - This study aimed to evaluate the toxicity and genotoxicity of soils, and
      corresponding elutriates, contaminated with aqueous suspensions of two organic
      (vesicles of sodium dodecyl sulphate/didodecyl dimethylammonium bromide and of
      monoolein and sodium oleate) and five inorganic nanoparticles (NPs) (TiO(2),
      TiSiO(4), CdSe/ZnS quantum dots, Fe/Co magnetic fluid and gold nanorods) to
      Vibrio fischeri and Salmonella typhimurium (TA98 and TA100 strains). Soil samples
      were tested 2h and 30 days after contamination. Suspensions of NPs were
      characterized by Dynamic Light Scattering. Soils were highly toxic to V.
      fischeri, especially after 2h. After 30 days toxicity was maintained only for
      soils spiked with suspensions of more stable NPs (zeta potential>30 mV or <-30
      mV). Elutriates were particularly toxic after 2h, except for soil spiked with
      Fe/Co magnetic fluid, suggesting that ageing may have contributed for degrading
      the organic shell of these NPs, increasing the mobility of core elements and the
      toxicity of elutriates. TA98 was the most sensitive strain to the mutagenic
      potential of soil elutriates. Only elutriates from soils spiked with gold
      nanorods, quantum dots (QDs) and TiSiO(4) induced mutations in both strains of S.
      typhimurium, suggesting more diversified mechanisms of genotoxicity.

PMID- 21871730
TI  - Removal of Cu(II) and Cr(VI) ions from aqueous solution using chelating fiber
      packed column: equilibrium and kinetic studies.
AB  - Herein, we demonstrate the adsorption process system with the diethylenetriamne
      coupled polyacrylonitrile fiber for the removal of Cu(II) and Cr(VI) ions in the
      aqueous solution. The synthesized chelating fiber showed a high adsorption
      capacity of 11.4 mequiv/g. Interestingly, the crystal growth of copper ions on
      the chelating fiber was observed during the adsorption process. The chelating
      fiber packed column showed the high performance of the removal of Cu(II) in the
      aqueous solution due to the distinct characteristic of the crystal growth of
      metal ions on the chelating fiber. After Cu(II) adsorption on the chelating
      fiber, the color of the fiber changed to light blue from yellow. The isotherm
      parameter n of 1.991 was obtained with Freundlich isotherm model for the
      adsorption equilibrium study which indicates that Cu(II) adsorption on the
      chelating fiber is very favorable due to n>1. The pseudo-first-order and pseudo
      second-order model equations were used for the kinetic study.

PMID- 21871731
TI  - Magnetic pollen grains as sorbents for facile removal of organic pollutants in
      aqueous media.
AB  - Plant materials have long been demonstrated to sorb organic compounds. However,
      there are no known reports about pollen grains acting as sorbents to remove
      hydrophobic organic compounds (HOCs) such as pesticides, polycyclic aromatic
      hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) from contaminated
      waters. We report a facile and effective method to remove HOCs from water using
      magnetized short ragweed (Ambrosia artemisiifolia) pollen grains. We dispersed
      the magnetized pollen grains in two different water samples - deionized (DI) and
      natural storm water to mimic real environmental conditions likely to be
      encountered during treatment. The magnetized pollen grains were readily separated
      from the aqueous media via a magnetic field after adsorption of the HOCs. We
      measured the adsorption of five representative HOCs (acenaphthene, phenanthrene,
      atrazine, diuron, and lindane) onto magnetized ragweed pollen in different
      aqueous matrices. We demonstrate that the adsorption capacity of the magnetized
      ragweed pollen can be regenerated to a large extent for reuse as a sorbent. Our
      results also indicate that the magnetized pollen grains are as effective as
      activated carbon (AC) in removing HOCs from both types of contaminated waters.
      The high HOC sorption of the ragweed pollen allows it to have potential
      remediation application in the field under realistic conditions.

PMID- 21871732
TI  - Hollow fiber supported liquid-phase microextraction using ionic liquid as
      extractant for preconcentration of benzene, toluene, ethylbenzene and xylenes
      from water sample with gas chromatography-hydrogen flame ionization detection.
AB  - A novel method has been developed for the analysis of benzene, toluene, ethyl
      benzene, and o-, m- and p-xylenes (BTEXs) in water using hollow fiber supported
      liquid-phase microextraction (HF-LPME) followed by gas chromatography-hydrogen
      flame ionization detection. Ionic liquid 1-butyl-3-methy-limidazolium
      hexafluorophosphate ([BMIM][PF(6)]) was acted as the extractant for extraction
      and preconcentration of BTEXs from aqueous samples, and a porous-walled
      polypropylene hollow fiber was utilized to stabilize and protect [BMIM][PF(6)]
      during the extraction process. Various parameters that affect extraction
      efficiency were investigated in detail, and the optimized experimental conditions
      were as follows: 8 MUL of [BMIM][PF(6)] as extraction solvent for the target
      analytes in 20 mL of sample solution, 30 min of extraction time, a stirring rate
      of 1400 rpm and 15% NaCl (w/v) in aqueous sample at 25 degrees C (ambient
      temperature). The recovery was found to be 90.0-111.5% with RSD (n=5) of 1.3
      5.4%, and the detection limits (S/N=3) were in the range of 2.7-4.0 MUg/L. The
      proposed method was simple, cheap, rapid, sensitive and environmentally benign,
      and could act as an alternative to techniques for BTEXs analysis with expensive
      instrumentations.

PMID- 21871733
TI  - Persistent pain after lymph node excision in patients with malignant melanoma is
      neuropathic.
AB  - Persistent postoperative pain is a common complication of surgery, including
      surgical interventions for cancer. So far, there is limited information about the
      prevalence and clinical characteristics of pain after lymph node biopsy and
      dissection in patients with malignant melanoma. In this study, a questionnaire
      was sent out to all surviving patients (n=402) after surgery for cutaneous
      malignant melanoma at the Aalborg Hospital Department of Plastic Surgery,
      Aalborg, Denmark. Of patients responding, sentinel node biopsy (SNB) and/or lymph
      node dissection (LND) was performed in 175 patients. All patients with pain and a
      control group were invited to a clinical examination. Altered sensation and pain
      were significantly more common after LND (82% and 34%, respectively) than after
      SNB (32% and 14%, respectively). In patients with LND, 12% reported at least
      moderate pain and 14% impact of pain on quality of life, while in patients with
      SNB, 3% reported at least moderate pain and 2% pain impact on quality of life.
      The most important predictor of pain was sensory abnormalities. At the clinical
      follow-up, 10 out of 12 patients with pain both met the criteria of the recently
      proposed grading system for probable neuropathic pain and used descriptors on the
      DN4 questionnaire suggestive of neuropathic pain. Different patterns of sensory
      profiles were observed in single patients, suggesting heterogeneous sensory
      processing within single patients. This study suggested that nerve injury was the
      main underlying mechanism of persistent pain after lymph node excision.

PMID- 21871735
TI  - Naso-pharyngeal mites Halarachne halichoeri (Allman, 1847) in Grey seals stranded
      on the NW Spanish Atlantic Coast.
AB  - In North Atlantic European waters, the nasal mite Halarachne halichoeri has been
      described affecting Grey seals (Halichoerus grypus) producing different levels of
      respiratory disease. This study provides data on the prevalence, clinical signs
      and produced macro-pathology of this parasite mite infecting juvenile wild Grey
      seals stranded in North-Western Spanish coast. Among the 25 seals examined during
      the study, a total of 19 had nasal mites in their respiratory upper ways,
      including adult and larval stages. This represented a percentage of prevalence of
      76 +/- 8.37. All the live positive seals presented a typical clinical
      symptomatology associated to upper respiratory tract infections. In dead positive
      seals, a light to intense sinusitis could be diagnosed macroscopically. The
      presence of the parasite in the nasal sinuses appears as the primary cause of the
      high respiratory tract symptomatology presented in most of the juvenile seals
      stranded in the north coast of Spain. Ultrastructural characterization by
      scanning electronic microscopy (SEM) has confirmed the taxonomic status of the
      mite. This identification of H. halichoeri represents the first description of
      the occurrence of this parasite in Southern Europe.

PMID- 21871734
TI  - The effect of catastrophizing and depression on chronic pain--a prospective
      cohort study of temporomandibular muscle and joint pain disorders.
AB  - Although most cases of temporomandibular muscle and joint disorders (TMJD) are
      mild and self-limiting, about 10% of TMJD patients develop severe disorders
      associated with chronic pain and disability. It has been suggested that
      depression and catastrophizing contributes to TMJD chronicity. This article
      assesses the effects of catastrophizing and depression on clinically significant
      TMJD pain (Graded Chronic Pain Scale [GCPS] II-IV). Four hundred eighty
      participants, recruited from the Minneapolis/St. Paul area through media
      advertisements and local dentists, received examinations and completed the GCPS
      at baseline and at 18-month follow-up. In a multivariable analysis including
      gender, age, and worst pain intensity, baseline catastrophizing (beta 3.79,
      P<0.0001) and pain intensity at baseline (beta 0.39, P<0.0001) were positively
      associated with characteristic of pain intensity at the 18th month. Disability at
      the 18-month follow-up was positively related to catastrophizing (beta 0.38,
      P<0.0001) and depression (beta 0.17, P=0.02). In addition, in the multivariable
      analysis adjusted by the same covariates previously described, the onset of
      clinically significant pain (GCPS II-IV) at the 18-month follow-up was associated
      with catastrophizing (odds ratio [OR] 1.72, P=0.02). Progression of clinically
      significant pain was related to catastrophizing (OR 2.16, P<0.0001) and
      widespread pain at baseline (OR 1.78, P=0.048). Results indicate that
      catastrophizing and depression contribute to the progression of chronic TMJD pain
      and disability, and therefore should be considered as important factors when
      evaluating and developing treatment plans for patients with TMJD.

PMID- 21871736
TI  - Hd86, the Bm86 tick protein ortholog in Hyalomma scupense (syn. H. detritum):
      expression in Pichia pastoris and analysis of nucleotides and amino acids
      sequences variations prior to vaccination trials.
AB  - The genus Hyalomma includes the most frequent tick species infesting livestock in
      North Africa, one of these species, Hyalomma scupense (syn. H. detritum) is
      particularly important due to its role in the transmission of tropical
      theileriosis to cattle (Theileria annulata infection). We have cloned and
      characterized the orthologs of the Bm86 gene from H. scupense strains collected
      over Tunisia in 2006 and 2009. The recombinant protein rHd86 was expressed in
      Pichia pastoris for vaccination purpose using a transcript from the 2006 strain.
      The rHd86 was then purified from the yeast culture supernatant by a filtration
      and a size exclusion process. It was recognized by specific anti-Bm86 antisera.
      An important extent of inter-specific diversity ranging from 35 to 40% was
      recorded between Hd86 and Bm86/Bm95 proteins whilst a very limited level of intra
      specific diversity (1.7%) occurred between the Hd86 vaccine candidate protein and
      its homologues from H. scupense strains collected in 2009. These results
      emphasise the need for assessing the efficacy against H. scupense and others
      important cattle Hyalomma species in Tunisia of our Hd86 vaccine candidate
      alongside with a Bm86 vaccine.

PMID- 21871737
TI  - Evidence for bovine parafilariosis in Italy: first isolation of Parafilaria
      bovicola (Tubangui, 1934) from autochthonous cattle.
AB  - In May and July 2010 and in March 2011, the presence of multiple bleeding nodules
      at the level of the neck, shoulders, withers, back and rump in five cattle from
      three herds in north-central Italy were observed. A diagnosis of parafilariosis
      was made. Fragments of adult females of Parafilaria bovicola could be identified
      from the derma of three to five bioptic extirpates. Larvated eggs and free larvae
      were observed in serohemorrhagic exudates. This paper is the first report of the
      occurrence of parafilariosis in Italy and subsequent to the various outbreaks
      reported, it can now be said that bovine parafilariosis is also currently present
      in Italy.

PMID- 21871738
TI  - Allopregnanolone infused into the dorsal (CA1) hippocampus increases prepulse
      inhibition of startle response in Wistar rats.
AB  - The hippocampus is a brain structure that has traditionally been associated with
      the pathophysiology and neuropathology of schizophrenia. Also, one of the animal
      models of schizophrenia most widely accepted and validated is the deterioration
      of prepulse inhibition (PPI). The hippocampus (both dorsal and ventral) seems to
      be a brain structure important for the PPI since it appears to contribute to
      sensorimotor gating. A possible role of neurosteroids in schizophrenia has
      recently been suggested, as clozapine and olanzapine treatments increase brain
      and plasma levels of the neurosteroid allopregnanolone (AlloP). The aim of the
      present work is to investigate the effects of the intrahippocampal administration
      of neurosteroids on prepulse inhibition. For this purpose, we have bilaterally
      injected AlloP (0.2 MUg/0.5 MUl) and pregnenolone sulphate (PregS, 5 ng/0.5 MUl)
      into the dorsal CA1 hippocampus, and we have evaluated PPI behavior. Results show
      that intrahippocampal AlloP increases PPI ability regardless of prepulse
      intensity (5, 10 or 15 db above background). Intrahippocampal PregS
      administration, at the dose tested, does not significantly affect PPI
      performance. The increase in PPI due to intrahippocampal AlloP administration
      points out the important role of the hippocampus in central sensorimotor gating
      mechanisms and on the effects of neurosteroids on this behavior. The present
      findings may contribute to the study of the neurobiological basis of
      schizophrenia.

PMID- 21871739
TI  - Lean meat prediction with HGP, CGM and CSB-Image-Meater, with prediction accuracy
      evaluated for different proportions of gilts, boars and castrated boars in the
      pig population.
AB  - Prediction equations for the percentage lean meat in pig carcasses in The
      Netherlands were derived for the Hennessy Grading Probe 7, Capteur Gras/Maigre-
      Sydel and CSB-Image-Meater. Because castrated males are expected to vanish from
      the Dutch pig population in the near future, accuracy of prediction was evaluated
      for different scenarios representing a wide range of different proportions for
      entire males, castrated males and females in the Dutch pig population. The
      prediction equations for the instruments are in compliance with the EC
      regulations for prediction accuracy for the different scenarios. So, these
      equations will remain valid when castrated males are (gradually) removed from the
      Dutch slaughter population. Results of this study are of interest for researchers
      from countries or areas contemplating the use of one of the aforementioned
      instruments. The statistical approach for evaluation of prediction accuracy is of
      particular interest when changes in proportions of important subpopulations in
      the target population are foreseen.

PMID- 21871740
TI  - Effect of Maillard reaction products on oxidation products in ground chicken
      breast.
AB  - Three amino acid-sugar solutions were adjusted to pH 8.0, heated and lyophilized
      prior to addition to ground chicken breast (GCB). GCB with no additives, GCB with
      0.01% BHT, GCB with 0.1 or 0.2mg/g glucose heated with arginine, valine, or
      histidine were prepared. Thiobarbituric acid reactive substances (TBARS),
      volatiles determined by gas chromatography, and Hunter L*, a* and b* values were
      monitored over nine days. Multiple linear regression models were used to
      determine the effects of the studied factors on the corresponding outcome
      variables. a* values of GCB ranged from 1.60 to 4.90 over nine days of storage.
      While Maillard reaction products (MRP) lowered oxidation compared to control, no
      significant difference in TBARS between MRP solutions heated for 8 or 24h was
      found. Further, 0.1mg/g heated glucose-valine mixture decreased aldehydes up to
      72.87%. Therefore, shelf-life of GCB could be extended using 0.1 or 0.2mg/g MRP.

PMID- 21871741
TI  - Prediction of total viable counts on chilled pork using an electronic nose
      combined with support vector machine.
AB  - The aim of this study was to predict the total viable counts (TVC) in chilled
      pork using an electronic nose (EN) together with support vector machine (SVM). EN
      and bacteriological measurements were performed on pork samples stored at 4 
      degrees C for up to 10 days. Bacterial numbers on pork were determined by plate
      counts on agar. Principal component analysis (PCA) was used to cluster EN
      measurements. The model for the correlation between EN signal responses and
      bacterial numbers was constructed by using the SVM, combined with partial least
      squares (PLS). Correlation coefficients for training and validation were 0.94 and
      0.88, respectively, which suggested that the EN system could be used as a simple
      and rapid technique for the prediction of bacteria numbers in pork.

PMID- 21871742
TI  - Biochemical and sensory changes in dry-cured ham salted with partial replacements
      of NaCl by other chloride salts.
AB  - The reduction of the content of sodium chloride in dry-cured ham was studied in
      to prevent the problems related to high sodium intake (i.e. the hypertension).
      One of the possibilities to reduce the sodium content is the partial replacement
      of sodium chloride by mixtures of potassium, magnesium and calcium chloride
      salts. The effect of two salting formulations (formulation II: 50% NaCl-50% KCl
      and formulation III: 55% NaCl, 25% KCl, 15 CaCl(2) and 5 MgCl(2)) on the protease
      activity through the dry-curing process and on the sensory characteristics of the
      final product was evaluated and compared to those of control hams (formulation I,
      100% NaCl). Sensory attributes were all affected in the hams containing CaCl(2)
      and MgCl(2) while hams containing 50% KCl and NaCl (formulation II) were better
      valued, except for the attribute taste probably due to the potassium contribution
      to bitter taste.

PMID- 21871743
TI  - Methods used in cross-cultural comparisons of vasomotor symptoms and their
      determinants.
AB  - Methodological differences among studies of vasomotor symptoms limit rigorous
      comparison or systematic review. Vasomotor symptoms generally include hot flushes
      and night sweats although other associated symptoms exist. Prevalence rates vary
      between and within populations, but different studies collect data on frequency,
      bothersomeness, and/or severity using different outcome measures and scales,
      making comparisons difficult. We reviewed only cross-cultural studies of
      menopausal symptoms that explicitly examined symptoms in general populations of
      women in different countries or different ethnic groups in the same country. This
      resulted in the inclusion of nine studies: Australian/Japanese Midlife Women's
      Health Study (AJMWHS), Decisions At Menopause Study (DAMeS), Four Major Ethnic
      Groups (FMEG), Hilo Women's Health Survey (HWHS), Mid-Aged Health in Women from
      the Indian Subcontinent (MAHWIS), Penn Ovarian Aging Study (POAS), Study of
      Women's Health Across the Nation (SWAN), Women's Health in Midlife National Study
      (WHiMNS), and Women's International Study of Health and Sexuality (WISHeS). These
      studies highlight the methodological challenges involved in conducting multi
      population studies, particularly when languages differ, but also highlight the
      importance of performing multivariate and factor analyses. Significant cultural
      differences in one or more vasomotor symptoms were observed in 8 of 9 studies,
      and symptoms were influenced by the following determinants: menopausal status,
      hormones (and variance), age (or actually, the square of age, age(2)), BMI,
      depression, anxiety, poor physical health, perceived stress, lifestyle factors
      (hormone therapy use, smoking and exposure to passive smoke), and acculturation
      (in immigrant populations). Recommendations are made to improve methodological
      rigor and facilitate comparisons in future cross-cultural menopause studies.

PMID- 21871744
TI  - Analysis of microtraces in invasive traumas using SEM/EDS.
AB  - Scanning electron microscopy in combination with energy-dispersive X-ray
      spectrometry (SEM/EDS) is a proven forensic tool and has been used to analyze
      several kinds of trace evidence. A forensic application of SEM/EDS is the
      examination of morphological characteristics of tool marks that tools and
      instruments leave on bone. The microtraces that are left behind by these tools
      and instruments on the bone are, however, often ignored or not noticed at all. In
      this paper we will describe the use of SEM/EDS for the analysis of microtraces in
      invasive sharp-force, blunt-force and bone-hacking traumas in bone. This research
      is part of a larger multi-disciplinary approach in which pathologists, forensic
      anthropologists, toolmark and microtrace experts work together to link observed
      injuries to a suspected weapon or, in case of an unknown weapon, to indicate a
      group of objects that could have been used as a weapon. Although there are a few
      difficulties one have to consider, the method itself is rather simple and
      straightforward to apply. A sample of dry and clean bone is placed into the SEM
      sample chamber and brightness and contrast are set such that bone appears grey,
      metal appears white and organic material appears black. The sample is then
      searched manually to find relevant features. Once features are found their
      elemental composition is measured by an energy dispersive X-ray spectrometer
      (EDS). This method is illustrated using several cases. It is shown that SEM/EDS
      analysis of microtraces in bone is a valuable tool to get clues about an unknown
      weapon and can associate a specific weapon with injuries on the basis of
      appearance and elemental composition. In particular the separate results from the
      various disciplines are complementary and may be combined to reach a conclusion
      with a stronger probative value. This is not only useful in the courtroom but
      above all in criminal investigations when one have to know for what weapon or
      object to look for.

PMID- 21871745
TI  - An assessment of the repeatability of pubic and ischial measurements.
AB  - Forensic anthropologists frequently use measurements of the human skeleton to
      determine sex and ancestry. Since the establishment of the Daubert criteria of
      admissibility of scientific evidence to court, methodologies used by
      anthropologists came under severe scrutiny. It is therefore important to ensure
      that the osteometric standards that are used in skeletal analyses are clearly
      explained, repeatable and reliable. Adams and Byrd (2002) found that measurements
      of the pelvis that originated from a point inside the acetabulum could not be
      repeated accurately. The purpose of this paper was to use three different sets of
      pubic and ischial measurements to establish whether they can be repeated with
      high precision between four different observers, and also by the observers
      themselves. Generally, high levels of repeatability were obtained, with intra
      class correlations (ICC) above 0.8. Pubic and ischial measurements using a point
      in the acetabulum as origin performed the worst (ICC values of 0.82 and 0.79
      respectively for inter-observer repeatability), whereas other methods performed
      better with ICC values above 0.9. It is advised that pubic and ischial
      measurements should be taken using the origin of the iliac blade as landmark.

PMID- 21871746
TI  - Fatal pulmonary thromboembolism. A retrospective autopsy study: searching for
      genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants)
      and dating the thrombus.
AB  - The accuracy of antemortem diagnosis of pulmonary embolism is within the range of
      just 10-30%, so representing one of the most frequent missed diagnosis in sudden,
      unexpected death. We describe 43 fatal cases of pulmonary embolism as confirmed
      by post-mortem examination. The aim of our study was to verify the systematic
      search for the most common genetic thrombophilias (Factor V Leiden (G1691A) and
      FII (G20210A) gene variants) and dating the thrombus. As a whole, 41 patients
      (95.3%) had at least one risk factor. Pre-existing symptoms are described just
      before fatal embolism in 18 (41.9%) out 43 patients. In 18 out of 43 (41.9%) it
      was not possible to find the thrombotic site. In 24 out of the remaining 25 cases
      the involvement of the deep veins of one leg was shown; in 1 case the thrombus
      was localised in the inferior caval vein. 10 (41.7%) were iliac vein thromboses,
      7 (29.1%) femoral, 2 (8.3%) popliteal, 3 (12.6%) posterior-tibial, 1 (4.1%)
      anterior-tibial and 1 (4.1%) peroneal vein thromboses. In our cohort of patients,
      4 (10%) out of 40 cases carried the 20210A prothrombin gene variant in
      heterozygosis. One (2.5%) out of 40 carried the Factor V Leiden (G1691A) gene
      variant in heterozygosis. Patients carrying these gene variants in homozygosis or
      carrying both were not present in our case-series. We strongly underline the
      relevance of a complete methodological approach, integrating clinical data by
      means of autopsy findings and histological study. On the contrary, investigating
      common inherited thrombophilia is not warranted.

PMID- 21871747
TI  - Laminin-5 immunohistochemical mapping for analysis of local extension in
      hypopharyngeal cancer: A preliminary report.
AB  - OBJECTIVE: Laminin-5 gamma2 chain (LNgamma2) plays an important role in cancer
      differentiation and migration. Using a novel immunohistochemical mapping
      technique to investigate whole mucosal strips of total laryngopharyngectomy
      specimens using iodine, H-E, and LNgamma2 stainings, we investigated the
      locoregional behavior of hypopharyngeal cancer. METHODS: Surgical specimens from
      two patients with pyriform sinus cancer were investigated. Three percent iodine
      was applied to the tumor-bearing laryngopharynx during surgery and photographed.
      Stainabilities of H-E and LNgamma2 on pathologic sections from all mucosal strips
      were scored and coordinated with the laryngopharyngeal photograph to illustrate
      the immunohistochemical map. RESULTS: In both patients, the main tumor of
      invasive squamous cell carcinoma was circumferentially surrounded by a
      superficial lesion characterized by high grade intraepithelial neoplasia that
      remained unstained by iodine. On LNgamma2 immunohistochemical mapping, the main
      tumor was demonstrated by Score 2 staining and the superficial lesion by a
      stronger Score 3 staining. CONCLUSIONS: The finding of neoplastic cells at the
      periphery demonstrating a higher potential than the cancer cells at the tumor
      center is suggestive of impending progression from neoplasia to carcinoma. The
      current preliminary report suggested morphological evidence of intraepithelial
      infiltration and lateral invasion in hypopharyngeal cancer.

PMID- 21871748
TI  - The mRNA of claudins is expressed in the endolymphatic sac epithelia.
AB  - OBJECTIVE: Claudins are a family of membrane proteins which localize to tight
      junctions (TJs). Recent studies have shown that claudins can form pores for ions
      in the TJs and regulate the permeability of epithelial paracellular ion
      transport. The endolymphatic sac (ES) is a part of the inner ear, absorbing the
      endolymphatic fluid. ES dysfunction may result in endolymphatic hydrops. In this
      study, we focused on the paracellular transport and examined claudin mRNA
      expression in the ES epithelia. MATERIALS AND METHODS: Total RNA was isolated
      from whole ES epithelia of rats by laser capture microdissection. RT-PCR was used
      to evaluate the expression of claudins. The expression of each claudin mRNA in
      the epithelial cells of rat ES was confirmed by in situ hybridization. RESULTS:
      RT-PCR indicated the expression of cldn2, cldn4, cldn6, cldn7, cldn9, cldn11,
      cldn12, and cldn14. The expression of these claudin mRNAs in the epithelial cells
      of rat ES was confirmed by in situ hybridization. CONCLUSION: We demonstrated
      mRNA expression of multiple claudins in the rat ES epithelia. These results in
      the ES epithelia were consistent with a role of claudins in paracellular ion
      transport.

PMID- 21871749
TI  - A perspective from magnetic resonance imaging findings of the inner ear:
      Relationships among cerebrospinal, ocular and inner ear fluids.
AB  - Visualization of endolymphatic hydrops has been performed using magnetic
      resonance imaging (MRI) after intratympanic or intravenous gadolinium (Gd)
      injection. Our recent findings indicate that just as the prevalence of
      asymptomatic glaucoma is greater than that of symptomatic glaucoma, there are
      also many cases of asymptomatic endolymphatic hydrops. It is assumed that the
      asymptomatic endolymphatic hydrops that precedes Meniere's disease is found more
      frequently using MRI than with other techniques. Gd in the inner ear moves into
      the cerebrospinal fluid (CSF) via the internal auditory meatus. Gd enhancement is
      also recognized in the ocular fluid after the intravenous Gd administration. In
      this paper, the relationships between CSF, ocular fluid and inner ear fluid are
      reviewed. The central nervous system, eye and inner ear contain specialized
      extracellular fluids that are essential for maintaining their function: CSF,
      ocular fluid consisting of vitreous humor and aqueous humor, and inner ear fluid
      consisting of perilymph and endolymph. Abnormal accumulation of or pressure
      elevation in these fluids is associated with hydrocephalus, glaucoma and
      Meniere's disease, respectively. The dura mater and the arachnoid membrane of the
      optic nerve canal and inner ear meatus are very close to the eye and the inner
      ear, respectively. It has been reported that low CSF pressure is associated with
      glaucoma and endolymphatic hydrops. In glaucoma and Meniere's disease, nerve
      damage to ganglion cells rather than damage of the sensory cells is directly
      associated with progression of the disease. Retinal ganglion cells in glaucoma
      and spiral ganglion cells in Meniere's disease are targets of the abnormal
      accumulation of, or increased pressure in, the extracellular fluid, just as
      neurons are damaged in hydrocephalus. Studies on hydrocephalus, glaucoma and
      Meniere's disease as a group may deepen our understanding of each disease.

PMID- 21871750
TI  - Endorectal 3D T2-weighted 1mm-slice thickness MRI for prostate cancer staging at
      1.5Tesla: should we reconsider the indirects signs of extracapsular extension
      according to the D'Amico tumor risk criteria?
AB  - PURPOSE: To evaluate the accuracy of a 3D-endorectal 1mm-thick slices MRI
      acquisition for local staging of low, intermediate and high D'Amico risk prostate
      cancer (PCa). MATERIALS AND METHODS: 178 consecutive patients underwent a
      multiparametric MRI protocol prior to radical prostatectomy (RP). T2W images were
      acquired with the 3D sampling perfection with application optimized contrasts
      using different flip angle evolutions (SPACE) sequence (5mn acquisition time).
      Direct and indirect MRI signs of extracapsular extension (ECE) were evaluated to
      predict the pT stage. The likelihood of SVI (seminal vesicle invasion) was also
      assessed. RESULTS: Histology showed ECE and SVI in 38 (21%) and 12 (7%) cases,
      respectively. MRI sensitivity and specificity to detect ECE were 55 and 96% if
      direct signs of ECE were used and 84 and 89% (p<0.05), if both direct and
      indirect signs were combined. D'Amico criteria did not influence MRI performance.
      Sensitivity and specificity for SVI detection were 83% and 99%. CONCLUSIONS: 3D
      data sets acquired with the SPACE sequence provides a high accuracy for local
      staging of prostate cancer. The use of indirect signs of ECE may be recommended
      in low D'Amico risk tumors to optimise patient selection for active surveillance
      or focal therapy.

PMID- 21871751
TI  - Optimization of coronary whole-heart MRA free-breathing technique at 3 Tesla.
AB  - Four different techniques for 3-T whole-heart coronary magnetic resonance
      angiography (MRA) using free-breathing three-dimensional segmented parallel
      imaging and adiabatic T2-preparation were assessed. Coronary MRA at 3 T is
      improved by shortening the acquisition window more than employing the highest
      spatial resolution. Double-oblique whole-heart acquisitions result in better
      overall image quality and allow for better delineation of the left anterior
      descending coronary artery. It is possible to attain shorter acquisition windows
      and a smaller voxel size at 3 T than previously reported at 1.5 T.

PMID- 21871752
TI  - Ultra performance liquid chromatography coupled with quadrupole time-of-flight
      mass spectrometric procedure for qualitative and quantitative analyses of
      nortriterpenoids and lignans in the genus Schisandra.
AB  - An ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of
      flight mass spectrometry (QTOF-MS) procedure is designed for the first
      simultaneous analysis of nortriterpenoids and lignans in Schisandra samples. The
      method consists of three individual mass spectrometric experiments, including the
      full scan MS, MS/MS experiment and in-source collision induced dissociation (CID)
      MS/MS, which enable the identification of diagnostic fragmentation pathways of
      nortriterpenoids and lignans. As such, a total of 6 nortriterpenoids and 10
      lignans were unequivocally identified, and one nortriterpenoid and 20 lignans
      were tentatively identified from different Schisandra samples within 12.5 min. In
      addition, 6 nortriterpenoids and 10 lignans were quantified in 48 samples of S.
      chinensis and S. sphenanthera using an extract ion chromatogram (XIC) of the full
      scan MS experiment. Dataset obtained from UPLC-MS was processed with principal
      component analysis (PCA) and orthogonal partial least squared discriminant
      analysis (OPLS-DA) to compare the difference between the two Schisandra species.

PMID- 21871753
TI  - Simple and rapid analysis of methyldibromo glutaronitrile in cosmetic products by
      gas chromatography mass spectrometry.
AB  - A simple and rapid gas chromatography (GC) method with mass spectrometry (MS)
      detection has been developed for the determination of methyldibromo
      glutaronitrile (MDBGN) in cosmetic products. The presence of this preservative in
      commercial cosmetic samples is prohibited since 2007 because of its allergenic
      properties. The analyzed products were opportunely diluted in methanol and MDBGN
      was separated by fused silica capillary column and detected by electron impact
      (EI)-MS in positive ionization mode with a total run time of 7 min. The assay was
      validated in the range 0.005-0.100 mg MDBGN per g of examined product with good
      determination coefficients (r(2)>=0.99) for the calibration curves. At three
      concentrations spanning the linear dynamic range of the calibration curves, mean
      recoveries were always higher than 95% for MDBGN in the tested cosmetics. This
      method was successfully applied to the analysis of cleansing gels, shampoo and
      solar waters to disclose the eventual presence of MDBGN illegally added in
      cosmetic products.

PMID- 21871754
TI  - Gas-phase derivatization via the Meerwein reaction for selective and sensitive LC
      MS analysis of epoxides in active pharmaceutical ingredients.
AB  - A gas-phase derivatization strategy is reported by using the gas-phase Meerwein
      reaction for rapid and direct LC-MS analysis of epoxides, which are potential
      genotoxic impurities (GTIs) in active pharmaceutical ingredients (APIs). This
      class-selective ion/molecule reaction occurs between epoxides and the
      ethylnitrilium ion (CH(3)-C=NH<->CH(3)-C=NH) that is generated by atmospheric
      pressure ionizations (when acetonitrile is used as the mobile phase). Density
      functional theory (DFT) calculations at the B3LYP/6-311+G(d,p) level show that
      the gas-phase Meerwein reaction is thermodynamically favorable. Commonly used
      atmospheric pressure ionization techniques including ESI, APCI and APPI were
      evaluated for optimal formation of the Meerwein reaction products. APCI appears
      to be the method of choice since it offers better sensitivity and more robust
      detection under typical LC-MS instrumentation conditions. Quantitative analysis
      of epoxides can be achieved by either single ion monitoring (SIM) or multiple
      reaction monitoring (MRM) of the Meerwein reaction products. We demonstrate
      herein quantitative analysis of two potential GTIs of SB797313 and SB719133 in
      APIs. The validated methods afford excellent linearity (r(2)>=0.999), sensitivity
      (LOD<=1 ppm by w/w in 10 mg/mL APIs) and recovery (ranging from 92% to 102%), as
      well as accuracy (<=2.8% difference) and precision (<=2.2% RSD) based on
      injections of six prepared standards. This novel strategy is particularly useful
      when a target analyte is difficult to be directly analyzed by LC-MS (e.g. due to
      poor ionization) or unstable in the course of solution-phase derivatization.

PMID- 21871755
TI  - Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular
      block in a time-dependent fashion.
AB  - OBJECTIVE: The composite effects of organophosphorus (OP)-cholinesterase (ChE)
      inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in
      acute OP-ChE inhibitor intoxication have not been evaluated in detail. We
      investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime
      (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of
      rocuronium. METHODS: Isometric twitch tensions of rat left phrenic nerve
      hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal
      stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing
      was used for statistical comparison, and P < .05 was accepted as significant.
      RESULTS: Rocuronium reduced the indirectly elicited twitch tensions in normal
      (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] MUM, mean [95%
      confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a
      concentration-dependent fashion. Paraoxon caused a rightward shift in the
      rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] MUM).
      The rightward shift was completely inhibited by previous copretreatment (IC(50),
      9.98 [9.77-10.20] MUM) and partially inhibited by simultaneous copretreatment
      (IC(50), 11.68 [11.45-11.91] MUM) with PAM but was not inhibited by subsequent
      copretreatment (IC(50), 13.69 [13.39-13.99] MUM) with PAM (P < .01, n = 6).
      Atropine did not influence the rightward shift (P < .01, n = 6). DISCUSSION:
      Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and
      the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when
      applied earlier. The time-dependent effect of PAM indicates that the preceding
      presence of PAM in proximity to ChEs before Pox is necessary for definite
      suppression of the Pox-induced ChE inhibition.

PMID- 21871756
TI  - Three-view bedside ultrasound for the differentiation of acute respiratory
      distress syndrome from cardiogenic pulmonary edema.
AB  - Bedside ultrasound is being increasingly used by emergency physicians (EPs) for
      the differentiation of acute dyspnea in critically ill patients. Lung ultrasound
      is emerging as a highly sensitive tool in diagnosing alveolar interstitial edema
      with the presence of diffuse "B-lines" arising from the pleural line. However,
      when used independently, lung ultrasound is unable to differentiate between
      cardiogenic and noncardiogenic causes of pulmonary edema. This case report
      describes a rapid 3-view or "triple scan" sonographic examination to
      differentiate acute respiratory distress syndrome (ARDS) from cardiogenic
      pulmonary edema.

PMID- 21871757
TI  - Refractory hypoxia in an HIV-infected patient--a diagnostic challenge.
AB  - A 39-year-old man with HIV presented to the emergency department for evaluation
      of dyspnea accompanied by fever, diffuse chest discomfort, dry cough, and fatigue
      for past 1 week. The patient described his dyspnea as exertional progressing over
      1 week to rest dyspnea. He was prescribed antiretroviral therapy but was
      noncompliant. He had no paroxysmal nocturnal dyspnea, orthopnea, rash, oral
      thrush, or diarrhea. His last record CD4+ lymphocyte count and HIV viral load
      were 43 cells/mm3 and 178,0000 copies/mL, respectively. Vital signs included a
      temperature of 101 degrees F, heart rate of 115 beats per minute, respiratory
      rate of 16 per minute, and pulse oxygenation of 91% on room air. Lung examination
      revealed decreased breath sounds bilaterally, and the remainder of the
      examination was unrevealing. Laboratory findings revealed leukocytosis and
      increased serum lactate dehydrogenase of 577 U/L (90-190 U/L), and chest
      radiograph showed a right lower lobe infiltrate and perihilar, bilateral
      interstitial infiltrates (Fig. 1A).

PMID- 21871758
TI  - Pseudorenal failure due to intraperitoneal bladder rupture after blunt trauma:
      usefulness of examining ascitic fluid sediment.
AB  - A 42-year-old man noted decreased urine output and visited our emergency
      department. He said that 3 days previously, he had gotten drunk and fallen down a
      set of stairs. Blood tests and abdominal contrast-enhanced computed tomography
      revealed no abnormalities. A serum creatinine level of 5.89 mg/dL led to a
      diagnosis of acute renal failure and his hospitalization. After admission, his
      ascitic fluid level gradually increased, suggesting urine leakage into the
      peritoneal cavity. Microscopic examination of his ascitic fluid sediment revealed
      the presence of hyaline casts enclosing renal tubular epithelial cells.
      Cystography demonstrated contrast medium leakage into the peritoneal cavity,
      which led to a diagnosis of bladder rupture. Examination of ascitic fluid
      sediment is simple and very useful for diagnosing bladder rupture.

PMID- 21871759
TI  - Hypokalemic paralysis in a professional bodybuilder.
AB  - Severe hypokalemia is a potentially life-threatening disorder and is associated
      with variable degrees of skeletal muscle weakness, even to the point of
      paralysis. On rare occasions, diaphragmatic paralysis from hypokalemia can lead
      to respiratory arrest. There may also be decreased motility of smooth muscle,
      manifesting with ileus or urinary retention. Rarely, severe hypokalemia may
      result in rhabdomyolysis. Other manifestations of severe hypokalemia include
      alteration of cardiac tissue excitability and conduction. Hypokalemia can produce
      electrocardiographic changes such as U waves, T-wave flattening, and arrhythmias,
      especially if the patient is taking digoxin. Common causes of hypokalemia include
      extrarenal potassium losses (vomiting and diarrhea) and renal potassium losses
      (eg, hyperaldosteronism, renal tubular acidosis, severe hyperglycemia, potassium
      depleting diuretics) as well as hypokalemia due to potassium shifts (eg, insulin
      administration, catecholamine excess, familial periodic hypokalemic paralysis,
      thyrotoxic hypokalemic paralysis). Although the extent of diuretic misuse in
      professional bodybuilding is unknown, it may be regarded as substantial. Hence,
      diuretics must always be considered as a cause of hypokalemic paralysis in
      bodybuilders.

PMID- 21871760
TI  - Liver trauma diagnosis with contrast-enhanced ultrasound: interobserver
      variability between radiologist and emergency physician in an animal study.
AB  - OBJECTIVE: The purpose of our study was to evaluate interobserver variability
      between the radiologist and emergency physician in detecting blunt liver trauma
      by conventional and contrast-enhanced ultrasound (US) (CEUS). METHODS: We created
      20 sites of blunt liver trauma in rabbits and performed conventional US and CEUS
      on the animals. A radiologist and an emergency physician independently evaluated
      the degree of liver trauma. Using contrast-enhanced computed tomography as a
      reference standard, the diagnostic performance of US and CEUS was calculated.
      Interobserver variability between radiologist and emergency physician was
      compared before and after contrast enhancement of US. RESULTS: Overall
      sensitivity and specificity for detecting liver trauma on conventional US,
      regardless of the degree of trauma, were 61.1% and 100% for the radiologist and
      50% and 100% for the emergency physician. On CEUS, the sensitivity and
      specificity were 94.4% and 100% for both the radiologist and emergency physician.
      The interobserver agreement between emergency physician and radiologist increased
      from 0.867 to 0.955 after contrast enhancement on US. CONCLUSIONS: Contrast
      enhanced US may permit a more accurate diagnosis for liver trauma than
      conventional US by both the radiologist and emergency physician. Contrast
      enhanced US may also reduce interobserver variability for this diagnosis.

PMID- 21871761
TI  - Supraventricular tachycardia induced by chocolate: is chocolate too sweet for the
      heart?
AB  - Conflicting studies have been published concerning the association between
      chocolate and cardiovascular diseases. Fewer articles have described the
      potential arrhythmogenic risk related to chocolate intake. We present a case of
      paroxysmal supraventricular tachycardia in a woman after consumption of large
      quantity of chocolate. A 53-year-old woman with no significant medical history
      presented to us with complaints of palpitations and shortness of breath after
      consuming large amounts of chocolate. Electrocardiogram showed supraventricular
      tachycardia at 165 beats per minute, which was restored to sinus rhythm after
      adenosine bolus injection. Electrophysiology studies showed atrioventricular
      nodal reentry tachycardia, which was treated with radiofrequency ablation.
      Chocolate contains caffeine and theobromine, which are methylxanthines and are
      competitive antagonists of adenosine and can have arrhythmogenic potential. Our
      case very well describes an episode of tachycardia precipitated by large amount
      of chocolate consumption in a patient with underlying substrate. There are
      occasional case reports describing association between chocolate, caffeine, and
      arrhythmias. A large Danish study, however, did not find any association between
      amount of daily caffeine consumption and risk of arrhythmia.

PMID- 21871762
TI  - Transcranial sonography in prehospital setting.

PMID- 21871763
TI  - Sublingual tissue perfusion improves during emergency treatment of acute
      decompensated heart failure.
AB  - OBJECTIVES: The aim of this study was to measure sublingual perfused capillary
      density (PCD) to assess sublingual microvascular perfusion during emergency
      department (ED) treatment of acute decompensated heart failure (ADHF). METHODS:
      This prospective, observational study enrolled ED patients with ADHF, measuring
      pre- and post-ED treatment PCD. Sidestream dark-field imaging was analyzed by 3
      investigators blinded to patient identifiers and time points. Patient
      demographics, ADHF etiology, serum brain natriuretic peptide, and hemoglobin were
      measured along with a visual analogue scale (VAS), which assessed patient
      baseline characteristics and response to ED treatment. A paired t test analyzed
      changes in PCD, mean arterial pressure (MAP), and patient assessment. Interrater
      variability was assessed with an intraclass correlation coefficient (ICC), with a
      P value <.05 considered significant for all testing. RESULTS: Thirty-six patients
      were enrolled with a mean time between pretreatment and posttreatment PCD (+/-SD)
      of 138 +/- 59 minutes and a hospital length of stay of 4.0 +/- 4.1 days. During
      this time, PCD increased (difference, 1.3 mm/mm(2); 95% confidence interval, 0.4
      2.1; P = .004), as did the MAP (P = .002), patient VAS score (P < .001), and
      observer VAS score (P < .001). There was no correlation between the change in PCD
      and time (R(2) = .016, P = .47), MAP (R(2) = .013, P = .54), or VAS scores. The
      ICC was 0.954. CONCLUSIONS: Sublingual tissue perfusion is diminished in ADHF but
      increases with treatment. It may represent a quantitative way to evaluate ADHF in
      the ED setting.

PMID- 21871764
TI  - Renal infarction in the ED: 10-year experience and review of the literature.
AB  - OBJECTIVE: We aimed to describe clinical and radiologic features of acute renal
      infarction (RI). METHODS: Clinical, computed tomography (CT), and laboratory
      findings were retrospectively reviewed for patients diagnosed from 1999 to 2009
      with CT proof of acute RI. Possible etiology of infarction was recorded. All
      available published series of RI were reviewed. RESULTS: Thirty-eight patients
      with acute RI met inclusion criteria; 127 cases of RI from 7 previous series were
      pooled for analysis. The most common symptoms were abdominal pain, flank pain,
      nausea, and vomiting. Leukocytosis (>10 * 10(9)/L) and elevated lactate
      dehydrogenase levels (>620 IU/L) were the most prominent laboratory findings.
      Computed tomography features included wedge-shaped hypodensities in the renal
      parenchyma in 35 (92%) and global renal ischemia in 3 (8%) patients; 13 patients
      (34%) had concomitant splenic infarction. The most common etiology was atrial
      fibrillation. Computed tomography determined the specific cause for RI in 5
      patients (13%) and a possible etiology in 17 (45%). Exact correlation with
      previous series was limited by methodological diversity. CONCLUSION: Renal
      infarction should be considered in the differential diagnosis of a patient
      presented to the emergency department with abdominal or flank pain. Laboratory
      workup should include lactate dehydrogenase levels. After ruling out stone
      disease, contrast-enhanced CT examination is essential for the diagnosis.

PMID- 21871765
TI  - Ultrasound diagnosis of acute thrombosis of an abdominal aortic aneurysm: a case
      report.
AB  - BACKGROUND: Point-of-care ultrasound is an effective and reliable method to
      diagnosis the presence of an abdominal aortic aneurysm. However, there has been
      limited literature regarding ultrasound diagnosis of acute aortic thrombosis.
      OBJECTIVE: Discuss a patient case with acute aortic thrombosis diagnosed by point
      of-care emergency ultrasound. Review common etiologies and treatment options in
      this rare diagnosis. CASE REPORT: A patient with a known abdominal aortic
      aneurysm presented with mottled lower extremities. Point-of-care ultrasound was
      utilized by her physicians to diagnose acute thrombosis of her abdominal aorta.
      With conservative treatment the patient survived to hospital discharge.
      CONCLUSION: Aortic thrombosis is a rare and devastating problem that can be
      diagnosed with point-of-care ultrasound.

PMID- 21871766
TI  - Serum intestinal fatty acid binding protein and phosphate levels in the diagnosis
      of acute intestinal ischemia: an experimental study in rabbits.
AB  - BACKGROUND: Acute intestinal ischemia is a serious clinical disorder with
      mesenteric infarction, which has high mortality. It is important to establish a
      biochemical marker for the early diagnosis of acute intestinal ischemia.
      OBJECTIVES: The aim of this experimental study was to assess the changes in the
      serum levels of intestinal fatty acid binding protein (IFABP) and phosphate by
      time using the acute intestinal ischemia model in rabbits. METHODS: In this
      study, 21 New Zealand rabbits were randomly divided into three groups. Blood
      samples were obtained at 0, 1, 3, and 6 h in the control group. Blood samples
      were obtained at 0, 1, 3, and 6 h in the sham group after simple laparotomy.
      Blood samples were obtained at the same hours in the ischemia group after simple
      laparotomy and ligation of the superior mesenteric artery. RESULTS: There was no
      significant difference between the control, the sham, and the ischemia groups in
      terms of serum IFABP levels at any time (p > 0.05). Serum phosphate levels
      significantly increased in the ischemia group (p < 0.001). Studies on IFABP have
      begun emerging in the literature, and there is no standard approach for the
      technique to measure the IFABP level. No studies on IFABP were found in the
      literature on rabbits. CONCLUSION: Based on our results, the role that IFABP
      levels play in the diagnosis of acute intestinal ischemia is unclear at this
      time. Serum phosphate levels continued to rise as the duration of ischemia was
      prolonged. These findings support the suggestion that serum phosphate levels are
      valuable for the diagnosis of acute intestinal ischemia.

PMID- 21871767
TI  - A woman with positional headache: a case of spontaneous intracranial hypotension.

PMID- 21871768
TI  - Traumatic rupture of a renal angiomyolipoma.

PMID- 21871769
TI  - Undiagnosed mental illness in the emergency department.
AB  - BACKGROUND: Mental illness affects 8% of the population. The early identification
      and treatment of mental illness can reduce the progression and complications of
      the illness. OBJECTIVE: The objective of this study was to identify unsuspected
      psychiatric illness in patients presenting to the emergency department (ED) with
      non-psychiatric-related complaints. A comparison of the test results and the
      emergency physician assessments were then compared. METHODS: All consenting and
      stable patients who presented to the ED with non-psychiatric complaints were
      given the Mini-International Neuropsychiatric Interview (MINI). It was
      administered to the patient by a trained research fellow before the patient was
      seen by the physician. Before the patient's departure from the ED, the research
      fellow notified the emergency physician of the results of the MINI interview.
      After the emergency physician was notified of the diagnosis of the MINI, any
      change in the treatment was reviewed. RESULTS: A total of 211 patients were
      enrolled in the study. The majority of patients (55%) tested negative for all
      undiagnosed mental illnesses. The top diagnoses were as follows: major depression
      (24%), general anxiety (9%), and drug abuse (8%). Of all those patients who
      tested positive for an undiagnosed mental illness, only 2% were diagnosed by the
      ED attending. CONCLUSIONS: The idea that the ED is a good place to identify
      undiagnosed mental health illnesses was confirmed. The use of an independent test
      such as the MINI was also shown to be useful to aid the emergency physician in
      identifying undetected mental illnesses.

PMID- 21871770
TI  - Client-Provider relationship in comprehensive substance abuse treatment:
      differences in residential and nonresidential settings.
AB  - As the substance abuse service system shifts from primarily residential to
      primarily nonresidential settings, it becomes important to understand how
      substance abuse treatment processes and outcomes may vary across service setting.
      Research increasingly indicates that, along with specific treatment and service
      strategies, client-provider relationship is an important ingredient in effective
      substance abuse treatment. This study uses a moderator-mediator analysis of a
      comprehensive service model to examine how the relation between client-provider
      relationship and substance abuse treatment outcomes may differ in residential and
      nonresidential settings. The study used data collected for the National Treatment
      Improvement Evaluation Study, a prospective, cohort-based study of U.S. substance
      abuse treatment programs and their clients, with an analytic sample of 59
      publicly funded service delivery units and 3,027 clients. Structural equation
      modeling is used to assess the structural relations and causal connections
      between treatment process and treatment outcome variables. Results indicate that
      for nonresidential settings, a better client-provider relationship is directly
      related to improved outcomes of treatment duration and reduced posttreatment
      substance use and is indirectly related to both outcomes through provision of
      services matched to client needs. In residential settings, the quality of the
      client-provider relationship is unrelated to process or outcome variables. The
      findings point to the importance of the client-provider relationship in all
      settings but particularly in outpatient settings where there are limited physical
      constraints on the treatment process.

PMID- 21871772
TI  - Carotid revascularization outcomes comparing distal filters, flow reversal, and
      endarterectomy.
AB  - INTRODUCTION: Contradictory outcomes exist for different methods of carotid
      artery revascularization. Here we provide the comparative rates of adverse events
      in patients after carotid endarterectomy (CEA), carotid artery stenting (CAS)
      with a distal embolic protection device (EPD), and CAS with a proximal flow
      reversal system (FRS) from a single institution by various specialists treating
      carotid artery disease. METHODS: Procedural billing codes and the electronic
      medical records of patients undergoing revascularization for carotid artery
      stenosis from February 2007 through March 2010 were used for data collection.
      Primary outcome was the incidence of cerebrovascular accident (CVA), myocardial
      infarction (MI), or death after CEA and CAS. Each practitioner determined the
      choice of therapy, with five of the 14 specialists providing both CAS and CEA.
      Baseline characteristics were examined for effect on outcome. Planned comparisons
      between and within groups were analyzed using chi(2), t tests, and analysis of
      variance, as appropriate. RESULTS: A total of 495 procedures were documented,
      comprising 226 CEA, 216 CAS with EPD, and 53 CAS with FRS. Preoperative
      comparisons of patient comorbidities were similar among the cohorts. The carotid
      artery stenosis was symptomatic in 42% of these patients. Prior CEA was an
      indication for CAS rather than another CEA (P < .001). Significantly fewer
      patients undergoing CEA were receiving preoperative antiplatelet therapy (P <
      .001). The groups did not differ significantly in the overall composite end point
      of death, CVA, and MI (4%, 5.1%, 0%; P = .1) or any individual major adverse
      event. Overall, patients undergoing CAS with EPD had a statistically significant
      greater incidence of minor CVAs than CEA patients (P = .031), which was driven by
      the increased CVA risk for asymptomatic patients. Secondary end points occurred
      rarely (<2%). There have been no reoperations or interventions in these patients
      to date within this institution. CONCLUSIONS: We have established a similar and
      low incidence of MI, CVA, and death among patients undergoing CEA and CAS, of
      whom approximately 40% were symptomatic. FRS provided superior results in this
      series; however, its use was limited to 20% of the CAS procedures. Still, zero
      adverse events in this cohort make FRS an exciting technology that warrants a
      large-scale prospective comparative study.

PMID- 21871773
TI  - Preprocedural imaging strategies in symptomatic carotid artery stenosis.
AB  - BACKGROUND: The benefit of carotid endarterectomy (CEA) over best medical therapy
      was established using intra-arterial angiography (IAA) for patient selection. Its
      cost, availability, and risk together with the emergence of newer imaging
      modalities have led to its replacement in the routine assessment of internal
      carotid artery (ICA) stenosis. The relative performance of these methods should
      dictate the optimum imaging strategy in symptomatic patients. METHODS: A previous
      meta-analysis (NIHR Health Technology Assessment Programme) was reviewed. Medline
      and PubMed search was performed for relevant publications since 2006 together
      with a review of the references in retrieved publications. RESULTS: Compared to
      IAA, the sensitivity and specificity for noninvasive imaging of a >=70% to 99%
      ICA stenosis are duplex ultrasound (DUS): 0.89 (0.85-0.92) and 0.84 (0.77-0.89);
      time-of-flight magnetic resonance angiography (TOF-MRA): 0.88 (0.82-0.92) and
      0.84 (0.76-0.97); contrast-enhanced MRA (CE-MRA): 0.94 (0.88-0.97) and 0.93 (0.89
      0.96); and computed tomography angiography: 0.77 (0.68-0.84) and 0.95 (0.91
      0.97), respectively. A policy of initial DUS followed by confirmatory CE-MRA best
      matches patient selection by arteriography. Single modality imaging for 50% to
      69% ICA stenoses suggests reduced reliability resulting in more inappropriate
      operations. CONCLUSIONS: DUS is the optimum screening tool due to its sensitivity
      and specificity, availability, and low cost. When CEA appears indicated,
      confirmatory imaging with CE-MRA is the most reliable and cost-effective method
      of investigation.

PMID- 21871774
TI  - Arthroscopic anatomy, variants, and pathologic findings in shoulder instability.
AB  - Shoulder instability is a common diagnosis that often requires surgical
      treatment. A detailed knowledge of the shoulder anatomy and its stabilizing
      structures is of utmost importance for successful treatment of shoulder
      instabilities. Identifying anatomic variants (e.g., sublabral hole, meniscoid
      labrum, cordlike middle glenohumeral ligament, and Buford complex) and
      distinguishing them from pathologic findings may be especially difficult, as
      shown by the high interobserver variability. Over the last decade, basic research
      and arthroscopic surgery have improved our understanding of the shoulder anatomy
      and pathology. In the context of shoulder instability, injuries of the glenoid
      (bony Bankart), injuries of the glenoid labrum superiorly (SLAP) or
      anteroinferiorly (e.g., Bankart, anterior labroligamentous periosteal sleeve
      avulsion, and Perthes), capsular lesions (humeral avulsion of the glenohumeral
      ligament), accompanying cartilage lesions (Hill-Sachs, glenolabral articular
      disruption), and rotator interval and pulley lesions, as well as signs of dynamic
      instability impingement (posterior-superior impingement, anterior-superior
      impingement) can be exactly diagnosed (magnetic resonance imaging with intra
      articular gadolinium, arthroscopy) and treated (arthroscopy). Therefore the
      purpose of this article is to review the current literature concerning shoulder
      anatomy/pathology related to shoulder stability/instability to improve clinical
      diagnosis and surgical treatment of our patients.

PMID- 21871775
TI  - Tirofiban use with clopidogrel and aspirin decreases adverse cardiovascular
      events after percutaneous coronary intervention for ST-elevation myocardial
      infarction: a meta-analysis of randomized trials.
AB  - Current guidelines deemed usefulness of routine early glycoprotein IIb/IIIa
      inhibitor (GPI) administration in ST-elevation myocardial infarction (STEMI)
      before primary percutaneous coronary intervention (PCI) with dual antiplatelet
      therapy as uncertain. We aimed to examine the current evidence for the use of
      tirofiban, a nonpeptide glycoprotein IIb/IIIa inhibitor, in STEMI patients
      treated with dual antiplatelet therapy. We performed systematic searches of
      MEDLINE, EMBASE, and CENTRAL databases for randomized controlled trials (RCTs) of
      tirofiban use in STEMI patients treated with aspirin and clopidogrel which
      reported clinical and/or angiographic outcomes after primary PCI. Data were
      combined using random effect and fixed effect models for heterogeneous and
      homogeneous outcomes respectively using Review Manager 5 (The Nordic Cochrane
      Centre, The Cochrane Collaboration, 2008). Six randomized controlled trials were
      eligible for the inclusion; involving 708 patients in tirofiban group and 721
      control subjects. Routine tirofiban use decreased the major adverse
      cardiovascular events (odds ratio [OR] 0.50; 95% confidence interval [CI], 0.26
      0.94). Corrected thrombolysis in myocardial infarction (TIMI) frame count was
      also reduced with tirofiban (mean difference -8.48 [95% CI, -12.62 to -4.34]).
      There were no significant differences in the rates of postprocedure TIMI flow
      grade 3 and TIMI myocardial perfusion/blush grade 3, major bleeding by TIMI
      criteria, or mortality in the 2 groups. Current analysis of available studies
      suggests that routine and early tirofiban use before primary PCI may decrease the
      major cardiovascular events in STEMI patients treated with aspirin and
      clopidogrel without any significant increase in major bleeding. An adequately
      powered randomized trial is urgently needed to confirm the above findings and
      estimate the effect size.

PMID- 21871776
TI  - Donor testing and risk: current prevalence, incidence, and residual risk of
      transfusion-transmissible agents in US allogeneic donations.
AB  - Over the past 20 years, there has been a major increase in the safety of the
      blood supply, as demonstrated by declining rates of posttransfusion infection and
      reductions in estimated residual risk for such infections. Reliable estimates of
      residual risk have been possible within the American Red Cross system because of
      the availability of a large amount of reliable and consistent data on donations
      and infectious disease testing results. Among allogeneic blood donations, the
      prevalence rates of infection markers for hepatitis C virus (HCV) and hepatitis B
      virus have decreased over time, although rates for markers of human
      immunodeficiency virus (HIV) and human T-cell lymphotropic virus did not. The
      incidence (/100 000 person-years) of HIV and HCV among repeat donors showed
      apparent increases from 1.55 and 1.89 in 2000 through 2001 to 2.16 and 2.98 in
      2007 through 2008. These observed fluctuations confirm the need for continuous
      monitoring and evaluation. The residual risk of HIV, HCV, and human T-cell
      lymphotropic virus among all allogeneic donations is currently below 1 per 1
      million donations, and that of hepatitis B surface antigen is close to 1 per 300
      000 donations.

PMID- 21871777
TI  - Red blood cell storage lesions and related transfusion issues: a Canadian Blood
      Services research and development symposium.
AB  - For centuries, man has been trying to figure out how to revive sick and
      traumatized individuals using fluids of various types, even from animals. In the
      17th century, it was determined that blood was the best fluid to use and, in the
      early 1900s, after the discovery of the ABO blood groups, human blood was found
      to provide significant benefit for patients with shock and/or anemia. In the
      1950s and 1960s, various ways to obtain, process, and store human blood were
      developed. It soon became apparent that storage of human blood for transfusion
      was problematic because red cells, as they aged in vitro, underwent a multitude
      of physicochemical changes that greatly affected their shelf life, the so-called
      storage lesion. More recently, the question has arisen as to the potential
      detrimental effects of the storage lesion and suggestions that older blood may
      induce increased morbidity and even mortality despite its acceptable in vivo
      survival. To address this issue of the efficacy and safety of transfusion of aged
      stored blood, a number of controlled clinical trials have been instituted to
      determine if older blood is significantly detrimental compared with fresher blood
      in transfusion recipients.

PMID- 21871778
TI  - Evaluating the role of blood collection centers in public health: a status
      report.
AB  - Blood centers have a central role in the community through recruitment and
      donation, and these community interactions enable blood centers to have a
      critical role in public health. Some public health initiatives are inherent in
      the blood center, such as providing human immunodeficiency virus educational
      material, whereas other initiatives have been actively created, such as
      cardiovascular screening, as a means to increase blood donor rates and increase
      the blood center's community interaction. These public health initiatives have
      been inconsistently practiced by blood collection centers over many years. An
      understanding of the current literature and exploring the potential role of blood
      centers in public health, while considering cost and value of these programs, are
      necessary for blood centers to evaluate the value of implementing these programs.
      The studies do not support a significant improvement in donor health or
      significant increase in donation rates through these public health initiatives.
      However, no study published thus far has been comprehensive enough or carried out
      long enough to adequately evaluate the value of providing health initiatives to
      donors.

PMID- 21871780
TI  - Effect of percutaneous transvenous mitral commissurotomy on left atrial appendage
      function: an immediate and 6-month follow-up transesophageal Doppler study.
AB  - BACKGROUND: The left atrial appendage (LAA) is a common site of thrombus
      formation and is the source of systemic thromboembolism in patients with
      rheumatic mitral stenosis. LAA contractile dysfunction is a common finding in
      these patients. The aim of this study was to assess immediate and 6-month follow
      up LAA function by transesophageal Doppler echocardiography in patients who
      underwent percutaneous transvenous mitral commissurotomy (PTMC). METHODS: Forty
      seven consecutive patients with symptomatic critical mitral stenosis who
      underwent PTMC were enrolled. All had underwent transthoracic and transesophageal
      echocardiography before, 24 hours after, and 6 months after PTMC. Pulse Doppler
      velocities of the LAA were measured, including peak early diastolic (E wave),
      peak late diastolic (A wave), and peak systolic (S wave). The corresponding
      tissue Doppler velocities of the LAA, including peak early diastolic (E(LAA)),
      peak late diastolic (A(LAA)), and peak systolic (S(LAA)), were also measured. LAA
      ejection fraction was measured using the modified Simpson's method. RESULTS: The
      mean age of the 47 enrolled patients was 31.7 +/- 10.26 years. Thirty-eight
      patients were in sinus rhythm, and the remaining nine were in atrial
      fibrillation. PTMC was successful in all patients. The pulse Doppler velocities
      of the LAA at baseline, after PTMC, and at 6-month follow-up were as follows: for
      the E wave, 15.29 +/- 2.26, 17.02 +/- 2.25, and 17.97 +/- 2.55 cm/sec,
      respectively (P < .001); for the A wave 22.45 +/- 4.11, 24.19 +/- 4.21, and 25.99
      +/- 4.51 cm/sec, respectively (P < .001); and for the S wave, 28.52 +/- 4.37,
      31.45 +/- 5.37, and 33.06 +/- 4.99 cm/sec, respectively (P < .001). The
      corresponding tissue Doppler velocities of LAA were as follows: for E(LAA), 4.65
      +/- 0.91, 5.28 +/- 0.85, and 5.80 +/- 0.84 cm/sec, respectively (P < .001); for
      A(LAA), 6.67 +/- 1.12, 7.33 +/- 1.17, and 7.88 +/- 1.22 cm/sec, respectively (P <
      .001); and for S(LAA), 4.67 +/- 1.12, 5.52 +/- 1.18, 6.07 +/- 1.11 cm/sec,
      respectively (P < .001). There was a nonsignificant increase in LAA ejection
      fraction (48.97 +/- 8.14% vs 52.3 +/- 13.76% vs 52.11 +/- 16.3%, respectively, P
      = .052). On subgroup analysis between patients in sinus rhythm and those with
      atrial fibrillation, there was no significant difference for LAA ejection
      fraction and pulse and tissue Doppler velocities. Very good intraclass
      correlation of the LAA parameters was also observed for the reproducibility of
      the data. CONCLUSIONS: The present study shows contractile dysfunction of the LAA
      in patients with critical mitral stenosis, which significantly improved after
      PTMC, and a further improvement was observed at 6-month follow-up. Favorable 6
      month improvements in LAA parameters suggest continuous structural remodeling of
      the LAA after PTMC, which is clinically attributed to the absence of
      thromboembolism. Although there was an improvement in LAA function, it was far
      below the normal range, suggesting a need for continuous long-term monitoring and
      management of thromboembolism in these patients.

PMID- 21871779
TI  - Stepping Stones Triple P seminars for parents of a child with a disability: a
      randomized controlled trial.
AB  - Parents of children with a developmental disability require tailored parenting
      support, as their families have special needs and are at risk of increased
      burden. The aim of this study was to evaluate the efficacy of the Stepping Stones
      Triple P seminars, a brief group intervention for parents of a child with a
      disability. There were two seminars that presented parenting strategies to
      improve both child behavior and parenting variables implicated in the development
      and maintenance of child problem behavior. Fifty-three parents participated in
      this randomized controlled trial. Each had a child, aged two to ten, with a
      disability. The results indicated significant reductions in child behavior
      problems, the use of dysfunctional parenting styles, and parental conflict
      reported by parents in the intervention group compared to a waitlist group. The
      results were maintained at 3-month follow-up and there was evidence of a sleeper
      effect for parenting confidence. This study demonstrated that the seminars
      provide a promising intervention for parents of children with a disability.
      Limitations and implications for future research are also discussed.

PMID- 21871781
TI  - Perfusion linearity and its applications in perfusion algorithm analysis.
AB  - Perfusion analysis computes blood flow parameters (blood volume, blood flow, and
      mean transit time) from the observed flow of a contrast agent passing through the
      patient's vascular system. Perfusion deconvolution has been widely accepted as
      the principal numerical tool for perfusion analysis, and is used routinely in
      clinical applications. The extensive use of perfusion in clinical decision-making
      makes numerical stability and robustness of perfusion computations vital for
      accurate diagnostics and patient safety. The main goal of this paper is to
      propose a novel approach for validating numerical properties of perfusion
      algorithms. The approach is based on the Perfusion Linearity Property (PLP),
      which is fundamental to virtually all perfusion data processing. PLP allows one
      to study perfusion values as weighted averages of the original imaging data.
      This, in turn, uncovers hidden problems with the existing perfusion techniques,
      and may be used to suggest more reliable computational approaches and
      methodology.

PMID- 21871782
TI  - Are postoperative intravenous antibiotics necessary after bimaxillary
      orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled
      clinical trial.
AB  - Postoperative antibiotic prophylaxis is often administered intravenously, despite
      an increased morbidity rate compared with oral application. This study
      investigates whether a postoperative oral antibiotic regimen is as effective as
      incorporation of intravenous antibiotics after bimaxillary orthognathic surgery.
      42 patients who underwent bimaxillary orthognathic surgery between December 2008
      and May 2010 were randomly allocated to 2 placebo-controlled postoperative
      antibiotic prophylaxis groups. Group 1 received oral amoxicillin 500mg three
      times daily; group 2 received intravenous ampicillin 1g four times daily, during
      the first two postoperative days. Both groups subsequently took oral amoxicillin
      for three more days. Clinically, the infection rate was assessed in both study
      groups for a period of 6 weeks after the surgery. 9 patients (21.4%) developed
      infection. No adverse drug event was detected. No significant difference (p=0.45)
      was detected in the infection rate between group 1 (3/21) and group 2 (6/21).
      Age, type of surgical procedures, duration of the operative procedure, surgical
      procedure-related events, blood loss, and blood transfusion were all found not
      related to infection (p>0.05). Administration of more cost-effective oral
      antibiotic prophylaxis, which causes less comorbidity, can be considered to be
      safe in bimaxillary orthognathic surgery with segmentalizations.

PMID- 21871784
TI  - Molecular characterisation of multiple drug-resistant Acinetobacter baumannii
      isolates in southern Taiwan.
AB  - The purpose of this study was to develop a multiplex polymerase chain reaction
      (mt-PCR) assay for synchronous detection of carbapenem resistance genes and/or
      pandrug resistance genes in clinical isolates of multidrug-resistant
      Acinetobacter baumannii (MDR-AB) and to investigate the association between the
      genetic make-up and a drug-resistant pattern. In total, 213 MDR-AB isolates were
      collected. All clinical isolates underwent antimicrobial susceptibility testing
      and were analysed for the presence of oxacillinase genes (bla(OXA-23), bla(OXA
      24), bla(OXA-51)-like and bla(OXA-58)), class A and C beta-lactamase genes
      (bla(TEM-1) and bla(AmpC), respectively), and an integron-associated antibiotic
      resistance gene (int1) by an in-house-designed mt-PCR assay. Of the 213 isolates,
      73.87% harboured both bla(TEM-1) and bla(AmpC) and 83.92% carried at least three
      oxacillinase genes. Moreover, 64.82% of the isolates were significant in that
      they had two beta-lactamase genes and three oxacillinase genes (P<0.001),
      indicating the complexity of the genetic make-up of carbapenem-resistant A.
      baumannii. The bla(OXA-51)-like allele was detected in the majority of these A.
      baumannii isolates (97.49%), whereas bla(OXA-23) was rarely prevalent in these
      isolates. In multivariate logistic regression, the presence of bla(OXA-23) and
      bla(TEM-1) had a statistically significant association with imipenem resistance
      [bla(OXA-23), P=0.004, odds ratio (OR)=10.52, 95% confidence interval (CI) 2.12
      52.17; bla(TEM-1), P=0.005, OR=6.14, 95% CI 1.74-21.62]. These results suggest
      that detecting bla(OXA-23) and bla(TEM-1) genes could be used to predict imipenem
      resistance in MDR-AB isolates. A mt-PCR for detecting carbapenem resistance genes
      and pandrug resistance genes of A. baumannii isolates was developed to provide an
      assay to quickly screen for potential imipenem-resistant A. baumannii in the
      clinic.

PMID- 21871783
TI  - Three-dimensional models of 14alpha-sterol demethylase (Cyp51A) from Aspergillus
      lentulus and Aspergillus fumigatus: an insight into differences in voriconazole
      interaction.
AB  - Aspergillus lentulus, an Aspergillus fumigatus sibling species, is increasingly
      reported in corticosteroid-treated patients. Its clinical significance is
      unknown, but the fact that A. lentulus shows reduced antifungal susceptibility,
      mainly to voriconazole, is of serious concern. Heterologous expression of cyp51A
      from A. fumigatus and A. lentulus was performed in Saccharomyces cerevisiae to
      assess differences in the interaction of Cyp51A with the azole drugs. The absence
      of endogenous ERG11 was efficiently complemented in S. cerevisiae by the
      expression of either Aspergillus cyp51A allele. There was a marked difference
      between azole minimum inhibitory concentration (MIC) values of the clones
      expressing each Aspergillus spp. cyp51A. Saccharomyces cerevisiae clones
      expressing A. lentulus alleles showed higher MICs to all of the azoles tested,
      supporting the hypothesis that the intrinsic azole resistance of A. lentulus
      could be associated with Cyp51A. Homology models of A. fumigatus and A. lentulus
      Cyp51A protein based on the crystal structure of Cyp51p from Mycobacterium
      tuberculosis in complex with fluconazole were almost identical owing to their
      mutual high sequence identity. Molecular dynamics (MD) was applied to both three
      dimensional protein models to refine the homology modelling and to explore
      possible differences in the Cyp51A-voriconazole interaction. After 20ns of MD
      modelling, some critical differences were observed in the putative closed form
      adopted by the protein upon voriconazole binding. A closer study of the A.
      fumigatus and A. lentulus voriconazole putative binding site in Cyp51A suggested
      that some major differences in the protein's BC loop could differentially affect
      the lock-up of voriconazole, which in turn could correlate with their different
      azole susceptibility profiles.

PMID- 21871785
TI  - Observation of "hidden" magnesium: first-principles calculations and 25Mg solid
      state NMR of enstatite.
AB  - (25)Mg NMR parameters have been determined for two polymorphs of enstatite
      (MgSiO(3)), an important magnesium silicate phase present as a major component of
      the Earth's upper mantle. The crystal structures of both polymorphs contain two
      crystallographically distinct magnesium sites; however, only a single resonance
      is observed in (25)Mg MAS NMR spectra recorded at 14.1 and 20.0 T. First
      principles calculations performed on geometry-optimised crystal structures reveal
      that the quadrupolar interaction for the second site is expected to be very
      large, resulting in extensive broadening of the spectral resonance, explaining
      its apparent absence in the NMR spectrum. (25)Mg QCPMG NMR experiments employing
      variable offset cumulative spectroscopy (VOCS) are used to observe the broadened
      site and enable measurement of NMR parameters. The large difference in
      quadrupolar interaction between the two crystallographic magnesium sites is
      rationalised qualitatively in terms of the distortion of the local coordination
      environment as well as longer-range effects using a simple point charge model.

PMID- 21871786
TI  - Preparation of thermoresponsive and pH-sensitivity polymer magnetic hydrogel
      nanospheres as anticancer drug carriers.
AB  - In this work, a novel thermo and pH responsive magnetic hydrogel nanosphere
      poly(N-isopropylacrylamide-co-acrylic acid)/Fe(3)O(4) (poly(NIPAAm-co
      AA)/Fe(3)O(4)) has been successfully prepared. The magnetic hydrogel nanospheres
      with thermo and pH-sensitivity were characterized by transmission electron
      microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared
      spectrometer (FT-IR), UV-vis absorption spectroscopy, and vibrating sample
      magnetometer (VSM). The magnetic hydrogel nanospheres exhibited uniform sphere
      structures and superparamagnetic property. Finally, the drug loading capacities
      and the releasing behavior of the magnetic hydrogel nanospheres were investigated
      with doxorubicin hydrochloride (DOX) as an anticancer drug model. The resulting
      magnetic hydrogel nanospheres exhibited high encapsulation efficiency (95%) to
      DOX under an appropriate condition. In vitro release experiments revealed that
      release was faster at pH 5.3 (37 degrees C) than at pH 7.4 (25 degrees C) or pH
      7.4 (37 degrees C). The DOX-loaded magnetic hydrogel nanospheres also showed
      enhanced anticancer effect compared with the free drug in vitro. These presented
      results suggested that the magnetic hydrogel nanospheres have a potential as
      tumor targeting drug carrier.

PMID- 21871787
TI  - Cloud point variation of amphiphilic drug promethazine hydrochloride with added
      surfactants.
AB  - In this paper we report clouding phenomenon occurring in an amphiphilic
      phenothiazine drug promethazine hydrochloride (PMT) in presence of surfactants.
      Cationic and nonionic surfactants increase the CP of 75 mM PMT solutions
      (prepared in 10 mM sodium phosphate buffer). These surfactants form mixed
      micelles with PMT. Anionic surfactants also form mixed micelles with the drug but
      the CP behavior is different by showing a peaked behavior. At low concentrations,
      anionic surfactants hinder micelle formation by forming ion-pairs whereas the
      usual CP decreasing effect at higher concentrations is due to mixed
      micellization. The CP behavior of 75 mM PMT+50 mM TBAB+surfactant systems is also
      explored which is found similar to PMT+surfactant systems with the difference
      only in magnitude of the clouding temperature.

PMID- 21871788
TI  - Radio Frequency Identification (RFID) and communication technologies for solid
      waste bin and truck monitoring system.
AB  - This paper deals with a system of integration of Radio Frequency Identification
      (RFID) and communication technologies for solid waste bin and truck monitoring
      system. RFID, GPS, GPRS and GIS along with camera technologies have been
      integrated and developed the bin and truck intelligent monitoring system. A new
      kind of integrated theoretical framework, hardware architecture and interface
      algorithm has been introduced between the technologies for the successful
      implementation of the proposed system. In this system, bin and truck database
      have been developed such a way that the information of bin and truck ID, date and
      time of waste collection, bin status, amount of waste and bin and truck GPS
      coordinates etc. are complied and stored for monitoring and management
      activities. The results showed that the real-time image processing, histogram
      analysis, waste estimation and other bin information have been displayed in the
      GUI of the monitoring system. The real-time test and experimental results showed
      that the performance of the developed system was stable and satisfied the
      monitoring system with high practicability and validity.

PMID- 21871789
TI  - The comparison of different gold nanoparticles/graphene nanosheets hybrid
      nanocomposites in electrochemical performance and the construction of a sensitive
      uric acid electrochemical sensor with novel hybrid nanocomposites.
AB  - In this paper, water soluble poly(diallyldimethylammonium chloride)-graphene
      nanosheets (PDDA-GNs) were synthesized and characterized by UV-visible absorption
      spectroscopy, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS).
      On the basis of PDDA-GNs, three different types of gold nanoparticles/graphene
      nanosheets (AuNPs/GNs) hybrid nanocomposites were obtained by one-pot synthesis,
      in situ reduction and adsorption methods, respectively. These nanocomposites were
      used as electrode materials for electrochemical determination of uric acid (UA).
      The results indicated adsorption to be the best method to synthesize hybrid
      nanocomposites from the electrochemical point of view. Given the fact positively
      charged PDDA-AuNPs could interact with negatively charged UA molecules, we then
      synthesized PDDA-protected gold nanoparticles/graphene nanosheets (PDDA
      AuNPs/GNs) hybrid nanocomposites by adsorption method, for the first time. As
      were expected, PDDA-AuNPs/GNs gave better performance for UA than AuNPs/GNs
      obtained by adsorption, and the anodic peak current of UA obtained by cyclic
      voltammetry (CV) increased 102.1-fold in comparison to bare GCE under optimizing
      conditions. Differential pulse voltammetry (DPV) was used to quantitatively
      determine UA. The linear range of UA was from 0.5MUM to 20MUM and the detection
      limit was 0.1MUM (S/N=3) with a high sensitivity of 103.08MUAMUM(-1)cm(-2). The
      assay results of urine sample provided satisfying recoveries by standard addition
      method. In addition, the anodic peaks of adrenaline (AD) and UA were well
      resolved at PDDA-AuNPs/GNs modified electrode, while they were too overlapped to
      separate at bare electrode, as a result of that UA was successfully detected in
      the presence of AD. In conclusion, rapid synthesis of PDDA-AuNPs/GNs were
      realized and applied as an advanced hybrid electrode material for UA
      determination.

PMID- 21871790
TI  - A label-free immunosensor based on modified mesoporous silica for simultaneous
      determination of tumor markers.
AB  - A label-free multiplexed immunoassay strategy was proposed for the simultaneous
      detection of two tumor markers, carcinoembryonic antigen (CEA) and alpha
      fetoprotein (AFP). Monoclonal antibody of CEA was co-immobilized with
      ferrocenecarboxylic acid (FCA) inside the channels of mesoporous silica (MPS) to
      prepare the label-free probe for CEA. Also, monoclonal antibody of AFP was co
      immobilized with horseradish peroxidase (HRP) inside the channels of MPS to
      prepare the label-free probe for AFP by using o-phenylenediamine (OPD) and
      H(2)O(2) as the electrochemical substrates. Thus, the multianalyte immunosensor
      was constructed by coating the probes of CEA and AFP respectively onto the
      different areas of indium-tin oxide (ITO) electrode. When the immunosensor was
      incubated with sample antigens, CEA and AFP antigens were introduced into the
      mesopores of MPS after the immunoassay reaction. Because all of the Si-OH groups
      on the external surface of MPS were blocked with Si(CH(3))(3), the proteins and
      substrates were limited to be embedded on the internal pore walls. Therefore, the
      electric response transfer was confined inside the pore channels. The
      nonconductive immunoconjugates blocked the electron transfer and the peak
      responses changed on the corresponding surface respectively. Then, the
      simultaneous detection of CEA and AFP achieved. The linear ranges of CEA and AFP
      were 0.5-45ngmL(-1) and 1-90ngmL(-1) with the detection limits of 0.2ngmL(-1) and
      0.5ngmL(-1) (S/N=3), respectively. The fabricated immunosensor shows appropriate
      sensitivity and offers an alternative to the multianalyte detection of antigens
      or other bioactive molecules.

PMID- 21871791
TI  - Dual-signal analysis eliminates requirement for milk sample pretreatment.
AB  - Detection of analytes in complex biological samples, such as milk and blood,
      normally requires sample pretreatment. These pretreatment regimes reduce assay
      throughput and increase testing costs. Technologies that make it possible to
      eliminate sample pretreatment are of great industrial interest. Here we report
      the development of a dual-signal flow injected analysis device which eliminates
      the need for sample pretreatment. The device employs thermal traducers to measure
      the signal from an enzyme and a reference column. This makes it possible to
      independently monitor and correct for non-specifically generated heat, thereby
      eliminating the need for sample pretreatment. The ability of the dual-signal
      device to determine urea and lactate in milk samples without any prior treatment
      was evaluated. The spiked milk samples, the urea assay had a linear range from
      0.1 to 50mM (R=0.996), and the lactate assay had a linear range from 0.025 to
      5.0mM (R=0.9998). The linear regression values for urea and lactate for 0.5%,
      1.5% and 3.0% fat milk were at least 0.990. The dual-signal design improves assay
      reproducibility, accuracy and sensitivity. Addition benefits are shorter assay
      times and lowers costs, as well as reducing equipment and training requirements.
      The potential application of the technology for multi-analyte analysis in point
      of care and decentralized diagnostic testing in healthcare, agriculture and
      environmental areas is discussed.

PMID- 21871792
TI  - Variation in surgical resection for lung cancer in relation to survival:
      population-based study in England 2004-2006.
AB  - BACKGROUND: Compared with some European countries, England has low lung cancer
      survival and low use of surgical resection for lung cancer. The use of surgical
      resection varies within England. We assessed the relationship between surgical
      resection rate and the survival of lung cancer patients in England. METHODS: We
      extracted data on 77,349 non-small cell lung cancer (NSCLC) patients diagnosed
      between 2004 and 2006 from the English National Cancer Repository Dataset. We
      calculated the frequency of surgical resection by age, socio-economic deprivation
      and geographical area. We used Cox regression to compute mortality hazard ratios
      according to quintiles of frequency of surgical resection amongst all 77,349 lung
      cancer patients, and separately for the 6900 patients who underwent surgical
      resection. RESULTS: We found large geographical variation in the surgical
      resection rate for NSCLC in PCT areas (3-18%). A high frequency of resection was
      strongly inversely associated with overall mortality (HR 0.88, 95% CI 0.86-0.91
      for the highest compared to the lowest resection quintile) and only moderately
      associated with mortality amongst the resected patients (HR 1.15, 95% CI 0.98
      1.36). Compared to the highest resection quintile, 5420 deaths could be delayed
      in the overall NSCLC group, whereas about 146 more deaths could be expected
      amongst the resected patients. CONCLUSION: The differences in the magnitudes of
      both the hazard ratios and the absolute excess deaths within resected patients
      and all NSCLC patients suggests that lung cancer survival in England could
      plausibly increase if a larger proportion of patients underwent surgical
      resection. Carefully designed research into the possible benefit of increasing
      resection rates is indicated.

PMID- 21871793
TI  - Bioregeneration of granular activated carbon in simultaneous adsorption and
      biodegradation of chlorophenols.
AB  - The objectives of this study are to obtain the time courses of the amount of
      chlorophenol adsorbed onto granular activated carbon (GAC) in the simultaneous
      adsorption and biodegradation processes involving 4-chlorophenol (4-CP) and 2,4
      dichlorophenol (2,4-DCP), respectively, and to quantify the bioregeneration
      efficiency of GAC loaded with 4-CP and 2,4-DCP by direct measurement of the
      amount of chlorophenol adsorbed onto GAC. Under abiotic and biotic conditions,
      the time courses of the amount of chlorophenol adsorbed onto GAC at various GAC
      dosages for the initial 4-CP and 2,4-DCP concentrations below and above the
      biomass acclimated concentrations of 300 and 150 mg/L, respectively, were
      determined. The results show that the highest bioregeneration efficiency was
      achieved provided that the initial adsorbate concentration was lower than the
      acclimated concentration. When the initial adsorbate concentration was higher
      than the acclimated concentration, the highest bioregeneration efficiency was
      achieved if excess adsorbent was used.

PMID- 21871794
TI  - Influences of light and oxygen conditions on photosynthetic bacteria
      macromolecule degradation: different metabolic pathways.
AB  - Direct degradation of macromolecules by photosynthetic bacteria (PSB) is
      important for the industrial application of PSB wastewater treatment. Light and
      oxygen are the most important parameters in PSB growth. This paper studied the
      PSB macromolecule degradation process under three different light and oxygen
      conditions: light-anaerobic, natural light-microaerobic and dark-aerobic. The
      results showed that under three different light-oxygen conditions, PSB
      degradation of macromolecules was higher than 90%; the removal ratios of COD, TN,
      TP, total sugar and protein were also high; and the biomass yield reached nearly
      0.5 mg-biomass/mg-COD-removal. Light and oxygen significantly influenced the
      efficiency. Macromolecules and pollutants removals were higher under oxygen
      condition than those under light-anaerobic condition. Theoretical analysis showed
      that under aerobic condition, PSB carried out oxidative phosphorylation, in which
      pollutants were sufficiently utilized with high mineralization degree. Under
      light-anaerobic condition, PSB carried out photophosphorylation and fermentation,
      which led to low pollutants removal efficiency.

PMID- 21871795
TI  - Silica-bonded N-propyl sulfamic acid used as a heterogeneous catalyst for
      transesterification of soybean oil with methanol.
AB  - The transesterification of soybean oil with methanol was carried out, to produce
      biodiesel, over silica-bonded N-propyl sulfamic acid in a heterogeneous manner.
      Results showed that a maximum conversion of 90.5% was achieved using a 1:20 M
      ratio of soybean oil to methanol and a catalyst amount of 7.5 wt.% at 423 K for
      60 h. It was found that the free fatty acid (FFA) and water present in the
      feedstock had no significant influence on the catalytic activity to the
      transesterification reaction. Besides, the catalyst also showed activities
      towards the esterification reaction of FFAs, in terms of the FFA conversion of
      95.6% at 423 K for 30 h. Furthermore, the catalyst could be recovered with a
      better reusability.

PMID- 21871796
TI  - Utilization of rice husks as a feedstock for preparation of activated carbon by
      microwave induced KOH and K2CO3 activation.
AB  - Rice husk (RH), an abundant by-product of rice milling, was used for the
      preparation of activated carbon (RHAC) via KOH and K(2)CO(3) chemical activation.
      The activation process was performed at the microwave input power of 600 W for 7
      min. RHACs were characterized by low temperature nitrogen adsorption/desorption,
      scanning electron microscopy and Fourier transform infrared spectroscopy. The
      adsorption behavior was examined using methylene blue as adsorbate. The K(2)CO(3)
      activated sample showed higher yield and better pore structures and adsorption
      capacity development than the KOH-activated sample, with a BET surface area,
      total pore volume and monolayer adsorption capacity of 1165 m(2)/g, 0.78 cm(3)/g
      and 441.52 mg/g, respectively. The results revealed the feasibility of microwave
      heating for preparation of high surface area activated carbons from rice husks
      via K(2)CO(3) activation.

PMID- 21871797
TI  - Effects of linker elongation in a series of N-(2-benzofuranylmethyl)-N'
      (methoxyphenylalkyl)piperazine sigma1 receptor ligands.
AB  - In our continued exploration of disubstituted piperazine derivatives as sigma
      (sigma) receptor ligands with central nervous system (CNS) activity, a series of
      N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazines (16-21 and 26-31)
      were synthesized, anticipating that these ligands would better suit the
      structural requirements of the current sigma(1) pharmacophore. Affinities of
      these ligands for sigma(1) and sigma(2) receptors were investigated by means of
      radioligand binding assays, with the identification of N-(2-benzofuranylmethyl)
      N'-[3-(4-methoxyphenyl)propyl]piperazine (29, K(i)=3.1 nM, sigma(2)/sigma(1)=45)
      as a selective sigma(1) ligand. The sigma(1) affinities and subtype selectivities
      of piperazines 16-21 and 26-31 were generally comparable to the corresponding
      benzylic analogs. Additionally, the affinities of 16-21 and 26-31 for the 5
      HT(2B) receptor were much lower than the relatively nonselective methoxybenzylic
      analogs 2-4, indicating that elongation of the alkyl tether generally improved
      selectivity for sigma(1) receptors.

PMID- 21871798
TI  - Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: from systemic to liver
      targeting inhibitors.
AB  - Optimization of a lead thiazole amide MF-152 led to the identification of potent
      bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In
      a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin
      and eyes where adverse effects were previously observed in rodents,
      representative systemically-distributed SCD1 inhibitors were converted into liver
      targeting SCD1 inhibitors.

PMID- 21871799
TI  - Mannich reaction derivatives of novobiocin with modulated physiochemical
      properties and their antibacterial activities.
AB  - Synthetic derivatives of the natural product antibiotic novobiocin were
      synthesized in order to improve their physiochemical properties. A Mannich
      reaction was used to introduce new side chains at a solvent-exposed position of
      the molecule, and a diverse panel of functional groups was evaluated at this
      position. Novobiocin and the new derivatives were tested for their binding to
      gyrase B and their antibacterial activities against Staphylococcus aureus,
      Mycobacterium tuberculosis, Francisella tularensis and Escherichia coli. While
      the new derivatives still bound the gyrase B protein potently (0.07-1.8 MUM,
      IC(50)), they had significantly less antibacterial activity. Two compounds were
      identified with increased antibacterial activity against M. tuberculosis, with a
      minimum inhibitory concentration of 2.5 MUg/ml.

PMID- 21871801
TI  - Imaging sensitivity of dedicated positron emission mammography in relation to
      tumor size.
AB  - Positron emission mammography (PEM) has been reported to have higher sensitivity
      than whole-body positron emission tomography (PET)due to higher spatial
      resolution. However, no direct evidence exists regarding the imaging sensitivity
      of PEM related to lesion size. In the present study, imaging sensitivity of PEM
      was investigated in relation to pathologically confirmed tumor size. A total of
      113 breast lesions from 101 patients were included in the analysis. The patients
      underwent (18)F-fluorodeoxyglucose (FDG) PEM and whole-body PET/computed
      tomography (CT) before surgical resection, and images were analyzed visually and
      quantitatively using the tumor-to-normal-tissue uptake ratio (TNR). Tumors were
      classified into four groups based on size using pathologic results, and
      sensitivities of PEM and PET/CT were compared in the overall subjects and in each
      size group. In visual analysis, PEM showed significantly higher imaging
      sensitivity than PET/CT (95% vs. 87%; P = 0.004), which was more definite in the
      small-tumor groups. In quantitative analysis, the TNR of PEM was significantly
      higher than that of PET/CT in the small-tumor groups, whereas no difference was
      found in the overall group. With a cutoff TNR of 2.5, PEM showed significantly
      higher sensitivity than PET/CT in the overall and small-tumor groups. In
      conclusion, PEM had higher imaging sensitivity than PET/CT, particularly in small
      tumors. The results suggest that PEM may be used for diagnosis and
      characterization of small lesions as a supplementary imaging modality for PET/CT.

PMID- 21871800
TI  - Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP)
      and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.
AB  - Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP)
      and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were
      designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication
      in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well
      as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values
      of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0,
      respectively, which were better than or comparable to those of the lead compound
      2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant
      inhibitory activity with an EC(50) of 128 nM and TI of 237.9.

PMID- 21871802
TI  - Breast cancer subtypes and outcomes of central nervous system metastases.
AB  - Central nervous system (CNS) metastases are detected in up to one third of
      patients with advanced breast cancer, but their incidence and outcomes by breast
      cancer subtypes are not precisely documented. Herein, we retrospectively analyzed
      clinicopathologic data of 259 breast cancer patients with CNS metastases to
      evaluate the association between breast cancer subtypes and CNS metastasis. The
      patient groups were classified according to their hormone receptor status and HER
      2 expression. Median follow-up time among the patients was 42 months and median
      survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing
      group, median time period between the diagnosis of breast cancer and the
      detection of CNS metastasis (15.9 months) was significantly shorter compared to
      the other groups (p = 0.01). The triple negative group had the shortest median
      survival time after CNS metastasis (6.6 months), although statistically not
      significant (p = 0.3). In multivariate Cox regression analyses, having solitary
      CNS metastasis (HR 0.4, 95% CI; 0.2-0.7, p = 0.004), and receiving chemotherapy
      after CNS metastasis (HR 0.4, 95% CI; 0.287-0.772, p = 0.003) were independent
      prognostic factors for increasing survival after CNS metastasis. In conclusion,
      new and effective treatment strategies are required for breast carcinoma patients
      with brain metastasis considering the positive effect of the treatment on
      survival.

PMID- 21871803
TI  - The F box protein partner of paired regulates stability of Drosophila centromeric
      histone H3, CenH3(CID).
AB  - Centromere identity and function is determined by the specific localization of
      CenH3 (reviewed in [1-7]). Several mechanisms regulate centromeric CenH3
      localization, including proteasome-mediated degradation that, both in budding
      yeast and Drosophila, regulates CenH3 levels and prevents promiscuous
      misincorporation throughout chromatin [8, 9]. CenH3(CENP-A) proteolysis has also
      been reported in senescent human cells [10] or upon infection with herpes simplex
      virus 1 [11]. Little is known, however, about the actual mechanisms that regulate
      CenH3 proteolysis. Recent work in budding yeast identified Psh1 as an E3
      ubiquitin ligase that mediates degradation of CenH3(Cse4p) [12, 13], but E3
      ligases regulating CenH3 stability in metazoans are unknown. Here, we report that
      the F box protein partner of paired (Ppa), which is a variable subunit of the
      main E3-ligase SCF [14-17], mediates CenH3(CID) stability in Drosophila. Our
      results show that Ppa depletion results in increased CenH3(CID) levels. Ppa
      physically interacts with CenH3(CID) through the CATD(CID) that, in the fly,
      mediates Ppa-dependent CenH3(CID) stability. Altogether, these results strongly
      suggest that, in Drosophila, SCF(Ppa) regulates CenH3(CID) proteolysis.
      Interestingly, most known SCF complexes are inactive when, at mitosis, de novo
      CenH3(CID) deposition takes place at centromeres, suggesting that, in Drosophila,
      CenH3(CID) deposition and proteolysis are synchronized events.

PMID- 21871805
TI  - The characterisation of workloads and nursing staff allocation in intensive care
      units: a descriptive study using the Nursing Activities Score for the first time
      in Norway.
AB  - OBJECTIVE: This study compares the Nine Equivalents of Nursing Manpower Use Score
      (NEMS) to the Nursing Activities Score (NAS) in terms of characterising the
      nursing workload by examining and calculating the per-nurse NAS% over a 24-h
      period. METHOD: The sample consisted of 235 patients from four volunteered for
      the study multidisciplinary ICUs in Norway. The daily NEMS, NAS and number of
      nurses who were involved in patient care per ICU were measured over one month
      from 2008 to 2009. RESULTS: The average length of stay for the included patients
      was 5 days, and the mean patient age was 52.8 years. The mean NEMS was 32.7
      points (S.D., 8.98 points), and the mean NAS was 96.24% (S.D., 22.35%). Several
      nurses exhibited mean NEMS points that ranged from 16 to 39.7 per ICU per day.
      The correlation between the NEMS and NAS could only be separately determined for
      each ICU. The correlation was r=0.16-0.40 [significant at the 0.01 level (2
      tailed)] per unit. Depending on which unit was investigated, each nurse was
      observed to perform of capacity with a NAS as high as 75-90%. CONCLUSION: The
      study suggests that the actual numbers of nurses might explain the calculated NAS
      of 75-90% per nurse.

PMID- 21871804
TI  - Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites
      in Drosophila.
AB  - Dendrites and axons show precise targeting and spacing patterns for proper
      reception and transmission of information in the nervous system. Self-avoidance
      promotes complete territory coverage and nonoverlapping spacing between processes
      from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell
      adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and
      accumulation of dendrites and axons, demonstrating a role in self-recognition and
      repulsion leading to self-avoidance [3-11]. Fasciculation and accumulation of
      processes suggested that Dscam1 might promote process spacing by counterbalancing
      developmental signals that otherwise promote self-association [9, 12]. Here we
      show that Dscam1 functions to counter Drosophila sensory neuron dendritic
      targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor.
      Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B
      expressing target, whereas concomitant loss of Frazzled prevented accumulation
      and caused severe deficits in dendritic territory coverage. Netrin misexpression
      was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent
      manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent
      with separable roles for these receptors. Our results suggest that Dscam1
      mediated self-avoidance counters extrinsic signals that are required for normal
      dendritic patterning, but whose action would otherwise favor neurite
      accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse
      contexts during neural circuit formation.

PMID- 21871806
TI  - Friend or foe: using systems biology to elucidate interactions between fungi and
      their hosts.
AB  - Modelling the networks sustaining the fruitful coexistence between fungi and
      their mammalian hosts is becoming increasingly important to control emerging
      fungal pathogens. In a 'systems biology' perspective, the microbiota and host
      should be seen as an ecosystem, and disease considered as an alteration of the
      equilibrium. This review addresses host-fungus interaction with a special focus
      on systems biology approaches to investigate the mechanisms developed by Candida
      albicans and Aspergillus fumigatus to circumvent host immune responses during
      fungal infections. Such genome-wide integrative approaches hold the promise to
      significantly improve our ability to understand which fungal traits can be
      considered potential threats and the regulatory networks involved in immune
      subversion.

PMID- 21871807
TI  - Applications of systems biology towards microbial fuel production.
AB  - Harnessing the immense natural diversity of biological functions for economical
      production of fuel has enormous potential benefits. Inevitably, however, the
      native capabilities for any given organism must be modified to increase the
      productivity or efficiency of a biofuel bioprocess. From a broad perspective, the
      challenge is to sufficiently understand the details of cellular functionality to
      be able to prospectively predict and modify the cellular function of a
      microorganism. Recent advances in experimental and computational systems biology
      approaches can be used to better understand cellular level function and guide
      future experiments. With pressure to quickly develop viable, renewable biofuel
      processes a balance must be maintained between obtaining depth of biological
      knowledge and applying that knowledge.

PMID- 21871808
TI  - Non-ketotic hyperglycemic chorea-hemiballismus mimicking basal ganglia
      hemorrhage.
AB  - Radiographic findings of hyperglycemic non-ketotic chorea-hemiballismus and basal
      ganglia hemorrhage can be highly similar. A 58-year-old female presented with a 1
      week history of choreiform and ballistic movements of the left arm. Based on CT
      imaging, the patient was diagnosed with a basal ganglia hemorrhage. After
      transfer to our institution, further imaging and work-up led to a diagnosis of
      non-ketotic hyperglycemic chorea-hemiballismus. Aggressive glycemic control was
      started and the patient's symptoms resolved. Despite its rarity, non-ketotic
      hyperglycemic chorea-hemiballismus should be included in the differential
      diagnosis of basal ganglia hyperdensity on CT scan, as it can mimic basal ganglia
      hemorrhage. Resolution of this clinical entity and implementation of aggressive
      glycemic control can lead to complete resolution of symptoms. It is important for
      neurosurgeons to be aware of this clinical entity as prompt treatment often
      yields good outcomes.

PMID- 21871809
TI  - Complement Factor H Y402H polymorphism is associated with an increased risk of
      mortality after intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) accounts for 10% to 15% of all strokes and is a
      major cause of morbidity and mortality. Despite advances in management, numerous
      clinical trials have failed to demonstrate significant benefit of medical and
      surgical interventions, underscoring the need for the identification of novel
      therapeutic targets based on improved understanding of ICH pathophysiology and
      optimal risk stratification based on reliable and effective prognosticators. The
      alternative complement cascade has been implicated as an important contributor to
      neurological injury after ICH. Therefore, common, functionally relevant genetic
      variants in the key components of this pathway have been associated with greater
      inflammation post-ictus, further cerebral damage, and ultimately, a worse
      outcome. We investigated the affects of single-nucleotide polymorphisms (SNP) on
      mortality in complement component 3 C3 (rs2230199), complement component 5 C5
      (rs17611), and Complement Factor H (CFH; rs1061170) genes, which are associated
      with the onset and progression of several neurological diseases, in a prospective
      cohort of patients with spontaneous ICH. From February 2009 through May 2010,
      adult patients with spontaneous ICH were admitted to the Columbia University
      Neurological Intensive Care Unit and enrolled in the Intracerebral Hemorrhage
      Outcomes Project. Demographic, clinical, radiographic, and treatment data were
      prospectively collected. Buccal swabs were obtained, and isolated cells were
      sequenced for the aforementioned SNP. A total of 103 patients were admitted with
      ICH, and of these, 82 consented for genetic testing and were included in the
      analysis. The median age was 61 years and 39% were females. The median Glasgow
      Coma Scale score on admission was 11.5. The CFH SNP was significantly associated
      with both discharge (p = 0.01) and 6-month mortality (p = 0.02), while no such
      association was observed for C3 (p = 0.545 and p = 0.830) or C5 (p = 0.983 and p
      = 0.536) SNP. Additionally, after controlling for pertinent variables identified
      in the univariate analysis, the CFH genotype independently predicted mortality at
      discharge (p = 0.019, odds ratio [OR] 7.62, 95% confidence interval [CI] 1.40
      41.6) and at 6 months (p = 0.041, OR 1.822, 95% CI 1.025-3.239). The CFH genotype
      was also independently predictive of survival duration (p = 0.041, OR 1.822, 95%
      CI 1.025-3.239). We concluded that CFH Y402H polymorphism independently predicts
      mortality at discharge and 6-months and survival duration after spontaneous ICH.

PMID- 21871810
TI  - Delayed post-traumatic capillary haemangioma of the spine.
AB  - Capillary haemangiomas are well-circumscribed aggregates of closely packed, thin
      walled capillaries separated by connective tissue stroma. In subcutaneous tissue
      they are termed pyogenic granuloma and commonly follow trauma. They rarely occur
      in the spine. We present a 43-year-old woman with a 6-week history of thoracic
      myelopathy and back pain on a background of T7 and T8 vertebral compression
      fractures from a motor vehicle accident 10 years previously. MRI demonstrated a
      posteriorly based extradural homogeneously enhancing mass at this level. The
      lesion was resected and diagnosed histopathologically as a capillary haemangioma.
      The patient's symptoms resolved and she made an uneventful recovery. The
      literature is reviewed and the possible pathogenesis is discussed.

PMID- 21871811
TI  - Effects of knee bracing on postural control after anterior cruciate ligament
      rupture.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To investigate the effects
      of functional knee braces on postural control in patients with anterior cruciate
      ligament (ACL) rupture. BACKGROUND: ACL rupture leads to both mechanical knee
      instability and deficits in proprioception. Although elastic knee braces do not
      increase mechanical stability, patients report improved stability when wearing a
      brace. Elastic braces were found to reduce the loss of proprioception. It is,
      however, still unclear whether they also improve postural control, which involves
      the processing of proprioceptive input at a higher level. METHODS: We studied 58
      patients with isolated unilateral ACL rupture using computerized dynamic
      posturography and compared overall stability index (OSI) scores for injured and
      uninjured legs with and without a knee brace. In addition, patients were
      classified as copers and non-copers depending on knee function. RESULTS: Within
      subjects, OSI scores were 3.0 +/- 1.1 degrees  for uninjured legs when unbraced,
      2.8+/-1.3 degrees  for uninjured legs when braced (p=0.17), 3.7 +/- 1.5 degrees 
      for unbraced injured legs, and 2.9 +/- 1.3 degrees  for braced injured legs
      (p<0.001). For the injured legs of copers and non-copers, OSI scores were 3.4
      degrees  +/- 1.2 degrees  for copers and 4.0 degrees  +/- 1.6 degrees  for non
      copers in the unbraced condition (p=0.11) and 2.7 +/- 1.0 degrees  for copers and
      3.1 +/- 1.4 degrees  for non-copers in the braced condition (p=0.26). CONCLUSION:
      Elastic knee braces increase postural stability by approximately 22% in patients
      with ACL rupture. There was no difference in postural stability between uninjured
      and injured legs in the braced condition. One possible explanation is that
      bracing improves both proprioception and postural control.

PMID- 21871812
TI  - Design and synthesis of 1,3-biarylsulfanyl derivatives as new anti-breast cancer
      agents.
AB  - A new series of 1,3-biarylsulfanyl derivatives (homodibenzyl core motif) have
      been designed and synthesized as new estrogen receptor ligands by chopping
      benzothiophene core of raloxifene to engender seco-raloxifene scaffold. All the
      synthesized compounds were screened for anti-proliferative, anti-osteoporotic,
      and anti-implantation activity. Compounds (35, 36) having basic amino anti
      estrogenic side chain were exhibiting potential anti-proliferative activity in
      MCF-7, MDA-MB-231 and ishikawa cell lines. Some of the synthesized compounds
      having homodibenzyl motif (5, 8, 10) have shown moderate anti-osteoporotic
      activity.

PMID- 21871813
TI  - The capture of phosphoproteins by 14-3-3 proteins mediates actions of insulin.
AB  - How does signalling via PI3K-PKB (AKT)-mTORC1-p70S6K and ERK-p90RSK mediate wide
      ranging physiological responses to insulin? Quantitative proteomics and
      biochemical experiments are revealing that these signalling pathways induce the
      phosphorylation of large and overlapping sets of proteins, which are then
      captured by phosphoprotein-binding proteins named 14-3-3s. The 14-3-3s are dimers
      that dock onto dual-phosphorylated sites in a configuration with special
      signalling and mechanical properties. They interact with the Rab GTPase
      activating proteins AS160 and TBC1D1 to regulate glucose uptake into target
      tissues in response to insulin and energy stress. Dynamic patterns in the 14-3-3
      binding phosphoproteome are providing new insights into how insulin triggers
      coherent shifts in metabolism that are integrated with other cellular response
      systems.

PMID- 21871814
TI  - Lysine-deficient lymphotoxin-alpha mutant for site-specific PEGylation.
AB  - The cytokine lymphotoxin-alpha (LTalpha) is a promising anticancer agent;
      however, its instability currently limits its therapeutic potential. Modification
      of proteins with polyethylene glycol (PEGylation) can improve their in vivo
      stability, but PEGylation occurs randomly at lysine residues and the N-terminus.
      Therefore, PEGylated proteins are generally heterogeneous and have lower
      bioactivity than their non-PEGylated counterparts. Previously, we created phage
      libraries expressing mutant LTalphas in which the lysine residues of wild-type
      LTalpha (wtLTalpha) were substituted for other amino acids. Here, we attempted to
      create a lysine-deficient mutant LTalpha with about the same bioactivity as
      wtLTalpha by using these libraries and site-specific PEGylation of the N
      terminus. We isolated a lysine-deficient mutant LTalpha, LT-K0, with almost
      identical bioactivity to that of wtLTalpha against mouse LM cells. The
      bioactivity of wtLTalpha decreased to 10% following random PEGylation, whereas
      that of LT-K0 decreased to 50% following site-specific PEGylation; PEGylated LT
      K0 retained five times the bioactivity of randomly PEGylated wtLTalpha. These
      results suggest that site-specific PEGylated LT-K0 may be useful in cancer
      therapy.

PMID- 21871815
TI  - Increased concentrations of IL-18 and uric acid in sickle cell anemia:
      contribution of hemolysis, endothelial activation and the inflammasome.
AB  - Sickle cell anemia (SCA) is a common, severe monogenetic disorder characterized
      by chronic hemolysis, frequent infections, a chronic inflammatory state and
      recurrent occlusions of the microcirculation, resulting in painful crises, organ
      damage and premature death. This study evaluated associations between serum
      levels of IL-18, uric acid, hemolytic markers, and inflammatory molecules in SCA
      patients. A cross-sectional study was performed including 45 SCA patients (median
      age of 20.5 years) without general symptoms and who had not undergone blood
      transfusions. Inclusion criteria for the steady-state SCA patients were the
      absence of hospitalization and the absence of infections. Interleukin-18 and uric
      acid levels were correlated closely with markers of hemolysis, endothelial
      dysfunction and others cytokines levels. These findings suggest probable
      influences of IL-18 and uric acid in the pathophysiology of vascular occlusion in
      SCA. Additional studies should be performed to characterize similar prognosis
      markers and possible therapeutic targets.

PMID- 21871817
TI  - Gamma irradiation of animal sera for inactivation of viruses and mollicutes--a
      review.
AB  - Animal-derived materials such as animal sera represent a low, but finite, risk
      for introduction of an adventitious agent (virus or mollicute) into a biological
      bulk harvest during upstream manufacturing processes involving mammalian cell
      substrates. Viral and mollicute (Mycoplasma sp. and Acholeplasma sp.)
      contamination events have been relatively rare, but many of those that have been
      reported have been attributed to use of infected animal sera in growth media
      during cell expansion. The risk of introduction of viruses and mollicutes may be
      mitigated by elimination of the use of animal sera and implementation instead of
      chemically defined or serum- and animal-derived material-free cell culture media.
      When use of animal sera is unavoidable, however, mitigation of the risk of
      introducing an adventitious contaminant may involve treatment of the sera to
      inactivate potential contaminants. Gamma irradiation is one of the most widely
      employed methods for viral and mollicute inactivation in animal sera. In this
      article, we review the inactivation results reported for viral and mollicute
      inactivation in frozen serum. Studies performed to assess the impact of gamma
      irradiation on serum quality and performance are also discussed. The available
      data indicate that inactivation of mollicutes in serum is essentially complete at
      the gamma radiation doses normally employed (25-40 kGy), while the efficacy and
      kinetics for viral inactivation in serum by gamma irradiation appear to be
      dependent in part upon the size of the target virus.

PMID- 21871816
TI  - The role of cytokines and chemokines in Histoplasma capsulatum infection.
AB  - Histoplasma capsulatum is a prevalent fungal pathogen in the United States,
      infecting approximately 500,000 individuals each year. Host protection requires
      an intact cell-mediated immune response. In this review, we will discuss how
      cytokines and chemokines influence protective immunity in H. capsulatum
      infection.

PMID- 21871818
TI  - Similar biological medicinal products currently licensed in the European union-
      overview of non-clinical study programs.
AB  - In the EU, a regulatory framework has been established which defines general
      conditions for marketing authorisation approval of similar biological medicinal
      products (SBMPs). In addition, the framework provides product-class specific
      recommendations for non-clinical evaluation of specific SBMPs containing as
      active substance recombinant somatropin, granulocyte-colony stimulating factor (G
      CSF), erythropoietin, interferon alpha, insulin or low molecular weight heparins.
      During the last years, a number of SBMPs have been succesfully licensed in the
      EU. This article summarizes the non-clinical evaluations performed for these
      medicinal products and provides a comparison with the current requests for non
      clinical evaluation as laid down in the respective EU regulatory guidelines.

PMID- 21871819
TI  - Renan Petrucci Uflacker, MD: 1949-2011.

PMID- 21871820
TI  - Comparison of serum KL-6 versus bronchoalveolar lavage neutrophilia for the
      diagnosis of bronchiolitis obliterans in lung transplantation.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a life-threatening
      complication after lung transplantation that is characterized by progressive
      fibrosis in the small airways. However, little is known about sensitive markers
      for detecting BOS. Our study compared the clinical utility of serum KL-6 level, a
      marker for pulmonary fibrosis, with that of neutrophilia in bronchoalveolar
      lavage fluid (BALF) for detecting BOS. METHODS: Levels of serum KL-6 were
      evaluated in 152 samples from 53 lung transplant recipients (BOS, 15; non-BOS,
      38) and in 27 samples from age- and sex-matched healthy individuals. Pulmonary
      function tests, arterial blood gas analysis, and BALF cell differentials were
      simultaneously evaluated. RESULTS: Serum KL-6 levels were significantly increased
      in the BOS group compared with the non-BOS group and the healthy individuals (p <
      0.0001). Receiver operating characteristic curve analysis for detecting BOS
      showed the largest area under the curve for KL-6 compared with lactate
      dehydrogenase, C-reactive protein, or neutrophils percentage in BALF. Serum KL-6
      correlated with the decline in forced expiratory volume in 1 second (FEV(1)) from
      post-lung transplant baseline (r = 0.43; p = 0.0001). CONCLUSIONS: Serum KL-6
      levels are increased and correlate with the decline from baseline in FEV(1) in
      lung transplant recipients. The diagnostic accuracy of serum KL-6 level is better
      than that of BALF neutrophilia for detecting BOS.

PMID- 21871821
TI  - Epilepsy in RAS/MAPK syndrome: two cases of cardio-facio-cutaneous syndrome with
      epileptic encephalopathy and a literature review.
AB  - We report two individual cases of cardio-facio-cutaneous (CFC) syndrome with
      severe neurological impairment consisting of infantile spasms with hypsarrhythmia
      and refractory epilepsy with multifocal epileptic paroxysms such as modified
      hypsarrhythmia. Both cases shared diffuse brain atrophy and severely delayed
      myelination on neuroimaging. Genetic analysis revealed individual heterozygous
      mutations in the KRAS (phenotype of CFC/Noonan syndrome) and BRAF genes
      (phenotype of CFC syndrome). Neurological impairment in cases with mutations in
      the RAS/MAPK (mitogen activated protein kinase) signal pathway may be more
      severe, and could be linked to some forms of refractory epilepsy, especially
      epileptic encephalopathy that includes infantile spasms.

PMID- 21871822
TI  - Postoperative morbidity index: a quantitative measure of severity of
      postoperative complications.
AB  - BACKGROUND: Postoperative complications are key outcomes of surgical procedures,
      but currently there is no uniform quantitative measure of complication severity.
      The purpose of this study was to evaluate and establish feasibility of
      quantitative morbidity scores for several common abdominal surgical procedures.
      STUDY DESIGN: Using American College of Surgeons' National Surgical Quality
      Improvement Program data, complications were identified in 5 common abdominal
      procedures for one institution in 2005-2008, including inguinal hernia,
      appendectomy, laparoscopic colectomy, hepatectomy, and pancreaticoduodenectomy.
      Complications were graded by the 6-level "expanded" Accordion Severity Grading
      System. Quantification was performed using severity scores described previously.
      RESULTS: Six hundred and seventy-six procedures were identified, including 88
      patients (13.84%) who had complications and 5 patients (0.79%) who died. After
      severity weighting, the postoperative morbidity index (PMI) for each procedure
      was derived. An index of 0 would indicate no complication in any patient and an
      index of 1.000 would indicate that all operated patients died. PMIs were hernia
      repair 0.005; appendectomy 0.031; laparoscopic colectomy 0.082; hepatectomy
      0.145; and pancreaticoduodenectomy 0.150. PMI of hepatectomy was greatly affected
      by the presence of a second procedure, ie, 0.070 without a second procedure and
      0.427 with a second procedure. Weighted severity spectragrams were developed,
      portraying the impact of each grade of complication on overall morbidity.
      CONCLUSIONS: Quantification of severity of postoperative complications is
      possible using American College of Surgeons' National Surgical Quality
      Improvement Program methods and the Accordion Severity Grading System. Procedural
      PMI can be useful in assessing surgical outcomes. Certain limitations,
      particularly the need for risk adjustment, still need to be addressed.

PMID- 21871823
TI  - Perioperative pharmacologic prophylaxis for venous thromboembolism in colorectal
      surgery.
AB  - BACKGROUND: To determine the effectiveness of pharmacologic prophylaxis in
      preventing clinically relevant venous thromboembolic (VTE) events and deaths
      after surgery. The Surgical Care Improvement Project recommends that VTE
      pharmacologic prophylaxis be given within 24 hours of the operation. The bulk of
      evidence supporting this recommendation uses radiographic end points. STUDY
      DESIGN: The Surgical Care and Outcomes Assessment Program is a Washington State
      quality improvement initiative with data linked to hospital admission/discharge
      and vital status records. We compared the rates of death, clinically relevant
      VTE, and a composite adverse event (CAE) in the 90 days after elective,
      colon/rectal resections, based on receipt of pharmacologic prophylaxis (within 24
      hours of surgery) at 36 Surgical Care and Outcomes Assessment Program hospitals
      (2005-2009). RESULTS: Of 4,195 (mean age 61.1 +/- 15.6 years; 54.1% women)
      patients, 56.5% received pharmacologic prophylaxis. Ninety-day death (2.5% vs
      1.6%; p = 0.03), VTE (1.8% vs 1.1%; p = 0.04), and CAE (4.2% vs 2.5%; p = .002)
      were lower in those who received pharmacologic prophylaxis. After adjustment for
      patient and procedure characteristics, the odds were 36% lower for CAE (odds
      ratio = 0.64; 95% CI, 0.44-0.93) with pharmacologic prophylaxis. In any given
      quarter, hospitals where patients more often received pharmacologic prophylaxis
      (highest tertile of use) had the lowest rates of CAE (2.3% vs 3.6%; p = 0.05)
      compared with hospitals in the lowest tertile. CONCLUSIONS: Using clinical end
      points, this study demonstrates the effectiveness of VTE pharmacologic
      prophylaxis in patients having elective colorectal surgery. Hospitals that used
      pharmacologic prophylaxis more often had the lowest rates of adverse events.

PMID- 21871824
TI  - Aortic stiffness and vitamin D are independent markers of aortic calcification in
      patients with peripheral arterial disease and in healthy subjects.
AB  - OBJECTIVE: Arterial stiffness is a significant determinant of cardiovascular risk
      and is related to vascular calcification. Vitamin D may regulate arterial
      calcification and has been associated with cardiovascular survival benefits.
      However, data about the relationship between arterial stiffness, aortic
      calcification and vitamin D levels in patients with peripheral arterial disease
      (PAD) and in healthy subjects are limited. We examined the potential association
      between aortic calcification, arterial stiffness and vitamin D levels in patients
      with symptomatic PAD and in healthy individuals. METHODS: We studied 78 men with
      PAD (aged 63 +/- 7 years) and 74 healthy men (aged 61 +/- 10 years). Aortic pulse
      wave velocity (aPWV) was determined by applanation tonometry using the Sphygmocor
      device. Aortic calcification score (ACS) was quantified by computed tomography.
      Serum 25-hydroxyvitamin D (25(OH)D) levels were measured using a radioimmune
      assay. RESULTS: ACS (4.9(2.3-8.9) vs. 0.2(0.03-1.6) (cm3); p < 0.01), aPWV (9.8
      +/- 2.4 vs. 8.2 +/- 1.6 (m s-1; p < 0.01) and 25(OH)D (15.1 +/- 5.4 vs. 19.0 +/-
      5.9 (ng ml-1); p < 0.01) were different in the patients compared with the
      controls. In multivariate analysis, ACS was independently determined by 25(OH)D,
      aPWV, calcium and age in patients with PAD (R2 = 0.49; p < 0.001) and by 25(OH)D,
      aPWV, cholesterol/high-density lipoprotein (HDL) and age in the control group (R2
      = 0.55; p < 0.001). Increased aPWV and lower levels of 25(OH)D were associated
      with decreased ankle-brachial pressure index (p = 0.03). CONCLUSION: These
      results indicate that calcification of the aorta is independently associated with
      aortic stiffness and serum 25(OH)D level in patients with PAD and in healthy
      subjects. Aortic stiffness and abnormal vitamin D level may contribute to
      vascular calcification and are related to higher severity grade of
      atherosclerotic disease.

PMID- 21871825
TI  - A novel N491S mutation in the human SLC11A2 gene impairs protein trafficking and
      in association with the G212V mutation leads to microcytic anemia and liver iron
      overload.
AB  - BACKGROUND: DMT1 is a transmembrane iron transporter involved in iron duodenal
      absorption and cellular iron uptake. Mutations in the human SLC11A2 gene coding
      DMT1 lead to microcytic anemia and hepatic iron overload, with unexpectedly low
      levels of plasma ferritin in the presence of iron stores. DESIGN AND METHODS: We
      report a patient with a similar phenotype due to two mutations in the SLC11A2
      gene, the known p.Gly212Val (G212V) mutation and a novel one, p.Asn491Ser
      (N491S). To assess the expression of DMT1 in human liver, we studied the
      expression of the four DMT1 mRNA isoforms by real-time quantitative PCR in
      control human liver samples. We also studied the effect of G212V and N491S DMT1
      mutations on RNA splicing in blood leukocytes and cellular trafficking of dsRed2
      tagged-DMT1 protein in the human hepatic cell line HuH7. RESULTS: Our results
      showed that i) only the isoforms 1B-IRE and 1B-nonIRE were significantly
      expressed in human liver; ii) the G212V mutation did not seem to affect mRNA
      splicing and the N491S mutation induced a splicing alteration leading to a
      truncated protein, which seemed quantitatively of low relevance; and iii) the
      N491S mutation, in contrast to the G212V mutation, led to abnormal protein
      trafficking. CONCLUSIONS: Our data confirm the major role of DMT1 in the
      maintenance of iron homeostasis in humans and demonstrate that the N491S
      mutation, through its deleterious effect on protein trafficking, contributes
      together with the G212V mutation to the development of anemia and hepatic iron
      overload.

PMID- 21871826
TI  - Overcoming apparent susceptibility-induced anisotropy (aSIA) by bipolar double
      pulsed-field-gradient NMR.
AB  - Double-Pulsed-Field-Gradient (d-PFG) MR is emerging as a powerful new means for
      obtaining unique microstructural information in opaque porous systems that cannot
      be obtained by conventional single-PFG (s-PFG) methods. The angular d-PFG MR
      methodology is particularly important since it can utilize the effects of
      microscopic anisotropy (MUA) and compartment shape anisotropy (csA) in the E(psi)
      profile at the different t(m) regimes to provide detailed information on
      compartment size and eccentricity. An underlying assumption is that the PFGs that
      are imparted to weigh diffusion are the only gradients present; however, in
      realistic systems and especially where there are randomly oriented anisotropic
      pores, susceptibility effects may induce strong internal gradients. In this
      study, the effects of such internal gradients on E(psi) plots obtained from
      angular d-PFG MR and on microstructural information that can be obtained from s
      PFG and d-PFG MR were investigated. First, it was found that internal gradients
      induce a bias in the s-PFG MR results, thus creating an anisotropy that is not
      related to microstructure, termed apparent-Susceptibility-Induced-Anisotropy
      (aSIA). We then show that aSIA effects are also manifest in different ways in the
      angular d-PFG MR experiment in controlled phantoms and in realistic systems such
      as quartz sand, emulsions, and biological systems. The effects of aSIA in some
      cases completely masked the effects of MUA and csA; however, we subsequently show
      that by introducing bipolar gradients to the d-PFG MR (bp-d-PFG), the effects of
      aSIA can be largely suppressed, restoring the E(psi) plots that are expected from
      the theory along with the microstructural information that it conveys. We
      conclude that when specimens are characterized by strong internal gradients, the
      novel information on MUA and csA that is manifest in the E(psi) plots can indeed
      be inferred when bp-d-PFG MR is used, i.e. when bipolar gradients are applied.

PMID- 21871827
TI  - SIRT1 is associated with a decrease in acute insulin secretion and a sex specific
      increase in risk for type 2 diabetes in Pima Indians.
AB  - Genetic variation in SIRT1 affects obesity-related phenotypes in several
      populations. The purpose of this study was to determine whether variation in
      SIRT1 affects susceptibility to obesity or type 2 diabetes in Pima Indians, a
      population with very high prevalence and incidence rates of these diseases.
      Genotypic data from single nucleotide polymorphisms (SNPs) identified by
      sequencing regions of SIRT1 combined with SNPs in/near SIRT1 from a prior genome
      wide association study determined that 4 tag SNPs (rs7895833, rs10509291,
      rs7896005, and rs4746720) could capture information across this gene and its
      adjacent 5' region. The tag SNPs were genotyped in a population-based sample of
      3501 Pima Indians (44% had diabetes, 58% female) for association with type 2
      diabetes and BMI. Metabolic trait data and adipose biopsies were available on a
      subset of these subjects. Two tag SNPs, rs10509291 and rs7896005, were nominally
      associated with type 2 diabetes (P=0.01, OR=1.25 95%CI 1.05-1.48, and P=0.02,
      OR=1.17 95%CI 1.02-1.34, respectively; additive P values adjusted for age, sex,
      birth year, and family membership), but not BMI (adjusted P values 0.52 and 0.45,
      respectively). Among metabolically characterized subjects with normal glucose
      tolerance (N=243), those carrying the diabetes risk allele (T) for rs10509291 and
      (G) for rs7896005 had a reduced acute insulin response (AIR) to an intravenous
      glucose bolus (adjusted P=0.045 and 0.035, respectively). SIRT1 expression in
      adipose biopsies was negatively correlated with BMI (adjusted P=0.00001). We
      conclude that variation in SIRT1 is nominally associated with reduced AIR and
      increased risk for type 2 diabetes. SIRT1 expression in adipose is correlated
      with BMI, but it remains unknown whether this is a cause or consequence of
      obesity.

PMID- 21871828
TI  - The G46S-hPAH mutant protein: a model to study the rescue of aggregation-prone
      PKU mutations by chaperones.
AB  - Phenylketonuria (PKU), the most common inborn error of metabolism, is caused by
      dysfunction of the liver enzyme phenylalanine hydroxylase (PAH), with more than
      550 PAH gene mutations identified to date. A large number of these mutations
      result in mutant forms of the enzyme displaying reduced stability, increased
      propensity to aggregate, and accelerated in cellulo degradation. Loss or
      reduction of human PAH activity results in hyperphenylalaninemia (HPA) which, if
      untreated, results in severe mental retardation and impaired cognitive
      development. Until now, strict low phenylalanine diet has been the most effective
      therapy, but as a protein misfolding disease PKU is a good candidate for
      treatment by natural/chemical/pharmacological chaperones. The natural cofactor of
      human PAH, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)), has already been
      approved for oral treatment of HPA, giving a positive response in mild forms of
      the disease showing considerable residual enzymatic activity. In the case of the
      most severe forms of PKU, ongoing studies with chemical and pharmacological
      chaperones to rescue misfolded mutant proteins from aggregation and degradation
      are providing promising results. The PKU mutation G46S is associated with a
      severe form of the disease, resulting in an aggregation-prone protein. The human
      PAH mutant G46S is rapidly degraded in the cellular environment and, in vitro
      (upon removal of its stabilizing fusion partner maltose binding protein (MBP))
      self-associates to form higher-order oligomers/fibrils. Here, we present an in
      vitro experimental model system to study the modulation of G46S aggregation by
      chemical/pharmacological chaperones, which may represent a useful approach to
      study the rescue of other severe PKU mutations by chemical/pharmacological
      chaperones.

PMID- 21871829
TI  - Phenylalanine hydroxylase deficiency: molecular epidemiology and predictable BH4
      responsiveness in South Portugal PKU patients.
AB  - Hyperphenylalaninemia (HPA, OMIM #261600), which includes phenylketonuria (PKU),
      is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH),
      being already described more than 600 different mutations. Genotype-phenotype
      correlation is a useful tool to predict the metabolic phenotype, to establish the
      better tailored diet and, more recently, to assess the potential responsiveness
      to BH(4) therapy, a current theme on PKU field. The aim of this study was the
      molecular analysis of the PAH gene, evaluation of genotype-phenotype
      relationships and prediction of BH(4)-responsiveness in the HPA population living
      in South Portugal. We performed the molecular characterization of 83 HPA patients
      using genomic DNA extracted from peripheral blood samples or Guthrie cards. PAH
      mutations were scanned by PCR amplification of exons and related intronic
      boundaries, followed by direct sequence analysis. Intragenic polymorphisms were
      determined by PCR-RFLP analysis. The results allowed the full characterization of
      67 patients. The mutational spectrum encompasses 34 distinct mutations, being the
      most frequent IVS10nt-11G>A (14.6%), V388M (10.8%), R261Q (8.2%) and R270K
      (7.6%), which account for 46% of all mutant alleles. Moreover, 12 different
      haplotypes were identified and most mutations were associated with a single one.
      Notably, more than half of the 34 mutations belong to the group of more than 70
      mutations already identified in BH(4)-responsive patients, according to BIOPKU
      database. Fifty one different genotypic combinations were found, most of them in
      single patients and involving a BH(4)-responsive mutation. In conclusion, a
      significant number (30-35%) of South Portugal PKU patients may potentially
      benefit from BH(4) therapy which, combined with a less strict diet, or eventually
      in special cases as monotherapy, may contribute to reduce nutritional
      deficiencies and minimize neurological and psychological dysfunctions.

PMID- 21871830
TI  - [Atrial fibrillation ablation: application of nurse methodology].
AB  - Ablation of pulmonary veins for treatment of atrial fibrillation involves
      applying radiofrequency energy wave by a catheter that causes a circumferential
      lesion to achieve electrical isolation and voltage drop in the interior. It is
      mainly applied when there is resistance to treatment and recurrence of symptoms
      affecting the quality of life of patients. The nurse is an important part of the
      multidisciplinary team who care for patients who undergo this procedure. The
      provision of comprehensive nursing care should include nursing procedures prior
      to, during, and after treatment to ensure the careful and systematic quality
      required. The aims of this article are: to provide specialised knowledge on the
      procedure of atrial fibrillation ablation, to describe the preparation of the
      electrophysiology laboratory, analyse nursing care and develop a standardized
      care plan for patients on whom this procedure is performed using the NANDA (North
      American Nursing Association) taxonomy and NIC (Nursing Intervention
      Classification).

PMID- 21871831
TI  - Beyond glucose lowering: glucagon-like peptide-1 receptor agonists, body weight
      and the cardiovascular system.
AB  - AIM: Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family: in
      the presence of elevated blood glucose, it stimulates insulin secretion and
      inhibits glucagon production. In addition, GLP-1 slows gastric emptying. GLP-1
      secretion has also been reported to potentially affect patients with type 2
      diabetes (T2DM) compared with non-diabetics and, as enzymatic inactivation by
      dipeptidyl peptidase-4 (DPP-4) shortens the GLP-1 half-life to a few minutes, GLP
      1 receptor agonists such as exenatide twice daily (BID) and liraglutide have been
      developed, and have become part of the management of patients with T2DM. This
      review focuses on the potential beneficial effects of these compounds beyond
      those associated with improvements in blood glucose control and weight loss,
      including changes in the cardiovascular and central nervous systems. METHODS:
      This was a state-of-the-art review of the literature to evaluate the
      relationships between GLP-1, GLP-1 receptor agonists, weight and the
      cardiovascular system. RESULTS: GLP-1 receptor agonists improve glucose control
      and do not significantly increase the risk of hypoglycaemia. Also, this new class
      of antidiabetic drugs was shown to favour weight loss. Mechanisms may involve
      central action, direct action by reduction of food intake and probably indirect
      action through slowing of gastric emptying. The relative importance of each
      activity remains unclear. Weight loss may improve cardiovascular outcomes in
      patients with T2DM, although GLP-1 receptor agonists may have other direct and
      indirect effects on the cardiovascular system. Reductions in myocardial infarct
      size and improvements in cardiac function have been seen in animal models.
      Beneficial changes in cardiac function were also demonstrated in patients with
      myocardial infarcts or heart failure. Indirect effects could involve a reduction
      in blood pressure and potential effects on oxidation. However, the mechanisms
      involved in the pleiotropic effects of GLP-1 receptor agonists have yet to be
      completely elucidated and require further study. CONCLUSION: These compounds may
      play an important role in the treatment of patients with T2DM as their potential
      effects go beyond glucose-lowering (weight loss, potential improvement of
      cardiovascular risk factors). However, to better understand their place in the
      management of T2DM, further experimental and clinical prospective studies are
      required.

PMID- 21871832
TI  - [Assisted Reproductive Technologies in HIV patients: a comprehensive review of
      indications, techniques and results].
AB  - Assisted Reproductive Technologies (ART) are authorized in France in couples
      infected by the human immunodeficiency virus (HIV) since the French legislation
      of May 10th, 2001. The goals are to reduce the risk of viral transmission between
      partners and to treat an underlying infertility. The classical techniques are
      used: IUI, IVF or ICSI, but all of them must be done in specifically authorized
      laboratories. ART outcome is favourable when only the man is infected, but seems
      to be less favourable when the woman is infected. Management of pregnancy
      planning should first propose to women infected by HIV, self inseminations when
      possible, and if needed, a quick ART treatment as some studies showed ovarian
      function alterations in HIV women. When the man is infected, IUI would be first
      proposed. Thousands of HIV positive male partners have used ART in Europe and no
      contamination has been reported so far. Approximately half of couples with one or
      both partners infected can hope to have a child through the ART process.

PMID- 21871833
TI  - [Robot-assisted laparoscopy in the management of recurrent pelvic cancer].
AB  - OBJECTIVES: The aim of this study is to establish the feasibility of the
      management of recurrent pelvic cancers by robot-assisted laparoscopy, and
      particularly the feasibility of robot-assisted laparoscopy anterior pelvic
      exenteration, from a single center series of seven patients. PATIENTS AND
      METHODS: From February 2007 to April 2010, all patients cared for recurrent
      pelvic cancer have been included (n=7). Five patients have been cared for a
      cervical cancer recurrence, one patient for recurrent VAIN 3, and one patient for
      squamous cell carcinoma of the vaginal vault after hysterectomy for cervical
      carcinoma in situ. All patients were benefited from robot-assisted laparoscopy:
      two had surgery such as anterior pelvic exenteration with Miami Pouch urinary
      reconstruction, and five had colpectomy with or without lymph node removal,
      including one with vaginal preparation first before vaginal cuff resection. Data
      were collected prospectively identifying treatment history, intraoperative data,
      immediate outcomes, pathological findings, and long-term outcomes. RESULTS: From
      February 2007 to April 2010, 195 patients underwent robot-assisted laparoscopy at
      the Institut Paoli-Calmettes. Among them, seven patients had pelvic cancer
      recurrence. The median age was 53 years (44 to 67). The median BMI was 25 (19.7
      to 35.3). The median Karnofsky index was 100 (80-100). The median operative time
      was 210 min (90 to 300) for colpectomy, 480 min for pelvectomy, 240 min (90-480)
      for the serie. The mean duration of the installation of the robot, all procedures
      combined, is estimated at 22.5 min (+/-4.8 min). There was no conversion to
      laparotomy, the median blood loss was 340 ml (100 to 800). One patient was
      transfused with two red blood cells. There was a surgical complication (wound of
      the inferior mesenteric artery). There were no early postoperative complications
      and the median hospital stay was 6 days (3-24). There was a late postoperative
      complication: a patient who underwent anterior pelvic exenteration had impaired
      wound healing, with scarring requiring led by the VAC system. On pathological
      findings, the average number of nodes removed in the pelvic was 8.5 (+/-2) on the
      left, and 4 (+/-1.4) on the right. Three patients had involved margins; it was an
      anterior pelvic exenteration and two colpectomy. There was no hospital mortality,
      neither post-operative mortality at D30 and D90. After a median follow up of 22
      months (9-34), the recurrence rate was 71% (5 patients out of 7), and one patient
      died 10 months after the intervention of a pulmonary embolism. DISCUSSION AND
      CONCLUSION: The surgical management of recurrent cervical cancer by laparoscopy
      assisted robot is feasible for selected indications, and could be proposed as an
      alternative to laparotomy. Monitoring data in this series raise the question of
      the validity of conservative treatment in cases of recurrent pelvic cancer. The
      possibilities in terms of urinary and vaginal reconstruction remain to be
      defined. The impact of this surgical approach on oncological data must be
      confirmed.

PMID- 21871834
TI  - The role of blood flow distribution in the regulation of cerebral oxygen
      availability in fetal growth restriction.
AB  - Fetal growth restriction (FGR) elicits hemodynamic compensatory mechanisms in the
      fetal circulation. These mechanisms are complex and their effect on the cerebral
      oxygen availability is not fully understood. To quantify the contribution of each
      compensatory mechanism to the fetal cerebral oxygen availability, a mathematical
      model of the fetal circulation was developed. The model was based on cardiac
      output distribution in the fetal circulation. The compensatory mechanisms of FGR
      were simulated and their effects on cerebral oxygen availability were analyzed.
      The mathematical analysis included the effects of cerebral vasodilation,
      placental resistance to blood flow, degree of blood shunting by the ductus
      venosus and the effect of maternal-originated placental insufficiency. The model
      indicated a unimodal dependency between placental blood flow and cerebral oxygen
      availability. Optimal cerebral oxygen availability was achieved when the
      placental blood flow was mildly reduced compared to the normal flow. This optimal
      ratio was found to increase as the hypoxic state of FGR worsens. The model
      indicated that cerebral oxygen availability is increasingly dependent on the
      cardiac output distribution as the fetus gains weight.

PMID- 21871835
TI  - Do sphenoidal electrodes aid in surgical decision making in drug resistant
      temporal lobe epilepsy?
AB  - OBJECTIVE: The utility of sphenoidal electrodes (SPh) in analyzing interictal
      epileptiform discharges (IEDs) and ictal electrography remains controversial,
      despite its widespread use. METHODS: One hundred and twenty-two consecutive
      patients with presumed temporal lobe epilepsy (TLE) who underwent presurgical
      evaluation were prospectively studied. SPh and Silverman's electrodes were
      placed, in addition to routine electrodes in 10-20 international system. IEDs and
      ictal electroencephalography (EEG) were analyzed separately in bipolar and
      referential montages. The proportion of patients selected for surgery after
      adjusting for SPh placement based on the earlier ictal onset and IEDs were
      analyzed. RESULTS: Of the 8701 IEDs in SPh, only 65% were seen over the scalp
      bipolar montage; 1392 (16%) IEDs were confined to SPh electrodes, and were not
      seen at scalp bipolar montage (p<0.001). Spike amplitudes were highest at SPh
      (p<0.001). Of the 592 seizures analyzed, 62 (61%) had simultaneous SPh and scalp
      onset, while in 26 (25%) SPh onset preceded the scalp. CONCLUSIONS: Out of the 35
      patients with unilateral mesial temporal sclerosis (MTS) with additional
      neocortical changes and/or non-lateralized bitemporal IEDs and/or diffuse ictal
      onset (group 1), 27 were selected for surgery (77%). About 7% was selected for
      surgery in this group by SPh placement. Also, in patients with bilateral MTS
      (group 2), 25% (5/20) were chosen for anterior temporal lobectomy, SPh provided
      an additional benefit in 11% (p<0.001). Patients with normal magnetic resonance
      imaging (group 3) and temporal plus epilepsy (group 4) had a lower surgical
      yield, only 12% and 9.5% could undergo surgery. They were denied surgical
      candidacy with SPh (p<0.001). SIGNIFICANCE: One-third of patients after SPh
      placement were selected for resective surgery obviating the need for invasive
      monitoring. The maximum yield was noted in unilateral MTS (associated with
      additional neocortical features or non-lateralized bilateral temporal interictal
      IEDs or diffuse ictal onset in scalp EEG) and in bilateral MTS. Those with normal
      MRI/temporal plus epilepsy could be excluded from direct resective surgery.

PMID- 21871836
TI  - The association between obstructive sleep apnea and dietary choices among obese
      individuals during middle to late childhood.
AB  - OBJECTIVE: Determine whether obstructive sleep apnea (OSA) is associated with the
      dietary choices of obese individuals during middle- to late-childhood. It was
      hypothesized that OSA would be associated with increased caloric content of a
      dinner order, particularly with high carbohydrate food choices. Secondarily, we
      examined the relationships between sleep duration and dietary choices. METHODS:
      42 obese subjects aged 10-16.9 years participated in a cross-sectional study that
      involved systematic collection of sleep duration (based on actigraphy), presence
      and severity of obstructive sleep apnea (obstructive apnea+hypopnea index [AHI]
      from inpatient polysomnography) and the macronutrient content of dinners ordered
      from a standardized hospital menu the evening before the polysomnogram. RESULTS:
      Primary analyses using Spearman rank-order correlations found that AHI was
      significantly associated with total calories, as well as grams of fat and
      carbohydrate, but not protein. These macronutrient variables did not correlate
      with sleep duration across a week, nor the night before the meal. Findings were
      unchanged after correcting for age- and sex-adjusted BMI. CONCLUSIONS: More
      severe OSA appears to be associated with an increased preference for calorie
      dense foods that are high in fat and carbohydrates in a manner that is
      independent of degree of obesity. Although this novel finding awaits replication,
      it has potential implications for the clinical care of obese youth and
      individuals with OSA, adds to the limited data that relate sleep to dietary
      choices and may have implications for OSA-related morbidity.

PMID- 21871837
TI  - Autologous transplant in the treatment of severe aplastic anemia--a case report.
AB  - The initial use of immunosuppressive therapy (IST) in severe aplastic anemia
      (sAA) or reapplication of IST-centered methods following disease relapse is
      successful only in well-selected patients. The potential treatment by autologous
      stem cell (SC) transplant in sAA is still an innovative/pioneering therapeutic
      approach. To our best knowledge, this is the second published case of autologous
      SC transplant in sAA. The aim of this work was to optimize mobilization and
      timing for SC harvesting - using our own controlled-rate cryopreservation - with
      higher CD34(+)/CD90(+) subset yield and recovery in order to obtain complete and
      long-term hematopoietic reconstitution following autologous SC transplant. We
      report a 35 year-old sAA male patient who initially underwent IST using rabbit
      ATG and Cyclosporine A (CsA). He was supportive transfusion dependent for the
      whole period of IST-phase. After the second IST-cycle, polymorphonuclear (PMN)
      cell count increase (>2.0 * 10(9)/L) was observed, when SC mobilization, two
      large volume leukapheresis procedures and following autologous transplant were
      performed. The yields of harvested CD34(+) and CD34(+)/CD90(+) cells were 5.75 *
      10(6)/kgbm and 1.7 * 10(6)/kgbm, respectively. The quantity of applied CD34(+)
      and CD34(+)/CD90(+) cells in autologous SC transplant were 5.45 * 10(6)/kgbm (7
      AAD(CD34)(+)(viability)=95.42%) and 1.63 * 10(6)/kgbm (7
      AAD(CD34)(+)(/CD90)(+)(viability)=95.42%), respectively. Hematopoietic
      reconstitution registered due to second month after autologous SC transplant and
      he is 24 months in complete medullar, hematological and clinical remission, with
      normal cytogenetic status - applying only continuous CsA therapy. The results
      obtained strongly confirm that in sAA, with no allogeneic SC donor, autologous
      transplant can result in a successful clinical outcome. We suggest that
      CD34(+)/CD90(+) subset count in peripheral blood and/or cell-harvest could be
      more valuable predictive factor than total CD34(+) quantity of optimized
      collection-timing and superior treatment efficacy of autologous SC transplant in
      sAA.

PMID- 21871838
TI  - Quality of life and related factors in adult patients with epilepsy in China.
AB  - OBJECTIVE: The objective of this work was to study the quality of life (QOL) of
      adult patients with epilepsy in northern China. METHODS: Three hundred three
      adult patients with epilepsy were identified using a strict procedure of
      diagnosis at the outpatient clinic of the epilepsy center, and then their QOL was
      evaluated with the Chinese version of the Quality of Life in Epilepsy Inventory
      89. RESULTS: QOLIE-89 total score and many of the subscale scores were decreased.
      The greatest decreases were observed in the Seizure Worry and Medication Effects
      subscale scores. QOLIE-89 total scores of married patients (57.1+/-15.3) were
      lower than those of unmarried patients (70.9+/-15.7) (P<0.001). Correlation
      analysis revealed that QOLIE-89 total score was negatively correlated with age,
      course of disease, seizure severity, antiepileptic drug, type of seizure, and
      seizure frequency (r=-0.334, -0.281, -0.424, -0.117, -0.145, and -0.274
      respectively, P<0.01), and was positively correlated with educational level and
      economic status (r=0.245 and 0.328 respectively, P<0.01). Multiregression
      analysis revealed that five factors entered the regression equation: age (beta=
      0.545, P=0.001), course of disease (beta=-0.311, P=0.001), seizure severity
      (beta=-10.014, P=0.001), educational level (beta=3.274, P=0.002), and economic
      status (beta=6.431, P=0.001). CONCLUSION: Quality of life of adult patients with
      epilepsy decreases with older age, more difficult course of disease, and higher
      seizure frequency. Higher educational level and economic status are protective
      factors in the QOL of adult patients.

PMID- 21871839
TI  - Teaching diagnostic approach to a patient through cinema.
AB  - Films are produced with the aim of entertaining people, but recently there has
      been increasing use of films to educate medical trainees about various disorders,
      symptoms of these disorders, patient-therapist interactions, and various other
      medical and psychiatric issues. Discussions in academic circles have moved from
      criticism of negative portrayals of mental illness in earlier films to their use
      in teaching sessions. Films can be used either in full length or clip format to
      conduct training modules. Use of the film Stigmata to train residents about
      diagnostic dilemmas and taking a diagnostic approach to patients is discussed.

PMID- 21871840
TI  - The status of low vision rehabilitation and certification in the state of
      Michigan.
AB  - BACKGROUND: With the estimated increase in the number of Americans with vision
      related disabilities on the horizon, the need for optometrists with expertise in
      low vision rehabilitation services will increase. State optometric certification
      in low vision rehabilitation is currently only available in 3 states through
      affiliations between the state optometric associations and other organizations or
      government entities. METHODS: A mail survey was conducted among Michigan
      Optometric Association member optometrists designed to address the current
      percentage of optometrists who practice low vision rehabilitation as well as the
      percentage who are low vision certified through the Michigan Optometric
      Association and to establish future need for additional low vision rehabilitation
      providers in the state. RESULTS: Of the 188 participants, only 26.0% stated that
      they provide low vision rehabilitation services, the majority of whom provide
      only primary care low vision rehabilitation. Only 6.4% of respondents are
      certified low vision rehabilitation specialists through the Michigan Optometric
      Association. CONCLUSION: The low percentage of optometrists in the state of
      Michigan who practice low vision rehabilitation may lead to a shortage of
      providers for the aging and visually impaired Michigan population seeking low
      vision rehabilitation services. Even fewer are certified low vision providers
      through the voluntary Michigan Optometric Association certification process.

PMID- 21871841
TI  - Dynamic regulation of Emi2 by Emi2-bound Cdk1/Plk1/CK1 and PP2A-B56 in meiotic
      arrest of Xenopus eggs.
AB  - In vertebrates, unfertilized eggs are arrested at metaphase of meiosis II by Mos
      and Emi2, an inhibitor of the APC/C ubiquitin ligase. In Xenopus, Cdk1
      phosphorylates Emi2 and both destabilizes and inactivates it, whereas Mos
      recruits PP2A phosphatase to antagonize the Cdk1 phosphorylation. However, how
      Cdk1 phosphorylation inhibits Emi2 is largely unknown. Here we show that multiple
      N-terminal Cdk1 phosphorylation motifs bind cyclin B1-Cdk1 itself, Plk1, and
      CK1delta/epsilon to inhibit Emi2. Plk1, after rebinding to other sites by self
      priming phosphorylation, partially destabilizes Emi2. Cdk1 and CK1delta/epsilon
      sequentially phosphorylate the C-terminal APC/C-docking site, thereby
      cooperatively inhibiting Emi2 from binding the APC/C. In the presence of Mos,
      however, PP2A-B56beta/epsilon bind to Emi2 and keep dephosphorylating it,
      particularly at the APC/C-docking site. Thus, Emi2 stability and activity are
      dynamically regulated by Emi2-bound multiple kinases and PP2A phosphatase. Our
      data also suggest a general role for Cdk1 substrate phosphorylation motifs in M
      phase regulation.

PMID- 21871842
TI  - A wt1-controlled chromatin switching mechanism underpins tissue-specific wnt4
      activation and repression.
AB  - Wt1 regulates the epithelial-mesenchymal transition (EMT) in the epicardium and
      the reverse process (MET) in kidney mesenchyme. The mechanisms underlying these
      reciprocal functions are unknown. Here, we show in both embryos and cultured
      cells that Wt1 regulates Wnt4 expression dichotomously. In kidney cells, Wt1
      recruits Cbp and p300 as coactivators; in epicardial cells it enlists Basp1 as a
      corepressor. Surprisingly, in both tissues, Wt1 loss reciprocally switches the
      chromatin architecture of the entire Ctcf-bounded Wnt4 locus, but not the
      flanking regions; we term this mode of action "chromatin flip-flop." Ctcf and
      cohesin are dispensable for Wt1-mediated chromatin flip-flop but essential for
      maintaining the insulating boundaries. This work demonstrates that a
      developmental regulator coordinates chromatin boundaries with the transcriptional
      competence of the flanked region. These findings also have implications for
      hierarchical transcriptional regulation in development and disease.

PMID- 21871843
TI  - Role of neuron density of the stellate ganglion on regulation of the basilar
      artery volume in subarachnoid hemorrhage: An experimental study.
AB  - BACKGROUND: The role of neuron density (of the stellate ganglion) in basilar
      artery vasospasm after subarachnoid hemorrhage (SAH) has not previously been
      investigated. This subject was studied. METHODS: This study was conducted on 24
      rabbits. Four of them were used as the baseline control group. Experimental SAH
      was applied to the 15 animals; the remaining five of them were used as a sham
      group injecting by the serum physiologic saline (PS) and followed up twenty days
      later. Stellate ganglion neuron densities were estimated stereologically.
      Vasospasm index (VSI) was used to assess the severity of vasospasm. The value of
      VSI between 1 and 1.5 was accepted as no vasospasm, 1.5-2 was accepted as light
      vasospasm and 2 or greater than 2 was accepted as severe vasospasm. Results were
      compared statistically. RESULTS: The mean basilar artery VSI in the control group
      (n: 4) was calculated as 1.24+/-0.39 and the neuron density of stellate ganglion
      was calculated as 8320+/-675/mm(3). These values in the PS group (n: 5) were
      calculated as 1.26+/-0.37 and 8380+/-680/mm(3). In animals with light basilar
      artery vasospasm (n: 6), the basilar artery VSI and neuron density of stellate
      ganglion were 1.65+/-0.37, 9210+/-460/mm(3) consecutively, but the basilar artery
      VSI was 2.07+/-0.40 and neuron density was 12,075+/-950/mm(3) in animals with
      severe vasospasm (n: 9). CONCLUSION: The neuron density of stellate ganglion may
      play an important role in the development of basilar artery vasospasm. The
      beneficial effect of sympathectomy for the prevention of cerebral vasospasm may
      be explained through this mechanism.

PMID- 21871844
TI  - Circadian rhythm of rest activity and autonomic nervous system activity at
      different stages in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) often suffer from non-motor symptoms,
      including sleep and autonomic dysfunctions, controlled by circadian regulation.
      To evaluate the alteration of circadian rhythm in PD patients, we investigated
      both rest activities and autonomic functions. Twenty-seven patients with
      idiopathic PD and 30 age-matched control subjects were recruited. Group
      comparisons of controls (mean age: 68.93 years), early-PD patients classified as
      Hoehn-Yahr (HY) stage 1&2 (mean age: 70.78 years), and advanced-PD as HY 3&4
      (mean age: 68.61 years) were conducted. Measurement of rest activities was
      performed using Actigraph for 7 continuous days, and included measuring rhythm
      patterns (activity patterns recorded in or out of bed) and circadian rhythm
      amplitudes (power of the cycle being closest to 24h). A power spectral analysis
      of heart rate variability (HRV) using 24-hour ambulatory ECG was also performed.
      The actigraphic measurements indicated that statistically PD patients have lower
      activity levels when out of bed and higher activity levels when in bed, and that,
      the circadian rest-activity rhythm in PD decreases with disease severity. The HRV
      analysis showed that the total frequency component and low frequency/high
      frequency ratio were low in PD patients, suggesting that autonomic activities and
      the circadian rhythm of the sympathetic nervous system are attenuated in PD. This
      study elucidated the disorganization in the rest activities and HRV of PD
      patients as well as the gradual alterations in the circadian rhythm. The
      circadian rhythm disturbances are important to consider the mechanism of non
      motor symptoms that occur from early stage of PD.

PMID- 21871845
TI  - A highly sensitive LC-ESI-MS/MS method for the quantification of cholesterol
      ozonolysis products secosterol-A and secosterol-B after derivatization with 2
      hydrazino-1-methylpyridine.
AB  - Cholesterol ozonolysis products, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al
      (secosterol-A) and its aldolization product 3beta-hydroxy-5beta-hydroxy-B
      norcholestane-6beta-carboxaldehyde (secosterol-B) have been found in
      atherosclerosis plaques and the brain tissues of Alzheimer's disease patients,
      implicating them in the pathogenesis of cardiovascular and neurodegenerative
      diseases. We have recently reported that when cholesterol is oxidized with an
      ozone-like oxidant generated by activated mouse neutrophils, secosterol-A is
      generated which is then converted to secosterol-B by an aldol reaction. To
      investigate further pathophysiological roles of secosterols, we have developed a
      highly sensitive method to detect secosterol-A and -B as derivatives with 2
      hydrazino-1-methylpyridine (HMP) by LC-ESI-MS/MS. The limits of detection for the
      HMP derivatives of secosterol-A and secosterol-B were 0.05 and 0.01fmol,
      respectively, which were approximately 400 and 2000 times better than those for
      underivatized secosterol-A and -B. We also developed a highly reproducible and
      accurate method to extract, purify and derivatize secosterol in small volumes of
      biological specimens. Using this method, we determined the levels of secosterol-A
      and -B as 1.4 +/- 0.7 and 4.3 +/- 0.8 nM, respectively, in the plasma of normal
      C57BL/6 mice, and in the range of 10.4 +/- 16.3 to 40.7 +/- 20.1 pmol/g and 110.9
      +/- 10.6 to 161.5 +/- 56.3 pmol/g, respectively, in the brain, liver and lung
      tissues.

PMID- 21871846
TI  - Revisited mycolic acid pattern of Mycobacterium confluentis using thin-layer
      chromatography.
AB  - The profile of mycolic acids from Mycobacterium confluentis has not been
      adequately published. However, the definition of the composition of mycolic acids
      is a critical element for describing new mycobacterial species. Thus, an
      erroneously published profile can lead to confusing citations. The aim of this
      article is to make the protocols clear, by using thin layer chromatography as a
      tool, for defining the discrete pattern of mycolic acids of any newly reported
      mycobacterial species. By using this method, and corroborated using nuclear
      magnetic resonance analysis, we demonstrated that M. confluentis contains alpha
      mycolates (type I) and epoxymycolates (type V mycolic acids).

PMID- 21871847
TI  - Comparison of molecular dynamics simulation methods for amyloid beta(1-42)
      monomers containing D-aspartic acid residues for predicting retention times in
      chromatography.
AB  - Molecular dynamics simulations of amyloid beta(1-42) containing D-aspartic acid
      residues were performed using several continuous solvent models to investigate
      the usefulness of simulation methods for D-amino acid-containing proteins and
      peptides. Normal molecular dynamics simulations and replica exchange molecular
      dynamics simulations, which are one of the generalized-ensemble algorithms, were
      performed. Because the beta-structure contents of amyloid beta(1-42) peptides
      obtained by replica exchange molecular dynamics simulations with Onufriev
      Bashford-Case generalized Born implicit solvent were qualitatively consistent
      with experimental data, replica exchange molecular dynamics rather than other
      methods appeared to be more reasonable for calculations of amyloid beta(1-42)
      containing D-aspartic acid residues. Computational results revealed that peptides
      with stereoinversion of Asp23 tend to form beta-sheet structures by themselves,
      in contrast to the wild-type peptides that form beta-sheet structures only after
      aggregation. These results are expected to be useful for computational
      investigations of proteins and peptides such as prediction of retention time of
      peptides and proteins containing D-aspartic acid residues.

PMID- 21871848
TI  - The determination of ascorbic acid and uric acid in human seminal plasma using an
      HPLC with UV detection.
AB  - Oxidative stress has been proposed as one of the potential causes for infertility
      in men. Ascorbic acid and uric acid play important role in protection of
      spermatozoa against free radicals. A method for the simultaneous determination of
      ascorbic acid and uric acid in human seminal plasma using HPLC with UV detection
      and investigation their clinical significance as antioxidants protecting male
      germ cells against oxidative damage are described. Semen samples were obtained
      from consecutive male partners of couples presenting for a fertility evaluation.
      After liquefaction, the samples were centrifuged and the supernatants were
      diluted with dithiothreitol solution and after a filtration injected onto an
      analytical column. For the separation, a reverse-phase column MAG 1, 250 mm * 4.6
      mm, Labiospher PSI 100 C18, 5 MUm, was used. The mixture of ethanol and 25 mmol/L
      sodium dihydrogenphosphate (2.5:97.5, v/v), pH 4.70 was used as a mobile phase.
      Analytical performance of this method is satisfactory for both ascorbic acid and
      uric acid: the intra-assay and inter-assay coefficients of variation were below
      10%. Quantitative recoveries from spiked seminal plasma were between 92.1 and
      102.1%. We have found no significant differences in both ascorbic acid and uric
      acid concentration between the smokers and non-smokers (351.0 +/- 237.9 MUmol/L
      and 323.7 +/- 99.5 MUmol/L vs. 444.8 +/- 245.5 MUmol/L and 316.6 +/- 108.9
      MUmol/L, p>0.05). This assay is a simple and reproducible HPLC method for the
      simultaneous measurement of ascorbic acid and uric acid in human seminal plasma.

PMID- 21871849
TI  - [Relationship between PAO2/FIO2 and SATO2/FIO2 with mortality and duration of
      admission in critically ill children].
AB  - OBJECTIVES: The aim of this study is to analyse the relationships and the
      association between PaO(2)/FiO(2) and SatO(2)/FiO(2with) the duration of
      admission in Paediatric Intensive Care Units (PICU) and mortality, and to study
      the relationships between both ratios. MATERIAL AND METHODS: A retrospective
      study was conducted on PICU patients in whom a gas analysis was performed in the
      first twenty-four hours of admission. Demographic, clinical and ventilation
      variables were collected, and the relationship between PaO(2)/FiO(2) and
      SatO(2)/FiO(2) with days of admission and mortality was determined. Finally, the
      best cut-off points of SatO(2)/FiO(2) were determined for PaO(2)/FiO(2) values
      greater and less than 200. RESULTS: Of 512 patients admitted during one year, a
      gas analysis was performed on 358, 65% of those in arterial blood. The median
      duration of hospitalization was two days and there were 11 patient deaths. There
      was a low negative correlation between the values of PaO(2)/FiO(2) and
      SatO(2/)FiO(2) on admission to PICU and with duration of admission, and an
      inverse association with mortality (P<.01). This association was stronger for the
      PaO(2)/FiO(2) ratio in patients with heart disease, those undergoing invasive
      mechanical ventilation, and for arterial blood samples. PaO(2)/FiO(2) and
      SatO(2)/FiO(2) ratios were significantly correlated with each other. A cut-off of
      200 for SatO(2)/FiO(2) had a sensitivity of 97.5% for classifying patients with
      PaO(2)/FiO(2) values lower or higher than 200. CONCLUSIONS: PaO(2)/FiO(2) and
      SatO(2)/FiO(2) index are markers of severity in critically ill patients. In
      patients who do not have an arterial line, SatO(2)/FiO(2) index can be used for
      assessment of oxygenation as an indicator of severity in children in critical
      condition.

PMID- 21871850
TI  - The harmful and beneficial impacts of weight bias on well-being: the moderating
      influence of weight status.
AB  - Weight bias is evident among normal weight and obese individuals. This weight
      bias may be associated with comparisons to others, which may enhance feelings of
      self-worth. However, the ego-enhancing versus ego-diminishing influence of these
      evaluations may be moderated by the individual's weight status, and the strength
      of these effects may be moderated by gender. Eight-five participants completed
      the Implicit Associations Test, questionnaires assessing explicit weight bias,
      body image, and self-esteem, and height and weight assessments. Implicit weight
      bias was prevalent among all individuals, p<.001, and was associated with a more
      positive body image, ps<.05, and higher self-esteem, ps<.01, for thinner
      individuals but a more negative body image and lower self-esteem for heavier
      individuals. Gender moderation effects were not observed. It is arguably
      problematic that the positive benefits to normal weight individuals' self-esteem
      and body image appear to come via negative comparisons with overweight
      individuals.

PMID- 21871851
TI  - The recombination landscape around forensic STRs: Accurate measurement of genetic
      distances between syntenic STR pairs using HapMap high density SNP data.
AB  - Family studies can be used to measure the genetic distance between same
      chromosome (syntenic) STRs in order to detect physical linkage or linkage
      disequilibrium. However, family studies are expensive and time consuming, in many
      cases uninformative, and lack a reliable means to infer the phase of the
      diplotypes obtained. HapMap provides a more comprehensive and fine-scale
      estimation of recombination rates using high density multi-point SNP data
      (average inter-SNP distance: 900 nucleotides). Data at this fine scale detects
      sub-kilobase genetic distances across the whole recombining human genome. We have
      used the most recent HapMap SNP data release 22 to measure and compare genetic
      distances, and by inference fine-scale recombination rates, between 29 syntenic
      STR pairs identified from 39 validated STRs currently available for forensic use.
      The 39 STRs comprise 23 core loci: SE33, Penta D & E, 13 CODIS and 7 non-CODIS
      European Standard Set STRs, plus supplementary STRs in the recently released
      Promega CS-7TM and Qiagen Investigator HDplexTM kits. Also included were D9S1120,
      a marker we developed for forensic use unique to chromosome 9, and the novel
      D6S1043 component STR of SinoFilerTM (Applied Biosystems). The data collated
      provides reliable estimates of recombination rates between each STR pair, that
      can then be placed into haplotype frequency calculators for short pedigrees with
      multiple meiotic inputs and which just requires the addition of allele
      frequencies. This allows all current STR sets or their combinations to be used in
      supplemented paternity analyses without the need for further adjustment for
      physical linkage. The detailed analysis of recombination rates made for autosomal
      forensic STRs was extended to the more than 50 X chromosome STRs established or
      in development for complex kinship analyses.

PMID- 21871852
TI  - Intraoperative events and their outcome: data from 4007 laparoscopic
      interventions by the French "Club Coelio".
AB  - AIM: To assess the operative and postoperative course of intraoperative events
      occurring in laparoscopic surgery according to the classification of Clavien.
      This evaluation aims at ascertaining morbidity and mortality of abdominal
      laparoscopic operations, thus serving as a reference for future comparative
      studies. METHOD: Twenty-nine senior surgeons, all of them members of the Coelio
      Club prospectively and consecutively summarized all their laparoscopic activity
      over a period of 6 months. RESULTS: Of 4007 patients, 373 (9.31%) developed
      complications, 69 (1.72%) requiring surgery. Establishing the pneumoperitoneum
      and trocar placement caused 15 vascular (0.37%) and six visceral (0.15%)
      injuries; seven vascular (0.17%) and 22 visceral (0.55%) injuries occurred
      intraoperatively. Surgery of the colon and especially the rectum were associated
      with the highest morbidity with Clavien grades III, IV and V reported in 8, 10
      and 15.97% of patients, respectively; 1.2% occurred in biliary surgery and 0.67%
      in inguinal/femoral hernia repair. CONCLUSION: The prevalence of surgical
      intraoperative events and postoperative complications is higher than reported in
      the literature. Clavien's classification is applicable to abdominal laparoscopic
      surgery; further information is necessary to assess intraoperative surgical
      events as well as conversions.

PMID- 21871853
TI  - Toward a definition of intolerance of uncertainty: a review of factor analytical
      studies of the Intolerance of Uncertainty Scale.
AB  - Since its emergence in the early 1990s, a narrow but concentrated body of
      research has developed examining the role of intolerance of uncertainty (IU) in
      worry, and yet we still know little about its phenomenology. In an attempt to
      clarify our understanding of this construct, this paper traces the way in which
      our understanding and definition of IU have evolved throughout the literature.
      This paper also aims to further our understanding of IU by exploring the latent
      variables measures by the Intolerance of Uncertainty Scale (IUS; Freeston,
      Rheaume, Letarte, Dugas & Ladouceur, 1994). A review of the literature
      surrounding IU confirmed that the current definitions are categorical and lack
      specificity. A critical review of existing factor analytic studies was carried
      out in order to determine the underlying factors measured by the IUS. Systematic
      searches yielded 9 papers for review. Two factors with 12 consistent items
      emerged throughout the exploratory studies, and the stability of models
      containing these two factors was demonstrated in subsequent confirmatory studies.
      It is proposed that these factors represent (i) desire for predictability and an
      active engagement in seeking certainty, and (ii) paralysis of cognition and
      action in the face of uncertainty. It is suggested that these factors may
      represent approach and avoidance responses to uncertainty. Further research is
      required to confirm the construct validity of these factors and to determine the
      stability of this structure within clinical samples.

PMID- 21871854
TI  - The future role of the gastroenterologist in digestive oncology: an international
      perspective.

PMID- 21871855
TI  - Potassium values in cardiac arrest patients measured with a point-of-care blood
      gas analyzer.

PMID- 21871856
TI  - Increasing expression of (CCAAT enhancer binding protein) homologous protein
      induced by endoplasmic reticulum stress in myocardium after cardiac arrest and
      resuscitation in rat.
AB  - OBJECTIVES: Post-resuscitation myocardial dysfunction yields high rates of
      mortality, but its potential mechanism remains poorly understood. This study
      investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis is
      activated in the heart after cardiac arrest (CA) and resuscitation. METHODS:
      Wistar rats were subjected to 5 min electrically induced CA and then resuscitated
      by mechanical chest compression and epinephrine administration. Animals were
      decapitated at 3, 6, 12 and 24h (n=8, per group) after return of spontaneous
      circulation (ROSC). Myocardial specimens were analysed using electron microscopy,
      terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay,
      reverse transcription polymerase chain reaction, Western blotting and
      immunohistochemistry. RESULTS: The ER, mitochondria and nuclei in cardiomyocytes
      from the experimental groups were seriously damaged. Typical apoptotic nuclei
      were observed in cardiomyocytes 24h after resuscitation. TUNEL showed an
      approximately two-fold increase in the percentage of apoptotic cardiomyocytes 24h
      post-ROSC. The mRNA levels of glucose-regulated protein78 (GRP78) and
      calreticulin (CRT) were significantly elevated 3-24h after reperfusion. The
      transcription of the ER stress-associated apoptotic gene chop increased. The
      protein expressions of GRP78 and CRT were up-regulated at first; the C/EBP (CCAAT
      enhancer binding protein) homologous protein (CHOP) then increased, along with
      elevations in the active form of caspase-3. In situ immunostaining of ER stress
      markers also demonstrated that ER stress occurred in the myocardium after CA and
      resuscitation. CONCLUSION: ER stress and the CHOP apoptotic pathway are activated
      in the myocardium after CA and resuscitation. ER stress-mediated apoptosis may be
      one of the main pathological mechanisms of post-resuscitation myocardial injury.

PMID- 21871857
TI  - Pharmacokinetics of intraosseous and central venous drug delivery during
      cardiopulmonary resuscitation.
AB  - We compared the pharmacokinetics of intraosseous (IO) drug delivery via tibia or
      sternum, with central venous (CV) drug delivery during cardiopulmonary
      resuscitation (CPR). METHODS: CPR of anesthetized KCl arrest swine was initiated
      8 min post arrest. Evans blue and indocyanine green, each were simultaneously
      injected as a bolus with adrenaline through IO sternal and tibial needles,
      respectively, n=7. In second group (n=6) simultaneous IO sternal and IV central
      venous (CV) injections were made. RESULTS: Peak arterial blood concentrations
      were achieved faster for sternal IO vs. tibial IO administration (53+/-11 s vs.
      107+/-27 s, p=0.03). Tibial IO dose delivered was 65% of sternal administration
      (p=0.003). Time to peak blood concentration was similar for sternal IO and CV
      administration (97+/-17 s vs. 70+/-12 s, respectively; p=0.17) with total dose
      delivered of sternal being 86% of the dose delivered via CV (p=0.22).
      CONCLUSIONS: IO drug administrations via either the sternum or tibia were
      effective during CPR in anesthetized swine. However, IO drug administration via
      the sternum was significantly faster and delivered a larger dose.

PMID- 21871858
TI  - Simulation provides a window on the quality and safety of the system.

PMID- 21871859
TI  - Expansion of a medical emergency team system to a mental health facility.
AB  - BACKGROUND: Clinical emergency response systems such as medical emergency teams
      (MET) are used in many hospitals worldwide, but the effect that these systems
      have in mental health facilities is unknown. This study examined the rate and
      nature of MET calls to a mental health facility that had relocated to the campus
      of a tertiary referral hospital. METHODS: This study was a prospective,
      observational study of MET calls to a newly constructed 170 bed mental health
      facility. Data were collected on the number and nature of MET calls to the
      facility. RESULTS: Over 24 months, there were 66 MET calls to the mental health
      facility, and 1217 MET calls at the main hospital. The mean MET call rate was
      14.2 calls per 1000 admissions (95% confidence interval (CI) 10.8-17.7) at the
      mental health facility, and 14.7 calls per 1000 admissions (95% CI 13.9-15.5) at
      the main hospital. Neurological and cardiovascular problems were present in 61%
      and 41% of MET calls. CONCLUSION: The rate of MET calls to a new mental health
      facility can be similar to that of a tertiary hospital. Staff attending MET calls
      need to be prepared to manage predominantly neurological and cardiovascular
      problems.

PMID- 21871860
TI  - For whom the bell tolls....

PMID- 21871861
TI  - Ultrastructural evidence of mitochondrial abnormalities in postresuscitation
      myocardial dysfunction.
AB  - OBJECTIVES: Though there is evidence to implicate that the mitochondrion may play
      an important role in the development of postresuscitation myocardial dysfunction,
      limited data are available regarding the ultrastructural alterations of the
      mitochondria, mitochondrial energy-producing ability, and their relationship to
      postresuscitation myocardial dysfunction. This study was designed to determine
      whether mitochondrial abnormalities contribute to the development of
      postresuscitation myocardial dysfunction. METHODS: Fifteen anesthetized male
      Sprague-Dawley rats were randomized to: (1) global myocardial
      ischemia/reperfusion, in which 8 min of ventricular fibrillation was induced and
      successful defibrillation was achieved after 6 min of cardiopulmonary
      resuscitation (CPR); (2) global myocardial ischemia, in which ventricular
      fibrillation and CPR were performed without defibrillation attempt; and (3) sham
      control. RESULTS: Myocardial function was significantly impaired after
      resuscitation. Mitochondria were massively swollen in global ischemic hearts and
      mildly swollen in the resuscitated hearts. Concomitantly, ATP levels abruptly
      declined during global ischemia and partially recovered after resuscitation.
      Furthermore, mitochondrial abnormalities were supported by the incapability of
      utilizing energy substrates manifested by the accumulations of intramyocellular
      lipid droplets and glycogen deposits. CONCLUSIONS: In this model of cardiac
      arrest and CPR, the presence of ultrastructural mitochondrial abnormalities,
      further evidenced by the incapability of utilizing energy substrates and
      impairment of energy-production, might, in part, contribute to the development of
      postresuscitation myocardial dysfunction.

PMID- 21871862
TI  - The Saudi experience in fludarabine-based conditioning regimens in patients with
      Fanconi anemia undergoing stem cell transplantation: excellent outcome in
      recipients of matched related stem cells but not in recipients of unrelated cord
      blood stem cells.
AB  - Low-dose cyclophosphamide (CY) is now considered the backbone of many of the
      conditioning regimens used in patients with Fanconi anemia undergoing allogeneic
      stem cell transplantation (SCT). To reduce the risk of rejection and improve
      results, CY is usually used in combination with other agents/modalities, such as
      antithymocyte globulin (ATG), busulfan, radiation, and, more recently,
      fludarabine (Flu). In this study, we used a uniform Flu-based conditioning
      regimen (ie, CY, Flu, ATG) in 26 pediatric patients with Fanconi anemia
      undergoing SCT. The median patient age at the time of SCT was 7.8 years, and the
      stem cell source was an HLA-matched related donor in 19 patients and partially
      HLA-matched unrelated cord blood in 7 patients. The CY, Flu, ATG regimen was well
      tolerated overall, with a remarkably low incidence of graft-versus-host disease
      and hemorrhagic cystitis. All 19 patients in the matched related donor group
      engrafted and were alive and transfusion-independent at a median follow-up time
      of 19 months, compared with only 2 of 7 patients in the unrelated cord blood
      group. We conclude that the combination of CY, Flu, and ATG in the doses used in
      this study is well tolerated, and that the proclaimed positive effect of adding
      Flu to the conditioning regimens of patients with Fanconi anemia undergoing SCT
      is most pronounced in recipients of HLA-matched related transplants. Its value in
      unrelated cord blood transplantation probably depends on other factors, such as
      the degree of HLA matching and the cell dose.

PMID- 21871863
TI  - Host basophils are dispensable for induction of donor T helper 2 cell
      differentiation and severity of experimental graft-versus-host disease.
AB  - Host hematopoietic-derived antigen-presenting cells are important for induction
      of graft-versus-host disease (GVHD). The relative importance of various subsets
      of hematopoietic-derived antigen-presenting cells is not well understood. Recent
      data suggest that basophils can function as antigen-presenting cells and induce T
      helper 2 (Th2) lymphocyte responses. We investigated the role of host basophils
      in the induction of donor T cell responses and GVHD after allogeneic bone marrow
      transplantation. Elimination of host basophils did not alter the severity of GVHD
      induced mortality across multiple clinically relevant models of allogeneic bone
      marrow transplantation. Furthermore, induction of donor T cell proliferation and
      Th2 polarization was not altered significantly after depletion of host basophils.
      Our results demonstrate that, in contrast to their role in inducing Th2 responses
      in certain contexts, basophils are dispensable for the induction of donor Th2
      responses and for the severity of GVHD.

PMID- 21871864
TI  - Challenges and prospects for malaria elimination in the Southern Africa region.
AB  - The burden of malaria has decreased dramatically within the past several years in
      parts of sub-Saharan Africa, including regions of Southern Africa. Important to
      effective regional malaria control in Southern Africa is the appreciation that
      the reductions in malaria have not been achieved uniformly, with some countries
      experiencing resurgence. Understanding the reasons for sustained low-level
      malaria transmission in the face of control efforts, why malaria control efforts
      have not been successful in particular epidemiological settings and the
      epidemiological and transmission patterns following resurgence are critical to
      improving further malaria control and possible elimination. The overall goal of
      the International Center of Excellence for Malaria Research in Southern Africa is
      to contribute to regional malaria control efforts that can be sustained beyond
      the duration of the project. This goal will be achieved through a combination of:
      (1) state-of-the-art research on malaria epidemiology, vector biology and the
      genetics of the malaria parasite in three different epidemiological settings; (2)
      collaborations with national malaria control programs to develop locally adapted
      and sustainable control strategies; and (3) training, career development and
      capacity building at research institutions throughout the region.

PMID- 21871865
TI  - Optimal design for the dose-response screening of tight-binding enzyme
      inhibitors.
AB  - Optimal experimental designs for the dose-response screening of enzyme inhibitors
      were studied within the framework of the Box-Lucas theory. If the enzyme
      concentration E is considered as a fixed constant, an exact two-point D-optimal
      design consists of a pair of inhibitor concentrations equal to I(1)=0 and
      I(2)=E+K, where K is the apparent inhibition constant. If the enzyme
      concentration is treated as an adjustable parameter, an empirical three-point D
      optimal design consists of three inhibitor concentrations equal to I(1)=0,
      I(2)=E+3K, and I(3)=0.7E. These results were applied to design optimized,
      irregularly spaced concentration series for routine inhibitor screening. A
      heuristic Monte Carlo simulation study confirmed that the optimized dilution
      series is significantly more efficient than the classic series characterized by a
      constant dilution ratio. An online calculator to create optimized dilution series
      is freely available at http://www.biokin.com/design/.

PMID- 21871866
TI  - Lipophilic penetration enhancers and their impact to the bilayer structure of
      stratum corneum lipid model membranes: neutron diffraction studies based on the
      example oleic acid.
AB  - The present study analyzes the effect of the lipophilic penetration enhancer
      oleic acid on the bilayer structure of stratum corneum (SC) lipid model membranes
      based on Ceramide AP by using the neutron diffraction technique. Our results
      indicate the formation of a single lamellar phase in the presence of oleic acid
      under the chosen experimental conditions; a separated fluid-like oleic acid-rich
      phase was not detected in the present study. By comparing the internal membrane
      structure received from Fourier synthesis with the model system lacking oleic
      acid, considerable structural changes in terms of impairment of the lamellar
      order were found after incorporation of the penetration enhancer into the
      bilayers. In addition, by using specifically deuterated oleic acid we were able
      to prove the integration of the enhancer molecules into the model bilayers and
      moreover, to determine the exact position of oleic acid inside the SC lipid model
      membrane. From the present results we conclude a strong perturbation of lamellar
      SC lipid arrangement due to the intercalated penetration enhancer which can
      account for the promoting effects on drug penetration across the SC known for
      oleic acid.

PMID- 21871867
TI  - Electrophysiological properties of heteromeric TRPV4-C1 channels.
AB  - We previously reported that TRPV4 and TRPC1 can co-assemble to form heteromeric
      TRPV4-C1 channels [12]. In the present study, we characterized some basic
      electrophysiological properties of heteromeric TRPV4-C1 channels. 4alpha-Phorbol
      12,13-didecanoate (4alpha-PDD, a TRPV4 agonist) activated a single channel
      current in HEK293 cells co-expressing TRPV4 and TRPC1. The activity of the
      channels was abrogated by a TRPC1-targeting blocking antibody T1E3. Conductance
      of the channels was ~95pS for outward currents and ~83pS for inward currents. The
      channels with similar conductance were also recorded in cells expressing TRPV4-C1
      concatamers, in which assembled channels were expected to be mostly 2V4:2C1.
      Fluorescence Resonance Energy Transfer (FRET) experiments confirmed the formation
      of a protein complex with 2V4:2C1 stoichiometry while suggesting an unlikeliness
      of 3V4:1C1 or 1V4:3C1 stoichiometry. Monovalent cation permeability profiles were
      compared between heteromeric TRPV4-C1 and homomeric TRPV4 channels. For
      heteromeric TRPV4-C1 channels, their permeation profile was found to fit to
      Eisenman sequence VI, indicative of a strong field strength cation binding site,
      whereas for homomeric TRPV4 channels, their permeation profile corresponded to
      Eisenman sequence IV for a weak field strength binding site. Compared to
      homomeric TRPV4 channels, heteromeric TRPV4-C1 channels were slightly more
      permeable to Ca2+ and had a reduced sensitivity to extracellular Ca2+ inhibition.
      In summary, we found that, when TRPV4 and TRPC1 were co-expressed in HEK293
      cells, the predominate assembly type was 2V4:2C1. The heteromeric TRPV4-C1
      channels display distinct electrophysiological properties different from those of
      homomeric TRPV4 channels.

PMID- 21871868
TI  - Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely
      correlated with p16 expression.
AB  - Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young
      children. MRT is characterized by inactivation of integrase interactor 1 (INI1).
      Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for
      the proliferation of MRT cells. Here we investigated the effects of PD 0332991
      (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN,
      KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT
      YM, PD inhibited cell proliferation >50%, (IC(50) values 0.01 to 0.6 MUM) by WST
      8 assay, and induced G1-phase cell cycle arrest, as shown by flow cytometry and
      BrdU incorporation assay. The sensitivity of the MRT cell lines to PD was
      inversely correlated with p16 expression (r=0.951). KP-MRT-YM cells overexpress
      p16 and were resistant to the growth inhibitory effect of PD. Small interfering
      RNA against p16 significantly increased the sensitivity of KP-MRT-YM cells to PD
      (p<0.05). These results suggest that p16 expression in MRT could be used to
      predict its sensitivity to PD. PD may be an attractive agent for patients with
      MRT whose tumors express low levels of p16.

PMID- 21871869
TI  - Beneficial and harmful effects of alcohol exposure on Caenorhabditis elegans
      worms.
AB  - Alcoholic beverages are consumed widely throughout the world. While the harmful
      effects of alcoholism are well recognized, the beneficial effects of moderate
      alcohol consumption to human health remain debatable. In this study, we
      investigated the effects of long-term ethanol exposure on nematode Caenorhabditis
      elegans worms. At high concentrations (>= 4%), ethanol significantly impaired
      mobility, reduced fertility, and shortened lifespan. Interestingly, at low
      concentrations (1-2%), it extended lifespan, accompanied with a slower decline of
      mobility during aging, although it slightly impaired development, fertility, and
      chemotaxis. The lifespan-prolonging effects of ethanol at the low concentrations
      were seen in normal worms exposed to ethanol from egg, young larva, and young
      adult stages but were not observed in age-1 and sir-2.1 mutant worms. Our study
      demonstrated hormetic effects of ethanol and further established C. elegans as a
      suitable animal model to study ethanol related problems.

PMID- 21871870
TI  - A unique EF-hand motif in mnemiopsin photoprotein from Mnemiopsis leidyi:
      implication for its low calcium sensitivity.
AB  - Up to now, all reported Ca(2+)-regulated photoproteins, except for mnemiopsin,
      have been cloned and expressed in Escherichia coli. In this study, the cDNA for
      an isotype of mnemiopsin, from the ctenophore Mnemiopsis leidyi, has been cloned,
      sequenced, and functionally expressed. The full length cDNA encoding mnemiopsin
      of M. leidyi was 624 bp open reading frame encoding a protein of 207 amino acid
      residues with calculated molecular mass of ~24 kDa. The deduced amino acid
      sequence showed 90% and 84% identity to berovine (from ctenophore Beroe
      abyssicola) and bolinopsin 2 (from the ctenophore Bolinopsis infundibulum)
      respectively. In contrast to all known EF-hand in photoproteins, a unique EF-hand
      motif was found in mnemiopsin, in which a conserved glycine is substituted with
      glutamic acid. According to the results, the optimum pH was 9.0, time course of
      regeneration was 15 h and its Ca(2+) sensitivity was lower than aequorin. Results
      of pK(a) calculation for ionizable residues, motif scan and hydrophobic
      interactions of cavity aromatic residues of mnemiopsin in comparison with
      aequorin showed different patterns in these two photoproteins. In addition,
      experimental results are confirmed with the theoretical studies.

PMID- 21871871
TI  - Overexpression of PtADC confers enhanced dehydration and drought tolerance in
      transgenic tobacco and tomato: effect on ROS elimination.
AB  - Drought is a major environmental factor that limits plant growth and
      productivity. Polyamines have been shown to act as stress molecules that
      accumulate in plant adaptation to abiotic stresses. In this study, an arginine
      decarboxylase gene isolated from Poncirus trifoliata, PtADC, was introduced into
      tobacco and tomato to investigate its function in drought tolerance. We
      demonstrate that the transgenic plants showed an improvement in dehydration and
      drought tolerance. Under dehydration stress conditions, the accumulation of
      reactive oxygen species (ROS) was remarkably decreased in the transgenic lines as
      compared with the wild type. Moreover, the transcript levels of three stress
      responsive genes were increased in the transgenic tobacco lines. Taken together,
      our results suggest that PtADC plays a key role in drought tolerance, which is,
      at least partially, attributed to its role in ROS detoxification.

PMID- 21871872
TI  - Sterol regulatory element binding protein-1 (SREBP1) activation in motor neurons
      in excitotoxicity and amyotrophic lateral sclerosis (ALS): Indip, a potential
      therapeutic peptide.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor
      neurons in which glutamatergic excitotoxicity may participate. A recently
      characterized downstream effector of glutamatergic excitotoxicity is the
      activation of the lipid transcription factor sterol regulatory element binding
      protein-1 (SREBP1). Here we report that in spinal cord tissues of transgenic
      mouse model, G93A, as well as post-mortem spinal cord specimens of human familial
      and sporadic ALS, significant activation of SREBP1 following drastic degradation
      of ER membrane resident protein Insig-1. A TAT-fused short peptide (Indip) to
      prevent Insig-1 degradation and subsequent SREBP1 activation significantly
      protected cultured spinal cord neurons against glutamate-induced excitotoxicity.
      Indip or other SREBP1-pathway modulating compounds may prove beneficial in ALS.

PMID- 21871873
TI  - Bisphenol-A suppresses neurite extension due to inhibition of phosphorylation of
      mitogen-activated protein kinase in PC12 cells.
AB  - An endocrine disrupter, bisphenol-A is widely used in the production of plastics
      and coatings. Recently, it was reported that bisphenol-A affected
      neurotransmitters in the mammalian brain. On the basis of these reports, it was
      considered that bisphenol-A affected neuronal differentiation. In this study, the
      morphological changes in nerve growth factor (NFG)-induced differentiation caused
      by bisphenol-A were confirmed using a PC12 cell system. When a low concentration
      of bisphenol-A was added to medium containing NGF, it inhibited neurite
      extension. In addition, to clarify whether bisphenol-A affects the early and late
      stages of the NGF-signaling pathway in cell differentiation, changes of
      phosphorylation of MAP kinases and cAMP-response element binding protein (CREB)
      in PC12 cells treated with and without BPA in medium containing NGF were
      investigated using western blot analysis. As results, bisphenol-A significantly
      inhibited phosphorylation of CREB and ERK1/2 MAPK.

PMID- 21871874
TI  - The effect of lipids on the enzymatic activity of 6-phosphofructo-1-kinase from
      B. stearothermophilus.
AB  - 6-Phosphofructo-1-kinase (PFK-1), a major regulatory enzyme in the glycolysis
      pathway, is a cytoplasmic enzyme with complicated allosteric kinetics. Here we
      investigate the effects of lipids on the activity of PFK from Bacillus
      stearothermophilus (BsPFK), to determine whether BsPFK shares any of the membrane
      binding or lipid binding properties reported for some mammalian PFKs. Our results
      show that large unilamellar vesicles (LUVs) composed of either the phospholipid
      1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or of 1:1 (mole ratio) DOPC and
      the fatty acid, oleic acid (OA), cause a three-fold increase in V(max), depending
      on the lipid concentration and vesicle composition, but no change in K(m).
      Further studies show lipids do not reverse the allosteric inhibitory effects of
      phosphoenolpyruvate (PEP) on BsPFK. SDS/PAGE studies do not show significant
      binding of the BsPFK tetramer to the surface of the phospholipid vesicles,
      suggesting that modulation of catalytic activity is due to binding of lipid
      monomers. By simulating the kinetics of BsPFK interaction with vesicles and lipid
      monomers we conclude that the change in BsPFK catalytic activity with respect to
      lipid concentration is consistent with monomer abstraction from vesicles rather
      than direct uptake of lipid monomers from solution.

PMID- 21871875
TI  - Mid-regional pro atrial natriuretic peptide allows the accurate identification of
      patients with atrial fibrillation of short time of onset: a pilot study.
AB  - OBJECTIVES: Atrial fibrillation (AF) is a common arrhythmia; its most prevalent
      and devastating complication is stroke. A delay of AF onset >48 h is believed to
      be clinically significant. Mid-regional pro A-type natriuretic peptide (MR
      proANP) could be of interest in the identification of the time from onset of AF
      to presentation. DESIGN AND METHODS: We measured MR-proANP plasma concentration
      at presentation in consecutive patients in whom onset of AF was determined,
      without evidence of concomitant acute heart failure. RESULTS: Forty-seven
      patients were included. Patients with an AF onset <48 h (n=19) had decreased MR
      proANP concentrations versus patients with onset >48 h (144.0 [129.2-213.7]
      versus 321.7 [236.4-425.6] pmol/L, p<0.001); MR-proANP was the only independent
      variable associated with AF <48 h according to multivariate analysis. Area under
      the ROC curve for identify AF onset <48 h was 0.878 [95%CI 0.778-0.978].
      CONCLUSIONS: MR-proANP concentration may reliably identify the time from onset of
      AF to presentation.

PMID- 21871876
TI  - Effects of the Hb E, Hb H and Hb G-Taichung variants on HbA1c values by the Bio
      Rad variant II turbo analyzer.
AB  - OBJECTIVES: The influences of Hb variants on HbA(1c) values can cause
      mismanagement of diabetes; therefore, the effects of Hb E, H, and G-Taichung
      variants were evaluated. DESIGNS AND METHODS: HbA(1c) values of 2105 samples,
      including 37 samples with Hb E, H and G-Taichung variants identified by Hb
      electrophoresis and the PCR sequence, were evaluated by the ion-exchange (Bio-Rad
      Variant II Turbo analyzer) and boronate affinity (Primus CLC 385 analyzer) high
      performance liquid chromatography (HPLC) methods. RESULTS: In the patients with
      the Hb E and H variants, their HbA(1c) values determined by ion-exchange HPLC
      were significantly higher than those by boronate affinity HPLC. However, there
      were no significant differences of the HbA(1c) values in the patients with the Hb
      G-Taichung variant. CONCLUSIONS: The HbA1c levels might be interfered by the Hb E
      and H variants, but not the Hb G-Taichung variant, measured by the Bio-Rad
      Variant II Turbo analyzer.

PMID- 21871878
TI  - A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via
      inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells.
AB  - Multidrug resistance (MDR) is a major impediment to the effective chemotherapy of
      many human malignancies, and novel MDR reversal agents are desirable for
      combination therapy to reduce MDR, enhance anti-tumor activity and reduce side
      effects. Overexpression of P-glycoprotein (P-gp) is the most prevalent cause of
      MDR in cancer tissues, and resistance to apoptosis is a common characteristic for
      the multidrug resistant cancer cells. Our group has synthesized a novel potent
      anti-tumor indirubin derivative, PHII-7. In this study, MCF-7/ADR cells, an
      adriamycin (ADR)-selected human breast tumor cell line with the MDR phenotype,
      were used to investigate the anticancer properties of this novel indirubin
      derivative. Cytotoxicity and apoptosis assays showed that PHII-7 significantly
      inhibited cell growth, induced apoptosis, potentiated ADR cytotoxicity and
      restored chemotherapy sensitivity in the MDR cancer cells. Further studies
      indicated that by down-regulation of P-gp expression, PHII-7 partially inhibited
      P-gp efflux pump function and increased intracellular accumulation of Rhodamine
      123, a P-gp substrate. These results provide a biochemical basis for possible
      clinical application of PHII-7 alone or in combination with conventional
      antineoplastic agents in the treatment MDR tumors.

PMID- 21871877
TI  - The cytoplasmic domain of TGFbetaR3 through its interaction with the scaffolding
      protein, GIPC, directs epicardial cell behavior.
AB  - The epicardium is a major contributor of the cells that are required for the
      formation of coronary vessels. Mice lacking both copies of the gene encoding the
      Type III Transforming Growth Factor beta Receptor (TGFbetaR3) fail to form the
      coronary vasculature, but the molecular mechanism by which TGFbetaR3 signals
      coronary vessel formation is unknown. We used intact embryos and epicardial cells
      from E11.5 mouse embryos to reveal the mechanisms by which TGFbetaR3 signals and
      regulates epicardial cell behavior. Analysis of E13.5 embryos reveals a lower
      rate of epicardial cell proliferation and decreased epicardially derived cell
      invasion in Tgfbr3(-/-) hearts. Tgfbr3(-/-) epicardial cells in vitro show
      decreased proliferation and decreased invasion in response to TGFbeta1 and
      TGFbeta2. Unexpectedly, loss of TGFbetaR3 also decreases responsiveness to two
      other important regulators of epicardial cell behavior, FGF2 and HMW-HA.
      Restoring full length TGFbetaR3 in Tgfbr3(-/-) cells rescued deficits in invasion
      in vitro in response TGFbeta1 and TGFbeta2 as well as FGF2 and HMW-HA. Expression
      of TGFbetaR3 missing the 3 C-terminal amino acids that are required to interact
      with the scaffolding protein GIPC1 did not rescue any of the deficits.
      Overexpression of GIPC1 alone in Tgfbr3(-/-) cells did not rescue invasion
      whereas knockdown of GIPC1 in Tgfbr3(+/+) cells decreased invasion in response to
      TGFbeta2, FGF2, and HMW-HA. We conclude that TGFbetaR3 interaction with GIPC1 is
      critical for regulating invasion and growth factor responsiveness in epicardial
      cells and that dysregulation of epicardial cell proliferation and invasion
      contributes to failed coronary vessel development in Tgfbr3(-/-) mice.

PMID- 21871879
TI  - Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on
      nicotine self-administration.
AB  - 18-Methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown
      to decrease the self-administration of several drugs of abuse in rats. 18-MC is a
      potent antagonist at alpha3beta4 nicotinic receptors. Consistent with high
      densities of alpha3beta4 nicotinic receptors being located in the medial habenula
      and the interpeduncular nucleus, 18-MC has been shown to act in these regions to
      decrease both morphine and methamphetamine self-administration. The present study
      was conducted to determine if 18-MC's effect on nicotine self-administration is
      mediated by acting in these same brain regions. Because moderate densities of
      alpha3beta4 receptors occur in the dorsolateral tegmentum, ventral tegmental
      area, and basolateral amygdala, these brain areas were also examined as potential
      sites of action of 18-MC. Local administration of 18-MC into either the medial
      habenula, the basolateral amygdala or the dorsolateral tegmentum decreased
      nicotine self-administration. Surprisingly, local administration of 18-MC into
      the interpeduncular nucleus increased nicotine self-administration while local
      administration of 18-MC into the ventral tegmental area had no effect on nicotine
      self-administration. Similar effects were produced by local administration of
      either mecamylamine or conotoxin AuIB. These data are consistent with the
      hypothesis that 18-MC decreases nicotine self-administration by indirectly
      modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4
      nicotinic receptors in the medial habenula, basolateral amygdala, and
      dorsolateral tegmentum. The data also suggest that an action of 18-MC in the
      interpeduncular nucleus may attenuate aversive and/or depressive effects of
      nicotine.

PMID- 21871880
TI  - Construction and characterization of hepatocyte nuclear factor HNF4alpha1 over
      expressing cell line derived from human hepatoma HepG2 cells.
AB  - Cancer cell lines derived from hepatocytes have an altered phenotype and they
      lack hepatocyte-specific functions. It is at least partly due to the under
      expression of transcription factors such as hepatocyte nuclear factor 4alpha
      (HNF4alpha), steroid receptor co-activator 1 (SRC1) etc. Recently, a strategy of
      transient transfection of human hepatic cells with HNF4alpha revealed improved
      hepatospecific functions, including the expression of drug-metabolizing enzymes.
      In the current study we established a human cell line derived from HepG2 cells
      stably transfected with human HNF4alpha, and we examined this line for
      hepatospecific markers. Of the 9 clones analyzed, we found an increased secretion
      of fibrinogen (9 clones), albumin (5 clones) and plasminogen (3 clones), while
      secretion of alpha1-antitrypsin was not changed. The expression of pregnane X
      receptor (PXR) and aryl hydrocarbon receptor (AhR) proteins but not mRNAs was
      slightly increased. TCDD-dependent induction of CYP1A1 mRNA and protein was
      augmented in 50% of clones, but there was no correlation between the CYP1A1
      inducibility and expression levels of AhR and HNF4alpha. Induction of CYP3A4 mRNA
      by rifampicin was about 1.5-2.5 fold (clones 2, 4, 6, 7) and it was not
      significantly different from CYP3A4 mRNA induction in parent HepG2. The basal
      expression of CYP3A4 protein was increased in all clones, but rifampicin-induced
      expression of CYP3A4 protein was in all clones lower than in parent HepG2.
      Overall, the stable over-expression of HNF4alpha in HepG2 cells restores some of
      the hepatospecific functions, but it has a minor effect on the expression of
      xenobiotic-metabolizing enzymes and their regulators.

PMID- 21871882
TI  - Cloning and pharmacological characterization of the dog cannabinoid CB2receptor.
AB  - Comparison of human, rat and mouse cannabinoid CB(2) receptor primary sequences
      has shown significant divergence at the mRNA and protein sequence level, raising
      the possibility of species specific pharmacological properties. Additionally,
      given the importance of the dog as a non-rodent species for predicting human
      safety during the drug development process, we cloned the dog CB(2) receptor gene
      and characterized its in-vitro pharmacological properties in a recombinant
      expression system. A 1.1 kb dog peripheral cannabinoid receptor (dCB(2)) fragment
      encoding a 360 amino acid protein was cloned from dog spleen cDNA. Analysis of
      the cloned dCB(2) polypeptide sequence revealed that it shares between 76 and 82%
      homology with rat, mouse, human and predicted chimpanzee cannabinoid CB(2)
      receptors. The dog CB(2) receptor expressed in CHO cells displayed similar
      binding affinities for various synthetic and endogenous cannabinoids as compared
      to those measured for the human and rat cannabinoid CB(2) receptors. However,
      these ligands exhibited altered functional potencies and efficacies for the dog
      cannabinoid CB(2) receptor, which was also found to be negatively coupled to
      adenylate cyclase activity. These complex pharmacological differences observed
      across species for the cannabinoid CB(2) receptor suggest that caution should be
      exerted when analyzing the outcome of animal efficacy and safety studies, notably
      those involving cannabinoid CB(2) receptor targeting molecules tested in the dog.

PMID- 21871883
TI  - Inhibiting effects of Leflunomide metabolite on overexpression of CD147, MMP-2
      and MMP-9 in PMA differentiated THP-1 cells.
AB  - Recent studies have reported elevated expression of cluster of differentiation
      (CD) 147 on CD14(+) monocytes of the peripheral blood of patients with active
      rheumatoid arthritis and a correlation of CD147 expression with Disease Activity
      Score. Thus, CD147 may be a new target for treatment of rheumatoid arthritis.
      Leflunomide is a disease-modifying antirheumatic drug that is commonly used to
      treat rheumatoid arthritis. The effect of leflunomide in blocking the up
      regulation of CD147 and in blocking the down-regulation of metalloproteinases
      (MMP)-2 and MMP-9 in active macrophages has not yet been established. In this
      study we investigated the effect of A771726, the active metabolite of
      leflunomide, on expression of CD147 and on the gelatinolytic activity of MMP-2
      and MMP-9 in phorbol myristate acetate (PMA) differentiated THP-1 cells. The
      expression of CD147, MMP-2, and MMP-9 mRNAs were determined by real-time
      quantitative reverse transcription PCR, the levels of cellular surface expression
      of CD147 were determined by flow cytometry, and the gelatinolytic activity of MMP
      2 and MMP-9 were determined by zymography. Our results showed that A771726
      significantly inhibited the expression of CD147 on the cell surface of activated
      THP-1 cells in a dose-dependent manner (P<0.01), inhibited the expression of MMP
      2 and MMP-9 mRNAs in a dose-dependent manner (P<0.01), and inhibited the
      gelatinolytic activity of MMP-2 and MMP-9 at concentration of 15 MUg/ml and 45
      MUg/ml (P<0.01). Our results indicate that A771726, the active metabolite of
      leflunomide, inhibited CD147 expression at the protein level and inhibited
      gelatinolytic activity of MMP-2 and MMP-9 in PMA-differentiated THP-1 cells.

PMID- 21871881
TI  - Eicosapentaenoic acid regulates IkappaBalpha and prevents tubulointerstitial
      injury in kidney.
AB  - Fish oil containing n-3 polyunsaturated fatty acids such as eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) is well known to prevent the progression of
      IgA nephropathy. However, the mechanism through which fish oil prevents the
      progression of renal injury remains uncertain. We tried to clarify the effects of
      EPA on tubulointerstitial injury in the kidney both in vivo and in vitro. We
      examined the effects of EPA, especially to focus on nuclear factor kappa B (NF
      kappaB), using Thy-1 nephritis models. Also the mechanism of EPA was investigated
      using small-interfering RNA (siRNA) in lipopolysaccharide (LPS)-stimulated
      proximal tubular epithelial cells (PTECs). In Thy-1 nephritis models, EPA
      significantly inhibited tubulointerstitial injury and the infiltration of
      macrophages into tubulointerstitial lesions except severe glomerular injury at
      early stage. Compared with control animals, NF-kappaB activation was
      significantly augmented in the Thy-1 nephritic kidney. However, treatment with
      EPA significantly reduced NF-kappaB activation, down-regulated the expressions of
      NF-kappaB-dependent molecules. Also in LPS-stimulated PTECs, LPS augmented NF
      kappaB activation and the expression of NF-kappaB-dependent molecules. As in the
      case with the Thy-1 nephritis models, treatment with EPA inhibited them,
      prevented the degradation of IkappaBalpha in LPS-stimulated PTECs. Pre-treatment
      with siRNA for IkappaBalpha abolished the inhibitory effect of EPA on LPS-induced
      NF-kappaB activation, suggesting that EPA inhibited NF-kappaB activation by
      regulating IkappaBalpha. Our results indicate that EPA prevents the early
      progression of tubulointerstitial injury in Thy-1 nephritis models, and the
      inhibitory effect of EPA on the expression of inflammatory molecules via the
      regulation of IkappaBalpha in cultured cells may explain this mechanism.

PMID- 21871884
TI  - Interaction between ciprofloxacin and melanin: the effect on proliferation and
      melanization in melanocytes.
AB  - There have been described serious adverse events caused by ciprofloxacin in
      pigmented tissues. It is known that some fluoroquinolones bind well to melanin
      rich tissues, but the relation between their affinity to melanin and the skin or
      eye toxicity is not well documented. The aim of this study was to examine whether
      ciprofloxacin binds to melanin, and how this interaction affects the
      proliferation and melanization in melanocytes. We have demonstrated that
      complexes which ciprofloxacin forms with melanin possess at least two classes of
      independent binding sites. Their association constants are K(1)~10(5) M(-1) and
      K(2)~10(2) M(-1), respectively. Ciprofloxacin has induced evident concentration
      dependent loss in melanocytes viability. The value of ED(50) was found to be ~0.5
      mM. It has also been shown that ciprofloxacin reduces melanin content, and
      decreases tyrosinase activity in human skin melanocytes. The ability of
      ciprofloxacin to interact with melanin and its inhibitory effect on melanization
      in melanocytes in vitro may explain a potential role of melanin in the mechanisms
      of ciprofloxacin toxic effects in vivo.

PMID- 21871885
TI  - Vasodilation of retinal arterioles induced by activation of BKCa channels is
      attenuated in diabetic rats.
AB  - The large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels modulate the
      retinal vascular tone, but question of whether the impairment of the channel
      function contributes to abnormalities of retinal circulation has not yet been
      completely elucidated. The purpose of this study was to examine effects of
      diabetes on the vasodilation induced by activation of BK(Ca) channels. Male
      Wistar rats were treated with streptozotocin and experiments were performed 2
      weeks later. The streptozotocin-treated animals were given drinking water
      containing 5% d-glucose to shorten the term in the development of retinal
      vascular dysfunction. The retinal vascular responses were assessed by measuring
      diameter of retinal arterioles in the fundus images that were captured with an
      original fundus camera system. In non-diabetic rats, vasodilator effects of
      acetylcholine on retinal arterioles were significantly reduced by iberiotoxin, an
      inhibitor of BK(Ca) channels. However, the inhibitory effect of iberiotoxin was
      not observed in diabetic rats, and the responses to the BK(Ca) channel opener BMS
      191011 were almost completely abolished. The retinal vasodilator response to
      acetylcholine, possibly an endothelium-derived hyperpolarizing factor-mediated
      response, observed after treatment with N(G)-nitro-l-arginine methyl ester and
      indomethacin was markedly reduced in diabetic rats. The responses to pinacidil,
      an opener of ATP-sensitive K(+) channels, were unchanged. These results suggest
      that the retinal vasodilator response mediated through mechanisms involving
      activation of BK(Ca) channels is diminished at the early stage of diabetes in
      rats. The impairment of BK(Ca) channel function may contribute to abnormal
      retinal hemodynamics in diabetes and consequently play an important role in the
      pathogenesis of diabetic retinopathy.

PMID- 21871887
TI  - Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain
      plasticity.
AB  - Chondroitin sulphate proteoglycans (CSPGs) are a family of inhibitory
      extracellular matrix molecules that are highly expressed during development,
      where they are involved in processes of pathfinding and guidance. CSPGs are
      present at lower levels in the mature CNS, but are highly concentrated in
      perineuronal nets where they play an important role in maintaining stability and
      restricting plasticity. Whilst important for maintaining stable connections, this
      can have an adverse effect following insult to the CNS, restricting the capacity
      for repair, where enhanced synapse formation leading to new connections could be
      functionally beneficial. CSPGs are also highly expressed at CNS injury sites,
      where they can restrict anatomical plasticity by inhibiting sprouting and
      reorganisation, curbing the extent to which spared systems may compensate for the
      loss function of injured pathways. Modification of CSPGs, usually involving
      enzymatic degradation of glycosaminoglycan chains from the CSPG molecule, has
      received much attention as a potential strategy for promoting repair following
      spinal cord and brain injury. Pre-clinical studies in animal models have
      demonstrated a number of reparative effects of CSPG modification, which are often
      associated with functional recovery. Here we discuss the potential of CSPG
      modification to stimulate restorative plasticity after injury, reviewing evidence
      from studies in the brain, the spinal cord and the periphery.

PMID- 21871888
TI  - Transcriptional repression of the tumor suppressor DRO1 by AIB1.
AB  - Using transcriptomic gene expression profiling we found tumor suppressor DRO1
      being repressed in AIB1 transgenic mice. In agreement, AIB1 represses DRO1
      promoter and its expression levels inversely correlate with DRO1 in several
      cancer cell lines and in ectopic and silencing assays. Estrogen modulators
      treatment showed a regulation in an estrogen receptor-dependent fashion.
      Importantly, DRO1 overexpression resulted in BCLAF1 upregulation, a compelling
      concept given that BCLAF1 is a death-promoting transcriptional repressor.
      Additionally, DRO1 shuttles from Golgi to the endoplasmic reticulum upon
      apoptotic stimuli, where it is predicted to facilitate the apoptosis cascade.
      Finally, DRO1 repression is an important factor for AIB1-mediated inhibition of
      apoptosis. Collectively, our results reveal DRO1 as an AIB1-targeted tumor
      suppressor, providing a novel mechanism for AIB1-dependent inhibition of
      apoptosis.

PMID- 21871886
TI  - The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth
      inhibitory and differentiation signaling via androgen receptor downregulation in
      prostate cancer cells.
AB  - Upregulated ERK1/2 activity is correlated with androgen receptor (AR)
      downregulation in certain prostate cancer (PCa) that exhibits androgen
      deprivation-induced neuroendocrine differentiation, but its functional relevance
      requires elucidation. We found that sustained ERK1/2 activation using active Raf
      or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein
      levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by
      proteasome inhibitors, MG132 and bortezomib, indicating that the pathway
      regulation is mediated at multiple points. Ectopic expression of a constitutively
      active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation
      markers, neuron-specific enolase and neutral endopeptidase, and the cyclin
      dependent kinase inhibitors, p16(INK4A) and p21(CIP1), but not Rb phosphorylation
      and E2F1 expression, indicating that AR has a specific role in the pathway
      mediated differentiation and growth inhibitory signaling. However, despite the
      sufficient role of Raf/MEK/ERK, its inhibition using U0126 or ERK1/2 knockdown
      could not block androgen deprivation-induced AR downregulation in an LNCaP
      neuroendocrine differentiation model, suggesting that additional signaling
      pathways are involved in the regulation. We additionally report that sustained
      Raf/MEK/ERK activity can downregulate full length as well as hormone binding
      domain-deficient AR isoforms in androgen-refractory C4-2 and CWR22Rv1, but not in
      LAPC4 and MDA-PCa-2b. Our study demonstrates a novel role of the Raf/MEK/ERK
      pathway in regulating AR expression in certain PCa types and provides an insight
      into PCa responses to its aberrant activation.

PMID- 21871889
TI  - Structural basis of coagulation factor V recognition for cleavage by RVV-V.
AB  - Russell's viper venom factor V (FV) activator (RVV-V) is a thrombin-like
      proteinase that specifically cleaves the Arg1545-Ser1546 bond of FV. Here we
      present the crystal structure of RVV-V in complex with the FV14 peptide (residues
      1533-1546 of human FV) determined at 1.8A resolution. The structure reveals
      multiple interactions between RVV-V and the seven residues, Ile1539 (P(7))
      Arg1545 (P(1)), of the cleaved substrate. Comparison with substrate-free
      structures reveals conformational changes of the RVV-V loops upon substrate
      binding, suggesting that the multiple interactions are mediated by an induced-fit
      mechanism. The results provide an explanation for the narrow specificity of RVV
      V.

PMID- 21871890
TI  - Tetrahydrobiopterin is functionally distinguishable from tetrahydrodictyopterin
      in Dictyostelium discoideum Ax2.
AB  - Dictyostelium discoideum Ax2 produces both L-erythro-tetrahydrobiopterin (BH4)
      and its stereoisomer D-threo-BH4 (DH4). The putative cofactor function of them
      for phenylalanine hydroxylase (PAH) was investigated through genetic manipulation
      and quantitative determination of pteridines. In addition to establishing that
      dihydropteridine reductase (DHPR) and dihydrofolate reductase (DHFR) constitute
      the regeneration pathway of both BH4 and DH4, the results suggested that BH4 is a
      preferential cofactor for PAH in vivo, not a secondary product of DH4, which
      functions mainly as an antioxidant. Our result also demonstrated that PAH may be
      essential for Dictyostelium growth in nature, and thus it appears that the
      organism has evolved a strategy to maintain BH4 level via regeneration pathway at
      the expense of DH4 under oxidative stress conditions.

PMID- 21871891
TI  - Novel effects of CCN3 that may direct the differentiation of chondrocytes.
AB  - Identification and characterization of local molecules directing the
      differentiation of chondrocytes to either transient or permanent cartilage are
      major issues in cartilage biology. Here, we found CCN family protein 3 (CCN3) was
      abundantly produced in rat developing epiphyseal cartilage. Evaluations in vitro
      showed that CCN3 repressed epiphyseal chondrocyte proliferation, while promoting
      matrix production in multiple assays performed. Furthermore, CCN3 enhanced the
      articular chondrocytic phenotype; whereas it repressed the one representing
      endochondral ossification. Additionally, the phenotype of growth plate
      chondrocytes and chondrogenic progenitors also appeared to be affected by CCN3 in
      a similar manner. These findings suggest a significant role of CCN3 in inducing
      chondrocytes to articular ones during joint formation.

PMID- 21871892
TI  - Yos9, a control protein for misfolded glycosylated and non-glycosylated proteins
      in ERAD.
AB  - The endoplasmic reticulum (ER) is responsible for folding and delivery of
      secretory proteins to their site of action. One major modification proteins
      undergo in this organelle is N-glycosylation. Proteins that cannot fold properly
      will be directed to a process known as endoplasmic reticulum associated
      degradation (ERAD). Processing of N-glycans generates a signal for ERAD. The
      lectin Yos9 recognizes the N-glycan signal of misfolded proteins and acts as a
      gatekeeper for the delivery of these substrates to the cytoplasm for degradation.
      Presence of Yos9 accelerates degradation of the glycosylated model ERAD substrate
      CPY*. Here we show that Yos9 has also a control function in degradation of the
      unglycosylated ERAD substrate CPY*0000. It decelerates its degradation rate.

PMID- 21871893
TI  - How does diet affect fecal steroid hormone metabolite concentrations? An
      experimental examination in red squirrels.
AB  - A growing number of longitudinal studies in free-ranging animals are measuring
      fecal steroid hormone metabolite concentrations (FHM). Free-ranging animals can
      exhibit major seasonal changes in their diet, yet we know relatively little about
      how diet affects FHM. We experimentally manipulated the diets of female and male
      North American red squirrels (Tamiasciurus hudsonicus) to determine how diet
      affected fecal cortisol (FCM) and androgen (FAM) metabolite concentrations. We
      measured FCM using an enzyme immunoassay (EIA) that we have previously validated
      and measured FAM using an assay we have previously validated for use in females
      and validate for males herein. We validated our EIA to measure FAM in males by
      identifying that 44.5+/-0.05% of recovered radiolabeled testosterone was excreted
      in the feces, our EIA antibody detected the fecal testosterone metabolites, and
      males with scrotal testes had significantly higher FAM (3.02+/-0.06 lnng/g dry
      feces) than those with abdominal testes (2.73+/-0.06). We initially fed all
      squirrels the same diet, but then switched one group of squirrels to a diet
      consisting of conifer seed (n=4 squirrels) whereas the other group was switched
      to peanut butter (n=7). FCM and FAM in squirrels fed conifer seed significantly
      increased from 0 to 94 h after their diets were changed. FCM in squirrels fed
      peanut butter significantly declined, whereas FAM declined but not significantly.
      This demonstrates that change in dietary fiber consumption (peanut butter versus
      conifer seed) or even slight differences in diet (conifer versus sunflower seeds)
      can strongly influence FHM.

PMID- 21871894
TI  - Influence of temperature regime on endocrine parameters and vitellogenesis during
      experimental maturation of European eel (Anguilla anguilla) females.
AB  - We examined the effect of temperature in European silver eels during their
      maturation induced by injections of carp pituitary extract on endocrine
      parameters: pituitary fshbeta and lhbeta expression, plasma 17beta-estradiol (E2)
      and vitellogenin, estrogen receptor 1 (esr1), and vitellogenin 2 (vtg2)
      expression in liver. A variable thermal regime (T10) that increased from 10
      degrees  to 14 degrees  and 17 degrees C was compared with a constant 20 degrees
      C regime (T20) during 12 weeks. T10 caused a faster development until week 8,
      higher fshbeta, lhbeta, esr1 expression, and higher E2 levels. The results
      strongly suggest that T10 is inducing a higher endogenous FSH level which
      increases the E2 circulating level during vitellogenesis. A variable thermal
      regime induced an fshbeta expression and E2 profile in vitellogenic hormonally
      matured eel females that were more similar to the profile observed in other
      naturally maturing fish.

PMID- 21871895
TI  - Cloning and expression pattern of the ecdysone receptor and retinoid X receptor
      from the centipede Lithobius peregrinus (Chilopoda, Lithobiomorpha).
AB  - In arthropods, molting events are mediated by the binding of the ecdysone hormone
      to a heterodimer of two nuclear receptors: the ecdysone receptor (EcR) and the
      retinoid X receptor (RXR), a homolog of ultraspiracle (USP). We have cloned
      partial sequences of several isoforms for EcR and RXR genes from the centipede
      Lithobius peregrinus, and studied their expression profile during the second post
      embryonic stage. LpEcR and LpRXR inferred amino acid sequences are very similar
      to other arthropod orthologs, especially to those of chelicerates and
      hemimetabolous insects, and their expression levels are significantly higher
      during the 48 h that precede the molt. Results obtained in this study represent
      the first data on the genetic basis of the ecdysone signal pathway for a
      myriapod, and in particular for an animal that, through a stereotyped
      developmental schedule paced by the molt cycle, completes trunk segmentation
      during post-embryonic life.

PMID- 21871896
TI  - MAp19, the alternative splice product of the MASP2 gene.
AB  - The lectin pathway of complement is a central part of innate immunity, but as a
      powerful inducer of inflammation it needs to be tightly controlled. The MASP2
      gene encodes two proteins, MASP-2 and MAp19. MASP-2 is the serine protease
      responsible for lectin pathway activation. The smaller alternative splice
      product, MAp19, lacks a catalytic domain but retains two of three domains
      involved in association with the pattern-recognition molecules (PRMs): mannan
      binding lectin (MBL), H-ficolin, L-ficolin and M-ficolin. MAp19 reportedly acts
      as a competitive inhibitor of MASP-2-mediated complement activation. In light of
      a ten times lower affinity of MAp19, versus MASP-2, for association with the
      PRMs, much higher serum concentrations of MAp19 than MASP-2 would be required for
      MAp19 to exert such an inhibitory activity. Just four amino acid residues
      distinguish MAp19 from MASP-2, and these are conserved between man, mouse and
      rat. Nonetheless we generated monoclonal rat anti-MAp19 antibodies and
      established a quantitative assay. We found the concentration of MAp19 in serum to
      be 217 ng/ml, i.e., 11nM, comparable to the 7 nM of MASP-2. In serum all MASP-2,
      but only a minor fraction of MAp19, was associated with PRMs. In contrast to
      previous reports we found that MAp19 could not compete with MASP-2 for binding to
      MBL, nor could it inhibit MASP-2-mediated complement activation.
      Immunohistochemical analyses combined with qRT-PCR revealed that both MAp19 and
      MASP-2 were mainly expressed in hepatocytes. High levels of MAp19 were found in
      urine, where MASP-2 was absent.

PMID- 21871897
TI  - Sarcoplasmic reticulum Ca2+ release in neonatal rat cardiac myocytes.
AB  - In the neonatal mammalian heart, the role of ryanodine receptor (=Ca(2+) release
      channel)-mediated sarcoplasmic reticulum (SR) Ca(2+) release for excitation
      contraction coupling is still a matter of debate. Using an adenoviral system, we
      overexpressed separately the junctional SR proteins triadin, junctin, and
      calsequestrin, which are probably involved in regulation of ryanodine receptor
      function. Infection of neonatal rat cardiac myocytes with triadin, junctin, or
      calsequestrin viruses, controlled by green fluorescent protein expression,
      resulted in an increased protein level of the corresponding transgenes.
      Measurement of Ca(2+) transients of infected cardiac myocytes revealed unchanged
      peak amplitudes under basal conditions but with overexpression of calsequestrin
      and triadin caffeine-releasable SR Ca(2+) content was increased. Our results
      demonstrate that an increased expression of triadin or calsequestrin is
      associated with an increased SR Ca(2+) storage but unchanged Ca(2+) signaling in
      neonatal rat cardiac myocytes. This is consistent with an ancillary role of the
      sarcoplasmic reticulum in excitation-contraction coupling in the developing
      mammalian heart.

PMID- 21871898
TI  - A mathematical framework for functional mapping of complex phenotypes using delay
      differential equations.
AB  - All biological phenomena occurring at different levels of organization from cells
      to organisms can be modeled as a dynamic system, in which the underlying
      components interact dynamically to comprehend its biological function. Such a
      systems modeling approach facilitates the use of biochemically and biophysically
      detailed mathematical models to describe and quantify "living cells," leading to
      an in-depth and precise understanding of the behavior, development and function
      of a biological system. Here, we illustrate how this approach can be used to map
      genes or quantitative trait loci (QTLs) that control a complex trait using the
      example of the circadian rhythm system which has been at the forefront of
      analytical mathematical modeling for many years. We integrate a system of
      biologically meaningful delay differential equations (DDEs) into functional
      mapping, a statistical model designed to map dynamic QTLs involved in biological
      processes. The DDEs model the ability of circadian rhythm to generate
      autonomously sustained oscillations with a period close to 24h, in terms of time
      varying mRNA and protein abundances. By incorporating the Runge-Kutta fourth
      order algorithm within the likelihood-based context of functional mapping, we
      estimated the genetic parameters that define the periodic pattern of QTL effects
      on time-varying mRNA and protein abundances and their dynamic association as well
      as the linkage disequilibrium of the QTL and a marker. We prove theorems about
      how to choose appropriate parameters to guarantee periodic oscillations. We
      further used simulation studies to investigate how a QTL influences the period
      and the amplitude of circadian oscillations through changing model parameters.
      The model provides a quantitative framework for assessing the interplay between
      genetic effects of QTLs and rhythmic responses.

PMID- 21871899
TI  - A mathematical model of cartilage regeneration after cell therapy.
AB  - Autologous Chondrocyte Implantation (ACI) is a cell-based therapy used mainly for
      the treatment of chondral defects in the knee. It involves surgically inserting
      isolated chondrocytes or mesenchymal stem cells (MSCs), previously expanded in
      culture, into the defect region. These chondrocytes then proliferate and migrate
      in the process forming extracellular matrix (ECM) and new cartilage. In the case
      of MSCs, the process of forming new cartilage is initiated only after
      differentiation of the stem cells into chondrocytes. Many details of the repair
      process following insertion in humans are unknown. To enable better understanding
      of the repair process, we present a mathematical model of cartilage regeneration
      after cell therapy. The key mechanisms involved in the regeneration process are
      simulated by modelling cell migration, proliferation and differentiation,
      nutrient diffusion and depletion, and ECM synthesis and degradation at the defect
      site, both spatially and temporally. The model successfully simulates the
      progression of cartilage regeneration. The model predicts a time frame of about
      18months for the defect to reach full maturation which corresponds with results
      from clinical studies and demonstrates that cartilage regeneration is a slow
      process. Moreover, the model also suggests that regeneration using stem cells
      alone is no better than that using chondrocytes. The stem cells need to first
      differentiate into chondrocytes before forming ECM and new cartilage, a process
      that is initiated only after the stem cell density exceeds a threshold value.
      Furthermore, with chondrocytes alone, the matrix seems to develop from the
      subchondral bone interface as compared to the normal cartilage interface, in the
      case of stem cells alone. The influence of initial conditions and parameters,
      such as the initial cell seeding densities and cell proliferation rates, is shown
      to not significantly influence the general evolution characteristics other than
      accelerating the initial growth process. The model presented here is a first
      approach towards better understanding of cartilage regeneration after cell
      therapy techniques.

PMID- 21871900
TI  - Bistability in a differential equation model of oyster reef height and sediment
      accumulation.
AB  - Native oyster populations in Chesapeake Bay have been the focus of three decades
      of restoration attempts, which have generally failed to rebuild the populations
      and oyster reef structure. Recent restoration successes and field experiments
      indicate that high-relief reefs persist, likely due to elevated reef height which
      offsets heavy sedimentation and promotes oyster survival, disease resistance and
      growth, in contrast to low-relief reefs which degrade in just a few years. These
      findings suggest the existence of alternative stable states in oyster reef
      populations. We developed a mathematical model consisting of three differential
      equations that represent volumes of live oysters, dead oyster shells (=accreting
      reef), and sediment. Bifurcation analysis and numerical simulations demonstrated
      that multiple nonnegative equilibria can exist for live oyster, accreting reef
      and sediment volume at an ecologically reasonable range of parameter values; the
      initial height of oyster reefs determined which equilibrium was reached. This
      investigation thus provides a conceptual framework for alternative stable states
      in native oyster populations, and can be used as a tool to improve the likelihood
      of success in restoration efforts.

PMID- 21871902
TI  - L-Dihydroxyphenylalanine modulates the steady-state expression of mouse striatal
      tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine and its
      metabolites in an MPTP mouse model of Parkinson's disease.
AB  - AIMS: l-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective symptomatic
      treatment for Parkinson's disease (PD), but PD patients usually experience a
      successful response to L-DOPA therapy followed by a progressive loss of response.
      L-DOPA efficacy relies on its decarboxylation by aromatic l-amino acid
      decarboxylase (AAAD) to form dopamine (DA). So exogenous L-DOPA drives the
      reaction and AAAD becomes the rate limiting enzyme in the supply of DA. In turn,
      exogenous L-DOPA regulates the expression and activity of AAAD as well as the
      synthesis of DA and its metabolites, changes that may be linked to the efficacy
      and side-effects of L-DOPA. MAIN METHODS: One-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse PD model was utilized to study the effects of L
      DOPA on the steady-state level and activity of AAAD, tyrosine hydroxylase (TH),
      DA and the metabolites of DA. The MPTP and control mice were treated twice daily
      with PBS or with 100mg/kg of L-DOPA for 14days and the expression and activity of
      AAAD, the expression of TH and the levels of DA and its metabolites were
      determined 24h after L-DOPA or PBS treatment, when exogenous L-DOPA is
      eliminated. KEY FINDINGS: In the MPTP model, L-DOPA reduced the steady-state
      expression and the activity of striatal AAAD by 52% and 50%, respectively, DA and
      metabolites were also significantly decreased. SIGNIFICANCE: The outcome shows
      that while L-DOPA replenishes striatal DA it also down-regulates AAAD and the
      steady-state synthesis and metabolic capability of the dopaminergic system. These
      findings are important in the precipitation of L-DOPA induced side effects and
      the management of L-DOPA therapy.

PMID- 21871901
TI  - Host immune responses that promote initial HIV spread.
AB  - The host inflammatory response to HIV invasion is a necessary component of the
      innate antiviral activity that vaccines and early interventions seek to
      exploit/enhance. However, the response is dependent on CD4+ T-helper cell 1 (Th1)
      recruitment and activation. It is this very recruitment of HIV-susceptible target
      cells that is associated with the initial viral proliferation. Hence, global
      enhancement of the inflammatory response by T-cells and dendritic cells will
      likely feed viral propagation. Mucosal entry sites contain inherent pathways, in
      the form of natural regulatory T-cells (nTreg), that globally dampen the
      inflammatory response. We created a model of this inflammatory response to virus
      as well as inherent nTreg-mediated regulation of Th1 recruitment and activation.
      With simulations using this model we sought to address the net effect of nTreg
      activation and its specific functions as well as identify mechanisms of the
      natural inflammatory response that are best targeted to inhibit viral spread
      without compromising initial antiviral activity. Simulation results provide
      multiple insights that are relevant to developing intervention strategies that
      seek to exploit natural immune processes: (i) induction of the regulatory
      response through nTreg activation expedites viral proliferation due to viral
      production by nTreg itself and not to reduced Natural Killer (NK) cell activity;
      (ii) at the same time, induction of the inflammation response through either DC
      activation or Th1 activation expedites viral proliferation; (iii) within the
      inflammatory pathway, the NK response is an effective controller of viral
      proliferation while DC-mediated stimulation of T-cells is a significant driver of
      viral proliferation; and (iv) nTreg-mediated DC deactivation plays a significant
      role in slowing viral proliferation by inhibiting T-cell stimulation, making this
      function an aide to the antiviral immune response.

PMID- 21871903
TI  - Proteomic analysis to display the effect of low doses of erythropoietin on rat
      liver regeneration.
AB  - AIMS: Several groups found different impact of erythropoietin (EPO) on liver
      regeneration. Both pro-proliferative as well as anti-proliferative and non
      proliferative activities have been reported using high dosage of EPO. Systemic
      administration of high doses of this cytokine is a clinical concern due to risk
      of thrombosis. Herein, we applied EPO in low dosages and investigated whether it
      can stimulate liver regeneration after liver resection. MAIN METHODS: Parameters
      of liver regeneration were assessed 3 days after 70% hepatectomy by means of
      immunochemistry and proteomics. EPO was given twice in low dosages (200 and 600
      IU/kg BW). KEY FINDINGS: We showed that EPO facilitated hepatic regeneration in
      rats. Enhanced hepatocyte proliferation (Ki67, BrdU-positive cells) was observed
      in all EPO-treated groups. By performing Differential Proteomic analysis, we
      identified two proteins which resulted sensitive to EPO treatment after
      hepatectomy: Peroxiredoxin-1 and glutathione S-transferase Mu 1. SIGNIFICANCE:
      Based on our results, low doses of rhEPO increase the hepatic regenerative
      capacity after partial hepatectomy in rats by enhancing hepatocyte proliferation
      and acting on antioxidant enzymes. Both proteins identified by proteomic analysis
      have not previously been associated with liver regeneration and will aid in the
      understanding of EPO's regenerative response having clinical implications to
      treat liver failure.

PMID- 21871904
TI  - Mitochondrial involvement in carbachol-induced intracellular Ca2+ mobilization
      and contraction in rat gastric smooth muscle.
AB  - AIMS: Mitochondria are important modulators of Ca2+ homeostasis. However, it is
      not clear if they modulate and participate in smooth muscle signaling and
      contraction. The aim of the present work was to investigate the role of
      mitochondria in Ca2+ transients and contraction induced by metabotropic
      muscarinic receptor activation in rat gastric smooth muscle. MAIN METHODS:
      Carbachol (CCh)-induced contraction was investigated in the absence or presence
      of increasing concentration of mitochondrial protonophore, carbonyl cyanide p
      (trifluoro-methoxy)phenyl-hydrazone (FCCP), in gastric fundus strips. Ca2+ and
      mitochondrial membrane potential (DeltaPsim) measurements were performed in
      primarily cultured gastric smooth muscle cells loaded with FURA-2 or TMRE dyes.
      KEY FINDINGS: Results show that CCh (1 MUM)-induced contraction was inhibited by
      FCCP in a concentration-dependent manner. In cultured smooth muscle cells CCh (1
      MUM) caused a cytosolic Ca2+ rise. Preincubation with FCCP strongly inhibited CCh
      evoked Ca2+ transients indicating that mitochondria shape intracellular Ca2+
      signals. CCh induced elevations of ?Psim in 60% of the individual mitochondrion
      analyzed. SIGNIFICANCE: Taken together our results indicate that CCh induces
      release of Ca2+ from intracellular stores, which may be modulated by
      mitochondria. Thus, mitochondria participate of the intracellular Ca2+
      homeostasis in muscarinic contraction in gastric fundus smooth muscle.

PMID- 21871905
TI  - Evaluation of urinary biomarkers of oxidative/nitrosative stress in children with
      Down syndrome.
AB  - AIMS: It has been suggested that oxidative stress plays a key role in the
      pathogenesis of Down syndrome (DS). However, urinary biomarkers of oxidative
      stress have been little studied in this condition. Thus, we aimed to assess a set
      of urinary oxidative/nitrosative stress biomarkers in children with DS, with and
      without hypothyroidism, which comprise: 8-hydroxy-2'-deoxyguanosine (8-OHdG),
      isoprostane 15-F(2t)-IsoP, thiobarbituric acid-reacting substances (TBARS),
      advanced glycation end products (AGEs), dityrosine (diTyr), hydrogen peroxide
      (H(2)O(2)) and nitrite/nitrate (NOx). MAIN METHODS: Fluorimetric and
      spectrophotometric assays were performed in children with DS (n=26), some of them
      taking levothyroxine for hypothyroidism (n=7), and their non-Down siblings
      (n=19). KEY FINDINGS: We found that only levels of diTyr were increased in DS,
      although no differences were obtained when hypothyroid DS children were excluded.
      Levels of 8-OHdG, 15-F(2t)-IsoP, TBARS, AGEs, H(2)O(2) and NOx did not differ
      neither between DS and controls nor between hypothyroid DS children and DS
      without hypothyroidism diagnosed. However, diTyr is increased in hypothyroid DS
      children compared with controls. Negative correlations with age were obtained for
      8-OHdG, diTyr and NOx in DS and controls and for 8-OHdG, 15-F(2t)-IsoP, TBARS and
      AGEs in DS. SIGNIFICANCE: Increased oxidative stress in children with DS cannot
      be explained by the urinary levels of 8-OHdG, 15-F(2t)-IsoP, TBARS, AGEs, diTyr,
      H(2)O(2) and NOx, at least with the assays used. Nonetheless, urinary diTyr could
      be used as oxidative/nitrosative stress biomarker in hypothyroid DS children. The
      present work presents evidence of a probable renal impairment in children with DS
      receiving levothyroxine for hypothyroidism.

PMID- 21871906
TI  - Biotin requirements for DNA damage prevention.
AB  - Biotin serves as a covalently bound coenzyme in five human carboxylases; biotin
      is also attached to histones H2A, H3, and H4, although the abundance of
      biotinylated histones is low. Biotinylation of both carboxylases and histones is
      catalyzed by holocarboxylase synthetase. Human biotin requirements are unknown.
      Recommendations for adequate intake of biotin are based on the typical intake of
      biotin in an apparently healthy population, which is only a crude estimate of the
      true intake due to analytical problems. Importantly, intake recommendations do
      not take into account possible effects of biotin deficiency on impairing genome
      stability. Recent studies suggest that biotin deficiency causes de-repression of
      long terminal repeats, thereby causing genome instability. While it was
      originally proposed that these effects are caused by loss of biotinylated
      histones, more recent evidence suggests a more immediate role of holocarboxylase
      synthetase in forming multiprotein complexes in chromatin that are important for
      gene repression. Holocarboxylase synthetase appears to interact physically with
      the methyl-CpG-binding domain protein 2 and, perhaps, histone methyl
      transferases, thereby creating epigenetic synergies between biotinylation and
      methylation events. These observations might offer a mechanistic explanation for
      some of the birth defects seen in biotin-deficient animal models.

PMID- 21871907
TI  - Controlling the spotlight of attention: visual span size and flexibility in
      schizophrenia.
AB  - The current study investigated the size and flexible control of visual span among
      patients with schizophrenia during visual search performance. Visual span is the
      region of the visual field from which one extracts information during a single
      eye fixation, and a larger visual span size is linked to more efficient search
      performance. Therefore, a reduced visual span may explain patients' impaired
      performance on search tasks. The gaze-contingent moving window paradigm was used
      to estimate the visual span size of patients and healthy participants while they
      performed two different search tasks. In addition, changes in visual span size
      were measured as a function of two manipulations of task difficulty: target
      distractor similarity and stimulus familiarity. Patients with schizophrenia
      searched more slowly across both tasks and conditions. Patients also demonstrated
      smaller visual span sizes on the easier search condition in each task. Moreover,
      healthy controls' visual span size increased as target discriminability or
      distractor familiarity increased. This modulation of visual span size, however,
      was reduced or not observed among patients. The implications of the present
      findings, with regard to previously reported visual search deficits, and other
      functional and structural abnormalities associated with schizophrenia, are
      discussed.

PMID- 21871908
TI  - Anxiety profile in morphine-dependent and withdrawn rats: effect of voluntary
      exercise.
AB  - Withdrawal from chronic opiates is associated with an increase in anxiogenic-like
      behaviours, but the anxiety profile in the morphine-dependent animals is not
      clear. Thus, one of the aims of the present study was to examine whether morphine
      dependent rats would increase the expression of anxiogenic-like behaviours in
      novel and stressful conditions. Additionally, recent studies have shown that
      voluntary exercise can reduce anxiety levels in rodents. Therefore, another aim
      of this study was to examine the effect of voluntary exercise on the anxiety
      profile in both morphine-dependent animals and animals experiencing withdrawal.
      Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine
      over a period of 10 days in which they were also allowed voluntary exercise.
      Following these injections, anxiety-like behaviours were tested in the elevated
      plus-maze (EPM) model and the light/dark (L/D) box. We found reductions in time
      spent in, and entries into, the EPM open arms and reductions in time spent in the
      lit side of the L/D box for both sedentary morphine-dependent and withdrawn rats
      as compared to the sedentary control groups. The exercising morphine-dependent
      and withdrawn rats exhibited an increase in EPM open arm time and entries and L/D
      box lit side time as compared with the sedentary control groups. We conclude that
      voluntary exercise decreases the severity of the anxiogenic-like behaviours in
      both morphine-dependent and withdrawn rats. Thus, voluntary exercise could be a
      potential natural method to ameliorate some of the deleterious behavioural
      consequences of opiate abuse.

PMID- 21871909
TI  - Obese adolescents with eating disorders: analysis of metabolic and inflammatory
      states.
AB  - OBJECTIVE: The purpose of the present investigation was to compare the effect of
      interdisciplinary therapy on the physical and metabolic profiles, including body
      composition, insulin resistance and sensitivity as well as adiponectin and leptin
      concentrations, of obese adolescents with and without eating disorder symptoms.
      METHODS: A total of 83 obese adolescents (28 with and 55 without eating disorder
      symptoms) were enrolled for 1 year of interdisciplinary weight-loss therapy
      (clinical, nutritional, exercise, physiotherapy and psychological). Bulimic and
      binge eating symptoms were measured by the Bulimic Investigatory Test, Edinburgh,
      and the Binge Eating Scale, respectively. Leptin and adiponectin concentrations
      were measured with enzyme-linked immunosorbent assay kits. Visceral and
      subcutaneous fat were assessed by ultrasonography. RESULTS: Both groups
      demonstrated improved body mass, body mass index, body fat (%), lean mass,
      visceral fat, subcutaneous fat, homeostasis model assessment insulin-resistance
      index (HOMA-IR), quantitative insulin sensitivity check index, total cholesterol,
      LDL-cholesterol, VLDL, triglycerides, adiponectin and leptin concentrations after
      therapy. We found a positive correlation between leptin concentrations and
      subcutaneous fat in the control group and a negative correlation between
      adiponectin concentrations and HOMA-IR and fat mass (%). The prevalence of obese
      adolescents with eating disorders was reduced by 89% after 1 year of
      interdisciplinary therapy. CONCLUSION: The eating disorder symptoms did not
      impair the metabolic state during weight loss therapy of obese adolescents.
      Additionally, long-term interdisciplinary therapy was effective in reducing the
      chances of developing several co-morbidities in both groups.

PMID- 21871910
TI  - Protective effects of melittin on transforming growth factor-beta1 injury to
      hepatocytes via anti-apoptotic mechanism.
AB  - Melittin is a cationic, hemolytic peptide that is the main toxic component in the
      venom of the honey bee (Apis mellifera). Melittin has multiple effects, including
      anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However,
      the anti-apoptotic mechanisms of melittin have not been fully elucidated in
      hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge
      of the apoptotic mechanisms is important to develop new and effective therapies
      for treatment of cirrhosis, portal hypertension, liver cancer, and other liver
      diseases. In the present study, we investigated the anti-apoptotic effect of
      melittin on transforming growth factor (TGF)-beta1-induced apoptosis in
      hepatocytes. TGF-beta1-treated hepatocytes were exposed to low doses (0.5 and 1
      MUg/mL) and high dose (2 MUg/mL) of melittin. The low doses significantly
      protected these cells from DNA damage in TGF-beta1-induced apoptosis compared to
      the high dose. Also, melittin suppressed TGF-beta1-induced apoptotic activation
      of the Bcl-2 family and caspase family of proteins, which resulted in the
      inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results
      demonstrate that TGF-beta1 induces hepatocyte apoptosis and that an optimal dose
      of melittin exerts anti-apoptotic effects against TGF-beta1-induced injury to
      hepatocytes via the mitochondrial pathway. These results suggest that an optimal
      dose of melittin can serve to protect cells against TGF-beta1-mediated injury.

PMID- 21871911
TI  - Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term
      potentiation in hippocampal CA1 region of the developmental rats.
AB  - Lead (Pb) exposure during development has been associated with impaired long-term
      potentiation (LTP). Hypothyroidism happening upon subjects with occupational
      exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis,
      leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis.
      Hippocampus is one of the targets of Pb exposure, and is sensitive to and
      dependent on thyroid hormones, leading us to explore whether levothyroxine (L
      T(4)) administration could alter the thyroid disequilibrium and impairment of LTP
      in rat hippocampus caused by Pb exposure. Our results show that Pb exposure
      caused a decrease in triiodothyronine (T(3)) and tetraiodothyronine (T(4)) levels
      accompanied by a dramatic decrease of TSH and application of L-T(4) restored
      these changes to about control levels. Hippocampal and blood Pb concentration
      were significantly reduced following L-T(4) treatment. L-T(4) treatment rescued
      the impairment of LTP induced by the Pb exposure. These results suggest that Pb
      exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a
      direct electrophysiological proof that L-T(4) relieves chronic Pb exposure
      induced impairment of synaptic plasticity.

PMID- 21871912
TI  - Degeneration of cortical function in the Royal College of Surgeons rat.
AB  - The purpose of the current study was to determine the progress of cortical
      functional degeneration in the Royal College of Surgeons (RCS) rat. Cortical
      responses were measured with optical imaging of intrinsic signals using gratings
      of various spatial frequencies. Subsequently, electrophysiological recordings
      were also taken across cortical layers in response to a pulse of broad-spectrum
      light. We found significant degeneration in the cortical processing of visual
      information as early as 4 weeks of age. These results show that degeneration in
      the cortical response of the RCS rat starts before development has been properly
      completed.

PMID- 21871913
TI  - Antinociception induced by atorvastatin in different pain models.
AB  - Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A
      (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the
      beneficial effects of statin therapy for primary and secondary prevention of
      cardiovascular disease. It is assumed that the beneficial effects of statin
      therapy are entirely due to cholesterol reduction. Statins have an additional
      activity (pleiotropic effect) that has been associated to their anti-inflammatory
      effects. The aim of the present study was to assess the antinociceptive activity
      of atorvastatin in five animal pain models. The daily administration of 3
      100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent
      antinociception in the writhing, tail-flick, orofacial formalin and formalin hind
      paw tests. However, this antinociceptive activity of atorvastatin was detectable
      only at high concentrations in the hot plate assay. The data obtained in the
      present study demonstrates the effect of atorvastatin to reduce nociception and
      inflammation in different animal pain models.

PMID- 21871914
TI  - Immobilization and stabilization of alpha-galactosidase on Sepabeads EC-EA and EC
      HA.
AB  - alpha-Galactosidase from tomato has been immobilized on Sepabead EC-EA and
      Sepabead EC-HA, which were activated with ethylendiamino and hexamethylenediamino
      groups, respectively. Two strategy was used for the covalent immobilization of
      alpha-galactosidase on the aminated Sepabeads: covalent immobilization of enzyme
      on glutaraldehyde activated support and cross-linking of the adsorbed enzymes on
      to the support with glutaraldehyde. By using these two methods, all the
      immobilized enzymes retained very high activity and the stability of the enzyme
      was also improved. The obtained results showed that, the most stable immobilized
      alpha-galactosidase was obtained with the second strategy. The immobilized
      enzymes were characterized with respect to free counterpart. Some parameters
      effecting to the enzyme activity and stability were also analyzed. The optimum
      temperature and pH were found as 60 degrees C and pH 5.5 for all immobilized
      enzymes, respectively. All the immobilized alpha-galactosidases were more
      thermostable than the free enzyme at 50 degrees C. The stabilities of the
      Sepabead EC-EA and EC-HA adsorbed enzymes treated with glutaraldehyde compared to
      the stability of the free enzyme were a factor of 6 for Sepabead EC-EA and 5.3
      for Sepabead EC-HA. Both the free and immobilized enzymes were very stable
      between pH 3.0 and 6.0 and more than 85% of the initial activities were
      recovered. Under the identical storage conditions the free enzyme lost its
      initial activity more quickly than the immobilized enzymes at the same period of
      time. The immobilized alpha-galactosidase seems to fulfill the requirements for
      different industrial applications.

PMID- 21871915
TI  - Photocrosslinkable biodegradable responsive hydrogels as drug delivery systems.
AB  - Recently, controlled release from biocompatible materials has received much
      attention for biomedical applications. Due to their biocompatibility and
      biodegradability, glucopyranosides such as dextran appear as promising polymeric
      materials if one is able to regulate their rheological properties and the
      encapsulation/release efficiency. In this work graft polymer hydrogels from
      dextran and N-isopropylacrylamide (NIPAAm) were prepared and characterized.
      Dextran molecules were modified with 2-isocyanatoethylmethacrylate (IEMA) in
      order to obtain a polymer with carbon double bonds. Urethane linkages resulted
      from the reaction between hydroxyl groups (OH) of the dextran and isocyanate
      groups (NCO) of the IEMA. The obtained polymer was then crosslinked by UV
      irradiation in the presence of the photoinitiating agent Irgacure 2959 by CIBA.
      The drug Ondansetron was entrapped in the final system and its release profile
      was determined at 25 and 37 degrees C. The characterization of the materials was
      accomplished by: ATR-FTIR (Attenuated Total Reflectance-Fourier Transform
      Infrared) spectroscopy, elemental analysis, lower critical solution temperature
      (LCST) determination, swelling behaviour evaluation, determination of surface
      energy by contact angle measurement and drug delivery profile studies.

PMID- 21871916
TI  - Nano Pd(0) supported on cellulose: a highly efficient and recyclable
      heterogeneous catalyst for the Suzuki coupling and aerobic oxidation of benzyl
      alcohols under liquid phase catalysis.
AB  - Nano palladium(0) supported on cellulose was found to be highly efficient
      recyclable heterogeneous catalyst for the Suzuki coupling between aryl bromides
      and phenyl boronic acid in water and aerobic oxidation of benzyl alcohols using
      air as the source of molecular oxygen in acetonitrile. The Cell-Pd(0) was
      prepared by stirring commercially available cellulose with Pd(OAc)(2) in ethanol
      at 25 degrees C followed by reduction with hydrazine hydrate, leading finally to
      nano Pd(0) particles uniformly distributed on surface of cellulose. This
      catalytic system provides biaryls and polyaryls in excellent yields with very
      high turn over numbers via Suzuki coupling; and benzaldehyde derivatives in high
      yields and selectivity by oxidation in air. Cell-Pd(0) was characterized by X-ray
      diffraction techniques (XRD), thermal analysis (TGA), scanning electron
      microscope (SEM) and transmission electron microscope (TEM).

PMID- 21871917
TI  - Influence of stabilizers cosolutes on catalase conformation.
AB  - The effects of sucrose, mannitol and betaine on the thermodynamic stability and
      the conformational state of the catalase enzyme were analyzed in order to
      understand the molecular mechanism whereby the solutes stabilized the enzyme.
      Catalase was selected as the model enzyme because it is used in several
      biotechnological processes. In the presence of each cosolute, our data have shown
      that there was a significant increase in the thermal stability of catalase. A
      minor stabilization in the enzyme secondary structure were induced by these
      cosolutes, as circular dichroism in the far UV region has demonstrated.
      Furthermore, our results support the idea that the overall native structure of
      catalase becomes more rigid, at least in certain surface areas, in the presence
      of the assayed stabilizers. This last finding can be reasonably explained by the
      exclusion mechanism of cosolutes from the protein surface which increases the
      structured water around this area.

PMID- 21871918
TI  - Toward affective circuit-based preclinical models of depression: sensitizing
      dorsal PAG arousal leads to sustained suppression of positive affect in rats.
AB  - Little is known about why clinical depression feels so bad, perhaps because
      optimal neural circuit-based animal models of depression do not yet exist. Our
      goal here was to develop a strategy of inducing and measuring depressive-like
      states in the rat using neural circuits as both the independent and major
      dependent variables. We hypothesized that repeated electrical stimulation of the
      brain (ESB) within the dorsal periaqueductal gray (dPAG) aversion circuits would
      lead to a long-lasting suppression of 50kHz ultrasonic vocalizations (USVs), a
      validated measure of positive social affect. Fifteen consecutive daily 10min
      sessions of intermittent PAG-ESB reduced systematically evoked 50kHz USVs for up
      to 29 days following termination of ESB treatment, along with altering
      traditional measures of negative affect, including behavioral agitation, sucrose
      intake, and decreased exploratory behavior. These findings suggest a new
      affective circuit-based preclinical model of depression.

PMID- 21871919
TI  - Infectious prion protein alters manganese transport and neurotoxicity in a cell
      culture model of prion disease.
AB  - Protein misfolding and aggregation are considered key features of many
      neurodegenerative diseases, but biochemical mechanisms underlying protein
      misfolding and the propagation of protein aggregates are not well understood.
      Prion disease is a classical neurodegenerative disorder resulting from the
      misfolding of endogenously expressed normal cellular prion protein (PrP(C)).
      Although the exact function of PrP(C) has not been fully elucidated, studies have
      suggested that it can function as a metal binding protein. Interestingly,
      increased brain manganese (Mn) levels have been reported in various prion
      diseases indicating divalent metals also may play a role in the disease process.
      Recently, we reported that PrP(C) protects against Mn-induced cytotoxicity in a
      neural cell culture model. To further understand the role of Mn in prion
      diseases, we examined Mn neurotoxicity in an infectious cell culture model of
      prion disease. Our results show CAD5 scrapie-infected cells were more resistant
      to Mn neurotoxicity as compared to uninfected cells (EC(50)=428.8 MUM for CAD5
      infected cells vs. 211.6 MUM for uninfected cells). Additionally, treatment with
      300 MUM Mn in persistently infected CAD5 cells showed a reduction in
      mitochondrial impairment, caspase-3 activation, and DNA fragmentation when
      compared to uninfected cells. Scrapie-infected cells also showed significantly
      reduced Mn uptake as measured by inductively coupled plasma-mass spectrometry
      (ICP-MS), and altered expression of metal transporting proteins DMT1 and
      transferrin. Together, our data indicate that conversion of PrP to the pathogenic
      isoform enhances its ability to regulate Mn homeostasis, and suggest that
      understanding the interaction of metals with disease-specific proteins may
      provide further insight to protein aggregation in neurodegenerative diseases.

PMID- 21871920
TI  - Role of oxidative stress and the mitochondrial permeability transition in
      methylmercury cytotoxicity.
AB  - Oxidative stress has been implicated in the pathogenesis of methylmercury (MeHg)
      neurotoxicity. Studies of mature neurons suggest that the mitochondrion may be a
      major source of MeHg-induced reactive oxygen species and a critical mediator of
      MeHg-induced neuronal death, likely by activation of apoptotic pathways. It is
      unclear, however, whether the mitochondria of developing and mature neurons are
      equally susceptible to MeHg. Murine embryonal carcinoma (EC) cells, which
      differentiate into neurons following exposure to retinoic acid, were used to
      compare the differentiation-dependent effects of MeHg on ROS production and
      mitochondrial depolarization. EC cells and their neuronal derivatives were pre
      incubated with the ROS indicator 2',7'-dichlorofluoroscein diacetate or
      tetramethylrhodamine methyl ester, an indicator of mitochondrial membrane
      potential, with or without cyclosporin A (CsA), an inhibitor of mitochondrial
      permeability transition pore opening, and examined by laser scanning confocal
      microscopy in the presence of 1.5 MUM MeHg. To examine consequences of
      mitochondrial perturbation, immunohistochemical localization of cytochrome c (cyt
      c) was determined after incubation of cells in MeHg for 4 h. MeHg treatment
      induced earlier and significantly higher levels of ROS production and more
      extensive mitochondrial depolarization in neurons than in undifferentiated EC
      cells. CsA completely inhibited mitochondrial depolarization by MeHg in EC cells
      but only delayed this response in the neurons. In contrast, CsA significantly
      inhibited MeHg-induced neuronal ROS production. Cyt c release was also more
      extensive in neurons, with less protection afforded by CsA. These data indicate
      that neuronal differentiation state influences mitochondrial transition pore
      dynamics and MeHg-stimulated production of ROS.

PMID- 21871921
TI  - Environmental exposure to manganese and motor function of children in Mexico.
AB  - OBJECTIVES: Occupational manganese (Mn) exposure has been associated with motor
      deficits in adult workers, but data on the potential effects of environmental
      exposure to Mn on the developing motor function for a children population is
      scarce. The aim of this study was to evaluate the association between exposure to
      Mn and motor function of school aged children. METHODS: We conducted a cross
      sectional study selecting 195 children (100 exposed and 95 unexposed) between 7
      and 11 years old. The following tests were used to evaluate the motor function:
      Grooved pegboard, finger tapping, and Santa Ana test. Mn exposure was assessed by
      blood (MnB) and hair concentrations (MnH). We constructed linear regression
      models to evaluate the association between exposure to Mn and the different test
      scores adjusting for age, sex, maternal education, hemoglobin and blood lead.
      RESULTS: The median concentration of MnH and MnB was significantly higher in
      exposed (12.6 MUg/g and 9.5 MUg/L) compared to unexposed children (0.6 MUg/g and
      8.0 MUg/L). The exposed children on average performed the grooved pegboard test
      faster, but made more errors, although these results did not reach statistical
      significance with neither one of the Mn exposure biomarkers. MnB showed an
      inverse association on the execution of the finger tapping test (average in 5
      trials beta -0.4, p=0.02), but no association was observed with MnH. CONCLUSIONS:
      A subtle negative association of Mn exposure on motor speed and coordination was
      shown. In adults, the main effect of environmental Mn exposure has been
      associated with motor skills, but these results suggest that such alterations are
      not the main effect on children.

PMID- 21871922
TI  - Preliminary assessment of regular short-term intravenous fluids and antibiotic
      therapy in recurrent UTI.

PMID- 21871923
TI  - An in situ method for the examination of calcium-dependent proteolysis.
AB  - Proteases are involved in a multitude of cellular processes that are critical for
      the maintenance of normal cell function, and their aberrant activity has been
      linked to a large number of diseases. Calcium-dependent proteases (calpains) are
      found in cells distributed throughout the brain, and their activity contributes
      to normal and abnormal brain function. A limitation with common approaches to
      studying the activity of calpain is the requirement for homogenization of tissue
      samples, which limits the ability to resolve the spatial location of protease
      activity, and which also introduces the possibility of interaction with
      endogenous inhibitors that would have otherwise been kept spatially separated in
      vivo. We present a simple method for the investigation of protease activity that
      provides better spatial resolution than alternatives, and that alleviates the
      concern of protein interactions in homogenate. We examined calcium-dependent
      proteolysis in tissue sections by observation of a fluorescence signal produced
      by fragmentation of a casein substrate embedded in an agarose gel solution that
      covered the section. This technique preserved the anatomical characteristics of
      the tissue, and provided spatial resolution sufficient for ready examination of
      protease activity in cells and in blood vessels within a single tissue section.

PMID- 21871924
TI  - Caution in evaluation of removal of virus by filtration: Misinterpretation due to
      detection of viral genome fragments by PCR.
AB  - The testing of biological products at different stages of the manufacturing
      process currently involves quantitative polymerase chain reaction (Q-PCR)-based
      assays. Q-PCR techniques are able to detect not only the viral genome in viral
      particles but also fragments of degraded genome in samples. The ability of 15 and
      19-nm filters to remove viruses was examined by conducting infectivity assays and
      Q-PCR assays using parvovirus B19 (B19), one of the smallest non-enveloped
      viruses. Although the filtered samples showed no infectivity, viral DNA was
      detected by Q-PCR. Interestingly, approximately 90% of the total viral genome in
      15-nm filtrates had a detectable size of less than 0.5kb by the Q-PCR and as a
      consequence reduction factors were underestimated using Q-PCR. The reduction
      factors using Q-PCR might be underestimated due to the presence of a large amount
      of free B19 DNA which shows no infectivity in the tested filtrates. Therefore,
      the results of Q-PCR should be interpreted with caution. The careful design of
      primers is needed to eliminate amplification from fragments of viral DNA by Q
      PCR.

PMID- 21871925
TI  - Sensitive Mie scattering immunoagglutination assay of porcine reproductive and
      respiratory syndrome virus (PRRSV) from lung tissue samples in a microfluidic
      chip.
AB  - A microfluidic immunosensor utilizing Mie scattering immunoaggultination assay
      was developed for rapid and sensitive detection of porcine reproductive and
      respiratory syndrome virus (PRRSV) from lung tissue samples of domesticated pigs.
      Antibodies against PRRSV were conjugated to the surface of highly carboxylated
      polystyrene microparticles (diameter=920nm) and mixed with the diluted PRRSV
      tissue samples in a Y-shaped microchannel. Antibody-antigen binding induced
      microparticle immunoagglutination, which was detected by measuring the forward 45
      degrees  light scattering of 380nm incident beam using microcallipered, proximity
      fiber optics. For comparison, multi-well experiments were also performed using
      the same optical detection setup. The detection limit was determined to be 10(
      3)TCID(50)ml(-1) for PRRSV dissolved in PBS, while those of previous RT-PCR
      studies for PRRSV were 10(1)TCID(50)ml(-1) (conventional assays) or <1TCID(50)ml(
      1) (quantitative real-time assays). Mie scattering simulations were able to
      predict the shape of the PRRSV standard curve, indicating that any non-linearity
      of the standard curve can be interpreted purely as an optical phenomenon. Each
      assay took less than 5min. A strong correlation could be found between RT-PCR and
      this method for the lung tissue samples, even though their respective detection
      mechanisms are different fundamentally (nucleic acids for RT-PCR and virus
      antigens for light scattering immunoagglutination assay). Several different
      dilution factors were also tested for tissue samples, and 1/10 and 1/100 were
      found to be usable. If the microfluidic chips are used only once (i.e. without re
      using them), both superior sensitivity and satisfactory specificity can be
      demonstrated. Specificity studies revealed the presence of Type II PRRSV and non
      presence of Type I PRRSV and that the microfluidic chip assay could detect Type
      II North American strain of PRRSV for the animals tested. This work demonstrates
      the potential of the Mie scattering immunoassay on a microfluidic chip towards
      real-time detection system for viral pathogens in domesticated animals.

PMID- 21871926
TI  - Preliminary evidence of a neurophysiological basis for individual discrimination
      in filial imprinting.
AB  - Filial imprinting involves a predisposition for biologically important stimuli
      and a learning process directing preferences towards a particular stimulus.
      Learning underlies discrimination between imprinted and unfamiliar individuals
      and depends upon the IMM (intermediate and medial mesopallium). Here, IMM neurons
      responded differentially to familiar and unfamiliar conspecifics following
      socialization and the neurophysiological effects of social experience differed
      between hemispheres. Such findings may provide a neurophysiological basis for
      individual discrimination in imprinting.

PMID- 21871927
TI  - Cholecystokinin impact on rainbow trout glucose homeostasis: possible involvement
      of central glucosensors.
AB  - Although the role of cholecystokinin (CCK) on fish appetite regulation has been
      widely studied, its involvement in the regulation of glucose metabolism had been
      little explored to date. In the present study we have carried out different
      experimental approaches to study CCK effects in rainbow trout (a so-called
      'glucose intolerant' fish species) glucose homeostasis. We have found that for
      the first time in a vertebrate species, systemic or central CCK administration
      causes hyperglycemia, which is at least in part related to the presence of an
      ancestral gut-brain axis in which CCK is involved. By using capsaicin we have
      found that part of the action of CCK on glucose homeostasis is mediated by vagal
      and splanchnic afferents. Changes in hepatic metabolism after systemic CCK
      administration suggest that the effects are not directly taking place on the
      liver, but probably in other tissues, while after the central CCK administration,
      the glycogenolytic response observed in liver could be mediated by the activation
      of the sympathetic system. In hypothalamus and hindbrain changes elicited by CCK
      8 treatment are likely related to the glucosensor response to the increased
      glycemia and/or vagal/splanchnic afferences whereas in hindbrain a possible
      action through specific CCK-1 receptors cannot be excluded. All these processes
      result in changes in metabolic parameters related with glucose homeostasis
      control. Further studies are needed to fully understand the role of this peptide
      on glucose homeostasis control in fish.

PMID- 21871928
TI  - Urotensin-II-stimulated expression of pro-angiogenic factors in human vascular
      endothelial cells.
AB  - Urotensin-II (U-II) is an endogenous peptide recently characterized as a
      "nonclassic" pro-angiogenic cytokine. In fact, human vascular endothelial cells
      express the U-II receptor and exhibit a strong in vitro angiogenic response to
      the peptide, which was specifically triggered by the binding of U-II to its
      receptor and involved the activation of ERK1/2 and PI3K/Akt signaling pathways.
      Moreover, available studies, designed to investigate the pro-angiogenic effect
      quite shortly following U-II stimulation, suggested that the angiogenic action of
      the peptide was direct and not associated with an increased expression of
      vascular endothelial growth factor (VEGF) and/or its receptors. In the present
      study, the expression of three pro-angiogenic factors, namely VEGF, endothelin-1,
      and adrenomedullin, was studied in human umbilical vein endothelial cells (HUVEC)
      for longer times of U-II stimulation. RT-PCR and Western blot indicated that in
      HUVEC, exposed for at least 24h to U-II, the expression of the three angiogenic
      molecules was significantly increased at both mRNA and protein level, opening the
      possibility that U-II, not only could exert a direct stimulation of an angiogenic
      phenotype in endothelial cells quite shortly following exposure to the peptide,
      but could also further enhance the process indirectly by inducing in the cells a
      delayed production of other pro-angiogenic factors. Interestingly, a preliminary
      analysis of the time course of the in vitro capillary-like pattern formation was
      consistent with this view, suggesting a two phase temporal dynamics of the
      process.

PMID- 21871929
TI  - Whole genome sequencing of environmental Vibrio cholerae O1 from 10 nanograms of
      DNA using short reads.
AB  - Multiple Displacement Amplification (MDA) of DNA using phi29 (phi29) DNA
      polymerase amplifies DNA several billion-fold, which has proved to be potentially
      very useful for evaluating genome information in a culture-independent manner.
      Whole genome sequencing using DNA from a single prokaryotic genome copy amplified
      by MDA has not yet been achieved due to the formation of chimeras and skewed
      amplification of genomic regions during the MDA step, which then precludes genome
      assembly. We have hereby addressed the issue by using 10 ng of genomic Vibrio
      cholerae DNA extracted within an agarose plug to ensure circularity as a starting
      point for MDA and then sequencing the amplified yield using the SOLiD platform.
      We successfully managed to assemble the entire genome of V. cholerae strain
      LMA3984-4 (environmental O1 strain isolated in urban Amazonia) using a hybrid de
      novo assembly strategy. Using our method, only 178 out of 16,713 (1%) of contigs
      were not able to be inserted into either chromosome scaffold, and out of these
      178, only 3 appeared to be chimeras. The other contigs seem to be the result of
      template-independent non-specific amplification during MDA, yielding spurious
      reads. Extraction of genomic DNA within an agarose plug in order to ensure
      circularity of the extracted genome might be key to minimizing amplification bias
      by MDA for WGS.

PMID- 21871930
TI  - Construction of a conditional lethal Salmonella mutant via genetic recombination
      using the ara system and asd gene.
AB  - In order to construct a conditional lethal Salmonella mutant, an arabinose
      regulated recombinant genetic system was used. The Salmonella aspartate
      semialdehyde dehydrogenase (asd) gene was localized under the control of araC
      P(araBAD) in a plasmid to create the araC P(araBAD)::asd cassette. The cassette
      was cloned into a plasmid carrying a p15A replication origin to create the
      recombinant plasmid pMMP55. The growth of Salmonella MMP10 harboring pMMP55 was
      dependent on the presence of arabinose. In the presence of arabinose, the Asd
      deficiency due to chromosomal deletion of asd in the Salmonella host was
      complemented by the asd gene transcribed and translated under the P(araBAD)
      promoter and araBAD Shine-Dalgarno (SD) sequence in pMMP55. Growth inhibition of
      the strain was demonstrated by arabinose depletion in M9 minimal medium,
      indicating that the strain were unable to grow in an arabinose-limited
      environment. In addition, the analysis of a 50% lethal dose (LD50) using mice
      revealed that the strain MMP10 exhibited attenuation by approximately 100-fold
      relative to that of the unmodified strain. In conclusion, these data suggest that
      the araC P(araBAD)::asd system developed in this study can be used to construct
      conditional lethal Salmonella mutants for application as safe, live-attenuated
      Salmonella vaccines.

PMID- 21871932
TI  - The involvement of P2X1 receptor in pyramidal cell degeneration in the rat
      hippocampus after trimethyltin administration.
AB  - The P2 family of receptors for adenosine 5'-triphosphate (ATP) is involved in
      several neuronal and glial cell functions in the central nervous system (CNS),
      and impaired function of these receptors is associated with both neuronal and
      glial dysfunction. Using quantitative reverse-transcription polymerase chain
      reaction (qRT-PCR) and immunohistochemical analysis, we examined the expression
      profiles of P2 subtype receptors in the rat hippocampus following treatment with
      the neurotoxicant trimethyltin (TMT). Among the subtypes, P2X1 exhibited a unique
      profile, with an increase in expression prior to the onset of cell death after
      TMT administration, and a gradual decrease thereafter in neuronal cells in the
      rat hippocampus. This expression pattern was similar to that of cyclooxygenase-2
      (COX-2) following TMT administration. The P2X1 antagonist NF499 strongly
      prevented neuronal cell death induced by TMT in the CA1 region, and successfully
      suppressed locomotor hyperreactivity. Furthermore, NF449 administration also
      inhibited COX-2 expression in the CA1 region on day 3 following TMT treatment,
      whereas no change was observed in the CA3. These findings suggest that P2X1 plays
      a primary role in TMT-induced neuronal cell death in the CA1 region.

PMID- 21871931
TI  - Heart rate reactivity is associated with future cognitive ability and cognitive
      change in a large community sample.
AB  - The relationship between cardiovascular reactions to acute mental challenge in
      the laboratory and cognitive ability has received scant attention. The present
      study examined the association between reactivity and future cognitive ability.
      Heart rate and blood pressure reactions to a mental stress task were measured in
      1647 participants comprising three distinct age cohorts. Cognitive ability was
      assessed using the Alice Heim-4 test of general intelligence and choice reaction
      time 5 and 12 years later. High heart rate reactivity was related to higher
      general intelligence scores and faster choice reaction times at both follow-ups.
      High heart rate reactivity was also associated with a smaller decline in
      cognitive ability between assessments. These associations were still evident
      following adjustment for a wide range of potentially confounding variables. The
      present results are consistent with the notion that high reactivity may not
      always be a maladaptive response and that low or blunted reactivity may also have
      negative corollaries.

PMID- 21871933
TI  - Surface modification of wool with protease extracted polypeptides.
AB  - Polypeptides were extracted from wool protein fibres using the serine type
      protease Esperase 8.0L (EC 3.4.21.62), a subtilisin from Bacillus sp., in a
      reducing solution. The extracted polypeptides, in aqueous liquor, were then
      applied to modify the fibre surface of wool fabric with or without additional
      protease. The treated wool fabric was subsequently treated with the cross-linking
      agent, glycerol diglycidyl ether, and then underwent a curing process to affix
      the polypeptide to the fibre. The resulting knitted fabric showed a very high
      level of shrink-resistance to machine washing, without excessive fibre damage.
      Shrinkage of 1-2% could be achieved after 5 times 5A washes with minimal (<1%)
      weight loss due to washing and a burst strength of 317 kPa.

PMID- 21871934
TI  - High-temperature cultivation and 5' mRNA optimization are key factors for the
      efficient overexpression of thermostable Deinococcus geothermalis purine
      nucleoside phosphorylase in Escherichia coli.
AB  - Overexpression of genes from thermophiles in Escherichia coli is an attractive
      approach towards the large-scale production of thermostable biocatalysts.
      However, various factors can challenge efficient heterologous protein expression-
      one example is the formation of stable 5' mRNA secondary structures that can
      impede an efficient translation initiation. In this work, we describe the
      expression optimization of purine nucleoside phosphorylase from the thermophilic
      microbe Deinococcus geothermalis in E. coli. Poor expression levels caused by
      stable secondary 5' mRNA structure formation were addressed by two different
      approaches: (i) increasing the cultivation temperature above the range used
      typically for recombinant protein expression and (ii) optimizing the 5' mRNA
      sequence for reduced secondary structures in the translation initiation region.
      The increase of the cultivation temperature from 30 degrees C to 42 degrees C
      allowed a more than 10-fold increase of activity per cell and optimizing the 5'
      mRNA gene sequence further increased the activity per cell 1.7-fold at 42 degrees
      C. Thus, the combination of high-temperature cultivation and 5' sequence
      optimization is described as an effective approach to overcome poor expression
      levels resulting from stable secondary 5' mRNA structure formation. We suggest
      that this method is especially suitable for improving the expression of proteins
      derived from thermophiles in E. coli.

PMID- 21871935
TI  - Intracerebroventricular administration of neuronostatin induces depression-like
      effect in forced swim test of mice.
AB  - Neuronostatin is a recently discovered endogenous bioactive peptide that is
      encoded by pro-mRNA of somatostatin. In the present study, we investigated the
      effect of neuronostatin on mood regulation in the forced swim test of mice. Our
      results showed intracerebroventricular (i.c.v.) administration of neuronostatin
      produced an increase in the immobility time, suggesting that neuronostatin
      induced depression-like effect. In order to rule out the possibility that
      neuronostatin had increased immobility time by a non-specific reduction in
      general activity, the effect of neuronostatin on locomotor activity was examined.
      Neuronostatin had no influence on locomotor activity in mice. In addition, the
      depression-like effect of neuronostatin was completely reversed by melanocortin
      3/4 receptor antagonist SHU9119 or GABAA receptor antagonist bicuculline, but not
      by opioid receptor antagonist naloxone. These data suggested that the depression
      like effect induced by i.c.v. administered neuronostatin was dependent upon the
      central melanocortin system and GABAA receptor. In conclusion, the results of
      this study report that neuronostatin induces depression-like effect. These
      findings reveal that neuronostatin is a new neuropeptide with an important role
      in regulating depressive behavior.

PMID- 21871936
TI  - Alterations in protein and gene expression within the barrel cortices of ZnT3
      knockout mice: experience-independent and dependent changes.
AB  - Much evidence exists for the involvement of vesicular zinc in neurotransmission
      and cortical plasticity. Recent studies have reported that mice deficient in zinc
      transporter-3 protein (ZnT3) and thus, vesicular zinc, have significant
      behavioural and biochemical deficits. Here, we examined whether phenotypic
      differences existed in the barrel cortices of ZnT3 KO mice using functional
      proteomics and quantitative PCR. Additionally, by manipulating whisker input, we
      also investigated experience-dependent changes in protein and gene expression,
      thereby assaying how cortical plasticity is different in the absence of vesicular
      zinc. The GABA metabolizing protein ABAT was observed in lower abundances
      consistently in KO mice. Several presynaptic proteins were identified that were
      abundant in differing amounts between the WT and KO groups in an experience
      dependent manner. At baseline, we observed a decrease in the relative expression
      of Dlg4, Grin2a, Mt3, and Ntrkb genes in KO mice. The reduced expression of Nrtkb
      persisted with whisker plucking. These data demonstrate that fundamental changes
      in the expression of proteins and genes important in neurotransmission occur in
      the absence of vesicular zinc. Furthermore, the complement of experience
      dependent changes were different between WT and KO mice, indicating that the lack
      of vesicular zinc affects the process of cortical plasticity.

PMID- 21871937
TI  - The role of interleukin DNA polymorphisms in gastric cancer.
AB  - Gastric carcinoma is one of the most widespread malignancies worldwide.
      Interleukins are the key group of cytokines which may have tumor-promoting or
      tumor-suppressing effect, and receptors for them, of course, have the same
      importance in this context. However, mechanisms of their impact on tumor are not
      fully understood up to date. Numerous studies provide conflicting data, that
      makes picture more confusing and complicated. It is known that single nucleotide
      polymorphisms in interleukin genes may dramatically affect on protein expression
      level, or alter its functions, which may lead to gastritis or ulcer, and
      eventually promote cancer occurrence. Furthermore, some of these genetic
      polymorphisms may serve as predictive factors for cancer prognosis and
      prevention. In order to understand the impact of each genetic polymorphism, the
      review of IL-1B, IL-4, IL-6, IL-8, IL-10, IL17A, IL-17F DNA polymorphisms on
      gastric carcinoma was done, and risk alleles were recommended for further
      research.

PMID- 21871938
TI  - Does high-resolution donor typing of HLA-C or other loci upon registration confer
      advantages to patients?
AB  - Our study compared all requests for confirmatory typing (CT requests) received in
      our center between May 2007 and December 2009 (n = 134) for donors issued from 3
      groups defined by different human leukocyte antigen (HLA) loci typed at different
      levels of resolution. We observed a significant advantage for volunteers when HLA
      C 2-digit typing was available or with HLA-A, -B, -C, -DRB1 4-digit typing
      compared with generic HLA-A, -B, -DRB1, -DQB1 DNA typing: increased percentage of
      CT requests (p < 0.001), increased rate of donor selection for donation (p <
      0.001), and decreased time frame for donor search (p = 0.025). The time frame for
      a successful search (donation) is similar among the 3 groups, indicating that the
      search might be concluded more rapidly when the pathology is clinically active or
      when the patient is at a high risk of relapse (76% of our cases) or for pediatric
      patients (24% of our cases), regardless of HLA typing resolution. Improvement of
      HLA typing for volunteers could be a great advantage for first selection in the
      absence of emergency or high-risk disease. Knowledge of HLA-C should be used to
      prioritize the selection of donors for further testing and could allow a better
      donor selection process, reducing search duration and increasing efficiency. In
      most cases, 2-digit typing for HLA-C associated with specific tools to estimate
      the probability of finding a matched donor could be sufficient.

PMID- 21871939
TI  - In-depth process understanding of RECOMBIVAX HB(r) maturation and potential
      epitope improvements with redox treatment: multifaceted biochemical and
      immunochemical characterization.
AB  - Recombinant Hepatitis B surface antigen virus-like particles (VLPs) produced in
      yeast undergo spontaneous maturation during the vaccine production process, and
      the biophysical characteristics of the particles with respect to maturation were
      described in Zhao et al. (2006) [13]. Here we report additional biochemical and
      immunochemical characterization by various techniques, including the use of a
      panel of monoclonal antibodies (mAbs) that differ in their selectivity and
      conformation-sensitivity, for probing surface epitope structures. Crosslinking
      via interchain disulfide formation and binding of conformational specific
      antibodies in the mature particles were shown to be progressively enhanced. We
      show that redox-mediated VLP maturation is superior to heat-induced maturation in
      terms of generating VLPs which exhibit more complete crosslinking (>95%) and 2-
      to 3-fold higher antigenicity as defined by conformational antibodies. Therefore,
      the resulting VLPs from redox treatment resemble more closely their plasma
      derived counterparts. The value of using multiple mAbs for probing surface
      epitopes was clearly demonstrated as different mAbs showed different degrees of
      sensitivity to the structural changes during HBsAg VLP maturation. The rapid,
      label-free technology of surface plasmon resonance performed at a single antigen
      concentration was shown to correlate well with a sandwich ELISA using parallel
      line analysis, currently implemented for product release and stability testing of
      RECOMBIVAX HB((r)). Surface plasmon resonance offers both convenience and
      flexibility; multiple mAbs can be tested one at a time in the same set of
      experiments, providing a means to assess changes to individual epitopes. Taken
      together, these quantitative analytical tools enable more rapid, in-depth, and
      comprehensive process monitoring, process optimization, and assessment of product
      consistency and stability.

PMID- 21871940
TI  - Aluminium-based adjuvants should not be used as placebos in clinical trials.

PMID- 21871941
TI  - Structural modification effects on bioactivities of the novel 15-mer peptide
      adjuvant.
AB  - Structure-function relationship studies for novel GMDP-peptide mimic,
      RVPPRYHAKISPMVN (RN-peptide) were performed on array of truncated and 'Ala-scan'
      analogues. The shortest peptide fragment possessing detectable affinity towards
      anti-GMDP-antibodies was demonstrated to be PRYH. RN-peptide analogues lacking up
      to 8 residues at C-terminus were found to retain adjuvant activity with the
      minimal active peptide being RVPPRYH. Evaluation of Ala-scan analogues
      highlighted that adjuvant activity is most critically dependent on both arginine
      residues, but also is sensitive to substitution of K9, I10, S11 and M13 amino
      acid residues, the functional importance of which was additionally confirmed by
      testing peptides truncated at both termini.

PMID- 21871942
TI  - Degradation of transgene DNA in genetically modified herbicide-tolerant rice
      during food processing.
AB  - In order to assess the effect of food processing on the degradation of exogenous
      DNA components in sweet rice wine and rice crackers made from genetically
      modified (GM) rice (Oryza sativa L.), we developed genomic DNA extraction methods
      and compared the effect of different food processing procedures on DNA
      degradation. It was found that the purity, quantity and quality of DNA by
      alkaline lysis method were higher than by CTAB (cetyltrimethylammonium bromide)
      method. For sweet rice wine, CAMV35S (cauliflower mosaic virus 35S) promoter and
      NOS (nopaline synthase) terminator were degraded by the third day, whereas the
      exogenous gene Bar (bialaphos resistance) remained unaffected. For rice crackers,
      boiling, drying and microwaving contributed to the initial degradations of DNA.
      Baking resulted in further degradations, and frying led to the most severe
      changes. These results indicated that the stability of DNA in GM rice was
      different under different processing conditions. For sweet rice wine, Bar was
      most stable, followed by NOS, CAMV35S, and SPS. For rice crackers, CAMV35S was
      most stable, followed by SPS, NOS, and Bar.

PMID- 21871943
TI  - Inter- and intra-laboratory study to determine the reproducibility of
      toxicogenomics datasets.
AB  - The application of toxicogenomics as a predictive tool for chemical risk
      assessment has been under evaluation by the toxicology community for more than a
      decade. However, it predominately remains a tool for investigative research
      rather than for regulatory risk assessment. In this study, we assessed whether
      the current generation of microarray technology in combination with an in vitro
      experimental design was capable of generating robust, reproducible data of
      sufficient quality to show promise as a tool for regulatory risk assessment. To
      this end, we designed a prospective collaborative study to determine the level of
      inter- and intra-laboratory reproducibility between three independent
      laboratories. All test centres (TCs) adopted the same protocols for all aspects
      of the toxicogenomic experiment including cell culture, chemical exposure, RNA
      extraction, microarray data generation and analysis. As a case study, the
      genotoxic carcinogen benzo[a]pyrene (B[a]P) and the human hepatoma cell line
      HepG2 were used to generate three comparable toxicogenomic data sets. High levels
      of technical reproducibility were demonstrated using a widely employed gene
      expression microarray platform. While differences at the global transcriptome
      level were observed between the TCs, a common subset of B[a]P responsive genes
      (n=400 gene probes) was identified at all TCs which included many genes
      previously reported in the literature as B[a]P responsive. These data show
      promise that the current generation of microarray technology, in combination with
      a standard in vitro experimental design, can produce robust data that can be
      generated reproducibly in independent laboratories. Future work will need to
      determine whether such reproducible in vitro model(s) can be predictive for a
      range of toxic chemicals with different mechanisms of action and thus be
      considered as part of future testing regimes for regulatory risk assessment.

PMID- 21871944
TI  - Enantioselective endocrine-disrupting effects of bifenthrin on hormone synthesis
      in rat ovarian cells.
AB  - Bifenthrin (BF), a broad-spectrum and widely used synthetic pyrethroid, is a
      typical chiral pesticide. More attention is being paid to the health risk
      assessment of the enantioselective toxicity of BF isomers. In this study, we used
      rat ovarian granulosa cells as in vitro model to investigate effects of BF
      enantiomers on the biosynthesis of two hormones, progesterone and prostaglandin
      E2 (PGE2), which are critical for mammalian reproduction. We showed that 1S-cis
      BF, but not 1R-cis-BF significantly decreased the secretion of progesterone and
      PGE2 in granulosa cells. 1S-isomer of BF reduced the expression of genes P450scc,
      StAR, PBR and DBI, as well as COX-2, which are involved in regulating the rate
      limiting steps of progesterone or PGE2 biosynthesis. The transcriptional
      activation of StAR and COX-2 promoter were disrupted by 1S-cis-BF. Furthermore,
      activity of protein kinase C (PKC), an important signaling mediator of
      progesterone and PGE2 synthesis, was differentially inhibited by 1S-cis-BF. The
      data of molecular docking revealed that one hydrogen bond was formed between 1S
      cis-BF and PKC protein. In conclusion, we firstly reported in this study the
      enantioselective disrupting effects of BF isomers on progesterone and PGE2
      synthesis via PKC pathway in rat ovarian cells. Our findings suggest that the
      enantioselective toxicity of chiral pesticides should be considered for
      evaluating mammalian reproductive health, a toxicologic endpoint of great concern
      in health risk assessment.

PMID- 21871945
TI  - Induction of glutathione synthesis and conjugation by 3,4
      methylenedioxymethamphetamine (MDMA) and 3,4-dihydroxymethamphetamine (HHMA) in
      human and rat liver cells, including the protective role of some antioxidants.
AB  - MDMA (3,4-methylenedioxymethamphetamine) metabolism is a major cause of MDMA
      mediated hepatotoxicity. In this study the effects of MDMA and its metabolites on
      the glutathione system were evaluated. Glutathione (GSH/GSSG) levels and gene
      expression of glutamate cysteine ligase catalytic subunit (GCLC), glutathione-S
      transferase (GST) and pregnane X receptor (PXR) were compared in the immortalized
      human liver epithelial cell line THLE-Neo lacking phase I metabolism and primary
      rat hepatocytes expressing both phase I and II metabolism. Furthermore, we
      evaluated the potential protective effects of two antioxidants, N-acetyl-cysteine
      (NAC) and sulforaphane (SFN) in these cell systems. In THLE-Neo cells, the MDMA
      metabolite 3,4-dihydroxymetamphetamine (HHMA) significantly decreased cell
      viability and depleted GSH levels, resulting in an increased expression of GCLC
      and GST up to 3.4- and 2.2-fold, respectively. In primary rat hepatocytes, cell
      viability or GSH levels were not significantly affected upon MDMA exposure. GCLC
      expression levels where not significantly altered either, although GST expression
      was increased 2.3-fold. NAC counteracted MDMA-induced cytotoxicity and restored
      GSH levels. Phase II enzyme expression was also reverted. Conversely, SFN
      increased MDMA-induced cytotoxicity and GSH depletion, while GCLC and GST
      expression were significantly induced. In addition, PXR expression decreased
      after HHMA and MDMA exposure, while co-exposure to SFN induced it up to 3.6- and
      3.9-fold compared to vehicle-control in the THLE-Neo cells and rat hepatocytes,
      respectively. Taken together, these data indicate that HHMA is a major factor in
      the MDMA-mediated hepatotoxicity through interaction with the glutathione system.
      The results of our study show that for MDMA intoxication the treatment with an
      antioxidant such as NAC may counteract the potentially hepatotoxicity. However,
      SFN supplementation should be considered with care because of the indications of
      possible drug-drug interactions.

PMID- 21871946
TI  - Antitumor effects and cell selectivity of temporin-1CEa, an antimicrobial peptide
      from the skin secretions of the Chinese brown frog (Rana chensinensis).
AB  - Many antimicrobial peptides from amphibian exhibit additional anticancer
      properties due to a similar mechanism of action at both bacterial and cancer
      cells. We have previously reported the cDNA sequence of the antimicrobial peptide
      temporin-1CEa precursor cloned from the Chinese brown frog Rana chensinensis. In
      this study, we purified, synthesized and structurally characterized temporin-1CEa
      from the skin secretions of R. chensinensis. The cytotoxicity and cell
      selectivity of temporin-1CEa were further examined on twelve human carcinoma cell
      lines and on normal human umbilical vein smooth muscle cells (HUVSMCs). Our
      results indicated that temporin-1CEa has the amino acid sequence of
      FVDLKKIANIINSIF-NH(2), and exhibits 50-56% identity with temporin family peptides
      from other frog species. The CD spectra for temporin-1CEa adopted a well-defined
      alpha-helical structure in 50% TFE/water solution. The results of MTT assay
      showed that temporin-1CEa exhibits cytotoxicity to all tested cancer cell lines
      in a concentration-dependent manner, being MCF-7 cells the most sensitive.
      Moreover, temporin-1CEa had lower hemolytic effect to human erythrocytes and had
      no significant cytotoxicity to normal HUVSMCs at concentrations showed potent
      antitumor activity. In summary, temporin-1CEa, an amphiphilic alpha-helical
      cationic peptide, may represent a novel anticancer agent for breast cancer
      therapy, considering its cancer cell selectivity and relatively lower
      cytotoxicity to normal cells.

PMID- 21871947
TI  - Nonlinear response of gene expression to chemical perturbations: a noise-detector
      model and its predictions.
AB  - The widespread use of microarrays provided a first glimpse at some simple laws
      and organizing principles that govern the transcriptome. Previous analyses have
      shown that the transcriptional organization is very heterogeneous and
      characterized by a power-law decay for gene expression levels. Moreover, a simple
      law was unveiled suggesting that gene expression dynamic changes under stress are
      proportional to their initial expression values. However, to elucidate and assess
      the underlying governing principles of transcriptional organization, we do not
      only need to identify them, but also provide theoretical models that are able to
      faithfully capture and reproduce them. Here we present a method to investigate
      the gene expression dynamics inspired by the theory of nonlinear transformation
      of random signals and noise. The model is able to explain not only the well-known
      power-law decay for abundance of expression levels, but also to reproduce the
      linear dependence of the standard deviation of gene expression change with
      respect to the initial expression value (also known as rich-travels-more
      dynamics). To our knowledge, this is the first model applied to gene expression
      dynamics that is able to simultaneously predict both statistical features. The
      theoretical framework derives an indicator to measure the coupling between gene
      expression and specific perturbations. Using genome-wide transcriptional data,
      this indicator identifies genes strongly coupled to specific inflammatory
      responses to different pathogens. The novel application of signal and noise
      theory to study intracellular responses and gene expression changes offers not
      only a new theoretical avenue to study transcriptional responses to environmental
      stresses and chemical signals but also provides predictive capability at the
      genome scale.

PMID- 21871948
TI  - Circadian clock signals in the adrenal cortex.
AB  - Circadian secretion of steroid hormones by the adrenal cortex is required to
      maintain whole body homeostasis and to adequately respond to or anticipate
      environmental changes. The richly vascularized zona glomerulosa (ZG) cells in the
      pericapsular region regulate osmotic balance of body fluid by secreting
      mineralocorticoids responding to circulating bioactive substances, and more
      medially located zona fasciculata (ZF) cells regulate energy supply and
      consumption by secreting glucocorticoids under neuronal and hormonal regulation.
      The circadian clock regulates both steroidogenic pathways: the clock within the
      ZG regulates mineralocorticoid production via controlling rate-limiting synthetic
      enzymes, and the ZF secretes glucocorticoid hormones into the systemic
      circulation under the control of central clock in the suprachiasmatic nucleus. A
      functional biological clock at the systemic and cellular levels is therefore
      necessary for steroid synthesis and secretion.

PMID- 21871949
TI  - Anatomical relations between neuropeptide Y, galanin, and gonadotropin-releasing
      hormone in the brain of chondrostean, the Siberian sturgeon Acipenser baeri.
AB  - We investigated the immunohistochemical localization of immunoreactive (ir) cell
      bodies and fibers of neuropeptide Y (NPY) and galanin (GAL), and the anatomical
      relations between these neurons in the brain of the Siberian sturgeon Acipenser
      baeri to clarify the interactions between these neuropeptides. Furthermore, the
      anatomic relations between NPY and gonadotropin-releasing hormone (GnRH) in the
      brain were also examined. NPY-ir cell bodies were observed in the ventral part of
      the ventral telencephalon (Vv). NPY-ir fibers were observed throughout the brain,
      primarily in the ventral telencephalon, hypothalamus, optic tectum, and midbrain.
      GAL-ir cell bodies were observed in the Vv, nucleus anterioris tuberis (NAT),
      nucleus lateralis tuberis (NLT), and nucleus recessus posterioris (NRP). GAL-ir
      fibers were also observed throughout the brain. Neither NPY-ir fibers nor GAL-ir
      fibers were detected in the pituitary. Dual-label immunohistochemistry revealed
      that some GAL-ir fibers were in close contact with NPY-ir cell bodies in the Vv,
      and some NPY-ir fibers were in close contact with GAL-ir cell bodies in the NAT.
      Furthermore, some NPY-ir fibers were in close contact with GnRH-ir cell bodies in
      the preoptic area, and some GnRH-ir fibers were in close contact with NPY-ir cell
      bodies in the Vv. These findings suggest that reciprocal connections exist
      between the NPY and GAL neurons and between the NPY and GnRH neurons in the brain
      of the Siberian sturgeon.

PMID- 21871950
TI  - Proportional neuronal loss between the primary motor and sensory cortex in
      amyotrophic lateral sclerosis.
AB  - The number of neurons in the primary motor cortex (MI) and the primary
      somatosensory cortex (SI) were estimated in the same locations of brains from
      sporadic amyotrophic lateral sclerosis (ALS) cases and controls. The number of MI
      and SI neurons and Betz cells were significantly decreased in the ALS cases as
      compared to the controls. The number of neurons in MI and SI was independent of
      age at death or duration of disease. Moreover, the number of neurons in MI and SI
      was significantly correlated, suggesting that the neurons in both sites might be
      interdependent and might decrease proportionally.

PMID- 21871951
TI  - Deciding when to "cash in" when outcomes are continuously improving: an
      escalating interest task.
AB  - A first-person shooter video game was adapted for the study of choice between
      smaller sooner and larger later outcomes. Participants chose when to fire a
      weapon that increased in damage potential over a 10s interval, an escalating
      interest situation. Across two experiments, participants demonstrated sensitivity
      to the nature of the mathematical function that defined the relationship between
      waiting and damage potential. In Experiment 1, people tended to wait longer when
      doing so allowed them to eliminate targets more quickly. In Experiment 2, people
      tended to wait longer to increase the probability of a constant magnitude outcome
      than to increase the magnitude of a 100% certain outcome that was matched for the
      same expected value (i.e., probability times magnitude). The two experiments
      demonstrated sensitivity to the way in which an outcome improves when the outcome
      is continuously available. The results also demonstrate that this new video game
      task is useful for generating sensitivity to delay to reinforcement over time
      scales that are typically used in nonhuman animal studies.

PMID- 21871952
TI  - Order effects after blocked preexposure to two compound flavors.
AB  - In the first three experiments two groups of rats received prolonged blocked
      preexposure to AX-BX or to BX-AX. Experiment 1 showed that conditioning of AX
      after preexposure resulted in less generalization to BX in the AX-BX group than
      in the BX-AX group. Experiments 2 and 3 constituted, respectively, retardation
      and summation tests of the inhibitory properties acquired by B after preexposure
      and conditioning of A. Excitatory conditioning of B was retarded in the AX-BX
      group (Experiment 2) and only in this group B was able to alleviate the aversion
      conditioned to a new stimulus (Experiment 3). These results are explained as a
      consequence of the formation, in the AX-BX group, of inhibitory associations
      directed from B to A. A fourth experiment provided evidence that the A<->X
      association was preserved until the end of the preexposure phase in this group,
      which is a requisite for the formation of these inhibitory associations.

PMID- 21871953
TI  - Congener-specific action of PBDEs on steroid secretion, CYP17, 17beta-HSD and
      CYP19 activity and protein expression in porcine ovarian follicles.
AB  - The available data on reproductive toxicity of PBDEs are limited. In the present
      study we evaluated the direct effects of BDE-47, -99 and -100 on porcine ovarian
      follicular steroid secretions and the activity and expression of enzymes involved
      in its synthesis. Follicles were exposed to BDE-47 (0.5, 25 and 50 ng/ml), BDE-99
      (0.25, 10 and 17.5 ng/ml), or BDE-100 (0.1, 4 and 12.5 ng/ml) for 24h.
      Progesterone (P4), androstenedione (A4), testosterone (T) and estradiol (E2)
      levels in the media were determined by EIA. CYP17, 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) and CYP19 activity was measured by conversion of
      P4>A4, A4>T and T to E2, respectively. Protein expression of CYP17, 17beta-HSD
      and CYP19 was measured by western blot. All of the congeners explored in this
      study increase testosterone secretion. However, in the case of BDE-47 due to
      activation of 17 beta-HSD and BDE-100 due to activation of CYP17, a corresponding
      failure to activate CYP19 expression and inhibition of CYP19 activity was seen.
      The lack of an effect of BDE-99 on the expression and activity of all of the
      investigated enzymes indicates action on enzymes before progesterone secretion,
      i.e., STAR or 3beta-HSD activity.

PMID- 21871954
TI  - Proteasome alterations during adipose differentiation and aging: links to
      impaired adipocyte differentiation and development of oxidative stress.
AB  - Intracellular proteins are degraded by a number of proteases, including the
      ubiquitin-proteasome pathway (UPP). Impairments in the UPP occur during the aging
      of a variety of tissues, although little is known in regards to age-related
      alterations to the UPP during the aging of adipose tissue. The UPP is known to be
      involved in regulating the differentiation of a variety of cell types, although
      the potential changes in the UPP during adipose differentiation have not been
      fully elucidated. How the UPP is altered in aging adipose tissue and adipocyte
      differentiation and the effects of proteasome inhibition on adipocyte homeostasis
      and differentiation are critical issues to elucidate experimentally. Adipogenesis
      continues throughout the life of adipose tissue, with continual differentiation
      of preadipocytes essential to maintaining tissue function during aging, and UPP
      alterations in mature adipocytes are likely to directly modulate adipose function
      during aging. In this study we demonstrate that aging induces alterations in the
      activity and expression of principal components of the UPP. Additionally, we show
      that multiple changes in the UPP occur during the differentiation of 3T3-L1 cells
      into adipocytes. In vitro data link observed UPP alterations to increased levels
      of oxidative stress and altered adipose biology relevant to both aging and
      differentiation. Taken together, these data demonstrate that changes in the UPP
      occur in response to adipose aging and adipogenesis and strongly suggest that
      proteasome inhibition is sufficient to decrease adipose differentiation, as well
      as increasing oxidative stress in mature adipocytes, both of which probably
      promote deleterious effects on adipose aging.

PMID- 21871955
TI  - Possible role of serotoninergic system in the neurobehavioral impairment induced
      by acute methylmercury exposure in zebrafish (Danio rerio).
AB  - Adult zebrafish were treated acutely with methylmercury (1.0 or 5.0 MUg g(-1),
      i.p.) and, 24h after treatment, were tested in two behavioral models of anxiety,
      the novel tank and the light/dark preference tests. At the smaller dose,
      methylmercury produced a marked anxiogenic profile in both tests, while the
      greater dose produced hyperlocomotion in the novel tank test. These effects were
      accompanied by a decrease in extracellular levels of serotonin, and an increase
      in extracellular levels of tryptamine-4,5-dione, a partially oxidized metabolite
      of serotonin. A marked increase in the formation of malondialdehyde, a marker of
      oxidative stress, accompanied these parameters. It is suggested that
      methylmercury-induced oxidative stress produced mitochondrial dysfunction and
      originated tryptamine-4,5-dione, which could have further inhibited tryptophan
      hydroxylase. These results underscore the importance of assessing acute, low
      level neurobehavioral effects of methylmercury.

PMID- 21871958
TI  - Dehydration of detomidine hydrochloride monohydrate.
AB  - The thermodynamic stability of detomidine hydrochloride monohydrate has been
      evaluated on the basis of phase transition kinetics in solid state. A method free
      of empirical models was used for the treatment of kinetic data, and compared to
      several known solid state kinetic data processing methods. Phase transitions were
      monitored by powder X-ray diffraction (PXRD) and thermal analysis. Full PXRD
      profiles were used for determining the phase content instead of single reflex
      intensity measurements, in order to minimize the influence of particle texture.
      We compared the applicability of isothermal and nonisothermal methods to our
      investigation of detomidine hydrochlorine monohydrate dehydration.

PMID- 21871956
TI  - Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction
      in Alzheimer's disease: implications for early intervention and therapeutics.
AB  - Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease
      affecting thousands of people in the world and effective treatment is still not
      available. Over two decades of intense research using AD postmortem brains,
      transgenic mouse and cell models of amyloid precursor protein and tau revealed
      that amyloid beta (Abeta) and hyperphosphorylated tau are synergistically
      involved in triggering disease progression. Accumulating evidence also revealed
      that aging and amyloid beta-induced oxidative DNA damage and mitochondrial
      dysfunction initiate and contributes to the development and progression of the
      disease. The purpose of this article is to summarize the latest progress in aging
      and AD, with a special emphasis on the mitochondria, oxidative DNA damage
      including methods of its measurement. It also discusses the therapeutic
      approaches against oxidative DNA damage and treatment strategies in AD.

PMID- 21871959
TI  - A comparative study on the effectiveness of cis- and trans-form of cinnamic acid
      treatments for inhibiting invasive activity of human lung adenocarcinoma cells.
AB  - Lung cancer is the major cause of tumor-related death, and approximately 70% of
      lung cancer patients die from metastasis. Evidence that phenolic compounds may
      have a potential inhibitory effect on cancer invasion and metastasis is
      increasingly being reported in the scientific literature. Cinnamic acid is a
      member of phenolics which having several isoforms in nature. The trans-cinnamic
      acid (t-CA) has been investigated extensively for its potential pharmacological
      effects whereas the study of cis-cinnamic acid (c-CA) is limited because pure c
      CA was hard to obtain. We had developed a practicable method previously to
      transform and obtain pure c-CA, and the pure compound was used to evaluate the
      anti-invasive effect on human adenocarcinoma A549 cells. The A549 cells were
      treated with 0-200 MUM of c-CA and t-CA in the presence of 200 nM phorbol-12
      myristate-13-acetate (PMA) at 37  degrees C for 24 h, and matrix
      metalloproteinase (MMP)-2, MMP-9, adhesive, migratory, and invasive activities of
      the cells were determined. The results showed that the treatment of c-CA and t-CA
      dose-dependently reduced the PMA-induced MMP-2 and -9 activities but without
      significant effect on the adhesive activity of cells. The PMA-induced motility
      was suppressed in a dose-dependent manner by a 24-h treatment with c-CA and t-CA.
      The invasive ability was significantly (p<0.05) reduced to 68% and 65%,
      respectively, relative to PMA treatment alone after treatment of PMA-treated A549
      cells with either 50 MUM c-CA or 100 MUM t-CA for 24 h. The results suggest that
      both of the c-CA and t-CA are inhibitors for invasion of A549 cells and the
      activity of c-CA seems to be higher than t-CA.

PMID- 21871957
TI  - Diffusion tensor imaging of cerebral white matter integrity in cognitive aging.
AB  - In this article we review recent research on diffusion tensor imaging (DTI) of
      white matter (WM) integrity and the implications for age-related differences in
      cognition. Neurobiological mechanisms defined from DTI analyses suggest that a
      primary dimension of age-related decline in WM is a decline in the structural
      integrity of myelin, particularly in brain regions that myelinate later
      developmentally. Research integrating behavioral measures with DTI indicates that
      WM integrity supports the communication among cortical networks, particularly
      those involving executive function, perceptual speed, and memory (i.e., fluid
      cognition). In the absence of significant disease, age shares a substantial
      portion of the variance associated with the relation between WM integrity and
      fluid cognition. Current data are consistent with one model in which age-related
      decline in WM integrity contributes to a decreased efficiency of communication
      among networks for fluid cognitive abilities. Neurocognitive disorders for which
      older adults are at risk, such as depression, further modulate the relation
      between WM and cognition, in ways that are not as yet entirely clear.
      Developments in DTI technology are providing a new insight into both the
      neurobiological mechanisms of aging WM and the potential contribution of DTI to
      understanding functional measures of brain activity. This article is part of a
      Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

PMID- 21871961
TI  - Sample clean-up by sol-gel immunoaffinity chromatography for the determination of
      bisphenol A in food and urine.
AB  - Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is an industrial chemical
      mainly used as a monomer in the synthesis of polycarbonates and epoxy resins. BPA
      has been shown to elicit estrogenic effects via binding to the nuclear estrogen
      receptors alpha and beta. Food is considered as the major source of BPA exposure
      for the general human population. When incorporated into the body, BPA is
      metabolised in the liver, mainly to BPA glucuronide, and excreted via the urine.
      The present paper presents analytical methods for the determination of BPA
      concentrations in foodstuffs and the determination of free and total (free plus
      conjugated) BPA in urine samples. The paper provides protocols for the
      preparation and operation of sol-gel immunoaffinity columns and their application
      to remove interfering matrix compounds and to enrich BPA. In addition, the paper
      points out major sources of systematic errors in BPA analysis and describes how
      they can be avoided.

PMID- 21871960
TI  - Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of
      simvastatin.
AB  - The role of autophagy, a process in which the cell self-digests its own
      components, was investigated in glioma cell death induced by the
      hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin.
      Induction of autophagy and activation of autophagy-regulating signalling pathways
      were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used
      to assess autophagy-associated intracellular acidification and apoptotic markers
      (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell
      viability was determined by crystal violet, MTT or LDH release assay. Simvastatin
      treatment of U251 and C6 glioma cell lines caused the appearance of
      autophagolysosome-like intracytoplasmic acidic vesicles. The induction of
      autophagy in U251 cells was confirmed by the upregulation of autophagosome
      associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation
      of the selective autophagic target p62. Simvastatin induced the activation of AMP
      activated protein kinase (AMPK) and its target Raptor, while simultaneously
      downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major
      AMPK/Akt downstream target and a major negative autophagy regulator, and its
      substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the
      product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological
      inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10
      DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by
      simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and
      LC3beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly
      increased apoptotic death of simvastatin-treated U251 cells. These data suggest
      that inhibition of AMPK-dependent autophagic response might sensitize glioma
      cells to statin-induced apoptotic death.

PMID- 21871963
TI  - Recent advances in imaging embryonic myoblast fusion in Drosophila.
AB  - Myoblast fusion in the Drosophila embryos is a complex process that includes
      changes in cell movement, morphology and behavior over time. The advent of
      fluorescent proteins (FPs) has made it possible to track and image live cells, to
      capture the process of myoblast fusion, and to carry out quantitative analysis of
      myoblasts in real time. By tagging proteins with FPs, it is also possible to
      monitor the subcellular events that accompany the fusion process. Herein, we
      discuss the recent progress that has been made in imaging myoblast fusion in
      Drosophila, reagents that are now available, and microscopy conditions to
      consider. Using an Actin-FP fusion protein along with a membrane marker to
      outline the cells, we show the dynamic formation and breakdown of F-actin foci at
      sites of fusion. We also describe the methods used successfully to show that
      these foci are primarily if not wholly present in the fusion-competent myoblasts.

PMID- 21871962
TI  - Immunoaffinity purification of peptide hormones prior to liquid chromatography
      mass spectrometry in doping controls.
AB  - For most peptide hormones prohibited in elite sports the concentrations in plasma
      or urine are very low (pg/mL). Accordingly, hyphenated purification and
      enrichment steps prior to mass spectrometric detection are required to obtain
      sufficient doping control assays. Immunoaffinity purification in combination with
      nano-scale liquid chromatography coupled to high resolution/high accuracy mass
      spectrometry was found to have the potential of providing the necessary
      sensitivity and unambiguous specificity to produce reliable results. With the
      presented methodology 12 prohibited peptides (porcine insulin, Novolog, Apidra,
      Lantus DesB30-32 metabolite, Humalog and human insulin, Synacthen (synthetic ACTH
      analogue), luteinizing hormone-releasing hormone (LH-RH), growth hormone
      releasing hormone (GH-RH(1-29)) and CJC-1295 (GH-RH analogue), LongR(3)-IGF-1 and
      IFG-1) were simultaneously purified from plasma/serum or urine. With limits of
      detection for each target compound ranging in the low pg/mL level (urine), the
      method enables the determination of urinary peptides at physiologically relevant
      concentrations. For each class of peptides an appropriate antibody and a
      respective internal standard was implemented ensuring robust analysis conditions.
      Due to the fast and simple sample preparation procedure (~25 samples per day) and
      the fact that all materials are commercial available, the implementation of the
      methodology to laboratories from other analytical fields (forensics,
      pharmacokinetic sciences, etc.) is enabled.

PMID- 21871964
TI  - Rational recombinant XMRV antigen preparation and bead coupling for multiplex
      serology in a suspension array.
AB  - Diagnosis of infectious diseases often requires demonstration of antibodies to
      the microbe (serology). A large set of antigens, covering viruses, bacteria,
      fungi and parasites may be needed. Recombinant proteins have a prime role in
      serological tests. Suspension arrays offer high throughput for simultaneous
      measurement of many different antibodies. We here describe a rational process for
      preparation, purification and coupling to beads of recombinant proteins prepared
      in Escherichia coli derivate Origami B, to be used in a serological Luminex
      suspension array. All six Gag and Env proteins (p10, p12, p15, p30, gp70 and
      p15E), from the xenotropic murine leukemia virus-related virus (XMRV), were
      prepared, allowing the creation of a multiepitope XMRV antibody assay. The
      procedure is generic and allows production of protein antigens ready for
      serological testing in a few working days. Instability and aggregation problems
      were circumvented by expression of viral proteins fused to a carrier protein
      (thioredoxin A; TrxA), purification via inclusion body formation, urea
      solubilization, His tag affinity chromatography and direct covalent coupling to
      microspheres without removal of the elution buffer. The yield of one preparation
      (2-10mg fusion protein per 100ml culture) was enough for 20-100 coupling
      reactions, sufficing for tests of many tens of thousands of sera. False
      serological positivity due to antibodies binding to TrxA and to traces of E. coli
      proteins remaining in the preparation could be reduced by preabsorption of sera
      with free TrxA and E. coli extract. The recombinant antigens were evaluated using
      anti-XMRV antibodies. Although hybrid proteins expressed in E. coli in this way
      will not have the entire tertiary structure and posttranslational modifications
      of the native proteins, they contain a large subset of the epitopes associated
      with them. The described strategy is simple, quick, efficient and cheap. It
      should be applicable for suspension array serology in general.

PMID- 21871966
TI  - Selectivity in biomineralization of barium and strontium.
AB  - The desmid green alga Closterium moniliferum belongs to a small number of
      organisms that form barite (BaSO(4)) or celestite (SrSO(4)) biominerals. The
      ability to sequester Sr in the presence of an excess of Ca is of considerable
      interest for the remediation of (90)Sr from the environment and nuclear waste.
      While most cells dynamically regulate the concentration of the second messenger
      Ca(2+) in the cytosol and various organelles, transport proteins rarely
      discriminate strongly between Ca, Sr, and Ba. Herein, we investigate how these
      ions are trafficked in C. moniliferum and how precipitation of (Ba,Sr)SO(4)
      crystals occurs in the terminal vacuoles. Towards this goal, we simultaneously
      visualize intracellular dynamics of multiple elements using X-ray fluorescence
      microscopy (XFM) of cryo-fixed/freeze-dried samples. We correlate the resulting
      elemental maps with ultrastructural information gleaned from freeze-fracture cryo
      SEM of frozen-hydrated cells and use micro X-ray absorption near edge structure
      (micro-XANES) to determine sulfur speciation. We find that the kinetics of Sr
      uptake and efflux depend on external Ca concentrations, and Sr, Ba, and Ca show
      similar intracellular localization. A highly ion-selective cross-membrane
      transport step is not evident. Based on elevated levels of sulfate detected in
      the terminal vacuoles, we propose a "sulfate trap" model, where the presence of
      dissolved barium leads to preferential precipitation of (Ba,Sr)SO(4) due to its
      low solubility relative to SrSO(4) and CaSO(4). Engineering the sulfate
      concentration in the vacuole may thus be the most direct way to increase the Sr
      sequestered per cell, an important consideration in using desmids for
      phytoremediation of (90)Sr.

PMID- 21871965
TI  - An overview of enzymatic reagents for the removal of affinity tags.
AB  - Although they are often exploited to facilitate the expression and purification
      of recombinant proteins, every affinity tag, whether large or small, has the
      potential to interfere with the structure and function of its fusion partner. For
      this reason, reliable methods for removing affinity tags are needed. Only enzymes
      have the requisite specificity to be generally useful reagents for this purpose.
      In this review, the advantages and disadvantages of some commonly used endo- and
      exoproteases are discussed in light of the latest information.

PMID- 21871967
TI  - Phylogeny, biogeography, and display evolution in the tree and brush lizard genus
      Urosaurus (Squamata: Phrynosomatidae).
AB  - The brush and tree lizards (Urosaurus) are a small clade of phrynosomatid lizards
      native to western North America. Though not as well known as their diverse sister
      clade, the spiny lizards (Sceloporus), some Urosaurus have nonetheless become
      model organisms in integrative biology. In particular, dramatic phenotypic and
      behavioral differences associated with specific mating strategies have been
      exploited to address a range of ecological and evolutionary questions. However,
      only two phylogenies have been proposed for the group, one of which is pre
      cladistic and both based principally on morphological characters that might not
      provide robust support for relationships within the group. To help provide
      investigators working on Urosaurus with a robust phylogeny in which to frame
      ecological and evolutionary questions, we establish a molecular phylogeny for the
      group. We sampled three mitochondrial and three nuclear loci, and estimated
      phylogenetic relationships within Urosaurus using both maximum parsimony (MP) and
      Bayesian inference (BI), as well as a coalescent-based species tree approach.
      Finally, we used two methods of ancestral state reconstruction (ASR) to gain
      insight into the evolution of microhabitat preference and male display signals,
      traits that have been the focus of studies on Urosaurus. All reconstruction
      methods yield nearly the same ingroup topology that is concordant in most
      respects with the previous cladistic analysis of the group but with some
      significant differences; our data suggest the primary divergence in Urosaurus
      occurs between a clade endemic to the Pacific versant of Mexico and the lineages
      of Baja California and the southwestern US, rather than placing Urosaurus
      graciosus as the basal taxon and linking the Baja and Mexican endemics. We find
      support for a single transition to a saxicolous lifestyle within the group, and
      either the independent gain or loss of arboreality. The evolution of throat color
      patterns (i.e. dewlaps) appears complex, with multiple color morphs likely
      involving orange reconstructed as ancestral to the group and to most lineages,
      followed by a single transition to a fixed blue-throated morph in one clade.
      These results should provide a useful framework for additional comparative work
      with Urosaurus, and establish the phylogenetic context in which Urosaurus
      diversity arose.

PMID- 21871968
TI  - Atypical PKCzeta transduces electrophilic fatty acid signaling in pulmonary
      epithelial cells.
AB  - Nitric oxide and secondary oxides of nitrogen react with unsaturated fatty acids
      such as linoleic acid to yield oxidized and nitrated products. Fatty acid
      nitroalkene derivatives, (e.g. nitrolinoleate [LNO(2)]) are produced by oxidative
      inflammatory reactions, detected clinically, display potent electrophilic
      reactivity and induce post-translational protein modifications that mediate
      adaptive inflammatory signaling responses. LNO(2) signaling was examined in lung
      epithelial cells because the alveolar compartment is a rich site for the
      transduction of redox and inflammatory reactions. LNO(2) did not directly induce
      Ca(2+) influx in cultured lung epithelial cells, but inhibited bradykinin-induced
      Ca(2+) influx in a cGMP-independent manner. In contrast, LNO(2) activated MAP
      kinase (Erk1/2) by a mechanism independent of bradykinin. It was hypothesized
      that these unique responses were transduced by activation of different protein
      kinase C isotypes, supported by the observation that LNO(2)-mediated inhibition
      of Ca(2+) influx was blocked by the non-selective PKC inhibitors chelerythine
      chloride and calphostin C, but not by the calcium dependent "classic" PKC
      inhibitor Go6976. Western blot analysis showed that atypical PKCzeta was
      activated by LNO(2) stimulation, with PKCzeta and Erk activation also
      demonstrated in primary culture of human lung type II cells. Addition of
      pseudotypical PKCzeta substrate peptide reversed LNO(2)-mediated induction of
      Ca(2+) influx and MAP kinase activation. Finally, the electrophilic nature of
      LNO(2) resulted in a novel mode of PKCzeta activation, covalent adduction of the
      enzyme. In summary, LNO(2) mediated signaling in lung type II epithelial cells
      occurs via a unique pathway involving PKCzeta.

PMID- 21871969
TI  - Glucosensing and glucose homeostasis: from fish to mammals.
AB  - This review is focused on two topics related to glucose in vertebrates. In a
      first section devoted to glucose homeostasis we describe how glucose levels
      fluctuate and are regulated in different classes of vertebrates. The detection of
      these fluctuations is essential for homeostasis and for other physiological
      processes such as regulation of food intake. The capacity of that detection is
      known as glucosensing, and the different mechanisms through which it occurs are
      known as glucosensors. Different glucosensor mechanisms have been demonstrated in
      different tissues and organs of rodents and humans whereas the information
      obtained for other vertebrates is scarce. In the second section of the review we
      describe the present knowledge regarding glucosensor mechanisms in different
      groups of vertebrates, with special emphasis in fish.

PMID- 21871970
TI  - A quality alert and call for improved curation of public chemistry databases.
AB  - In the last ten years, public online databases have rapidly become trusted
      valuable resources upon which researchers rely for their chemical structures and
      data for use in cheminformatics, bioinformatics, systems biology, translational
      medicine and now drug repositioning or repurposing efforts. Their utility depends
      on the quality of the underlying molecular structures used. Unfortunately, the
      quality of much of the chemical structure-based data introduced to the public
      domain is poor. As an example we describe some of the errors found in the
      recently released NIH Chemical Genomics Center 'NPC browser' database as an
      example. There is an urgent need for government funded data curation to improve
      the quality of internet chemistry and to limit the proliferation of errors and
      wasted efforts.

PMID- 21871971
TI  - Fecal bacterial contamination in natural water reservoirs as an indicator of
      seasonal infection by Opisthorchis viverrini in snail intermediate hosts.
AB  - Opisthorchis viverrini, a carcinogenic liver fluke, requires Bithynia snails as
      the first intermediate host, which release cercariae after ingesting fluke eggs
      from contaminated water. Fecal bacterial contamination and O. viverrini-infected
      Bithynia snails were investigated in samples collected from natural water
      reservoirs in Ban Phai, Chonnabot and Muang Districts (Ban Lerngpeuy) in Khon
      Kaen Province, northeast Thailand, where there is a high incidence of
      cholangiocarcinoma. Water was sampled and examined six times (February, April,
      June, August, October and December 2006). The most probable number (MPN) index
      and coliform counts were utilized to evaluate fecal contamination; the cercarial
      shedding method was conducted for detecting infected snails. The data revealed
      that all water samples had a high MPN index number, and fecal coliform levels
      above the WHO standard. This indicated that water in these reservoirs was
      contaminated with feces or manure constituents. Water sampling from Ban Lerngpeuy
      showed full-scale bacterial contamination (>1609 MPN index) throughout the year.
      This finding was correlated with the highest prevalence of O. viverrini-infected
      snails, which were found nearly all year round in this area. Slightly lower fecal
      contamination levels were detected in water samples from Chonnabot and Ban Phai,
      with high MPN index numbers and coliform counts from April to October. This
      corresponded with the higher recovery of infected snails in June and August, but
      with relatively lower prevalence than those found in Ban Lerngpeuy. Among the
      sampling sites, the people in Ban Lerngpeuy live nearer to the reservoir than do
      those in Ban Phai and Chonnabot. These results indicate that fecal bacterial
      contamination in natural water reservoirs is an important indicator of seasonal
      transmission of O. viverrini eggs to snail intermediate hosts. Sanitation
      improvement is essential and future investigations on the sources of
      contamination are needed.

PMID- 21871972
TI  - Molecular characterization of Theileria orientalis causing fatal infection in
      crossbred adult bovines of South India.
AB  - The disease condition attributed to have been caused by Theileria orientalis is
      generally benign. However, it is also thought that the parasite, at least some
      strains of it, can cause fatal disease. The present communication deals with the
      clinical signs, postmortem lesions and diagnosis of a fatal disease due to T.
      orientalis which caused mortality in crossbred adult bovines of South India. High
      body temperature, lacrimation, nasal discharge, swollen lymph nodes and
      haemoglobinuria were the symptoms observed. The postmortem lesions observed were
      punched out ulcers in abomasum, enlargement of spleen, massive pulmonary oedema,
      frothy exudates in trachea, epicardial and endocardial haemorrhage and
      haemorrhagic duodenitis. Peripheral blood smear examination revealed rod shaped
      Theileria sp. organisms. Polymerase chain reaction that amplify the T. orientalis
      specific P(32/33) gene, followed by cloning and sequencing, revealed maximum
      homology with Narathiwat (Thailand) and Jingole -1 (Indonesia) isolates which
      were positioned as isolate type 7 of T. orientalis.

PMID- 21871973
TI  - Molecular methods and platforms for infectious diseases testing a review of FDA
      approved and cleared assays.
AB  - The superior sensitivity and specificity associated with the use of molecular
      assays has greatly improved the field of infectious disease diagnostics by
      providing clinicians with results that are both accurate and rapidly obtained.
      Herein, we review molecularly based infectious disease diagnostic tests that are
      Food and Drug Administration approved or cleared and commercially available in
      the United States as of December 31, 2010. We describe specific assays and their
      performance, as stated in the Food and Drug Administration's Summary of Safety
      and Effectiveness Data or the Office of In Vitro Diagnostic Device Evaluation and
      Safety's decision summaries, product inserts, or peer-reviewed literature. We
      summarize indications for testing, limitations, and challenges related to
      implementation in a clinical laboratory setting for a wide variety of common
      pathogens. The information presented in this review will be particularly useful
      for laboratories that plan to implement or expand their molecular offerings in
      the near term.

PMID- 21871974
TI  - Autoimmune disease: A role for new anti-viral therapies?
AB  - Many chronic human diseases may have an underlying autoimmune mechanism. In this
      review, the author presents a case of autoimmune CIU (chronic idiopathic
      urticaria) in stable remission after therapy with a retroviral integrase
      inhibitor, raltegravir (Isentress). Previous reports located using the search
      terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base
      are reviewed suggesting that novel anti-viral agents such as retroviral integrase
      inhibitors, gene silencing therapies and eventually vaccines may provide new
      options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and
      experimental evidence suggests that increased replication of epigenomic viral
      pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases
      such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and
      multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a
      pathologic mechanism. Memory B cells are the reservoir of infection of EBV and
      also express endogenous retroviruses, thus depletion of memory b-lymphocytes by
      monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in
      addition to effects on B-lymphocyte presentation of both EBV and HERV
      superantigens. Other novel anti-viral therapies of chronic autoimmune diseases,
      such as retroviral integrase inhibitors, could be effective, although not without
      risk.

PMID- 21871975
TI  - On the crucial ventilatory setting adjustment from two- to one-lung ventilation.
AB  - Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were
      studied aiming to evaluate the need to readjust ventilatory pattern when going
      from two- to one-lung ventilation (OLV). Wistar rats were assigned to three
      groups: the left lung was not ventilated while the right lung received: (1) tidal
      volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O
      (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and
      PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar
      collapse and impaired lung function. Higher PEEP minimized these changes and
      prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a
      higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma
      and higher PCIII expression resulted. In conclusion, the association of low V(T)
      and an adequate PEEP level could be useful to maintain arterial oxygenation
      without inducing a possible inflammatory/remodeling response.

PMID- 21871976
TI  - Refractory calciphylaxis.

PMID- 21871977
TI  - A simplified incision of the external oblique aponeurosis during the components
      separation technique for the repair of large incisional hernias.
AB  - Incising the external oblique muscle aponeurosis is an important part of the
      components separation technique for the repair of large incisional hernias.
      Endoscopically assisted section has been suggested to prevent complications of
      extensive skin flap formation. We used a simplified method for incising the
      external oblique aponeurosis, using a modified Collin Hartmann retractor, in 14
      patients for the repair of large incisional hernias. Eight women and 6 men, with
      a mean (+/- standard deviation) age of 61.9 +/- 14.9 years, underwent surgery.
      The median transverse diameter of the defect was 8.6 +/- 3.0 cm. No postoperative
      morbidity occurred except 1 case of skin necrosis. One patient had a recurrence.
      Sectioning the external oblique aponeurosis during the components separation
      method using the technique described is a simple, safe, and economic approach
      that can prevent the complications described after the original techniques.

PMID- 21871978
TI  - Postoperative long-term evaluation of interposition reconstruction compared with
      Roux-en-Y after total gastrectomy in gastric cancer: prospective randomized
      controlled trial.
AB  - BACKGROUND: The postoperative clinical superiority of the interposition of
      jejunum reconstruction (INT) to Roux-en-Y reconstruction (RY) after total
      gastrectomy has not been clarified. Postoperative quality of life (QOL) was
      evaluated between the 2 methods by a multi-institutional prospective randomized
      trial. METHODS: A total of 103 patients with gastric cancer were prospectively
      randomly divided into groups for RY (n = 51) or INT reconstruction (n = 52) after
      total gastrectomy. They were stratified by sex, age, institute, histology, and
      degree of lymph node dissection. Postoperatively, body mass index (BMI) and
      nutritional conditions were measured serially, and QOL and postoperative squalor
      scores were evaluated at 3, 12, and 60 months and compared between the 2 groups.
      RESULTS: After removing patients who did not complete the follow-up survey or
      censured cases, 24 patients in the RY group and 18 patients in the INT group were
      clinically available and their postoperative status was assessed. QOL scores were
      increased and complication scores were improved in the postoperative periods (P <
      .01). Postoperative BMI significantly deteriorated compared with preoperative BMI
      in each group. The postoperative QOL and complication scores at 60 months after
      surgery were significantly better than those at 3 months after surgery in each
      group (P < .01). However, there was no significant difference of QOL scores and
      postoperative complication scores between the 2 reconstruction groups. The
      nutritional condition in the INT group was nearly the same as that in the RY
      group. CONCLUSIONS: Although our patient sample was small and patients who did
      not complete the follow-up survey were present, we could not identify any
      clinical difference between INT and RY after total gastrectomy 60 months after
      surgery. The safer and simpler RY method may be a more suitable reconstruction
      method than INT after total gastrectomy.

PMID- 21871979
TI  - Prospective randomized comparative study of single incision laparoscopic
      cholecystectomy versus conventional four-port laparoscopic cholecystectomy.
AB  - BACKGROUND: This study aimed to compare the outcomes of single-incision
      laparoscopic cholecystectomy (SILC) versus conventional 4-port laparoscopic
      cholecystectomy (LC). METHODS: From November 2009 to August 2010, 51 patients
      with symptomatic gallstone or gallbladder polyps were randomized to SILC (n = 24)
      or 4-port LC (n = 27). RESULTS: Mean surgical time (43.5 vs 46.5 min), median
      blood loss (1 vs 1 mL) and mean hospital stay (1.5 vs 1.8 d) were similar for
      both the SILC and 4-port LC group. There were no open conversions and no major
      complications. The mean total wound length of the SILC group was significantly
      shorter (1.76 vs 2.25 cm). The median visual analogue pain score at 6 hours after
      surgery was similar (4.5 vs 4.0) but the SILC group had a significantly worse
      pain score on day 7 (1 vs 0). There was no difference in time to resume usual
      activity (mean, 5.6 vs 5.0 d). The median cosmetic score of SILC was
      significantly higher than at 3 months after surgery (7 vs 6). CONCLUSIONS: SILC
      was feasible and safe for properly selected patients in experienced hands.

PMID- 21871980
TI  - Incidence of and risk factors for anastomotic leakage after laparoscopic anterior
      resection with intracorporeal rectal transection and double-stapling technique
      anastomosis for rectal cancer.
AB  - BACKGROUND: Laparoscopic rectal cancer surgery involving rectal division with
      intracorporeal stapling devices is technically difficult. This study aimed to
      identify risk factors for anastomotic leakage associated with laparoscopic
      anterior resection for rectal cancer. METHODS: We studied 363 patients who
      underwent laparoscopic anterior resection with intracorporeal rectal transection
      and double-stapling technique (DST) anastomosis for rectal cancer between July
      2005 and February 2010. Twenty-two independent clinical variables were examined
      by univariate and multivariate analyses. The outcome of interest was clinical
      anastomotic leakage. RESULTS: Anastomotic leakage was identified in 13 (3.6%)
      patients. Multivariate analysis identified middle/lower rectal cancer (odds
      ratio, 9.446) and lack of pelvic drain (odds ratio, 3.814) as independent
      predictive factors for anastomotic leakage. The number of cartridges used for
      rectal division had no significant impact on anastomotic leakage. CONCLUSIONS:
      Laparoscopic anterior resection involving intracorporeal rectal transection and
      DST anastomosis is safe if performed using an appropriate technique.

PMID- 21871981
TI  - Complex hepatobiliary surgery in the community setting: is it safe and feasible?
AB  - BACKGROUND: Complex hepatobiliary surgical procedures for benign and malignant
      conditions are regularly performed at tertiary academic referral centers with
      excellent outcomes, but whether similar surgical outcomes are achievable in
      community hospitals is not well documented. METHODS: Eighty-four patients
      underwent complex hepatobiliary surgery between December 2004 and December 2008.
      Data were prospectively analyzed, including patient demographics, operative
      procedures, perioperative parameters, pathology, complications up to 30 days
      postoperatively, and long-term outcomes. RESULTS: The most frequent procedures
      performed were isolated segmentectomy or segmentectomies (n = 41 [49%]). Major
      hepatic resections (n = 32 [38%]) included 25 lobectomies (30%) and 7
      trisegmentectomies (8%). Nine patients (11%) had surgical complications, and the
      most common indications for surgery was metastatic carcinoma (n = 42 [50%]).
      CONCLUSIONS: Complex hepatobiliary surgery can be performed safely at a community
      based teaching hospital with excellent outcomes. In the ongoing debate centering
      on mandatory referral and centralization of complex surgical procedures, tertiary
      community hospitals with well-determined outcomes should be included.

PMID- 21871982
TI  - Acute appendicitis--not just for the young.
AB  - BACKGROUND: The incidence of appendicitis is highest in young patients, but the
      number of elderly patients with appendicitis appears to be increasing. The
      authors evaluated a statewide experience to assess the effect of age on resource
      utilization and outcomes for this common disease. METHODS: All discharges from
      Kentucky hospitals for appendicitis were identified. Patients from rehabilitation
      hospitals, those with inflammatory bowel disease, and those undergoing incidental
      appendectomy were excluded. RESULTS: Young (aged <= 29 years) and middle-aged
      (aged 30-64 years) patients each constituted 45% of all patients with
      appendicitis. Length of stay, hospital charges, and frequency of complicated
      appendicitis all increased with age. Although elderly patients (aged >= 80 years)
      underwent laparoscopic appendectomy as frequently (60%) as younger patients, they
      were more likely to undergo complicated open procedures. CONCLUSIONS: Older
      patients represent a substantial population of patients with appendicitis, with
      more complicated operative procedures, increased lengths of stay, and increased
      resource utilization.

PMID- 21871984
TI  - Contralateral prophylactic mastectomy in breast cancer patients who test negative
      for BRCA mutations.
AB  - BACKGROUND: Determination of BRCA1 and 2 mutation carrier status is important.
      Although BRCA carriers are offered bilateral mastectomy and oophorectomy, most
      who test negative decline. Some women choose contralateral prophylactic
      mastectomy (CPM) at the time of their breast cancer diagnosis despite testing
      negative. METHODS: A total of 110 women with breast cancer received genetic
      testing before surgical treatment. Patient demographics, tumor characteristics,
      surgical treatment, and magnetic resonance imaging use were recorded. RESULTS:
      Results revealed BRCA1/2 mutation in 33%, variant of unknown significance in 6%,
      and no mutation in 61% of women. In BRCA-negative women, 37% chose CPM. Marital
      status was significant for CPM (P = .03). Race, age, stage of presentation, and
      biomarker status were not associated with choice of CPM. Ninety-six percent of
      CPM recipients underwent breast reconstruction. Magnetic resonance imaging use
      did not affect CPM rates (P = .99). CONCLUSIONS: Increased rates of CPM have been
      observed. In our study married women were more likely to choose CPM. We recommend
      genetic genotyping before surgery. These findings warrant further investigation.

PMID- 21871983
TI  - Laparoscopic ultralow anterior resection versus laparoscopic pull-through with
      coloanal anastomosis for rectal cancers: a comparative study.
AB  - BACKGROUND: Ultralow anterior resection for mid and distal rectal cancers has
      been reported routinely performed using either a laparoscopic ultralow anterior
      resection (LAR) or laparoscopic pull-through with coloanal anastomosis (LPT).
      This study evaluated the postoperative and functional outcomes. METHODS: Between
      January 2007 and December 2008, 40 consecutive patients had laparoscopic surgery
      for rectal cancers. The data were prospectively collected. RESULTS: There were 21
      patients (21 men; mean age 61.2 +/- 3.2 years standard error of the mean [SEM])
      in the LAR group and 19 (16 men; mean age 61.4 +/- 2.4 years SEM) in the LPT
      group. Tumor characteristics, adjuvant therapy given, mean follow-up (overall
      33.5 +/- 1.4 months SEM), intraoperative time, blood loss, mesorectum quality,
      conversion rate (LAR n = 2, LPT n = 1), pain score, time for ileostomy to
      function, subsequent incontinence scores, and complication rates (LAR n = 7, LPT
      n = 9) were not different between groups, but benign anastomotic strictures were
      higher after LPT (n = 4, LAR n = 0, P = .042). The latter was associated with
      chemoradiotherapy (P = .015). There were 2 systemic cancer recurrences both in
      the LPT group but no local recurrences to date. CONCLUSIONS: The LAR technique
      may have less risk of anastomotic strictures, particularly with adjuvant therapy.
      LPT may be considered selectively for a bulky distal rectal tumor in a small
      pelvis with comparable functional results.

PMID- 21871985
TI  - Comparison of different risk-adjustment models in assessing short-term surgical
      outcome after transthoracic esophagectomy in patients with esophageal cancer.
AB  - BACKGROUND: Different risk-prediction models have been developed, but none is
      generally accepted in selecting patients for esophagectomy. This study evaluated
      5 most frequently used risk-prediction models, including the American Society of
      Anesthesiologists, Portsmouth-modified Physiological and Operative Severity Score
      for the enUmeration of Mortality and morbidity (P-POSSUM), and the adjusted
      version for Oesophagogastric surgery (O-POSSUM), Charlson and the Age adjusted
      Charlson score to assess postoperative mortality after transthoracic
      esophagectomy. METHODS: Data were obtained from 278 consecutive esophageal cancer
      patients between 1991 and 2007. Performance in predicting postoperative mortality
      (in-hospital and 90-day mortality) were analyzed regarding calibration (Hosmer
      and Lemeshow goodness-of-fit test) and discrimination (area under the receiver
      operator curve). RESULTS: The Hosmer and Lemeshow goodness-of-fit test was
      applied to each model and showed a significant outcome for only the P-POSSUM
      score (P = .035). The receiver operator curve indicated discriminatory power for
      P-POSSUM (.766) and for O-POSSUM (.756), other models did not exceed the minimal
      surface of .7. CONCLUSIONS: Postoperative mortality after esophagectomy was best
      predicted by O-POSSUM. However, it still overpredicted postoperative mortality.

PMID- 21871986
TI  - Improved outcomes after aggressive surgical resection of hilar
      cholangiocarcinoma: a critical analysis of recurrence and survival.
AB  - BACKGROUND: Hilar cholangiocarcinoma (HC) is invariably fatal without surgical
      intervention. The primary aim of the current study was to report overall survival
      and recurrence-free survival outcomes after surgical resection of HC. METHODS:
      Between December 1992 and December 2009, 85 patients were evaluated; of these, 42
      patients underwent potentially curative surgery. These patients are the principal
      subjects of this study. Patients were assessed monthly for the first 3 months and
      then at 6-month intervals after treatment. Recurrence-free survival and overall
      survival were determined; 18 clinicopathologic and treatment-related factors
      associated with recurrence-free survival and overall survival were evaluated
      through univariate and multivariate analyses. RESULTS: No patient was lost to
      follow-up evaluation. The median follow-up period was 20 months (range, 0-106
      mo). The median recurrence-free survival and overall survival after resection was
      15 and 28 months, respectively. The 5-year survival rate was 24%. Two factors
      were associated with overall survival: histologic grade (P = .002) and margin
      status (P = .033). Only histologic grade (P = .029) was associated with
      recurrence-free survival. CONCLUSIONS: Surgical resection is an efficacious
      treatment for HC. Patient selection based on identified prognostic factors can
      improve treatment outcomes.

PMID- 21871988
TI  - A framework-based approach to designing simulation-augmented surgical education
      and training programs.
AB  - The goal of simulation-based medical education and training is to help trainees
      acquire and refine the technical and cognitive skills necessary to perform
      clinical procedures. When designers incorporate simulation into programs, their
      efforts should be in line with training needs, rather than technology. Designers
      of simulation-augmented surgical training programs, however, face particular
      problems related to identifying a framework that guides the curricular design
      activity to fulfill the particular requirements of such training programs. These
      problems include the lack of (1) an objective identification of training needs,
      (2) a systematic design methodology to match training objectives with simulation
      resources, (3) structured assessments of performance, and (4) a research-centered
      view to evaluate and validate systematically the educational effectiveness of the
      program. In this report, we present a process called "Aim - FineTune -
      FollowThrough" to enable the connection of the identified problems to solutions,
      using frameworks from psychology, motor learning, education and experimental
      design.

PMID- 21871987
TI  - Evaluation of morbidity and mortality after anastomotic leakage following
      elective colorectal surgery in patients treated with or without mechanical bowel
      preparation.
AB  - BACKGROUND: A previous multicenter randomized trial demonstrated that mechanical
      bowel preparation (MBP) does not guard against anastomotic leakage in elective
      colorectal surgery. The aim of this complementary study was to evaluate the
      effects of MBP on morbidity and mortality after anastomotic leakage in elective
      colorectal surgery. METHODS: A subgroup analysis was performed of a randomized
      trial comparing the incidence of anastomotic leakage and septic complications
      with and without MBP in patients undergoing elective colorectal surgery. RESULTS:
      Elective colorectal surgery was performed in 1,433 patients with primary
      anastomoses, of whom 63 patients developed anastomotic leakage. Twenty-eight
      patients (44%) received MBP and 35 patients (56%) did not. Mortality rate,
      initial need for surgical reintervention, and extent of bowel contamination did
      not differ between groups (29% vs 40%; P = .497, P = .667, and P = .998,
      respectively). CONCLUSIONS: No benefit of MBP was found regarding morbidity and
      mortality after anastomotic leakage in elective colorectal surgery.

PMID- 21871989
TI  - Cardiothoracic surgery.
AB  - Cardiothoracic surgeons provide care to neonates, children, adults, and the
      elderly with a range of disorders of the heart, lungs, esophagus, and major blood
      vessels of the chest. The field of cardiothoracic surgery continues to thrive
      among the transformations in thoracic and cardiovascular medicine. This article
      is intended to provide a guide to medical students and physicians on the
      training, certification, research, and funding opportunities as well as societies
      and journals specific to cardiothoracic surgery.

PMID- 21871990
TI  - Orthopedic surgery.
AB  - Orthopedic surgery is a specialty of surgery dedicated to the prevention,
      diagnosis, and treatment of diseases and injuries of the musculoskeletal system
      in all age groups. Careers in orthopedic surgery span the spectrum from general
      orthopedics to those of subspecialty expertise in orthopedic trauma, hand,
      pediatrics, total joint, foot and ankle, sports medicine, and oncology to name a
      few.

PMID- 21871991
TI  - Endocrine surgery.
AB  - The increasing complexity in the management of surgical disorders of the thyroid,
      parathyroid, adrenal glands, and neuroendocrine pancreas tumors have led to the
      emergence of endocrine surgery as a surgical subspecialty. Studies showing the
      relationship between hospital/surgeon volume and patient outcomes highlight the
      importance of advanced postgraduate training in this field.

PMID- 21871992
TI  - Invited comment on: The surgical residency and ACGME reform: steep learning or
      sleep learning?

PMID- 21871994
TI  - MALT symposium.

PMID- 21871995
TI  - ST elevation: differentiation between ST elevation myocardial infarction and
      nonischemic ST elevation.
AB  - It is well accepted that early reperfusion is beneficial in patients with acute
      myocardial infarction presenting with ST elevation (STE). Earlier studies
      suggested lack of beneficial effects in patients presenting without STE and even
      with ST depression. Currently, time to reperfusion is considered to be a quality
      of care measure, and the latest American College of Cardiology/American Heart
      Association guidelines for the treatment of STE acute myocardial infarction
      (STEMI) emphasize that the physician at the emergency department should make
      reperfusion decisions within 10 minutes of performing the initial
      electrocardiogram (ECG). However, not all ECGs with STE necessarily reflect
      transmural infarction from acute thrombotic occlusion of an epicardial coronary
      artery, as a large number of patients presenting with compatible symptoms have
      baseline STE. In some cases a pattern of benign nonischemic STE (NISTE) can be
      recognized fairly easily. Other times, differentiating between true STEMI and
      NISTE may be difficult. It should be remembered that patients presenting with
      chest pain and showing benign pattern of NISTE (eg, "early repolarization" or STE
      secondary to left ventricular hypertrophy) may have true ischemic pain and non
      STE myocardial infarction or even STEMI on top of the baseline benign pattern. It
      seems that, in the "real world," the ability of physicians to differentiate NISTE
      from STEMI based on the presenting ECG pattern widely varies and depends on the
      prevalence of baseline NISTE in the patient population. Further studies are
      needed to assess the ability of various ECG criteria to accurately differentiate
      between STEMI and NISTE.

PMID- 21871996
TI  - The impact of numeric and graphic displays of ST-segment deviation levels on
      cardiologists' decisions of reperfusion therapy for patients with acute coronary
      occlusion.
AB  - The study purpose is to determine whether numeric and/or graphic ST measurements
      added to the display of the 12-lead electrocardiogram (ECG) would influence
      cardiologists' decision to provide myocardial reperfusion therapy. Twenty ECGs
      with borderline ST-segment deviation during elective percutaneous coronary
      intervention and 10 controls before balloon inflation were included. Only 5 of
      the 20 ECGs during coronary balloon occlusion met the 2007 American Heart
      Association guidelines for ST-elevation myocardial infarction (STEMI). Fifteen
      cardiologists read 4 sets of these ECGs as the basis for a "yes/no" reperfusion
      therapy decision. Sets 1 and 4 were the same 12-lead ECGs alone. Set 2 also
      included numeric ST-segment measurements, and set 3 included both numeric and
      graphically displayed ST measurements ("ST Maps"). The mean (range) positive
      reperfusion decisions were 10.6 (2-15), 11.4 (1-19), 9.7 (2-14), and 10.7 (1-15)
      for sets 1 to 4, respectively. The accuracies of the observers for the 5 STEMI
      ECGs were 67%, 69%, and 77% for the standard format, the ST numeric format, and
      the ST graphic format, respectively. The improved detection rate (77% vs 67%)
      with addition of both numeric and graphic displays did achieve statistical
      significance (P < .025). The corresponding specificities for the 10 control ECGs
      were 85%, 79%, and 89%, respectively. In conclusion, a wide variation of
      reperfusion decisions was observed among clinical cardiologists, and their
      decisions were not altered by adding ST deviation measurements in numeric and/or
      graphic displays. Acute coronary occlusion detection rate was low for ECGs
      meeting STEMI criteria, and this was improved by adding ST-segment measurements
      in numeric and graphic forms. These results merit further study of the clinical
      value of this technique for improved acute coronary occlusion treatment decision
      support.

PMID- 21871997
TI  - The relationship between initial ST-segment deviation and final QRS complex
      changes related to the posterolateral wall in acute inferior myocardial
      infarction.
AB  - OBJECTIVES: The aim of this study was to assess the relationship between initial
      ST-segment deviation and final QRS complex changes related to the posterolateral
      left ventricular wall in patients with acute inferior myocardial infarction
      receiving reperfusion therapy. The secondary aim was to determine if this
      relationship is stronger for patients who present early in the
      ischemia/infarction process in comparison with patients who present late.
      METHODS: The ST-segment depression in the leads V(1), V2, and -V6 were measured
      in the electrocardiograph (ECG) just before initiation of myocardial reperfusion.
      These leads were chosen because they represent the posterolateral wall in the
      Selvester score. In addition, the Anderson-Wilkins acuteness score was calculated
      in the admission ECG. Selvester criteria related to the posterolateral wall were
      identified in the ECG performed before hospital discharge to assess final infarct
      size. RESULTS: Fifty-six patients were included in this study. No significant
      relationship was found between the sum of initial ST-segment depression in the
      leads V(1), V(2), and -V(6), and final infarct size in the posterolateral left
      ventricular wall for the total study population (r = 0.19, P = .16). Patients
      were subgrouped by Anderson-Wilkins acuteness score of less than 3 vs 3 or more.
      In those with a low acuteness score, the amount of ST-segment depression had no
      relationship with final infarct size (r = -0.16, P = .41). However, the
      correlation was statistically significant for those with a high acuteness score
      (r = 0.42, P = .04). CONCLUSION: The initial ST-segment depression in leads V(1),
      V(2), and -V(6) can predict ECG-estimated amount of infarction in the
      posterolateral left ventricular wall in patients with acute inferior myocardial
      infarction receiving reperfusion therapy, but only in those who present early in
      the ischemia/infarction process.

PMID- 21871998
TI  - Predictors and outcome of grade 3 ischemia in patients with ST-segment elevation
      myocardial infarction undergoing primary percutaneous coronary intervention.
AB  - PURPOSE: Grade 3 ischemia (G3I: distortion of the terminal portion of the QRS
      complex) is a predictor of serious complications after acute myocardial
      infarction. However, less is known about which patients are more prone to present
      with G3I. METHODS: Patients who were enrolled in the Ongoing Tirofiban In
      Myocardial infarction Evaluation trial 2 were included. These patients were
      divided in 2 groups based on the enrolment electrocardiogram: grade 2 ischemia
      (G2I) or G3I. RESULTS: Between June 2004 and November 2007, 1308 patients with
      interpretable electrocardiograms were enrolled. Grade 3 ischemia was found in 426
      (32.6%) patients. Patients with G3I were older, more often male, more often had
      diabetes, had a Thrombolysis In Myocardial Infarction (TIMI) risk score of
      greater than 3, had 3 vessel disease, had an anterior infarction, more often
      presented in Killip class greater than 1, less often had a preprocedural TIMI 3
      flow, and less often had a myocardial blush grade 3 post-PCI. One hour post-PCI,
      residual ST deviation was higher in patients with G3I compared with patients with
      G2I. Furthermore, G3I was associated with more major cardiac events (including
      death, myocardial infarction, urgent target vessel revascularization). After
      multivariate adjustment, G3I was an independent predictor of failure of ST
      segment resolution 1 hour post-PCI (odds ratio, 1.4; 95% confidence interval, 1.1
      1.9) and 30-day mortality (odds ratio, 3.2; 95% confidence interval, 1.2-8.7).
      CONCLUSION: Grade 3 ischemia was associated with high-risk patient criteria
      (older age, diabetes, TIMI risk score >3, Killip class >1, and anterior
      myocardial infarction) and represents a subgroup of high-risk patients who seems
      to be associated with poor myocardial reperfusion and worse outcome.

PMID- 21871999
TI  - Distortion of the terminal QRS complex in patients with ST-elevation myocardial
      infarction.

PMID- 21872000
TI  - Importance of standardized assessment of late gadolinium enhancement for
      quantification of infarct size by cardiac magnetic resonance: implications for
      comparison with electrocardiogram.
AB  - BACKGROUND: Cardiac magnetic resonance (CMR) is currently considered the
      reference standard for in vivo assessment of myocardial infarction (MI). There
      is, however, no international consensus on how MI quantification from CMR should
      be performed. The aim of this study was to test how previously published manual
      quantification of MI using CMR images compares with MI quantification using a
      semiautomated, validated method and how this impacts the relationship with MI
      size estimated by 12-lead electrocardiogram (ECG). METHODS: Twenty-five patients,
      from a previously published cohort, were included in the study. All patients had
      presented with clinical signs of acute coronary syndrome 6 to 12 months before
      undergoing a CMR examination. The patients had a standard 12-lead ECG recorded at
      the time of the CMR examination. The previously reported manually quantified MI
      size was compared with MI size determined using a semiautomated method validated
      by computer phantom data, experimental in vivo and ex vivo data, and patient
      data. The MI sizes from the 2 CMR approaches were then compared with the ECG
      estimated MI size. RESULTS: There was a strong correlation between MI size
      determined with the 2 CMR methods (r(2) = 0.94, P < .001). There was, however, a
      systematic overestimation of MI size of approximately 50% by the previously
      published manually quantified MI size compared with the semiautomated method.
      This affected the comparison with estimated MI size by ECG, which showed a
      significant underestimation of MI size compared with manual CMR measurements, but
      no bias compared with the semiautomated CMR method. CONCLUSIONS: Manual
      quantification of MI size by CMR can differ significantly from semiautomated,
      validated methods taking partial volume effects into account and can lead to
      erroneous conclusions when compared with ECG.

PMID- 21872002
TI  - The relationship between serial postinfarction T wave changes and infarct size
      and ventricular function as determined by cardiac magnetic resonance imaging.
AB  - BACKGROUND: The value of sequential T wave changes on the electrocardiogram (ECG)
      has less well been described than ST-segment changes in the follow-up of patients
      with myocardial infarction (MI). We investigated whether the amplitude of T wave
      positivity correlates with infarct size (IS) and left ventricular ejection
      fraction (LVEF) measured using cardiac magnetic resonance imaging 3 months after
      reperfusion therapy. MATERIALS AND METHODS: Fifty-five patients with a first
      acute MI referred for primary percutaneous coronary intervention were included.
      Electrocardiograms were analyzed within 4 hours after reperfusion and at 3
      months, measuring T wave ampitudes in 2 contiguous infarct-related leads, summed
      up as one value called T wave amplitude. Cardiac magnetic resonance imaging was
      performed at 3 months of follow-up. Correlations between T wave amplitude, IS,
      and LVEF were tested with Pearson r correlation coefficient test. Subanalyses
      were performed using a 2-sample t test. RESULTS: A good correlation was found
      between LVEF and IS (r = -0.7, P < .0001). Most of the patients had inferior MI
      location (69%). In this group, there were significant positive correlations
      between the amount of T wave positivity and both IS (r = -0.40, P = .012) and
      LVEF (r = 0.33, P = .043). Results were similar in patients with and without an
      increase in T wave amplitude during follow-up. CONCLUSIONS: In this study of
      patients with reperfused MI, patients with inferior locations demonstrated a
      statistically significant relationship between the amount of positivity of T wave
      amplitude and both IS and LVEF measured at 3 months. Furthermore, these results
      were independent of whether the T wave positivity was persistent or evolutionary
      between the immediate postreperfusion and 3-month ECG recordings.

PMID- 21872001
TI  - A detailed guide for quantification of myocardial scar with the Selvester QRS
      score in the presence of electrocardiogram confounders.
AB  - The Selvester QRS score translates subtle changes in ventricular depolarization
      measured by the electrocardiogram into information about myocardial scar location
      and size. This estimated scar has been shown to have a high degree of correlation
      with autopsy-measured myocardial infarct size. In addition, multiple studies have
      demonstrated the value of the QRS score in post-myocardial infarct patients to
      provide prognostic information. Recent studies have demonstrated that increasing
      QRS score is predictive of increased implantable defibrillator shocks for
      ventricular tachycardia and fibrillation as well as decreased response to cardiac
      resynchronization therapy. Although QRS scoring has never achieved widespread
      clinical use, increased interest in patient selection and risk-stratification
      techniques for implantable defibrillators and cardiac resynchronization therapy
      has led to renewed interest in QRS scoring and its potential to identify which
      patients will benefit from device therapy. The QRS score criteria were updated in
      2009 to expand their use to a broader population by accounting for the different
      ventricular depolarization sequences in patients with bundle-branch/fascicular
      blocks or ventricular hypertrophy. However, these changes also introduced
      additional complexity and nuance to the scoring procedure. This article provides
      detailed instructions and examples on how to apply the QRS score criteria in the
      presence of confounding conduction types to facilitate understanding and enable
      development and application of automated QRS scoring.

PMID- 21872003
TI  - The relationships between cardiovascular magnetic resonance imaging variables of
      acute myocardial infarction and both left ventricular dysfunction and immediate
      postreperfusion ST segment recovery.
AB  - OBJECTIVE: The aim of this study is to explore the relationships between
      cardiovascular magnetic resonance imaging (CMR)-determined variables of acute
      myocardial infarction and both left ventricular (LV) dysfunction and immediate
      postreperfusion ST segment recovery. METHODS: In 79 patients with first acute
      myocardial infarction, 8 different ST segment recovery (STR) variables were
      measured 30 and 60 minutes after percutaneous coronary intervention.
      Cardiovascular magnetic resonance imaging was performed 5 +/- 2 and 104 +/- 11
      days after admission. Using k-means cluster analysis, 3 CMR risk groups for LV
      dysfunction (low LV ejection fraction at baseline and follow-up) were identified
      based on combinations of infarct size (IS), infarct transmurality, and
      microvascular obstruction. Stepwise discriminant analysis was used to determine
      which STR variable best discriminated between CMR risk groups. RESULTS: Baseline
      LV ejection fraction improved in all groups but remained lowest in the high-risk
      group (41% +/- 7% and 44% +/- 6%), as compared with the intermediate (51% +/- 5%
      and 56% +/- 5%) and low-risk groups (56% +/- 7% and 58% +/- 5%). Infarct size was
      significantly different among the groups (34% +/- 5%, 19% +/- 4%, and 6% +/- 4%;
      P < .001) and mainly determined the effect on LV dysfunction. Of all STR
      variables, worst lead residual ST deviation 30 minutes after reperfusion
      accurately discriminated between the high- and combined low-/intermediate risk
      groups. CONCLUSION: Worst lead residual ST deviation 30 minutes after reperfusion
      allows accurate identification of patients at high risk for LV dysfunction, which
      was mainly related to IS rather than transmurality or microvascular obstruction.

PMID- 21872004
TI  - Modeling vectorcardiograms based on left ventricle papillary muscle position.
AB  - BACKGROUND: Vectorcardiographic QRS loops illustrate the electrical activation of
      the left ventricle (LV) in 3-dimensional space; however, the individual
      variability in these loops is not well understood. The left bundle-branch fan
      distributes the initial activation to the LV and has been shown to distribute its
      fascicles between the LV papillary muscles. Computer models of LV activation
      using papillary muscle as the initial electrical activation points accurately
      predict QRS duration and frontal plane axis. METHODS: Twelve healthy adults
      received standard 12-lead electrocardiograms and 1.5-T cardiac magnetic resonance
      imaging. A software developed by ECG-TECH Corp (Huntington Station, NY) generated
      3-dimensional QRS vector loops for each subject. Short- and long-axis papillary
      muscle positions were measured for each subject using cardiac magnetic resonance
      images. A theoretical plane equidistant from the endocardial origins of each
      papillary muscle was constructed. Vectors perpendicular to the QRS vector loop
      and the theoretical plane termed the plane identifier were used for comparison.
      Spearman rank correlation was used to compare the azimuth and elevation of the
      plane identifiers of the QRS vector loop and the theoretical plane. RESULTS: No
      correlation was found between the azimuth or elevation of the theoretical plane
      and the QRS vector loops with Spearman rank correlation coefficients of rho =
      0.11 (P = .71) and rho = 0.22 (P = .49), respectively. Subgroup analysis by QRS
      vector loop morphology (planar vs nonplanar, narrow vs wide) also demonstrated no
      correlation. CONCLUSIONS: Modeling the activation of the LV based on papillary
      muscle position alone may be overly simplistic. Better understanding of what
      other factors contribute to individual variation in LV activation will help
      develop a more useful theoretical model.

PMID- 21872005
TI  - Repolarization changes in patients with heart failure receiving cardiac
      resynchronization therapy-signs of cardiac memory.
AB  - BACKGROUND AND PURPOSE: Cardiac memory is known as T-wave inversions and other
      repolarization changes after a period of altered ventricular activation,
      previously mainly studied in structurally normal hearts. We investigated
      repolarization changes in failing hearts undergoing cardiac resynchronization
      therapy (CRT). METHODS: Electrocardiogram and vectorcardiogram were recorded
      before and 1 day and 2 weeks after initiation of CRT in 23 patients with heart
      failure and left bundle-branch block. RESULTS: After 1 day of CRT, the T vector
      during intrinsic conduction (left bundle-branch block) had rotated toward the
      direction of the paced QRS vector; T-vector size had increased with further
      increase after 2 weeks (T-vector amplitude, 889 +/- 277 vs 651 +/- 225 MUV; T
      area, 169 +/- 70 vs 102 +/- 39 MUVs; P < .01) accompanied by prolonged
      repolarization (T peak-to-end, 174 +/- 34 vs 127 +/- 16; QT interval corrected
      for heart rate, 541 +/- 59 vs 493 +/- 33 milliseconds; P < .01). CONCLUSIONS:
      Repolarization changes are present in patients with heart failure, although less
      pronounced compared with after right ventricular pacing in structurally normal
      hearts.

PMID- 21872006
TI  - Is a new approach to Analytical Chemistry possible?

PMID- 21872007
TI  - Advances in Analytical Chemistry benefit science and society.

PMID- 21872008
TI  - Phospholipidomic identification of potential plasma biomarkers associated with
      type 2 diabetes mellitus and diabetic nephropathy.
AB  - Type 2 diabetes mellitus (T2DM) and its attendant complications, such as diabetic
      nephropathy (DN), impose a significant societal and economic burden. The
      investigation of discovering potential biomarkers for T2DM and DN will facilitate
      the prediction and prevention of diabetes. Phospholipids (PLs) and their
      metabolisms are closely allied to nosogenesis and aggravation of T2DM and DN. The
      aim of this study is to characterize the human plasma phospholipids in T2DM and
      DN to identify potential biomarkers of T2DM and DN. Normal phase liquid
      chromatography coupled with time of flight mass spectrometry (NPLC-TOF/MS) was
      applied to the plasma phospholipids metabolic profiling of T2DM and DN. The
      plasma samples from control (n=30), T2DM subjects (n=30), and DN subjects (n=52)
      were collected and analyzed. The significant difference in metabolic profiling
      was observed between healthy control group and DM group as well as between
      control group and DN group by the help of partial least squares discriminant
      analysis (PLS-DA). PLS-DA and one-way analysis of variance (ANOVA) were
      successfully used to screen out potential biomarkers from complex mass
      spectrometry data. The identification of molecular components of potential
      biomarkers was performed on Ion trap-MS/MS. An external standard method was
      applied to quantitative analysis of potential biomarkers. As a result, 18
      compounds in 7 PL classes with significant regulation in patients compared with
      healthy controls were regarded as potential biomarkers for T2DM or DN. Among
      them, 3 DM-specific biomarkers, 8 DN-specific biomarkers and 7 common biomarkers
      to DM and DN were identified. Ultimately, 2 novel biomarkers, i.e., PI C18:0/22:6
      and SM dC18:0/20:2, can be used to discriminate healthy individuals, T2DM cases
      and DN cases from each other group.

PMID- 21872009
TI  - Determination of sugars in depilatory formulations: a green analytical method
      employing infrared detection and partial least squares regression.
AB  - A green analytical method was developed for the analysis of sugar-based
      depilatories. Three independent partial least squares (PLS) regression models
      were built for the direct determination of glucose, fructose and maltose without
      any sample pretreatment based on their attenuated total reflectance - Fourier
      transform infrared (ATR-FTIR) spectra. The models showed adequate prediction
      capabilities with root-mean-square-errors of prediction ranging from 7.04 to
      12.55 mg sugar g(-1) sample. As a reference procedure, gradient liquid
      chromatography with on-line infrared detection, employing background correction
      based on cubic smoothing splines, was used. The analysis revealed changes in the
      sugar concentration due to the formulation process as compared to information on
      the ingredients provided by the manufacturers. Although fructose, glucose and
      sucrose were declared to be used for the production of depilatories, in the final
      products only fructose, glucose and maltose were determined. This fact was
      attributed to pH and temperature conditions employed during the production
      process as well as to the use of glucose syrup instead of crystalline glucose.
      The present ATR-FTIR-PLS method enables an accurate, cheap and fast determination
      without solvent consumption or toxic waste generation and offers therefore a
      green screening alternative to methods employing chromatographic techniques.

PMID- 21872010
TI  - Flow injection fluorometric determination of ascorbic acid using perylenebisimide
      linked nitroxide.
AB  - A simple and sensitive flow injection fluorometric method for the determination
      of ascorbic acid is described. Perylenebisimide-linked nitroxide (PBILN) is used
      as a fluorescent reagent, which permits the selective determination of ascorbic
      acid. The fluorescence of the perylenebisimide moiety in PBILN is quenched by the
      nitroxide moiety, which is linked to the perylenebisimide. When a stream of a
      solution of ascorbic acid is merged with a stream of PBILN, the ascorbic acid
      reacts with the nitroxide moiety of PBILN to form hydroxylamine, and the
      fluorescence properties of the perylenebisimide moiety are recovered. As a
      result, a peak-shaped fluorescence signal is produced, which can be observed by a
      fluorescence detector located downstream. Under optimized conditions, a good
      linear relationship between the concentration of ascorbic acid and peak height in
      the concentration range from 0.5 to 10 MUmol L(-1) was found and the detection
      limit (S/N=3) was 0.28 MUmol L(-1). The relative standard deviation for the
      determination of 4.0 MUmol L(-1) ascorbic acid samples was 1.0% (n=5). The
      proposed method was applied to the determination of ascorbic acid in several soft
      drink beverages and the analytical results were in good agreement with those
      obtained using a conventional method.

PMID- 21872011
TI  - Establishing the detection threshold for Bacillus subtilis in a complex matrix
      using an inorganic fingerprint approach.
AB  - Methods for the detection and characterization of airborne biological warfare
      agents, such as bacteria, using their DNA or organic composition are fairly well
      developed. This approach is useful for identifying the type of bacterial strain
      once the organism has been isolated from the matrix sampled (e.g., dust
      particles) and can identify genetically related organisms, which might be helpful
      during a forensic investigation. However, this genetic signature will not reveal
      information related to the methods used to grow and weaponize the organism.
      Bacteria will take on an inorganic signature that is related to their growth and
      processing history. Therefore, the ability to characterize the inorganic
      fingerprint of a biological particle has the potential to detect the presence of
      a bio-agent and expand the forensic tools available to those investigating the
      origin of biological weapons. This investigation builds on previous work
      documenting the usefulness of the inorganic fingerprint and evaluates the limits
      of detection in the presence of background dust. Based on ICP-MS measurements and
      mixing models of digested mixtures of laboratory cultured Bacillus subtilis
      (anthrax stimulant) and NIST Standard Reference Material 2709 (dust stimulant),
      the inorganic fingerprint method is capable of detecting toxicologically relevant
      levels of a bio-warfare agent in the presence of a complex background matrix.

PMID- 21872012
TI  - Facile synthesis of N-acetyl-L-cysteine capped ZnS quantum dots as an eco
      friendly fluorescence sensor for Hg2+.
AB  - This paper described an investigation of a novel eco-friendly fluorescence sensor
      for Hg(2+) ions based on N-acetyl-l-cysteine (NAC)-capped ZnS quantum dots (QDs)
      in aqueous solution. By using safe and low-cost materials, ZnS QDs modified by
      NAC were easily synthesized in aqueous medium via a one-step method. The
      quantitative detection of Hg(2+) ions was developed based on fluorescence
      quenching of ZnS QDs with high sensitivity and selectivity. Under optimal
      conditions, its response was linearly proportional to the concentration of Hg(2+)
      ions in a range from 0 to 2.4 * 10(-6) mol L(-1) with a detection limit of 5.0 *
      10(-9) mol L(-1). Most of common physiologically relevant cations and anions did
      not interfere with the detection of Hg(2+). The proposed method was applied to
      the trace determination of Hg(2+) ions in water samples. The possible quenching
      mechanism was also examined by fluorescence and UV-vis absorption spectra.

PMID- 21872013
TI  - Evaluation of grinding methods for pellets preparation aiming at the analysis of
      plant materials by laser induced breakdown spectrometry.
AB  - It has been demonstrated that laser induced breakdown spectrometry (LIBS) can be
      used as an alternative method for the determination of macro (P, K, Ca, Mg) and
      micronutrients (B, Fe, Cu, Mn, Zn) in pellets of plant materials. However,
      information is required regarding the sample preparation for plant analysis by
      LIBS. In this work, methods involving cryogenic grinding and planetary ball
      milling were evaluated for leaves comminution before pellets preparation. The
      particle sizes were associated to chemical sample properties such as fiber and
      cellulose contents, as well as to pellets porosity and density. The pellets were
      ablated at 30 different sites by applying 25 laser pulses per site (Nd:YAG@1064
      nm, 5 ns, 10 Hz, 25J cm(-2)). The plasma emission collected by lenses was
      directed through an optical fiber towards a high resolution echelle spectrometer
      equipped with an ICCD. Delay time and integration time gate were fixed at 2.0 and
      4.5 MUs, respectively. Experiments carried out with pellets of sugarcane, orange
      tree and soy leaves showed a significant effect of the plant species for choosing
      the most appropriate grinding conditions. By using ball milling with agate
      materials, 20 min grinding for orange tree and soy, and 60 min for sugarcane
      leaves led to particle size distributions generally lower than 75 MUm. Cryogenic
      grinding yielded similar particle size distributions after 10 min for orange
      tree, 20 min for soy and 30 min for sugarcane leaves. There was up to 50%
      emission signal enhancement on LIBS measurements for most elements by improving
      particle size distribution and consequently the pellet porosity.

PMID- 21872014
TI  - Trace analysis of acidic pharmaceutical residues in waters with isotope dilution
      gas chromatography-mass spectrometry via methylation derivatization.
AB  - Acidic pharmaceutical residues are pollutants of emerging concern and are
      generally monitored by HPLC-MS/MS. However, due to the limited separation
      efficiency of HPLC column and lack of suitable mass transition for confirmation
      analysis, some interference may not be separated completely and differentiated
      from ibuprofen, which may cause the results with interference, especially in
      sample with complex matrix. The objective of this study is to develop a sensitive
      and reliable method for the determination of acidic pharmaceutical residues in
      water samples by GC-MS with better resolution by using methylation derivatization
      and isotope dilution techniques. TMSDM, a mild reagent, was used as the
      derivatization reagent coupling with the isotope dilution technique, for the
      first time, to improve the precision and accuracy of the analytical method to
      determine the pharmaceutical residues in water. The MDLs for the five acidic
      organic compounds: ibuprofen, gemfibrozil, naproxen, ketoprofen and diclofenac
      were from 0.7 to 1.1 ng/L, with recoveries ranging from 93 to 110%. Alternative
      to the HPLC-MS/MS method, the developed GC-MS protocols provides an additional
      option for the analysis of acidic pharmaceutical residues in water, with better
      separation efficiency in reducing interferences from complicated sample matrix,
      for determination of ibuprofen residues.

PMID- 21872015
TI  - Nanoliter droplet array for microRNA detection based on enzymatic stem-loop
      probes ligation and SYBR Green real-time PCR.
AB  - In this paper, a nanoliter droplet array based on enzymatic stem-loop probes
      ligation and SYBR Green real-time PCR for quantification of microRNA was
      developed. By employing T4 RNA ligase 2 instead of T4 DNA ligase, we designed
      simplified stem-loop probes to perform microRNA-templated DNA ligation and
      reduced the non-specific ligation of T4 DNA ligase. SYBR green I dye was employed
      instead of TaqMan probes in present miniaturized real-time PCR systems.
      Specifically, we optimized the dosage of SYBR Green I dye in nanoliter droplet
      and verified the performance of this system by detecting synthetic mir-122 with a
      6 logs dynamic range (from 1.5 * 10(5) to 1.5 * 10(10) copies). Linear
      relationship of the standard curve (R(2)=0.9997) and high PCR amplification
      efficiency (96.83%) were obtained under the optimized conditions. We detected the
      expression of mir-122 across five mouse tissues and the result was consistent
      with that TaqMan microRNA assay. We think this miniaturized real-time PCR
      platform reduced the detection cost considerably, thus showing the great
      potential to quantitative biology.

PMID- 21872016
TI  - A quick analytical method using direct solid sample introduction and GC-ECD for
      pesticide residues analysis in crops.
AB  - In this work, an analytical method for GC using direct solid sample introduction
      was developed to tackle the problem regarding quick detection of pesticide
      residue in crops and large-scale screening of samples. 10mg of the crop solid
      sample without sample pre-treatment was directly introduced into a modified
      split/splitless injector for GC analysis. A split/splitless injector was modified
      to quickly remove oxygen and low boiling-point matrices of the sample. The whole
      sampling procedure was simple and it required less than 5 min. The experimental
      parameters including injector-port temperature, removal of oxygen and low boiling
      point matrices, size and the amount of the solid sample, oven temperature program
      were studied. Satisfactory recoveries of 6 pesticides (methyl parathion,
      fenitrothion, aldrin, dieldrin, endosulfan, o,p'-DDT) were obtained in maize and
      rice sample. Relative standard deviation was less than 15%. Experimental results
      showed that the proposed method was quick and reliable for pesticide residues
      analysis in crops.

PMID- 21872017
TI  - Determination of 232Th in seawater by ICP-MS after preconcentration and
      separation using a chelating resin.
AB  - This article describes an analytical method for the separation, preconcentration
      and determination of (232)Th in seawater samples at sub-ng/L levels using a
      NOBIAS CHELATE PA1 resin and a sector field (SF) inductively coupled plasma mass
      spectrometer (ICP-MS). The resin showed excellent adsorption of (232)Th at a low
      pH of 2.4 +/- 0.4 in a relatively small volume (200 mL) of seawater. (232)Th
      adsorbed on the resin was easily eluted using 5 mL of 0.8M HNO(3). An enrichment
      factor of 40 was achieved for (232)Th analysis. Ethylenediamine-tetraacetic acid
      disodium salt dehydrate (EDTA) was used to investigate the effect of (232)Th
      binding organic ligand on the retention of (232)Th on the chelating resin.
      Results obtained using acidified samples (pH of 2.4 +/- 0.4) showed EDTA had no
      significant effect on (232)Th recovery, indicating that at this low pH, (232)Th
      was dissociated from the (232)Th-binding organic ligand and quantitatively
      retained on the NOBIAS CHELATE PA1 resin. The developed analytical method was
      characterized by a separation and preconcentration taking approximately 4h and a
      low detection limit of 0.0038 ng/L for (232)Th, and was successfully applied to
      the determination of (232)Th in seawater samples collected from coastal areas,
      Japan.

PMID- 21872018
TI  - Biodegradation analyses of trichloroethylene (TCE) by bacteria and its use for
      biosensing of TCE.
AB  - Trichloroethylene (TCE) is a toxic, recalcitrant groundwater pollutant. TCE
      degrading microorganisms were isolated from various environments. The aerobic
      bacteria isolated from toluene- and tryptophan-containing media were Pseudomonas
      sp. strain ASA86 and Burkholderia sp. strain TAM17, respectively; these are
      necessary for inducing TCE biodegradation in a selective medium. The half
      degradation time of TCE to a concentration of 1mg/L was 18 h for strain ASA86 and
      7 days for strain TAM17. While identifying toluene/TCE degradation genes, we
      found that in strain ASA86, the gene was the same as the todC1 gene product
      encoding toluene dioxygenase identified in Pseudomonas putida F1, and that in
      strain TAM17, the gene was similar to the tecA1 gene product encoding
      chlorobenzene dioxygenase identified in Burkholderia sp. PS12. A novel TCE
      biosensor was developed using strain ASA86 as the inducer of toluene under
      aerobic conditions. The TCE biosensor exhibited a linear relationship below 3 ppm
      TCE. Detection limit of the biosensor was 0.05 ppm TCE. The response time of the
      biosensor was less than 10 min. The biosensor response displayed a constant level
      during a 2 day period. The TCE biosensor displayed sufficient sensitivity for
      monitoring TCE in environmental systems.

PMID- 21872019
TI  - Application of an unusual ninhydrin-based reaction for the indirect chiral
      resolution of D,L-penicillamine.
AB  - An unusual reaction involving ninhydrin and aminothiols was exploited to set an
      indirect method for the chiral recognition of stereoisomers of penicillamine.
      Separation of diastereoisomers was achieved on a C18 column in isocratic mode by
      using a mixture of propionic acid (pH 3.0)/acetonitrile/water (10:10:80, v/v/v)
      as a mobile phase. Diastereoisomers were detected by a fluorescence detector in
      fairly short times (about 7 min) and with a good resolution. The lowest
      detectable amount of toxic isomer of penicillamine (l-enantiomer) in samples of
      the d-enantiomer, was around 0.01%. The method was also suitable for the indirect
      chiral recognition of other aminothiols such as cysteine and cysteinylglycine.

PMID- 21872020
TI  - Indium determination using slotted quartz tube-atom trap-flame atomic absorption
      spectrometry and interference studies.
AB  - Sensitivity enhancement of indium determination by flame atomic absorption
      spectrometry (FAAS) was achieved; using a slotted quartz tube (SQT-FAAS) and
      slotted quartz tube atom trap (SQT-AT-FAAS). SQT was used as an atom trap (AT)
      where the analyte is accumulated in its inner wall prior to re-atomization. The
      signal is formed after re-atomization of analyte on the trap surface by
      introduction of 10 MUL of isobutyl methyl ketone (IBMK). Sensitivity was improved
      400 times using SQT-AT-FAAS system with respect to conventional FAAS and 279
      times with respect to SQT-FAAS without any collection. Characteristic
      concentration (C(0)) and limit of detection values were found to be 3.63 ng mL(
      1) and 2.60 ng mL(-1), respectively, using a sample flow rate of 7.0 mL min(-1)
      and a collection period of 5.0 min. In addition, interference effects of some
      elements on indium signal were studied. In order to characterize indium species
      trapped, X-ray Photoelectron Spectrometry (XPS) was utilized and it was found
      that indium was collected on the inner surface of SQT as In(2)O(3). The accuracy
      of the procedure was checked to determine indium in the standard reference
      material (Montana Soil, SRM 2710).

PMID- 21872021
TI  - Atmospheric pressure ion focusing with a vortex stream.
AB  - For successful operation of ionization analysis techniques an efficient sampling
      and sample ion transportation into an analytical path are required. This is of
      particular importance for atmospheric pressure ionization sources like corona
      discharge, electrospray, MALDI, ionization with radioactive isotopes ((3)H,
      (63)Ni) that produce nonuniform spatial distribution of sample ions. The
      available methods of sample ion focusing with electric fields are either
      efficient at reduced pressure (to 1 Torr) or feature high sample losses. In this
      paper we suggest to use a highly whirled gas stream for atmospheric pressure ion
      focusing. We use a (63)Ni radioactive source to produce an ionized bipolar sample
      at atmospheric pressure. It is shown by experiments that compared to an
      aspiration method a forced highly whirled vortex stream allows one to enhance the
      efficiency of remote ionized sample collection at distances equal to the vortex
      sampler diameter by an order of magnitude. With a vortex stream, a sixfold
      increase in the efficiency of the radial ionized sample collection has been
      obtained. It may be deduced that with the vortex stream remote sampling obtains a
      new feature which is characterized by a considerable enhancement of the
      efficiency of the ionized sample collection and can be called as a "gas-dynamic"
      ionized sample focusing. Considered is the effect of recombination losses of the
      ionized sample during the remote sampling thereof with the vortex sampler.
      Prospects for a practical implementation of the vortex sampler for solving the
      problems of the customs control over the smuggling of radioactive alpha and beta
      sources are made based on the research results.

PMID- 21872022
TI  - Protonation and ion exchange equilibria of weak base anion-exchange resins.
AB  - Protonation and ion exchange equilibria of weak base anion-exchange resins, in
      which tertiary amine moieties were introduced as a functional group, were
      investigated by applying NMR spectroscopy to species adsorbed into the resins.
      (31)P NMR signals of the phosphinate ion in the resin phases shifted to a lower
      field due to the influence of protonation of the tertiary amine groups of the
      resins in the pH range of 4-10. Protonation constants of the tertiary amine
      groups in styrene-divinylbenzene (DVB)-based resins were estimated to be
      K(H)=10(6.4) for Amberlite IRA96 and 10(6.5) for DIAION WA30 by the (31)P NMR
      method using the phosphinate ion as a probe species. In addition to the low field
      shift caused by the protonation of the tertiary amine moieties, another low field
      shift was observed for the phosphinate ion in acrylic acid-DVB-based resins at a
      rather high pH. This shift should be due to an unexpected deprotonation in the
      acrylic resin: a tautomerism accompanying the proton release from the amide form
      to the imide one in the functional group, thus, the resin could exhibit a cation
      exchange property at the high pH. Protonation constants of the tertiary amine
      moieties in the acrylic resins were estimated to be 10(8.8) for DIAION WA10,
      10(9.0) for Amberlite IRA67 and 10(9.3) for Bio-Rad AG 4-X4 on the basis of the
      Henderson-Hasselbalch equation using the resin phase pH estimated by the (133)Cs
      and (1)H NMR signal intensities.

PMID- 21872023
TI  - Room-temperature fluorescence spectroscopy of monohydroxy metabolites of
      polycyclic aromatic hydrocarbons on octadecyl extraction membranes.
AB  - Urine analysis of monohydroxy metabolites is recognized as an accurate assessment
      of human exposure to polycyclic aromatic hydrocarbons. Despite the sophisticated
      arsenal of analytical tools, monitoring of monohydroxy metabolites via simple,
      cost effective and direct methods of analysis still remains a challenge. This
      article evaluates the analytical potential of solid-phase extraction room
      temperature fluorescence spectroscopy for the problem at hand. Extraction
      membranes serve the dual purpose of sample pre-concentration and solid substrate
      for RTF measurements. The potential of our proposition is demonstrated with the
      analysis of 2-hydroxy-fluorene, 1-hydroxy-pyrene, 3-hydroxy-benzo[a]pyrene and 9
      hydroxy-phenanthrene in synthetic urine samples. Signal reproducibility is
      improved with the aid of a sample holder specifically designed for the manual
      optimization of luminescence signals. Background correction of solid substrates
      is carried out with the aid of Asymmetric Least Squares. Recovery values for the
      studied metabolites varied from 99.0 +/- 1.2% (3-hydroxy-benzo[a]pyrene) to 99.9
      +/- 0.05% (1-hydroxy-pyrene). With only 10 mL of urine sample, the limits of
      detection varied from 57 pg mL(-1) (2-hydroxy-fluorene) to 2 pg mL(-1) (1-hydroxy
      pyrene). Additional figures of merit include a simple experimental procedure for
      routine screening of numerous samples and compatibility with portable
      instrumentation for field analysis. Because of the non-destructive nature of
      fluorescence measurements, membranes can be brought to the lab for subsequent
      elution and confirmation of compounds via high-resolution techniques.

PMID- 21872024
TI  - A novel piezoelectric immunosensor for the detection of malarial Plasmodium
      falciparum histidine rich protein-2 antigen.
AB  - A novel piezoelectric (PZ) immunosensor for the direct detection of malarial
      Plasmodium falciparum histidine rich protein-2 (PfHRP-2) antigen was developed.
      The mixed self-assembled monolayers (SAMs) of thioctic acid and 1-dodecanethiol
      were formed on gold surface of quartz crystal. Cyclic voltammetry,
      electrochemical impedance spectroscopy and surface Raman spectroscopy techniques
      were used to characterize the mixed SAMs. The rabbit anti-PfHRP-2 antibodies were
      coupled on mixed SAM modified gold surface of quartz crystal via NHS/EDC
      activation method. The PZ immunosensor was applied to detect PfHRP-2 in the
      linear range of 15-60 ng/ml with a detection limit of 12 ng/ml. It was also found
      that even after 14 days of storage, 50% of the activity still remained. Clinical
      human serum samples were tested with this method, and the results were in
      agreement with those obtained from commercially available ICT kit (NOW((r))
      Malaria).

PMID- 21872025
TI  - A novel fiber optic spectrophotometric determination of nitrite using Safranin O
      and cloud point extraction.
AB  - A novel fiber optic spectrophotometric method for nitrite determination in
      different samples is suggested, based on the reaction of nitrite with Safranin O
      in acidic medium to form a diazo-safranin, which is subsequently coupled with
      pyrogallol in alkaline medium to form a highly stable, red azo dye, followed by
      cloud point extraction (CPE) using a mixed micelle of a nonionic surfactant,
      Triton X-114, with an anionic surfactant, sodium dodecyl sulphate (SDS). The
      reaction and extraction conditions (e.g., acidity for diazotization and
      alkalinity for pyrogallol coupling, and other reagent concentrations, time, and
      tolerance to other ions) were optimized. Linearity was obeyed in a concentration
      range up to 230 MUg L(-1), and the detection limit of the method is 0.5 MUg L(-1)
      of nitrite ion. The molar absorptivity for nitrite of the Safranin-diazonium salt
      (E(610 nm) =4 * 10(3) L mol(-1)cm(-1)) existing in literature was greatly
      enhanced by pyrogallol coupling and CPE enrichment (E(592 nm)=1.39 * 10(5) L mol(
      1)cm(-1)). The method was applied to the determination of nitrite in tap water,
      lake water and milk samples with an optimal preconcentration factor of 20.

PMID- 21872026
TI  - Determination of various estradiol mimicking-compounds in sewage sludge by the
      combination of microwave-assisted extraction and LC-MS/MS.
AB  - In this work, we present the development and application of a microwave assisted
      extraction followed by liquid chromatography-tandem mass spectrometry methodology
      (MAE-LC-MS/MS) for the determination of various estradiol-mimicking compounds in
      sewage sludge samples. For the purification of the MAE extracts, we have employed
      a solid phase extraction (SPE) clean-up procedure, previously optimised. The
      entire method provides recoveries between 71.7% and 103.1%, with relative
      standard deviation lower than 11.1% and limits of detection ranging from 0.6 to
      3.5 ng g(-1). The developed method was applied to samples from three wastewater
      treatment plants (WWTPs) located in Las Palmas of Gran Canaria (Spain), two of
      which had a conventional activated sludge treatment (AST), whereas the third
      treatment plant had an advanced membrane bioreactor treatment (MBR). All of the
      analytes in the study, including (nonylphenol (NP), octylphenol (OP), and some of
      their ethoxylated chains AP(n)EOs (n <= 7), 17beta-estradiol (E2), estriol (E3),
      17alpha-ethynylestradiol (EE) and bisphenol-A (BPA)), were found in almost all
      samples in concentrations ranging from 0.9 to 710.2 ng g(-1).

PMID- 21872027
TI  - Optimization and application of microwave-assisted acid hydrolysis for rapid
      quantification of protein oxidation markers using LC-MS.
AB  - Simple and efficient microwave-assisted acid hydrolysis (MAAH) of proteins was
      used for rapid quantification of alpha-aminoadipic semialdehyde (AAS) and gamma
      glutamic semialdehyde (GGS) as major protein oxidation markers. The precursor
      amino acid residues corresponding to AAS and GGS in oxidized proteins were
      derivatized by reductive amination with sodium cyanoborohydride (NaCNBH(3)) and p
      aminobenzoic acid (ABA) followed by MAAH to generate the marker derivatives AAS
      ABA and GGS-ABA. The quantification was performed using electrospray ionization
      liquid chromatography-mass spectrometry (ESI LC-MS). The important parameters for
      hydrolysis were optimized, which include the temperature, the reaction time, the
      acid concentration and volume as well as the microwave power. Compared to the
      conventional acid hydrolysis of 18-24h using 6-12 M HCl at 110 degrees C applied
      commonly in the literature and also in this work, MAAH of proteins can be
      completed as fast as in only 2-10 min and, additionally, with a 3-5 times higher
      yield of the final derivatization products. Furthermore, a better agreement
      between the ratio of the detected derivatization products and the theoretical
      yields from the studied protein has also been achieved, which indicates that MAAH
      may serve as a more reliable method of acid hydrolysis for this purpose than that
      with conventional thermal heating. The MAAH method is demonstrated to be a time
      saving, reproducible and efficient technique for studying AAS and GGS as protein
      oxidation markers using LC-MS.

PMID- 21872028
TI  - On-line coupling of automatic solid-phase extraction and HPLC for determination
      of carotenoids in serum.
AB  - The automated method developed for the determination of carotenoids uses 200 MUL
      of serum, which was mixed with 400 MUL of tetrahydrofuran, vortexed for 1 min,
      settled for 10 min, centrifuged for 6 min and the supernatant injected into an
      automatic solid-phase extraction (SPE) system for cleanup-preconcentration. A 10%
      water-acetonitrile mobile phase at 1.5 mL min(-1) eluted the retained compounds
      and transferred them on-line to a reversed-phase analytical column for individual
      separation of the target analytes. Visible detection was performed at 450 and 460
      nm. The detection limits for the target analytes were between 3 and 30 ng mL(-1);
      the precision (expressed as relative standard deviation) ranged between 2.83 and
      5.06% for repeatability and between 3.80 and 7.40% for within laboratory
      reproducibility. The total analysis time was 18 min. The proposed method is
      reliable, robust, and has an excellent potential for high-throughput use in both
      clinical and research laboratories.

PMID- 21872029
TI  - Determination of benzophenones in human placental tissue samples by liquid
      chromatography-tandem mass spectrometry.
AB  - Benzophenones (BPs) are a family of compounds widely used to protect the skin and
      hair from UV irradiation. Despite human exposure to BPs through dermal
      application of products containing sunscreen agents and the increasing evidence
      that BPs are able to interfere with endocrine systems, few studies have examined
      the occurrence of BPs in humans. In this work, we propose a new liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method to determine six BPs,
      namely, benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3),
      benzophenone-6 (BP-6), benzophenone-8 (BP-8) and 4-hydroxybenzophenone (4-OH-BP)
      in human placental tissue samples. The method involves an extraction step of the
      analytes from the samples using ethyl acetate, followed by a clean-up step using
      centrifugation prior to their quantification by LC-MS/MS using an atmospheric
      pressure chemical ionization (APCI) interface in the positive mode. Benzophenone
      d(10) (BP-d(10)) was used as surrogate. Found detection limits (LOD) ranged from
      0.07 to 0.3 ng g(-1) and quantification limits (LOQ) from 0.3 to 1.0 ng g(-1),
      while inter- and intra-day variability was under 5%. The method was validated
      using standard addition calibration and a recovery assay. Recovery rates for
      spiked samples ranged from 98 to 104%. This method was satisfactorily applied for
      the determination of BPs in 16 placental tissue samples collected from women who
      live in Granada (Spain).

PMID- 21872030
TI  - Multiresidue determination of 160 pesticides in wines employing mixed-mode
      dispersive-solid phase extraction and gas chromatography-tandem mass
      spectrometry.
AB  - A new multiresidue method for the efficient screening, identification and
      quantification of over 160 pesticides belonging to different chemical classes in
      red, rose and white wines have been developed. The analysis was based on gas
      chromatographic-tandem quadrupole mass spectrometric determination (GC-QqQ
      MS/MS). An optimization strategy involved the selection of buffering conditions
      and sorbents for dispersive-solid phase extraction (dispersive-SPE) in order to
      achieve acceptably high recoveries and reduce co-extractives in the final
      extracts. As a result, the optimized procedure allowed us to obtain consistent
      recoveries of the target pesticides including problematic ones such as captan,
      chlorothalonil, dichlofluanid, folpet and tolylfluanid. The attained recoveries
      were typically between 80 and 110% (89% on average) with RSD values typically
      lower than 10% (8% on average) at three spiking levels of 0.01, 0.05 and 0.2 mg
      kg(-1). Linearity was studied in the range between 0.005 and 0.2 mg kg(-1) using
      pesticide standards prepared both in pure solvent and in the presence of matrix,
      showing coefficients of determination (R(2)) higher than 0.99 for all the
      pesticides except for desmedipham, thiabendazole and thiamethoxam in pure
      solvent. The study of the ratio of the slopes obtained in solvent and in matrix
      provided information about the matrix effects, which was <10%, 10-20% and >20%
      for 33, 36 and 31% of the studied pesticides, respectively. To improve accuracy,
      matrix matched standards were always used for calculation of the quantification
      results. The expanded uncertainties were estimated by using a "top-down" approach
      as being 17% on average (coverage factor k=2, confidence level 95%). Finally, the
      method was used with success to detect and quantify pesticide residues in
      commercial wines.

PMID- 21872031
TI  - Gold nanoparticles-based catalysis for detection of S-nitrosothiols in blood
      serum.
AB  - Accumulating evidence suggests that S-nitrosothiols (RSNOs) play key roles in
      human health and disease. To clarify their physiological functions and roles in
      diseases, it is necessary to promote some new techniques for quantifying RSNOs in
      blood and other biological fluids. Here, a new method using gold nanoparticle
      catalysts has been introduced for quantitative evaluation of RSNOs in blood
      serum. The assay involves degrading RSNOs using gold nanoparticles and detecting
      nitric oxide (NO) released with NO-selective electrodes. The approach displays
      very high sensitivity for RSNOs with a low detection limit in the picomolar
      concentration range (5.08 * 10(-11) mol L(-1), S/N=3) and is free from
      interference of some endogenous substances such as NO(2)(-) and NO(3)(-) co
      existing in blood serum. A linear function of concentration in the range of (5.0
      1000.0) * 10(-9) mol L(-1) has been observed with a correlation coefficient of
      0.9976. The level of RSNOs in blood serum was successfully determined using the
      described method above. In addition, a dose-dependent effect of gold
      nanoparticles on the sensitivity for RSNOs detection is revealed, and thereby the
      approach is potentially useful to evaluate RSNOs levels in various biological
      fluids via varying gold nanoparticles concentration.

PMID- 21872032
TI  - Benzodipyrrole derivates as new ionophores for anion-selective electrodes:
      improving potentiometric selectivity towards divalent anions.
AB  - Two open substituted benzodipyrroles were tested as hydrogen-bond-forming anion
      ionophores for the development of anion-selective electrodes. These compounds
      were incorporated in plasticized polymeric membranes with different plasticizers,
      using different membrane compositions to explore their response towards several
      anions. The electrodes constructed with membranes containing 2-nitrophenyl octyl
      ether and a 0.5 molar ratio ionic additive/ionophore showed pronounced anti
      Hofmeister behaviour, providing a significantly enhanced response towards the
      divalent anions sulfate, sulfite, thiosulfate and oxalate. The selected
      electrodes were also evaluated in terms of detection limits and selectivity. (1)H
      NMR experiments were carried out in an attempt to explain some aspects of the
      behaviour observed.

PMID- 21872033
TI  - Structural and functional characterisation of a biohybrid material based on
      acetylcholinesterase and layered double hydroxides.
AB  - This work describes the use of layered double hydroxides (LDHs) for the
      immobilisation of acetylcholinesterase (AChE) on insulator/semiconductor solid
      supports. Different LDHs have been synthesised by a co-precipitation method.
      Afterwards, biohybrid materials based on AChE-LDH mixtures have been produced
      using wild and recombinant enzymes. Spectroscopic techniques have confirmed the
      LDH phase identity and the links created between the LDH and AChE.
      Spectrophotometric assays have demonstrated that most of the biohybrid materials
      are functional and stable. Several configurations have been used for AChE
      immobilisation. The highest catalytic responses have been observed when using
      wild enzyme and immobilising AChE-LDH mixtures on LDHs previously deposited on
      the solid supports. LDHs have been demonstrated to be suitable host matrices for
      AChE immobilisation on electrodes for the subsequent development of
      electrochemical biosensors.

PMID- 21872034
TI  - Electrochemical speciation of dissolved Cu, Pb and Zn in an estuarine ecosystem
      (Ria de Vigo, NW Spain): comparison between data treatment methods.
AB  - The total concentration and chemical speciation of Cu, Pb and Zn were determined
      by square wave anodic stripping voltammetry (SWASV) in the Ria de Vigo, an
      estuarine area located in NW Spain. Surface and bottom waters from 6 locations
      were collected in two seasons during 3 years. The total Pb was below 1 nM, and Cu
      and Zn concentrations, ranged from 3 to 44 nM and from 9 to 300 nM respectively.
      A gradient from sampling points located in the port of Vigo to external areas was
      observed. The speciation of the metals (ligand concentration and apparent complex
      formation constant K') was calculated using several methods: The Langmuir and
      Scatchard linear fits for one and two ligands, the Lorenzo non-linear fit for one
      ligand and Langmuir non-linear fit for two ligands. The capability of the
      different methods to achieve reliable results have been discussed and Langmuir
      linear fit as well as Lorenzo non-linear fit are the most suitable. Cu presented
      the highest ligand concentrations, followed by Zn and Pb, while mean log K'
      values fell in the range 5-9 (+/- 0.6) for all metals and samples. The adjustment
      of the data treatment methods used to calculate the speciation parameters was
      found to vary depending on the extent of complexation and on whether one or two
      ligands needed to be considered.

PMID- 21872035
TI  - Chemical analysis of sulfur species in geothermal waters.
AB  - Analytical methods have been developed to determine sulfur species concentrations
      in natural geothermal waters using Reagent-FreeTM Ion Chromatography (RFTM-IC),
      titrations and spectrophotometry. The sulfur species include SO(4)(2-),
      S(2)O(3)(2-), and ?S(2-) with additional determination of SO(3)(2-) and
      S(x)O(6)(2-) that remains somewhat semiquantitative. The observed workable limits
      of detections were <= 0.5 MUM depending on sample matrix and the analytical
      detection limits were 0.1 MUM. Due to changes in sulfur species concentrations
      upon storage, on-site analyses of natural water samples were preferred.
      Alternatively, the samples may be stabilized on resin for later elution and
      analysis in the laboratory. The analytical method further allowed simultaneous
      determination of other anions including F(-), Cl(-), dissolved inorganic carbon
      (DIC) and NO(3)(-) without sample preservation or stabilization. The power of the
      newly developed methods relies in routine analysis of sulfur speciation of
      importance in natural waters using techniques and facilities available in most
      laboratories doing water sample analysis. The new methods were successfully
      applied for the determination of sulfur species concentrations in samples of
      natural and synthetic waters.

PMID- 21872036
TI  - A novel flow injection chemiluminescence determination of Cr(VI) with
      Dichlorotris(1,10-phenanthroline)ruthenium(II).
AB  - A selective novel reverse flow injection system with chemiluminescence detection
      (rFI-CL) for the determination of Cr(VI) in presence of Cr(III) with Dichlorotris
      (1,10-phenanthroline)ruthenium(II), (Ru(phen)(3)Cl(2)), is described in this
      work. This new method is based on the oxidation capacity of Cr(VI) in H(2)SO(4)
      media. First, the Ruthenium(II) complex is oxidized to Ruthenium(III) complex by
      Cr(VI) and afterwards it is reduced to the excited state of the Ruthenium(II)
      complex by a sodium oxalate solution, emitting light inside the detector. The
      intensity of chemiluminescence (CL) is proportional to the concentration of
      Cr(VI) and, under optimum conditions, it can be determined over the range of 3
      300 MUg L(-1) with a detection limit of 0.9 MUg L(-1). The RSD was 8.4% and 1.5%
      at 5 and 50 MUg L(-1), respectively. For the rFI-CL method various analytical
      parameters were optimized: flow rate (1 mL min(-1)), H(2)SO(4) carrier
      concentration (20% w/V), Ru(phen)(3)Cl(2) concentration (5mM) and sodium oxalate
      concentration (0.1M). The effect of Cr(III), Fe(III), Al(III), Cd(II), Zn(II),
      Hg(II), Pb(II), Ca(II) and Mg(II), was studied. The method is highly sensitive
      and selective, allowing a fast, on-line determination of Cr(VI) in the presence
      of Cr(III). Finally, the method was tested in four different water samples (tap,
      reservoir, well and mineral), with good recovery percentage.

PMID- 21872037
TI  - Isotopic finger-printing of active pharmaceutical ingredients by 13C NMR and
      polarization transfer techniques as a tool to fight against counterfeiting.
AB  - The robustness of adiabatic polarization transfer methods has been evaluated for
      determining the carbon isotopic finger-printing of active pharmaceutical
      ingredients. The short time stabilities of the adiabatic DEPT and INEPT sequences
      are very close to that observed with the one pulse sequence, but the DEPT long
      time stability is not sufficient for isotopic measurements at natural abundance
      or low enrichment. Using the INEPT sequence for (13)C isotopic measurements
      induces a dramatic reduction in the experimental time without deterioration in
      short time or long time stability. It appears, therefore, to be a method of
      choice for obtaining the isotopic finger-print of different ibuprofen samples in
      a minimum time. The results obtained on 13 commercial ibuprofen samples from
      different origins show that this strategy can be used effectively to determine
      (13)C distribution within a given molecule and to compare accurately differences
      in the isotopic distribution between different samples of the given molecule. The
      present methodology is proposed as a suitable tool to fight against
      counterfeiting.

PMID- 21872038
TI  - Differentiation of organic and non-organic ewe's cheeses using main mineral
      composition or near infrared spectroscopy coupled to chemometric tools: a
      comparative study.
AB  - Two independent methodologies were investigated to achieve the differentiation of
      ewes' cheeses from different systems of production (organic and non-organic).
      Eighty cheeses (40 organic and 40 non-organic) from two systems of production,
      two different breeds of ewe, different sizes, seasons (summer and winter) and
      ripening times up to 9 months were elaborated. Their mineral composition or the
      information provided by their spectra in the near infrared zone (NIR) coupled to
      chemometric tools were used in order to differentiate between organic and non
      organic cheeses. Main mineral composition (Ca, K, Mg, Na and P) of cheeses and
      stepwise lineal discriminant analysis were used to develop a discriminant model.
      The results from canonical standardised coefficients indicated that the most
      important mineral was Mg (1.725) followed by P (0.764) and K (0.742). The
      percentage of correctly classified samples was 88% in internal validation and 90%
      in external validation, selecting Mg, K and P as variables.Spectral information
      in the NIR zone was used coupled to a discriminant analysis based on a regression
      by partial least squares in order to obtain a model which allowed a rate of
      samples correctly classified of 97% in internal validation and 85% in external
      validation.

PMID- 21872039
TI  - Identification of phase I metabolites of cardiovascular and anti-ulcer drugs in
      surface water samples with liquid-chromatography-mass spectrometry methods.
AB  - In our study we have identified phase I metabolites of cardiovascular and anti
      ulcer agents with the application of predictive multiple reaction monitoring
      (pMRM) methods with liquid-chromatography-triple-quadrupole mass spectrometry (LC
      QQQ-MS) in surface water samples. Targeted accurate mass spectrometry
      measurements were also carried out for confirmation with liquid-chromatography
      time-of-flight mass spectrometry (LC-TOF-MS). pMRM followed by a targeted
      accurate mass spectrometry measurement can provide a sound basis for the
      selection of metabolites to be included in analytical methods for the
      investigation of environmental load of pharmaceuticals. Using LC-QQQ-MS twenty
      one metabolites could be identified with two independent transitions at the same
      retention time and six of them could also be confirmed with LC-TOF-MS.

PMID- 21872040
TI  - Electrochemical genosensors for the detection of Bonamia parasite. Selection of
      single strand-DNA (ssDNA) probes by simulation of the secondary structure
      folding.
AB  - A post-PCR nucleic acid work by comparing experimental data, from electrochemical
      genosensors, and bioinformatics data, derived from the simulation of the
      secondary structure folding and prediction of hybridisation reaction, was carried
      out in order to rationalize the selection of ssDNA probes for the detection of
      two Bonamia species, B. exitiosa and B. ostreae, parasites of Ostrea edulis. Six
      ssDNA probes (from 11 to 25 bases in length, 2 thiolated and 4 biotinylated) were
      selected within different regions of B. ostreae and B. exitiosa PCR amplicons
      (300 and 304 bases, respectively) with the aim to discriminate between these
      parasite species. ssDNA amplicons and probes were analyzed separately using the
      "Mfold Web Server" simulating the secondary structure folding behaviour. The
      hybridisation of amplicon-probe was predicted by means of "Dinamelt Web Server".
      The results were evaluated considering the number of hydrogen bonds broken and
      formed in the simulated folding and hybridisation process, variance in gaps for
      each sequence and number of available bases. In the experimental part, thermally
      denatured PCR products were captured at the sensor interface via sandwich
      hybridisation with surface-tethered probes (thiolated probes) and biotinylated
      signalling probes. A convergence between analytical signals and simulated results
      was observed, indicating the possibility to use bioinformatic data for ssDNA
      probes selection to be incorporated in genosensors.

PMID- 21872041
TI  - Dual asymmetric-flow microdialysis for in vivo monitoring of brain
      neurochemicals.
AB  - Microdialysis is an extensively used technique for both in vivo and in vitro
      experiments, applicable to animal and human studies. In neurosciences, the in
      vivo microdialysis is usually performed to follow changes in the extracellular
      levels of substances and to monitor neurotransmitters release in the brain of
      freely moving animals. Catecholamines, such as dopamine and their related
      compounds, are involved in the neurochemistry and in the physiology of mental
      diseases and neurological disorders. It is generally supposed that the brain's
      energy requirement is supplied by glucose oxidation. More recently, lactate was
      proposed to be the metabolic substrate used by neurons during synaptic activity.
      In our study, an innovative microdialysis approach for simultaneous monitoring of
      catecholamines, indolamines, glutamate and energy substrates in the striatum of
      freely moving rats, using an asymmetric perfusion flow rate on microdialysis
      probe, is described. As a result of this asymmetric perfusion, two samples are
      available from the same brain region, having the same analytes composition but
      different concentrations. The asymmetric flow perfusion could be a useful tool in
      neurosciences studies related to brain's energy requirement, such as toxin
      induced models of Parkinson's disease.

PMID- 21872042
TI  - Arsenic determination by ICP-QMS with octopole collision/reaction cell. Overcome
      of matrix effects under vented and pressurized cell conditions.
AB  - The determination of arsenic by inductively coupled plasma mass spectrometry (ICP
      MS) in natural waters with high sodium and chloride content has been
      investigated. The instrument used is equipped with an octopole collision/reaction
      cell to overcome spectroscopic interferences. Thus, the optimization of
      collision/reaction gas flow rates is required when using a pressurized cell. A
      mixture of 2.9 mL min(-1) of H(2) and 0.5 mL min(-1) of He has been found to be
      suitable for the removal of (40)Ar(35)Cl(+) interference. The effect of the
      introduction of small amounts of alcohol has also been studied in this work under
      both vented and pressurized cell conditions. It has been observed that the
      presence of 4% (v/v) of ethanol or methanol results in an increase in arsenic
      sensitivity. Moreover, under vented cell conditions the addition of alcohol also
      decreases the formation of polyatomic interference. However, this decrease is not
      observed under pressurized cell conditions. Different elements have been studied
      as possible internal standards for arsenic determination in presence of high
      amounts of sodium. Good results have been obtained for rhodium and yttrium under
      both vented and pressurized cell conditions. Although the presence of alcohol in
      the sample matrix also affects their behaviour, rhodium and yttrium are still the
      most suitable elements to correct for these matrix effects. Different
      experimental conditions have been compared for arsenic determination in spiked,
      certified and natural waters with high sodium and chloride content. The best
      results have been obtained under pressurized cell conditions, in the presence of
      ethanol and using rhodium as internal standard.

PMID- 21872043
TI  - Determination of diclofenac from paediatric urine samples by stir bar sorptive
      extraction (SBSE)-HPLC-UV technique.
AB  - A novel stir bar sorptive extraction (SBSE) method coupled with high performance
      liquid chromatography (HPLC) and UV detection for the extraction of diclofenac
      (DIC) from paediatric urine samples has been developed and validated. Selectivity
      and sensitivity being the prime objectives of the bioanalytical method for
      clinical samples, an optimised SBSE protocol was developed that selectively
      extracted DIC from various concurrently administered drugs. The validated assay
      was found to be linear (r=0.9999) over a concentration range of 100-2000 ng mL(
      1). SBSE showed consistent recoveries (~ 70%) of DIC across the validated
      linearity range. Overall, the method exhibited excellent accuracy and precision
      across all QC concentrations, tested over three days. Calculated LOD and LOQ were
      found to be 12.03 ng mL(-1) and 36.37 ng mL(-1), respectively, however, for the
      experimental purposes, 100 ng mL(-1) was considered as the validated LOQ
      (accuracy and precision at this LQC was <20%). Further, studies on various
      attributes of the stir bar/SBSE, showed no significant inter- and intra-stir bar
      variability for DIC extraction. There was no carryover effect with re-use of
      conditioned stir bars and for the first time, a systematic investigation on the
      effect of ageing of stir bars on their extraction efficiency was carried out.
      Results showed that, for the present study, stir bars which were used 150 times
      were still functional based on in-house acceptance criteria and extraction
      efficiency. The validated method was successfully applied to the analysis of DIC
      in paediatric clinical trial samples.

PMID- 21872044
TI  - Microanalytical method development for Fe, Cu and Zn determination in colorectal
      cancer cells.
AB  - Microanalytical methods suitable for the determination of Fe, Cu in HT-29 (human
      colon adenocarcinoma) cells treated with different iron compounds (Fe(II)
      sulfate, Fe(III) chloride, Fe(III) citrate and Fe(III) transferrin) and cultured
      in medium supplemented or not with 10% (v/v) fetal calf serum (FCS) by total
      reflection X-ray fluorescence spectrometry (TXRF) and simultaneous graphite
      furnace atomic absorption spectrometry (GF-AAS) were developed. The developed
      TXRF method was also suitable for Zn determination in the samples. The main
      advantage of the proposed methods is the execution of all sample preparation
      steps following incubation and prior to the elemental analysis in the same
      Eppendorf tubes. Sample preparation was performed at microscale (115 MUL sample
      volume) with 65% nitric acid and 30% hydrogen peroxide. According to scanning
      electron microscopic measurements, the organic matrix of the cell samples could
      be eliminated to the extent that accurate results were obtained for Cu and Fe by
      analyzing the same samples by TXRF and GF-AAS. Concerning the iron uptake, HT-29
      cells incubated in FCS-free medium contained Fe in cca. 5-50 times higher amounts
      compared to cells cultured in FCS supplemented medium. Pronounced differences in
      the iron uptake compared to the iron supply (inorganic vs. organic chelated as
      well as iron(II) vs. iron(III)) were observed in the case of cell lines incubated
      in FCS-free medium.

PMID- 21872045
TI  - CALUX measurements: statistical inferences for the dose-response curve.
AB  - Chemical Activated LUciferase gene eXpression [CALUX] is a reporter gene
      mammalian cell bioassay used for detection and semi-quantitative analyses of
      dioxin-like compounds. CALUX dose-response curves for 2,3,7,8-tetrachlorodibenzo
      p-dioxin [TCDD] are typically smooth and sigmoidal when the dose is portrayed on
      a logarithmic scale. Non-linear regression models are used to calibrate the CALUX
      response versus TCDD standards and to convert the sample response into
      Bioanalytical EQuivalents (BEQs). Several complications may arise in terms of
      statistical inference, specifically and most important is the uncertainty
      assessment of the predicted BEQ. This paper presents the use of linear
      calibration functions based on Box-Cox transformations to overcome the issue of
      uncertainty assessment. Main issues being addressed are (i) confidence and
      prediction intervals for the CALUX response, (ii) confidence and prediction
      intervals for the predicted BEQ-value, and (iii) detection/estimation
      capabilities for the sigmoid and linearized models. Statistical comparisons
      between different calculation methods involving inverse prediction, effective
      concentration ratios (ECR(20-50-80)) and slope ratio were achieved with example
      datasets in order to provide guidance for optimizing BEQ determinations and
      expand assay performance with the recombinant mouse hepatoma CALUX cell line
      H1L6.1c3.

PMID- 21872046
TI  - Selective preconcentration of thallium species as chloro and iodo complexes on
      Chromosorb 105 resin prior to electrothermal atomic absorption spectrometry.
AB  - A selective preconcentration method was described for the determination of
      inorganic thallium species by electrothermal atomic absorption spectrometry
      (ETAAS). Thallium(III) and thallium(I) as chloro and iodo complexes were
      selectively retained by a column containing 0.5 g of Chromosorb 105 resin and
      quantitatively eluted by 10 mL of pure acetone. The calibration graph was linear
      with a correlation coefficient of 0.997 at levels near the detection limit and up
      to at least 0.8 MUg L(-1). The detection limits for the determination of total
      thallium and thallium(III) employing the proposed method by ETAAS were estimated
      as three values of the standard deviations, 0.050 MUg L(-1) and 0.034 MUg L(-1),
      respectively. Verification of the accuracy was carried out by the analysis of
      standard reference materials (GBW 07402 soil, NIST 2710 Montana soil, GBW 07309
      and GBW 07310 stream sediments). The relative errors were found to be in the
      range of -7.7% to +4.8%. The relative standard deviations were generally found to
      be below 10%. The effect of potential interfering ions on the determination was
      studied. The proposed method was successfully applied to the determination of
      total thallium in five different brand cements, soils around two cement plants
      and metallic zinc samples. The speciation of thallium(I) and thallium(III) was
      applied to synthetic solutions.

PMID- 21872047
TI  - One step electrochemically deposited nanocomposite film of chitosan-carbon
      nanotubes-gold nanoparticles for carcinoembryonic antigen immunosensor
      application.
AB  - A simple and controllable one-step electrodeposition method for the preparation
      of a chitosan-carbon nanotubes-gold nanoparticles (CS-CNTs-GNPs) nanocomposite
      film was used to fabricate an immunosensor for detection of carcinoembryonic
      antigen (CEA). The porous three-dimensional CS-CNTs-GNPs nanocomposite film,
      which offered a large specific surface area for immobilization of antibodies,
      exhibited improved conductivity, high stability and good biocompatibility. The
      morphology of the formed nanocomposite film was investigated by scanning electron
      microscopy (SEM), and the electrochemical behaviors of the immunosensor were
      characterized by electrochemical impedance spectroscopy (EIS) and cyclic
      voltammetry (CV). Under the optimal conditions, the proposed immunosensor could
      detect CEA in two linear ranges from 0.1 to 2.0 ng mL(-1) and from 2.0 to 200.0
      ng mL(-1), with a detection limit of 0.04 ng mL(-1). The immunosensor based on CS
      CNTs-GNPs nanocomposite film as the antibody immobilization matrix could exhibit
      good sensitivity, stability, and reproducibility for the determination of CEA.

PMID- 21872048
TI  - Gold nanoparticles solid contact for ion-selective electrodes of highly stable
      potential readings.
AB  - Internal solution free ion-selective electrodes were prepared applying for the
      first time gold nanoparticles as a solid contact layer. The presence of a layer
      of gold nanoparticles stabilized with aliphatic thiols at the back side of the
      membrane resulted in highly stable potentiometric responses of the sensors, good
      selectivities and close to Nernstian slopes. Electrochemical studies have
      confirmed that the applied material is effectively working as capacitive solid
      contact, yielding high stability sensors.

PMID- 21872049
TI  - Dispersive liquid-liquid microextraction followed by gas chromatography-mass
      spectrometry for the determination of nitro musks in surface water and wastewater
      samples.
AB  - A new, simple, fast and high sensitive analytical method based on dispersive
      liquid-liquid microextraction (DLLME) followed by gas chromatography-mass
      spectrometry (GC-MS) for the simultaneous determination of nitro musks in surface
      water and wastewater samples is presented. Different parameters, such as the
      nature and volume of both the extraction and disperser solvents and the ionic
      strength and pH of the aqueous donor phase, were optimized. Under the selected
      conditions (injection of a mixture of 1 mL of acetone as disperser solvent and 50
      MUL of chloroform as extraction solvent, no salt addition and no pH adjustment)
      the figures of merit of the proposed DLLME-GC-MS method were evaluated. High
      enrichment factors, ranging between 230 and 314 depending on the target analyte,
      were achieved, which redound to limits of detection in the ng L(-1) range (i.e.,
      4-33 ng L(-1)). The relative standard deviation (RSD) was below 5% for all the
      target analytes. Finally, the recoveries obtained for different water samples of
      diverse origin (sea, river, irrigation channel and water treatment plant) ranged
      between 87 and 116%, thus showing no matrix effects.

PMID- 21872050
TI  - Synthesis, characterization and application of a two-fold 13C-labeled calibration
      standard for the analysis of arsenobetaine using HPLC-ESI-MS/MS without high
      resolution mass spectrometry.
AB  - A procedure has been developed for the determination of arsenobetaine in fish
      matrix by HPLC-ESI-MS/MS. Hereby (trimethylarsonium)-1,2-(13)C-acetate
      (arsenobetaine) is used as internal calibration standard. Arsenobetaine was
      determined in a fish material (Sea Bass) with an expanded uncertainty of 3.8%.

PMID- 21872051
TI  - Fast and simple method for determination of fatty acid methyl esters (FAME) in
      biodiesel blends using X-ray spectrometry.
AB  - The determination of fatty acid methyl esters (FAME) in diesel fuel blends is an
      important aspect of production and blending process as well as quality control of
      distribution operations. In this study, energy-dispersive X-ray fluorescence
      spectrometer (EDXRF) is used for the first time for determination of FAME in
      biodiesel blends. The principle of the method is based on intensity difference of
      X-ray radiation scattered from hydrocarbons and from FAME. The experiment shows
      that coherent and incoherent radiation, commonly applied for evaluation of the
      average atomic number of the sample with light matrix, cannot be applied for FAME
      determination. However, the application of scattered continuous radiation gives
      excellent correlation between FAME concentration and intensity of scattered
      radiation. The best results are obtained if continuum is collected in the range
      of energy between 10.5 and 15.0 keV for rhodium X-ray tube, operated at 35 kV.
      Linear relationship between the FAME concentration and the inverse of scattered
      continuous radiation is obtained with the correlation coefficients of 0.999.
      Standard deviation of measurement is ca. 0.46% (v/v) of FAME and detection limit
      is 1.2% (v/v) for 600 s counting time and 50% dead-time loss using Si-PIN
      detector. The investigation shows that crucial issue in determination of FAME in
      biodiesel blends using EDXRF spectrometer is the precision of measurements
      resulting from the counting statistics. Therefore, much better results (0.20%
      (v/v) standard deviation and 0.52% (v/v) detection limit) can be expected if
      higher intensity of primary radiation is applied and X-ray spectrum is collected
      by silicon drift detector of high input count rate. For concentration of FAME
      from 10 to 100% (v/v), the differences between reference method (Fourier
      transform infrared spectrometry) and the proposed method usually do not exceed 1%
      (v/v) of FAME. The proposed method is fast, simple and enables FAME determination
      in wide range of concentration up to 100% of FAME without any sample treatment.

PMID- 21872052
TI  - Sensitive detection of endocrine disrupters using ionic liquid--single walled
      carbon nanotubes modified screen-printed based biosensors.
AB  - Simple and low cost biosensor based on screen-printed electrode for sensitive
      detection of some alkylphenols was developed, by entrapment of HRP in a
      nanocomposite gel based on single-walled carbon nanotubes (SWCNTs) and 1-butyl-3
      methylimidazolium hexafluorophosphate ([BMIM][PF(6)]) ionic liquid. Raman and
      FTIR spectroscopy, CV and EIS studies demonstrate the interaction between SWCNTs
      and ionic liquid. The nanocomposite gel, SWCNT-[BMIM][PF(6)] provides to the
      modified sensor a considerable enhanced electrocatalytic activity toward hydrogen
      peroxide reduction. The HRP based biosensor exhibits high sensitivity and good
      stability, allowing a detection of the alkylphenols at an applied potential of 
      0.2V vs. Ag/AgCl, in linear range from 5.5 to 97.7 MUM for 4-t-octylphenol and
      respectively, between 5.5 and 140 MUM for 4-n-nonylphenol, with a response time
      of about 5s. The detection limit was 1.1 MUM for 4-t-octylphenol, and
      respectively 0.4 MUM for 4-n-nonylphenol (S/N=3).

PMID- 21872053
TI  - Composition of structural carbohydrates in biomass: precision of a liquid
      chromatography method using a neutral detergent extraction and a charged aerosol
      detector.
AB  - We adapted and optimized a method to quantify the cellulose, hemicellulose,
      xylan, arabinan, mannan, galactan contents in lignocellulosic biomass. This
      method is based on a neutral detergent extraction (NDE) of the interfering
      biomass components, followed by a sulfuric acid hydrolysis (SAH) of the
      structural polysaccharides, and a liquid chromatography with charged aerosol
      detection (LC-CAD) to analyze the released monosaccharides. The first step of
      this NDE-SAH-LC-CAD method aims at removing all compounds that interfere with the
      subsequent sulphuric acid hydrolysis or with the subsequent chromatographic
      quantification of the cellulosic and hemicellulosic monosaccharides. This step
      includes starch hydrolysis with an analytical thermostable alpha-amylase followed
      by an extraction of soluble compounds by a Van Soest neutral detergent solution
      (NDE). The aim of this paper was to assess the precision of this method when
      choosing fiber sorghum (Sorghum bicolor (L.) Moench), tall fescue (Festuca
      arundinacea Schreb.) and fiber hemp (Cannabis sativa L.) as representative
      lignocellulosic biomass. The cellulose content of fiber sorghum, tall fescue and
      fiber hemp determined by the NDE-SAH-LC-CAD method were 28.7 +/- 1.0, 29.7 +/-
      1.0 and 43.6 +/- 1.2g/100g dry matter, respectively, and their hemicellulose
      content were 18.6 +/- 0.5, 16.5 +/- 0.5 and 14.5 +/- 0.2g/100g dry matter,
      respectively. Cellulose, mannan and galactan contents were higher in fiber hemp
      (dicotyledon) as compared to tall fescue and fiber sorghum (monocotyledons). The
      xylan, arabinan and total hemicellulose contents were higher in tall fescue and
      fiber sorghum as compared to fiber hemp. The precision of the NDE-SAH-LC-CAD
      method was better for polysaccharide concentration levels above 1g/100g dry
      matter. Galactan analysis offered a lower precision, due to a lower CAD response
      intensity to galactose as compared to the other monosaccharides. The dispersions
      of the results (expanded uncertainty) of the NDE-SAH-LC-CAD method were smaller
      as compared to the Van Soest (VS) method. In addition, the NDE-SAH-LC-CAD method
      was able to provide additional information on the composition of the
      hemicellulose (xylan, arabinan, mannan and galactan content) that is not provided
      by the Van Soest method. The NDE-SAH-LC-CAD method offers also the advantage of a
      better specificity for hemicellulose and cellulose, as compared to the NREL and
      Uppsala methods.

PMID- 21872054
TI  - Evaluation of settled floor dust for the presence of microbial metabolites and
      volatile anthropogenic chemicals in indoor environments by LC-MS/MS and GC-MS
      methods.
AB  - This study reports on detection of a large number of biological and anthropogenic
      pollutants using LC-MS/MS and GC-MS technologies in settled floor dust (SFD). The
      latter technique was applied to obtain a general picture on the presence of
      microbial as well as non-microbial volatile organic compounds, whereas the
      targeted LC-MS/MS analysis focused on identification of species specific
      secondary metabolites. In the absence of moisture monitoring data the relevance
      of finding of stachybotrylactam and other metabolites of tertiary colonizers are
      confined only to accidental direct exposure to SFD. To the best of our knowledge
      30 of the 71 identified volatile organic compounds (VOCs) are newly reported in
      SFD matrix. Coordinated application of "AMDIS and Spectconnect" was found
      beneficial for the evaluation and identification of prime volatile pollutants in
      complex environmental samples. Principal component analysis (PCA) of peak areas
      of 18 microbial volatile organic compounds (MVOCs) resulted in identification of
      nonanal as potential MVOC marker. Two more volatiles toluene and 1-tetradecanol
      though had discriminative influence, are not regarded as MVOC markers,
      considering their probable alternate origin from paints and cosmetics,
      respectively.

PMID- 21872055
TI  - The CALUX bio-assay: analytical comparison between mouse hepatoma cell lines with
      a low (H1L6.1c3) and high (H1L7.5c1) number of dioxin response elements.
AB  - Dioxins, furans and polychlorinated biphenyls are contaminants of high concern
      and as such, sensitive tools are needed to detect these persistent organic
      compounds in a variety of matrices. Due to the large amount of samples that need
      to be investigated for example for food and feed control, the CALUX bioassay
      (H1L6.1 clone) was developed allowing rapid and cost-efficient analysis of
      biological and environmental samples. Recently, a new and more sensitive clone
      (H1L7.5) was constructed as the third generation CALUX bioassay. This new cell
      line was subject of an amplification of dioxin response elements (DREs), allowing
      lower concentrations of target compound to be analyzed. A comparison is made
      between the previous, well-defined H1L6.1c3 cell line and the new H1L7.5c1 cell
      line: it appears that the bioassay making use of the higher number of DREs is
      more stable and robust, shows better repeatability and reproducibility and is; on
      average, 3 times more sensitive.

PMID- 21872056
TI  - Application of flow-injection potentiometric system for determination of total
      concentration of aliphatic carboxylic acids.
AB  - In this work, flow-injection system with potentiometric detection was tested for
      determination of total carboxylic acid concentration. Detection part of the
      examined system consists of ion-selective electrodes (ISEs) with polymer
      membranes of different compositions. First electrode is based on Zr(IV)
      tetraphenylporphyrin as ionophore selective towards carboxylic acid anions, the
      membrane of second one contains only liphophilic anion exchanger -
      tridodecylmethylammonium chloride. Final response of the system is a result of
      combination of EMF signals from both electrodes. Combination of two detectors
      enables significant decrease of differences between potentiometric signals
      induced by mixtures of studied anions of various concentrations as compared to
      results obtained only with metalloporphyrin-based ISE. The use of anion-exchanger
      based detector allows for elimination of the influence of aliphatic carboxylic
      acids lipophilicity. Proposed potentiometric flow-injection system was employed
      for determination of short-chain aliphatic carboxylic acids (so-called VFA -
      volatile fatty acids) in samples originating from an anaerobic digester. Results
      obtained for these relatively complicated samples are in good agreement with
      results obtained with the use of reference colorimetric method. Linear response
      towards carboxylic acids was observed in the concentration range of 10(-4) to 10(
      2)mold m(-3), with the slopes in the range of -110 to -150 mV dec(-1) (for
      acetate(-) and butyrate(-), respectively). System enables for determination of
      about 6 samples per hour. Life time of ISEs average about 2 months.

PMID- 21872057
TI  - Simultaneous quantification of bisphenol A and its glucuronide metabolite (BPA-G)
      in plasma and urine: applicability to toxicokinetic investigations.
AB  - Bisphenol A (BPA) is a widely used plasticizer that can contaminate food and the
      wider environment and lead to human exposure. In humans, it is mainly metabolized
      to bisphenol A-glucuronide (BPA-G) and eliminated in the urine. As BPA causes
      adverse physiological effects at low doses, it is necessary to document the
      toxicokinetics of both molecules for risk assessment. Because BPA-G is not
      available as an analytical standard, it is usually quantified after the assay of
      BPA, following an enzymatic hydrolysis with beta-glucuronidase. With this
      approach, two separate assays are required for BPA and BPA-G quantification,
      which can lead to critical pitfalls in terms of accuracy and analysis time. To
      overcome this problem, we have developed a new method for the isolation and
      purification of BPA-G from urine by flash chromatography. Large amounts of BPA-G
      (1g) were isolated and characterized by mass spectrometry and NMR. This BPA-G is
      suitable for an use as analytical standard and enabled us to develop a novel
      method for the simultaneous quantification of BPA and BPA-G in biological
      matrices by UPLC/MS/MS. It has also been used for in vivo toxicokinetic studies
      in sheep. The method of quantification was validated according FDA guidelines and
      used to monitor the time course of plasma and urine concentrations of BPA or BPA
      G following their administration. The simultaneous quantification of BPA and BPA
      G was compared to the commonly used method for urine and plasma samples. For
      plasma samples, the results obtained with the direct assay of BPA-G were similar
      to those obtained by quantification after enzymatic hydrolysis. With urine
      samples, the simultaneous quantification appeared to be more suitable than the
      hydrolysis method for the BPA-G determination.

PMID- 21872058
TI  - Multivariate analysis of the polyphenol composition of Tempranillo and Graciano
      red wines.
AB  - Vitis vinifera L. cv Graciano is often used as a blending partner of Tempranillo
      based wines because it is considered to contribute significantly to the quality.
      The aim of this study is to discriminate between Tempranillo and Graciano
      monovarietal wines, and those made by the incorporation of 20% of Graciano
      variety in two different stages (at the end of malolactic fermentation and mixing
      the two grape varieties in the pre-fermentative maceration stage) of the
      winemaking process of the Tempranillo variety. To achieve this, supervised and
      unsupervised pattern recognition tools were applied to the data obtained in the
      study of the detailed polyphenolic composition, colour and other oenological
      parameters (143 variables). Patterns related to stages in the winemaking and
      ageing process, different wines and vintages can be observed using principal
      component analyses. Furthermore, linear discriminant analysis has been applied in
      order to characterise the wine samples. From the 143 variables, flavan-3-ols have
      exerted a profound influence on wine differentiation.

PMID- 21872059
TI  - Cobalt phthalocyanine as a biomimetic catalyst in the amperometric quantification
      of dipyrone using FIA.
AB  - A biomimetic sensor for the determination of dipyrone was prepared by modifying
      carbon paste with cobalt phthalocyanine (CoPc), and used as an amperometric
      detector in a flow injection analysis (FIA) system. The results of cyclic
      voltammetry experiments suggested that CoPc behaved as a biomimetic catalyst in
      the electrocatalytic oxidation of dipyrone, which involved the transfer of one
      electron. The optimized FIA procedure employed a flow rate of 1.5 mL min(-1), a
      75 MUL sample loop, a 0.1 mol L(-1) phosphate buffer carrier solution at pH 7.0
      and amperometric detection at a potential of 0.3 V vs. Ag/AgCl. Under these
      conditions, the proposed method showed a linear response for dipyrone
      concentrations in the range 5.0 * 10(-6)-6.3 * 10(-3) mol L(-1). Selectivity and
      interference studies were carried out in order to validate the system for use
      with pharmaceutical and environmental samples. In addition to being
      environmentally friendly, the proposed method is a sensitive and selective
      analytical tool for the determination of dipyrone.

PMID- 21872060
TI  - Development and validation of LC-ESI-MS method for sensitive, accurate and rapid
      determination of UC-781 in New Zealand white rabbit plasma.
AB  - The highly potent non-nucleoside reverse transcriptase inhibitor UC-781 is under
      development as a potential microbicide to prevent sexual transmission of human
      immunodeficiency virus type 1 (HIV-1). A sensitive and reproducible liquid
      chromatography-mass spectrometric method has been developed and validated for the
      quantification of the drug in New Zealand white rabbit plasma after liquid-liquid
      extraction procedure. The method was validated over the range of 1-500 ng mL(-1).
      Average recoveries of the extraction method were high and consistent: 72%. The
      method is accurate with average accuracies over three QC (n=30) concentrations
      ranging from 99.9% to 106.1%, and precise (within-day and between-day precision
      measures ranging from 2.2% to 9.9% and 6.50% to 9.0%, respectively). Plasma from
      other three species proved that extraction method did no affect analyte and
      internal standard stability. Due to its critical and consequential use, this
      assay could be readily used for investigational or clinical monitoring of plasma
      concentrations for low concentration as 1 ng mL(-1) without interference.

PMID- 21872061
TI  - Effect of several variables in the polymer toys additive migration to saliva.
AB  - Capacity to migrate of a representative group of polymeric additives, dyes,
      antioxidants, hindered amine light stabilizers (HALS) or antistatics, from
      plastic toys to saliva was analyzed to protect children in their habits of
      sucking and biting. Most of target additives appear no-regulated in toys
      normative but adverse effects on human health of some of them have been
      demonstrated and their presence in others commercial articles normative has been
      included. In order to offer an effective and easy tool to perform these controls,
      migration tests by dynamic and static contact, followed by a preconcentration
      step by liquid-liquid extraction (LLE) and ultra performance liquid
      chromatographic analysis with ultraviolet-visible and evaporative light
      scattering detections (UPLC-UV/Vis-ELSD) have been optimized to evaluate the
      migrated amounts of the additives in saliva simulant. The detection limits of the
      migration methodologies were ranged from 8.68 * 10(-2) to 1.30 * 10(-3)mg
      migrated (L simulant)(-1). Influence of several variables on this mass transport,
      as time, temperature and friction, was also analyzed to achieve the most
      aggressive methodology to protect consumers. Migration of several studied
      additives, whose presence has been demonstrated in several purchased commercial
      toys, has been observed.

PMID- 21872062
TI  - Remobilization of pentavalent antimony and vanadium from a granular iron
      hydroxide material--a comparative study of different leaching systems.
AB  - The remobilization of antimony and vanadium from previously loaded commercial
      granular ferric-hydroxide GEH material (intended for water treatment) was
      examined by using a sequential extraction procedure and three different leaching
      systems to evaluate their physicochemical mobility and potential availability
      under different simulated environmental conditions. A classical batch extraction,
      an extraction cell (EC) and rotating-coiled columns (RCC) were used as extraction
      systems. For each system it could be shown that the content of ion-exchangeable
      antimony and vanadium in previously loaded material is negligible (<1.5%). The
      oxyanions were sorbed strongly and could be predominantly remobilized through
      reducing agents, which means through dissolution of the iron (hydr)oxide matrix.
      The major advantages of dynamic systems in comparison to batchwise fractionation
      technique are the drastically reduced extraction time and the possibility of
      generating information to the leaching kinetics. It is shown that the efficiency
      of the three leaching systems is quite different employing Wenzel's sequential
      fractionation protocol. Only by working with RCC, the iron (hydr)oxide matrix was
      completely dissolved within four steps resulting in the total mobilization of
      antimony and vanadium. EC seems to be less suitable for leaching studies of Sb
      and V sorbed on iron(hydr)oxide. The remobilizable proportion of the several
      fractions was lower in comparison to batch and RCC and seems to be a result of an
      agglomeration of the GEH in the EC device.

PMID- 21872063
TI  - Surface plasmon resonance detection of oligonucleotide sequences of the rpoB
      genes of Mycobacterium tuberculosis.
AB  - Oligonucleotide sequences related to the normal and mutated rpoB genes of
      Mycobacterium tuberculosis are detected using a surface plasmon resonance (SPR)
      biosensor system. A bioselective element was prepared by immobilizing the thiol
      modified oligonucleotides of the selected sequence (the capture probe P2) that
      contains the mutated TCG->TTG codon 531 (evoking drug resistance) of the rpoB
      gene of M. tuberculosis on a gold sensor surface. Specific hybridization between
      immobilized probe P2 and complementary target T2 gave the highest sensor
      response, single-base mismatched oligonucleotide TN (corresponding to the normal
      gene sequence) produced somewhat smaller response and no response was observed at
      injection of noncomplementary oligonucleotide TC. The P2-T2 hybridization
      efficiency is calculated ca. 30% (5 * 10(12) molecules cm(-2)), and the lowest
      detection limit of T2 was 10nM. An extended T2E oligonucleotide sequence
      consisting of T2 sequence and additional 24 nucleotides was shown to cause more
      pronounced sensor response (at least 5 nM T2E was easily detected). Injection
      into the sensor cell of the oligonucleotides complementary to the free additional
      part of T2E after P2-T2E hybridization gave a significant additional SPR
      response, thus showing that the sandwich hybridization format further improves
      the sensor sensitivity and decreases the lowest detection limit. The experimental
      results on surface hybridization between the studied oligonucleotides were in
      good agreement with thermodynamic parameters of the hybridization calculated for
      solution conditions. The described approach could be proposed as a basis for
      creating a biosensor for real-time and label-free diagnostics of drug resistant
      tuberculosis.

PMID- 21872064
TI  - Determination of dicofol in aquatic products using molecularly imprinted solid
      phase extraction coupled with GC-ECD detection.
AB  - The novel molecularly imprinted microsphere (MIM) that could be applied as
      special sorbent was synthesized by aqueous suspension polymerization using 1,1
      bis(4-chlorophenyl)-1,2,2,2-tetrachloroethane (alpha-chloro-DDT) as the dummy
      template. The obtained MIM exhibited good recognition and selectivity to dicofol
      and it was successfully applied as selective sorbent of solid-phase extraction
      for the determination of dicofol from aquatic products. At the optimum conditions
      of the molecularly imprinted solid-phase extraction (MISPE) coupled with GC-ECD,
      good linearity for dicofol was achieved in a range of 0.4-100 ng g(-1)
      (r(2)=0.9995) and the recoveries at three spiked levels were ranged from 85.8% to
      101.2% for aquatic products with the relative standard deviation (RSD) less than
      5.6%. The presented MISPE-GC-ECD method exhibited the advantages of simplicity,
      selectivity and sensitivity, and could be potentially applied to the
      determination of dicofol in complicated aquatic products.

PMID- 21872065
TI  - Layer-by-layer assembled multilayer of graphene/Prussian blue toward simultaneous
      electrochemical and SPR detection of H2O2.
AB  - A new type of chemically converted graphene sheets, cationic polyelectrolyte
      functionalized ionic liquid decorated graphene sheets (PFIL-GS) composite, was
      synthesized and characterized by Ultraviolet-visible (UV-vis) absorption, Fourier
      transform infrared, and Raman spectroscopy. It was found that the presence of
      PFIL enabled the formation of a very stable aqueous dispersion due to the
      electrostatic repulsion between PFIL modified graphene sheets. With respect to
      the excellent dispersibility of this material, we have fabricated a novel PFIL
      GS/Prussian blue (PB) nanocomposite multilayer film via classic layer-by-layer
      (LBL) assembly. The assembly process was confirmed by UV-vis spectroscopy and
      surface plasmon resonance (SPR) spectroscopy, which showed linear responses to
      the numbers of the deposited PFIL-GS/PB bilayers. Moreover, the as-prepared
      composite films were used to detect hydrogen peroxide (H(2)O(2)) by
      electrochemical surface plasmon resonance (EC-SPR) spectroscopy. This real time
      EC-SPR technique can provide simultaneous monitoring of both optical SPR signal
      and electrochemical current responses upon injecting H(2)O(2) into the reaction
      cell. The experimental results revealed that both the electrochemical and SPR
      signal exhibited splendid linear relationship to the concentration of the
      injected H(2)O(2), and the detection limit could be up to 1 MUM.

PMID- 21872066
TI  - Aptamer-quantum dots conjugates-based ultrasensitive competitive electrochemical
      cytosensor for the detection of tumor cell.
AB  - A novel competitive electrochemical cytosensor was reported by using aptamer
      (Apt)-quantum dots (Qdots) conjugates as a platform for tumor cell recognition
      and detection. The complementary DNA (cDNA), aptamer and Qdots could be assembled
      to the gold electrode surface. When the target cells existed, they could compete
      with cDNA to bind with Apt-Qdots conjugates based on the specific recognition of
      aptamer to MUC1 protein overexpressed on the cell surface, which resulted in the
      denaturation of double-stranded DNA structure and the release of the Apt-Qdots
      conjugates from the electrode. Electrochemical stripping measurement was then
      employed to determine the Cd(2+) concentration in Qdots left at the electrode.
      The peak current was inversely proportional to the logarithmic value of cell
      concentration ranging from 1.0 * 10(2) to 1.0*10(6) cells mL(-1) with a detection
      limit of 100 cells mL(-1). Meanwhile, the recognition of aptamer to the target
      cells could be clearly observed through the strong fluorescence from Qdots. This
      is an example of the combination of aptamer and nanoparticles for the application
      of cell analysis, which is essential to cancer diagnosis and therapy.

PMID- 21872067
TI  - An efficient one-pot reaction for selective fluorimetric determination of
      cefpodoxime and its prodrug.
AB  - Cefpodoxime proxetil (CFP), an oral third-generation cephalosporin, is a prodrug
      that is de-esterified in vivo to its active metabolite, cefpodoxime acid (CFA).
      Therefore, this study aimed to develop a facile and efficient one-pot reaction
      for selective and sensitive determination of CFA and its prodrug (CFP). The
      method was based on single-step reaction between CFP or CFA and 1,2
      naphthoquinone-4-sulfonate (NQS) as a selective derivatizing reagent in alkaline
      medium without heating, extraction or reduction steps as usual for NQS
      derivatization reactions. The fluorescence of the formed NQS-derivative was
      monitored directly at emission wavelength of 440 nm after excitation at 330 nm.
      The method can easily be implemented in plating facilities by operators and/or
      incorporated in on-line derivatization reaction. The correlation coefficients of
      0.9991 and 0.9984 were obtained in the concentration ranges of 50-2000 ng mL(-1)
      for CFA and CFP, respectively. The detection limits were 9.17 and 9.48 ng mL(-1)
      for CFA and CFP, respectively. The method was validated in accordance with the
      requirements of ICH guidelines and shown to be suitable for their efficient and
      sensitive determinations. The developed method was successfully applied for
      selective determination of CFP in pure form and in pharmaceutical dosage forms as
      well as CFA in human urine after single dose of CFP without prior need for
      separation. The method is valuable for quality control laboratories for
      monitoring of CFP and its active metabolite CFA.

PMID- 21872068
TI  - Fabrication of a nanostructure-based electrochemical sensor for simultaneous
      determination of N-acetylcysteine and acetaminophen.
AB  - A carbon-paste electrode modified with 2,7-bis(ferrocenyl ethyl)fluoren-9-one
      (2,7-BF) and carbon nanotubes (CNTs) was used for the sensitive and selective
      voltammetric determination of N-acetylcysteine (NAC). The mediated oxidation of
      NAC at the modified electrode was investigated by cyclic voltammetry (CV). Also,
      the values of catalytic rate constant (k), and diffusion coefficient (D) for NAC
      were calculated. Differential pulse voltammetry (DPV) of NAC at the modified
      electrode exhibited two linear dynamic ranges with a detection limit (3sigma) of
      52.0 nmol L(-1). DPV was used for simultaneous determination of NAC and
      acetaminophen (AC) at the modified electrode, and quantitation of NAC and AC in
      some real samples by the standard addition method.

PMID- 21872069
TI  - Enzyme digestion of entrapped single-DNA molecules in nanopores.
AB  - The real-time digestion of entrapped single-DNA molecules by lambda-exonuclease
      in nanoporous alumina membranes was observed using an epifluorescence microscope.
      The alumina membrane provides pL (~ 10(-12)L) containers for confining single-DNA
      molecules without immobilization. When one end of the DNA molecule was inserted
      into a nanopore, it was possible to monitor the digestion process outside, near
      and inside the pore, where the individual DNA molecules exhibited different
      characteristic digestion modes. The digestion rates calculated from the decrease
      in fluorescence intensity showed different values according to the location of
      the individual molecules. Entrapment rather than immobilization allows the DNA
      strand to be fully exposed to the enzyme and the reaction buffer. These results
      confirm that the enzymatic digestion of DNA molecules is affected by their three
      dimensional (3D) environment.

PMID- 21872070
TI  - Detection of lead ions in picomolar concentration range using underpotential
      deposition on silver nanoparticles-deposited glassy carbon electrodes.
AB  - The efficacy of silver-deposited glassy carbon electrode for the determination of
      lead ions at the sub-nanomolar concentration ranges is investigated. The silver
      nanoparticles are electrodeposited on glassy carbon electrode using
      chronoamperometry and the electrode surface is characterized using SEM. Lead ions
      are detected in the region of underpotential deposition. The analysis is
      performed in square wave mode in the stripping voltammetry without the removal of
      oxygen. The detection limit of 10 pM has been obtained with a constant potential
      of -0.7 V during the electrodeposition step for a period of 50s. The interference
      of surfactants in the detection of lead ions is also studied.

PMID- 21872071
TI  - Centrifuge microextraction coupled with sweeping-MEKC to analyze trace steroid
      hormones in urine samples.
AB  - A novel method that combines two concentration techniques, off-line centrifuge
      microextraction (CME) and on-line sweeping, is used to determine trace steroids
      in urine by micellar electrokinetic chromatography (MEKC). The CME-sweeping-MEKC
      is a promising technique, which has a variety of merits such as high sensitivity,
      rapid operation, minimal cost, and high sample throughput capability. Using CME
      sweeping, over a 500-fold increase in sensitivity could be obtained as compared
      with the normal hydrodynamic injection without sample stacking. The linear range
      was 0.05-1 MUg mL(-1) with the square of the correlation coefficients ranging
      from 0.9998 to 0.9999. Detection limits (S/N=3) were 5-15 ng mL(-1) using a
      photodiode array UV detection at a wavelength of 240 nm. The relative standard
      deviations were between 2.8% and 3.5% (n=5, progesterone as the internal
      standard). The diode array UV spectrum used can distinguish the analytes from the
      interference in the complex sample matrix, which is useful in biological and
      clinical sample analysis.

PMID- 21872072
TI  - Carbon nanospheres enhanced electrochemiluminescence of CdS quantum dots for
      biosensing of hypoxanthine.
AB  - This work developed a novel method to greatly enhance the
      electrochemiluminescence (ECL) of CdS quantum dots (QDs). The ECL amplification
      was achieved by the assembly of QDs on poly (diallyldimethylammonium chloride)
      functionalized carbon nanospheres (PFCNSs), and successfully employed for
      sensitive ECL biosensing of oxidase substrates. The carbon nanospheres were
      prepared by a "green" method, and the high loading of QDs on carbon nanospheres
      led to a 4-times increased ECL intensity with dissolved O(2) as the coreactant.
      Using xanthine oxidase (XOD) as a model, an ECL biosensor was fabricated by
      immobilizing the enzyme on the mixing membrane of PFCNSs and QDs. The ECL
      biosensor showed a fast response to hypoxanthine with a linear concentration
      range from 2.5 * 10(-8) to 1.4 * 10(-5)M. The limit of detection was 5 nM at a
      signal-to-noise ratio of 3. The assay results of hypoxanthine in fish samples
      were in a good agreement with the reference values by amperometric technique.
      This facile approach to prepare the PFCNSs/QDs system for ECL biosensing could be
      of promising application in bioanalysis and electronic device.

PMID- 21872073
TI  - Screening analysis to detect adulteration in diesel/biodiesel blends using near
      infrared spectrometry and multivariate classification.
AB  - This paper proposes an analytical method to detect adulteration of
      diesel/biodiesel blends based on near infrared (NIR) spectrometry and supervised
      pattern recognition methods. For this purpose, partial least squares discriminant
      analysis (PLS-DA) and linear discriminant analysis (LDA) coupled with the
      successive projections algorithm (SPA) have been employed to build screening
      models using three different optical paths and the following spectra ranges:
      1.0mm (8814-3799 cm(-1)), 10mm (11,329-5944 cm(-1) and 5531-4490 cm(-1)) and 20mm
      (11,688-5952 cm(-1) and 5381-4679 cm(-1)). The method is validated in a case
      study involving the classification of 140 diesel/biodiesel blend samples, which
      were divided into four different classes, namely: diesel free of biodiesel and
      raw vegetal oil (D), blends containing diesel, biodiesel and raw oils (OBD),
      blends of diesel and raw oils (OD), and blends containing a fraction of 5% (v/v)
      of biodiesel in diesel (B5). LDA-SPA models were found to be the best method to
      classify the spectral data obtained with optical paths of 1.0 and 20mm.
      Otherwise, PLS-DA shows the best results for classification of 10mm cell data,
      which achieved a correct prediction rate of 100% in the test set.

PMID- 21872074
TI  - Synthesis of polyethylene glycol (PEG) assisted tungsten oxide (WO3)
      nanoparticles for L-dopa bio-sensing applications.
AB  - Nanocrystalline tungsten oxides (WO(3-delta)) are currently receiving a lot of
      attention because of their interesting electrical, magnetic, optical and
      mechanical properties. In this report, we present the synthesis of PEG assisted
      tungsten oxide (WO(3)) nanoparticles by simple household microwave irradiation
      (2.45 GHz) method. The samples were characterized using powder X-ray diffraction
      (XRD), thermal analysis (TG/DTA), transmission electron microscopy (TEM), UV
      visible diffusion reflectance spectroscopy (UV-VIS-DRS), cyclic voltammetry and
      electrochemical impedance spectroscopy. Powder XRD results revealed that both the
      samples prepared with and without surfactant crystallize in the orthorhombic
      structure corresponding to WO(3) . H(2)O phase. Subsequent annealing under
      identical conditions (600 degrees C/air/6h) led to significantly different
      products i.e. monoclinic W(17)O(47) from surfactant free sample and orthorhombic
      WO(3) from PEG assisted sample. Blue emission was observed through UV-VIS-DRS
      with blue shift and the band gap energy was estimated as 2.7 and 3.28 eV for PEG
      assisted as prepared (WO(3) . H(2)O) and annealed samples (WO(3)) respectively.
      Electrochemical measurements have been performed on all the samples deposited on
      the surface of glassy carbon (GC) electrode which showed high sensitivity and
      good selectivity for PEG assisted sample (WO(3) . H(2)O) for the direct detection
      of L-dopa.

PMID- 21872075
TI  - Fast liquid chromatography-diode array detection assisted by chemometrics for
      quantification of seven ultraviolet filters in effluent wastewater.
AB  - A fast chromatographic method is presented for simultaneous quantification of
      seven organic ultraviolet (UV) filters (benzophenone-3,4-methylbenzilidene
      camphor, octocrylene, 1-(4-tert-butylphenyl)-3-(4-methyoxyphenyl)1,3
      propanedione), ethylhexyl methoxy cinnamate, ethylhexyl salicylate and
      homosalate) in effluent wastewater samples. The UV filters were pre-concentrated
      by Bond Elut-ENV cartridges and separated on an ODS column (15 cm * 0.46 cm, 5
      MUm) in less than 2.5 min using a non-aqueous mobile phase of methanol
      acetonitrile (50:50, v/v) with flow-rate of 1.5 mL min(-1). Appropriate baseline
      correction through asymmetric least squares was applied to reduce the matrix of
      background signals in three way data. Then, second-order calibration based on
      multivariate curve resolution-alternating least squares (MCR-ALS) was implemented
      on the unfolded three-way data obtained from liquid chromatography with diode
      array detection (LC-DAD) through standard addition calibration method for
      handling co-eluted peaks, systematic and proportional errors. Recoveries ranging
      from 76% to 130% and %RSD values less than 11.2 for all UV filter shows the
      accuracy and precision of the proposed method in wastewater samples. In addition,
      statistical t-test as well as computed elliptical joint confidence region (EJCR)
      confirms the accuracy of the proposed method and indicates the absence of both
      constant and proportional errors in the predicted concentrations. This study
      demonstrates that coupling of the fast HPLC-DAD method with powerful algorithm of
      MCR-ALS can be considered as an efficient method for quantification of UV filters
      in highly contaminated samples of wastewaters where both time and cost per each
      analysis can be reduced significantly.

PMID- 21872076
TI  - Determination of inorganic selenium species in water and garlic samples with on
      line ionic liquid dispersive microextraction and electrothermal atomic absorption
      spectrometry.
AB  - A non-chromatographic separation and preconcentration method for Se species
      determination based on the use of an on-line ionic liquid (IL) dispersive
      microextraction system coupled to electrothermal atomic absorption spectrometry
      (ETAAS) is proposed. Retention and separation of the IL phase was achieved with a
      Florisil((r))-packed microcolumn after dispersive liquid-liquid microextraction
      (DLLME) with tetradecyl(trihexyl)phosphonium chloride IL (CYPHOS((r)) IL 101).
      Selenite [Se(IV)] species was selectively separated by forming Se-ammonium
      pyrrolidine dithiocarbamate (Se-APDC) complex followed by extraction with
      CYPHOS((r)) IL 101. The methodology was highly selective towards Se(IV), while
      selenate [Se(VI)] was reduced and then indirectly determined. Several factors
      influencing the efficiency of the preconcentration technique, such as APDC
      concentration, sample volume, extractant phase volume, type of eluent, elution
      flow rate, etc., have been investigated in detail. The limit of detection (LOD)
      was 15 ng L(-1) and the relative standard deviation (RSD) for 10 replicates at
      0.5 MUg L(-1) Se concentration was 5.1%, calculated with peak heights. The
      calibration graph was linear and a correlation coefficient of 0.9993 was
      achieved. The method was successfully employed for Se speciation studies in
      garlic extracts and water samples.

PMID- 21872077
TI  - Fabrication of a highly sensitive electrochemiluminescence lactate biosensor
      using ZnO nanoparticles decorated multiwalled carbon nanotubes.
AB  - ZnO nanoparticles (nanoZnO) were decorated on multiwalled carbon nanotubes
      (MWCNTs) and then the prepared nano-hybrids, nanoZnO-MWCNTs, were immobilized on
      the surface of a glassy carbon electrode (GCE) to fabricate nanoZnO-MWCNTs
      modified GCE. The prepared electrode, GCE/nanoZnO-MWCNTs, showed excellent
      electrocatalytic activity towards luminol electrochemiluminescence (ECL)
      reaction. The electrode was then further modified with lactate oxidase and Nafion
      to fabricate a highly sensitive ECL lactate biosensor. Two linear dynamic ranges
      of 0.01-10 MUmol L(-1) and 10-200 MUmol L(-1) were obtained for lactate with the
      correlation coefficient better than 0.9996. The detection limit (S/N=3) was 4
      nmol L(-1) lactate. The relative standard deviation for repetitive measurements
      (n=6) of 10 MUmol L(-1) lactate was 1.5%. The fabrication reproducibility for
      five biosensors prepared and used in different days was 7.4%. The proposed ECL
      lactate biosensor was used for determination of lactate in human blood plasma
      samples with satisfactory results.

PMID- 21872078
TI  - A fluorescent "turn-on" probe for the dual-channel detection of Hg(II) and Mg(II)
      and its application of imaging in living cells.
AB  - A novel rhodamine-based fluorescent chemosensor (RND) was synthesized that
      contains two independent fluorophores and acts as a very sensitive, selective and
      reversible off-on probe for Hg(II). Importantly, this newly developed sensing
      system exhibited different fluorescent responses toward Hg(II) and Mg(II) at 589
      nm and 523 nm, respectively. RND also displayed detectable color change upon
      treatment with Hg(II). Results from confocal laser scanning microscopy
      experiments demonstrated that this chemosensor is cell permeable and can be used
      as a fluorescent probe for monitoring Hg(II) or Mg(II) in living cells. This
      probe can also indirectly detect glutathione (GSH) and cysteine (Cys) with good
      linear relationships.

PMID- 21872079
TI  - The effects of carbon nanotubes on the electrocatalysis of hydrogen peroxide by
      metallo-phthalocyanines.
AB  - The pre-grafted screen-printed gold electrode modified with phenyl-amino
      monolayer was investigated for covalent immobilization of phenyl-amine
      functionalized single-walled carbon nanotubes (PA-SWCNT) and metal tetra-amino
      phthalocyanine (MTAPc) using Schiff-base reactions with benzene-1,4
      dicarbaldehyde (BDCA) as cross-linker. The PA-SWCNT and MTAPc modified electrodes
      were applied as hybrids for electrochemical sensing of H(2)O(2). The step-by-step
      fabrication of the electrode was followed using electrochemistry, impedance
      spectroscopy, scanning electron microscopy and Raman spectroscopy and all these
      techniques confirmed the fabrication and the immobilization of PA-SWCNT, MnTAPc
      and CoTAPc onto gold surfaces. The apparent electron transfer constant (k(app))
      showed that the carbon nanotubes and metallo-phthalocyanines hybrids possess good
      electron transfer properties compared to the bare, pre-grafted and the MTAPc
      modified gold electrode surfaces without PA-SWCNT. The electrochemical sensing of
      hydrogen peroxide was successful with PA-SWCNT-MTAPc hybrid systems showing
      higher electrocatalytic currents compared to the other electrodes. The analytical
      parameters obtained using chronoamperometry gave good linearity at H(2)O(2)
      concentrations ranging from 1.0 to 30.0 MUmol L(-1). The values for the limit of
      detection (LoD) were found to be of the orders of 10(-7)M using the 3delta for
      all the electrodes. The PA-SWCNT-MTAPc modified SPAuEs were much more sensitive
      compared to PA-MTAPc modified SPAuEs.

PMID- 21872080
TI  - Determination of endocrine-disrupting compounds in water by carbon nanotubes
      solid-phase microextraction fiber coupled online with high performance liquid
      chromatography.
AB  - The commercial solid phase microextraction (SPME) fibers are not stable enough in
      organic solvent and tend to swell and strip off from the silica fiber in the high
      performance liquid chromatography (HPLC) mobile phase, and therefore the
      application of SPME coupled online with HPLC is limited. In this study, an SPME
      fiber coated with single walled carbon nanotubes (SWCNTs), prepared by means of
      electrophoretic deposition, was coupled on line to HPLC for the determination of
      four endocrine-disrupting compounds, i.e. bisphenol A (BPA), estrone (E(1)),
      17alpha-ethynylestradiol (EE(2)) and octylphenol (OP), in aqueous samples. The
      results showed that the SWCNTs coating on the prepared fiber did not swell and
      strip off from the platinum fiber throughout the experiment, thus indicating a
      high resistance to the HPLC mobile phase, the mixture of water and acetonitrile.
      The SWCNTs fiber had similar (for OP) or higher (for BPA, EE(2) and E(1))
      extraction efficiencies than the commonly used polyacrylate fiber, and had a
      lifetime of more than 120 operation times. Under the optimized conditions, the
      linearity of the proposed method was 1.0-30.0 MUg/L for BPA and OP and 3.0-90.0
      MUg/L for E(1) and EE(2). The limits of detection (LODs; S/N=3) and limits of
      quantification (LOQs; S/N=10) of the method were 0.32-0.52 MUg/L and 1.06-1.72
      MUg/L, respectively. Repeatability for one fiber (n=3) was in the range of 1.3
      7.1% and fiber-to-fiber reproducibility (n=3) was in the range of 1.6-8.4%. The
      proposed method was successfully applied for the analysis of spiked tap water and
      seawater samples with recoveries from 81.8 to 97.3%.

PMID- 21872081
TI  - NIR analysis of pharmaceutical samples without reference data: improving the
      calibration.
AB  - Using an appropriate set of samples to construct the calibration set is crucial
      with a view to ensuring accurate multivariate calibration of NIR spectroscopic
      data. In this work, we developed and optimized a new methodology for
      incorporating physical variability in pharmaceutical production based on the NIR
      spectrum for the process. Such a spectrum contains the spectral changes caused by
      each treatment applied to the component mixture during the production process.
      The proposed methodology involves adding a set of process spectra (viz.
      difference spectra between those for production tablets and a laboratory mixture
      of identical nominal composition) to the set of laboratory samples, which span
      the wanted concentration range, in order to construct a calibration set
      incorporating all physical changes undergone by the samples in each step of the
      production process. The best calibration model among those tested was selected by
      establishing the influence of spectral pretreatments used to obtain the process
      spectrum and construct the calibration models, and also by determining the
      multiplying factor m to be applied to the process spectra in order to ensure
      incorporation of all variability sources into the calibration model. The specific
      samples to be included in the calibration set were selected by principal
      component analysis (PCA). To this end, the new methodology for constructing
      calibration sets for determining the Active Principle Ingredients (API) and
      excipients was applied to Irbesartan tablets and validated by application to the
      API and excipients of paracetamol tablets. The proposed methodology provides
      simple, robust calibration models for determining the different components of a
      pharmaceutical formulation.

PMID- 21872082
TI  - Rapid detection of nitroaromatic and nitramine explosives on chromatographic
      paper and their reflectometric sensing on PVC tablets.
AB  - Rapid and inexpensive sensing of explosive traces in soil and post-blast debris
      for environmental and criminological purposes with optical sensors has recently
      gained importance. The developed sensing method for nitro-aromatic and nitramine
      based explosives is based on dropping an acetone solution of the analyte to an
      adsorbent surface, letting the solvent to dry, spraying an analytical reagent to
      produce a persistent spot, and indirectly measuring its reflectance by means of a
      miniature spectrometer. This method proved to be useful for on-site determination
      of nitro-aromatics (trinitrotoluene (TNT), 2,4,6-trinitrophenylmethylnitramine
      (tetryl) and dinitrotoluene (DNT)) and nitramines (1,3,5-trinitro-1,3,5
      triazacyclohexane (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine
      (HMX)) pre-adsorbed on a poly vinyl chloride (PVC) surface, with the use of
      different spray reagents for each group of explosives producing different colors.
      The calibration equations of the tested compounds as reflectance vs.
      concentration showed excellent linearity (correlation coefficient: 0.998-0.999).
      The linear quantification interval in terms of absolute quantity of analyte was
      0.1-0.5 MUg. The developed method was successfully tested for the analysis of
      military explosives Comp B and Octol, and was validated against high performance
      liquid chromatography (HPLC). The reflectometric sensing method could also be
      used for qualitative identification of the nitrated explosives on a
      chromatographic paper. The reagent-impregnated paper could also serve as sensor,
      enabling semi-quantitative determinations of TNT and tetryl.

PMID- 21872083
TI  - Antioxidant activity of grape skin aqueous extracts from pressurized hot water
      extraction combined with electron paramagnetic resonance spectroscopy.
AB  - Pressurized hot water extraction (PHWE) was employed to prepare extracts from
      dried grape skin of two wine grape varieties (St. Laurent and Alibernet) at
      various temperatures (from 40 up to 120 degrees C) and amounts of sample (0.5,
      1.0 and 1.5 g). To assess the antioxidant activity of the extracts, electron
      paramagnetic resonance (EPR) spectroscopy was applied involving DPPH and ABTS(+)
      assays. Other extract characteristics including HPLC profile of anthocyanins and
      total phenolic compound content were obtained as well. PHWE has also been
      compared with earlier results of extractions of the same grape skin samples with
      compressed methanol and compressed ethanol under the conditions of pressurized
      fluid extraction (PFE). From this comparison, PHWE emerges as the more benign and
      efficient extraction method to recover valuable phenolic antioxidants from grape
      skins for the prospective use in functional food supplements.

PMID- 21872084
TI  - Separation optimization in reversed-phase liquid chromatography by using alkanol
      additives in the mobile phase: application to amino acids.
AB  - In an effort to enhance complex mixture separations by using small amounts of a
      homologous series of alkanols as additives in the mobile phases, it was proposed
      an optimization algorithm based on a sixth-parameter retention model. This model
      considers simultaneously the contents of the main organic modifier and of the
      alkanol additive in the mobile phase as well as of the number of alkyl chain of
      the additive. This model is in fact a modification of a previously one derived in
      a recently published paper for the retention description of a mixture of purely
      hydrophobic alkylbenzenes under isocratic conditions with mobile phases
      containing alkanol additives. The effectiveness of the new retention model as
      well as the optimization algorithm was successfully applied to the separation of
      ten o-phthalaldehyde (OPA) derivatives of amino acids. Indeed, the new retention
      model exhibited an excellent prediction performance since the obtained overall
      predictive error between calculated and experimental times was only 2.8% for all
      isocratic runs by using a variety of mobile phase compositions containing any
      alkanol homologue even different than those used in the starting/fitting
      experiments. Moreover, a perfect resolution of the above amino acid mixture was
      achieved within only 7.4 min in the chromatogram recorded using the optimal
      mobile phase determined by means of the simple optimization algorithm proposed in
      this study.

PMID- 21872085
TI  - The burden of digestive diseases.

PMID- 21872086
TI  - Primary care providers. Preface.

PMID- 21872087
TI  - Peptic ulcer disease.
AB  - Peptic ulcer disease (PUD) is due mostly to the widespread use of low-dose
      aspirin and nonsteroidal anti-inflammator drugs. It occurs mostly in older
      patients and those with comorbidities. Pain awakening the patient from sleep
      between 12 and 3 a.m. affects two-thirds of duodenal ulcer patients and one-third
      of gastric ulcer patients. Older adults (>80 years old) with PUD often do not
      present with abdominal pain; instead, epigastric pain, nausea and vomiting are
      among their most common presenting symptoms.

PMID- 21872088
TI  - Selected disorders of malabsorption.
AB  - Malabsorption syndrome encompasses numerous clinical entities that result in
      chronic diarrhea, abdominal distention, and failure to thrive. These disorders
      may be congenital or acquired and include cystic fibrosis and Shwachman-Diamond
      syndrome; the rare congenital lactase deficiency; glucose-galactose
      malabsorption; sucrase-isomaltase deficiency; adult-type hypolactasia leading to
      acquired lactose intolerance. The pathology may be due to impairment in
      absorption or digestion of nutrients resulting in Nutritional deficiency,
      gastrointestinal symptoms, and extra gastrointestinal symptoms. Treatment is
      aimed at correcting the deficiencies and symptoms to improve quality of life.
      Common disorders of malabsorption celiac disease, pernicious anemia, and lactase
      deficiency are discussed in this article.

PMID- 21872089
TI  - Inflammatory bowel disease.
AB  - Crohn disease and ulcerative colitis are the most common forms of inflammatory
      bowel disease (IBD) likely to be encountered in primary care. Patient-centered
      care is essential for positive outcomes, and should include long-term continuity
      with an empathetic primary care provider who can provide skillful coordination of
      the requisite multidisciplinary approach. Early suspicion of the diagnosis and
      referral to expert gastroenterologists for confirmation and medical management is
      essential. Coordinating interdisciplinary consultations, including colorectal
      surgeons, radiologists, stoma therapists, psychologists, and rheumatologists, in
      combination with comprehensive patient education, is key to decreasing overall
      morbidity, mortality, and health care costs associated with IBD.

PMID- 21872090
TI  - Irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that leads
      to crampy pain, gassiness, bloating, and changes in bowel habits in the absence
      of any currently identifiable organic disorder. Patients with IBS may be
      classified by their predominant bowel habit: diarrhea-predominant, constipation
      predominant, or IBS with alternating bowel movements. IBS is often associated
      with stress or anxiety. Although IBS can be frustrating and concerning to
      patients with this disorder, it does not cause permanent harm to the intestines
      and does not lead to a serious disease such as cancer. Although treatments exist
      for its symptoms, there is no known cure.

PMID- 21872091
TI  - Screening for cancerous and precancerous conditions of the colon.
AB  - Five points for the primary care physician: 1. Colorectal cancer (CRC) is the
      second leading cause of cancer-related death in both men and women in the United
      States. 2. Guidelines recommend initiating CRC screening in average-risk patients
      at age 50 years, but in African Americans at age 45 years. 3. It is preferred
      that an informed decision is made by the patient with the help of their clinician
      about the type of screening test based on the patient's personal preferences. 4.
      Patients with personal history of chronic ulcerative colitis and Crohn colitis
      have significant cancer risk 8 years after the onset of pancolitis or 12 to 15
      years after the onset of left-sided colitis. Colonoscopy every 1 to 2 years
      should be performed, with biopsies for dysplasia. 5. Counseling to consider
      genetic testing and early screening recommendations for those with personal or
      family history of familial adenomatous polyposis or hereditary nonpolyposis
      colorectal cancer.

PMID- 21872092
TI  - Diagnostic approach to the patient with jaundice.
AB  - Jaundice is caused by many disease processes ranging from benign to life
      threatening. History and physical examination remain important tools in
      evaluating the etiology of jaundice. The conjugation state of bilirubin, along
      with other laboratory tests judiciously ordered, can guide the provider toward
      category of illness. Hyperbilirubinemia may be categorized as to its etiology:
      unconjugated/prehepatic, intrahepatic, or extrahepatic/obstructive. Referral
      should be considered when likelihood of malignancy, chronic autoimmune condition,
      or need for intervention exists.

PMID- 21872093
TI  - Care of chronic liver disease.
AB  - Regardless of etiology, chronic liver disease generally involves a process of
      progressive destruction and regeneration of the liver parenchyma, leading to
      fibrosis and cirrhosis. At an early stage, most patients are asymptomatic and can
      easily go undiagnosed and untreated. Primary care physicians can often make the
      diagnosis but may offer little treatment. Better understanding about treatment is
      the key for primary care providers to provide better care for this group of
      patients. This review focuses on the treatment of the most common causes of
      chronic liver disease, including hepatitis B, hepatitis C, alcoholic cirrhosis,
      nonalcoholic fatty liver disease, and hemochromatosis.

PMID- 21872094
TI  - Primary care of the liver transplant recipient.
AB  - Chronic rejection of liver graft is an insidious process. Major immunosuppression
      medications such as tacrolimus, cyclosporin, and sirolimus have dose-related
      toxicity and narrow therapeutic windows. Certain drugs can affect metabolism of
      calcineurin inhibitors. Primary care physicians should be vigilant for any
      unusual opportunistic infection in liver transplant recipients. The quality of
      life of liver transplant recipients is an important aspect of care by primary
      care physicians. Alcohol relapse and possibility of depression in liver
      transplant recipients should be a continuous concern for primary care physicians.
      This article provides a guideline for the care of liver transplant recipients.

PMID- 21872095
TI  - Chronic pancreatitis and exocrine insufficiency.
AB  - The evaluation, management, and follow-up of patients with chronic pancreatitis
      (CP) can be simple, but it can also be complex, so having a good referral network
      of subspecialists experienced in this field is essential. Identifying the cause
      of CP requires a systematic review of the many potential causes when the cause is
      not obvious. The identification of patients with autoimmune CP is particularly
      important because treatment with steroids may be effective. Alterations in pain
      or other symptoms in patients with CP should not be attributed to worsening
      disease before evaluations for complications including malignancy are done.

PMID- 21872096
TI  - Acute infectious diarrhea.
AB  - Infectious diarrhea is both a local and a global concern. Illnesses can range
      from mild inconveniences to life-threatening epidemics. Although diarrhea can be
      caused by a vast array of pathogens, the cornerstone of prevention is provision
      of a safe food and water supply, application of basic hygiene principles, and the
      development and administration of vaccines. The cornerstone of treatment is
      rehydration. Selection of specific antimicrobial therapy should be based on
      disease presentation and epidemiologic factors.

PMID- 21872097
TI  - Vertical locking of the metacarpophalangeal joint in young adults.
AB  - Locking of the metacarpophalangeal joints has been occasionally reported in older
      adults, but reports of this problem are rare in younger individuals. We report 8
      young adult patients with a metacarpophalangeal joint locked in 90 degrees 
      flexion after minor trauma. The cases included 6 little fingers and 2 thumbs in 1
      male and 7 female patients aged 16 to 39 years. All were easily reduced closed.
      We postulate the mechanism of injury.

PMID- 21872098
TI  - Complex regional pain syndrome of the upper extremity.
AB  - The diagnosis and management of complex regional pain syndrome is often
      challenging. Early diagnosis and intervention improve outcomes in most patients;
      however, some patients will progress regardless of intervention.
      Multidisciplinary management facilitates care in complex cases. The onset of
      signs and symptoms may be obvious or insidious; temporal delay is a frequent
      occurrence. Difficulty sleeping, pain unresponsive to narcotics, swelling,
      stiffness, and hypersensitivity are harbingers of onset. Multimodal treatment
      with hand therapy, sympatholytic drugs, and stress loading may be augmented with
      anesthesia blocks. If the dystrophic symptoms are controllable by medications and
      a nociceptive focus or nerve derangement is correctable, surgery is an
      appropriate alternative. Chronic sequelae of contracture may also be addressed
      surgically in patients with controllable sympathetically maintained pain.

PMID- 21872099
TI  - Artecoll injections or something else?

PMID- 21872100
TI  - Biomechanical evaluation of flexor tendon repair using barbed suture material: a
      comparative ex vivo study.

PMID- 21872101
TI  - Caution against percutaneous trigger release in patients on anticoagulant.

PMID- 21872102
TI  - A public health culture in the ED.

PMID- 21872103
TI  - Comment: "Quantitative insulin and C peptide levels among ED patients with
      sulfonylurea-induced hypoglycemia".

PMID- 21872104
TI  - Estimating the clinical impact of bringing a multimarker cardiac panel to the
      bedside in the ED.

PMID- 21872106
TI  - Industry relations.

PMID- 21872107
TI  - Conflict of interest and the Society for Vascular Surgery.
AB  - Specialty medical societies such as Society for Vascular Surgery (SVS) are
      instrumental in the development and dissemination of medical knowledge through
      scientific presentations, publication of rigorously peer-reviewed writings,
      awarding competitive research and training grants, and the provision of high
      quality continuing medical education (CME). It is vital that in these roles the
      SVS remain in fact and in perception completely free of all influence and bias
      from industry. While independence from bias has always been necessary, the
      increasing focus by governmental agencies, industry organizations, and society
      has made it important for the SVS to address this issue in a formal way. In June
      2010, the SVS Board of Directors approved a set of guidelines specifically
      designed to address management of conflict of interest among its members and its
      leaders. These guidelines, included in this article, were based on currently
      available information and policies put forth by legislative bodies, academic
      medical centers, industry groups, and other professional medical societies, and
      were designed to safeguard against abuse while maintaining valuable collaboration
      between vascular surgeons and their industry partners. The guidelines are
      included in this article.

PMID- 21872108
TI  - Restrictions on interactions between doctors and industry could ultimately hurt
      patients.
AB  - Physician-industry collaboration has led to a diverse array of therapeutic
      advancements that have benefitted a broad spectrum of patient populations.
      Evolving regulations, both institutional and governmental, aiming to govern
      interactions between physicians and pharmaceutical and medical device
      manufacturers have become increasingly prevalent. Emerging data suggest that
      restrictions on physician-industry collaboration have the potential to harm
      patient care by degrading innovation and stifling medical education. The
      following article reviews the effects of legislation on medical innovation as
      well as the impact on continuing medical education.

PMID- 21872109
TI  - Private practice perspective on conflict of interest mandates.
AB  - This article assesses the current mandates on conflict of interest issues as they
      affect the practice of community-based vascular surgery and the pharmaceutical
      and medical technology industries and expresses the views of a private practice
      vascular surgeon. Scenarios where conflict of interest may occur are presented
      with assessments on how these scenarios will play out if such mandates are
      enforced.

PMID- 21872110
TI  - Academic medical centers write their own rules.
AB  - The interaction between pharmaceutical and device companies and hospitals and
      physicians has undergone significant transformation in the past few years due to
      the public's perception that bias may result when such relationships are not
      disclosed and monitored. Policies need to be written by medical centers and
      hospitals to preserve and retain the trust of the public. The policy written by
      Johns Hopkins Medical Institutions is outlined and its implications discussed in
      this article. The importance of such policies in guiding young faculty and staff
      as they begin their careers cannot be overemphasized.

PMID- 21872111
TI  - Shining the light on physician-pharmaceutical and medical device industry
      financial relationships.
AB  - Long subject to legal scrutiny under the federal Anti-Kickback Statute, financial
      ties between physicians and drug manufacturers have recently come under
      additional pressure as a result of recently enacted state and federal disclosure
      laws and state gift restrictions, the latest coming in connection with the
      Federal Health Reform Law. These "sunshine" laws have been motivated by the
      concern that gifts and payments by manufacturers to physicians may lead to
      conflicts of interest and improperly influence physicians in their drug- or
      device-prescribing decisions. As a backdrop to these new laws, it is helpful to
      review prior guidance regarding manufacturer-physician financial relationships,
      both from the federal government and the industry itself. These laws do not
      prohibit physician involvement with industry in research and education, but they
      impose various new compliance requirements on these relationships, and also in
      many cases, require public disclosure of arrangements that previously were
      treated as confidential. It is still too early to tell if these laws will stifle
      innovation, but they do require a heightened degree of diligence to avoid, at a
      minimum, adverse publicity and embarrassment and, at worst, criminal and civil
      liability.

PMID- 21872112
TI  - New paradigms for physician-industry relations: overview and application for SVS
      members.
AB  - Relationships between physicians and their industry partners have ranged from
      spectacular collaborations that produce extraordinary advances in patient care,
      such as endovascular aneurysm repair, to humiliating scandals such as extravagant
      trips and bogus "consulting" agreements resulting in legal actions. It is the
      latter which have led many to call for the end of all physician-industry
      relationships, and the former which mandate their preservation. While these two
      examples are representative of extremes at each end of the spectrum of this
      issue, in reality the majority of physician-industry relationships are far more
      complex, and the line between appropriate and inappropriate, and ethical and
      unethical, is hard to draw. The benefits of our relationships with industry are
      many: partnering to develop new therapies and technologies, educating and
      training physicians around new therapies and technologies, support of continuing
      medical education (CME), fellowship training, and patient education. The pitfall
      and danger of this relationship is that support from industry, be it a meal, a
      pen, an educational grant, or flattery, may unduly and inappropriately influence
      physician decision making around a specific company's product. While it is clear
      that free trips are not within the realm of proper interaction, what about
      unrestricted educational grants to institutions, or support of CME activities,
      professional society meetings, and new device training? As a result of the
      intense scrutiny of relationships between physicians and industry recently,
      multiple diverse entities (Association of American Medical Colleges, American
      Medical Association, Accreditation Council for Continuing Medical Education,
      professional medical associations, academic medical centers, industry, and
      government) have generated guidelines and policies with very different
      perspectives, reflective of their different missions. These policies range from
      vague and lenient, with only basic limitation of the physician-industry
      relationship, to extremely rigid and strict, with only minimal interaction and
      mission support permitted. Given the many changes in oversight and expectations
      for the relationship between physicians and industry, it is important for
      vascular surgeons to be aware of the background behind these modifications, the
      evidence that they are needed, and the positions of the diverse organizations and
      institutions that have already defined their policies on this issue.

PMID- 21872113
TI  - Managing perceived conflicts of interest while ensuring the continued innovation
      of medical technology.
AB  - If it were not for the ongoing collaboration between vascular surgeons and the
      medical technology industry, many of these advanced treatments used every day in
      vascular interventional surgery would not exist. The flip side of this coin is
      that these vital relationships create multiple roles for surgeons and must be
      appropriately managed. The dynamic process of innovation, along with factors such
      as product delivery technique refinement, education, testing and clinical trials,
      and product support, all make it necessary for ongoing and close collaboration
      between surgeons and the device industry. This unique relationship sometimes
      leads to the perception of conflicts of interest for physicians, in part because
      the competing pressures from the multiple, overlapping roles as
      clinician/caregiver/investigator/innovator/customer are significant. To address
      this issue, the Advanced Medical Technology Association (AdvaMed), the nation's
      largest medical technology association representing medical device and
      diagnostics companies, developed a Code of Ethics to guide medical technology
      companies in their interactions with health care professionals. First introduced
      in 1993, the AdvaMed Code strongly encourages both industry and physicians to
      commit to openness and high ethical standards in the conduct of their business
      interactions. The AdvaMed Code addresses many of the types of interactions that
      can occur between companies and health care professionals, including training,
      consulting agreements, the provision of demonstration and evaluation units, and
      charitable donations. By following the Code, companies send a strong message that
      treatment decisions must always be based on the best interest of the patient.

PMID- 21872114
TI  - The new CMSS code for interactions with companies managing relationships to
      minimize conflicts.
AB  - Conflicts of interest in medicine have received significant attention in recent
      years, through the public and professional media, federal and state governments,
      and through a 2009 report of the Institute of Medicine on Conflict of Interest in
      Medical Research, Education and Practice. The Council of Medical Specialty
      Societies (CMSS) Code for Interactions with Companies was adopted by the CMSS in
      April 2010. The Code guides specialty societies in the profession of medicine in
      ethical relationships between societies and the pharmaceutical and medical device
      industries. The Code serves to protect and promote the independence of specialty
      societies and their leaders in corporate sponsorships, licensing, advertising,
      society meetings, exhibits, educational programs, journals, clinical practice
      guidelines, and research.

PMID- 21872115
TI  - Industry working with physicians through professional medical associations.
AB  - The physician/surgeon's interactions with industry have come under scrutiny in
      recent years for several reasons. Although some think that the professional
      medical association or society may provide an avenue to allow such interactions
      with less risk, there are concerns and challenges for such organizations as it
      relates to ethical and professional norms of their members. This is one surgeon's
      review of some pertinent information regarding what the professional medical
      society provides to its members and what role industry plays in the society's
      ability to provide these benefits. There is an exploration of the risks involved
      and practical methods to control inherent conflicts of interest involved in this
      interaction.

PMID- 21872116
TI  - Industry and the profession of medicine: balancing appropriate relationships with
      the need for innovation.
AB  - Much has been made over the last few years about conflicts of interest in the
      health care community's relationships with industry members, including individual
      physicians, academic medical centers, and professional organizations. Not only
      has the Department of Justice (DOJ) been investigating questionable
      relationships, but House and Senate Oversight Committees have also weighed in on
      real and perceived conflicts. Most recently, the Physician Payments Sunshine Act
      of 2010 requires companies to begin recording any physician payments, including
      stock options, research grants, knickknacks, consulting fees, and travel to
      medical conferences that are worth more than ten dollars in 2012 and report them
      on March 31, 2013. To date, the American College of Cardiology (ACC) has
      developed and instituted one of the most stringent policies in the medical
      community to ensure that support from industry has no influence on any of its
      clinical documents. Furthermore, the need for the ACC's "Principles for
      Relationships with Industry," the organization's guide in nine key operational
      areas, are critical given that, when it comes to industry, properly managed
      partnerships are absolutely essential to maintaining scientific progress in
      cardiology and other specialties. The ACC relies on industry funding to advance
      cardiovascular research, as well as cardiovascular workforce training,
      practitioner diversity, medical education, and life-long learning. Without this
      funding, the ACC's ability to provide meaningful, unbiased education and to
      improve quality of care would be far more limited than that which is currently
      offered to its members and, ultimately, patients. Rather than restricting
      industry funding for such activities, the focus should instead be on transparency
      and actively and appropriately managing industry relationships. Ethical and
      appropriate partnerships with industry can prove beneficial in funding of
      education, research, and quality improvement activities. In addition, they are
      critical in the advancement of the quality of care for patients. The challenge is
      for medical societies to help the media, the public, and policymakers better
      understand the role of industry in promoting research, education, and innovation
      in medicine.

PMID- 21872117
TI  - Conflict of interest issues pertinent to Veterans Affairs Medical Centers.
AB  - Conflicts of interest exist when an arrangement potentially exerts inappropriate
      influence on decision making or professional judgment, or is perceived to do so,
      and can thus damage the public trust and undermine the integrity of those
      decisions. Concerns regarding financial conflicts of interest in the medical
      arena have reached their height as of late, given that physicians now function in
      a milieu of complex and delicate relationships with pharmaceutical,
      biotechnology, and medical device industries. Even when such relationships do not
      correlate with actual compromise of judgment or patient care, it threatens the
      credibility of both the health care professional and the institution because of
      the social perception of the effect of these relationships. Although most
      institutions in the Western world set forth a code of ethics and conflict-of
      interest policies to be followed under threat of termination, the Veterans Health
      Administration (VHA) presents itself as a unique environment in which conflicts
      of interest are subject to governmental laws, violation of which may not only
      result in employment-related discipline, but may be sanctioned by civil and
      criminal penalties. Moreover, these provisions are developed by a national
      authoritative organization rather than being institution-specific guidelines.
      Given that many academic physicians working within the VHA may also have a
      component of their practice in a University setting, it becomes important to
      understand the differences in policy between these contexts so as not to threaten
      the public trust in the veracity of decisions made and, therefore, maintain the
      integrity of the relationship between physician and patient. This article will
      review aspects of conflict-of-interest policies in the realm of research,
      financial relationships, foreign travel, and vendor contracting that are
      particular to the VHA and make it a unique environment to function in as a
      physician and scientist.

PMID- 21872118
TI  - Author disclosure of conflict of interest in vascular surgery journals.
AB  - OBJECTIVES: Advances in vascular surgery are increasingly technology-driven, and
      the relationships between surgeons and the medical device industry can be
      complex. This study reviewed conflict of interest (COI) disclosure in the
      vascular surgery journals regarding several selected technology-driven topics,
      including endovascular stent grafts (EV), carotid artery stenting (CAS), and
      peripheral arterial interventions (PI), to suggest further directions. METHODS:
      Authors' COI disclosures were reviewed from all clinical papers published in 2008
      and 2009 in each of six vascular surgery journals, and pertaining to three
      selected topics (EV, CAS, and PI). Rate of COI disclosure was evaluated as a
      function of journal, topic, article type (randomized trial, case series, case
      report, review, or meta-analysis), and authors' region of origin. Secondarily,
      consistency of authors' disclosure was evaluated by reviewing papers by the same
      author and of the same topic. RESULTS: Six hundred thirty-five papers were
      reviewed from the six journals. A COI was declared in 125 (19.7%) of these
      papers. This rate differed between journals (range, 3.2%-34.1%; P < .0001). Rate
      of disclosure did not differ between topics (range, 12.8%-21.2%; P = .12),
      article type (range, 14.7%-30%; P = .28), or region of origin (range, 0%-33.3%; P
      = .09). There were 116 instances of the same author writing papers describing the
      same general topic. COI disclosure was consistent in the majority of these
      instances (72.4%), but inconsistent in 32 cases (27.6%). The most common (P =
      .006) inconsistencies involved the same type of article in different journals
      (46.9%), or in the same journal (25%). CONCLUSIONS: Rates of disclosure of COI,
      and inconsistencies in disclosure in the vascular surgery literature are at least
      partially due to differences in journals' reporting policies, while a smaller
      proportion of these inconsistencies are due to individual author behavior.
      Journals should adopt a consistent requirement for a separate COI declaration
      where all relevant financial arrangements are disclosed.

PMID- 21872119
TI  - Conflicts of interest for medical publishers and editors: protecting the
      integrity of scientific scholarship.
AB  - Competition of interest may exist at all levels in the medical publication
      process. Ensuring the integrity of scientific scholarship involves protecting
      editorial independence, promoting the use of scientific arbitration boards,
      promoting transparency throughout all stages of publication, and protecting the
      relationship between the publisher and its editors through an effective legal
      framework. It is incumbent upon the publisher, editors, authors, and readers to
      ensure that the highest standards of scientific scholarship are upheld. Doing so
      will help reduce fraud and misrepresentation in medical research and increase the
      trustworthiness of landmark findings in science.

PMID- 21872120
TI  - Evaluation of magnetic resonance imaging criteria for Meckel's cave lesion:
      logistic regression analysis and correlation with surgical findings.
AB  - OBJECTIVE: Our aim was to investigate the statistical preoperative diagnostic
      criteria of lesions of Meckel's cave (MC) on MRI. MATERIALS AND METHODS: We
      retrospectively reviewed the MR images with MC lesions in 34 patients. The MR
      signs were compared with histopathologic and surgical findings in all lesions.
      Odds ratio values and the confidence intervals of the MRI diagnostic criteria
      were evaluated by univariate logistic regression. RESULTS: The following three
      signs of MC on post-contrast T1WI of MRI have been found to represent the most
      valuable criterion for determination of MC lesion: (1) contrast enhancement, (2)
      bulging of lateral wall, and (3) the absence of normal MC, with odds ratios of
      362.67 (P<.001), 40.38 (P = .001), and 40.38 (P = .001) individually. CONCLUSION:
      Contrast enhancement on post-contrast T1WI is the most sensitive MR sign for
      demonstrating the presence of MC lesion.

PMID- 21872121
TI  - Comparison of full-field digital mammography workstation and conventional picture
      archiving and communication system in image quality and diagnostic performance.
AB  - The object of this study was to compare of full-field digital mammography (FFDM)
      workstation and conventional picture archiving and communication systems (PACS)
      in image quality and diagnostic performance. We assembled 80 masses and 80
      microcalcifications. Images were displayed on workstation, 5M, and 3M PACS
      monitors. The image quality for mammograms on workstation was significantly
      better than that for mammograms on PACS monitors. The sensitivity and NPV for
      microcalcifications on workstation were higher than those on PACS monitors. The
      conventional PACS cannot substitute for a FFDM workstation for mammographic
      evaluation.

PMID- 21872123
TI  - Improved visualization of tubes and lines in portable intensive care unit
      radiographs: a study comparing a new approach to the standard approach.
AB  - Tube and line interpretation in portable chest radiographs was assessed using a
      new visualization method. When using the new method, radiologists' interpretation
      time was reduced by 30% vs. standard modality processing and window and level (23
      vs. 33 s). For pulmonary ICU physicians, reading time was essentially unchanged.
      There was more than a 50% reduction in the use of inferential language in the
      dictation for both reader groups when using the new method, suggesting greater
      interpretation confidence.

PMID- 21872122
TI  - Diagnostic performance in differentiation of breast lesion on digital mammograms:
      comparison among hard-copy film, 3-megapixel LCD monitor, and 5-megapixel LCD
      monitor.
AB  - We compared observer performance of digital mammography among hard-copy readings
      and soft-copy readings using 3-megapixel (3M) and 5-megapixel (5M) liquid crystal
      display (LCD) monitors. Five experienced radiologists assessed 80 mammograms of
      40 cancers and 40 benign lesions. There were no significant differences among the
      average A(z) of three modalities and among the kappa values for intra- and
      interobserver agreement. The soft-copy reading using the 3M LCD monitor took a
      slightly longer time, although there were no significant differences.

PMID- 21872124
TI  - Upper gastrointestinal tract heterotopic pancreas: findings from CT and
      endoscopic imaging with histopathologic correlation.
AB  - OBJECTIVE: To evaluate and describe computed tomographic (CT) and endoscopic (ES)
      imaging findings in patients with pathologically confirmed upper gastrointestinal
      (GI) tract heterotopic pancreas (HP). METHODS: Findings from imaging examinations
      in 11 patients with pathologically confirmed HP were retrospectively reviewed (CT
      images obtained from 11 patients and ES images from 6 patients were available for
      review). Two radiologists evaluated lesion location, size, shape and border as
      well as growth pattern, enhancement pattern, enhancement grade and number of
      tumors. The presence of surface dimpling, prominent enhancement of overlying
      mucosa, and low intralesional attenuation were also evaluated. RESULTS: HP in the
      upper GI tract showed typical features in CT imaging: submucosal masses, ill
      defined borders, endoluminal growth patterns, bright enhancement similar to the
      normal pancreas, surface dimpling and low intralesional attenuation. Endoscopic
      photographs manifested an endoluminal, ill-defined, submucosal mass in the upper
      GI tract wall, typically with central umbilication. The LD (long diameter)/SD
      (short diameter) ratios were found to be significantly different between HP in
      the stomach and HP in the duodenum (P<.05 for each finding). In addition, HP in
      the duodenum tended to be small and round. CONCLUSIONS: HP exhibits typical
      pancreatic pathologic features. Images showed characteristic features in CT
      imaging: submucosal masses, ill-defined lesions with an endoluminal growth
      pattern, bright enhancement similar to the normal pancreas, surface dimpling and
      low intralesional attenuation. ES imaging showed an endoluminal, ill-defined,
      submucosal mass, typically with central umbilication.

PMID- 21872125
TI  - Evaluation of an MRI-based score of disease activity in perianal fistulizing
      Crohn's disease.
AB  - To evaluate a magnetic resonance imaging (MRI)-based score of disease severity
      for perianal fistulizing Crohn's disease (CD), 16 patients with perianal
      fistulizing CD underwent 1.5-T MRI before and after infliximab therapy. MRI
      scores, Perianal Disease Activity Index (PDAI) and C-reactive protein (CRP) were
      calculated, and fistula drainage was assessed. These items were compared for
      responders and nonresponders. After therapy, PDAI values and CRP values decreased
      significantly in responders, but there were no significant differences in the MRI
      scores. In all responders, MRI findings were indicative of persisting active
      inflammation. In these patients, a relapse rate of 57% was seen.

PMID- 21872127
TI  - Extrafetal findings at fetal MR: evaluation of the normal placenta and
      correlation with ultrasound.
AB  - Despite the increasing use of magnetic resonance (MR) for fetal imaging, few
      studies have addressed the MR appearance of the normal placenta. The goal of this
      paper is to describe the MR features and thickness of the normal placenta during
      the second and early third trimester of gestation, based on a retrospective study
      comparing MR with the reference standard of obstetric imaging, ultrasound.

PMID- 21872126
TI  - Screening for liver metastases in women with mammary carcinoma: comparison of
      contrast-enhanced ultrasound and magnetic resonance imaging.
AB  - OBJECTIVE: The objective of the present study was to compare conventional B-mode
      ultrasound (BMU), contrast-enhanced ultrasound (CEUS), and magnetic resonance
      imaging (MRI) in the detection of liver metastases at the primary staging and
      follow-up of women with histologically confirmed mammary carcinoma. PATIENTS AND
      METHODS: Included in the study were 55 women (aged 57.5 +/- 11.0 years, range 27
      75 years; mean disease duration 57.5 months, range 5-168 months); of these, 17
      women were examined as part of primary staging (staging group) and 38 women at
      follow-up (follow-up group). All patients underwent BMU (Philips HDI 5000), CEUS
      (Philips HDI 5000; 4.8 ml SonoVue), and MRI (Siemens Avanto 1.5 T) of the liver.
      RESULTS: In the staging group (n = 17), a mass was detected by BMU in 24% (n =
      4), by CEUS in 29% (n = 5), and by MRI in 47% (n = 8); masses suspicious for
      malignancy were identified in 6% of patients with BMU and in 12% each by CEUS and
      MRI. Malignancy was not confirmed in any case by cytology or surgery. In the
      follow-up group (n = 38), masses were identified by MRI in 53% of patients with
      suspicion of malignancy in 18%. Malignancy was confirmed in 16% of cases
      identified at MRI, in 13% of cases identified with CEUS, and in 11% of cases
      identified with BMU. The Pearson coefficients of correlation were r = .29 (P =
      .03) for MRI vs. BMU; r = .42 (P = .002) for MRI vs. CEUS; and r = .75 (P <=
      .001) for BMU vs. CEUS. With respect to malignancy, the Pearson coefficients of
      correlation were r = .40 (P = .099) for BMU vs. MRI and r = .71 (P = .0009) for
      CEUS vs. MRI. CONCLUSIONS: Beginning in tumor stage III, the use of CEUS and MRI
      is associated with a significantly greater benefit in the detection of malignant
      tumors of the liver compared with conventional BMU. BMU appears to be adequate
      for primary staging and the follow-up of lower tumor stages.

PMID- 21872128
TI  - Prevalence of shoulder enchondromas on routine MR imaging.
AB  - The objective of this study was to examine the prevalence of incidental shoulder
      enchondromas on routine magnetic resonance (MR) shoulder imaging. Consecutive
      routine shoulder MR examinations (N = 477) performed for suspected internal
      derangement were reviewed for the presence of incidental enchondromas. Incidental
      enchondromas were detected on 2.1% of routine MR shoulder examinations, the vast
      majority abutting the physeal plate. This prevalence is important to appreciate,
      in order to form a meaningful differential diagnosis of pathologic proximal
      humerus lesions.

PMID- 21872129
TI  - Dynamic T1 functional MRI examinations with use of blood pool contrast agent--an
      approach to optimization of the technique.
AB  - The goal was to optimize dynamic T1 imaging for functional MRI (fMRI)
      examinations. For each of the 10 healthy subjects T1 3D gradient echo sequence
      (GRE) sequences were provided immediately after administration of blood pool
      contrast agent then every 2 h when subjects performed block finger tapings.
      Dynamic T1 fMRI is sensitive to detect cortical activations up to 6 h after BPCA
      administration. fMRI should be conducted within 2 h of CA administration, which
      is enough time for a typical fMRI experiment procedure.

PMID- 21872130
TI  - Intracranial dural metastatic prostate cancer can mimic meningioma: a report of
      two cases.
AB  - Cerebral metastases from any malignancy, including prostate carcinoma, may
      present as a meningeal mass, and differentiating the lesion from a meningioma can
      be challenging. We report the clinical and neuroimaging features of two patients
      with dural metastases from prostate carcinoma and discuss differentiation of
      metastatic lesions from meningioma. In both patients, it appeared that the
      prostate carcinoma had been successfully treated, and neither patient was found
      to have any other metastases at the time of diagnosis of the dural lesions.

PMID- 21872131
TI  - Acquired left coronary artery fistula draining to the cardiac vein system after
      acute myocardial infarction revealed by CT scan.
AB  - Coronary artery fistula (CAF) is a congenital condition characterized by a
      pathological communication between a coronary artery and a systemic vein or one
      of the cardiac chambers. Iatrogenic CAFs were reported to develop secondary to
      the rupture of coronary aneurysm. Instances of acquired CAF draining into the
      cardiac chambers have been described after acute myocardial infarction.
      Angiography is the gold standard in diagnosing CAF. We describe the case of a
      patient who developed a fistula draining into the middle cardiac vein on the
      posterior interventricular sulcus, after acute myocardial infarction, revealed by
      CT scan.

PMID- 21872132
TI  - Dermatofibrosarcoma protuberans of the breast: a case report.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon mesenchymal tumour of the
      dermis and subcutis, which most commonly appears on the body and the extremities.
      Its occurrence in the breast is rare, and when it does, it can mimic a primary,
      benign breast lesion. We present a case of DFSP over the breast of a patient
      together with the associated imaging findings that can potentially help us
      differentiate this tumour from a primary breast lesion. The awareness of this
      entity allows a prompt diagnosis to be made and the disease to be properly
      managed.

PMID- 21872133
TI  - Benign metastasizing leiomyoma of the lung with malignant transformation
      mimicking mediastinal tumor.
AB  - We report a rare case of benign metastasizing leiomyomas (BMLs) showing malignant
      transformation in one of them. A 65-year-old woman had a fever. Computed
      tomography (CT) revealed a mass on the left side of the anterior mediastinum and
      multiple nodules in bilateral lungs. The masses proved to be leiomyomas and a
      leiomyosarcoma. The latter showed heterogeneous contrast enhancement on CT and
      high heterogeneous uptake of (18)F-fluorodeoxyglucose (FDG) on positron emission
      tomography (PET)-CT. This case suggested the potential usefulness of PET-CT for
      differentiating these entities.

PMID- 21872134
TI  - Nonspecific FDG uptake in the tongue mimicking the primary tumor in a patient
      with cancer of unknown primary.
AB  - For cancers of the head and neck, the combination of (18)F-fluorodeoxy-glucose
      positron emission tomography (FDG-PET)/computed tomography (CT) gains wide
      acceptance, especially if the primary tumor is unknown (CUP). A patient underwent
      FDG-PET/CT for squamous cell CUP with cervical lymph node metastases. FDG-PET/CT
      showed uptake in the right side of the tongue, rendering this area a possible
      location for the primary tumor. However, clinical examination revealed a
      deviation of the tongue toward the left side indicating affection of the left
      hypoglossal nerve, causing the increased FDG uptake. This case illustrates the
      interpretive pitfalls of unspecific FDG uptake in PET/CT imaging of the head and
      neck.

PMID- 21872135
TI  - Use of nanoparticles for pharmaceutical dosage forms.

PMID- 21872137
TI  - Where have all the clinical trials gone?

PMID- 21872138
TI  - Comparative long term effects of nebivolol and carvedilol in hypertensive heart
      failure patients.
AB  - BACKGROUND: Beta-blockers improve left ventricular (LV) systolic function and
      prognosis in patients with chronic heart failure (CHF), but their different
      pleiotropic properties may influence their cardiovascular effects. This open
      label study compared the effects of long-term treatment with nebivolol versus
      carvedilol on LV ejection fraction (LVEF), in hypertensive CHF patients.
      Secondary end points were to assess the effect of the 2 beta-blockers on exercise
      capacity and clinical outcome. METHODS AND RESULTS: A total of 160 hypertensive
      CHF patients, with LVEF <40% and in New York Heart Association (NYHA) functional
      class I, II, or III, were randomly assigned to receive nebivolol or carvedilol
      for 24 months. At baseline and at the end of treatment, all patients underwent
      clinical evaluation, echocardiography, and 6-minute walking test. The target
      doses were 10 mg/d for nebivolol and 50 mg/d for carvedilol. Compared with
      baseline values, LVEF increased by a similar extent in the carvedilol (C) and
      nebivolol (N) groups (C from 36.1% (SD 1.5%) to 40.9% (SD 1.9%), P < .001; N from
      34.1% (SD 1.8%) to 38.5% (SF 2.2%), P < .001). Heart rate and NYHA functional
      class decreased significantly in both groups, and the 6-minute walking distance
      increased (C from 420 m (SD 104 m) to 490 m (SD 115 m), P < .001; N from 421 m
      (SD 118 m) to 487 m (SD 138 m), P < .001). During 24 months, 21 carvedilol
      recipients (26%) and 18 nebivolol recipients (22%) had cardiac events, including
      3 and 4 deaths, respectively. CONCLUSION: In the long term, nebivolol and
      carvedilol appear to be similarly effective in the treatment of hypertensive
      patients with CHF.

PMID- 21872140
TI  - Noninvasive monitoring of left ventricular end-diastolic pressure reduces
      rehospitalization rates in patients hospitalized for heart failure: a randomized
      controlled trial.
AB  - BACKGROUND: In patients admitted for heart failure (HF), unrecognized elevation
      of left ventricular end-diastolic pressure (LVEDP) at the time of discharge may
      have a role in the high rehospitalization rate for HF on follow-up. METHODS AND
      RESULTS: In a small, prospective study (n = 50), patients admitted for HF were
      randomized to management guided by daily noninvasive estimated LVEDP monitoring
      (Group I, open) to a target LVEDP of <20 mm Hg or management based on clinical
      assessment alone without knowledge of the estimated LVEDP (Group II, blinded).
      Noninvasive estimated LVEDP was measured by the VeriCor monitor, which uses the
      Valsalva maneuver to derive the LVEDP. The primary endpoints were the reduction
      of estimated LVEDP at discharge and the HF rehospitalization rate on follow-up.
      Estimated LVEDP was significantly reduced at discharge in the open group compared
      with the blinded group (mean estimated LVEDP 19.7 +/- 1.3 mm Hg vs 25.6 +/- 1.5
      mm Hg, respectively, P = 0.01). The rehospitalization rates for HF on follow-up
      were significantly improved in the open group compared with the blinded group (at
      1 month: 0% vs 25%, respectively [P = .05]; at 3 months: 0% vs 32% [P = .01]; at
      6 months: 4% vs 36% [P = .01]; at 1 year: 16% vs 48% [P = .03]). CONCLUSIONS:
      When HF is managed by clinical assessment only, estimated LVEDPs remain high at
      discharge, resulting in early and frequent rehospitalization for HF. Therapy
      guided by estimated LVEDP monitoring optimizes filling pressures and reduces HF
      rehospitalization rates.

PMID- 21872141
TI  - Hemodynamic monitoring to guide treatment of acute heart failure.

PMID- 21872139
TI  - Subgroup analysis of a randomized controlled trial evaluating the safety and
      efficacy of cardiac contractility modulation in advanced heart failure.
AB  - BACKGROUND: Cardiac contractility modulation (CCM) signals are nonexcitatory
      electrical signals delivered during the absolute refractory period intended to
      improve contraction. We previously tested the safety and efficacy of CCM in 428
      NYHA functional class III/IV heart failure patients with EF <=35% and narrow QRS
      randomized to optimal medical treatment (OMT) plus CCM (n = 215) versus OMT alone
      (n = 213) and found no significant effect on ventilatory anaerobic threshold
      (VAT), the study's primary end point. In the present analysis, we sought to
      identify if there was a subgroup of patients who showed a response to CCM.
      METHODS AND RESULTS: The protocol specified that multiregression analysis would
      be used to determine if baseline EF, NYHA functional class, pVO(2), or etiology
      of heart failure influenced the impact of CCM on AT. Etiology and baseline pVO(2)
      did not affect efficacy. However, baseline NYHA functional class III and EF >=25%
      were significant predictors of increased efficacy. In this subgroup (comprising
      97 OMT and 109 CCM patients, ~48% of the entire population) VAT increased by 0.10
      +/- 2.36 in CCM versus -0.54 +/- 1.83 mL kg(-1) min(-1) in OMT (P = .03) and
      pVO(2) increased by 0.34 +/- 3.11 in CCM versus -0.97 +/- 2.31 (P = .001) at 24
      weeks compared with baseline; 44% of CCM versus 23% of OMT subjects showed
      improvement of >=1 class in NYHA functional class (P = .002), and 59% of CCM
      versus 42% of OMT subjects showed a >=10-point reduction in Minnesota Living with
      Heart Failure Questionnaire (P = .01). All of these findings were similar to
      those seen at 50 weeks. CONCLUSIONS: The results of this retrospective hypothesis
      generating analysis indicate that CCM significantly improves objective parameters
      of exercise tolerance in a subgroup of patients characterized by normal QRS
      duration, NYHA functional class III symptoms, and EF >25%.

PMID- 21872142
TI  - Clinical utility of three B-type natriuretic peptide assays for the initial
      diagnostic assessment of new slow-onset heart failure.
AB  - BACKGROUND: In patients suspected of new slow-onset heart failure, data on the
      comparative diagnostic performance of automated B-type natriuretic peptide (BNP)
      assays are scarce. METHODS AND RESULTS: Two hundred patients referred to a heart
      failure outpatient diagnostic facility underwent standard diagnostic work-up
      including echocardiography. The reference standard for the diagnosis of heart
      failure was an expert panel conclusion. N-terminal pro-BNP on Elecsys and BNP on
      Axsym and Centaur machines were measured in a single batch. Data were available
      for 172 patients; 51 had heart failure (29.7%). All 3 tests had high c-statistic
      values. An intermediate-risk subset of 111 patients (34% with heart failure) was
      created by excluding patients with very high or very low probability based on
      history and physical examination, the subgroup most in need of an additional
      test. Applying different thresholds for ruling heart failure in or out, the
      positive predicted values in this "gray zone" group were 75%, 76%, and 72%,
      respectively, and the negative predictive values 83%, 71%, and 85%, with the
      remaining 50% of patients having ~18% probability of heart failure. CONCLUSION:
      In practice, a valid diagnosis in patients suspected of slow-onset heart failure
      remains elusive for many in the absence of echocardiographic imaging.

PMID- 21872143
TI  - Short-term variability of heart rate turbulence in chronic heart failure.
AB  - BACKGROUND: Heart rate turbulence (HRT) is associated with risk in chronic heart
      failure (CHF). The objective of this study was to assess the short-term
      variability of HRT and to compare the diagnostic yield of 7-day (7DH) versus 24
      hour (1DH) Holter monitoring for calculating HRT in a CHF population. METHODS AND
      RESULTS: Forty-nine consecutive patients with CHF were studied. At inclusion, 7DH
      was performed to evaluate the variability of HRT parameters. For categorized
      analyses, turbulence onset (TO) >=0% and turbulence slope (TS) <=2.5 ms/RR were
      defined as abnormal, and patients were classified into subgroups based on the
      number of abnormal HRT parameters.The cumulative percentage of patients with
      calculable HRT increased from 69.4% with 1DH to 93.9% with 7DH. The intraclass
      correlation coefficients across the 7-day monitoring were 0.81 (95% confidence
      interval [CI] 0.70-0.89) for TO and 0.90 (95% CI 0.84-0.95) for TS. When
      comparing 2 randomly selected days, TO and TS values were similar (P > .1) and
      showed a strong correlation (TO: r = 0.79; TS: r = 0.84: P < .001). Bland-Altman
      plots showed a mean difference of 0.31% (95% CI -0.07 to 0.70) for TO and 0.44
      ms/RR (95% CI -1.37 to 0.48) for TS. In contrast, categorized analyses showed
      that up to 16% of patients changed their HRT subgroup score from day 1 to day 2
      of comparison. CONCLUSIONS: In this population, 7DH significantly increased the
      percentage of patients with calculable HRT parameters. The short-term variability
      of the quantitative HRT values was good, but when patients were categorized into
      the established HRT subgroups, the concordance was suboptimal.

PMID- 21872144
TI  - Association between prehospital time interval and short-term outcome in acute
      heart failure patients.
AB  - BACKGROUND: Acute heart failure (AHF) is one of the most frequently encountered
      cardiovascular conditions that can seriously affect the patient's prognosis.
      However, the importance of early triage and treatment initiation in the setting
      of AHF has not been recognized. METHODS AND RESULTS: The Tokyo Cardiac Care Unit
      Network Database prospectively collected information of emergency admissions to
      acute cardiac care facilities in 2005-2007 from 67 participating hospitals in the
      Tokyo metropolitan area. We analyzed records of 1,218 AHF patients transported to
      medical centers via emergency medical services (EMS). AHF was defined as rapid
      onset or change in the signs and symptoms of heart failure, resulting in the need
      for urgent therapy. Patients with acute coronary syndrome were excluded from this
      analysis. Logistic regression analysis was performed to calculate the risk
      adjusted in-hospital mortality. A majority of the patients were elderly (76.1 +/-
      11.5 years old) and male (54.1%). The overall in-hospital mortality rate was
      6.0%. The median time interval between symptom onset and EMS arrival (response
      time) was 64 minutes (interquartile range [IQR] 26-205 minutes), and that between
      EMS arrival and ER arrival (transportation time) was 27 minutes (IQR 9-78
      minutes). The risk-adjusted mortality increased with transportation time, but did
      not correlate with the response time. Those who took >45 minutes to arrive at the
      medical centers were at a higher risk for in-hospital mortality (odds ratio 2.24,
      95% confidence interval 1.17-4.31; P = .015). CONCLUSIONS: Transportation time
      correlated with risk-adjusted mortality, and steps should be taken to reduce the
      EMS transfer time to improve the outcome in AHF patients.

PMID- 21872145
TI  - Effects of sertraline on circulating markers of oxidative stress in depressed
      patients with chronic heart failure: a pilot study.
AB  - BACKGROUND: Depression is a common comorbid condition in patients with chronic
      heart failure (CHF). This pilot study investigated the plasma levels of oxidative
      stress markers in depressed CHF patients as well as the effects of antidepressant
      treatment with sertraline on these markers in the same patient population.
      METHODS AND RESULTS: Patients with positive depression screening [Beck Depression
      Inventory (BDI) score >10 and/or Zung Self-Rating Depression Scale >40] underwent
      a psychiatric interview. Patients newly diagnosed as depressed received
      pharmacologic treatment with sertraline for 3 months (arm A) and were compared
      with those who did not comply with the antidepressant treatment (arm B). Markers
      of oxidative stress [malondialdehyde (MDA) and protein carbonyls (PC)], and
      nitrosative stress [nitrotyrosine (NT)] were assessed at baseline and 3 months
      later. Fifty-two out of 254 screened hospitalized CHF patients were diagnosed as
      depressed. Depressed patients had significantly higher levels of MDA compared
      with age- and gender-matched nondepressed patients (n = 40; 3.2 +/- 2.0 vs 2.8 +/
      3.8 MUmol/L; P = .02). Twenty-eight patients received sertraline (arm A), and 24
      refused to receive antidepressant treatment on the top of optimal heart failure
      treatment (arm B). Although baseline levels of MDA and PC in arm A and arm B did
      not differ significantly (P > .05), arm A patients demonstrated a significant
      reduction in MDA (F = 4.657; P = .037) and arm B patients demonstrated no change
      after 3 months. Regarding the examined scores, arm A patients had a decrease in
      BDI score (28 +/- 11 vs 21 +/- 13; P = .008), and arm B patients had no change in
      BDI score at follow-up (P > .05). Arm A had an increase in 6-minute walking
      distance (291 +/- 110 vs 361 +/- 87 m; P = .02), and arm B experienced no change
      (P > .05). CONCLUSIONS: Increased oxidative stress may play a critical role in
      the pathophysiology of depression in CHF. Treatment with sertraline improves
      depressive symptoms and reduces plasma markers of oxidative stress in depressed
      CHF patients.

PMID- 21872146
TI  - Depressive symptom trajectory predicts 1-year health-related quality of life in
      patients with heart failure.
AB  - BACKGROUND: One-third of patients with heart failure (HF) experience depressive
      symptoms that adversely affect health-related quality of life (HRQOL). We aimed
      to describe depressive symptom trajectory and determine whether a change in
      depressive symptoms predicts subsequent HRQOL. METHODS AND RESULTS: The sample
      consisted of 256 inpatients and outpatients with HF. Depressive symptoms were
      measured at baseline and 3 or 6 months with the Patient Health Questionnaire (PHQ
      9). The Minnesota Living with HF Questionnaire was used to assess HRQOL at
      baseline, 3 to 6 months, and 1 year. Based on baseline and 3- to 6-month PHQ-9
      scores, patients were categorized as depressive symptom-free (64%), depressive
      symptoms improved (15%), depressive symptoms developed (6%), or persistent
      depressive symptoms (15%). The groups differed in 1-year HRQOL levels (F = 36, P
      < .001); patients who were depressive symptom-free or whose depressive symptoms
      improved had better 1-year HRQOL than patients with persistent depressive
      symptoms (Tukey honestly significant difference, P < .01). Change in depressive
      symptoms was the strongest predictor of 1-year HRQOL (standardized beta = .42, P
      < .001), after controlling for functional status, demographics, and clinical
      variables. CONCLUSIONS: We found the trajectory of depressive symptoms predicts
      future HRQOL. Research is needed to determine whether interventions targeting
      depressive symptoms improve HRQOL in patients with HF.

PMID- 21872147
TI  - Risk factors for onset of disability among older persons newly diagnosed with
      heart failure: the Cardiovascular Health Study.
AB  - BACKGROUND: As the heart failure population continues to age, disability is
      becoming an increasingly important issue. Our objective was to identify risk
      factors for the onset of disability in activities of daily living among older
      persons with heart failure. METHODS: The study population included participants
      with newly diagnosed heart failure from the Cardiovascular Health Study, a
      longitudinal study of community-living, older persons. Data were collected
      through annual examinations. Cox regression modeling was used to examine
      associations between time-dependent predictors and onset of disability. RESULTS:
      Of 461 participants newly diagnosed with heart failure (mean age 78.7 [SD 5.89]),
      23% subsequently developed disability. The first year after heart failure
      diagnosis was the period of greatest risk for onset of disability (chi-square P
      value <.001). Factors that were independently associated with disability
      included: impaired gait speed (HR 2.29, 95% CI 1.34-3.90); impaired cognition (HR
      1.87, 95% CI 1.14-3.05); and depressive symptoms (HR 1.72, 95% CI 1.04-2.83).
      CONCLUSIONS: Onset of disability is a common occurrence among older persons newly
      diagnosed with heart failure. Risk factors for onset of disability in this
      population are potentially modifiable, and should be routinely assessed in an
      effort to reduce disability in this growing population.

PMID- 21872148
TI  - Isolated noncompaction of the left ventricular myocardium in adults: a systematic
      overview.
AB  - BACKGROUND: Owing to inconsistent diagnostic criteria and small heterogeneous
      cohorts, little is known about the long-term outcomes of adult left ventricular
      noncompaction (LVNC), a rare cardiomyopathy with potentially serious outcomes.
      This systematic overview aimed to better delineate the natural history of adult
      LVNC. METHOD AND RESULTS: A comprehensive computerized search using
      "noncompaction" and its synonyms initially identified 206 articles, with
      reference lists subsequently hand scanned. These searches yielded 5 studies that
      were eligible for this systematic overview, identifying adult cohorts with
      isolated LVNC diagnosed by similar echocardiographic criteria. This combined
      cohort (n = 241) was followed for a mean duration of 39 months. The annualized
      event rate was 4% for cardiovascular deaths, 6.2% for cardiovascular death and
      its surrogates (heart transplantation and appropriate implantable cardioverter
      defibrillator shocks), and 8.6% for all cardiovascular events (death, stroke,
      implantable cardioverter-defibrillator shocks, and heart transplantation.)
      Familial occurrence of LVNC in first-degree relatives was identified by
      echocardiography in 30% of index cases who were screened. CONCLUSION: LVNC is an
      increasingly recognized cardiomyopathy diagnosed by echocardiography and is
      associated with familial tendencies, arrhythmias, thromboembolism, advanced heart
      failure, and death.

PMID- 21872149
TI  - Non-symptom-related factors contributing to delay in seeking medical care by
      patients with heart failure: a narrative review.
AB  - BACKGROUND: Delay in seeking timely medical care by patients with acute coronary
      syndrome and stroke has been well established in the literature, but less is
      known about delay in care-seeking behavior by patients with heart failure (HF).
      The purpose of this narrative review was to synthesize the literature regarding
      non-symptom-related factors that contribute to delay in seeking medical care for
      HF symptoms. METHODS AND RESULTS: A literature search of Scopus, Medline, and
      Pubmed was conducted for published articles from database inception to July 2009.
      Available evidence has shown that non-symptom-related factors, such as HF
      severity, HF history, age, and ethnocultural background, were related to delay in
      certain studies; however, null results have also been reported. Other non-symptom
      related factors, such as male gender, initial contact with a primary care
      physician, arriving in the emergency department by means other than ambulance,
      and patient responses such as self-care, low anxiety, and hopelessness, may play
      a role in longer delay. CONCLUSIONS: Although this review identified several non
      symptom-related factors that may be implicated in care-seeking delay, health care
      professionals should be vigilant in identifying all high-risk individuals and
      educating them about warning signs of HF. Moreover, access to outpatient chronic
      disease management programs that may have potential to reduce care-seeking delay
      behavior should be explored.

PMID- 21872150
TI  - [Bladder reinnervation with creation of a "somato-autonomic" reflex pathway in
      spinal cord injured or spina bifida, a new way for treatment?].
AB  - CONTEXT: The restoration of physiological micturition is a major objective for
      patients presenting a medullary injury, which is not possible with current
      treatment. Several recent studies have purposed some techniques for bladder
      reinnervation. Their purpose was to begin a voluntary micturition by the
      stimulation of an artificial reflex arc created by the anastomosis of a somatic
      root with a root innervating the bladder. MATERIALS AND METHODS: We searched on
      Medline and Cochrane for articles in English. The keywords used were: bladder
      reinnervation, spinal cord injury neurogenic bladder, reflex pathway for
      micturition. RESULTS: These studies reported a variable efficacy as high as 85%
      of the treated patients. These patients could begin micturition voluntarily,
      associated with a significant improvement observed in their postoperative
      urodynamic evaluation. In fact, an improvement of the detrusor external sphincter
      dyssynergia and/or bladder overactivity was reported, and the patients presented
      a better quality of life by the control of their micturition associated with an
      improvement in continence with no need for intermittent catheterisation. However,
      these results were variable from one study to the other, and certain results seem
      difficult to explain notably concerning the abolition of bladder overactivity and
      the improvement of the detrusor external sphincter dyssynergia. CONCLUSION:
      Further experimental studies are still required, notably with animals to confirm
      the encouraging results of these initial studies, and to better understand the
      mechanism before possible routine patient use.

PMID- 21872151
TI  - [Neuro-urology: if you can do the big things, you can do the little things as
      well].

PMID- 21872152
TI  - [Place of sclerotherapy in the treatment of chronic chyluria].
AB  - Chyluria is rare. The parasite that causes filariasis is the most common cause
      while the non-parasitic causes is anecdotal. Medical treatment is often
      insufficient to treat cases of chronic chyluria for which the standard treatment
      is surgical lymphatic disconnection renovascular. However, sclerotherapy by
      instillation of a sclerosing agent kidney may represent an alternative to
      surgery. This technique has the advantage of being less invasive than surgery and
      has a proven efficacy in the literature.

PMID- 21872153
TI  - [Preventive and emergency embolization of angiomyolipomas: our experience].
AB  - AIM: To present our experience with emergency or programmed embolization of
      angiomyolipomas. PATIENTS AND METHODS: The retrospective study 1999-2000 included
      a total of 20 patients with AML, five of whom had hypothyroidism. Group I
      emergency embolization: 11 patients age being 61.4 +/- 15.6 years and the size of
      AML 8.2 +/- 2.8 cm presented retroperitoneal hemorrhage from spontaneous rupture.
      Two had a hemorrhagic shock. A transfusion of 3.4 blood units per patient was
      performed for five patients. A clinical and radiological follow-up was done by
      scanning during the first week and in one month. Group II preventive
      embolization: nine patients, with age between 58.3 +/- 15.2 years and tumor size
      5.2 +/- 2.2 cm, all asymptomatic. All successfully received a unilateral
      preventive embolization. A scan was performed one month later. RESULTS: Group I:
      the embolization was effective in 100% of patients. No intraoperative incident
      was reported. After one month, the reduction in tumor volume was 40%. At eight
      months, a patient underwent nephrectomy because of a new fracture, and another a
      second embolization after 14 months. The technical result was maintained in 83%
      of cases after 18 months. Two patients developed HTA after embolization
      controlled by a single treatment, and five had limited renal ischemic sequels.
      Group II: no intraoperative incidents and no postoperatively complications have
      been reported. One month after embolization, the reduction in tumor volume was
      23%. After 24 months, patients remained completely asymptomatic, no spontaneous
      bleeding has been reported, no surgery has been performed, and no HTA has been
      described. Only one re-embolization was done at 20 months (artery duplicity).
      Limited renal ischemic sequels were reported for one patient but no renal
      failure. CONCLUSIONS: The required embolization became the method of choice in
      emergency with excellent results and few complications at distance. Programmed
      embolization effectively prevented the risk of bleeding, without impact on the
      renal function, with a low economic cost compared to hospitalization and
      emergency care. The significance of the observed AML--hypothyroidism association
      in our series requires a confrontation with more important cohorts.

PMID- 21872154
TI  - [Adult renal cancer in Senegal: Current epidemiological, clinical features,
      profile's evolution over the two past decades].
AB  - OBJECTIVE: To study current epidemiological and clinical features of adult renal
      cancer in Senegal and the evolution of these features over the two past decades.
      PATIENTS AND METHODS: We conducted a retrospective ten years study (2000-2009)
      that analyzed all the renal cell cancer in adult admitted in the urology
      department and the pathology department of the university teaching hospital
      Aristide-Le-Dantec (Dakar). The results of this study were compared with those of
      the previous decade. RESULTS: We included 74 cases of renal cell cancer. The
      median age of patients was 49 years (18-72 years). There was a slight female
      predominance (51.3%). Twenty-eight (37.8%) patients presented at least with one
      renal cell cancer risk factor. The median duration of symptoms was 10 months (1
      96 months). The localization of the renal cancer was right in 42 patients (56.7%)
      and left in 32 cases (43.8%). Almost all the tumors were symptomatic. Symptoms
      were dominated by loin pain (87.8%) and abdominal mass (77%). There were only two
      cases (2.7%) of incidental renal cell cancer. The median tumor size was 12 cm
      (2.4-26 cm). The more frequent tumor stages according to the TNM 2002 staging
      system were T2 (39.2%) and T3 (33.7%). Metastases were found in 23 (31%)
      patients. Forty-four patients underwent nephrectomy (43 radical and one partial).
      No adjuvant treatment or metastasectomy were done. The main histological subtype
      of tumors was renal cell carcinoma (47 cases). The mean duration of the follow up
      was 30.5 +/- 33.6 months. Among the 44 patients who underwent nephrectomy, no
      tumor recurrence was found on 35 cases. Tumor recurrence occurred on nine
      patients. The specific mortality rate was 47.3%. Epidemiological and clinical
      features of the adult renal cell cancer in Senegal haven't significantly changed
      over the 20 past years. CONCLUSION: The adult renal cell cancer incidence was low
      in Senegal. Its clinical profile was characterized by a predominance of locally
      advanced and metastatic forms.

PMID- 21872155
TI  - [Narrow band imaging: description of the technique and initial experience with
      upper urinary tract carcinomas].
AB  - PURPOSE: Endoscopic treatment of upper urinary tract carcinomas (UUTC) is
      becoming more and more prevalent compared to non-conservative surgery. Our goal
      was to determine if NBI technology could improve tumour detection. MATERIAL:
      Twenty-seven patients with known or suspected UUTC were prospectively enrolled
      and treated using the Olympus URF-V flexible ureteroscope. We report 13 new cases
      (48%) and 14 known cases as follow up (52%). White light and NBI were
      subsequently performed to examine the upper urinary tract. Visual aspect of the
      lesions could be compared using both types of light. Biopsies were taken for all
      apparent lesions prior to vaporization by Holmium laser. RESULTS: Forty-three
      lesions were detected in 21 patients. Five lesions (14.2%) in four patients were
      detected through NBI light only among the 35 lesions containing UUTC. Two out of
      four of these patients were new cases and would not have been diagnosed with
      white light alone. Three UUTC-treated (8.5%) had extended margins in NBI.
      Thirteen biopsies (26%) were not valid. Altogether, the tumour detection rate
      improved by 22.7% in seven patients (25.9%) by using the NBI method. CONCLUSION:
      Upper urinary tract endoscopy with NBI light is a new technology that improves
      visualization of UUCT and enables diagnosis of lesions non visible in white
      light. This procedure cannot yet be recommended for daily practice and further
      validation of the technique is required.

PMID- 21872156
TI  - [Seminal vesicle biopsies: Interest in the prostate cancer staging before
      radiation therapy or brachytherapy].
AB  - OBJECTIVE: Seminal vesicle biopsies (SVB) in the staging of prostate cancer are
      controversial. Our main objective was to assess their contribution before
      radiation therapy or brachytherapy. Our secondary objective was to compare
      pathologic findings of the SVB to the magnetic resonance imaging's (MRI) results.
      PATIENTS AND METHODS: From 2000 to 2008, 135 men (median age: 70 years) with
      prostate cancer (cT1a to cT3) underwent SVB right and left. The median PSA was 12
      ng/ml. The median Gleason score was 7. Forty-one patients had an endorectal MRI.
      The median follow-up was 47 months. RESULTS: Seminal vesicle involvement was
      found in 10% of patients. In 9.2% of cases, the biopsy was not contributive. The
      risk of invasion was significantly associated with the stage T3, the Gleason
      score up to 7 and the percentage of prostate positive biopsies. A MRI was
      performed in 41 cases: the correlation between MRI and SVB for the invasion of
      seminal vesicle was significant but moderate (kappa=0.38). The complications rate
      of SVB was 10%. CONCLUSION: SVB were a simple and profitable method. They have
      provided supplementary information that could improve the staging and that could
      lead to the make use of an appropriate treatment. This information was comparable
      to the information provided by MRI. Further studies should establish their role
      in relation to MRI and in particular confirm the best specificity of the SVB.

PMID- 21872157
TI  - [Comparative study of periprostatic tissues thickness after retropubic or
      laparoscopic radical prostatectomy].
AB  - OBJECTIVE: Analysing periprostatic tissue (PPT) thickness after retropubic (RP)
      or laparoscopic (LP) prostatectomy. MATERIAL: From January to December 2007, 114
      consecutives prostatectomies were performed in our institution (38 RP, 76 LP).
      Clinical data were prospectively collected in a database. Gardner et al.'s (1988)
      procedure was used for pathological analysis. PPT thickness was measured on
      pathological specimens by a single observer on a single microscope. The observer
      had no knowledge of either clinical data or surgical approach. Four levels were
      chosen (at the base, the proximal part, the distal part, the apex) and 12
      standardized measures were performed on each level, 48 measures: a prostate. We
      compared PPT thickness and surgical margins according to surgical approach and
      clinical data. RESULTS: Comparative analysis confirmed that LP and RP groups were
      similar as far as it concerns preoperative and pathological findings. Positive
      margin rate was also similar in LP and RP groups (4% versus 5.3%; P=0,37).
      Overall PPT thickness was thinner after LP than after RP except at the apex and
      the anterior face. Nevertheless, in the "complete preservation" group, PPT
      thickness was thinner at the apex in the RP group, thinner at the base in the LP
      group. CONCLUSION: Measuring PPT thickness was an original objective and
      reproducible way to compare different techniques and new technologies for radical
      prostatectomy. PPT sparing was different but not better with the laparoscopic
      approach.

PMID- 21872158
TI  - [Radiotherapy influence, about results of the InVance((r)) male sling in men with
      stress urinary incontinence].
AB  - AIMS: To study impact of previous radiotherapy on urodynamic parameters,
      continence and complication rate, after prosthetic implantation with InVance(r)
      device. PATIENTS AND METHODS: We included 106 patients between August 2004 and
      March 2009. We stratified urinary incontinence according to pads daily used, in
      grade I (one to two pads), II (three to four), or III (more than four or condom
      catheter use). We compared one group of 24 patients with previous radiotherapy
      (R) to 82 control patients (T) without one. Follow-up was made at three and six
      postoperative months and then annually. Results were classified into: no leaks,
      improved or failure. RESULTS: Mean follow-up was 14.8 months (median=12.8) in
      group R and 12.4 months (median=8.8) in group T. At three postoperative months,
      continence was achieved in 62.5% patients from group R and in 77% patients in
      group T (P: ns). At 12 months, results on continence were respectively 52.6% in
      group R and 63.2% in group T (P: ns). Six patients were explanted because of an
      infection (5.7%), among which two in group R (8.3%) and four in group T (4.8%).
      Infection was significantly linked to operative time (P: 0.02). CONCLUSION:
      Previous radiotherapy has no impact on urodynamic parameters and continence, on
      short- and mid-term analysis, after implantation of a bone-anchored suburethral
      sling with InVance(r) device, preferentially patients with mild to moderate
      incontinenec urinary.

PMID- 21872159
TI  - [Stress urinary incontinence treatment using Surgimesh(r) Sling, evolution on
      patient quality of life and sexual activity during 12 months follow-up].
AB  - INTRODUCTION: Evaluation of quality of life (QOL) and sexual activity after using
      sub-urethral Surgimesh(r) Sling for female stress urinary incontinence (SUI).
      METHODS: Study with a total duration of 12 months. One hundred and sixty-eight
      patients presenting a SUI underwent surgery for a Surgimesh(r) Sling
      implantation. RESULTS: QOL was significantly improved on the International
      Consultation Continence Questionnaire (ICIQ) scale with an increase of the
      average score from 2.79+/-1.75 to 8.48+/-1.7 at 12 months (P<0.05). The
      percentage of patients undergoing sexual intercourses remains at a high level
      during the study (76.87% versus 78.33%). The number of patients with pain during
      sexual intercourse significantly decreased (15% versus 2.1%). The QOL score is
      significantly better in post-operation conditions (7.84 versus 9.20; P=0.001). In
      terms of continence at 12 months, 75.6% of women declared recovery and 23.53%
      observed improvements. CONCLUSION: SUI correction using Surgimesh(r) Sling
      induces a very significant improvement in patients' QOL and sexual activity.

PMID- 21872160
TI  - [Alert on the predictable accessibility of the fellowship of urology until 2013:
      a study of the AFUF].
AB  - PURPOSE: To evaluate the accessibility of the fellowship for the residents of
      Urology expecting to accomplish their residentship between November 2010 and
      2013. PATIENTS: Between November 2010 and January 2011, all the residents ongoing
      for the residentship of Urology in France were reached by an electronic mailing
      using the AFUF register. A questionnaire reported all the residents expecting to
      accomplish their residentship between November 2010 and 2013, and the number and
      the expected availability of fellow and specialist assistant posts during the
      same period. RESULTS: Our study counted 306 urologists on training (190
      residents, 76 fellows, 30 assistants, 10 on other posts). On November 2010, 56
      residents accomplished their residentship, while 68 and 79 residents expected to
      accomplish their residentship on November 2011 and 2012, respectively. One
      hundred and six posts validated the fellowship of Urology on November 2010 (76
      fellows, 30 assistants), among 54 posts were available. Over the residents
      expecting to accomplish their residentship on November 2011 and 2012, 22 and 54
      residents may not find a fellow post available. CONCLUSION: The number of
      residents expecting to accomplish the residentship of Urology between November
      2010 and 2013 was increasing, showing a greater interest for this speciality and
      a lack of regulation for its accessibility. By reason of a discrepancy of fellow
      and specialist assistant posts, only 67.6 and 31.6% of the residents expecting to
      accomplish their residentship on November 2011 and 2012 may be able to find a
      post available.

PMID- 21872161
TI  - [Functional damages after blunt renal trauma in children].
AB  - PURPOSE: The purpose of this study was to determine the long-term functional
      outcome of renal injuries. METHODS: We retrospectively reviewed the charts of
      patients under 16 sustaining renal trauma and admitted to our department between
      1990 et 2010. There were 66 renal lesions categorized as follows: grade I to III,
      33, grade IV, 28 and grade V, 5. Whatever their initial status, all children were
      followed using ultrasonography or computed tomography. After complete healing,
      data of technetium-99m-dimercaptosuccinic acid nuclear were collected. RESULTS:
      There was no bilateral injury. Thirteen patients proceeded to laparotomy leading
      to nephrectomy in three cases, partial nephrectomy in two others cases. Four
      renovascular injuries required interventional radiologic management. Nine
      urinomas were managed with eight stentings and one percutaneous drainage.
      Percentage of renal function by technetium-99m-dimercaptosuccinic acid nuclear
      scanning concerning 26 patients was analysed. Split percentage of renal function
      was 43.4% (+/-6.2%), 35.7% (+/-5.3%) et 30.3% (+/-12.2%) (mean+/-SD); P=no
      significant, for grade I-III, IV and V, respectively. CONCLUSION: Functional
      outcome after blunt renal trauma appeared influenced by injury grade. Functional
      sequelae existed even with low-grade traumas. In keeping with literature, these
      results justified a close follow-up in which radionuclide study was the essential
      element.

PMID- 21872162
TI  - [Renal extramedullary hematopoiesis].
AB  - Extramedullary hematopoiesis (EMH) refers to the location of hematopoietic
      elements in locations other than the bone marrow medullary space. EMH is an
      uncommonly isolated disease and it usually occurs during chronic hematologic
      disorders due to hematopoiesis hyperstimulation. Reticuloendothelial system is
      the most common site of EMH whereas the kidney is an extremely rare location. EMH
      lesions are frequently asymptomatic, nevertheless hemorrhagic manifestations can
      be observed. Patient history can help for making a diagnosis, which can be
      established by CT scan and/or MRI. Surveillance is recommended for asymptomatic
      cases while local therapies such as low dose radiation or surgery can be used to
      treat bleeding lesions. Systemic therapies using iron supplementation or blood
      transfusion are helpful to avoid disease recurrence. We report a case of
      pyelocaliceal EMH managed with laser vaporization during ureteroscopy procedures.

PMID- 21872163
TI  - [Renal pseudotumoral actinomycosis: a case report].
AB  - We report the case of a 66-year-old man, presenting a right kidney mass with an
      alteration of the clinical status, treated by radical nephrectomy. Pathology
      reported that it was a pseudotumoral form of a bacterial infection:
      actinomycosis. This is an uncommon disease in this location. The authors wonder
      if it is possible to avoid nephrectomy with a preoperative diagnosis, especially
      with renal biopsy. The patient was well doing after 18 months thanks to long
      lasting and effective postoperative antibiotics (Dhanani et al., 2004).

PMID- 21872164
TI  - Advancing evidence based musculoskeletal physical therapy.

PMID- 21872165
TI  - Gastroenterology in a new era of accountability: part 3. Accountable care
      organizations.

PMID- 21872166
TI  - A rare case of nine twisted adnexal torsion successfully resolved by conservative
      laparoscopic detorsion.

PMID- 21872167
TI  - Incidental duplicate ureteral orifice during transobturator tape procedure.

PMID- 21872168
TI  - Improved premenstrual syndrome symptoms after NovaSure endometrial ablation.
AB  - STUDY OBJECTIVE: To evaluate the change in premenstrual syndrome (PMS) symptoms
      in women with heavy periods who underwent endometrial ablation. DESIGN: The study
      used a prospective, single-arm cohort of adult women who were to undergo NovaSure
      endometrial ablation for heavy menses who also reported symptoms of PMS. A brief
      baseline survey was done to evaluate menstrual bleeding and baseline PMS
      symptoms, and two 30-day prospective validated measures of PMS were used. Follow
      up surveys were sent at 4 to 6 months and included both the brief survey
      questions and the validated measures of PMS (Canadian Task Force classification
      II-3). MEASUREMENTS AND MAIN RESULTS: Thirty-six women with heavy periods who
      were to undergo endometrial ablation had PMS symptoms and completed all surveys
      at baseline and follow-up. The mean age was 41.4 years, with a mean body mass
      index of 26.7. Most (27/36, 75%) had failed hormonal management. All measures of
      PMS showed significant improvement after endometrial ablation. Self-rating of PMS
      symptoms on a scale of 0 (none) to 10 (severe) improved from a baseline of 7.4 to
      a follow-up rating of 3.2 (p <.05). The vast majority of women (35/36, 97%)
      reported improvement in PMS after undergoing endometrial ablation. Both validated
      measures of PMS, Daily Symptoms Report and Daily Record of Severity of Symptoms,
      showed statistically significant improvement in PMS symptoms. CONCLUSION: Women
      with heavy menses and associated PMS symptoms who undergo NovaSure endometrial
      ablation showed improvement in PMS symptoms, as well as reduced menstrual
      bleeding.

PMID- 21872169
TI  - Effects of single vaginal incision technique on quality of life in women with
      stress urinary incontinence.
AB  - STUDY OBJECTIVE: To estimate the short-term effects of a minimally invasive
      single vaginal incision technique without passing through the abdomen or groin
      (ContaSure Needleless System) on the quality of life in women with incontinence.
      DESIGN: Prospective cohort study (Canadian Task Force classification II-2).
      SETTING: Tertiary referral urogynecology clinic. PATIENTS: 50 consecutive
      patients with urodynamically proved stress urinary incontinence from October 2008
      to March 2009. INTERVENTIONS: Preoperative and postoperative scores on the short
      forms of the IIQ-7 (Incontinence Impact Questionnaire, UDI-6 (Urinary Distress
      Inventory) PISQ-12 (Pelvic Organ Prolapse/Urinary Incontinence Sexual Function),
      and long form of the P-QOL (Prolapse Quality of Life) were evaluated in 50
      patients with urodynamically proved stress urinary incontinence. Scores were
      compared with postoperative urodynamic findings. MEASUREMENTS AND MAIN RESULTS:
      Mean (SD) follow-up was 433.5 (44.1) days (95% CI, 420.1-445.1). Patients showed
      statistically significant improvement insofar as preoperative and postoperative
      scores on the IIQ-7, P-QOL, and PISQ-12 and the irritative and stress subgroups
      of UDI-6. Obstructive score of UDI-6 worsened, consistent with the findings of
      pressure-flow studies. Postoperatively, 40 patients (80%) were urodynamically
      continent. Eight patients (16%) were still incontinent; however, their quality of
      life scores (IIQ-7 and UDI-6 stress) improved. Two patients (4%) continued to
      experience leakage, with equal or worsened quality-of-life scores. CONCLUSION:
      Early clinical results of the present trial demonstrate that the ContaSure
      Needleless System seems to be capable of improving significantly all aspects of
      quality of life in women with incontinence. To improve the willingness for
      treatment of women with stress incontinence, this minimally invasive technique
      should be encouraged after confirming its efficacy in larger prospective,
      randomized, comparative trials.

PMID- 21872170
TI  - Endoscopic inguinal lymphadenectomy with a novel abdominal approach to vulvar
      cancer: description of technique and surgical outcome.
AB  - STUDY OBJECTIVE: To evaluate the feasibility and surgical outcome of a novel
      technique of endoscopic inguinal lymphadenectomy to treat vulvar cancer. DESIGN:
      Retrospective analysis performed by a single center over 2 years (Canadian Task
      Force classification II-2). SETTING: Major university teaching hospital.
      PATIENTS: The medical records for 17 consecutive patients who underwent
      endoscopic inguinal lymphadenectomy because of invasive vulvar cancer were
      retrospectively reviewed. INTERVENTION: Endoscopic inguinal lymphadenectomy was
      performed using a novel abdominal approach. MEASUREMENTS AND MAIN RESULTS: All
      patients underwent abdominal endoscopic inguinal lymphadenectomy without
      intraoperative complications. Median (range) operative time for the endoscopic
      procedure was 94 minutes, with estimated blood loss of approximately 137 mL (80
      170 mL). A mean (range) of 16 (11-23) nodes were retrieved. In an additional 5
      patients, pelvic node dissection was performed, with retrieval of 6 (3-11) nodes.
      Of the 17 patients, 2 demonstrated vulvar wound necrosis, and 1 exhibited
      lymphorrhea through the drain orifice. No other inguinal wound-related
      complications were observed. Mean postoperative hospital stay was 11 (8-19) days.
      All patients were followed up for more than 13 months, with no recurrence of
      cancer. CONCLUSIONS: Endoscopic inguinal lymph node dissection using this novel
      abdominal approach in patients with vulvar cancer is a safe and feasible
      technique that may diminish the wound-related complications associated with the
      standard open approach.

PMID- 21872171
TI  - Renaissance of surgical recanalization for proximal fallopian tubal occlusion:
      falloposcopic tuboplasty as a promising therapeutic option in tubal infertility.
AB  - STUDY OBJECTIVE: To assess the clinical effectiveness of falloposcopic tuboplasty
      in tubal infertility. DESIGN: Retrospective cohort study (Canadian Task Force
      classification II-3). SETTING: Infertility clinic. PATIENTS: Three hundred forty
      five infertile patients (>=2y) with a diagnosis of proximal tubal occlusion,
      either bilateral or unilateral, between January 2005 and January 2011.
      INTERVENTION: Falloposcopic tuboplasty. MEASUREMENTS AND MAIN RESULTS: Medical
      records for 345 patients with a diagnosis of proximal tubal occlusion were
      reviewed. Of the 345 patients, 304 underwent falloposcopic tuboplasty, with
      successful recanalization achieved in 248 patients (81.6%). Ninety-one of the 304
      patients (29.9%) became pregnant. Of these, 18 patients (19.8%) miscarried, and 4
      (4.4%) had ectopic pregnancies in the recanalized tube. At 1-, 3-, 6-, and 9
      month follow-up, the cumulative probability of conception was 23.1%, 50.6%,
      73.6%, and 82.4%, respectively. Related complications included postsurgical
      infection (0.3%), perforation of the fallopian tube (1.3%), and accidental
      breakage of the catheter (4.9%) or the falloposcope (1.3%). CONCLUSIONS:
      Falloposcopic tuboplasty is safe and effective for treatment of tubal
      infertility. The pregnancy rate after falloposcopic tuboplasty is comparable to
      that after in vitro fertilization, which suggests that it can be an alternative
      to in vitro fertilization in women with tubal infertility.

PMID- 21872172
TI  - The singer, not the song.
AB  - Recently, data have been published on the possible damage to the healthy ovarian
      tissue determined by surgery for the excision of endometriomas. We believe that,
      besides endometriosis in itself, the overall quality of surgery may have a major
      role in determining damage to the ovary. In recent years, surgeons dedicated to
      the treatment of endometriosis have refined the technique of laparoscopic surgery
      for the excision of endometriomas, with particular attention in developing the
      correct plane of cleavage and in the judicious use of electrosurgery. Quality of
      the surgery, and not surgery per se, may be important. Surgery is the gold
      standard treatment for ovarian endometriomas, but it should be performed with
      proper techniques by specifically trained surgeons. It's the singer, not the
      song.

PMID- 21872173
TI  - Intrauterine contraceptive device migration to the lower urinary tract: report of
      2 cases.
AB  - Several instances of migration of intrauterine contraceptive devices (IUDs) into
      the bladder have been reported. Non-contrast-enhanced computed tomography enables
      excellent visualization of the sites of migrated IUDs. Herein are reported 2
      cases of IUDs that migrated to the lower urinary tract. In the first case, the
      IUD migrated to the bladder. The site of the migrated IUD was accurately
      determined using 3-dimensional ultrasound. In the second case, the IUD migrated
      through the bladder to the opening of the urethra. Both cases were managed
      endoscopically, with excellent outcome. Three-dimensional ultrasound is an
      alternative method for localization of the site of a migrated IUD. We present the
      first case of an IUD migrating through the bladder to the opening of the urethra.
      Endoscopic retrieval is feasible and safe in cases with an intravesically
      migrated IUD.

PMID- 21872174
TI  - Successful robotically assisted laparoscopic correction of chronic uterine
      inversion.
AB  - We report a successful robotically assisted repair of a chronic uterine
      inversion. A modified Spinelli technique was used. The patient was discharged
      home after an uncomplicated postoperative course.

PMID- 21872175
TI  - Metastatic lobular breast carcinoma infiltrating a uterine leiomyoma.
AB  - Metastatic breast cancer is rarely identified in a uterine leiomyoma. Herein is
      reported the case of a 53-year-old patient with untreated left-sided breast
      cancer who later manifested abdominal symptoms and metrorrhagia. After
      hysterectomy, pathologic analysis revealed metastatic lobular breast carcinoma
      involving the uterine fundus and a leiomyoma.

PMID- 21872176
TI  - Internal pudendal artery injury during prolapse surgery using nonanchored mesh.
AB  - Herein is presented the case of a patient with stage 2 uterine prolapse treated
      surgically using nonanchored mesh. Complications were internal pudendal artery
      injury and a massive presacral hematoma that formed after surgery. Transcatheter
      arterial embolization was performed immediately, and the bleeding stopped. The
      patient subsequently experienced difficulty micturating and defecating because of
      presacral hematoma compression. Self-micturation and defecation capabilities were
      regained gradually at approximately 1 week after surgery. The hematoma resolved
      completely by 71 days postoperatively. Comprehensive knowledge of pelvic anatomy
      is important when performing surgery to treat prolapse using mesh kits. Removing
      the mesh and prophylactic antibiotic therapy is a means of conservatively
      managing a pelvic hematoma caused by prolapse surgery.

PMID- 21872177
TI  - Uterine preservation and vaginal reconstruction in a patient with congenital
      vaginal agenesis presenting with cyclic menouria.
AB  - Herein we report the case of a patient with primary amenorrhea and cyclic
      menouria. The patient was a 20-year-old woman with primary amenorrhea and
      inability to achieve sexual intercourse. Clinical examination revealed normally
      developed labia majora and minora, clitoris, and external urethral orifice, but
      no vaginal opening. A mature female pubic hair pattern was present, and axillary
      hair development was normal. Breasts were normally developed. Abdominopelvic
      magnetic resonance imaging demonstrated a remnant upper vagina and unicornuate
      uterus filled with fluid, and left-sided renal agenesis. Intraoperatively, a
      congenital vesicouterine fistulous tract was observed. The fistulous tract was
      completely resected. Vaginal reconstruction using a sigmoid colon pedicled flap
      was performed. The proximal part of the neovagina was connected to the remnant
      cervix, and a Foley catheter was left in the uterine cavity for 7 days to prevent
      obstruction. The patient has been menstruating regularly since the operation.
      Menouria might be an early sign of congenital vesicouterine fistula. Resection of
      the fistulous tract with uterine preservation might be considered in patients
      with vaginal agenesis.

PMID- 21872178
TI  - Fomitiporia ellipsoidea has the largest fruiting body among the fungi.
AB  - A giant polypore, Fomitiporia ellipsoidea, was found in Hainan Island in southern
      China. It was 20 y old, and its estimated volume was 409 000-525 000cm(3) and
      weight was 400-500kg. This is the first report of the largest fungal fruiting
      body both in volume and weight.

PMID- 21872180
TI  - Agni's fungi: heat-resistant spores from the Western Ghats, southern India.
AB  - This study concerns the thermotolerance of spores of mesophilic fungi isolated
      from a tropical semi-arid habitat subject to dry season fire in the Western
      Ghats, southern India. Among 25 species of Ascomycota isolated from leaf litter,
      nine were able to grow after incubation in a drying oven for 2h at 100 degrees C;
      the spores of two of these species survived 2h incubation at 110 degrees C, and
      one survived exposure to 115 degrees C for 2h. The range of thermotolerance among
      mesophilic fungi isolated from the leaf litter was surprising: filamentous fungi
      from other habitats, including species that colonize scorched vegetation after
      fires and thermophilic forms occurring in self-heating plant composts, cannot
      survive even brief exposure to such high temperatures. It is possible that the
      exceptional heat resistance of the Indian fungi is related to adaptations to
      surviving fires. Genetic analysis of the physiological mechanisms of heat
      resistance in these fungi offers prospects for future biotechnological
      innovations. The discovery of extreme thermotolerance among common saprotrophs
      shows that this physiological trait may be more widespread than recognized
      previously, adding to concern about the evolution of opportunistic pathogens on a
      warmer planet. The fungi in this study are among the most heat-resistant
      eukaryotes on record and are referred to here as 'Agni's Fungi', after the Hindu
      God of Fire.

PMID- 21872179
TI  - LongSAGE gene-expression profiling of Botrytis cinerea germination suppressed by
      resveratrol, the major grapevine phytoalexin.
AB  - The ascomycetes Botrytis cinerea is one of the most studied necrotrophic
      phytopathogens and one of the main fungal parasites of grapevine. As a defense
      mechanism, grapevine produces a phytoalexin compound, resveratrol, which inhibits
      germination of the fungal conidium before it can penetrate the plant barriers and
      lead to host cell necrotrophy. To elucidate the effect of resveratrol on
      transcriptional regulation in B. cinerea germlings, two LongSAGE (long serial
      analysis of gene expression) libraries were generated in vitro for gene
      expression profiling: 41 428 tags and among them, 15 665 unitags were obtained
      from resveratrol-treated B. cinerea germlings and 41 358 tags, among them, 16 362
      unitags were obtained from non-treated B. cinerea germlings. In-silico analysis
      showed that about half of these unitags match known genes in the complete B.
      cinerea genome sequence. Comparison of unitag frequencies between libraries
      highlighted 110 genes that were transcriptionally regulated in the presence of
      resveratrol: 53 and 57 genes were significantly down- and upregulated,
      respectively. Manual curation of their putative functional categories showed that
      primary metabolism of germinating conidia appears to be markedly affected under
      resveratrol treatment, along with changes in other putative metabolic pathways,
      such as resveratrol detoxification and virulence-effector secretion, in B.
      cinerea germlings. We propose a hypothetical model of cross talk between B.
      cinerea germinating conidia and resveratrol-producing grapevine at the very early
      steps of infection.

PMID- 21872181
TI  - Aneuraceae (Metzgeriales) and tulasnelloid fungi (Basidiomycota): a model for
      early steps in fungal symbiosis.
AB  - A total of 35 population samples of the liverwort genera Aneura (A. pinguis) and
      Riccardia (R. latifrons, R. multifida, and R. palmata) were sampled from diverse
      habitats and geographical provenances in Germany, Austria, and Switzerland. Light
      and transmission electron microscopy were used to characterise the morphological
      features of the associations, and phylogenetic analyses based on internal
      transcribed spacers (ITS) and the D1/D2 regions of the fungal 28S rDNA were used
      to address diversity and phylogenetic relationships. By comparing the cellular
      structures of the plant-fungus interactions, we recognised the following states
      of fungal colonisation within the thalli: fungus-free, epiphytic, intercellular,
      and intracellular. Colonising hyphae showed dolipores with imperforate
      parenthesomes, slime bodies, and multilayered walls. Colonised liverwort cells
      had pleomorphic nuclei and elongated starch-free chloroplasts with distinctive
      grana. Our analyses revealed six phylogenetic groups of tulasnelloid fungi
      associated with liverworts, where major lineages mostly share similar host and/or
      ecological specialisations. The mode of colonisation of the tulasnelloid
      mycobionts in Aneura and Riccardia sharing identical fungal sequences is
      different. Consequently, the mode of colonisation may be host-dependent. Finally,
      our findings demonstrate that Aneuraceae are model organisms for evolutionary
      studies of symbiotic associations between liverworts and fungi.

PMID- 21872182
TI  - Cryphonectria naterciae: a new species in the Cryphonectria-Endothia complex and
      diagnostic molecular markers based on microsatellite-primed PCR.
AB  - In a recent study intended to assess the distribution of Cryphonectria parasitica
      in Portugal, 22 morphologically atypical orange isolates were collected in the
      Midwestern regions. Eleven isolates were recovered from Castanea sativa, in areas
      severely affected by chestnut blight and eleven isolates from Quercus suber in
      areas with cork oak decline. These isolates were compared with known C.
      parasitica and Cryphonectria radicalis isolates using an integrated approach
      comprising morphological and molecular methods. Morphologically the atypical
      isolates were more similar to C. radicalis than to C. parasitica. Phylogenetic
      analyses based on internal transcribed spacer (ITS) and beta-tubulin sequence
      data grouped the isolates in a well-supported clade separate from C. radicalis.
      Combining morphological, cultural, and molecular data Cryphonectria naterciae is
      newly described in the Cryphonectria-Endothia complex. Microsatellite-primed PCR
      fingerprinting with (GACA)(4) primer discriminated between C. naterciae, C.
      radicalis, and C. parasitica.

PMID- 21872183
TI  - Structures of wall heterogalactomannans isolated from three genera of
      entomopathogenic fungi.
AB  - O-linked heterogalactomannans with similar structural features have been purified
      from the fungal walls of the entomopathogenic fungi Lecanicillium muscarium,
      Beauveria bassiana, Beauveriabrongniartii, and Cordyceps sphingum. Their
      composition and structure have been determined using acid hydrolysis, methylation
      analysis, gas-liquid chromatography-mass spectrometry (GC-MS) and Nuclear
      magnetic resonance spectroscopy (NMR). All structures have an alpha-(1->6)
      mannose backbone, but one of the two strains of L. muscarium included in this
      study contained an acidic heterogalactomannan instead of the neutral
      polysaccharide isolated in the rest of the species analyzed. Sequence analysis of
      the internal transcribed spacer (ITS) region of this strain indicated that it
      belongs to the related genus Simplicillium, displaying low identity (83%) with
      the closest Lecanicillium species. This is a new demonstration of the structural
      diversity of fungal wall heteromannans and validates their interest as
      chemotaxonomic markers. The production of a pullulan-like extracellular
      polysaccharide in strain CBS 413.70C of L. muscarium is also reported.

PMID- 21872184
TI  - Water potential affects Coniothyrium minitans growth, germination and parasitism
      of Sclerotinia sclerotiorum sclerotia.
AB  - Water availability is an important environmental factor which has major effects
      on fungal activity. The effects of osmotic (KCl amended agar) and matric
      Polyethylene glycol ((PEG) 8000 amended agar) potentials over the range -0.1 to 
      5.0MPa on mycelial growth and conidial germination of eight isolates of the
      sclerotial parasite Coniothyrium minitans was assessed. The influence of soil
      water potential on the ability of three selected isolates (LU112, LU545, and
      T5R42i) to parasitise sclerotia of the plant pathogen Sclerotinia sclerotiorum
      was determined. For all eight C. minitans isolates, decreasing osmotic and matric
      potentials caused a reduction in mycelial growth and conidial germination.
      Isolates were more sensitive to decreasing matric potential than osmotic
      potential. Across the isolates, growth at an osmotic potential of -5.0MPa was 30
      70% of the growth seen in the control, whereas less than 20% of the control
      growth was seen at the corresponding matric potential. Across all isolates no
      conidial germination was seen at matric potential of -5.0MPa. The C. minitans
      isolates varied in their sensitivity to decreasing water potentials. Mycelial
      growth and conidial germination of three isolates (LU112, Conio, and CH1) were
      more tolerant of low osmotic potential and matric potential with respect to
      mycelial growth. Isolates T5R42i and LU430 were least tolerant. In contrast,
      conidial germination of isolates Conio, LU545, and T5R42i were less sensitive to
      decreasing matric potential. Soil water potential was seen to affect infection
      and viability of sclerotia by the three C. minitans isolates. Isolate LU545
      reduced sclerotial viability over a wider water potential range (-0.01 to 
      1.5MPa) compared with LU112 (-0.01 to -1.0MPa), with isolate T5R42i being
      intermediate. Indigenous soil fungi (Trichoderma spp. and Clonostachys rosea)
      were recovered from sclerotia but did not result in reduction in sclerotial
      viability. The relevance of these results in relation to biocontrol activity of
      C. minitans in soil is discussed.

PMID- 21872185
TI  - Vectors for fluorescent protein tagging in Phytophthora: tools for functional
      genomics and cell biology.
AB  - Fluorescent tagging has become the strategy of choice for examining the
      subcellular localisation of proteins. To develop a versatile community resource
      for this method in oomycetes, plasmids were constructed that allow the expression
      of either of four spectrally distinct proteins [cyan fluorescent protein (CFP),
      green fluorescent protein (GFP), yellow fluorescent protein (YFP), and mCherry],
      alone or fused at their N- or C-termini, to sequences of interest. Equivalent
      sets of plasmids were made using neomycin or hygromycin phosphotransferases
      (nptII, hpt) as selectable markers, to facilitate double-labelling and aid work
      in diverse species. The fluorescent proteins and drug-resistance markers were
      fused to transcriptional regulatory sequences from the oomycete Bremia lactucae,
      which are known to function in diverse oomycetes, although the promoter in the
      fluorescence cassette (ham34) can be replaced easily by a promoter of interest.
      The function of each plasmid was confirmed in Phytophthora infestans. Moreover,
      fusion proteins were generated using targeting sequences for the endoplasmic
      reticulum, Golgi, mitochondria, nuclei, and peroxisomes. Studies of the
      distribution of the fusions in mycelia and sporangia provided insight into
      cellular organisation at different stages of development. This toolbox of vectors
      should advance studies of gene function and cell biology in Phytophthora and
      other oomycetes.

PMID- 21872186
TI  - Validation of RT-qPCR reference genes for in planta expression studies in
      Hemileia vastatrix, the causal agent of coffee leaf rust.
AB  - Hemileia vastatrix is a biotrophic fungus, causing coffee leaf rust in all coffee
      growing countries, leading to serious social and economic problems. Gene
      expression studies may have a key role unravelling the transcriptomics of this
      pathogen during interaction with the plant host. Reverse transcription
      quantitative real-time polymerase chain reaction (RT-qPCR) is currently the
      golden standard for gene expression analysis, although an accurate normalisation
      is essential for adequate conclusions. Reference genes are often used for this
      purpose, but the stability of their expression levels requires validation under
      experimental conditions. Moreover, pathogenic fungi undergo important biomass
      variations along their infection process in planta, which raises the need for an
      adequate method to further normalise the proportion of fungal cDNA in the total
      plant and fungus cDNA pool. In this work, the expression profiles of seven
      reference genes [glyceraldehyde-3-phosphate dehydrogenase (GADPH), elongation
      factor (EF-1), Beta tubulin (beta-tubulin), cytochrome c oxidase subunit III (Cyt
      III), cytochrome b (Cyt b), Hv00099, and 40S ribosomal protein (40S_Rib)] were
      analysed across 28 samples, obtained in vitro (germinated uredospores and
      appressoria) and in planta (post-penetration fungal growth phases). Gene
      stability was assessed using the statistical algorithms incorporated in geNorm
      and NormFinder tools. Cyt b, 40S_Rib, and Hv00099 were the most stable genes for
      the in vitro dataset, while 40S_Rib, GADPH, and Cyt III were the most stable in
      planta. For the combined datasets (in vitro and in planta), 40S_Rib, GADPH, and
      Hv00099 were selected as the most stable. Subsequent expression analysis for a
      gene encoding an alpha subunit of a heterotrimeric G-protein showed that the
      reference genes selected for the combined dataset do not differ significantly
      from those selected specifically for the in vitro and in planta datasets. Our
      study provides tools for correct validation of reference genes in obligate
      biotrophic plant pathogens, as well as the basis for RT-qPCR studies in H.
      vastatrix.

PMID- 21872187
TI  - Genetic analysis of growth, morphology and pathogenicity in the F(1) progeny of
      an interspecific cross between Fusarium circinatum and Fusarium subglutinans.
AB  - Fusarium circinatum and Fusarium subglutinans are two distinct species in the
      Gibberella fujikuroi species complex. A genetic linkage map produced from an
      interspecific cross between these species was used to identify quantitative trait
      loci (QTLs) associated with variation in mycelial growth and morphology of colony
      margins (CMs) in the 94 F(1) progeny. Mycelial growth was assessed by measuring
      culture size at 25 degrees C and 30 degrees C, while CM morphology was
      characterized in the parents and assessed in their F(1) progeny. In order to test
      the pathogenicity of the progeny, Pinus patula seedlings were inoculated and
      lesion lengths were measured after 3weeks. Seven putative QTLs were associated
      with mycelial growth, three for growth at 25 degrees C and four at 30 degrees C.
      One highly significant QTL (P<0.001) was present at both growth temperatures. For
      CM morphology, a QTL was identified at the same position (P<0.001) as the QTL
      responsible for growth at the two temperatures. The putative QTLs accounted for
      45 and 41% of the total mycelial growth variation at 25 degrees C and 30 degrees
      C, respectively, and for 21% of the variation in CM morphology. Only one of the
      94 F(1) progeny was pathogenic on P. patula seedlings. This observation could be
      explained by the genetic constitution of this F(1) isolate, namely that ~96% of
      its genome originated from the F. circinatum parent. This F(1) individual also
      grew significantly faster at 25 degrees C than the F. circinatum parent (P<0.05),
      as well as more rapidly than the average growth for the remaining 93 F(1) progeny
      (P<0.05). However, no association was found between mycelial growth and
      pathogenicity at 25 degrees C. The highly significant QTL associated with growth
      at two temperatures, suggests that this is a principal genomic region involved in
      mycelial growth at both temperatures, and that the same region is also
      responsible for CM morphology.

PMID- 21872188
TI  - Candida argentea sp. nov., a copper and silver resistant yeast species.
AB  - A new yeast species was isolated from the sediment under metal-contaminated
      effluent from a disused metal mine in mid-Wales, UK. BLAST searching with DNA
      sequence amplified from the ribosomal 26S D1/D2 and ITS regions did not reveal a
      close match with any previously described species (>=6 % and 3 % divergence,
      respectively). Phylogenetic analysis indicated that the species was a member of
      the Saccharomycetales, but did not group closely with other established species,
      the nearest relative being Wickerhamia fluorescens although bootstrap support was
      not strong. In addition to its unusual phylogeny, the species also exhibited
      notable physiological and morphological traits. Isolates exhibited unusually high
      resistance to both copper and silver in laboratory assays. These phenotypes
      appeared to be inherent to the species rather than a transient adaptation to the
      metal-enriched site in Wales, as the same phenotypes were observed in an
      identical (according to 26S rDNA sequence) isolate from Sao Domingos, Portugal in
      the Iberian Pyrite Belt. The species exhibited a multipolar budding-type cell
      division but, unusually, accumulated as rod-shaped cells following division on
      solid medium, contrasting with the larger ellipsoidal cells observed in broth.
      This dimorphism could be discerned readily with flow cytometry. The yeast was
      tolerant of hyper osmotic stress and grew in acidic media (pH 3). This new
      species is designated Candida argentea and five independent strains are deposited
      at the National Collection of Yeast Cultures, UK (NCYC 3753(T), 3754, 3755, 3756,
      3757). Because of its unusual morphological variation and metal resistance
      properties, C. argentea may provide opportunities to gain new insights into the
      physiological and genetic bases of these phenotypes. Results illustrate novel
      fungal biodiversity that can occur at polluted sites.

PMID- 21872189
TI  - Modelling the hyphal growth of the wood-decay fungus Physisporinus vitreus.
AB  - The white-rot fungus, Physisporinus vitreus, degrades the membranes of bordered
      pits in tracheids and consequently increases the permeability of wood, which is a
      process that can be used by the wood industry to improve the uptake of wood
      preservatives and environmentally benign wood modification substances to enhance
      the use and sustainability of native conifer wood species. To understand and
      apply this process requires an understanding of how a complex system (fungus
      wood) interacts under defined conditions. We present a three-dimensional fungal
      growth model (FGM) of the hyphal growth of P. vitreus in the heartwood of Norway
      spruce. The model considers hyphae and nutrients as discrete structures and links
      the microscopic interactions between fungus and wood (e.g. degradation rate and
      degree of opening of pits) with macroscopic system properties, such penetration
      depth of the fungus, biomass, and distribution of destroyed pits in early- and
      latewood. Simulations were compared with experimental data. The growth of P.
      vitreus is characterized by a stepwise capture of the substrate and the effect of
      this on wood according to different model parameters is discussed.

PMID- 21872190
TI  - Attention and suppression affect tactile perception in reach-to-grasp movements.
AB  - Reaching with the hand is characterized by a decrease in sensitivity to tactile
      stimuli presented to the moving hand. Here, we investigated whether tactile
      suppression can be canceled by attentional orienting. In a first experiment,
      participants performed a dual-task involving a goal-directed movement paired with
      the speeded detection of a tactile pulse. The pulse was either delivered to the
      moving or stationary hand, during movement preparation, execution, or the post
      movement phase. Furthermore, stimulation was delivered with equal probability to
      either hand, or with a higher probability to either the moving or resting hand.
      The results highlighted faster RTs under conditions of higher probability of
      stimulation delivery to both moving and resting hands, thus indicating an
      attentional effect. For the motor preparation period, RTs were faster only at the
      resting hand under conditions where tactile stimulation was more likely to be
      delivered there. In a second experiment, a non-speeded perceptual task was used
      as a secondary task and tactile discrimination thresholds were recorded. Tactile
      stimulation was delivered concomitantly at both index fingers either in the
      movement preparation period (both before and after the selection of the movement
      effector had taken place), in the motor execution period, or, in a control
      condition, in the time-window of motor execution, but the movement of the hand
      was restrained. In the preparation period, tactile thresholds were comparable for
      the two timings of stimulation delivery; i.e., before and after the selection of
      the movement effector had taken place. These results therefore suggest that
      shortly prior to, and during, the execution of goal-directed movements, a
      combined facilitatory and inhibitory influence acts on tactile perception.

PMID- 21872191
TI  - [Jellyfish sting or tattoo?].

PMID- 21872192
TI  - [Body-hair transplant for cicatricial alopecia].

PMID- 21872193
TI  - Meta-analysis of early versus deferred revascularization for non-ST-segment
      elevation acute coronary syndrome.
AB  - The impact of a coronary revascularization strategy (early or deferred) on
      clinical outcomes of non-ST-segment elevation acute coronary syndrome (NSTE-ACS)
      has not been well established. The goal of this study was to systematically
      review randomized trials comparing early to deferred revascularization for NSTE
      ACS. A systematic literature search of MEDLINE, ISI Web of Science, and Cochrane
      databases was conducted. Two reviewers independently determined the eligibility
      of clinical trials. Five trials with 4,155 patients were included for analysis.
      Meta-analysis showed that early revascularization produced no significant
      differences in the incidence of death (risk ratio [RR] 0.88, p = 0.47), recurrent
      myocardial infarction (RR 0.92, p = 0.58), and repeat revascularization compared
      to a deferred intervention. However, a significant decrease in refractory
      ischemia was observed in the early intervention group (RR 0.47, p <0.01), and the
      procedure also showed a tendency toward decreasing major bleeding events (RR
      0.77, p = 0.08). According to stratification based on intervention era, extent of
      revascularization, and time of revascularization, subgroup analysis did not show
      between-group differences in all-cause mortality, recurrent myocardial
      infarction, and major bleeding events. Also, sensitivity analysis by
      alternatively using a random-effects model did not find any relevant influence on
      overall results in direction and magnitude. In conclusion, meta-analysis
      demonstrated that early coronary revascularization is feasible and safe for
      patients with NSTE-ACS, might markedly decrease the incidence of refractory
      ischemia, and appears to produce less bleeding.

PMID- 21872194
TI  - Prognostic significance of valvuloarterial impedance and left ventricular
      longitudinal function in asymptomatic severe aortic stenosis involving three
      cuspid valves.
AB  - The purpose of the present study was to evaluate the role of left ventricular
      global afterload and various echocardiographic parameters of systolic function in
      a prospective cohort of 52 asymptomatic patients with severe aortic stenosis
      (indexed aortic valve area 0.4 +/- 0.1 cm2/m2) and normal left ventricular
      ejection fraction (61 +/- 5%). Using 2-dimensional speckle tracking
      echocardiography, myocardial strain, rotation, and twist were evaluated. The
      valvuloarterial impedance (Zva) was calculated as a measure of left ventricular
      global afterload. The predefined end points were the occurrence of symptoms
      (dyspnea, angina, syncope), aortic valve replacement, and death. At study entry,
      all patients had decreased longitudinal strain (LS) (-15 +/- 4%) and increased
      circumferential strain (-22 +/- 5%), twist (24 +/- 7 degrees ), and Zva (5.8 +/-
      2 mm Hg/ml/m2). Increased Zva was closely associated with the circumferential
      strain increase (r = 0.59, p = 0.02) and LS decrease (r = -0.56, p = 0.016). In
      contrast, no relation was found between myocardial function and transaortic
      gradients. During follow-up (11 +/- 7.5 months), on univariate Cox regression
      analysis, the predictors of events were the left ventricular ejection fraction (p
      = 0.02), mass index (p = 0.01), LS (p < 0.0001), radial strain (p = 0.04), and
      Zva (p = 0.0002). On multivariate Cox regression analysis, only the global LS (p
      = 0.03) and Zva (p = 0.03) were independently associated with the combined end
      point. Using receiver operating characteristic curve analysis, a LS of <=-18%
      (sensitivity 96%, specificity 73%) and a Zva of >= 4.7 mm Hg/ml/m2 (sensitivity
      100%, specificity 91%) were identified as the best cutoff values to be associated
      with events. In conclusion, in asymptomatic patients with severe aortic stenosis,
      the degree of global afterload and its consequences on longitudinal function
      might play a role in clinical practice.

PMID- 21872195
TI  - Histopathologic validation of the intravascular ultrasound diagnosis of calcified
      coronary artery nodules.
AB  - A calcified nodule is a type of potentially vulnerable plaque accounting for
      approximately 2% to 7% of coronary events. Because its intravascular ultrasound
      (IVUS) features have never been validated, the aim of this study was to assess
      the IVUS characteristics of calcified nodules in comparison to histopathology.
      IVUS was performed in 856 pathologic slices in 29 coronary arteries (11 left
      anterior descending, 5 left circumflex, and 13 right coronary arteries) in 18
      autopsy hearts. Pathologic sections were analyzed every 2 mm; qualitative and
      quantitative findings of matched IVUS were analyzed. IVUS detected calcification
      in 285 frames; 17 (6.0%) were calcified nodules, and 268 (94.0%) were non-nodular
      calcium by histopathology. Two calcified nodules (11.8%) were solitary, and 15
      (88.2%) were adjacent to non-nodular calcium. IVUS characteristics of calcified
      nodules were (1) a convex shape of the luminal surface (94.1% in calcified
      nodules vs 9.7% in non-nodular calcium, p <0.001), (2) a convex shape of the
      luminal side of calcium (100% vs 16.0%, p <0.001), (3) an irregular luminal
      surface (64.7% vs 11.6%, p <0.001), and (4) an irregular leading edge of calcium
      (88.2% vs 19.0%, p <0.001). Luminal area at the calcified nodule site was larger
      (6.2 +/- 2.4 vs 4.3 +/- 1.6 mm(2), p <0.001) and plaque burden less (57 +/- 6% vs
      68 +/- 5%, p <0.001) than at the minimum luminal area site. In conclusion,
      calcified nodules have distinct IVUS features (irregular and convex luminal
      surface) permitting their prospective identification in vivo.

PMID- 21872196
TI  - A variant upstream of the CDH13 adiponectin receptor gene and metabolic syndrome
      in Swedes.
AB  - Metabolic syndrome (MetS) constitutes a worldwide epidemic burst accounting for
      billions of cardiovascular disease events and deaths. The genetic basis of MetS
      is largely unknown. The rs11646213 T -> A polymorphism maps at 16q23.3 upstream
      of the CDH13 gene codifying for cadherin-13 (also known as T-cadherin or H
      cadherin), which is considered a vascular adiponectin receptor. This and other
      single-nucleotide polymorphisms have been associated with hypertension and
      adiponectin level in separate studies. The aim of the present study was to
      evaluate the effect of the CDH13 rs11646213 T -> A polymorphism on individual
      components of MetS and on MetS. The polymorphism was genotyped in the
      cardiovascular cohort of the Malmo Diet and Cancer Study (n = 4,942) and
      successively in the Malmo Preventive Project (n = 17,675) cohort at baseline and
      after an average of 23 years of follow-up (reinvestigation). Four different
      definitions of MetS were applied to these cohorts. In the cardiovascular arm,
      CDH13 rs11646213 AA homozygotic women showed a trend toward higher triglycerides
      and lower high-density lipoprotein cholesterol and presented a higher MetS score
      (composite sum of MetS phenotypes). MetS (Adult Treatment Panel III definition)
      was more prevalent in AA homozygotic women compared to T-carriers, a result
      confirmed in the Malmo Preventive Project cohort at baseline and at
      reinvestigation with an increased risk from 19% to 45% in AA homozygotic women.
      In conclusion, the CDH13 rs11646213 T > A polymorphism was consistently
      associated with MetS in Swedish women recruited in 2 large cohorts. In light of
      the role of cadherin-13 as a vascular receptor for adiponectin, our study
      supports the genetic basis for the role of adiponectin in MetS pathogenesis.

PMID- 21872197
TI  - Prognostic value of an abnormal ankle-brachial index in patients receiving drug
      eluting stents.
AB  - Advanced atherosclerotic disease increases the risk of stent thrombosis after
      drug-eluting stent (DES) implantation. We aimed to determine if an abnormal ankle
      brachial index (ABI) value as a surrogate of atherosclerotic disease and vascular
      inflammation provides information on 1-year risk of cardiovascular events after
      DES implantation. A prospective cohort of 1,437 consecutive patients undergoing
      DES implantation from January through April 2008 in 26 Spanish hospitals was
      examined. ABI was calculated by Doppler in a standardized manner. Patients were
      followed to 12 months after the percutaneous coronary intervention to determine
      total and cardiovascular mortality, stroke, nonfatal acute coronary syndrome
      (ACS), and new revascularizations. Association of an abnormal ABI value (i.e., <=
      0.9 or >= 1.4) with outcomes was assessed by conventional logistic regression and
      by propensity-score analysis. Patients with abnormal ABI values (n = 582, 40.5%)
      in general had higher global cardiovascular risk, the reason for DES implantation
      was more often ACS, and had a higher rate of complications during admission
      (heart failure or stroke or major hemorrhage 11.3% vs 5.3%, p <0.001). An
      abnormal ABI value was independently associated with 1-year total mortality (odds
      ratio 2.23, 95% confidence interval 1.13 to 4.4) and cardiovascular mortality
      (odds ratio 2.06, 95% confidence interval 1.04 to 4.22). No independent
      association was found between an abnormal ABI value and 1-year nonfatal ACS,
      stroke, and new revascularizations. In conclusion, although an abnormal ABI value
      was associated with fatal outcomes in patients receiving DESs, no association was
      found with nonfatal ACS and new revascularizations. A clear relation between
      abnormal ABI and surrogates of DES thrombosis could not be established.

PMID- 21872198
TI  - Comparison of platelet reactivity and clopidogrel response in patients <= 75
      Years Versus > 75 years undergoing percutaneous coronary intervention for non-ST
      segment elevation acute coronary syndrome.
AB  - Specific data about the clopidogrel response in elderly patients are lacking. The
      present study was performed to compare the platelet reactivity and clopidogrel
      response between patients aged > 75 years and < 75 years undergoing percutaneous
      coronary intervention for non-ST-segment elevation acute coronary syndrome. A
      total of 689 patients were enrolled, including 162 patients aged > 75 years and
      527 younger patients. All patients received a loading dose of 600 mg clopidogrel
      followed by 150 mg/day. Post-treatment platelet reactivity was assessed by
      adenosine diphosphate 10 MUmol/L-induced platelet aggregation and the specific
      pharmacologic response to clopidogrel by the platelet reactivity index vasoactive
      stimulated phosphoprotein. High post-treatment platelet reactivity was defined as
      adenosine diphosphate 10 MUmol/L-induced platelet aggregation >70%. Clinical
      events were recorded during 1 month of follow-up. The patients > 75 years old had
      a greater rate of both ischemic and bleeding complications (p = 0.04 and p =
      0.03, respectively). The post-treatment platelet reactivity in response to both
      the loading and the maintenance clopidogrel dose was greater in patients > 75
      years old than in the younger patients: 50 +/- 17% versus 45 +/- 17% (p = 0.002)
      and 57 +/- 15% versus 53 +/- 16% (p = 0.0005), respectively. The rate of high
      post-treatment platelet reactivity was significantly greater in patients aged >
      75 years after 600 mg and 150 mg clopidogrel: 14% versus 9% (p = 0.04) and 23%
      versus 15% (p = 0.02), respectively. In contrast, the pharmacologic response to
      clopidogrel was not impaired in patients > 75 years after loading and maintenance
      doses: 43 +/- 21% versus 46 +/- 21% (p = 0.17) and 38 +/- 18% versus 39 +/- 18%
      (p = 0.55), respectively. In conclusion, patients aged > 75 years have an
      impaired prognosis after acute coronary syndrome. They display greater post
      treatment platelet reactivity. However, this greater platelet reactivity does not
      seem to be related to an impaired specific response to clopidogrel.

PMID- 21872199
TI  - Intraperitoneal temperature and desiccation during endoscopic surgery.
      Intraoperative humidification and cooling of the peritoneal cavity can reduce
      adhesions.
AB  - This study was conducted to document quantitatively the intraperitoneal
      temperature and desiccation during laparoscopic surgery. The temperature,
      relative humidity, and flow rate were measured in vitro and during laparoscopic
      surgery, at the entrance and at the exit of the abdomen. This permitted us to
      calculate desiccation for various flow rates using either dry CO(2) or CO(2)
      humidified with 100% relative humidity at any preset temperature between 25 and
      37 degrees C. The study showed that desiccation, both in vitro and in vivo,
      varies as expected with the flow rates and relative humidity while
      intraperitoneal temperature varies mainly with desiccation. Temperature
      regulation of bowels is specific and drops to the intraperitoneal temperature
      without affecting core body temperature. With a modified humidifier, desiccation
      could be eliminated while maintaining the intraperitoneal temperature between 31
      to 32 degrees C.

PMID- 21872200
TI  - Gynecologic conditions in participants in the NSABP breast cancer prevention
      study of tamoxifen and raloxifene (STAR).
AB  - OBJECTIVE: This study reports the gynecologic conditions in postmenopausal women
      (intact uterus on enrollment) in the National Surgical Adjuvant Breast and Bowel
      Project (NSABP) study of tamoxifen and raloxifene (STAR)/P-2 trial. STUDY DESIGN:
      This study, with a median follow-up period of 81 months, evaluated the incidence
      rates/risks of gynecologic conditions among women who were treated with tamoxifen
      and raloxifene. RESULTS: Compared with women who received tamoxifen therapy,
      women who received raloxifene therapy had a lower incidence of uterine cancer
      (relative risk, 0.55)/endometrial hyperplasia (relative risk, 0.19), leiomyomas
      (relative risk, 0.55), ovarian cysts (relative risk, 0.60), and endometrial
      polyps (relative risk, 0.30) and had fewer procedures performed. Women receiving
      tamoxifen therapy had more hot flashes (P < .0001), vaginal discharge (P <
      .0001), and vaginal bleeding (P < .0001). CONCLUSION: Our results suggest that
      tamoxifen has more of an estrogenic effect on the gynecologic reproductive
      organs. These effects should be considered in counseling women on options for
      breast cancer prevention.

PMID- 21872201
TI  - Is the treatment of CIN 2 always necessary in women under 25 years old?
AB  - OBJECTIVE: The purpose of this study was to review the outcome of conservatively
      managed cervical intraepithelial neoplasia (CIN) 2 in women <25 years old. STUDY
      DESIGN: This was a retrospective review that included women who were <25 years
      old with biopsy proven CIN2 between 2005 and 2009. Analysis was performed that
      compared women who had immediate treatment with women whose treatment was
      deferred >4 months. The primary outcome measure was spontaneous regression of
      CIN2. Secondary outcomes were treatment rates and loss to follow-up evaluation.
      RESULTS: Of the 452 women who were identified, 256 women (57%) received immediate
      treatment; 157 women (35%) met the definition for conservative management, and 39
      women (9%) had unknown subsequent management. Of the 157 women who were managed
      conservatively, 98 women (62%) showed spontaneous regression, with a median of 8
      months observation. No conservatively managed women progressed to cancer.
      CONCLUSION: Based on the 62% regression rate in this study, routine treatment may
      not be necessary for all women with CIN2 who are <25 years old.

PMID- 21872202
TI  - Clinical features of congenital retinal folds.
AB  - PURPOSE: To investigate the clinical features and prognosis of congenital retinal
      folds without systemic associations. DESIGN: Retrospective observational case
      series. METHODS: The characteristics, clinical course, ocular complications, and
      best-corrected visual acuity (BCVA) of eyes with congenital retinal folds were
      studied during the follow-up periods. The affected and fellow eyes were examined
      by slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and fundus
      fluorescein angiography. The parents and siblings of each patient also underwent
      ophthalmoscopic examinations. The BCVA was measured using a Landolt ring VA
      chart. RESULTS: One hundred forty-seven eyes of 121 patients with congenital
      retinal folds were examined. Fifty-five patients (45.5%) were female. The fold
      was unilateral in 95 patients (78.5%), and 69 of those patients (72.6%) had
      retinal abnormalities in the fellow eye. The meridional distribution of folds was
      temporal in 136 eyes (92.5%). The family history was positive in 32 patients
      (26.4%). Secondary fundus complications, including fibrovascular proliferation
      and tractional, rhegmatogenous, and exudative retinal detachments, developed in
      44 eyes (29.9%). The BCVAs could be measured in 119 eyes and ranged from 20/100
      to 20/20 in 5 eyes (4.2%), 2/100 to 20/200 in 45 eyes (37.8%), and 2/200 or worse
      in 69 eyes (58.0%). The follow-up periods ranged from 4 to 243 months (mean, 79.7
      +/- 58.9 months). CONCLUSIONS: These clinical features suggested that most
      congenital retinal folds may result from insufficient retinal vascular
      development, as in familial exudative vitreoretinopathy, rather than persistent
      fetal vasculature. Adequate management of active retinopathy and late-onset
      complications, especially retinal detachment, is required.

PMID- 21872203
TI  - Ocular surface disease and quality of life in patients with glaucoma.
AB  - PURPOSE: To investigate the relationship between ocular surface disease and
      glaucoma-related quality of life (QoL), glaucoma severity, and treatment in
      patients with open-angle glaucoma. DESIGN: Cross-sectional study. METHODS: 
      SETTING: Clinical practice. STUDY POPULATION: One hundred twenty-four
      participants-patients with mild (n = 48), moderate (n = 34), or severe (n = 19)
      glaucoma and 23 controls (glaucoma suspects) not receiving glaucoma treatment
      were enrolled. Severity was stratified according to binocular visual field loss.
      OBSERVED PROCEDURES: Demographic information, the Ocular Surface Disease Index
      (OSDI), and Glaucoma Quality of Life-15 (GQL-15) questionnaires were
      administered. MAIN OUTCOME MEASURES: OSDI score, GQL-15 score, number and type of
      glaucoma medications, daily dose of benzalkonium chloride (BAK), and visual field
      indices. RESULTS: OSDI scores and the number of patients with OSD increased with
      increasing glaucoma severity (P < .001 and P < .005). GQL-15 scores reflected
      decreased QoL with increasing glaucoma severity (P < .001). These trends were
      maintained after sub-stratification for age and sex. On univariate regression
      OSDI was significantly correlated with GQL-15 summary score, glaucoma severity,
      multiple topical glaucoma medications, worse eye mean deviation and pattern
      standard deviation, use of topical beta blockers, topical carbonic anhydrase
      inhibitors, daily dose of BAK, and glaucoma filtration surgery. On multivariate
      regression GQL-15 summary score (odds ratio [OR] 4.14, 95% confidence interval
      [CI] 2.59-6.63, P < .001) and a daily dose of BAK greater than 3 (OR 2.47, 95% CI
      1.17-5.21, P = .018) were predictive of OSDI score. CONCLUSIONS: OSD is more
      common in patients with increasing glaucoma severity and is associated with
      poorer glaucoma-related QoL and higher exposure to BAK.

PMID- 21872204
TI  - Behcet disease: visual prognosis and factors influencing the development of
      visual loss.
AB  - PURPOSE: To assess the visual prognosis of patients with ocular Behcet disease
      and to determine factors predictive of visual loss and severe visual loss.
      DESIGN: Retrospective case series. METHODS: One hundred seventy-five eyes of 107
      patients diagnosed with ocular Behcet disease were included. The main outcome
      measures were visual loss (best-corrected visual acuity, worse than 20/40) and
      severe visual loss (best-corrected visual acuity, 20/200 or worse). RESULTS: The
      mean duration of follow-up was 6.5 years. Presenting visual acuity was worse than
      20/40 in 50% of eyes and 20/200 or worse in 21% of eyes; approximately one third
      of this was reversible with treatment. The most common cause of irreversible
      severe visual loss was ischemic maculopathy. At 10 years, there was a 39% risk of
      visual loss and a 24% risk of severe visual loss, the latter figure being reduced
      to 13% if patients with irreversible visual loss at presentation were excluded.
      After controlling for potentially confounding variables, male sex, unilateral
      disease, and left eye involvement all were statistically significant risk factors
      for severe visual loss at 5 and 10 years. Patients who were treated with biologic
      agents were less likely to have severe visual loss in either eye at both 5 and 10
      years. CONCLUSIONS: Many patients with ocular Behcet disease still have
      irreversible visual loss at presentation. However, the visual prognosis is
      otherwise improved, with a 10-year risk of severe visual loss of 13% in this
      cohort. The use of biologic agents is associated with a lower risk of severe
      visual loss at 5 and 10 years.

PMID- 21872205
TI  - Differences in clinicopathological characteristics of colorectal cancer between
      younger and elderly patients: an analysis of 322 patients from a single
      institution.
AB  - BACKGROUND: The prognosis of patients with colorectal cancer (CRC) of different
      onset ages is controversial. METHODS: Data were obtained from a prospective
      database at Taipei Veterans General Hospital. There were 2,738 newly diagnosed
      patients with CRC from 2001 to 2006. Two extreme age groups, younger (<=40 years)
      and elderly (>=80 years), were analyzed to compare clinicopathologic
      characteristics and prognosis after exclusion of specific cancer syndrome.
      RESULTS: A total of 322 patients were enrolled in this prospective study. The
      younger group consisted of 69 patients with mean age of 33.5 years, and the
      elderly group consisted of 253 patients with mean age of 83.4 years. Younger
      patients had a higher incidence of mucinous cell type (14.5% vs 6.3%, P = .05),
      poorly differentiated adenocarcinoma (26.1% vs 6.3%, P < .001), more advanced
      disease (82.6% vs 41.9%, P < .001), poorer disease-free survival (67.2% vs 79.3%,
      P = .048), and cancer-specific survival (44.1% vs 73.1%, P < .001) than elderly
      patients. CONCLUSIONS: In patients with CRC of younger onset, without relevant
      predisposing risk factors, younger patients have more advanced stages of disease,
      more aggressive histopathologic characteristics, and poorer prognoses compared
      with older patients.

PMID- 21872206
TI  - Major common bile duct injury and risk of litigation: a surgeon's perspective.
AB  - Risk for a lawsuit for medical malpractice has unfortunately become part of
      physicians' daily professional activities, with a blowout in indemnity insurance
      premiums, especially in high-risk medical specialties. Common bile duct injury
      following laparoscopic cholecystectomy is a well-recognized and feared
      complication for surgeons because of its associated morbidity, and it also ranks
      among the leading sources of medical malpractice claims against surgeons in the
      world. The purpose of this article is to raise awareness within the medical
      community and in particular among specialist surgeons on the important threat
      they could be facing in terms of litigation in the event of an adverse surgical
      outcome following such a commonly performed procedure. There is a real need for
      open debate on this concerning topic, as the fear of lawsuits and exorbitant
      malpractice premiums are pushing a substantial number of medical professionals to
      practice defensive medicine, reflected by the avoidance of performing certain
      procedures or treating high-risk patients perceived to have higher litigation
      rates, or simply walking away from their current practices, creating a chronic
      shortage of specialized doctors in certain surgical areas.

PMID- 21872207
TI  - The ribs or not the ribs: which influences mortality?
AB  - BACKGROUND: The relative impact of rib fractures on mortality risk is unclear.
      This study examined the respective relationships between mortality and the number
      of fractured ribs, patient age, and severity of intrathoracic and extrathoracic
      injuries. METHODS: The National Trauma Data Bank was queried, abstracting
      mortality, age, number of ribs fractured, associated intrathoracic and
      extrathoracic injury, and Abbreviated Injury Score codes. RESULTS: Multivariate
      logistic regression indicated the strongest influence on mortality was severity
      of intrathoracic injury, followed by severity of extrathoracic injury, age 65
      years or older, more than 5 ribs fractured, and age 46 to 65 years. The mortality
      rate for isolated rib fractures ranged from 1.8% to 3.2%. CONCLUSIONS: Mortality
      related to rib fractures is affected independently by severe intrathoracic
      injury, presence of extrathoracic injury, advanced age, and more than 5 fractured
      ribs. Patients with these conditions may benefit from a higher level of care.

PMID- 21872208
TI  - Palliative resections versus palliative bypass procedures in pancreatic cancer--a
      systematic review.
AB  - BACKGROUND: Although resection is the only treatment option that offers a chance
      for prolonged survival in pancreatic cancer, R2 resections are controversial and
      not a generally accepted approach. METHODS: A systematic review and meta-analysis
      of studies of patients with pancreatic cancer was performed to analyze R2
      resections in comparison with palliative surgical bypass procedures. Trials were
      identified by searching MEDLINE, Embase, and the Cochrane Central Register of
      Controlled Trials from 1966 to February 2011. RESULTS: Four cohort studies were
      identified comparing 138 patients with R2 resections with 261 patients undergoing
      surgical bypass procedures. Morbidity and mortality were increased in the R2
      resection group, with pooled risk ratios of 1.75 (95% confidence interval [CI],
      1.35-2.26; P < .0001) and 2.98 (95% CI, 1.31-6.75; P = .009), respectively. R2
      resections were associated with longer operating times (mean difference, 164
      minutes; 95% CI, 127-201 minutes; P < .00001) and hospital stays (mean
      difference, 5 days; 95% CI, 1-9 days; P = .02). Pooled median survival times were
      8.2 months for R2 resection and 6.7 months for palliative bypass procedures.
      CONCLUSIONS: Planned palliative R2 resections are not justified in patients with
      pancreatic cancer.

PMID- 21872210
TI  - [Myocardial function analysis with echocardiography-Doppler in septic shock].
AB  - Septic shock is a severe sepsis associated with cardio-circulatory failure and
      tissular hypoperfusion. Echocardiography-Doppler remains essential for the
      assessment of myocardial function in septic shock. This ultrasound procedure
      helps clinicians for the analysis of left ventricular systolic function, left
      ventricular diastolic function, right ventricular function and cardiac filling.

PMID- 21872209
TI  - Costs and quality of life associated with radial artery and saphenous vein
      cardiac bypass surgery: results from a Veterans Affairs multisite trial.
AB  - BACKGROUND: In coronary artery bypass grafting (CABG) surgery, there is
      uncertainty about whether the radial artery affects quality of life or costs
      relative to the saphenous vein. This study compared the cost and quality of life
      for patients randomized to either radial artery or saphenous vein grafts.
      METHODS: We analyzed the duration and cost of the index surgery and costs and
      quality of life (Seattle Angina Questionnaire and Health Utility Index) at 1 year
      for 726 participants. RESULTS: The 2 treatment groups had similar baseline
      characteristics. Using the radial artery added approximately 31 minutes to the
      surgery (from skin incision to skin closure; P < .001) compared with a saphenous
      vein graft. There were no significant differences in terms of costs and quality
      of life after the index hospitalization or at 1 year. CONCLUSIONS: Coronary
      artery bypass grafting with the radial artery lasts approximately 31 minutes
      longer than with the saphenous vein. However, costs and the quality of life were
      not statistically different.

PMID- 21872211
TI  - [Smokeless tobacco and cardiovascular risk].
AB  - The use of "snus" (smokeless tobacco) can be detrimental to health. Snus delivers
      rapidly high doses of nicotine which can lead to addiction. The use of snus
      increases the risk of myocardial infarction and stroke. Nicotine substitution
      therapy as well as bupropion and varenicline reduce withdrawal symptoms and
      tobacco craving during snus cessation. However, they have been shown not to
      assist in long-term abstinence. Information concerning potential cardiovascular
      hazards of snus must be incorporated into health educational programs in order to
      discourage its use. Snus is not a recommended product to help stop smoking.

PMID- 21872212
TI  - Surgical interventions for atrioventricular septal defect subtypes: the pediatric
      heart network experience.
AB  - BACKGROUND: The influence of atrioventricular septal defect (AVSD) subtype on
      outcomes after repair is poorly understood. METHODS: Demographic, procedural, and
      outcome data were obtained 1 and 6 months after AVSD repair in an observational
      study conducted at 7 North American centers. RESULTS: The 215 AVSD patients were
      subtyped as 60 partial, 27 transitional, 120 complete, and 8 with canal-type VSD.
      Preoperatively, transitional patients had the highest prevalence of moderate or
      severe left atrioventricular valve regurgitation (LAVVR, p = 0.01). At repair,
      complete AVSD and canal-type VSD patients, both with the highest prevalence of
      trisomy 21 (p < 0.001), were younger (p < 0.001), had lower weight-for-age z
      scores (p = 0.005), and had more associated cardiac defects (p < 0.001).
      Annuloplasty was similar among subtypes (p = 0.91), with longer duration of
      ventilation and hospitalization for complete AVSD (p < 0.001). Independent
      predictors of moderate or severe LAVVR at the 6-month follow-up were older
      log(age) at repair (p = 0.02) but not annuloplasty, subtype, or center (p > 0.4).
      Weight-for-age z scores improved in all subtypes at the 6-month follow-up, and
      improvement was similar among subtypes (p = 0.17). CONCLUSIONS: AVSD subtype was
      significantly associated with patient characteristics and clinical status before
      repair and influenced age at repair. Significant postoperative LAVVR is the most
      common sequela, with a similar prevalence across centers 6 months after the
      intervention. Annuloplasty failed to decrease the postoperative prevalence of
      moderate or severe LAVVR at 6 months. After accounting for age at repair, AVSD
      subtype was not associated with postoperative LAVVR severity or growth failure at
      6 months. Further investigation is needed to determine if interventional
      strategies specific to AVSD subtype improve surgical outcomes.

PMID- 21872213
TI  - Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm
      outcomes.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used occasionally as a
      bridge to lung transplantation. The impact on mid-term survival is unknown. We
      analyzed outcomes after lung transplant over a 19-year period in patients who
      received ECMO support. METHODS: From March 1991 to October 2010, 1,305 lung
      transplants were performed at our institution. Seventeen patients (1.3%) were
      supported with ECMO before lung transplant. Diagnoses included retransplantation
      (n = 6), pulmonary fibrosis (n = 6), cystic fibrosis (n = 4), and chronic
      obstructive pulmonary disease (n = 1). Fifteen patients underwent double lung
      transplant, one patient had single left lung transplant and one patient had a
      heart-lung transplant. Venovenous and venoarterial ECMO were implanted in eight
      and nine cases, respectively. Median duration of support was 3.2 days (range, 1
      to 49 days). Mean patient follow-up was 2.3 years. RESULTS: Thirty-day, 1-year,
      and 3-year survivals were 81%, 74%, and 65%, respectively, for the supported
      patients and 93%, 78%, and 62% in the control group (p = 0.56). Two-year survival
      was not affected by ECMO type, with survival of five out of nine patients
      supported by venoarterial ECMO vs seven out of eight patients supported by
      venovenous ECMO (p = 0.17). At 1- year follow-up, allograft function for the ECMO
      supported patients did not differ from the control group (forced expiratory
      volume in one second, 2.35 L vs 2.09 L, p = 0.39) (forced vital capacity, 3.06 L
      vs 2.71 L, p = 0.34). CONCLUSIONS: Extracorporeal membrane oxygenation as a
      bridge to lung transplantation is associated with higher perioperative mortality
      but acceptable mid-term survival in carefully selected patients. Late allograft
      function did not differ in patients who received ECMO support before lung
      transplant from those who did not receive ECMO.

PMID- 21872215
TI  - Neurogenetic effects of OXTR rs2254298 in the extended limbic system of healthy
      Caucasian adults.

PMID- 21872214
TI  - Pulmonary artery and conduit reintervention rates after norwood using a right
      ventricle to pulmonary artery conduit.
AB  - BACKGROUND: There is a high incidence of cardiovascular reinterventions in
      patients undergoing a Norwood procedure (NP). The goal of this study was to
      analyze the rate of pulmonary artery (PA) and conduit stenosis using the right
      ventricle (RV)-to-PA modification of the NP. METHODS: Patients who underwent a NP
      January 2005 to December 2009 were included. The procedure was performed with a
      ringed conduit sutured to a membrane to form a patch. The patch was sutured to
      the PA confluence, and the spatulated conduit was anastomosed to an appropriately
      sized right ventriculotomy. Rates of PA and conduit stenosis requiring
      reintervention were calculated based on cardiac catheterization data. RESULTS:
      Thirty-three patients with hypoplastic left heart syndrome underwent a NP.
      Perioperative mortality was 6% (2 of 33). Twenty-eight patients (85%) had a Glenn
      procedure 5 +/- 1 months later, and 12 patients (36%) had a Fontan procedure 34
      +/- 2 months after the Glenn. Pulmonary artery stenosis occurred in 11 patients
      (33%), and RV-PA conduit stenosis occurred only in 2 patients (6%). One-year and
      3-year actuarial survival rates were 82% and 77%, respectively. Both branch PAs
      showed good and symmetric growth at cardiac catheterization before Glenn.
      CONCLUSIONS: The NP with RV-PA conduit using a ringed graft and a pulmonary patch
      is a technique associated with a low rate of PA and conduit stenosis, and good
      outcomes.

PMID- 21872216
TI  - Antidepressant medication use and risk of hyperglycemia and diabetes mellitus: a
      noncausal association?
AB  - BACKGROUND: Previous research suggests a link between antidepressant use and
      diabetes, but it is unclear whether the association is causal or attributable to
      detection/ascertainment bias. To examine this, we assessed the associations of
      antidepressant use with change in glucose levels and incidence of undiagnosed and
      diagnosed diabetes. METHODS: During an 18-year period, we monitored
      antidepressant use, glucose levels, and diabetes status in 5978 civil servants
      (70.9% male, age range 39-64 years) free of diabetes at baseline (the Whitehall
      II study). Use of medication and plasma glucose were assessed at four study
      screenings: 1991/1993, 1997/1999, 2003/2004, and 2008/2009. Incident diabetes
      cases were classified as either diagnosed (n = 294) if detected using self-report
      of physician diagnosis and/or the use of diabetes medication or undiagnosed (n =
      346) if detected based on fasting and/or 2-hour postload glucose levels using an
      oral glucose tolerance test at the study screenings. RESULTS: Incidence of
      diagnosed diabetes was higher among antidepressant users than nonusers (odds
      ratio 3.10, 95% confidence interval: 1.66-5.78). However, antidepressant use was
      not associated with undiagnosed diabetes at any follow-up examination nor with
      higher fasting or 2-hour postload plasma glucose levels or increasing glucose
      levels over time. Odds ratio for undiagnosed diabetes for antidepressant users
      versus nonusers was .88 (95% confidence interval: .45-1.72, p = .70). The mean
      difference in glucose changes between participants reporting antidepressant use
      at three screenings compared with those not on antidepressant treatment was .0
      mmol/L. CONCLUSIONS: The link between antidepressant use and diabetes risk may
      not be causal in nature.

PMID- 21872217
TI  - Decreased dendritic spine density and abnormal spine morphology in Fyn knockout
      mice.
AB  - Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP),
      synapse formation, and learning and memory. Fyn is also implicated in dendritic
      spine formation both in vitro and in vivo. However, whether Fyn's regulation of
      dendritic spine formation is brain-region specific and age-dependent is unknown.
      In the present study, we systematically examined whether Fyn altered dendritic
      spine density and morphology in the cortex and hippocampus and if these effects
      were age-dependent. We found that Fyn knockout mice trended toward a decrease in
      dendritic spine density in cortical layers II/III, but not in the hippocampus, at
      1 month of age. Additionally, Fyn knockout mice had significantly decreased
      dendritic spine density in both the cortex and hippocampus at 3 months and 1
      year, and Fyn's effect on dendritic spine density was age-dependent in the
      hippocampus. Moreover, Fyn knockout mice had wider spines at the three time
      points (1 month, 3 months, 1 year) in the cortex. These findings suggest that Fyn
      regulates dendritic spine number and morphology over time and provide further
      support for Fyn's role in maintaining proper synaptic function in vivo.

PMID- 21872219
TI  - Taltirelin, a thyrotropin-releasing hormone analog, alleviates mechanical
      allodynia through activation of descending monoaminergic neurons in persistent
      inflammatory pain.
AB  - Thyrotropin-releasing hormone (TRH) and its analogs have been reported to
      modulate descending monoaminergic inhibitory neurons, resulting in
      antinociception. However, it remains unknown whether TRH exerts an antiallodynic
      effect during persistent pain. Here, we investigated the action of taltirelin, a
      stable TRH analog, on mechanical allodynia in mice with inflammatory persistent
      pain induced by an injection of complete Freund's adjuvant into the hindpaw.
      Systemic administration of 1.0 mg/kg taltirelin markedly reduced mechanical
      allodynia. This effect was abolished by the 6-hydroxydopamine (6-OHDA)-induced
      depletion of central noradrenaline. While intraperitoneal injection of the alpha1
      adrenoceptor antagonist prazosin had no effect, intraperitoneal and intrathecal
      administration of the alpha2-adrenoceptor antagonist yohimbine prevented the
      antiallodynic action of taltirelin. In addition, DL-p-chlorophenylalanine (PCPA)
      induced depletion of serotonin (5-HT) and intraperitoneal and intrathecal
      injection of the 5-HT(1A) receptor antagonist WAY-100635 blocked the effect of
      taltirelin on allodynia. These findings suggest that taltirelin alleviates
      mechanical allodynia in inflammatory persistent pain by modulating the descending
      noradrenergic and serotonergic neuronal pathways via indirect activation of
      spinal alpha2-adrenergic and 5-HT(1A) receptors.

PMID- 21872218
TI  - Comparison of CRF-immunoreactive neurons distribution in mouse and rat brains and
      selective induction of Fos in rat hypothalamic CRF neurons by abdominal surgery.
AB  - Mice and rats are widely used in stress-related behavioral studies while little
      is known about the distribution of the stress hormone, corticotropin-releasing
      factor (CRF) in the mouse brain. We developed and characterized a novel rat/mouse
      CRF polyclonal antibody (CURE ab 200101) that was used to detect and compare the
      brain distributions of CRF immunoreactivity in naive and colchicine-treated rats
      and mice. We also assessed whether the visceral stressor of abdominal surgery
      activated brain CRF neurons using double labeling of Fos/CRF in naive rats. CRF
      ir neurons were visualized in the cortex, bed nucleus of the stria terminalis,
      central amygdala, hypothalamic paraventricular nucleus (PVN), Barrington's
      nucleus and dorsolateral tegmental area in naive rats. CRF-immunoreactive (ir)
      neurons in the mouse brain were detected only after colchicine. The pattern shows
      fundamental similarity compared to the colchicine-treated rat brain, however,
      there were differences with a lesser distribution in both areas and density
      except in the lateral septum and external subnucleus of the lateral parabrachial
      nucleus which contained more CRF-ir neurons in mice, and CRF-ir neurons in the
      dorsal motor nucleus of the vagus were found only in mice. Abdominal surgery in
      naive rats induced Fos-ir in 30% of total CRF-ir neurons in the PVN compared with
      control (anesthesia alone) while Fos was not co-localized with CRF in other brain
      nuclei. These data indicate that CRF-ir distribution in the brain displays
      similarity as well as distinct features in mice compared to rats that may
      underlie some differential stress responses. Abdominal surgery activates CRF-ir
      neurons selectively in the PVN of rats without colchicine treatment.

PMID- 21872220
TI  - The effects of opioid receptor antagonists on electroacupuncture-produced anti
      allodynia/hyperalgesia in rats with paclitaxel-evoked peripheral neuropathy.
AB  - Research supports the effectiveness of acupuncture for conditions such as chronic
      low back and knee pain. In a five-patient pilot study the modality also improved
      the symptoms of chemotherapy-induced neuropathic pain. Using an established rat
      model of paclitaxel-induced peripheral neuropathy, we evaluated the effect of
      electroacupuncture (EA) on paclitaxel-induced hyperalgesia and allodynia that has
      not been studied in an animal model. We hypothesize that EA would relieve the
      paclitaxel-induced mechanical allodynia and hyperalgesia, which was assessed 30
      min after EA using von Frey filaments. Beginning on day 13, the response
      frequency to von Frey filaments (4-15 g) was significantly increased in
      paclitaxel-injected rats compared to those injected with vehicle. EA at 10 Hz
      significantly (P<0.05) decreased response frequency at 4-15 g compared to sham
      EA; EA at 100 Hz only decreased response frequency at 15 g stimulation. Compared
      to sham EA plus vehicle, EA at 10 Hz plus either a MU, delta, or kappa opioid
      receptor antagonist did not significantly decrease mechanical response frequency,
      indicating that all three antagonists blocked EA inhibition of allodynia and
      hyperalgesia. Since we previously demonstrated that MU and delta but not kappa
      opioid receptors affect EA anti-hyperalgesia in an inflammatory pain model, these
      data show that EA inhibits pain through different opioid receptors under varying
      conditions. Our data indicate that EA at 10 Hz inhibits mechanical
      allodynia/hyperalgesia more potently than does EA at 100 Hz. Thus, EA
      significantly inhibits paclitaxel-induced allodynia/hyperalgesia through spinal
      opioid receptors, and EA may be a useful complementary treatment for neuropathic
      pain patients.

PMID- 21872222
TI  - Rate dependency of vibrotactile stimulus modulation.
AB  - Adaptation has a pronounced impact on the perception of vibrotactile stimuli.
      Previously, we demonstrated that the duration of vibrotactile conditioning was
      directly proportional to the impact that adaptation has on sensory perception
      (Tannan et al., 2007b). Prior reports had proposed that the impact of adaptation
      on the perceived magnitude of vibrotactile stimuli was specific to the
      conditioning amplitude (Goble and Hollins, 1993), and this concept led us to
      hypothesize that if the amplitude of a vibrotactile stimulus was changed
      continuously, that this modulation would itself impact adaptation. In order to
      test this idea, two repetitive vibrotactile stimuli were simultaneously delivered
      to two adjacent finger tips (D2 and D3). In a matching task, a standard stimulus
      was maintained at constant amplitude (defined as "stationary"), while the
      amplitude of the test stimuli was increased at a fixed rate (i.e., 10 MUm/s;
      defined as "non-stationary") from a null value up to the level that a subject
      (n=50) indicated that the two stimuli were perceived to be identical. Changing
      the standard amplitude yielded results consistent with Weber's Law and changing
      the modulation rate yielded results that were consistent with our initial
      hypothesis that faster modulation rates would lead to the non-stationary stimulus
      as being less adapted. A comparative study, using the above-described method, was
      conducted with 12 autism subjects who were previously reported to have below
      normal adaptation metrics (Tannan et al., 2008). The findings of this pilot
      autism study suggest that rate dependent modulation of vibrotactile stimuli could
      provide a more sensitive metric of adaptation, as the observations demonstrate a
      bimodal distribution within the autism spectrum.

PMID- 21872223
TI  - Characterisation of oligosaccharides from the chondroitin/dermatan sulphates:
      (1)H and (13)C NMR studies of oligosaccharides generated by nitrous acid
      depolymerisation.
AB  - The polymers chondroitin sulphate and dermatan sulphate have been fragmented by
      an anhydrous hydrazine/nitrous acid procedure. The resulting disaccharides from
      the polymer repeat sequences were reduced with NaBH(4) and purified by ion
      exchange chromatography. Whereas enzymatic depolymerisation leads to the loss of
      the distinction between glucuronic and iduronic acids of CS and DS in the
      resultant disaccharides, nitrous acid depolymerisation retains these structures.
      Complete (1)H and (13)C NMR data have been derived for the major components which
      were shown to have the structures: GlcA-(beta1->3)-anTal6S-ol (I) and L-IdoA
      (alpha1->3)-anTal4S-ol (II), where anTal-ol represents (2,5)anhydro-D-talitol and
      6S/4S represent O-ester sulphate groups at C-6/C-4 sites.

PMID- 21872221
TI  - The effect of intracerebroventricular infusions of ghrelin and/or short fasting
      on the gene expression and immunoreactivity of somatostatin in the hypothalamic
      neurons and on pituitary growth hormone in prepubertal female lambs.
      Morphological arguments.
AB  - The effect of exogenous ghrelin on somatostatin distribution in the ruminant's
      hypothalamus has not been yet determined. The aim of the present study was to
      investigate the consequence of central infusion of ghrelin and/or short fasting
      on the secretory activity of the somatostatin/GH system in prepubertal female
      sheep. Animals were randomly divided into three groups, two standard fed and one
      fasted for 72 h. One standard group and one fasted group were infused icv with
      vehicle, while the remaining standard group was infused with ghrelin (25 MUl/120
      MUl/h). Infusions were performed for 6 h during three consecutive days; blood
      samples were collected during the "day 0" (before the infusion) and "day 3"
      Immediately after the experiment the sheep were slaughtered. Parts of the brains
      were fixed in situ for further immunohistochemical analysis The remaining brains
      were frozen for RT-PCR analysis. Fasting and ghrelin infusion elicited the same
      kind of changes in the secretory activity of the somatostatin/GH system compared
      to standard fed sheep. The expression of somatostatin mRNA and ir somatostatin in
      the PEV nucleus and ir stores in the median eminence increased in both these
      groups compared to standard fed sheep (P<0.001). The population of ir GH
      pituitary cells decreased (P<0.001), the mean GH plasma concentrations increased
      in all fasted and ghrelin infused animals between day 0 and day 3 of infusions
      (P<0.05) compared to the standard fed group. It can be suggested that ghrelin
      takes part in the mechanisms linking the nutritional status of an organism with
      an activity of the somatotrophic axis on the level of the CNS by stimulating GH
      release through suppression of the somatostatin output.

PMID- 21872224
TI  - Targeting interferon regulatory factors to inhibit activation of the type I IFN
      response: implications for treatment of autoimmune disorders.
AB  - The type I interferon (IFN) response plays a critical role in autoimmunity and is
      induced by innate receptor ligation and activation of IFN-regulatory factors
      (IRF). The present study investigated the roles and functional hierarchy of IRF3,
      IRF5, and IRF7 in expression of cytokines, chemokines, and matrix
      metalloproteinases in human THP1 monocytic cells. Targeted IRF knockdown was
      followed by evaluation of gene expression, promoter activation, and mRNA
      stability to determine the role of IRF as potential targets for modulating IFN
      responses in patients with autoimmune diseases. IRF played a distinct role in
      regulation of type I IFN gene expression in human monocytic cells and
      specifically regulated gene expression through the IFN-stimulated response
      element, with no contribution to transcription of traditionally AP-1 or NF-kB
      regulated genes. IRF7 regulated IL-6 gene expression by increasing IL-6 mRNA
      stability. IRF regulation of inflammation and induction of the IFN signature
      might contribute to the pathogenesis of autoimmune diseases and therefore
      represent novel therapeutic targets.

PMID- 21872225
TI  - Anti-IFN autoantibodies are present in healthy Egyptian blood donors at low
      titer.
AB  - Autoantibody against interferon is associated in many viral and non-viral
      diseases. This study aimed to determine the prevalence of anti-IFN-alpha
      autoantibodies in healthy Egyptian blood donors. The study included 558 (100
      females (17.92%) and 458 males (82.08%)) Egyptian healthy blood donors who showed
      normal levels of liver enzymes and kidney tests and were conformed negative for
      hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs),
      HIV-1/2 Abs, anti-HBc and Treponema Abs. Autoantibody against IFN-alpha-1a and
      IFN-alpha-2b were screened using ELISA. Anti-IFN-alpha-1a positive cases were
      found to be 43 subject (7.76%; 6 females (1.08%); 37 males (6.68%)) and anti-IFN
      alpha-2b positive cases were found to be 3 (0.54%; all males). Combined
      positivity against both IFN-alpha-1a and IFN-alpha-2b was 38 (6.86%; 7 females
      (1.26%) and 31 males (6.60%)). From these findings we can conclude that
      antibodies against IFN-alpha are present in considerable number at low titer in
      accepted blood donors.

PMID- 21872226
TI  - In vitro and in vivo pro-angiogenic effects of thymosin-beta4-derived peptides.
AB  - Thymosin-beta4 (Tbeta4) is a G-actin sequestering peptide involved in
      regeneration and remodeling of injured tissues. In this work, we have designed
      and synthesized three peptide sequences containing the N-terminus (TYB4-n), the
      central part (TYB4-i) or the C-terminus (TYB4-c) of Tbeta4. All fragments are
      overlapping on the main central binding actin site. After a structural
      characterization, we have evaluated in vitro and in vivo their pro-angiogenic
      effects. The results of this study have shown that: (i) each fragment reproduces
      the native conformation; (ii) Tbeta4-derived peptides exert both in vitro and in
      vivo pro-angiogenic effects; (iii) their in vitro effect seem to be related to
      the activation of several signaling pathways and is positively modulated by the N
      terminus of Tbeta4.

PMID- 21872227
TI  - Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung
      function measures in urban family children.
AB  - PURPOSE: Understanding the interplay between genes and in-utero tobacco exposure
      in affecting child lung development is of great significance. In this study, we
      tested the hypothesis that tobacco-related lung-function reduction in children
      differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and
      Glutathione S-transferase Mu 1 (GSTM1). MATERIALS AND METHODS: Data were
      collected among 370 children (6-10 years old, 81.6% African-Americans) and their
      biological mothers visiting a large children's hospital. Study hypotheses were
      tested using multiple regression method. RESULTS: Among the study sample, 143
      mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric
      measures (mean+/-SD) included were: forced vital capacity (FVC)=1635+/-431 mL,
      forced expiratory volume in the first 1s (FEV1)=1440 +/-360 mL, percent FEV1/FVC
      ratio=89+/-12, and forced expiratory flow between the 25% and 75% of FVC (FEF25
      75)=1745+/-603 mL. In addition to a tobacco effect on FVC (-131 mL, 95% CI: -245,
      -17) and FEV1/FVC ratio (42, 95% CI: 1, 83), regression analysis controlling for
      covariates indicated that for the subsample of children whose mothers were
      CYP1A1*2A homozygous, maternal daily smoking was associated with -734 mL (95% CI:
      -1206, -262) reductions in FEV1 and -825 mL (95% CI: -909, -795) reductions in
      FVC; reduced smoking was still associated with -590 mL (95% CI: -629, -551)
      reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily
      smoking was associated with -176 mL (95% CI: -305, -47) reductions in FVC.
      DISCUSSION AND CONCLUSIONS: Maternal smoking during pregnancy was significantly
      associated with lung-function reduction in children, particularly for those whose
      mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion.

PMID- 21872228
TI  - Prevalence of the metabolic syndrome in women with a previous diagnosis of
      polycystic ovary syndrome: long-term follow-up.
AB  - OBJECTIVE: To examine the prevalence of the metabolic syndrome (MetS) according
      to the scientific statement of the American Heart Association and the US National
      Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish
      women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison
      with age-matched healthy controls. DESIGN: Long-term follow-up study. SETTING:
      Department of Obstetrics and Gynecology, Uppsala University. PATIENT(S): Eighty
      four women diagnosed with PCOS between 1987 and 1995; and 87 controls randomly
      selected from the general population. INTERVENTION(S): Anthropometric
      measurements and blood tests. MAIN OUTCOME MEASURE(S): Body mass index, waist
      circumference, blood pressure, lipids, and glucose. RESULT(S): The prevalence of
      MetS in women with PCOS (mean +/- SD age, 43.0 +/- 5.8 years) was 23.8% and in
      controls was 8.0%, and it did not differ according to PCOS phenotype at the index
      assessment (polycystic ovaries [PCO], oligomenorrhea, and hirsutism: 10 [22.7%];
      PCO and oligomenorrhea: 8 [22.2%]) or according to the persistence of PCOS
      features at follow-up (persisting PCOS: 25.8%; resolved PCOS: 16.7%).
      CONCLUSION(S): The MetS occurred more often in patients with PCOS than in
      controls and did not depend on phenotypic presentation at the index assessment or
      the persistence of PCOS at follow-up.

PMID- 21872229
TI  - Use of preimplantation genetic diagnosis and preimplantation genetic screening in
      the United States: a Society for Assisted Reproductive Technology Writing Group
      paper.
AB  - OBJECTIVE: To comprehensively report Society for Assisted Reproductive Technology
      (SART) member program usage of preimplantation genetic testing (PGT),
      preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and
      preimplantation genetic screening for aneuploidy (PGS). DESIGN: Retrospective
      study. SETTING: United States SART cohort data. PATIENT(S): Women undergoing a
      PGT cycle in which at least one embryo underwent biopsy. INTERVENTION(S): PGT.
      MAIN OUTCOME MEASURE(S): PGT use, indications, and delivery rates. RESULT(S): Of
      190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to
      SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined
      indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy
      screening (PGS), 527 for translocation, and 1,417 for elective sex election.
      Although the total number of fresh, autologous cycles increased by 3.6% from 2007
      to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and
      4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from
      4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary
      indication for PGT was PGS: cycles performed for this indication decreased (
      8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%),
      and translocation analysis (+0.5%) increased. PGT usage varied significantly by
      geographical region. CONCLUSION(S): PGT usage in the United States decreased
      between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection
      increased. High transfer cancellation rates correlated with reduced live-birth
      rates for some PGT indications.

PMID- 21872230
TI  - Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer
      cells: a meta-analysis.
AB  - OBJECTIVE: To determine whether preoperative hysteroscopic examination increases
      the risk for peritoneal dissemination of endometrial cancer cells and the effect
      of hysteroscopy on disease prognosis. DESIGN: Meta-analysis. SETTING: Literature
      search conducted via domestic and international databases for studies on
      preoperative hysteroscopy. PATIENT(S): A total of 2,944 women with endometrial
      cancer enrolled in selected studies. INTERVENTION(S): Preoperative hysteroscopic
      examination for 1,099 patients. MAIN OUTCOME MEASURE(S): Rate of positive
      peritoneal cytology. RESULT(S): Of 308 studies retrieved, 19 were included in the
      meta-analysis. The meta-analysis demonstrated that hysteroscopy resulted in a
      statistically significantly higher rate of positive peritoneal cytology results
      compared with no hysteroscopy. In addition, when a liquid medium was used for
      uterine distention during hysteroscopy, the difference between the two groups
      remained statistically significant. However, no statistically significant
      differences were seen when inflation pressure reached or exceeded 100 mm Hg or
      when the cancer stage was early. Trials that examined long-term outcomes reported
      no statistically significant differences in disease prognosis between the two
      groups. CONCLUSION(S): Hysteroscopic examination before surgery in patients with
      endometrial cancer may increase the risk of dissemination of malignant cells into
      the peritoneal cavity. The risk was statistically significantly associated with
      the use of a liquid medium for uterine cavity distention but not with early-stage
      disease. There is no evidence to support an association between preoperative
      hysteroscopic examination and a worse prognosis. There is no reason to avoid
      diagnostic hysteroscopy before to surgery in patients with endometrial cancer,
      especially in early stages.

PMID- 21872231
TI  - Endometrial polyps in infertile patients: do high concentrations of interferon
      gamma play a role?
AB  - OBJECTIVE: To assess levels of interferon-gamma (IFN-gamma) both in serum and in
      endometrial biopsy samples from infertile patients with endometrial polyps, to
      investigate the molecular background involved in the formation of endometrial
      polyps and its potential role in infertility. DESIGN: Prospective controlled
      trial. SETTING: Academic infertility clinic. PATIENT(S): Twenty-one infertile
      women affected by endometrial polyposis represented the study group, and 21
      homogeneous women without endometrial polyps were enrolled as control subjects.
      INTERVENTION(S): Blood and endometrial biopsy collection from infertile women
      with and without endometrial polyps. MAIN OUTCOME MEASURE(S): IFN-gamma-positive
      cells were analyzed and counted as spot-forming colonies. RESULT(S): IFN-gamma
      levels were significantly higher both in serum and in tissue biopsies of women
      with endometrial polyps. CONCLUSION(S): High concentrations of IFN-gamma were
      detected in infertile patients with endometrial polyps. The possible role of an
      inflammatory factor in a proliferative pathology represents a novel insight into
      the understanding of endometrial polyposis and its relationship with infertility.

PMID- 21872232
TI  - Factors contributing to failure of vacuum delivery and associated
      maternal/neonatal morbidity.
AB  - OBJECTIVE: To determine factors contributing to the failure of vacuum delivery
      and to compare the neonatal and maternal morbidity associated with failed and
      successful procedures. METHODS: A retrospective case-control study was undertaken
      at Aga Khan University Hospital, Nairobi, Kenya, by review of medical charts from
      the period of January 2007 to December 2010. In total, 31 cases of failed vacuum
      delivery were compared with 124 controls where extraction was successful. The
      primary outcome measure was fetal malposition. Secondary outcome measures
      included a composite score of maternal complications, a 5-minute Apgar score
      below 7, an umbilical arterial pH below 7.1, and a base excess below -12.
      Multiple logistic regression analysis was undertaken to identify factors
      associated with failure of vacuum delivery. RESULTS: Demographic and labor
      characteristics were similar in both groups. Fetal malposition significantly
      contributed to the failure of vacuum delivery (odds ratio 12.7, 95% confidence
      interval 1.5-14.8). Failure of vacuum delivery was not associated with clinically
      important neonatal or maternal morbidity. CONCLUSIONS: Vacuum extraction is a
      safe mode of delivery where indicated, with minimal maternal and neonatal
      morbidity even in the event of procedural failure.

PMID- 21872233
TI  - A 5-day educational program for teaching cervical cancer screening using visual
      inspection with acetic acid in low-resource settings.
AB  - OBJECTIVE: To assess the effectiveness of an educational program in visual
      inspection with acetic acid (VIA) for cervical cancer screening among healthcare
      providers in 2 low-resource countries. METHODS: A cohort of multidisciplinary
      healthcare workers in Uganda and El Salvador were recruited to the study. A
      pretest was administered before the intervention of a 5-day educational program
      on VIA. A posttest was performed immediately after the educational program and
      again at a 6-month follow-up visit to assess retention of knowledge. RESULTS: In
      total, 42 (93%) of the healthcare workers who participated in the educational
      program completed the initial posttest evaluation, and 18 (40%) healthcare
      workers completed the 6-month follow-up evaluation. Mean test scores increased
      after participation in the training session (62% versus 81%; P<0.001). The self
      reported comfort level for identifying cellular abnormalities also increased (2.1
      versus 3.3; P<0.001). At 6-month follow-up, the mean test score remained higher
      than pretest scores (79% versus 57%; P<0.001). There was no significant
      difference in the initial and 6-month posttest scores (80% versus 79%; P=0.20).
      CONCLUSION: The educational program in VIA provided healthcare workers with the
      tools potentially to decrease the morbidity and mortality of cervical cancer in
      the 2 low-resource countries.

PMID- 21872234
TI  - Stillbirth rate at an emerging tertiary health institution in Enugu, southeast
      Nigeria.
AB  - OBJECTIVES: To determine the stillbirth rate and factors predisposing to a
      stillbirth delivery at a teaching hospital in Nigeria, with the aim of
      identifying solutions. METHOD: A descriptive study of all stillbirths delivered
      at Enugu State University of Science and Technology Teaching Hospital, Parklane,
      Nigeria between January 1 and December 31, 2009. The sociodemographic
      characteristics of the mothers were documented and the possible causes of death
      were analyzed. RESULTS: There were 153 stillbirths and 2064 total deliveries,
      giving a stillbirth rate of 74 per 1000 deliveries. Of the stillbirths, 52.3%
      were fresh and 47.7% were macerated. Women who had not received prenatal care had
      a significantly higher stillbirth rate (P<0.05). The most likely cause of a
      macerated stillbirth was a hypertensive disorder of pregnancy, whereas the likely
      causes of fresh stillbirths were labor-related. The "3 levels of delay" and
      injudicious use of oxytocin in labor contributed to the intrapartum stillbirths
      (P<0.05). CONCLUSION: The stillbirth rate recorded in the study institution is
      unacceptably high. Appropriate prenatal care, timely intervention, and prompt and
      appropriate intrapartum care are key to achieving a reduction in the stillbirth
      rate.

PMID- 21872235
TI  - Management of ovarian carcinoid syndrome.

PMID- 21872236
TI  - H1N1 influenza pandemic and maternal mortality in Antioquia, Colombia.
AB  - OBJECTIVE: To evaluate the impact of the H1N1 influenza pandemic on maternal
      mortality in the province of Antioquia, Colombia, in 2009. METHODS: The present
      study was a descriptive, retrospective, cross-sectional study of maternal deaths
      in Antioquia in 2009 caused by H1N1-related pneumonia. The study formed part of
      the epidemiologic surveillance process undertaken by the Health and Social
      Protection Directorate of Antioquia and the particular healthcare institutions
      involved in the cases. RESULTS: In 2009, there were 42 maternal deaths in
      Antioquia, corresponding to a maternal mortality ratio of 46 per 100 000 live
      births. Ten deaths were due to pneumonia, 9 of which occurred after the H1N1
      outbreak was first reported in early 2009. In 3 cases, the women were confirmed
      to have H1N1 virus infection, and the remainder fulfilled probable case criteria.
      The main factors contributing to the deaths were underestimation of H1N1
      symptoms, and delays in administration of antiviral medication and in
      hospitalization. CONCLUSION: For the population subgroup of pregnant women in
      Antioquia, it is crucial to remain alert regarding H1N1 virus infection,
      guaranteeing patients adequate monitoring and/or timely administration of
      immunization, medication, and hospitalization.

PMID- 21872237
TI  - Ovarian cancer during pregnancy.
AB  - OBJECTIVE: To evaluate the clinical features, pregnancy outcome, and treatment of
      patients with ovarian cancer diagnosed during pregnancy. METHODS: The present
      study was a retrospective review of 11 cases of ovarian cancer detected during
      pregnancy. The women were treated and followed up at Selcuk University, Meram
      Faculty of Medicine, Konya, Turkey, during 2006-2010. RESULTS: Approximately half
      the patients were asymptomatic (5 [45.5%]) and diagnosed during cesarean delivery
      (6 [54.5%]). The histopathologic tumor categories comprised malignant epithelial
      ovarian tumor (4 [36.4%]), borderline tumor (4 [36.4%]), malignant germ cell
      tumor (2 [18.2%]), and sex cord stromal tumor (1 [9.1%]). Nine (81.8%) tumors
      were classified as stage I. Conservative surgery was performed in 10 (90.9%)
      patients. A patient with stage IIIC serous papillary adenocarcinoma underwent
      hysterectomy with bilateral salpingo-oophorectomy. A patient with dysgerminoma in
      stage IV died on follow-up. Three infants were born premature; they were followed
      up in the neonatal intensive care unit with satisfactory outcomes. CONCLUSION:
      Early diagnosis and appropriate treatment are crucial for patients with ovarian
      cancer diagnosed during pregnancy. Tumor staging is possible during pregnancy,
      but the appropriateness of surgery needs to be considered carefully. Ideally, the
      treatment strategy should be discussed and structured on an individual basis.

PMID- 21872238
TI  - Medicines used by pregnant women attending a district hospital in Ghana.

PMID- 21872239
TI  - A national review of cesarean delivery in Ethiopia.
AB  - OBJECTIVE: To describe Ethiopian national population-based and institutional
      cesarean delivery rates by sector, and to describe indications for cesarean
      delivery, fetal and maternal outcomes, and aspects of quality of care. METHODS:
      The data source was the national baseline assessment of emergency obstetric and
      newborn care--a cross-sectional, facility-based survey of 797 facilities. Two
      instruments were used to collect the data for the present paper: a retrospective
      record review of 267 cesarean deliveries based on the last 3 performed in each
      facility; and a 12-month summary of each facility's statistics on vaginal and
      abdominal deliveries. RESULTS: The national population-based cesarean delivery
      rate was 0.6%, with regional rates varying from 0.2% to 9%. The overall
      institutional rate was 18%, which varied between 46% in the private for- profit
      sector and 15% in the public sector. Maternal indications accounted for 66% of
      the cesareans reviewed, and fetal indications for 34%. Three-quarters of the
      cesareans were recorded as emergencies, but only 12% of these had their labor
      monitored with a partograph. The interval between decision and delivery was
      within 30 minutes for 36% of the women, 31-60 minutes for 23%, and more than 5
      hours for 19%. Antibiotics were given in 94% of the reviewed cases; nevertheless,
      12% of the cases reported wound infection. There were 2 maternal deaths and 14%
      of the newborns were stillbirths or died shortly after birth. CONCLUSION: The
      study showed little progress in the proportion of all births delivered by
      cesarean and a high rate of cesarean among women attended in the private sector-
      indicating a need to monitor the appropriateness of obstetric care in all sectors
      and to increase access in rural areas. Clinical management protocols for
      obstetric and newborn care are needed, and audits of cesareans should be
      performed at all institutions, especially in the private sector. The importance
      of improving record keeping is crucial for informed local decision-making.

PMID- 21872240
TI  - Complications among adolescents using copper intrauterine contraceptive devices.
AB  - OBJECTIVE: To evaluate the rate and pattern of complications associated with use
      of the Copper T 380A intrauterine device (IUD) among adolescents. METHODS: A
      prospective comparative study of women eligible for IUD insertion who attended
      the family planning clinic of Sohag University Hospital, Egypt, between July 1,
      2008 and December 31, 2010. The participants were categorized as adolescents or
      adults. The Copper T 380A IUD was inserted in all participants and follow-up
      visits were scheduled at 1, 3, and 6 months. Odds ratio and chi(2) square tests
      were used to compare the rates of complications at each visit. RESULTS: Of 1512
      patients eligible for IUD insertion, 852 met the inclusion criteria: 281
      adolescents and 571 adults. The rates of pain, bleeding, displacement, expulsion,
      and removal of IUDs were significantly higher in adolescents (P<0.05). The rates
      of these complications were high in adolescents younger than 16 years; the rates
      then decreased with age and became comparable with the adult rates at 18 years of
      age. CONCLUSIONS: IUD-associated complications were high in adolescents up to the
      age of 17 years. Our data suggest that adolescents younger than 18 years of age
      should be counseled carefully before IUD insertion, and examined more frequently
      to detect displacement or expulsion of the device.

PMID- 21872241
TI  - A clinicopathologic study of gynecologic organ involvement at radical cystectomy
      for bladder cancer.
AB  - OBJECTIVE: To report the clinicopathologic analysis of women who underwent
      radical cystectomy for bladder cancer in Egypt from 1997 to 2005. METHODS:
      Clinicopathologic data for 250 women who underwent radical cystectomy for bladder
      cancer at 3 centers in Cairo were retrospectively reviewed from hospital charts
      and pathology sheet records. Cystectomy specimens were evaluated pathologically
      for involvement of internal genitalia. RESULTS: The uterus was not available for
      histopathologic examination in 11 specimens; 1 ovary was absent from 18
      specimens; and both ovaries were absent from 2 specimens. Uterine involvement was
      observed in 1 case of transitional cell carcinoma. Benign uterine pathology was
      detected in 25 cases. All patients had normal ovaries, and the vagina was
      involved in 11 cases. There was urethral involvement in 10% of patients. Of the
      50 patients available for follow-up, 11 had 1 ovary preserved and 2 had the
      uterus plus both ovaries preserved. None of them experienced late ovarian or
      uterine recurrence. CONCLUSION: Involvement of female internal genitalia in
      bladder cancer is uncommon. Thus, preservation of these organs in young women
      undergoing radical cystectomy should be considered in selected cases after
      careful preoperative assessment.

PMID- 21872242
TI  - Averting maternal death and disability.

PMID- 21872243
TI  - Influence of ethnicity on the clinical and biologic expression of pre-eclampsia
      in the ECLAXIR study.
AB  - OBJECTIVE: To determine whether ethnic origin is related to the clinical and
      biologic expression of pre-eclampsia. METHODS: In a secondary analysis of
      information collected in the ECLAXIR study in France between May 2003 and October
      2006, the data from 284 white European, 84 Maghrebian and 158 African women were
      evaluated in a case-control study of the genetic and endothelial determinants of
      pre-eclampsia. RESULTS: African origin was a risk factor for pre-eclampsia before
      28 weeks of gestation. Symptoms related to hypertension, such as neurologic signs
      and changes in biologic parameters (e.g. hemolysis elevated liver enzymes, low
      platelet count [HELLP] syndrome), occurred more frequently among white European
      women. After logistic regression, gestational age at delivery was lower for
      African women than for white European women (33.4 weeks versus 34.4 weeks of
      gestation, P=0.04). CONCLUSION: The results suggest that ethnic origin may have a
      role in the expression of pre-eclampsia, and should therefore be taken into
      account in prenatal surveillance. Further research on the genetic factors
      involved in endothelial dysfunction is warranted.

PMID- 21872244
TI  - Oral misoprostol for the management of incomplete abortion in Ecuador.
AB  - OBJECTIVE: To assess the feasibility of introducing misoprostol for the treatment
      of incomplete abortion in Quito, Ecuador. METHODS: In a randomized prospective
      study conducted at a large tertiary-level maternity hospital and a private
      secondary-level clinic between November 2006 and November 2007, women with
      incomplete abortion were treated with either 600 MUg of oral misoprostol (n=122)
      or manual vacuum aspiration (MVA) (n=120). All participants were requested to
      return for follow-up care on day 7 to determine the success of the treatment and
      to document their satisfaction with the method and the adverse effects
      experienced. RESULTS: Sixteen percent of women (39/242) did not return for their
      follow-up visit and their outcomes are unknown. Among those who did return, 94%
      (100/106) of women showed successful completion of abortion after treatment with
      misoprostol, as compared with 100% (97/97) of women treated with MVA. Most women
      described their adverse effects after treatment as tolerable (misoprostol, 95%;
      MVA, 91%). Nearly all women reported being satisfied with their treatment
      (196/203); there were no differences among the women's reports of satisfaction
      according to treatment received. CONCLUSION: An oral dose of 600 MUg of
      misoprostol was found to be an acceptable and effective non-surgical option for
      treating incomplete abortion. Clinical trials.gov NCT00674232.

PMID- 21872245
TI  - HPV genotyping in neuroendocrine carcinoma of the uterine cervix in northern
      Thailand.
AB  - OBJECTIVE: To determine the distribution of HPV genotypes in cervical
      neuroendocrine carcinoma (NECA) in northern Thailand, and evaluate the
      correlation between HPV genotype and clinicopathologic features. METHODS: Samples
      from 111 women treated for cervical NECA at Chiang Mai University Hospital
      between 1992 and 2009 were tested for HPV genotype. Samples were formaldehyde
      fixed, paraffin-embedded, and tested via nested PCR and dot blot hybridization.
      RESULTS: Ninety-seven of the 111 samples were adequate for DNA analysis. HPV DNA
      was detected in 93 samples, of which 76 (81.7%) were single, 14 (15.1%) were
      multiple, and 3 (3.2%) were untyped infections. HPV18 was the most common subtype
      (70 cases, 75.3%), followed by HPV16 (28 cases, 30.1%). Other genotypes included
      HPV58 (3.2%), HPV52 (2.1%), and HPV33 (1.1%). Collectively, HPV16 and/or HPV18
      were found in 83 cases (89.3%). Women with HPV18 infection were significantly
      younger (42.0years) than those with non-HPV18 infections (54.1years) (P=0.003).
      Associated adenocarcinoma in situ was more frequently seen among women with HPV18
      infection (P=0.034). CONCLUSIONS: HPV18 infection was predominant in cervical
      NECA. Variations in HPV genotype may be related to the clinicopathologic features
      and pathogenetic pathways of NECA. Vaccination against HPV16 and HPV18 might
      provide protection against cervical NECA in almost 90% of cases.

PMID- 21872246
TI  - Distribution of human papillomavirus genotypes in archival cervical tissue from
      women with cervical cancer in urban Sri Lanka.
AB  - OBJECTIVE: To identify the contributions of various human papillomavirus (HPV)
      genotypes in tissue samples from women diagnosed with cervical cancer in Sri
      Lanka. METHODS: In a retrospective study, archival cervical tissues samples
      (n=108) obtained from Sri Lankan women diagnosed with histologically proven
      invasive squamous cell carcinoma between 2006 and 2007 were tested for HPV.
      Genotyping of HPV DNA was performed using an INNO-LiPA assay. RESULTS: Overall,
      93% of tumor samples tested positive for HPV DNA. HPV types 16 and 18 accounted
      collectively for 83.4% of the positive samples. CONCLUSION: The findings suggest
      that the HPV genotypes responsible for causing cervical cancer in Sri Lanka are
      similar to those reported elsewhere worldwide. Consequently, women in Sri Lanka
      could benefit from currently available prophylactic HPV vaccines should they be
      implemented.

PMID- 21872247
TI  - Clinical presentation of molar pregnancy at a teaching hospital in Iran, 1996
      2006.

PMID- 21872248
TI  - Malignant transformation of an endometriotic lesion derived from an abdominal
      wall scar.

PMID- 21872250
TI  - High serum level of lutein may be protective against early atherosclerosis: the
      Beijing atherosclerosis study.
AB  - OBJECTIVE: We investigated whether early atherosclerosis before calcified plaque
      appeared as assessed by carotid intima-media thickness (IMT) was associated with
      levels of the major carotenoids, and assessed the associations among these serum
      carotenoids, carotid IMT, and arterial stiffness. METHODS: The case-control study
      comprised 125 subjects with early atherosclerosis and 107 controls aged 45-68
      years. We simultaneously measured common carotid IMT and arterial stiffness by
      carotid ultrasonography, and serum carotenoids were determined by high-pressure
      liquid chromatograph (HPLC). RESULTS: In cases of early atherosclerosis, serum
      level of lutein was significantly lower than that in controls. Serum lutein was
      inversely associated with carotid IMT. Zeaxanthin and beta-carotene were both
      negatively correlated with right common carotid artery stiffness beta, elastic
      modulus (E(p)), and pulse wave velocity (PWV). After adjusting for age and
      gender, the associations remain significantly (P<0.05). However, there is no
      significant difference for zeaxanthin and beta-carotene between the cases and
      controls. CONCLUSION: These findings suggest that lutein may play a protective
      role in the prevention of early atherosclerosis, and the associations between
      serum carotenoids and arterial stiffness remained to be investigated.

PMID- 21872249
TI  - Molecular imaging with optical coherence tomography using ligand-conjugated
      microparticles that detect activated endothelial cells: rational design through
      target quantification.
AB  - OBJECTIVES: Optical coherence tomography (OCT) is a high resolution imaging
      technique used to assess superficial atherosclerotic plaque morphology. Utility
      of OCT may be enhanced by contrast agents targeting molecular mediators of
      inflammation. METHODS AND RESULTS: Microparticles of iron oxide (MPIO; 1 and 4.5
      MUm diameter) in suspension were visualized and accurately quantified using a
      clinical optical coherence tomography system. Bound to PECAM-1 on a plane of
      cultured endothelial cells under static conditions, 1 MUm MPIO were also readily
      detected by OCT. To design a molecular contrast probe that would bind activated
      endothelium under conditions of shear stress, we quantified the expression (basal
      vs. TNF-activated; molecules MUm(-2)) of VCAM-1 (not detected vs. 16 +/- 1);
      PECAM-1 (132 +/- 6 vs. 198 +/- 10) and E-selectin (not detected vs. 46 +/- 0.6)
      using quantitative flow cytometry. We then compared the retention of antibody
      conjugated MPIO targeting each of these molecules plus a combined VCAM-1 and E
      selectin (E+V) probe across a range of physiologically relevant shear stresses.
      E+V MPIO were consistently retained with highest efficiency (P < 0.001) and at a
      density that provided conspicuous contrast effects on OCT pullback. CONCLUSION:
      Microparticles of iron oxide were detectable using a clinical OCT system.
      Assessment of binding under flow conditions recommended an approach that targeted
      both E-selectin and VCAM-1. Bound to HUVEC under conditions of flow, targeted 1
      MUm E+V MPIO were readily identified on OCT pullback. Molecular imaging with OCT
      may be feasible in vivo using antibody targeted MPIO.

PMID- 21872251
TI  - A novel type of familial hypercholesterolemia: double heterozygous mutations in
      LDL receptor and LDL receptor adaptor protein 1 gene.
AB  - BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) is an extremely rare
      inherited hypercholesterolemia, the cause of which is mutations in low-density
      lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. METHODS: A total of
      146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in
      LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin
      type 9 (PCSK9) and LDLRAP1. RESULTS: Among the 146 subjects, we identified a 79
      year-old Japanese female with double mutations in LDLR gene (c.2431A>T) and
      LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes
      in her family were also identified. Although the proband exhibited massive
      Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C
      level of subjects with double mutations was similar with that of subjects with
      single LDLR mutation (284.0+/-43.5 versus 265.1 +/- 57.4 mg/dl). CONCLUSION:
      Additional mutation in LDLRAP1 may account for severer phenotype in terms of
      xanthoma and atherosclerotic cardiovascular disease in FH patients.

PMID- 21872252
TI  - Overexpression of CREG attenuates atherosclerotic endothelium apoptosis via
      VEGF/PI3K/AKT pathway.
AB  - AIMS: Cellular repressor of E1A-stimulated genes (CREG) is a homeostasis
      modulating gene abundantly expressed in adult artery endothelium. Previous
      studies have demonstrated a protective effect of CREG against atherosclerosis
      through prevention of vascular smooth muscle cell apoptosis. However, the role of
      CREG in endothelial cells (ECs) apoptosis and the underlying signaling mechanisms
      are unknown. METHOD AND RESULTS: We ascertained that CREG expression was
      decreased in atherogenesis-prone endothelium in apolipoprotein E-null (apoE(-/-))
      mice compared with their wild-type littermates using in situ immunofluorescent
      staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling (TUNEL) staining and caspase-3 activity assays determined that treatment
      of apoE(-/-) mice arteries with staurosporine (STS) significantly induced
      endothelial apoptosis associated with a reduction of CREG expression. Gain- and
      loss-of-function analyses revealed that silencing CREG expression significantly
      enhanced ECs apoptosis, whereas CREG overexpression abrogated apoptosis
      stimulated by STS or etoposide (VP-16). Blocking assays using the neutralizing
      antibody for vascular endothelial growth factor (VEGF) and the specific inhibitor
      of phosphoinositide 3-kinase (PI3K), such as LY294002 or wortmannin, demonstrated
      that the protective effect of CREG on ECs apoptosis was mainly mediated by
      activation of the VEGF/PI3K/AKT signaling pathway. CONCLUSIONS: These data
      demonstrate that CREG plays a critical role in protecting the vascular
      endothelium from apoptosis, and the protective effort of CREG against ECs
      apoptosis is through the activation of the VEGF/PI3K/AKT signaling pathway.

PMID- 21872253
TI  - Kinetic investigation of narrow-bore columns packed with prototype sub-2 MUm
      superficially porous particles with various shell thickness.
AB  - The recent successful breakthrough of sub-3 MUm shell particles in HPLC has
      triggered considerable research efforts toward the design of new brands of core
      shell particles. We investigated the mass transfer mechanism of a few analytes in
      narrow-bore columns packed with prototype 1.7 MUm shell particles, made of 1.0,
      1.2, and 1.4 MUm solid nonporous cores surrounded by porous shells 350, 250, and
      150 nm thick, respectively. Three probe solutes, uracil, naphthalene, and
      insulin, were chosen to assess the kinetic performance of these columns. Inverse
      size exclusion chromatography, peak parking experiments, and the numerical
      integration of the experimental peak profiles were carried out in order to
      measure the external, internal, and total column porosities, the true bulk
      diffusion coefficients of these analytes, the height equivalent to a theoretical
      plate, the longitudinal diffusion term, and the trans-particle mass transfer
      resistance term. The residual eddy diffusion term was measured by difference. The
      results show the existence of important trans-column velocity biases (7%)
      possibly due to the presence of particle multiplets in the slurry mixture used
      during the packing process. Our results illustrates some of the difficulties
      encountered by scientists preparing and packing shell particles into narrow-bore
      columns.

PMID- 21872254
TI  - Rapid and sensitive determination of posaconazole in patient plasma by capillary
      electrophoresis with field-amplified sample stacking.
AB  - The high morbidity and mortality associated with invasive fungal infections have
      increased the importance of improving treatment efficacy. Posaconazole is a novel
      agent with strong antifungal activity and low toxicity. The success of
      posaconazole pharmacotherapy strongly depends on precise controlling of
      concentration of the drug in the blood. In the present study, a solid phase
      extraction-capillary electrophoresis (SPE-CE) method was developed for rapid and
      accurate determination of posaconazole in the plasma of patients. We used the
      field-amplified sample stacking (FASS) technique to improve the sensitivity of
      CE, and applied the SPE procedures to reduce the matrix effect that was
      frequently encountered by biological samples in FASS system. Effect of filter
      types on the recovery rate of compounds with high lipophilicity was carefully
      investigated. Parameters affecting FASS performance were all optimized to obtain
      the best sensitivity with the highest speed. When using 1.25 M formic acid as the
      background electrolyte and 0.2 M formic acid in 95% (v/v) methanol as the sample
      solution, the limit of detection (LOD) for posaconazole was 10 ngmL(-1), with an
      analytical run time of less than 5 min. The relative standard deviation (RSD) of
      the peak area ratios for repeatability (intra-day, n=6) and intermediate
      precision (inter-day, n=3) were lower than 7.2% and 7.5%, respectively. The
      accuracy was tested by recovery, and the recovery rates were within 95.1% and
      106.4%, respectively. The successful application of the developed method
      demonstrated its feasibility as an effective method for clinical use.

PMID- 21872255
TI  - Determination of organophosphorus pesticides in bovine tissue by an on-line
      coupled matrix solid-phase dispersion-solid phase extraction-high performance
      liquid chromatography with diode array detection method.
AB  - A miniaturized method based on matrix solid-phase dispersion coupled to solid
      phase extraction and high performance liquid chromatography with diode array
      detection (MSPD-SPE-HPLC/DAD) was developed for the trace simultaneous
      determination of the following organophosphorus pesticides (OPPs) in bovine
      tissue: parathion-methyl, fenitrothion, parathion, chlorfenvinphos, diazinon,
      ethion, fenchlorphos, chlorpyrifos and carbophenothion. To perform the coupling
      between MSPD and SPE, 0.05 g of sample was dispersed with 0.2 g of C(18) silica
      sorbent and packed into a stainless steel cartridge containing 0.05 g of silica
      gel in the bottom. After a clean-up of high and medium polarity interferences
      with water and an acetonitrile:water mixture, the OPPs were desorbed from the
      MSPD cartridge with pure acetonitrile and directly transferred to a dynamic
      mixing chamber for dilution with water and preconcentration into an SPE 20 mm *
      2.0 mm I.D. C(18) silica column. Subsequently, the OPPs were eluted on-line with
      the chromatographic mobile phase to the analytical column and the diode array
      detector for their separation and detection, respectively. The method was
      validated and yielded recovery values between 91% and 101% and precision values,
      expressed as relative standard deviations (RSD), which were less than or equal to
      12%. Linearity was good and ranged from 0.5 to 10 MUg g(-1), and the limits of
      detection of the OPPs were in the range of 0.04-0.25 MUg g(-1). The method was
      satisfactorily applied to the analysis of real samples and is recommended for
      food control, research efforts when sample amounts are limited, and laboratories
      that have ordinary chromatographic instrumentation.

PMID- 21872256
TI  - Analysis of co-eluted isomers of high-molecular weight polycyclic aromatic
      hydrocarbons in high performance liquid chromatography fractions via solid-phase
      nanoextraction and time-resolved Shpol'skii spectroscopy.
AB  - We present an accurate method for the determination of isomers of high-molecular
      weight polycyclic aromatic hydrocarbons co-eluted in HPLC fractions. The
      feasibility of this approach is demonstrated with two isomers of molecular weight
      302 with identical mass fragmentation patterns, namely dibenzo[a,i]pyrene and
      naphtho[2,3-a]pyrene. Qualitative and quantitative analysis is carried out via
      laser-excited time-resolved Shpol'skii spectroscopy at liquid helium temperature.
      Unambiguous identification of co-eluted isomers is based on their characteristic
      4.2 K line-narrowed spectra in n-octane as well as their fluorescence lifetimes.
      Pre-concentration of HPLC fractions prior to spectroscopic analysis is performed
      with the aid of gold nanoparticles via an environmentally friendly procedure. In
      addition to the two co-eluted isomers, the analytical figures of merit of the
      entire procedure were evaluated with dibenzo[a,l]pyrene, dibenzo[a,h]pyrene and
      dibenzo[a,e]pyrene. The analytical recoveries from drinking water samples varied
      between 98.2+/-5.5 (dibenzo[a,l]pyrene) and 102.7+/-3.2% (dibenzo[a,i]pyrene).
      The limits of detection ranged from 51.1 ng L(-1) (naphtho[2,3-a]pyrene) to 154
      ng L(-1) (dibenzo[a,e]pyrene). The excellent analytical figures of merit
      associated to its HPLC compatibility makes this approach an attractive
      alternative for the analysis of co-eluted isomers with identical mass spectra.

PMID- 21872257
TI  - From brain to food: analysis of phosphatidylcholins, lyso-phosphatidylcholins and
      phosphatidylcholin-plasmalogens derivates in Alzheimer's disease human post
      mortem brains and mice model via mass spectrometry.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disorder
      characterized by extracellular senile plaques mainly consisting of Abeta, a 40-42
      amino acid long peptide, and intracellular neurofibrillary tangles, accompanied
      by an excessive loss of synapses. Recently evidence accumulated that nutrition,
      especially polyunsaturated fatty acids, influences AD pathogenesis. Especially
      mid-life food habits with the consumption of specific fatty acids (FA) appear to
      influence the disease risk. The timely separation between food intake and disease
      makes a direct correlation with detailed analysis of eating habits combined with
      accurate food analysis nearly unattainable. A possible solution to circumvent
      these difficulties is to investigate the FA composition in human post mortem
      brain. In this study we focused on the main phospholipids phosphatidylcholin
      (PC), phosphatidylcholin-plasmalogen (PC-PL) and lyso-phosphatidylcholin (lyso
      PC) in AD brains compared to control brains. Frontal cortices, temporal cortices
      and cerebellum of 30 AD (mean 78 years) and 14 control aged matched brains (mean
      77.4 years) as well as APP transgenic mice compared to control mice were analyzed
      using an AB Sciex 4000 Qtrap mass spectrometer utilizing a FIA MS/MS method. PC,
      PC-PL and lyso-PC metabolites were analyzed in respect to saturation level and FA
      composition. As expected, the majority of the lipid species showed no significant
      differences, but interestingly a few species revealed a highly significant
      reduction in AD brains. These FAs are potential candidates for further food
      analysis in respect to AD pathology. Additionally, we show that the method
      applied with multiple reaction monitoring (MRM) used for this study is suitable
      for semi quantitative analysis of small amounts (10 MUl) of brain tissue.

PMID- 21872258
TI  - A general strategy for performing temperature-programming in high performance
      liquid chromatography--prediction of segmented temperature gradients.
AB  - In the present work it is shown that the linear elution strength (LES) model
      which was adapted from temperature-programming gas chromatography (GC) can also
      be employed to predict retention times for segmented-temperature gradients based
      on temperature-gradient input data in liquid chromatography (LC) with high
      accuracy. The LES model assumes that retention times for isothermal separations
      can be predicted based on two temperature gradients and is employed to calculate
      the retention factor of an analyte when changing the start temperature of the
      temperature gradient. In this study it was investigated whether this approach can
      also be employed in LC. It was shown that this approximation cannot be
      transferred to temperature-programmed LC where a temperature range from 60
      degrees C up to 180 degrees C is investigated. Major relative errors up to 169.6%
      were observed for isothermal retention factor predictions. In order to predict
      retention times for temperature gradients with different start temperatures in
      LC, another relationship is required to describe the influence of temperature on
      retention. Therefore, retention times for isothermal separations based on
      isothermal input runs were predicted using a plot of the natural logarithm of the
      retention factor vs. the inverse temperature and a plot of the natural logarithm
      of the retention factor vs. temperature. It could be shown that a plot of lnk vs.
      T yields more reliable isothermal/isocratic retention time predictions than a
      plot of lnk vs. 1/T which is usually employed. Hence, in order to predict
      retention times for temperature-gradients with different start temperatures in
      LC, two temperature gradient and two isothermal measurements have been employed.
      In this case, retention times can be predicted with a maximal relative error of
      5.5% (average relative error: 2.9%). In comparison, if the start temperature of
      the simulated temperature gradient is equal to the start temperature of the input
      data, only two temperature-gradient measurements are required. Under these
      conditions, retention times can be predicted with a maximal relative error of
      4.3% (average relative error: 2.2%). As an example, the systematic method
      development for an isothermal as well as a temperature gradient separation of
      selected sulfonamides by means of the adapted LES model is demonstrated using a
      pure water mobile phase. Both methods are compared and it is shown that the
      temperature-gradient separation provides some advantages over the isothermal
      separation in terms of limits of detection and analysis time.

PMID- 21872259
TI  - Synthesis and luminescence properties of Eu(III)-doped nanoporous silica spheres.
AB  - Europium (III) (Eu(3+))-doped nanoporous silica spheres were synthesized, and the
      states of Eu(3+) ions in the silica framework structure were investigated. The
      ordered nanopores were preserved with the doping at the Eu(3+) molar
      concentration to Si up to 10 mol%, and the O-Si-O and Si-OH groups in the
      structures were clearly rearranged with the doping, indicating the interaction of
      Eu(3+) with the O atoms. The significant morphological changes in the spheres
      were observed with the doping. The photoluminescence spectral shapes due to the
      transitions of (5)D(0)-(7)F(1) and (5)D(0)-(7)F(2) were indicative of the
      presence of the Eu(3+) in an environment of a low symmetry. It was found that the
      Eu(3+) was located inside the silica framework to electrostatically interact with
      the environmental O atoms, which would prevent the aggregation among Eu(3+) ions
      to show the efficient luminescence. Therefore, the interactions between the
      Eu(3+) ions and silica framework structures in the spheres were successfully
      clarified.

PMID- 21872260
TI  - Drastic difference in porous structure of calcium alginate microspheres prepared
      with fresh or hydrolyzed sodium alginate.
AB  - Fresh or hydrolyzed sodium alginate was used as a material for preparing calcium
      alginate microspheres, and a drastic difference in porous structure was observed
      between them, even though the other materials and the preparation method except
      for the sodium alginate were exactly the same. When fresh sodium alginate was
      used, nonporous microspheres were obtained. In contrast, when 82-day-hydrolyzed
      sodium alginate, whose molecular weight became 7% of the molecular weight of the
      fresh sodium alginate, was used, porous microspheres with 6.5 times larger BET
      surface area were obtained. XPS studies indicated that the atomic ratio of Ca,
      the crosslinker of the alginic acid polymer, was almost the same in both cases.
      Therefore, the difference in porous structure was not attributed to the amount of
      crosslinking points, but to the low-molecular-weight compounds formed by
      hydrolysis, and they would work as pore-generating agents.

PMID- 21872261
TI  - Nanostructure of polysaccharide complexes.
AB  - The interaction of gum arabic (GA) with chitosan (Ch) of different degree of
      deacetylation was studied by turbidity measurements, dynamic light scattering and
      atomic force microscopy. The structure of the complexes was found to be directly
      related to the charge density of chitosan molecules. Gum arabic and chitosan with
      a degree of deacetylation of 75% form soluble complexes with a loosely globular
      structure of about 250 nm, at weight ratios up to 1.2, if the concentrations are
      kept low (total biopolymer concentration up to 0.06%). If chitosan has a higher
      charge density (degree of deacetylation of 93%), colloidal particles are formed,
      independently of the polymer concentration or ratio. At low concentrations and
      GA/Ch ratios of 1 or 1.2, the particles have diameters of 200-250 nm. The
      formation of soluble complexes is attributed to a chitosan lower charge density
      and the presence of non-charged monomers, which prevent the efficient self
      assembly of the macromolecules.

PMID- 21872262
TI  - Iron-dextran complex: geometrical structure and magneto-optical features.
AB  - Molecular mass of the iron-dextran complex (M(w)=1133 kDa), diameter of its
      particles (~8.3 nm) and the content of iron ions in the complex core (N(Fe)=6360)
      were determined by static light scattering, measurements of refractive index
      increment and the Cotton-Mouton effect in solution. The known number of iron ions
      permitted the calculation of the permanent magnetic dipole moment value to be
      MU(Fe)=3.17*10(-18) erg Oe(-1) and the determination of anisotropy of linear
      magneto-optical polarizabilities components as Deltachi=9.2*10(-21) cm(3).
      Knowing both values and the value of the mean linear optical polarizability
      alpha=7.3*10(-20) cm(3), it was possible to show that the total measured CM
      effect was due to the reorientation of the permanent and the induced magnetic
      dipole moments of the complex. Analysis of the measured magneto-optical
      birefringence indicated very small optical anisotropy of linear optical
      polarizability components, kappa(alpha), which suggested a homogeneous structure
      of particles of spherical symmetry.

PMID- 21872263
TI  - Inducible atrial tachycardias with multiple circuits in a stepwise approach are
      associated with increased episodes of atrial tachycardias after catheter
      ablation.
AB  - BACKGROUND: Atrial tachycardia (AT) is commonly observed during catheter ablation
      (CA) in patients with atrial fibrillation (AF) undergoing a stepwise extensive
      CA. In this study, we examined the hypothesis that the presence of multiple
      inducible ATs (multiple-ATs), which allow for latent multiple reentrant circuits,
      might increase the potential for following AT episodes after CA. METHODS AND
      RESULTS: The study population consisted of 347 consecutive AF patients undergoing
      CA with a stepwise approach. A total of 366 ATs (tricuspid isthmus dependent,
      101; mitral annulus, 62; septal, 26; roof dependent, 22; left atrial anterior
      wall, 13; upper loop, 8; surrounding the left pulmonary veins, 6; surrounding the
      right pulmonary veins, 6; left atrial appendage, 4; and Cs ostium, 3) occurring
      during the CA were found in 216 (62.2%) of 347 patients. Multiple-ATs (>=2)
      during the CA were observed in 93 (26.8%) of 347 patients. The incidence of AT
      episodes significantly increased as the number of inducible ATs increased (no AT,
      7.8%; single AT, 13.7%; and multiple-ATs, 24.2%; P < .001), and multiple-ATs were
      an independent risk factor for AT episodes (3.07 [1.39-6.78]; P = .005). The
      impact of the multiple-ATs on the AT episodes was pronounced especially in the
      patients with coinducible residual AF (with coresidual AF vs without coresidual
      AF, 8.1% vs 47.7%; P < .001). CONCLUSIONS: The presence of an atrial substrate
      allowing for multiple-ATs was associated with increased AT episodes during follow
      up.

PMID- 21872264
TI  - Do elevated glucocorticoids contribute to reduced cerebral expression of insulin
      degrading enzyme in schizophrenia?

PMID- 21872266
TI  - Nitric oxide synthase expression in rat anorectal tissue after sacral
      neuromodulation.
AB  - BACKGROUND: Sacral neuromodulation is becoming established as a valid treatment
      option for patients with anorectal disorders. Nevertheless, despite its efficacy,
      little is known regarding its mechanism of action. The purpose of this study was
      to evaluate whether chronic sacral neuromodulation is able to influence the
      expression of nitric oxide synthetase (NOS) in the anorectum of rats. MATERIALS
      AND METHODS: Twenty-six female Sprague-Dawley rats were divided into three
      groups; normal control rats (n = 6); sham treatment (n =10) and group in whom,
      electrical sacral neuromodulation was performed (n = 10). Bilateral electrode
      wires were placed in the S1 and electrical stimulation was performed for 14 d. At
      the end of the procedures the rats were sacrificed, proctectomy was performed,
      and anorectal specimens were sent to the laboratory for immunostaining with n-NOS
      and i-NOS. RESULTS: In the anal and rectal specimens, n-NOS and i-NOS expression
      was significantly increased in epithelial and muscle cells after neuromodulation
      of the anus and rectum of the animals. CONCLUSION: Our results showed that this
      model can be applied in further experimental studies to better understand the
      mechanism of action of sacral neuromodulation in anorectal disorders.

PMID- 21872265
TI  - Age-related Notch-4 quiescence is associated with altered wall remodeling during
      vein graft adaptation.
AB  - BACKGROUND: The link of aging to specific mechanisms of vascular biology is not
      well understood. We have previously shown that aging is associated with increased
      vein graft wall thickness and that this process involves the VEGF-Delta/Notch
      ephrin/Eph cascade. Therefore, we examined whether Dll-4 or Notch-4 are
      differentially expressed, according to age, during vein graft adaptation.
      MATERIALS AND METHODS: Vein grafts were performed in 6-mo and 24-mo Fischer 344
      rats. Gene expression was analyzed by quantitative real-time PCR, and the
      distribution of Dll-4 and Notch-4 was observed by immunofluorescence. RESULTS:
      The expression of Dll-4 and Notch-4 was reduced in vein grafts performed in aged
      rats compared with the expression in young adult rats. Both Dll-4 and Notch-4
      were distributed in vein graft endothelium as well as the outer adventitia, with
      reduced amounts in the outer adventitia of aged vein grafts. Aged veins had
      reduced eNOS membrane targeting and colocalization with caveolin-1 as well as
      reduced eNOS protein expression in comparison to young adult veins. In an
      exchange model between young and aged animals, heterogeneous vein grafts (Yo(Ag)
      and Ag(Yo)) showed significantly thicker neointima compared with young (Yo(Yo))
      controls, and had Notch-4-positive cells, but not Dll-4-positive cells,
      diminished in the adventitia. Vein grafts that were air-denuded of endothelium
      did not show any adaptation to the arterial environment and also lacked both Dll
      4 and Notch-4 expression at 3 wk. CONCLUSIONS: During vein graft adaptation to
      the arterial environment, both Dll-4 and Notch-4 expression are down-regulated in
      an aged, but not a young, background. Loss of Notch-4 is associated with loss of
      attenuation of neointima. The delta-Notch signaling pathway may be active during
      vein graft adaptation.

PMID- 21872267
TI  - Microbiology of smegma in boys in Kano, Nigeria.
AB  - BACKGROUND: The objective of this study is to document the common bacteria found
      in the smegma in the subpreputial space of asymptomatic boys in our environment,
      their antimicrobial susceptibility pattern, and to determine if they differ from
      those commonly isolated from children with established urinary tract infections
      in our sub-region. MATERIALS AND METHODS: Between May 2009 and January 2010,
      smegma swabs were collected from asymptomatic boys who presented for circumcision
      in our institution. This was done using aseptic techniques in the theatre,
      following retraction of the prepuce. The swabs were immediately sent to our
      microbiology laboratory for microscopy, culture, and sensitivity tests. Bacteria
      were isolated, identified, and confirmed by standard bacteriological techniques,
      and antimicrobial sensitivity pattern was determined using the disc diffusion
      method. A total of 52 boys, with an age range of 7 d to 11 y (median 138.7d),
      were recruited into the study. RESULTS: A total of 50 bacterial isolates were
      made. There were 29 gram-positive bacteria (58%) and 21 gram-negative ones (42%).
      A single isolate was found in 34 boys (65.4%), eight had a mixed isolate (15.4%),
      while no bacteria was isolated in 10 boys (19.2%). The most commonly isolated
      gram-negative bacteria was Escherichia coli (90.5%), while the commonly isolated
      gram-positive bacteria were Staphylococcus epidermidis (44.8%) and Staphylococcus
      aureus (41.4%). Most of the bacterial isolates were multi-drug-resistant.
      CONCLUSION: Smegma in the preputial space of children may be colonized by drug
      resistant organisms, the antimicrobial sensitivity pattern of which must be
      determined for an effective treatment of any infection arising in the region.

PMID- 21872268
TI  - Immunosuppressive effects of ginsenoside-Rd on skin allograft rejection in rats.
AB  - BACKGROUND: Organ transplantation is a life-saving procedure for patients with
      organ failure. However, the side effects of long-term application of classic
      immunosuppressant remain major obstacles for successful transplantation.
      Therefore, new and safe immunosuppressive drugs against acute and chronic
      rejection are eagerly awaited. MATERIALS AND METHODS: In the present study, we
      detected the effect of ginsenoside-Rd on mitogen-induced mouse spleen lymphocytes
      proliferation in vitro and observed the effect of ginsenoside-Rd on allograft
      rejection in a rat skin transplantation model. Th1/Th2 type cytokines secretion
      and T-cell subsets were also detected. RESULTS: The results showed that
      ginsenoside-Rd could markedly inhibit Concanavalin A (ConA)-induced mouse spleen
      T lymphocytes proliferation. Also, ginsenoside-Rd could significantly prolong the
      mean survival time of skin allograft and improve the skin allograft pathological
      damage. Furthermore, ginsenoside-Rd could markedly suppress alloantigen-specific
      production of Th1 cytokines IL-2 and IFN-gamma as well as proinflammatory
      cytokines TNFalpha and IL-12. In parallel, Th2 cytokine IL-10 production in serum
      of rat recipients was markedly up-regulated. Ginsenoside-Rd at a dose of 25 mg/kg
      could significantly reduce the percentages of CD4(+) T cells and CD8(+) T cells
      in peripheral blood of rat recipients. CONCLUSIONS: Our results suggest that
      ginsenoside-Rd can effectively antagonize transplant rejection, which might
      qualify ginsenoside-Rd as a putative, therapeutic drug for the treatment of Th1
      driven diseases, including transplant rejection.

PMID- 21872269
TI  - Dietary flaxseed protects against lung ischemia reperfusion injury via inhibition
      of apoptosis and inflammation in a murine model.
AB  - BACKGROUND: The hallmark of lung ischemia-reperfusion injury (IRI) is the
      production of reactive oxygen species (ROS), and the resultant oxidant stress has
      been implicated in apoptotic cell death as well as subsequent development of
      inflammation. Dietary flaxseed (FS) is a rich source of naturally occurring
      antioxidants and has been shown to reduce lung IRI in mice. However, the
      mechanisms underlying the protective effects of FS in IRI remain to be
      determined. METHODS: We used a mouse model of IRI with 60 min of ischemia
      followed by 180 min of reperfusion and evaluated the anti-apoptotic and anti
      inflammatory effects of 10% FS dietary supplementation. RESULTS: Mice fed 10% FS
      undergoing lung IRI had significantly lower levels of caspases and decreased
      apoptotic activity compared with mice fed 0% FS. Lung homogenates and
      bronchoalveolar lavage fluid analysis demonstrated significantly reduced
      inflammatory infiltrate in mice fed with 10% FS diet. Additionally, 10% FS
      treated mice showed significantly increased expression of antioxidant enzymes and
      decreased markers of lung injury. CONCLUSIONS: We conclude that dietary FS is
      protective against lung IRI in a clinically relevant murine model, and this
      protective effect may in part be mediated by the inhibition of apoptosis and
      inflammation.

PMID- 21872270
TI  - Technical pearls for swine lung transplantation.
AB  - BACKGROUND: Since the advent of ex vivo lung perfusion (EVLP), there has been
      increased focus on swine models of lung transplantation; however, the anatomic
      differences between human and swine lungs and the technical challenges in
      performing porcine lung transplantation are not well described in the surgical
      literature. METHODS: Surgically important anatomic variations are described, and
      the technical measures taken to address them during harvest and transplantation
      are introduced. RESULTS: There are three surgically important anatomic variations
      in pigs. First, the right cranial lobe bronchus arises directly from the trachea,
      which makes right lung transplantation technically challenging if not
      prohibitive. Second, the left hemi-azygos vein is fully developed and courses
      upward through the posterior mediastinum, where it crosses the left pulmonary
      hilum and drains directly into the coronary sinus. During transplantation, this
      vein is ligated and dissected away to expose the underlying left pulmonary hilar
      structures. Third, the right inferior pulmonary vein crosses the midline to drain
      into the left atrium immediately adjacent to the left inferior pulmonary vein.
      During donor lung preparation, the right inferior pulmonary vein is ligated
      distally from the left atrium, which leaves an adequate atrial cuff around the
      left sided pulmonary veins for later anastomosis. CONCLUSION: Experimental
      porcine lung transplantation is technically demanding. We have found recognition
      of the above described anatomical differences and technical nuances facilitate
      transplantation and provide reproducible results.

PMID- 21872271
TI  - Predictors of positive head CT scan and neurosurgical procedures after minor head
      trauma.
AB  - BACKGROUND: There continues to be an ongoing debate regarding the utility of head
      CT scans in patients with a normal Glasgow Coma Scale (GCS) after minor head
      injury. The objective of this study is to determine patient and injury
      characteristics that predict a positive head CT scan or need for a neurosurgical
      procedure (NSP) among patients with blunt head injury and a normal GCS. MATERIALS
      AND METHODS: Retrospective analysis of adult patients in the National Trauma Data
      Bank who presented to the ED with a history of blunt head injury and a normal GCS
      of 15. The primary outcomes were a positive head CT scan or a NSP. Multivariate
      logistic regression controlling for patient and injury characteristics was used
      to determine predictors of each outcome. RESULTS: Out of a total of 83,566
      patients, 24,414 (29.2%) had a positive head CT scan and 3476 (4.2%) underwent a
      NSP. Older patients and patients with a history of fall (compared with a motor
      vehicle crash) were more likely to have a positive finding on a head CT scan.
      Male patients, African-Americans (compared with Caucasians), and those who
      presented with a fall were more likely to have a NSP. CONCLUSIONS: Older age,
      male gender, ethnicity, and mechanism of injury are significant predictors of a
      positive finding on head CT scans and the need for neurosurgical procedures. This
      study highlights patient and injury-specific characteristics that may help in
      identifying patients with supposedly minor head injury who will benefit from a
      head CT scan.

PMID- 21872272
TI  - Prognosis of metastatic carcinoma of the lung in the bevacizumab era: comparison
      between the major histologic types of lung cancer.
AB  - BACKGROUND: In October 2006, bevacizumab was approved for treatment for patients
      with metastatic non-small-cell lung cancer other than squamous carcinoma. Our
      hypothesis was that the change in survival after approval of bevacizumab for
      metastatic adenocarcinoma would show differences from that of small-cell
      carcinoma and squamous carcinoma. METHODS: Data was obtained from the National
      Cancer Institute Surveillance Epidemiology and End Results (SEER) registry for
      patients with lung cancer diagnosed between January 2004 and November 2007. In
      addition to known characteristics predicting survival differences (histotype,
      age, gender, and race) we compared 1-year survival experience in those diagnosed
      before (January 2004-September 2006) and after (October 2006-November 2007)
      introduction of bevacizumab. RESULTS: Of 24,575 patients meeting criteria, 16,081
      (65.4%) died within 1 y. Adjusted for age, gender, and race, patients with
      squamous carcinoma showed a 13% decline (95% CI 7%-20%) in survival times. By
      contrast, the 1% increment for adenocarcinoma and the 1% decrement for small cell
      carcinoma might well have been due to chance (P > 0.05 for each analysis).
      CONCLUSIONS: Life expectancy for metastatic adenocarcinoma (for which bevacizumab
      is approved) and metastatic small-cell carcinoma (bevacizumab not approved) did
      not change statistically. On the other hand, life expectancy for patients with
      metastatic squamous carcinoma (bevacizumab not approved) of the lung has declined
      since the approval of bevacizumab. This likely reflects increased classification
      of tumors previously diagnosed as poorly differentiated non-small-cell carcinoma
      as poorly differentiated squamous carcinoma. Hence, life expectancy of metastatic
      adeno, squamous, and small-cell-lung cancer has not improved after introduction
      of bevacizumab.

PMID- 21872273
TI  - Sjogren-Larsson syndrome: novel mutations in the ALDH3A2 gene in a French cohort.
AB  - Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder
      characterized by ichthyosis, spastic di- or tetraplegia and mental retardation
      due a defect of the fatty aldehyde dehydrogenase (FALDH), related to mutations in
      the ALDH3A2 gene. In this study, we screened a French cohort of patients with
      Sjogren-Larsson syndrome (SLS) for mutations in the ALDH3A2 gene. The five
      unrelated patients with typical SLS all present mutations in this gene. Three
      novel mutations were identified whereas three other ones were previously
      described. We also realized functional analyses at the mRNA level for two splice
      site mutations to study their deleterious consequences. Two of the previously
      described mutations had already been identified in the same region of Europe,
      suggesting a putative founder effect. We suggest that, (1) when clinical and MR
      features are present, direct sequencing of the ALDH3A2 gene in SLS is of
      particular interest without necessity of a skin biopsy for enzymatic assay in
      order to propose genetic counsel and (2) identification of mutations already
      described in the same population with putative founder effects may simplify
      genetic analysis in this context.

PMID- 21872274
TI  - Evaluation of early dynamic changes of intracranial arterial occlusion is useful
      for stroke etiology diagnosis.
AB  - BACKGROUND AND PURPOSE: The etiologic diagnosis of intracranial arterial
      occlusion is sometimes challenging because of the dynamic nature of acute stroke.
      We investigated whether short-term follow-up vascular imaging adds additional
      information to the differential diagnosis between intracranial atherosclerotic
      and embolic occlusion. METHODS: Acute ischemic stroke patients with symptomatic
      middle cerebral artery (MCA) occlusion on MR angiography (MRA) within 24h of
      symptom onset were included. Follow-up MRA was performed 5-7days after stroke
      onset. Stroke subtypes were independently determined at baseline and follow-up
      MRAs based on clinical, laboratory and imaging findings. RESULTS: In the 108
      included patients, the most common etiologic subtype of initial stroke was
      intracranial large artery atherosclerosis (ICLAA) in 70 patients, followed by
      cardioembolism in 29 and other causes in 9. On follow-up MRA, 32 (29.6%) patients
      showed either significant or complete recanalization. Of these, 10 had been
      originally diagnosed with ICLAA, but were reclassified as a cryptogenic mechanism
      after follow-up MRA. Multiple logistic regression analysis showed that the
      presence of coexisting arterial atherosclerosis (odds ratio [OR], 6.91; 95%
      confidence interval [CI], 2.67-17.91; p<0.001); the absence of large territorial
      infarction (OR, 4.06; 95% CI, 1.39-11.85; p=0.010); and smoking (OR, 2.54; 95%
      CI, 1.028-6.29; p=0.043) were significantly associated with a final diagnosis of
      ICLAA. CONCLUSION: In the absence of follow-up vascular imaging, a substantial
      proportion of patients with intracranial middle cerebral arterial occlusion may
      be misdiagnosed as ICLAA. Evaluation of early dynamic changes in intracranial
      middle cerebral arterial occlusion may provide useful information for the
      differential diagnosis of intrinsic atherosclerosis and embolic occlusion.

PMID- 21872275
TI  - Trauma does not accelerate neuronal degeneration in Fig4 insufficient mice.
AB  - Fig4 null reduces phosphatidylinositol-3,5-diphosphate concentration and causes
      severe neuronal degeneration in both pale-tremor (plt) mice and patients with
      Charcot-Marie-Tooth disease type 4J (CMT4J), an inherited condition with
      recessive mutations in FIG4. Our previous study shows that minor trauma is
      associated with an accelerated course of motor neuron degeneration in patients
      with CMT4J. Heterozygous loss of FIG4 function has been suggested to be a risk
      factor in developing sporadic amyotrophic lateral sclerosis. We therefore
      hypothesize that minor trauma may trigger or exacerbate motor neuron degeneration
      in mice with fig4 haploinsufficiency (plt+/-). We have studied 18 wild-type and
      18 plt+/- mice and created nerve injury by compressing the sciatic nerve.
      Outcomes in the mice were evaluated by nerve conduction study, Rotarod, and nerve
      morphology. No differences were found between wild-type and plt+/- mice. Taken
      together, our results demonstrate that haploinsufficiency of fig4 does not impose
      risks in rodents to develop neuronal degeneration in either naive or traumatic
      conditions.

PMID- 21872276
TI  - Clinical approach to nonmotor sensory fluctuations in Parkinson's disease.
AB  - Many nonmotor fluctuations (NMFs) may occur in addition to the classic motor
      fluctuations (MFs) in patients with Parkinson's disease (PD) within several years
      of initiation of dopaminergic treatment. Patients can experience these NMFs in
      the "on" and/or "off" periods. NMFs can be divided into three groups: Autonomic,
      cognitive/psychiatric, and sensory. Nonmotor sensory fluctuations (NMSFs)
      occurring in association with "on" period are more frequently recognized than
      those in the "off" state. NMSFs commonly reported include pain, numbness,
      paresthesia/dysesthesia, akathisia, rest-legs syndrome (RLS), dyspnea, and
      internal tremor (IT). Proposed treatments of NMSFs are based on whether they
      occur during "off" or "on" state. These include reduction of dopaminergic
      medication, use of long-acting dopamine agonists or controlled released levodopa
      (LD), surgical intervention, and/or targeted pharmacological intervention to
      minimize dopaminergic side effects. NMSFs might be related to dopaminergic
      mechanisms although difficulty in managing these symptoms with dopaminergic
      therapy suggests a different pathway. CONCLUSION: Recognition of NMSFs is
      important in the care of patients with Parkinson disease to prevent unnecessary
      interventions and for appropriate medication regimen adjustments.

PMID- 21872277
TI  - Thirty- and ninety-day outcomes after sublobar resection with and without
      brachytherapy for non-small cell lung cancer: results from a multicenter phase
      III study.
AB  - OBJECTIVE: Sublobar resection (SR) is commonly used for patients considered high
      risk for lobectomy. Nonoperative therapies are increasingly being reported for
      patients with similar risk because of perceived lower morbidity. We report 30-
      and 90-day adverse events (AEs) from American College of Surgeons Oncology Group
      Z4032, a multicenter phase III study for high-risk patients with stage I non
      small cell lung cancer. METHODS: Data from 222 evaluable patients randomized to
      SR (n = 114) or SR with brachytherapy (n = 108) are reported. AEs were recorded
      using the Common Terminology Criteria for Adverse Events, Version 3.0, at 30 and
      90 days after surgery. Risk factors (age, percent baseline carbon monoxide
      diffusion in the lung [DLCO%], percent forced expiratory volume in 1 second
      [FEV1%], upper lobe vs lower lobe resections, performance status, surgery
      approach, video-assisted thoracic surgery vs open and extent, and wedge vs
      segmentectomy) were analyzed using a multivariable logistic model for their
      impact on the incidence of grade 3 or higher (G3+) AEs. Respiratory AEs were also
      specifically analyzed. RESULTS: Median age, FEV1%, and DLCO% were similar in the
      2 treatment groups. There was no difference in the location of resection (upper
      vs lower lobe) or the use of segmental or wedge resections. There were no
      differences between the groups with respect to "respiratory" G3+ AEs (30 days:
      14.9% vs 19.4%, P = .35; 0-90 days: 19.3% vs 25%, P = .31) and "any" G3+ AEs (30
      days: 25.4% vs 30.6%, P = .37; 0-90 days: 29.8% vs 37%, P = .25). Further
      analysis combined the 2 groups. Mortality occurred in 3 patients (1.4%) by 30
      days and in 6 patients (2.7%) by 90 days. Four of the 6 deaths were thought to be
      due to surgery. When considered as continuous variables, FEV1% was associated
      with "any" G3+ AE at days 0 to 30 (P = .03; odds ratio [OR] = 0.98) and days 0 to
      90 (P = .05; OR = 0.98), and DLCO% was associated with "respiratory" G3+ AE at
      days 0 to 30 (P = .03; OR = 0.97) and days 0 to 90 (P = .05; OR = 0.98).
      Segmental resection was associated with a higher incidence of any G3+ AE compared
      with wedge resection at days 0 to 30 (40.3% vs 22.7%; OR = 2.56; P < .01) and
      days 0 to 90 (41.5% vs 29.7%; OR = 1.96; P = .04). The median FEV1% was 50%, and
      the median DLCO% was 46%. By using these median values as potential cutpoints,
      only a DLCO% of less than 46% was significantly associated with an increased risk
      of "respiratory" and "any" G3+ AE for days 0 to 30 and 0 to 90. CONCLUSIONS: In a
      multicenter setting, SR with brachytherapy was not associated with increased
      morbidity compared with SR alone. SR/SR with brachytherapy can be performed
      safely in high-risk patients with non-small cell lung cancer with low 30- and 90
      day mortality and acceptable morbidity. Segmental resection was associated with
      increased "any" G3+ AE, and DLCO% less than 46% was associated with "any" G3+ AE
      and "respiratory" G3+ AE at both 30 and 90 days.

PMID- 21872279
TI  - Preresection serum C-reactive protein measurement and survival among patients
      with resectable non-small cell lung cancer.
AB  - OBJECTIVE: This study aimed to determine whether preresection serum CRP level
      independently predicts survival among patients with resectable non-small cell
      lung cancer. METHODS: Clinical, pathologic, and laboratory data from 300 patients
      operated on for non-small cell lung cancer in a single institution were studied
      in univariate and multivariate survival analyses. Validation was sought in
      another cohort of 68 similar patients from another institution. RESULTS: In the
      main cohort, preoperative CRP value was 3 mg/L or lower in 136 patients (45.3%),
      between 4 and 20 mg/L in 89 (29.7%), and greater than 20 in 64 (21.3%). CRP level
      was significantly associated with chronic bronchitis, hypoalbuminemia, pathologic
      stage, and peritumoral vascular emboli. Overall, 5-year survivals of patients
      with preoperative CRP 3 mg/L or lower, between 4 and 20 mg/L, and greater than 20
      mg/L were 55.6%, 45.6%, and 40.0%, respectively (P = .0571). In multivariate
      analysis, CRP level greater than 20 was significantly associated with survival,
      but with significant interaction between CRP level and disease stage (P = .02).
      Patients in stage I or II disease with CRP levels greater than 20 had worse
      survival than did patients with undetectable CRP (adjusted hazard ratio, 1.874;
      95% confidence interval, 1.039-3.381); the difference was not significant in
      stages III and IV. In the validation series, CRP level greater than 20 mg/L also
      predicted worse survival (P = .018). CONCLUSIONS: Preoperative CRP level greater
      than 20 mg/L is significantly associated with worse survival than undetectable
      CRP in patients with stage I or II non-small cell lung cancer.

PMID- 21872280
TI  - Extremely rare but potential complication of diffuse brain edema due to air
      embolism during lung segmentectomy with selected segmental inflation technique by
      syringe needle during video-assisted thoracoscopic surgery.

PMID- 21872282
TI  - Effect of normothermic cardiopulmonary bypass on renal injury in pediatric
      cardiac surgery: a randomized controlled trial.
AB  - OBJECTIVE: Hypothermic cardiopulmonary bypass (CPB), although associated with a
      reduction in oxygen requirement, has a number of disadvantages including
      detrimental effects on enzymatic function, energy generation, and cellular
      integrity. Normothermic perfusion is potentially a more physiologic method to
      maintain the functional integrity of major organ systems. One of the aims of this
      trial was to compare the effect of normothermic and hypothermic CPB on renal
      injury in pediatric patients undergoing cardiac surgery. METHODS: Fifty-nine
      children (median age, 78 months; interquartile range, 39-130) undergoing
      corrective cardiac surgery were randomized to either hypothermic (28 degrees C)
      or normothermic (35 degrees C-37 degrees C) CPB. Urinary albumin, retinal binding
      protein (RBP) and N-acetyl-beta-glucosaminidase (NAG) were measured
      preoperatively, end of CPB, 4, and 24 hours postoperatively and were expressed as
      a ratio of urinary creatinine. Serum creatinine was measured preoperatively, end
      of CPB, and 24 and 48 hours postoperatively. Results are expressed as a
      difference in means (normotheric - hypothermic) or as a ratio of geometric means
      (normothermic/hypothermic). RESULTS: Baseline characteristics were similar in
      both groups. For these biochemical markers no significant interactions between
      treatment and postintervention time were found. Serum creatinine (-2.10; 95%
      confidence interval [CI], -6.51-2.31), RBP (ratio, 0.96; 95% CI, 0.65-1.41), and
      NAG (ratio, 0.86; 95% CI, 0.56-1.36) were similar in the 2 groups (P >= .34), but
      the urinary albumin was significantly lower in the normothermic group (ratio,
      0.63; 95% CI, 0.42-0.95, P = .03). CONCLUSIONS: Normothermic CPB is associated
      with similar renal impairment to hypothermic CPB in children undergoing heart
      surgery.

PMID- 21872283
TI  - Tricuspid valve surgery: the past 10 years from the Nationwide Inpatient Sample
      (NIS) database.
AB  - OBJECTIVES: The purpose of this study was to examine the trends in tricuspid
      valve surgery over time. METHODS: We used 10 years (1999-2008) of NIS data to
      examine the population of patients undergoing tricuspid valve repair or
      replacement (ICD-9-CM codes 35.14, 35.27, and 35.28). RESULTS: We identified
      28,726 admissions for tricuspid valve surgery. The total number of tricuspid
      procedures more than doubled over the 10- year period (1712 cases in 1999 vs 4072
      cases in 2008). Although the absolute number of repairs and replacements
      increased over time, the tricuspid repair rate increased whereas there was a
      corresponding decrease in tricuspid replacement rate. Isolated tricuspid valve
      surgery accounted for 20% of the total tricuspid cases, whereas tricuspid surgery
      as a concomitant procedure to other cardiac operations accounted for the
      remaining 80%. There was a trend toward increased use of tissue over mechanical
      valves for tricuspid replacement. Overall hospital mortality was 10.6%. Over
      time, mortality decreased significantly for both repair and replacement.
      Concomitant tricuspid replacement was associated with significantly higher
      hospital mortality than was isolated tricuspid replacement (16.1% vs 10.1%; P =
      .0001). CONCLUSIONS: There has been a dramatic increase in tricuspid
      interventions over time. This has been associated with an increase in tricuspid
      repair rates as well as use of bioprostheses for tricuspid replacement. The
      majority of tricuspid operations are performed concomitantly to other cardiac
      procedures. Mortality for tricuspid valve surgery remains considerable and
      significantly higher for replacement than for repair.

PMID- 21872284
TI  - Aerobic exercise training increases circulating insulin-like growth factor
      binding protein-1 concentration, but does not attenuate the reduction in
      circulating insulin-like growth factor binding protein-1 after a high-fat meal.
AB  - Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects
      throughout the body, and its expression is regulated in part by insulin.
      Circulating IGFBP-1 predicts development of cardiometabolic diseases in
      longitudinal studies, and low IGFBP-1 concentrations are associated with insulin
      resistance and consumption of a high-fat diet. Because of the favorable metabolic
      effects of regular aerobic exercise, we hypothesized that aerobic exercise
      training would increase plasma IGFBP-1 concentrations and attenuate the reduction
      in IGFBP-1 after a high-fat meal. Ten overweight (body mass index = 28.7 +/- 0.9
      kg/m(2)), older (61 +/- 2 years) men and women underwent high-fat feeding and
      oral glucose tolerance tests at baseline and after 6 months of aerobic exercise
      training. In response to aerobic exercise training, subjects increased
      cardiorespiratory fitness by 13% (P < .05) and insulin sensitivity index by 28%
      (P < .05). Basal plasma concentrations of IGFBP-1 increased by 41% after aerobic
      exercise training (P < .05). The insulin response to an oral glucose tolerance
      test was a significant predictor of fasting plasma IGFBP-1 concentrations at
      baseline and after exercise training (P = .02). In response to the high-fat meal
      at baseline, plasma IGFBP-1 concentrations decreased by 58% (P < .001); a 61%
      decrease to similar postprandial concentrations was observed after exercise
      training (P < .001). Plasma insulin response to the high-fat meal was inversely
      associated with postprandial IGFBP-1 concentrations at baseline and after
      exercise training (P = .06 and P < .05, respectively). Although aerobic exercise
      training did not attenuate the response to a high-fat meal, the increase in IGFBP
      1 concentrations after exercise training may be one mechanism by which exercise
      reduces risk for cardiometabolic diseases in older adults.

PMID- 21872285
TI  - Empowering staff nurses to use research to change practice for safe patient
      handling.
AB  - Although evidence supports safe patient handling practices, nurses are not always
      involved in the process of evaluating and selecting lifting equipment. This study
      used a descriptive design to: (1) assess staff's perceived barriers and attitudes
      toward safe patient handling, (2) identify staff needs for equipment and
      education concerning safe patient handling, and (3) involve staff in the
      equipment selection process before implementing a safe patient handling program.
      Overall, staff on all units indicated that they wanted more equipment and
      education. Major barriers identified by staff were lack of: a "no lift" policy,
      adequate lifting equipment, and adequate space on patient care units. Staff had
      the opportunity to participate in a vendor fair and select equipment for trial.
      An appraisal was conducted with 2 vendors for trialing and evaluating the
      equipment. Nursing staff had the ability to participate in research and change
      practice for safe patient handling.

PMID- 21872286
TI  - Complementary public health: not what it seems.

PMID- 21872287
TI  - Detection of circoviruses and porcine adenoviruses in water samples collected
      from swine manure treatment systems.
AB  - Samples collected from two swine manure treatment systems including: swine manure
      treatment system and demonstrative unit (SMTS and DU), were analyzed by qPCR to
      quantify the amount of porcine adenovirus (PAdV) and porcine circovirus (PCV2)
      present. Positive samples were tested for virus integrity using DNase assay.
      Fifty-six water samples were collected monthly from March 2009 to May 2010. PAdV
      genome was found 66% of the samples in the SMTS and in 78% of the samples in the
      DU system. PCV2 was detected in 96% of samples collected from the SMTS system and
      in 86% of samples from DU. DNase assay revealed that there were undamaged virus
      particles of both PAdV and PCV2 in all sampling sites in the SMTS. However,
      undamaged particles of both viruses were detected in samples from the DU system
      in the affluent and middle sites, though undamaged PCV2 was absent in the
      effluent samples.

PMID- 21872288
TI  - Cell culture from lizard skin: a tool for the study of epidermal differentiation.
AB  - An in vitro system of isolated skin cells has been developed in order to address
      the understanding on the factors that control the shedding cycle and
      differentiation of lizard epidermis. The skin from the regenerating lizard tail
      has been separated in epidermis and dermis, cells have been dissociated,
      cultivated in vitro, and studied ultrastructurally after 1-30 days of culture
      condition. Dissociated keratinocytes after 12 days in culture show numerous cell
      elongations and contain bundles of keratin or sparse keratin filaments. These
      cells often contain one to three 0.5-3 MUm large and dense "keratinaceous
      bodies", an organelle representing tonofilament disassembling. Most keratinocytes
      have sparse tonofilaments in the cytoplasm and form shorter bundles of keratin in
      the cell periphery. The dissociated dermis mainly consists of mesenchymal cells
      containing sparse bundles of intermediate filaments. These cells proliferate and
      form multi-stratified layers and a dermal pellicle in about 2-3 weeks in vitro in
      our basic medium. Conversely, cultures of keratinocytes do not expand but
      eventually reduce to few viable cells within 2-3 weeks of in vitro condition. It
      is suggested that dermal cells sustain themselves through the production of
      growth factors but that epidermal cells requires specific growth factors still to
      be identified before setting-up an in vitro system that allows analyzing the
      control of the shedding cycle in lizards.

PMID- 21872289
TI  - The evaluation of cyclic uniaxial strain on myogenic differentiation of adipose
      derived stem cells.
AB  - It has been revealed that skeletal muscle cells have the potential to generate,
      sense and respond to biomechanical signals and that, mechanical force is one of
      the important factors influencing proliferation, differentiation, regeneration
      and homeostasis of skeletal muscle cells and myoblasts. The aim of this study was
      to illustrate the effect of cyclic uniaxial strain on myogenic differentiation of
      adipose-derived stem cells (ASCs). This study was designed to investigate this
      effect within 3 days in 4 groups: control (untreated), chemical, chemical
      mechanical and mechanical based on exposure of ASCs to chemical growth factors
      for 3 days or to mechanical strain just on the 2nd day. Finally, cell
      orientation, muscle-related gene expression, myosin protein synthesis and the
      number of myosin-positive cells were examined to estimate the rate of
      differentiation. By studying the cells before and after exposure to uniaxial
      strain, it could be observed that by exerting the load, the cells were organized
      almost perpendicularly to strain direction. Real-time RT-PCR demonstrated that
      uniaxial strain had a significant effect on up-regulation of muscle-related genes
      in chemical-mechanical group (P < 0.001) as compared to mechanical or chemical
      groups. Immunocytochemistry confirmed the myosin-positive cells in treated groups
      and the numbers of these cells were enumerated by flow cytometry. These data
      suggest that uniaxial cyclic strain could affect ASCs and cause their myogenic
      differentiation and that the combination of chemical myogenic differentiation
      factors with mechanical signals promotes differentiation much more than
      differentiation by chemical myogenic differentiation factors or mechanical
      signals alone.

PMID- 21872290
TI  - Molecular characterization of Drosophila cells persistently infected with Flock
      House virus.
AB  - Little is known about the molecular determinants causing and sustaining viral
      persistent infections at the cellular level. We found that Drosophila cells
      persistently infected (PI) with Flock House virus (FHV) invariably harbor
      defective viral RNAs, which are replicated by the FHV RNA-dependent RNA
      polymerase. Some defective RNAs encoded a functional B2 protein, the FHV
      suppressor of RNA interference, which might contribute to maintenance of virus
      persistence. Viral small interfering RNAs (vsiRNAs) of both polarities were
      detected in PI cells and primarily mapped to regions of the viral genome that
      were preserved in the isolated defective RNAs. This indicated that defective RNAs
      could represent major sources of vsiRNAs. Immunofluorescence analysis revealed
      that mitochondria and viral proteins are differentially distributed in PI cells
      and lytically infected cells, which may partly explain the reduction in
      infectious viral progeny. Our results provide a basis for further investigations
      of the molecular mechanisms underlying persistent infections.

PMID- 21872291
TI  - Evaluation of a laboratory-scale bioreactive in situ sediment cap for the
      treatment of organic contaminants.
AB  - The development of bioreactive sediment caps, in which microorganisms capable of
      contaminant transformation are placed within an in situ cap, provides a potential
      remedial design that can sustainably treat sediment and groundwater contaminants.
      The goal of this study was to evaluate the ability and limitations of a mixed,
      anaerobic dechlorinating consortium to treat chlorinated ethenes within a sand
      based cap. Results of batch experiments demonstrate that a tetrachloroethene
      (PCE)-to-ethene mixed consortium was able to completely dechlorinate dissolved
      phase PCE to ethene when supplied only with sediment porewater obtained from a
      sediment column. To simulate a bioreactive cap, laboratory-scale sand columns
      inoculated with the mixed culture were placed in series with an upflow sediment
      column and directly supplied sediment effluent and dissolved-phase chlorinated
      ethenes. The mixed consortium was not able to sustain dechlorination activity at
      a retention time of 0.5 days without delivery of amendments to the sediment
      effluent, evidenced by the loss of cis-1,2-dichloroethene (cis-DCE)
      dechlorination to vinyl chloride. When soluble electron donor was supplied to the
      sediment effluent, complete dechlorination of cis-DCE to ethene was observed at
      retention times of 0.5 days, suggesting that sediment effluent lacked sufficient
      electron donor to maintain active dechlorination within the sediment cap.
      Introduction of elevated contaminant concentrations also limited
      biotransformation performance of the dechlorinating consortium within the cap.
      These findings indicate that in situ bioreactive capping can be a feasible
      remedial approach, provided that residence times are adequate and that
      appropriate levels of electron donor and contaminant exist within the cap.

PMID- 21872292
TI  - Spatio-temporal variation in soil derived nitrous oxide emissions under
      sugarcane.
AB  - Nitrous oxide (N(2)O) is a significant greenhouse gas with a global warming
      potential that is 300 times than that of carbon dioxide. Soil derived N(2)O
      emissions usually display a high degree of spatial and temporal variability
      because of their dependence on soil chemical and physical properties, and climate
      dependent environmental factors. However, there is little research that
      incorporates spatial dependence in the estimation of N(2)O emissions allowing for
      environmental factors in the same model. This study aims to examine the impact of
      two environmental factors (soil temperature and soil moisture) on N(2)O emissions
      and explore the spatial structure of N(2)O in the sub-tropical South East
      Queensland region of Australia. The replicated data on N(2)O emissions and soil
      properties were collected at a typical sugarcane land site covering 25 uniform
      grid points across 3600 m(2) between October 2007 and September 2008. A Bayesian
      conditional autoregressive (CAR) model was used to model spatial dependence.
      Results showed that soil moisture and soil temperature appeared to have
      substantially different effects on N(2)O emissions after taking spatial
      dependence into account in the four seasons. There was a substantial variation in
      the spatial distribution of N(2)O emission in the different seasons. The high
      N(2)O emission regions were accompanied by high uncertainty and changed in
      varying seasons in this study site. Spatial CAR models might be more plausible to
      elucidate and account for the uncertainty arising from unclear variables and
      spatial variability in the assessment of N(2)O emissions in soils, and more
      accurately identify relationships with key environmental factors and help to
      reduce the uncertainty of the soil parameters.

PMID- 21872294
TI  - Hypertension incidence after tap-water implementation: a 13-year follow-up study
      in the arseniasis-endemic area of southwestern Taiwan.
AB  - Hypertension is the leading cause of cardiovascular disease worldwide. Long-term
      arsenic exposure has been linked to increased risk for hypertension; however,
      little is known whether a previous exposure has lingering effects on hypertension
      after the exposure being reduced significantly for decades. The study cohort was
      established in 1990 in an arseniasis-endemic area of 3 villages - Homei, Fuhsin,
      and Hsinming in Putai Township located on the southwestern coast of Taiwan, where
      residents were exposed to artesian well water (median level=700 to 930 MUg/L)
      until early 1970s. The original cohort consisted of 490 non-hypertensive
      residents over 30-yrs-old and 352 of them were successfully followed up in
      2002/03. Arsenic concentrations in the artesian well water consumed by residents
      during 1960s were used to indicate the previous exposure while urinary arsenic
      species measured in 2002/3 was used to represent current exposure. Hypertension
      incidences were 27.4, 65.6, and 69.1, per 1000 person-years for men aged 35-49,
      50-64, and 65-74 years, respectively being higher than the corresponding rates of
      25.1, 46.1, and 57.2 in a community-based longitudinal study. Cancer was the
      major cause of the total deaths (17/30=57%). Diastolic blood pressure was shown
      to increase with an increased cumulative arsenic ingestion from drinking water
      (beta=0.27, p<0.001). The incidence was increased by 2.43-fold in subjects of
      As(V)>=2.67 MUg/g creatinine as compared to those of As(V)<1.20 MUg/g creatinine
      (the third vs. first tertile; p=0.047) after adjustment for conventional risk
      factors. This study suggests that three decades after cessation of drinking
      artesian well water, residents of the endemic area are still at increased risk
      for developing hypertension, particularly those who excrete high amounts of
      As(V).

PMID- 21872295
TI  - Association of blood transfusion and venous thromboembolism after colorectal
      cancer resection.
AB  - INTRODUCTION: Red blood cell (RBC) transfusion is a common event in the
      perioperative course of patients undergoing surgery. Transfused blood can disrupt
      the balance of coagulation factors and modulates the inflammatory cascade. Since
      inflammation and coagulation are tightly coupled, we postulated that RBC
      transfusion may be associated with the development of venous thromboembolic
      phenomena. We queried the American College of Surgeons' National Surgical Quality
      Improvement Program (ACS NSQIP) database to examine the relationship between
      intraoperative blood transfusion and development of venous thromboembolism (VTE)
      in patients undergoing colorectal resection for cancer. MATERIALS AND METHODS: We
      analyzed the data from 2005 to 2009 for patients undergoing colorectal resections
      for cancer based on the primary procedure CPT-4 code and operative ICD-9
      diagnosis code. The primary outcome was 30-day deep vein thrombosis (DVT) and/or
      pulmonary embolism (PE). Intraoperative transfusion of RBC's was categorized as:
      none, 1-2 units, 3-5 units and 6 units or more. DVT/PE occurrences were analyzed
      by multivariable forward stepwise regression (p for entry<.05, for exit>.10) to
      identify independent predictors of DVT. RESULTS: The database contained 21943
      colorectal cancer resections. The DVT rate was 1.4% (306/21943) and the PE rate
      was 0.8% (180/21943). Patients were diagnosed with both only 40 times and the
      combined DVT or PE rate (VTE) was 2.0% (446/21943). After adjusting for age,
      gender, race, ASA (American Society of Anesthesiologists) class, emergency
      procedure, operative duration and complexity of the procedure (based on Relative
      Value Units, RVU's), along with six clinical risk factors, intraoperative blood
      transfusion was a significant risk factor for the development of VTE and the risk
      increased with increasing number of units transfused. Preoperative hematocrit did
      not enter the multivariable model as an independent predictor of VTE, nor did
      open versus laparoscopic resection or wound class. CONCLUSION: In this study of
      21943 patients undergoing colorectal resection for cancer, blood transfusion is
      associated with increased risk of VTE. Malignancy and surgery are known
      prothrombotic stimuli, the subset of patients receiving intraoperative RBC
      transfusion are even more at risk for VTE, emphasizing the need for sensible use
      of transfusions and rigorous thromboprophylaxis regimens.

PMID- 21872296
TI  - B and T lymphocytes in acquired thrombotic thrombocytopenic purpura during
      disease remission.

PMID- 21872297
TI  - Health care expenditures associated with venous thromboembolism among children.
AB  - INTRODUCTION: We used health insurance claims data from large samples of Medicaid
      enrolled and privately insured children to identify children with venous
      thromboembolism (VTE) and to assess their use of health services and associated
      expenditures during 2009. MATERIALS AND METHODS: Data from the 2009 Thomson
      Reuters MarketScan(r) Commercial Database and Multi-State Medicaid database were
      used to estimate annual expenditures for children 1-17 years of age with VTE.
      Generalized linear models were used to calculate adjusted annual expenditures for
      Medicaid-enrolled and privately insured children with VTE, controlling for age,
      sex, type of health plan, VTE classification (deep vein thrombosis and/or
      pulmonary embolism), and type of VTE event (idiopathic or secondary) and race
      (Medicaid only) or region (Commercial only). RESULTS: During 2009, Medicaid
      enrolled and privately insured children with VTE had an average of 1-2 inpatient
      admissions and 8-10 non-emergency department visits. Unadjusted mean total
      expenditures were similar for Medicaid-enrolled and privately insured children
      with VTE, $105,359 and $87,767, respectively. Adjusted mean expenditures for
      children with secondary VTE were five times higher than for children with
      idiopathic VTE. CONCLUSIONS: Given the high frequency of secondary VTE in
      children, most of the associated expenditures may be due to other health
      conditions. However, children who develop a VTE incur substantial costs of care,
      even in the absence of related conditions. Additional research is needed to
      evaluate the long term outcomes for children with VTE including rates of
      readmission, complications, and the impact of co-morbid conditions.

PMID- 21872298
TI  - A comparative study of antithrombotic and antiplatelet activities of different
      fucoidans from Laminaria japonica.
AB  - INTRODUCTION: Fucoidans extracted from brown algae represent an intriguing group
      of natural fucose-enriched sulfated polysaccharide, with excellent anticoagulant,
      antimetastatic, antiangiogenic and anti-inflammatory activities. In the present
      study, we compared antithrombotic activities of four fucoidan fractions with
      different molecular weight and sulfated ester content from Laminaria japonica in
      an electrical induced arterial thrombosis and their potential mechanism
      underlying such activity. RESULTS AND CONCLUSIONS: In vivo middle molecular
      weight (MMW) fucoidan fractions with molecular weight about 28000 and 35000
      exhibited better antithrombotic activity in electrical induced arterial
      thrombosis than low molecular weight (LMW) fucoidan LF1 and LF2 (Mw 7600 and
      3900). Inhibition of arterial thrombosis occurred at dose of 0.1-0.25mg/kg for
      MMW fucoidans, accompanied with moderate anticoagulant activity and significant
      decrease of whole blood viscosity and hematocrit. The antithrombotic effects of
      MMW Fucoidans might be related with promotion of TFPI content and decrease of
      TXB2 content, without affecting platelet aggregation and 6-keto-PGF1alpha content
      in vivo. In contrast, LMW fucoidans showed a correlation among anticoagulant,
      antiplatelet and antithrombotic effects in vivo. Antithrombotic action of LF1 and
      LF2 required high dose of 2.5-10mg/kg, concomitantly with anticoagulant activity
      and specific inhibition of platelet aggregation in vivo. Their antithrombotic
      effect might be related to their promotion of TFPI and 6-keto-PGF1alpha, down
      regulation of TXB2, without affecting hemorheology. These findings suggested that
      fucoidan fractions with different molecular weight acted on the antithrombotic
      action by different mechanism. By comparison, highly sulfated fucoidan LF2 with
      molecular weight of 3900 seemed to be a more suitable choice of antithrombotic
      drug for its antithrombotic activity accompanied with specific inhibitory
      activity on platelet aggregation, low anticoagulant activity and low hemorrhagic
      risk in vivo.

PMID- 21872299
TI  - Thrombin generation in severe sepsis.
AB  - INTRODUCTION: Hemostasis and inflammation are two tightly interrelated systems in
      the host's response to infection. Thrombin generation in sepsis plays a crucial
      role in enhancing and modulation of inflammation. The present study aimed to
      investigate the course of thrombin generation in patients with severe sepsis, and
      its correlation with outcome. MATERIALS AND METHODS: Thrombin generation was
      measured in platelet-poor plasma from 32 healthy controls and 75 patients with
      severe sepsis using the commercially available Calibrated Automated
      Thrombography. Samples were taken within 24 hours of the diagnosis of severe
      sepsis (t1) as well as on day 2 (t2), day 3 or 4 (t3) and between day 6 to 8
      (t4), while this was done only once in healthy controls. The assay was run with
      and without the addition of thrombomodulin. Clinical data were also collected at
      the same time points. RESULTS: Except for endogenous thrombin potential, there
      was significant difference between patients and controls regarding peak thrombin,
      lag time and time to thrombin peak. Twelve patients (16%) died in the ICU. There
      was no significant difference in endogenous thrombin potential between survivors
      and non-survivors of sepsis. Thrombin peak was higher in survivors than non
      survivors at all time points, with a significant difference at t2 and t4. The lag
      time and time to thrombin peak were shorter in non-survivors than in survivors at
      t1 and t3. CONCLUSIONS: While thrombin peak shows a positive correlation with
      survival, the lag phase and time to thrombin peak may be signs of impending DIC.
      The endogenous thrombin potential does not have any prognostic importance.

PMID- 21872300
TI  - Early stroke-related DVT is more than just DVT diagnosed early after stroke
      onset.

PMID- 21872301
TI  - Pleural ELFA D-dimer assay: a surrogate marker for malignant pleural effusion.
AB  - BACKGROUND: Malignant pleural effusion is associated with enhanced fibrinolysis.
      However, no data are available concerning the precise role of pleural D-dimer
      assay in pleural effusion. We therefore assessed the role of pleural D-dimer
      assay in predicting malignant pleural effusion. PATIENTS AND METHODS: A
      prospective laboratory investigation was conducted in a tertiary care teaching
      hospital. The study included consecutive patients with pleural effusion who
      presented at the Pulmonary Department between November 2009 and May 2010. Blood
      and pleural D-dimer levels were measured by Enzyme Linked Fluorescent assay
      (ELFA). The results were correlated with the clinical, laboratory, and
      radiological findings, and with the final diagnosis of the pleural fluid.
      RESULTS: A total of 103 patients with pleural effusion were included in the
      study. The Pleural ELFA D-dimer results were found to be positively correlated
      with pleural etiology of malignancy (p=0.0001). Pleural etiology was also
      correlated with pleural LDH, pleural protein, pleural PH, pleural glucose,
      pleural and blood CRP, but not with ADA. In a binary logistic regression, only
      the pleural ELFA D-dimer assay was a significant predictor of the malignant
      pleural effusion (odds ratio 1.007; 95% confidence interval 1.002-1.012;
      p=0.007). The area under the receiver operating characteristics curve for
      malignancy was 0.79. A D-dimer level of 146mg/ml had a sensitivity of 82% and a
      specificity of 74%. CONCLUSIONS: We found high D-dimer levels among malignant
      pleural effusion. D-dimer might be useful as a simple, noninvasive, surrogate
      marker for malignant pleural effusion.

PMID- 21872302
TI  - The procoagulant properties of purified fibrinogen concentrate are enhanced by
      carbon monoxide releasing molecule-2.
AB  - INTRODUCTION: Fibrinogen concentrate has been demonstrated to enhance coagulation
      in vitro and in several clinical settings of coagulopathy. We have recently
      demonstrated that carbon monoxide releasing molecule-2
      (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a
      substrate for thrombin via an attached heme. The objective of this study was to
      determine if CORM-2 modified fibrinogen concentrate would enhance coagulation
      more effectively than CORM-2 naive fibrinogen concentrate. MATERIALS AND METHODS:
      In the first series of experiments, fibrinogen concentrate (final concentration
      300mg/dl) was exposed to 0, 50 or 100MUM CORM-2 for 5min at 37 degrees C prior to
      being added to citrated, fibrinogen depleted plasma. In another series of
      experiments, citrated plasma obtained from 12 normal subjects was 50% diluted
      with crystalloid to which was added fibrinogen concentrate (final concentration
      300mg/dl) exposed to 0 or 100MUM CORM-2. Coagulation was activated with tissue
      factor (n=8 per condition). Thrombus growth was monitored with thrombelastography
      for 15min. RESULTS AND CONCLUSIONS: CORM-2 modification of fibrinogen concentrate
      significantly enhanced the velocity of clot formation (30-50%) and strength (15
      31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived
      thrombi demonstrated a marked decrease in velocity of formation (54%) and
      strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and
      strength (171%); however, CORM-2 modified fibrinogen concentrate significantly
      increased velocity (303%) and strength (205%) to a greater extent. Additional in
      vitro investigation and in vivo preclinical assessments of the hemostatic
      efficacy of CORM-2 modified fibrinogen concentrate are warranted.

PMID- 21872303
TI  - Distribution and variation in gonadotropin releasing hormone-I (GnRH-I)
      immunoreactive neurons in the brain of the native Thai chicken during the
      reproductive cycle.
AB  - Gonadotropin releasing hormone-I (GnRH-I) is known to regulate the avian
      reproductive system. We investigated the roles of GnRH-I in the regulation of the
      reproductive system of the native Thai chicken. The distribution of GnRH-I
      neurons and changes in GnRH-I-immunoreactive (-ir) neurons throughout the
      reproductive stages and between incubating and nest-deprived hens were analyzed
      utilizing immunohistochemical techniques. The results revealed that GnRH-I-ir
      neurons were distributed in a discrete region lying close to the third ventricle
      from the level of preoptic area through the anterior hypothalamus, with the
      greatest abundance found within the nucleus commissurae pallii (nCPa). The number
      of GnRH-I-ir neurons in the nCPa was highest in laying hens when compared with
      that in the other reproductive stages. Nest deprivation caused an increase in the
      number of GnRH-I-ir neurons in the nCPa of nest-deprived hens when compared with
      incubating hens. These results indicate that GnRH-I expression is correlated with
      the reproductive state in the native Thai chicken and may be, in part, regulated
      by it. This study also confirms a pivotal role of GnRH-I in controlling avian
      reproduction of this non-seasonal breeding, equatorial species.

PMID- 21872305
TI  - A fusion protein of flagellin and ovalbumin suppresses the TH2 response and
      prevents murine intestinal allergy.
AB  - BACKGROUND: The Toll-like receptor (TLR) 5 agonist flagellin is associated with
      immunomodulatory functions. OBJECTIVE: We sought to investigate whether Listeria
      monocytogenes-derived flagellin A (flaA) can modulate ovalbumin (OVA)-specific T
      cell responses and prevent OVA-induced intestinal allergy. METHODS: Bone marrow
      derived myeloid dendritic cells from BALB/c, C57BL/6, or TLR signaling-deficient
      (MyD88(-/-)) mice were stimulated with rOVA, rflaA, rflaA plus rOVA, or a
      recombinant fusion protein consisting of rflaA and rOVA (rflaA:OVA). The
      immunomodulating properties of rflaA plus rOVA and rflaA:OVA were investigated by
      means of DC-T-cell coculture with CD4(+) T cells from OVA-T-cell receptor
      transgenic or OVA/alum-immunized mice. rflaA:OVA was applied as a prophylactic
      and therapeutic vaccine in a murine model of intestinal allergy. RESULTS:
      rflaA:OVA induced upregulation of TLR5 and dose-dependent IL-6 and IL-10
      secretion by myeloid dendritic cells. IL-10 contributed to repressing IL-4 and
      IFN-gamma secretion by OVA-T-cell receptor transgenic CD4(+) T cells. Moreover,
      rflaA:OVA suppressed CD4(+) T cells derived from T(H)2-biased mice on OVA/alum
      immunization. In a murine model of intestinal allergy, prophylactic vaccination
      with rflaA:OVA reduced T-cell activation. Protection from intestinal allergy
      included suppression of OVA-specific IgE while inducing OVA-specific IgG(2a).
      Equimolar amounts of rflaA or rOVA provided alone or as a mixture did not have
      comparable effects. Moreover, therapeutic vaccination was shown to reduce
      allergic symptoms and T-cell activation in the spleen. CONCLUSION: The rflaA:OVA
      fusion protein showed strong TLR-mediated immunomodulating capacities probably
      attributed by the proximity of adjuvant and allergen, leading to the prevention
      of intestinal allergy in a murine disease model. Therefore recombinant
      flaA:allergen fusion proteins are promising vaccine candidates for intervention
      in patients with IgE-mediated allergy.

PMID- 21872304
TI  - Correlation of specific IgE to shrimp with cockroach and dust mite exposure and
      sensitization in an inner-city population.
AB  - BACKGROUND: Studies have demonstrated that IgE-binding cross-reactive epitopes
      between shrimp, cockroach, and house dust mite tropomyosins can account for the
      presence of detectable IgE to shrimp in patients with cockroach and dust mite
      allergies. OBJECTIVE: We investigated the correlation between IgE-mediated
      sensitization to shrimp, cockroach, and dust mite in relation to allergen
      exposure in inner-city children. METHODS: Five hundred four serum samples from
      the National Cooperative Inner-City Asthma Study were evaluated for specific IgE
      to shrimp, and the results were compared with specific IgE to cockroach
      (Blattella germanica) and dust mite (Dermatophagoides farinae). Associations
      between IgE sensitization to these allergens and environmental exposures were
      determined. RESULTS: There was a strong positive correlation between shrimp,
      cockroach, and dust mite IgE levels. High exposure to cockroach (B germanica) in
      the home, particularly in the bedroom and television room, was significantly
      correlated with higher shrimp and cockroach IgE levels. In contrast, high
      exposure to dust mite in the home was highly correlated with IgE levels to D
      farinae but not with shrimp IgE levels. There is a synergistic relationship
      between cockroach IgE levels and exposure in predicting shrimp IgE levels.
      CONCLUSIONS: For children with evidence of IgE-mediated sensitization to
      cockroach and shrimp, having high exposure to cockroach in the home can
      contribute to higher shrimp IgE levels, which might not correlate with clinical
      reactivity. Further patient evaluations with clinical histories of shrimp
      exposure and reactions, as well as oral food challenges, would have to be
      performed to confirm these findings.

PMID- 21872306
TI  - Bluetongue virus serotype 8: abortion and transplacental transmission in cattle
      in the Burgundy region, France, 2008-2009.
AB  - During the incursion of bluetongue virus (BTV) serotype 8 in France in 2007, an
      increase in the number of abortions in cattle was observed, but the cause was not
      clearly established. A survey of all the reported cases of abortion in cattle
      from November 2008 to April 2009 was conducted in the Nievre district (Burgundy
      region) to determine the percentage of abortions as a result of BTV-8 and to
      study factors that could have played a role in BTV-8 transplacental transmission.
      BTV-8 was present in 16% of the fetuses or newborn calves that died within 48 h,
      from 780 dams. Dams inseminated before the BTV epizootic peak recorded from July
      to September 2008 were more likely to have BTV-positive abortions (OR=5.7,
      P<0.001) and those vaccinated in May or June 2008 were less likely to have BTV
      positive abortions (OR=0.3, P=0.01 and OR=0.4, P=0.001, respectively). The
      gestational month was not a predictor of BTV abortion. In blood or spleen,
      fetuses/calves from RT-PCR-positive dams had significantly higher RNA
      concentrations than fetuses/calves from RT-PCR-negative dams. Of the 128 dams
      that had BTV-positive fetuses or calves, 60% were RT-PCR-negative. BTV-8-positive
      fetuses/calves were significantly more frequent (n=42 vs n=21, P=0.082) amongst
      those showing clinical signs or lesions suggestive of cerebral damage.

PMID- 21872307
TI  - Effect of early postpartum PGF2alpha treatment on reproductive performance in
      dairy cows with calving and puerperal traits.
AB  - The objective of this study was to evaluate the effects of early postpartum PGF
      two alpha treatment on reproductive performance in dairy cows with calving and
      puerperal traits. A total of 363 Holstein cows (128 primiparous and 235
      multiparous) were selected based on the presence of at least one of calving and
      puerperal traits (dystocia, retained placenta, twin, abortion, and postpartum
      uterine infections) and were assigned to two groups (treatment and control)
      irrespective of presence or absence of luteal tissue. Cows in the treatment group
      were treated twice with 25 mg dinoprost 8 h apart on day 20 postpartum, and for
      the control group saline placebo was administered. As it was speculated that the
      timing of a second dose would mimic the release of endogenous PGF2alpha from the
      uterus, our hypothesis was that two doses of PGF2alpha 8 h apart may increase the
      duration of elevated plasma prostaglandin F2alpha metabolite concentration in
      these cows. Recorded reproductive variables included days to first estrus, days
      to first AI, first service conception rate, pregnancy by 150 days in milk,
      service per conception, open days, and the percentage of repeat breeder animals.
      The data were analyzed using SPSS (Version 15) (IBM North America, New York, NY,
      USA) and Minitab (Version 14) (Minitab, State College, PA, USA). Although early
      postpartum PGF2alpha treatment had no effect on days to first estrus (36.7 days
      vs. 34.9 days, P = 0.056) and days to first AI (70.5 days vs. 72.2 days, P =
      0.537), it increased first service conception rate (47.1% vs. 27.6%, P < 0.001);
      and this was more remarkable in primiparous cows (64.7% vs. 25%, P < 0.001).
      PGF2alpha treatment reduced the mean service per conception (1.92 vs. 2.72, P <
      0.001) and the mean open days (112 days vs. 144 days, P < 0.001), and increased
      pregnancy by 150 days in milk (DIM) (80% vs. 66%, P = 0.004). The prevalence of
      repeat breeder syndrome in cows with calving and puerperal traits was reduced by
      PGF2alpha treatment (10% vs. 29.8%, P < 0.001). In conclusion, treatment of cows
      with calving and puerperal traits twice with a luteolytic dose of PGF2alpha 8 h
      apart on Day 20 postpartum improved reproductive performance and reduced the
      prevalence of repeat breeder syndrome.

PMID- 21872308
TI  - Evaluation of zebrafish (Danio rerio) PGCs viability and DNA damage using
      different cryopreservation protocols.
AB  - Cryopreservation of primordial germ cells (PGCs) is a better alternative for the
      conservation of the diploid genome in fish until embryo cryopreservation is
      achieved. A good cryopreservation protocol must guarantee high survival rates but
      also absence of genetic damage. In this study, a cell toxicity test using several
      internal and external cryoprotectants was carried out. The best combination of
      cryoprotectants (DMSO 5 mol/L, ethylene glicol (EG) 1 mol/L, polyvinyl
      pyrrolidone (PVP) 4%) was used with and without antifreeze proteins (AFPs) at two
      different concentrations (10 mg/mL and 20 mg/mL) for cryopreservation trials.
      Different cryopreservation methods were used with single PGCs, genital ridges,
      and whole zebrafish embryos using cryovials, 0.5 mL straws, microcapsules, and
      microdrops. All embryos were obtained from the vasa EGFP zf45 transgenic line and
      viability was evaluated using trypan blue. High cell viability rates after
      cryopreservation in 0.5 mL straws were obtained (around 90%) and a decrease in
      viability was only observed when cells were cryopreserved in microcapsules and
      when AFP at 20 mg/mL was added to the freezing media. Genetic damage was
      determined by comet assay and was compared in cells cryopreserved in 0.5 mL
      straws and microcapsules (lowest viability rate). There were significantly more
      DNA strand breaks after cryopreservation in the cells cryopreserved without
      cryoprotectants and in those cryopreserved in microcapsules. Genetic damage in
      the cells cryopreserved with cryoprotectants in 0.5 mL straws was similar to
      fresh control samples, regardless of the concentration of AFP used. The decrease
      in PGC viability with the addition of AFP 20 mg/mL did not correlate with an
      increase in DNA damage. This study reported a successful method for zebrafish PGC
      cryopreservation that not only guarantees high cell survival but also the absence
      of DNA damage.

PMID- 21872309
TI  - Boar seminal plasma or hen's egg yolk decrease the in-vitro chemotactic and
      phagocytotic activities of neutrophils when co-incubated with boar or bull sperm.
AB  - The objective was to determine the effects of boar seminal plasma and hen's egg
      yolk on chemotaxis and phagocytosis of porcine and bovine polymorphonuclear
      neutrophils (PMNs) in vitro. Chemotactic activity of PMNs was determined
      following culture for 90 min in a blind well chamber. Phagocytosis was assayed
      after co-culture of PMNs with sperm for 60 min. In the presence of >=5% boar
      seminal plasma, chemotactic activity of PMNs was reduced (P<0.05) in both pigs
      (from 1126.1 to 934.2-1009.1 cells/mm2) and in cows (from 1067.1 to 768.9-800.0
      cells/mm2). Furthermore, >=5% boar seminal plasma reduced (P<0.05) leukocyte
      phagocytosis in pigs (26.2-32.1%) and cows (27.2-30.0%) compared to controls
      (41.7 and 42.1%, respectively). Although 20% hen's egg yolk increased (P<0.05)
      chemotactic activity of PMNs in pigs (from 790.4 to 1006.1 cells/mm2) and cows
      (from 789.9 to 953.5 cells/mm2), egg yolk increased (P<0.05) phagocytotic
      activity of porcine PMNs (from 24.3 to 33.8%), but not the activity of bovine
      PMNs (15.1 vs 15.8% in controls). Boar seminal plasma and caffeine reduced
      (P<0.05) the egg yolk-induced increase in chemotaxis in both species (from 988.6
      to 795.2 or 813.2 cells/mm2 in pigs and from 953.5 to 779.4 or 833.8 cells/mm2 in
      cows), and phagocytotic activities of PMN (from 33.8% to 15.2 or 13.3%) only in
      pigs (but not in cows; 11.2-15.1%). In conclusion, hen's egg yolk increased
      chemotactic activity of PMNs in both pigs and cows, whereas egg yolk increased
      only phagocytosis of PMNs in pigs, but not in cows. Even in the presence of egg
      yolk, boar seminal plasma and caffeine significantly reduced chemotactic activity
      of PMNs in pigs and cows, and phagocytotic activity of porcine PMNs.

PMID- 21872310
TI  - Ovum pick-up and in vitro embryo production (OPU-IVEP) in Mediterranean Italian
      buffalo performed in different seasons.
AB  - This study was designed to evaluate the effect of season on in vivo oocyte
      recovery and embryo production in Mediterranean Italian buffalo (Bubalus
      bubalis). For this purpose repeated transvaginal ultrasound-guided ovum pick up
      (OPU) was conducted twice a week throughout autumn, mid-winter (transitional
      period) and spring-summer. The number and size of follicles was determined before
      puncture. The recovered oocytes were first classified in morphological categories
      and then used for in vitro embryo production (IVEP) according to standard
      procedures. The mean number of total follicles observed per session did not
      differ among the three periods we examined (on average 4.6). Although season did
      not considerably affect the number of oocytes recovered (on average
      2.3/buffalo/session), the number of degenerated and abnormally expanded oocytes
      increased during autumn. Furthermore, the percentage of abnormally expanded
      oocytes significantly increased during autumn (6.1%) compared with both the
      transitional period and spring-summer (1.9 and 2.3%, respectively).
      Interestingly, the embryo output we recorded at day 7, in terms of tight morulae
      blastocysts was higher in autumn (30.9%) compared to the other two periods (13.3%
      and 10.3%, respectively, in spring-summer and in the transitional period;
      P<0.01). The results of this trial demonstrated that the morphological features
      of the oocytes did not vary substantially among the considered periods, with the
      exception of degenerated and abnormally expanded oocytes. On the other hand, the
      oocyte developmental competence improved in autumn compared to spring-summer and
      the transitional period. This datum reflects buffalo reproductive pattern
      expressed in vivo at Italian latitudes.

PMID- 21872311
TI  - Changes in plasma concentrations of insulin-like peptide 3 and testosterone from
      birth to pubertal age in beef bulls.
AB  - The objectives were to: (1) develop an enzyme immunoassay (EIA) for insulin-like
      peptide 3 (INSL3) or relaxin-like factor (RLF) in bovine plasma; (2) investigate
      changes of plasma INSL3 concentrations from birth to pubertal age of beef bulls;
      and (3) compare changes in plasma concentrations of INSL3, testosterone, and LH.
      Plasma samples were collected from beef bull calves (n = 15) at birth (0 d) and
      at 28, 56, and 84 d after birth. Furthermore, in beef bulls around pubertal age
      (n = 26; age range 3 to 22 mo), plasma samples were collected at 1 to 4 mo
      intervals. Plasma INSL3 concentrations increased (P < 0.05) from 0 to 28, 28 to
      56, and from 56 to 84 d of age. Plasma testosterone concentrations increased (P <
      0.001) from 0 to 28 d, and from 28 to 56 d, but did not change from 56 to 84 d.
      For bulls around pubertal age, plasma INSL3 concentrations did not change from
      the prepubertal phase (3 to 6 mo) to the early pubertal phase (6 to 12 mo), but
      increased (P < 0.05) from the early to late pubertal phases (12 to 18 mo), and
      from the late pubertal to postpubertal phases (18 to 22 mo). Plasma testosterone
      concentrations increased from the prepubertal to early pubertal phases (P <
      0.001), but did not change thereafter. Plasma LH concentrations did not change
      from 0 d to 84 d, but decreased (P < 0.001) from prepubertal to early pubertal
      phase, with no significant change thereafter. Plasma INSL3 concentrations
      increased during the first 3 mo of life and throughout the pubertal age in beef
      bulls. There were similar dynamic patterns for INSL3 and testosterone during the
      first 3 mo of life, but patterns subsequently diverged in bulls around pubertal
      ages.

PMID- 21872312
TI  - Characteristics of donkey spermatozoa along the length of the epididymis.
AB  - In mammals, the epididymis has numerous interrelated functions including
      absorptive and secretory activity that affect luminal environment and cell
      membrane, and the maturation and storage of sperm. Spermatozoa acquire their
      motility and fertilizing ability during their passage through the epididymis and
      the motility of epididymal spermatozoa should be a balance between the maturation
      of flagellum and the inhibition of the flagellar machinery. In this study
      maturational change in sperm characteristics were evaluated in the epididymis of
      donkey. Spermatozoa collected from four portions of the epididymis (head, cranial
      corpus, caudal corpus, tail) were compared before and after ejaculation for
      viability, mitochondrial activity, kinetic parameters, and morphology. A
      significant increase in the mitochondrial activity along the epididymis was
      reported, suggesting a possible involvement in the motion mechanism. This should
      be corroborated by the significant correlation between mitochondrial activity and
      the total and progressive motility and the increase in velocities of spermatozoa
      recorded by computer-assisted sperm analysis. The percentage of most of the
      abnormal spermatozoa were similar in all tracts, with a great variability between
      jackasses. Only the bent midpiece percentage decreased significantly along
      epididymis. A significant increase in the percentage of distal cytoplasmic
      droplets (DCD), and a simultaneous decrease in the proximal cytoplasmic droplets
      (PCD), was found. The DCD fell down after ejaculation suggesting the late loss of
      the cytoplasmic residual (DCD) in the donkey, as hypothesized in the stallion.
      Because the prevalence of PCD were similar in both tail epididymal and ejaculated
      spermatozoa, a defect of the maturative process in the PCD sperm should be
      speculated.

PMID- 21872313
TI  - Progesterone enhances in vitro development of bovine embryos.
AB  - Increased pregnancy rates in cattle given progesterone (P4) prior to 5 d after
      breeding have recently been reported. The objective was to determine if this
      increase in pregnancy rate could be attributed to a direct positive effect of P4
      on the developing embryo. In Experiment 1, 280 bovine oocytes were inseminated in
      vitro and at Day 3 (insemination=Day 0), good quality 8 cell embryos (n=206) were
      randomly allocated to be cultured in either CR1aa+serum with 0 or ~15 ng/mL
      (n=102 and n=104, respectively). In Experiment 2, 881 bovine oocytes were used;
      on Day 3, good quality 8 cell embryos (n=511) were randomly allocated to either
      the control (CR1aa+FCS, n=168), vehicle (CR1aa+FCS+ethanol, n=170), or P4
      treatment (CR1aa+FCS+~15 ng/mL P4 in ethanol, n=173). On Day 7, in both
      experiments, there were increased numbers of blastocysts developing in the P4
      group (Experiment 1, 59% and Experiment 2, 71%) compared to the vehicle
      (Experiment 2, 53%) or control (40 and 62% in Experiments 1 and 2, respectively).
      The addition of P4 (8%) stimulated the rate of embryo development (early
      blastocysts or more advanced stages on Day 6) compared to vehicle (3%) and
      control (0%) and the P4 group had more hatched or hatching blastocysts (33%) on
      Day 9 compared to the control or vehicle group (21 or 22%). Additionally, the P4
      group had greater embryo diameter and significantly more Grade 1 blastocysts on
      Day 7. In conclusion, P4 had a direct, positive effect on developing bovine
      embryos cultured in vitro.

PMID- 21872314
TI  - Differential expression of porcine sperm microRNAs and their association with
      sperm morphology and motility.
AB  - MicroRNAs (miRNAs) are involved in nearly every biological process examined to
      date, but little is known of the identity or function of miRNA in sperm cells or
      their potential involvement in spermatogenesis. The objective was to identify
      differences in miRNA expression between normal porcine sperm samples and those
      exhibiting high percentages of morphological abnormalities or low motility.
      Quantitative RT-PCR was performed on sperm RNA to compare expression levels of 10
      specific miRNAs that are predicted to target genes that code for proteins
      involved in spermatogenesis, sperm structure, motility, or metabolism. There were
      increases in the expression of four miRNAs, let-7a, -7d, -7e, and miR-22, in the
      abnormal group (P < 0.05), whereas miR-15b was decreased compared to controls (P
      < 0.05). Two miRNAs, let-7d and let-7e, were increased in the low motility group
      when compared to controls (P < 0.05). Bioinformatic analyses revealed that
      messenger RNA targets of the differentially expressed miRNAs encode proteins
      previously described to play roles in sperm function. Although the precise role
      of miRNA in sperm remains to be determined, their changes as associated with
      morphology and motility signify a critical biological function. Perhaps they are
      remnants of spermatogenesis, stored for a later role in fertilization, or are
      delivered to the oocyte to influence early embryonic development. Although there
      is no single cause of male infertility, the identification of miRNAs associated
      with sperm motility, structural integrity, or metabolism could lead to the
      development of a microarray or real time-based diagnostic assay to provide an
      assessment of male fertility status.

PMID- 21872315
TI  - Breed and experience effect on the sexual behaviors of Damascus and Egyptian
      Nubian goat bucks.
AB  - This study compares the sexual behaviors of bucks from two pure breeds of goats,
      Damascus and Egyptian-Nubian (Zaraibi), and assesses their relationships with the
      pregnancy and kidding rates of their inseminated does. Twenty-three bucks (12
      Damascus and 11 Egyptian-Nubian bucks) were used in this study. These bucks were
      either in their first season of service (N =12, with an average age of 1.51
      years) or had been previously used in service for several seasons (N = 11, with
      an average age of 3.34 years). Buck service behaviors toward estrous does were
      continuously recorded for 30 minutes from the moment of appearance of the doe.
      Egyptian-Nubian bucks were highly sexually active with estrous does in comparison
      with Damascus bucks. They required less time to mount and ejaculate for the first
      (P < 0.04) and second times (P < 0.0002) and tended to sniff, nudge and vocalize
      more frequently than Damascus bucks. In addition, Egyptian-Nubian bucks had more
      ejaculations and a higher mating efficiency (27.48% vs. 10.21%, P < 0.001), and
      their inseminated does had a higher pregnancy rate and larger litter sizes.
      Regarding the effect of experience, the data revealed a limited influence. No
      significant differences in sexual behavior were recorded between younger and
      older bucks. Conversely, pregnancy, kidding rates, and litter size were not
      influenced by the total number of ejaculations. From these results, it can be
      concluded that there were sexual behavior differences as a function of breed
      between Damascus and Egyptian-Nubian bucks and that experience had little impact
      in this study.

PMID- 21872316
TI  - Additional value of computer assisted semen analysis (CASA) compared to
      conventional motility assessments in pig artificial insemination.
AB  - In order to obtain a more standardised semen motility evaluation, Varkens KI
      Nederland has introduced a computer assisted semen analysis (CASA) system in all
      their pig AI laboratories. The repeatability of CASA was enhanced by
      standardising for: 1) an optimal sample temperature (39  degrees C); 2) an
      optimal dilution factor; 3) optimal mixing of semen and dilution buffer by using
      mechanical mixing; 4) the slide chamber depth, and together with the previous
      points; 5) the optimal training of technicians working with the CASA system; and
      6) the use of a standard operating procedure (SOP). Once laboratory technicians
      were trained in using this SOP, they achieved a coefficient of variation of < 5%
      which was superior to the variation found when the SOP was not strictly used.
      Microscopic semen motility assessments by eye were subjective and not comparable
      to the data obtained by standardised CASA. CASA results are preferable as
      accurate continuous motility dates are generated rather than discrimination
      motility percentage increments of 10% motility as with motility estimation by
      laboratory technicians. The higher variability of sperm motility found with CASA
      and the continuous motility values allow better analysis of the relationship
      between semen motility characteristics and fertilising capacity. The benefits of
      standardised CASA for AI is discussed both with respect to estimate the correct
      dilution factor of the ejaculate for the production of artificial insemination
      (AI) doses (critical for reducing the number of sperm per AI doses) and thus to
      get more reliable fertility data from these AI doses in return.

PMID- 21872317
TI  - Effects of Hoechst 33342 staining and ultraviolet irradiation on the
      developmental competence of in vitro-matured porcine oocytes.
AB  - Hoechst 33342 (H342) in combination with ultraviolet (UV) irradiation is
      frequently used to assist the enucleation of porcine oocytes in somatic cell
      nuclear transfer programs. This work evaluated the effects of H342 (5 MUg/mL for
      12 min) staining and/or exposure to UV irradiation on fertilisability and
      developmental capacity of porcine oocytes matured in vitro. In Experiment 1, a
      total of 1388 mature oocytes were distributed in the following groups: Group 1:
      oocytes without treatment (Control), Group 2: oocytes stained with H342, Group 3:
      oocytes stained with H342 and UV irradiated for 30 sec, and Group 4: oocytes UV
      irradiated for 30 sec. Oocytes from each group were exposed to thawed spermatozoa
      and cultured for 18 h to assess fertilization parameters or for 7 d to evaluate
      embryo development. Sperm penetration (P < 0.001) and monospermy (P < 0.04) were
      lower in oocytes exposed to H342/UV (80.7 +/- 4.5% and 30.7 +/- 5.4%,
      respectively) than in oocytes from the control group (94.9 +/- 4.3 and 50.0 +/-
      4.9, respectively). The oocytes exposed to H342/UV showed lower (P < 0.001)
      cleavage (49.8 +/- 2.9%) and blastocyst (7.7 +/- 2.9%) rates than oocytes from
      the other groups (range: 73.8 +/- 2.9% to 77.7 +/- 2.9% and 22.3 +/- 2.9% to 30.9
      +/- 3.0%, respectively). Experiment 2 was designed to evaluate the effect of
      shorter UV irradiation (5 sec). A total of 1835 mature oocytes were separated
      into the same groups as those of Experiment 1. The fertilization parameters and
      the cleavage rates were not influenced by the different treatments. However, the
      oocytes exposed to H342 and UV irradiation for 5 sec showed a lower (P < 0.02)
      rate of blastocyst formation (15.2 +/- 4.5%) than the oocytes from other groups
      (range: 26.1 +/- 4.5% to 30.7 +/- 4.5%). In conclusion, our results demonstrate
      that the combination of H342 staining with UV irradiation has a clear deleterious
      effect on the developmental ability of oocytes, with the effects being more
      intense with increased exposure to UV irradiation.

PMID- 21872318
TI  - Induction of fertile oestrus in the bitch using Deslorelin, a GnRH agonist.
AB  - Oestrus induction in various canine breeds was attempted in 32 bitches. A group
      of 8 bitches were treated 80-160 d following their previous oestrus (G1) whereas
      a second group of 24 bitches (G2) were implanted 200-590 d following their
      previous oestrus. The treatment for each bitch consisted in one Deslorelin
      implant (Suprelorin(r) 4,7 mg, Virbac, France), inserted subcutaneously in the
      post-umbilical region. Ovulation, pregnancy rate and litter size were recorded.
      All bitches came in heat 4.3 +/- 1.4 d after implantation (2-7 d). Ovulation was
      reported in 62.5% in G1 and 87.5% in G2. One bitch refused mating and since no AI
      was performed, she was not considered for further analysis. Pregnancy was
      obtained in 25% in G1 versus 78.3% in G2. Mean litter size was 6.7 +/- 3.5
      puppies (1-14). Luteal failure was suspected in 3 bitches, two that remained non
      pregnant and one which aborted 58 d post-ovulation since the owner refused
      progesterone supplementation. Deslorelin implants can therefore be considered as
      a valuable alternative to induce fertile oestrus in bitches in anoestrus. Follow
      up of the luteal phase is recommended, since some bitches might encounter luteal
      failure.

PMID- 21872319
TI  - Effect of restraint stress on plasma concentrations of cortisol, progesterone and
      pregnancy associated-glycoprotein-1 in pregnant heifers during late embryonic
      development.
AB  - The aim of the present study was to evaluate the effect of restraint stress,
      which is commonly practised in the field, on plasma concentrations of cortisol,
      progesterone (P4) and bovine pregnancy-associated glycoprotein-1 (boPAG-1) in
      pregnant heifers between Days 30 to 40 of gestation. Twelve Holstein-Friesian
      heifers between Days 30 (Day 0 of experiment) and 40 (Day 10 of experiment) of
      pregnancy in a Hungarian dairy farm were used in the present study. The heifers
      were exposed to an acute stressor consisting of immobilisation (restraint stress)
      in a crush for 2 h (Group 1, n = 6) on Day 2 (Hour 48) and for 2 * 2 h (Group 2,
      n = 6) on Days 2 and 3 (Hour 72) of the experiment. Transrectal ultrasonography
      (7.5 MHz linear-array rectal transducer) was performed daily from Day 0 to Day 10
      of the experiment to detect embryonic heartbeat or the fate of the conceptus.
      Blood samples were withdrawn before each ultrasonographic examination. Additional
      blood samples were withdrawn by 1 and 2 h (at Hours 49 and 50 in Groups 1 and 2
      and Hours 73 and 74 in Group 2) of the onset of applying the stressor. Plasma
      cortisol, P4 and boPAG-1 concentrations were measured by radioimmunoassay. Acute
      restraint stress significantly (P < 0.001) increased the plasma cortisol level in
      pregnant heifers at 1 h of the exposure to the stressor at Days 2 (48 h) and 3
      (72 h) of the experiment. On the other hand, the restraint stress did not affect
      the concentration of P4 and boPAG-1 concentrations in both groups. In conclusion,
      restraint stress for 2 h during early pregnancy in heifers increased blood
      cortisol, but it did not affect the concentrations of P4 and boPAG-1 between Days
      30 to 40 of gestation.

PMID- 21872320
TI  - Assessment of canine ovaries autografted to various body sites.
AB  - The influence of graft site on the survival of canine follicles and oocytes after
      autografting was investigated. Hemi-ovaries were autografted to three locations
      (quadriceps femoris muscle fascia, kidney capsule, and gastrosplenic ligament),
      and grafted ovaries were recovered (under anesthesia) 28 to 31 d after
      transplantation. The grafted hemi-ovaries were bisected: one-quarter ovary was
      used for histological assessment and another quarter for evaluation of oocyte
      viability. As controls, the remaining fresh hemi-ovaries were used to assess the
      viability of follicles and oocytes in non-transplanted ovaries. Most follicles in
      the histological sections of the grafts were classified as primordial or primary
      follicles. Antral follicles were not observed in the grafts, irrespective of the
      graft site. The percentages of viable follicles in the sections from control
      ovaries, and the ovaries grafted to the kidney capsule, the quadriceps femoris
      muscle fascia, and the gastrosplenic ligament were 17.4, 22.9, 18.3, and 32.4%,
      respectively. A total of 12 oocytes was recovered from the 15 hemi-ovaries
      grafted in five bitches, of which five (41.7%) oocytes from the ovaries grafted
      to the quadriceps femoris muscle fascia and the kidney capsule were cultured for
      assessment of meiotic competence. Three oocytes were viable but remained in the
      germinal vesicle stage after 72 h of maturation culture. The quadriceps femoris
      muscle fascia might be useful for grafting like the kidney capsule, but
      improvement of follicle survival and meiotic competence of oocytes in the grafts
      is necessary.

PMID- 21872321
TI  - Temporal relationships of a pulse of prolactin (PRL) to a pulse of a metabolite
      of PGF2alpha in mares.
AB  - Hourly blood samples were collected from 10 mares during 24 h of each of the
      preluteolytic, luteolytic, and postluteolytic periods. The autocorrelation
      function of the R program was used to detect pulse rhythmicity, and the intra
      assay CV was used to locate and characterize pulses of prolactin (PRL) and a
      metabolite of prostaglandin F2alpha (PGFM). Rhythmicity of PRL and PGFM
      concentrations was detected in 67% and 89% of mares, respectively. Combined for
      the three periods (no difference among periods), the PRL pulses were 5.2+/-0.4 h
      (mean+/-SEM) at the base, 7.5+/-1.5 h between nadirs of adjacent pulses, and
      12.3+/-1.5 h from peak to peak. The peaks of PRL pulses were greater (P<0.05)
      during the luteolytic period (46+/-14 ng/mL) and postluteolytic period (52+/-15
      ng/mL) than during the preluteolytic period (17+/-3 ng/mL). Concentrations of PRL
      during hours of a PGFM pulse were different (P<0.003) within the luteolytic
      period and postluteolytic period and were greatest at the PGFM peak; PRL
      concentrations during a PGFM pulse were not different during the preluteolytic
      period. The frequency of the peak of PRL and PGFM pulses occurring at the same
      hour (synchrony) was greater for the luteolytic period (65%, P<0.01) and
      postluteolytic period (50%, P<0.001) than for the preluteolytic period (17%).
      This is the first report in mares on characterization and rhythmicity of PRL
      pulses, synchrony between PRL and PGFM pulses, and greater PRL activity during
      the luteolytic and postluteolytic periods than during the preluteolytic period.

PMID- 21872322
TI  - Bilateral spontaneous anterior dislocation of crystalline lens in an infant.

PMID- 21872323
TI  - The effect of CdSe-ZnS quantum dots on calcium currents and catecholamine
      secretion in mouse chromaffin cells.
AB  - Semiconductor nanocrystal quantum dots (QDs) possess an enormous potential of
      applications in nanomedicine, drug delivery and bioimaging which derives from
      their unique photoemission and photostability characteristics. In spite of this,
      however, their interactions with biological systems and impact on human health
      are still largely unknown. Here we used neurosecretory mouse chromaffin cells of
      the adrenal gland for testing the effects of CdSe-ZnS core-shell quantum dots (5
      36 nM) on Ca(2+) channels functionality and Ca(2+)-dependent neurosecretion.
      Prolonged exposure (24 h) to commonly used concentrations of CdSe-ZnS QDs (>=16
      nM) showed that the semiconductor nanocrystal is effectively internalized into
      the cells without affecting cell integrity (no changes of membrane resistance and
      cell capacitance). QDs reduced the size of Ca(2+) currents by ~28% in a voltage
      independent manner without affecting channel gating. Correspondingly,
      depolarization-evoked exocytosis, measured at +10 mV, where Ca(2+) currents are
      maximal, was reduced by 29%. CdSe-ZnS QDs reduced the size of the readily
      releasable pool (RRP) of secretory vesicles by 32%, the frequency of release by
      33% and the overall quantity of released catecholamines by 61%, as measured by
      carbon fibers amperometry. In addition, the Ca(2+)-dependence of exocytosis was
      reduced, whereas the catecholamine content of single granules, as well as the
      kinetics of release, remained unaltered. These data suggest that exposure to CdSe
      ZnS QDs impairs Ca(2+) influx and severely interferes with the functionality of
      the exocytotic machinery, compromising the overall catecholamine supply from
      chromaffin cells.

PMID- 21872324
TI  - On the mechanism of poly(methacrylic acid -co- methyl methacrylate)-induced
      angiogenesis: gene expression analysis of dTHP-1 cells.
AB  - Identifying the critical molecules associated with "biocompatibility" is a grand
      challenge. Poly(methacrylic acid -co- methyl methacrylate) (MAA) beads improve
      wound closure and wound vascularity in vivo, but the mechanism of this phenomenon
      is unknown. We used quantitative real-time PCR to identify the subtle changes in
      the expression of a small selection of molecules involved in wound healing and
      angiogenesis in a macrophage-like cell (dTHP-1) treated with the MAA beads (45
      mol% methacrylic acid). MAA beads decreased the expression of osteopontin (OPN)
      compared to poly(methyl methacrylate) (PMMA) and untreated cells, and increased
      the expression of IL-1beta, IL-6 and TNF-alpha over the 24-96 h of the
      experiment. Interestingly, molecules associated with angiogenesis, such as bFGF,
      CXCL12, HIF-1alpha, PDGF-B, TGF-beta and VEGF, were not significantly affected by
      MAA beads over the course of the study. MAA beads also increased the gene
      expression of OPN in HUVEC compared to untreated cells, while PMMA beads did not.
      MAA beads modified the phenotype (gene expression) of dTHP-1 cells in a subtle
      yet distinct manner that was different than PMMA. It remains to connect the
      changes in OPN in dTHP-1 (and HUVEC) and other molecules to the enhanced
      vascularity seen in vivo with this polymer.

PMID- 21872325
TI  - The role of plasma proteins in cell adhesion to PEG surface-density-gradient
      modified titanium oxide.
AB  - Surface-density gradients of poly(ethylene glycol) (PEG) were fabricated, in
      order to carry out a systematic study of the influence of PEG chain density on
      protein adsorption and cell-adhesion behavior, as well as the correlation between
      them. Gradients with a linear change in coverage of the polycationic polymer
      Poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG) were prepared on titanium
      dioxide surfaces by a controlled dipping process and characterized by variable
      angle spectroscopic ellipsometry and fluorescence microscopy. The adsorption
      behavior of single proteins (fibrinogen and albumin) generally correlated with
      semiempirical geometric models, illustrating the effect of the PEG-chain surface
      distribution on the inhibition of protein adsorption. Distinct differences could
      be observed between individual adsorbing proteins, attributable to their mode of
      surface attachment. The single and competitive adsorption of protein solutions
      containing albumin and fibrinogen was then investigated by fluorescence
      microscopy, indicating a larger amount of fibrinogen adsorption compared with
      albumin adsorption (in minutes to hours) along the entire PLL-g-PEG gradient
      samples. To further elucidate the underlying mechanism of cell adhesion and
      spreading as a function of PEG coverage and the potential involvement of
      integrins, cell-adhesion assays were carried out with human foreskin fibroblasts
      (hFF). The use of surface-gradient samples demonstrated the importance for
      protein adsorption of PEG conformation, the amount of exposed titanium dioxide
      surface area (and its distribution), and the structure and chemistry of the
      proteins involved. Correspondingly the influence of these factors on cell
      adhesion could be directly observed, and insights gained into the roles of both
      nonspecific binding and specific integrin binding in cell adhesion.

PMID- 21872327
TI  - Pathways of macrophage apoptosis within the interface membrane in aseptic
      loosening of prostheses.
AB  - Aseptic loosening is a major cause of failure of total hip arthroplasty (THA).
      Macrophage apoptosis in interface membrane has been proved to play an important
      role in the pathogenesis of aseptic loosening. The purpose of current study was
      to identify the apoptotic mechanism of macrophages in the interface membrane of
      aseptic loosening. We collected periprosthetic interface membrane from 23
      patients undergoing the revision operations for aseptic loosening of hip joint
      prostheses. To serve as the control group, samples of capsule were collected from
      18 patients undergoing the primary hip arthroplasties for osteoarthritis (OA).
      The ultrastructure of interface membrane was examined by transmission electron
      microscopy (TEM), and in situ apoptotic macrophage identification was performed
      by TUNEL staining. Furthermore, using immunohistochemical methods we investigated
      the expression of some apoptosis-related markers such as inducible nitric oxide
      synthase (iNOS), peroxynitrite (ONOO(-)), cleaved caspase-3/4/8/9, cytochrome c,
      glucose regulated protein 78 (GRP78), and growth arrest and DNA damage-inducible
      gene 153 (GADD153) in macrophages. These markers were regarded as apoptotic
      inducers or specific indicators of different apoptotic pathways such as death
      receptor pathway, mitochondrial pathway and endoplasmic reticulum (ER) stress
      pathway. TEM showed that a great deal of wear debris was phagocytosed by
      macrophages, which displayed morphological changes characteristic of apoptosis.
      The results of TUNEL staining demonstrated that there were more apoptotic
      macrophages in interface membrane. The expression levels of iNOS, ONOO(-),
      cleaved caspase-3/4/8/9, cytochrome c, GRP78 and GADD153 in macrophages in
      interface membrane were significantly higher than those in the control samples (p
      < 0.05). Our results suggest that death receptor pathway,
      mitochondria/cytochrosome c caspase-dependent pathway and ER stress pathway are
      involved in the process of macrophage apoptosis. A therapeutic target to modulate
      the apoptotic pathways in macrophages may be a strategy to prevent and treat
      aseptic loosening.

PMID- 21872326
TI  - The influence of elasticity and surface roughness on myogenic and osteogenic
      differentiation of cells on silk-elastin biomaterials.
AB  - The interactions of C2C12 myoblasts and human bone marrow stem cells (hMSCs) with
      silk-tropoelastin biomaterials, and the capacity of each to promote attachment,
      proliferation, and either myogenic- or osteogenic-differentiation were
      investigated. Temperature-controlled water vapor annealing was used to control
      beta-sheet crystal formation to generate insoluble silk-tropoelastin biomaterial
      matrices at defined ratios of the two proteins. These ratios controlled surface
      roughness and micro/nano-scale topological patterns, and elastic modulus,
      stiffness, yield stress, and tensile strength. A combination of low surface
      roughness and high stiffness in the silk-tropoelastin materials promoted
      proliferation and myogenic-differentiation of C2C12 cells. In contrast, high
      surface roughness with micro/nano-scale surface patterns was favored by hMSCs.
      Increasing the content of human tropoelastin in the silk-tropoelastin materials
      enhanced the proliferation and osteogenic-differentiation of hMSCs. We conclude
      that the silk-tropoelastin composition facilitates fine tuning of the growth and
      differentiation of these cells.

PMID- 21872328
TI  - Lysosomally cleavable peptide-containing polymersomes modified with anti-EGFR
      antibody for systemic cancer chemotherapy.
AB  - Polymersomes (Ps) based on a biodegradable and biocompatible block copolymer of
      methoxy poly(ethylene glycol) (mPEG) and poly(D,L-lactide) (PDLLA) in which
      apeptide sequence, Gly-Phe-Leu-Gly-Phe (GFLGF), was introduced in between the two
      blocks(mPEG-pep-PDLLA) were developed. The peptide linker is cleavable by the
      lysosomal enzymecathepsin B (Cath B). Ps containing the peptide linker (Ps(pep))
      with an average diameter of about 124 nm were prepared by injecting a THF
      solution of the block copolymer into DI water. The Ps had a membrane thickness of
      about 15 nm as determined by transmission electron microscopy (TEM). In order to
      investigate the enzymatic degradation of the Ps (pep), dynamic light scattering
      (DLS) measurements of Ps(pep) dispersions with different concentrations of Cath B
      at pH 5.5 and 7.4 were performed as a function of time. A gradual decrease in
      kilo counts per second (Kcps) of the Ps (pep) over 7 d was observed after
      incubation of the Ps (pep) dispersions with 5 units/ml of Cath B at pH 5.5 at 37 
      degrees C. The size distribution became also bimodal, indicating that aggregation
      and precipitation of Ps (pep) occurred by disintegration of the Ps (pep) as a
      result of cleavage of the peptide. The rate of disintegration of the Ps (pep) was
      depending on the concentration of Cath Band the pH. No changes by DLS were seen
      when the dispersions were incubated with the enzyme at pH 7.4. Acridine orange
      (AO) was encapsulated in Ps (pep)as a model drug and rapid release of AO
      triggered by Cath B degradation of Ps (pep) was observed at pH 5.5. Anti
      epidermal growth factor receptor (anti-EGFR) antibody (abEGFR) was immobilized on
      the surface of Ps(pep)in order to enhance the cellular uptake of Ps (pep).
      Fluorescein isothiocyanate labeled dextran (40,000 g/mol) (FD40) was incorporated
      in the Ps (pep) for the cell study and Ps either without peptide or antibody or
      without both peptide and antibody were used as negative controls. After 3 d
      exposure to SKBR3 cells, abEGFR-conjugated Ps (pep) (abEGFR-Ps (pep)) were
      directly bound to the membrane of the cells and were endocytosed more rapidly as
      compared to Ps (pep)without abEGFR. Intracellular release of FD40 from Ps (pep)
      was observed, suggesting that the peptide linker in Ps (pep) was cleaved in the
      lysosomal compartments of the cells leading to Ps (pep) membrane disruption. An
      Alexa Fluor((r)) 488 labeled fragment of anti-mouse IgG (F(ab')(2)A) was also
      coupled to Ps (pep). Specific binding of the Ps (pep) coupled IgG (F(ab')(2)A)
      onto SKBR3 cells treated with primary mouse antibody was observed, whereas no
      binding was found with SKBR3 cells treated with goat antibody.

PMID- 21872329
TI  - Target specific hyaluronic acid-interferon alpha conjugate for the treatment of
      hepatitis C virus infection.
AB  - Interferon alpha (IFNalpha) conjugated with polyethylene glycol (PEG) has been
      widely used for the treatment of hepatitis C virus (HCV) infection as a once-a
      week injection formulation. However, the PEGylated IFNalpha has a low efficacy of
      ca. 39% and a side effect after repeated injections possibly due to the non
      specific delivery with PEGylation. In this work, target specific long-acting
      hyaluronic acid-interferon alpha (HA-IFNalpha) conjugate was successfully
      developed for the treatment of HCV infection. HA-IFNalpha conjugate was
      synthesized by coupling reaction between aldehyde modified HA and the N-terminal
      group of IFNalpha. The IFNalpha content could be controlled in the range of 2-9
      molecules per single HA chain with a bioconjugation efficiency higher than 95%.
      According to in vitro anti-proliferation assay using Daudi cells, HA-IFNalpha
      conjugate showed a comparable biological activity to PEG-Intron. In vivo real
      time bioimaging confirmed the target specific delivery of near-infrared
      fluorescence (NIRF) dye labeled HA-IFNalpha conjugate to the liver in mice. In
      addition, pharmacokinetic analysis revealed the enhanced residence time longer
      than 4 days. After tail-vein injection, HA-IFNalpha conjugate induced ca. 60%
      higher expression of 2',5'-oligoadenylate synthetase 1 (OAS 1) for innate immune
      responses to viral infection in the murine liver tissues than IFNalpha and PEG
      Intron.

PMID- 21872330
TI  - Myelodysplastic syndromes and bone marrow microenvironment.

PMID- 21872331
TI  - Residues of organochlorine pesticides (OCPs) in upper reach of the Huaihe River,
      East China.
AB  - Residues of HCHs and DDTs in surface water and suspended particulate matter (SPM)
      from upper reach of the Huaihe River, East China, were investigated. Levels of
      total HCHs (?HCH) and total DDTs (?DDT) in water detected by GC-ECD ranged from
      0.85 to 12.77 ng L-1 and from 3.54 to 33.59 ng L-1, respectively. According to
      European and America water quality guidelines, HCHs were within safe levels while
      DDT would pose adverse biological effects. Distribution of OCPs in water
      indicated that input of tributaries was important factor for the Huaihe River.
      For OCPs in SPM, concentrations varied from 1.01 to 25.22 ng g-1 for ?HCH and not
      detected to 4.74 ng g-1 for ?DDT. Compared with sediment quality guidelines, HCHs
      and DDTs might have an ecological risk. The main reason for OCPs residues in the
      Huaihe River was usage of lindane and technical DDT. Furthermore, composition of
      DDTs reflected fresh inputs of dicofol mixture in some sites.

PMID- 21872332
TI  - Toxicity of fluorotelomer carboxylic acids to the algae Pseudokirchneriella
      subcapitata and Chlorella vulgaris, and the amphipod Hyalella azteca.
AB  - Perfluorinated acids (PFAs) have elicited significant global regulatory and
      scientific concern due to their persistence and global pervasiveness. A source of
      PFAs in the environment is through degradation of fluorotelomer carboxylic acids
      (FTCAs) but little is known about the toxicity of these degradation products.
      Previous work found that FTCAs were two to three orders of magnitude more toxic
      to some freshwater invertebrates than their PFA counterparts and exhibited
      comparable chain-length-toxicity relationships. In this study, we investigated
      the toxicity of the 6:2, 8:2, and 10:2 saturated (FTsCA) and unsaturated (FTuCA)
      fluorotelomer carboxylic acids to two species of freshwater algae, Chlorella
      vulgaris and Pseudokirchneriella subcapitata, and the amphipod, Hyalella azteca.
      C. vulgaris was generally the most sensitive species, with EC50s of 26.2, 31.8,
      11.1, and 4.2 mg/L for the 6:2 FTsCA, 6:2 FTuCA, 8:2 FTuCA, and 10:2 FTsCA,
      respectively. H. azteca was most sensitive to the 8:2 FTsCA and 10:2 FTuCA, with
      LC50s of 5.1 and 3.7 mg/L. The toxicity of the FTCAs generally increased with
      increasing carbon chain length, and with saturation for most of the species
      tested, with the exception of P. subcapitata, which did not exhibit any trend.
      These observations agree with chain-length-toxicity relationships previously
      reported for the PFCAs and support the greater toxicity of the FTCAs compared to
      PFCAs. However, the toxicity values are approximately 1000-fold above those
      detected in the environment indicating negligible risk to aquatic invertebrates.

PMID- 21872333
TI  - Apoptotic cells enhance IL-10 and reduce IL-23 production in human dendritic
      cells treated with zymosan.
AB  - Contact of apoptotic cells (AC) with phagocytes tilts the balance of pro
      inflammatory and anti-inflammatory cytokines. To address the cell- and stimulus
      dependency of this mechanism, human monocyte-derived dendritic cells were treated
      with Jurkat AC in the presence and absence of different stimuli. AC reduced the
      production of IL-23 and enhanced the production of IL-10 elicited by zymosan, but
      they did not influence IL-12 p70 production nor did they modify the effect of
      LPS. Since formation of lipid bodies (LB) and PGE(2) production have been
      associated with IL-10 induction, the effect of PGE(2), the formation of LB, and
      the role of PPAR-gamma were assessed. Exogenous PGE(2) enhanced IL-10 expression,
      but no evidence of PGE(2) production elicited by AC was obtained. Inhibition of
      PPAR-gamma activity reduced the production of IL-10 both in the presence and in
      the absence of AC, but formation of LB in response to zymosan and AC was not
      observed. Notably, AC induced a transient nuclear translocation of both the CREB
      coactivator CRTC2/TORC2 and the homeodomain protein PBX1, which are involved in
      the CREB/HOX/PBX/MEIS transcription complex. These data show a selective effect
      of AC on the production of cytokines elicited by the fungal surrogate zymosan
      through the enhancement of CREB-dependent transcription.

PMID- 21872334
TI  - Does colocated care improve access to cardiometabolic screening for patients with
      serious mental illness?
AB  - OBJECTIVE: Individuals with serious mental illness (SMI; e.g., schizophrenia,
      bipolar disorder) experience disparities in mortality relative to the general
      population, mainly because of medical conditions (i.e., cardiometabolic
      disease).We assessed whether VA patients with SMI and receiving care from VA
      mental health facilities with colocated medical care were more likely to receive
      cardiometabolic risk assessments in accordance with clinical practice guidelines
      than patients from noncolocated facilities. METHODS: Patients with SMI identified
      prescribed second-generation antipsychotic medications in fiscal year (FY) 2007
      receiving care from VA mental health facilities completing the VA Mental Health
      Program Survey were included. VA administrative data were ascertained to assess
      receipt of the following tests every 6 months in FY 2007: body mass index (BMI),
      blood pressure, lipid profile and fasting glucose. RESULTS: Out of 40,600
      patients with SMI prescribed second-generation antipsychotics, 29% received all
      cardiometabolic tests (lipid, glucose, BMI and blood pressure). While 79% and 76%
      received blood pressure and BMI assessments, respectively, only 37% received a
      lipid test. Patients from colocated sites were more likely to receive all
      cardiometabolic tests (odds ratio=1.26, 95% confidence interval: 1.18-1.35,
      P<.001). CONCLUSIONS: Colocated general medical providers in mental health
      clinics are more likely to provide cardiometabolic assessments for patients with
      SMI prescribed second-generation antipsychotics.

PMID- 21872335
TI  - The effect of aripiprazole and quinagolide, a dopamine agonist, in a patient with
      symptomatic pituitary prolactinoma and chronic psychosis.
AB  - BACKGROUND: Highly potent dopamine D(2) receptor antagonistic antipsychotics may
      induce hyperprolactinemia. Conversely, drugs for the treatment of prolactinoma
      may activate dopamine D2 receptors, which can induce or aggravate psychosis.
      Aripiprazole, as a partial D(2) receptor agonist, may be the drug of choice in
      patients suffering from both psychosis and prolactinoma. OBJECTIVE: We evaluated
      the effects of aripiprazole on the size of a cystic macroadenoma by magnetic
      resonance imaging and on prolactin levels in a patient suffering from psychosis
      and prolactinoma. METHOD: This is a case report of a 53-year-old female patient
      with a chronic psychotic disorder and moderate mental retardation who had
      developed a prolactinoma that was resected but still had residual adenoma and
      hyperprolactinemia. Antipsychotic medication was switched from risperidone to
      aripiprazole before a dopamine agonist was initiated. RESULTS: After change in
      treatment, there were reductions in serum prolactin levels, tumor size and visual
      field defects. We observed no psychotic decompensation. CONCLUSION: The
      combination of aripiprazole and quinagolide could be considered as an effective
      treatment in patients suffering from both psychosis and a prolactinoma.

PMID- 21872336
TI  - Taming hornets: the therapeutic relationship in successful treatment of
      delusional infestation.

PMID- 21872337
TI  - Bupropion-induced psychosis: folklore or a fact? A systematic review of the
      literature.
AB  - OBJECTIVE: Bupropion is a substituted phenyl-ethylamine that is extensively
      utilized for the treatment of major depressive disorder and for smoking
      cessation. It is a reuptake inhibitor of dopamine and norepinephrine, and it also
      has some nicotinic antagonism. There are concerns that it may increase the risk
      of psychosis due to its dopaminergic effects. Our objective is to review the
      literature and analyze the risk of bupropion precipitating a psychotic illness in
      the general population as well as in the populations with a history of psychotic
      symptoms. METHODS: A Medline database search limited to human and English
      language studies was conducted using the keywords "bupropion" and "psychosis." A
      total of 23 articles were selected based on the relevance of the articles and
      their references. The data from these articles were collated. RESULTS: Collated
      data show that there is some evidence to suggest that bupropion may cause or
      worsen psychosis in selected subpopulations. Higher doses of bupropion appear
      more likely to be associated with the outcome severity. Preexisting psychotic
      symptoms, substance abuse and drug interactions also seem to increase the risk.
      Concurrent use of antipsychotics at adequate doses appears to be protective.
      CONCLUSIONS: The literature is incomplete and in some cases contradictory. In
      selected cases, bupropion appears to be associated with the induction of
      psychotic symptoms in addition to the precipitation or worsening of an existing
      psychotic syndrome. Further research including controlled studies is required to
      clarify the risk of bupropion precipitating a psychotic illness in vulnerable
      populations.

PMID- 21872338
TI  - Sad benefit in face working memory: an emotional bias of melancholic depression.
AB  - Emotion biases feature prominently in cognitive theories of depression and are a
      focus of psychological interventions. However, there is presently no stable
      neurocognitive marker of altered emotion-cognition interactions in depression.
      One reason may be the heterogeneity of major depressive disorder. Our aim in the
      present study was to find an emotional bias that differentiates patients with
      melancholic depression from controls, and patients with melancholic from those
      with non-melancholic depression. We used a working memory paradigm for emotional
      faces, where two faces with angry, happy, neutral, sad or fearful expression had
      to be retained over one second. Twenty patients with melancholic depression, 20
      age-, education- and gender-matched control participants and 20 patients with non
      melancholic depression participated in the study. We analysed performance on the
      working memory task using signal detection measures. We found an interaction
      between group and emotion on working memory performance that was driven by the
      higher performance for sad faces compared to other categories in the melancholic
      group. We computed a measure of "sad benefit", which distinguished melancholic
      and non-melancholic patients with good sensitivity and specificity. However,
      replication studies and formal discriminant analysis will be needed in order to
      assess whether emotion bias in working memory may become a useful diagnostic tool
      to distinguish these two syndromes.

PMID- 21872339
TI  - Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble
      interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive
      disorder: a meta-analysis and meta-regression.
AB  - BACKGROUND: Many studies have explored the association between soluble
      interleukin-2 receptor (sIL-2R), cytokines and major depressive disorder (MDD).
      However, the results of these studies were not consistent. The aim of our study
      is to compare the levels of sIL-2R and cytokines in the blood between MDD
      patients and controls by a meta-analysis and to identify moderators accounting
      for potential heterogeneity in the levels of sIL-2R and cytokines in MDD patients
      versus controls by meta-regression analyses. METHODS: A comprehensive literature
      search was performed to identify studies comparing the levels of sIL-2R and
      cytokines between MDD patients and controls. We pooled the effect sizes for
      standardized mean differences (SMD) of the levels of sIL-2R and cytokines. We
      also performed meta-regression and sensitivity analyses to investigate the roles
      of age, gender, sample type, ethnic origin and selected studies' quality in
      explaining potential heterogeneity and differences in results respectively.
      RESULTS: Twenty-nine studies were selected for this analysis. The levels of sIL
      2R, TNF-alpha and IL-6 in MDD patients were significantly higher than those of
      healthy controls (SMD=0.555, p<0.001, SMD=0.567, p=0.010; SMD=0.680, p<0.001).
      Mean age of all subjects was a significant moderator to explain the high
      heterogeneity of IL-6. Sensitivity analysis found that European but not non
      European subjects have higher levels difference of sIL-2R, TNF-alpha and IL-1beta
      between MDD patients and controls. LIMITATION: The severity of MDD was not
      considered. CONCLUSION: The blood levels of sIL-2R, TNF-alpha and IL-6 were
      significantly higher in MDD patients than controls. Age, samples source and
      ethnic origins may play a potential role in heterogeneity.

PMID- 21872340
TI  - Spatial orientation constancy is impaired in anorexia nervosa.
AB  - In anorexia nervosa (AN), body distortions have been associated with parietal
      cortex (PC) dysfunction. The PC is also the anatomical substrate of a supramodal
      reference framework involved in spatial orientation constancy. Given the impaired
      spatial orientation constancy found in hemineglect, we sought to determine
      whether similar disturbances could be observed in anorexic patients. We
      investigated the effect of passive lateral body inclination on the tactile
      subjective vertical (SV). Fifty participants (25 AN patients and 25 healthy
      controls) were asked to manually set a rod into the vertical position under three
      postural conditions. For tilted conditions, we observed a significant deviation
      of the tactile SV towards the body. This effect was abnormally accentuated in AN
      patients and might be caused by higher weighting with respect to the egocentric
      frame of reference. Our findings reinforce the role of the PC in AN and suggest
      that this dysfunction affects spatial orientation constancy as well as body
      boundaries.

PMID- 21872341
TI  - Perceived parental protection and cortisol responses among young females with
      borderline personality disorder and controls.
AB  - Borderline personality disorder (BPD) has been associated with deviations in
      cortisol in response to interpersonal stressors. Identifying mechanisms
      contributing to such deviations may help to address emotional dysregulation and
      the increased risk of self-destructive behavior. While dysfunctional
      relationships to caregivers have been widely reported among individuals with BPD,
      their contribution to cortisol hyperresponsiveness has yet to be investigated.
      Fifty-one females (aged 18-24years) participated to assess the impact of BPD and
      the quality of protective care in mother-daughter relationships on stress
      responsiveness. Seventeen females with BPD and twenty females without BPD
      participated with their mothers in a videotaped parent-young adult conflict
      discussion. Fourteen non-BPD females without their mothers were assessed for
      cortisol levels without stress exposure. Salivary cortisol samples were collected
      at lab entry and 20 and 40min after the onset of the discussion. Results revealed
      a higher overall cortisol response in the BPD group upon lab entry. BPD
      participants reported less experienced protection in the mother-daughter
      relationship which was associated with higher cortisol levels on lab entry and
      higher distress at study end. Results point to the perceived quality of parental
      protection as likely to modulate the activity of the stress response system among
      BPD patients.

PMID- 21872342
TI  - Protection of mice against Chlamydophila abortus infection with a bacteriophage
      mediated DNA vaccine expressing the major outer membrane protein.
AB  - A bacteriophage-delivered DNA vaccine against Chlamydophila abortus was
      constructed by cloning a eukaryotic cassette containing the ompA gene (which
      expresses the Major Outer Membrane Protein) into a bacteriophage lambda vector.
      Four groups, each of 20 BALB/c mice were inoculated separately with the phage
      vaccine, a conventional DNA vaccine based on the same ompA expression cassette, a
      live attenuated vaccine (strain 1B) or the empty phage vector. The phage and DNA
      vaccines and empty phage vector were administered intramuscularly on days 0, 14
      and 28; the attenuated vaccine was given once on day 0. Half the animals in each
      group were challenged on day 42 by intraperitoneal injection of live C. abortus
      and sacrificed on day 49. Phage-vaccinated mice developed moderate antibody
      levels against C. abortus and yielded higher levels of IFN-gamma and IL-2
      compared with the attenuated live vaccine group. Clearance of chlamydiae from
      spleens was significantly better in the attenuated vaccine group compared with
      the phage vaccine group, while both groups were significantly superior to the DNA
      vaccine and control groups (p<0.01). Although levels of protection in the mouse
      model were lower in phage-vaccinated animals, than in 1B vaccinated animals,
      phage vaccines offer several other advantages, such as easier handling and
      safety, potentially cheaper production and no chance of reversion to virulence.
      Although these are preliminary results in a model system, it is possible that
      with further optimisation immunization with phage vaccines may provide a novel
      way to improve protection against C. abortus infection and trials in large
      animals are currently being initiated.

PMID- 21872343
TI  - Expression of SOCS1-7 and CIS mRNA in porcine tissues.
AB  - The Suppressor Of Cytokine Signaling (SOCS) proteins are key physiological
      regulators of the immune system. Little is known about tissue expression of SOCS
      and data in pigs are extremely scarce. In order to further study SOCS in pigs,
      preliminary data must be collected. In the current report, we first identified
      the three most suitable reference genes in ten porcine tissues. The beta-2
      microglobulin (B2MI) reference gene was most often particularly suitable in our
      conditions. Then, using three reference genes we determined the mRNA expression
      of SOCS1-7 and CIS in every selected tissue. Constitutive mRNA expression was
      identified for all the members of the SOCS family in the ten tissues.
      Interestingly, the constitutive mRNA expression of SOCS1, SOCS3, SOCS7 and CIS
      was rather heterogeneous between tissues while for SOCS2, SOCS4, SOCS5 and SOCS6
      differences of expression were less obvious. Highest CIS and SOCS mRNA
      expressions were observed in large intestine (SOCS1, SOCS3, SOCS4, SOCS6, and
      CIS), small intestine (SOCS1, SOCS4, SOCS6, and CIS), spleen (SOCS2, SOCS3,
      SOCS5, SOCS7, and CIS), trachea (SOCS3) and thymus (SOCS1, SOCS2, SOCS4, SOCS7,
      and CIS). These data will help for further studies about the role of SOCS
      proteins in the control of porcine innate and adaptive responses.

PMID- 21872344
TI  - Development and characterization of mouse monoclonal antibodies reactive with
      chicken interleukin-2 receptor alphalpha chain (CD25).
AB  - This study was carried out to develop and characterize mouse monoclonal
      antibodies (mAbs) against chicken CD25 (chCD25), the alpha chain of the
      interleukin-2 (IL-2) receptor. A recombinant chimeric chCD25/IgG4 fusion protein
      was expressed in Chinese hamster ovary (CHO) cells and isolated from spent cell
      culture medium by protein G affinity chromatography. Purified chCD25 protein was
      used to immunize mice, from which 54 stable hybridomas secreting chCD25 mAbs were
      produced. Two mAbs, chCD25-32 and chCD25-54, with high binding affinity for
      chCD25-expressing CHO cells were selected for further characterization. By flow
      cytometry, both mAbs detected cells in the spleen, bursa of Fabricius, intestinal
      duodenum, and immunostained established chicken T cell, B cell, and macrophage
      cell lines. Both mAbs reacted with a 55 kDa protein on Western blots of lysates
      from concanavalin A (Con A)-stimulated spleen mononuclear cells. Intraperitoneal
      injection of chickens with bacterial lipopolysaccharide increased the percentage
      of chCD25(+) spleen cells by approximately 4-fold compared with untreated
      animals. In vitro stimulation of spleen cells with Con A increased the percentage
      of chCD25(+) cells by up to 50-fold compared with cells treated with medium
      alone. Finally, the chCD25-32 mAb suppressed IL-2-driven spleen cell
      proliferation and reduced IL-2-induced nitric oxide production. These mAbs may be
      useful for future investigation of chicken regulatory T cells.

PMID- 21872345
TI  - Dopamine up-regulates Th17 phenotype from individuals with generalized anxiety
      disorder.
AB  - Our objective was to evaluate the effect of stress-related dose of dopamine (DA)
      on the in vitro proliferation and cytokine production in polyclonally-activated T
      cells from healthy individuals or individuals with generalized anxiety disorder
      (GAD). Our results demonstrated that cell cultures from GAD group proliferated
      less following T cell activation, as compared with control group. The addition of
      DA reduced the proliferative response in cell cultures from healthy but not from
      GAD individuals. The cytokine profile in GAD individuals revealed Th1 and Th2
      deficiencies associated with a dominant Th17 phenotype, which was enhanced by DA.
      A similar DA-induced immunomodulation was also observed in PPD-activated cell
      cultures from GAD individuals. Unlike the control, DA-enhanced Th17 cytokine
      production in GAD individuals was not affected by glucocorticoid. In conclusion,
      our results show that the T cell functional dysregulation in GAD individuals is
      significantly amplified by DA. These immune abnormalities can have impact in
      increasing the susceptibility of individuals with anxiety disorders to infectious
      diseases and inflammatory/autoimmune disorders.

PMID- 21872347
TI  - Paediatric traffic accident and obstructive sleep apnoea by antrochoanal polyps:
      case report and literature review.
AB  - Antrochoanal polyps are hyperplasias of the nasal mucosa, which have their origin
      in the maxillary sinus and extend through the nasal cavity and the choanae into
      the naso- and oropharynx. In children antrochoanal polyps represent one of the
      more frequent manifestations of paediatric nasal polyposis. Most studies on
      antrochoanal polyps in children report only on nasal obstruction, hyponasal
      speech and snoring, which are also encountered in the most common cause of
      obstructive sleep apnoea syndrome; i.e. adenoid or tonsillar hyperplasia. Only
      very few studies report on additional health hazards by antrochoanal polyps
      ranging from obstructive sleep apnoea syndrome to swallowing disorders and
      cachexia. We present the case of an 8 year old girl with a bicycle accident
      caused by excessive daytime sleepiness and obstructive sleep apnoea syndrome due
      to an extensive antrochoanal polyp. After a transnasal polypectomy and meatotomy
      type II the obstructive sleep apnoea and day time sleepiness resolved completely.
      Awareness of this additional health hazard is important and correct evaluation
      and timely diagnosis of a potential antrochoanal polyp is mandatory because
      minimally invasive rhinosurgery is highly curative in preventing further
      impending problems.

PMID- 21872346
TI  - Lipid arrays identify myelin-derived lipids and lipid complexes as prominent
      targets for oligoclonal band antibodies in multiple sclerosis.
AB  - The presence of oligoclonal bands of IgG (OCB) in cerebrospinal fluid (CSF) is
      used to establish a diagnosis of multiple sclerosis (MS), but their specificity
      has remained an enigma since its first description over forty years ago. We now
      report that the use of lipid arrays identifies heteromeric complexes of myelin
      derived lipids as a prominent target for this intrathecal B cell response.

PMID- 21872348
TI  - Autologous fat transfer in velopharyngeal insufficiency: indications and results
      of a 25 procedures series.
AB  - OBJECTIVE: To assess the efficiency of autologous fat transfer (AFT/Coleman
      procedure) in the management of velopharyngeal insufficiency (VPI). SETTINGS:
      Tertiary academic center, retrospective case series over a 4 year period. Pre-
      and post-speech assessment by a speech pathologist using the Borel-Maisonny
      scale. PATIENTS AND METHOD: Twenty-five (25) procedures were performed on 22
      patients during the considered period. Mean age at surgery was 12.4 +/- 4.1 years
      old. Main associated conditions were 22q11 deletion (n=6 including 2 with cleft
      palate), isolated cleft palate (n=3), and Robin sequence (n=2). Indications were
      VPI grade 2a (n=5), 2b (n=11) and 3 (n=6), despite prolonged speech therapy (pre
      op mean duration: 4.2 years) and previous surgery (velopharyngoplasty, n=13).
      Four patients had a contraindication of velopharyngoplasty (aberrant internal
      carotid arteries). RESULTS AND CONCLUSION: Fat harvesting sites were umbilicus
      (n=23) and buttock (n=2). Mean injected fat volume was 7.8 ml, in the posterior
      wall of the pharynx (n=25) the soft palate (n=15), the peritonsillar arches
      (n=3), and the pre-existing flap (n=3). Mean follow-up was 17 months. Two
      patients relapsed once and one patient twice, requiring additional injections.
      Final post-operative examination 1 year after the last procedure showed an
      improvement of speech in 90% of cases (grade 1, n=2; 1/2a, n=5; 2a n=10; 2b,
      n=5). AFT is a safe technique indicated in the primary and secondary management
      of VPI, with stable results on speech. However, if a complete return to normal is
      difficult to achieve, its simplicity allows multiple procedures in the same
      patient.

PMID- 21872349
TI  - Are frail older people less exposed to abuse in nursing homes as compared to
      community-based settings? Statistical analysis of Slovenian data.
AB  - INTRODUCTION: Although international research in recent years has often focused
      on elder abuse, its extent is not clear in community-based settings and even
      bigger mystery in nursing homes. BACKGROUND: Until now in the literature it has
      in most cases only been assumed that nursing homes offer better protection from
      abuse for frail older people. METHODS: A cross-sectional research design was
      applied by use of structured interviews. Those involved were frail older people
      (n=300) who were in need of some sort of professional nursing assistance.
      RESULTS: Nursing home accommodation was extracted as the strongest predictor,
      significantly reducing the risk of physical abuse (odds ratio, OR 0.1, 95%
      confidence interval, 95% CI 0.0-0.3) and financial abuse (OR 0.2, 95% CI 0.1
      0.4). Spouses and sons were revealed as the most regular perpetrators of physical
      and financial abuse. The results showed no statistical significance between
      settings as predictors of the occurrence of mental abuse (OR 0.9, 95% CI 0.5
      1.6). DISCUSSION: Results of the statistical analysis add to the general
      assumption that nursing home accommodation offers protection for frail older
      people in escaping physical and financial abuse. CONCLUSION: In their clinical
      practice, community nurses should give special attention to frail older people
      who, besides their healthcare needs, are also heavily dependent in the activities
      of daily living (ADLs). In order to combat elder abuse, conditions in the family
      should be regularly verified.

PMID- 21872350
TI  - Percutaneous catheter-based cryoablation of the renal artery is effective for
      sympathetic denervation in a sheep model.

PMID- 21872351
TI  - General anxiety of adolescents and adults with congenital heart disease is
      comparable with that in healthy controls.
AB  - OBJECTIVE: This study aimed to compare situational and trait anxiety levels in
      patients with congenital heart disease (CHD) with that in healthy controls and to
      investigate their correlation to the perceived health status. PATIENTS AND
      METHODS: From November 2007 to December 2009 in total 879 patients (405 female,
      15-71 years) with various CHD and 40 healthy controls completed the State-Trait
      Anxiety Inventory (STAI) to assess state and trait anxiety, the depression
      scaling instrument CES-D, and the health-related quality of life questionnaire SF
      36. RESULTS: In patients with CHD no increased anxiety as a trait could be found
      (Mann-Whitney Utest, p = .186). Only situational anxiety in the setting of an
      outpatient department in a tertiary center was increased compared to healthy
      controls (Mann-Whitney U test, p = .004). Anxiety was closely related to
      depression and to all of the nine SF-36 dimensions (r = -.149 to r = -.745,
      p<.001). CONCLUSIONS: In general, patients with CHD show a rather normal anxiety
      pattern compared to healthy controls. These symptoms of anxiety were strongly
      correlated with the perceived health status. Only situational anxiety levels at
      the hospital are increased and still remain an important challenge for doctors
      and psychologists.

PMID- 21872352
TI  - Impact of successful staged revascularization of a chronic total occlusion in the
      non-infarct-related artery on long-term outcome in patients with acute ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: Recently, a chronic total occlusion (CTO) in the non-infarct-related
      artery (non-IRA) was reported as an independent predictor of clinical outcome in
      patients with acute ST-segment elevation myocardial infarction (STEMI). The aim
      of this study was to investigate the clinical significance of staged
      revascularization for a CTO in the non-IRA for patients with STEMI. METHODS: A
      total of 136 patients with acute STEMI undergoing primary percutaneous coronary
      intervention (PCI) received staged revascularization (ranging 7-10 days) for a
      CTO in the non-IRA. Cardiac mortality and major adverse cardiac events (MACE)
      including death, recurrent myocardial infarction, repeat revascularization, and
      re-hospitalization because of heart failure during 2-year follow-up were
      recorded. RESULTS: Recanalization of totally occluded lesions in the non-IRA was
      successful in 87 (64%) patients for 93 lesions but failed in 49 (36%) patients.
      During 2-year follow-up, cardiac mortality was lower (8.0% vs. 20.4%, p = 0.036)
      and MACE-free survival was higher (78.2% vs. 61.2%, p = 0.042) in patients with
      successful than in those with failed revascularization of a CTO in the non-IRA.
      Multivariable analysis showed that after adjustment for possible confounders,
      successful recanalization of a CTO in the non-IRA was an independent predictor
      for 2-year cardiac mortality (HR = 0.145, 95% CI 0.047-0.446, P = 0.001) and MACE
      free survival (HR = 0.430, 95%CI 0.220-0.838, P = 0.013). CONCLUSION: Successful
      revascularization of a CTO in the non-IRA is associated with improved clinical
      outcomes in patients with STEMI undergoing primary PCI.

PMID- 21872353
TI  - Additional data supporting the use of statins to prevent contrast induced
      nephropathy.

PMID- 21872354
TI  - Relationship between oxidative stress and apoptotic markers in lymphocytes of
      diabetic patients with chronic non healing wound.
AB  - AIMS: Hyperglycemia causes generation of free radicals which leads to oxidative
      stress and apoptosis in various cells. The present study was undertaken to
      investigate the correlation between oxidative stress and apoptotic markers in
      lymphocytes of diabetic patients with chronic non healing wounds. METHODS: Thirty
      healthy, thirty uncontrolled type 2 diabetes mellitus (T2DM) and thirty
      uncontrolled T2DM with chronic, non healing, neuropathic diabetic foot patients
      were included in this study. Indices of oxidative stress inside the lymphocyte
      lysate were estimated by measuring content of superoxide dismutase (SOD),
      Catalase, Glutathione and malonaldialdehyde (MDA). Protein expression studies of
      pro and anti apoptotic markers were carried out to elucidate their possible
      involvement in diabetic context. RESULTS: SOD and MDA activity was significantly
      higher in the lymphocytes of diabetic patients having chronic, non healing
      diabetic wound as compared with healthy (p<0.001); whereas catalase and GSH
      activity was significantly reduced (p<0.001) in the same group. Expressions of
      pro apoptotic markers (Caspase-3, Fas and Bax) were significantly higher whereas
      reduced expression of anti-apoptotic marker (Bcl-2) were obtained in lymphocytes
      of diabetic and non diabetic individuals. CONCLUSIONS: Hyperglycemia confers pro
      apoptotic manifestations which are mostly through altered indices of oxidative
      stress within lymphocytic milieu.

PMID- 21872355
TI  - A web application for follow-up of results from a mobile device test battery for
      Parkinson's disease patients.
AB  - This paper describes a web-based system for enabling remote monitoring of
      patients with Parkinson's disease (PD) and supporting clinicians in treating
      their patients. The system consists of a patient node for subjective and
      objective data collection based on a handheld computer, a service node for data
      storage and processing, and a web application for data presentation. Using
      statistical and machine learning methods, time series of raw data are summarized
      into scores for conceptual symptom dimensions and an "overall test score"
      providing a comprehensive profile of patient's health during a test period of
      about one week. The handheld unit was used quarterly or biannually by 65 patients
      with advanced PD for up to four years at nine clinics in Sweden. The IBM Computer
      System Usability Questionnaire was administered to assess nurses' satisfaction
      with the web application. Results showed that a majority of the nurses were quite
      satisfied with the usability although a sizeable minority were not. Our findings
      support that this system can become an efficient tool to easily access relevant
      symptom information from the home environment of PD patients.

PMID- 21872356
TI  - Abnormality of the hepatocyte growth factor/MET pathway in pulmonary
      adenocarcinogenesis.
AB  - BACKGROUND: Signaling mediated by hepatocyte growth factor (HGF)/MET promotes
      multiple biological activities, including cell proliferation, motility, invasion,
      angiogenesis, and morphogenesis. Overexpression of HGF and MET and an increase of
      the MET gene copy number have recently been found in various cancers that had a
      poor outcome. Here we investigated the copy number of the MET gene and expression
      of MET and HGF in small pulmonary adenocarcinomas. METHODS: Tumor tissues were
      obtained from 106 pulmonary small adenocarcinomas 2 cm or less in diameter. MET
      gene copy number, and the expression of MET and HGF, were analyzed using
      fluorescence in situ hybridization (FISH) and immunohistochemistry, respectively.
      RESULTS: MET FISH-positive signals were observed in 11 (10.4%) of 106 cases. One
      case (0.9%) showed gene amplification and 10 (9.4%) exhibited high polysomy. High
      immunoreactivity for MET and HGF in tumor cells was found in 30 (28.3%) and 19
      cases (17.9%), respectively. HGF was also expressed in stromal cells in 32 cases
      (30.2%). No cases of non-invasive adenocarcinoma (adenocarcinoma in situ,
      localized bronchioloalveolar carcinoma) showed MET FISH-positive signals or high
      expression of HGF in the tumor cells. Expression of both MET and stromal HGF was
      stronger in invasive than in non-invasive adenocarcinoma. MET FISH-positive
      signals and high immunoreactivity for MET and HGF in tumor cells were associated
      with factors indicative of poor prognosis such as pleural invasion, vascular
      invasion, lymphatic permeation, lymph node metastasis, and nuclear grading.
      Univariate and multivariate analyses that included these factors showed that all
      statuses except for MET and HGF immunoreactivity were significantly associated
      with an increased risk of death. However, multivariate analysis revealed no
      independent factors related to poor prognosis. CONCLUSION: Our results suggest
      that abnormality of the HGF/MET pathway occurs during the course of progression
      from non-invasive to invasive pulmonary adenocarcinoma. An increased MET gene
      copy number is indicative of a poor outcome in patients with small pulmonary
      adenocarcinomas.

PMID- 21872357
TI  - Antiphospholipid antibodies and atherosclerosis: insights from rheumatoid
      arthritis--a five-year follow-up study.
AB  - OBJECTIVES: Life expectancy in rheumatoid arthritis (RA) patients is reduced by 3
      10 years, probably due to cerebrovascular and cardiovascular diseases associated
      with atherosclerosis. In the present study, we wanted to verify if previously
      reported IgA anti-beta 2-glycoprotein I (2GPI) antibodies possibly represented an
      independent risk factor for atherosclerosis in RA patients during a longer period
      of follow up. METHODS: The follow-up study (after 5.5 years) comprised all
      initially included patients and controls (premenopausal women, non-diabetic,
      normotensive at the start of the study), except for two RA patients (one died and
      one not available). The same clinical, laboratory and ultrasound assessments were
      performed. RESULTS: Patients and controls were divided into three categories:
      Intima-media thickness (IMT) progressors, plaque progressors, IMT and plaque
      progressors. In controls, 55% represented IMT progressors and 5% IMT and plaque
      progressors. No statistically significant differences were detected comparing the
      progressors with delta (Delta=difference between follow-up and baseline study for
      each group in a time span of 5.5 years) LDL cholesterol, homocysteine and IgA
      anti-beta2GPI. In patients, there were 48.5% IMT progressors, 5.8% plaque
      progressors and 19.1% IMT and plaque progressors. The progression was
      statistically significant associated with the levels of Delta homocysteine and
      Delta apolipoprotein B but not with LDL cholesterol and IgA anti-beta2GPI.
      CONCLUSIONS: The follow-up study showed advanced atherosclerosis in RA patients
      compared to sex and age matched controls. However, we were not able to confirm
      our initial impression that IgA anti-beta2GPI might represent an independent risk
      factor for atherosclerosis.

PMID- 21872358
TI  - Pil1, an eisosome organizer, plays an important role in the recruitment of
      synaptojanins and amphiphysins to facilitate receptor-mediated endocytosis in
      yeast.
AB  - The eisosome protein Pil1 is known to be implicated in the endocytosis of Ste3,
      but the precise biological function of it during endocytosis is poorly
      understood. Here, we present data to reveal Pil1's role in receptor-mediated
      endocytosis. Using live cell imaging, we show that endocytic patches carrying
      Abp1 and Las17 persisted much longer in PIL1-deficient cells. The loss of Pil1
      also greatly affected both the scission efficiency and the frequency of formation
      of endocytic sites carrying Rvs161- and Rvs167-GFP. Furthermore, the mistargeting
      of the synaptojanins, Sjl1 and Sjl2, to the cytoplasm in pil1Delta cells suggests
      that Pil1 is required for the proper recruitment of the synaptojanins to
      endocytic sites. A severe motility defect of Abp1-GFP during its internalization
      in a codeletant of PIL1 and SJL2 indicates a functional interplay between them in
      endocytosis. Together, these results establish that Pil1 is involved in the
      recruitment of endocytic proteins to optimize endocytosis.

PMID- 21872359
TI  - Beliefs and emotional reactions in patients with benign paroxysmal positional
      vertigo: a longitudinal study.
AB  - OBJECTIVE: Psychologic studies in patients with benign paroxysmal positional
      vertigo (BPPV) are scarce, considering the high frequency of the disorder. We
      performed a repeated-measures design questionnaire study in a cohort of patients
      with BPPV before and after treatment to investigate the dynamics of the
      psychologic findings and possible treatment consequences. METHODS: Thirty-seven
      consecutive patients with idiopathic BPPV participated in the study. During the
      first visit and 2 to 3 months after therapy, the patients completed 4
      questionnaires: the Dizziness Handicap Inventory, the Illness Perception
      Questionnaire-Revised, the Intolerance of Uncertainty Scale, and the State-Trait
      Anxiety Inventory. RESULTS: The scores for all questioned items did not change
      before and after treatment except for the physical handicap scores. Correlation
      was found between the grade of functional and emotional impact of the disease and
      belief in consequences as well as anxiety levels of the patients. Moreover,
      uncertainty scores were in correlation with emotional impact, anxiety levels, and
      perceived consequences of the disease. The belief in personal control of the
      condition was correlated with the belief in treatment control and understanding
      of the disease. CONCLUSION: The main finding in this study is the lack of a
      significant change in beliefs and emotional reactions in patients with BPPV after
      treatment of their condition. Physicians dealing with BPPV should be aware that
      the disease is not solely a somatic condition but has a serious impact on the
      patient's mental state. Selected patients might benefit from anxiolytic
      medication.

PMID- 21872360
TI  - Culture-change training: nursing facility staff perceptions of culture change.
AB  - Identifying effective alternative strategies for training staff and implementing
      culture change can be useful to nursing facilities striving to provide optimal
      resident-centered care. This study assessed the perceptions of nearly 400 nursing
      facility staff experiencing organizational culture change. Formal and informal
      training methods were used. We used a pre- and post-test to evaluate leadership
      practices and 6 subscales related to culture change (systemwide culture change,
      resident choice, organization design, empowering supervision, job design,
      decision making, and permanent assignments). Staff of formally trained facilities
      perceived improvements in all subscales; 2 were statistically significant
      (resident choice and organization design). Respondents for informally trained
      facilities identified improvement in decision making, although this was not
      statistically significant. Formalized culture-change training produced better
      outcomes than did the informal strategy. Culture change is a complex process and
      may continue to evolve over time. A 3-year evaluation period may be insufficient
      to demonstrate the full extent of these changes.

PMID- 21872361
TI  - Astrocytes in aged nonhuman primate brain gray matter synthesize excess
      hyaluronan.
AB  - The glycosaminoglycan hyaluronan (HA) accumulates in central nervous system
      lesions where it limits astrogliosis but also inhibits oligodendrocyte progenitor
      cell (OPC) maturation. The role of hyaluronan in normative brain aging has not
      been previously investigated. Here, we tested the hypothesis that HA accumulates
      in the aging nonhuman primate brain. We found that HA levels significantly
      increase with age in the gray matter of rhesus macaques. HA accumulation was
      linked to age-related increases in the transcription of HA synthase-1 (HAS1)
      expressed by reactive astrocytes but not changes in the expression of other HAS
      genes or hyaluronidases. HA accumulation was accompanied by increased expression
      of CD44, a transmembrane HA receptor. Areas of gray matter with elevated HA in
      older animals demonstrated increased numbers of olig2(+) OPCs, consistent with
      the notion that HA may influence OPC expansion or maturation. Collectively, these
      data indicate that HAS1 and CD44 are transcriptionally upregulated in astrocytes
      during normative aging and are linked to HA accumulation in gray matter.

PMID- 21872363
TI  - White matter fractional anisotropy predicts balance performance in older adults.
AB  - Aging is characterized by brain structural changes that may compromise motor
      functions. In the context of postural control, white matter integrity is crucial
      for the efficient transfer of visual, proprioceptive and vestibular feedback in
      the brain. To determine the role of age-related white matter decline as a
      function of the sensory feedback necessary to correct posture, we acquired
      diffusion weighted images in young and old subjects. A force platform was used to
      measure changes in body posture under conditions of compromised proprioceptive
      and/or visual feedback. In the young group, no significant brain structure
      balance relations were found. In the elderly however, the integrity of a cluster
      in the frontal forceps explained 21% of the variance in postural control when
      proprioceptive information was compromised. Additionally, when only the
      vestibular system supplied reliable information, the occipital forceps was the
      best predictor of balance performance (42%). Age-related white matter decline may
      thus be predictive of balance performance in the elderly when sensory systems
      start to degrade.

PMID- 21872362
TI  - Distinctive disruption patterns of white matter tracts in Alzheimer's disease
      with full diffusion tensor characterization.
AB  - To characterize the white matter structural changes at the tract level and tract
      group level, comprehensive analysis with 4 metrics derived from diffusion tensor
      imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups,
      namely limbic, commissural, association, and projection tracts, include white
      matter tracts of similar functions. Diffusion tensor imaging data were acquired
      from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild
      cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based
      approach was used to survey 30 major cerebral white matter tracts with the
      measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive
      functions of AD patients were also measured to correlate with the structural
      changes of white matter. Synchronized structural changes of cingulum bundle and
      fornix, both of which are part of limbic tract group, were revealed. Widespread
      yet distinctive structural changes were found in limbic, commissural,
      association, and projection tract groups between control and AD subjects.
      Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural
      tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection
      tracts are significantly different between AD patients and control subjects. In
      contrast, the comparison between aMCI and control subjects shows disruption only
      in the limbic and commissural tract groups of aMCI subjects. MD values of all
      tract groups of AD patients are significantly correlated to cognitive functions.
      Difference between AD and control and that between aMCI and control indicates a
      progression pattern of white matter disruption from limbic and commissural tract
      group to other tract groups. High correlation between FA, MD, and RD measurements
      from limbic tracts and cortical atrophy suggests the disruption of the limbic
      tract group is caused by the neuronal damage.

PMID- 21872365
TI  - Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl,
      and 3-carboxyhydrazido coumarin derivatives.
AB  - Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58)
      coumarins have been synthesized in high yields (72-99%) and tested in vitro for
      their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity.
      Different substituents on the coumarin nucleus were evaluated for their effect on
      biological activity and isoform selectivity. Substitution at position C7 of the 3
      ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3,
      were important to obtain highly potent and selective hMAO-B inhibitors with
      IC(50) values in the nanomolar range. Some derivatives were also submitted to a
      stability test and showed no chemical cleavage in vitro.

PMID- 21872364
TI  - Aging impairs hippocampus-dependent long-term memory for object location in mice.
AB  - The decline in cognitive function that accompanies normal aging has a negative
      impact on the quality of life of the elderly and their families. Studies in
      humans and rodents show that spatial navigation and other hippocampus-dependent
      functions are particularly vulnerable to the deleterious effects of aging.
      However, reduced motor activity and alterations in the stress response that
      accompany normal aging can hinder the ability to study certain cognitive
      behaviors in aged animals. In an attempt to circumvent these potential confounds,
      we used a hippocampus-dependent object-place recognition task to show that long
      term spatial memory is impaired in aged mice. Aged animals performed similarly to
      young adult mice on an object recognition task that does not rely on hippocampal
      function.

PMID- 21872366
TI  - Synthesis, hypnotic properties and molecular modeling studies of 1,2,7,9-tetraaza
      spiro[4.5]dec-2-ene-6,8,10-triones.
AB  - 1,3-Dipolar cycloaddition reaction of nitrilimines with 5-arylidene-1,3-dimethyl
      2,4,6-pyrimidinetriones 1a-i afforded 7,9-dimethyl-1,3,4-triaryl-1,2,7,9-tetraaza
      spiro[4.5]dec-2-ene-6,8,10-triones 3a-k in a high regioselective manner. Single
      crystal X-ray study of 3d added a conclusive support for the assigned structure.
      Potentiating effects of the synthesized compounds 3a-k (at a dose of 25 mg/kg
      body weight) on hypnotic action of sodium thiopental (at a dose of 75 mg/kg body
      weight i.p.) were investigated in vivo using Albino mice according to the
      standard method. Most of the tested compounds revealed promising hypnotic
      potentiating effects especially compounds 3k and 3e that could be nominated as
      short-acting hypnotics. A hypothesis of molecular modeling study, including
      fitting of the synthesized compounds into 3D-pharmacophore using Discovery Studio
      2.5 software and their docking into optimized homology model of GABA(A)-alpha(1)
      showed good results consistent with the observed pharmacological properties.

PMID- 21872367
TI  - Discovery of a new class of HMG-CoA reductase inhibitor from Polyalthia
      longifolia as potential lipid lowering agent.
AB  - Bioassay guided fractionation of the ethanolic extract of Polyalthia longifolia
      var. pendula, led to the discovery of the clerodane diterpene, 16alpha
      hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide (1), as a new structural class of
      HMG-CoA reductase inhibitor. Importantly, the in vivo effects of 1 corroborated
      well with its molecular docking analysis and also with its hamster plasma
      pharmacokinetics.

PMID- 21872368
TI  - [Eyes of different colours].

PMID- 21872369
TI  - [Chronic headache in a 37-year-old woman].

PMID- 21872370
TI  - [Rituximab to treat ANCA-associated vasculitis].

PMID- 21872371
TI  - Distribution of bioelectrical impedance vector values in multi-ethnic infants and
      pre-school children.
AB  - BACKGROUND & AIMS: Ethnicity may influence bioimpedance values. The goal of this
      study was to measure total body impedance vector in infants and pre-school
      children in Brazil and compare them with those reported in other countries.
      METHODS: We analyzed bioelectrical impedance from a sample of 255 healthy
      Brazilian children, aged 1-36 months, using the RXc graph method (tetrapolar
      analysis at 50 kHz frequency). The 95%, 75% and 50% tolerance ellipses were
      plotted by age group. RESULTS: The mean impedance vector showed migration across
      age groups, with progressive higher reactances and lower resistances as age
      increased. The mean bioimpedance vectors from the present sample of Brazilian
      children were different from those of European children of the same age ranges.
      CONCLUSIONS: Our results confirm the importance of defining reference values of
      total body impedance vector for each country in view of the considerable ethnic
      diversity among different geographical areas.

PMID- 21872372
TI  - Micronutrients in pregnancy: current knowledge and unresolved questions.
AB  - Micronutrient status is increasingly recognized to play an important role in the
      health and well-being of pregnant women and in the development and long-term
      health of the offspring. On 26th - 28th February 2009, The Child Health
      Foundation invited leading experts in this area to a scientific workshop at
      Obergurgl, Austria to review and critically discuss current knowledge, to
      identify issues that may need to be addressed in future recommendations, and to
      highlight priorities and opportunities for future research. This report
      summarizes updated key conclusions of the workshop with regards to
      micronutrients' intake and physiological role related to mother, placenta and
      fetus, as well as relevance for adverse pregnancy and long-term outcomes.

PMID- 21872373
TI  - Development of a new aerosol monitoring system and its application in Fukushima
      nuclear accident related aerosol radioactivity measurement at the CTBT
      radionuclide station in Sidney of Canada.
AB  - A high volume aerosol sampler ("Grey Owl") has been designed and developed at the
      Radiation Protection Bureau, Health Canada. Its design guidance is based on the
      need for a low operational cost and reliable sampler to provide daily aerosol
      monitoring samples that can be used as reference samples for radiological
      studies. It has been developed to provide a constant air flow rate at low
      pressure drops (~3 kPa for a day sampling) with variations of less than +/-1% of
      the full scale flow rate. Its energy consumption is only about 1.5 kW for a
      filter sampling over 22,000 standard cubic meter of air. It has been demonstrated
      in this Fukushima nuclear accident related aerosol radioactivity monitoring study
      at Sidney station, B.C. that the sampler is robust and reliable. The results
      provided by the new monitoring system have been used to support decision-making
      in Canada during an emergency response.

PMID- 21872374
TI  - Bleeding and thrombotic complications of kidney disease.
AB  - With the rising prevalence of kidney disease, clinicians are increasingly faced
      with concerns about potential thrombotic and bleeding complications. Thrombotic
      risk, both arterial and venous, predominates with all severities of kidney
      disease but bleeding manifestations become an additional concern particularly
      with uraemia. This article reviews these contrasting problems and discusses
      strategies for prevention and management in the context of renal impairment,
      renal replacement therapy and renal transplantation.

PMID- 21872375
TI  - Polybrominated diphenyl ethers (PBDEs) in soils along a rural-urban-rural
      transect: sources, concentration gradients, and profiles.
AB  - This study reports concentrations of PBDEs in surface soil samples collected
      along a 140 km transect across Kuwait to assess the role of urban centers as
      sources of persistent organic pollutants to the surrounding environment. The
      SigmaPBDE concentrations varied by a factor of ~250 and ranged from 289 to 80,078
      pgg (-1)d.w. The concentrations of PBDEs in Kuwait City were significantly higher
      (p<0.01) than those collected from sites outside the city supporting the
      hypothesis that urban centers are sources of PBDEs. The congener profiles were
      dominated by BDE-209, accounting for 93% of the PBDEs in the soil samples. The
      concentrations of all congeners (except BDE-209) were highly correlated with
      percent organic carbon (%OC) (p>0.05) when the data from Kuwait City was omitted
      from the analysis. These findings suggest that soil concentrations outside the
      urban centers were close to equilibrium with the atmosphere.

PMID- 21872377
TI  - The pathogenesis of IgA nephropathy: what is new and how does it change
      therapeutic approaches?
AB  - Immunoglobulin A (IgA) nephropathy is the most common glomerulonephritis
      worldwide. For example, in Japan, full-blown IgA nephropathy has been detected in
      ~1.5% of all allograft kidneys at the time of transplant. Genetic and
      environmental modifiers, as well as generic progression factors (eg,
      hypertension), must have a major role in determining who will become clinically
      overt and who will experience progression. In patients with clinically overt IgA
      nephropathy and/or progressive disease, it now is relatively well established
      that the pathogenesis involves 6 major steps: (1) Increased occurrence of IgA1
      with poor galactosylation in the circulation. This might relate to the migration
      of mucosal B cells to bone marrow, where they produce "correct" poorly
      galactosylated IgA. Modulation of mucosal immunity may offer new therapeutic
      options. (2) Generation of IgG antibodies against poorly galactosylated IgA1.
      This could lay the foundation for immunosuppression, whereas detection of such
      IgG autoantibodies may accommodate the noninvasive monitoring of IgA nephropathy.
      (3) Mesangial deposition and/or formation of IgG-IgA1 or IgA1-IgA1 complexes. (4)
      Activation of mesangial IgA receptors and/or complement; both lend themselves to
      therapeutic interference. (5) Mesangial cell damage and activation of secondary
      pathways, such as overproduction of platelet-derived growth factor, which can be
      targeted specifically. (6) Activation of pathomechanisms that are not specific
      for IgA nephropathy and that drive glomerulosclerosis and tubulointerstitial
      fibrosis. Although at present our therapeutic armamentarium is still limited
      largely to supportive care and immunosuppression in some instances, these new
      insights can be expected to yield novel, perhaps individualized, therapeutic
      options in primary and recurrent IgA nephropathy.

PMID- 21872378
TI  - Multi-intervention management of calciphylaxis: a report of 7 cases.
AB  - Calcific uremic arteriolopathy (calciphylaxis) is a devastating but rare
      complication seen predominantly in dialysis patients that often is fatal. Because
      of the rarity of the disease and the multifactorial nature of its cause, no
      clinical trials have been conducted to date to determine the best therapy for the
      condition. We report a case series of 7 patients at a single institution in whom
      a systematic multi-interventional treatment strategy was implemented, consisting
      of trigger-agent cessation (calcium-based phosphate binders, alphacalcidol, and
      warfarin), wound management, and antibiotic therapy, supplemented by intensified
      hemodialysis (4 hours daily for 7 days followed by 5-6 times weekly), intravenous
      sodium thiosulfate (12.5-25 g intravenously 3 times a week), and attempted oxygen
      therapy (given through a face mask or hyperbaric chamber as tolerated by patient
      circumstance). Treatments selected were based on literature review, consensus
      discussion, and attempts to address the physiologic disturbances that underlie
      the condition. All 7 patients identified with biopsy-proven calcific uremic
      arteriolopathy were treated with this regimen in 2007-2010, with 6 of 7 showing
      complete recovery. We suggest that consistent implementation of a multi
      interventional approach may alter the course of this devastating disease. Further
      studies are needed to confirm and extend these findings.

PMID- 21872379
TI  - Segmental arterial mediolysis: report of 2 cases and review of the literature.
AB  - Segmental arterial mediolysis (SAM) is an idiopathic noninflammatory vasculopathy
      involving small to medium arteries, usually in the abdomen, although arteries in
      the cerebral and coronary circulations also may be affected. Some cases present
      as abdominal apoplexy due to aneurysmal rupture, but ischemia and infarction also
      occur. Not uncommonly, SAM may be misdiagnosed as a systemic necrotizing
      vasculitis. We present 2 patients with bilateral renal infarctions, cerebral
      arterial dissections, and visceral artery microaneurysms. Both were diagnosed
      initially as polyarteritis nodosa. The diagnosis was changed to SAM, in one case
      based on clinical and radiologic features, and in the other, on an open wedge
      kidney biopsy. We discuss the differential diagnosis and review the literature on
      SAM.

PMID- 21872376
TI  - Sulodexide for kidney protection in type 2 diabetes patients with
      microalbuminuria: a randomized controlled trial.
AB  - BACKGROUND: Sulodexide, a heterogenous group of sulfated glycosaminoglycans,
      includes low-molecular-weight heparin (~80% +/- 8%), high-molecular-weight
      heparin (~5% +/- 3%), and dermatan (~20% +/- 8%), with a mean molecular weight of
      ~9 kDa. The drug is absorbed orally and has no anticoagulant effect in the doses
      used. Small preliminary studies consistently showed sulodexide to be associated
      with decreased albuminuria in patients with diabetes. STUDY DESIGN: We conducted
      a multicenter placebo-controlled double-blinded study to determine the effect of
      sulodexide on urine albumin excretion in patients with type 2 diabetic
      nephropathy. SETTING & PARTICIPANTS: Patients with type 2 diabetes and urine
      albumin-creatinine ratios (ACRs) of 35-200 mg/g in men and 45-200 mg/g in women
      were enrolled. Serum creatinine level was <1.5 mg/dL. Blood pressure goal was
      130/80 mm Hg. A maximum US Food and Drug Administration-approved dose of an
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for a
      minimum of 4 months before randomization was required. INTERVENTION: The study
      drug was sulodexide, 200 mg/d. OUTCOME & MEASUREMENTS: The primary end point was
      normoalbuminuria (ACR <20 mg/g and a decrease >25%) or 50% decrease in baseline
      ACR. RESULTS: In 1,056 randomly assigned patients with a mean baseline ACR of
      107.8 +/- 83.7 mg/g, comparing the sulodexide versus placebo groups, the primary
      end point was achieved in 16.5% versus 18.4%; normoalbuminuria, in 7.9% versus
      6.1%; and a 50% decrease in albuminuria, in 15.4% versus 17.6%. The relative
      probability of any given change in albuminuria was identical in both groups.
      LIMITATIONS: We were unable to determine whether the administered sulodexide was
      absorbed from the gastrointestinal tract. CONCLUSION: Sulodexide failed to
      decrease urine albumin excretion in patients with type 2 diabetic nephropathy and
      microalbuminuria.

PMID- 21872380
TI  - Perceptual training strongly improves visual motion perception in schizophrenia.
AB  - Schizophrenia patients exhibit perceptual and cognitive deficits, including in
      visual motion processing. Given that cognitive systems depend upon perceptual
      inputs, improving patients' perceptual abilities may be an effective means of
      cognitive intervention. In healthy people, motion perception can be enhanced
      through perceptual learning, but it is unknown whether this perceptual plasticity
      remains in schizophrenia patients. The present study examined the degree to which
      patients' performance on visual motion discrimination can be improved, using a
      perceptual learning procedure. While both schizophrenia patients and healthy
      controls showed decreased direction discrimination thresholds (improved
      performance) with training, the magnitude of the improvement was greater in
      patients (47% improvement) than in controls (21% improvement). Both groups also
      improved moderately but non-significantly on an untrained task-speed
      discrimination. The large perceptual training effect in patients on the trained
      task suggests that perceptual plasticity is robust in schizophrenia and can be
      applied to develop bottom-up behavioral interventions.

PMID- 21872381
TI  - Diagnostic challenge of annular abscess in a patient with prosthetic aortic
      valve: can F-fluorodeoxyglucose positron emission tomography be helpful?

PMID- 21872382
TI  - Bronchiolitis obliterans in children: a ghostly journey to the origin.

PMID- 21872383
TI  - Minimizing external indirect health costs due to aerosol population exposure: a
      case study from Northern Italy.
AB  - Environmental Agencies require Decision Support Systems, in order to plan Air
      Quality Policies considering the cost of emission reduction measures and the
      human health effects (with related social costs). The use of Decision Support
      Systems is also useful to spread information to general public, explaining the
      effectiveness of proposed air quality plans. In this paper, a multi-objective
      approach to control PM10 concentration at a regional level is presented. The
      problem considers both the internal costs (due to the implementation of emission
      reduction measures) and the external costs (due to population exposure to high
      PM10 concentrations). To model PM10 concentrations, a single surrogate model is
      used for the entire domain, allowing the implementation of a very efficient
      optimization procedure. The surrogate model is derived through a set of 10
      simulations, performed using a Chemistry Transport Model fed with different
      emission reduction scenarios. The methodology is applied to Northern Italy, a
      region affected by very high PM10 concentrations that exceed the limit values
      specified by the EU legislation.

PMID- 21872384
TI  - A two-stage support-vector-regression optimization model for municipal solid
      waste management - a case study of Beijing, China.
AB  - In this study, a two-stage support-vector-regression optimization model (TSOM) is
      developed for the planning of municipal solid waste (MSW) management in the urban
      districts of Beijing, China. It represents a new effort to enhance the analysis
      accuracy in optimizing the MSW management system through coupling the support
      vector-regression (SVR) model with an interval-parameter mixed integer linear
      programming (IMILP). The developed TSOM can not only predict the city's future
      waste generation amount, but also reflect dynamic, interactive, and uncertain
      characteristics of the MSW management system. Four kernel functions such as
      linear kernel, polynomial kernel, radial basis function, and multi-layer
      perception kernel are chosen based on three quantitative simulation performance
      criteria [i.e. prediction accuracy (PA), fitting accuracy (FA) and over all
      accuracy (OA)]. The SVR with polynomial kernel has accurate prediction
      performance for MSW generation rate, with all of the three quantitative
      simulation performance criteria being over 96%. Two cases are considered based on
      different waste management policies. The results are valuable for supporting the
      adjustment of the existing waste-allocation patterns to raise the city's waste
      diversion rate, as well as the capacity planning of waste management system to
      satisfy the city's increasing waste treatment/disposal demands.

PMID- 21872385
TI  - Removal of faecal bacteria from septage by treating it in a full-scale duckweed
      covered pond system.
AB  - Performance of a full-scale duckweed-covered treatment system in removing faecal
      bacteria is presented. The system consisted of three ponds in series and received
      septage from holding tanks. Inflow averaged between 36 m(3) d(-1) in the cold
      season and 60 m(3) d(-1) in the warm season, resulting in a total hydraulic
      retention time of 88 and 58 days, respectively. Duckweed (Lemna minor) colonized
      the ponds in the summer and continued to grow in the cold season. Due to the
      difficult harvesting process of the duckweed biomass, the investigation of the
      treatment efficiency was carried out without plant harvesting. The system was
      monitored for temperature, pH, oxygen, chlorophyll-a, Escherichia coli and
      Enterococci. Duckweed growth resulted in chlorophyll-a concentration reduction
      from 924 to 13 MUg L(-1), causing neutral and anoxic conditions in the pond
      water. A temperature effect was noticed on the E. coli decay coefficient with a
      decreasing trend along the treatment system. Enterococci always decayed less than
      E. coli. Differences on decay coefficients and removal efficiencies were not
      observed between the three ponds for both bacterial types. Effluent quality in
      terms of E. coli was 489 and 1377 cfu/100 mL, in the warm and the cold seasons,
      respectively, with average removals of 99.65 +/- 1.46% and 99.33 +/- 3.03%. Total
      Enterococci removal was 88.91 +/- 23.1% in the warm season and 94.43 +/- 24.45%
      in the cold season, resulting in mean effluent values of 1058 and 1404 cfu/100
      mL, respectively. The seasonal differences in total removal efficiencies were
      insignificant for both bacterial types.

PMID- 21872387
TI  - The central nervous system solitary fibrous tumor: a review of clinical, imaging
      and pathologic findings among all reported cases from 1996 to 2010.
AB  - OBJECTIVE: Central nervous system (CNS) solitary fibrous tumor (SFT) is a rare
      lesion first identified as a unique entity in 1996. We describe two cases treated
      at the University of Florida followed by a review of all reported cases of CNS
      SFT between 1996 and 2010. METHODS: A review of the literature was performed to
      identify all reported cases of CNS SFT. RESULTS: 189 cases (including the two
      presented herein) were discovered, of which 46 were spinal and 143 were
      intracranial. Demographic, imaging, and pathologic findings are presented.
      Roughly 6% of reported lesions are malignant. Subtotal resection (STR) was
      associated with a 16-fold increased odds of recurrence (OR 15.9, 95% CI 5.5
      46.1), although mean follow-up was shorter in those cases of GTR without
      recurrence. CONCLUSION: CNS SFT is a rare lesion. Six percent of lesions are
      malignant. GTR is superior to STR although the degree of superiority is not
      clear.

PMID- 21872388
TI  - Antitumor activities of recombinant human interferon (IFN)-lambda1 in vitro and
      in xenograft models in vivo for colon cancer.
AB  - Interferon (IFN)-lambda1, as a newly identified IFN, interacts with the
      structurally unique IFN-lambda1 receptor complex and exhibits antiviral and
      antiproliferation effects. The major focus of our work was to study the antitumor
      activities of recombinant human IFN-lambda1 (rhIFN-lambda1) in vivo and in vitro.
      The MTT analysis showed that rhIFN-lambda1 inhibited the proliferation of HCT116
      cells in a dose-dependent manner, but with a less efficacy in HT29 cells than
      HCT116 cells. IFN-lambda1 also activated the STATs and induced apoptosis in both
      types of cells. In the in vivo study, we found that rhIFN-lambda1 suppressed
      tumor growth in a dose-dependent fashion, with an inhibition rate of 52% of
      HCT116 (P<0.01) and 56% of HT29 (P<0.01). These results indicate that rhIFN
      lambda1 could be a new potential IFN reagent for cancer therapy.

PMID- 21872389
TI  - Augmented therapeutic efficacy of irinotecan is associated with enhanced drug
      accumulation.
AB  - The goal of this study is to determine whether treatment with
      methylselenocysteine (MSC) results in differential uptake of irinotecan and its
      active metabolite (SN-38) between tumors of head and neck squamous cell
      carcinomas and normal tissue. The in vivo synergy between MSC and irinotecan is
      influenced by treatment schedule and associated with enhancement of tumor vessel
      maturation, intra-tumor concentration of SN-38 and apoptotic death of tumor
      cells. Normal tissue drug concentrations were not impacted by selenium treatment.
      The finding is of clinical relevance for enabling the delivery of higher doses of
      irinotecan to reverse tumor resistance, recurrence and ultimately enhancing cure
      rates.

PMID- 21872390
TI  - Vacuum pyrolysis and hydrometallurgical process for the recovery of valuable
      metals from spent lithium-ion batteries.
AB  - Spent lithium-ion batteries contain lots of strategic resources such as cobalt
      and lithium together with other hazardous materials, which are considered as an
      attractive secondary resource and environmental contaminant. In this work, a
      novel process involving vacuum pyrolysis and hydrometallurgical technique was
      developed for the combined recovery of cobalt and lithium from spent lithium-ion
      batteries. The results of vacuum pyrolysis of cathode material showed that the
      cathode powder composing of LiCoO(2) and CoO peeled completely from aluminum
      foils under the following experimental conditions: temperature of 600 degrees C,
      vacuum evaporation time of 30 min, and residual gas pressure of 1.0 kPa. Over 99%
      of cobalt and lithium could be recovered from peeled cobalt lithium oxides with
      2M sulfuric acid leaching solution at 80 degrees C and solid/liquid ratio of 50 g
      L(-1) for 60 min. This technology offers an efficient way to recycle valuable
      materials from spent lithium-ion batteries, and it is feasible to scale up and
      help to reduce the environmental pollution of spent lithium-ion batteries.

PMID- 21872391
TI  - The protective effect of flaxseed oil on lead acetate-induced renal toxicity in
      rats.
AB  - Lead is a toxic metal inducing many destructive effects leading to a broad range
      of physiological, biochemical, and neurological dysfunctions in humans. Here, we
      investigated the effects of flaxseed oil (1000 mg/kg) on the outcome of renal
      cytotoxicity induced by lead acetate (20mg/kg) in male rats. Lead induced injury
      of the renal tissue. This was evidenced (i) as increases in lead concentration in
      the kidney, (ii) as increases in the histopathological damage of the renal
      tissue, (iii) as increases in uric acid, urea and creatinine, (iv) as increases
      in lipid peroxidation, nitric oxide and reactive oxygen species, and (v) as
      lowered glutathione levels and decreased activities of catalase and superoxide
      dismutase, glutathione reductase, glutathione-S-transferase, and glutathione
      peroxidase, respectively. All these lead-induced parameters were significantly
      altered during flaxseed oil treatment. Therefore, our study suggests the role of
      flaxseed oil in limiting renal cytotoxicity-induced by lead acetate as a model
      for lead toxicity.

PMID- 21872392
TI  - Intratracheal administration of fullerene nanoparticles activates splenic CD11b+
      cells.
AB  - Fullerene nanoparticles ("Fullerenes"), which are now widely used materials in
      daily life, have been demonstrated to induce elevated pulmonary inflammation in
      several animal models; however, the effects of fullerenes on the immune system
      are not fully understood. In the present study, mice received fullerenes
      intratracheally and were sacrificed at days 1, 6 and 42. Mice that received
      fullerenes exhibited increased proliferation of splenocytes and increased splenic
      production of IL-2 and TNF-alpha. Changes in the spleen in response to fullerene
      treatment occurred at different time-points than in the lung tissue. Furthermore,
      fullerenes induced CDK2 expression and activated NF-kappaB and NFAT in
      splenocytes at 6 days post-administration. Finally, CD11b(+) cells were
      demonstrated to function as responder cells to fullerene administration in the
      splenic inflammatory process. Taken together, in addition to the effects on
      pulmonary responses, fullerenes also modulate the immune system.

PMID- 21872393
TI  - The bioreactivity of the sub-10 MUm component of volcanic ash: Soufriere Hills
      volcano, Montserrat.
AB  - With the recent eruption of the Icelandic volcano Eyafallajokull and resulting
      ash cloud over much of Europe there was considerable concern about possible
      respiratory hazards. Volcanic ash can contain minerals that are known human
      respiratory health hazards such as cristobalite. Short-term ash exposures can
      cause skin sores, respiratory and ocular irritations and exacerbation of pre
      existing lung conditions such as asthma. Long-term occupational level exposures
      to crystalline silicon dioxide can cause lung inflammation, oedema, fibrosis and
      cancer. The potential health effects would be dependent on factors including
      mineralogy, surface chemistry, size, and levels and duration of exposure. Bulk
      ash from the Soufriere Hills volcano was sourced and inhalable (<2.5 MUm) ash
      samples prepared and physicochemically characterised. The fine ash samples were
      tested for bioreactivity by SDS-PAGE which determined the strength of binding
      between mineral grains and lung proteins. Selected proteins bound tightly to
      cristobalite, and bound loosely to other ash components. A positive correlation
      was seen between the amount of SiO(2) in the sample and the strength of the
      binding. The strength of binding is a function of the mineral's bioreactivity,
      and therefore, a potential geo-biomarker of respiratory risk.

PMID- 21872394
TI  - Solar photoelectro-Fenton degradation of the herbicide 4-chloro-2
      methylphenoxyacetic acid optimized by response surface methodology.
AB  - A central composite rotatable design and response surface methodology (RSM) were
      used to optimize the experimental variables of the solar photoelectro-Fenton
      (SPEF) treatment of the herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA). The
      experiments were made with a flow plant containing a Pt/air-diffusion reactor
      coupled to a solar compound parabolic collector (CPC) under recirculation of 10 L
      of 186 mg L(-1) MCPA solutions in 0.05 M Na(2)SO(4) at a liquid flow rate of 180
      L h(-1) with an average UV irradiation intensity of about 32 Wm(-2). The optimum
      variables found for the SPEF process were 5.0 A, 1.0mM Fe(2+) and pH 3.0 after
      120 min of electrolysis. Under these conditions, 75% of mineralization with 71%
      of current efficiency and 87.7 k Wh kg(-1) TOC of energy consumption were
      obtained. MCPA decayed under the attack of generated hydroxyl radicals following
      a pseudo-first-order kinetics. Hydroxyl radicals also destroyed 4-chloro-2
      methylphenol, methylhydroquinone and methyl-p-benzoquinone detected as aromatic
      by-products. Glycolic, maleic, fumaric, malic, succinic, tartronic, oxalic and
      formic acids were identified as generated carboxylic acids, which form Fe(III)
      complexes that are quickly photodecarboxylated by the UV irradiation of sunlight
      at the CPC photoreactor. A reaction sequence for the SPEF degradation of MCPA was
      proposed.

PMID- 21872395
TI  - Removing aromatic and oxygenated VOCs from polluted air stream using Pt-carbon
      aerogels: assessment of their performance as adsorbents and combustion catalysts.
AB  - Two series of Pt-catalysts were prepared by impregnation or doping of carbon
      aerogels and different porous textures and Pt-dispersion were obtained. The
      performance of the samples in the elimination of organic compounds (VOCs) by
      adsorption and catalytic combustion was studied and compared with the
      characteristics of both the VOCs and the catalysts and the interactions between
      them. Toluene, xylenes and acetone were selected as representative aromatic or
      oxygenated VOCs. The adsorption of VOCs is favoured at room temperature in the
      case of meso/microporous materials, but at the higher catalytic reaction
      temperature, the micropores volume is more important. Adsorption and catalytic
      combustion occur simultaneously, and are both dependent on temperature, albeit in
      opposite directions. The combustion of aromatic compounds takes place at a lower
      temperature than that required for acetone combustion, so favouring the
      accumulation of adsorbed VOC, something that should be avoided to minimize risks.
      Catalytic performance improves with the contact time and is independent of oxygen
      content above 5% v/v, but declines significantly below this limit.

PMID- 21872396
TI  - Optimization of complex conditions by response surface methodology for APAM
      oil/water emulsion removal from aqua solutions using nano-sized TiO2/Al2O3 PVDF
      ultrafiltration membrane.
AB  - This paper studies the cumulative effect of various parameters, namely anionic
      polyacrylamide (APAM) concentration, oil concentration, pH, trans-membrane
      pressure (TMP), and total dissolved solid (TDS), and obtains optimal parameters
      for the minimum relative flux (J/J(0)) declining in aqueous solutions with
      response surface methodology (RSM). In order to analyze the mutual interaction
      and optimal values of parameters affecting ultrafiltration, a central composite
      rotatable design (CCRD), one method of RSM, was employed. The analysis of
      variance (ANOVA) of the cubic polynomial model demonstrated that this model was
      highly significant and reliable. The results show that the effect of APAM and oil
      on J/J(0) has an inverse trend with pH value increasing. Moreover, the mutual
      interaction of initial APAM (oil) concentration (C(APAM(oil))) and pH (TMP) were
      negligible, while the mutual interaction of C(APAM) and C(oil) has an obvious
      effect, i.e. the effect of initial feed C(APAM) became more important at higher
      values of initial feed C(oil), and the J/J(0) was only about 4%. The favorable
      operate conditions in this ultrafiltration process were at low C(APAM), C(oil),
      pH, and TMP, which agreed with the conclusions of many authors, while considering
      water production, C(APAM) and C(oil) < 50 mg/L, pH < 4, and TMP < 0.075 MPa could
      be accepted.

PMID- 21872397
TI  - Oxidation by-products and ecotoxicity assessment during the photodegradation of
      fenofibric acid in aqueous solution with UV and UV/H2O2.
AB  - The degradation of an aqueous solution of fenofibric acid was investigated using
      ultraviolet (UV) photolysis and UV/H(2)O(2) with a low-pressure mercury lamp. We
      obtained quantum yields at different temperatures and the rate constant for the
      reaction of fenofibric acid with hydroxyl radicals. The maximum radical exposure
      per fluence ratio obtained was 1.4 * 10(-10)ML(-1)mW(-1). Several reaction
      intermediates were detected by means of exact mass measurements performed by
      liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC
      ESI-QTOF-MS). UV and UV/H(2)O(2) pathways involve the decarboxylation of
      fenofibric acid to 4-chloro-4'-(1-hydroxy-1-methylethyl)benzophenone and other
      minor products, predominantly chlorinated aromatics. We detected several
      intermediates from reactions with hydroxyl radicals and some lower molecular
      weight products from the scission of the carbonyl carbon-to-aromatic-carbon bond.
      We recorded high toxicity in UV irradiated samples for the growth of
      Pseudokirchneriella subcapitata even after the total depletion of fenofibric
      acid; this was probably due to the presence of chlorinated aromatics. A degree of
      toxicity reappeared in highly irradiated UV/H(2)O(2) samples, probably because of
      the formation of ring-opening products. The degree of mineralization was closely
      related to that of dechlorination and reached values of over 50% after 3-4 min
      before stabilizing thereafter.

PMID- 21872398
TI  - The recycling of Mn-Zn ferrite wastes through a hydrometallurgical route.
AB  - A novel recycling route using acid leaching, reduction, purification, co
      precipitation and traditional ceramic process was applied to process the Mn-Zn
      ferrite wastes and prepare the corresponding high permeability soft magnetic
      product. Above 95% of Fe, Mn, Zn in the waste materials could be recycled in the
      form of Mn-Zn ferrite products through the hydrometallurgical route. The
      comprehensive properties of Mn-Zn ferrite prepared from wastes by this route have
      broader frequency characteristics, higher resistivity, lower loss coefficient and
      temperature coefficient as compared to the A102 product (Acme Electronics
      Corporation, Taiwan). Moreover, the cost of this recycling technology has
      economical advantage over the traditional ceramic process, which holds a
      promising industrial application.

PMID- 21872399
TI  - Potentiation of triclabendazole action in vivo against a triclabendazole
      resistant isolate of Fasciola hepatica following its co-administration with the
      metabolic inhibitor, ketoconazole.
AB  - An in vivo study in the laboratory rat model has been carried out to monitor
      morphological changes in adult Fasciola hepatica over a 4-day period resulting
      from co-treatment with triclabendazole (TCBZ) and ketoconazole (KTZ), a
      cytochrome P450 inhibitor. Rats were infected with the triclabendazole-resistant
      Oberon isolate of F. hepatica, dosed orally with triclabendazole at a dosage of
      10mg/kg live weight and ketoconazole at a dosage of 10mg/kg live weight. Flukes
      were recovered at 24, 48, 72 and 96 h post-treatment (p.t.) and changes to fluke
      ultrastructure were assessed using transmission electron microscopy (TEM).
      Results showed an increase in the severity of changes to the fluke ultrastructure
      with time p.t. Swelling of the basal infolds and the associated
      mucopolysaccharide masses became more severe with time. Golgi complexes, if
      present, were greatly reduced in size and number by 96 h p.t., and sub-tegumental
      flooding was seen from the 72 h time-period onwards. Some sloughing of the
      tegumental covering over the spines was observed at 96 h p.t. The results
      demonstrated that the Oberon isolate is more sensitive to TCBZ action in the
      presence of KTZ than to TCBZ alone, reinforcing the idea that altered drug
      metabolism is involved in the resistance mechanism. Moreover, they support the
      concept that TCBZ+inhibitor combinations (aimed at altering drug pharmacokinetics
      and potentiating the action of TCBZ) could be used in the treatment of TCBZ-R
      populations of F. hepatica.

PMID- 21872400
TI  - Comparing rich and poor: burn prevention in Wales, Pakistan, India, Botswana and
      Zambia.
AB  - BACKGROUND: Worldwide, over 95% of fire-related burns occur in 'low and middle
      income countries' (LMIC) [1]. The majority of research, investment and expertise
      into the prevention and treatment of burns occurs in high income countries (HIC)
      [2]. Bearing that in mind, this study was conducted in four different LMIC and
      one HIC, with a view to comparing the knowledge of, and previous exposure to,
      burn prevention and first aid. METHODS: A 25 question survey was devised at the
      Welsh Centre for Burns and Plastics, Morriston Hospital, Swansea, to ascertain
      the knowledge, attitude, and practice of individuals in five countries, in
      relation to burns. Overall 1146 participants took part in the survey: 191 from
      Botswana, 492 from India, 198 from Pakistan, 196 from Wales and 69 from Zambia.
      RESULTS: The results show a disparity between the UK and the four LMIC. A higher
      proportion of those in the UK received information on prevention and on first aid
      (51.4% vs. 38.1% and 70.9% vs. 40.1%, respectively). In addition, more of those
      questioned in the UK were able to identify the correct course of action should
      their clothing catch fire or should they spill hot oil on their arm (54.1% vs.
      24.9% and 75% vs. 25.9%, respectively). CONCLUSION: The results show a
      discrepancy in the first aid provision, and level of education about burn
      prevention between a HIC and four LMIC. In addition they suggest an association
      between an increase in knowledge with better practice in relation to burn
      prevention and first aid.

PMID- 21872401
TI  - Utilizing reliable and clinically significant change criteria to assess for the
      development of depression during smoking cessation treatment: the importance of
      tracking idiographic change.
AB  - Studies typically measure mood changes during smoking cessation treatment in two
      ways: (a) by tracking mean change in depression scores or (b) by tracking the
      incidence of major depression development using diagnostic assessments. However,
      tracking mean change does not capture variability in individual mood
      trajectories, and diagnosing participants at multiple time points is time and
      labor intensive. The current study proposes a method of assessing meaningful
      increases in depression without the use of diagnostic assessments by utilizing
      reliable and clinically significant change criteria. This method was applied to
      212 participants in a smoking cessation trial to explore the relationship between
      smoking status and depressed mood, assessed at baseline, end-of-treatment, and 2
      , 6-, and 12-month follow-ups. High rates of reliable (24-28%) and both reliable
      and clinically significant increases (23-24%) in depressed mood were observed
      across all participants, regardless of whether or not they achieved abstinence.
      However, when we calculated group mean change in depression during the trial,
      only decreases in depressed mood where observed across several intervals.
      Findings indicate that utilizing reliable and clinically significant change
      criteria to track symptoms of depression during smoking cessation treatment leads
      to different conclusions than simply tracking mean changes. We propose that a
      combination of reliable and clinically significant change criteria may serve as a
      useful proxy measure for the development of major depressive disorder during
      smoking cessation.

PMID- 21872402
TI  - Social network influences of alcohol and marijuana cognitive associations.
AB  - Decision-making is a social process whereby behaviors are often driven by social
      influences and social consequences. Research shows that social context also plays
      an integral role in decision-making processes. In particular, evidence suggests
      that implicit or non-conscious cognitions are linked to social information in
      memory and that implicit attitudes can be communicated and assimilated between
      people on an unconscious level. This study assesses social contagion of implicit
      cognitions regarding alcohol and marijuana among high school friend networks.
      Data are from an evidence-based drug education program delivered by either a
      health educator or by nominated class leaders over a 3-month period. Implicit
      attitudes were found to be susceptible to social influences, particularly for
      alcohol. Surprisingly, social contagion was stronger for cognitions than for
      behaviors. In addition, results support prior research that has found that
      implicit attitudes are not entirely stable and may be more susceptible to change
      than are behaviors. Public health initiatives to engender behavioral change could
      be facilitated by targeting flexible cognitive associations within existing
      social network structures.

PMID- 21872403
TI  - Arrested blood flow during false aneurysm formation in the carotid arteries of
      cattle slaughtered with and without stunning.
AB  - The time to onset of arrested blood flow and the size of false aneurysms in the
      severed carotid arteries were assessed in 126 cattle during halal slaughter
      without stunning. Thirty six cattle (29%) showed early arrest of blood flow. In
      6%, both the left and right carotid arteries in the same animal stopped bleeding
      before 60s had elapsed following the neck cut. The time to early arrested blood
      flow was on average 21s, and this was accompanied by enlargement with false
      aneurysms which occluded the arteries. In the arteries which were still bleeding
      at 60s after the neck was cut the artery size was normal. Based on comparative
      data from different slaughter premises it appeared that making the cut in the
      neck at the first cervical vertebra instead of the second to fourth cervical
      vertebrae reduced the frequency of false aneurysm formation and early arrested
      blood flow. This was confirmed in a separate controlled trial where 100 cattle
      were stunned with a captive bolt and the arteries were examined following neck
      cutting at either the C1 or C3 positions.

PMID- 21872404
TI  - The biomechanical effect of the distal interosseous membrane on distal radioulnar
      joint stability: a preliminary anatomic study.
AB  - PURPOSE: The distal interosseous membrane (DIOM) is a secondary stabilizer of the
      distal radioulnar joint (DRUJ) and has a considerably variable morphology. The
      purpose of this study was to investigate whether innate DRUJ stability is
      influenced by the anatomic variation of the DIOM. METHODS: Ten fresh-frozen
      cadaver upper extremities were used in this study. The humerus and the ulna were
      affixed rigidly to a custom-made apparatus, with the elbow in 90 degrees  of
      flexion. Testing was performed by translating the radius in volar and dorsal
      directions relative to the ulna, with a 20-N applied force in neutral forearm
      alignment, 60 degrees  pronation, and 60 degrees  supination. Total translation
      of the radius was measured as DRUJ laxity. After the experiment, we investigated
      anatomic variation of the DIOM, especially regarding the existence of the distal
      oblique bundle (DOB), which is a notably thick fiber within the DIOM. We compared
      the DRUJ stability between the groups with and without the DOB. RESULTS: The DOB
      was found in 4 of 10 specimens. The group with a DOB demonstrated a significantly
      greater DRUJ stability in the neutral position than the group without a DOB. In
      pronated and supinated forearm positions, no significant difference in DRUJ
      stability was obtained between the groups with and without a DOB. CONCLUSIONS:
      Innate DRUJ stability in the neutral forearm position was greater in the group
      with a DOB than in those without a DOB. CLINICAL RELEVANCE: This study suggests
      that considerable variation exists in DRUJ laxity and that it partially depends
      on anatomical variations of the DIOM.

PMID- 21872405
TI  - Reverse end-to-side nerve transfer: from animal model to clinical use.
AB  - PURPOSE: Functional recovery after peripheral nerve injury is predominantly
      influenced by time to reinnervation and number of regenerated motor axons. For
      nerve injuries in which incomplete regeneration is anticipated, a reverse end-to
      side (RETS) nerve transfer might be useful to augment the regenerating nerve with
      additional axons and to more quickly reinnervate target muscle. This study
      evaluates the ability of peripheral nerve axons to regenerate across an RETS
      nerve transfer. We present a case report demonstrating its potential clinical
      applicability. METHODS: Thirty-six Lewis rats were randomized into 3 groups. In
      group 1 (negative control), the tibial nerve was transected and prevented from
      regenerating. In group 2 (positive control), the tibial and peroneal nerves were
      transected, and an end-to-end (ETE) nerve transfer was performed. In group 3
      (experimental model), the tibial nerve and peroneal nerves were transected, and
      an RETS nerve transfer was performed between the proximal end of the peroneal
      nerve and the side of the denervated distal tibial stump. Nerve histomorphometry
      and perfused muscle mass were evaluated. Six Thy1-GFP transgenic Sprague Dawley
      rats, expressing green fluorescent protein in their neural tissues, also had the
      RETS procedure for evaluation with confocal microscopy. RESULTS: Nerve
      histomorphometry showed little to no regeneration in chronic denervation animals
      but statistically similar regeneration in ETE and RETS animals at 5 and 10 weeks.
      Muscle mass preservation was similar between ETE and RETS groups by 10 weeks and
      significantly better than negative controls at both time points. Nerve
      regeneration was robust across the RETS coaptation of Thy1-GFP rats by 5 weeks.
      CONCLUSIONS: Axonal regeneration occurs across an RETS coaptation. An RETS nerve
      transfer might augment motor recovery when less-than-optimal recovery is
      otherwise anticipated. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 21872406
TI  - Multicentric giant cell tumor of the upper extremities: 16 years of ongoing
      disease.
AB  - Multicentric giant cell tumor is rare and accounts for less than 1% of all giant
      cell tumors of bone. We describe a case in which all the lesions occurred in the
      upper extremities. The 13-year-old boy's first tumor was in the left index
      metacarpal. Over 16 years, giant cell tumors occurred in 8 sites: right distal
      radius, left lunate, left middle metacarpal, left distal radius, right ring
      finger proximal phalanx, right radial head, left distal humerus, and left
      proximal humerus. Intralesional curettage of the lesions located in the hand and
      carpals was associated with a high incidence of local recurrence, whereas lesions
      in the proximal radius and in the humerus have not recurred.

PMID- 21872407
TI  - The limits of medial femoral condyle corticoperiosteal flaps.
AB  - PURPOSE: The medial femoral condyle (MFC) vascularized corticoperiosteal flap has
      been well described for the treatment of nonunion with minimal bone loss. Recent
      applications of this donor site as a corticocancellous flap for large intercalary
      defects bring into question the vascular territory of bone supplied by the
      descending genicular artery (DGA). This study's purpose is to delineate the
      proximal extent of periosteal blood supply of the medial column of the femur
      provided by the DGA system. METHODS: In 18 cadaveric specimens, the DGA was
      isolated, measured, and cannulated. Using subtraction techniques of fluoroscopic
      angiography, the vascular network and proximal-most extent of periosteal
      perfusion were recorded using radiopaque contrast dye. RESULTS: The DGA branched
      from the superficial femoral artery 14.2 +/- 2.4 cm proximal to the joint line of
      the knee. The length of the vascular pedicle to its attachment onto the
      periosteum was 7.7 +/- 2.2 cm. All specimens demonstrated a filigree of
      periosteal vessels dominated by a transverse and a longitudinal branch at the
      level of the condyle. Proximal perfusion was consistently noted by a large,
      longitudinal medial metaphyseal periosteal artery. The medial metaphyseal
      periosteal artery demonstrated that the proximal-most perfusion of the DGA was
      13.7 +/- 1.3 cm proximal to the joint line. Average femur length was 47.1 +/- 3.1
      cm. The DGA provided perfusion of 29% +/- 2% of the total length of the medial
      femur. CONCLUSIONS: The DGA provides a large and reliable region of periosteal
      perfusion, suggesting that corticocancellous MFC harvest might provide the
      benefits of vascularized bone for large, intercalary nonunion defects
      conventionally treated with fibula flaps. CLINICAL RELEVANCE: Harvest of MFC
      osseous flaps extending up to 13.7 cm proximal to the joint line can be perfused
      from the DGA pedicle. The MFC donor site might, therefore, be a reliable option
      for vascularized reconstruction of larger bone defects.

PMID- 21872408
TI  - Virulence determinants, phylogenetic groups and fluoroquinolone resistance in
      Escherichia coli isolated from cystitis and pyelonephritis.
AB  - AIM OF THE STUDY: The aim of this study is to assess the relation between
      virulence genotype, phylogenetic group and susceptibility to fluoroquinolones and
      the urinary tract infection type including pyelonephritis and cystitis due to
      Escherichia coli. MATERIALS AND METHODS: Between 2006 and 2007, 129 non-duplicate
      E. coli isolates from pyelonephritis (n=56) and cystitis (n=73) were
      prospectively collected. The antibiotic susceptibility was done by disk diffusion
      method. The phylogenetic groups, A, B1, B2 and D and 18 virulence genes were
      determined by multiplex PCR. Statistical analysis was done with the Pearson chi2
      test, Mann-Whitney U-test, Kruskal-Wallis test and stepwise multivariable
      logistic regression analysis, P values below 0.05 were considered statistically
      significant. RESULTS: For the pyelonephritis group, sex ratio was 0.3, the median
      age for women was 30 years and for men it was 54 years. For the cystitis group,
      sex ratio was 0.4, the median age for women was 41.5 years and for men it was
      67.8 years. Significant statistical correlations were found between
      pyelonephritis isolates and susceptibility to ciprofloxacin (P=4 10(-5)), papG
      allele II (P=2 10(-6)), hlyA (P=10(-03)), iroN (P=0.04), iha (P=0.03) and ompT
      (P=0.03) virulence genes, high virulence score (P=0.008) and B2 phylogenetic
      group (P=0.03). In multivariate logistic regression analysis, papG II as
      predictor of pyelonephritis, no correlation could be established for the cystitis
      group. CONCLUSION: Our findings argue for a direct link between pyelonephritis,
      virulence factors, susceptibility to fluroquinolones and B2 phylogenetic group
      among uropthogenic E. coli.

PMID- 21872409
TI  - The role of white matter damage in late onset bipolar disorder.
AB  - Bipolar disorder in elderly is probably heterogenous and the age of onset has
      been considered to be a potential clinical marker of heterogeneity for this
      disease. Early- and late-onset bipolar disorders share symptoms, but it is not
      clear whether they have different aetiologies and vulnerabilities. In bipolar
      disorder one of the most frequent neuroimaging finding is the white matter
      hyperintensities (WMHs). The disruption caused by WMHs in the connectivity
      between structures related to mood regulation and cognition in elderly may be
      responsible for the affective symptomatology seen in these patients. White matter
      hyperintensities are found both in late onset patients and in early age onset
      bipolar patients. It is likely that the aetiology of the white matter
      hyperintensities in late-onset bipolar disorder be multifactorial, although
      cardiovascular changes in particular seem to contribute to their physiopathology.
      In early life onset the aetiology of these lesions is less clear, although
      probably genetic factors are more important than cardiovascular factors.
      Understanding the aetiopathogenesis is of key importance when dealing with this
      disease.

PMID- 21872410
TI  - Unexpected natural death secondary to intra-abdominal bleeding: report of one
      idiopathic spontaneous intraperitoneal hemorrhage case.
AB  - A 39-year-old woman was found dead at home. She was single, foreign national,
      chronic alcoholic, and had given shelter to a compatriot for three days. This man
      found the deceased in her bed, after a night of heavy drinking. The emergency
      medical team observed numerous recent blue ecchymoses of the upper limbs. Because
      of the unclear circumstances, a medicolegal autopsy was ordered by the public
      prosecutor. Massive hemoperitoneum was diagnosed with no visible internal
      traumatic injury. Autopsy revealed hepatic and pancreatic abnormalities secondary
      to chronic alcoholism, which were confirmed by pathological study. The source of
      the hemoperitoneum was not identified despite careful visceral and vascular
      examination. The authors concluded that death was secondary to idiopathic
      spontaneous hemoperitoneum or abdominal apoplexy. The forensic literature on
      unexpected death due to massive nontraumatic intra-abdominal hemorrhage in
      association with liver cirrhosis is sparse, with only five cases reported,
      including the present case.

PMID- 21872411
TI  - Surgical treatment for congenital absence of the oval window with facial nerve
      anomalies.
AB  - Three patients with a middle ear malformation characterized by the absence of the
      oval window and complicated by facial nerve anomalies were treated by surgery.
      Hearing ability of all the patients was improved. A variety of facial nerve
      anomalies were observed. Fenestration of the vestibule above the facial nerve was
      performed in the case of 2 of the 3 patients. In the other patient, fenestration
      of the scala vestibuli below the facial nerve was performed. In the case of all
      the 3 patients, hearing ability improved after the surgery and remained stable
      for a long time. Surgery for this disease has been considered difficult because
      of a high risk of complications. Because all the 3 patients showed excellent long
      term surgical results, we suggest that fenestration of the inner ear should be
      considered one of the main options for the management and treatment of an absent
      oval window associated with facial nerve anomalies.

PMID- 21872412
TI  - Treatment assessment based on computerized lymph node volume and ratio of
      necrotic area in tuberculous cervical lymphadenitis.
AB  - OBJECTIVE: The objective of this study was to investigate the feasibility of
      computerized segmentation of lymph nodes to evaluate the relationship of
      treatment outcomes in tuberculous cervical lymphadenitis (TCL). METHODS: The
      study included 52 subjects with TCL that had CT before standard medical
      treatment. The relationship between the medication treatment response, volume and
      ratio of necrotic area of the largest lymph node in patients with TCL was
      evaluated. The treatment outcome was defined as the 'responder' (n=35) and 'non
      responder' (n=17) groups. Seventeen non-responder patients required surgery.
      RESULTS: The average lymph node volumes and ratio of necrotic area were
      58.59cm(3) (range, 4.96-249.48cm(3)) and 0.30 (range, 0-0.59), respectively.
      There was a significant difference in the lymph node volumes (34.91+/-24.00cm(3)
      vs. 107.04+/-69.12cm(3), p<0.001) and ratio of necrotic area (0.26+/-0.12 vs.
      0.40+/-0.14, p=0.001) between responders and non-responders. The receiver
      operating-characteristic (ROC) curve analysis was used for differentiating
      responders from non-responders; it showed that the area under the curve for the
      lymph node volumes and ratio of necrotic area was 0.845 and 0.759, respectively.
      The cut-off value for the lymph node volumes and ratio of necrotic area was
      44.15cm(3) and 0.36 based on the ROC curve. CONCLUSIONS: A large lymph node
      volume and high ratio of necrotic area on the 3D reconstruction of CT images were
      associated with the response to medical treatment for TB. These findings might be
      useful for assessing treatment outcomes.

PMID- 21872413
TI  - Three-phase hollow fiber liquid-phase microextraction based on two immiscible
      organic solvents for determination of tramadol in urine and plasma samples.
AB  - Recently, the new concept of three-phase liquid microextraction was introduced
      based on applying two immiscible organic solvents in lumen and wall pores of
      hollow fiber. In the present work, this novel microextraction technique combined
      with gas chromatography-mass spectrometry has been developed for determination of
      tramadol, an analgesic agent, in plasma and urine samples. A systematic
      investigation of the proposed method was applied to find optimal extraction
      conditions and evaluate the interaction effects between the factors by designing
      experiments according to the methodology of Box-Behnken response surface design.
      Analysis of variance (ANOVA) revealed that the important factors contributing to
      extraction efficiency are extraction time, stirring rate and hollow fiber length.
      Under the optimum conditions, the developed method provided a preconcentration
      factor of 546, good repeatability (RSD %=6.4), and good linearity (r(2)=0.995)
      for spiked plasma and urine real samples. The linear dynamic range from 0.1 to
      400 MUg L(-1) and limit of detection (LOD) of 0.08 MUg L(-1) were obtained under
      selected ion monitoring mode. The results demonstrated that three-phase hollow
      fiber microextraction based on two immiscible solvents is a simple and accurate
      technique with very good preconcentration factor and clean-up for extraction of
      tramadol from biological samples.

PMID- 21872414
TI  - Quantification of tamoxifen and three of its phase-I metabolites in human plasma
      by liquid chromatography/triple-quadrupole mass spectrometry.
AB  - In view of future pharmacokinetic studies, a highly sensitive ultra performance
      liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method has been
      developed for the simultaneous quantification of tamoxifen and three of its main
      phase I metabolites in human lithium heparinized plasma. The analytical method
      has been thoroughly validated in agreement with FDA recommendations. Plasma
      samples of 200 MUl were purified by liquid-liquid extraction with 1 ml n
      hexane/isopropanol, after deproteination through addition of 50 MUl acetone and
      50 MUl deuterated internal standards in acetonitrile. Tamoxifen, N-desmethyl
      tamoxifen, 4-hydroxy-tamoxifen and endoxifen were chromatographically separated
      on an Acquity UPLC((r)) BEH C18 1.7 MUm 2.1 mm*100 mm column eluted at a flow
      rate of 0.300 ml/min on a gradient of 0.2mM ammonium formate and acetonitrile,
      both acidified with 0.1% formic acid. The overall run time of the method was 10
      min, with elution times of 2.9, 3.0, 4.1 and 4.2 min for endoxifen, 4-hydroxy
      tamoxifen, N-desmethyl-tamoxifen and tamoxifen, respectively. Tamoxifen and its
      metabolites were quantified by triple-quadrupole mass spectrometry in the
      positive ion electrospray ionization mode. The multiple reaction monitoring
      transitions were set at 372>72 (m/z) for tamoxifen, 358>58 (m/z) for N-desmethyl
      tamoxifen, 388>72 (m/z) for 4-hydroxy-tamoxifen and 374>58 (m/z) for endoxifen.
      The analytical method was highly sensitive with the lower limit of quantification
      validated at 5.00 nM for tamoxifen and N-desmethyl-tamoxifen and 0.500 nM for 4
      hydroxy-tamoxifen and endoxifen, which is equivalent to 1.86, 1.78, 0.194 and
      0.187 ng/ml for tamoxifen, N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and
      endoxifen, respectively. The method was also precise and accurate, with within
      run and between-run precisions within 12.0% and accuracy ranging from 89.5 to
      105.3%. The method has been applied to samples from a clinical study and cross
      validated with a validated LC-MS/MS method in serum.

PMID- 21872415
TI  - Analytical methods for determination of magnoflorine and saponins from roots of
      Caulophyllum thalictroides (L.) Michx. using UPLC, HPLC and HPTLC.
AB  - Analytical methods including HPLC, UPLC and HPTLC are presented for the
      determination of major alkaloid and triterpene saponins from the roots of
      Caulophyllum thalictroides (L.) Michx. (blue cohosh) and dietary supplements
      claiming to contain blue cohosh. A separation by LC was achieved using a reversed
      phase column, PDA with ELS detection, and ammonium acetate/acetonitrile gradient
      as the mobile phase. Owing to their low UV absorption, the triterpene saponins
      were detected by evaporative light scattering. The eight triterpene saponins
      (cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C,
      cauloside A and saponin PE) and the alkaloid magnoflorine could be separated
      within 35 min using HPLC method and within 8.0 min using UPLC method with
      detection limits of 10 MUg/mL for saponins and 1 MUg/mL for magnoflorine. The
      detection wavelength was 320 nm for magnoflorine and ELS detection was used for
      the eight saponins. The methods were also successfully applied to analyze
      different dietary supplements. For the products claiming to contain blue cohosh,
      there was a significant variability in the amounts of triterpene saponins
      detected. Calculations based on the analysis results for dietary supplements
      showed that maximum daily intake of alkaloid and saponins vary with the form
      (solids/liquids) and recommended doses according to the products label. Intakes
      varied from 0.57 to 15.8 mg/day for magnoflorine and from 5.97 to 302.4 mg/day
      for total saponins. LC-mass spectrometry coupled with electrospray ionization
      (ESI) method is described for the identification and confirmation of nine
      compounds in plant samples and dietary products. A HPTLC method was also
      developed for the fast chemical fingerprint analysis of C. thalictroides samples.

PMID- 21872416
TI  - Screening medicinal plants for the detection of novel antimalarial products
      applying the inhibition of beta-hematin formation.
AB  - The identification of novel scaffolds for the development of effective and safe
      treatments to fight malaria is urgently needed. One of the main opportunities is
      the discovery of new molecules from natural origin. A simple, robust and cost
      effective colorimetric assay based on the inhibition of beta-hematin has been
      adapted to routinely screen plant extracts with the ultimate goal to identify
      novel antimalarial ingredients. The development of this assay has included a
      careful optimization of all critical experimental parameters. The beta-hematin
      assay can be completed in less than one working day, requiring a 96-well UV-vis
      plate reader and low-cost commercially available reagents using a standard
      operating protocol. It can be used on its own or in combination with the well
      known Plasmodium growth inhibition assay and has the obvious merit to be
      informative at the early stage of drug discovery regarding the mechanism of
      action of the actives. A total of 40 diverse natural products and 219 plants
      extracts were tested. Good correlations in respect with specificity (pure
      compounds 85%, extracts 93%) and positive predictive value (pure compounds 72%,
      extracts 50%) were obtained in comparison with Plasmodium growth inhibition assay
      that was used as the reference assay.

PMID- 21872417
TI  - Differential effects of Cu(II) and Fe(III) on the binding of omeprazole and
      pantoprazole to bovine serum albumin: toxic effect of metal ions on drugs.
AB  - The interaction between omeprazole or pantoprazole and bovine serum albumin (BSA)
      has been investigated in the absence and presence of Cu(II) or Fe(III) by means
      of fluorescence spectroscopy. The fluorescence intensity of BSA decreased
      remarkably with slight blue shifts by adding omeprazole or pantoprazole. Similar
      blue shifts and fluorescence shape with larger quenching extent of BSA were
      observed with increasing concentrations of omeprazole or pantoprazole in the
      presence of Cu(II) or Fe(III). The presence of Cu(II) and Fe(III) increased the
      affinities of omeprazole with BSA about 12.0% and 3.9%, while the presence of
      Cu(II) decreased the affinity of pantoprazole with BSA about 25.7%, and the
      presence of Fe(III) improved the affinity of pantoprazole with BSA about 16.3%.
      The changeable affinity and increased binding distance in the presence of metal
      ions may result from a noncompetitive binding in different albumin sites. The
      results indicated that the structures of omeprazole or pantoprazole and kinds of
      metal ions together affected the binding interaction with BSA, which may have
      relevant consequence in rationalizing dosage for patients with gastric ulcer.

PMID- 21872419
TI  - Impact of cilostazol after endovascular treatment for infrainguinal disease in
      patients with critical limb ischemia.
AB  - BACKGROUND: Cilostazol reduces restenosis and repeat revascularization after
      endovascular therapy (EVT) in claudicant patients with femoropopliteal lesions.
      However, the efficacy of cilostazol in patients with critical limb ischemia (CLI)
      is unclear. Therefore, we investigated the effect of cilostazol on outcomes in
      patients with CLI. METHODS: From January 2004 to December 2009, 618 patients
      (30.8% women, 356 treated with cilostazol, 72.4 +/- 7.3 years old) with CLI
      underwent EVT for de novo infrainguinal lesions. Their data were retrospectively
      analyzed. The primary outcome measure was amputation-free survival (AFS), The
      secondary outcome measures were overall survival, limb salvage, freedom from
      repeat revascularization, and freedom from surgical conversion. Mean follow-up
      was 21 +/- 14 months. RESULTS: AFS and the limb salvage rate at 5 years were
      significantly higher in the cilostazol-treated group (47.7% vs 32.7%, P < .01;
      86.6% vs 75.3%, P < .01; respectively). However, overall survival and freedom
      from repeat revascularization at 5 years did not differ significantly between the
      two groups (43.9% vs 46.0%, P = .24; 39.9% vs 31.8%, P = .21, respectively).
      Freedom from surgical conversion at 5 years was significantly higher in the
      cilostazol-treated group (91.0% vs 81.2%, P < .01). After correcting all end
      points with baseline variables, cilostazol was effective for prevention of AFS
      (hazard ratio [HR], 0.67; 95% confidential interval [CI], 0.49-0.91; adjusted P =
      .01) and improvement of limb salvage rate (HR, 0.42; 95% CI, 0.25-0.69; adjusted
      P < .01). There was no significant difference in overall survival, repeat
      revascularization, and surgical conversion between the groups. CONCLUSIONS:
      Cilostazol may improve AFS and limb salvage rate after EVT for infrainguinal
      disease in patients with CLI.

PMID- 21872418
TI  - The influence of early-phase remodeling events on the biomechanical properties of
      engineered vascular tissues.
AB  - OBJECTIVES: During the last decade, the use of ex vivo-derived materials designed
      as implant scaffolds has increased significantly. This is particularly so in the
      area of regenerative medicine, or tissue engineering, where the natural chemical
      and biomechanical properties have been shown to be advantageous. By focusing on
      detailed events that occur during early-phase remodeling processes, our objective
      was to detail progressive changes in graft biomechanics to further our
      understanding of these processes. METHODS: A perfusion bioreactor system and
      acellular human umbilical veins were used as a model three-dimensional vascular
      scaffold on which human myofibroblasts were seeded and cultured under static or
      defined pulsatile conditions. Cell function in relation to graft mechanical
      properties was assessed. RESULTS: Cells doubled in density from approximately 1 *
      10(6) to 2 +/- 0.4 * 10(6) cells/cm ringlet, whereas static cultures remained
      unchanged. The material's compressive stiffness and ultimate tensile strength
      remained unchanged in both static and dynamic systems. However the Young's
      modulus values increased significantly in the physiologic range, whereas in the
      failure range, a significant reduction (66%) was shown under dynamic conditions.
      CONCLUSIONS: As pulse and flow conditions are modulated, complex mechanical
      changes are occurring that modify the elastic modulus differentially in both
      physiologic and failure ranges. Mechanical properties play an important role in
      graft patency, and a dynamic relationship between structure and function occurs
      during graft remodeling. These investigations have shown that as cells migrate
      into this ex vivo scaffold model, significant variation in material elasticity
      occurs that may have important implications in our understanding of early-stage
      vascular remodeling events.

PMID- 21872420
TI  - Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse
      model.
AB  - Sepsis is a major cause of death worldwide. The associated risks and mortality
      are known to significantly increase on exposure to alcohol (chronic or acute).
      The underlying mechanisms of the association of acute ethanol ingestion and poor
      prognosis of sepsis are largely unknown. The study described here was designed to
      determine in detail the role of ethanol and TLR4 in the pathogenesis of the
      sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial
      clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine
      production were evaluated using wild-type and TLR4 hyporesponsive mice treated
      with ethanol and then challenged with a nonpathogenic strain of Escherichia coli.
      Ethanol-treated mice exhibited a decreased clearance of bacteria and produced
      lesser amounts of most pro-inflammatory cytokines in both strains of mice at 2h
      after challenge. Neither ethanol treatment nor a hyporesponsive TLR4 had
      significant effects on the cell numbers in the peritoneal cavity and spleen 2h
      postinfection. The suppressive effect of acute ethanol exposure on cytokine and
      chemokine production was more pronounced in the wild-type mice, but the untreated
      hyporesponsive mice produced less of most cytokines than untreated wild-type
      mice. The major conclusion of this study is that acute ethanol exposure
      suppresses pro-inflammatory cytokine production and that a hyporesponsive TLR4
      (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels, but the cytokines
      and other mediators induced through other receptors are sufficient to ultimately
      clear the infection but not enough to induce lethal septic shock. In addition,
      results reported here demonstrate previously unknown effects of acute ethanol
      exposure on leukemia inhibitory factor and eotaxin, and provide the first
      evidence that interleukin (IL)-9 is induced through TLR4 in vivo.

PMID- 21872421
TI  - Techniques for managing poor quality tissue and bone during arthroscopic rotator
      cuff repair.
AB  - Arthroscopic rotator cuff repair can be challenged by poor soft-tissue or bone
      quality. Both biologic and biomechanical factors have been widely implicated in
      rotator cuff retearing after arthroscopic repair. In this Level V article, we
      describe several techniques for arthroscopically overcoming these challenges.

PMID- 21872422
TI  - The rationale for an arthroscopic approach to shoulder stabilization.
AB  - The gold standard of treatment for glenohumeral instability has traditionally
      been viewed as open shoulder stabilization. With the increased awareness of
      complex instability patterns and the ability to preoperatively detect concomitant
      pathology with advanced imaging modalities, an evidence-based shift to an all
      arthroscopic approach to shoulder stabilization surgery is occurring. Current
      data suggest that patients who meet eligibility criteria for arthroscopic
      stabilization (those without significant bony lesions or significant deformity)
      can expect equivalent rates of recurrence, better functional outcomes, and less
      morbidity. Modern arthroscopic techniques using suture anchors and capsular
      plication have resulted in a significant improvement over previous reports in the
      orthopaedic literature. An argument is put forth on the benefits of an all
      arthroscopic approach to shoulder stabilization in athletes and nonathletes alike
      based on a review of the current orthopaedic literature comparing the evolved
      arthroscopic technique with more traditional open methods.

PMID- 21872423
TI  - Accuracy of intra-articular injection of the glenohumeral joint: a modified
      anterior approach.
AB  - PURPOSE: This study examined the accuracy of our modified anterior approach to
      the glenohumeral joint using arthrography. METHODS: Two hundred fifty-six
      consecutive patients with adhesive capsulitis received the glenohumeral joint
      injection: a mixture of 1 mL of 40 mg of triamcinolone hexacetonide, 2 mL of 2%
      lidocaine, 3 mL of contrast medium (Ioxitalamate), and 4 mL of normal saline
      solution, for a total of 10 mL, through a modified anterior approach.
      Anteroposterior, lateral, and axial arthrography after each injection was
      performed to determine the accuracy and patterns of the injection. The injection
      was judged to be successful if some of the contrast medium was placed within the
      joint. RESULTS: There were 78 male and 178 female patients, and the mean age was
      54 years (range, 28 to 87 years). In 232 of the 256 patients (90.6%), the
      injection was deemed to have reached the glenohumeral joint, and these cases were
      considered successful. Among these patients, the contrast medium was shown only
      in the joint in 189 (73.8%), whereas in 43 (16.8%) it was shown both in and out
      of the joint. Of the 24 misguided injections, 15 (5.9%) had anterior placement, 6
      (2.3%) had posterior placement, and 2 (0.8%) had superior placement, whereas the
      material was located in all portions outside the joint in 1 (0.4%). CONCLUSIONS:
      This study showed that our modified anterior approach had an accuracy greater
      than 90% for the intra-articular injection of the glenohumeral joint without
      radiographic guidance.

PMID- 21872424
TI  - Prospective results of uncemented tantalum monoblock tibia in total knee
      arthroplasty: minimum 5-year follow-up in patients younger than 55 years.
AB  - A significant increase in younger patients undergoing total knee arthroplasty
      raises the theoretical concern for revision secondary to micromotion and fixation
      failure with cemented components. We prospectively studied 100 consecutive
      tantalum monoblock uncemented tibial components and 312 concurrent cemented
      controls. Patients younger than 55 years with adequate bone stock were enrolled.
      This cementless patient group was younger and had higher preoperative functional
      status. Prostheses were posterior-substituting uncemented femoral and tibial
      components with a cemented patellar button. Knee Society pain and function scores
      and radiographs were obtained, and a cost analysis was performed. Knee Society
      scores were excellent and equivalent beyond 6 months. There was no significant
      difference in perioperative blood loss, complication rates, or cost. There was a
      significant decrease in operative time in the uncemented group. Radiographs
      revealed no failures of ingrowth at last follow-up. There were 3 uncemented group
      failures, but none were due to failure of fixation. The use of a porous tantalum
      tibia at minimum 5 years has yielded promising clinical and radiographic results
      in a younger patient population.

PMID- 21872425
TI  - The PRISMA Symposium 2: lessons from beyond Europe. reflections on the evolution
      of palliative care research and policy in Canada.
AB  - In Canada, the aging population with a rising incidence of chronic diseases-and
      thus more complex care needs-is putting significant pressure on the health care
      system, long-term care system, and family caregivers. Ten years ago, the
      Government of Canada appointed Canada's first Minister with Special
      Responsibility for Palliative Care. During that time, the federal government
      developed significant public policy goals for palliative care, including the
      Canadian Strategy on Palliative and End-of-Life Care. This strategy led to many
      policy improvements, particularly in the areas of research and data collection,
      education for health care professionals, and support for caregivers. In 2007, the
      Secretariat within the federal government supporting the Canadian strategy was
      defunded and disbanded. Four years later, progress in improving palliative care
      for Canadians has slowed. This article reviews some of the successes of
      palliative care policy and research in Canada and outlines several lessons to be
      learned for other jurisdictions developing public policy for palliative care.

PMID- 21872426
TI  - Blood transfusion safety in Africa: a literature review of infectious disease and
      organizational challenges.
AB  - Blood safety remains an important public health concern in Africa where lack of
      availability or provision of unsafe blood adversely impacts morbidity and
      mortality in the region. In recognition of this shortfall, the World Health
      Organization (WHO) established a goal of regional blood safety by 2012 through
      improved "organization and management, blood donor recruitment and collection,
      testing of donor blood as well as appropriate clinical use of blood" (Tagny et
      al: Transfusion. 2008;48:1256-1261; Tapko et al: Status of Blood Safety in the
      WHO African Region: Report of the 2006 Survey
      http://www.afro.who.int/en/divisions-a-programmes/dsd/health-technologies-a
      laboratories.html. Brazzaville, Republic of Congo: WHO Regional Office for
      Africa; 2006). Although there has been substantial progress toward meeting these
      objectives, there are continued obstacles to both development and sustainability.
      In a setting where transfusion oversight is still being improved, transfusion
      transmitted infections are of real concern. The high prevalence of some
      transfusion-transmissible agents such as hepatitis B virus and HIV in the general
      population means that some infected blood units escape detection by even well
      performed laboratory testing, resulting in potential downstream transmission to
      patients. The spectrum of transfusion-transmitted infection include conventional
      as well as exotic pathogens, many of which are endemic to the region, thereby
      imparting ongoing challenges to recruitment and testing strategies.

PMID- 21872427
TI  - Improving safety for young blood donors.
AB  - Young blood donors between the ages of 16 and 18 years contribute substantially
      to the blood supply in the United States, accounting for about 14% of the
      allogeneic whole blood collected by the American Red Cross in 2010. However,
      studies have consistently demonstrated that the donors' age, total blood volume,
      and first-time donation status independently contribute to the risk of syncopal
      reactions after whole blood donation. Efforts to improve the donation experience
      are crucial not only to ensure the health and well-being of blood donors but also
      to sustain an adequate blood supply. Even minor reactions or temporary deferrals
      discourage individuals from donating blood again. Shifting population
      demographics and advances in medical care in the United States and other
      countries predict that the need for blood will increase, whereas blood donation
      by the older generations declines each year. Broad deferral strategies and
      precautionary measures have further winnowed the eligible donor pool, but their
      contribution to transfusion safety remains controversial. Consequently, blood
      centers that depend on recruiting and retaining adolescent blood donors have made
      concerted efforts to improve safety, especially on high school blood drives.
      Population-based operational tactics to improve donation safety focus on donor
      education, the drive environment, or recruiting individuals who are less likely
      to have reactions. Physiologic strategies modulate the donors' response to blood
      loss, decreasing their susceptibility to a donation-related reaction. This review
      examines the published data supporting the measures recently taken by blood
      centers to reduce the risk of syncopal reactions among young, whole blood donors.

PMID- 21872428
TI  - Principles and practice of thromboelastography in clinical coagulation management
      and transfusion practice.
AB  - In the recent years, thromboelastography has become a popular monitoring device
      for hemostasis and transfusion management in major surgery, trauma, and
      hemophilia. Thromboelastography is performed in whole blood and assesses the
      viscoelastic property of clot formation under low shear condition.
      Thromboelastography can be performed with a variety of activator and inhibitors
      at different concentrations representing the most important factors for different
      intervals and clot formation variables reported in multiple studies and
      algorithms. Furthermore, fibrinogen levels and platelet counts have a major
      influence on thromboelastographic variables. In addition, differences in patient
      populations, devices, and preanalytical conditions contribute to some conflicting
      findings in different studies.

PMID- 21872429
TI  - Duodenal obstruction from mesenteric stents mimicking SMA syndrome.
AB  - BACKGROUND: Superior mesenteric artery (SMA) syndrome is a rare condition, which
      results in compression of the third portion of the duodenum by a narrow-angled
      SMA against the aorta. We report a case of a patient treated for chronic
      mesenteric ischemia, who developed an SMA-like syndrome as a result of the
      compression of the duodenum between an SMA stent and an inferior mesenteric
      artery (IMA) stent. METHODS AND RESULTS: A 44-year-old woman with chronic
      mesenteric ischemia had previously been treated with multiple endovascular
      stents. She re-presented with persistent abdominal pain and weight loss. Findings
      from the angiogram performed revealed an occluded celiac artery and an SMA.
      Mesenteric perfusion was maintained by the IMA with poor collateralization to the
      celiac circulation. At the time of surgical exploration, there were no suitable
      target sites for a traditional aortomesenteric bypass because of the extensive
      length of prior stenting. A renohepatic bypass with reversed saphenous vein was
      performed to improve the celiac circulation. Postoperatively, she continued to
      have persistent abdominal pain associated with nausea and vomiting. An upper
      gastrointestinal study was performed that revealed severe partial obstruction of
      the third portion of her duodenum. On re-reviewing her preoperative computed
      tomography scan of the abdomen, it was more apparent that the duodenum was
      constricted between the SMA and IMA stents that had been previously placed. She
      underwent re-exploration, and a side-to-side duodenojejunostomy was performed.
      Subsequent study of the upper gastrointestinal showed resolution of the
      obstruction. CONCLUSION: To our knowledge, this is the first report of duodenal
      obstruction caused as a result of the complications caused by multiple stent
      placements, which gave an impression of SMA-like syndrome.

PMID- 21872430
TI  - The antigen specificity of the rheumatoid arthritis-associated ACPA directed to
      citrullinated fibrin is very closely restricted.
AB  - The major targets of the disease-specific autoantibodies to citrullinated
      proteins (ACPA) in synovium of rheumatoid arthritis (RA) patients are borne by
      the citrullinated alpha- and beta-chains of fibrin. We demonstrated that ACPA
      target a limited set of citrullinated fibrin peptides and particularly four
      multicitrullinated peptides which present the major epitopes. In this study, we
      established the clear immunodominance of the peptides alpha36-50Cit(38,42) and
      beta60-74Cit(60,72,74) which were recognised by 51/81 (63%) and 61/81 (75%) of
      ACPA-positive patients, respectively, more than 90% recognising one, the other or
      both peptides. We also identified the citrullyl residues alphaCit(42),
      betaCit(72) and betaCit(74) as essential for antigenicity, and at a lesser degree
      alphaCit(38). Then, we assayed on overlapping 7-mer peptides encompassing the
      sequences of the two peptides, 3 series of sera recognising either alpha36
      50Cit(38,42) or beta60-74Cit(60,72,74) or both peptides. In each series, the
      reactivity profiles of the sera, largely superimposable, allowed identification
      of the two 4/5-mer overlapping epitopes (alpha: VECit(42)HQ and alpha':
      Cit(38)VVE), and the single 5-mer epitope (beta: GYCit(72)ACit(74)), all located
      to a flexible globular domain of fibrin on a topological 3D model. In conclusion,
      we demonstrated that only 3 immunodominant epitopes are targeted by ACPA on
      citrullinated fibrin stressing their actual oligoclonality. However, the
      reactivity to the 3 epitopes distinguishes three subgroups of patients. The
      closely restricted antigen specificity suggests that the autoimmune reaction to
      citrullinated fibrin is antigen-driven. The accessibility of the epitopes
      reinforces the hypothesis of a pathogenic role for ACPA via immune complexe
      formation in the synovial tissue.

PMID- 21872431
TI  - Dietary intake of medium- and long-chain triacylglycerols ameliorates insulin
      resistance in rats fed a high-fat diet.
AB  - OBJECTIVE: Excessive accumulation of visceral fat is strongly associated with
      insulin resistance. The present investigation examined the effects of dietary
      intake of medium- and long-chain triacylglycerols (MLCTs), which have been shown
      to induce significantly lower visceral fat accumulation in rats and humans, on
      high-fat diet-induced obesity and insulin resistance in rats. These effects were
      then compared with those observed in long-chain triacylglycerol (LCT)-fed rats.
      METHODS: After an 8-wk feeding of a high-fat diet, which induced severe whole
      body insulin resistance, male Sprague-Dawley rats were fed a standard diet
      containing LCTs or MLCTs for 6 wk. After the dietary treatment, an oral glucose
      tolerance test was performed. RESULTS: Although body weight and total intra
      abdominal fat mass did not differ between the two groups, mesenteric fat weight
      in the MLCT-fed group was significantly lower than that in the LCT group (P <
      0.05). The increase in plasma insulin concentrations, but not in glucose, after
      glucose administration (area under the curve) was significantly smaller in the
      MLCT group than in the LCT group (P < 0.01) and was significantly associated with
      mesenteric fat weight (P < 0.05). MLCT-fed rats had significantly higher plasma
      adiponectin concentrations compared with LCT rats (P < 0.05). Adiponectin
      concentrations were negatively correlated with the area under the curve for
      plasma insulin (P < 0.05) and tended to be inversely related to mesenteric fat
      weight (P = 0.08). CONCLUSION: These results suggest that dietary intake of MLCTs
      may improve insulin resistance in rats fed a high-fat diet, at least in part
      through increased adiponectin concentrations caused by a lower mesenteric fat
      mass.

PMID- 21872432
TI  - Long-term leucine supplementation reduces fat mass gain without changing body
      protein status of aging rats.
AB  - OBJECTIVE: Aging is characterized by alterations in body composition such as an
      increase in body fat and decreases in muscle mass (sarcopenia) and bone density
      (osteopenia). Leucine supplementation has been shown to acutely stimulate protein
      synthesis and to decrease body fat. However, the long-term effect of consistent
      leucine supplementation is not well defined. This study investigated the effect
      of leucine supplementation during aging. METHODS: Six-month-old rats were divided
      into three groups: an adult group (n = 10) euthanized at 6 mo of age, a leucine
      group (n = 16) that received a diet supplemented with 4% leucine for 40 wk, and a
      control group (n = 19) that received the control diet for 40 wk. The following
      parameters were evaluated: body weight, food intake, chemical carcass
      composition, indicators of acquired chronic diseases, and indicators of protein
      nutritional status. RESULTS: Body weight and fat were lower in the leucine group
      after 40 wk of supplementation compared with the control group but still higher
      than in the adult group. The lipid and glycemic profiles were equally altered in
      the control and leucine groups because of aging. In addition, leucine
      supplementation did not affect the changes in protein status parameters
      associated with aging, such as decreases in body and muscle protein and total
      serum protein. CONCLUSION: The results indicate that leucine supplementation
      attenuates body fat gain during aging but does not affect risk indicators of
      acquired chronic diseases. Furthermore, supplemented animals did not show signs
      of a prevention of the decrease in lean mass associated with aging.

PMID- 21872433
TI  - Malnutrition as an independent predictor of clinical outcome in critically ill
      children.
AB  - OBJECTIVE: To determine the nutritional status of a cohort of children admitted
      to a pediatric intensive care unit (ICU) and to assess the effect of malnutrition
      as an independent risk factor affecting outcome in this patient group. METHODS:
      In a prospective cohort study, 385 children admitted to the ICU of a teaching
      hospital over a 2-y period were assessed for nutritional status at admission and
      clinical outcome. The outcome variables were 30-d mortality, length of ICU stay,
      and length of mechanical ventilation. Potential exposure variables were gender,
      age, diagnosis (clinical versus surgical), septic shock, malnutrition, and scores
      on the Pediatric Index of Mortality and Pediatric Logistic Organ Dysfunction.
      Nutritional status was determined using z scores of weight for age, height for
      age, and body mass index, based on the World Health Organization child growth
      standards. Patients with z score < -2 of anthropometric indexes were considered
      malnourished. RESULTS: 175 patients (45.5%) were malnourished on admission.
      Sixteen patients of the malnourished group (9.14%) and 25 patients (11.9%) of the
      non-malnourished group died. Malnutrition was associated with greater length of
      mechanical ventilation and length of ICU stay, but not with mortality on
      univariate analysis. Malnutrition was associated with greater length of
      ventilation on the multiple logistic regression model (OR 1.76, 95%; CI 1.08
      2.88; P = 0.024). CONCLUSION: Malnutrition is common among children admitted to
      an ICU. This factor was not a predictor of mortality but showed independent
      association with length of mechanical ventilation.

PMID- 21872434
TI  - Elevation of tissue alpha-tocopherol levels by conjugated linoleic acid in
      C57BL/6J mice is not associated with changes in vitamin E absorption or alpha
      carboxyethyl hydroxychroman production.
AB  - OBJECTIVE: Conjugated linoleic acid (CLA) decreases adipose mass and increases
      vitamin E levels in the liver and adipose tissue in mice. The aim of the present
      study was to examine the mechanism by which CLA alters vitamin E levels in
      tissues and antioxidant activity in mice. METHODS: C57BL/6J mice were divided
      into three groups and fed 5% lipid as soybean oil alone (control group), 4%
      soybean oil supplemented with 1% CLA (CLA group), or 5% lipid with a vitamin E
      supplement (VE group) for 4 wk. RESULTS: The CLA and VE diets resulted in a
      significant increase in the alpha-tocopherol concentration in all tissues
      examined, i.e., the liver, kidney, testis, spleen, heart, lung, and adipose
      tissue (P < 0.05). Levels of thiobarbituric acid-reactive substances in the
      kidney, testis, heart, lung, and adipose tissue were lower in the CLA and VE
      groups than in the control group (P < 0.05). CLA did not alter the absorption
      rate of vitamin E or alpha-carboxyethyl hydroxychromans levels in the liver and
      plasma. The CLA diet induced a significant increase in alpha-tocopherol transfer
      protein and mRNA levels in the liver. CLA resulted in a decrease in catalase and
      glutathione peroxidase activities and peroxisome proliferator alpha mRNA levels
      but had no effect on levels of mRNAs for other nuclear transcription factors in
      the liver. CONCLUSION: The increase in vitamin E status in CLA-fed mice is not
      due to altered absorption and metabolism of vitamin E but might be related to the
      induction of alpha-tocopherol transfer protein expression in the liver. The
      regulation of the activities of catalase and glutathione peroxidase by CLA is not
      mediated by vitamin E accumulation in the liver.

PMID- 21872435
TI  - Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and
      atherogenesis.
AB  - OBJECTIVE: To explain why vegetarian subjects develop morbidity and mortality
      from cardiovascular diseases unrelated to vitamin B status and Framingham
      criteria. METHODS: A study of 24 rural male subjects 18 to 30 y old and 15 urban
      male controls was conducted in the Sahel region of Chad. Food consumption was
      determined from a dietary questionnaire, and overall health status was assessed
      by body weight, body mass index, serum albumin, plasma transthyretin, urinary
      nitrogen, and creatinine. Plasma lipids, vitamins B6, B9 and B12, homocysteine,
      and related sulfur amino acids were measured as selected cardiovascular disease
      risk factors. RESULTS: Body weight, body mass index, blood, and urinary markers
      of protein status were significantly lower, with an estimated 10% decrease of
      lean body mass in the study group compared with urban controls. Neither lipid
      fractions nor plasma levels of vitamins B6, B9, and B12 were significantly
      different between the two groups. Although the mean consumption of sulfur amino
      acids (10.4 mg.kg(-1).d(-1)) by rural subjects was significantly below the
      recommended dietary allowances (13 mg.kg(-1).d(-1)), plasma methionine values
      were similar in the two groups. In contrast, homocysteine concentration was
      significantly increased (18.6 MUmol/L, P < 0.001), and the levels of cysteine and
      glutathione were significantly decreased in the study group, demonstrating
      inhibition of the trans-sulfuration pathway. The strong negative correlation (r =
      -0.71) between transthyretin and homocysteine implicated lean body mass as a
      critical determinant of hyperhomocysteinemia. CONCLUSION: The low dietary intake
      of protein and sulfur amino acids by a plant-eating population leads to
      subclinical protein malnutrition, explaining the origin of hyperhomocysteinemia
      and the increased vulnerability of these vegetarian subjects to cardiovascular
      diseases.

PMID- 21872436
TI  - Effects of soybean peptide on immune function, brain function, and neurochemistry
      in healthy volunteers.
AB  - OBJECTIVE: Soybeans, an excellent source of dietary peptides, have beneficial
      effects on health. We investigated the effect of the soybean peptide on immune
      function, brain function, and neurochemistry in healthy volunteers. METHODS: Near
      infrared spectroscopy (NIRS) was used to analyze brain cerebral blood flow. The A
      and DA levels in the serum were analyzed by ELISA kit. The total number of
      leukocytes was recorded with a standard counter. Flow cytometry was used to
      assess lymphocyte subset levels. RESULTS: Cell numbers were upregulated in the
      group that had fewer leukocytes but downregulated in the group with more
      leukocytes. For the lymphocyte-rich type, lymphocyte counts tended to decrease,
      accompanied by an increase in granulocyte numbers. For the granulocyte-rich type,
      granulocyte counts tended to increase, but lymphocyte counts also increased. The
      numbers of CD11b(+) cells and CD56(+) cells increased significantly. Soybean
      peptide decreased the adrenalin level in plasma but increased the level of
      dopamine. Near-infrared spectroscopy showed significant increases in the
      amplitudes of theta, alpha-2, and beta-L frequency bands after the ingestion of
      peptides. CONCLUSION: Soybean peptides can modulate cellular immune systems,
      regulate neurotransmitters, and boost brain function.

PMID- 21872437
TI  - Calorie and macronutrients intake in people with spinal cord injuries: an
      analysis by sex and injury-related variables.
AB  - OBJECTIVE: Current studies suggest that two of every three persons with spinal
      cord injury are at risk for the metabolic consequences of obesity. The objective
      of this study was to assess the dietary intakes in people with spinal cord injury
      based on sex- and injury-related variables. METHODS: In total 162 people with
      spinal cord injury participated in this cross-sectional study. Their dietary
      intakes were assessed by a semiquantitative food-frequency questionnaire.
      RESULTS: The percentages of total energy intake derived from macronutrients were
      53% carbohydrate, 10% protein, and 37% fat for men and 52% carbohydrate, 11%
      protein, and 39% fat for women. There was excessive consumption of simple
      carbohydrates (102.17 +/- 40.83). The participants with longer times since injury
      had lower cholesterol intakes (P = 0.02). The individuals with an incomplete
      injury consumed significantly more monounsaturated fatty acids (n = 114, 27.2 +/-
      12.01 g) than those with a complete injury (n = 48, 23.6 +/- 8.08 g, P = 0.03).
      There was a significant positive correlation of age and time since injury with
      fiber intake (P < 0.05). CONCLUSION: The balance of macronutrients shifted toward
      intakes of fat and simple carbohydrates at the expense of complex carbohydrates,
      fiber, and protein in these participants. Mean amounts of polyunsaturated and
      monounsaturated fatty acids in these participants were above the recommended
      intakes. Older participants and those with a longer time since injury tended to
      have lower calorie, fat, carbohydrate, saturated fat, and cholesterol intakes and
      higher fiber intakes.

PMID- 21872438
TI  - Modulation of cytokines, resistin, and distribution of adipose tissue in C57BL/6
      mice by different high-fat diets.
AB  - OBJECTIVE: To investigate whether changing the lipid source induces metabolic
      changes and/or modulates the adipose tissue distribution in mice fed with a high
      fat (HF) diet. METHODS: C57BL/6 mice were subjected to a 10-wk control diet (10%
      fat) or an HF diet (60% fat) containing lard (HF-L), olive oil (HF-O), sunflower
      oil, or canola oil. Food intake and body weight were measured. At euthanasia,
      blood was collected and adipose tissue was dissected. Serum hormones and
      cytokines were determined. RESULTS: The plasma insulin levels were higher in the
      HF-L and HF-O groups than in the other three groups (P < 0.0001). The levels of
      resistin were highest in the HF-L and HF-O groups (P < 0.0001). Leptin expression
      was also highest in these two groups (P < 0.0001). Of the four groups,
      interleukin-6 was expressed at the highest level in the HF-L group (P < 0.0005),
      whereas adiponectin was expressed at the lowest level (P < 0.0001). The
      accumulation of subcutaneous and visceral adipose tissues was higher in the HF-L
      group compared with the other groups. This group was hypertrophic because of
      excess subcutaneous fat and epididymal fat in the adipocytes. However, the ratio
      of subcutaneous to visceral fat was significantly lower in the HF-L and HF-O
      groups compared with the other groups. CONCLUSION: In mice fed fat-rich diets,
      the level of adipokines, the distribution of adipose tissue, and the metabolism
      of carbohydrates are more significantly influenced by the lipid content rather
      than the absolute amount of lipid.

PMID- 21872439
TI  - Recurrence of angina pectoris after percutaneous coronary intervention is reduced
      by statins in Japanese patients.
AB  - BACKGROUND: Statins have been reported to reduce cardiovascular events in
      patients with coronary artery disease (CAD). Percutaneous coronary intervention
      (PCI) is commonly used to relieve ischemic symptoms in patients with CAD.
      However, there is little information on the effect of statins on cardiovascular
      events after PCI, even in the era of coronary stent implantation. METHODS: A
      total of 1019 patients with acute or chronic CAD and modest total cholesterol
      levels (180-240 mg/dl) were enrolled and randomly assigned to treatment with or
      without statins. We evaluated the effect of any available statin on the incidence
      of cardiovascular events after PCI. The primary endpoint was a composite of
      cardiovascular death, nonfatal acute myocardial infarction (MI), recurrent angina
      pectoris requiring emergency rehospitalization (rAP), heart failure, and stroke.
      RESULTS: Indications for PCI were stable angina in 54%, ST-elevation MI in 41%
      and non-ST-elevation MI/unstable angina pectoris in 5%. After 2 years of statin
      treatment, low-density lipoprotein cholesterol (LDL-C) decreased from 133 to 96
      mg/dl. Stents were implanted in 84% of all cases. The primary endpoint event rate
      was 9.5% in the statin group and 14.7% in the non-statin group (p=0.0292). Of all
      primary endpoint events, only rAP was significantly suppressed by statins
      (p=0.0027). In rAP patients, coronary angiography revealed that statins
      suppressed restenosis but not new lesions. CONCLUSIONS: For Japanese CAD patients
      treated with PCI and stent implantation, statin therapy reduced the incidence of
      recurrent cardiovascular events, particularly rAP. Discretionary statin treatment
      to achieve LDL-C levels <100 mg/dl effectively reduced restenosis causing rAP.

PMID- 21872440
TI  - The effects of the ketogenic diet on behavior and cognition.
AB  - Multiple forms of the ketogenic diet (KD) have been successfully used to treat
      drug-resistant epilepsy, however its mainstream use as a first-line therapy is
      still limited. Further investigation into its clinical efficacy as well as the
      molecular basis of activity is likely to assist in the reversal of any resistance
      to its implementation. In this review we shall attempt to elucidate the current
      state of experimental and clinical data concerning the neuroprotective and
      cognitive effects of the KD in both humans and animals. Generally, it has been
      shown by many research groups that effective implementation of KD exerts strong
      neuroprotective effects with respect to social behavior and cognition. We will
      also elucidate the role of KD in the interesting relationship between sleep,
      epilepsy and memory. Currently available evidence also indicates that, under
      appropriate control, and with further studies investigating any potential long
      term side effects, the KD is also a relatively safe intervention, especially when
      compared to traditional anti-epileptic pharmacotherapeutics. In addition, due to
      its neuroprotective capacity, the KD may also hold potential benefit for the
      treatment of other neurological or neurodegenerative disorders.

PMID- 21872441
TI  - Neuroprotection in metabolism-based therapy.
AB  - Metabolism-based therapy has been used successfully in the treatment of seizures
      but study of its use in other neurodegenerative disorders is growing. Data
      demonstrating the use of different forms of metabolism-based therapy in human
      trials of Alzheimer disease and Parkinson disease are discussed. Animal and in
      vitro studies have shed light on metabolism-based therapy's mechanisms in these
      diseases, as well as ALS, aging, ischemia, trauma and mitochondrial cytopathies.
      Additional insights may be obtained by considering the role of metabolism-based
      therapy in cell disability and death (specifically apoptosis, excitotoxicity, and
      autophagy).

PMID- 21872442
TI  - Analysis of efficacy and side effects in CATIE demonstrates drug response
      subgroups and potential for personalized medicine.
AB  - OBJECTIVE: This study aims to improve understanding of antipsychotic non/response
      and assess the potential for personalized schizophrenia treatment. METHODS: We
      used data from the Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE). Efficacy measures included the Positive and Negative Syndrome Scale
      (PANSS) and neurocognitive functioning. Side effect measures included weight,
      lipids, glucose, heart rate and QT prolongation. Latent class analysis was
      conducted for each of the five drugs on the individual treatment effects to study
      whether there were subgroups of drug responders. The posterior probabilities of
      belonging to a particular response group were correlated across drugs to examine
      if patients not responding to one drug are likely to respond to a different drug
      and whether response to one drug may help to predict response to another drug.
      RESULTS: We identified four qualitatively distinct response groups: Optimal
      Responders, Average Responders, Global Responders and Non-Responders. Different
      patterns of correlations with demographics and clinical variables across classes
      provided further support for the validity of these groups. The low correlations
      between posterior probabilities of the same response groups across drugs implied
      that patients generally belonged to different response groups for different
      drugs. CONCLUSIONS: Our results demonstrate the existence of subgroups of
      patients characterized by distinct patterns of drug response. Further, findings
      suggest that patients who experience a poor response to one drug may be an
      optimal responder to another antipsychotic. Taken together these findings
      demonstrate the potential to personalize schizophrenia treatment and highlight
      the importance of identifying better predictors of drug response.

PMID- 21872443
TI  - Substance use and schizophrenia: adverse correlates in the CATIE study sample.
AB  - OBJECTIVE: This study examined the relationship between severity of illicit
      substance use at the time of study entry in a sample of patients diagnosed with
      schizophrenia and 18-month longitudinal outcomes, including psychopathology,
      depression, neurocognition, and quality of life. METHODS: Subjects in the
      Clinical Antipsychotic Trials of Intervention Effectiveness (N=1432) were divided
      into three groups according to baseline data: (1) those with moderate/severe drug
      use, (2) those with mild drug use, and (3) non-users of illicit substances. The
      groups were compared on other baseline characteristics. Mixed model analysis was
      used to compare outcomes between the groups using all available outcome data over
      18 months, controlling for potential confounding baseline characteristics. Least
      square means were compared between pairs of groups in the mixed models. RESULTS:
      Significantly poorer outcomes were observed in the domains of psychosis, symptoms
      of depression, and quality of life for moderate/severe drug users in comparison
      with both mild users and abstainers. No significant differences were found on
      neurocognitive functioning or days of employment. CONCLUSIONS: This study
      suggests that drug use-related impairment co-morbid with schizophrenia may not be
      a function of use per se but rather, of the severity of use. It highlights the
      importance of comprehensive assessment and treatment of illicit substance abuse
      in schizophrenia. Long-term treatment approaches that integrate harm reduction
      strategies may offer promise in maximizing positive outcomes for such dually
      diagnosed patients.

PMID- 21872445
TI  - Adjunct minocycline to clozapine treated patients with persistent schizophrenia
      symptoms.

PMID- 21872444
TI  - Proton magnetic resonance spectroscopy and thought disorder in childhood
      schizophrenia.
AB  - OBJECTIVE: Although magnetic resonance spectroscopy has identified metabolic
      abnormalities in adult and childhood schizophrenia, no prior studies have
      investigated the relationship between neurometabolites and thought disorder. This
      study examined this association in language-related brain regions using proton
      magnetic resonance spectroscopic imaging ((1)H MRSI). METHOD: MRSI was acquired
      bilaterally from 28 youth with childhood-onset schizophrenia and 34 healthy
      control subjects in inferior frontal, middle frontal, and superior temporal gyri
      at 1.5T and short echo time (TR/TE = 1500/30 ms). CSF-corrected "total NAA"
      (tNAA; N-acetyl-aspartate + N-acetyl-aspartyl-glutamate), glutamate + glutamine
      (Glx), creatine + phosphocreatine (Cr + PCr), choline compounds (Cho), and myo
      inositol (mI) were assayed in manually drawn regions-of-interest partitioned into
      gray matter, white matter, and CSF and then coregistered with MRSI. Speech
      samples of all subjects were coded for thought disorder. RESULTS: In the
      schizophrenia group, the severity of formal thought disorder correlated
      significantly with tNAA in the left inferior frontal and superior temporal gyri
      and with Cr + PCr in left superior temporal gyrus. CONCLUSIONS: Neurometabolite
      concentrations in language-related brain regions are associated with thought
      disorder in childhood-onset schizophrenia.

PMID- 21872446
TI  - Epidermal growth factor-induced matrix metalloproteinase-1 expression is
      negatively regulated by p38 MAPK in human skin fibroblasts.
AB  - BACKGROUND: Many extracellular stimuli, including epidermal growth factor (EGF),
      are known to induce MMP-1 expression. Recently, several reports have shown that
      ERK activity plays an important role in EGF-induced MMP-1 expression. However,
      EGF is also known to activate many signaling pathways in addition to the ERK
      pathway, but the roles of these pathways during the induction of MMP-1 by EGF are
      unclear. OBJECTIVE: We investigated the role of JNK, p38 MAPK, and PI3K/Akt
      pathways in EGF-induced MMP-1 expression in human skin fibroblasts. Then, we
      further explored the inhibitory effect of p38 MAPK pathway on EGF-induced MMP-1
      expression and studied the molecular mechanisms involved in the processes.
      METHODS: Human skin fibroblasts were pretreated with various chemical inhibitors
      or small interfering RNA (siRNA) at the indicated concentrations and then treated
      with EGF, TNF-alpha, or IL-1beta for the indicated times. Protein and mRNA levels
      of various target molecules were assessed by Western blotting and quantitative
      real-time PCR, respectively. RESULTS: We found that EGF-induced MMP-1 expression
      was positively regulated by JNK as well as ERK but negatively regulated by p38
      MAPK in human skin fibroblasts. On the other hand, the PI3K/Akt pathway did not
      significantly affect MMP-1 induction by EGF. Then we found that the inhibition of
      p38 MAPK pathway specifically increased the MMP-1 expression stimulated by EGF
      but not by TNF-alpha or IL-1beta, indicating that the effect of p38 MAPK on MMP-1
      expression may be stimulus-type specific in human skin fibroblasts. In addition,
      the inhibitory effect of p38 MAPK on EGF-induced MMP-1 expression was shown to be
      mainly mediated by p38-alpha MAPK. Our further studies showed that the inhibition
      of p38 MAPK but not PI3K specifically increased EGF-induced ERK and JNK
      activations, and that the augmentation of EGF-induced MMP-1 expression by p38
      MAPK inhibition was significantly attenuated by inhibiting the activities of ERK
      and/or JNK. CONCLUSIONS: Our results indicate that EGF-induced MMP-1 expression
      is differentially regulated by the JNK, p38 MAPK, and PI3K/Akt pathways, and
      suggest that p38 MAPK negatively regulates EGF-induced MMP-1 expression by
      suppressing the activations of ERK and JNK.

PMID- 21872447
TI  - Human catestatin enhances migration and proliferation of normal human epidermal
      keratinocytes.
AB  - BACKGROUND: Skin-derived antimicrobial peptides, such as human beta-defensins and
      cathelicidins, actively contribute to host defense by inactivating
      microorganisms. Catestatin, a neuroendocrine peptide that affects human autonomic
      functions, has recently been detected in keratinocytes upon injury/infection
      where it inhibits the growth of pathogens. Human catestatin exhibits three single
      nucleotide polymorphisms: Gly364Ser, Pro370Leu, and Arg374Gln. OBJECTIVE: To
      investigate the effects of human catestatin and its variants on keratinocyte
      migration and proliferation, and to elucidate the possible signaling mechanisms
      involved. METHODS: The migration of normal human keratinocytes was analyzed using
      Boyden microchamber assay and in vitro wound closure assay. Cell proliferation
      was evaluated by BrdU incorporation, cell count assay and cell cycle analysis.
      Intracellular Ca(2+) mobilization was measured using a fluorescent calcium assay
      kit. The phosphorylation of epidermal growth factor receptor (EGFR), Akt, and
      MAPKs was determined by Western blotting. RESULTS: Catestatin and its variants
      dose-dependently enhanced keratinocyte migration and proliferation. Moreover,
      catestatin peptides increased intracellular Ca(2+) mobilization and induced the
      phosphorylation of EGFR, Akt, extracellular signal-regulated kinase (ERK), and
      p38 in keratinocytes. The induction of keratinocyte migration and proliferation
      by catestatin peptides involved G-proteins, phospholipase C, EGFR, PI3-kinase,
      ERK, and p38, as evidenced by the specific inhibitory effects of pertussis toxin
      (G-protein inhibitor), U-73122 (phospholipase C inhibitor), AG1478 (EGFR
      inhibitor), anti-EGFR antibody, wortmannin (PI3-kinase inhibitor), U0126 (ERK
      inhibitor), and SB203580 (p38 inhibitor), respectively. CONCLUSION: Besides
      inhibiting the growth of skin pathogens, catestatin peptides may also contribute
      to cutaneous wound closure by enhancing keratinocyte migration and proliferation
      at the wound site.

PMID- 21872448
TI  - Erythrodermic cutaneous T-cell lymphoma: how to differentiate this rare disease
      from atopic dermatitis.
AB  - Sezary syndrome and erythrodermic mycosis fungoides have been recognized as part
      of a broader spectrum of erythrodermic cutaneous T-cell lymphoma (E-CTCL). Atopic
      dermatitis (AD) is the most common, chronic inflammatory skin disease and can, in
      its most severe form, manifest as erythroderma. It is often difficult to
      clinically distinguish E-CTCL from various common and benign diseases presenting
      as erythroderma, including AD. Differentiating E-CTCL from benign inflammatory
      diseases is important to ensure proper disease management, and to provide
      accurate prognostic information. Clinical and laboratory features, including
      pruritus and serum levels of soluble interleukin-2 receptor, lactate
      dehydrogenase (LDH), immunoglobulin E (IgE), and several chemokines, do not
      differentiate E-CTCL from AD. In contrast, low serum allergen-specific IgE
      levels, presence of Sezary cells in peripheral blood, histological findings, and
      high CD4/CD8 ratio and CCR10 positivity in lesional skin are helpful in reaching
      a correct diagnosis. Patients with E-CTCL have been treated with oral etretinate,
      intravenous or subcutaneous interferon, bexarotene, extracorporeal photopheresis,
      total body surface electron beam, chemotherapy, or any combination of these
      modalities. Older patients, high serum LDH levels, and high number of circulating
      atypical lymphocytes are associated with poor prognosis.

PMID- 21872449
TI  - In vitro activity of polymyxins in combination with beta-lactams against clinical
      strains of Pseudomonas aeruginosa.
AB  - The emergence of multidrug-resistant (MDR) strains has made it difficult to treat
      infections caused by Pseudomonas aeruginosa. In order to develop new alternative
      therapies for the treatment of MDR P. aeruginosa infections, the antimicrobial
      activities of different antibiotic combinations have been studied in vitro and in
      vivo. In this study, the in vitro antimicrobial activities of six different
      combinations of polymyxins and beta-lactams against 34 clinical isolates of P.
      aeruginosa were evaluated. For the combinations tested by the checkerboard
      method, an indifferent effect was observed for all strains. However, 27 strains
      (19 MDR) showed reductions in their minimal inhibitory concentration (MIC) for at
      least one of the antibiotics in the combinations evaluated. Combination with
      polymyxins resulted in reductions of the beta-lactam MICs, with a change in the
      resistance category to susceptible in eight MDR strains. These results from the
      in vitro evaluation suggest that combinations of polymyxins and beta-lactams may
      significantly reduce the MICs of the antibiotics tested. These combinations
      require further evaluation for use in medical practice.

PMID- 21872450
TI  - Vancomycin susceptibility of meticillin-resistant Staphylococcus aureus (MRSA)
      bacteraemia isolates in an Italian hospital.

PMID- 21872451
TI  - Impaired neural processing of social attribution in anorexia nervosa.
AB  - Anorexia nervosa (AN) patients have been found to have problems in social
      cognition, including the process of thinking about other people's thoughts and
      feelings, often referred to as Theory of Mind (ToM). We examined neural
      correlates relating to thinking about social relationships in 17 women in
      recovery from anorexia (RAN) and 17 healthy women (CON) using a functional
      magnetic resonance imaging (fMRI) task. The task consisted of short videos of
      moving shapes that subjects viewed either in the context of performing a social
      decision related to how the shapes interacted: "People: All friends?" or in the
      context of performing a visuospatial task related to how the shapes moved after
      bumping into each other: "Bumper cars: Same weight?". The RAN participants showed
      reduced activation in the social cognition network, with the most robust
      differences in the right temporoparietal junction (RTPJ). There were no
      significant differences between the CON and RAN groups in regions more active
      during the visuospatial task. These neural correlates show differences in the
      processing of social knowledge in RAN subjects suggesting that biological
      impairments in social cognition may contribute to pathology in AN.

PMID- 21872452
TI  - Neural correlates of sleepiness induced by catecholamine depletion.
AB  - Although extensive indirect evidence exists to suggest that the central
      dopaminergic system plays a significant role in the modulation of arousal, the
      functional effect of the dopaminergic influence on the regulation of the sleep
      wake cycle remains unclear. Thirteen healthy volunteers and 15 unmedicated
      subjects with a history of major depressive disorder underwent catecholamine
      depletion (CD) using oral alpha-methyl-para-tyrosine in a randomized, placebo
      controlled, double-blind, crossover study. The main outcome measures in both
      sessions were sleepiness (Stanford-Sleepiness-Scale), cerebral glucose metabolism
      (positron emission tomography), and serum prolactin concentration. CD
      consistently induced clinically relevant sleepiness in both groups. The CD
      induced prolactin increase significantly correlated with CD-induced sleepiness
      but not with CD-induced mood and anxiety symptoms. CD-induced sleepiness
      correlated with CD-induced increases in metabolism in the medial and orbital
      frontal cortex, bilateral superior temporal cortex, left insula, cingulate motor
      area and in the vicinity of the periaqueductal gray. This study suggests that the
      association between dopamine depletion and sleepiness is independent of the brain
      reward system and the risk for depression. The visceromotor system, the cingulate
      motor area, the periaqueductal gray and the caudal hypothalamus may mediate the
      impact of the dopaminergic system on regulation of wakefulness and sleep.

PMID- 21872453
TI  - Biosorption kinetics, thermodynamics and isosteric heat of sorption of Cu(II)
      onto Tamarindus indica seed powder.
AB  - Biosorption of Cu(II) by Tamarindus indica seed powder (TSP) was investigated as
      a function of temperature in a batch system. The Cu(II) biosorption potential of
      TSP increased with increasing temperature. The rate of the biosorption process
      followed pseudo second-order kinetics while the sorption equilibrium data well
      fitted to the Langmuir and Freundlich isotherm models. The maximum monolayer
      Cu(II) biosorption capacity increased from 82.97 mg g(-1) at 303 K to 133.24 mg
      g(-1) at 333 K. Thermodynamic study showed spontaneous and endothermic nature of
      the sorption process. Isosteric heat of sorption, determined using the Clausius
      Clapeyron equation increased with increase in surface loading showing its strong
      dependence on surface coverage. The biosorbent was characterized by scanning
      electron microscopy (SEM), surface area and porosity analyzer, X-ray diffraction
      (XRD) spectrum and Fourier transform infrared (FTIR) spectroscopy. The results of
      FTIR analysis of unloaded and Cu(II)-loaded TSP revealed that -NH(2), -OH, -C=O
      and C-O functional groups on the biosorbent surface were involved in the
      biosorption process. The present study suggests that TSP can be used as a
      potential, alternative, low-cost biosorbent for removal of Cu(II) ions from
      aqueous media.

PMID- 21872454
TI  - A tumor pH-responsive complex: carboxyl-modified hyperbranched polyether and cis
      dichlorodiammineplatinum(II).
AB  - To realize the pH-targeting delivery of antitumor drug cis
      dichlorodiammineplatinum(II) (cisplatin, CDDP), a tumor pH-responsive polymer
      platinum(II) complex (Suc-HPMHO-CDDP) from carboxyl-modified hyperbranched
      polyether (Suc-HPMHO) and cisplatin was designed and prepared. Because of the
      existence of hydrophobic core and ionization of surface carboxylic acid, Suc
      HPMHO showed reversible pH-response in aqueous solution, and its responding pH
      value could be readily adjusted by only changing the degree of carboxylation of
      Suc-HPMHO. With plenty of terminal carboxyl groups, Suc-HPMHO could form the
      complex with CDDP by substituting the chloride ions with carboxyls. Methyl
      tetrazolium (MTT) assay showed that Suc-HPMHO had low cytotoxicity, while Suc
      HPMHO-CDDP complex presented a similar antitumor effect with the free CDDP. Under
      the tumor acidic pH (pH(e)), Suc-HPMHO-CDDP complex deposited around/in cells
      because of its pH-response. Therefore, the pH-targeting of Suc-HPMHO-CDDP complex
      to tumor tissue could be realized. All of these results show that the tumor pH
      responsive Suc-HPMHO-CDDP complex is a potential pH-targeting drug delivery
      system in cancer therapy.

PMID- 21872455
TI  - Interpenetrating polymer network (IPN) scaffolds of sodium hyaluronate and sodium
      alginate for chondrocyte culture.
AB  - In this study, porous sodium hyaluronic acid/sodium alginate (HA/SA) scaffold
      based on interpenetrating polymeric network (IPN) technique has been fabricated,
      where HA and SA were cross-linked with poly(ethylene glycol) diglycidyl ether
      (PEGDG) and calcium chloride, respectively. The mean pore size and the swelling
      ratio of fabricated scaffolds decreased, and the compressive strength increased
      as the content of SA increased in HA/SA IPN scaffold. Rabbit chondrocytes were
      seeded within the HA/SA IPN scaffolds, and then their proliferation as well as
      chondrogenic differentiation was examined. DNA contents observed from the
      chondrocytes cultured in the IPN scaffolds increased with time over 21 days,
      which demonstrated that the rabbit chondrocytes continued to proliferate in HA/SA
      scaffolds. Results of the 1,9-dimethylmethylene blue (DMMB) and p
      dimethylaminobenzaldehyde (DMBA) assays showed that glycosaminoglycan (s-GAG) and
      collagen contents increased over culture period, indicating the chondrogenic
      differentiation in the scaffold. Reverse transcription-polymerase chain reaction
      (RT-PCR) results showed the expression of type II collagen, the main chondrogenic
      differentiation marker. The bands indicating mRNA expression of type II collagen
      increased with the culture period. These results demonstrated that the porous
      HA/SA IPN scaffolds were successfully prepared and could serve as an effective
      delivery system of the three-dimensional culture of chondrocytes.

PMID- 21872456
TI  - Microscopic evidence for inclusion of Parvamoeba Rogerson, 1993 into the order
      Himatismenida (Amoebozoa).
AB  - I have re-investigated the light-microscopic features of Parvamoeba rugata
      Rogerson, 1993, type strain CCAP 1556/1. The major characters of amoebae
      correspond to the initial description of this species. However, one peculiarity
      demonstrated by the cells during adhesion to the substratum, seems to have been
      partly underestimated previously. At the same time it is crucial for the
      explanation of this species' position in the molecular phylogenetic trees and the
      recent system of Amoebozoa. This feature is the formation of a thin sheet of
      hyaloplasm on the ventral side of the cell that is used for adhesion to the
      substratum and locomotion, shared between Parvamoeba and members of the order
      Himatismenida. This explains the position of Parvamoeba as a sister clade to
      Cochliopodiidae in the molecular phylogenetic trees and justifies the recent
      inclusion of this genus into the order Himatismenida. In addition I sequenced the
      small-subunit ribosomal RNA of P. rugata and demonstrated that it was 99.5-99.7%
      similar to that of P. monoura Cole et al., 2010. This raises a question of the
      possible identity of these two species, however, several persistent morphological
      differences do not permit the unification of them, at least until more genes
      demonstrate identical sequences between these species.

PMID- 21872457
TI  - Alpha-1 antitrypsin is elevated in exhaled breath condensate and serum in
      exacerbated COPD patients.
AB  - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD)
      significantly contribute to COPD-related morbidity. Diagnosis of COPD
      exacerbations may be improved by analyzing biomarkers such as alpha-1 antitrypsin
      (AAT). AAT is an acute-phase protein and inhibitor of neutrophil elastase.
      Deficiency of AAT may result in early-onset respiratory symptoms. Measurement of
      exhaled breath condensate (EBC) is a noninvasive method to investigate biomarkers
      present in the epithelial lining fluid, such as AAT. OBJECTIVE: To investigate
      whether AAT can be detected and quantified in EBC and to compare AAT levels in
      the EBC of healthy controls, patients with COPD, and during exacerbations of
      COPD. METHODS: EBC from 10 healthy controls, 17 subjects with COPD, and 18
      subjects with exacerbations of COPD was collected with the RTubeTM device. AAT
      from EBC and serum were quantified by ELISA. RESULTS: AAT in EBC was detectable
      in every individual. Patients with exacerbations of COPD had significantly
      increased AAT values (mean, 514.33 pg/mL, [SD 279.41 ]) compared with healthy
      controls (mean, 251.32 pg/mL, [SD 44.71]) and stable COPD patients (mean, 242.01
      pg/mL [SD 65.74]) (P=0.0003; P=0.00003). EBC AAT showed only a correlation trend
      with serum AAT (r=0.3, P=0.054). CONCLUSIONS: AAT in EBC was detectable and
      quantifiable. AAT measured in EBC was significantly increased during
      exacerbations of COPD and can potentially be used as a biomarker in
      exacerbations.

PMID- 21872458
TI  - NADPH oxidase p22phox polymorphisms and oxidative stress in patients with
      obstructive sleep apnoea.
AB  - BACKGROUND: Obstructive Sleep Apnoea (OSA) is associated with increased oxidative
      stress. NADPH oxidases are the main source of Reactive Oxygen Species (ROS) in
      the vasculature. Several polymorphisms related to NADPH oxidase expression or
      activity have been identified. We compared the distribution of the allelic
      frequencies of A-930G and C242T polymorphisms and their possible relationship
      with the levels of 8-isoprostanes as a marker of oxidative stress in patients
      with OSA and in a control group without OSA. METHODS: This is a case-control
      study. We determined the A-930G and C242T p22phox genotypes in 427 patients with
      OSA and in 139 healthy subjects recruited from the Sleep Unit of Son Dureta
      University Hospital, (Palma de Mallorca, Spain). 8-Isoprostane was measured as an
      oxidative stress marker. RESULTS: The distribution of the p22phox genotypes in
      OSA and in control subjects was different. The risk of OSA was associated with
      the presence of the G allele in the A-930G p22phox independently of age, gender,
      Body Mass Index (BMI), hypertension, dyslipemia and diabetes, but no association
      was found with the C242T polymorphism. The median level of 8-isoprostane was
      significantly higher in OSA patients. Synergic effect in 8-Isoprostane levels was
      observed when these two polymorphisms were analysed together. CONCLUSION: the A
      930G polymorphism of the p22phox gene may play an important role in genetic
      susceptibility to OSA. Furthermore, the C242T and A-930G polymorphisms of the
      p22phox gene have a synergic effect on the 8-isoprostane levels, suggesting that
      they may be involved in the development of oxidative stress in these patients.

PMID- 21872459
TI  - Label-free optical bifunctional oligonucleotide probe for homogeneous
      amplification detection of disease markers.
AB  - Oligonucleotide-based detection schemes that avoid chemical modification possess
      significant advantages, including simplified design, intrinsic affinity for
      targets, low cost and ease to extend applications. In this contribution, we
      developed a label-free self-locked bifunctional oligonucleotide probe (signaling
      probe) for the detection of different disease markers in parallel. Two signal
      enhancement techniques based on isothermal circular strand-displacement
      polymerization reaction, cyclical nucleic acid strand-displacement polymerization
      (CNDP) and cyclical common (nonnucleic acid) target-displacement polymerization
      (CCDP), were employed to implement the amplification assay for p53 gene and PDGF
      BB, respectively. The attractive assay properties confirmed the effectiveness of
      isothermal polymerization in common biosensing systems without evolving any
      chemical modification: PDGF could be detected down to 0.87ng/mL, and a dynamic
      response range of 8-5000ng/mL was achieved; The capability to screen the p53 gene
      was also considerably improved, including the detection limit, sensitivity,
      dynamic range and so on. Moreover, because no any chemical modification of the
      signaling probe was acquired and different targets were separately detected in
      homogeneous solution. This interrogating platform exhibits the design
      flexibility, convenience, simplicity and cost-effectiveness. The success achieved
      here is expected to serve as a significant step toward the development of robust
      label-free oligonucleotide probes in biomarker profiling and disease diagnostics.

PMID- 21872460
TI  - Multienzyme-nanoparticles amplification for sensitive virus genotyping in
      microfluidic microbeads array using Au nanoparticle probes and quantum dots as
      labels.
AB  - A novel microfluidic device with microbeads array was developed and sensitive
      genotyping of human papillomavirus was demonstrated using a multiple-enzyme
      labeled oligonucleotide-Au nanoparticle bioconjugate as the detection tool. This
      method utilizes microbeads as sensing platform that was functionalized with the
      capture probes and modified electron rich proteins, and uses the horseradish
      peroxidase (HRP)-functionalized gold nanoparticles as label with a secondary DNA
      probe. The functionalized microbeads were independently introduced into the
      arrayed chambers using the loading chip slab. A single channel was used to
      generate weir structures to confine the microbeads and make the beads array
      accessible by microfluidics. Through "sandwich" hybridization, the enzyme
      functionalized Au nanoparticles labels were brought close to the surface of
      microbeads. The oxidation of biotin-tyramine by hydrogen peroxide resulted in the
      deposition of multiple biotin moieties onto the surface of beads. This deposition
      is markedly increased in the presence of immobilized electron rich proteins.
      Streptavidin-labeled quantum dots were then allowed to bind to the deposited
      biotin moieties and displayed the signal. Enhanced detection sensitivity was
      achieved where the large surface area of Au nanoparticle carriers increased the
      amount HRP bound per sandwiched hybridization. The on-chip genotyping method
      could discriminate as low as 1fmol/L (10zmol/chip, SNR>3) synthesized HPV
      oligonucleotides DNA. The chip-based signal enhancement of the amplified assay
      resulted in 1000 times higher sensitivity than that of off-chip test. In
      addition, this on-chip format could discriminate and genotype 10copies/MUL HPV
      genomic DNA using the PCR products. These results demonstrated that this on-chip
      approach can achieve highly sensitive detection and genotyping of target DNA and
      can be further developed for detection of disease-related biomolecules at the
      lowest level at their earliest incidence.

PMID- 21872461
TI  - Piezoelectric immunosensor for direct and rapid detection of staphylococcal
      enterotoxin A (SEA) at the ng level.
AB  - A direct, label-free immunosensor was designed for the rapid detection and
      quantification of staphylococcal enterotoxin A (SEA) in buffered solutions using
      quartz crystal microbalance with dissipation (QCM-D) as transduction method. The
      sensing layer including the anti-SEA antibody was constructed by chemisorption of
      a self-assembled monolayer of cysteamine on the gold electrodes placed over the
      quartz crystal sensor followed by activation of the surface amino groups with the
      rigid homobifunctional cross-linker 1,4-phenylene diisothiocyanate (PDITC) and
      covalent linking of binding protein (protein A or protein G). Four anti-SEA
      antibodies (two of which from commercial source) have been selected to set up the
      most sensitive detection device. With the optimized sensing layer, a standard
      curve for the direct assay of SEA was established from QCM-D responses within a
      working range of 50-1000 or 2000 ngml(-1) with a detection limit of 20 ngml(-1).
      The total time for analysis was 15 min. Using a sandwich type assay, the response
      was ca. twice higher and consequently the lowest measurable concentration dropped
      down to 7 ngml(-1) for a total assay time of 25 min.

PMID- 21872462
TI  - Molecularly imprinted hydroxyapatite thin film for bilirubin recognition.
AB  - A novel piezoelectric sensor has been developed for bilirubin (BR) detection,
      based on the modification of molecularly imprinted hydroxyapatite (HAP) film onto
      a quartz crystal by molecular imprinting and surface sol-gel technique. The
      performance of the developed BR biosensor was evaluated and the results indicated
      that a sensitive BR biosensor could be fabricated. The obtained BR biosensor
      presents high-selectivity monitoring of BR, better reproducibility, shorter
      response time (37 min), wider linear range (0.05-80MUM) and lower detection limit
      (0.01MUM). The analytical application of the BR biosensor confirms the
      feasibility of BR detection in serum sample.

PMID- 21872463
TI  - Colorimetric and luminescent bifunctional Ru(II) complex-modified gold nano probe
      for sensing of DNA.
AB  - A colorimetric and luminescent bifunctional Ru(II) complex-modified gold nano
      probe for sensing ctDNA was developed. A new water-soluble Ru(II) complex
      containing an aromatic alpha-diimine ligand with an extended pi system was found
      to be emissive at about 588nm in water and the emission intensity of the complex
      was enhanced about 3.4-fold upon addition of calf thymus DNA (ctDNA) in aqueous
      buffer with no color changes. The detection limit was 70nM with a 1.2% relative
      standard deviation (RSD, n=5). The Ru(II) complex chromophore was used to modify
      8nm MHA carboxylate-functionalized gold nanoparticles to produce a colorimetric
      and luminescent bifunctional probe for sensing ctDNA in aqueous buffer at room
      temperature. The obvious change in visible color and enhancement of emission
      intensity of the functionalized gold-Ru(II) complex colloids upon addition of
      ctDNA was due to the electron or energy transfer between Ru(II) chromophore and
      the Au-NPs. The limit of detection was 1.0nM for ctDNA with a 4.5% RSD (n=5).
      With such a high sensitivity, the bifunctional Ru(II) complex-modified gold nano
      probe will be potentially suitable for the DNA sensing in bioanalytical
      application.

PMID- 21872464
TI  - Reduction of electrode polarization capacitance in low-frequency impedance
      spectroscopy by using mesh electrodes.
AB  - Dielectric measurements of biological samples are obscured by electrode
      polarization, which at low frequencies dominates over the actual sample response.
      Reduction of this artifact is especially necessary in studying interactions of
      electric field with biological systems in the alpha-dispersion range. We
      developed a method to reduce the influence of electrode polarization by employing
      mesh instead of solid electrodes as sensing probes, thereby reducing the area of
      the double layer. The design decreases the electrode-electrolyte contact area by
      almost 40% while keeping the bulk sample capacitance the same. Interrogation
      electric fields away from the electrode surface and sensitivity are unaffected.
      Electrodes were microfabricated (600MUm*50MUm, spacing of 100MUm) with and
      without mesh holes 7.5MUm*7.5MUm in size. Simulations of electric field performed
      using Comsol Multiphysics showed non-uniformity of the electric field within less
      than 1.5MUm from the electrode surface, which encompasses the double layer
      region, but at greater distance the solid and mesh electrodes gave the same
      results. Mesh electrodes reduced capacitance measurements for water and KCl
      solutions of different concentrations at low frequencies (<10kHz), while higher
      frequency capacitance remained the same for both electrode types, confirming our
      hypothesis that this design leaves the electric field mainly unaffected.
      Impedance measurements at low frequencies for water and mice heart mitochondrial
      suspension were lower for mesh than for solid electrodes. Comsol simulations
      confirmed these results by showing that mesh electrodes have a greater charge
      density than solid electrodes, which affects conductance. These electrodes are
      being used for mitochondrial membrane potential studies.

PMID- 21872465
TI  - Coordinated methyl-lysine erasure: structural and functional linkage of a Jumonji
      demethylase domain and a reader domain.
AB  - Both components of chromatin (DNA and histones) are subjected to dynamic
      postsynthetic covalent modifications. Dynamic histone lysine methylation involves
      the activities of modifying enzymes (writers), enzymes removing modifications
      (erasers), and readers of the epigenetic code. Known histone lysine demethylases
      include flavin-dependent monoamine oxidase lysine-specific demethylase 1 and
      alpha-ketoglutarate-Fe(II)-dependent dioxygenases containing Jumonji domains.
      Importantly, the Jumonji domain often associates with at least one additional
      recognizable domain (reader) within the same polypeptide that detects the
      methylation status of histones and/or DNA. Here, we summarize recent developments
      in characterizing structural and functional properties of various histone lysine
      demethylases, with emphasis on a mechanism of crosstalk between a Jumonji domain
      and its associated reader module(s). We further discuss the role of recently
      identified Tet1 enzyme in oxidizing 5-methylcytosine to 5-hydroxymethylcytosine
      in DNA.

PMID- 21872466
TI  - Structure, mechanism, and inhibition of histone deacetylases and related
      metalloenzymes.
AB  - Metal-dependent histone deacetylases (HDACs) catalyze the hydrolysis of acetyl-L
      lysine side chains in histone and nonhistone proteins to yield l-lysine and
      acetate. This chemistry plays a critical role in the regulation of numerous
      biological processes. Aberrant HDAC activity is implicated in various diseases,
      and HDACs are validated targets for drug design. Two HDAC inhibitors are
      currently approved for cancer chemotherapy, and other inhibitors are in clinical
      trials. To date, X-ray crystal structures are available for four human HDACs (2,
      4, 7, and 8) and three HDAC-related deacetylases from bacteria (histone
      deacetylase-like protein (HDLP); histone deacetylase-like amidohydrolase (HDAH);
      acetylpolyamine amidohydrolase (APAH)). Structural comparisons among these
      enzymes reveal a conserved constellation of active site residues, suggesting a
      common mechanism for the metal-dependent hydrolysis of acetylated substrates.
      Structural analyses of HDACs and HDAC-related deacetylases guide the design of
      tight-binding inhibitors, and future prospects for developing isozyme-specific
      inhibitors are quite promising.

PMID- 21872467
TI  - Prophylactic total gastrectomy for hereditary diffuse gastric cancer. Review of
      the literature.
AB  - Hereditary diffuse gastric cancer (HDGC) is characterized as an autosomal
      dominant cancer susceptibility syndrome largely attributable to germline
      mutations and deletions in the gene encoding E-cadherin, CDH1. Mutation carriers
      have a more than 70% lifetime risk of developing DGC and an elevated probability
      of lobular breast cancer. The aim of this review was to evaluate the results of
      surgical treatment for HDGC with special reference to the extent of its
      histological spread and to analyze the recent literature in order to provide an
      update on the current concepts of prophylactic gastrectomy for disease
      prevention. Nevertheless, it is not clear that our current knowledge of molecular
      and genetic diagnostics calls for the addition of HDGC to the roster of malignant
      familial syndromes in which early counseling and preventive surgical intervention
      should become the standard of care. Endoscopic screening cannot be recommended
      because the stomach appears normal and biopsies often fail to demonstrate signet
      ring cell adenocarcinoma. Prophylactic gastrectomy has provided many members of
      affected families with relief from GC with minimal implications.

PMID- 21872468
TI  - Effect of hot water extraction and liquid hot water pretreatment on the fungal
      degradation of biomass feedstocks.
AB  - Exhaustive hot water extraction (HWE) and liquid hot water (LHW) pretreatment
      were evaluated for their effects on degradation of biomass feedstocks (i.e., corn
      stover, wheat straw, and soybean straw) by Ceriporiopsis subvermispora. HWE (85 
      degrees C for 10 min) partially removed water soluble extractives and
      subsequently improved fungal degradation on wheat straw while it had little or no
      effect on the fungal degradation of corn stover and soybean straw. In contrast,
      LHW pretreatment at 170  degrees C for 3 min improved the fungal degradation of
      soybean straw; thus, lignin removal of 36.70% and glucose yield of 64.25% were
      obtained from the combined LHW and fungal pretreatment. However, corn stover,
      which was effectively degraded by fungal pretreatment alone, was less affected by
      this combined pretreatment. Our results indicated that a HWE or LHW pretreatment
      conducted under mild conditions worked synergistically with fungal degradation
      for some recalcitrant feedstocks.

PMID- 21872469
TI  - Direct prediction of bioethanol yield in sugar beet pulp using near infrared
      spectroscopy.
AB  - Sugar beets are a raw material for the production of sugar and ethanol. The
      decision on which end product to pursue could be facilitated by fast and reliable
      means of predicting the potential ethanol yield from the beets. A Near Infrared
      (NIR) Spectroscopy-based approach was tested for the direct prediction of the
      potential bioethanol production from sugar beets. A modified partial least
      squares (MPLS) regression model was applied to 125 samples, ranging from 21.9 to
      31.0 gL(-1) of bioethanol in sugar beet brei. The samples were analyzed in
      reflectance mode in a Direct Contact Food Analyser (DCFA) FOSS-NIRSystems 6500
      monochromator, with standard error of cross validation (SECV), standard error of
      prediction (SEP), coefficient of determination (r(2)) and coefficient of
      variation (CV) of 0.51, 0.49, 0.91 and 1.9 gL(-1), respectively. The NIR
      technique allowed direct prediction of the ethanol yield from sugar beet brei
      (i.e. the product obtained after sawing beets with a proper machine) in less than
      3 min.

PMID- 21872470
TI  - Evaluating and modeling biogas production from municipal fat, oil, and grease and
      synthetic kitchen waste in anaerobic co-digestions.
AB  - The feasibility of using synthetic kitchen waste (KW) and fat, oil, and grease
      (FOG) as co-substrates in the anaerobic digestion of waste activated sludge (WAS)
      was investigated using two series of biochemical methane potential (BMP) tests.
      Ranges of ideal substrate to inoculum (S/I) ratio were determined for the FOG
      (0.25-0.75) and KW (0.80-1.26) as single substrates in the first experiment. The
      second experiment, which estimated the methane production performances of FOG and
      KW as co-substrates for WAS co-digestion, was conducted based on the optimal
      parameters selected from the results of the first experiment. Results indicated
      that co-digestions with FOG and KW enhanced methane production from 117+/-2.02
      mL/gTVS (with only WAS) to 418+/-13.7 mL/gTVS and 324+/-4.11 mL/gTVS,
      respectively. FOG exhibited more biogas production than KW as co-substrate. Non
      linear regression results showed that co-substrate addition shortened the lag
      phases of organic biodegradation from 81.8 (with only WAS) to 28.3 h with FOG and
      3.90 h with KW.

PMID- 21872471
TI  - Acetylcholine receptor antibodies in patients with genetic myopathies: clinical
      and biological significance.
AB  - We report two patients with facioscapulohumeral muscular dystrophy (FSHD)
      presenting with atypical clinical features. Both were found to have antibodies to
      acetylcholine receptor (AChR-abs) and improved with immunosuppression. AChR-abs
      have also been reported in patients with other genetic myopathies and it is
      unlikely that the association is coincidental. There is increasing evidence that
      muscle fibre degeneration can cause innate immune responses (autoinflammation)
      that may lead to the breaking of immune tolerance and the generation of
      autoantibodies to muscle proteins. We compare and contrast this process with the
      pathogenesis of archetypical myasthenia gravis.

PMID- 21872472
TI  - ICU nurses' perceptions of responsibilities and organisation in relation to organ
      donation--a phenomenographic study.
AB  - OBJECTIVES: According to the Istanbul declaration, health services should create
      better routines for identifying potential donors. A previous study involving 702
      intensive and critical care (ICU) nurses revealed that only 48% trusted clinical
      diagnosis of brain death without a confirmatory cerebral angiography. The aim was
      to study ICU nurses' perceptions of their experiences of professional
      responsibilities and organisational aspects in relation to organ donation and how
      they understand and perceive brain death. METHODS: A phenomenographic method was
      chosen. Data collection (interviews) took place in Sweden and included fifteen
      nurses; one man and fourteen women, from six hospitals serving different
      geographic areas. RESULTS: The findings pertain to three domains: ICU nurses'
      perceptions of (1) their professional responsibility, (2) the role of the
      organisation regarding organ donation and (3) death and the diagnosis of brain
      death. CONCLUSION: The ambiguity and various perceptions of brain death diagnosis
      seem to be a crucial aspect when caring for a brain dead patient. The lack of
      structured and sufficient organisation also appears to be a limiting factor. Both
      these aspects are essential for the ICU nurses' opportunities to fulfil their
      professional responsibility during the organ donation process.

PMID- 21872473
TI  - The effects of high custom made shoes on gait characteristics and patient
      satisfaction in hemiplegic gait.
AB  - OBJECTIVE: To determine the effects of a temporary high custom made orthopaedic
      shoe on functional mobility, walking speed, and gait characteristics in
      hemiplegic stroke patients. In addition, interference of attentional demands and
      patient satisfaction were studied. DESIGN: Clinical experimental study. SETTING:
      University Medical Centre. PARTICIPANTS: Nineteen stroke patients (12 males; mean
      age 55 years (standard deviation (SD) 10 years); mean time post onset 3.6 months
      (SD 1.4 months)) with a spastic paresis of the lower extremity. MAIN OUTCOME
      MEASURES: Functional mobility was assessed with the timed up and go test, walking
      speed and gait characteristics were measured with clinical gait analysis and
      performed with and without a verbal dual task. Patient satisfaction was
      determined with a questionnaire. RESULTS: Walking with the high orthopaedic shoe
      resulted in improved functional mobility (22%; p<.001), walking speed (37%;
      p<.001) and gait characteristics compared to walking with normal shoes. The dual
      task interfered with functional mobility during walking. The interference was
      equally big for normal shoes as for the orthopaedic shoe. Patients evaluated
      walking with the high orthopaedic shoe as an improvement (p<.001). An average of
      84% reported improvements in foot lifting, swing progression, taking weight,
      confidence while walking, safety, walking distance and walking speed. CONCLUSION:
      In the early recovery phase after stroke, when regaining walking ability, a
      temporary high orthopaedic shoe can improve hemiplegic gait, even with dual task
      interference.

PMID- 21872474
TI  - Adjustments after an ankle dorsiflexion perturbation during human running.
AB  - In this study we investigated the effect of a mechanical perturbation of
      unexpected timing during human running. With the use of a powered exoskeleton, we
      evoked a dorsiflexion of the right ankle during its swing phase while subjects
      ran on a treadmill. The perturbation resulted in an increase of the right ankle
      dorsiflexion of at least 5 degrees . The first two as well as the next five steps
      after the perturbation were analyzed to observe the possible immediate and late
      biomechanical adjustments. In all cases subjects continued to run after the
      perturbation. The immediate adjustments were the greatest and the most frequent
      when the delay between the right ankle perturbation and the subsequent right foot
      touch-down was the shortest. For example, the vertical impact peak force was
      strongly modified on the first step after the perturbations and this adjustment
      was correlated to a right ankle angle still clearly modified at touch-down. Some
      late adjustments were observed in the subsequent steps predominantly occurring
      during left steps. Subjects maintained the step length and the step period as
      constant as possible by adjusting other step parameters in order to avoid
      stumbling and continue running at the speed imposed by the treadmill. To our
      knowledge, our experiments are the first to investigate perturbations of
      unexpected timing during human running. The results show that humans have a time
      dependent, adapted strategy to maintain their running pattern.

PMID- 21872476
TI  - Decreased expression of NDRG2 is related to poor overall survival in patients
      with glioma.
AB  - Members of the NDRG (N-Myc downstream-regulated) gene family have been shown to
      play a variety of roles in human malignancies. In the present study, we examined
      the expression of NDRG2 protein in glioma samples of WHO grades I-IV. We also
      investigated the association between NDRG2 expression and survival.
      Immunohistochemical analysis was used to measure NDRG2 protein expression in 316
      specimens of human glioma and 41 normal control tissues. Survival analysis was
      performed using the Kaplan-Meier method and Cox's proportional hazards model. We
      found that NDRG2 expression was reduced in glioma relative to normal tissue, and
      that NDRG2 expression decreased with increasing glioma grade. Kaplan-Meier
      analysis showed that patients without NDRG2 expression had a lower survival rate
      than other patients. Multivariate analysis showed that NDRG2 expression was an
      independent prognostic factor for overall survival of patients with glioma. The
      present study provides the first evidence that NDRG2 expression is decreased in
      gliomas, indicating that NDRG2 may play an inhibitory role during the development
      of gliomas. NDRG2 expression may also be a significant and independent prognostic
      indicator for glioma.

PMID- 21872475
TI  - Combined phylogenetic and genomic approaches for the high-throughput study of
      microbial habitat adaptation.
AB  - High-throughput sequencing technologies provide new opportunities to address
      longstanding questions about habitat adaptation in microbial organisms. How have
      microbes managed to adapt to such a wide range of environments, and what genomic
      features allow for such adaptation? We review recent large-scale studies of
      habitat adaptation, with emphasis on those that utilize phylogenetic techniques.
      On the basis of current trends, we summarize methodological challenges faced by
      investigators, and the tools, techniques and analytical approaches available to
      overcome them. Phylogenetic approaches and detailed information about each
      environmental sample will be crucial as the ability to collect genome sequences
      continues to expand.

PMID- 21872477
TI  - Fluorinated cannabinoid CB2 receptor ligands: synthesis and in vitro binding
      characteristics of 2-oxoquinoline derivatives.
AB  - Cannabinoid receptor 2 (CB2) plays an important role in human physiology and the
      pathophysiology of different diseases, including neuroinflammation,
      neurodegeneration, and cancer. Several classes of CB2 receptor ligands, including
      2-oxoquinoline derivatives, have been previously reported. We report the
      synthesis and results of in vitro receptor binding of a focused library of new
      fluorinated 2-oxoquinoline CB2 ligands. Twelve compounds, 13-1618, 19, 21-24, 27,
      and 28 were synthesized in good yields in multiple steps. Human U87 glioma cells
      expressing either hCB1 (control) or hCB2 were generated via lentiviral
      transduction. In vitro competitive binding assay was performed using [(3)H]CP
      55,940 in U87hCB1 and U87hCB2 cells. Inhibition constant (K(i)) values of
      compounds 13-16, 18, 19, 21-24, 27, and 28 for CB2 were >10,000, 2.8, 5.0, 2.4,
      22, 0.8, 1.4, >10,000, 486, 58, 620, and 2400 nM, respectively, and those for CB1
      were >10,000 nM. Preliminary in vitro results suggest that six of these compounds
      may be useful for therapy of neuropathic pain, neuroinflammatory diseases and
      immune disorders. In addition, compound 19, with its subnanomolar K(i) value,
      could be radiolabeled with (18)F and explored for PET imaging of CB2 expression.

PMID- 21872478
TI  - Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV
      agents.
AB  - A series of Matijing-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-L
      phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis
      B virus (HBV) activity in 2.2.15 cells. The IC(50) of compounds 14a (0.71 MUM),
      13c (2.85 MUM), 13b (4.37 MUM), etc. and the selective index of 13g (161.01), 13c
      (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were
      better than those of the positive control lamivudine (IC(50): 82.42 MUM, SI:
      41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity.

PMID- 21872479
TI  - Synthesis, antibacterial activities and molecular docking studies of Schiff bases
      derived from N-(2/4-benzaldehyde-amino) phenyl-N'-phenyl-thiourea.
AB  - A series of novel Schiff base derivatives have been designed and synthesized, and
      their biological activities were also evaluated as potential inhibitors of FabH.
      These compounds were assayed for antibacterial activity against Escherichia coli,
      Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. Compounds
      with potent antibacterial activities were tested for their E. coli FabH
      inhibitory activity. Compound 3v showed the most potent antibacterial activity
      with MIC of 1.56-6.25 MUg/mL against the tested bacterial strains and exhibited
      the most potent E. coli FabH inhibitory activity with IC(50) of 4.3 MUM. Docking
      simulation was performed to position compound 3v into the E. coli FabH active
      site to determine the probable binding conformation.

PMID- 21872480
TI  - A simplified analytical approach to estimate the parameters required for strength
      determination of HDR 192Ir brachytherapy sources using a Farmer-type ionization
      chamber.
AB  - Measuring the strength of high dose rate (HDR) (192)Ir brachytherapy sources on
      receipt from the vendor is an important component of a quality assurance program.
      Owing to their ready availability in radiotherapy departments, the Farmer-type
      ionization chambers are also used to determine the strength of HDR (192)Ir
      brachytherapy sources. The use of a Farmer-type ionization chamber requires the
      estimation of the scatter correction factor along with positioning error (c) and
      the constant of proportionality (f) to determine the strength of HDR (192)Ir
      brachytherapy sources. A simplified approach based on a least squares method was
      developed for estimating the values of f and M(s). The seven distance method was
      followed to record the ionization chamber readings for parameterization of f and
      M(s). Analytically calculated values of M(s) were used to determine the room
      scatter correction factor (K(sc)). The Monte Carlo simulations were also carried
      out to calculate f and K(sc) to verify the magnitude of the parameters determined
      by the proposed analytical approach. The value of f determined using the
      simplified analytical approach was found to be in excellent agreement with the
      Monte Carlo simulated value (within 0.7%). Analytically derived values of K(sc)
      were also found to be in good agreement with the Monte Carlo calculated values
      (within 1.47%). Being far simpler than the presently available methods of
      evaluating f, the proposed analytical approach can be adopted for routine use by
      clinical medical physicists to estimate f by hand calculations.

PMID- 21872481
TI  - Dosimetric feasibility study for an extracorporeal BNCT application on liver
      metastases at the TRIGA Mainz.
AB  - This study investigates the dosimetric feasibility of Boron Neutron Capture
      Therapy (BNCT) of explanted livers in the thermal column of the research reactor
      in Mainz. The Monte Carlo code MCNP5 is used to calculate the biologically
      weighted dose for different ratios of the (10)B-concentration in tumour to normal
      liver tissue. The simulation results show that dosimetric goals are only
      partially met. To guarantee effective BNCT treatment the organ has to be better
      shielded from all gamma radiation.

PMID- 21872482
TI  - Healing of donor defect after mandibular parasymphyseal block harvesting: a 6
      year computerized tomographic follow-up.
AB  - OBJECTIVES: A long-term survey on the healing potential of large-sized
      parasymphyseal osseous defects. PATIENTS AND METHODS: Ten patients, subjected to
      14 bilateral and 3 unilateral parasymphyseal bone harvesting for alveolar ridge
      augmentation, were selected for the retrospective chart review. CT scans were
      performed immediately before bone grafting, before implant insertion, and then
      once annually for 6 years, and the volumes of the bone defects at the buccal
      aspect in the healing process were measured using a software program. Volumes
      from the yearly measurements were then compared statistically. RESULTS: Volumes
      of both the intrasurgical defects, 0.77 (0.20) cc and of those in the one-year
      group, 0.60 (0.26) cc were statistically different from volumes of all the other
      time intervals (from 24 to 72 months) with all p-values less than 0.002 and
      0.004, respectively. The healing of osseous defects in the long-term radiographic
      survey (6 years) resulted in bony infill of 63%. CONCLUSION: For parasymphyseal
      defects of 0.7 cc, a maximum possible healing of two-thirds can be expected; a re
      harvesting procedure could be performed 24 months after early surgery, due to
      both the formation of a new buccal cortical plate and the achievement of a steady
      state of osseous remodelling.

PMID- 21872483
TI  - A rare case of iatrogenic gingival Kaposi's sarcoma.
AB  - Kaposi's sarcoma is an angioproliferative tumour rarely found in the oral cavity.
      We present the 3rd case of iatrogenic gingival Kaposi's sarcoma reported in the
      English-language literature which developed in a young patient 5 years after a
      renal transplant and discuss their histological features and differential
      diagnosis.

PMID- 21872484
TI  - Facial movement before and after masseteric-facial nerves anastomosis: a three
      dimensional optoelectronic pilot study.
AB  - To quantify the effects of facial palsy reanimation, 14 patients aged 17-66 years
      were analysed. All patients had unilateral facial paralysis, and were candidates
      for surgical masseteric to facial nerve anastomosis. Two patient groups were
      measured: seven patients were waiting for surgery, the other seven patients had
      already been submitted to surgery, and had regained facial mimicry. Each patient
      performed three facial animations: brow raise; free smile; lip purse. These were
      recorded using an optoelectronic motion analyser. The three-dimensional
      coordinates of facial landmarks were obtained, their movements were computed, and
      asymmetry indices calculated (differential movements between the two hemi-faces:
      healthy and paretic/rehabilitated). Before surgery, mobility was larger in the
      healthy than in the paretic side; after surgery, the differences were reduced
      (brow raise and lip purse), or even reversed (smile). Before surgery, lip purse
      was performed with significant labial asymmetry (p=0.042; larger healthy side
      movement). After surgery, asymmetry indices reduced. Total labial asymmetry
      during smiling was significantly different from 0 before surgery (p=0.018, larger
      healthy side movement). After surgery, all asymmetry indices became non
      significant. Before surgery the lateral displacements of all labial landmarks
      were towards the healthy side, while they normalized after surgery.

PMID- 21872485
TI  - Accelerating the aesthetic benefit of wound healing by triterpene.
AB  - Intention of the study (EudraCT No 2009-017418-56) is a proof of aesthetic
      benefit of triterpene treatment in superficial wounds. In an open, prospective,
      controlled, randomized, blindly evaluated multicentre phase II clinical trial a
      triterpene ointment (OG-S10) is compared intra individually with a state-of-the
      art moist wound healing dressing (Mepilex((r))) in split thickness skin graft
      donor sites. The graft wound areas at the upper leg were divided into two equal
      halves, one proximal and one distal site. Decided by randomization the one site
      was treated with triterpene and the other in comparison with moist dressing.
      Triterpene treatment went on for 14 days as covering the wound at every change of
      wound dressing with the ointment (100 mg/cm(2)). The comparative treatment went
      on as covering the site by this dressing alone. The outcome of these different
      treatments was evaluated by two blindly observing distant experts on the basis of
      photographs of the wound healing progress. Photographs were taken day 14, 3 month
      and 1 year after treatment. The only criterion for evaluation of the two sites
      was similarity of the wound area to the surrounding skin in terms of colour and
      texture: which of the two sites, the proximal or the distal, was aesthetically
      superior in normal skin appearance after 14 days at the end of treatment, after 3
      month of follow up and 1 year after treatment? The descriptive comparison is
      demonstrating quite a remarkable advantage of the ointment versus the moist wound
      dressing in promoting wound healing: even having in mind the small number of 24
      patients within the protocol, the superiority of aesthetic benefit by triterpene
      treatment after 14 days (22 out of 24 patients), after 3 month (15 out of 19
      patients) and after 1 year (8 out of 10 patients) is obvious.

PMID- 21872486
TI  - Aesthetic satisfaction scoring - introducing an aesthetic numeric analogue scale
      (ANA-scale).
AB  - To objectively and reproducibly assess the outcome of aesthetic procedures
      remains one of the major, unmet challenges in maxillo-facial and plastic surgery.
      Frequently employed scoring systems for the evaluation of aesthetic procedures
      are confounded by observer bias, be it that of the patient or of the surgeon. A
      new approach of pragmatic and simple scoring is the ANA [Aesthetic Numeric
      Analogue] scale, which facilitates the objective, reproducible, standardized and
      internationally uniform evaluation of aesthetic procedure outcome by converting
      all ratings for any kind of aesthetic procedures from a subjective value to an
      objective figure. The intention of the ANA-scale is to relate aesthetic
      satisfaction from wording to figures and by this create a rating system. The
      study is arranging matching pairs of verbal description and figures to finally
      queue up generating a scale. The clinical feasibility of this rating system is
      demonstrated in a surgical case. As a detail of the results the influence of the
      viewer's age to the aesthetic benefit assessment is obvious. In summary the ANA
      scale looks to be a tool useful in individual treatment protocols as well as
      analysis of different techniques of aesthetic surgery for rating of the pure
      aesthetic satisfaction of the patients.

PMID- 21872487
TI  - The effect of current used bone substitution materials and platelet-rich plasma
      on periosteal cells by ectopic site implantation: an in-vivo pilot study.
AB  - The aim of this study was to investigate de novo bone formation following ectopic
      site implantation of bone substitutes covered by periosteum, with and without the
      application of autologous platelet-rich plasma (PRP). Twenty-four weeks after
      subcutaneous implantation of various bone substitutes (bovine hydroxyapatite
      (bHAP), phycogenic hydroxyapatite (pHAP), and bioglass (BG)) in 35 mini-pigs,
      bone regeneration rates were compared microradiographically and histologically.
      Without PRP, bHAP showed a mean de novo bone formation of 32.41%+/-29.99, in
      contrast to the other substitute materials where no mineralization could be
      detected. In combination with PRP, in the bHAP (63.61%+/-12.98; p+/-0.03) and
      pHAP (34.37+/-29.38; p=0.015) group, significantly higher de novo bone formation
      was ascertained than without PRP. No ossification could be detected in the BG
      group. In conclusion, bHAP and pHAP bone substitutes in combination with PRP
      showed a significant positive effect on periosteal cells by de novo bone
      formation after ectopic, subcutaneous, low-vascular site implantation.

PMID- 21872488
TI  - Do Asian-American women who were maltreated as children have a higher likelihood
      for HIV risk behaviors and adverse mental health outcomes?
AB  - OBJECTIVES: This study is the first to systematically investigate whether
      multiple child maltreatment is associated with HIV risk behaviors and adverse
      mental health outcomes among Asian-American women. METHODS: We conducted a cross
      sectional study of unmarried Chinese, Korean, and Vietnamese women (n = 400),
      aged 18 to 35, who are identified as children of immigrants, using computer
      assisted survey interviews. RESULTS: Approximately 7 in 10 women reported having
      been maltreated as a child and 6.8% reported any type of sexual abuse. Only 15%
      of our sample reported having sex at age 16 or before, yet almost 60% had ever
      engaged with potentially risky sexual partners. Contrary to the findings from
      previous studies of White and Black women, sexual abuse plus other maltreatment
      was not associated with HIV risk behaviors among Asian-American women. However,
      it was associated with a marked increase in depression, lifetime suicidal
      ideation, and suicide attempts. A higher education level was associated with
      increased odds of HIV risk behaviors, including ever having had anal sex and ever
      having potentially risky sexual partners. CONCLUSION: There was no evidence
      indicating that multiple child maltreatment was linked with HIV risk behaviors,
      but it exhibited a robust association with poor mental health outcomes. These
      empirical patterns of internalizing trauma, suffering alone, and staying silent
      are in accord with Asian-cultural norms of saving face and maintaining family
      harmony. The prevention of multiple child maltreatment may reduce high levels of
      depression and suicidal behaviors in this population. It is urgent to identify
      victims of multiple child maltreatment and provide culturally appropriate
      interventions.

PMID- 21872489
TI  - Geometry of saccular, side-branch cerebral aneurysms: implications for treatment.
AB  - BACKGROUND: Saccular, side-branch aneurysms are cerebral aneurysms that occur at
      the junction between a major intracranial artery and a smaller vessel that
      originates from this parent artery. The geometry of this group of aneurysms was
      investigated to determine the location of the side branch in relation to the
      parent vessel or aneurysm neck. METHODS: From a series of microsurgically clipped
      cerebral aneurysms, 121 side-branch aneurysms had detailed imaging studies and
      operative records that could be analyzed to determine side-branch vessel origin
      in relation to the aneurysm neck. RESULTS: The distribution of aneurysms (N) and
      the number in which the side-branch originated from the parent artery (PA) were:
      internal carotid ophthalmic (N = 37; PA = 11); internal carotid-superior
      hypophyseal (N = 2; PA = 2); internal carotid-posterior communicating (N = 28; PA
      = 11); internal carotid-anterior choroidal (N = 5; PA = 1); main stem of the
      middle cerebral artery (N = 13; PA = 6); main stem of the anterior cerebral
      artery (N = 7; PA = 6); secondary branch of the middle cerebral artery (N = 8; PA
      = 7); secondary branch of the anterior cerebral artery (N = 1; PA = 0); vertebral
      posterior inferior cerebellar artery (N = 11; PA = 5); basilar-anterior inferior
      cerebellar artery (N = 2; PA = 1); and basilar-superior cerebellar artery (N = 7;
      PA = 5). CONCLUSIONS: Regardless of whether these observations reflect the
      universe of cerebral aneurysms, a certain percentage of this group of aneurysms
      will have the side-branch vessel originate from the aneurysm neck. This incidence
      will likely be influenced by aneurysm location and other factors. Protection of
      these important vessels from occlusion during endovascular management will
      require sophisticated endovascular techniques. If these measures are either
      unavailable or prove unsuccessful, then clipping will be needed if the side
      branch vessel originates from the aneurysm neck and its preservation is critical.

PMID- 21872490
TI  - Volatile agents for cardiac protection in noncardiac surgery: a randomized
      controlled study.
AB  - OBJECTIVE: Volatile anesthetics reduce the risk of myocardial infarction and
      mortality in coronary artery surgery. Recently, the American College of
      Cardiology/American Heart Association Guidelines suggested the use of volatile
      anesthetic agents for the maintenance of general anesthesia during noncardiac
      surgery in patients at risk for perioperative myocardial ischemia, but no
      randomized experience to document the cardioprotective effects of these agents
      exists in this setting. Therefore, the authors performed a prospective,
      randomized, controlled trial to compare the effects of sevoflurane versus total
      intravenous anesthesia, in terms of postoperative cardiac troponin I release in
      patients undergoing noncardiac surgery. DESIGN: A randomized, controlled trial.
      SETTING: A teaching hospital. PARTICIPANTS: Eighty-eight consecutive patients
      undergoing noncardiac surgery. INTERVENTIONS: Patients were allocated randomly to
      receive either volatile anesthetic (44 patients) as the main anesthetic agent or
      total intravenous anesthesia (TIVA) (44 patients). MEASUREMENTS: Postoperative
      cardiac troponin I release was measured as a marker of myocardial necrosis.
      Patients with detectable postoperative troponin I in the sevoflurane group
      (12/44, 27.3%) were similar to those in the propofol group (9/44, 20.5%; p =
      0.6). There was no significant reduction of postoperative median peak cTnI
      release (0.16 +/- 0.71 ng/mL in the sevoflurane group compared with the TIVA
      group, 0.03 +/- 0.08 ng/mL; p = 0.4). Three patients died at the 1-year follow-up
      for noncardiac causes (2 in the TIVA group). CONCLUSIONS: In the authors'
      experience, patients undergoing noncardiac surgery did not benefit from
      anesthesia based on halogenated anesthetics. Further studies are necessary to
      evaluate the cardioprotective effects of volatile agents in noncardiac surgery.

PMID- 21872491
TI  - Cardiac thrombosis in a patient during extracorporeal life support.

PMID- 21872492
TI  - Correlation between mineralization and mechanical strength of the subchondral
      bone plate of the humeral head.
AB  - BACKGROUND: One of the main problems in shoulder arthroplasty is the fixation of
      the prosthesis, where the subchondral bone plate plays an important role.
      Subchondral mineralization patterns represent the loading history of a joint and
      give information about the individual biomechanical situation. The objective of
      this study was to determine if a correlation between subchondral mineralization
      and mechanical strength in the humeral head exists. MATERIALS AND METHODS:
      Subchondral mineralization of 32 shoulder specimens was investigated by use of
      computed tomography (CT) osteoabsorptiometry. The previously dissected specimens
      were scanned axially in a CT scanner, and the obtained data sets were transferred
      into an image analyzing system. Maximum intensity projection was used to evaluate
      the density distribution of the subchondral bone plate. To get information about
      mechanical strength of the subchondral bone, each specimen was investigated at 29
      predefined points by means of an indentation-testing machine. RESULTS: The
      maximum strength was mostly detected in the center (monocentric pattern) or in
      anterior and posterior areas of the articular surface (bicentric pattern). The
      distribution of mineralization showed the same 2 reproducible patterns. The
      coefficient of correlation between mechanical strength and mineralization shown
      on CT was between 0.59 and 0.96. The obtained information was statistically
      significant (P < .01). CONCLUSION: Mechanical strength and subchondral
      mineralization in the humeral head are significantly associated (P < .01). As a
      consequence of these findings, CT osteoabsorptiometry can be indirectly used to
      give information about bone quality in vivo. Our findings could be useful for the
      development of new fixation methods in shoulder surgery (eg, humeral resurfacing
      arthroplasty).

PMID- 21872493
TI  - Minimally invasive percutaneous plating of proximal humeral shaft fractures with
      the Proximal Humerus Internal Locking System (PHILOS).
AB  - BACKGROUND: This study evaluated our results after minimally invasive
      percutaneous plating of proximal humeral shaft fractures with the Proximal
      Humerus Internal Locking System (PHILOS, Synthes, Switzerland). MATERIALS AND
      METHODS: Between 2005 and 2008, 15 patients with unilateral displaced proximal
      humeral shaft fractures were treated and followed up over a median period of 27
      months (range, 12-38 months). The final follow-up included anteroposterior and
      lateral x-rays, range of shoulder motion, pain by visual analog scale (VAS), the
      Constant-Murley shoulder score, the Disabilities of Arm, Shoulder and Elbow
      (DASH) score, and the Short Form 36 (SF36) assessment. RESULTS: No intraoperative
      or postoperative complications occurred. No secondary fracture displacement or
      radial neuropathy was observed postoperatively. One patient had open reduction
      and internal fixation for pseudoarthrosis 16 months after the initial surgery. At
      the final follow-up, the median range of motion of the operated shoulder was
      flexion, 145 degrees ; extension, 45 degrees ; internal rotation, 40 degrees ;
      external rotation, 70 degrees ; and abduction, 135 degrees . Median results on
      outcome assessments were VAS pain score, 0 points; Constant-Murley score, 74
      points, representing 87.5% of the median Constant-Murley score of the unaffected
      shoulder; DASH score, 34 points, and the SF36, 83 points. CONCLUSION: Minimally
      invasive percutaneous plating with the PHILOS offers a valid option in the
      treatment of proximal humeral shaft fractures with comparable rates of nonunion
      and lower rates of radial neuropathy compared with open procedures. Furthermore,
      the results indicate that this method is associated with lower rates of wound
      infection and a shorter stay in the hospital for the patient.

PMID- 21872494
TI  - Resection arthroplasty for septic arthritis of the sternoclavicular joint.
AB  - BACKGROUND: Treatment for septic arthritis of the sternoclavicular (SC) joint
      with concomitant osteomyelitis of the clavicle often requires joint resection
      rather than simple incision and drainage. We evaluated the effectiveness of
      resection arthroplasty for patients with septic arthritis of the SC joint.
      METHODS: We retrospectively reviewed 10 patients who underwent resection
      arthroplasty for SC joint septic arthritis between 1996 and 2008. The mean
      patient age was 52.8 +/- 10.5 years (range, 40-72 years), the mean symptom
      duration before surgery was 16.9 days (range, 2-60 days), and the mean follow-up
      period was 35.4 +/- 42.2 months (range, 10-108 months). Diagnoses were based on
      physical examination, laboratory tests, and radiologic studies including magnetic
      resonance imaging. Each patient had concomitant osteomyelitis of the clavicle. In
      addition, 4 patients had mediastinitis and 1 had osteomyelitis of the adjacent
      ribs. All patients underwent SC joint resection and intramedullary ligament
      reconstruction, followed by intravenous antibiotics for 4 to 8 weeks.
      Intraoperative cultures were positive in 6 patients. RESULTS: All infections
      resolved, with only 1 patient having complications-systemic sepsis and pneumonia.
      The mean ranges of motion were 146 degrees  of forward flexion (range, 135
      degrees -155 degrees ) and 48 degrees  of external rotation (range, 40 degrees 
      55 degrees ), with the internal rotation level ranging from T5 to L3. The mean
      superior migration of the clavicle was 1.5 mm (range, 0-4 mm), and the mean
      visual analog pain score was 1.4 +/- 0.7 (range, 0-2). CONCLUSION: Resection
      arthroplasty in patients with septic SC joints results in relatively good
      shoulder function.

PMID- 21872495
TI  - Extranodal Rosai-Dorfman disease presenting as an isolated glenoid lesion in a
      high school athlete.

PMID- 21872496
TI  - Functional outcome of hemiarthroplasty compared with reverse total shoulder
      arthroplasty in the treatment of rotator cuff tear arthropathy.
AB  - BACKGROUND: Hemiarthroplasty was the treatment of choice for rotator cuff tear
      arthropathy (CTA) before the introduction of the reverse total shoulder
      arthroplasty (RTSA). The purpose of this study was to compare our outcomes for
      hemiarthroplasty with those for RTSA. METHODS: The records of patients with the
      diagnosis of CTA who had received either a hemiarthroplasty or RTSA from 1997 to
      2007 were reviewed. A minimum of 2 years' follow-up was required. Active shoulder
      elevation, external rotation, internal rotation, and Shoulder Pain and Disability
      Index (SPADI) scores were obtained. Statistical analysis was performed comparing
      function, pain, and range of motion of hemiarthroplasty patients with RTSA
      patients. RESULTS: We identified 56 shoulder arthroplasties in 50 patients with a
      minimum of 2 years' follow-up. There were 20 hemiarthroplasties and 36 RTSAs
      performed. The mean follow-up was 4.4 years (range, 2-12 years) in the
      hemiarthroplasty group and 3 years (range, 2-5 years) in the RTSA group. The mean
      age in the hemiarthroplasty group was 64 years versus 72 years in the RTSA group
      (P < .05). SPADI scores improved in both groups. However, after follow-up of 2
      years or greater, the mean SPADI scores were significantly better (lower) in the
      RTSA group (34) than in the hemiarthroplasty group (58) (P = .005). Active
      elevation was significantly better in the RTSA group at all postoperative time
      periods. The complication rate for both groups was 25%. CONCLUSIONS: RTSA
      performs better than hemiarthroplasty in terms of pain relief, function, and
      active elevation at 2-year follow-up.

PMID- 21872497
TI  - Staging laparoscopy in the management of gastric cancer: a population-based
      analysis.
AB  - BACKGROUND: Staging laparoscopy can detect radiographically occult peritoneal
      metastases and prevent futile laparotomy in patients with gastric adenocarcinoma.
      We sought to assess the use of staging laparoscopy for gastric adenocarcinoma in
      a cohort of older patients and to compare outcomes after laparoscopy alone with
      nontherapeutic laparotomy. STUDY DESIGN: Using Surveillance, Epidemiology and End
      Results (SEER) population-based cancer registry data linked with Medicare claims,
      we identified patients aged 65 or older diagnosed with gastric adenocarcinoma
      between 1998 and 2005. We defined staging laparoscopy as a laparoscopic procedure
      from 1 month before the date of diagnosis until death and futile laparotomy as a
      laparotomy in the absence of a therapeutic intervention. We examined trends in
      the use of staging laparoscopy and compared outcomes between patients who
      underwent staging laparoscopy alone and those who had a futile laparotomy.
      RESULTS: Of 11,759 patients with gastric adenocarcinoma, 6,388 (54.3%) had at
      least 1 surgical procedure. Staging laparoscopy was performed in 506 (7.9%)
      patients who had any surgery, and 151 (29.8%) of these patients did not have a
      subsequent therapeutic intervention. Patients who underwent staging laparoscopy
      alone had a significantly lower rate of in-hospital mortality (5.3% vs 13.1%, p <
      0.001) and shorter length of hospitalization (2 vs 10 days, p < 0.001) than
      patients who had futile laparotomy. CONCLUSIONS: Our findings in this large,
      population-based cohort suggest that staging laparoscopy is used infrequently in
      the management of older patients with gastric adenocarcinoma. Increased use of
      staging laparoscopy could reduce the substantial morbidity and mortality
      associated with nontherapeutic laparotomy.

PMID- 21872498
TI  - c-Jun is involved in interstitial cystitis antiproliferative factor (APF)-induced
      growth inhibition of human bladder cancer T24 cells.
AB  - OBJECTIVE: To uncover the role of c-Jun, a proto-oncogene, in inhibitory effects
      of antiproliferative factor (APF) on tumor cell growth. MATERIALS AND METHODS:
      Expression of c-Jun was analyzed by Western blotting in 45 clinical specimens (30
      tumorous tissues and 15 paired non-tumorous tissues) and 3 bladder cancer cell
      lines. APF-responsive T24 transitional carcinoma bladder cells were treated with
      APF or mock control. Cell proliferation was measured by 3-(4,5-dimethylthiazolyl
      2)-2,5-diphenyltetrazolium bromide (MTT) assay. Change of c-Jun expression was
      detected by RT-PCR and Western blotting. The influence of c-Jun on APF treatment
      was evaluated by transient transfection of c-Jun and MTT assay in T24 cells.
      RESULTS: c-Jun was significantly higher in invasive bladder cancer tissues and
      cell lines. T24 cells treated with APF had decreased c-Jun expression and
      suppressed cell growth. More importantly, ectopic c-Jun attenuated APF inhibitory
      effects on cell growth. CONCLUSIONS: These observations suggest that c-Jun is
      involved in APF-mediated inhibition for bladder tumor cell growth, as potential
      target of APF in patients with aggressive bladder carcinoma.

PMID- 21872499
TI  - Low risk prostate cancer in men >= 70 years old: to treat or not to treat.
AB  - OBJECTIVES: Prostate cancer (CaP) in the aging male will become an increasingly
      important and controversial health care issue. We evaluated the outcomes between
      a variety of treatments for low-risk CaP in patients 70 years of age and older.
      METHODS AND MATERIALS: A total of 3,650 men diagnosed with CaP between 1989 and
      2009 were identified in the Center for Prostate Disease Research database to be
      70 years of age or older at time of diagnosis. Of these patients, 770 men met the
      D'Amico criteria ([13]) for low-risk disease and were treated with radical
      prostatectomy, external beam radiation therapy, or watchful waiting. Cox
      proportional hazard models were used to compare clinicopathologic features across
      treatment groups. Kaplan-Meier analysis was used to compare biochemical
      recurrence-free, progression-free, and overall survival. RESULTS: Of the 770
      patient cohort, 194 (25%) chose radical prostatectomy, 252 (33%) chose external
      beam radiation therapy, and 324 (42%) were initially managed by watchful waiting
      with 110 (34%) of this subset ultimately undergoing secondary treatment. The
      median follow-up was 6.4 years. There were no significant differences in
      distributions of race/ethnicity, number of medical comorbidities, or clinical
      stage across the treatment groups. Patients managed on watchful waiting without
      secondary treatment had the poorest overall survival on Kaplan-Meier analysis (P
      = 0.0001). Additionally, multivariate analysis confirmed this result for watchful
      waiting without secondary treatment as being a statistically significant
      predictor of overall mortality (HR 1.938, P = 0.0084).

PMID- 21872500
TI  - Maxillary sinus floor augmentation in patients with maxillary sinus pseudocyst:
      case report.
AB  - The maxillary sinus floor elevation procedure has gained popularity with
      predictable results, and is a safe, acceptable technique for bone augmentation,
      providing a base for dental implant treatment. Faint radiopaque lesions at the
      base of the maxillary sinus are frequent diagnoses on radiographs and must be
      identified during dental implant planning. Pseudocysts classically appear
      hemispheric, homogeneously opaque, and well delineated in panoramic and
      periapical radiographs. The great majority of these lesions are asymptomatic and
      do not require surgical treatment. In this case report, we present 4 patients who
      had a maxillary sinus floor elevation procedure using either crestal or lateral
      approaches in the presence of antral pseudocysts. No complications were
      encountered during follow-up periods in these patients and all implants are
      functioning successfully.

PMID- 21872501
TI  - Two-stage split-crest technique with ultrasonic bone surgery for controlled ridge
      expansion: a novel modified technique.

PMID- 21872503
TI  - Nicorandil-induced oral ulceration: report of 3 cases and review of the Japanese
      literature.
AB  - Nicorandil-induced oral ulceration in 3 Japanese patients is reported. The
      patients were men aged 86, 81, and 91 years. Ulcers of 15, 10, and 12 mm in
      diameter, respectively, were observed at the border of all of the patients'
      tongues. These were painful and persistent but not indurated. Irritation by the
      teeth or dentures was not evident. They had been administered nicorandil at a
      dose of 15 mg for 22, 54, and 90 months, respectively; therefore, ulceration
      induced by nicorandil was suspected. In consultation with the doctor, nicorandil
      was withdrawn. The ulcers disappeared 5, 8, and 9 weeks, respectively, after the
      cessation of nicorandil. No relapse of the ulcer was noted. The findings suggest
      that these were the examples of nicorandil-induced oral ulceration.

PMID- 21872505
TI  - Isolation of mesenchymal stem cells from the mandibular marrow aspirates.
AB  - OBJECTIVE: The aim of this study was to determine if mesenchymal stem cells
      (MSCs) could be obtained from mandible marrow aspirates. STUDY DESIGN: In 5
      patients, 10 mL marrow aspirates were obtained from both the mandible and the
      iliac crest. Second passage MSCs were characterized by fluorescence-activated
      cell sorting (FACS) analysis using MSC-specific cell surface marker, and fifth
      passage cells were differentiated into 3 mesenchymal tissues in vitro. RESULTS:
      Average total cell yields of MSCs were 2.8 +/- 1.8 * 10(5) per 10 mL marrow
      aspirates from the mandible. Immunophenotypes of MSCs isolated from the mandible
      and iliac crest were highly similar, as indicated by FACS analysis.
      Differentiation into mesodermal cell types, such as osteocytes, chondrocytes, and
      adipocytes, was successfully achieved in all MSC isolates from all aspirates.
      CONCLUSIONS: The MSCs can be isolated from the mandibular aspirates, providing an
      alternative accessible source of MSCs for the treatment of future dental and
      craniomaxillofacial diseases.

PMID- 21872507
TI  - Oral and maxillofacial myiasis: a case series and literature review.
AB  - OBJECTIVE: The aim of this study was to describe a series of 10 cases of oral
      maxillofacial myiasis, discussing its main features, demographic distribution,
      and treatment aspects. STUDY DESIGN: A retrospective study was carried out
      involving male and female patients of any age with oral-maxillofacial myiasis.
      The sample was determined by spontaneous demand at the emergency ward of a
      hospital between January 2005 and January 2011 (6 years). After treatment of each
      case, data were gathered on the presence of associated systemic disorders, time
      elapsed since onset of the disease, and treatment established. A review of the
      literature on this topic was also carried out. RESULTS: The sample was made up of
      10 patients, all treated with surgical debridement whether or not associated with
      the use of oral ivermectin. Mean time elapsed since the onset of the disease
      ranged from 4 to 36 months. The middle third of the face was the most frequently
      affected region (7 cases). Oral-maxillofacial myiasis predominantly affected the
      male gender (70%). CONCLUSIONS: Oral-maxillofacial myiasis affects individuals
      with poor hygiene and neurologic and/or psychologic alterations. It occurs
      predominantly in countries near the tropics. The treatment of choice is surgical
      debridement.

PMID- 21872509
TI  - Caldwell-Luc procedure for retrieval of displaced root in the maxillary sinus.
AB  - OBJECTIVE: The aim of this study was to describe the standard diagnostic
      procedure and the application of the Caldwell-Luc approach for the retrieval of a
      displaced root from the maxillary sinus and to share our experience in treating
      this complication. STUDY DESIGN: Twenty-four patients with a fractured root
      accidentally displaced into the maxillary sinus were referred by general dentists
      to our department from 2005 to 2008. All were managed by a standardized
      diagnostic procedure and a Caldwell-Luc approach. We recorded the age of each
      patient, the gender, the tooth, the size of root fragment, the type of
      displacement the delay between displacement and retrieval, the length of
      operating time, and any complications. RESULTS: Over a 4-year period, we treated
      24 patients, 14 being male and 10 female. Ages ranged from 14 to 55 years
      (average 26.4). The commonest tooth involved was the maxillary first molar; the
      length of the root fragments ranged from 3 to 7 mm. Seventeen of these roots were
      mobile and 7 fixed (4 being located between the sinus membrane and the bone and 3
      immobilized by the sinus membrane. Twenty-three of the operations were completed
      in 30 minutes, and only 2 patients had a temporary complication of sinusitis. No
      infraorbital paresthesia occurred. CONCLUSIONS: The standardized diagnostic
      procedure and Caldwell-Luc approach for the retrieval of a displaced root form
      the maxillary sinus is a safe, simple, and fast method with minimal
      complications.

PMID- 21872510
TI  - In vitro antimicrobial activity of maleic acid and ethylenediaminetetraacetic
      acid on endodontic pathogens.
AB  - OBJECTIVE: The aim of this study was to evaluate the antimicrobial efficacy of 7%
      maleic acid (MA) and 17% ethylenediaminetetraacetic acid (EDTA) in elimination of
      Enterococcus faecalis, Candida albicans, and Staphylococcus aureus at different
      time intervals. STUDY DESIGN: Transfer culture of microbial strains were used for
      inoculum preparation and determination of time-kill assay. The viability counts
      of 7% MA and 17% EDTA suspensions were performed at 0, 2, 4, 6, 12, and 24 hours.
      Assay results were analyzed by determining number of strains that yielded log(10)
      CFU/mL of -1 compared with counts at 0 hours, for test medicaments at time
      intervals. Medicaments were considered to be microbicidal at a minimum inhibitory
      concentration that reduced original inoculum by >3 log(10) CFU/mL (99.9%) and
      microbiostatic if inoculum was reduced by <3 log(10) CFU/mL. Statistical analysis
      was performed using chi-square and Fisher exact tests as well as Friedman test
      for comparison of the time interval within the MA and EDTA groups. RESULTS: At
      all time intervals, there was no significant difference between MA and EDTA for
      all of the organisms (P > .05). However, within the MA and EDTA groups at various
      time intervals, there were significant differences (P < .001). CONCLUSIONS:
      Equivalent antimicrobial activity was observed by MA and EDTA against all of the
      organisms tested at various periods.

PMID- 21872513
TI  - Evaluation of pH and calcium ion release in capseal I and II and in two other
      root canal sealers.
AB  - OBJECTIVE: The aim of this study was to compare the pHs and calcium ion releases
      of newly developed, calcium phosphate-based root canal sealers (Capseal I and II)
      with those of Sealapex (SA) and Sankin Apatite Root Sealer III (SARS III). STUDY
      DESIGN: Each material (n = 10) was mixed, inserted into polyvinyl chloride (PVC)
      tubes, and immersed in a vial containing deionized water. The control group
      consisted of empty PVC tubes (n = 10). The pHs and calcium ion releases were
      measured by pH meter and ICP-AES (inductively coupled plasma atomic emission
      spectrometer) at 24 hours and 96 hours, and at 7, 15, and 28 days. The results
      were analyzed with the Kruskal-Wallis test. RESULTS: Capseal I and II produced
      pHs and calcium ion releases higher than or equal to those of SA and SARS III (P
      < .05). CONCLUSIONS: Capseal I and II resulted in higher alkalinity and higher
      calcium ion releases than SA and SARS III.

PMID- 21872515
TI  - Cervicitis in adolescents: do clinicians understand diagnosis and treatment?
AB  - BACKGROUND: Cervicitis is widespread, but no studies have examined cervicitis in
      accordance with established guidelines for diagnosis and treatment. Study
      objectives were to describe adherence to Centers for Disease Control and
      Prevention guidelines for diagnosis and treatment of cervicitis within an
      adolescent population and to compare factors associated with adherence to
      guidelines in a primary care setting and the Emergency Department. METHODS: Data
      were collected as part of a retrospective chart review of evaluation, diagnosis,
      and treatment of STI in adolescent women in an outpatient setting. Participant
      charts were eligible for review if they were 12-21 years of age and were given an
      ICD-9 and chart diagnosis of cervicitis. Two primary outcome variables: meeting
      cervicitis guidelines and correct treatment among those meeting cervicitis
      guidelines (no/yes) were utilized; the study controlled for age, race, venue,
      past infection with chlamydia or gonorrhea. RESULTS: Subjects (n = 365) were
      examined for the primary outcome variables and 75.1% (274/365) met at least one
      criterion for cervicitis. Of these, 166 (60.9%: 166/274) subjects were found to
      meet criteria for cervicitis alone, versus subjects meeting criteria for both
      cervicitis and pelvic inflammatory disease (PID) (39.4%: 108/274). The majority,
      89.3%, (326/365) were treated for both chlamydia and gonorrhea, but only 64.7%
      (211/326) were treated correctly for both infections. CONCLUSIONS: Our findings
      suggest that knowledge deficits exist in diagnosis and treatment of cervicitis in
      adolescent patients and in differentiating between cervicitis and PID.
      Educational tools, simulated patient exercises, and order sets may be warranted
      for quality improvement to allow for improved care of this at risk sexually
      active population.

PMID- 21872516
TI  - Fertility preservation in prepubertal girls prior to chemotherapy and
      radiotherapy--review of the literature.
AB  - Significant improvement in the survival rates of children with pediatric cancers
      has been achieved over the last 25 years, so the number of long-term survivors is
      increasing and their subsequent quality of life is of increasing importance. One
      of the most serious side effects of chemotherapy or radiotherapy is damage to the
      ovarian function, which can lead to loss of fertility. The degree of this damage
      depends on the substances used, the dose of radiotherapy reaching the ovaries,
      and the age of the girl at the time of treatment. Up to now, the only established
      method of fertility preservation has been cryoconservation of fertilized egg
      cells or embryos, but this is not possible in prepubertal girls because of their
      sexual immaturity. Removal of ovarian tissue and subsequent cryoconservation with
      the option of later orthotopic retransplantation is therefore an option to these
      girls. This method can lead to pregnancy and birth in adult women. Up to now
      there are no studies about the retransplantation of ovarian tissue which was
      removed before puberty. Displacement of the ovaries away from the radiation field
      before radiation to the pelvic area can be considered; however, the data is
      controversial. One problem in the use of fertility preservation methods in these
      very young patients is that they undergo procedures which, because of their age,
      they mostly do not understand and the parents must make a decision based on the
      assumed later wishes of their daughter.

PMID- 21872517
TI  - Management of vaginal agenesis.
AB  - Rokitansky syndrome and complete androgen insensitivity syndrome are the most
      common causes of vaginal agenesis. Treatment should be deferred until adolescence
      to allow informed consent and compliance. The best treatment for vaginal agenesis
      remains controversial although vaginal dilation therapy is still widely
      considered the first line treatment because success rates are high and associated
      risks are low. A variety of surgical options are also available, each with
      enthusiastic proponents. Long-term outcome studies on most surgical techniques,
      however, are still lacking and until recently most studies have reported on
      success rate in terms of anatomical success only, without including sexual
      function. Moreover, the medical literature lacks prospective comparative outcome
      studies, meaning that current choice of surgical procedure relies greatly on the
      surgeon's preference and experience.

PMID- 21872518
TI  - Insight: prolonged vaginal bleeding during central precocious puberty therapy
      with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism
      and management plan.
AB  - We have previously described our data collected after administration of
      gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in
      premenarchal girls suffering from idiopathic central precocious puberty.(1) We
      have explained the recurrent episodes of bleeding due to discontinuation of the
      estrogen support of the proliferative and stable endometrium. The recognition in
      recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to
      stimulate prostaglandin production and the known role of prostaglandins in
      irregular vaginal bleeding prompted us to seek alternative explanations to our
      data. We suggest considering a potential clinical use of combination therapies of
      GnRH agonists and prostanoid receptor antagonists to treat central precocious
      puberty.

PMID- 21872519
TI  - [Joint home follow-up of a patient with complicated diabetes mellitus by the case
      manager and the community nurse: II].
AB  - This is a continuation of the article published in this journal (Enfermeria
      Clinica), entitled "Integral approach by the case manager and the community nurse
      to a complex case of diabetes mellitus in the home". We present the case of a 76
      year- old patient with long-term and clinically complex Diabetes Mellitus. The
      patient was taking part in the Primary Care home care program. This article
      describes the follow-up of the case in which new complications appeared in the
      right limb, which led to the amputation of the second limb. A new evaluation
      following Virginia's Henderson model was performed six months after the initial
      care plan. Nursing diagnoses were made following the North American Nursing
      Diagnosis Association (NANDA). These diagnoses led to changes in objectives and
      performance criteria using, nursing outcomes classification (NOC) and nursing
      interventions classification (NIC). One of the results obtained was the
      improvement of her well-being by enabling the patient to interact and integrate
      socially within her environment after mobilising the corresponding social and
      family resources.Involvement in clinical practice is important in the prevention
      of diabetes mellitus and diabetic foot complications. Difficult and complex
      situations are sometimes beyond the ability of the community nurse. It can be
      beneficial to take advantage of the clinical support offered by the case
      management model and the integrated approach of a multidisciplinary team.

PMID- 21872520
TI  - [Emergency cervical cerclage during mid-trimester of pregnancy: Experience of
      Clermont-Ferrand].
AB  - OBJECTIVES: The objective of this study was to identify factors associated with
      favourable perinatal outcome after emergency cervical cerclage during mid
      trimester of pregnancy. PATIENTS AND METHODS: This is a retrospective study of
      all cases who underwent emergency cervical cerclage between 16 to 28 weeks of
      gestation (WG) over a period of 16 years in a University Hospital. RESULTS: Among
      the 32 cases, the postnatal survival rate (day 28) was 80%. Delivery occurred at
      a mean gestational age of 33.1 WG [18-41.3 WG] and after 37 WG in 39% of cases.
      The perinatal outcome was improved by absence of bleeding (P=0.01), unripened
      cervix (P=0.02), cervical dilatation below 2 cm (P=0.002), no protruding
      membranes (P=0.02) and more advanced gestational age at the procedure (P=0.005).
      When no uterine contraction and no maternal blood inflammation were observed at
      admission, an expectancy of 48 hours before the procedure did not improve
      significantly perinatal outcome (gestational age at birth and survival rate
      [P=0.1 and P=0.3 respectively]). DISCUSSION AND CONCLUSION: Perinatal outcome
      after emergency cerclage depends on cervical status and gestational age at
      procedure. It is not influenced by an expectancy of 48 hours before intervention
      for patients with no uterine contraction and no maternal blood inflammation at
      admission.

PMID- 21872521
TI  - The effect of cup inclination and wear on the contact mechanics and cement
      fixation for ultra high molecular weight polyethylene total hip replacements.
AB  - The present study aimed to investigate individual and combined influences of the
      cup inclination and wear on the contact mechanics and fixation of a Charnley hip
      replacement using finite element method. The effects of cup inclination and
      penetration on the contact mechanics of articulating bearings as well as the
      stress within the cement and at the bone-cement interface were examined. The
      maximum contact pressure and the von Mises stress on the cup were reduced by ~30%
      and ~20% respectively when even a small penetration occurred. However, no large
      differences were found between different cup penetration depths with regards to
      either the contact pressure or the von Mises stress. The von Mises stress at the
      bone-cement interface was predicted almost unaltered with an increased cup
      inclination angle to 55 degrees  for a cup penetration to 4mm. These predictions
      suggest that the contact mechanics and the cement stress are insensitive to the
      cup inclination and wear under these normal conditions investigated, therefore
      explaining the robustness of the Charnley hip implant. An increase in the cup
      inclination angle to 65 degrees , coupled with a maximum penetration of 4mm,
      resulted in a large increase in the maximum von Mises stress at the bone-cement
      interface.

PMID- 21872522
TI  - The utility of laser-generated visual-cueing in parkinsonian patients with gait
      freezing.

PMID- 21872523
TI  - Assessing the utility of Freezing of Gait Questionnaires in Parkinson's Disease.
AB  - There are currently two validated questionnaires, the Freezing of Gait
      Questionnaire and the New Freezing of Gait Questionnaire, that are intended to
      assess the degree of freezing of gait in patients with Parkinson's disease.
      However, to date no study has attempted to determine whether ratings on these
      questionnaires accurately reflect the severity (frequency and duration) of actual
      freezing episodes experienced by patients. We studied twenty-four patients with
      Parkinson's disease who self-reported significant freezing while in their
      practically-defined 'off' state. Prior to clinical assessment they completed both
      freezing of gait questionnaires before being video-recorded while performing a
      series of timed up-and-go tasks, which incorporated turning, rotating and passing
      through narrow gaps. The rating of video recordings by two independent observers
      identified a total of 530 freezing events. The frequency and duration of freezing
      episodes for each patient were calculated and correlated with questionnaire
      ratings. Scores on either questionnaire did not correlate with either the
      frequency or duration of freezing episodes experienced by patients during
      objective assessment. These results suggest the need to re-evaluate the utility
      of questionnaires in the assessment of freezing of gait. Furthermore, these
      results highlight the need for accurate objective methods of identifying freezing
      events when assessing future clinical interventions aimed at reducing this
      potentially disabling symptom of Parkinson's disease.

PMID- 21872524
TI  - Evaluation of outcome measures for use in clinical practice for adults with
      musculoskeletal conditions of the knee: a systematic review.
AB  - BACKGROUND: This systematic review reported on the clinimetric properties of
      outcome measures for use in clinical practice for adults with musculoskeletal
      conditions of the knee. METHODS: A systematic search was performed in Medline,
      EMBASE, Cinahl and AMED to identify studies examining the clinimetric properties
      of outcome measures for adults undergoing conservative treatment of ligament
      injuries, meniscal lesions, patellofemoral pain and osteoarthritis of the knee.
      Outcomes measures taking less than 20 min to administer and requiring minimal
      equipment and space were included. Pairs of authors used a checklist to record
      the characteristics of the outcome measures, their reported clinimetric
      properties and the demographics of the study populations. The OMERACT filters of
      'truth' and 'discrimination' were applied to the data for each outcome measure by
      an expert panel. RESULTS: Forty-seven studies were included evaluating 37 outcome
      measures. Ten outcome measures had adequate supporting evidence for 'truth' and
      'discrimination': AAOS, AKPS, goniometer measurement, IKDC, KOOS, LEFS, Lysholm,
      Tegner, WOMAC and WOMET. However none of the outcome measures had been
      comprehensively tested across all clinimetric properties. CONCLUSION: Despite the
      widespread use of some outcome measures in clinical practice and primary
      research, data on the clinimetric properties were available for only 37 and of
      these only 10 had adequate supporting evidence for use in this population.
      However, before a core set of outcome measures can be recommended use in clinical
      practice, for adults with musculoskeletal conditions of the knee, consensus
      should be obtained on 'feasibility' in terms of burden on the clinician and the
      participant.

PMID- 21872525
TI  - The breach rhythm.
AB  - Electroencephalography (EEG) recordings obtained after craniotomy are difficult
      to interpret because of the presence of a breach rhythm (BR) consisting of
      unfiltered high-voltage physiological waveforms, sometimes with a spiky and
      irregular morphology, that can mimic interictal epileptiform abnormalities and
      may therefore lead to misinterpretations. In this article, we review EEG features
      of BR and give some technical tips to properly interpret BR and to make a correct
      differential diagnosis with epileptiform abnormalities. As BR itself has no
      relationship to epilepsy, it is very important to adopt a "conservative" reading,
      having a high threshold to call epileptiform abnormalities.

PMID- 21872526
TI  - Characterization of early partial seizure onset: frequency, complexity and
      entropy.
AB  - OBJECTIVE: A clear classification of partial seizures onset features is not yet
      established. Complexity and entropy have been very widely used to describe
      dynamical systems, but a systematic evaluation of these measures to characterize
      partial seizures has never been performed. METHODS: Eighteen different measures
      including power in frequency bands up to 300 Hz, Gabor atom density (GAD),
      Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample
      entropy, and permutation entropy, were selected to test sensitivity to partial
      seizure onset. Intracranial recordings from 45 patients with mesial temporal,
      neocortical temporal and neocortical extratemporal seizure foci were included
      (331 partial seizures). RESULTS: GAD, Lempel-Ziv complexity, HFD, high frequency
      activity, and sample entropy were the most reliable measures to assess early
      seizure onset. CONCLUSIONS: Increases in complexity and occurrence of high
      frequency components appear to be commonly associated with early stages of
      partial seizure evolution from all regions. The type of measure (frequency-based,
      complexity or entropy) does not predict the efficiency of the method to detect
      seizure onset. SIGNIFICANCE: Differences between measures such as GAD and HFD
      highlight the multimodal nature of partial seizure onsets. Improved methods for
      early seizure detection may be achieved from a better understanding of these
      underlying dynamics.

PMID- 21872527
TI  - Evolution in the techniques and outcomes of aortic arch surgery: a 22 year single
      centre experience.
AB  - BACKGROUND: Aortic arch replacement is a complicated and high risk procedure.
      There have been many advances over recent years. We review the changes in our
      unit's techniques and outcomes over the past 22 years. METHODS: Data were
      collated from databases and medical records for all patients who underwent aortic
      arch replacement surgery from January 1989 to December 2010. The patients were
      divided into two groups - Group A (1989-2005) and Group B (2006-2010). Data were
      analysed to compare early and late series patients' outcomes. Logistic regression
      was used to identify variables that predicted mortality. RESULTS: Seventy-five
      eligible patients (56 males; mean age: 57.5 years; Group A: 40, Group B 35) were
      identified. There were great changes in the technique and the methods of cerebral
      protection. The overall mortality rate was 30.7% - Group A: 50% and Group B: 8.6%
      (p<0.001). Overall permanent neurological dysfunction was 23.7% - Group A: 40%
      and Group B: 11.8% (p=0.012). Cardiovascular disease and circulatory arrest time
      were significant predictors of mortality. CONCLUSIONS: Increased experience and
      volume and advances in techniques over 22 years have resulted in major
      improvements in outcomes for patients having aortic arch replacement, allowing
      the procedure to be performed with greatly improved outcomes.

PMID- 21872528
TI  - The journey from the old to the new AMH assay: how to avoid getting lost in the
      values.
AB  - Anti-Mullerian hormone (AMH) is set to dominate reproductive endocrinology
      because of its unique relationship with the ovarian reserve. To date half of the
      published articles have used the Diagnostic Systems Lab (DSL) assay and the other
      half the Immunotech (IOT) assay. Unfortunately, these assays utilize two
      different primary antibodies against AMH and different standards, and
      consequently the crude values reported can differ substantially, with the IOT
      assay giving values for AMH that are higher than those obtained with the DSL
      assay. With the recent consolidation of these two companies by Beckman Coulter,
      and their sole ownership of the patent to measure mammalian AMH, there is finally
      a single commercially available assay - the AMH Gen II assay, which will fully
      replace the DSL and IOT assays. The aim of this article is to briefly focus on
      the different assays for AMH evaluation in order to give readers hopefully
      helpful suggestions for a correct interpretation of the AMH measurement. A brief
      overview on the development and performance characteristics of the new assay, how
      it relates to previous values and previously developed nomograms and where the
      future lies for AMH is also provided.

PMID- 21872529
TI  - Change in transfusion practice in massively bleeding patients.
AB  - This retrospective study evaluates changes in transfusion practice and modified
      blood product utilisation that occurred over the course of eleven years in
      patients receiving massive transfusion. The mean number of fresh frozen plasma
      units transfused increased from 9.0 +/- 7.9 in 1998 to 11.3 +/- 6.7 in 2008
      (p=0.03). The mean number of platelet units increased from 1.9 +/- 1.3 in 1998 to
      2.6 +/- 1.7 in 2008 (p=0.02). The proportion of cryoprecipitate increased from
      0.03 +/- 0.19 in 1998 to 1.3 +/- 1.6 in 2008 (p=0.001). Along with these changes
      was a trend toward decreased mortality (p=0.05).

PMID- 21872530
TI  - Therapeutic plasma exchange in amitriptyline intoxication: case report and review
      of the literature.
AB  - Severe amitriptyline poisoning results in cardiac and neurological toxicity and
      continues to be a leading cause of significant morbidity and mortality both in
      children and adults. We present a case of severe amitriptyline poisoning
      successfully treated with plasma exchange. Due to high plasma protein binding
      property of amitriptyline, plasma exchange therapy should be considered in cases
      of severe amitriptyline intoxication as a life saving therapeutic modality.

PMID- 21872531
TI  - HIV-1-resistance-associated mutations after failure of first-line antiretroviral
      treatment among children in resource-poor regions: a systematic review.
AB  - HIV-positive children are at high risk of drug resistance, which is of particular
      concern in settings where antiretroviral options are limited. In this Review we
      explore resistance rates and patterns among children in developing countries in
      whom antiretroviral treatment has failed. We did a systematic search of online
      databases and conference abstracts and included studies reporting HIV-1 drug
      resistance after failure of first-line paediatric regimens in children (<18
      years) in resource-poor regions (Latin America, Africa, and Asia). We retrieved
      1312 citations, of which 30 studies reporting outcomes in 3241 children were
      eligible. Viruses with resistance-associated mutations were isolated from 90%
      (95% CI 88-93%) of children. The prevalence of mutations associated with
      nucleoside reverse transcriptase inhibitors was 80%, with non-nucleoside reverse
      transcriptase inhibitors was 88%, and with protease inhibitors was 54%. Methods
      to prevent treatment failure, including adequate paediatric formulations and
      affordable salvage treatment options are urgently needed.

PMID- 21872533
TI  - Is sleep-related consolidation impaired in focal idiopathic epilepsies of
      childhood? A pilot study.
AB  - We investigated sleep-related declarative memory consolidation in four children
      with focal idiopathic epilepsy. In a population of healthy control children,
      recall of learned pairs of words was increased after a night of sleep, but not
      after a daytime wakefulness period. In children with epilepsy (1 case of benign
      epilepsy with centro-temporal spikes, 1 case of benign childhood epilepsy with
      occipital paroxysms, and 2 cases of epileptic encephalopathy (EE) with continuous
      spike and waves during slow-wave sleep, CSWS), recall performance significantly
      decreased overnight, suggesting impairment in sleep-related declarative memory
      consolidation. Hydrocortisone treatment in one patient with EE with CSWS resulted
      in normalization of the sleep EEG together with normalization of overnight memory
      performance, which was not the case in the other EE/CSWS patient whose sleep EEG
      was only partially improved. These preliminary results suggest that interictal
      epileptiform discharges in idiopathic focal epilepsies may disrupt the brain
      processes underlying sleep-related memory consolidation.

PMID- 21872532
TI  - IL-17 induces apoptosis of vascular endothelial cells: a potential mechanism for
      human acute coronary syndrome.
AB  - Th17 cells producing IL-17 are involved in the pathogenesis of atherosclerosis,
      but the underlying mechanisms remain unclear. In this study, we investigated the
      effects of IL-17 on human vascular endothelial cells and showed that IL-17
      induced cell death of the vascular endothelial cells, which played a pivotal role
      in plaque destabilization triggering acute coronary syndrome (ACS). We showed
      that circulating Th17 cells and IL-17 increased in patients with ACS compared to
      the patients with stable angina or health individuals; the plasma levels of IL-6
      increased but TGF-beta decreased in ACS patients, exhibiting a positive and
      negative correlation with that of IL-17, respectively. Importantly, we uncovered
      that IL-17 promoted the production of von Willebrand factor by endothelial cells
      and induced endothelial apoptosis by activating caspase-3, caspase-9 and up
      regulating the ratio of Bax/Bcl-2, indicating the function of IL-17 in vascular
      endothelial damage as a potential mechanism for the pathogenesis of human ACS.

PMID- 21872534
TI  - Clinical and economic impact of vagus nerve stimulation therapy in patients with
      drug-resistant epilepsy.
AB  - We evaluated long-term medical and economic benefits of vagus nerve stimulation
      (VNS) therapy in drug-resistant epilepsy. A pre-post analysis was conducted using
      multistate Medicaid data (January 1997-June 2009). One thousand six hundred fifty
      five patients with one or more neurologist visits with epilepsy diagnoses (ICD-9
      345.xx, 780.3, or 780.39), one or more procedures for vagus nerve stimulator
      implantation, one or more antiepileptic drugs (AEDs), and 6 or more months of
      continuous Medicaid enrollment pre- and post-VNS were selected. The pre-VNS
      period was 6 months. The post-VNS period extended from implantation to device
      removal, death, Medicaid disenrollment, or study end (up to 3 years). Incidence
      rate ratios (IRRs) and cost differences ($2009) were estimated. Mean age was 29.4
      years. Hospitalizations decreased post-VNS compared with pre-VNS (adjusted
      IRR=0.59, P<0.001). Grand mal status events decreased post-VNS compared with pre
      VNS (adjusted IRR=0.79, P<0.001). Average total health care costs were lower post
      VNS than pre-VNS ($18,550 vs $19,945 quarterly, P<0.001). VNS is associated with
      decreased resource utilization and epilepsy-related clinical events and net cost
      savings after 1.5 years.

PMID- 21872535
TI  - Nursing aide reports of combative behavior by residents with dementia: results
      from a detailed prospective incident diary.
AB  - OBJECTIVES: This study examined nursing aides' (NAs) perspectives of specific
      incidents of combative behavior from nursing home residents with dementia,
      particularly their attributions for the behaviors. DESIGN: This research is part
      of a larger mixed-method study exploring combative behavior as experienced by
      NAs. The data for this component were collected using a cross-sectional survey
      design. NAs used a prospective event-reporting log or "diary" to record
      consecutive incidents of combative resident behaviors. SETTING: Eleven rural
      nursing homes located in a mid-Western Canadian province. PARTICIPANTS: Eighty
      three full-time, part-time, and casual NAs. MEASUREMENTS: NAs used the diary
      instrument to document details of each incident of combative behavior over a 144
      hour period. Findings from the diaries were explored in subsequent focus groups
      (reported elsewhere). RESULTS: The 83 NAs reported 409 incidents linked to
      residents with dementia, with a range of 1 to 28 incidents per aide. The
      frequency of incidents in the preceding month was reported as follows: none
      (11.1%), 1-5 times (58.7%), 6-10 times (11.1%), more than 10 times (19.0%). Most
      incidents occurred in residents' rooms (65%) during personal care, with the most
      frequent behaviors reported as slapping, squeezing, punching or hitting, and
      shoving. The main perceived causes of the behavior were cognitive impairment and
      residents not wanting care. NAs reported they could control or modify the cause
      in only 3% of incidents, and they were not optimistic about preventing future
      combative behaviors. They continued to provide care in 89% of incidents.
      CONCLUSION: In the diaries, NAs identified resident-related factors (cognitive
      impairment and not wanting care) as the main causes of combative behavior, and
      they reported having no control over these factors. In the focus groups conducted
      to explore diary findings, NAs reported system-level factors, also beyond their
      control, which affected their practices and increased their risk of exposure to
      combative behavior. Taken together, the results of this research program suggest
      a need for a broad multifaceted strategy aimed at addressing the modifiable risk
      factors, which includes recognizing NAs as equal partners in a team process
      backed by strong organizational support and commitment.

PMID- 21872536
TI  - Complications and mortality after percutaneous endoscopic gastrostomy in
      geriatrics: a prospective multicenter observational trial.
AB  - BACKGROUND: Generally, the high short-term mortality after percutaneous
      endoscopic gastrostomy (PEG) in geriatric patients is attributed to the severity
      of their underlying diseases. However, the procedure-related mortality in this
      group is unknown. METHODS: This prospective multicenter observational study
      gathered information about 197 geriatric patients treated with PEG insertion,
      including the indication for PEG insertion and the prevalence of postprocedure
      complications and analyzed how these factors related to mortality. RESULTS:
      Dysphagia (64%) and insufficient food intake (76%) were the most frequent
      indications for PEG insertion. Severe complications after PEG insertion occurred
      in 9.6% of patients. Mortality was 9.6% in hospital, as well as 18.4% at 1 month.
      Six months after PEG placement, with 81 patients lost to follow-up, mortality was
      51.9%. Hospital mortality was significantly higher in patients with severe
      complications caused by PEG insertion (47.4% vs 5.6%; P < .001). A regression
      analysis that corrected for confounding factors revealed that severe
      complications in general (HR 6.9; 95% CI: 2.6-18.1; P < .001), peritonitis (HR
      33.1; 95% CI: 3.7-293.2; P = .002), and severe wound infections (HR 6.9; 95% CI:
      1.9-24.9; P = .003) were each independently associated with hospital mortality.
      Considering the prevalence of procedure-related complications and their
      association with early mortality after PEG insertion, the procedure-related
      mortality rate in geriatric patients was at least 2% in this study. CONCLUSION:
      Although the prevalence of complications after PEG in this study of multimorbid
      geriatric patients is within the expected range, the procedure-related mortality
      is higher than expected.

PMID- 21872538
TI  - Quantification of the antifungal lipopeptide iturin A by high performance liquid
      chromatography coupled with aqueous two-phase extraction.
AB  - Iturin A, a powerful antifungal surfactant, is a kind of bacterial lipopeptide
      produced by Bacillus strains. This study addresses the use of an aqueous two
      phase system (ATPS) using ethanol/ammonium sulfate to extract iturin A from
      Bacillus amyloliquefaciens NJN-6 fermentation broth and the quantification of
      iturin A by HPLC. Baseline separation of iturin A homologues was performed using
      an RP-C(18) column with a mixture of water and acetonitrile. The results showed
      that the correlation coefficient between integral area and concentration was
      0.9961 within the range of 20-140 mg/l. The RSD of the retention time and the
      peak area were 1.29% and 1.45%, respectively. The effects of some operating
      parameters in ATPS, e.g., pH, temperature and centrifugation time, were also
      studied. This method can be successfully used for the rapid quantification of
      iturin A.

PMID- 21872537
TI  - What are the barriers to performing nonpharmacological interventions for
      behavioral symptoms in the nursing home?
AB  - OBJECTIVE: Behavioral symptoms are common in persons with dementia, and
      nonpharmacological interventions are recommended as the first line of therapy. We
      describe barriers to conducting nonpharmacological interventions for behavioral
      symptoms. DESIGN: A descriptive study of barriers to intervention delivery in a
      controlled trial. SETTINGS: The study was conducted in six nursing homes in
      Maryland. PARTICIPANTS: Participants were 89 agitated nursing home residents with
      dementia. INTERVENTION: Personalized interventions were developed using the
      Treatment Routes for Exploring Agitation decision tree protocol. Trained research
      assistants prepared and delivered the interventions. Feasibility of the
      interventions was determined. MEASUREMENTS: Barriers to Intervention Delivery
      Assessment, activities of daily living, cognitive functioning, depressed affect,
      pain, observed agitation, and observed affect. RESULTS: Barriers were observed
      for the categories of resident barriers (specifically, unwillingness to
      participate; resident attributes, such as unresponsive), barriers related to
      resident unavailability (resident asleep or eating), and external barriers (staff
      related barriers, family-related barriers, environmental barriers, and system
      process variables). Interventions pertaining to food/drink and to 1-on-1
      socializing were found to have the fewest barriers, whereas higher numbers of
      barriers occurred with puzzles/board games and arts and crafts activities.
      Moreover, when successful interventions were presented to participants after the
      feasibility period, we noted fewer barriers, presumably because barrier
      identification had been used to better tailor interventions to each participant
      and to the environment. CONCLUSION: Knowledge of barriers provides a tool by
      which to tailor interventions so as to anticipate or circumvent barriers, thereby
      maximizing intervention delivery.

PMID- 21872539
TI  - One single HPLC-PDA/(-)ESI-MS/MS analysis to simultaneously determine 30
      components of the aqueous extract of Rabdosia rubescens.
AB  - In China the leaves of Rabdosia rubescens have been cooked in water and widely
      drank to treat inflammatory and pain related diseases. To explore the components
      that were possibly absorbed by people the aqueous extract of the leaves was
      prepared, and one single HPLC-PDA/(-)ESI-MS/MS analysis was developed to
      simultaneously determine the components. Using the HPLC-PDA analysis 39 peaks
      were found in the aqueous extract, while using the (-)ESI-MS/MS analysis we were
      able to identify 30 peaks represented components, including 5 nucleic acids, 21
      phenolic acids and 4 diterpenoids. On mouse models the in vivo anti-inflammation
      and analgesic actions demonstrate that 0.32 g/kg of the aqueous extract of the
      leaves of Rabdosia rubescens can effectively inhibit the inflammation-induced
      chronic pain.

PMID- 21872540
TI  - Affinity adsorption of lysozyme on a macroligand prepared with Cibacron Blue 3GA
      attached to yeast cells.
AB  - The objective of this study was the development of affinity adsorbent particles
      with the appropriate characteristics to be applied in protein purification using
      the affinity ultrafiltration method. To prepare affinity macroligands Cibacron
      Blue 3GA, as a ligand molecule, was immobilized by covalent bonding onto yeast
      cell walls, the support material or matrix. The maximum attachment of the ligand
      to the matrix was 212 MUmol/g (ligand dry weight/yeast dry weight). Lysozyme was
      selected as the protein model for the adsorption studies. Its adsorption onto the
      matrix without ligand and matrix with attached ligand were investigated batch
      wise. The adsorption equilibrium isotherms appeared to follow a typical Langmuir
      isotherm. The maximum adsorption capacity (q(m)) of the Cell-Cibacron macroligand
      for lysozyme was 110 mg/ml of wet macroligand. The adsorbent was also employed
      for the separation of lysozyme from hen egg white. High purity lysozyme was
      obtained.

PMID- 21872541
TI  - Development and validation of highly sensitive method for determination of
      misoprostol free acid in human plasma by liquid chromatography-electrospray
      ionization tandem mass spectrometry: application to a clinical pharmacokinetic
      study.
AB  - A highly sensitive, selective and evaporation free SPE extraction, ESI-LC-MS/MS
      method has been developed for estimation of misoprostol free acid in human plasma
      using misoprostol acid-d(5) as an internal standard (IS). The analyte was
      separated using isocratic mobile phase on reverse phase column and analyzed by
      MS/MS in the multiple reaction monitoring mode using the respective [M-H] anions,
      m/z 367-249 for misoprostol acid and m/z 372-249 for the IS. The total run time
      was 5.0 min and the elution of misoprostol acid and misoprostol acid-d(5) (IS)
      occurred at 3.6 min. The developed method was validated in human plasma with a
      lower limit of quantification of 2.5 pg/mL. A linear response function was
      established for the range of concentrations 2.5-1200 pg/mL (r>0.998) for
      misoprostol acid in human plasma. The intra and inter-day precision values for
      misoprostol acid met the acceptance as per FDA guidelines. Misoprostol acid was
      stable in the battery of stability studies viz., bench-top, auto-sampler and
      freeze/thaw cycles. The developed assay method was applied to an oral
      pharmacokinetic study in humans.

PMID- 21872542
TI  - Management of umbilical hernia complicated with liver cirrhosis: an advocate of
      early and elective herniorrhaphy.
AB  - BACKGROUND: Patients with umbilical hernias complicated by liver cirrhosis have
      an increased likelihood of complications following herniorrhaphy. The aim of this
      study was to investigate the clinical outcomes in patients with umbilical hernias
      complicated by liver cirrhosis. METHODS: Between 2001 and 2010, 44 patients were
      enrolled in this study. The comparison between non-operative and operative group
      was performed. Patients who underwent emergency versus elective surgery were also
      compared. RESULTS: Of the 44 patients, there were 33 men and 11 women. Thirty-one
      patients (70.5%) underwent surgery and 13 patients (29.5%) were treated
      conservatively. Overall morbidity and mortality rates following herniorrhaphy
      were 42% and 6.5%. The mean albumin level was significantly lower and total
      bilirubin, creatinine and mean model of end-stage liver disease score were
      significantly higher in non-operative group than in operative group. Combined
      resection was performed more frequently in the emergency group than in elective
      group. A significantly higher proportion of patients in emergency operation group
      had postoperative complications (P=0.01), especially ascites (P=0.02). The
      operative time and postoperative hospital stay were significantly shorter in the
      elective operation group than in emergency operation group. CONCLUSIONS: Early,
      elective repair of umbilical hernias in cirrhotic patients should be advocated
      considering the hepatic reserve and patient's condition. Ascites control is the
      mainstay of post-operative management.

PMID- 21872543
TI  - Developmental haemostasis: secondary haemostasis.
AB  - The haemostatic system is a complex interaction between the vasculature, cellular
      components and plasma proteins that interact to maintain haemostasis in the
      healthy body. The haemostatic system can be further defined as primary, secondary
      and tertiary haemostasis to better define the interdependent mechanisms that
      combine to maintain haemostasis. The term 'developmental haemostasis' was first
      introduced by Maureen Andrews in the 1980s to describe the age-related
      physiological changes of the coagulation system as it develops progressively over
      time from fetal, neonatal, paediatric to adult and geriatric systems. This paper
      will focus on developmental changes in secondary haemostasis, that is, the plasma
      protein changes that occur with age, particularly during the fetal and neonatal
      period, when the changes are most marked compared to the adult system.

PMID- 21872544
TI  - Cicatricial ectropion: a complication of topical 5-fluorouracil.
AB  - Topical 5-fluorouracil (5-FU) is a simple chemotherapeutic treatment that can be
      used by the plastic surgeon for indicated skin lesions. We present a case of
      transient, cicatricial ectropion developing secondarily to topical treatment with
      5-FU, and propose an algorithm for the management of this significant
      complication.

PMID- 21872545
TI  - Dynamic infrared thermography for the preoperative planning of microsurgical
      breast reconstruction: a comparison with CTA.

PMID- 21872546
TI  - A multidisciplinary protocol for face transplantation at Brigham and Women's
      Hospital.
AB  - Face transplantation introduces an unprecedented potential to restore form and
      function in patients with severe facial disfigurement. A successful face
      transplantation programme requires a sound research protocol, a solid
      infrastructure, expert personnel and adequate funding. There are only a few
      active face transplant programmes in the world and interest in the development of
      new such programmes continues to grow. After 2 years of working on the
      development of the face transplant programme, in 2009 the team at Brigham and
      Women's Hospital (BWH) performed the 2nd face transplant in the United States.
      Since then, the team has continued to evaluate several possible face transplant
      candidates and performed three additional facial transplants. These experiences
      have helped refine a highly effective multidisciplinary protocol that carries a
      patient through recruitment, informed consent, screening, preoperative planning,
      face transplantation surgery and postoperative long-term follow-up. The members
      of the BWH face transplantation team responsible for carrying out this protocol
      include a team leader, a programme manager/coordinator, clinical and
      rehabilitation specialists, social workers, bioethicists, nurses and
      administrative staff. The roles of each team member during the various stages of
      the face transplant process are presented here. Additional insight into the
      interaction between the face transplant team, the Institutional Review Board and
      the regional Organ Procurement Organization is given. The BWH team's experience
      has shown that true collaboration, creativity and a unique approach to each
      candidate translate into the optimal care of the face transplant patient both
      before and after surgery.

PMID- 21872547
TI  - Total knee replacement following intra-articular malunion.
AB  - INTRODUCTION: There is a lack of data on the management of osteoarthritis of the
      knee associated with intra-articular malunion. The present study sought to
      analyze and report results of total knee replacement (TKR) in this indication,
      including complications and technical specificities. HYPOTHESIS: TKR for
      osteoarthritis of the knee associated with intra-articular malunion entails an
      elevated risk of complication, with impaired functional results. OBJECTIVES: To
      test this hypothesis in a retrospective series of 74 cases of osteoarthritis of
      the knee associated with intra-articular malunion. PATIENTS AND METHODS: A
      multicenter retrospective series collated the records of 74 patients (mean age,
      63 +/- 14 years) who underwent TKR for post-traumatic osteoarthritis of the knee
      associated with intra-articular malunion between 2000 and 2008. Mean trauma-to
      TKR interval was 21.8 +/- 19 years (range 1 to 56 years). Patients were assessed
      clinically and radiologically at last follow-up, using the Knee Society score as
      modified by the Western France Orthopedic Society (Societe orthopedique de
      l'Ouest). RESULTS: At a mean overall follow-up of 4 +/- 3 years (range 1 to 9
      years), mean knee score improved from 25 +/- 12 to 85 +/- 7 (P<0.001) and mean
      functional score from 52 +/- 13 to 66 +/- 10 (P=0.004). Mean flexion gain was 6
      degrees : mean preoperative flexion, 104 degrees  +/- 28 degrees  (10 degrees  to
      150 degrees ), vs. 110 degrees  +/- 19 degrees  (20 degrees  to 130 degrees ) at
      follow-up. Nineteen patients (26%) had complications, 13 of which were severe and
      liable to affect the functional result: three extensor system avulsions, four
      infections, five cases of stiffness and one of instability. DISCUSSION AND
      CONCLUSIONS: The present results highlight an elevated rate of complications,
      with poorer clinical results than those found with osteoarthritis of the knee
      secondary to constitutional deformity. The initial trauma, with associated
      hemarthrosis, and sometimes iterative surgery to reduce and fix the initial
      fracture, induce fibrosis and synovial attachments, leading to stiffness and
      hindering exposure. The patient should be informed, and warned that postoperative
      flexion amplitude may be improved but is bound to remain limited, especially in
      case of initial stiffness. LEVEL OF EVIDENCE: Level IV: non-comparative
      retrospective study.

PMID- 21872548
TI  - Management of supra-mesocolic peritonitis using the Levy helicoid drain
      (Helisonde(r)).
AB  - INTRODUCTION: Postoperative peritonitis arising in the upper abdomen requiring
      reoperative surgery has a mortality rate of up to 50%. One therapeutic modality
      for these patients is the use of the Helisonde((r)) drain, designed by Levy, the
      Levy Helical Drain (LHD), but it has not seen widespread use. In this paper, we
      describe our experience in managing supramesocolic peritonitis with this drain at
      the University Surgical Center at Amiens and we analyze our results. PATIENTS AND
      METHODS: Between 2005 and 2010, we cared for 190 patients with supramesocolic
      peritonitis in our unit. Of these, 22 patients with gastric or duodenal fistula
      underwent transorificial intubation with the LHD. There were 12 men and 10 women
      with a mean age of 66 years. At surgery, the helical drain was screwed into the
      fistular orifice, two more flat drains were left adjacent to the fistula, and a
      jejunal feeding tube was placed. The mean interval between the initial surgery
      and the drainage procedure was 16.1 +/- 14 days. RESULTS: The mean APACHE II
      score was 20 (10-28). The Mannheim score averaged 28 (19-34). The LHD was
      completely removed at a mean interval of 35.5 +/- 11 days. Six patients (27%)
      died postoperatively. Postoperative complications included intraperitoneal
      abscess (n = 3), pneumonia (n=1), and evisceration (n = 2). Two patients required
      reoperation. The average hospital stay was 70.7 days. Four patients had a
      persistent chronic fistula. CONCLUSION: The LHD is a useful technical device in
      the treatment of supramesocolic peritonitis. Its management requires close
      oversight.

PMID- 21872549
TI  - Mesenteric myofibroblastic tumor: NSAID therapy after incomplete resection.
AB  - Myofibroblastic tumors are inflammatory tumors that arise in viscera and soft
      tissue; their etiopathology is poorly understood. They are capable of
      infiltration of adjacent organs, local recurrence after surgical resection, and
      even of distant metastasis. These characteristics result in persistent debate as
      to the nature of these lesions - whether they are inflammatory or neoplastic,
      benign or malignant lesions? Diagnosis is almost always made based on
      histopathological findings. Traditional management is complete surgical excision,
      but this may be difficult or impossible when the lesion develops in proximity to
      vital structures. We report the case of a 59-year-old man who was treated in our
      institution for mesenteric myofibroblastic tumor. Complete resection was not
      possible due to local infiltration of the mesentery. Recurrence was noted 3
      months after surgery; treatment with steroidal and then non-steroidal anti
      inflammatory medications (NSAIDs) resulted in clinical and radiologic regression
      of the tumor.

PMID- 21872550
TI  - Racial and ethnic disparities in employment outcomes for persons with traumatic
      brain injury: a longitudinal investigation 1-5 years after injury.
AB  - OBJECTIVE: To determine whether differences exist in employment rates between
      whites, blacks, and Hispanics with traumatic brain injury (TBI) at 1, 2, or 5
      years after injury; to determine whether changes occur in postinjury employment
      rates over time for whites, blacks, and Hispanics; and to determine whether
      changes in postinjury employment rates over time are different for whites,
      blacks, and Hispanics. SETTING: Sixteen TBI Model System centers. PATIENTS OR
      OTHER PARTICIPANTS: Persons (3,940) with moderate-to-severe TBI who self-reported
      as white, black, or Hispanic. MAIN OUTCOME MEASUREMENTS: Employment status
      dichotomized as competitively employed versus not competitively employed.
      RESULTS: The odds of competitive employment were significantly greater for whites
      versus blacks at 1, 2, and 5 years after injury and were greater for whites
      versus Hispanics at 1 and 2 years after injury; whites and Hispanics did not
      differ significantly at 5 years after injury; and blacks and Hispanics were not
      significantly different at 1, 2, or 5 years after injury. The odds of employment
      increased significantly from 1-2, 2-5, and 1-5 years after injury for whites and
      Hispanics, whereas the odds of employment increased from 2-5 and 1-5 years after
      injury for blacks, with no significant difference between 1 and 2 years after
      injury for blacks. No evidence was found that the changes in employment rates
      over time were significantly different among the race and/or ethnicity groups.
      CONCLUSION: Future researchers should seek to identify causative factors for
      employment disparities, and rehabilitation professionals should work to mitigate
      inequalities in employment among racial and ethnic groups with TBI.

PMID- 21872551
TI  - Treatment of chronic tendinopathy with ultrasound-guided needle tenotomy and
      platelet-rich plasma injection.
AB  - OBJECTIVE: To determine whether ultrasound (US)-guided percutaneous needle
      tenotomy followed by a platelet-rich plasma (PRP) injection would result in pain
      reduction, functional improvement, or structural alterations in patients with
      chronic, recalcitrant tendinopathy. DESIGN: Part A was a retrospective
      observational study. Part B was a prospective observational study. SETTING:
      Outpatient academic sports medicine center. PARTICIPANTS: Patients were required
      to have chronic (>3 months), recalcitrant tendinopathy treated with US-guided
      percutaneous tenotomy and PRP injection between January 2007 and October 2009.
      Fifty-one subjects met the inclusion criteria. Forty-one (80%) participated in
      part A of the study, whereas 34 subjects (67%) participated in part B. METHODS:
      In part A, subjects completed a survey obtaining anthropomorphic, demographic,
      pain, and functional data. Subjects' platelet, hemoglobin, and white blood cell
      concentrations from their whole-blood and PRP samples were also obtained. In part
      B, subjects returned to the clinic after US-guided percutaneous needle tenotomy
      and PRP injection for a diagnostic US, which was compared with their preprocedure
      diagnostic US. MAIN OUTCOME MEASURES: The main outcome measures included changes
      in pain, function, and tendon characteristics. RESULTS: The tendinopathy location
      was in the upper extremity in 10 subjects (24.4%), was in the lower extremity in
      31 subjects (75.6%), and had been present for a mean of 40 months. The mean
      postprocedure follow-up was 14 months, and the maximum benefits occurred 4 months
      postprocedure. There were mean functional and worst-pain improvements of 68% and
      58%, respectively. Eighty-three percent of subjects were satisfied with their
      outcomes and would recommend the procedure to a friend. Although no tendons
      demonstrated a normal sonographic appearance after the procedure, 84% of subjects
      had an improvement in echotexture, 64% had a resolution of intratendinous
      calcifications, and 82% had a decrease in intratendinous neovascularity. None of
      the variables analyzed in this study demonstrated a significant correlation with
      pain or functional outcome measures. CONCLUSIONS: In this case series, we found
      US-guided percutaneous needle tenotomy followed by PRP injection to be a safe and
      effective treatment for chronic, recalcitrant tendinopathy, and this treatment
      was associated with sonographically apparent improvements in tendon morphology.
      However, because of the intrinsic limitations of the study design and the
      heterogeneity of treated tendons, further research is required to corroborate our
      findings.

PMID- 21872552
TI  - Study of serum ghrelin changes and its correlation with malnutrition in liver
      cirrhosis in Egypt.
AB  - Egypt has the highest prevalence of hepatitis C virus (HCV) all over the world,
      with an estimated 8-10 million among a population of 68 million having been
      exposed to the virus and 5-7 million active infections (Frank et al., 2000). It
      is considered the most common aetiology of chronic liver disease (CLD) in Egypt,
      where prevalence of antibodies to HCV (anti-HCV) is 10-fold greater than in the
      United States and Europe (Goldstone et al., 2002; Strickland et al., 2002). We
      have studied the role of plasma ghrelin, an orexigenic hormone that was found to
      correlate with malnourishment in CLD depending on Child classification. Sixty
      patients were divided in three groups according to Child classification and were
      compared to normal healthy controls (20 subjects). There was a highly significant
      correlation of plasma ghrelin and body mass index (BMI), mid arm circumference
      (MAC), waist circumference (WC) and tricuspid skin fold thickness (TSF). Also
      plasma ghrelin was specific and sensitive by the ROC curve analysis to BMI, which
      would indicate a new marker for malnourishment and possibility of a novel
      therapeutic approach.

PMID- 21872553
TI  - From movements to actions: two mechanisms for learning action sequences.
AB  - When other individuals move, we interpret their movements as discrete,
      hierarchically-organized, goal-directed actions. However, the mechanisms that
      integrate visible movement features into actions are poorly understood. Here, we
      consider two sequence learning mechanisms - transitional probability-based (TP)
      and position-based encoding computations - that have been studied extensively in
      the domain of language learning, and investigate their potential for integrating
      movements into actions. If these learning mechanisms integrate movements into
      actions, then they should create memory units that contain (i) movement
      information, (ii) information about the order in which movements occurred, and
      (iii) information allowing actions to be recognized from different viewpoints. We
      show that both mechanisms retain movement information. However, only the position
      based mechanism creates movement representations that are view-invariant and
      contain order information. The TP-based mechanism creates movement
      representations that are view-dependent and contain no order information. We
      therefore suggest that the TP-based mechanism is unlikely to play an important
      role for integrating movements into actions. In contrast, the position-based
      mechanism retains some of the types of information needed to represent goal
      directed actions, which makes it an attractive target for further research to
      explore what, if any, role it plays in the perception of goal-directed actions.

PMID- 21872554
TI  - Exposure to human pharmaceuticals Carbamazepine, Ibuprofen and Bezafibrate causes
      molecular effects in Dreissena polymorpha.
AB  - Carbamazepine (CBZ), Ibuprofen (IBU) and Bezafibrate (BEZ) were tested for their
      potential to bioaccumulate and provoke molecular changes in the non-target
      organism Dreissena polymorpha. mRNA changes of enzymes and other proteins
      involved in the prevention from protein damage (heat shock protein 70, hsp70) and
      oxidative stress (superoxide dismutase, SOD; catalase, CAT; metallothionein, MT),
      biotransformation (pi-class glutathione S-transferase, piGST; aryl hydrocarbon
      receptor, AH-R), elimination (P-glycoprotein, P-gp) and reversible protein
      posttranslational modification (protein phosphatase 2A, PP2A) served as molecular
      biomarkers. Mussels were exposed in a flow-through system to increasing
      concentrations of the three substances (1, 10, 100 and 1000 nM). The two lower
      concentrations correspond to environmentally relevant concentrations detected in
      surface and effluent waters, respectively. Measuring tissue concentration after
      one, four and seven days the uptake of CBZ and IBU by the mussels could be
      evidenced, whereas no accumulation data could be achieved for BEZ. The
      bioconcentration factor was highest for mussels exposed to the lowest CBZ and IBU
      concentrations, with 90 and 460-fold higher tissue concentration, respectively,
      after seven days. CBZ was the only substance tested which caused a significant
      increase in gill mRNA level of hsp70 after only one day exposure, evidencing the
      potential of CBZ to immediately provoke a stress condition and assumingly protein
      damage in gills. After longer exposure, mussels displayed down-regulated mRNA
      levels of hsp70 and SOD in gills, as well as of MT and P-gp in the digestive
      gland, hinting on an inhibitory character of CBZ. In IBU exposed mussels
      increased oxidant stress conditions were evidenced by induced mRNA levels in the
      digestive gland of CAT and MT, as well as SOD after one and four days,
      respectively. A concentration as found at sewage treatment plant effluents
      provoked an increase in transcript levels of piGST, suggesting enhanced need for
      biotransformation of IBU or by-products derived from oxidative stress. Also
      exposure to an environmentally relevant BEZ concentration provoked an immediate
      increase in piGST transcript level in the digestive gland followed by up
      regulated hsp70 after four and seven days evidencing a chronic stress condition
      for the mussels.

PMID- 21872555
TI  - Thyroid dysfunction in sea bass (Dicentrarchus labrax): underlying mechanisms and
      effects of polychlorinated biphenyls on thyroid hormone physiology and
      metabolism.
AB  - The current study examines the effect of subchronic exposure to a mixture of
      Aroclor standards on thyroid hormone physiology and metabolism in juvenile sea
      bass. The contaminant mixture was formulated to reflect the persistent organic
      pollution to which the European sea bass population could conceivably be exposed
      (0.3, 0.6 and 1.0 MUg Sigma7PCBs per g food pellets) and higher (10 MUg
      Sigma7PCBs per g food pellets). After 120 days of exposure, histomorphometry of
      thyroid tissue, muscular thyroid hormone concentration and activity of enzymes
      involved in metabolism of thyroid hormones were assessed. Mean concentrations of
      8, 86, 142, 214 and 2279 ng g(-1)ww (Sigma7 ICES PCB congeners) were determined
      after 120 days exposure. The results show that the effects of PCB exposures on
      the thyroid system are dose-dependent. Exposure to environmentally relevant doses
      of PCB (0.3-1.0 MUg Sigma7PCBs per g food pellets) induced a larger variability
      of the follicle diameter and stimulated hepatic T(4) outer ring deiodinase.
      Muscular thyroid hormone levels were preserved thanks to the PCB induced changes
      in T(4) dynamics. At 10 times higher concentrations (10 MUg Sigma7PCBs per g food
      pellets) an important depression of T(3) and T(4) levels could be observed which
      are apparently caused by degenerative histological changes in the thyroid tissue.

PMID- 21872557
TI  - Metal toxicity, uptake and bioaccumulation in aquatic invertebrates--modelling
      zinc in crustaceans.
AB  - We use published data on the different patterns of the bioaccumulation of zinc by
      three crustaceans, the caridean decapod Palaemon elegans, the amphipod Orchestia
      gammarellus and the barnacle Amphibalanus amphitrite, to construct comparative
      biodynamic models of the bioaccumulation of zinc into metabolically available and
      detoxified components of accumulated zinc in each crustacean under both field and
      laboratory toxicity test conditions. We then link these bioaccumulation models to
      the onset of toxic effects on exposure of the crustaceans to high dissolved zinc
      bioavailabilities, using the tenets that toxicity effects are related to the
      total uptake rate of the toxic metal, and that toxicity is not usually dependent
      on the total accumulated metal concentration but always on the concentration of
      accumulated metal that is metabolically available. We dismiss the general concept
      that there is a critical accumulated body concentration of a metal in an
      invertebrate at which toxicity ensues, except under specific circumstances
      involving a rare lack of storage detoxification of accumulated metal. We thus
      propose a theoretical framework that can be extended to other metals and other
      aquatic invertebrates (indeed other animals) to explain the variation in the
      relationship between bioaccumulated body concentrations and toxicity, and
      subsequently to predict this relationship in many other species for which we have
      bioaccumulation modelling data.

PMID- 21872556
TI  - Bioconcentration, metabolism and excretion of triclocarban in larval Qurt medaka
      (Oryzias latipes).
AB  - The antimicrobial triclocarban (TCC) is frequently found in personal care
      products and commonly observed in surface waters and sediments. Due to its long
      environmental persistence TCC accumulates in sewage sludge. It also shows a high
      unintended biological activity as a potent inhibitor of the soluble epoxide
      hydrolase (sEH) and may be an endocrine disruptor. In this study, we investigated
      bioconcentration, metabolism and elimination of TCC in fish using medaka (Oryzias
      latipes) as a model. Medaka larvae (7 +/- 1 days post hatching) were exposed to
      63 nM (20 MUg/L) TCC water for 24h. The LC-MS/MS analysis of water and tissues
      provided bioconcentration of TCC and its metabolites in fish body and rapid
      excretion into culture water. Results from tissue samples showed a tissue
      concentration of 34 MUmol/kg and a log bioconcentration factor (BCF) of 2.86.
      These results are slightly lower than previous findings in snails and algae. A
      significant portion of the absorbed TCC was oxidatively metabolized by the fish
      to hydroxylated products. These metabolites underwent extensive phase II
      metabolism to yield sulfate and glucuronic acid conjugates. The most abundant
      metabolite in fish tissue was the glucuronide of 2'-OH-TCC. Elimination of TCC
      after transferring the fish to fresh water was rapid, with a half-life of 1h.
      This study shows that larval medaka metabolize TCC similarly to mammals. The
      rapid rate of metabolism results in a lower bioconcentration than calculated from
      the octanol-water coefficient of TCC.

PMID- 21872558
TI  - Salvage liver transplantation for recurrent hepatocellular carcinoma after
      radiofrequency ablation: a new strategy?

PMID- 21872559
TI  - Myocardial performance is reduced immediately prior to ventricular ectopy.
AB  - BACKGROUND: We recently demonstrated local voltage potentials indicating
      conduction impairment and block in the sinus beats preceding ventricular
      premature beats (VPBs) originating in the ventricular outflow tracts. OBJECTIVE:
      The purpose of this study was to test the hypothesis that impairment of impulse
      conduction would also lead to changes in the contractile performance of sinus
      beats preceding ventricular ectopy using Tissue Doppler echocardiography.
      METHODS: Twenty-three consecutive patients with VPBs were examined in the apical
      4-chamber view with a frame rate of 150 Hz (GE VIVID VII). Eleven patients had no
      structural heart disease, 5 had dilated cardiomyopathy, 4 had ischemic heart
      disease, 2 had arrhythmogenic right ventricular dysplasia, and 1 had aortic
      stenosis. The ectopy originated in the ventricular outflow tracts in 15 patients
      and in the left ventricle 8. Eleven of the patients underwent radiofrequency
      ablation of the VPBs. RESULTS: Tissue Doppler imaging demonstrated a highly
      statistically significant decrease in myocardial performance in the last sinus
      beat before the VPB compared to earlier sinus beats. Thus, ejection time (time to
      peak end-systolic contraction) and peak systolic velocity shortened significantly
      (P <.001 for both) with a subsequent reduction in systolic shortening (end
      systolic displacement; P <.001). CONCLUSION: Ventricular ectopy is preceded by a
      significant decrease in myocardial performance in the last sinus beat preceding
      VPBs as observed in consecutive patients with a broad variety of heart conditions
      pointing to a mutual underlying electrical mechanism (ie, localized conduction
      block confined to an area surrounding the ectopic pacemaker).

PMID- 21872560
TI  - A novel radiofrequency ablation catheter using contact force sensing: Toccata
      study.
AB  - OBJECTIVES: The aim of this multicenter study was to evaluate the device- and
      procedure-related safety of a novel force-sensing radiofrequency (RF) ablation
      catheter capable of measuring the real-time contact force (CF) and to present CF
      data and its possible implications on patient safety. BACKGROUND: The clinical
      outcome of RF ablation for the treatment of cardiac arrhythmias may be affected
      by the CF between the catheter tip and the tissue. Insufficient CF may result in
      an ineffective lesion, whereas excessive CF may result in complications. METHODS:
      Seventy-seven patients (43 with right-sided supraventricular tachycardia [SVT]
      and 34 with atrial fibrillation [AF]) received percutaneous ablation with the
      novel studied catheter. The CF applied and safety events related to the procedure
      were reported. RESULTS: CF values at mapping ranged from 8 +/- 8 to 60 +/- 35 g
      and from 12 +/- 10 to 39 +/- 29 g in the SVT group and the LA group,
      respectively, showing a significant interinvestigator variability (P < .0001).
      High transient CFs (>100 g) were noted in 27 patients (79%) of the LA group. One
      device-related complication (tamponade, 3%) occurred in the AF group.
      CONCLUSIONS: Catheter ablation using real-time CF technology is safe for the
      treatment of SVT and AF. High CFs may occur during catheter manipulation and not
      just during ablation, suggesting that measuring CF may provide additional useful
      information to the operator for safe catheter manipulation. In the future, CF
      sensing catheters may also increase the effectiveness of RF ablations by allowing
      better control of the RF lesion size.

PMID- 21872561
TI  - Novel method of signal analysis for ablation of Wolff-Parkinson-White syndrome.
AB  - BACKGROUND: Identification of the site of successful radiofrequency catheter
      ablation (RFCA) for Wolff-Parkinson-White (WPW) syndrome may be subjective.
      OBJECTIVE: The purpose of this study was to develop an automated signal analysis
      program to predict a successful ablation site. METHODS: Patients who underwent
      successful RFCA for WPW from 2008- 2010 at our center were analyzed. Inclusion
      criteria were age <21 years, loss of preexcitation in <5 seconds, and sustained
      success at 3 months. Exclusion criteria were congenital heart disease and pacing
      during RFCA. The standard recording system signal was filtered into low frequency
      (LF 0-<=0.02 Hz) and high frequency (HF >0.02-<=0.45 Hz). Software identified the
      beginning of the HF signal, LF and R-wave peaks, LF/HF signal amplitude, and area
      under the HF/LF signals. Successful and unsuccessful (radiofrequency energy
      applied without accessory pathway block) signals were compared. RESULTS: Thirty
      patients were analyzed; 16 had both successful and unsuccessful signals, and 14
      had a successful ablation with 1 radiofrequency application. Mean age was 13.7 +/
      3.1 years, weight 54.9 +/- 22.4 kg, and time to accessory pathway ablation 1.7
      +/- 1.4 seconds. Significant differences were found between successful and
      unsuccessful signals in area under HF signal, LF amplitude, LF to R time, HF
      ratio, and HF area * HF ratio. A receiver operating curve of HF area * HF ratio
      produced an area under the curve of 0.89. An HF area * HF ratio of 3.1
      distinguished successful from unsuccessful signals with 100% specificity and 81%
      sensitivity. CONCLUSION: Automated signal analysis retrospectively differentiated
      successful from unsuccessful signals in patients undergoing RFCA for WPW. This
      software may improve the safety and efficacy of RFCA in children.

PMID- 21872562
TI  - Stimulation of adult oligodendrogenesis by myelin-specific T cells.
AB  - In multiple sclerosis (MS), myelin-specific T cells are normally associated with
      destruction of myelin and axonal damage. However, in acute MS plaque,
      remyelination occurs concurrent with T-cell infiltration, which raises the
      question of whether T cells might stimulate myelin repair. We investigated the
      effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal
      damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for
      myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2
      expressing oligodendrocyte precursor cells early after induction via axonal
      transection, resulting in a 25% increase in the numbers of oligodendrocytes. In
      contrast, T cells specific for ovalbumin did not stimulate the formation of new
      oligodendrocytes. In addition, infiltration of myelin-specific T cells enhanced
      the sprouting response of calretinergic associational/commissural fibers within
      the dentate gyrus. These results have implications for the perception of MS
      pathogenesis because they show that infiltrating myelin-specific T cells can
      stimulate oligodendrogenesis in the adult central nervous system.

PMID- 21872563
TI  - Interleukin-34 selectively enhances the neuroprotective effects of microglia to
      attenuate oligomeric amyloid-beta neurotoxicity.
AB  - Microglia, macrophage-like resident immune cells in the brain, possess both
      neurotoxic and neuroprotective properties and have a critical role in the
      development of Alzheimer's disease (AD). We examined the function of Interleukin
      34 (IL-34), a newly discovered cytokine, on microglia because it reportedly
      induces proliferation of monocytes and macrophages. We observed that the neuronal
      cells primarily produce IL-34 and that microglia express its receptor, colony
      stimulating factor 1 receptor. IL-34 promoted microglial proliferation and
      clearance of soluble oligomeric amyloid-beta (oAbeta), which mediates synaptic
      dysfunction and neuronal damage in AD. IL-34 increased the expression of insulin
      degrading enzyme, aiding the clearance of oAbeta, and induced the antioxidant
      enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without
      producing neurotoxic molecules. Consequently, microglia treated with IL-34
      attenuated oAbeta neurotoxicity in primary neuron-microglia co-cultures. In vivo,
      intracerebroventricular administration of IL-34 ameliorated impairment of
      associative learning and reduced oAbeta levels through up-regulation of insulin
      degrading enzyme and heme oxygenase-1 in an APP/PS1 transgenic mouse model of AD.
      These findings support the idea that enhancement of the neuroprotective property
      of microglia by IL-34 may be an effective approach against oAbeta neurotoxicity
      in AD.

PMID- 21872565
TI  - Five-minute glycoprotein sialic acid determination by high-performance anion
      exchange chromatography with pulsed amperometric detection.
AB  - Glycoprotein sialylation analysis is a common analytical step in characterizing
      biotherapeutic products and expression experiments to optimize production. In
      this article, a high-throughput (5-min) high-performance anion exchange
      chromatography with pulsed amperometric detection (HPAE-PAD)-based analytical
      method for glycoprotein sialic acid determination is described. Results from this
      method are compared with both published HPAE-PAD and 1,2-diamino-4,5
      methylenedioxybenzene (DMB) derivatization followed by ultra high-performance
      liquid chromatography fluorescence detection (UHPLC-FLD) assays. The quantified
      sialic acid amounts agree with prior HPAE-PAD analyses within replicate error and
      with UHPLC-FLD within an average of 24%, which are equivalent results based on
      assay reproducibility.

PMID- 21872564
TI  - Identification and characterization of cartilage oligomeric matrix protein as a
      novel pathogenic factor in keloids.
AB  - To elucidate pathogenic molecules in keloids, microarray analysis was performed
      using RNAs extracted from keloid-derived fibroblasts and normal skin-derived
      fibroblasts from the same patient with a typical keloid. Among 11 up-regulated
      extracellular matrix genes, cartilage oligomeric matrix protein (COMP) was most
      prominently increased. Up-regulation of COMP mRNA and protein was confirmed in
      the keloid tissue by quantitative RT-PCR and Western blot. Using
      immunohistochemistry, we compared 15 keloids and 6 control normal tissues using a
      COMP-specific antibody and found that COMP stained positively in 10 keloids
      (66.7%), whereas no staining was observed in normal tissues, demonstrating the
      ectopic expression of COMP in keloids. Comparing keloids smaller or larger than
      10 cm(2), the larger keloids were significantly more intensely stained with the
      COMP-specific antibody. Because COMP reportedly accelerates collagen type I
      fibril assembly, we examined whether extracellular type I collagen deposition is
      altered by silencing COMP mRNA by small interfering RNA (siRNA).
      Immunocytochemistry showed at 96 hours after transfection with COMP siRNA that
      the extracellular deposition of type I collagen was decreased compared to that
      observed with control siRNA. Further, COMP knockdown decreased amount collagens
      type I to V in the medium and on the cell surfaces. Our data suggest that COMP
      facilitates keloid formation by accelerating collagen deposition, thus providing
      a new therapeutic target.

PMID- 21872566
TI  - Fluorescent high-performance liquid chromatography assay for lipophilic alcohols.
AB  - A new ultrasensitive fluorescent derivatization procedure for chromatographic
      analysis of primary, secondary, and nonpolar tertiary alcohols is described. The
      procedure uses Bodipy FL in basic dichloromethane solution with Mukaiyama's
      reagent (2-chloro-1-methylpyridinium iodide) to form highly fluorescent ester
      derivatives that can be separated by silica normal-phase high-performance liquid
      chromatography (HPLC). Rhodamine WT and Oregon green 488 were also useful
      derivatization reagents. The detection limit for detection of cholesterol and
      bryostatin by Bodipy FL was less than 1fmol. The reaction conditions are gentle
      enough that low concentrations of unstable alcohols such as bryostatin 1 can be
      measured.

PMID- 21872568
TI  - A reinterpretation of neutron scattering experiments on a lipidated Ras peptide
      using replica exchange molecular dynamics.
AB  - The Ras family of proteins plays crucial roles in a variety of cell signaling
      networks where they have the function of a molecular switch. Their particular
      medical relevance arises from mutations in these proteins that are implicated in
      ~30% of human cancers. The various Ras proteins exhibit a high degree of homology
      in their soluble domains but extremely high variability in the membrane anchoring
      regions that are crucial for protein function and are the focus of this study. We
      have employed replica exchange molecular dynamics computer simulations to study a
      doubly lipidated heptapeptide, corresponding to the C-terminus of the human N-Ras
      protein, incorporated into a dimyristoylphosphatidylcholine lipid bilayer. This
      same system has previously been investigated experimentally utilizing a number of
      techniques, including neutron scattering. Here we present results of well
      converged simulations that describe the subtle changes in scattering density in
      terms of the location of the peptide and its lipid modifications and in terms of
      changes in phospholipid density arising from the incorporation of the peptide
      into the membrane bilayer. The detailed picture that emerges from the combination
      of experimental and computational data exemplifies the power of combining
      isotopic substitution neutron scattering with atomistic molecular dynamics
      simulation. This article is part of a Special Issue entitled: Membrane protein
      structure and function.

PMID- 21872567
TI  - High efficiency of energy flux controls within mitochondrial interactosome in
      cardiac intracellular energetic units.
AB  - The aim of our study was to analyze a distribution of metabolic flux controls of
      all mitochondrial complexes of ATP-Synthasome and mitochondrial creatine kinase
      (MtCK) in situ in permeabilized cardiac cells. For this we used their specific
      inhibitors to measure flux control coefficients (C(vi)(JATP)) in two different
      systems: A) direct stimulation of respiration by ADP and B) activation of
      respiration by coupled MtCK reaction in the presence of MgATP and creatine. In
      isolated mitochondria the C(vi)(JATP) were for system A: Complex I - 0.19,
      Complex III - 0.06, Complex IV 0.18, adenine nucleotide translocase (ANT) - 0.11,
      ATP synthase - 0.01, Pi carrier - 0.20, and the sum of C(vi)(JATP) was 0.75. In
      the presence of 10mM creatine (system B) the C(vi)(JATP) were 0.38 for ANT and
      0.80 for MtCK. In the permeabilized cardiomyocytes inhibitors had to be added in
      much higher final concentration, and the following values of C(vi)(JATP) were
      determined for condition A and B, respectively: Complex I - 0.20 and 0.64,
      Complex III - 0.41 and 0.40, Complex IV - 0.40 and 0.49, ANT - 0.20 and 0.92, ATP
      synthase - 0.065 and 0.38, Pi carrier - 0.06 and 0.06, MtCK 0.95. The sum of
      C(vi)(JATP) was 1.33 and 3.84, respectively. Thus, C(vi)(JATP) were specifically
      increased under conditions B only for steps involved in ADP turnover and for
      Complex I in permeabilized cardiomyocytes within Mitochondrial Interactosome, a
      supercomplex consisting of MtCK, ATP-Synthasome, voltage dependent anion channel
      associated with tubulin betaII which restricts permeability of the mitochondrial
      outer membrane.

PMID- 21872569
TI  - The effect of anions on the human P2X7 receptor.
AB  - P2X7 receptors (P2X7Rs) are nonselective cation channels that are opened by the
      binding of extracellular ATP and are involved in the modulation of epithelial
      secretion, inflammation and nociception. Here, we investigated the effect of
      extracellular anions on channel gating and permeation of human P2X7Rs (hP2X7Rs)
      expressed in Xenopus laevis oocytes. Two-microelectrode voltage-clamp recordings
      showed that ATP-induced hP2X7R-mediated currents increased when extracellular
      chloride was substituted by the organic anions glutamate or aspartate and
      decreased when chloride was replaced by the inorganic anions nitrate, sulfate or
      iodide. ATP concentration-response comparisons revealed that substitution of
      chloride by glutamate decreased agonist efficacy, while substitution by iodide
      increased agonist efficacy at high ATP concentrations. Meanwhile, the ATP potency
      remained unchanged. Activation of the hP2X7R at low ATP concentrations via the
      high-affinity ATP effector site was not affected by the replacement of chloride
      by glutamate or iodide. To analyze the anion effect on the hP2X7R at the single
      molecule level, we performed single-channel current measurements using the patch
      clamp technique in the outside-out configuration. Chloride substitution did not
      affect the single-channel conductance, but the probability that the P2X7R channel
      was open increased when chloride was replaced by glutamate and decreased when
      chloride was replaced by iodide. This effect was due to an influence of the
      anions on the mean closed times of the hP2X7R channel. We conclude that hP2X7R
      channels are not anion-permeable in physiological Na+-based media and that
      external anions allosterically affect ion channel opening in the fully ATP4
      liganded P2X7R through an extracellular anion binding site.

PMID- 21872570
TI  - Diverse gating in K+ channels: differential role of the pore-helix glutamate in
      stabilizing the channel pore.
AB  - The selectivity filter and adjacent regions in the bacterial KcsA and inwardly
      rectifying K(+) (Kir) channels reveal significant conformational changes that
      cause the channel pore to transition from an activated to inactive state (C-type
      inactivation) once the channel is open. The meshwork of residues stabilizing the
      pore of KcsA involves Glu71-Asp80 carboxyl-carboxylate interaction 'behind' the
      selectivity filter. Interestingly, the Kir channels do not have this exact
      interaction, but instead have a Glu-Arg salt bridge where the Glu is in the same
      position but the Arg is one position N-terminal compared to the Asp in KcsA.
      Also, the Kir channels lack the Trp that hydrogen bonds to Asp80 in KcsA. Here,
      the sequence and structural information are combined to understand the
      dissimilarity in the role of the pore-helix Glu in stabilizing the pore structure
      in KcsA and Kir channels. This review illustrates that although Glu is quite
      conserved among both types of channels, the network of interactions is not
      translatable from one channel to the other; thereby suggesting a unique
      phenomenon of diverse gating patterns in K(+) channels.

PMID- 21872571
TI  - Co-existence of major and minor viral populations from two different origins in
      patients secondarily infected with dengue virus serotype 2 in Bangkok.
AB  - Generally, RNA viruses exhibit significant genetic diversity that sometimes
      effect viral fitness in infected hosts and probably also pathogenesis. Dengue
      viruses (DENVs) consist of four antigenically distinct serotypes. All the
      serotypes of DENV can cause mild to severe dengue illnesses. In this study, we
      examined the sequence variation of DENV in plasma obtained from four patients
      living in Bangkok who had been secondarily infected with serotype 2 (DENV-2) in
      2010. The plasma-derived RNA was directly subjected to reverse transcriptase (RT)
      polymerase chain reaction (PCR) at a region including most of domain III of the
      envelope (E) protein gene, and the PCR products obtained were subjected to clonal
      sequencing. Using 19-20 clones sequenced from each patient (78 total) plus 601
      corresponding sequences from a public database, phylogenetic analysis revealed
      that the nucleic acid sequences fell into two clusters with clearly different
      origins. Interestingly, all patients gave sequences indicating that they carried
      viral populations containing 2, 3 or 5 genetic variants that consisted of one
      major variant plus one or more minor variants. Three patients showed a major
      variant from one cluster plus one or more minor components from the other while
      one showed major and minor variants from a single cluster. Thus, it can be
      concluded that DENV belonging to two different genetic lineages were co
      circulated in Bangkok in 2010. For these two genotype clusters there was also a
      clear difference in H or Y at the deduced amino acid position 346 (i.e. H346Y)
      that was consistent for our sequences and 601 sequences from the public database.
      Thus, one among the mixed viral genotypes introduced into human individuals seems
      to be variably selected as the predominant component of the carried viral
      population, and it is possible that the dynamics of this process could influence
      virus evolution and disease severity.

PMID- 21872572
TI  - Src family protein tyrosine kinases modulate L-type calcium current in human
      atrial myocytes.
AB  - In the heart, L-type voltage dependent calcium channels (L-VDCC) provide Ca(2+)
      for the activation of contractile apparatus. The best described pathway for L
      type Ca(2+) current (I(Ca,L)) modulation is the phosphorylation of calcium
      channels by cAMP-dependent protein kinase A (PKA), the activity of which is
      predominantly regulated in opposite manner by beta-adrenergic (beta-ARs) and
      muscarinic receptors. The role of other kinases is controversial and often
      depends on tissues and species used in the studies. In different studies the
      inhibitors of tyrosine kinases have been shown either to stimulate or inhibit, or
      even have a biphasic effect on I(Ca,L). Moreover, there is no clear picture about
      the route of activation and the site of action of cardiac Src family nonreceptor
      tyrosine kinases (Src-nPTKs). In the present study we used PP1, a selective
      inhibitor of Src-nPTKs, alone and together with different activators of I(Ca,L),
      and demonstrated that in human atrial myocytes (HAMs): (i) Src-nPTKs are
      activated concomitantly with activation of cAMP-signaling cascade; (ii) Src-nPTKs
      attenuate PKA-dependent stimulation of I(Ca,L) by inhibiting PKA activity; (iii)
      Galpha(s) are not involved in the direct activation of Src-nPTKs. In this way,
      Src-nPTKs may provide a protecting mechanism against myocardial overload under
      conditions of increased sympathetic activity.

PMID- 21872573
TI  - Bacterial persisters tolerate antibiotics by not producing hydroxyl radicals.
AB  - In a phenomenon called persistence, small numbers of bacterial cells survive even
      after exposure to antibiotics. Recently, bactericidal antibiotics have been
      demonstrated to kill bacteria by increasing the levels of hydroxyl radicals
      inside cells. In the present study, we report a direct correlation between
      intracellular hydroxyl radical formation and bacterial persistence. By conducting
      flow cytometric analysis in a three-dimensional space, we resolved distinct
      bacterial populations in terms of intracellular hydroxyl radical levels,
      morphology and viability. We determined that, upon antibiotic treatment, a small
      sub-population of Escherichia coli survivors do not overproduce hydroxyl radicals
      and maintain normal morphology, whereas most bacterial cells were killed by
      accumulating hydroxyl radicals and displayed filamentous morphology. Our results
      suggest that bacterial persisters can be formed once they have transient defects
      in mediating reactions involved in the hydroxyl radical formation pathway. Thus,
      it is highly probable that persisters do not share a common mechanism but each
      persister cell respond to antibiotics in different ways, while they all commonly
      show lowered hydroxyl radical formation and enhanced tolerance to antibiotics.

PMID- 21872574
TI  - Mass-spectrometric characterization of peroxidized and hydrolyzed lipids in
      plasma and dendritic cells of tumor-bearing animals.
AB  - Dendritic cells are the most potent antigen presenting cells responsible for the
      development of immune responses in cancer. However, it is known that the function
      of dendritic cells in tumor-bearing hosts is severely compromised. Our previous
      studies demonstrated that the defects in dendritic cell function are due, to a
      large extent, to the accumulation of high amounts of lipids--predominantly
      triglycerides--in a substantial proportion of dendritic cells in tumor-bearing
      mice and patients with cancer. The dendritic cells accumulation of lipids is
      likely associated with their up-regulation of a scavenger receptor A. This
      receptor is primarily responsible for uptake of modified lipids. Here, by using
      different versions of liquid chromatography-mass spectrometry, we identified
      several molecular species of oxygenated lipids in plasma of tumor-bearing animals
      that may be responsible for their uptake and accumulation by dendritic cells via
      scavenger receptor A-dependent pathway--the effect that may be associated with
      the loss of dendritic cell's immune surveillance function in cancer.

PMID- 21872575
TI  - AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway.
AB  - Vascular cells have a limited lifespan with limited cell proliferation and
      undergo cellular senescence. The functional changes associated with cellular
      senescence are thought to contribute to age-related vascular disorders. AMP
      activated protein kinase (AMPK) has been discussed in terms of beneficial or
      harmful effects for aging-related diseases. However, the detailed functional
      mechanisms of AMPK are largely unclear. An aging model was established by
      stimulating vascular smooth muscle cell (VSMC) with adriamycin. Adriamycin
      progressively increased the mRNA and protein expressions of AMPK. The
      phosphorylation levels of LKB1 and acetyl-CoA carboxylase (ACC), the upstream and
      downstream of AMPK, were dramatically increased by adriamycin stimulation. The
      expressions of p53 and p21, which contribute to vascular senescence, were also
      increased. Inhibition of AMPK diminished senescence-associated beta-galactosidase
      (SA-beta-gal) staining, and restored VSMC proliferation. Cytosolic translocation
      of LKB1 by adriamycin could be a mechanism for AMPK activation in senescence.
      Furthermore, p53 siRNA and p21 siRNA transfection attenuated adriamycin-induced
      SA-beta-gal staining. These results suggest that LKB1 dependent AMPK activation
      elicits VSMC senescence and p53-p21 pathway is a mediator of LKB1/AMPK-induced
      senescence.

PMID- 21872576
TI  - Ganglioside mediate the interaction between Nogo receptor 1 and LINGO-1.
AB  - Upon spinal cord injury, the myelin inhibitors, including the myelin-associated
      glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp),
      bind to and signal via a single neuronal receptor/co-receptor complex comprising
      of Nogo receptor 1(NgR1)/LINGO-1 and p75 or TROY, impeding regeneration of
      injured axons. We employed a cell-free system to study the binding of NgR1 to its
      co-receptors and the myelin inhibitor Nogo-A, and show that gangliosides mediate
      the interaction of NgR1 with LINGO-1. Solid phase binding assays demonstrate that
      the sialic acid moieties of gangliosides and the stalk of NgR1 are the principal
      determinants of these molecular interactions. Moreover, the tripartite complex
      comprising of NgR1, LINGO-1 and ganglioside exhibits stronger binding to Nogo-A
      (Nogo-54) in the presence of p75, suggesting the gangliosides modulate the myelin
      inhibitor-receptor signaling.

PMID- 21872577
TI  - Activation of sphingosine kinase 2 is an endogenous protective mechanism in
      cerebral ischemia.
AB  - The two ubiquitously expressed sphingosine kinases (SphK) 1 and 2 are key
      regulators of the sphingolipid signaling pathway. Despite the formation of an
      identical messenger, i.e. sphingosine 1-phosphate (S1P), they exert strikingly
      different functions. Particularly, SphK2 is necessary for the phosphorylation of
      the sphingosine analog fingolimod (FTY720), which is protective in rodent stroke
      models. Using gene deficient mice lacking either SphK1 or SphK2, we investigated
      the role of the two lipid kinases in experimental stroke. We performed 2h
      transient middle cerebral artery occlusion (tMCAO) and analyzed lesion size and
      neurological function after 24h. Treatment groups received 1mg/kg FTY720.
      Neutrophil infiltration, microglia activation, mRNA and protein expression of
      SphK1, SphK2 and the S1P(1) receptor after tMCAO were studied. Genetic deletion
      of SphK2 but not SphK1 increased ischemic lesion size and worsened neurological
      function after tMCAO. The protective effect of FTY720 was conserved in SphK1(-/-)
      mice but not in SphK2(-/-) mice. This suggests that SphK2 activity is an
      important endogenous protective mechanism in cerebral ischemia and corroborates
      that the protective effect of FTY720 is mediated via phospho-FTY720.

PMID- 21872578
TI  - Triage of oxidation-prone proteins by Sqstm1/p62 within the mitochondria.
AB  - As the mitochondrion is vulnerable to oxidative stress, cells have evolved
      several strategies to maintain mitochondrial integrity, including mitochondrial
      protein quality control mechanisms and autophagic removal of damaged
      mitochondria. Involvement of an autophagy adaptor, Sqstm1/p62, in the latter
      process has been recently described. In the present study, we provide evidence
      that a portion of p62 directly localizes within the mitochondria and supports
      stable electron transport by forming heterogeneous protein complexes. Matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF)
      of mitochondrial proteins co-purified with p62 revealed that p62 interacts with
      several oxidation-prone proteins, including a few components of the electron
      transport chain complexes, as well as multiple chaperone molecules and redox
      regulatory enzymes. Accordingly, p62-deficient mitochondria exhibited compromised
      electron transport, and the compromised function was partially restored by in
      vitro delivery of p62. These results suggest that p62 plays an additional role in
      maintaining mitochondrial integrity at the vicinity of target machineries through
      its function in relation to protein quality control.

PMID- 21872579
TI  - Importance of PIKKs in NF-kappaB activation by genotoxic stress.
AB  - Alteration of the genome integrity leads to the activation of a vast network of
      cellular responses named "DNA damage response". Three kinases from the
      phosphoinositide 3-kinase-like protein kinase family regulate this network; ATM
      and DNA-PK both activated by DNA double-strand breaks and ATR activated by
      replication blocks. "DNA damage response" pathway coordinates cell cycle arrest,
      DNA repair, and the activation of transcription factors such as p53 and NF
      kappaB. It controls senescence/apoptosis/survival of the damaged cells. Cell
      death or survival result from a tightly regulated balance between antagonist pro-
      and anti-apoptotic signals. NF-kappaB is a key transcription factor involved in
      immunity, inflammation and cell transformation. When activated by DNA double
      strand breaks, NF-kappaB has most often a pro-survival effect and thereof
      interferes with chemotherapy treatments that often rely on DNA damage to induce
      tumor cell death (i.e. topoisomerase inhibitors and ionizing radiation). NF
      kappaB is thus an important pharmaceutical target. Agents leading to replication
      stress induce a pro-apoptotic NF-kappaB. The molecular mechanisms initiated by
      DNA lesions leading to NF-kappaB nuclear translocation have been extensively
      studied these last years. In this review, we will focus on ATM, ATR and DNA-PK
      functions both in the IKKalpha/IKKbeta/NEMO-dependent or -independent signaling
      pathways and on the regulation they can exercise at the promoter level of NF
      kappaB regulated genes.

PMID- 21872580
TI  - Cell cycle arrest and apoptosis induced by methyl 3,5-dicaffeoyl quinate in human
      colon cancer cells: Involvement of the PI3K/Akt and MAP kinase pathways.
AB  - Methyl 3,5-dicaffeoyl quinate (MDQ) is a flavonoid glucoside found in several
      plants that scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and
      peroxynitrite, and inhibits the formation of cholesteryl ester hydroperoxide
      during the copper ion-induced oxidation of blood plasma in rats. In this study,
      MDQ inhibited proliferation and induced apoptosis in HT-29 cells in a dose
      dependent manner as detected by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan
      (MTT), trypan blue exclusion, and flow cytometric assays. Western blot analysis
      showed that apoptosis was dependent on caspase-3 activity. PARP cleavage and the
      cytosolic release of cytochrome c from mitochondria increased significantly. In
      addition, these events were accompanied by a collapse in the mitochondrial
      membrane potential and a decreased Bcl-2/Bax ratio. Furthermore, the MDQ-induced
      G(0)/G(1) arrest was correlated with an increase in p27 and a decrease in cyclin
      D1 and p53. MDQ also inhibited the phosphorylation of PI3K/Akt and ERK;
      significantly reduced NF-kappaB; and in general displayed a significant anti
      proliferative effect via a cell cycle arrest and apoptotic induction in HT-29
      cells. These results suggest that MDQ has therapeutic potential against human
      colon carcinoma.

PMID- 21872581
TI  - Phase structure of liposome in lipid mixtures.
AB  - Gas microbubbles present in ultrasound imaging contrast agents are stabilized by
      lipid aggregates that typically contain a mixture of lipids. In this study, the
      phase structure of the lipid mixtures that contained two or three lipids was
      investigated using three different methods: dynamic light scattering, (1)H NMR,
      and microfluidity measurements with fluorescence probes. Three lipids that are
      commonly present in imaging agents (DPPC, DPPE-PEG, and DPPA) were used. Two
      types of systems, two-lipid model systems and simulated imaging systems were
      investigated. The results show that liposomes were the dominant aggregates in all
      the samples studied. The polar PEG side chains from the PEGylated lipid lead to
      the formation of micelles and micellar aggregates in small sizes. In the ternary
      lipid systems, almost all the lipids were present in bilayers with micelles
      absent and free lipids at very low concentration. These results suggest that
      liposomes, not micelles, contribute to the stabilization of microbubbles in an
      ultrasound imaging contrast agent.

PMID- 21872582
TI  - The effect of morphine sensitization on extracellular concentrations of GABA in
      dorsal hippocampus of male rats.
AB  - Repeated, intermittent exposure to drugs of abuse, such as morphine results in
      response enhancements to subsequent drug treatments, a phenomenon referred to as
      behavioral sensitization. As persistent neuronal sensitization may contribute to
      the long-lasting consequences of drug abuse, characterizing the neurochemical
      mechanisms of sensitization is providing insights into addiction. Although it has
      been shown that GABAergic systems in the CA1 region of dorsal hippocampus are
      involved in morphine sensitization, the alteration of extracellular level of GABA
      in this area in morphine sensitization has not been investigated. In the present
      study, using the in vivo microdialysis technique, we investigated the effect of
      morphine sensitization on extracellular GABA concentration in CA1 region of
      dorsal hippocampus of freely moving rats. Sensitization was induced by
      subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5
      days free of the opioid treatment. The results showed that extracellular GABA
      concentration in CA1 was decreased following acute administration of morphine in
      non-sensitized rats. However, morphine-induced behavioral sensitization
      significantly increased the extracellular GABA concentration in this area. The
      enhancement of GABA in morphine sensitized rats was inhibited by administration
      of naloxone 30 min before each of three daily doses of morphine. These results
      suggest an adaptation of the GABAergic neuronal transmission in dorsal
      hippocampus induced by morphine sensitization and it is implied that opioid
      receptors may play an important role in this effect.

PMID- 21872583
TI  - Curine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca2+ channels and
      decreases intracellular Ca2+ transients in A7r5 cells.
AB  - Curine is a novel bisbenzylisoquinoline alkaloid that has previously been
      reported as a vasodilator. The underlying mechanism(s) of the vasodilator effect
      of curine remains to be characterized. In this study, we investigated the
      cellular mechanism that is responsible for the vasodilator effect of curine in
      the rat aorta. The vasorelaxant activity of curine was recorded using a myograph.
      Ca(2+) currents in A7r5 cells were measured using the whole-cell patch-clamp
      technique. Intracellular Ca(2+) transients were determined using confocal
      microscopy. In a concentration-dependent manner, curine inhibited contractions
      elicited by high extracellular K(+) and Bay K8644 in the rat aorta and reduced
      the rise in the intracellular Ca(2+) concentration induced by membrane
      depolarization in response to an increase in extracellular K(+) concentration in
      vascular smooth muscle cells. Moreover, curine decreased the peak amplitude of L
      type Ca(2+) currents (I(Ca,L)) in a concentration-dependent manner without
      changing the characteristics of the current density vs. voltage relationship and
      the steady-state activation of I(Ca,L). Furthermore, curine shifted the steady
      state inactivation curve of I(Ca,L) toward more hyperpolarized membrane
      potentials. None of the following modified the effect of curine on I(Ca,L)
      amplitude: 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterases;
      dibutyryl cyclic AMP, an activator of protein kinase A (PKA); or 8-Br-cyclic GMP,
      an activator of protein kinase G (PKG). Our results showed that curine inhibited
      the L-type voltage-dependent Ca(2+) current in rat aorta smooth muscle cells,
      which caused a decrease in intracellular global Ca(2+) transients that led to
      vasorelaxation.

PMID- 21872584
TI  - Liquiritigenin attenuates the learning and memory deficits in an amyloid protein
      precursor transgenic mouse model and the underlying mechanisms.
AB  - The present paper is to examine whether liquiritigenin is able to attenuate the
      Alzheimer's-like learning and memory deficits in a transgenic (Tg) mouse model
      that over-expresses amyloid protein precursor (APP), and explores the underlying
      mechanisms. Consistent with our previous observations, we found that treatment
      with liquiritigenin improved the behavioral performance of Tg mice and it
      attenuated the protein expression of oligomeric form of amyloid beta-peptide
      (Abeta). Furthermore, treatment with liquiritigenin inhibited astrocytosis in the
      hippocampus, and it may through its inhibitory activities on Notch-2, an
      important molecular regulating neural proliferation and differentiation. These
      findings provide evidence for beneficial activity of liquiritigenin in a mouse
      model of Alzheimer's disease and support the continued investigation of Notch
      signaling pathway as a target for treatment of Alzheimer's disease.

PMID- 21872585
TI  - Prostaglandin D2 induces contractions through activation of TP receptors in
      peripheral lung tissue from the guinea pig.
AB  - Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a
      non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing
      effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as
      well as the thromboxane receptor TP, the aim of this study was to characterize
      the receptors that are activated by PGD(2) in the guinea pig lung parenchyma.
      PGD(2) and the thromboxane analog U46619 induced concentration-dependent
      contractions. U46619 was more potent and caused stronger effect than PGD(2). The
      specific TP receptor antagonist SQ-29548 and the combined TP and DP(2) receptor
      antagonist BAYu3405 concentration-dependently shifted the curves for both
      agonists to the right. The DP(1) receptor agonist BW245 induced a weak relaxation
      at high concentrations, whereas the DP(1) receptor antagonist BWA868C did not
      affect the PGD(2) induced contractions. The specific DP(2) receptor agonist 13,14
      dihydro-15-keto-PGD(2) showed neither contractile nor relaxant effect in the
      parenchyma. Furthermore, studies in precision-cut lung slices specified that
      airways as well as pulmonary arteries and veins contracted to both PGD(2) and
      U46619. When the lung parenchyma from ovalbumin sensitized guinea pigs were
      exposed to ovalbumin, both thromboxane B(2) and PGD(2) were released. Ovalbumin
      also induced maximal contractions at similar level as PGD(2) in the parenchyma,
      which was partly reduced by SQ-29548. These data show that PGD(2) should be
      recognized as a TP receptor agonist in the peripheral lung inducing contraction
      on airways, arteries and veins. Therefore, a TP receptor antagonist can be useful
      in combination treatment of allergic responses in asthma.

PMID- 21872586
TI  - Dopamine antagonists and brief vision distinguish lens-induced- and form
      deprivation-induced myopia.
AB  - In eyes wearing negative lenses, the D2 dopamine antagonist spiperone was only
      partly effective in preventing the ameliorative effects of brief periods of
      vision (Nickla et al., 2010), in contrast to reports from studies using form
      deprivation. The present study was done to directly compare the effects of
      spiperone, and the D1 antagonist SCH-23390, on the two different myopiagenic
      paradigms. 12-day old chickens wore monocular diffusers (form-deprivation) or -10
      D lenses attached to the feathers with matching rings of Velcro. Each day for 4
      days, 10 MUl intravitreal injections of the dopamine D2/D4 antagonist spiperone
      (5 nmoles) or the D1 antagonist SCH-23390, were given under isoflurane
      anesthesia, and the diffusers (n = 16; n = 5, respectively) or lenses (n = 20; n
      = 6) were removed for 2 h immediately after. Saline injections prior to vision
      were done as controls (form-deprivation: n = 11; lenses: n = 10). Two other
      saline-injected groups wore the lenses (n = 12) or diffusers (n = 4)
      continuously. Axial dimensions were measured by high frequency A-scan
      ultrasonography at the start, and on the last day immediately prior to, and 3 h
      after the injection. Refractive errors were measured at the end of the experiment
      using a Hartinger's refractometer. In form-deprived eyes, spiperone, but not SCH
      23390, prevented the ocular growth inhibition normally effected by the brief
      periods of vision (change in vitreous chamber depth, spiperone vs saline: 322 vs
      211 MUm; p = 0.01). By contrast, neither had any effect on negative lens-wearing
      eyes given similar unrestricted vision (210 and 234 MUm respectively, vs 264
      MUm). The increased elongation in the spiperone-injected form-deprived eyes did
      not, however, result in a myopic shift, probably due to the inhibitory effect of
      the drug on anterior chamber growth (drug vs saline: 96 vs 160 MUm; p < 0.01).
      Finally, spiperone inhibited the vision-induced transient choroidal thickening in
      form-deprived eyes, while SCH-23390 did not. These results indicate that the
      dopaminergic mechanisms mediating the protective effects of brief periods of
      unrestricted vision differ for form-deprivation versus negative lens-wear, which
      may imply different growth control mechanisms between the two.

PMID- 21872587
TI  - A gamma band specific role of the subthalamic nucleus in switching during verbal
      fluency tasks in Parkinson's disease.
AB  - OBJECTIVE: Decline in verbal fluency is the most consistent and persistent
      cognitive impairment documented after deep brain stimulation of the subthalamic
      nucleus in Parkinson's disease. The mechanisms of this deficit are unclear. We
      aimed to identify and characterise verbal fluency related processing within the
      subthalamic nucleus through analysis of local field potentials. METHODS: Local
      field potentials were recorded from deep brain stimulation electrodes implanted
      in the subthalamic nuclei of 8 patients (16 sides) with Parkinson's disease, when
      patients were on medication. Patients performed phonemic and semantic verbal
      fluency tasks and a control word repetition task to control for the motor output
      involved in response generation. RESULTS: Significant increases in local field
      potential Power (p <= 0.05) were seen across a broad gamma frequency band (30-95
      Hz) during both verbal fluency tasks, after controlling for motor output.
      Increases in gamma local field potential Power of +7.5% +/- 2.3% (SEM) in the
      semantic fluency task and +6.9% +/- 2.0% in the phonemic fluency task were
      derived when averaging across all electrode contact pairs. Gamma changes recorded
      from contacts lying in the left hemisphere (dominant in verbal fluency)
      correlated with average number of correct responses generated (r=0.81 p=0.015)
      and measures of 'switching' (r=0.79 p=0.020) particularly strongly in the
      semantic fluency task. INTERPRETATION: Frequency specific power changes observed
      during task performance are consistent with involvement of the subthalamic
      nucleus in switching during verbal fluency. Antagonism of such task-related
      activity with high frequency stimulation of this nucleus may explain the
      impairments reported.

PMID- 21872588
TI  - Effect of insulin and an erythropoietin-derived peptide (ARA290) on established
      neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse
      sympathetic ganglia.
AB  - The Akita mouse is a robust model of diabetic autonomic neuropathy which develops
      severe diabetes following beta cell death, which occurs reproducibly at 3-4 weeks
      of age, and maintains the diabetic state without therapy for as long as 11
      additional months. Neuritic dystrophy and neuronopathy involving prevertebral
      sympathetic superior mesenteric and celiac ganglia begin to develop within the
      first two months of onset of diabetes and are progressive with time. We have
      examined the effect of insulin implants resulting in normoglycemia and injections
      of ARA290, a small erythropoietin peptide which has no effect on glycemic
      parameters, on the reversal of established neuritic dystrophy and neuronopathy.
      We have found that 4 weeks of insulin therapy beginning at 2 months of diabetes
      resulted in normalization of blood glucose, body weight and HbA1c. Insulin
      therapy successfully reversed established neuritic dystrophy and neuronopathy to
      control levels. Numbers of sympathetic neurons were not significantly changed in
      either 3 month diabetic or insulin-treated Akita mice. Treatment with ARA290 for
      7 weeks beginning at 4 months of diabetes did not result in altered metabolic
      severity of diabetes as measured by blood glucose, body weight or HbA1c levels.
      ARA290 treatment was able to decrease neuritic dystrophy by 55-74% compared to
      untreated diabetics or in comparison to a separate group of diabetic animals
      representing the 4 month treatment onset point. Surprisingly, there was no effect
      of ARA290 on ganglionic neuron number or ongoing neuronopathy (pale/degenerating
      neurons) in diabetic Akita mice during this time period. The development of
      neuroprotective EPO-like peptides may provide a possible future therapy for this
      debilitating complication of diabetes; however, it appears that discrete elements
      may be differentially targeted by the diabetic state and may require selective
      therapy.

PMID- 21872590
TI  - MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target
      Sp1 in maintaining the chondrocyte proliferation.
AB  - MiR-140 is a microRNA specially involved in chondrogenesis and osteoarthritis
      pathogenesis. However, its transcriptional regulation and target genes in
      cartilage development are not fully understood. Here we detected that miR-140 was
      uniquely expressed in chondrocyte and suppressed by Wnt/beta-catenin signalling.
      The miR-140 primary transcript was an intron-retained RNA co-expressed with Wwp2
      C isoform, which was directly induced by Sox9 through binding to the intron 10 of
      Wwp2 gene. Knockdown of miR-140 in limb bud micromass cultures resulted in arrest
      of chondrogenic proliferation. Sp1, the activator of the cell cycle regulator
      p15(INK4b), was identified as a target of miR-140 in maintaining the chondrocyte
      proliferation. Collectively, our findings expand our understanding of the
      transcriptional regulation and the chondrogenic role of miR-140 in
      chondrogenesis.

PMID- 21872589
TI  - Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti
      oxidant and anti-atherosclerotic effects.
AB  - We have shown previously that insulin like-growth factor I (IGF-1) suppressed
      atherosclerosis in Apoe(-/-) mice and activated endothelial nitric oxide (NO)
      synthase. To determine whether IGF-1-induced atheroprotection depends on NO, IGF
      1- or saline-infused mice were treated with l-NAME, the pan-NO synthase inhibitor
      or with d-NAME (control). IGF-1 reduced atherosclerosis in both the d-NAME and l
      NAME groups suggesting that IGF-1's anti-atherogenic effect was NO-independent.
      IGF-1 increased plaque smooth muscle cells, suppressed cell apoptosis and
      downregulated lipoprotein lipase and these effects were also NO-independent. On
      the contrary, IGF-1 decreased oxidative stress and suppressed TNF-alpha levels
      and these effects were blocked by l-NAME. Thus IGF-1's anti-oxidant effect is
      dependent on its ability to increase NO but is distinct from its anti
      atherosclerotic effect which is NO-independent.

PMID- 21872591
TI  - miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion
      and apoptosis in colorectal cancer cells.
AB  - It has become increasingly clear that microRNAs play an important role in many
      human diseases including cancer. Here, we show that expression of miR-21 in
      HEK293 and several colorectal cancer cells was found inversely correlated with
      ras homolog gene family, member B (RhoB) expression. miR-21 expression
      significantly suppressed RhoB 3' UTR luciferase-reporter activity, but the
      inhibitory effect was lost when the putative target sites were mutated. Exogenous
      miR-21 over-expression mimicked the effect of RhoB knockdown in promoting
      proliferation and invasion and inhibiting apoptosis, whereas anti-miR-21 or RhoB
      expression yielded opposite effects, in colorectal cancer cells. These results
      suggest that miR-21 is a regulator of RhoB expression and RhoB could be a useful
      target in exploring the potential therapeutic benefits of miR-21 mediated tumor
      cell behaviors in colorectal cancer.

PMID- 21872592
TI  - Astrocytes contain amyloid-beta annular protofibrils in Alzheimer's disease
      brains.
AB  - Annular protofibrils (APFs) represent a newly described and distinct class of
      amyloid structures formed by disease-associated proteins. In vitro, these pore
      like structures have been implicated in membrane permeabilization and ion
      homeostasis via pore formation. Still, their formation and relevance in vivo are
      poorly understood. Herein, we report that APFs are in human Alzheimer's disease
      brain samples and that amyloid-beta APFs were associated with activated
      astrocytes. Moreover, we show that amyloid-beta APFs in astrocytes adopt a
      conformation in which the N-terminal region is buried inside the wall of the
      pore. Our results together with previous studies suggest that the formation of
      amyloid-beta APFs in astrocytes could be a relevant event in the pathogenesis of
      Alzheimer's disease and validate this amyloidogenic structure as a target for the
      prevention of the disease.

PMID- 21872593
TI  - Vaccinating against Helicobacter pylori: dissecting the mechanism.

PMID- 21872594
TI  - The control of iron homeostasis: microRNAS join the party.

PMID- 21872595
TI  - The KRAS p.G13D mutation in patients with metastatic colorectal cancer: a cheat
      in the orchestra of predictive biomarkers?

PMID- 21872596
TI  - Whole body cortisol and expression of HSP70, IGF-I and MSTN in early development
      of sea bass subjected to heat shock.
AB  - Whole body cortisol levels were determined during early larval developmental
      stages of sea bass (Dicentrarchus labrax) subjected to a heat shock with the aim
      to investigate the correlation between the stress event and the activation of the
      hypothalamic-pituitary-interrenal axis. Moreover, the mRNA expression of
      inducible heat shock protein 70 (HSP70), insulin-like growth factor I (IGF-I) and
      myostatin (MSTN) was also detected. Whole body cortisol was determined by a radio
      immunoassay (RIA) technique whereas the expression of HSP70, IGF-I and MSTN mRNAs
      was quantified by Real-Time PCR. Cortisol was detectable in all the larvae from
      hatching but its level increased significantly in larvae submitted to heat shock
      from 2-day post hatching onwards. An effect of the sole transfer on cortisol
      levels was detectable at day 10, indicating an increase of the hypothalamic
      pituitary-interrenal axis sensitivity from this stage of sea bass development. In
      animals exposed to heat shock, the expression of inducible HSP70 resulted in a
      marked increase of mRNA levels already at hatching. This increase was
      significantly higher from 6 days onwards if compared to controls. Moreover, heat
      shock resulted in a decrease (although not significant) in IGF-I mRNA expression
      of stressed larvae if compared to controls. On the contrary, heat shock did not
      influence the expression of MSTN mRNA in all groups. The results indicate a very
      early activation of the hypothalamic-pituitary-interrenal axis and in general of
      the stress response during the development of European sea bass. Moreover, these
      results suggest the importance of cortisol and inducible HSP70 as bioindicators
      of stress in aquaculture and confirm the role of IGF-I and MSTN as regulatory
      factors during development and growth of fish.

PMID- 21872597
TI  - Innate immunity and stress physiology of eastern hellbenders (Cryptobranchus
      alleganiensis) from two stream reaches with differing habitat quality.
AB  - In addition to depriving amphibians of physical habitat requirements (e.g.,
      shelter, moisture, and food), habitat modification may also have subtle effects
      on the health of amphibians and potentially precipitate interactions with other
      deleterious factors such as pathogens, contaminants, and invasive species. The
      current study was designed to evaluate the physiological state of imperiled giant
      salamanders, the eastern hellbender (Cryptobranchus alleganiensis), experiencing
      different surrounding land use that influences in-stream habitat quality. When we
      compared hellbenders from a stream reach with greater anthropogenic disturbance
      to a more forested site, we found that baseline and stress-induced plasma levels
      of corticosterone were similar in the two areas, but were very low compared to
      other amphibians. Males consistently had higher plasma corticosterone levels than
      females, a finding congruent with the known territorial activities of males early
      in the breeding season. Innate immune responsiveness (measured as bactericidal
      ability of blood; BKA) was also similar at the two sites, but juveniles had less
      robust BKA than adults. We found a positive relationship between restraint time
      and BKA, suggesting that the bactericidal ability of hellbenders may improve
      following acute stress. Finally, there was a tendency for hellbenders with skin
      abnormalities to have higher BKA compared to individuals with normal integument,
      an observation consistent with patterns observed in other animals actively
      responding to pathogens. Our study provides foundational physiological
      information on an imperiled amphibian species and reveals important knowledge
      gaps that will be important for understanding the ecology, evolution, and
      conservation of hellbenders.

PMID- 21872598
TI  - Orphanin FQ in the mediobasal hypothalamus facilitates sexual receptivity through
      the deactivation of medial preoptic nucleus mu-opioid receptors.
AB  - Sexual receptivity, lordosis, can be induced by sequential estradiol and
      progesterone or extended exposure to high levels of estradiol in the female rat.
      In both cases estradiol initially inhibits lordosis through activation of beta
      endorphin (beta-END) neurons of the arcuate nucleus of the hypothalamus (ARH)
      that activate MU-opioid receptors (MOP) in the medial preoptic nucleus (MPN).
      Subsequent progesterone or extended estradiol exposure deactivates MPN MOP to
      facilitate lordosis. Opioid receptor-like receptor-1 (ORL-1) is expressed in ARH
      and ventromedial hypothalamus (VMH). Infusions of its endogenous ligand, orphanin
      FQ (OFQ/N, aka nociceptin), into VMH-ARH region facilitate lordosis. Whether
      OFQ/N acts in ARH and/or VMH and whether OFQ/N is necessary for steroid
      facilitation of lordosis are unclear. In Exp I, OFQ/N infusions in VMH and ARH
      that facilitated lordosis also deactivated MPN MOP indicating that OFQ/N
      facilitation of lordosis requires deactivation of ascending ARH-MPN projections
      by directly inhibiting ARH beta-END neurons and/or through inhibition of
      excitatory VMH-ARH pathways to proopiomelanocortin neurons. It is unclear whether
      OFQ/N activates the VMH output motor pathways directly or via the deactivation of
      MPN MOP. In Exp II we tested whether ORL-1 activation is necessary for estradiol
      only or estradiol+progesterone lordosis facilitation. Blocking ORL-1 with UFP-101
      inhibited estradiol-only lordosis and MPN MOP deactivation but had no effect on
      estradiol+progesterone facilitation of lordosis and MOP deactivation. In
      conclusion, steroid facilitation of lordosis inhibits ARH beta-END neurons to
      deactivate MPN MOP, but estradiol-only and estradiol+progesterone treatments
      appear to use different neurotransmitter systems to inhibit ARH-MPN signaling.

PMID- 21872600
TI  - Within seasons and among years: when are corticosterone levels repeatable?
AB  - Hormones play a central role in integrating internal and external cues to help
      mediate life-history decisions as well as changes in behavior and physiology of
      individuals. Describing the consistency of endocrine traits within and among
      individuals is an important step for understanding whether hormonal traits are
      dependable predictors of phenotypes that selection could act upon. However, few
      long-term field studies have investigated the individual consistency of hormonal
      traits. Glucocorticoid hormones mediate homeostatic responses to environmental
      variation as well as stress responses to acute, unpredictable disturbances. We
      characterized the repeatability of plasma corticosterone concentrations in two
      species of free-living passerines across multiple years. We found repeatability
      in baseline corticosterone concentrations in both sexes of great tits (Parus
      major) and in female tree swallows (Tachycineta bicolor) within the breeding
      season but no repeatability of this trait among seasons or across years. Stress
      induced levels of corticosterone were only assessed in great tits and were not
      repeatable in either sex. Our data suggest that in line with their function in
      mediating responses of individuals to longer-term and acute demands, both
      baseline and stress-induced plasma corticosterone concentrations are rather
      plastic traits. However, individuals may differ in their degree of trait
      plasticity and hence in behavioral and physiological responses to a variety of
      organismal challenges.

PMID- 21872599
TI  - Oxytocin mediates the acquisition of filial, odor-guided huddling for maternally
      associated odor in preweanling rats.
AB  - The present study was designed to examine possible roles of oxytocin (OT) in the
      acquisition of a filial huddling preference in preweanling rats. We used a
      procedure in which a scented, foster mother can induce an odor-guided huddling
      preference in preweanling pups, following a single, 2-h-long co-habitation
      (Kojima and Alberts, 2009, 2011). This single, discrete period for preference
      learning enables us to observe the mother-pup interactions that establish the
      pups' preferences and to intervene with experimental manipulations. Four, 14-day
      old littermates interacted with a scented foster mother that provided maternal
      care during a 2-h session. Two of the pups were pretreated with an
      intracerebroventricular injection of OT or an oxytocin antagonist (OTA), and the
      others received a vehicle injection. Filial preference for a maternally-paired
      odor was measured in a huddling test the next day. OT is necessary for
      acquisition of the filial preference: The preference learning was blocked in the
      pups treated with OTA, but not in their vehicle-treated littermates who
      experienced the same mother at the same time. Injection with exogenous OT did not
      augment the pups' preference. Manipulating pups' central OT also altered the
      contact interactions of the mother and pups. When some pups received OT, mother
      litter aggregations formed as frequently and with similar combinations of bodies,
      but contact aggregations were significantly more cohesive than when some pups in
      the litter received OTA. We discuss dual, behavioral and neuroendocrine roles of
      OT in social learning by preweanling rats.

PMID- 21872601
TI  - Motivation to obtain preferred foods is enhanced by ghrelin in the ventral
      tegmental area.
AB  - Ghrelin is an orexigenic peptide that acts within the central nervous system to
      stimulate appetite and food intake via the growth hormone secretagogue receptor
      (GHS-R). It has been hypothesized that ghrelin modulates food intake in part by
      stimulating reward pathways in the brain and potentially stimulating the intake
      of palatable foods. Here we examined the effects of chronic ghrelin
      administration in the ventral tegmental area (VTA) via osmotic minipumps on 1) ad
      libitum food intake and bodyweight; 2) macronutrient preference; and 3)
      motivation to obtain chocolate pellets. In the first study rats receiving ghrelin
      into the VTA showed a dose-dependent increase in the intake of regular chow, also
      resulting in increased body weight gain. A second study revealed that intra-VTA
      delivery of the ghrelin receptor antagonist [Lys-3]-GHRP-6 selectively reduced
      caloric intake of high-fat chow and reduced body weight gain relative to control
      and ghrelin treated rats. The third study demonstrated that food restricted rats
      worked harder for food pellets when infused with ghrelin than when infused with
      vehicle or ghrelin receptor antagonist treated rats. Finally, rats trained on an
      FR1 schedule but returned to ad libitum during ghrelin infusion, responded at 86%
      of baseline levels when they were not hungry, whereas saline infused rats
      responded at 36% of baseline. Together, these results suggest that ghrelin acts
      directly on the VTA to increase preference for and motivation to obtain highly
      palatable food.

PMID- 21872602
TI  - Simulating winning in the wild--the behavioral and hormonal response of black
      redstarts to single and repeated territorial challenges of high and low
      intensity.
AB  - In many vertebrates testosterone increases during aggressive interactions and the
      surges in this hormone may be responsible for the winner effect. So far studies
      on this relationship have been done in captivity only, because simulating a
      winning situation for a territory owner in the field is difficult. However, an
      increasing number of studies show that territorial aggression is not necessarily
      accompanied by elevated testosterone after a single simulated territorial
      intrusion (STI) and therefore it has been proposed that STIs may even create a
      losing experience. We examined whether free-living male black redstarts
      (Phoenicurus ochruros) show changes in androgens, corticosterone and behavior
      following repeated STIs of high or low intensity and in contrast to being
      challenged only once. Repeated intrusions had no influence on androgen and
      corticosterone levels regardless of intrusion intensity. In contrast, the
      behavioral response changed over days depending on the intensity of the
      intrusion. Only birds challenged with high-level intruders approached the decoy
      significantly faster during the third intrusion than during the first one, stayed
      closer to the decoy, and sang more songs than males challenged with low-level
      intruders. Thus, although black redstarts reacted differently to STIs varying in
      frequency and intensity, these behavioral differences were not reflected in
      androgen or corticosterone levels. Our data show that it is unlikely that STIs
      induce a losing experience. Furthermore, they indicate that a hormonal effect of
      winning an encounter may not be universal in vertebrates and may depend on the
      ecological or life-history context.

PMID- 21872604
TI  - Rapid cold hardening increases cold and chilling tolerances more than acclimation
      in the adults of the sycamore lace bug, Corythucha ciliata (Say) (Hemiptera:
      Tingidae).
AB  - The sycamore lace bug, Corythucha ciliata is a new, invasive pest of Platanus
      trees in China. Although C. ciliata is often subjected to acute low temperatures
      in early winter and spring in northern and eastern China, the cold tolerance of
      C. ciliata has not been well studied. The objectives of this study were to
      determine whether adults of C. ciliata are capable of rapid cold hardening (RCH),
      and to compare the benefits of RCH vs. cold acclimation (ACC) in the laboratory.
      When the adult females incubated at 26 degrees C were transferred directly to the
      discriminating temperature (-12 degrees C) for 2 h, survival was only 22%.
      However, exposure to 0 degrees C for 4 h before transfer to -12 degrees C for 2 h
      induced RCH, i.e., increased survival to 68%. RCH could also be induced by
      gradual cooling of the insects at rates between 0.1 and 0.25 degrees C min(-1).
      The protection against cold shock obtained through RCH at 0 degrees C for 4 h was
      lost within 1h if the adults were returned to 26 degrees C before exposure to -12
      degrees C. Survival at both -12 and -5 degrees C was greater for RCH-treated than
      for ACC-treated adults (for ACC, adults were kept at 15 degrees C for 5 days),
      and the lethal temperature (2 h exposure) was lower for RCH-treated than for ACC
      treated adults. The results suggest that RCH may help C. ciliata survive the
      acute low temperatures that often occur in early winter and early spring in
      northern and eastern China.

PMID- 21872606
TI  - The effect of spatially correlated environments on genetic diversity-area
      relationships.
AB  - Understanding the spatial patterns of genetic diversity and what causes them is
      an important outstanding question in ecology. Here we investigate the roles of
      spatial heterogeneity and system area in generating genome diversity, and study
      its dependence with sampled area. We study an individual-based model that
      incorporates natural selection on the habitat type and compare the effects of
      asexual and sexual reproductions. A key ingredient of the model is the
      possibility to tune the level of spatial heterogeneity among the habitats. Our
      results corroborate either the bi-phasic or tri-phasic scenarios, one phase
      corresponding to a power law regime, for the diversity-area relationship in both
      sexual and asexual populations, being the shape of the curve influenced by
      mutation rates and spatial correlation. These observations are verified for
      distinct sets of parameter values.

PMID- 21872605
TI  - Symerythrin structures at atomic resolution and the origins of rubrerythrins and
      the ferritin-like superfamily.
AB  - Rubrerythrins are diiron-containing peroxidases that belong to the ferritin-like
      superfamily (FLSF). Here, we describe the structures of symerythrin, a novel
      rubrerythrin variant from the oxygenic phototroph Cyanophora paradoxa, at 1.20
      1.40 A resolution in three different states: diferric, azide-bound diferric and
      chemically reduced. The symerythrin metallocenter has a unique eighth ligating
      residue compared to rubrerythrin-an additional glutamate inserted into helix A of
      the four-helix bundle that resides on a pi-helical segment. Otherwise, the
      diferric metallocenter structure is highly similar to that of characterized
      rubrerythrins. Azide binds the diferric center in a MU-1,1 orientation similar to
      how peroxide binds to diferric rubrerythrin. The structure of the diferrous
      metallocenter shows heterogeneity that we ascribe to the acidic pH of the
      crystals. In what we consider the neutral pH conformation, reduction causes a 2.0
      A shift in Fe1 and the toggling of a Glu to a His ligand, as seen with
      rubrerythrins. The function of symerythrin remains unknown, but preliminary tests
      showing oxidase and peroxidase activities and the similarities of its
      metallocenter to other rubrerythrins suggest similar functionalities between the
      two despite the additional ligating glutamate in symerythrin. Of particular
      interest is the high internal symmetry of symerythrin, which supports the notion
      that its core four-helix bundle was formed by the gene duplication and fusion of
      a two-helix peptide. Sequence comparisons with another family in the FLSF that
      also has notable internal symmetry provide compelling evidence that, contrary to
      previous assumptions, there have been multiple gene fusion events that have
      generated the single-chain FLSF fold.

PMID- 21872603
TI  - A broadly applicable approach to T cell epitope identification: application to
      improving tumor associated epitopes and identifying epitopes in complex
      pathogens.
AB  - Epitopes are a hallmark of the antigen specific immune response. The
      identification and characterization of epitopes is essential for modern
      immunologic studies, from investigating cellular responses against tumors to
      understanding host/pathogen interactions especially in the case of bacteria with
      intracellular residence. Here, we have utilized a novel approach to identify T
      cell epitopes exploiting the exquisite ability of particulate antigens, in the
      form of beads, to deliver exogenous antigen to both MHC class I and class II
      pathways for presentation to T cell hybridomas. In the current study, we coupled
      this functional assay with two distinct protein expression libraries to develop a
      methodology for the characterization of T cell epitopes. One set of expression
      libraries containing single amino acid substitutions in a defined epitope
      sequence was interrogated to identify epitopes with enhanced T cell stimulation
      for a MHC class I epitope. The second expression library is comprised of the
      majority of open reading frames from the intracellular pathogen and potential
      biowarfare agent, Francisella tularensis. By automating aspects of this
      technology, we have been able to functionally screen and identify novel T cell
      epitopes within F. tularensis. We have also expanded upon these studies to
      generate a novel expression vector that enables immunization of recombinant
      protein into mice, which has been utilized to facilitate T cell epitope discovery
      for proteins that are critically linked to Francisella pathogenicity. This
      methodology should be applicable to a variety of systems and other pathogens.

PMID- 21872607
TI  - Regulatory patterns in molecular interaction networks.
AB  - Understanding design principles of molecular interaction networks is an important
      goal of molecular systems biology. Some insights have been gained into features
      of their network topology through the discovery of graph theoretic patterns that
      constrain network dynamics. This paper contributes to the identification of
      patterns in the mechanisms that govern network dynamics. The control of nodes in
      gene regulatory, signaling, and metabolic networks is governed by a variety of
      biochemical mechanisms, with inputs from other network nodes that act additively
      or synergistically. This paper focuses on a certain type of logical rule that
      appears frequently as a regulatory pattern. Within the context of the multistate
      discrete model paradigm, a rule type is introduced that reduces to the concept of
      nested canalyzing function in the Boolean network case. It is shown that networks
      that employ this type of multivalued logic exhibit more robust dynamics than
      random networks, with few attractors and short limit cycles. It is also shown
      that the majority of regulatory functions in many published models of gene
      regulatory and signaling networks are nested canalyzing.

PMID- 21872608
TI  - Beneficial effects of human altruism.
AB  - In this work we review converging evidence from several lines of research which
      suggests that altruism in humans can be intrinsically rewarding. Various
      investigations illustrate how human altruism can have beneficial effects on
      health and wellbeing. In this contribution we propose a model that includes
      positive effects of altruism. These beneficial effects lead to significant
      changes in the dynamics of the system, favouring higher levels of altruism and
      facilitating abrupt changes towards cooperation. In the present model, social
      modulation occurs at both individual and collective levels. The potential
      beneficial role of altruism proposed here may account for its occurrence among
      non-kin and beyond reciprocity.

PMID- 21872609
TI  - Analysis of the interaction of the Eg5 Loop5 with the nucleotide site.
AB  - Loop 5 (L5) is a conserved loop that projects from the alpha2-helix adjacent to
      the nucleotide site of all kinesin-family motors. L5 is critical to the function
      of the mitotic kinesin-5 family motors and is the binding site for several
      kinesin-5 inhibitors that are currently in clinical trials. Its conformational
      dynamics and its role in motor function are not fully understood. Our previous
      work using EPR spectroscopy suggested that L5 alters the nucleotide pocket
      conformation of the kinesin-5 motor Eg5 (Larson et al., 2010). EPR spectra of a
      spin-labeled nucleotide analog bound at the nucleotide site of Eg5 display a
      highly immobilized component that is absent if L5 is shortened or if the
      inhibitor STLC is added (Larson et al., 2010), which X-ray structures suggest
      stabilizes an L5 conformation pointing away from the nucleotide site. These data,
      coupled with the proximity of L5 to the nucleotide site suggest L5 could interact
      with a bound nucleotide, modulating function. Here we use molecular dynamics (MD)
      simulations of Eg5 to explore the interaction of L5 with the nucleotide site in
      greater detail. We performed MD simulations in which the L5-domain of the Eg5.ADP
      X-ray structure was manually deformed via backbone bond rotations. The L5-domain
      of Eg5 was sufficiently lengthy that portions of L5 could be located in proximity
      to bound ADP. The MD simulations evolved to thermodynamically stable structures
      at 300 K showing that L5 can interact directly with bound nucleotide with
      significant impingement on the ribose hydroxyls, consistent with the EPR
      spectroscopy results. Taken together, these data provide support for the
      hypothesis that L5 modulates Eg5 function via interaction with the nucleotide
      binding site.

PMID- 21872610
TI  - Parathyroid hormone-related protein and glucocorticoid receptor beta are
      regulated by cortisol in the kidney of male mice.
AB  - AIMS: Parathyroid hormone-related protein (PTHrP) is a peptide growth factor
      produced in a wide range of tissues from brain and parathyroid, to kidney and
      uterus. The purpose of this study was to determine whether the adrenal cortical
      hormones, hydrocortisone (cortisol), modulate PTHrP expression and glucocorticoid
      receptor (GR)beta in mice kidney. MAIN METHODS: Changes in PTHrP gene expression
      were determined by real-time PCR and its protein level was examined by Western
      blot analysis. In addition, expression of renal PTHrP protein was localized by
      immunohistochemistry. Effects of RU486 on the expression levels of GRalpha/beta
      or PTHrP gene in the kidneys were analyzed by Western blot analysis. KEY
      FINDINGS: We found that renal expression levels of PTHrP mRNA were higher in
      males than in females up to 9weeks of age. Using immunohistochemistry, we
      observed higher levels of PTHrP expression within the cortex than in the medulla
      in both male and female mice, and this expression was localized in the epithelial
      cells of the renal proximal tubules. Treatment of 4-week-old mice with
      aldosterone and cortisol for three days showed larger increases in both PTHrP
      mRNA and protein levels in males compared with females. The expression of GRbeta
      in male, but not female, kidneys was significantly upregulated after treatment
      with cortisol, but not after treatment with aldosterone. Inhibition of
      glucocorticoid signaling by pre-treatment with a GR antagonist prior to cortisol
      administration largely abolished this cortisol-dependent increase in PTHrP and
      GRbeta expressions. SIGNIFICANCE: These results suggest that PTHrP expression and
      GRbeta in the kidneys of male mice may be regulated by cortisol.

PMID- 21872611
TI  - Absence of equilibrative nucleoside transporter 1 in ENT1 knockout mice leads to
      altered nucleoside levels following hypoxic challenge.
AB  - AIMS: Equilibrative nucleoside transporters (ENT) modulate the flux of adenosine.
      The ENT1-null (KO) mouse heart is endogenously cardioprotected but the cellular
      basis of this phenotype is unknown. Therefore, we investigated the cellular
      mechanisms underlying ENT1-mediated cardioprotection. MAIN METHODS: Circulating
      adenosine levels were measured in WT and KO mice. Cellular levels of nucleosides
      and nucleotides were investigated in isolated adult cardiomyocytes from WT and KO
      mice using HPLC following hypoxic challenge (30 min, 2% O(2)). Changes in hypoxic
      gene expression were analyzed by PCR arrays and cAMP levels were measured to
      investigate contributions from adenosine receptors. KEY FINDINGS: Circulating
      adenosine levels were significantly higher in KO (416+/-42nmol/l, n=12) compared
      to WT animals (208+/-21, n=13, p<0.001). Absence of ENT1 led to an elevated
      expression of genes involved in cardioprotective pathways compared to WT
      cardiomyocytes. Following hypoxic challenge, extracellular adenosine levels were
      significantly elevated in KO (4360+/-1840 pmol/mg protein) versus WT
      cardiomyocytes (3035+/-730 pmol/mg protein, n>=12, p<0.05). This effect was
      enhanced in the presence of dipyridamole (30 MUM), which inhibits ENT1 and ENT2.
      Enhanced extracellular adenosine levels in ENT1-null cardiomyocytes appeared to
      come from a pool of extracellular nucleotides including IMP, AMP and ADP.
      Adenosine receptor (AR) activation mimicked increases in cAMP levels due to
      hypoxic challenge suggesting that ENT1 modulates AR-dependent signaling.
      SIGNIFICANCE: ENT1 contributes to modulation of extracellular adenosine levels
      and subsequent purinergic signaling via ARs. ENT1-null mice possess elevated
      circulating adenosine levels and reduced cellular uptake resulting in a
      perpetually cardioprotected phenotype.

PMID- 21872612
TI  - Combination of TS-021 with metformin improves hyperglycemia and synergistically
      increases pancreatic beta-cell mass in a mouse model of type 2 diabetes.
AB  - AIMS: The objectives of this study were to elucidate the effects of a potent
      dipeptidyl peptidase (DPP)-IV inhibitor, TS-021, combined with/without metformin
      on glycemic control and pathological changes in pancreatic islets in high-fat
      diet and streptozotocin-induced (HFD-STZ) diabetic mice. MAIN METHODS: The anti
      diabetic effects of TS-021 and/or metformin in HFD-STZ mice were examined in both
      acute and chronic treatment studies. In addition, we performed
      immunohistochemical analysis after repeated administration of TS-021 and/or
      metformin to HFD-STZ mice twice a day for 5 weeks. KEY FINDINGS: In the acute
      treatment study, TS-021 and/or metformin significantly improved glucose tolerance
      and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination
      with metformin significantly increased the plasma insulin level after nutrient
      ingestion. In the chronic treatment study, TS-021 in combination with metformin
      significantly lowered the glycosylated hemoglobin level, plasma insulin level,
      and alpha-cell-to-beta-cell area ratio in pancreatic islets. In particular, the
      combined treatment synergistically increased the insulin-positive area in
      pancreatic islets from 32.3% in diabetic mice treated with the vehicle to 51.1%
      (TS-021 alone, 35.3%; metformin alone, 30.6%). SIGNIFICANCE: The present study
      demonstrated that the coadministration of TS-021 and metformin synergistically
      improved the islet morphology by increasing the circulating level of biologically
      active GLP-1, which is thought to result from two different mechanisms (namely,
      an increase in GLP-1 secretion and DPP-IV inhibition). These findings strongly
      support the rationale for combined treatment with DPP-IV inhibitors plus
      metformin in clinical practice by clearly demonstrating an anti-diabetic effect
      associated with the remarkable improvement in pancreatic beta-cell morphology.

PMID- 21872613
TI  - Lasting first impressions: a conservative bias in automatic filters of the
      acoustic environment.
AB  - Even in the unattended auditory environment, what we learn first appears
      resistant to re-evaluation based on experience. Mismatch negativity (MMN) is an
      auditory event-related potential elicited to rare deviation from automatically
      generated predictions about the sound environment. MMN amplitude is thought to
      reflect the potential importance of a sound for further processing. This study
      was designed to explore the degree to which past experience with a sound can
      alter automatic attributions about that sound's importance. MMN was elicited to
      rare (p=.125) physical "deviants" amongst a sequence of highly probable (p=.875)
      "standard" sounds. Sound identity alternated across blocks within the sequence
      (i.e., the former deviant became the new standard and the former standard the new
      deviant). The time period over which a standard remained the more probable tone
      was varied over Fast (0.8 min), Medium (1.6 min) and Slow (2.4 min) change
      conditions. Given that local within-block probabilities remained constant across
      conditions, any change in MMN size was considered a reflection of more rostral
      brain regions enabling a longer time scale (across-block) representation of event
      probability extraction. Larger MMNs were expected to deviations in blocks with
      longer standard-stability. Although a significant increase in MMN amplitude was
      observed with increased rule stability, MMN amplitude was heavily dependent on
      the initial sequence structure. A "primacy bias" was observed such that prolonged
      stability produced large increases in the MMN to deviations from the first
      established standard but substantially smaller MMN to this first standard as a
      later deviant. The primacy effect in these data implies that the automatic
      filtering of sound relevance is biased toward a confirmation of initial
      expectations. Initial experience therefore altered the perceived salience of
      subsequent events.

PMID- 21872614
TI  - The "paradoxical" engagement of the primary auditory cortex in patients with
      auditory verbal hallucinations: a meta-analysis of functional neuroimaging
      studies.
AB  - The existing literature on neuroimaging studies of auditory verbal hallucinations
      (AVHs) in patients with schizophrenia contains an apparent "paradox" in that the
      same areas in the auditory cortex seem to be both activated and deactivated in
      relation to AVHs, depending on whether an external auditory stimulus is present
      or not. We performed meta-analyses of neuroimaging studies examining patients
      with schizophrenia during the processing of auditory stimuli and in individuals
      experiencing hallucinations in the absence of auditory stimuli to examine whether
      the auditory cortex shows the paradoxical decrease/increase pattern across
      studies. Databases PubMed and ISI Web of Knowledge were queried with the
      combination of the keywords "auditory verbal hallucinations", "auditory
      hallucinations", "fMRI", "PET", "imaging", yielding 11 studies involving
      comparison between schizophrenia and control group during external auditory
      stimulation, and 12 studies of hallucinating subjects experiencing AVHs and
      resting in the absence of auditory stimulation. The data were analyzed using
      Activation Likelihood Estimation method. The results showed overlapping increased
      activation in the absence of an external stimulus, and decreased activation in
      the presence of an external auditory stimulus in the left primary auditory cortex
      and in the right rostral prefrontal cortex, confirming the "paradoxical" brain
      activation in relation to AVHs. It is suggested that the "paradox" may be caused
      by an attentional bias towards internally generated information and failure of
      down- and up-regulation of the default mode and auditory processing networks,
      respectively, with the consequence that the spontaneous activation in the absence
      of an external stimulus shuts down the perceptual apparatus for further
      processing.

PMID- 21872615
TI  - Stereospecific synthesis of new steroidal isoxazoles in dry media.
AB  - An easy and fast procedure was developed for one-pot synthesis of steroidal
      isoxazoles starting from 23-acetylsapogenins derivatives in presence of P2O5/SiO2
      in dry media under microwaves irradiation is described. Substrates of the 25S and
      25R series were used as raw materials, establishing that this new methodology is
      applicable to both series.

PMID- 21872616
TI  - Synthesis of 2-substituted 17beta-hydroxy/17-methylene estratrienes and their in
      vitro cytotoxicity in human cancer cell cultures.
AB  - Synthesis of various types of 2-(alkylaminomethyl) and 2-(aroyl) 17beta-estradiol
      analogs are reported. The synthesis of similar types of 2-substituted 17
      methylene estratriene analogs was also achieved. Synthesis of chalcone
      derivatives of 17beta-estradiol and 17-methylene estratriene were also realized.
      All these 2-substituted estratrienes were tested for their antiproliferative
      activity by using four different cell lines from colon, lung, glioma and breast
      cancers. Among the various 2-substituted estratrienes, the compounds 10d, 14a-h
      and 17e were found to have in vitro antiproliferative activity comparable to that
      of parent analogs 1-4. Comparison of the SAR pattern of these 2-susbtituted
      estratriene derivatives confirmed that relatively, 17-methylene estratrienes are
      more active than that of 17beta-estradiol analogs.

PMID- 21872617
TI  - Determination of the non protein amino acid beta-N-methylamino-l-alanine in
      estuarine cyanobacteria by capillary electrophoresis.
AB  - A capillary electrophoretic method for the determination of the amino acid beta-N
      methylamino-l-alanine (BMAA) was achieved using a fused-silica capillary column
      (50 cm * 75 MUm I.D.) filled with 5 mM sodium tetraborate solution (pH 9), with
      an applied voltage of 25 kV, at 25  degrees C. The method was then applied in
      quantifying BMAA in eighteen strains of lyophilized estuarine cyanobacteria,
      following amino acid extraction using 0.1 M trichloroacetic acid and 6 M
      hydrochloric acid, sequentially.

PMID- 21872618
TI  - In memoriam: Costas Drainas (1950-2011).

PMID- 21872619
TI  - The basic emotional circuits of mammalian brains: do animals have affective
      lives?
AB  - The primal affects are intrinsic brain value systems that unconditionally and
      automatically inform animals how they are faring in survival. They serve an
      essential function in emotional learning. The positive affects index "comfort
      zones" that support survival, while negative affects inform animals of
      circumstances that may impair survival. Affective feelings come in several
      varieties, including sensory, homeostatic, and emotional (which I focus on here).
      Primary-process emotional feelings arise from ancient caudal and medial
      subcortical regions, and were among the first subjective experiences to exist on
      the face of the earth. Without them, higher forms of conscious "awareness" may
      not have emerged in primate brain evolution. Because of homologous "instinctual"
      neural infrastructures, we can utilize animal brain research to reveal the nature
      of primary-process human affects. Since all vertebrates appear to have some
      capacity for primal affective feelings, the implications for animal-welfare and
      how we ethically treat other animals are vast.

PMID- 21872620
TI  - A culture model for neurite regeneration of human spinal cord neurons.
AB  - Effective therapeutic interventions for injuries of the central nervous system
      such as spinal cord injury are still unavailable, having a great impact on the
      quality of life of victims and their families, as well as high costs in medical
      care. Animal models of spinal cord injury are costly, time-consuming and labor
      intensive, making them unsuitable for screening large numbers of experimental
      conditions. Thus, culture models that recapitulate key aspects of neuronal
      changes in central nervous system injuries are needed to gain further
      understanding of the pathological and regenerative mechanisms involved, as well
      as to accelerate the screening of potential therapeutic agents. In this study we
      differentiated adherent cultures of dissociated human fetal spinal cord neural
      precursors into postmitotic neurons which we could then detach from culture
      plates and successfully freeze down in a viable state. When replated in neuronal
      medium without neurodifferentiating factors, these ready-to-use human spinal cord
      neurons remained viable, postmitotic and regenerated neurites in a cell density
      dependent manner. Insulin-like growth factor 1 and growth hormone had no effect
      on neurite regeneration while brain-derived neurotrophic factor increased both
      the number of cells with neurites as well as the average neurite length. Our
      model can be applied to investigate factors involved in neuroregeneration of the
      human spinal cord and since adherent dissociated cell cultures are used, this
      system has significant potential as a screening platform for therapeutic agents
      to treat spinal cord injury.

PMID- 21872621
TI  - Evaluation study of a portable impedance biosensor for detection of avian
      influenza virus.
AB  - Current methods for detection of avian influenza virus (AIV) based on virus
      culture and RT-PCR are well established, but they are either time consuming or
      require specialized laboratory facilities and highly trained technicians. A
      simple, rapid, robust, and reliable test, suitable for use in the field or at the
      patient's bedside, is urgently needed. In this study, the performance of a newly
      developed portable impedance biosensor was evaluated by comparison with real-time
      reverse transcriptase PCR (rRT-PCR) and virus culture for detection of AIV in
      tracheal and cloacal swab samples collected from experimentally H5N2 AIV infected
      chickens. The impedance biosensor system was based on a combination of magnetic
      nanobeads, which were coated with AIV subtype-specific antibody for capture
      (separation and concentration) of a target virus, and a microfluidic chip with an
      interdigitated array microelectrode for transfer and detection of target virus,
      and impedance measurement of the bio-nanobeads and AI virus complexes in a buffer
      solution. A comparison of results obtained from 59 swab samples using virus
      culture, impedance biosensor and rRT-PCR methods showed that the impedance
      biosensor technique was comparable in sensitivity and specificity to rRT-PCR.
      Detection time for the impedance biosensor is less than 1h.

PMID- 21872623
TI  - Sigh rate and respiratory variability during normal breathing and the role of
      negative affectivity.
AB  - Spontaneous breathing was measured in healthy persons scoring either high (N=45)
      or low (N=30) on trait negative affectivity (NA), during a 10 min period of quiet
      sitting using the LifeShirt System(r). Sighing and respiratory variability before
      and after sighs were assessed. Total respiratory variability of minute
      ventilation was indexed by the coefficient of variation and structured
      (correlated) variability was quantified by the autocorrelation. Total variability
      was higher before a sigh than before a non-sigh, without concomitant differences
      in structured variability, suggesting more random variability before a sigh.
      After a sigh, correlated variability increased whereas it remained the same after
      a non-sigh. Thus sighing acted as a resetter of the respiratory system. However,
      when comparing the low and the high NA group, this pattern was specific for high
      NA individuals. We conclude that it is important to take into account individual
      difference variables when studying the psychophysiological functions of sighing.

PMID- 21872622
TI  - Acid phosphatase test proves superior to standard phenotypic identification
      procedure for Clostridium perfringens strains isolated from water.
AB  - Clostridium perfringens is used as an indicator for persistent faecal pollution
      as well as to monitor the efficacy of water treatment processes. For these
      purposes, differentiation between C. perfringens and other Clostridia is
      essential and is routinely carried out by phenotypic standard tests as proposed
      in the ISO/CD 6461-2:2002 (ISO_LGMN: lactose fermentation, gelatine liquidation,
      motility and nitrate reduction). Because the ISO_LGMN procedure is time consuming
      and labour intensive, the acid phosphatase test was investigated as a possible
      and much more rapid alternative method for confirmation. The aim of our study was
      to evaluate and compare confirmation results obtained by these two phenotypic
      methods using genotypically identified strains, what to our knowledge has not
      been accomplished before. For this purpose, a species specific PCR method was
      selected based on the results received for type strains and genotypically
      characterised environmental strains. For the comparative investigation type
      strains as well as presumptive C. perfringens isolates from water and faeces
      samples were used. The acid phosphatase test revealed higher percentage (92%) of
      correctly identified environmental strains (n=127) than the ISO_LGMN procedure
      (83%) and proved to be a sensitive and reliable confirmation method.

PMID- 21872624
TI  - Transport of drugs across the blood-brain barrier by nanoparticles.
AB  - The central nervous system is well protected by the blood-brain barrier (BBB)
      which maintains its homeostasis. Due to this barrier many potential drugs for the
      treatment of diseases of the central nervous system (CNS) cannot reach the brain
      in sufficient concentrations. One possibility to deliver drugs to the CNS is the
      employment of polymeric nanoparticles. The ability of these carriers to overcome
      the BBB and to produce biologic effects on the CNS was shown in a number of
      studies. Over the past few years, progress in understanding of the mechanism of
      the nanoparticle uptake into the brain was made. This mechanism appears to be
      receptor-mediated endocytosis in brain capillary endothelial cells. Modification
      of the nanoparticle surface with covalently attached targeting ligands or by
      coating with certain surfactants enabling the adsorption of specific plasma
      proteins are necessary for this receptor-mediated uptake. The delivery of drugs,
      which usually are not able to cross the BBB, into the brain was confirmed by the
      biodistribution studies and pharmacological assays in rodents. Furthermore, the
      presence of nanoparticles in the brain parenchyma was visualized by electron
      microscopy. The intravenously administered biodegradable polymeric nanoparticles
      loaded with doxorubicin were successfully used for the treatment of experimental
      glioblastoma. These data, together with the possibility to employ nanoparticles
      for delivery of proteins and other macromolecules across the BBB, suggest that
      this technology holds great promise for non-invasive therapy of the CNS diseases.

PMID- 21872625
TI  - Biological properties of prolactin-releasing peptide analogs with a modified
      aromatic ring of a C-terminal phenylalanine amide.
AB  - Prolactin-releasing peptide (PrRP)-induced secretion of prolactin is not
      currently considered a primary function of PrRP, but the development of late
      onset obesity in both PrRP and PrRP receptor knock-out mice indicates the unique
      anorexigenic properties of PrRP. In our recent study, we showed comparable
      potencies of peptides PrRP31 and PrRP20 in binding, intracellular signaling and
      prolactin release in pituitary RC-4B/C cells, and anorexigenic effect after
      central administration in fasted mice. In the present study, eight analogs of
      PrRP20 with C-terminal Phe amide modified with a bulky side chain or a
      halogenated aromatic ring revealed high binding potency, activation of mitogen
      activated protein kinase/extracellular-regulated kinase (MAPK/ERK1/2) and cAMP
      response element-binding protein (CREB) and prolactin release in RC-4B/C cells.
      In particular, [PheNO(2)(31)]PrRP20, [1-Nal(31)]PrRP20, [2-Nal(31)]PrRP20 and
      [Tyr(31)]PrRP20 showed not only in vitro effects comparable or higher than those
      of PrRP20, but also a very significant and long-lasting anorexigenic effect after
      central administration in fasted mice. The design of potent and long-lasting PrRP
      analogs with selective anorexigenic properties promises to contribute to the
      study of food intake disorders.

PMID- 21872626
TI  - Mismatches outside exons 2 and 3 do not alter the peptide motif of the allele
      group B*44:02P.
AB  - Sequence variations outside exons 2 and 3 do not appear to affect the function of
      human leukocyte antigen (HLA) class I alleles. HLA-B*44:02:01:01 and -B*44:27 are
      considered functionally identical because they differ by a single amino acid
      substitution of Val > Ala at position 199, which is located in the alpha3 domain.
      To validate that HLA-B*44:02:01:01 and -B*44:27 represent functionally identical
      alleles that might reflect a permissive mismatch in hematopoetic stem cell
      transplantation (HSCT), we determined their peptide-binding features. B
      lymphoblastic cells were lentivirally transduced with B*44:02 and B*44:27
      constructs and soluble recombinant molecules were purified by affinity
      chromatography. Peptides were isolated and sequencing of single peptides was
      performed using liquid chromatography-electrospray ionization-tandem mass
      spectrometry (LTQ-Orbitrap) technology. We demonstrate that the peptide motif of
      B*44:02(199Val) and B*44:27(199Ala) is identical. Both variants feature E at P2
      and Y, F, or W at POmega in their ligands. Most of the identified peptides are 9
      to 11 amino acids in length and approximately 20% of these ligands are shared
      between the alleles. Our results lead to the conclusion that B*44:02:01:01 and
      B*44:27 might have the same immune function, validating a theory that is now
      being used in deciding which donors to select in HSCT when there is no identical
      donor available.

PMID- 21872627
TI  - Association of polymorphisms in TLR genes and in genes of the Toll-like receptor
      signaling pathway with cancer risk.
AB  - Toll-like receptors (TLRs) constitute a family of receptors directly recognizing
      a wide spectrum of exogenous and endogenous ligands playing the key role in
      realization of innate and adaptive immune response, and participating in the
      processes of cell proliferation, survival, apoptosis, angiogenesis, tissue
      remodeling and repair. Polymorphisms in TLR genes may shift balance between pro-
      and anti-inflammatory cytokines, modulating the risk of infection, chronic
      inflammation and cancer. The short list of TLR polymorphisms perspective for
      oncogenomic investigations can include rs10008492, rs4833103, rs5743815,
      rs11466657, rs7696175 (TLR1-TLR6-TLR10 gene cluster); rs3804100, rs4696480, -196 
      -174 del (Delta22), GT-microsatellite polymorphism (TLR2); 829A/C (TLR3);
      rs5743836, rs352140 (TLR9). The extended list can additionally include rs4833095
      rs5743551, rs5743618 (TLR1); rs5743704, rs62323857, rs1219178642 (TLR2);
      rs5743305, rs3775291, rs121434431, rs5743316 (TLR3); rs5744168 (TLR5); rs179008
      (TLR7); rs3764880, rs2407992 (TLR8); rs352139, rs187084, rs41308230, rs5743844
      (TLR9); rs4129009 (TLR10). General reasons for discrepancies between studies are
      insufficiency of sample size, age/gender/BMI/ethnic/racial differences,
      differences in prevalence of infectious agent in case and control groups,
      differences in immune response caused by specific ligand, differences in
      stratification, methods of diagnostics of cancer or chronic inflammatory
      conditions, genotyping methods, and chance. Future well-designed studies on large
      samples should shed light on the significance of TLR polymorphisms for cancer
      prevention.

PMID- 21872628
TI  - Development and efficacy of novobiocin and rifampicin-resistant Aeromonas
      hydrophila as novel vaccines in channel catfish and Nile tilapia.
AB  - Three attenuated Aeromonas hydrophila vaccines were developed from the virulent
      2009 West Alabama isolates through selection for resistance to both novobiocin
      and rifampicin. When channel catfish (Ictalurus punctatus) were IP injected with
      4*105 colony-forming unit (CFU) of the mutants, no fish died. However, when the
      same age and size matched channel catfish were IP injected with similar amount of
      their virulent parents, 80-100% fish died. Similarly, when Nile tilapia
      (Oreochromis niloticus) were IP injected with 2*108 CFU of the mutants, no fish
      died. However, when Nile tilapia were IP injected with similar amount of the
      mutants, all fish died. Vaccination of channel catfish with the mutants at dose
      of 4*105 CFU/fish offered 86-100% protection against their virulent parents at 14
      days post vaccination (dpv). Vaccination of Nile tilapia with the mutants at dose
      of 2*108 CFU/fish offered 100% protection against their virulent parents at 14,
      28, and 56 dpv. Agglutination assay results suggested that protection elicited by
      the mutants was partially due to antibody-mediated immunity. Taken together, our
      results suggest that the three attenuated vaccines might be used to protect
      channel catfish and Nile tilapia against the highly virulent 2009 West Alabama
      isolates of A. hydrophila.

PMID- 21872629
TI  - Influenza vaccine oculorespiratory syndrome incidence is reduced in HIV.
AB  - Clinical experience suggests Oculorespiratory Syndrome (ORS) following influenza
      vaccination is rare in HIV but this is not well evaluated. We assessed ORS
      incidence in a randomized influenza vaccine trial of HIV participants. The
      overall incidence was 0.8% suggesting that influenza vaccine ORS incidence is
      reduced in HIV.

PMID- 21872630
TI  - Estimated acceptance of HPV vaccination among Italian women aged 18-26 years.
AB  - In Italy vaccination against human papillomavirus (HPV) was introduced in the
      national immunization programme in 2007; the primary target for this vaccination
      is 11-year-old females, whereas vaccination for older age groups is still a
      matter of debate. This project was carried out in the period 2007-2009 to
      estimate the acceptance rate among 18-26-year-old, to whom free-of-charge
      vaccination was actively offered. Socio-demographic factors associated with
      acceptance were also investigated. A sample of 1159 women was randomly selected
      from resident population lists of 10 Local Health Units in 6 of Italy's 21
      Regions; 1032 women were deemed eligible for the study. Of the eligible women,
      580 received at least one vaccine dose for an acceptance rate of 56.2% and 542
      received all three vaccine doses (52.6%). The acceptance rate was significantly
      higher for: residents of northern and central Italy (OR(adj)=2.22, 95%CI 1.64
      3.01 and OR(adj)=1.77, 95%CI, 1.20-2.61 respectively), compared to southern
      Italy; women with a high educational level (OR(adj)=1.41; 95%CI: 1.02-1.93); and
      students (OR(adj)=1.64; 95%CI: 1.13-2.37). The low immunization rate highlights
      the difficulties of reaching young adult women, although the current coverage
      rates observed in the primary target population of HPV vaccination campaign (64%)
      emphasize that achieving high coverage rates is challenging also in younger age
      groups. Our results suggest that it would be premature to extend the active free
      of-charge offer of HPV vaccination to older women and that efforts should be
      focused on the priority target, considering that the objective of 95% coverage
      established for this age group is still far from being attained.

PMID- 21872631
TI  - Human leukocyte antigen associations with humoral and cellular immunity following
      a second dose of measles-containing vaccine: persistence, dampening, and
      extinction of associations found after a first dose.
AB  - Previously we found human leukocyte antigen (HLA) associations with humoral
      immunity following a single dose of measles-containing vaccine. In this study, we
      sought to determine if HLA associations exist with humoral and cellular immunity
      following a second dose of measles-containing vaccine and if the associations we
      found with humoral immunity after the first dose persist following a second dose.
      We recruited a population-based sample of 346 schoolchildren, all who previously
      received two doses of a measles-containing vaccine. Molecular HLA classes I and
      II typing as well as humoral and cellular immune assays (measles-specific IgG
      antibody levels and lymphoproliferative response) were performed in these
      subjects. We found significant associations with class I HLA-B (p=0.05) as well
      as class II HLA-DPB1 (p=0.01) and -DPA1 (p=0.03) genes for measles vaccine
      induced antibody levels after the second dose. Similarly, we found significant
      associations with class II HLA-DQB1 (p=0.05) and -DRB1 (p=0.01) genes for measles
      specific lymphoproliferation after the second dose. While we found HLA
      associations after the second dose that we previously found after the first dose
      of measles containing vaccine, fewer alleles had statistically significant
      associations, suggesting that the second dose had a dampening or extinguishing
      effect on the HLA associations. It appears that the second dose overcomes HLA
      restriction through an as yet unknown mechanism. Future studies of HLA
      associations should consider both the effect of dose and the role that subsequent
      doses might play on genetic associations found with the response to a first dose.

PMID- 21872632
TI  - A single point mutation in framework region 3 of heavy chain affects viral
      neutralization dynamics of single-chain Fv against bovine herpes virus type 1.
AB  - We constructed functional recombinant single chain Fv (scFv) against bovine
      herpes virus type 1 (BoHV-1), aetiological agent of respiratory and genital
      diseases in cattle for which available vaccines do not provide adequate
      protection. The scFv against BoHV-1 with 18 amino acid long flexible linker
      (scFv3-18L; monomeric form) recognized target antigen and, also, neutralized BoHV
      1 in vitro. A comparison with recombinant scFv with 7 amino acid linker against
      BoHV-1 (scFv1-7L), capable of forming diabodies, indicated that a relatively
      higher concentration (two-fold) of monomer scFv3-18L is needed for virus
      neutralization as compared to scFv1-7L. A single point replacement mutation
      (Asp98 to Gly98) in the framework-3 (FR3) variable-region of scFv with 18 amino
      acid linker (scFv4m-18L), however, affected the viral neutralization in a dose
      dependent manner where 2.7 fold higher mutant scFv concentration was required to
      achieve virus neutralization. Despite differences in dose-dependent viral
      neutralization of the mutant scFv-18L, it detected viral antigen in an
      immunofluorescent assay. The outlined experiments demonstrate that recombinant
      scFv against BoHV-1, whether expressed as scFv or diabody, provide an effective
      antibody based therapeutic and immunodiagnostic protein. Further, single point
      substitution mutation in the FR3 can affect viral neutralization dynamics without
      affecting qualitative viral antigen recognition.

PMID- 21872633
TI  - Sero-epidemiology of measles-specific IgG antibodies and predictive factors for
      low or missing titres in a German population-based cross-sectional study in
      children and adolescents (KiGGS).
AB  - BACKGROUND AND OBJECTIVE: In the European Region, measles elimination is now
      targeted to 2015. To measure progress towards elimination age-group specific
      susceptibility targets have been defined. Age-specific measles susceptibility in
      children and adolescents was evaluated in Germany. Taking into account a broad
      range of socio-demographic, health- and vaccination status related variables,
      populations for vaccination campaigns were identified. METHOD: We analysed data
      from children aged 1-17 years in the representative German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS). Measles immunoglobulin G
      antibodies were measured in 13,977 participants by enzyme immunoassay (ELISA).
      Bivariate and multivariate logistic regression analyses were used to determine
      parental and infant related factors associated with measles susceptibility.
      RESULTS: The overall prevalence of seronegativity in children tested for measles
      IgG aged 1-17 years was 10.0% (95% CI 9.4-10.7). The prevalence of seronegativity
      in the German population was below the WHO targets for measles elimination in
      children aged 2-9 year-olds but exceeded the target for 10-17 year-olds. Age
      differences in the level of seronegativity were found to be mainly due to
      differences in vaccination coverage. A higher level of susceptibility was
      observed if parents did not comply with the request to present the child's
      vaccination card. In vaccinated children, immigration, male gender, very young
      age at first vaccination and a longer time period since last vaccination were
      associated with a higher level of susceptibility. CONCLUSION: Further increase of
      the two-dose vaccination coverage is necessary in order to achieve the WHO
      targets. Catch up vaccination campaigns should focus on adolescents and
      immigrants.

PMID- 21872634
TI  - Protective immunity to ricin toxin conferred by antibodies against the toxin's
      binding subunit (RTB).
AB  - The B subunit (RTB) of ricin toxin is a galactose-/N-acetyl galactosamine
      specific lectin that promotes attachment and entry of ricin into host cells. RTB
      is also the archetype of the so-called R-type lectin family, whose members
      include haemagglutinins of botulinum neurotoxin (BoNT) progenitor toxins, as well
      as the binding subunits of cytolethal distending toxins. Although RTB is an
      appealing subunit vaccine candidate, as well as a potential target for
      immunotherapeutics, the degree to which RTB immunization elicits protective
      antibodies against ricin toxin remains unresolved. To address this issue, groups
      of mice were immunized with RTB and then challenged with 5*LD(50)s of ricin
      administered intraperitoneally. Despite high RTB-specific serum antibody titers,
      groups of RTB immunized mice were only partially immune to ricin challenge.
      Analysis of a collection of RTB-specific B cell hybridomas suggested that only a
      small fraction of antibodies against RTB have demonstrable neutralizing activity.
      Two RTB-specific neutralizing monoclonal IgG(1) antibodies, 24B11 and SylH3, when
      passively administered to mice, were sufficient to protect the animals against a
      5*LD(50) dose of ricin. Both 24B11 and SylH3 blocked ricin attachment to terminal
      galactose residues and prevented toxin binding to the surfaces of bone marrow
      derived macrophages (BMM), suggesting that they function by steric hindrance and
      recognize epitopes located on RTB's carbohydrate recognition sub-domains (1alpha
      or 2gamma). These data raise the possibility of using specific RTB sub-domains,
      rather than RTB itself, as antigens to more efficiently elicit neutralizing
      antibodies and protective immunity against ricin.

PMID- 21872635
TI  - CpG oligodeoxynucleotide and montanide ISA 206 adjuvant combination augments the
      immune responses of a recombinant FMDV vaccine in cattle.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      animals. To prevent the spread of FMDV, inactivated virus vaccines are used to
      immunize animals in developing countries. However, there are safety concerns. In
      addition, it is difficult to distinguish the vaccinated animals from those
      naturally infected ones. In our lab, we have developed a recombinant FMDV vaccine
      named A7. A7 contained multiple B cell and T cell epitopes, which reside in a
      capsid protein (VP1) of FMDV. To enhance its immunogenicity, A7 was formulated
      with CpG ODN RW03 in combination with Montanide ISA 206 (ISA), and the resultant
      vaccine (A7+ISA+CpG ODN RW03) was used to immunize mice and cattle. It was found
      that CpG ODN RW03 and ISA combination could facilitate A7 to induce a vigorous
      and long-lasting specific antibody response in mice and cattle. After FMDV
      challenge, 80% (4/5) of the calves immunized with A7+ISA+CpG ODN RW03 were
      protected, which was superior to those immunized with A7+ISA (25%, 1/4) or
      inactivated FMDV vaccine (50%, 2/4). These findings suggest that CpG ODN RW03
      could be used with Montanide ISA 206 as a potent adjuvant for recombinant FMDV in
      cattle.

PMID- 21872636
TI  - Protection against the toxic effects of Loxosceles intermedia spider venom
      elicited by mimotope peptides.
AB  - The venom of Loxosceles intermedia (Li) spiders is responsible for cutaneous
      lesions and other clinical manifestations. We previously reported that the
      monoclonal antibody LimAb7 can neutralize the dermonecrotic activity of crude Li
      venom. In this study, we observed that this antibody recognizes several proteins
      from the venom dermonecrotic fraction (DNF), including LiD1. Identifying the
      epitope of such a neutralizing antibody could help designing immunogens for
      producing therapeutic sera or vaccination approaches. To this aim, two sets of 25
      and 15-mer overlapping peptides that cover the complete amino acid sequence of
      LiD1 were synthesized using the SPOT technique. None of them was recognized by
      LimAb7, suggesting that the epitope is discontinuous. Then, the screening of four
      peptide phage-display libraries yielded four possible epitope mimics that,
      however, did not show any obvious similarity with the LiD1 sequence. These
      mimotopes, together with a 3D model of LiD1, were used to predict with the MIMOP
      bioinformatic tool the putative epitope region (residues C197, Y224, W225, T226,
      D228, K229, R230, T232 and Y248 of LiD1) recognized by LimAb7. This analysis and
      the results of alanine-scanning experiments highlighted a few residues (such as
      W225 and D228) that are found in the active site of different SMases D and that
      may be important for LiD1 enzymatic activity. Finally, the only mimotope
      NCNKNDHLFACW that interacts with LimAb7 by SPOT and its analog NSNKNDHLFASW were
      used as immunogens in rabbits. The resulting antibodies could neutralize some of
      the biological effects induced by crude Li venom, demonstrating a mimotope
      induced protection against L. intermedia venom.

PMID- 21872637
TI  - Safety assessment of lutein and zeaxanthin (Lutemax 2020): subchronic toxicity
      and mutagenicity studies.
AB  - Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the
      risk of cataracts and age-related macular degeneration. Lutemax 2020 is a lutein
      and zeaxanthin (including meso-isomer) enriched product obtained from Marigold
      flowers (Tagetes erecta L). The objective of the present study was to investigate
      adverse effects, if any, of Lutemax 2020 in acute and subchronic toxicity, and
      mutagenicity studies. In acute toxicity study in rats no lethality was noted at
      2000 mg Lutemax 2020/kg body weight (bw). In the subchronic study, Wistar rats
      (10/sex/group) were administered (gavage) lutein/zeaxanthin concentrate at dose
      levels of 0, 4, 40 and 400mg/kg bw/day for 90-days. Compared with the control
      group, administration of lutein/zeaxanthin concentrate did not result in any
      toxicologically significant treatment-related changes in clinical observations,
      ophthalmic examinations, body weights, body weight gains, feed consumption, and
      organ weights. No toxicologically relevant findings were noted in urinalysis,
      hematology or clinical biochemistry parameters at the end of the treatment or
      recovery period. Terminal necropsy did not reveal any treatment-related gross or
      histopathology findings. The results of mutagenicity testing in Salmonella
      typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level
      (NOAEL) for lutein/zeaxanthin concentrate was determined as 400mg/kg bw/day, the
      highest dose tested.

PMID- 21872638
TI  - Similar uptake profiles of microcystin-LR and -RR in an in vitro human intestinal
      model.
AB  - Microcystins (MCs) are cyclic hepatotoxins produced by various species of
      cyanobacteria. Their structure includes two variable amino acids (AA) leading to
      more than 80 MC variants. In this study, we focused on the most common variant,
      microcystin-LR (MC-LR), and microcystin-RR (MC-RR), a variant differing by only
      one AA. Despite their structural similarity, MC-LR elicits higher liver toxicity
      than MC-RR partly due to a discrepancy in their uptake by hepatic organic anion
      transporters (OATP 1B1 and 1B3). However, even though ingestion is the major
      pathway of human exposure to MCs, intestinal absorption of MCs has been poorly
      addressed. Consequently, we investigated the cellular uptake of the two MC
      variants in the human intestinal cell line Caco-2 by immunolocalization using an
      anti-MC antibody. Caco-2 cells were treated for 30min to 24h with several
      concentrations (1-50MUM) of both variants. We first confirmed the localization of
      OATP 3A1 and 4A1 at the cell membrane of Caco-2 cells. Our study also revealed a
      rapid uptake of both variants in less than 1h. The uptake profiles of the two
      variants did not differ in our immunostaining study neither with respect to
      concentration nor the time of exposure. Furthermore, we have demonstrated for the
      first time the nuclear localization of MC-RR and confirmed that of MC-LR.
      Finally, our results suggest a facilitated uptake and an active excretion of MC
      LR and MC-RR in Caco-2 cells. Further investigation on the role of OATP 3A1 and
      4A1 in MC uptake should be useful to clarify the mechanism of intestinal
      absorption of MCs and contribute in risk assessment of cyanotoxin exposure.

PMID- 21872639
TI  - Network-wide integration of stem cell-derived neurons and mouse cortical neurons
      using microfabricated co-culture devices.
AB  - Regeneration of damaged central nervous systems (CNS) is an important topic in
      neuroscience and neuroengineering. Grafting new neurons derived from pluripotent
      stem cells into damaged regions can be done to restore functions after injury.
      Little is known, however, about network-wide interactions between stem-cell
      derived neurons and CNS neurons. In this study, we developed a co-culture method
      of stem cell-derived neuronal networks and CNS networks and observed spontaneous
      activity in the co-culture samples. By using a microfabricated
      poly(dimethylsiloxane) device having two culture compartments and 20 connecting
      microconduits, we are able to compartmentalize P19-derived neurons and mouse
      cortical neurons and connect them via the microconduits. Furthermore, we combined
      the co-culture device and a microelectrode array (MEA)-based recording system and
      recorded spontaneous activity in the co-cultured networks. We found that periodic
      synchronized bursting spreading over both neuronal networks occurred during the
      second week in vitro and that P19-derived neurons in the co-cultured networks had
      different developmental processes compared with those grown in monoculture. These
      findings suggest that functional interactions form between P19-dervived neurons
      and mouse cortical neurons and that the co-culture method is useful for exploring
      the network-wide integrations between stem cell-derived neurons and CNS neurons.

PMID- 21872640
TI  - Molecular dynamics of ultradian glucocorticoid receptor action.
AB  - In recent years it has become evident that glucocorticoid receptor (GR) action in
      the nucleus is highly dynamic, characterized by a rapid exchange at the chromatin
      template. This stochastic mode of GR action couples perfectly with a
      deterministic pulsatile availability of endogenous ligand in vivo. The endogenous
      glucocorticoid hormone (cortisol in man and corticosterone in rodent) is secreted
      from the adrenal gland with an ultradian rhythm made up of pulses at
      approximately hourly intervals. These two components - the rapidly fluctuating
      ligand and the rapidly exchanging receptor - appear to have evolved to establish
      and maintain a system that is exquisitely responsive to the physiological demands
      of the organism. In this review, we discuss recent and innovative work that
      questions the idea of steady state, static hormone receptor responses, and
      replaces them with new concepts of stochastic mechanisms and oscillatory activity
      essential for optimal function in molecular and cellular systems.

PMID- 21872641
TI  - A physiological role for androgen actions in the absence of androgen receptor DNA
      binding activity.
AB  - We tested the hypothesis that androgens have physiological actions via non-DNA
      binding-dependent androgen receptor (AR) signaling pathways in males, using our
      genetically modified mice that express a mutant AR with deletion of the 2nd zinc
      finger of the DNA binding domain (AR(DeltaZF2)) that cannot bind DNA. In cultured
      genital skin fibroblasts, the mutant AR(DeltaZF2) has normal ligand binding
      ability, phosphorylates ERK-1/2 in response to 1 min DHT treatment (blocked by
      the AR antagonist bicalutamide), but has reduced androgen-dependent nuclear
      localization compared to wildtype (WT). AR(DeltaZF2) males have normal baseline
      ERK-1/2 phosphorylation, with a 1.5-fold increase in Akt phosphorylation in
      AR(DeltaZF2) muscle vs WT. To identify physiological actions of non-DNA binding
      dependent AR signaling, AR(DeltaZF2) males were treated for 6 weeks with
      dihydrotestosterone (DHT). Cortical bone growth was suppressed by DHT in
      AR(DeltaZF2) mice (6% decrease in periosteal and 7% decrease in medullary
      circumference vs untreated AR(DeltaZF2) males). In conclusion, these data suggest
      that non-DNA binding dependent AR actions suppress cortical bone growth, which
      may provide a mechanism to fine-tune the response to androgens in bone.

PMID- 21872642
TI  - Circadian rhythms and fertility.
AB  - Circadian rhythms impact on a wide range of physiological systems and this impact
      extends to fertility, such that disruptions to timing systems can impact upon
      reproductive capacity. This is highlighted most obviously in mutant mouse models
      whereby deletion or mutation of single genes results not only in disrupted
      circadian rhythmicity, but also compromised male and female reproductive
      function. In this review, we discuss the presence of circadian clocks in female
      and male reproductive tissues and the role these clocks play in the generation of
      oestrus cycles, ovulation, sperm generation, implantation and the maintenance of
      pregnancy. Given the increased incidence of shiftwork and international travel
      which disrupt circadian rhythmicity, and the increasing prevalence of
      reproductive technologies whereby early embryo development occurs without
      external time cues, it is important for us to consider the role of circadian
      rhythms in fertility.

PMID- 21872643
TI  - All-trans retinoic acid enhances bystander effect of suicide-gene therapy against
      medulloblastomas.
AB  - In our previous study we evaluated the antitumor effect of herpes simplex virus
      thymidine kinase gene (HSV-tk) on human medulloblastomas (MBs) in a therapeutic
      delivery system using the immortalized neural stem cell (NSC) line C17.2.
      However, our findings indicated that the bystander effect between C17.2tk and
      Daoy MB cells was weak compared to the bystander effect between NSCtk and C6
      glioma cells. Gap junction intercellular communication (GJIC) is the main
      mechanism mediating the bystander effect in HSV-tk gene therapy. All-trans
      retinoic acid (ATRA) has been shown to up-regulate the expression of Connexin43
      and GJIC. In this study we investigated the synergistic effect of ATRA and HSV-tk
      gene therapy in the treatment of MBs. We found that the expression of Connexin43
      in Daoy cells was significantly increased when cells were exposed to 3MUmol/l of
      ATRA (P<0.05). After co-culturing C17.2tk cells with Daoy cells at different
      ratios ranging from 1:1 to 1:16, ATRA significantly increased the bystander anti
      tumor effect compared to ATRA-untreated cells (P<0.05). In intracranial co
      implantation experiments, mice co-implanted with C17.2tk/Daoy cells and treated
      with a combination of ATRA and GCV had significantly smaller tumors compared to
      the animals treated with GCV alone (P<0.05). Together, our results show that ATRA
      enhanced the tumoricidal effect in HSVtk/GCV suicide gene therapy against Daoy MB
      cells by strengthening the bystander effect in vitro and in vivo.

PMID- 21872644
TI  - Neuroprotective effects of olprinone after cerebral ischemia/reperfusion injury
      in rats.
AB  - Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti
      inflammatory effects in addition to its inotropic and vasodilatory effects. The
      purpose of this study was to examine the beneficial effects of olprinone on
      cerebral ischemia reperfusion injury. In the present study, we examined the
      detailed mechanisms underlying the inhibitory effects of olprinone on
      inflammatory and apoptotic responses induced by middle cerebral artery occlusion
      (MCAo) in rats. Focal cerebral ischemia was induced by transient MCAo in the
      right hemisphere, via the external carotid artery into the internal carotid to
      block the origin of the median carotid artery. The rats were subjected to artery
      occlusion (2 h) followed by reperfusion (22 h). Olprinone was administered 5 min
      before reperfusion. MCAo-induced cerebral ischemia was associated with an
      increase in inducible nitric oxide synthase expression, nitrotyrosine formation,
      as well as IL-1beta expression and ICAM-1 expression in ischemic regions.
      Olprinone treatment showed marked reduction in infarct size compared with control
      rats. These expressions were markedly inhibited by olprinone treatment. We also
      demonstrated that olprinone reduces levels of apoptosis (TUNEL, Bax and Bcl-2
      expression) resulting in a reduction in the infarct volume in ischemia
      reperfusion brain injury. Based on these findings we propose that olprinone would
      be useful in lowering the risk of damage or improving function in ischemia
      reperfusion brain injury-related disorders.

PMID- 21872645
TI  - Uptake and release of metal ions by transferrin and interaction with receptor 1.
AB  - BACKGROUND: For a metal to follow the iron acquisition pathway, four conditions
      are required: 1-complex formation with transferrin; 2-interaction with receptor
      1; 3-metal release in the endosome; and 4-metal transport to cytosol. SCOPE OF
      THE REVIEW: This review deals with the mechanisms of aluminum(III), cobalt(III),
      uranium(VI), gallium(III) and bismuth(III) uptake by transferrin and interaction
      with receptor 1. MAJOR CONCLUSIONS: The interaction of the metal-loaded
      transferrin with receptor 1 takes place in one or two steps: a very fast first
      step (MUs to ms) between the C-lobe and the helical domain of the receptor, and a
      second slow step (2-6h) between the N-lobe and the protease-like domain. In
      transferrin loaded with metals other than iron, the dissociation constants for
      the interaction of the C-lobe with TFR are in a comparable range of magnitudes 10
      to 0.5MUM, whereas those of the interaction of the N-lobe are several orders of
      magnitudes lower or not detected. Endocytosis occurs in minutes, which implies a
      possible internalization of the metal-loaded transferrin with only the C-lobe
      interacting with the receptor. GENERAL SIGNIFICANCE: A competition with iron is
      possible and implies that metal internalization is more related to kinetics than
      thermodynamics. As for metal release in the endosome, it is faster than the
      recycling time of transferrin, which implies its possible liberation in the cell.
      This article is part of a Special Issue entitled Transferrins: Molecular
      mechanisms of iron transport and disorders.

PMID- 21872646
TI  - Synergistic inhibition of butyrylcholinesterase by galantamine and citalopram.
AB  - BACKGROUND: Many persons with Alzheimer's disease (AD) treated with galantamine
      appear to receive additional cognitive benefit from citalopram. Both drugs
      inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These
      enzymes co-regulate acetylcholine catabolism. In AD brain, AChE is diminished
      while BuChE is not, suggesting BuChE inhibition may be important in raising
      acetylcholine levels. BuChE is subject to activation at high acetylcholine levels
      reached at the synaptic cleft. The present study explores one way combining
      galantamine and citalopram could be beneficial in AD. METHODS: Spectrophotometric
      studies of BuChE catalysis in the absence or presence of galantamine or
      citalopram or both, were performed using the Ellman method. Data analysis
      involved expansion of our previous equation describing BuChE catalysis. RESULTS:
      Galantamine almost completely inhibited BuChE at low substrate concentrations
      (V(S)=43.6 MUM/min; V(S(gal))=0.34 MUM/min) without influencing the substrate
      activated form of the enzyme (V(SS)=64.0 MUM/min;V(SS(gal))=62.3 MUM/min).
      Conversely, citalopram inhibited both un-activated (V(S)=43.6 MUM/min;
      V(S(cit))=10.2 MUM/min) and substrate-activated (V(SS)=64.0 MUM/min;
      V(SS(cit))=47.3 MUM/min) forms of BuChE. Combined galantamine and citalopram
      increased inhibition of un-activated BuChE (V(S)=43.6 MUM/min;
      V(S(gal)(cit))=2.73 MUM/min) and substrate-activated form (V(SS)=64.0 MUM/min;
      V(SS(gal)(cit))=42.2 MUM/min). CONCLUSION: Citalopram and galantamine produce a
      combined inhibition of BuChE that is considered to be synergistic. GENERAL
      SIGNIFICANCE: Clinical benefit from combined galantamine and citalopram may be
      related to a synergistic inhibition of BuChE, facilitating cholinergic
      neurotransmission. This emphasizes the importance of further study into use of
      drug combinations in AD treatment.

PMID- 21872648
TI  - Identification of an entire set of tRNA molecules and characterization of
      cleavage sites of the intron-containing tRNA precursors in acidothermophilic
      crenarchaeon Sulfolobus tokodaii strain7.
AB  - The acidothermophilic crenarchaeon, Sulfolobus tokodaii strain7, was isolated
      from a hot spring in Beppu, Kyushu, Japan. Whole genomic data of this
      microorganism indicated that among 46 putative tRNA genes identified, 24 were
      interrupted tRNA genes containing an intron. A sequence comparison between the
      cDNA sequences for unspliced and spliced tRNAs indicated that all predicted tRNAs
      were expressed and all intron portions were spliced in this microorganism.
      However, the actual cleavage site in the splicing process was not determined for
      13 interrupted tRNAs because of the presence of the same nucleotides at both 5'
      and 3' border regions of each intron. The cleavage sites for all the introns,
      which were determined by an in vitro cleavage experiment with recombinant
      splicing endonuclease as well as cDNA sequencing of the spliced tRNAs, indicated
      that non-canonical BHB structure motifs were also recognized and processed by the
      splicing machinery in this organism. This is the first report to empirically
      determine the actual cleavage and splice sites of introns in the whole set of
      archaeal tRNA genes, and reassigns the exon-intron borders with a novel and more
      plausible non-canonical BHB structure.

PMID- 21872649
TI  - Mechanisms involved in lipid accumulation and apoptosis induced by 1-nitropyrene
      in Hepa1c1c7 cells.
AB  - 1-Nitropyrene (1-NP) is a nitro-polycyclic aromatic hydrocarbon (nitro-PAH)
      present in diesel exhaust and bound to particular matter in urban air. We show
      that 1-NP and the referent PAH benzo(a)pyrene (BP) induce apoptosis and a lipid
      accumulation dependent on cytochrome P450 1A1-metabolites in mouse hepatoma
      cells, whereas 1-amino-pyrene had no effect. The caspase inhibitor, N
      benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-fmk), inhibits 1
      NP-induced apoptosis, but failed to alter 1-NP-triggered lipid accumulation
      determined by Nile red staining. We further show that cholesterol and fatty acid
      contents are modified after nitro-PAH exposure and that 1-NP-induced cholesterol
      level is partially involved in related apoptosis. In parallel, the activity of
      the stearoyl-CoA desaturase 1 (SCD1), determined by fatty acid analysis, and its
      expression are reduced by 1-NP. The role of SCD1 in 1-NP-induced apoptosis is
      demonstrated in cells down-expressing SCD1, in which an increased apoptosis is
      observed, whereas the SCD1 overexpression elicits the opposite effects. In
      contrast, changes in SCD1 gene expression have no effect on the induced lipid
      accumulation. Moreover, 1-NP increases the activity of the AMP-dependent protein
      kinase (AMPK) leading to a caspase-independent apoptosis. Overall, our study
      demonstrates that the 1-NP-induced apoptosis is caspase- and AMPK-dependent, and
      is associated to a decrease of SCD1 expression which results in an alteration of
      lipid homeostasis.

PMID- 21872650
TI  - Thermal insight of mechanically activated bile acid powders.
AB  - Mechanical activation of pharmaceutical materials presents an important but
      poorly understood phenomenon of milled molecular crystals. In this work, a
      strategy was followed in an effort to understand this phenomenon, cryo-milled of
      both crystalline and amorphous counterpart of bile acids materials were
      characterized by X-ray powder diffraction (XRPD) and differential scanning
      calorimetry (DSC). The XRPD results for the 30-min milled crystalline powders
      displayed a characteristic amorphous halo patterns for all compounds tested. The
      DSC thermograms exhibited the typical glass transition temperatures (T(g))
      associated with amorphous but only for two materials. For the remaining four
      milled compounds, a rather interesting behavior was manifested through a
      characteristic exothermal bimodal peak. The findings seemed to suggest that the
      occurrence of this event was not related to the (T(g)), but likely to the melting
      temperature (T(m)). The DSC results for the melt-quenched (amorphous)
      ursodeoxycholic acid after cryo-milling revealed that the material crystallized
      after the influence of the mechanical stress, and a bimodal peak was also
      observed similar to that of the cryo-milled crystalline material. It is
      contemplated that the response of the physical instability of the disordered
      phase could be explained either by the result of surface crystallization kinetics
      which is different from that of the bulk crystallization, or by the creation of
      supersaturated dislocated crystal prior to amorphization.

PMID- 21872652
TI  - Dual functions of ginsenosides in protecting human endothelial cells against
      influenza H9N2-induced inflammation and apoptosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng is a precious traditional Chinese
      herbal medicine which has been utilized as herbal tonic for improving immunity.
      The active component, ginsenosides have been shown to possess various
      pharmacological functions including immunomodulation and cardiovascular
      protection. AIM OF THE STUDY: To investigate the immunomodulatory effect and anti
      apoptotic effect of ginsenosides on avian influenza-infected human endothelial
      cells, and to present evidence for the cardiovascular protection by ginseng
      during influenza infection. MATERIALS AND METHODS: Human umbilical vein
      endothelial cells (HUVECs) were infected with avian influenza H9N2/G1 to induce
      IP-10 production and cell death, cells were then incubated with ginsenosides PPT
      and Re. The level of IP-10 and microRNA was determined by ELISA and real-time PCR
      respectively. Cell death was determined by MTT, TUNEL and flow cytometry.
      RESULTS: Ginsenoside metabolite protopanaxatriol showed significant suppression
      effect on IP-10 production upon H9N2/G1 infection through up-regulation of miR
      15b expression. In addition, ginsenoside-induced cytoprotection was reflected in
      the increase of cell viability. Data from flow cytometry analysis and TUNEL assay
      also showed that ginsenoside Re could protect ECs from H9N2/G1-induced apoptosis
      and DNA damage. CONCLUSIONS: This report further supports the traditional belief
      for immunomodulatory effects of ginseng, also demonstrated the partial protective
      mechanism of ginsenosides on avian influenza infection and its related
      endothelial dysfunction.

PMID- 21872651
TI  - Early age conductive hearing loss causes audiogenic seizure and hyperacusis
      behavior.
AB  - Recent clinical reports found a high incidence of recurrent otitis media in
      children suffering hyperacusis, a marked intolerance to an otherwise ordinary
      environmental sound. However, it is unclear whether the conductive hearing loss
      caused by otitis media in early age will affect sound tolerance later in life.
      Thus, we have tested the effects of tympanic membrane (TM) damage at an early age
      on sound perception development in rats. Two weeks after the TM perforation, more
      than 80% of the rats showed audiogenic seizure (AGS) when exposed to loud sound
      (120 dB SPL white noise, < 1 min). The susceptibility of AGS lasted at least
      sixteen weeks after the TM damage, even the hearing loss recovered. The TM
      damaged rats also showed significantly enhanced acoustic startle responses
      compared to the rats without TM damage. These results suggest that early age
      conductive hearing loss may cause an impaired sound tolerance during development.
      In addition, the AGS can be suppressed by the treatment of vigabatrin, acute
      injections (250 mg/kg) or oral intakes (60 mg/kg/day for 7 days), an
      antiepileptic drug that inhibits the catabolism of GABA. c-Fos staining showed a
      strong staining in the inferior colliculus (IC) in the TM damaged rats, not in
      the control rats, after exposed to loud sound, indicating a hyper-excitability in
      the IC during AGS. These results indicate that early age conductive hearing loss
      can impair sound tolerance by reducing GABA inhibition in the IC, which may be
      related to hyperacusis seen in children with otitis media.

PMID- 21872647
TI  - Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and
      plasticity mechanisms.
AB  - Although the roles of dopaminergic signaling in learning and behavior are well
      established, it is not fully understood how the activity of dopaminergic neurons
      is dynamically regulated under different conditions in a constantly changing
      environment. Dopamine neurons must integrate sensory, motor, and cognitive
      information online to inform the organism to pursue outcomes with the highest
      reward probability. In this article, we provide an overview of recent advances on
      the intrinsic, extrinsic (i.e., synaptic), and plasticity mechanisms controlling
      dopamine neuron activity, mostly focusing on mechanistic studies conducted using
      ex vivo brain slice preparations. We also hope to highlight some unresolved
      questions regarding information processing that takes place at dopamine neurons,
      thereby stimulating further investigations at different levels of analysis.

PMID- 21872653
TI  - Anti-inflammatory effects of Pulvis Fellis Suis extract in mice with ulcerative
      colitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pulvis Fellis Suis is used in folk medicines to
      treat intestinal diseases, acute pharyngitis, whooping cough and asthma in China.
      Although several reports indicate that Pulvis Fellis Suis display diverse
      biological activities, such as antibacterial, anti-inflammatory and anti
      infusorian effects, its effects on ulcerative colitis have not been previously
      explored. AIM OF THE STUDY: The purpose of the present study is to assess the
      anti-inflammatory effect of Pulvis Fellis Suis (PFS) extract in acute ulcerative
      colitis model induced by trinitrobenzene sulfonic acid (TNBS) in mice. MATERIALS
      AND METHODS: Different doses of Pulvis Fellis Suis extract (100, 200 and
      400mg/kg/day) and sulfasalazine (500mg/kg/day) were administered by gavage for
      7days after the induction of colitis with TNBS. The efficacy of PFS was studied
      by macroscopical and histological scoring systems as well as myeloperoxidase
      (MPO) activity. Serum levels, including tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) were assayed by enzyme-linked immunoassay. The
      expression of cyclooxygenase (COX)-2 in the colons was assessed by
      immunohistochemical analysis. RESULTS: Treatment with PFS significantly
      attenuated macroscopic damage as compared with TNBS (P<0.01). Histological
      analysis showed that PFS improved the microscopic structure and preserved some
      areas of the colonic mucosa structure. In addition, administration of PFS
      effectively inhibited COX-2 protein expression and MPO activity accumulation. TNF
      alpha and IL-6 levels were also diminished dose-dependently (P<0.05, P<0.01), and
      IL-6 level obtained had no significant results by small dose of PFS. All the
      effects of these parameters were comparable to that of the standard
      sulfasalazine, especially at the highest dose level. CONCLUSIONS: We have shown
      for the first time that PFS has an anti-inflammatory effect in TNBS-induced
      ulcerative colitis which might be related to the reduction of up-regulated TNF
      alpha and IL-6 production, and that it may have therapeutic value in the setting
      of inflammatory bowel disease (IBD).

PMID- 21872654
TI  - Antibody-mediated resistance against plant pathogens.
AB  - Plant diseases have a significant impact on the yield and quality of crops. Many
      strategies have been developed to combat plant diseases, including the transfer
      of resistance genes to crops by conventional breeding. However, resistance genes
      can only be introgressed from sexually-compatible species, so breeders need
      alternative measures to introduce resistance traits from more distant sources. In
      this context, genetic engineering provides an opportunity to exploit diverse and
      novel forms of resistance, e.g. the use of recombinant antibodies targeting plant
      pathogens. Native antibodies, as a part of the vertebrate adaptive immune system,
      can bind to foreign antigens and eliminate them from the body. The ectopic
      expression of antibodies in plants can also interfere with pathogen activity to
      confer disease resistance. With sufficient knowledge of the pathogen life cycle,
      it is possible to counter any disease by designing expression constructs so that
      pathogen-specific antibodies accumulate at high levels in appropriate sub
      cellular compartments. Although first developed to tackle plant viruses and still
      used predominantly for this purpose, antibodies have been targeted against a
      diverse range of pathogens as well as proteins involved in plant-pathogen
      interactions. Here we comprehensively review the development and implementation
      of antibody-mediated disease resistance in plants.

PMID- 21872655
TI  - Evaluation of placental and lactational pharmacokinetics of PFOA and PFOS in the
      pregnant, lactating, fetal and neonatal rat using a physiologically based
      pharmacokinetic model.
AB  - Perfluoroalkyl carboxylates and sulfonates (PFAAs) have many consumer and
      industrial applications. Developmental toxicity studies in animals have raised
      concern about potential developmental effects of PFOA and PFOS in humans. We have
      developed PBPK models for PFAAs in the rat to help define a relationship between
      external dose, internal tissue concentrations, and observed adverse effects, and
      to understand how physiological changes that occur during gestation and lactation
      affect tissue distribution of PFAAs in the mother, fetus, and neonate. The models
      developed here expand upon a PBPK model for PFAAs in the adult female rat, and
      are consistent with available PK data. These models, along with the adult rat
      PFAA models, published in the companion paper, will help address concerns about
      possible health effects due to PFAA exposure in the fetus and neonate and will be
      useful in comparing PK across life stages.

PMID- 21872656
TI  - Assessing bioenergetic function in response to oxidative stress by metabolic
      profiling.
AB  - It is now clear that mitochondria are an important target for oxidative stress in
      a broad range of pathologies, including cardiovascular disease, diabetes,
      neurodegeneration, and cancer. Methods for assessing the impact of reactive
      species on isolated mitochondria are well established but constrained by the need
      for large amounts of material to prepare intact mitochondria for polarographic
      measurements. With the availability of high-resolution polarography and
      fluorescence techniques for the measurement of oxygen concentration in solution,
      measurements of mitochondrial function in intact cells can be made. Recently, the
      development of extracellular flux methods to monitor changes in oxygen
      concentration and pH in cultures of adherent cells in multiple-sample wells
      simultaneously has greatly enhanced the ability to measure bioenergetic function
      in response to oxidative stress. Here we describe these methods in detail using
      representative cell types from renal, cardiovascular, nervous, and tumorigenic
      model systems while illustrating the application of three protocols to analyze
      the bioenergetic response of cells to oxidative stress.

PMID- 21872657
TI  - Increased interaction of connexin43 with zonula occludens-1 during inhibition of
      gap junctions by G protein-coupled receptor agonists.
AB  - Astrocytes are extensively coupled through gap junctions (GJs) that are composed
      of channels mostly constituted by connexin43 (Cx43). This astroglial gap
      junctional intercellular communication (GJIC) allows propagation of ions and
      signaling molecules critical for neuronal activity and survival. It is
      drastically inhibited by a short-term exposure to endothelin-1 (ET-1) or to
      sphingosine-1-phosphate (S1P), both compounds being inflammatory mediators acting
      through activation of GTP-binding protein-coupled receptors (GPCRs). Previously,
      we have identified the GTPases G(i/o) and Rho as key actors in the process of S1P
      induced inhibition. Here, we asked whether similar mechanisms underlied the
      effects of ET-1 and S1P by investigating changes in the phosphorylation status of
      Cx43 and in the molecular associations of Cx43 with zonula occludens (ZO)
      proteins and occludin. We showed that the inhibitory effect of ET-1 on GJIC was
      entirely dependent on the activation of G(i/o) but not on Rho and Rho-associated
      kinase. Both ET-1 and S1P induced dephosphorylation of Cx43 located at GJs
      through a process mediated by G(i/o) and calcineurin. Thanks to co
      immunoprecipitation approaches, we found that a population of Cx43 (likely
      junctional Cx43) was associated to ZO-1-ZO-2-occludin multiprotein complexes and
      that acute treatments of astrocytes with ET-1 or S1P induced a G(i/o)-dependent
      increase in the amount of Cx43 linked to these complexes. As a whole, this study
      identifies a new mechanism of GJIC regulation in which two GPCR agonists
      dynamically alter interactions of Cx43 with its molecular partners.

PMID- 21872658
TI  - Negative regulation of adiponectin secretion by receptor interacting protein 140
      (RIP140).
AB  - RIP140 (receptor-interacting protein 140) is highly expressed in mature
      adipocytes and functions as a co-repressor for gene expression involved in lipid
      and glucose metabolism. In adipocytes, activated PKCepsilon (Protein kinase C
      epsilon) phosphorylates nuclear RIP140 which is then subsequently arginine
      methylated and exported to the cytoplasm. In the cytoplasm, RI140 can elicit
      additional activities. Here we report a new functional role for cytoplasmic
      RIP140 in adipocyte in regulating adiponectin secretion. Targeting cytoplasmic
      RIP140 by knocking down RIP140 itself or its nuclear export trigger, PKCepsilon,
      promotes the secretion of adiponectin without affecting the production or
      oligomerization of adiponectin. Consequentially, conditioned media from either
      RIP140- or PKCepsilon-silenced adipocytes, which contain higher levels of
      adiponectin, enhance glucose uptake in C2C12 cells and reduce gluconeogenesis in
      HepG2 cells. Further, these effects can be inhibited by an adiponectin
      neutralizing antibody. The effect of cytoplasmic RIP140 in regulating adiponectin
      secretion is via interacting with AS160, a known RIP140-interacting protein. This
      study reveals a new functional role for cytoplasmic RIP140 in modulating
      adiponectin vesicle secretion, and suggests that targeting cytoplasmic RIP140 may
      be a potentially effective therapeutic strategy to improve adiponectin secretion
      and possibly to manage metabolic disorders.

PMID- 21872659
TI  - Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14
      in DM1 muscle tissues.
AB  - Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an
      expansion of a CTG repeat located at the 3' untranslated region (UTR) of DMPK on
      chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has
      been reported to explain some of the symptoms of DM1 including insulin
      resistance, muscle wasting and myotonia. In this paper we analyzed the expression
      of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different
      expansion lengths and normal subjects (n=7). The MYH14 gene is located on
      chromosome 19q13.3 and encodes for one of the heavy chains of the so called class
      II "nonmuscle" myosins (NMHCII). MYH14 has two alternative spliced isoforms: the
      inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular
      head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results
      showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent
      expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large
      CTG expansions. Minigene assay indicated that levels of the MBNL1 protein
      positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of
      the MYH14 expression revealed a significant reduction in the DM1 muscle samples,
      both at mRNA and protein level. No differences were found between DM1 and
      controls in the skeletal muscle localization of MYH14, obtained through
      immunofluorescence analysis. In line with the thesis of an "RNA gain of function"
      hypothesis described for the CTG mutation, we conclude that the alterations of
      the MYH14 gene may contribute to the DM1 molecular pathogenesis.

PMID- 21872660
TI  - Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities
      in painful neuropathy of type 2 diabetes.
AB  - Painful diabetic neuropathy (PDN) is a common, yet devastating complication of
      type 2 diabetes. At this time, there is no objective test for diagnosing PDN. In
      the current study, we measured the peptidergic intraepidermal nerve fiber
      densities (IENFD) from hind paws of the db/db mouse, an animal model for type 2
      diabetes, during the period of mechanical allodynia from 6 to 12 weeks of age.
      Intraepidermal nerve fibers (IENF) of the hind footpads were identified by
      protein gene product (PGP) 9.5 immunohistochemistry. The peptidergic IENF were
      determined by double immunofluorescence using anti-PGP9.5 and antibodies against
      tropomyosin-receptor-kinase (Trk) A. We observed a significant increase in PGP9.5
      positive IENFD at 8 and 10 weeks of age. Similarly, Trk A-positive peptidergic
      IENF, which also express substance P and calcitonin gene related peptide in db/db
      mice, were observed to be elevated from 1.5 to 2 fold over controls. This
      upregulation ended at 16 weeks of age, in accordance with the reduction of
      mechanical allodynia. Anti-NGF treatment significantly inhibited the upregulation
      of peptidergic IENFD during the period of mechanical allodynia, suggesting that
      increased neurotrophism may mediate this phenomenon. In addition, SB203580, an
      inhibitor of p38, blocked the increase in peptidergic IENFD in db/db mice. The
      current results suggest that peptidergic IENFD could be a potential diagnostic
      indicator for PDN in type 2 diabetes. Furthermore, the inhibition of NGF-p38
      signaling could be a potential therapeutic strategy for treating this painful
      condition.

PMID- 21872661
TI  - Online immunoaffinity LC/MS/MS. A general method to increase sensitivity and
      specificity: How do you do it and what do you need?
AB  - There is an increased emphasis on hyphenated techniques such as immunoaffinity
      LC/MS/MS (IA-LC/MS/MS) or IA-LC/MRM. These techniques offer competitive
      advantages with respect to sensitivity and selectivity over traditional LC/MS and
      are complementary to ligand binding assays (LBA) or ELISA's. However, these
      techniques are not entirely straightforward and there are several tips and tricks
      to routine sample analysis. We describe here our methods and procedures for how
      to perform online IA-LC/MS/MS including a detailed protocol for the preparation
      of antibody (Ab) enrichment columns. We have included sample trapping and Ab
      methods. Furthermore, we highlight tips, tricks, minimal and optimal approaches.
      This technology has been shown to be viable for several applications, species and
      fluids from small molecules to proteins and biomarkers to PK assays.

PMID- 21872662
TI  - Structural characterization of BVU_3255, a methyltransferase from human intestine
      antibiotic resistant pathogen Bacteroides vulgatus.
AB  - Methylation is important for various cellular activities. To date, there is no
      report of any methyltransferase structure from the human intestine antibiotic
      resistant pathogen Bacteroides vulgatus. The protein BVU_3255 from B. vulgatus
      ATCC 8482 belongs to a SAM-dependent methyltransferase. Here, we report the
      crystal structure of apo BVU_3255, and its complexes with SAM and SAH, which
      revealed a typical class I Rossmann Fold Methyltransferase. Isothermal titration
      calorimetric studies showed that both SAM and SAH bind with equal affinity. The
      structural and sequence analysis suggested that BVU_3255 is a small molecule
      methyltransferase and involved in methylating the intermediates in ubiquinone
      biosynthesis pathway.

PMID- 21872663
TI  - The first homolog of a TRAF7 (TNF receptor-associated factor 7) gene in a
      mollusk, Crassostrea hongkongensis.
AB  - Tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) is one of
      several adaptor proteins that are critically involved in the activation of TLR
      dependent NF-kappaB signaling. In this report, the first mollusk TRAF7
      (designated ChTRAF7) homolog was isolated from Crassostrea hongkongensis by
      screening a suppression subtractive library. The full-length cDNA, 2290 bp in
      length, encodes a putative protein of 686 amino acids that contains a RING finger
      domain, an adjacent zinc finger domain, and seven WD40 repeats. ChTRAF7 is
      ubiquitously expressed in various tissues including digestive gland, mantle,
      gill, heart, hemocytes, muscle, and gonads, with the highest expression observed
      in gonads. Temporal expression of ChTRAF7 following bacterial infection shows
      that expression of ChTRAF7 in hemocytes decreases from 2 to 12 h post-challenge,
      and then recovered to the original level after 24 h. These results indicate that
      ChTRAF7 may play an important role in signal transduction in the immune response
      of oysters.

PMID- 21872664
TI  - Sleep deprivation reduces default mode network connectivity and anti-correlation
      during rest and task performance.
AB  - Sleep deprivation (SD) can alter extrinsic, task-related fMRI signal involved in
      attention, memory and executive function. However, its effects on intrinsic low
      frequency connectivity within the Default Mode Network (DMN) and its related anti
      correlated network (ACN) have not been well characterized. We investigated the
      effect of SD on functional connectivity within the DMN, and on DMN-ACN anti
      correlation, both during the resting state and during performance of a visual
      attention task (VAT). 26 healthy participants underwent fMRI twice: once after a
      normal night of sleep in rested wakefulness (RW) and once following approximately
      24h of total SD. A seed-based approach was used to examine pairwise correlations
      of low-frequency fMRI signal across different nodes in each state. SD was
      associated with significant selective reductions in DMN functional connectivity
      and DMN-ACN anti-correlation. This was congruent across resting state and VAT
      analyses, suggesting that SD induces a robust alteration in the intrinsic
      connectivity within and between these networks.

PMID- 21872665
TI  - Tactile, gustatory, and visual biofeedback stimuli modulate neural substrates of
      deglutition.
AB  - It has been well established that swallowing kinematics are modified with
      different forms of exogenous and endogenous input, however the underlying neural
      substrates associated with these effects are largely unknown. Our objective was
      to determine whether the swallowing BOLD response is modulated with heightened
      sensory modalities (taste, cutaneous electrical stimulation, and visual
      biofeedback) compared to water ingestion (control) in healthy adults across the
      age span. Habituation and sensitization were also examined for each sensory
      condition. Our principal findings are that each sensory swallowing condition
      activated components of the swallowing cortical network, plus regions associated
      with the particular sensory modality (i.e. primarily frontal motor planning and
      integration areas with visual condition). Overall, the insula was most commonly
      active among the sensory modalities. We also discuss gradual increases and
      decreases in BOLD signal with repeated exposures for each condition. We conclude
      that both stimulus- and intention-based inputs have unique cortical swallowing
      networks relative to their modality. This scientific contribution advances our
      understanding of the mechanisms of normal swallowing cortical control and has the
      potential to impact clinical uses of these modalities in treatments for
      neurogenic dysphagia.

PMID- 21872666
TI  - Abnormal cerebral cortical thinning pattern in adolescent girls with idiopathic
      scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) is a 3-D spinal deformity with uncertain
      etiology; abnormalities in brain development represent one of the possible
      explanatory concepts for its pathogenesis. The objective of this study is to
      investigate the brain maturation by thickness of cerebral cortex among female
      adolescents with and without idiopathic scoliosis. Fifty AIS patients with a
      typical right-thoracic curve pattern were compared with 40 age-matched healthy
      controls. Based on the T1-weighted magnetic resonance images, the thickness of
      cortical gray-matter was calculated using a well-validated surface measurement
      method. Focusing on adolescent participants within the age range with the
      frequent occurrences of AIS cases (i.e., 12 to 17 years), we observed that the
      cortical thickness declined significantly in almost all cortical lobes in normal
      subjects (Spearman correlation<-0.4; P <= 0.05) except temporal lobe in LH, while
      in AIS patients this decline was weakly correlated with age (Spearman
      correlation>-0.4) and largely insignificant (P >= 0.05). Quadratic regression
      results expressed the detailed difference in the age-related cortical changing
      pattern between the two groups. In addition, focal cortical thickness was
      significantly different in AIS patients compared with healthy controls in areas
      involved in motor and vestibular functions as well as object recognition. The
      findings from this study imply a different thinning pattern of the cerebral
      cortex during adolescence in patients with AIS; this may be primary (i.e.
      etiopathogenetic) or secondary (i.e. adaptation) to the development of scoliosis.

PMID- 21872667
TI  - First molecular evidence for the phylogenetic placement of the enigmatic snake
      genus Brachyorrhos (Serpentes: Caenophidia).
AB  - BrachyorrhosSchlegel, 1826a is a terrestrial-fossorial snake genus endemic to
      eastern Indonesia that has been assigned to six different families and
      subfamilies within Colubroidea (advanced snakes) over the past ~200 years. Here
      we report the first molecular sequences for Brachyorrhos and use them to test the
      position of the genus within snake phylogeny. Our Bayesian and Maximum Likelihood
      analyses of three mitochondrial and one nuclear gene strongly resolve
      Brachyorrhos within the rear-fanged semiaquatic Homalopsidae (Colubroidea), as
      the sister taxon to all other genera and sampled species.

PMID- 21872668
TI  - Multilocus phylogeny and species delimitation within the Natterer's bat species
      complex in the Western Palearctic.
AB  - Delimiting species is a crucial issue for many biological disciplines and is of
      primary importance for designing effective conservation plans. Traditional
      taxonomy based on morphological characters can be misled by the presence of
      phenotypic plesiomorphism or adaptative convergence. The use of multiple locus
      genetic data appears thus as a powerful tool for recognizing species boundaries.
      In this study, we used six nuclear introns and two mitochondrial markers to
      conduct a phylogenetic study of the Myotis nattereri species complex in the
      Western Palearctic. We combined tree-based and non-tree-based analyses, and also
      used concatenated phylogenetic methods of the separated nuclear and mitochondrial
      dataset as well as a recent coalescence-based multilocus approach. The strong
      concordance between the results of the analyses conducted confirms that M.
      nattereri is a paraphyletic group that is composed of four well-differentiated
      lineages in the study area. In the framework of the unified species concept,
      these four clades can be confidently considered as four valid species. This
      recognition of new cryptic species in the Western Mediterranean region shows that
      the biodiversity of this well-studied area is still not fully understood.

PMID- 21872669
TI  - The effect of molecular weight on hyaluronan's cartilage boundary lubricating
      ability--alone and in combination with proteoglycan 4.
AB  - OBJECTIVES: (1) assess the molecular weight dependence of hyaluronan's (HA)
      cartilage boundary lubricating ability, alone and in combination with
      proteoglycan 4 (PRG4), at physiological concentrations; (2) determine if HA and
      PRG4 interact in solution via electrophoretic mobility shift assay (EMSA).
      METHODS: The cartilage boundary lubricating ability of a broad range of MW HA (20
      kDa, 132 kDa, 780 kDa, 1.5 MDa, and 5 MDa) at 3.33 mg/ml, both alone and in
      combination with PRG4 at 450 MUg/ml, was assessed using a previously described
      cartilage-on-cartilage friction test. Static, MU(static, Neq), and kinetic,
      <MU(kinetic, Neq)>, were calculated. An EMSA was conducted with PRG4 and
      monodisperse 150 kDa and 1,000 kDa HA. RESULTS: Friction coefficients were
      reduced by HA, in a MW-dependent manner. Values of <MU(kinetic, Neq)> in 20 kDa
      HA, 0.098 (0.089, 0.108), were significantly greater compared to both 780 kDa,
      0.080 (0.072, 0.088), and 5 MDa, 0.079 (0.070, 0.089). Linear regression showed a
      significant correlation between both MU(static, Neq) and <MU(kinetic, Neq)>, and
      log HA MW. Friction coefficients were also reduced by PRG4, and with subsequent
      addition of HA; however the synergistic effect was not dependent on HA MW. Values
      of <MU(kinetic, Neq)> in PRG4, 0.080 (0.047, 0.113), were significantly greater
      than values of PRG4+various MW HA (similar in value, averaging 0.040 (0.033,
      0.047)). EMSA indicated that migration of 150 kDa and 1,000 kDa HA was retarded
      when combined with PRG4 at high PRG4:HA ratios. CONCLUSIONS: These results
      suggest alterations in HA MW could significantly affect synovial fluid's
      cartilage boundary lubricating ability, yet this diminishment in function could
      be circumvented by physiological levels of PRG4 forming a complex, potentially in
      solution, with HA.

PMID- 21872670
TI  - The associations between parity, other reproductive factors and cartilage in
      women aged 50-80 years.
AB  - OBJECTIVE: Sex hormones and reproductive factors may be important for
      osteoarthritis (OA). The aim of this study was to describe the associations of
      parity, use of hormone replacement therapy (HRT) and oral contraceptives (OCs)
      with cartilage volume, cartilage defects and radiographic OA in a population
      based sample of older women. DESIGN: Cross-sectional study of 489 women aged 50
      80 years. Parity, use of HRT and OC was assessed by questionnaire; knee cartilage
      volume and defects by magnetic resonance imaging and knee joint space narrowing
      (JSN) and osteophytes by X-ray. RESULTS: Parity was associated with a deficit in
      total knee cartilage volume [adjusted beta=-0.69 ml, 95% confidence interval (CI)
      -1.34, -0.04]. Increasing parity was associated with decreasing cartilage volume
      in both the tibial compartment and total knee (both P trend <0.05). Parity was
      also associated with greater cartilage defects in the patella compartment
      [adjusted odds ratio (OR)=2.87, 95% CI=1.39, 5.93] but not other sites. There was
      a consistent but non-significant increase in knee JSN (OR=2.78, 95% CI=0.75,
      10.31) and osteophytes (OR=1.69, 95% CI=0.59, 4.82) for parous women. Use of HRT
      and/or OC was not associated with cartilage volume, cartilage defects or
      radiographic change. CONCLUSIONS: Parity (but not use of HRT or OC) is
      independently associated with lower cartilage volume primarily in the tibial
      compartment and higher cartilage defects in the patella compartment in this
      population-based sample of older women.

PMID- 21872671
TI  - Post-training intra-basolateral amygdala infusions of norepinephrine block
      sevoflurane-induced impairment of memory consolidation and activity-regulated
      cytoskeletal protein expression inhibition in rat hippocampus.
AB  - Considerable evidence indicates that the noradrenergic system of the basolateral
      amygdala (BLA) participates in the consolidation of various types of emotionally
      arousing memories. We previously reported that administration of an anesthetic
      dose of sevoflurane immediately after continuous multiple-trail inhibition
      avoidance (CMIA) training impaired memory consolidation. This experiment
      investigated whether posttraining noradrenergic activation of the BLA is
      sufficient to reverse the memory impairing effect of sevoflurane. Adult male
      Sprague-Dawley rats received bilateral injections of norepinephrine (NE 0.3, 1.0,
      or 3.0 MUg/0.5 MUl) or normal saline (NS 0.5 MUl) immediately after training in a
      CMIA paradigm. Subsequently, the rats were exposed to sevoflurane (2% inspired)
      or air for 2h. Norepinephrine produced a dose-dependent enhancement of memory
      consolidation on a 24-h retention test. The highest dose of NE tested (3.0
      MUg/0.5 MUl) blocked sevoflurane-induced impairment of memory consolidation and
      reversed the inhibitory effect of sevoflurane on activity-regulated cytoskeletal
      protein (Arc) expression in the hippocampus 2h after training. These findings
      provide evidence that the mechanism mediating the memory-impairing effect of
      sevoflurane involves a network interaction between the BLA noradrenergic system
      and modulation of Arc protein expression in the hippocampus.

PMID- 21872673
TI  - The fat body of bullfrog (Lithobates catesbeianus) tadpoles during metamorphosis:
      changes in mass, histology, and melatonin content and effect of food deprivation.
AB  - The fat body of Lithobates catesbeianus (formerly Rana catesbeiana) tadpoles was
      studied during metamorphosis and after food deprivation in order to detect
      changes in its weight, adipocyte size, histology, and melatonin content. Bullfrog
      tadpoles have large fat bodies throughout their long larval life. Fat bodies
      increase in absolute weight, and weight relative to body mass, during late stages
      of prometamorphosis, peaking just before climax, and then decreasing, especially
      during the latter stages of transformation into the froglet. The climax decrease
      is accompanied by a reduction in size of adipocytes and a change in histology of
      the fat body such that interstitial tissue becomes more prominent. Food
      deprivation for a month during early prometamorphosis significantly decreased fat
      body weight and adipocyte size but did not affect the rate of development.
      However, food restriction just before climax retarded development, suggesting
      that the increased nutrient storage in the fat body before climax is necessary
      for metamorphic progress. Melatonin, which might be involved in the regulation of
      seasonal changes in fat stores, stayed approximately at the same level during
      most of larval life, but increased sharply in the fat body during the late stages
      of climax. The findings show that the rate of development of these tadpoles is
      not affected by starvation during larval life as long as they can utilize fat
      body stores for nourishment. They also suggest that the build up of fat body
      stores just before climax is necessary for progress during the climax period when
      feeding stops.

PMID- 21872672
TI  - Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the
      role of hippocampal brain-derived neurotrophic factor.
AB  - Chronic exposure to opiates impairs spatial learning and memory. Given the well
      known beneficial effects of voluntary exercise on cognitive functions, we
      investigated whether voluntary exercise would ameliorate the cognitive deficits
      that are induced by morphine dependence. If an effect of exercise was observed,
      we aimed to investigate the possible role of hippocampal brain-derived
      neurotrophic factor (BDNF) in the exercise-induced enhancement of learning and
      memory in morphine-dependent rats. The rats were injected with bi-daily doses
      (10mg/kg, at 12h intervals) of morphine over a period of 10 days of voluntary
      exercise. Following these injections, a water maze task was performed twice a day
      for five consecutive days, followed by a probe trial 2 days later. A specific
      BDNF inhibitor (TrkB-IgG chimera) was used to block the hippocampal BDNF action
      during the 10 days of voluntary exercise. We found that voluntary exercise
      blocked the ability of chronic morphine to impair spatial memory retention. A
      blockade of the BDNF action blunted the exercise-induced improvement of spatial
      memory in the dependent rats. Moreover, the voluntary exercise diminished the
      severity of the rats' dependency on morphine. This study demonstrates that
      voluntary exercise ameliorates, via a TrkB-mediated mechanism, the cognitive
      deficits that are induced by chronic morphine. Thus, voluntary exercise might be
      a potential method to ameliorate some of the deleterious behavioral consequences
      of the abuse of morphine and other opiates.

PMID- 21872674
TI  - [Clinical problems in medical mycology: problem number 44].

PMID- 21872676
TI  - HIV-1 proteins join the family of LIM kinase partners. New roads open up for HIV
      1 treatment.
AB  - LIM kinases (LIMK) exert their functions by recruiting many macromolecular
      partners that could contribute to modulate LIMK activity in a positive or
      negative manner. In addition to proteins that interact with LIMK in human or
      animal cells and tissues, recent data show that LIMK activity is also influenced
      by HIV-1 viral proteins. These results suggest new strategies for the treatment
      of HIV-1 infection, based on the inhibition of LIMK-mediated cofilin inactivation
      and consequent actin depolymerization. Further efforts are however required to
      unravel the mechanism by which the virus interferes with LIMK activity and with
      the right balance of actin remodeling.

PMID- 21872675
TI  - [Clinical problems in medical mycology: problem number 43].

PMID- 21872677
TI  - Message from Director General.

PMID- 21872678
TI  - Message from Dean of Faculty of Medicine, Khon Kaen University. Preface.

PMID- 21872679
TI  - Effect of light intensity on Opisthorchis viverrini cercarial shedding levels
      from Bithynia snails--a preliminary study.
AB  - Opisthorchis viverrini requires Bithynia snails as the first intermediate host
      and cyprinid fish as the second intermediate host. Very low natural infection
      rates have been reported in Bithynia snails, but very high rates have been found
      in cyprinid fish in the same endemic region. This study investigated the effect
      of light intensity, the most important stimulus, on the quantity of O. viverrini
      cercariae shed from naturally infected Bithynia (Digoniostoma) siamensis
      goniomphalos snails. Snails were evaluated for cercariae output every hour after
      exposure to various light intensities for a total period of 7h. The same infected
      snail was tested under different intensities of light: in the dark, and at 1000,
      3000 and 5000 lx. The data showed that under exposure to 1000 and 3000 lx of
      light, the average percentage and number of cercariae released were higher than
      that exposed to 5000 lx during the first 2h of the experiment. In contrast, under
      higher illumination (5000 lx) a longer time (6h) was required to stimulate the
      peak emergence of cercariae. Darkness was not able to induce O. viverrini
      cercariae emergence. Among the three intensities of light, exposure at 1000 lx
      induced the highest average number of released cercariae per snail and the
      highest percentage of cercarial emergence within the first 2h (125, 54.86%),
      followed by exposure at 3000 lx (69, 25.58%) and 5000 lx (12, 7.78%). The results
      suggest that the light intensity of 1000 lx for 2h would be optimal for O.
      viverrini cercarial shedding from naturally infected B. (D.) siamensis
      goniomphalos snails.

PMID- 21872680
TI  - Serum cancer biomarker discovery through analysis of gene expression data sets
      across multiple tumor and normal tissues.
AB  - The development of convenient serum bioassays for cancer screening, diagnosis,
      prognosis, and monitoring of treatment is one of top priorities in cancer
      research community. Although numerous biomarker candidates have been generated by
      applying high-throughput technologies such as transcriptomics, proteomics, and
      metabolomics, few of them have been successfully validated in the clinic. Better
      strategies to mine omics data for successful biomarker discovery are needed.
      Using a data set of 22,794 tumor and normal samples across 23 tissues, we
      systematically analyzed current problems and challenges of serum biomarker
      discovery from gene expression data. We first performed tissue specificity
      analysis to identify genes that are both tissue-specific and up-regulated in
      tumors compared to controls, but identified few novel candidates. Then, we
      designed a novel computation method, the multiple normal tissues corrected
      differential analysis (MNTDA), to identify genes that are expected to be
      significantly up-regulated even after their expressions in other normal tissues
      are considered, and, in a simulation study, showed that the multiple normal
      tissues corrected differential analysis outperformed the single tissue
      differential analysis combined with tissue specificity analysis. By applying the
      multiple normal tissues corrected differential analysis, we identified some genes
      as novel biomarker candidates. However, the number of potential candidates was
      disappointingly small, exemplifying the difficulty of finding serum cancer
      biomarkers. We discussed a few important points that should be considered during
      biomarker discovery from omics data.

PMID- 21872681
TI  - DW4TR: A Data Warehouse for Translational Research.
AB  - The linkage between the clinical and laboratory research domains is a key issue
      in translational research. Integration of clinicopathologic data alone is a major
      task given the number of data elements involved. For a translational research
      environment, it is critical to make these data usable at the point-of-need.
      Individual systems have been developed to meet the needs of particular projects
      though the need for a generalizable system has been recognized. Increased use of
      Electronic Medical Record data in translational research will demand generalizing
      the system for integrating clinical data to support the study of a broad range of
      human diseases. To ultimately satisfy these needs, we have developed a system to
      support multiple translational research projects. This system, the Data Warehouse
      for Translational Research (DW4TR), is based on a light-weight, patient-centric
      modularly-structured clinical data model and a specimen-centric molecular data
      model. The temporal relationships of the data are also part of the model. The
      data are accessed through an interface composed of an Aggregated Biomedical
      Information Browser (ABB) and an Individual Subject Information Viewer (ISIV)
      which target general users. The system was developed to support a breast cancer
      translational research program and has been extended to support a gynecological
      disease program. Further extensions of the DW4TR are underway. We believe that
      the DW4TR will play an important role in translational research across multiple
      disease types.

PMID- 21872682
TI  - Evaluation of the therapeutic efficacy of Mentha crispa in the treatment of
      giardiasis.
AB  - It's estimated that around 200 million people are annually infected with Giardia
      lamblia, making the disease a major cause of morbidity worldwide. The current
      treatment of giardiasis includes the use of several drugs, among them, herbal
      medicines formulated with Mentha crispa. Thus, the purpose of this study was to
      evaluate the therapeutic efficacy of M. crispa in the treatment of giardiasis.
      The research consisted initially of a cross-sectional study for the selection of
      subjects with giardiasis. After that, there was a randomized, open, in parallel
      with active control study, in order to verify the therapeutic efficacy of M.
      crispa in the treatment of giardiasis. Coprology samples were collected from 1622
      patients between May 2005 and May 2007 for a series of parasitological
      examinations. Ninety-six patients with G. lamblia were selected, which were then
      distributed randomly into two groups: Secnidazole, consisting of 50 patients
      treated with 2g of Secnidazole and M. crispa, containing 46 patients treated with
      2g of M. crispa. After 7 days, healing was evaluated by enzyme immunoassay in a
      fresh fecal sample. Additionally, the subjects were questioned about possible
      adverse effects and answered a questionnaire covering socioeconomic and
      hydrosanitary issues. The analysis of the clinical trial data showed that the
      cure rate for the Secnidazole group (84.0%) was significantly higher (P=0.0002)
      as that verified in the M. crispa group (47.83%). Therefore, the study concludes
      that, in the dose used in this trial, the effect of M. crispa in the treatment of
      giardisis is less effective than that of Secnidazole.

PMID- 21872683
TI  - Expression of myelin genes in the developing chick retina.
AB  - In submammalian animals including chicks, the retina contains oligodendrocytes
      (OLs), and axons in the optic fiber layer are wrapped with compact myelin within
      the retina; however, the expression of myelin genes in the chick retina has not
      been demonstrated yet. In the present study, we examined the expression of three
      myelin genes (proteolipid protein, PLP; myelin basic protein, MBP; cyclic
      nucleotide phosphodiesterase, CNP) and PLP in the developing chick retina, in
      comparison to the localization of Mueller cells. In situ hybridization
      demonstrated that all three myelin genes began to be expressed at E14 in the
      chick embryo retina. They are mostly restricted to the ganglion cell layer and
      the optic fiber layer, with a few exceptions in the inner nuclear layer where
      Mueller cells reside; however, PLP mRNA+ cells do not express glutamine
      synthetase, or vice versa. The present results elucidate that myelin genes are
      expressed only by OLs that are mostly localized in the innermost layer of the
      developing chick retina.

PMID- 21872684
TI  - Interferon regulatory factors: beyond the antiviral response and their link to
      the development of autoimmune pathology.
AB  - Abnormal production of interferon type I has been widely related to multiple
      autoimmune diseases, particularly systemic lupus erythematosus (SLE). It has been
      considered the molecular signature characterized by the overexpression of type I
      Interferon related genes in SLE patients. Among these, are the interferon
      regulatory factors (IRF). These transcription factors have been involved in the
      innate immune response, mainly the one related to the defense against viral
      infections; the development of immune cells and carcinogenesis. The role of IRF
      in autoimmune pathology has been addressed in diverse murine models. However,
      evidence in humans is quite scant. This review will focus on the evidence that
      supports the role of IRF in the development or susceptibility to autoimmune
      diseases. Specific emphasis will be made over the role of IRF-5 and IRF-7, since
      evidence of its association to the development of pathology, particularly
      systemic lupus erythematosus is the strongest.

PMID- 21872685
TI  - Systematic search for neutropenia should be part of the first screening in
      patients with poikiloderma.
AB  - Poikiloderma occurs in a number of hereditary syndromes, the best known of which
      is Rothmund-Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis
      Congenita (DC) with high genetic heterogeneity and Clericuzio-type Poikiloderma
      with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the
      RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10
      patients referred for syndromic poikiloderma and negative for RECQL4 sequencing
      analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous
      nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female
      child presenting with generalized poikiloderma, dental dysplasia, gingivitis,
      nail dystrophy, palmoplantar keratoderma and pachyonychia of the great toenails.
      Previously undetected and silent neutropenia was evidenced after C16orf57
      molecular analysis. Neutropenia was absent in the C16orf57-negative patients.
      This report confirms that neutrophil count should be performed in all patients
      with poikiloderma to target the C16orf57 gene sequencing analysis, prior to
      RECQL4 analysis.

PMID- 21872686
TI  - Remodeling markers are associated with larger intracortical surface area but
      smaller trabecular surface area: a twin study.
AB  - All postmenopausal women become estrogen deficient but not all remodel their
      skeleton rapidly or lose bone rapidly. As remodeling requires a surface to be
      initiated upon, we hypothesized that a volume of mineralized bone assembled with
      a larger internal surface area is more accessible to being remodeled, and so
      decayed, after menopause. We measured intracortical, endocortical and trabecular
      bone surface area and microarchitecture of the distal tibia and distal radius in
      185 healthy female twin pairs aged 40 to 61 years using high-resolution
      peripheral quantitative computed tomography (HR-pQCT). We used generalized
      estimation equations to analyze (i) the trait differences across menopause, (ii)
      the relationship between remodeling markers and bone surface areas, and (iii)
      robust regression to estimate associations between within-pair differences.
      Relative to premenopausal women, postmenopausal women had higher remodeling
      markers, larger intracortical and endocortical bone surface area, higher
      intracortical porosity, smaller trabecular bone surface area and fewer trabeculae
      at both sites (all p<0.01). Postmenopausal women had greater deficits in cortical
      than trabecular bone mass at the distal tibia (-0.98 vs. -0.12 SD, p<0.001), but
      similar deficits at the distal radius (-0.45 vs. -0.39 SD, p=0.79). A 1 SD higher
      tibia intracortical bone surface area was associated with 0.22-0.29 SD higher
      remodeling markers, about half the 0.53-0.67 SD increment in remodeling markers
      across menopause (all p<0.001). A 1 SD higher porosity was associated with 0.20
      0.30 SD higher remodeling markers. A 1 SD lower trabecular bone surface area was
      associated with 0.15-0.18 SD higher remodeling markers (all p<0.01). Within-pair
      differences in intracortical and endocortical bone surface areas at both sites
      and porosity at the distal tibia were associated with within-pair differences in
      some remodeling markers (p=0.05 to 0.09). We infer intracortical remodeling may
      be self perpetuating by creating intracortical porosity and so more bone surface
      for remodeling to occur upon, while remodeling upon the trabecular bone surface
      is self limiting because it removes trabeculae with their surface.

PMID- 21872688
TI  - Nutrition and child care: a healthy Head Start.

PMID- 21872689
TI  - Extending reach of science-based positions, messages.

PMID- 21872687
TI  - Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis
      through a beta-catenin-dependent mechanism.
AB  - Wnt10b is an established regulator of mesenchymal stem cell (MSC) fate that
      inhibits adipogenesis and stimulates osteoblastogenesis, thereby impacting bone
      mass in vivo. However, downstream mechanisms through which Wnt10b exerts these
      effects are poorly understood. Moreover, whether other endogenous Wnt ligands
      also modulate MSC fate remains to be fully addressed. In this study, we identify
      Wnt6 and Wnt10a as additional Wnt family members that, like Wnt10b, are
      downregulated during development of white adipocytes in vivo and in vitro,
      suggesting that Wnt6 and/or Wnt10a may also inhibit adipogenesis. To assess the
      relative activities of Wnt6, Wnt10a and Wnt10b to regulate mesenchymal cell fate,
      we used gain- and loss-of function approaches in bipotential ST2 cells and in 3T3
      L1 preadipocytes. Enforced expression of Wnt10a stabilizes beta-catenin,
      suppresses adipogenesis and stimulates osteoblastogenesis to a similar extent as
      Wnt10b, whereas stable expression of Wnt6 has a weaker effect on these processes
      than Wnt10a or Wnt10b. In contrast, knockdown of endogenous Wnt6 is associated
      with greater preadipocyte differentiation and impaired osteoblastogenesis than
      knockdown of Wnt10a or Wnt10b, suggesting that, among these Wnt ligands, Wnt6 is
      the most potent endogenous regulator of MSC fate. Finally, we show that knockdown
      of beta-catenin completely prevents the inhibition of adipogenesis and
      stimulation of osteoblast differentiation by Wnt6, Wnt10a or Wnt10b. Potential
      mechanisms whereby Wnts regulate fate of MSCs downstream of beta-catenin are also
      investigated. In conclusion, this study identifies Wnt10a and Wnt6 as additional
      regulators of MSC fate and demonstrates that mechanisms downstream of beta
      catenin are required for Wnt6, Wnt10a and Wnt10b to influence differentiation of
      mesenchymal precursors.

PMID- 21872690
TI  - Sustainability in foodservice operations: an update.

PMID- 21872691
TI  - Nutrition and the child-care setting.

PMID- 21872692
TI  - Parenting style and child feeding practices: potential mitigating factors in the
      etiology of childhood obesity.

PMID- 21872693
TI  - Validity of a measure to assess the child-care nutrition and physical activity
      environment.
AB  - BACKGROUND: Licensed child-care centers represent an opportunity to positively
      influence children's health behaviors. Valid and easy-to-use measures of the
      child-care environment are needed to assess the influence of environmental change
      on health. OBJECTIVE: To develop and validate a self-administered survey to
      assess the nutrition and physical activity environment of child-care centers, and
      to identify domains that may be evaluated adequately through self-report. DESIGN:
      A survey was developed to assess four areas related to nutrition and physical
      activity: center policies, practices related to the social environment, physical
      environment, and nutrition quality. Development involved review of the
      literature, existing measures, and regulations/standards as well as collaboration
      with a working group. The survey was pilot tested and feedback was sought from
      expert consultants. It was administered statewide and validated against a menu
      rating tool, interviews with a center director, and a direct observation tool
      that was developed for this study. PARTICIPANTS/SETTING: Participating sites were
      drawn from Child and Adult Care Food Program-participating licensed Connecticut
      child-care centers serving 13 or more children aged 3 to 5 years. Survey
      responses from 146 center directors were included, as were 62 center menus, and
      director interviews and observational data from 33 sites. PRIMARY
      OUTCOMES/STATISTICAL ANALYSES: Criterion validity of the survey was assessed
      through percent agreement with mirroring items in the additional measures.
      Healthy and unhealthy food scores were calculated for menu and survey tools, and
      Pearson correlations were computed. RESULTS: Percent agreement with criterion
      outcomes ranged from 39% to 97%, with 61% of items achieving agreement >=80%.
      Agreement was highest for nutrition and policy domains, and lowest for physical
      activity and barriers to promoting health. Correlations between food scores
      across measures were moderate. CONCLUSIONS: The self-report survey demonstrated
      adequate criterion validity. We make recommendations for improving validity of
      low-agreement items and for the use of more labor-intensive evaluation procedures
      for domains not adequately assessed through self-report.

PMID- 21872694
TI  - Body mass index and dietary intake among Head Start children and caregivers.
AB  - BACKGROUND: The US Head Start program serves low-income preschoolers and their
      caregivers and provides an opportunity for assessment and intervention on
      obesity. We sought to determine the prevalence of obesity among children and
      their caregivers and to identify variables that are associated with child body
      mass index (BMI) z scores and caregiver BMI. DESIGN/SETTING: Cross-sectional data
      on diet and BMI from 770 caregiver-child dyads recruited from 57 Head Start
      centers in Alabama and Texas. METHODS: Height and weight of each caregiver and
      child were measured using standardized protocols. Dietary intakes of caregiver
      child dyads were collected using three 24-hour dietary recalls and Block food
      frequency questionnaires. Data were collected between September 2004 and November
      2005. The larger Food Pyramid categories were divided into 17 food consumption
      groups and tested for their association with child BMI z scores. Analysis of
      variance was used to test if food groups were significantly associated with child
      BMI z score. RESULTS: The prevalence of obesity among children was 18.4%, 24.3%,
      and 37.3% among black, Hispanic, and white children, respectively (P<0.0001),
      whereas it was 58.3%, 41.4%, and 41.6% among black, Hispanic, and white
      caregivers, respectively (P<0.0001). Child BMI z scores and caregiver BMIs were
      correlated (r=0.16, P<0.0001). In multivariable models, children were 1.90 (95%
      confidence interval 1.31-2.74) times more likely to have BMI >=95th percentile if
      their caregiver was obese. Five variables (fruits, unsweetened beverages, low-fat
      dairy, race, and caregiver's BMI) were significantly associated with child BMI z
      scores. Fruits were inversely related, whereas unsweetened beverages, low-fat
      dairy, and caregiver's BMI were positively associated with child BMI z score
      (P<0.03). Compared to whites, black and Hispanic children had lower BMI z scores
      (P<0.05). CONCLUSIONS: The high prevalence of obesity in this population together
      with the observed inverse association between fruit consumption and BMI, if
      replicated in other studies, suggests that interventions that promote fruit
      consumption could have beneficial effects on child BMI.

PMID- 21872695
TI  - Dietary modeling shows that substitution of whole-grain for refined-grain
      ingredients of foods commonly consumed by US children and teens can increase
      intake of whole grains.
AB  - BACKGROUND: Currently available whole-grain foods are not frequently consumed,
      and few children achieve the whole-grain intake recommendation. OBJECTIVE: To
      investigate the influence on whole-grain consumption of substituting whole-grain
      for refined-grain ingredients of foods commonly consumed by children. DESIGN:
      Secondary cross-sectional analysis of publicly available food consumption data
      collected by the US Department of Agriculture. PARTICIPANTS/SETTING: A nationally
      representative sample of US children aged 9 to 18 years (n=2,349) providing 24
      hour dietary recall data in the 2003-2004 National Health and Nutrition
      Examination Survey. MAIN OUTCOME MEASURES: Whole-grain intake was modeled by
      replacing varying proportions of refined flour contained in foods such as pizza
      crust, pasta, breads, and other baked goods with whole-wheat flour, and by
      replacing a proportion of white rice with brown rice. Replacement levels were
      based on the acceptability of whole-grain foods tested among children in
      elementary schools, and ranged from 15% to 50%; the majority were <=25%.
      STATISTICAL ANALYSES PERFORMED: Sample-weighted mean premodeled and postmodeled
      whole-grain intake, standard errors, and statistical significance of differences
      between demographic subgroups were determined using SUDAAN (version 9.0.3, 2007,
      Research Triangle Institute, Research Triangle Park, NC). RESULT: Whole-grain
      intake increased 1.7 oz eq per day (from 0.5 to 2.2 oz eq/day). Premodeled and
      postmodeled whole-grain intakes were 6% and 28%, respectively, of total grain
      intake (7.7 oz eq/day). Major sources of postmodeled whole-grain intakes were
      breads/rolls (28.0%); pizza (14.2%); breakfast cereals (11.0%); rice/pasta
      (10.6%); quick breads such as tortillas, muffins, and waffles (10.8%); other
      baked goods (9.9%); and grain-based savory snacks other than popcorn (7.3%).
      Premodeled whole-grain intake differed by poverty level, but postmodeled whole
      grain intake did not. CONCLUSIONS: The substitution of whole grain for a specific
      proportion of refined grain ingredients of commonly consumed foods increased
      whole-grain intake and reduced disparities between demographic subgroups of
      children and teens.

PMID- 21872696
TI  - Trends in vitamin D intake from food sources among adults in the Minneapolis-St
      Paul, MN, metropolitan area, 1980-1982 through 2007-2009.
AB  - BACKGROUND: Changes in eating habits could potentially be contributing to vitamin
      D insufficiency among US adults. OBJECTIVE: Describe secular trends in vitamin D
      intake from food sources during the past 25 years. DESIGN: Trends in dietary
      vitamin D intake from 1980-1982 to 2007-2009 were examined using data collected
      from the Minnesota Heart Survey, a surveillance study of trends in risk factors
      for cardiovascular disease among probability samples of adults aged 25 to 74
      years in the Minneapolis-St Paul, MN, metropolitan area. Surveys were conducted
      in 1980-1982, 1985-1987, 1990-1992, 1995-1997, 2000-2002, and 2007-2009. One 24
      hour recall was collected from survey participants during each survey period.
      RESULTS: Vitamin D intake from food sources decreased between 1980-1982 and 2007
      2009 among men, with age-adjusted mean vitamin D intake decreasing from 7.24
      MUg/day in 1980-1982 to 6.15 MUg/day in 2007-2009 (P for trend <0.001). A
      decrease was also observed among women (4.77 MUg/day in 1980-1982 in comparison
      to 4.53 MUg/day in 2007-2009; P for trend <0.001). CONCLUSIONS: Results suggest
      that vitamin D intake from food sources has been on the decline during the past
      25 years among men and women, potentially contributing to vitamin D
      insufficiency.

PMID- 21872698
TI  - What role can child-care settings play in obesity prevention? A review of the
      evidence and call for research efforts.
AB  - Given the widespread use of out-of-home child care and an all-time high
      prevalence of obesity among US preschool-aged children, it is imperative to
      consider the opportunities that child-care facilities may provide to reduce
      childhood obesity. This review examines the scientific literature on state
      regulations, practices and policies, and interventions for promoting healthy
      eating and physical activity, and for preventing obesity in preschool-aged
      children attending child care. Research published between January 2000 and July
      2010 was identified by searching PubMed and MEDLINE databases, and by examining
      the bibliographies of relevant studies. Although the review focused on US child
      care settings, interventions implemented in international settings were also
      included. In total, 42 studies were identified for inclusion in this review: four
      reviews of state regulations, 18 studies of child-care practices and policies
      that may influence eating or physical activity behaviors, two studies of parental
      perceptions and practices relevant to obesity prevention, and 18 evaluated
      interventions. Findings from this review reveal that most states lack strong
      regulations for child-care settings related to healthy eating and physical
      activity. Recent assessments of child-care settings suggest opportunities for
      improving the nutritional quality of food provided to children, the time children
      are engaged in physical activity, and caregivers' promotion of children's health
      behaviors and use of health education resources. A limited number of
      interventions have been designed to address these concerns, and only two
      interventions have successfully demonstrated an effect on child weight status.
      Recommendations are provided for future research addressing opportunities to
      prevent obesity in child-care settings.

PMID- 21872697
TI  - Meal patterns and food choices of young African-American men: understanding
      eating within the context of daily life.
AB  - Although young African-American men are at particularly high risk of developing
      hypertension at an early age, dietary interventions that have successfully
      reduced blood pressure among African-American adults have not been translated
      into programs for this group. Life contexts such as school enrollment,
      participation in competitive athletics, and employment influence the daily
      activities and meal patterns of African-American men. This study explored the
      activities of young African-American men to identify opportunities to increase
      healthful food choices. A purposive sample was recruited that included five
      groups of African-American men aged 15 to 22 years (N=106): high school athletes
      and nonathletes, college athletes and nonathletes, and nonstudents. A structured
      interview guided participants through a description of their activities, meal
      patterns, and food choices during the course of a typical weekday. Common
      elements emerged that provided a contextual view of the participant meal patterns
      and food choices. These elements were sports team participation, college
      employment, school as a food source, nonstudent status, and eating dinner at
      home. These findings suggest opportunities for the design of dietary
      interventions for young African-American men that take into consideration how
      school, athletics, and employment may influence opportunities to eat regular
      meals that include healthful foods.

PMID- 21872699
TI  - Associations of infant feeding practices and picky eating behaviors of preschool
      children.
AB  - Picky eating behaviors are prevalent during childhood and are often linked to
      nutritional problems. However, information on the determinants of picky eating
      behaviors during infancy, when food acceptance patterns develop, is scarce. This
      study was conducted to evaluate the impact of infant feeding practices on the
      development of picky eating behaviors during preschool years. Baseline survey
      data from the Synergistic Theory and Research on Obesity and Nutrition Group Kids
      (STRONG Kids) program were used for this retrospective data analysis. Primary
      caregiver-child dyads were recruited from child-care centers in Eastern Illinois
      between February and July of 2009. A total of 129 self-reported responses from
      mothers of preschool-aged children were analyzed. Logistic regression was used to
      evaluate the association between infant feeding practices and picky eating
      behaviors. Children who were introduced to complementary foods before 6 months of
      age had 2.5 times higher odds of developing food neophobia and limited variety of
      foods (95% confidence interval [CI]: 1.01 to 5.93 and 1.06 to 5.73,
      respectively). Children who were breastfed exclusively for 6 months had lower
      odds of developing a preference for specific food-preparation methods by 78% (95%
      CI: 19% to 94%), food rejection by 81% (95% CI: 31% to 94%), and food neophobia
      by 75% (95% CI: 11% to 93%). Breastfeeding and introduction of complementary
      foods after 6 months of age reduced the odds of picky eating during early
      childhood. This study documents an association between infant-feeding practices
      and the development of picky eating behaviors in early childhood.

PMID- 21872701
TI  - Food access and cost in American Indian communities in Washington State.
AB  - Limited access to foods that make up a nutritious diet at minimal cost may
      influence eating behaviors and, ultimately, obesity. This study examined the
      number and type of food stores (convenience, grocery, supermarket) on federal
      reservations in Washington State, and the availability and cost of foods in the
      US Department of Agriculture Community Food Security Assessment Toolkit market
      basket, to describe the food environment of American Indians. Stores were
      identified by telephone survey of tribal headquarters, a commercial database, and
      on-site visitation. Foods were assessed using a standardized instrument
      containing 68 items in seven major food groups during April and May 2009. Store
      type and availability and cost of foods were recorded on a checklist. Fifty
      stores were identified on 22 American Indian reservations, including 25
      convenience, 16 grocery, and 9 supermarkets. Across all stores, about 38% of
      checklist items were available, with supermarkets having the most and convenience
      stores the fewest. Foods from the dairy and sugars/sweets groups were the most
      prevalent, while fresh fruits/vegetables were the least. Cost of the most
      commonly available items was lowest in supermarkets. Seventeen reservations did
      not have a supermarket on their reservation, and the nearest off-reservation
      supermarket was about 10 miles from the tribe's headquarters, which was used as
      the standard for distance calculations. These results demonstrate that American
      Indians living on federal reservations in Washington State may have limited
      access to foods that make up a nutritious diet at minimal cost.

PMID- 21872700
TI  - Acculturation, education, nutrition education, and household composition are
      related to dietary practices among Cambodian refugee women in Lowell, MA.
AB  - Refugees in the United States have higher rates of some chronic diseases than US
      born residents or other first-generation immigrants. This may be partially a
      result of dietary practices in the United States. There is limited information
      about which factors are related to dietary practices in refugee populations,
      particularly those who have been in the United States for 10 to 20 years.
      Research with Cambodian communities may be useful for examining the relationship
      between refugee characteristics and dietary practices. Two focus groups (n=11)
      and a survey (n=150) of Cambodian refugee women were conducted in Lowell, MA,
      from 2007 to 2008. chi(2) analyses, t tests, and analysis of variance tests were
      used to describe differences in dietary practices (24-hour recall and a targeted
      qualitative food assessment) by group characteristics. Higher acculturation was
      related to higher likelihood of eating brown rice/whole grains, and to lower
      likelihood of eating high-sodium Asian sauces. Higher education was related to
      higher likelihood of eating vegetables and fruits and to eating white rice fewer
      times. Nutrition education and receiving dietary advice from a health care
      provider were related to higher likelihood of eating whole grains/brown rice.
      Having a child at home was related to a higher likelihood of eating fast food.
      Among Cambodian refugees who have been in the United States for 10 to 20 years,
      dietary practices appear to have a relationship with acculturation (positive
      association), the interrupted education common to refugees (negative
      association), nutrition education from either programs or health care providers
      (positive association), and having a child at home (negative association).

PMID- 21872702
TI  - Acceptance of two US Department of Agriculture commodity whole-grain products: a
      school-based study in Texas and Minnesota.
AB  - Whole-grain intake among children and adolescents is below national
      recommendations, prompting efforts to increase intake in schools. The purpose of
      this study was to compare the acceptance of whole-grain pancakes and tortillas to
      refined grain counterparts when served as part of the school meal. Data were
      collected at 10 schools in Minnesota and seven schools in Texas during the Spring
      and Fall semesters of 2009. Three pancake and two tortilla products of varying
      red or white whole-wheat flour content were each served an average of four times
      per school. Aggregate plate waste was collected and percent consumption used to
      assess acceptance. Students rated each product on overall liking, taste, color,
      and softness on 5-point (elementary schools) or 9-point hedonic scales (middle
      and high schools). Analysis of covariance was used to compare intake and rating
      scores of all products. For all children, intake of whole-grain products was
      substantial (percent consumption ranging from 67% to 75%). No differences were
      noted in consumption of whole-wheat pancakes compared to refined wheat pancakes,
      while consumption of whole-wheat tortillas was lower than refined products. In
      elementary schools, overall liking scores of pancakes made with red whole-wheat
      and both types of whole-wheat tortillas were lower than refined products.
      However, in middle and high schools, overall liking scores of 100% red whole
      wheat pancakes and 66% white whole-wheat tortillas were similar to refined
      products. Substituting refined grain with whole-grain options represents a viable
      approach to increasing consumption of whole-grain products in schools.

PMID- 21872704
TI  - Nutrition practices and children's dietary intakes at 40 child-care centers in
      New York City.
AB  - Early childhood is a critical time to establish nutrition habits to prevent
      obesity. At least half of US children spend time in care outside of the home,
      where little is known about their dietary intakes and nutrition environment. The
      purpose of this study was to evaluate nutrition practices of group child-care
      centers in New York City and to assess whether dietary intakes of children at
      these centers meet nutrition recommendations. In 2005 and 2006, student research
      assistants administered surveys to directors of 40 child-care centers in three
      underserved communities (Central Brooklyn, East/Central Harlem, South Bronx) and
      in Manhattan, gathered menus, and observed beverages and foods consumed by 240 3-
      and 4-year-old children. Almost all centers provided beverages and foods
      recommended by national guidelines, including reduced-fat milk, 100% fruit juice,
      and whole grains. Some centers also provided higher-fat milk and sugar-sweetened
      beverages, but no centers provided soda. Drinking water was available in
      classrooms at only half of the centers. From observations at meal and snack times
      between 8 AM to 2 PM, <50% of children ate at least half of the daily recommended
      intake for each of five main food groups, with only 17% of children eating at
      least half of the daily recommended intake for vegetables and only 5% of children
      eating at least half of the daily recommended intake for vitamin E. Although many
      centers provided healthful beverages and foods to children, further efforts are
      needed to make water available as a beverage throughout the day and to improve
      dietary intakes, especially of vegetables and vitamin E-containing foods.

PMID- 21872705
TI  - What impact does plate size have on portion control?

PMID- 21872703
TI  - Tween sex differences in snacking preferences during television viewing.
AB  - Television viewing is associated with an increased risk in childhood obesity.
      Research surrounding food habits of tweens largely bypasses snacking preferences
      while watching television in the home. The aim of this cross-sectional study was
      to describe snacking prevalence by tween sex and to describe parental rules
      surrounding snacking while watching television at home. Survey data were obtained
      in 2008 from 4th- through 6th-grade students (n=1,557) who attended 12 New
      England schools. Complete self-reported measures (n=1,448) included demographics,
      household and bedroom television ownership, television watching frequency,
      snacking prevalence, snacking preferences, and parental rules regarding snacking
      while watching television. Comparisons were generated using chi(2) analyses.
      Overall, the majority of children (69.2%) snacked "sometimes" or "always" during
      television viewing, with the majority of responses (62.9%) categorized as foods.
      The most popular food snacks for both sexes in this sample were salty snacks
      (47.9%), with fruits and vegetables ranking a distant second (18.4%). Girls
      (22.6%) selected fruits and vegetables more frequently than boys (14.7%)
      (P=0.003). Of those drinking beverages (n=514), boys selected sugar-sweetened
      beverages more often than girls (43.5% vs 31.7%; P=0.006), and girls chose juice
      more often than boys (12.3% vs 6.1%; P=0.02). Overall, approximately half (53.2%)
      of the students consumed less-healthy snacks while watching television.
      Interventions for parents and both sexes of tweens focusing on healthy snacking
      choices may have long-term beneficial outcomes.

PMID- 21872706
TI  - Probe-based confocal endomicroscopy in Barrett's esophagus: the real deal or
      another tease?

PMID- 21872707
TI  - Endoscopic resection for early gastric cancer: one piece is better than dash to
      pieces.

PMID- 21872708
TI  - A double-masked, randomized, placebo-controlled trial of temporary endoscopic
      mucosal gastric electrical stimulation for gastroparesis.
AB  - BACKGROUND: Endoscopically placed, temporary gastric electrical stimulation
      (tGES) may relieve symptoms of gastroparesis (Gp) and predict permanent gastric
      electrical stimulation (GES) outcomes. OBJECTIVE: To measure effects of 72 hours
      of temporary GES on Gp symptoms. DESIGN, SETTING, AND PATIENTS: From 2005 to
      2006, we conducted a hospital-based, randomized, placebo-controlled, crossover
      trial of two consecutive, 4-day sessions (session 1 and session 2), enrolling 58
      patients (11 males, 47 females; mean age 46 years) with GP symptom histories of
      three etiologies (idiopathic, 38; diabetes mellitus, 13; postsurgical, 7).
      INTERVENTION: 72 continuous hours temporary GES was provided for group A during
      session 1, and for group B during session 2. MAIN OUTCOME MEASUREMENTS: Symptoms
      measured daily; gastric emptying, electrogastrography, and quality of life
      measured at baseline and session close. RESULTS: In session 1, vomiting decreased
      in both groups, but was greater with stimulation, resulting in a day 3 difference
      of -1.02 (95% CI, -1.62 to -0.42; P < .001). Scores did not return to baseline
      during washout; on day 4, the difference persisted at -1.08 (95% CI, -1.81 to 
      0.35; P = .005). In session 2, vomiting slightly decreased with stimulation and
      slightly increased without it; at day 8, the nonactivated group had
      nonsignificantly greater vomiting, 0.12 (-0.68 to 0.92; P = .762). An overall
      treatment effect of a slight, nonsignificant daily decrease in average vomiting
      scores, -0.12 (-0.26 to 0.03; P = .116), was observed by pooling stimulation
      effects across sessions. LIMITATIONS: Missing data; potential physiological
      imbalances between groups. CONCLUSIONS: Although overall treatment effects were
      not significant, differences in favor of stimulation were suggested. Barriers to
      observing treatment effects included a decrease in vomiting for both groups
      during session 1, insufficient washout, and the absence of baseline vomiting for
      some patients. Future studies should better define inclusion criteria, use longer
      washout periods, randomize by etiology and baseline physiological findings, and
      pursue alternative designs. ( CLINICAL TRIAL REGISTRATION NUMBER: 00432835.).

PMID- 21872709
TI  - EUS-guided fine-needle tissue acquisition by using a 19-gauge needle in a
      selected patient population: a prospective study.
AB  - BACKGROUND: The ability to obtain tissue samples for histological examination
      during EUS has theoretical advantages over cytology alone. OBJECTIVE: To
      prospectively evaluate the feasibility and yield of EUS-guided fine-needle tissue
      acquisition (EUS-FNTA) with a large-gauge needle in patients in whom we expected
      histology to be more useful than cytology to reach a definitive diagnosis.
      DESIGN: Prospective cohort study. SETTING: Tertiary care academic medical center.
      PATIENTS: Consecutive patients with subepithelial lesions, esophagogastric wall
      thickening, mediastinal and abdominal masses/lymphadenopathy of unknown origin,
      or pancreatic lesions after nondiagnostic FNA. INTERVENTIONS: EUS-FNTA with a 19
      gauge needle. MAIN OUTCOME MEASUREMENTS: Feasibility and yield of EUS-FNTA.
      RESULTS: A total of 120 patients with a mean age of 61 +/- 14.6 years and mean
      lesion size of 38 +/- 25 mm (range 8-140 mm) were enrolled. FNTA was successfully
      performed in all but 1 patient (98.9%), and adequate samples for histological
      examination were obtained in 116 of the 119 patients (97.5%) in whom EUS-FNTA was
      technically successful. A mean of 2.8 +/- 0.8 passes per patient were performed.
      At the time of current follow-up, a definitive diagnosis was available in 117 of
      the 120 patients (97.5%), with only 8 false-negative results. The sensitivity,
      specificity, positive and negative predictive values, and diagnostic accuracy of
      EUS-FNTA in the 117 patients with a definitive diagnosis were 91.8%, 100%, 100%,
      71.4%, and 93.2%, respectively. LIMITATIONS: Single-center study with limited
      power. CONCLUSIONS: EUS-FNTA by using a large-gauge needle has a high yield and
      promising diagnostic accuracy and could be used when histology may be more useful
      than cytology to reach a definitive diagnosis.

PMID- 21872710
TI  - Complex biliary stones: treatment with removable self-expandable metal stents: a
      new approach (with videos).
AB  - BACKGROUND: Complex biliary stones often require temporary stent placement before
      a repeat attempt at extraction. To date, covered self-expandable metal stents
      (CSEMSs) have not been formally investigated for this indication. OBJECTIVE: To
      evaluate the efficacy and safety of CSEMSs in patients with retained complex
      biliary stones. DESIGN: Retrospective case series. SETTING: Large quaternary-care
      center. PATIENTS: Thirty-six patients (24 women) with complex biliary stones with
      incomplete stone clearance after endoscopic retrograde cholangiography (ERC) with
      biliary sphincterotomy. INTERVENTIONS: Patients with incomplete stone clearance
      after ERC with biliary sphincterotomy underwent temporary placement of CSEMSs,
      with subsequent removal before repeat stone extraction. MAIN OUTCOME
      MEASUREMENTS: Success achieving immediate biliary drainage and eventual complete
      duct clearance. Procedure-related complications were also assessed. RESULTS:
      CSEMS placement was successful in establishing immediate biliary drainage in all
      36 patients. Complete duct clearance at repeat ERC was achieved in 29 of 35
      patients after a mean duration of 6.4 weeks. Four of the remaining 6 patients
      underwent sequential CSEMS placement, with eventual duct clearance after multiple
      ERCPs. There were no complications related to biliary obstruction. One patient
      died of a nonbiliary cause. Of the total 42 CSEMSs placed, there were 4 cases
      (9.5%) of clinically insignificant stent migration. LIMITATIONS: Single-center
      experience, retrospective design. CONCLUSIONS: CSEMSs permit management of
      complex biliary stones, but require multiple sessions. The cost-effectiveness of
      this technique needs further investigation.

PMID- 21872711
TI  - A decade of double-balloon enteroscopy: what have we learned?

PMID- 21872712
TI  - Will colon capsule endoscopy replace screening colonoscopy?

PMID- 21872713
TI  - A humanitarian exercise during gastroenterology fellowship.

PMID- 21872714
TI  - Endoscopic visceral fat removal as therapy for obesity and metabolic syndrome: a
      sham-controlled pilot study (with video).
AB  - BACKGROUND: Increased visceral adiposity is a key feature of obesity and
      metabolic syndrome. Previous studies have generated controversial results
      regarding visceral fat (VF) removal as a therapy for obesity and metabolic
      syndrome. OBJECTIVE: To study the effect of surgical VF removal on metabolic
      profiles in a mouse model of diet-induced obesity and metabolic syndrome and to
      evaluate for the first time the feasibility of endoscopic omentectomy using
      natural orifice transluminal endoscopic surgery (NOTES) technique as treatment
      for obesity and metabolic syndrome in a feline model. SETTING: The Johns Hopkins
      Hospital. DESIGN: Sham-controlled study in a mouse model of metabolic syndrome
      and then pilot endoscopic sham-controlled study in cats. INTERVENTIONS: Partial
      or total surgical VF removal was performed in a high-fat diet-induced mouse model
      of obesity and metabolic syndrome, followed by measurements of metabolic
      profiles, and endoscopic omentectomy was performed in a feline model using the
      NOTES approach. MAIN OUTCOME MEASUREMENTS: Weight loss and metabolic profiles.
      RESULTS: In a mouse model of obesity, total but not partial VF removal
      significantly improved obesity and metabolic syndrome, including insulin
      resistance and hepatic steatosis (all P < .05 vs sham surgery). The improved
      metabolic syndrome was associated with significantly decreased inflammatory
      cytokines. In a feline model, endoscopic omentectomy was feasible and safe and
      resulted in a net weight loss compared with sham surgery (-387 +/- 437 g vs 233
      +/- 351 g, P = .1, respectively). LIMITATIONS: Animal experiments. CONCLUSIONS:
      Endoscopic omentectomy is safe and feasible and has the potential to treat
      obesity and metabolic syndrome. Near-total VF removal is required to achieve net
      weight loss and improvement of metabolic syndrome.

PMID- 21872715
TI  - Endoscopic treatment of Zenker's diverticulum by harmonic scalpel.
AB  - BACKGROUND: Zenker's diverticulum (ZD) is a rare condition with a reported
      prevalence of 0.01% to 0.11% in the general population. Endoscopic treatment
      consists of the division of the septum between the diverticulum and the
      esophagus, within which the cricopharyngeal muscle is contained. Diathermic
      monopolar current, argon plasma coagulation, and laser have been used to incise
      the muscular septum with satisfactory results. The main limitation of endoscopic
      treatment is the occurrence of complications. Perforation and hemorrhage are
      reported in as many as 23% and 10% of patients, respectively. OBJECTIVE: The aim
      of this study was to use the technique of endoscopic diverticulotomy by using a
      harmonic scalpel in patients with ZD and to demonstrate the feasibility of using
      flexible and rigid devices in ZD treatment. DESIGN: Case series study. Standard
      protocol was used for patient management, endoscopic procedure, and data
      collection. SETTING: Single endoscopist demonstrating preliminary results.
      PATIENTS: Five patients (4 men; median +/- standard deviation [SD] age 69.6 +/-
      9.06 years, range 59-83 years) with ZD were treated with this technique. All
      patients reported dysphagia and halitosis. The diagnosis was based on clinical,
      endoscopic, and radiographic findings. INTERVENTIONS: All patients received
      general anesthesia and were placed in the left lateral position. A standard
      videogastroscope (9.8 mm) and a stiff guidewire were used to insert and achieve
      an adequate exposure of the ZD septum. The septum was divided using a harmonic
      scalpel under thin endoscope (5.2 mm) visualization through a soft
      diverticuloscope. MAIN OUTCOME MEASUREMENT: Feasibility of an endoscopic
      technique by using rigid and flexible devices to treat ZD. RESULTS: Four patients
      (80%) were successfully treated in 1 session. The median +/- SD size of the
      diverticulum was 3.6 +/- 0.89 cm (range 3-5 cm). Median +/- SD procedure time was
      17.33 +/- 2.33 minutes (range 15-20 minutes) in 6 procedures. No hemorrhage or
      perforation occurred. One patient (20%) required a second session to complete
      dissection of the ZD septum. All patients demonstrated improvement of dysphagia
      score after treatment. LIMITATIONS: Small case series design. CONCLUSIONS:
      Endoscopic treatment of ZD by harmonic scalpel through a soft diverticuloscope
      was feasible and effective in this small case series. Larger studies are
      warranted to further evaluate this technique.

PMID- 21872716
TI  - EUS-guided single-incision needle-knife biopsy: description and results of a new
      method for tissue sampling of subepithelial GI tumors (with video).
AB  - BACKGROUND: The diagnostic efficacy of current tissue sampling techniques for
      upper GI subepithelial tumors (SETs) appears to be limited. Better tissue
      acquisition techniques are needed to improve the diagnostic yield in this
      setting. OBJECTIVE: Our purpose was to determine the safety and diagnostic yield
      of EUS-guided needle-knife incision and forceps biopsy (SINK biopsy) of upper GI
      SETs. DESIGN: Retrospective database review. SETTING: Academic tertiary-care
      referral center. PATIENTS: This study involved 14 consecutive patients referred
      for EUS evaluation of upper GI SETs with previous unsuccessful attempts at tissue
      diagnosis by conventional forceps biopsy. INTERVENTION: EUS-guided needle-knife
      incision and forceps biopsy. MAIN OUTCOME MEASUREMENTS: The safety and diagnostic
      yield of this method, compared with EUS-guided fine-needle aspiration (EUS-FNA),
      when possible. RESULTS: SINK biopsy provided tissue samples that were sufficient
      for definite histologic diagnosis in 13 of 14 cases (diagnostic yield 92.8%).
      There were 8 gastric GI stromal tumors. In 7 of 8, the size of SINK specimens
      allowed immunohistochemical analysis, and the evaluation of malignant potential
      was carried out by means of mitotic index determination in 5 cases (71.42%). SINK
      biopsies determined the pathological diagnosis of all (4 of 4) nonmesenchymal
      lesions. Eight patients underwent both EUS-FNA and SINK, with final histologic
      diagnosis determined in 6 of 8 cases (75%) by SINK versus 1 of 8 cases (12.5%) by
      EUS-FNA (Fisher exact test, P = .023). There were no procedure-related
      complications. LIMITATIONS: A single-center, retrospective analysis with small
      sample size. CONCLUSION: SINK biopsy appears to be an easy, safe, and effective
      technique for determining the definitive pathological diagnosis, evaluation of
      the malignant potential, and planning management of SETs. It could be a reliable
      alternative to conventional FNA, providing larger samples that improve the
      histologic yield.

PMID- 21872717
TI  - EUS-assisted, fluoroscopically guided gastrostomy tube placement in patients with
      Roux-en-Y gastric bypass: a novel technique for access to the gastric remnant.
AB  - BACKGROUND: Access to the excluded gastric remnant in patients after Roux-en-Y
      gastric bypass for gastrostomy tube placement or therapeutic endoscopy is a
      technical challenge. Available techniques include interventional radiology-placed
      gastrostomy, deep enteroscopy, and surgical gastrostomy; however, these
      techniques are hampered by complications, technical complexity, or invasiveness.
      OBJECTIVE: To describe a novel technique that uses EUS to insufflate the excluded
      gastric remnant for fluoroscopically guided percutaneous gastrostomy placement.
      DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Ten patients
      who required gastrostomy placement after Roux-en-Y gastric bypass. INTERVENTIONS:
      EUS was used to puncture the excluded stomach through the gastric pouch or
      jejunum. The stomach was insufflated, and a direct percutaneous gastrostomy
      placed under fluoroscopic guidance in the distended stomach. MAIN OUTCOME
      MEASUREMENTS: Feasibility, safety, and efficacy of EUS-assisted, fluoroscopically
      guided gastrostomy tube placement. RESULTS: Technical success of EUS-assisted
      gastrostomy was achieved in 9 of 10 patients(90%). There were no complications.
      LIMITATIONS: Single-institution study, small sample size. CONCLUSIONS: EUS
      assisted, fluoroscopically guided gastrostomy tube placement may be a safe and
      feasible technique to obtain enteral access to the excluded gastric remnant in
      patients after Roux-en-Y gastric bypass at specialized centers.

PMID- 21872719
TI  - A case of beef tapeworm (Taenia saginata) infection observed by using video
      capsule endoscopy and radiography (with videos).

PMID- 21872718
TI  - Novel application of GI electrical stimulation in Roux stasis syndrome (with
      video).
AB  - BACKGROUND: About one-third of patients undergoing a Roux-en-Y anastomosis
      develop Roux stasis syndrome, likely because of disordered electrical conduction.
      GI electrical stimulation has been previously used successfully in the management
      of postsurgical gastroparesis. OBJECTIVE: Endoscopic placement of temporary
      electrodes and GI electrical stimulation in the management of severe Roux stasis
      syndrome in a patient with esophagojejunostomy and to determine whether the
      patient would be a candidate for surgical permanent electrode placement. DESIGN:
      Case report. SETTING: Academic medical center. PATIENTS: This study involved a
      patient with Roux stasis syndrome. INTERVENTION: Upper endoscopy was performed,
      followed by endoscopic placement of two temporary electrodes, one each in the two
      jejunal limbs. Electrical stimulation was provided by an external stimulation
      device. The patient was re-evaluated 5 days later. MAIN OUTCOME MEASUREMENTS:
      Electrogastrogram (EGG) parameters including frequency, amplitude, and frequency
      amplitude ratio and total symptom score and health-related quality of life score.
      RESULTS: There was a significant improvement in EGG parameters with electrical
      stimulation. Also, the patient had a marked improvement in total GI symptom
      score, from 11 to 4, with a dramatic improvement in the health-related quality of
      life score from -3 to +3. LIMITATIONS: Single case report. CONCLUSION: Endoscopic
      placement of temporary electrodes is feasible and safe. GI electrical stimulation
      of the jejunal limb is a potentially effective treatment for Roux stasis
      syndrome.

PMID- 21872720
TI  - Two polyps on a common stalk.

PMID- 21872721
TI  - The SEDASYS System is not intended for the sedation of high-risk patients.

PMID- 21872722
TI  - Large-balloon dilation after sphincterotomy: anatomical and technical issues.

PMID- 21872724
TI  - Novel use of the Soehendra stent extractor for pancreatic stone lithotripsy.

PMID- 21872725
TI  - Percutaneous endoscopic gastrostomy tube placement should be done when indicated,
      regardless of C-reactive protein and albumin levels.

PMID- 21872726
TI  - Prolonged endoclip retention time.

PMID- 21872728
TI  - Development of distal rectal cancer 5 years after a normal photograph of the
      distal rectum.

PMID- 21872729
TI  - Asthma in the elderly: What we do not know yet but should find out.

PMID- 21872731
TI  - Urgently needed: a framework convention for obesity control.

PMID- 21872732
TI  - Addiction: a complex disorder.

PMID- 21872733
TI  - Sex imbalance in China.

PMID- 21872730
TI  - Asthma in the elderly: Current understanding and future research needs--a report
      of a National Institute on Aging (NIA) workshop.
AB  - Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity
      of knowledge on the subject. The National Institute on Aging convened this
      workshop to identify what is known and what gaps in knowledge remain and suggest
      research directions needed to improve the understanding and care of asthma in the
      elderly. Asthma presenting at an advanced age often has similar clinical and
      physiologic consequences as seen with younger patients, but comorbid illnesses
      and the psychosocial effects of aging might affect the diagnosis, clinical
      presentation, and care of asthma in this population. At least 2 phenotypes exist
      among elderly patients with asthma; those with longstanding asthma have more
      severe airflow limitation and less complete reversibility than those with late
      onset asthma. Many challenges exist in the recognition and treatment of asthma in
      the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the
      elderly are likely to be different from those seen in young asthmatic patients,
      and these differences might influence the clinical course and outcomes of asthma
      in this population.

PMID- 21872734
TI  - The future challenge of obesity.

PMID- 21872735
TI  - Reversing the tide of obesity.

PMID- 21872736
TI  - Where next for obesity?

PMID- 21872738
TI  - Boyd Swinburn: combating obesity at the community level.

PMID- 21872740
TI  - Chemotherapy for older patients with colorectal cancer.

PMID- 21872741
TI  - Chemotherapy for older patients with colorectal cancer.

PMID- 21872742
TI  - The Mediterranean diet: a cultural journey.

PMID- 21872743
TI  - Changes in alcohol metabolism after gastric bypass surgery.

PMID- 21872745
TI  - Continued neglect of ageing of HIV epidemic at UN meeting.

PMID- 21872746
TI  - Further analyses of the Myeloma IX Study.

PMID- 21872747
TI  - China's first rare-disease registry is under development.

PMID- 21872748
TI  - UK Royal Colleges and health service reform.

PMID- 21872749
TI  - The global obesity pandemic: shaped by global drivers and local environments.
AB  - The simultaneous increases in obesity in almost all countries seem to be driven
      mainly by changes in the global food system, which is producing more processed,
      affordable, and effectively marketed food than ever before. This passive
      overconsumption of energy leading to obesity is a predictable outcome of market
      economies predicated on consumption-based growth. The global food system drivers
      interact with local environmental factors to create a wide variation in obesity
      prevalence between populations. Within populations, the interactions between
      environmental and individual factors, including genetic makeup, explain
      variability in body size between individuals. However, even with this individual
      variation, the epidemic has predictable patterns in subpopulations. In low-income
      countries, obesity mostly affects middle-aged adults (especially women) from
      wealthy, urban environments; whereas in high-income countries it affects both
      sexes and all ages, but is disproportionately greater in disadvantaged groups.
      Unlike other major causes of preventable death and disability, such as tobacco
      use, injuries, and infectious diseases, there are no exemplar populations in
      which the obesity epidemic has been reversed by public health measures. This
      absence increases the urgency for evidence-creating policy action, with a
      priority on reduction of the supply-side drivers.

PMID- 21872750
TI  - Health and economic burden of the projected obesity trends in the USA and the UK.
AB  - Rising prevalence of obesity is a worldwide health concern because excess weight
      gain within populations forecasts an increased burden from several diseases, most
      notably cardiovascular diseases, diabetes, and cancers. In this report, we used a
      simulation model to project the probable health and economic consequences in the
      next two decades from a continued rise in obesity in two ageing populations--the
      USA and the UK. These trends project 65 million more obese adults in the USA and
      11 million more obese adults in the UK by 2030, consequently accruing an
      additional 6-8.5 million cases of diabetes, 5.7-7.3 million cases of heart
      disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million
      quality-adjusted life years forgone for USA and UK combined. The combined medical
      costs associated with treatment of these preventable diseases are estimated to
      increase by $48-66 billion/year in the USA and by L1.9-2 billion/year in the UK
      by 2030. Hence, effective policies to promote healthier weight also have economic
      benefits.

PMID- 21872751
TI  - Quantification of the effect of energy imbalance on bodyweight.
AB  - Obesity interventions can result in weight loss, but accurate prediction of the
      bodyweight time course requires properly accounting for dynamic energy
      imbalances. In this report, we describe a mathematical modelling approach to
      adult human metabolism that simulates energy expenditure adaptations during
      weight loss. We also present a web-based simulator for prediction of weight
      change dynamics. We show that the bodyweight response to a change of energy
      intake is slow, with half times of about 1 year. Furthermore, adults with greater
      adiposity have a larger expected weight loss for the same change of energy
      intake, and to reach their steady-state weight will take longer than it would for
      those with less initial body fat. Using a population-averaged model, we
      calculated the energy-balance dynamics corresponding to the development of the US
      adult obesity epidemic. A small persistent average daily energy imbalance gap
      between intake and expenditure of about 30 kJ per day underlies the observed
      average weight gain. However, energy intake must have risen to keep pace with
      increased expenditure associated with increased weight. The average increase of
      energy intake needed to sustain the increased weight (the maintenance energy gap)
      has amounted to about 0.9 MJ per day and quantifies the public health challenge
      to reverse the obesity epidemic.

PMID- 21872752
TI  - Changing the future of obesity: science, policy, and action.
AB  - The global obesity epidemic has been escalating for four decades, yet sustained
      prevention efforts have barely begun. An emerging science that uses quantitative
      models has provided key insights into the dynamics of this epidemic, and enabled
      researchers to combine evidence and to calculate the effect of behaviours,
      interventions, and policies at several levels--from individual to population.
      Forecasts suggest that high rates of obesity will affect future population health
      and economics. Energy gap models have quantified the association of changes in
      energy intake and expenditure with weight change, and have documented the effect
      of higher intake on obesity prevalence. Empirical evidence that shows
      interventions are effective is limited but expanding. We identify several cost
      effective policies that governments should prioritise for implementation. Systems
      science provides a framework for organising the complexity of forces driving the
      obesity epidemic and has important implications for policy makers. Many parties
      (such as governments, international organisations, the private sector, and civil
      society) need to contribute complementary actions in a coordinated approach.
      Priority actions include policies to improve the food and built environments,
      cross-cutting actions (such as leadership, healthy public policies, and
      monitoring), and much greater funding for prevention programmes. Increased
      investment in population obesity monitoring would improve the accuracy of
      forecasts and evaluations. The integration of actions within existing systems
      into both health and non-health sectors (trade, agriculture, transport, urban
      planning, and development) can greatly increase the influence and sustainability
      of policies. We call for a sustained worldwide effort to monitor, prevent, and
      control obesity.

PMID- 21872753
TI  - Lumbar puncture in paediatric stroke.

PMID- 21872754
TI  - Preface: A window into the reproductive era research.

PMID- 21872755
TI  - Cell-based therapies in orthopedics.

PMID- 21872756
TI  - Embryonic stem cells and iPS cells: sources and characteristics.
AB  - The field of regenerative medicine research is rapidly expanding. One area of
      interest to equine researchers is the possibility of isolating or generating
      pluripotent cells, capable of producing differentiated cell types derived from
      all 3 primary germ layers. Reports of equine embryonic stem-like (ES) cell
      isolation can be found in the literature. Other groups are working to produce
      equine-induced pluripotent stem (iPS) cells. This article summarizes the
      essential features needed to characterize a cell type as pluripotent, specific
      challenges in using the horse as a model organism for pluripotent cell
      generation, and current and upcoming clinical trials using ES/iPS cells.

PMID- 21872757
TI  - Mesenchymal stem cells: characteristics, sources, and mechanisms of action.
AB  - This article provides an overview of mesenchymal stem cell (MSC) biology. In the
      first section, the characteristics that are routinely used to define MSCs
      adherence, proliferation, multi-lineage potential, and "cluster of
      differentiation" marker profiles-are discussed. In the second section, the major
      tissues and body fluids that are used as sources for equine MSCs are presented,
      along with the comparative biologic activities of MSCs from specific locations.
      Finally, the current understanding of the mechanisms by which MSCs influence
      repair and regeneration are discussed, with an emphasis on the clinical
      importance of MSC trophic activities.

PMID- 21872758
TI  - Collection and propagation methods for mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSC) are derived from adult mesenchymal tissues and
      have the ability to undergo differentiation into bone, cartilage, and fat, and
      have therefore attracted great interest in regenerative medicine. Many isolation
      and culture methods have been described, making comparison between laboratories
      and quality-control protocols difficult. A uniform protocol to characterize
      equine MSC has recently been proposed, aiming to introduce consistency across the
      equine stem cell research field. This article reviews the published techniques
      for collection and propagation of equine MSC, focusing on bone marrow-derived and
      adipose-derived cells.

PMID- 21872759
TI  - Autologous biologic treatment for equine musculoskeletal injuries: platelet-rich
      plasma and IL-1 receptor antagonist protein.
AB  - Autologous biologic therapies such as platelet-rich plasma and autologous
      conditioned serum are in widespread clinical use to treat musculoskeletal
      pathology in horses. These substances exert a therapeutic effect through the
      provision of either anabolic or anti-catabolic factors, or a combination of both.
      This article discusses the history, experimental and clinical literature, and
      currently accepted preparation and usage strategies for both platelet-rich plasma
      and autologous conditioned serum.

PMID- 21872760
TI  - Stem cell-based therapies for bone repair.
AB  - This article provides an overview of the cellular and molecular events involved
      in bone repair and the current approaches to using stem cells as an adjunct to
      this process. The article emphasizes the key role of osteoprogenitor cells in the
      formation of bone and where the clinical applications of current research may
      lend themselves to large animal orthopaedics. The processes involved in
      osteogenic differentiation are presented and strategies for bone formation,
      including induction by osteogenic factors, bioscaffolds, and gene therapy, are
      reviewed.

PMID- 21872761
TI  - Cell-based therapies for tendon and ligament injuries.
AB  - Tendon and ligament injuries have proved difficult to treat effectively. Cell
      based therapies offer the potential to harness the complex protein synthetic
      machinery of the cell to induce a regenerative response rather than fibrous
      scarring. This article reviews the current state of play with respect to the
      clinically used cell preparations for the treatment of tendon and ligaments
      overstrain injuries.

PMID- 21872762
TI  - Cell-based therapies for equine joint disease.
AB  - Joint disease is a major cause of wastage in performance horses. Arthritis can be
      challenging to treat because articular cartilage has little or no capacity for
      repair, therapeutic options are limited and are largely targeted at ameliorating
      clinical signs of joint disease. Cell-based therapies have potential to overcome
      the intrinsic constraints to articular cartilage repair. This article focuses on
      cell-based therapies for treatment of equine joint disease. Results from
      experimental model and human clinical studies are presented along with available
      data from equine studies.

PMID- 21872763
TI  - Anti-inflammatory and immunomodulatory activities of stem cells.
AB  - The recent interest in equine stem cell biology and the rapid increase in
      experimental data highlight the growing attention that this topic has been
      receiving over the past few years. Within the field of stem cell biology, the
      relevance of immunobiology is of particular intrigue. It appears that optimal and
      effective stem cell therapy for equine patients will require a thorough analysis
      of the immune properties of stem cells as well as their response to immune
      mediators. The main goal of this review is to discuss the biology of adult
      mesenchymal stem cells in the context of immunology.

PMID- 21872764
TI  - Commercial cell-based therapies for musculoskeletal injuries in horses.
AB  - Several cell-based therapeutic options to treat musculoskeletal injuries in
      horses are commercially available. The current literature supports the use of
      cell-based therapies to treat equine musculoskeletal injuries. Researchers
      continue to search for more effective cell-based therapies to provide
      practitioners with optimal treatment tools for musculoskeletal injuries in
      horses. Cell-based therapies require specialized facilities and technical
      competencies that might not be available or economically justifiable in many
      private practices. This review provides a summary of current commercially
      available cell-based therapeutic products for equine applications, their
      similarities and differences, and current objective data relating to their
      clinical efficacy.

PMID- 21872765
TI  - Evidence-based medicine and stem cell therapy: how do we know such technologies
      are safe and efficacious?
AB  - Evidence-based medicine (EBM) refers to the conscientious, explicit, and
      judicious use of current best evidence from research for the care of an
      individual patient. Central to the adoption of EBM is both producing and
      identifying the best possible evidence for a particular intervention or therapy.
      This article identifies and reviews the approaches to producing and identifying
      the best possible evidence that is necessary for the full acceptance of stem cell
      therapies in the horse and reviews the approaches that will allow future clinical
      studies in stem cell therapies to provide the best evidence for determining
      efficacy.

PMID- 21872766
TI  - The regulation of veterinary regenerative medicine and the potential impact of
      such regulation on clinicians and firms commercializing these treatments.
AB  - This article provides an overview of the US Food and Drug Administration's
      current and potential regulation of veterinary regenerative medicine and the
      various products used in the practice. This article also discusses several of the
      potential enforcement risks associated with the commercialization of such
      therapies and products and offers the reader strategies for mitigating those
      risks. Finally, the article concludes with a review of an important and ongoing
      court battle that focuses on the marketing and promotion of cellular-based
      therapies for humans that could have a significant impact on the regulation of
      both human and veterinary products.

PMID- 21872767
TI  - Cell-based therapies: current issues and future directions.
AB  - This article focuses on current issues facing cell-based therapies in equine
      practice and future studies validating the use of stem cells and related biologic
      therapies for the treatment of musculoskeletal conditions in the horse. Issues
      raised include the characterization and use of tissue- and anatomic location
      specific mesenchymal stem cell (MSC) sources, the putative advantages and
      feasibility of allogeneic embryonic stem cell and MSC products, the technical
      advantages and performance of cell-based biologic agents that do not require
      extensive ex vivo manipulation, the regulation of MSC homing, potential
      nonorthopaedic stem cell applications, and the logistics required to demonstrate
      cell-based therapy efficacy in horses.

PMID- 21872768
TI  - Functionalized ionic liquid modified mesoporous silica SBA-15: a novel,
      designable and efficient carrier for porcine pancreas lipase.
AB  - A series of functionalized ionic liquid modified mesoporous silicas SBA-15 (FIL
      SBA) were synthesized by modulating the loading and cation/anion ratio of the
      functionalized ionic liquid (FIL). The prepared materials FIL-SBA were used as a
      novel carrier system to immobilize porcine pancreas lipase (PPL). Enzymatic
      activity and reusability of the immobilized enzyme were investigated using the
      triacetin hydrolysis reaction. The combined advantages of the nano-sized pore
      diameter, large surface area and high pore volume of SBA-15, and the tunable
      properties of the FIL for enzymes immobilized in FIL-SBA gave a maximum
      improvement of 570% in relative activity, with 63% retention of initial activity
      after five cycles of use. Carriers and immobilized enzymes were characterized
      using nitrogen adsorption, small-angle X-ray diffraction (SXRD), Fourier
      transform infrared (FT-IR), elemental analysis, nuclear magnetic resonance (NMR),
      scanning and transmission electron microscopy (SEM and TEM). It was shown that
      the introduction of FIL influenced the catalytic behavior of PPL significantly by
      changing the structure and surface properties of the carriers.

PMID- 21872770
TI  - Endometriosis in adolescents: a whole different focus.

PMID- 21872769
TI  - Immunoaging induced by hematopoietic stem cell aging.
AB  - Hematopoietic stem cells (HSCs) generate all known hematopoietic lineages and
      self-renew, but the function of HSCs declines during aging, which is
      characterized as impairments of lymphopoiesis and enhanced myelopoiesis. These
      aging-associated changes correlate with an increasing risk of myelo-proliferative
      diseases and impairments in immune function. Recent studies showed that only a
      subpopulation of HSCs contains a high capacity to undergo lymphoid
      differentiation but this subpopulation is lost during aging, which contributes to
      age-related impairments in lymphopoiesis. On the basis of the observations that
      DNA damage and telomere dysfunction can impair stem cell function, it is possible
      that accumulation of DNA damage results in the loss of subpopulations of HSCs
      that are required for the maintenance of lymphopoiesis and immune functions
      during aging.

PMID- 21872771
TI  - Ambiguous genitalia - disorders of sexual differentiation.

PMID- 21872772
TI  - Congenital adrenal hyperplasia and ambiguous genitalia.

PMID- 21872773
TI  - Ambiguous genitalia in the newborn: an overview and teaching tool.
AB  - Ambiguous genitalia is a significant example of a disorder of sexual development,
      in which the external genitalia do not have the typical appearance of either sex.
      Although the birth of a child with ambiguous genitalia is rare, the emergent
      nature of the issue demands that healthcare providers have at least a familiarity
      with the underlying etiologies, the issues, and the initial approach to diagnosis
      and management. With numerous etiologies, potential difficulties with reaching a
      diagnosis, and many challenges with immediate and long-term care, the topic of
      ambiguous genitalia can be daunting. We provide a review of basic embryology, as
      well as a classification system for understanding the various etiological causes
      of ambiguous genitalia. The important clinical aspects of diagnosis and
      management are also highlighted, and a teaching tool has been included to help
      the reader (or their learners) to solidify information presented. Our overall
      goal is to provide practical information on ambiguous genitalia and allow the
      clinician to apply this information to clinically relevant scenarios.

PMID- 21872774
TI  - Premenstrual syndrome: the experience from a sample of Sri Lankan adolescents.
AB  - SETTING: Government schools of Colombo. MAIN OUTCOME MEASURES: Premenstrual
      symptomatology (PMS) was determined by a modified version of Premenstrual Symptom
      screening tool and American College of Obstetricians and Gynecologists (ACOG)
      diagnostic criteria were used in categorizing study units as having PMS. Other
      outcome measures were demographic and reproductive factors thought to be
      correlates of PMS, health seeking behavior for premenstrual symptoms, and how
      premenstrual symptoms impact their daily life. RESULTS: Individual premenstrual
      symptoms were experienced by 65.7% of the population. The most common somatic
      symptom was fatigue (29.9%) and affective symptom was feeling sad/hopeless
      (29.6%). Prevalence of PMS was 8.75% (95%CI: 6.43-11.07). Multivariate analysis
      revealed the presence of: chronic physical illness (P = 0.001); dysmenorrhea (P <
      0.0001), and regular menstrual cycles (P = 0.006) as correlates of PMS. Presence
      of PMS significantly disturbed "in school" activities, relationships and daily
      routines (P < 0.005) indicating a high negative influence on adolescents' daily
      life. Only 9.7% sought help from (western) medical practitioners for their
      premenstrual symptoms and a majority has not perceived it as a condition to
      report. CONCLUSION: Premenstrual syndrome is a common condition among adolescent
      schoolgirls with a high negative influence on their daily life. The health care
      seeking behavior is poor, indicating the necessity to address the subject at
      adolescent reproductive health programs.

PMID- 21872775
TI  - Female adolescent athletes' awareness of the connection between menstrual status
      and bone health.
AB  - STUDY OBJECTIVE: The aims of this study are to determine among female high school
      track athletes: (1) knowledge of the association between menstrual irregularity
      and bone health; (2) attitudes toward amenorrhea, specifically if amenorrhea is
      seen as a sign of athletic success; (3) the association between knowledge and
      attitudes based on athlete menstrual status. DESIGN: Cross-sectional survey.
      SETTING: Five public high schools in Texas. PARTICIPANTS: 103 female high school
      track athletes ages 14-18 years. INTERVENTION: Participants completed a
      questionnaire that addressed menstrual history, details of track participation,
      knowledge of bone mineral density (BMD)/ menstrual status connection, and
      attitudes about the desirability of oligo/amenorrhea. OUTCOME MEASURES:
      Frequencies of attitude and knowledge replies, summative knowledge score, and
      correlations between attitudes, knowledge, and menstrual status. RESULTS: Sixteen
      subjects (16.7%) met criteria for amenorrhea, 16 for oligomenorrhea (16.7%).
      Median summative knowledge score was one of six. Menstrual irregularity was
      associated with lower knowledge (P = 0.035). Incorrect answers about consequences
      of bone loss and the link to menstrual irregularity were given by >=90% of
      respondents. Lower knowledge was associated with a greater number of "don't know"
      replies to attitude questions (P = 0.002). Among more knowledgeable participants
      endorsing opinions, menstrual irregularity was not seen as a sign of athletic
      success. CONCLUSIONS: The prevalence of irregular menses is high among adolescent
      track athletes and a larger-scale inquiry to clarify adolescent athletes'
      knowledge of and attitudes about the link between menstrual patterns and BMD is
      indicated. Education may provide one key to improved health behavior among this
      at-risk population.

PMID- 21872776
TI  - MRSA: rare in the vagina.
AB  - STUDY OBJECTIVE: To determine the prevalence of vaginal Staphylococcus aureus and
      methicillin-resistant S. aureus (MRSA) in sexually active adolescent women.
      DESIGN: A prospective surveillance study. PARTICIPANTS: Patients included 315
      sexually active young women (ages 13-24) undergoing routine pelvic examination
      and wet mount testing in an urban teen health center. MAIN OUTCOME MEASURES:
      Prevalence of vaginal S. aureus and MRSA. RESULTS: S. aureus was present in 16
      samples for a point estimate of 5.1% (95% CI: 2.6%-7.5%). MRSA was detected in
      two samples, giving a vaginal prevalence estimate of 0.6% (95% CI: 0.0% -1.5%).
      No differences were detected in the prevalence of S. aureus by age or race,
      although no cases of S. aureus were observed in those under age 15. CONCLUSION:
      The prevalence of MRSA in a sample of sexually active adolescents was as rare as
      reported in other populations. It is unlikely that vaginal MRSA is a reservoir
      for community acquired infections.

PMID- 21872777
TI  - Adolescent users of an online contraception selection tool: how user preferences
      and characteristics differ from those of adults.
AB  - STUDY OBJECTIVE: The objective of this study was to report user statistics of an
      online contraception selection tool over a 6-month period, comparing preferences
      and characteristics of adolescents to those of adults. SETTING: Choosing Wisely,
      available on the website www.SexualityandU.ca, is an interactive program that
      helps women select an ideal birth control method. DESIGN: Answers to the online
      questionnaire were logged for a 6-month period. Answers of adolescent users were
      retrospectively reviewed for responses to questions regarding personal
      preferences and compared with those of adults. PARTICIPANTS: Participants of the
      study included users who self-identified as first-time users of Choosing Wisely.
      RESULTS: 3178 adolescents (age <=19) and 4206 adults self-identified as new users
      and completed the software module. Adolescents less commonly reported weighing
      over 198 pounds or to be smokers. 61% of adolescents would prefer to avoid menses
      (vs 52% of adults) and 83% of adolescent would find a pregnancy devastating (vs
      64% of adults). 1720 (54%) of the adolescents had menstrual complaints; of these
      500 (29%) did not believe they could reliably take a pill daily. The majority of
      both adolescents (73%) and adults (71%) claimed to be willing to use a
      contraceptive method that required interruption of intercourse. CONCLUSIONS:
      Choosing Wisely is attracting large numbers of teens and adults, whose responses
      provide insight into the characteristics of those seeking contraception. Our data
      corroborate the need for contraceptive options such as combined contraceptives
      that do not require daily pill-taking and contraceptives that offer menstrual
      management. However, the magnitude of these statistically significant differences
      was not always as impressive clinically.

PMID- 21872778
TI  - Zoonoses, public health, and the exotic animal practitioner.

PMID- 21872779
TI  - One health: zoonoses in the exotic animal practice.
AB  - Zoonoses make up approximately 3/4 of today's emerging infectious diseases; many
      of these zoonoses come from exotic pets and wildlife. Recent outbreaks in humans
      associated with nondomestic animals include Sudden Acute Respiratory Syndrome,
      Ebola virus, salmonellosis, and monkeypox. Expanding human populations, increased
      exotic pet ownership and changes in climate may contribute to increased incidence
      of zoonoses. Education and preventive medicine practices can be applied by
      veterinarians and other health professionals to reduce the risk of contracting a
      zoonotic disease. The health of humans, animals, and the environment must be
      treated as a whole to prevent the transmission of zoonoses.

PMID- 21872780
TI  - Zoonoses associated with fish.
AB  - The taxonomic group that composes the fishes is the most diverse group of
      vertebrates worldwide. The challenges of unique physiologies, a foreign
      environment, and many unknowns attract a passionate group of biologists and
      veterinarians. Economically, fishes have become vital as food, bait, and
      companion animals. Fishermen and fish handlers (processing plants) represent the
      historical human population exposed to fish zoonoses, but growth in aquaculture
      and aquarium hobbyists have led to an increase in published fish-borne zoonotic
      cases starting in the late 1950s that bloomed in the 1980s. Human physicians,
      particularly dermatologists and infectious disease specialists, are now more
      aware of fish-borne zoonoses, but they can be assisted with diagnosis when
      informed patients give more detailed histories with fish/water exposure.

PMID- 21872781
TI  - Zoonotic diseases associated with reptiles and amphibians: an update.
AB  - Reptiles and amphibians are popular as pets. There are increased concerns among
      public health officials because of the zoonotic potential associated with these
      animals. Encounters with reptiles and amphibians are also on the rise in the
      laboratory setting and with wild animals; in both of these practices, there is
      also an increased likelihood for exposure to zoonotic pathogens. It is important
      that veterinarians remain current with the literature as it relates to emerging
      and reemerging zoonotic diseases attributed to reptiles and amphibians so that
      they can protect themselves, their staff, and their clients from potential
      problems.

PMID- 21872782
TI  - Zoonotic diseases of common pet birds: psittacine, passerine, and columbiform
      species.
AB  - Zoonotic transmission of disease from pet birds is uncommon, but there are some
      recognized dangers. Most notably, Chlamydophila psittaci can be transmitted from
      pet birds to humans. Allergic responses to pet birds, including pneumonitis and
      contact dermatitis, have also been documented. Bite wounds from pet birds are
      rarely reported but can cause trauma and develop infection. The other diseases
      discussed here are considered potential zoonotic diseases of pet birds because of
      either isolated reports of suspected but unconfirmed transmission to humans or
      from reports of wild conspecifics being reported to have the disease.

PMID- 21872783
TI  - Zoonoses, public health, and the backyard poultry flock.
AB  - Raising a small flock of poultry for eggs, meat, and possibly companionship is
      becoming an increasingly popular hobby in the United States. Domestic chickens
      (Gallus gallus, forma domestica), turkeys (Meleagris gallopavo, forma domestica),
      and members of the family Anatidae including ducks, geese, and swans are commonly
      kept in these privately owned backyard flocks. Multiple bacterial, viral, fungal,
      and parasitic diseases which affect poultry are known zoonotic pathogens. This
      article reviews these zoonoses and gives recommendations for flock biosecurity,
      as well as for prevention of infection in both birds and humans. Diseases
      associated with other gallinaceous birds are only selectively discussed.

PMID- 21872784
TI  - Public health concerns associated with care of free-living birds.
AB  - Free-living birds are not only susceptible to certain infectious diseases; wild
      bird populations serve as reservoirs of several important diseases of public
      health concern. Bacterial and viral diseases endemic in populations of free
      living birds such as tuberculosis, avian influenza, arboviral infections, and
      enteropathogens have been classified as emerging or reemerging. Providing care to
      wild avian patients increases the opportunity for direct contact with infected
      birds and the possibility of transmission of infectious disease to human
      handlers. Awareness of disease potential is critical to disease monitoring of
      wild populations and will allow for the implementation of precautionary measures
      when working with wild avian species. Biosecurity measures designed to minimize
      risk must be evaluated by individual facilities.

PMID- 21872785
TI  - Rabies epidemiology, risk assessment, and pre- and post exposure vaccination.
AB  - Rabies should always be considered in the differential diagnosis of a neurologic
      disease in a mammal with an unknown vaccination status. Public health
      veterinarians are available to assist in risk assessment as well as coordination
      of animal testing. This article discusses the pathogenesis of rabies and clinical
      presentation in several domestic species. Prevention, North American prevalence
      and distribution, exposure considerations, and post-exposure prophylaxis are also
      discussed. Veterinarians in private practice have an integral role in protection
      of people and domestic animals against rabies.

PMID- 21872786
TI  - Zoonoses of rabbits and rodents.
AB  - Millions of households in the US own rabbits or rodents, including hamsters,
      guinea pigs, and gerbils. Activities such as hunting and camping also involve
      human interactions with wild rabbits and rodents. In many environments, feral
      rabbits and rodents live in close proximity to humans, domesticated animals, and
      other wildlife. Education of rodent and rabbit owners and individuals with
      occupational or recreational exposures to these species is paramount to reduce
      the prevalence of zoonoses associated with rabbit and rodent exposure.

PMID- 21872787
TI  - Zoonoses of ferrets, hedgehogs, and sugar gliders.
AB  - With urbanization, people live in close proximity to their pets. People often
      share their living quarters and furniture, and this proximity carries a new
      potential for pathogen transmission. In addition to the change in lifestyle with
      our pets, new exotic pets are being introduced to the pet industry regularly.
      Often, we are unfamiliar with specific clinical signs of diseases in these new
      exotic pets or the routes of transmission of pathogens for the particular
      species. This article reviews zoonoses that occur naturally in ferrets,
      hedgehogs, and sugar gliders, discussing the occurrence and clinical symptoms of
      these diseases in humans.

PMID- 21872788
TI  - Zoonoses of procyonids and nondomestic felids.
AB  - There are several important zoonotic diseases which can be acquired from
      procyonids, and nondomestic felids. Baylisascaris procyonis, the raccoon
      roundworm, is a common parasite of raccoons and can cause visceral, ocular, or
      neural larval migrans in people. Neural larval migrans can cause severe signs in
      individuals. Dermatophytosis and enteric pathogens are the most important
      zoonotic agents found in nondomestic felids. Microsporum canis infections can be
      spread from nondomestic felids to owners and veterinarians. Toxoplasma gondii can
      be potentially shed by infected felids, and human infections occurring during
      pregnancy can cause blindness in the fetus.

PMID- 21872789
TI  - Zoonotic diseases of primates.
AB  - A zoonotic disease is transmissible from vertebrate animals to humans. This
      article focuses on pertinent zoonotic diseases that have to be taken into
      consideration when working with nonhuman primate (NHP) species. Many factors may
      influence the occurrence of these diseases. Human and NHPs share many
      similarities, not only anatomically but also physiologically. NHP are valuable
      models for many human infectious diseases; therefore, staff can be exposed to
      many potential pathogens. In general, the disease state of a primate can range
      from asymptomatic carrier to death from infection.

PMID- 21872790
TI  - Anemia of renal disease: what it is, what to do and what's new.
AB  - PATIENT GROUP: It is estimated that 15-30% of geriatric cats will develop chronic
      kidney disease (CKD), and that 30-65% of these cats will develop anemia as their
      renal disease worsens. Anemia of renal disease is multifactorial in its
      pathogenesis, but the main cause is reduced production of erythropoietin, a renal
      hormone that controls the bone marrow's production of red blood cells, as kidney
      disease progresses. PRACTICAL RELEVANCE: It is important to recognize the
      presence of anemia of renal disease so that adequate treatment may be instituted
      to improve quality of life and metabolic function. Erythrocyte-stimulating agents
      (ESAs), such as epoetin alfa, epoetin beta and darbepoetin alfa, have been
      developed to counteract the effects of decreased erythropoietin production by the
      kidneys. These treatments, which are the focus of this review, have 83%
      similarity in amino acid sequence to the feline hormone. On average, the target
      packed cell volume (>25%) is reached within 3-4 weeks of ESA therapy. CLINICAL
      CHALLENGES: The use of ESAs has been associated with a number of complications,
      such as iron deficiency, hypertension, arthralgia, fever, seizures, polycythemia
      and pure red cell aplasia (PRCA). Darbepoetin has a prolonged half-life compared
      with epoetin and thus can be given only once a week, instead of three times a
      week. The incidence of PRCA appears to be decreased with darbepoetin use when
      compared with epoetin use in cats. EVIDENCE BASE: There is limited published
      evidence to date to underpin the use of ESAs in cats. This review draws on the
      relevant publications that currently exist, and the authors' personal experience
      of using these therapies for over 5 years.

PMID- 21872791
TI  - Primary hyperaldosteronism: expanding the diagnostic net.
AB  - PRACTICAL RELEVANCE: Primary hyperaldosteronism is probably the most common
      adrenocortical disorder in cats. As in humans, it is often unrecognised, which
      excludes a potentially large number of cats from appropriate treatment. PATIENT
      GROUP: Affected cats present at a median age of 13 years (range 5-20 years). A
      breed or sex predilection has not been documented. The excessive secretion of
      mineralocorticoids usually leads to hypokalaemia and/or systemic arterial
      hypertension. Most affected cats present with muscular weakness and/or ocular
      signs of arterial hypertension. DIAGNOSTICS: In any cat presenting with
      hypokalaemia and/or arterial hypertension, other potential causes should be
      excluded. The ratio of plasma aldosterone concentration to plasma renin activity
      (aldosterone:renin ratio) is currently the best screening test for feline primary
      hyperaldosteronism. Diagnostic imaging is required to differentiate between
      adrenocortical neoplasia and bilateral hyperplasia, and to detect any distant
      metastases. CLINICAL CHALLENGES: The differentiation between adrenocortical
      neoplasia and bilateral hyperplasia is imperative for planning optimal therapy,
      but the limited sensitivity of diagnostic imaging may occasionally pose a
      problem. For confirmed unilateral primary hyperaldosteronism, unilateral
      adrenalectomy is the treatment of choice, and offers an excellent prognosis, but
      potentially fatal intra- and postoperative haemorrhage is a reported complication
      and risk factors have yet to be identified. EVIDENCE BASE: Only a few case
      reports are available on which to base the optimal diagnostic and therapeutic
      approach to feline primary hyperaldosteronism. This article reviews the
      physiology of aldosterone production and the pathophysiology of primary
      hyperaldosteronism, and summarises the currently available literature on the
      feline disease. Practical suggestions are given for the diagnostic investigation
      of cats with suspected primary hyperaldosteronism.

PMID- 21872792
TI  - Cats and calcium oxalate: strategies for managing lower and upper tract stone
      disease.
AB  - PRACTICAL RELEVANCE: Calcium oxalate (CaOx) containing stones are among the most
      common of the urinary tract stones identified in cats. RISK FACTORS: Risk factors
      for CaOx stone formation include such things as breed, gender and diet; stress
      and obesity have also been hypothesized to be risk factors for this disease.
      MANAGEMENT APPROACH: A tailored, individual management strategy for preventing
      CaOx stone recurrence is important and should include addressing the diet,
      environment and any other comorbid conditions present. Increasing the cat's
      moisture intake is one of the key mechanisms for preventing recurrence. CLINICAL
      CHALLENGES: CaOx ureterolithiasis has emerged as a difficult and sometimes life
      threatening problem for cats. In those cats where stones are found incidentally,
      periodic monitoring may be required to assess for disease progression.
      Interventional procedures such as ureteral stent placements are now increasingly
      being performed for recurrent cases or those with larger stone burdens. Periodic
      radiographs for more severe cases and frequent client communication can help
      ensure successful outcomes for cats with lower and upper CaOx stone disease.
      EVIDENCE BASE: Limited evidence-based studies are published regarding management
      of feline upper and lower urinary tract CaOx stone disease, making this a
      difficult condition to manage in some cats. Studies designed to evaluate the
      relationship to dietary modifications, medical management, stress, obesity and
      surgical techniques are warranted in cats with upper and lower urinary tract CaOx
      stones.

PMID- 21872793
TI  - Managing cats with cancer: An examination of ethical perspectives.
AB  - ETHICAL ISSUES: Caring for cancer patients presents many ethical issues for
      veterinarians and other veterinary health workers. The issues that most
      veterinarians think of relate to management of the patient when the owners'
      preferences for treatment do not appear to be in the animal's best interest, as
      well as concerns about toxicities and about costs of veterinary services
      (advanced imaging, surgery, radiation therapy and chemotherapy). While not
      limited to the veterinary profession, we are more often faced with dilemmas about
      the appropriateness of palliative care and decisions about euthanasia than our
      medical colleagues. Equally important are the ethics of not treating patients,
      and the integration of unproven and alternative strategies into conventional
      care. A separate ethical issue arises from investigational therapies and
      research. Less often considered, but nonetheless relevant, are the ethics of
      suboptimal evaluation (staging) of patients prior to treatment, or of not
      informing owners about all the options available. CLIENT COMMUNICATION: Ethical
      veterinary care is intertwined with good client communication. Without good
      communication, it is impossible, for example, to gain informed consent; and
      without informed consent, the ethics of cancer treatment are uncertain. GOAL:
      This article, which draws in part on published research, where stated, and
      otherwise on the author's personal experiences/opinions and those of veterinary
      colleagues, is intended to provoke further thought and discussion on the ethics
      of caring for our cancer patients.

PMID- 21872794
TI  - Brain abscess in seven cats due to a bite wound: MRI findings, surgical
      management and outcome.
AB  - PRESENTATION AND LESION LOCALISATION: Seven adult domestic shorthair cats were
      presented with a 1- to 6-day history of progressive neurological signs. A focal
      skin puncture and subcutaneous swelling over the dorsal part of the head were
      detected on physical examination. Neurological examination indicated lesion(s) in
      the right forebrain in four cats, multifocal forebrain in one cat, left forebrain
      in one cat, and multifocal forebrain and brainstem in the remaining cat. In all
      cats, magnetic resonance imaging revealed a space-occupying forebrain lesion
      causing a severe mass effect on adjacent brain parenchyma. CLINICAL APPROACH AND
      OUTCOME: All cats were managed with a combination of medical and surgical
      treatment. At surgery a small penetrating calvarial fracture was detected in all
      cats, and a tooth fragment was found within the content of the abscess in two
      cats. The combination of surgical intervention, intensive care and intravenous
      antimicrobials led to a return to normal neurological function in five cats.
      PRACTICAL RELEVANCE: As this series of cases indicates, successful resolution of
      a brain abscess due to a bite injury depends on early recognition and combined
      used of antimicrobials and surgical intervention. A particular aim of surgery is
      to remove any skull and foreign body (tooth) fragments that may represent a
      continuing focus of infection.

PMID- 21872797
TI  - Vitamin D receptor (VDR)-mediated actions of 1alpha,25(OH)2vitamin D3: genomic
      and non-genomic mechanisms.
AB  - The conformationally flexible secosteroid, 1alpha,25(OH)2vitamin D3
      (1alpha,25(OH)2D3) initiates biological responses via binding to the vitamin D
      receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic
      pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl
      like ligand configuration (gene transcription) or a planar-like ligand shape
      (rapid responses). When occupied by 1alpha,25(OH)2D3, the VDR-GP interacts with
      the retinoid X receptor to form a heterodimer that binds to vitamin D responsive
      elements in the region of genes directly controlled by 1alpha,25(OH)2D3. By
      recruiting complexes of either coactivators or corepressors, activated VDR
      modulates the transcription of genes encoding proteins that promulgate the
      traditional genomic functions of vitamin D, including signaling intestinal
      calcium and phosphate absorption to effect skeletal and calcium homeostasis.
      1alpha,25(OH)2D3/VDR control of gene expression and rapid responses also delays
      chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes,
      arteriosclerosis, vascular disease, and infection.

PMID- 21872796
TI  - Regulation of vitamin D metabolism.
AB  - Fundamental to understanding the way in which perturbations in the vitamin D
      endocrine system can affect human health is an appreciation of the steps involved
      in the production of the well-recognized active hormonal form, 1,25
      dihydroxyvitamin D(3). Thus this paper focuses first on the nature and regulation
      of the two enzymes responsible for the production of 1,25-dihydroxyvitamin D(3),
      the 25-hydroxylase in the liver and the 1alpha-hydroxylase in the kidney. The
      most important regulators of the 1alpha-hydroxylase in the kidney are 1,25
      dihydroxyvitamin D(3) itself, parathyroid hormone and FGF23. The extent and
      importance of extra-renal, 1,25-dihydroxyvitamin D(3) synthesis is then
      considered. Finally the features of the 24R-hydroxylase, which produces 24R,25
      dihydroxyvitamin D(3) in the kidney and is induced by and inactivated, 1,25
      dihydroxyvitamin D(3)in target cells are described.

PMID- 21872798
TI  - Calcemic actions of vitamin D: effects on the intestine, kidney and bone.
AB  - The analysis of mice that lack systemically the actions of the active form of
      vitamin D, 1,25(OH)2D, has shown that 1,25(OH)2D is an essential regulator of
      calcium homeostasis and that its actions are aimed at maintaining serum calcium
      levels within narrow limits. Especially the stimulation of intestinal calcium
      transport by 1,25(OH)2D is important for calcium and bone homeostasis. The
      involved transporters are however still elusive. The targeted deletion of
      1,25(OH)2D action in chondrocytes has provided compelling evidence for a
      paracrine control of bone development and endocrine regulation of phosphate
      homeostasis by 1,25(OH)2D. Targeting vitamin D receptor (VDR) function in other
      tissues will further enhance our understanding of the cell-type specific action
      of 1,25(OH)2D. In this review, we will discuss the current understanding and
      remaining questions concerning the calcemic actions of 1,25(OH)2D in the
      intestine, kidney and bone, with special focus on the evidence obtained by the
      use of transgenic mouse models.

PMID- 21872799
TI  - The role of vitamin D in paediatric bone health.
AB  - Recently there has been renewed interest in the role of vitamin D in paediatric
      bone health. Its role in the development of rickets and hypocalcaemia in infants
      and young children, in particular, in many part of the world is well known, and
      the importance of the prevention of vitamin D deficiency during pregnancy and
      lactation has been highlighted. Less clear are the possible effects that
      maintaining maternal vitamin D sufficiency might have on foetal and early infant
      growth and bone development. There is little evidence to suggest that maintaining
      childhood vitamin D status well above that necessary to prevent rickets has an
      effect on intestinal calcium absorption or on peak bone mass. Further studies are
      needed in these areas prior to definitive conclusions are drawn about the optimal
      vitamin D requirements and circulating 25(OH)D concentrations for foetal, infant
      and childhood bone health.

PMID- 21872800
TI  - The effect of vitamin D on bone and osteoporosis.
AB  - The main effect of the active vitamin D metabolite 1,25(OH)2D is to stimulate the
      absorption of calcium from the gut. The consequences of vitamin D deficiency are
      secondary hyperparathyroidism and bone loss, leading to osteoporosis and
      fractures, mineralization defects, which may lead to osteomalacia in the long
      term, and muscle weakness, causing falls and fractures. Vitamin D status is
      related to bone mineral density and bone turnover. Vitamin D supplementation may
      decrease bone turnover and increase bone mineral density. Several randomized
      placebo-controlled trials with vitamin D and calcium showed a significant
      decrease in fracture incidence. However, very high doses of vitamin D once per
      year may have adverse effects. When patients with osteoporosis are treated with a
      bisphosphonate, they should receive a vitamin D and calcium supplement unless the
      patient is vitamin D replete. These subjects are discussed in detail in this
      review. Finally, the knowledge gaps and research agenda are discussed.

PMID- 21872801
TI  - The anti-cancer and anti-inflammatory actions of 1,25(OH)2D3.
AB  - Various epidemiological studies have shown an aetiological link between vitamin D
      deficiency and cancer incidence. The active metabolite of vitamin D, 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3], has potent anti-cancer activities both in
      vitro and in vivo. These anti-cancer effects are attained by regulating the
      transcription of numerous genes that are involved in different pathways to reduce
      tumorigenesis and are dependent on the cancer cell type. Besides reducing cell
      growth and inducing apoptosis, 1,25(OH)2D3 also inhibits angiogenesis and
      metastasis. Moreover, its potency to inhibit inflammation also contributes to its
      anti-tumoral activity. Here, we report the different ways in which 1,25(OH)2D3
      interferes with the malignant processes that are activated in cancer cells.

PMID- 21872802
TI  - Vitamin D and cancer: clinical aspects.
AB  - There are substantial preclinical and epidemiologic data that suggest that
      vitamin D plays a role in the prevention and treatment of cancer. Numerous
      observational studies have shown that low blood levels of 25(OH) vitamin D
      (cholecalciferol), estimated by geographical location, diet and activity
      assessment or measured serum levels are associated with a higher risk of cancer
      and worse cancer-specific survival as well as numerous morbidities to e.g.
      cardiovascular disease, stroke, infection, autoimmune disease, and neuromuscular
      dysfunction among large populations. A considerable number of in vitro and in
      vivo studies indicate that the most active metabolite of vitamin D--1,25
      dihydroxycholecalciferol or calcitriol--has anti-proliferative, pro-apoptotic,
      pro-differentiating, and anti-angiogenic properties. Combined treatment of
      calcitriol and many types of cytotoxic agents has synergistic or at least
      additive effects. However, clinical trials testing these hypotheses have been
      less encouraging, though a number of methodological, pharmacological, and
      pharmaceutical issues confound all trials ever conducted. In order to properly
      assess the clinical value of vitamin D, its metabolites and analogs in cancer
      prevention and treatment, more studies are needed.

PMID- 21872803
TI  - Vitamin D in autoimmune, infectious and allergic diseases: a vital player?
AB  - Vitamin D is a steroid hormone that is acquired via diet or synthesized in the
      skin upon UV exposure and needs subsequent hydroxylation steps to become
      activated as 1,25-dihydroxyvitamin D. While widely known for its role in
      maintaining bone health, vitamin D receptors have also been identified in
      different immune cell types. Many immune cells can also convert vitamin D into
      its bioactive form, thus enhancing the locally available concentrations to those
      required for the immunomodulatory effects of vitamin D. In this review, we
      summarize the genetic and epidemiologic data potentially linking vitamin D to
      autoimmune, infectious and allergic diseases. We also discuss how vitamin D
      influences the immune responses in each of those conditions based on the data
      generated using patient samples or preclinical models of each of these diseases.

PMID- 21872804
TI  - Vitamin D: epidemiology of cardiovascular risks and events.
AB  - Vitamin D may influence blood pressure through the renin-angiotensin system,
      parathyroid hormone levels, myocardial function, inflammation, and vascular
      calcification. In the past several years, a number of high-quality prospective
      studies have examined 25(OH)vitamin D (25(OH)D) levels in relation to risk of
      cardiovascular disease (CVD). Studies consistently show that levels of 25(OH)D
      below 20-25 ng/mL are associated with an increased risk of CVD incidence or
      mortality. Risk appears especially elevated at 25(OH)D levels below 10 or 15
      ng/mL. It is unclear if levels higher that 25 ng/mL provide further benefits for
      CVD disease. Currently, results from randomized clinical trials are sparse and do
      not allow a definitive conclusion. Given other potential benefits of vitamin D,
      and low potential for toxicity, deficient levels below 25-30 ng/mL should be
      avoided and treated when identified. Further observational and randomized
      clinical trial data are important to better characterize the optimal range for
      25(OH)D.

PMID- 21872805
TI  - Vitamin D in chronic kidney disease.
AB  - In chronic kidney disease (CKD), abnormalities in vitamin D metabolism contribute
      to the development of mineral and skeletal disorders, elevations in parathyroid
      hormone (PTH), hypertension, systemic inflammation, renal and cardiovascular
      damage. CKD induces a progressive loss of the capacity of the kidney not only to
      convert 25-hydroxyvitamin D [25(OH)D] to circulating calcitriol, the vitamin D
      hormone, but also to maintain serum 25(OH)D levels for non-renal calcitriol
      synthesis. The resulting calcitriol and 25(OH)D deficiency associates directly
      with accelerated disease progression and death. This chapter presents our
      understanding of the pathophysiology behind 25(OH)D and calcitriol deficiency in
      CKD, of the adequacy of current recommendations for vitamin D supplementation and
      PTH suppression, and of potential markers of renal and cardiovascular lesions
      unrelated to PTH suppression, a knowledge required for the design of trials to
      obtain evidence-based recommendations for vitamin D and calcitriol replacement
      that improve outcomes at all stages of CKD.

PMID- 21872806
TI  - Vitamin D and the brain.
AB  - Vitamin D is a member of the superfamily of nuclear steroid transcription
      regulators and as such, exerts transcriptional control over a large number of
      genes. Several other steroids, such as thyroid hormones, vitamin A, androgens and
      the glucocorticoids, are known as 'neurosteroids' and their role in brain
      development and function is well defined. It has only been in the last decade or
      so that vitamin D has been thought to function as a neurosteroid. In this review
      we have collated a diverse array of data describing the presence of vitamin D
      metabolites and the receptor in the brain, the evidence that vitamin D may be an
      important modulator of brain development, and the potential role of vitamin D in
      neurological and neuropsychiatric disorders.

PMID- 21872807
TI  - Worldwide vitamin D status.
AB  - The aim of the present study is to summarize existing literature on vitamin D
      levels in adults in different continents and different countries worldwide. The
      best determinant of vitamin D status is the serum concentration of 25
      hydroxyvitamin D (25(OH)D). Most investigators agree that serum 25(OH)D should be
      higher than 50 nmol/l, but some recommend higher serum levels. Traditional risk
      groups for vitamin D deficiency include pregnant women, children, older persons,
      the institutionalized, and non-western immigrants. This chapter shows that serum
      25(OH)D levels are not only suboptimal in specific risk groups, but also in
      adults in many countries. Especially, in the Middle-East and Asia, vitamin D
      deficiency in adults is highly prevalent.

PMID- 21872808
TI  - Why the minimum desirable serum 25-hydroxyvitamin D level should be 75 nmol/L (30
      ng/ml).
AB  - The Institutes of Medicine (IOM) recently revised the recommended dietary
      allowances (RDA) for vitamin D, to maintain serum 25-hydroxyvitamin D (25(OH)D)
      at or above 50 nmol/L, to sustain bone density, calcium absorption, and to
      minimize risk of osteomalacia and rickets. However there are compelling reasons
      why 25(OH)D should preferably exceed 75 nmol/L: (A) Scrutiny of actual data
      specified by the IOM relating 25(OH)D to bone density and osteomalacia shows the
      desirable minimum 25(OH)D to be 75 nmol/L (30 ng/mL). (B) Humans are primates,
      optimized through evolution to inhabit tropical latitudes, with serum 25(OH)D
      over 100 nmol/L. (C) Epidemiologic relationships show health benefits if 25(OH)D
      levels exceed 70 nmol/L; these include fewer falls, better tooth attachment, less
      colorectal cancer, improved depression and wellbeing. Some studies of populations
      at high-latitude relate higher 25(OH)D to risk of prostate cancer, pancreatic
      cancer or mortality. Those relationships are attributable to the dynamic
      fluctuations in 25(OH)D specific to high latitudes, and which can be corrected by
      maintaining 25(OH)D at steady, high levels throughout the year, the way they are
      in the tropics. (D) There are now many clinical trials that show benefits and/or
      no adversity with doses of vitamin D that raise serum 25(OH)D to levels beyond 75
      nmol/L. Together, the evidence makes it very unlikely that further research will
      change the conclusion that risk of disease with serum 25(OH)D higher than 75
      nmol/L is lower than the risk of disease if the serum 25(OH)D is approximately 53
      nmol/L.

PMID- 21872809
TI  - Why modest but widespread improvement of the vitamin D status is the best
      strategy?
AB  - Vitamin D is a precursor for a secosteroid ligand of a major transcription
      factor, VDR, and is vital for normal bone mineralization. It also regulates many
      other genes so that it may be involved in many extra skeletal health effects. The
      optimal vitamin D status is controversial but there is a wide unanimity that the
      vitamin D status can and should be improved for some risk groups. To normalize
      serum calcium homeostasis as based on normal levels of serum 1,25(OH)2D3 or
      parathyroid hormone, or to optimize intestinal calcium absorption or bone mineral
      density in adults or elderly subjects, serum 25OHD should be 20 ng/ml or higher.
      A daily vitamin D supplement of at least 400 IU or preferably 800 IU of vitamin
      D3 can reduce the risk of fractures and probably also falls in elderly subjects,
      especially when combined with an optimal calcium intake. There is no formal proof
      of causality to define an optimal vitamin D intake or serum 25OHD based on its
      presumed extra skeletal health effects but the guidelines for bone health would
      probably eliminate also most negative extra skeletal health effects. The
      recommended vitamin D3 supplement of 400-800 IU/d for adults also corresponds to
      the daily replacement dose calculated from metabolic clearance studies.

PMID- 21872810
TI  - Is recurrent vaginal melanoma a lethal disease?

PMID- 21872811
TI  - Chart review: a blessing or a curse?

PMID- 21872812
TI  - Intra-articularly applied pulsed radiofrequency can reduce chronic knee pain in
      patients with osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is the most widespread chronic joint disease
      worldwide. Symptomatic knee OA is observed in approximately 12% of individuals
      more than 60 years of age. Conservative treatments models may not be effective
      always, and that some of them have serious adverse effects that prompted the
      researchers to research different treatment methods. In this study, we
      investigated short- and mid-term effectiveness of intra-articular pulsed
      radiofrequency (PRF) applied in patients with chronic knee pain due to OA.
      METHODS: This study was carried out in the pain management center of a university
      hospital between January 2009 and June 2009. The patient record files of 31
      patients who received intra-articular PRF were retrospectively reviewed. The
      antero-lateral area of the knee, where the intervention would be applied, was
      anesthetized with 1% lidocaine. An introducer needle was placed intra
      articularly. PRF was started as 42 degrees C at 2 Hz for 15 minutes. The pain of
      the patients was evaluated by 10 cm Visual Analog Scale (VAS). Furthermore, the
      ages, the gender, the symptom duration of the patients, the side of the knee on
      which the intervention was applied, and the complications were collected for
      statistical evaluation. RESULTS: Although the mean initial VAS scores of the
      patients were 6.1 +/- 0.9 cm, it was found, respectively, to be 3.9 +/- 1.9 cm
      and 4.1 +/- 1.9 cm at the first- and sixth-month follow-ups. In general, a
      decrease of 32.8% in mean in the VAS scores was achieved in the last follow-up;
      whereas the rate of patients reporting a minimum decrease of 2 points in the VAS
      scores was 64.5% and the rate of patients reporting a decrease of >=50% in their
      pain was calculated as 35.5%. CONCLUSION: PRF applied to the knee joint appears
      to be an effective and safe method.

PMID- 21872813
TI  - Spleen artery embolization increases the success of nonoperative management
      following blunt splenic injury.
AB  - BACKGROUND: Spleen artery embolization (SAE) may increase the success rate of
      nonoperative management (NOM). The present study investigated the clinical
      outcome after the installation of SAE in the management of blunt splenic injury.
      METHODS: A retrospective review of hospital records was performed to enroll
      patients with blunt injury of the spleen. Demographic data and information about
      the injury severity score, organ injury scale, hospitalization days, management
      and final outcomes were evaluated. Patients were separated into early and late
      groups according to the year that SAE was selectively used (2003-2004 and 2005
      2008). RESULTS: Six of eleven (55%) patients in the early group were successfully
      managed without surgery for blunt splenic injury, whereas all of the 38 patients
      (100%) in the late group were successfully managed without surgery. Eleven
      patients (11 of 38; 28.9%) received SAE in the late group. The rate of NOM
      increased from 55% in the early group to 100% in the late group (p < 0.001). Both
      early and late groups had similar injury severity score, length of
      hospitalization, blood transfusion, and complications, and there was no
      mortality. CONCLUSION: Performance of SAE for the patients with blunt splenic
      injury could increase the successful rate of NOM significantly and safely. An
      algorithm including the angioembolization might be beneficial in the management
      of patients with blunt spleen trauma.

PMID- 21872814
TI  - Patients and surgery-related factors that affect time to recovery of
      consciousness in adult patients undergoing elective cardiac surgery.
AB  - BACKGROUND: Central nervous system dysfunction is a serious complication
      following cardiac surgery. The prompt and predictable recovery of consciousness
      (ROC) from anesthesia is essential for neurological evaluations. This
      retrospective study aimed to determine the factors that were related to ROC time
      after elective cardiac surgery. METHODS: Patients receiving elective cardiac
      surgery under general anesthesia were included in the analysis. Patient and
      surgery-related factors were collected through chart review. Cox regression model
      was used to evaluate the associations between collected variables and ROC time.
      Backward model selection strategy was further applied to selecting independent
      factors from significant ones that affected ROC time in the univariate analysis.
      RESULTS: A total of 253 patients were recruited in our study. Among significant
      patient characteristics, higher body mass index (hazard ratio, HR = 1.06) and
      female gender (HR = 1.72) tended to shorten ROC time, but older age was inclined
      to prolong it (HR = 0.98). Higher preoperative blood urea nitrogen level also
      significantly delayed ROC after cardiac surgery (HR = 0.99). Among surgery
      related factors, only longer duration of cardiopulmonary bypass significantly
      increased ROC time after the model selection processes (HR = 0.96). Other factors
      were not significant after adjustment for these five factors. CONCLUSION: This
      study demonstrated that older age, male gender, lower body mass index, higher
      preoperative blood urea nitrogen level, and longer bypass duration were
      independent risk factors of delayed emergence after elective cardiac surgery.
      These findings provide insights into patient care and anesthetic management for
      clinicians in related fields.

PMID- 21872815
TI  - A single small dose of ketamine prevents lung injury following hepatic ischemia
      reperfusion in rabbits.
AB  - BACKGROUND: Previous studies demonstrated that large-dose ketamine alleviated
      lipopolysaccharide-induced lung injury. We investigated whether a single small
      dose of ketamine could attenuate lung injury induced by hepatic ischemia
      reperfusion (HIR) and, if so its underlying mechanisms. METHODS: Thirty male New
      Zealand rabbits were randomized into three groups (n = 10 each): sham group
      (Group S), control group (Group C), and ketamine group (Group K). In Group S,
      hepatic portal vein (HPV) and inferior vena cava (IVC) were left unclamped and
      0.9% saline 1 mL/kg was given intravenously. In Group K, ketamine 0.5 mg/kg (0.5
      mg/mL) was given intravenously 10 minutes before cross-clamping of the HPV and
      the IVC. In Group C, 0.9% saline was given 10 minutes before the cross-clamping.
      The HPV and the IVC were cross-clamped with bulldog clamps and unclamped 60
      minutes later in the Group K and the Group C. Blood pressure and pulse rate were
      recorded throughout the procedure. Rabbits were sacrificed 6 hours
      postoperatively. Lung W/D ratio was calculated and expression of tumor necrosis
      factor-alpha mRNA, intracellular adhesion molecule-1 mRNA, and nuclear factor
      kappa B (NF-kappaB)/p65 were quantitatively analyzed. Accumulation of neutrophils
      in lung tissues was also observed. RESULTS: Small dose of ketamine alleviated the
      pulmonary edema, but not the systemic hypotension, induced by cross-clamping of
      the IVC and the HPV. Pretreatment with ketamine significantly reduced the
      increments of tumor necrosis factor-alpha mRNA, intracellular adhesion molecule-1
      mRNA, and NF-kappaB/p65; and inhibited the aggregation of neutrophils in lung
      tissues following HIR. CONCLUSION: 0.5 mg/kg ketamine pretreatment showed
      significant protective effect on acute lung injury induced by HIR, which might be
      mediated by the NF-kappaB pathway.

PMID- 21872816
TI  - Risk of post-vertebroplasty fracture in adjacent vertebral bodies appears
      correlated with the morphologic extent of bone cement.
AB  - BACKGROUND: New fractures in adjacent vertebral bodies were found after
      percutaneous vertebroplasty. We evaluated the correlation between extent of
      polymethylmethacrylate cement and occurrence of post-vertebroplasty fractures in
      patients with osteoporosis. METHODS: Totally 162 adjacent vertebral bodies with
      no fracture at the time of vertebroplasty and the distribution of cement in
      corresponding treated vertebral bodies of 98 patients were included for the
      evaluation. Length of follow-up after vertebroplasty was 734 +/- 314 days (range,
      366-1838 days). Based on proximity of bone cement to the adjacent vertebral body,
      cement extent was classified as disc level (the closest), endplate level, or
      trabecula level (the farthest). RESULTS: Forty-one adjacent vertebrae had post
      vertebroplasty fracture occurring 2-1038 days after vertebroplasty. The
      percentages of adjacent vertebral bodies having post-vertebroplasty fracture
      about cement extent were: disc level, 44; endplate level, 29; and trabecula
      level, 7. CONCLUSION: Our study revealed that the risk of subsequent fracture in
      the adjacent vertebral bodies was correlated with the extent of bone cement after
      vertebroplasty. Preventive measures can be taken from this observation to reduce
      the percentage of post-vertebroplasty fracture in adjacent vertebral bodies.

PMID- 21872818
TI  - Nosocomial nasal myiasis in an intubated patient.
AB  - We report a case of nasal myiasis caused by Sarcophaga spp., noted during
      hospitalization. A 74-year-old man was admitted with non-ST-elevation myocardial
      infarction. The patient underwent coronary arterial bypass surgery and was then
      mechanically ventilated by means of a nasotracheal tube for the next 8 days.
      After extubation, a total of seven maggots were retrieved from both nostrils. The
      larvae were removed and reared to mature flies, which were identified as
      Sarcophaga peregrina. From the clinical course and the fly's life cycle, it was
      concluded that the infestation was hospital-acquired.

PMID- 21872817
TI  - A rapid screening test for depression in junior high school children.
AB  - BACKGROUND: Depression generates a remarkable disease burden. Early onset of
      depression in young people is associated with a poor prognosis. This has
      precipitated developing a screening instrument for early detection of depression
      in Taiwan adolescents. METHODS: We recruited 662 junior high school students who
      completed the Screening Test for Depression (STD) designed using diagnostic and
      statistical manual-IV diagnostic criteria of major depressive disorder for
      assessing depressive symptoms. The students were then interviewed by
      psychiatrists who used the Mini International Neuropsychiatric Interview-Kid to
      verify the validity of the soon-to-be-developed Rapid STD (RSTD). Multiple
      logistic regression analysis of the STD results was used to extract items for the
      RSTD. RESULTS: We extracted four items for the RSTD: "insomnia or hypersomnia",
      "recurrent thoughts of death or recurrent suicidal ideation", "feelings of
      worthlessness or excessive or inappropriate guilt", and "psychomotor agitation or
      retardation". Any two of the first three yielded the best-balanced algorithm for
      major depressive disorder, which had a sensitivity of 75.0%, specificity of
      92.9%, positive predictive value of 28.6%, and negative predictive value of
      99.0%. Any two of the four yielded the best-balanced algorithm for depressive
      disorders, which had a sensitivity of 71.4%, specificity of 92.0%, the positive
      predictive value of 33.3%, and the negative predictive value of 98.3%.
      CONCLUSION: The RSTD, a 4-item tool for junior high school children, can be
      easily used to assess fluctuating risks of major depressive disorder and
      depressive disorders at any time.

PMID- 21872819
TI  - Giant branching aneurysmal aberrant systemic artery for intralobar pulmonary
      sequestration: computed tomographic depiction of arterial and bronchial anomaly.
AB  - Aberrant systemic arteries supplying the intralobar pulmonary sequestration can
      become dilated and have atherosclerotic change. Computed tomography is very
      useful in demonstrating the aberrant artery. We report a case of intralobar
      pulmonary sequestration with giant branching aneurysmal aberrant artery, and
      demonstrated the discontinuity of the bronchus by 64-slice computed tomography,
      which has not previously been described.

PMID- 21872820
TI  - Primary malignant melanoma of the vagina with repeated local recurrences and
      brain metastasis.
AB  - Malignant melanoma of the vagina, a very rare malignancy, has a notoriously
      aggressive behavior associated with a high risk of local recurrence and distant
      metastasis. At present, there are various treatment options for this disease but
      no standard guideline. We describe a case of a 54-year-old woman with a locally
      advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy
      with interferon-alpha-2b, chemotherapy, radiotherapy, and repeat excision of
      local recurrent lesions and brain metastasis. In conclusion, malignant melanoma
      of the vagina has a high risk for local recurrence. Repeated local excision
      followed by biochemotherapy is a tolerable treatment.

PMID- 21872821
TI  - A reflection on Fukushima nuclear disaster: view of Taiwan doctor.

PMID- 21872823
TI  - Interphase fluorescence in situ hybridization analysis detects a much higher rate
      of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic
      subgroups than conventional cytogenetics.
AB  - In benign thyroid lesions, three main cytogenetic subgroups, characterized by
      trisomy 7 or structural aberrations involving either chromosomal region 19q13.4
      or 2p21, can be distinguished by conventional cytogenetics (CC). As a rule, these
      aberrations seem to be mutually exclusive. Interphase fluorescence in situ
      hybridization (I-FISH) analysis on benign as well as malignant thyroid neoplasias
      has been performed in the past, but rarely in combination with CC. In the present
      paper, we have analyzed 161 benign thyroid lesions both with CC and I-FISH on
      touch preparations by using a multi-target, triple-color FISH assay as well as
      dual-color break-apart probes for detection of the main cytogenetic subgroups.
      Within the samples, I-FISH detected tumors belonging to either of the subgroups
      more frequently than CC (23 vs. 11.4%), either due to small subpopulations of
      aberrant cells or to cryptic chromosomal rearrangements (three cases). Thus, I
      FISH seems to be more sensitive than CC, particularly in the detection of
      subpopulations of cells harboring cytogenetic aberrations that may be overlooked
      by CC. In summary, I-FISH on touch preparations of benign thyroid lesions seems
      to be a favorable method for cytogenetic subtyping of thyroid lesions.

PMID- 21872822
TI  - Promiscuous partnerships in Ewing's sarcoma.
AB  - Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and
      young adults. At the molecular genetic level Ewing's sarcoma is characterized by
      a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an
      oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific
      chimeric fusion retains the amino terminus of EWS, a member of the TET
      (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI,
      a member of the ETS family of transcription factors. In addition to EWS/FLI,
      variant translocation fusions belonging to the TET/ETS family have been
      identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS
      fusions in the pathogenesis of Ewing's sarcoma and have since been used as
      diagnostic markers for the disease. EWS fusions with non-ETS transcription factor
      family members have been described in sarcomas that are clearly distinct from
      Ewing's sarcoma. However, in recent years there have been reports of rare fusions
      in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the
      carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS
      proteins. This review aims to summarize the growing list of fusion oncogenes that
      characterize Ewing's sarcoma and Ewing's-like tumors and highlights important
      questions that need to be answered to further support the existing concept that
      Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding
      the molecular mechanisms of action of the various different fusion oncogenes will
      provide better insights into the biology underlying this rare but important solid
      tumor.

PMID- 21872824
TI  - Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive
      germline and somatic study.
AB  - PPP2R2A, mapped to 8p21.2, codes for the alpha isoform of the regulatory B55
      subfamily of protein phosphatase 2 (PP2A). PP2A is one of the four major
      serine/threonine phosphatases and is implicated in the negative control of cell
      growth and division. Because of its known functions and location within a
      chromosomal region where evidence for linkage and somatic loss of heterozygosity
      was found, we hypothesized that either somatic copy number changes or germline
      sequence variants in PPP2R2A may increase prostate cancer (PCa) risk. We examined
      PPP2R2A deletion status in 141 PCa samples using Affymetrix SNP arrays. It was
      found that PPP2R2A was commonly (67.1%) deleted in tumor samples, including a
      homozygous deletion in three tumors (2.1%). We performed a mutation screen for
      PPP2R2A in 96 probands of hereditary prostate cancer families. No high risk
      mutations were identified. In addition, we re-analyzed 10 SNPs of PPP2R2A in
      sporadic PCa cases and controls. No significant differences in the allele and
      genotype frequencies were observed among either PCa cases and controls or PCa
      aggressive and non-aggressive cases. Taken together, these results suggest that a
      somatic deletion rather than germline sequence variants of PPP2R2A may play a
      more important role in PCa susceptibility.

PMID- 21872825
TI  - Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines.
AB  - Phenobarbital (PB), a nongenotoxic carcinogen, activates the nuclear constitutive
      active/androstane receptor (CAR), resulting in the transcriptional induction or
      repression of various hepatic genes. We previously demonstrated that liver tumors
      developed after chronic PB treatment only when CAR is present. To understand the
      molecular mechanism of tumor promotion, cDNA microarray analysis was performed.
      We identified tubulin alpha 8 (TUBA8) as one of the candidate genes that may be
      involved in liver tumor promotion. Tuba8 mRNA was induced with PB treatment in
      mouse livers before tumor development as well as in tumor tissues. Because the
      functions of TUBA8 are unknown in liver, we investigated the effects of TUBA8
      gene expression on cell growth, proliferation, and cell migration. Sense or
      antisense cDNA for Tuba8 was stably transfected into Huh7 and HepG2 cells.
      Exogenous overexpression of Tuba8 inhibited cell growth and proliferation in Huh7
      but not in HepG2 cells, while cell migration was increased in HepG2 cells but not
      Huh7 cells. These results indicate that TUBA8 can play a role in the regulation
      of cell growth, proliferation, and cell migration in a cell-specific manner in
      vitro, suggesting that TUBA8 may contribute to mouse liver tumorigenesis through
      these functions.

PMID- 21872826
TI  - Frequent EVI1 translocations in myeloid blast crisis CML that evolves through
      tyrosine kinase inhibitors.
AB  - Clinical variables associated with ecotropic viral integration site 1 (EVI1)
      translocations were evaluated in 42 consecutive chronic myeloid leukemia (CML)
      patients in myeloid blast crisis (MBC). Translocations were confirmed with
      fluorescence in situ hybridization, and Western blot analysis demonstrated EVI1
      expression. Translocations of EVI1 were present in 3 of 24 (12%) patients whose
      disease evolved MBC before tyrosine kinase inhibitor (TKI) exposure, and 7 of 18
      (39%) patients who had received one or more TKIs. Univariate analysis showed that
      prior TKI therapy was the only clinical variable that was significantly
      associated with EVI1 translocation (P = 0.047). TKI-resistant BCR-ABL1 mutations
      were present in 71% of MBC patients with EVI1 translocations at the time of
      disease progression. These observations suggest that EVI1 overexpression
      collaborates with BCR-ABL1 in the evolution of TKI-resistant MBC. Inhibition of c
      ABL kinase-mediated DNA double-strand repair by TKIs may predispose to EVI1
      translocation in this setting.

PMID- 21872827
TI  - Tumor suppressor gene ZAC/PLAGL1: altered expression and loss of the nonimprinted
      allele in pheochromocytomas.
AB  - ZAC/PLAGL1 is a novel imprinted tumor suppressor gene encoding an important
      inducer of cell cycle arrest and apoptosis, and found to be lost during
      tumorigenesis. We analyzed the significance of ZAC in the development of a rare,
      usually benign tumor of the adrenal gland: pheochromocytoma (PCC). Twenty-four
      PCCs were analyzed for the loss of the active nonimprinted allele of ZAC, and
      nine of the twenty-four PCCs were also assayed for expression of the protein. In
      thirteen of the cases, a paired nonmalignant tissue was available for analysis.
      Methylation-specific polymerase chain reaction revealed frequent (15 of 23, 65%)
      loss of unmethylated DNA in the imprinting control region of ZAC.
      Immunohistochemistry identified reduced ZAC expression in 56% (5 of 9) of the
      subset cases. Four of the five PCC cases where reduced expression of ZAC was
      observed were also positive for the loss of the active ZAC allele. Additionally,
      the loss of ZAC expression was also found to be frequent in a series of capillary
      hemangioblastomas and gliomas (6 of 6, 100%, and 17 of 27, 63%, respectively)
      examined for comparison. In conclusion, our study suggests the involvement of the
      imprinted ZAC gene in the pathogenesis of PCC.

PMID- 21872829
TI  - Cytogenetic and molecular characteristics of 25 Chilean patients with a variant
      Ph translocation.
AB  - Chronic myeloid leukemia (CML) is characterized by the presence of the
      Philadelphia chromosome (Ph), which results from a balanced translocation between
      chromosomes 9 and 22, the t(9;22)(q34;q11.2). In 5-10% of the cases, variants of
      the Ph (vPh) are detected, involving various breakpoints in addition to 9q34 and
      22q11.2. Deletions on the der(9) and der(22) can be detected in approximately 10
      15% of CML patients. The frequency of a deletion of the der(9) in vPh CML is
      variable. Most studies have shown high frequencies (30-45%) in this subgroup. We
      report the cytogenetic evaluation of 25 vPh cases, which represents 6.8% of the
      CML cases diagnosed at one institution in 20 years. The breakpoints of the
      partners of the vPh in our patients agree with those reported previously, except
      for a novel 18q23. We found a low incidence of deletions of the der(9) (10%) and
      der(22) (5%) in these patients, contrasting with several reports in the
      literature. This finding may reflect the extensive spectrum of aberrations in
      vPh, and the possibility that a considerable group of these aberrations may not
      affect the genetic stability of 5'ABL1 and 3'BCR. Epidemiologic differences may
      also exist and could explain our results. These differences would require further
      investigation.

PMID- 21872828
TI  - Absence of TCR loci chromosomal translocations in cutaneous T-cell lymphomas.
AB  - Chromosomal aberrations involving T-cell receptor (TCR) gene loci have been
      described in several T-cell malignancies. In primary cutaneous T-cell lymphomas
      (CTCL), the frequency of these aberrations has not yet been well established. We
      analyzed TCR gene loci (TCRAD, TCRB, and TCRG) status in CTCLs by fluorescence in
      situ hybridization (FISH). Twenty-five patients with CTCLs were included in the
      study: 13 Sezary syndromes (SS), six tumoral stage mycosis fungoides (MFt), and
      six primary cutaneous anaplastic large cell lymphomas CD30(+) (cALCL-CD30(+)).
      FISH was performed with three break-apart probes flanking TCRAD (14q11), TCRB
      (7q34), and TCRG (7p14) loci in each case. TCR gene chromosomal rearrangements
      were not detected in any of the analyzed cases. Gains of TCRB and TCRG genes were
      observed in 23% (3 of 13) of SS and 50% (3 of 6) of MFt, reflecting the presence
      of trisomy and/or tetrasomy of chromosome 7 already detected by conventional
      cytogenetics and array comparative genetic hybridization techniques. TCR loci
      rearrangements are not frequent in CTCLs; however, we cannot exclude a pathogenic
      role in these malignancies.

PMID- 21872830
TI  - [Botulinum toxin A for the treatment of familial benign pemphigus].
AB  - Familial benign pemphigus or Hailey-Hailey disease is a rare bullous disease that
      presents clinically with recurrent flares of erosions and vesicles that mainly
      affect the skinfolds. Many topical and systemic therapies have been proposed.
      Hyperhidrosis is one of the factors that can trigger or aggravate a flare-up, and
      its treatment is therefore important for controlling the disease and preventing
      further episodes. We report 3 patients with axillary and/or inguinal benign
      familial pemphigus that responded favorably to treatment with subcutaneous
      botulinum toxin.

PMID- 21872831
TI  - [Recurrent pyogenic granuloma].
AB  - The appearance of multiple satellite lesions is a rare complication of the
      treatment of a primary pyogenic granuloma lesion. We report 5 cases of recurrent
      pyogenic granuloma in patients aged between 4 and 31 years. The lesions resolved
      spontaneously after 1 to 9 months. Although the diagnosis and treatment of
      recurrent pyogenic granuloma can be problematic, this condition is benign and
      frequently self-limiting.

PMID- 21872832
TI  - [Sarcoid-type allergic contact granuloma caused by earrings in a boy].

PMID- 21872833
TI  - [Intense pulsed light therapy for lupus pernio].

PMID- 21872834
TI  - [Myxoid dermatofibrosarcoma protuberans in childhood].
AB  - Dermatofibrosarcoma protuberans is a locally aggressive skin tumor that affects
      young and middle-aged adults. A number of histological variants have been
      described, the myxoid type being one of the least common. Microscopically it is
      formed of a neoplastic growth that is located in the dermis and hypodermis and
      has a predominant myxoid component. Peripherally there are infiltrating bundles
      of spindle-shaped cells that are diffusely positive for the CD34
      immunohistochemical marker. We report a case of myxoid dermatofibrosarcoma
      protuberans on a finger of the left hand of a 14-year-old girl. The tumor had
      been present for at least 10 years. This is the first pediatric case of myxoid
      dermatofibrosarcoma protuberans at this site. This histological subtype has
      mainly been described on the extremities in adults and is very rare in children.
      We discuss the differential diagnosis with other CD34(+) myxoid mesenchymal
      tumors.

PMID- 21872835
TI  - [Use of 64-slice tomodensitometry after cardiac arrest].
AB  - Acute coronary occlusion is the leading cause of out-of-hospital cardiac arrest,
      so patients are usually referred for immediate coronary angiography and
      angioplasty. We report here the observation of such a patient who previously
      underwent a coronary artery bypass intervention and who had a difficult arterial
      access. Moreover, the nature of the grafts was unknown (saphenous and/or mammary
      arteries). Multi-slice cardiac tomo-densitometry was performed rather than a
      conventional coronary angiography and it allowed the analysis of native arteries
      and grafts. There was no stenosis and angioplasty was unnecessary.

PMID- 21872836
TI  - [Prevalence and factors related to therapeutic adherence among black African
      outpatients with stable coronary artery disease in a cardiology department of
      Dakar in Senegal].
AB  - INTRODUCTION: The management of coronary artery disease has made important
      progress. Adherence to therapeutic measures is a great challenge for improving
      the long-term prognosis. In this work, we evaluate factors related to therapeutic
      adherence in black African patients with stable coronary artery disease.
      METHODOLOGY: We conducted a survey over three months (February-May 2008) in three
      cardiology departments in Dakar. We studied the regularity of drug intake, the
      adherence to the dietary advices and the appointments for consultation as well as
      the factors related to adherence. Good adherence was defined by a compliance rate
      greater or equal to 80% and a compliance rate less than 40% defined poor
      adherence. RESULTS: We included 105 patients (61 men) with a mean age of 60.67+/
      11.29 years. Good compliance was noted in 56.2% of cases for drug treatment, 42%
      for dietary advices and 65% for appointments for consultation. A history of acute
      coronary events (P=0.04), a good knowledge of the disease (P=0.03) and a
      healthcare (P=0.02) were the factors related to a good adherence to drug
      treatment, whereas ischemic cardiomyopathy was a factor for poor adherence
      (P=0.002). Knowledge of coronary disease was the only factor correlated with good
      adherence to lifestyle (P=0.014). CONCLUSION: Therapeutic adherence remains
      unsatisfactory in Black African patients with stable coronary artery disease,
      hence the importance of patient education to reach a good adherence for
      therapeutic, because better adherence improves long-term prognosis of coronary
      artery disease.

PMID- 21872837
TI  - Acute kidney injury: a relevant complication after cardiac surgery.
AB  - Acute kidney injury (AKI) occurs in as many as 40% of patients after cardiac
      surgery and requires dialysis in 1% of cases. Acute kidney injury is associated
      with an increased risk of mortality and morbidity, predisposes patients to a
      longer hospitalization, requires additional treatments, and increases the
      hospital costs. Acute kidney injury is characterized by a progressive worsening
      course, being the consequence of an interplay of different pathophysiologic
      mechanisms, with patient-related factors and cardiopulmonary bypass as major
      causes. Recently, several novel biomarkers have emerged, showing reasonable
      sensitivity and specificity for AKI prediction and protection. The development
      and implementation of potentially protective therapies for AKI remains essential,
      especially for the relevant impact of AKI on early and late survival.

PMID- 21872838
TI  - Is there a relationship between fatigue questionnaires and gait mechanics in
      persons with multiple sclerosis?
AB  - OBJECTIVE: To evaluate reported fatigue levels and gait deficits in patients with
      multiple sclerosis (MS) to determine the relationships that may exist between
      fatigue in patients with MS and alterations in gait mechanics. DESIGN: Cross
      sectional. SETTING: Biomechanics laboratory. PARTICIPANTS: Subjects with MS
      (n=32) and age- and sex-matched controls (n=30). INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Fatigue Severity Scale (FSS), Modified Fatigue Index Scale
      (MFIS), and 36-Item Short Form Health Survey (SF-36) to assess fatigue and
      general health. Biomechanical gait analysis was performed to measure peak joint
      torques and powers in the sagittal plane at the ankle, knee, and hip.
      Correlations were performed between fatigue measures and degree of deficit within
      each patient with MS for each joint torque and power measure. RESULTS: FSS score
      significantly correlated with deficits in ankle power generation at late stance
      and walking velocity. MFIS score significantly correlated with deficits in peak
      knee extensor torque and knee power absorption at early stance. SF-36 subscale
      scores correlated with several joint torque and power variables. CONCLUSIONS:
      Subjective fatigue rating scale scores alone should not be used as an indicator
      of motor disability or disease progression as it affects walking performance of
      patients with MS.

PMID- 21872839
TI  - Health-related quality of life in patients with poststroke emotional
      incontinence.
AB  - OBJECTIVE: To assess the effect of poststroke emotional incontinence (PSEI) on
      health-related quality of life (HRQOL). DESIGN: Cross-sectional observational
      study. SETTING: Psychiatric clinic. PARTICIPANTS: Stroke survivors (N=385;
      consecutive series) discharged from the acute stroke unit between December 2004
      and June 2007. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Chinese
      (Hong Kong) version of the 36-Item Short Form Health Survey (SF-36) for HRQOL.
      RESULTS: Fifty-eight (15.1%) patients had PSEI. After adjustment for possible
      demographic and clinical confounders, subjects with PSEI had significantly lower
      physical and mental summary scores, particularly in the General and Mental
      Health, Social Function, and Role-Emotional subscales of the SF-36. CONCLUSION:
      PSEI has an independent effect on HRQOL. Longitudinal studies of stroke are
      warranted to confirm and extend this finding.

PMID- 21872840
TI  - Test-retest reliability of isometric and isokinetic knee extension and flexion in
      patients with fibromyalgia: evaluation of the smallest real difference.
AB  - OBJECTIVE: To investigate the reliability of isokinetic peak torque and work and
      isometric peak torque measurements for knee flexion and extension in fibromyalgia
      (FM) patients by determining the smallest real difference (SRD). DESIGN: Test
      retest reliability study. SETTING: University laboratory. PARTICIPANTS: Women
      with FM (N=37) aged between 34 and 74 years. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The participants performed isometric, concentric, and eccentric
      tests of the knee. Unilateral maximal peak torque and average work were measured
      for each direction (flexion, extension) and contraction (isometric, concentric,
      eccentric) type. Relative reliability, absolute reliability, and SRD were
      calculated. The 3 tests were repeated after an interval of 7 days. RESULTS: With
      the exception of eccentric flexion, all peak torque measures had an intraclass
      correlation coefficient (ICC) of > 0.90, and all work measures had an ICC of >
      0.85. The SRD ranged between 21% and 37% for all peak torque measures and between
      40% and 73% for all work measures. CONCLUSIONS: Isokinetic dynamometry provides
      reliable measurement of peak torque and work for isometric, concentric, and
      eccentric knee flexion and extension in patients with FM. The present study has
      generated novel SRD data, which will assist physicians, therapists, and
      clinicians in interpreting posttreatment changes in patients with FM.

PMID- 21872841
TI  - Assessing physical function in adult acquired major upper-limb amputees by
      combining the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome
      Questionnaire and clinical examination.
AB  - OBJECTIVES: To describe physical function in adult acquired major upper-limb
      amputees (ULAs) by combining self-assessed arm function and physical measures
      obtained by clinical examinations; to estimate associations between background
      factors and self-assessed arm function in ULAs; and to assess whether clinical
      examination findings may be used to detect reduced arm function in unilateral
      ULAs. DESIGN:  SURVEY: postal questionnaires and clinical examinations. SETTING:
      Norwegian ULA population. Clinical examinations performed at 3 clinics.
      PARTICIPANTS: Questionnaires: population-based sample (n=224; 57.4% response
      rate). Clinical examinations: combined referred sample and convenience sample of
      questionnaire responders (n=70; 83.3% of those invited). SURVEY inclusion
      criteria: adult acquired major upper-limb amputation, resident in Norway,
      mastering of spoken and written Norwegian. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The Disabilities of the Arm, Shoulder and Hand (DASH) Outcome
      Questionnaire, and clinical examination of joint motion and muscle strength with
      and without prostheses. RESULTS: Mean DASH score was 22.7 (95% confidence
      interval [CI], 20.3-25.0); in bilateral amputees, 35.7 (95% CI, 23.0-48.4); and
      in unilateral amputees, 22.1 (95% CI, 19.8-24.5). A lower unilateral DASH score
      (better function) was associated with paid employment (vs not in paid employment:
      adjusted regression coefficient [aB]=-5.40, P=.033; vs students: aB=-13.88,
      P=.022), increasing postamputation time (aB=-.27, P=.001), and Norwegian
      ethnicity (aB=-14.45, P<.001). At clinical examination, we found a high frequency
      of impaired neck mobility and varying frequencies of impaired joint motion and
      strength at the shoulder, elbow, and forearm level. Prosthesis wear was
      associated with impaired joint motion in all upper-limb joints (P<.006) and with
      reduced shoulder abduction strength (P=.002). Impaired without-prosthesis joint
      motion in shoulder flexion (ipsilateral: aB=12.19, P=.001) and shoulder abduction
      (ipsilateral: aB=12.01, P=.005; contralateral: aB=28.82, P=.004) was associated
      with increased DASH scores. CONCLUSIONS: Upper-limb loss clearly affects physical
      function. DASH score limitation profiles may be useful in individual clinical
      assessments. Targeted clinical examination may indicate patients with extra
      rehabilitational needs. Such examinations may be of special importance in
      relation to prosthesis function.

PMID- 21872842
TI  - Step performance in persons with rheumatoid arthritis: a case-control study.
AB  - OBJECTIVE: To investigate factors that could lead to falls in patients with
      rheumatoid arthritis (RA). DESIGN: Case-control study. SETTING: Hospital.
      PARTICIPANTS: Patients with RA (n=15) and age- and sex-matched controls (n=15;
      mean +/- SD age, 60.5 +/- 7.1y). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Performance of participants on a step task. Furthermore, manual
      performance was assessed, as well as questionnaires for balance confidence, fear
      of falling, and activity level. RESULTS: Patients with RA showed nonsignificantly
      increased RTs (time to anticipatory postural adjustment and foot lift) and
      significantly increased movement times (MTs). Push-off force and step velocity
      were significantly lower in patients with RA. During a manual task, delayed RTs
      and MTs were seen. Moreover, lower levels of balance confidence and more fear of
      falling were reported in patients with RA. There were no differences in activity
      levels. CONCLUSIONS: When performing a quick step, patients with RA show delayed
      MT and step velocity and decreased push off. Because quick stepping often is used
      to avoid falls, the increase in step execution time might have undesirable
      consequences. Furthermore, patients with RA have lower balance confidence and
      more fear of falling than healthy controls; these factors also contribute to
      higher fall risk.

PMID- 21872843
TI  - Resistance training dose response in combined endurance-resistance training in
      patients with cardiovascular disease: a randomized trial.
AB  - OBJECTIVE: To compare the effectiveness of 2 different volumes of resistance
      training (RT) combined with aerobic training in residential cardiac
      rehabilitation (CR). DESIGN: Randomized prospective cohort study. SETTING: Center
      for inpatient CR. PARTICIPANTS: Patients (N=295) with a mean age +/- SD of 62.7+/
      11.7 years participated in the study. INTERVENTIONS: Patients were randomly
      divided into 2 groups (group 1 and group 2) with different volumes of RT; 2 sets
      * 12 repetitions (REPS) (group 1) and 3 sets * 15 REPS (group 2) per session, 2
      times per week; each RT session consisting of 10 different resistance exercises.
      In addition, patients also completed continuous moderate intensity aerobic
      training composed of cycle ergometry 6 times per week for 17+/-4 minutes (mean +/
      SD) and walking 5 times per week for 45 minutes. MAIN OUTCOME MEASURES: At entry
      and after 26+/-4 (mean +/- SD) days of CR, blood pressure, heart rate, maximal
      oxygen consumption, and maximal power determined during cycle ergometry, strength
      determined via RT, and blood biochemistries were assessed. Data were analyzed via
      a 2-way (group * time) repeated measures analysis of variance. RESULTS:
      Statistical analysis revealed equivalent improvements in exercise capacity,
      muscular strength, hemodynamics, and blood chemistries regardless of RT volume
      (comparison-wise type I error rate, alpha<.01). CONCLUSIONS: Our results show
      that nearly doubling (3 sets * 15 REPS vs 2 sets * 12 REPS) the volume of RT as
      part of a residential CR program does not yield further improvement in strength
      and cardiovascular risk factors.

PMID- 21872844
TI  - Development and validation of a movement and activity in physical space score as
      a functional outcome measure.
AB  - OBJECTIVE: To develop and validate a functional measure, the Movement and
      Activity in Physical Space (MAPS) score, that encompasses both physical activity
      and environmental interaction. DESIGN: Observational matched-pair cohort with 2
      month follow-up. SETTING: General community under free-living conditions.
      PARTICIPANTS: Adult participants (N=18; n=9 postsurgical, n=9 matched control;
      mean age +/- SD, 28.9 +/- 12.0y) were monitored by an accelerometer and global
      positioning system receiver for 3 days within 1 week (4.1 +/- 2.8d) after knee
      surgery (T=0) and 2 months later (T+2). The healthy controls were matched for
      age, sex, smoking, perceived physical activity level, and occupation of a
      postsurgical participant. Correlation, t test (with Bonferroni adjustment:
      alpha=.05/2), analysis of variance, and intraclass correlation coefficient were
      used to establish validity and reliability evidence. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: MAPS scores. RESULTS: MAPS scores were
      moderately correlated with the Knee Injury and Osteoarthritis Outcome Score
      (P<.05). There was a significant group difference at T = 0 for MAPS (t(9.9)=
      3.60; P=.01). Analysis of variance results for the MAPS indicated a time and
      group interaction (F(1,12)=4.60, P=.05). Reliability of 3 days of MAPS scores
      ranged from 0.75 to 0.81 (postsurgical and control), and 2-month test-retest
      reliability in the control group was 0.94. CONCLUSIONS: The results provide a
      foundation of convergent and known-group difference validity evidence along with
      reliability evidence for the use of MAPS as a functional outcome measure.

PMID- 21872845
TI  - Intra- and interrater reliability and agreement of the Danish version of the
      Dynamic Gait Index in older people with balance impairments.
AB  - OBJECTIVES: To examine the intrarater and interrater reliability and agreement of
      the Danish version of the Dynamic Gait Index (DGI) in hospitalized and community
      dwelling older people with balance impairments. DESIGN: Reliability study.
      SETTING: University hospital and outpatient rehabilitation. PARTICIPANTS: A
      convenience sample of older people (>=65y); 24 subjects from a hospital and 24
      from an outpatient rehabilitation center. All subjects had either 1 or more falls
      within the last year or balance impairments evaluated by a physical therapist.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: All subjects carried out
      the DGI twice with a 1.5-hour interval. Each subject was rated by 3 physical
      therapists in the first attempt (1 for intrarater and 2 for interrater
      comparison) and by the intrarater in the second attempt, in both settings. The
      reliability was calculated using the intraclass correlation coefficient (ICC,
      2.1), while agreement was calculated as the smallest real difference (SRD).
      RESULTS: The ICC for intrarater and interrater reliability of the total DGI was
      .90 and .92 at the hospital, while the SRD was 2.72 and 2.58 points,
      respectively. Correspondingly, the ICC for intrarater and interrater reliability
      of the total DGI at the rehabilitation center was .89 and .82, while the SRD was
      3.49 and 3.99 points, respectively. CONCLUSIONS: The intrarater and interrater
      reliability of the total DGI ranged from good to excellent in hospitalized and
      community-dwelling older people. Improvements of 3 and 4 DGI points for
      hospitalized and community-dwelling older people, respectively, should be
      regarded as a real change (with a 95% certainty).

PMID- 21872846
TI  - Normalized muscle strength, aerobic capacity, and walking performance in chronic
      stroke: a population-based study on the potential for endurance and resistance
      training.
AB  - OBJECTIVES: To assess muscle strength, aerobic capacity, and walking performance
      compared with normative values in chronic hemiparetic stroke patients and,
      thereby, to investigate the potential for endurance and resistance training.
      Second, to study the relations between muscle strength, aerobic capacity, and
      walking performance using normalized test values. DESIGN: Population-based, cross
      sectional study. SETTING: University hospital, outpatient clinic. PARTICIPANTS:
      Patients (N=48) aged 50 to 80 years with reduced muscle strength and walking
      capacity due to an ischemic stroke 6 to 36 months prior to recruitment.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Peak oxygen consumption (Vo(2)peak)
      and isometric knee extensor muscle strength at the paretic knee were expressed as
      absolute and normalized values using normative data. The six-minute walk test
      (6MWT) and the habitual ten-meter walk test (10MWT) were secondary parameters.
      RESULTS: Peak Vo(2) was 77% (95% confidence interval [CI], 71-84) of the expected
      value, and the strength of the paretic knee was 71% (95% CI, 64-78), whereas
      walking speed (10MWT) was 59% (95% CI, 52-66) and walking distance (6MWT) was 59%
      (95% CI, 52-67). The normalized Vo(2)peak correlated to the normalized 6MWT
      (r=.58; P<.001) and normalized 10MWT (r=.53; P<.001). Normalized strength of the
      paretic knee correlated to normalized 6MWT (r=.40; P<.01) and normalized 10MWT
      (r=.31; P<.05). CONCLUSIONS: Lower extremity muscle strength and aerobic capacity
      are related to walking performance, which suggests a potential for endurance and
      resistance training in rehabilitation of walking performance in chronic
      hemiparesis after stroke. Correction for the influence of age, weight, and height
      providing normalized values improves the interpretation of severity of
      impairments and enables comparisons between patients.

PMID- 21872847
TI  - Withdrawal from chronic nicotine exposure alters dopamine signaling dynamics in
      the nucleus accumbens.
AB  - BACKGROUND: Unaided attempts to quit smoking commonly fail during the first 2
      weeks of the nicotine withdrawal syndrome. Alterations in dopamine (DA) signaling
      correlate with withdrawal from chronic nicotine exposure, but those changes have
      not been well-characterized. METHODS: Mice were administered nicotine in their
      drinking water for 4 or 12 weeks. Then nicotine was withheld for 1 to 10 days
      while DA signaling was characterized with in vivo microdialysis or fast-scan
      cyclic voltammetry. RESULTS: Upon withdrawal of nicotine, the basal DA
      concentration in the nucleus accumbens decreased as measured by microdialysis.
      The length of time that the low basal DA state lasted depended on the length of
      the chronic nicotine treatment. Microdialysis indicated that acute re-exposure to
      nicotine during withdrawal temporarily reversed this hypodopaminergic state.
      Voltammetry measurements supported the microdialysis results by showing that
      nicotine withdrawal decreased tonic and phasic DA release. The basal DA
      concentration and tonic DA signals, however, were disproportionately lower than
      the phasic DA signals. Therefore, the phasic/tonic DA signaling ratio was
      increased during the withdrawal period. CONCLUSIONS: The relative increase in the
      sensitivity of DA release to phasic stimulation suggests an increase in the
      signal-to-noise relationship of DA signaling during the withdrawal period.
      Therefore, the DA signal produced by acute nicotine re-exposure produces a DA
      response that might reinforce relapse to drug use (i.e., smoking). Because the
      basal DA concentration is low during withdrawal, therapies aimed at elevating the
      background DA signal represent a reasonable treatment strategy for nicotine
      dependent individuals attempting to quit.

PMID- 21872848
TI  - Early-life forebrain glucocorticoid receptor overexpression increases anxiety
      behavior and cocaine sensitization.
AB  - BACKGROUND: Genetic factors and early-life adversity are critical in the etiology
      of mood disorders and substance abuse. Because of their role in the transduction
      of stress responses, glucocorticoid hormones and their receptors could serve as
      both genetic factors and mediators of environmental influences. We have shown
      that constitutive overexpression of the glucocorticoid receptor (GR) in forebrain
      results in increased emotional reactivity and lability in mice. Here, we asked
      whether there was a critical period for the emergence of this phenotype. METHODS:
      We generated a mouse line with inducible GR overexpression specifically in
      forebrain. Anxiety-like behaviors and cocaine-induced sensitization were assessed
      in adult mice following GR overexpression during different periods in
      development. The molecular basis of the behavioral phenotype was examined using
      microarray analyses of dentate gyrus and nucleus accumbens. RESULTS: Transient
      overexpression of GR during early life led to increased anxiety and cocaine
      sensitization, paralleling the phenotype of lifelong GR overexpression. This
      increased emotional reactivity was not observed when GR overexpression was
      induced after weaning. Glucocorticoid receptor overexpression in early life is
      sufficient to alter gene expression patterns for the rest of the animal's life,
      with dentate gyrus being more responsive than nucleus accumbens. The altered
      transcripts are implicated in GR and axonal guidance signaling in dentate gyrus
      and dopamine receptor signaling in nucleus accumbens. CONCLUSIONS: Transient
      overexpression of GR early in life is both necessary and sufficient for inducing
      transcriptome-wide changes in the brain and producing a lifelong increase in
      vulnerability to anxiety and drugs of abuse.

PMID- 21872850
TI  - Oxygen therapy improves energy metabolism in focal cerebral ischemia.
AB  - Oxygen therapy (OT) with hyperbaric oxygen (HBO) or normobaric hyperoxia (NBO)
      improves the oxygenation of penumbral tissue in experimental ischemic stroke.
      However, whether this results in the improvement of energy metabolism is unclear.
      We investigated the effect of both OTs on tissue acidosis and on ATP production.
      Beginning 25 min after filament middle cerebral artery occlusion (MCAO), mice
      breathed either air, 100% O2 (NBO), or 100% O2 at 3 ata (HBO) for 60 min.
      Regional tissue pH was measured using the umbelliferone fluorescence. Regional
      ATP concentration was depicted by substrate-specific bioluminescence. Severity of
      ischemia did not differ among groups in laser-Doppler flowmetry. Both NBO (70.1+/
      14.0 mm3) and, more effectively, HBO (57.2+/-11.9 mm3) significantly reduced
      volume of tissue acidosis compared to air (89.4+/-4.0 mm3), p<0.05).
      Topographically, acidosis was less pronounced in the medial striatum and in the
      cortical ischemic border areas. This resulted in significantly smaller volumes of
      ATP depletion (77.8+/-7.7 mm3 in air, 61.4+/-15.2 mm3 in NBO and 51.2+/-14.4 mm3
      in HBO; p<0.05). In conclusion, OT significantly improves energy metabolism in
      the border zones of focal cerebral ischemia which are the areas protected by OT
      in this model.

PMID- 21872849
TI  - Abnormal tau, mitochondrial dysfunction, impaired axonal transport of
      mitochondria, and synaptic deprivation in Alzheimer's disease.
AB  - Growing evidence suggests that amyloid beta (Abeta) and tau pathologies are
      strongly associated with mitochondrial dysfunction and neuronal damage in
      Alzheimer's disease (AD). Extensive research of AD postmortem brains, mouse and
      fly models, including triple transgenic AD mice and mutant tau mice, and cell
      culture studies revealed that tau hyperphosphorylation is caused by multiple
      factors, including intraneuronal Abeta-oligomers, chronic oxidative stress,
      reduced insulin-like growth factor 1, and astrocytic mediated-Abeta and caspase
      activation. Overexpressed and phosphorylated tau appears to impair axonal
      transport of organelles causing synapse starvation, depletion of ATP, and
      ultimately neuronal damage. This article evaluates the role of tau in
      mitochondrial dysfunction and assesses how hyperphosphorylated tau impairs axonal
      transport of organelles in AD neurons.

PMID- 21872851
TI  - Kinetics and mechanism of permanganate oxidation of iota- and lambda-carrageenan
      polysaccharides as sulfated carbohydrates in acid perchlorate solutions.
AB  - The kinetics of oxidation of iota- and lambda-carrageenan as sulfated
      carbohydrates by permanganate ion in aqueous perchlorate solutions at a constant
      ionic strength of 2.0 mol dm(-3) have been investigated spectrophotometrically.
      The pseudo-first-order plots were found to be of inverted S-shape throughout the
      entire courses of reactions. The initial rates were found to be relatively slow
      in the early stages, followed by an increase in the oxidation rates over longer
      time periods. The experimental observations showed first-order dependences in
      permanganate and fractional first-order kinetics with respect to both
      carrageenans concentration for both the induction and autoacceleration periods.
      The results obtained at various hydrogen ion concentrations showed that the
      oxidation processes in these redox systems are acid-catalyzed throughout the two
      stages of oxidation reactions. The added salts lead to the prediction that
      Mn(III) is the reactive species throughout the autoacceleration periods. Kinetic
      evidence for the formation of 1:1 intermediate complexes was revealed. The
      kinetic parameters have been evaluated and tentative reaction mechanisms in good
      agreement with the kinetic results are discussed.

PMID- 21872853
TI  - Brain connectivity during resting state and subsequent working memory task
      predicts behavioural performance.
AB  - Brain regions simultaneously activated during any cognitive process are
      functionally connected, forming large-scale networks. These functional networks
      can be examined during active conditions [i.e., task-functional magnetic
      resonance imaging (fMRI)] and also in passive states (resting-fMRI), where the
      default mode network (DMN) is the most widely investigated system. The role of
      the DMN remains unclear, although it is known to be responsible for the shift
      between resting and focused attention processing. There is also some evidence for
      its malleability in relation to previous experience. Here we investigated brain
      connectivity patterns in 16 healthy young subjects by using an n-back task with
      increasing levels of memory load within the fMRI context. Prior to this working
      memory (WM) task, participants were trained outside fMRI with a shortened test
      version. Immediately after, they underwent a resting-state fMRI acquisition
      followed by the full fMRI n-back test. We observed that the degree of intrinsic
      correlation within DMN and WM networks was maximal during the most demanding n
      back condition (3-back). Furthermore, individuals showing a stronger negative
      correlation between the two networks under both conditions exhibited better
      behavioural performance. Interestingly, and despite the fact that we considered
      eight different resting-state fMRI networks previously identified in humans, only
      the connectivity within the posteromedial parts of the DMN (precuneus) prior to
      the fMRI n-back task predicted WM execution. Our results using a data-driven
      probabilistic approach for fMRI analysis provide the first evidence of a direct
      relationship between behavioural performance and the degree of negative
      correlation between the DMN and WM networks. They further suggest that in the
      context of expectancy for an imminent cognitive challenge, higher resting-state
      activity in the posteromedial parietal cortex may be related to increased
      attentional preparatory resources.

PMID- 21872852
TI  - Simulating ventilation distribution in heterogenous lung injury using a binary
      tree data structure.
AB  - To determine the impact of mechanical heterogeneity on the distribution of
      regional flows and pressures in the injured lung, we developed an anatomic model
      of the canine lung comprised of an asymmetric branching airway network, which can
      be stored as binary tree data structure. The entire tree can be traversed using a
      recursive flow divider algorithm, allowing for efficient computation of acinar
      flow and pressure distributions in a mechanically heterogeneous lung. These
      distributions were found to be highly dependent on ventilation frequency and the
      heterogeneity of tissue elastances, reflecting the preferential distribution of
      ventilation to areas of lower regional impedance.

PMID- 21872854
TI  - The prefrontal cortex: comparative architectonic organization in the human and
      the macaque monkey brains.
AB  - Detailed cytoarchitectonic studies of the human cerebral cortex appeared during
      the first quarter of the 20th century. The incorporation of the cytoarchitectonic
      map by Brodmann (1909) in the Talairach proportional stereotaxic space (Talairach
      and Tournoux, 1988) has established the Brodmann numerical nomenclature as the
      basis for describing the cortical location of structural and functional findings
      obtained with modern neuroimaging. In experimental anatomical and physiological
      investigations of the macaque monkey performed during the last 50 years, the
      numerical architectonic nomenclature used to describe findings in the prefrontal
      cortex has been largely based on the map by Walker (1940). Unfortunately, the map
      by Walker was not based on a comparative investigation of the cytoarchitecture of
      the human and macaque monkey prefrontal cortex and, as a result, the nomenclature
      and the criteria for demarcating areas in the two primate species are not always
      consistent. These discrepancies are a major obstacle in the ability to compare
      experimental findings from nonhuman primates with results obtained in functional
      and structural neuroimaging of the human brain. The present article outlines
      these discrepancies in the classical maps and describes comparative
      investigations of the cytoarchitecture of the prefrontal cortex of the macaque
      monkey and human (Petrides and Pandya, 1994, 1999, 2002a) in order to resolve
      these discrepancies and enable easy translation of experimental research in the
      monkey to findings in the human brain obtained with modern neuroimaging.

PMID- 21872855
TI  - Efficient decentralized iterative learning tracker for unknown sampled-data
      interconnected large-scale state-delay system with closed-loop decoupling
      property.
AB  - In this paper, an efficient decentralized iterative learning tracker is proposed
      to improve the dynamic performance of the unknown controllable and observable
      sampled-data interconnected large-scale state-delay system, which consists of N
      multi-input multi-output (MIMO) subsystems, with the closed-loop decoupling
      property. The off-line observer/Kalman filter identification (OKID) method is
      used to obtain the decentralized linear models for subsystems in the
      interconnected large-scale system. In order to get over the effect of modeling
      error on the identified linear model of each subsystem, an improved observer with
      the high-gain property based on the digital redesign approach is developed to
      replace the observer identified by OKID. Then, the iterative learning control
      (ILC) scheme is integrated with the high-gain tracker design for the
      decentralized models. To significantly reduce the iterative learning epochs, a
      digital-redesign linear quadratic digital tracker with the high-gain property is
      proposed as the initial control input of ILC. The high-gain property controllers
      can suppress uncertain errors such as modeling errors, nonlinear perturbations,
      and external disturbances (Guo et al., 2000) [18]. Thus, the system output can
      quickly and accurately track the desired reference in one short time interval
      after all drastically-changing points of the specified reference input with the
      closed-loop decoupling property.

PMID- 21872856
TI  - Blood cell salvage during cesarean delivery.
AB  - OBJECTIVE: To review the use of blood cell salvage performed during cesarean
      delivery. METHODS: A retrospective review of the case notes of 107 patients who
      underwent blood cell salvage during cesarean delivery. A total of 102 women at
      high risk of hemorrhage were prepared preoperatively for cell salvage. A second
      group of 5 patients had cell salvage initiated intraoperatively owing to
      unexpected severe hemorrhage. RESULTS: Of the 107 patients, 36 (33.6%) were re
      infused with salvaged blood. There were no reported incidents of amniotic
      embolization or hemolytic disease. Of the 31 patients for whom cell salvage was
      prepared preoperatively, only 6 patients required transfusion of banked blood. In
      elective procedures, patients were re-infused with salvaged blood averaging 28%
      of the volume of blood lost, without complications. CONCLUSION: Cell salvage was
      acceptable, beneficial, and without adverse events in both high-risk elective
      cesareans and emergency cesareans for unexpected hemorrhaging. The skills refined
      during use of cell salvage in elective cesareans were crucial for successful
      implementation during emergency situations.

PMID- 21872857
TI  - Effect of intravenous tranexamic acid administration on blood loss during and
      after cesarean delivery.
AB  - OBJECTIVE: To assess the effect of intravenous tranexamic acid on blood loss
      during and after cesarean delivery. METHODS: One hundred pregnant women were
      randomized to receive either 10 mg/kg of tranexamic acid or placebo intravenously
      20 minutes before incision in a double-blind controlled study. Postplacental
      delivery blood loss, postoperative hemorrhage 2 hours after surgery, and oxytocin
      administration were recorded. RESULTS: The patients' mean age, weight, and
      duration of surgery were similar between the 2 groups. Mean blood loss was
      significantly less in the tranexamic acid group compared with the control group
      for both intraoperative bleeding (262.5 +/- 39.6 vs 404.7 +/- 94.4 mL) and
      postoperative bleeding (67.1 +/- 6.5 vs 141.0 +/- 33.9 mL; P<0.001),
      respectively. Oxytocin administration was significantly less in the tranexamic
      acid group compared with the control group (39 +/- 5.8 vs 43 +/- 5.4 units;
      P=0.001). CONCLUSION: Intravenous tranexamic acid decreased intra- and
      postoperative blood loss and oxytocin administered in patients delivered by
      cesarean.

PMID- 21872858
TI  - The combination of mifepristone and misoprostol for the termination of pregnancy.
AB  - The combination of 200mg of mifepristone followed by 25 MUg to 800 MUg (depending
      on gestational age) of misoprostol has been shown to be effective for the
      termination of pregnancy throughout gestation. The dose of misoprostol should be
      reduced as gestational age increases. Mifepristone is not indicated for induction
      of labor with a live fetus because there are no data to confirm that it does not
      have a possible deleterious fetal effect. The course of treatment and
      prerequisites for medical abortion and recommended mifepristone and misoprostol
      regimens for different gestational ages are described, along with the side
      effects, management of complications, and postabortion care. The use of the
      mifepristone-misoprostol combination regimen for induction of labor in cases of
      fetal death is also described.

PMID- 21872859
TI  - Visceral adiposity after tibolone use.
AB  - OBJECTIVE: To evaluate the differences in visceral fat between women using
      tibolone and those not using tibolone. METHODS: Sixty-five healthy postmenopausal
      women were included in the study: 26 who were taking tibolone (2.5 mg/day); and
      39 who were not receiving tibolone treatment. Anthropometric measurements were
      performed, with subcutaneous and visceral fat measured via ultrasound.
      Differences between the groups were determined via Student t test. RESULTS: There
      were no significant differences in age (P=0.796), weight (P=0.256), height
      (P=0.456), body mass index (P=0.08), waist circumference (P=0.420), or waist-hip
      ratio (P=0.1) between the groups. Hip circumference was significantly lower in
      the study group than in the control group (97.7 +/- 12.2 cm vs 103 +/- 8.1cm;
      P<0.04). There were no significant differences between the groups in subcutaneous
      fat measurements (P=0.56). There were significantly lower visceral fat
      measurements (2.8 +/- 1.1cm vs 3.9 +/- 1.6 cm; P<0.004) and a significantly lower
      visceral fat-subcutaneous fat ratio (1.1 +/- 0.3 vs 1.5 +/- 0.7; P<0.005) in the
      study group than in the control group. CONCLUSION: Postmenopausal women who use
      tibolone have lower visceral fat measurements than do woman of similar age who do
      not use tibolone.

PMID- 21872860
TI  - Macroscopic appearance of a uterus with a cesarean scar pregnancy.

PMID- 21872861
TI  - Low plasma levels of the soluble receptor for advanced glycation end products in
      HIV-infected patients with subclinical carotid atherosclerosis receiving combined
      antiretroviral therapy.
AB  - OBJECTIVE: Combined antiretroviral therapy (cART) has significantly improved the
      survival rate and quality of life for HIV-infected subjects, but it contributes
      to the development of metabolic complications including coronary artery disease
      (CAD). Recent studies have reported that high plasma levels of the soluble
      receptor for advanced glycation end products (sRAGE) were associated with a lower
      incidence of CAD in non-HIV infected patients. However, there has been no report
      of an association of sRAGE and subclinical carotid atherosclerosis in HIV
      infected patients receiving cART. METHODS: We examined the association of
      circulating sRAGE in HIV-infected patients with carotid intima-media thickness
      (IMT) and other metabolic variables. We prospectively enrolled 76 HIV-infected
      patients receiving cART for >= 6 months. RESULTS: sRAGE had a significantly
      negative correlation with body mass index (r = -0.324, p = 0.005), waist-to-hip
      ratio (r = -0.335, p = 0.003), systolic blood pressure (BP) (r=-0.359, p=0.002),
      diastolic BP (r = -0.343, p = 0.004), total cholesterol (r = -0.240, p = 0.037),
      low-density lipoprotein-cholesterol (r=-0.284, p=0.024), log(homeostasis model
      assessment of insulin resistance [HOMA-IR]) (r = -0.380, p = 0.002) and carotid
      IMT including max-IMT and mean-IMT (r = -0.358, p = 0.001 and r = -0.329, p =
      0.004, respectively). By the use of multiple stepwise regression analyses,
      systolic BP (p=0.001) and log[HOMA-IR] (p = 0.001) remained significant
      independently. CONCLUSIONS: These results suggest that sRAGE may have a
      protective effect against subclinical atherosclerosis by preventing inflammatory
      responses mediated by the activation of cell surface RAGE in HIV-infected
      patients receiving cART.

PMID- 21872862
TI  - Head impact exposure in collegiate football players.
AB  - In American football, impacts to the helmet and the resulting head accelerations
      are the primary cause of concussion injury and potentially chronic brain injury.
      The purpose of this study was to quantify exposures to impacts to the head
      (frequency, location and magnitude) for individual collegiate football players
      and to investigate differences in head impact exposure by player position. A
      total of 314 players were enrolled at three institutions and 286,636 head impacts
      were recorded over three seasons. The 95th percentile peak linear and rotational
      acceleration and HITsp (a composite severity measure) were 62.7g, 4378rad/s(2)
      and 32.6, respectively. These exposure measures as well as the frequency of
      impacts varied significantly by player position and by helmet impact location.
      Running backs (RB) and quarter backs (QB) received the greatest magnitude head
      impacts, while defensive line (DL), offensive line (OL) and line backers (LB)
      received the most frequent head impacts (more than twice as many than any other
      position). Impacts to the top of the helmet had the lowest peak rotational
      acceleration (2387rad/s(2)), but the greatest peak linear acceleration (72.4g),
      and were the least frequent of all locations (13.7%) among all positions. OL and
      QB had the highest (49.2%) and the lowest (23.7%) frequency, respectively, of
      front impacts. QB received the greatest magnitude (70.8g and 5428rad/s(2)) and
      the most frequent (44% and 38.9%) impacts to the back of the helmet. This study
      quantified head impact exposure in collegiate football, providing data that is
      critical to advancing the understanding of the biomechanics of concussive
      injuries and sub-concussive head impacts.

PMID- 21872863
TI  - The effects of bone and pore volume fraction on the mechanical properties of
      PMMA/bone biopsies extracted from augmented vertebrae.
AB  - Vertebroplasty forms a porous PMMA/bone composite which was shown to be weaker
      and less stiff than pure PMMA. It is not known what determines the mechanical
      properties of such composites in detail. This study investigated the effects of
      bone volume fraction (BV/TV), cement porosity (PV/(TV-BV), PV...pore volume) and
      cement stiffness. Nine human vertebral bodies were augmented with either standard
      or low-modulus PMMA cement and scanned with a HR-pQCT system before and after
      augmentation. Fourteen cylindrical PMMA/bone biopsies were extracted from the
      augmented region, scanned with a micro-CT system and tested in compression until
      failure. Micro-finite element (FE) models of the complete biopsies, of the
      trabecular bone alone as well as of the porous cement alone were generated from
      CT images to gain more insight into the role of bone and pores. PV/(TV-BV) and
      experimental moduli of standard/low-modulus cement (R(2)=0.91/0.98) as well as
      PV/(TV-BV) and yield stresses (R(2)=0.92/0.83) were highly correlated. No
      correlation between BV/TV (ranging from 0.057 to 0.138) and elastic moduli was
      observed (R(2)< 0.05). Interestingly, the micro-FE models of the porous cement
      alone reproduced the experimental elastic moduli of the standard/low-modulus
      cement biopsies (R(2)=0.75/0.76) more accurately than the models with bone
      (R(2)=0.58/0.31). In conclusion, the mechanical properties of the biopsies were
      mainly determined by the cement porosity and the cement material properties. The
      study showed that bone tissue inside the biopsies was mechanically "switched off"
      such that load was carried essentially by the porous PMMA.

PMID- 21872864
TI  - Stir bar sorptive extraction and comprehensive two-dimensional gas chromatography
      coupled to high-resolution time-of-flight mass spectrometry for ultra-trace
      analysis of organochlorine pesticides in river water.
AB  - A method for the determination of ultra-trace amounts of organochlorine
      pesticides (OCPs) in river water was developed by using stir bar sorptive
      extraction (SBSE) followed by thermal desorption and comprehensive two
      dimensional gas chromatography coupled to high-resolution time-of-flight mass
      spectrometry (SBSE-TD-GC*GC-HRTOF-MS). SBSE conditions such as extraction time
      profiles, phase ratio (beta: sample volume/polydimethylsiloxane (PDMS) volume),
      and modifier addition, were examined. Fifty milli-liter sample including 10%
      acetone was extracted for 3 h using stir bars with a length of 20 mm and coated
      with a 0.5 mm layer of PDMS (PDMS volume, 47 MUL). The stir bar was thermally
      desorbed and subsequently analyzed by GC*GC-HRTOF-MS. The method showed good
      linearity over the concentration range from 50 to 1000 pg L(-1) or 2000 pg L(-1)
      for all analytes, and the correlation coefficients (r(2)) were greater than
      0.9903 (except for beta-HCH, r(2)=0.9870). The limit of detection (LOD) ranged
      from 10 to 44 pg L(-1). The method was successfully applied to the determination
      of 16 OCPs at pg L(-1) to ng L(-1) in river water. The results agree fairly well
      with the values obtained by a conventional liquid-liquid extraction (LLE)-GC-HRMS
      (selected ion monitoring: SIM) method using large sample volume (20 L). The
      method also allows screening of non-target compounds, e.g. pesticides and their
      degradation products, polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls
      (PCBs), and pharmaceuticals and personal care products (PPCPs) and metabolites in
      the same river water sample, by using full spectrum acquisition with accurate
      mass in GC*GC.

PMID- 21872865
TI  - Contributions to reversed-phase column selectivity. II. Cation exchange.
AB  - The contribution of cation exchange to solute retention for type-B alkylsilica
      columns (made from high-purity silica) has been examined in terms of the
      hydrophobic-subtraction (H-S) model of reversed-phase column selectivity. The
      relative importance of cation exchange in the separation of ionized bases by
      reversed-phase chromatography (RPC) varies with (a) column acidity (values of the
      column cation-exchange capacity C), (b) mobile-phase pH and buffer concentration,
      and (c) the nature of the buffer cation. The effects of each of these separation
      variables on cation retention were examined. The contribution of cation exchange
      (and other ionic interactions) to solute retention is represented in the H-S
      model by properties of the solute (kappa') and column (C), respectively. Values
      of kappa' for 87 solutes have been examined as a function of solute molecular
      structure, and values of C for 167 type-B alkylsilica columns have been related
      to various column properties: ligand length (e.g., C(8) vs. C(18)) and
      concentration (MUmol/m(2)), pore diameter (nm), and end-capping. These results
      contribute to a more detailed picture of the retention of cationic solutes in RPC
      as a function of separation conditions. While previous work suggests that the
      ionization of type-B alkylsilica columns is generally negligible with mobile
      phase pH<7 (as a result of which cation exchange then becomes insignificant), the
      present study provides evidence for cation exchange (and presumably silanol
      ionization) at a pH as low as 3 for most columns.

PMID- 21872866
TI  - Comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry
      for the identification of organobrominated compounds in bluefin tuna.
AB  - This study evaluates comprehensive two-dimensional gas chromatography (GC*GC)
      coupled to time-of-flight mass spectrometry (GC*GC-ToF MS) for the simultaneous
      analysis of several classes of organobromines (OBs), including polybrominated
      diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), methoxylated PBDEs (MeO
      PBDEs), several halogenated naturally produced compounds (HNPs) and eight novel
      brominated flame retardants (NBFRs), polybrominated hexahydroxanthene derivates
      (PBHDs), 2,4,6-tribromoanisole and a mixed halogenated compound (MHC-1), in
      bluefin tuna muscles. The proposed methodology maximised separation of both
      within and among OB families, and among these and other halogenated
      micropollutants detected in these samples and co-extracted matrix components.
      Special attention has been paid to solve co-elution problems observed during the
      analysis of OBs with one-dimensional GC-based techniques. Satisfactory separation
      among several relevant PBDEs and MeO-PBDEs has been obtained allowing their
      unambiguous determination in a single run. Additional studies were conducted to
      identify selected NBFRs and HNPs. 2,4-Dibromoanisole, a dibromophenol isomer and
      hexabromobenzene were identified in the investigated samples. Several new tri-
      and tetra-BHD derivates were also identified, indicating that these compounds
      could apparently exist as structured families in nature. In addition, a
      tetrabrominated diMeO-biphenyl and two tetrabrominated diMeO-BDEs were also
      tentatively identified.

PMID- 21872867
TI  - Development of melamine certified reference material in milk using two different
      isotope dilution mass spectrometry techniques.
AB  - A new certified reference material (CRM) of melamine in milk GLHK-11-02 was
      developed aiming to address the great demand from the testing community after the
      melamine crises. The material was prepared by adding an appropriate quantity of
      melamine into the skimmed milk samples and the final product was in the form of
      fine lyophilized powder. Characterization of the material relied on two newly
      developed gravimetric isotope dilution mass spectrometry (IDMS) methods, one
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and another gas
      chromatography-mass spectrometry (GC-MS). Experimental parameters with crucial
      effects on the performance of the two IDMS methods were thoroughly investigated.
      These included purity of standard used, equilibration time of isotopes,
      efficiency of extraction methods as well as possible interferences from the
      matrix and melamine analogues. Precision was found to be excellent with a
      coefficient of variation of 2.5% for the LC-IDMS/MS (n=46) and 1.9% for the GC
      IDMS (n=30) respectively. Using one-tail Student's t-test at 95% confidence
      interval, analytical data sets generated from the two methods were found to
      exhibit no significant difference. Measurement accuracy of the methods was
      further verified through an Asia Pacific Metrology Program (APMP) pilot study.
      Analytical results of the present LC-IDMS/MS for the two milk test samples at the
      concentration level of about 0.45 and 3.5 mg kg(-1) were proven to be very good.
      There were excellent overlaps between our results and the assigned reference
      values, and the absolute deviation was less than 3.2%. Both the LC-IDMS/MS and GC
      IDMS methods were shown to be sufficiently reliable and accurate for
      certification of the melamine CRM. Certified value of melamine in dry mass
      fraction in GLHK-11-02 was 1.14 mg kg(-1). Expanded uncertainty due to sample
      inhomogeneity, long term and short term stability and variability in the
      characterization procedure was at 7.1% or 0.08 mg kg(-1). The CRM is primarily
      used to provide a complete method validation for and to improve the technical
      competence of melamine analysis to food and chemical testing laboratories.

PMID- 21872868
TI  - A novel graphene nanosheets coated stainless steel fiber for microwave assisted
      headspace solid phase microextraction of organochlorine pesticides in aqueous
      samples followed by gas chromatography with electron capture detection.
AB  - In this study, a novel graphene nanosheets (GNSs) coated solid phase
      microextraction (SPME) fiber was prepared by immobilizing microwave synthesized
      GNSs on a stainless steel wire. Microwave synthesized GNSs were verified by X-ray
      diffraction, field emission-scanning electron microscopy (FE-SEM) and
      transmission electron microscope (TEM). GNS-SPME fiber was characterized using FE
      SEM and the results showed the GNS coating was homogeneous, porous, and highly
      adherent to the surface of the stainless steel fiber. The performance and
      feasibility of the GNS-SPME fiber was evaluated under one-step microwave assisted
      (MA) headspace (HS) SPME followed by gas chromatography with electron capture
      detection for five organochlorine pesticides (OCPs) in aqueous samples.
      Parameters influencing the extraction efficiency of MA-HS-GNS-SPME such as
      microwave irradiation power and time, pH, ionic strength, and desorption
      conditions were thoroughly examined. Under the optimized conditions, detection
      limits for the OCPs varied between 0.16 and 0.93 ng L(-1) and linear ranges
      varied between 1 and 1500 n gL(-1), with correlation coefficients ranging from
      0.9984 to 0.9998, and RSDs in the range of 3.6-15.8% (n=5). In comparison with
      the commercial 100 MUm polydimethylsiloxane fiber, the GNS coated fiber showed
      better extraction efficiency, higher mechanical and thermal stability (up to 290
      degrees C), longer life span (over 250 times), and lower production cost. The
      method was successfully applied to the analysis of real water samples with
      recoveries ranged between 80.1 and 101.1% for river water samples. The results
      demonstrated that the developed MA-HS-GNS-SPME method was a simple, rapid,
      efficient pretreatment and environmentally friendly procedure for the analysis of
      OCPs in aqueous samples.

PMID- 21872869
TI  - A theory-based approach to thermal field-flow fractionation of polyacrylates.
AB  - A theory-based approach is presented for the development of thermal field-flow
      fractionation (ThFFF) of polyacrylates. The use of ThFFF for polymer analysis has
      been limited by an incomplete understanding of the thermal diffusion which plays
      an important role in retention and separation. Hence, a tedious trial-and-error
      approach to method development has been the normal practice when analyzing new
      materials. In this work, thermal diffusion theories based on temperature
      dependent osmotic pressure gradient and polymer-solvent interaction parameters
      were used to estimate thermal diffusion coefficients (D(T)) and retention times
      (t(r)) for different polymer-solvent pairs. These calculations identified methyl
      ethyl ketone as a solvent that would cause significant retention of poly(n-butyl
      acrylate) (PBA) and poly(methyl acrylate) (PMA). Experiments confirmed retention
      of these two polymers that have not been previously analyzed by ThFFF.
      Theoretical and experimental D(T)s and t(r)s for PBA, PMA, and polystyrene in
      different solvents agreed to within 20% and demonstrate the feasibility of this
      theory-based approach.

PMID- 21872870
TI  - Comparison of charge state distribution in commercially available sulfated
      cyclodextrins used as chiral resolving agents in capillary electrophoresis.
AB  - The charge state distributions of randomly sulfated cyclodextrins from Sigma
      Aldrich and Beckman-Coulter, as well as single isomer sulfated cyclodextrins from
      TM Chemicals LP were investigated using hydrophilic interaction liquid
      chromatography (HILIC). A cross-linked diol phase and an unbonded silica phase
      were used as HILIC stationary phases. Groups of sulfated cyclodextrins with
      different charge states were resolved from each other, while regioisomers in a
      charge group were partially separated. A ladder of sulfated cyclodextrins having
      a charge state distribution from 1 to 14 was prepared and was used to determine
      the charge state heterogeneity of the commercially available sulfated
      cyclodextrin samples. Wide charge state and regioisomer distributions are seen
      for the randomly sulfated cyclodextrins, while HILIC analysis of every single
      isomer sulfated cyclodextrin sample indicates the presence of a single species.

PMID- 21872871
TI  - Characterization of interaction kinetics between chiral solutes and human serum
      albumin by using high-performance affinity chromatography and peak profiling.
AB  - Peak profiling and high-performance columns containing immobilized human serum
      albumin (HSA) were used to study the interaction kinetics of chiral solutes with
      this protein. This approach was tested using the phenytoin metabolites 5-(3
      hydroxyphenyl)-5-phenylhydantoin (m-HPPH) and 5-(4-hydroxyphenyl)-5
      phenylhydantoin (p-HPPH) as model analytes. HSA columns provided some resolution
      of the enantiomers for each phenytoin metabolite, which made it possible to
      simultaneously conduct kinetic studies on each chiral form. The dissociation rate
      constants for these interactions were determined by using both the single flow
      rate and multiple flow rate peak profiling methods. Corrections for non-specific
      interactions with the support were also considered. The final estimates obtained
      at pH 7.4 and 37 degrees C for the dissociation rate constants of these
      interactions were 8.2-9.6 s(-1) for the two enantiomers of m-HPPH and 3.2-4.1 s(
      1) for the enantiomers of p-HPPH. These rate constants agreed with previous
      values that have been reported for other drugs and solutes that have similar
      affinities and binding regions on HSA. The approach used in this report was not
      limited to phenytoin metabolites or HSA but could be applied to a variety of
      other chiral solutes and proteins. This method could also be adopted for use in
      the rapid screening of drug-protein interactions.

PMID- 21872872
TI  - Headspace-solid phase microextraction coupled to gas chromatography-combustion
      isotope ratio mass spectrometer and to enantioselective gas chromatography for
      strawberry flavoured food quality control.
AB  - Authenticity assessment of flavoured strawberry foods was performed using
      headspace-solid phase microextraction (HS-SPME) coupled to gas chromatography
      combustion-isotope ratio mass spectrometry (GC-C-IRMS). An authenticity range was
      achieved, investigating on the carbon isotope ratio of numerous selected aroma
      active volatile components (methyl butanoate, ethyl butanoate, hex-(2E)-enal,
      methyl hexanoate, buthyl butanoate, ethyl hexanoate, hexyl acetate, linalool,
      hexyl butanoate, octyl isovalerate, gamma-decalactone and octyl hexanoate) of
      organic Italian fresh strawberries. To the author's knowledge, this is the first
      time that all these components were investigated simultaneously by GC-C-IRMS on
      the same sample. The results were compared, when applicable, with those obtained
      by analyzing the HS-SPME extracts of commercial flavoured food matrices. In
      addition, one Kenyan pineapple and one fresh Italian peach were analyzed to
      determine the delta(13)C(VPDB) of the volatile components common to strawberry.
      The delta(13)C(VPDB) values are allowed to differentiate between different
      biogenetic pathways (C(3) and CAM plants) and more interestingly between plants
      of the same CO(2) fixation group (C(3) plants). Additional analyses were
      performed on all the samples by means of Enantioselective Gas Chromatography (Es
      GC), measuring the enantiomeric distribution of linalool and gamma-decalactone.
      It was found that GC-C-IRMS and Es-GC measurements were in agreement to detect
      the presence of non-natural strawberry aromas in the food matrices studied.

PMID- 21872873
TI  - Advancing liquid/liquid extraction through a novel microfluidic device: theory,
      instrumentation and applications in gas chromatography.
AB  - A new chip-based liquid-liquid extraction technique for sample preparation of
      aqueous samples for GC was developed. Extraction is performed in a segmented flow
      system with additional mixing provided by an etched channel structure. The
      dimensions of the device are optimized to allow benefiting of the advantages of
      chip technology without suffering from the limitations of over-miniaturization.
      Phase separation is performed with a novel phase separator developed in house.
      The instrumental set-up is simple. The results obtained for selected test
      analytes show that the extraction is quantitative (recoveries = 92-110%, RSD <
      6%) for a wide range of hydrophobicities (LogK(o/w) = 0.86-4.79). The performance
      at different flow rates (0.5-6.0 mL/min) and flow ratios (beta = 1-10) was
      evaluated, confirming the flexibility and the possibility to perform enrichment.
      The results obtained for a few selected applications demonstrate the suitability
      of the method to perform quick, simple and reliable sample preparation for
      analytes of interest in real samples.

PMID- 21872874
TI  - The current revolution in column technology: how it began, where is it going?
AB  - This work revisits the exceptionally rapid evolution of the technology of
      chromatographic columns and the important progress in speed of analysis and
      resolution power that was achieved over the last ten years. Whereas columns
      packed with 10 and 5 MUm fully porous particles dominated the field for nearly
      thirty years (1975-2000), it took barely six years to see the commercialization
      of monolithic silica rods (2000), their raise to fame and decay to oblivion, the
      development of finer fully porous particles with size down to 1.7 MUm (2006), and
      of sub-3 MUm superficially porous particles (2006). Analysis times and plate
      heights delivered by columns packed with these recent packing materials have then
      been improved by more than one order of magnitude in this short period of time.
      This progress has rendered practically obsolete the age-old design of LC
      instruments. For low molecular weight compounds, analysts can now achieve peak
      capacities of 40 peaks in about 15s with a hold-up time of the order of 1.5s , in
      gradient elution, by operating columns packed with sub-3 MUm shell particles at
      elevated temperatures, provided that they use optimized high pressure liquid
      chromatographs. This is the ultimate limit allowed by modern instruments, which
      have an extra-column band broadening contribution of 7 MUL2 at 4.0 mL/min and
      data acquisition rate of 160 Hz. The best 2.1 mm * 50 mm narrow-bore columns
      packed with 1.7 MUm silica core-shell particles provide peaks that have a
      variance of 2.1 MUL2 for k=1. Finally, this work discusses possible ways to
      accelerate separations and, in the same time perform these separations at the
      same level of efficiency as they have today. It seems possible to pack columns
      with smaller particles, probably down to 1 MUm and operate them with current
      vHPLC equipments for separations of biochemicals. Analyses of low molecular
      weight compounds will require new micro-HPLC systems able to operate 1mm I.D.
      columns at pressures up to 5 kbar, which would eliminate the heat friction
      problems, and providing extra-column band broadening contributions smaller than
      0.1 MUL2. Alternatively, a new generation of vHPLC systems with minimal extra
      column contributions of less than 0.5 MUL2 could run 2.1mm I.D. columns if these
      latter were to be packed with high heat conductivity materials such as core-shell
      particles made with an alumina or gold core.

PMID- 21872875
TI  - Why ultra high performance liquid chromatography produces more tailing peaks than
      high performance liquid chromatography, why it does not matter and how it can be
      addressed.
AB  - The purpose of this study is to demonstrate, with experiments and with computer
      simulations based on a firm chromatographic theory, that the wide spread
      perception of that the United States Pharmacopeia tailing factor must be lower
      than 2 (T(f)<2) is questionable when using the latest generation of LC equipment.
      It is shown that highly efficient LC separations like those obtained with sub-2
      MUm porous and 2.7 MUm superficially porous particles (UHPLC) produce
      significantly higher T(f)-values than the corresponding separation based on 3 MUm
      porous particles (HPLC) when the same amount of sample is injected. Still UHPLC
      separations provide a better resolution to adjacent peaks. Expressions have been
      derived that describe how the T(f)-value changes with particle size or number of
      theoretical plates. Expressions have also been derived that can be used to scale
      the injection volume based on particle size or number of theoretical plates to
      maintain the T(f)-value when translating a HPLC separation to the corresponding
      UHPLC separation. An aspect that has been ignored in previous publications.
      Finally, data obtained from columns with different age/condition indicate that
      T(f)-values should be complemented by a peak width measure to provide a more
      objective quality measure.

PMID- 21872876
TI  - Identification of thioketone analogues of sildenfil using gas chromatography-mass
      spectrometry.
AB  - Sildenafil analogues have been found adulterated in herbal preparations and food
      products that claim to have natural aphrodisiacs. In this study, a gas
      chromatography-mass spectrometry (GC-MS) assay was developed for the screening
      and identification of thioketone analogues of sildenafil. Thiopyrazolopyrimidine,
      a precursor or a cleavage product of thioketone analogue, exhibited
      characteristic fragment ions of m/z 328 and m/z 299 was found to be the best
      marker to screen the presence of general thioketone analogues. Identification by
      GC-MS assay was rapid and specific as all the studied thioketones showed
      characteristic mass fragmentations including their intact molecular ions. The
      developed GC-MS assay had successfully identified thiosildenafil,
      thiohomosildenafil and thiodimethylsildenafil in herbal preparation and food
      products.

PMID- 21872877
TI  - The effects of aspect ratio of inorganic fillers on the structure and property of
      composite ion-exchange membranes.
AB  - A new type of nanocomposite ion-exchange membranes containing sulfonated
      polyethersulfone (sPES) polymer matrix and sulfonated surface-functionalized
      mesoporous silica (SS) inorganic fillers was prepared. Various characterizations
      revealed that the addition of inorganic fillers with different shapes had a
      significant influence on the membrane structure. The mesoporous inorganic fillers
      not only created extra pore and water channels, assisting the ionic migration and
      improving conductivity of the composites, but also provided additional fixed
      charge groups upon surface modification. This allows the Donnan exclusion to work
      effectively and thus improve the selectivity of membranes. It was proved that the
      incorporation of appropriate amount of SS additive could significantly improve
      the conductivity (up to 20 folds) and permselectivity (about 14%) of the sPES
      membranes. The performance of these newly developed membranes in desalination by
      electrodialysis was comparable with that of a commercial membrane (FKE).

PMID- 21872878
TI  - Length-controlled synthesis of oriented single-crystal rutile TiO2 nanowire
      arrays.
AB  - A free-standing, large area, oriented single-crystal rutile TiO(2) nanowire
      arrays with a controlled length in the range of 10-80 MUm are prepared via a
      facile one-step synthesis. The growth process is studied systematically in an
      appropriate amount of H(2)O(2) and HCl solution under hydrothermal conditions.
      The length of the nanowires can be easily tuned by varying the experimental
      parameters, including reaction temperature and reaction time. High-resolution
      transmission electron microscopy demonstrated that the nanowires have single
      crystal structure. Furthermore, the photoluminescence characteristics and
      photocatalytic properties of oriented single-crystal rutile TiO(2) nanowires was
      discussed in this paper, respectively. It is found that the increased reaction
      temperature is helpful to photocatalytic reactivity and photoluminescence
      properties.

PMID- 21872879
TI  - Mechanism underlying catecholaminergic polymorphic ventricular tachycardia and
      approaches to therapy.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited
      arrhythmia syndrome characterized by VT induced by adrenergic stress in the
      absence of structural heart disease and high incidence of sudden cardiac death.
      The diagnosis is made based on reproducible ventricular tachyarrhythmias
      including bidirectional VT and polymorphic VT during exercise testings. Two
      causative genes of CPVT have been identified: RYR2, encoding the cardiac
      ryanodine receptor (RyR2) Ca(2+) release channel, and CASQ2, encoding cardiac
      calsequestrin. A mutation in RYR2 or CASQ2 is identified in approximately 60% of
      patients with CPVT. Mutations in these two genes destabilize the RyR2 Ca(2+)
      release channel complex in sarcoplasmic reticulum and result in spontaneous
      Ca(2+) release through RyR2 channels leading to delayed after depolarization,
      triggered activity, and bidirectional/polymorphic VT. Implantable cardioverter
      defibrillators (ICDs) are recommended for prevention of sudden death in patients
      with CPVT.1. A.E. Epstein, J.P. DiMarco, K.A. Ellenbogen, et al., ACC/AHA/HRS
      2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a
      report of the American College of Cardiology/American Heart Association Task
      Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002
      Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia
      Devices): developed in collaboration with the American Association for Thoracic
      Surgery and Society of Thoracic Surgeons. Circulation. 2008;117:e350 However,
      painful shocks can trigger further adrenergic stress and arrhythmias, and deaths
      have occurred despite appropriate ICD shocks. Treatment with beta-adrenergic
      blockers reduces arrhythmia burden and mortality, but is not completely
      effective. The beneficial effects of Ca(2+) channel blocker verapamil in
      combination with beta-blocker have been reported, but the role of verapamil has
      not been well assessed. Because Ca(2+) leakage through ryanodine channel is a
      common mechanism of CPVT, ryanodine channel block may have a therapeutic effect.
      We discovered that flecainide directly inhibits RyR2 channels and prevent CPVT.
      Left cardiac sympathetic denervation may be an effective alternative treatment in
      combination with ICD, especially for patients whose arrhythmias are not
      controlled by drug therapies.

PMID- 21872880
TI  - Intestinal lymph-borne factors induce lung release of inflammatory mediators and
      expression of adhesion molecules after an intestinal ischemic insult.
AB  - BACKGROUND: Intestinal ischemia and reperfusion (I/R) is a documented cause of
      acute lung injury (ALI) and systemic inflammation. We previously reported that
      obstruction of thoracic lymphatic flow during intestinal I/R blunts pulmonary
      neutrophil recruitment and microvascular injury and decreases the systemic levels
      of tumor necrosis factor. Here, we consider the existence of a gut-lung axis
      promoting the induction of systemic inflammation, whereby drained intestinal
      lymph stimulates lung expression of adhesion molecules and matrix components and
      generation of inflammatory mediators. MATERIAL AND METHODS: Upon administration
      of anesthesia, male Wistar rats were subjected to occlusion of the superior
      mesenteric artery for 45 min, followed by 2 h of intestinal reperfusion (I/R);
      groups of rats were subjected to I/R with or without thoracic lymphatic duct
      ligation immediately before the procedure. The non-manipulated rats were used to
      investigate basal parameters. RESULTS: Obstruction of thoracic lymphatic flow
      before intestinal I/R decreased the ability of cultured lung tissue explants to
      release IL-1beta, IL-10, and VEGF. In contrast, lymphatic obstruction normalized
      the elevated lung expression of PECAM-1 caused by intestinal I/R. On the other
      hand, lung E-selectin expression was significantly reduced, whereas fibronectin
      expression and collagen synthesis were not affected. Lymph levels of LTB(4) and
      TXB(2) were found to be significantly increased. CONCLUSIONS: These data suggest
      that lymph factors drained from the intestine during ischemic trauma stimulate
      the lung to generate inflammatory mediators and alter the expression of adhesion
      molecules. Disturbances in lung homeostasis mediated by lymph might contribute to
      the spread of inflammatory processes, thereby accounting for the systemic
      inflammation induced by intestinal I/R.

PMID- 21872881
TI  - Pre-hospital hypothermia is not associated with increased survival after
      traumatic brain injury.
AB  - BACKGROUND: Conclusions from in vivo and in vitro studies suggest hypothermia may
      be protective in traumatic brain injury (TBI). Few studies evaluated the effect
      of admission temperature on outcomes. The purpose of this study is to examine the
      relationship between admission hypothermia and mortality in patients with
      isolated, blunt, moderate to severe TBI. METHODS: The Los Angeles Trauma Database
      was queried for all patients >= 14 y of age with isolated, blunt, moderate to
      severe TBI (head abbreviated injury score (AIS) >= 3, all other <3), admitted
      between 2005 and 2009. The study population was then stratified into two groups
      by admission temperature: hypothermic (<= 35 degrees C) and normothermic (>35
      degrees C). Demographic characteristics and outcomes were compared between
      groups. Logistic regression analysis was used to determine the relationship
      between admission hypothermia and mortality. RESULTS: A total of 1834 patients
      were analyzed and then stratified into two groups: hypothermic (n = 44) and
      normothermic (n = 1790). There was a significant difference noted in overall
      mortality (25% versus 7%), with the hypothermic group being four times more
      likely to succumb to their injuries. After adjusting for confounding factors,
      admission hypothermia was independently associated with increased mortality (AOR
      2.5; 95% CI 1.1-6.3; P = 0.04). CONCLUSIONS: Although in-vivo and in-vitro
      studies demonstrate induced hypothermia may be protective in TBI, our study
      demonstrates that admission hypothermia was associated with increased mortality
      in isolated, blunt, moderate to severe TBI. Further prospective research is
      needed to elucidate the role of thermoregulation in patients sustaining TBI.

PMID- 21872882
TI  - Neuroprotective effect of vaccination with autoantigen-pulsed dendritic cells
      after spinal cord injury.
AB  - BACKGROUND: Studies have shown that the development of a properly controlled
      autoreactive T cell response can serve as a therapeutic approach for spinal cord
      injury (SCI). Thus, vaccination with mature dendritic cells (DCs) pulsed with
      central nervous system (CNS) antigens that can prime autoreactive T cells have
      the potential for treating SCI. MATERIALS AND METHODS: Mature DCs pulsed with
      spinal cord homogenate (SCH), nonpulsed mature DC or phosphate-buffer solution
      (PBS) were injected into spinal cord-injured mice peritoneally. The functional
      recovery of spinal cord was measured by Basso mouse scale and footprint analysis.
      Spinal cord specimen was preserved for immunohistochemical staining to detect T
      cell infiltration, differentiation of neural stem/progenitor cells, and tissue
      preservation. RT-PCR and enzyme linked immunosorbent assay (ELISA) was used to
      detect the expression of cytokines and neurotrophic factors. RESULTS: Vaccination
      with DCs pulsed with SCH promoted pronounced functional recovery from SCI. The
      neuroprotection induced by SCH-pulsed DCs (SCH-DC) correlated to the accumulation
      of CD4(+) T cells in the lesion site. SCH-DC markedly affected the production of
      interferon-gamma, interleukin-12, and granulocyte-macrophage colony stimulating
      factor. SCH-DC also promoted expression of neurotrophic factors in the injured
      spinal cord and spleen cells. Furthermore, vaccination with SCH-DC enhanced
      neuronal differentiation of neural stem/progenitor cells, and it led to better
      tissue preservation. CONCLUSION: The results of the present study suggest that DC
      mediated immune regulation may be a potential therapeutic approach aimed at
      shifting the balance between immune and nerve cells in order to treat SCI.

PMID- 21872883
TI  - SP1 regulates the transcription of BMPR1A.
AB  - BACKGROUND: BMPR1A is a cell surface receptor in the bone morphogenetic protein
      (BMP) pathway. Mutations in BMPR1A predispose to juvenile polyposis (JP). Sp1 and
      related proteins are widely expressed regulators of gene transcription, including
      members of the BMP pathway. We set out to identify important transcription factor
      binding sites (TFBS) in the recently identified BMPR1A promoter and to assess for
      the role of Sp1 and associated proteins in its regulation. MATERIALS AND METHODS:
      The BMPR1A promoter was cloned into a luciferase reporter vector. Deletion
      fragments of this promoter insert were then constructed, of varying lengths and
      opposing directions, and were used to transfect HEK-293 and CRL-1459 cells. In
      silico analysis was performed to screen for relevant TFBS. Site-directed
      mutagenesis (SDM) was then employed to individually disrupt these TFBS in the
      wild-type (WT) vector. SDM constructs were then assessed for activity. RESULTS:
      Light activity from the deletion constructs ranged between 3% and 129% of the WT
      promoter. ModelInspector identified eight potential binding sites for Sp1- and
      Sp1-associated proteins that mapped to areas of marked loss or gain of activity
      from the deletion constructs. SDM of these TFBS led to a drop in activity in five
      mutants, which included 3 Sp1 sites, an ETSF site, and NFkappaB site.
      CONCLUSIONS: By combining in silico analysis and experimental data, Sp1 was found
      to be a candidate factor that likely plays a role in the transcriptional
      regulation of BMPR1A. This study potentially provides further insight toward the
      molecular basis of JP, and suggests that Sp1 plays a role in BMP signaling.

PMID- 21872884
TI  - Wound healing characteristics of ICAM-1 null mice devoid of all isoforms of ICAM
      1.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) permits leukocyte
      endothelial adhesion and transmigration during inflammation. Membrane-bound ICAM
      1 knockout mice have been used to understand this molecule's role in wound
      healing, but expressed spliced isoforms of ICAM-1 that may have impacted results.
      We aimed to characterize wound-healing in an ICAM-1 null model devoid of all ICAM
      1 isoforms. METHODS: Full-thickness 8-mm wounds were created on C57/BL6 wild-type
      (n = 24) and ICAM-1 null (n = 24) mice. Wound area was calculated using daily
      photographs. Histologic samples were harvested on postoperative Days 1, 3, 7, and
      14. Wound margins were evaluated for mRNA expression of 13 inflammatory
      cytokines. A separate group of wild-type and ICAM-1 null mice (n = 24) received
      full-thickness incisions with tensiometry measured at Day 14. Separately,
      complete blood counts were measured in unwounded wild-type (n = 4) and ICAM-1
      null mice (n = 4). RESULTS: Wound-closure was significantly delayed in ICAM-1
      null mice through Day 7 by gross and histologic measurement. mRNA expression of
      VEGF-A was increased in ICAM-1 null mice on Day 3, although no increase in VEGF-A
      was observed in the wound bed by immunohistochemistry. ICAM-1 null wounds
      demonstrated higher stiffness by tensiometry on Day 14 compared to the wild-type
      (1880 +/- 926 kPa versus 478 +/- 117 kPa; P < 0.01), and had higher counts of
      white blood cells (10,009 versus 5720 cells/MUL, P < 0.05), neutrophils (2130
      versus 630 cells/MUL, P < 0.01), and lymphocytes (7130 versus 4,740 cells/MUL, P
      < 0.05). CONCLUSIONS: ICAM-1 null mice demonstrate delayed wound-healing and
      decreased wound elasticity compared to wild-type controls. This lag, however, was
      less than observed in earlier membrane-bound ICAM-1 knockouts, suggesting that
      other ICAM-1 isoforms may promote delayed wound-healing.

PMID- 21872885
TI  - Role of high mobility group box 1 (HMGB1) in wound healing.
AB  - BACKGROUND: HMGB1, a non-histone chromosomal protein, can bind to the receptor
      for advanced glycation end products (RAGE) and act as an inflammatory mediator.
      We examined the role of HMGB1 in incisional wound healing and its possible
      mechanism of action through receptor for advanced glycation end products (RAGE).
      METHODS: Male Sprague-Dawley rats undergoing full-thickness incisional wounding
      with subcutaneous implantation of PVA sponges were given daily injections of
      ethyl pyruvate (EP) (40 mg/kg, i.p.), a potent inhibitor of HMGB1 release. At 7 d
      post-wounding, wound breaking strength, sponge collagen content, and wound fluid
      HMGB1 levels were assessed. In vitro rat dermal or wound-derived fibroblasts were
      cultured with recombinant HMGB1 or advanced glycation end product (AGE). Some
      cultures were co-treated with a RAGE-blocking antibody. Fibroblast proliferation
      and collagen synthesis were assayed. RESULTS: In vivo treatment with EP
      significantly decreased wound HMGB1 levels (P < 0.05), which was paralleled by
      increased wound breaking strength (P < 0.05) and wound collagen content (P <
      0.05). In vitro treatment with HMGB1 (100 ng/mL) had no effect on fibroblast
      proliferation but significantly reduced collagen synthesis (P < 0.05). This
      effect was abrogated by co-treatment with anti-RAGE antibody. Fibroblasts treated
      with AGE had lower collagen synthesis (P < 0.01), which was restored by anti-RAGE
      antibody treatment. CONCLUSION: HMGB1 impairs fibroblast collagen synthesis.
      Reducing wound HMGB1 levels lead to increased tensile strength and collagen
      synthesis. The data suggest that HMGB1 affects collagen synthesis through
      activation of RAGE.

PMID- 21872886
TI  - Colectomy performance improvement within NSQIP 2005-2008.
AB  - BACKGROUND: All open and laparoscopic colectomies submitted to the American
      College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)
      were evaluated for trends and improvements in operative outcomes. METHODS: 48,247
      adults (>=18 y old) underwent colectomy in ACS NSQIP, as grouped by surgical
      approach (laparoscopic versus open), urgency (emergent versus elective), and
      operative year (2005 to 2008). Primary outcomes measured morbidity, mortality,
      perioperative, and postoperative complications. RESULTS: The proportion of
      laparoscopic colectomies performed increased annually (26.3% to 34.0%), while
      open colectomies decreased (73.7% to 66.0%; P < 0.0001). Most emergent
      colectomies were open procedures (93.5%) representing 24.3% of all open cases.
      The overall risk-adjusted morbidity and mortality for all colectomy procedures
      did not show a statistically significant change over time, however, morbidity and
      mortality increased among open colectomies (r = 0.03) and decreased among
      laparoscopic colectomies (r = -0.04; P < 0.0001). Postoperative complications
      reduced significantly including superficial surgical site infections (9.17% to
      8.20%, P < 0.004), pneumonia (4.60% to 3.97%, P < 0.0001), and sepsis (4.72%,
      2005; 6.81%, 2006; 5.62%, 2007; 5.09%, 2008; P < 0.0002). Perioperative
      improvements included operative time (169.2 to 160.0 min), PRBC transfusions
      (0.27 to 0.25 units) and length of stay (10.5 to 6.61 d; P < 0.0001). CONCLUSION:
      It appears that laparoscopic colectomies are growing in popularity over open
      colectomies, but the need for emergent open procedures remains unchanged. Across
      all colectomies, however, key postoperative and perioperative complications have
      improved over time. Participation in ACS NSQIP demonstrates quality improvement
      and may encourage greater enrollment.

PMID- 21872888
TI  - Ethnicity and insurance status affect health disparities in patients with
      gallstone disease.
AB  - BACKGROUND: Complex gallstone disease is associated with greater risk of
      morbidity, associated with operative complications and longer hospital stays. The
      purpose of this study is to evaluate whether ethnicity or insurance status is
      associated with differences in presentation and outcomes in gallstone disease.
      MATERIALS AND METHODS: A retrospective analysis was performed for all patients
      who underwent cholecystectomy between August 1, 2007 and May 31, 2010 at the only
      teaching hospital in the region. Analysis of Variance, Chi square (chi(2)) and
      logistical regression analyses were used to evaluate the impact of ethnicity and
      insurance status on the complexity of gallstone disease and surgical outcomes.
      RESULTS: A total of 562 patients had a cholecystectomy during the study period,
      of whom 255 (45.4%) were Latino. Latino patients were significantly younger than
      any other ethnic group (P < 0.001) and had a significantly higher rate of being
      uninsured (40%, P = 0.03). Latino patients were significantly more likely to
      require ERCP (38.6% versus 28.8% for non-Latino, P = 0.01). Latino patients had a
      significantly higher white blood cell count (P = 0.017). There were no
      significant differences in liver function tests, bilirubin levels, albumin
      levels, hospital lengths of stay, operation types, pathology types, or
      complication rates between ethnic groups. Uninsured patients were significantly
      younger (P = 0.003) and were more likely to require an ERCP (39.5% versus 26.8%
      for privately insured and 31.9% for publicly insured, P = 0.04). Patients with no
      insurance were significantly more likely to have a higher white blood cell count
      (P = 0.039) and aspartate aminotransferase (AST) level (P = 0.04). Patients with
      public insurance and no insurance had a significantly longer median length of
      hospital stay (4.0 d versus 3.0 d for privately insured, P = 0.045). There were
      no significant differences in operation types, complication rates, or pathologic
      diagnosis based on insurance status. CONCLUSIONS: In our population, ethnicity
      and insurance status do play a role in the presentation and care of patients with
      gallstone disease. Latino and uninsured patients present with a higher complexity
      of disease and require interventions more frequently.

PMID- 21872887
TI  - A murine xenograft model of spontaneous metastases of human lung adenocarcinoma.
AB  - BACKGROUND: The flank is commonly used for primary xenografts in mice, but it is
      rare for these tumors to metastasize. Tail vein injection creates a pattern of
      metastases, but is artificial. We hypothesized that the liver is a convenient
      alternative xenograft site and that metastases would gradually proceed
      spontaneously. MATERIALS AND METHODS: Using 15 NOD.CB17-Prkdc(scid)/NcrCrl
      (NOD/SCID) mice, 10,000 A549 cells were xenografted into the liver while a second
      group of five mice were xenografted in the flank with 100,000 A549 cells as a
      control. Mice were euthanized and grossly dissected at 7 wk. A third group of
      seven mice received liver xenografts with A549 and a mouse each week was
      euthanized for 7 wk and evaluated. The liver, lung, and spleen were examined
      histologically. RESULTS: At 7 wk, 15/15 liver xenografted mice had gross primary
      tumor in the liver. Histologic review confirmed multiple microscopic foci of
      metastatic disease in all mice (15/15) throughout the lungs, mediastinal nodes,
      and spleen. The control group had primary tumor in the flank (4/5), but none had
      histologic evidence of metastases. Serially euthanized liver xenografted mice
      revealed evidence of a gradual spontaneous metastatic model system with the first
      histologic findings of micrometastases appearing in the lungs by wk 5, which
      became wide spread by wk 7. Splenic and mediastinal lymph node metastases
      developed in wk 6 and 7. CONCLUSIONS: Liver xenografting of A549 cells into
      NOD/SCID mice is a reliable way of developing widespread micrometastases. This
      model allows the study of a gradually developing solid tumor with subsequent
      metastatic spread.

PMID- 21872889
TI  - Dopamine dysregulation syndrome after deep brain stimulation of the subthalamic
      nucleus in Parkinson's disease.
AB  - Dopamine dysregulation syndrome is a complication of the dopaminergic treatment
      for Parkinson's disease, probably related to sensitization of the mesolimbic
      dopamine system. The relationship between dopamine dysregulation syndrome and
      deep brain stimulation of the subthalamic nucleus remains unclear. We report
      three patients with Parkinson's disease who developed de novo dopamine
      dysregulation syndrome after deep brain stimulation of the subthalamic nucleus.
      We hypothesized that the combined effect of dopaminergic replacement therapy and
      deep brain stimulation on the limbic territory of the subthalamic nucleus could
      have precipitated the dopamine dysregulation syndrome in these patients, by
      inducing hyperstimulation of the mesolimbic dopamine system. The outcome of
      postoperative dopamine dysregulation syndrome is poor despite deep brain
      stimulation adjustments, attempts to reduce the dose of dopaminergic drugs and
      the addition of quetiapine or antidepressants.

PMID- 21872890
TI  - Implications of dredging induced changes in sediment particle size composition
      for the structure and function of marine benthic macrofaunal communities.
AB  - A meta-analysis approach was used to assess the effect of dredging induced
      changes in sediment composition, under different conditions of natural physical
      disturbance, for the structure and function of marine benthic macrofaunal
      communities. Results showed the sensitivity of macrofaunal communities increased
      as both the proportion of gravel increased and the level of natural physical
      disturbance decreased. These findings may be explained by the close association
      of certain taxa with the gravel fraction, and the influence of natural physical
      disturbance which, as it increases, tends to restrict the colonisation by these
      species. We conclude that maintaining the gravel content of surface sediments
      after dredging and, where practicable, locating extraction sites in areas of
      higher natural disturbance will minimise the potential for long-term negative
      impacts on the macrofauna.

PMID- 21872891
TI  - State mandatory overtime regulations and newly licensed nurses' mandatory and
      voluntary overtime and total work hours.
AB  - Nurse overtime has been used to handle normal variations in patient census and to
      control chronic understaffing. By 2010, 16 states had regulations to limit nurse
      overtime. We examined mandatory overtime regulations and their association with
      mandatory and voluntary overtime and total hours worked by newly licensed
      registered nurses (NLRNs). For this secondary data analysis, we used a panel
      survey of NLRNs; the final dataset consisted of 1,706 NLRNs. Nurses working in
      states that instituted overtime regulations after 2003 or in states that
      restricted any type of mandatory overtime had a lower probability of experiencing
      mandatory overtime than those nurses working in states without regulations.
      Nurses who worked in states with mandatory overtime regulations reported fewer
      total hours worked per week. The findings of this study provided insight into how
      mandatory overtime regulations were related to nurse mandatory and voluntary
      overtime and the total number of hours worked. Future research should investigate
      institutions' compliance with regulations and the impact of regulations on nurse
      and patient outcomes.

PMID- 21872892
TI  - Variation in bulk tissue, fatty acid and monosaccharide delta13C values between
      autotrophic and heterotrophic plant organs.
AB  - The flowers of 23 species of grass and herb plants were collected from a
      mesotrophic grassland to assess natural variability in bulk, monosaccharide and
      fatty acid delta(13)C values from one plant community and were compared with
      previous analyses of leaves from the same species. The total mean bulk delta(13)C
      value of flower tissues was -28.10/00, and there was no significant difference
      between the mean delta(13)C(flower) values for grass (-27.80/00) and herb (
      28.20/00) species. On average bulk delta(13)C(flower) values were 1.10/00 higher
      than bulk delta(13)C(leaf) values, however, the delta(13)C(flower) and
      delta(13)C(leaf) values of grasses did not differ between organs suggesting that
      carbon isotope discrimination is different in grass and herb species. The
      abundance of different monosaccharides abundance varied between plant types, i.e.
      xylose concentrations in the grass flowers were as high as 40%, compared with up
      to 15% in the herb species, but the general relationship
      delta(13)C(arabinose)>delta(13)C(xylose)>delta(13)C(glucose)>delta(13)C(galactose
      which had been observed in leaves was similar in flowers (total mean delta(13)C
      values=-25.90/00, -27.20/00, -28.80/00 and -28.10/00, respectively). However, the
      average 5.40/00 depletion in the delta(13)C values of the C(16:0), C(18:2) and
      C(18:3) fatty acids in flowers compared to bulk tissue was significantly greater
      than observed for leaves. The trend C(16:0)<C(18:2)<C(18:3) previously observed
      in leaves was also observed in grass flowers (delta(13)C(C16:0)=-33.80/00;
      delta(13)C(C18:2)=-33.10/00; delta(13)C(C18:3)=-34.20/00) but not herb flowers
      (delta(13)C(C16:0)=-34.10/00; delta(13)C(C18:2)=-32.40/00; delta(13)C(C18:3)=
      34.50/00). We conclude: (i) that the biological processes influencing carbon
      isotope discrimination in grass flowers are different from herbs flowers; and,
      (ii) that a range of post-photosynthetic fractionation effects caused the
      observed differences between flower and leaf delta(13)C values, especially the
      significant (13)C-depletion in flower fatty acid delta(13)C values.

PMID- 21872893
TI  - alpha-Glucosidase inhibition and antihyperglycemic activity of prenylated
      xanthones from Garcinia mangostana.
AB  - An ethanol extract of the fruit case of Garcinia mangostan, whose most abundant
      chemical species are xanthones, showed potent alpha-glucosidase inhibitory
      activity (IC(50)=3.2 MUg/ml). A series of isolated xanthones (1-16) demonstrated
      modest to high inhibition of alpha-glucosidase with IC(50) values of 1.5-63.5
      MUM. In particular, one hitherto unknown xanthone 16 has a very rare 2-oxoethyl
      group on C-8. Kinetic enzymatic assays with a p-nitrophenyl glucopyranoside
      indicated that one of them, compound (9) exhibited the highest activity (K(i)=1.4
      MUM) and mixed inhibition. Using, a physiologically relevant substrate, maltose,
      as substrate, many compounds (6, 9, 14, and 15) also showed potent inhibition
      which ranged between 17.5 and 53.5 MUM and thus compared favorably with
      deoxynojirimycin (IC(50)=68.8 MUM). Finally, the actual pharmacological potential
      of the ethanol extract was demonstrated by showing that it could elicit reduction
      of postprandial blood glucose levels. Furthermore, the most active alpha
      glucosidase inhibitors (6, 9, and 14) were proven to be present in high
      quantities in the native seedcase by a HPLC chromatogram.

PMID- 21872894
TI  - Linderolides A-F, eudesmane-type sesquiterpene lactones and linderoline, a
      germacrane-type sesquiterpene from the roots of Lindera strychnifolia and their
      inhibitory activity on NO production in RAW 264.7 cells in vitro.
AB  - From the roots of Lindera strychnifolia, seven sesquiterpenes, named linderolides
      A-F and linderoline, were isolated together with six known compounds. The
      structures of linderolides A-F were elucidated to be eudesmane-type
      sesquiterpenes and linderoline was found to be a derivative of a germacrane-type
      sesquiterpene. Their structures were elucidated by means of spectroscopic
      evidence and that of linderolide A was confirmed by X-ray analysis. The
      inhibitory activity toward NO production was assayed using RAW264.7 cells with
      evaluating the cell growth by MTT method, linderolides C, D and F being found to
      be moderately active.

PMID- 21872895
TI  - Miscellaneous terpenoid constituents of Abies nephrolepis and their moderate
      cytotoxic activities.
AB  - Three monoterpenoids and two triterpenoids were isolated from Abies nephrolepis
      together with 53 known terpenoids. The structures of the compounds were
      established by 1D and 2D NMR spectroscopy. The absolute configuration of 3
      hydroxycamphane-2-carboxylic acid was established as (1S,2R,3S,4R) by Cu-Kalpha X
      ray crystallography. All 58 isolates were tested for cytotoxic activity against
      four tumor cells viz. A549 (human lung adenocarcinoma), Colo205 (colon
      adenocarcinoma), QGY-7703 (human hepatoma) and THP-1 (human monocytic leukemia).
      alpha-Cadinol exhibited the best effects on A549, Colo205 and QGY-7703 with
      IC(50) values of 8.6, 8.1 and 4.6 MUg/mL, respectively.

PMID- 21872896
TI  - Investigation of ultrasound screening efficiency for neural tube defects during
      pregnancy in rural areas of China.
AB  - OBJECTIVES: To understand the uptake and efficacy of ultrasound screening for
      neural tube defects (NTDs) during pregnancy, and the outcomes when NTDs were
      detected in rural areas of China. STUDY DESIGN: Prevalence study. METHODS: Four
      hundred and twenty-four women who delivered or gestated babies/fetuses with NTDs
      were selected at random in 20 counties of two provinces of China from March 2008
      to January 2009. The uptake of ultrasound screening, NTD detection rate and
      termination of pregnancy (TOP) rate were calculated and analyzed. Generalized
      estimating equations were employed to control for potential confounding factors.
      RESULTS: The uptake of ultrasound screening was 98.8%. Among the study subjects,
      361 (85.1%) NTDs were detected and 63 (14.9%) were not detected by prenatal
      ultrasound screening. The total detection rate was 43.3% (15.6%, 49.6% and 52.2%
      in the first, second and third trimesters, respectively; P < 0.05). Taking the
      possibility of NTD detection in the first trimester as 1.0, the possibilities in
      the second and third trimesters were 10.9 [95% confidence interval (CI) 6.5-18.3]
      and 25.2 (95% CI 13.3-47.6), respectively. The detection rate at the township
      health centres (THCs), family planning centres (FPCs), maternal and child care
      service centres (MCSCs) and hospitals was 24.5%, 29.1%, 53.6% and 78.1%,
      respectively (P < 0.05). Taking the possibility of NTD detection at THCs as 1.0,
      the possibilities at FPCs, MCSCs and hospitals were 0.9 (95% CI 0.5-1.6), 3.4
      (95% CI 1.9-6.1) and 2.1 (95% CI 1.3-3.4), respectively. Three hundred and fifty
      five (98.3%) of the 361 NTDs detected at prenatal ultrasound screening ended in
      TOP. CONCLUSIONS: The uptake of ultrasound screening was satisfactory, but the
      NTD detection rate was low. Ultrasound screening did not play its full role in
      the secondary prevention of NTDs in the study areas. Medical institutions in
      rural areas in China need to improve their ultrasound screening skills in order
      to increase the efficacy of NTD control.

PMID- 21872897
TI  - Ultrasonographic assessment of standing laparotomy wound healing in dairy cows.
AB  - The surgical wounds of 40 cows with a standing clean laparotomy were assessed 10
      15 days after surgery. The abdominal wall thickness on the upper (w1), the middle
      (w2) and the lower (w3) third of the wound (and the contralateral flank n1, n2,
      and n3), the presence of edema, cavitary lesion, capsulated lesion, or
      visualization of shadow artifact in the wound were assessed ultrasonographically.
      On day 30, wound healing status (normal or surgical site infection (SSI)) was
      determined. Five out of 39 cows (12.8%) had SSI. A significant positive
      correlation was found between w3 and edema (p<0.01; r=0.44), w3/n3 and edema
      (p<0.05; r=0.32), w3 and pain on wound palpation (p<0.01; r=0.41); w3/n3 and the
      presence of pain (p<0.002; r=0.49) and w2/n2 and pain when palpating the wound
      (p<0.05; r=0.33). No association was found between the ultrasonographic evidence
      of edema and SSI (p=0.10), cavitary lesion and SSI (p=0.65), encapsulated lesion
      and SSI (p=1), and shadow artefact and SSI (p=1). The wound ultrasonography 10-15
      days after surgery was not predictive of abnormal wound healing.

PMID- 21872899
TI  - Broadband terahertz ultrasonic transducer based on a laser-driven piezoelectric
      semiconductor superlattice.
AB  - Spectral characteristics of laser-generated acoustic waves in an InGaN/GaN
      superlattice structure are studied at room temperature. Acoustic vibrations in
      the structure are excited with a femtosecond laser pulse and detected via
      transmission of a delayed probe pulse. Seven acoustic modes of the superlattice
      are detected, with frequencies spanning a range from 0.36 to 2.5THz. Acoustic
      waves up to ~2THz in frequency are not significantly attenuated within the
      transducer which indicates excellent interface quality of the superlattice. The
      findings hold promise for broadband THz acoustic spectroscopy.

PMID- 21872898
TI  - Estimates of human immunodeficiency virus incidence among female sex workers in
      north central Nigeria: implications for HIV clinical trials.
AB  - We estimated the HIV incidence among commercial female sex workers (FSWs) in
      north central Nigeria using bimodal methodology. Using a cross-sectional study
      design, a total of 900 active FSWs between the ages of 18 and 35 years were
      recruited from 52 brothels within Nasarawa State, Nigeria. A rapid test algorithm
      was used to determine their HIV status. The BED IgG-Capture enzyme immunoassay
      (CEIA) was applied on the HIV-seropositive samples to detect recent HIV-1
      infection for the estimation of incidence among those with HIV infection. Of the
      900 FSWs tested, 335 (37.2%) were found to be positive for HIV. Of these, 63
      showed evidence of recent infection. Using two third-generation BED analysis
      approaches that account for false-recent rate, an annualized adjusted HIV
      incidence of 11.97% (95% CI: 8.51-15.43%) and 12.36% (95% CI: 8.18-16.34%) was
      observed; difference P>0.05. In addition, 875 (97.2%) of the FSWs readily agreed
      to participate in HIV clinical trials. We have developed the expertise and
      infrastructure necessary for clinical trial investigations in sub-Saharan Africa.
      We have recorded a high proportion of recent HIV infections among FSWs in Nigeria
      and also provided an enabling environment for future studies of HIV prevention
      methods.

PMID- 21872900
TI  - Partitioning of dissolved organic matter-bound mercury between a hydrophobic
      surface and polysulfide-rubber polymer.
AB  - This study investigated the role of dissolved organic matter on mercury
      partitioning between a hydrophobic surface (polyethylene, PE) and a reduced
      sulfur-rich surface (polysulfide rubber, PSR). Comparative sorption studies
      employed polyethylene and polyethylene coated with PSR for reactions with DOM
      bound mercuric ions. These studies revealed that PSR enhanced the Hg-DOM removal
      from water when DOM was Suwannee River natural organic matter (NOM), fulvic acid
      (FA), or humic acid (HA), while the same amount of 1,3-propanedithiol-bound
      mercuric ion was removed by both PE and PSR-PE. The differences for Hg-DOM
      removal efficiencies between PE and PSR-PE varied depending on which DOM was
      bound to mercuric ion as suggested by the PE/water and PSR-PE/water partition
      coefficients for mercury. The surface concentrations of mercury on PE and PSR-PE
      with the same DOM measured by x-ray photoelectron spectroscopy were similar,
      which indicated the comparable amounts of immobilized mercury on PE and PSR-PE
      being exposed to the aqueous phase. With these observations, two major pathways
      for the immobilization reactions between PSR-PE and Hg-DOM were examined: 1)
      adsorption of Hg-DOM on PE by hydrophobic interactions between DOM and PE, and 2)
      addition reaction of Hg-DOM onto PSR by a complexation reaction between Hg and
      PSR. The percent contribution of each pathway was derived from a mass balance and
      the ratios among aqueous mercury, PE-bound Hg-DOM, and PSR-bound Hg-DOM
      concentrations. The results indicate strong binding of mercuric ion with both
      dissolved organic matter and PSR polymer. The FT-IR examination of Hg-preloaded
      PSR-PEs after the reaction with DOM corroborated a strong interaction between
      mercuric ion and 1,3-propanedithiol compared to Hg-HA, Hg-FA, or Hg-NOM
      interactions.

PMID- 21872901
TI  - Protein kinase biochemistry and drug discovery.
AB  - Protein kinases are fascinating biological catalysts with a rapidly expanding
      knowledge base, a growing appreciation in cell regulatory control, and an
      ascendant role in successful therapeutic intervention. To better understand
      protein kinases, the molecular underpinnings of phosphoryl group transfer,
      protein phosphorylation, and inhibitor interactions are examined. This analysis
      begins with a survey of phosphate group and phosphoprotein properties which
      provide context to the evolutionary selection of phosphorylation as a central
      mechanism for biological regulation of most cellular processes. Next, the kinetic
      and catalytic mechanisms of protein kinases are examined with respect to model
      aqueous systems to define the elements of catalysis. A brief structural biology
      overview further delves into the molecular basis of catalysis and regulation of
      catalytic activity. Concomitant with a prominent role in normal physiology,
      protein kinases have important roles in the disease state. To facilitate
      effective kinase drug discovery, classic and emerging approaches for
      characterizing kinase inhibitors are evaluated including biochemical assay
      design, inhibitor mechanism of action analysis, and proper kinetic treatment of
      irreversible inhibitors. As the resulting protein kinase inhibitors can modulate
      intended and unintended targets, profiling methods are discussed which can
      illuminate a more complete range of an inhibitor's biological activities to
      enable more meaningful cellular studies and more effective clinical studies.
      Taken as a whole, a wealth of protein kinase biochemistry knowledge is available,
      yet it is clear that a substantial extent of our understanding in this field
      remains to be discovered which should yield many new opportunities for
      therapeutic intervention.

PMID- 21872902
TI  - Inactivation and degradation of Microcystis aeruginosa by UV-C irradiation.
AB  - In this study, the mechanisms and factors affecting the inactivation and
      degradation efficiency during UV-C irradiation of Microcystis aeruginosa, a
      harmful cyanobacteria strain, were investigated. Under different experimental
      conditions, the concentrations of three bioactivity materials, including protein,
      phycocyanin and chl-a, were measured, and fluorescence regional integration (FRI)
      was used to quantify the results of excitation emission matrix fluorescence
      spectroscopy. Furthermore, any alternation occurring in cell ultrastructure was
      determined using transmission electron microscopy. Results showed that UV-C could
      effectively damage the M.aeruginosa cells, most likely via a 3-step procedure,
      including impairment of photosynthesis system, decomposition of cytoplasmic
      inclusions, and cell cytoclasis. Comparison of FRI values and biochemical
      parameters in the presence of H(2)O(2) and HCO(3)(-) under the UV-C irradiation
      revealed the importance of photolysis and reactive oxygen species (ROS)-induced
      oxidation. UV-C/H(2)O(2) treatment was more efficient due to enhanced ROS
      generation, while adding HCO(3)(-) inhibited the ROS-induced oxidation, resulting
      in suppression on reaction. Humic acid and NO(3)(-), two common water solutes,
      somewhat inhibited the inactivation and degradation processes, due to the ROS
      scavenging and "inner filter" effect.

PMID- 21872903
TI  - Effects of biodegradation and sorption by humic acid on the estrogenicity of
      17beta-estradiol.
AB  - The removal of 17beta-estradiol (E2) by biodegradation and sorption onto humic
      acid (HA) was examined at various HA concentrations. Subsequently, estrogenicity
      associated with E2 removal was estimated using E-screen bioassay. Results showed
      that E2 biodegradation and its subsequent transformation to estrone (E1) were
      significantly reduced with increasing HA concentration. In addition, the presence
      of nutrients enhanced the biodegradation of E2. Overall, E2 biodegradation was
      the dominating contributor to its removal, which demonstrated a significantly
      negative correlation with E2 sorption at various HA concentrations. The sorption
      of E2 by HA was significantly enhanced with increasing HA concentration.
      Estrogenicity associated with residual E2 showed that there existed a significant
      difference among various HA concentrations, with the lowest value in the absence
      of HA. The findings suggest that the presence of HA and nutrients in natural
      waters should be considered in assessing estrogenicity of environmental samples
      due to complex sorption and biodegradation processes.

PMID- 21872904
TI  - Microbial community response to addition of polylactate compounds to stimulate
      hexavalent chromium reduction in groundwater.
AB  - To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the
      Department of Energy Hanford site, we conducted a series of microcosm experiments
      using a range of commercial electron donors with varying degrees of lactate
      polymerization (polylactate). These experiments were conducted using Hanford
      Formation sediments (coarse sand and gravel) immersed in Hanford groundwater,
      which were amended with Cr(VI) and several types of lactate-based electron donors
      (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the
      polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed
      that polylactate compounds stimulated an increase in bacterial biomass and
      activity to a greater extent than sodium lactate when applied at equivalent
      carbon concentrations. At the same time, concentrations of headspace hydrogen and
      methane increased and correlated with changes in the microbial community
      structure. Enrichment of Pseudomonas spp. occurred with all lactate additions,
      and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost
      complete sulfate reduction. The results of these experiments demonstrate that
      amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from
      solution most likely by both direct (enzymatic) and indirect (microbially
      generated reductant) mechanisms.

PMID- 21872905
TI  - Reduction of the movement and persistence of pesticides in soil through common
      agronomic practices.
AB  - Laboratory and field studies were conducted in order to determine the leaching
      potential of eight pesticides commonly used during pepper cultivation by use of
      disturbed soil columns and field lysimeters, respectively. Two soils with
      different organic matter content (soils A and B) were used. Additionally, soil B
      was amended with compost (sheep manure). The tested compounds were cypermethrin,
      chlorpyrifos-methyl, bifenthrin, chlorpyrifos, cyfluthrin, endosulfan, malathion
      and tolclofos-methyl. In soil B (lower organic matter content), only endosulfan
      sulphate, malathion and tolclofos-methyl were found in leachates. For the soil A
      (higher organic matter content) and amended soil B, pesticide residues were not
      found in the leachates. In addition, this paper reports on the use of common
      agronomic practices (solarization and biosolarization) to enhance degradation of
      these pesticides from polluted soil A. The results showed that both solarization
      and biosolarization enhanced the degradation rates of endosulfan, bifenthrin and
      tolclofos-methyl compared with the control. Most of the studied pesticides showed
      similar behavior under solarization and biosolarization conditions. However,
      chlorpyrifos was degraded to a greater extent in the solarization than in
      biosolarization treatment. The results obtained point to the interest in the use
      of organic amendment in reducing the pollution of groundwater by pesticide
      drainage and in the use of solarization and biosolarization in reducing the
      persistence of pesticides in soil.

PMID- 21872906
TI  - Microbial degradation of dissolved organic matter (DOM) and its influence on
      phenanthrene-DOM interactions.
AB  - Microbial degradation-induced changes in the characteristics of dissolved organic
      matter (DOM), and the subsequent effects on phenanthrene-DOM interactions were
      investigated based on the microbial incubation of DOM collected from four
      different sources for 28 d. Partially biodegraded DOM presented higher specific
      UV absorbance (SUVA), lower protein-like fluorescence, higher humic-like
      fluorescence, lower aliphatic carbon fraction, and higher hydrophobic neutral
      fractions compared to the original DOM. Microbial changes in DOM led to an
      increase in the isotherm nonlinearity as well as the extent of phenanthrene
      binding. A negative relationship between SUVA and the Freundlich n values was
      established for the original and the biodegraded DOM, suggesting that aromatic
      condensed structures may play important roles in providing nonlinear strong
      binding sites irrespective of microbial degradation. In contrast, there were two
      separate slopes of the correlations between the percentage of hydrophobic acid
      (HoA) fraction and the n values for the original and the biodegraded DOM with a
      higher slope exhibited for the latter, implying that the microbial utilization of
      oxygen-containing structures in the HoA fractions may contribute to enhancing the
      associated isotherm nonlinearity.

PMID- 21872907
TI  - Skeletal correlates of quadrupedalism and climbing in the anthropoid forelimb:
      implications for inferring locomotion in Miocene catarrhines.
AB  - Several well-known Miocene catarrhines, including Proconsul heseloni, have been
      inferred to combine quadrupedal walking in an arboreal substrate with a
      significant amount of climbing during locomotion. The degree to which some of
      these species were adapted to perform these behaviors is not fully understood due
      to the mosaic of 'ape-like' and 'monkey-like' traits identified in the forelimb.
      Given these unique combinations of forelimb features in the fossils, we report on
      forelimb traits that should be emphasized when investigating skeletal adaptation
      to quadrupedalism (defined in this manuscript as symmetrical gait movement on
      horizontal supports, excluding knuckle-walking) and climbing (including both
      vertical climbing and clambering). We investigate the correspondence between: 1)
      quadrupedalism and two well-known forelimb traits, humeral torsion and olecranon
      process length, and 2) climbing and phalangeal curvature. We also test the degree
      of phylogenetic signal in these relationships using phylogenetic generalized
      least-squares and branch length transformation methods in order to determine the
      models of best-fit. We present models that can be used to predict proportions of
      quadrupedalism and climbing in extant and extinct anthropoid taxa. Each trait
      behavior correlation is significant and characterized by an absence of
      phylogenetic signal. Thus, we employ models assuming a star phylogeny to predict
      locomotor proportions. The climbing model based on phalangeal curvature and a
      proxy for size provides the most accurate predictions of behavior across
      anthropoids. The two quadrupedalism models are less accurate, but distinguish
      highly quadrupedal species from those that are not. Predictive equations based on
      these traits support the inference that P. heseloni performed a high proportion
      of quadrupedalism with a significant climbing component. The degree of phalangeal
      curvature measured in Pliopithecus vindobonensis predicts that this Miocene
      catarrhine species performed a proportion of climbing similar to Proconsul, while
      humeral torsion and olecranon process length provide conflicting inferences of
      quadrupedal locomotion in this species.

PMID- 21872908
TI  - Comparison of the anticoagulant response of a novel fluorogenic anti-FXa assay
      with two commercial anti-FXa chromogenic assays.
AB  - INTRODUCTION: Fast and accurate monitoring is crucial in the successful
      regulation of coagulation therapy. For the treatment of venous thromboembolism,
      both unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) are
      commonly administered. The chromogenic anti-factor Xa (FXa) assay is currently
      considered the 'gold standard' assay for monitoring LMWH. However different
      commercial chromogenic methods often differ when tested with the same samples.
      Fluorogenic anti-FXa assays have the potential to offer greater benefits over
      chromogenic assays in terms of greater specificity, sensitivity and they are not
      so influenced by sample opacity or turbidity. MATERIALS AND METHODS: Commercial
      plasmas were spiked with pharmacologically relevant concentrations (0-1 U/ml) of
      UFH, enoxaparin, and tinzaparin. The fluorogenic assay was carried out using
      previously optimized concentrations of 12 nM FXa and 2.7MUM fluorogenic
      substrate, in addition to 6MUl of 100mM CaCl(2) and 44MUl of plasma. The
      Biophen(r) and Coamatic chromogenic assays were carried out according to the
      manufacturer's instructions. Reaction rates and endpoint values were analyzed and
      statistical analysis by means of one-way analysis of variance (ANOVA) was
      performed. RESULTS: The fluorogenic anti-FXa assay was found to have the broadest
      therapeutic range of 0-1 U/ml with CVs of<5% for UFH and tinzaparin and CVs<9%
      for enoxaparin. Despite their limited measuring range, good assay reproducibility
      was observed with both chromogenic kits. CONCLUSIONS: This study indicated that
      the fluorogenic assay is the most sensitive assay with the broadest dynamic range
      for monitoring LMWH therapy when compared with standard chromogenic assays.

PMID- 21872909
TI  - Imatinib mesylate (Gleevec) as protein-tyrosine kinase inhibitor elicits smooth
      muscle relaxation in isolated human prostatic tissue.
AB  - OBJECTIVE: To evaluate the mechanism of action of imatinib mesylate (Gleevec), a
      protein tyrosine kinase inhibitor on the human prostate with benign prostatic
      hyperplasia. METHODS: Prostate samples were obtained from 16 patients with benign
      prostatic hyperplasia (mean age 68.3 +/- 1.9 years), who had undergone
      transurethral prostatectomy. In tissue bath studies, cumulative concentration
      response curves were constructed for imatinib after precontraction with 120 mM
      KCl. Imatinib-induced relaxation was quantitated in tissues treated with l-N(G)
      Nitroarginine Methyl Ester (l-NAME) (an inhibitor of nitric oxide synthase) or 1H
      [1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylyl cyclase
      inhibitor). Two K+ channel blockers (adenosine triphosphate [K(ATP)] and Large
      conductance Ca(2+)-activated K(+) channels [BK(Ca2+)] channels) were also
      evaluated as antagonists of imatinib-induced relaxation and repeated in the
      presence of the alpha-adrenergic receptor blocker alfuzosin. An electrical field
      stimulation (1-20 Hz, 5 ms, 5 seconds, 60 V)-induced contractile response was
      performed on strips incubated with imatinib (10(-3) M). RESULTS: KCl-induced
      contractions in human prostatic tissue were significantly inhibited by imatinib
      (maximal response 84.9 +/- 4.5%) and were attenuated by l-NAME (42%, P < .001)
      and ODQ (43%, P < .001). This relaxant effect was also suppressed by
      glibenclamide (adenosine triphosphate-sensitive K+ channel blocker, 41%, P <
      .001) and tetraethylammonium (BK(Ca2+) channel blocker, 24%, P < .05).
      CONCLUSION: Imatinib induced prostatic smooth muscle relaxation in vitro. This
      effect was suppressed by l-NAME and ODQ, showing a dependence on the nitric oxide
      cyclic guanosine monophosphate pathway and modulated by the K(ATP) and BK(Ca2+)
      K+ channels. Our findings suggest that imatinib can augment relaxation of human
      prostatic tissues by way of a novel ligand-protein tyrosine kinase signaling
      pathway.

PMID- 21872910
TI  - Human bladder smooth muscle cell damage in disturbed oxygen tension.
AB  - OBJECTIVE: To characterize human bladder smooth muscle cell reactions to
      disturbed oxygen tension. Clinical studies have shown a close correlation between
      bladder ischemia and lower urinary tract symptoms in elderly patients. MATERIALS
      AND METHODS: Confluent cultured human bladder smooth muscle cells were incubated
      under normoxia, continuous hypoxia, and oxidative stress (hypoxia/reoxygenation)
      conditions using a computerized oxycycler system. After 48 hours, cell samples
      were collected and processed for fluorometric assessment of oxidative injury,
      enzyme immunoassay of antioxidant capacity, and transmission electron microscopy.
      RESULTS: Lipid peroxidation was found in cell hypoxia and oxidative stress,
      whereas protein oxidation was evident in oxidative stress only. Cell antioxidant
      capacity decreased in oxidative stress but remained unchanged in hypoxia.
      Oxidative products were present in cell oxidative stress only, whereas
      nitrosative products increased in both hypoxia and oxidative stress conditions.
      Forty-eight hours of hypoxia and oxidative stress had no effect on cell
      senescence. Thickened deformed cell membrane, swollen mitochondria, and enlarged
      endoplasmic reticulum (ER) were found in cell hypoxia. Partially lost cell
      membrane with increased caveolae, swollen mitochondria with degraded cristae,
      splintered ER, and increased lysosomes were evident in cell oxidative stress.
      CONCLUSION: Human bladder smooth muscle cells are highly reactive to
      nonconforming oxygen tension. Reactions to hypoxia are consistent with cell
      survival signaling to cope with lack of oxygen. Changes in oxidative stress
      indicate extensive damage and deterioration of the subcellular elements. Hypoxic
      and oxidative damage may be an important mechanism of smooth muscle degeneration
      in bladder conditions with disturbed oxygen tension.

PMID- 21872911
TI  - Radical hysterectomy: a comparison of surgical approaches after adoption of
      robotic surgery in gynecologic oncology.
AB  - OBJECTIVE: To compare intra-operative, postoperative and pathologic outcomes of
      three surgical approaches to radical hysterectomy and bilateral pelvic lymph node
      dissection over a three year time period during which all three approaches were
      used. METHODS: We reviewed all patients who underwent radical hysterectomy with
      pelvic lymph node dissection between 1/2007 and 11/2010. Comparison was made
      between robotic, laparoscopic and open procedures in regard to surgical times,
      complication rates, and pathologic findings. RESULTS: A total of 95 radical
      hysterectomy procedures were performed during the study period: 30 open (RAH), 31
      laparoscopic (LRH) and 34 robotic (RRH). There were no differences in age, body
      mass index or other demographic factors between the groups. Operative time was
      significantly shorter in the RAH compared to LRH and RRH (265 vs 338 vs 328min,
      p=0.002). Estimated blood loss was significantly lower in LRH and RRH compared
      with RAH (100 vs 100 vs 350mL, p<0.001). Thirteen (24%) of RAH required blood
      transfusion. Conversion rates were higher in the LRH (16%) compared to RRH (3%)
      although not significant (p=0.10). Median length of stay was significantly
      shorter in RRH (1day) vs LRH or RAH (2 vs 4days, p<0.01). Pathologic findings
      were similar among all groups. CONCLUSION: Minimally invasive surgery has made a
      significant impact on patients undergoing radical hysterectomy including decrease
      in blood loss and transfusion rates however; operative times were significantly
      longer compared to open radical hysterectomy. Our findings suggest that the
      robotic approach may have the added benefit of even shorter length of stay
      compared to traditional laparoscopy.

PMID- 21872912
TI  - Functional KCa3.1 K+ channels are required for human fibrocyte migration.
AB  - BACKGROUND: Fibrocytes are bone marrow-derived CD34(+) collagen I-positive cells
      present in peripheral blood that develop alpha-smooth muscle actin expression and
      contractile activity in tissue culture. They are implicated in the pathogenesis
      of tissue remodeling and fibrosis in both patients with asthma and those with
      idiopathic pulmonary fibrosis. Targeting fibrocyte migration might therefore
      offer a new approach for the treatment of these diseases. Ion channels play key
      roles in cell function, but the ion-channel repertoire of human fibrocytes is
      unknown. OBJECTIVE: We sought to examine whether human fibrocytes express the
      K(Ca)3.1 K(+) channel and to determine its role in cell differentiation,
      survival, and migration. METHODS: Fibrocytes were cultured from the peripheral
      blood of healthy subjects and patients with asthma. Whole-cell patch-clamp
      electrophysiology was used for the measurement of ion currents, whereas mRNA and
      protein were examined to confirm channel expression. Fibrocyte migration and
      proliferation assays were performed in the presence of K(Ca)3.1 ion-channel
      blockers. RESULTS: Human fibrocytes cultured from the peripheral blood of both
      healthy control subjects and asthmatic patients expressed robust K(Ca)3.1 ion
      currents together with K(Ca)3.1 mRNA and protein. Two specific and distinct
      K(Ca)3.1 blockers (TRAM-34 and ICA-17043) markedly inhibited fibrocyte migration
      in transwell migration assays. Channel blockers had no effect on fibrocyte
      growth, apoptosis, or differentiation in cell culture. CONCLUSIONS: The K(+)
      channel K(Ca)3.1 plays a key role in human fibrocyte migration. Currently
      available K(Ca)3.1-channel blockers might therefore attenuate tissue fibrosis and
      remodeling in patients with diseases such as idiopathic pulmonary fibrosis and
      asthma through the inhibition of fibrocyte recruitment.

PMID- 21872913
TI  - Prediction of IgE-binding epitopes by means of allergen surface comparison and
      correlation to cross-reactivity.
AB  - BACKGROUND: The experimental determination of conformational allergen epitopes
      recognized by IgE is a difficult task because they often involve discontinuous
      amino acid residues, being separated in the primary allergen sequence, and
      require the correct allergen fold. OBJECTIVE: We sought to develop a
      computational tool for the localization of conformational IgE epitopes by using a
      structure-based comparison of allergen surfaces and IgE cross-reactivity data.
      METHODS: Our approach involves the quantitative analysis of geometric and
      physicochemical surface parameters and the subsequent correlation of surface
      similarity scores to immunologic data. The software tool Surface comparison-based
      Prediction of Allergenic Discontinuous Epitopes (SPADE) is able to predict the
      IgE epitopes of an allergen given the availability of at least 2 structural
      models and IgE reactivity data. RESULTS: We report on the application of our tool
      to 3 allergen families: the lipocalins, the group 10 pathogenesis-related
      proteins, and the group 2/3 grass pollen allergens. First, we succeeded in the
      partial relocalization of IgE epitopes of bovine beta-lactoglobulin and grass
      pollen Phl p 2 as known from the x-ray structures of their antibody complexes.
      Second, we measured the relative binding of anti-Bet v 1 IgE to 10 homologous
      proteins and correlated these data to surface comparison results involving Bet v
      1, 5 of the homologs, and 2 hypoallergenic Bet v 1 isoforms. Thereby we predicted
      IgE-reactive surface portions in agreement with IgE epitope-mapping studies.
      CONCLUSION: Our approach is the first for the prediction of IgE epitopes by
      combining structural and IgE cross-reactivity data. It should be useful for the
      development of point-mutated or structurally disrupted allergen derivatives for
      allergen-specific immunotherapy.

PMID- 21872914
TI  - Plasma metalloproteinase levels are dysregulated in signal transducer and
      activator of transcription 3 mutated hyper-IgE syndrome.

PMID- 21872915
TI  - Mode and place of delivery, gastrointestinal microbiota, and their influence on
      asthma and atopy.
AB  - BACKGROUND: Both gastrointestinal microbiota composition and cesarean section
      have been linked to atopic manifestations. However, results are inconsistent, and
      the hypothesized intermediate role of the microbiota in the association between
      birth mode and atopic manifestations has not been studied yet. OBJECTIVES: We
      sought to investigate the relationship between microbiota composition, mode and
      place of delivery, and atopic manifestations. METHODS: The Child, Parent and
      Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on
      birth characteristics, lifestyle factors, and atopic manifestations collected
      through repeated questionnaires from birth until age 7 years. Fecal samples were
      collected at age 1 month (n = 1176) to determine microbiota composition, and
      blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n =
      384) years to determine specific IgE levels. RESULTS: Colonization by Clostridium
      difficile at age 1 month was associated with wheeze and eczema throughout the
      first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home
      delivery compared with vaginal hospital delivery was associated with a decreased
      risk of eczema, sensitization to food allergens, and asthma. After stratification
      for parental history of atopy, the decreased risk of sensitization to food
      allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted
      odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only
      found for children with atopic parents. Mediation analysis showed that the
      effects of mode and place of delivery on atopic outcomes were mediated by C
      difficile colonization. CONCLUSION: Mode and place of delivery affect the
      gastrointestinal microbiota composition, which subsequently influences the risk
      of atopic manifestations.

PMID- 21872916
TI  - Atypical presentation of Churg-Strauss syndrome or an undescribed
      hypereosinophilic disease?

PMID- 21872917
TI  - Salivary cortisol levels and allergy in children: the ALADDIN birth cohort.
AB  - BACKGROUND: Pre- and postnatal stress have been related to allergy in children,
      but evidence from prospective studies is limited. Several environmental factors
      can influence the salivary cortisol level, which is used as a measure of activity
      of the hypothalamic-pituitary-adrenal axis. OBJECTIVE: The aim of this study was
      to assess the association between salivary cortisol levels at 6 months of age and
      allergic manifestations during the first 2 years of life. METHODS: Salivary
      samples for the analysis of cortisol level were collected at 6 months of age on 3
      occasions during 1 day from 203 children. Blood samples were collected at 6, 12,
      and 24 months of age for analyses of specific IgE. Information on allergy-related
      symptoms was obtained by repeated examinations of the children. Generalized
      estimating equation statistics were used to calculate the overall risk for
      outcome measures. RESULTS: The adjusted odds ratio for the relationship between
      morning cortisol level and IgE sensitization was 1.60 (95% CI, 1.22-2.10, P =
      .001) and for eczema it was 1.28 (95% CI, 1.03-1.59, P = .026). The odds ratio
      for afternoon cortisol level in relation to sensitization and eczema was 1.56
      (95% CI, 1.26-1.94, P < .001) and 1.33 (95% CI, 1.12-1.58, P = .001),
      respectively, and for evening cortisol level it was 1.49 (95% CI, 1.22-1.83, P <
      .001) and 1.37 (95% CI, 1.18-1.59, P < .001). Salivary cortisol level in the
      evening was associated with food allergy. CONCLUSION: The association between
      salivary cortisol levels in infancy and allergic sensitization and allergic
      symptoms suggests a role of an altered hypothalamic-pituitary-adrenal axis in the
      etiological process of allergies.

PMID- 21872918
TI  - Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR
      CABG): a randomised controlled superiority trial.
AB  - BACKGROUND: Comparative assessment of clinical outcomes after use of drug-eluting
      stents versus bare-metal stents for treatment of aortocoronary saphenous vein
      graft lesions has not been undertaken in large randomised trials. We aimed to
      undertake a comparison in a randomised trial powered for clinical endpoints.
      METHODS: In this randomised superiority trial, patients with de-novo saphenous
      vein graft lesions were assigned by computer-generated sequence (1:1:1:3) to
      receive either drug-eluting stents (one of three types: permanent-polymer
      paclitaxel-eluting stents, permanent-polymer sirolimus-eluting stents, or
      biodegradable-polymer sirolimus-eluting stents) or bare-metal stents.
      Randomisation took place immediately after crossing of the lesion with a
      guidewire, and was stratified for each participating centre. Investigators
      assessing data were masked to treatment allocation; patients were not masked to
      allocation. The primary endpoint was the combined incidence of death, myocardial
      infarction, and target lesion revascularisation at 1 year. Analysis was by
      intention to treat. This trial is registered at ClinicalTrials.gov, number
      NCT00611910. FINDINGS: 610 patients were allocated to treatment groups (303 drug
      eluting stent, 307 bare-metal stent). Drug-eluting stents reduced the incidence
      of the primary endpoint compared with bare-metal stents (44 [15%] vs 66 [22%]
      patients; hazard ratio [HR] 0.64, 95% CI 0.44-0.94; p=0.02). Target lesion
      revascularisation rate was reduced by drug-eluting stents (19 [7%] vs 37 [13%]
      patients; HR 0.49, 95% CI 0.28-0.86; p=0.01). No significant differences were
      seen between drug-eluting stents and bare-metal stents regarding all-cause
      mortality (15 [5%] vs 14 [5%] patients; HR 1.08, 95% CI 0.52-2.24; p=0.83),
      myocardial infarction (12 [4%] vs 18 [6%]; HR 0.66, 95% CI 0.32-1.37; p=0.27), or
      definite or probable stent thrombosis (2 [1%] in both groups; HR 1.00, 95% CI
      0.14-7.10; p=0.99). INTERPRETATION: In patients undergoing percutaneous coronary
      intervention for de-novo saphenous vein graft lesions, drug-eluting stents are
      the preferred treatment option because they reduce the risk of adverse events
      compared with bare-metal stents. FUNDING: Deutsches Herzzentrum.

PMID- 21872919
TI  - Secondary prevention of heart disease and stroke: work to do.

PMID- 21872921
TI  - Stents and failing vein grafts: are we any wiser after ISAR?

PMID- 21872922
TI  - Expanding the ecotoxicological toolbox: the inclusion of polychaete reproductive
      endpoints.
AB  - In the last 15 years the diversity of pollutants and routes of impact have
      increased. However, the polychaete families, species and endpoints investigated
      have remained fairly constant. Reproductive outputs are more ecologically
      relevant than adult physiological or biochemical changes. Nevertheless, there
      remains a paucity of data on the reproductive responses of the popular species to
      pollutants which limits our ability to understand the true ecological impacts of
      such contaminants on natural populations. We highlight the current knowledge gaps
      in our understanding of the impacts of pollutants on the 'model' species'
      reproductive biology and therefore the potential ecological impacts of such
      contaminants on their natural populations, and the potential benefits of a wider
      use of polychaete reproductive endpoints for ecotoxicological assessments. The
      following priority areas are suggested for inclusion in the polychaete
      ecotoxicology toolbox: 1. Include reproductive endpoints as assessments of
      ecotoxicology for the traditional 'model' species and those that have different
      reproductive traits to ensure broad ecological relevance. 2. Nereids and
      Arenicola marina should be used to investigate the interaction of pollutants with
      the endocrine/environmental control of reproduction. 3. Polychaetes are ideal for
      addressing the under representation of male eco-toxicity effects. 4. Emerging
      pollutants should be assessed with reproductive endpoints together with the
      traditional biomarkers. 5. Effects of pollutants on larval behaviour need to be
      explored considering the limited but equivocal results so far.

PMID- 21872923
TI  - The performance of primary human renal cells in hollow fiber bioreactors for
      bioartificial kidneys.
AB  - Bioartificial kidneys (BAKs) containing human primary renal proximal tubule cells
      (HPTCs) have been applied in clinical trials. The results were encouraging, but
      also showed that more research is required. Animal cells or cell lines are not
      suitable for clinical applications, but have been mainly used in studies on BAK
      development as large numbers of such cells could be easily obtained. It is
      difficult to predict HPTC performance based on data obtained with other cell
      types. To enable more extensive studies on HPTCs, we have developed a bioreactor
      containing single hollow fiber membranes that requires relatively small amounts
      of cells. Special hollow fiber membranes with the skin layer on the outer surface
      and consisting of polyethersulfone/polyvinylpyrrolidone were developed. The
      results suggested that such hollow fiber membranes were more suitable for the
      bioreactor unit of BAKs than membranes with an inner skin layer. An HPTC
      compatible double coating was applied to the insides of the hollow fiber
      membranes, which sustained the formation of functional epithelia under bioreactor
      conditions. Nevertheless, the state of differentiation of the primary human cells
      remained a critical issue and should be further addressed. The bioreactor system
      described here will facilitate further studies on the relevant human cell type.

PMID- 21872924
TI  - Superhigh-magnetization nanocarrier as a doxorubicin delivery platform for
      magnetic targeting therapy.
AB  - The aim of this study describes the creation of superhigh-magnetization
      nanocarriers (SHMNCs) comprised of a magnetic Fe(3)O(4) (SHMNPs) core and a shell
      of aqueous stable self-doped poly[N-(1-one-butyric acid)]aniline (SPAnH), which
      have a high drug loading capacity (~27.1 wt%) of doxorubicin (DOX). The SHMNCs
      display superparamagnetic property with a magnetization of 89.7 emu/g greater
      than that of Resovist (a commercial contrast agent used for magnetic resonance
      imaging; 73.7 emu/g). Conjugating the anticancer drug DOX to these nanocarriers
      enhances the drug's thermal stability and maximizes the efficiency with which it
      is delivered by magnetic targeting (MT) therapy to MGH-U1 bladder cancer cells,
      in part by avoiding the effects of p-glycoprotein (P-gp) pumps to enhance the
      intracellular concentration of DOX. The high R2 relaxivity (434.7 mM(-1)s(-1)) of
      SHMNCs not only be a most effective MT carrier of chemotherapeutic agent but be
      an excellent contrast agent of MRI, allowing the assessment of the distribution
      and concentration of DOX in various tissues and organs. This advanced drug
      delivery system promises to provide more effective MT therapy and tumor treatment
      using lower therapeutic doses and potentially reducing the side effects of
      cardiotoxicity caused by DOX.

PMID- 21872925
TI  - The enhanced performance of bone allografts using osteogenic-differentiated
      adipose-derived mesenchymal stem cells.
AB  - Adipose tissue was only recently considered as a potential source of mesenchymal
      stem cells (MSCs) for bone tissue engineering. To improve the osteogenicity of
      acellular bone allografts, adipose MSCs (AMSCs) and bone marrow MSCs (BM-MSCs) at
      nondifferentiated and osteogenic-differentiated stages were investigated in vitro
      and in vivo. In vitro experiments demonstrated a superiority of AMSCs for
      proliferation (6.1+/-2.3 days vs. 9.0+/-1.9 days between each passage for BM
      MSCs, respectively, P<0.001). A significantly higher T-cell depletion (revealed
      by mixed lymphocyte reaction, [MLR]) was found for AMSCs (vs. BM-MSCs) at both
      non- and differentiated stages. Although nondifferentiated AMSCs secreted a
      higher amount of vascular endothelial growth factor [VEGF] in vitro (between 24
      and 72 h of incubation at 0.1-21% O(2)) than BM-MSCs (P<0.001), the osteogenic
      differentiation induced a significantly higher VEGF release by BM-MSCs at each
      condition (P<0.001). After implantation in the paraspinal muscles of nude rats, a
      significantly higher angiogenesis (histomorphometry for vessel development
      (P<0.005) and VEGF expression (P<0.001)) and osteogenesis (as revealed by
      osteocalcin expression (P<0.001) and micro-CT imagery for newly formed bone
      tissue (P<0.05)) were found for osteogenic-differentiated AMSCs in comparison to
      BM-MSCs after 30 days of implantation. Osteogenic-differentiated AMSCs are the
      best candidate to improve the angio-/osteogenicity of decellularized bone
      allografts.

PMID- 21872920
TI  - Use of secondary prevention drugs for cardiovascular disease in the community in
      high-income, middle-income, and low-income countries (the PURE Study): a
      prospective epidemiological survey.
AB  - BACKGROUND: Although most cardiovascular disease occurs in low-income and middle
      income countries, little is known about the use of effective secondary prevention
      medications in these communities. We aimed to assess use of proven effective
      secondary preventive drugs (antiplatelet drugs, beta blockers, angiotensin
      converting-enzyme [ACE] inhibitors or angiotensin-receptor blockers [ARBs], and
      statins) in individuals with a history of coronary heart disease or stroke.
      METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we
      recruited individuals aged 35-70 years from rural and urban communities in
      countries at various stages of economic development. We assessed rates of
      previous cardiovascular disease (coronary heart disease or stroke) and use of
      proven effective secondary preventive drugs and blood-pressure-lowering drugs
      with standardised questionnaires, which were completed by telephone interviews,
      household visits, or on patient's presentation to clinics. We report estimates of
      drug use at national, community, and individual levels. FINDINGS: We enrolled
      153,996 adults from 628 urban and rural communities in countries with incomes
      classified as high (three countries), upper-middle (seven), lower-middle (three),
      or low (four) between January, 2003, and December, 2009. 5650 participants had a
      self-reported coronary heart disease event (median 5.0 years previously [IQR 2.0
      10.0]) and 2292 had stroke (4.0 years previously [2.0-8.0]). Overall, few
      individuals with cardiovascular disease took antiplatelet drugs (25.3%), beta
      blockers (17.4%), ACE inhibitors or ARBs (19.5%), or statins (14.6%). Use was
      highest in high-income countries (antiplatelet drugs 62.0%, beta blockers 40.0%,
      ACE inhibitors or ARBs 49.8%, and statins 66.5%), lowest in low-income countries
      (8.8%, 9.7%, 5.2%, and 3.3%, respectively), and decreased in line with reduction
      of country economic status (p(trend)<0.0001 for every drug type). Fewest patients
      received no drugs in high-income countries (11.2%), compared with 45.1% in upper
      middle-income countries, 69.3% in lower middle-income countries, and 80.2% in low
      income countries. Drug use was higher in urban than rural areas (antiplatelet
      drugs 28.7% urban vs 21.3% rural, beta blockers 23.5%vs 15.6%, ACE inhibitors or
      ARBs 22.8%vs 15.5%, and statins 19.9%vs 11.6%; all p<0.0001), with greatest
      variation in poorest countries (p(interaction)<0.0001 for urban vs rural
      differences by country economic status). Country-level factors (eg, economic
      status) affected rates of drug use more than did individual-level factors (eg,
      age, sex, education, smoking status, body-mass index, and hypertension and
      diabetes statuses). INTERPRETATION: Because use of secondary prevention
      medications is low worldwide-especially in low-income countries and rural areas
      systematic approaches are needed to improve the long-term use of basic,
      inexpensive, and effective drugs. FUNDING: Full funding sources listed at end of
      paper (see Acknowledgments).

PMID- 21872926
TI  - The effect of coelomic fluid on the production of cytokines by the first
      trimester human placenta.
AB  - OBJECTIVE: To investigate the modulatory effects of coelomic fluid (CF) on the
      production of tumour necrosis factor-alpha (TNFalpha) and its receptors, TNF-R1
      and TNF-R2, interferon gamma (IFNgamma) and interleukin (IL)-10 by placental
      villous explants cultured under physiological oxygen (O(2)) concentration. STUDY
      DESIGN: In vitro culture of placental villous explants at atmospheric and
      physiological (6%) O(2) levels at varying concentrations of CF. MAIN OUTCOME
      MEASURES: Concentration of TNFalpha, TNF-R1, TNF-R2, IFNgamma and IL-10 in
      culture medium and villous explant homogenates, measured using flowcytometric
      bead arrays. RESULTS: The median level and interquartile range of cytokines and
      receptors present in CF were: TNFalpha 0.9 pg/ml (0.85, 0.95); IFNgamma 5.38
      pg/ml (4.96, 6.18); IL-10 1.59 pg/ml (1.45, 1.76); TNF-R1 6043.65 pg/ml (5961.39,
      6187.35) and TNF-R2 3563.52 pg/ml (3390.26, 3635.19). The PO(2) of CF was 48.74
      mmHg (SEM 1.59), equivalent to 6% O(2). Increasing doses of CF significantly (p <
      0.05) increased the levels of TNFalpha, TNF-R1 and TNF-R2 in the culture medium
      at both O(2) concentrations. TNF-R1 levels measured in placental homogenate
      increased up to 2-fold at both O(2) concentrations, but were significantly lower
      (1.96 fold; p = 0.03) at 6% O(2) compared to 20% O(2). CONCLUSIONS: The
      exocoelomic cavity in humans contains high levels of both soluble TNF-R1 and TNF
      R2. The addition of CF to placental tissue explants in culture modulates the
      placental secretion of TNFalpha-receptors and TNFalpha at both physiological and
      atmospheric O(2) tension resulting in a concentration much higher than that found
      in the CF. This may contribute to the maternal inflammatory response previously
      reported in normal early pregnancy.

PMID- 21872928
TI  - Response of soil bacterial community to repeated applications of carbendazim.
AB  - The effect of repeated carbendazim applications on functional diversity of
      culturable microorganisms and bacterial community composition was studied under
      field conditions. The functional diversity of soil culturable microbial community
      (Shannon index, H') reduced significantly (P<0.05) after the first introduction
      of carbendazim at levels of 0.94, 1.88 and 4.70 kg active ingredient (a.i.)ha(-1)
      and then recovered to that in the control with subsequent applications. An
      evident (P<0.01) difference in the bacterial community composition was observed
      after the second carbendazim application by Temperature Gradient Gel
      Electrophoresis (TGGE) analysis of 16S rRNA genes amplified from treated and
      control soils, which remained after the third and fourth treatments. Our results
      indicated that repeated carbendazim applications have a transient harmful effect
      on functional diversity of soil culturable microbial community and result in an
      alteration in bacterial community composition largely due to one species within
      the gamma-proteobacterium.

PMID- 21872927
TI  - The morphometry of materno-fetal oxygen exchange barrier in a baboon model of
      obesity.
AB  - INTRODUCTION: More than one-fourth of U.S. women are overweight; more than one
      third are obese. Maternal obesity has been linked to an increased incidence of
      stillbirths, fetal macrosomia, fetal intrauterine growth restriction and pre
      eclampsia. The placenta plays a key role in the nutrients and oxygen supply to
      the fetus. The data about structural changes in the placental villous membrane
      (VM), a major component of the feto-maternal nutrient and oxygen exchange
      barrier, during obesity are sparse and inconsistent. Our objective was to
      evaluate the morphometric changes in the placental exchange barrier in a baboon
      model of obesity. MATERIALS AND METHODS: The previously described baboon model of
      maternal obesity was studied. We compared 4 obese to 4 non-obese baboons.
      Placental stereology with the use of transmission electron microscopy was
      performed to estimate VM oxygen diffusing capacities and morphometry. RESULTS:
      The specific placental oxygen diffusing capacities per unit of fetal weight were
      similar in baboons and humans. Maternal leptin concentrations correlated
      negatively with placental basement membrane thickness (r = -0.78, p < 0.05),
      while fetal leptin levels correlated negatively with endothelial thickness of
      fetal capillaries (r = -0.78, p < 0.05). The total and specific villous membrane
      oxygen diffusing capacities were not different between the two groups.
      CONCLUSION: To the best of our knowledge this is the first report of placental
      oxygen diffusing capacities and placental ultrastructural changes in a baboon
      model of obesity. Previously reported placental inflammation in maternal obesity
      is not associated with changes in the VM diffusing capacities and ultrastructure.

PMID- 21872929
TI  - High prevalence of Hepatitis E virus in French domestic pigs.
AB  - The importance of the domestic pig reservoir for Hepatitis E virus (HEV) was
      assessed by estimating the seroprevalence and prevalence of HEV contaminated
      livers in French slaughter-aged pigs. 6565 sera and 3715 livers were randomly
      sampled from 186 pig farms throughout the country. Taking the sampling design
      into account, the farm-level seroprevalence was 65% (95% CI 57-74) and 31% (95%
      CI 24-38) of the slaughter-aged pigs had antibodies against HEV. The individual
      prevalence of HEV RNA positive livers was 4% (95% CI 2-6) and 24% (95% CI 17-31)
      of the farms had at least 1 positive liver. Most isolates were of genotype 3f
      (76.7%) with smaller amounts of 3c (18.6%) and 3e (4.6%). The high prevalence of
      HEV in pigs and the similarities between HEV subtypes from pigs and humans
      corroborates the possible zoonotic origin of some HEV autochthonous infections.

PMID- 21872930
TI  - Impact of ezetimibe coadministered with statins on cardiovascular events
      following acute coronary syndrome: a 3-year population-based retrospective cohort
      study in Taiwan.
AB  - BACKGROUND: Conflicting results using the combination of ezetimibe and statins to
      reduce the risk of cardiovascular events in patients with acute coronary syndrome
      (ACS) have been reported. OBJECTIVE: The aim of this work was to assess the
      effectiveness of ezetimibe coadministered with statins in reducing cardiovascular
      events in patients with ACS. METHODS: A retrospective cohort study of patients
      discharged after hospitalization with ACS was conducted from January 1, 2006, to
      December 31, 2007, and included those who were prescribed statins alone (n =
      37,753) and those who received ezetimibe plus statins (n = 1001) within 365 days
      after the hospitalization, based on patient data obtained from the National
      Health Insurance Research Database (NHIRD) in Taiwan. The propensity score method
      was used to identify a 1:1 matched cohort (n = 2002). Risk of rehospitalization
      for ACS was analyzed by a multivariable Cox proportional hazards regression
      model. RESULTS: The crude event rate of rehospitalization due to ACS in the
      original cohort was 13.4 per 100 person-years (268 events) in the combination
      group and 22.6 per 100 person-years (12,724 events) in the statins-alone group
      (adjusted hazard ratio [HR] 0.69; 95% CI, 0.62-0.78). The crude event rates of
      rehospitalization due to ACS in the matched cohort were 13.4 and 20.0 per 100
      person-years in the combination group and statins-alone group, respectively (HR
      0.62; 95% CI, 0.53-0.73). Compared with statins alone, the adjusted HRs for
      rehospitalization for percutaneous transluminal coronary angioplasty without
      stent, with stent, and revascularization for the combination group in the matched
      cohort were 0.61 (0.50-0.75), 0.62 (0.48-0.81), and 0.62 (0.51-0.76),
      respectively. CONCLUSIONS: Based on the data of Taiwan's NHIRD, our findings
      suggest that patients with ACS on ezetimibe combined with statins had a
      significantly lower risk of rehospitalization due to ACS, percutaneous
      transluminal coronary angioplasty, and revascularization than those on statins
      alone. The generalization of the results is limited because of using claims data
      of a specific population as the data source.

PMID- 21872931
TI  - Bioavailability of extended-release nevirapine 400 and 300 mg in HIV-1: a
      multicenter, open-label study.
AB  - BACKGROUND: Nevirapine (NVP) is a widely used non-nucleoside reverse
      transcriptase inhibitor. A once-daily extended-release (XR) formulation would
      potentially increase adherence and thus efficacy. OBJECTIVE: The aim of this
      study was to investigate the steady-state bioavailability of 2 once-daily tablet
      formulations of NVP XR (containing 25% or 20% hypromellose; NVP XR25 and NVP
      XR20, respectively) in 400- or 300-mg tablets compared with twice-daily immediate
      release (IR) NVP 200-mg tablets. METHODS: This Phase Ib multinational,
      multicenter, open-label trial was conducted in patients aged 18 to 60 years,
      infected with HIV-1 (viral load, <=50 copies/mL), and treated for >=12 weeks with
      twice-daily NVP IR 200 mg. Patients were switched to NVP XR25 400 or 300 mg or
      NVP XR20 400 or 300 mg for 19 days. Plasma samples were collected over 24-hour
      periods at steady state. Primary end points were AUC(0-24,ss), C(max,ss), and
      C(min,ss), analyzed using an ANOVA statistical model on the logarithmic scale and
      2-sided 90% CI. Sample size was determined assuming an intrasubject %CV of 20%
      for C(max). Adverse events (AEs) and viral loads were monitored. RESULTS: Ninety
      two patients were enrolled (NVP XR25 400 mg, 24 patients; NVP XR20 400 mg, 24;
      NVP XR25 300 mg, 21; NVP XR20 300 mg, 23). Compared with NVP IR, the AUC(0-24,ss)
      values of the NVP XR formulations were lower (test/reference ratios: 79.5% [90%
      CI, 73.0-86.7; P = 0.544], 71.0% [90% CI, 63.3-79.7; P = 0.956], 90.3% [90% CI,
      80.4-101.4; P = 0.044], and 83.7% [90% CI, 77.9-89.9; P = 0.148] with NVP XR25
      400 mg, NVP XR20 400 mg, NVP XR25 300 mg, and NVP XR20 300 mg, respectively). The
      relative bioavailability of NVP XR25 was greater compared with that of NVP XR20.
      C(max,ss) values were lower with all NVP XR formulations compared with NVP IR.
      For C(min,ss), NVP XR25 400 and 300 mg were not significantly different from NVP
      IR, with 90% CIs within the range of 80% to 125% (P = 0.039 and P = 0.017,
      respectively). All AEs were mild or moderate, with no significant differences
      between treatment groups. No virologic failures (viral load, >50 copies/mL over 2
      consecutive readings) were observed. CONCLUSIONS: Extent of bioavailability was
      lower and t(max,ss) was delayed with all NVP XR formulations compared with NVP
      IR. The bioavailability of the NVP XR25 formulations was greater than that of the
      NVP XR20 formulations. C(min,ss) with NVP XR25 was similar to that with NVP IR.
      All of the NVP XR formulations were well tolerated. The 400-mg NVP XR25
      formulation was selected for further development.

PMID- 21872932
TI  - Differential antiviral activity of Mx1, Mx2 and Mx3 proteins from gilthead
      seabream (Sparus aurata) against Infectious Pancreatic Necrosis Virus (IPNV).
AB  - Mx proteins are crucial effectors of the innate antiviral response mediated by
      the interferon type I signalling pathway. Recently, three Mx proteins, named
      SauMx1, SauMx2 and SauMx3, corresponding to three different genes, have been
      identified in the cultured marine species gilthead seabream (Sparus aurata). In
      this study, the three SauMx cDNAs were cloned into expression vectors and used
      for transfection of CHSE-214 cells. Monoclonal cell populations stably expressing
      each recombinant protein have been obtained and characterized. The protection
      conferred by each recombinant SauMx against Infectious Pancreatic Necrosis Virus
      (IPNV) infection has been in vitro evaluated, having found clear differences
      among them. According to the cytopathic effects and the virus yield reduction
      assays, only cells expressing SauMx2 and SauMx3 showed significant resistance to
      IPNV infection. Otherwise, quantitative RT real-time PCR assays suggested that
      each SauMx protein has a different target during the viral inhibition process.
      The differences observed among the three SauMx proteins are discussed in terms of
      their differential mechanism of action and antiviral specificity, suggesting, as
      a whole, to play a synergistic activity in the protection of gilthead seabream
      against IPNV.

PMID- 21872933
TI  - Astigmatism progression in the early treatment for retinopathy of prematurity
      study to 6 years of age.
AB  - PURPOSE: To examine the prevalence of astigmatism (>= 1.00 diopter [D]) and high
      astigmatism (>= 2.00 D) from 6 months after term due date to 6 years of age in
      preterm children with birth weight of less than 1251 g in whom high-risk
      prethreshold retinopathy of prematurity (ROP) developed and who participated in
      the Early Treatment for ROP study. DESIGN: Observational cohort study.
      PARTICIPANTS: Four hundred one infants in whom high-risk prethreshold ROP
      developed in 1 or both eyes and were randomized to early treatment (ET) versus
      conventional management (CM). Refractive error was measured by cycloplegic
      retinoscopy. Eyes were excluded if they underwent additional retinal, glaucoma,
      or cataract surgery. INTERVENTION: Eyes were randomized to receive laser
      photocoagulation at high-risk prethreshold ROP or to receive treatment only if
      threshold ROP developed. MAIN OUTCOME MEASURES: Astigmatism and high astigmatism
      at each study visit. RESULTS: For both ET and CM eyes, there was a consistent
      increase in prevalence of astigmatism over time, increasing from 42% at 4 years
      to 52% by 6 years for the group of ET eyes and from 47% to 54%, respectively, in
      the CM eyes. There was no statistically significant difference between the slopes
      (rate of change per month) of the ET and CM eyes for both astigmatism and high
      astigmatism (P = 0.75). CONCLUSIONS: By 6 years of age, astigmatism of 1.00 D or
      more developed in more than 50% of eyes with high-risk prethreshold ROP, and
      nearly 25% of such eyes had high astigmatism (>= 2.00 D). Presence of astigmatism
      was not influenced by timing of treatment, zone of acute-phase ROP, or presence
      of plus disease. However, there was a trend toward higher prevalence of
      astigmatism and high astigmatism in eyes with ROP residua. Most astigmatism was
      with-the-rule (75 degrees -105 degrees ). More eyes with type 2 than type 1 ROP
      had astigmatism by 6 years. These findings reinforce the need for follow-up eye
      examinations through early grade school years in infants with high-risk
      prethreshold ROP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 21872934
TI  - Ocular surface morbidity in eyes with senile sunken upper eyelids.
AB  - PURPOSE: To report ocular surface findings in eyes manifesting senile sunken
      upper eyelids. DESIGN: Cross-sectional comparative case series. PARTICIPANTS: A
      study group of 38 eyes of 38 patients with sunken upper eyelids was compared with
      a control group of 26 age- and gender-matched patients without sunken upper
      eyelids. METHODS: Patient records were retrieved and compared between the 2
      groups and among different severities of sunken upper lids. MAIN OUTCOME
      MEASURES: Ocular surface deficits were measured by symptoms, eyelid blinking and
      closure, Bell's phenomenon, apposition of lids and puncta to the globe,
      conjunctiva inflammation and chalasis, corneal epithelial breakdown by
      fluorescein and Rose Bengal staining, and the fluorescein clearance test.
      RESULTS: Ocular irritation or pain was less common, but tearing and mucous
      buildup were more common in the study group than the control group, and it tended
      to be worse in the morning. Incomplete blinking, incomplete closure, abnormal
      Bell's phenomenon, lid/punctum ectropion, and delayed tear clearance were more
      frequently detected in the study group than the control group and were more
      evident in severely affected eyes. Incomplete blinking was significantly
      correlated with incomplete closure, whereas abnormal Bell's phenomenon was
      significantly correlated with early morning symptoms. Conjunctivochalasis was
      less common in the study group than the control group. Corneal epithelial
      breakdown was more common in the study group than the control group, and was more
      severe in severely affected eyes. CONCLUSIONS: Sunken upper eyelids are
      associated with ocular surface morbidity characterized by corneal epithelial
      breakdown because of an array of ocular surface deficits leading to exposure and
      desiccation, not only during the day but also in the night. Recognition of this
      potential risk factor will help to understand pathogenesis and formulate
      effective therapies in complex ocular surface diseases. FINANCIAL DISCLOSURE(S):
      The authors have no proprietary or commercial interest in any of the materials
      discussed in this article.

PMID- 21872935
TI  - Incidence of retinal pigment epithelial tears after intravitreal ranibizumab
      injection for neovascular age-related macular degeneration.
AB  - OBJECTIVE: To explore the association between treatment for neovascular age
      related macular degeneration (AMD) and incidence and timing of retinal pigment
      epithelium (RPE) tears in ranibizumab-treated patients versus control treatment.
      DESIGN: Results from 3 phase III clinical trials (ANti-VEGF antibody for the
      treatment of predominantly classic CHORoidal neovascularization in age-related
      macular degeneration [ANCHOR], Minimally classic/occult trial of the Anti-VEGF
      antibody Ranibizumab In the treatment of Neovascular Age-related macular
      degeneration [MARINA], and A Phase IIIb, Multicenter, Randomized, Double-Masked,
      Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in
      Subjects with Subfoveal Choroidal Neovascularization [CNV] with or without
      Classic CNV Secondary to Age-Related Macular Degeneration [PIER]) were
      retrospectively reviewed to identify patients who developed RPE tears during the
      study period, detected on fluorescein angiography performed at prespecified
      intervals. PARTICIPANTS: Patients with baseline and post-baseline angiographic
      assessments. METHODS: Patients received intravitreal ranibizumab (0.3 or 0.5 mg)
      or control treatment (verteporfin photodynamic therapy [PDT] in ANCHOR and sham
      intravitreal injections in ANCHOR, MARINA, and PIER). MAIN OUTCOME MEASURES:
      Incidence and timing of RPE tears during the treatment period. RESULTS: Data from
      1298 patients were analyzed. No statistically significant differences in RPE tear
      incidence were observed. The pooled rate of RPE tears was 1.8% with 0.5 mg
      ranibizumab, 3.0% with 0.3 mg ranibizumab, and 1.6% in the control group. Most
      (76%; 16/21) RPE tears in ranibizumab-treated patients were identified within 3
      months of initiating treatment, whereas the majority (80%; 4/5) of late-onset RPE
      tears occurred in control patients. In patients who developed RPE tears, better
      visual acuity (VA) outcomes were observed in those treated with ranibizumab
      versus control treatment. CONCLUSIONS: As studied in these trials, no
      statistically significant differences in the incidence of RPE tears within a 2
      year treatment period were observed in patients who received ranibizumab (0.5 or
      0.3 mg) versus control treatment, although most RPE tears with ranibizumab
      occurred within 3 months of initiating treatment. Mean VA was better in patients
      who developed RPE tears while receiving ranibizumab than in those who received
      control treatment, suggesting a potential benefit of continued ranibizumab
      therapy in patients with neovascular AMD who developed RPE tears. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 21872936
TI  - Clinical implications of old and new genes for open-angle glaucoma.
AB  - OBJECTIVE: Genome-wide association studies have revealed new insights into the
      genetic determinants of open-angle glaucoma (OAG). This study was performed to
      determine to what extent variants within established genes (MYOC, OPTN, and
      WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1)
      contribute to the risk of OAG. DESIGN: Population-based setting, family-based
      setting, and a case-control study. PARTICIPANTS: The Rotterdam Study I cohort (N
      = 5312; mean age+/-standard deviation [SD], 68.0+/-8.4 years). Findings were
      replicated in the Genetic Research in Isolated Populations combined with the
      Erasmus Rucphen Family study (N = 1750; mean age+/-SD, 48.3+/-15.2 years), and a
      cohort from Southampton (N = 702; mean age+/-SD, 72.5+/-10.7 years). METHODS:
      After identifying common variants associated with OAG within the established
      genes, the risk of OAG was analyzed using logistic regression. Discriminative
      accuracy was assessed by comparing the area under the receiver operator
      characteristic curve (AUC) for models, including the number of risk alleles,
      intraocular pressure, age, and gender, with the AUC for the same model but
      without the risk alleles. MAIN OUTCOME MEASURES: Odds ratios and AUCs of
      individual and combined risk alleles. RESULTS: No consistent significant
      associations for the established genes (MYOC, OPTN, and WDR36) with OAG were
      found. However, when comparing the load of risk variants between cases and
      controls, 2 of 3 studies showed a significant increased risk of OAG for
      participants carrying more risk alleles of the 3 established genes. When
      combining all 6 genes, participants carrying a high number of risk alleles
      (highest tertile) had a 2.29-fold to 3.19-fold increase in risk of OAG compared
      with those carrying only a few risk alleles. The addition of the newly identified
      genes to IOP, age, and gender resulted in a higher AUC compared with the AUC
      without the newly identified genes (P = 0.027). CONCLUSIONS: A significant
      contribution to the risk of OAG was found for the new common variants identified
      by recent genome-wide association studies, but not for variants within the
      established genes. Participants carrying a high number of risk alleles had an
      approximately 3-fold increase in the risk of OAG compared with those with a low
      number of risk alleles. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 21872937
TI  - Smoking and strabismus surgery in patients with thyroid eye disease.
AB  - OBJECTIVE: To investigate the relationship between smoking status at presentation
      and the use of strabismus surgery in the management of patients with thyroid eye
      disease. DESIGN: Retrospective review of a noncomparative series of patients with
      thyroid eye disease. PARTICIPANTS: All patients with thyroid eye disease under
      the care of a single consultant at Moorfields Eye Hospital between 1997 and 2002
      (inclusive). METHODS: Retrospective review of clinical case notes. MAIN OUTCOME
      MEASURES: Survival analysis of patients in cohort and the frequency of strabismus
      surgery in relation to smoking status at ophthalmic presentation. A subanalysis
      of patients who underwent orbital decompression and those that did not was
      undertaken. RESULTS: Of 501 patients seen during the study period, 425 (85%) of
      501 sets of notes were available for review, and initial smoking status was
      recorded for 89% (378/425) of patients, of whom approximately one half (196/378;
      52%) were active smokers. Of the smokers, 51 (26%) of 196 underwent strabismus
      surgery, compared with only 19 (14%) of 138 nonsmokers at presentation. When
      adjusted for age, the hazards ratio of having strabismus surgery during
      management for smokers at presentation versus nonactive smokers was 2.19. In the
      group who did not undergo orbital decompression, this hazard ratio increased to
      4.86. CONCLUSIONS: Within this thyroid eye disease cohort, the proportion of
      smokers at presentation was much larger than that of the general population.
      There was an increased use of strabismus surgery in active smokers at
      presentation than in nonactive smokers. This finding was independent of the
      orbital decompression surgery. The results are consistent with those of previous
      reports of more severe thyroid eye disease in smokers and raise the possibility
      that smoking cessation early in the disease may reduce the severity of the
      changes and the number of rehabilitative strabismus operations needed. FINANCIAL
      DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 21872938
TI  - Descemet's membrane endothelial keratoplasty: prospective study of 1-year visual
      outcomes, graft survival, and endothelial cell loss.
AB  - PURPOSE: To report 1-year outcomes of Descemet's membrane endothelial
      keratoplasty (DMEK) performed at 2 centers. DESIGN: Prospective, consecutive,
      interventional series. PARTICIPANTS: Patients with Fuchs' endothelial dystrophy,
      pseudophakic bullous keratoplasty, or failed previous graft (n = 136 eyes).
      INTERVENTION: The diseased central 7 mm of Descemet's membrane (DM) was stripped
      from the recipient cornea and replaced with healthy DM and endothelium stripped
      from donor corneas through a 2.8-mm corneal incision. Descemet's membrane
      endothelial keratoplasty was performed alone (n = 110) or combined with either
      phacoemulsification and intraocular lens implantation (n = 23) or pars plana
      vitrectomy (n = 3). MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity
      (BSCVA), manifest refraction, and endothelial cell density. RESULTS: Excluding
      eyes with pre-existing ocular comorbidities or those lost to follow-up, mean
      BSCVA at 1 year was 0.07 logarithm minimum angle of resolution (logMAR) units
      (20/24; range, 20/15-20/40; n = 81), improving from 0.51 logMAR (20/65; range,
      20/20-counting fingers); 41% of the patients achieved a BSCVA of 20/20 or better,
      80% could be corrected to 20/25 or better, and 98% achieved 20/30 or better
      vision. A refractive hyperopic shift of +0.24 +/- 1.01 diopters (D; range, -1.50
      to 2.25 D) was found at 1 year, but it was not statistically significant (P =
      0.08). Also, there was no significant change in the preoperative astigmatism (P =
      0.17). The endothelial cell loss at 1 year was 36 +/- 20% (n = 94; range, 13%
      88%), with most of the loss being observed during the first 3 months after
      surgery: 31 +/- 18% (range, 3%-77%). The DMEK graft creation could not be
      successfully completed in 6 cases (4.2%). All these unsuccessful attempts were
      among the initial 40 cases. Intracameral air was used to fix graft detachments,
      which usually were partial and peripheral, in 62% of the cases. Eleven grafts
      (8%) demonstrated primary failure and 1 eye (0.7%) had secondary failure
      resulting from endothelial rejection. Episodes of immunologic rejection were
      documented in 7 eyes (5.1%) during the first year of follow-up. CONCLUSIONS:
      Descemet's membrane endothelial keratoplasty had better visual acuity results in
      the first year after surgery than typically reported for other endothelial
      keratoplasty techniques, such as Descemet's stripping automated endothelial
      keratoplasty, while having less refractive changes and similar endothelial cell
      counts but a higher rebubbling rate. FINANCIAL DISCLOSURE(S): The author(s) have
      no proprietary or commercial interest in any materials discussed in this article.

PMID- 21872939
TI  - Clinical evaluation of an ultraviolet light adjustable intraocular lens implanted
      after cataract removal: eighteen months follow-up.
AB  - PURPOSE: To determine the effectiveness of a light-adjustable intraocular lens
      (LAL) that can be adjusted postoperatively using ultraviolet (UV) irradiation.
      DESIGN: A prospective, nonrandomized clinical trial was conducted at Center for
      Vision Science, Ruhr University Eye Clinic, in Bochum, Germany. PARTICIPANTS: We
      included 122 eyes of 91 patients with significant cataract. METHODS: All patients
      had a visually significant cataract and were willing to volunteer for the trial.
      Participants underwent small-incision phacoemulsification followed by
      implantation of a LAL and were treated with a spatially profiled UV light
      delivered by a digital light delivery device to induce a targeted spherical and
      cylindrical refractive change postoperatively. Once the desired correction was
      achieved, the LAL was treated again to lock in the lens power. Distance visual
      acuity and manifest refraction was determined with follow-up time to determine
      the achieved refractive corrections and their stability. MAIN OUTCOME MEASURES:
      We measured uncorrected visual acuity and best corrected visual acuity achieved
      versus targeted refractive outcome and refractive stability with a follow-up time
      of 18 months. RESULTS: Residual postoperative refractive errors of 0.96 +/- 0.85
      diopters (D) in sphere and -0.98 +/- 0.50 D in cylinder were corrected and stable
      over a follow-up time of 18 months. Final refraction achieved was 0.03 +/- 0.17 D
      in spherical equivalent refraction. CONCLUSIONS: Residual spherocylindrical
      errors up to 2.25 D in sphere and -2.75D in cylinder were successfully corrected
      with precision. The LAL technology has the potential individually to correct
      postoperative refractive errors precisely. The achieved refractive corrections
      are stable for up to 18 months. FINANCIAL DISCLOSURE(S): The authors have no
      proprietary or commercial interest in any of the materials discussed in this
      article.

PMID- 21872940
TI  - Current practices for mental health follow-up after psychiatric emergency
      department/psychiatric emergency service visits: a national survey of academic
      emergency departments.
AB  - OBJECTIVE: The objective was to describe continuity of care approaches for
      psychiatric emergencies in the emergency department. METHODS: A national survey
      of all 138 academic emergency departments in the United States was conducted.
      RESULTS: Most emergency physicians (81%) had no systematic method for identifying
      psychiatric emergency patients with high recidivism. In order to promote
      outpatient care, sites commonly reported using intensive interventions, including
      scheduling outpatient appointments prior to discharge (72%) and in-house case
      management (64%). CONCLUSION: While systematic identification of repeat
      psychiatric emergency patients was uncommon, emergency departments reported using
      a variety of fairly intensive strategies to promote continuity of care with
      outpatient mental health services.

PMID- 21872941
TI  - History of suicide attempt in male substance-dependent inpatients and
      relationship to borderline personality features, anger, hostility and aggression.
AB  - The aim of this study was to investigate the relationship between severity of
      borderline personality features and history of suicide attempt (HSA) in male
      substance-dependent inpatients and the effect of anger, hostility and aggression
      on this relationship. Further, the effect of some variables that may be related
      to suicide and/or borderline personality, such as age at inception of regular
      substance use, substance of dependence (alcohol/drug), depression, and both state
      and trait anxiety, were controlled. Participants were 200 consecutively admitted
      male substance-dependent inpatients. Patients were investigated with the
      Borderline Personality Inventory (BPI), the Buss-Perry Aggression Questionnaire
      (AQ), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory
      (STAI). Among substance-dependent inpatients, 33.0% (n=66) were identified as the
      group with HSA. Mean scores employment status, marital status and duration of
      education did not differ between groups, whereas current age and age at onset of
      regular substance use were lower in group with HSA. Mean scores of BPI, AQ and
      its subscales (anger, hostility and physical/verbal aggression), BDI and STAI
      were higher in the HSA group. In addition, the rates of drug dependency and
      borderline personality disorder were higher in this group. The severity of
      borderline personality symptoms was highly correlated with subscales of the AQ,
      depression and anxiety, whereas it was negatively correlated with age at onset of
      regular substance use. The severity of anger and borderline personality features
      predicted HSA in the logistic regression model. Results suggest that, to reduce
      the risk of suicide attempt among substance-dependent patients, the feeling of
      anger must be the target of evaluation and treatment among those with borderline
      personality features.

PMID- 21872942
TI  - COMT haplotype analyses in Malaysians with schizophrenia.
AB  - The present study included a total 261 patients with schizophrenia and 261
      healthy controls to replicate the genetic association between the cathechol-o
      methyltransferase gene and schizophrenia using a haplotype block-based gene
      tagging. The G-G-G haplotype was found to show a highly significant association
      with schizophrenia.

PMID- 21872943
TI  - Four cases of anti-ganglioside antibody-positive neuralgic amyotrophy with good
      response to intravenous immunoglobulin infusion therapy.
AB  - Neuralgic amyotrophy (NA), which is an idiopathic disorder in the peripheral
      nerves, is characterized by an acute onset of unilateral pain in the proximal
      limbs followed by muscular weakness and wasting. Some cases of NA are thought to
      be related to immune pathogenic disorders such as Guillain-Barre syndrome (GBS).
      We report the case of four patients with NA who were positive for anti-N
      acetylgalactosaminyl GD1a (anti-GalNAc-GD1a) antibodies, had a preceding
      infection, and showed a good response to intravenous immunoglobulin infusion
      therapy. Anti-ganglioside antibodies, especially the anti-GalNAc-GD1a antibody,
      may be a useful marker for predicting response to immune therapy.

PMID- 21872945
TI  - Right heart characteristics and exercise parameters in adults with Ebstein
      anomaly: new perspectives from cardiac magnetic resonance imaging studies.
AB  - BACKGROUND: The utility of cardiac magnetic resonance imaging (CMR) for
      assessment of adults with Ebstein anomaly is not well-defined. We sought to
      evaluate CMR characteristics in this population and to relate these to exercise
      parameters. METHODS: We analyzed CMR studies in adults with unrepaired Ebstein
      anomaly for measures of severity of Ebstein disease, including atrialized,
      functional and total right ventricular (RV) volumes, ejection fraction (EF) and
      severity index (area of atrialized RV+right atrium/functional RV+left
      ventricle+left atrium). We related these CMR values to cardiopulmonary exercise
      test measurements. RESULTS: Twenty-seven adults (mean age 41 +/- 14 years, 70%
      female) were included. Functional RV end-diastolic volume (EDV) was 150 +/- 68
      mL/m(2) and atrialized RVEDV was 25 +/- 24 mL/m(2). In 17 patients (63%), the
      functional RVEDV was enlarged (>114 mL/m(2)). Percent predicted peak VO2 for the
      population was 65 +/- 20%. On univariable analysis, peak VO2 was inversely
      related to atrialized RVEDV (p = 0.011), total RVEDV (p = 0.041), functional
      RVEDV/left ventricular EDV ratio (p = 0.015) and magnitude of tricuspid valve
      displacement (p = 0.031). In the multivariate model, the only CMR factor to
      relate to peak VO2 was atrialized RVEDV (p = 0.011, beta = -0.48). No significant
      correlations were found between CMR measures and heart rate response or
      ventilatory response to exercise. CONCLUSION: In adults with unrepaired Ebstein
      anomaly, atrialized RV volume was independently related to aerobic capacity. The
      volume of the atrialized RV is a novel CMR measure which may express severity of
      disease. Further research is needed to evaluate the prognostic relevance of this
      exploratory work.

PMID- 21872944
TI  - Organization and development of direction-selective circuits in the retina.
AB  - The direction-selective circuit in the retina extracts the directional
      information of image motion in the visual scene. It is a classic model for neural
      circuit analysis because its input and output are well-defined and accessible to
      physiological measurements. However, the neural basis of direction selectivity is
      still not fully understood. Indeed, this ostensibly simple computation arises
      from a collection of complex neural mechanisms at all levels of circuit
      organization. In this review, we describe recent advances in genetic, imaging and
      optogenetic techniques that have improved our understanding of the synaptic
      organization and development underlying retinal direction selectivity.

PMID- 21872946
TI  - Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart
      failure.
AB  - BACKGROUND: The identification of patients at risk for worse outcome is still a
      challenge. We hypothesized that cystatin C, a marker of renal function, and
      neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute renal
      injury, would have a role in the prognostic stratification of these patients.
      METHODS: We prospectively evaluated 121 patients admitted for acute HF. Serum
      NGAL and cystatin C levels were measured on the first morning after admission.
      The outcome measures used were the occurrence of death from all causes, and the
      combined endpoint defined as the first occurrence of either death or hospital
      admission. Patients were followed for up to 3 months. RESULTS: The variables
      associated with a higher occurrence of death in a univariate approach were older
      age and higher levels of BNP, cystatin C and NGAL, and those associated with the
      occurrence of the combined endpoint were older age, Diabetes mellitus, lower GFR,
      type 1 cardio-renal syndrome, BNP, cystatin C and NGAL. BNP and NGAL remained
      independent predictors of the occurrence of both all-cause death and the combined
      endpoint. NGAL levels in the 75th percentile (>167.5 ng/mL) were associated with
      a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of
      the first occurrence of either death or hospitalization. CONCLUSIONS: Serum NGAL,
      a marker of acute renal injury, is an independent predictor of worse short term
      prognosis in patients with acute HF. This suggests a role of renal damage, apart
      from renal function, in the prognosis of these patients.

PMID- 21872947
TI  - MRI study on volume effects of coronary emboli on myocardial function, perfusion
      and viability.
AB  - BACKGROUND: Coronary filtration devices showed inadequate protection during PCI
      due to the inability to filter microemboli <120 MUm in diameter. The purpose of
      this study was to determine the impact of two volumes of <120 MUm microemboli on
      LV function, perfusion and viability using magnetic resonance imaging (MRI).
      METHODS: Under X-ray guidance, pigs (n = 18) received two different volumes (16
      mm(3) or 32 mm(3)) of 40-120 MUm microemboli (intracoronary). At 3 days, regional
      myocardial perfusion and LV function were assessed using first pass perfusion and
      cine MRI. Viability MRI was performed in beating and non-beating hearts to
      delineate microinfarcts and compare with histochemical triphenyltetrazolium
      chloride stain, using semi-automatic threshold method. Histology and cardiac
      injury enzymes were used to confirm the presence of microinfarcts and
      characterize cellular and vascular changes. RESULTS: Microinfarcts were visible
      as enhanced specks on DE-MRI in all animals that received 32 mm(3), but only two
      third of the animals that received 16 mm(3), volume. The decline in ejection
      fraction and increase in LV volumes and microinfarcts were volume dependent.
      Regional perfusion and contractility were significantly reduced in the LAD
      territory compared with remote myocardium. Histology showed apoptosis, edema,
      inflammation and vascular thrombosis. CONCLUSIONS: Microemboli of <120 MUm have
      deleterious effects on LV function, perfusion and viability and the effects are
      dependent on microemboli volume. Microinfarct visualization is crucial to ensure
      that myocardial dysfunction is related to dislodged microemboli and not only to
      pre-procedural stunning or hibernation. This noninvasive MRI method may help in
      evaluating the effectiveness of coronary filtration devices in protecting
      myocardium from microemboli.

PMID- 21872948
TI  - Professor Xin-fang Wang from China is the Father of Modern Echocardiography.

PMID- 21872949
TI  - Lipid-soluble vitamin C palmitate and protection of human high-density
      lipoprotein from hypochlorite-mediated oxidation.

PMID- 21872950
TI  - Ranking freshwater fish farms for the risk of pathogen introduction and spread.
AB  - A semi-quantitative model is presented to rank freshwater rainbow trout farms
      within a country or region with regards to the risk of becoming infected and
      spreading a specified pathogen. The model was developed to support a risk-based
      surveillance scheme for notifiable salmonid pathogens. Routes of pathogen
      introduction and spread were identified through a process of expert consultation
      in a series of workshops. The routes were combined into themes (e.g. exposure via
      water, mechanical transmission). Themes were weighted based on expert opinion.
      Risk factors for each route were scored and combined into a theme score which was
      adjusted by the weight. The number of sources and consignments were used to
      assess introduction via live fish movements onto the farm. Biosecurity measures
      were scored to assess introduction on fomites. Upstream farms, wild fish and
      processing plants were included in assessing the likelihood of introduction by
      water. The scores for each theme were combined to give separate risk scores for
      introduction and spread. A matrix was used to combine these to give an overall
      risk score. A case study for viral haemorrhagic septicaemia is presented. Nine
      farms that represent a range of farming practices of rainbow trout farms in
      England and Wales are used as worked examples of the model. The model is suited
      to risk rank freshwater salmonid farms which are declared free of the pathogen(s)
      under consideration. The score allocated to a farm does not equate to a
      quantitative probability estimate of the farm to become infected or spread
      infection. Nevertheless, the method provides a transparent approach to ranking
      farms with regards to pathogen transmission risks. The output of the model at a
      regional or national level allows the allocation of surveillance effort to be
      risk based. It also provides fish farms with information on how they can reduce
      their risk score by improving biosecurity. The framework of the model can be
      applied to different production systems which may have other routes of disease
      spread. Further work is recommended to validate the allocated scores. Expert
      opinion was obtained through workshops, where the outputs from groups were single
      point estimates for relative weights of risks. More formal expert opinion
      elicitation methods could be used to capture variation in the experts' estimates
      and uncertainty and would provide data on which to simulate the model
      stochastically. The model can be downloaded (in Microsoft((r))-Excel format) from
      the Internet at: http://www.cefas.defra.gov.uk/6701.aspx.

PMID- 21872951
TI  - Assessing human-dog conflicts in Todos Santos, Guatemala: bite incidences and
      public perception.
AB  - The issues surrounding dog bites are a major public health concern, particularly
      in areas of low income where accessibility to adequate health care, veterinary
      medicine and sufficient management of canine population control is low. An
      understanding of the risk factors associated with human-dog conflicts may be
      important when establishing dog bite and disease prevention strategies. In May
      2008, a census of 12 consociated neighbourhoods in Todos Santos, Guatemala was
      conducted to investigate dog bite incidences and the public perception of free
      roaming dog populations. Approximately 16.5% (78/472) of households reported at
      least one dog bite between May 2006 and May 2008. In total, 85 incidents
      occurred: 49.4% (42/85) with adults (>=18 years) and 50.6% (43/85) children (<18
      years). However, there was no significant difference in cumulative incidence of
      dog bites by victim gender or among age categories, there was a non-significant
      trend of higher cumulative incidence of dog bites in children aged six to 17
      years compared to other age categories. The anatomical location of the bite
      varied, but bites to the legs were the most common (73/85; 85.9%). Of the 85
      reported dog bites, 5.9% (5/85) were from dogs from the victims' own households,
      48.2% (41/85) were from a neighbour's dog, 9.4% (8/85) were from dogs regularly
      seen in the community, and 15.3% (13/85) were from dogs not regularly seen in the
      community; the ownership status of the latter two categories of dogs could not be
      determined. Approximately 21% (18/85) of respondents did not know the type of dog
      that bit. Residents were asked for their opinions on potential problems
      associated with dogs in the community. The majority of respondents strongly
      agreed that dogs posed physical risks (78.8%; 372/472), could transmit infections
      to people (88.6%; 418/472), scared the family (82.4%; 389/472) and were too high
      in number (82.6%; 390/472). There were significant but weak correlations between
      owning a dog and expressing negative perceptions of community dogs (Spearman
      rho<0.13). Reporting of a dog bite was not significantly correlated to expressing
      fear or negative perceptions towards community dogs. A further understanding of
      current programs directed at the prevention of dog bites and means of dog
      population control may help determine appropriate future steps for canine
      management. Conflicts between free roaming dogs and people are a pressing issue
      worldwide, and a focus on prevention strategies through education, rather than
      rapid extermination, would be of benefit.

PMID- 21872952
TI  - Utilizing a combination of molecular and spatial tools to assess the effect of a
      public health intervention.
AB  - Until recently New Zealand had one of the highest rates of human
      campylobacteriosis reported by industrialized countries. Since the introduction
      of a range of control measures in the poultry production chain a reduction in
      human cases of around 50% has been observed nationwide. To inform risk managers a
      combination of spatial, temporal and molecular tools - including minimum spanning
      trees, risk surfaces, rarefaction analysis and dynamic source attribution
      modelling - was used in this study to formally evaluate the reduction in disease
      risk that occurred after the implementation of control measures in the poultry
      industry. Utilizing data from a sentinel surveillance site in the Manawatu region
      of New Zealand, our analyses demonstrated a reduction in disease risk
      attributable to a reduction in the number of poultry-associated
      campylobacteriosis cases. Before the implementation of interventions poultry
      associated cases were more prevalent in urban than rural areas, whereas for
      ruminant-associated cases the reverse was evident. In addition to the overall
      reduction in prevalence, this study also showed a stronger intervention effect in
      urban areas where poultry sources were more dominant. Overall a combination of
      molecular and spatial tools has provided evidence that the interventions aimed at
      reducing Campylobacter contamination of poultry were successful in reducing
      poultry-associated disease and this will inform the development of future control
      strategies.

PMID- 21872953
TI  - Endorectal balloon reduces anorectal doses in post-prostatectomy intensity
      modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: To investigate the effect of an endorectal balloon (ERB)
      on anal wall (Awall) and rectal wall (Rwall) doses in high-dose post
      prostatectomy intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: For
      20 patients, referred for salvage IMRT after prostatectomy for prostate cancer,
      two planning CT-scans were performed: one with and one without an air-filled ERB.
      A planning target volume (PTV) was defined, using international guidelines.
      Furthermore, the Awall and Rwall were delineated. In both the scans, IMRT plans
      were generated with a prescribed dose of 70 Gy. The mean dose (D(mean)), maximum
      dose, minimum dose, and volumes exposed to doses ranging from >= 20 to >= 70 Gy
      (V(20)-V(70)) to the Awall and Rwall were calculated. Finally, inner Rwall
      surface areas exposed to doses ranging from >= 20 to >= 70 Gy (A(20)-A(70)) were
      calculated. Dose-parameters were compared between plans with and without ERB.
      RESULTS: All Awall parameters, except V(70), were significantly reduced by the
      ERB with an overall D(mean) reduction of 6 Gy. Absolute reductions in dose-volume
      parameters varied from 5% to 11%. Significantly reduced Rwall V(30), V(40), and
      A(40) were observed with ERB, irrespective of the target volume size. CONCLUSION:
      ERB application significantly reduces Awall and to a lesser degree Rwall doses in
      high-dose post-prostatectomy IMRT.

PMID- 21872954
TI  - Long-term biochemical control of prostate cancer after standard or hyper
      fractionation: evidence for different outcomes between low-intermediate and high
      risk patients.
AB  - BACKGROUND AND PURPOSE: To report the long-term biochemical control of a non
      randomized trial comparing standard (STD) and hyper-fractionated (HFX) radiation
      schedules for prostate cancer treatment. MATERIALS AND METHODS: Between 1993 and
      2003, 370 patients entered the study; 330/370 (STD: 179; HFX: 151) were evaluable
      for current analysis. Median doses were 79.2 Gy and 74 Gy for HFX (1.2 Gy/fr, two
      daily fractions) and STD (2 Gy/fr), respectively; median follow-up was 7.5 yr.
      The two regimens were compared in terms of biochemical relapse-free survival
      (according to ASTRO definition, bRFS) by univariate (log-rank test) and
      multivariate analyses (Cox regression hazard model). Based on published
      relationships between EQD2 and 5-yr biochemical control, alpha/beta values for
      each subgroup could be estimated. RESULTS: 7.5 yr bRFS were 53.4% (+/- 4.4%, 95%
      CI) and 65.4% (+/- 4.0%) for HFX and STD, respectively (p=0.13); HFX was
      associated with a poorer outcome in NCCN low+intermediate patients (7.5 yr bRFS:
      56.6% vs 73.5%, p=0.048) while no differences were seen for high-risk patients
      (7.5 yr bRFS: 44.1% vs 45.3%). Multivariate analysis revealed that NCCN risk
      grouping (high vs low+intermediate; OR: 0.59, p=0.009) and age (< vs >= 70 yr;
      OR: 0.67, p=0.03) were the main predictors of worse bRFS. In the subgroups of
      low+intermediate-risk patients < 70 yr, the poorer outcome of HFX was more
      evident (7.5 yr bRFS: 47.1% vs 70.9%, p=0.078) while no difference was seen for
      older patients (7.5 yr bRFS: 69.4% vs 72.0%, p=0.76). Our alpha/beta estimates
      differ between low+intermediate-risk and high-risk patients. CONCLUSIONS: The
      bRFS long-term results of this non-randomized trial are consistent with different
      sensitivities to fractionation depending on NCCN risk grouping. The impact of age
      on the outcome of HFX for younger low+intermediate patients is consistent with an
      incomplete repair effect in older patients.

PMID- 21872955
TI  - The cost of radiotherapy in a decade of technology evolution.
AB  - PURPOSE: To quantify changes in radiotherapy costs occurring in a decade of
      medical-technological evolution. MATERIALS AND METHODS: The activity-based
      costing (ABC) model of the University Hospitals Leuven (UHL) radiotherapy (RT)
      department was adapted to current RT standards. It allocated actual resource
      costs to the treatments based on the departmental work-flow and patient mix in
      2009. A benchmark with the former model analyzed the cost increases related to
      changes in RT infrastructure and practice over 10 years. RESULTS: A considerable
      increase in total RT costs was observed, resulting from higher capital
      investments (96%) and personnel cost (103%), the latter dominating the total
      picture. Treatment delivery remains the most costly activity, boosted by the cost
      of improved quality assurance (QA), 23% of total product costs, coming along with
      more advanced RT techniques. Hence, cost increases at the product level are most
      obvious for complex treatments, such as intensity-modulated radiotherapy (IMRT),
      representing cost increases ranging between 38% and 88% compared to conformal
      approaches. CONCLUSIONS: The ABC model provides insight into the financial
      consequences of evolving technology and practice. Such data are a mandatory first
      step in our strive to prove RT cost-effectiveness and thus support optimal
      reimbursement and provision of radiotherapy departments.

PMID- 21872956
TI  - Residual setup errors and dose variations with less-than-daily image guided
      patient setup in external beam radiotherapy for esophageal cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate residual patient setup errors and daily dose
      variations of different less-than-daily image guidance (IG) strategies in the
      delivery of external beam radiotherapy for esophageal cancer. MATERIAL AND
      METHODS: Daily image-guided setup data for 25 consecutive esophageal cancer
      patients treated with helical tomotherapy were evaluated. Seven less-than-daily
      IG strategies with different imaging frequencies were simulated. For each IG
      strategy, the daily residual setup errors were calculated. Using TomoTherapy
      Planned Adaptive software, daily dose variations to the clinical target volume,
      heart, and lungs were evaluated in five representative patients. RESULTS: With 0%
      (60%) IG frequency, the margins required for adequate coverage of the clinical
      target volume were 13 mm (10 mm), 14 mm (11 mm), and 5 mm (5 mm) in the left
      right, superior-inferior, and anterior-posterior directions, respectively. Even
      with 60% IG frequency, 10% of the fractions had more than 10% decrease in the
      dose level covering 95% of the target, and 14% and 13% of the fractions had more
      than 10% increase in total lung volume receiving at least 0.8 Gy per fraction,
      and heart volume receiving at least 1.2 Gy per fraction, respectively.
      CONCLUSION: Substantial residual setup errors would occur for treatment fractions
      without IG even if the most frequent less-than-daily IG strategy was to be used,
      which could lead to significant daily dose variations for the target volume and
      adjacent normal tissues. Daily image guidance is recommended throughout the
      course of treatment in conformal radiotherapy for esophageal cancer.

PMID- 21872957
TI  - Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: potential for
      guiding intensity modulated radiation therapy in overcoming hypoxia-induced
      treatment resistance.
AB  - BACKGROUND AND PURPOSE: Positron emission tomography (PET) imaging with [F-18]
      fluoromisonidazole (FMISO) has been validated as a hypoxic tracer. Head and neck
      cancer exhibits hypoxia, inducing aggressive biologic traits that impart
      resistance to treatment. Delivery of modestly higher radiation doses to tumors
      with stable areas of chronic hypoxia can improve tumor control. Advanced
      radiation treatment planning (RTP) and delivery techniques such as intensity
      modulated radiation therapy (IMRT) can deliver higher doses to a small volume
      without increasing morbidity. We investigated the utility of co-registered FMISO
      PET and CT images to develop clinically feasible RTPs with higher tumor control
      probabilities (TCP). MATERIALS AND METHODS: FMISO-PET images were used to
      determine hypoxic sub-volumes for boost planning. Example plans were generated
      for 10 of the patients in the study who exhibited significant hypoxia. We created
      an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the
      hypoxic sub-volumes. We also varied the boost for two patients. RESULT: A
      significant (mean 17%, median 15%) improvement in TCP is predicted when the
      modest additional boost dose to the hypoxic sub-volume is included. CONCLUSION:
      Combined FMISO-PET imaging and IMRT planning permit delivery of higher doses to
      hypoxic regions, increasing the predicted TCP (mean 17%) without increasing
      expected complications.

PMID- 21872958
TI  - Inactivation of Cronobacter sakazakii by manothermosonication in buffer and milk.
AB  - The inactivation of Cronobacter sakazakii by heat and ultrasound treatments under
      pressure at different temperatures [manosonication (MS) and manothermosonication
      (MTS)] was studied in citrate-phosphate pH 7.0 buffer and rehydrated powdered
      milk. The inactivation rate was an exponential function of the treatment time for
      MS/MTS treatments (35-68  degrees C; 200 kPa of pressure; 117 MUm of amplitude of
      ultrasonic waves) in both media, and for thermal treatments alone when buffer was
      used as heating media. Survival curves of C. sakazakii during heating in milk had
      a concave downward profile. Up to 50  degrees C, the lethality of ultrasound
      under pressure treatments was independent of the treatment temperature in both
      media. At temperatures greater than 64  degrees C in buffer and 68  degrees C in
      milk, the inactivating effect of MTS was equivalent to that of the thermal
      treatments alone at the same temperature. Between 50 and 64 oC for buffer and 50
      and 68  degrees C for milk, the lethality of MTS was the result of a synergistic
      effect, where the total lethal effect was higher than the lethal effect of heat
      added to that of ultrasound under pressure at room temperature. The maximum
      synergism was found at 60  degrees C in buffer and at 56  degrees C in milk. A
      heat treatment of 12 min (60  degrees C) or 4 min of an ultrasound under pressure
      at room temperature treatment (35  degrees C; 200 kPa; 117 MUm) would be
      necessary to guarantee the death of 99.99% of C. sakazakii cells suspended in
      milk. The same level of C. sakazakii inactivation can be achieved with 1.8 min of
      a MTS treatment (60  degrees C; 200 kPa; 117 MUm). Damaged cells were detected
      after heat treatments and after ultrasound under pressure treatments at lethal
      but not at non-lethal temperatures.

PMID- 21872959
TI  - Development of a dynamic growth-death model for Escherichia coli O157:H7 in
      minimally processed leafy green vegetables.
AB  - Escherichia coli O157:H7, an occasional contaminant of fresh produce, can present
      a serious health risk in minimally processed leafy green vegetables. A good
      predictive model is needed for Quantitative Risk Assessment (QRA) purposes, which
      adequately describes the growth or die-off of this pathogen under variable
      temperature conditions experienced during processing, storage and shipping.
      Literature data on behaviour of this pathogen on fresh-cut lettuce and spinach
      was taken from published graphs by digitization, published tables or from
      personal communications. A three-phase growth function was fitted to the data
      from 13 studies, and a square root model for growth rate (MU) as a function of
      temperature was derived: MU=(0.023*(Temperature-1.20))(2). Variability in the
      published data was incorporated into the growth model by the use of weighted
      regression and the 95% prediction limits. A log-linear die-off function was
      fitted to the data from 13 studies, and the resulting rate constants were fitted
      to a shifted lognormal distribution (Mean: 0.013; Standard Deviation, 0.010;
      Shift, 0.001). The combined growth-death model successfully predicted pathogen
      behaviour under both isothermal and non-isothermal conditions when compared to
      new published data. By incorporating variability, the resulting model is an
      improvement over existing ones, and is suitable for QRA applications.

PMID- 21872960
TI  - Heat stress leads to superoxide formation in Bacillus cereus detected using the
      fluorescent probe MitoSOX.
AB  - Bacillus cereus is a food-borne human pathogen and food spoilage organism. Spores
      and vegetative cells of B. cereus can be found almost everywhere and therefore
      often end up in food processing equipment and food products. To remove spores and
      vegetative cells from food or equipment, harsh treatments such as high
      temperatures are applied. The heat stress response of B. cereus and other
      organisms has been studied and it has been shown that reactive oxygen species may
      be involved in inactivating the bacterial cells. Using a novel approach with the
      fluorescent probe MitoSOX, the formation of superoxide in B. cereus cells upon
      exposure to heat has been confirmed. MitoSOX can be used in combination with
      other probes, including, SYTOX green, CYTO 9, and CFDA, showing superoxide
      formation in combination with damaged cell membranes, intact cell membranes, and
      esterase activity in cells with intact membranes, respectively. MitoSOX in
      combination with flow cytometry-assisted sorting showed three distinct
      populations, a low fluorescent population that was still viable, a highly
      fluorescent population that could not be recovered on agar plates, and a low
      fluorescent non-viable population that appeared after prolonged exposure to heat.
      This third population may include dead cells where MitoSOX binds to DNA without
      reacting with superoxide. Superoxide formation during exposure to lethal
      temperatures by B. cereus shows that superoxide plays a role in bacterial cell
      death and its generation may thus contribute to the efficiency of food
      preservation conditions.

PMID- 21872961
TI  - Salmonella status of pigs at slaughter--bacteriological and serological analysis.
AB  - Apart from Salmonella monitoring of pig herds during the period of growth to
      evaluate the efficacy of control programmes, monitoring at harvest level is of
      relevance to assess the Salmonella status of fattening pigs and the associated
      risk of introducing Salmonella organisms in the slaughter process. Samples from
      1830 fattening pigs were gathered at slaughter. Ileocaecal lymph nodes, rectal
      and caecal content as well as tonsils were collected for bacteriological
      examinations, and a part of the diaphragm pillar muscle was taken to gain meat
      juice for serological analysis. Salmonella spp. was recovered from 13.8% of all
      pigs examined. Salmonella Typhimurium and Derby were the dominating serovars. The
      highest detection rates were found in caecal content followed by ileocaecal lymph
      nodes. By analysing both organs nearly 90% of all Salmonella positive pigs could
      be identified. Serological examination revealed 9.6% of the pigs as positive
      using a cut-off value of OD % >= 40. Only one quarter of all Salmonella positive
      pigs showed also a positive serological result. A reduction of the cut-off value
      does not necessarily result in a higher compliance between bacteriologically and
      serologically positive slaughter pigs. Detection of antibodies is useful to
      verify whether pig herds were previously exposed to Salmonella organisms.
      However, the Salmonella status of pigs at time of slaughter and the associated
      risk of dissemination of Salmonella organisms can only be assessed by
      bacteriological examinations which should include both lymph nodes and caecal
      content.

PMID- 21872962
TI  - Sustaining short-term improvements over the long-term: results from a 2-year
      diabetes self-management support (DSMS) intervention.
AB  - AIM: This study examined the long-term impact of a 24-month, empowerment-based
      diabetes self-management support (DSMS) intervention on sustaining health-gains
      achieved from previous diabetes self-management education (DSME). METHODS: Prior
      to the intervention, all participants received 6 months of mailed DSME consisting
      of weekly educational newsletters coupled with clinical feedback. The
      intervention consisted of 88 weekly group-based sessions that participants were
      encouraged to attend as frequently as they needed. Sessions were guided by
      participants' self-management questions and also emphasized experiential
      learning, coping, goal-setting, and problem-solving. Baseline, 6-month, and 30
      month assessments measured A1C, weight, body mass index (BMI), blood pressure,
      lipids, self-care behaviors, and QOL. RESULTS: This report is based on 60 African
      American adults with type 2 diabetes (n=89 recruited at baseline) who completed
      the study. Post 6-month DSME, participants demonstrated significant improvements
      for diastolic BP (p<0.05), serum cholesterol (p<0.001), healthy diet (p<0.01),
      blood glucose monitoring (p<0.05) and foot exams (p<0.01). Post 24-month
      intervention, participants sustained the improvements achieved from the 6-month
      DSME and reported additional improvements for healthy diet (p<0.05), carbohydrate
      spacing (p<0.01), insulin use (p<0.05), and quality of life (p<0.05).
      CONCLUSIONS: Findings suggest that an empowerment-based DSMS model can sustain or
      improve diabetes-related health gains achieved from previous short-term DSME.

PMID- 21872964
TI  - The molecular origins of evolutionary innovations.
AB  - The history of life is a history of evolutionary innovations, qualitatively new
      phenotypic traits that endow their bearers with new, often game-changing
      abilities. We know many individual examples of innovations and their natural
      history, but we know little about the fundamental principles of phenotypic
      variability that permit new phenotypes to arise. Most phenotypic innovations
      result from changes in three classes of systems: metabolic networks, regulatory
      circuits, and macromolecules. I here highlight two important features that these
      classes of systems share. The first is the ubiquity of vast genotype networks -
      connected sets of genotypes with the same phenotype. The second is the great
      phenotypic diversity of small neighborhoods around different genotypes in
      genotype space. I here explain that both features are essential for the
      phenotypic variability that can bring forth qualitatively new phenotypes. Both
      features emerge from a common cause, the robustness of phenotypes to
      perturbations, whose origins are linked to life in changing environments.

PMID- 21872963
TI  - The aneuploidy paradox: costs and benefits of an incorrect karyotype.
AB  - Aneuploidy has a paradoxical effect on cell proliferation. In all normal cells
      analyzed to date, aneuploidy has been found to decrease the rate of cell
      proliferation. Yet, aneuploidy is also a hallmark of cancer, a disease of
      enhanced proliferative capacity, and aneuploid cells are frequently recovered
      following the experimental evolution of microorganisms. Thus, in certain
      contexts, aneuploidy might also have growth-advantageous properties. New models
      of aneuploidy and chromosomal instability have shed light on the diverse effects
      that karyotypic imbalances have on cellular phenotypes, and suggest novel ways of
      understanding the role of aneuploidy in development and disease.

PMID- 21872965
TI  - The platelet-derived growth factor system in renal disease: an emerging role of
      endogenous inhibitors.
AB  - The platelet-derived growth factor (PDGF) family consists of four isoforms which
      are secreted as homodimers (PDGF-AA, PDGF-BB, PDGF-CC and PDGF-DD) or
      heterodimers (PDGF-AB), and two receptor chains (PDGFR-alpha and -beta). All
      members of the PDGF system are constitutively or inducibly expressed in renal
      cells and are involved in the regulation of cell proliferation and migration, the
      accumulation of extracellular matrix proteins and the secretion of pro- and anti
      inflammatory mediators. Particular roles have been identified in mediating
      mesangioproliferative changes, renal interstitial fibrosis and glomerular
      angiogenesis. Different endogenous inhibitors of PDGF-induced biological
      responses exist which affect the activation/deactivation of PDGF isoforms, the
      activity of the PDGFRs, or which block downstream signaling pathways of the
      autophosphorylated PDGFRs. The novel endogenous inhibitor nephroblastoma
      overexpressed gene (NOV, CCN3) reduces PDGF-induced cell proliferation and is
      downregulated by PDGF isoforms itself. Among all identified inhibitors only few
      "true" PDGF antagonists have been identified. A better understanding of these
      inhibitors may aid in the design of novel therapeutic approaches to PDGF-mediated
      diseases.

PMID- 21872966
TI  - Binding sites in membrane proteins--diversity, druggability and prospects.
AB  - The identification of novel drug targets is one of the major challenges in
      proteomics. Computational methods developed over the last decade have enhanced
      the process of drug design in both terms of time and quality. The main task is
      the design of selective compounds, which bind targets more specifically,
      dependent on the desired mode of action of the particular drug. This makes it
      necessary to create compounds, which either exhibit their functions on one single
      protein to exclude undesired cross-reactivity or to use the advantageous effect
      of less selective drugs that target numerous proteins and therefore exhibit their
      functions on whole protein classes. Main aspects in the assignment of
      interactions between ligands and putative targets involve the amino acid
      composition of the binding site, evolutionary conservation and similarity in
      sequence and structure of known targets. Similarities or differences within
      classified protein families can be the key to their function and give first hints
      to functional drug design. Hereby, binding site-based classification outnumbers
      sequence-based classifications since similar binding sites can also be found in
      more distant proteins. Membrane proteins are 'difficult targets', because of
      their special physicochemical characteristics and the general lack of structural
      information. Here, we describe recent advances in modeling methods dedicated to
      membrane proteins. Different descriptors of similarity between compounds and the
      similarity between binding sites are under development and elucidate important
      aspects like dynamics or entropy. The importance of computational drug design is
      undisputable. Nevertheless, the process of design is complicated by increasing
      complexity, which underlines the importance of accurate knowledge about the
      addressed target class(es) and particularly their binding sites. One main
      objective by considering named topics is to predict putative side effects and
      errant functions (off-target effects) of novel drugs, which requires a holistic
      (systems biology) view on drug-target-pathway relations. In the following, we
      give a brief summary about the recent discussion on drug-target interactions with
      emphasis on membrane proteins.

PMID- 21872967
TI  - Expression of flavonoid biosynthesis genes vis-a-vis rutin content variation in
      different growth stages of Fagopyrum species.
AB  - Buckwheat is one of the field crops with the highest concentration of rutin, an
      important flavonoid of medicinal value. Two species of buckwheat, Fagopyrum
      esculentum and Fagopyrum tataricum, are the major sources of rutin. Seeds of
      latter contain 40-50* higher rutin compared to the former. The physiological and
      molecular bases of rutin content variation between Fagopyrum species are not
      known. The current study investigated the differences in rutin content in seeds
      and in other tissues and growth stages of two Fagopyrum species, and also
      correlated those differences with the expression of flavonoid pathway genes. The
      analysis of rutin content dynamics at different growth stages, S1-S9 (from seed
      germination to mature seed formation) of Fagopyrum species revealed that rutin
      content was higher during seedling stages of F. tataricum (3.5 to 4.6-fold)
      compared to F. esculentum and then increased exponentially from stages S3 to S6
      (different leaf maturing stages and inflorescence) of F. esculentum, whereas it
      fluctuated in F. tataricum. The rutin content was highest in the inflorescence
      stage (S6) of both species, with a relatively higher biosynthesis and
      accumulation during post-flowering stages of F. tataricum compared to F.
      esculentum. The expression of flavonoid pathway genes, through qRT-PCR, in
      different growth stages vis-a-vis rutin content variation showed differential
      expression for four genes, PAL, CHS, CHI and FLS with the amounts of transcripts
      relatively higher in F. tataricum compared to F. esculentum, thereby, correlating
      these genes with the biosynthesis and accumulation of rutin. The expression of
      PAL was highest, 7.69 and 8.96-fold in Stages 2 (seedling stage) and 9 (fully
      developed seeds) of F. tataricum compared to F. esculentum, respectively. The
      expression of the CHS gene correlated with the rutin content because it was
      highest in the flowers (S6) and fully developed seeds (S9) of both Fagopyrum
      species, with relatively higher transcript amounts (2.13 and 3.19-fold,
      respectively) in F. tataricum (IC-329457) compared to F. esculentum (IC-540858).
      This study provides useful information on molecular and physiological dynamics of
      rutin biosynthesis and accumulation in Fagopyrum species and the correlation of
      expression of flavonoid biosynthesis genes with the rutin content can be useful
      in planning for genetic improvement.

PMID- 21872968
TI  - The subcellular localization of periwinkle farnesyl diphosphate synthase provides
      insight into the role of peroxisome in isoprenoid biosynthesis.
AB  - Farnesyl diphosphate (FPP) synthase (FPS: EC.2.5.1.1, EC.2.5.1.10) catalyzes the
      formation of FPP from isopentenyl diphosphate and dimethylallyl diphosphate via
      two successive condensation reactions. A cDNA designated CrFPS, encoding a
      protein showing high similarities with trans-type short FPS isoforms, was
      isolated from the Madagascar periwinkle (Catharanthus roseus). This cDNA was
      shown to functionally complement the lethal FPS deletion mutant in the yeast
      Saccharomyces cerevisiae. At the subcellular level, while short FPS isoforms are
      usually described as cytosolic proteins, we showed, using transient
      transformations of C. roseus cells with yellow fluorescent protein-fused
      constructs, that CrFPS is targeted to peroxisomes. This finding is discussed in
      relation to the subcellular distribution of FPS isoforms in plants and animals
      and opens new perspectives towards the understanding of isoprenoid biosynthesis.

PMID- 21872969
TI  - Analysis of automated external defibrillator device failures reported to the Food
      and Drug Administration.
AB  - STUDY OBJECTIVE: Automated external defibrillators are essential for treatment of
      cardiac arrest by lay rescuers and must determine when to shock and if they are
      functioning correctly. We seek to characterize automated external defibrillator
      failures reported to the Food and Drug Administration (FDA) and whether battery
      failures are properly detected by automated external defibrillators. METHODS: FDA
      adverse event reports are catalogued in the Manufacturer and User Device
      Experience (MAUDE) database. We developed and internally validated an instrument
      for analyzing MAUDE data, reviewing all reports in which a fatality occurred. Two
      trained reviewers independently analyzed each report, and a third resolved
      discrepancies or passed them to a committee for resolution. RESULTS: One thousand
      two hundred eighty-four adverse events were reported between June 1993 and
      October 2008, of which 1,150 were failed defibrillation attempts. Thirty-seven
      automated external defibrillators never powered on, 252 failed to complete rhythm
      analysis, and 524 failed to deliver a recommended shock. In 149 cases, the
      operator disagreed with the device's rhythm analysis. In 54 cases, the
      defibrillator stated the batteries were low and in 110 other instances powered
      off unexpectedly. Interrater agreement between reviewers 1 and 2 ranged by
      question from 69.0% to 98.6% and for most likely cause was 55.9%. Agreement was
      obtained for 93.7% to 99.6% of questions by the third reviewer. Remaining
      discrepancies were resolved by the arbitration committee. CONCLUSION: MAUDE
      information is often incomplete and frequently no corroborating data are
      available. Some conditions not detected by automated external defibrillators
      during self-test cause units to power off unexpectedly, causing defibrillation
      delays. Backup units frequently provide shocks to patients.

PMID- 21872970
TI  - Intravenous access during out-of-hospital emergency care of noninjured patients:
      a population-based outcome study.
AB  - STUDY OBJECTIVE: Advanced, out-of-hospital procedures such as intravenous access
      are commonly performed by emergency medical services (EMS) personnel, yet little
      evidence supports their use among noninjured patients. We evaluate the
      association between out-of-hospital, intravenous access and mortality among
      noninjured, non-cardiac arrest patients. METHODS: We analyzed a population-based
      cohort of adult (aged >=18 years) noninjured, non-cardiac arrest patients
      transported by 4 advanced life support agencies to one of 16 hospitals from
      January 1, 2002, until December 31, 2006. We linked eligible EMS records to
      hospital administrative data and used multivariable logistic regression to
      determine the risk-adjusted association between out-of-hospital intravenous
      access and hospital mortality. We also tested whether this association differed
      by patient acuity by using a previously published, out-of-hospital triage score.
      RESULTS: Among 56,332 eligible patients, half (N=28,078; 50%) received out-of
      hospital intravenous access from EMS personnel. Overall hospital mortality for
      patients who did and did not receive intravenous access was 3%. However, in
      multivariable analyses, the placement of out-of-hospital, intravenous access was
      associated with an overall reduction in odds of hospital mortality (odds
      ratio=0.68; 95% confidence interval [CI] 0.56 to 0.81). The beneficial
      association of intravenous access appeared to depend on patient acuity (P=.13 for
      interaction). For example, the odds ratio of mortality associated with
      intravenous access was 1.38 (95% CI 0.28 to 7.0) among patients with lowest
      acuity (score=0). In contrast, the odds ratio of mortality associated with
      intravenous access was 0.38 (95% CI 0.17 to 0.9) among patients with highest
      acuity (score >=6). CONCLUSION: In this population-based cohort, out-of-hospital
      efforts to establish intravenous access were associated with a reduction in
      hospital mortality among noninjured, non-cardiac arrest patients with the highest
      acuity. Reasons why this occurred (cause and effect) could not be determined in
      this model.

PMID- 21872971
TI  - Arylazolylthioacetanilide. Part 8: Design, synthesis and biological evaluation of
      novel 2-(2-(2,4-dichlorophenyl)-2H-1,2,4-triazol-3-ylthio)-N-arylacetamides as
      potent HIV-1 inhibitors.
AB  - The development of novel HIV-1 NNRTIs offers the possibility of generating novel
      structures with increased potency. Based on the bioisosteric principle, a novel
      series of 2-(2-(2,4-dichlorophenyl)-2H-1,2,4-triazol-3-ylthio)-N-arylacetamide
      derivatives were designed, synthesized using a simple and efficient synthetic
      route, structurally confirmed by spectral analysis, evaluated for their anti-HIV
      activity in MT-4 cells and their inhibitory effect on HIV-1 RT. The results
      showed that some of the new compounds displayed low micromolar potency for
      inhibiting HIV-1 replication and promising activities against several selected
      resistant strains that confer resistance to current NNRTIs. However, all newly
      synthesized derivatives were not active against HIV-2 replication.

PMID- 21872972
TI  - Combined effects of antioxidant vitamin and NOS3 genetic polymorphisms on breast
      cancer risk in women.
AB  - BACKGROUND & AIMS: It is becoming increasingly clear that there is wide
      heterogeneity in genetic predisposition to breast cancer and that breast cancer
      risk is determined by interactive effect between genetic and environmental
      factors. METHODS: We investigated the combined effects of antioxidant vitamin
      intake and NOS3 genetic polymorphisms on breast cancer risk in a Korean
      population (Seoul Breast Cancer Study). Histologically confirmed breast cancer
      cases (n = 512) and age, menopause status-matched controls (n = 512) with no
      present or previous history of cancer were recruited from several teaching
      hospitals in Seoul during 2001-2003. Two genetic polymorphisms of NOS3 (298G > T
      and -786 T > C) were assessed by single base extension assays. RESULTS: No
      overall association between the individual NOS3 genotypes or diplotypes and
      breast cancer risk was found, although the difference between cases and controls
      in the frequency of the NOS3 894 G > T polymorphism showed borderline
      significance (OR = 0.74, 95% CI = 0.52-1.06). There was no significant difference
      in energy intake or the intake of antioxidant vitamins between cases and
      controls, with the exception of vitamin E (OR = 0.49 lowest vs. highest quartile,
      P(trend) < 0.01). On the other hand, our results suggest that antioxidant vitamin
      intake may modify the effects of the NOS3 -786 T > C or 894 G > T genetic
      polymorphisms on breast cancer risk. Although a multiplicative interaction was
      not observed, the protective effect of beta-carotene intake on breast cancer risk
      was observed predominantly in individuals with the TG:TG diplotype of NOS3 (OR =
      0.68) but not observed with others diplotype. An inverse association between
      vitamin E intake and breast cancer risk was observed for individuals with the
      NOS3 786 TC + TT genotype and the NOS3 894 GG genotype. In addition, folic acid
      had a protective effect in the NOS3 786 TT and NOS3 894 GT + TT genotype.
      CONCLUSION: Our results suggest that intake of antioxidant vitamins might modify
      the association between genetic polymorphisms of NOS3 and breast cancer risk.

PMID- 21872973
TI  - Impact of restrictive diets on the risk of undernutrition in a free-living
      elderly population.
AB  - BACKGROUND & AIMS: Elderly subjects are at risk for undernutrition. Restrictive
      diets may increase this risk. The aim was to evaluate the impact of restrictive
      diets on undernutrition and its risk in free-living elderly. METHODS: Ambulatory
      patients over age 75 and under a restrictive diet (low salt, low cholesterol,
      diabetic) were included prospectively, along with age- and gender-matched
      controls. Weight and height were measured, and the short-form of the Mini
      Nutritional Assessment was scored. Groups were compared to determine variables
      associated with a low MNA-SF((r)). RESULTS: 95 patients in the diet group (62 F,
      33 M, 80 +/- 4 y) and 95 controls (57 F, 38 M, 82 +/- 5 y) were included.
      Restrictive diets (low salt n = 33, diabetic n = 19, low cholesterol n = 15,
      combination n = 27) had been followed since 11.0 +/- 5.9 years. Using the cut-off
      of 12 for MNA-SF((r)), 44 patients in the diet group were at risk vs. 22 among
      controls (P < 0.001). In multivariate analysis, a restrictive diet increased the
      probability of having an MNA-SF((r)) < 12 (OR = 3.6, (95%)CI = 1.8-7.2, P <
      .001). CONCLUSIONS: Restrictive diets in patients over 75 increase the risk of
      undernutrition. On an individual level, these diets may need reassessment.
      Society guidelines should promote specific recommendations for the elderly.

PMID- 21872974
TI  - Testing the resistance of fullerenes to chemothermal oxidation used to isolate
      soots from environmental samples.
AB  - We tested the resistance of five different fullerenes (C(60), C(70), C(76/78)
      mix, and C(84)) to chemothermal oxidation at 375  degrees C (CTO-375), a method
      that has been used and tested for quantifying black carbon (BC) and CNTs in soils
      and sediments. C(60) survived CTO-375 the most (50%), while C(70) was the
      fullerene with the lowest survival rate (<1%). Standard additions of C(60) to
      soil and sediment reference materials yielded recoveries between 18 and 36%.
      Although lower than recoveries previously observed for soot and CNTs, these
      results demonstrate the capability of CTO-375 to partially isolate C(60) from
      solid environmental matrices. Standard additions of C(70), C(76/78), and C(84)
      yielded slightly higher survival rates when added to soil and sediment than in
      their pure form. These results indicate that the mineral matrices of these
      samples probably had a catalytic effect towards C(60) and a protective effect
      towards C(70), C(76/78), and C(84) during CTO-375.

PMID- 21872975
TI  - Mechanisms of purple moor-grass (Molinia caerulea) encroachment in dry heathland
      ecosystems with chronic nitrogen inputs.
AB  - We analysed growth strategies (biomass allocation, nutrient sequestration and
      allocation) of heather (Calluna vulgaris) and purple moor-grass (Molinia
      caerulea) seedlings in monocultures and mixtures in relation to N, P, and N + P
      fertilisation in a greenhouse experiment in order to simulate a heath's pioneer
      phase under high airborne nitrogen (N) loads. N fertilisation increased the total
      biomass of both species in monocultures. In mixtures, M. caerulea sequestered
      about 65% of the N applied, while C. vulgaris suffered from N shortage (halving
      of the total biomass). Thus, in mixtures only M. caerulea will benefit from
      airborne N loads, and competition will become increasingly asymmetric with
      increasing N availability. Our results demonstrate that the heath's pioneer phase
      is the crucial tipping point at which the competitive vigour of M. caerulea (high
      belowground allocation, efficient use of belowground resources, shortened
      reproductive cycles) induces a shift to dominance of grasses under increased N
      availability.

PMID- 21872976
TI  - The biodegradation of cable oil components: impact of oil concentration, nutrient
      addition and bioaugmentation.
AB  - The effect of cable oil concentration, nutrient amendment and bioaugmentation on
      cable oil component biodegradation in a pristine agricultural soil was
      investigated. Biodegradation potential was evaluated over 21 d by measuring
      cumulative CO(2) respiration on a Micro-Oxymax respirometer and (14)C
      phenyldodecane mineralisation using a (14)C-respirometric assay. Cable oil
      concentration had a significant effect upon oil biodegradation. Microbial
      respiratory activity increased with increasing cable oil concentration, whereas
      (14)C-phenydodecane mineralisation decreased. Bioaugmentation achieved the best
      cable oil biodegradation performance, resulting in increases in cumulative CO(2)
      respiration, and maximum rates and extents of (14)C-phenyldodecane
      mineralisation. Generally, nutrient amendment also enhanced cable oil
      biodegradation, but not to the extent that degrader amendment did. Cable oil
      biodegradation was a function of (i) cable oil concentration and (ii) catabolic
      ability of microbial populations. Bioaugmentation may enhance cable oil
      biodegradation, and is dependent upon composition, cell number and application of
      catabolic inocula to soil.

PMID- 21872978
TI  - Coiled versus straight peritoneal dialysis catheters: a randomized controlled
      trial and meta-analysis.
AB  - BACKGROUND: Variations in peritoneal dialysis catheter design include differences
      in numbers of cuffs, shapes of subcutaneous paths (swan neck vs Tenckhoff), and
      shapes of intra-abdominal segments (straight vs coiled). The relative benefits of
      these designs have not been studied adequately. The objective of this study is to
      compare the clinical outcomes of coiled- versus straight-end swan neck peritoneal
      dialysis catheters. STUDY DESIGN: Prospective randomized controlled trial (RCT);
      results were meta-analyzed with other RCTs of coiled versus straight catheters.
      SETTING & PARTICIPANTS: 80 consecutive continuous ambulatory peritoneal dialysis
      patients were enrolled in the RCT. The meta-analysis considers data for 242
      patients with coiled and 251 patients with straight catheters. INTERVENTION:
      Patients were randomly assigned to a coiled-end swan neck catheter (n = 40) or a
      straight-end swan neck catheter (n = 40) group. OUTCOMES: Catheter tip migration
      with dysfunction (primary outcome) and catheter failure, catheter-related
      infection, technique failure, and all-cause mortality (secondary outcomes).
      RESULTS: The primary outcome occurred in 18 patients in the coiled group and 9 in
      the straight group. This difference was not statistically significant (HR, 1.96;
      95% CI, 0.88-4.37; P = 0.09). Although rates of early (<8 weeks) catheter tip
      migration were similar between the 2 groups, we detected a significant
      association of the coiled design with increased risk of late (>8 weeks) catheter
      tip migration (HR, 6.43; 95% CI, 1.45-28.6; P = 0.005). The increased risk of
      overall catheter failure in the coiled group was not statistically significant (P
      = 0.06). In the meta-analysis, coiled catheters were associated significantly
      with increased risk of catheter tip migration (based on 4 trials: RR, 2.08; 95%
      CI, 1.30-3.33; P = 0.002). LIMITATIONS: Single-center open-label experimental
      study powered to detect differences in only the most common complication of
      catheter tip migration with dysfunction. Our RCT examines only swan neck
      catheters, whereas the meta-analysis considers both swan neck and Tenckhoff
      designs. CONCLUSIONS: Although we were unable to show statistically significant
      differences in the primary outcome in our RCT, pooled meta-analysis results
      suggest that coiled catheters may be more prone to migration and resultant
      dysfunction.

PMID- 21872977
TI  - Venous thromboembolism in patients with reduced estimated GFR: a population-based
      perspective.
AB  - BACKGROUND: An increased frequency of venous thromboembolism (VTE) has been shown
      in patients with decreased kidney function measured by decreased estimated
      glomerular filtration rate (eGFR). However, present practices with respect to VTE
      prevention and management in patients with decreased eGFR in general population
      settings are uncertain. STUDY DESIGN: Observational study. SETTING &
      PARTICIPANTS: Community investigation of 1,509 metropolitan Worcester, MA,
      residents with a validated VTE in 1999, 2001, and 2003 with further follow-up for
      up to 3 years. PREDICTOR: Patients with VTE classified further according to eGFR
      on presentation: <30, 30-59, 60-89, or >=90 mL/min/1.73 m(2) (reference group).
      OUTCOMES: Recurrent VTE, major bleeding episodes, and all-cause mortality.
      MEASUREMENTS: Demographic and clinical characteristics, treatment practices, and
      study outcomes were extracted from patients' hospital and outpatient medical
      records; eGFR was estimated using the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equation. RESULTS: Patients with VTE with eGFR <30
      mL/min/1.73 m(2) were at increased risk of recurrent VTE (HR, 1.83; 95% CI, 1.03
      3.25), major bleeding episodes (HR, 2.30; 95% CI, 1.28-4.16), and all-cause
      mortality (HR, 1.70; 95% CI, 1.12-2.57) during a 3-year follow-up. Patients with
      decreased eGFR also presented with more comorbid conditions and were less likely
      to be discharged on any form of anticoagulant therapy (72.6%, 81.0%, 82.1%, and
      87.3% for eGFR <30, 30-59, 60-89, and >=90 mL/min/1.73 m(2), respectively; P <
      0.001). LIMITATIONS: Decreased eGFR status is presumed based on creatinine values
      on clinical presentation. The impact of drug dosage, timing, type of
      anticoagulant therapy, and medication adherence on study outcomes could not be
      evaluated. CONCLUSIONS: Severe decreases in eGFR are associated with increased
      risk of long-term recurrent VTE, bleeding, and total mortality in patients with
      VTE. A greater frequency of serious comorbid conditions, difficulties
      implementing available management strategies, and suboptimal VTE prophylaxis
      during hospital admissions likely contributed to our findings.

PMID- 21872979
TI  - beta-Blockers for prevention of sudden cardiac death in patients on hemodialysis:
      a propensity score analysis of the HEMO Study.
AB  - BACKGROUND: Hemodialysis patients have an elevated risk of sudden cardiac death.
      Although the efficacy of beta-blockers for the prevention of sudden cardiac death
      has been proven in the general population, little evidence exists in patients
      with kidney failure. STUDY DESIGN: Post hoc analysis of the Hemodialysis (HEMO)
      Study. SETTING & PARTICIPANTS: Participants enrolled in the HEMO Study from May
      1995 to February 2001. INTERVENTION: beta-Blocker use ascertained through self
      reported questionnaires and dialysis clinic charts. OUTCOMES: Sudden cardiac
      death adjudicated by a committee as a secondary outcome of interest.
      MEASUREMENTS: We used Cox proportional hazards regression models, competing risk
      survival analysis, propensity score matching, and covariate adjustment to study
      the association of beta-blockers with sudden cardiac death. RESULTS: 1,747
      patients were included in this study, and 521 were on beta-blocker therapy at
      baseline. Mean age was 58 years, 57% were women, and 39% had ischemic heart
      disease (IHD) at baseline. Baseline beta-blocker use was not associated with
      lower risk of sudden cardiac death in univariate (cause-specific HR, 0.89; 95%
      CI, 0.64-1.24), multivariable (cause-specific HR, 0.87; 95% CI, 0.62-1.22), or
      propensity-matched (cause-specific HR, 0.91; 95% CI, 0.55-1.50) analyses. There
      was a significant interaction between beta-blocker use and sudden cardiac death
      (interaction P = 0.03) in patients with (cause-specific HR, 0.65; 95% CI, 0.42
      1.01) and without IHD (cause-specific HR, 1.61; 95% CI, 0.92-2.80). LIMITATIONS:
      Observational nature of the study. CONCLUSIONS: In hemodialysis patients without
      preexisting IHD, beta-blocker use was not associated with lower risk of sudden
      cardiac death. However, there was a trend toward benefit in those with IHD.

PMID- 21872980
TI  - Partial anomalous pulmonary venous drainage and Mayer-Rokitansky-Kuster-Hauser
      syndrome.

PMID- 21872981
TI  - [Propensity score methods for creating covariate balance in observational
      studies].
AB  - Randomization of treatment assignment in experiments generates treatment groups
      with approximately balanced baseline covariates. However, in observational
      studies, where treatment assignment is not random, patients in the active
      treatment and control groups often differ on crucial covariates that are related
      to outcomes. These covariate imbalances can lead to biased treatment effect
      estimates. The propensity score is the probability that a patient with particular
      baseline characteristics is assigned to active treatment rather than control.
      Though propensity scores are unknown in observational studies, by matching or
      subclassifying patients on estimated propensity scores, we can design
      observational studies that parallel randomized experiments, with approximate
      balance on observed covariates. Observational study designs based on estimated
      propensity scores can generate approximately unbiased treatment effect estimates.
      Critically, propensity score designs should be created without access to
      outcomes, mirroring the separation of study design and outcome analysis in
      randomized experiments. This paper describes the potential outcomes framework for
      causal inference and best practices for designing observational studies with
      propensity scores. We discuss the use of propensity scores in two studies
      assessing the effectiveness and risks of antifibrinolytic drugs during cardiac
      surgery.

PMID- 21872982
TI  - Characterization and anti-tumor activity of chemical conjugation of doxorubicin
      in polymeric micelles (DOX-P) in vitro.
AB  - Characterization and anti-tumor activity of chemical conjugation of doxorubicin
      (DOX) in polymeric micelles were investigated. Polymeric micelles with chemical
      conjugation of doxorubicin (DOX-P) were prepared. Succinic anhydride activated
      pluronic F68 was first synthesized and the primary amine group in doxorubicin was
      conjugated to the terminal carboxyl of pluronic F68 via a amide. The resulting
      polymeric micelles in aqueous solution were characterized by measurement of size,
      xi-potential, drug loading and critical micelle concentration. From
      characterization results, DOX-P micelles had superiorities over physically-loaded
      DOX micelles in loading efficiency, diameter and CMC value. From drug release
      experiment in vitro, DOX-P micelles reached a sustained release profile for DOX.
      The cytotoxic activity of the micelles against A549/DOX cells was greater than
      free DOX. Fluorescence microscope observation and flow cytometry analysis
      supported the enhanced cellular uptake of the micelles. From A549/DOX cells
      experiments, DOX-P micelles could enhance DOX anti-tumor activity and circumvent
      the multi-drug resistance (MDR) of A549/DOX cells. With low CMC value, high
      loading efficiency, nanometer diameter, good penetration ability and controlled
      release behaviour, DOX-P micelles might be developed as a new cancer targeted
      delivery system.

PMID- 21872983
TI  - Modeling and simulations of the removal of formaldehyde using silver nano
      particles attached to granular activated carbon.
AB  - A combined reaction, consisting of granular activated carbon (GAC) adsorption and
      catalytic oxidation, has been proposed to improve the removal efficiencies of
      formaldehyde, one of the major indoor air pollutants. In this study, silver nano
      particles attached onto the surface of GAC (Ag-GAC) using the sputtering method
      were evaluated for the simultaneous catalytic oxidation and adsorption of
      formaldehyde. The evolution of CO(2) from the silver nano-particles indicated
      that formaldehyde was catalytically oxidized to its final product, with the
      oxidation kinetics expressed as pseudo-first order. In addition, a packed column
      test showed that the mass of formaldehyde removed by the Ag-GAC was 2.4 times
      higher than that by the virgin GAC at a gas retention time of 0.5s. However, a
      BET analysis showed that the available surface area and micro-pore volume of the
      Ag-GAC were substantially decreased due to the deposition of the silver nano
      particles. To simulate the performance of the Ag-GAC, the homogeneous surface
      diffusion model (HSDM), developed for the prediction of the GAC column
      adsorption, was modified to incorporate the catalytic oxidation taking place on
      the Ag-GAC surface. The modified HSDM demonstrated that numerical simulations
      were consistent with the experimental data collected from the Ag-GAC column
      tests. The model predictions implied that the silver nano-particles deposited on
      the GAC reduced the adsorptive capacity due to decreasing the available surface
      for the diffusion of formaldehyde into the GAC, but the overall mass of
      formaldehyde removed by the Ag-GAC was increased due to catalytic oxidation as a
      function of the ratio of the surface coverage by the nano-particles.

PMID- 21872984
TI  - Interaction of carboxymethylchitosan and heavy metals in cement media.
AB  - The performance of an etherified chitosan, carboxymethylchitosan (CMCH), when
      added to cement mortars doped with heavy metals, was assessed. In the presence of
      heavy metals (Cr, Pb, Zn) strong modifications of the fresh-state properties were
      evaluated. The addition of the polymer was seen to be useful in minimising some
      of these modifications, as those related to the setting time. A competitive
      mechanism for adsorption between the oxoanionic form of the metals and the
      carboxylate groups of the chitosan derivative was established. Studies on the
      metal chelating ability of the polymer and leaching from the hardened specimens
      showed scarce complexation under alkaline conditions, pointing to physical
      entrapment based on metal adsorption. However, significant chelation of metals
      was proved at near-neutral pH, suggesting the potential usefulness of the polymer
      as an agent for removing heavy metals from polluted waters and subsequently
      immobilizing them in cement mortars. Leaching tests carried out on polymer-metal
      complex-bearing samples showed a reduction in the amount of released Pb and Zn.

PMID- 21872985
TI  - Preparation of fluorescent nanofibrous film as a sensing material and adsorbent
      for Cu2+ in aqueous solution via copolymerization and electrospinning.
AB  - Novel naphthalimide-functionalized nanofibrous film was prepared by
      copolymerization and electrospinning. Vinyl naphthalimide monomer was synthesized
      and then copolymerized with methyl methacrylate via solution polymerization. This
      prepared copolymer was electrospun into nanofibrous film, which is an excellent
      sensing material and adsorbent for Cu(2+). When the nanofibrous film was added
      into acetonitrile/aqueous solution, the presence of Cu(2+) induces the formation
      of a 1:1 metal-ligand complex, which exhibits a 48 nm blue-shifted from 487 nm to
      439 nm in fluorescence spectra. The fluorescent film shows high sensitivities due
      to the high surface area-to-volume ratio of the nanofibrous film structures. The
      detection limit for Cu(2+) is 20 * 10(-6)M. Furthermore, the prepared materials
      could be utilized as an adsorbent to remove Cu(2+) in aqueous solution
      efficiently, the adsorption capacity was 10.39 mg of Cu(2+) ions per gram of
      nanofibrous film. All of the results in this paper show that the naphthalimide
      functionalized nanofibrous film made by electrospun technique has excellent
      sensitivities and adsorbent properties toward Cu(2+) over other metal ions.

PMID- 21872986
TI  - Mitochondria as target of quantum dots toxicity.
AB  - Quantum dots (QDs) hold great promise in many biological applications, with the
      persistence of safety concerns about the environment and human health. The
      present work investigated the potential toxicity of CdTe QDs on the function of
      mitochondria isolated from rat livers by examining mitochondrial respiration,
      swelling, and lipid peroxidation. We observed that QDs can significantly affect
      the mitochondrial membrane properties, bioenergetics and induce mitochondrial
      permeability transition (MPT). These results will help us learn more about QDs
      toxicity at subcellular (mitochondrial) level.

PMID- 21872987
TI  - De-mercurization of wastewater by Bacillus cereus (JUBT1): growth kinetics,
      biofilm reactor study and field emission scanning electron microscopic analysis.
AB  - Removal of mercuric ions by a mercury resistant bacteria, called Bacillus cereus
      (JUBT1), isolated from the sludge of a local chlor-alkali industry, has been
      investigated. Growth kinetics of the bacteria have been determined. A
      multiplicative, non-competitive relationship between sucrose and mercury ions has
      been observed with respect to bacterial growth. A combination of biofilm reactor,
      using attached growth of Bacillus cereus (JUBT1) on rice husk packing, and an
      activated carbon filter has been able to ensure the removal of mercury up to near
      zero level. Energy dispersive spectrometry analysis of biofilm and the activated
      carbon has proved the transformation of Hg(2+) to Hg(0) and its confinement in
      the system.

PMID- 21872988
TI  - Catalytic hydrodechlorination of chloroaromatic gas streams promoted by Pd and
      Ni: the role of hydrogen spillover.
AB  - Catalytic hydrodechlorination (HDC) is an effective means of detoxifying
      chlorinated waste. Involvement of spillover hydrogen is examined in gas phase
      dechlorination of chlorobenzene (CB) and 1,3-dichlorobenzene (1,3-DCB) over Pd
      and Ni. The catalytic action of single component Pd and Ni, Pd/Al(2)O(3),
      Ni/Al(2)O(3) and physical mixtures with Al(2)O(3) has been considered. Catalyst
      activation is characterized in terms of temperature programmed reduction, the
      supported nano-scale metal phase by transmission electron microscopy and
      hydrogen/surface interactions by chemisorption/temperature programmed desorption.
      Pd/Al(2)O(3) generated significantly greater amounts of spillover hydrogen (by a
      factor of over 40) compared with Ni/Al(2)O(3). Hydrogen spillover on Pd/Al(2)O(3)
      far exceeded the chemisorbed component, whereas chemisorbed and spillover content
      was equivalent for Ni/Al(2)O(3). Inclusion of Al(2)O(3) with Ni and Ni/Al(2)O(3)
      increased spillover with an associated increase in specific HDC rate (up to a
      factor of 10) and enhanced selectivity to benzene from 1,3-DCB. HDC rate
      delivered by Pd and Pd/Al(2)O(3) was largely unaffected by the addition of
      Al(2)O(3). This can be attributed to the higher intrinsic HDC performance of Pd
      that results in appreciable HDC activity under conditions where Ni/Al(2)O(3) was
      inactive. Spillover was partially recovered (post TPD) for the Ni samples but the
      loss was irreversible in the case of Pd.

PMID- 21872989
TI  - Using cheminformatics to find simulants for chemical warfare agents.
AB  - Direct experimentation with chemical warfare agents (CWA) to study important
      problems such as their permeation across protective barrier materials,
      decontamination of equipment and facilities, or the environmental transport and
      fate of CWAs is not feasible because of the obvious toxicity of the CWAs and
      associated restrictions on their laboratory use. The common practice is to use
      "simulants," namely, analogous chemicals that closely resemble the CWAs but are
      less toxic, with the expectation that the results attained for simulants can be
      correlated to how the CWAs would perform. Simulants have been traditionally
      chosen by experts, by means of intuition, using similarity in one or more
      physical properties (such as vapor pressure or aqueous solubility) or in the
      molecular structural features (such as functional groups) between the stimulant
      and the CWA. This work is designed to automate the simulant identification
      process backed by quantitative metrics, by means of chemical similarity search
      software routinely used in pharmaceutical drug discovery. The question addressed
      here is: By the metrics of such software, how similar are traditional simulants
      to CWAs? That is, what is the numerical "distance" between each CWA and its
      customary simulants in the quantitative space of molecular descriptors? The
      answers show promise for finding close but less toxic simulants for the ever
      increasing numbers of CWAs objectively and fast.

PMID- 21872990
TI  - Waste oil shale ash as a novel source of calcium for precipitated calcium
      carbonate: carbonation mechanism, modeling, and product characterization.
AB  - In this paper, a method for converting lime-containing oil shale waste ash into
      precipitated calcium carbonate (PCC), a valuable commodity is elucidated. The
      mechanism of ash leachates carbonation was experimentally investigated in a
      stirred semi-batch barboter-type reactor by varying the CO(2) partial pressure,
      gas flow rate, and agitation intensity. A consistent set of model equations and
      physical-chemical parameters is proposed to describe the CaCO(3) precipitation
      process from oil shale ash leachates of complex composition. The model enables
      the simulation of reactive species (Ca(2+), CaCO(3), SO(4)(2-), CaSO(4), OH(-),
      CO(2), HCO(3)(-), H(+), CO(3)(2-)) concentration profiles in the liquid, gas, and
      solid phases as well as prediction of the PCC formation rate. The presence of
      CaSO(4) in the product may also be evaluated and used to assess the purity of the
      PCC product. A detailed characterization of the PCC precipitates crystallized
      from oil shale ash leachates is also provided. High brightness PCC (containing up
      to ~ 96% CaCO(3)) with mean particle sizes ranging from 4 to 10 MUm and
      controllable morphology (such as rhombohedral calcite or coexisting calcite and
      spherical vaterite phases) was obtained under the conditions studied.

PMID- 21872991
TI  - Inoculation of endophytic bacteria on host and non-host plants--effects on plant
      growth and Ni uptake.
AB  - Among a collection of Ni resistant endophytes isolated from the tissues of
      Alyssum serpyllifolium, four plant growth promoting endophytic bacteria (PGPE)
      were selected based on their ability to promote seedling growth in roll towel
      assay. Further, the PGPE screened showed the potential to produce plant growth
      promoting (PGP) substances and plant polymer hydrolyzing enzymes. These isolates
      were further screened for their PGP activity on A. serpyllifolium and Brassica
      juncea under Ni stress using a phytagar assay. None of the four isolates produced
      any disease symptoms in either plant. Further, strain A3R3 induced a maximum
      increase in biomass and Ni content of plants. Based on the PGP potential in
      phytagar assay, strain A3R3 was chosen for studying its PGP effect on A.
      serpyllifolium and B. juncea in Ni contaminated soil. Inoculation with A3R3
      significantly increased the biomass (B. juncea) and Ni content (A.
      serpyllifolium) of plants grown in Ni contaminated soil. The strain also showed
      high level of colonization in tissue interior of both plants. By 16S rRNA gene
      sequencing analysis, A3R3 was identified as Pseudomonas sp. Successful
      colonization and subsequent PGP potentiality of Pseudomonas sp. A3R3 indicate
      that the inoculation with PGPE might have significant potential to improve heavy
      metal phytoremediation.

PMID- 21872992
TI  - Genotype-selective phenotypic switch in primary afferent neurons contributes to
      neuropathic pain.
AB  - Pain is normally mediated by nociceptive Adelta and C fibers, while Abeta fibers
      signal touch. However, after nerve injury, Abeta fibers may signal pain. Using a
      genetic model, we tested the hypothesis that phenotypic switching in
      neurotransmitters expressed by Abeta afferents might account for heritable
      differences in neuropathic pain behavior. The study examined selection-line rats
      in which one line, high autotomy (HA), shows higher levels of spontaneous pain in
      the neuroma neuropathy model, and of tactile allodynia in the spinal nerve
      ligation (SNL) model, than the companion low autotomy (LA) line. Changes in
      calcitonin gene-related peptide (CGRP) and Substance P expression were evaluated
      immunohistochemically in L4 and L5 dorsal root ganglia 7 days after SNL surgery.
      Expression of CGRP was decreased in axotomized small- and medium-diameter neurons
      in both rat lines. However, in HA but not in LA rats, there was a tenfold
      increase in CGRP immunoreactivity (CGRP-IR) in large-diameter neurons.
      Corresponding changes in CGRP-IR in axon terminals in the nucleus gracilis were
      also seen. Finally, there were indications of enhanced CGRP neurotransmission in
      deep laminae of the dorsal horn. Substance P immunoreactivity was also
      upregulated in large-diameter neurons, but this change was similar in the 2
      lines. Our findings suggest that phenotypic switching contributes to the
      heritable difference in pain behavior in HA vs LA rats. Specifically, we propose
      that in HA rats, but less so in LA rats, injured, spontaneously active Abeta
      afferents both directly drive CGRP-sensitive central nervous system pain
      signaling neurons and also trigger and maintain central sensitization, hence
      generating spontaneous pain and tactile allodynia.

PMID- 21872993
TI  - Factors contributing to physical activity in a chronic low back pain clinical
      sample: a comprehensive analysis using continuous ambulatory monitoring.
AB  - Back pain is one of the most common causes of disability in industrialized
      nations. Despite this, the variables that contribute to disability are not well
      understood and optimal measurement strategies of disability have not yet been
      determined. The present study sought to comprehensively assess the strongest
      predictors of physical activity as a proxy for disability. New patients in a
      chronic pain specialty clinic completed questionnaires to assess the predictors
      of physical activity and engaged in 5 days of home data collection wearing an
      accelerometer to assess physical activity in daily life, which is how disability
      was operationalized in this study. Analysis of repeated measures patient data
      revealed that, of 3 composite variables each representing a theoretical model,
      the model representative of operant factors significantly predicted physical
      activity. Subsequent analyses showed that pain sensitivity, fear avoidance, and
      solicitous spousal responses account for a significant amount of the variance in
      physical activity. These findings suggest that external sources of reinforcement
      or punishment may serve to influence physical behavior beyond that of internal
      cues such as fear avoidance or pain. Implications for treatment are discussed,
      including the potential benefits of specifically incorporating the patient's
      sources of operant reinforcement or punishment into treatment.

PMID- 21872994
TI  - Acetylcholinesterase of Stomoxys calcitrans (L.) (Diptera: Muscidae): cDNA
      sequence, baculovirus expression, and biochemical properties.
AB  - A 2193-nucleotide cDNA encoding acetylcholinesterase (AChE) of the stable fly,
      Stomoxys calcitrans (L.) was sequenced and expressed in the baculovirus system.
      The open reading frame encoded a 91 amino acid secretion signal peptide and a 613
      amino acid mature protein with 96% and 94% identity to the AChEs of Haematobia
      irritans (L.) and Musca domestica (L.), respectively. Structural characteristics
      of M. domestica, H. irritans, and Drosophila melanogaster AChEs were conserved in
      the S. calcitrans AChE. The recombinant enzyme was inhibited by eserine, coroxon,
      and paraoxon and exhibited K(m) values of 63.9MUM for acetylthiocholine and
      96.7MUM for butyrylthiocholine, confirming its biochemical identity as an
      acetylcholinesterase (EC 3.1.1.7). These data will enable rapid identification
      and assay for mutations that reduce AChE sensitivity to organophosphate (OP)
      pesticides, potentially aiding resistance management efforts to prevent fixation
      of the mutations in pest populations.

PMID- 21872995
TI  - The anthelmintic effect of plant extracts on Haemonchus contortus and
      Strongyloides venezuelensis.
AB  - The indiscriminate use of anthelmintics has resulted in the establishment of
      parasite resistance. Thus, this study aimed to evaluate the in vitro
      antiparasitic effect of plant extracts on Haemonchus contortus in sheep and the
      in vivo effect on Strongyloides venezuelensis in Rattus norvegicus. The plant
      extracts from Piper tuberculatum, Lippia sidoides, Mentha piperita, Hura
      crepitans and Carapa guianensis, produced at different research institutions,
      were chemically analyzed and evaluated through the egg hatch test (EHT) and
      larval development test (LDT) in H. contortus. P. tuberculatum (150 and 250 mg
      kg(-1) of body weight) was evaluated for its anthelmintic action on R. norvegicus
      experimentally infected with S. venezuelensis. In the EHT, the LC(50) and LC(90)
      of the extracts were respectively as follows: 0.031 and 0.09 mg mL(-1) for P.
      tuberculatum, 0.04 and 0.13 mg mL(-1) for L. sidoides, 0.037 and 0.10 mg mL(-1)
      for M. piperita, 2.16 and 17.13 mg mL(-1) for H. crepitans and 2.03 * 10(-6) and
      1.22 * 10(-12) mg mL(-1) for C. guianensis. In the LDT, the LC(50) and LC(90)
      were respectively: 0.02 and 0.031 mg mL(-1) for P. tuberculatum, 0.002 and 0.04
      mg mL(-1) for L. sidoides, 0.018 and 0.03 mg mL(-1) for M. piperita, 0.36 and
      0.91 mg mL(-1) for H. crepitans and 17.65 and 1890 mg mL(-1) for C. guianensis.
      The extract of P. tuberculatum showed the following substances: piperamides as
      (Z)-piplartine, (E)-piplartine, 8,9-dihydropiplartine, piperine, 10,11
      dihydropiperine, 5,6 dihydropiperlongumine and pellitorine. The major compounds
      of the oils were thymol (76.6%) for L. sidoides, menthol (27.5%) for M. piperita
      and oleic acid (46.8%) for C. guianensis. Regarding the in vivo test, neither
      dose of P. tuberculatum caused any significant reduction (P>0.05) in worm burden
      and fecal egg counts compared with the control group. We conclude that the
      extracts of P. tuberculatum, L. sidoides and M. piperita have effective activity
      when tested in vitro, but the doses of the extract of P. tuberculatum have no
      effect when employed in in vivo tests.

PMID- 21872996
TI  - Docetaxel combined with targeted therapies in metastatic breast cancer.
AB  - The treatment of metastatic breast cancer (MBC) is essentially palliative and
      should be based on hormone therapy or optimized chemotherapy designed to delay
      disease progression and maximize survival with good quality of life. Novel
      chemotherapeutic agents introduced in the 1990 s include the taxanes (notably
      docetaxel), which are among the most potent of current anticancer drugs. Current
      research is also focusing on molecular targeted agents including those against
      the HER family of transmembrane receptors and vascular endothelial growth factor.
      Optimal effects are obtained when these compounds are used in combination with
      chemotherapy, as shown in preclinical models and more recently in clinical
      trials. Results of a large randomized trial have demonstrated a significant
      survival advantage for trastuzumab plus docetaxel compared with docetaxel
      monotherapy. Docetaxel plus bevacizumab combinations have recently been shown to
      significantly improve progression-free survival and objective response rate
      compared with docetaxel monotherapy. Overall, docetaxel in combination with novel
      targeted agents in MBC appears to be highly active in patients with MBC, and such
      combinations represent promising treatment regimens for clinical investigation.

PMID- 21872998
TI  - Efficacy of a flexible quit date versus an a priori quit date approach to smoking
      cessation: a cross-study analysis.
AB  - Most treatment guidelines recommend that smokers should set a target quit date
      (TQD) at treatment onset because making a public commitment to quit on a given
      date should increase motivation. On the other hand, allowing smokers the
      flexibility to choose when to stop after starting treatment might allow smokers
      to better tailor their quit date and might improve the acceptability of treatment
      among smokers not willing to set a TQD. In a recent placebo-controlled study, we
      found varenicline effective when smokers were not required to set a quit date a
      priori; i.e., with a "flexible quit date" (FQD) approach. The current analysis
      compares the effect sizes and quit rates in this FQD study with those of nine
      prior varenicline randomized controlled trials (RCTs) that used a TQD approach.
      The odds ratio for varenicline versus placebo in the FQD study was the 4th
      highest of the 10 trials and the incidence of continuous abstinence for
      varenicline was 5th highest. These results suggest that a FQD approach can
      produce quit rates similar to a TQD approach. Cross-study comparisons can have
      hidden bias; thus, a RCT of fixed versus flexible quit dates would provide a more
      valid test. Also, a study of whether different subpopulations of smokers may be
      more interested in or especially benefit from, one or the other approach to
      quitting is indicated.

PMID- 21872997
TI  - Childhood abuse and harmful substance use among criminal offenders.
AB  - Childhood abuse is a serious problem that has been linked to harmful alcohol and
      drug use in non-offender samples. In a sample of 219 criminal offenders, we
      examined the associations between childhood physical and sexual abuse and three
      indices of harmful substance use. Results indicate that physical abuse was
      associated with symptoms of alcohol use disorder and sexual abuse was associated
      with symptoms of drug use disorder among offenders. Both forms of childhood abuse
      were associated with substance use consequences, even after taking into account
      substance type and frequency of use. No gender by childhood abuse interactions
      were found. Symptoms of depression and generalized anxiety partially mediated
      relationships between childhood abuse and substance use consequences. Findings
      underscore the importance of assessing childhood abuse and treating anxiety and
      depression among offenders who exhibit harmful substance use.

PMID- 21872999
TI  - A possible mechanism for maintenance of the deleterious allele of human CASPASE
      12.
AB  - In humans, a functional CASPASE-12 (CASP12) gene has been identified only in
      persons of African heritage and has been suggested to play a regulatory role in
      response to bacterial pathogens and in promoting and increased susceptibility to
      sepsis. The existence of a gene whose effect is deleterious, and which has been
      the subject of extensive negative selection in the rest of the human population,
      implies the simultaneous presence of some selective benefit for persons having
      CASP12. Given the importance of inflammatory immune responses in controlling the
      initial stages of infection, and the role that CASP12 plays in down-regulating
      inflammation, we hypothesize that pathogens which exploit the inflammatory
      response are restrained by an active CASP12 gene product. Several candidate
      pathogens are discussed.

PMID- 21873000
TI  - Decreases in fluid shear stress due to microcracks: a possible primary
      pathogenesis of Kummell's disease.
AB  - The German doctor Hermann Kummell described Kummell's disease as the clinical
      scenario in which patients suffer a trivial spinal trauma, but develop a
      symptomatic, progressive, angular kyphosis after a symptom-free period of months
      to years. Since an intravertebral vacuum phenomenon, which is considered
      indicative of ischemic osteonecrosis, is often seen in the radiographs of
      patients with Kummell's disease, most authors regard ischemic necrosis of the
      vertebral body as the primary pathogenesis of Kummell's disease. However, we
      argue that Kummell's disease is not commonly associated with typical avascular
      osteonecrosis of the femoral head and the intravertebral vacuum phenomenon is
      also present in other diseases. We postulated that even if ischemia plays a role
      in the pathogenesis of Kummell's disease, it would not be the proximal cause of
      Kummell's disease. In this article, we review the role of fluid shear stress in
      bone remolding and propose a microcosmic hypothesis in which microcracks lead to
      decreased fluid shear stress, which acts as the primary cause of Kummell's
      disease. This was supported by conclusions drawn from a literature review: (1)
      fluid shear stress plays a crucial role in bone remodeling, and the osteocyte
      network is the main sensor of this mechanical stimulus; (2) decreased fluid shear
      stress will cause disequilibration of bone homeostasis, increasing bone
      resorption and reducing bone formation; and (3) the fluid flow of lacunar
      canalicular porosity (PLC) and fluid shear stress near the microcracks decreases.

PMID- 21873001
TI  - Effect of whole linseed addition on meat production and quality of Italian
      Simmental and Holstein young bulls.
AB  - The effect of long term dietary linseed addition on performance, carcass
      characteristics and meat quality of Italian Simmental (IS) and Italian Holstein
      (HI) young bulls was investigated. Thirty-two animals were assigned to 4 groups
      following a factorial design: 2 breeds - IS and IH - *2 diets - containing whole
      ground linseed (5-8% of DM) and control. IS had greater in vivo performance and
      carcass characteristics than IH. IS muscle had lower C14:0, C16:0, SFA, higher
      C18:2n-6 cis, PUFAn-6, PUFA and PUFA/SFA proportion than IH in phospholipids (PL)
      fraction. Linseed inclusion did not affect animal's performance and carcass
      characteristics. In muscle PL, linseed increased C20:0, C22:0, C23:0, C20:5n-3
      and decreased C20:4n-6, PUFAn-6/n-3, PUFAn-6 concentration. Linseed decreased
      C14:0, C16:0 proportion in neutral lipids (NL) and increased total PUFAn-3,
      C18:3n-3 proportions both in NL and PL fraction. However, these differences were
      relatively low from a quantitative point of view.

PMID- 21873002
TI  - Repair of flexor digitorum profundus to distal phalanx: a biomechanical
      evaluation of four techniques.
AB  - PURPOSE: Many techniques for repair of the flexor digitorum profundus to the
      distal phalanx show excessive gapping with variable clinical results. The purpose
      of this study was to test the biomechanical characteristics of an anchor-button
      (AB) technique, as compared to 3 other techniques. METHODS: Twenty-four fresh
      frozen human cadaveric fingers were randomized to 4 groups, 6 in each: group 1, 2
      strand Bunnell suture button pullout technique; group 2, modified Kessler suture
      and 2 retrograde anchors; group 3: locking Krakow suture with 2 retrograde
      anchors; group 4, AB technique incorporating a 2-part repair, consisting of a
      locking dorsal Krakow suture with 2 retrograde anchors and a locking palmar
      Krakow suture fixed with a button. Tendon-to-bone gapping was measured after
      cyclical loading. Ultimate load to failure was measured at the end of 500 cycles.
      RESULTS: The AB technique resulted in significantly less gapping when compared to
      the other techniques. It also resulted in a significantly stronger repair
      compared to all the other groups with an average load to failure comparable to
      the native tendon-to-bone interface. CONCLUSIONS: The AB repair might allow for
      early active postoperative motion after repair of flexor digitorum profundus
      avulsion injuries and tendon reconstruction procedures; however, the soft tissue
      effects of this multistrand technique are unknown in clinical repairs.

PMID- 21873003
TI  - Bilateral avascular necrosis of the trapezoid.
AB  - We present a 5-year follow-up of a patient with bilateral necrosis of the
      trapezoid that improved clinically and radiographically with nonoperative
      treatment.

PMID- 21873004
TI  - Capsulectomy and debridement for primary osteoarthritis of the elbow through a
      medial trans-flexor approach.
AB  - PURPOSE: Debridement arthroplasty combined with capsulectomy for primary
      osteoarthritis of the elbow is a useful procedure to relieve pain and increase
      mobility. We have used a medial trans-flexor approach without tendon detachment
      for debridement arthroplasty of the elbow and evaluated the outcome of this
      procedure. METHODS: Thirty-one elbows with primary osteoarthritis in 31 patients
      treated with debridement arthroplasty were available for follow-up at a mean of
      19 +/- 7 months. Twenty-four patients were men, and 7 were women. The mean age at
      the time of surgery was 59 +/- 10 years. All elbows were painful only at the end
      points of motion. The anterior compartment of the elbow was accessed by splitting
      of the pronator flexor muscle group without tendon detachment. Routine anterior
      subcutaneous transposition of the ulnar nerve was used in all elbows. In 10
      elbows, osteophytes or loose osseous bodies from the lateral compartment were
      removed through an additional lateral approach. RESULTS: Twenty-three elbows had
      no pain, and 8 elbows had mild pain. The mean preoperative limitation of
      extension decreased from 29 degrees  +/- 9 degrees  to 15 degrees  +/- 9 degrees 
      and the mean preoperative flexion increased from 100 degrees  +/- 10 degrees  to
      126 degrees  +/- 7 degrees . Thus, the mean arc of elbow motion increased by 40
      degrees  +/- 13 degrees . The mean Mayo Elbow Performance Score was 94 +/- 7
      compared with 60 +/- 5 before surgery. The results were excellent for 22 elbows
      and good for 9. Hematomas developed in 3 elbows, but they did not require
      surgical drainage. CONCLUSIONS: Debridement arthroplasty using the medial trans
      flexor approach without tendon detachment yields satisfactory short-term clinical
      results. This approach is associated with a low rate of complications and is safe
      and effective for the treatment of primary osteoarthritis of the elbow. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 21873005
TI  - Cosmetic concerns and management strategies to combat aging.
AB  - Multiple modalities with varying degrees of complexity and risks exist in the
      treatment of the aging face. Paramount to all treatment paradigms is
      photoprotection to prevent further damage. Intervetions should be geared towards
      addressing the intrinsic and extrinsic signs of aging and can include topical
      retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and
      soft tissue fillers. The combination of these primary, secondary, and tertiary
      therapies will address the underlying pathophysiologic changes of the aging face
      and thus will provide the optimal aesthetic outcome.

PMID- 21873006
TI  - Detection and validated quantification of 21 benzodiazepines and 3 "z-drugs" in
      human hair by LC-MS/MS.
AB  - A method for detection and quantification of 21 benzodiazepines and the
      pharmacologically related "z-drugs" in human hair samples was developed and fully
      validated using liquid chromatography coupled to tandem mass spectrometry (LC
      MS/MS). After methanolic and methanolic/aqueous extraction, the analytes were
      separated using two different LC-MS systems (AB Sciex 3200 QTRAP and AB Sciex
      5500 QTRAP). Separation columns, mobile phases and MS modes for both systems
      were: Phenomenex Kinetex, 2.6 MUm, 50/2.1; 5mM ammonium formate buffer pH
      3.5/methanol, total flow 0.75 mL/min; electrospray ionization (ESI), multiple
      reaction monitoring (MRM), information dependent acquisition (IDA), enhanced
      product ion scan (EPI). The assays were found to be selective for the tested
      compounds (alprazolam, 7-aminoclonazepam, 7-aminoflunitrazepam, bromazepam,
      chlordiazepoxide, clonazepam, N-desalkylflurazepam, diazepam, flunitrazepam,
      flurazepam, alpha-hydroxymidazolam, lorazepam, lormetazepam, midazolam,
      nitrazepam, nordazepam, oxazepam, phenazepam, prazepam, temazepam, triazolam,
      zaleplon, zolpidem and zopiclone), all validation criteria were in the required
      ranges according to international guidelines, except for bromazepam. Matrix
      effects, and process efficiencies were in the acceptable ranges evaluated using
      the post-extraction addition approach. Lower limits of quantification were
      between 0.6 and 16 pg/mg of hair. The LC-MS/MS assay has proven to be applicable
      for determination of the studied analytes in human hair in numerous authentic
      cases (n=175).

PMID- 21873007
TI  - Determination of hydrogen peroxide concentration using a handheld Raman
      spectrometer: Detection of an explosives precursor.
AB  - It has been shown that a handheld Raman spectrometer can be used to determine
      hydrogen peroxide concentration in aqueous solutions in seconds. To allow
      quantitative analysis, the aqueous peroxide samples were mixed 50/50 (v/v) with a
      4mol/dm(3) sodium perchlorate solution which acted as the internal standard.
      Standard calibration using relative peak heights of the strongest perchlorate
      (932cm(-1)) and peroxide bands (876cm(-1)) gave an average error of 1.43% for
      samples in the range 5-30% peroxide. PLS regression of the same data set gave an
      average error of 0.98%. In addition, the concentrations of the samples were
      estimated by searching spectra against a library of standard spectra prepared
      using the same range of peroxide concentrations at 5% increments and with the
      same perchlorate internal standard. It was found that the library searching
      method classified all the test samples correctly, matching either the spectra of
      the same concentration, if they were present, or matching to the closest
      concentration if an exact match was not possible. This method thus provides a
      very rapid technique to allow determination of hydrogen peroxide concentrations
      in the field, for example at suspected improvised explosives manufacturing sites,
      without complex calibration procedures.

PMID- 21873008
TI  - Serum biochemical markers in drowning: diagnostic efficacy of Strontium and other
      trace elements.
AB  - The aim of our study was to analyse several serum biochemical markers in order to
      evaluate the discriminant capacity of trace elements individually and jointly in
      drowning (seawater drowning and freshwater drowning) and their correlation with
      age, sex, postmortem interval, time in water and concentrations of the trace
      elements in the drowning medium. Sixty-seven cases of drowning (53 seawater
      drownings (SWD); 14 freshwater drownings (FWD) and 73 control cases (other
      asphyxias, n=44, and other causes of death, n=29) were selected according to the
      scene, cause and circumstances of death, together with autopsy findings. Serum
      strontium (Sr), magnesium (Mg), sodium (Na), chloride (Cl), calcium (Ca), iron
      (Fe), urea, creatinine (Cr) and cardiac Troponine T (cTn-T) were measured in the
      left ventricle (Lv), right ventricle (Rv) and peripheral blood. Lv-Rv differences
      for each marker and Sr, Mg, Na, Cl, Ca and Fe concentrations in the drowning
      medium were determinated. Mean concentrations of Sr, Cl and Mg in both ventricles
      and peripheral serum and Lv-Rv differences and Ca Lv and Na Rv were significantly
      higher in cases of drowning than for other causes of death. In SWD, Sr, Mg, Ca,
      Na and Cl were significantly higher in Lv than in Rv as a result of aspirating
      water. In contrast, haemodilution is evident from the significantly higher levels
      of Fe and urea in Rv than in Lv in cases of SWD, and from the higher Mg and Cr
      levels in Rv in FWD. In the case of SWD, serum levels of Sr are confirmed as the
      best parameter for diagnosis, although other trace elements may also be useful,
      such as the serum concentrations of Mg and Cl. In the case of FWD, the joint
      determination of Sr and other biochemical markers, especially Fe, may increase
      correct diagnosis.

PMID- 21873009
TI  - Evaluation of an electronic comparison system and implementation of a
      quantitative effectiveness criterion.
AB  - The identification of fired bullets and spent cartridge cases is one of the key
      tasks of forensic science. The traditional comparison of signatures on specimen
      with a large collection with only a microscope is a very tedious and time
      consuming work. Fortunately, electronic systems for performing a pre-selection
      have been invented since the last 25 years. On the basis of an expansive database
      the electronic comparison system used by the BKA, Germany, is evaluated and a
      mathematical value is proposed to rate the correlation quality. This
      effectiveness criterion can be valuable to give an objective assessment of
      different electronic comparison systems. Additionally, the applicability of the
      system on different calibres and land engraved area (LEA) width is discussed. The
      so called scores are also on disposition and their benefit to a decision-making
      is debated.

PMID- 21873010
TI  - Extraosseous osteosarcoma in the neck.
AB  - BACKGROUND: Extraosseous osteosarcoma arising in the head and neck region is an
      exceptional finding, with a few isolated cases informed in the literature. We
      report a new case of a large high-grade extraosseous osteosarcoma located in the
      neck. CASE PRESENTATION: A 74 year-old woman with a tumor on the right side of
      the neck was treated by complete surgical resection. The histopathological
      diagnosis was osteoblastic extraosseous osteosarcoma. PET-CT scan disclosed no
      evidence of disease in other areas. Patient received adjuvant radiotherapy and
      after 3 months of follow-up tumor activity was detected in the cavernous sinus
      and the patient died of disease one month later. CONCLUSION: Extraosseous
      osteosarcoma in head and neck region is exceptional, and incisional biopsy is the
      only method to establish a diagnosis and the one to differentiate it from other
      bone-producing soft tissue tumors. Surgery is the gold standard for treatment of
      extraosseous osteosarcoma.

PMID- 21873011
TI  - A joint shape evolution approach to medical image segmentation using expectation
      maximization algorithm.
AB  - This study proposes an expectation-maximization (EM)-based curve evolution
      algorithm for segmentation of magnetic resonance brain images. In the proposed
      algorithm, the evolution curve is constrained not only by a shape-based
      statistical model but also by a hidden variable model from image observation. The
      hidden variable model herein is defined by the local voxel labeling, which is
      unknown and estimated by the expected likelihood function derived from the image
      data and prior anatomical knowledge. In the M-step, the shapes of the structures
      are estimated jointly by encoding the hidden variable model and the statistical
      prior model obtained from the training stage. In the E-step, the expected
      observation likelihood and the prior distribution of the hidden variables are
      estimated. In experiments, the proposed automatic segmentation algorithm is
      applied to multiple gray nuclei structures such as caudate, putamens and thalamus
      of three-dimensional magnetic resonance imaging in volunteers and patients. As
      for the robustness and accuracy of the segmentation algorithm, the results of the
      proposed EM-joint shape-based algorithm outperformed those obtained using the
      statistical shape model-based techniques in the same framework and a current
      state-of-the-art region competition level set method.

PMID- 21873012
TI  - Evaluation of diffusion models of fiber tracts using diffusion tensor magnetic
      resonance imaging.
AB  - Modeling of water diffusion in white matter is useful for revealing
      microstructure of the brain tissue and hence diagnosis and evaluation of white
      matter diseases. Researchers have modeled diffusion in white matter using
      mathematical and mechanical analysis at the cellular level. However, less work
      has been devoted to evaluate these models using macroscopic real data such as
      diffusion tensor magnetic resonance imaging (DTMRI) data. DTMRI is a noninvasive
      tool for evaluating white matter microstructure by measuring random motion of
      water molecules referred to as diffusion. It reflects directional information of
      microscopic structures such as fibers. Thus, it is applicable for evaluation and
      modification of mathematical models of white matter. Nevertheless, a realistic
      relation between a fiber model and imaging data does not exist. This work opens a
      promising avenue for relating DTMRI data to microstructural parameters of white
      matter. First, we propose a strategy for relating DTMRI and fiber model
      parameters to evaluate mathematical models in light of real data. The proposed
      strategy is then applied to evaluate and extend an existing model of white matter
      based on clinically available DTMRI data. Next, the proposed strategy is used to
      estimate microstructural characteristics of fiber tracts. We illustrate this
      approach through its application to approximation of myelin sheath thickness and
      fraction of volume occupied by fibers. Using sufficiently small imaging voxels,
      the proposed approach is capable of estimating model parameters with desirable
      precision.

PMID- 21873013
TI  - Data fusion of Fourier transform infrared spectra and powder X-ray diffraction
      patterns for pharmaceutical mixtures.
AB  - Fusing complex data from two disparate sources has been demonstrated to improve
      the accuracy in quantifying active ingredients in mixtures of pharmaceutical
      powders. A four-component simplex-centroid design was used to prepare blended
      powder mixtures of acetaminophen, caffeine, aspirin and ibuprofen. The blends
      were analyzed by Fourier transform infra-red spectroscopy (FTIR) and powder X-ray
      diffraction (PXRD). The FTIR and PXRD data were preprocessed and combined using
      two different data fusion methods: fusion of preprocessed data (FPD) and fusion
      of principal component scores (FPCS). A partial least square (PLS) model built on
      the FPD did not improve the root mean square error of prediction. However, a PLS
      model built on the FPCS yielded better accuracy prediction than PLS models built
      on individual FTIR and PXRD data sets. The improvement in prediction accuracy of
      the FPCS may be attributed to the removal of noise and data reduction associated
      with using PCA as a preprocessing tool. The present approach demonstrates the
      usefulness of data fusion for the information management of large data sets from
      disparate sources.

PMID- 21873014
TI  - Stability-indicating micellar electrokinetic chromatography method for the
      analysis of sumatriptan succinate in pharmaceutical formulations.
AB  - A micellar electrokinetic chromatography method for the determination of
      sumatriptan succinate in pharmaceutical formulations was developed. The effects
      of several factors such as pH, surfactant and buffer concentration, applied
      voltage, capillary temperature, and injection time were investigated. Separation
      took about 5 min using phenobarbital as internal standard. The separation was
      carried out in reversed polarity mode at 20  degrees C, 26 kV and using
      hydrodynamic injection for 10s. Separation was achieved using a bare fused-silica
      capillary 50 MUm*40 cm and background electrolyte of 25 mM sodium dihydrogen
      phosphate-adjusted with concentrated phosphoric acid to pH 2.2, containing 125 mM
      sodium dodecyl sulfate and detection was at 226 nm. The method was validated with
      respect to linearity, limits of detection and quantification, accuracy, precision
      and selectivity. The calibration curve was linear over the range of 100-2000 MUg
      mL(-1). The relative standard deviations of intra-day and inter-day precision for
      migration time, peak area, corrected peak area, ratio of corrected peak area and
      ratio of peak area were less than 0.68, 3.48, 3.28, 2.97 and 2.83% and 2.01,
      5.50, 4.46, 4.92 and 4.07%, respectively. The proposed method was successfully
      applied to the determinations of the analyte in tablet. Forced degradation
      studies were conducted by introducing a sample of sumatriptan succinate standard
      solution to different forced degradation conditions using neutral (water), basic
      (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H(2)O(2)) and photolytic
      (exposure to UV light at 254 nm for 2 h). It is concluded that the stability
      indicating method for sumatriptan succinate can be used for the analysis of the
      drug in various samples.

PMID- 21873015
TI  - Critical assessment of accelerating trypsination methods.
AB  - In LC-MS based proteomics, several accelerating trypsination methods have been
      introduced in order to speed up the protein digestion, which is often considered
      a bottleneck. Traditionally and most commonly, due to sample heterogeneity,
      overnight digestion at 37  degrees C is performed in order to digest both easily
      and more resistant proteins. High efficiency protein identification is important
      in proteomics, hours with LC-MS/MS analysis is needless if the majority of the
      proteins are not digested. Based on preliminary experiments utilizing some of the
      suggested accelerating methods, the question of whether accelerating digestion
      methods really provide the same protein identification efficiency as the
      overnight digestion was asked. In the present study we have evaluated four
      different accelerating trypsination methods (infrared (IR) and microwave
      assisted, solvent aided and immobilized trypsination). The methods were compared
      with conventional digestion at 37  degrees C in the same time range using a four
      protein mixture. Sequence coverage and peak area of intact proteins were used for
      the comparison. The accelerating methods were able to digest the proteins, but
      none of the methods appeared to be more efficient than the conventional digestion
      method at 37  degrees C. The conventional method at 37  degrees C is easy to
      perform using commercially available instrumentation and appears to be the
      digestion method to use. The digestion time in targeted proteomics can be
      optimized for each protein, while in comprehensive proteomics the digestion time
      should be extended due to sample heterogeneity and influence of other proteins
      present. Recommendations regarding optimizing and evaluating the tryptic
      digestion for both targeted and comprehensive proteomics are given, and a
      digestion method suitable as the first method for newcomers in comprehensive
      proteomics is suggested.

PMID- 21873016
TI  - Identification and determination of the major constituents in Deng's herbal tea
      granules by rapid resolution liquid chromatography coupled with mass
      spectrometry.
AB  - Deng's herbal tea (DHT), a famous traditional Chinese herbal tea consisting of
      six traditional Chinese medicines (Honeysuckle, Chrysanthemum, Rhizoma imperatae,
      Folium mori, dandelion and liquorice), is widely used in China for its health
      benefits. In this paper, a rapid resolution liquid chromatography coupled with
      mass spectrometry (RRLC-MS) method was developed for the identification and
      determination of the major constituents in DHT granules. A good RRLC separation
      was achieved using an Agilent Poroshell 120 SB-C(18) column and gradient elution
      (0.5% formic acid in water/acetonitrile) within 30 min. Twenty-eight compounds
      were identified or tentatively characterized based on their exact molecular
      weights and fragmentation patterns. Fifteen major bioactive constituents of those
      28 compounds were chosen as the benchmark substances. Their quantitative analyses
      were performed by a triple quadrupole tandem mass spectrometer (MS/MS) operating
      in multiple-reaction monitoring mode, and a full quantitative analysis of the 15
      major constituents was performed by our developed RRLC-MS/MS method in only 10
      min. Of the 16 DHT granule samples tested, the quality of the results was stable,
      which confirms that the developed method was efficient and robust for the quality
      control of DHT granules.

PMID- 21873017
TI  - Demonstration that methadone is being present in the exhaled breath aerosol
      fraction.
AB  - Methadone has previously been found present in exhaled breath of methadone
      treated patients. This study aimed at studying if methadone is present in the
      aerosol fraction of exhaled breath and used different filter sampling techniques
      for that. Patients receiving methadone maintenance treatment were recruited for
      the study. Methadone was extracted from filters collecting methadone from exhaled
      breath using 2-propanol, methanol and ethyl acetate and measured using liquid
      chromatography-tandem mass-spectrometry. The limit of quantification was 5
      pg/sample and the intra-day imprecision and accuracy within 15%. The recovery of
      extracting methadone from filters was >90%. Two types of micro-particle filters
      were used in this study and were compared with the C18 silica filter (Empore)
      used before. The Glass fiber filter collected methadone from exhaled breath of
      methadone patients. The amount collected significantly exceeded the amount using
      the C18 Empore filter (3.6-14-fold), but the variability of amount trapped was
      large. The second filter type was a polymer filter. Also this filter was able to
      trap methadone from exhaled breath of methadone patients. The amount and
      variability was similar to the C18 Empore filter but smaller than the Glass fiber
      filter. The mean rate of methadone excretion measured with the best polymer
      filter was 92 pg/min with a range between 20 and 287 (n=5). The polymer filter
      has the practical advantage of having a low flow resistance making it possible to
      sample without pumping assistance. The polymer filter was found to collect >90%
      of the exhaled methadone. The conclusion of this study was that methadone in
      exhaled breath is carried in the aerosol fraction known to be formed in the lung
      as a result of normal breathing.

PMID- 21873018
TI  - Motivational interviewing and shared decision making in primary care.
AB  - OBJECTIVE: The aim of this study was to assess general practitioners' (GP)
      readiness to involve obese patients in therapy decision making and to determine
      whether they integrate motivational interviewing techniques. METHODS: Fifty-eight
      preventive Check-up 35 encounters with overweight and obese patients in primary
      care were audio recorded in 12 GP practices. The use of motivational interviewing
      techniques was rated with the Behavior Change Counseling Index (BECCI). The
      involvement in medical decisions was rated with the Observing Patient Involvement
      Scale (OPTION). RESULTS: OPTION and BECCI scores were low (means=0.71 and 1.65),
      indicating minimal implementation of shared decision making and motivational
      interviewing in preventive encounters with these patients. GPs used more
      motivational interviewing for patients with a BMI>30 kg/m(2) than for those with
      a BMI<30 kg/m(2). Female GPs had significantly higher shared decision making
      scores, indicating that they prefer to involve patients in medical decisions. GPs
      differed significantly in their use of both approaches. CONCLUSIONS: Shared
      decision making and motivational interviewing, though known to be successful
      strategies in lifestyle counseling, are rarely used during obesity encounters in
      our sample of German GPs. PRACTICE IMPLICATIONS: GPs should be sensitized and
      trained in the application of these methods.

PMID- 21873019
TI  - Aortic type B dissection with acute expansion of iliac artery aneurysm in
      previous endovascular repair with iliac branched graft.
AB  - We report the case of a patient previously treated with an iliac branch endograft
      for isolated iliac artery aneurysm who developed, more than 2 years later, a type
      B aortic dissection resulting in the acute expansion of the previously excluded
      iliac aneurysm. Successful endovascular salvage is described.

PMID- 21873020
TI  - Posteromedial elbow impingement: magnetic resonance imaging findings in overhead
      throwing athletes and results of arthroscopic treatment.
AB  - PURPOSE: The purpose of this study was to define the magnetic resonance imaging
      (MRI) pattern and assess the results of arthroscopic treatment of posteromedial
      elbow impingement in overhead throwers. METHODS: Over an 8-year period, 9
      throwing athletes diagnosed with posteromedial elbow impingement were
      retrospectively identified. All patients had either a noncontrast or direct
      arthrogram-MRI study that was reviewed by a single, fellowship-trained
      musculoskeletal radiologist blinded to the clinical diagnosis. Arthroscopic
      treatment included debridement of posteromedial synovitis, loose body removal,
      and excision of the olecranon spur. All patients underwent a physical examination
      and completion of the Andrews-Carson scale at a mean of 68 months (range, 25 to
      112 months). RESULTS: All patients were male, with a mean age of 21.0 years
      (range, 17 to 34 years). The dominant arm was affected in all patients. The mean
      length of symptoms before surgery was 9 months (range, 5 to 24 months). At MRI, a
      reproducible pattern of pathology was noted. All patients had pathology at the
      articular surfaces of the posterior trochlea and the anterior, medial olecranon.
      The findings ranged from abnormal edema-like signal in the hyaline cartilage to
      cartilage defects and subjacent, subchondral bone marrow edema. Findings at
      surgery included posteromedial synovitis and olecranon spurring in all patients
      and loose bodies in 3 patients. On the basis of the Andrews-Carson scale, the
      subjective and objective outcome was considered excellent in 7 patients and good
      in 2. CONCLUSIONS: Posteromedial elbow impingement is a source of disability in
      the overhead throwing athlete. Correlation of history and physical examination
      with imaging findings is essential to confirm the diagnosis. This study indicates
      that MRI identifies a reproducible pattern of pathology in throwing athletes with
      this disorder. These MRI findings correlate highly with arthroscopic evaluation.
      Arthroscopic debridement, olecranon spur excision, and loose body removal allow
      return to throwing sports and reliable subjective and objective results in
      carefully selected patients.

PMID- 21873021
TI  - Results of arthroscopic decompression and tuberoplasty for irreparable massive
      rotator cuff tears.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and radiologic
      results of arthroscopic tuberoplasty for symptomatic irreparable massive rotator
      cuff tears. METHODS: This study enrolled 32 patients (32 shoulders) who underwent
      arthroscopic tuberoplasty for irreparable massive rotator cuff tears and were
      followed up for at least 24 months. The mean patient age at the time of surgery
      was 62.4 years (range, 43 to 76 years), and the mean duration of follow-up was 40
      months (range, 24 to 63 months). The Constant score and the University of
      California, Los Angeles score were used for clinical evaluation. The
      acromiohumeral interval and inferior scapulohumeral line continuity were used for
      radiologic evaluation. RESULTS: Twenty-six shoulders underwent arthroscopic
      tuberoplasty with concomitant acromioplasty, and 6 shoulders had only
      arthroscopic tuberoplasty. The Constant score increased from a preoperative mean
      of 47.6 points to 70.4 points at the last follow-up (P < .001). The University of
      California, Los Angeles score also improved from a preoperative mean of 15.4
      points to 27.1 points at the last follow-up (P < .001), with 3 shoulders (9%)
      rated as excellent, 23 (72%) as good, and 6 (19%) as poor. The active range of
      forward flexion improved from 115.9 degrees  to 142.7 degrees  (P = .024). The
      final outcomes were not statistically affected by sex, age, preoperative
      mobility, and existence of a lesion of the long head of the biceps tendon.
      However, preoperative acromiohumeral interval and inferior scapulohumeral line
      continuity were statistically correlated with the final results (P < .001 and P =
      .047, respectively). CONCLUSIONS: Arthroscopic tuberoplasty with concomitant
      acromioplasty, as well as treatment of the biceps tendon when indicated, would be
      an option for diminishing pain and improving active forward elevation for
      irreparable massive rotator cuff tears. In particular, satisfactory results
      during the minimum follow-up period of 24 months can be achieved in the cases
      with good preservation of the preoperative and postoperative acromiohumeral
      interval and continuity in the inferior scapulohumeral line, regardless of
      preoperative mobility.

PMID- 21873022
TI  - Splenectomy for an adult patient with refractory secondary hemophagocytic
      lymphohistiocytosis.
AB  - Treatment regimens of secondary hemophagocytic lymphohistiocytosis (sHLH) are
      complicated and individualized. CHOP regimen is well known for the treatment of
      adult sHLH, but it was not so effective for the 56-year-old male patient in our
      study. Splenomegaly, one of clinical manifestations of HLH, has urged us to
      investigate the role of splenectomy in HLH patients. Splenectomy is not only
      beneficial to confirm the underlying diseases, but also beneficial for the
      treatment of HLH. Here, we present a case diagnosed as sHLH who has recovered
      from HLH following comprehensive treatment based on splenectomy. The therapeutic
      value of splenectomy in sHLH needs further study.

PMID- 21873023
TI  - Cross-sectional imaging of small bowel malignancies.
AB  - Small bowel malignancies are rare neoplasms, usually inaccessible to conventional
      endoscopy but detectable in many cases by cross-sectional imaging. Modern
      multidetector computed tomographies permit accurate diagnosis, complete
      pretreatment staging, and follow-up of these lesions. In this review, we describe
      the cross-sectional imaging features of the most frequent histologic subtypes of
      the small bowel malignancies.

PMID- 21873024
TI  - The CanMEDS resume: a useful educational portfolio tool for diagnostic radiology
      residents.

PMID- 21873025
TI  - After-hours radiology consultation in an academic setting, 2005-2009.

PMID- 21873026
TI  - Spatial distribution of corneal light scattering after corneal collagen
      crosslinking.
AB  - PURPOSE: To assess the spatial distribution and time course of increased corneal
      light scattering after corneal collagen crosslinking (CXL) with riboflavin and
      ultraviolet-A irradiation. SETTING: Umea University Hospital Eye Clinic, Umea,
      Sweden. DESIGN: Case series. METHODS: Eyes with keratoconus were examined with
      Scheimpflug photography before and 1 and 6 months after CXL. Corneal light
      scattering was quantified throughout the corneal thickness at 8 measurement
      points 0.0 to 3.0 mm from the central cornea. RESULTS: The study comprised 11
      eyes of 11 patients. Central corneal light scattering increased significantly 1
      month after CXL (P<.001). At 6 months, it decreased (P = .002); however, it was
      still higher than pretreatment values (P<.001). Light scattering at 1 month was
      more pronounced in the superficial stroma, gradually diminishing to zero at 240
      MUm depth. It was greater at the corneal center than 1.0 to 3.0 mm from the
      center. At 6 months, a second peak of light scattering occurred between 240 MUm
      and 340 MUm depth. No increased light scattering deeper than 340 MUm was seen at
      either time point. CONCLUSIONS: Corneal light scattering after CXL showed
      distinctive spatial and temporal profiles. Analysis of corneal light scattering
      may give an impression of tissue changes, the depth of the CXL treatment effect,
      and the corneal response to the treatment. Scheimpflug photography appears to be
      useful for this purpose. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 21873027
TI  - Different patterns of adaptation of the right ventricle to pressure overload: a
      comparison between pulmonary hypertension and pulmonary stenosis.
AB  - BACKGROUND: The study was designed to compare RV morphological and functional
      parameters derived from conventional and myocardial deformation echocardiography
      in two instances of right heart pressure overload: pulmonary arterial
      hypertension (PAH) and pulmonary stenosis (PS). METHODS: Sixty-two individuals
      were included: 22 patients with pulmonary arterial hypertension (PAH), 19
      patients with PS and 21 healthy individuals who served as a control group. All
      patients had clinical evaluation with 6-minute walking test, standard and two
      dimensional strain echocardiography and B-type natriuretic peptide evaluation.
      RESULTS: At similar levels of pressure overload (RV systolic pressure, 88.2 +/-
      31.5 vs 73.4 +/- 34.9 mm Hg; P = NS) the right ventricles of patients with PS
      were less dilated (RV end-diastolic diameter, 31.7 +/- 3.7 vs 43.7 +/- 10.5 mm; P
      < .001) and performed significantly better than those of patients with PAH (RV
      strain, -27.4 +/- 5.8% vs 16.2 +/- 7.9%; RV fractional area change, 51.1 +/- 9.2%
      vs 29.1 +/- 11.3%; P < .001). Although some of the RV functional parameters were
      comparable with those in healthy individuals, strain rate showed lower values,
      suggesting subclinical longitudinal dysfunction in patients with PS. Myocardial
      stress biomarkers were correlated with RV systolic pressure only in patients with
      PAH (r = 0.64, P = .03), not in those with PS (r = 0.22, P = .50). CONCLUSIONS:
      At similar levels of pressure overload, the right ventricle is less dilated and
      performs better in patients with PS compared with those with PAH.

PMID- 21873028
TI  - Abnormalities in cardiac structure and function in adults with sickle cell
      disease are not associated with pulmonary hypertension.
AB  - BACKGROUND: In sickle cell disease (SCD), pulmonary hypertension (assessed by
      tricuspid regurgitant jet [TRJ] velocity >= 2.5 m/sec) is associated with
      increased mortality. The relationships among TRJ velocity and left ventricular
      (LV) and right ventricular (RV) systolic and diastolic function (i.e., relaxation
      and compliance) have not been well characterized in SCD. METHODS: A prospective
      study was conducted in 53 ambulatory adults with SCD (mean age, 34 years; range,
      21-65 years) and 33 African American controls to define the relationship between
      LV and RV function and TRJ velocity using echocardiography. RESULTS: Subjects
      with SCD had larger left and right atrial volumes and increased LV mass compared
      with controls. When patients with SCD were compared with controls, LV and RV
      relaxation (i.e., E') were similar. Among subjects with SCD, pulmonary
      hypertension (TRJ >= 2.5 m/sec) was present in 40%. Higher TRJ velocity was
      correlated with larger left atrial volumes in patients with SCD. Additionally,
      some measures of LV (peak A, lateral and septal annular E/E' ratio) and RV
      (tricuspid valve E/E' ratio) compliance were correlated with TRJ velocity. No
      other measures of LV and RV systolic function or LV diastolic function (i.e.,
      relaxation and compliance) were associated with TRJ velocity. CONCLUSIONS:
      Ambulatory adults with SCD exhibited structural (i.e., LV and RV chamber
      enlargement) and functional (i.e., higher surrogate measures of LV and RV filling
      pressure) abnormalities compared with the control group. In subjects with SCD,
      few abnormalities of LV and RV structure and function were associated with TRJ
      velocity.

PMID- 21873029
TI  - Physiological basis and clinical significance of left ventricular suction studied
      using echo-dynamography.
AB  - BACKGROUND: The existence as well as the exact genesis of left ventricular
      suction during rapid filling phase have been controversial. In the present study,
      we aimed at resolution of this problem using noninvasive and sophisticated
      ultrasonic methods. The clinical meaning was also documented. METHODS: Ten
      healthy male volunteers were examined by 2D echocardiography and echo
      dynamography which enables us to obtain detailed instantaneous data of blood flow
      and wall motion simultaneously from the wide range of the left ventricle. The
      correlation of blood flow and wall motion was also studied. RESULTS: Rapid
      ventricular filling was divided into 2 phases which had different physiology. The
      early half (early rapid filling: ERF) showed the effect which was alike drawing a
      piston. This was proved by the shape of the velocity of inflow and the basal
      muscle contraction which actively assisted extension of the relaxed apical and
      central parts of the left ventricle, giving the negative pressure which causes
      the ventricular suction. The later half (late rapid filling: LRF) showed the
      turning of the fundamental flow and the squeezed basal part just like the
      sphincter in addition to the expansion of the apical and central portions of the
      left ventricle, and all of these cooperatively augmented the suction effect.
      CONCLUSION: Ventricular suction does exist to help ventricular filling.
      Simultaneous appearance of the contraction in the basal part and the relaxation
      or extension in the apical part during the post-ejection transitional period was
      made to occur the suction in the LV. And it can be said that the suction appeared
      in the late stage of systole as the one of the serial systolic phenomena.

PMID- 21873030
TI  - Myoclonic astatic epilepsy: an age-dependent epileptic syndrome with favorable
      seizure outcome but variable cognitive evolution.
AB  - The objective of the study was to explore clinical, electroencephalography (EEG),
      neuropsychological features and prognosis of myoclonic-astatic epilepsy (MAE). Of
      327 children aged between 1 and 9 years with a diagnosis of generalized epilepsy
      followed between 2000 and 2008, 18 (5.5%) had MAE. Male significantly
      predominated (88.9%). Age at onset ranged from 2.3 to 4.9 years (mean 3.6 years).
      Median follow-up period was 6.3 years. In addition to myoclonic-astatic seizures
      patients had myoclonic seizures (66.7%), drop attacks (72.2%), head drops (77.8%)
      absences (88.9%), tonic-clonic generalized seizure (77.8%), tonic seizures
      (38.9%), non-convulsive status epilepticus (16.7%). Seven patients (38.9%) had an
      epileptic encephalopathy. At onset, interictal epileptiform and slow
      abnormalities were recorded, respectively, in 100% and 77.8% of patients. EEG
      abnormalities disappeared in all patients within 4 years since the onset. At long
      term follow-up, two patients developed focal abnormalities typical of rolandic
      epilepsy and two patients photosensitivity. On neuropsychological testing 66.7%
      of patients had a normal IQ (mean 81.2+/-17.0, range 47-105, median 84.5) after a
      mean period of 4.4 years since the last seizure. Sixteen out of 18 patients
      remitted within 3.5 years since the onset and in two patients tonic seizures
      persisted. MAE is generalized childhood epilepsy: although cognitive functions
      might deteriorate, outcome is good regarding seizures.

PMID- 21873031
TI  - Automated quantitative FLAIR analysis in hippocampal sclerosis.
AB  - PURPOSE: To describe and evaluate a novel MRI post-processing technique for
      automated quantitative hippocampal FLAIR analysis in patients with hippocampal
      sclerosis (HS). PATIENTS AND METHODS: Based on a method for FLAIR analysis
      presented by Focke et al. (2009), T1 and coregistered FLAIR scans of individual
      subjects were processed together in SPM5 to conduct both a spatial and an
      intensity normalization of the FLAIR scans. In a further development described
      here, the resulting normalized FLAIR images were thresholded and weighted by a
      probabilistic hippocampal mask to determine the average FLAIR intensities of left
      and right hippocampus. The method was applied to the MRI data of 103 HS patients
      and 131 controls. Using a 95% confidence region calculated from the FLAIR
      intensities of controls as threshold, the performance in discriminating both
      groups was assessed. RESULTS: One hundred of 103 patients and among those all 23
      patients with histologically confirmed HS fell outside the 95% confidence region,
      amounting to 97.1% sensitivity. All but 6 controls (=95.4%) were found within the
      confidence region, corresponding to the expected specificity. The method could
      also distinguish bilateral HS and visualize signal changes after status
      epilepticus. CONCLUSION: Automated FLAIR analysis is a promising tool to quantify
      hippocampal signal alterations, to support the detection of HS, and to monitor
      the temporal evolution of the disease.

PMID- 21873032
TI  - Placebo response trajectories in short-term and long-term antipsychotic trials in
      schizophrenia.
AB  - Increasing rates of placebo response have eroded placebo-control group
      differences in randomized controlled trials, although the reasons for this trend
      remain unclear. Data were extracted from the placebo arms in two identically
      designed 6-week studies and one 52-week study in the ziprasidone clinical trial
      database. The objective of this analysis was to identify distinct patterns of
      placebo response trajectories that could capture individual variability in the
      time course of change during a 1-year trial using growth mixture latent class
      analyses. These long-term placebo response patterns were contrasted with two 6
      week schizophrenia studies. The placebo response trajectory analysis that showed
      58% (Group 4) had gradual improvement in the PANSS negative subscale score
      (p<0.05), fewer dropouts (p<0.05) and improvement in abnormal movements,
      contrasted with 3 other trajectory groups that showed worsening on these
      measures. Almost all subjects (98%) in this symptom improvement group were
      treated with conventional antipsychotics just prior to placebo treatment. In
      contrast, the trajectory analyses showed worsening of symptoms based on PANSS
      total score in the 1-year trial (+15.5, SEM 2.6). Some gradual improvement of
      symptoms (-14.0, SEM 1.6) was also noted in 67% (n=114) of patients in the 6-week
      short term trials. Our findings indicate that substantial heterogeneity in
      placebo response occurs in both short-term and long-term trials. The placebo
      response trajectories appeared to depend on the efficacy measure of symptom
      reduction chosen, prior antipsychotic use profile, and trial durations. Further
      research is warranted to examine the trajectory patterns of placebo responses in
      independent patient populations.

PMID- 21873033
TI  - Class 1 integrons in environmental and clinical isolates of Pseudomonas
      aeruginosa.
AB  - The aims of this study were to ascertain the presence and spread of class 1
      integrons amongst environmental and clinical isolates of Pseudomonas aeruginosa
      and to characterise their variable regions. A total of 76 isolates (56 clinical
      and 20 environmental) were studied. The presence of plasmids was explored, and
      polymerase chain reaction (PCR) was used for integron detection. All amplicons
      were sequenced. PCR detected class 1 integrons in 26 of the 56 clinical isolates;
      environmental isolates were integron-free. No plasmids were found, thus all the
      integrons found are possibly on the chromosome. Most isolates presented one
      amplicon, except PA110514 and PA116136, which showed two PCR products each.
      Variable regions revealed that 18 strains carried only one gene involved in
      aminoglycoside resistance, whereas in 3 strains gene cassettes were not found.
      The most prevalent cassettes amongst isolates were those encoding aminoglycoside
      adenyltransferase B (aadB). Several of the strains had acquired the same or a
      highly similar cassette array as those detected in geographically distant P.
      aeruginosa. This finding suggests that contact with bacterial reservoirs
      contributes to the evolution of this pathogen towards multiresistance. Empty
      structures found may represent a reservoir increasing the capacity to adapt to
      the environment. However, these integrons are not retained when the selective
      pressure disappears. It is hypothesised that integrons containing gene cassettes
      are crucial vehicles for the rapid horizontal transfer of resistance. If this is
      so, reduced use of antibiotics may lead to a significant decrease in the carriage
      of integrons amongst P. aeruginosa strains.

PMID- 21873034
TI  - Epidemiology and molecular characterisation of metallo-beta-lactamase-producing
      Enterobacteriaceae in a university hospital Intensive Care Unit in Greece.
AB  - The molecular epidemiology of VIM-producing Enterobacteriaceae isolated at the
      beginning of an epidemic in the Intensive Care Unit (ICU) of a university
      hospital in Athens, Greece, was studied. All Gram-negative organisms isolated
      from March 2004 to November 2005 positive for metallo-beta-lactamase (MBL)
      production were submitted to polymerase chain reaction (PCR) and sequencing, to
      repetitive sequence-based PCR (Rep-PCR) for molecular typing, and to S1 nuclease
      digestion for plasmid DNA characterisation. Conjugation experiments and
      isoelectric focusing were performed to identify co-existing beta-lactamases.
      Amongst 23 patients, 12 suffered one or more clinical infections. Eighty-two
      isolates representing one isolate per clone, source and ICU patient were studied,
      including Klebsiella pneumoniae (77), Enterobacter cloacae (2), Citrobacter
      freundii (1) and Pseudomonas aeruginosa (2). High clonal diversity was detected
      amongst the K. pneumoniae, with 10 distinct clones identified. Conjugation was
      successful in 54.5% of K. pneumoniae, and five different-sized plasmids were
      detected. All K. pneumoniae and both E. cloacae isolates shared the same bla(VIM
      1)-containing class 1 integron structure also carrying aacA7, dhfrI and aadA1
      gene cassettes. The C. freundii isolate carried a different integron that
      included bla(VIM-1) and aac(6')-IIc. Both P. aeruginosa isolates were positive
      for bla(VIM-2). It was not possible to identify specific clones with the
      potential to cause clinical infections. In conclusion, a multiclonal cluster of
      MBL-producers was responsible for the first cases of colonisation and/or
      infection in the ICU. A single integron structure, common in Greek hospitals,
      efficiently disseminated between clones and species, suggesting that the epidemic
      was mainly the result of successful horizontal transfer of mobile genetic
      material rather than the result of horizontal transfer of one or a few clones.

PMID- 21873036
TI  - Cancer risks in the Druze Isifya Village: Reasons and RF/MW antennas.
AB  - BACKGROUND: The present study was initiated to examine the claims of the
      residents of the Druze Isifya Village in Northern Israel that their high cancer
      rates were associated with the past exposures to radiation from radio and
      cellular transmitters. OBJECTIVE: To investigate the association between past
      exposure to RF/MW transmitters and cancer risks, taking into account familial
      cancer history, occupational exposures and indicators of life-style. METHODS: We
      carried out a population-based case-control study involving 307 residents, of
      whom 47 were diagnosed between 1989 and 2007 with different types of cancer and
      260 controls. Cancer diagnoses were obtained from medical the records. Exposure
      status of individual houses were determined from a map, based on the distances
      between each house and RF/MW antennas, and were calculated using geographic
      information systems (GIS) tools. Data on additional risk factors for cancer, like
      smoking and occupation, were obtained from individual questionnaires. The
      analysis was adjusted for measures of life style and occupational exposure, and
      Binary multiple logistic regressions was used, for all cancer sites and for
      individual cancer types for those cancers with at least 5 documented cases.
      RESULTS: Past occupational exposures to chemicals (e.g., pesticides) and
      electronics, were found to be strongly associated with increased cancer risks
      (all sites: OR=2.79; CI=1.14-6.82; P<0.05), but no discernible trend in overall
      cancer risk was associated with proximity to sources of past RF/MW radiation
      exposure (n=47 OR=1.00; CI=0.99-1.02; P>0.4). Colorectal cancer showed a
      negligible elevated adjusted risk associated with radiation intensity (n=11
      OR=1.03; CI=1.01-1.05; P<0.01). CONCLUSION: There was evidence for an increased
      risk of cancers which were associated with chemicals in manufacturing and
      agriculture and electronics, where there may have been exposures to EMF, but the
      study did not confirm the suspicion of increased cancer risks associated with
      radiation for most cancer types in this village. Misclassification of past
      exposures could explain the negative finding.

PMID- 21873035
TI  - Altered transfer of visual motion information to parietal association cortex in
      untreated first-episode psychosis: implications for pursuit eye tracking.
AB  - Visual motion processing and its use for pursuit eye movement control represent a
      valuable model for studying the use of sensory input for action planning. In
      psychotic disorders, alterations of visual motion perception have been suggested
      to cause pursuit eye tracking deficits. We evaluated this system in functional
      neuroimaging studies of untreated first-episode schizophrenia (N=24), psychotic
      bipolar disorder patients (N=13) and healthy controls (N=20). During a passive
      visual motion processing task, both patient groups showed reduced activation in
      the posterior parietal projection fields of motion-sensitive extrastriate area
      V5, but not in V5 itself. This suggests reduced bottom-up transfer of visual
      motion information from extrastriate cortex to perceptual systems in parietal
      association cortex. During active pursuit, activation was enhanced in anterior
      intraparietal sulcus and insula in both patient groups, and in dorsolateral
      prefrontal cortex and dorsomedial thalamus in schizophrenia patients. This may
      result from increased demands on sensorimotor systems for pursuit control due to
      the limited availability of perceptual motion information about target speed and
      tracking error. Visual motion information transfer deficits to higher-level
      association cortex may contribute to well-established pursuit tracking
      abnormalities, and perhaps to a wider array of alterations in perception and
      action planning in psychotic disorders.

PMID- 21873037
TI  - [Medication errors: analysis of a digoxin overdose case in a neonatology unit].
AB  - Neonatology and pediatrics are units where medication errors occur. Indeed, the
      complexity of nursing care, the lack of information and marketing authorization
      for drugs contribute to the occurrence of often underestimated iatrogenic events.
      Through a case of digoxin overdose in a neonatology unit, each stage of the drug
      circuit was analyzed. From prescription to administration to dispensation, the
      accumulation of individual errors put a newborn in danger. The analysis and
      declaration of such events can improve safety and the quality of patient care.

PMID- 21873038
TI  - [Does the regional health care organization impact the outcome of infants born
      with congenital diaphragmatic hernia?].
AB  - INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a serious pathology that
      requires optimal management in very specialized health centers. French medical
      care organization is regionally based. Hence, evaluating local practices may help
      deliver clear information to parents before delivery. The aim of this study was
      to analyze the neonatal characteristics and the postnatal outcome of infants
      affected with CDH, treated within two different French perinatal health care
      networks. PATIENTS AND METHODS: Retrospective cohort study of infants with CDH,
      cared for in the Lorraine perinatal health care network (Reseau Perinatal Lorrain
      [RPL]) or at Edouard-Herriot Hospital (HEH) in Lyon, between 1997 and 2007.
      RESULTS: One hundred and twenty-seven newborns were included, 44 in the RPL and
      83 in Lyon. Prenatal diagnosis of CDH was similar in RPL and at HEH; 47.7% of
      infants with CDH died in RPL vs 36.1% in HEH (P=0.2). Surgery delayed for more
      than 24h was more frequent in RPL (68.6% vs 31.7%; P<0.001), with a postoperative
      mortality rate of 31.4% vs 15.9%; P=0.08. In RPL, specialized medical follow-up
      was rare (33.3% vs 100%; P<0.001), while psychomotor retardation was more
      frequent (33.3% vs 5.7%; P=0.002). CONCLUSION: This study brings to light the
      diversity of care and outcome for infants affected with CDH in two French
      perinatal health care networks. These results may help improve both centers'
      practices. In Lorraine for instance, the follow-up of these vulnerable children
      can be improved.

PMID- 21873039
TI  - [Congenital human African trypanosomiasis: an observation at the University
      Hospital of Brazzaville (Congo)].

PMID- 21873040
TI  - [Enzyme replacement therapy for lysosomal storage disorders].
AB  - In the last years, much progress has been achieved in the treatment of lysosomal
      storage disorders. Until recently only symptomatic treatment was available for
      the affected patients. Progressively enzyme replacement treatments have been
      developed for several diseases, namely Gaucher disease, Fabry disease,
      mucopolysaccharidoses type I, II and VI and Pompe disease. In this review we will
      summarize the efficacy and safety of these treatments and describe new
      therapeutic trials for other lysosomal storage disorders or perspectives in the
      use of currently available treatments.

PMID- 21873041
TI  - Smoking and asthma: disentangling their mutual influences using a longitudinal
      approach.
AB  - BACKGROUND: The association between smoking and asthma remains unclear and has
      mostly been assessed in cross-sectional studies, with potential selection bias
      ("healthy smoker effect"). AIMS: Using a longitudinal approach, the aims were to
      assess whether 1) childhood asthma modifies smoking initiation, 2) active smoking
      influences asthma incidence in adults and 3) active smoking among subjects with
      asthma influences the persistence of the disease or the 12-year evolution in lung
      function in children and adults. METHODS: Subjects (513 children and 1190 adults)
      were recruited and followed-up for 12 years in the context of the EGEA study
      (Epidemiological study on the Genetics and Environment of Asthma). RESULTS:
      Childhood asthma was not associated with a decreased probability of starting
      active smoking (Hazard Ratio, HR = 0.96; 95% confidence interval (CI): 0.72,
      1.27). Smoking at baseline was associated with a higher risk for asthma incidence
      in adulthood (HR = 1.95, 95% CI: 1.00, 3.77). Among subjects with asthma, smoking
      was unrelated to lung function evolution; however, among children with moderate
      to severe asthma at inclusion, smoking tended to slow down the lung function
      growth (P = 0.04). CONCLUSION: These findings support the hypothesis that
      childhood asthma does not prevent smoking initiation and confirm that active
      smoking has a deleterious role on asthma. Altogether this study emphasizes the
      importance of active smoking as a serious public health problem particularly for
      children and women.

PMID- 21873042
TI  - Impacts of natural weathering on the transformation/neoformation processes in
      landfilled MSWI bottom ash: a geoenvironmental perspective.
AB  - Natural weathering processes are significant mechanisms that noticeably affect
      the fundamental nature of incineration ash residues. To provide a greater
      understanding of these processes, a MSWI (mono)landfill site in the north east of
      the US was selected as the target for systematic investigation of the natural
      weathering of bottom ash residues. Samples of various ages were collected from
      locations A (1 yr), B (10 yrs), C (13-14 yrs) and D (20 yrs) of the landfill in
      2009. We investigated the phase transformation of the collected bottom ash
      particles, neoformation processes as well as the behavior and distribution of
      certain heavy metals (Cu, Pb, Zn, Ni, and Cr) in the neoformed phases using
      optical microscopy, SEM-EDX, and bulk examinations. KEY FINDINGS: at the
      preliminary stage, the waste metallic particles (Al, Fe, and Cu) and unstable
      minerals such as lime, portlandite, ettringite and hydrocalumite convert to oxide
      and hydroxide (hydrate) phases, calcite, alumina gel and gypsum. At the
      intermediate stage, the decomposition of melt products including magnetite
      spinels and metallic inclusions is triggered due to the partial dissolution of
      the melt glass. At the longer time horizon it is possible to track the breakdown
      of the glass phase, the extensive formation of calcite and anhydrite, Al-hydrates
      and more stable Fe-hydrates all through the older ash deposits. Among the
      dominant secondary phases, we propose the following order based on their direct
      metal uptake capacity: Fe-hydrates>Al-hydrates>>calcite. Calcite was found to be
      the least effective phase for the direct sorption of heavy metals. Based on
      overall findings, a model is proposed that demonstrates the general trend of ash
      weathering in the landfill.

PMID- 21873043
TI  - Greatly enhanced detection of a volatile ligand at femtomolar levels using
      bioluminescence resonance energy transfer (BRET).
AB  - Our goal is to develop a general transduction system for G-protein coupled
      receptors (GPCRs). GPCRs are present in most eukaryote cells and transduce
      diverse extracellular signals. GPCRs comprise not only the largest class of
      integral membrane receptors but also the largest class of targets for therapeutic
      drugs. In all cases studied, binding of ligand to a GPCR leads to a sub-nanometer
      intramolecular rearrangement. Here, we report the creation of a novel chimaeric
      BRET-based biosensor by insertion of sequences encoding a bioluminescent donor
      and a fluorescent acceptor protein into the primary sequence of a GPCR. The
      BRET(2)-ODR-10 biosensor was expressed in membranes of Saccharomyces cerevisiae.
      Assays conducted on isolated membranes indicated an EC(50) in the femtomolar
      range for diacetyl. The response was ligand-specific and was abolished by a
      single point mutation in the receptor sequence. Novel BRET-GPCR biosensors of
      this type have potential application in many fields including explosive
      detection, quality control of food and beverage production, clinical diagnosis
      and drug discovery.

PMID- 21873044
TI  - Immobilization of rat brain acetylcholinesterase on ZnS and poly(indole-5
      carboxylic acid) modified Au electrode for detection of organophosphorus
      insecticides.
AB  - A novel, highly sensitive amperometric biosensor for detection of
      organophosphorus (OP) compounds has been constructed, based on rat brain
      acetylcholinesterase (AChE) immobilized onto nanocomposite of ZnS-nanoparticles
      (ZnSNPs) and poly(indole-5-carboxylic acid) electrodeposited on Au electrode. In
      the presence of acetylthiocholine chloride (ATCl) as a substrate, ZnSNPs promoted
      electron transfer reactions at a lower potential and catalyzed electrochemical
      oxidation of enzymatically formed thiocholine, thus increasing detection
      sensitivity. Under optimum conditions (phosphate buffer, pH 7.5 and 30 degrees
      C), the inhibition of AChE by malathion and chlorpyrifos was proportional to
      their concentrations in the range, 0.1-50nM and 1.5-40nM, respectively. The
      biosensor determined malathion and chlorpyrifos in spiked tap water samples with
      a acceptable accuracy (95-100%). The enzyme electrode had long-storage stability
      (50% retention of initial activity within 2 months, when stored at 4 degrees C).

PMID- 21873045
TI  - Scaling of morphogen gradients.
AB  - Individuals of the same or closely related species can vary substantially in
      size. Still, the proportions within and between tissues are precisely kept. This
      adaptation of pattern with size termed scaling, is receiving a growing attention.
      We review experimental evidence for scaling, and describe theoretical models for
      mechanisms that scale morphogen gradients. We particularly note the Expansion
      Repression mechanism, in which a diffusible molecule that positively regulates
      the morphogen gradient width is repressed by morphogen signaling. The Expansion
      Repression circuit provides scaling in a robust manner and is readily implemented
      by a host of molecular mechanisms. We suggest means for identifying such a
      circuit in a system of interest.

PMID- 21873046
TI  - Neural circuit models for computations in early visual cortex.
AB  - Some cortical circuit models study the mechanisms of the transforms from visual
      inputs to neural responses. They model neural properties such as feature tunings,
      pattern sensitivities, and how they depend on intracortical connections and
      contextual inputs. Other cortical circuit models are more concerned with
      computational goals of the transform from visual inputs to neural responses, or
      the roles of the neural responses in the visual behavior. The appropriate
      complexity of a cortical circuit model depends on the question asked. Modeling
      neural circuits of many interacting hypercolumns is a necessary challenge, which
      is providing insights to cortical computations, such as visual saliency
      computation, and linking physiology with global visual cognitive behavior such as
      bottom-up attentional selection.

PMID- 21873047
TI  - Correlation between the release of sugars and uronic acid and free oil recovery
      following enzymatic digestion of oil seed cell walls.
AB  - Aqueous extraction of sunflower seeds and rapeseeds with mixtures of hydrolytic
      enzymes were carried out in 2-L reactor and uronic acid and reducing sugar
      concentrations were measured during digestion. The goal of the study was to
      determine if a correlation between those concentrations and free oil exists that
      would allow predicting free oil release from aqueous solution measurements.
      Similar concentrations of 4.5 and 4.7 g/L of reducing sugars and 43 and 55 g/L of
      uronic acid were found for sunflower and rapeseeds, respectively. The
      corresponding yields of free oil from the two seeds were 83% and 16% of total
      oil, and this difference was due to the formation of an emulsion in the rapeseed
      dispersion. Therefore, measurement of reducing sugars or uronic acid
      concentrations are not sufficient to predict a release of free oil from all oil
      seeds.

PMID- 21873048
TI  - Isolation and analysis of wax esters from activated sludge.
AB  - Neutral lipid from activated sludge (AS) as a potential source for biodiesel
      production has recently received considerable attentions. The utilization of
      useful compounds in AS may help reducing the cost of biodiesel production from
      AS. One of these compounds is the valuable wax esters (WEs) found in AS from a
      food processing company in Taiwan. About 4.13% (based on dry sludge weight)
      bleached wax was obtained after pretreatment and bleaching of crude sludge wax
      obtained from the dewaxing of crude sludge oil. The major WEs detected in the
      bleached wax were C46-C60 with small amounts of C37-C43 and C62 WEs. The fatty
      acids (FAs) and fatty alcohols (FALs) profiles of WEs were also investigated.
      Activated sludge WEs are mainly mixture of C14-C28 FAs and C24-C37 FALs, in which
      the predominant FAs are C16 and C18 while the predominant FALs are C32 and C34.

PMID- 21873049
TI  - Synthesis and in-vitro anticancer activity of 3,5-bis(indolyl)-1,2,4
      thiadiazoles.
AB  - A series of 3,5-bis(indolyl)-1,2,4-thiadiazoles were synthesized and evaluated
      for their cytotoxicity against selected human cancer cell lines. The reaction of
      indole-3-thiocarboxamide 3 with iodobenzene diacetate underwent oxidative
      dimerization to give 3,5-bis(indolyl)-1,2,4-thiadiazoles 4a-n. Among the
      synthesized bis(indoly)-1,2,4-thiadiazoles, the compound 4h with 4-chlorobenzyl
      and methoxy substituents showed the most potent activity.

PMID- 21873050
TI  - Identification of novel BRAF kinase inhibitors with structure-based virtual
      screening.
AB  - VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has proved to be a
      promising target for the development of therapeutics for the treatment of a
      variety of human cancers. Here, we report the first example of a successful
      application of the structure-based virtual screening to identify novel BRAF
      inhibitors. These inhibitors have desirable physicochemical properties as a drug
      candidate, and compound 1 revealed a submicromolar binding affinity (0.7 MUM).
      Therefore, they may serve as promising lead compounds for further development by
      structure-activity relationship (SAR) studies to optimize the inhibitory
      activities. Structural features relevant to the stabilization of the newly
      identified inhibitors in the ATP-binding site of BRAF are discussed in detail.

PMID- 21873051
TI  - Discovery of BI 99179, a potent and selective inhibitor of type I fatty acid
      synthase with central exposure.
AB  - Based on a high-throughput screen, cyclopentanecarboxanilides were identified as
      a new chemotype of non-covalent inhibitors of type I fatty acid synthase (FAS).
      Starting from initial hits we aimed at generating a tool compound suitable for
      the in vivo validation of FAS as a therapeutic target. Optimisation yielded BI
      99179 which is characterised by high potency, remarkably high selectivity and
      significant exposure (both peripheral and central) upon oral administration in
      rats.

PMID- 21873052
TI  - Synthesis and evaluation of compounds that induce readthrough of premature
      termination codons.
AB  - A structure-activity relationship (SAR) study was carried out to identify novel,
      small molecular weight compounds which induce readthrough of premature
      termination codons. In particular, analogs of RTC13, 1, were evaluated. In
      addition, hypothesizing that these compounds exhibit their activity by binding to
      the ribosome, we prepared the hybrid analogs 13 containing pyrimidine bases and
      these also showed good readthrough activity.

PMID- 21873053
TI  - Improved synthesis and biological evaluation of chelator-modified alpha-MSH
      analogs prepared by copper-free click chemistry.
AB  - Radionuclide chelators (DOTA, NOTA) functionalized with a monofluorocyclooctyne
      group were prepared. These materials reacted rapidly and in high yield with a
      fully deprotected azide-modified peptide via Cu-free click chemistry under mild
      reaction conditions (aqueous solution, room temperature). The resulting
      bioconjugates bind with high affinity and specificity to their cell-surface
      receptor targets in vitro and appear stable to degradation in mouse serum over 3h
      of incubation at 37 degrees C.

PMID- 21873054
TI  - Synthesis and biological evaluation of alpha,beta-unsaturated lactones as potent
      immunosuppressive agents.
AB  - Compounds having alpha,beta-unsaturated lactones display a variety of biological
      activities. Many research groups have tested both natural and unnatural
      alpha,beta-unsaturated lactones for as-yet undiscovered biological properties. We
      synthesized alpha,beta-unsaturated lactones with various substituents at the
      delta-position and studied their immunosuppressive effects, that is, the
      inhibition of Interleukin-2 (IL-2) production. Among the compounds synthesized,
      the benzofuran-substituted alpha,beta-unsaturated lactone 4h showed the best
      inhibitory activity toward IL-2 production in Jurkat e6-1 T lymphocytes
      (IC(50)=66.9 nM) without cytotoxicity at 10 MUM. The results indicated that 4h
      may be useful as a potent immunosuppressive agent, as well as in IL-2-related
      studies.

PMID- 21873055
TI  - Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3
      gene.
AB  - G-Quadruplexes have been proved to exist in 5'-untranslated region (5'-UTR),
      promoter, intron and exon regions of many human genes. Here we report an
      intramolecular G-quadruplex formed by a G-rich sequence in the 3'-flanking region
      of signal transducers and activators of transcription 3 (STAT3) gene. The results
      showed that this G-rich sequence could affect the expression of STAT3. When the
      STAT3 G-quadruplex was stabilized by a novel non-planar ligand Cepharanthine
      (CEP), the decreased expression of STAT3 was observed in primary cultured
      cardiomyocytes. We also demonstrated that the down-regulation of STAT3 was most
      likely occurred at the transcriptional level. Our results provide a new clue for
      studying the G-quadruplex formation, recognition and function in the 3'-flanking
      region of gene.

PMID- 21873056
TI  - Development of 2-substituted-N-(naphth-1-ylmethyl) and N-benzhydrylpyrimidin-4
      amines as dual cholinesterase and Abeta-aggregation inhibitors: Synthesis and
      biological evaluation.
AB  - A group of 2-substituted N-(naphth-1-ylmethyl)pyrimidin-4-amines (6a-k) and N
      benzhydrylpyrimidin-4-amines (7a-k) in conjunction with varying steric and
      electronic properties at the C-2 position were designed, synthesized and
      evaluated as dual cholinesterase and amyloid-beta (Abeta)-aggregation inhibitors.
      The naphth-1-ylmethyl compound 6f (2-(4-cyclohexylpiperazin-1-yl)-N-(naphth-1
      ylmethyl)pyrimidin-4-amine) exhibited optimum dual ChE (AChE IC(50)=8.0 MUM,
      BuChE IC(50)=3.9 MUM) and hAChE-promoted Abeta-aggregation inhibition (30.8% at
      100 MUM), whereas in the N-benzhydryl series, compound 7f (N-benzhydryl-2-(4
      cyclohexylpiperazin-1-yl)pyrimidin-4-amine) exhibited optimum combination of dual
      ChE (AChE IC(50)=10.0 MUM, BuChE IC(50)=7.6MUM) and hAChE-promoted Abeta
      aggregation inhibition (32% at 100 MUM). These results demonstrate that a 2,4
      disubstituted pyrimidine ring serves as a suitable template to target multiple
      pathological routes in AD, with a C-2 cyclohexylpiperazine substituent providing
      dual ChE inhibition and potency whereas a C-4 diphenylmethane substituent
      provides Abeta-aggregation inhibition.

PMID- 21873057
TI  - Potent and novel 11beta-HSD1 inhibitors identified from shape and docking based
      virtual screening.
AB  - Several potent and novel 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1)
      inhibitors were discovered from in silico screening the commercially available
      Maybridge database. Among them, seven hit compounds showed good affinity, with
      IC(50) values lower than 100 nM and the best one 3.7 nM. To select the lead for
      further optimization, computational ADME/T prediction, the CYP3A4 inhibition and
      11beta-HSD1 over 11beta-HSD2 selectivity test were also performed. Taking all of
      the above factors into consideration, two promising compounds were selected as
      lead structures for further development. The employed hierarchical virtual
      screening protocol not only demonstrates its efficiency, but also provides novel
      and selective compounds for developing 11beta-HSD1 inhibitors to protect against
      metabolic syndrome.

PMID- 21873058
TI  - Microbial metabolism. Part 13. Metabolites of hesperetin.
AB  - The fungal culture, Mucor ramannianus (ATCC 2628) transformed hesperitin (1) to
      four metabolites: 4'-methoxy-5,7,8,3'-tetrahydroxyflavanone (8-hydroxyhesperetin)
      (2), 5,7,3',4'-tetrahydroxyflavanone (eriodictyol) (3), 4'-methoxy-5,3'
      dihydroxyflavanone 7-sulfate (hesperetin 7-sulfate) (4) and 5,7,3'
      trihydroxyflavanone 4'-O-alpha-quinovopyranoside (eriodictyol 4'-O-alpha
      quinovopyranoside) (5). The structures were established by spectroscopic methods.

PMID- 21873059
TI  - Coprismycins A and B, neuroprotective phenylpyridines from the dung beetle
      associated bacterium, Streptomyces sp.
AB  - Two new phenylpyridines, named coprismycins A and B (1 and 2), and previously
      reported dipyridines (3-6) were isolated from a culture of Streptomyces sp.
      associated with the dung beetle, Copris tripartitus. The structures of the
      coprismycins (1 and 2) were elucidated by the analysis of 1D and 2D NMR spectra
      and mass, UV, and IR spectra. Coprismycins A-B (1 and 2) and dipyridines (5 and
      6) displayed comparable neuroprotective effects against MPP(+) (1-methyl-4
      phenylpyrimidium)-induced neurotoxicity in neuroblastoma SH-SY5Y cells.

PMID- 21873060
TI  - d(TGGGAG) with 5'-nucleobase-attached large hydrophobic groups as potent
      inhibitors for HIV-1 envelop proteins mediated cell-cell fusion.
AB  - The Hotoda's sequence substituted with TBDPS via 5'-end nucleobase existed as
      parallel quadruplex structure and exhibited inhibitory activities in an HIV-1
      envelop proteins mediated cell-cell fusion assay. This result demonstrated that
      the 5'-aromatic groups of the Hotoda's sequence are allowed to have a large
      spatial freedom and remain to be optimized for its role in the binding to HIV-1
      envelop proteins.

PMID- 21873061
TI  - Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid
      based inhibitors of glycogen synthase kinase-3beta.
AB  - The synthesis, GSK-3beta inhibitory activity, and anti-microbial activity of
      bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3
      carboxylic acid scaffold were studied. Kinase selectivity profiling indicated
      that members of this class were potent and highly selective GSK-3 inhibitors.

PMID- 21873062
TI  - Biochemical characterization of the M712T-mutation of the UDP-N-acetylglucosamine
      2-epimerase/N-acetyl-mannosaminekinase in hereditary inclusion body myopathy.
AB  - Hereditary inclusion body myopathy is a neuromuscular disorder characterized by
      muscle weakness with a late onset and slow progression. It is caused by mutations
      of the gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine
      kinase (GNE). One of the most frequent mutations is an exchange of methionine to
      threonine at position 712 (M712T). Here we analyzed wildtype (wt) and M712T
      mutated (M712T) GNE. We identified threonine 712 as an additional possible
      phosphorylation site and found by two-dimensional gel-electrophoresis a lower
      isoelectric point compared to wt-GNE. This lower isoelectric point could be
      partially reversed back to the wildtype isoelectric point after treatment with
      protein phosphatase. Furthermore, in contrast to wt-GNE, a significant fraction
      of M712T-GNE was in the insoluble fraction. Finally, by using bimolecular
      fluorescence complementation we demonstrate that the M712T mutation does not
      disrupt the formation of GNE-oligomers.

PMID- 21873063
TI  - A pilot study to examine the experiences and attitudes of women with breast
      cancer towards one versus two-step axillary surgery.
AB  - PURPOSE: To elicit the views, experiences and preferences of women with
      clinically node negative breast cancer towards intra-operative sentinel lymph
      node biopsy (SLNB) analysis. METHODS: Focus groups with 14 women with breast
      cancer from two UK centres; one group had undergone the standard practice of
      waiting two weeks for results of their axillary surgery, the other had
      experienced the intra-operative SLNB analysis. RESULTS: Women generally were
      unaware about their lymph nodes, what their function is and how they are removed.
      Preference was indicated for intra-operative sentinel lymph node biopsy (SLNB)
      analysis provided clear descriptions were given about the risk of experiencing
      false negative and false positive results. DISCUSSION: Adopting an intra
      operative analysis technique of axillary nodes was viewed as an excellent option
      by women from both centres. The immediacy of knowing the results was seen as a
      great advantage for their physical and psychological well being and more cost
      effective.

PMID- 21873064
TI  - Gait pattern alterations in older adults associated with type 2 diabetes in the
      absence of peripheral neuropathy--results from the Baltimore Longitudinal Study
      of Aging.
AB  - Diabetes may impact gait mechanics before onset of frank neuropathies and other
      associated threats to mobility. This study aims to characterize gait pattern
      alterations of type 2 diabetic adults without peripheral neuropathy during
      walking at maximum speed (fast-walking) as well as at self-selected speed (usual
      walking). One-hundred and eighty-six participants aged 60-87 from the Baltimore
      Longitudinal Study of Aging (BLSA) able to walk unassisted and without peripheral
      neuropathy were classified as non-diabetic (N=160) or having type 2 diabetes
      (N=26). Gait parameters from the fast-walking and usual-walking tests were
      compared between participants with and without type 2 diabetes. Participants with
      diabetes had a shorter stride length for fast-walking (p=0.033) and a longer
      percentage of the gait cycle with the knee in 1st flexion for both fast- and
      usual-walking (p=0.033, and 0.040, respectively) than non-diabetic participants.
      Participants with diabetes exhibited a smaller hip range of motion in the
      sagittal plane during usual-walking compared to non-diabetics (p=0.049). During
      fast-walking, participants with diabetes used lower ankle generative mechanical
      work expenditure (MWE) and higher knee absorptive MWE compared to non-diabetic
      persons (p=0.021, and 0.018, respectively). These findings suggest that
      individuals with type 2 diabetes without overt peripheral neuropathy exhibit
      altered and less efficient gait patterns than non-diabetic persons. These
      alterations are more apparent during walking at a maximum speed indicating that
      maximum gait testing may be useful for identifying early threats to mobility
      limitations in older adults with type 2 diabetes.

PMID- 21873065
TI  - Rectus femoris transfer and musculo-skeletal modeling: effect of surgical
      treatment on gait and on rectus femoris kinematics.
AB  - Spasticity of the rectus femoris (RF) is one of the possible causes of stiff knee
      gait (SKG) in cerebral palsy. Musculoskeletal studies have shown that in SKG,
      length and speed of the RF are affected. No evaluation had been made to quantify
      the modifications of those parameters after surgery. The effect of this operation
      on gait quality and on RF kinematics was assessed in this study in order to
      identify kinematic patterns that may aid its diagnosis. For 26 transfers,
      clinical gait analysis pre- and post-surgery was used to compute the Gait
      Deviation Index (GDI) and Goldberg's index. The kinematics of the Original RF
      path (ORFp) was studied before and after surgery. The expression ORFp was chosen
      to avoid any confusion between this modeling parameter, whose computation was
      unchanged, and the actual anatomical path that was modified by surgery. The gait
      quality was improved (+18+/-12GDI) and there was an inverse relation between the
      pre-operative GDI and its improvement. The Golberg's index was improved (88% of
      the cases). The operation had a significant effect on the normalization of the
      timings of maximum length and speed of the ORFp. The improvement of SKG was
      correlated with the normalization of the timing of the ORFp's maximum length. The
      global improvement of the gait quality and of the SKG was demonstrated. Some
      parameters of muscular kinematics (RF length and velocity) have been
      standardized, showing an effect of the transfer not only during the swing, but
      also during stance. The premature timing of the ORFp peak length has been
      identified as a prognostic factor of a successful surgical outcome.

PMID- 21873066
TI  - Suprasellar meningioma presenting with an altitudinal field defect.
AB  - We report a female patient with an unusual suprasellar meningioma presenting with
      a right-sided inferior altitudinal visual field defect. Two causative factors
      were identified at surgery: an aberrant ophthalmic artery found lying on the
      superior aspect of the optic nerve, and marked compression of the nerve
      superiorly against the falciform ligament.

PMID- 21873067
TI  - Synthesis of pheophorbide-a conjugates with anticancer drugs as potential cancer
      diagnostic and therapeutic agents.
AB  - Pheophorbide-a, a chlorine based photosensitizer known to be selectively
      accumulated in cancer cells, was conjugated with anticancer drugs, doxorubicin
      and paclitaxel in the purpose of selective cancer diagnosis and therapy.
      Pheophorbide-a was conjugated with anticancer drugs via directly and by the use
      of selective cleavage linkers in cancer cell. The fluorescence of pheophorbide-a
      and doxorubicin conjugate by excitation at 420 or 440 nm was greatly diminished
      possibly by the energy transfer mechanism between two fluorescent groups.
      However, upon treatment in cancer cells, the conjugate showed to be cleaved to
      restore each fluorescence of pheophorbide-a and doxorubicin after 48 h of
      incubation. Also, pheophorbide-a conjugates either with doxorubicin and
      paclitaxel inhibited the growth of various cancer cells more potently than
      pheophorbide-a, which displayed very weak inhibitory activity. The results
      indicated that the pheophorbide-a conjugates with anticancer drugs could be
      utilized for selective cancer therapy as well as for the fluorescence detection
      of cancer.

PMID- 21873068
TI  - Synthesis and SAR requirements of adamantane-colchicine conjugates with both
      microtubule depolymerizing and tubulin clustering activities.
AB  - A series of analogues of conjugate 1, combining an adamantane-based paclitaxel
      (taxol) mimetic with colchicine was synthesized and tested for cytotoxicity in a
      cell-based assay with the human lung carcinoma cell line A549. The most active
      compounds (10 EC(50) 2 +/- 1.0 nM, 23 EC(50) 6 +/- 1.4 nM, 26 EC(50) 5 +/- 1.8
      nM, 28 EC(50) 11 +/- 1.7 nM, 30 EC(50) 4.8 +/- 0.5 nM) were found to interfere
      with the microtubule dynamics in an interesting manner. Treatment of the cells
      with these compounds promoted disassembly of microtubules followed by the
      formation of stable tubulin clusters. Structure-activity relationships for the
      analogues of 23 revealed the sensitivity of both cytotoxicity and tubulin
      clustering ability to the linker length. The presence of adamantane (or another
      bulky hydrophobic and non-aromatic moiety) in 23 was found to play an important
      role in the formation of tubulin clusters. Structural requirements for optimal
      activity have been partially explained by molecular modeling.

PMID- 21873069
TI  - Synthesis of benzo[3,4]azepino[1,2-b]isoquinolin-9-ones from 3-arylisoquinolines
      via ring closing metathesis and evaluation of topoisomerase I inhibitory
      activity, cytotoxicity and docking study.
AB  - Benzo[3,4]azepino[1,2-b]isoquinolinones were designed and developed as constraint
      forms of 3-arylisquinolines with an aim to inhibit topoisomerase I (topo I). Ring
      closing metathesis (RCM) of 3-arylisoquinolines with suitable diene moiety
      provided seven membered azepine rings of benzoazepinoisoquinolinones. Spectral
      analyses of these heterocyclic compounds demonstrated that the methylene protons
      of the azepine rings are nonequivalent. The shielding environment experienced by
      these geminal hydrogens differs unusually by 2.21ppm. As expected,
      benzoazepinoisoquinolinones displayed potent cytotoxicity. However, cytotoxic
      effects of the compounds were not related to topo I inhibition which is explained
      by non-planar conformation of the rigid compounds incapable of intercalating
      between DNA base pairs. In contrast, flexible 3-arylisoquinoline 8d attains
      active conformation at drug target site to exhibit topo I inhibition identical to
      cytotoxic alkaloid, camptothecin (CPT).

PMID- 21873070
TI  - SAR studies of acidic dual gamma-secretase/PPARgamma modulators.
AB  - A novel set of dual gamma-secretase/PPARgamma modulators characterized by a 2
      benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the
      variation of the substitution pattern of the central benzene. Finally, we
      obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid
      derivatives, which act as dual gamma-secretase/PPARgamma modulators in the low
      micromolar range. We have explored broad SAR and successfully improved the dual
      pharmacological activity and the selectivity profile against potential off
      targets such as NOTCH and COX. Compound 17 showed an IC(50) Abeta42=2.4 MUM and
      an EC(50) PPARgamma=7.2 MUM and could be a valuable tool to further evaluate the
      concept of dual gamma-secretase/PPARgamma modulators in animal models of
      Alzheimer's disease.

PMID- 21873071
TI  - 5a-Carba-beta-D-glucopyranose derivatives as novel sodium-dependent glucose
      cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes.
AB  - 5a-Carba-beta-D-glucopyranose derivatives were synthesized and identified as
      novel SGLT2-selective inhibitors. These inhibitors exhibited potent SGLT2
      inhibition with high selectivity over SGLT1. Among the tested compounds, 6f
      indicated the most potent hSGLT2 inhibition and the highest selectivity over
      hSGLT1. Moreover, the pharmacokinetics data also showed that 6h, which had the
      same aglycon structure as sergliflozin-active (3-active), had a threefold longer
      half-life time (T(1/2)) than sergliflozin (3) with a high distribution volume in
      db/db mice. Subsequently, 6h lowered blood glucose levels as much as 3 and showed
      longer hypoglycemic action than 3 in db/db mice.

PMID- 21873072
TI  - Protein enrichment by capture-release based on strain-promoted cycloaddition of
      azide with bicyclononyne (BCN).
AB  - An enrichment strategy was devised for azide derivatized macromolecules, based on
      strain-promoted alkyne-azide cycloaddition (SPAAC) and a cleavable linker. A ring
      strained alkyne, bicyclo[6.1.0]non-4-yne (BCN), was covalently attached to
      agarose beads via a hydrazine-sensitive linker. Benchmark studies of the
      resulting 'azido-trap' beads were performed with a fluorogenic coumarin
      derivative, leading to efficient capture of the azidocoumarin with concomitant
      fluorescence staining of the beads via SPAAC. The versatility of the beads for
      specific protein enrichment was shown by an effective and highly specific capture
      release strategy for enrichment of azido-containing Candida antarctica lipase B
      (CalB) from a mixture of proteins. This approach is suited for selective
      enrichment of (glyco)proteins after metabolic incorporation of azides for
      subsequent (glyco)proteomics studies.

PMID- 21873073
TI  - Isolation and structural identification of a direct-acting mutagen derived from N
      nitroso-N-methylpentylamine and Fenton's reagent with copper ion.
AB  - N-Nitrosodialkylamines show their mutagenicity by forming alpha
      hydroxynitrosamines in the presence of rat S9 mix in the Ames assay. The hydroxyl
      radical derived from Fe(2+)-H(2)O(2) (Fenton's reagent) with Cu(2+) activates N
      nitrosamines, with an alkyl chain longer than a propyl constituent, to a direct
      acting mutagen. The reactivity of Fe(2+)-Cu(2+)-H(2)O(2) on nitrosamines in
      relation to their metabolic activation is not fully characterized. Here, we
      report the identification of the direct-acting mutagen derived from N-nitroso-N
      methylpentylamine (NMPe) in the presence of Fe(2+), Cu(2+), H(2)O(2) and nitric
      oxide (NO), which is a product of nitrosamine metabolism. A dichloromethane
      extract of the NMPe reaction mixtures was fractionated by silica gel column
      chromatography several times and by a preparative high performance liquid
      chromatography (HPLC); we obtained white crystals as a product. The direct-acting
      mutagen that was isolated was provisionally identified as 5-ethyl-5-nitro-1
      pyrazoline 1-oxide by (1)H and (13)C nuclear magnetic resonance (NMR)
      spectroscopy, infrared (IR) spectroscopy and X-ray crystallography. To confirm
      the structure of the mutagen, the authentic compound was synthesized from 2
      nitrobutene and diazomethane, followed by N-oxidation with m-chloroperoxybenzoic
      acid. The (1)H NMR spectral data from the direct-acting mutagen that was
      synthesized was identical to the data from the isolated mutagen. Furthermore, the
      authentic 5-ethyl-5-nitro-1-pyrazoline 1-oxide was mutagenic in Salmonella
      typhimurium TA1535. The results showed that 5-ethyl-5-nitro-1-pyrazoline 1-oxide
      was a direct-acting mutagen derived from the reaction of NMPe and Fe(2+)-Cu(2+)
      H(2)O(2)-NO.

PMID- 21873074
TI  - Cloning, purification and characterization of a 90kDa heat shock protein from
      Citrus sinensis (sweet orange).
AB  - Protein misfolding is stimulated by stress, such as heat, and heat shock proteins
      (Hsps) are the first line of defense against these undesirable situations.
      Plants, which are naturally sessile, are perhaps more exposed to stress factors
      than some other organisms, and consequently, the role of Hsps is crucial to
      maintain homeostasis. Hsp90, because of its key role in infection and other
      stresses, is targeted in therapies that improve plant production by increasing
      resistance to both biotic and abiotic stress. In addition, Hsp90 is a primary
      factor in the maintenance of homeostasis in plants. Therefore, we cloned and
      purified Hsp90 from Citrus sinensis (sweet orange). Recombinant C. sinensis Hsp90
      (rCsHsp90) was produced and measured by circular dichroism (CD), intrinsic
      fluorescence spectroscopy and dynamic light scattering. rCsHsp90 formed a dimer
      in solution with a Stokes radius of approximately 62A. In addition, it was
      resistant to thermal unfolding, was able to protect citrate synthase from
      aggregation, and Western blot analysis demonstrated that CsHsp90 was
      constitutively expressed in C. sinensis cells. Our analysis indicated that
      CsHsp90 is conformationally similar to that of yeast Hsp90, for which structural
      information is available. Therefore, we showed that C. sinensis expresses an
      Hsp90 chaperone that has a conformation and function similar to other Hsp90s.

PMID- 21873075
TI  - Risk factors for surgical site infection in cervico-facial oncological surgery.
AB  - INTRODUCTION: Infection after head and neck oncological surgery is relatively
      frequent, and is associated with significant morbidity and mortality. AIM: The
      primary objective of this prospective study was to determine risk factors for
      Surgical Site Infection (SSI) in major head and neck cancer surgery. PATIENTS AND
      METHODS: A population of 137 head and neck cancer patients, of the Portuguese
      Institute of Oncology Francisco Gentil (Lisbon, Portugal), was prospectively
      studied in order to ascertain the correlation between 31 known risk factors and
      the presence of SSI. RESULTS: The rate of SSI was 10.9%, with all of the
      infections being of the deep incisional type. A discriminant analysis and
      multiple logistic regression methods identified pre-surgical tracheostomy (p <
      0.001), previous surgery (p = 0.001) and length of pre-operative hospital stay (p
      < 0.001) as the most significant risk factors for surgical site infections.
      CONCLUSION: In order to minimize the risk of post-operative SSI in the context of
      head and neck cancer patients, particular attention should be paid to patients
      submitted to tracheostomy before surgery, to those submitted to previous
      oncological surgery, and to patients who are forced to remain in the hospital for
      prolonged periods of time before surgery.

PMID- 21873076
TI  - GM-CSF and TNFalpha modulate protein expression of human neutrophils visualized
      by fluorescence two-dimensional difference gel electrophoresis.
AB  - Increased serum levels of TNFalpha and GM-CSF are found in various chronic
      inflammatory diseases and these cytokines affect the function of circulating and
      tissue neutrophils. TNFalpha- and GM-CSF-induced protein expression profiles
      could, therefore, serve as biomarker for the action of these cytokines in vivo.
      We stimulated human peripheral neutrophils with TNFalpha and GM-CSF in vitro and
      analyzed changes in their proteome by fluorescence two-dimensional difference gel
      electrophoresis (2D-DIGE). We report the differential expression of 3 and 18
      protein spots following TNFalpha and GM-CSF stimulation, respectively.
      Differences in protein expression induced by TNFalpha were limited and did not
      show discriminatory power in a principal component analysis, whereas the profile
      induced by GM-CSF did. TNFalpha- and GM-CSF-induced both de novo IL-1beta and sIL
      1Ra protein expression as detected by Western blot analysis, which confirmed
      proper neutrophil activation by these cytokines in vitro. Mass spectrometry
      analysis of cytokine-regulated protein spots resulted in the identification of 8
      proteins. Among the identified proteins, enolase 1 and annexin A1 might function
      as markers for peripheral neutrophil activation. In conclusion, a proteomic
      analysis of neutrophils by 2D-DIGE provides proof-of-principle that cytokine
      induced protein profiles can serve as biomarkers for the action of individual
      cytokines in vivo.

PMID- 21873077
TI  - Current regulatory and scientific considerations for approving biosimilars in
      Iran.
AB  - With the expiration of patents on the first generation of rDNA
      biopharmaceuticals, competitors began to introduce biosimilar products. The
      concept of generics as applied to classical chemical drugs cannot be used for
      biotechnology products. Physicochemical characterization, bioassays and animal
      studies do not have the ability to predict reliably the safety and efficacy of
      biotherapeutics. Clinical studies are always necessary. While regulators all over
      the world were really in need of a comprehensive guideline in this area, WHO
      introduced a guideline which is principally a basis for regulating biosimilars
      and is applicable in Iran, as well as many other countries.

PMID- 21873078
TI  - Biotechnological products in Pan American Health Organization (PAHO): regional
      efforts towards harmonization of regulation.

PMID- 21873079
TI  - Concept of biosimilar products in Jordan.
AB  - After the expiration of patents on originator biological products, Jordanian
      local manufacturers and the agents of international pharmaceutical companies in
      Jordan started to submit registration dossiers for biosimilar products. The
      Jordan Food and Drug Administration (JFDA) is the national regulatory authority
      responsible for the registration of biosimilar products. Biosimilars are
      registered under the same regulations used for drugs until specific guidelines
      for registration of biological and biosimilar products are released. Those
      regulations are called Criteria of Registration of Drugs, Vaccines, Sera and
      Biological Products, the Renewal of its Registration and the Cancellation of Any
      of them which was published in the official gazette in 2004 under the Provisional
      Law Number 80 of the year 2001, Drug and Pharmacy Law and its amendments of the
      year 2003. Also, the JFDA follows the EMA guidelines on similar biological
      medicinal products for specific active biological substances for non-clinical and
      clinical studies requirements and the EMA guideline on similar biological
      medicinal products containing biotechnology-derived proteins as active substance:
      quality issues. A post marketing surveillance study is requested after a
      biosimilar product is authorized. The JFDA keeps pace with all advances in the
      regulatory issues related to biosimilars in order to be capable of authorizing
      biosimilar products with a safe, effective and good quality profile.

PMID- 21873080
TI  - Percutaneous balloon occlusion of a left ventricular assist device outflow
      cannula to facilitate evaluation of myocardial recovery.

PMID- 21873081
TI  - Word associations contribute to machine learning in automatic scoring of degree
      of emotional tones in dream reports.
AB  - Scientific study of dreams requires the most objective methods to reliably
      analyze dream content. In this context, artificial intelligence should prove
      useful for an automatic and non subjective scoring technique. Past research has
      utilized word search and emotional affiliation methods, to model and
      automatically match human judges' scoring of dream report's negative emotional
      tone. The current study added word associations to improve the model's accuracy.
      Word associations were established using words' frequency of co-occurrence with
      their defining words as found in a dictionary and an encyclopedia. It was
      hypothesized that this addition would facilitate the machine learning model and
      improve its predictability beyond those of previous models. With a sample of 458
      dreams, this model demonstrated an improvement in accuracy from 59% to 63%
      (kappa=.485) on the negative emotional tone scale, and for the first time reached
      an accuracy of 77% (kappa=.520) on the positive scale.

PMID- 21873082
TI  - Is the h-index predictive of greater NIH funding success among academic
      radiologists?
AB  - RATIONALE AND OBJECTIVES: Despite rapid adoption of the Hirsch index (h-index) as
      a measure of academic success, the correlations between the h-index and other
      metrics of productivity remain poorly understood. The aims of this study were to
      determine whether h-indices were associated with greater National Institutes of
      Health (NIH) funding success among academic radiologists. MATERIALS AND METHODS:
      Using the Scopus database, h-indices were calculated for a random sample of
      academic radiologists with the rank of professor. Using the NIH tool Research
      Portfolio Online Reporting Tools Expenditures and Reports, we determined the
      number, classification, and total years of NIH grant funding as principal
      investigator for each radiologist. Differences in h-index, sorted by funding
      status, were determined using Wilcoxon's tests. Associations between h-index and
      funding status were determined using logistic regression. Significant
      correlations between h-index and grant metrics were determined using Spearman's
      rho. RESULTS: Among 210 professors of radiology, 48 (23%) secured at least one
      NIH grant. The mean h-index was significantly higher among individuals who
      secured at least one NIH grant (19.1) compared to those who did not (10.4) (P <
      .0001). Professors with h-indices < 10 compared to those with h-indices > 10 were
      significantly less likely to receive NIH funding (odds ratio, 0.07; P = .0321).
      However, h-indices > 10 were not significantly predictive of greater funding. No
      significant relationships were observed between h-index and the number of grant
      awards, years of prior funding, the amounts of grant awards, or grant
      classification. CONCLUSION: Having obtained at least one NIH grant was associated
      with a higher h-index, yet multiple or large grants, such as those for program
      projects, were not predictive of higher h-indices.

PMID- 21873085
TI  - A clinical predicament--diagnosis and differential diagnosis of cutaneous facial
      sinus tracts of dental origin: a series of case reports.
AB  - A cutaneous draining sinus tract of dental origin is often a diagnostic
      challenge, because of its uncommon occurrence and absence of dental symptoms.
      Proper diagnosis, treatment, and the elimination of the source of infection are a
      must; otherwise, it can result in ineffective and inappropriate outcome of
      treatment. This article presents 4 cases of facial lesions misdiagnosed as being
      of nonodontogenic origin. The correct diagnosis in each case was cutaneous sinus
      tract secondary to pulpal necrosis, suppurative apical periodontitis, and
      osteomyelitis. In all cases, facial sinus tracts of dental origin were excised
      and the source of infection eliminated. The purpose of this paper is to provide
      diagnostic guidelines and examination protocols for differential diagnosis of
      cutaneous facial sinus tracts of dental origin.

PMID- 21873086
TI  - Effectiveness of ethylenediaminetetraacetic acid (EDTA) and MTAD on debris and
      smear layer removal using a self-adjusting file.
AB  - OBJECTIVE: The aim of this study was to investigate the cleaning ability of a
      self-adjusting file (SAF) system regarding debris and smear layer removal using
      ethylenediaminetetraacetic acid (EDTA) or MTAD. STUDY DESIGN: In total, 45
      maxillary incisor teeth were randomly divided into 2 different irrigation groups
      of 20 canals each and a negative control group of 5 canals. The canals in each of
      the irrigation groups were irrigated using sodium hypochlorite (1.3%) as an
      initial irrigant during the first 2 minutes of operation, followed by 2 minutes
      continuous irrigation with either 17% EDTA or MTAD in a closed system. The
      negative control group was irrigated using 1.3% sodium hypochlorite. The roots
      were split longitudinally and subjected to scanning electron microscopy (SEM).
      The presence of debris and smear layer in the coronal, middle, and apical thirds
      of the canal was evaluated using a 5-grade scoring system with *200 and *2,000
      magnification, respectively. RESULTS: The SAF operation with 2-minute continuous
      irrigation using MTAD resulted in root canal walls that were free of smear layer
      in 85%, 70%, and 60% and of debris in 95%, 90%, and 95% of the coronal, middle,
      and apical thirds of the root canals, respectively. The SAF operation with
      continuous irrigation using EDTA resulted in root canal walls that were free of
      smear layer in 85%, 60%, and 50% and of debris in 95%, 90%, and 85% of the
      coronal, middle, and apical thirds of the root canals, respectively. Teeth in the
      negative control group were totally covered with debris. Evaluation by SEM showed
      no significant difference between the tested irrigants in removing the smear
      layer and debris among the different regions of the root canal. Both groups were
      significantly different from the negative control group. CONCLUSIONS: When using
      the SAF, the protocols used in this study were effective for debridement for all
      regions of the root canal even for the apical thirds.

PMID- 21873087
TI  - Cytocompatibility of new bioceramic-based materials on human fibroblast cells
      (MRC-5).
AB  - OBJECTIVE: The aim of this study was to evaluate and compare the cytotoxicity of
      2 bioceramic-based materials, BioAggregate and iRoot, on human fibroblast MRC-5
      cells. STUDY DESIGN: Twenty-four disks of BioAggregate and iRoot SP materials
      were fabricated (2 * 5 mm). Disks were immersed in cell culture medium at 37
      degrees C for 5 days, and the extracts obtained were diluted with Dulbecco's
      Modified Eagle medium to achieve 5 concentrations (neat, 1/2, 1/10, 1/50, 1/100).
      Human fibroblast cells were incubated with each extract dilution for 24 hours, 72
      hours, and 7 days, then cellular viability was assessed using MTT assay.
      Differences in mean cell viability values between materials were assessed by
      using the 1-way ANOVA and Tukey's test. RESULTS: A statistically significant
      difference was found between the experimental materials and the control group and
      between the 2 materials at the neat, 1/2, 1/10 concentrations for the 3
      incubation periods (P < .001). The cytotoxic effect of both materials was
      concentration dependant. CONCLUSIONS: Both BioAggregate and iRoot SP displayed an
      acceptable biocompatibility.

PMID- 21873088
TI  - Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia
      and lamellar histopathology in Standardbred horses.
AB  - Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the
      role of glucose in the pathogenesis of the disease has not been fully
      investigated. This study aimed to determine the endogenous insulin response to a
      quantity of glucose equivalent to that administered during a laminitis-inducing,
      euglycaemic, hyperinsulinaemic clamp, over 48 h in insulin-sensitive Standardbred
      racehorses. In addition, the study investigated whether glucose infusion, in the
      absence of exogenous insulin administration, would result in the development of
      clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was
      infused intravenously at a rate of 0.68 mL/kg/h for 48 h in treated horses (n=4)
      and control horses (n=3) received a balanced electrolyte solution (0.68 mL/kg/h).
      Lamellar histology was examined at the conclusion of the experiment. Horses in
      the treatment group were insulin sensitive (M value 0.039+/-0.0012 mmol/kg/min
      and M-to-I ratio (100*) 0.014+/-0.002) as determined by an approximated
      hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7+/
      0.78 mmol/L) and hyperinsulinaemia (208+/-26.1 MUIU/mL), whereas control horses
      did not. None of the horses became lame as a consequence of the experiment but
      all of the treated horses developed histopathological evidence of laminitis in at
      least one foot. Combined with earlier studies, the results showed that laminitis
      may be induced by either insulin alone or a combination of insulin and glucose,
      but that it is unlikely to be due to a glucose overload mechanism. Based on the
      histopathological data, the potential threshold for insulin toxicity (i.e.,
      laminitis) in horses may be at or below a serum concentration of ~200 MUIU/mL.

PMID- 21873090
TI  - Comparing fibromyalgia across different clinical settings: is it apples and
      oranges, or oranges and tangerines?

PMID- 21873089
TI  - The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar
      atrophy in children.
AB  - Childhood cerebellar ataxias, and particularly congenital ataxias, are
      heterogeneous disorders and several remain undefined. We performed a muscle
      biopsy in patients with congenital ataxia and children with later onset undefined
      ataxia having neuroimaging evidence of cerebellar atrophy. Significant reduced
      levels of Coenzyme Q10 (COQ10) were found in the skeletal muscle of 9 out of 34
      patients that were consecutively screened. A mutation in the ADCK3/Coq8 gene
      (R347X) was identified in a female patient with ataxia, seizures and markedly
      reduced COQ10 levels. In a 2.5-years-old male patient with non syndromic
      congenital ataxia and autophagic vacuoles in the muscle biopsy we identified a
      homozygous nonsense mutation R111X mutation in SIL1 gene, leading to early
      diagnosis of Marinesco-Sjogren syndrome. We think that muscle biopsy is a
      valuable procedure to improve diagnostic assesement in children with congenital
      ataxia or other undefined forms of later onset childhood ataxia associated to
      cerebellar atrophy at MRI.

PMID- 21873091
TI  - Broad-band homo-nuclear correlations assisted by 1H irradiation for bio-molecules
      in very high magnetic field at fast and ultra-fast MAS frequencies.
AB  - We propose a new broadband second-order proton-assisted (13)C-(13)C correlation
      experiment, SHANGHAI. The (13)C-(13)C magnetization transfer is promoted by (1)H
      irradiation with interspersed four phases super-cycling. This through-space homo
      nuclear sequence only irradiates on the proton channel during the mixing time.
      SHANGHAI benefits from a large number of modulation sidebands, hence leading to a
      large robustness with respect to chemical shift differences, which permits its
      use in a broad MAS frequency range. At ultra-fast MAS (nu(R) 60 kHz), SHANGHAI is
      only efficient when the amplitude of (1)H recoupling rf-field is close to half
      the spinning speed (nu(1) ~ nu(R)/2). However, at moderate to fast MAS (nu(R)=20
      35 kHz), SHANGHAI is efficient at any rf-power level larger than nu(1) ~ 10 kHz,
      which simultaneously permits avoiding excessive heating of bio-molecules, and
      using large sample volumes. We show that SHANGHAI can be employed at the very
      high magnetic field of 23.5 T and then allows the observation of correlation
      between (13)C nuclei, even if their resonance frequencies differ by more than 38
      kHz.

PMID- 21873092
TI  - A clinical comparison of remifentanil or alfentanil in propofol-anesthetized cats
      undergoing ovariohysterectomy.
AB  - Sixteen cats were used to compare the cardiovascular and anesthetic effects of
      remifentanil (REMI) or alfentanil (ALF) in propofol-anesthetized cats undergoing
      ovariohysterectomy. After premedication with acepromazine, anesthesia was induced
      and maintained with a constant rate infusion of propofol (0.3 mg/kg/min). REMI or
      ALF infusions were administered simultaneously with propofol. Heart rate (HR),
      systolic arterial pressure (SAP), pulse oximetry (SpO(2)), rectal temperature
      (RT), and response to surgical stimulation were recorded at predefined time
      points during anesthesia. Data [mean+/-standard deviation (SD)] were analyzed by
      analysis of variance (ANOVA) for repeated measures followed by a Dunnett's test
      and Student t-test (P<0.05). SAP was significantly lower in ALF group than in
      REMI group. Extubation time was significantly shorter in REMI than in ALF group.
      Overall infusion rate of REMI and ALF was 0.24+/-0.05 MUg/kg/min and 0.97+/-0.22
      MUg/kg/min, respectively. The combination of propofol and REMI or ALF provided
      satisfactory anesthesia in cats undergoing ovariohysterectomy.

PMID- 21873093
TI  - Isolation of multiple nontuberculous mycobacteria species in the same patients.
AB  - BACKGROUND: During the observation of many patients with nontuberculous
      mycobacteria (NTM) infections, we have often isolated different NTM species in
      the same patient. In this study we elucidated the patterns of multiple NTM
      species isolation. METHODS: The analysis included all patients from whom more
      than one species of mycobacteria were cultured from a respiratory specimen at
      Seoul National University Hospital, a tertiary referral hospital in South Korea,
      between January 2002 and December 2008. The demographic characteristics and
      clinical and radiographic findings were reviewed retrospectively. RESULTS:
      Multiple NTM species were isolated from 37 patients. Four patients with
      Mycobacterium gordonae, Mycobacterium terrae, or Mycobacterium lentiflavum were
      excluded due to the possibility of contamination. Transition to another NTM
      species was observed in 23 patients (69.7%), while alternating isolation of two
      or three NTM species was seen in nine patients. Two species were isolated
      simultaneously from different sputum samples collected from one patient on the
      same day. CONCLUSIONS: Different NTM species were isolated from the same
      patients.

PMID- 21873094
TI  - [Intensity modulated radiation therapy for head and neck cancer: The standard].
AB  - Combined radical radiation therapy for head and neck carcinoma should be planned
      with intensity modulated beams to provide a rapid answer to patients'
      requirements in terms of quality of treatment. The most frequent late toxicity of
      radiation therapy is xerostomia, which may be prevented by using this technique
      able to significantly spare salivary glands irradiation. Selection of indications
      is a very important step. The objective of sparing salivary functions, strongly
      associated with optimization criteria of quality of life should be considered as
      a main objective in irradiation of head and neck tumours. The various
      possibilities offered by this technique allowing to boost a target volume
      included in prophylactically irradiated regions could offer the possibility to
      escalate the dose in selected patients. The feasibility of this process is
      currently validated in prospective studies. Finally, routine implementation of
      intensity modulated radiation therapy should be performed with strong and robust
      quality assurance procedures, ensuring that the expected benefit could be
      increased with the current developments by using rotational techniques.

PMID- 21873095
TI  - [Debate: Pro intraoperative radiation therapy in breast cancer].
AB  - The use of intraoperative radiation therapy in breast cancer patients started
      about 20 years ago. Several retrospective and prospective studies have been
      published. Intraoperative radiation therapy was initially given as a boost to the
      tumour bed, followed by whole-breast irradiation. These studies have demonstrated
      the feasibility of the technique, with local control rates and cosmetic results
      similar to those obtained with standard treatments. Accelerated partial breast
      irradiation yields local recurrence rates as low as those observed after whole
      breast irradiation. Intraoperative radiation therapy as a single irradiation
      modality with a unique dose has been investigated in recent prospective studies
      showing satisfactory local results. Intraoperative radiation therapy can be
      proposed either as a boost or as a unique treatment in selected cases (tumour
      size, nodal and hormonal status, patient's age). Intraoperative radiation therapy
      can be delivered by orthovoltage (50 kV) X-rays from mobile generators, or by
      electrons from linear accelerators, mobile or fixed, dedicated or not to
      intraoperative radiation therapy.

PMID- 21873096
TI  - [Radiotherapy of lung cancer: Any room left for elective mediastinal irradiation
      in 2011?].
AB  - Traditionally, the target volumes of curative-intent radiotherapy for non-small
      cell lung cancer include all uninvolved mediastinal nodes. However, an
      improvement in tumour control requires an increase of the total dose to the
      macroscopic target volume. This is only achievable if the irradiation of the
      organs at risk is reduced, i.e. elective irradiation of the mediastinum is
      omitted. The available data suggest that elective mediastinal irradiation may be
      safely omitted, provided that an adequate staging procedure, including FDG PET
      CT, has been performed.

PMID- 21873097
TI  - [Does persistent occiput posterior position increase the risk of severe perineal
      laceration?].
AB  - OBJECTIVE: To assess the risk of severe perineal lacerations (III and IV degrees)
      during vaginal deliveries in occiput posterior position. PATIENTS AND METHODS: We
      conducted a retrospective cohort study of 9097 vaginal deliveries in a teaching
      hospital's maternity between January 1st 2005 and December 31st 2008. Risk
      factors associated with tears of the 3rd or 4th degree were studied by a
      multivariate logistic regression. RESULTS: Severe perineal lacerations occurred
      in 1.69% of cases (n=152) and did not significantly vary between 2005 and 2008.
      Parity was a protective factor (OR 0.42; P<0.001; IC(95%) 0.29-0.60) whereas
      instrumental extraction was associated with an increased risk: vacuum (OR 3.95;
      P<0.001, IC(95%) 2.23-7.00) and forceps (OR 3.55; P<0.001, IC(95%) 2.33-5.42).
      macrosomia. Risks were also increased in fetal macrosomia and episiotomy did not
      protect the mother (respectively OR 1.41 P<0.001, IC(95%) 1.19-1.68 and OR 1.73;
      P<0.001, IC(95%) 1.16-2.57). Persistent occiput posterior position was not
      significantly associated with an anal sphincter injury (OR=1.70 P=0.059; IC(95%)
      0.98-2.94). DISCUSSION AND CONCLUSION: In our series, occiput posterior position
      did not significantly impact the risk of severe perineal laceration. A manual
      rotation of the fetal head should be performed in case of associated risk
      factors.

PMID- 21873098
TI  - [Sentinel lymph node detection in patients with early-stage breast cancer: which
      site of injection in 2011?].
AB  - Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of
      choice for axillary staging of breast cancer. Several methods have been developed
      to identify SLNs, including peritumoral or periareolar injection of blue dye or
      technetium colloid. The optimal site for injection of mapping tracers is
      controversial in SLN. The peritumoral injection provides information on the deep
      lymphatic drainage and the internal mammary chain. The advantages of periareolar
      injection are simplicity, the ability to perform it in non-palpable tumors, and
      the potential enhancement of uptake via the subareolar lymphatic plexus. The
      results of multiinstitutional study have indicated that superficial injection
      (periareolar or peritumoral) is associated with a better identification rate and
      an equal false-negative rate compared to deep peritumoral (PT) injection.
      However, the false-negative rate of periareolar injection has not been formally
      demonstrated.

PMID- 21873099
TI  - Sonochemical efficiency dependence on liquid height and frequency in an improved
      sonochemical reactor.
AB  - The aim of this study was to evaluate the effects of liquid height and frequency
      on sonochemical efficiency of a cup-horn sonoreactor. The selected frequencies
      (22, 371, 504 kHz) and liquid height (29-348 mm) were applied while measuring
      acoustic yield, I(3)(-) formation rate and the resulting sonochemical efficiency.
      The frequency effect was shown to be coupled to liquid height effect. Indeed,
      acoustic zones (i.e. Fresnel and Fraunhofer zones), which limits depends on both
      transducer diameter and frequency, significantly determine the production of
      radicalar species quantified by I(3)(-) formation rate. An increase of ultrasonic
      frequency results in lower acoustic yield and higher sonochemical efficiency.
      Theoretical physical and chemical effects attributed to collapsing bubbles were
      considered. Sonochemical efficiencies obtained at 500 kHz were similar or higher
      than those at 371 kHz, depending on liquid height. The effect of reactor
      configuration was further investigated as an hypothesis to explain unsignificant
      effect of standing waves in our study. Therefore, the dependence of sonochemical
      efficiency with liquid height might be firstly attributed to reactor
      configuration prior to frequency effects.

PMID- 21873100
TI  - Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes.
AB  - BACKGROUND: Clinical differentiation between parkinsonian syndromes (PS) remains
      a challenge despite well-established clinical diagnostic criteria. Specific
      diagnostic biomarkers have yet to be identified, though in recent years, studies
      have been published on the aid of certain brain related proteins (BRP) in the
      diagnosing of PS. We investigated the levels of the light subunit of
      neurofilament triplet protein (NF-L), total tau and phosphorylated tau, amyloid
      beta(1-42), and the soluble alpha- and beta-cleaved fragments of amyloid
      precursor proteins in a cohort of patients with various PS. METHODS: Seventy-one
      patients with different PS and cerebellar disorders were included consecutively
      over 21 months. CSF was collected at inclusion. Clinical follow-up was performed
      after 16 months (median; range: 9-30). Statistical comparison was performed after
      follow-up on 53 patients in four subgroups of PS: multiple system atrophy (MSA)(n
      = 10), progressive supranuclear palsy (PSP)(n = 10), dementia with Lewy bodies
      (DLB)(n = 11), and Parkinson's disease (PD)(n = 22), using the non-parametric
      Kruskal-Wallis test. RESULTS: A statistically significant difference was found
      for NF-L (p < 0.0001, lowest values for PD), Abeta(1-42,) (p = 0.002, lowest
      values for DLB), and sAPPalpha and sAPPbeta (p = 0.03 and 0.02, lower values
      observed for DLB and MSA). CONCLUSION: We demonstrate a potential role for
      sAPPalpha and sAPPbeta in distinguishing between PS, a finding that needs to be
      confirmed in future studies of larger cohorts. There is a tendency towards low
      levels of Abeta(1-42) in DLB patients in our cohort. Further, our results support
      findings from previous studies, which indicate an ability to separate atypical PS
      from PD based on levels of NF-L.

PMID- 21873101
TI  - Parkinsonism and dropped head: dystonia, myopathy or both?
AB  - BACKGROUND: Dropped head syndrome (DHS) occurring with parkinsonism is often
      suggested to be a clue to multiple system atrophy (MSA), but it may occur in
      other parkinsonian conditions. The substrate for DHS is controversial, with some
      concluding that the cause is myopathic and others, exclusively dystonic. We
      report our clinical series of DHS arising in the setting of parkinsonism.
      METHODS: Patients with DHS were initially identified by a retrospective computer
      search of the Mayo Clinic (Rochester, MN) medical record database from January
      1997 to July 2010. Subsequent record review confirmed DHS and documented those
      with parkinsonism. RESULTS: We identified 21 patients with DHS and parkinsonism,
      12 male, 9, female. The median age of DHS onset was 69 years (interquartile
      range: 63.6-77.5 years). This included 10 patients with Parkinson's disease (PD),
      10 with MSA, and 1 with drug-induced parkinsonism. The DHS component of their
      disorder segregated into three different subgroups: dystonia-alone (12 patients);
      myopathy-alone (4 patients; focal cervical myopathy in 3 and generalized myopathy
      in one); coexisting dystonia and myopathy (5 patients; 3 generalized, 2 focal
      cervical myopathy). CONCLUSIONS: DHS may be seen in either MSA or PD. It may be
      due to myopathy, dystonia or both. In some cases, the myopathy was focal,
      confined to the neck musculature. Whether dystonic antecollis predisposes to
      local muscle pathology is open to speculation.

PMID- 21873102
TI  - Longitudinal relation of community-level income inequality and mortality in Costa
      Rica.
AB  - The controversy regarding the direct relationship between income distribution and
      health remains unresolved. Empirical evidence has often failed to advance our
      understanding because in the countries studied there was limited ability to
      distinguish hypotheses. This study examines the relation between inequality and
      mortality in the context of Costa Rica. Costa Rica's unique social and political
      structure makes confounding through resource and political channels less likely,
      thus any effects would work predominantly through direct psychosocial channels.
      Using mortality data extracted from the Vital Statistics Registry, we evaluate
      the longitudinal relations between lagged and contemporaneous income inequality
      and cause-specific mortality in Costa Rica from 1995 to 2005. For those aged 15
      60, results indicate that there is a significant adverse relation between
      increases in lagged inequality and mortality from liver disease, and marginal
      adverse relations with mortality from diabetes and suicide. For those aged 60 and
      over, there is a limited evidence of a relation between inequality and health.
      These results suggest increases in inequality may impact health behavior of the
      working aged population in Costa Rica.

PMID- 21873103
TI  - "Getting sicker quicker": does living in a more deprived neighbourhood mean your
      health deteriorates faster?
AB  - Data from the longitudinal West of Scotland Twenty-07 STUDY: Health in the
      Community was used to examine whether, over a 20 year period, the self-reported
      health of people living in deprived areas became poorer faster compared to those
      living in more affluent areas. Three cohorts (born in the early 1930s, 1950s and
      1970s) are included, covering 60 years of the life span. Using multilevel growth
      curve models, a 40% probability of reporting poor health was predicted among
      residents of more deprived areas at an earlier age (66) compared to those living
      in more affluent areas (83). Wider area differences were seen for men than for
      women. Our findings indicate that attempts to reduce area differences in health
      should start young but also continue throughout the lifespan.

PMID- 21873104
TI  - Morphological appearance manifolds for group-wise morphometric analysis.
AB  - Computational anatomy quantifies anatomical shape based on diffeomorphic
      transformations of a template. However, different templates warping algorithms,
      regularization parameters, or templates, lead to different representations of the
      same exact anatomy, raising a uniqueness issue: variations of these parameters
      are confounding factors as they give rise to non-unique representations.
      Recently, it has been shown that learning the equivalence class derived from the
      multitude of representations of a given anatomy can lead to improved and more
      stable morphological descriptors. Herein, we follow that approach, by
      approximating this equivalence class of morphological descriptors by a
      (nonlinear) morphological appearance manifold fitting to the data via a locally
      linear model. Our approach parallels work in the computer vision field, in which
      variations lighting, pose and other parameters lead to image appearance manifolds
      representing the exact same figure in different ways. The proposed framework is
      then used for group-wise registration and statistical analysis of biomedical
      images, by employing a minimum variance criterion to perform manifold-constrained
      optimization, i.e. to traverse each individual's morphological appearance
      manifold until group variance is minimal. The hypothesis is that this process is
      likely to reduce aforementioned confounding effects and potentially lead to
      morphological representations reflecting purely biological variations, instead of
      variations introduced by modeling assumptions and parameter settings.

PMID- 21873105
TI  - Factors predicting survival after diagnosis of laryngeal cancer.
AB  - Survival in patients with laryngeal cancer has not increased remarkably within
      the last years. It is presumed that a variety of factors act jointly in
      predicting survival after diagnosis: tumour stage, tumour site, treatment
      approaches, age and comorbidities. The aim of this German clinical multi-centre
      study is to present results from multivariate analysis. A retrospective cohort
      study was conducted in four hospitals in South-West Germany. Incident cases with
      laryngeal squamous cell carcinoma were included for the years 1998 to 2004,
      resulting in a population sample of 594 patients. Multivariate regression
      analysis was performed using the Cox proportional hazards model. Patients were
      followed up for 64.1months on average. Overall 5-year survival was 66% (95%
      confidence interval (CI): 62-70%). The strongest risk factors in multivariate
      analysis were age at first diagnosis (hazard ratio (HR): 1.5; 95% CI: 1.5-1.7 per
      each additional 10years), tumour stage, and the development of recurrences (HR
      3.1; 95% CI: 2.3-4.2) or second primary carcinomas (HR 2.1; 95% CI: 1.4-3.1). A
      somewhat weaker effect was shown for patients with comorbidities (using
      Charlson's comorbidity index). The choice of treatment did not strongly affect
      survival when adjusting for other factors, possibly because the optimal treatment
      approach was applied for the specific constitution and requirements of each
      patient. For future research it would be desirable to study the effect of
      treatment on quality of life in multivariate analysis as well as other modifiable
      risk factors as smoking and drinking reduction or cessation after diagnosis.

PMID- 21873106
TI  - Dental implant placement after mandibular reconstruction by microvascular free
      fibula flap: current knowledge and remaining questions.
AB  - Mandibular reconstruction by microvascular free fibula flap has dramatically
      improved the quality of life of patients treated by interruptive surgery. A
      simple prosthesis can be used for dental rehabilitation but in many cases, these
      prostheses remain nonfunctional. The use of osseointegrated implants restores
      both function and aesthetics. The technique for implantation in fibula flap is
      very similar to the technique in native mandible but access to the bone is the
      most difficult step of the surgery. The success rate for osteointegration ranges
      from 86% to 99% but the success rate of the prosthesis is much lower. This
      difference could be explained by the vertical discrepancy between the graft and
      the remaining mandible, which leads to an unfavourable implant-crown ratio. The
      quality of soft tissues is also a limiting factor for the prosthesis, and
      hypertrophy often appears after the placement of the abutments. The type of the
      prosthesis (fixed or removable) should also be discussed. Occlusal considerations
      should be highlighted as occlusion remains abnormal in many cases. Three
      dimensional imaging might help in the planning of these complex reconstructions.
      A close collaboration between the maxillo-facial surgeon, the oral surgeon and
      the prosthodontist is necessary to obtain good results.

PMID- 21873107
TI  - The antibiotic R&D pipeline: an update.
AB  - There is an urgent need for new antibacterials to target emerging multidrug
      resistant bacteria. The need for such agents is rising while the efforts in
      antibacterial research have declined dramatically in the past few decades with
      the result of only four compounds belonging to new chemical classes being
      approved for clinical use. The main reasons that led to this critical situation
      are shortly described. A renewed interest in the research of new effective
      antimicrobials is nonetheless delivering compounds deriving mainly from
      modification of existing drugs, yet new chemical classes are appearing. Because
      many of these activities have started relatively recently, we should expect a
      long period before new antibiotics are added to the medical armamentarium.

PMID- 21873108
TI  - Physicochemical studies of some novel Y-shaped imidazole derivatives--a sensitive
      chemisensor.
AB  - Some novel Y-shaped imidazole derivatives were developed for highly sensitive
      chemisensors for transition metal ions. A prominent fluorescence enhancement was
      found in the presence of transition metal ions such as Hg(2+), Pb(2+) and Cu(2+)
      and it is due to the suppression of radiationless transitions from the n-pi*
      state in the chemisensors. The HOMO-LUMO energies, electric dipole moment (MU)
      and the first-hyperpolarizability (beta) values of the investigated molecule have
      been studied theoretically which reveal that the synthesized molecules have
      microscopic non-linear optical (NLO) behaviour with non-zero values.

PMID- 21873109
TI  - An integrated video-analysis software system designed for movement detection and
      sleep analysis. Validation of a tool for the behavioural study of sleep.
AB  - OBJECTIVE: The aim of the present study was to develop and validate a software
      tool for the detection of movements during sleep, based on the automated analysis
      of video recordings. This software is aimed to detect and quantify movements and
      to evaluate periods of sleep and wake. METHODS: We applied an open-source
      software, previously distributed on the web (Zoneminder, ZM), meant for video
      surveillance. A validation study was performed: computed movement analysis was
      compared with two standardised, 'gold standard' methods for the analysis of sleep
      wake cycles: actigraphy and laboratory-based video-polysomnography. RESULTS:
      Sleep variables evaluated by ZM were not different from those measured by
      traditional sleep-scoring systems. Bland-Altman plots showed an overlap between
      the scores obtained with ZM, PSG and actigraphy, with a slight tendency of ZM to
      overestimate nocturnal awakenings. ZM showed a good degree of accuracy both with
      respect to PSG (79.9%) and actigraphy (83.1%); and had very high sensitivity (ZM
      vs. PSG: 90.4%; ZM vs. actigraphy: 89.5%) and relatively lower specificity (ZM
      vs. PSG: 42.3%; ZM vs. actigraphy: 65.4%). CONCLUSIONS: The computer-assisted
      motion analysis is reliable and reproducible, and it can allow a reliable esteem
      of some sleep and wake parameters. The motion-based sleep analysis shows a trend
      to overestimate wakefulness. SIGNIFICANCE: The possibility to measure sleep from
      video recordings may be useful in those clinical and experimental conditions in
      which traditional PSG studies may not be performed.

PMID- 21873110
TI  - The error-related negativity associated with different strength of stimulus
      response interference.
AB  - OBJECTIVE: The present study was aimed at clarifying the effect of stimulus
      response compatibility (SRC) interference on the ERN. METHODS: We compared ERNs
      in two tasks differing in the level of interference, an arrow (AR) task
      classified as a Simon task and a more complex arrow-orientation (AO) task
      classified as a spatial-Stroop task. We also compared ERNs between partial errors
      (with initial incorrect movement corrected by a proper full response) and overt
      (uncorrected) errors. RESULTS: Behavioral response time and error rate indicated
      that both interference and ERN amplitude were larger for the AO task than for the
      AR task. There was no significant difference in the ERN amplitude between the
      partial and overt errors. CONCLUSIONS: The ERN becomes larger as a function of
      the SRC interference. SIGNIFICANCE: Our study presented evidence that the ERN may
      represent response-monitoring associated with the SRC interference.

PMID- 21873111
TI  - Mobile phone emission modulates event-related desynchronization of alpha rhythms
      and cognitive-motor performance in healthy humans.
AB  - OBJECTIVES: It has been shown that electromagnetic fields of Global System for
      Mobile Communications phone (GSM-EMFs) affect human brain rhythms (Vecchio et
      al., 2007, 2010), but it is not yet clear whether these effects are related to
      alterations of cognitive functions. METHODS: Eleven healthy adults underwent two
      electroencephalographic (EEG) sessions separated by 1 week, following a cross
      over, placebo-controlled, double-blind paradigm. In both sessions, they performed
      a visual go/no-go task before real exposure to GSM-EMFs or after a sham condition
      with no EMF exposure. In the GSM real session, temporal cortex was continuously
      exposed to GSM-EMFs for 45 min. In the sham session, the subjects were not aware
      that the EMFs had been switched off for the duration of the experiment. In the
      go/no-go task, a central fixation stimulus was followed by a green (50% of
      probability) or red visual stimulus. Subjects had to press the mouse button after
      the green stimuli (go trials). With reference to a baseline period, power
      decrease of low- (about 8-10 Hz) and high-frequency (about 10-12 Hz) alpha
      rhythms indexed the cortical activity. RESULTS: It was found less power decrease
      of widely distributed high-frequency alpha rhythms and faster reaction time to go
      stimuli in the post- than pre-exposure period of the GSM session. No effect was
      found in the sham session. CONCLUSIONS: These results suggest that the peak
      amplitude of alpha ERD and the reaction time to the go stimuli are modulated by
      the effect of the GSM-EMFs on the cortical activity. SIGNIFICANCE: Exposure to
      GSM-EMFs for 45 min may enhance human cortical neural efficiency and simple
      cognitive-motor processes in healthy adults.

PMID- 21873112
TI  - Coupled effects of light and nitrogen source on the urea cycle and nitrogen
      metabolism over a diel cycle in the marine diatom Thalassiosira pseudonana.
AB  - Diatoms are photoautotrophic organisms capable of growing on a variety of
      inorganic and organic nitrogen sources. Discovery of a complete urea cycle in
      diatoms was surprising, as this pathway commonly functions in heterotrophic
      organisms to rid cells of waste nitrogen. To determine how the urea cycle is
      integrated into cellular nitrogen metabolism and energy management, the centric
      diatom Thalassiosira pseudonana was maintained in semi-continuous batch cultures
      on nitrate, ammonium, or urea as the sole nitrogen source, under a 16: 8 light:
      dark cycle and at light intensities that were low, saturating, or high for
      growth. Steady-state transcript levels were determined for genes encoding enzymes
      linked to the urea cycle, urea hydrolysis, glutamine synthesis, pyrimidine
      synthesis, photorespiration, and energy storage. Transcript abundances were
      significantly affected by nitrogen source, light intensity and a diel cycle. The
      impact of N source on differential transcript accumulation was most apparent
      under the highest light intensity. Models of cellular metabolism under high light
      were developed based on changes in transcript abundance and predicted enzyme
      localizations. We hypothesize that the urea cycle is integrated into nitrogen
      metabolism through its connection to glutamine and in the eventual production of
      urea. These findings have important implications for nitrogen flow in the cell
      over diel cycles at surface ocean irradiances.

PMID- 21873113
TI  - Immunoproteomic analysis of the human antibody response to natural tularemia
      infection with Type A or Type B strains or LVS vaccination.
AB  - Francisella tularensis is pathogenic for many mammalian species including humans,
      causing a spectrum of diseases called tularemia. The highly virulent Type A
      strains have associated mortality rates of up to 60% if inhaled. An attenuated
      live vaccine strain (LVS) is the only vaccine to show efficacy in humans, but
      suffers several barriers to licensure, including the absence of a correlate of
      protection. An immunoproteomics approach was used to survey the repertoire of
      antibodies in sera from individuals who had contracted tularemia during two
      outbreaks and individuals from two geographical areas who had been vaccinated
      with NDBR Lot 11 or Lot 17 LVS. These data showed a large overlap in the
      antibodies generated in response to tularemia infection or LVS vaccination. A
      total of seven proteins were observed to be reactive with 60% or more sera from
      vaccinees and convalescents. A further four proteins were recognised by 30-60% of
      the sera screened. These proteins have the potential to serve as markers of
      vaccination or candidates for subunit vaccines.

PMID- 21873114
TI  - Global malaria maps and climate change: a focus on East African highlands.

PMID- 21873115
TI  - To validate: is it so simple?

PMID- 21873116
TI  - Management of female anterior perineal injuries with urethrovaginal disruption by
      anterior sagittal transanorectal approach.
AB  - OBJECTIVE: Urethrovaginal disruption injury poses a considerable challenge in
      surgical correction, mainly due to difficult access to the receded urethrovaginal
      unit deep in the scarred anterior perineum. We assessed the feasibility, safety
      and efficacy of the anterior sagittal transanorectal approach (ASTRA) in the
      repair of anterior perineal injury with urethrovaginal disruption in female
      children. MATERIALS AND METHODS: Three girls with urethrovaginal disruption
      following perineal injury were operated by ASTRA between March 2008 and December
      2010. All of them had severe scarring of the anterior perineum at the time of
      definitive repair by this approach. One underwent ASTRA repair without a covering
      colostomy. RESULTS: Total urethrovaginal mobilization and anchorage of urethral
      and vaginal orifices at the vestibule were successfully achieved in all patients.
      One patient has developed vaginal stenosis at 1.5 years follow up. Despite the
      absence of a colostomy cover in one case, there were no wound complications in
      the early postoperative period. CONCLUSION: The ASTRA is safe and efficacious in
      the repair of traumatic urethrovaginal disruption in children.

PMID- 21873117
TI  - Analysis of bulk and virus-specific CD8+ T cells reveals advanced differentiation
      of CD8+ T cells in patients with common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency
      syndrome with alterations in T cell regulation and function in a subgroup of
      patients. We assessed phenotype and function of bulk and virus-specific CD8+ T
      cells of a cohort of 34 HLA-A2+ CVID patients by pentamer technology and flow
      cytometry in relationship to their immunological and clinical phenotypes. Bulk
      CD8+ T cells displayed a shift toward a more antigen experienced and activated
      differentiation state. The advanced differentiation pattern was mainly found in a
      subgroup of CVID patients with lymphadenopathy and granulomatous disease. This
      effect existed independently of the patients' CMV status even so CMV-associated
      immunosenescence was more evident in CVID patients than in CMV-positive
      immunocompetent controls. As the phenotype and function of virus-specific CD8+ T
      cells were normal in CVID the induction of antiviral immunity by prophylactic
      immunization appears to be a logical and desirable aim for this group of
      patients.

PMID- 21873118
TI  - The decidual gamma-delta T cells up-regulate the biological functions of
      trophoblasts via IL-10 secretion in early human pregnancy.
AB  - The functions of decidual gammadeltaT cells in early human pregnancy are not
      fully understood. The present study was undertaken to characterize the action of
      decidual gammadeltaT cells, and analyze their regulatory roles in proliferation
      and invasion of trophoblasts in early human pregnancy. It was revealed that
      decidual gammadeltaT cells were a CD4(-) and CD8(-) subset whose numbers
      increased significantly in either the decidua or peripheral blood. The main
      cytokines synthesized in decidual gammadeltaT cells in decreasing concentration
      were; IL-10>TGF-beta>TNF-alpha>=IFN-gamma, with little IL-2 or IL-4 being
      produced. Decidual gammadeltaT cells promoted trophoblast proliferation and
      invasion, and suppressed trophoblast apoptosis through IL-10 secretion in co
      culture. These results suggest that gammadeltaT cells in human decidua might play
      an important role in the Th2 bias at maternal-fetal interface and in the
      development and progression of the placenta, which is beneficial to maternal
      immunotolerance toward the fetus in early human pregnancy.

PMID- 21873119
TI  - Early-life seizures produce lasting alterations in the structure and function of
      the prefrontal cortex.
AB  - Early-life seizures (ELS) are associated with long-term behavioral disorders
      including autism and ADHD, suggesting that frontal lobe structures may be
      permanently affected. We tested whether ELS produce structural alterations in the
      prefrontal cortex (PFC) and impair PFC-mediated function using an operant task of
      behavioral flexibility in rats. Adult rats that had been exposed to 75 flurothyl
      seizures during postnatal days 1-10 showed decreased behavioral flexibility in
      the task compared to controls over multiple behavioral sessions, measured as a
      lever preference asymmetry (p<0.001) and a decreased efficiency of attaining food
      rewards (p<0.05). ELS rats also showed an increased thickness of the PFC
      (p<0.01), primarily attributed to layer V (p<0.01) with no differences in cell
      density. These structural changes correlated with lever preference behavioral
      impairments (p<0.05). This study demonstrates that the consequences of ELS extend
      to the PFC, which may help explain the high prevalence of comorbid behavioral
      disorders following ELS.

PMID- 21873120
TI  - Spatial navigation impairment in patients with refractory temporal lobe epilepsy:
      evidence from a new virtual reality-based task.
AB  - This study was aimed at examining spatial learning and memory in nonoperated
      temporal lobe epilepsy (TLE). Twenty-five patients with a refractory epileptic
      focus located in the temporal lobe (10 in the right hemisphere and 15 in the left
      hemisphere) and 25 healthy age-matched controls performed the "Boxes Room," a
      virtual reality version of the holeboard. They were trained in 10 trials to
      locate the reward boxes in a room with 16 of them available. Participants also
      completed a comprehensive neuropsychological evaluation. Patients performed
      significantly worse relative to the control group. They traveled longer distances
      and committed more errors than controls. No differences in performance were found
      within the TLE group when gender or lateralization of the epileptic focus was
      considered an independent variable. These findings suggest that the integrity of
      temporal structures in both hemispheres could be critical to spatial learning and
      memory and support the spatial component of the task.

PMID- 21873121
TI  - Peripapillary subretinal neovascular membranes: a review.
AB  - Peripapillary subretinal neovascular membranes (PSRNVM) are most commonly
      associated with age-related macular degeneration and idiopathic causes in older
      patients. In younger patients, the condition has been linked to a wide variety of
      other conditions. As with the more commonly occurring macular form of choroidal
      neovascular membranes, PSRNVM can also lead to severe vision loss. Therefore,
      clinicians must take care to avoid overlooking this event to provide appropriate
      management and treatment. Current knowledge of PSRNVM suggests the importance of
      regular examinations of the affected eye in both treated and untreated cases to
      watch for progression and recurrence, which are unpredictable, and also of the
      fellow eye because there is a high risk of bilateral involvement.

PMID- 21873122
TI  - Matrix solid-phase dispersion extraction coupled with HPLC-diode array detection
      method for the analysis of sesquiterpene lactones in root of Saussurea lappa
      C.B.Clarke.
AB  - We developed a reliable and effective method to determine costunolide and
      dehydrocostuslactone in the root of Saussurea lappa C. B.Clarke using matrix
      solid-phase dispersion (MSPD) extraction, HPLC separation and diode array
      detection (DAD). Several extraction parameters for the MSPD were optimized.
      Florisil was chosen as dispersing adsorbent with methanol as elution solvent. The
      ratio of Florisil to sample was selected to be 4:1 and no additional clean-up
      steps were needed. Linearities (r>0.9995) were determined to be in the range of
      22.5-360.0 MUg/mL for costunolide and 25.0-400.0 MUg/mL for dehydrocostuslactone.
      Intra- and inter-day precisions were also determined with a relative standard
      deviation (RSD) less than 3.2%. The limits of detection were found to be 0.122
      MUg/mL for costunolide and 0.135 MUg/mL for dehydrocostuslactone. The recoveries
      were in the range of 92.5-99.8% with relative standard deviations ranged from
      1.2% to 3.5%. The proposed MSPD method required shorter time and lower solvent
      volume than maceration-ultrasonic and Soxhlet extraction methods.

PMID- 21873123
TI  - Microchip fluorescence-enhanced immunoaasay for simultaneous quantification of
      multiple tumor markers.
AB  - A microchip fluorescence-enhanced immunoassay method was developed for
      simultaneous detection of carcinoma antigen 125 (CA125) and carbohydrate antigen
      15-3 (CA15-3). In this method, CA125 and CA15-3 react with excess amount of
      fluorescein isothiocyanate (FITC)-labeled monoclonal antibodies (Ab(*)) of CA125
      and CA15-3 to form CA125-Ab(125)(*) and CA15-3-Ab(15-3)(*) complexes. Microchip
      electrophoresis (MCE) separation of free Ab(125)(*), Ab(15-3)(*), and CA125
      Ab(125)(*), CA15-3-Ab(15-3)(*) complexes were then performed. The separated
      species were sensitively detected by laser-induced fluorescence detection (LIF).
      CA125 and CA15-3 were quantified simultaneously by measuring the fluorescence
      intensity of CA125-Ab(125)(*) and CA15-3-Ab(15-3)(*) complexes, respectively.
      Under the optimum conditions, the limits of detection were 0.23 U/mL for CA125
      and 0.09 U/mL for CA15-3. The present MCE-LIF method was applied to the
      determination of CA125 and CA15-3 in serum from healthy subjects and cancer
      patients. The levels of CA125 and CA15-3 in these sera samples were found to be
      in the ranges of 15.6-36.1 U/mL and 13.8-28.4 U/mL for healthy subjects, and
      192.5-368.3 U/mL and 63.3-198.4 U/mL for cancer patients.

PMID- 21873124
TI  - Scarlet fever outbreak in Hong Kong, 2011.

PMID- 21873125
TI  - [Vascular malformation of the knee simulating juvenile idiopathic arthritis].

PMID- 21873126
TI  - Representations of celebrities' weight and shape during pregnancy and postpartum:
      a content analysis of three entertainment magazine websites.
AB  - Entertainment magazine websites provide a continuous stream of celebrity news
      accessed by over 13 million unique viewers each month. Celebrities' experiences
      of pregnancy and new motherhood appear to be popular topics within these media
      outlets; however, little research has investigated the content of this coverage.
      In this study, investigators coded articles (N=387) published between August 1,
      2007 and August 1, 2008 on three popular entertainment magazine websites.
      Relatively few articles about celebrities' pregnancies discussed weight (13%) or
      shape (30%), and an even smaller proportion (6.2%) included any discussion of
      postpartum body dissatisfaction. This suggests a gap between portrayal of
      celebrities' pregnancies and postpartum experiences and those of non-celebrity
      women. This disparity is concerning as it might lead to unrealistic expectations
      about pregnancy and postpartum for both pregnant readers and a more general
      audience. This study provides important initial information about the messages
      these media provide regarding pregnancy-related appearance.

PMID- 21873127
TI  - The cost utility of reduction mammaplasty at medium-term follow-up: a prospective
      study.
AB  - PURPOSE: The effects of reduction mammaplasty (RM) have been proved in several
      randomised trials. However, publications regarding cost utility are infrequent
      and lacking with regard to medium-term follow-up. Therefore, we decided to assess
      the cost utility of RM at 2-5 years' follow-up, when later costs and possible re
      operations have been incurred. METHODS: A total of 73 patients had bilateral RM
      between January 2005 and March 2007 in the Hospital District of Helsinki and
      Uusimaa, Finland. Health-related quality of life was measured with the 15D.
      Preoperative data were collected with an interview at an appointment and follow
      up data by means of a postal survey. Direct hospital costs were obtained from the
      Ecomed((r)) clinical patient administration database (Datawell Ltd., Espoo,
      Finland). RESULTS: A total of 62 (85%) patients agreed to participate in the
      study and returned the follow-up questionnaire. The mean follow-up time was 4.0
      years (SD 0.53, range 2.3-4.6 years). The mean improvement in the 15D score
      change was 0.083 (SD 0.081). The mean number of quality-adjusted life years
      (QALYs) gained was 3.052 (SD 3.167, range 2.561-17.553). The mean hospital costs
      of the intervention were ?3601 (SD 1321), and the mean cost per QALY gained was
      ?1180. Roughly 76% of the costs were due to the hospital stay during the
      operation. Eight percent of the costs were incurred more than 6 months after the
      hospital stay. CONCLUSIONS: The cost per QALY gained by RM is low, even when
      considering later costs caused by possible re-operations, and compares favourably
      with a number of other surgical procedures.

PMID- 21873128
TI  - A simple way for salvage of zone IV deep inferior epigastric perforator flap
      using pre-tie sutures and serial delayed closure.

PMID- 21873129
TI  - A third degree burn to one side of the neck associated with episodes of
      bradycardia and asystole.

PMID- 21873130
TI  - A well vascularised muscle flap--drug user's dream.
AB  - It is estimated that worldwide, 16 million people, aged 15-64 years inject
      illicit drugs regularly. When peripheral venous access becomes obliterated, drug
      users start injecting into the subdermal area of the skin - "skin popping". When
      this area ulcerates, the well vascularised granulation tissue called a "shooter's
      patch" is maintained as a portal for continuing injection. These "shooter's
      patches" are usually on the limbs, but have been reported on the breast and the
      penis. We present a case of a reconstructive muscle flap being used in an
      unforeseen manner as a shooters patch. Surgeons rely on muscle flaps to provide a
      robust reconstructive option, but we have learnt that drug users value them for
      their rich vascularity and high absorption.

PMID- 21873131
TI  - The use of Medpor(c) alloplastic material in rhinoplasty: experience and
      outcomes.
AB  - Surgeons often avoid the use of alloplastic materials in functional rhinoplasty
      due to potential complications. The aim of the present study is to present the
      outcomes following the use of alloplastic materials in a large series of
      patients, to identify and document the possible complications and to offer
      insight regarding the safety and the indications of the method. MATERIALS AND
      METHOD: Between February 2005 and August 2009, 58 patients underwent functional
      rhinoplasty using Medpor((r)) alloplastic materials by a single surgeon (A.S).
      The majority of the alloplastic materials were used to reconstruct defects of the
      nasal dorsum as well as to augment the columella and support the nasal tip.
      RESULTS: Medpor((r)) was used in the nasal dorsum in eight patients and in the
      columella in 50 patients. There were 10 cases of primary and 48 cases of
      secondary rhinoplasty. Follow-up time ranged from 1 to 5 years (mean: 3 years).
      Complications concerned three cases of postoperative infection and material
      rejection. All cases were successfully re-operated. CONCLUSION: The use of
      Medpor((r)) alloplastic material in functional rhinoplasty comprises a safe
      method in selected patients due to the low complication rate, as shown in our
      series. It could therefore be considered as a useful alternative when
      reconstruction is problematic due to low quality or lack of available autologous
      grafts.

PMID- 21873132
TI  - Myocutaneous propeller flap based on the superior gluteal artery (SGA) for
      closure of large lumbosacral meningomyelocoele defects: a case report.
AB  - Early and reliable closure of large meningomyelocoele defects in newborns is
      critical to prevent severe infectious complications and neurologic deterioration.
      Here, we introduce a new surgical method for the reconstruction of large
      horizontal meningomyelocoele defects, in which we use unilateral myocutaneous
      tissue based on the superior gluteal artery (SGA) as a propellar flap. This
      procedure permits a tension-free and durable multilayer closure of difficult,
      large-scale horizontal defects that cannot adequately be treated by conventional
      myocutaneous advancement flaps. The technique is reliable and straightforward and
      requires no skin grafts or relaxing incisions. The SGA-based myocutaneous
      propeller flap might be a promising alternative for complex meningomyelocoele
      reconstructions in the future.

PMID- 21873133
TI  - Staged reconstruction of the lower eyelid following tri-lamellar injury: a case
      series and anatomic study.
AB  - PURPOSE: Lower eyelid scaring and malposition following violation of all three
      lamellae pose a significant ophthalmologic reconstructive challenge. The purpose
      of our study was to document a staged approach for this problem using: 1)
      transconjunctival scar release followed by palatal graft below the tarsal plate
      and subciliary scar release followed by full-thickness skin graft superficial to
      the tarsal plate and 2) subsequent autologous fat grafting to the lower eyelid.
      METHODS: Cadaveric anatomic dissections were performed. Post-traumatic and post
      surgical lower eyelid deformities requiring reconstruction were reviewed and
      outcome assessment was based on symptomatic improvement, perioperative
      complications, reoperations and long-term follow-up (> 1 year). RESULTS: Cadaver
      dissections demonstrated consistent lower eyelid tarsal plate and lamellar
      anatomy for the use of palatal graft and skin grafting. Clinically, 75% cases
      resulted from full thickness traumatic laceration of the lower eyelid or malar
      region and 25% of cases occurred after transconjunctival incisions were made for
      zygomatic maxillary repositioning following partial lower eyelid laceration.
      Preoperative symptoms of: epiphora, tearing, redness, blurry vision and dryness
      improved in all patients and complete resolution was seen in 63% of patients.
      Thirty-seven percent of patients had complications: Redundancy of palatal graft,
      Partial FTSG loss, cellulitis after fat transfer. CONCLUSIONS: We describe an
      approach for the scarred and displaced lower eyelid following injury to all three
      lamellae that provided symptomatic improvement after lower lid scar tissue
      release, lengthening of the contracted septum, support of the posterior lamellae
      with a palatal graft and a replacement of anterior lamella with full thickness
      skin graft.

PMID- 21873135
TI  - Anticipating root displacements: unlocking new prospects.
AB  - OBJECTIVE: The aim of this study was to visualize and quantify root displacements
      in the bone base of a patient before orthodontic treatment and obtain an optimal
      set-up that would include information on both coronal and root movements.
      MATERIAL AND METHOD: Data from a patient's scan records, the initial plaster
      model and scanned set-up are migrated into the Amira(r) software for advanced
      mesh and surface analysis. Using this software, each tooth of the initial 3D
      reconstruction scan is isolated then superimposed over that of the initial model.
      The set-up is then positioned onto the initial model at second molar level and
      dragged onto the initial 3D reconstruction. Lastly, the roots are repositioned on
      the crowns on the set-up. RESULTS: This study enabled the visualization and
      quantification of dental displacements (crowns and roots) from initial to
      expected final position in a three-dimensional space reconstruction. DISCUSSION
      CONCLUSION: This technique, carried out routinely thanks to the advent of cone
      beam tomography, can help optimize orthodontic treatments, notably by
      anticipating root proximity issues during set-up preparation.

PMID- 21873136
TI  - Germline mutations of STR-alleles include multi-step mutations as defined by
      sequencing of repeat and flanking regions.
AB  - Well defined estimates of mutation rates are a prerequisite for the use of short
      tandem repeat (STR-) loci in relationship testing. We investigated 65 isolated
      genetic inconsistencies, which were observed within 50,796 allelic transfers at
      23 STR-loci (ACTBP2 (SE33), CD4, CSF1PO, F13A1, F13B, FES, FGA, vWA, TH01, TPOX,
      D2S1338, D3S1358, D5S818, D7S820, D8S1132, D8S1179, D12S391, D13S317, D16S539,
      D17S976, D18S51, D19S433, D21S11) in Caucasoid families residing in Austria and
      Switzerland. Sequencing data of repeat and flanking regions and the median of all
      theoretically possible mutational steps showed valuable information to
      characterise the mutational events with regard to parental origin, change of
      repeat number (mutational step size) and direction of mutation (losses and gains
      of repeats). Apart from predominant single-step mutations including one case with
      a double genetic inconsistency, two double-step and two apparent four-step
      mutations could be identified. More losses than gains of repeats and more
      mutations originating from the paternal than the maternal lineage were observed
      (31 losses, 22 gains, 12 losses or gains and 47 paternal, 11 maternal mutations
      and 7 unclear of parental origin). The mutation in the paternal germline was 3.3
      times higher than in the maternal germline. The results of our study show, that
      apart from the vast majority of single-step mutations rare multi-step mutations
      can be observed. Therefore, the interpretation of mutational events should not
      rigidly be restricted to the shortest possible mutational step, because rare but
      true multi-step mutations can easily be overlooked, if haplotype analysis is not
      possible.

PMID- 21873137
TI  - Fourteen short tandem repeat loci Y chromosome haplotypes: Genetic analysis in
      populations from northern Brazil.
AB  - Fourteen Y-STR loci (DYS458, DYS439, Y-GATA H4, DYS576, DYS447, DYS460, DYS456,
      YGATA A10, DYS437, DYS449, DYS570, DYS635 or Y-GATA C4, DYS448 and DYS438) were
      analysed in 873 males from eight northern Brazil populations: Belem (N=400),
      Santarem (N=69), Manaus (N=75), Macapa (N=65), Palmas (N=30), Rio Branco (N=32),
      Porto Velho (N=135) and Boa Vista (N=67). A total of 871 different haplotypes
      were identified, of which 869 were unique. The panel's estimated total haplotype
      diversity (HD) is 0.9988, and its discrimination capacity (DC) is 0.9980. The
      lowest estimates of genetic diversity correspond to markers Y-GATA H4 (0.550) and
      DYS460 (0.581), and the greatest (above 0.700) to markers DYS458, DYS576, DYS447,
      YS449, DYS570 and DYS635. The genetic parameters obtained were higher for the 14
      Y-STR panel than that for the minimum haplotype set (HD=0.9969; DC=0.76) and the
      parameters were similar to those obtained with the panel of 17 YSTR of YHRD
      (HD=0.9987; DC=0. 9870). The analysis of molecular variance (AMOVA) indicated
      that most of the genetic variance is found within populations and a smaller, but
      significant part, is found among populations (R(ST)=0.027, p value=0.009). The
      data when compared with those from African, Amerindian and European populations
      have shown no significant genetic distance between northern Brazil populations
      and Europeans, but there is a significant genetic distance when compared to
      Africans and Amerindians. The discrimination capacity of the markers shows a high
      potential for forensic analysis.

PMID- 21873138
TI  - Distal osteotomy of the lateral metatarsals: a series of 72 cases comparing the
      Weil osteotomy and the DMMO percutaneous osteotomy.
AB  - INTRODUCTION: A Weil osteotomy with internal fixation can match the preoperative
      plan by precisely setting the metatarsal length; however 10 to 30% of patients
      end up experiencing postoperative stiffness. A percutaneous distal metatarsal
      mini-invasive osteotomy (DMMO) is a purely extra-articular technique; metatarsal
      length is set automatically upon weight bearing of the foot. The goal of this
      study was to compare these two osteotomy techniques when performed on the three
      or four most lateral metatarsals. HYPOTHESIS: A DMMO will result in better joint
      motion than a Weil osteotomy. PATIENTS AND METHODS: This was a retrospective,
      single center, single surgeon study with 72 patients. Group 1 consisted of 39
      patients operated by the DMMO technique. Group 2 consisted of 33 patients
      operated by the standard Weil osteotomy technique. In some cases, a procedure on
      the first ray (Scarf or fusion) was also performed. The age, gender and
      procedures on the first ray were comparable for both groups. Patients were
      evaluated with clinical (AOFAS score) and radiological outcomes (Maestro
      criteria) at 3 and 12 months minimum follow-up. RESULTS: Sixty-seven patients
      were seen again with an average follow-up of 14.8 months (range 12-24). The
      postoperative AOFAS score was comparable in both groups (86.5 and 85.3,
      respectively). The joint range of motion was comparable in both groups. Static
      problems (oedema, metatarsalgia, hyperkeratosis and dislocation) were comparable
      at the last follow-up. The metatarsalgia recurred in four patients from group 1
      and five patients from group 2. After 3 months, oedema and metatarsalgia were
      significantly greater in group 1. Radiological measurements (M1P1angle, M1M2angle
      and Maestro criteria) were comparable. Metatarsal head recoil was identical
      between each ray in group 1. At the last follow-up, all the osteotomy sites had
      achieved union. DISCUSSION AND CONCLUSION: The results of static metatarsalgia
      treatment were comparable when using a DMMO or Weil osteotomy. However the DMMO
      had longer postoperative recovery, notably because of oedema. The percutaneous
      DMMO technique did not improve joint range of motion. LEVEL OF EVIDENCE: III,
      comparative retrospective study.

PMID- 21873139
TI  - Bone mineral density assessed by dual-energy X-ray absorptiometry in patients
      with viral or alcoholic compensated cirrhosis. A prospective study.
AB  - BACKGROUND/AIM: Cirrhosis is considered as a risk factor for osteoporosis whose
      prevalence is poorly known. The aim was to assess prospectively bone mineral
      density (BMD) in patients with alcoholic or viral compensated cirrhosis. METHODS:
      From 2006 to 2008, patients with viral or alcoholic compensated cirrhosis had BMD
      assessment by dual-energy X-ray absorptiometry. The prevalence of osteopenia (
      2.5SD <T-score<-1SD) and osteoporosis (T-score <=-2.5SD), and the influence of
      age, gender and aetiology of cirrhosis were assessed using univariate and
      multiple regression analysis. RESULTS: One hundred and nine patients were studied
      (72 men, 55.3 +/- 11.4 years and 37 women, 65.2 +/- 11.0); with HBV (n=35), HCV
      (n=43), or alcoholic cirrhosis (n=31). At the lumbar spine, 25 patients had
      osteopenia and 12 had osteoporosis. At the femoral site, 23 had osteopenia and 4
      had osteoporosis. Female gender had an independent decreased effect on the total
      BMD. CONCLUSIONS: The prevalence of osteoporosis was up to 11% at the lumbar
      spine, greater in women independently of age, without significant difference
      according to the aetiology of cirrhosis.

PMID- 21873140
TI  - Critical factors differentiating erythema multiforme majus from Stevens-Johnson
      syndrome (SJS)/toxic epidermal necrolysis (TEN).
AB  - Erythema multiforme majus (EMM) and Stevens-Johnson syndrome (SJS)/toxic
      epidermal necrolysis (TEN) are severe cutaneous reactions characterised by
      targetoid erythematous lesions and mucocutaneous involvement. The initial skin
      manifestations are similar, making early diagnosis difficult. We retrospectively
      reviewed 36 cases of EMM and 18 cases of SJS/TEN and also evaluated 6 patients
      with unclassified EMM. 13 patients in the EMM group and 16 patients in the
      SJS/TEN group presented with a high fever (>38.5C; p<0.001). Two or more mucous
      membranes were affected in 6 patients in the EMM group and 18 patients in the
      SJS/TEN group. Significantly more SJS/TEN than EMM patients had high levels of C
      reactive protein and severe hepatic dysfunction. Thirteen EMM and 13 SJS/TEN
      cases were caused by medications/drugs. Skin biopsy samples showed stronger
      mononuclear cell infiltration in the EMM than in the SJS/TEN group (p<0.001). The
      mean dose of initial systemic corticosteroid used to treat EMM was lower than
      that used to treat SJS/TEN. No patients died in either group. Clinically, the
      unclassified cases mostly behaved like EMM. The results of our investigation
      suggest that EMM and SJS/TEN are distinct conditions and they help in
      differentiating these syndromes at an early stage.

PMID- 21873141
TI  - Overexpression of autophagy-related beclin-1 in cutaneous squamous cell carcinoma
      with lymph-node metastasis.

PMID- 21873142
TI  - Perioral myoclonia with absences and myoclonic status aggravated by
      oxcarbazepine.
AB  - Perioral myoclonia with absences belongs to the "idiopathic generalised epilepsy
      syndromes in development", currently not yet cited in the ILAE classification.
      This epilepsy syndrome is associated with a seizure type that appears to be
      specific. Here, we report polygraphic recordings of this seizure type in a young
      boy, previously misdiagnosed with focal epilepsy. EEG and clinical features were
      useful to differentiate diagnosis of his seizures from other absence or myoclonic
      seizures. Interestingly, some seizures were associated with neck myoclonia. Home
      video recording of myoclonic status aggravated by inappropriate treatment is also
      presented. [Published with video sequences].

PMID- 21873143
TI  - Compression therapy: an adjuvant treatment for orofacial granulomatosis in
      Melkersson-Rosenthal syndrome?

PMID- 21873144
TI  - Generalized granuloma annulare following BCG vaccination, mimicking papular
      tuberculid.

PMID- 21873145
TI  - Bilaterally independent epileptic spasms in a case of Aicardi syndrome.
AB  - A girl with Aicardi syndrome was observed to have two distinct types of
      asymmetric epileptic spasms, as detected by ictal video-EEG recording at three
      months of age. When the two types of spasm concurred, they showed no mutual
      interactions based on either clinical or EEG aspects. This observation does not
      support the hypothesis that the brainstem always plays an initiating role in
      generating spasms. [Published with video sequences].

PMID- 21873146
TI  - [A simple method to determine and evaluate "effect size"].
AB  - Measurement of effect sizes is a practice that is increasingly encouraged, indeed
      required, by journals of psychological and social behaviour, in addition to the
      standard tests of statistical significance. This paper is a methodological note
      presenting the conceptual interest of the effect size, its main indicators and
      their interpretation.

PMID- 21873147
TI  - [Still disease in subSaharan Africa: report of four cases in Gabon].
AB  - Still disease is an inflammatory rheumatism occurring predominantly in children
      and adolescents, but which is sometimes diagnosed in adults. A combination of
      fever, arthralgia, transient dermatological lesions, hyperleucocytosis
      predominantly neutrophilic, and ferritinaemia greater than 1,000 MUg/L is
      suggestive of this disease, but infectious, haematological, immunological, and
      tumor diseases must first be ruled out. Accordingly, patients' financial
      limitations keep this disease from being diagnosed often in sub-Saharan Africa.
      We report four cases of Still disease with favourable outcome after
      corticosteroid therapy.

PMID- 21873148
TI  - [Sociocultural etiology to guide community control of malaria in Cote d'Ivoire].
AB  - In the rural communities of Cote d'Ivoire, malaria control is guided by the
      sociocultural etiology or perception of this disease, as we can see by studies
      conducted in the Baoule and Gouro communities. These studies show that these
      communities establish a link between the sun, excessive oil consumption,
      agricultural activities, disease, and lack of hygiene. Mosquitoes, however, are
      not identified as the cause of malaria but rather as an insect noxious by their
      noise and painful bites. These populations use both traditional and modern means
      to move mosquitoes away from their homes. Analysis of this social reality shows
      that the battle against malaria in rural areas is not simply a problem of health
      education. It is thus important in developing malaria control programmes to adopt
      a strategy that links community participation and health education.

PMID- 21873149
TI  - [HELLP syndrome: nine cases treated at Josephine-Bongo Maternity Hospital].
AB  - INTRODUCTION: the aim of this study was to evaluate the management of HELLP
      syndrome at Josephine-Bongo Maternity Hospital. STUDY POPULATION AND METHODS: the
      retrospective study included all women admitted to the intensive care unit of our
      hospital from 1 January 2004 through 30 December 2007 with HELLP syndrome. The
      characteristics studied included: age, parity, number of previous pregnancies,
      antenatal monitoring, term at onset, clinical and laboratory signs, treatment,
      complications, perinatal and neonatal mortality and duration of intensive care
      unit admission. RESULTS: nine patients, mainly primiparas with an average age of
      29.7 +/- 6.5 years were admitted to intensive care. HELLP syndrome was diagnosed
      at a mean term of 33 +/- 2.7 weeks. The clinical signs noted included the
      following: jaundice (100%), headaches (100%) and epigastric pain (67%). The
      laboratory analysis showed: a mean haemoglobin level of 8.7 +/- 1.2 g/dL, an
      average platelet level of 70,900 +/- 27,052.9/mm(3), and mean transaminase levels
      of 120 +/- 60 UI/L for aspartate aminotransferase (AST) and 99 +/- 41.1 UI/L for
      alanine aminotransferase (ALT). Hypertension was treated by continuous
      intravenous administration of nicardipine. The fetal pulmonary development was
      ensured with betamethasone. Delivery was by caesarean for four women (44%) and
      vaginal for the other five (56%). One maternal death was noted, related to a
      rupture of a subcapsular haematoma of liver. CONCLUSION: in view of the extent of
      perinatal morbidity and mortality associated with HELLP syndrome, abdominal
      ultrasonography to detect any subcapsular haematoma of liver should be performed
      to determine the need for immediate delivery. It would be appropriate to provide
      the Josephine-Bongo Maternity Hospital with a neonatal intensive care unit of
      high quality.

PMID- 21873150
TI  - Using the internet to understand smokers' treatment preferences: informing
      strategies to increase demand.
AB  - BACKGROUND: Most smokers attempt to quit on their own even though cessation aids
      can substantially increase their chances of success. Millions of smokers seek
      cessation advice on the Internet, so using it to promote cessation products and
      services is one strategy for increasing demand for treatments. Little is known,
      however, about what cessation aids these smokers would find most appealing or
      what predicts their preferences (eg, age, level of dependence, or timing of quit
      date). OBJECTIVE: The objective of our study was to gain insight into how
      Internet seekers of cessation information make judgments about their preferences
      for treatments, and to identify sociodemographic and other predictors of
      preferences. METHODS: An online survey assessing interest in 9 evidence-based
      cessation products and services was voluntarily completed by 1196 smokers who
      visited the American Cancer Society's Great American Smokeout (GASO) webpage.
      Cluster analysis was conducted on ratings of interest. RESULTS: In total, 48%
      (572/1196) of respondents were "quite a bit" or "very much" interested in
      nicotine replacement therapy (NRT), 45% (534/1196) in a website that provides
      customized quitting advice, and 37% (447/1196) in prescription medications. Only
      11.5% (138/1196) indicated similar interest in quitlines, and 17% (208/1196) in
      receiving customized text messages. Hierarchical agglomerative cluster analysis
      revealed that interest in treatments formed 3 clusters: interpersonal-supportive
      methods (eg, telephone counseling, Web-based peer support, and in-person group
      programs), nonsocial-informational methods (eg, Internet programs, tailored
      emails, and informational booklets), and pharmacotherapy (NRT, bupropion, and
      varenicline). Only 5% (60/1196) of smokers were "quite a bit" or "very much"
      interested in interpersonal-supportive methods compared with 25% (298/1196) for
      nonsocial-informational methods and 33% (399/1196) for pharmacotherapy.
      Multivariate analyses and follow-up comparisons indicated that level of interest
      in pharmacotherapy ("quite a bit or "very much" vs. "not at all") varied as a
      function of education (n = 575, chi(2) (3) =16.6, P = .001), age (n = 528, chi(2)
      (3) = 8.2, P = .04), smoking level (n = 514, chi(2) (3) = 9.5, P = .02), and when
      smokers were planning to quit (n = 607, chi(2) (4) = 34.0, P < .001).
      Surprisingly, greater age was associated with stronger interest in nonsocial
      informational methods (n = 367, chi(2) (3) = 10.8, P = .01). Interest in
      interpersonal-supportive methods was greater if smokers had used a quitline
      before (n = 259, chi(2) (1) = 18.3, P < .001), or were planning to quit earlier
      rather than later (n = 148, chi(2) (1) = 4.9, P = .03). CONCLUSIONS: Smokers
      accessing the Internet for information on quitting appear to differentiate
      cessation treatments by how much interpersonal interaction or support the
      treatment entails. Quitting date, smoking level, and sociodemographic variables
      can identify smokers with varying levels of interest in the 3 classes of
      cessation methods identified. These results can potentially be used to more
      effectively target and increase demand for these treatments among smokers
      searching the Internet for cessation information.

PMID- 21873152
TI  - KRAS-induced actin-interacting protein: a potent target for obesity, diabetes and
      cancer.
AB  - KRAS-induced actin-interacting protein (KRAP) was originally identified as one of
      the genes deregulated in colorectal cancer. KRAP encodes a cytoplasmic protein
      associated with filamentous-actin (F-actin), and the amino acid sequences are
      highly conserved among KRAP orthologues from fish to mammalian species. We
      demonstrated that KRAP-deficient mice show altered whole-body energy metabolism
      and resistance to diet-induced obesity and diabetes. Although the precise
      mechanisms underlying the metabolic phenotypes in the KRAP-deficient mice remain
      unclear, KRAP is considered to be a target for metabolism-related diseases.
      Furthermore, several groups have reported that KRAP is a cancer-associated gene.
      Further studies on the molecular functions of KRAP in physiological tissues could
      provide a better understanding of various diseases, and opportunities for
      intervention in various human diseases. In this review, we summarize the current
      understanding of KRAP and the roles that it plays in a variety of diseases.

PMID- 21873153
TI  - Induction of cytotoxic T lymphocytes by CEA peptide-pulsed gammadelta T-cells
      isolated from patients with advanced cancer.
AB  - Cytotoxic gammadelta T-cells recognize antigens directly without the need for
      antigen processing and presentation. Recently, it was reported that they can also
      present antigens and proliferate in vitro. In this study, we examined whether
      gammadelta T-cells isolated from patients with advanced cancer can be used for
      immunotherapy. Twenty-two inoperable patients with multiple cancer metastases
      were enrolled in the study. There was no significant difference in the ratio of
      gammadelta T-cells within the peripheral blood mononuclear cell population
      isolated from healthy volunteers and cancer patients. gammadelta T-Cells isolated
      from cancer patients were expanded 2- to 5-fold using zoledronic acid or 2-methyl
      3butenyl-1-pyrophosphate and IL-2. Autologous CD8(+) T-cells co-cultured with
      expanded CEA peptide-pulsed gammadelta T-cells from cancer patients with HLA-A24
      killed more CEA-positive HLA-A24-matched gastric cancer cells and secreted higher
      levels of interferon-gamma. These results suggest that gammadelta T-cells from
      cancer patients may be ideal candidates for adoptive immunotherapy.

PMID- 21873154
TI  - Sonodynamic cancer therapy: a non-invasive and repeatable approach using low
      intensity ultrasound with a sonosensitizer.
AB  - The low-intensity ultrasound that is used in clinical diagnoses, such as abdomen
      echo inspection, is a non-invasive treatment, and penetrates deeper into the body
      than light. Recently, sonodynamic therapy (SDT), which uses low-intensity
      ultrasound together with a sonosensitizer, has been developed for cancer therapy
      in applying such properties of ultrasound. So far, most sonosensitizers that have
      been developed are sensitive to light as well as ultrasound, implying that the
      shortcomings of photosensitizers used during photodynamic therapy, such as skin
      sensitivity, still need to be overcome in SDT. Some exceptions were, however,
      reported in recent studies in which sensitizers were activated mainly by
      ultrasound but not by light. Furthermore, recent in vivo studies have
      demonstrated that SDT with a sonosensitizer has a great potential as a non
      invasive and repeatable treatment for cancer therapy.

PMID- 21873155
TI  - Oral administration of lipopolysaccharides for the prevention of various
      diseases: benefit and usefulness.
AB  - It is well known that intravenous administration of lipopolysaccharide (LPS)
      induces severe toxicity in mammals. The maximum tolerated dose of intravenous
      administration of LPS in humans is reported to be only 1 to 4 ng/kg body weight.
      However, oral administration of a high dose of LPS caused no toxicity or systemic
      inflammation in other mammals, birds, or fish. Two weeks of oral administration
      of a high dose of LPS (2 mg/kg) did not induce toxicity in a rat experiment.
      Moreover, several experiments have reported that oral administration of LPS had
      preventative and curative properties against various diseases, including
      allergic, and lifestyle-related diseases. These results demonstrate that mucosal
      administration of LPS acts via a different regulatory mechanism in biological
      responses from that of parenteral administration. Mucosal administration of LPS
      is thought to be quite promising for prevention of diseases, but LPS is rarely
      used. In order to expand the usage of oral administration of LPS for preventing
      lifestyle and allergic diseases, it will be necessary to clarify the mechanisms
      that arouse immune responses after oral administration of LPS. This short review
      presents a recent observation of the usefulness of orally administered LPS.

PMID- 21873156
TI  - Lipopolysaccharide IP-PA1 from Pantoea agglomerans prevents suppression of
      macrophage function in stress-induced diseases.
AB  - Chronic psychological stress impairs health and induces various diseases by
      causing an imbalance in the immune, neuropsychiatric and endocrine systems. The
      primary reason for the development of stress-induced disease is suppression of
      macrophage function, which plays a pivotal role in innate immunity. In fact,
      surgical stress has been shown to exacerbate opportunistic infections by
      significantly suppressing macrophage function. Conversely, administration of
      macrophage activating substances before surgery, such as tumor necrosis factor
      (TNF)-alpha or Picibanil (OK-432), has been shown to protect against macrophage
      suppression and the resulting exacerbation of infectious diseases, and against
      tumor metastasis in the lungs. Thus, if suppression of macrophage function by
      stress could be safely prevented by use of a macrophage activating substance, the
      detrimental side effects of stress could be reduced. Recently, we identified a
      lipopolysaccharide, IP-PA1, derived from Pantoea agglomerans, a symbiotic Gram
      negative bacteria found in wheat and other food plants. Oral administration of IP
      PA1 demonstrated macrophage activation (priming) and protective effects against
      infection, allergy and cancer, without any side-effects. In this review, the
      possibility of using IP-PA1 as a safe, macrophage activating substance for
      prevention of stress-induced impairments is discussed.

PMID- 21873157
TI  - WT1 peptide vaccine stabilized intractable ovarian cancer patient for one year: a
      case report.
AB  - We report on Wilms tumor (WT1) peptide immunotherapy in a patient with
      intractable ovarian cancer patient over an extended period. CASE REPORT:
      Immunotherapy using WT1 peptide has been undergoing clinical trials for
      gynecological cancer. We used WT1 peptide vaccination to treat a 53-year-old
      woman suffering from ovarian cancer with peritoneal dissemination. After 2
      months, her pleural and cardiac effusion had disappeared, and the sum of the
      longest diameter of the target lesion (in the pelvic mass) was reduced. There was
      a weak positive correlation between CA125 and mononuclear phagocyte/lymphocyte
      ratio (Spearman's rho=0.275, p=0.015). Intradermally administered WT1 peptide
      vaccination in a case of intractable ovarian cancer stabilized the disease over
      the course of one year. However, the immunotherapeutic mechanism of WT1 peptide
      and immunological escape mechanism for carcinoma cells remain to be elucidated.

PMID- 21873158
TI  - Frequency of myeloid dendritic cells can predict the efficacy of Wilms' tumor 1
      peptide vaccination.
AB  - BACKGROUND: The object of this study was to investigate the clinical predictive
      capability of peripheral myeloid dendritic cells (DCs) in Wilms' tumor 1 (WT1)
      vaccine therapy for patients with gynaecological cancer. PATIENTS AND METHODS:
      Six patients with WT1/human leukocyte antigen (HLA)-A*2402-positive
      gynaecological cancer were included in this study. The patients received
      intradermal injections of a modified 9-mer WT1 peptide every week for 12 weeks.
      Peripheral blood samples were obtained at 0, 4, 8 and 12 weeks after the initial
      vaccination. Circulating DCs were detected by flow cytometry. RESULTS: The
      frequencies of CD14(+)CD16(+)CD33(+)CD85(+) myeloid DCs were significantly higher
      in the therapeutically effective group than in therapeutically inert group
      (p<0.05). CONCLUSION: These results suggested that myeloid DCs, which should be
      associated with inducing cytotoxic T-cells, provided additional prognostic
      information in the use of cancer peptide vaccine.

PMID- 21873159
TI  - Oncogenic KRAS regulates miR-200c and miR-221/222 in a 3D-specific manner in
      colorectal cancer cells.
AB  - BACKGROUND: Oncogenic KRAS plays several key roles in a three-dimensional (3D)
      colonic-crypt model. However, miRNA expression regulated by oncogenic KRAS in
      this model is still elusive. MATERIALS AND METHODS: The differential expression
      of 105 cancer-related microRNAs was examined and compared in HCT116 cells and
      HKe3 cells (HCT116 cells in which mutated KRAS allele was deleted) in 3D culture.
      HKe3 cells stably overexpressing oncogenic KRAS and the public datasets for
      microRNA expression analysis of colorectal cancer were further examined. RESULTS:
      The increased expression of miR-200c, miR-221 and miR-222 were observed
      exclusively in 3D culture, but not in the two-dimensional culture. These
      microRNAs were regulated by oncogenic KRAS and were significantly overexpressed
      in human colorectal tumor specimens. Of note, the protein expression level of
      Phosphatase and tensin homolog (PTEN), a putative target of miR-221/222 cluster,
      was reduced under the control of oncogenic KRAS in a 3D-specific manner.
      CONCLUSION: Oncogenic KRAS regulates 3D-specific molecules, possibly being
      associated with colorectal tumor development in vivo.

PMID- 21873161
TI  - Functional characterization of lipopolysaccharide derived from symbiotic bacteria
      in rice as a macrophage-activating substance.
AB  - BACKGROUND AND AIM: Lipopolysaccharide derived from a symbiotic bacterium in
      wheat (Pantoea agglomerans, LPSp) has shown multiple positive effects, such as
      prophylactic, antiallergic and antitumour effects, without serious side-effects.
      LPSp has differential biological activities in comparison to other LPS, such as
      those from Escherichia coli (LPSe). The only difference between LPSp and LPSe is
      in the O-antigen polysaccharide structure (O-PS). This led us to the hypothesis
      that the O-PS structure would seem to participate in biological activities. Thus,
      the characterization of properties of O-PS in LPS is of the utmost importance for
      understanding cell activation in the maintenance of homeostasis. However, little
      is known about the correlation between the O-PS structure of LPS and its
      biological activities. In this study, we extracted LPS derived from a symbiotic
      bacterium in rice (strain A46, related species of Pantoea), which has a long
      history of use in foods, and investigated its putative structures and functions.
      MATERIALS AND METHODS: LPS derived from strain A46 was prepared using a hot
      phenol extraction method. The properties of LPS-A46 were analysed by thin-layer
      chromatography, Tricine SDS-PAGE and Western blotting. The function of LPS-A46
      was analyzed by quantative real-time PCR and flow cytometry using THP-1 cells and
      Peripheral blood mononuclear cell (PBMC) derived macrophages. RESULTS: In Tricine
      SDS-PAGE, high molecular mass LPS-A46 had a molecular mass lower than that of
      LPSp. In Western blotting, LPS-A46 reacted with lipid A antibody but did not
      react with an O-PS antibody of LPSp. In comparison to other LPS, LPS-A46 induced
      a differential cytokine gene expression profile in THP-1 cells and PBMC-derived
      macrophages. CONCLUSION: The present study suggests that LPS derived from
      symbiotic bacterium in rice is a bioactive functional LPS which may have
      different functional activities compared to other types of LPS.

PMID- 21873160
TI  - A possible clinical adaptation of CRM197 in combination with conventional
      chemotherapeutic agents for ovarian cancer.
AB  - AIM: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a
      promising target for cancer therapy. We have already started a phase I study of
      CRM197, a specific HB-EGF inhibitor, for advanced ovarian cancer. In this study,
      we evaluated possible clinical adaptations of CRM197 in combination with
      conventional chemotherapeutic agents. MATERIALS AND METHODS: CRM197, bevacizumab,
      and paclitaxel were intraperitoneally administered either alone or in combination
      with mice xenografted with ES2 human ovarian cancer cells. The tumor volumes and
      microvessel densities (MVD) were determined. RESULTS: Enhanced antitumor effects
      were observed when paclitaxel was used in combination with bevacizumab or CRM197.
      The antitumor effect of paclitaxel/CRM197 was significantly higher than that of
      paclitaxel/bevacizumab. The tumor MVD of mice treated with paclitaxel/CRM197 was
      significantly lower than that of mice treated with paclitaxel/bevacizumab.
      CONCLUSION: CRM197 in combination with paclitaxel significantly blocked tumor
      formation and angiogenesis. These results suggest that paclitaxel is a suitable
      candidate for CRM197 combination therapy.

PMID- 21873162
TI  - Design, synthesis and destructive dynamic effects of BODIPY-containing and
      curcuminoid boron tracedrugs for neutron dynamic therapy.
AB  - BACKGROUND: We previously designed the boron tracedrugs UTX-42, UTX-43, and UTX
      44, which possess antioxidant potency. In order to explore their destructive
      dynamic effects when bombarded by weak thermal neutrons, we performed thermal
      neutron irradiation of bovine serum albumin (BSA) treated with the boron
      tracedrugs. MATERIALS AND METHODS: Boron tracedrugs, including the boron
      dipyrromethene (BODIPY)-containing compounds UTX-42, UTX-44, and UTX-47 and the
      curcuminoid compounds UTX-50 and UTX-51, were designed for neutron dynamic
      therapy based on their molecular orbital calculation. Newly designed UTX-47, UTX
      50, and UTX-51 were synthesized. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was performed to detect decomposition by thermal
      neutron irradiation of BSA treated with these boron tracedrugs. RESULTS: The
      combination of 1.0 MUM BSA with 100 MUM of each of the boron tracedrugs showed a
      decrease in band intensity after irradiation. CONCLUSION: All boron tracedrugs
      tested caused destructive dynamic damage of BSA during thermal neutron
      irradiation, suggesting that boron tracedrugs could be used as dynamic drugs for
      neutron dynamic therapy.

PMID- 21873163
TI  - Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute
      lymphoblastic leukemia.
AB  - The therapeutic outcome for T-cell acute lymphoblastic leukemia (T-ALL) remains
      poor; thus, novel, targeted therapies are urgently needed. Recently, we showed
      that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a
      member of the EGF family, is a promising target for the treatment of various
      types of cancer. The aim of the present study was to investigate whether HB-EGF
      is a therapeutic target for T-ALL, and to further elucidate the antitumor effects
      of a specific inhibitor of HB-EGF, cross-reacting material 197 (CRM197). We
      elucidated the expression of HB-EGF in T-ALL cell lines, and evaluated the effect
      of CRM197 on these cells alone or in combination with anticancer agent. The
      expression of EGFR and EGFR ligands was determined by flow cytometry, RT-PCR and
      real-time quantitative PCR. Induction of apoptosis was assessed by TUNEL assay.
      HB-EGF was strongly expressed by T-ALL cell lines, and the expression of both HB
      EGF and EGFR was enhanced by doxorubicin. CRM197 induced apoptosis, and
      furthermore, the combination of CRM197 plus doxorubicin enhanced cytotoxicity in
      a T-ALL cell line. These results suggest that HB-EGF is a promising therapeutic
      target for T-ALL.

PMID- 21873164
TI  - Effect of the Gc-derived macrophage-activating factor precursor (preGcMAF) on
      phagocytic activation of mouse peritoneal macrophages.
AB  - BACKGROUND: The 1f1f subtype of the Gc protein (Gc(1f1f) protein) was converted
      into Gc-derived macrophage-activating factor (GcMAF) by enzymatic processing in
      the presence of beta-galactosidase of an activated B-cell and sialidase of a T
      cell. We hypothesized that preGc(1f1f)MAF, the only Gc(1f1f) protein lacking
      galactose, can be converted to GcMAF in vivo because sialic acid is cleaved by
      residual sialidase. Hence, we investigated the effect of preGc(1f1f)MAF on the
      phagocytic activation of mouse peritoneal macrophages. RESULTS: We examined the
      sugar moiety of preGc(1f1f)MAF with a Western blot using peanut agglutinin (PNA)
      and Helix pomatia agglutinin (HPA) lectin. We also found that preGc(1f1f)MAF
      significantly enhanced phagocytic activity in mouse peritoneal macrophages but
      only in the presence of the mouse peritoneal fluid; the level of phagocytic
      activity was the same as that observed for GcMAF. CONCLUSION: PreGc(1f1f)MAF can
      be used as an effective macrophage activator in vivo.

PMID- 21873165
TI  - Differential expression of mRNA in human monocytes following interaction with
      human colon cancer cells.
AB  - Monocytes are known to differentiate into tissue-specific macrophages in response
      to the tissue environment, and it has been suggested that tumor-associated
      macrophages might promote angiogenesis. Therefore, the factors associated with
      monocyte differentiation into tumor-associated macrophages may become new targets
      for cancer therapy. However, these factors remain unclear in human colon cancer.
      The aim of this study was to identify the factors associated with human monocyte
      differentiation into tumor-associated macrophages at human colon cancer sites.
      MATERIALS AND METHODS: A human monocyte cell line (THP-1) was co-cultured with a
      human colon cancer cell line (DLD-1) and mRNA expression was analyzed by
      quantitative real-time PCR. RESULTS: In THP-1 cells, monocyte chemotactic protein
      (MCP)-1 mRNA expression increased in a time-dependent manner from day 3 after co
      culture with DLD-1 cells; furthermore, expression of vascular endothelial growth
      factor (VEGF)-A, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and
      IL-8 mRNA was increased from day 5. This increase in mRNA expression in the THP-1
      cells was attributable to the presence of the DLD-1 cells. Therefore, MCP-1, VEGF
      A, TNF-alpha, IL-1beta, and IL-8 are suggested to be associated with
      differentiation of human monocytes into tumor-associated macrophages at human
      colon cancer sites.

PMID- 21873166
TI  - Clinical course of colorectal cancer in patients with ulcerative colitis.
AB  - BACKGROUND: Colorectal cancer that develops as a complication of ulcerative
      colitis (UC) is a serious problem that affects the patient's prognosis. Such
      cancer is characterized by development at an early age, a high incidence of
      multiple tumors, poorly differentiated carcinoma and mucinous carcinoma. Special
      attention should therefore be paid to the diagnosis and treatment of such cancer.
      PATIENTS AND METHODS: One hundred and seventy-four patients with UC underwent
      surgery in our Department between July of 1985 and December of 2009. Of these, 22
      had concomitant colorectal cancer. We performed a retrospective study to
      investigate these patients. RESULT: The incidence of colorectal cancer as a
      complication of UC was 12.6%. The male:female ratio was 14:8, and the average age
      at surgery was 54.6 (32-79) years. In addition, when examining the lesion type of
      UC, it was revealed that the total colitis type accounted for 77.3% of colorectal
      cancer cases in UC patients. Regarding the site of development of colorectal
      cancer, 14 out of the 22 patients had cancer in the distal end. The average
      period from the development of UC to the diagnosis of colorectal cancer was 14.7
      (0.6-40.5) years. The cumulative incidence rates over 10 and 20 years were 5.1%
      and 17.5%, respectively. Histologically, poorly differentiated adenocarcinoma and
      mucinous carcinoma were confirmed in 38.1% of the patients, and dysplasia was
      also confirmed in 53.8%. In addition, multiple tumors were confirmed at a rate as
      high as 27.3%. Cancer detection through surveillance has increased, and
      colorectal cancer was detected in 13 out of the 22 patients by routine
      surveillance. In cases where cancer was detected by surveillance colonoscopy,
      46.2% of lesions were early cancer. We therefore consider that surveillance is
      useful. However, we experienced a case that could not be diagnosed by endoscopy
      that was successfully diagnosed by fluoroscopy. The case was noted to have
      stricture. CONCLUSION: The cumulative incidence rates over 10 and 20 years were
      5.1% and 17.5%, respectively. Since the average period from the onset of UC to
      the diagnosis of colorectal cancer was 14.7 years, routine surveillance
      examinations are necessary for patients with a history of UC of at least 10
      years. In addition, patients with strictures must be examined using both
      colonoscopy and fluoroscopy because diagnosis with colonoscopy alone may be
      inadequate.

PMID- 21873167
TI  - Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in
      hepatocellular carcinoma via the NKG2D-MICA/B system.
AB  - AIM: Natural-killer group 2, member D (NKG2D) is an activating receptor on
      natural killer cells and activated T-cells, designated cytokine-activated killer
      (CAK) cells here. The MHC class I chain-related A and B (MICA and MICB,
      respectively) are ligands of NKG2D and are expressed on various human tumor
      cells, including hepatocellular carcinoma (HCC) cells. Here, we investigate
      whether gemcitabine, a chemotherapeutic agent, affects MICA/B expression in HCC.
      MATERIALS AND METHODS: We used ELISA, RT-PCR and adherent target detachment
      assays to determine expression of MICA/B in HepG2 HCC cells and the level of
      cellular cytotoxicity generated by treatment with gemcitabine and/or CAK cells.
      RESULTS: Surface expression of MICA/B was evident after gemcitabine treatment,
      and MICB-specific mRNA was up-regulated. Pre-treatment with gemcitabine and
      subsequent exposure to CAK cells induced greater cytotoxicity than either
      treatment alone. Inclusion of soluble MICB significantly reduced cytotoxicity.
      CONCLUSION: Gemcitabine induced MICA/B expression in HepG2 cells, resulting in
      synergistic enhancement of the cytotoxic effects of NKG2D-high CAK cells. The
      combination of gemcitabine and CAK cells may have clinical therapeutic
      significance for HCC.

PMID- 21873168
TI  - Novel complementary peptides to target molecules.
AB  - We generated an evolutionary computer program that generates complementary
      peptide (C-pep) sequences, with the potential to interact with a target peptide,
      by comparing several physico-chemical parameters of each pair of the
      complementary peptides being analyzed. We generated C-peps to target several
      molecules. About 30% of synthesized C-peps interfered with the function of their
      targets. C5a stimulates generation of TNFalpha and other inflammatory cytokines.
      Inhibition of C5a should be effective against sepsis, which impairs the status of
      cancer-bearing patients. One of the inhibitory C-peps of C5a, termed AcPepA, was
      effective in Cynomolgus monkeys intravenously infused with a lethal dose of
      bacterial LPS (4 mg/kg) destined to die. The monkeys were rescued by intravenous
      administration of 2 mg/kg/h of AcPepA. The excellent therapeutic effect of AcPepA
      is likely to be due to restriction of high mobility group box 1 (HMGB1) surge
      induced by the effect of C5a on C5L2, which is the second C5a receptor, since the
      released HMGB1 has the capacity to stimulate TLR4 as an endogeneous ligand
      resulting in further activation of inflammatory cells to release inflammatory
      cytokines forming a positive feedback circuit of inflammation.

PMID- 21873169
TI  - Decreased expression of claudin-1 in rectal cancer: a factor for recurrence and
      poor prognosis.
AB  - AIM: To investigate the potential involvement of claudin-1 (CL-1) in the
      tumorigenesis of rectal cancer by analyzing the correlation between CL-1
      expression, clinicopathological factors and prognosis. PATIENTS AND METHODS:
      Rectal cancer tissue specimens from 306 patients that had undergone surgical
      treatment were evaluated using immunohistochemical analysis for expression of CL
      1 and correlated with clinicopathological factors. RESULTS: A reduced expression
      of CL-1 (less than 30% of tumor cells strongly, positively stained) correlated
      significantly with poor prognosis in stage II and III rectal cancer. Moreover,
      the expression levels of CL-1 correlated significantly with tumor differentiation
      and perineural invasion (p=0.037 and 0.009, respectively). However, no
      significant differences were detected between the expression levels of CL-1 and
      other clinicopathological factors. CONCLUSION: Loss of claudin-1 expression is a
      strong predictor of disease recurrence and poor patient survival in stage II and
      III rectal cancer.

PMID- 21873170
TI  - Sonodynamic therapy with 5-aminolevulinic acid and focused ultrasound for deep
      seated intracranial glioma in rat.
AB  - BACKGROUND: 5-Aminolevulinic acid (5-ALA) has already been applied clinically as
      a photosensitizer. In this study, sonodynamically induced selective antitumour
      effect of 5-ALA for deep-seated lesions was evaluated. MATERIALS AND METHODS:
      First, normal rat brains were sonicated via a transducer placed on the dural
      surface to confirm safe acoustic conditions for normal rat brains. One week after
      inoculation of brains with C6 rat glioma cells, brains with/without
      administration of 5-ALA (100 mg/kg body weight) were sonicated. RESULTS:
      Sonodynamic therapy (SDT) with 5-ALA and focused ultrasound (10 W/cm(2), 1.04
      MHz, 5 min) achieved selective antitumour effect against deep-seated experimental
      glioma. Mean tumour sizes in the largest coronal section in sham-operated rats
      and rats receiving ultrasound with/without 5-ALA were 29.94+/-10.39, 18.32+/-5.69
      and 30.81+/-9.65 mm(2), respectively. Tumour size was significantly smaller in
      the SDT group than in other groups (p<0.05). CONCLUSION: This experimental rat
      model showed that SDT appears to be useful in the treatment of deep-seated
      malignant glioma.

PMID- 21873171
TI  - KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation
      of colorectal cancer cell lines.
AB  - BACKGROUND: We previously investigated the mRNA expression of colorectal cancer
      cell lines via a microarray analysis and found several genes that were
      significantly up-regulated by oncogenic KRAS under serum-starved conditions. Of
      these genes, we focused on ribonucleotide reductase M2 (RRM2), which was reported
      to be associated with DNA synthesis. MATERIALS AND METHODS: Cell proliferation
      and colony formation assays were performed using HCT116 cells transfected with
      lentiviral RRM2-shRNAs. RESULTS: Under serum-starved conditions, the expression
      level of RRM2 protein increased in HCT116 cells compared to HKe3 cells (HCT116
      cells with a disruption in oncogenic KRAS), and the re-expression of KRAS in HKe3
      cells induced the expression of RRM2. Both the cell proliferation under serum
      depleted conditions and the anchorage-independent growth were impaired by the
      reduction of RRM2 protein expression. CONCLUSION: RRM2 represents a novel
      therapeutic target, thus highlighting the potential utility of RRM2 inhibitors in
      colorectal cancer with oncogenic KRAS.

PMID- 21873172
TI  - Expression of IGF-1 and IGF-1R and their relation to clinicopathological factors
      in colorectal cancer.
AB  - BACKGROUND: Expression of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor
      (IGF-1R) has been shown to increase in colorectal cancer. We examined the
      correlation between expression of IGF-1 and IGF-1R and clinicopathological
      factors in colorectal cancer. PATIENTS AND METHODS: A prospective study was
      conducted of 210 colorectal cancer patients that underwent resection from January
      2002 to December 2004. The clinicopathological data was correlated to expression
      of IGF-1 and IGF-1R obtained from immunohistochemical analysis. Statistical
      analysis was carried using univariate and multivariate analysis. RESULTS: IGF1
      and IGF-1R staining was positive in 169 (80%) and 139 (66%) cases, respectively.
      Univariate and multivariate analyses showed significant correlation between
      expression of IGF-1 and tumor size (p=0.0024), and depth of invasion (p=0.0147).
      While IGF-1R was significantly correlated to tumor size and depth of invasion in
      univariate analysis, only tumor size (p=0.0658) had a strong association in
      multivariate analysis. CONCLUSION: Expression of IGF-1 and IGF-1R seems to
      increase with tumor size in colorectal cancer.

PMID- 21873173
TI  - Relationship between ulcerative colitis patients treated with leukocytapheresis
      and ulcerative colitis-associated colorectal cancer.
AB  - BACKGROUND: Leukocytapheresis (LCAP) is a recent modality for treatment of
      patients with ulcerative colitis (UC). This study aimed to assess whether LCAP
      changed the development of colorectal cancer (CRC) in patients with UC. PATIENTS
      AND METHODS: A total of 42 patients with UC underwent surgical treatment from
      January 2001 until October 2010 at Kurume University Hospital. The patient
      details, preoperative therapy, operative indication and complications were
      obtained from our prospective database. Univariate, multivariate analysis and
      tree model were used for statistical analysis. RESULTS: In patients who received
      LCAP before surgery, CRC was significantly less frequent (p=0.0321). CRC
      incidence following LCAP increased when the disease period from diagnosis of UC
      exceeded 133 months. Multivariate analysis showed that the odds for undergoing
      LCAP were significantly higher (p=0.0305) in those cases with a total dose of
      steroid more than 2.57 g. CONCLUSION: LCAP may suppress CRC in UC patients.

PMID- 21873174
TI  - Assessment of HB-EGF levels in peritoneal fluid and serum of ovarian cancer
      patients using ELISA.
AB  - BACKGROUND: Heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      is a rational target for ovarian cancer therapy. The aim of this study was to
      examine HB-EGF levels in the peritoneal fluid and serum of ovarian cancer (OVCA)
      patients. PATIENTS AND METHODS: Samples were collected from six healthy women, 21
      OVCA patients, and 21 ovarian cyst patients. HB-EGF levels were measured using a
      sandwich ELISA kit and calculated using a parallel line assay. RESULTS: No
      significant difference between the slopes of the standard and sample curves was
      observed at an anti-HB-EGF antibody concentration of 1.6 MUg/ml. HB-EGF levels in
      the peritoneal fluid and serum of OVCA patients were significantly higher than
      those in patients with ovarian cysts or controls. Serum HB-EGF levels were also
      significantly correlated with levels in peritoneal fluid in OVCA patients.
      CONCLUSION: We developed an assay for the exact measurement of HB-EGF levels in
      peritoneal fluid and serum.

PMID- 21873175
TI  - Efficiency of antimicrobial defense: molecular flexibility of natural defensin
      and artificial bis-quaternary ammonium compound.
AB  - BACKGROUND: Human alpha-defensins (such as HD5 and HD6) are typical bactericidal
      peptides. We examined the molecular features of HD5 and HD6 by molecular dynamics
      (MD) analysis. MATERIALS AND METHODS: Molecular features of natural defensins and
      artificial bis-quaternary ammonium compounds (e.g. 1,6-polymethylenedithio)bis(1
      octylpyridinium iodide: 4DTBP-m,8) were analyzed using molecular simulation
      techniques. RESULTS: HD5 and HD6 had different electrostatic potential profiles,
      which indicated the region-dependent hydrophobicity. 4DTBP-m,8 derivatives were
      significantly flexible, and many conformers existed. CONCLUSION: HD5 and HD6
      indicated antimicrobial activity by restricted conformation.

PMID- 21873176
TI  - On biodiversity conservation and poverty traps.
AB  - This paper introduces a special feature on biodiversity conservation and poverty
      traps. We define and explain the core concepts and then identify four distinct
      classes of mechanisms that define important interlinkages between biodiversity
      and poverty. The multiplicity of candidate mechanisms underscores a major
      challenge in designing policy appropriate across settings. This framework is then
      used to introduce the ensuing set of papers, which empirically explore these
      various mechanisms linking poverty traps and biodiversity conservation.

PMID- 21873177
TI  - Conditions associated with protected area success in conservation and poverty
      reduction.
AB  - Protected areas are the dominant approach to protecting biodiversity and the
      supply of ecosystem services. Because these protected areas are often placed in
      regions with widespread poverty and because they can limit agricultural
      development and exploitation of natural resources, concerns have been raised
      about their potential to create or reinforce poverty traps. Previous studies
      suggest that the protected area systems in Costa Rica and Thailand, on average,
      reduced deforestation and alleviated poverty. We examine these results in more
      detail by characterizing the heterogeneity of responses to protection conditional
      on observable characteristics. We find no evidence that protected areas trap
      historically poorer areas in poverty. In fact, we find that poorer areas at
      baseline seem to have the greatest levels of poverty reduction as a result of
      protection. However, we do find that the spatial characteristics associated with
      the most poverty alleviation are not necessarily the characteristics associated
      with the most avoided deforestation. We show how an understanding of these
      spatially heterogeneous responses to protection can be used to generate
      suitability maps that identify locations in which both environmental and poverty
      alleviation goals are most likely to be achieved.

PMID- 21873178
TI  - Lessons about parks and poverty from a decade of forest loss and economic growth
      around Kibale National Park, Uganda.
AB  - We use field data linked to satellite image analysis to examine the relationship
      between biodiversity loss, deforestation, and poverty around Kibale National Park
      (KNP) in western Uganda, 1996-2006. Over this decade, KNP generally maintained
      forest cover, tree species, and primate populations, whereas neighboring communal
      forest patches were reduced by half and showed substantial declines in tree
      species and primate populations. However, a bad decade for forest outside the
      park proved a prosperous one for most local residents. Panel data for 252
      households show substantial improvement in welfare indicators (e.g., safer water,
      more durable roof material), with the greatest increases found among those with
      highest initial assets. A combination of regression analysis and matching
      estimators shows that although the poor tend to be located on the park perimeter,
      proximity to the park has no measureable effect on growth of productive assets.
      The risk for land loss among the poor was inversely correlated with proximity to
      the park, initial farm size, and decline in adjacent communal forests. We
      conclude the current disproportionate presence of poor households at the edge of
      the park does not signal that the park is a poverty trap. Rather, Kibale appears
      to provide protection against desperation sales and farm loss among those most
      vulnerable.

PMID- 21873179
TI  - Land-use poverty traps identified in shifting cultivation systems shape long-term
      tropical forest cover.
AB  - In this article we illustrate how fine-grained longitudinal analyses of land
      holding and land use among forest peasant households in an Amazonian village can
      enrich our understanding of the poverty/land cover nexus. We examine the dynamic
      links in shifting cultivation systems among asset poverty, land use, and land
      cover in a community where poverty is persistent and primary forests have been
      replaced over time--with community enclosure--by secondary forests (i.e.,
      fallows), orchards, and crop land. Land cover change is assessed using aerial
      photographs/satellite imagery from 1965 to 2007. Household and plot level data
      are used to track land holding, portfolios, and use as well as land cover over
      the past 30 y, with particular attention to forest status (type and age). Our
      analyses find evidence for two important types of "land-use" poverty traps--a
      "subsistence crop" trap and a "short fallow" trap--and indicate that the initial
      conditions of land holding by forest peasants have long-term effects on future
      forest cover and household welfare. These findings suggest a new mechanism
      driving poverty traps: insufficient initial land holdings induce land use
      patterns that trap households in low agricultural productivity. Path dependency
      in the evolution of household land portfolios and land use strategies strongly
      influences not only the wellbeing of forest people but also the dynamics of
      tropical deforestation and secondary forest regrowth.

PMID- 21873180
TI  - Economic and geographic drivers of wildlife consumption in rural Africa.
AB  - The harvest of wildlife for human consumption is valued at several billion
      dollars annually and provides an essential source of meat for hundreds of
      millions of rural people living in poverty. This harvest is also considered among
      the greatest threats to biodiversity throughout Africa, Asia, and Latin America.
      Economic development is often proposed as an essential first step to win-win
      solutions for poverty alleviation and biodiversity conservation by breaking rural
      reliance on wildlife. However, increases in wealth may accelerate consumption and
      extend the scale and efficiency of wildlife harvest. Our ability to assess the
      likelihood of these two contrasting outcomes and to design approaches that
      simultaneously consider poverty and biodiversity loss is impeded by a weak
      understanding of the direction and shape of their interaction. Here, we present
      results of economic and wildlife use surveys conducted in 2,000 households from
      96 settlements in Ghana, Cameroon, Tanzania, and Madagascar. We examine the
      individual and interactive roles of wealth, relative food prices, market access,
      and opportunity costs of time spent hunting on household rates of wildlife
      consumption. Despite great differences in biogeographic, social, and economic
      aspects of our study sites, we found a consistent relationship between wealth and
      wildlife consumption. Wealthier households consume more bushmeat in settlements
      nearer urban areas, but the opposite pattern is observed in more isolated
      settlements. Wildlife hunting and consumption increase when alternative
      livelihoods collapse, but this safety net is an option only for those people
      living near harvestable wildlife.

PMID- 21873181
TI  - A review of financial instruments to pay for predator conservation and encourage
      human-carnivore coexistence.
AB  - One of the greatest challenges in biodiversity conservation today is how to
      facilitate protection of species that are highly valued at a global scale but
      have little or even negative value at a local scale. Imperiled species such as
      large predators can impose significant economic costs at a local level, often in
      poverty-stricken rural areas where households are least able to tolerate such
      costs, and impede efforts of local people, especially traditional pastoralists,
      to escape from poverty. Furthermore, the costs and benefits involved in predator
      conservation often include diverse dimensions, which are hard to quantify and
      nearly impossible to reconcile with one another. The best chance of effective
      conservation relies upon translating the global value of carnivores into tangible
      local benefits large enough to drive conservation "on the ground." Although human
      carnivore coexistence involves significant noneconomic values, providing
      financial incentives to those affected negatively by carnivore presence is a
      common strategy for encouraging such coexistence, and this can also have
      important benefits in terms of reducing poverty. Here, we provide a critical
      overview of such financial instruments, which we term "payments to encourage
      coexistence"; assess the pitfalls and potentials of these methods, particularly
      compensation and insurance, revenue-sharing, and conservation payments; and
      discuss how existing strategies of payment to encourage coexistence could be
      combined to facilitate carnivore conservation and alleviate local poverty.

PMID- 21873182
TI  - The effect of a protected area on the tradeoffs between short-run and long-run
      benefits from mangrove ecosystems.
AB  - Protected areas are used to sustain biodiversity and ecosystem services. However,
      protected areas can create tradeoffs spatially and temporally among ecosystem
      services, which can affect the welfare of dependent local communities. This study
      examines the effect of a protected area on the tradeoff between two extractive
      ecosystem services from mangrove forests: cutting mangroves (fuelwood) and
      harvesting the shrimp and fish that thrive if mangroves are not cut. We
      demonstrate the effect in the context of Saadani National Park (SANAPA) in
      Tanzania, where enforcement of prohibition of mangrove harvesting was
      strengthened to preserve biodiversity. Remote sensing data of mangrove cover over
      time are integrated with georeferenced household survey data in an econometric
      framework to identify the causal effect of mangrove protection on income
      components directly linked to mangrove ecosystem services. Our findings suggest
      that many households experienced an immediate loss in the consumption of mangrove
      firewood, with the loss most prevalent in richer households. However, all wealth
      classes appear to benefit from long-term sustainability gains in shrimping and
      fishing that result from mangrove protection. On average, we find that a 10%
      increase in the mangrove cover within SANAPA boundaries in a 5-km(2) radius of
      the subvillage increases shrimping income by approximately twofold. The creation
      of SANAPA shifted the future trajectory of the area from one in which mangroves
      were experiencing uncontrolled cutting to one in which mangrove conservation is
      providing gains in income for the local villages as a result of the preservation
      of nursery habitat and biodiversity.

PMID- 21873183
TI  - Index insurance for pro-poor conservation of hornbills in Thailand.
AB  - This study explores the potential of index insurance as a mechanism to finance
      community-based biodiversity conservation in areas where a strong correlation
      exists between natural disaster risk, keystone species populations, and the well
      being of the local population. We illustrate this potential using the case of
      hornbill conservation in the Budo-Sungai Padi rainforests of southern Thailand,
      using 16-y hornbill reproduction data and 5-y household expenditures data
      reflecting local economic well-being. We show that severe windstorms cause both
      lower household expenditures and critical nest tree losses that directly
      constrain nesting capacity and so reduce the number of hornbill chicks recruited
      in the following breeding season. Forest residents' coping strategies further
      disturb hornbills and their forest habitats, compounding windstorms' adverse
      effects on hornbills' recruitment in the following year. The strong statistical
      relationship between wind speed and both hornbill nest tree losses and household
      expenditures opens up an opportunity to design wind-based index insurance
      contracts that could both enhance hornbill conservation and support disaster
      affected households in the region. We demonstrate how such contracts could be
      written and operationalized and then use simulations to show the significant
      promise of unique insurance-based approaches to address weather-related risk that
      threatens both biodiversity and poor populations.

PMID- 21873184
TI  - Community Markets for Conservation (COMACO) links biodiversity conservation with
      sustainable improvements in livelihoods and food production.
AB  - In the Luangwa Valley, Zambia, persistent poverty and hunger present linked
      challenges to rural development and biodiversity conservation. Both household
      coping strategies and larger-scale economic development efforts have caused
      severe natural resource degradation that limits future economic opportunities and
      endangers ecosystem services. A model based on a business infrastructure has been
      developed to promote and maintain sustainable agricultural and natural resource
      management practices, leading to direct and indirect conservation outcomes. The
      Community Markets for Conservation (COMACO) model operates primarily with
      communities surrounding national parks, strengthening conservation benefits
      produced by these protected areas. COMACO first identifies the least food-secure
      households and trains them in sustainable agricultural practices that minimize
      threats to natural resources while meeting household needs. In addition, COMACO
      identifies people responsible for severe natural resource depletion and trains
      them to generate alternative income sources. In an effort to maintain compliance
      with these practices, COMACO provides extension support and access to high-value
      markets that would otherwise be inaccessible to participants. Because the model
      is continually evolving via adaptive management, success or failure of the model
      as a whole is difficult to quantify at this early stage. We therefore test
      specific hypotheses and present data documenting the stabilization of previously
      declining wildlife populations; the meeting of thresholds of productivity that
      give COMACO access to stable, high-value markets and progress toward economic
      self-sufficiency; and the adoption of sustainable agricultural practices by
      participants and other community members. Together, these findings describe a
      unique, business-oriented model for poverty alleviation, food production, and
      biodiversity conservation.

PMID- 21873185
TI  - Booming markets for Moroccan argan oil appear to benefit some rural households
      while threatening the endemic argan forest.
AB  - Morocco's argan oil is now the most expensive edible oil in the world. High-value
      argan markets have sparked a bonanza of argan activity. Nongovernmental
      organizations, international and domestic development agencies, and argan oil
      cooperatives aggressively promote the win-win aim of simultaneously benefiting
      local people and the health of the argan forest. This paper tests some of these
      win-win claims. Analysis of a panel of detailed household data suggests that the
      boom has enabled some rural households to increase consumption, increase their
      goat herds (which bodes poorly for the argan forest), and send their girls to
      secondary school. The boom has predictably made households vigilant guardians of
      fruit on the tree, but it has not incited investments in longer term tree and
      forest health. We evaluate landscape-level impacts of these changes using commune
      level data on educational enrollment and normalized difference vegetation index
      data over the period from 1981 to 2009. The results of the mesoanalysis of
      enrollment are consistent with the microanalysis: the argan boom seems to have
      improved educational outcomes, especially for girls. Our normalized difference
      vegetation index analysis, however, suggests that booming argan prices have not
      improved the forest and may have even induced degradation. We conclude by
      exploring the dynamic interactions between argan markets, local institutions,
      rural household welfare, and forest conservation and sustainability.

PMID- 21873190
TI  - Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and
      differentiation of hematopoietic stem cells in mice.
AB  - The Ten-Eleven-Translocation 2 (TET2) gene encodes a member of TET family enzymes
      that alters the epigenetic status of DNA by oxidizing 5-methylcytosine to 5
      hydroxymethylcytosine (5hmC). Somatic loss-of-function mutations of TET2 are
      frequently observed in patients with diverse myeloid malignancies, including
      myelodysplastic syndromes, myeloproliferative neoplasms, and chronic
      myelomonocytic leukemia. By analyzing mice with targeted disruption of the Tet2
      catalytic domain, we show here that Tet2 is a critical regulator of self-renewal
      and differentiation of hematopoietic stem cells (HSCs). Tet2 deficiency led to
      decreased genomic levels of 5hmC and augmented the size of the hematopoietic
      stem/progenitor cell pool in a cell-autonomous manner. In competitive
      transplantation assays, Tet2-deficient HSCs were capable of multilineage
      reconstitution and possessed a competitive advantage over wild-type HSCs,
      resulting in enhanced hematopoiesis into both lymphoid and myeloid lineages. In
      vitro, Tet2 deficiency delayed HSC differentiation and skewed development toward
      the monocyte/macrophage lineage. Our data indicate that Tet2 has a critical role
      in regulating the expansion and function of HSCs, presumably by controlling 5hmC
      levels at genes important for the self-renewal, proliferation, and
      differentiation of HSCs.

PMID- 21873191
TI  - Transcription factor AP4 modulates reversible and epigenetic silencing of the Cd4
      gene.
AB  - CD4 coreceptor expression is negatively regulated through activity of the Cd4
      silencer in CD4(-)CD8(-) double-negative (DN) thymocytes and CD8(+) cytotoxic
      lineage T cells. Whereas Cd4 silencing is reversed during transition from DN to
      CD4(+)CD8(+) double-positive stages, it is maintained through heritable
      epigenetic processes following its establishment in mature CD8(+) T cells. We
      previously demonstrated that the Runx family of transcription factors is required
      for Cd4 silencing both in DN thymocytes and CD8(+) T cells. However, additional
      factors that cooperate with Runx proteins in the process of Cd4 silencing remain
      unknown. To identify collaborating factors, we used microarray and RNAi-based
      approaches and found the basic helix-loop-helix ZIP transcription factor AP4 to
      have an important role in Cd4 regulation. AP4 interacts with Runx1 in cells in
      which Cd4 is silenced, and is required for Cd4 silencing in immature DN
      thymocytes through binding to the proximal enhancer. Furthermore, although AP4
      deficient CD8(+) T cells appeared to normally down-regulate CD4 expression, AP4
      deficiency significantly increased the frequency of CD4-expressing
      effector/memory CD8(+) T cells in mice harboring point mutations in the Cd4
      silencer. Our results suggest that AP4 contributes to Cd4 silencing both in DN
      and CD8(+) T cells by enforcing checkpoints for appropriate timing of CD4
      expression and its epigenetic silencing.

PMID- 21873193
TI  - Mobilization of natural killer cells inhibits development of collagen-induced
      arthritis.
AB  - Although natural killer (NK) cells have been implicated in regulating immune
      responses, their ability to modulate disease development in autoimmune arthritis
      has not been analyzed. Here we investigate the contribution of NK cells to
      regulating collagen-induced arthritis, a well-characterized preclinical model of
      human rheumatoid arthritis. We find that the disease is induced by the combined
      action of two CD4(+) T helper (T(H)) subsets: follicular T(H) cells and T(H)17
      cells. Both CD4(+) T(H) subsets are highly susceptible to lysis by NK cells after
      activation. Administration of antibody that activates NK cells through blockade
      of its inhibitory CD94/NKG2A receptor allows enhanced elimination of pathogenic
      follicular T(H) and T(H)17 cells and arrest of disease progression. These results
      suggest that antibody-dependent enhancement of NK activity may yield effective,
      previously undescribed therapeutic approaches to this autoimmune disorder.

PMID- 21873192
TI  - Transcriptional programs in transient embryonic zones of the cerebral cortex
      defined by high-resolution mRNA sequencing.
AB  - Characterizing the genetic programs that specify development and evolution of the
      cerebral cortex is a central challenge in neuroscience. Stem cells in the
      transient embryonic ventricular and subventricular zones generate neurons that
      migrate across the intermediate zone to the overlying cortical plate, where they
      differentiate and form the neocortex. It is clear that not one but a multitude of
      molecular pathways are necessary to progress through each cellular milestone, yet
      the underlying transcriptional programs remain unknown. Here, we apply
      differential transcriptome analysis on microscopically isolated cell populations,
      to define five transcriptional programs that represent each transient embryonic
      zone and the progression between these zones. The five transcriptional programs
      contain largely uncharacterized genes in addition to transcripts necessary for
      stem cell maintenance, neurogenesis, migration, and differentiation.
      Additionally, we found intergenic transcriptionally active regions that possibly
      encode unique zone-specific transcripts. Finally, we present a high-resolution
      transcriptome map of transient zones in the embryonic mouse forebrain.

PMID- 21873194
TI  - Recombinant Rift Valley fever vaccines induce protective levels of antibody in
      baboons and resistance to lethal challenge in mice.
AB  - Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian
      Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can
      be lethal to humans and animals and results in major losses in the livestock
      industry. RVF is exotic to the United States; however, mosquito species native to
      this region can serve as biological vectors for the virus. Thus, accidental or
      malicious introduction of this virus could result in RVFV becoming endemic in
      North America. Such an event would likely lead to significant morbidity and
      mortality in humans, and devastating economic effects on the livestock industry.
      Currently, there are no licensed vaccines for RVF that are both safe and
      efficacious. To address this issue, we developed two recombinant RVFV vaccines
      using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine,
      vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-gamma
      binding protein, insertional inactivation of the thymidine kinase gene, and
      expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcgamma, is
      identical to the first and also expresses the human IFN-gamma gene to enhance
      safety. Both vaccines are extremely safe; neither resulted in weight loss nor
      death in severe combined immunodeficient mice, and pock lesions were smaller in
      baboons compared with the controls. Furthermore, both vaccines induced protective
      levels of antibody titers in vaccinated mice and baboons. Mice were protected
      from lethal RVFV challenge. Thus, we have developed two safe and efficacious
      recombinant vaccines for RVF.

PMID- 21873195
TI  - Interleukin 37 expression protects mice from colitis.
AB  - IL-37, a newly described member of the IL-1 family, functions as a fundamental
      inhibitor of innate inflammation and immunity. In the present study, we examined
      a role for IL-37 during experimental colitis. A transgenic mouse strain was
      generated to express human IL-37 (hIL-37tg), and these mice were subjected to
      dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV
      promoter to drive expression of IL-37, mRNA transcripts were not present in
      colons at the resting state. Expression was observed only upon disruption of the
      epithelial barrier, with a six- to sevenfold increase (P = 0.02) on days 3 and 5
      after continuous exposure to DSS. During the development of colitis, clinical
      disease scores were reduced by 50% (P < 0.001), and histological indices of
      colitis were one-third less in hIL-37tg mice compared with WT counterparts (P <
      0.001). Reduced inflammation was associated with decreased leukocyte recruitment
      into the colonic lamina propria. In addition, release of IL-1beta and TNFalpha
      from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively,
      compared with WT (P <= 0.005), whereas IL-10 was increased sixfold (P < 0.001).
      However, IL-10 was not required for the anti-inflammatory effects of IL-37
      because IL-10-receptor antibody blockade did not reverse IL-37-mediated
      protection. Mechanistically, IL-37 originating from hematopoietic cells was
      sufficient to exert anti-inflammatory effects because WT mice reconstituted with
      hIL-37tg bone marrow were protected from colitis. Thus, IL-37 emerges as key
      modulator of intestinal inflammation.

PMID- 21873196
TI  - Concerted action of two avirulent spore effectors activates Reaction to Puccinia
      graminis 1 (Rpg1)-mediated cereal stem rust resistance.
AB  - The barley stem rust resistance gene Reaction to Puccinia graminis 1 (Rpg1),
      encoding a receptor-like kinase, confers durable resistance to the stem rust
      pathogen Puccinia graminis f. sp. tritici. The fungal urediniospores form
      adhesion structures with the leaf epidermal cells within 1 h of inoculation,
      followed by hyphae and haustorium formation. The RPG1 protein is constitutively
      expressed and not phosphorylated. On inoculation with avirulent urediniospores,
      it is phosphorylated in vivo within 5 min and subsequently degraded. Application
      of arginine-glycine-aspartic acid peptide loops prevented the formation of
      adhesion structures for spore attachment, the phosphorylation of RPG1, and
      germination of the viable spores. Arginine-glycine-aspartic acid affinity
      chromatography of proteins from the ungerminated avirulent rust spores led to the
      purification and identification of a protein with fibronectin type III and breast
      cancer type 1 susceptibility protein domains and a vacuolar protein sorting
      associated protein 9 with a coupling of ubiquitin to endoplasmic reticulum
      degradation domain. Both proteins are required to induce in vivo phosphorylation
      and degradation of RPG1. Combined application of both proteins caused
      hypersensitive reaction on the stem rust-resistant cultivar Morex but not on the
      susceptible cultivar Steptoe. Expression studies indicated that mRNA of both
      genes are present in ungerminated urediniospores and are constitutively
      transcribed in sporelings, infected leaves, and haustoria in the investigated
      avirulent races. Evidence is presented that RPG1, in yeast, interacts with the
      two protein effectors from the urediniospores that activate cooperatively the
      stem rust resistance protein RPG1 long before haustoria formation.

PMID- 21873197
TI  - Long-range pseudoknot interactions dictate the regulatory response in the
      tetrahydrofolate riboswitch.
AB  - Tetrahydrofolate (THF), a biologically active form of the vitamin folate (B(9)),
      is an essential cofactor in one-carbon transfer reactions. In bacteria,
      expression of folate-related genes is controlled by feedback modulation in
      response to specific binding of THF and related compounds to a riboswitch. Here,
      we present the X-ray structures of the THF-sensing domain from the Eubacterium
      siraeum riboswitch in the ligand-bound and unbound states. The structure reveals
      an "inverted" three-way junctional architecture, most unusual for riboswitches,
      with the junction located far from the regulatory helix P1 and not directly
      participating in helix P1 formation. Instead, the three-way junction, stabilized
      by binding to the ligand, aligns the riboswitch stems for long-range tertiary
      pseudoknot interactions that contribute to the organization of helix P1 and
      therefore stipulate the regulatory response of the riboswitch. The pterin moiety
      of the ligand docks in a semiopen pocket adjacent to the junction, where it forms
      specific hydrogen bonds with two moderately conserved pyrimidines. The
      aminobenzoate moiety stacks on a guanine base, whereas the glutamate moiety does
      not appear to make strong interactions with the RNA. In contrast to other
      riboswitches, these findings demonstrate that the THF riboswitch uses a limited
      number of available determinants for ligand recognition. Given that modern
      antibiotics target folate metabolism, the THF riboswitch structure provides
      insights on mechanistic aspects of riboswitch function and may help in
      manipulating THF levels in pathogenic bacteria.

PMID- 21873198
TI  - Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN)
      ectodomain reveals a four-helix bundle stalk.
AB  - The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles
      in viral entry and egress, including binding to sialic acid receptors, activating
      the fusion (F) protein to activate membrane fusion and viral entry, and cleaving
      sialic acid from carbohydrate chains. HN is an oligomeric integral membrane
      protein consisting of an N-terminal transmembrane domain, a stalk region, and an
      enzymatically active neuraminidase (NA) domain. Structures of the HN NA domains
      have been solved previously; however, the structure of the stalk region has
      remained elusive. The stalk region contains specificity determinants for F
      interactions and activation, underlying the requirement for homotypic F and HN
      interactions in viral entry. Mutations of the Newcastle disease virus HN stalk
      region have been shown to affect both F activation and NA activities, but a
      structural basis for understanding these dual affects on HN functions has been
      lacking. Here, we report the structure of the Newcastle disease virus HN
      ectodomain, revealing dimers of NA domain dimers flanking the N-terminal stalk
      domain. The stalk forms a parallel tetrameric coiled-coil bundle (4HB) that
      allows classification of extensive mutational data, providing insight into the
      functional roles of the stalk region. Mutations that affect both F activation and
      NA activities map predominantly to the 4HB hydrophobic core, whereas mutations
      that affect only F-protein activation map primarily to the 4HB surface. Two of
      four NA domains interact with the 4HB stalk, and residues at this interface in
      both the stalk and NA domain have been implicated in HN function.

PMID- 21873200
TI  - Membrane tension leads the way.

PMID- 21873199
TI  - Minimization of the Legionella pneumophila genome reveals chromosomal regions
      involved in host range expansion.
AB  - Legionella pneumophila is a bacterial pathogen of amoebae and humans.
      Intracellular growth requires a type IVB secretion system that translocates at
      least 200 different proteins into host cells. To distinguish between proteins
      necessary for growth in culture and those specifically required for intracellular
      replication, a screen was performed to identify genes necessary for optimal
      growth in nutrient-rich medium. Mapping of these genes revealed that the L.
      pneumophila chromosome has a modular architecture consisting of several large
      genomic islands that are dispensable for growth in bacteriological culture.
      Strains lacking six of these regions, and thus 18.5% of the genome, were viable
      but required secondary point mutations for optimal growth. The simultaneous
      deletion of five of these genomic loci had no adverse effect on growth of the
      bacterium in nutrient-rich media. Remarkably, this minimal genome strain, which
      lacked 31% of the known substrates of the type IVB system, caused only marginal
      defects in intracellular growth within mouse macrophages. In contrast, deletion
      of single regions reduced growth within amoebae. The importance of individual
      islands, however, differed among amoebal species. The host-specific requirements
      of these genomic islands support a model in which the acquisition of foreign DNA
      has broadened the L. pneumophila host range.

PMID- 21873201
TI  - Himalayan glaciers: the big picture is a montage.

PMID- 21873202
TI  - (Compressed) sensing and sensibility.

PMID- 21873203
TI  - Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during
      oogenesis.
AB  - N(6)-methyladenosine is a nonediting RNA modification found in mRNA of all
      eukaryotes, from yeast to humans. Although the functional significance of N(6)
      methyladenosine is unknown, the Inducer of MEiosis 4 (IME4) gene of Saccharomyces
      cerevisiae, which encodes the enzyme that catalyzes this modification, is
      required for gametogenesis. Here we find that the Drosophila IME4 homolog, Dm
      ime4, is expressed in ovaries and testes, indicating an evolutionarily conserved
      function for this enzyme in gametogenesis. In contrast to yeast, but as in
      Arabidopsis, Dm ime4 is essential for viability. Lethality is rescued fully by a
      wild-type transgenic copy of Dm ime4 but not by introducing mutations shown to
      abrogate the catalytic activity of yeast Ime4, indicating functional conservation
      of the catalytic domain. The phenotypes of hypomorphic alleles of Dm ime4 that
      allow recovery of viable adults reveal critical functions for this gene in
      oogenesis. Ovarioles from Dm ime4 mutants have fused egg chambers with follicle
      cell defects similar to those observed when Notch signaling is defective. Indeed,
      using a reporter for Notch activation, we find markedly reduced levels of Notch
      signaling in follicle cells of Dm ime4 mutants. This phenotype of Dm ime4 mutants
      is rescued by inducing expression of a constitutively activated form of Notch.
      Our study reveals the function of IME4 in a metazoan. In yeast, this enzyme is
      responsible for a crucial developmental decision, whereas in Drosophila it
      appears to target the conserved Notch signaling pathway, which regulates many
      vital aspects of metazoan development.

PMID- 21873204
TI  - Bacterial community comparisons by taxonomy-supervised analysis independent of
      sequence alignment and clustering.
AB  - High-throughput sequencing of 16S rRNA genes has increased our understanding of
      microbial community structure, but now even higher-throughput methods to the
      Illumina scale allow the creation of much larger datasets with more samples and
      orders-of-magnitude more sequences that swamp current analytic methods. We
      developed a method capable of handling these larger datasets on the basis of
      assignment of sequences into an existing taxonomy using a supervised learning
      approach (taxonomy-supervised analysis). We compared this method with a commonly
      used clustering approach based on sequence similarity (taxonomy-unsupervised
      analysis). We sampled 211 different bacterial communities from various habitats
      and obtained ~1.3 million 16S rRNA sequences spanning the V4 hypervariable region
      by pyrosequencing. Both methodologies gave similar ecological conclusions in that
      beta-diversity measures calculated by using these two types of matrices were
      significantly correlated to each other, as were the ordination configurations and
      hierarchical clustering dendrograms. In addition, our taxonomy-supervised
      analyses were also highly correlated with phylogenetic methods, such as UniFrac.
      The taxonomy-supervised analysis has the advantages that it is not limited by the
      exhaustive computation required for the alignment and clustering necessary for
      the taxonomy-unsupervised analysis, is more tolerant of sequencing errors, and
      allows comparisons when sequences are from different regions of the 16S rRNA
      gene. With the tremendous expansion in 16S rRNA data acquisition underway, the
      taxonomy-supervised approach offers the potential to provide more rapid and
      extensive community comparisons across habitats and samples.

PMID- 21873206
TI  - Olfactory habituation: fresh insights from flies.

PMID- 21873205
TI  - Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via
      altered mitochondrial oxidation and reactive oxygen species production.
AB  - Sirt3 is a member of the sirtuin family of protein deacetylases that is localized
      in mitochondria and regulates mitochondrial function. Sirt3 expression in
      skeletal muscle is decreased in models of type 1 and type 2 diabetes and
      regulated by feeding, fasting, and caloric restriction. Sirt3 knockout mice
      exhibit decreased oxygen consumption and develop oxidative stress in skeletal
      muscle, leading to JNK activation and impaired insulin signaling. This effect is
      mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced
      mitochondrial oxidation, increased reactive oxygen species, activation of JNK,
      increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased
      insulin signaling. Thus, Sirt3 plays an important role in diabetes through
      regulation of mitochondrial oxidation, reactive oxygen species production, and
      insulin resistance in skeletal muscle.

PMID- 21873207
TI  - Multilevel autoregulation of lambda repressor protein CI by DNA looping in vitro.
AB  - The prophage state of bacteriophage lambda is extremely stable and is maintained
      by a highly regulated level of lambda repressor protein, CI, which represses
      lytic functions. CI regulates its own synthesis in a lysogen by activating and
      repressing its promoter, P(RM). CI participates in long-range interactions
      involving two regions of widely separated operator sites by generating a loop in
      the intervening DNA. We investigated the roles of each individual site under
      conditions that permitted DNA loop formation by using in vitro transcription
      assays for the first time on supercoiled DNA that mimics in vivo situation. We
      confirmed that DNA loops generated by oligomerization of CI bound to its
      operators influence the autoactivation and autorepression of P(RM) regulation. We
      additionally report that different configurations of DNA loops are central to
      this regulation--one configuration further enhances autoactivation and another is
      essential for autorepression of P(RM).

PMID- 21873208
TI  - Dynamic fluctuations lubricate the circadian clock.

PMID- 21873209
TI  - Transcription factor RBPJ/CSL: a genome-wide look at transcriptional regulation.

PMID- 21873210
TI  - High-temperature high-pressure phases of lithium from electron force field (eFF)
      quantum electron dynamics simulations.
AB  - We recently developed the electron force field (eFF) method for practical
      nonadiabatic electron dynamics simulations of materials under extreme conditions
      and showed that it gave an excellent description of the shock thermodynamics of
      hydrogen from molecules to atoms to plasma, as well as the electron dynamics of
      the Auger decay in diamondoids following core electron ionization. Here we apply
      eFF to the shock thermodynamics of lithium metal, where we find two distinct
      consecutive phase changes that manifest themselves as a kink in the shock
      Hugoniot, previously observed experimentally, but not explained. Analyzing the
      atomic distribution functions, we establish that the first phase transition
      corresponds to (i) an fcc-to-cI16 phase transition that was observed previously
      in diamond anvil cell experiments at low temperature and (ii) a second phase
      transition that corresponds to the formation of a new amorphous phase (amor) of
      lithium that is distinct from normal molten lithium. The amorphous phase has
      enhanced valence electron-nucleus interactions due to localization of electrons
      into interstitial locations, along with a random connectivity distribution
      function. This indicates that eFF can characterize and compute the relative
      stability of states of matter under extreme conditions (e.g., warm dense matter).

PMID- 21873211
TI  - Nuclear receptor chicken ovalbumin upstream promoter-transcription factor II
      (COUP-TFII) modulates mesenchymal cell commitment and differentiation.
AB  - The mesenchymal cell is a multipotent stem cell with the capacity to give rise to
      multiple cell types such as adipocytes, osteoblasts, chondrocytes, and myocytes.
      However, the molecular events responsible for their lineage specification and
      differentiation remain obscure. Here we show that inactivation of chicken
      ovalbumin upstream promoter-transcription factor II (COUP-TFII), a member of the
      nuclear receptor superfamily, in mesenchymal progenitors favors osteoblast and
      myoblast development while simultaneously impairing adipogenic and chondrogenic
      programs. During mouse embryogenesis, COUP-TFII protein is highly detected in the
      mesenchymal compartment and is involved in mesoderm tissue formation. Ablation of
      COUP-TFII in mice led to higher bone density, increased muscle mass, and
      suppression of cartilage and fat formation. We further demonstrate that COUP-TFII
      directs the plasticity of mesenchymal precursors primarily through the combined
      modulation of Wnt signaling, Runx2 activity, as well as PPARgamma and Sox9
      expression. Together, our results provide insight into the mechanisms whereby a
      single nuclear receptor can fine-tune the lineage-specific differentiation of a
      progenitor cell.

PMID- 21873212
TI  - Optical imaging in galagos reveals parietal-frontal circuits underlying motor
      behavior.
AB  - The posterior parietal cortex (PPC) of monkeys and prosimian galagos contains a
      number of subregions where complex, behaviorally meaningful movements, such as
      reaching, grasping, and body defense, can be evoked by electrical stimulation
      with long trains of electrical pulses through microelectrodes. Shorter trains of
      pulses evoke no or simple movements. One possibility for the difference in
      effectiveness of intracortical microstimulation is that long trains activate much
      larger regions of the brain. Here, we show that long-train stimulation of PPC
      does not activate widespread regions of frontal motor and premotor cortex but
      instead, produces focal, somatotopically appropriate activations of frontal motor
      and premotor cortex. Shorter stimulation trains activate the same frontal foci
      but less strongly, showing that longer stimulus trains do not produce less
      specification. Because the activated sites in frontal cortex correspond to the
      locations of direct parietal-frontal anatomical connections from the stimulated
      PPC subregions, the results show the usefulness of optical imaging in conjunction
      with electrical stimulation in showing functional pathways between nodes in
      behavior-specific cortical networks. Thus, long-train stimulation is effective in
      evoking ethologically relevant sequences of movements by activating nodes in a
      cortical network for a behaviorally relevant period rather than spreading
      activation in a nonspecific manner.

PMID- 21873213
TI  - Quantitative impact of thymic selection on Foxp3+ and Foxp3- subsets of self
      peptide/MHC class II-specific CD4+ T cells.
AB  - It is currently thought that T cells with specificity for self-peptide/MHC (pMHC)
      ligands are deleted during thymic development, thereby preventing autoimmunity.
      In the case of CD4(+) T cells, what is unclear is the extent to which self
      peptide/MHC class II (pMHCII)-specific T cells are deleted or become Foxp3(+)
      regulatory T cells. We addressed this issue by characterizing a natural
      polyclonal pMHCII-specific CD4(+) T-cell population in mice that either lacked or
      expressed the relevant antigen in a ubiquitous pattern. Mice expressing the
      antigen contained one-third the number of pMHCII-specific T cells as mice lacking
      the antigen, and the remaining cells exhibited low TCR avidity. In mice lacking
      the antigen, the pMHCII-specific T-cell population was dominated by
      phenotypically naive Foxp3(-) cells, but also contained a subset of Foxp3(+)
      regulatory cells. Both Foxp3(-) and Foxp3(+) pMHCII-specific T-cell numbers were
      reduced in mice expressing the antigen, but the Foxp3(+) subset was more
      resistant to changes in number and TCR repertoire. Therefore, thymic selection of
      self-pMHCII-specific CD4(+) T cells results in incomplete deletion within the
      normal polyclonal repertoire, especially among regulatory T cells.

PMID- 21873214
TI  - Site-directed tryptophan fluorescence reveals two essential conformational
      changes in the Na+/H+ antiporter NhaA.
AB  - NhaA, a Na(+)/H(+) antiporter critical for pH and Na(+) homeostasis in
      Escherichia coli, as well as other enterobacteria and possibly Homo sapiens, was
      modified for fluorescence spectroscopy by constructing a functional Trp-less NhaA
      mutant. Purified Trp-less NhaA lacks the Trp fluorescence emission characteristic
      of the wild type, thereby providing a background for studying structure-function
      relationships in NhaA by site-directed Trp fluorescence. Two single-Trp variants
      in the Trp-less background (F136W and F339W) were constructed. The mutants grow
      on selective media, have antiport activities that are similar to Trp-less NhaA,
      and exhibit Trp fluorescence with three different reversible responses to Li(+),
      Na(+), and/or pH. With single Trp/F136W, a pH shift from pH 6.0 to 8.5 induces a
      red shift and dramatically increases fluorescence in a reversible fashion; no
      effect is observed when either Na(+) or Li(+) is added. In marked contrast, with
      single Trp/F339W, changes in pH do not alter fluorescence, but addition of either
      Na(+) or Li(+) drastically quenches fluorescence at alkaline pH. Therefore, a Trp
      at position 136 specifically monitors a pH-induced conformational change that
      activates NhaA, whereas a Trp at position 339 senses a ligand-induced
      conformational change that does not occur until NhaA is activated at alkaline pH.

PMID- 21873216
TI  - A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle
      biogenesis and adaptive flotation in an enterobacterium.
AB  - Gas vesicles are hollow intracellular proteinaceous organelles produced by
      aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas
      vesicles increase buoyancy and allow taxis toward air-liquid interfaces, enabling
      subsequent niche colonization. Here we report a unique example of gas vesicle
      mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This
      strain is a member of the Enterobacteriaceae previously studied for its
      production of prodigiosin and carbapenem antibiotics. Genes required for gas
      vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct
      homologs of the main structural protein, GvpA. Heterologous expression of this
      locus in Escherichia coli induced copious vesicle production and efficient cell
      buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle
      like layer of highly vacuolated cells, which was dependent on oxygen limitation
      and the expression of ntrB/C and cheY-like regulatory genes within the gas
      vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by
      intercellular chemical signaling, through an N-acyl homoserine lactone,
      indicating that in this system the quorum-sensing molecule acts as a morphogen
      initiating organelle development. Flagella-based motility and gas vesicle
      morphogenesis were also oppositely regulated by the small RNA-binding protein,
      RsmA, suggesting environmental adaptation through physiological control of the
      choice between motility and flotation as alternative taxis modes. We propose that
      gas vesicle biogenesis in this strain represents a distinct mechanism of
      mobility, regulated by oxygen availability, nutritional status, the RsmA global
      regulatory system, and the quorum-sensing morphogen.

PMID- 21873215
TI  - Estrogen receptor alpha AF-2 mutation results in antagonist reversal and reveals
      tissue selective function of estrogen receptor modulators.
AB  - The estrogen receptor (ER) is a ligand-dependent transcription factor containing
      two transcriptional activation domains. AF-1 is in the N terminus of the receptor
      protein and AF-2 activity is dependent on helix 12 of the C-terminal ligand
      binding domain. Two point mutations of leucines 543 and 544 to alanines (L543A,
      L544A) in helix 12 minimized estrogen-dependent transcriptional activation and
      reversed the activity of the estrogen antagonists ICI182780 (ICI) and tamoxifen
      (TAM) into agonists in a similar manner that TAM activated WT ERalpha through AF
      1 activation. To evaluate the physiological role of AF-1 and AF-2 for the tissue
      selective function of TAM, we generated an AF-2-mutated ERalpha knock-in
      (AF2ERKI) mouse model. AF2ERKI homozygote female mice have hypoplastic uterine
      tissue and rudimentary mammary glands similar to ERalpha-KO mice. Female mice
      were infertile as a result of anovulation from hemorrhagic cystic ovaries and
      elevated serum LH and E2 levels, although the mutant ERalpha protein is expressed
      in the AF2ERKI model. The AF2ERKI phenotype suggests that AF-1 is not activated
      independently, even with high serum E2 levels. ICI and TAM induced uterotropic
      and ER-mediated gene responses in ovariectomized AF2ERKI female mice in the same
      manner as in TAM- and E2-treated WT mice. In contrast, ICI and TAM did not act as
      agonists to regulate negative feedback of serum LH or stimulate pituitary
      prolactin gene expression in a different manner than TAM- or E2-treated WT mice.
      The functionality of the mutant ERalpha in the pituitary appears to be different
      from that in the uterus, indicating that ERalpha uses AF-1 differently in the
      uterus and the pituitary for TAM action.

PMID- 21873217
TI  - Cranial asymmetry in Eocene archaeocete whales and the evolution of directional
      hearing in water.
AB  - Eocene archaeocete whales gave rise to all modern toothed and baleen whales
      (Odontoceti and Mysticeti) during or near the Eocene-Oligocene transition.
      Odontocetes have asymmetrical skulls, with asymmetry linked to high-frequency
      sound production and echolocation. Mysticetes are generally assumed to have
      symmetrical skulls and lack high-frequency hearing. Here we show that protocetid
      and basilosaurid archaeocete skulls are distinctly and directionally
      asymmetrical. Archaeocete asymmetry involves curvature and axial torsion of the
      cranium, but no telescoping. Cranial asymmetry evolved in Eocene archaeocetes as
      part of a complex of traits linked to directional hearing (such as pan-bone
      thinning of the lower jaws, mandibular fat pads, and isolation of the ear
      region), probably enabling them to hear the higher sonic frequencies of sound
      producing fish on which they preyed. Ultrasonic echolocation evolved in Oligocene
      odontocetes, enabling them to find silent prey. Asymmetry and much of the sonic
      frequency range of directional hearing were lost in Oligocene mysticetes during
      the shift to low-frequency hearing and bulk-straining predation.

PMID- 21873218
TI  - CD4+ T cells from elite suppressors are more susceptible to HIV-1 but produce
      fewer virions than cells from chronic progressors.
AB  - Elite suppressors/controllers (ES) are HIV-1-infected individuals who maintain
      stable CD4(+) T-cell counts and viral loads of <50 copies/mL without
      antiretroviral therapy. Research has predominantly focused on immune factors
      contributing to the control of viral replication in these patients. A more
      fundamental question, however, is whether there are differences in the nature of
      CD4(+) T-cell infection in ES compared with viremic patients. Here, we compare
      chronic progressor (CP), ES, and uninfected donors in terms of three aspects of
      CD4(+) T-cell infection: cellular susceptibility to infection, death of infected
      cells, and production of virus from infected cells. Using multiple methods of
      infection and both single-cycle and replication-competent virus, we show that
      unmanipulated CD4(+) T-cell populations from ES are actually more susceptible to
      HIV-1 infection than those populations from CP. Depletion of highly susceptible
      cells in CP may contribute to this difference. Using 7AAD and AnnexinV staining,
      we show that infected cells die more rapidly than uninfected cells, but the
      increased death of infected cells from CP and ES is proportional. Finally, using
      an assay for measuring virus production, we show that virus production by cells
      from CP is high compared with virus production by cells from ES or uninfected
      donors. This higher virus production is linked to cellular activation levels.
      These data identify fundamental differences in chronic infection of ES and CP
      that likely contribute to differential HIV-1 disease progression.

PMID- 21873219
TI  - The central cavity in trimeric glutamate transporters restricts ligand diffusion.
AB  - A prominent aqueous cavity is formed by the junction of three identical subunits
      in the excitatory amino acid transporter (EAAT) family. To investigate the effect
      of this structure on the interaction of ligands with the transporter, we recorded
      currents in voltage-clamped Xenopus oocytes expressing EAATs and used
      concentration jumps to measure binding and unbinding rates of a high-affinity
      aspartate analog that competitively blocks transport (beta-2-fluorenyl
      aspartylamide; 2-FAA). The binding rates of the blocker were approximately one
      order of magnitude slower than l-Glu and were not significantly different for
      EAAT1, EAAT2, or EAAT3, but 2-FAA exhibited higher affinity for the neuronal
      transporter EAAT3 as a result of a slower dissociation rate. Unexpectedly, the
      rate of recovery from block was increased by l-Glu in a saturable and
      concentration-dependent manner, ruling out a first-order mechanism and suggesting
      that following unbinding, there is a significant probability of ligand rebinding
      to the same or neighboring subunits within a trimer. Consistent with such a
      mechanism, coexpression of wild-type subunits with mutant (R447C) subunits that
      do not bind glutamate or 2-FAA also increased the unblocking rate. The data
      suggest that electrostatic and steric factors result in an effective dissociation
      rate that is approximately sevenfold slower than the microscopic subunit
      unbinding rate. The quaternary structure, which has been conserved through
      evolution, is expected to increase the transporters' capture efficiency by
      increasing the probability that following unbinding, a ligand will rebind as
      opposed to being lost to diffusion.

PMID- 21873220
TI  - Racemization as a stereochemical measure of dynamics and robustness in shape
      shifting organic molecules.
AB  - Bullvalene is a structurally unique dynamic molecule thought to interconvert
      among 1.2 million degenerate isomers. The incorporation of different chemical
      substituents onto the bullvalene core should lead to a "shape-shifting" molecule
      that can interconvert among thousands of discrete structural isomers. Previous
      NMR spectroscopy and HPLC studies on substituted bullvalenes ascertained the fact
      that these compounds are dynamic, but they could not attest to whether the
      molecules are only interconverting among only a few isomers or if a multitude of
      structures are being accessed. Here we confirm the remarkable shape-shifting
      property of a tetrasubstituted bullvalene by means of a racemization experiment.
      We show that a single, though fleeting, chiral, enantioenriched tetrasubstituted
      bullvalene isomer can spontaneously equilibrate to a racemic population of
      dynamic compounds. Despite the fact that conversion from one enantiomer of a
      bullvalene isomer to the other may require dozens or even hundreds of
      rearrangements and involve many potential pathways, CD spectroscopy and HPLC
      analysis of different bullvalene populations showed that multiple pathways exist
      and result in the complete racemization of an initial enantioenriched chiral
      bullvalene. These oligosubstituted bullvalenes represent a very rare example of
      an entity that can spontaneously transform itself into different discrete
      structures using ambient thermal energy. The confirmation that these shape
      shifting organic molecules are chemically robust yet structurally dynamic is an
      important step toward their further use as materials, sensors, and biologically
      active compounds.

PMID- 21873221
TI  - Age-related changes in the plasticity and toughness of human cortical bone at
      multiple length scales.
AB  - The structure of human cortical bone evolves over multiple length scales from its
      basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal
      structures at near-millimeter dimensions, which all provide the basis for its
      mechanical properties. To resist fracture, bone's toughness is derived
      intrinsically through plasticity (e.g., fibrillar sliding) at structural scales
      typically below a micrometer and extrinsically (i.e., during crack growth)
      through mechanisms (e.g., crack deflection/bridging) generated at larger
      structural scales. Biological factors such as aging lead to a markedly increased
      fracture risk, which is often associated with an age-related loss in bone mass
      (bone quantity). However, we find that age-related structural changes can
      significantly degrade the fracture resistance (bone quality) over multiple length
      scales. Using in situ small-angle X-ray scattering and wide-angle X-ray
      diffraction to characterize submicrometer structural changes and synchrotron X
      ray computed tomography and in situ fracture-toughness measurements in the
      scanning electron microscope to characterize effects at micrometer scales, we
      show how these age-related structural changes at differing size scales degrade
      both the intrinsic and extrinsic toughness of bone. Specifically, we attribute
      the loss in toughness to increased nonenzymatic collagen cross-linking, which
      suppresses plasticity at nanoscale dimensions, and to an increased osteonal
      density, which limits the potency of crack-bridging mechanisms at micrometer
      scales. The link between these processes is that the increased stiffness of the
      cross-linked collagen requires energy to be absorbed by "plastic" deformation at
      higher structural levels, which occurs by the process of microcracking.

PMID- 21873222
TI  - Three-dimensional structure and function of the Paramecium bursaria chlorella
      virus capsid.
AB  - A cryoelectron microscopy 8.5 A resolution map of the 1,900 A diameter,
      icosahedral, internally enveloped Paramecium bursaria chlorella virus was used to
      interpret structures of the virus at initial stages of cell infection. A fivefold
      averaged map demonstrated that two minor capsid proteins involved in stabilizing
      the capsid are missing in the vicinity of the unique vertex. Reconstruction of
      the virus in the presence of host chlorella cell walls established that the spike
      at the unique vertex initiates binding to the cell wall, which results in the
      enveloped nucleocapsid moving closer to the cell. This process is concurrent with
      the release of the internal viral membrane that was linked to the capsid by many
      copies of a viral membrane protein in the mature infectous virus. Simultaneously,
      part of the trisymmetrons around the unique vertex disassemble, probably in part
      because two minor capsid proteins are absent, causing Paramecium bursaria
      chlorella virus and the cellular contents to merge, possibly as a result of
      enzyme(s) within the spike assembly. This may be one of only a few recordings of
      successive stages of a virus while infecting a eukaryotic host in pseudoatomic
      detail in three dimensions.

PMID- 21873223
TI  - Phylogenetic rate shifts in feeding time during the evolution of Homo.
AB  - Unique among animals, humans eat a diet rich in cooked and nonthermally processed
      food. The ancestors of modern humans who invented food processing (including
      cooking) gained critical advantages in survival and fitness through increased
      caloric intake. However, the time and manner in which food processing became
      biologically significant are uncertain. Here, we assess the inferred evolutionary
      consequences of food processing in the human lineage by applying a Bayesian
      phylogenetic outlier test to a comparative dataset of feeding time in humans and
      nonhuman primates. We find that modern humans spend an order of magnitude less
      time feeding than predicted by phylogeny and body mass (4.7% vs. predicted 48% of
      daily activity). This result suggests that a substantial evolutionary rate change
      in feeding time occurred along the human branch after the human-chimpanzee split.
      Along this same branch, Homo erectus shows a marked reduction in molar size that
      is followed by a gradual, although erratic, decline in H. sapiens. We show that
      reduction in molar size in early Homo (H. habilis and H. rudolfensis) is
      explicable by phylogeny and body size alone. By contrast, the change in molar
      size to H. erectus, H. neanderthalensis, and H. sapiens cannot be explained by
      the rate of craniodental and body size evolution. Together, our results indicate
      that the behaviorally driven adaptations of food processing (reduced feeding time
      and molar size) originated after the evolution of Homo but before or concurrent
      with the evolution of H. erectus, which was around 1.9 Mya.

PMID- 21873224
TI  - Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala
      (EPIYA) motif that is exploited by bacterial effectors.
AB  - Several pathogenic bacteria have adopted effector proteins that, upon delivery
      into mammalian cells, undergo tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala
      (EPIYA) or EPIYA-like sequence motif by host kinases such as Src family kinases
      (SFKs). This EPIYA phosphorylation triggers complex formation of bacterial
      effectors with SH2 domain-containing proteins that results in perturbation of
      host cell signaling and subsequent pathogenesis. Although the presence of such an
      anomalous protein interaction suggests the existence of a mammalian EPIYA
      containing protein whose function is mimicked or subverted by bacterial EPIYA
      effectors, no molecule that uses the EPIYA motif for biological function has so
      far been reported in mammals. Here we show that mammalian Pragmin/SgK223
      undergoes tyrosine phosphorylation at the EPIYA motif by SFKs and thereby
      acquires the ability to interact with the SH2 domain of the C-terminal Src kinase
      (Csk), a negative regulator of SFKs. The Pragmin-Csk interaction prevents
      translocalization of Csk from the cytoplasm to the membrane and subsequent
      inactivation of membrane-associated SFKs. As a result, SFK activity is sustained
      in cells where Pragmin is phosphorylated at the EPIYA motif. Because EPIYA
      phosphorylation of Pragmin is mediated by SFKs, cytoplasmic sequestration of Csk
      by Pragmin establishes a positive feedback regulation of SFK activation.
      Remarkably, the Helicobacter pylori EPIYA effector CagA binds to the Csk SH2
      domain in place of Pragmin and enforces membrane recruitment of Csk and
      subsequent inhibition of SFKs. This work identifies Pragmin as a mammalian EPIYA
      effector and suggests that bacterial EPIYA effectors target Pragmin to subvert
      SFKs for successful infection.

PMID- 21873225
TI  - Serotonin signaling is associated with lower amyloid-beta levels and plaques in
      transgenic mice and humans.
AB  - Aggregation of amyloid-beta (Abeta) as toxic oligomers and amyloid plaques within
      the brain appears to be the pathogenic event that initiates Alzheimer's disease
      (AD) lesions. One therapeutic strategy has been to reduce Abeta levels to limit
      its accumulation. Activation of certain neurotransmitter receptors can regulate
      Abeta metabolism. We assessed the ability of serotonin signaling to alter brain
      Abeta levels and plaques in a mouse model of AD and in humans. In mice, brain
      interstitial fluid (ISF) Abeta levels were decreased by 25% following
      administration of several selective serotonin reuptake inhibitor (SSRI)
      antidepressant drugs. Similarly, direct infusion of serotonin into the
      hippocampus reduced ISF Abeta levels. Serotonin-dependent reductions in Abeta
      were reversed if mice were pretreated with inhibitors of the extracellular
      regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI,
      citalopram, caused a 50% reduction in brain plaque load in mice. To test whether
      serotonin signaling could impact Abeta plaques in humans, we retrospectively
      compared brain amyloid load in cognitively normal elderly participants who were
      exposed to antidepressant drugs within the past 5 y to participants who were not.
      Antidepressant-treated participants had significantly less amyloid load as
      quantified by positron emission tomography (PET) imaging with Pittsburgh Compound
      B (PIB). Cumulative time of antidepressant use within the 5-y period preceding
      the scan correlated with less plaque load. These data suggest that serotonin
      signaling was associated with less Abeta accumulation in cognitively normal
      individuals.

PMID- 21873226
TI  - Subcutaneous administration of leptin normalizes fasting plasma glucose in obese
      type 2 diabetic UCD-T2DM rats.
AB  - Leptin has been shown to reduce hyperglycemia in rodent models of type 1
      diabetes. We investigated the effects of leptin administration in University of
      California, Davis, type 2 diabetes mellitus (UCD-T2DM) rats, which develop adult
      onset polygenic obesity and type 2 diabetes. Animals that had been diabetic for 2
      mo were treated with s.c. injections of saline (control) or murine leptin (0.5
      mg/kg) twice daily for 1 mo. Control rats were pair-fed to leptin-treated
      animals. Treatment with leptin normalized fasting plasma glucose and was
      accompanied by lowered HbA1c, plasma glucagon, and triglyceride concentrations
      and expression of hepatic gluconeogenic enzymes compared with vehicle (P < 0.05),
      independent of any effects on body weight and food intake. In addition, leptin
      treated animals exhibited marked improvement of insulin sensitivity and glucose
      homeostasis compared with controls, whereas pancreatic insulin content was 50%
      higher in leptin-treated animals (P < 0.05). These effects coincided with
      activation of leptin and insulin signaling pathways and down-regulation of the
      PKR-like endoplasmic reticulum (ER) kinase/eukaryotic translation inhibition
      factor 2alpha (PERK-eIF2alpha) arm of ER stress in liver, skeletal muscle, and
      adipose tissue as well as increased pro-opiomelanocortin and decreased agouti
      related peptide in the hypothalamus. In contrast, several markers of
      inflammation/immune function were elevated with leptin treatment in the same
      tissues (P < 0.05), suggesting that the leptin-mediated increase of insulin
      sensitivity was not attributable to decreased inflammation. Thus, leptin
      administration improves insulin sensitivity and normalizes fasting plasma glucose
      in diabetic UCD-T2DM rats, independent of energy intake, via peripheral and
      possibly centrally mediated actions, in part by decreasing circulating glucagon
      and ER stress.

PMID- 21873227
TI  - Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation
      Complex (SEC) to RNA polymerase II on chromatin.
AB  - The Super Elongation Complex (SEC), containing transcription elongation
      activators/coactivators P-TEFb, ELL2, AFF4/1, ENL, and AF9, is recruited by HIV-1
      Tat and mixed lineage leukemia (MLL) proteins to activate the expression of HIV-1
      and MLL-target genes, respectively. In the absence of Tat and MLL, however, it is
      unclear how SEC is targeted to RNA polymerase (Pol) II to stimulate elongation in
      general. Furthermore, although ENL and AF9 can bind the H3K79 methyltransferase
      Dot1L, it is unclear whether these bindings are required for SEC-mediated
      transcription. Here, we show that the homologous ENL and AF9 exist in separate
      SECs with similar but nonidentical functions. ENL/AF9 contacts the scaffolding
      protein AFF4 that uses separate domains to recruit different subunits into SEC.
      ENL/AF9 also exists outside SEC when bound to Dot1L, which is found to inhibit
      SEC function. The YEATS domain of ENL/AF9 targets SEC to Pol II on chromatin
      through contacting the human Polymerase-Associated Factor complex (PAFc) complex.
      This finding explains the YEATS domain's dispensability for leukemogenesis when
      ENL/AF9 is translocated to MLL, whose interactions with PAFc and DNA likely
      substitute for the PAFc/chromatin-targeting function of the YEATS domain.

PMID- 21873228
TI  - Control of body size by oxygen supply reveals size-dependent and size-independent
      mechanisms of molting and metamorphosis.
AB  - Body size profoundly affects many aspects of animal biology, including
      metamorphosis, allometry, size-dependent alternative pathways of gene expression,
      and the social and ecological roles of individuals. However, regulation of body
      size is one of the fundamental unsolved problems in developmental biology. The
      control of body size requires a mechanism that assesses size and stops growth
      within a characteristic range of sizes. Under normal growth conditions in Manduca
      sexta, the endocrine cascade that causes the brain to initiate metamorphosis
      starts when the larva reaches a critical weight. Metamorphosis is initiated by a
      size-sensing mechanism, but the nature of this mechanism has remained elusive.
      Here we show that this size-sensing mechanism depends on the limited ability of a
      fixed tracheal system to sustain the oxygen supply to a growing individual. As
      body mass increases, the demand for oxygen also increases, but the fixed tracheal
      system does not allow a corresponding increase in oxygen supply. We show that
      interinstar molting has the same size-related oxygen-dependent mechanism of
      regulation as metamorphosis. We show that low oxygen tension induces molting at
      smaller body size, consistent with the hypothesis that under normal growth
      conditions, body size is regulated by a mechanism that senses oxygen limitation.
      We also found that under poor growth conditions, larvae may never attain the
      critical weight but eventually molt regardless. We show that under these
      conditions, larvae do not use the critical weight mechanism, but instead use a
      size-independent mechanism that is independent of the brain.

PMID- 21873229
TI  - Topology of human apolipoprotein E3 uniquely regulates its diverse biological
      functions.
AB  - Human apolipoprotein E (apoE) is one of the major determinants in lipid
      transport, playing a critical role in atherosclerosis and other diseases. Binding
      to lipid and heparan sulfate proteoglycans (HSPG) induces apoE to adopt active
      conformations for binding to low-density lipoprotein receptor (LDLR) family. ApoE
      also interacts with beta amyloid peptide, manifests critical isoform-specific
      effects on Alzheimer's disease. Despite the importance of apoE in these major
      human diseases, the fundamental questions of how apoE adjusts its structure upon
      binding to regulate its diverse functions remain unsolved. We report the NMR
      structure of apoE3, displaying a unique topology of three structural domains. The
      C-terminal domain presents a large exposed hydrophobic surface that likely
      initiates interactions with lipids, HSPG, and beta amyloid peptides. The unique
      topology precisely regulates apoE tertiary structure to permit only one possible
      conformational adaptation upon binding and provides a double security in
      preventing lipid-free and partially-lipidated apoE from premature binding to apoE
      receptors during receptor biogenesis. This topology further ensures the optimal
      receptor-binding activity by the fully lipidated apoE during lipoprotein
      transport in circulation and in the brain. These findings provide a structural
      framework for understanding the structural basis of the diverse functions of this
      important protein in human diseases.

PMID- 21873230
TI  - Stability of plant immune-receptor resistance proteins is controlled by SKP1
      CULLIN1-F-box (SCF)-mediated protein degradation.
AB  - The nucleotide-binding domain and leucine-rich repeats containing proteins (NLRs)
      serve as immune receptors in both plants and animals. Overaccumulation of NLRs
      often leads to autoimmune responses, suggesting that the levels of these immune
      receptors must be tightly controlled. However, the mechanism by which NLR protein
      levels are regulated is unknown. Here we report that the F-box protein CPR1
      controls the stability of plant NLR resistance proteins. Loss-of-function
      mutations in CPR1 lead to higher accumulation of the NLR proteins SNC1 and RPS2,
      as well as autoactivation of immune responses. The autoimmune responses in cpr1
      mutant plants can be largely suppressed by knocking out SNC1. Furthermore, CPR1
      interacts with SNC1 and RPS2 in vivo, and overexpressing CPR1 results in reduced
      accumulation of SNC1 and RPS2, as well as suppression of immunity mediated by
      these two NLR proteins. Our data suggest that SKP1-CULLIN1-F-box (SCF) complex
      mediated stability control of plant NLR proteins plays an important role in
      regulating their protein levels and preventing autoimmunity.

PMID- 21873231
TI  - Conservation of the C-type lectin fold for massive sequence variation in a
      Treponema diversity-generating retroelement.
AB  - Anticipatory ligand binding through massive protein sequence variation is rare in
      biological systems, having been observed only in the vertebrate adaptive immune
      response and in a phage diversity-generating retroelement (DGR). Earlier work has
      demonstrated that the prototypical DGR variable protein, major tropism
      determinant (Mtd), meets the demands of anticipatory ligand binding by novel
      means through the C-type lectin (CLec) fold. However, because of the low sequence
      identity among DGR variable proteins, it has remained unclear whether the CLec
      fold is a general solution for DGRs. We have addressed this problem by
      determining the structure of a second DGR variable protein, TvpA, from the
      pathogenic oral spirochete Treponema denticola. Despite its weak sequence
      identity to Mtd (~16%), TvpA was found to also have a CLec fold, with predicted
      variable residues exposed in a ligand-binding site. However, this site in TvpA
      was markedly more variable than the one in Mtd, reflecting the unprecedented
      approximate 10(20) potential variability of TvpA. In addition, similarity between
      TvpA and Mtd with formylglycine-generating enzymes was detected. These results
      provide strong evidence for the conservation of the formylglycine-generating
      enzyme-type CLec fold among DGRs as a means of accommodating massive sequence
      variation.

PMID- 21873232
TI  - Microbe domestication and the identification of the wild genetic stock of lager
      brewing yeast.
AB  - Domestication of plants and animals promoted humanity's transition from nomadic
      to sedentary lifestyles, demographic expansion, and the emergence of
      civilizations. In contrast to the well-documented successes of crop and livestock
      breeding, processes of microbe domestication remain obscure, despite the
      importance of microbes to the production of food, beverages, and biofuels. Lager
      beer, first brewed in the 15th century, employs an allotetraploid hybrid yeast,
      Saccharomyces pastorianus (syn. Saccharomyces carlsbergensis), a domesticated
      species created by the fusion of a Saccharomyces cerevisiae ale-yeast with an
      unknown cryotolerant Saccharomyces species. We report the isolation of that
      species and designate it Saccharomyces eubayanus sp. nov. because of its
      resemblance to Saccharomyces bayanus (a complex hybrid of S. eubayanus,
      Saccharomyces uvarum, and S. cerevisiae found only in the brewing environment).
      Individuals from populations of S. eubayanus and its sister species, S. uvarum,
      exist in apparent sympatry in Nothofagus (Southern beech) forests in Patagonia,
      but are isolated genetically through intrinsic postzygotic barriers, and
      ecologically through host-preference. The draft genome sequence of S. eubayanus
      is 99.5% identical to the non-S. cerevisiae portion of the S. pastorianus genome
      sequence and suggests specific changes in sugar and sulfite metabolism that were
      crucial for domestication in the lager-brewing environment. This study shows that
      combining microbial ecology with comparative genomics facilitates the discovery
      and preservation of wild genetic stocks of domesticated microbes to trace their
      history, identify genetic changes, and suggest paths to further industrial
      improvement.

PMID- 21873233
TI  - Different telomere-length dynamics at the inner cell mass versus established
      embryonic stem (ES) cells.
AB  - Murine embryonic stem (ES) cells have unusually long telomeres, much longer than
      those in embryonic tissues. Here we address whether hyper-long telomeres are a
      natural property of pluripotent stem cells, such as those present at the
      blastocyst inner cell mass (ICM), or whether it is a characteristic acquired by
      the in vitro expansion of ES cells. We find that ICM cells undergo telomere
      elongation during the in vitro derivation of ES-cell lines. In vivo analysis
      shows that the hyper-long telomeres of morula-injected ES cells remain hyper-long
      at the blastocyst stage and longer than telomeres of the blastocyst ICM. Telomere
      lengthening during derivation of ES-cell lines is concomitant with a decrease in
      heterochromatic marks at telomeres. We also found increased levels of the
      telomere repeat binding factor 1 (TRF1) telomere-capping protein in cultured ICM
      cells before telomere elongation occurs, coinciding with expression of
      pluripotency markers. These results suggest that high TRF1 levels are present in
      pluripotent cells, most likely to ensure proficient capping of the newly
      synthesized telomeres. These results highlight a previously unnoticed difference
      between ICM cells at the blastocyst and ES cells, and suggest that abnormally
      long telomeres in ES cells are likely to result from continuous telomere
      lengthening of proliferating ICM cells locked at an epigenetic state associated
      to pluripotency.

PMID- 21873234
TI  - Basic leucine zipper transcription factor, ATF-like (BATF) regulates
      epigenetically and energetically effector CD8 T-cell differentiation via Sirt1
      expression.
AB  - CD8 T cells play a critical role in protection against viral infections. During
      effector differentiation, CD8 T cells dramatically change chromatin structure and
      cellular metabolism, but how energy production increases in response to these
      epigenetic changes is unknown. We found that loss of basic leucine zipper
      transcription factor, ATF-like (BATF) inhibited effector CD8 T-cell
      differentiation. At the late effector stage, BATF was induced by IL-12 and
      required for IL-12-mediated histone acetylation and survival of effector T cells.
      BATF, together with c-Jun, transcriptionally inhibited expression of the
      nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase Sirt1, resulting
      in increased histone acetylation of the T-bet locus and increased cellular
      NAD(+), which increased ATP production. In turn, high levels of T-bet expression
      and ATP production promoted effector differentiation and cell survival. These
      results suggest that BATF promotes effector CD8 T-cell differentiation by
      regulating both epigenetic remodeling and energy metabolism through Sirt1
      expression.

PMID- 21873235
TI  - Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in
      lymphocytes and lymphoma cell lines.
AB  - The protease activity of the paracaspase Malt1 contributes to antigen receptor
      mediated lymphocyte activation and lymphomagenesis. Malt1 activity is required
      for optimal NF-kappaB activation, but little is known about the responsible
      substrate(s). Here we report that Malt1 cleaved the NF-kappaB family member RelB
      after Arg-85. RelB cleavage induced its proteasomal degradation and specifically
      controlled DNA binding of RelA- or c-Rel-containing NF-kappaB complexes.
      Overexpression of RelB inhibited expression of canonical NF-kappaB target genes
      and led to impaired survival of diffuse large B-cell lymphoma cell lines
      characterized by constitutive Malt1 activity. These findings identify a central
      role for Malt1-dependent RelB cleavage in canonical NF-kappaB activation and
      thereby provide a rationale for the targeting of Malt1 in immunomodulation and
      cancer treatment.

PMID- 21873237
TI  - Relationship between topological order and glass forming ability in densely
      packed enstatite and forsterite composition glasses.
AB  - The atomic structures of magnesium silicate melts are key to understanding
      processes related to the evolution of the Earth's mantle and represent precursors
      to the formation of most igneous rocks. Magnesium silicate compositions also
      represent a major component of many glass ceramics, and depending on their
      composition can span the entire fragility range of glass formation. The silica
      rich enstatite (MgSiO(3)) composition is a good glass former, whereas the
      forsterite (Mg(2)SiO(4)) composition is at the limit of glass formation. Here,
      the structure of MgSiO(3) and Mg(2)SiO(4) composition glasses obtained from
      levitated liquids have been modeled using Reverse Monte Carlo fits to diffraction
      data and by density functional theory. A ring statistics analysis suggests that
      the lower glass forming ability of the Mg(2)SiO(4) glass is associated with a
      topologically ordered and very narrow ring distribution. The MgO(x) polyhedra
      have a variety of irregular shapes in MgSiO(3) and Mg(2)SiO(4) glasses and a
      cavity analysis demonstrates that both glasses have almost no free volume due to
      a large contribution from edge sharing of MgO(x)-MgO(x) polyhedra. It is found
      that while the atomic volume of Mg cations in the glasses increases compared to
      that of the crystalline phases, the number of Mg-O contacts is reduced, although
      the effective chemical interaction of Mg(2+) remains similar. This unusual
      structure-property relation of Mg(2)SiO(4) glass demonstrates that by using
      containerless processing it may be possible to synthesize new families of dense
      glasses and glass ceramics with zero porosity.

PMID- 21873236
TI  - Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular
      basis for signal transduction and disease protection.
AB  - Initiation of the innate immune response requires agonist recognition by pathogen
      recognition receptors such as the Toll-like receptors (TLRs). Toll/interleukin-1
      receptor (TIR) domain-containing adaptors are critical in orchestrating the
      signal transduction pathways after TLR and interleukin-1 receptor activation.
      Myeloid differentiation primary response gene 88 (MyD88) adaptor-like (MAL)/TIR
      domain-containing adaptor protein (TIRAP) is involved in bridging MyD88 to TLR2
      and TLR4 in response to bacterial infection. Genetic studies have associated a
      number of unique single-nucleotide polymorphisms in MAL with protection against
      invasive microbial infection, but a molecular understanding has been hampered by
      a lack of structural information. The present study describes the crystal
      structure of MAL TIR domain. Significant structural differences exist in the
      overall fold of MAL compared with other TIR domain structures: A sequence motif
      comprising a beta-strand in other TIR domains instead corresponds to a long loop,
      placing the functionally important "BB loop" proline motif in a unique surface
      position in MAL. The structure suggests possible dimerization and MyD88
      interacting interfaces, and we confirm the key interface residues by
      coimmunoprecipitation using site-directed mutants. Jointly, our results provide a
      molecular and structural basis for the role of MAL in TLR signaling and disease
      protection.

PMID- 21873238
TI  - The RND-family transporter, HpnN, is required for hopanoid localization to the
      outer membrane of Rhodopseudomonas palustris TIE-1.
AB  - Rhodopseudomonas palustris TIE-1 is a gram-negative bacterium that produces
      structurally diverse hopanoid lipids that are similar to eukaryotic steroids. Its
      genome encodes several homologues to proteins involved in eukaryotic steroid
      trafficking. In this study, we explored the possibility that two of these
      proteins are involved in intracellular hopanoid transport. R. palustris has a
      sophisticated membrane system comprising outer, cytoplasmic, and inner
      cytoplasmic membranes. It also divides asymmetrically, producing a mother and
      swarmer cell. We deleted genes encoding two putative hopanoid transporters that
      belong to the resistance-nodulation-cell division superfamily. Phenotypic
      analyses revealed that one of these putative transporters (HpnN) is essential for
      the movement of hopanoids from the cytoplasmic to the outer membrane, whereas the
      other (Rpal_4267) plays a minor role. C(30) hopanoids, such as diploptene, are
      evenly distributed between mother and swarmer cells, whereas hpnN is required for
      the C(35) hopanoid, bacteriohopanetetrol, to remain localized to the mother cell
      type. Mutant cells lacking HpnN grow like the WT at 30  degrees C but slower at
      38  degrees C. Following cell division at 38  degrees C, the DeltahpnN cells
      remain connected by their cell wall, forming long filaments. This phenotype may
      be attributed to hopanoid mislocalization because a double mutant deficient in
      both hopanoid biosynthesis and transport does not form filaments. However, the
      lack of hopanoids severely compromises cell growth at higher temperatures more
      generally. Because hopanoid mutants only manifest a strong phenotype under
      certain conditions, R. palustris is an attractive model organism in which to
      study their transport and function.

PMID- 21873239
TI  - CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of
      a self-peptide than thymocyte deletion.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are generated during thymocyte
      development and play a crucial role in preventing the immune system from
      attacking the body's cells and tissues. However, how the formation of these cells
      is directed by T-cell receptor (TCR) recognition of self-peptide:major
      histocompatibility complex (MHC) ligands remains poorly understood. We show that
      an agonist self-peptide with which a TCR is strongly reactive can induce a
      combination of thymocyte deletion and CD4(+)CD25(+)Foxp3(+) Treg cell formation
      in vivo. A weakly cross-reactive partial agonist self-peptide could similarly
      induce thymocyte deletion, but failed to induce Treg cell formation. These
      studies indicate that CD4(+)CD25(+)Foxp3(+) Treg cell formation can require
      highly stringent recognition of an agonist self-peptide by developing thymocytes.
      They also refine the "avidity" model of thymocyte selection by demonstrating that
      the quality of the signal mediated by agonist self-peptides, rather than the
      overall intensity of TCR signaling, can be a critical factor in directing
      autoreactive thymocytes to undergo CD4(+)CD25(+)Foxp3(+) Treg cell formation
      and/or deletion during their development.

PMID- 21873240
TI  - Intersection of FOXO- and RUNX1-mediated gene expression programs in single
      breast epithelial cells during morphogenesis and tumor progression.
AB  - Gene expression networks are complicated by the assortment of regulatory factors
      that bind DNA and modulate transcription combinatorially. Single-cell
      measurements can reveal biological mechanisms hidden by population averages, but
      their value has not been fully explored in the context of mRNA regulation. Here,
      we adapted a single-cell expression profiling technique to examine the gene
      expression program downstream of Forkhead box O (FOXO) transcription factors
      during 3D breast epithelial acinar morphogenesis. By analyzing patterns of mRNA
      fluctuations among individual matrix-attached epithelial cells, we found that a
      subset of FOXO target genes was jointly regulated by the transcription factor
      Runt-related transcription factor 1 (RUNX1). Knockdown of RUNX1 causes
      hyperproliferation and abnormal morphogenesis, both of which require normal FOXO
      function. Down-regulating RUNX1 and FOXOs simultaneously causes widespread
      oxidative stress, which arrests proliferation and restores normal acinar
      morphology. In hormone-negative breast cancers lacking human epidermal growth
      factor receptor 2 (HER2) amplification, we find that RUNX1 down-regulation is
      strongly associated with up-regulation of FOXO1, which may be required to support
      growth of RUNX1-negative tumors. The coordinate function of these two tumor
      suppressors may provide a failsafe mechanism that inhibits cancer progression.

PMID- 21873241
TI  - Trial-to-trial variability in the responses of neurons carries information about
      stimulus location in the rat whisker thalamus.
AB  - From the perspective of neural coding, the considerable trial-to-trial
      variability in the responses of neurons to sensory stimuli is puzzling. Trial-to
      trial response variability is typically interpreted in terms of "noise" (i.e., it
      represents either intrinsic noise of the system or information unrelated to the
      stimuli). However, trial-to-trial response variability can be considerably
      different across stimuli, suggesting that it could also provide an important
      contribution to the information conveyed by the neural responses about the
      stimuli. To test this hypothesis, we addressed the problem of discriminating
      stimulus location from the spike-count responses of neurons recorded in the
      ventro-postero-medial (VPM) nucleus of the thalamus in anesthetized rats. Using a
      recently developed information theory approach, we verified that differences
      between stimuli in the trial-to-trial spike-count variability of the responses
      provided an important contribution to the overall information carried by the
      neurons. In addition, we found that the relatively reliable (sub-Poisson) firing
      regime of our VPM neurons was not only more informative, but also more redundant
      between neurons compared with a more variable (Poisson) firing regime with the
      same total number of spikes. The typical increase in trial-to-trial response
      variability from the periphery to the cortex could therefore serve as a strategy
      to reduce redundancy between neurons and promote efficient sparse coding
      distributed in large populations of neurons. Overall, our data suggest that the
      trial-to-trial response variability plays a critical role in establishing the
      trade-off between total information and redundancy between neurons in population
      codes.

PMID- 21873242
TI  - Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated
      by ATP-binding cassette transporter A3.
AB  - Targeting the surface of malignant cells has evolved into a cornerstone in cancer
      therapy, paradigmatically introduced by the success of humoral immunotherapy
      against CD20 in malignant lymphoma. However, tumor cell susceptibility to
      immunochemotherapy varies, with mostly a fatal outcome in cases of resistant
      disease. Here, we show that lymphoma exosomes shield target cells from antibody
      attack and that exosome biogenesis is modulated by the lysosome-related organelle
      associated ATP-binding cassette (ABC) transporter A3 (ABCA3). B-cell lymphoma
      cells released exosomes that carried CD20, bound therapeutic anti-CD20
      antibodies, consumed complement, and protected target cells from antibody attack.
      ABCA3, previously shown to mediate resistance to chemotherapy, was critical for
      the amounts of exosomes released, and both pharmacological blockade and the
      silencing of ABCA3 enhanced susceptibility of target cells to antibody-mediated
      lysis. Mechanisms of cancer cell resistance to drugs and antibodies are linked in
      an ABCA3-dependent pathway of exosome secretion.

PMID- 21873243
TI  - An integrated model of fixational eye movements and microsaccades.
AB  - When we fixate a stationary target, our eyes generate miniature (or fixational)
      eye movements involuntarily. These fixational eye movements are classified as
      slow components (physiological drift, tremor) and microsaccades, which represent
      rapid, small-amplitude movements. Here we propose an integrated mathematical
      model for the generation of slow fixational eye movements and microsaccades. The
      model is based on the concept of self-avoiding random walks in a potential, a
      process driven by a self-generated activation field. The self-avoiding walk
      generates persistent movements on a short timescale, whereas, on a longer
      timescale, the potential produces antipersistent motions that keep the eye close
      to an intended fixation position. We introduce microsaccades as fast movements
      triggered by critical activation values. As a consequence, both slow movements
      and microsaccades follow the same law of motion; i.e., movements are driven by
      the self-generated activation field. Thus, the model contributes a unified
      explanation of why it has been a long-standing problem to separate slow movements
      and microsaccades with respect to their motion-generating principles. We conclude
      that the concept of a self-avoiding random walk captures fundamental properties
      of fixational eye movements and provides a coherent theoretical framework for two
      physiologically distinct movement types.

PMID- 21873244
TI  - In situ molecular NMR picture of bioavailable calcium stabilized as amorphous
      CaCO3 biomineral in crayfish gastroliths.
AB  - Bioavailable calcium is maintained by some crustaceans, in particular freshwater
      crayfish, by stabilizing amorphous calcium carbonate (ACC) within reservoir
      organs--gastroliths, readily providing the Ca(2+) needed to build a new
      exoskeleton. Despite the key scientific and biomedical importance of the in situ
      molecular-level picture of biogenic ACC and its stabilization in a bioavailable
      form, its description has eluded efforts to date. Herein, using multinuclear NMR,
      we accomplish in situ molecular-level characterization of ACC within intact
      gastroliths of the crayfish Cherax quadricarinatus. In addition to the known
      CaCO(3), chitin scaffold and inorganic phosphate (Pi), we identify within the
      gastrolith two primary metabolites, citrate and phosphoenolpyruvate (PEP) and
      quantify their abundance by applying solution NMR techniques to the gastrolith
      "soluble matrix." The long-standing question on the physico-chemical state of ACC
      stabilizing, P-bearing moieties within the gastrolith is answered directly by the
      application of solid state rotational-echo double-resonance (REDOR) and
      transferred-echo double-resonance (TEDOR) NMR to the intact gastroliths: Pi and
      PEP are found molecularly dispersed throughout the ACC as a solid solution.
      Citrate carboxylates are found < 5 A from a phosphate (intermolecular CP
      distance), an interaction that must be mediated by Ca(2+). The high abundance and
      extensive interactions of these molecules with the ACC matrix identify them as
      the central constituents stabilizing the bioavailable form of calcium. This study
      further emphasizes that it is imperative to characterize the intact biogenic
      CaCO(3). Solid state NMR spectroscopy is shown to be a robust and accessible
      means of determining composition, internal structure, and molecular functionality
      in situ.

PMID- 21873245
TI  - Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for
      PET imaging.
AB  - Hypoxia has been shown to be an important microenvironmental parameter
      influencing tumor progression and treatment efficacy. Patient guidance for
      hypoxia-targeted therapy requires evaluation of tumor oxygenation, preferably in
      a noninvasive manner. The aim of this study was to evaluate and validate the
      uptake of [(18)F]HX4, a novel developed hypoxia marker for PET imaging. A
      heterogeneous accumulation of [(18)F]HX4 was found within rat rhabdomyosarcoma
      tumors that was significantly (P < 0.0001) higher compared with the surrounding
      tissues, with temporal increasing tumor-to-blood ratios reaching a plateau of
      7.638 +/- 0.926 and optimal imaging properties 4 h after injection. [(18)F]HX4
      retention in normal tissues was found to be short-lived, homogeneous and
      characterized by a fast progressive temporal clearance. Heterogeneity in
      [(18)F]HX4 tumor uptake was analyzed based on 16 regions within the tumor
      according to the different orthogonal planes at the largest diameter. Validation
      of heterogeneous [(18)F]HX4 tumor uptake was shown by a strong and significant
      relationship (r = 0.722; P < 0.0001) with the hypoxic fraction as calculated by
      the percentage pimonidazole-positive pixels. Furthermore, a causal relationship
      with tumor oxygenation was established, because combination treatment of
      nicotinamide and carbogen resulted in a 40% reduction (P < 0.001) in [(18)F]HX4
      tumor accumulation whereas treatment with 7% oxygen breathing resulted in a 30%
      increased uptake (P < 0.05). [(18)F]HX4 is therefore a promising candidate for
      noninvasive detection and evaluation of tumor hypoxia at a macroscopic level.

PMID- 21873246
TI  - Effects of parasites from salmon farms on productivity of wild salmon.
AB  - The ecological risks of salmon aquaculture have motivated changes to management
      and policy designed to protect wild salmon populations and habitats in several
      countries. In Canada, much attention has focused on outbreaks of parasitic
      copepods, sea lice (Lepeophtheirus salmonis), on farmed and wild salmon in the
      Broughton Archipelago, British Columbia. Several recent studies have reached
      contradictory conclusions on whether the spread of lice from salmon farms affects
      the productivity of sympatric wild salmon populations. We analyzed recently
      available sea lice data on farms and spawner-recruit data for pink (Oncorhynchus
      gorbuscha) and coho (Oncorhynchus kisutch) salmon populations in the Broughton
      Archipelago and nearby regions where farms are not present. Our results show that
      sea lice abundance on farms is negatively associated with productivity of both
      pink and coho salmon in the Broughton Archipelago. These results reconcile the
      contradictory findings of previous studies and suggest that management and policy
      measures designed to protect wild salmon from sea lice should yield conservation
      and fishery benefits.

PMID- 21873247
TI  - Spatiotemporal regulation of chemical reactions by active cytoskeletal
      remodeling.
AB  - Efficient and reproducible construction of signaling and sorting complexes, both
      on the surface and within the living cell, is contingent on local regulation of
      biochemical reactions by the cellular milieu. We propose that in many cases this
      spatiotemporal regulation can be mediated by interaction with components of the
      dynamic cytoskeleton. We show how the interplay between active contractility and
      remodeling of the cytoskeleton can result in transient focusing of passive
      molecules to form clusters, leading to a dramatic increase in the reaction
      efficiency and output levels. The dynamic cytoskeletal elements that drive
      focusing behave as quasienzymes catalyzing the chemical reaction. These ideas are
      directly applicable to the cortical actin-dependent clustering of cell surface
      proteins such as lipid-tethered GPI-anchored proteins, Ras proteins, as well as
      many proteins that have domains that confer the ability to interact with the
      actin cytoskeleton. In general such cytoskeletal driven clustering of proteins
      could be a cellular mechanism to spatiotemporally regulate and amplify local
      chemical reaction rates in a variety of contexts such as signaling,
      transcription, sorting, and endocytosis.

PMID- 21873249
TI  - Three-dimensional structure of a sheet crumpled into a ball.
AB  - When a thin sheet is crushed into a small three-dimensional volume, it invariably
      forms a structure with a low volume fraction but high resistance to further
      compression. Being a far-from-equilibrium process, forced crumpling is not
      necessarily amenable to a statistical description in which the parameters of the
      initially flat sheet and the final confinement fully specify the resulting
      crumpled state. Instead, the internal geometry and mechanical properties of the
      crumpled ball may reflect the history of its preparation. Our X-ray
      microtomography experiments reveal that the internal three-dimensional geometry
      of a crumpled ball is in many respects isotropic and homogeneous. In these
      respects, crumpling recapitulates other classic nonequilibrium problems such as
      turbulence, where a system driven by long-wavelength, low-symmetry, forcing shows
      only rather subtle fingerprints of the forcing mechanism. However, we find local
      nematic ordering of the sheet into parallel stacks. The layering proceeds
      radially inward from the outer surface. The extent of this layering increases
      with the volume fraction, or degree of compression.

PMID- 21873248
TI  - PI3K/Akt signaling requires spatial compartmentalization in plasma membrane
      microdomains.
AB  - Spatial compartmentalization of signaling pathway components generally defines
      the specificity and enhances the efficiency of signal transduction. The
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to be compartmentalized
      within plasma membrane microdomains; however, the underlying mechanisms and
      functional impact of this compartmentalization are not well understood. Here, we
      show that phosphoinositide-dependent kinase 1 is activated in membrane rafts in
      response to growth factors, whereas the negative regulator of the pathway,
      phosphatase and tensin homolog deleted on chromosome 10 (PTEN), is primarily
      localized in nonraft regions. Alteration of this compartmentalization, either by
      genetic targeting or ceramide-induced recruitment of PTEN to rafts, abolishes the
      activity of the entire pathway. These findings reveal critical steps in raft
      mediated PI3K/Akt activation and demonstrate the essential role of membrane
      microdomain compartmentalization in enabling PI3K/Akt signaling. They further
      suggest that dysregulation of this compartmentalization may underlie pathological
      complications such as insulin resistance.

PMID- 21873250
TI  - Global impairment and therapeutic restoration of visual plasticity mechanisms
      after a localized cortical stroke.
AB  - We tested the influence of a photothrombotic lesion in somatosensory cortex on
      plasticity in the mouse visual system and the efficacy of anti-inflammatory
      treatment to rescue compromised learning. To challenge plasticity mechanisms, we
      induced monocular deprivation (MD) in 3-mo-old mice. In control animals, MD
      induced an increase of visual acuity of the open eye and an ocular dominance (OD)
      shift towards this eye. In contrast, after photothrombosis, there was neither an
      enhancement of visual acuity nor an OD-shift. However, OD-plasticity was present
      in the hemisphere contralateral to the lesion. Anti-inflammatory treatment
      restored sensory learning but not OD-plasticity, as did a 2-wk delay between
      photothrombosis and MD. We conclude that (i) both sensory learning and cortical
      plasticity are compromised in the surround of a cortical lesion; (ii) transient
      inflammation is responsible for impaired sensory learning, suggesting anti
      inflammatory treatment as a useful adjuvant therapy to support rehabilitation
      following stroke; and (iii) OD-plasticity cannot be conceptualized solely as a
      local process because nonlocal influences are more important than previously
      assumed.

PMID- 21873251
TI  - The million-year wait for macroevolutionary bursts.
AB  - We lack a comprehensive understanding of evolutionary pattern and process because
      short-term and long-term data have rarely been combined into a single analytical
      framework. Here we test alternative models of phenotypic evolution using a
      dataset of unprecedented size and temporal span (over 8,000 data points). The
      data are body-size measurements taken from historical studies, the fossil record,
      and among-species comparative data representing mammals, squamates, and birds. By
      analyzing this large dataset, we identify stochastic models that can explain
      evolutionary patterns on both short and long timescales and reveal a remarkably
      consistent pattern in the timing of divergence across taxonomic groups. Even
      though rapid, short-term evolution often occurs in intervals shorter than 1 Myr,
      the changes are constrained and do not accumulate over time. Over longer
      intervals (1-360 Myr), this pattern of bounded evolution yields to a pattern of
      increasing divergence with time. The best-fitting model to explain this pattern
      is a model that combines rare but substantial bursts of phenotypic change with
      bounded fluctuations on shorter timescales. We suggest that these rare bursts
      reflect permanent changes in adaptive zones, whereas the short-term fluctuations
      represent local variations in niche optima due to restricted environmental
      variation within a stable adaptive zone.

PMID- 21873252
TI  - Random partitioning of molecules at cell division.
AB  - Many RNAs, proteins, and organelles are present in such low numbers per cell that
      random segregation of individual copies causes large "partitioning errors" at
      cell division. Even symmetrically dividing cells can then by chance produce
      daughters with very different composition. The size of the errors depends on the
      segregation mechanism: Control systems can reduce low-abundance errors, but the
      segregation process can also be subject to upstream sources of randomness or
      spatial heterogeneities that create large errors despite high abundances. Here we
      mathematically demonstrate how partitioning errors arise for different types of
      segregation mechanisms and how errors can be greatly increased by upstream
      heterogeneity but remarkably hard to avoid through controlled partitioning. We
      also show that seemingly straightforward experiments cannot be straightforwardly
      interpreted because very different mechanisms produce identical fits and present
      an approach to deal with this problem by adding binomial counting noise and
      testing for convexity or concavity in the partitioning error as a function of the
      binomial thinning parameter. The results lay a conceptual groundwork for more
      effective studies of heterogeneity among growing and dividing cells, whether in
      microbes or in differentiating tissues.

PMID- 21873253
TI  - Reduced cathartic bowel preparation for CT colonography: prospective comparison
      of 2-L polyethylene glycol and magnesium citrate.
AB  - PURPOSE: To prospectively compare adequacy of colonic cleansing, adequacy of
      solid stool and fluid tagging, and patient acceptance by using reduced-volume, 2
      L polyethylene glycol (PEG) versus magnesium citrate bowel preparations for CT
      colonography. MATERIALS AND METHODS: This study was approved by the institutional
      Committee on Human Research and was compliant with HIPAA; all patients provided
      written consent. In this randomized, investigator-blinded study, 50 patients
      underwent oral preparation with either a 2-L PEG or a magnesium citrate solution,
      tagging with oral contrast agents, and subsequent CT colonography and segmentally
      unblinded colonoscopy. The residual stool (score 0 [best] to 3 [worst]) and fluid
      (score 0 [best] to 4 [worst]) burden and tagging adequacy were qualitatively
      assessed. Residual fluid attenuation was recorded as a quantitative measure of
      tagging adequacy. Patients completed a tolerance questionnaire within 2 weeks of
      scanning. Preparations were compared for residual stool and fluid by using
      generalized estimating equations; the Mann-Whitney test was used to compare the
      qualitative tagging score, mean residual fluid attenuation, and adverse effects
      assessed on the patient experience questionnaire. RESULTS: The mean residual
      stool (0.90 of three) and fluid burden (1.05 of four) scores for PEG were similar
      to those for magnesium citrate (0.96 [P = .58] and 0.98 [P = .48], respectively).
      However, the mean fecal and fluid tagging scores were significantly better for
      PEG (0.48 and 0.28, respectively) than for magnesium citrate (1.52 [P < .01] and
      1.28 [P < .01], respectively). Mean residual fluid attenuation was higher for PEG
      (765 HU) than for magnesium citrate (443 HU, P = .01), and mean interpretation
      time was shorter for PEG (14.8 minutes) than for magnesium citrate (18.0 minutes,
      P = .04). Tolerance ratings were not significantly different between
      preparations. CONCLUSION: Reduced-volume PEG and magnesium citrate bowel
      preparations demonstrated adequate cleansing effectiveness for CT colonography,
      with better tagging and shorter interpretation time observed in the PEG group.
      Adequate polyp detection was maintained but requires further validation because
      of the small number of clinically important polyps.

PMID- 21873254
TI  - Stable angina pectoris: head-to-head comparison of prognostic value of cardiac CT
      and exercise testing.
AB  - PURPOSE: To determine and compare the prognostic value of cardiac computed
      tomographic (CT) angiography, coronary calcium scoring, and exercise
      electrocardiography (ECG) in patients with chest pain who are suspected of having
      coronary artery disease (CAD). MATERIALS AND METHODS: This study complied with
      the Declaration of Helsinki, and the local ethics committee approved the study.
      Patients (n = 471) without known CAD underwent exercise ECG and dual-source CT at
      a rapid assessment outpatient chest pain clinic. Coronary calcification and the
      presence of 50% or greater coronary stenosis (in one or more vessels) were
      assessed with CT. Exercise ECG results were classified as normal, ischemic, or
      nondiagnostic. The primary outcome was a major adverse cardiac event (MACE),
      defined as cardiac death, nonfatal myocardial infarction, or unstable angina
      requiring hospitalization and revascularization beyond 6 months. Univariable and
      multivariable Cox regression analysis was used to determine the prognostic
      values, while clinical impact was assessed with the net reclassification
      improvement metric. RESULTS: Follow-up was completed for 424 (90%) patients; the
      mean duration of follow-up was 2.6 years. A total of 44 MACEs occurred in 30
      patients. Four of the MACEs were cardiac deaths and six were nonfatal myocardial
      infarctions. The presence of coronary calcification (hazard ratio [HR], 8.22 [95%
      confidence interval {CI}: 1.96, 34.51]), obstructive CAD (HR, 6.22 [95% CI: 2.77,
      13.99]), and nondiagnostic stress test results (HR, 3.00 [95% CI: 1.26, 7.14])
      were univariable predictors of MACEs. In the multivariable model, CT angiography
      findings (HR, 5.0 [95% CI: 1.7, 14.5]) and nondiagnostic exercise ECG results
      (HR, 2.9 [95% CI: 1.2, 7.0]) remained independent predictors of MACEs. CT
      angiography findings showed incremental value beyond clinical predictors and
      stress testing (global chi(2), 37.7 vs 13.7; P < .001), whereas coronary calcium
      scores did not have further incremental value (global chi(2), 38.2 vs 37.7; P =
      .40). CONCLUSION: CT angiography findings are a strong predictor of future
      adverse events, showing incremental value over clinical predictors, stress
      testing, and coronary calcium scores. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110744/-/DC1.

PMID- 21873256
TI  - Reticular infiltrations alone without mass in the mesentery and omentum
      identified at contrast-enhanced CT: efficacy of US-guided percutaneous core
      biopsy.
AB  - PURPOSE: To evaluate the diagnostic efficacy of ultrasonographically (US) guided
      percutaneous core biopsy of reticular infiltrations alone without mass in the
      mesentery and omentum at contrast material-enhanced abdominal computed tomography
      (CT). MATERIALS AND METHODS: This study was approved by the institutional review
      board, and the need for obtaining signed informed consent was waived for this
      retrospective analysis. From March 2004 to May 2009, 45 patients (mean age, 52.3
      years; age range, 21-89 years) with reticular infiltrations alone without mass in
      the mesentery and omentum at contrast-enhanced abdominal CT underwent US-guided
      percutaneous core biopsy. Twenty-one men and 24 women were included. The area
      with the severest infiltrations at CT was targeted during real-time US-guided
      percutaneous biopsy. Biopsy results were compared with the final results of
      surgery or follow-up. The diagnostic accuracy of US-guided percutaneous biopsy
      was then calculated. RESULTS: One patient had an insufficient biopsy specimen.
      Among the 44 patients with sufficient biopsy specimens, 17 patients had
      malignancy, 12 had tuberculosis, and 15 had nonspecific inflammation. All 29
      patients with malignancy and tuberculosis at biopsy had that confirmed with
      surgery or follow-up results. Two of 15 patients with nonspecific inflammation at
      percutaneous biopsy were confirmed as having malignancy at surgery and four as
      having tuberculosis after improvement with empirical antituberculosis therapy.
      The diagnostic accuracy of US-guided percutaneous biopsy of reticular
      infiltrations in the mesentery and omentum was 84%; the sensitivity and
      specificity was, respectively, 89% and 100% for malignancy, 75% and 100% for
      tuberculosis, and 90% and 83% for nonspecific inflammation. CONCLUSION: US-guided
      percutaneous core biopsy is a feasible diagnostic method with high specificity
      for confirmative diagnosis of reticular infiltrations alone in the mesentery and
      omentum at contrast-enhanced CT.

PMID- 21873257
TI  - Transcapsular arterial neovascularization after liver transplantation in
      pediatric patients indicates transplant failure.
AB  - PURPOSE: To identify transcapsular arterial neovascularization with Doppler
      ultrasonography (US) in pediatric patients after liver transplantation and to
      assess the frequency of the finding, its underlying causes, and its relevance in
      terms of clinical outcome. MATERIALS AND METHODS: The study was approved by the
      local ethics committee, with waived informed consent. All pediatric patients who
      underwent liver transplantation between January 2000 and December 2003 were
      retrospectively evaluated. Patients were followed up until June 2008, by using a
      predefined US protocol with prospective documentation. Of 182 consecutive liver
      transplantations performed in 162 patients (mean age, 4.5 years; range, 0.1-18.4
      years) in this period, 25 patients with a total of 27 liver transplantations
      underwent US examinations conducted by multiple investigators and were primarily
      excluded. Student t tests and chi(2) tests were performed where appropriate. The
      Tarone-Ware test was used to compare transplant survival times. RESULTS:
      Transcapsular arterial neovascularization was noticed in 13 of 137 patients
      (9.5%) and in 13 of 155 liver transplants (8.4%). The mean time until arterial
      neovessels appeared was 157 days after liver transplantation (median, 97 days;
      range, 19-477 days). Arterial neovascularization was associated with pronounced
      transplant malperfusion and inflammatory changes (P < .001). Patients with
      transcapsular arterial neovascularization had a significantly shorter mean
      transplant survival time (1426.4 days +/- 244.5 [standard error], with 95%
      confidence interval: 947.23, 1905.23, vs 2526.4 days +/- 92.1, with 95%
      confidence interval: 2345.84, 2706.97; P = .008) and a higher retransplantation
      rate (53.8% vs 19.7%, P = .009). CONCLUSION: Transcapsular arterial
      neovascularization, detected with color Doppler US, occurred in 9.5% (13 of 137)
      of pediatric patients and 8.4% (13 of 155) of liver transplants and was
      associated with underlying malperfusion and inflammation. The diagnosis of
      transcapsular arterial neovascularization was associated with reduced graft
      survival times and a high retransplantation rate. The negative prognostic value
      of the sign may assist in a strategy of organ allocation.

PMID- 21873255
TI  - Prostate cancer: prediction of biochemical failure after external-beam radiation
      therapy--Kattan nomogram and endorectal MR imaging estimation of tumor volume.
AB  - PURPOSE: To determine whether magnetic resonance (MR) imaging and MR
      spectroscopic imaging findings can improve predictions made with the Kattan
      nomogram for radiation therapy. MATERIALS AND METHODS: The institutional review
      board approved this retrospective HIPAA-compliant study. Ninety-nine men who
      underwent endorectal MR and MR spectroscopy before external-beam radiation
      therapy for prostate cancer (January 1998 to June 2007) were included. Linear
      predictors were calculated with input variables from the study sample and the
      Kattan original coefficients. The linear predictor is a single weighted value
      that combines information of all predictor variables in a model, where the weight
      of each value is its association with the outcome. Two radiologists independently
      reviewed all MR images to determine extent of disease; a third independent reader
      resolved discrepancies. Biochemical failure was defined as a serum prostate
      specific antigen level of 2 ng/mL (2 MUg/L) or more above nadir. Cox proportional
      hazard models were used to determine the probabilities of treatment failure
      (biochemical failure) in 5 years. One model included only the Kattan nomogram
      data; the other also incorporated imaging findings. The discrimination
      performance of all models was determined with receiver operating characteristics
      (ROC) curve analyses. These analyses were followed by an assessment of net risk
      reclassification. RESULTS: The areas under the ROC curve for the Kattan nomogram
      and the model incorporating MR imaging findings were 61.1% (95% confidence
      interval: 58.1%, 64.0%) and 78.0% (95% confidence interval: 75.7%, 80.4%),
      respectively. Comparison of performance showed that the model with imaging
      findings performed significantly better than did the model with clinical
      variables alone (P < .001). Overall, the addition of imaging findings led to an
      improvement in risk classification of about 28%, ranging from approximately a
      minimum of 16% to a maximum of 39%, depending on the risk change considered
      important. CONCLUSION: MR imaging data improve the prediction of biochemical
      failure with the Kattan nomogram after external-beam radiation therapy for
      prostate cancer. The number needed to image to improve the prediction of
      biochemical failure in one patient ranged from three to six.

PMID- 21873259
TI  - Ontogenetic contingency of tolerance mechanisms in response to apical damage.
AB  - BACKGROUND AND AIMS: Plants are able to tolerate tissue loss through vigorous
      branching which is often triggered by release from apical dominance and
      activation of lateral meristems. However, damage-induced branching might not be a
      mere physiological outcome of released apical dominance, but an adaptive response
      to environmental signals, such as damage timing and intensity. Here, branching
      responses to both factors were examined in the annual plant Medicago truncatula.
      METHODS: Branching patterns and allocation to reproductive traits were examined
      in response to variable clipping intensities and timings in M. truncatula plants
      from two populations that vary in the onset of reproduction. Phenotypic selection
      analysis was used to evaluate the strength and direction of selection on
      branching under the damage treatments. KEY RESULTS: Plants of both populations
      exhibited an ontogenetic shift in tolerance mechanisms: while early damage
      induced greater meristem activation, late damage elicited investment in late
      determined traits, including mean pod and seed biomass, and supported greater
      germination rates. Severe damage mostly elicited simultaneous development of
      multiple-order lateral branches, but this response was limited to early damage.
      Selection analyses revealed positive directional selection on branching in plants
      under early- compared with late- or no-damage treatments. CONCLUSIONS: The
      results demonstrate that damage-induced meristem activation is an adaptive
      response that could be modified according to the plant's developmental stage,
      severity of tissue loss and their interaction, stressing the importance of
      considering these effects when studying plastic responses to apical damage.

PMID- 21873260
TI  - Impaired mitochondrial biogenesis, defective axonal transport of mitochondria,
      abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of
      Alzheimer's disease.
AB  - Increasing evidence suggests that the accumulation of amyloid beta (Abeta) in
      synapses and synaptic mitochondria causes synaptic mitochondrial failure and
      synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was
      to better understand the effects of Abeta in mitochondrial activity and synaptic
      alterations in neurons from a mouse model of AD. Using primary neurons from a
      well-characterized Abeta precursor protein transgenic (AbetaPP) mouse model
      (Tg2576 mouse line), for the first time, we studied mitochondrial activity,
      including axonal transport of mitochondria, mitochondrial dynamics, morphology
      and function. Further, we also studied the nature of Abeta-induced synaptic
      alterations, and cell death in primary neurons from Tg2576 mice, and we sought to
      determine whether the mitochondria-targeted antioxidant SS31 could mitigate the
      effects of oligomeric Abeta. We found significantly decreased anterograde
      mitochondrial movement, increased mitochondrial fission and decreased fusion,
      abnormal mitochondrial and synaptic proteins and defective mitochondrial function
      in primary neurons from AbetaPP mice compared with wild-type (WT) neurons.
      Transmission electron microscopy revealed a large number of small mitochondria
      and structurally damaged mitochondria, with broken cristae in AbetaPP primary
      neurons. We also found an increased accumulation of oligomeric Abeta and
      increased apoptotic neuronal death in the primary neurons from the AbetaPP mice
      relative to the WT neurons. Our results revealed an accumulation of intraneuronal
      oligomeric Abeta, leading to mitochondrial and synaptic deficiencies, and
      ultimately causing neurodegeneration in AbetaPP cultures. However, we found that
      the mitochondria-targeted antioxidant SS31 restored mitochondrial transport and
      synaptic viability, and decreased the percentage of defective mitochondria,
      indicating that SS31 protects mitochondria and synapses from Abeta toxicity.

PMID- 21873262
TI  - Effects of advanced selection methods on sperm quality and ART outcome: a
      systematic review.
AB  - BACKGROUND: Current routine semen preparation techniques do not inclusively
      target all intrinsic sperm characteristics that may impact the fertilization
      potential. In order to address these characteristics, several methods have been
      recently developed and applied to sperm selection. The objective of this study
      was to systematically review the literature describing these advanced sperm
      selection methods focusing on their anticipated benefits on sperm quality and
      assisted reproductive technique (ART) outcome. METHODS: Systematic literature
      review was conducted by means of a Medline literature search. Sperm quality
      parameters assessed included: motility, morphology, viability, DNA integrity,
      apoptosis and maturity. ART outcomes assessed included: fertilization, embryo
      quality, pregnancy, abortion and live birth rates. RESULTS: A total of 44 studies
      were identified describing four advanced sperm selection methods based on: (i)
      surface charge (electrophoresis and zeta potential), (ii) apoptosis (magnetic
      cell sorting and glass wool), (iii) membrane maturity (hyaluronic acid binding)
      and (iv) ultramorphology (high magnification). Selection of high-quality sperm
      including improvements in DNA integrity, resulted from the application of these
      methods. Fertilization and pregnancy rates showed improvement following some of
      the advanced sperm selection techniques. CONCLUSIONS: While some of the advanced
      sperm selection methods are of value in specific clinical ART settings, others
      are in need of further evaluation. More clinical studies on safety and efficacy
      are needed before the implementation of advanced sperm selection methods could be
      universally recommended in ART.

PMID- 21873261
TI  - Genetic risk prediction in complex disease.
AB  - Attempting to classify patients into high or low risk for disease onset or
      outcomes is one of the cornerstones of epidemiology. For some (but by no means
      all) diseases, clinically usable risk prediction can be performed using classical
      risk factors such as body mass index, lipid levels, smoking status, family
      history and, under certain circumstances, genetics (e.g. BRCA1/2 in breast
      cancer). The advent of genome-wide association studies (GWAS) has led to the
      discovery of common risk loci for the majority of common diseases. These
      discoveries raise the possibility of using these variants for risk prediction in
      a clinical setting. We discuss the different ways in which the predictive
      accuracy of these loci can be measured, and survey the predictive accuracy of
      GWAS variants for 18 common diseases. We show that predictive accuracy from
      genetic models varies greatly across diseases, but that the range is similar to
      that of non-genetic risk-prediction models. We discuss what factors drive
      differences in predictive accuracy, and how much value these predictions add over
      classical predictive tests. We also review the uses and pitfalls of idealized
      models of risk prediction. Finally, we look forward towards possible future
      clinical implementation of genetic risk prediction, and discuss realistic
      expectations for future utility.

PMID- 21873265
TI  - Sleep and fatigue and the relationship to pain, disease activity and quality of
      life in juvenile idiopathic arthritis and juvenile dermatomyositis.
AB  - OBJECTIVES: To determine and compare the prevalence of disturbed sleep in JIA and
      JDM and the relationship of sleep disturbance to pain, function, disease activity
      and medications. METHODS: One hundred fifty-five patients (115 JIA, 40 JDM) were
      randomly sampled and were mailed questionnaires. Sleep disturbance was assessed
      by the sleep self-report (SSR) and the children's sleep habits questionnaire
      (CSHQ). Fatigue, pain and function were assessed by the paediatric quality of
      life inventory (PedsQL) and disease activity by visual analogue scales (VASs).
      Joint counts were self-reported. RESULTS: Eighty-one per cent responded, of whom
      44% reported disturbed sleep (CSHQ > 41); there were no differences between
      disease groups. Poor reported sleep (SSR) was highly correlated with PedsQL
      fatigue (r = 0.56, P < 0.0001). Fatigue was highly negatively correlated with
      quality of life (r = -0.77, P < 0.0001). The worst pain intensity in the last
      week was correlated to sleep disturbance (r = 0.32, P = 0.0005). Fatigue was
      associated with prednisone and DMARD use. CONCLUSIONS: Sleep disturbance and
      fatigue are prevalent among children with different rheumatic diseases. Sleep
      disturbance and fatigue are strongly associated with increased pain and decreased
      quality of life. Strategies aimed at improving sleep and reducing fatigue should
      be studied as possible ways of improving quality of life for children with
      rheumatic illness.

PMID- 21873266
TI  - Vasculitis of the temporal artery in a young woman.

PMID- 21873264
TI  - Tissue and serum markers of inflammation during the follow-up of patients with
      giant-cell arteritis--a prospective longitudinal study.
AB  - OBJECTIVE: To evaluate the association between inflammatory markers and relapse
      in GCA patients longitudinally assessed in a clinical trial of infliximab and
      glucocorticosteroids. METHODS: Forty-four newly diagnosed GCA patients in
      glucocorticosteroid-induced remission were randomized to receive infliximab 5
      mg/kg or placebo plus daily glucocorticosteroids, tapered using a standardized
      schedule. Sera were analysed for inflammatory markers at multiple, pre-defined
      time points. Temporal artery biopsies were performed in four patients before and
      after treatment to analyse changes in inflammatory and vascular remodelling
      marker expression. RESULTS: Thirteen of 44 patients relapsed. Similar proportions
      of relapsed patients were present in both treatment arms. ESR, CRP, intercellular
      adhesion molecule (ICAM)-1, TNF-alpha, and IL-12p40 were significantly elevated
      near relapse. In post-treatment biopsies, mRNA expression of pro-inflammatory
      cytokines decreased, while vascular remodelling factors increased relative to
      baseline biopsies. Tissue IL-12p40 and IFN-gamma mRNA remained elevated in
      relapsing vs remitting patients. CONCLUSION: Despite prior findings of high
      concentrations of TNF-alpha in temporal artery biopsies of GCA patients,
      infliximab plus glucocorticosteroids did not result in improved clinical
      outcomes. Increased measures of this biomarker did not provide useful insight
      into the relative importance of TNF-alpha in the pathogenesis of GCA. Gene
      expression analysis in paired temporal artery biopsies pre- and post-treatment
      revealed decreased inflammatory activity and active vascular remodelling
      following treatment. In relapsing patients, increased expression of IFN-gamma and
      IL-12p40 in post-treatment biopsies suggests a role in sustaining disease and
      setting the stage for relapse during treatment withdrawal. TRIAL REGISTRATION:
      ClinicalTrials.gov; http://www.clinicaltrials.gov; NCT00076726.

PMID- 21873267
TI  - (99m)Tc-anti-TNF-alpha scintigraphy in RA: a comparison pilot study with MRI and
      clinical examination.
AB  - OBJECTIVE: To compare the use of radiolabelled human monoclonal anti-TNF-alpha
      scintigraphy with clinical examination and MRI of hands and wrists joints in
      patients with active RA. METHODS: Eight patients with active RA, 28-joint DAS
      (DAS-28) >= 3.2 and a healthy volunteer underwent whole body and hand/wrist
      scintigraphy after the administration of anti-human TNF-alpha labelled with
      technetium-99m ((99m)Tc). One hundred and ninety-eight joints were examined.
      Patients were also given clinical examinations in addition to MRI of the hands
      and wrists. RESULTS: Of the 198 joints examined, signs of inflammation were
      detected by MRI in 49 (24.7%) and by scintigraphy in 48 (24.2%) joints, with
      agreement between the two methods in 44 joints. In five joints, MRI was positive
      and scintigraphy negative. In another four joints, scintigraphy was positive and
      MRI negative for signs of inflammation. MRI and scintigraphy were in agreement
      for negative results for 145 joints. The sensitivity and specificity of
      scintigraphy was 89.8 and 97.3%, respectively. When clinical parameters (presence
      of swelling and tenderness of joints) were compared with the MRI findings, lower
      correlation coefficients were observed (sensitivity of 59.2% and 65.3%,
      respectively). CONCLUSIONS: Scintigraphy using (99m)Tc-anti-TNF-alpha showed high
      correlation with the presence of inflammatory signs detected by MRI in the hands
      and wrists of patients with active RA, and demonstrated a greater sensitivity
      than clinical examination. These results can assist in better understanding of
      anti-cytokine therapy and support the achievement of evidence-based biologic
      therapy.

PMID- 21873268
TI  - Negotiating targets with patients: choice of target in relation to occupational
      state.
AB  - OBJECTIVES: Following the recent National Institute for Health and Clinical
      Excellence guidance on the management of RA, we were interested to see if we
      could negotiate targets for treatment with patients in routine clinics, how they
      would express this and whether staying at work would be a target. METHODS: One
      hundred RA patients were recruited. They were consecutive within clinics, but not
      all clinics were used. They were asked their understanding of the DAS score and a
      target for treatment negotiated. Any impact of the RA on their paid employment
      was then explored. RESULTS: Four participants were unable to specify a target for
      their RA. Negotiated targets were expressed as restricted activities and either
      as maintaining an activity (70) if the disease was stable, or regaining an
      activity (26) if the treatment was being increased. Targets were walking a
      distance for 50% of patients; leisure activities for 18%; domestic activities for
      17%; work for 14% and personal care for 2%. For the 21 participants currently
      working, maintaining work was the target for 12, with 1 wishing to regain lost
      hours. No patient currently not working expressed returning to work as a target.
      There were some differences in targets between men and women. CONCLUSIONS:
      Patients are able to negotiate a target for their treatment, expressed as
      maintaining or regaining a physical activity. Work ceases to be a target once it
      is lost. Therefore, preventing loss of occupation is likely to be more effective
      than trying to regain it.

PMID- 21873269
TI  - Interstitial lung disease and ANCA-associated vasculitis: a retrospective
      observational cohort study.
AB  - OBJECTIVES: ANCA-associated vasculitis and interstitial lung disease (ILD) are
      uncommon conditions. The occurrence of both diseases in the same patient is
      increasingly recognized. Our aim was to ascertain the characteristics and
      outcomes of patients with ILD and ANCA-associated vasculitis. METHODS: A
      retrospective observational cohort study was performed. Patients who presented to
      the Hammersmith Hospital, London, with ANCA-associated vasculitis [granulomatosis
      with polyangiitis (Wegener's), microscopic polyangiitis (MPA) or Churg-Strauss
      syndrome] who also had ILD were included. Following hospital discharge, all
      patients were followed up in a multi-disciplinary vasculitis clinic. We recorded
      patient demographics, diagnostic tests, treatment, complications and mortality.
      RESULTS: ILD was observed in 2.7% (n = 14) of our patients with ANCA-associated
      vasculitis (n = 510); all had MPO-ANCA and a clinical diagnosis of MPA, giving a
      prevalence of 7.2% in patients with MPA (n = 194). There was no significant
      difference in survival between patients with MPA and ILD and those with MPA
      alone. CONCLUSION: It is important that physicians are aware of this clinical
      association and the presence of ILD should be considered in all patients with
      ANCA-associated vasculitis, especially those with MPO-ANCA. The possibility that
      patients with ILD may subsequently develop features of systemic vasculitis should
      also be remembered.

PMID- 21873270
TI  - Transgenic zebrafish model to study translational control mediated by upstream
      open reading frame of human chop gene.
AB  - Upstream open reading frame (uORF)-mediated translational inhibition is important
      in controlling key regulatory genes expression. However, understanding the
      underlying molecular mechanism of such uORF-mediated control system in vivo is
      challenging in the absence of an animal model. Therefore, we generated a
      zebrafish transgenic line, termed huORFZ, harboring a construct in which the uORF
      sequence from human CCAAT/enhancer-binding protein homologous protein gene
      (huORF(chop)) is added to the leader of GFP and is driven by a cytomegalovirus
      promoter. The translation of transgenic huORF(chop)-gfp mRNA was absolutely
      inhibited by the huORF(chop) cassette in huORFZ embryos during normal conditions,
      but the downstream GFP was only apparent when the huORFZ embryos were treated
      with endoplasmic reticulum (ER) stresses. Interestingly, the number and location
      of GFP-responsive embryonic cells were dependent on the developmental stage and
      type of ER stresses encountered. These results indicate that the translation of
      the huORF(chop)-tag downstream reporter gene is controlled in the huORFZ line.
      Moreover, using cell sorting and microarray analysis of huORFZ embryos, we
      identified such putative factors as Nrg/ErbB, PI3K and hsp90, which are involved
      in huORF(chop)-mediated translational control under heat-shock stress. Therefore,
      using the huORFZ embryos allows us to study the regulatory network involved in
      human uORF(chop)-mediated translational inhibition.

PMID- 21873271
TI  - Lip and tongue movements during phonetic sequences: analysis and definition of
      normal values.
AB  - Precise knowledge of lip and tongue movements is limited. Conventional
      investigative methods do not allow for their precise representation and analysis.
      In the present study, electromagnetic articulography (EMA) was used to define
      normal values for lip movements based on consonant-vowel-consonant (CVC)
      sequences and for tongue movements based on vowel-consonant-vowel (VCV)
      sequences. The study population included 25 volunteers (11 males and 14 females)
      with a median age of 26 (23 to 29) years. An EMA unit was used to conduct the
      measurements. For this purpose, the volunteers repeated a number of VCV and CVC
      text sequences 10 times each during two different body positions (upright and
      relaxed). Statistical analysis (including Bland and Altman's measurement error,
      non-parametric Wilcoxon rank score testing, and analysis of variance) of distance
      and time variables resulted in a small measurement error. There was no effect of
      different body positions on measurement error. Gender was found to have a
      significant effect on the values measured (67 versus 17 per cent of variables
      related to distances in CVC versus VCV sequences and 38 versus 75 per cent of
      variables related to intervals in CVC versus VCV sequences). This finding did
      not, however, hold true for any of the other parameters investigated as potential
      influencing factors. EMA is capable of providing valuable information about lip
      and tongue movements and any pathological dysfunctions involved.

PMID- 21873272
TI  - Clinical outcome of patients with various advanced cancer types vaccinated with
      an optimized cryptic human telomerase reverse transcriptase (TERT) peptide:
      results of an expanded phase II study.
AB  - BACKGROUND: TERT (telomerase reverse transcriptase) plays a critical role in
      tumor cell growth and survival. In an expanded phase II study, we evaluated the
      immunological and clinical responses to the TERT-targeting Vx-001 vaccine in
      patients with advanced solid tumors. METHODS: HLA-A*0201-positive patients
      received two subcutaneous injections of the optimized TERT(572Y) peptide followed
      by four injections of the native TERT(572) peptide, every 3 weeks. Peptide
      specific immune responses were evaluated by enzyme-linked immunosorbent spot at
      baseline, and after the second and the sixth vaccinations. RESULTS: Fifty-five
      patients were enrolled and 34 (62%) completed the six vaccinations. A TERT
      specific T-cell immune response was observed in 55% and 70% of patients after the
      second and the sixth vaccinations, respectively. The disease control rate (DCR)
      was 36% [95% confidence interval (CI) 24% to 49%], including one complete and one
      partial response. Immunologically responding patients had a better clinical
      outcome than nonresponders [DCR: 44% versus 14% (P = 0.047); progression-free
      survival (PFS): 5.2 versus 2.2 months (P = 0.0001) and overall survival: 20
      versus 10 months (P = 0.041)]. Multivariate analysis revealed that the
      immunological response was an independent variable associated with increased PFS
      (hazard ratio = 3.35; 95% CI 1.7-6.7). CONCLUSION: Vx-001 vaccine was well
      tolerated and induced a TERT-specific immunological response, which was
      significantly correlated with improved clinical outcome.

PMID- 21873273
TI  - Salivary protein profiles and sensitivity to the bitter taste of caffeine.
AB  - The interindividual variation in the sensitivity to bitterness is attributed in
      part to genetic polymorphism at the taste receptor level, but other factors, such
      as saliva composition, might be involved. In order to investigate this, 2 groups
      of subjects (hyposensitive, hypersensitive) were selected from 29 healthy male
      volunteers based on their detection thresholds for caffeine, and their salivary
      proteome composition was compared. Abundance of 26 of the 255 spots detected on
      saliva electrophoretic patterns was significantly different between hypo- and
      hypersensitive subjects. Saliva of hypersensitive subjects contained higher
      levels of amylase fragments, immunoglobulins, and serum albumin and/or serum
      albumin fragments. It also contained lower levels of cystatin SN, an inhibitor of
      protease. The results suggest that proteolysis occurring within the oral cavity
      is an important perireceptor factor associated to the sensitivity to the bitter
      taste of caffeine.

PMID- 21873274
TI  - Plastering the head with crushed snails to treat pediatric hydrocephalus: an
      ancient therapy with a pharmacological basis.
AB  - In the Middle Ages, medical therapy for pediatric hydrocephalus was characterized
      by the application of drying substances to decrease the size of the heads of
      affected children. A poultice of crushed snails applied to the head was
      considered to be one of the most powerful therapies for reducing swelling caused
      by excessive humors. Incunabula (texts printed in Europe before 1501 CE) and
      Renaissance texts document the extended use of this therapy, which was considered
      by physicians to be effective and less dangerous than surgical treatment.

PMID- 21873275
TI  - Perceived benefits of mentoring in pediatric psychology: a qualitative approach.
AB  - OBJECTIVE: To identify tangible and intangible benefits of mentoring cited by a
      select group of identified mentors. METHODS: Twenty frequently named mentors
      within pediatric psychology provided responses to open-ended questions regarding
      benefits they have experienced through the mentoring process. RESULTS: Mentors
      identified many personal and professional benefits of the mentoring relationship,
      although they did not clearly distinguish between tangible and intangible
      advantages to the relationship. The most commonly reported benefits included
      career development of the mentee, mentor's career enhancement, and a sense of
      giving back to the field of pediatric psychology. CONCLUSIONS: A bidirectional
      definition of mentoring more accurately describes the relationship than a more
      traditional unidirectional definition. These results suggest that mentors
      experience a wide variety of benefits that could be examined more closely within
      the field.

PMID- 21873276
TI  - Health behaviour and health awareness in infant mortality in the Gaza Strip.
AB  - BACKGROUND: Infant death rate has declined over the past decades, yet remains
      high in Palestine. The topic of infant death is well researched and for the first
      time in Palestine. The objective of our study is to assess the level of awareness
      and health behaviour of mothers and how this behaviour has affected infant
      mortality. METHODS: Person to person interviews were done with 550 mothers of
      infants (275 cases and 275 controls) in the Gaza Strip. Stillbirths were
      excluded. Binary logistic regression analyses were used to identify the
      relationship of health behavioural factors and infant mortality. RESULT: The
      study showed that infant mortality risks were higher in mothers exposed to
      passive smoking. Infant mortality was lower for infants receiving exclusive
      breastfeeding. There was also a significant association between the sleeping
      position of the baby and infant mortality. CONCLUSION: The findings underscore
      the importance of explicit attention to health education. A well-organized
      consultation and health promotion approach should focus on couples whose child
      has died, in order to combat infant mortality.

PMID- 21873277
TI  - Parental knowledge, attitudes and behaviours towards influenza A/H1N1 in Italy.
AB  - BACKGROUND: This study assesses the level of knowledge, the attitudes and the
      behaviours relating to influenza A/H1N1 among parents in Italy. METHODS: A random
      sample of 1299 parents aged 26-65 years received a self-reported questionnaire
      including questions about socio-demographic characteristics, knowledge on modes
      of transmission and preventative measures, attitudes and behaviours relating to
      influenza A/H1N1. RESULTS: A total of 781 subjects participated with a response
      rate of 60.1%. Only 32.3% of the respondents correctly identified the main modes
      of transmission and the main preventative measures, and the results of the
      multivariate logistic regression analysis showed that this knowledge was
      significantly higher in those with a higher level of education and working as
      health-care personnel. The average level of perceived risk of contracting
      influenza A/H1N1 was 4.6 and the multivariate linear regression model showed that
      a greater perceived risk was significantly associated with being unmarried,
      having more than one son, not working in the health-care setting and needing
      additional information about influenza A/H1N1. Less than one-third (28.8%) of the
      respondents had visited a physician at least once in 2 months preceding the
      survey for any reason related to the influenza A/H1N1 and the multivariate
      logistic regression model indicated that females and those with more than one son
      were more likely to have a visit. CONCLUSION: Knowledge about influenza A/H1N1 is
      poor and the results could have significant implications for information
      provision and the targeting of future education programmes to this population.

PMID- 21873278
TI  - How do patients from eastern and western Germany compare with regard to their
      preferences for shared decision making?
AB  - BACKGROUND: Increasing emphasis is being placed on involving patients in
      decisions concerning their health. This shift towards more patient engagement by
      health professionals and towards more desire by patients for participation may be
      partly based on socio-political factors. METHODS: To compare the preferences for
      shared decision making of patients from eastern and western Germany we analysed
      five patient samples (n = 2318) (general practice patients and schizophrenia
      patients from eastern and western Germany). Patients' role preferences for shared
      decisions were measured using the decision-making subscale of the Autonomy
      Preference Index. RESULTS: Patients resident in eastern Germany expressed lower
      preferences for shared decision making than patients in western Germany. This was
      true after controlling for socio-demographic variables and for patient group.
      CONCLUSION: The cultural imprint (e.g. western vs. former communist society)
      seems to have a significant influence on patients' expectations and behaviour in
      the medical encounter. Health services providers need to be aware that health
      attitudes within the same health system might vary for historical and cultural
      reasons. The engagement of patients in medical decisions might not be susceptible
      to a 'one size fits all' approach; doctors should instead aim to accommodate the
      individual patient's desire for autonomy.

PMID- 21873279
TI  - Surgical treatment of neurologic complications of bacterial meningitis in
      children in Kosovo.
AB  - Neurologic complications of bacterial meningitis can occur any time during the
      course of the disease and some of them need neurosurgical aproach. OBJECTIVE: to
      determine the incidence of neurologic complications of bacterial meningitis in
      children requring neurosurgical treatment. MATERIAL AND METHODOLOGY: a total of
      277 children were followed and treated for bacterial meningitis at the Clinic of
      Infectious Diseases in Prishtina. The authors have analyzed cases who developed
      acute neurologic complications and treatment procedures. RESULTS: of the 277
      children treated for bacterial meningitis, due to the suspicion for neurologic
      complications, 109 children underwent a head computerized tomography scan. About
      47 cases (43%) had evident structural abnormalities while only 15/277 cases (5%)
      required neurosurgical treatment; 9/38 cases with subdural collections, 5 cases
      with hydrocephalus and 1 case of spinal abscess. CONCLUSION: Neurosurgical
      intervention were not common in pediatric bacterial meningitis cases (5%) but
      were highly significant in cases complicated with acute neurologic complications
      (32%).

PMID- 21873280
TI  - The "Village" model: a consumer-driven approach for aging in place.
AB  - PURPOSE OF THE STUDY: This study examines the characteristics of the "Village"
      model, an innovative consumer-driven approach that aims to promote aging in place
      through a combination of member supports, service referrals, and consumer
      engagement. DESIGN AND METHODS: Thirty of 42 fully operational Villages completed
      2 surveys. One survey examined Villages' member characteristics, membership
      types, and fee structures. An additional survey collected information about
      organizational mission, goals, methods of operation, funding sources, challenges,
      and older adults' roles. RESULTS: Villages provide a variety of support services
      designed to help members age in place, meet service needs, and promote health and
      quality of life. Most Villages operate relatively autonomously, relying primarily
      on member fees and donations. Village members typically are highly involved in
      organizational development and oversight and provide services to other members in
      almost half of the Villages. Members predominantly are aged 65 years or older,
      White, non-Hispanic, homeowners, and have care needs that are slightly lower than
      those of the elderly U.S. population overall. IMPLICATIONS: Villages are a
      promising model for addressing service needs among middle-class seniors who seek
      to age in their own homes and communities. Financial sustainability is apt to be
      a challenge unless Villages secure more stable sources of funding. Organizational
      sustainability may be promoted through affiliations with social service agencies
      and other sources of technical and financial assistance. Future evaluation is
      needed regarding the impact of Villages on elders' ability to age in place as
      well as the long-term sustainability of the Village model.

PMID- 21873281
TI  - Living with a mentally ill parent: exploring adolescents' experiences and
      perspectives.
AB  - Although a considerable body of research has described the implications of
      parental mental illness, the perspectives of children and adolescents have rarely
      been addressed. In this article, I explore adolescents' experiences in everyday
      life, based on an action-oriented study of a Norwegian online self-help group for
      adolescents (aged 15 to 18) with mentally ill parents. The analysis was conducted
      through participant observation of the group for 2 years. The adolescents
      experienced a variety of difficult challenges related to their parent's mental
      illness: lack of information and openness; unpredictability and instability;
      fear; loneliness; and loss and sorrow. However, they also discussed strategies
      for active management of the challenges arising from the family situation. I
      argue that these adolescents can be understood as vulnerable as well as active
      participants in managing their everyday lives. I emphasize the importance of
      including perspectives of children and adolescents in further research so as to
      improve health care for families with parental mental illness.

PMID- 21873282
TI  - Exploring challenges to telehealth communication by specialists in poison
      information.
AB  - The use of the telephone for providing health care is growing. A significant
      amount of social meaning is derived from visual information, and the absence of
      visual stimuli provides unique barriers to communication and increases the risks
      for misunderstandings and distractions. Understanding challenges to telephone
      communication can provide insight into training opportunities for overcoming
      these difficulties and improving patient care. The purpose of this research was
      to explore through focus groups the challenges of phone communication perceived
      by specialists in poison information. General types of challenges to effective
      phone communication included developing new communication skills to compensate
      for lack of visual information, difficulty assessing caller understanding,
      difficulty managing caller misunderstandings, maintaining distinctive assessments
      for routine calls, and managing the multifaceted aspects of job stress. The
      desire for training to enhance telehealth and cultural competency skills was also
      mentioned, and these findings might provide guidance for the development of
      training opportunities for telehealth professionals.

PMID- 21873283
TI  - Nurses' clinical reasoning: processes and practices of medication safety.
AB  - In this article, we describe the depth of knowledge and skill nurses used in
      making decisions regarding the safe processes and practices of medication
      administration. Using grounded theory, we identified the essence of medication
      safety by nurses as the theme of clinical reasoning. Nurses used two medication
      safety processes within the clinical reasoning theme-maintaining medication
      safety and managing the environment-together with six categories of patient
      focused medication safety practices in the first process and four categories of
      environmental-focused safety practices within the second process. These processes
      and practices present an emerging model of safe medication administration
      developed from the narratives of 50 medical-surgical nurses. This model provides
      researchers with the basis for the development of systemic policies for safer
      medication administration for patients. Health care professional educators might
      also find the results useful in developing curricula focused on patient safety as
      the foundation of quality care.

PMID- 21873284
TI  - Staying safe from hepatitis C: engaging with multiple priorities.
AB  - Hepatitis C virus (HCV) infection is a significant global public health problem.
      In developed countries, 90% of new infections occur among people who inject drugs
      (PWID), with seroprevalence increasing rapidly among new injectors. Staying Safe
      is an international, qualitative, social research project, the aim of which is to
      draw on the experiences of long-term PWID to inform a new generation of HCV
      prevention strategies. The Sydney project team employed life history interviews
      and computer-generated timelines to elicit detailed data about unexposed
      participants' (n =13) injecting practices, circumstances, and social networks
      over time. The motivations and strategies that enabled participants to avoid risk
      situations, and which might have helped them to "stay safe," appeared not to be
      directly related to harm-reduction messages or HCV avoidance. These included the
      ability and inclination to maintain social and structural resources, to mainly
      inject alone, to manage withdrawal, and to avoid injecting-related scars. These
      findings point to the multiple priorities that facilitate viral avoidance among
      PWID and the potential efficacy of nonspecific HCV harm-reduction interventions
      for HCV prevention.

PMID- 21873285
TI  - Carrying: parental experience of the hospital transfer of their baby.
AB  - Some hospital practices that are routine for hospital staff may carry unintended
      significance for patients and their families. The transfer of neonatal infants
      between hospitals and hospital environments is one such practice that may be
      covered by perfectly acceptable rules and regulations but that, at times, gives
      rise to unsuspected anxieties, pain, and worries in the parent. In this
      phenomenological study, I explored meaning aspects of the phenomenon transfer to
      reveal a lived experience of carrying--a carrying across from here to there; a
      carrying between changing places; a carrying contact of parent-child in-touchness
      that is enabled or compromised in this experience; a carrying with care; and a
      carrying as a search for place as home. The concluding recommendations speak to
      the need for understanding the experiences of hospitalized babies' parents, and
      speak to the tactful sensitivities required of the health care team during the
      transfer of child and family.

PMID- 21873286
TI  - Feeling their stories: contemplating empathy, insider/outsider positionings, and
      enriching qualitative research.
AB  - Empathy is a very familiar term in the helping and caring literature. What
      appears to link empathy in the helping literature to the aims and goals of
      qualitative research and, in particular, to the argument underpinning
      insider/outsider debates, is a discernible common quest. That quest is to be able
      to hear, feel, understand, and value the stories of others and to convey that
      felt empathy and understanding back to the client/storyteller/participant. When
      relevant, the quest also includes conveying that felt understanding to a broader
      audience. In this article, I highlight commonalities between empathy in
      professional practice and empathy in qualitative research processes, including
      the shared experiences and understanding informing research relationships that
      are discussed as "insider/outsider" status. I review, discuss, and critique
      relevant literature, and I conclude by suggesting that cultivating empathy in
      qualitative research training could contribute to facilitating more enriched,
      insightful research encounters.

PMID- 21873287
TI  - AbaR4 replaces AbaR3 in a carbapenem-resistant Acinetobacter baumannii isolate
      belonging to global clone 1 from an Australian hospital.
AB  - OBJECTIVES: To explore the diversity of genomic resistance islands in multiply
      antibiotic-resistant Acinetobacter baumannii isolates in global clone 1 (GC1)
      from Australian hospitals. METHODS: PCR was used to characterize isolates, detect
      antibiotic resistance genes and insertion sequences and screen for genomic
      resistance islands. Structures of genomic islands were determined by PCR mapping
      and sequencing. Multilocus sequence typing was performed using the Oxford scheme.
      RESULTS: Eleven isolates that belong to GC1 were found among 90 A. baumannii
      isolated between 2001 and 2010 at Australian hospitals, and 5 were carbapenem
      resistant. Ten isolates had the features characteristic of AbaR3 and related
      islands, but one carbapenem-resistant isolate did not. Instead, D36 carried the
      bla(OXA-23) gene in transposon Tn2006, with Tn2006 in AbaR4, and AbaR4 in the
      chromosomal comM gene, replacing the AbaR3-type island usually associated with
      multiply antibiotic-resistant GC1 isolates. D36 was resistant to gentamicin,
      kanamycin and tobramycin due to the aadB gene cassette in the context found in
      plasmid pRAY and to sulfamethoxazole due to the sul2 gene. D36 was of a rare
      sequence type (ST), ST247. Bioinformatic analysis identified five potential
      transposition genes in the AbaR backbone transposons. CONCLUSIONS: Substantial
      diversity was observed among the GC1 isolates. This is the first report of AbaR4
      replacing the AbaR3-type island seen in most GC1 isolates, and D36 represents a
      distinct new GC1 lineage. The AbaRs are members of a large, previously
      undocumented family of transposons that target comM.

PMID- 21873288
TI  - Predominance of sequence type 1 group with serotype VI among group B streptococci
      with reduced penicillin susceptibility identified in Japan.
AB  - BACKGROUND: Although group B Streptococcus (GBS; i.e. Streptococcus agalactiae)
      has been considered to be uniformly susceptible to beta-lactams, GBS isolates
      with reduced penicillin susceptibility (PRGBS) have been reported from Japan and
      North America. In this study, PRGBS from Japan were characterized by multilocus
      sequence typing (MLST) and the results compared with data on PRGBS reported from
      the USA. METHODS: Twenty-eight clinical isolates of PRGBS recovered in Japan
      (including 22 isolates previously analysed by PFGE) were analysed by MLST and
      eBURST (http://eburst.mlst.net/). RESULTS: Twenty-three isolates were found to
      belong to the sequence type 1 (ST1) group (11 ST458, 7 ST1, 3 ST297, 1 ST358 and
      1 ST4), while the remaining 5 isolates formed the ST23 group. Among 11 ST458 and
      7 ST1 isolates, 9 and 4 were serotype VI, respectively, indicating a probable
      correlation between the ST1 group and serotype VI for PRGBS in Japan.
      CONCLUSIONS: PRGBS in Japan could be classified into at least two ST groups, ST1
      and ST23, which are genetically different from the ST19 PRGBS isolated in the
      USA, though five allele variations were seen between ST1 and ST19, implying a
      slight genetic relatedness.

PMID- 21873289
TI  - Combinatorial activities of ionic silver and sodium hexametaphosphate against
      microorganisms associated with chronic wounds.
AB  - OBJECTIVES: There is growing evidence to suggest that biofilms may be involved in
      the aetiology of chronic wounds. The development of formulations with enhanced
      anti-biofilm activity could therefore represent a potential therapeutic strategy
      by reducing bioburdens. Here, the antimicrobial properties of ionic silver and
      sodium hexametaphosphate (polyphosphate) against bacteria in planktonic form and
      as biofilms were investigated. METHODS: The MICs, MBCs and minimum biofilm
      eradication concentrations (MBECs) of the two test compounds against Candida
      albicans, Pseudomonas aeruginosa and Staphylococcus aureus were determined. The
      chequerboard microdilution method was used to determine the fractional inhibitory
      concentration index (FICI) and fractional biofilm eradication concentration index
      (FBCI) for the compounds against planktonic bacteria and monospecies biofilms. In
      addition, biofilms in continuous culture were exposed to hydrogel formulations
      containing ionic silver and polyphosphate, singly or in combination. RESULTS:
      Ionic silver and polyphosphate, when combined, exhibited putative anti-biofilm
      synergy against P. aeruginosa (FBCI 0.08), C. albicans (FBCI 0.06) and S. aureus
      (FBCI 0.44). While silver hydrogels reduced the viability of continuous culture
      biofilms, the incorporation of polyphosphate resulted in significantly greater
      and more rapid bacterial inactivation (P < 0.05). CONCLUSIONS: The antimicrobial
      and anti-biofilm potency of silver hydrogels was markedly enhanced by the
      incorporation of polyphosphate.

PMID- 21873290
TI  - Molecular analysis of the effector mechanisms of cefoxitin resistance among
      Bacteroides strains.
AB  - OBJECTIVES: The characterization of Bacteroides strains with regard to the cfxA
      gene, the MTn4555 mobilizable transposon, the role of penicillin-binding proteins
      (PBPs) and heterogeneous cefoxitin resistance. METHODS: Eighty-four randomly
      selected and 11 heterogeneously or highly cefoxitin-resistant Bacteroides
      isolates were included. Agar dilution and Etest methods were used for the
      determination of cefoxitin MICs. PCR experiments and nucleotide sequencing were
      used to detect the cfxA gene and the molecular features of MTn4555. Cefoxitin
      binding experiments to determine its affinity (IC(50)) for PBPs and cefoxitinase
      assays were also applied. Southern blotting was used to determine the copy number
      of the cfxA genes. RESULTS: Sixteen strains from the random collection proved to
      be positive for cfxA, and the MIC distribution for the cfxA-negative and 
      positive strains did not display a clear separation. The majority of the cfxA
      positive strains in this collection harboured a 1.2 kb common region at the 3'
      end of MTn4555. This region encoded an open reading frame that exhibited homology
      to abortive phage infection proteins (AbiD). The cfxA genes were transferable
      only at low frequencies in conjugation experiments. In PBP affinity studies, the
      PBP-A and PBP3 species were largely insensitive to cefoxitin, whereas the other
      PBP species were affected at very low concentrations. Seven of the
      heterogeneously resistant strains were positive for cfxA and most of them had
      mutations in the regulatory regions of cfxA. CONCLUSIONS: Major and minor roles
      for Bacteroides fragilis PBPs and the CfxA cefoxitinase, respectively, were
      inferred. The role of the newly recognized abiD may be to control the copy number
      of cfxA.

PMID- 21873291
TI  - Pre-clinical development of antifungal susceptibility test methods for the
      testing of the novel antifungal agent E1210 versus Candida: comparison of CLSI
      and European Committee on Antimicrobial Susceptibility Testing methods.
AB  - OBJECTIVES: To compare European Committee on Antimicrobial Susceptibility Testing
      (EUCAST) and CLSI broth microdilution (BMD) methods for testing the novel
      antifungal E1210 against a recent collection of 102 clinical isolates of Candida
      spp. METHODS: Candida isolates (102) were tested by CLSI and EUCAST methods; 21
      Candida albicans, 20 Candida glabrata, 25 Candida parapsilosis, 24 Candida
      tropicalis and 12 Candida krusei, including echinocandin- and azole-resistant
      isolates. CLSI and EUCAST MIC endpoints of 50% and 100% inhibition were
      determined using visual reading at 24 and 48 h of incubation and
      spectrophotometric reading at 24 h of incubation, respectively. RESULTS: E1210
      CLSI MIC results ranged from <=0.008 to only 1 mg/L (excluding C. krusei)
      depending on species, duration of incubation and endpoint criteria (EC). E1210
      was not active against C. krusei (MIC(50) >16 mg/L). Overall essential agreement
      (EA; +/-2 doubling dilutions) between the 24 and 48 h CLSI readings was 100% and
      97.6% using the 50% and 100% inhibition EC, respectively. Slightly more trailing
      growth at 48 h was observed with the 100% inhibition EC. Comparison of the 50%
      and 100% endpoints at 24 h of incubation showed an overall EA of 100%. Comparison
      of CLSI and EUCAST read at 24 h of incubation and either 50% or 100% inhibition
      revealed an EA of 97.8% using the 50% inhibition EC and 88.9% using the 100%
      inhibition EC. CONCLUSIONS: E1210 was found to have potent in vitro activity
      against Candida spp. when tested by both CLSI and EUCAST BMD methods, with the
      highest overall EA (97.8%) obtained when E1210 MIC results were read after 24 h
      of incubation using a partial inhibition EC.

PMID- 21873293
TI  - Comparative study of the experience of caregiving in bipolar affective disorder
      and schizophrenia.
AB  - BACKGROUND: Bipolar affective disorder and schizophrenia are disabling illnesses
      and place a considerable degree of burden on the caregivers. Many studies from
      India have measured the burden of care in schizophrenia and some studies have
      measured the burden experienced by the caregivers of bipolar affective disorder.
      Few studies have compared this variable in these disorders. Experience of
      caregiving is a broader concept that takes into consideration both the negative
      and positive appraisal of the caregiving. However, no study from India has
      compared the experience of caregiving in bipolar affective disorder and
      schizophrenia. AIM OF THE STUDY: To study the experience of caregiving in a group
      of caregivers of bipolar patients and compare the same with caregivers of
      patients with schizophrenia. METHOD: Seventy patients with a diagnosis of bipolar
      affective disorder and 70 with a diagnosis of schizophrenia were selected for the
      present study. Patients were assessed on the Hamilton Depression Rating Scale,
      the Young Mania Rating Scale and the Positive and Negative Syndrome Scale
      depending upon their diagnosis. They were also assessed on the Global Assessment
      of Functioning (GAF) scale. Caregivers of the patients were assessed on the
      General Health Questionnaire (GHQ) and the Experience of Caregiving Inventory
      (ECI). RESULTS: The maximum ECI score was seen in the domain of handling
      'difficult behaviour' in both the groups. Compared to caregivers of patients with
      bipolar affective disorder, caregivers of patients with schizophrenia had overall
      more positive and negative appraisal of caregiving experience while caring for
      their ill relatives. The difference reached significant levels for all domains
      but for the domains of 'effects on family', 'need for back-up' and 'good aspect
      of relationship'. There were significant differences too for the total positive
      personal experience sub-score. There was a significant positive correlation
      between the negative and positive caregiving experience score for both
      schizophrenia and bipolar groups. CONCLUSION: The caregivers of both bipolar
      affective disorder and schizophrenia appraise the caregiving negatively, while at
      the same time appraising some positive aspects of it. Caregivers of schizophrenia
      patients appraise caregiving more negatively than those of bipolar affective
      disorder patients.

PMID- 21873292
TI  - Psychological distress in Canada: the role of employment and reasons of non
      employment.
AB  - BACKGROUND: This study investigated variations in psychological distress in a
      large sample of the Canadian population according to employment status,
      occupation, work organization conditions, reasons for non-employment, stress and
      support outside the work environment, family situation and individual
      characteristics. METHODS: Data came from cycle 4 (2000-1) of the Canadian
      National Population Health Survey conducted by Statistics Canada. Multiple
      regression analyses, adjusted for the family situation, the level of support from
      the social network and the individual characteristics, were carried out on a
      sample of 7258 individuals aged from 18 to 65 years. RESULTS: Occupation, social
      support at work, age, self-esteem, presence of children aged five and under and
      social support outside of the workplace were associated with lower levels of
      psychological distress, while permanent and temporary disability, psychological
      demands in the workplace, job insecurity, female gender, and stressful financial,
      marital and parental situations were related to higher levels of psychological
      distress. CONCLUSIONS: Findings from this study suggest that, in terms of
      psychological distress, having a job is not always better than non-employment,
      and that specific non-employment situations associate differently with
      psychological distress.

PMID- 21873294
TI  - Differential mRNA translation in Medicago truncatula accessions with contrasting
      responses to ozone-induced oxidative stress.
AB  - Acute ozone is a model abiotic elicitor of oxidative stress and a useful tool for
      understanding biochemical and molecular events during oxidative signaling. Two
      Medicago truncatula accessions with contrasting responses to ozone were used to
      examine translational regulation during ozone stress. In ozone-resistant JE154,
      significant reduction in ribosome loading was observed within one hour of ozone
      treatment, suggesting energy homeostasis as a vital factor for oxidative stress
      management. Polysomal RNA-based expression profiling with Affymetrix arrays
      revealed extensive changes in the translatomes of both accessions. Messenger RNAs
      with low GC content in their 5' and 3'-UTRs were preferentially associated with
      polysomes during oxidative stress. Genebins analysis revealed extensive changes
      in various gene ontologies in both accessions. Extensive changes in nicotinate
      and nicotinamide metabolism genes were corroborated with increased levels of
      NAD(+) and NADH in JE154. The significantly lower NAD(+):NADH redox status in
      JE154, in conjunction with higher ATP amounts, provided a cellular milieu
      conducive for overcoming oxidative stress. Low levels of ATP, NADH, and
      suppression of antioxidant defense responses, abet build-up of ozone-derived ROS
      and ultimately lead to oxidative cell death in Jemalong.

PMID- 21873295
TI  - Live-cell imaging of dual-labeled Golgi stacks in tobacco BY-2 cells reveals
      similar behaviors for different cisternae during movement and brefeldin A
      treatment.
AB  - In plant cells, the Golgi apparatus consists of numerous stacks that, in turn,
      are composed of several flattened cisternae with a clear cis-to-trans polarity.
      During normal functioning within living cells, this unusual organelle displays a
      wide range of dynamic behaviors such as whole stack motility, constant membrane
      flux through the cisternae, and Golgi enzyme recycling through the ER. In order
      to further investigate various aspects of Golgi stack dynamics and integrity, we
      co-expressed pairs of established Golgi markers in tobacco BY-2 cells to
      distinguish sub-compartments of the Golgi during monensin treatments, movement,
      and brefeldin A (BFA)-induced disassembly. A combination of cis and trans markers
      revealed that Golgi stacks remain intact as they move through the cytoplasm. The
      Golgi stack orientation during these movements showed a slight preference for the
      cis side moving ahead, but trans cisternae were also found at the leading edge.
      During BFA treatments, the different sub-compartments of about half of the
      observed stacks fused with the ER sequentially; however, no consistent order
      could be detected. In contrast, the ionophore monensin resulted in swelling of
      trans cisternae while medial and particularly cis cisternae were mostly
      unaffected. Our results thus demonstrate a remarkable equivalence of the
      different cisternae with respect to movement and BFA-induced fusion with the ER.
      In addition, we propose that a combination of dual-label fluorescence microscopy
      and drug treatments can provide a simple alternative approach to the
      determination of protein localization to specific Golgi sub-compartments.

PMID- 21873296
TI  - Myosin VIII regulates protonemal patterning and developmental timing in the moss
      Physcomitrella patens.
AB  - Plants have two classes of myosins. While recent work has focused on class XI
      myosins showing that myosin XI is responsible for organelle motility and
      cytoplasmic streaming, much less is known about the role of myosin VIII in plant
      growth and development. We have used a combination of RNAi and insertional
      knockouts to probe myosin VIII function in the moss Physcomitrella patens. We
      isolated Deltamyo8ABCDE plants demonstrating that myosin VIII is not required for
      plant viability. However, myosin VIII mutants are smaller than wild-type plants
      in part due to a defect in cell size. Additionally, Deltamyo8ABCDE plants produce
      more side branches and form gametophores much earlier than wild-type plants. In
      the absence of nutrient media, Deltamyo8ABCDE plants exhibit significant
      protonemal patterning defects, including highly curved protonemal filaments,
      morphologically defective side branches, as well as an increase in the number of
      branches. Exogenous auxin partially rescues protonemal defects in Deltamyo8ABCDE
      plants grown in the absence of nutrients. This result, together with defects in
      protonemal branching, smaller caulonemal cells, and accelerated development in
      the Deltamyo8ABCDE plants, suggests that myosin VIII is involved in hormone
      homeostasis in P. patens.

PMID- 21873297
TI  - Adaptive evolution of a novel Drosophila lectin induced by parasitic wasp attack.
AB  - Drosophila melanogaster has long been used as a model for the molecular genetics
      of innate immunity. Such work has uncovered several immune receptors that
      recognize bacterial and fungal pathogens by binding unique components of their
      cell walls and membranes. Drosophila also act as hosts to metazoan pathogens such
      as parasitic wasps, which can infect a majority of individuals in natural
      populations, but many aspects of their immune responses against these more
      closely related pathogens are poorly understood. Here, we present data describing
      the transcriptional induction and molecular evolution of a candidate Drosophila
      anti-wasp immunity gene, lectin-24A. Lectin-24A has a secretion signal sequence
      and its lectin domain suggests a function in sugar group binding. Transcript
      levels of lectin-24A were induced significantly stronger and faster following
      wasp attack than following wounding or bacterial infection, demonstrating lectin
      24A is not a general stress response or defense response gene but is instead part
      of a specific response against wasps. The major site of lectin-24A transcript
      production is the fat body, the main humoral immune tissue of flies.
      Interestingly, lectin-24A is a new gene of the D. melanogaster/Drosophila
      simulans clade, displaying very little homology to any other Drosophila lectins.
      Population genetic analyses of lectin-24A DNA sequence data from African and
      North American populations of D. melanogaster and D. simulans revealed gene
      length polymorphisms segregating at high frequencies as well as strong evidence
      of repeated and recent selective sweeps. Thus, lectin-24A is a rapidly evolving
      new gene that has seemingly developed functional importance for fly resistance
      against infection by parasitic wasps.

PMID- 21873300
TI  - Organizational factors and the attitude toward health promotion in German ICT
      companies.
AB  - This study takes a first step toward examining the relationship between
      organizational characteristics and the perceived attitude toward health promotion
      in companies from the perspective of chief executive officers (CEOs). Data for
      the cross-sectional study were collected through telephone interviews with one
      CEO from randomly selected companies within the German information and
      communication technology (ICT) sector. Multivariate logistic regression analysis
      (LRA) was performed, and further LRA was conducted after stratifying on company
      size. LRA of data from a total of n = 522 interviews found significant
      associations between the attitude toward health promotion and the company's
      market position, its number of hierarchical levels, the percentage of permanent
      positions and the percentage of employees with an academic education. After
      stratification on company size, the association between the attitude toward
      health promotion and both market position and the percentage of employees with an
      academic education was still present in small companies. There were no
      significant relationships between the attitude toward health promotion and the
      structural characteristics of medium-sized and large companies. The preliminary
      results of the study indicate that a perceived attitude toward health promotion
      in companies can be explained, to a certain degree, by the intraorganizational
      characteristics analyzed. Our key findings highlight that efforts toward
      establishing a positive attitude toward health promotion should focus on small
      companies with a lower market position and a greater number of employees with a
      lower education level.

PMID- 21873301
TI  - Bayesian hierarchical Poisson models with a hidden Markov structure for the
      detection of influenza epidemic outbreaks.
AB  - Considerable effort has been devoted to the development of statistical algorithms
      for the automated monitoring of influenza surveillance data. In this article, we
      introduce a framework of models for the early detection of the onset of an
      influenza epidemic which is applicable to different kinds of surveillance data.
      In particular, the process of the observed cases is modelled via a Bayesian
      Hierarchical Poisson model in which the intensity parameter is a function of the
      incidence rate. The key point is to consider this incidence rate as a normal
      distribution in which both parameters (mean and variance) are modelled
      differently, depending on whether the system is in an epidemic or non-epidemic
      phase. To do so, we propose a hidden Markov model in which the transition between
      both phases is modelled as a function of the epidemic state of the previous week.
      Different options for modelling the rates are described, including the option of
      modelling the mean at each phase as autoregressive processes of order 0, 1 or 2.
      Bayesian inference is carried out to provide the probability of being in an
      epidemic state at any given moment. The methodology is applied to various
      influenza data sets. The results indicate that our methods outperform previous
      approaches in terms of sensitivity, specificity and timeliness. 

PMID- 21873302
TI  - A likelihood-based two-part marginal model for longitudinal semicontinuous data.
AB  - Two-part models are an attractive approach for analysing longitudinal
      semicontinuous data consisting of a mixture of true zeros and continuously
      distributed positive values. When the population-averaged (marginal) covariate
      effects are of interest, two-part models that provide straightforward
      interpretation of the marginal effects are desirable. Presently, the only
      available approaches for fitting two-part marginal models to longitudinal
      semicontinuous data are computationally difficult to implement. Therefore, there
      exists a need to develop two-part marginal models that can be easily implemented
      in practice. We propose a fully likelihood-based two-part marginal model that
      satisfies this need by using the bridge distribution for the random effect in the
      binary part of an underlying two-part mixed model; and its maximum likelihood
      estimation can be routinely implemented via standard statistical software such as
      the SAS NLMIXED procedure. We illustrate the usage of this new model by
      investigating the marginal effects of pre-specified genetic markers on physical
      functioning, as measured by the Health Assessment Questionnaire, in a cohort of
      psoriatic arthritis patients from the University of Toronto Psoriatic Arthritis
      Clinic. An added benefit of our proposed marginal model when compared to a two
      part mixed model is the robustness in regression parameter estimation when
      departure from the true random effects structure occurs. This is demonstrated
      through simulation. 

PMID- 21873298
TI  - Statistics and truth in phylogenomics.
AB  - Phylogenomics refers to the inference of historical relationships among species
      using genome-scale sequence data and to the use of phylogenetic analysis to infer
      protein function in multigene families. With rapidly decreasing sequencing costs,
      phylogenomics is becoming synonymous with evolutionary analysis of genome-scale
      and taxonomically densely sampled data sets. In phylogenetic inference
      applications, this translates into very large data sets that yield evolutionary
      and functional inferences with extremely small variances and high statistical
      confidence (P value). However, reports of highly significant P values are
      increasing even for contrasting phylogenetic hypotheses depending on the
      evolutionary model and inference method used, making it difficult to establish
      true relationships. We argue that the assessment of the robustness of results to
      biological factors, that may systematically mislead (bias) the outcomes of
      statistical estimation, will be a key to avoiding incorrect phylogenomic
      inferences. In fact, there is a need for increased emphasis on the magnitude of
      differences (effect sizes) in addition to the P values of the statistical test of
      the null hypothesis. On the other hand, the amount of sequence data available
      will likely always remain inadequate for some phylogenomic applications, for
      example, those involving episodic positive selection at individual codon
      positions and in specific lineages. Again, a focus on effect size and biological
      relevance, rather than the P value, may be warranted. Here, we present a
      theoretical overview and discuss practical aspects of the interplay between
      effect sizes, bias, and P values as it relates to the statistical inference of
      evolutionary truth in phylogenomics.

PMID- 21873303
TI  - The Minnesota Center Against Violence and Abuse (MINCAVA): providing research,
      education, and access to information on violence against women and children.
AB  - The Minnesota Center Against Violence and Abuse (MINCAVA) was established in 1994
      through an appropriation of the Minnesota Legislature. Located at the University
      of Minnesota, MINCAVA conducts original research, develops extensive collections
      of translational materials, provides higher education training on family violence
      prevention, and disseminates information globally. Over a dozen professional and
      student staff work on projects funded by federal, state, and private sources and
      collaborate closely with national and global advisory boards and partner agencies
      as well as local community-based and national advocacy organizations. The Center
      operates multiple project-specific and general websites that receive millions of
      unique visits each year from dozens of countries.

PMID- 21873304
TI  - The University of Kentucky Center for Research on Violence Against Women: science
      inspired by women's stories.
AB  - Research in the violence against women area has been undertaken for more than 30
      years, but individual researchers who have made these scholarly contributions
      have not been advantaged by adequate attention, funding, or organizational
      structure within the university setting. This article offers a detailed
      description of a model of an interdisciplinary research center designed to
      provide an academic architecture within which research on intimate partner
      violence, sexual assault, stalking, and other forms of violence against women can
      flourish and advance. The article describes the impetus for creation of the
      University of Kentucky Center for Research on Violence Against Women, its current
      mission, organizational structure, financial operations, and initiatives related
      to research, education, and public service. Practical strategies for establishing
      and sustaining a center of this type are offered.

PMID- 21873305
TI  - Injury research: a perspective from the National Center for Injury Prevention and
      Control.

PMID- 21873306
TI  - Prevalence of helmet use by users of bicycles, push scooters, inline skates and
      skateboards in Toronto and the surrounding area in the absence of comprehensive
      legislation: an observational study.
AB  - BACKGROUND: Legislation in the province of Ontario, Canada, mandates users under
      the age of 18 to wear a helmet when they ride a bicycle, and legislation has been
      shown to significantly increase rates of bicycle helmet use. Legislation does not
      exist in Ontario for older bicyclists or for users of other non-motorised modes
      of transportation, and there are no current data available regarding rates of
      helmet use in these categories. This study was designed to determine the
      prevalence of helmet use among users of bicycles, skateboards, push scooters and
      inline skates in Toronto, Ontario, and the surrounding area. Further analysis was
      performed to examine factors associated with helmet use. METHODS: We performed a
      cross-sectional, observational study. Three trained, stationary observers
      captured 6038 users of bicycles (5783), skateboards (77), inline skates (165) and
      push scooters (13) in the summer of 2009. Observations were separated into three
      time periods capturing commuters, midday users and recreational users. A general
      linear model was used to assess the factors associated with helmet use among
      bicyclists. RESULTS: Helmets were worn by 48.9% of all users observed and 50.0%
      of all bicyclists. Among bicyclists, females were more likely to wear helmets
      than males (prevalence ratio 1.27, 95% CI 1.17 to 1.36), while children were
      significantly more likely to wear helmets than adults (prevalence ratio 1.17, 95%
      CI 1.37 to 2.15). Significant behavioural variation was observed among users
      during the three observation periods (p<0.001), with commuters being the most
      likely to wear a helmet. CONCLUSION: In the absence of comprehensive legislation
      encompassing all ages of users, only half of users of non-motorised, wheeled
      transportation devices are choosing to wear a helmet to protect against traumatic
      brain injury. Implementation of evidence-based strategies to increase helmet use,
      such as the introduction of legislation encompassing all ages and all equipment,
      is required.

PMID- 21873307
TI  - Proximity to vacant buildings is associated with increased fire risk in
      Baltimore, Maryland, homes.
AB  - BACKGROUND: Fires and burns are a leading cause of unintentional injury death in
      the USA. Although it has been anecdotally reported that vacant dwellings are at a
      higher risk for fire, the association between vacancy and fire risk at the
      individual household level has not been empirically measured. METHODS: In this
      cross-sectional study, geocoded residential vacant properties (VP) and fire
      events are analysed in Baltimore City at the census tract level and the
      individual household level. RESULTS: On average, a 10% increase in the proportion
      of vacancies in a census tract was associated with a 9.9% increase in fires (95%
      CI: 5% to 15%). Random-effects Poisson models, controlling for housing and
      neighbourhood conditions, found contagion effects. The risk of fire in an
      occupied dwelling increased by 8% (95% CI: 1% to 10%) for every vacant structure
      within 10 m, and the risk of fire decreased by half (95% CI: 45% to 62%) for
      every km between an occupied dwelling and vacant building. Close proximity to VP
      was associated with trash fires within dwellings (p=0.039) and structure fires
      (p=0.012). CONCLUSIONS: We believe that this is the first study to demonstrate
      increased risk posed by nearby VP at the household level, confirming earlier
      ecological analyses of the role of VP as strong correlates of home fires.
      Measurement of this risk can motivate property owners, policy makers and insurers
      to invest in risk reduction measures that include building maintenance and trash
      removal.

PMID- 21873308
TI  - Using human tissue: when do we need consent?
AB  - Identifiable excess surgical tissue is an important resource for medical research
      but we have become overly restrictive about consent requirements. I suggest we
      devolve consent to ethics committees for ordinary research projects involving
      human tissue, retaining the requirement for explicit consent only for those
      sensitive research situations where there is significant risk of harm to
      individual interests in privacy.

PMID- 21873309
TI  - Diagnostic misconceptions? A closer look at clinical research on Alzheimer's
      disease.
AB  - The current focus on early intervention trials in Alzheimer's disease research
      raises particular ethical issues. These arise out of problems of validating study
      results and translating them into general practice for one thing and out of
      unwanted effects of an uncertain diagnosis for diagnosed people for another. The
      first addresses the demands of scientific research compared to those of medical
      practice, questioning how the medical value of clinical trials is evaluated. The
      second relates the scientific and medical value of early intervention trials to
      the normative value of an uncertain diagnosis. Are people who are diagnosed with
      a potential early form of AD in clinical studies patients proper-although they
      would not have been diagnosed with the given "disease" in non-research-oriented
      medical settings? The very problem of framing this question in terms of
      diagnostic misconceptions connects conceptual with ethical issues of research
      into preclinical stages of neurodegenerative diseases.

PMID- 21873310
TI  - The ethics committee as ghost author.

PMID- 21873311
TI  - Decreased accommodation during decompensation of distance exotropia.
AB  - OBJECTIVE: Disparity cues can be a major drive to accommodation via the
      convergence accommodation to convergence (CA/C) linkage, but, on decompensation
      of exotropia, disparity cues are extinguished by suppression so this drive is
      lost. This study investigated accommodation and vergence responses to disparity,
      blur and proximal cues in a group of distance exotropes aged between 4 and 11
      years both during decompensation and when exotropic. METHODS: 19 participants
      with distance exotropia were tested using a PlusoptiXSO4 photo refractor set in a
      remote haploscopic device that assessed simultaneous vergence and accommodation
      to a range of targets incorporating different combinations of blur, disparity and
      proximal cues at four fixation distances between 2 m and 33 cm. Responses on
      decompensation were compared with those from the same children when their
      deviation was controlled. RESULTS: Manifest exotropia was more common in the more
      impoverished cue conditions. When decompensated for near, mean accommodation gain
      for the all-cue (naturalistic) target was significantly reduced (p<0.0001), with
      resultant mean under-accommodation of 2.33 D at 33 cm. The profile of near cues
      usage changed after decompensation, with blur and proximity driving residual
      responses, but these remaining cues did not compensate for loss of accommodation
      caused by the removal of disparity. CONCLUSIONS: Accommodation often reduces on
      decompensation of distance exotropia as the drive from convergence is
      extinguished, providing a further reason to try to prevent decompensation for
      near.

PMID- 21873312
TI  - C5a contributes to intraocular inflammation by affecting retinal pigment
      epithelial cells and immune cells.
AB  - BACKGROUND: The complement activation molecule C5a has been found in the eye and
      is implicated in the pathogenesis of ocular inflammatory diseases. In this study,
      the authors sought to investigate C5a's effects on human retinal pigment
      epithelial (RPE) cells and peripheral blood mononuclear cells (PBMCs), and on the
      interaction between RPE cells and PBMCs. METHODS: Arising retinal pigment
      epithelia cell line-19 and PBMCs isolated from healthy donors were used in this
      study. Western blot, real-time PCR and cell surface receptor staining were used
      to detect C5a receptor expression. Real-time PCR was used to detect cytokine mRNA
      expression. A thiazolyl blue tetrazolium bromide assay was used to detect cell
      viability. Cells were stained with Annexin V and 7-aminoactinomycin D for an
      apoptosis assay. Cell proliferation was measured using a tritiated thymidine
      incorporation assay. RESULTS: C5a receptors were present on RPE cells, and
      receptor expression was increased by pro-inflammatory cytokines. C5a suppressed
      RPE cells' production of transforming growth factor beta2, an important
      immunosuppressive agent in the eye. In addition, the viability of RPE cells was
      decreased in the presence of C5a, and this effect was not due to apoptosis. C5a
      increased proliferation of PBMCs and upregulated their production of pro
      inflammatory cytokines. Finally, C5a decreased RPE cells' ability to suppress
      immune cell proliferation. CONCLUSION: The results provide a direct link between
      complement activation and intraocular inflammation. This line of information may
      help to understand the mechanism of the pathogenesis of intraocular inflammatory
      diseases. Moreover, the authors show that a close, reciprocal interaction between
      the innate immune system and the adaptive immune system may be involved in the
      development of such diseases.

PMID- 21873313
TI  - There is no association of CCR6 polymorphisms with susceptibility to Behcet's
      disease in two Chinese Han populations.
AB  - BACKGROUND: Polymorphisms of CC chemokine receptor 6 (CCR6) genes have recently
      been reported to be associated with the susceptibility to several immune-related
      diseases. This study was conducted to examine the association of CCR6 with
      Behcet's disease (BD) in two Chinese Han populations. METHODS: A total of 473
      patients with BD and 725 healthy controls from two Chinese Han populations were
      genotyped by the PCR-restriction fragment length polymorphism method. Hardy
      Weinberg equilibrium was tested using the chi(2) test. Genotype frequencies were
      estimated by direct counting. Allele and genotype frequencies were compared
      between patients and controls using the chi(2) test. RESULTS: The genotype and
      allele frequencies of rs3093024, rs6902119, rs3093023 and rs2301436 were not
      different between patients with BD and healthy controls. Analysis according to
      gender and clinical findings including oral ulcer, genital ulcer, skin lesions
      and arthritis did not show any association of the four tested polymorphisms with
      these parameters. CONCLUSIONS: The tested CCR6 gene polymorphisms are not
      associated with the susceptibility to BD in the tested Chinese Han populations.

PMID- 21873314
TI  - Development and validation of a computer-aided diagnostic tool to screen for age
      related macular degeneration by optical coherence tomography.
AB  - BACKGROUND: To develop and assess the technical validity of new computer-aided
      diagnostic software (CAD) for automated analyses of optical coherence tomography
      (OCT) images for the purpose of screening for neovascular age-related macular
      degeneration. METHODS: Artificial visual techniques were used to develop the CAD
      in two steps: normalisation and feature vector extraction from OCT images; and
      training and classification by means of decision trees. Technical validation was
      performed by a retrospective study design based on OCT images randomly extracted
      from clinical charts. Images were classified as normal or abnormal to serve for
      screening purposes. Sensitivity, specificity, positive predictive values and
      negative predictive values were obtained. RESULTS: The CAD was able to quantify
      image information by working in the perceptually uniform hue-saturation-value
      colour space. Particle swarm optimisation with Haar-like features is suitable to
      reveal structural features in normal and abnormal OCT images. Decision trees were
      useful to characterise normal and abnormal images using feature vectors obtained
      from descriptive statistics of detected structures. The sensitivity of the CAD
      was 96% and the specificity 92%. CONCLUSIONS: This new CAD for automated analysis
      of OCT images offers adequate sensitivity and specificity to distinguish normal
      OCT images from those showing potential neovascular age-related macular
      degeneration. These results will enable its clinical validation and a subsequent
      cost-effectiveness assessment to be made before recommendations are made for
      population-screening purposes.

PMID- 21873315
TI  - Production of ELOVL4 transgenic pigs: a large animal model for Stargardt-like
      macular degeneration.
AB  - BACKGROUND: Truncation mutations in the elongation of very long chain fatty acids
      4 (AF277094, MIM #605512) (ELOVL4) gene cause Stargardt-like macular dystrophy
      type 3 (STGD3). Mice expressing truncated ELOVL4 develop rapid retinal
      degeneration, but are poor STGD3 models since mice lack a macula. Photoreceptor
      topography in the pig retina is more similar to that in humans as it includes the
      cone rich, macula-like area centralis. The authors generated transgenic pigs
      expressing human disease-causing ELOVL4 mutations to better model the
      pathobiology of this macular disease. METHODS: Pronuclear DNA microinjection and
      somatic cell nuclear transfer were used to produce transgenic pigs for two
      different ELOVL4 mutations: the 5 base pair deletion (5 bpdel) and the 270 stop
      mutation (Y270terEYFP). Retinal transgene expression, morphology and
      electrophysiology were examined. RESULTS: The authors obtained four lines of
      Y270terEYFP and one line of 5 bpdel transgenic animals. Direct fluorescence
      microscopy indicated that the Y270terEYFP protein is expressed in photoreceptors
      and mislocalised within the cell. Immunohistochemical examination of transgenic
      pigs showed photoreceptor loss and disorganised inner and outer segments.
      Electroretinography demonstrated diminished responses in both transgenic models.
      CONCLUSIONS: These transgenic pigs provide unique animal models for examining
      macular degeneration and STGD3 pathogenesis.

PMID- 21873317
TI  - Scleral calcification.

PMID- 21873316
TI  - Supraciliary shunt in refractory glaucoma.
AB  - AIMS: This study aimed to evaluate the efficacy of Gold Micro Shunt (GMS) for
      suprachoroidal drainage in patients with refractory glaucoma. METHODS: This is a
      prospective uncontrolled case series study. Fifty-five eyes of 55 patients were
      included. Study eyes underwent GMS implantation in the supraciliary space. Follow
      up visits were performed on day 1, week 1 and months 1, 3, 6, 12 and 24; patients
      underwent slit-lamp examination, Goldmann applanation tonometry, ultrasound
      biomicroscopy and gonioscopy. RESULTS: Before inclusion, the eyes underwent an
      average (+/- SD) of 1.9 +/- 0.7 (range 1-5) previous glaucoma surgery procedures.
      Forty eyes were pseudophakic, 12 were phakic and 3 were aphakic. The mean
      baseline intraocular pressure was 30.8 +/- 8.8 mm Hg (range 22-58 mm Hg) despite
      maximal medical treatment. After 2 years of follow-up, qualified success was
      achieved in 37 eyes (67.3%) and complete success was achieved in 3 eyes (5.5%).
      In success group patients, mean intraocular pressure decreased from 27.6 +/- 6.9
      at baseline to 13.7 +/- 2.98 mm Hg after 2 years of follow-up; the mean (+/- SD)
      number of medications was 1.4 +/- 0.7 in the postoperative phase, compared with a
      value of 2.5 +/- 0.9 in the preoperative phase. Mild side effects occurred in 21
      patients, with mild or moderate postoperative hyphema being the most frequent
      one. Development of a thin membrane, obstructing the anterior holes, was the most
      important factor affecting the efficacy of this device; it was found to be
      present in 12 patients from the failure group (66.7% of failures). CONCLUSION:
      GMS achieved qualified success in about 67.3% of eyes with uncontrolled
      refractory glaucoma with a low rate of complications.

PMID- 21873318
TI  - Pneumopericardium: diagnosing a rare entity with bedside imaging.

PMID- 21873319
TI  - Remifentanil use in emergency department patients: initial experience.
AB  - INTRODUCTION: This study examines the use of remifentanil, an ultra-short-acting
      opioid, in emergency department (ED) patients. METHODS: Chart review of ED
      patients receiving remifentanil for procedural sedation in an urban general ED.
      RESULTS: 50 patients over a 28-month period with a mean age of 30.6 years (+/
      2.6) were reviewed. Procedures performed included: abscess drainage (13);
      fracture care (9); thoracostomy (8); lumbar puncture (7); shoulder reduction (3);
      cardioversion (3) and others (7). Six (12%) cases received additional rescue
      medications. All procedures were successfully completed in the ED. No
      complications were recorded but 21 (42%) were admitted for underlying pathology.
      CONCLUSION: Remifentanil is a safe and effective medication for ED use.

PMID- 21873320
TI  - Recognition of endotracheal tube migration.

PMID- 21873321
TI  - Knowledge of radiation exposure in common radiological investigations: a
      comparison between radiologists and non-radiologists.
AB  - BACKGROUND: Radiological examinations are commonly requested for patients to aid
      clinical diagnosis. However, many doctors do not realise how much radiation
      dosage their patients are exposed to during radiological investigations. This
      study aims to assess and compare the knowledge of radiologists and non
      radiologists about radiation doses of common radiological investigations.
      METHODS: A prospective questionnaire study of doctors about the dosage of
      commonly performed radiological investigations in a university teaching hospital
      in Hong Kong. Participants were asked to indicate the average dose of radiation
      (in mSv) for a standard chest x-ray exposure. Doctors were then asked to estimate
      the doses of radiation (measured in chest x-ray equivalents) for various
      radiological procedures. The results of radiologists and non-radiologists were
      compared. RESULTS: 158 doctors (25 radiologists and 133 non-radiologists)
      completed the questionnaire. The overall accuracy was 40% for radiologists and
      16% for non-radiologists. One-third of non-radiologists could not distinguish
      radiological examinations with or without ionising radiation. No non-radiologists
      correctly stated the radiation dose (in mSv) of a conventional chest x-ray, and
      77% underestimated the dose of radiological examinations. For radiologists, only
      32% were correct for the radiation dose of a conventional chest x-ray while 7%
      underestimated the radiation doses. CONCLUSION: Knowledge of radiation doses of
      investigation is generally inadequate among radiologists, and particularly poor
      in non-radiologists. Underestimation of radiation doses may expose patients to
      increasing radiological investigation and exposure to radiation hazards.
      Awareness of the radiation hazard of radiological examinations should be raised
      among medical professionals.

PMID- 21873322
TI  - Smoking in movies and adolescent smoking: cross-cultural study in six European
      countries.
AB  - AIM: To investigate whether the association between exposure to smoking in movies
      and smoking among youth is independent of cultural context. METHOD: Cross
      sectional survey of 16,551 pupils recruited in Germany, Iceland, Italy, the
      Netherlands, Poland and Scotland with a mean age of 13.4 years (SD=1.18) and an
      equal gender distribution. School-based surveys were conducted between November
      2009 and June 2010. Using previously validated methods, exposure to movie smoking
      was estimated from the 250 top-grossing movies of each country (years 2004-2009)
      and related to ever smoking. RESULTS: Overall, 29% of the sample had tried
      smoking. The sample quartile (Q) of movie smoking exposure was significantly
      associated with the prevalence of ever smoking: 14% of adolescents in Q1 had
      tried smoking, 21% in Q2, 29% in Q3 and 36% in Q4. After controlling for age,
      gender, family affluence, school performance, television screen time, number of
      movies seen, sensation seeking and rebelliousness and smoking within the social
      environment (peers, parents and siblings), the adjusted ORs for having tried
      smoking in the entire sample were 1.3 (95% CI 1.1 to 1.5) for adolescents in Q2,
      1.6 (95% CI 1.4 to 1.9) for Q3 and 1.7 (95% CI 1.4 to 2.0) for Q4 compared with
      Q1. The adjusted relationship between ever smoking and higher movie smoking
      exposure levels was significant in all countries with a non-linear association in
      Italy and Poland. CONCLUSIONS: The link between smoking in movies and adolescent
      smoking is robust and transcends different cultural contexts. Limiting young
      people's exposure to movie smoking could have important public health
      implications.

PMID- 21873323
TI  - I have taken my umbrella, so of course it does not rain.
AB  - Spirometry is used worldwide to diagnose respiratory disease, and it is a
      validated measure to assess airway obstruction. Irreversible airway obstruction
      is the defining feature of chronic obstructive pulmonary disease (COPD). Thus, an
      FEV(1)/FVC ratio <70% is used to diagnose COPD, and the severity is thereafter
      based on the level of FEV(1). This definition is widely used in clinical practice
      and research, yet may lead to confusion with respect to the diagnosis associated
      with the presence of airway obstruction. The three main reasons are the
      following: (1) fixed airflow obstruction may be the result of specific diagnoses
      such as cystic fibrosis; (2) FEV(1)/FVC ratio changes with ageing, and it is
      therefore inappropriate to use the same ratio at 40 and 90 years, leaving aside
      gender differences; (3) even when specific diagnoses are excluded, fixed airflow
      obstruction may be the end-stage of many different underlying processes. The
      authors believe that they have strong arguments that a COPD diagnosis based
      solely on spirometric values is nonsense. More sophisticated lung function tests,
      such as plethysmography, forced oscillation and lung clearance index, may help
      further to delineate the characteristics of low lung function. However, these are
      not feasible in most clinical contexts and in epidemiologic studies. Therefore,
      the authors throw down the gauntlet: spirometry is an essential tool in patient
      evaluation but dangerous for disease diagnosis, and the term COPD should only be
      used in the appropriate clinical (diagnostic) context.

PMID- 21873324
TI  - Progressive static pulmonary hyperinflation in survivors of severe
      bronchopulmonary dysplasia by mid-adulthood.
AB  - BACKGROUND: Severe bronchopulmonary dysplasia (BPD) might be associated with an
      accelerated age-related decline of lung function. METHODS: 14 individuals were
      studied longitudinally at 15+/-4, 18+/-3 and 38+/-3.2 years. Information on
      personal history was completed, and lung function testing and skin prick testing
      were performed. Longitudinal data were compared intra-individually and with
      matched controls from the NHANES III dataset. RESULTS: The ratio of residual
      volume/total lung capacity (RV/TLC) increased markedly from 25.9+/-7.0% to 39.3+/
      6.8%. A significant time-effect was found compared to controls for the forced
      vital capacity (FVC) which decreased more rapidly than expected. Flow values were
      at the lower limit of normal range but remained relatively stable over time. Some
      individuals had completely normal lung function results. CONCLUSION: Increasing
      static pulmonary hyperinflation with age is indicative of bronchiolar dysfunction
      or early emphysematous changes in survivors of severe BPD. Susceptibility for
      long-term sequelae shows significant variability.

PMID- 21873325
TI  - Recent clinical history and cognitive dysfunction for attention and executive
      function among human immunodeficiency virus-infected patients.
AB  - This study examined the association between recent trends in CD4 and viral loads
      and cognitive test performance with the expectation that recent history could
      predict cognitive performance. Eighty-three human immunodeficiency virus (HIV)
      infected patients with a mean CD4 count of 428 copies/ml were examined in this
      study (62% with undetectable plasma viral load [PVL]). We investigated the
      relationships between nadir CD4 cell count, 1-year trends in immunologic
      function/PVLs, and cognitive performance across several domains using linear
      regression models. Nadir CD4 cell count was predictive of current executive
      function (p = .004). One year clinical history for CD4 cell counts and/or PVLs
      were predictive of executive function, attention/working memory, and
      learning/memory measures (p < .05). Models that combined recent clinical history
      trends and nadir CD4 cell counts suggested that recent clinical trends were more
      important in predicting current cognitive performance for all domains except
      executive function. This research suggests that recent CD4 and viral load history
      is an important predictor of current cognitive function across several cognitive
      domains. If validated, clinical variables and cognitive dysfunction models may
      improve our understanding of the dynamic relationships between disease evolution
      and progression and CNS involvement.

PMID- 21873326
TI  - Utility of the mild brain injury atypical symptoms scale as a screening measure
      for symptom over-reporting in operation enduring freedom/operation iraqi freedom
      service members with post-concussive complaints.
AB  - Evaluation of post-deployment conditions such as post-concussive syndrome (PCS)
      and posttraumatic stress disorder (PTSD) frequently relies upon brief, self
      report checklists which are face valid and highly susceptible to potential
      symptom validity issues such as symptom exaggeration. We investigated the
      psychometric prope1rties of a 5-item measure of symptom exaggeration (mild brain
      injury atypical symptoms [mBIAS] scale) embedded in commonly used PCS and PTSD
      screening instruments in a sample of 403 patients seen in a brain injury clinic
      at a large military medical center. Exploratory factor analysis, examining
      measures of posttraumatic stress, post-concussive symptoms, and symptom over
      reporting revealed a 6-factor model with the mBIAS scale items representing a
      unique factor. Analysis of psychometric properties demonstrated that a score of 8
      on the mBIAS was optimal for the detection of symptom over-reporting (sensitivity
      = 0.94, specificity = 0.92) and appears to be the most favorable cut score for
      interpretive use. The findings provide a strong initial support for the use of
      the mBIAS in post-deployment populations.

PMID- 21873327
TI  - Finding recurrent copy number alterations preserving within-sample homogeneity.
AB  - MOTIVATION: Copy number alterations (CNAs) represent an important component of
      genetic variation and play a significant role in many human diseases. Development
      of array comparative genomic hybridization (aCGH) technology has made it possible
      to identify CNAs. Identification of recurrent CNAs represents the first
      fundamental step to provide a list of genomic regions which form the basis for
      further biological investigations. The main problem in recurrent CNAs discovery
      is related to the need to distinguish between functional changes and random
      events without pathological relevance. Within-sample homogeneity represents a
      common feature of copy number profile in cancer, so it can be used as additional
      source of information to increase the accuracy of the results. Although several
      algorithms aimed at the identification of recurrent CNAs have been proposed, no
      attempt of a comprehensive comparison of different approaches has yet been
      published. RESULTS: We propose a new approach, called Genomic Analysis of
      Important Alterations (GAIA), to find recurrent CNAs where a statistical
      hypothesis framework is extended to take into account within-sample homogeneity.
      Statistical significance and within-sample homogeneity are combined into an
      iterative procedure to extract the regions that likely are involved in functional
      changes. Results show that GAIA represents a valid alternative to other proposed
      approaches. In addition, we perform an accurate comparison by using two real aCGH
      datasets and a carefully planned simulation study. AVAILABILITY: GAIA has been
      implemented as R/Bioconductor package. It can be downloaded from the following
      page http://bioinformatics.biogem.it/download/gaia. CONTACT:
      ceccarelli@unisannio.it; morganella@unisannio.it. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 21873328
TI  - Effective prediction of response to cardiac resynchronization therapy using a
      novel program of gated myocardial perfusion single photon emission computed
      tomography.
AB  - AIMS: The limitation of QRS duration as a surrogate measure for left ventricular
      (LV) mechanical dyssynchrony (LVMD) in cardiac resynchronization therapy (CRT)
      patient selection encourages seeking alternatives to QRS duration. Exploring the
      potential of an analysis program of electrocardiographically gated myocardial
      perfusion single photon emission computed tomography (SPECT) (GMPS) for the
      estimation of LVMD to predict CRT response. METHODS AND RESULTS: Twenty-four
      patients undergoing CRT for advanced heart failure caused by non-ischaemic
      cardiomyopathy were studied. Gated myocardial perfusion single photon emission
      computed tomographies were performed in the setting of temporary CRT suspension
      after 1 week of CRT adoption. The GMPS data were computed with a novel program
      capable of segmental LV time-volume analysis. When a brain natriuretic peptide
      (BNP) value decreased >50% at 6-month follow-up, the patient was defined as a CRT
      responder. Receiver operating characteristic (ROC) curves for identification of
      responders were analysed for standard deviation of time to end systole (TES-SD)
      among 17 LV segments. Linear regression analyses demonstrated that an increase in
      percentage reduction in BNP level at 6-month follow-up was predicted by an
      increase in TES-SD (R(2) = 0.21, P = 0.023). The TES-SD in responders (n = 15,
      62.5%) was higher than that in non-responders (100 +/- 51 vs. 41 +/- 17 ms, P =
      0.0008). A cutoff value of TES-SD >49 ms predicted responders with 100%
      sensitivity and 78.8% specificity and the area under the ROC curve was 0.881 for
      TES-SD (P = 0.002). CONCLUSIONS: The estimation of LVMD using this novel GMPS
      program could be an alternative or a complementary approach to QRS duration in
      CRT patient selection. This finding warrants further assessment of our approach
      in larger studies.

PMID- 21873330
TI  - Allocation of absorbed light energy in PSII to thermal dissipations in the
      presence or absence of PsbS subunits of rice.
AB  - The thermal dissipation (TD) of absorbed light energy in PSII is considered to be
      an important photoprotection process in photosynthesis. A major portion of TD has
      been visualized through the analysis of Chl fluorescence as energy quenching (qE)
      which depends on the presence of the PsbS subunit. Although the physiological
      importance of qE-associated TD (qE-TD) has been widely accepted, it is not yet
      clear how much of the absorbed light energy is dissipated through a qE-associated
      mechanism. In this study, the fates of absorbed light energy in PSII with regard
      to different TD processes, including qE-TD, were quantitatively estimated by the
      typical energy allocation models using transgenic rice in which psbS genes were
      silenced by RNA interference (RNAi). The silencing of psbS genes resulted in a
      decrease in the light-inducible portion of TD, whereas the allocation of energy
      to electron transport did not change over a wide range of light intensities. The
      allocation models indicate that the energy allocated to qE-TD under saturating
      light is 30-50%. We also showed that a large portion of absorbed light energy is
      thermally dissipated in manners that are independent of qE. The nature of such
      dissipations is discussed.

PMID- 21873329
TI  - Molecular mechanisms underlying the Arabidopsis circadian clock.
AB  - A wide range of biological processes exhibit circadian rhythm, enabling plants to
      adapt to the environmental day-night cycle. This rhythm is generated by the so
      called 'circadian clock'. Although a number of genetic approaches have identified
      >25 clock-associated genes involved in the Arabidopsis clock mechanism, the
      molecular functions of a large part of these genes are not known. Recent
      comprehensive studies have revealed the molecular functions of several key clock
      associated proteins. This progress has provided mechanistic insights into how key
      clock-associated proteins are integrated, and may help in understanding the
      essence of the clock's molecular mechanisms.

PMID- 21873331
TI  - Inhibition of glycogen synthase kinase 3beta induces dermal fibrosis by
      activation of the canonical Wnt pathway.
AB  - OBJECTIVE: Glycogen synthase kinase 3beta (GSK-3) regulates the phosphorylation
      and subsequent degradation of beta-catenin, thereby preventing aberrant
      activation of the canonical Wnt pathway. A study was undertaken to define the
      role of GSK-3 in fibroblast activation and in experimental models of systemic
      sclerosis (SSc). METHODS: siRNA and specific inhibitors were used to inhibit GSK
      3 in cultured fibroblasts and in mice. Activation of the canonical Wnt signalling
      was analysed by determining the levels of nuclear beta-catenin and by measuring
      the mRNA levels of the Wnt target gene Axin2. The effects of GSK-3 on the release
      of collagen were evaluated in human dermal fibroblasts and in the mouse model of
      bleomycin-induced skin fibrosis in tight-skin-1 (tsk-1) mice. RESULTS: Targeting
      GSK-3 potently activated the canonical Wnt pathway in fibroblasts in vitro and in
      vivo. Inactivation of GSK-3 dose-dependently stimulated the release of collagen
      from cultured fibroblasts in a beta-catenin-dependent manner and further resulted
      in progressive accumulation of collagen and dermal thickening in mice. Inhibition
      of GSK-3 aggravated experimental fibrosis in bleomycin-challenged mice and in tsk
      1 mice. CONCLUSION: Inhibition of GSK-3 activates the canonical Wnt pathway in
      fibroblasts, stimulates the release of collagen from fibroblasts, exacerbates
      experimental fibrosis and is sufficient to induce fibrosis. GSK-3 is therefore a
      key regulator of the canonical Wnt signalling in fibroblasts and inhibition of
      GSK-3 results in fibroblast activation and increased release of collagen.

PMID- 21873332
TI  - Subclinical gut inflammation in spondyloarthritis is associated with a pro
      angiogenic intestinal mucosal phenotype.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF-A) and placental growth
      factor (PlGF) are major regulators of pathological angiogenesis, which is a
      prominent feature of both Crohn's disease (CD) and peripheral synovitis in
      spondyloarthritis. OBJECTIVE: To investigate the presence of VEGF-A and PlGF in
      the gut of spondyloarthritis patients and to link this finding with subclinical
      gut inflammation in these patients. METHODS: Intestinal biopsies from healthy
      controls, CD patients, spondyloarthritis patients with or without subclinical gut
      inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A,
      PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed.
      RESULTS: Spondyloarthritis patients with subclinical gut inflammation had
      markedly increased intestinal VEGF-A expression (p<0.001), mucosal
      vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy
      controls and RA patients, which, unlike in CD patients, was also seen when the
      gut inflammation was in a quiescent state. PlGF expression was highly increased
      in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with
      healthy controls), but not at all in CD. CONCLUSION: A pro-angiogenic intestinal
      phenotype is observed in spondyloarthritis patients with quiescent chronic gut
      inflammation. This favours an environment for enhanced trafficking of immune
      cells in this subpopulation.

PMID- 21873334
TI  - Current state and future directions of autologous hematopoietic stem cell
      transplantation in systemic lupus erythematosus.
AB  - Autologous haematopoietic stem cell transplantation (AHSCT) has been proposed as
      a treatment modality which may arrest the autoimmune disease process and lead to
      sustained treatment-free remissions. Since the first consensus statement in 1997,
      approximately 200 autologous bone marrow or haematopoietic stem cell
      transplantations (HSCTs) have been reported worldwide for systemic lupus
      erythematosus (SLE). The current state of AHSCT in SLE was reviewed at a recent
      meeting of the autoimmune working party of the European Group for Blood and
      Marrow Transplantation. There was general agreement among experts in this field
      that in patients with severe SLE refractory to conventional immunosuppressive
      treatments, AHSCT can achieve sustained clinical remissions (ranging from 50% to
      70% disease-free survival at 5 years) associated with qualitative immunological
      changes not seen with other forms of treatment. However, this clinical benefit is
      associated with an increase in short-term mortality in most studies. Improving
      patient selection, long-term follow-up of patients after AHSCT, optimisation of
      induction and maintenance treatment together with detailed analysis of the immune
      system are identified as key areas for future research. Optimally, AHSCT should
      be compared with conventional treatment in randomised controlled trials.
      Development of stronger transplant registries, defining a core set of clinical
      data and standardising biological sample collections would make future
      collaborations and comparison of studies more feasible.

PMID- 21873333
TI  - Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis
      and associated with pulmonary vascular disease.
AB  - BACKGROUND: Glycosylation represents an important modification that regulates
      biological processes in tissues relevant for disease pathogenesis in systemic
      sclerosis (SSc), including the endothelium and extracellular matrix. Whether
      patients with SSc develop antibodies to carbohydrates is not known. OBJECTIVES:
      To determine the prevalence and clinical phenotype associated with serum IgG
      antibodies recognising distinct glycans in patients with SSc. METHODS: Pooled
      serum samples from patients with SSc and controls were screened for the presence
      of specific anticarbohydrate antibodies using a novel array containing over 300
      glycans. Antibody titres to 4-sulfated N-acetyl-lactosamine (4S-LacNAc,
      (4OSO3)Galbeta1-4GlcNAc) were determined in 181 individual serum samples from
      patients with SSc by ELISA and associated with disease phenotype. RESULTS: 4S
      LacNAc was identified as a target in pooled SSc serum. Anti-4S-LAcNAc antibodies
      were detected in 27/181 patients with SSc (14.9%) compared with 1/40 healthy
      controls (2.5%). Sulfation at position C4 of galactose (4S-LacNAc) was found to
      be critical for immunogenicity. Anti-4S-LacNAc antibody-positive patients with
      SSc had a higher prevalence of pulmonary hypertension by echocardiography than
      anti-4S-LacNAc-negative patients (15/27 (55.7%) vs 49/154 (31.8%), p=0.02) with
      an OR of 2.6 (95% CI 1.1 to 6.3). Anti-4S-LacNAc-positive patients accounted for
      23.4% of all patients with pulmonary hypertension. CONCLUSION: Serum from
      patients with SSc contains IgG antibodies targeting distinct sulfated
      carbohydrates. The presence of anti-4S-LacNAc antibodies is associated with a
      high prevalence of pulmonary hypertension. These results suggest that specific
      post-translational carbohydrate modifications may act as important immunogens in
      SSc and may contribute to disease pathogenesis.

PMID- 21873335
TI  - NDX-1 protein hydrolyzes 8-oxo-7, 8-dihydrodeoxyguanosine-5'-diphosphate to
      sanitize oxidized nucleotides and prevent oxidative stress in Caenorhabditis
      elegans.
AB  - 8-oxo-dGTP is generated in the nucleotide pool by direct oxidation of dGTP or
      phosphorylation of 8-oxo-dGDP. It can be incorporated into DNA during
      replication, which would result in mutagenic consequences. The frequency of
      spontaneous mutations remains low in cells owing to the action of enzymes
      degrading such mutagenic substrates. Escherichia coli MutT and human MTH1
      hydrolyze 8-oxo-dGTP to 8-oxo-dGMP. Human NUDT5 as well as human MTH1 hydrolyze 8
      oxo-dGDP to 8-oxo-dGMP. These enzymes prevent mutations caused by
      misincorporation of 8-oxo-dGTP into DNA. In this study, we identified a novel
      MutT homolog (NDX-1) of Caenorhabditis elegans that hydrolyzes 8-oxo-dGDP to 8
      oxo-dGMP. NDX-1 did not hydrolyze 8-oxo-dGTP, 2-hydroxy-dATP or 2-hydroxy-dADP.
      Expression of NDX-1 significantly reduced spontaneous A:T to C:G transversions
      and mitigated the sensitivity to a superoxide-generating agent, methyl viologen,
      in an E. coli mutT mutant. In C. elegans, RNAi of ndx-1 did not affect the
      lifespan of the worm. However, the sensitivity to methyl viologen and menadione
      bisulfite of the ndx-1-RNAi worms was enhanced compared with that of the control
      worms. These facts indicate that NDX-1 is involved in sanitization of 8-oxo-dGDP
      and plays a critical role in defense against oxidative stress in C. elegans.

PMID- 21873337
TI  - Design and preliminary results of the heart function assessment registry trial in
      Saudi Arabia (HEARTS) in patients with acute and chronic heart failure.
AB  - AIMS: The heart function assessment registry trial in Saudi Arabia (HEARTS) is
      the first multicentre national quality improvement initiative in the Arab
      population to study the clinical features, management, and outcomes of inpatients
      admitted with acute heart failure (AHF) and outpatients with high-risk chronic
      heart failure (HCHF). METHODS AND RESULTS: We conducted a prospective pilot phase
      for the registry that included consecutive patients with AHF and HCHF in five
      tertiary care hospitals in Saudi Arabia between October 2009 and December 2010.
      The study enrolled 1090 patients, 722 (66.2%) of whom were admitted with AHF and
      368 (33.8%) had HCHF. The mean age +/- SD of AHF patients was 60.6 +/- 15.3
      years; 65.2% were men, 55.3% were de novo heart failure, 60.7% had diabetes
      mellitus, 72.5% had moderate or severe left ventricular (LV) systolic
      dysfunction, and 51.5% had coronary artery disease as the main aetiology. More
      than 80% of AHF and HCHF patients were treated with beta-blockers and angiotensin
      converting enzyme inhibitors/angiotensin receptor blockers. Patients with HCHF
      had a similar clinical profile, but only one-third had implantable cardioverter
      defibrillators. In-hospital mortality was 5.3% for AHF patients and 7.5% at 30
      days after hospital discharge. CONCLUSION: Heart failure patients in Saudi Arabia
      present at a relatively younger age, have a much higher rate of diabetes
      mellitus, and predominantly have LV systolic dysfunction, which is mainly
      ischaemic in origin, compared with patients in developed countries. The
      preliminary results of the study show potential targets for improvement in care.

PMID- 21873338
TI  - Cardiac magnetic resonance for early detection and risk stratification of
      patients with non-compaction cardiomyopathy.

PMID- 21873336
TI  - Signalling mechanisms of RhoGTPase regulation by the heterotrimeric G proteins
      G12 and G13.
AB  - G protein-mediated signal transduction can transduce signals from a large variety
      of extracellular stimuli into cells and is the most widely used mechanism for
      cell communication at the membrane. The RhoGTPase family has been well
      established as key regulators of cell growth, differentiation and cell shape
      changes. Among G protein-mediated signal transduction, G12/13-mediated signalling
      is one mechanism to regulate RhoGTPase activity in response to extracellular
      stimuli. The alpha subunits of G12 or G13 have been shown to interact with
      members of the RH domain containing guanine nucleotide exchange factors for Rho
      (RH-RhoGEF) family of proteins to directly connect G protein-mediated signalling
      and RhoGTPase signalling. The G12/13-RH-RhoGEF signalling mechanism is well
      conserved over species and is involved in critical steps for cell physiology and
      disease conditions, including embryonic development, oncogenesis and cancer
      metastasis. In this review, we will summarize current progress on this important
      signalling mechanism.

PMID- 21873339
TI  - The effect of cardiac resynchronization therapy on left ventricular diastolic
      function assessed with speckle-tracking echocardiography.
AB  - AIMS: Changes in left ventricular (LV) diastolic function after cardiac
      resynchronization therapy (CRT) in relation to LV reverse remodelling and heart
      failure aetiology have not been extensively characterized. The aims of the study
      were to evaluate changes in LV diastolic function with speckle-tracking
      echocardiography in relation to: (i) cardiac resynchronization therapy response
      (LV remodelling) and (ii) heart failure aetiology. METHODS AND RESULTS: A total
      of 192 heart failure patients undergoing CRT implantation were evaluated. Speckle
      tracking echocardiography was performed before and 6 months after implantation
      and reliable analysis was obtained in 188 patients. Left ventricular diastolic
      function was assessed by measuring diastolic strain rate during the isovolumic
      relaxation period (SR(IVR)) and by calculating the ratio of peak transmitral E
      wave to SR(IVR) (E/SR(IVR)). Changes in LV diastolic parameters were evaluated in
      responders and non-responders and in patients with ischaemic and non-ischaemic
      cardiomyopathy. Response to CRT was defined as >=15% reduction in LV end-systolic
      volume at 6 months follow-up. One-hundred and nine patients (58%) were defined as
      responders. Significant improvements in LV diastolic performance were observed in
      responders with improvement in SR(IVR) (from 0.14 +/- 0.08 to 0.18 +/- 0.12 s(
      1), P= 0.001) and E/SR(IVR) (from 834 +/- 840 to 641 +/- 612, P= 0.04). In
      addition, LV relaxation improved in patients with non-ischaemic aetiology
      (SR(IVR): from 0.15 +/- 0.08 to 0.19 +/- 0.13 s(-1), P= 0.004). In contrast, LV
      relaxation did not improve in non-responders and in patients with ischaemic heart
      disease. CONCLUSIONS: Novel diastolic strain rate indices are useful for
      evaluating changes in LV diastolic function after CRT. Improvement in diastolic
      function was only observed in responders to CRT and patients with non-ischaemic
      aetiology.

PMID- 21873341
TI  - B-type natriuretic peptide or amino-terminal pro-B-type natriuretic peptide
      guided treatment of heart failure: what is the next STEP?

PMID- 21873342
TI  - A new mechanism preventing proarrhythmia in chronic heart failure: rapid phase
      III repolarization explains the low proarrhythmic potential of amiodarone in
      contrast to sotalol in a model of pacing-induced heart failure.
AB  - AIMS: Life-threatening arrhythmias are a major problem in chronic heart failure
      (CHF). The aim of the present study was to investigate the mechanism underlying
      the low proarrhythmic potential of amiodarone in a model of pacing-induced heart
      failure. METHODS AND RESULTS: Heart failure was induced in 35 female rabbits by
      rapid ventricular pacing, resulting in a significant decrease of ejection
      fraction. Thirty-four rabbits were sham-operated. In 17 of 35 CHF-rabbits and 20
      of 34 'sham'-rabbits, amiodarone (50 mg/kg/day) was fed for 6 weeks. Eight
      monophasic action potentials and a simultaneously recorded 12-lead
      electrocardiogram showed prolongation of QT-interval and action potential
      duration (APD(90)) in all failing hearts (P< 0.05). Amiodarone pre-treatment led
      to a prolongation of APD(90) (+19 ms) as compared with sham-controlled hearts but
      showed only a marginal effect on APD(90) in failing hearts. Infusion of sotalol
      (50-100 uM) led to a significant prolongation of APD(90) in sham and a further
      prolongation of APD(90) in failing hearts [+55 ms (50 uM); +70 ms (100 uM); P<
      0.01 as compared with sham hearts]. Sotalol led to a triangular action potential
      configuration in sham and failing hearts, whereas amiodarone did not cause
      triangularization but caused a rapid phase-III repolarization. Moreover,
      amiodarone did not increase dispersion of repolarization either in sham or in
      failing hearts. Infusion of sotalol led to a significant increase in dispersion
      of repolarization in sham (+29 ms) and a further increase in failing hearts (+67
      ms; P< 0.05). CONCLUSION: Chronic amiodarone results in a rapid phase-III
      repolarization and does not increase dispersion of repolarization. These
      electrophysiological findings are present in healthy hearts and are preserved in
      heart failure. This contributes to the low proarrhythmic potential of amiodarone
      in heart failure.

PMID- 21873344
TI  - Arteriovenous fistula buttonhole cannulation: early experience in an Irish
      haemodialysis unit.

PMID- 21873343
TI  - A critical review of audiological outcome measures for infants and children.
AB  - Outcome evaluation is an important stage in the pediatric hearing aid fitting
      process, however a systematic way of evaluating outcome in the pediatric
      audiology population is lacking. This is in part due to the need for an evidence
      based outcome evaluation guideline for infants and children with hearing loss who
      wear hearing aids. As part of the development of a guideline, a critical review
      of the existing pediatric audiology outcome evaluation tools was conducted.
      Subjective outcome evaluation tools that measure auditory-related behaviors in
      children from birth to 6 years of age were critically appraised using a published
      grading system (Andresen, 2000). Of the tools that exist, 12 were appraised
      because they met initial criteria outlined by the Network of Pediatric
      Audiologists of Canada as being appropriate for children birth to 6 years of age
      who wear hearing aids. Tools that were considered for the guideline scored high
      in both statistical and feasibility criteria. The subjective outcome evaluation
      tools that were ultimately chosen to be included in the guideline were the
      LittlEARS Auditory Questionnaire (Tsiakpini et al., 2004) and the Parents'
      Evaluation of Aural/Oral Performance of Children (PEACH) Rating Scale (Ching &
      Hill, 2005b) due to the high grades they received in the critical review and
      their target age ranges. Following this critical review of pediatric outcome
      evaluation tools, the next step was for the Network Clinicians to evaluate the
      guideline (Moodie et al., 2011b).

PMID- 21873345
TI  - Admission hyperglycemia and TIMI frame count in primary percutaneous coronary
      intervention.
AB  - We evaluated the relationship between admission blood glucose levels and
      estimated coronary flow by the thrombolysis in myocardial infarction (TIMI) frame
      count (TFC) method in patients with ST-segment elevation myocardial infarction
      (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The TFC of
      121 consecutive patients with STEMI were evaluated after pPCI. Patients with
      admission glucose levels > 198 mg/dL (11 mmol/L) were defined as hyperglycemic.
      Hyperglycemia was observed in 36 (29.8%) patients. The TFC was significantly
      higher in patients with hyperglycemia (70.75 [10-96] vs 56.87 [8-100], P = .04).
      No-reflow frequency was higher in the hyperglycemia group (44.4% vs 23.5%, P =
      .02). In multivariate linear regression analysis admission glucose was an
      independent predictor of high TFC (B = 0.21, P = .02). Our findings suggest that
      admission blood glucose is a predictor of TFC which reflects coronary blood flow.

PMID- 21873346
TI  - The role of hyperbaric oxygen in the treatment of diabetic foot ulcers.
AB  - Diabetic foot ulcers are still extremely difficult to heal. Therefore,
      therapeutic options to improve healing rates are continuously being explored.
      Hyperbaric oxygen (HBO) has been used in addition to standard treatment of the
      diabetic foot for more than 20 years. Evidence suggests that HBO reduces
      amputation rates and increases the likelihood of healing in infected diabetic
      foot ulcers, in association with improved tissue oxygenation, resulting in better
      quality of life. Nonetheless, HBO represents an expensive modality, which is only
      available in few centers. Moreover, adverse events necessitate a closer
      investigation of its safety. Finally, it is not entirely clear which patients
      stand to benefit from HBO and how these should be selected. In conclusion, HBO
      appears promising, but more experience is needed before its broad implementation
      in the routine care of the diabetic foot.

PMID- 21873347
TI  - Body mass index and hypertension among Chinese governmental and institutional
      employees in Beijing.
AB  - Body mass index (BMI) and hypertension have been found to be associated in most
      studies of diverse populations; however, little information is available on
      whether the positive relationship is consistent among individuals at work sites.
      A work site-based screening was performed in 30 682 employees with a mean age of
      40.3 years. In crude models, higher BMI quartiles above the lowest quartiles (BMI
      < 20.6 kg/m2) were associated with progressively higher odds ratio (OR) of
      hypertension with an OR of 2.80 (95% confidence interval [CI]: 2.67-2.93) for the
      top quartile (BMI >= 24.6 kg/m2). Similar trends were found in fully adjusted
      models. Moreover, a 1-standard deviation (SD) increase in BMI was associated with
      a 42% significantly higher (95% CI 38-46) risk of hypertension after adjusting
      for other factors. Concordant relationships were revealed in all evaluated
      subgroups, even among those without traditional cardiovascular risk factors.

PMID- 21873348
TI  - Inflammation as a marker for the prediction of internal carotid artery restenosis
      following eversion endarterectomy--evidence from clinical studies.
AB  - The role of inflammation is well established in the pathogenesis of
      atherosclerosis and an increased level of circulating inflammatory markers may
      predict the future risk of atherosclerosis progression and plaque rupture. C
      reactive protein (CRP) identification by hypersensitive methods (high-sensitivity
      CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid
      endarterectomy (CEA) is a well-established procedure for carotid stenosis
      treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis
      reduction may be prevented by the anti-inflammatory effect of statins. This
      review considers the recent findings on the presence of hsCRP and C3 complement
      concentration and inflammatory plaque composition as well as their effects on ICA
      restenosis rate, following eversion CEA with emphasis on human studies.

PMID- 21873349
TI  - Clinical outcomes after endovascular treatment of superficial femoral disease in
      patients with disabling claudication and critical limb ischemia: midterm
      analysis.
AB  - We present the midterm clinical outcomes and predictors of balloon angioplasty
      and stent placement in atherosclerotic femoropopliteal (FP) arterial disease.
      Between January 2002 and August 2006, 155 patients (men = 56%; 71.4 +/- 10.5
      years) underwent 171 FP angioplasty or stent for claudication (n = 82, 54%) or
      critical limb ischemia ([CLI] n = 70, 46%). Follow-up was obtained through
      September 30, 2009. The average follow-up was 3.25 +/- 1.73 years. In claudicants
      versus CLI, the 12-month patency for TransAtlantic InterSociety Consensus II
      (TASC II) classification (TASC A/B) was 93% versus 80%, respectively, and TASC
      C/D 83% versus 80%. At 3 years, TASC A/B was 82% versus 80%, respectively, and
      TASC C/D was 56% versus 80%, respectively. The predictor of clinical failure in
      claudicants was chronic renal insufficiency (CRI) and in CLI, the predictor of
      amputation was hyperlipidemia.

PMID- 21873350
TI  - Predictive values of Framingham risk and coronary artery calcium scores in the
      detection of obstructive CAD in patients with normal SPECT.
AB  - A subgroup of patients with normal stress myocardial perfusion imaging (MPI) have
      obstructive coronary artery disease (CAD) on coronary computed tomographic
      angiography (CCTA). A retrospective study was performed to identify factors
      associated with obstructive CAD in patients with normal MPI. Bivariate
      differences between patients with obstructive (>50% stenosis) and nonobstructive
      (<50% stenosis) CAD were assessed. Of the 105 patients with normal MPI, 42 (40%)
      had obstructive CAD on CCTA. After a multivariable logistic regression analysis
      increased Framingham risk scores ([FRS] >=10%) and coronary artery calcium scores
      ([CACS] >100 Agatston Units [AU]) were independently associated with obstructive
      CAD (P = .006 and P < .0001, respectively). Patients with normal MPI had 13 times
      and 98 times higher odds of having obstructive CAD if they had a FRS >=10% versus
      <10% and CACS >100 AU versus <=100 AU, respectively. Increased FRS and CACS may
      stratify patients who may benefit from further evaluation for significant CAD
      despite normal MPI.

PMID- 21873351
TI  - Arterial ultrasound screening as a tool for coronary risk assessment in
      asymptomatic men and women.
AB  - One of the imaging tests most commonly used to assess cardiovascular diseases
      (CVDs) in daily practice is Doppler ultrasonography of the carotid and femoral
      arteries. We included 2709 participants with no history or symptoms of CVD; they
      had a risk factor assessment and a carotid and femoral ultrasonography at
      baseline. Incident cases of definite coronary events were recorded during a
      median follow-up of 6 years. Approximately, 63% of the sample presented
      abnormalities (carotid stenosis >50%, carotid plaque, femoral plaque, increased
      intima-media thickness [IMT]). A moderately increased IMT (>0.63 mm) or the
      presence of carotid or femoral artery plaque was related to prognosis. The
      associations persisted after adjustment for pretest risk, treatment with statins,
      and other Doppler ultrasonography abnormalities. The hazard ratio increased
      significantly with the number of abnormalities (varying from 2.35 [1.16-4.74] to
      14.83 [6.47-33.9]).

PMID- 21873352
TI  - Increased leisure-time physical activity is associated with lower prevalence of
      the metabolic syndrome in 64-year old women with impaired glucose tolerance.
AB  - The metabolic syndrome (MetS) is characterized by a cluster of factors that
      confer an increased risk of cardiovascular morbidity as well as mortality. It is
      established that physical activity (PA) has a protective role in cardiovascular
      morbidity and mortality, mainly through favorable effects on traditional risk
      factors such as body mass and blood pressure. We assessed the prevalence of MetS
      in a population-based sample of 64-year-old women with impaired glucose tolerance
      (IGT) with respect to leisure-time PA (LTPA). The results showed an inverse
      linear association (P < .05) between LTPA and MetS in this group. In conclusion,
      this study suggests that an increased PA level has an important role in
      preventing MetS in women with IGT.

PMID- 21873353
TI  - WIF1 is a frequent target for epigenetic silencing in squamous cell carcinoma of
      the cervix.
AB  - Aberrant activation of the Wnt/beta-catenin signaling axis is a prominent
      oncogenic mechanism in numerous cancers including cervical cancer. Wnt inhibitory
      factor-1 (WIF1) is a secreted protein that binds Wnt and antagonizes Wnt
      activity. While the WIF1 gene is characterized as a target for epigenetic
      silencing in some tumor types, WIF1 expression has not been examined in human
      cervical tissue and cervical cancer. Here, we show that WIF1 is unmethylated and
      its gene product is expressed in normal cervical epithelium and some cultured
      cervical tumor lines. In contrast, several cervical cancer lines contained dense
      CpG methylation within the WIF1 gene, and expression of both WIF1 transcript and
      protein was restored by culturing cells in the presence of the global DNA
      demethylating agent 5-aza-2'-deoxycytidine. Using single-molecule MAPit
      methylation footprinting, we observed differences in chromatin structure within
      the WIF1 promoter region between cell lines that express and those that do not
      express WIF1, consistent with transcriptional activity and repression,
      respectively. The WIF1 promoter was aberrantly methylated in ~60% (10 of 17) high
      grade highly undifferentiated squamous cell cervical tumors examined, whereas
      paired normal tissue showed significantly lower levels of CpG methylation. WIF1
      protein was not detectable by immunohistochemistry in tumors with quantitatively
      high levels of WIF1 methylation. Of note, WIF1 protein was not detectable in two
      of the seven unmethylated cervical tumors examined, suggesting other mechanisms
      may contribute WIF1 repression. Our findings establish the WIF1 gene as a
      frequent target for epigenetic silencing in squamous cell carcinoma of the
      cervix.

PMID- 21873354
TI  - Assessment of red cell distribution width (RDW) in patients with coronary artery
      ectasia.
AB  - OBJECTIVES: Coronary artery ectasia (CAE) is characterized by an abnormal
      dilatation of the coronary arteries. Red cell distribution width (RDW) is a
      measure of heterogeneity in the size of red blood cell. In this study, we aimed
      to investigate RDW levels in patients with CAE. METHODS: The study population
      included 54 patients with CAE (28 males; mean age, 59 +/- 12) and 40 individuals
      comprising the control group who had normal coronary arteries (17 males; mean
      age, 56 +/- 10). Admission RDW was measured as part of the automated complete
      blood count. RESULTS: The RDW was significantly higher in the CAE group than the
      control (P < .001). Also, high-sensitive C-reactive protein (hs-CRP) levels in
      patients with CAE were significantly higher as compared with controls (P < .001).
      CONCLUSION: This study demonstrates that RDW and hs-CRP were higher in the CAE
      group compared with the control group. These results show that RDW is a reliable,
      simple, and inexpensive marker for patients with CAE.

PMID- 21873355
TI  - Rare and unusual bleeding manifestations in congenital bleeding disorders: an
      annotated review.
AB  - Epistaxis, superficial and deep hematomas, hemarthrosis, gastrointestinal
      bleeding, hematuria represent the most frequent hemorrhagic events in congenital
      coagulation disorders. Occasionally, bleeding manifestations occur in unusual
      sites or are peculiar. A clotting defect may alter the clinical aspect of skin
      conditions or infections (hemorrhagic scabies or varicella). Hemobilia may occur
      as a complication of transjugular liver biopsy in hemophilia or Bernard-Soulier
      syndrome. Hemarthrosis of small joints of feet and hands occur in patients with
      hemophilia treated with protease inhibitors. Intramedullary hematomas of long
      bones have been described in alpha2-plasmin inhibitor or fibrinogen deficiencies.
      Spleen fracture with consequent hemoperitoneum has been reported in patients with
      fibrinogen deficiency. Rectus muscle sheath hematoma may occur in patients with
      factor VII (FVII)or FX deficiency. Acute or subacute intestinal obstruction may
      be caused by intramural wall hematomas in hemophilia and von Willebrand (vW)
      disease. Physicians should always keep in mind that a congenital hemorrhagic
      disorder may cause bleeding in any tissue of the body and therefore alter the
      normal clinical features of a given disease.

PMID- 21873356
TI  - A randomized trial of aprotinin-free fibrin sealant versus absorbable hemostat.
AB  - BACKGROUND: This study evaluated the safety and hemostatic effectiveness of a
      tranexamic acid- and aprotinin-free fibrin sealant versus an absorbable hemostat
      in soft tissue during elective retroperitoneal or intra-abdominal surgery.
      MATERIALS AND METHODS: This randomized, active-controlled, multicenter study
      enrolled patients who were undergoing elective retroperitoneal or intra-abdominal
      surgery and required adjunctive hemostatic measures at the target bleeding site
      (TBS). Patients were randomized (time = 0 minutes) to receive fibrin sealant or
      absorbable hemostat. The primary endpoint was the absence of bleeding at the TBS
      at 10 minutes. Secondary endpoints included the absence of bleeding at 4 and 7
      minutes and the incidence of treatment failure (bleeding at 10 minutes or brisk
      bleeding requiring additional hemostatic measures), and the incidence of
      complications potentially related to bleeding. Adverse events were assessed.
      RESULTS: Patients (N = 124) were randomized to receive fibrin sealant (n = 62) or
      absorbable hemostat (n = 62). A higher percentage of patients who received fibrin
      sealant versus absorbable hemostat achieved hemostasis within 10 minutes (95.2%
      vs 82.3%; 95% CI, 1.02-1.35) and also at 4 (74.2% vs 54.8%; 95% CI, 1.04-1.80)
      and 7 (90.3% vs 77.4%; 95% CI, 1.00-1.39) minutes. A lower incidence of treatment
      failure was observed for patients receiving fibrin sealant. Similar incidences of
      adverse events and complications potentially related to bleeding were observed.
      CONCLUSIONS: This tranexamic acid- and aprotinin-free fibrin sealant is safe and
      effective for achieving hemostasis in soft tissue during elective retroperitoneal
      or intra-abdominal surgery.

PMID- 21873357
TI  - Inherited prothrombotic risk factors in Turkish children with acute lymphoblastic
      leukemia: significance of concomitant genetic mutation.
AB  - Our study was designed to prospectively evaluate the role of the
      methylenetetrahydrofolate reductase (MTHFR) TT677 genotype, the prothrombin (PT)
      620210A mutation, the factor V G1691A mutation in leukemic Turkish children
      treated according to modified BFM 95 study protocols with respect to the onset at
      thromboembolic events. Eighty-two consecutive leukemic children investigated had
      are established inherited prothrombotic risk factor: 29 children showed the MTHFR
      genotype (heterozygous, n = 22; homozygous, n = 7); 3 showed the heterozygous PT
      G20210A variant; 16 were carriers of the factor V mutation (heterozygous). In
      addition, combined prothrombotic defects were found in a further 11 patients the
      MTHFR mutation was combined with the F V mutation (n = 7), the PT G20210A variant
      (n = 2). In 7 (8.5%) of these 82 patients, venous thromboembolism occurred. In
      conclusion, the presence of inherited thrombophilia with Turkish children treated
      acute lymphoblastic leukemia may be useful for designing targeted primary
      prevention strategies.

PMID- 21873358
TI  - Hospital budget implications of substituting dabigatran for warfarin in an
      anticoagulation service.
AB  - The aim of our study was to assess hospital budget implications of substituting
      dabigatran for warfarin in patients enrolled in a large anticoagulation service.
      The study population was identified using criteria from randomized controlled
      trials of dabigatran. We obtained labor costs ($483 per patient) from the
      hospital's anticoagulation service budget, laboratory costs of international
      normalized ratio (INR) tests ($267 per patient), and wholesale costs of warfarin
      5 mg tablets ($31 per patient) and dabigatran 150 mg capsules ($2464 per
      patient). A total of 1774 (93.5%) of 1898 patients were eligible to substitute
      dabigatran for warfarin. The annual projected hospital expense for
      anticoagulation with dabigatran was $4,371,136, attributable to drug cost alone.
      The annual projected cost of warfarin management was $1,385,494. This was
      comprised of $856,842 for labor, $473,658 for INR testing, and $54,994 for the
      drug cost of warfarin. Substitution will result in increased expense due to drug
      cost.

PMID- 21873359
TI  - Ancillary findings on CT pulmonary angiograms and abnormalities on chest
      radiographs in patients in whom pulmonary embolism was excluded.
AB  - To determine whether chest radiographs identify some abnormalities not shown as
      ancillary findings on computed tomography(CT) pulmonary angiograms of patients in
      whom pulmonary embolism (PE) was excluded. This was a retrospective study of
      reports of negative 64-detector CT pulmonary angiograms and chest radiographs.
      Among 332 patients with no PE, pulmonary parenchymal disease was shown in 60
      (18%) only on standard chest radiographs, and pleural or pericardial disease was
      shown in 17 (5%) only on chest radiographs. Skeletal abnormalities were reported
      more frequently on standard chest radiographs, lymph nodes more frequently on CT
      angiograms. Some abnormalities on chest radiographs of patients in whom PE is
      excluded may not be described as ancillary findings on CT pulmonary angiograms.
      This suggests a need for ancillary findings on CT pulmonary angiograms to be
      described systematically. At present, however, plain chest radiographs in some
      patients show ancillary findings not reported on CT angiograms. [corrected].

PMID- 21873360
TI  - Recurrent life-threatening deep tissue hematomas after switching to generic
      enoxaparin: a report and perspective on the approval process for biological
      compounds.
AB  - In the United States, the Food and Drug Administration (FDA) has allowed makers
      of biologic therapies to use the abbreviated new drug application, which does not
      require safety and efficacy studies. Instead this relies on proving equivalency
      with the original compound and demonstrating in vitro activity and similar
      pharmacodynamics. In the United States, a low-molecular-weight heparin,
      enoxaparin, was recently approved in a generic format through the abbreviated new
      drug application. We present a patient treated with branded enoxaparin for 4
      years with no complications. After the switch to the generic enoxaparin, the
      patient developed 2 life-threatening hemorrhages within 4 months of the
      initiation of the compound. This case suggests that the FDA should follow the
      European Medicine Administration (EMA) guidance by tightening its approval
      process for generic bioequivalents and requiring studies demonstrating similar
      safety and efficacy as the parent compound, prior to approval of a generic
      biologically active compound.

PMID- 21873361
TI  - Overt and mild subclinical hypothyroidism do not influence mean platelet volume
      in premenopausal women having low cardiac risk.
AB  - Mean platelet volume (MPV) was studied in subclinical hypothyroidism (SH) and the
      results are conflicting. The aim of this study is to assess how MPV is affected
      in overt hypothyroidism (OH) and mild SH, the 2 end points of hypothyroidism, in
      patients having low cardiac risk. Premenopausal women without any cardiac risk,
      18 with OH, 30 with mild SH, and 37 euthyroid controls were enrolled. Overt
      hypothyroidism group had higher low-density lipoprotein cholesterol (LDL-C) and
      total cholesterol levels than the control group (P < .001 and P < .05,
      respectively). Increase in MPV was insignificant in OH group when compared with
      SH and control groups. No correlation was observed between MPV and metabolic and
      hormonal parameters. Both OH and SH did not influence MPV and high-sensitivity C
      reactive protein (hs-CRP) in patients with low cardiovascular risk, but these
      findings need to be further evaluated in this patient group.

PMID- 21873362
TI  - Upregulation of inflammatory mediators in end-stage renal disease as measured
      using biochip array technology.
AB  - Systemic vascular changes contribute to both the pathogenesis and thrombotic
      comorbidities of end-stage renal disease (ESRD). This study aims to profile
      various biomarkers and better understand their role in the pathogenesis of ESRD.
      Plasma samples from 49 patients with ESRD and 56 control individuals were
      analyzed for markers for inflammation, specifically C-reactive protein (CRP),
      tumor necrosis factor receptor 1 (TNFR1), neutrophil gelatinase-associated
      lipocalin (NGAL); thrombomodulin (TM); neuron-specific enolase (NSE), and
      thrombosis-D-dimer (DD). Compared to controls, all markers studied showed a
      statistically significant upregulation in patients with ESRD. These results
      indicate a polypathologic process in patients with ESRD, leading to
      cardiovascular and cerebrovascular events. However, the clinical significance of
      previously untested markers, such as TNFR1, NGAL, and NSE, still needs to be
      further explored. This study further validates the role of endothelial damage and
      endogenous thrombotic processes in ESRD as evidenced by the increased levels of
      TM and DD.

PMID- 21873363
TI  - Characterization of in vitro hemostatic peptide effects by thromboelastography.
AB  - In this study, we validated a thromboelastography (TEG) method to evaluate the
      hemostatic effects of 3 peptides. The first peptide is an ideal amphipathic
      peptide composed of 22 leucine and lysine in a ratio of 2:1. At a very low
      concentration, the peptide had a procoagulant effect shown by decreases in
      reaction time (R) and coagulation time (K) but was impaired by a decrease in
      maximum amplitude (MA). At higher concentrations, the peptide had an
      anticoagulant effect. The alpha angle was minimally affected by the peptide. The
      second peptide is melittin derived from bee venom. Melittin showed procoagulant
      effects reflected by a decrease in clotting time but led to lower MA. The third
      peptide derived from fibrinogen gamma chain promoted hemostasis only at an
      optimal concentration and became anticoagulant at a higher concentration. The
      hemostatic mechanisms of each peptide were discussed. Our study would facilitate
      further development of peptides for either hemorrhage control or thrombosis
      treatment.

PMID- 21873364
TI  - Vascularized rib support for chest wall reconstruction using Gore-Tex dual mesh
      after wide sternochondral resection.
AB  - Only a few reports describe chest wall reconstruction after sternal resection
      using Gore-Tex dual mesh, and very few reports describe the use of a vascularized
      rib to support the thoracic cage. We present a case of a breast cancer patient
      who underwent anterior chest wall resection for recurrent sternal cancer. Her
      sternoclavicular joints bilaterally and lower sternum were divided using an
      electric saw. The bony chest wall was reconstructed using Gore-Tex dual mesh, and
      a vascularized rib was used to bridge the space between the clavicular heads to
      support the thoracic cage. The patient's postoperative course was uneventful,
      without complications, such as paradoxical respiration or pneumonia.

PMID- 21873365
TI  - Complete transposition of carotid bifurcation: can it be an additional risk
      factor of injury to the cranial nerves during carotid endarterectomy?
AB  - The internal carotid artery (ICA) usually, lies posterolaterally to the external
      carotid artery (ECA). Sometimes a complete carotid transposition can occur, with
      the ECA in a lateral position and the ICA on the medial side can occur. Our study
      evaluated the significance and impact that this anomaly may have on cranial nerve
      injuries. From January 2008 to November 2010, 296 patients underwent 360
      consecutive primary carotid endarterectomy (CEA) procedures. During carotid
      isolation, we detected an unexpected lateral position of the ECA in 11 cases
      (3.6%). chi(2) analysis and the Student's t-test were used to compare the
      incidence of cranial nerve injuries between the 11 patients with the lateral ECA
      who underwent CEA (group A) and 11 randomized patients with a normal bifurcation
      (group B). Statistical significance was inferred at chi(2)>3.84 and P<0.05. A
      statistical difference in the incidence of superior laryngeal nerve paralysis was
      detected between groups A and B (18.1%, 2/11 in group A vs. 0%, 0/11 in group B;
      chi(2)>3.84; P<0.05). No differences in incidence of injury were detected for the
      other cranial nerves. A very meticulous mobilization of the ECA and ICA is needed
      to perform CEA, but superior laryngeal nerve injury can occur despite the use of
      a safe and meticulous surgical technique.

PMID- 21873366
TI  - Thoracoscopic partial thymectomy for untraceable mediastinal parathyroid
      adenomas.
AB  - Despite accurate preoperative imaging, ectopic mediastinal parathyroid adenomas
      can be difficult to find via a thoracic approach. Considering that - in most
      cases - these adenomas are intrathymic, it can be advisable to directly perform a
      partial thymectomy. We present the cases of three patients who were successfully
      cured using a thoracoscopic partial thymectomy.

PMID- 21873367
TI  - Surgical management of pneumothorax: significance of effective admission or
      communication strategies between the district general hospitals and specialized
      unit.
AB  - A preoperative delay in emergency surgery for spontaneous pneumothorax is
      associated with a poor outcome after surgery and a prolonged hospital stay. To
      reduce preoperative delays, all tertiary referrals from district general
      hospitals to our thoracic surgery unit were processed through a 'clinical
      decisions unit' (CDU). Prior to the establishment of the CDU, these patients were
      added to a waiting list for a surgical bed. This study has reviewed the effect of
      this change in admission policy on the efficiency of treatment for non-elective
      spontaneous pneumothorax. An intergroup comparison (pre-CDU group vs. post-CDU
      group) was made of the following parameters: referral to transfer time, transfer
      to surgery time and length of inpatient stay in the referring and tertiary
      hospitals. There were no significant differences in gender, diagnosis, treatment
      in the referring hospitals, postoperative clinical outcome, or indications for or
      type of surgery. The total length of inpatient stay in the referring and tertiary
      hospitals was significantly reduced for the post-CDU group (12 vs. 15 days;
      P<0.001), which was attributed to the earlier transfer of patients (18 vs. 78
      hours; P<0.001) hours. Allowing surgical access to a traditional medical
      admission unit is therefore, cost-effective and significantly improves the
      efficiency of non-elective pneumothorax surgery.

PMID- 21873368
TI  - On the value of nonremovable reminders for behavior modification: an application
      to nail-biting (onychophagia).
AB  - The authors examined the effectiveness of a novel behavior modification method
      for dysfunctional and impulsive habits, based on nonremovable reminders (NrRs).
      NrRs were implemented by having participants wear nonremovable wristbands
      designated to constantly remind them of their resolution to quit the targeted
      habit (nail-biting). Participants were 80 nail-biters who resolved to quit. The
      NrR approach was contrasted with an aversion-based behavioral modification
      technique. Recovery was assessed after 3 and 6 weeks of treatment and in a 5
      month follow-up. The NrR method was associated with lower drop-out rate and was
      as successful as the aversion-based method altogether. When considering only non
      dropouts, the aversion-based method was more effective. This suggests that the
      use of constantly present reminders broadens the target population that can
      benefit from reminders in the course of behavior modification.

PMID- 21873369
TI  - Detecting false positives in multielement designs: implications for brief
      assessments.
AB  - The authors assessed the extent to which multielement designs produced false
      positives using continuous duration recording (CDR) and interval recording with
      10-s and 1-min interval sizes. Specifically, they created 6,000 graphs with
      multielement designs that varied in the number of data paths, and the number of
      data points per data path, using a random number generator. In Experiment 1, the
      authors visually analyzed the graphs for the occurrence of false positives.
      Results indicated that graphs depicting only two sessions for each condition
      (e.g., a control condition plotted with multiple test conditions) produced the
      highest percentage of false positives for CDR and interval recording with 10-s
      and 1-min intervals. Conversely, graphs with four or five sessions for each
      condition produced the lowest percentage of false positives for each method. In
      Experiment 2, they applied two new rules, which were intended to decrease false
      positives, to each graph that depicted a false positive in Experiment 1. Results
      showed that application of new rules decreased false positives to less than 5%
      for all of the graphs except for those with two data paths and two data points
      per data path. Implications for brief assessments are discussed.

PMID- 21873370
TI  - Randomized controlled trial of intraoperative goal-directed fluid therapy in
      aerobically fit and unfit patients having major colorectal surgery.
AB  - BACKGROUND: Intraoperative fluid therapy regimens using oesophageal Doppler
      monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy,
      GDT) have been associated with a reduction in length of stay (LOS) and
      complication rates after major surgery. We hypothesized that intraoperative GDT
      would reduce the time to surgical readiness for discharge (RfD) of patients
      having major elective colorectal surgery but that this effect might be less
      marked in aerobically fit patients. METHODS: In this double-blinded controlled
      trial, 179 patients undergoing major open or laparoscopic colorectal surgery were
      characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of
      their performance during a cardiopulmonary exercise test. Within these fitness
      strata, patients were randomized to receive a standard fluid regimen with or
      without ODM-guided intraoperative GDT. RESULTS: GDT patients received an average
      of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at
      skin closure were significantly higher in the GDT group than in controls. Times
      to RfD and LOS were longer in GDT than control patients but did not reach
      statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7
      days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs
      4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with
      controls. CONCLUSIONS: Intraoperative SV optimization conferred no additional
      benefit over standard fluid therapy. In an aerobically fit subgroup of patients,
      GDT was associated with detrimental effects on the primary outcome. TRIAL
      REGISTRY: UK NIHR CRN 7285, ISRCTN 14680495.
      http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.

PMID- 21873371
TI  - In situ off-axis electron holography of metal-oxide hetero-interfaces in oxygen
      atmosphere.
AB  - Off-axis electron holography has been extended to in situ observations in gas
      atmospheres. The Yttria-stabilized zirconia (YSZ)-Pt hetero-interface was
      characterized by electron holography at high temperature in a vacuum and in an
      oxygen atmosphere. Analysis of the phase shift profiles revealed high mobility of
      anions in the oxide in the vicinity of the interface in the oxygen atmosphere.
      This would compensate for any increase in the number of oxygen vacancies in YSZ
      through the metal interface.

PMID- 21873372
TI  - Modulation of DNA repair capacity by ataxia telangiectasia mutated gene
      polymorphisms among polycyclic aromatic hydrocarbons-exposed workers.
AB  - The purpose of this study was to address the association between the ataxia
      telangiectasia mutated (ATM) gene polymorphisms and susceptibility to DNA repair
      capacity (DRC) among polycyclic aromatic hydrocarbons (PAHs)-exposed workers.
      Polymorphisms of ATM were genotyped. DRC was determined by comet assay.
      Chromosomal damage was detected by cytokinesis-block micronucleus (CBMN) assay.
      Flow cytometry was used to detect the distributions of cell cycle. Expressions of
      ATM and rH2AX were determined by immunoblotting analysis. Luciferase assays were
      performed to determine the functional difference of ATM promoter region allele.
      Subjects carrying T allele of rs228589 had significantly lower DRC compared with
      those with AA genotype. Subjects carrying G allele of rs652311 had significantly
      lower DRC than those with zero copy number of haplotype CGGT. SH ataxia
      telangiectasia mutated (SHATM) cells had significantly lower DRC than SH green
      fluorescent protein (SHGFP) cells induced by bleomycin and higher CBMN
      frequencies treated by benzo(a)pyrene [B(a)P] than SHGFP cells. After B(a)P
      treatment, a decrease in the percentage of G1 phase cells was observed in SHATM
      cells compared with SHGFP cells, rH2AX expressions were increased in SHATM cells
      and SHGFP cells, but ATM expressions had no change in 16HBE-SHGFP cells and HEK
      SHGFP cells. Luciferase expression was not different between rs228589T and
      rs228589A plasmid constructs. In conclusions, it is suggested that ATM
      polymorphisms are associated with DRC among PAHs-exposed workers and ATM plays
      key roles in repair of chromosomal damage and cell cycle control with the
      treatment of B(a)P.

PMID- 21873373
TI  - Predictive models of prenatal developmental toxicity from ToxCast high-throughput
      screening data.
AB  - Environmental Protection Agency's ToxCast project is profiling the in vitro
      bioactivity of chemicals to assess pathway-level and cell-based signatures that
      correlate with observed in vivo toxicity. We hypothesized that developmental
      toxicity in guideline animal studies captured in the ToxRefDB database would
      correlate with cell-based and cell-free in vitro high-throughput screening (HTS)
      data to reveal meaningful mechanistic relationships and provide models
      identifying chemicals with the potential to cause developmental toxicity. To test
      this hypothesis, we built statistical associations based on HTS and in vivo
      developmental toxicity data from ToxRefDB. Univariate associations were used to
      filter HTS assays based on statistical correlation with distinct in vivo
      endpoint. This revealed 423 total associations with distinctly different patterns
      for rat (301 associations) and rabbit (122 associations) across multiple HTS
      assay platforms. From these associations, linear discriminant analysis with cross
      validation was used to build the models. Species-specific models of predicted
      developmental toxicity revealed strong balanced accuracy (> 70%) and unique
      correlations between assay targets such as transforming growth factor beta,
      retinoic acid receptor, and G-protein-coupled receptor signaling in the rat and
      inflammatory signals, such as interleukins (IL) (IL1a and IL8) and chemokines
      (CCL2), in the rabbit. Species-specific toxicity endpoints were associated with
      one another through common Gene Ontology biological processes, such as cleft
      palate to urogenital defects through placenta and embryonic development. This
      work indicates the utility of HTS assays for developing pathway-level models
      predictive of developmental toxicity.

PMID- 21873374
TI  - Effects of developmental exposure to polychlorinated biphenyls and/or
      polybrominated diphenyl ethers on cochlear function.
AB  - Developmental exposure to polychlorinated biphenyls (PCBs) causes hearing loss
      that may be due to reduced thyroxine during cochlear development. Polybrominated
      diphenyl ethers (PBDEs) are structurally similar to PCBs and reduce thyroxine.
      This study utilized an environmental PCB mixture and a commercial PBDE mixture,
      DE-71, that represents the PBDEs found in humans to assess the potential for
      additive effects of PCBs and PBDEs on cochlear function. Female Long-Evans rats
      were dosed with corn oil vehicle, PCBs (3 or 6 mg/kg), molar equivalent doses of
      PBDEs (5.7 or 11.4 mg/kg), 3 mg/kg PCBs + 5.7 mg/kg PBDEs, or 6 mg/kg PCBs + 11.4
      mg/kg PBDEs throughout gestation and lactation. At weaning, pup blood was taken
      to assess thyroxine concentrations. One male and one female from each litter were
      maintained until adulthood for distortion product otoacoustic emission (DPOAE)
      measurements of cochlear function. DPOAE amplitudes were decreased and thresholds
      were elevated in the 6 mg/kg PCB group. Exposure to PBDEs did not cause DPOAE
      deficits. There was an interactive effect from combined exposure such that the
      individual low doses of PCBs and PBDEs did not result in DPOAE deficits, but the
      two combined produced a deficit similar to that in the high-dose PCB group. Serum
      thyroxine concentrations of all groups were reduced compared with controls, but
      PBDEs produced a less dramatic reduction than PCBs, which could explain the lack
      of DPOAE effects. Importantly, there was evidence that the co-exposure to
      subthreshold doses of PCBs and PBDEs can have an additive effect on cochlear
      function.

PMID- 21873375
TI  - Central inflammation and sickness-like behavior induced by the food contaminant
      deoxynivalenol: a PGE2-independent mechanism.
AB  - Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals,
      has been implicated in mycotoxicoses in both humans and farm animals. Low-dose
      toxicity is characterized by reduced weight gain, diminished nutritional
      efficiency, and immunologic effects. The levels and patterns of human food
      commodity contamination justify that DON consumption constitutes a public health
      issue. DON stability during processing and cooking explains its large presence in
      human food. We characterized here DON intoxication by showing that the toxin
      concomitantly affects feeding behavior, body temperature, and locomotor activity
      after both per os and central administration. Using c-Fos expression mapping, we
      identified the neuronal structures activated in response to DON and observed that
      the pattern of neuronal populations activated by the toxin resembled those
      induced by inflammatory signals. By real-time PCR, we report the first evidences
      for a DON-induced central inflammation, attested by the strong upregulation of
      interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, cyclooxygenase-2,
      and microsomal prostaglandin synthase-1 (mPGES-1) messenger RNA. However,
      silencing prostaglandins E2 signaling pathways using mPGES-1 knockout mice, which
      are resistant to cytokine-induced sickness behavior, did not modify the responses
      to the toxin. These results reveal that, despite strong similarities, behavioral
      changes observed after DON intoxication differ from classical sickness behavior
      evoked by inflammatory cytokines.

PMID- 21873376
TI  - Prolonging the past counteracts the pull of the present: protracted speciation
      can explain observed slowdowns in diversification.
AB  - Phylogenetic trees show a remarkable slowdown in the increase of number of
      lineages towards the present, a phenomenon which cannot be explained by the
      standard birth-death model of diversification with constant speciation and
      extinction rates. The birth-death model instead predicts a constant or
      accelerating increase in the number of lineages, which has been called the pull
      of the present. The observed slowdown has been attributed to nonconstancy of the
      speciation and extinction rates due to some form of diversity dependence (i.e.,
      species-level density dependence), but the mechanisms underlying this are still
      unclear. Here, we propose an alternative explanation based on the simple concept
      that speciation takes time to complete. We show that this idea of "protracted"
      speciation can be incorporated in the standard birth-death model of
      diversification. The protracted birth-death model predicts a realistic slowdown
      in the rate of increase of number of lineages in the phylogeny and provides a
      compelling fit to four bird phylogenies with realistic parameter values. Thus,
      the effect of recognizing the generally accepted fact that speciation is not an
      instantaneous event is significant; even if it cannot account for all the
      observed patterns, it certainly contributes substantially and should therefore be
      incorporated into future studies.

PMID- 21873377
TI  - Generalized mixture models for molecular phylogenetic estimation.
AB  - The rapidly growing availability of multigene sequence data during the past
      decade has enabled phylogeny estimation at phylogenomic scales. However, dealing
      with evolutionary process heterogeneity across the genome becomes increasingly
      challenging. Here we develop a mixture model approach that uses reversible jump
      Markov chain Monte Carlo (MCMC) estimation to permit as many distinct models as
      the data require. Each additional model considered may be a fully parametrized
      general time-reversible model or any of its special cases. Furthermore, we expand
      the usual proposal mechanisms for topology changes to permit hard polytomies
      (i.e., zero-length internal branches). This new approach is implemented in the
      Crux software toolkit. We demonstrate the feasibility of using reversible jump
      MCMC on mixture models by reexamining a well-known 44-taxon mammalian data set
      comprising 22 concatenated genes. We are able to reproduce the results of the
      original analysis (with respect to bipartition support) when we make identical
      assumptions, but when we allow for polytomies and/or use data-driven mixture
      model estimation, we infer much lower bipartition support values for several key
      bipartitions.

PMID- 21873378
TI  - Numerous risk factors for Helicobacter pylori antibiotic resistance revealed by
      extended anamnesis: a Bulgarian study.
AB  - The aim of this study was to assess risk factors for primary Helicobacter pylori
      antibiotic resistance by an extended anamnesis. In total, 519 H. pylori strains
      from untreated symptomatic adults who answered a questionnaire were evaluated.
      Strain susceptibility was assessed by a breakpoint susceptibility test. Primary
      resistance rates were 29.5 % for metronidazole, 17.9 % for clarithromycin, 7.3 %
      for metronidazole+clarithromycin, 4.0 % for tetracycline and 10.8 % for
      ciprofloxacin. On multivariate analysis, younger (<=65 years) age was an
      independent predictor for metronidazole resistance. To our knowledge, for the
      first time, being a member of the health-care profession was revealed as a risk
      factor for H. pylori resistance to metronidazole and both metronidazole and
      clarithromycin. Respiratory and urinary tract infections were independent
      predictors of clarithromycin and ciprofloxacin resistance, respectively. The
      presence of co-infections was an independent risk factor for clarithromycin,
      metronidazole and ciprofloxacin resistance. Surprisingly, female sex was the only
      predictor for tetracycline resistance. The antibiotic resistance rates were not
      associated with disease type, place of residence, birthplace, educational level,
      non-steroidal anti-inflammatory drug or proton pump inhibitor use, smoking or
      dietary factors, such as consumption of coffee, yogurt, green tea, raw garlic,
      raw onion, honey or meat. There was a trend for higher metronidazole resistance
      in strains from diabetic patients. In conclusion, the extended anamnesis of H.
      pylori-positive patients should include data on patient age, sex, whether they
      are in the health-care profession, co-infections and possibly diabetes to improve
      the choice of empiric therapy. Tailored treatment based on the extended anamnesis
      is suggested, and susceptibility testing of the strains is recommended for
      patients at risk for antibiotic resistance, especially to clarithromycin,
      fluoroquinolones or both metronidazole and clarithromycin.

PMID- 21873379
TI  - Characterization of highly antimicrobial-resistant clinical pneumococcal isolates
      recovered in a Chinese hospital during 2009-2010.
AB  - Ninety-one consecutive pneumococcal isolates (primarily from sputum), recovered
      in Chongqing Southwest Hospital during a 12 month period in 2009-2010 from
      individuals of all ages with suspected cases of pneumococcal disease, were
      subjected to PCR-serotyping, Quellung reaction serotyping, antimicrobial
      susceptibility testing and multilocus sequence typing (MLST). Although 20
      different serotypes were observed, most isolates (69, 75.8 %) were of serotypes
      included in the pneumococcal 13-valent conjugate vaccine (PCV13), including 33 of
      the 46 (71.7 %) isolates recovered from individuals less than 5 years of age. The
      prevalent serotypes were 19F (34 %), 19A (9.9 %), 6B (9.9 %), 23F (7.7 %), 14
      (6.6 %) and 6A (4.4 %). PCR-determined serotypes were in agreement with Quellung
      testing, with the exception of two serotype 33C isolates. Most or all isolates
      within each PCV13 serotype were represented by one genotype, with the globally
      disseminated MLST sequence types (STs) ST271, ST320, ST90 and ST81 each
      accounting for the highly resistant isolates within serotypes 19F, 19A, 6B and
      23F, respectively. Sixty-six (72.5 %) isolates were resistant to combinations of
      beta-lactam antibiotics (BLAs). A total of 63 of these 66 (95.5 %) BLA-resistant
      isolates were of serotypes included in PCV13; however, 3 serogroup 15 isolates
      were also BLA-resistant. Most isolates (88/91 = 96.7 %) were resistant to
      erythromycin and clindamycin. The majority of isolates were also resistant to
      tetracycline (76, 84 %) and to cotrimoxazole (67, 74 %). This work revealed that
      the majority of antimicrobial-resistant isolates (50/91 = 54.9 %) recovered in
      this Chinese hospital were represented by four global clones. Serotypes for these
      as well as more obscure strains were readily determined by using PCR.

PMID- 21873380
TI  - Emergence and clonal dissemination of carbapenem-hydrolysing OXA-58-producing
      Acinetobacter baumannii isolates in Bolivia.
AB  - Acinetobacter baumannii is an emerging multidrug-resistant pathogen and very
      little information is available regarding its imipenem resistance in Latin
      American countries such as Bolivia. This study investigated the antimicrobial
      resistance profile of 46 clinical strains from different hospitals in Cochabamba,
      Bolivia, from March 2008 to July 2009, and the presence of carbapenemases as a
      mechanism of resistance to imipenem. Isolates were obtained from 46 patients (one
      isolate per patient; 30 males,16 females) with an age range of 1 day to 84 years,
      and were collected from different sample types, the majority from respiratory
      tract infections (17) and wounds (13). Resistance to imipenem was detected in 15
      isolates collected from different hospitals of the city. These isolates grouped
      into the same genotype, named A, and were resistant to all antibiotics tested
      including imipenem, with susceptibility only to colistin. Experiments to detect
      carbapenemases revealed the presence of the OXA-58 carbapenemase. Further
      analysis revealed the location of the bla(OXA-58) gene on a 40 kb plasmid. To our
      knowledge, this is the first report of carbapenem resistance in A. baumannii
      isolates from Bolivia that is conferred by the OXA-58 carbapenemase. The presence
      of this gene in a multidrug-resistant clone and its location within a plasmid is
      of great concern with regard to the spread of carbapenem-resistant A. baumannii
      in the hospital environment in Bolivia.

PMID- 21873381
TI  - Identification of bacteria and potential sources in neonates at risk of infection
      delivered by Caesarean and vaginal birth.
AB  - Neonatal gastric aspirates (NGA) are routinely screened in UK hospitals to
      investigate fetal/neonatal infections associated with cases of adverse pregnancy
      outcome (APO). The aim of this study was to describe and compare the microbiology
      of NGA from Caesarean and vaginal deliveries using molecular methods, and to
      evaluate other possible clinical and non-clinical variables that may have
      determined the presence of the bacteria in the samples. The value of using NGA
      and molecular methods to investigate potential pathogens associated with the risk
      of early infection was also evaluated. Bacteria were identified by a combined
      molecular approach on the basis of the 16S rRNA gene using both clone analysis
      and denaturing gradient gel electrophoresis. A total of 43 and 34 different
      species were identified in the vaginal (n = 121) and Caesarean (n = 119)
      deliveries, respectively; 26 of the species observed (51 %) were common to both
      modalities, although usually less prevalent in the Caesarean cases. Multivariate
      analysis confirmed an association between infection and prolonged rupture of
      membranes in vaginal deliveries (odds ratio = 5.7, 95 % confidence interval = 1.1
      29.0). Various associations between infection and given variables were also
      shown, including labour, intrapartum antibiotic prophylaxis, and time and place
      of sample collection. The molecular methods allowed identification of a range of
      bacteria and potential sources not previously observed in NGA, including possible
      genito-urinary, gastrointestinal and oral pathogens. NGA represents a valuable
      sample for investigating potential pathogens associated with APO and the risk of
      early infection in neonates using molecular methods.

PMID- 21873382
TI  - Chromosomal cephalosporinase in Enterobacter hormaechei as an ancestor of ACT-1
      plasmid-mediated AmpC beta-lactamase.
AB  - In this study of the diversity of AmpC beta-lactamase in clinical isolates of
      Enterobacter spp., a strain was found carrying the plasmid-mediated AmpC beta
      lactamase ACT-1 gene on its chromosome. The strain was identified as Enterobacter
      hormaechei using phylogenetic analysis of 16S rRNA and hsp60 genes. In addition,
      the species was confirmed by DNA-DNA hybridization. The genetic environment of
      the bla(ACT-1) gene was characterized, including the ampR and ampG genes, using a
      two-step PCR. The amino acid sequences of AmpR at serine 35, arginine 86, glycine
      102, aspartic acid 135 and tyrosine 264 were conserved. Measurement of the
      transcription level of the bla(ACT-1) gene using real-time quantitative PCR
      showed that it increased 1.98-fold following cefoxitin induction. These results
      suggest that the plasmid-mediated bla(ACT-1) gene originated from the chromosome
      of E. hormaechei.

PMID- 21873383
TI  - The relationship between acculturation factors and symptoms of depression: a
      cross-sectional study with immigrants living in Athens.
AB  - The process of acculturation observed in immigrants is part of an adjustment to
      the values and norms of a new society, and possibly the loss of norms of the
      society of origin. Acculturation has been linked to stress-related psychological
      disorders such as depression. The present study investigates the relationship
      between three acculturation domains (everyday life behaviors, wishful
      orientation/nostos, and ethnic identity) and symptoms of depression in a sample
      of foreign immigrants living in Athens, Greece. The sample consisted of 317
      immigrants who visited two non-governmental organization polyclinics. All
      participants were interviewed using the Immigrant Acculturation Scale (IAS) and
      the Center for Epidemiological Studies Depression Scale (CES-D). The results
      showed that 133 (42%) out of the 317 interviewees were in a depressive state (CES
      D > 15). The main finding was that high CES-D scores were related to low scores
      in the IAS Everyday Life and Wishful Orientation factors, while no relationship
      was found between depressive symptomatology and the IAS Identity factor. Short
      duration of stay in Greece, lack of steady job, and lack of residence permit were
      also related to high CES-D scores. In conclusion, adaptation to mainstream
      culture daily behaviors as well as the wish to integrate with individuals from
      the mainstream culture and settle permanently in the new country could be seen as
      part of an adaptive mechanism that protects the individual from experiencing
      depressive symptomatology.

PMID- 21873384
TI  - CAWC considers issues surrounding rehoming companion animals.

PMID- 21873387
TI  - AHVLA to set out its proposals on tendering for TB testing.

PMID- 21873389
TI  - 'No excuse' for delaying use of new toxicity test, says RSPCA.

PMID- 21873390
TI  - Defra statistics indicate increased incidence of bovine TB.

PMID- 21873391
TI  - Scotland obtains some leeway on EID for sheep.

PMID- 21873392
TI  - Education: the keystone of the veterinary profession.

PMID- 21873393
TI  - Rational use of medicines.

PMID- 21873394
TI  - Zoonotic transmission of bovine papular stomatitis virus.

PMID- 21873395
TI  - Tendering for TB testing.

PMID- 21873396
TI  - Changing indications for digit amputation in cattle.

PMID- 21873397
TI  - Unusual eggshell defects in a free-range layer flock in Great Britain.

PMID- 21873398
TI  - Providing fair access to veterinary postgraduate education.

PMID- 21873399
TI  - Control of bovine TB in cattle and wildlife.

PMID- 21873400
TI  - One in 10 suicides is among people with a physical illness.

PMID- 21873401
TI  - Japan loans cash to help curb rising incidence of polio in Pakistan.

PMID- 21873402
TI  - Cigarette firms sue regulators over graphic warnings on packs.

PMID- 21873403
TI  - Isoniazid-induced recurrent acute pancreatitis.
AB  - Drug-induced acute pancreatitis should be considered in the differential
      diagnosis of acute abdomen occurring soon after the initiation of antitubercular
      treatment. Isoniazid-induced pancreatitis is potentially reversible: early
      recognition and drug withdrawal are warranted in the appropriate clinical
      setting. We present a case of reversible acute pancreatitis after isoniazid
      treatment of lymph node tuberculosis, followed by the recurrence of pancreatitis
      upon the reintroduction of the drug.

PMID- 21873404
TI  - Structure-function analysis of HsiF, a gp25-like component of the type VI
      secretion system, in Pseudomonas aeruginosa.
AB  - Bacterial pathogens use a range of protein secretion systems to colonize their
      host. One recent addition to this arsenal is the type VI secretion system (T6SS),
      which is found in many Gram-negative bacteria. The T6SS involves 12-15
      components, including a ClpV-like AAA(+) ATPase. Moreover, the VgrG and Hcp
      components have been proposed to form a puncturing device, based on structural
      similarity to the tail spike components gp5/gp27 and the tail tube component gp19
      of the T4 bacteriophage, respectively. Another T6SS component shows similarity to
      a T4 phage protein, namely gp25. The gp25 protein has been proposed to have
      lysozyme activity. Other T6SS components do not exhibit obvious similarity to
      characterized T4 phage components. The genome of Pseudomonas aeruginosa contains
      three T6SS gene clusters. In each cluster a gene encoding a putative member of
      the gp25-like protein family was identified, which we called HsiF. We confirmed
      this similarity by analysing the structure of the P. aeruginosa HsiF proteins
      using secondary and tertiary structure prediction tools. We demonstrated that
      HsiF1 is crucial for the T6SS-dependent secretion of Hcp and VgrG. Importantly,
      lysozyme activity of HsiF proteins was not detectable, and we related this
      observation to the demonstration that HsiF1 localizes to the cytoplasm of P.
      aeruginosa. Finally, our data showed that a conserved glutamate, predicted to be
      required for proper HsiF folding, is essential for its function. In conclusion,
      our data confirm the central role of HsiF in the T6SS mechanism, provide
      information on the predicted HsiF structure, and call for reconsideration of the
      function of gp25-like proteins.

PMID- 21873405
TI  - Analysis of two-component sensor proteins involved in the response to acid
      stimuli in Streptococcus pyogenes.
AB  - The virulence of Streptococcus pyogenes depends on proteins that are produced by
      this bacterium. The production of virulence proteins depends on environmental
      factors, and two-component regulatory systems are considered to be involved in
      sensing these factors. One of the environmental factors is acid stimuli. We
      established knockout strains in all speculated two-component regulatory sensor
      proteins of the M1 clinical strain of S. pyogenes and examined their relevance to
      acid stimuli. The parental strain and its derived knockout strains were cultured
      in a medium adjusted to pH 7.6 or 6.0, and their growth in broth was compared.
      The spy1622 sensor knockout strain showed significant growth reduction compared
      with the parental strain in broth at pH 6.0, suggesting that the Spy1622 two
      component sensor protein is involved in sensing acid stimuli. To further examine
      the role of the Spy1622 two-component sensor protein in virulence, blood
      bactericidal assays and mouse infection model experiments were performed. We
      found that the spy1622 knockout strain was less virulent than the parental
      strain, which suggests that the Spy1622 two-component sensor protein could play
      an important role in virulence.

PMID- 21873406
TI  - Genetic markers for Clostridium difficile lineages linked to hypervirulence.
AB  - Rapid identification of hypervirulent Clostridium difficile strains is essential
      for preventing their spread. Recent completion of several full-length C.
      difficile genomes provided an excellent opportunity to identify potentially
      unique genes that characterize hypervirulent strains. Based on sequence
      comparisons between C. difficile strains we describe two gene insertions into the
      genome of hypervirulent PCR ribotypes 078 and 027. Analysis of these regions, of
      1.7 and 4.2 kb, respectively, revealed that they contain several interesting
      ORFs. The 078 region is inserted intergenically and introduces an enzyme that is
      involved in the biosynthesis of several antibiotics. The 027 insert disrupts the
      thymidylate synthetase (thyX) gene and replaces it with an equivalent,
      catalytically more efficient, thyA gene. Both gene insertions were used to
      develop ribotype-specific PCRs, which were validated by screening a large strain
      collection consisting of 68 different PCR ribotypes supplemented with diverse 078
      and 027 strains derived from different geographical locations and individual
      outbreaks. The genetic markers were stably present in the hypervirulent PCR
      ribotypes 078 and 027, but were also found in several other PCR ribotypes.
      Comparative analysis of amplified fragment length polymorphisms, PCR ribotype
      banding patterns and toxin profiles showed that all PCR ribotypes sharing the
      same insert from phylogenetically coherent clusters. The identified loci are
      unique to these clusters, to which the hypervirulent ribotypes 078 and 027
      belong. This provides valuable information on strains belonging to two distinct
      lineages within C. difficile that are highly related to hypervirulent strains.

PMID- 21873407
TI  - Functional characterization of VC1929 of Vibrio cholerae El Tor: role in mannose
      sensitive haemagglutination, virulence and utilization of sialic acid.
AB  - The nonadhesive mutant CD11 of Vibrio cholerae El Tor, defective in expression of
      mannose-sensitive haemagglutinin, lacks a protein when compared with its parent
      strain. Determination of the amino acid sequence revealed the identity of the
      protein as the product of VC1929, which is annotated to encode a protein, DctP,
      involved in the transport of C4-dicarboxylates. We cloned the dctP gene in pUC19
      vector and expressed it in mutant CD11. Expression of DctP in the resulting
      complemented strain restored virulence, adhesive and colonizing capabilities,
      mannose-sensitive haemagglutination (MSHA) and ability to grow in medium
      containing sialic acid as a sole carbon source. The mutation in CD11 was caused
      by insertion of an adenine nucleotide in the reading frame of dctP. Recombinant
      purified DctP protein showed MSHA of human red blood cells, and protected rabbits
      against infection by V. cholerae. The protein was localized in membrane and cell
      wall fractions. The mutant, recombinant CD11 expressing DctP and parent strains
      were grown in M9 minimal medium in the presence of various carbohydrates
      (glucose, malate, fumarate, succinate or N-acetylneuraminic acid). The mutant was
      unable to grow in minimal medium containing N-acetylneuraminic acid (sialic acid)
      as the sole carbon source whereas the recombinant and parent strains utilized all
      the sugars tested. It is concluded that DctP is a mannose-sensitive
      haemagglutinin and a virulence factor and is involved in the utilization of
      sialic acid.

PMID- 21873408
TI  - Low oxygen induces the type III secretion system in Pseudomonas aeruginosa via
      modulation of the small RNAs rsmZ and rsmY.
AB  - A steep oxygen gradient within the mucus of the cystic fibrosis (CF) lung
      combined with the biofilm mode of bacterial growth forces respiratory pathogens
      to adapt to varying oxygen availability. This study presents the novel finding
      that the Pseudomonas aeruginosa response to limiting oxygen stress includes
      induction of its type III secretion system (T3SS), which subsequently contributes
      towards host cell cytotoxicity. In P. aeruginosa, the global anaerobic response
      regulator Anr perceives low oxygen and subsequently triggers gene expression of a
      range of target genes, including the response regulator narL. Here we demonstrate
      that microaerobic induction of the T3SS is dependent on Anr, and that this is
      mediated through direct NarL transcriptional repression of the sRNAs rsmY and
      rsmZ, allowing free RsmA protein to positively regulate the T3SS. This study
      reveals a novel interplay between the Anr-NarL and RsmAYZ regulatory circuits,
      and introduces RsmA as an important regulator during P. aeruginosa adaptation to
      a low-oxygen environment.

PMID- 21873409
TI  - Bacillus subtilis Fur represses one of two paralogous haem-degrading
      monooxygenases.
AB  - Identification of genes regulated by the ferric uptake regulator (Fur) protein
      has provided insights into the diverse mechanisms of adaptation to iron
      limitation. In the soil bacterium Bacillus subtilis, Fur senses iron sufficiency
      and represses genes that enable iron uptake, including biosynthetic and transport
      genes for the siderophore bacillibactin and uptake systems for siderophores
      produced by other organisms. We here demonstrate that Fur regulates hmoA
      (formerly yetG), which encodes a haem monooxygenase. HmoA is the first
      characterized member of a divergent group of putative monooxygenases that cluster
      separately from the well-characterized IsdG family. B. subtilis also encodes an
      IsdG family protein designated HmoB (formerly YhgC). Unlike hmoA, hmoB is
      constitutively expressed and not under Fur control. HmoA and HmoB both bind
      haemin in vitro with approximately 1 : 1 stoichiometry and degrade haemin in the
      presence of an electron donor. Mutational and spectroscopic analyses indicate
      that HmoA and HmoB have distinct active site architectures and interact
      differently with haem. We further show that B. subtilis can use haem as an iron
      source, but that this ability is independent of HmoA and HmoB.

PMID- 21873410
TI  - Self versus non-self: fungal cell wall degradation in Trichoderma.
AB  - Lysis of the prey's cell wall is one of the key steps during mycoparasitism.
      Genome analysis of two mycoparasitic Trichoderma species, T. atroviride and T.
      virens, revealed an expanded arsenal of genes encoding enzymes potentially
      involved in cell wall hydrolysis. Glycoside hydrolase family 18, which contains
      all fungal chitinases, is the largest family of carbohydrate-active enzymes in
      mycoparasitic Trichoderma species. However, in addition to their aggressive
      functions during mycoparasitism, the roles of chitinases and other cell wall
      degrading enzymes also include remodelling and recycling of the fungus's own cell
      wall. In this review we discuss current knowledge about fungal cell wall
      degrading enzymes in Trichoderma and how the fungus distinguishes between self-
      and non-self fungal cell wall degradation. In the past few years, the
      chitinolytic enzyme machinery of Trichoderma has been used as a model system to
      address this question. Gene expression profiles of most investigated chitinases
      indicate an overlap of functions of the respective enzymes and an involvement in
      both self- and non-self fungal cell wall degradation. Similar sets of enzymes
      appear to be involved in mycoparasitism, exogenous chitin decomposition and
      recycling of the fungus's own cell wall. Thus, we hypothesize that the regulation
      of self and non-self fungal cell wall degradation is not due to a speciation of
      individual chitinases. Rather, we hypothesize that it is regulated by substrate
      accessibility due to cell wall protection in healthy hyphae vs deprotection
      during mycoparasitic attack, hyphal ageing and autolysis.

PMID- 21873411
TI  - Nerve sheath tumor with degenerative atypia and multivacuolated lipoblasts.
AB  - Lipoblastic nerve sheath tumor is a recently described benign soft tissue tumor
      consisting of lipoblasts in a neural/schwannian background. The 6 reported cases
      have exclusively comprised signet ring lipoblasts and showed no cellular atypia.
      The authors describe the first lipoblastic nerve sheath tumor to harbor
      multivacuolated lipoblasts and degenerative atypia, underscoring its important
      differential diagnosis with well-differentiated liposarcoma. The purpose of this
      report is to expand the morphologic spectrum of this unusual neoplasm, and
      reemphasize the potential of benign nonadipocytic tumors to harbor
      multivacuolated lipoblasts and mimic liposarcoma.

PMID- 21873414
TI  - Venous surgical training in the era of endoluminal surgery.

PMID- 21873412
TI  - Functional selectivity at the MU-opioid receptor: implications for understanding
      opioid analgesia and tolerance.
AB  - Opioids are the most effective analgesic drugs for the management of moderate or
      severe pain, yet their clinical use is often limited because of the onset of
      adverse side effects. Drugs in this class produce most of their physiological
      effects through activation of the MU opioid receptor; however, an increasing
      number of studies demonstrate that different opioids, while presumably acting at
      this single receptor, can activate distinct downstream responses, a phenomenon
      termed functional selectivity. Functional selectivity of receptor-mediated events
      can manifest as a function of the drug used, the cellular or neuronal environment
      examined, or the signaling or behavioral measure recorded. This review summarizes
      both in vitro and in vivo work demonstrating functional selectivity at the MU
      opioid receptor in terms of G protein coupling, receptor phosphorylation,
      interactions with beta-arrestins, receptor desensitization, internalization and
      signaling, and details on how these differences may relate to the progression of
      analgesic tolerance after their extended use.

PMID- 21873416
TI  - Systematic reviews and meta-analyses.

PMID- 21873413
TI  - Regulation of G protein-coupled receptor function by Na+/H+ exchange regulatory
      factors.
AB  - Many G protein-coupled receptors (GPCR) exert patterns of cell-specific signaling
      and function. Mounting evidence now supports the view that cytoplasmic adapter
      proteins contribute critically to this behavior. Adapter proteins recognize
      highly conserved motifs such as those for Src homology 3 (SH3), phosphotyrosine
      binding (PTB), and postsynaptic density 95/discs-large/zona occludens (PDZ)
      docking sequences in candidate GPCRs. Here we review the behavior of the Na+/H+
      exchange regulatory factor (NHERF) family of PDZ adapter proteins on GPCR
      signalling, trafficking, and function. Structural determinants of NHERF proteins
      that allow them to recognize targeted GPCRs are considered. NHERF1 and NHERF2 are
      capable also of modifying the assembled complex of accessory proteins such as
      beta-arrestins, which have been implicated in regulating GPCR signaling. In
      addition, NHERF1 and NHERF2 modulate GPCR signaling by altering the G protein to
      which the receptor binds or affect other regulatory proteins that affect GTPase
      activity, protein kinase A, phospholipase C, or modify downstream signaling
      events. Small molecules targeting the site of NHERF1-GPCR interaction are being
      developed and may become important and selective drug candidates.

PMID- 21873417
TI  - ESC Guidelines on the diagnosis and treatment of peripheral artery diseases:
      Document covering atherosclerotic disease of extracranial carotid and vertebral,
      mesenteric, renal, upper and lower extremity arteries: the Task Force on the
      Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of
      Cardiology (ESC).

PMID- 21873418
TI  - ESC Guidelines on the management of cardiovascular diseases during pregnancy: the
      Task Force on the Management of Cardiovascular Diseases during Pregnancy of the
      European Society of Cardiology (ESC).

PMID- 21873419
TI  - ESC Guidelines for the management of acute coronary syndromes in patients
      presenting without persistent ST-segment elevation: The Task Force for the
      management of acute coronary syndromes (ACS) in patients presenting without
      persistent ST-segment elevation of the European Society of Cardiology (ESC).

PMID- 21873420
TI  - Identification and characterization of a new family of cell-penetrating peptides:
      cyclic cell-penetrating peptides.
AB  - Cell-penetrating peptides can translocate across the plasma membrane of living
      cells and thus are potentially useful agents in drug delivery applications.
      Disulfide-rich cyclic peptides also have promise in drug design because of their
      exceptional stability, but to date only one cyclic peptide has been reported to
      penetrate cells, the Momordica cochinchinensis trypsin inhibitor II (MCoTI-II).
      MCoTI-II belongs to the cyclotide family of plant-derived cyclic peptides that
      are characterized by a cyclic cystine knot motif. Previous studies in fixed cells
      showed that MCoTI-II could penetrate cells but kalata B1, a prototypic cyclotide
      from a separate subfamily of cyclotides, was bound to the plasma membrane and did
      not translocate into cells. Here, we show by live cell imaging that both MCoTI-II
      and kalata B1 can enter cells. Kalata B1 has the same cyclic cystine knot
      structural motif as MCoTI-II but differs significantly in sequence, and the
      mechanism by which these two peptides enter cells also differs. MCoTI-II appears
      to enter via macropinocytosis, presumably mediated by interaction of positively
      charged residues with phosphoinositides in the cell membrane, whereas kalata B1
      interacts directly with the membrane by targeting phosphatidylethanolamine
      phospholipids, probably leading to membrane bending and vesicle formation. We
      also show that another plant-derived cyclic peptide, SFTI-1, can penetrate cells.
      SFTI-1 includes just 14 amino acids and, with the exception of its cyclic
      backbone, is structurally very different from the cyclotides, which are twice the
      size. Intriguingly, SFTI-1 does not interact with any of the phospholipids
      tested, and its mechanism of penetration appears to be distinct from MCoTI-II and
      kalata B1. The ability of diverse disulfide-rich cyclic peptides to penetrate
      cells enhances their potential in drug design, and we propose a new
      classification for them, i.e. cyclic cell-penetrating peptides.

PMID- 21873421
TI  - Mucopolysaccharidosis type I, unique structure of accumulated heparan sulfate and
      increased N-sulfotransferase activity in mice lacking alpha-l-iduronidase.
AB  - Mucopolysaccharide (MPS) diseases are characterized by accumulation of
      glycosaminoglycans (GAGs) due to deficiencies in lysosomal enzymes responsible
      for GAG breakdown. Using a murine model of MPSI Hurler (MPSIH), we have
      quantified the heparan sulfate (HS) accumulation resulting from alpha-l
      iduronidase (Idua) deficiency. HS levels were significantly increased in liver
      and brain tissue from 12-week-old Idua(-/-) mice by 87- and 20-fold,
      respectively. In addition, HS chains were shown to contain significantly
      increased N-, 2-O-, and 6-O-sulfation. Disaccharide compositional analyses also
      uncovered an HS disaccharide uniquely enriched in MPSIH, representing the
      terminal iduronic acid residue capping the non-reducing end of the HS chain,
      where no further degradation can occur in the absence of Idua. Critically, we
      identified that excess HS, some of which is colocalized to the Golgi secretory
      pathway, acts as a positive regulator of HS-sulfation, increasing the N
      sulfotransferase activity of HS-modifying N-deacetylase/N-sulfotransferase
      enzymes. This mechanism may have severe implications during disease progression
      but, now identified, could help direct improved therapeutic strategies.

PMID- 21873422
TI  - Inhibition of c-Jun-N-terminal kinase increases cardiac peroxisome proliferator
      activated receptor alpha expression and fatty acid oxidation and prevents
      lipopolysaccharide-induced heart dysfunction.
AB  - Septic shock results from bacterial infection and is associated with multi-organ
      failure, high mortality, and cardiac dysfunction. Sepsis causes both myocardial
      inflammation and energy depletion. We hypothesized that reduced cardiac energy
      production is a primary cause of ventricular dysfunction in sepsis. The JNK
      pathway is activated in sepsis and has also been implicated in impaired fatty
      acid oxidation in several tissues. Therefore, we tested whether JNK activation
      inhibits cardiac fatty acid oxidation and whether blocking JNK would restore
      fatty acid oxidation during LPS treatment. LPS treatment of C57BL/6 mice and
      adenovirus-mediated activation of the JNK pathway in cardiomyocytes inhibited
      peroxisome proliferator-activated receptor alpha expression and fatty acid
      oxidation. Surprisingly, none of the adaptive responses that have been described
      in other types of heart failure, such as increased glucose utilization, reduced
      alphaMHC:betaMHC ratio or induction of certain microRNAs, occurred in LPS-treated
      mice. Treatment of C57BL/6 mice with a general JNK inhibitor (SP600125) increased
      fatty acid oxidation in mice and a cardiomyocyte-derived cell line. JNK
      inhibition also prevented LPS-mediated reduction in fatty acid oxidation and
      cardiac dysfunction. Inflammation was not alleviated in LPS-treated mice that
      received the JNK inhibitor. We conclude that activation of JNK signaling reduces
      fatty acid oxidation and prevents the peroxisome proliferator-activated receptor
      alpha down-regulation that occurs with LPS.

PMID- 21873423
TI  - Active ERK1/2 protein interacts with the phosphorylated nuclear constitutive
      active/androstane receptor (CAR; NR1I3), repressing dephosphorylation and
      sequestering CAR in the cytoplasm.
AB  - The nuclear constitutive active/androstane receptor (CAR) is inactivated and
      sequestered in the cytoplasm when Thr-38 is phosphorylated. Here, we have
      demonstrated that activated ERK1/2 interacts with phosphorylated CAR to repress
      dephosphorylation of Thr-38. The phosphorylation-dependent interaction between
      CAR and ERK1/2 was examined by co-immunoprecipitation experiments of ectopically
      expressed FLAG-tagged CAR T38A and CAR T38D mutants with endogenous phospho
      ERK1/2 in Huh-7 cells. Phospho-ERK1/2 coprecipitated only the phosphorylation
      mimicking CAR T38D mutant; this coprecipitation was mediated by the interaction
      with the xenochemical response signal peptide near the C terminus of CAR. This
      interaction increased after EGF treatment and decreased after treatment with the
      MEK inhibitor U0126 as well as after knockdown of MEK1/2 by shRNA in Huh-7 cells.
      The phosphorylation levels of Thr-38 of CAR decreased in U0126-treated Huh-7
      cells. Thus, activated ERK1/2 interacts with CAR and represses dephosphorylation
      of Thr-38, providing a cell signal-regulated mechanism for CAR activation.

PMID- 21873424
TI  - BRI2 protein regulates beta-amyloid degradation by increasing levels of secreted
      insulin-degrading enzyme (IDE).
AB  - The amyloid precursor protein (APP) is one of the major proteins involved in
      Alzheimer disease (AD). Proteolytic cleavage of APP gives rise to amyloid-beta
      (Abeta) peptides that aggregate and deposit extensively in the brain of AD
      patients. Although the increase in levels of aberrantly folded Abeta peptide is
      considered to be important to disease pathogenesis, the regulation of APP
      processing and Abeta metabolism is not fully understood. Recently, the British
      precursor protein (BRI2, ITM2B) has been implicated in influencing APP processing
      in cells and Abeta deposition in vivo. Here, we show that the wild type BRI2
      protein reduces plaque load in an AD mouse model, similar to its disease
      associated mutant form, ADan precursor protein (ADanPP), and analyze in more
      detail the mechanism of how BRI2 and ADanPP influence APP processing and Abeta
      metabolism. We find that overexpression of either BRI2 or ADanPP reduces
      extracellular Abeta by increasing levels of secreted insulin-degrading enzyme
      (IDE), a major Abeta-degrading protease. This effect is also observed with BRI2
      lacking its C-terminal 23-amino acid peptide sequence. Our results suggest that
      BRI2 might act as a receptor protein that regulates IDE levels that in turn
      influences APP metabolism in a previously unrecognized way. Targeting the
      regulation of IDE may be a promising therapeutic approach to sporadic AD.

PMID- 21873425
TI  - Taurine-containing uridine modifications in tRNA anticodons are required to
      decipher non-universal genetic codes in ascidian mitochondria.
AB  - Variations in the genetic code are found frequently in mitochondrial decoding
      systems. Four non-universal genetic codes are employed in ascidian mitochondria:
      AUA for Met, UGA for Trp, and AGA/AGG(AGR) for Gly. To clarify the decoding
      mechanism for the non-universal genetic codes, we isolated and analyzed
      mitochondrial tRNAs for Trp, Met, and Gly from an ascidian, Halocynthia roretzi.
      Mass spectrometric analysis identified 5-taurinomethyluridine (taum(5)U) at the
      anticodon wobble positions of tRNA(Met)(AUR), tRNA(Trp)(UGR), and tRNA(Gly)(AGR),
      suggesting that taum(5)U plays a critical role in the accurate deciphering of all
      four non-universal codes by preventing the misreading of pyrimidine-ending near
      cognate codons (NNY) in their respective family boxes. Acquisition of the wobble
      modification appears to be a prerequisite for the genetic code alteration.

PMID- 21873426
TI  - Termination of protein synthesis in mammalian mitochondria.
AB  - All mechanisms of protein synthesis can be considered in four stages: initiation,
      elongation, termination, and ribosome recycling. Remarkable progress has been
      made in understanding how these processes are mediated in the cytosol of many
      species; however, details of organellar protein synthesis remain sketchy. This is
      an important omission, as defects in human mitochondrial translation are known to
      cause disease and may contribute to the aging process itself. In this minireview,
      we focus on the recent advances that have been made in understanding how one of
      these processes, translation termination, occurs in the human mitochondrion.

PMID- 21873427
TI  - Induction of apoptotic genes by a p73-phosphatase and tensin homolog (p73-PTEN)
      protein complex in response to genotoxic stress.
AB  - The p53 family member, p73, has been characterized as a tumor suppressor and
      functions in a similar manner as p53 to induce cellular death. The phosphatase
      and tensin homolog (PTEN) can function as a dual specificity lipid/protein
      phosphatase. However, recent data have described multiple roles for nuclear PTEN
      independent of its lipid phosphatase activity. PTEN can directly or indirectly
      activate p53 to promote apoptosis. We examined whether PTEN would interact and
      regulate p73 independent of p53. Co-localization in the nucleus and complex
      formation of p73/PTEN were observed after DNA damage. Furthermore, we also
      demonstrate that p73alpha/PTEN proteins directly bind one another. Both
      overexpressed and endogenous p73-PTEN interactions were determined to be the
      strongest in the nuclear fraction after DNA damage, which suggested formation of
      a transcriptional complex. We employed chromatin immunoprecipitation (ChIP) and
      found that p73 and PTEN were associated with the PUMA promoter after genotoxic
      stress in TP53-null cells. We found that another p73 target, BAX, had an
      increased expression in the presence of p73 and PTEN. In addition, in virus
      transduced cell lines stably expressing p73, PTEN, or both p73/PTEN, we found
      that the p73/PTEN cells were more sensitive to genotoxic stress and cellular
      death as measured by increased poly(ADP-ribose) polymerase cleavage and PUMA/Bax
      induction. Conversely, knockdown of PTEN dramatically reduced Bax and PUMA
      levels. Thus, a p73-PTEN protein complex is engaged to induce apoptosis
      independent of p53 in response to DNA damage.

PMID- 21873428
TI  - Reporter mutation studies show that nicotinic acetylcholine receptor (nAChR)
      alpha5 Subunits and/or variants modulate function of alpha6*-nAChR.
AB  - To further the understanding of functional alpha6alpha5*-nicotinic acetylcholine
      receptors (nAChR; the asterisk (*) indicates known or possible presence of other
      subunits), we have heterologously expressed in oocytes different, mouse or human,
      nAChR subunit combinations. Coexpression with wild-type alpha5 subunits or
      chimeric alpha5/beta3 subunits (in which the human alpha5 subunit N-terminal,
      extracellular domain is linked to the remaining domains of the human beta3
      subunit) almost completely abolishes the very small amount of function seen for
      alpha6beta4*-nAChR and does not induce function of alpha6beta2*-nAChR.
      Coexpression with human alpha5(V9)'(S) subunits bearing a valine 290 to serine
      mutation in the 9' position of the second transmembrane domain does not rescue
      the function of alpha6beta4*-nAChR or induce function of alpha6beta2*-nAChR.
      However, coexpression with mutant chimeric alpha5/beta3(V9)'(S) subunits has a
      gain-of-function effect (higher functional expression and agonist sensitivity and
      spontaneous opening inhibited by mecamylamine) on alpha6beta4*-nAChR. Moreover,
      N143D + M145V mutations in the alpha6 subunit N-terminal domain enable
      alpha5/beta3(V9)'(S) subunits to have a gain-of-function effect on alpha6beta2*
      nAChR. nAChR containing chimeric alpha6/alpha3 subunits plus either beta2 or
      beta4 subunits have some function that is modulated in the presence of alpha5 or
      alpha5/beta3 subunits. Coexpression with alpha5/beta3(V9)'(S) subunits has a gain
      of-function effect more pronounced than that in the presence of alpha5(V9)'(S)
      subunits. Gain-of-function effects are dependent, sometimes subtly, on the nature
      and apparently the extracellular, cytoplasmic, and/or transmembrane domain
      topology of partner subunits. These studies yield insight into assembly of
      functional alpha6alpha5*-nAChR and provide tools for development of alpha6*-nAChR
      selective ligands that could be important in the treatment of nicotine
      dependence, and perhaps other neurological diseases.

PMID- 21873429
TI  - Ca2+ influx through reverse mode Na+/Ca2+ exchange is critical for vascular
      endothelial growth factor-mediated extracellular signal-regulated kinase (ERK)
      1/2 activation and angiogenic functions of human endothelial cells.
AB  - VEGF is a key angiogenic cytokine and a major target in anti-angiogenic
      therapeutic strategies. In endothelial cells (ECs), VEGF binds VEGF receptors and
      activates ERK1/2 through the phospholipase gamma (PLCgamma)-PKCalpha-B-Raf
      pathway. Our previous work suggested that influx of extracellular Ca(2+) is
      required for VEGF-induced ERK1/2 activation, and we hypothesized that this could
      occur through reverse mode (Ca(2+) in and Na(+) out) Na(+)-Ca(2+) exchange (NCX).
      However, the role of NCX activity in VEGF signaling and angiogenic functions of
      ECs had not previously been described. Here, using human umbilical vein ECs
      (HUVECs), we report that extracellular Ca(2+) is required for VEGF-induced ERK1/2
      activation and that release of Ca(2+) from intracellular stores alone, in the
      absence of extracellular Ca(2+), is not sufficient to activate ERK1/2.
      Furthermore, inhibitors of reverse mode NCX suppressed the VEGF-induced
      activation of ERK1/2 in a time- and dose-dependent manner and attenuated VEGF
      induced Ca(2+) transients. Knockdown of NCX1 (the main NCX isoform in HUVECs) by
      siRNA confirmed the pharmacological data. A panel of NCX inhibitors also
      significantly reduced VEGF-induced B-Raf activity and inhibited PKCalpha
      translocation to the plasma membrane and total PKC activity in situ. Finally, NCX
      inhibitors reduced VEGF-induced HUVEC proliferation, migration, and tubular
      differentiation in surrogate angiogenesis functional assays in vitro. We propose
      that Ca(2+) influx through reverse mode NCX is required for the activation and
      the targeting of PKCalpha to the plasma membrane, an essential step for VEGF
      induced ERK1/2 phosphorylation and downstream EC functions in angiogenesis.

PMID- 21873430
TI  - The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to
      regulate expression of proapoptotic and cell cycle control genes by
      phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling.
AB  - Phosphatidylinositol (PI) 3-kinase/Akt signaling plays a critical role in cell
      proliferation and survival, partly by regulation of FoxO transcription factors.
      Previous work using global expression profiling indicated that inhibition of PI 3
      kinase in proliferating cells led to induction of genes that promote cell cycle
      arrest and apoptosis. The upstream regulatory regions of these genes had binding
      sites not only for FoxO, but also for Myc/Max transcription factors. In the
      present study, we have addressed the role of Myc family members and related E-box
      binding proteins in the regulation of these genes. Chromatin immunoprecipitations
      and RNA interference indicated that transcription was repressed by Max-Mnt-Sin3a
      histone deacetylase complexes in proliferating cells. Inhibition of PI 3-kinase
      led to a loss of Max/Mnt binding and transcriptional induction by MITF and USF1,
      as well as FoxO. Both MITF and USF1 were activated by glycogen synthase kinase
      (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously
      described activating site threonine 153 as well as serine 186. siRNA against MITF
      as well as against FoxO3a protected cells from apoptosis following PI 3-kinase
      inhibition. These results define a novel E-box-regulated network that functions
      coordinately with FoxO to regulate transcription of apoptotic and cell cycle
      regulatory genes downstream of PI 3-kinase/Akt/GSK3 signaling.

PMID- 21873431
TI  - Role of dynamics in the autoinhibition and activation of the exchange protein
      directly activated by cyclic AMP (EPAC).
AB  - The exchange protein directly activated by cAMP (EPAC) is a key receptor of cAMP
      in eukaryotes and controls critical signaling pathways. Currently, no residue
      resolution information is available on the full-length EPAC dynamics, which are
      known to be pivotal determinants of allostery. In addition, no information is
      presently available on the intermediates for the classical induced fit and
      conformational selection activation pathways. Here these questions are addressed
      through molecular dynamics simulations on five key states along the thermodynamic
      cycle for the cAMP-dependent activation of a fully functional construct of EPAC2,
      which includes the cAMP-binding domain and the integral catalytic region. The
      simulations are not only validated by the agreement with the experimental trends
      in cAMP-binding domain dynamics determined by NMR, but they also reveal
      unanticipated dynamic attributes, rationalizing previously unexplained aspects of
      EPAC activation and autoinhibition. Specifically, the simulations show that cAMP
      binding causes an extensive perturbation of dynamics in the distal catalytic
      region, assisting the recognition of the Rap1b substrate. In addition, analysis
      of the activation intermediates points to a possible hybrid mechanism of EPAC
      allostery incorporating elements of both the induced fit and conformational
      selection models. In this mechanism an entropy compensation strategy results in a
      low free-energy pathway of activation. Furthermore, the simulations indicate that
      the autoinhibitory interactions of EPAC are more dynamic than previously
      anticipated, leading to a revised model of autoinhibition in which dynamics fine
      tune the stability of the autoinhibited state, optimally sensitizing it to cAMP
      while avoiding constitutive activation.

PMID- 21873432
TI  - Neu1 sialidase and matrix metalloproteinase-9 cross-talk is essential for Toll
      like receptor activation and cellular signaling.
AB  - The signaling pathways of mammalian Toll-like receptors (TLRs) are well
      characterized, but the precise mechanism(s) by which TLRs are activated upon
      ligand binding remains poorly defined. Recently, we reported a novel membrane
      sialidase-controlling mechanism that depends on ligand binding to its TLR to
      induce mammalian neuraminidase-1 (Neu1) activity, to influence receptor
      desialylation, and subsequently to induce TLR receptor activation and the
      production of nitric oxide and proinflammatory cytokines in dendritic and
      macrophage cells. The alpha-2,3-sialyl residue of TLR was identified as the
      specific target for hydrolysis by Neu1. Here, we report a membrane signaling
      paradigm initiated by endotoxin lipopolysaccharide (LPS) binding to TLR4 to
      potentiate G protein-coupled receptor (GPCR) signaling via membrane Galpha(i)
      subunit proteins and matrix metalloproteinase-9 (MMP9) activation to induce Neu1.
      Central to this process is that a Neu1-MMP9 complex is bound to TLR4 on the cell
      surface of naive macrophage cells. Specific inhibition of MMP9 and GPCR Galpha(i)
      signaling proteins blocks LPS-induced Neu1 activity and NFkappaB activation.
      Silencing MMP9 mRNA using lentivirus MMP9 shRNA transduction or siRNA
      transfection of macrophage cells and MMP9 knock-out primary macrophage cells
      significantly reduced Neu1 activity and NFkappaB activation associated with LPS
      treated cells. These findings uncover a molecular organizational signaling
      platform of a novel Neu1 and MMP9 cross-talk in alliance with TLR4 on the cell
      surface that is essential for ligand activation of TLRs and subsequent cellular
      signaling.

PMID- 21873433
TI  - Suppression of 5'-nucleotidase enzymes promotes AMP-activated protein kinase
      (AMPK) phosphorylation and metabolism in human and mouse skeletal muscle.
AB  - The 5'-nucleotidase (NT5) family of enzyme dephosphorylates non-cyclic nucleoside
      monophosphates to produce nucleosides and inorganic phosphates. We hypothesized
      that gene silencing of NT5 enzymes to increase the intracellular availability of
      AMP would increase AMP-activated protein kinase (AMPK) activity and metabolism.
      We determined the role of cytosolic NT5 in metabolic responses linked to the
      development of insulin resistance in obesity and type 2 diabetes. Using siRNA to
      silence NT5C2 expression in cultured human myotubes, we observed a 2-fold
      increase in the AMP/ATP ratio, a 2.4-fold increase in AMPK phosphorylation
      (Thr(172)), and a 2.8-fold increase in acetyl-CoA carboxylase phosphorylation
      (Ser(79)) (p < 0.05). siRNA silencing of NT5C2 expression increased palmitate
      oxidation by 2-fold in the absence and by 8-fold in the presence of 5
      aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside. This was paralleled by an
      increase in glucose transport and a decrease in glucose oxidation, incorporation
      into glycogen, and lactate release from NT5C2-depleted myotubes. Gene silencing
      of NT5C1A by shRNA injection and electroporation in mouse tibialis anterior
      muscle reduced protein content (60%; p < 0.05) and increased phosphorylation of
      AMPK (60%; p < 0.05) and acetyl-CoA carboxylase (50%; p < 0.05) and glucose
      uptake (20%; p < 0.05). Endogenous expression of NT5C enzymes inhibited basal
      lipid oxidation and glucose transport in skeletal muscle. Reduction of 5'
      nucleotidase expression or activity may promote metabolic flexibility in type 2
      diabetes.

PMID- 21873434
TI  - Median neuropathy caused by giant lipoma in the pronator quadratus: a case
      report.

PMID- 21873435
TI  - Expansile aneurysmal bone cyst in the tubular bones of the hand treated with en
      bloc excision and autograft reconstruction: a report of 12 cases.
AB  - Primary aneurysmal bone cysts (ABCs) in the small tubular bones of the hands are
      rare and optimal treatment is not yet established. Between August 1997 and June
      2009, 12 patients with biopsy-proven expansile primary ABCs of the small tubular
      bones of the hand were treated with en bloc tumor excision and strut autograft
      reconstruction. The adjacent joint was preserved if feasible, otherwise it was
      fused. Patients were followed for at least 2 years (mean = 7 years). All grafts
      were incorporated except for partial resorption in one. There was only one tumor
      recurrence about 1 year after the operation. Other complications included
      premature physeal arrest in one case and limitation of adjacent joint motion in
      three. A relatively low rate of recurrence and other complications indicates that
      this technique would serve as a good strategy for patients with expansile ABCs in
      the hand in terms of safety, simplicity and reduced number of re-operations.

PMID- 21873436
TI  - Do the dimensions of the distal phalanges allow suture anchor fixation of the
      flexor digitorum profundus? A cadaver study.
AB  - This study was done to identify whether the dimensions of the distal phalanges
      allow suture anchor fixation of the flexor digitorum profundus tendon. Forty
      pairs of hands were dissected to measure the anteroposterior and lateral
      dimensions of distal phalanges of all digits. The mean anteroposterior depth of
      the distal phalanx at the insertion of the tendon was found to be 4.7 mm for the
      little finger, 5.4 mm for the ring finger, 5.9 mm for the middle finger, 5.4 mm
      for the index finger and 6.9 mm for the thumb respectively. The commonly
      available anchors and drill bits for fingers were found to be suboptimal for
      anchoring the flexor digitorum profundus tendon to the distal phalanx of the
      little finger. The drill bits used for these anchors were found to be too long
      for the little fingers and some ring and index fingers.

PMID- 21873437
TI  - A modified towel test for assessment of elbow flexion in children less than 9
      months old with brachial plexus birth palsy.

PMID- 21873438
TI  - Closed rupture of brachioradialis during exercise.

PMID- 21873439
TI  - Re: Incoll IW et al. Comparison of the effectiveness of painting onto the hand
      and immersing the hand in a bag, in pre-operative skin preparation of the hand. J
      Hand Surg Eur. 2009, 34: 371-3.

PMID- 21873441
TI  - Cardiac MRI as end point in clinical trials.

PMID- 21873440
TI  - Safety of serial MRI in patients with implantable cardioverter defibrillators.
AB  - OBJECTIVE: While patients with cardiac implantable electronic devices could
      benefit from magnetic resonance (MR) imaging, the presence of such devices has
      been designated as an absolute contraindication to MR. Although scanning
      algorithms are proposed for cardiac implantable electronic devices, their safety
      remains uncertain. To address this issue, the safety of serial cardiac MR scans
      was evaluated in patients with implantable cardioverter defibrillators (ICDs).
      METHODS: Three serial cardiac MR scans were prospectively performed at 1.5 T on
      10 patients (9 men) of median age 56 years (range 51-68) with ICDs. ICD
      interrogation was performed before and after the MR scan and at a follow-up of
      median 370 days (range 274-723). Image quality was also assessed. RESULTS: In all
      patients MR scanning occurred without complications. There were no differences
      between pre- and post-MR pacing capture threshold, pacing lead or high voltage
      lead impedance, or battery voltage values. During follow-up there were no
      occurrences of ICD dysfunction. Although most patients had image artifacts, the
      studies were generally diagnostic regarding left ventricular function and wall
      motion. Delayed enhancement imaging was of good quality for inferior wall and
      inferolateral infarcts, but ICD artifacts often affected the imaging of anterior
      wall infarcts. CONCLUSION: Serial MR scans at 1.5 T in patients with ICDs, when
      carefully performed in a monitored setting, have no adverse effects on either
      patient or device. When required, single or multiple MR scans at 1.5 T may
      therefore be considered for clinical diagnostic purposes in these patients.

PMID- 21873443
TI  - Bradykinin does not mediate remote ischaemic preconditioning or ischaemia
      reperfusion injury in vivo in man.
AB  - OBJECTIVE: To examine whether endogenous bradykinin mediates the endothelium
      dependent vasomotor dysfunction induced by ischaemia-reperfusion injury, or the
      protection afforded by remote ischaemic preconditioning in vivo in man. DESIGN:
      Randomised double-blind, cross-over study. SETTINGS: Royal Infirmary of
      Edinburgh, Wellcome Trust Clinical Research Facility. PATIENTS: Twenty healthy
      male volunteers. INTERVENTIONS: Subjects were randomised to intravenous infusion
      of the bradykinin B(2) receptor antagonist, HOE-140 (100 MUg/kg), or saline
      placebo in a double-blind, crossover trial. Ischaemia-reperfusion injury was
      induced in the non-dominant arm by inflating a cuff to 200 mm Hg for 20 min in
      all subjects. Ischaemia-reperfusion injury was preceded by three cycles of remote
      ischaemic preconditioning in the dominant arm in 10 subjects. MAIN OUTCOME
      MEASURES: Bilateral forearm blood flow was assessed using venous occlusion
      plethysmography during intra-arterial infusion of acetylcholine (5-20 MUg/min).
      RESULTS: Acetylcholine caused vasodilatation in all studies (p<0.05) that was
      attenuated by ischaemia-reperfusion injury, both in the presence (p=0.0002) and
      absence (p=0.04) of HOE-140. Remote ischaemic preconditioning abolished the
      impairment of endothelium-dependent vasomotor function induced by ischaemia
      reperfusion injury. HOE-140 had no effect on the protection afforded by remote
      ischaemic preconditioning. CONCLUSIONS: These findings do not support a major
      role for endogenous bradykinin, acting via the B(2) kinin receptor, in the
      mechanism of ischaemia-reperfusion injury or the protective effects of remote
      ischaemic preconditioning in man. CLINICAL TRIAL REGISTRATION INFORMATION:
      NCT00965120 and NCT00965393.

PMID- 21873444
TI  - Mechanisms of lung endothelial barrier disruption induced by cigarette smoke:
      role of oxidative stress and ceramides.
AB  - The epithelial and endothelial cells lining the alveolus form a barrier essential
      for the preservation of the lung respiratory function, which is, however,
      vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas
      profound breaches in this barrier function cause pulmonary edema, more subtle
      changes may contribute to inflammation. The mechanisms by which cigarette smoke
      (CS) exposure induce lung inflammation are not fully understood, but an early
      alteration in the epithelial barrier function has been documented. We sought to
      investigate the occurrence and mechanisms by which soluble components of
      mainstream CS disrupt the lung endothelial cell barrier function. Using cultured
      primary rat microvascular cell monolayers, we report that CS induces endothelial
      cell barrier disruption in a dose- and time-dependent manner of similar magnitude
      to that of the epithelial cell barrier. CS exposure triggered a mechanism of
      neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK
      activation that were oxidative stress dependent and that, along with Rho kinase
      activation, mediated the endothelial barrier dysfunction. The morphological
      changes in endothelial cell monolayers induced by CS included actin cytoskeletal
      rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap
      formation, which were abolished by the glutathione modulator N-acetylcysteine and
      ameliorated by neutral sphingomyelinase inhibition. The direct application of
      ceramide recapitulated the effects of CS, by disrupting both endothelial and
      epithelial cells barrier, by a mechanism that was redox and apoptosis independent
      and required Rho kinase activation. Furthermore, ceramide induced dose-dependent
      alterations of alveolar microcirculatory barrier in vivo, measured by two-photon
      excitation microscopy in the intact rat. In conclusion, soluble components of CS
      have direct endothelial barrier-disruptive effects that could be ameliorated by
      glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK,
      JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung
      and systemic vascular dysfunction associated with smoking-related chronic
      obstructive lung diseases.

PMID- 21873445
TI  - What do we know about mechanical strain in lung alveoli?
AB  - The pulmonary alveolus, terminal gas-exchange unit of the lung, is composed of
      alveolar epithelial and endothelial cells separated by a thin basement membrane
      and interstitial space. These cells participate in the maintenance of a delicate
      system regulated not only by biological factors but also by the mechanical
      environment of the lung, which undergoes dynamic deformation during breathing.
      Clinical and animal studies as well as cell culture studies point toward a strong
      influence of mechanical forces on lung cells and tissues including effects on
      growth and repair, surfactant release, injury, and inflammation. However, despite
      substantial advances in our understanding of lung mechanics over the last half
      century, there are still many unanswered questions regarding the micromechanics
      of the alveolus and how it deforms during lung inflation. Therefore, the aims of
      this review are to draw a multidisciplinary account of the mechanics of the
      alveolus on the basis of its structure, biology, and chemistry and to compare
      estimates of alveolar deformation from previous studies.

PMID- 21873447
TI  - TAK1 plays a major role in growth factor-induced phenotypic modulation of airway
      smooth muscle.
AB  - Increased airway smooth muscle (ASM) mass is a major feature of airway remodeling
      in asthma and chronic obstructive pulmonary disease. Growth factors induce a
      proliferative ASM phenotype, characterized by an increased proliferative state
      and a decreased contractile protein expression, reducing contractility of the
      muscle. Transforming growth factor-beta-activated kinase 1 (TAK1), a mitogen
      activated protein kinase kinase kinase, is a key enzyme in proinflammatory
      signaling in various cell types; however, its function in ASM is unknown. The aim
      of this study was to investigate the role of TAK1 in growth factor-induced
      phenotypic modulation of ASM. Using bovine tracheal smooth muscle (BTSM) strips
      and cells, as well as human tracheal smooth muscle cells, we investigated the
      role of TAK1 in growth factor-induced proliferation and hypocontractility.
      Platelet-derived growth factor- (PDGF; 10 ng/ml) and fetal bovine serum (5%)
      induced increases in DNA synthesis and cell number in bovine and human cells were
      significantly inhibited by pretreatment with the specific TAK1 inhibitor LL-Z
      1640-2 (5Z-7-oxozeaenol; 100 nM). PDGF-induced DNA synthesis and extracellular
      signal-regulated kinase-1/2 phosphorylation in BTSM cells were strongly inhibited
      by both LL-Z-1640-2 pretreatment and transfection of dominant-negative TAK1. In
      addition, LL-Z-1640-2 inhibited PDGF-induced reduction of BTSM contractility and
      smooth muscle alpha-actin expression. The data indicate that TAK1 plays a major
      role in growth factor-induced phenotypic modulation of ASM.

PMID- 21873446
TI  - Intrauterine growth restriction decreases pulmonary alveolar and vessel growth
      and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep.
AB  - Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary
      dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR,
      but whether IUGR adversely impacts fetal pulmonary vascular development and
      pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized
      that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in
      vitro PAEC function. Studies were performed in an established model of severe
      placental insufficiency and IUGR induced by exposing pregnant sheep to elevated
      temperatures. Alveolarization, quantified by radial alveolar counts, was
      decreased 20% (P < 0.005) in IUGR fetuses. Pulmonary vessel density was decreased
      44% (P < 0.01) in IUGR fetuses. In vitro, insulin increased control PAEC
      migration, tube formation, and nitric oxide (NO) production. This response was
      absent in IUGR PAECs. VEGFA stimulated tube formation, and NO production also was
      absent. In control PAECs, insulin increased cell growth by 68% (P < 0.0001). Cell
      growth was reduced in IUGR PAECs by 29% at baseline (P < 0.01), and the response
      to insulin was attenuated (P < 0.005). Despite increased basal and insulin
      stimulated Akt phosphorylation in IUGR PAECs, endothelial NO synthase (eNOS)
      protein expression as well as basal and insulin-stimulated eNOS phosphorylation
      were decreased in IUGR PAECs. Both VEGFA and VEGFR2 also were decreased in IUGR
      PAECs. We conclude that fetuses with IUGR are characterized by decreased alveolar
      and vascular growth and PAEC dysfunction in vitro. This may contribute to the
      increased risk for adverse respiratory outcomes and BPD in infants with IUGR.

PMID- 21873448
TI  - Phosphatidylinositol 4,5-bisphosphate stimulates alveolar epithelial fluid
      clearance in male and female adult rats.
AB  - Cell membrane phospholipids, like phosphatidylinositol 4,5-bisphosphate
      [PI(4,5)P(2)], can regulate epithelial Na channel (ENaC) activity. Gender
      differences in lung ENaC expression have also been demonstrated. However, the
      effects in vivo on alveolar fluid clearance are uncertain. Thus PI(4,5)P(2)
      effects on alveolar fluid clearance were studied in male and female rats. An
      isosmolar 5% albumin solution was intrapulmonary instilled; alveolar fluid
      clearance was studied for 1 h. Female rats had a 37 +/- 19% higher baseline
      alveolar fluid clearance than male rats. Bilateral ovariectomy attenuated this
      gender difference. Compared with controls, PI(4,5)P(2) instillation (300 MUM)
      increased alveolar fluid clearance by ~93% in both genders. Amiloride or the
      specific alphaENaC small-interfering RNA inhibited baseline and PI(4,5)P(2)
      stimulated alveolar fluid clearance in both genders, indicating a dependence on
      amiloride-sensitive pathways. The fraction of amiloride inhibition was greater in
      PI(4,5)P(2)-instilled rats (male: 64 +/- 10%; female: 70 +/- 11%) than in
      controls (male: 30 +/- 6%; female: 44 +/- 8%). PI(4,5)P(2) instillation lacked
      additional alveolar fluid clearance stimulation above that of terbutaline, nor
      did propranolol inhibit alveolar fluid clearance after PI(4,5)P(2) instillation,
      indicating that PI(4,5)P(2) stimulation was not secondary to endogenous beta
      adrenoceptor activation. PI(4,5)P(2) amine instillation resulted in an
      intermediate alveolar fluid clearance stimulation, suggesting that, to reach
      maximal alveolar fluid clearance stimulation, PI(4,5)P(2) must reside in cell
      membranes. In summary, PI(4,5)P(2) instillation upregulated in vivo alveolar
      fluid clearance similar to short-term beta-adrenoceptor upregulation of alveolar
      fluid clearance. PI(4,5)P(2) stimulation was mediated partly by increased
      amiloride-sensitive Na transport. There exist important gender-related effects
      suggesting a female advantage that may have clinical implications for resolution
      of acute lung injury.

PMID- 21873449
TI  - Regulation of monocyte subset proinflammatory responses within the lung
      microvasculature by the p38 MAPK/MK2 pathway.
AB  - Margination and activation of monocytes within the pulmonary microcirculation
      contribute substantially to the development of acute lung injury in mice. The
      enhanced LPS-induced TNF expression exhibited by Gr-1(high) compared with Gr
      1(low) monocytes within the lung microvasculature suggests differential roles for
      these subsets. We investigated the mechanisms responsible for such heterogeneity
      of lung-marginated monocyte proinflammatory response using a combined in vitro
      and in vivo approach. The monocyte subset inflammatory response was studied in
      vitro in mouse peripheral blood mononuclear cell-lung endothelial cell coculture
      and in vivo in a two-hit model of intravenous LPS-induced monocyte margination
      and lung inflammation in mice, by flow cytometry-based quantification of
      proinflammatory genes and intracellular phospho-kinases. With LPS stimulation in
      vitro, TNF expression was consistently higher in Gr-1(high) than Gr-1(low)
      monocytes, markedly enhanced by coculture with endothelial cells, and abrogated
      by p38 MAPK inhibitors. Expression of IL-6, inducible nitric oxide synthase
      (iNOS), and cyclooxygenase-2 (COX-2) was only detectable under coculture
      conditions, was substantially higher in Gr-1(high) monocytes, and was attenuated
      by p38 inhibition. Consistent with these differential responses, phosphorylation
      of p38 and its substrate MAPK-activated protein kinase 2 (MK2) was significantly
      higher in the Gr-1(high) subset. In vivo, p38 inhibitor treatment significantly
      attenuated LPS-induced TNF expression in "lung-marginated" Gr-1(high) monocytes.
      LPS-induced p38/MK2 phosphorylation was higher in lung-marginated Gr-1(high) than
      Gr-1(low) monocytes and neutrophils, mirroring TNF expression. These results
      indicate that the p38/MK2 pathway is a critical determinant of elevated Gr
      1(high) subset responsiveness within the lung microvasculature, producing a
      coordinated proinflammatory response that places Gr-1(high) monocytes as key
      orchestrators of pulmonary microvascular inflammation and injury.

PMID- 21873450
TI  - Stereological analysis of bacterial load and lung lesions in nonhuman primates
      (rhesus macaques) experimentally infected with Mycobacterium tuberculosis.
AB  - Infection with Mycobacterium tuberculosis primarily produces a multifocal
      distribution of pulmonary granulomas in which the pathogen resides. Accordingly,
      quantitative assessment of the bacterial load and pathology is a substantial
      challenge in tuberculosis. Such assessments are critical for studies of the
      pathogenesis and for the development of vaccines and drugs in animal models of
      experimental M. tuberculosis infection. Stereology enables unbiased quantitation
      of three-dimensional objects from two-dimensional sections and thus is suited to
      quantify histological lesions. We have developed a protocol for stereological
      analysis of the lung in rhesus macaques inoculated with a pathogenic clinical
      strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of
      infection and tuberculosis similar to that of naturally infected humans.
      Conditions were optimized for collecting lung samples in a nonbiased, random
      manner. Bacterial load in these samples was assessed by a standard plating assay,
      and granulomas were graded and enumerated microscopically. Stereological analysis
      provided quantitative data that supported a significant correlation between
      bacterial load and lung granulomas. Thus this stereological approach enables a
      quantitative, statistically valid analysis of the impact of M. tuberculosis
      infection in the lung and will serve as an essential tool for objectively
      comparing the efficacy of drugs and vaccines.

PMID- 21873451
TI  - Airway remodeling in murine asthma correlates with a defect in PGE2 synthesis by
      lung fibroblasts.
AB  - Asthma is a chronic lung disease characterized by local inflammation that can
      result in structural alterations termed airway remodeling. One component of
      airway remodeling involves fibroblast accumulation and activation, resulting in
      deposition of collagen I around small bronchi. Prostaglandin E(2) (PGE(2)) is the
      main eicosanoid lipid mediator produced by lung fibroblasts, and it exerts
      diverse anti-fibrotic actions. Dysregulation of the PGE(2) synthesis/response
      axis has been identified in human pulmonary fibrotic diseases and implicated in
      the pathogenesis of animal models of lung parenchymal fibrosis. Here we
      investigated the relationship between the fibroblast PGE(2) axis and airway
      fibrosis in an animal model of chronic allergic asthma. Airway fibrosis increased
      progressively as the number of airway challenges with antigen increased from 3 to
      7 to 12. Compared with cells from control lungs, fibroblasts grown from the lungs
      of asthmatic animals, regardless of challenge number, exhibited no defect in the
      ability of PGE(2) or its analogs to inhibit cellular proliferation and collagen I
      expression. This correlated with intact expression of the EP(2) receptor, which
      is pivotal for PGE(2) responsiveness. However, cytokine-induced upregulation of
      PGE(2) biosynthesis as well as expression of cyclooxygenase-2 (COX-2) and
      microsomal PGE synthase-1 declined with increasing numbers of antigen challenges.
      In addition, treatment with the COX-2-selective inhibitor nimesulide potentiated
      the degree of airway fibrosis following repeated allergen challenge. Because
      endogenous COX-2-derived PGE(2) acts as a brake on airway fibrosis, the inability
      of fibroblasts to upregulate PGE(2) generation in the inflammatory milieu
      presented by repeated allergen exposure could contribute to the airway remodeling
      and fibrosis observed in chronic asthma.

PMID- 21873452
TI  - A powerful and flexible statistical framework for testing hypotheses of allele
      specific gene expression from RNA-seq data.
AB  - Variation in gene expression is thought to make a significant contribution to
      phenotypic diversity among individuals within populations. Although high
      throughput cDNA sequencing offers a unique opportunity to delineate the genome
      wide architecture of regulatory variation, new statistical methods need to be
      developed to capitalize on the wealth of information contained in RNA-seq data
      sets. To this end, we developed a powerful and flexible hierarchical Bayesian
      model that combines information across loci to allow both global and locus
      specific inferences about allele-specific expression (ASE). We applied our
      methodology to a large RNA-seq data set obtained in a diploid hybrid of two
      diverse Saccharomyces cerevisiae strains, as well as to RNA-seq data from an
      individual human genome. Our statistical framework accurately quantifies levels
      of ASE with specified false-discovery rates, achieving high reproducibility
      between independent sequencing platforms. We pinpoint loci that show unusual and
      biologically interesting patterns of ASE, including allele-specific alternative
      splicing and transcription termination sites. Our methodology provides a
      rigorous, quantitative, and high-resolution tool for profiling ASE across whole
      genomes.

PMID- 21873453
TI  - Epigenetic regulation of normal human mammary cell type-specific miRNAs.
AB  - Epigenetic mechanisms are important regulators of cell type-specific genes,
      including miRNAs. In order to identify cell type-specific miRNAs regulated by
      epigenetic mechanisms, we undertook a global analysis of miRNA expression and
      epigenetic states in three isogenic pairs of human mammary epithelial cells
      (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated
      cell types typically present within a given organ, each with a distinct phenotype
      and a distinct epigenotype. While miRNA expression and epigenetic states showed
      strong interindividual concordance within a given cell type, almost 10% of the
      expressed miRNA showed a cell type-specific pattern of expression that was linked
      to the epigenetic state of their promoter. The tissue-specific miRNA genes were
      epigenetically repressed in nonexpressing cells by DNA methylation (38%) and
      H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic
      repression where both DNA methylation and H3K27me3 were present at their
      promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely
      related miRNA gene families can each display cell type-specific repression by the
      same or complementary epigenetic mechanisms, such as the MIR200 family, and
      MIR205, where fibroblasts repress MIR200C/141 by DNA methylation,
      MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3.
      Since deregulation of many of the epigenetically regulated miRNAs that we
      identified have been linked to disease processes such as cancer, it is predicted
      that compromise of the epigenetic control mechanisms is important for this
      process. Overall, these results highlight the importance of epigenetic regulation
      in the control of normal cell type-specific miRNA expression.

PMID- 21873454
TI  - Aquaporin 9 phosphorylation mediates membrane localization and neutrophil
      polarization.
AB  - Neutrophils are of prime importance in the host innate defense against invading
      microorganisms by using two primary mechanisms-locomotion toward and phagocytosis
      of the prey. Recent research points to pivotal roles for water channels known as
      AQPs in cell motility. Here, we focused on the role of AQP9 in chemoattractant
      induced polarization and migration of primary mouse neutrophils and neutrophil
      like HL60 cells. We found that AQP9 is phosphorylated downstream of fMLFR or PMA
      stimulation in primary human neutrophils. The dynamics of AQP9 were assessed
      using GFP-tagged AQP9 constructs and other fluorescent markers through various
      live-cell imaging techniques. Expression of WT or the phosphomimic S11D AQP9
      changed cell volume regulation as a response to hyperosmotic changes and enhanced
      neutrophil polarization and chemotaxis. WT AQP9 and S11D AQP9 displayed a very
      dynamic distribution at the cell membrane, whereas the phosphorylation-deficient
      S11A AQP9 failed to localize to the plasma membrane. Furthermore, we found that
      Rac1 regulated the translocation of AQP9 to the plasma membrane. Our results show
      that AQP9 plays an active role in neutrophil volume regulation and migration. The
      display of AQP9 at the plasma membrane depends on AQP9 phosphorylation, which
      appeared to be regulated through a Rac1-dependent pathway.

PMID- 21873455
TI  - Deletion of cannabinoid receptors 1 and 2 exacerbates APC function to increase
      inflammation and cellular immunity during influenza infection.
AB  - We and others have reported that simultaneous targeted deletion of CB(1) and
      CB(2) resulted in exacerbation of immune reactivity, suggesting a role of
      endocannabinoids in down-regulating immune function. In this study, we
      demonstrate that APC function is enhanced specifically in the absence of CB(1)
      and CB(2) signaling, resulting in an exacerbated immune response phenotype. After
      influenza infection, CB(1)(-/-)CB(2)(-/-) mice showed more pronounced pulmonary
      damage, increased inflammatory cell infiltrate, inflammation, and a greater
      cellular immune responses compared with WT mice, as evidenced by transcriptome
      analysis, more robust T cell activation, and effector cell cytokine production.
      After direct activation in vitro, there were no differences in the percentages of
      cytokine-producing CD4(+) T cells between CB(1)(-/-)CB(2)(-/-) and WT mice.
      However, untreated CB(1)(-/-)CB(2)(-/-) mice routinely had fewer naive T cells
      compared with WT, suggesting dysregulation of APC immune homeostasis. Moreover,
      bmDCs and AM isolated from CB(1)(-/-)CB(2)(-/-) mice exhibited a more mature
      phenotype, with and without TLR stimulation, and bmDCs elicited T cells more
      robustly than WT mice. Collectively, these findings implicate a role for CB(1)
      and CB(2) on APCs in regulating immune responses and immune homeostasis.

PMID- 21873458
TI  - Understanding impediments and enablers to physical activity among African
      American adults: a systematic review of qualitative studies.
AB  - Physical inactivity is a leading cause of premature death, disability and
      numerous chronic diseases. Minority and underserved populations in the United
      States and worldwide have a higher prevalence of physical inactivity affecting
      their morbidity and mortality rates. In the United States, African Americans are
      less physically active and have a higher proportion of many chronic diseases in
      comparison to Caucasians. This disparity needs to be well understood in order to
      design and implement effective interventions aimed at increasing physical
      activity levels among African Americans. In the present study, we conduct a
      systematic review (through 2010) of the qualitative literature pertaining to
      impediments and enablers to physical activity participation among African
      Americans. This review focuses on qualitative research due to its advantages in
      understanding attitudes and perceptions related to health behavior within the
      context of participants' natural environment. Findings are stratified by gender
      and age, to explore unique impediments and enablers based on age and sex and
      results are discussed within the socio-ecological model to account for the multi
      level nature of factors affecting physical activity. Findings should be taken
      into account by researchers, program planners and policymakers when tailoring
      physical activity interventions to African American communities in the United
      States.

PMID- 21873456
TI  - Differentiation of CD8+ T cells into effector cells is enhanced by physiological
      range hyperthermia.
AB  - In this study, we asked whether exposure to different physiologically relevant
      temperatures (33 degrees C, 37 degrees C, and 39.5 degrees C) could affect
      subsequent antigen-specific, activation-related events of naive CD8(+) T cells.
      We observed that temporary exposure of CD62L(hi)CD44(lo) Pmel-1 CD8(+) cells to
      39.5 degrees C prior to their antigen-dependent activation with gp100(25-33)
      peptide-pulsed C57BL/6 splenocytes resulted in a greater percentage of cells,
      which eventually differentiated into CD62L(lo)CD44(hi) effector cells compared
      with cells incubated at 33 degrees C and 37 degrees C. However, the proliferation
      rate of naive CD8(+) T cells was not affected by mild heating. While exploring
      these effects further, we observed that mild heating of CD8(+) T cells resulted
      in the reversible clustering of GM1(+) CD-microdomains in the plasma membrane.
      This could be attributable to a decrease in line tension in the plasma membrane,
      as we also observed an increase in membrane fluidity at higher temperatures.
      Importantly, this same clustering phenomenon was observed in CD8(+) T cells
      isolated from spleen, LNs, and peripheral blood following mild whole-body heating
      of mice. Further, we observed that mild heating also resulted in the clustering
      of TCRbeta and the CD8 coreceptor but not CD71R. Finally, we observed an enhanced
      rate of antigen-specific conjugate formation with APCs following mild heating,
      which could account for the difference in the extent of differentiation. Overall,
      these novel findings may help us to further understand the impact of
      physiologically relevant temperature shifts on the regulation of antigen-specific
      CD8(+) T cell activation and the subsequent generation of effector cells.

PMID- 21873457
TI  - Maternal KIR and fetal HLA-C: a fine balance.
AB  - NK cell effector function is regulated by a range of activating and inhibitory
      receptors, and many of their known ligands are MHC class I molecules. Human NK
      receptors encoded by the Killer immunoglobulin-like receptor (KIR) gene family
      recognize polymorphic HLA-C as well as some HLA-A and HLA-B molecules. KIRs are
      expressed by uterine NK (uNK) cells, which are distinctive NK cells directly in
      contact with the invading fetal placental cells that transform the uterine
      arteries during the first trimester. Trophoblast cells express both maternal and
      paternal HLA-C allotypes and can therefore potentially interact with KIRs
      expressed by uNK. Therefore, allorecognition of paternal HLA-C by maternal KIR
      might influence trophoblast invasion and vascular remodeling, with subsequent
      effects on placental development and the outcome of pregnancy. We discuss here
      the studies relating to KIR/HLA-C interactions with an emphasis on how these
      function during pregnancy to regulate placentation.

PMID- 21873459
TI  - Emotive computing may have a role in telecare.
AB  - This brief paper sets out arguments for the introduction of new technologies into
      telecare and lifestyle monitoring that can detect and monitor the emotive state
      of patients. The significantly increased use of computers by older people will
      enable the elements of emotive computing to be integrated with features such as
      keyboards and webcams, to provide additional information on emotional state. When
      this is combined with other data, there will be significant opportunities for
      system enhancement and the identification of changes in user status, and hence of
      need. The ubiquity of home computing makes the keyboard a very attractive,
      economic and non-intrusive means of data collection and analysis.

PMID- 21873460
TI  - Overexpression of Nrf2 protects cerebral cortical neurons from ethanol-induced
      apoptotic death.
AB  - Ethanol (ETOH) can cause apoptotic death of neurons by depleting GSH with an
      associated increase in oxidative stress. The current study illustrates a means to
      overcome this ETOH-induced neurotoxicity by enhancing GSH through boosting Nrf2,
      a transcription factor that controls GSH homeostasis. ETOH treatment caused a
      significant increase in Nrf2 protein, transcript expression, Nrf2-DNA binding
      activity, and expression of its transcriptional target, NQO1, in primary cortical
      neuron (PCNs). However, this increase in Nrf2 did not maintain GSH levels in
      response to ETOH, and apoptotic death still occurred. To elucidate this
      phenomenon, we silenced Nrf2 in neurons and found that ETOH-induced GSH depletion
      and the increase in superoxide levels were exacerbated. Furthermore, Nrf2
      knockdown resulted in significantly increased (P < 0.05) caspase 3 activity and
      apoptosis. Adenovirus-mediated overexpression of Nrf2 prevented ETOH-induced
      depletion of GSH from the medium and high GSH subpopulations and prevented ETOH
      related apoptotic death. These studies illustrate the importance of Nrf2
      dependent maintenance of GSH homeostasis in cerebral cortical neurons in the
      defense against oxidative stress and apoptotic death elicited by ETOH exposure.

PMID- 21873461
TI  - Plasticity and diversity of tRNA anticodon determinants of substrate recognition
      by eukaryotic A37 isopentenyltransferases.
AB  - The N(6)-(isopentenyl)adenosine (i(6)A) modification of some tRNAs at position
      A37 is found in all kingdoms and facilitates codon-specific mRNA decoding, but
      occurs in different subsets of tRNAs in different species. Here we examine
      yeasts' tRNA isopentenyltransferases (i.e., dimethylallyltransferase, DMATase,
      members of the Delta(2)-isopentenylpyrophosphate transferase, IPPT superfamily)
      encoded by tit1(+) in Schizosaccharomyces pombe and MOD5 in Saccharomyces
      cerevisiae, whose homologs are Escherichia coli miaA, the human tumor suppressor
      TRIT1, and the Caenorhabditis elegans life-span gene product GRO-1. A major
      determinant of miaA activity is known to be the single-stranded tRNA sequence,
      A36A37A38, in a stem-loop. tRNA(Trp)(CCA) from either yeast is a Tit1p substrate,
      but neither is a Mod5p substrate despite the presence of A36A37A38. We show that
      Tit1p accommodates a broader range of substrates than Mod5p. tRNA(Trp)(CCA) is
      distinct from Mod5p substrates, which we sort into two classes based on the
      presence of G at position 34 and other elements. A single substitution of C34 to
      G converts tRNA(Trp)(CCA) to a Mod5p substrate in vitro and in vivo, consistent
      with amino acid contacts to G34 in existing Mod5p-tRNA(Cys)(GCA) crystal
      structures. Mutation of Mod5p in its G34 recognition loop region debilitates it
      differentially for its G34 (class I) substrates. Multiple alignments reveal that
      the G34 recognition loop sequence of Mod5p differs significantly from Tit1p,
      which more resembles human TRIT1 and other DMATases. We show that TRIT1 can also
      modify tRNA(Trp)(CCA) consistent with broad recognition similar to Tit1p. This
      study illustrates previously unappreciated molecular plasticity and biological
      diversity of the tRNA-isopentenyltransferase system of eukaryotes.

PMID- 21873462
TI  - Facile synthesis of nucleoside 5'-(alpha-P-seleno)-triphosphates and
      phosphoroselenoate RNA transcription.
AB  - Phosphoroselenoate RNA (PSe-RNA) is nuclease resistant and has great potentials
      in X-ray crystal structure and function studies of noncoding RNAs and protein-RNA
      interactions. In order to conveniently synthesize PSe-RNA via transcription, we
      have developed a one-pot synthetic method for the nucleoside 5'-(alpha-P-seleno)
      triphosphates (NTPalphaSe) analogs without protecting any functionality of the
      ribonucleosides. The NTPalphaSe diastereomers have been purified, fully
      characterized, and incorporated into RNAs by T7 RNA polymerase. The transcribed
      RNAs are diastereomerically pure, and the Se-derivatized ribozymes are generally
      active. Furthermore, we have established an affinity purification strategy by
      using immobilized boronate to conveniently purify NTPalphaSe analogs. Though the
      affinity-purified NTPalphaSe analogs are diastereomeric mixtures, they can be
      directly used in transcription without a significant impact on the transcription
      efficiency. Moreover, we found that the PSe-nucleotide is stable during
      polyacrylamide gel purification, indicating that the PSe-RNAs can be purified
      straightforwardly for crystal structural and functional studies.

PMID- 21873464
TI  - Association of cardiac and non-cardiac chronic disease comorbidity on glycaemic
      control in a multi-ethnic population with type 1 and type 2 diabetes.
AB  - AIMS: To determine the prevalence of chronic disease comorbidity in south Asians
      (SAs) and white Europeans (WEs) with diabetes and to quantify the relationship of
      cardiac disease comorbidity (CDCM) and non-cardiac disease comorbidity (NCCM) to
      glycaemic control in SAs and WEs with type 1 and type 2 diabetes mellitus.
      METHODS: A cross-sectional study using a database of patients of SA (25.5%) and
      WE (74.5%) origin attending a specialist diabetes clinic in the UK between 2003
      and 2005 (n=5664). RESULTS: The prevalence of SAs and WEs with type 1 diabetes
      was 12% and 88%, respectively; for those with type 2 diabetes the prevalence was
      30% and 70%, respectively. Overall, the prevalence of comorbidity in people with
      type 1 diabetes was 25.5% and with type 2 diabetes was 47%. NCCM was more
      prevalent in WEs than SAs (17.6% vs 12.8%, p<0.001). In type 2 diabetes, the
      prevalence of suboptimal glycaemic control was significantly greater in SAs
      compared to WEs with NCCM and CDCM (79% vs 62%, p<0.001; 78% vs 65%, p<0.001,
      respectively). SAs with type 2 diabetes and comorbidity had excess odds of
      suboptimal glycaemic control compared to WEs: OR 2.27 (95% CI 1.50 to 3.43) for
      those with NCCM and OR 1.91 (95% CI 1.49 to 2.44) for those with CDCM.
      CONCLUSIONS: The prevalence of CDCM is higher in SAs compared to WEs with type 2
      diabetes, whereas the prevalence of NCCM is higher in WEs compared to SAs. Taking
      into account comorbidities, SAs (compared to WEs) with type 2 diabetes had an
      excess risk of having HbA1c >=7% ranging from 1.86- to 2.27-fold. Further
      research is needed to identify the reasons for unfavourable metabolic conditions
      in SAs and also develop and evaluate interventions.

PMID- 21873463
TI  - Prevalence of syn nucleobases in the active sites of functional RNAs.
AB  - Biological RNAs, like their DNA counterparts, contain helical stretches, which
      have standard Watson-Crick base pairs in the anti conformation. Most functional
      RNAs also adopt geometries with far greater complexity such as bulges, loops, and
      multihelical junctions. Occasionally, nucleobases in these regions populate the
      syn conformation wherein the base resides close to or over the ribose sugar,
      which leads to a more compact state. The importance of the syn conformation to
      RNA function is largely unknown. In this study, we analyze 51 RNAs with tertiary
      structure, including aptamers, riboswitches, ribozymes, and ribosomal RNAs, for
      number, location, and properties of syn nucleobases. These RNAs represent the set
      of nonoverlapping, moderate- to high-resolution structures available at present.
      We find that syn nucleobases are much more common among purines than pyrimidines,
      and that they favor C2'-endo-like conformations especially among those
      nucleobases in the intermediate syn conformation. Strikingly, most syn
      nucleobases participate in tertiary stacking and base-pairing interactions:
      Inspection of RNA structures revealed that the majority of the syn nucleobases
      are in regions assigned to function, with many syn nucleobases interacting
      directly with a ligand or ribozyme active site. These observations suggest that
      judicious placement of conformationally restricted nucleotides biased into the
      syn conformation could enhance RNA folding and catalysis. Such changes could also
      be useful for locking RNAs into functionally competent folds for use in X-ray
      crystallography and NMR.

PMID- 21873465
TI  - Overall patient satisfaction with hospitals: effects of patient-reported
      experiences and fulfilment of expectations.
AB  - BACKGROUND: Patient satisfaction and experiences are important parts of
      healthcare quality, but patient expectations are seldom included in quality
      assessments. The objective of this study was to estimate the effects of different
      predictors of overall patient satisfaction with hospitals, including patient
      reported experiences, fulfilment of patient expectations and socio-demographic
      variables. METHODS: Data were collected using a national patient-experience
      survey of 63 hospitals in the five health regions in Norway during the autumn of
      2006. Postal questionnaires were mailed to 24 141 patients after their discharge
      from hospital. Non-respondents were sent a reminder after 4 weeks. Multivariate
      linear regression analysis including multilevel regression was used to assess the
      predictors of overall patient satisfaction with hospitals. RESULTS: Thirteen
      variables were significantly associated with overall patient satisfaction: two
      variables about fulfilment of expectations, eight about patient-reported
      experiences and three socio-demographic variables. The regression model explained
      59% of the variation in overall patient satisfaction. The most important
      predictor of patient satisfaction with hospitals was patient-reported experiences
      with the nursing services (beta=0.27, p<0.001), followed by fulfilment of patient
      expectations (beta=0.21, p<0.001), experiences with doctor services (beta=0.12,
      p<0.001) and perceived incorrect treatment (beta=-0.12, p<0.001). Multilevel
      regression analysis confirmed most of the findings, but revealed that age was not
      a significant predictor of overall patient satisfaction. CONCLUSIONS: The study
      showed that both fulfilment of expectations and patient-reported experiences are
      distinct from but related to overall patient satisfaction. The most important
      predictors for overall patient satisfaction with hospitals are patient-reported
      experiences and fulfilment of expectations.

PMID- 21873467
TI  - Genetically engineered mouse models of pancreatic cancer: unravelling tumour
      biology and progressing translational oncology.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease despite
      tremendous scientific efforts. Numerous trials have failed to improve the outcome
      on this deadliest of all major cancers. Potential causes include a still
      insufficient understanding of key features of this cancer and imperfect
      preclinical models for identification of active agents and mechanisms of
      therapeutic responses and resistance. Modern genetically engineered mouse models
      of PDAC faithfully recapitulate the genetic and biological evolution of human
      PDAC, thereby providing a potentially powerful tool for addressing tumour
      biological issues as well as strategies for early detection and assessment of
      responses to therapeutic interventions. Here, the authors will discuss
      opportunities and challenges in the application of genetically engineered mouse
      models for translational approaches in pancreatic cancer and provide a non
      exhaustive list of examples with already existing or future clinical relevance.

PMID- 21873466
TI  - Viral clearance is associated with improved insulin resistance in genotype 1
      chronic hepatitis C but not genotype 2/3.
AB  - OBJECTIVES: Genotype-specific associations between hepatitis C virus (HCV) and
      insulin resistance (IR) have been described, but a causal relationship remains
      unclear. This study investigated the association between a sustained virological
      response (SVR) and IR after chronic HCV therapy. METHODS: 2255 treatment-naive
      patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials
      of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24
      weeks, respectively. IR was measured before treatment and 12 weeks after
      treatment using homeostasis model assessment (HOMA)-IR. RESULTS: Paired HOMA-IR
      measurements were available in 1038 non-diabetic patients (497 with genotype 1;
      541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in
      patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant
      reduction in the prevalence of IR in patients with genotype 1 achieving SVR
      (delta 10%; p<0.001), but not in genotype 1 non-responders or those with genotype
      2/3. Multivariate analysis indicated that SVR was associated with a significant
      reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those
      with genotype 2/3, which was independent of body mass index, alanine
      transaminase, gamma-glutamyl transpeptidase and lipid level changes. CONCLUSIONS:
      SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but
      not in those with genotype 2/3. Genotype 1 may have a direct effect on the
      development of IR, independent of host metabolic factors, and may be partially
      reversed by viral eradication.

PMID- 21873468
TI  - Cumulative incidence of metachronous colorectal cancer risk for mismatch repair
      gene mutation carriers is overestimated.

PMID- 21873469
TI  - Inhibition of histidine decarboxylase ablates the autocrine tumorigenic effects
      of histamine in human cholangiocarcinoma.
AB  - BACKGROUND: In several tumours the endogenous activity of histidine decarboxylase
      (HDC), the enzyme stimulating histamine synthesis, sustains the autocrine trophic
      effect of histamine on cancer progression. Cholangiocarcinoma is a biliary cancer
      with limited treatment options. Histamine interacts with four G-protein coupled
      receptors, H1-H4 histamine receptors (HRs). OBJECTIVE: To determine the effects
      of histamine stimulation and inhibition of histamine synthesis (by modulation of
      HDC) on cholangiocarcinoma growth. METHODS: In vitro studies were performed using
      multiple human cholangiocarcinoma lines. The expression levels of the histamine
      synthetic machinery and HRs were evaluated along with the effects of histamine
      stimulation and inhibition on cholangiocarcinoma proliferation. A xenograft
      tumour model was used to measure tumour volume after treatment with histamine or
      inhibition of histamine synthesis by manipulation of HDC. Vascular endothelial
      growth factor (VEGF) expression was measured in cholangiocarcinoma cells
      concomitant with the evaluation of the expression of CD31 in endothelial cells in
      the tumour microenvironment. RESULTS: Cholangiocarcinoma cells display (1)
      enhanced HDC and decreased monoamine oxidase B expression resulting in increased
      histamine secretion; and (2) increased expression of H1-H4 HRs. Inhibition of HDC
      and antagonising H1HR decreased histamine secretion in Mz-ChA-1 cells. Long-term
      treatment with histamine increased proliferation and VEGF expression in
      cholangiocarcinoma that was blocked by HDC inhibitor and the H1HR antagonist. In
      nude mice, histamine increased tumour growth (up to 25%) and VEGF expression
      whereas inhibition of histamine synthesis (by reduction of HDC) ablated the
      autocrine stimulation of histamine on tumour growth (~80%) and VEGF expression.
      No changes in angiogenesis (evaluated by changes in CD31 immunoreactivity) were
      detected in the in vivo treatment groups. CONCLUSION: The novel concept that an
      autocrine loop (consisting of enhanced histamine synthesis by HDC) sustains
      cholangiocarcinoma growth is proposed. Drug targeting of HDC may be important for
      treatment of patients with cholangiocarcinoma.

PMID- 21873470
TI  - 'Less education' is associated with use and sharing of antiretroviral medications
      for prophylaxis of HIV infection by US men who have sex with men.

PMID- 21873471
TI  - Unusual increase in reported HIV/AIDS cases among older persons in western Hunan
      province, China.

PMID- 21873472
TI  - Preclinical metabolism and disposition of SB939 (Pracinostat), an orally active
      histone deacetylase inhibitor, and prediction of human pharmacokinetics.
AB  - The preclinical absorption, distribution, metabolism, and excretion (ADME)
      properties of Pracinostat [(2E)-3-[2-butyl-1-[2-(diethylamino) ethyl]-1H
      benzimidazol-5-yl]-N-hydroxyarylamide hydrochloride; SB939], an orally active
      histone deacetylase inhibitor, were characterized and its human pharmacokinetics
      (PK) was predicted using Simcyp and allometric scaling. SB939 showed high aqueous
      solubility with high Caco-2 permeability. Metabolic stability was relatively
      higher in dog and human liver microsomes than in mouse and rat. The major
      metabolites formed in human liver microsomes were also observed in preclinical
      species. Human cytochrome P450 (P450) phenotyping showed that SB939 was primarily
      metabolized by CYP3A4 and CYP1A2. SB939 did not significantly inhibit human
      CYP3A4, 1A2, 2D6, and 2C9 (>25 MUM) but inhibited 2C19 (IC(50) = 5.8 MUM). No
      significant induction of human CYP3A4 and 1A2 was observed in hepatocytes. Plasma
      protein binding in mouse, rat, dog, and human ranged between ~84 and 94%. The
      blood-to-plasma ratio was ~1.0 in human blood. SB939 showed high systemic
      clearance (relative to liver blood flow) of 9.2, 4.5, and 1.5 l . h(-1) . kg(-1)
      and high volume of distribution at steady state (>0.6 l/kg) of 3.5, 1.7, and 4.2
      l/kg in mouse, rat, and dog, respectively. The oral bioavailability was 34, 65,
      and ~3% in mice, dogs, and rats, respectively. The predicted oral PK profile and
      parameters of SB939, using Simcyp and allometric scaling, were in good agreement
      with observed data in humans. Simcyp predictions showed lack of CYP3A4 and 2C19
      drug-drug interaction potential for SB939. In summary, the preclinical ADME of
      SB939 supported its preclinical and clinical development as an oral drug
      candidate.

PMID- 21873473
TI  - Implementation of a deidentified federated data network for population-based
      cohort discovery.
AB  - OBJECTIVE: The Cross-Institutional Clinical Translational Research project
      explored a federated query tool and looked at how this tool can facilitate
      clinical trial cohort discovery by managing access to aggregate patient data
      located within unaffiliated academic medical centers. METHODS: The project
      adapted software from the Informatics for Integrating Biology and the Bedside
      (i2b2) program to connect three Clinical Translational Research Award sites:
      University of Washington, Seattle, University of California, Davis, and
      University of California, San Francisco. The project developed an iterative
      spiral software development model to support the implementation and coordination
      of this multisite data resource. RESULTS: By standardizing technical
      infrastructures, policies, and semantics, the project enabled federated querying
      of deidentified clinical datasets stored in separate institutional environments
      and identified barriers to engaging users for measuring utility. DISCUSSION: The
      authors discuss the iterative development and evaluation phases of the project
      and highlight the challenges identified and the lessons learned. CONCLUSION: The
      common system architecture and translational processes provide high-level
      (aggregate) deidentified access to a large patient population (>5 million
      patients), and represent a novel and extensible resource. Enhancing the network
      for more focused disease areas will require research-driven partnerships
      represented across all partner sites.

PMID- 21873474
TI  - Two novel alkane hydroxylase-rubredoxin fusion genes isolated from a Dietzia
      bacterium and the functions of fused rubredoxin domains in long-chain n-alkane
      degradation.
AB  - Two alkane hydroxylase-rubredoxin fusion gene homologs (alkW1 and alkW2) were
      cloned from a Dietzia strain, designated DQ12-45-1b, which can grow on crude oil
      and n-alkanes ranging in length from 6 to 40 carbon atoms as sole carbon sources.
      Both AlkW1 and AlkW2 have an integral-membrane alkane monooxygenase (AlkB)
      conserved domain and a rubredoxin (Rd) conserved domain which are fused together.
      Phylogenetic analysis showed that these two AlkB-fused Rd domains formed a novel
      third cluster with all the Rds from the alkane hydroxylase-rubredoxin fusion gene
      clusters in Gram-positive bacteria and that this third cluster was distant from
      the known AlkG1- and AlkG2-type Rds. Expression of the alkW1 gene in DQ12-45-1b
      was induced when cells were grown on C(8) to C(32) n-alkanes as sole carbon
      sources, but expression of the alkW2 gene was not detected. Functional
      heterologous expression in an alkB deletion mutant of Pseudomonas fluorescens
      KOB2Delta1 suggested the alkW1 could restore the growth of KOB2Delta1 on C(14)
      and C(16) n-alkanes and induce faster growth on C(18) to C(32) n-alkanes than
      alkW1DeltaRd, the Rd domain deletion mutant gene of alkW1, which also caused
      faster growth than KOB2Delta1 itself. In addition, the artificial fusion of AlkB
      from the Gram-negative P. fluorescens CHA0 and the Rds from both Gram-negative P.
      fluorescens CHA0 and Gram-positive Dietzia sp. DQ12-45-1b significantly increased
      the degradation of C(32) alkane compared to that seen with AlkB itself. In
      conclusion, the alkW1 gene cloned from Dietzia species encoded an alkane
      hydroxylase which increased growth on and degradation of n-alkanes up to C(32) in
      length, with its fused rubredoxin domain being necessary to maintain the
      functions. In addition, the fusion of alkane hydroxylase and rubredoxin genes
      from both Gram-positive and -negative bacteria can increase the degradation of
      long-chain n-alkanes (such as C(32)) in the Gram-negative bacterium.

PMID- 21873475
TI  - Improvement in the thermostability of D-psicose 3-epimerase from Agrobacterium
      tumefaciens by random and site-directed mutagenesis.
AB  - The S213C, I33L, and I33L S213C variants of D-psicose 3-epimerase from
      Agrobacterium tumefaciens, which were obtained by random and site-directed
      mutagenesis, displayed increases of 2.5, 5, and 7.5 degrees C in the temperature
      for maximal enzyme activity, increases of 3.3-, 7.2-, and 29.9-fold in the half
      life at 50 degrees C, and increases of 3.1, 4.3, and 7.6 degrees C in apparent
      melting temperature, respectively, compared with the wild-type enzyme. Molecular
      modeling suggests that the improvement in thermostability in these variants may
      have resulted from increased putative hydrogen bonds and formation of new
      aromatic stacking interactions. The immobilized wild-type enzyme with and without
      borate maintained activity for 8 days at a conversion yield of 70% (350 g/liter
      psicose) and for 16 days at a conversion yield of 30% (150 g/liter psicose),
      respectively. After 8 or 16 days, the enzyme activity gradually decreased, and
      the conversion yields with and without borate were reduced to 22 and 9.6%,
      respectively, at 30 days. In contrast, the activities of the immobilized I33L
      S213C variant with and without borate did not decrease during the operation time
      of 30 days. These results suggest that the I33L S213C variant may be useful as an
      industrial producer of D-psicose.

PMID- 21873476
TI  - Spontaneous Gac mutants of Pseudomonas biological control strains: cheaters or
      mutualists?
AB  - Bacteria rely on a range of extracellular metabolites to suppress competitors,
      gain access to resources, and exploit plant or animal hosts. The GacS/GacA two
      component regulatory system positively controls the expression of many of these
      beneficial external products in pseudomonad bacteria. Natural populations often
      contain variants with defective Gac systems that do not produce most external
      products. These mutants benefit from a decreased metabolic load but do not appear
      to displace the wild type in nature. How could natural selection maintain the
      wild type in the presence of a mutant with enhanced growth? One hypothesis is
      that Gac mutants are "cheaters" that do not contribute to the public good,
      favored within groups but selected against between groups, as groups containing
      more mutants lose access to ecologically important external products. An
      alternative hypothesis is that Gac mutants have a mutualistic interaction with
      the wild type, so that each variant benefits by the presence of the other. In the
      biocontrol bacterium Pseudomonas chlororaphis strain 30-84, Gac mutants do not
      produce phenazines, which suppress competitor growth and are critical for biofilm
      formation. Here, we test the predictions of these alternative hypotheses by
      quantifying interactions between the wild type and the phenazine- and biofilm
      deficient Gac mutant within growing biofilms. We find evidence that the wild type
      and Gac mutants interact mutualistically in the biofilm context, whereas a
      phenazine-defective structural mutant does not. Our results suggest that the
      persistence of alternative Gac phenotypes may be due to the stabilizing role of
      local mutualistic interactions.

PMID- 21873477
TI  - Occurrence of intestinal and extraintestinal virulence genes in Escherichia coli
      isolates from rainwater tanks in Southeast Queensland, Australia.
AB  - In this study, 200 Escherichia coli isolates from 22 rainwater tank samples in
      Southeast Queensland, Australia, were tested for the presence of 20 virulence
      genes (VGs) associated with intestinal and extraintestinal pathotypes. In
      addition, E. coli isolates were also classified into phylogenetic groups based on
      the detection of the chuA, yjaA, and TSPE4.C2 genes. Of the 22 rainwater tanks, 8
      (36%) and 5 (23%) were positive for the eaeA (belonging to enteropathogenic E.
      coli [EPEC] and Shiga-toxigenic E. coli [STEC]) and ST1 (belonging to
      enterotoxigenic E. coli [ETEC]) genes, respectively. VGs (cdtB, cvaC, ibeA, kpsMT
      allele III, PAI, papAH, and traT) belonging to extraintestinal pathogenic E. coli
      (ExPEC) were detected in 15 (68%) of the 22 rainwater tanks. Of the 22 samples,
      17 (77%) and 11 (50%) contained E. coli belonging to phylogenetic groups A and
      B1, respectively. Similarly, 10 (45%) and 16 (72%) contained E. coli belonging to
      phylogenetic groups B2 and D, respectively. Of the 96 of the 200 strains from 22
      tanks that were VG positive, 40 (42%) were carrying a single VG, 36 (37.5%) were
      carrying two VGs, 17 (18%) were carrying three VGs, and 3 (3%) had four or more
      VGs. This study reports the presence of multiple VGs in E. coli strains belonging
      to the STEC, EPEC, ETEC, and ExPEC pathotypes in rainwater tanks. The public
      health risks associated with potentially clinically significant E. coli in
      rainwater tanks should be assessed, as the water is used for drinking and other,
      nonpotable purposes. It is recommended that rainwater be disinfected using
      effective treatment procedures such as filtration, UV disinfection, or simply
      boiling prior to drinking.

PMID- 21873478
TI  - Shotgun isotope array for rapid, substrate-specific detection of microorganisms
      in a microbial community.
AB  - The shotgun isotope array method has been proposed to be an effective new tool
      for use in substrate-specific microbe exploration without any prior knowledge of
      the community composition. Proof of concept was demonstrated by detection of
      acetate-degrading microorganisms in activated sludge and further verified by
      independent stable isotope probing (SIP).

PMID- 21873479
TI  - Evolution of secondary metabolite genes in three closely related marine
      actinomycete species.
AB  - The marine actinomycete genus Salinispora is composed of three closely related
      species. These bacteria are a rich source of secondary metabolites, which are
      produced in species-specific patterns. This study examines the distribution and
      phylogenetic relationships of genes involved in the biosynthesis of secondary
      metabolites in the salinosporamide and staurosporine classes, which have been
      reported for S. tropica and S. arenicola, respectively. The focus is on
      "Salinispora pacifica," the most recently discovered and phylogenetically diverse
      member of the genus. Of 61 S. pacifica strains examined, 15 tested positive for a
      ketosynthase (KS) domain linked to the biosynthesis of salinosporamide K, a new
      compound in the salinosporamide series. Compound production was confirmed in two
      strains, and the domain phylogeny supports vertical inheritance from a common
      ancestor shared with S. tropica, which produces related compounds in the
      salinosporamide series. There was no evidence for interspecies recombination
      among salA KS sequences, providing further support for the geographic isolation
      of these two salinosporamide-producing lineages. In addition, staurosporine
      production is reported for the first time for S. pacifica, with 24 of 61 strains
      testing positive for staD, a key gene involved in the biosynthesis of this
      compound. High levels of recombination were observed between staD alleles in S.
      pacifica and the cooccurring yet more distantly related S. arenicola, which
      produces a similar series of staurosporines. The distributions and phylogenies of
      the biosynthetic genes examined provide insight into the complex processes
      driving the evolution of secondary metabolism among closely related bacterial
      species.

PMID- 21873480
TI  - Groundwater seeps facilitate exposure to Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is a saprophytic bacterium which is the causative agent
      of melioidosis, a common cause of fatal bacterial pneumonia and sepsis in the
      tropics. The incidence of melioidosis is clustered spatially and temporally and
      is heavily linked to rainfall and extreme weather events. Clinical case
      clustering has recently been reported in Townsville, Australia, and has
      implicated Castle Hill, a granite monolith in the city center, as a potential
      reservoir of infection. Topsoil and water from seasonal groundwater seeps were
      collected around the base of Castle Hill and analyzed by quantitative real-time
      PCR targeting the type III secretion system genes for the presence of B.
      pseudomallei. The organism was identified in 65% (95% confidence interval [CI],
      49.5 to 80.4) of soil samples (n = 40) and 92.5% (95% CI, 83.9 to 100) of
      seasonal groundwater samples (n = 40). Further sampling of water collected from
      roads and gutters in nearby residential areas after an intense rainfall event
      found that 88.2% (95% CI, 72.9 to 100) of samples (n = 16) contained viable B.
      pseudomallei at concentrations up to 113 CFU/ml. Comparison of isolates using
      multilocus sequence typing demonstrated clinical matches and close associations
      between environmental isolates and isolates derived from clinical samples from
      patients in Townsville. This study demonstrated that waterborne B. pseudomallei
      from groundwater seeps around Castle Hill may facilitate exposure to B.
      pseudomallei and contribute to the clinical clustering at this site. Access to
      this type of information will advise the development and implementation of public
      health measures to reduce the incidence of melioidosis.

PMID- 21873481
TI  - Alga-derived substrates select for distinct Betaproteobacterial lineages and
      contribute to niche separation in Limnohabitans strains.
AB  - We examined the proportions of major Betaproteobacteria subgroups within
      bacterial communities in diverse nonaxenic, monospecific cultures of algae or
      cyanobacteria: four species of cryptophyta (genera Cryptomonas and Rhodomonas),
      four species of chlorophyta (genera Pediastrum, Staurastrum, and Chlamydomonas),
      and two species of cyanobacteria (genera Dolichospermum and Aphanizomenon). In
      the cryptophyta cultures, Betaproteobacteria represented 48 to 71% of total
      bacteria, the genus Limnohabitans represented 18 to 26%, and the Polynucleobacter
      B subcluster represented 5 to 16%. In the taxonomically diverse chlorophyta
      group, the genus Limnohabitans accounted for 7 to 45% of total bacteria. In
      contrast, cyanobacterial cultures contained significantly lower proportions of
      the Limnohabitans bacteria (1 to 3% of the total) than the cryptophyta and
      chlorophyta cultures. Notably, largely absent in all of the cultures was
      Polynucleobacter necessarius (Polynucleobacter C subcluster). Subsequently, we
      examined the growth of Limnohabitans strains in the presence of different algae
      or their extracellular products (EPP). Two strains, affiliated with Limnohabitans
      planktonicus and Limnohabitans parvus, were separately inoculated into axenic
      cultures of three algal species growing in an inorganic medium: Cryptomonas sp.,
      Chlamydomonas noctigama, and Pediastrum boryanum. The Limnohabitans strains
      cocultured with these algae or inoculated into their EPP consistently showed (i)
      pronounced population growth compared to the control without the algae or EPP and
      (ii) stronger growth stimulation of L. planktonicus than of L. parvus. Overall,
      growth responses of the Limnohabitans strains cultured with algae were highly
      species specific, which suggests a pronounced niche separation between two
      closely related Limnohabitans species likely mediated by different abilities to
      utilize the substrates produced by different algal species.

PMID- 21873482
TI  - Merging taxonomy with ecological population prediction in a case study of
      Vibrionaceae.
AB  - We synthesized population structure data from three studies that assessed the
      fine-scale distribution of Vibrionaceae among temporally and spatially distinct
      environmental categories in coastal seawater and animals. All studies used a
      dynamic model (AdaptML) to identify phylogenetically cohesive and ecologically
      distinct bacterial populations and their predicted habitats without relying on a
      predefined genetic cutoff or relationships to previously named species. Across
      the three studies, populations were highly overlapping, displaying similar
      phylogenetic characteristics (identity and diversity), and were predominantly
      congruent with taxonomic Vibrio species previously characterized as genotypic
      clusters by multilocus sequence analysis (MLSA). The environmental fidelity of
      these populations appears high, with 9 out of 12 reproducibly associating with
      the same predicted (micro)habitats when similar environmental categories were
      sampled. Overall, this meta-analysis provides information on the habitat
      predictability and structure of previously described species, demonstrating that
      MLSA-based taxonomy can, at least in some cases, serve to approximate
      ecologically cohesive populations.

PMID- 21873483
TI  - The microbial carbon pump: from genes to ecosystems.
AB  - The majority of marine dissolved organic carbon (DOC) is resistant to biological
      degradation and thus can remain in the water column for thousands of years,
      constituting carbon sequestration in the ocean. To date the origin of such
      recalcitrant DOC (RDOC) is unclear. A recently proposed conceptual framework, the
      microbial carbon pump (MCP), emphasizes the microbial transformation of organic
      carbon from labile to recalcitrant states. The MCP is concerned with both
      microbial uptakes and outputs of DOC compounds, covering a wide range from gene
      to ecosystem levels. In this minireview, the ATP binding cassette (ABC)
      transporter is used as an example for the microbial processing of DOC at the
      genetic level. The compositions of the ABC transporter genes of the two major
      marine bacterial clades Roseobacter and SAR11 demonstrate that they have distinct
      patterns in DOC utilization: Roseobacter strains have the advantage of taking up
      carbohydrate DOC, while SAR11 bacteria prefer nitrogen-containing DOC. At the
      ecosystem level, bacterially derived RDOC based on d-amino acid biomarkers is
      reported to be responsible for about a quarter of the total marine RDOC pool.
      Under future global warming scenarios, partitioning of primary production into
      DOC could be enhanced, and thus the MCP could play an even more important role in
      carbon sequestration by the ocean. Joint efforts to study the MCP from multiple
      disciplines are required to obtain a better understanding of ocean carbon cycle
      and its coupling with global change.

PMID- 21873484
TI  - Anatoxin-a synthetase gene cluster of the cyanobacterium Anabaena sp. strain 37
      and molecular methods to detect potential producers.
AB  - Cyanobacterial mass occurrences are common in fresh and brackish waters. They
      pose a threat to water users due to toxins frequently produced by the
      cyanobacterial species present. Anatoxin-a and homoanatoxin-a are neurotoxins
      synthesized by various cyanobacteria, e.g., Anabaena, Oscillatoria, and
      Aphanizomenon. The biosynthesis of these toxins and the genes involved in
      anatoxin production were recently described for Oscillatoria sp. strain PCC 6506
      (A. Mejean et al., J. Am. Chem. Soc. 131:7512-7513, 2009). In this study, we
      identified the anatoxin synthetase gene cluster (anaA to anaG and orf1; 29 kb) in
      Anabaena sp. strain 37. The gene (81.6% to 89.2%) and amino acid (78.8% to 86.9%)
      sequences were highly similar to those of Oscillatoria sp. PCC 6506, while the
      organization of the genes differed. Molecular detection methods for potential
      anatoxin-a and homoanatoxin-a producers of the genera Anabaena, Aphanizomenon,
      and Oscillatoria were developed by designing primers to recognize the anaC gene.
      Anabaena and Oscillatoria anaC genes were specifically identified in several
      cyanobacterial strains by PCR. Restriction fragment length polymorphism (RFLP)
      analysis of the anaC amplicons enabled simultaneous identification of three
      producer genera: Anabaena, Oscillatoria, and Aphanizomenon. The molecular methods
      developed in this study revealed the presence of both Anabaena and Oscillatoria
      as potential anatoxin producers in Finnish fresh waters and the Baltic Sea; they
      could be applied for surveys of these neurotoxin producers in other aquatic
      environments.

PMID- 21873486
TI  - Directed chromosomal integration and expression of the reporter gene gusA3 in
      Lactobacillus acidophilus NCFM.
AB  - Lactobacillus acidophilus NCFM is a probiotic microbe that survives passage
      through the human gastrointestinal tract and interacts with the host epithelium
      and mucosal immune cells. The potential for L. acidophilus to express antigens at
      mucosal surfaces has been investigated with various antigens and plasmid
      expression vectors. Plasmid instability and antibiotic selection complicate the
      possibility of testing these constructs in human clinical trials. Integrating
      antigen encoding genes into the chromosome for expression is expected to
      eliminate selection requirements and provide genetic stability. In this work, a
      reporter gene encoding a beta-glucuronidase (GusA3) was integrated into four
      intergenic chromosomal locations. The integrants were tested for genetic
      stability and GusA3 activity. Two locations were selected for insertion
      downstream of constitutively highly expressed genes, one downstream of slpA
      (LBA0169), encoding a highly expressed surface-layer protein, and one downstream
      of phosphopyruvate hydratase (LBA0889), a highly expressed gene with homologs in
      other lactic acid bacteria. An inducible location was selected downstream of lacZ
      (LBA1462), encoding a beta-galactosidase. A fourth location was selected in a low
      expression region. The expression of gusA3 was evaluated from each location by
      measuring GusA3 activity on 4-methyl-umbelliferyl-beta-d-glucuronide (MUG). GusA3
      activity from both highly expressed loci was more than three logs higher than the
      gusA3-negative parent, L. acidophilus NCK1909. GusA3 activity from the lacZ locus
      was one log higher in cells grown in lactose than in glucose. The differences in
      expression levels between integration locations highlights the importance of
      rational targeting with gene cassettes intended for chromosomal expression.

PMID- 21873488
TI  - Comparison of the gut microbiotas of healthy adult twins living in South Korea
      and the United States.
AB  - We compared the composition of the fecal microbiotas of Korean and U.S. adult
      twins. Our data indicated that the gut microbiota shows some signature of
      biogeography, potentially mediated by differences in diet and/or other
      environmental factors; however, these regional differences may be masked by other
      phenotypic variations, such as obesity.

PMID- 21873487
TI  - Identification and targeted cultivation of abundant novel freshwater
      sphingomonads and analysis of their population substructure.
AB  - Little is known with respect to bacterial population structures in freshwater
      environments. Using complementary culture-based, cloning, and high-throughput
      Illumina sequencing approaches, we investigated microdiverse clusters of bacteria
      that comprise members with identical or very similar 16S rRNA gene sequences. Two
      16S rRNA phylotypes could be recovered by cultivation in low-nutrient-strength
      liquid media from two lakes of different trophic status. Both phylotypes were
      found to be physiologically active in situ throughout most of the year, as
      indicated by the presence of their rRNA sequences in the samples. Analyses of
      internal transcribed spacer (ITS1) sequences revealed the presence of seven
      different sequence types among cultured representatives and the cloned rrn
      fragments. Illumina sequencing yielded 8,576 ITS1 sequences that encompassed 15
      major and numerous rare sequence types. The major ITS1 types exhibited distinct
      temporal patterns, suggesting that the corresponding Sphingomonadaceae lineages
      occupy different ecological niches. However, since strains of the same ITS1 type
      showed highly variable substrate utilization patterns, the potential mechanism of
      niche separation in Sphingomonadaceae cannot be explained by substrate
      utilization alone and may be related to other traits.

PMID- 21873485
TI  - Niche partitioning of marine group I Crenarchaeota in the euphotic and upper
      mesopelagic zones of the East China Sea.
AB  - Marine group I Crenarchaeota (MGI) represents a ubiquitous and numerically
      predominant microbial population in marine environments. An understanding of the
      spatial dynamics of MGI and its controlling mechanisms is essential for an
      understanding of the role of MGI in energy and element cycling in the ocean. In
      the present study, we investigated the diversity and abundance of MGI in the East
      China Sea (ECS) by analysis of crenarchaeal 16S rRNA gene, the ammonia
      monooxygenase gene amoA, and the biotin carboxylase gene accA. Quantitative PCR
      analyses revealed that these genes were higher in abundance in the mesopelagic
      than in the euphotic zone. In addition, the crenarchaeal amoA gene was positively
      correlated with the copy number of the MGI 16S rRNA gene, suggesting that most of
      the MGI in the ECS are nitrifiers. Furthermore, the ratios of crenarchaeal accA
      to amoA or to MGI 16S rRNA genes increased from the euphotic to the mesopelagic
      zone, suggesting that the role of MGI in carbon cycling may change from the
      epipelagic to the mesopelagic zones. Denaturing gradient gel electrophoretic
      profiling of the 16S rRNA genes revealed depth partitioning in MGI community
      structures. Clone libraries of the crenarchaeal amoA and accA genes showed both
      "shallow" and "deep" groups, and their relative abundances varied in the water
      column. Ecotype simulation analysis revealed that MGI in the upper ocean could
      diverge into special ecotypes associated with depth to adapt to the light
      gradient across the water column. Overall, our results showed niche partitioning
      of the MGI population and suggested a shift in their ecological functions between
      the euphotic and mesopelagic zones of the ECS.

PMID- 21873490
TI  - Relationship of serum fibroblast growth factor 23 with cardiovascular disease in
      older community-dwelling women.
AB  - OBJECTIVE: Although fibroblast growth factor 23 (FGF23) has been implicated in
      the pathogenesis of cardiovascular disease, the relationship between FGF23 and
      cardiovascular disease has not been well characterized in the general population.
      The aim of this study was to determine whether serum FGF23 is independently
      associated with cardiovascular disease in older community-dwelling women. DESIGN
      AND METHODS: A cross-sectional design was used to examine the relationship
      between serum FGF23 and cardiovascular disease. The subjects consisted of a
      population-based sample of 659 women, aged 70-79 years, who participated in the
      Women's Health and Aging Studies in Baltimore, Maryland. Prevalent cardiovascular
      disease (coronary heart disease, stroke, congestive heart failure, and peripheral
      artery disease) was assessed through diagnostic algorithms and physician
      adjudication. RESULTS: Of the 659 women, 185 (28.1%) had cardiovascular disease.
      Median (25th, 75th percentile) intact serum FGF23 was 34.6 (25.2, 46.2) pg/ml.
      The prevalence of cardiovascular disease in the lowest, middle, and highest
      tertile of serum FGF23 was 22.6, 24.9, and 36.7% respectively (P=0.002). Serum
      log FGF23 was associated with cardiovascular disease (odds ratio per 1 s.d.
      increase=1.23, 95% confidence interval 1.17, 1.30; P<0.0001) in a multivariable
      logistic regression model, adjusting for age, race, smoking, education, body mass
      index, cognition, diabetes, hypertension, physical activity, total cholesterol,
      high-density lipoprotein cholesterol, and renal function. CONCLUSION: Elevated
      serum FGF23 concentrations are independently associated with prevalent
      cardiovascular disease in older community-dwelling women. Further studies are
      needed to elucidate the potential biological mechanisms by which FGF23 may be
      involved in the pathogenesis of cardiovascular disease.

PMID- 21873492
TI  - Effects on transcription of mutations in ygjD, yeaZ, and yjeE genes, which are
      involved in a universal tRNA modification in Escherichia coli.
AB  - The Escherichia coli ygjD gene is critical for the universal tRNA modification
      N(6)-threonylcarbamoyladenosine, together with two other essential genes, yeaZ
      and yjeE. This study showed that the transcription of the thr and ilv operons in
      ygjD mutants was increased through the inhibition of transcription attenuation
      and that dnaG transcription was reduced.

PMID- 21873491
TI  - Expression during host infection and localization of Yersinia pestis
      autotransporter proteins.
AB  - Yersinia pestis CO92 has 12 open reading frames encoding putative conventional
      autotransporters (yaps), nine of which appear to produce functional proteins.
      Here, we demonstrate the ability of the Yap proteins to localize to the cell
      surface of both Escherichia coli and Yersinia pestis and show that a subset of
      these proteins undergoes processing by bacterial surface omptins to be released
      into the supernatant. Numerous autotransporters have been implicated in
      pathogenesis, suggesting a role for the Yaps as virulence factors in Y. pestis.
      Using the C57BL/6 mouse models of bubonic and pneumonic plague, we determined
      that all of these genes are transcribed in the lymph nodes during bubonic
      infection and in the lungs during pneumonic infection, suggesting a role for the
      Yaps during mammalian infection. In vitro transcription studies did not identify
      a particular environmental stimulus responsible for transcriptional induction.
      The primary sequences of the Yaps reveal little similarity to any characterized
      autotransporters; however, two of the genes are present in operons, suggesting
      that the proteins encoded in these operons may function together. Further work
      aims to elucidate the specific functions of the Yaps and clarify the
      contributions of these proteins to Y. pestis pathogenesis.

PMID- 21873493
TI  - Rational design of an artificial genetic switch: Co-option of the H-NS-repressed
      proU operon by the VirB virulence master regulator.
AB  - The H-NS protein represses the transcription of hundreds of genes in Gram
      negative bacteria. Derepression is achieved by a multitude of mechanisms, many of
      which involve the binding of a protein to DNA at the repressed promoter in a
      manner that compromises the maintenance of the H-NS-DNA nucleoprotein repression
      complex. The principal virulence gene promoters in Shigella flexneri, the cause
      of bacillary dysentery, are repressed by H-NS. VirB, a protein that closely
      resembles members of the ParB family of plasmid-partitioning proteins,
      derepresses the operons that encode the main structural components and the
      effector proteins of the S. flexneri type III secretion system. Bioinformatic
      analysis suggests that VirB has been co-opted into its current role as an H-NS
      antagonist in S. flexneri. To test this hypothesis, the potential for VirB to act
      as a positive regulator of proU, an operon that is repressed by H-NS, was
      assessed. Although VirB has no known relationship with the osmoregulated proU
      operon, it could relieve H-NS-mediated repression when the parS-like VirB binding
      site was placed appropriately upstream of the RpoD-dependent proU promoter. These
      results reveal the remarkable facility with which novel regulatory circuits can
      evolve, at least among those promoters that are repressed by H-NS.

PMID- 21873495
TI  - XoxF is required for expression of methanol dehydrogenase in Methylobacterium
      extorquens AM1.
AB  - In Gram-negative methylotrophic bacteria, the first step in methylotrophic growth
      is the oxidation of methanol to formaldehyde in the periplasm by methanol
      dehydrogenase. In most organisms studied to date, this enzyme consists of the
      MxaF and MxaI proteins, which make up the large and small subunits of this
      heterotetrameric enzyme. The Methylobacterium extorquens AM1 genome contains two
      homologs of MxaF, XoxF1 and XoxF2, which are ~50% identical to MxaF and ~90%
      identical to each other. It was previously reported that xoxF is not required for
      methanol growth in M. extorquens AM1, but here we show that when both xoxF
      homologs are absent, strains are unable to grow in methanol medium and lack
      methanol dehydrogenase activity. We demonstrate that these defects result from
      the loss of gene expression from the mxa promoter and suggest that XoxF is part
      of a complex regulatory cascade involving the 2-component systems MxcQE and
      MxbDM, which are required for the expression of the methanol dehydrogenase genes.

PMID- 21873494
TI  - Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster.
AB  - The mycobactin siderophore system is present in many Mycobacterium species,
      including M. tuberculosis and other clinically relevant mycobacteria. This
      siderophore system is believed to be utilized by both pathogenic and
      nonpathogenic mycobacteria for iron acquisition in both in vivo and ex vivo iron
      limiting environments, respectively. Several M. tuberculosis genes located in a
      so-called mbt gene cluster have been predicted to be required for the
      biosynthesis of the core scaffold of mycobactin based on sequence analysis. A
      systematic and controlled mutational analysis probing the hypothesized essential
      nature of each of these genes for mycobactin production has been lacking. The
      degree of conservation of mbt gene cluster orthologs remains to be investigated
      as well. In this study, we sought to conclusively establish whether each of nine
      mbt genes was required for mycobactin production and to examine the conservation
      of gene clusters orthologous to the M. tuberculosis mbt gene cluster in other
      bacteria. We report a systematic mutational analysis of the mbt gene cluster
      ortholog found in Mycobacterium smegmatis. This mutational analysis demonstrates
      that eight of the nine mbt genes investigated are essential for mycobactin
      production. Our genome mining and phylogenetic analyses reveal the presence of
      orthologous mbt gene clusters in several bacterial species. These gene clusters
      display significant organizational differences originating from an intricate
      evolutionary path that might have included horizontal gene transfers. Altogether,
      the findings reported herein advance our understanding of the genetic
      requirements for the biosynthesis of an important mycobacterial secondary
      metabolite with relevance to virulence.

PMID- 21873489
TI  - Relationships between free-living protozoa, cultivable Legionella spp., and water
      quality characteristics in three drinking water supplies in the Caribbean.
AB  - The study whose results are presented here aimed at identifying free-living
      protozoa (FLP) and conditions favoring the growth of these organisms and
      cultivable Legionella spp. in drinking water supplies in a tropical region.
      Treated and distributed water (+/-30 degrees C) of the water supplies of three
      Caribbean islands were sampled and investigated with molecular techniques, based
      on the 18S rRNA gene. The protozoan host Hartmannella vermiformis and cultivable
      Legionella pneumophila were observed in all three supplies. Operational taxonomic
      units (OTUs) with the highest similarity to the potential or candidate hosts
      Acanthamoeba spp., Echinamoeba exundans, E. thermarum, and an Neoparamoeba sp.
      were detected as well. In total, 59 OTUs of FLP were identified. The estimated
      protozoan richness did not differ significantly between the three supplies. In
      supply CA-1, the concentration of H. vermiformis correlated with the
      concentration of Legionella spp. and clones related to Amoebozoa predominated
      (82%) in the protozoan community. These observations, the low turbidity (<0.2
      nephelometric turbidity units [NTU]), and the varying ATP concentrations (1 to 12
      ng liter(-1)) suggest that biofilms promoted protozoan growth in this supply.
      Ciliophora represented 25% of the protozoan OTUs in supply CA-2 with elevated ATP
      concentrations (maximum, 55 ng liter(-1)) correlating with turbidity (maximum, 62
      NTU) caused by corroding iron pipes. Cercozoan types represented 70% of the
      protozoan clones in supply CA-3 with ATP concentrations of <1 ng liter(-1) and
      turbidity of <0.5 NTU in most samples of distributed water. The absence of H.
      vermiformis in most samples from supply CA-3 suggests that growth of this
      protozoan is limited at ATP concentrations of <1 ng liter(-1).

PMID- 21873496
TI  - Mesenteric lymph flow in adult and aged rats.
AB  - The objective of study was to evaluate the aging-associated changes, contractile
      characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in
      male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction
      amplitude, contraction frequency, and fractional pump flow, lymph flow velocity,
      wall shear stress, and minute active wall shear stress load were determined in
      MLV in vivo before and after N(omega)-nitro-L-arginine methyl ester hydrochloride
      (L-NAME) application at 100 MUM. The active pumping of the aged rat MLV in vivo
      was found to be severely depleted, predominantly through the aging-associated
      decrease in lymphatic contractile frequency. Such changes correlate with
      enlargement of aged MLV, which experienced much lower minute active shear stress
      load than adult vessels. At the same time, pumping in aged MLV in vivo may be
      rapidly increased back to levels of adult vessels predominantly through the
      increase in contraction frequency induced by nitric oxide (NO) elimination.
      Findings support the idea that in aged tissues surrounding the aged MLV, the
      additional source of some yet unlinked lymphatic contraction-stimulatory
      metabolites is counterbalanced or blocked by NO release. The comparative analysis
      of the control data obtained from experiments with both adult and aged MLV in
      vivo and from isolated vessel-based studies clearly demonstrated that ex vivo
      isolated lymphatic vessels exhibit identical contractile characteristics to
      lymphatic vessels in vivo.

PMID- 21873497
TI  - Impaired cardiac reserve and severely diminished skeletal muscle O2 utilization
      mediate exercise intolerance in Barth syndrome.
AB  - Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of
      exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of
      skeletal muscle O(2) extraction/utilization and 2) exercise intolerance in BTHS
      is related to impaired O(2) extraction/utilization, impaired cardiac function, or
      both. Participants with BTHS (age: 17 +/- 5 yr, n = 15) and control participants
      (age: 13 +/- 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer
      with continuous ECG and metabolic measurements. Echocardiography was performed at
      rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis
      muscle was continuously recorded for measurements of skeletal muscle O(2)
      extraction. Adjusting for age, peak O(2) consumption (16.5 +/- 4.0 vs. 39.5 +/-
      12.3 ml.kg(-1).min(-1), P < 0.001) and peak work rate (58 +/- 19 vs. 166 +/- 60
      W, P < 0.001) were significantly lower in BTHS than control participants. The
      percent increase from rest to peak exercise in ejection fraction (BTHS: 3 +/- 10
      vs. control: 19 +/- 4%, P < 0.01) was blunted in BTHS compared with control
      participants. The muscle tissue O(2) saturation change from rest to peak exercise
      was paradoxically opposite (BTHS: 8 +/- 16 vs. control: -5 +/- 9, P < 0.01), and
      the deoxyhemoglobin change was blunted (BTHS: 0 +/- 12 vs. control: 10 +/- 8, P <
      0.09) in BTHS compared with control participants, indicating impaired skeletal
      muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is
      due to both cardiac and skeletal muscle impairments that are consistent with
      cardiac and skeletal mitochondrial myopathy. These findings provide further
      insight to the pathophysiology of BTHS.

PMID- 21873498
TI  - Histone demethylase LSD1 deficiency during high-salt diet is associated with
      enhanced vascular contraction, altered NO-cGMP relaxation pathway, and
      hypertension.
AB  - Histone methylation, a determinant of chromatin structure and gene transcription,
      was thought to be irreversible, but recent evidence suggests that lysine-specific
      demethylase-1 (LSD1, Kdm1a) induces demethylation of histone H3 lysine 4 (H3K4)
      or H3K9 and thereby alters gene transcription. We previously demonstrated a human
      LSD1 phenotype associated with salt-sensitive hypertension. To test the
      hypothesis that LSD1 plays a role in the regulation of blood pressure (BP) via
      vascular mechanisms and gene transcription, we measured BP and examined vascular
      function and endothelial nitric oxide (NO) synthase (eNOS) expression in thoracic
      aorta of male wild-type (WT) and heterozygous LSD1 knockout mice (LSD1(+/-)) fed
      either a liberal salt (HS; 4% NaCl) or restricted salt diet (LS; 0.08% NaCl). BP
      was higher in LSD1(+/-) than WT mice on the HS diet but not different between
      LSD1(+/-) and WT mice on the LS diet. Further examination of the mechanisms of
      this salt-sensitive hypertension in LSD1(+/-) mice on the HS diet demonstrated
      that plasma renin activity and plasma levels and urinary excretion of aldosterone
      were less in LSD1(+/-) than WT, suggesting suppressed renin-angiotensin
      aldosterone system. In contrast, phenylephrine (Phe)-induced aortic contraction
      was greater in LSD1(+/-) than WT mice on the HS diet. Treatment of aortic rings
      with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a blocker of guanylate
      cyclase) enhanced Phe contraction in LSD1(+/-) compared with WT mice on the HS
      diet. Acetylcholine (Ach)-induced relaxation was less in LSD1(+/-) than WT mice
      on the HS diet. Endothelium removal or pretreatment with N(omega)-nitro-L
      arginine methyl ester (blocker of NOS) or ODQ abolished Ach-induced relaxation in
      aorta of WT but had minimal effect in LSD1(+/-). Vascular relaxation to sodium
      nitroprusside, an exogenous NO donor and guanylate cyclase activator, was
      decreased in LSD1(+/-) vs. WT mice on the HS diet. RT-PCR and Western blots
      revealed decreased eNOS mRNA expression and eNOS and guanylate cyclase protein in
      the heart and aorta of LSD1(+/-) compared with WT mice on HS diet. Thus, during
      the HS diet, LSD1 deficiency is associated with hypertension, enhanced vascular
      contraction, and reduced relaxation via NO-cGMP pathway. The data support a role
      for LSD1-mediated histone demethylation in the regulation of NOS/guanylate
      cyclase gene expression, vascular function, and BP during the HS diet.

PMID- 21873499
TI  - Early subclinical increase in pulmonary water content in athletes performing
      sustained heavy exercise at sea level: ultrasound lung comet-tail evidence.
AB  - Whether prolonged strenuous exercise performed by athletes at sea level can
      produce interstitial pulmonary edema is under debate. Chest sonography allows to
      estimate extravascular lung water, creating ultrasound lung comet-tail (ULC)
      artifacts. The aim of the study was to determine whether pulmonary water content
      increases in Ironmen (n = 31) during race at sea level and its correlation with
      cardiopulmonary function and systemic proinflammatory and cardiac biohumoral
      markers. A multiple factor analysis approach was used to determine the relations
      between systemic modifications and ULCs by assessing correlations among variables
      and groups of variables showing significant pre-post changes. All athletes were
      asymptomatic for cough and dyspnea at rest and after the race. Immediately after
      the race, a score of more than five comet tail artifacts, the threshold for a
      significant detection, was present in 23 athletes (74%; 16.3 +/- 11.2; P < 0.01
      ULC after the race vs. rest) but decreased 12 h after the end of the race (13
      athletes; 42%; 6.3 +/- 8.0; P < 0.01 vs. soon after the race). Multiple factor
      analysis showed significant correlations between ULCs and cardiac-related
      variables and NH(2)-terminal pro-brain natriuretic peptide. Healthy athletes
      developed subclinical increase in pulmonary water content immediately after an
      Ironman race at sea level, as shown by the increased number of ULCs related to
      cardiac changes occurring during exercise. Hemodynamic changes are one of several
      potential factors contributing to the mechanisms of ULCs.

PMID- 21873500
TI  - Temporal and spatial correlation of platelet-activating factor-induced increases
      in endothelial [Ca2+]i, nitric oxide, and gap formation in intact venules.
AB  - We have previously demonstrated that platelet-activating factor (PAF)-induced
      increases in microvessel permeability were associated with endothelial gap
      formation and that the magnitude of peak endothelial intracellular Ca(2+)
      concentration ([Ca(2+)](i)) and nitric oxide (NO) production at the single vessel
      level determines the degree of the permeability increase. This study aimed to
      examine whether the magnitudes of PAF-induced peak endothelial [Ca(2+)](i), NO
      production, and gap formation are correlated at the individual endothelial cell
      level in intact rat mesenteric venules. Endothelial gaps were quantified by the
      accumulation of fluorescent microspheres at endothelial clefts using confocal
      imaging. Endothelial [Ca(2+)](i) was measured on fura-2- or fluo-4-loaded
      vessels, and 4,5-diaminofluorescein (DAF-2) was used for NO measurements. The
      results showed that increases in endothelial [Ca(2+)](i), NO production, and gap
      formation occurred in all endothelial cells when vessels were exposed to PAF but
      manifested a spatial heterogeneity in magnitudes among cells in each vessel. PAF
      induced peak endothelial [Ca(2+)](i) preceded the peak NO production by 0.6 min
      at the cellular level, and the magnitudes of NO production and gap formation
      linearly correlated with that of the peak endothelial [Ca(2+)](i) in each cell,
      suggesting that the initial levels of endothelial [Ca(2+)](i) determine
      downstream NO production and gap formation. These results provide direct evidence
      from intact venules that inflammatory mediator-induced increases in microvessel
      permeability are associated with the generalized formation of endothelial gaps
      around all endothelial cells. The spatial differences in the molecular signaling
      that were initiated by the heterogeneous endothelial Ca(2+) response contribute
      to the heterogeneity in permeability increases along the microvessel wall during
      inflammation.

PMID- 21873501
TI  - New approaches in small animal echocardiography: imaging the sounds of silence.
AB  - Systolic and diastolic dysfunction of the left ventricle (LV) is a hallmark of
      most cardiac diseases. In vivo assessment of heart function in animal models,
      particularly mice, is essential to refining our understanding of cardiovascular
      disease processes. Ultrasound echocardiography has emerged as a powerful,
      noninvasive tool to serially monitor cardiac performance and map the progression
      of heart dysfunction in murine injury models. This review covers current
      applications of small animal echocardiography, as well as emerging technologies
      that improve evaluation of LV function. In particular, we describe speckle
      tracking imaging-based regional LV analysis, a recent advancement in murine
      echocardiography with proven clinical utility. This sensitive measure enables an
      early detection of subtle myocardial defects before global dysfunction in
      genetically engineered and rodent surgical injury models. Novel visualization
      technologies that allow in-depth phenotypic assessment of small animal models,
      including perfusion imaging and fetal echocardiography, are also discussed. As
      imaging capabilities continue to improve, murine echocardiography will remain a
      critical component of the investigator's armamentarium in translating animal data
      to enhanced clinical treatment of cardiovascular diseases.

PMID- 21873503
TI  - Non-invasive assessment of renal allograft fibrosis by dynamic sonographic tissue
      perfusion measurement.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) characterized by interstitial
      fibrosis and tubular atrophy is a major cause of renal transplant failure. The
      diagnosis can currently only be verified by a graft biopsy. PURPOSE: To evaluate
      whether non-invasive dynamic color Doppler sonographic parenchymal perfusion
      measurements are different in grafts with various degrees of biopsy proven renal
      transplant fibrosis. MATERIAL AND METHODS: Forty-nine adult patients were
      prospectively included. Four patients were excluded. Color Doppler videos from
      the renal cortex were recorded. Perfusion in the renal cortex was evaluated using
      a software package which calculates color pixel area and flow velocity, encoded
      by each pixel inside a region of interest of a video sequence. The software
      calculates parameters that describe tissue perfusion numerically. Two of these,
      the perfusion intensity and tissue pulsatility index, were compared to grade of
      interstitial fibrosis (0-3) in biopsies. Observer agreement was evaluated in a
      subset of 12 patients. RESULTS: Of the 45 patients analyzed, 18 patients had
      grade 0, 18 had grade 1, seven had grade 2 and two had grade 3 fibrosis. The mean
      perfusion intensity of grade 0 was significantly higher than that of grade 2 and
      3 fibrosis in the proximal cortical layer (1.65 m/s vs. 0.84 m/s, P = 0.008). No
      significant difference was found between grade 0 and grade 1 fibrosis. Perfusion
      intensity was correlated to estimated glomerular filtration rate (Pearson r 0.51,
      P = 0.001, R(2) = 0.26 and 0.46, P = 0.001, R(2) = 0.22 in the distal and
      proximal cortex, respectively). Inter-observer agreement of the perfusion
      intensity, expressed as intraclass correlation coefficient was 0.69 in the
      proximal part of the cortex. Intra-observer agreement was 0.85 for observer 1 and
      0.82 for observer 2. CONCLUSION: Perfusion intensity assessed by dynamic color
      Doppler measurements is significantly reduced in allografts with grade 2 and 3
      fibrosis compared to allografts without fibrosis. Further studies involving
      longitudinal assessment of allografts undergoing protocol biopsies would be of
      interest.

PMID- 21873502
TI  - Cardiac overexpression of 8-oxoguanine DNA glycosylase 1 protects mitochondrial
      DNA and reduces cardiac fibrosis following transaortic constriction.
AB  - Cardiac failure is associated with increased levels of oxidized DNA, especially
      mitochondrial (mtDNA). It is not known if oxidized mtDNA contributes to cardiac
      dysfunction. To test if protection of mtDNA can reduce cardiac injury, we
      produced transgenic mice with cardiomyocyte-specific overexpression of the DNA
      repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) isoform 2a. In one line of
      mice, the transgene increased OGG1 activity by 115% in mitochondria and by 28% in
      nuclei. OGG1 transgenic mice demonstrated significantly lower cardiac
      mitochondrial levels of the DNA guanine oxidation product 7,8-dihydro-8
      oxoguanine (8-oxo-dG) under basal conditions, after doxorubicin administration,
      or after transaortic constriction (TAC), but the transgene produced no detectable
      reduction in nuclear 8-oxo-dG content. OGG1 mice were tested for protection from
      the cardiac effects of TAC 13 wk after surgery. Compared with FVB-TAC mice,
      hearts from OGG1-TAC mice had lower levels of beta-myosin heavy chain mRNA but
      they did not display significant differences in the ratio of heart weight to
      tibia length or protection of cardiac function measured by echocardiography. The
      principle benefit of OGG1 overexpression was a significant decrease in TAC
      induced cardiac fibrosis. This protection was indicated by reduced Sirius red
      staining on OGG1 cardiac sections and by significantly decreased induction of
      collagen 1 and 3 mRNA expression in OGG1 hearts after TAC surgery. These results
      provide a new model to assess the damaging cardiac effects of 8-oxo-dG formation
      and suggest that increased repair of 8-oxo-dG in mtDNA decreases cardiac
      pathology.

PMID- 21873504
TI  - Observer variation for radiography, computed tomography, and magnetic resonance
      imaging of occult hip fractures.
AB  - BACKGROUND: Conventional radiography is insufficient for diagnosis in a small but
      not unimportant number of hip fractures, and secondary imaging with computed
      tomography (CT) or magnetic resonance imaging (MRI) is warranted. There are no
      convincing observer variation studies performed for conventional radiography or
      CT in occult fractures, and no large materials for MRI. PURPOSE: To assess
      observer variation in radiography, CT and MRI of suspected occult, non-displaced
      hip fractures, and to evaluate to what extent observer experience or patient age
      may influence observer performance. MATERIAL AND METHODS: A total of 375 patients
      after hip trauma where radiography was followed by CT or MRI to evaluate a
      suspected occult hip fracture were collected retrospectively from two imaging
      centers. After scoring by three observers with varying degrees of radiologic
      experience, observer variation was assessed by using linear weighted kappa
      statistics. RESULTS: For radiography, agreements between the three observers were
      moderate to substantial for intracapsular fractures, with kappa values in the
      ranges of 0.56-0.66. Kappa values were substantial for extracapsular fractures,
      in the ranges of 0.69-0.72. With increasing professional experience, fewer
      fractures were classified as equivocal at radiography. For CT and MRI, observer
      agreements were similar and almost perfect, with kappa values in the ranges of
      0.85-0.97 and 0.93-0.97. CONCLUSION: There were almost perfect observer
      agreements for CT and MRI in diagnosing non-displaced, occult hip fractures.
      Observer agreements for radiography were moderate to substantial, and observer
      experience influenced agreement only at radiography.

PMID- 21873505
TI  - The clinical significance and management of incidental focal FDG uptake in the
      thyroid gland on positron emission tomography/computed tomography (PET/CT) in
      patients with non-thyroidal malignancy.
AB  - BACKGROUND: Incidental focal fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG) uptake
      in the thyroid is not uncommon. A significant proportion is due to intercurrent
      thyroid cancer on further evaluation. PURPOSE: To investigate and discuss the
      clinical significance and management of incidental focal FDG uptake in the
      thyroid gland on positron emission tomography/computed tomography (PET/CT) in
      patients with non-thyroidal malignancy. MATERIAL AND METHODS: We investigated
      188/7896 (2.4%) patients who had incidental focal thyroid uptake on FDG PET/CT in
      an oncology population over a 45-month period. Diagnosis was confirmed in 63
      patients of whom 59 patients had histopathological verification. RESULTS: Thirty
      two percent of confirmed cases were malignant comprising intercurrent thyroid
      cancer in three-quarters of these patients. Maximum standardized uptake values of
      the thyroid lesions and SUV ratios compared with background thyroid and
      mediastinal uptake were not predictive of a benign or malignant etiology. In
      patients with incidental thyroid cancers, more than half had non-papillary and
      intermediate to high-risk pathology. CONCLUSION: Focal FDG uptake in the thyroid
      gland on PET/CT showed a malignancy risk of 32%. The intensity of uptake does not
      predict histology and underpins the importance of further investigations to
      exclude intercurrent thyroid cancer in suitable patients.

PMID- 21873506
TI  - Low-radiation-dose dual-phase MDCT protocol with split contrast media dose and
      time optimization: protocol design for renal donors evaluation.
AB  - BACKGROUND: A routine, multiphase, computed tomography (CT) protocol is
      associated with high radiation exposure to potential kidney donors. To reduce
      radiation exposure, several authors have suggested a reduction in the number of
      phases. PURPOSE: To evaluate a low-radiation-dose, dual-phase protocol (i.e. a
      protocol with an unenhanced phase and combined vascular and excretory phase) for
      the preoperative evaluation of potential renal donors. MATERIAL AND METHODS:
      Sixty-five potential renal donors were divided into two groups. The first group
      was scanned with a routine quadric-phase protocol (non-contrast, arterial,
      venous, and delayed), and the second group was scanned with a triple-phase
      protocol (dual phase protocol + venous phase). In the second group, we replaced
      CT angiography with a routine abdominal CT technique. In addition to the
      evaluation of renal arteries, veins, and excretory systems, the radiation dose of
      the suggested protocol was compared to that of the routine quadric-phase
      protocol. RESULTS: The suggested protocol was efficient in the evaluation of
      renal arteries, veins, and excretory systems in all studied potential renal
      donors. Renal arteries were well visualized in the combined vascular excretory
      phase using the routine abdominal CT technique; no significant difference was
      noted when these results were compared to those obtained from the CT angiography
      used in the quadric-phase protocol. The mean effective radiation dose of our
      suggested dual-phase protocol was only 34% of the dose resulting from the routine
      quadric-phase protocol. CONCLUSION: Use of a low-radiation, dual-phase, CT
      protocol, which relied on both an unenhanced phase and a combined vascular and
      excretory phase, significantly reduced radiation dose. Furthermore, the proposed
      protocol provides adequate visualization of renal arteries and veins, and affords
      sufficient opacification of the urinary tract using improved acquisition
      triggering.

PMID- 21873507
TI  - CT-guided biopsy of thoracic lesions with a novel wire-based needle guide device 
      initial experiences.
AB  - BACKGROUND: Biopsies guided by computed tomography (CT) play an important role in
      clinical practice. A short duration, minimal radiation dose and complication rate
      are of particular interest. Purpose To evaluate the potential of a novel self
      manufactured wire-based needle guide device for CT-guided thoracic biopsies with
      respect to radiation dose, intervention time and complication rate. MATERIAL AND
      METHODS: Forty patients that underwent CT-guided biopsies of thoracic lesions
      were included in this study and assigned to two groups. Patients in group A (n =
      20, mean age 69 +/- 8.4 years) underwent biopsies with a novel wire-based needle
      guide device, while patients in group B (n = 20, mean age 68.4 +/- 10.1 years)
      were biopsied without a needle guide device. The novel self-manufactured needle
      guide device consists of an iron/zinc wire modelled to a ring with a flexible arm
      and an eye at the end of the arm to stabilize the biopsy needle in the optimal
      position during intervention. Predefined parameters (radiation dose, number of
      acquired CT-slices, duration of intervention, complications) were compared
      between both groups. RESULTS: Mean radiation dose (CTDIvol 192 mGy versus 541
      mGy; P <= 0.001) and the number of acquired slices during intervention (n = 49 +/
      33 vs. n = 126 +/- 78; P <= 0.001) were significantly lower in group A compared
      with group B. Intervention time in group A (13.1 min) was significantly lower
      than in group B (18.5 min, P < 0.01). A pneumothorax as peri-interventional
      complication was observed less frequent after device assisted biopsies (n = 4 vs.
      n = 8, n.s.). CONCLUSION: The novel wire-based needle guide device is a promising
      tool to facilitate CT-guided thoracic biopsies reducing radiation dose,
      intervention time, and related complications. Further studies are mandatory to
      confirm these initial results.

PMID- 21873508
TI  - Dual energy CT for the assessment of reperfused chronic infarction - a
      feasibility study in a porcine model.
AB  - BACKGROUND: Detection of myocardial infarction has been the focus of considerable
      research over the past few decades. Recently developed dual source computed
      tomography (DSCT) scanners with dual energy mode have been used to detect
      myocardial infarction, but the studies on this topic are few. PURPOSE: To
      evaluate the feasibility and performance of dual energy CT (DECT) during arterial
      phase in coronary CT angiography for the detection of chronic infarction compared
      with late enhancement MRI (LE-MRI) and histopathology in a porcine model of
      reperfused myocardial infarction. MATERIAL AND METHODS: Myocardial infarctions
      were induced by 30 min occlusion of the proximal left anterior descending
      coronary artery in eight minipigs. DECT, post-contrast LE-MRI and histopathology
      were performed 60 days after infarct induction. The CT scan was performed in dual
      energy mode using a dedicated protocol. Myocardial iodine distribution was
      superimposed as color maps on grey scale multiplanar reformats of the heart. Two
      radiologists in consensus interpreted all imaging studies for presence of
      gadolinium uptake at LE-MRI reduced iodine content at DECT and hypoenhanced areas
      in the initial 100 kV coronary CT angiography images that were acquired during
      the DECT-acquisition. Results were compared with histopathology. RESULTS: Based
      on evaluable segments, DECT showed a sensitivity and specificity of 0.72 and
      0.88; LE-MRI showed a sensitivity and specificity of 0.78 and 0.92; and the 100
      kV data-set of the DECT scan showed a sensitivity and specificity of 0.60 and
      0.93, respectively, for the detection of histological proved ischemia.
      CONCLUSION: DECT during arterial phase coronary CT angiography, which is
      ordinarily used for coronary artery evaluation, is feasible for the detection of
      a chronic reperfused myocardial infarction.

PMID- 21873509
TI  - Step-and-shoot prospectively ECG-gated vs. retrospectively ECG-gated with tube
      current modulation coronary CT angiography using 128-slice MDCT patients with
      chest pain: diagnostic performance and radiation dose.
AB  - BACKGROUND: With increasing awareness for radiation exposure, the study of
      diagnostic accuracy of coronary CT angiography (CCTA) with low radiation dose
      techniques is mandatory to both radiologist and clinician. PURPOSE: To compare
      diagnostic performance and effective radiation dose between step-and-shoot
      prospectively ECG-gated and retrospectively ECG-gated with tube current
      modulation (TCM) CCTA using 128-slice multidetector computed tomography (MDCT).
      MATERIAL AND METHODS: We retrospectively evaluated 60 patients who underwent CCTA
      with either of two different low-dose techniques using 128-slice MDCT (23
      patients for step-and shoot-prospectively ECG-gated and 37 patients for
      retrospectively ECG-gated with TCM CCTA) followed by conventional coronary
      angiography. All coronary arteries and all segments thereof, except anatomical
      variants or small size (< 1.5 mm) ones, were included in analysis. RESULTS: In
      per-segment analysis, sensitivity, specificity, positive predictive value, and
      negative predictive value were 91/96%, 95/94%, 75/73%, and 98/99% for step-and
      shoot prospectively ECG-gated and retrospectively ECG gated with TCM CCTA,
      respectively, relative to conventional coronary angiography. Effective radiation
      dose were 1.75 +/- 0.83 mSv, 4.91 +/- 1.71 mSv in the step-and-shoot
      prospectively ECG-gated and retrospectively ECG-gated with TCM CCTA groups,
      respectively. CONCLUSION: The two low-radiation dose CCTA techniques using 128
      slice MDCT yields comparable diagnostic performance for coronary artery disease
      in symptomatic patients with low heart rates.

PMID- 21873511
TI  - RNA-binding protein Khd1 and Ccr4 deadenylase play overlapping roles in the cell
      wall integrity pathway in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae RNA-binding protein Khd1/Hek2 associates with
      hundreds of potential mRNA targets preferentially, including the mRNAs encoding
      proteins localized to the cell wall and plasma membrane. We have previously
      revealed that Khd1 positively regulates expression of MTL1 mRNA encoding a
      membrane sensor in the cell wall integrity (CWI) pathway. However, a khd1Delta
      mutation has no detectable phenotype on cell wall synthesis. Here we show that
      the khd1Delta mutation causes a severe cell lysis when combined with the deletion
      of the CCR4 gene encoding a cytoplasmic deadenylase. We identified the ROM2 mRNA,
      encoding a guanine nucleotide exchange factor (GEF) for Rho1, as a target for
      Khd1 and Ccr4. The ROM2 mRNA level was decreased in the khd1Delta ccr4Delta
      mutant, and ROM2 overexpression suppressed the cell lysis of the khd1Delta
      ccr4Delta mutant. We also found that Ccr4 negatively regulates expression of the
      LRG1 mRNA encoding a GTPase-activating protein (GAP) for Rho1. The LRG1 mRNA
      level was increased in the ccr4Delta and khd1Delta ccr4Delta mutants, and
      deletion of LRG1 suppressed the cell lysis of the khd1Delta ccr4Delta mutant. Our
      results presented here suggest that Khd1 and Ccr4 modulate a signal from Rho1 in
      the CWI pathway by regulating the expression of RhoGEF and RhoGAP.

PMID- 21873510
TI  - The Paf1 complex represses SER3 transcription in Saccharomyces cerevisiae by
      facilitating intergenic transcription-dependent nucleosome occupancy of the SER3
      promoter.
AB  - Previous studies have shown that repression of the Saccharomyces cerevisiae SER3
      gene is dependent on transcription of SRG1 from noncoding DNA initiating within
      the intergenic region 5' of SER3 and extending across the SER3 promoter region.
      By a mechanism dependent on the activities of the Swi/Snf chromatin remodeling
      factor, the HMG-like factor Spt2, and the Spt6 and Spt16 histone chaperones, SRG1
      transcription deposits nucleosomes over the SER3 promoter to prevent
      transcription factors from binding and activating SER3. In this study, we uncover
      a role for the Paf1 transcription elongation complex in SER3 repression. We find
      that SER3 repression is primarily dependent on the Paf1 and Ctr9 subunits of this
      complex, with minor contributions by the Rtf1, Cdc73, and Leo1 subunits. We show
      that the Paf1 complex localizes to the SRG1 transcribed region under conditions
      that repress SER3, consistent with it having a direct role in mediating SRG1
      transcription-dependent SER3 repression. Importantly, we show that the defect in
      SER3 repression in strains lacking Paf1 subunits is not a result of reduced SRG1
      transcription or reduced levels of known Paf1 complex-dependent histone
      modifications. Rather, we find that strains lacking subunits of the Paf1 complex
      exhibit reduced nucleosome occupancy and reduced recruitment of Spt16 and, to a
      lesser extent, Spt6 at the SER3 promoter. Taken together, our results suggest
      that Paf1 and Ctr9 repress SER3 by maintaining SRG1 transcription-dependent
      nucleosome occupancy.

PMID- 21873512
TI  - Description of Verrucosispora qiuiae sp. nov., isolated from mangrove swamp
      sediment, and emended description of the genus Verrucosispora.
AB  - A Micromonospora-like strain, RtIII47(T), was isolated from a mangrove swamp in
      Sanya, Hainan Province, China. Phylogenetic analysis based on the 16S rRNA gene
      sequence indicated that the strain had a close association with the genus
      Verrucosispora and shared the highest sequence similarity with Verrucosispora
      lutea YIM 013(T) (98.0%). The strain also showed high 16S rRNA gene sequence
      similarities to Micromonospora olivasterospora DSM 43868(T) (97.9%),
      Plantactinospora mayteni YIM 61359(T) (97.9%), Salinispora tropica CNB-440(T)
      (97.8%), Micromonospora peucetia DSM 43363(T) (97.7%), Micromonospora auratinigra
      TT1-11(T) (97.7%), Verrucosispora sediminis CGMCC 4.3550(T) (97.6%) and
      Salinispora arenicola CNH-643(T) (97.5%). Phylogenetic analysis based on the gyrB
      gene sequence supported the conclusion that strain RtIII47(T) should be assigned
      to the genus Verrucosispora. DNA-DNA relatedness between strain RtIII47(T) and
      the most closely related type strain, V. lutea YIM 013(T), was less than 40%.
      Chemotaxonomic results confirmed the taxonomic position of the isolate in the
      genus Verrucosispora, and revealed differences at the species level in polar
      lipids, whole-cell sugars and DNA G+C content. A combination of physiological and
      biochemical tests also distinguished this strain from other Verrucosispora
      species. Based on genotypic and phenotypic observations, strain RtIII47(T)
      (=CGMCC 4.5826(T) =NBRC 106684(T)) is proposed as the type strain of a novel
      species, Verrucosispora qiuiae sp. nov. An emended description of the genus
      Verrucosispora is also provided.

PMID- 21873513
TI  - Sphingomonas formosensis sp. nov., a polycyclic aromatic hydrocarbon-degrading
      bacterium isolated from agricultural soil.
AB  - In the present study, a yellow-pigmented, Gram-negative, short rod-shaped novel
      bacterium that was capable of degrading a wide range of polycyclic aromatic
      hydrocarbons (naphthalene, phenanthrene and pyrene) was isolated from
      agricultural soil located in Yunlin County, Taiwan. Comparative 16S rRNA gene
      sequence analysis positioned the novel strain in the genus Sphingomonas as an
      independent lineage adjacent to a subclade containing Sphingomonas fennica
      K101(T), Sphingomonas histidinilytica UM2(T), Sphingomonas wittichii RW1(T) and
      Sphingomonas haloaromaticamans A175(T). 16S rRNA gene sequence analysis of strain
      CC-Nfb-2(T) showed highest sequence similarity to S. fennica K101(T) (96.2%), S.
      histidinilytica UM2(T) (96.1%), S. wittichii RW1(T) (95.9%), S. haloaromaticamans
      A175(T) (95.7%), and Sphingobium ummariense RL-3(T) (94.7%); lower sequence
      similarities were observed with strains of all other Sphingomonas species. The
      strain contained phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylglycerol, sphingoglycolipid and diphosphatidylglycerol. The
      predominant fatty acids were summed feature 8 (C(18:1)omega7c and/or
      C(18:1)omega6c) C(16:0) and 11-methyl C(18:1)omega7c; C(14:0) 2-OH was the major
      2-hydroxy fatty acid. Previously, these lipids have been found to be
      characteristic of members of the genus Sphingomonas. The serine palmitoyl
      transferase gene (spt) was also detected and sphingolipid synthesis was
      confirmed. The predominant isoprenoid quinone system was ubiquinone (Q-10) and
      the isolate contained sym-homospermidine as the major polyamine. The DNA G+C
      content of the isolate was 62.8+/-0.8 mol%. On the basis of chemotaxonomic,
      phenotypic and phylogenetic data, strain CC-Nfb-2(T) represents a novel species
      within the genus Sphingomonas, for which the name Sphingomonas formosensis sp.
      nov. is proposed; the type strain is CC-Nfb-2(T) (=BCRC 80272(T)=DSM 24164(T)).

PMID- 21873514
TI  - Desulfobaculum xiamenensis gen. nov., sp. nov., a member of the family
      Desulfovibrionaceae isolated from marine mangrove sediment.
AB  - A taxonomic study was carried out on strain P1(T), which was isolated from
      mangrove sediment samples collected from Qinglan Port (Hainan, China). Cells were
      curved rods, that were motile, with a single polar flagellum. The strain was non
      spore-forming with a cell size of 0.6*1.5-2.2 um. Catalase and oxidase activities
      were not detected. Growth was observed in the temperature range 22-44  degrees C
      (optimum, 35-40  degrees C) and pH range 5.5-8.5 (optimum, pH 7.0). NaCl was
      required for growth and tolerated at up to 3.5% (w/v) (optimum, 0.5%). Strain
      P1(T) utilized hydrogen, succinate, L-malate, citrate, oxalate, DL-lactate,
      pyruvate, or cysteine as electron donors, and sulfate or sulfite as electron
      acceptors. Fermentation products from pyruvate were acetate, H(2) and CO(2).
      Phylogenetic analyses based on 16S rRNA gene sequences showed that strain P1(T)
      formed a distinct evolutionary lineage within the family Desulfovibrionaceae.
      Strain P1(T) was most closely related to members of the genera Desulfovibrio
      (92.0-94.3% 16S rRNA gene sequence similarity), Desulfocurvus (91.1%), Bilophila
      (87.9%) and Lawsonia (86.0%) of the family Desulfovibrionaceae. The DNA G+C
      content of strain P1(T) was 64.5 mol% and the major cellular fatty acids were iso
      C(15:0) (18.8%), anteiso-C(15:0) (5.0%), C(16:0) (14.2%) and iso-C(17:1)omega9c
      (24.4%). The predominant menaquinone was MK-7 (97%). Major polar lipids were
      phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol. Strain
      P1(T) was distinguishable from members of phylogenetically related genera by
      differences in several phenotypic properties. On the basis of the phenotypic and
      phylogenetic data, strain P1(T) represents a novel species of a new genus, for
      which the name Desulfobaculum xiamenensis gen. nov., sp. nov. is proposed. The
      type strain of Desulfobaculum xiamenensis is P1(T) (=CGMCC 1.5166(T)=DSM
      24233(T)).

PMID- 21873515
TI  - Sphingomonas endophytica sp. nov., isolated from Artemisia annua L.
AB  - A novel bacterium (strain YIM 65583(T)) belonging to the genus Sphingomonas was
      isolated from surface-sterilized tissue of Artemisia annua L., which was
      collected from Yunnan province, south-west China. Its morphology, physiology and
      biochemical features were consistent with those of members of the genus
      Sphingomonas. Analysis of the 16S rRNA gene sequence of strain YIM 65583(T)
      further confirmed that it should be classified as a member of the genus
      Sphingomonas and was most closely related to Sphingomonas phyllosphaerae FA2(T)
      (99.7%) and Sphingomonas yunnanensis YIM 003(T) (98.3%). The isolate was Gram
      negative and formed yellow-pigmented colonies on ISP 2 medium. It grew optimally
      at pH 6.0-8.0, at 20-37  degrees C and in the presence of 0-1% (w/v) NaCl. The
      major respiratory lipoquinone was ubiquinone-10; C(18:1)omega7c, anteiso-C(16:1),
      C(14:0)-2OH, C(17:1)omega6c, C(16:0) and C(15:0) were the major fatty acids.
      Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine and sphingoglycolipid. The G+C
      content of the genomic DNA was 63.3 mol%. The DNA-DNA relatedness values of the
      isolate YIM 65583(T) with S. phyllosphaerae FA2(T) and S. yunnanensis YIM 003(T)
      were 43.1% and 37.9%, respectively. Based on these features, it is concluded that
      the strain represents a novel species of the genus Sphingomonas, for which the
      name Sphingomonas endophytica sp. nov. is proposed, with YIM 65583(T) (=CCTCC AA
      209035(T)=JCM 17394(T)) as the type strain.

PMID- 21873516
TI  - Reply to: 'multiple sclerosis: variation of incidence of onset over time in the
      Faroe Islands'.

PMID- 21873518
TI  - Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3.
AB  - Lymphocyte activation gene-3 (LAG-3; CD223) is a CD4 homolog that is required for
      maximal regulatory T cell function and for the control of CD4(+) and CD8(+) T
      cell homeostasis. Lag3(-)(/)(-) NOD mice developed substantially accelerated
      diabetes with 100% incidence. Adoptive transfer experiments revealed that LAG-3
      was primarily responsible for limiting the pathogenic potential of CD4(+) T cells
      and, to a lesser extent, CD8(+) T cells. Lag3(-)(/)(-) mice exhibited
      accelerated, invasive insulitis, corresponding to increased CD4(+) and CD8(+) T
      cell islet infiltration and intraislet proliferation. The frequencies of islet Ag
      reactive chromogranin A-specific CD4(+) T cells and islet specific glucose-6
      phosphatase-specific CD8(+) T cells were significantly increased in the islets of
      Lag3(-)(/)(-) mice, suggesting an early expansion of pathogenic clones that is
      normally restrained by LAG-3. We conclude that LAG-3 is necessary for regulating
      CD4(+) and CD8(+) T cell function during autoimmune diabetes, and thus may
      contribute to limiting autoimmunity in disease-prone environments.

PMID- 21873520
TI  - IL-7 is required for the development of the intrinsic function of marginal zone B
      cells and the marginal zone microenvironment.
AB  - The characteristic microarchitecture of the marginal zone (MZ), formed by locally
      interacting MZ-specific B cells, macrophages, and endothelial cells, is critical
      for productive marginal zone B cell (MZB cell) Ab responses. Reportedly, IL-7
      deficient mice, although severely lymphopenic, retain small numbers of
      CD21(high)CD23(low) B cells consistent with MZB cell phenotype, suggesting that
      IL-7 signaling is not exclusively required for MZB cell lymphopoiesis. In this
      study, we investigated the function of IL-7(-/-) MZB cells and the IL-7(-/-)
      microenvironment using a model of hamster heart xenograft rejection, which
      depends exclusively on MZB cell-mediated production of T cell-independent IgM
      xenoantibodies (IgMXAb). C57BL/6-IL-7(-/-) mice accepted xenografts indefinitely
      and failed to produce IgMXAb, even after transfer of additional IL-7(-/-) or wild
      type C57BL/6 MZB cells. Transfer of wild-type but not IL-7(-/-) B cells enabled
      SCID mice to produce IgMXAb. When transferred to SCID mice, wild-type but not IL
      7(-/-) B cells formed B cell follicles with clearly defined IgM(+), MOMA-1(+),
      and MAdCAM-1(+) MZ structures. Conversely, adoptively transferred GFP(+) C57BL/6
      B cells homed to the MZ area in a SCID but not an IL-7(-/-) environment. Naive IL
      7(-/-) mice showed absent or aberrant splenic B cell structures. We provide
      evidence that IL-7 is critical for the development of the intrinsic function of
      MZB cells in producing rapidly induced IgM against T cell-independent type II
      Ags, for their homing potential, and for the development of a functional MZ
      microanatomy capable of attracting and lodging MZB cells.

PMID- 21873519
TI  - Foxp3+-inducible regulatory T cells suppress endothelial activation and leukocyte
      recruitment.
AB  - The ability of regulatory T cells (Treg) to traffic to sites of inflammation
      supports their role in controlling immune responses. This feature supports the
      idea that adoptive transfer of in vitro expanded human Treg could be used for
      treatment of immune/inflammatory diseases. However, the migratory behavior of
      Treg, as well as their direct influence at the site of inflammation, remains
      poorly understood. To explore the possibility that Treg may have direct anti
      inflammatory influences on tissues, independent of their well-established
      suppressive effects on lymphocytes, we studied the adhesive interactions between
      mouse Treg and endothelial cells, as well as their influence on endothelial
      function during acute inflammation. We show that Foxp3(+) adaptive/inducible Treg
      (iTreg), but not naturally occurring Treg, efficiently interact with endothelial
      selectins and transmigrate through endothelial monolayers in vitro. In response
      to activation by endothelial Ag presentation or immobilized anti-CD3epsilon,
      Foxp3(+) iTreg suppressed TNF-alpha- and IL-1beta-mediated endothelial selectin
      expression and adhesiveness to effector T cells. This suppression was contact
      independent, rapid acting, and mediated by TGF-beta-induced activin receptor-like
      kinase 5 signaling in endothelial cells. In addition, Foxp3(+) iTreg adhered to
      inflamed endothelium in vivo, and their secretion products blocked acute
      inflammation in a model of peritonitis. These data support the concept that
      Foxp3(+) iTreg help to regulate inflammation independently of their influence on
      effector T cells by direct suppression of endothelial activation and leukocyte
      recruitment.

PMID- 21873521
TI  - Modulation of IL-7 thresholds by SOCS proteins in developing B lineage cells.
AB  - During B lymphopoiesis, IL-7 induces survival, proliferation, and differentiation
      signals that are important during the pro-B to pre-B cell transition. We showed
      that murine small pre-B stage cells do not signal or proliferate in response to
      IL-7, yet they maintain IL-7R surface expression. Loss of proliferative
      responsiveness to IL-7 is mediated by suppressor of cytokine signaling protein 1
      (SOCS-1), the expression of which is regulated during B lymphopoiesis, with the
      highest levels observed in small pre-B cells. SOCS-1 inhibits IL-7 responses in
      pre-B cell lines and ex vivo B lineage cells. SOCS-1 expression and, thus,
      responsiveness to IL-7, can be regulated by IL-7 itself, as well as IFN-gamma and
      IL-21. Additionally, the transcriptional repressor Gfi-1b enhances the
      proliferative responsiveness of B cell lines to IL-7. We demonstrated that these
      molecules act together to form a SOCS-mediated "rheostat" that controls the level
      of IL-7R signaling in developing murine B lineage cells.

PMID- 21873522
TI  - Differential expression of the adaptor protein HSH2 controls the quantitative and
      qualitative nature of the humoral response.
AB  - Endogenous expression of the adaptor protein hematopoietic Src homology 2
      containing adaptor protein (HSH2) is regulated in a dynamic manner during B cell
      maturation and differentiation. Developing B cells lack detectable HSH2, whereas
      transitional 1 and 2 B cells in the periphery exhibit increasing levels of
      expression. Mature follicular B cells exhibit decreased expression of HSH2
      compared with transitional 2 B cells, and expression is further downregulated in
      germinal center B cells. In contrast, marginal zone B cells and B1a/b B cells
      exhibit high-level HSH2 expression. Regulation of HSH2 expression plays a
      critical role in determining the outcome of the humoral immune response as
      demonstrated using HSH2 transgenic (Tg) mice. Constitutive expression of HSH2 in
      the B lineage at levels comparable to B1a/b B cells results in decreased serum Ig
      titers for all subclasses with the exception of IgA. HSH2 Tg mice immunized with
      T-dependent or T-independent Ags exhibit a moderate decrease in the production of
      Ag-specific IgM, whereas class-switched isotypes are decreased by ~80-90%
      compared with control mice. Analysis of HSH2 Tg B cell activation in vitro
      demonstrated that HSH2 selectively regulates the B cell response to TNF family
      receptors (i.e., CD40 and BAFF-R), but not BCR- or TLR-dependent signals. These
      data demonstrate that changes in HSH2 expression have profound effects on the
      humoral immune response.

PMID- 21873523
TI  - An age-specific CD8+ T cell pathway that impairs the effectiveness of strategies
      to prolong allograft survival.
AB  - Age-related decline in immunity can impair cell-mediated responses during an
      infection, malignancy, and acute allograft rejection. Although much research has
      been allocated to understand the immune responses that impact the former two
      conditions, the cellular mechanisms by which aging impacts the immune acceptance
      of organ allografts are not completely clear. In this study, we examined how
      recipient age impacts the efficacy of therapies that modulate immune recognition
      of allografts using an immunogenic murine skin transplant model. We found that
      costimulatory blockade-based treatment failed to extend allograft survival in
      older recipients to the same extent as that observed in younger recipients.
      CD8(+) T cells were critical for the inability of aged recipients to achieve
      maximal allograft survival. Although aged mice displayed a larger number of
      effector memory T cells prior to transplantation, these cells did not exhibit
      enhanced alloreactivity compared with young memory T cells. In contrast, naive
      aged CD8(+) T cells exhibited enhanced IFN-gamma production to allostimulation
      compared with young naive T cells. Our results provide evidence that aging
      enhances CD8(+) T cell alloreactivity. This could impair the ability of
      costimulatory blockade-based therapies to prolong allograft survival. Thus,
      targeting CD8(+) T cells in humans may be a way to improve outcomes in older
      patients requiring immune modulatory therapy.

PMID- 21873524
TI  - Mutagenesis of beryllium-specific TCRs suggests an unusual binding topology for
      antigen recognition.
AB  - Unconventional Ags, such as metals, stimulate T cells in a very specific manner.
      To delineate the binding landscape for metal-specific T cell recognition, alanine
      screens were performed on a set of Be-specific TCRs derived from the lung of a
      chronic beryllium disease patient. These TCRs are HLA-DP2-restricted and express
      nearly identical TCR Vbeta5.1 chains coupled with different TCR alpha-chains.
      Site-specific mutagenesis of all amino acids comprising the CDRs of the TCRA and
      TCRB genes showed a dominant role for Vbeta5.1 residues in Be recognition, with
      little contribution from the TCR alpha-chain. Solvent-exposed residues along the
      alpha-helices of the HLA-DP2 alpha- and beta-chains were also mutated to alanine.
      Two beta-chain residues, located near the proposed Be binding site of HLA-DP2,
      played a dominant role in T cell recognition with no contribution from the HLA
      DP2 alpha-chain. These findings suggest that Be-specific T cells recognize Ag
      using an unconventional binding topology, with the majority of interactions
      contributed by TCR Vbeta5.1 residues and the HLA-DP2 beta1-chain. Thus, unusual
      docking topologies are not exclusively used by autoreactive T cells, but also for
      the recognition of unconventional metal Ags, such as Be.

PMID- 21873525
TI  - Virus-specific CD8+ T cells upregulate programmed death-1 expression during acute
      friend retrovirus infection but are highly cytotoxic and control virus
      replication.
AB  - It was recently reported that inhibitory molecules such as programmed death-1 (PD
      1) were upregulated on CD8(+) T cells during acute Friend retrovirus infection
      and that the cells were prematurely exhausted and dysfunctional in vitro. The
      current study confirms that most activated CD8(+) T cells upregulated expression
      of PD-1 during acute infection and revealed a dichotomy of function between PD
      1(hi) and PD-1(lo) subsets. More PD-1(lo) cells produced antiviral cytokines such
      as IFN-gamma and TNF-alpha, whereas more PD-1(hi) cells displayed characteristics
      of cytotoxic effectors such as production of granzymes and surface expression of
      CD107a. Importantly, CD8(+) T cells mediated rapid in vivo cytotoxicity and were
      critical for control of acute Friend virus replication. Thus, direct ex vivo
      analyses and in vivo experiments revealed high CD8(+) T cell functionality and
      indicate that PD-1 expression during acute infection is not a marker of T cell
      exhaustion.

PMID- 21873526
TI  - Glycogen synthase kinase-3 facilitates con a-induced IFN-gamma-- mediated immune
      hepatic injury.
AB  - Immune hepatic injury induced by Con A results primarily from IFN-gamma-mediated
      inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3,
      which acts proapoptotically and is proinflammatory, is also important for
      facilitating IFN-gamma signaling. We hypothesized a pathogenic role for GSK-3 in
      Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of
      C57BL/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic
      necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes,
      and deregulated expression of adhesion molecule CD54. Con A induced hepatic
      injury in an IFN-gamma receptor 1-dependent manner. Con A/IFN-gamma induced
      activation and expression of STAT1 in a GSK-3-dependent manner. GSK-3 facilitated
      IFN-gamma-induced inducible NO synthase, but had limited effects on CD95
      upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting
      GSK-3 decreased Con A-induced IFN-gamma production in both wild-type and IFN
      gamma receptor 1-deficient C57BL/6 mice. In Con A-activated NKT cells, GSK-3 was
      also activated and was required for nuclear translocation of T-box transcription
      factor Tbx21, a transcription factor of IFN-gamma, but it was not required for
      CD95 ligand expression or activation-induced cell death. These results
      demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by
      facilitating IFN-gamma-induced hepatopathy.

PMID- 21873527
TI  - IFN-gamma acts on the airway epithelium to inhibit local and systemic pathology
      in allergic airway disease.
AB  - Inhibiting allergic airway inflammation is the goal of therapy in persistent
      asthma. Administration of medication via the airways delivers drug directly to
      the site of inflammation and avoids systemic side effects but often fails to
      modulate systemic features of asthma. We have shown that Th1 cells, through
      production of IFN-gamma, inhibit many Th2-induced effector functions that promote
      disease. Using a newly generated mouse that expresses IFN-gammaR only on airway
      epithelial cells, we show that the airway epithelium controls a range of
      pathological responses in asthma. IFN-gamma acting only through the airway
      epithelium inhibits mucus, chitinases, and eosinophilia, independent of Th2 cell
      activation. IFN-gamma signaling through the airway epithelium inhibits eosinophil
      generation in the bone marrow, indicating that signals on the airway mucosal
      surface can regulate distant functions to inhibit disease. IFN-gamma actions
      through the airway epithelium will limit airway obstruction and inflammation and
      may be therapeutic in refractory asthma.

PMID- 21873528
TI  - Host immunity and pathogen strain contribute to intestinal disaccharidase
      impairment following gut infection.
AB  - Infection or other inflammatory insults in the small intestine often result in
      reduced disaccharidase enzyme levels. Using a mouse model of giardiasis, we
      examined the role of host immunity and pathogen virulence in mediating
      disaccharidase deficiency postinfection (p.i.). C57BL/6J mice were infected with
      two strains, WB and GS, of the human parasite Giardia duodenalis. The levels of
      sucrase, maltase, and lactase decreased in wild-type mice p.i. with the GS strain
      but not with the WB strain. Both CD4-deficient and SCID mice failed to eliminate
      the infection and did not exhibit disaccharidase deficiency. beta(2)
      Microglobulin knockout animals controlled infections similar to wild-type mice
      but exhibited no decrease in disaccharidase activity. Analysis of cytokine
      production by spleen and mesenteric lymph node cells showed production of IL-4,
      IL-10, IL-13, IL-17, IL-22, TNF-alpha, and IFN-gamma p.i. with both WB and GS,
      with IFN-gamma being the dominant cytokine for both parasite strains. Mesenteric
      lymph node cells produced lower levels of cytokines compared with splenocytes in
      response to parasite extract, although the overall pattern was similar. These
      data suggest that T cell responses mediate parasite clearance whereas also
      contributing to pathogenesis. They also demonstrate that differences in pathogen
      strain can also determine the outcome of infection and further our understanding
      of the clinical variation seen in human giardiasis.

PMID- 21873529
TI  - Mycophenolic acid differentially impacts B cell function depending on the stage
      of differentiation.
AB  - Production of pathogenic Abs contributes to disease progression in many
      autoimmune disorders. The immunosuppressant agent mycophenolic acid (MPA) has
      shown clinical efficacy for patients with autoimmunity. The goal of these studies
      was to elucidate the mechanisms of action of MPA on B cells isolated from healthy
      individuals and autoimmune patients. In this study, we show that MPA
      significantly inhibited both proliferation and differentiation of primary human B
      cells stimulated under various conditions. Importantly, MPA did not globally
      suppress B cell responsiveness or simply induce cell death, but rather
      selectively inhibited early activation events and arrested cells in the G0/G1
      phase of the cell cycle. Furthermore, MPA blocked expansion of both naive and
      memory B cells and prevented plasma cell (PC) differentiation and Ab production
      from healthy controls and individuals with rheumatoid arthritis. Finally, whereas
      MPA potently suppressed Ig secretion from activated primary B cells, terminally
      differentiated PCs were not susceptible to inhibition by MPA. The target of MPA,
      IMPDH2, was found to be downregulated in PCs, likely explaining the resistance of
      these cells to MPA. These results suggest that MPA provides benefit in settings
      of autoimmunity by directly preventing activation and PC differentiation of B
      cells; however, MPA is unlikely to impact autoantibody production by preexisting,
      long-lived PCs.

PMID- 21873530
TI  - ORAI1 deficiency impairs activated T cell death and enhances T cell survival.
AB  - ORAI1 is a pore subunit of Ca(2+) release-activated Ca(2+) channels that mediate
      TCR stimulation-induced Ca(2+) entry. A point mutation in ORAI1 (ORAI1(R91W))
      causes SCID in human patients that is recapitulated in Orai1(-/-) mice,
      emphasizing its important role in the immune cells. In this study, we have
      characterized a novel function of ORAI1 in T cell death. CD4(+) T cells from
      Orai1(-/-) mice showed robust proliferation with repetitive stimulations and
      strong resistance to stimulation-induced cell death due to reduced mitochondrial
      Ca(2+) uptake and altered gene expression of proapoptotic and antiapoptotic
      molecules (e.g., Fas ligand, Noxa, and Mcl-1). Nuclear accumulation of NFAT was
      severely reduced in ORAI1-deficient T cells, and expression of ORAI1 and a
      constitutively active mutant of NFAT recovered cell death. These results indicate
      NFAT-mediated cell death pathway as one of the major downstream targets of ORAI1
      induced Ca(2+) entry. By expressing various mutants of ORAI1 in wild-type and
      Orai1(-/-) T cells to generate different levels of intracellular Ca(2+), we have
      shown that activation-induced cell death is directly proportional to the
      intracellular Ca(2+) concentration levels. Consistent with the in vitro results,
      Orai1(-/-) mice showed strong resistance to T cell depletion induced by injection
      of anti-CD3 Ab. Furthermore, ORAI1-deficient T cells showed enhanced survival
      after adoptive transfer into immunocompromised hosts. Thus, our results
      demonstrate a crucial role of the ORAI1-NFAT pathway in T cell death and
      highlight the important role of ORAI1 as a major route of Ca(2+) entry during
      activated T cell death.

PMID- 21873531
TI  - An acquired defect in IgG-dependent phagocytosis explains the impairment in
      antibody-mediated cellular depletion in Lupus.
AB  - B cells play important roles in autoimmune diseases ranging from multiple
      sclerosis to rheumatoid arthritis. B cells have also long been considered central
      players in systemic lupus erythematosus. However, anti-CD20-mediated B cell
      depletion was not effective in two clinical lupus studies, whereas anti-B
      lymphocyte stimulator, which inhibits B cell survival, was effective. Others and
      we previously found that anti-CD20-based depletion was surprisingly ineffective
      in tissues of lupus-prone mice, but that persistent high doses eventually led to
      depletion and ameliorated lupus. Lupus patients might also have incomplete
      depletion, as suggested in several studies, and which could have led to
      therapeutic failure. In this study, we investigated the mechanism of resistance
      to Ab-mediated cellular depletion in murine lupus. B cells from lupus-prone mice
      were easily depleted when transferred into normal environments or in lupus-prone
      mice that lacked serum Ig. Serum from lupus-prone mice transferred depletion
      resistance, with the active component being IgG. Because depletion is FcgammaR
      dependent, we assayed macrophages and neutrophils exposed to lupus mouse serum,
      showing that they are impaired in IgG-mediated phagocytosis. We conclude that
      depletion resistance is an acquired, reversible phagocytic defect depending on
      exposure to lupus serum IgG. These results have implications for optimizing and
      monitoring cellular depletion therapy.

PMID- 21873532
TI  - Transcriptional regulation of SlPYL, SlPP2C, and SlSnRK2 gene families encoding
      ABA signal core components during tomato fruit development and drought stress.
AB  - In order to characterize the potential transcriptional regulation of core
      components of abscisic acid (ABA) signal transduction in tomato fruit development
      and drought stress, eight SlPYL (ABA receptor), seven SlPP2C (type 2C protein
      phosphatase), and eight SlSnRK2 (subfamily 2 of SNF1-related kinases) full-length
      cDNA sequences were isolated from the tomato nucleotide database of NCBI GenBank.
      All SlPYL, SlPP2C, and SlSnRK2 genes obtained are homologous to Arabidopsis
      AtPYL, AtPP2C, and AtSnRK2 genes, respectively. Based on phylogenetic analysis,
      SlPYLs and SlSnRK2s were clustered into three subfamilies/subclasses, and all
      SlPP2Cs belonged to PP2C group A. Within the SlPYL gene family, SlPYL1, SlPYL2,
      SlPYL3, and SlPYL6 were the major genes involved in the regulation of fruit
      development. Among them, SlPYL1 and SlPYL2 were expressed at high levels
      throughout the process of fruit development and ripening; SlPYL3 was strongly
      expressed at the immature green (IM) and mature green (MG) stages, while SlPYL6
      was expressed strongly at the IM and red ripe (RR) stages. Within the SlPP2C gene
      family, the expression of SlPP2C, SlPP2C3, and SlPP2C4 increased after the MG
      stage; SlPP2C1 and SlPP2C5 peaked at the B3 stage, while SlPP2C2 and SlPP2C6
      changed little during fruit development. Within the SlSnRK2 gene family, the
      expression of SlSnRK2.2, SlSnRK2.3, SlSnRK2.4, and SlSnRK2C was higher than that
      of other members during fruit development. Additionally, most SlPYL genes were
      down-regulated, while most SlPP2C and SlSnRK2 genes were up-regulated by
      dehydration in tomato leaf.

PMID- 21873533
TI  - Misery loves company: when sadness increases the desire for social connectedness.
AB  - In three experiments, the authors investigated the effects of sadness on the
      desire for social connectedness. They hypothesized that sadness serves an
      adaptive function by motivating people to reach out to others and preferentially
      attend to information related to one's current level of social connectedness, but
      only when it is instigated by social loss. Consistent with this hypothesis, the
      authors observed that sadness induced by an emotional depiction of social loss
      enhanced (a) attention to nonverbal cues, an important source of information
      concerning an individual's current level of social connectedness (Experiment 1),
      and (b) the desire to engage in social behaviors (Experiment 2). In Experiment 3
      the authors found that sadness that results from imagined social loss uniquely
      produced this pattern of effects. Sadness that resulted from imagined failure had
      different effects on motivation and no effect on sensitivity to nonverbal cues.
      These results support and refine functional explanations for the universality of
      sadness.

PMID- 21873534
TI  - Bayesian analysis of the effect of selection for residual feed intake on growth
      and feed intake curves in Yorkshire swine.
AB  - Gompertz growth functions were fitted to longitudinal measurements of daily feed
      intake (DFI) and BW of 586 boars and 495 gilts from a selection experiment in
      Yorkshire pigs for residual feed intake (RFI). The selection experiment consists
      of a line selected for low residual feed intake (LRFI) for 5 generations and a
      randomly selected control line (CTRL). The objectives of this study were to use
      Bayesian methods to estimate genetic parameters of the Gompertz curve parameters
      for DFI and BW, to evaluate the effect of selection for reduced RFI on the
      Gompertz parameters and shape of curves for DFI and BW, and to develop
      methodology for quantifying genetic variation at the level of the original
      phenotypes for DFI and BW based on the Bayesian analysis of the nonlinear model.
      Separate analyses were done for boars and gilts and for BW and DFI. A
      hierarchical model was specified in 2 levels: in the first level, the Gompertz
      function was modeled for each pig, and at the second level, a 3-trait linear
      mixed model was fitted to the 3 Gompertz parameters (asymptotic value, inflection
      point, and decay parameter), with fixed effects of line by generation and random
      effects of additive genetic and environmental effects. Bayesian methods were used
      to combine the 2 levels of modeling. A total of 30,000 random samples of the
      posterior distributions after convergence of Markov chains were used for
      inference. Posterior means of heritability within the first level of the model
      for the asymptotic value, inflection point, and decay parameter for DFI were
      0.74, 0.66, and 0.82 for boars and 0.79, 0.70, and 0.57 for gilts; corresponding
      estimates for BW were 0.64, 0.58, and 0.60 for boars and 0.46, 0.35, and 0.33 for
      gilts. For DFI, LRFI boars had a reduced mature DFI (2.91 vs. 3.20 kg/d) and an
      earlier inflection point (85 vs. 95 d) compared with CTRL boars. For BW, LRFI
      boars had a lighter mature BW (279 vs. 317 kg), an earlier inflection point (184
      vs. 198 d), and a decreased decay parameter (127 vs. 134 d) compared with CTRL
      boars. In contrast, LRFI gilts had a later inflection point (225 vs. 200 d) and a
      greater decay parameter (172 vs. 143 d) than CTRL gilts for BW. The other
      Gompertz curve parameters for DFI and BW for boars and gilts were considered not
      different between lines, with posterior probabilities of the line differences
      being greater than zero ranging from 0.1 to 0.9.

PMID- 21873535
TI  - Evaluation of 1-stage and 2-stage selection in yellow perch I: genetic and
      phenotypic parameters for body weight of F1 fish reared in ponds using
      microsatellite parentage assignment.
AB  - Two selection methods, 1-stage selection (OSS) and 2-stage selection (TSS), for
      improving efficiency and profitability of selective breeding of yellow perch were
      evaluated, through examining the genetic and phenotypic parameters for BW of F(1)
      fish using microsatellite parentage assignment in this study. Approximately 94%
      of the sampled yellow perch progeny were assigned to single parental pairs using
      8 microsatellite markers, which confirmed the applicability of the communal
      rearing technique in yellow perch breeding. Within OSS, the genetic correlation
      between 1-yr-BW and 2-yr-BW was high (0.98), indicating that the growth of yellow
      perch recorded at yr 1 could predict their growth for yr 2. Also mean family BW
      and family EBV for BW between yr 1 and 2 were found to be significantly
      correlated, suggesting yr 1 fast-growing yellow perch families continued to be
      the fast growing families in yr 2. Two-year random fish undergoing TSS were
      significantly heavier (P < 0.01) than those undergoing OSS. In addition, top
      males and females with TSS were heavier (P < 0.01) than those with OSS. Based on
      these results we concluded that the TSS was more desirable and effective for
      yellow perch breeding compared with OSS in terms of improving selection
      efficiency and reducing costs.

PMID- 21873536
TI  - Plasma concentrations of key metabolites and insulin in late-pregnant ewes
      carrying 1 to 5 fetuses.
AB  - Ewes bearing more than 1 fetus are more susceptible to pregnancy toxemia than
      those with a single fetus. Crossbreeding programs in Israel increased the
      occurrences of ewes bearing more than 2 fetuses; therefore, the aim was to assess
      the exacerbation in the metabolic status of ewes pregnant with several fetuses.
      Fifty ewes, genetically developed to achieve multiple-fetus pregnancies, were
      monitored, on average, from d 115 of pregnancy until lambing for plasma
      concentrations of several key metabolites and insulin. The numbers of fetuses
      were examined by ultrasonography at 35 d of pregnancy. Blood samples were
      collected weekly, and concentrations of glucose, beta-hydroxybutyrate (BHBA),
      NEFA, triglycerides, cholesterol, total calcium, and insulin were determined. The
      average litter size was 2.75 (+/-1.1), and 1 (1F), 2 (2F), 3 (3F), and 4 or more
      (4F) fetuses were conceived, respectively, by 6 (12%), 17 (34%), 14 (28%), and 13
      (26%) ewes. Total birth weights of lambs were 6.1, 9.5, 12.7, and 15.0 kg for 1F,
      2F, 3F, and 4F, respectively (P < 0.001). Plasma glucose concentrations in 1F
      were greater than those in 3F and 4F (P < 0.05) and were similar among 2F, 3F,
      and 4F. Trends toward increasing plasma concentrations of BHBA and NEFA were
      observed as the number of fetuses increased and also as lambing approached.
      Plasma concentrations of BHBA and NEFA were, respectively, 3.7 (P < 0.002) and
      2.1 (P < 0.001) times as great in 4F ewes as in 1F ewes. Trends toward decreased
      concentrations of triglycerides and cholesterol were observed as litter size
      increased. Insulin concentrations in blood decreased considerably as the numbers
      of fetuses increased and, on average, they were less by a factor of 5 in the 4F
      ewes than in the 1F ewes (P < 0.001). Moreover, insulin concentrations during the
      week before lambing were extremely low (e.g., 0.54 uIU/mL in the 4F ewes).
      Insulin concentrations were reduced in ewes bearing >3 fetuses, even 5 wk before
      lambing; this decline apparently began earlier than the last month of gestation.
      Therefore, it seems that insulin has a pivotal role in the etiology of pregnancy
      ketonemia in ewes carrying multiple fetuses. The present findings may suggest
      that the decline in insulin concentrations that apparently occurs in the earlier
      stages of pregnancy represents a homeorhetic control to spare glucose for the
      brains and fetoplacental units of the dams. The results clearly demonstrate the
      increased susceptibility to pregnancy toxemia of ewes carrying multiple fetuses.
      Appropriate nutritional strategies should be developed for ewes that conceive >3
      fetuses, to meet the increased nutritional requirements of the fetoplacental
      unit.

PMID- 21873537
TI  - Effect of ursodeoxycholic acid supplementation on growth, carcass
      characteristics, and meat quality of Wagyu heifers (Japanese Black cattle).
AB  - Ursodeoxycholic acid (UDCA), which is used as a hepatic and digestive medicine in
      humans and domestic animals, was added to the diet of Wagyu beef cattle to
      investigate its effects on growth, carcass characteristics, and meat quality. The
      study involved 20 Japanese Black heifers. Animals were divided into the following
      2 groups, a control group and a UDCA group (diet supplemented with UDCA), with
      each group containing 10 animals. The UDCA was administrated at a dose of 2.5
      g/(animal/d) to each heifer 24 times over a period of 7 mo in the finishing
      period. The heifers were slaughtered at 29 mo of age, and carcass characteristics
      and meat quality were determined. Both the UDCA group and the control group
      showed similar (P > 0.1) final BW, fattening periods, and daily BW gain.
      Supplementation of UDCA significantly increased meat quality grade (P < 0.05) and
      marbling (P < 0.01) and but did not show a significant (P > 0.1) effect on
      dressing percentage, fat thickness, rib thickness, or ribeye area. The percentage
      of ether extract in the LM was significantly greater (P < 0.05) in the UDCA group
      (43.2%) than in the control group (37.8%), whereas the percentage of moisture was
      significantly less in the former than the latter (P < 0.05).The L* (lightness)
      values of the muscles were greater (P < 0.05) in the UDCA group than in the
      control group. No significant differences (P > 0.1) were observed between groups
      in water-holding capacity, fatty acid composition, and vitamin E content of the
      LM or in intermuscular fat characteristics. Supplementation of the diet with UDCA
      can increase marbling without causing growth defects and can improve carcass
      characteristics in Wagyu cattle.

PMID- 21873538
TI  - Sulfur concentration in diets containing corn, soybean meal, and distillers dried
      grains with solubles does not affect feed preference or growth performance of
      weanling or growing-finishing pigs.
AB  - Four experiments were conducted to investigate the effects of distillers dried
      grains with solubles (DDGS) and dietary S on feed preference and performance of
      pigs. In a 10-d feed preference experiment (Exp. 1), 48 barrows (20.1 +/- 2.2 kg
      of BW) were randomly allotted to 3 treatment groups, with 8 replicate pens per
      treatment and 2 pigs per pen. A control diet based on corn and soybean meal, a
      DDGS diet containing 20% DDGS, and a DDGS-sulfur (DDGS-S) diet were prepared. The
      DDGS-S diet was similar to the DDGS diet with the exception that 0.74% CaSO(4)
      was added to the diet. Two diets were provided in separate feeders in each pen:
      1) the control diet and the DDGS diet, 2) the control diet and the DDGS-S diet,
      or 3) the DDGS diet and the DDGS-S diet. Preference for the DDGS diet and the
      DDGS-S diet vs. the control diet was 35.2 and 32.6%, respectively (P < 0.05), but
      there was no difference between the DDGS diet and the DDGS-S diet. In Exp. 2, a
      total of 90 barrows (10.3 +/- 1.4 kg of BW) were allotted to 3 treatments, with
      10 replicate pens and 3 pigs per pen, and were fed the diets used in Exp. 1 for
      28 d, but only 1 diet was provided per pen. Pigs fed the control diet gained more
      BW (497 vs. 423 and 416 g/d; P < 0.05) and had greater G:F (0.540 vs. 0.471 and
      0.455; P < 0.05) than pigs fed the DDGS or the DDGS-S diet, but no differences
      between the DDGS and the DDGS-S diets were observed. In a 10-d feed preference
      experiment (Exp. 3), 30 barrows (49.6 +/- 2.3 kg of BW) were allotted to 3
      treatment groups, with 10 replicates per group. The experimental procedures were
      the same as in Exp. 1, except that 30% DDGS was included in the DDGS and DDGS-S
      diets and 1.10% CaSO(4) was added to the DDGS-S diet. Feed preference for the
      DDGS and the DDGS-S diets, compared with the control diet, was 29.8 and 32.9%,
      respectively (P < 0.01), but there was no difference between the DDGS and the
      DDGS-S diets. In Exp. 4, a total of 120 barrows (34.2 +/- 2.3 kg of BW) were fed
      grower diets for 42 d and finisher diets for 42 d. Diets were formulated as in
      Exp. 3. Pigs on the control diets gained more BW (1,021 vs. 912 and 907 g/d; P <
      0.05) and had greater G:F (0.335 vs. 0.316 and 0.307; P < 0.05) than pigs fed the
      DDGS or DDGS-S diet, respectively, but no differences between pigs fed the DDGS
      and the DDGS-S diets were observed. In conclusion, dietary S concentration does
      not negatively affect feed preference, feed intake, or growth performance of
      weanling or growing-finishing pigs fed diets based on corn, soybean meal, and
      DDGS.

PMID- 21873539
TI  - Effects of maternal plane of nutrition and increased dietary selenium in first
      parity ewes on inflammatory response in the ovine neonatal gut.
AB  - Many areas of the western United States have soils that have increased Se
      content, and ruminants grazing these rangelands may ingest increased quantities
      of Se. In addition, high-energy diets or increased Se intake may induce gut
      inflammation. The objective of this study was to evaluate the effects of maternal
      plane of nutrition and increased dietary Se during gestation on inflammatory
      responses in neonatal lamb ileal tissue, a major immune organ. Rambouillet ewes
      (age = 240 +/- 17 d; initial BW = 52.1 +/- 6.2 kg) were allocated to 4 treatments
      arranged in a 2 * 2 factorial. Factors included Se [adequate Se (ASe, 11.5 ug/kg
      of BW) or high Se (HSe, 77.0 ug/kg of BW)] initiated at breeding, and nutritional
      plane [100% (CON) or 140% (HIH) of requirements] initiated at d 40 of gestation.
      Ewes were fed individually from d 40, and lambs were removed at parturition and
      fed artificial colostrum and milk replacer. Lambs were necropsied at 20 d of age,
      and ileal tissues were sampled for immunoblotting and real-time quantitative
      reverse-transcription PCR analyses. The ASe-HIH and HSe-CON treatments had no
      effect (P = 0.179) on inflammatory signaling compared with ASe-CON. However,
      greater inflammatory signaling was detected in the HSe-HIH group, as shown by
      increased (P < 0.05) mRNA expression of tumor necrosis factor-alpha and
      chemotaxis IL-8. Consistently, phosphorylation of c-Jun N-terminal kinase, a
      primary inflammatory signaling mediator, was greater (P < 0.05) in the HSe-HIH
      group compared with other treatments. Consistent with cytokine expression, mast
      cell density was less in the HSe-CON group than in other treatments. The
      expression of transforming growth factor beta mRNA was greater (P < 0.05) in the
      HSe-HIH group; consistently, collagen content was increased in the HSe-HIH group
      compared with the ASe-CON group (P < 0.05). In conclusion, independently, neither
      HSe nor HIH had major effects on inflammation, but in combination, these maternal
      treatments induced an inflammatory response in the neonatal intestine.

PMID- 21873540
TI  - Effect of graded levels of niacin supplementation of a semipurified diet on
      energy and nitrogen balance, growth performance, diarrhea occurrence, and niacin
      metabolite excretion by growing swine.
AB  - Thirty-six crossbred barrows with an average initial age of 42 d and BW of 13.8
      kg were placed in individual metabolism crates in a 35-d experiment to evaluate
      the supplementation of a semipurified diet with graded levels of crystalline
      niacin. Response criteria were energy and N balance, growth performance,
      occurrence of niacin deficiency diarrhea, and urinary excretion of the niacin
      metabolite N(1)-methyl-2-pyridone-5-carboxylamide (PYR). The basal diet met the
      true ileal Trp requirement of growing swine, and supplementation with 6, 10, 14,
      18, 22, or 44 mg of niacin/kg made 6 treatments. Pigs were observed for scours
      twice daily, and pig BW and feed consumption were determined weekly. Total urine
      collections and fecal grab samples were made twice daily from each pig from d 28
      to 35. Pigs fed the diet containing 14 mg of niacin/kg absorbed and retained more
      (P < 0.05) grams of N/d, had a greater N digestibility (%, P < 0.05), a greater
      ADFI and ADG (P < 0.10), and no diarrhea (P < 0.05) compared with pigs fed the
      diet containing 6 mg of niacin/kg, and pigs fed the diet containing 10 mg of
      niacin/kg were intermediate in ADG. There were no additional improvements in the
      response criteria with niacin supplementation greater than 14 mg/kg. Urinary PYR
      criteria (mg/L and mg/d) were greater (P < 0.001) for pigs fed the diet
      containing 44 mg of niacin/kg than for pigs fed the diets containing 6 to 22 mg
      of niacin/kg. However, urinary PYR criteria for pigs fed the diets containing 6
      to 22 mg of niacin/kg did not differ from each other, indicating that PYR was not
      a sensitive indicator of niacin status for growing swine. Niacin treatment did
      not affect the percentages of N retained/N absorbed, N retained/N intake, DE, or
      ME. In conclusion, 14 mg of crystalline niacin/kg of semipurified diet adequate
      in Trp was the minimum concentration of niacin that maximized N utilization and
      growth performance, and prevented niacin deficiency diarrhea of growing swine in
      the current experiment. Because practical feed ingredients may be sources of
      available endogenous niacin, supplementation of practical diets with 100% of the
      current NRC requirement for niacin should provide adequate niacin for growing
      swine.

PMID- 21873541
TI  - Effect of split marketing on the welfare, performance, and carcass traits of
      finishing pigs.
AB  - The aim of this study was to compare a split marketing (SM) strategy, in which
      the heaviest pigs in a group are removed and slaughtered earlier than the others,
      with an all-out (AO) marketing strategy, in which all pigs are removed from the
      pen simultaneously and slaughtered on the same day, in terms of welfare,
      performance, and carcass traits of noncastrated (i.e., intact) male and female
      pigs. The experimental treatments were arranged in a 2 * 2 factorial array with
      1) marketing strategy (SM vs. AO) and 2) sex (males vs. females), which yielded 4
      treatment groups of 14 pigs (73.1 +/- 4.8 kg): male SM, male AO, female SM, and
      female AO (7 replicates/group). Pigs in AO groups were all slaughtered after 6 wk
      on trial, whereas in SM groups the 3 heaviest pigs were removed and slaughtered 2
      wk before the remainder of the group, which were slaughtered at the same time as
      the AO pigs. Pigs were fed a liquid diet from a long trough 3 times daily.
      Behavioral observations were conducted before and after SM, the day of SM, and 1
      and 2 wk later. Behavior was recorded both during and between feed events, and
      skin lesions were scored on all, except the 3 pigs removed from SM groups before
      and 2 wk after SM. Growth performance, feed efficiency, and carcass traits were
      recorded. The number of aggressive interactions during feed events decreased
      after the 3 pigs were removed from SM groups. This reduction in aggressive
      interactions was observed on the day of SM in male groups (before SM: 24.3 vs.
      the day of SM: 14.7, SED = 3.31, P < 0.05 for interaction) and in subsequent
      observations in female groups (before SM: 21.4 vs. days after SM: 13.4, SED =
      3.31, P < 0.05 for interaction). However, SM had no effect on behaviors recorded
      between feed events or on the number and severity of skin lesions (P > 0.10).
      There were no differences between the 11 remaining pigs in SM groups and the 14
      pigs in AO groups in terms of growth performance, feed efficiency, and carcass
      traits of female or intact male pigs (P > 0.10). However, reduced within-pen CV
      in carcass weight was detected in pigs from SM groups compared with pigs from AO
      groups (8.6 vs. 10.9, SEM = 0.72, P < 0.05). Therefore, in restrictively fed
      pigs, a SM strategy improved the welfare of both female and intact male pigs by
      reducing aggressive interactions during feeding but had no effect on performance
      or carcass traits.

PMID- 21873542
TI  - Effect of injected and dietary iron in young pigs on blood hematology and
      postnatal pig growth performance.
AB  - The relationship of injected Fe doses on blood hematology and pig growth
      performance during both preweaning and postweaning periods was studied. In Exp.
      1, the effect of BW of 347 pigs injected with 200 mg of Fe (dextran)
      intramuscularly (i.m.) at birth on hemoglobin (Hb) and percent hematocrit (Hct)
      at weaning was assessed. As BW increased there was a decline (P < 0.01) in Hb and
      Hct. In Exp. 2, Fe injection doses and timing of injected Fe on blood hematology
      and pig growth were evaluated. Injections were as follows: 1) 200 mg of Fe at
      birth; 2) 300 mg of Fe at birth; or 3) 200 mg of Fe at birth + 100 mg of Fe at d
      10. A total of 269 pigs were allotted within litter to 3 treatments. The 2
      greater quantities of injected Fe (i.e., 300 or 200 + 100 mg of Fe) had similar
      but greater (P < 0.05) Hb and Hct values than pigs receiving 200 mg of Fe, but
      growth rates were similar at weaning. The effects of injecting 200 mg of Fe at
      birth and either saline or 100 mg of Fe at 10 d of age were investigated in Exp.
      3. Weaned pigs of each group were fed diets with 0, 80, or 160 mg/kg of added Fe
      for 35 d as a 2 * 3 factorial arrangement with 12 replicates (n = 360 pigs) in a
      randomized complete block design (RCB). The innate Fe contents of diets averaged
      200 mg/kg. The greater Fe injection group (200 + 100 mg) had greater (P < 0.01)
      Hb and Hct values through 14 d postweaning (P < 0.05) and greater (P < 0.01) Hct
      values through 21 d postweaning. As dietary Fe increased, Hb was greater only at
      d 14 (P < 0.05 4), whereas Hct increased linearly to d 35 (P < 0.01) postweaning.
      Dietary Fe resulted in linear increases (P < 0.01) in ADG from d 21 to 35 and d 0
      to 35. In Exp. 4, 3 dietary Fe (80, 160, and 240 mg/kg of diet), 2 injected Fe
      treatments (200 or 300 mg of Fe) at birth, and birth BW (<1.5 or >=1.5 kg) were
      evaluated as a 2 * 2 * 3 factorial arrangement of treatments in a RCB design with
      6 replicates (n = 280 pigs). The 300 mg of Fe injection group had lighter BW in
      both birth BW groups, with a birth BW * injected Fe interaction (P < 0.01). This
      resulted in the lighter birth BW pigs receiving 200 mg of Fe having greater BW
      gains to 240 mg/kg of dietary Fe, whereas light birth BW pigs injected with 300
      mg of Fe plateaued at 160 mg/kg of Fe. Pigs in the heavy birth BW group injected
      with 200 or 300 mg of Fe at birth responded similarly to dietary Fe postweaning.
      These results indicate that blood Hb and Hct were affected by pig BW at weaning,
      but the additional 100 mg of Fe i.m. at 10 d of age increased blood hematology
      and that Fe injected preweaning affected initial postweaning performance.

PMID- 21873543
TI  - Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly
      to classical Hodgkin lymphoma with ABVD may improve outcome.
AB  - The appropriate therapy for limited-stage nodular lymphocyte predominant Hodgkin
      lymphoma (NLPHL) is unclear. In contrast to classical Hodgkin lymphoma (CHL),
      chemotherapy is often omitted; however, it is unknown whether this impacts the
      risk of relapse. Herein, we compared the outcome of patients with limited-stage
      NLPHL treated in an era in which ABVD (doxorubicin, bleomycin, vinblastine, and
      dacarbazine) chemotherapy was routinely incorporated into the primary therapy to
      an earlier era in which radiotherapy (RT) was used as a single modality. Using
      the British Columbia Cancer Agency Lymphoid Cancer Database, 88 patients with
      limited-stage NLPHL (stage 1A/1B or 2A, nonbulky disease < 10 cm) were
      identified. Treatment followed era-specific guidelines: before 1993, (n = 32) RT
      alone; and 1993 to present (n = 56), ABVD-like chemotherapy for 2 cycles followed
      by RT with the exception of 14 patients who received ABVD chemotherapy alone.
      Most patients were male (75%) with stage I disease (61%). In an era-to-era
      comparison, the 10-year time to progression (98% vs 76% P = .0074), progression
      free survival (91% vs 65% P = .0024), and OS (93% vs 84%, P = .074) favored the
      ABVD treatment era compared with the RT alone era. Treating limited-stage NLPHL
      similarly to CHL may improve outcome compared with the use of radiation alone.

PMID- 21873544
TI  - Addition of rituximab to chemotherapy alone as first-line therapy improves
      overall survival in elderly patients with mantle cell lymphoma.
AB  - Clinical trials have demonstrated that rituximab improves overall survival in non
      Hodgkin lymphoma (NHL), except in mantle cell lymphoma (MCL). We used
      Surveillance Epidemiology and End Results (SEER)-Medicare data to compare
      survival in older MCL patients who began chemotherapy with or without rituximab
      within 180 days of diagnosis. Patients were followed from diagnosis (January 1999
      to December 2005) until death or the end of observation (December 2007). Medicare
      administrative and claims data were used to identify the date and cause of death
      and the immunochemotherapy regimen. Of 638 patients, the mean age at diagnosis
      was 75 years, 75% had stage III/IV disease, 67% had extranodal involvement, and
      64% received rituximab. The average length of first-line treatment was 21 weeks,
      with no difference between the 2 groups (P = .76). Median survival was 27 months
      for chemotherapy alone, compared with 37 months for chemotherapy plus rituximab
      (P < .001). In multivariate analysis of 2-year survival, rituximab plus
      chemotherapy was associated with lower all-cause (hazard ratio [HR] 0.58; 95%
      confidence interval [CI] 0.41-0.82; P < .01), and cancer-specific (HR 0.56; 95%
      CI 0.37-0.84; P < .01) mortality. Results were similar when using the entire
      observation period, propensity score analysis, and limiting chemotherapy to
      CHOP/CHOP-like. We conclude that first-line chemotherapy including rituximab is
      associated with significantly improved survival in older patients diagnosed with
      MCL.

PMID- 21873545
TI  - Coordinate loss of a microRNA and protein-coding gene cooperate in the
      pathogenesis of 5q- syndrome.
AB  - Large chromosomal deletions are among the most common molecular abnormalities in
      cancer, yet the identification of relevant genes has proven difficult. The 5q-
      syndrome, a subtype of myelodysplastic syndrome (MDS), is a chromosomal deletion
      syndrome characterized by anemia and thrombocytosis. Although we have previously
      shown that hemizygous loss of RPS14 recapitulates the failed erythroid
      differentiation seen in 5q- syndrome, it does not affect thrombocytosis. Here we
      show that a microRNA located in the common deletion region of 5q- syndrome, miR
      145, affects megakaryocyte and erythroid differentiation. We find that miR-145
      functions through repression of Fli-1, a megakaryocyte and erythroid regulatory
      transcription factor. Patients with del(5q) MDS have decreased expression of miR
      145 and increased expression of Fli-1. Overexpression of miR-145 or inhibition of
      Fli-1 decreases the production of megakaryocytic cells relative to erythroid
      cells, whereas inhibition of miR-145 or overexpression of Fli-1 has a reciprocal
      effect. Moreover, combined loss of miR-145 and RPS14 cooperates to alter
      erythroid-megakaryocytic differentiation in a manner similar to the 5q- syndrome.
      Taken together, these findings demonstrate that coordinate deletion of a miRNA
      and a protein-coding gene contributes to the phenotype of a human malignancy, the
      5q- syndrome.

PMID- 21873546
TI  - Hepcidin regulation by innate immune and infectious stimuli.
AB  - Hepcidin controls the levels and distribution of iron, an element whose
      availability can influence the outcome of infections. We investigated hepcidin
      regulation by infection-associated cytokines, pathogen-derived molecules, and
      whole pathogens in vitro and in vivo. We found that IL-22, an effector cytokine
      implicated in responses to extracellular infections, caused IL-6-independent
      hepcidin up-regulation in human hepatoma cells, suggesting it might represent an
      additional inflammatory hepcidin agonist. Like IL-6, IL-22 caused phosphorylation
      of STAT3 and synergized with BMP6 potentiating hepcidin induction. In human
      leukocytes, IL-6 caused potent, transient hepcidin up-regulation that was
      augmented by TGF-beta1. Pathogen-derived TLR agonists also stimulated hepcidin,
      most notably the TLR5 agonist flagellin in an IL-6-dependent manner. In contrast,
      leukocyte hepcidin induction by heat-killed Candida albicans hyphae was IL-6
      independent, but partially TGF-beta-dependent. In a murine acute systemic
      candidiasis model, C albicans strongly stimulated hepcidin, accompanied by a
      major reduction in transferrin saturation. Similarly, hepcidin was up-regulated
      with concomitant lowering of serum iron during acute murine Influenza A/PR/8/34
      virus (H1N1) infection. This intracellular pathogen also stimulated hepcidin
      expression in leukocytes and hepatoma cells. Together, these results indicate
      that hepcidin induction represents a component of the innate immune response to
      acute infection, with the potential to affect disease pathogenesis.

PMID- 21873547
TI  - TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin
      levels in normal individuals.
AB  - The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine
      protease encoded by the TMPRSS6 gene. Cleaving the bone morphogenetic protein
      (BMP) coreceptor hemojuvelin (HJV), MT2 impairs the BMP/son of mothers against
      decapentaplegic homologs (SMAD) signaling pathway, down-regulates hepcidin, and
      facilitates iron absorption. TMPRSS6 inactivation causes iron-deficiency anemia
      refractory to iron administration both in humans and mice. Genome-wide
      association studies have shown that the SNP rs855791, which causes the MT2 V736A
      amino acid substitution, is associated with variations of serum iron, transferrin
      saturation, hemoglobin, and erythrocyte traits. In the present study, we show
      that, in vitro, MT2 736(A) inhibits hepcidin more efficiently than 736(V).
      Moreover, in a genotyped population, after exclusion of samples with iron
      deficiency and inflammation, hepcidin, hepcidin/transferrin saturation, and
      hepcidin/ferritin ratios were significantly lower and iron parameters were
      consistently higher in homozygotes 736(A) than in 736(V). Our results indicate
      that rs855791 is a TMPRSS6 functional variant and strengthen the idea that even a
      partial inability to modulate hepcidin influences iron parameters and,
      indirectly, erythropoiesis.

PMID- 21873548
TI  - Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and
      adult AML: a report from the Children's Oncology Group and SWOG.
AB  - IDH1 SNP rs11554137 was recently reported in association with poor prognosis in
      normal karyotype adult acute myeloid leukemia (AML). We aimed to determine the
      prevalence, clinical associations, and prognostic significance of SNP rs11554137
      in unselected pediatric and adult AML patients. Diagnostic marrow specimens from
      527 AML patients treated on the pediatric trial Children's Oncology Group
      AAML03P1 (N = 253) or adult SWOG trials (N = 274) were analyzed for the presence
      of the SNP. SNP rs11554137 was present in 11% of all patients. SNP status had no
      prognostic impact on survival in pediatric patients. In adult AML, overall
      survival for SNP-positive patients was 10% versus 18% for SNP-negative patients
      (P = .44). Among the 142 adults who achieved complete remission, 5-year relapse
      free survival was significantly worse for SNP-positive patients (0% vs 25%, P =
      .0014). However, among adults with normal cytogenetics, FLT3/ITD was present in
      90% of SNP-positive patients versus 59% of SNP-negative patients (P = .0053). In
      multivariate analysis, adjusting for the effects of age, cytogenetics, and
      FLT3/ITD, the independent prognostic effect of SNP positivity was not
      statistically significant (hazard ratio = 1.72, P = .18). The clinical profile of
      SNP-positive patients suggests that SNP rs11554137 may have biologic effects that
      bear further investigation. The clinical trials in this study are registered at
      http://www.clinicaltrials.gov as #NCT000707174 and #NCT00899171.

PMID- 21873550
TI  - Obesity-associated hepatosteatosis and impairment of glucose homeostasis are
      attenuated by haptoglobin deficiency.
AB  - OBJECTIVE: Haptoglobin (Hp) is upregulated in both inflammation and obesity. The
      low chronic inflammatory state, caused by massive adipose tissue macrophage (ATM)
      infiltration found in obesity, and low adiponectin have been implicated in the
      development of insulin resistance and hepatosteatosis. The aim of this work was
      to investigate whether and how Hp interferes with the onset of obesity-associated
      complications. RESEARCH DESIGN AND METHODS: Hp-null (Hp(-/-)) and wild-type (WT)
      mice were metabolically profiled under chow-food diet (CFD) and high-fat diet
      (HFD) feeding by assessing physical parameters, glucose tolerance, insulin
      sensitivity, insulin response to glucose load, liver triglyceride content, plasma
      levels of leptin, insulin, glucose, and adiponectin. ATM content was evaluated by
      using immunohistochemistry (anti-F4/80 antibody). Adiponectin expression was
      measured in Hp-treated, cultured 3T3-L1 and human adipocytes. RESULTS: No
      genotype-related difference was found in CFD animals. HFD-Hp(-/-) mice revealed
      significantly higher glucose tolerance, insulin sensitivity, glucose-stimulated
      insulin secretion, and adiponectin expression and reduced hepatomegaly/steatosis
      compared with HFD-WT mice. White adipose tissue (WAT) of HFD-Hp(-/-) mice showed
      higher activation of insulin signaling cascade, lower ATM, and higher adiponectin
      expression. Hp was able to inhibit adiponectin expression in cultured adipocytes.
      CONCLUSIONS: We demonstrated that in the absence of Hp, obesity-associated
      insulin resistance and hepatosteatosis are attenuated, which is associated with
      reduced ATM content, increased plasma adiponectin, and higher WAT insulin
      sensitivity.

PMID- 21873551
TI  - Donor islet endothelial cells in pancreatic islet revascularization.
AB  - OBJECTIVE: Freshly isolated pancreatic islets contain, in contrast to cultured
      islets, intraislet endothelial cells (ECs), which can contribute to the formation
      of functional blood vessels after transplantation. We have characterized how
      donor islet endothelial cells (DIECs) may contribute to the revascularization
      rate, vascular density, and endocrine graft function after transplantation of
      freshly isolated and cultured islets. RESEARCH DESIGN AND METHODS: Freshly
      isolated and cultured islets were transplanted under the kidney capsule and into
      the anterior chamber of the eye. Intravital laser scanning microscopy was used to
      monitor the revascularization process and DIECs in intact grafts. The grafts'
      metabolic function was examined by reversal of diabetes, and the ultrastructural
      morphology by transmission electron microscopy. RESULTS: DIECs significantly
      contributed to the vasculature of fresh islet grafts, assessed up to 5 months
      after transplantation, but were hardly detected in cultured islet grafts. Early
      participation of DIECs in the revascularization process correlated with a higher
      revascularization rate of freshly isolated islets compared with cultured islets.
      However, after complete revascularization, the vascular density was similar in
      the two groups, and host ECs gained morphological features resembling the
      endogenous islet vasculature. Surprisingly, grafts originating from cultured
      islets reversed diabetes more rapidly than those originating from fresh islets.
      CONCLUSIONS: In summary, DIECs contributed to the revascularization of fresh, but
      not cultured, islets by participating in early processes of vessel formation and
      persisting in the vasculature over long periods of time. However, the DIECs did
      not increase the vascular density or improve the endocrine function of the
      grafts.

PMID- 21873552
TI  - Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin
      resistance: another paradox in endurance-trained athletes?
AB  - OBJECTIVE: Chronic exercise and obesity both increase intramyocellular
      triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We
      hypothesized that chronically exercise-trained muscle would be characterized by
      lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs
      and would account for its higher insulin sensitivity. We also hypothesized that
      the expression of key skeletal muscle proteins involved in lipid droplet
      hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be
      associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS: A total of
      14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight
      sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied.
      Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and
      protein expression were measured in muscle biopsies. RESULTS: DAG content in the
      NWA group was approximately twofold higher than in the OBS group and ~50% higher
      than in the NWS group, corresponding to higher insulin sensitivity. While certain
      DAG moieties clearly were associated with better insulin sensitivity, other
      species were not. Ceramide content was higher in insulin-resistant obese muscle.
      The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl
      CoA desaturase protein was higher in the NWA group, corresponding to a higher
      mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin
      sensitivity. CONCLUSIONS: Total myocellular DAGs were markedly higher in highly
      trained athletes, corresponding with higher insulin sensitivity, and suggest a
      more complex role for DAGs in insulin action. Our data also provide additional
      evidence in humans linking ceramides to insulin resistance. Finally, this study
      provides novel evidence supporting a role for specific skeletal muscle proteins
      involved in intramyocellular lipids, mitochondrial oxidative capacity, and
      insulin resistance.

PMID- 21873553
TI  - Genetic analysis of adult-onset autoimmune diabetes.
AB  - OBJECTIVE: In contrast with childhood-onset type 1 diabetes, the genetics of
      autoimmune diabetes in adults are not well understood. We have therefore
      investigated the genetics of diabetes diagnosed in adults positive for
      autoantibodies. RESEARCH DESIGN AND METHODS: GAD autoantibodies (GADAs),
      insulinoma-associated antigen-2 antibodies (IA-2As), and islet cell
      autoantibodies were measured at time of diagnosis. Autoantibody-positive diabetic
      subjects (n = 1,384) and population-based control subjects (n = 2,235) were
      genotyped at 20 childhood-onset type 1 diabetes loci and FCRL3, GAD2, TCF7L2, and
      FTO. RESULTS: PTPN22 (1p13.2), STAT4 (2q32.2), CTLA4 (2q33.2), HLA (6p21), IL2RA
      (10p15.1), INS (11p15.5), ERBB3 (12q13.2), SH2B3 (12q24.12), and CLEC16A
      (16p13.13) were convincingly associated with autoimmune diabetes in adults (P <=
      0.002), with consistent directions of effect as reported for pediatric type 1
      diabetes. No evidence of an HLA-DRB1*03/HLA-DRB1*04 (DR3/4) genotype effect was
      obtained (P = 0.55), but it remained highly predisposing (odds ratio 26.22).
      DR3/4 was associated with a lower age at diagnosis of disease, as was DR4 (P =
      4.67 * 10(-6)) but not DR3. DR3 was associated with GADA positivity (P = 6.03 *
      10(-6)) but absence of IA-2A (P = 3.22 * 10(-7)). DR4 was associated with IA-2A
      positivity (P = 5.45 * 10(-6)). CONCLUSIONS: Our results are consistent with the
      hypothesis that the genetics of autoimmune diabetes in adults and children are
      differentiated by only relatively few age-dependent genetic effects. The slower
      progression toward autoimmune insulin deficiency in adults is probably due to a
      lower genetic load overall combined with subtle variation in the HLA class II
      gene associations and autoreactivity.

PMID- 21873554
TI  - Disruption of hypoxia-inducible factor 1 in adipocytes improves insulin
      sensitivity and decreases adiposity in high-fat diet-fed mice.
AB  - OBJECTIVE: Obesity, insulin resistance, and type 2 diabetes form a tightly
      correlated cluster of metabolic disorders in which adipose is one of the first
      affected tissues. The role of hypoxia and hypoxia-inducible factor 1 (HIF1) in
      the development of high-fat diet (HFD)-induced obesity and insulin resistance was
      investigated using animal models. RESEARCH DESIGN AND METHODS: Mice with
      adipocyte-specific targeted disruption of the genes encoding the HIF1 obligatory
      subunits Hif1alpha or Arnt (Hif1beta) were generated using an aP2-Cre transgene
      with the Cre/LoxP system. The mice were fed an HFD for 12 weeks and their
      metabolic phenotypes were determined. Gene expression patterns in adipose tissues
      were also determined by microarray and quantitative PCR. RESULTS: On an HFD,
      adipocyte-specific ARNT knockout mice and adipocyte-specific HIF1alpha knockout
      mice exhibit similar metabolic phenotypes, including reduced fat formation,
      protection from HFD-induced obesity, and insulin resistance compared with
      similarly fed wild-type controls. The cumulative food intake remained similar;
      however, the metabolic efficiency was lower in adipocyte-specific HIF1alpha
      knockout mice. Moreover, indirect calorimetry revealed respiratory exchange
      ratios were reduced in adipocyte-specific HIF1alpha knockout mice.
      Hyperinsulinemic-euglycemic clamp studies demonstrated that targeted disruption
      of HIF1alpha in adipocytes enhanced whole-body insulin sensitivity. The
      improvement of insulin resistance is associated with decreased expression of
      Socs3 and induction of adiponectin. CONCLUSIONS: Inhibition of HIF1 in adipose
      tissue ameliorates obesity and insulin resistance. This study reveals that HIF1
      could provide a novel potential therapeutic target for obesity and type 2
      diabetes.

PMID- 21873555
TI  - Kupffer cell depletion prevents but has no therapeutic effect on metabolic and
      inflammatory changes induced by a high-fat diet.
AB  - We aimed to evaluate activation of macrophages in insulin-sensitive tissues
      (liver, adipose tissue, and muscles) under high-fat diet (HFD) and elucidate the
      role of Kupffer cells (KC) in HFD-induced insulin resistance. Tissue macrophage
      populations, insulin signaling, and sensitivity were evaluated in mice fed a HFD
      for 4 or 16 wk. Selective KC depletion was obtained by intravenous injections of
      liposome-encapsulated clodronate. Mice fed a HFD for 4 to 16 wk have hepatic and
      peripheral insulin resistance together with macrophage recruitment in the adipose
      tissue but not in the liver. Depletion of KC for the last 10 d of the 16 wk
      experiment fails to improve insulin sensitivity compared to PBS-treated animals.
      In contrast, preventive KC depletion prior to and during the 4 wk HFD attenuates
      the development of obesity, adiposity, adipose tissue inflammation (P<0.01 vs.
      PBS group), and insulin resistance (P<0.01). Interestingly, in mice fed a normal
      diet, prolonged KC depletion ameliorates insulin sensitivity and decreases
      adiposity without altering physiological body weight gain or food intake.
      Preventive and prolonged KC depletion ameliorates insulin sensitivity and
      prevents adipose tissue inflammation, suggesting a communication between the
      liver and the adipose tissue in the development of HFD-induced metabolic
      alterations.

PMID- 21873557
TI  - Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with
      improved bacterial clearance.
AB  - Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of
      septic mice. However, the molecular mechanisms underlying the cholesterol
      lowering, independent beneficial effects of statins in sepsis are poorly
      understood. The inhibition of protein isoprenylation, namely farnesylation and
      geranylgeranylation, has been proposed as a mediator of the pleiotropic
      protective effects of statins, although direct evidence is lacking. Major
      features of sepsis-induced immune suppression include T-cell dysfunction, which
      is characterized by apoptosis of splenic T cells, increased CD4(+)Foxp3(+)
      regulatory T cells (Tregs), and suppression of type 1 helper T-cell response
      [e.g., interferon-gamma (IFN-gamma) secretion] in mice. Here, we show that the
      induction of sepsis by cecal ligation and puncture (CLP) resulted in increases in
      farnesyltransferase activity and farnesylated proteins in the spleen relative to
      sham operation. Treatment with farnesyltransferase inhibitor N-[4-[2(R)-amino-3
      mercaptopropyl]amino-2-phenylbenzoyl]methionine methyl ester trifluoroacetate
      salt (FTI-277) (25 mg/kg b.wt. i.p.) at 2 h after CLP blocked the increase in
      farnesylated proteins and improved survival and bacterial clearance of septic
      mice. FTI-277 reverted to or mitigated sepsis-induced apoptosis in spleen and
      thymus, increased splenic CD4(+)Foxp3(+) Tregs, and suppressed IFN-gamma
      secretion and proliferation of splenocytes in response to anti-CD3+CD28
      antibodies in mice. Moreover, FTI-277 promoted macrophage phagocytotic activity
      in septic mice. These results indicate that elevation in protein farnesylation
      plays a role in derangements in immune function and mortality of septic mice.
      These findings suggest that prevention of immune dysfunction might contribute to
      FTI-277-induced improvement in survival of septic mice. These data highlight
      protein farnesyltransferase as a novel potential molecular target to reduce the
      mortality of patients with sepsis.

PMID- 21873558
TI  - Effect of serum 25-hydroxyvitamin D on risk for type 2 diabetes may be partially
      mediated by subclinical inflammation: results from the MONICA/KORA Augsburg
      study.
AB  - OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D (25-OHD)
      and incident type 2 diabetes and to determine whether the association is mediated
      by subclinical inflammation. RESEARCH DESIGN AND METHODS: Using a case-cohort
      design, baseline levels of 25-OHD were measured in 416 case subjects with
      incident type 2 diabetes and 1,267 noncase subjects selected from a source
      population of 7,936 middle-aged participants in the population-based Monitoring
      of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health
      Research in the Region of Augsburg (KORA) study. RESULTS: A significant inverse
      association was observed between serum 25-OHD and incident type 2 diabetes after
      adjustment for diabetes risk factors and season. The hazard ratio (HR) and 95% CI
      comparing tertile extremes was 0.63 (0.44-0.90) (P(trend) = 0.010). Further
      adjustment for C-reactive protein, interleukin-6, soluble intercellular adhesion
      molecule-1, and interferon-gamma-inducible protein-10 attenuated this association
      by 16% (HR 0.73 [0.50-1.05], P = 0.090). CONCLUSIONS: Vitamin D status is
      inversely related to type 2 diabetes risk and our data suggest that this
      association may be partially mediated by subclinical inflammation.

PMID- 21873556
TI  - Enhanced Ca2+ entry due to Orai1 plasma membrane insertion increases IL-8
      secretion by cystic fibrosis airways.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF
      transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508,
      causes retention of CFTR in the endoplasmic reticulum (ER). Some CF abnormalities
      can be explained by altered Ca(2+) homeostasis, although it remains unknown how
      CFTR influences calcium signaling. This study examined the novel hypothesis that
      store-operated calcium entry (SOCE) through Orai1 is abnormal in CF. The
      significance of Orai1-mediated SOCE for increased interleukin-8 (IL-8) expression
      in CF was also investigated. CF and non-CF human airway epithelial cell line and
      primary cells (obtained at lung transplantation) were used in Ca(2+) imaging,
      electrophysiology, and fluorescence imaging experiments to explore differences in
      Orai1 function in CF vs. non-CF cells. Protein expression and localization was
      assessed by Western blots, cell surface biotinylation, ELISA, and image
      correlation spectroscopy (ICS). We show here that store-operated Ca(2+) entry
      (SOCE) is elevated in CF human airway epithelial cells (hAECs; ~ 1.8- and ~ 2.5
      fold for total Ca(2+)(i) increase and Ca(2+) influx rate, respectively, and ~ 2
      fold increase in the I(CRAC) current) and is caused by increased exocytotic
      insertion (~ 2-fold) of Orai1 channels into the plasma membrane, which is
      normalized by rescue of DeltaF508-CFTR trafficking to the cell surface. Augmented
      SOCE in CF cells is a major factor leading to increased IL-8 secretion (~ 2
      fold). CFTR normally down-regulates the Orai1/stromal interaction molecule 1
      (STIM1) complex, and loss of this inhibition due to the absence of CFTR at the
      plasma membrane helps to explain the potentiated inflammatory response in CF
      cells.

PMID- 21873559
TI  - Self-reported long total sleep duration is associated with metabolic syndrome:
      the Guangzhou Biobank Cohort Study.
AB  - OBJECTIVE: To examine the association between total sleep duration and the
      prevalence of metabolic syndrome (MetSyn) in older Chinese. RESEARCH DESIGN AND
      METHODS: Cross-sectional analysis of baseline data from the Guangzhou Biobank
      Cohort Study (GBCS) was performed. Participants (n = 29,333) were aged >=50
      years. Risk of MetSyn and its components were identified for self-reported total
      sleep duration. RESULTS: Participants reporting long (>=9 h) and short (<6 h)
      total sleep duration had increased odds ratio (OR) of 1.18 (95% CI 1.07-1.30) and
      1.14 (1.05-1.24) for the presence of MetSyn, respectively. The relationship
      remained in long sleepers (OR 1.21 [1.10-1.34]) but diminished in short sleepers
      (0.97 [0.88-1.06]) after full adjustment. CONCLUSIONS: Long sleep duration was
      associated with greater risk of MetSyn in older Chinese. Confirmation through
      longitudinal studies is needed. The mechanisms mediating the link between long
      sleep duration and MetSyn require further investigation.

PMID- 21873560
TI  - Effects of a home-based walking intervention on mobility and quality of life in
      people with diabetes and peripheral arterial disease: a randomized controlled
      trial.
AB  - OBJECTIVE: Determine the efficacy of a home-based walking intervention to improve
      walking ability and quality of life in people with diabetes and peripheral
      arterial disease (PAD). RESEARCH DESIGN AND METHODS: We conducted a randomized,
      controlled, single-blind trial within university-affiliated clinics in our local
      community. We randomized 145 participants (45 women) with diabetes and PAD to our
      intervention--a 6-month behavioral intervention targeting levels of readiness to
      engage in routine walking for exercise--versus attention control. Our primary
      outcome was 6-month change in maximal treadmill walking distance. Secondary
      outcomes included 3-month change in maximal walking distance, lower limb function
      (i.e., walking impairment scores), quality of life (Medical Outcomes Short Form
      Survey), exercise behaviors, depressive symptoms, and self-efficacy at 3 and 6
      months. RESULTS: The mean age of participants was 66.5 (SD 10.1) years.
      Intervention and control groups did not differ significantly in 6-month change in
      maximal treadmill walking distance (average [SE] 24.5 [19.6] meters vs. 39.2
      [19.6] meters; P = 0.60). Among secondary outcomes, for the intervention and
      control groups, respectively, average walking speed scores increased by 5.7 [2.2]
      units and decreased by 1.9 [2.8] units (P = 0.03); the mental health quality of
      life subscale score increased by 3.2 [1.5] and decreased by 2.4 [1.5] units (P =
      0.01). CONCLUSIONS: A home-based walking intervention did not improve walking
      distance but did improve walking speed and quality of life in people with
      diabetes and PAD. Clinicians should consider recommending home-based walking
      therapy for such patients.

PMID- 21873561
TI  - Telomere dysfunction-related serological markers are associated with type 2
      diabetes.
AB  - OBJECTIVE: Recent studies have identified a set of serological markers for
      telomere dysfunction and DNA damage. The relevance of these serological markers
      in type 2 diabetes remains elusive. We investigated the association of
      serological markers (elongation factor 1alpha [EF-1alpha], stathmin, and N-acetyl
      glucosaminidase) with leukocyte telomere length, a functional variant of
      uncoupling protein-2 (UCP2), and susceptibility of type 2 diabetes. RESEARCH
      DESIGN AND METHODS: A total of 930 patients and 867 control subjects were
      recruited to examine the association between leukocyte telomere length, UCP2
      variant (-886G>A), recently identified serological markers, and type 2 diabetes.
      Telomere length was determined by a quantitative real-time PCR-based assay. EF
      1alpha, stathmin, and C-reactive proteins were measured by enzyme-linked
      immunosorbent assays. N-acetyl-glucosaminidase was measured by an enzyme activity
      assay. The UCP2 variant was determined by PCR and restriction enzyme digestion.
      RESULTS: The average telomere length of type 2 diabetic patients was
      significantly shorter than that of control subjects. Serological N-acetyl
      glucosaminidase correlates with both age and telomere length and was
      significantly higher in patients than in control subjects. Neither EF-1alpha nor
      stathmin showed significant difference between patients and control subjects. The
      UCP2-886G>A variant correlated with type 2 diabetes status but did not correlate
      with telomere length or the serological markers. Multivariate analysis showed
      that higher serological N-acetyl-glucosaminidase, shorter telomeres, and the UCP2
      886G>A variant are independent risk factors for type 2 diabetes. CONCLUSIONS:
      Serological N-acetyl-glucosaminidase, telomere length, and the UCP2-886G>A
      variant are independent risk factors for type 2 diabetes. Serological N-acetyl
      glucosaminidase correlates with telomere length but not with the UCP2-886G>A
      variant.

PMID- 21873562
TI  - Elevated transferrin saturation and risk of diabetes: three population-based
      studies.
AB  - OBJECTIVE: We tested the hypothesis that elevated transferrin saturation is
      associated with an increased risk of any form of diabetes, as well as type 1 or
      type 2 diabetes separately. RESEARCH DESIGN AND METHODS: We used two general
      population studies, The Copenhagen City Heart Study (CCHS, N = 9,121) and The
      Copenhagen General Population Study (CGPS, N = 24,195), as well as a 1:1 age- and
      sex-matched population-based case-control study with 6,129 patients with diabetes
      from the Steno Diabetes Centre and 6,129 control subjects, totaling 8,535
      patients with diabetes and 37,039 control subjects. RESULTS: In the combined
      studies, odds ratios in those with transferrin saturation >=50% vs. <50% were 2.1
      (95% CI 1.3-3.4; P = 0.003) for any form of diabetes; 2.6 (1.2-5.6; P = 0.01) for
      type 1 diabetes; and 1.7 (1.4-2.1; P = 0.001) for type 2 diabetes. CONCLUSIONS:
      Elevated transferrin saturation confers a two- to threefold increased risk of
      developing any form of diabetes, as well as type 1 and type 2 diabetes
      separately.

PMID- 21873563
TI  - Metabolic syndrome does not detect metabolic risk in African men living in the
      U.S.
AB  - OBJECTIVE: Metabolic risk and metabolic syndrome (MetSyn) prevalence were
      compared in Africans who immigrated to the U.S. and African Americans. If MetSyn
      were an effective predictor of cardiometabolic risk, then the group with a worse
      metabolic risk profile would have a higher rate of MetSyn. RESEARCH DESIGN AND
      METHODS: Cross-sectional analyses were performed on 95 men (39 Africans, 56
      African Americans, age 38 +/- 6 years [mean +/- SD]). Glucose tolerance was
      determined by oral glucose tolerance test, visceral adipose tissue (VAT) was
      determined by computerized tomography, and MetSyn was determined by the presence
      of three of five factors: central obesity, hypertriglyceridemia, low levels of
      HDL cholesterol, hypertension, and fasting hyperglycemia. RESULTS: MetSyn
      prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74),
      but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in
      Africans. CONCLUSIONS: African immigrants have a worse metabolic profile than
      African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may
      underpredict metabolic risk in Africans.

PMID- 21873549
TI  - Genome-wide association identifies nine common variants associated with fasting
      proinsulin levels and provides new insights into the pathophysiology of type 2
      diabetes.
AB  - OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher
      circulating proinsulin levels are associated with impaired beta-cell function,
      raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of
      the insulin processing pathway could provide new insights about T2D
      pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis
      of genome-wide association tests of ~2.5 million genotyped or imputed single
      nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701
      nondiabetic adults of European ancestry, with follow-up of 23 loci in up to
      16,378 individuals, using additive genetic models adjusted for age, sex, fasting
      insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were
      associated with proinsulin levels (P < 5 * 10(-8)). Two loci (LARP6 and SGSM2)
      have not been previously related to metabolic traits, one (MADD) has been
      associated with fasting glucose, one (PCSK1) has been implicated in obesity, and
      four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D
      risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting
      glucose (P = 1.7 * 10(-4)), improved beta-cell function (P = 1.1 * 10(-5)), and
      lower risk of T2D (odds ratio 0.88; P = 7.8 * 10(-6)). Notably, PCSK1 encodes the
      protein prohormone convertase 1/3, the first enzyme in the insulin processing
      pathway. A genotype score composed of the nine proinsulin-raising alleles was not
      associated with coronary disease in two large case-control datasets. CONCLUSIONS:
      We have identified nine genetic variants associated with fasting proinsulin. Our
      findings illuminate the biology underlying glucose homeostasis and T2D
      development in humans and argue against a direct role of proinsulin in coronary
      artery disease pathogenesis.

PMID- 21873564
TI  - Cardiac geometry and function in diabetic or prediabetic adolescents and young
      adults: the Strong Heart Study.
AB  - OBJECTIVE: The aim of this study was to evaluate whether diabetes (DM) and
      impaired fasting glucose (IFG) were associated with early alterations in left
      ventricular geometry and function in a large population of adolescents and young
      adults independently of major confounders. RESEARCH DESIGN AND METHODS: We
      analyzed echocardiographic data of 1,624 14- to 39-year-old participants (mean
      age 26.6 +/- 7.7 years; 57% female) without prevalent cardiovascular disease from
      the fourth Strong Heart Study examination; 179 (11%) participants had DM and 299
      (18%) had IFG. RESULTS: Participants with DM and IFG were older and more often
      obese and hypertensive than participants with normal fasting glucose (NFG) (all P
      < 0.05). After adjustment for age, sex, systolic blood pressure, and body fat,
      diabetic and IFG participants had higher left ventricular mass index than those
      with NFG (41.5 +/- 8.7 and 39.6 +/- 9.2 vs. 35.6 +/- 7.8 g/m(2.7)) and reduced
      stress-corrected midwall shortening (98 +/- 8.6 and 99 +/- 7.5 vs. 101 +/- 8.5%;
      all P < 0.05). The prevalence of left ventricular hypertrophy was higher in DM
      (20%) and IFG (17%) than in NFG participants (12%; P < 0.05). Compared with the
      other groups, DM was also associated with higher prevalence of inappropriate left
      ventricular mass, concentric geometry, and more diastolic abnormalities
      independently of covariates (all P < 0.05). CONCLUSIONS: In a population of
      adolescents and young adults, DM is independently associated with early
      unfavorable cardiovascular phenotype characterized by increased left ventricular
      mass, concentric geometry, and early preclinical systolic and diastolic
      dysfunction; early cardiovascular alterations are also present in participants
      with prediabetes.

PMID- 21873566
TI  - MAP65-3 cross-links interdigitated microtubules in the phragmoplast.

PMID- 21873565
TI  - Interaction of antiparallel microtubules in the phragmoplast is mediated by the
      microtubule-associated protein MAP65-3 in Arabidopsis.
AB  - In plant cells, microtubules (MTs) in the cytokinetic apparatus phragmoplast
      exhibit an antiparallel array and transport Golgi-derived vesicles toward MT plus
      ends located at or near the division site. By transmission electron microscopy,
      we observed that certain antiparallel phragmoplast MTs overlapped and were
      bridged by electron-dense materials in Arabidopsis thaliana. Robust MT
      polymerization, reported by fluorescently tagged End Binding1c (EB1c), took place
      in the phragmoplast midline. The engagement of antiparallel MTs in the central
      spindle and phragmoplast was largely abolished in mutant cells lacking the MT
      associated protein, MAP65-3. We found that endogenous MAP65-3 was selectively
      detected on the middle segments of the central spindle MTs at late anaphase. When
      MTs exhibited a bipolar appearance with their plus ends placed in the middle,
      MAP65-3 exclusively decorated the phragmoplast midline. A bacterially expressed
      MAP65-3 protein was able to establish the interdigitation of MTs in vitro. MAP65
      3 interacted with antiparallel microtubules before motor Kinesin-12 did during
      the establishment of the phragmoplast MT array. Thus, MAP65-3 selectively cross
      linked interdigitating MTs (IMTs) to allow antiparallel MTs to be closely engaged
      in the phragmoplast. Although the presence of IMTs was not essential for vesicle
      trafficking, they were required for the phragmoplast-specific motors Kinesin-12
      and Phragmoplast-Associated Kinesin-Related Protein2 to interact with MT plus
      ends. In conclusion, we suggest that the phragmoplast contains IMTs and highly
      dynamic noninterdigitating MTs, which work in concert to bring about cytokinesis
      in plant cells.

PMID- 21873568
TI  - Gender-bias primes elicit queen-bee responses among senior policewomen.
AB  - Queen bees are senior women in male-dominated organizations who have achieved
      success by emphasizing how they differ from other women. Although the behavior of
      queen bees tends to be seen as contributing to gender disparities in career
      outcomes, we argue that queen-bee behavior is actually a result of the gender
      bias and social identity threat that produce gender disparities in career
      outcomes. In the experiment reported here, we asked separate groups of senior
      policewomen to recall the presence or absence of gender bias during their
      careers, and we measured queen-bee responses (i.e., masculine self-descriptions,
      in-group distancing, and denying of discrimination). Such gender-bias priming
      increased queen-bee responses among policewomen with low gender identification,
      but policewomen with high gender identification responded with increased
      motivation to improve opportunities for other women. These results suggest that
      gender-biased work environments shape women's behavior by stimulating women with
      low gender identification to dissociate with other women and to display queen-bee
      responses as a way to achieve individual mobility.

PMID- 21873567
TI  - Quantitative proteomic analysis of cellular protein modulation upon inhibition of
      the NEDD8-activating enzyme by MLN4924.
AB  - Cullin-RING ubiquitin ligases (CRLs) are responsible for the ubiquitination of
      many cellular proteins, thereby targeting them for proteasomal degradation. In
      most cases the substrates of the CRLs have not been identified, although many of
      those that are known have cancer relevance. MLN4924, an investigational small
      molecule that is a potent and selective inhibitor of the Nedd8-activating enzyme
      (NAE), is currently being explored in Phase I clinical trials. Inhibition of
      Nedd8-activating enzyme by MLN4924 prevents the conjugation of cullin proteins
      with NEDD8, resulting in inactivation of the entire family of CRLs. We have
      performed stable isotope labeling with amino acids in cell culture analysis of
      A375 melanoma cells treated with MLN4924 to identify new CRL substrates,
      confidently identifying and quantitating 5122-6012 proteins per time point.
      Proteins such as MLX, EID1, KLF5, ORC6L, MAGEA6, MORF4L2, MRFAP1, MORF4L1, and
      TAX1BP1 are rapidly stabilized by MLN4924, suggesting that they are novel CRL
      substrates. Proteins up-regulated at later times were also identified and siRNA
      against their corresponding genes were used to evaluate their influence on
      MLN4924-induced cell death. Thirty-eight proteins were identified as being
      particularly important for the cytotoxicity of MLN4924. Strikingly, these
      proteins had roles in cell cycle, DNA damage repair, and ubiquitin transfer.
      Therefore, the combination of RNAi with stable isotope labeling with amino acids
      in cell culture provides a paradigm for understanding the mechanism of action of
      novel agents affecting the ubiquitin proteasome system and a path to identifying
      mechanistic biomarkers.

PMID- 21873569
TI  - Structural priming across cognitive domains: from simple arithmetic to relative
      clause attachment.
AB  - In the two experiments reported here, we uncovered evidence for shared structural
      representations between arithmetic and language. Specifically, we primed subjects
      using mathematical equations either with or without parenthetical groupings, such
      as 80 - (9 + 1) * 5 or 80 - 9 + 1 * 5, and then presented a target sentence
      fragment, such as "The tourist guide mentioned the bells of the church that . .
      .," which subjects had to complete. When the mathematical equations were solved
      correctly, their structure influenced the noun phrase--for example, either "the
      bells of the church" or "the church," respectively--that subjects chose to attach
      their sentence completion to. These experiments provide the first demonstration
      of cross-domain structural priming from mathematics to language. They highlight
      the importance of global structural representations at a very high level of
      abstraction and have potentially far-reaching implications regarding the domain
      generality of structural representations.

PMID- 21873570
TI  - Maternal defense: breast feeding increases aggression by reducing stress.
AB  - Mothers in numerous species exhibit heightened aggression in defense of their
      young. This shift typically coincides with the duration of lactation in nonhuman
      mammals, which suggests that human mothers may display similarly accentuated
      aggressiveness while breast feeding. Here we report the first behavioral evidence
      for heightened aggression in lactating humans. Breast-feeding mothers inflicted
      louder and longer punitive sound bursts on unduly aggressive confederates than
      did formula-feeding mothers or women who had never been pregnant. Maternal
      aggression in other mammals is thought to be facilitated by the buffering effect
      of lactation on stress responses. Consistent with the animal literature, our
      results showed that while lactating women were aggressing, they exhibited lower
      systolic blood pressure than did formula-feeding or never-pregnant women while
      they were aggressing. Mediation analyses indicated that reduced arousal during
      lactation may disinhibit female aggression. Together, our results highlight the
      contributions of breast feeding to both protecting infants and buffering maternal
      stress.

PMID- 21873571
TI  - Stress-responsive mitogen-activated protein kinases interact with the EAR motif
      of a poplar zinc finger protein and mediate its degradation through the 26S
      proteasome.
AB  - Mitogen-activated protein kinases (MAPKs) contribute to the establishment of
      plant disease resistance by regulating downstream signaling components, including
      transcription factors. In this study, we identified MAPK-interacting proteins,
      and among the newly discovered candidates was a Cys-2/His-2-type zinc finger
      protein named PtiZFP1. This putative transcription factor belongs to a family of
      transcriptional repressors that rely on an ERF-associated amphiphilic repression
      (EAR) motif for their repression activity. Amino acids located within this
      repression motif were also found to be essential for MAPK binding. Close
      examination of the primary protein sequence revealed a functional bipartite MAPK
      docking site that partially overlaps with the EAR motif. Transient expression
      assays in Arabidopsis (Arabidopsis thaliana) protoplasts suggest that MAPKs
      promote PtiZFP1 degradation through the 26S proteasome. Since features of the
      MAPK docking site are conserved among other EAR repressors, our study suggests a
      novel mode of defense mechanism regulation involving stress-responsive MAPKs and
      EAR repressors.

PMID- 21873572
TI  - Phloem loading strategies and water relations in trees and herbaceous plants.
AB  - Most herbaceous plants employ thermodynamically active mechanisms of phloem
      loading, whereas in many trees, the mechanism is passive, by diffusion.
      Considering the different water transport characteristics of herbs and trees, we
      hypothesized that water relations play a role in the adoption of phloem loading
      strategies. We measured whole-plant hydraulic conductance (K(p)), osmolality,
      concentrations of polar metabolites, and key inorganic ions in recently mature
      leaves of 45 dicotyledonous species at midafternoon. Trees, and the few herbs
      that load passively, have low K(p), high osmolality, and high concentrations of
      transport sugars and total polar metabolites. In contrast, herbs that actively
      load sucrose alone have high K(p), low osmolality, and low concentrations of
      sugars and total polar metabolites. Solute levels are higher in sugar alcohol
      transporting species, both herbs and trees, allowing them to operate at lower
      leaf water potentials. Polar metabolites are largely responsible for leaf
      osmolality above a baseline level (approximately 300 mm) contributed by ions. The
      results suggest that trees must offset low K(p) with high concentrations of
      foliar transport sugars, providing the motivating force for sugar diffusion and
      rendering active phloem loading unnecessary. In contrast, the high K(p) of most
      herbaceous plants allows them to lower sugar concentrations in leaves. This
      reduces inventory costs and significantly increases growth potential but
      necessitates active phloem loading. Viewed from this perspective, the elevation
      of hydraulic conductance marks a major milestone in the evolution of the
      herbaceous habit, not only by facilitating water transport but also by maximizing
      carbon use efficiency and growth.

PMID- 21873573
TI  - The consequences of valproate overdose.

PMID- 21873574
TI  - Commentary.

PMID- 21873575
TI  - Commentary.

PMID- 21873576
TI  - What is your guess? A 42-year-old woman with fever after a trip to Africa.

PMID- 21873580
TI  - A community-based participatory planning process and multilevel intervention
      design: toward eliminating cardiovascular health inequities.
AB  - The elimination of persistent health inequities requires the engagement of
      multiple perspectives, resources, and skills. Community-based participatory
      research (CBPR) is one approach to developing action strategies that promote
      health equity by addressing contextual as well as individual-level factors, and
      that can contribute to addressing more fundamental factors linked to health
      inequity. Yet many questions remain about how to implement participatory
      processes that engage local insights and expertise, are informed by the existing
      public health knowledge base, and build support across multiple sectors to
      implement solutions. This article describes a CBPR approach used to conduct a
      community assessment and action planning process, culminating in development of a
      multilevel intervention to address inequalities in cardiovascular disease in
      Detroit, Michigan. The authors consider implications for future efforts to engage
      communities in developing strategies toward eliminating health inequities.

PMID- 21873581
TI  - Re: selective application of routine preoperative axillary ultrasonography
      reduces costs for invasive breast cancers.

PMID- 21873582
TI  - Disparities in underserved white populations: the case of cancer-related
      disparities in Appalachia.
AB  - There are meaningful cancer-related disparities in the Appalachian region of the
      U.S. To address these disparities, the Appalachia Community Cancer Network
      (ACCN), a collaboration of investigators and community partners in five states
      (Kentucky, Ohio, Pennsylvania, Virginia, and West Virginia), is involved in
      increasing cancer education and awareness, conducting community-based
      participatory research (CBPR), and creating mentorship and training
      opportunities. The primary objective of this paper is to describe cancer-related
      disparities in the Appalachian region of the U.S. as an example of the
      disparities experienced by underserved, predominantly white, rural populations,
      and to describe ACCN activities designed to intervene regarding these
      disparities. An ACCN overview/history and the diverse activities of ACCN
      participating states are presented in an effort to suggest potential useful
      strategies for working to reduce health-related disparities in underserved white
      populations. Strengths that have emerged from the ACCN approach (e.g., innovative
      collaborations, long-standing established networks) and remaining challenges
      (e.g., difficulties with continually changing communities, scarce resources) are
      described. Important recommendations that have emerged from the ACCN are also
      presented, including the value of allowing communities to lead CBPR efforts.
      Characteristics of the community-based work of the ACCN provide a framework for
      reducing health-related disparities in Appalachia and in other underserved white
      and rural populations.

PMID- 21873583
TI  - Cancer disparities in the context of Medicaid insurance: a comparison of survival
      for acute myeloid leukemia and Hodgkin's lymphoma by Medicaid enrollment.
AB  - BACKGROUND: Because poverty is difficult to measure, its association with
      outcomes for serious illnesses such as hematologic cancers remains largely
      uncharacterized. Using Medicaid enrollment as a proxy for poverty, we aimed to
      assess potential disparities in survival after a diagnosis of acute myeloid
      leukemia (AML) or Hodgkin's lymphoma (HL) in a nonelderly population. METHODS: We
      used records from the New York (NY) and California (CA) state cancer registries
      linked to Medicaid enrollment records for these states to identify Medicaid
      enrolled and nonenrolled patients aged 21-64 years with incident diagnoses of AML
      or HL in 2002-2006. We compared overall survival for the two groups using Kaplan
      Meier curves and Cox proportional hazards analyses adjusted for sociodemographic
      and clinical factors. RESULTS: For HL, the adjusted risk for death for Medicaid
      enrolled compared with nonenrolled patients was 1.98 (95% confidence interval
      [CI], 1.47-2.68) in NY and 1.89 (95% CI, 1.43-2.49) in CA. In contrast, for AML,
      Medicaid enrollment had no effect on survival (adjusted hazard ratio, 1.00; 95%
      CI, 0.84-1.19 in NY and hazard ratio, 1.02; 95% CI, 0.89-1.16 in CA). These
      results persisted despite adjusting for race/ethnicity and other factors.
      CONCLUSIONS: Poverty does not affect survival for AML patients but does appear to
      be associated with survival for HL patients, who, in contrast to AML patients,
      require complex outpatient treatment. Challenges for the poor in adhering to
      treatment regimens for HL could explain this disparity and merit further study.

PMID- 21873585
TI  - Autonomic and adrenocortical reactivity and buccal cell telomere length in
      kindergarten children.
AB  - OBJECTIVE: To examine associations between autonomic nervous system and
      adrenocortical reactivity to laboratory stressors and buccal cell telomere length
      (BTL) in children. METHODS: The study sample comprised 78 children, aged 5 to 6
      years, from a longitudinal cohort study of kindergarten social hierarchies,
      biologic responses to adversity, and child health. Buccal cell samples and
      reactivity measures were collected in the spring of the kindergarten year. BTL
      was measured by real-time polymerase chain reaction, as the telomere-to-single
      copy gene ratio. Parents provided demographic information; parents and teachers
      reported children's internalizing and externalizing behavior problems. Components
      of children's autonomic (heart rate, respiratory sinus arrhythmia [RSA], and
      preejection period [PEP]) and adrenocortical (salivary cortisol) responses were
      monitored during standardized laboratory challenges. We examined relationships
      between reactivity, internalizing and externalizing behaviors, and BTL, adjusted
      for age, race, and sex. RESULTS: Heart rate and cortisol reactivity were
      inversely related to BTL, PEP was positively related to BTL, and RSA was
      unrelated to BTL. Internalizing behaviors were also inversely related to BTL
      (standardized beta = -0.33, p = .004). Split at the median of reactivity
      parameters, children with high sympathetic activation (decreasing PEP), and
      parasympathetic withdrawal (decreasing RSA) did not differ with regard to BTL.
      However, children with both this profile and high cortisol reactivity (n = 12)
      had significantly shorter BTL (0.80 versus 1.00; chi2 = 7.6, p = .006), compared
      with other children. CONCLUSIONS: The combination of autonomic and adrenocortical
      reactivity was associated with shorter BTL in children. These data suggest that
      psychophysiological processes may influence, and that BTL may be a useful marker
      of, early biologic aging.

PMID- 21873588
TI  - Toward a more systematic, cumulative, and applicable science of personality and
      health: lessons from type D personality.

PMID- 21873586
TI  - Physical activity moderates effects of stressor-induced rumination on cortisol
      reactivity.
AB  - OBJECTIVE: Physically active individuals have lower rates of morbidity and
      mortality, and recent evidence indicates that physical activity may be
      particularly beneficial to those experiencing chronic stress. The tendency to
      ruminate increases and prolongs physiological stress responses, including
      hypothalamic-pituitary-adrenal (HPA) axis responses as indexed by cortisol
      reactivity to stressful experiences. We examined the association between
      ruminating in response to a laboratory stressor task and HPA axis reactivity and
      recovery and examined whether a physically active life-style moderates the
      associations between rumination and cortisol output trajectories. METHODS: Forty
      six postmenopausal women underwent the Trier Social Stress Test, whereas salivary
      cortisol was repeatedly measured. Twenty-five minutes after the end of the
      stressor, participants reported level of rumination in response to the stress.
      RESULTS: Findings indicate that physical activity moderated the initial rate (B =
      -0.10, standard error = 0.04, p < .05) and curvature (B = -0.03, standard error =
      0.01, p = .06) of the relationship between rumination and log-transformed
      cortisol trajectory. Among sedentary participants, those who responded to the
      stressor with higher levels of rumination had a more rapid initial increase in
      cortisol level (0.26 versus 0.21, p < .001), a later peak in cortisol reactivity
      (56 versus 39 minutes), and a delayed recovery from stress (curvature: -0.07
      versus -0.08, p < .001) compared with those with lower levels of rumination. In
      active participants, cortisol trajectories were equivalent, regardless of the
      level of rumination. CONCLUSIONS: In sum, individuals who maintain a physically
      active life-style may be protected against the effects of rumination on HPA axis
      reactivity to and recovery from acute stress.

PMID- 21873589
TI  - Genetic contributions to alexithymia.

PMID- 21873590
TI  - Telomere length integrates psychological factors in the successful aging story,
      but what about the biology?

PMID- 21873591
TI  - Multidimensional profiling of CSF1R screening hits and inhibitors: assessing
      cellular activity, target residence time, and selectivity in a higher throughput
      way.
AB  - Over the past years, improvements in high-throughput screening (HTS) technology
      and compound libraries have resulted in a dramatic increase in the amounts of
      good-quality screening hits, and there is a growing need for follow-on hit
      profiling assays with medium throughput to further triage hits. Here the authors
      present such assays for the colony-stimulating factor 1 receptor (CSF1R, Fms),
      including tests for cellular activity and a homogeneous assay to measure affinity
      for inactive CSF1R. They also present a high-throughput assay to measure target
      residence time, which is based on competitive binding kinetics. To better fit
      k(off) rates, they present a modified mathematical model for competitive
      kinetics. In all assays, they profiled eight reference inhibitors (imatinib,
      sorafenib, sunitinib, tandutinib, dasatinib, GW2580, Ki20227, and J&J's
      pyrido[2,3-d]pyrimidin-5-one). Using the known biochemical selectivities of these
      inhibitors, which can be quantified using metrics such as the selectivity
      entropy, the authors have determined which assay readout best predicts hit
      selectivity. Their profiling shows surprisingly that imatinib has a preference
      for the active form of CSF1R and that Ki20227 has an unusually slow target
      dissociation rate. This confirms that follow-on hit profiling is essential to
      ensure that the best hits are selected for lead optimization.

PMID- 21873592
TI  - Frailty status and altered glucose-insulin dynamics.
AB  - BACKGROUND: We examined women in their 80s and 90s and evaluated the hypothesis
      that abnormalities in the dynamic response of glucose and insulin to a glucose
      load are associated with frailty status. METHODS: We performed a 75 g oral
      glucose tolerance test in 73 community-dwelling women aged 84-95 years without
      known diabetes enrolled in the Women's Health and Aging Study II. We examined the
      association of frailty status (nonfrail, prefrail, or frail) with oral glucose
      tolerance test glucose and insulin levels at 0, 30, 60, 120, and 180 minutes
      using multiple linear regression models. RESULTS: Using American Diabetes
      Association criteria, only 27% of older women had normal glucose status, 48% had
      prediabetes, and 25% had undiagnosed diabetes. Fasting glucose, fasting insulin,
      homeostasis model of assessment-insulin resistance, and Matsuda index were
      similar by frailty status, adjusting for age and body mass index. Conversely,
      mean oral glucose tolerance test glucose levels were higher at 60 minutes (44.6
      +/- 18.1 mg/dL higher) and 120 minutes (67.1 +/- 23.5 mg/dL higher) and to a
      lesser extent at 180 minutes (44.3 +/- 22.5 mg/dL higher) in frail versus
      nonfrail women as was integrated glucose area after adjustment. Mean 120-minute
      insulin level was also higher in frail versus nonfrail women (45.7 +/- 22.4
      MUU/mL higher). Overall, glucose and insulin responses were more exaggerated and
      prolonged in frail versus nonfrail or prefrail women. CONCLUSIONS: Our data
      demonstrate dysregulation in response to glucose challenge as a component of
      physiologic vulnerability associated with frailty in old-old women. Future
      studies should examine the timing of abnormal glucose-insulin dynamics with
      respect to the pathogenesis of frailty.

PMID- 21873594
TI  - Medication ineffectiveness due to Zenker diverticulum in a compliant patient.

PMID- 21873593
TI  - Thioredoxin 1 overexpression extends mainly the earlier part of life span in
      mice.
AB  - We examined the effects of increased levels of thioredoxin 1 (Trx1) on resistance
      to oxidative stress and aging in transgenic mice overexpressing Trx1
      [Tg(TRX1)(+/0)]. The Tg(TRX1)(+/0) mice showed significantly higher Trx1 protein
      levels in all the tissues examined compared with the wild-type littermates.
      Oxidative damage to proteins and levels of lipid peroxidation were significantly
      lower in the livers of Tg(TRX1)(+/0) mice compared with wild-type littermates.
      The survival study demonstrated that male Tg(TRX1)(+/0) mice significantly
      extended the earlier part of life span compared with wild-type littermates, but
      no significant life extension was observed in females. Neither male nor female
      Tg(TRX1)(+/0) mice showed changes in maximum life span. Our findings suggested
      that the increased levels of Trx1 in the Tg(TRX1)(+/0) mice were correlated to
      increased resistance to oxidative stress, which could be beneficial in the
      earlier part of life span but not the maximum life span in the C57BL/6 mice.

PMID- 21873595
TI  - Concentration of hyaluronic acid in human vocal folds in young and old subjects.
AB  - OBJECTIVE: To compare and evaluate concentrations of hyaluronic acid (HA) in
      normal vocal folds of both young and elderly people of both sexes. STUDY DESIGN:
      Experimental study. SETTING: The research was carried out at the ENT, Head and
      Neck Surgery Department and the Pharmacology Institute of Sao Paulo Federal
      University. SUBJECTS AND METHODS: Enzyme-linked immunosorbent assay plates coated
      with biotin-conjugated binding protein and streptavidin-europium conjugate were
      sequentially incubated with samples from the middle portion of the cover, vocal
      ligament, and vocal muscle of 19 young and 20 elderly subjects of both sexes.
      After the release of europium in an enhancement solution, final fluorescence was
      measured using a fluorometer. RESULTS: Statistically significant comparisons: (1)
      all subject groups combined exhibited a higher HA concentration in the cover and
      ligament compared with the muscle samples; (2) women subjects had a significantly
      lower HA concentration in muscle compared with the ligament, and male subjects
      showed significantly lower HA in muscle compared with the cover; and (3) both
      genders of young subjects showed a higher HA concentration in ligament samples
      compared with the muscle. CONCLUSION: HA concentrations are higher in the cover
      and ligament compared with the muscle in both genders and age groups, and there
      is a higher HA concentration in ligament compared with the muscle of young
      subjects of both genders. HA levels in the cover samples of younger women showed
      great variability that may relate to ovarian hormone levels, reflecting different
      phases of the menstrual cycle.

PMID- 21873596
TI  - Otitis media: the application of personalized medicine.
AB  - During most of recorded history, the application of knowledge to the care of
      individual patients was founded on the experience of individual medical
      practitioners; when published, it basically took the form of case reports. Not
      until the middle of the 20th Century did randomized controlled trials (RCTs) come
      to be the gold standard. By the beginning of the 21st Century, however, the
      limitations of RCTs and their syntheses, the meta-analyses, have come to be
      recognized, and their applicability to the individual patient questioned and,
      indeed, challenged. The intense increase in our knowledge base and in
      accompanying technology has made possible the personalization of medicine beyond
      the possibilities of earlier periods. The approach of personalized medicine
      requires evaluation of four parameters: the individual patient's intrinsic
      susceptibility, intrinsic morbidity, extrinsic susceptibility, and extrinsic
      morbidity. The characteristics of the disease agent--how much (duration) and how
      virulent--also must be factored in. These individualized data define the
      appropriate intervention: high susceptibility and/or morbidity or low
      susceptibility and/or morbidity and the aggregate of the intrinsic and extrinsic
      risk factors are cofactored in medical decision making.

PMID- 21873597
TI  - Mammary analogue secretory carcinoma of the parotid gland in a pediatric patient.

PMID- 21873598
TI  - Intratympanic steroids for sudden sensorineural hearing loss: a systematic
      review.
AB  - OBJECTIVE: To determine the evidence for efficacy of intratympanic (IT) steroid
      treatment for the management of idiopathic sudden sensorineural hearing loss
      through a systematic review of the existing literature. DATA SOURCES: Online
      databases consisting of PubMed, Medline, OVID, Google Scholar, Cochrane Review,
      and collected additional publications cited in bibliographies. REVIEW METHODS:
      Literature search by both authors with structured criteria to select studies
      evaluated for systematic review. RESULTS: The authors identified 176 articles, of
      which 32 represented studies of initial or salvage intratympanic steroid
      injections for sudden hearing loss that included 6 randomized trials and only 2
      randomized controlled trials. Despite the paucity of well-executed trials, the
      vast majority of studies of intratympanic steroids for salvage treatment in all
      tiers demonstrated a benefit of intratympanic steroid therapy. A limited meta
      analysis of the higher quality studies revealed a mean difference in improvement
      of 13.3 dB (95% confidence interval [CI], 7.7-18.9; P < .0001). Although
      statistically significant, it is still unclear if this difference is clinically
      significant. Initial intratympanic therapy was equivalent to standard therapy in
      the existing literature of all qualities. CONCLUSION: Intratympanic steroid
      treatment as primary treatment for sudden sensorineural hearing loss appears
      equivalent to treatment with high-dose oral prednisone therapy. As salvage
      therapy, intratympanic steroids offer the potential for some degree of additional
      hearing recovery, although it remains uncertain if this improvement is clinically
      significant and what percentage of patients is likely to show benefit.

PMID- 21873599
TI  - Head and neck rhabdomyosarcoma: a critical analysis of population-based incidence
      and survival data.
AB  - OBJECTIVE: To evaluate trends in incidence, survival, and treatment of
      rhabdomyosarcoma (RMS) of the head and neck. STUDY DESIGN: Retrospective review
      of a national database. SETTING: Tertiary medical center. SUBJECT AND METHODS:
      Incidence and survival trends were examined for head and neck RMS diagnosed
      between 1973 and 2007 using the Surveillance, Epidemiology, and End Results
      Program. Frequencies, incidence rates, and relative survival curves were
      calculated for various RMS subtypes and primary sites. RESULTS: Between 1973 and
      2007, the incidence of RMS of the head and neck increased significantly, with an
      annual percentage change of 1.16%. Relative 5-year survival was statistically
      unchanged during the study period at 62.8% +/- 2.3%. When analyzed by univariate
      analysis, overall survival was found to be dependent on sex, age, primary site,
      extent of disease, and histology. When evaluated by stage, most orbital tumors
      (60.6%) presented with localized disease, while most parameningeal tumors
      presented with either regional (53.2%) or distant (28.1%) spread. Multivariate
      analysis found that age less than 10 years at diagnosis and tumors with localized
      or regional spread were associated with improved overall survival. Relative
      survival was found to be largely dependent on extent of disease rather than
      primary site. CONCLUSIONS: Despite reported advances in overall and disease-free
      survival for patients with RMS, population-based analysis shows no substantial
      improvement during the past 30+ years. The prognosis of these patients is largely
      dependent on extent of disease at diagnosis.

PMID- 21873600
TI  - Effect of adenotonsillectomy on endothelin-1 and C-reactive protein levels in
      children with sleep-disordered breathing.
AB  - OBJECTIVE: This study aimed to evaluate the influence of adenotonsillectomy on
      the plasma concentration of endothelin-1 (ET-1) and C-reactive protein (CRP) in
      children with sleep-disordered breathing (SDB). The relationship between quality
      of life and ET-1 levels was also evaluated. SETTING: Tertiary referral center.
      STUDY DESIGN: Before-and-after case series. METHODS: Fasting blood samples for ET
      1 and high-sensitivity CRP were drawn preoperatively in all patients and at 3 to
      4 months postoperatively. The Obstructive Sleep Apnea-18 (OSA-18) survey and
      Brouilette symptom score were completed by each child's parents during the same
      time periods. RESULTS: The mean ET-1 level decreased from 3.51 +/- 0.93 fmol/mL
      to 2.67 +/- 0.69 fmol/mL postoperatively (P < .01). OSA-18 survey scores and
      Brouilette symptom scores also decreased in the postoperative period (P < .01).
      When comparing moderate and severe cases to mild cases according to Brouilette
      scores, ET-1 levels were significantly higher in moderate and severe cases (P <
      .01). There was a significant correlation between ET-1 and the OSA-18 survey
      scale (r = 0.442; P = .001). Although CRP levels decreased from 0.63 +/- 1.19
      mg/dL to 0.31 +/- 0.23 mg/dL postoperatively, this was not statistically
      significant. CONCLUSION: Adenotonsillectomy effectively lowered plasma ET-1
      levels in children with SDB and thus may have reduced their related risk for
      cardiovascular disease. In addition, adenotonsillectomy improved quality of life
      in this group.

PMID- 21873601
TI  - Perfluoroalkyl chemicals and chronic kidney disease in US adults.
AB  - Chronic kidney disease (CKD) is a major public health problem. Identifying novel
      risk factors for CKD, including widely prevalent environmental exposures, is
      therefore important. Perfluoroalkyl chemicals (PFCs), including perfluorooctanoic
      acid and perfluorooctane sulfonate, are manmade chemicals that have been detected
      in the blood of more than 98% of the US population. Results from experimental
      animal studies have suggested that an association between PFCs and CKD is
      plausible. However, in humans, the relation between serum PFCs and CKD has not
      been examined. The authors examined the relation of serum PFCs and CKD in 4,587
      adult participants (51.1% women) from the combined 1999-2000 and 2003-2008 cycles
      of the National Health and Nutritional Examination Survey for whom PFC
      measurements were available. The main outcome was CKD, defined as a glomerular
      filtration rate of less than 60 mL/minute/1.73 m(2). The authors found that serum
      levels of PFCs, including perfluorooctanoic acid and perfluorooctane sulfonate,
      were positively associated with CKD. This association was independent of
      confounders such as age, sex, race/ethnicity, body mass index, diabetes,
      hypertension, and serum cholesterol level. Compared with subjects in quartile 1
      (referent), the multivariable odds ratio for CKD among subjects in quartile 4 was
      1.73 (95% confidence interval: 1.04, 2.88; P for trend = 0.015) for
      perfluorooctanoic acid and 1.82 (95% confidence interval: 1.01, 3.27; P for trend
      = 0.019) for perfluorooctane sulfonate. The present results suggest that elevated
      PFC levels are associated with CKD.

PMID- 21873602
TI  - Body mass index in young adulthood and premature death: analyses of the US
      National Health Interview Survey linked mortality files.
AB  - Knowledge of the association between body mass index (weight (kg)/height (m)(2))
      and premature death in young adulthood is very limited, especially for specific
      causes of death. Using the US National Health Interview Survey linked mortality
      files, the authors examined the relation between body mass index and premature
      death from all causes, cardiovascular disease (CVD), and cancer among 112,328
      persons aged 18-39 years who participated in the National Health Interview Survey
      in the years 1987, 1988, and 1990-1995. During an average of 16 years of follow
      up (ending on December 31, 2006), there were 3,178 deaths: 573 from CVD and 733
      from cancer. Hazard ratios and 95% confidence intervals were estimated using
      multivariate proportional hazards models adjusting for age, gender,
      race/ethnicity, education, and smoking status. In analyses restricted to
      participants who had never smoked, the hazard ratios for death from all causes
      were 1.07 (95% confidence interval (CI): 0.91, 1.26) for overweight participants,
      1.41 (95% CI: 1.16, 1.73) for obese participants, and 2.46 (95% CI: 1.91, 3.16)
      for extremely obese participants, compared with those of normal weight.
      Monotonically increasing risks for excess body weight were also observed for
      deaths from cancer and CVD. The associations found in this young cohort were much
      stronger than those in middle-aged or older populations.

PMID- 21873603
TI  - Musculoskeletal complaints among 11-year-old children and associated factors: the
      PIAMA birth cohort study.
AB  - Musculoskeletal complaints (MSC) are common among children, often persist into
      adolescence, and increase the risk of MSC in adulthood. Knowledge regarding
      determinants of MSC among children is limited. The aim of this study was to
      determine the prevalence of MSC at age 11 years and to examine associations with
      sociodemographic factors, growth and development factors, mental health,
      tiredness, and lifestyle. Data from a Netherlands birth cohort study, the
      Prevention and Incidence of Asthma and Mite Allergy (PIAMA) Study (n = 2,638),
      were used (1996-2009). MSC were defined as complaints about the back, an upper
      extremity, a lower extremity, or any of these sites. Logistic regression analyses
      using a forward stepwise procedure were performed on multiply imputed data. The 1
      year period prevalences of back, upper extremity, and lower extremity complaints
      that lasted at least 1 month were 2.8%, 4.8%, and 10.9%, respectively. Only
      poorer mental health was consistently associated with all 3 types of complaints.
      Poorer mental health, daytime tiredness, early pubertal development, being
      physically active at age 11 years, and weight-for-height z score were associated
      with having any MSC. This study showed that MSC, especially lower extremity
      complaints, are common among 11-year old-children and that only poorer mental
      health status is associated with MSC at all anatomic sites.

PMID- 21873604
TI  - Perceptual blending in odor mixtures depends on the nature of odorants and human
      olfactory expertise.
AB  - Our olfactory system is confronted with complex mixtures of odorants, often
      recognized as single entities due to odor blending (e.g., coffee). In contrast,
      we are also able to discriminate odors from complex mixtures (e.g., off-odors).
      Therefore, the olfactory system is able to engage either configural or elemental
      processes when confronted with mixtures. However, the rules that govern the
      involvement of these processes during odor perception remain poorly understood.
      In our first experiment, we examined whether simple odorant mixtures
      (binary/ternary) could elicit configural perception. Twenty untrained subjects
      were asked to evaluate the odor typicality of mixtures and their constituents.
      The results revealed a significant increase in odor typicality in some but not
      all mixtures as compared with the single components, which suggest that
      perceptual odor blending can occur only in specific mixtures (configural
      processing). In our second experiment, we tested the hypothesis that general
      olfactory expertise can improve elemental perception of mixtures. Thirty-two
      trained subjects evaluated the odor typicality of the stimuli presented during
      the first experiment, and their responses were compared with those obtained from
      the untrained panelists. The results support the idea that general training with
      odors increases the elemental perception of binary and ternary blending mixtures.

PMID- 21873605
TI  - Characterization of the interaction of interleukin-8 with hyaluronan, chondroitin
      sulfate, dermatan sulfate and their sulfated derivatives by spectroscopy and
      molecular modeling.
AB  - The interactions between glycosaminoglycans (GAGs), important components of the
      extracellular matrix, and proteins such as growth factors and chemokines play
      critical roles in cellular regulation processes. Therefore, the design of GAG
      derivatives for the development of innovative materials with bio-like properties
      in terms of their interaction with regulatory proteins is of great interest for
      tissue engineering and regenerative medicine. Previous work on the chemokine
      interleukin-8 (IL-8) has focused on its interaction with heparin and heparan
      sulfate, which regulate chemokine function. However, the extracellular matrix
      contains other GAGs, such as hyaluronic acid (HA), dermatan sulfate (DS) and
      chondroitin sulfate (CS), which have so far not been characterized in terms of
      their distinct molecular recognition properties towards IL-8 in relation to their
      length and sulfation patterns. NMR and molecular modeling have been in great part
      the methods of choice to study the structural and recognition properties of GAGs
      and their protein complexes. However, separately these methods have challenges to
      cope with the high degree of similarity and flexibility that GAGs exhibit. In
      this work, we combine fluorescence spectroscopy, NMR experiments, docking and
      molecular dynamics simulations to study the configurational and recognition
      properties of IL-8 towards a series of HA and CS derivatives and DS. We analyze
      the effects of GAG length and sulfation patterns in binding strength and
      specificity, and the influence of GAG binding on IL-8 dimer formation. Our
      results highlight the importance of combining experimental and theoretical
      approaches to obtain a better understanding of the molecular recognition
      properties of GAG-protein systems.

PMID- 21873606
TI  - Essential role of Toll-like receptor 2 in macrophage activation by glycogen.
AB  - We prepared enzymatically synthesized glycogen (ESG) with the same
      characteristics as natural glycogen and investigated whether the macrophage
      stimulating activity of glycogen was related to Toll-like receptors (TLRs), which
      are important receptors for innate immunity. ESG induced no nuclear factor-kappa
      B (NF-kappaB) activity in TLR4/MD-2/CD14-expressed human embryonic kidney 293
      (HEK293) reporter cells, whereas this polysaccharide did activate peritoneal
      exude cells (PECs) derived from TLR4-deficient mice at the same level as those
      from wild-type (WT) mice. Similarly, ESG did not activate HEK293 cells expressing
      TLR3, 5, 7, 8 or 9, suggesting that these TLRs were irrelevant to the activity of
      ESG. In contrast, ESG enhanced the NF-kappaB activity of TLR2-expressed HEK293
      reporter cells in a concentration-dependent manner. Furthermore, the cell
      stimulating activity of ESG was remarkably lower for PECs from TLR2-deficient
      mice compared with those from WT mice. The activity of ESG completely disappeared
      after treatment with a glycogen-degrading enzyme, indicating that the activity
      derived from ESG itself and not from contamination with canonical TLR2 ligands
      such as bacterial lipopeptides. Moreover, it was clarified by ELISA that ESG was
      directly bound to TLR2. Taken together, these results demonstrated that TLR2
      directly recognizes glycogen and that the recognition activates immunocytes such
      as macrophages to enhance the production of nitric oxide and inflammatory
      cytokines. In addition, it was suggested that TLR2 could be involved in the
      glycogen activity in vivo. We propose that glycogen act as an activator to
      potentiate the host defense through TLR2 on the macrophage.

PMID- 21873607
TI  - Impaired motoneuronal retrograde transport in two models of SBMA implicates two
      sites of androgen action.
AB  - Spinal and bulbar muscular atrophy (SBMA) impairs motor function in men and is
      linked to a CAG repeat mutation in the androgen receptor (AR) gene. Defects in
      motoneuronal retrograde axonal transport may critically mediate motor dysfunction
      in SBMA, but the site(s) where AR disrupts transport is unknown. We find deficits
      in retrograde labeling of spinal motoneurons in both a knock-in (KI) and a
      myogenic transgenic (TG) mouse model of SBMA. Likewise, live imaging of endosomal
      trafficking in sciatic nerve axons reveals disease-induced deficits in the flux
      and run length of retrogradely transported endosomes in both KI and TG males,
      demonstrating that disease triggered in muscle can impair retrograde transport of
      cargo in motoneuron axons, possibly via defective retrograde signaling.
      Supporting the idea of impaired retrograde signaling, we find that vascular
      endothelial growth factor treatment of diseased muscles reverses the
      transport/trafficking deficit. Transport velocity is also affected in KI males,
      suggesting a neurogenic component. These results demonstrate that androgens could
      act via both cell autonomous and non-cell autonomous mechanisms to disrupt axonal
      transport in motoneurons affected by SBMA.

PMID- 21873608
TI  - Common variants near CAV1 and CAV2 are associated with primary open-angle
      glaucoma in Caucasians from the USA.
AB  - Primary open-angle glaucoma (POAG) is a genetically complex common disease
      characterized by progressive optic nerve degeneration that results in
      irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG
      in an Icelandic population identified significant associations with single
      nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome
      7q31. In this study, we confirm that the identified SNPs are associated with POAG
      in our Caucasian US population and that specific haplotypes located in the
      CAV1/CAV2 intergenic region are associated with the disease. We also present data
      suggesting that associations with several CAV1/CAV2 SNPs are significant mostly
      in women.

PMID- 21873609
TI  - Sperm storage for cancer patients in the UK: a review of current practice.
AB  - An increasing number of cancer patients can now hope to have a full and normal
      life due to significant improvements in treatment outcomes and survival rates.
      The application of cryobiology to store fertile gametes before sterilizing
      treatments has been a natural progression. Greater awareness has markedly
      increased the worldwide demand for long-term storage of sperm, and has prompted
      the UK Human Fertilization and Embryology Authority to extend the period of
      storage permitted by their regulations to 55 years. Other patients undergoing
      sterilizing chemotherapy and/or radiotherapy such as haemoglobinopathies
      requiring bone marrow transplantation and autoimmune disorders such as rheumatoid
      arthritis may further increase the indications for sperm storage. Most adult and
      adolescent patients and their relatives/spouses/parents/guardians value this
      service even though very few eventually use the sperm. There is an urgent need to
      develop national and international guidelines for the provision, organization,
      maintenance and management of the cryopreservation services.

PMID- 21873610
TI  - Dietary advice and fruit-eating in late Tudor and early Stuart England.
AB  - This article investigates an apparent contradiction between the growth in the
      popularity of fruit-eating in late Tudor and early Stuart England, and the
      generally held contemporary medical view that many types of unprocessed fruits
      were inappropriate to a healthful diet. The first section analyzes a broad range
      of household accounts and other sources of evidence to determine the extent to
      which fruit formed part of the daily fare of the English population. The second
      section looks at the advice offered in a broad cross-section of dietaries and
      botanical works with regard to the eating of fruit. Finally, as the manners in
      which fruits were eaten are discussed, it will become clear that they could often
      be accommodated within the humoral body, and that there was less of a discrepancy
      between dietary advice and fruit-eating than may seem to be the case.

PMID- 21873611
TI  - Forests as carbon sinks--benefits and consequences.
AB  - With their ratification of the Kyoto Protocol, many countries have established
      forests on previously non-forested land with the view of offsetting greenhouse
      gas emissions. While these forests indisputably result in increased carbon
      storage in above-ground biomass, consideration of other major implications is
      often neglected. Forest establishment results in changes in albedo and soil
      carbon storage, reduced runoff and downstream water supply, and effects on
      biodiversity. Such effects of forest establishment may be less desirable from
      environmental, economic and social perspectives. While there have been many
      studies of the impacts of forest establishment on individual aspects, policy
      makers need to be able to integrate the benefits and consequences to assist in
      making decisions on land management. Further, the relative magnitude of the
      effects of forestry needs to be considered in the context of elevated atmospheric
      carbon dioxide partial pressure and climate change resulting in increasing
      temperature and changes in the amount and distribution of rainfall. This
      introductory review highlights the major benefits and consequences of forest
      establishment and demonstrates progress in integrating across the services
      provided by forests. New modelling approaches are being developed that allow
      analysis of benefits, consequences and trade-offs to assist policy makers in
      decisions to manage the provision of multiple resources.

PMID- 21873612
TI  - HIV testing among men who have sex with men (MSM): systematic review of
      qualitative evidence.
AB  - We conducted a systematic review of qualitative evidence relating to the views
      and attitudes of men who have sex with men (MSM) concerning testing for HIV.
      Studies conducted in high-income countries (Organisation for Economic Co
      operation and Development members) since 1996 were included. Seventeen studies
      were identified, most of gay or bisexual men. Data were analysed using a thematic
      analysis methodology. The uncertainty of unknown HIV status is an important
      motive for testing; however, denial is also a common response to uncertainty.
      Fear of the consequences of a positive HIV test is widespread and may take
      several forms. A sense of responsibility towards oneself or one's partner may be
      a motive for testing. The perception of stigma, from other gay men or from the
      wider culture, is a barrier to testing. Gay and other MSM have clear preferences
      regarding testing services, particularly for those that are community based,
      include non-judgemental and gay-positive service providers, and offer a high
      degree of confidentiality.

PMID- 21873613
TI  - Identifying facilitators and barriers for home injury prevention interventions
      for pre-school children: a systematic review of the quantitative literature.
AB  - Injuries are the leading cause of childhood death internationally; steep social
      gradients exist in mortality and morbidity. The majority of pre-school injuries
      occur in the home, but implementing research into practice for injury prevention
      has received little attention. This systematic review describes key facilitators
      and barriers when implementing injury prevention interventions. The review used
      articles included in a Cochrane systematic review of the effectiveness of home
      safety education, with or without the provision of safety equipment. Each paper
      was screened to ensure that children under 5 years, intervention details and
      process measures and/or barriers and facilitators were included. Two authors
      independently reviewed each paper and extracted data. Themes were identified and
      framework analysis used in an iterative process. Ninety-nine papers were
      identified, 42 excluded and 57 included in the analysis. Seven facilitators and
      six barriers were identified. Facilitators related to the approach used, focused
      messages, minimal changes, deliverer characteristics, equipment accessibility,
      behaviour change and including incentives. The barriers included complex
      interventions, cultural, socio-economic, physical and behavioural barriers and
      deliverer constraints. Barriers and facilitators should be addressed when
      implementing injury prevention interventions and studies should explicitly
      explore factors that help or hinder the process.

PMID- 21873614
TI  - Bleuler and the neurobiology of schizophrenia.
AB  - Schizophrenia remains a major challenge for psychiatry. One hundred years after
      the publication of Eugen Bleuler's monograph, we are still debating the nosology
      and mechanisms of schizophrenia. We have stalled in the development of more
      effective treatments, after success with the introduction of antipsychotic
      medication. Cure and prevention remain in the distance. This article reviews the
      importance of Bleuler's monograph for the neuroscientific exploration of
      schizophrenia. While Bleuler assumed that schizophrenia has a neural basis, he
      remained agnostic on possible mechanisms and skeptical about the value of
      pathological diagnosis. He preferred psychological understanding over neural
      explanation. He gave hope by making schizophrenia dimensional and less predictive
      of course and outcome. To make progress now, we need to redefine schizophrenia at
      the level of the brain.

PMID- 21873615
TI  - A real head turner: horizontal and vertical head directions are multichannel
      coded.
AB  - Head direction is a salient cue to the focus of other people's attention.
      Electrophysiology in macaques has shown head-selective cells in the superior
      temporal sulcus that are mostly tuned to different directions (up, down, left,
      right, front, back, etc.). However, there has been no systematic investigation
      into the visual representation of head direction in both the horizontal (left
      right) and vertical (up-down) planes in humans. We addressed whether the coding
      of head direction is best accounted for by a multichannel system, with distinct
      pools of cells (or channels) tuned to different head views (i.e., left, right,
      direct, up, and down), or an opponent-coding system with two broadly tuned pools
      of cells responding to two extremes (i.e., left-right and up-down) and "direct"
      represented as the equilibrium state in the system. In a series of four
      experiments, we carried out two adaptation procedures for which multichannel and
      opponent coding predict distinct outcomes. The results support multichannel
      coding of head direction in both the vertical and horizontal axes.

PMID- 21873616
TI  - The role of brightness and orientation congruence in the perception of surface
      gloss.
AB  - The perception of surface gloss depends on specular highlights but little is
      understood about how the visual system distinguishes specular highlights from
      other luminance maxima generated by variations in pigmentation or illumination.
      It has been argued that diffuse shading gradients provide information for
      identifying specular highlights. Specular highlights typically share the
      orientation of the diffuse shading locally. Specular highlights are typically
      proximal to the brightest region of the diffuse shading locally. We compared the
      contributions of these two relationships to perceived gloss. Highlight
      orientation relative to the diffuse shading was varied by rotating highlights.
      Highlight distance from the brightest region of the diffuse shading was varied by
      translating highlights in displays that preserved the orientations of highlights
      relative to their surrounds. Both manipulations reduced perceived gloss.
      Rotations reduced perceived gloss more than translations, even though
      translations displaced highlights into darker regions than rotations. The same
      reductions in perceived gloss occurred when highlights were matched in perceived
      contrast across conditions (Experiment 2b). The results provide evidence that the
      perception of gloss depends on highlight distance from the luminance maxima of
      the surrounding intensity gradient (brightness congruence) in addition to the
      shared orientation of highlights with their surrounds (orientation congruence).

PMID- 21873617
TI  - Nonlinear summation really can be used to perform AND operations: reply to May
      and Zhaoping.

PMID- 21873618
TI  - Laser stimulation of the chloroplast/endoplasmic reticulum nexus in tobacco
      transiently produces protein aggregates (boluses) within the endoplasmic
      reticulum and stimulates local ER remodeling.
AB  - Does the ER subdomain that associates with the chloroplast in vivo, hereafter
      referred to as the chloroplast/ER nexus, play a role in protein flow within the
      ER? In studies of tobacco cells either constitutively or transiently expressing
      ER-retained luminal, GFP-HDEL, or trans-membrane, YFP-RHD3, fluorescent fusion
      proteins, brief 405-nm (3-6-mW) laser stimulation of the nexus causes a
      qualitative difference in the movement and behavior of proteins in the ER.
      Photostimulating the nexus produces fluorescent protein punctate aggregates
      (boluses) within the lumen and membrane of the ER. The aggregation propagates
      through the membrane network throughout the cell, but within minutes can revert
      to normal, with disaggregation propagating back toward the originally
      photostimulated nexus. In the meantime, the ER grows and anastomoses around the
      chloroplast, forming a dense cisternal and tubular network. If this network is
      again photostimulated, bolus formation does not recur and, if the
      photostimulation results in photobleaching, fluorescence recovery after
      photobleaching occurs as it would typically in areas away from the nexus. Bolus
      propagation is not mediated by the actin cytoskeleton, but can be reversed by pre
      conditioning the cells for 30  min with high, 40-45 degrees C, temperature (heat
      stress). Because it is not reversed with heat stress, the reorganization of the
      ER at the nexus following photostimulation is a separate event.

PMID- 21873619
TI  - Fitting into the harsh reality: regulation of iron-deficiency responses in
      dicotyledonous plants.
AB  - Iron is an essential element for life on Earth and its shortage, or excess, in
      the living organism may lead to severe health disorders. Plants serve as the
      primary source of dietary iron and improving crop iron content is an important
      step towards a better public health. Our review focuses on the control of iron
      acquisition in dicotyledonous plants and monocots that apply a reduction-based
      strategy in order to mobilize and import iron from the rhizosphere. Achieving a
      balance between shortage and excess of iron requires a tight regulation of the
      activity of the iron uptake system. A number of studies, ranging from single gene
      characterization to systems biology analyses, have led to the rapid expansion of
      our knowledge on iron uptake in recent years. Here, we summarize the novel
      insights into the regulation of iron acquisition and internal mobilization from
      intracellular stores. We present a detailed view of the main known regulatory
      networks defined by the Arabidopsis regulators FIT and POPEYE (PYE).
      Additionally, we analyze the root and leaf iron-responsive regulatory networks,
      revealing novel potential gene interactions and reliable iron-deficiency marker
      genes. We discuss perspectives and open questions with regard to iron sensing and
      post-translational regulation.

PMID- 21873620
TI  - Comparative outcomes of treated symptomatic versus non-treated asymptomatic high
      grade central vein stenoses in the outflow of predominantly dialysis fistulas.
AB  - BACKGROUND: Witholding treatment in asymptomatic/pauci-symptomatic high-grade
      central vein stenosis (CVS), i.e. those not causing debilitating painful
      extremity oedema, the benefits of which have been shown in only one study in
      grafts, is debatable. The aim of our study was to assess the short- and long-term
      benefits of such a strategy in mainly autogenous fistulas. METHODS: We
      retrospectively compared the outcomes of 53 untreated asymptomatic/pauci
      symptomatic and 50 symptomatic high-grade CVS treated by dilation with or without
      stenting between January 1998 and August 2010 at a single center. Central vein
      and access patency was estimated by Kaplan-Meier analysis. RESULTS: Mean age,
      central catheter use and location of stenosis (brachiocephalic vein) in
      asymptomatic/pauci-symptomatic and symptomatic CVS were significantly different
      at 69 versus 75 years, 28 versus 48% and 74 versus 56%, respectively. Ninety
      percent of the cases had an autogenous fistula. The mean degree of stenosis was
      >80%. Fourty percent of asymptomatic/pauci-symptomatic CVS became severely
      symptomatic after 4 years. Primary central vein patency at 3, 12, 24 and 36
      months in asymptomatic/pauci-symptomatic and symptomatic CVS were 87+/-5 versus
      82+/-6, 77+/-6 versus 55+/-9, 71+/-7 versus 35+/-9 and 67+/-7 versus 18+/-9%,
      respectively (P=0.002). Primary access circuit patency rate was not significantly
      different between the two groups with 66+/-5 versus 50+/-4% at 1 year. Secondary
      central vein and access circuit patency rates at 1 and 3 years were 100 and 93+/
      7 versus 89+/-5 and 84+/-7% (P=0.014). CONCLUSIONS: Withholding treatment in
      asymptomatic/pauci-symptomatic CVS in dialysis fistulas yielded significantly
      better short- and long-term central vein patency than treatment of symptomatic
      cases without detrimental effects on overall dialysis circuit.

PMID- 21873621
TI  - Beta-blockers and cardiovascular outcomes in dialysis patients: a cohort study in
      Ontario, Canada.
AB  - BACKGROUND: Beta-blockers may be cardioprotective in patients receiving chronic
      dialysis. We examined cardiovascular outcomes among incident dialysis patients
      receiving beta-blocker therapy. METHODS: We conducted a retrospective cohort
      study employing linked healthcare databases in Ontario, Canada. We studied all
      consecutive chronic dialysis patients aged>=66 years who initiated dialysis
      between 1 July 1991 and 31 July 2007. Patients were divided into three groups
      according to new medication use after the initiation of chronic dialysis. The
      three groups were patients initiated on beta-blockers, calcium channel blockers
      and statins only. Patients in the beta-blocker and calcium channel blocker groups
      could also be concurrently receiving a statin. The primary outcome was time to a
      composite endpoint of death, myocardial infarction, stroke or coronary
      revascularization. RESULTS: There were a total of 1836 patients (504 beta
      blocker, 570 calcium channel blocker and 762 statin-only users). Compared to
      statin-only use, beta-blocker use was not associated with improved cardiovascular
      outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92
      1.23]. As expected, calcium channel blocker use was also not associated with
      improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79-1.06). Among all subgroup
      analyses by beta-blocker attributes, only high-dose beta-blocker therapy was
      associated with better cardiovascular outcomes as compared to low-dose beta
      blockers (aHR 0.50, 95% CI 0.29-0.88). CONCLUSIONS: We observed no beneficial
      effect of beta-blocker use among patients receiving chronic dialysis relative to
      our comparator groups. Given current uncertainty around the cardioprotective
      benefits of beta-blockers in patients receiving dialysis, a large randomized
      clinical trial is warranted.

PMID- 21873622
TI  - Chronic renal failure is accompanied by endothelial activation and a large
      increase in microparticle numbers with reduced procoagulant capacity.
AB  - BACKGROUND: In patients with chronic renal failure (CRF), cardiovascular disease
      is the leading cause of increased morbidity and mortality. We hypothesized a role
      for endothelial activation and microparticle (MP) numbers and procoagulant
      activity in the pre-thrombotic state of these patients. METHODS: We analysed
      blood samples of 27 patients with CRF [8 chronic kidney disease Stage 4 (CKD4), 9
      peritoneal dialysis (PD) and 10 haemodialysis (HD), samples taken before and
      after HD] and 10 controls. Degree and nature of endothelial activation were
      assessed by measuring mature von Willebrand factor (vWF) and vWF propeptide
      levels. Cellular MPs were characterized by flow cytometry and MP-specific
      thrombin generation (TG) measurements. RESULTS: CRF was accompanied by chronic
      (CKD4 and PD) or acute (HD) endothelial activation. Patients with CRF had
      substantially higher MP numbers than controls (median 9400 versus 4350*10(6)/L,
      P=0.001), without significant differences between the treatment subgroups or
      between pre- and post-HD. The vast majority of MPs were platelet derived. Of the
      minor populations, endothelial MPs and tissue factor-bearing MPs were more
      abundant in CRF. MPs were procoagulant, but the increase in numbers was not
      reflected in a proportional increase in MP-specific TG. CONCLUSION: Renal failure
      is accompanied by endothelial activation of a different nature in CKD4 and PD
      patients compared to HD patients, and results in all subgroups in an increase of
      mainly platelet-derived MPs that appear to be less procoagulant than in other
      disease states, possibly because of the uraemic functional defect of their
      cellular source.

PMID- 21873624
TI  - Changes in causes of death and risk of cancer in Danish patients with autosomal
      dominant polycystic kidney disease and end-stage renal disease.
AB  - BACKGROUND: With the improved prognosis in patients with autosomal dominant
      polycystic kidney disease (ADPKD), causes of death and the risk of cancer might
      have changed. This was investigated in a Danish population with ADPKD and end
      stage renal disease (ESRD) between 1 January 1993 and 31 December 2008. METHODS:
      Data were retrieved from three Danish national registries and a total of 823
      patients were identified of which 431 had died during the study period. The 16
      years were divided into two 8-year periods and the causes of death were divided
      into six categories: cancer, cardiovascular, cerebrovascular, infection, other
      and unknown. RESULTS: Cardiovascular disease was the major cause of death. A
      multivariate competing risk model comparing the two 8-year periods, adjusted for
      age at ESRD, gender and treatment modality, showed that deaths from
      cardiovascular disease decreased by 35% [hazard ratios (HR) 0.65, P=0.008] and
      deaths from cerebrovascular disease decreased by 69% (HR 0.31, P=0.0003) from the
      first to the second time period. There were no significant changes between the
      time periods in death from cancer, infection, other or unknown. From the first to
      the second 8-year interval, the prevalence of cancer increased by 35% (P=0.0002)
      while the cancer incidence was stable. CONCLUSIONS: In Danish patients with ADPKD
      and ESRD, there was a significant reduction in cardiovascular and cerebrovascular
      deaths from 1993 to 2008. The prevalence of cancer increased without significant
      change in cancer incidence or deaths from cancer.

PMID- 21873623
TI  - Deletion of the Cl-/HCO3- exchanger pendrin downregulates calcium-absorbing
      proteins in the kidney and causes calcium wasting.
AB  - BACKGROUND: The epithelial calcium channel (ECaC) (TRPV5) and the Cl-/HCO3-
      exchanger pendrin (SLC26A4) are expressed on the apical membrane of tubular cells
      in the distal nephron and play essential roles in calcium re-absorption and
      bicarbonate secretion, respectively, in the kidney. METHODS: A combination of
      functional and molecular biology techniques were employed to examine the role of
      pendrin deletion in calcium excretion. RESULTS: Here, we demonstrate that
      deletion of pendrin causes acidic urine [urine pH 4.9 in knockout (KO) versus 5.9
      in wild-type (WT) mice, P<0.03)] and downregulates the calcium-absorbing
      molecules ECaC and Na/Ca exchanger in the kidney, as shown by northern
      hybridization, immunoblot analysis and/or immunofluorescent labeling. These
      changes were associated with a ~100% increase in 24-h urine calcium excretion in
      pendrin null mice. Subjecting the pendrin WT and KO mice to oral bicarbonate
      loading for 12 days increased the urine pH to ~8 in both genotypes, normalized
      the expression of ECaC and Na/Ca exchanger and reduced the urine calcium
      excretion in pendrin-null mice to levels comparable to WT mice. CONCLUSIONS: We
      suggest that pendrin dysfunction should be suspected and investigated in humans
      with an otherwise unexplained acidic urine and hypercalciuria.

PMID- 21873625
TI  - Victoria Stroop Test: normative data in a sample group of older people and the
      study of their clinical applications in the assessment of inhibition in
      Alzheimer's disease.
AB  - The Stroop Color-Word Test-Victoria version (VST) is a measure of executive
      function commonly used in neuropsychological evaluation. Because of its short
      administration time, the VST seems particularly appropriate for use in geriatric
      populations and with those suffering from dementia and who are prone to fatigue
      during neuropsychological examination. In this study, we examine the influence of
      demographic characteristics on VST score and present descriptive data for a
      sample of 244 elderly French speakers (50-94 years of age). Normative data
      corrected for age and education are provided for clinical use. Furthermore, by
      comparing the VST performance of patients with the Alzheimer-type dementia to
      that of 40 matched healthy controls, we provide clinical evidence suggesting that
      the VST has a clinical utility in the assessment of inhibition in AD.

PMID- 21873626
TI  - Higher rates to reduce irregularity: the use of overdrive pacing in atrial
      fibrillation.

PMID- 21873627
TI  - Trans-venous lead removal without the use of extraction sheaths, results of >250
      removal procedures.
AB  - AIMS: The number of implanted cardiac rhythm devices has rapidly increased in the
      past decade. Subsequently, the need for lead extraction has also increased.
      Several techniques of lead removal have been documented from manual traction of
      the lead to lead extraction assisted with mechanical or laser sheaths. The goal
      of this study was to review our experience with lead removal using manual
      traction without the assistance of extraction sheaths. METHODS AND RESULTS: In
      the Leiden University Medical Center all leads are removed using manual traction
      without the assistance of extraction sheaths. We have retrospectively reviewed
      all lead removal procedures performed between 2000 and 2009. Procedures were
      reviewed for indication, success, complication rates, and mortality. In total,
      279 lead removal procedures were included. During these procedures 445 leads were
      removed. Time since lead implantation: 4.2 +/- 4.7 years. During extraction
      53(11.9%) leads fractured, of which >50% could still be completely removed using
      a femoral approach. A longer implantation duration [odds ratio (OR) 1.16 per
      year, 95% confidence interval (CI) 1.09-1.23] and passive fixation (OR 2.52,
      95%CI 1.17-5.45) significantly associated with the chance of lead fracture during
      lead removal. Clinical success, using the primary approach of manual traction
      from the pectoral area, was obtained in 228 (84.8%) procedures. Major
      complications occurred in 2(0.7%) and minor in 13(4.7%) procedures. One patient
      died within 24 h after the procedure due to septic shock. There was no further
      mortality within the first month after the procedure. CONCLUSION: Lead removal
      using manual traction, without the assistance of lead extraction sheaths, is
      clinically successful in ~85% of the lead extraction procedures. Concomitant
      morbidity and mortality are low. The highest clinical success (~95%) was observed
      in patients with leads implanted less than 2.6 years.

PMID- 21873628
TI  - Intramural inflammation as a cause of transient ST-segment elevation in a patient
      of cardiac sarcoidosis.
AB  - Cardiac magnetic resonance demonstrated myocardial damage within the left
      ventricle (LV) in a patient with cardiac sarcoidosis. During inflammation, ST
      segment elevation was observed in her ECG. The ST-segment deviation was
      attenuated following disappearance of the abnormal Gallium-67 uptake in the LV,
      suggesting transmural LV voltage gradient was a cause of the ST-segment
      elevation.

PMID- 21873629
TI  - A modified subcutaneous implantable cardioverter-defibrillator implant in a
      patient with a previous left ventricular epicardial defibrillation patch.
AB  - We describe a case of subcutaneous implantable cardioverter-defibrillator (ICD)
      implant in a patient with an existing epicardial defibrillation patch. Potential
      issues with shock vector shielding were overcome by a modification of the
      generator implant site and poor sensing were successfully managed by programming
      a sensing vector which excluded the generator.

PMID- 21873630
TI  - Zisupton--a novel superfamily of DNA transposable elements recently active in
      fish.
AB  - Transposable elements are widespread mobile DNA sequences able to integrate into
      new locations within genomes. Through transposition and recombination, they
      significantly contribute to genome plasticity and evolution. They can also
      regulate gene expression and provide regulatory and coding sequences (CDSs) for
      the evolution of novel gene functions. We have identified a new superfamily of
      DNA transposon on the Y chromosome of the platyfish Xiphophorus maculatus. This
      element is 11 kb in length and carries a single CDS of 24 exons. The N-terminal
      part of the putative protein, which is expressed in all adult tissues tested,
      contains several nucleic acid- and protein-binding domains and might correspond
      to a novel type of transposase/integrase not described so far in any transposon.
      In addition, a testis-specific splice isoform encodes a C-terminal Ulp1 SUMO
      protease domain, suggesting a function in posttranslational protein modification
      mediated by SUMO and/or ubiquitin small peptides. Accordingly, this element was
      called Zisupton, for Zinc finger SUMO protease transposon. Beside the Y
      chromosomal sequence, five other very similar copies were identified in the
      platyfish genome. All copies are delimited by 99-bp conserved subterminal
      inverted repeats and flanked by copy-specific 8-nt target site duplications
      reflecting their integration at different positions in the genome. Zisupton
      elements are inserted at different genomic locations in different poeciliid
      species but also in different populations of X. maculatus. Such insertion
      polymorphisms between related species and populations indicate relatively recent
      transposition activity, with a high degree of nucleotide identity between species
      suggesting possible implication of horizontal gene transfer. Zisupton sequences
      were detected in other fish species, in urochordates, cephalochordates, and
      hemichordates as well as in more distant organisms, such as basidiomycete fungi,
      filamentous brown algae, and green algae. Possible examples of nuclear genes
      derived from Zisupton have been identified. To conclude, our analysis has
      uncovered a new superfamily of DNA transposons with potential roles in genome
      diversity and evolutionary innovation in fish and other organisms.

PMID- 21873631
TI  - Tissue-specific alternative splicing of Tak1 is conserved in deuterostomes.
AB  - Alternative splicing allows organisms to rapidly modulate protein functions to
      physiological changes and therefore represents a highly versatile adaptive
      process. We investigated the conservation of the evolutionary history of the
      "Fox" family of RNA-binding splicing factors (RBFOX) as well as the conservation
      of regulated alternative splicing of the genes they control. We found that the
      RBFOX proteins are conserved in all metazoans examined. In humans, Fox proteins
      control muscle-specific alternative splicing of many genes but despite the
      conservation of splicing factors, conservation of regulation of alternative
      splicing has never been demonstrated between man and nonvertebrate species.
      Therefore, we studied 40 known Fox-regulated human exons and found that 22 had a
      tissue-specific splicing pattern in muscle and heart. Of these, 11 were spliced
      in the same tissue-specific manner in mouse tissues and 4 were tissue
      specifically spliced in muscle and heart of the frog Xenopus laevis. The
      inclusion of two of these alternative exons was also downregulated during tadpole
      development. Of the 40 in the starting set, the most conserved alternative
      splicing event was in the transforming growth factor (TGF) beta-activated kinase
      Tak1 (MAP3K7) as this was also muscle specific in urochordates and in
      Ambulacraria, the most ancient deuterostome clade. We found exclusion of the
      muscle-specific exon of Tak1 was itself under control of TGF beta in cell culture
      and consistently that TGF beta caused an upregulation of Fox2 (RBFOX2)
      expression. The alternative exon, which codes for an in-frame 27 amino acids
      between the kinase and known regulatory domain of TAK1, contains conserved
      features in all organisms including potential phosphorylation sites and likely
      has an important conserved function in TGF beta signaling and development. This
      study establishes that deuterostomes share a remarkable conserved physiological
      process that involves a splicing factor and expression of tissue-specific
      isoforms of a target gene that expedites a highly conserved signaling pathway.

PMID- 21873632
TI  - Impact of preoperative maintenance or interruption of aspirin on thrombotic and
      bleeding events after elective non-cardiac surgery: the multicentre, randomized,
      blinded, placebo-controlled, STRATAGEM trial.
AB  - BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular
      prevention frequently require non-cardiac surgery. A substantial proportion of
      these patients have their anti-platelet drug discontinued before operation;
      however, there is uncertainty about the impact of this practice. The aim of this
      study was to compare the effect of maintenance or interruption of aspirin before
      surgery, in terms of major thrombotic and bleeding events. METHODS: Patients
      treated with anti-platelet agents for secondary prevention and undergoing
      intermediate- or high-risk non-cardiac surgery were included in this multicentre,
      randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets
      with aspirin (75 mg daily) or placebo starting 10 days before surgery. The
      primary outcome was a composite score evaluating both major thrombotic and
      bleeding adverse events occurring within the first 30 postoperative days weighted
      by their severity (weights were established a priori using a Delphi consensus
      process). Analyses followed the intention-to-treat principle. RESULTS: We
      randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The
      most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal
      surgery (20.6%), and urologic surgery (15.5%). No significant difference was
      observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in
      the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in
      the number of major complications between groups. CONCLUSIONS: In these at-risk
      patients undergoing elective non-cardiac surgery, we did not find any difference
      in terms of occurrence of major thrombotic or bleeding events between
      preoperative maintenance or interruption of aspirin.

PMID- 21873633
TI  - Arteriovenous malformation: a rare cause of trigeminal neuralgia identified by
      magnetic resonance imaging with constructive interference in steady state
      sequences.

PMID- 21873634
TI  - The use of enriched 6Li and 7Li Lif:Mg,Cu,P glass-rod thermoluminescent
      dosemeters for linear accelerator out-of-field radiation dose measurements.
AB  - (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescent dosemeters (TLDs)
      were used for measurements of out-of-field photon and neutron doses produced by
      Varian iX linear accelerator. Both TLDs were calibrated using 18-MV X-ray beam to
      investigate their dose-response sensitivity and linearity. CR-39 etch-track
      detectors (Luxel+, Landauer) were employed to provide neutron dose data to
      calibrate (6)LiF:Mg,Cu,P TLDs at various distances from the isocentre. With
      cadmium filters employed, slow neutrons (<0.5 eV) were distinguished from fast
      neutrons. The average in-air photon dose equivalents per monitor unit (MU) ranged
      from 1.5+/-0.4 to 215.5+/-94.6 MUSv at 100 and 15 cm from the isocentre,
      respectively. Based on the cross-calibration factors obtained with CR-39 etch
      track detectors, the average in-air fast neutron dose equivalents per MU range
      from 10.6+/-3.8 to 59.1+/-49.9 MUSv at 100 and 15 cm from the isocentre,
      respectively. Contribution of thermal neutrons to total neutron dose equivalent
      was small: 3.1+/-7.2 MUSv per MU at 15 cm from the isocentre.

PMID- 21873635
TI  - Phylogenetic-based propagation of functional annotations within the Gene Ontology
      consortium.
AB  - The goal of the Gene Ontology (GO) project is to provide a uniform way to
      describe the functions of gene products from organisms across all kingdoms of
      life and thereby enable analysis of genomic data. Protein annotations are either
      based on experiments or predicted from protein sequences. Since most sequences
      have not been experimentally characterized, most available annotations need to be
      based on predictions. To make as accurate inferences as possible, the GO
      Consortium's Reference Genome Project is using an explicit evolutionary framework
      to infer annotations of proteins from a broad set of genomes from experimental
      annotations in a semi-automated manner. Most components in the pipeline, such as
      selection of sequences, building multiple sequence alignments and phylogenetic
      trees, retrieving experimental annotations and depositing inferred annotations,
      are fully automated. However, the most crucial step in our pipeline relies on
      software-assisted curation by an expert biologist. This curation tool,
      Phylogenetic Annotation and INference Tool (PAINT) helps curators to infer
      annotations among members of a protein family. PAINT allows curators to make
      precise assertions as to when functions were gained and lost during evolution and
      record the evidence (e.g. experimentally supported GO annotations and
      phylogenetic information including orthology) for those assertions. In this
      article, we describe how we use PAINT to infer protein function in a phylogenetic
      context with emphasis on its strengths, limitations and guidelines. We also
      discuss specific examples showing how PAINT annotations compare with those
      generated by other highly used homology-based methods.

PMID- 21873636
TI  - iMod: multipurpose normal mode analysis in internal coordinates.
AB  - MOTIVATION: Dynamic simulations of systems with biologically relevant sizes and
      time scales are critical for understanding macromolecular functioning. Coarse
      grained representations combined with normal mode analysis (NMA) have been
      established as an alternative to atomistic simulations. The versatility and
      efficiency of current approaches normally based on Cartesian coordinates can be
      greatly enhanced with internal coordinates (IC). RESULTS: Here, we present a new
      versatile tool chest to explore conformational flexibility of both protein and
      nucleic acid structures using NMA in IC. Consideration of dihedral angles as
      variables reduces the computational cost and non-physical distortions of
      classical Cartesian NMA methods. Our proposed framework operates at different
      coarse-grained levels and offers an efficient framework to conduct NMA-based
      conformational studies, including standard vibrational analysis, Monte-Carlo
      simulations or pathway exploration. Examples of these approaches are shown to
      demonstrate its applicability, robustness and efficiency. CONTACT:
      pablo@chaconlab.org SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 21873637
TI  - Spatial clustering of protein binding sites for template based protein docking.
AB  - MOTIVATION: In recent years, much structural information on protein domains and
      their pair-wise interactions has been made available in public databases.
      However, it is not yet clear how best to use this information to discover general
      rules or interaction patterns about structural protein-protein interactions.
      Improving our ability to detect and exploit structural interaction patterns will
      help to provide a better 3D picture of the known protein interactome, and will
      help to guide docking-based predictions of the 3D structures of unsolved protein
      complexes. RESULTS: This article presents KBDOCK, a 3D database approach for
      spatially clustering protein binding sites and for performing template-based
      (knowledge-based) protein docking. KBDOCK combines residue contact information
      from the 3DID database with the Pfam protein domain family classification
      together with coordinate data from the Protein Data Bank. This allows the 3D
      configurations of all known hetero domain-domain interactions to be superposed
      and clustered for each Pfam family. We find that most Pfam domain families have
      up to four hetero binding sites, and over 60% of all domain families have just
      one hetero binding site. The utility of this approach for template-based docking
      is demonstrated using 73 complexes from the Protein Docking Benchmark. Overall,
      up to 45 out of 73 complexes may be modelled by direct homology to existing
      domain interfaces, and key binding site information is found for 24 of the 28
      remaining complexes. These results show that KBDOCK can often provide useful
      information for predicting the structures of unknown protein complexes.
      AVAILABILITY: http://kbdock.loria.fr/ CONTACT: Dave.Ritchie@inria.fr
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21873638
TI  - Feature-based 3D motif filtering for ribosomal RNA.
AB  - MOTIVATION: RNA 3D motifs are recurrent substructures in an RNA subunit and are
      building blocks of the RNA architecture. They play an important role in binding
      proteins and consolidating RNA tertiary structures. RNA 3D motif searching
      consists of two steps: candidate generation and candidate filtering. We proposed
      a novel method, known as Feature-based RNA Motif Filtering (FRMF), for
      identifying motifs based on a set of moment invariants and the Earth Mover's
      Distance in the second step. RESULTS: A positive set of RNA motifs belonging to
      six characteristic types, with eight subtypes occurring in HM 50S, is compiled by
      us. The proposed method is validated on this representative set. FRMF
      successfully finds most of the positive fragments. Besides the proposed new
      method and the compiled positive set, we also recognize some new motifs, in
      particular a pi-turn and some non-standard A-minor motifs are found. These newly
      discovered motifs provide more information about RNA structure conformation.
      AVAILABILITY: Matlab code can be downloaded from
      www.cs.cityu.edu.hk/~yingshen/FRMF.html CONTACT: cshswong@cityu.edu.hk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21873639
TI  - SCLpred: protein subcellular localization prediction by N-to-1 neural networks.
AB  - SUMMARY: Knowledge of the subcellular location of a protein provides valuable
      information about its function and possible interaction with other proteins. In
      the post-genomic era, fast and accurate predictors of subcellular location are
      required if this abundance of sequence data is to be fully exploited. We have
      developed a subcellular localization predictor (SCLpred), which predicts the
      location of a protein into four classes for animals and fungi and five classes
      for plants (secreted, cytoplasm, nucleus, mitochondrion and chloroplast) using
      machine learning models trained on large non-redundant sets of protein sequences.
      The algorithm powering SCLpred is a novel Neural Network (N-to-1 Neural Network,
      or N1-NN) we have developed, which is capable of mapping whole sequences into
      single properties (a functional class, in this work) without resorting to
      predefined transformations, but rather by adaptively compressing the sequence
      into a hidden feature vector. We benchmark SCLpred against other publicly
      available predictors using two benchmarks including a new subset of Swiss-Prot
      Release 2010_06. We show that SCLpred surpasses the state of the art. The N1-NN
      algorithm is fully general and may be applied to a host of problems of similar
      shape, that is, in which a whole sequence needs to be mapped into a fixed-size
      array of properties, and the adaptive compression it operates may shed light on
      the space of protein sequences. AVAILABILITY: The predictive systems described in
      this article are publicly available as a web server at
      http://distill.ucd.ie/distill/. CONTACT: gianluca.pollastri@ucd.ie.

PMID- 21873640
TI  - Fast and accurate prediction of protein side-chain conformations.
AB  - SUMMARY: We developed a fast and accurate side-chain modeling program [Optimized
      Side Chain Atomic eneRgy (OSCAR)-star] based on orientation-dependent energy
      functions and a rigid rotamer model. The average computing time was 18 s per
      protein for 218 test proteins with higher prediction accuracy (1.1% increase for
      chi(1) and 0.8% increase for chi(1+2)) than the best performing program developed
      by other groups. We show that the energy functions, which were calibrated to
      tolerate the discrete errors of rigid rotamers, are appropriate for protein loop
      selection, especially for decoys without extensive structural refinement.
      AVAILABILITY: OSCAR-star and the 218 test proteins are available for download at
      http://sysimm.ifrec.osaka-u.ac.jp/OSCAR  CONTACT:  standley@ifrec.osaka-u.ac.jp
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21873641
TI  - Extending KNIME for next-generation sequencing data analysis.
AB  - SUMMARY: KNIME (Konstanz Information Miner) is a user-friendly and comprehensive
      open-source data integration, processing, analysis and exploration platform. We
      present here new functionality and workflows that open the door to performing
      next-generation sequencing analysis using the KNIME framework. AVAILABILITY: All
      sources and compiled code are available via the KNIME update mechanism. Example
      workflows and descriptions are available through
      http://tech.knime.org/community/next-generation-sequencing. CONTACT:
      bernd.jagla@pasteur.fr SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21873642
TI  - COCOMAPS: a web application to analyze and visualize contacts at the interface of
      biomolecular complexes.
AB  - SUMMARY: Herein we present COCOMAPS, a novel tool for analyzing, visualizing and
      comparing the interface in protein-protein and protein-nucleic acids complexes.
      COCOMAPS combines traditional analyses and 3D visualization of the interface with
      the effectiveness of intermolecular contact maps. AVAILABILITY: COCOMAPS is
      accessible as a public web tool at http://www.molnac.unisa.it/BioTools/cocomaps
      CONTACT: romina.oliva@uniparthenope.it; lcavallo@unisa.it.

PMID- 21873643
TI  - Predicting the distribution and ecological niche of unexploited snow crab
      (Chionoecetes opilio) populations in Alaskan waters: a first open-access ensemble
      model.
AB  - Populations of the snow crab (Chionoecetes opilio) are widely distributed on high
      latitude continental shelves of the North Pacific and North Atlantic, and
      represent a valuable resource in both the United States and Canada. In US waters,
      snow crabs are found throughout the Arctic and sub-Arctic seas surrounding
      Alaska, north of the Aleutian Islands, yet commercial harvest currently focuses
      on the more southerly population in the Bering Sea. Population dynamics are well
      monitored in exploited areas, but few data exist for populations further north
      where climate trends in the Arctic appear to be affecting species' distributions
      and community structure on multiple trophic levels. Moreover, increased shipping
      traffic, as well as fisheries and petroleum resource development, may add
      additional pressures in northern portions of the range as seasonal ice cover
      continues to decline. In the face of these pressures, we examined the ecological
      niche and population distribution of snow crabs in Alaskan waters using a GIS
      based spatial modeling approach. We present the first quantitative open-access
      model predictions of snow-crab distribution, abundance, and biomass in the
      Chukchi and Beaufort Seas. Multi-variate analysis of environmental drivers of
      species' distribution and community structure commonly rely on multiple linear
      regression methods. The spatial modeling approach employed here improves upon
      linear regression methods in allowing for exploration of nonlinear relationships
      and interactions between variables. Three machine-learning algorithms were used
      to evaluate relationships between snow-crab distribution and environmental
      parameters, including TreeNet, Random Forests, and MARS. An ensemble model was
      then generated by combining output from these three models to generate consensus
      predictions for presence-absence, abundance, and biomass of snow crabs. Each
      algorithm identified a suite of variables most important in predicting snow-crab
      distribution, including nutrient and chlorophyll-a concentrations in overlying
      waters, temperature, salinity, and annual sea-ice cover; this information may be
      used to develop and test hypotheses regarding the ecology of this species. This
      is the first such quantitative model for snow crabs, and all GIS-data layers
      compiled for this project are freely available from the authors, upon request,
      for public use and improvement.

PMID- 21873644
TI  - An integrated multi-disciplinary approach for studying multiple stressors in
      freshwater ecosystems: Daphnia as a model organism.
AB  - The increased overexploitation of freshwater ecosystems and their extended
      watersheds often generates a cascade of anthropogenic stressors (e.g.,
      acidification, eutrophication, metal contamination, Ca decline, changes in the
      physical environment, introduction of invasive species, over-harvesting of
      resources). The combined effect of these stressors is particularly difficult to
      study, requiring a coordinated multi-disciplinary effort and insights from
      various sub-disciplines of biology, including ecology, evolution, toxicology, and
      genetics. It also would benefit from a well-developed and broadly accepted model
      systems. The freshwater crustacean Daphnia is an excellent model organism for
      studying multiple stressors because it has been a chosen focus of study in all
      four of these fields. Daphnia is a widespread keystone species in most freshwater
      ecosystems, where it is routinely exposed to a multitude of anthropogenic and
      natural stressors. It has a fully sequenced genome, a well-understood life
      history and ecology, and a huge library of responses to toxicity. To make the
      case for its value as a model species, we consider the joint and separate effects
      of natural and three anthropogenic stressors-climatic change, calcium decline,
      and metal contaminants on daphniids. We propose that integrative approaches
      marrying various subfields of biology can advance our understanding of the
      combined effects of stressors. Such approaches can involve the measuring of
      multiple responses at several levels of biological organization from molecules to
      natural populations. For example, novel interdisciplinary approaches such as
      transcriptome profiling and mutation accumulation experiments can offer insights
      into how multiple stressors influence gene transcription and mutation rates
      across genomes, and, thus, help determine the causal mechanism between
      environmental stressors and population/community effects as well as long-term
      evolutionary patterns.

PMID- 21873645
TI  - ppiTrim: constructing non-redundant and up-to-date interactomes.
AB  - Robust advances in interactome analysis demand comprehensive, non-redundant and
      consistently annotated data sets. By non-redundant, we mean that the accounting
      of evidence for every interaction should be faithful: each independent
      experimental support is counted exactly once, no more, no less. While many
      interactions are shared among public repositories, none of them contains the
      complete known interactome for any model organism. In addition, the annotations
      of the same experimental result by different repositories often disagree. This
      brings up the issue of which annotation to keep while consolidating evidences
      that are the same. The iRefIndex database, including interactions from most
      popular repositories with a standardized protein nomenclature, represents a
      significant advance in all aspects, especially in comprehensiveness. However,
      iRefIndex aims to maintain all information/annotation from original sources and
      requires users to perform additional processing to fully achieve the
      aforementioned goals. Another issue has to do with protein complexes. Some
      databases represent experimentally observed complexes as interactions with more
      than two participants, while others expand them into binary interactions using
      spoke or matrix model. To avoid untested interaction information buildup, it is
      preferable to replace the expanded protein complexes, either from spoke or matrix
      models, with a flat list of complex members. To address these issues and to
      achieve our goals, we have developed ppiTrim, a script that processes iRefIndex
      to produce non-redundant, consistently annotated data sets of physical
      interactions. Our script proceeds in three stages: mapping all interactants to
      gene identifiers and removing all undesired raw interactions, deflating
      potentially expanded complexes, and reconciling for each interaction the
      annotation labels among different source databases. As an illustration, we have
      processed the three largest organismal data sets: yeast, human and fruitfly.
      While ppiTrim can resolve most apparent conflicts between different labelings, we
      also discovered some unresolvable disagreements mostly resulting from different
      annotation policies among repositories. Database URL:
      http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/ppiTrim.html.

PMID- 21873647
TI  - Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro
      hazard assessment of chemical carcinogenicity.
AB  - Hepatocyte-like cells derived from the differentiation of human embryonic stem
      cells (hES-Hep) have potential to provide a human relevant in vitro test system
      in which to evaluate the carcinogenic hazard of chemicals. In this study, we have
      investigated this potential using a panel of 15 chemicals classified as
      noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured
      whole-genome transcriptome responses with gene expression microarrays. We applied
      an ANOVA model that identified 592 genes highly discriminative for the panel of
      chemicals. Supervised classification with these genes achieved a cross-validation
      accuracy of > 95%. Moreover, the expression of the response genes in hES-Hep was
      strongly correlated with that in human primary hepatocytes cultured in vitro. In
      order to infer mechanistic information on the consequences of chemical exposure
      in hES-Hep, we developed a computational method that measures the responses of
      biochemical pathways to the panel of treatments and showed that these responses
      were discriminative for the three toxicity classes and linked to carcinogenesis
      through p53, mitogen-activated protein kinases, and apoptosis pathway modules. It
      could further be shown that the discrimination of toxicity classes was improved
      when analyzing the microarray data at the pathway level. In summary, our results
      demonstrate, for the first time, the potential of human embryonic stem cell-
      derived hepatic cells as an in vitro model for hazard assessment of chemical
      carcinogenesis, although it should be noted that more compounds are needed to
      test the robustness of the assay.

PMID- 21873648
TI  - SO(2)-induced neurotoxicity is mediated by cyclooxygenases-2-derived
      prostaglandin E(2) and its downstream signaling pathway in rat hippocampal
      neurons.
AB  - Sulfur dioxide (SO(2)) pollution in atmospheric environment is involved in
      neurotoxicity and increased risk for hospitalization and mortality of many brain
      disorders; however, our understanding of the mechanisms by which SO(2) caused
      harmful insults on neurons remains elusive. Here, we show that SO(2) exposure
      produced a neuronal insult, and the neurotoxic effect was likely via stimulating
      cyclooxygenase-2 (COX-2) elevation by activation of nuclear factor-kappaB (NF
      kappaB) activity and its acting on the promoter-distal NF-kappaB-binding site of
      COX-2 promoter. The action of SO(2) on elevating COX-2 ultimately appeared to be
      dependent on the increased production of arachidonic acid-derived prostaglandins,
      mainly prostaglandin E(2) (PGE(2)), and functioning of its EP2/4 receptors. Also,
      the molecular modulating process might be triggered by free radical attack from
      SO(2) metabolism in vivo and followed by activating cyclic adenosine
      monophosphate/protein kinase A pathway and enhancing probability of the release
      of glutamate, upregulating N-methyl-D-aspartic acid receptor expression and
      causing neuronal apoptosis. Our results reveal a mechanistic basis for exploring
      an association between SO(2) inhalation and increased risk for neurological
      disorders and opening up therapeutic approaches of treating, ameliorating, or
      preventing brain injuries resulting from SO(2) exposure in atmospheric polluting
      environment.

PMID- 21873646
TI  - Long-term exposure to ambient fine particulate pollution induces insulin
      resistance and mitochondrial alteration in adipose tissue.
AB  - We have previously shown that chronic exposure to ambient fine particulate matter
      (less than 2.5 MUm in aerodynamic diameter, PM2.5) pollution in conjunction with
      high-fat diet induces insulin resistance through alterations in inflammatory
      pathways. In this study, we evaluated the effects of PM2.5 exposure over a
      substantive duration of a rodent's lifespan and focused on the impact of long
      term exposure on adipose structure and function. C57BL/6 mice were exposed to
      PM2.5 or filtered air (FA) (6 h/day, 5 days/week) for duration of 10 months in
      Columbus, OH. At the end of the exposure, PM2.5-exposed mice demonstrated insulin
      resistance (IR) and a decrease in glucose tolerance compared with the FA-exposed
      group. Although there were no significant differences in circulating cytokines
      between PM2.5- and FA-exposed groups, circulating adiponectin and leptin were
      significantly decreased in PM2.5-exposed group. PM2.5 exposure also led to
      inflammatory response and oxidative stress as evidenced by increase of Nrf2
      regulated antioxidant genes. Additionally, PM2.5 exposure decreased mitochondrial
      count in visceral adipose and mitochondrial size in interscapular adipose depots,
      which were associated with reduction of uncoupling protein 1 (UCP1) expression
      and downregulation of brown adipocyte-specific gene profiles. These findings
      suggest that long-term ambient PM2.5 exposure induces impaired glucose tolerance,
      IR, inflammation, and mitochondrial alteration, and thus, it is a risk factor for
      the development of type 2 diabetes.

PMID- 21873649
TI  - Improving STI counselling services of non-formal providers in Bangladesh: testing
      an alternative strategy.
AB  - OBJECTIVE: The authors conducted this study to assess the effectiveness of using
      a public health detailing approach by medical representatives of a private
      pharmaceutical company to disseminate sexually transmitted infection (STI)
      counselling information to non-formal providers (NFPs) to improve their STI
      counselling services. METHODS: An intervention was developed that included
      developing STI counselling guidelines and training medical representatives to
      disseminate the counselling guidelines to NFPs. To assess the effectiveness of
      this intervention, the authors conducted 67 mystery client visits to compare the
      counselling provided by NFPs in intervention areas with counselling provided in
      areas where the intervention was not implemented. RESULTS: A significantly higher
      proportion (p<0.05) of mystery clients in the intervention area received advice
      that was consistent with the national STI counselling guidelines compared with
      the mystery clients in the control area. No mystery clients in the control area
      were told to use condoms while the STI lasts compared with 44% (95% CI 28% to
      62%) in the intervention area. Likewise, more than twice as many clients in the
      intervention area were advised not to visit sex workers (53% vs 23%; p=0.014).
      CONCLUSION: Public health detailing of medical representatives is a feasible
      mechanism to improve STI counselling services of NFPs in Bangladesh. Private
      sector companies provide a potential avenue for reaching the vast number of NFPs
      with basic information that they can share with their clients. The immediate
      improvements seen in this study suggest the strong potential of public health
      detailing as a training tool for NFPs.

PMID- 21873650
TI  - Solitary fibrous tumour of the pleura causing bulging of the thoracic wall in a
      44-year-old man.

PMID- 21873651
TI  - The clinician's response to a report of an incidental pulmonary embolism detected
      on multidetector CT.
AB  - BACKGROUND: The prevalence of incidental pulmonary emboli (PE) detected on
      contrast enhanced CT performed for other reasons is approximately 2.5%. The
      treatment decisions based upon the discovery of incidental PE have been less well
      reported. The purpose of this study was to report the clinician's response to,
      and consequences of, the finding of incidental PE on contrast enhanced CT.
      METHODS: Retrospective cohort study. Patients with incidental PE detected on a
      contrast enhanced CT were retrospectively identified at a single institution
      between 1 January 2009 and 31 December 2009. Case note review was performed to
      assess clinicians' responses to this finding. Patients with synchronous venous
      thromboembolism, unrecognised symptoms or factors preventing response assessment
      were excluded from this analysis. Patient and PE characteristics, treatment, and
      outcomes related to treatment and non-treatment were recorded. RESULTS: There
      were 73 patients with incidental PE: 52 were in the proximal pulmonary arteries
      and 21 were distal. 16 patients were excluded from the treatment analysis. 52 of
      57 (91.2%) patients were treated with therapeutic anticoagulation. There were 2
      (3.8%) serious adverse events related to treatment. 5 (8.8%) patients were not
      treated; 2 (40%) developed recurrent venous thromboembolism. Treatment of
      incidental PE was not significantly associated with patient age, PE risk factors
      or PE location. A smaller proportion of single incidental PE were treated than
      multiple incidental PE (p=0.047). CONCLUSION: There is morbidity associated with
      both treatment and non-treatment of incidental PE. However, despite the
      uncertainty about the natural history and clinical significance of incidental PE,
      the majority of patients at the authors' institution received prompt
      anticoagulation.

PMID- 21873654
TI  - Effects of gelatin hydrogel containing chymase inhibitor on scarring in a canine
      filtration surgery model.
AB  - PURPOSE: To investigate the effects of gelatin hydrogel (GH) containing a chymase
      inhibitor (CI) on intraocular pressure (IOP) and conjunctival scarring in a
      canine model of glaucoma surgery. METHODS: Glaucoma surgery models were made in
      beagles. As the first experiment, GH was implanted. IOP was measured for 4 weeks,
      followed by histologic evaluation. As the second experiment, GH containing a CI
      or GH alone was implanted. IOP and bleb features were evaluated for 12 weeks. The
      densities of proliferative cell nuclear antigen (PCNA)-positive cells,
      fibroblasts, and mast cells were quantified. The mRNA levels of transforming
      growth factor-beta (TGF-beta) and chymase were determined by real-time PCR.
      RESULTS: In the first experiment, IOP was significantly lower in the eyes treated
      with GH than that in the control eyes. The conjunctival area normalized by the
      scleral area was reduced in the treated eyes. In the second experiment, IOP
      reduction was maintained for 12 weeks in the eyes treated with GH containing a
      CI, but not in the eyes treated with GH alone. In addition, the bleb score was
      larger, whereas the adhesion score and densities of PCNA-positive cells,
      fibroblasts, mast cells, and chymase-positive cells were lower in the eyes
      treated with GH containing a CI. The mRNA levels of TGF-beta and chymase were
      significantly decreased in the eyes treated with GH containing a CI. CONCLUSIONS:
      Implanting GH alone maintained IOP reduction, whereas GH containing a CI enhanced
      the IOP-reducing effect by suppressing cell proliferation. This drug delivery
      system might be useful for maintaining filtering blebs for a longer duration
      after glaucoma surgery.

PMID- 21873652
TI  - Human 1-acylglycerol-3-phosphate O-acyltransferase isoforms 1 and 2: biochemical
      characterization and inability to rescue hepatic steatosis in Agpat2(-/-) gene
      lipodystrophic mice.
AB  - Loss-of-function mutations in 1-acylglycerol-3-phosphate O-acyltransferase
      (AGPAT) 2 in humans and mice result in loss of both the white and brown adipose
      tissues from birth. AGPAT2 generates precursors for the synthesis of
      glycerophospholipids and triacylglycerols. Loss of adipose tissue, or
      lipodystrophy, results in hyperinsulinemia, diabetes mellitus, and severe hepatic
      steatosis. Here, we analyzed biochemical properties of human AGPAT2 and its close
      homolog, AGPAT1, and we studied their role in liver by transducing their
      expression via recombinant adenoviruses in Agpat2(-/-) mice. The in vitro
      substrate specificities of AGPAT1 and AGPAT2 are quite similar for
      lysophosphatidic acid and acyl-CoA. Protein homology modeling of both the AGPATs
      with glycerol-3-phosphate acyltransferase 1 (GPAT1) revealed that they have
      similar tertiary protein structure, which is consistent with their similar
      substrate specificities. When co-expressed, both isoforms co-localize to the
      endoplasmic reticulum. Despite such similarities, restoring AGPAT activity in
      liver by overexpression of either AGPAT1 or AGPAT2 in Agpat2(-/-) mice failed to
      ameliorate the hepatic steatosis. From these studies, we suggest that the role of
      AGPAT1 or AGPAT2 in liver lipogenesis is minimal and that accumulation of liver
      fat is primarily a consequence of insulin resistance and loss of adipose tissue
      in Agpat2(-/-) mice.

PMID- 21873653
TI  - Inhibition of lens photodamage by UV-absorbing contact lenses.
AB  - PURPOSE: To determine whether class 1 UV-blocking contact lenses protect against
      UVB radiation-induced damage in a human lens epithelial cell line (HLE B-3) and
      postmortem human lenses using a proteomics approach. METHODS: HLE B-3 cells were
      exposed to 6.4 mW/cm(2) UVB radiation at 302 nm for 2 minutes (768 mJ/cm(2)) with
      or without covering by senofilcon A class 1 UV-blocking contact lenses or
      lotrafilcon A non-UV-blocking (lotrafilcon A has some UV-blocking ability, albeit
      minimal) contact lenses. Control cells were not exposed to UVB radiation. Four
      hours after treatment, cells were analyzed by two-dimensional difference gel
      electrophoresis and tandem mass spectrometry, and changes in protein abundance
      were quantified. F-actin and microtubule cytoskeletons were examined by
      fluorescence staining. In addition, human donor lenses were exposed to UVB
      radiation at 302 nm for 4 minutes (1536 mJ/cm(2)). Cortical and epithelial cell
      proteins were scraped from lens surfaces and subjected to the same protein
      analyses. RESULTS: Senofilcon A lenses were beneficial for protecting HLE B-3
      cells against UVB radiation-induced changes in caldesmon 1 isoform, lamin A/C
      transcript variant 1, DEAD (Asp-Glu-Ala-Asp) box polypeptide, beta-actin,
      glyceraldehyde 3-phosphate dehydrogenase (G3PDH), annexin A2, triose phosphate
      isomerase, and ubiquitin B precursor. These contact lenses also prevented actin
      and microtubule cytoskeleton changes typically induced by UVB radiation.
      Conversely, non-UV-blocking contact lenses were not protective. UVB-irradiated
      human lenses showed marked reductions in alphaA-crystallin, alphaB-crystallin,
      aldehyde dehydrogenase 1, betaS-crystallin, betaB2-crystallin, and G3PDH, and UV
      absorbing contact lenses significantly prevented these alterations. CONCLUSIONS:
      Senofilcon A class 1 UV-blocking contact lenses largely prevented UVB-induced
      changes in protein abundance in lens epithelial cells and in human lenses.

PMID- 21873655
TI  - In vivo cross-sectional observation and thickness measurement of bulbar
      conjunctiva using optical coherence tomography.
AB  - PURPOSE: To observe in vivo bulbar conjunctival structures, and determine the
      reproducibility of thickness measurements of normal human conjunctiva through
      optical coherence tomography (OCT) images. METHODS: The bulbar conjunctivas of
      three study groups were observed: five enucleated porcine eyes with 20 um
      thickness aluminum foils inserted beneath conjunctival stroma; five glaucoma
      patients with 6-0 thread placed beneath conjunctival stroma during
      trabeculectomy; and 18 normal subjects. The cross-sectional conjunctival images
      were acquired using the scanning protocol from an optical coherence tomography
      device (Anterior Segment 5 Line Raster scanning protocol, Cirrus HD-OCT; Carl
      Zeiss Meditec, Inc., Dublin, CA). The thickness of different conjunctival layers
      was measured using central corneal thickness measurement software in the 18
      normal subjects. Two reproducible parameters-interobserver (within-subject
      between-examiners) and intraobserver (within-subject between-date)-were estimated
      with intraclass correlation coefficients (ICC). RESULTS: A thin hyporeflective
      surface layer, corresponding to the conjunctival epithelium layer, was observed.
      Beneath it, the conjunctival stroma appeared hyperreflective and was separated by
      a demarcation from the underlying progressively lower reflective Tenon's capsule.
      The anatomic location of the demarcation, which represents the loose connection
      between the conjunctival stroma and Tenon's capsule, was confirmed by inserting
      aluminum foil in porcine eyes, and by a 6-0 thread mark in glaucoma patients'
      eyes. The average conjunctival epithelium, stroma, and full thickness of the 18
      normal subjects was 47.3 +/- 8.4 um, 190.8 +/- 47.5 um, and 238.8 +/- 51.1 um,
      respectively. The intraobserver and interobserver intraclass correlation
      coefficients ranged from 0.918 to 0.985. CONCLUSIONS: It is possible to
      accurately image and measure the cross-sectional structures of the bulbar
      conjunctival tissue with high resolution OCT.

PMID- 21873656
TI  - The KORA Eye Study: a population-based study on eye diseases in Southern Germany
      (KORA F4).
AB  - PURPOSE: The population-based KORA (Cooperative Health Research in the Region of
      Augsburg [Germany]) study was used to evaluate the prevalence of eye diseases and
      potential interactions with general health status, laboratory data, medication,
      and genetic background. METHODS: In all, 2593 probands, ranging in age from 32 to
      71 years (mean: 52 years), were asked in a standardized interview for the
      presence of cataracts, glaucoma, and corneal or retinal disorders; positive
      answers were validated and specified by treating ophthalmologists. Additional
      data came from a questionnaire or from laboratory data. RESULTS: We validated 10
      probands with corneal diseases (validation rate: 32%), 26 with retinal diseases
      (validation rate: 60%), 40 with glaucoma (validation rate: 75%), and 100
      participants with cataracts (validation rate: 88%). Glaucoma was significantly
      associated with increasing age, diabetes and its treatment, and the use of drugs
      in airway diseases. Cataracts were significantly associated with increasing age,
      female sex, hypertension, and diabetes. In females, cataracts were particularly
      associated with the use of ophthalmological corticosteroids, some
      antihypertensives, and antidiabetics. In contrast, cataracts in males were
      associated only with the use of angiotensin-converting enzyme inhibitors. We also
      tested some polymorphic markers; two (GJA8, CRYBB3) were significantly associated
      with cataracts. CONCLUSIONS: Self-reported ocular diagnoses by questionnaire
      showed varying degrees of accuracy; this method of data collection is valid,
      providing confirmation is obtained from treating ophthalmologists. It revealed a
      similar profile of major risk factors for cataracts (age, female sex, and
      diabetes) in Germany like that of other international studies. The reported
      associations between medical treatment and genetic polymorphisms in early-onset
      cataract merit further functional study.

PMID- 21873657
TI  - Comparing methods to estimate the human lens power.
AB  - PURPOSE. To compare the accuracy of different methods of calculating human lens
      power when lens thickness is not available. METHODS. Lens power was calculated by
      four METHODS: Three methods were used with previously published biometry and
      refraction data of 184 emmetropic and myopic eyes of 184 subjects (age range, 18
      63 years; spherical equivalent range, -12.38 to +0.75 D). These three methods
      consist of the Bennett method, which uses lens thickness, a modification of the
      Stenstrom method and the Bennett-Rabbetts method, both of which do not require
      knowledge of lens thickness. These methods include c constants, which represent
      distances from lens surfaces to principal planes. Lens powers calculated with
      these methods were compared with those calculated using phakometry data available
      for a subgroup of 66 emmetropic eyes (66 subjects). RESULTS. Lens powers obtained
      from the Bennett method corresponded well with those obtained by phakometry for
      emmetropic eyes, although individual differences up to 3.5 D occurred. Lens
      powers obtained from the modified-Stenstrom and Bennett-Rabbetts methods deviated
      significantly from those obtained with either the Bennett method or phakometry.
      Customizing the c constants improved this agreement, but applying these constants
      to the entire group gave mean lens power differences of 0.71 +/- 0.56 D compared
      with the Bennett method: By further optimizing the c constants, the agreement
      with the Bennett method was within +/-1 D for 95% of the eyes. CONCLUSIONS. With
      appropriate constants, the modified Stenstrom and Bennett-Rabbetts methods
      provide a good approximation of the Bennett lens power in emmetropic and myopic
      eyes.

PMID- 21873658
TI  - Profile and predictors of normal ganglion cell-inner plexiform layer thickness
      measured with frequency-domain optical coherence tomography.
AB  - PURPOSE: To describe the profile and identify the predictors of the ganglion cell
      inner plexiform layer (GCIPL) thickness measured with frequency-domain optical
      coherence tomography (FD-OCT) in normal eyes. METHODS: Two hundred eighty-two
      normal subjects underwent macular and optic disc scanning in both eyes with
      Cirrus high-definition (HD)-OCT (Carl Zeiss Meditec, Dublin, CA). Linear
      regression analyses were performed to determine the association between GCIPL
      thickness and age, sex, ethnicity (Europeans, Africans, Hispanics, Asians, and
      Indians), eye laterality, refraction, intraocular pressure, axial length, central
      corneal thickness, mean retinal nerve fiber layer (RNFL) thickness, disc and rim
      areas, cup-to-disc area, vertical and horizontal cup-to-disc diameter ratios,
      vertical rim thickness, and OCT signal strength. RESULTS: The mean (+/-SD) age
      was 46.2 +/- 16.9 years (range, 18-84 years). The mean and minimum GCIPL
      thicknesses (+/-SD) were 82.1 +/- 6.2 and 80.4 +/- 6.4 MUm, respectively. There
      were significant differences in GCIPL thickness between macular sectors (P <
      0.05), except between the superotemporal and inferonasal sectors (P = 0.63). The
      superonasal sector had the thickest and the inferior had the thinnest GCIPL. The
      GCIPL of the superior hemisphere was thicker than that of the inferior, and the
      nasal sector GCIPL was significantly thicker than the temporal one (P < 0.001).
      The average GCIPL did not differ between male and female subjects (P = 0.16)
      after adjustment for axial length and between ethnic groups (P = 0.41) after
      adjustment for age, axial length, and RNFL thickness. Significant predictors of
      mean GCIPL thickness were average RNFL thickness (beta = 0.37, P < 0.001), age
      (beta = -0.083, P < 0.001), axial length (beta = -0.87, P = 0.001), and male sex
      (beta = -1.62, P = 0.005). CONCLUSIONS: The independent factors associated with
      thinner GCIPL include thinner RNFL, older age, longer ocular axial length, and
      being male. Although the magnitude of the effect of age, axial length, and sex
      are small, these factors should be taken into account when interpreting Cirrus HD
      OCT-based GCIPL thickness measurements.

PMID- 21873660
TI  - Literacy is an independent risk factor for vision impairment and poor visual
      functioning.
AB  - PURPOSE: People with limited literacy are at increased risks of chronic systemic
      conditions. The authors therefore investigated the independent contribution of
      limited literacy on visual impairment and visual function in a large eye survey
      in Singapore. METHODS: The authors undertook a population-based, cross-sectional
      study of Asian Malays (>= 40 years old). Visual impairment was defined as logMAR
      (logarithm of minimal angle of resolution) visual acuity > 0.30 in the better
      seeing eye. Information regarding reading and writing literacy levels and other
      independent variables, including sociodemographic measures (e.g., education,
      income), were obtained from a standardized interview. Visual functioning was
      assessed using a modified and validated version of the Vision-Specific
      Functioning Scale using Rasch analysis. RESULTS: Of the 3280 participants, 553
      (16.9%) had inadequate reading literacy and 688 (21.0%) had inadequate writing
      literacy. In multivariate analysis, persons with inadequate reading literacy were
      more likely to have presenting visual impairment (odds ratio [OR] = 2.66; 95%
      confidence interval [CI] = 1.91 to 3.72; P < 0.001), best-corrected visual
      impairment (OR = 2.59; 95% CI = 1.70 to 3.96; P < 0.001), and poorer visual
      functioning (beta coefficient = 0.58; 95% CI = 1.57 to 3.02; P < 0.001), even
      controlling for education, income, and other patients' characteristics. Similar
      associations were found for inadequate writing literacy. CONCLUSIONS: Inadequate
      literacy is independently associated with visual impairment and poorer visual
      functioning. Interventions that address literacy may help to reduce socioeconomic
      disparities in visual impairment.

PMID- 21873661
TI  - A population-based assessment of 24-hour intraocular pressure among subjects with
      primary open-angle glaucoma: the handan eye study.
AB  - PURPOSE: To describe the distribution of the 24-hour intraocular pressure (IOP)
      among subjects with primary open-angle glaucoma (POAG) in a population-based
      study in north China. METHODS: All untreated POAG patients (n = 66) identified in
      the Handan Eye Study were invited to attend a follow-up study in which IOP was
      tested with a Goldmann applanation tonometer at 10 AM, 2 PM, 6 PM, 10 PM, 2 AM,
      and 6 AM. RESULTS: Forty-seven subjects with untreated POAG (47/66; 71.2%)
      attended the study. Of them, 39 (83.0%) had a peak IOP <= 21 mm Hg. The peak IOP
      (mean +/- SD) was 18.4 +/- 3.7 mm Hg. Peak IOP occurred in early morning in
      approximately 76.5% of the subjects (6 AM to 10 AM), and the trough occurred
      during night time in 70.2% of the subjects (10 PM to 2 AM). The 24-hour IOP (mean
      +/- SD) was 15.4 +/- 3.1 mm Hg and the mean fluctuation was 6.0 +/- 2.2 mm Hg
      (range, 2-11 mm Hg). In the 22 persons with unilateral glaucoma, no significant
      differences were found in mean 24-hour IOP, peak IOP, trough IOP, or IOP
      fluctuation when comparing the glaucomatous eye with the nonglaucomatous eye (P >
      0.05). CONCLUSIONS: About 80% of Chinese persons with POAG identified in a
      population-based study had maximum IOPs of 21 mm Hg or less over a 24-hour
      period. Twenty-four-hour IOP was similar between glaucomatous and contralateral
      nonglaucomatous eyes suggesting that factors other than IOP may play a role in
      the development of glaucomatous optic neuropathy in these eyes.

PMID- 21873663
TI  - Integrin beta1 is necessary for the maintenance of corneal structural integrity.
AB  - PURPOSE: The precise role of a normal keratocyte in maintaining corneal
      structural integrity is unclear; it is generally considered to remain quiescent
      at the end of cell division. Given that integrins are essential for
      cell/extracellular matrix interactions, the authors tested the hypothesis that
      integrin expression by keratocytes is essential for corneal structure and
      function. METHODS: Using a tamoxifen-dependent cre recombinase expressed under
      the control of a fibroblast-specific promoter/enhancer, the authors conditionally
      deleted the integrin beta1 (Itgb1) gene in mouse keratocytes during the postnatal
      matrix maturation phase of the cornea. The effects of this deletion were
      monitored histologically and by macroscopic observation of the cornea. RESULTS:
      The resultant cornea shows an initial thinning of the stroma, reduced space
      between collagen fibrils, loss of epithelial layers and subsequent edema,
      thickening of Descemet's membrane, and degenerative changes in the endothelial
      cell layer, with eventual scarring. These pathologic changes have some
      similarities to human corneal disease keratoconus. The phenotype did not develop
      when Itgb1 was deleted after complete corneal maturation. CONCLUSIONS: Loss of
      integrin beta1 expression in keratocytes during the phase of stromal maturation
      results in corneal thinning and edema. Keratocyte-ECM interaction is essential
      for matrix maturation and thus in the maintenance of corneal structural
      integrity. This model has relevance in understanding corneal diseases such as
      keratoconus.

PMID- 21873662
TI  - Retinal disease course in Usher syndrome 1B due to MYO7A mutations.
AB  - PURPOSE. To determine the disease course in Usher syndrome type IB (USH1B) caused
      by myosin 7A (MYO7A) gene mutations. METHODS. USH1B patients (n = 33, ages 2-61)
      representing 25 different families were studied by ocular examination, kinetic
      and chromatic static perimetry, dark adaptometry, and optical coherence
      tomography (OCT). Consequences of the mutant alleles were predicted. RESULTS. All
      MYO7A patients had severely abnormal ERGs, but kinetic fields revealed regional
      patterns of visual loss that suggested a disease sequence. Rod-mediated vision
      could be lost to different degrees in the first decades of life. Cone vision
      followed a more predictable and slower decline. Central vision ranged from normal
      to reduced in the first four decades of life and thereafter was severely
      abnormal. Dark adaptation kinetics was normal. Photoreceptor layer thickness in a
      wide region of central retina could differ dramatically between patients of
      comparable ages; and there were examples of severe losses in childhood as well as
      relative preservation in patients in the third decade of life. Comparisons were
      made between the mutant alleles in mild versus more severe phenotypes.
      CONCLUSIONS. A disease sequence in USH1B leads from generally full but impaired
      visual fields to residual small central islands. At most disease stages, there
      was preserved temporal peripheral field, a potential target for early phase
      clinical trials of gene therapy. From data comparing patients' rod disease in
      this cohort, the authors speculate that null MYO7A alleles could be associated
      with milder dysfunction and fewer photoreceptor structural losses at ages when
      other genotypes show more severe phenotypes.

PMID- 21873664
TI  - Numerical modeling of paintball impact ocular trauma: identification of
      progressive injury mechanisms.
AB  - PURPOSE: To create a computer-based numerical simulation model for comparison
      with empiric paintball-ocular ballistic study findings, allowing identification
      of the dynamic physical mechanisms (stress, strain, pressure) responsible for
      intraocular traumatic injury accompanying blunt ocular impact. Virtual
      experiments with numerical models could exploit mathematical "instrumentation" to
      facilitate internal observation impossible with physical experiments alone.
      METHODS: Models of human eye structures and orbit were implemented into the
      finite-volume Eulerian numerical hydrocode CTH. Numerical simulation results were
      compared with dynamic imaging and postimpact histopathology obtained during
      previous ballistic impact experiments on fresh porcine eyes impacted with
      paintballs. Forty numerical simulations and 59 impact experiments were conducted
      as part of the study. RESULTS: Time-lapse correlations showed the CTH models to
      be dynamically commensurate with orbital penetration and globe deformation
      measured from ballistic high-speed videos. CTH also predicted the types and
      levels of damage observed in detailed postimpact pathologic assessments of
      porcine specimens. High strain in the ciliary body and zonule corresponded with
      angle recession and lens displacement pathologically. Globe rupture was attained
      at the highest paintball impact velocities in both the porcine ballistic studies
      and CTH models, consistent with predicted dynamic intraocular pressures. The
      simulations also revealed that phenomena such as macular Berlin's edema,
      midperipheral retinoschisis, and choroidal and retinal detachment might be
      explained by focal dynamic pressure-wave reflection from the interior surface of
      the globe. CONCLUSIONS: Significant insight was gained regarding the physical
      mechanisms responsible for injury. CTH predictions corresponded closely with
      previous ballistic experimental results, adding intraocular detail otherwise
      unattainable.

PMID- 21873659
TI  - Candidate gene association study for diabetic retinopathy in persons with type 2
      diabetes: the Candidate gene Association Resource (CARe).
AB  - PURPOSE: To investigate whether variants in cardiovascular candidate genes, some
      of which have been previously associated with type 2 diabetes (T2D), diabetic
      retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the
      Candidate gene Association Resource (CARe). METHODS: Persons with T2D who were
      enrolled in the study (n = 2691) had fundus photography and genotyping of single
      nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions
      were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades >=
      14 and >= 30. The chi2 analyses for each CARe cohort were combined by Cochran
      Mantel-Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple
      hypothesis testing. Logistic regression was performed with adjustment for other
      DR risk factors. Results from replication in independent cohorts were analyzed
      with CMH meta-analysis methods. RESULTS: Among 39 genes previously associated
      with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The
      strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni
      correction). These associations remained significant after adjustment for DR risk
      factors. Among other genes examined, several variants were associated with DR
      with significant P values, including rs6856425 tagging alpha-l-iduronidase (IDUA)
      (P = 2.1 * 10(-5), after Bonferroni correction). However, replication in
      independent cohorts did not reveal study-wide significant effects. The P values
      after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.
      CONCLUSIONS: Genes associated with DN, T2D, and vascular diseases do not appear
      to be consistently associated with DR. A few genetic variants associated with DR,
      particularly those in SELP and near IDUA, should be investigated in additional DR
      cohorts.

PMID- 21873666
TI  - Mathematical projection model of visual loss due to fuchs corneal dystrophy.
AB  - PURPOSE. To devise a mathematical disease classification model for eyes with
      primary guttata cornea, on the bases of endothelial loss trajectory and
      probability of advanced disease. METHODS. A series of 1971 patients (3281 eyes),
      some with and some without guttata corneas, undergoing specular microscopy were
      retrospectively reviewed. The eyes were classified into four stages; stage 0,
      without guttae; 1, guttata cornea without edema; 2, mild Fuchs' corneal dystrophy
      (FCD); and 3, severe FCD, according to clinical records, and patient age and
      corneal endothelial cell density (ECD) were plotted. Nonparametric density
      smoothing was used to create a contour map, and a best-fit curve for ECD loss was
      calculated. The relation between ECD decrease rate and the stages were evaluated.
      RESULTS. Endothelial decrease rate in stage 0 was 0.44%/year, which was
      compatible with that of normal eyes reported in previous studies. Decrease rates
      of stages 1, 2, and 3 were 0.81%, 2.65%, and 3.08%/ year, respectively. The age
      ECD loss curves of 1.40%/year (ECO(1.4)) and 2.00%/year (ECO(2.0)) further
      divided stage 1 into three subgroups; stage 1a, asymptomatic guttata cornea; 1b,
      borderline guttata cornea; and 1c, pre-FCD. The ECO(2.0) cutoff line
      differentiated eyes with FCD from those without edema with a sensitivity and
      specificity of >90%. Stage 1c eyes were below ECO(2.0) and had a decrease rate as
      high as FCD. CONCLUSIONS. This mathematical model can be used to predict the
      prognosis of patients with primary guttata cornea.

PMID- 21873665
TI  - PITX2 is involved in stress response in cultured human trabecular meshwork cells
      through regulation of SLC13A3.
AB  - PURPOSE: Mutations of the PITX2 gene cause Axenfeld-Rieger syndrome (ARS) and
      glaucoma. In this study, the authors investigated genes directly regulated by the
      PITX2 transcription factor to gain insight into the mechanisms underlying these
      disorders. METHODS: RNA from nonpigmented ciliary epithelium cells transfected
      with hormone-inducible PITX2 and activated by mifepristone was subjected to
      microarray analyses. Data were analyzed using dCHIP algorithms to detect
      significant differences in expression. Genes with significantly altered
      expression in multiple microarray experiments in the presence of activated PITX2
      were subjected to in silico and biochemical analyses to validate them as direct
      regulatory targets. One target gene was further characterized by studying the
      effect of its knockdown in a cell model of oxidative stress, and its expression
      in zebrafish embryos was analyzed by in situ hybridization. RESULTS: Solute
      carrier family 13 sodium-dependent dicarboxylate transporter member 3 (SLC13A3)
      was identified as 1 of 47 potential PITX2 target genes in ocular cells. PITX2
      directly regulates SLC13A3 expression, as demonstrated by luciferase reporter and
      chromatin immunoprecipitation assays. Reduction of PITX2 or SLC13A3 levels by
      small interfering RNA (siRNA)-mediated knockdown augmented the death of
      transformed human trabecular meshwork cells exposed to hydrogen peroxide.
      Zebrafish slc13a3 is expressed in anterior ocular regions in a pattern similar to
      that of pitx2. CONCLUSIONS: The results indicate that SLC13A3 is a direct
      downstream target of PITX2 transcriptional regulation and that levels of PITX2
      and SLC13A3 modulate responses to oxidative stress in ocular cells.

PMID- 21873667
TI  - In vivo gene expression profiling of retina postintravitreal injections of
      dexamethasone and triamcinolone at clinically relevant time points for patient
      care.
AB  - PURPOSE: To identify retinal genes and their relevant expression pathways
      affected by intravitreal injections of dexamethasone (Dex) and triamcinolone
      acetonide (TAA) in mice at clinically relevant time points for patient care.
      METHODS: Differential gene expressions of over 34,000 well-characterized mouse
      genes, in the retinas of 6-week-old C57BL/6J mice, were analyzed after
      intravitreal steroid injections at 1 week and 1 month time points, using mouse
      genome microarrays. The data were analyzed using commercial microarray analysis
      software for biologically relevant changes in gene expression pathways. RESULTS:
      A common gene pathway, with differentially activated genes for both steroids and
      time points, was "Semaphorin Signaling in Neurons," a member of the "Axonal
      Guidance Signaling System." At 1 week postinjection a common theme was activation
      of genes expressed in retinal glial cells, tumor necrosis factor-alpha, and
      transforming growth factor-beta signaling pathways and upregulation of stress
      response proteins (Serpina3n, Cebpd), as well as neuropeptide signaling
      somatostatin receptor (Sstr2). Unique for Dex was the upregulation of acute phase
      proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin signaling receptor,
      whereas EphrinB receptor ephexin 1 (Argef15) was downregulated. Folate signaling
      appears to be unique for TAA at 1 week (Folh1, Cubn), whereas aryl-hydrocarbon
      receptor signaling might be important for both steroids at 1 month postinjection.
      CONCLUSIONS: Understanding the molecular and genetic effects of intraocular
      steroid treatments is of clinical relevance. This in vivo study has elucidated
      several genes and pathways that are potentially altering the
      neuroprotective/neurodegenerative balance between glial and retinal ganglion
      cells during intravitreal steroid treatment.

PMID- 21873668
TI  - Effects of lutein supplementation on macular pigment optical density and visual
      acuity in patients with age-related macular degeneration.
AB  - PURPOSE: There is evidence from several large-scale clinical trials that reduced
      intake of lutein, a major component of the macular pigment, is a risk factor for
      the development of AMD. In the present study (LISA; Lutein Intervention Study
      Austria) it was hypothesized that lutein supplementation increases macular
      pigment optical density (MPOD). In addition, an investigation was conducted into
      whether lutein supplementation improves visual acuity (VA) and macular function
      (mean differential light threshold; MDLT), as assessed with microperimetry.
      METHODS: One hundred twenty-six patients with AMD (AREDS [Age-related Eye Disease
      Study] stages 2, 3, and 4) were included in this randomized (2:1), placebo
      controlled, double-masked parallel group study. Lutein or placebo was
      administered for 6 months. MPOD was measured with a custom-built reflectometer.
      VA was assessed with ETDRS (Early Treatment Diabetic Retinopathy Study) charts,
      and MDLT was assessed with a microperimeter. RESULTS: Lutein significantly
      increased MPOD by 27.9% +/- 2.9% (P < 0.001 versus placebo). No significant
      effect of lutein supplementation on MDLT or VA was seen, although a tendency
      toward an increase was seen for both parameters (MDLT, P = 0.096 versus placebo;
      VA, P = 0.070 versus placebo). A significant correlation was found, however,
      between the increase in MPOD after 6 months and the increase in MDLT after 6
      months (r = 0.25, P = 0.027), as well as between the increase in MPOD after 6
      months and the increase in VA after 6 months (r = 0.27, P = 0.013). CONCLUSIONS:
      The present study demonstrates that lutein supplementation increases MPOD, as
      assessed with an objective METHOD: The correlation between the change in MPOD and
      the change in VA and MDLT indicates that patients who show a pronounced increase
      in MPOD also benefit in terms of visual function. (ClinicalTrials.gov number,
      NCT00879671.).

PMID- 21873669
TI  - Semiautomated image processing method for identification and quantification of
      geographic atrophy in age-related macular degeneration.
AB  - PURPOSE: To determine intraobserver and interobserver longitudinal measurement
      variability of novel semiautomated software for quantification of age-related
      macular degeneration-associated geographic atrophy (GA) based on confocal
      scanning laser ophthalmoscopy fundus autofluorescence (FAF) imaging. METHODS:
      Three-field FAF (excitation 488 nm, emission 500-700 nm), near-infrared
      reflectance (820 nm), and blue reflectance (488 nm) images of 30 GA subjects were
      recorded according to a standardized protocol at baseline after 6 and 12 months.
      At all visits, the GA area was analyzed on central FAF images by seven
      independent readers using semiautomated software. The software allows direct
      export of FAF images from the database and semiautomated detection of atrophic
      areas by shadow correction, vessel detection, and selection of seed points.
      RESULTS: The mean size of atrophy at baseline and the mean progression rate were
      5.96 mm2 (range, 1.80-15.87) and 1.25 mm2/year (0.42-2.93), respectively. Mean
      difference of interobserver agreement (Bland-Altman statistics) ranged from -0.25
      to 0.30 mm2 for the baseline visit and from -0.14 to 0.11 mm2/year for the
      atrophy progression rate. Corresponding reflectance images were helpful for
      lesion boundary discrimination, particularly for evaluation of foveal GA
      involvement and when image quality was poor. CONCLUSIONS: The new image
      processing software offers an accurate, reproducible, and time-efficient
      identification and quantification of outer retinal atrophy and its progression
      over time. It facilitates measurements both in natural history studies and in
      interventional trials to evaluate new pharmacologic agents designed to limit GA
      enlargement.

PMID- 21873670
TI  - Enhancement of ON-bipolar cell responses of cone electroretinograms in rabbits
      with the Pro347Leu rhodopsin mutation.
AB  - PURPOSE: To determine how the different stages of retinal processing change after
      photoreceptor degeneration in rabbits carrying the Pro347Leu rhodopsin mutation
      (Tg rabbits). METHODS: Cone electroretinograms (ERGs) were elicited by 150-ms
      duration stimuli from 13 Tg rabbits at 12 and 24 weeks of age. The ERG recordings
      were made before and after an intravitreal injection of tetrodotoxin citrate
      (TTX) plus N-methyl-dl-aspartic acid (NMDA), with the addition of 2-amino-4
      phosphonobutyric acid (APB) and then cis-2,3-piperidine-dicarboxylic acid (PDA)
      or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Digital subtraction of the ERG
      after the injection from the ERG before the injection was used to extract the
      components that were blocked by these drugs. Thirteen age-matched, wild-type (WT)
      rabbits were studied with the same protocol. RESULTS: In Tg rabbits, the cone
      ERGs elicited by intermediate intensities had a depolarizing pattern. At 12 weeks
      of age, the photoreceptor and OFF-bipolar/horizontal cell responses reflected in
      the ERG in the Tg rabbits did not differ significantly from those in the WT
      rabbits. The ON-bipolar cells and the third-order neuronal responses recorded
      after pharmacologic blockade were significantly enhanced in the Tg rabbits
      compared with those recorded in the WT rabbits. At 24 weeks of age, the ERG
      waveforms representing the photoreceptors and OFF-bipolar/horizontal cell
      responses were significantly decreased, but those representing the ON-bipolar
      cell and third-order neuronal responses were still preserved in the Tg rabbits.
      CONCLUSIONS: A depolarizing pattern of the cone ERG responses was seen in
      Pro347Leu Tg rabbits. The enhancement or preservation of the ON-bipolar cell
      response in the ERGs contributed to shaping the waveform in the Tg rabbits. In
      this model, the functional alterations in the ON-pathway took place before the
      deterioration of cone photoreceptor function.

PMID- 21873672
TI  - Quantification of peripapillary sparing and macular involvement in Stargardt
      disease (STGD1).
AB  - PURPOSE: To quantify and compare structure and function across the macula and
      peripapillary area in Stargardt disease (STGD1). METHODS: Twenty-seven patients
      (27 eyes) and 12 age-similar controls (12 eyes) were studied. Patients were
      classified on the basis of full-field electroretinogram (ERG) results: Fundus
      autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT)
      horizontal line scans were obtained through the fovea and peripapillary area. The
      thicknesses of the outer nuclear layer plus outer plexiform layer (ONL+), outer
      segment (OS), and retinal pigment epithelium (RPE) were measured through the
      fovea, and peripapillary areas from 1 degrees  to 4 degrees  temporal to the
      optic disc edge using a computer-aided, manual segmentation technique. Visual
      sensitivities in the central 10 degrees  were assessed using microperimetry and
      related to retinal layer thicknesses. RESULTS: Compared to the central macula,
      the differences between controls and patients in ONL+, OS, and RPE layer
      thicknesses were less in the nasal and temporal macula. Relative sparing of the
      ONL+ and/or OS layers was detected in the nasal (i.e., peripapillary) macula in 8
      of 13 patients with extramacular disease on FAF; relative functional sparing was
      also detected in this subgroup. All 14 patients with disease confined to the
      central macula, as detected on FAF, showed ONL+ and OS layer thinning in regions
      of normal RPE thickness. CONCLUSIONS: Relative peripapillary sparing was detected
      in STGD1 patients with extramacular disease on FAF. Photoreceptor thinning may
      precede RPE degeneration in STGD1.

PMID- 21873671
TI  - Molecular chaperone function for myocilin.
AB  - PURPOSE: Myocilin is thought to be a stress response protein, but its exact
      molecular functions have not been established. Studies were conducted to see
      whether myocilin can act as a general molecular chaperone. METHODS: Myocilin was
      isolated and purified from porcine trabecular meshwork (TM) cell culture media.
      Its ability to protect citrate synthase, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), and the restriction endonuclease DrdI from thermal inactivation was
      evaluated. Light scattering was used to evaluate thermally induced aggregation of
      citrate synthase. Myocilin induction was assessed after exposure of TM cells to
      several types of stress treatments. RESULTS: Levels of extracellular myocilin
      expressed by TM cells were increased in response to mechanical stretch, heat
      shock, TNFalpha, or IL-1alpha. Myocilin protected citrate synthase activity
      against thermal inactivation for 5 minutes at 55 degrees C in a concentration
      dependent manner, with nearly full protection of 1.5 MUM citrate synthase in the
      presence of 650 nM myocilin. Myocilin significantly reduced thermal aggregation
      of citrate synthase to levels 36% to 44% of control levels. Myocilin also
      protected GAPDH from thermal inactivation for 10 minutes at 45 degrees C.
      Myocilin at 18 nM was more effective than 1 MUM bovine serum albumin at
      protecting DrdI from thermal inactivation. CONCLUSIONS: Myocilin is induced in
      response to several cellular stresses and displays general molecular chaperone
      activity by protecting DrdI, citrate synthase, and GAPDH from thermal
      inactivation. Myocilin also suppresses the thermal aggregation of citrate
      synthase. One function of myocilin may be to serve as a molecular chaperone.

PMID- 21873673
TI  - Change in peripheral refraction over time in Singapore Chinese children.
AB  - PURPOSE. Relative peripheral hyperopia has been associated with central myopia.
      This study was conducted to determine whether baseline relative peripheral
      hyperopia is associated with an increased risk of developing myopia or myopia
      progression in young Singapore Chinese children. METHODS. One hundred eighty
      seven children who participated in the Peripheral Refraction in Preschool
      Children (PREP) Study at baseline underwent a follow-up examination.
      Autorefraction was performed at five eccentricities with an infrared
      autorefractor after cycloplegia: central axis and 15 degrees  and 30 degrees 
      eccentricities in the nasal and temporal visual fields. The primary outcomes were
      development of myopia among children who were nonmyopic at baseline, and myopia
      progression in those who were myopic at baseline. RESULTS. The mean age of the
      children at baseline was 7.2 +/- 3.0 years, and the mean duration of follow-up
      was 1.26 years. At baseline, 96 children were myopic (mean central spherical
      equivalent [SE] -2.75 +/- 1.72 D) and 91 were nonmyopic (mean central SE 0.76 +/-
      0.81 D). Baseline relative peripheral hyperopia was not associated with a greater
      likelihood of becoming myopic or myopia progression. At follow-up, children who
      remained nonmyopic (n = 24) retained relative peripheral myopia at all
      eccentricities, whereas those who became myopic (n = 67) developed relative
      peripheral hyperopia at the nasal (+0.44 +/- 0.72 D) and temporal 30 degrees 
      (+0.13 +/- 0.74 D). The mean change in central SE was -1.51 +/- 0.63 D/y for
      children who developed myopia, -0.82 +/- 0.76 D/y for children who were myopic at
      baseline, and -1.05 +/- 0.80 D/y for all children. CONCLUSIONS. Baseline
      peripheral refraction did not predict the subsequent onset of myopia or influence
      the progression of myopia.

PMID- 21873674
TI  - Endothelin-1-induced proliferation is reduced and Ca2+ signaling is enhanced in
      endothelin B-deficient optic nerve head astrocytes.
AB  - PURPOSE: To characterize the influence of endothelin-1 (ET-1) on optic nerve head
      astrocyte (ONHA) proliferation and Ca2+ signaling in ONHAs lacking functional
      endothelin B (ETB) receptors. METHODS: ONHAs were isolated from adult wild type
      (WT) and transgenic spotting lethal (TSL) rats, lacking functional ETB receptors.
      ONHA specificity was confirmed by positive glial fibrillary acidic protein
      (GFAP), negative A2B5 (a marker for type II astrocytes located outside the optic
      nerve head) and myelin basic protein (MBP) labeling. The mitogenic effects of 10
      7 or 10-9 M ET-1, or vehicle were investigated for 48 or 72 hours in WT and TSL
      ONHAs. Intracellular calcium levels ([Ca2+](i)) were assessed in ONHAs loaded
      with fura-2 calcium indicator dye. RESULTS: ET-1-induced proliferation of TSL
      ONHAs was blunted at 48 hours (by 37% at 10-7 M and by 33% at 10-9 M) and 72
      hours (by 117% at 10-7 M and by 100% at 10-9 M) compared with WT cells. ET-1
      induced ONHA fura-2 ratio increases were significantly greater in TSL ONHAs (by
      20% at 10-7 M and by 48% at 10-9 M) compared with WT ONHAs. ET-1-induced fura-2
      ratio increases were blocked after pretreatment with BQ-610 (ETA antagonist) in
      WT and TSL ONHAs, but not by BQ-788 (ETB antagonist) in WT ONHAs. CONCLUSIONS: ET
      1-induced ONHA proliferation is reduced in cells lacking functional ETB
      receptors, ET-1-induced [Ca2+](i) increases are enhanced in the absence of
      functional ETB receptors, and ETA, but not ETB, is required for ET-1-induced
      [Ca2+](i) elevation.

PMID- 21873675
TI  - Cross-sectional sample of peripheral refraction in four meridians in myopes and
      emmetropes.
AB  - PURPOSE: The study of peripheral refractive error is of growing interest as
      degradation of the retinal image quality in the periphery is known to affect
      central refractive error development and ocular shape in animal models. The
      purpose of this study was to measure peripheral refraction across the horizontal,
      vertical, and two oblique meridians in a group of myopic and emmetropic adults
      and to investigate retinal asymmetry in the human retina. METHODS: Thirty-one
      myopes (spherical equivalent between -2.00 and -9.62 D) and 20 emmetropes
      (spherical equivalent between -0.50 and +0.50 D) with astigmatism less than -0.75
      D, participated in the project. Noncycloplegic peripheral refraction measurements
      were captured with an autorefractor (NVision K-5001; Shin-Nippon, Tokyo, Japan)
      at the fovea and up to 30 degrees  eccentricity in the horizontal, vertical, and
      two oblique meridians in 10 degrees  steps. RPR was calculated by subtracting the
      foveal spherical equivalent refraction from that obtained at each eccentric
      location. RESULTS: Along all measured meridians, myopic eyes showed a relative
      hyperopic shift in the periphery, with the superior-temporal portion of the
      retina exhibiting the smallest shift. Emmetropic eyes, however, exhibited a
      relatively consistent refractive profile across all meridians and eccentricities,
      confirming a spherical retinal shape for this group. In addition, off-axis
      astigmatism increased with eccentricity in all meridians. CONCLUSIONS: These
      results suggest that the myopic eye tends toward an ellipsoid shape, rather than
      the globular shape of an emmetropic eye.

PMID- 21873676
TI  - Target search and identification performance in low vision patients.
AB  - PURPOSE: To introduce a novel approach to topographic function assessment in
      visual impairment that requires neither fixation nor reading. METHODS: One
      hundred thirty-five consecutive low vision patients with varying diagnoses and 30
      control subjects of comparable median age participated. Performance was measured
      in a search task that required finding and identifying visual targets which
      appeared consecutively on a monitor in 32 locations of the central field of gaze.
      The task specifically discourages steady fixation and the subjects could make eye
      movements as needed to locate targets. Target size was always double the size
      threshold, and no manual action was required. The best attainable reading speed
      at any size was routinely measured (MNread). Main outcome measure was response
      latency necessary to solve the task. Data were median latencies and sums of all
      latencies. RESULTS: Measurements yielded a wide variety of performance levels,
      with a factor of 14 to 16 between best and worst performers. The highest
      correlation existed between median response latency in the search task and best
      attainable reading speed. Only a weak correlation was found between performance
      and visual acuity. No statistically significant correlations were found with age
      or diagnosis. CONCLUSIONS: The "search-and-identify" paradigm and continuous text
      reading share an important mechanism that determines performance in both tasks.
      The authors hypothesize that the factor enabling patients to perform well in both
      paradigms is oculomotor skill and/or eye movement strategy. Results show that the
      search test is a useful tool for the easy assessment of impaired vision
      independent of language, level of literacy, and reading habits.

PMID- 21873677
TI  - Repair of strabismus and binocular fusion in children with cerebral palsy: gross
      motor function classification scale.
AB  - PURPOSE: Children with cerebral palsy (CP) tend to be either excluded from
      studies of strabismus repair or pooled with children who have other neurologic
      disorders. The authors limited this study to children with defined CP to
      determine the success or failure of restoring eye alignment and fusion. METHODS:
      An observational, cross-sectional, prospective study was conducted on a
      representative cohort of 50 children. CP severity ranged from Gross Motor
      Function Classification System (GMFCS) level 1 (least severe) to 5 (most severe).
      Mean age at entrance and surgery was 3.5 years, and mean follow-up was 4.1 years
      (minimum 1 year). RESULTS: The predominant form of strabismus was infantile
      onset: esotropia in 54%, exotropia in 26%, and dyskinesia in 10%. Sixty-six
      percent of esotropic children and 61% of exotropic children achieved optimal
      (microtropic) alignment after an average of 2 and 1.8 surgical procedures,
      respectively. The likelihood of optimal alignment was similar in children with
      mild (GMFCS level 1-2) versus severe (GMFCS level 3-5) CP (P = 0.7; chi(2)).
      Irrespective of GMFCS severity, 46% of children gained binocular
      fusion/stereopsis, but the quality of fusion gained was greater in children with
      mild CP (P < 0.05). Earlier surgery was more likely to be successful (P < 0.05).
      CONCLUSIONS: Restoration of binocular alignment and a degree of fusion is a
      realistic goal in the majority of strabismic CP children. Repair may be achieved
      in children at both the mild and the severe ends of the GMFCS spectrum, without
      undue concern about treatment futility or excessive reoperation.

PMID- 21873678
TI  - The small GTPase Rap1 is a novel regulator of RPE cell barrier function.
AB  - PURPOSE: To determine whether the small GTPase Rap1 regulates the formation and
      maintenance of the retinal pigment epithelial (RPE) cell junctional barrier.
      METHODS: An in vitro model was used to study RPE barrier properties. To dissect
      the role of Rap1, two techniques were used to inhibit Rap1 function:
      overexpression of RapGAP, which acts as a negative regulator of endogenous Rap1
      activity, and treatment with engineered, adenovirally-transduced microRNAs to
      knockdown Rap1 protein expression. Transepithelial electrical resistance (TER)
      and real-time cellular analysis (RTCA) of impedance were used as readouts for
      barrier properties. Immunofluorescence microscopy was used to visualize
      localization of cadherins under steady state conditions and also during
      junctional reassembly after calcium switch. Finally, choroidal endothelial cell
      (CEC) migration across RPE monolayers was quantified under conditions of Rap1
      inhibition in RPE. RESULTS: Knockdown of Rap1 or inhibition of its activity in
      RPE reduces TER and electrical impedance of the RPE monolayers. The loss of
      barrier function is also reflected by the mislocalization of cadherins and
      formation of gaps within the monolayer. TER measurement and immunofluorescent
      staining of cadherins after a calcium switch indicate that junctional reassembly
      kinetics are also impaired. Furthermore, CEC transmigration is significantly
      higher in Rap1-knockdown RPE monolayers compared with control. CONCLUSIONS: Rap1
      GTPase is an important regulator of RPE cell junctions, and is required for
      maintenance of barrier function. This observation that RPE monolayers lacking
      Rap1 allow greater transmigration of CECs suggests a possible role for
      potentiating choroidal neovascularization during the pathology of neovascular age
      related macular degeneration.

PMID- 21873679
TI  - Elevated systemic neutrophil count in diabetic retinopathy and diabetes: a
      hospital-based cross-sectional study of 30,793 Korean subjects.
AB  - PURPOSE: To evaluate the association between systemic parameters including
      inflammatory markers and diabetic retinopathy (DR). METHODS: This was a cross
      sectional study enrolling 30,793 persons who visited a health care center for a
      medical checkup. Diabetic patients were classified into five DR groups: no DR;
      mild, moderate, or severe nonproliferative DR, and proliferative DR. A full
      laboratory workup and comprehensive medical data on the subjects were obtained
      and used for analysis. RESULTS: The mean (SD) age of the participants was 47.4
      (11.9) years (range, 18-90) and the male-to-female ratio was 55.7:44.3. The
      prevalence of diabetes and DR were 6.6% (2,020/30,793) and 5.3% (108/2,020),
      respectively. Among inflammatory markers, the mean absolute neutrophil count
      (ANC; per microliter) was significantly higher in the DR than in the non-DR group
      (3900 vs. 3566; P = 0.0143) and in diabetic than in nondiabetic subjects (3583
      vs. 3262; P < 0.0001). Subjects in the fourth quintiles of ANC showed 2.7 odds of
      having DR by multivariate analysis, and there was a linear trend in the odds
      ratios according to increasing ANC levels. The level of ANC and the ANC/leukocyte
      ratio also demonstrated a linearly increasing trend with the severity of DR, even
      after adjustment for other clinical factors, including HbA1c. Among significant
      risk factors of DR, ANC showed the second strongest predictive power for DR
      (AUROC = 0.590) after HbA1C (0.624). CONCLUSIONS: Elevated systemic neutrophil
      count is associated with the presence and severity of DR as well as diabetes.
      This result indicates that systemic subclinical inflammation is related with DR,
      and neutrophil-mediated inflammation may play an important role in the
      pathogenesis of DR.

PMID- 21873680
TI  - Reduction of apoptosis in ischemic retinas of two mouse models using hyperbaric
      oxygen treatment.
AB  - PURPOSE: To investigate the effect of hyperbaric oxygen (HBO) chamber treatment
      in mouse models of retinal ischemia. METHODS: Unilateral central retinal artery
      occlusion (CRAO) or optic nerve crush (ONC) was induced in 50 mice each, of which
      30 were treated with 100% oxygen at 2 atm for 90 minutes immediately after injury
      and then daily for up to 14 days. Mice were euthanatized on days 1, 3, and 21 for
      histologic analysis, apoptosis assay, and quantitative real-time polymerase chain
      reaction test. Findings were analyzed by injury and by treatment. RESULTS: HBO
      treatment reduced cell loss from 58% to 30% in the CRAO model and from 52% to 32%
      in the ONC model. In both models, it was associated with significantly increased
      cell survival in the retinal ganglion cell layer. Expression levels of the
      proapoptosis genes (bax, caspase-3) decreased minimally in the HBO-treated CRAO
      mice on day 1, but this trend was reversed on day 3. In the ONC group, levels of
      caspase-3, bax, and bcl-x increased on day 1 and dropped below baseline on day 3.
      The pattern of changes in the expression levels of the ischemia- and oxidative
      stress-related genes (HO-1, SOD-1, GPX-1, NOX-2) and the effectiveness of HBO
      treatment varied by model. Overall, however, gene expression levels that
      increased in the untreated mice increased further with HBO treatment and levels
      that decreased, decreased further with treatment. CONCLUSIONS: HBO treatment
      protects injured neuronal cells from apoptosis. Response to treatment differs
      molecularly after ONC or CRAO. These results should prompt clinical trials of
      acute ischemic retinal damage.

PMID- 21873681
TI  - Photochemical properties of UV Filter molecules of the human eye.
AB  - PURPOSE: To compare the photochemical properties of UV filter molecules present
      in the human lens (kynurenine, KN; 3-hydroxykynurenine, 3OHKN; 3
      hydroxykynurenine O-beta-D-glucoside, 3OHKG; 4-(2-aminophenyl)-4-oxobutanoic
      acid, AHA; and glutathionyl-kynurenine, GSH-KN) with the use of the following
      parameters: excited singlet lifetime tau(S), fluorescence quantum yield Phi(fl),
      triplet quantum yield Phi(T), and photodecomposition quantum yield Phi(dec).
      METHODS: The excited singlet lifetimes were measured with the use of fluorescence
      upconversion (time resolution, 210 fs) and pump-probe transient absorption (time
      resolution, 200 fs) methods. The fluorescence quantum yields were determined
      relative to an aqueous solution of quinine bisulfate. The triplet quantum yields
      were measured with the use of nanosecond laser flash photolysis. The
      photodecomposition quantum yields were determined by steady state photolysis
      followed by the high-performance liquid chromatography analysis. RESULTS: The
      secondary UV filters--AHA and GSH-KN are better photosensitizers than the primary
      ones--KN, 3OHKN and 3OHKG: the singlet state lifetimes of the secondary UV
      filters are longer, and the quantum yields of fluorescence and triplet state
      formation are higher. CONCLUSIONS: With aging, the ratio primary/secondary UV
      filters in the human lens decreases from approximately 10:1 to 2:1. The obtained
      results demonstrate that the quality of the secondary UV filters is inferior
      compared to the primary ones, which may result in a higher susceptibility of old
      lenses to UV light. That might be an important factor for the development of the
      age-related cataract.

PMID- 21873682
TI  - Reduced retinal neovascularization, vascular permeability, and apoptosis in
      ischemic retinopathy in the absence of prolyl hydroxylase-1 due to the prevention
      of hyperoxia-induced vascular obliteration.
AB  - PURPOSE: Prolyl hydroxylases (PHDs) are oxygen sensors that stabilize hypoxia
      inducible factors (HIFs) to induce proinflammatory, vasopermeability, and
      proapoptotic factors. These may be potential targets to reduce the complications
      of ischemic retinopathies. METHODS: Oxygen-induced ischemic retinopathy (OIR) was
      generated as a model for retinopathy of prematurity (ROP) by placing 7-day-old
      mice in 75% oxygen for 5 days and returning them to the relative hypoxia of room
      air for 5 days. Neovascularization (NV) and avascular areas were assessed on
      retinal flat-mounts by image analysis. Blood-retinal barrier breakdown was
      assessed using 3H-mannitol as a tracer. Apoptosis was detected with TUNEL
      staining. HIF-1alpha and VEGF were quantified using Western blot analysis and
      ELISA. RESULTS: PHD1-deficient mice demonstrated reduced hyperoxia-associated
      vascular obliteration during oxygen-induced ischemic retinopathy. This was
      associated with subsequent reduced avascularity, vascular leakage, and pathologic
      NV during the hypoxic phase, which could be accounted for by a reduced expression
      of HIF-1alpha and VEGF. Apoptosis in the retina was also reduced in PHD1-depleted
      mice after 2 days in hyperoxia. CONCLUSIONS: PHD1 deficiency is associated with a
      reduction of ischemia-induced retinal NV. The regulatory mechanism in this model
      appears to be: PHD1 depletion prevents HIF-1alpha degradation in hyperoxia, which
      induces VEGF, thus preventing hyperoxia-related vessel loss. Without a vessel
      deficiency, there would not be relative hypoxia when the mice are returned to
      room air and there would be no need to initiate angiogenesis signaling. Blocking
      PHD1 may be beneficial for ischemic retinopathies and inflammatory and
      neurodegenerative disorders.

PMID- 21873683
TI  - Identification of the muscarinic acetylcholine receptor subtype mediating
      cholinergic vasodilation in murine retinal arterioles.
AB  - PURPOSE: To identify the muscarinic acetylcholine receptor subtype that mediates
      cholinergic vasodilation in murine retinal arterioles. METHODS: Muscarinic
      receptor gene expression was determined in murine retinal arterioles using real
      time PCR. To assess the functional relevance of muscarinic receptors for
      mediating vascular responses, retinal vascular preparations from muscarinic
      receptor-deficient mice were studied in vitro. Changes in luminal arteriole
      diameter in response to muscarinic and nonmuscarinic vasoactive substances were
      measured by video microscopy. RESULTS: Only mRNA for the M(3) receptor was
      detected in retinal arterioles. Thus, M(3) receptor-deficient mice (M3R(-/-)) and
      respective wild-type controls were used for functional studies. Acetylcholine
      concentration-dependently dilated retinal arterioles from wild-type mice. In
      contrast, vasodilation to acetylcholine was almost completely abolished in
      retinal arterioles from M3R(-/-) mice, whereas responses to the nitric oxide (NO)
      donor nitroprusside were retained. Carbachol, an acetylcholinesterase-resistant
      analog of acetylcholine, also evoked dilation in retinal arterioles from wild
      type, but not from M3R(-/-), mice. Vasodilation responses from wild-type mice to
      acetylcholine were negligible after incubation with the non-subtype-selective
      muscarinic receptor blocker atropine or the NO synthase inhibitor N(omega)-nitro
      L-arginine methyl ester, and were even reversed to contraction after endothelial
      damage with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate.
      CONCLUSIONS: These findings provide evidence that endothelial M(3) receptors
      mediate cholinergic vasodilation in murine retinal arterioles via activation of
      NO synthase.

PMID- 21873684
TI  - Gene expression profiling of the retina after transcorneal electrical stimulation
      in wild-type Brown Norway rats.
AB  - PURPOSE: Transcorneal electrical stimulation (TES) has been beneficial in several
      neurodegenerative ocular diseases, but the exact mechanisms remain to be
      elucidated. This study was conducted to investigate the effects of TES on the
      retinas of wild-type Brown Norway (BN) rats by gene expression profiling and to
      assess its effects on retinal function and morphology. METHODS: TES was applied
      to BN wild-type rat retinas in vivo for 1 hour (1-ms biphasic pulses at 20 Hz;
      200 MUA). RNA was isolated and processed for microarray-based profiling 4 hours
      after TES; differentially expressed genes from TES compared with those from sham
      treated animals were validated by quantitative real-time polymerase chain
      reaction. Furthermore, the effect of TES was assessed at the structural and
      functional levels using electroretinography, confocal scanning laser
      ophthalmoscopy, optical coherence tomography, and immunohistochemistry. RESULTS:
      Transcriptome changes associated with TES versus sham-stimulated BN wild-type
      retina were identified. Four hundred ninety genes were differentially expressed
      in TES and included potentially neuroprotective genes such as Bax or members of
      the tumor necrosis factor family (Tnfrsf11b, Tnrsf12a, Tnfsf13b, Tnfsf13). ERG
      recordings showed physiological retinal function after TES, and structural in
      vivo and ex vivo studies revealed intact retinal anatomy. CONCLUSIONS: These
      results demonstrate that TES applied to the retina of the wild-type BN rats
      induces distinct transcriptome level changes and may help in the understanding of
      the mechanisms underlying TES. In addition, TES treatment indicates no negative
      effect on structure and function of the wild-type BN retina up to 35 hours after
      application.

PMID- 21873685
TI  - Assessment of cone survival in response to CNTF, GDNF, and VEGF165b in a novel ex
      vivo model of end-stage retinitis pigmentosa.
AB  - PURPOSE: To develop a robust ex vivo model for evaluating cone survival in end
      stage retinitis pigmentosa (RP) and apply this to quantify the effects of
      putative neuroprotective compounds. METHODS: Rhodopsin knockout mice were crossed
      with OPN1-GFP reporter mice so that GFP-positive cones could be identified
      against the background of a rod-specific degeneration. Retinal explants were
      harvested from 10-week-old mice and maintained in organotypic culture. Ciliary
      neurotrophic factor (CNTF), glial cell-derived neurotrophic factor (GDNF), or
      vascular endothelial growth factor 165b (VEGF(165b)) was administered daily to
      treatment groups at three doses (200 ng/mL, 100 ng/mL, or 50 ng/mL; n = 5
      explants per group). Fluorescence microscopy was performed on days 1, 3, 5, 7, 9,
      and 12 to document the number of GFP-expressing cones. RESULTS: Cone survival
      could be assessed reliably and reproducibly in this model, and cone degeneration
      was significantly greater in the absence of rods, in keeping with clinical
      observations of RP. Daily administration of 200 ng/mL CNTF led to significantly
      increased cone survival compared with sham-treated controls. The effect was dose
      dependent; 100 ng/mL CNTF reduced cone loss but to a lesser extent, and 200 ng/mL
      GDNF showed significant protection against cone loss at later time points (day 9
      12) but was much less effective than CNTF at all doses. VEGF(165b) showed no
      neuroprotective effect in this model at any dose. CONCLUSIONS: This model allows
      precise quantification of the neuroprotective effects of various compounds on
      cone survival and may therefore provide a robust method of screening
      neuroprotective compounds before application in vivo.

PMID- 21873686
TI  - An unusual case of acute tetraparesis.

PMID- 21873687
TI  - Falling weight Z-scores in the postnatal period need careful interpretation.

PMID- 21873688
TI  - A pivotal role for antigen-presenting cells overexpressing SOCS3 in controlling
      invariant NKT cell responses during collagen-induced arthritis.
AB  - OBJECTIVE: Suppressor of cytokine signalling (SOCS) proteins constitute a class
      of intracellular proteins that are key physiological regulators of immune cell
      function. It has previously been shown that antigen-presenting cells (APCs)
      overexpressing SOCS3 steer T helper immune responses and protect against
      experimental arthritis. A study was undertaken to investigate the contribution of
      SOCS3 in regulating invariant natural killer T (iNKT) cell responses during
      collagen-induced arthritis (CIA). METHODS: DBA/1 mice were immunised with type II
      collagen and adenoviruses encoding SOCS3 were administered intravenously before
      the clinical onset of arthritis. Murine APCs overexpressing SOCS3 were co
      cultured with an iNKT cell hybridoma and interleukin 2 (IL-2) release was
      measured by Luminex multi-analyte technology. The frequency and activation of
      primary iNKT cells was assessed by flow cytometry. Murine APCs were analysed for
      cytokine and CD1d expression following viral SOCS3 gene transfer. RESULTS: Viral
      overexpression of SOCS3 in APCs resulted in reduced activation of the iNKT cell
      hybridoma. Importantly, during initiation of CIA, adenovirus-mediated
      overexpression of SOCS3 in hepatic and splenic APCs inhibited iNKT cell expansion
      in both organs. The iNKT cell population from SOCS3-treated mice showed low
      expression of the early activation marker CD69 and primary liver iNKT cells
      produced less interferon gamma and IL-4 upon alpha-galactosylceramide
      stimulation. No differences in CD1d surface expression were observed, but SOCS3
      transduced APCs produced decreased levels of proinflammatory cytokines and
      increased levels of IL-10. CONCLUSION: These results demonstrate a critical role
      for SOCS3 in controlling the immunostimulatory capacities of APCs, which has
      direct implications for the effector function of iNKT cells during arthritis.

PMID- 21873689
TI  - A large-scale association study identified multiple HLA-DRB1 alleles associated
      with ACPA-negative rheumatoid arthritis in Japanese subjects.
AB  - BACKGROUND: HLA-DRB1 is associated with rheumatoid arthritis (RA). However, it
      has recently been suggested that HLA-DRB1 is only associated with patients with
      RA who have anticitrullinated peptide/protein antibodies (ACPA), which are
      specific to RA. OBJECTIVE: To elucidate whether specific HLA-DR alleles are
      associated with ACPA-negative RA development. METHODS: HLA-DRB1 typing was
      carried out in 368 Japanese ACPA-negative patients with RA and 1508 healthy
      volunteers as the first set, followed by HLA-DRB1 typing of 501 cases and 500
      controls as the second set. The HLA-DRB1 allele frequency and diplotype frequency
      were compared in each group, and the results of the two studies were combined to
      detect HLA-DRB1 alleles or diplotypes associated with ACPA-negative RA. RESULTS:
      HLA-DRB1*12:01 was identified as a novel susceptibility allele for ACPA-negative
      RA (p=0.000088, OR=1.72, 95% CI 1.31 to 2.26). HLA-DRB1*04:05 and *14:03 showed
      moderate associations with ACPA-negative RA (p=0.0063, OR=1.26, 95% CI 1.07 to
      1.49 and p=0.0043, OR=1.81, 95% CI 1.20 to 2.73, respectively). The shared
      epitope was weakly associated with ACPA-negative RA, but no dosage effect was
      detected (p=0.016, OR=1.17, 95% CI 1.03 to 1.34). A combination of HLA-DRB1*12:01
      and DRB1*09:01 showed a strong association with susceptibility to ACPA-negative
      RA (p=0.00013, OR=3.62, 95% CI 1.79 to 7.30). Homozygosity for HLA-DR8 was
      significantly associated with ACPA-negative RA (p=0.0070, OR=2.16, 95% CI 1.22 to
      3.82). It was also found that HLA-DRB1*15:02 and *13:02 were protective against
      ACPA-negative RA (p=0.00010, OR=0.68, 95% CI 0.56 to 0.83 and p=0.00059, OR=0.66,
      95% CI 0.52 to 0.84, respectively). CONCLUSIONS: In this large-scale association
      study multiple alleles and diplotypes were found to be associated with
      susceptibility to, or protection against, ACPA-negative RA.

PMID- 21873690
TI  - Enthesis erosion in spondyloarthritis is not a persistent structural lesion.
AB  - OBJECTIVE: To evaluate the ability of ultrasound (US) to detect the presence and
      change of Achilles erosions in spondyloarthritis (SpA). METHODS: A blind
      prospective two-dimensional (2D) and three-dimensional (3D) US study of Achilles
      enthesis erosions in early SpA was undertaken. US examinations were performed at
      baseline and at 6 and 12 months of follow-up. Clinical outcomes measures were
      collected. RESULTS: Bilateral Achilles entheses of 68 patients (35 women) were
      investigated. The mean Bath Ankylosing Spondylitis Disease Activity Index and C
      reactive protein (CRP) levels were 4.58 +/- 2.05 and 5.97 +/- 9.91 mg/l,
      respectively. The kappa values for intrareader agreement for 2D and 3D images
      were 0.84 and 0.85 for two readers. 2D US visualised 10 erosions (7.4%) and 3D US
      visualised 13 erosions (9.6%) in 10 patients (14.7%). At 6 and 12 months of
      follow-up, 25% and 50% of basal erosions had disappeared, respectively and, of
      the new erosions that appeared at 6 months, 40% had disappeared 6 months later. A
      statistically significant association between erosion and CRP levels, entheseal
      Doppler signals and the number of tender and swollen joints was found.
      CONCLUSIONS: US examination of Achilles erosions is reliable and sensitive to
      change. An association was found between Achilles erosions and objective activity
      based measurements of SpA outcomes.

PMID- 21873691
TI  - Child marriage in the United States and its association with mental health in
      women.
AB  - OBJECTIVE: Despite the devastating impact of child marriage (marriage before the
      age of 18 years) on health, no study has yet evaluated its impact on mental
      health in the general adult population. This article presents nationally
      representative data on the prevalence, sociodemographic correlates, and
      psychiatric comorbidity of child marriage among women in the United States.
      METHODS: Data were drawn from the 2001-2002 National Epidemiologic Survey on
      Alcohol and Related Conditions. We limited our analyses to the sample of women (N
      = 24 575) with a known age at first marriage, of whom 18 645 had been or were
      presently married. RESULTS: The prevalence of child marriage among women was
      8.9%. Demographic factors associated with child marriage were black and American
      Indian/Alaska Native ethnicities, age at interview of >45 years, low educational
      level, low income, and living in the South and rural areas of the United States.
      The overall lifetime and 12-month rates of psychiatric disorders were higher for
      women who married as children, compared with women who married as adults. In
      addition, women who married as children were more likely to seek and access
      health services, compared with women who married in adulthood. CONCLUSIONS: Child
      marriage increases the risk of lifetime and current psychiatric disorders in the
      United States. Support for psychiatric vulnerabilities among women married in
      childhood is required.

PMID- 21873692
TI  - Policy statement-Prevention of varicella: update of recommendations for use of
      quadrivalent and monovalent varicella vaccines in children.
AB  - Two varicella-containing vaccines are licensed for use in the United States:
      monovalent varicella vaccine (Varivax [Merck & Co, Inc, West Point, PA]) and
      quadrivalent measles-mumps-rubella-varicella vaccine (MMRV) (ProQuad [Merck & Co,
      Inc]). It is estimated from postlicensure data that after vaccination at 12
      through 23 months of age, 7 to 9 febrile seizures occur per 10,000 children who
      receive the MMRV, and 3 to 4 febrile seizures occur per 10,000 children who
      receive the measles-mumps-rubella (MMR) and varicella vaccines administered
      concurrently but at separate sites. Thus, 1 additional febrile seizure is
      expected to occur per approximately 2300 to 2600 children 12 to 23 months old
      vaccinated with the MMRV, when compared with separate MMR and varicella vaccine
      administration. The period of risk for febrile seizures is from 5 through 12 days
      after receipt of the vaccine(s). No increased risk of febrile seizures is seen
      among patients 4 to 6 years of age receiving MMRV. Febrile seizures do not
      predispose to epilepsy or neurodevelopmental delays later in life and are not
      associated with long-term health impairment. The American Academy of Pediatrics
      recommends that either MMR and varicella vaccines separately or the MMRV be used
      for the first dose of measles, mumps, rubella, and varicella vaccines
      administered at 12 through 47 months of age. For the first dose of measles,
      mumps, rubella, and varicella vaccines administered at ages 48 months and older,
      and for dose 2 at any age (15 months to 12 years), use of MMRV generally is
      preferred over separate injections of MMR and varicella vaccines.

PMID- 21873693
TI  - Urinary tract infection: clinical practice guideline for the diagnosis and
      management of the initial UTI in febrile infants and children 2 to 24 months.
AB  - OBJECTIVE: To revise the American Academy of Pediatrics practice parameter
      regarding the diagnosis and management of initial urinary tract infections (UTIs)
      in febrile infants and young children. METHODS: Analysis of the medical
      literature published since the last version of the guideline was supplemented by
      analysis of data provided by authors of recent publications. The strength of
      evidence supporting each recommendation and the strength of the recommendation
      were assessed and graded. RESULTS: Diagnosis is made on the basis of the presence
      of both pyuria and at least 50,000 colonies per mL of a single uropathogenic
      organism in an appropriately collected specimen of urine. After 7 to 14 days of
      antimicrobial treatment, close clinical follow-up monitoring should be maintained
      to permit prompt diagnosis and treatment of recurrent infections. Ultrasonography
      of the kidneys and bladder should be performed to detect anatomic abnormalities.
      Data from the most recent 6 studies do not support the use of antimicrobial
      prophylaxis to prevent febrile recurrent UTI in infants without vesicoureteral
      reflux (VUR) or with grade I to IV VUR. Therefore, a voiding cystourethrography
      (VCUG) is not recommended routinely after the first UTI; VCUG is indicated if
      renal and bladder ultrasonography reveals hydronephrosis, scarring, or other
      findings that would suggest either high-grade VUR or obstructive uropathy and in
      other atypical or complex clinical circumstances. VCUG should also be performed
      if there is a recurrence of a febrile UTI. The recommendations in this guideline
      do not indicate an exclusive course of treatment or serve as a standard of care;
      variations may be appropriate. Recommendations about antimicrobial prophylaxis
      and implications for performance of VCUG are based on currently available
      evidence. As with all American Academy of Pediatrics clinical guidelines, the
      recommendations will be reviewed routinely and incorporate new evidence, such as
      data from the Randomized Intervention for Children With Vesicoureteral Reflux
      (RIVUR) study. CONCLUSIONS: Changes in this revision include criteria for the
      diagnosis of UTI and recommendations for imaging.

PMID- 21873694
TI  - Technical report-Diagnosis and management of an initial UTI in febrile infants
      and young children.
AB  - OBJECTIVES: The diagnosis and management of urinary tract infections (UTIs) in
      young children are clinically challenging. This report was developed to inform
      the revised, evidence-based, clinical guideline regarding the diagnosis and
      management of initial UTIs in febrile infants and young children, 2 to 24 months
      of age, from the American Academy of Pediatrics Subcommittee on Urinary Tract
      Infection. METHODS: The conceptual model presented in the 1999 technical report
      was updated after a comprehensive review of published literature. Studies with
      potentially new information or with evidence that reinforced the 1999 technical
      report were retained. Meta-analyses on the effectiveness of antimicrobial
      prophylaxis to prevent recurrent UTI were performed. RESULTS: Review of recent
      literature revealed new evidence in the following areas. Certain clinical
      findings and new urinalysis methods can help clinicians identify febrile children
      at very low risk of UTI. Oral antimicrobial therapy is as effective as parenteral
      therapy in treating UTI. Data from published, randomized controlled trials do not
      support antimicrobial prophylaxis to prevent febrile UTI when vesicoureteral
      reflux is found through voiding cystourethrography. Ultrasonography of the
      urinary tract after the first UTI has poor sensitivity. Early antimicrobial
      treatment may decrease the risk of renal damage from UTI. CONCLUSIONS: Recent
      literature agrees with most of the evidence presented in the 1999 technical
      report, but meta-analyses of data from recent, randomized controlled trials do
      not support antimicrobial prophylaxis to prevent febrile UTI. This finding argues
      against voiding cystourethrography after the first UTI.

PMID- 21873695
TI  - Sleep disorders in children: a national assessment of primary care pediatrician
      practices and perceptions.
AB  - OBJECTIVES: To assess general pediatricians' screening practices for sleep
      related issues and assess their knowledge on common sleep complaints in children,
      their perceived barriers to screening for sleep issues, and whether they have
      received training regarding sleep issues. METHODS: A national random sample (n =
      700) of general pediatricians who were members of the American Academy of
      Pediatrics were sent a valid and reliable questionnaire on sleep problems in
      youth. RESULTS: A total of 346 pediatricians (49%) responded. The vast majority
      (96%) indicated that they believed it was their job to counsel patients/guardians
      regarding sleep hygiene, yet few pediatricians (18%) had ever received formal
      training on sleep disorders. Those who did not screen for sleep problems spent
      significantly less time with each patient and perceived significantly more
      barriers to screening. Pediatricians who had received training about sleep
      disorders had significantly higher knowledge scores on sleep problems, perceived
      significantly fewer barriers to screening, and reported significantly higher
      confidence scores regarding counseling patients/guardians on sleep problems.
      CONCLUSION: These findings support the need for formal education on sleep
      disorders for all pediatricians.

PMID- 21873696
TI  - The first measles vaccine.

PMID- 21873697
TI  - Policy statement-Boxing participation by children and adolescents.
AB  - Thousands of boys and girls younger than 19 years participate in boxing in North
      America. Although boxing provides benefits for participants, including exercise,
      self-discipline, and self-confidence, the sport of boxing encourages and rewards
      deliberate blows to the head and face. Participants in boxing are at risk of
      head, face, and neck injuries, including chronic and even fatal neurologic
      injuries. Concussions are one of the most common injuries that occur with boxing.
      Because of the risk of head and facial injuries, the American Academy of
      Pediatrics and the Canadian Paediatric Society oppose boxing as a sport for
      children and adolescents. These organizations recommend that physicians
      vigorously oppose boxing in youth and encourage patients to participate in
      alternative sports in which intentional head blows are not central to the sport.

PMID- 21873698
TI  - The new American Academy of Pediatrics urinary tract infection guideline.

PMID- 21873699
TI  - Premasticating food for weaning African infants: a possible vehicle for
      transmission of HIV.
AB  - BACKGROUND: Although premastication of food for weaning infants might have
      nutritional benefit, it is also associated with transmission of pathogens. We
      investigated premastication practices in Cape Town, South Africa, in lower
      socioeconomic status caregivers of infants below 2 years of age. METHODS: A
      previously reported questionnaire was adapted for South African conditions. A
      convenience sample of infant caregivers was captured at public maternal/pediatric
      and HIV outpatient clinics and home visits. RESULTS: We interviewed 154
      caregivers, 92% of whom were the biological mothers (median age: 29). Of these,
      70% were black, and 29% were colored. There were 106 (69%) caregivers who
      practiced premastication. The median age of infants who received premasticated
      food was 6 (interquartile range: 4-6) months. Forty-six (43%) infants were
      teething, and 44 (42%) had oral mucosal lesions while receiving premasticated
      food. Fifty-five (52%) caregivers reported an oral condition, mostly bleeding
      gums, mouth sores, and thrush, and 41 (39%) caregivers reported blood in the
      food. Premasticating caregivers had a significantly lower educational level than
      those caregivers who did not engage in this practice. Premastication practices
      were cultural (40%), habit (20%), and on mother's advice (75%). Reasons for
      premastication were to pretaste (68%), encourage eating (61%), estimate food
      temperature (85%), and homogenize food (60%). CONCLUSIONS: Counselors and
      caregivers should be aware of the adverse effects of premastication. Education
      should include advice to avoid premastication and to seek health advice for oral
      conditions in the caregiver and child. More studies are needed to better define
      the extent and risks of premastication, including its possible role in increasing
      HIV-1 transmission.

PMID- 21873700
TI  - Policy statement-Professional liability insurance and medicolegal education for
      pediatric residents and fellows.
AB  - The American Academy of Pediatrics believes that pediatric residents and fellows
      should be fully informed of the scope and limitations of their professional
      liability insurance coverage while in training. The academy states that residents
      and fellows should be educated by their training institutions on matters relating
      to medical liability and the importance of maintaining adequate and continuous
      professional liability insurance coverage throughout their careers in medicine.

PMID- 21873701
TI  - Relationship of maternal snuff use and cigarette smoking with neonatal apnea.
AB  - BACKGROUND: Maternal smoking is associated with disturbed cardiorespiratory
      control in the infant. Despite lacking knowledge of whether the harmful effects
      of smoking are caused by combustion products in tobacco smoke or by nicotine, it
      has been argued that nicotine-replacement therapy during pregnancy is safer than
      smoking. OBJECTIVE: The goal of this study was to investigate if the disturbances
      in cardiorespiratory control associated with maternal smoking are also seen in
      infants prenatally exposed to snuff. We hypothesized that prenatal nicotine
      exposure (via moist snuff) causes disturbances in autonomic control and thereby
      increases the risk of apnea in the newborn. METHODS: In a nationwide Swedish
      cohort study, we studied associations between maternal tobacco use during
      pregnancy and neonatal apnea. Of 609 551 live-born singleton infants, 7599 were
      born to snuff-using mothers, 41 391 and 16 928 were born to light (1-9 cigarettes
      per day) and heavy (>= 10 cigarettes per day) smokers, respectively. Logistic
      regression was used to calculate odds ratios, using 95% confidence intervals.
      RESULTS: Compared with infants of nontobacco users, infants with prenatal
      exposure to snuff were at an increased risk of apnea even after adjustment for
      differences in gestational age (odds ratio: 1.96 [95% confidence interval: [1.30
      2.96]) Smoking was associated with increased risk of apnea before, but not after,
      adjusting for gestational age. CONCLUSIONS: Snuff use during pregnancy is
      associated with a higher risk of neonatal apnea than smoking. Maternal use of
      snuff or nicotine-replacement therapy cannot be regarded as an alternative to
      smoking during pregnancy.

PMID- 21873702
TI  - Decreasing rate of biliary atresia in Taiwan: a survey, 2004-2009.
AB  - OBJECTIVES: The pathogenesis of biliary atresia (BA) is unclear, but
      epidemiological studies may help to elucidate possible causes. The goals of this
      study were to identify BA incidence changes in Taiwan in 2004-2009 and to survey
      the factors that might influence incidence changes to elucidate the possible
      causes of BA. METHODS: A Taiwan national registry system for BA has been
      established since 2004. By using data from the national registry system for BA,
      we identified BA incidence changes in 2004-2009. We also evaluated the
      correlations between BA incidences and estimated rotavirus vaccine coverage rates
      and between BA incidences and the gross domestic product. RESULTS: A total of 185
      patients with BA were identified in 2004-2009 in Taiwan, whereas the number of
      live births was 1 221 189. Compared with the incidence of BA in 2004-2006 (1.79
      cases per 10,000 live births), the incidence of BA in 2007-2009 (1.23 cases per
      10,000 live births) was decreased significantly (P = .01). BA incidences were
      negatively correlated with the gross domestic product (P = .02) and marginally
      negatively correlated with rotavirus vaccine coverage rates (P = .07).
      CONCLUSIONS: A significant decrease in BA incidence in Taiwan since 2007 has been
      noted and may be related to improvements in the general socioeconomic status and
      the popularity of rotavirus vaccination. Although more evidence is needed to
      establish a direct correlation, this phenomenon may shed light on possible causes
      of and preventive interventions for BA.

PMID- 21873703
TI  - Transcutaneous bilirubin in exclusively breastfed healthy term newborns up to 12
      days of life.
AB  - OBJECTIVE: To determine the curve of transcutaneous bilirubin in breastfed term
      neonates up to 12 days of life. METHODS: In a prospective cohort study, we
      performed a 12-day evaluation of 223 healthy, exclusively breastfed, appropriate
      for-gestational-age neonates who roomed-in for at least 48 hours. Each newborn
      had forehead transcutaneous bilirubin and body weight measured at the end of 1,
      2, 3, 4, 5, 6, 8, 10, and 12 days. Regression analysis was used with bilirubin as
      a third-degree polynomial function of time. The 25th, 50th, 75th, 90th, and 95th
      percentile curves were constructed by using the residual mean square for each
      day. RESULTS: Patients were 46% white, 34% mixed race, and 20% black, the mean
      birth weight was 3260 g (range: 2560-4090 g), the mean gestational age was 39.4
      weeks (range: 37.0-41.9 weeks), 51% were male, 74% were born by vaginal delivery,
      and 66% had been breastfed since delivery. The mean highest weight loss was 4.7%
      (range: 1%-12%) at the second or third day, and in most infants the weight
      returned to the birth weight at the fifth day. With 2007 total bilirubin
      measurements, bilirubin concentrations reached the 50th percentile level (5.6
      mg/dL) at the third and fourth days and returned to the 24-hour level (4.8 mg/dL)
      at the sixth day. The 95th percentile bilirubin level was 8.2 mg/dL at 24 hours
      of life, reached 12.2 mg/dL on the fourth day, and declined to 8.5 mg/dL on the
      12th day. CONCLUSIONS: The transcutaneous bilirubin curve represents the natural
      history of bilirubinemia in exclusively breastfed healthy term newborns in the
      first 12 days of life.

PMID- 21873704
TI  - Clinical report-Guidelines for the determination of brain death in infants and
      children: an update of the 1987 task force recommendations.
AB  - OBJECTIVE: To review and revise the 1987 pediatric brain death guidelines.
      METHODS: Relevant literature was reviewed. Recommendations were developed using
      the GRADE system. CONCLUSIONS AND RECOMMENDATIONS: (1) Determination of brain
      death in term newborns, infants and children is a clinical diagnosis based on the
      absence of neurologic function with a known irreversible cause of coma. Because
      of insufficient data in the literature, recommendations for preterm infants less
      than 37 weeks gestational age are not included in this guideline. (2)
      Hypotension, hypothermia, and metabolic disturbances should be treated and
      corrected and medications that can interfere with the neurologic examination and
      apnea testing should be discontinued allowing for adequate clearance before
      proceeding with these evaluations. (3) Two examinations including apnea testing
      with each examination separated by an observation period are required.
      Examinations should be performed by different attending physicians. Apnea testing
      may be performed by the same physician. An observation period of 24 hours for
      term newborns (37 weeks gestational age) to 30 days of age, and 12 hours for
      infants and chi (> 30 days to 18 years) is recommended. The first examination
      determines the child has met the accepted neurologic examination criteria for
      brain death. The second examination confirms brain death based on an unchanged
      and irreversible condition. Assessment of neurologic function following
      cardiopulmonary resuscitation or other severe acute brain injuries should be
      deferred for 24 hours or longer if there are concerns or inconsistencies in the
      examination. (4) Apnea testing to support the diagnosis of brain death must be
      performed safely and requires documentation of an arterial Paco(2) 20 mm Hg above
      the baseline and >= 60 mm Hg with no respiratory effort during the testing
      period. If the apnea test cannot be safely completed, an ancillary study should
      be performed. (5) Ancillary studies (electroencephalogram and radionuclide
      cerebral blood flow) are not required to establish brain death and are not a
      substitute for the neurologic examination. Ancillary studies may be us d to
      assist the clinician in making the diagnosis of brain death (i) when components
      of the examination or apnea testing cannot be completed safely due to the
      underlying medical condition of the patient; (ii) if there is uncertainty about
      the results of the neurologic examination; (iii) if a medication effect may be
      present; or (iv) to reduce the inter-examination observation period. When
      ancillary studies are used, a second clinical examination and apnea test should
      be performed and components that can be completed must remain consistent with
      brain death. In this instance the observation interval may be shortened and the
      second neurologic examination and apnea test (or all components that are able to
      be completed safely) can be performed at any time thereafter. (6) Death is
      declared when the above criteria are fulfilled.

PMID- 21873705
TI  - Colchicine for recurrent pericarditis (CORP): a randomized trial.
AB  - BACKGROUND: Recurrence is the most common complication of pericarditis, affecting
      10% to 50% of patients. OBJECTIVE: To evaluate the efficacy and safety of
      colchicine for the secondary prevention of recurrent pericarditis. DESIGN:
      Prospective, randomized, double-blind, placebo-controlled multicenter trial.
      (ClinicalTrials.gov registration number: NCT00128414) SETTING: 4 general
      hospitals in urban areas of Italy. PATIENTS: 120 patients with a first recurrence
      of pericarditis. INTERVENTION: In addition to conventional treatment, patients
      were randomly assigned to receive either placebo or colchicine, 1.0 to 2.0 mg on
      the first day followed by a maintenance dose of 0.5 to 1.0 mg/d, for 6 months.
      MEASUREMENTS: The primary study end point was the recurrence rate at 18 months.
      Secondary end points were symptom persistence at 72 hours, remission rate at 1
      week, number of recurrences, time to first recurrence, disease-related
      hospitalization, cardiac tamponade, and rate of constrictive pericarditis.
      RESULTS: At 18 months, the recurrence rate was 24% in the colchicine group and
      55% in the placebo group (absolute risk reduction, 0.31 [95% CI, 0.13 to 0.46];
      relative risk reduction, 0.56 [CI, 0.27 to 0.73]; number needed to treat, 3 [CI,
      2 to 7]). Colchicine reduced the persistence of symptoms at 72 hours (absolute
      risk reduction, 0.30 [CI, 0.13 to 0.45]; relative risk reduction, 0.56 [CI, 0.27
      to 0.74]) and mean number of recurrences, increased the remission rate at 1 week,
      and prolonged the time to subsequent recurrence. The study groups had similar
      rates of side effects and drug withdrawal. LIMITATION: Multiple recurrences and
      neoplastic or bacterial causes were excluded. CONCLUSION: Colchicine is safe and
      effective for secondary prevention of recurrent pericarditis.

PMID- 21873706
TI  - Summaries for patients. Colchicine treatment for recurrent pericarditis.

PMID- 21873707
TI  - Atrial fibrillation, moderate chronic kidney disease, and stroke prevention: new
      anticoagulants, new hope.

PMID- 21873708
TI  - Prevention of stroke and systemic embolism with rivaroxaban compared with
      warfarin in patients with non-valvular atrial fibrillation and moderate renal
      impairment.
AB  - AIMS: Patients with non-valvular atrial fibrillation (AF) and renal insufficiency
      are at increased risk for ischaemic stroke and bleeding during anticoagulation.
      Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the
      liver, preserves the benefit of warfarin for stroke prevention while causing
      fewer intracranial and fatal haemorrhages. METHODS AND RESULTS: We randomized 14
      264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [15 mg/day
      if creatinine clearance (CrCl) 30-49 mL/min] or dose-adjusted warfarin (target
      international normalized ratio 2.0-3.0). Compared with patients with CrCl >50
      mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were
      older (79 years) and had higher event rates irrespective of study treatment.
      Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic
      embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs.
      2.77 per 100 patient-years with warfarin [hazard ratio (HR) 0.84; 95% confidence
      interval (CI) 0.57-1.23] in the per-protocol population. Intention-to-treat
      analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol
      results. Rates of the principal safety endpoint (major and clinically relevant
      non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P = 0.76) and
      intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P = 0.54) were
      similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100
      patient-years; P = 0.047) occurred less often with rivaroxaban. CONCLUSION:
      Patients with AF and moderate renal insufficiency have higher rates of stroke and
      bleeding than those with normal renal function. There was no evidence of
      heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET
      AF yielded results consistent with the overall trial in comparison with dose
      adjusted warfarin.

PMID- 21873709
TI  - Long-term results from statin trials: answers but more unresolved questions.

PMID- 21873711
TI  - eComment: Lymph node dissection or sampling in patients with non-small cell lung
      cancer?

PMID- 21873710
TI  - The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the
      lipid-lowering arm in the U.K.
AB  - AIMS: The aim of this study was to determine the outcome benefits in those
      originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial
      8 years after closure of the lipid-lowering arm (LLA) of the trial (ASCOT-LLA)
      among the U.K. population. METHODS AND RESULTS: ASCOT-LLA was a factorially
      designed double-blind placebo-controlled trial of atorvastatin in 10 305
      hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm (BPLA)
      of the trial and with total cholesterol concentrations, at baseline, of <6.5
      mmol/L. ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up
      because of a 36% relative risk reduction (RRR) in non-fatal myocardial infarction
      and fatal coronary heart disease (CHD) (the primary outcome) in favour of
      atorvastatin and a non-significant reduction in CV deaths (16%) and all-cause
      mortality (13%). After a further 2.2 years at the end of ASCOT-BPLA, despite
      extensive crossovers from and to statin usage, the RRR in all endpoints remained
      essentially unchanged. A median 11 years after initial randomization and ~8 years
      after closure of LLA, all-cause mortality (n=520 and 460 in placebo and
      atorvastatin, respectively) remained significantly lower in those originally
      assigned atorvastatin (HR 0.86, CI 0.76-0.98, P=0.02). CV deaths were fewer, but
      not significant (HR 0.89, CI 0.72-1.11, P=0.32) and non-CV deaths were
      significantly lower (HR 0.85, CI 0.73-0.99, P=0.03) in those formerly assigned
      atorvastatin attributed to a reduction in deaths due to infection and respiratory
      illness. CONCLUSION: Legacy effects of those originally assigned atorvastatin may
      contribute to long-term benefits on all-cause mortality. An explanation for long
      term benefits on non-CV deaths has not been established.

PMID- 21873712
TI  - eComment: Early stentless aortic prosthesis dysfunction due to interlayer
      hematoma formation.

PMID- 21873713
TI  - The conservative management of primary pyomyositis abscess in children: case
      series and review of the literature.
AB  - Pyomyositis is a primary pyogenic infection in skeletal muscle, often progressing
      to abscess formation. It is rare in temperate climates and generally deep-seated
      within the pelvis with non-specific clinical features, making diagnosis
      difficult. Magnetic resonance imaging (MRI) is highly sensitive for muscle
      inflammation and fluid collection, and with its increasing availability is now
      the investigation of choice. Treatment of pyomyositis abscess has traditionally
      been with incision and drainage or guided aspiration followed by a prolonged
      course of antibiotics, although there are sporadic reports of cases treated
      successfully with antibiotics alone. Our aim was to describe our own experience
      with the treatment of pyomyositis abscess in children. From our 20-year database
      of over 16,000 paediatric orthopaedic admissions, we identified only three cases
      with MRI-confirmed pyomyositis abscess. These were all in boys (aged 2-12 years)
      and affected the gluteal, piriformis and adductor muscles. Despite the organisms
      not being identified, each patient was treated successfully with a short (4-7
      days) course of intravenous antibiotics followed by 2-6 weeks of oral therapy.
      There were no recurrences or complications and all made a full recovery. In
      conclusion, we propose that uncomplicated pyomyositis abscess in children may
      usually be managed conservatively without the need for open or percutaneous
      drainage.

PMID- 21873714
TI  - The antenatal detection rate of major congenital heart disease in Scotland.
AB  - Ultrasonography has been used to detect fetal congenital heart disease since the
      1980s, although there has been little uniformity in policy. In the UK, data
      published for 1993-1995 found an average detection rate of 23.4% with a Scottish
      rate of 9.6%. At the time of this study, 10 out of the 14 health boards in
      Scotland were implementing the 16-22-week fetal anomaly scan (FAS). The aims of
      this study were to determine the rate of antenatal diagnosis of major congenital
      heart disease (MCHD) throughout Scotland during 1 January to 31 December 2006, to
      document the regional differences in detection and to determine if implementation
      of a FAS significantly improved rates. Retrospective data were collected from the
      centralized Paediatric Cardiac Services in Edinburgh and Glasgow. The database
      contains information on all infants with cardiac disease in Scotland. All infants
      requiring cardiac intervention or dying in the first year of life were included.
      The results showed that the antenatal diagnosis rate for Scotland was 28% (95% CI
      21.2%, 34.9%). The Scottish health boards that had implemented the FAS had a
      significantly higher antenatal detection rate (chi(2) test P = 0.037). In
      conclusion, antenatal detection rate of MCHD varies widely throughout Scotland.
      Implementation of the FAS has made a significant difference to antenatal
      diagnosis.

PMID- 21873715
TI  - Referrals to a liaison psychiatry outpatient clinic.
AB  - This study aimed to describe the demographic and clinical characteristics of
      consecutive referrals to a liaison psychiatry outpatient clinic, based within a
      National Health Service (NHS) general hospital. All outpatient referrals to the
      service between January 2005 and January 2008 were subjected to retrospective
      completion of a proforma for post hoc data collection. Data relating to
      characteristics of the referral, patients, diagnosis, and nature and extent of
      contact were extracted for scrutiny. The majority (60.2%) of referrals to the
      service came from physicians based within the general hospital. Where conveyed,
      depression (26.7%) was the most commonly cited reason for referral. Diagnoses of
      both mood (affective) disorders (32.9%) and neurotic, stress-related and
      somatoform disorders (54.7%) were common. Cognitive behaviour therapy (56.1%) was
      the most commonly used intervention followed by pharmacological therapy (25.4%).
      In conclusion, the study provides a description of the nature of the work
      encountered in a liaison psychiatry setting and demonstrates the extent of
      services provided for medical specialties within the general hospital.

PMID- 21873716
TI  - Evaluation of physician assistants in National Health Service Scotland.
AB  - Physician assistants (PAs) have medical training and work supervised by a doctor.
      In 2006-2008 the Scottish Government piloted use of USA-trained PAs. The aim of
      the paper is to evaluate the impact and contribution made by PAs to delivering
      effective health care in National Health Service (NHS) Scotland. Mixed methods,
      longitudinally, including interviews, feedback forms and activity data
      collection. Data analysis used nVivo, SPSS and Excel. Participants were 15 USA
      trained PAs, medical supervisors and team members, 20 patients, four NHS senior
      managers and three trade union representatives. Settings were four Scottish NHS
      Boards where PAs worked in primary care, out of hours clinics, emergency
      medicine, intermediate care and orthopaedics. Two minor patient safety issues
      arose. Patients were satisfied with PAs. Scope of practice did not replicate US
      working. Inability to prescribe was a hindrance. PAs tended to have longer
      consultations, but provided continuity and an educational resource. They were
      assessed to be mid-level practitioners approximating to nurse practitioner or
      generalist doctor. Valued features were generalism, medical background,
      confidence differential diagnosis and communication. Interviewees suggested PAs
      could fulfil roles currently filled by medical staff, potentially saving
      resources. In conclusion, there is potential for PAs to fulfil distinctive mid
      level roles in the Scottish NHS adding value in continuity, communication and
      medical approach.

PMID- 21873717
TI  - The relationship between body mass index and number of days spent in hospital in
      Scotland.
AB  - In most countries in the Western world, more than 50% of adults are overweight or
      obese putting them at increased risk of hypertension, type 2 diabetes, coronary
      heart disease, stroke and other chronic disorders. It is not clear what impact
      increasing prevalence of over-weight and obesity has on hospital admissions. The
      objective of this study was to examine the relationship between body mass index
      (BMI) and number of days spent in hospital. The study was designed as a
      retrospective and prospective cohort study using nationally representative Health
      Survey data linked to NHS hospital admissions data. The study was set in
      Scotland. The participants were a nationally representative sample of 6968 (45%)
      men and 8700 (55%) women, of 16-74 years of age, living in private households
      whose BMI was recorded in the 1995 and 1998 Scottish Health Surveys. The outcome
      measure was the number of days spent in hospital between 1981 and 2004. The
      results showed that the proportion of participants in both normal weight (BMI 20
      24.9 kg/m(2)) and over-weight (BMI 25-29.9 kg/m(2)) categories was 37%, with 21%
      in the obese (BMI >=30 kg/m(2)) and 5% in the under-weight (BMI <20 kg/m(2))
      categories. The median number of days spent in hospital between 1981 and 2004 was
      six. The odds ratios (95% confidence intervals) for spending above the median
      numbers of days in hospital adjusted for age, sex, socioeconomic status and
      behavioural factors (i.e. smoking, alcohol drinking and physical activity) were
      1.29 (1.06-1.56) for the <20 kg/m(2) group, 1.00 (0.91-1.11) for the 25-29.9
      kg/m(2) group and 1.24 (1.10-1.38) for the >=30 kg/m(2) group compared with the
      20-24.9 kg/m(2) group. In conclusion, extremes of BMI category identified at a
      single point in time are associated with spending above the median number of days
      in hospital over a 20-year period after adjusting for demographic, behavioural
      and socioeconomic exposures.

PMID- 21873718
TI  - National clinical portal programme: what information do doctors want?
AB  - Electronic patient health information in secondary care is often stored on
      different IT systems and not accessible to doctors involved in clinical decision
      making. The Scottish Government will support clinical portal implementation in
      all Scottish Health Boards, which will present information from different sources
      as a virtual electronic patient record. An online survey was developed and sent
      to secondary care doctors, who were asked to rank the importance of different
      types of patient-centred information, knowledge support sources, and information
      to support appraisal and continued professional development that a clinical
      portal could deliver. Subgroup analysis was performed to investigate whether
      expectations differed between senior clinicians and doctors in training. Replies
      were received from 677 senior doctors and 137 trainees. Patient-centric
      information such as current medication and allergies, clinical alerts, past
      medical history, diagnostic test results and clinical letters were ranked as most
      important. Doctors would also like access to knowledge support, such as clinical
      guidelines. Eighteen of the top 20 ranked information types were consistent
      between senior doctors and those in training grades. In conclusion, senior
      doctors and trainees consistently want to see similar information in the clinical
      portal which is largely patient-centred with some provision for knowledge
      support.

PMID- 21873719
TI  - The effect of short messaging service text on non-attendance in a general
      ophthalmology clinic.
AB  - To our knowledge there have been no previous studies that have examined the
      effect of short messaging service (SMS) text messaging reminders to both mobile
      and landlines on the 'did not attend' (DNA) rate in adult hospital clinic
      attendees. Our aim was to determine the effectiveness of a text messaging
      reminder in improving attendance in return general ophthalmology clinic patients.
      Ophthalmology clinic patients requiring a follow-up appointment were invited to
      enter the study. An information leaflet was provided and patients were contacted
      two weeks before their scheduled appointment by way of a customized text message
      to either the mobile phone or landline. The non-attendance rate compared with
      historic non-attendance rate was recorded. Two hundred and one patients were
      recruited. The historic DNA rate was 12%. The DNA rate in the SMS text reminder
      group was reduced to 5.5% (11 patients). The historic 'Could not attend' (CNA)
      rate of 6% had been reduced to 2% (4 patients). Forty-seven percent of patients
      used mobile phone technology with text messaging capability and 69% responded to
      the text reminder. In conclusion, routine SMS texting is a cost-effective means
      of reducing DNAs and should become standard practice. In addition, two-way
      messaging could allow for further efficiency as advance notification of patient
      cancellations facilitates re-scheduling of alternative patients.

PMID- 21873720
TI  - A national approach to diabetes foot risk stratification and foot care.
AB  - The Scottish Diabetes Foot Action Group (SDG) has developed and introduced a
      national strategy plan for diabetic foot care across Scotland. This has involved
      the implementation of an evidence-based national foot screening and risk
      stratification programme that has already covered 61% of the population in just
      the first two years. Nationally agreed patient information foot leaflets and
      professional education material have been introduced, and a consensus for
      antibiotic use in the diabetic foot has been published. Information on
      multidisciplinary specialist foot services has been collected, indicating that
      58% of Health Board areas have consultants with dedicated sessions in their job
      plan to a foot clinic, and 42% had integrated orthotic involvement. The SDG aims
      to increase these figures. Work has been undertaken to support local podiatry
      networks and improve communication between the specialist centre and the
      community. At a national level the SDG is working with Foot in Diabetes UK (FDUK)
      to recognize key podiatry skills by developing core competencies and a competency
      framework for the diabetes podiatrist and diabetes orthotist. The annual Scottish
      Diabetes Survey indicates some improvement in amputation rates with prevalence
      decreasing from 0.8% to 0.5%, and improved recording of foot ulceration at a
      national level. This national strategy has helped highlight the importance and
      difficulties facing diabetes foot care and should help to continue to improve the
      quality of care of people with diabetes who have foot-related problems.

PMID- 21873721
TI  - The surgical treatment of knee stiffness following anterior cruciate ligament
      reconstruction.
AB  - Knee stiffness following anterior cruciate ligament (ACL) reconstruction remains
      a common complication, which can substantially impair knee function. The aim of
      this study was to assess the effectiveness of arthroscopic arthrolysis, in
      conjunction with manipulation under anaesthetic (MUA), in treating stiffness post
      ACL reconstruction. We reviewed the records of 18 patients who underwent
      arthroscopic arthrolysis to treat established stiffness following primary
      isolated ACL reconstruction. Eight of these patients underwent concomitant MUA at
      time of arthrolysis. The median time between reconstruction and arthrolysis was
      nine months. Seven patients had arthrolysis performed within eight months of
      reconstruction, while 11 patients underwent arthrolysis greater than eight months
      postreconstruction. Following arthrolysis, the mean extension loss improved from
      7 degrees  to 1 degrees . In patients with mild extension stiffness
      (prearthrolysis extension deficits <10 degrees ), the mean improvement to
      extension was 3 degrees . In patients with severe extension stiffness
      (prearthrolysis extension deficit >=10 degrees ), the mean improvement to
      extension was 10 degrees . Arthroscopic arthrolysis was significantly more
      effective in restoring extension loss if carried out within eight months of the
      primary reconstruction (P < 0.03). In the patients who underwent MUA at time of
      arthrolysis, the mean flexion loss improved from 16 degrees  to 4 degrees . In
      conclusion, arthroscopic arthrolysis, in conjunction with MUA, is an effective
      treatment for knee stiffness post-ACL reconstruction but ideally should be
      carried out within eight months.

PMID- 21873722
TI  - Ratfish (Chimaera) spine injuries in fishermen.
AB  - An occupational hazard peculiar to fishermen, is an injury from a sharp fish
      spine. Such spines can cause envenomation injury, infectious sequelae or trauma
      to anatomical structures. The management of two fishermen with penetrating
      ratfish (Chimaera) spine injuries to the lower limb is described. Both were
      managed by removal of the spine under general anaesthesia. In the second patient,
      the spine was embedded adjacent to the left femoral artery, highlighting the
      potential for major haemorrhage and supporting the use of surgical wound
      exploration when important structures may be involved. Herein, we describe the
      first report in English of Chimaera spine injury. In addition, we surveyed nine
      northeast Atlantic deep-sea fishermen to gain information on exposure to, and
      injuries from, this type of fish. The most commonly identified species was
      Chimaera monstrosa. Five fishermen reported injuries to their feet or hands from
      Chimaera spines and two had sought medical attention. The evidence indicates that
      deep-sea trawler fishermen of the northeast Atlantic frequently encounter
      Chimaera species and can suffer dangerous penetrating wounds from its dorsal
      spine.

PMID- 21873723
TI  - A peculiar Scottish disorder.
AB  - A highly contagious behavioural affliction is now endemic in highland areas of
      Scotland. Pretravel advice ought to include a health warning to sport-lovers
      venturing north into wild, highlands of Gaeldom. It particularly affects young
      adults and predominates in men, although women are affected. The disorder can be
      acute or chronic and when severe, it can threaten one's life and limbs. Acute
      attacks may bring spontaneous recovery in months, but the chronic state can last
      for a life-time. Death will overtake some before it runs its inevitable course.

PMID- 21873724
TI  - Upper gastrointestinal bleeding: what's the score?
AB  - Upper gastrointestinal haemorrhage (UGIH) is a common medical emergency. Recent
      publications have emphasised the need for early risk assessment of patients with
      this condition to help direct management. Several risk scores have been developed
      for UGIH and are variably used in clinical practice. In this article, we discuss
      the various risk scoring systems for this condition and summarise the available
      evidence for their use.

PMID- 21873725
TI  - Old herbal remedies and modern combination therapy.
AB  - The use of herbs as cures for human ailments is as old as modern man, but has now
      been replaced by synthetic drugs. However, the mixture of bioactive substances
      found in many traditional herbal remedies has similarities with modern
      combination therapies, like those developed by Sir John Crofton in Edinburgh for
      the treatment of tuberculosis. It is suggested that, in the development of these
      therapies, it might be possible to learn from the drug 'cocktails' found in
      plants.

PMID- 21873726
TI  - Painless arm swelling.
AB  - A case report of a patient presenting with painless arm swelling, which provides
      diagnostic challenge and interesting imaging on the conditions of syringomyelia
      and neuropathic osteoarthropathy, conditions with distinguishing clinical
      features and disabling consequences if misdiagnosed.

PMID- 21873727
TI  - Dental hyponatraemia.
AB  - A 14-year-old girl developed dental pain and was treated for acute infected
      pulpitis of her right upper lateral incisor with drilling and filling. The pain
      continued and was helped by analgesia, sucking ice cubes and drinking cold water.
      Forty-eight hours later, she became confused and disoriented. She started to
      vomit and complained of headache. Investigations revealed hyponatraemia with
      normal serum potassium levels and initially normal urinary sodium excretion. Over
      the next 24 hours, she passed 5.45 L of urine and her serum sodium rose from 125
      to 143 mmol/L. Self-induced water intoxication has been described during drinking
      games and initiation ceremonies, but this would appear to an unusual cause.
      Conservative management proved successful in allowing this girl to recover
      without sequelae.

PMID- 21873728
TI  - Synchronous colonic adenocarcinoma and renal oncocytoma: a case report and
      literature review.
AB  - We present the case of a patient with an adenocarcinoma of the colon associated
      with an oncocytoma of the kidney. A left colonic cancer was diagnosed at
      colonoscopy and an incidental finding of a left renal mass was noted, with a
      staging computerized tomography scan. Following a left hemicolectomy and a left
      nephrectomy, the pathological report confirmed the presence of a colonic
      adenocarcinoma and revealed that the left renal mass was an oncocytoma. This case
      report reviews the management decisions associated with incidental renal masses
      as well as the treatment of synchronous neoplasia.

PMID- 21873729
TI  - Abnormal activated partial thromboplastin time and malignancy.
AB  - Malignancy often results in clotting abnormalities. The aetiology of haemostasis
      problems in cancer is complex, and is still not completely understood. We
      describe a case of a patient with malignant mesothelioma, who was found to have
      elevated activated partial thromboplastin time, due to lupus anticoagulant. We
      suggest that patients with malignancy should have their coagulation checked prior
      to any invasive procedures.

PMID- 21873730
TI  - Distal embolization from medial cystic degeneration of the popliteal artery.
AB  - This is the first reported case of medial cystic degeneration of the popliteal
      artery presenting as distal embolization and contains a high-definition photo of
      the cyst in situ. Duplex ultrasound and magnetic resonance angiography are useful
      adjuncts to diagnosis. Based on the published literature, resection and
      interposition grafting appears to be the most efficacious treatment modality.

PMID- 21873731
TI  - A rare case of ovarian carcinoid causing heart failure.
AB  - Carcinoid tumours are rare tumours of the neuro-endocrine system. They most
      commonly present in the gut; however, they can present in other organs. In all,
      0.3% of carcinoid tumours are ovarian in origin. Subsequently, very few cases of
      ovarian carcinoid affecting the heart have been reported and this case adds to
      the literature on this. There are very few reports in the literature of ovarian
      carcinoid and even fewer on cardiac failure due to carcinoid. Generally,
      carcinoid heart disease only affects the right-sided valves, sparing the mitral
      and aortic valves. We present the case of a patient who had an ovarian carcinoid
      tumour excised successfully and had been asymptomatic for 14 years prior to an
      incidental finding of right valvular signs on echocardiography, before
      subsequently right heart failure deemed to be secondary to ovarian carcinoid
      heart disease. The diagnosis is generally made on the findings of right-sided
      heart failure and the valvular abnormalities on echocardiogram (isolated
      pulmonary and tricuspid involvement). If the tumour is present at the same time
      as the development of heart failure, cardiac function can improve with timely
      tumour resection; however, cardiac disease can occur despite tumour removal.

PMID- 21873732
TI  - A trout fisherman with hypercalcaemia and skin lesions.
AB  - A 67-year-old trout fisherman presented with a six-week history of polyuria,
      polydipsia, dyspnoea on exertion and the development of subcutaneous extensor
      surface skin nodules. He was hypercalcaemic with acute renal impairment.
      Parathyroid hormone was suppressed and vitamin D levels were within normal
      limits. The patient had a past history of hypothyroidism, but thyroid replacement
      was adequate. Hypoadrenalism, myeloma and metastatic malignancy were excluded.
      Biopsy of a subcutaneous nodule revealed dermally based non-caseating
      granulomata, consistent with sarcoidosis. Serum angiotensin-converting enzyme was
      elevated, and computerized tomography scanning of the chest and abdomen revealed
      widespread lymphadenopathy with multiple lung nodules and splenomegaly.
      Prednisolone therapy produced rapid resolution of his skin lesions and
      normalization of his bone and renal biochemistry. The mechanism of hypercalcaemia
      in sarcoidosis is poorly understood but is thought to involve parathyroid hormone
      independent 1-hydroxylation of 25-hydroxyvitamin D within sarcoid lesions. This
      process may be exacerbated by exposure to UV light and it is of interest that
      this patient developed symptoms after a period of intense trout fishing in the
      good weather of April and May 2007.

PMID- 21873734
TI  - The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by
      downregulating Wnt signalling.
AB  - AIMS: Wnt signalling is involved in cellular homeostasis and development.
      Dysregulation of the Wnt signalling pathway has been linked to colorectal cancer.
      The orphan nuclear receptor TR3 plays important roles in proliferation and
      apoptosis. In this study, we investigated how TR3 suppresses intestinal
      tumorigenesis by regulating Wnt signalling. METHODS: Intestinal polyps were
      quantified in Apc(min/+), Apc(min/+)/TR3(-/-) and Apc(min/+)/villin-TR3 mice. Wnt
      signalling activity was evaluated by assessing beta-galactosidase activity in a
      BAT-Gal reporter strain. The TR3 agonist cytosporone B was used to evaluate the
      role of TR3 in intestinal tumorigenesis. Crosstalk between TR3 and beta
      catenin/TCF4 was analysed by molecular methods in colorectal cancer cells. The
      phosphorylation of TR3 by glycogen synthase kinase (GSK) 3beta and the
      correlation between GSK3beta activity and TR3 phosphorylation were evaluated in
      clinical samples and colorectal cancer cells. RESULTS: TR3 was found to
      significantly suppress Wnt signalling activity and the proliferation of
      intestinal epithelial cells. Apc(min/+)/TR3(-/-) mice developed more intestinal
      polyps than Apc(min/+)/TR3(+/+) mice, whereas either transgenic overexpression of
      TR3 in the intestine or treatment with cytosporone B in Apc(min/+) mice
      significantly decreased intestinal tumour number. Mechanistically, TR3 disrupted
      the association of beta-catenin and TCF4 on chromatin and facilitated the
      recruitment of transcriptional co-repressors to the promoters of Wnt signalling
      target genes. However, TR3 was phosphorylated by GSK3beta in most clinical
      colorectal cancers, which attenuated the inhibitory activity of TR3 towards Wnt
      signalling. CONCLUSIONS: TR3 is a negative regulator of Wnt signalling and thus
      significantly suppresses intestinal tumorigenesis in Apc(min/+) mice. This
      inhibitory effect of TR3 may be paradoxically overcome through phosphorylation by
      GSK3beta in clinical colorectal cancers.

PMID- 21873735
TI  - Stem cell markers characterise familial adenomatous polyposis.

PMID- 21873736
TI  - T cell responses in hepatitis C: the good, the bad and the unconventional.
AB  - Over recent years, it has become increasingly accepted that virus-specific CD4+
      and CD8+ T cell responses play a major role in outcome and pathogenesis of
      hepatitis C virus (HCV) infection. Indeed, while the emergence of strong and
      multispecific T cell responses may correlate with spontaneous viral clearance,
      the virus has developed several mechanisms to avoid T cell control in the
      majority of acutely HCV-infected patients that subsequently develop persistent
      HCV infection. In this review, we will discuss the current knowledge about the
      role of cellular immune responses in HCV infection. Specifically, we will
      emphasise recent new insights into the effector functions of T cells, possible
      mechanisms of their failure and the host-virus interactions occurring at the site
      of the disease, the liver.

PMID- 21873738
TI  - [Therapeutic strategy against gliomas based on their molecular biological
      nature].

PMID- 21873737
TI  - Mechanism of association between BMI and dysfunction of the gastro-oesophageal
      barrier in patients with normal endoscopy.
AB  - INTRODUCTION: The association between body mass index (BMI) and gastro
      oesophageal pressure gradient (GOPG) is incompletely understood. We examined the
      association between BMI and gastro-oesophageal (GO) barrier function and the
      effect of mechanically increasing intra-abdominal pressure on GO physiology.
      METHODS: (A) 103 dyspeptic patients with normal endoscopy underwent 24 h pH-metry
      and upper gastrointestinal manometry. Relationships between BMI and acid reflux,
      intragastric pressure (IGP), GOPG and lower oesophageal sphincter (LOS) pressure
      were calculated using bivariate correlations. (B) In 18 healthy volunteers, the
      effects of increasing IGP by abdominal belt on GO manometry were studied.
      RESULTS: (A) There was a linear correlation between BMI and oesophageal acid
      exposure in erect (R=0.35, p<0.001) and supine (R=0.40, p<0.001) positions. BMI
      was strongly associated with IGP (inspiration: R=0.66, p<0.001; expiration:
      R=0.78, p<0.001) and inspiratory GOPG (R=0.50, p<0.001). There were a positive
      correlation between BMI and inspiratory LOS pressure relative to atmospheric
      pressure (R=0.29, p=0.016) and a negative correlation with LOS pressure relative
      to IGP on expiration (R=-0.25, p=0.018). Logistic regression models using all
      significant manometric variables and relevant interactions revealed marked
      decline in the magnitude and significance of relationship between BMI and
      oesophageal acid exposure in supine (from OR 1.12 (95% CI 1.03 to 1.22), p=0.009,
      to 1.00 (0.86 to 1.17), p=0.999) and upright positions (from 1.11 (1.02 to 1.20),
      p=0.020, to 1.03 (0.89 to 1.18), p=0.717). (B) Application of the constricting
      abdominal belt produced similar manometric changes to those associated with
      increased BMI. However, the belt did not reproduce the reduced LOS pressure
      relative to IGP. CONCLUSION: The association between reflux and BMI may be
      largely explained by effects of increased intra-abdominal pressure. However, the
      reduced LOS pressure associated with BMI may be mediated by another mechanism or
      effects of chronic rather than acute elevation of intra-abdominal pressure.

PMID- 21873739
TI  - [Surgical approach for craniopharyngioma bifrontal basal interhemispheric
      approach/extended endonasal endoscopic approach].

PMID- 21873740
TI  - [A case of meningeal melanocytoma in the cerebellopontine angle].
AB  - Meningeal melanocytomas are uncommon intracranial tumors and extremely rare in
      the cerebellopontine angle (CPA). The tumors are generally considered to be
      benign because they lack malignant features in histological examination, but
      several literatures describe malignant behavior of the tumors such as high
      frequency of local recurrence, malignant transformation with leptomeningeal
      seeding. We describe a case of meningeal melanocytoma in the CPA and discuss the
      features of the tumor. The case was a 43-year-old woman with a right CPA exta
      axial mass suffering from vertigo and nausea. Computed tomography (CT) and
      magnetic resonance imaging (MRI) showed a mass in the right CPA. The mass was
      hyperintense on T1-weighted images and hypointense on T2-weighted images.
      Surgical removal was done and pathological diagnosis was made as meningeal
      melanocytoma. Twenty months after the first surgery, MRI revealed local
      recurrence of the tumor and subtotal resection was performed.

PMID- 21873741
TI  - [Pilocytic astrocytoma of the cerebrum presenting in an elderly patient: a case
      report].
AB  - We report a case of pilocytic astrocytoma of the cerebrum presenting in an
      elderly patient. A 76-year-old man was admitted to our department due to the
      development of dysarthria. MRI showed a cystic mass with an enhanced small mural
      nodule in the left frontal lobe. At surgery, the cyst contents were aspirated,
      and the mural nodule was excised. Histological examination showed a pattern that
      is usually seen in pilocytic astrocytoma of the cerebellum, including loose and
      compact areas composed of pilocytic and stellate cells, a few eosinophilic
      granular bodies, but not Rosenthal fibers. Pilocytic astrocytoma is a common type
      of pediatric brain tumor that can arise within either the cerebellum or the
      hypothalamic/chiasmatic region, but rarely seen in the cerebral hemisphere at an
      advanced age. To our knowledge, only 45 cases of pilocytic astrocytoma of the
      cerebrum developing in an adult are reported. In those cases, the symptoms of the
      disease developed during the third decade of life. The onset at a most advanced
      age as in the present case is thought to be extremely rare.

PMID- 21873742
TI  - [Concomitant intracerebral hemorrhage and cerebral infarction in moyamoya
      disease: a case report].
AB  - We encountered a case of moyamoya disease which exhibited intracerebral
      hemorrhage with intraventricular hemorrhage followed by cerebral infarction in a
      short time. A 39-year-old female presenting with sudden onset disturbance of
      consciousness was admitted to our hospital. Radiological investigation on
      admission revealed intracerebral hemorrhage in the left temporal lobe and
      intraventricular hemorrhage due to moyamoya disease. The patient experienced
      cerebral infarction of the left frontotemporal area with brain swelling after 20
      hours had passed. In spite of immediate left frontotemporal craniectomy and
      evacuation of the hematoma, she died 9 days after the operation. This case
      indicates that adequate control of intracranial pressure such as ventricular
      drainage is important to prevent progression of ischemic attack at an early
      stage. But it is not known what case of cerebral hemorrhage due to moyamoya
      disease would be complicated by cerebral infarction. The detection of the
      patient's consciousness level at an early stage could be a landmark to prevent
      further ischemic complications.

PMID- 21873743
TI  - [Cystic meningioma originating from cavernous sinus: a case report].
AB  - A 72-year-old man presented with gait disturbance and right homonymous
      hemianopsia. Magnetic resonance (MR) imaging showed a solid mass around the left
      cavernous sinus with rostral development of a multi-lobulated cystic component.
      The tumor was totally removed including the cystic wall via the left transsylvian
      approach with orbito-zygomatic craniotomy. Most of the tumor was attached to the
      lateral wall of the left cavernous sinus. Histological examination showed a
      meningioma WHO grade I with meningothelial meningioma formed lobules with
      intranuclear inclusions. His neurological symptoms disappeared immediately after
      the operation. Postoperative MR imaging revealed total removal of the tumor
      including the large cystic component.

PMID- 21873744
TI  - [Primary central nervous system lymphomatoid granulomatosis: a case report].
AB  - Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated
      multisystem lymphoproliferative and granulomatous disease histologically
      characterized by angiocentric and angiodestructive cellular infiltrate. LYG
      usually involves the lungs, skin, kidneys and brain, but isolated central nervous
      system LYG has been reported rarely. We describe a 57-year-old man with
      histologically proved LYG confined to the brain. The patient complained of visual
      disturbance, and was admitted to our hospital. Gadolinium-enhanced T1-weighted
      MRI showed irregular, partly cystic and lobulated enhancement in the left
      occipital lobe, suggesting the presence of possible neoplastic lesions such as
      glioma, malignant lymphoma or metastatic brain tumor. We performed surgical
      resection of the lesion. Histological and immunohistochemical examinations of the
      tumor showed angiocentric polymorphic infiltration and granulomatous reaction,
      consisting of CD3-positive small lymphocytes and CD20-positive large atypical
      cells. Subsequently, in situ hybridization study for EBER (Epstein-Barr virus
      encoded small RNA) was performed and proved that the large atypical cells were
      positive for EBER. These findings were compatible with LYG. We emphasize that the
      possibility of LYG should be considered in the differential diagnosis of any ring
      like enhancing mass lesions on MR images, though less specific for LYG.
      Histopathological examination is indispensable for the final diagnosis and the
      choice of an optimal treatment strategy.

PMID- 21873745
TI  - [Treatment of unruptured saccular vertebral artery aneurysm for preservation of
      the parent artery for advanced age people: a case report].
AB  - A 79-year-old female was referred to our hospital presenting with occipital
      headache. Her unruptured aneurysm was incidentally found by magnetic resonance
      angiography. Three dimensional computed tomographic angiography showed a saccular
      aneurysm located at the junction of the left vertebral artery (VA) and posterior
      inferior cerebellar artery (PICA) that originated from the aneurysm itself.
      Firstly, surgical clipping of the left PICA just distal to the aneurysm and
      occipital artery (OA)-PICA bypass was carried out and, secondly, endovascular
      treatment was performed for preservation of the parent artery.

PMID- 21873746
TI  - [Congenital anomalies in the central nervous system(10) spinal lipoma].

PMID- 21873747
TI  - Concepts of neurodevelopment in sports activity for adolescents.
AB  - This article highlights comments on this question for both teenager and parent,
      focusing on key underlying concepts as neurodevelopment and sports readiness.
      Issues regarding neurodevelopment in adolescent sports are considered in this
      article. Understanding the neurodevelopment of the Adolescent Athlete and how
      this development impacts sports participation is critical for clinicians to
      provide parents, coaches, and sports organizers with valuable information about
      how to select activities for their children that will have a positive impact on
      their overall growth and development as well as optimize their benefit from
      sports play. Stories of child prodigies who began to learn a specific sport
      before age three stimulate parents to question whether or not they also should be
      enrolling their very young children in such aggressive training programs.
      Physicians and health care sports professionals should provide information to
      other professionals and parents about issues related to successful sports
      participation of the pediatric athlete, both as a child and as an adolescent.

PMID- 21873748
TI  - Assessment of anthropological, physical and functional indices in sportsmen
      (basketball players) against the background of high physical loading.
AB  - The goal of the investigation was the estimation of functional condition of
      anthropometrical, physical and cardiovascular system of sportsmen-basketball
      players against the background of high physical loading. 100 basketball players
      at the age from 12 till 18 years underlay the study. Randomized and open
      controllable research was carried out during 6 months. The following
      characteristics have been studied: how many days the sportsman is training in a
      week, how many hours the sportsman is training per day, his mood after training,
      over fatigue and overtension, frequency of heartbeat, time of breath holding, the
      general condition, the height in sitting and standing position; circumference of
      lumbus, chest, arm and limbs, the pulse, pulse, systolic and diastolic arterial
      pressure before and after physical loading. According to these factors the
      following sport indices are calculated: Index of Rufe (physical work capacity),
      the coefficient of endurance (Kvas formula), Shtange test (breath holding at
      sighing), Genchi test (breath holding at exhalation), average arterial pressure,
      systolic and cardiac output of blood circulation (the formula of Lilienstrad and
      Tsander), the coefficient of blood circulation effectiveness, Ketle index (the
      ratio of height and weight), Minuvre index (the ratio of body and feet length),
      Pinie index (power of body-build). Statistically authentic increase of breath and
      pulse in frequency was observed in sportsmen-basketball players after physical
      loading. The study of amplitude parameters of cardiac cycle among sportsmen
      basketball players before and after physical loading has revealed the ability of
      rather low adaptation of cardiovascular system to physical loading.

PMID- 21873749
TI  - Body composition and physical capacity of elite adolescent female tennis players.
AB  - The study was performed to evaluate relationships among the major anthropological
      parameters: (body mass - BM, height, body mass index - BMI, lean body mass - FFM,
      proportion of fat mass -Fat%), physical capacity, and the tennis federations
      ranking position as an index of the temporal sport success. Seventeen elite
      female tennis players, divided into three age-matched groups (15, 16, and 17 yr)
      participated in this study. All the players had a national singles ranking
      (positions between 1st-80th) and in International Tennis Federation's Junior
      Circuit ranking (ITFJC; 21st to 990th position of ITF). Body composition was
      assessed via bioelectrical impedance. Maximal aerobic capacity (VO2max) was
      calculated from the distance covered in 12-min run test via Cooper's formula.
      Wingate test with lactate assay was used as an index of anaerobic capacity. There
      was a significant age-related trend for an increase in BM, height, FFT, and Fat%,
      associated with impressive shift of the anthropological indexes of body weight
      and height, assessed by the percentile chart analysis. The unexpected body growth
      spurt evidently observed between aged 15 and 17 is supposed to reflect a delay in
      somatic development, related to extensive exercise load. Body composition did not
      correlate to the ranking positions. All tested tennis players revealed excellent
      aerobic capacity associated with poor indices of anaerobic fitness. The position
      in the tennis federations rankings correlated to VO2max but not with maximal
      power or maximal work output assessed by Wingate test. In the whole group the
      maximal power and work output were proportional to BMI and FFM, but not to Fat%.
      In conclusion, in light of the contradictory reports concerning a possible link
      between strenuous regular exercise performed by young children and adolescent
      elite sportsmen our data indicate a delayed growth spurt in the elite female
      tennis players to occur between ages 15 and 17. The other important finding in
      terms of prospective for future professional career is the evident link between
      aerobic capacity and ranking positions.

PMID- 21873750
TI  - Variable profile of individual heart rate responses to cold water immersion apnea
      in healthy late adolescent men.
AB  - Holding breath combined with immersion of face in cool water induces diving
      reflex consisting in bradycardia, peripheral vasoconstriction, and preferential
      redistribution of blood to the vital organs. The individual responses are
      variable, highly expressed in young children to weaken with age. Detailed
      assessment of the cardiac response to diving in late adolescents who are mostly
      prone to unexpected diving experiments and related complications are of practical
      importance. The study was performed to the investigate the heart rate (HR)
      response to controlled breath-hold diving in cold water in young healthy late
      adolescents aged 17.5 - 20.4. Twenty volunteers performed a procedure consisting
      in immersion of face in cold water during possibly long breath-holding. Beat-to
      beat HR was assessed from the continuous ECG recording. Average diving time (tD)
      was 77.5+/-10.5 s, ranging from 61.7 to 95.4 s. Apnea and face immersion induced
      a biphasic response: an increase in HR was followed by its gradual decrease to
      reach a final limit of the response 47.7+/-9.0 beats/min at 55.2+/-16.1 s of
      dive. Within a variable time course of the evoked responses, two patterns of the
      HR decrease were distinguished: monoexponential decay functions fitted best for 8
      (40%) subjects with a constant rate tau 31.3+/-11.4 s-1, whereas the 60% majority
      displayed a two phase negative chronotropic effect with constant rates: tau1
      10.3+/-4.2 s-1 and tau1 25.5+/-10.1 s-1. The initial, anticipatory excitation
      influenced the HR response: the higher was the initial HR increase, the more
      pronounced was bradycardia. Disturbances of heart rhythm were observed in
      majority of subjects: supraventricular ectopic beats (40%), ventricular beats
      (20%), I-degree AV block (30%), II-degree Mobitz I block (15%), junctional rhythm
      (60%). In one case pair of ventricular ectopic beats looked severe and the trial
      was rapidly terminated. In conclusion, the unquestionable potency of late
      adolescents towards diving challenges, accompanied with a vigorous emotionally
      driven initial cardioexcitation meets a relevant vulnerability for arrhythmias.

PMID- 21873751
TI  - [Characteristics of heart rate variability in healthy adolescents and male
      adults].
AB  - The primary purpose of the present article is to investigate the comparative
      characteristics of heart rate variability in healthy adolescents and male adults.
      The study was carried out on 41 male adolescents aged 15-16 years and 73 male
      adults aged 18-22 years. For assessment of heart rate variability statistical
      data of variability and spectral analysis of heart rate were estimated. Achieved
      results have proved once again that vegetative balance in healthy individuals is
      not identical that can be explained by various physiological processes of
      adolescent age. Such start conditions probably may affect the character of body
      response to different stimulative impacts. The study suggests that adults tend to
      have the prevalence of sympatic regular mechanisms whereas in mature age the
      cases of individuals with the balanced vegetative nervous system in quiescent
      mode without pathologies are much more frequent.

PMID- 21873752
TI  - Advocating an agentic and potentialist view to health psychology.
AB  - The article covers the notions of agency and potentials, social cognitive theory
      (SCT), their definition and importance for the health. These two notions are
      crucial for reorienting psychological investigations and interventions in
      accordance with new findings about human personality and the new demands of
      society. The notion of agency points to the fact that people may actively
      contribute to the full expression of their natural and social endowments, the
      notion of potentials highlights the fact that much of human strengths derive from
      people discovering and nurturing their capacities while acknowledging
      environmental opportunities. A basic goal of agentic and potentialist views is to
      shed light on the psychological systems that enable people to regulate their
      experiences and actions and thus to contribute to the development of their
      potentials. In this regard a large body of research attest to the merits of
      social cognitive theory (SCT) in providing a firm basis for guiding research and
      designing psychosocial interventions aimed at maximizing individuals' functioning
      and well being. SCT focuses on the unique properties of human agency that allow
      people to reflect on their capabilities for action and to accord their conduct to
      the pursuit of outcomes they value, and points to structures and processes which
      enable people to guide behaviour purposively and to chart the course of their
      life. Social cognitive theory and practice provide unique directions to identify
      the strategies more suitable to promote individual flourishing by enabling people
      to make choices and to engage in pursuits that mostly serve to their growth,
      health and well-being.

PMID- 21873753
TI  - [Psychophysiological structure of verbal and nonverbal intellect in 6-7 year old
      children with attention-deficit hyperactivity disorder].
AB  - Wechsler test revealed the peculiarities of intellectual development of children
      with Attention-Deficit Hyperactivity Disorder (ADHD). It is shown that the
      psychophysiological structure of intelligence in 6-7 year old children without
      any signs of ADHD is characterized by a high level of development and close
      interaction between verbal and nonverbal components. Their peers with ADHD
      demonstrate an insufficient level of development of visual-spatial perception,
      voluntary activity organization and regulation, and a lower level of interaction
      between verbal and nonverbal components. Significant differences between verbal
      and nonverbal integral indices are the evidence of the deficit in voluntary
      attention and voluntary regulation and in the integrity of operational cognitive
      structures.

PMID- 21873754
TI  - [Blood biochemical changes in maternally deprived children and their emotional
      status].
AB  - Environmental rearing conditions during the neonatal period are critical for the
      establishment of neurobiological factors controlling behavior and stress
      responsiveness. Early maternal deprivation in animals consisting of a single 24-h
      maternal deprivation episode during early neonatal life has been proposed as an
      animal model for certain psychopathologies including anxiety, depression and
      schizophrenic-related disorders. The aim of the present research was to show the
      mechanisms how the early maternal deprivation in humans influences the emotional
      status of children. To understand the effects of early deprivation on the
      regulation of the hypothalamic-pituitary-adrenal axis of children following
      social interactions, we examined the blood neurotransmitters levels (Norepinefrin
      NA; Dofamin DF; Serotonin SE) in a group of healthy institutionalized children at
      age from 6 to 36 months from Tbilisi Infant's House. A group of healthy children
      of the same age from Mother & child shelters formed the control group. Emotional
      status was assessed by Leusher's Color Test in a group of healthy
      institutionalized children at age from 3 to 6 years from Tskneti Orphanage.
      Institutionalized children showed elevations in blood NE and decreased SE and DF
      concentrations in comparison with non deprived children's blood. The higher was
      percentage of children with high level of anxiety in the group of children from
      orphanage than in the children with family care. The results suggest that early
      maternal deprivation may contribute to long-term regulatory problems of the
      stress-responsive system that may be resulted in altered emotionality and
      behavior in deprived children.

PMID- 21873755
TI  - Diagnostics and management of sleep-related respiratory disturbances in children
      with skeletal dysplasia caused by FGFR3 mutations (achondroplasia and
      hypochondroplasia).
AB  - To evaluate the frequency of clinical indicators for sleep-related respiratory
      disturbances (SRD) and the polysomnographical manifestations of these disorders
      in children with skeletal dysplasia caused by FGFR3 mutations. From January 1990
      to January 2009, 24 patients (22 achondroplasia, 2 hypochondroplasia; 13 boys, 11
      girls; age 8 days to 15 years, median age 3.0 years) were examined, including a
      semi-structured interview, a clinical examination, and a polysomnographic sleep
      recording (65 polysomnographic sleep recordings (PSG) in 24 patients). We
      performed PSG in a subgroup of five patients before and after adenoidectomy (AT)
      and/or tonsilectomy (TE). Daytime symptoms suggestive of SRD (daytime somnolence,
      attention and concentration problems, behavioural problems, and pallor) were
      found in 4/24 patients (16.7%). Sleep-related symptoms (snoring, mouth breathing,
      cyanosis, observed apneas, excessive sweating, enuresis, problems of initiating
      and maintaining sleep) were present in 18/24 patients (75%). Prior to the first
      PSG, 11/24 patients (45.8%) had undergone AT, 1/24 (4.2%) TE, 2/24 (8.3%)
      adenotonsilectomy (ATE), 3/24 (12.5%) liquor drainage, and 6/24 (25%) a
      craniocervical decompression operation. Clinical examination prior to PSG
      revealed hypertrophied tonsils in 11/24 patients (45.8%), disturbed nasal
      breathing in 8/24 patients (33.3), and enlarged cervical lymph nodes as a sign of
      chronic tonsillitis in 5/24 patients (20.8%). PSG findings were abnormal in 19/24
      patients (79.2%) with a nadir of oxygen saturation (pulse oximetry) below 90%
      and/or a nadir of transcutaneous partial pressure of oxygen below 45 mmHg.
      Pathologic PSG findings were found in 10/24 patients (41.7%): obstructive sleep
      apnea syndrome (OSAS) was diagnosed in 8/24 patients (33.3%), central sleep apnea
      syndrome in 1/24 patients (4.2%), and hypoventilation in 1/24 patients (4.2%). As
      a consequence, the following therapeutic interventions were performed: AT in 1/24
      patients (4.2%), TE in 2/24 (8.3%), ATE in 2/24 (8.3%), and nasal continuous
      positive airway pressure (continuous positive airway pressure) and bilevel
      positive airway pressure therapy (bilevel positive airway pressure),
      respectively, in 3/24 patients(12.5%). SRD, especially OSAS, represent a
      complication of clinical and prognostic relevance in children with
      achondroplasia. We therefore think that not only those children with a history
      suggestive of SRD, but all achondroplastic children should be evaluated by PSG.
      At least in a part of these patients, the pathophysiological mechanisms of OSAS
      are connected with the etiology of achondroplasia. Achondroplastic children with
      OSAS, who do not benefit from AT and/or TE, should be treated with NCPAP therapy.

PMID- 21873756
TI  - Managing sleep disorders in children: which is the best strategy?
AB  - This review aims to critically analyze the literature studies showing the
      effectiveness of cognitive-behavioral strategies in the treatment of sleep
      disorder during the developmental age. About 15-35% of children suffer from sleep
      disorder. If they are not treated right away, it can persist into adulthood.
      Recent studies demonstrate an effective cognitive-behavior treatment for these
      disturbances. In this regard, the most effective method seems to be extinction
      (standard, with parental presence, graduated), the bedtime routine, scheduled
      awakenings, and preventive parent education. The procedures of extinction, not
      only its effectiveness, have limited application for the difficulty that compares
      to the parents following the procedure of the intervention. They are not able to
      ignore their children when they are crying for long prolonged period of time.
      Bedtime routine is relevant in the prevention and treatment of sleep disorders.
      The scheduled awakenings are a useful technique that teaches parents to change
      the way they interact with the child's disturbed sleep, allowing recovery.
      Finally, preventive parental education depends on the parents or caregivers and
      aims to educate them; during the prenatal or postnatal period with their child's
      sleep it seems useful in preventing irregular pattern formation and temporal
      regulation of sleep. The vast majority of children's sleep disruptions seem to
      resolve only with the cognitive-behavioral intervention, while in some
      psychopathologic disruptions it is necessary to combine cognitive-behavioral and
      drug therapy. Literature reviews show that clinical research concerning sleep
      disruptions is still very limited. In current reviews, there have been diverse
      investigations on efficacy of cognitive-behavioral interventions and sleep
      disruptions, highlighting both the strong points and weak points. Therefore, this
      analysis could be a starting point for developing further research since there is
      a lack of studies in relation to evidence-based interventions and specific
      therapeutic factors for each intervention and disturbance.

PMID- 21873757
TI  - Tempo and amplitude in growth.
AB  - Growth is defined as an increase of size over time with time usually defined as
      physical time. Yet, the rigid metric of physical time is not directly relevant to
      the internal dynamics of growth. Growth is linked to maturation. Children and
      adolescents differ in the tempo at which they mature. One calendar year differs
      in its meaning in a fast maturing, and in a slow maturing child. The slow child
      needs more calendar years for completing the same stage of maturity. Many
      characteristics in the human growth curve are tempo characteristics. Tempo -
      being fast or slow maturing - has to be carefully separated from amplitude -
      being tall or short. Several characteristic phenomena such as catch-up growth
      after periods of illness and starvation are largely tempo phenomena, and do
      usually not affect the amplitude component of growth. Applying Functional Data
      Analysis and Principal Component Analysis, the two main sources of height
      variance: tempo and amplitude can statistically be separate and quantified. Tempo
      appears to be more sensitive than amplitude to nutrition, health and
      environmental stress. An appropriate analysis of growth requires disentangling
      its two major components: amplitude and tempo. The assessment of the
      developmental tempo thus is an integral part of assessing child and adolescent
      growth. Though an Internet portal is currently available to process small amounts
      of height data (www.willi-will-wachsen.com) for separately determining amplitude
      and tempo in growth, there is urgent need of better and practical solutions for
      analyzing individual growth.

PMID- 21873758
TI  - Anthropometric data peculiarities in early school children population.
AB  - The anthropometric data were studied in early school aged (6-7 years old)
      children and the degree of harmonization during physical development was
      evaluated. Representative population of 400 otherwise healthy early school aged
      children was included in study group. Study period covered the end of school
      year. In the selected under observation focused population the level of
      individual anthropometric data was determined in percentile intervals according
      its position. Anthropometric data assessments by using percentile method it was
      revealed in early school aged (6-7 years of old children) excess in body height
      and weight in comparison with normal values. This phenomenon indicates the
      prevalence of acceleration and weight gain. Anthropometric data in boys were
      increased while comparing with physical development data in girls. This result
      difference has the tendency to statistically insignificant. Physical development
      harmonization values were studied in 200 children. Harmonized physical
      development revealed in 50 children (25%); disharmonized physical development I
      50 children (15%), among them with I degree weight gain were 48 (24%), and with I
      degree weight deficit were 2 (1%). Markedly disharmonized development had 100
      children (50%), among them with II degree weight gain were 98 (49%), and with II
      degree weight deficit were 2 (1%). According to the children's anthropometric
      data and assessment by physical development harmonization percentiles tables
      three groups of children were organized: main, risk group and the group with
      deviation in physical development. On the basis of resulted data the study of
      early school age children's physical development gives possibility for risk
      groups stratification, which in turn itself makes a strong basis for reasonable
      preventive measurements and stepwise monitoring implementation.

PMID- 21873759
TI  - Evaluation of treatment effects in obese children with co-morbid medical or
      psychiatric conditions.
AB  - The need for effective treatments for pediatric overweight is well known. To
      evaluate the applicability of an evidence-based treatment in an applied clinic
      setting that includes children with severe obesity and comorbid medical or
      psychiatric conditions. Forty-eight overweight children and their families were
      provided an evidence-based intervention at a for-profit clinic. Unlike typical
      lab-based samples, participants were self-selected and included children who were
      very overweight and/or had comorbid conditions. Change in standardized BMI was
      assessed. Overall, participants demonstrated a significant reduction in
      standardized BMI, t (40)=6.6, p<.001. Further analyses indicated that
      participants who were severely obese and children with a comorbidity
      significantly reduced their zBMI (t (11)=4.0, p<.01; t (14)=3.9, p<.01,
      respectively). Children who were severely obese reduced their BMI percentile by
      .2 (SD=.2) and those with a comorbidity reduced their BMI percentile by .6
      (SD=.9). Nonsignificant interaction effects indicated comparable weight
      reductions in severely obese and overweight/obese participants, F (1,39) = 1.49,
      ns. Also, those with comorbidities and those without comorbidities experienced
      similar weight reductions, F (1,39)=.7, ns. This study provides promising
      evidence for the applicability of an evidence-based treatment for weight
      management in clinical practice.

PMID- 21873760
TI  - [What happens when the child gets bacteriophage per os?].
AB  - The aim of the work was to define the distribution of phages administered per os
      to children for medical reasons, and the immune response. 102 children aged from
      5 days to 15 years with different diseases of bacterial etiology (pneumonia,
      sepsis, urinary infection, pharyngitis/sinusitis, enteral infection) were
      monitored. Pyobacteriophage was being included into the complex therapy. The drug
      was administered per os. In 6/7 of blood, 48/55 urine and 64/75 stool samples
      taken on the 3-5th day of treatment different components of pyobacteriophage were
      revealed. The titers varied from 103 to 105 pfu/ml. No age differences were seen.
      In two weeks after the onset of the phagotherapy the antibodies to phages were
      tested in the blood serum using the neutralization reaction method. The blood
      samples were taken from 31 patients. In 14 of them the antibodies neutralizing
      52.5-97.3% of the phage activity were seen. A significant age-related peculiarity
      was determined: in newborns and infants the antibodies were not revealed or their
      activity was low. Obtained results confirm the reasonability to use of peroral
      phagotherapy in gastro-intestinal infections. At the same time it was ascertained
      that the phages taken per os can permeate into the internal environment of the
      organism and thus the peroral phagotherapy can be used to treat systemic
      infections and urinary tract infections as well. Absence or low production of the
      antiphage antibodies in newborns and infants suggests high efficacy of the
      phagotherapy in this age group.

PMID- 21873761
TI  - Synthesis and characterization of nanocrystalline calcium sulfate for use in
      osseous regeneration.
AB  - Nanoparticles of calcium sulfate (nCS) have potential advantages as a ceramic
      matrix, scaffold and/or vehicle for delivering growth factors for osseous
      regeneration in a variety of clinical situations. The objectives of this study
      were to synthesize and characterize nanoparticles of hemihydrate calcium sulfate
      (nCS) and to develop a nCS-based system for bone regeneration. A cryo-vacuum
      method was used to process dihydrate CS into dihydrate nCS, which was then
      subjected to oven drying to produce hemihydrate. The nCS was sterilized by glow
      discharge treatment for use as a synthetic graft material for the treatment of
      bone defects. Electron microscopy showed that the nCS powder consisted of
      aggregates of closely arranged acicular crystals, approximately 30-80 nm in
      width, 400-600 nm in length and approximately 80-100 nm in diameter, providing a
      surface area about ten times that of conventional CS. Thorough physico-chemical
      characterization confirmed the composition and phase of the material. Cell
      viability/metabolic activity assays and alkaline phosphate assays confirmed the
      safety and biocompatibility of nCS. Release kinetics for adsorbed platelet
      derived growth factor and bone morphogenetic protein-2 (BMP-2) suggests that nCS
      may serve as an appropriate vehicle for slow release delivery of these agents.
      The studies presented here give evidence of the advantages of nCS as a scaffold
      to support osteoblastic cell activity.

PMID- 21873762
TI  - Protein diffusion in photopolymerized poly(ethylene glycol) hydrogel networks.
AB  - In this study, protein diffusion through swollen hydrogel networks prepared from
      end-linked poly(ethylene glycol)-diacrylate (PEG-DA) was investigated. Hydrogels
      were prepared via photopolymerization from PEG-DA macromonomer solutions of two
      molecular weights, 4600 Da and 8000 Da, with three initial solid contents: 20, 33
      and 50 wt/wt% PEG. Diffusion coefficients for myoglobin traveling across the
      hydrogel membrane were determined for all PEG network compositions. The diffusion
      coefficient depended on PEG molecular weight and initial solid content, with the
      slowest diffusion occurring through lower molecular weight, high-solid-content
      networks (D(gel) = 0.16 +/- 0.02 * 10(-8) cm(2) s(-1)) and the fastest diffusion
      occurring through higher molecular weight, low-solid-content networks (D(gel) =
      11.05 +/- 0.43 * 10(-8) cm(2) s(-1)). Myoglobin diffusion coefficients increased
      linearly with the increase of water content within the hydrogels. The
      permeability of three larger model proteins (horseradish peroxidase, bovine serum
      albumin and immunoglobulin G) through PEG(8000) hydrogel membranes was also
      examined, with the observation that globular molecules as large as 10.7 nm in
      hydrodynamic diameter can diffuse through the PEG network. Protein diffusion
      coefficients within the PEG hydrogels ranged from one to two orders of magnitude
      lower than the diffusion coefficients in free water. Network defects were
      determined to be a significant contributing factor to the observed protein
      diffusion.

PMID- 21873763
TI  - A differential capacitive electrical field sensor array for contactless
      measurement of respiratory rate.
AB  - Although respiratory rate is an important vital sign for early detection of
      deterioration, on general wards it is not routinely monitored. Since patients may
      not tolerate cables attached to their chest, we developed an unobtrusive and
      contactless measurement method which can be placed under a mattress. The sensor
      array uses the Maxwell-Wagner relaxation effect by capacitive injection of a high
      frequency voltage into the torso and subsequent measurement of respiratory
      induced phase shift. Simulations of the entire measurement scenario indicate an
      improved signal-to-noise ratio if a differential method is applied with specific
      positioning of the electrodes. A prototype was designed and the simulations were
      confirmed with measurements on a phantom and in a human self-experiment by the
      authors using self-constructed hardware. Movement artifacts were detected using
      an artifact detection algorithm which allows reliable estimation of the
      respiratory rate.

PMID- 21873764
TI  - Efficiency optimization of wireless power transmission systems for active capsule
      endoscopes.
AB  - Multipurpose active capsule endoscopes have drawn considerable attention in
      recent years, but these devices continue to suffer from energy limitations. A
      wireless power supply system is regarded as a practical way to overcome the power
      shortage problem in such devices. This paper focuses on the efficiency
      optimization of a wireless energy supply system with size and safety constraints.
      A mathematical programming model in which these constraints are considered is
      proposed for transmission efficiency, optimal frequency and current, and overall
      system effectiveness. To verify the feasibility of the proposed method, we use a
      wireless active capsule endoscope as an illustrative example. The achieved
      efficiency can be regarded as an index for evaluating the system, and the
      proposed approach can be used to direct the design of transmitting and receiving
      coils.

PMID- 21873765
TI  - Investigating potential physicochemical errors in polymer gel dosimeters.
AB  - Measurement errors in polymer gel dosimetry can originate either during
      irradiation or scanning. One concern related to the exothermic nature of
      polymerization reaction was that the heat released in polymer gel dosimeters
      during irradiation modifies their dose response. In this paper, the effect of
      heat released from the exothermal polymerization reaction on the dose response of
      a number of dosimeters was studied. In addition, we investigated whether heat
      generated geometric distortion existed in newly proposed gel dosimeters that
      contain highly thermoresponsive polymers. Our results suggest that despite a
      significant internal temperature increase in some gel compositions, their dose
      responses are not affected when oxygen is well expelled mechanically from the gel
      mixture. We also report on significant pre-irradiation instability in some
      recently developed polymer gel dosimeters but that geometric distortions were not
      observed. Data obtained by a set of small calibration vials are compared to those
      obtained from larger phantoms, and potential physicochemical causes of deviations
      between them are identified.

PMID- 21873766
TI  - Phase-uncertainty quality map for two-point Dixon fat-water separation.
AB  - This work investigates and compares two different phase-correction algorithms for
      Dixon fat-water separation and two different quality maps (QM) for region
      growing: the original QM, based on phase gradients, and a QM based on phase
      uncertainty, proposed in this article. A spoiled dual-gradient-echo sequence was
      employed at 1.5 T to acquire in-phase and out-of-phase images of joints, parotid
      glands, abdomen and test objects. All 97 datasets were processed eight times
      each: with two different phase correction algorithms (original and hierarchical
      phase correction), with two different QM, and with/without removing linear
      component of the phase drifts associated with dual-echo acquisitions and bipolar
      readout gradient waveforms. The linear component of the phase drift along the
      readout direction was found to reach 4.1 degrees  pixel(-1), depending on the
      geometric parameters. Pre-processing to remove linear phase shifts has little
      impact on outcome. The hierarchic phase-correction algorithm outperformed the
      original phase-correction algorithm in all applications. The proposed phase
      uncertainty QM provides a small performance improvement in clinical images, but
      can be vulnerable to flow-related phase shifts in bright vessels. Overall the
      most successful phase-correction technique employed phase-uncertainty QMs and
      hierarchic algorithms, with pre-processing to correct the linear phase drift
      associated with dual-echo acquisitions and bipolar readout gradient waveform.

PMID- 21873767
TI  - Optically stimulated luminescence in vivo dosimetry for radiotherapy: physical
      characterization and clinical measurements in (60)Co beams.
AB  - A commercial optically stimulated luminescence (OSL) dosimetry system was
      investigated for in vivo dosimetry in radiation therapy. Dosimetric
      characteristics of InLight dot dosimeters and a microStar reader (Landauer Inc.)
      were tested in (60)Co beams. The reading uncertainty of a single dosimeter was
      0.6%. The reproducibility of a set of dosimeters after a single irradiation was
      1.6%, while in repeated irradiations of the same dosimeters it was found to be
      3.5%. When OSL dosimeters were optically bleached between exposures, the
      reproducibility of repeated measurements improved to 1.0%. Dosimeters were
      calibrated for the entrance dose measurements and a full set of correction
      factors was determined. A pilot patient study that followed phantom validation
      testing included more than 100 measured fields with a mean relative difference of
      the measured entrance dose from the expected dose of 0.8% and the standard
      deviation of 2.5%. In conclusion, these results demonstrate that OSL dot
      dosimeters represent a valid alternative to already established in vivo dosimetry
      systems.

PMID- 21873768
TI  - The effects of acoustic attenuation in optoacoustic signals.
AB  - In this paper, it is demonstrated that the effects of acoustic attenuation may
      play a significant role in establishing the quality of tomographic optoacoustic
      reconstructions. Accordingly, spatially dependent reduction of signal amplitude
      leads to quantification errors in the reconstructed distribution of the optical
      absorption coefficient while signal broadening causes loss of image resolution.
      Here we propose a correction algorithm for accounting for attenuation effects,
      which is applicable in both the time and frequency domains. It is further
      investigated which part of the optoacoustic signal spectrum is practically
      affected by those effects in realistic imaging scenarios. The validity and
      benefits of the suggested modelling and correction approaches are experimentally
      validated in phantom measurements.

PMID- 21873769
TI  - Efficient mining of association rules for the early diagnosis of Alzheimer's
      disease.
AB  - In this paper, a novel technique based on association rules (ARs) is presented in
      order to find relations among activated brain areas in single photon emission
      computed tomography (SPECT) imaging. In this sense, the aim of this work is to
      discover associations among attributes which characterize the perfusion patterns
      of normal subjects and to make use of them for the early diagnosis of Alzheimer's
      disease (AD). Firstly, voxel-as-feature-based activation estimation methods are
      used to find the tridimensional activated brain regions of interest (ROIs) for
      each patient. These ROIs serve as input to secondly mine ARs with a minimum
      support and confidence among activation blocks by using a set of controls. In
      this context, support and confidence measures are related to the proportion of
      functional areas which are singularly and mutually activated across the brain.
      Finally, we perform image classification by comparing the number of ARs verified
      by each subject under test to a given threshold that depends on the number of
      previously mined rules. Several classification experiments were carried out in
      order to evaluate the proposed methods using a SPECT database that consists of 41
      controls (NOR) and 56 AD patients labeled by trained physicians. The proposed
      methods were validated by means of the leave-one-out cross validation strategy,
      yielding up to 94.87% classification accuracy, thus outperforming recent
      developed methods for computer aided diagnosis of AD.

PMID- 21873770
TI  - Multi-view 3D echocardiography compounding based on feature consistency.
AB  - Echocardiography (echo) is a widely available method to obtain images of the
      heart; however, echo can suffer due to the presence of artefacts, high noise and
      a restricted field of view. One method to overcome these limitations is to use
      multiple images, using the 'best' parts from each image to produce a higher
      quality 'compounded' image. This paper describes our compounding algorithm which
      specifically aims to reduce the effect of echo artefacts as well as improving the
      signal-to-noise ratio, contrast and extending the field of view. Our method
      weights image information based on a local feature coherence/consistency between
      all the overlapping images. Validation has been carried out using phantom,
      volunteer and patient datasets consisting of up to ten multi-view 3D images.
      Multiple sets of phantom images were acquired, some directly from the phantom
      surface, and others by imaging through hard and soft tissue mimicking material to
      degrade the image quality. Our compounding method is compared to the original,
      uncompounded echocardiography images, and to two basic statistical compounding
      methods (mean and maximum). Results show that our method is able to take a set of
      ten images, degraded by soft and hard tissue artefacts, and produce a compounded
      image of equivalent quality to images acquired directly from the phantom. Our
      method on phantom, volunteer and patient data achieves almost the same signal-to
      noise improvement as the mean method, while simultaneously almost achieving the
      same contrast improvement as the maximum method. We show a statistically
      significant improvement in image quality by using an increased number of images
      (ten compared to five), and visual inspection studies by three clinicians showed
      very strong preference for our compounded volumes in terms of overall high image
      quality, large field of view, high endocardial border definition and low cavity
      noise.

PMID- 21873771
TI  - Computational identification and analysis of single-nucleotide polymorphisms and
      insertions/deletions in expressed sequence tag data of Eucalyptus.

PMID- 21873772
TI  - Molecular sexing and analysis of CHD1-Z and CHD1-W sequence variations in wild
      common quail (Coturnix c. coturnix) and domesticated Japanese quail (Coturnix c.
      japonica).

PMID- 21873773
TI  - Polymorphic microsatellite loci in Chinese piebald odorous frog (Odorrana
      schmackeri).

PMID- 21873774
TI  - Genetic variability in Sambucus nigra L. clones: a preliminary molecular
      approach.

PMID- 21873775
TI  - Consistent effects of single and combined SNP(s) within bovine paired box 7 gene
      (Pax7) on growth traits.

PMID- 21873776
TI  - Development of twenty-six microsatellite loci from Crassostrea hongkongensis and
      cross-species amplification in two closely related species.

PMID- 21873778
TI  - A preliminary linkage map using spotted melanic laboratory strains of the
      livebearing fish Phalloceros caudimaculatus var. reticulata (Cyprinodontiformes:
      Poeciliidae).

PMID- 21873779
TI  - Dopamine metabolism-related gene polymorphisms in Roma (Gypsy) and Hungarian
      populations.

PMID- 21873780
TI  - [Transcriptomic regulation and molecular mechanism of polygenic tumor at
      different stages].
AB  - The research team on the National Key Scientific Program of China:
      "Transcriptomic regulation and molecular mechanism research of polygenic tumor at
      different stages" has focused on the field of transcriptomics of 4 common
      polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer,
      colorectal cancer, and glioma. Extensive laboratory work has been carried out on
      the expression and regulation of tumor transcriptomics; identification of tumor
      suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs,
      and comparative study of specific gene/protein cluster of tumor transcriptomics
      and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q,
      SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional
      regulation genes during the stage of tumor initiation and invasion.
      Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target
      genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma
      signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network
      of colorectal cancer metastasis related gene NGX6 have been thoroughly
      elucidated. These fruitful Results imply that the changes of key molecules in
      crucial signal pathway will cause severe dysfunction in signal transduction and
      gene regulation network in polygenic tumors, indicating that in the category of
      pathogenesis,these tumors may further classify as the "Disease of gene signal
      transduction and gene regulation network disorder". The researches have laid
      solid foundation for revealing the molecular mechanism and transcriptomic
      regulation of polygenic tumors at different stages.

PMID- 21873781
TI  - [Progress of TSC-22 gene research].
AB  - Transformation growth factor beta -inducible gene 22 (TSC-22) is a putative
      negative growth regulation and tumor suppressor gene. It has the ability to
      combine with other transcription factors to regulate the cell growth and
      apoptosis. TSC-22 is lowly expressed in many types of tumors,which may be related
      to the tumorgenesis and development.

PMID- 21873782
TI  - Distribution and expression of alternative splice isoforms of NOR1 in human
      tissues and cell lines.
AB  - OBJECTIVE: To analyze the distribution and subcellular localization of NOR1
      alternative splice isoforms in human tissues and cell lines. METHODS: NOR1 open
      reading frame(ORF) was amplified from human fetal brain cDNA library and
      subcloned into pCMV/myc vector. The level of NOR1 mRNA in human tissues was
      determined by real-time RT-PCR. Region spanning exon 2 was amplified from cDNA or
      genomic DNA by specific primers and sequenced. The expression plasmids of NOR1
      were transfected into cells and immunofluoresence assay was performed to
      determine the subcellular localization of NOR1 protein isoforms in human cells.
      RESULTS: The expression of NOR1 mRNA was high in human adult testis, moderate in
      human fetus nasopharynx, trachea, brain, and kidney tissues, and weak or
      undetectable in other tissues. Two splice variants of human NOR1 gene resulted
      from alternative splicing at exon 2 were identified. Both of isoform 1 and
      isoform 2 mRNA were detected in human fetus brain. Isoform 2 was the sole isoform
      in other tissues but brain. Only isoform 2 mRNA was detected in cell lines used
      in this study, though no genomic deletion of exon 2 could be found in all these
      cell lines. Immunofluoresence assay showed both isoform 1 and isoform 2 proteins
      were distributed in cytoplasm. CONCLUSION: Alternative splice isoforms of tumor
      suppressor gene NOR1 are identified. NOR1 isoform 1 and isoform 2 are both
      detected in fetus brain. NOR1 isoform 2 lacking of exon 2 is the sole isoform in
      multiple tissues except for brain. The exon 2 encoded peptide does not affect the
      subcellular location of NOR1 protein.

PMID- 21873783
TI  - miR-149 promotes epithelial-mesenchymal transition and invasion in nasopharyngeal
      carcinoma cells.
AB  - OBJECTIVE: To investigate the function and mechanism of miR-149 in nasopharyngeal
      carcinoma (NPC). METHODS: The expression of miR-149 was examined by real-time PCR
      and calculated by 2(-??Ct) method. The cell proliferation was analyzed by MTT
      assay. The cell migration and invasion were shown by the wound healing assay and
      transwell migration assay, and the expression of E-cadherin was detected by
      Western blot. RESULTS: The expression of miR-149 was higher in NPC cell lines 5
      8F and 6-10B than that in normal immortalized nasopharyngeal epithelial NP69. MTT
      assay showed that miR-149 promoted the proliferation of NPC cell lines. The wound
      healing assay showed miR-149 promoted the mobility and invasion of NPC cell
      lines. Inhibition of miR-149 reduced the ability of NPC cell lines to proliferate
      and invade. miR-149 downregulated the expression of E-cadherin, whereas antagomir
      which mediated knockdown of miR-149 significantly upregulated the expression of E
      cadherin. CONCLUSION: miR-149 might be involved in the invasion and metastasis of
      NPC through regulation of epithelial-mesenchymal transition (EMT).

PMID- 21873777
TI  - Characterization of novel polymorphic microsatellite markers from the cDNA
      library of Japanese scallop Mizuhopecten yessoensis and cross-species
      amplification in bay scallop Argopecten irradians.

PMID- 21873784
TI  - [Optimization of prokaryotic expression condition and purification of anti-cancer
      protein NOR1 in E.coli].
AB  - OBJECTIVE: To optimize the induction condition of human NOR1 gene expression in
      E.coli. and purify NOR1 recombinant proteins. METHODS: A full-length cDNA of
      human NOR1 was inserted into the corresponding region of pET28b expression vector
      to yield recombinant prokaryotic expression vector pET28b-NOR1. The prokaryotic
      expression vector pET28b-NOR1 was introduced into the bacterial host E.coli
      Rosettablue(DE3). Recombinant NOR1 protein was induced at different conditions.
      Induction condition was optimized to obtain high yield of recombinant protein. At
      last, the recombinant NOR1 protein was purified by Ni-IDE chromatography resin.
      RESULTS: Recombinant NOR1 protein was induced by IPTG in a dose-dependent manner.
      Increase of kanamycin concentration and induction temperature resulted in high
      yield of recombinant protein. The most recombinant protein was found in inclusion
      bodies. The recombinant His-NOR1 protein was purified with Ni-IDE chromatography
      resin under denature condition. CONCLUSION: IPTG, kanamycin concentration and
      temperature can affect the expression of recombinant NOR1 protein in pET28b
      system. High yield of recombinant NOR1 protein is achieved by inducing 1 mmol/L
      IPTG and 200 MUg/mL kanamycin at 37 degree. Recombinant His-NOR1 protein with
      high purity is purified.

PMID- 21873785
TI  - Berberine inhibits the invasion and metastasis of nasopharyngeal carcinoma cells
      through Ezrin phosphorylation.
AB  - OBJECTIVE: To determine the molecular mechanism of berberine (BBR) inhibiting the
      metastasis and invasion of nasopharyngeal carcinoma 5-8F cells, and identify
      whether berberine suppresses the tumor-invasive action through inhibiting Ezrin
      or phosphate-Ezrin. METHODS: The non-cytotoxic concentration of berberine was
      detected by MTT assay. Filopodia formation of 5-8F cells was observed by electron
      microscope. The invasion and motility of 5-8F cells with berberine treatment were
      measured with Trans-well assay. Western blot was used to investigate the Ezrin
      and phos-Ezrin expression in 5-8F cells treated by berberine. pcDNA3.1-Ezrin and
      pcDNA3.1-Ezrin M were transfected into 6-10B cells. The inhibitory effect of
      berberine on the motility and invasion of 6-10B-pcDNA3.1-Ezrin and 6-10B-pcDNA3.1
      Ezrin M was detected, respectively. RESULTS: Berberine non-cytotoxic
      concentration was 0-40 MUmol/L. After being treated by berberine, filopodia of 5
      8F cells obviously reduced, and the permeating artificial basement membrane cells
      largely decreased in both time- and concentration-dependent manner. There was
      significant difference compared with the control group (P<0.05). Berberine
      suppressed the phos-Ezrin expression of 5-8F cells in both time- and
      concentration-dependent manner (P<0.05), but the effect of berberine was weaker
      on 6-10B-pcDNA3.1-Ezrin M than on 6-10B-pcDNA3.1-Ezrin. CONCLUSION: Berberine
      inhibits nasopharyngeal carcinoma cell invasion through inhibiting phos-Ezrin
      expression and filopodia formation.

PMID- 21873786
TI  - Maintenance of Epstein-Barr virus latent genome in epithelial tumor cells during
      the cellular clonal expansion.
AB  - OBJECTIVE: To determine the maintenance and loss of Epstein-Barr virus (EBV)
      genome during the clonal expansion of the EBV-infected epithelial cells. METHODS:
      The epithelial tumor cell line, 293-EBV, in which the EBV genome was observed
      with green fluorescent protein (GFP) readout. After a dozen of passages, it
      contained cells with strong or weak GFP expression, and some with complete loss
      of EBV genome. The cell growth was then continuously observed under a confocal
      microscope. The cell dividing and GFP expression were also observed during the
      clonal expansion by being made into very low density. RESULTS: The cells moved
      around due to adherence and mobility, while the GFP expression remained unchanged
      in the undivided cells. The cells could form compact or loosen clones. The EBV
      genome easily persisted in those clones when cells were growing compactly. As the
      cell number increased, the GFP expression became weak or even died away at the
      sites of low density in the loosen clones. CONCLUSION: EBV-positive epithelial
      cells are able to sustain the EBV genome during its clonal expansion. The cells
      maintain EBV genomes by passing them to the daughter cells after replication.
      When the cells unsuccessfully inherit the EBV genome, the daughter cells may lose
      them which is related to the low cell density as well as the epithelial
      environment.

PMID- 21873787
TI  - [Methylation status of RASSF1A and clinical efficacy of neoadjuvant therapy in
      patients with advanced epithelial ovarian cancer].
AB  - OBJECTIVE: To explore the relation between methylation status of RAS association
      domain family 1A (RASSF1A) in patients with advanced epithelial ovarian cancer
      and the clinical efficacy of cisplatin based neoadjuvant therapy. METHODS: Forty
      patients with advanced epithelial ovarian cancer were selected and the
      methylation status of RASSF1A was evaluated by methylation specific PCR (MSP).
      The clinical efficacy was compared between patients with different methylation
      statuses of RASSF1A. RESULTS: The response rate of 15 patients with methylation
      status in the promoter region was 26.6% and that of 25 patients without
      methylation status was 48.0%, with significant difference (P<0.05). CONCLUSION:
      The methylation status of RASSF1A can influence the clinical efficacy of
      neoadjuvant therapy in patients with advanced epithelial ovarian cancer.

PMID- 21873788
TI  - [Definition and function identification of nucleus export signal of BRD7].
AB  - OBJECTIVE: To localize and define the region of nucleus export signal (NES) on
      BRD7, and determine the role of this region in nucleus export of the external
      protein. METHODS: Based on an in vitro expressed model of green fluorescence
      protein (GFP), we performed DNA walking analysis to set BRD7 into several
      sections according to the structural characteristics of BRD7, investigated the
      effect of different sections of BRD7 on nucleus export of GFP, defined the region
      of nucleus export signal sequence of BRD7, and further ascertained the content of
      amino acids in BRD7 and potential localization of BRD7 NES by bioinformatics.
      RESULTS: B7C1 fragments ranged from aa219 to aa450 in BRD7 were found to target
      the external protein GFP into the cytoplasm detected by GFP direct fluorescence,
      which could be inhibited by NES inhibitor Leptomycin B (LMB). This region was
      rich in hydrophobic amino acid residues but no typical NES with characteristics
      of leucine-rich sequence by bioinformatics. CONCLUSION: The region from aa219 to
      aa450 is primarily defined as an atypical NES in BRD7.

PMID- 21873789
TI  - [Effect of Mcl-1 antisense oligonucleotide on Hela cell biology and sensitivity
      of chemotherapy].
AB  - OBJECTIVE: To explore the effect of myeloid leukemia-1 (Mcl-1) gene on the
      proliferation and apoptosis of Hela cells and the sensitivity of cervical cancer
      chemotherapy by antisense technology. METHODS: Mcl-1 antisense oligonucleotide(AS
      ODN)was transfected into Hela cells with lipofectamine 2000. The expression of
      Mcl-1 was analyzed by Western blot, the cell viability was detected by MTT assay,
      and apoptosis was evaluated by flow cytometry. RESULTS: Mcl-1 AS-ODN arrested the
      cell cycle at G1/S,greatly inhibited the cell growth and induced apoptosis. The
      sensitivity of Hela cells on chemotherapy was low. There was obvious increase in
      the apoptosis rate by chemotherapy drugs and growth inhibition rate after
      inhibiting the expression of Mc1-1. CONCLUSION: Mcl-1 AS-ODN can not only inhibit
      Hela cell proliferation and induce apoptosis, but also increase the sensitivity
      of chemotherapy. Mcl-1 may be a potential target gene for cervical cancer
      chemotherapy.

PMID- 21873790
TI  - [Inflammatory factors promote the development of colorectal cancer].
AB  - OBJECTIVE: To study the change of inflammatory factors at different stages of
      colorectal cancer (CRC). METHODS: Thirty normal subjects, 30 patients with
      colorectal adenomatous polyps and 120 CRC patients at different stages were
      enrolled. IgG, IgM, and IgA levels, the inflammatory cytokines IL-2, 4, 6, 10,
      and 12 and the expression of TGF-beta 1 and VEGF in the serum were analyzed by
      ELISA or immunoturbidimetry. RESULTS: The serum concentrations of IL-12, TGF-beta
      1, and IL-6 in the CRC patients were statistically different compared with the
      normal and adenomatous polyps, and increased as the disease progressed (P<0.05).
      IL-6 reached the highest level in C phase of CRC.The serum concentrations of IL
      2, IL-4, and IL-10 were significantly different among the groups. VEGF serum
      levels in CRC Phase A and Phase B compared with other groups were statistically
      different, but other serum concentrations had no significant difference (P>0.05).
      The serum level of IgG, IgM, and IgA in the 3 groups showed no significant
      difference (P>0.05). CONCLUSION: The serum level of inflammatory cytokines TGF
      beta 1, IL-6, and IL-12 increases gradually with the development of CRC, which
      may change the microcirculation of patients with CRC, and promote the development
      of CRC.

PMID- 21873791
TI  - [RUNX3 promoter hypermethylation and prognosis of early surgically resected non
      small cell lung cancers].
AB  - OBJECTIVE: To determine the relation between the promoter methylation status of
      RUNX3 gene and clinicopathological parameters, prognosis of non-small cell lung
      cancer (NSCLC). METHODS: We collected 80 formalin-fixed paraffin-embedded lung
      cancer tissue samples from NSCLC patients who received postoperative adjuvant
      chemotherapy with cisplatin. Genomic DNA was extracted through phenol/chloroform
      extraction. The methylation status of RUNX3 was determined by nested methylation
      specific PCR (nMSP). We investigated the pathological and prognostic
      characteristics of NSCLC stratified by methylation status. RESULTS: The RUNX3
      promoter methylation was observed in 20 of the 80 NSCLC samples (25.0%).
      Methylation of RUNX3 was more frequent in adenocarcinomas (36%) than in squamous
      cell carcinomas (11%) (P=0.020). In multivariate Logistic regression, positive
      RUNX3 methylation status (P=0.011) was found to be independent disease-free
      survival factor as was N stage (P<0.001). Kaplan-Meier curves showed patients
      with RUNX3 methylation had a significantly poorer overall survival than those
      without methylation (P=0.003; log-rank test). In multivariate Cox proportional
      hazards regression analysis, RUNX3 methylation (RR:2.345, 95% CI:1.30-4.865,
      P=0.022) was a significant independent prognostic factor for the overall
      survival. CONCLUSION: RUNX3 methylation is a significant independent prognostic
      factor for disease-free survival and overall survival.

PMID- 21873792
TI  - [Recombinant expression of hepatoma associated gene and its protein function].
AB  - OBJECTIVE: To recombinant express hepatoma associated gene(HTA) and pre-test the
      function of HTA to determine the role of HTA in the development of liver cancer.
      METHODS: HTA338-616 was amplified from HepG2 cells and cloned into the
      prokaryotic expression vector pET21a(+)-MBP. The proteins MBP and MBP-HTA were
      induced, purified by His-tag magnetic bead purification kit and identified by
      Western blot and ELISA. HepG2 cells were stimulated with MBP or MBP-HTA proteins.
      MTT assay and colony formation assay were employed to examine the proliferation
      of these cells and the changes of cell cycle distribution were determined by flow
      cytometry. RESULTS: The prokaryotic expression plasmid pET21a(+)-MBP-HTA was
      successfully constructed. We got a 52 kD purified purpose protein.The
      proliferation of HepG2 cells stimulated with MBP-HTA was significantly higher
      than those stimulated with MBP and negative controls. HepG2 cells stimulated with
      MBP-HTA showed significant decrease fraction in G1 phase and increase fraction in
      S phase, and the cell proliferation was enhanced. CONCLUSION: HTA protein can
      significantly promote the proliferation of HepG2 cells, which may be related to
      the promotion of G1 phase to S phase.

PMID- 21873793
TI  - Expression of bone morphogenetic proteins and their receptors in the normal adult
      rat spinal cord.
AB  - OBJECTIVE: To observe the expression distribution of bone morphogenetic proteins
      (BMP) in the spinal cord of normal adult rats. METHODS: Expression of BMP2, BMP4,
      and BMP7, and their receptors BMPR Ia, BMPR Ib, and BMP II were detected by
      immunochemistry analysis in the spinal cord of normal adult rats. RESULTS:
      Expression of BMPR Ia or BMPR Ib was observed in the motor neurons of the
      anterior horn, sensory neurons of the dorsal horn, oligodentrocytes, some
      microglia, and some astrocytes. Expression of receptor BMPR II was found in the
      oligodentrocytes and motor neurons in the gray matter of anterior horn. It was
      also expressed in some glial fibrillary acidic protein (GFAP)-positive astrocytes
      in the white matter but not in the gray matter. BMP2 and BMP4 were not expressed
      in the spinal cord of normal adult rats by immunohistochemistry. BMP7 was
      expressed in all the APC-positive oligodentrocytes, all the NeuN-positive motor
      neurons in the anterior horn, and some astrocytes in the normal spinal cord.
      Phosphated pSmad 1/5/8 protein was expressed in all the oligodentrocytes, all the
      neurons, and some astrocytes, especially in the GFAP-positive astrocytes which
      were RC2-positive radial glia in the subventricular zone. CONCLUSION: BMP7, BMP
      receptors, and phosphated pSmad 1/5/8 are expressed in many types of cells
      whereas BMP2 and BMP4 are not expressed in the spinal cord of normal adult rats,
      which suggests an important function of BMP signal pathway in the neuron and glia
      of spinal cord.

PMID- 21873794
TI  - Incidence and risk factors of intraoperative awareness during general anesthesia.
AB  - OBJECTIVE: To investigate the incidence of awareness during general anesthesia
      and analyze the risk factors in anesthetic practice and patient populations.
      METHODS: A total of 2 300 patients who underwent general anesthesia were
      included. Perioperative data and anesthetic drugs were collected prospectively.
      Patients were interviewed twice postoperatively with the same structured
      questionnaire. Each patient was classified into categories as no awareness,
      possible awareness, and awareness. RESULTS: Twenty-one patients (0.91%)
      definitely reported awareness, and another 205 (8.91%) reported possible
      awareness. Few of the patients with awareness required psychological
      intervention. ASA physical status III-IV and propofol maintenance were associated
      risk factors of awareness. CONCLUSION: The incidence of intraoperative awareness
      is high in the clinical practice in major medical centers.

PMID- 21873795
TI  - [Effect of interleukin-17 and T helper cell 17 on acute heart allograft rejection
      in mice].
AB  - OBJECTIVE: To investigate the role of T helper cell 17(Th17) cells and their
      cytokines IL-17 in heart allograft rejection in mice. METHODS: The heart
      transplantation models were randomly divided into 2 groups: a allograft group
      (n=12) and an isograft group (n=12).On the post-operative day (POD) 3 and 7,
      serum IL-17 level was tested by enzyme-linked immunosorbent assay, and Th17 cells
      in heart grafts were measured by flow cytometry. The heart grafts were harvested
      and saved in 10% formalin, and then embedded in paraffin. RESULTS: Compared with
      the iso-graft group, the allograft group had a higher serum level of IL-17 on
      POD3 and POD7 (P<0.05), and the level of IL-17 was higher on POD7 than that on
      POD3 (P<0.05). The allograft group had more Th17 cells infiltrating in grafts on
      POD3 and POD7 (P<0.05) and there were more Th17 cells infiltrating on POD7 than
      that on POD3 (P<0.05). Histological examination showed that the prolongation of
      post transplantation time resulted in more rejection pathological changes.
      CONCLUSION: Th17 cells may play an important role in the development of heart
      transplant rejection. IL-17 may serve as a predictive parameter for allograft
      rejection in the future.

PMID- 21873796
TI  - [Effect of exercise on the quality of life and pulmonary function in patients
      with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the effect of exercise therapy on activity of daily
      living (ADL) and lung function in patients with chronic obstructive pulmonary
      disease (COPD). METHODS: A total of 122 patients with moderate to severe COPD
      received routine treatment.The patients were divided into 2 groups randomly.
      Sixty-two patients in the experimental group received respiratory training on the
      basis of respiratory pathophysiology and aerobic exercise for 1 year. Medical
      research council scale (MRC) score, ADL score, 6-min walking distance, and lung
      function were measured. RESULTS: The MRC grade after the exercise therapy was
      lower than that before the exercise therapy in the experimental group (P<0.01)
      and the control group (P<0.05). The ADL score and 6-min walking distance
      increased compared with that before the respiratory training (P<0.05).After the
      respiratory training, the ADL score and 6-min walking distance had significant
      difference between the experimental group and the control group (P<0.05).
      CONCLUSION: Long term and individual exercise therapy can relieve dyspnea, and
      improve the exercise tolerance and quality of life in COPD patients.

PMID- 21873797
TI  - [Sperm acrosome reaction detection in intrauterine insemination].
AB  - OBJECTIVE: To investigate the relationship between sperm acrosome reaction (AR)
      and the clinical pregnancy rate of intrauterine insemination (IUI). METHODS: We
      detected the sperm spontaneous AR rate and Ca2+ ionophore A23187-induced AR rate
      in 128 patients who accepted IUI treatment, collected their clinical data and
      analysed the relationship between sperm AR rate and clinical pregnancy rate of
      IUI. RESULTS: There was no statistical difference between the spontaneous AR
      rates in the pregnant group and the non-pregnant group (7.7% vs. 7.0%, P>0.05),
      but there was statistical difference between the induced AR rates(51.9 % vs.
      43.5%, P<0.05). There was statistical difference in the clinical pregnancy rate
      among the 3 IUI groups divided by induced AR rate (<=20.0%, 20.1%-49.9%, and
      >=50.0%; 4.8% vs. 12.5% vs. 18.6%, P<0.05). CONCLUSION: The spontaneous AR rate
      has nothing to do with the clinical pregnancy rate of IUI, but the induced AR
      rate is associated with the clinical pregnancy rate of IUI.

PMID- 21873798
TI  - [Development of health service in Hunan Province].
AB  - OBJECTIVE: To study the health service development in Hunan Province, and to find
      out the advantages and disadvantages, and to make tentative specific suggestions.
      METHODS: Comparison was made in Yunnan, Hunan, and Zhejiang Provinces in 4 major
      areas: health institutions, personnels, facilities, and funding. RESULTS: The
      overall health service of Hunan Province was good: The health resources
      increased, the allocations were reasonable, and the health expenditure decreased.
      Some problems appeared, such as backward primary health, shortage of medical
      talents, inefficient use of hospital beds, deducted government investment,
      increased business income, and large urban-rural gap. CONCLUSION: There is urgent
      need to further develop health institutions and increase personnels, particularly
      improving the primary health care and making use of traditional Chinese medicine;
      improving the management of hospital beds to increase efficiency, increasing
      financial support to reduce the patients' burden, and ensuring the need of rural
      health care.

PMID- 21873799
TI  - A case of severe acute pancreatitis and cholangitis presenting as initial
      complaints of hepatocellular carcinoma.
AB  - Jaundice occurs in 19%-40% of the hepatocellular carcinoma (HCC) patients. HCC
      associated jaundice may be divided into hepatocellular and icteric types in terms
      of its underlying pathophysiology. The jaundice of icteric type is caused by
      obstruction of the bile duct through cancer embolus, blood clot, biliary sludge,
      tumor compression or infiltration. Jaundice and epigastric discomforts are the
      main clinical manifestations. In the present case, severe acute pancreatitis and
      acute cholangitis presenting as initial complaints of icteric type HCC were quite
      rare. A tumor located at the central lobe of the liver and a cancer embolus at
      the lower part of the common bile duct (CBD) were detected by CT scan. Curative
      resection of HCC with CBD exploration eradicated both the tumor and the embolus,
      and no recurrence was found after a 36 month follow-up.

PMID- 21873800
TI  - Type 2 diabetes in well-controlled hypertension.

PMID- 21873801
TI  - Incremental diagnostic value of regional myocardial blood flow quantification
      over relative perfusion imaging with generator-produced rubidium-82 PET.
AB  - BACKGROUND: Myocardial blood flow (MBF) can be measured with positron emission
      tomography (PET) and its quantification should provide diagnostic information
      beyond that obtained through standard visual analysis. However, this possibility
      has not been fully studied with PET and generator-produced rubidium-82 (82Rb). We
      evaluated regional MBF in segments with and without ischemia using 82Rb PET in
      patients with coronary artery disease (CAD). METHODS AND RESULTS: Rest and stress
      82Rb PET and coronary angiography were performed for 12 patients with CAD. Based
      on angiography and relative 82Rb perfusion images, segments were classified into
      4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no
      ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia
      without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed
      reduced hyperemic MBF compared with Group C (P < 0.05 vs. Group C) [Group A
      (n=16) 1.28 +/- 0.58 ml.min-1.g-1; Group B (n=11) 1.72 +/- 0.64 ml.min-1.g-1;
      Group C (n=9) 2.60 +/- 1.09 ml.min-1.g-1; Group D (n=2) 2.33 ml.min-1.g-1].
      Coronary flow reserves were inversely correlated with percent diameter stenosis
      (r=0.76, P < 0.0001). CONCLUSIONS: Segments with ischemia and coronary stenosis
      had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also
      had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification
      using 82Rb PET may provide additional diagnostic information.

PMID- 21873802
TI  - Intensive immunosuppressive therapy improves pulmonary hemodynamics and long-term
      prognosis in patients with pulmonary arterial hypertension associated with
      connective tissue disease.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) remains a serious disease
      characterized by elevated pulmonary artery pressure (PAP) and increased pulmonary
      vascular resistance (PVR). Among its subtypes, PAH associated with connective
      tissue disease (CPAH) has the worse prognosis, because of resistance to
      conventional vasodilator therapy. We hypothesized that intensive
      immunosuppressive therapy (IIT) could improve the pulmonary hemodynamics in CPAH.
      METHODS AND RESULTS: In our pulmonary hypertension (PH) cohort of 182 patients,
      we evaluated 13 consecutive patients with CPAH who received IIT combined with
      cyclophosphamide and glucocorticosteroids (IIT group, mean age 45 +/- 8 years, 12
      females and 1 male). We compared them with 8 historical controls (control group:
      mean age 52 +/- 18 years, 8 females) for pulmonary hemodynamics and prognosis.
      Both groups were treated with conventional vasodilator therapy. Although the mean
      PAP (mPAP) remained unchanged in the control group, IIT significantly decreased
      mPAP (40 +/- 9 to 29 +/- 11 mmHg, P < 0.01) and tended to decrease PVR (700 +/-
      434 to 481 +/- 418 dyne.s.cm-5, P=0.07). Importantly, in 6 of the 13 patients in
      the IIT group, mPAP was almost normalized (< 25 mmHg) and remained stabilized for
      more than 1 year. Furthermore, the IIT group showed significantly better
      prognosis compared with the control group (P<0.01). CONCLUSIONS: These results
      suggest that IIT as well as conventional vasodilator therapy improves the
      pulmonary hemodynamics and long-term prognosis of patients with CPAH.

PMID- 21873803
TI  - Low concordance between positive antibodies to thyroperoxidase and thyroid
      ultrasound autoimmune pattern in pregnant women.
AB  - The diagnostic and prognostic role of thyroid ultrasound (TUS) in pregnant women
      positive for antibodies to thyroperoxidase (TPOAb) is unclear.  The aim of our
      study was to compare the relation of ultrasound thyroid texture to the thyroid
      laboratory tests in pregnant women and controls.  Using a semi-quantitative
      assessment we compared TUS in two groups of women with positive TPOAb and/or with
      thyroid dysfunction (TSH out of 0.06-3.67 mIU/L): 186 women in 1(st) trimester of
      pregnancy recruited from universal screening and 67 asymptomatic age-comparable
      non-pregnant non-postpartum women recruited from screening of general population
      (controls).  Women with previous history of thyroid diseases were excluded.  Only
      64/131 (48.9 %) of TPOAb-positive pregnant women were TUS-positive (TUS with
      autoimmune pattern) in comparison with 35/49 (71.4 %) TPOAb-positive controls (p
      <0.011).  Pregnant women had more often TSH >10.0 mIU/L if they were TPOAb
      positive/TUS-positive as compared to those TPOAb-positive/TUS-negative (8/64
      (12.5 %) vs. 0/67 (0 %), p = 0.009).  The prevalence of preterm deliveries among
      TPOAb-positive women was significantly lower if TPOAb-positivity was not
      accompanied by TUS-positivity (2/67 (3.0 %) vs. 10/64 (15.6 %) in TPOAb
      positive/TUS-positive women, p = 0.028).  In conclusion, nearly half of the TPOAb
      positive pregnant women did not have an autoimmune pattern in TUS.  Normal TUS
      image in TPOAb-positive pregnant women might be a protective factor for preterm
      delivery.

PMID- 21873804
TI  - The antioxidant N-acetylcysteine promotes atherosclerotic plaque stabilization
      through suppression of RAGE, MMPs and NF-kappaB in ApoE-deficient mice.
AB  - AIMS: N-acetylcysteine (NAC) has antioxidant and anti-inflammatory properties. To
      explore the mechanisms underlying atherosclerotic plaque stabilization induced by
      NAC, we examined the effects of NAC administration in apoE-deficient mice on the
      expression of the receptor of advanced glycation end products (RAGE), matrix
      metalloproteinases (MMPs) and the activation of nuclear factor kappa B (NF
      kappaB) in atherosclerotic plaques. METHODS: 10-week-old ApoE(-/-) mice fed with
      atherogenic diet were treated with NAC (200 mg/kg/ day) for 8 weeks. Serum lipid,
      glucose and malondialdehyde (MDA) were detected. The size and composition of
      atherosclerotic plaques were measured by en face analysis, Movat staining,
      immunofluorescence and immunohistochemistry, respectively. Reactive oxygen
      species (ROS) generation in aortic root was tested by DHE staining. The levels of
      vascular cell adhesion molecule-1(VCAM-1), NF-kappaB, phosphor-NF-kappaB, I
      kappaB, phosphor-I-kappaB, RAGE, MMP2 and MMP9 in descending arteries were
      analyzed by Western blot. RESULTS: ApoE(-/-) mice administrated with NAC
      displayed reduced serum MDA level and impaired ROS generation in aortic root.
      However, NAC did not affect the levels of plasma glucose, lipids and the size of
      atherosclerotic lesions. Analysis of plaque composition showed decreased amounts
      of macrophages, lipid deposition, but not smooth muscle cells, and increased
      collagen content in atherosclerotic lesions in apoE(-/-) mice administered with
      NAC. Moreover, we found that NAC down-regulated the expression of VCAM-1, MMP2
      and MMP9, accompanied by inhibition of NF-kappaB activation and reduced
      expression of RAGE. CONCLUSION: In the present study, we show novel data to
      suggest that NAC promotes atherosclerotic plaque stabilization through
      suppression of RAGE, MMPs and NF-kappaB in apoE(-/-) mice.

PMID- 21873805
TI  - Association of circulating fractalkine (CX3CL1) and CX3CR1(+)CD4(+) T cells with
      common carotid artery intima-media thickness in patients with chronic kidney
      disease.
AB  - AIM: Fractalkine (CX3CL1), a chemokine, and its receptor CX3CR1 (expressed on T
      lymphocytes), have been shown to be abnormal in atherosclerosis. We investigated
      whether CX3CL1 levels and CX3CR1 expression were altered in patients with chronic
      kidney disease (CKD) and their association with common carotid artery intima
      media thickness (CCA-IMT). METHODS: CX3CR1 expression on CD4(+) T cells was
      analyzed by flow cytometry in 62 healthy controls (HC) and 128 Stage III-V CKD
      subjects. Fractalkine and highly sensitive C-reactive protein (hsCRP) were
      analyzed by ELISA. CCA-IMT was measured by ultrasound. RESULTS: Compared to HC,
      CKD patients exhibited a 2.5-fold increase in the CD4(+)CX3CR1(+) T cell
      population (14.8+/-0.6 vs 5.9+/-0.34%, p < 0.0001). The expression of CX3CR1 was
      largely restricted to those CD4(+) cells that lacked CD28 co-stimulatory
      molecule. Fractalkine (pg/mL) and hsCRP (ug/mL) levels were increased in CKD
      subjects (510.6+/-61.6 vs. 239.7+/-9.67, p =0.003, and 93.8+/- 5.3 vs. 48.4+/
      6.8, p < 0.0001), as was the CCA-IMT (0.71+/-0.01 vs. 0.56+/-0.01 mm, p <
      0.0001). There was a significant relationship between CD4(+)CX3CR1(+) T cells and
      fractalkine levels (r = 0.2, p =0.01). CCA-IMT correlated positively with
      CX3CR1(+) T cells (r =0.34, p < 0.0001), CD4(+) CX3CR1(+) T cells (r =0.39, p <
      0.0001), CD4(+)CD28(null)CX3CR1(+) T cells (r =0.23, p =0.02), fractalkine (r
      =0.3, p =0.001), age (r =0.33, p < 0.0001) and diabetes (p =0.01). On multiple
      regression, only CD4(+)CX3CR1(+) T cells and the presence of diabetes continued
      to show an association with IMT (p < 0.0001 and 0.0029 respectively).
      CONCLUSIONS: CKD subjects showed an increase in CD4(+)CX3CR1(+) T cell
      population, plasma fractalkine and IMT; the association of CD4(+)CX3CR1(+) T
      cells and plasma fractalkine with CCA-IMT indicates that the fractalkine-CX3CR1
      pathway may be important in the development and/or progression of atherosclerosis
      in CKD.

PMID- 21873806
TI  - Endocrine mechanisms responsible for different follicular development during the
      estrous cycle in Hatano high- and low-avoidance rats.
AB  - Hatano high- and low-avoidance rats (HAA and LAA strains, respectively) were
      selected and bred according to the avoidance rate in a shuttle-box task. Although
      they have clear strain differences in ovarian function, their endocrine
      mechanisms still remain to be clarified. Differences in female reproductive
      endocrinology between the strains were investigated by means of measuring the
      plasma concentration of reproductive hormones during the estrous cycle. LAA rats
      showed approximately threefold lower basal and surge levels of LH, a more than
      fourfold lower level of FSH surges and higher levels of inhibin A and inhibin B
      during the estrous cycle compared with the levels seen in HAA rats. The
      concentration of estradiol-17beta in the proestrous stage was significantly lower
      in LAA rats than in HAA rats. Additionally, LH and FSH secretions from primary
      cultured anterior pituitary cells with or without in vitro GnRH stimulation were
      lower in the cells derived from LAA rats and, in terms of FSH secretion, were
      unresponsive to GnRH in contrast to cells derived from HAA rats. Although an
      increased number of preantral follicles in diestrus were observed in LAA rats,
      number of hCG-induced ovulation was lower in LAA rats. LAA rats may have much
      more follicle growth during the early stage of folliculogenesis, but most
      follicles might not grow into mature follicles. These results strongly suggest
      that the strain difference in ovarian function of these two Hatano rats is due to
      the difference in the regulation of hypothalamo-hypophyseal system for
      gonadotropins secretion.

PMID- 21873807
TI  - Clathrin-mediated endocytosis of mammalian erythroid AE1 anion exchanger
      facilitated by a YXXPhi or a noncanonical YXXXPhi motif in the N-terminal
      stretch.
AB  - To explore the roles of the conserved YXXPhi-type motif in the erythroid-specific
      N-terminal stretch of anion exchanger 1 (AE1), cell surface expression and
      internalization of various mutants derived from murine erythroid AE1 tagged with
      an N-terminal enhanced green fluorescent protein and an extracellular FLAG (EGFP
      mAE1Flag) were explored in K562 and HEK293 cells. EGFP-mAE1Flag showed rapid
      internalization, in association with the internalizations of transferrin and the
      endogenous AE1 chaperone-like protein glycophorin A in K562 cells. Disruption of
      the conserved Y72VEL sequence markedly reduced the internalization and increased
      the relative abundance of cell-surface AE1, whereas substitution of the N
      terminal region from bovine AE1 that lacks the relevant motif for the
      corresponding region had less of an effect on internalization. Deletion or
      substitution mutations of the Y7EDQL sequence in the bovine N-terminal stretch
      resulted in the decreased internalization of the AE1 proteins. Cell surface
      biotinylation and deglycosylation studies showed that approximately 30% of the
      cell-surface EGFP-mAE1Flag and several other mutants was sorted to the plasma
      membrane without N-glycan maturation in the Golgi apparatus. These findings
      indicate that the conserved YXXPhi sequence or a noncanonical YXXXPhi sequence in
      the N-terminal region facilitates the endocytic recycling of erythroid AE1
      through a clathrin-mediated pathway.

PMID- 21873808
TI  - Anaplastic atypical myeloma with extensive cutaneous involvement in a dog.
AB  - A 7-year-old, male, mixed breed dog was referred to the Veterinary Teaching
      Hospital at Kitasato University because of anorexia, lameness and multiple
      cutaneous lesions. Observation of bone marrow plasmacytosis, osteolytic bone
      lesions, serum myeloma protein and cutaneous infiltration of myeloma cells led us
      to a diagnosis of multiple myeloma (MM) with cutaneous involvement. Polymerase
      chain reaction and sequence analysis for the rearranged genes of immunoglobulin
      and T-cell receptor demonstrated that the neoplastic cells found in skin lesions
      or bone marrow are of B-lymphocyte lineage and share a common original precursor
      cell. The dog was treated with UW-Madison protocol or melphalan/prednisone
      protocol and survived 175 days. This is rare case of anaplastic MM with cutaneous
      involvement in dog.

PMID- 21873809
TI  - Seroprevalence of Torque teno sus virus types 1 and 2 in postweaning
      multisystemic wasting syndrome-suspected pigs and porcine circovirus type 2
      vaccinated normal pigs in southern Japan.
AB  - We investigated the seroprevalence rate of Torque teno sus virus types 1 (TTSuV1)
      and 2 (TTSuV2) in the sera of 38 post weaning multisystemic wasting syndrome
      (PMWS)-suspected pigs and 43 porcine circovirus type 2 (PCV2)-vaccinated normal
      pigs on 3 commercial pig farms in southern Japan by using nested polymerase chain
      reaction. High seroprevalence rate of TTSuVs was observed in both PMWS-suspected
      pigs (100%) and PCV2-vaccinated normal pigs (90.7%). The seroprevalence rate of
      TTSuV2 was significantly higher in the PMWS-suspected pigs than in PCV2
      vaccinated normal pigs (97.4% versus 81.4%, P<0.05), whereas no such difference
      was observed for TTSuV1 between the 2 groups of pigs. In both pig groups, the
      seroprevalence rate of TTSuV2 was significantly higher than that of TTSuV1
      (P<0.01-0.05). These results show that TTSuVs are highly seroprevalent in both
      PMWS-suspected pigs and PCV2-vaccinated normal pigs with TTSuV2 being more
      seroprevalent in the former than in the latter.

PMID- 21873810
TI  - Adenosine and ATP affect LPS-induced cytokine production in canine macrophage
      cell line DH82 cells.
AB  - Macrophages are essential for controlling the majority of infections, and are
      mediators of natural immunity. During infection, lipopolysaccharide (LPS)
      stimulates macrophages to produce pro-inflammatory cytokines. Adenosine and ATP
      released into the extracellular space by immunological stimuli have been shown to
      regulate various immune functions. More recently, it has been shown adenosine and
      ATP have a critical role on the physiological negative feedback mechanism for
      limitation and termination of tissue-specific and systemic inflammatory
      responses. It was useful and meaningful to gain information about interaction
      between LPS, which generates the inflammation, and adenosine and ATP, which
      terminate the inflammation. We evaluate effects of adenosine and ATP on the
      production of cytokines related to inflammation in canine macrophage cell line
      DH82 cells. Adenosine and ATP respectively increased the production of IL-10
      without affecting the production of IL-6, TNF-alpha and IL-12 in DH82 cells. In
      addition, adenosine and ATP prevented the production of LPS-induced IL-6, TNF
      alpha and IL-12 in DH82 cells. In contrast, adenosine and ATP potentiated LPS
      induced IL-10 production in DH82 cells. Moreover, adenosine, but not ATP
      inhibited LPS-induced expression of TLR4 in DH82 cells. These results suggest
      that conditions related to increased adenosine and/or ATP may play an important
      role in the inflammatory reactions.

PMID- 21873811
TI  - [Trend of complaints about foreign matter contamination and proposals for
      preventive measures].

PMID- 21873812
TI  - Method for determination of aflatoxin M1 in cheese and butter by HPLC using an
      immunoaffinity column.
AB  - A rapid, sensitive convenient method for determination of aflatoxin M1 (AFM1) in
      cheese and butter by HPLC was developed and validated. The method employs a safe
      extraction solution (mixture of acetonitrile, methanol and water) and an
      immunoaffinity column (IAC) for clean-up. Compared with the widely used method
      employing chloroform and a Florisil column, the IAC method has a short analytical
      time and there are no interference peaks. The limits of quantification (LOQ) of
      the IAC method were 0.12 and 0.14 ug/kg, while those of the Florisil column
      method were 0.47 and 0.23 ug/kg in cheese and buffer, respectively. The recovery
      and relative standard deviation (RSD) for cheese (spiked at 0.5 ug/kg) in the IAC
      method were 92% and 7%, respectively, while for the Florisil column method the
      corresponding values were 76% and 10%. The recovery and RSD for butter (spiked at
      0.5 ug/kg) in the IAC method were 97% and 9%, and those in the Florisil method
      were 74% and 9%, respectively. In the IAC method, the values of in-house
      precision (n=2, day=5) of cheese and butter (spiked at 0.5 ug/kg) were 9% and
      13%, respectively. The IAC method is superior to the Florisil column method in
      terms of safety, ease of handling, sensitivity and reliability. A survey of AFM1
      contamination in imported cheese and butter in Japan was conducted by the IAC
      method. AFM1 was not detected in 60 samples of cheese and 30 samples of butter.

PMID- 21873813
TI  - [Study on rapid analysis method of pesticide contamination in processed foods by
      GC-MS and GC-FPD].
AB  - A simple and rapid method using GC-MS and GC-FPD for the determination of
      pesticide contamination in processed food has been developed. Pesticides were
      extracted from a sample with ethyl acetate in the presence of anhydrous sodium
      sulfate, then cleaned up with a combination of mini-columns, such as macroporous
      diatomaceous earth, C18, GCB (graphite carbon black) and PSA. Recovery tests of
      57 pesticides (known to be toxic or harmful) from ten kinds of processed foods
      (butter, cheese, corned beef, dried shrimp, frozen Chinese dumplings, grilled
      eels, instant noodles, kimchi, retort-packed curry and wine) were performed, and
      the recovery rates were mostly between 70% and 120%. This method can be used to
      judge whether or not processed foods are contaminated with pesticides at
      potentially harmful levels.

PMID- 21873814
TI  - [Determination of pindone in agricultural products by LC-MS/MS].
AB  - A sensitive and selective analytical method for the determination of pindone in
      agricultural products by LC-MS/MS was developed. Pindone was extracted with
      acetone, and an aliquot of the crude extract was re-extracted with hexane. For
      lipid-rich samples, the crude extract was further cleaned up by acetonitrile
      hexane partitioning. The extract was cleaned up on a tandem graphitized carbon
      silica gel column. For brown rice, soybean, and tea, PSA column cleanup was added
      prior to LC-MS/MS determination. Average recoveries of pindone from brown rice,
      soybean, potato, spinach, cabbage, apple, orange, tomato, cucumber, and tea
      fortified at 0.001 mg/kg were 81-93%, and the relative standard deviations were 2
      7%. The limit of quantitation (S/N >= 10) of the developed method was 0.001 mg/kg
      for all the tested agricultural products.

PMID- 21873815
TI  - [Determination of 4-hydroxycoumarin rodenticides in animal products, fishery
      products, and honey by liquid chromatography-tandem mass spectrometry].
AB  - A sensitive and selective method for the determination of 4-hydroxycoumarin-type
      rodenticides (warfarin, coumatetralyl, bromadiolone, and brodifacoum) in animal
      products, fishery products, and honey was developed. 4-Hydroxycoumarin
      rodenticides were extracted with acidified acetone, and the crude extract was
      purified by liquid-liquid partitioning followed by PSA column cleanup. Gradient
      liquid chromatographic separation was performed by using an Inertsil ODS-4
      column, with methanol and water containing ammonium acetate as the mobile phase.
      Detection was carried out on a tandem mass spectrometer with electrospray
      ionization in the negative mode. Average recoveries from bovine muscle, bovine
      liver, bovine fat, swine muscle, salmon, eel, freshwater clam, egg, milk, and
      honey spiked at 0.0005-0.001 mg/kg were in the range of 79-108%, and the relative
      standard deviations were 2-8%. The limits of quantitations of the developed
      method were 0.0005 mg/kg for brodifacoum, 0.001 mg/kg for warfarin,
      coumatetralyl, and bromadiolone.

PMID- 21873816
TI  - [Multiresidue analysis of PCB, organochlorine pesticides and chlordanes in marine
      products by GC-micro ECD].
AB  - A multiresidue method using dual-injection, dual-column, and dual-micro electron
      capture detection gas chromatography (dual-column GC-uECD) was developed for the
      determination of PCB, organochlorine pesticides and chlordanes in marine
      products. The sample was extracted with hexane-acetone (2 : 1), and the extract
      was cleaned up by gel permeation chromatography(GPC)/solid-phase extraction
      (SPE). The GPC fraction was selectively collected, and loaded directly onto a
      graphitized carbon/PSA 2-layered column. After fractionation by 4% hydrated
      silica-gel column chromatography, each fraction was determined by dual-column GC
      uECD. Recoveries of PCB, organochlorine pesticides and chlordanes were in the
      ranges of 84-109% (RSD <= 21.6%), 74-117% (RSD <= 14.6%) and 69-114% (RSD <=
      12.9%), respectively. This method is superior to single chromatography for the
      determination of total PCB, and should be useful for monitoring of these
      pollutants in marine products.

PMID- 21873817
TI  - [Examination of original plant of mulberry bark extract, a natural food additive,
      based on composition of the constituents].
AB  - Mulberry bark extract, a natural food additive, is described as a "root bark
      extract from Morus bombycis" (Japanese name: Yamaguwa) in the Notice (1996)
      relating to existing food additives used in Japan. The results of analyses by
      LC/UV and LC/MS suggested that the Mulberry bark extract products that were
      tested were actually made from the root bark of Morus alba (Japanese name:
      Maguwa) or its hybrid species, because the compositions of the constituents in
      the products are more similar to those in the extracts of the dried root bark of
      M. alba and hybrid species that are cultivated in Japan than to those of M.
      bombycis. In addition, the constituents of the food additive products were
      different from those of the natural medicine Mori Cortex products ('Souhakuhi' in
      Japanese) made from the root bark of mulberry grown in China, and which is
      described as being derived from M. alba in the Japanese pharmacopoeia. These
      results were also corroborated by Principal Component Analysis using the peak
      areas of LC/MS analysis as explanatory variables. After this study, it was
      decided that Mulberry bark extract is one of the existing food additives that
      should be excluded from the list this year in Japan.

PMID- 21873818
TI  - Interlaboratory validation of quantitative duplex real-time PCR method for
      screening analysis of genetically modified maize.
AB  - To reduce the cost and time required to routinely perform the genetically
      modified organism (GMO) test, we developed a duplex quantitative real-time PCR
      method for a screening analysis simultaneously targeting an event-specific
      segment for GA21 and Cauliflower Mosaic Virus 35S promoter (P35S) segment [Oguchi
      et al., J. Food Hyg. Soc. Japan, 50, 117-125 (2009)]. To confirm the validity of
      the method, an interlaboratory collaborative study was conducted. In the
      collaborative study, conversion factors (Cfs), which are required to calculate
      the GMO amount (%), were first determined for two real-time PCR instruments, the
      ABI PRISM 7900HT and the ABI PRISM 7500. A blind test was then conducted. The
      limit of quantitation for both GA21 and P35S was estimated to be 0.5% or less.
      The trueness and precision were evaluated as the bias and reproducibility of the
      relative standard deviation (RSD(R)). The determined bias and RSD(R) were each
      less than 25%. We believe the developed method would be useful for the practical
      screening analysis of GM maize.

PMID- 21873820
TI  - [Helicobacter pylori eradication therapy in Korea].
AB  - Helicobacter pylori (H. pylori) is known to be associated with many
      gastrointestinal diseases including peptic ulcer. In Korea, eradication of H.
      pylori is recommended for peptic ulcer disease, low grade gastric mucosa
      associated lymphoid tissue lymphoma, and early gastric cancer. Standard triple
      therapy using proton pump inhibitor, clarithromycin, and amoxicillin and bismuth
      containing quadruple therapy have been the main first-line and second-line
      therapy for H. pylori in Korea. Although eradication rate of second-line
      quadruple therapy remains similar to that of the past, the success rate of
      eradication with triple therapy has decreased with increasing antimicrobial
      resistance to H. pylori. There is no standard third-line therapy, and some
      regimens that incorporate levofloxacin, moxifloxacin, and rifabutin can be used.
      New regimens such as sequential or concomitant therapy are suggested as
      alternative treatment for H. pylori. We need more well designed randomized
      controlled studies to choose proper treatment for H. pylori infection.

PMID- 21873821
TI  - [Primary antibiotic resistance of Helicobacter pylori strains and eradication
      rate according to gastroduodenal disease in Korea].
AB  - BACKGROUND/AIMS: This study was performed to evaluate whether the prevalence
      rates of primary antibiotic resistance in Helicobacter pylori (H. pylori)
      isolates and the eradication rate of H. pylori could be different between cancer
      and non-cancer patients. METHODS: H. pylori were isolated from gastric mucosal
      biopsy specimens obtained from 269 Koreans, who did not have any eradication
      therapy history and were diagnosed as one of the following diseases; chronic
      gastritis, benign gastric ulcer, duodenal ulcer or gastric cancer. The
      susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin,
      metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and
      moxifloxacin were examined with the agar dilution method. In addition,
      eradication rate of H. pylori was evaluated. RESULTS: There was no significant
      difference in the primary antibiotic resistance to above eight antibiotics among
      chronic gastritis, peptic ulcer disease and gastric cancer. Furthermore there was
      no difference of antibiotic resistance between cancer and non-cancer patients,
      and there was no difference of eradication rate of H. pylori according to
      disease. CONCLUSIONS: Primary antibiotic resistance and H. pylori eradication
      rate were not different between cancer and non-cancer patients.

PMID- 21873822
TI  - [Shifting in seroprevalence of HBsAg and anti-HCV during recent 10 years in
      adults resident in Daegu and Gyeongbuk province].
AB  - BACKGROUND/AIMS: There have been only few studies on the population-adjusted
      seroprevalence of HBV and HCV and on the change of them for more than 10 years in
      Korea. Therefore, this study was performed to evaluate them at a single health
      center in Daegu and Gyeongbuk province considering the population composition
      ratio. METHODS: We analyzed the seromarkers of HBV and HCV of 6,237 randomly
      sampled adults who had received health screening at the health promotion center
      in Dongsan hospital during the periods from year 1997 to 1999 (Period A) and from
      2007 to 2009 (Period B). RESULTS: The seroprevalences of HBsAg, anti-HBs, anti
      HBc and anti-HCV were 4.8%, 70.2%, 47.4%, and 0.5%, respectively. There is no
      difference in the seroprevalence of HBsAg between period A and B. However,
      downward tendency of prevalence through A to B from 6.8% to 4.5% could be found
      in 40s, and upward tendency from 4.7% to 6.8% in 50s. As for the seroprevalence
      of anti-HCV, although there was no difference through A to B, for 50s, it
      decreasd from 2.0% to 0.3% (p=0.007). However, for 60s, it increased as much as
      decreasd for 50s. CONCLUSIONS: The seroprevalence of HBsAg in Daegu/Gyeongbuk
      province was 4.8% and showed no difference through the time period of 10 years.
      The seroprevalence of anti-HCV was 0.5% and also showed no difference through the
      time periods.

PMID- 21873823
TI  - [A single institution's experience of endoscopic retrograde
      cholangiopancreaticography in the eldery patients: outcomes, safety and
      complications].
AB  - BACKGROUND/AIMS: As the population ages, endoscopic retrograde
      cholangiopancreaticography (ERCP) is being used increasingly as a diagnostic and
      therapeutic tool for elderly patients with pancreatobiliary disease. The aim of
      this study was to assess the outcomes, safety and complications associated with
      ERCP performed in the elderly patients. METHODS: We retrospectively reviewed the
      medical record of 596 patients who were 50 years of age or older and underwent
      ERCP from January 2005 to September 2010. The patients were classified into two
      groups according to the age: non-elderly, 50-74 years old and elderly, >=75 years
      old. Comparisons were made between two groups. RESULTS: Five hundred and ninety
      six patients (132 elderly and 464 non-elderly patients) were enrolled. The
      success rate of ERCP was 89.4% in the elderly and 91.9% in the non-elderly. The
      major complications were occurred in 11 patients of the elderly and 16 of the non
      elderly, and the complication rate was significantly higher in the elderly
      compared to the non-elderly (8.3% vs. 3.4%, p=0.011). Pancreatitis occurred in 2
      elderly patients and 10 non-elderly patients (1.5% vs. 2.1%, p=1.0). There was a
      higher rate of bleeding in the elderly patients (4.5% vs. 1.3%, p=0.01).
      CONCLUSIONS: ERCP is effective and safe even in elderly patients. Outcomes of
      diagnostic and therapeutic ERCP in the elderly patients were similar to those in
      non-elderly patients. Elderly patients undergoing ERCP carried similar risk of
      pancreatitis but a higher risk of bleeding and perforation compared to non
      elderly patients.

PMID- 21873824
TI  - Lack of radiation protection for endoscopists performing endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND/AIMS: ERCP using fluoroscopy should be practiced with an adequate
      radiation protection. However, the awareness of gastrointestinal endoscopists to
      radiation protection was considered insufficient. In Korea, a country with a
      rapid increase the number of ERCP procedures, there is no data about radiation
      protection practices for gastrointestinal endoscopists. The purpose of this study
      was to investigate current clinical practices and the awareness on radiation
      protection in ERCP performing physicians in Korea. METHODS: An anonymous
      questionnaire regarding radiation protection practices was mailed to 100 members
      of Korean Pancreatobiliary Association who was porforming ERCP. The questionnaire
      included ERCP volume of each endoscopist, use of protection devices such as
      apron, thyroid shield, lead glasses and any mobile shield for scattered
      radiation, and whether they monitored their own radiation exposure dosage.
      RESULTS: All respondents wore lead aprons during ERCP. While 52.5% of
      endoscopists answered that they always wear thyroid guards, 26.9% rarely or never
      wore it. Only 14% wore lead glasses during the procedure and 69% never wore it.
      The preparation rates of mobile shields or lead curtains were only 14% and 24%,
      respectively. Only 10% of endoscopists attached an X-ray badge and 66.7% never
      used it. Moreover, 75% of endoscopists responded that they did not monitor their
      own exposure dose to radiation during ERCP. CONCLUSIONS: The lack of radiation
      protection of ERCP endoscopists in Korea was seemed serious. Awareness of
      radiation hazard should be more concerned and educated in parallel with the
      preparation of radiation protection equipments.

PMID- 21873825
TI  - [A case of chemical colitis caused by hydrogen peroxide enema].
AB  - Hydrogen peroxide is commonly used as a disinfectant that has been reported to
      cause chemical colitis. We report a case of 49 year-old man who presented with
      chemical colitis caused by self-inflicted hydrogen peroxide enema. In the
      sigmoidoscopic examination, diffuse erythematous and edematous mucosal change
      with multiple ulcerations and easy touch bleeding was noted from the rectum to
      the proximal sigmoid colon. Abdominal computed tomography showed diffuse wall
      thickening of the rectum and the sigmoid colon with inflammatory and reactive
      change at surrounding. The patient was treated with NPO, intravenous fluid, and
      antibiotic therapy. On 5th hospital day, abdominal pain and bloody stool
      disappeared, and the patient started oral feeding. He discharged on 6th hospital
      day with fully recovered state.

PMID- 21873826
TI  - [Crohn's disease presenting with erythema nodosum as an early sign: a case
      report].
AB  - Erythema nodosum is the most common form of septal panniculitis and the most
      frequent skin manifestation associated with inflammatory bowel disease, affecting
      up to 15% of Crohn's disease patients. Since the development of erythema nodosum
      is closely related with a variety of disorders and condition, it can serve as an
      important early sign of systemic disease. Here, we present the occurrence of
      erythema nodosum as an early sign of Cronh's disease in a 16-year-old woman.

PMID- 21873827
TI  - [A case of pegylated interferon alpha-2a monotherapy in a peritoneal dialysis
      patient with chronic hepatitis C].
AB  - Pegylated interferon (PEG-IFN) is now the standard treatment for chronic
      hepatitis C. But, there are few reports about patients with end stage renal
      disease, and treatment protocol for HCV infection has not been determined,
      particularly in patients on peritoneal dialysis. We experienced a case of a
      peritoneal dialysis patient with chronic hepatitis C who was successfully treated
      with PEG-IFN monotherapy. A 50-year old man was undergoing peritoneal dialysis
      because of diabetic nephropathy. Considering that his HCV genotype was 2, we
      decided to treat him with PEG-IFN alpha-2a monotherapy 4 month after the
      beginning of peritoneal dialysis. We adopted a 90 mg of PEG-IFN administration.
      After the injection of PEG-IFN, dialysate concentration of PEG-IFN did not change
      significantly. HCV-RNA disappeared at the 4th week and sustatined virus response
      was achieved thereafter. No side effects were observed during the treatment of 24
      weeks. PEG-IFN monotherapy with dose modification may be a safe and effective
      treatment for HCV infection in patients undergoing peritoneal dialysis.

PMID- 21873828
TI  - [A case of Chlamydia trachomatis peritonitis mimicking tuberculous peritonitis].
AB  - Lymphocytic ascites with low serum-ascites albumin gradient (SAAG) are observed
      mainly in tuberculous peritonitis, peritoneal carcinomatosis, and pancreatic
      disease. However, pelvic inflammatory disease (PID) induced generalized
      peritonitis causing diffuse ascites has been rarely described. We report a 26
      year old female patient, who was diagnosed as generalized peritonitis with
      diffuse ascites due to Chlamydia trachomatis infection. Gynecologic examination
      did not show the clue of PID and in the analysis of ascites, low SAAG,
      predominant lymphocyte count and high level of adenosine deaminase were noted.
      Although the best impression was tuberculous peritonitis on the base of these
      findings, the laparoscopic finding was consistent with PID and the PCR for C.
      trachomatis infection in cervical swab was positive. This case suggests that C.
      trachomatis peritonitis should be considered as a rare cause of low SAAG and
      lymphocytic ascites in sexually active women and should be intensively evaluated
      including laparoscopic examination.

PMID- 21873829
TI  - [Localized gastric amyloidosis].

PMID- 21873831
TI  - Thyroid hormones and depression: the Health in Men study.
AB  - CONTEXT: Current practice guidelines suggest that thyroid function tests should
      be an integral part of the assessment of adults presenting with a depressive
      episode, although there is a paucity of data available to support such a
      recommendation. OBJECTIVE: To determine if biochemical markers of thyroid
      dysfunction are associated with prevalent and incident clinically significant
      depressive symptoms. DESIGN: Cross-sectional and cohort studies. PATIENTS:
      Community-dwelling sample of 3,932 men age 69 to 87 free of overt thyroid
      disease. MAIN OUTCOME MEASURES: We used the 15-item Geriatric Depression Scale to
      ascertain the presence of prevalent clinically significant depressive symptoms,
      and the Western Australia Data Linkage System to establish the onset of a
      depressive episode according to the International Classification of Diseases.
      RESULTS: The serum concentration of thyroid-stimulating hormone and free
      thyroxine (fT4) did not affect the odds of prevalent or the hazard of incident
      depression. The odds of prevalent depression were 0.8 (95% CI: = 0.5-1.3) for men
      with subclinical hypothyroidism and 1.4 (95% CI: = 0.3-5.8) for those with
      subclinical hyperthyroidism. The hazard ratio of incident depression associated
      with subclinical hypothyroidism was 0.7 (95% CI: = 0.3-1.9). No men with
      subclinical hyperthyroidism developed depression during the follow-up period of
      5.5 +/- 1.4 years. CONCLUSIONS: Subclinical thyroid disease is not associated
      with prevalent or incident depression in older men. These findings do not support
      the routine screening of subclinical thyroid dysfunction among older adults with
      depression.

PMID- 21873833
TI  - Age and gender but not common chronic illnesses predict odor identification in
      older African Americans.
AB  - OBJECTIVES: Loss of smell accompanies specific neurodegenerative diseases and may
      facilitate the early detection of these. Smell deficiency also engenders safety
      risks in the elderly. The Brief Smell Identification Test (BSIT), though
      clinically practical, is accompanied by limited normative data, and none for
      minority subjects. We sought to improve the clinical utility of the BSIT by
      determining the relationship between test score, demographics, and chronic
      illnesses in a minority cohort. DESIGN: We evaluated BSIT performance in a cohort
      of cognitively healthy older African Americans and compared our findings with all
      existing data for the test. SETTING: General community. PARTICIPANTS: African
      Americans (N = 288) age 55-87 years living independently. MAIN OUTCOME MEASURE:
      BSIT score stratified by demographic predictors. RESULTS: Age and gender were
      predictive of score, but education, global cognition, hypertension, diabetes, and
      thyroid disorder were not significantly related to performance within this
      cognitively healthy sample. Comparison of our findings with international studies
      suggests reasonably consistent performance levels across diverse samples.
      CONCLUSIONS: The lack of a significant relationship between common chronic
      conditions, or sociocultural factors, with the BSIT score underscores the value
      of this test in screening for odor identification deficiencies in older subjects.

PMID- 21873832
TI  - Amygdala volume in late-life depression: relationship with age of onset.
AB  - OBJECTIVES: Depression is common in the elderly population. Although numerous
      neuroimaging studies have examined depressed elders, there is limited research
      examining how amygdala volume may be related to depression. DESIGN: A cross
      sectional examination of amygdala volume comparing elders with and without a
      diagnosis of major depressive disorder, and between depressed subjects with early
      and later initial depression onset. SETTING: An academic medical center.
      PARTICIPANTS: Ninety-one elderly patients meeting Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, criteria for major depression (54
      early-onset depressed and 37 late-onset depressed) and 31 elderly subjects
      without any psychiatric diagnoses. MEASUREMENTS: Amygdala and cerebral volumes
      were measured using reliable manual tracing methods. RESULTS: In models
      controlling for age, sex, and cerebral volume, there was a significant difference
      between diagnostic cohorts in amygdala volume bilaterally (left: F[2, 116] =
      16.28, p < 0.0001; right: F[2, 116] = 16.28, p < 0.0001). Using least squares
      mean group analyses, both early- and late-onset depressed subjects exhibited
      smaller bilateral amygdala volumes than did the nondepressed cohort (all
      comparisons p < 0.0001), but the two depressed cohorts did not exhibit a
      statistically significant difference. LIMITATIONS: Limitations include missing
      antidepressant treatment data, recall bias, inability to establish a causal
      relationship between amygdala size and depression given the cross-sectional
      nature of the design. CONCLUSIONS: Depression in later life is associated with
      smaller amygdala volumes, regardless of age of initial onset of depression.

PMID- 21873834
TI  - Depressive symptoms and functional transitions over time in older persons.
AB  - OBJECTIVE: The authors determined the association between clinically significant
      depressive symptoms, often referred to as depression, and subsequent transitions
      between no disability, mild disability, severe disability, and death. DESIGN:
      Prospective cohort study. SETTING: General community in greater New Haven,
      Connecticut, from March 23, 1998, to December 31, 2008. PARTICIPANTS: Seven
      hundred fifty-four persons, age 70 years or older. MEASUREMENTS: Monthly
      assessments of disability in essential activities of daily living and assessments
      of depressive symptoms every 18 months using a short-form of the Center for
      Epidemiologic Studies of Depression Scale for up to 129 months. RESULTS:
      Depressed participants were more likely than those who were nondepressed to
      transition from a state of no disability to mild (HR = 1.52; 95% CI: 1.25-1.85)
      and severe disability (HR = 1.57; 95% CI: 1.22-2.01), and from a state of mild
      disability to severe disability (HR = 1.33; 95% CI: 1.06-1.65), and were less
      likely to transition from a state of mild disability to no disability (HR = 0.69;
      95% CI: 0.57-0.85) and from a state of severe disability to no disability (HR =
      0.50; 95% CI: 0.31-0.79). CONCLUSIONS: Depressive symptoms are associated with
      transitions into and out of disabled states and with increased likelihood of
      transitioning from mild to severe disability. More broadly, our findings
      underscore the complexity of the relationship between depressive symptoms and
      disability. Future work is needed to evaluate the likely reciprocal relationship
      between depression and functional transitions in older persons.

PMID- 21873836
TI  - Effects of cholinesterase inhibitors on postoperative outcomes of older adults
      with dementia undergoing hip fracture surgery.
AB  - OBJECTIVES: Cholinesterase inhibitors (ChEIs) may interact with muscle relaxants
      given during general anesthesia (GA), increasing the risk of postoperative
      complications. We evaluated the effects of ChEIs on the postoperative outcomes of
      older adults who underwent hip fracture surgery. DESIGN: Population-based cohort
      study using linked administrative databases. PARTICIPANTS: All individuals with
      dementia age 66 years or older, who underwent hip fracture surgery between April
      1, 2003, and December 31, 2007, in Ontario, Canada. EXPOSURES: Use of any ChEI
      (donepezil, rivastigmine, or galantamine) before surgery. OUTCOMES: The primary
      composite outcome included any of the following: 30-day postoperative mortality;
      intensive care unit admissions; or in-hospital resuscitation. Secondary outcomes
      included postoperative respiratory failure and pneumonia. ANALYSIS: We stratified
      the study sample on the basis of residence (community or long-term care [LTC])
      and type of anesthetic (general or regional) to create four residence/anesthesia
      groups. We used propensity scores to match users and nonusers of ChEIs within the
      residence/anesthesia strata. We then calculated the relative risks (RR) and 95%
      confidence intervals (CI) for outcomes associated with ChEIs in the matched
      groups. RESULTS: A total of 624 pairs of individuals from the community and 725
      pairs from LTC were created among individuals who received GA. High rates of
      postoperative mortality and complications were observed in both ChEI users and
      nonusers. The RR of the primary outcome associated with ChEI use for individuals
      receiving GA was 0.88 (95% CI: 0.68-1.16; chi2 = 0.93; df = 1; p = 0.34) and 0.82
      (95% CI: 0.63-1.04; chi2 = 2.59; df = 1; p = 0.11) in the community and LTC
      groups, respectively. In addition, ChEIs were not associated with any significant
      increased risk of postoperative respiratory complications. CONCLUSIONS: ChEI use
      was not associated with an increased risk of postoperative complications among
      older adults with dementia who underwent hip fracture surgery. However, the poor
      postoperative outcomes overall reinforced the need to prevent fractures and
      improve outcomes in this population.

PMID- 21873835
TI  - Differences in verbal memory performance in postmenopausal women receiving
      hormone therapy: 17beta-estradiol versus conjugated equine estrogens.
AB  - OBJECTIVE: Much controversy exists and many questions remain unanswered about the
      effects of hormone therapy (HT) on cognition in postmenopausal women. There is
      growing evidence suggesting that HT compounds containing conjugated equine
      estrogen (CEE) have negative effects on cognition whereas 17beta-estradiol
      (17beta-E) either has positive or neutral effects. The present study sought to
      further examine this issue in a sample of postmenopausal women with risk factors
      for Alzheimer's disease (AD). DESIGN: Cross-sectional neuropsychological
      evaluation. SETTING: Academic research clinic. PARTICIPANTS: 68 healthy
      postmenopausal women (aged 49-68) receiving either 17beta-E or CEE for at least
      one year with increased risk for AD. MEASUREMENTS: Neuropsychological test
      battery of the cognitive domains of attention/working memory/processing speed,
      verbal memory, visual memory, and executive functioning. RESULTS: Multivariate
      analyses of variance (MANOVA) showed significantly better verbal memory
      performance in women receiving 17beta-E compared to women receiving CEE
      regardless of age, IQ, years of education, risk factors for AD (including APOE
      epsilon4 carriership), duration of endogenous and exogenous estrogen exposure,
      concurrent progesterone use, or natural versus surgical menopause status.
      CONCLUSIONS: Verbal memory performance was better in postmenopausal women
      receiving 17beta-E compared to CEE in a sample population of women with risk
      factors for AD. Genetic risk for AD as well as other confounds did not affect
      this finding. The results suggest a differential effect of HT type on verbal
      memory, with 17beta-E being a preferential compound. Further evaluation of HT
      types, regimens and duration of use on cognitive performance in postmenopausal
      women in a controlled longitudinal design is warranted.

PMID- 21873837
TI  - Early parental death and remarriage of widowed parents as risk factors for
      Alzheimer disease: the Cache County study.
AB  - OBJECTIVES: Early parental death is associated with lifelong tendencies toward
      depression and chronic stress. We tested the hypothesis that early parental death
      is associated with higher risk for Alzheimer disease (AD) in offspring. DESIGN: A
      population-based epidemiological study of dementia with detailed clinical
      evaluations, linked to one of the world's richest sources of objective
      genealogical and vital statistics data. SETTING: Home visits with residents of a
      rural county in northern Utah. PARTICIPANTS: 4,108 subjects, aged 65-105.
      MEASUREMENTS: Multistage dementia ascertainment protocol implemented in four
      triennial waves, yielding expert consensus diagnoses of 570 participants with AD
      and 3,538 without dementia. Parental death dates, socioeconomic status, and
      parental remarriage after widowhood were obtained from the Utah Population
      Database, a large genealogical database linked to statewide birth and death
      records. RESULTS: Mother's death during subject's adolescence was significantly
      associated with higher rate of AD in regression models that included age, gender,
      education, APOE genotype, and socioeconomic status. Father's death before subject
      age 5 showed a weaker association. In stratified analyses, associations were
      significant only when the widowed parent did not remarry. Parental death
      associations were not moderated by gender or APOE genotype. Findings were
      specific to AD and not found for non-AD dementia. CONCLUSIONS: Parental death
      during childhood is associated with higher prevalence of AD, with different
      critical periods for father's versus mother's death, with strength of these
      associations attenuated by remarriage of the widowed parent.

PMID- 21873838
TI  - Association between tryptophan hydroxylase-2 gene and late-onset depression.
AB  - OBJECTIVE: The aim of this study was to examine the association between
      polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset
      depression (LOD) in the Brazilian population. METHODS: We genotyped 8 tag SNPs in
      the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the
      comparison group to investigate an association between the TPH2 gene and LOD.
      RESULTS: Our findings suggested an association between tag SNP rs4565946
      heterozygous C/T (p = 0.034; chi2 = 6.7; df = 2) and decreased risk of LOD. The
      tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; chi2 = 7.3; df = 2) and
      increase risk of LOD and allelic association of ancestral allele A and increase
      risk of LOD was demonstrated (p = 0.005; chi2 = 7.8; df = 1). CONCLUSION: We
      found the statistically significant association between two tag SNPs and LOD. Our
      results support the hypothesis that the TPH2 gene is associated with LOD.

PMID- 21873841
TI  - Fathers' role in protecting children.

PMID- 21873842
TI  - Understanding post-hire transitional challenges of foreign-educated nurses.

PMID- 21873843
TI  - The impact of RN-UAP relationships on quality and safety.

PMID- 21873844
TI  - The gap between education preferences and hiring practices.

PMID- 21873846
TI  - Power up your staffing model with patient acuity.
AB  - Plug into a more detailed picture of nursing workload to reduce hospital expenses
      while providing quality nursing care with an effective staff.

PMID- 21873847
TI  - Are you a transformational leader?

PMID- 21873848
TI  - Foster cultural responsiveness on your unit.
AB  - As patient populations become more diverse, the challenge for nurse managers to
      ensure delivery of individualized, patient-centered care intensifies. Every
      patient presents with unique healthcare beliefs, values, behaviors, and lived
      experiences, and their culture shapes and influences health decisions and
      perceptions of healthcare encounters. Although cultural responsiveness resources
      and capabilities are influenced by a health organization's leaders and policies,
      they're directly implemented by nurse managers, nurses, and staff in each patient
      and family interaction. Equipping your staff with cultural responsiveness
      knowledge and skills, and helping them to internalize and consistently
      demonstrate culturally responsive behaviors, will improve patient satisfaction
      and quality care outcomes on your unit.

PMID- 21873849
TI  - Navigating the clinical practicum; making a case for Magnet(r).

PMID- 21873851
TI  - The utility of the "bull's-eye" artifact on breast elasticity imaging in reducing
      breast lesion biopsy rate.
AB  - PURPOSE: The objectives of the study were to evaluate the accuracy of the "bull's
      eye" artifact of elasticity imaging (EI) in determining the benignity of cystic
      breast lesions and to determine the utility of such artifact in reducing the
      biopsy rate of the benign lesions. METHODS: This study was performed under local
      institutional review board supervision and was in compliance with the Health
      Insurance Portability and Accountability Act of 1996. A retrospective review of
      383 breast lesions from 309 consecutive patients undergoing diagnostic breast
      ultrasonography with EI (Siemens Antares or Siemens S2000; Siemens Healthcare,
      Mountain View, Calif) was conducted. The B-mode characteristics of those lesions
      determined whether biopsy was conducted. Pathological reports of the biopsied
      lesions were reviewed. Lesions demonstrating the bull's-eye artifact on EI were
      determined. The accuracy of the artifact in determining the benignity of cystic
      breast lesions was determined. RESULTS: Of the 383 lesions, 243 lesions were
      recommended for biopsy based on the B-mode characteristics (biopsy rate, 63.4%).
      Of those 243 lesions, 62 lesions demonstrated the bull's-eye artifact on EI, and
      all were confirmed benign cysts on pathological reports. Of the 181 lesions
      without the artifact, 116 were benign noncystic lesions, and 65 were malignant
      noncystic lesions. Hence, within the biopsied lesions, the bull's-eye artifact
      had perfect sensitivity, specificity, and positive predictive value in
      determining pathologically proven benign cysts. If the artifact can be used as a
      criterion to exclude lesions from biopsy, then the biopsy rate will be 181
      (47.3%) of 383, significantly lower than the 63.4% biopsy rate without using this
      criteria (P < 0.001). CONCLUSIONS: The bull's-eye artifact seen on EI on Siemens
      ultrasonography equipment is a promising tool in the evaluation and
      characterization of benign breast cysts and has the potential to significantly
      reduce the amount of unnecessary breast biopsy.

PMID- 21873852
TI  - Safety of ultrasound-guided fine needle aspiration biopsy of neck lesions in
      patients taking antithrombotic/anticoagulant medications.
AB  - We examined records of patients who underwent ultrasound-guided fine needle
      aspiration biopsy (USGFNAB) of neck lesions to determine whether there was a
      significantly increased incidence of bleeding complications in patients on
      antithrombotic and/or anticoagulant (AT/AC) medications compared to patients not
      receiving AT/AC therapy. Our institutional review board approved this Health
      Insurance Portability and Accountability Act-compliant retrospective examination
      of patients' medical data without requiring informed consent. The records of 593
      patients (422 women and 171 men ranging from 18 to 91 years of age) who underwent
      USGFNAB of 788 total neck lesions over an 18-month period were reviewed to
      determine AT/AC medication used and evidence of USGFNAB-related bleeding
      complications. Of these, 144 patients (24.3%) were taking one or more AT/AC
      medications including aspirin, clopidogrel, heparin, and warfarin. The chi2 test
      was used to assess statistically significant differences in the incidence of
      USGFNAB-related bleeding complications between patients who were on daily AT/AC
      medications (test group) and patients who were not (control group). Six USGFNAB
      related hematomas (1.0%) occurred. Two hematomas developed in patients on AT/AC
      medications, and 4 hematomas developed in patients who did not take AT/AC
      medications (chi = 0.27, df = 1, P = 0.603). This study shows no statistically
      significant difference in the incidence of hematoma formation after USGFNAB of
      neck lesions in patients taking AT/AC medications compared to patients not taking
      AT/AC medications. On the basis of these data, there is no benefit, with regard
      to incidence of bleeding complications, to discontinuing AT/AC medications in
      patients undergoing USGFNAB of neck masses.

PMID- 21873853
TI  - Complicated cholecystitis: the complementary roles of sonography and computed
      tomography.
AB  - Acute cholecystitis is a common cause of abdominal pain in the Western world.
      Unless treated promptly, patients with acute cholecystitis may develop
      complications such as gangrenous, perforated, or emphysematous cholecystitis.
      Because of the increased morbidity and mortality of complicated cholecystitis,
      early diagnosis and treatment are essential for optimal patient care.
      Nevertheless, complicated cholecystitis may pose significant challenges with
      cross-sectional imaging, including sonography and computed tomography (CT).
      Interpreting radiologists should be familiar with the spectrum of sonographic
      findings seen with complicated cholecystitis and as well as understand the
      complementary role of CT. Worrisome imaging findings for complicated
      cholecystitis include intraluminal findings (sloughed mucosa, hemorrhage,
      abnormal gas), gallbladder wall abnormalities (striations, asymmetric wall
      thickening, abnormal gas, loss of sonoreflectivity and contrast enhancement), and
      pericholecystic changes (echogenic fat, pericholecystic fluid, abscess
      formation). Finally, diagnosis of complicated cholecystitis by sonography and CT
      can guide alternative treatments including minimally invasive percutaneous and
      endoscopic options.

PMID- 21873854
TI  - Battlefield applications for handheld ultrasound.
AB  - Combat medical care provides unique challenges and opportunities for military
      medical teams. The austerity of the environment severely limits access to many
      diagnostic and therapeutic tools. Because of their compact size, handheld
      ultrasound (US) machines are increasingly being used in these constrained
      environments. A growing body of literature documents the diagnostic utility of
      handheld US for trauma encountered in the battlefield. Furthermore, US guidance
      may assist in the performance of some procedures performed in battlefield medical
      care. This review will provide an overview of the history, current status,
      limitations and potential future of US utility for the battlefield.

PMID- 21873855
TI  - Elastography: current status, future prospects, and making it work for you.
AB  - Elastography has emerged as a useful adjunct tool for ultrasound diagnosis.
      Elastograms are images of tissue stiffness and may be in color, grayscale, or a
      combination of the two. The first and most common application of elastography is
      for the diagnosis of breast lesions where studies have shown an area under the
      receiver operating characteristic curve of 0.88 to 0.95 for distinguishing cancer
      from benign lesions. The technique is also useful for the diagnosis of complex
      cysts, although different scanners may vary in how they display such lesions.
      Recent advances in elastography include quantification using strain ratios,
      acoustic radiation force impulse imaging, and shear wave velocity estimation.
      These are useful not only for characterizing focal masses but also for diagnosing
      diffuse organ diseases such as liver cirrhosis. Other near term potential
      applications for elastography include characterization of thyroid nodules and
      lymph node evaluation for metastatic disease. Prostate cancer detection is also a
      potential application, but obtaining high-quality elastograms may be difficult.
      This area is evolving. Other promising applications include atheromatous plaque
      and arterial wall evaluation, venous thrombus evaluation, graft rejection, and
      monitoring of tumor ablation therapy. When contemplating the acquisition of a
      system with elastography in this rapidly evolving field, a clear picture of the
      manufacturer's plans for future upgrades (including quantification) should be
      obtained.

PMID- 21873856
TI  - Ultrasound of the placenta and umbilical cord: a review.
AB  - The placenta and umbilical cord play important roles in the development of the
      growing fetus. The placenta can be clearly identified by the 14th gestational
      week and should be evaluated during each obstetric ultrasound examination.This
      article reviews the formation of the placenta and its expected sonographic
      appearance throughout gestation along with its normal variants. Expected findings
      in a singleton pregnancy are primarily addressed. The next portion of the article
      covers placental abnormalities of clinical consequence, including anomalies of
      appearance, location, and function.The umbilical cord is also discussed, focusing
      on the relevance of the location of the umbilical cord's insertion into the
      placenta.

PMID- 21873877
TI  - ACR Appropriateness Criteria(r) Acute Pelvic Pain in the Reproductive Age Group.
AB  - Premenopausal women who present with acute pelvic pain frequently pose a
      diagnostic dilemma, exhibiting nonspecific signs and symptoms, the most common
      being nausea, vomiting, and leukocytosis. Diagnostic considerations encompass
      multiple organ systems, including obstetric, gynecologic, urologic,
      gastrointestinal, and vascular etiologies. The selection of imaging modality is
      determined by the clinically suspected differential diagnosis. Thus, a careful
      evaluation of such a patient should be performed and diagnostic considerations
      narrowed before a modality is chosen. Transvaginal and transabdominal pelvic
      sonography is the modality of choice when an obstetric or gynecologic abnormality
      is suspected, and computed tomography is more useful when gastrointestinal or
      genitourinary pathology is more likely. Magnetic resonance imaging, when
      available in the acute setting, is favored over computed tomography for assessing
      pregnant patients for nongynecologic etiologies because of the lack of ionizing
      radiation. The American College of Radiology Appropriateness Criteria are
      evidence-based guidelines for specific clinical conditions that are reviewed
      every two years by a multidisciplinary expert panel. The guideline development
      and review include an extensive analysis of current medical literature from peer
      reviewed journals and the application of a well-established consensus methodology
      (modified Delphi) to rate the appropriateness of imaging and treatment procedures
      by the panel. In those instances where evidence is lacking or not definitive,
      expert opinion may be used to recommend imaging or treatment.

PMID- 21873878
TI  - Imaging evaluation of acute pelvic pain in reproductive age women: what is the
      best study?

PMID- 21873879
TI  - ARA290, a peptide derived from the tertiary structure of erythropoietin, produces
      long-term relief of neuropathic pain: an experimental study in rats and beta
      common receptor knockout mice.
AB  - BACKGROUND: Exogenous erythropoietin inhibits development of allodynia in
      experimental painful neuropathy because of its antiinflammatory and
      neuroprotective properties at spinal, supraspinal, and possibly peripheral sites.
      The authors assess the effect of a nonhematopoietic erythropoietin analog,
      ARA290, on tactile and cold allodynia in a model of neuropathic pain (spared
      nerve injury) in rats and mice lacking the beta-common receptor (betacR mice), a
      component of the receptor complex mediating tissue protection. METHODS: Twenty
      four hours after peripheral nerve injury, rats and mice were injected with ARA290
      or vehicle (five 30-MUg/kg intraperitoneal injections at 2-day intervals,
      followed by once/week, n = 8/group). In a separate group of eight rats, ARA290
      treatment was restricted to five doses during the initial 2 weeks after surgery.
      RESULTS: In rats, irrespective of treatment paradigm, ARA290 produced effective,
      long-term (as long as 15 weeks) relief of tactile and cold allodynia (P < 0.001
      vs. vehicle-treated animals). ARA290 was effective in wild-type mice, producing
      significant relief of allodynia. In contrast, in betacR mice no effect of ARA290
      was observed. CONCLUSIONS: ARA290 produces long-term relief of allodynia because
      of activation of the beta-common receptor. It is argued that relief of
      neuropathic pain attributable to ARA290 treatment is related to its
      antiinflammatory properties, possibly within the central nervous system. Because
      ARA290, in contrast to erythropoietin, is devoid of hematopoietic and
      cardiovascular side effects, ARA290 is a promising new drug in the prevention of
      peripheral nerve injury-induced neuropathic pain in humans.

PMID- 21873880
TI  - Red cell distribution width and mortality: effect of left ventricular
      hypertrophy.

PMID- 21873882
TI  - A comparison of the effects of ketamine, chloral hydrate and pentobarbital sodium
      anesthesia on isolated rat hearts and cardiomyocytes.
AB  - OBJECTIVES: The study was intended to investigate which commonly used anesthetic
      in intact animals has the least effect on the function of isolated hearts and
      cardiomyocytes among the anesthetized animals. METHODS: The hearts of male
      Sprague-Dawley rats were removed after they were anesthetized with ketamine,
      chloral hydrate or pentobarbital sodium, respectively, or were cervically
      dislocated. They were mounted on a Langendorff shelf. Heart rate (HR), left
      ventricular systolic pressure (LVSP), and maximal rate of increase of left
      ventricular pressure (+dp/dt) were observed and recorded. Cell shorting amplitude
      and survival rate were detected in isolated cardiomyocytes. RESULTS: The
      application of ketamine and pentobarbital sodium led to a significant decrease in
      HR, LVSP and +dp/dt in isolated hearts. Furthermore, pentobarbital sodium
      inhibited cell shorting amplitude and reduced the survival rate of isolated
      cardiomyocytes. Chloral hydrate did not significantly alter HR, LVSP, +dp/dt,
      cell shorting amplitude and survival rate. CONCLUSION: The effects of anesthetics
      on cardiac parameters were considered when choosing an anesthesia administration.
      The results suggested that chloral hydrate as an anesthetic was appropriately
      applied for the studies of isolated hearts and cardiomyocytes.

PMID- 21873883
TI  - The invisible side of war: families caring for US service members with traumatic
      brain injuries and polytrauma.
AB  - OBJECTIVES: : To (1) identify informal caregivers to injured US service members
      following acute rehabilitation for polytraumatic injuries, principally traumatic
      brain injury (TBI), and (2) describe the prevalence and variation of care
      recipient and caregiver experiences. DESIGN: : Cross-sectional survey of
      caregivers. PARTICIPANTS: : Caregivers (N = 564) of service members with TBI who
      received inpatient rehabilitation care in a Veterans Affairs' Polytrauma
      Rehabilitation Center between 2001 and 2009. MAIN OUTCOME MEASURES: : Questions
      about caregiver and patient characteristics, type, and quantity of care currently
      being provided. RESULTS: : Caregiving responsibilities fall primarily on women
      (79%), typically a parent (62%) or spouse (32%). After a median 4 years since
      injury, 22% of patients still required assistance with activities of daily living
      and instrumental activities of daily living. An additional 48% required
      assistance with only instrumental activities of daily living. Nearly 25% of
      caregivers reported more than 40 h/wk of care and another 20% reported 5 to 40
      h/wk of care. Of caregivers providing assistance with activities of daily living,
      49% provided care >= 80 h/wk. Nearly 60% of caregivers were solely responsible
      for the caregiving. Most caregivers also reported providing other help, including
      managing emotions and navigating health and legal systems. CONCLUSIONS: :
      Caregivers who provide assistance with either activities of daily living or
      instrumental activities of daily living may need additional resources to meet the
      long-term needs of their injured family member.

PMID- 21873881
TI  - Relation between serum sodium levels and prognosis in outpatients with chronic
      heart failure: neutral effect of treatment with beta-blockers and angiotensin
      converting enzyme inhibitors: data from the Italian Network on Congestive Heart
      Failure (IN-CHF database).
AB  - INTRODUCTION: The predictive role of hyponatremia has been tested in acute and
      chronic heart failure. Sodium level is inversely related with renin-angiotensin
      aldersterone system (RAAS) and sympathetic nervous activity but important issues
      remain unresolved. Our aim was to define the level of hyponatremia able to
      predict 1-year outcomes and investigate the relation between sodium levels and
      mortality and the effect of beta-blockers and angiotensin-converting enzyme (ACE)
      inhibitors on this relation. METHODS: We analyzed 4670 patients enrolled in the
      IN-CHF Italian Registry. We controlled the predictivity of hyponatremia, testing
      it either as a continuous variable and dividing the study sample into three
      severity groups: group 1 (>=136  mEq/l; n = 4207), group 2 (131-135  mEq/l; n =
      389) and group 3 (<=130  mEq/l; n = 74). The linearity of the relationship
      between sodium levels and mortality was also tested. RESULTS: Mild-to-moderate
      and severe hyponatremia (groups 2 and 3) independently predicted the 1-year
      mortality. The relation between sodium concentration and death was not linear and
      a decrease of 1  mEq/l of sodium increased death rate only for values of sodium
      142.9  mEq/l or less. This relationship was not modified by beta-blocker and ACE
      inhibitor therapies. CONCLUSION: Our data confirm the negative prognostic value
      of hyponatremia, even of moderate degree, independently of the use of recommended
      treatments for heart failure.

PMID- 21873884
TI  - Enhanced endothelial progenitor cell angiogenic potency, present in early
      experimental renovascular hypertension, deteriorates with disease duration.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) augment neovascularization and
      repair of damaged tissues, but may undergo functional changes during exposure to
      cardiovascular risk factors. This study tested the hypothesis that early
      renovascular hypertension (RVH) modulates the temporal pattern of EPC function
      that deteriorates with disease duration. METHODS: RVH was induced in domestic
      pigs by unilateral renal artery stenosis. EPCs were cultured after 3, 6, and 12
      weeks of RVH or normal control to evaluate EPC function, growth factor, and
      homing receptor expression. Plasma renin activity (PRA), vascular endothelial
      growth factor (VEGF), and its soluble receptor-1 (sFlt-1) were measured in
      plasma. EPCs (10 * 10) isolated from 3-week RVH or from normal pigs were also
      injected into control kidneys (n = 6-7, each group), and 4 weeks later single
      kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were
      evaluated. Microvascular density was studied ex vivo using microcomputed
      tomography. RESULTS: Blood pressure peaked at 3 weeks and remained higher than
      normal throughout the study. Systemic PRA also peaked after 3 weeks of RVH and
      declined thereafter, whereas sFlt-1 showed a reciprocal pattern. In vivo, only
      RVH but not normal EPCs increased RBF, GFR, and microvascular density. RVH-EPCs
      showed in vitro enhanced proliferation, tube formation, VEGF, and homing receptor
      expression that peaked at 3 weeks, which were abolished by valsartan and returned
      to baseline levels after 12 weeks of RVH. EPC number remained unchanged
      throughout the study. CONCLUSION: A transient enhancement of EPC function,
      mediated by angiotensin II, may contribute to compensatory vascular adaptation in
      early RVH, but is lost as hypertension persists.

PMID- 21873885
TI  - Repeated exposures to moderately increased intravascular pressure increases
      stiffness in human arteries and arterioles.
AB  - OBJECTIVE: The aim was to investigate whether repeated exposures to moderate
      pressure elevations in the blood vessels of the arms (pressure training) affect
      pressure distension in arteries/arterioles of healthy individuals. METHODS:
      Pressure training and vascular pressure-distension determinations were conducted
      with the participant (n = 11) seated in a pressure chamber with one arm slipped
      through a hole in the chamber door. Intravascular pressure was increased by
      elevating chamber pressure. Before pressure training, one arm was investigated
      (control arm) during stepwise increases in chamber pressure to 180 mmHg. Diameter
      and flow were measured in the brachial artery using ultrasonography/Doppler
      techniques. Thereafter, the contralateral arm underwent pressure training
      consisting of fifteen 40-min sessions during 5 weeks; local intravascular
      pressures were elevated by 65-105 mmHg during the sessions. After pressure
      training, pressure-distension relationships were examined in both the trained arm
      and the control arm. RESULTS: Pressure training reduced (P < 0.01) arterial
      pressure distension by 46 +/- 18%. Likewise, the pressure-induced increase in
      arterial flow was less after (350 +/- 249%) than before (685 +/- 216%) pressure
      training. The pressure training-induced reductions in arterial/arteriolar
      pressure distension were reversed 5 weeks after pressure training. CONCLUSION:
      Thus, the in-vivo wall stiffness in arteries and arterioles increases markedly in
      response to intermittent, moderate increments of transmural pressure during 5
      weeks. The findings are compatible with the notion that local load serves as 'a
      prime mover' in the development of vascular changes in hypertension.

PMID- 21873886
TI  - Blood pressure variation in response to changing arm cuff height cannot be
      explained solely by the hydrostatic effect.
AB  - OBJECTIVE: To challenge the widely accepted explanation of hydrostatic effect for
      blood pressure (BP) variation in response to arm elevation by testing the
      hypothesis that SBP and DBP measurements in the same individual vary differently
      with cuff height, and to evaluate the potential deviation of these measurements
      from the value predicted by the hydrostatic theory. METHODS: Arm BP was measured
      in 37 individuals from the general population in the sitting position using a
      digital BP monitor. Measurements included nine consecutive BP readings at four
      cuff heights. The height dependence of BP was derived using reduced major axis
      regression. RESULTS: The variation in systolic and diastolic pressure had a
      highly linear correlation with cuff height (r =  -0.90 and -0.93, respectively),
      with the systolic rate lower than the diastolic one by -0.13 +/- 0.20 mmHg/cm (P
      = 0.0003) for all individuals. Systolic and diastolic rates were more negative in
      hypertensive individuals (P < 0.001 and P < 0.05, respectively). Significant
      deviation from the hydrostatic prediction of -0.77 mmHg/cm was observed in 30% of
      the individuals. CONCLUSION: This study assesses for the first time the
      inappropriateness of the hydrostatic theory as the sole explanation for the
      effect of gravity on BP. The phenomenon may be associated with mechanical
      properties of arteries in individuals known to have prognostic significance. The
      potential of the change in systolic and diastolic pressure with cuff height to be
      used as a novel type of clinical variable and vascular marker that can be
      determined by a simple test remains to be explored.

PMID- 21873887
TI  - Prognostic significance of a reduced glomerular filtration rate and interaction
      with microalbuminuria in resistant hypertension: a cohort study.
AB  - OBJECTIVE: The prognostic importance of a reduced glomerular filtration rate
      (GFR) is unsettled in resistant hypertension. The aim was to evaluate GFR and its
      interaction with microalbuminuria as prognostic predictors in resistant
      hypertensive patients. METHODS: In a prospective study, 531 resistant
      hypertensive patients had albuminuria measured and GFR estimated by Cockroft
      Gault (eGFRCG) and Modification of Diet in Renal Disease (MDRD; eGFRMDRD)
      equations. Primary endpoints were a composite of fatal and nonfatal
      cardiovascular events, all-cause and cardiovascular mortality. Multiple Cox
      regression assessed the associations between reduced GFR and endpoints, and
      interaction with microalbuminuria. RESULTS: After a median follow-up of 4.9
      years, 72 patients died, 42 from cardiovascular causes; and 96 cardiovascular
      events occurred. Decreasing grades of eGFRMDRD were predictors of the composite
      endpoint with hazard ratios of 2.1 [95% confidence interval (CI) 1.1-3.8], 2.2
      (1.2-3.9) and 3.5 (1.4-8.7) for the subgroups with eGFR between 60-89, 30-59 and
      less than 30 mg/min per 1.73 m, respectively. A decreased eGFRCG was predictive
      of the composite endpoint only in the lowest GFR subgroup (hazard ratio 2.7, 95%
      CI 1.0-7.1). The lowest eGFR subgroups were also associated with all-cause
      mortality, regardless of the estimated equation used. The presence of both
      reduced eGFR and microalbuminuria significantly increased cardiovascular risk in
      relation to one or another isolated, with hazard ratios of 3.0 (1.7-5.3), 2.9
      (1.5-5.5) and 4.6 (2.2-10.0), respectively for the composite endpoint, all-cause
      and cardiovascular mortality. CONCLUSION: A reduced GFR, mainly estimated by the
      MDRD equation, is an independent predictor of increased cardiovascular morbidity
      and mortality in resistant hypertension. The combination of a reduced GFR and
      increased albuminuria identifies patients with a very high cardiovascular risk.

PMID- 21873889
TI  - Subacute bilateral visual loss in methylmalonic acidemia.
AB  - A 23-year-old woman known to have methylmalonic acidemia (MMA) since birth
      suffered bilateral visual loss within 5 days. Multiple sclerosis, Leber
      hereditary optic neuropathy, vasculitis, infections (in particular treponema),
      and vitamin deficiency were ruled out. The optic nerve head changed from normal
      in appearance to atrophic. Treatment attempts with high-dose intravenous steroids
      and coenzyme Q10 combined with vitamin E were ineffective. The patient's
      underlying disease was metabolically well controlled by strict diet and carnitine
      supplementation. Toxic damage of both optic nerves due to MMA is the most likely
      mechanism. MRI showed moderate enhancement of both optic nerves. To our
      knowledge, this is the first report of a morphological correlate on MRI.

PMID- 21873888
TI  - CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow.
AB  - OBJECTIVE AND METHODS: A loss-of-function cytosine (C) for thymidine (T)
      transition at nucleotide 8590 of CYP4A11 has been associated with increased blood
      pressure in humans. We tested the hypothesis that CYP4A11 T8590C genotype is
      associated with salt sensitivity in the International Hypertensive Pathotype
      cohort. RESULTS: CYP4A11 T8590C genotype was associated with hypertension in
      whites. Among normotensive individuals, CYP4A11 T8590C genotype was associated
      with mean arterial pressure (MAP) during both high and low salt diets, such that
      there was no relationship between genotype and salt sensitivity of blood
      pressure. Among hypertensive individuals, CYP4A11 T8590C genotype did not
      associate with MAP during high salt intake, whereas MAP decreased with increasing
      number of C alleles during salt restriction. Consequently, among hypertensive
      individuals, change in MAP with salt restriction was greatest in individuals
      homozygous for the C allele (-10.9 +/- 9.9, -11.1 +/- 12.3, and -18.8 +/- 12.0
      mmHg in TT, CT, and CC groups, respectively, P = 0.02). In both normotensive and
      hypertensive individuals, individuals homozygous for the C allele exhibited an
      attenuated increase in renal blood flow during high salt. CYP4A11 genotype did
      not affect pressor responses to Angiotensin II in normotensive or hypertensive
      individuals. CONCLUSION: The loss-of-function CYP4A11 8590C allele is associated
      with a diagnosis of hypertension and, in normotensive individuals, with higher
      blood pressure regardless of salt intake. Among hypertensive individuals, the C
      allele is associated with salt-sensitive blood pressure. Impaired renal
      vasodilation during high salt intake may contribute to salt sensitivity. Studies
      are needed to determine whether CYP4A11 T8590C genotype predicts responses to
      medications that affect sodium homeostasis in hypertensive individuals.

PMID- 21873890
TI  - Convergent radioulnar translocation with radial head fracture in a child:  a case
      report and review of the literature.
AB  - SUMMARY: Convergent type radioulnar translocation is an extremely rare form of
      injury occurring in a growing child. We report a case of convergent radioulnar
      translocation along with a radial head fracture in a young child. Open reduction
      of the elbow and internal fixation of the radial head fragment helped in
      achieving concentric reduction and good functional outcome at 2 years of follow
      up. This case has been shown to highlight the diagnostic and management issues of
      this rare condition, which may be easily missed initially.

PMID- 21873891
TI  - Orthotopic liver transplantation for biliary atresia complicated by incidental
      cholangiocarcinoma.

PMID- 21873892
TI  - Prevalence and outcome of hepatobiliary dysfunction in neonatal septicaemia.
AB  - BACKGROUND: Cholestatic jaundice and liver enzyme abnormalities have been
      reported in neonatal septicaemia; the course, pattern, and outcome of such
      hepatobiliary dysfunction have not been described. METHODS: One hundred fifty
      three neonates with blood culture-positive sepsis were recruited from the
      neonatal intensive care unit of an urban hospital. Liver function tests were done
      on day 3 and day 10 in all of the cases. In babies with abnormal results (direct
      bilirubin >20% of total with a minimum level of 2/dL or alanine aminotransferase
      [ALT] >50  U/L), tests were repeated weekly for 1 month and then fortnightly for
      3 months or until normalization of values. Anthropometry was recorded at all of
      these visits. RESULTS: Klebsiella pneumoniae was the commonest organism, isolated
      in 95.4% of subjects. Eighty-three (54.2%) subjects had hepatobiliary dysfunction
      in the form of either cholestatic jaundice (n = 65 [42.5%]) or derangement in ALT
      (n = 57 [37.3%]). The onset of cholestasis was seen by day 3 of sepsis in 80% (n
      = 52), with maximum value of direct bilirubin seen by the 10th day in 90% (n =
      58). Only 15% (n = 10) continued to have cholestatic jaundice beyond 30 days of
      onset of sepsis, and it resolved by 60 days. Hepatic enzyme abnormalities
      followed a more protracted course: onset by day 10 in 95%, peak value by day 38
      in 90%, and normalisation by 60 days in 82% of subjects. The prevalence of any
      hepatobiliary dysfunction was found less frequently in babies who died as
      compared with survivors (43.4% vs 56.7%; P < 0.01). The weight, length, and head
      circumference during follow-up visits were comparable between neonates with or
      without hepatobiliary dysfunction. CONCLUSIONS: Hepatobiliary dysfunction is
      common in Gram-negative neonatal septicaemia. The onset of abnormalities is early
      in most cases but ultimately resolve within 2 to 3 months after sepsis. The
      presence of conjugated hyperbilirubinemia in neonatal sepsis may carry a better
      prognosis in terms of survival and has no significant effect on growth during
      early infancy.

PMID- 21873893
TI  - Bovine lactoferrin, human lactoferrin, and bioactivity.

PMID- 21873894
TI  - Heme oxygenase-1 is protective against nonsteroidal anti-inflammatory drug
      induced gastric ulcers.
AB  - OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the
      treatment of pain, fever, and inflammation. Long-term use of these drugs is
      associated with significant gastric injury. Activated neutrophils and oxidative
      stress seem to play a significant role in NSAID-induced gastric mucosal damage.
      The objective of our study is to examine the protective effects of an antioxidant
      and anti-inflammatory enzyme, heme oxygenase-1 (HO-1), in NSAID-induced gastric
      injury. METHODS: Mice were intraperitoneally injected with indomethacin (10
      mg/kg) or sham. A specific inducer of HO-1, cobalt protoporphyrin (5 mg/kg), was
      given 24 hours before indomethacin to allow for the expression of HO-1. Controls
      received sham treatment. Twenty-four hours after indomethacin injection, gastric
      tissue damage was examined with histology. HO-1 expression was measured with
      immunoblot; cytokine levels were measured with enzyme-linked immunosorbent assay.
      Neutrophil infiltration was quantified with myeloperoxidase assay. Using electron
      paramagnetic resonance and desferrioxamine, we measured the labile iron pool in
      the mouse stomach as a marker of oxidative stress. RESULTS: Indomethacin caused
      gastric inflammation and ulcers, neutrophil activation, and increased tissue
      expression of interleukin-6 and tumor necrosis factor-alpha in mice. Inducing HO
      1 with cobalt protoporphyrin reduced gastric inflammation, number of stomach
      ulcers, tissue neutrophil activation, and proinflammatory cytokine expression
      caused by indomethacin. CONCLUSIONS: These findings suggest that the induction of
      an anti-inflammatory and cytoprotective enzyme HO-1 may be a strategy to overcome
      the gastrointestinal adverse effects limiting the use of NSAIDs.

PMID- 21873895
TI  - Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of
      gastrointestinal and upper respiratory tract infections in infants.
AB  - OBJECTIVES: The aim of the study was to examine the effects of a follow-on
      formula containing Lactobacillus fermentum CECT5716 (L. fermentum) on the
      incidence of infections in infants between the ages of 6 and 12 months. PATIENTS
      AND METHODS: A randomized double-blinded controlled study including infants at
      the age of 6 months was conducted. Infants were assigned randomly to either
      follow-on formula supplemented with L. fermentum plus galactooligosaccharide
      (experimental group, EG), or the same formula supplemented with only
      galactooligosaccharide (control group, CG). The main outcome was the incidence of
      infections for the 6-month duration of the study. RESULTS: The EG showed a
      significant 46% reduction in the incidence rate (IR) of gastrointestinal
      infections (EG: 0.196 +/- 0.51, CG: 0.363 +/- 0.53, IR ratio 0.54, 95% confidence
      interval [CI] 0.307-0.950, P = 0.032), 27% reduction in the incidence of upper
      respiratory tract infections (EG: 0.969 +/- 0.96, CG: 1.330 +/- 1.23, IR ratio
      0.729, 95% CI 0.46-1.38, P = 0.026), and 30% reduction in the total number of
      infections (EG: 1.464 +/- 1.15, CG: 2.077 +/- 1.59, IR ratio 0.70, 95% CI 0.46
      1.38, P = 0.003), at the end of the study period compared with CG. CONCLUSIONS:
      Administration of a follow-on formula with L. fermentum CECT5716 may be useful
      for the prevention of community-acquired gastrointestinal and upper respiratory
      infections.

PMID- 21873896
TI  - Probiotics:  fishing in the ocean.

PMID- 21873897
TI  - Effects of in-season strength maintenance training frequency in professional
      soccer players.
AB  - The aim of the present study was to examine the effect of in-season strength
      maintenance training frequency on strength, jump height, and 40-m sprint
      performance in professional soccer players. The players performed the same
      strength training program twice a week during a 10-week preparatory period. In
      season, one group of players performed 1 strength maintenance training session
      per week (group 2 + 1; n = 7), whereas the other group performed 1 session every
      second week (group 2 + 0.5; n = 7). Only the strength training frequency during
      the in-season differed between the groups, whereas the exercise, sets and number
      of repetition maximum as well as soccer sessions were similar in the 2 groups.
      The preseason strength training resulted in an increased strength, sprint, and
      jump height (p < 0.05). During the first 12 weeks of the in-season, the initial
      gain in strength and 40-m sprint performance was maintained in group 2 + 1,
      whereas both strength and sprint performance were reduced in group 2 + 0.5 (p <
      0.05). There was no statistical significant change in jump height in any of the 2
      groups during the first 12 weeks of the in-season. In conclusion, performing 1
      weekly strength maintenance session during the first 12 weeks of the in-season
      allowed professional soccer players to maintain the improved strength, sprint,
      and jump performance achieved during a preceding 10-week preparatory period. On
      the other hand, performing only 1 strength maintenance session every second week
      during the in-season resulted in reduced leg strength and 40-m sprint
      performance. The practical recommendation from the present study is that during a
      12-week period, 1 strength maintenance session per week may be sufficient to
      maintain initial gain in strength and sprint performance achieved during a
      preceding preparatory period.

PMID- 21873898
TI  - A subsequent movement alters lower extremity muscle activity and kinetics in drop
      jumps vs. drop landings.
AB  - Drop landings and drop jumps are common training exercises and injury research
      model tasks. Drop landings have a single landing, whereas drop jumps include a
      subsequent jump after initial landing. With the expected ground impact, instant
      and landing surface suggested to modulate landing neuromechanics, muscle
      activity, and kinetics should be the same in both tasks when landing from the
      same height onto the same surface. Although previous researchers have noted some
      differences between these tasks across separate studies, little research has
      compared these tasks in the same study. Thus, we examined whether a subsequent
      movement after initial landing alters muscle activity and kinetics between drop
      landings and jumps. Fifteen women performed 10 drop landings and drop jumps each
      from 45 cm. Muscle onsets and integrated muscle activation amplitudes 150
      milliseconds before (preactivity) and after landing (postactivity) in the medial
      and lateral quadriceps, hamstrings, and lateral gastrocnemius and peak and time
      to-peak vertical ground reaction forces were examined across tasks (p <= 0.05).
      When performing drop jumps, subjects demonstrated later (p = 0.02) gastrocnemius
      and lesser lateral gastrocnemius (p = 0.002) and medial quadriceps (p = 0.02)
      preactivity followed by increased postactivity in all muscles (p = 0.006), with
      higher peak vertical ground reaction forces (p = 0.04) but no differences in
      times to these peaks (p = 0.60) than drop landings. The later gastrocnemius
      activation, higher gastrocnemius and quadriceps postlanding amplitudes, and
      higher ground reaction forces in drop jumps may allow subjects to propel the body
      vertically after the initial landing vs. simply absorbing impact in drop
      landings. Our results indicate that in addition to landing surface and height,
      anticipation of a subsequent task changes landing neuromechanics. Generalizations
      of results from landing-only studies should not be made with landing followed-by
      subsequent-activity studies. Landing exercises should be incorporated based on
      sport-specific demands.

PMID- 21873899
TI  - Using three-dimensional kinematics to identify feedback for the Snatch: a case
      study.
AB  - This case study evaluated the importance of peak bar velocity and starting
      posture adopted by a novice weightlifter to the outcome of a Snatch lift.
      Multiple observations of both successful and unsuccessful attempts were captured
      using 3D motion analysis (VICON MX: 500 Hz). The following data analysis was then
      used to derive feedback. In total, 133 attempts of loads ranging from 75 to 100%
      of 1 repetition maximum (1RM) were performed by the subject (age = 25 years,
      stature = 171 cm, mass = 74.8 kg, Snatch 1RM = 80 kg). Variables included peak
      bar velocity, pelvis, hip, knee and ankle joint angles at the starting position
      for the right side and the difference between (left minus right) sides. No main
      effects for load, success, or their interactions were found for peak bar
      velocity. Starting position kinematics were mostly nonsignificant between the
      outcome of Snatch attempts. Right ankle joint angle was the only exception, where
      unsuccessful attempts displayed greater (p = 0.0228) dorsiflexion. A more
      comprehensive finding was achieved through the partition modeling; this analysis
      provided valuable insight and coaching feedback for the subject in relation to
      his lower body kinematics at the starting position. Furthermore, the accuracy of
      this feedback was verified using a holdback data set. Specifically, anterior
      pelvic tilt (>17.6 degrees ) and hip joint (<89.6 degrees ) angle were identified
      as the key features to increasing the likelihood of success. In conclusion, this
      case study outlines a method of data collection and analysis to assist coaching
      feedback for an individual.

PMID- 21873900
TI  - Evaluation of circuit-training intensity for firefighters.
AB  - Firefighters are required to perform a variety of strenuous occupational tasks
      that require high levels of both aerobic and anaerobic fitness. Thus, it is
      critical that firefighters train at an appropriate intensity to develop adequate
      levels of aerobic and anaerobic fitness. Circuit training is a unique training
      method that stresses both energy systems and therefore may be a viable training
      method to enhance firefighter preparedness. Thus, the purpose of this study was
      to compare the aerobic and anaerobic intensities of a circuit-based workout to
      physiological data previously reported on firefighters performing fire
      suppression and rescue tasks. Twenty career firefighters performed a workout that
      included 2 rotations of 12 exercises that stressed all major muscle groups. Heart
      rate was recorded at the completion of each exercise. Blood lactate was measured
      before and approximately 5 minutes after the workout. The workout heart rate and
      post-workout blood lactate responses were statistically compared to data reported
      on firefighters performing fire suppression and rescue tasks. The mean circuit
      training heart rate was similar to previously reported heart rate responses from
      firefighters performing simulated smoke-diving tasks (79 +/- 5 vs. 79 +/- 6%
      maximum heart rate [HRmax], p = 0.741), but lower than previously reported heart
      rate responses from firefighters performing fire suppression tasks (79 +/- 5 vs.
      88 +/- 6% HRmax, p < 0.001). The workout produced a similar peak blood lactate
      compared to that when performing firefighting tasks (12 +/- 3 vs. 13 +/- 3
      mmol.L(-1), p = 0.084). In general, the circuit-based workout produced a lower
      cardiovascular stress but a similar anaerobic stress as compared to performing
      firefighting tasks. Therefore, firefighters should supplement low-intensity
      circuit-training programs with high-intensity cardiovascular and resistance
      training (e.g., >=85% 1-repetition maximum) exercises to adequately prepare for
      the variable physical demands of firefighting.

PMID- 21873901
TI  - Effect of strength training and the practice of Alpine skiing on bone mass
      density, growth, body composition, and the strength and power of the legs of
      adolescent skiers.
AB  - This work examines the influence of practicing strength training and Alpine
      skiing over 2 years on bone mineral density (BMD), growth, body composition, and
      the strength and power of the legs of adolescent skiers. The study subjects were
      20 adolescent skiers (10 girls and 10 boys) and 19 sedentary adolescents (9 girls
      and 10 boys), all 13-16 years of age. The BMDs of the lumbar column (L2-L4) and
      hip (neck of the femur, trochanter, and Ward's triangle) were determined by dual
      x-ray photon absorptiometry at the beginning and end of the experimental period.
      The increase in height and the percentage fat and muscular masses of the subjects
      were also recorded, as was their ability to jump (countermovement jump [CMJ]),
      their leg strength and power (squat test), and their leg anaerobic power
      (continuous jump test [CMJ15"]). No significant differences were seen in the
      increase in height, body weight, or percentage fat mass between the skiers and
      sedentary subjects, although the boy skiers showed a significant increase in
      percentage muscular mass (p < 0.05) compared to the sedentary boys. The
      improvement in the values of the different CMJ variables was significantly
      greater among the boy skiers than among the sedentary boys (p < 0.001-0.01). The
      same was true for the girls (p < 0.001), except for CMJ15". The skiers
      experienced a significantly greater increase in L2-L4 BMD than the sedentary
      subjects (boys p < 0.05; girls p < 0.01). These results suggest that Alpine
      skiing combined with rational strength training involves no special risk for the
      physical development of young people, has a positive effect on the power and the
      percentage of muscle mass in the legs, and helps to have a higher bone density in
      the lumbar spine (L2-L4).

PMID- 21873902
TI  - Kinetic analysis of several variations of push-ups.
AB  - Push-ups are a common and practical exercise that is used to enhance fitness,
      including upper body strength or endurance. The kinetic characteristics of push
      ups and its variations are yet to be quantified. Kinetic quantification is
      necessary to accurately evaluate the training load, and thus the nature of the
      training stimulus, for these exercise variations. This study assessed the peak
      vertical ground reaction forces (GRFs) of push-up variations including the
      regular push-up and those performed with flexed knee, feet elevated on a 30.48-cm
      box, and a 60.96-cm box, and hands elevated on a 30.48-cm box and a 60.96-cm box.
      Twenty-three recreationally fit individuals (14 men, 9 women) performed each of
      the 6 push-up variations in a randomized order. Peak GRF and peak GRF expressed
      as a coefficient of subject body mass were obtained with a force platform. Push
      ups with the feet elevated produced a higher GRF than all other push-up
      variations (p <= 0.05). Push-ups with hands elevated and push-ups from the flexed
      knee position produced a lower GRF than all other push-up variations (p <= 0.05).
      No gender differences in response to these push-up variations were found (p >
      0.05). Additionally, subject height was not related to the GRF for any of the
      push-up conditions (p > 0.05) other than the condition where hands were elevated
      on a 60.96-cm box (p <= 0.05; r = 0.63). These data can be used to progress the
      intensity of push-ups in a program and to quantify the training load as a
      percentage of body mass.

PMID- 21873903
TI  - Training specificity of hurdle vs. countermovement jump training.
AB  - The objective of this study was to compare bilateral and unilateral hurdle jumps
      with traditional countermovement jumps (CMJs). Thirteen athletes were tested
      during continuous forward bilateral and unilateral hurdle jumps and single CMJ.
      Countermovement jump height was used to establish the hurdle height. Subjects
      jumped forward over 4 hurdles with the force plate positioned after the second
      hurdle to measure vertical ground reaction force (VGRF), contact time (CT), and
      rate of force development (RFD). For bilateral jumps, hurdle height was
      established at maximal (100%) CMJ height and at 120, 140, and 160% of the CMJ
      height. The athletes were instructed to jump as fast as possible to mimic a
      training session drill. For unilateral jumps, hurdle height was set at 70, 80,
      and 90% of the CMJ height. Bilateral 160% jumps showed a significantly longer CT
      than bilateral 100, 120, and 140% jumps. The bilateral 100, 120, and 140% jumps
      had significantly shorter CT than the unilateral jumps and CMJ. The VGRF during
      bilateral jumps was higher than unilateral jumps and CMJ. Bilateral 160% jump RFD
      was significantly higher than CMJ and unilateral jumps but significantly lower
      than the other bilateral jumps. In conclusion, the characteristics of the
      bilateral jumps were substantially different from those of the CMJ and unilateral
      hurdle jumps. As bilateral hurdle jumps with a height between 100 and 140% of the
      CMJ provide similar CTs and VGRF as many reported sprint or jump actions, they
      may be considered a more training-specific power training drill than the CMJ.

PMID- 21873904
TI  - Upper-body anthropometric and strength measures and their relationship to start
      time in elite luge athletes.
AB  - Start time has been shown to be a significant predictor of overall performance in
      the sport of luge. The starting motion in luge has been described as an explosive
      upper-body movement that requires significant technique and skill to perfect.
      This study aims to investigate upper-body factors that may relate to start time
      in luge. Twenty-two subjects participated in the study as part of their normal
      off-season training. Each subject had a minimum of 3 years' experience in the
      sport of luge, and at the time was a member of a U.S. Luge National Team.
      Subjects completed a 1 repetition maximum (1RM) in the bench press (BP), prone
      row (PR), and weighted pull-up (WP). Anthropometric distances were taken
      measuring finger-tip span (FS), biacromial breadth (BB), acromio-radial length,
      acromio-olecranon length (AO), hand length, and sitting cervical height. Subjects
      were divided into 2 groups based on which U.S. Luge National team they were
      currently a member of, Senior National (SN, n = 13) and Junior National (JN, n =
      9). A Pearson product-moment correlation coefficient showed several significant
      (p <= 0.05) relationships between upper-body variables and start time among the
      groups. The BP and PR 1RM were shown to have a significant relationship in both
      groups. Among the anthropometric variables, AO was also significant in both
      groups. The WP, FS, BB, and height were all shown to have a significant
      relationship with start time in the SN group, but not in the JN group. These
      results suggest that as luge athletes become more efficient in the starting
      technique, outside factors such as upper-body strength and anthropometric
      measures play a larger role in performance.

PMID- 21873906
TI  - The effect of assisted and resisted sprint training on acceleration and velocity
      in Division IA female soccer athletes.
AB  - This investigation evaluated the effects of a 4-week, 12-session training program
      using resisted sprint training (RST), assisted sprint training (AST), and
      traditional sprint training (TST) on maximal velocity and acceleration in
      National Collegiate Athletic Association (NCAA) Division IA female soccer
      athletes (n = 27). The subjects, using their respective training modality,
      completed 10 maximal effort sprints of 20 yd (18.3 m) followed by a 20-yd (18.3
      m) deceleration to jog. Repeated measures multivariate analyses of variance and
      analyses of variance demonstrated significant (p < 0.001) 3-way interactions
      (time * distance * group) and 2-way interactions (time * group), respectively,
      for both velocity and acceleration. Paired t-tests demonstrated that maximum 40
      yd (36.6-m) velocity increased significantly in both the AST (p < 0.001) and RST
      (p < 0.05) groups, with no change in the TST group. Five-yard (4.6-m), 15-yd
      (13.7 m), 5- to 15-yd (4.6- to 13.7-m) acceleration increased significantly (p <
      0.01) in the AST group and did not change in the RST and TST groups. Fifteen- to
      25-yd (13.7- to 22.9-m) acceleration increased significantly (p < 0.01) in the
      RST group, decreased significantly (p < 0.01) in the AST group, and was unchanged
      in the TST group. Twenty-five to 40-yd (22.9- to 36.6-m) acceleration increased
      significantly (p < 0.05) in the RST group and remained unchanged in the AST and
      TST groups. It is purposed that the increased 5-yd (4.6-m) and 15-yd (13.7-m)
      accelerations were the result of enhanced neuromuscular facilitation in response
      to the 12-session supramaximal training protocol. Accordingly, it is suggested
      that athletes participating in short distance acceleration events (i.e., <=15 yd;
      <=13.7 m) use AST protocols, whereas athletes participating in events that
      require greater maximum velocity (i.e., >15 yd; > 13.7 m) should use resisted
      sprint training protocols.

PMID- 21873907
TI  - Dynamic evaluation of a quadricuspid aortic valve with coronary computed
      tomography angiography.
AB  - A 35-year-old man presented with 9 years of chronic chest pain and was found to
      have moderate-to-severe aortic regurgitation on echocardiography. Aortic valve
      morphology on the initial echocardiogram was deemed normal. Computed tomography
      angiography was obtained for further evaluation of the aortic root dimension and
      anatomy. In addition to noninvasive evaluation of the coronary arteries, the
      higher spatial resolution and volumetric coverage of computed tomography
      angiography can better define the valvular and aortic anatomy. Reconstruction of
      retrospectively gated cine images through the aortic valve plane revealed a
      quadricuspid valve with 4 equal-sized cusps. Incomplete coaptation of the aortic
      valve cusps was seen during diastole, explaining the marked aortic regurgitation.
      In addition, a dilated ascending thoracic aorta (4.7 cm) was revealed. On the
      basis of these findings, the patient was treated surgically with a composite
      valve graft replacement of his aortic root.

PMID- 21873908
TI  - Image quality of computed tomographic pulmonary angiography for suspected
      pulmonary embolus in patients with diffuse interstitial lung disease.
AB  - PURPOSE: To investigate the effect of diffuse interstitial lung disease (DILD) on
      the image quality of computed tomographic pulmonary angiography (CTPA). MATERIALS
      AND METHODS: The study group comprised 130 patients with DILD who underwent CTPA
      between April 2005 and April 2009. One hundred and thirty patients without
      significant parenchymal lung disease were used as a control group. Contrast
      enhancement of pulmonary arteries in the left upper lobe and right lower lobe was
      evaluated to the sub-subsegmental level both subjectively and objectively. The
      global and lobar extents of interstitial lung disease were also estimated in the
      study group. Subjective assessment was performed by 2 observers, initially
      independently and subsequently by consensus in cases of discordance. RESULTS: At
      the sub-subsegmental level, the number of patients with adequately opacified
      arteries was significantly lower in the DILD group (29.2% left upper lobe, 36.2%
      right lower lobe) compared with the control group (78.5% left upper lobe, 89.2%
      right lower lobe) (P<0.001). Subjective image quality scores of the sub
      subsegmental arteries were strongly correlated with mean vascular attenuation
      values at this level (P<0.001) but not to the global or lobar extent of lung
      parenchymal disease. There was no clinically significant difference in image
      quality (either subjectively or objectively) between the DILD and control groups
      in the subsegmental and more proximal arterial branches. CONCLUSIONS: In the
      majority of patients with DILD, CTPA image quality is sufficient only to the
      subsegmental level. Emboli at the sub-subsegmental level, which may have greater
      clinical significance in patients with DILD than in those without, are unlikely
      to be excluded using CTPA.

PMID- 21873909
TI  - 3D-CT lung volumetry using multidetector row computed tomography: pulmonary
      function of each anatomic lobe.
AB  - PURPOSE: We sought to determine the volume of each anatomic lung lobe
      reconstructed using 3-dimensional computed tomography (3D-CT) imaging from
      multidetector CT images and to compare these with pulmonary function test
      results. MATERIALS AND METHODS: We reviewed preoperative 3D-CT images and
      spirometry results of 111 patients (86 men and 25 women) with pulmonary neoplasms
      who were considered candidates for lung resections. On a 3D-CT image, the entire
      lung was semiautomatically separated into 5 anatomic lobes: right upper lobe,
      right middle lobe, right lower lobe, left upper lobe, and left lower lobe. For
      each lobe, total lobar volume, emphysematous lobar volume with low attenuation
      values of less than -950 HU, and normal lobar volume (NLV=total lobar volume
      emphysematous lobar volume) were calculated. Vital capacity, forced expiratory
      volume in 1 second, and diffusing capacity for carbon monoxide (DLCO) were
      measured by spirometry. Relationships between NLV values of each lobe and
      pulmonary function results were determined by the Pearson correlation
      coefficients and multiple regression analysis. RESULTS: The NLV values for both
      lower lobes (right lower lobe and left lower lobe) and the other lobes (right
      upper lobe, right middle lobe, and left upper lobe) were significantly correlated
      with vital capacity and forced expiratory volume in 1 second; lower lobes showed
      a stronger tendency toward these correlations. The NLV values of the lower lobes
      were significantly correlated with DLCO (P<0.001), although the NLV values of the
      other lobes were not correlated with DLCO (P=0.112). CONCLUSIONS: Pulmonary
      function results, particularly DLCO, were primarily affected by the NLVs of the
      lower lobes.

PMID- 21873910
TI  - Incontinence brief use in acute hospitalized patients with no prior incontinence.
AB  - PURPOSE: The aim of the study was to evaluate the incidence of in-hospital
      incontinence brief use among older patients who did not use diapers prior to
      admission. A second aim was to identify factors affecting the use of incontinence
      briefs, commodes, urinals, and self-toileting. SUBJECTS AND SETTING: The study
      was conducted in 5 medical acute-care units of a 900-bed teaching hospital in
      Israel. The data presented here were collected from a total of 465 patients (age
      >= 70 years) who did not use incontinence briefs prior to admission. METHODS: The
      current study is part of a larger prospective cohort study conducted from
      February to November 2009. Patients or proxies were interviewed on admission
      regarding their functional status, mobility, continence status, and type of
      voiding patterns prior to hospital stay. Interviews regarding in-hospital voiding
      and mobility patterns were conducted each day after the first 48 hours of
      hospitalization. Electronic medical records were extracted to calculate the
      severity of illness, comorbidity score, and length of hospital stay. RESULTS: The
      incidence of in-hospital adult incontinence brief use was 14% (65/465), whereas
      the rate of in-hospital commodes/urinals was 8.2% (38/465). The relative risk
      (RR) of incontinence brief use versus self-toileting was 18.76 (95% confidence
      intervals [CI]: 4.36-43.72) and 10.12 (95% CI: 2.23-13.48) higher for patients
      with low or moderate in-hospital mobility, respectively, versus those who were
      highly mobile. Patients who used incontinence briefs were more likely to be
      female (RR = 1.65; CI: 1.20-2.23) and were more likely to have low mobility (RR =
      1.59; 95% CI: 1.10-2.35) than patients who used commodes/urinals. CONCLUSIONS:
      Adult incontinence briefs are frequently used in continent patients, especially
      women, with low mobility. However, the current literature identifies incontinence
      briefs use as leading to multiple adverse outcomes. Therefore, the use of adult
      incontinence briefs among hospitalized older adults requires more scrutiny.

PMID- 21873911
TI  - The meanings of silence in Brazilian women with urinary incontinence.
AB  - PURPOSE: We explored the meanings of silence for Brazilian women with urinary
      incontinence (UI). SUBJECTS AND SETTING: The sample consisted of 8 women, aged 30
      to 45 years. Respondents worked as housekeepers or cleaning staff and were from
      lower social, economic, and educational strata. Their years of formal education
      varied from 0 to 8 years and they earned up to 4.5 times the Brazilian minimum
      wage, which is equivalent to US$900. METHODS: A qualitative method using
      semistructured interviews was employed to gather data. Individual semistructured
      interviews were recorded and subsequently transcribed, including researchers'
      observations of subjects' nonverbal behaviors. The interviews began with the
      question: "Can you tell me about your experience with urinary incontinence?" Data
      were analyzed using a content analysis technique. RESULTS: Respondents avoided
      discussing UI and initially resisted labeling themselves as incontinent, but
      their nonverbal behaviors provided clues to the psychosocial distress caused by
      urinary leakage. Results suggest that respondents' underprivileged social,
      economic, and cultural situation may aggravate their limitations when expressing
      their feelings. We found that the women employed silence as a means to contain
      the psychosocial distress created by their UI, and that the silence itself should
      be interpreted as an expression of distress associated with UI. CONCLUSION: The
      silence of Brazilian women with UI is an essential element of communication about
      incontinence. We believe that the silence used by these women expresses the pain
      and anxiety they experienced, and it acts as an adaptive psychosocial mechanism.

PMID- 21873912
TI  - Retention cuff pressure study of 3 indwelling stool management systems:
      randomized study of 10 healthy subjects.
AB  - PURPOSE: The purpose of this study was to compare retention cuff pressures of 3
      indwelling stool management systems while subjects assumed different body
      positions and while cuffs were inflated to different volumes. METHODS: Retention
      cuff pressure study of 3 indwelling stool management systems was a randomized,
      crossover, open-label pilot study of 10 healthy adult volunteers in 3 body
      positions (supine, right side, and left side), 3 head-of-bed elevations (20
      degrees , 30 degrees , and 40 degrees ), and 3 cuff overfill volumes (5, 10, and
      15 mL). The devices were DigniCare Stool Management System (device A; Bard
      Medical Division, C. R. Bard, Inc, Covington, Georgia), Flexi-Seal Fecal
      Management System (device B; ConvaTec, a division of E. R. Squibb & Sons, LLC,
      Princeton, New Jersey), and ActiFlo Indwelling Bowel Catheter System (device C;
      Hollister, Inc, Libertyville, Illinois). We assessed cuff pressure by manometry
      and rectal mucosa by digital examination and small-diameter, flexible endoscopy.
      RESULTS: Cuffs were appropriately seated in the rectal vault for all 3 devices in
      all body positions and overfill volumes. Rectal mucosal abnormalities were
      observed in 4 of 10 subjects (40%) after removal of device A, 1 of 5 (20%) after
      removal of device B, and 3 of 5 (60%) after removal of device C. Retention cuff
      pressure was at least 2-fold lower for device A than for device B or C in all
      body positions, head-of-bed elevations, and device overfill volumes. For example,
      mean pressure while subjects were on their left sides was 25.0 mm Hg for device
      A, 79.2 mm Hg for device B, and 67.2 mm Hg for device C. Corresponding pressures
      at 15 mL of overfill were 52.5, 102.0, and 94.0 mm Hg. Subject comfort scores
      were comparable for all 3 devices. CONCLUSION: All devices appeared to seat well
      within the rectal vault, but device A was associated with cuff pressure
      measurements that were consistently lower than those of devices B and C. More
      studies are needed to elucidate the clinical relevance of these findings and
      whether they translate to differences in patient safety or comfort.

PMID- 21873913
TI  - MASD part 3: peristomal moisture- associated dermatitis and periwound moisture
      associated dermatitis: a consensus.
AB  - Moisture-associated skin damage (MASD) occurs when excessive moisture in urine,
      stool, and wound exudate leads to inflammation of the skin, with or without
      erosion or secondary cutaneous infection. This article, produced by a panel of
      clinical experts who met to discuss moisture as an etiologic factor in skin
      damage, focuses on peristomal moisture-associated dermatitis and periwound
      moisture-associated dermatitis. The principles outlined here address assessment,
      prevention, and treatment of MASD affecting the peristomal or periwound skin.

PMID- 21873914
TI  - Fibromyalgia symptoms, physical function, and comorbidity in middle-aged and
      older adults.
AB  - BACKGROUND: Multiple studies report on symptoms or physical function in people
      with fibromyalgia; however, limited studies have been focused on older adults
      with fibromyalgia. OBJECTIVES: The aims of this study were to describe the
      occurrence, frequency, severity, and distress of symptoms and to examine
      differences in symptoms and physical function between a middle-aged and an older
      group. METHOD: Questionnaires were mailed to a random sample of 533 adults with
      fibromyalgia over 50 years of age, using a large tertiary care database. These
      questionnaires included an investigator-developed 29-item symptom questionnaire
      that measured the frequency (1-4), severity (1-4), and distress (0-4) of FM
      symptoms. The participants also completed the Late Life Function and Disability
      Instrument and the Charlson Comorbidity Index. RESULTS: Fifty-three percent of
      the sample reported at least 20 symptoms in the last 7 days. The most frequent
      and severe symptoms were pain, nonrefreshing sleep, fatigue, stiffness,
      difficulty staying asleep, difficulty falling asleep, and profuse sweating. The
      most distressing symptoms were fear of symptoms worsening, followed by difficulty
      staying asleep, fatigue, nonrefreshing sleep, and restless legs. Participants
      reported moderate functional limitations (M +/- SD = 52.7 +/- 9.0). Comorbidities
      were low (1.7 +/- 1.5; range = 0-7). The middle-aged group experienced a greater
      number of total symptoms (21.4 +/- 5.9 vs. 19.3 +/- 5.2; p < .01). DISCUSSION:
      Middle-aged adults with fibromyalgia were more symptomatic than older adults.
      Further study is needed to understand the relationship between fibromyalgia
      symptoms and age and physical function.

PMID- 21873915
TI  - Validity of self-rated hearing compared with audiometric measurement among
      construction workers.
AB  - BACKGROUND: A valid assessment of hearing status is important to detect hearing
      loss early and prevent further loss in noise-exposed individuals or older adults.
      Self-report is used widely in research and is often the only possible measure to
      evaluate hearing ability. OBJECTIVES: The aims of this study were to establish
      the level of validity of self-rated hearing by comparing it with the results of
      audiograms and to examine correlations and changes in self-rated and measured
      hearing status over time. METHODS: Survey and audiogram data collected from 403
      construction workers at two different time points (Years 1 and 2) were used in
      the hearing protection intervention study. Self-rated hearing was assessed on a 5
      point rating scale using a single question ("How do you rate your hearing?").
      Hearing was measured via audiograms conducted at frequencies 0.5 through 8 kHz.
      Three pure-tone threshold average (PTA) indicators, PTA 0.5-2 kHz, PTA 0.5-3 kHz,
      and PTA 4-6 kHz, of the worse ear were used and compared with self-ratings at two
      time points. RESULTS: Percentage of agreement between the self-rated and measured
      hearing was lowest in PTA 4-6 kHz and highest in PTA 0.5-3 kHz for both years.
      Cohen's kappas showed fair to moderate (.25-.45) agreement. Sensitivity was
      higher (.82-.89) in the speech frequencies and lower (.51-.55) at higher
      frequencies. Specificity was better at higher frequencies than at lower
      frequencies (.83-.89 vs .68-.74). Although there was no appreciable change in
      self-rated hearing and limited change in measured hearing on all 3 indicators
      from Years 1 to 2, correlations between self-rated and measured hearing were
      higher in Year 2. DISCUSSION: A single-item question about an individual's
      hearing ability is moderately useful and valid to assess hearing loss and can be
      recommended for a population-based study only if audiograms are not available,
      but self-report hearing screening should not be considered an adequate substitute
      for the standardized audiometric test. Providing audiograms and feedback on the
      results apparently enhanced individuals' ability to judge their hearing status.

PMID- 21873916
TI  - Advances in mediation analysis can facilitate nursing research.
AB  - BACKGROUND: Two recent advances in the statistical methods for testing hypotheses
      about mediation effects are important for nursing science. First, bootstrap
      sampling distributions provide more accurate tests of hypotheses about mediated
      effects. Second, methods for testing statistical hypotheses about subgroup
      differences in mediation models (moderated mediation) are now well developed.
      OBJECTIVE: The aims of this study were to demonstrate the use and relatively
      simple computation of bootstrap sampling distributions in tests of mediation
      effects and to demonstrate a recently refined method for testing hypotheses about
      moderated mediation. METHOD: Using hypothetical data, a step-by-step
      demonstration was provided of the construction of a bootstrap sampling
      distribution for a correlation coefficient. Then, tests of mediation and
      moderated mediation were demonstrated using data from a clinical trial of an
      intervention for caregivers of patients with Parkinson's disease or Alzheimer's
      disease. In a model hypothesizing that mutuality between caregiver and care
      recipient mediates the effect of objective on subjective levels of caregiver
      burden, the bootstrap sampling distribution was calculated of the mediation
      effect and, from that, two types of 95% confidence intervals for it. Then the
      hypothesis was tested that the mediating effect of mutuality was stronger for
      caregivers of patients with Parkinson's disease than for caregivers of patients
      with Alzheimer's disease. CONCLUSIONS: Statistical hypothesis testing should
      never dictate all conclusions. However, the statistical advances in mediation
      analysis described here will facilitate nursing research as both nurse scientists
      and methodologists understand their assumptions and logic.

PMID- 21873917
TI  - Tobit model for outcome variable is limited by censoring in nursing research.
AB  - BACKGROUND: In nursing research, censoring may limit the outcome variable of
      interest. Well-known examples reflect the so-called floor or ceiling effect.
      Offering a biased estimator of the limited data, the linear regression model with
      ordinary least-squares estimation is one of the most frequently used methods.
      This method requires an innovative approach. OBJECTIVES: The aims of this study
      were to (a) introduce an alternative data analysis approach (Tobit model), (b)
      discuss the constraints of ordinary least-squares regression and complementary
      advantages of the Tobit model in working with censoring data, and (c) provide a
      fundamental understanding of the Tobit model in the nursing and healthcare
      domains. METHOD: The benefits of the Tobit model are outlined using an example of
      activities of daily living. RESULTS: Based on model-fit parameters, residual
      plots, regression coefficients, and significance levels, the results indicate
      that the Tobit model performs more accurately than an ordinary least-squares
      regression when data are subject to a ceiling or floor effect. CONCLUSION: When
      the Tobit model is specified correctly, it allows nursing researchers to
      ameliorate biased coefficient estimates occurring when health status measures are
      subject to limited data by censoring. Despite the theoretical superiority of the
      Tobit model to classical statistical data analysis, nurse researchers are
      cautioned to be aware of the limitations and appropriate applications associated
      with the Tobit model.

PMID- 21873918
TI  - Translation and validation of a chinese version of the family sense of coherence
      scale in Chinese childbearing families.
AB  - BACKGROUND: Family sense of coherence is central to successful coping with family
      stressors and facilitates positive adaptation. Little is known about the
      implications of family sense of coherence for family adaptation during the
      transition to parenthood in Chinese society. OBJECTIVES: The aims of this study
      were to translate the Family Sense of Coherence Scale-Short Form (FSOC-S) into
      Chinese FSOC-S (C-FSOC-S) and to evaluate the psychometric properties. METHODS:
      In Phase 1, the FSOC-S was translated into Chinese using the translation/back
      translation technique and was reviewed by an expert panel for cultural
      equivalence. In Phase 2, a cross-sectional survey was conducted using a
      convenience sample of 128 Chinese childbearing couples recruited from the
      antenatal clinics. Participants completed the C-FSOC-S, Sense of Coherence Scale,
      Medical Outcomes Study Family and Marital Functioning Measures, and State-Trait
      Anxiety Inventory. RESULTS: The C-FSOC-S showed good internal consistency
      (Cronbach's alpha = .83) and test-retest reliability (intraclass correlation
      coefficient = .75). Significant correlations with Sense of Coherence Scale (r =
      .55, p < .01), Medical Outcomes Study Family and Marital Functioning Measures (r
      = .71, p < .01), and State-Trait Anxiety Inventory (r = -.50, p < .01) indicated
      good construct validity. Exploratory factor analysis revealed a single-factor
      structure of the C-FSOC-S. DISCUSSION: The C-FSOC-S has satisfactory psychometric
      properties and has the potential to be used as a clinical and research instrument
      for measuring family sense of coherence in Chinese childbearing families.

PMID- 21873919
TI  - Predictors of dietary quality in low-income pregnant women: a path analysis.
AB  - BACKGROUND: Despite the potential importance of nutrition to pregnancy outcomes,
      little is known about the factors influencing dietary quality, especially during
      the first trimester. OBJECTIVE: The aim of this study was to examine the
      relationships of distress (an index of depression and stress), social support,
      and eating habits with dietary quality in low-income pregnant women. METHOD: A
      cross-sectional design and path analytic methods was used in a clinic-based
      sample of low-income women (n = 118) in their first trimester of pregnancy. Women
      completed questionnaires and received training on estimating food portion sizes.
      Three 24-hour dietary recalls were collected over 2 weeks. Overall dietary
      quality was assessed using the Dietary Quality Index-Pregnancy. RESULTS: The
      final path model fit well (comparative fit index [CFI] = .97, root mean square
      error of approximation [RMSEA] = .05) and revealed that distress had a direct
      effect on poor eating habits (beta = .36) and a direct (beta = -.23) and indirect
      effect on dietary quality (beta = -.30). Poor eating habits had a direct effect
      on dietary quality (beta = -.18). Social support had no effect on dietary
      quality. Age had significant direct effects on education (beta = .39) and
      nutritional knowledge (beta = .18) and an indirect effect on dietary quality
      (total effect, beta = .19). Maternal age, education, and nutritional knowledge
      did not have significant effects on psychosocial variables. DISCUSSION:
      Psychosocial distress and poor eating habits contributed to inadequate dietary
      quality. Assessing for depression, stress, poor eating habits, and overall
      dietary quality during the crucial first trimester may identify women needing
      more intensive dietary monitoring and intervention throughout pregnancy.

PMID- 21873920
TI  - Passive sensor technology interface to assess elder activity in independent
      living.
AB  - BACKGROUND: The effectiveness of clinical information systems to improve nursing
      and patient outcomes depends on human factors, including system usability,
      organizational workflow, and user satisfaction. OBJECTIVE: The aim of this study
      was to examine to what extent residents, family members, and clinicians find a
      sensor data interface used to monitor elder activity levels usable and useful in
      an independent living setting. METHODS: Three independent expert reviewers
      conducted an initial heuristic evaluation. Subsequently, 20 end users (5
      residents, 5 family members, 5 registered nurses, and 5 physicians) participated
      in the evaluation. During the evaluation, each participant was asked to complete
      three scenarios taken from three residents. Morae recorder software was used to
      capture data during the user interactions. RESULTS: The heuristic evaluation
      resulted in 26 recommendations for interface improvement; these were classified
      under the headings content, aesthetic appeal, navigation, and architecture, which
      were derived from heuristic results. Total time for elderly residents to complete
      scenarios was much greater than for other users. Family members spent more time
      than clinicians but less time than residents did to complete scenarios. Elder
      residents and family members had difficulty interpreting clinical data and
      graphs, experienced information overload, and did not understand terminology. All
      users found the sensor data interface useful for identifying changing resident
      activities. DISCUSSION: Older adult users have special needs that should be
      addressed when designing clinical interfaces for them, especially information as
      important as health information. Evaluating human factors during user
      interactions with clinical information systems should be a requirement before
      implementation.

PMID- 21873921
TI  - Changing the sheets: a new system to reduce strain during patient repositioning.
AB  - BACKGROUND: Manually repositioning patients puts healthcare providers at risk for
      injury; this may be reduced by using low-friction bedsheets. OBJECTIVES: The aim
      of this study was to evaluate the physical properties and the physiological
      measures of muscle activity and perceptual participant accounts between a new
      slider sheet system and traditional hospital bedsheet makeup (soaker pad with a
      jersey bottom sheet). METHOD: Surface electromyography was recorded from the arm
      and shoulder muscles of five healthcare providers executing a patient
      repositioning (boosting and turning) in a controlled laboratory setting to gain
      an indication of muscle activity required for two types of bedsheets (slider
      system and traditional sheet makeup). The Borg Scale was used to establish rating
      of perceived exertion for these repositioning tasks on the two types of bedsheet
      makeup. To evaluate the sheets independent of human interaction and contact, the
      physical resistive characteristics of the sheets were calculated by determining
      the coefficient of friction. RESULTS: Patient repositioning on traditional
      sheets, compared with the slider system, resulted in 16% greater electromyography
      burst numbers and 11% longer duration for both boosting and turning. Moreover,
      ratings of perceived exertion for repositioning patients on traditional sheets
      versus on slider sheets were more than double. The coefficient of friction of the
      traditional sheets was 65% less in the slider sheet system. DISCUSSION: This
      study suggests that manually repositioning patients on a low-friction slider
      system reduces muscular and perceived effort. Proper usage of this type of
      bedsheets may reduce the risks associated with musculoskeletal strain and
      injuries of the healthcare providers.

PMID- 21873923
TI  - Inferior field loss increases rate of falls in older adults with glaucoma.
AB  - PURPOSE: To examine the visual predictors of falls and injurious falls among
      older adults with glaucoma. METHODS: Prospective falls data were collected for 71
      community-dwelling adults with primary open-angle glaucoma (mean age, 73.9 +/-
      5.7 years) for 1 year using monthly falls diaries. Baseline assessment of central
      visual function included high-contrast visual acuity and Pelli-Robson contrast
      sensitivity. Binocular integrated visual fields were derived from monocular
      Humphrey Field Analyzer plots. Rate ratios (RR) for falls and injurious falls
      with 95% confidence intervals (CIs) were based on negative binomial regression
      models. RESULTS: During the 1-year follow-up, 31 (44%) participants experienced
      at least one fall and 22 (31%) experienced falls that resulted in an injury.
      Greater visual impairment was associated with increased falls rate, independent
      of age and gender. In a multivariate model, more extensive field loss in the
      inferior region was associated with higher rate of falls (RR, 1.57; 95% CI, 1.06
      to 2.32) and falls with injury (RR, 1.80; 95% CI, 1.12 to 2.98), adjusted for all
      other vision measures and potential confounding factors. Visual acuity, contrast
      sensitivity, and superior field loss were not associated with the rate of falls;
      topical beta-blocker use was also not associated with increased falls risk.
      CONCLUSIONS: Falls are common among older adults with glaucoma and occur more
      frequently in those with greater visual impairment, particularly in the inferior
      field region. This finding highlights the importance of the inferior visual field
      region in falls risk and assists in identifying older adults with glaucoma at
      risk of future falls, for whom potential interventions should be targeted.

PMID- 21873924
TI  - Ocular dominance stability and reading skill: a controversial relationship.
AB  - PURPOSE: Evidence is mixed concerning the relationship between stability of
      ocular dominance and reading deficits. Contrasting results may be due to the use
      of different tests of dominance, different samples of readers, and different
      scoring methods. The aim of this study was to investigate the relationship among
      ocular dominance, general visual abilities, and reading performance, and to
      evaluate the consistency and reliability of different tests of ocular dominance
      and the effects of different types of eye dominance scoring. METHODS: In a group
      of young adults, we measured: (a) main optometric parameters; (b) reading time
      and accuracy; and (c) ocular dominance in two sighting and four motor tests.
      Dominance was determined using different scoring methods (relative, absolute, and
      binary scores). RESULTS: All dominance tests showed good levels of internal
      reliability. Sighting tests were consistent regardless of the scoring method, and
      all participants had stable dominance. Three of four motor tests were moderately
      consistent when dominance was measured with relative scores but not when it was
      measured with absolute or binary scores. No relationship was found between
      stability of dominance and reading performance, regardless of the type of test or
      scoring method. No systematic pattern of correlation was found between binocular
      vision variables and dominance measures. CONCLUSIONS: Choosing the type of motor
      test to measure ocular dominance is crucial, because the level of consistency
      among tests is low to moderate. Furthermore, motor tests were not correlated with
      reading performances. Present results suggest caution when trying to link reading
      difficulties with specific profiles of ocular dominance.

PMID- 21873922
TI  - Treatment of accommodative dysfunction in children: results from a randomized
      clinical trial.
AB  - PURPOSE: To report the effectiveness of various forms of vision
      therapy/orthoptics in improving accommodative amplitude and facility in children
      with symptomatic convergence insufficiency (CI) and co-existing accommodative
      dysfunction. METHODS: In a randomized clinical trial, 221 children aged 9 to 17
      years with symptomatic CI were assigned to one of four treatments. Of the
      enrolled children, 164 (74%) had accommodative dysfunction; 63 (29%) had a
      decreased amplitude of accommodation with respect to age, 43 (19%) had decreased
      accommodative facility, and 58 (26%) had both. Analysis of variance models were
      used to compare mean accommodative amplitude and accommodative facility for each
      treatment group after 4, 8, and 12 weeks of treatment. RESULTS: After 12 weeks of
      treatment, the increases in amplitude of accommodation [office-based
      vergence/accommodative therapy with home reinforcement group (OBVAT) 9.9 D, home
      based computer vergence/accommodative therapy group (HBCVAT+) 6.7 D, and home
      based pencil push-up therapy group (HBPP) 5.8 D] were significantly greater than
      in the office-based placebo therapy (OBPT) group (2.2 D) (p-values <=0.010).
      Significant increases in accommodative facility were found in all groups (OBVAT:
      9 cpm, HBCVAT+: 7 cpm, HBPP: 5 cpm, OBPT: 5.5 cpm); only the improvement in the
      OBVAT group was significantly greater than that found in the OBPT group (p =
      0.016). One year after completion of therapy, reoccurrence of decreased
      accommodative amplitude was present in only 12.5% and accommodative facility in
      only 11%. CONCLUSIONS: Vision therapy/orthoptics is effective in improving
      accommodative amplitude and accommodative facility in school-aged children with
      symptomatic CI and accommodative dysfunction.

PMID- 21873925
TI  - Peripheral aberrations and image quality for contact lens correction.
AB  - PURPOSE: Contact lenses (CLs) reduced the degree of hyperopic field curvature
      present in myopic eyes and rigid CLs reduced spherocylindrical image blur on the
      peripheral retina, but their effect on higher order aberrations and overall
      optical quality of the eye in the peripheral visual field is still unknown. The
      purpose of our study was to evaluate peripheral wavefront aberrations and image
      quality across the visual field before and after CL correction. METHODS: A
      commercial Hartmann-Shack aberrometer was used to measure ocular wavefront errors
      in 5 degrees  steps out to 30 degrees  of eccentricity along the horizontal
      meridian in uncorrected eyes and when the same eyes are corrected with soft or
      rigid CLs. Wavefront aberrations and image quality were determined for the full
      elliptical pupil encountered in off-axis measurements. RESULTS: Ocular higher
      order aberrations (HOA) increase away from fovea in the uncorrected eye. Third
      order aberrations are larger and increase faster with eccentricity compared with
      the other HOA. CLs increase all HOA except third-order Zernike terms.
      Nevertheless, a net increase in image quality across the horizontal visual field
      for objects located at the foveal far point is achieved with rigid lenses,
      whereas soft CLs reduce image quality. CONCLUSIONS: Second-order aberrations
      limit image quality more than HOA in the periphery. Although second-order
      aberrations are reduced by CLs, the resulting gain in image quality is partially
      offset by increased amounts of HOA. To fully realize the benefits of correcting
      HOA in the peripheral field requires improved correction of second-order
      aberrations as well.

PMID- 21873926
TI  - Straylight and contrast sensitivity after corneal refractive therapy.
AB  - PURPOSE: To compare intraocular straylight and contrast sensitivity determined
      before corneal refractive therapy and after 15 days and 1 month of treatment.
      METHODS: A single-center, prospective, and longitudinal study was performed in 30
      subjects undergoing corneal refractive therapy. In each subject, high-contrast
      visual acuity (HCVA), low-contrast visual acuity (LCVA), straylight, and contrast
      sensitivity were determined at baseline and after 15 days and 1 month after the
      treatment. Straylight was measured using the van den Berg straylight meter (third
      generation). Contrast sensitivity was determined under both photopic and mesopic
      conditions using the VCTS 6500 instrument (Vision Contrast Test System). EDTRS
      charts (logMAR units) were used to measure HCVA and LCVA. RESULTS: Straylight
      (mean +/- standard deviation) significantly fell from baseline (0.94 +/- 0.14) to
      the values recorded at 1 month (0.85 +/- 0.11, p = 0.009). Photopic contrast
      sensitivity remained stable yet mesopic contrast sensitivity measured at high
      spatial frequencies was significantly reduced. No correlations between
      intraocular straylight and contrast sensitivity, HCVA, or LCVA were observed 15
      days and 1 month after corneal refractive therapy. CONCLUSIONS: Our findings
      suggest improved intraocular straylight readings 1 month after starting the
      treatment, although the changes observed in straylight could not be related to
      changes in mesopic and photopic contrast sensitivity or HCVA and LCVA. Mesopic
      contrast sensitivity was more affected by the treatment intervention than
      photopic contrast sensitivity.

PMID- 21873927
TI  - Retinal angiomatosis and cystoid macular oedema in Cogan's syndrome.
AB  - PURPOSE: To describe clinical features and visual and therapeutic outcomes in a
      patient affected by Cogan's syndrome with retinal angiomatosis and cystoid
      macular edema (CMO). CASE REPORT: A 46-year-old Caucasian man reported frequent
      episodes of eye redness and pain, conjunctivitis, xerophthalmia, photophobia, and
      progressive worsening of visual acuity. Slitlamp examination revealed
      interstitial keratitis. Pan-fundus fluorescein and indocyanine green
      angiographies revealed the presence of CMO, optic disc edema, and a peripheral
      angiomatous-like lesion in OS. The audiogram revealed bilateral sensorineural
      deafness. Blood cultures and genetic counseling and tumor screening tests were
      negative; antibodies against both CD148/DEP1 and Cogan peptide were positive.
      Intravitreal injection of bevacizumab did not induce either CMO reduction or
      improvements in visual acuity. Oral administration of corticosteroids reduced CMO
      and improved visual acuity and hearing, whereas the peripheral angiomatosis still
      showed leakage. Cryotherapy of the lesion was successfully carried out to avoid
      consequent exudative retinal detachment. A close follow-up was scheduled to rule
      out a possible recurrence of CMO and/or angiomatosis. CONCLUSIONS: This case
      described Cogan's syndrome with peripheral retinal angiomatosis and CMO. It
      highlights the variability of manifestations of this rare syndrome. Delay in
      diagnosis is common and can lead to visual and auditory disability.
      Corticosteroids are the first line of treatment and early administration may aid
      recovery. Early diagnosis and treatment of peripheral retinal angiomatosis lead
      to positive visual outcomes.

PMID- 21873928
TI  - Risk factors and outcomes of Staphylococcus aureus infections after small bowel
      and multivisceral transplantation.
AB  - BACKGROUND: No studies have evaluated the risk factors and outcomes of
      Staphylococcus aureus (SA) infections in small bowel (SBT) and multivisceral
      (including small bowel) transplantation (MVT). METHODS: SBT and MVT recipients
      with SA infections (22 cases) were retrospectively identified and compared with
      matched non-SA-infected recipient controls (44). The characteristics were
      compared with Friedman and Cochran-Mantel-Haenszel tests. Conditional logistic
      regression analysis was performed to identify risk factors, and Kaplan-Meier
      curve and Cox proportional hazard model were performed for survival analysis.
      RESULTS: The median age was 2.07 years (range, 0.76-54.04). Forty-three percent
      of the first SA infections were bloodstream infections, 30% lung infections, and
      26% surgical site infections; 36% of these isolates were methicillin-resistant
      SA. Median time (days) to surgical site infections (41.0; range, 0-89) was
      significantly shorter than that to lung infections (266; range, 130-378) (P =
      0.01). By univariate analysis, it was found that cases were more likely to have
      cytomegalovirus (CMV) sero-mismatch (odds ratio [OR] = 3.03 [95% confidence
      interval, 0.88-10.43]; P = 0.08), and controls were more likely to receive
      mycophenolate mofetil (MMF) treatment (0.09 [0.001-0.82]; P = 0.03). By
      multivariable analysis, patients with CMV sero-mismatch were found to have higher
      odds of developing SA infection (OR, 2.92; P = 0.085), whereas MMF had a
      protective effect (OR, 0.08; P = 0.031), adjusting for matched criteria. SA cases
      had shorter survival than controls (mean survival, 28.5 vs. 45.8 months [P =
      0.04]) and were 2.18 times more likely to die (1.02-4.67, P = 0.04). CONCLUSIONS:
      SA infections were associated with a significant shorter survival time and higher
      risk of death. The presence of CMV sero-mismatch and the absence of MMF treatment
      were found to be the risk factors for SA infections after SBT and MVT.

PMID- 21873929
TI  - Successful treatment of Aspergillus flavus spondylodiscitis with epidural abscess
      in a patient with chronic granulomatous disease.
AB  - Chronic granulomatous disease is a genetic disorder characterized by defects in
      the ability of the phagocytes to kill ingested microbes, leading to recurrent
      bacterial and fungal infections. Vertebral osteomyelitis complicated by an
      epidural abscess from aspergillosis is rare. We report a case of Aspergillus
      spondylodiscitis with an epidural abscess in a 17-year-old autosomal recessive
      chronic granulomatous disease patient.

PMID- 21873930
TI  - Increased coronary blood flow and cardiac contractile efficiency with intraaortic
      balloon counterpulsation in a porcine model of myocardial ischemia-reperfusion
      injury.
AB  - The evaluation of the impact of intraaortic balloon pump (IABP) on postischemic
      coronary perfusion and myocardial contractile impairment has been so far limited
      to early reperfusion phase. Therefore, we analyzed the 24-hour effects of IABP on
      coronary blood flow (CBF) and left ventricular performance in an animal model of
      acute myocardial ischemia-reperfusion injury. Healthy swine (n = 20) underwent
      120-minute ligation of the left anterior descending coronary artery followed by
      24 hours of reperfusion. We randomly assigned the animals to have IABP placed in
      the descending aorta 5 minutes after reperfusion onset (n = 10) or to undergo no
      implantation (n = 10). We measured CBF, coronary resistance, cardiac cycle
      efficiency (CCE), and maximal pressure/time ratio before ischemia was induced and
      at 30 minutes and 1, 6, 12, and 24 hours after reperfusion began. During
      diastole, CBF was significantly increased in IABP compared with baseline and
      controls at all time points (all p < 0.001). This was also true during systole in
      IABP only for the first hour after reperfusion began. Additionally, both CCE and
      pressure/time ratio were significantly increased in IABP compared with baseline
      at 30 minutes and 1 hour after reperfusion began (p < 0.001). IABP was associated
      with enhanced CBF and cardiac efficiency in a model of acute ischemic-reperfusion
      injury.

PMID- 21873931
TI  - Challenges during repeat extracorporeal life support in a patient with pulmonary
      alveolar proteinosis.
AB  - Extracorporeal life support (ECLS) is used to support patients with pulmonary
      alveolar proteinosis (PAP) both during acute illness and during lung lavage
      therapies. We report the challenges encountered while providing ECLS for
      respiratory failure to a 12-year-old girl with PAP who had previously received
      ECLS as a toddler for a prior episode of respiratory failure due to PAP. She was
      placed on venovenous-arterial (VVA) ECLS and subsequently switched to venovenous
      (VV) ECLS with drainage from the right femoral vein and reinfusion by a long
      cannula placed into the right atrium. Our case illustrates standard cannulation
      may not be possible for children requiring a second ECLS course and the
      importance of considering alternative modes of cannulation and ECLS support when
      conventional methods are not possible.

PMID- 21873932
TI  - Atherosclerosis, hormone therapy, and outcomes in younger postmenopausal women:
      waiting for more answers.

PMID- 21873933
TI  - Innovation, the upper extremity surgeon's mantra?

PMID- 21873934
TI  - Interaction of alpha-melanocortin and its pentapeptide antisense LVKAT: effects
      on hepatoprotection in male CBA mice.
AB  - The genetic code defines nucleotide patterns that code for individual amino acids
      and their complementary, i.e., antisense, pairs. Peptides specified by the
      complementary mRNAs often bind to each other with a higher specificity and
      efficacy. Applications of this genetic code property in biomedicine are related
      to the modulation of peptide and hormone biological function, selective
      immunomodulation, modeling of continuous and linear epitopes, modeling of
      mimotopes, paratopes and antibody mimetics, peptide vaccine development,
      peptidomimetic and drug design. We have investigated sense-antisense peptide
      interactions and related modulation of the peptide function by modulating the
      effects of a-MSH on hepatoprotection with its antisense peptide LVKAT. First,
      transcription of complementary mRNA sequence of a-MSH in 3'->5' direction was
      used to design antisense peptide to the central motif that serves as a-MSH
      pharmacophore for melanocortin receptors. Second, tryptophan spectrofluorometric
      titration was applied to evaluate the binding of a-MSH and its central
      pharmacophore motif to the antisense peptide, and it was concluded that this
      procedure represents a simple and efficient method to evaluate sense-antisense
      peptide interaction in vitro. Third, we showed that antisense peptide LVKAT
      abolished potent hepatoprotective effects of a-MSH in vivo.

PMID- 21873935
TI  - Natural antioxidant dihydroxybenzyl alcohol blocks ritonavir-induced endothelial
      dysfunction in porcine pulmonary arteries and human endothelial cells.
AB  - BACKGROUND: Patients with HIV have an increased incidence of pulmonary artery
      hypertension. This study was designed to determine if the naturally occurring
      antioxidant dihydroxybenzyl alcohol (DHBA) could counteract the deleterious
      effects of ritonavir (RTV), an HIV-protease inhibitor known to impair endothelial
      function and increase oxidative stress. MATERIAL/METHODS: Antioxidant assays were
      performed on DHBA in a cell free system. Glutathione (GSH) levels were measured
      in human pulmonary artery endothelial cells (HPAEC) to determine the effect of
      DHBA on the level of oxidative stress in cells treated with RTV. Myograph
      analysis was performed on porcine pulmonary artery (PA) rings after treatment
      with RTV and/or DHBA. Likewise, reactive oxygen species (ROS) production was
      assessed in porcine PA rings after RTV +/- DHBA using a lucigenin reaction.
      Immunohistochemical staining for endothelial nitric oxide synthase (eNOS) was
      also performed in porcine PAs treated as above. RESULTS: DHBA demonstrated
      significant antioxidant activity in a cell free system that surpassed that of
      vitamin C. Also, treatment with DHBA reduced RTV-induced reduction in endothelium
      dependent vasorelaxation and eNOS staining and increased superoxide anion levels.
      Meanwhile, there was a reversal in RTV-induced oxidative stress leading to
      reduced GSH levels in HPAECs after treatment with DHBA. CONCLUSIONS: These
      findings suggest that the naturally occurring antioxidant DHBA reduces the
      impairment of vasomotor functions caused by RTV in porcine PAs and reduces
      oxidative stress caused by RTV in HPAEC and porcine PA rings. This study
      indicates that DHBA may have clinical applications in the prevention or treatment
      of antiretroviral drugs-associated vascular complications in patients with HIV.

PMID- 21873936
TI  - Actin cytoskeleton modulates ADMA-induced NF-kappaB nuclear translocation and
      ICAM-1 expression in endothelial cells.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide
      synthase (NOS) inhibitor, increases the activity of NF-kappaB (NF-kappaB) and
      then induces the expression of intercellular adhesion molecule-1 (ICAM-1).
      However, the mechanisms regulating ADMA-induced NF-kappaB activation are unknown.
      This study investigated the function of actin cytoskeleton for ADMA-induced NF
      kappaB activation and ICAM-1 expression in endothelial cells. MATERIAL/METHODS:
      Human umbilical vein endothelial cells (HUVEC) were cultured and left untreated
      or challenged for 24 h with 100 uM ADMA in the absence and presence of 5 uM
      cytochalasin D (Cyt D), or 1 uM Jasplakinolide (Jas). The form of actin
      cytoskeleton, the translocation of NF-kappaB, NF-kappaB DNA binding activity, and
      the expression of ICAM-1 were determined. RESULTS: ADMA increased the formation
      of stress fiber in endothelial cells, and Cyt D clearly induced destabilization
      of the actin filaments. Either stabilizing or destabilizing the actin
      cytoskeleton prevented ADMA-induced NF-kappaB activation. It also showed that the
      inhibition of NF-kappaB activity was due to the impaired NF-kappaB nuclear
      translocation. Further, stabilizing or destabilizing the actin cytoskeleton
      inhibited the expression of the NF-kappaB target protein, ICAM-1. CONCLUSIONS:
      Actin cytoskeleton may be engaged in modulated ADMA-induced NF-kappaB activation
      and thereby ICAM-1 expression in endothelial cells.

PMID- 21873937
TI  - Expression of angiotensinogen during hepatic fibrogenesis and its effect on
      hepatic stellate cells.
AB  - BACKGROUND: The liver renin-angiotensin system (RAS) plays an important role in
      promoting the development of hepatic fibrogenesis. Angiotensinogen (AGT) is an
      important precursor in tissue RAS. This study aimed to investigate the expression
      and cellular source of AGT in hepatic fibrogenesis and its effect on
      proliferation and collagen metabolism of hepatic stellate cells.
      MATERIAL/METHODS: In a rat carbon tetrachloride (CCl4)-induced liver fibrosis
      model the mRNA expression of AGT was determined by real-time PCR and the cellular
      source of AGT was determined by immunohistochemical staining. In vitro HSC-T6
      cells were transfected with AGT, and the expression plasmid, AGT shRNA plasmid
      and negative shRNA plasmid were constructed. Real-time PCR and ELISA were applied
      to determine the mRNA expressions and contents of TIMP-1, TGF-beta1, type I
      collagen and type III collagen of the cells or in the supernatants. RESULTS:
      Compared to normal liver, the AGT and alpha-SMA mRNA expressions increased at the
      early stage of hepatic fibrosis and decreased in hepatic cirrhosis. The
      expressions of AGT and alpha-SMA mRNA were correlated with the hepatic fibrosis
      (r=0.915, P=0.03). Immunohistochemistry demonstrated the activated HSCs were the
      main source of AGT due to colocalization of AGT and alpha-SMA expressions. The
      mRNA and protein of TGF-beta1, TIMP-1, type I collagen and type III collagen were
      markedly up-regulated. CONCLUSIONS: ACEI and angiotensin II type 1 receptor
      antagonist (AT1RA) could attenuate the progression of hepatic fibrosis in the
      early stage. Direct inhibition of AGT from aHSCs may become an effective
      antifibrotic anti-liver fibrosis strategy.

PMID- 21873938
TI  - Eph-A2 and Eph-A4 expression in human benign and malignant thyroid lesions: an
      immunohistochemical study.
AB  - BACKGROUND: Ephrin receptors (Ephs) are frequently overexpressed in a wide
      variety of human malignant tumors, being associated with tumor growth, invasion,
      metastasis and angiogenesis. The aim of the present study was to evaluate the
      clinical significance of Eph-A2 and Eph-A4 expression in human benign and
      malignant thyroid lesions. MATERIAL/METHODS: Eph-A2 and Eph-A4 protein expression
      was assessed immunohistochemically on paraffin-embedded thyroid tissues from 131
      patients with benign and malignant lesions. RESULTS: Eph-A2 was significantly
      overexpressed in malignant compared to benign thyroid lesions (p<0.001).
      Papillary carcinoma cases presented significantly increased Eph-A2 expression
      compared to those with hyperplasia nodules (p<0.001). Eph-A4 expression was not
      differentiated between cases with malignant or benign thyroid lesions. Papillary
      carcinoma cases presented significantly increased Eph-A4 expression compared to
      those with hyperplasia nodules (p=0.006). In the subgroup of malignant thyroid
      lesions, Eph-A2 and Eph-A4 expression was not associated with TNM stage,
      capsular, lymphatic or vascular invasion. CONCLUSIONS: The present data suggest
      that Eph-A2, but not Eph-A4, overexpression may be associated with the malignant
      transformation of thyroid neoplasia. Further studies conducted on cohorts
      including a higher proportion of patients with advanced nodal and metastatic
      disease are recommended to draw definite conclusions on the clinical significance
      of Eph proteins in thyroid neoplasia.

PMID- 21873939
TI  - Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells--an
      ultrastructural and immunohistochemical study.
AB  - BACKGROUND: Androgen abuse is an increasing problem amongst professional and
      amateur athletes. Moreover, testosterone, apart from its widely accepted
      indications, is used for a variety of other indications such as aging and
      ischemia. Its actions are mainly attributed to a specific genomic mechanism
      through the androgen receptor, but emerging evidence reveals non-genomic effects
      as well. The use of androgens has been linked with several adverse effects. The
      purpose of this study was to examine the effects of testosterone on the
      morphology and the ultrastructure of the myocardium and to investigate the
      possible role of apoptosis. MATERIAL/METHODS: We used 12 adult male Wistar rats,
      separated into 2 groups. Group A consisted of 6 rats that were administered high
      doses of testosterone enanthate, while group B consisted of 6 male Wistar rats
      that received placebo (normal saline) intramuscularly. After the last day of
      treatment, all rats were anesthetized and sacrificed, and the hearts were removed
      and processed for optical and electron microscopy and immunohistochemical
      detection of caspase-3, an apoptosis marker. RESULTS: We found significant
      myocardial hypertrophy along with abundant ultrastructural alterations. The
      immunohistochemical staining of the myocardial cells for caspase-3 was positive
      in group A (experimental group), which is interpreted as an activation of
      apoptosis by testosterone treatment. CONCLUSIONS: Testosterone abuse has serious
      adverse effects, including myocardial hypertrophy, myocardial fibrosis and
      activation of apoptosis. These findings need to be taken into account whenever
      androgens are prescribed to improve performance or as hormone therapy.

PMID- 21873940
TI  - A severe complication after ST-segment elevation myocardial infarction (Part 1).
AB  - We report the case of a 70-year-old woman with ST-segment elevation myocardial
      infarction of the anterior wall, complicated by ventricular septal rupture (two
      septal defects--VSDs) with symptoms of cardiogenic shock. After 6 weeks of
      conservative treatment with inotropes and intra-aortic balloon support, the
      patient underwent surgical repair of VSDs with good clinical outcome.

PMID- 21873941
TI  - Association of clinical and aetiologic subtype of acute ischaemic stroke with
      inflammation, oxidative stress and vascular function: a cross-sectional
      observational study.
AB  - BACKGROUND: The role of inflammation, vascular dysfunction and oxidative stress
      in the pathophysiology of different stroke subtypes is not well understood. We
      aimed to determine if the clinical and aetiologic subtype of acute ischaemic
      stroke influences systemic markers of vascular function, inflammation and
      oxidative stress. MATERIAL/METHODS: 129 men and women were recruited within 10
      days of acute ischaemic stroke or TIA at two tertiary hospitals in this cross
      sectional observational study. Stroke severity (NIHSS score and S100B
      concentration); systemic markers of inflammation (high sensitivity C-reactive
      protein [hs-CRP] and fibrinogen), endothelial activation (E-selectin),
      endothelial cell damage (von Willebrand factor activity), and oxidative stress
      (F2-isoprostanes) were measured. RESULTS: Hs-CRP concentrations were higher in
      total anterior (22.0 +/- 24.1 mg/L) than partial anterior circulation (15.3 +/-
      32.4 mg/L) and lacunar (4.9 +/- 4.3 mg/L) syndromes (p = 0.01). Hs-CRP
      concentrations correlated moderately with NIHSS score (r = 0.45, p < 0.01) and
      S100B (r = 0.48, p < 0.01). However aetiologic and clinical subtypes were not
      independently associated with hs-CRP when included with stroke severity in
      general linear models. CONCLUSIONS: These data suggest that stroke aetiology and
      clinical syndrome may not be important independent determinants of the degree of
      systemic inflammation, oxidative stress or endothelial function in acute
      ischaemic stroke. Other factors, including stroke severity, pre-morbid
      inflammation and co-morbidity may explain variations among groups of participants
      with different subtypes of acute ischaemic stroke.

PMID- 21873942
TI  - Altered serum creatine kinase level and cardiac function in ischemia-reperfusion
      injury during percutaneous coronary intervention.
AB  - BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) resulting from primary
      percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is
      considered harmful to the patient, but its clinical significance remains unclear.
      This study explored the relationship of cardiac function examined by
      echocardiography and serum creatine kinase (CK) and CK-MB levels with MIRI in a
      cohort of Chinese AMI patients. MATERIAL/METHODS: We retrospectively analysed the
      clinical and angiographic data in 228 AMI patients in whom the infarct-related
      artery (IRA) was successfully recanalized by primary PCI. Cardiac function was
      evaluated by use of echocardiography before discharge from hospital. RESULTS: The
      in-hospital mortality rate in the MIRI group was 13.4% (16/119), which was
      significantly higher than the 4.6% (5/109) mortality rate in the non-MIRI group
      (P=0.021). The median of peak serum CK level was remarkably lower in the
      suppression-type MIRI group than in the non-MIRI group. There were no significant
      differences in the peak serum CK or CK-MB levels between the irritation-type MIRI
      group and the non-MIRI group. The peak CK and CK-MB levels were significantly
      higher in the no-reflow-type MIRI group than in the non-MIRI group. Left
      ventricular ejection fraction in the no-reflow-type MIRI group was significantly
      lower than in the non-MIRI group; left ventricular end-diastolic volume was
      significantly higher than in the irritation-type MIRI subgroup; and left
      ventricular end-systolic volume was greater than that in non-MIRI group and
      suppression-type MIRI group. CONCLUSIONS: MIRI (especially the no-reflow type)
      may lead to acute hemodynamic disorders and increase the mortality rate. However,
      suppression- and irritation-type MIRI may imply the existence of surviving
      myocardium.

PMID- 21873943
TI  - Significant oral graft-versus-host disease after allogeneic stem cell
      transplantation with the FLU/MEL conditioning regimen.
AB  - BACKGROUND: Oral graft-versus-host disease (GVHD) is a significant complication
      after allogeneic stem cell transplantation (SCT) and there is no consistent
      information about its characteristics in patients after reduced-intensity
      conditioning regimen FLU/MEL (fludarabine 120 mg/m2 and melphalan 140 mg/m2).
      MATERIAL/METHODS: This was a single-centre prospective observational study of
      patients after allogeneic SCT with FLU/MEL conditioning performed during the
      period 1/2005-12/2007. Characteristics of oral GVHD were observed in 71 patients.
      The observation was discontinued due to death, donor lymphocyte infusion (DLI) or
      new chemotherapy administration. RESULTS: In 10/2010, the median duration of the
      observation of the cohort of the patients was 13 (0.2-69) months, and 42 (35-69)
      months in the still-ongoing 20/71 (28%) patients. Oral acute GVHD had sporadic 7%
      incidence, whereas oral chronic GVHD was observed in 33% of patients and
      persisted with median duration of 188 (11-665) days. Clinical and
      histopathological features were similar in both acute and chronic oral GVHD and
      included mucosal lichenoid changes, erythema, ulcerations and pseudomembranes,
      satellite necrosis, apoptotic bodies and lichenoid interface inflammation.
      CONCLUSIONS: It is necessary to consider complex clinical symptomatology and
      pathological correlations when classifying the oral GVHD, because local oral
      symptoms and histopathological features in both acute and chronic oral GVHD forms
      can be similar. Even though the oral chronic GVHD was mild in the majority of
      patients, it can be considered as clinically significant due to its incidence,
      duration and symptomatology. The FLU/MEL conditioning regimen should not be
      considered as low-risk protocol in this context.

PMID- 21873944
TI  - Effectiveness of ranibizumab intravitreal injections for exudative age-related
      macular degeneration treatment: 12-month outcomes.
AB  - BACKGROUND: The aim of this paper was to evaluate functional and anatomical
      results of intravitreal ranibizumab injections and the course of exudative age
      related macular degeneration (AMD) treatment over a 12-month observation period.
      MATERIAL/METHODS: In 25 patients with active dominantly classic exudative AMD,
      treatment was performed according to the following schedule: 3 intravitreal
      injections of 0.5 mg ranibizumab at monthly intervals (saturation phase); further
      injections were based on activity of the neovascular process. Changes in VA and
      central retinal thickness (CRT) during treatment were evaluated with ANOVA
      testing. RESULTS: Mean pre-treatment best corrected visual acuity was 0.73+/-0.27
      logMAR. After the third ranibizumab injection the best results, 0.54+/-0.27
      logMAR, were seen; 12-month results were 0.58+/-0.26 logMAR. Patients had a mean
      improvement of 10.6 letters at 12 months. In 92% of patients stabilization or
      improvement of vision was observed. The mean number of injections in the 12-month
      period was 6. Baseline mean CRT was 351.12+/-74.15 um. After the first
      ranibizumab injection it decreased significantly to 221.96+/-60.85 um, after the
      third injection it was 200.80+/-47.63 um, and after 12 months it was 213.16+/
      44.37 um. Mean correlations between baseline average CRT and baseline average VA
      measured in ETDRS letters (p=0.017) and in logMAR scale (p=0.033) and between
      average CRT after the third injection and average VA in logMAR scale after the
      third injection (p=0.047) were noted. CONCLUSIONS: Treatment with intravitreal
      ranibizumab injections according to the presented scheme provides AMD patients
      with a chance of stabilization and improvement of the topical state, with a lower
      number of injections and preserved topical and general safety. Our results
      suggest that regular monthly controls are necessary to be able react rapidly to
      the smallest signs of deterioration, not only in visual acuity, but also in OCT
      images.

PMID- 21873945
TI  - Biochemical oxidative stress-related markers in patients with obstructive sleep
      apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a condition contributing to
      oxidative stress. The aim of this study was to ascertain if there is any
      connection between OSA and novel oxidative stress-related markers. Matrix
      metalloproteinases 2 and 9 (MMP-2, MMP-9), high sensitive C-reactive protein
      (hsCRP), pregnancy-associated plasma protein-A (PAPP-A), soluble receptors for
      advanced glycation end-products (sRAGE), zinc (Zn) and copper (Cu) were measured.
      Further biochemical markers were evaluated. MATERIAL/METHODS: Fifty-one men
      suspected for OSA indicated for night polygraphy were included. Apnea/hypopnea
      index (AHI), oxygen desaturation index (ODI), mean blood hemoglobin oxygen
      saturation (SpO2) and time of blood hemoglobin oxygen saturation below 90% (SpO2
      <90%) were measured. Morning venous blood samples were taken. RESULTS: For body
      mass index (BMI) we found strong positive correlation with levels of Cu, MMP-9,
      hsCRP and fibrinogen, and negative correlation with sRAGE. Concerning ventilation
      parameters, we found positive correlation of ODI and SpO2 <90% with markers MMP-9
      and hsCRP. sRAGE level correlated with AHI and ODI negatively. SpO2 correlated
      negatively with Cu, MMP-9, hsCRP and fibrinogen. There was no correlation between
      ventilation parameters and markers MMP-2, PAPP-A and Zn. Compared to severity of
      OSA, there was significant difference in levels of hsCRP and Cu between patients
      with AHI <=5 and AHI >=30 independent of BMI. CONCLUSIONS: MMP-9, hsCRP, sRAGE
      and Cu seem to be strong predictors of oxidative stress in OSA patients. The
      strong correlation between oxidative stress-related markers and OSA is elucidated
      by connection of these to BMI, which is probably a primary condition of oxidative
      stress, but OSA is an additive condition.

PMID- 21873946
TI  - The concentration of thiobarbituric acid reactive substances (TBARS) and
      paraoxonase activity in blood of patients with osteoarthrosis after
      endoprosthesis implantation.
AB  - BACKGROUND: The aim of this study was to evaluate the concentration of
      malondialdehyde (MDA) in erythrocytes and in blood plasma and the activity of
      blood paraoxonase (PON1) of patients with osteoarthrosis (OA) submitted to
      endoprosthesis implantation for evaluating oxidative stress. MATERIAL/METHODS:
      Study was conducted on 55 patients with OA and on 54 total movement-efficient
      volunteers. The material for the study was venous blood plasma, serum and
      erythrocytes. RESULTS: Increased concentration of MDAe before surgery was
      observed in the group of men and in patients with a degenerative process
      affecting hip joints. After an implantation of endoprosthesis, MDAe decreased to
      the level observed in the control groups. In the study group MDA concentration in
      plasma was slightly lower before surgery, and after an operation it reached the
      value of the parameter of the reference groups. Regardless of sex or age,
      paraoxonase activity was almost twice as high in almost all subgroups as in the
      reference group. A positive correlation between PON 1 activity and MDAe
      concentration was demonstrated both before and after surgery in the group of men.
      CONCLUSIONS: The increase of PON1 activity in patients' serum in relation to the
      control groups indicates a probable pathogenic role of the increased formation of
      reactive oxygen species in the course of OA and may suggest acute inflammation of
      the synovial joint. The high level of PON 1 activity after endoprosthesis
      implantation indicates that surgical treatment may additionally stimulate ROS
      generation. MDAe concentration indicate more intensive process of lipid
      peroxidation in the elderly.

PMID- 21873947
TI  - Carpal tunnel syndrome in hemodialysis patients as a dialysis-related amyloidosis
      manifestation--incidence, risk factors and results of surgical treatment.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common complication of
      dialysis-related amyloidosis (DRA) developing in patients on long-term dialysis
      therapy. The aim of this study was to evaluate the incidence of CTS and identify
      factors influencing the development of CTS in patients on maintenance
      hemodialysis, as well as results of its surgical treatment. MATERIAL/METHODS: The
      study included 386 patients, among whom CTS was diagnosed in 40 patients (10.4%)
      on the basis of signs and physical symptoms, as well as by nerve conduction. The
      group of patients with CTS and the group of patients without CTS were compared
      according to age (mean 54.50 vs. 56.48 years) and duration of dialysis treatment.
      Initial analysis of CTS incidence by sex, presence of anti-HCV antibodies, and
      location of arterio-venous fistula (AV fistula) was undertaken. RESULTS: Duration
      of dialysis treatment was the statistically significant risk factor for the
      development of CTS (16.05 vs. 4.51 years; p<0.0001). Among patients treated for a
      long period on hemodialysis (20-30 years), 100% required surgical release
      procedures, while 66.66% of those treated for 15-19 years, 42.1% of those treated
      for 10-14 years, and 1.6% of those treated for less than 10 years. CTS was
      diagnosed more often in anti-HCV-positive patients as compared with anti-HCV
      negative patients (47.5 vs. 6.9%; p<0.0001). No significant differences were
      found when comparing CTS incidence by sex or between the development of CTS
      requiring surgical release intervention and location of the AV fistula.
      CONCLUSIONS: Surgical release procedure of the carpal tunnel gave good treatment
      results in patients with CTS.

PMID- 21873948
TI  - An evaluation of the strategic approach to the rehabilitation of traumatic brain
      injury (TBI) patients.
AB  - BACKGROUND: The objective of our study was to evaluate a goal-driven strategic
      plan for the step-by-step rehabilitation of traumatic brain injury (TBI)
      patients, with effectiveness measured in terms of quality of life, as compared to
      patients treated according to a standard, progressive rehabilitation program.
      MATERIAL/METHODS: We studied 40 patients after TBI awakened from a long-term
      coma. The patients were divided into two equal groups: a control group (n=20)
      involving patients treated before the introduction of the strategic approach, and
      an experimental group (n=20) involving patients rehabilitated under the strategic
      approach. In evaluating the effectiveness of rehabilitation we used a structured
      interview with clinical observation and a scale for assessing the quality of life
      of patients after TBI. RESULTS: The deterioration in the quality of life of TBI
      patients is mainly related to difficulties in satisfying physiological needs,
      self-care, reduced mobility and disorders of cognitive, regulatory, and social
      functions. In both groups, the feature most susceptible to rehabilitation related
      change was movement, while the least susceptible functions were associated with
      the use of different means of transport. This change is significantly greater in
      persons in the experimental group, as compared to controls. CONCLUSIONS: We found
      that a rehabilitation program controlled by a strategic plan, with the
      cooperation of the patient, is more effective in improving the quality of life,
      as the patient is more self-motivated to individually designed objectives.

PMID- 21873949
TI  - The impact of laser irradiation on global stability in patients with
      vertebrobasilar insufficiency: a clinical report.
AB  - BACKGROUND: The purpose of our experiment was to determine whether laser
      stimulation can improve microcirculation in the posterior regions of the brain in
      patients with vertebrobasilar insufficiency (VBI). MATERIAL/METHODS: We studied
      25 patients (20 female, 5 male, mean age 64) diagnosed with chronic VBI. All were
      evaluated using the De Klyn test, followed by qualitative assessment of stability
      using a Berg Balance Scale and evaluation of global stability using an electronic
      balance platform. A CTL-1100 low power laser was used with standard parameters.
      We established a protocol for laser irradiation at 5 points along the vertebral
      artery in the cervical region bilaterally. Irradiation was performed 10 times
      over two weeks. RESULTS: Significant improvement occurred after therapy in
      headache (p=0.0005), vertigo (p<0.0000), and tinnitus (p=0.0387). No significant
      differences were observed in nausea or nystagmus caused by head rotation. The
      Berg Balance Scale results showed significant differences in almost all features.
      There was a tendency towards improved stability in all parameters, and
      statistically significant differences in the total surface of support and the
      spread surface of support for the left foot. CONCLUSIONS: Laser stimulation as
      applied in this study can be useful in the treatment of patients with VBI. The
      main reason for improvement in global stability, balance, and other VBI symptoms
      is better blood perfusion.

PMID- 21873950
TI  - Effect of physiotherapy on the strength of tibial internal rotator muscles in
      males after anterior cruciate ligament reconstruction (ACLR).
AB  - BACKGROUND: The goal of this study was to evaluate the effect of physiotherapy on
      the strength of muscles responsible for tibial internal rotation (IR) in male
      patients after anterior cruciate ligament reconstruction (ACLR) using autografts
      of the semitendinosus and gracilis muscles (STGR). MATERIAL/METHODS: Fifty-nine
      males were examined. The first group consisted of 19 patients subjected to 4
      stage physiotherapy following ACLR. The second group consisted of 20 males
      without knee injuries. The third group consisted of 20 males who had not
      undergone systematic physiotherapy within the last 12 months following lower limb
      injuries. Moments of maximal strength (MMS), isometric torque (IT), and peak
      torque (PT) were measured under static and isokinetic conditions using the Humac
      Norm System. In the first group, IT measurements were performed during the 13th
      and 21st week of physiotherapy, while PT measurements were performed during the
      16th and 21st weeks of physiotherapy following ACLR. In the control groups (II
      and III) the measurements were performed once. RESULTS: In the first group, the
      IT (13 weeks) and PT (16 weeks) values of internal tibial rotator muscles,
      obtained from the operated extremities were significantly lower than the values
      obtained from the uninvolved knees and the control group results. During the 21st
      week of physiotherapy, the results obtained for IT and PT in patients after ACLR
      were similar to the values obtained from the uninvolved knees and the results of
      the second group subjects. CONCLUSIONS: The 21-week physiotherapy in ACLR
      patients favorably affected the PT values of tibial rotator muscles of the
      operated knees. In the third group, the IT values did not indicate a complete
      improvement after 12 months without systematic physiotherapy.

PMID- 21873952
TI  - Whole blood transfusion in the treatment of an acute organophosphorus poisoning-
      a case report.
AB  - BACKGROUND: Organophosphorus compounds (OP) are a group of substances used in
      agriculture as pesticides and are also used as military poisoning agents (MPA).
      Intoxication by these agents may cause severe systemic disturbances related to
      both the exposure time and lethal agent concentration. Toxic effects result from
      an excess of the endogenous neurotransmitter, acetylcholine (ACh), because
      decomposition of Ach by cholinesterases is blocked by OP. CASE REPORT: The
      authors describe a case in which an acute OP poisoning was managed both
      conventionally and with cholinesterase substitution by blood transfusion.
      CONCLUSIONS: Whole blood transfusion could be beneficial in the treatment of
      these life-threatening medical conditions.

PMID- 21873951
TI  - The re-infection rate of high-risk HPV and the recurrence rate of vulvar
      intraepithelial neoplasia (VIN) usual type after surgical treatment.
AB  - BACKGROUND: VIN usual type appears to be related to the HPV's oncogenic types.
      The aim of this prospective multicenter study was to evaluate the re-infection
      rate of high-risk HPV and the recurrence rate of VIN usual type after surgical
      treatment. MATERIAL/METHODS: The study enrolled 103 women affected by VIN usual
      type. They underwent wide local excision by CO2 laser. The patients were
      investigated by clinical evaluation and HPV DNA test 6 months after surgical
      treatment, and then were followed-up at 12, 18, 24, and 36 months. The
      recurrences were treated with re-excision. RESULTS: The rate of HPV infection
      after surgical treatment was 34% at 6 months, 36.9% at 12 months, 40% at 18
      months, 41.7% at 24 months and 44.7% at 36 months. The mean time from HPV
      infection to the development of VIN was 18.8 months. CONCLUSIONS: HPV testing in
      the follow-up of VIN usual type patients might be useful for identifying those
      patients with a higher risk of recurrence after surgical treatment, although more
      studies are needed. These preliminary data suggest that the test, in addition to
      clinical examination, can improve the efficacy of the follow-up.

PMID- 21873953
TI  - Autonomic dysregulation as a novel underlying cause of mitral valve prolapse: a
      hypothesis.
AB  - Mitral valve prolapse is a common valvular abnormality that is caused by
      myxomatous degeneration, characterized macroscopically by leaflet thickening and
      redundancy accompanied with histologically marked proliferation of the spongiosa
      and mucopolysaccharide acid replacement of leaflet collagen in the prolapse
      leaflets. Nevertheless, the discrepant natural history and various concomitant
      syndromes cannot be explained completely by the current genetic autosomal
      dominant inheritance theory. In addition, autonomic dysregulation has been
      commonly reported in mitral valve prolapse, but has never been indicated as a
      major underlying cause. This article attempts to interpret the occurrence of
      primary pathology and progression in mitral valve prolapse on a common basis of
      improper autonomic tone. The imbalanced background of autonomic nervous firing
      leads to disharmonized synthetic/catabolism balance in the extracellular matrix,
      disrupted transition in the interstitial cellular component and invalided anti
      inflammatory pathway in the endothelium, which trigger and accelerate the
      progression of this condition. Such a hypothesis not only unifies the seemingly
      disparate syndromes and valvular disorder, but also has implications for future
      biopharmaceutical and mechanical treatment.

PMID- 21873954
TI  - High frequency yoga breathing increases energy -expenditure from carbohydrates.
      Comment to: Assessment of sleep patterns, energy expenditure and circadian
      rhythms of skin temperature in patients with acute coronary syndrome Hadil Al
      Otair, Mustafa Al-shamiri, Mohammed Bahobail, Munir M. Sharif, Ahmed S. BaHammam
      Med Sci Monit, 2011; 17(7): CR397-403.

PMID- 21873955
TI  - Computer software tool for heart rate variability (HRV), T-wave alternans (TWA)
      and heart rate turbulence (HRT) analysis from ECGs.
AB  - BACKGROUND: This paper presents a software package for quantitative evaluation of
      heart rate variability (HRV), heart rate turbulence (HRT), and T-wave alternans
      (TWA) from ECG recordings. The software has been developed for the purpose of
      scientific research rather than clinical diagnosis. MATERIAL/METHODS: The
      software is written in Matlab Mathematical Language. Procedures for evaluation of
      HRV, HRT and TWA were implemented. HRV analysis was carried out by applying
      statistical and spectral parametric and nonparametric methods. HRT parameters
      were derived using the Schmidt algorithm. TWA analysis was performed both in
      spectral and in time domain by applying Poincare mapping. A flexibility of
      choosing from a number of classical modelling approaches and their modifications
      was foreseen and implemented. The software underwent preliminary verification
      tests both on ECGs from the Physionet online ECG signal repository and recordings
      taken at the Department of Electrocardiology of the Medical University Hospital
      in Lodz. RESULTS: The result of the research is a program enabling simultaneous
      analysis of a number of parameters computed from ECG recordings with the use of
      the indicated analysis methods. The program offers options to preview the
      intermediate results and to alter the preprocessing steps. CONCLUSIONS: By
      offering the possibility to cross-validate the results of analyses obtained by
      several methods and to preview the intermediate analysis steps, the program can
      serve as a helpful aid for clinicians in comprehensive research studies. The
      software tool can also be utilized in training programs for students and medical
      personnel.

PMID- 21873956
TI  - A comparison of the effect of a variety of thermal and vibratory modalities on
      skin temperature and blood flow in healthy volunteers.
AB  - BACKGROUND: Circulation plays an essential role in tissue healing. Moist heat and
      warm water immersion have been shown to increase skin circulation; however, these
      heating modalities can cause burns. Recent research has shown that passive
      vibration can also increase circulation but without the risk of burns.
      MATERIAL/METHODS: The aim of this study is to compare the effects of short
      duration vibration, moist heat, and a combination of the two on skin blood flow
      (SBF) and skin temperature (ST). Ten (10) subjects, 5 female and 5 male, aged 20
      30 years of age, received two interventions a day for 3 consecutive days:
      Intervention 1--Active vibration only (vibration exercise), Intervention 2-
      passive vibration only, Intervention 3--moist heat only, Intervention 4--passive
      vibration combined with moist heat, Intervention 5--a commercial massaging
      heating pad, and Intervention 6--no intervention, resting in supine only
      (control). SBF and ST were measured using a laser Doppler imager during the 10
      minute intervention and then throughout the nine minute recovery period. RESULTS:
      The mean skin blood flow following a ten-minute intervention of the combination
      of passive vibration and moist heat was significantly different from the control,
      active vibration, and the commercial massaging heating pad. Skin temperature
      following the ten-minute interventions of moist heat alone and passive vibration
      alone were both significantly different from the commercial massaging heating pad
      and active vibration interventions. CONCLUSIONS: The combination of passive
      vibration and moist heat produced the greatest increase in skin blood flow and
      the second highest increase in skin blood flow nine minutes post application.

PMID- 21873957
TI  - Phenotypic and genotypic evaluation of fluoroquinolone resistance in clinical
      isolates of Staphylococcus aureus in Tehran.
AB  - BACKGROUND: Fluoroquinolones are broad-spectrum antibiotics widely used in the
      treatment of bacterial infections such as Staphylococcus aureus isolates.
      Resistance to these antibiotics is increasing. MATERIAL/METHODS: The occurrence
      of mutations in the grlA and gyrA loci were evaluated in 69 fluoroquinolone
      resistant S. aureus isolates from 2 teaching hospitals of Tehran University of
      Medical Sciences. RESULTS: Out of the 165 S. aureus isolates, 87 (52.7%) were
      resistant to methicillin and 69 (41.8%) were resistant to fluoroquinolone.
      Fluoroquinolone-resistant S. aureus isolates had a mutation at codon 80 in the
      grlA gene and different mutational combinations in the gyrA gene. These
      mutational combinations included 45 isolates at codons 84 and 86, 23 isolates at
      codons 84, 86 and 106 and 1 isolate at codons 84, 86 and 90. Fluoroquinolone
      resistant S. aureus isolates were clustered into 33 PFGE types. CONCLUSIONS: The
      findings of this study show that the fluoroquinolone-resistant S. aureus strains
      isolated in the teaching hospitals in Tehran had multiple mutations in the QRDRs
      region of both grlA and gyrA genes.

PMID- 21873958
TI  - Contrast-induced nephropathy--a review of current literature and guidelines.
AB  - The use of iodine-based contrast agents always entails the risk of contrast
      induced nephropathy (CIN). The recently observed dramatic increase in the number
      of examinations and therapeutic procedures using iodine-based contrast media led
      us to conduct a thorough analysis of the growing number of scientific reports and
      collective works devoted to contrast-induced nephropathy, based on current
      definitions, epidemiology, pathophysiology, risk factors, successful prophylaxis
      and guidelines of the European Society of Urogenital Radiology (ESUR).
      Radiological contrast agents are the third most common cause of nephropathy among
      in-patients, accounting for 11-12% of cases. CIN is connected with some
      clinically significant consequences, including increased morbidity, prolonged
      hospitalisation, increased risk of complications, potential need for dialysis and
      increased mortality rate. A significant increase in the number of examinations
      applying iodine-based contrast media in the course of inpatient procedures
      requires close cooperation of the clinician and radiologist, supported by
      knowledge of all CIN issues. In order to protect patients from contrast-induced
      nephropathy, it is necessary to monitor their renal function, indentify patients
      with risk factors, refer patients for examinations in a responsible manner, and
      undertake successful preventive measures.

PMID- 21873959
TI  - Serotonin reuptake inhibitor antidepressants (SSRIs) against atherosclerosis.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are a class of drug widely used
      for treatment of mood disorders, including depression and cardiovascular disease.
      A search for related articles in the PubMed database was attempted. It covered
      studies, reports, reviews and editorials of the last 5 years. Pro-inflammatory
      cytokines, such as TNF-alpha, IL-1 and IL-6, stimulate central serotonin (5-HT)
      neurotransmission and are over-expressed in depression, which has been linked
      with hypothalamic-pituitary-adrenal axis (HPA) hyperactivity. They have also been
      implicated in the pathogenesis and progression of other stress-induced disorders,
      like myocardial infarction (MI) and coronary heart disease (CHD), as they seem to
      modulate cardiovascular function by a variety of mechanisms. Biological
      mechanisms like these may explain the link between depression and CHD. There are
      a variety of environmental factors as well as genetic factors that might
      influence the pharmacogenetics of antidepressant drugs. New generation selective
      serotonin reuptake inhibitor antidepressants (SSRIs) causing a reduced
      cardiovascular morbidity and mortality may be related to serotonin platelet
      abnormalities in depressed patients that are effectively treated by SSRIs. SSRIs
      such as fluoxetine, paroxetine, sertraline and citalopram are not only considered
      to be free from the cardiotoxicity of their predecessors but also to function as
      safe and efficacious agents against depression, platelet activation,
      atherosclerosis and development and prognosis of coronary heart disease. However,
      there is a need for more studies in order to establish the exact biochemical
      mechanisms that are responsible for these diseases and the immunoregulatory
      effects of chronic use of SSRI medications.

PMID- 21873961
TI  - Minimally invasive pancreatic surgery of the entire gland: initial experience.
AB  - Many pancreatic cancer surgeons have been slow to adopt minimally invasive
      pancreatic surgery (MIPS) due a lack of formalized minimally invasive training
      and the perceived difficulty in dissecting pancreatic tumors and tissue away from
      the superior mesenteric vessels and consequent concerns for adequacy of oncologic
      margins and lymph node retrieval. A review of the first 29 MIPS procedures for
      malignant and premalignant tumors of the pancreas with the aid of a sterilizeable
      robotically-controlled camera holder was undertaken. As opposed to other robots
      currently available, this device allows for hand-assistance by the operating
      surgeon. Fourteen minimally invasive distal pancreatectomies (MIDP) (10
      laparoscopic, 3 hand-assisted, 1 converted to open), 13 MIPDs (6 laparoscopic, 5
      hand-assisted, 2 converted to open), and 2 laparoscopic central pancreatectomies
      have been performed. Seventeen (59%) of these patients were treated for cancer.
      Of these, 11 underwent a MIPD and 6 a MIDP. There were postoperative
      complications in seven patients (24%) at 30 days. Thirty and 90 day mortality was
      3%. A sterilizeable robotically-controlled laparoscope holder that enables the
      operating surgeon to remain in contact with the patient and have the option of a
      hand-assisted approach may be particularly helpful for minimally invasive
      approaches to malignant and premalignant pancreatic tumors.

PMID- 21873960
TI  - Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders.
AB  - Dopamine receptors control neural signals that modulates behavior. Dopamine plays
      an important role in normal attention; that is the reason for studying the genes
      of the dopaminergic system, mainly in connection with disorders of attention.
      DRD4 influences the postsynaptic action of dopamine and is implicated in many
      neurological processes, exhibits polymorphism and is one of the most studied
      genes in connection with psychiatric disorders. Associations were found with ADHD
      (attention deficit hyperactivity disorder), substance dependences, several
      specific personality traits, and reaction to stress. These findings have
      implications for pharmacogenetics. This article reviews the principle published
      associations of DRD4 variants with psychiatric disorders.

PMID- 21873962
TI  - A current update on the evolution of robotic liver surgery.
AB  - Laparoscopic liver surgery has evolved significantly over the past decade.
      Increasing understanding of hepatic anatomy and advancements in technology have
      extended the scope of the minimally invasive approach. Robotic-assisted
      technology offers solutions to the fundamental limitations of conventional
      laparoscopic liver resection. Several centers have begun to utilize robotic
      technology to perform complex liver surgeries. The purpose of this review is to
      provide a comprehensive analysis of published literature about the role of
      robotic-assisted laparoscopic technology in liver surgery. A literature search of
      Pubmed was used to identify all English publications about robotic liver surgery.
      Publications were selected to examine all unique patient series. Outcomes
      analyzed included operative time, estimated blood loss, length of stay,
      complication rate, conversion rate to open, cost, and oncologic outcomes. A total
      of eight series containing 134 unique patients were selected for review. Sixty
      nine percent of patients had malignant lesions resected, while 31% had benign
      lesions. Segmentectomy/wedge (36%) was the most common resection performed,
      followed by left lateral sectionectomy (28%) right hepatectomy (16%) and left
      hepatectomy (9%). A meta-analysis of the remaining data was not possible due to
      heterogeneity in methods for reporting. Outcomes varied widely between studies.
      Based on analysis of early published series, robotic liver surgery is a feasible
      and safe tool for the minimally invasive resection of hepatic lesions. Further
      evaluation is required to assess for improvement in outcomes, and long-term
      oncologic outcomes are still pending.

PMID- 21873963
TI  - Pancreaticojejunostomy vs. pancreaticogastrostomy following
      pancreaticoduodenectomy: results of comparative study.
AB  - AIM: Several techniques have been proposed for reconstructing pancreatico
      digestive continuity, which the first goal is reducing the rate of pancreatic
      leakage after pancreaticoduodenectomy. Only a limited number studies have been
      carried out. Our objective is to compare the results of pancreaticojejunostomy
      versus pancreaticogastrostomy following pancreaticoduodenectomy. METHODS: This is
      a retrospective and comparative study about 80 patients who underwent
      pancreaticoduodenectomy. These patients were divided into two groups:
      pancreaticojejunostomy (group PJ) and pancreaticogastrostomy (group PG). RESULTS:
      The PJ group included 39 patients, while 41 patients were included in the PG
      group. There were no differences between the two groups concerning: patients'
      demographics, risk factors, indication, mean duration of surgery, texture of
      pancreatic tissue, need for intraoperative blood transfusion and postoperative
      prophylactic octreotide. Overall, the mortality postoperative rate was 7.5%
      (N.=6), the incidence of surgical complications was 50% (51.3% in PJ, 48.8% in
      PG; P=0.823, not significant). Pancreatic fistula was the most frequent
      complication, occurring in 17.5% of patients (25.6% in PJ and 9.8% in PG;
      P=0.062, almost significant). 7.7% of patients who underwent PJ and 14.6% of
      patients who underwent PG required a second surgical intervention (P=0.326, not
      significant). There were no differences between the two groups PG and PJ
      concerning: Postoperative hemorrhage (P=0.63), biliary fistula (P=0.09), acute
      pancreatitis (P=0.95), delayed gastric emptying (P=0.33). The mean postoperative
      hospitalisation period stay was similar in both groups (P=0.63) CONCLUSION: There
      were not any significant differences between the two groups in the overall
      postoperative complication rate, the incidence of postoperative haemorrhage,
      biliary fistula, acute pancreatitis, and delayed.

PMID- 21873964
TI  - Total mesorectal excision with radiofrequency in rectal cancer: open versus
      laparoscopy approach.
AB  - AIM: The aim of this study was to compare the safety, efficacy and oncologic
      results in the low rectal resection with total mesorectal excision with
      radiofrequency (LigasureTM, Covidien, Boulder, CO, USA) in laparoscopic surgery.
      METHODS: From July 2005 to December 2008, 227 patients underwent colorectal
      resection for cancer at S. Martino Hospital in Genoa. Sixty-one patients
      underwent curative rectal resection for mid or low rectal cancer using LigasureTM
      device applied on smaller vessels and for the execution of total mesorectal
      excision. Forty-six patients underwent open laparotomy (OL), 15 laparoscopic
      surgery. There were no differences concerning demographics data and diagnosis,
      but only regarding staging (P=0.009). Primary goal was to evaluate major
      complications, operating time, hospital stay, distal margin of the tumor and
      number of nodes harvested in specimen. Secondary goal was to assess the average
      time of survival in the short period. RESULTS: The mean operative times were
      shorter in the OL group (188 vs. 246 min) overall. This difference was
      significant (P=0.004). In particular two parameters of specimens were analyzed:
      the total number of nodes and distal clearing from cancer, excluding
      abdominoperineal resection. An average number of 16.6 nodes in the OL group and
      13.9 in the VL group (P=ns) were detected; mean distal clearing in the OL group
      was 30.7 mm and 48.1 mm in the VL group (P=ns). There were no differences
      concerning major complications in either group. The hospital stay in the VL group
      was shorter than in the OL group, but the differences were not significant.
      CONCLUSION: The LigasureTM device does not reduce operating time in laparoscopy
      rectal cancer resection but it allows to get correct oncologic results in
      patients submitted to total mesorectal excision.

PMID- 21873965
TI  - Management of axillo-subclavian arterial injuries and predictors of outcome.
AB  - AIM: Although incidence of subclavian and axillary artery injury account for less
      than 9% of all vascular injuries, trauma to these vessels presents a surgical
      challenge particularly with high mortality and morbidity rates. The aim of the
      study was to review our experience on subclavian and axillary vessels injury and
      to analyze factors that may influence results of reconstructive surgery. METHODS:
      Data of 35 patients have been recorded between January 2000 and June 2010. Mean
      age was 24.86 +/- 8.99 years and most were males (88.57%). Regression analysis
      was performed to find out factors affecting outcome. The mean follow-up time was
      60 months. The artery was injured in 32 of the 35 cases (91.43%) and the vein was
      injured in nine cases (25.71%). RESULTS: Seven of 24 reconstructions with
      saphenous graft failed as a result of thrombosis, whereas all of seven prosthetic
      grafts were patent during the long-term follow-up period. Except one, all
      surgical interventions followed by warfarin administration were patent while
      seven repair failures occurred among the anticoagulation-free interventions.
      CONCLUSION: Autologous vein graft must be the first choice; however, in case of
      size discrepancy, prosthetic graft usage may be an alternative approach and
      postoperative administration of anticoagulants may be considered at least in the
      presence of certain risk factors such as native artery-graft diameter
      discrepancy, thrombus history and prosthetic graft.

PMID- 21873966
TI  - Laparoscopic versus open radical nephrectomy in T1-T2 renal carcinoma: personal 5
      year experience about the oncologic outcome.
AB  - AIM: Since 1990 when it was firstly performed, radical laparoscopic nephrectomy
      has gained wide popularity because of its less morbidity and adequate oncologic
      outcome. The aim of this study was to report our experience about oncologic 5
      year outcome of laparoscopic radical nephrectomy. METHODS: Fifteen patients were
      treated laparoscopically and retrospectively compared to a group of patients
      treated laparotomically, omogeneous for age, stage of disease and comorbidities.
      RESULTS: There was no conversion in the laparoscopic group and duration of both
      procedure showed no statistical difference. Laparoscopic procedures showed less
      intraoperative blood loss, less postoperative ileus, shorter hospitalization and
      less morbidity, all with statistical significance. Overall 5 years survival
      showed no statistical significant difference in the two groups (88.9%
      laparoscopic group vs. 86.2% laparotomic group). CONCLUSION: Laparoscopic radical
      nephrectomy has clear advantages compared to the traditional surgery, especially
      about less morbidity, less blood loss, shorter hospitalization, with an oncologic
      outcome absolutely comparable to the laparotomic procedure. Laparoscopic radical
      nephrectomy is a safe and oncologically adequate surgical procedure with clear
      advantages compared to the its open counterpart, so it must be considered as a
      valid alternative to laparotomic surgery in case of non metastatic T1-T2 kidney
      cancer.

PMID- 21873967
TI  - Plasma cholinesterase correlations in acute surgical and critical illness.
AB  - AIM: The properties of plasma cholinesterase (CHE) are partly undiscovered.
      Equally unknown are the correlations between changes in CHE and other blood
      variables during the acute phase response related to acute surgical and critical
      illness. METHODS: Data from 432 measurements of CHE and other variables performed
      in 92 patients were systematically evaluated and processed by regression
      analysis. RESULTS: There was a strong direct correlation between CHE and albumin
      (r=0.77, P<0.0001). CHE was also directly correlated to cholesterol, iron binding
      capacity, hematocrit, prothrombin activity, and inversely correlated to bilirubin
      and to presence of sepsis or liver dysfunction (P<0.0001 for all).
      Postoperatively CHE decreased to about 60% of the preoperative value, remaining
      directly related to it (r=0.69, P<0.0001), and decreasing further in the presence
      of sepsis or liver dysfunction, with slow reversal of the decrease during
      recovery from illness. In parenterally fed septic patients the decrease in CHE
      was moderated by increasing the amino acid dose (P<0.0001). CONCLUSION: In acute
      surgical and critical illness CHE mostly behaves as a negative acute phase
      reactant, independently of the modifications related to other already known
      factors. This should be taken into account when interpreting the implications of
      decreased CHE in the clinical setting.

PMID- 21873968
TI  - Sleeve resections for the treatment of non-small cell lung cancer.
AB  - Parenchyma-sparing sleeve lobectomies were originally developed as a surgical
      strategy for patients not fit for a pneumonectomy, because of impaired pulmonary
      function. As promising short- and long-term results were demonstrated, sleeve
      lobectomy was accepted as an alternative surgical procedure to pneumonectomy.
      Nowadays, sleeve resections are associated with prolonged long-term survival and
      better quality of life, compared to pneumonectomy. Therefore, sleeve resections
      should be performed for centrally located non-small cell lung cancer (NSCLC)
      whenever technically, anatomically and oncologically possible. In this review, we
      discuss the current status of sleeve resections in the management of NSCLC.

PMID- 21873969
TI  - High-dose hyperfractionated accelerated radiotherapy in non-small cell lung
      cancer.
AB  - The observation that improved local tumour control also results in increased
      survival rates, even in a disease such as non-small cell lung cancer (NSCLC), has
      fuelled the interest in strategies aimed at local tumour eradication. It has been
      demonstrated that a clear dose-response relationship exists for radiotherapy,
      i.e. higher doses of radiation lead to increased local tumour control. However,
      prolongation of the overall treatment time beyond 4-5 weeks renders radiotherapy
      less effective because of increased proliferation of tumour cells. It is
      therefore of interest to deliver as high doses as possible in short overall
      treatment times. An extreme example of this strategy is stereotactic body
      radiotherapy (SBRT), where a few large radiation doses, equalling very high
      biological doses, delivered in a short overall treatment time has resulted in at
      least 90 % tumour control in stage I NSCLC. However, when large volumes or
      critical normal structures such as the main bronchi are in the high-dose
      radiation volumes, more extensive fractionation schedules have been used, such as
      70 Gy in 35 daily fractions of 2 Gy. As the overall treatment time than exceeds 4
      5 weeks, hyperfractionated radiotherapy schedules have been introduced, which all
      delivered 2-3 relatively small fractions per day to total doses that are similar
      to the so-called standard regimen. Several randomized phase III trials and a meta
      analysis based on individual patient data have demonstrated a superior 5-year
      survival with this strategy, without increased side effects. Our group has also
      shown that individualised hyperfractionated accelerated radiotherapy (INDAR)
      makes treatment with curative intent even in patients with large tumour volumes
      possible with few important side effects. Early results of INDAR with concurrent
      chemotherapy or with cetuximab are promising.

PMID- 21873970
TI  - Spontaneous pneumothorax: remaining controversies.
AB  - Despite many guidelines issued by national and professional societies, a detailed
      literature survey between the late 1940s and 2010 clearly demonstrates that
      several aspects of pneumothorax pathogenesis and treatment still remain
      controversial. Related to pathogenesis of primary pneumothorax, the current
      manuscript highlights why further studies are needed to explain 1) mechanism of
      the oxygenation impairment in presence of a large pneumothorax; 2) oxygenation
      differences between age and sex-matched patients with a pneumothorax of the same
      size; and 3) sequence of events in tension pneumothorax. Concerning the overall
      therapeutic approach, video-assisted technology provides a minimally invasive
      operative treatment. For this reason methods of recurrence prevention are now
      shared between interventional pulmonologists and thoracic surgeons. Although a
      significantly higher recurrence rates was reported in patients with primary
      spontaneous pneumothorax after simple pleural drainage versus thoracoscopic talc
      poudrage, (34% and 5% respectively), such a policy is still not widely adopted.
      Certain concerns that relate to the use of talc in relapse prevention are also
      discussed, showing that they are mostly dependent on the type of the talc used.
      Concerning secondary pneumothorax, specificities of different forms related to
      diagnostics and therapeutic approach are also pointed out. Lung tuberculosis as
      the underlying cause is particularly addressed, due to the challenge of the
      timely recognition of specific lesions and prompt initiation of the
      antituberculous medical treatment . Similarly, lung cancer is mentioned as a
      possible underlying cause in patients with delayed lung expansion.

PMID- 21873971
TI  - Intraoperative radiation therapy on pancreatic cancer patients: a review of the
      literature.
AB  - Pancreatic cancer is rarely curable, and the overall survival rate at 5 years is
      under 4%. This study aimed to assess the efficacy, effectiveness and safety of
      intraoperative radiation therapy (IORT) as treatment in pancreatic cancer, by
      means of a systematic review of the literature. We searched Pubmed from 1980
      until 2010 by means of prospective randomized trials. The aim was to assess the
      potential impact of IORT on local control, quality of life and overall survival.
      The search was restricted to articles published in English. IORT offers the
      opportunity to administer high doses of irradiation to areas of neoplastic
      involvement while attempting simultaneously to spare normal tissues in the region
      from potentially damaging radiation exposure. However, the results were not in
      favour of IORT in the case of pancreatic cancer in locally advanced and
      metastatic stages. There is no clear evidence to indicate the IORT as more
      effective than other therapies in treating pancreatic cancer.

PMID- 21873972
TI  - [Video-assisted thoracoscopic surgery for simultaneous spontaneus bilateral
      pneumothorax].

PMID- 21873973
TI  - Perineural spread of prostatic carcinoma presenting as lumbar intradural
      metastasis without bony involvement.

PMID- 21873974
TI  - The role of duplex ultrasonography in surgical treatment of acute progressive
      thrombophlebitis of great saphenous vein.
AB  - AIM: The aim of this paper was to determine the role of ultrasonographic
      examination in acute progressive thrombophlebitis (APT) of great saphenous vein
      (GSV) and its impact in considering indications for urgent surgical treatment.
      MEHODS: In this retrospective study, out of 141 consecutive patients operated due
      to APT of GSV above the knee, 63 were examined by ultrasonography prior surgery.
      RESULTS: Out of 63 operated patients, in 38 duplex ultrasonography (DUS) revealed
      that proximal level of phlebitic process was more than 5 cm higher than the one
      found during physical examination (60.3%). In this group, the mean difference
      between DUS and clinical finding was 8.5+/-3.5 cm. In 25 patients there were no
      differences greater than 5 cm found between DUS and physical examination (39.7%).
      There was statistically highly significant difference between DUS and physical
      examination findings (chi2=6.5, P<0.01). CONCLUSION: This study revealed
      significant difference between ultrasonographic and physical findings in patients
      with APT of GSV. DUS presented as reliable diagnostic method in examining, course
      following and making decision for operative treatment of these patients.

PMID- 21873975
TI  - Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast
      cancer.
AB  - Tumour metastasis suppressors are inhibitors of metastasis but their mechanisms
      of action are generally not understood. We previously showed that the suppressor
      Raf kinase inhibitory protein (RKIP) inhibits breast tumour metastasis in part
      via let-7. Here, we demonstrate an integrated approach combining statistical
      analysis of breast tumour gene expression data and experimental validation to
      extend the signalling pathway for RKIP. We show that RKIP inhibits let-7 targets
      (HMGA2, BACH1) that in turn upregulate bone metastasis genes (MMP1, OPN, CXCR4).
      Our results reveal BACH1 as a novel let-7-regulated transcription factor that
      induces matrix metalloproteinase1 (MMP1) expression and promotes metastasis. An
      RKIP pathway metastasis signature (designated RPMS) derived from the complete
      signalling cascade predicts high metastatic risk better than the individual
      genes. These results highlight a powerful approach for identifying signalling
      pathways downstream of a key metastasis suppressor and indicate that analysis of
      genes in the context of their signalling environment is critical for
      understanding their predictive and therapeutic potential.

PMID- 21873976
TI  - The mechanism of translation initiation on Aichivirus RNA mediated by a novel
      type of picornavirus IRES.
AB  - Picornavirus mRNAs contain IRESs that sustain their translation during infection,
      when host protein synthesis is shut off. The major classes of picornavirus IRESs
      (Types 1 and 2) have distinct structures and sequences, but initiation on both is
      determined by their specific interaction with eIF4G. We report here that
      Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an
      IRES that differs structurally from Type 1 and Type 2 IRESs. Its function
      similarly involves interaction with eIF4G, but its eIF4G-interacting domain is
      structurally distinct, although it contains an apical eIF4G-interacting motif
      similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function
      is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's
      interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV
      IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of
      its initiation codon in a stable hairpin.

PMID- 21873977
TI  - RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating
      interactions with a distal regulatory element.
AB  - The transcription factor RUNX1 is essential to establish the haematopoietic gene
      expression programme; however, the mechanism of how it activates transcription of
      haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel
      insights into RUNX1 function by studying regulation of the human CD34 gene, which
      is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs,
      we identified a novel downstream regulatory element (DRE), which is bound by
      RUNX1 and is necessary for human CD34 expression in long-term (LT)-HSCs.
      Conditional deletion of Runx1 in mice harbouring human CD34 promoter-DRE
      constructs abrogates human CD34 expression. We demonstrate by chromosome
      conformation capture assays in LT-HSCs that the DRE physically interacts with the
      human CD34 promoter. Targeted mutagenesis of RUNX binding sites leads to
      perturbation of this interaction and decreased human CD34 expression in LT-HSCs.
      Overall, our in vivo data provide novel evidence about the role of RUNX1 in
      mediating interactions between distal and proximal elements of the HSC gene CD34.

PMID- 21873978
TI  - The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule
      depolymerization.
AB  - Unlike other kinesins, members of the kinesin-13 subfamily do not move
      directionally along microtubules but, instead, depolymerize them. To understand
      how kinesins with structurally similar motor domains can have such dissimilar
      functions, we elucidated the ATP turnover cycle of the kinesin-13, MCAK. In
      contrast to translocating kinesins, ATP cleavage, rather than product release, is
      the rate-limiting step for ATP turnover by MCAK; unpolymerized tubulin and
      microtubules accelerate this step. Further, microtubule ends fully activate the
      ATPase by accelerating the exchange of ADP for ATP. This tuning of the cycle
      adapts MCAK for its depolymerization activity: lattice-stimulated ATP cleavage
      drives MCAK into a weakly bound nucleotide state that reaches microtubule ends by
      diffusion, and end-specific acceleration of nucleotide exchange drives MCAK into
      a strongly bound state that promotes depolymerization. This altered cycle
      accounts well for the different mechanical behaviour of this kinesin, which
      depolymerizes microtubules from their ends, compared to translocating kinesins
      that walk along microtubules. Thus, the kinesin motor domain is a nucleotide
      dependent engine that can be differentially tuned for transport or
      depolymerization functions.

PMID- 21873979
TI  - G-quadruplex-induced instability during leading-strand replication.
AB  - G-quadruplexes are four-stranded nucleic acid structures whose biological
      functions remain poorly understood. In the yeast S. cerevisiae, we report that G
      quadruplexes form and, if not properly processed, pose a specific challenge to
      replication. We show that the G-quadruplex-prone CEB1 tandem array is tolerated
      when inserted near ARS305 replication origin in wild-type cells but is very
      frequently destabilized upon treatment with the potent Phen-DC(3) G-quadruplex
      ligand, or in the absence of the G-quadruplex-unwinding Pif1 helicase, only when
      the G-rich strand is the template of leading-strand replication. The orientation
      dependent instability is associated with the formation of Rad51-Rad52-dependent X
      shaped intermediates during replication detected by two-dimensional (2D) gels,
      and relies on the presence of intact G-quadruplex motifs in CEB1 and on the
      activity of ARS305. The asymmetrical behaviour of G-quadruplex prone sequences
      during replication has implications for their evolutionary dynamics within
      genomes, including the maintenance of G-rich telomeres.

PMID- 21873980
TI  - Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1
      translocation and activation.
AB  - The activation of the Rac1 GTPase during cell signalling entails its
      translocation from the cytosol to membranes, release from sequestering Rho GDP
      dissociation inhibitors (RhoGDI), and GDP/GTP exchange. In addition to those
      steps, we show here that optimal Rac1 activation during cell signalling requires
      the engagement of a downstream, cytoskeletal-based feedback loop nucleated around
      the cytoskeletal protein coronin 1A and the Rac1 exchange factor ArhGEF7. These
      two proteins form a cytosolic complex that, upon Rac1-driven F-actin
      polymerization, translocates to juxtamembrane areas where it expands the pool of
      activated, membrane-bound Rac1. Such activity requires the formation of an F
      actin/ArhGEF7-dependent physical complex of coronin 1A with Pak1 and RhoGDIalpha
      that, once assembled, promotes the Pak1-dependent dissociation of Rac1 from the
      Rac1/RhoGDIalpha complex and subsequent Rac1 activation. Genetic evidence
      demonstrates that this relay circuit is essential for generating sustained Rac1
      activation levels during cell signalling.

PMID- 21873981
TI  - A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear
      memories.
AB  - Extinction learning refers to the phenomenon that a previously learned response
      to an environmental stimulus, for example, the expression of an aversive
      behaviour upon exposure to a specific context, is reduced when the stimulus is
      repeatedly presented in the absence of a previously paired aversive event.
      Extinction of fear memories has been implicated with the treatment of anxiety
      disease but the molecular processes that underlie fear extinction are only
      beginning to emerge. Here, we show that fear extinction initiates upregulation of
      hippocampal insulin-growth factor 2 (Igf2) and downregulation of insulin-growth
      factor binding protein 7 (Igfbp7). In line with this observation, we demonstrate
      that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an
      IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered
      IGF2 signalling during fear extinction. To this end, we show that fear extinction
      induced IGF2/IGFBP7 signalling promotes the survival of 17-19-day-old newborn
      hippocampal neurons. In conclusion, our data suggest that therapeutic strategies
      that enhance IGF2 signalling and adult neurogenesis might be suitable to treat
      disease linked to excessive fear memory.

PMID- 21873982
TI  - Transplantation: Effect of pancreas-after-kidney transplant on renal graft
      survival.

PMID- 21873983
TI  - Transplantation: Initially intensified mycophenolate dosing reduces rejection
      rates in de novo renal transplant recipients.

PMID- 21873984
TI  - Mechanism of actin filament nucleation by the bacterial effector VopL.
AB  - Vibrio parahaemolyticus protein L (VopL) is an actin nucleation factor that
      induces stress fibers when injected into eukaryotic host cells. VopL contains
      three N-terminal Wiskott-Aldrich homology 2 (WH2) motifs and a unique VopL C
      terminal domain (VCD). We describe crystallographic and biochemical analyses of
      filament nucleation by VopL. The WH2 element of VopL does not nucleate on its own
      and requires the VCD for activity. The VCD forms a U-shaped dimer in the crystal,
      stabilized by a terminal coiled coil. Dimerization of the WH2 motifs contributes
      strongly to nucleation activity, as do contacts of the VCD to actin. Our data
      lead to a model in which VopL stabilizes primarily lateral (short-pitch) contacts
      between actin monomers to create the base of a two-stranded filament.
      Stabilization of lateral contacts may be a common feature of actin filament
      nucleation by WH2-based factors.

PMID- 21873985
TI  - Mechanism of actin filament nucleation by Vibrio VopL and implications for tandem
      W domain nucleation.
AB  - Pathogen proteins targeting the actin cytoskeleton often serve as model systems
      to understand their more complex eukaryotic analogs. We show that the strong
      actin filament nucleation activity of Vibrio parahaemolyticus VopL depends on its
      three W domains and on its dimerization through a unique VopL C-terminal domain
      (VCD). The VCD shows a previously unknown all-helical fold and interacts with the
      pointed end of the actin nucleus, contributing to the nucleation activity
      directly and through duplication of the W domain repeat. VopL promotes rapid
      cycles of filament nucleation and detachment but generally has no effect on
      elongation. Profilin inhibits VopL-induced nucleation by competing for actin
      binding to the W domains. Combined, the results suggest that VopL stabilizes a
      hexameric double-stranded pointed end nucleus. Analysis of hybrid constructs of
      VopL and the eukaryotic nucleator Spire suggest that Spire may also function as a
      dimer in cells.

PMID- 21873986
TI  - Vascular anastomosis using controlled phase transitions in poloxamer gels.
AB  - Vascular anastomosis is the cornerstone of vascular, cardiovascular and
      transplant surgery. Most anastomoses are performed with sutures, which are
      technically challenging and can lead to failure from intimal hyperplasia and
      foreign body reaction. Numerous alternatives to sutures have been proposed, but
      none has proven superior, particularly in small or atherosclerotic vessels. We
      have developed a new method of sutureless and atraumatic vascular anastomosis
      that uses US Food and Drug Administration (FDA)-approved thermoreversible tri
      block polymers to temporarily maintain an open lumen for precise approximation
      with commercially available glues. We performed end-to-end anastomoses five times
      more rapidly than we performed hand-sewn controls, and vessels that were too
      small (<1.0 mm) to sew were successfully reconstructed with this sutureless
      approach. Imaging of reconstructed rat aorta confirmed equivalent patency, flow
      and burst strength, and histological analysis demonstrated decreased inflammation
      and fibrosis at up to 2 years after the procedure. This new technology has
      potential for improving efficiency and outcomes in the surgical treatment of
      cardiovascular disease.

PMID- 21873987
TI  - Peroxisome proliferation-associated control of reactive oxygen species sets
      melanocortin tone and feeding in diet-induced obesity.
AB  - Previous studies have proposed roles for hypothalamic reactive oxygen species
      (ROS) in the modulation of circuit activity of the melanocortin system. Here we
      show that suppression of ROS diminishes pro-opiomelanocortin (POMC) cell
      activation and promotes the activity of neuropeptide Y (NPY)- and agouti-related
      peptide (AgRP)-co-producing (NPY/AgRP) neurons and feeding, whereas ROS-activates
      POMC neurons and reduces feeding. The levels of ROS in POMC neurons were
      positively correlated with those of leptin in lean and ob/ob mice, a relationship
      that was diminished in diet-induced obese (DIO) mice. High-fat feeding resulted
      in proliferation of peroxisomes and elevated peroxisome proliferator-activated
      receptor gamma (PPAR-gamma) mRNA levels within the hypothalamus. The
      proliferation of peroxisomes in POMC neurons induced by the PPAR-gamma agonist
      rosiglitazone decreased ROS levels and increased food intake in lean mice on high
      fat diet. Conversely, the suppression of peroxisome proliferation by the PPAR
      antagonist GW9662 increased ROS concentrations and c-fos expression in POMC
      neurons. Also, it reversed high-fat feeding-triggered elevated NPY/AgRP and low
      POMC neuronal firing, and resulted in decreased feeding of DIO mice. Finally,
      central administration of ROS alone increased c-fos and phosphorylated signal
      transducer and activator of transcription 3 (pStat3) expression in POMC neurons
      and reduced feeding of DIO mice. These observations unmask a previously unknown
      hypothalamic cellular process associated with peroxisomes and ROS in the central
      regulation of energy metabolism in states of leptin resistance.

PMID- 21873988
TI  - Stem cell gene expression programs influence clinical outcome in human leukemia.
AB  - Xenograft studies indicate that some solid tumors and leukemias are organized as
      cellular hierarchies sustained by cancer stem cells (CSCs). Despite the promise
      of the CSC model, its relevance in humans remains uncertain. Here we show that
      acute myeloid leukemia (AML) follows a CSC model on the basis of sorting multiple
      populations from each of 16 primary human AML samples and identifying which
      contain leukemia stem cells (LSCs) using a sensitive xenograft assay. Analysis of
      gene expression from all functionally validated populations yielded an LSC
      specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was
      established. Bioinformatic analysis identified a core transcriptional program
      shared by LSCs and HSCs, revealing the molecular machinery underlying 'stemness'
      properties. Both stem cell programs were highly significant independent
      predictors of patient survival and were found in existing prognostic signatures.
      Thus, determinants of stemness influence the clinical outcome of AML,
      establishing that LSCs are clinically relevant and not artifacts of
      xenotransplantation.

PMID- 21873990
TI  - Graphene oxide windows for in situ environmental cell photoelectron spectroscopy.
AB  - The performance of new materials and devices often depends on processes taking
      place at the interface between an active solid element and the environment (such
      as air, water or other fluids). Understanding and controlling such interfacial
      processes require surface-specific spectroscopic information acquired under real
      world operating conditions, which can be challenging because standard approaches
      such as X-ray photoelectron spectroscopy generally require high-vacuum
      conditions. The state-of-the-art approach to this problem relies on unique and
      expensive apparatus including electron analysers coupled with sophisticated
      differentially pumped lenses. Here, we develop a simple environmental cell with
      graphene oxide windows that are transparent to low-energy electrons (down to 400
      eV), and demonstrate the feasibility of X-ray photoelectron spectroscopy
      measurements on model samples such as gold nanoparticles and aqueous salt
      solution placed on the back side of a window. These proof-of-principle results
      show the potential of using graphene oxide, graphene and other emerging ultrathin
      membrane windows for the fabrication of low-cost, single-use environmental cells
      compatible with commercial X-ray and Auger microprobes as well as scanning or
      transmission electron microscopes.

PMID- 21873991
TI  - The Scherrer equation versus the 'Debye-Scherrer equation'.

PMID- 21873989
TI  - Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor
      through the inhibition of Ido.
AB  - Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal
      tumor (GIST) and produces a clinical response in 80% of patients. The mechanism
      is believed to depend predominantly on the inhibition of KIT-driven signals for
      tumor-cell survival and proliferation. Using a mouse model of spontaneous GIST,
      we found that the immune system contributes substantially to the antitumor
      effects of imatinib. Imatinib therapy activated CD8(+) T cells and induced
      regulatory T cell (T(reg) cell) apoptosis within the tumor by reducing tumor-cell
      expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido).
      Concurrent immunotherapy augmented the efficacy of imatinib in mouse GIST. In
      freshly obtained human GIST specimens, the T cell profile correlated with
      imatinib sensitivity and IDO expression. Thus, T cells are crucial to the
      antitumor effects of imatinib in GIST, and concomitant immunotherapy may further
      improve outcomes in human cancers treated with targeted agents.

PMID- 21873992
TI  - Graphene nanoribbons with smooth edges behave as quantum wires.
AB  - Graphene nanoribbons with perfect edges are predicted to exhibit interesting
      electronic and spintronic properties, notably quantum-confined bandgaps and
      magnetic edge states. However, so far, graphene nanoribbons produced by
      lithography have had rough edges, as well as low-temperature transport
      characteristics dominated by defects (mainly variable range hopping between
      localized states in a transport gap near the Dirac point). Here, we report that
      one- and two-layer nanoribbon quantum dots made by unzipping carbon nanotubes
      exhibit well-defined quantum transport phenomena, including Coulomb blockade, the
      Kondo effect, clear excited states up to ~20 meV, and inelastic co-tunnelling.
      Together with the signatures of intrinsic quantum-confined bandgaps and high
      conductivities, our data indicate that the nanoribbons behave as clean quantum
      wires at low temperatures, and are not dominated by defects.

PMID- 21873993
TI  - Direct observation of a propagating spin wave induced by spin-transfer torque.
AB  - Spin torque oscillators with nanoscale electrical contacts are able to produce
      coherent spin waves in extended magnetic films, and offer an attractive
      combination of electrical and magnetic field control, broadband operation, fast
      spin-wave frequency modulation, and the possibility of synchronizing multiple
      spin-wave injection sites. However, many potential applications rely on
      propagating (as opposed to localized) spin waves, and direct evidence for
      propagation has been lacking. Here, we directly observe a propagating spin wave
      launched from a spin torque oscillator with a nanoscale electrical contact into
      an extended Permalloy (nickel iron) film through the spin transfer torque effect.
      The data, obtained by wave-vector-resolved micro-focused Brillouin light
      scattering, show that spin waves with tunable frequencies can propagate for
      several micrometres. Micromagnetic simulations provide the theoretical support to
      quantitatively reproduce the results.

PMID- 21873994
TI  - Ligand binding to distinct states diverts aggregation of an amyloid-forming
      protein.
AB  - Although small molecules that modulate amyloid formation in vitro have been
      identified, significant challenges remain in determining precisely how these
      species act. Here we describe the identification of rifamycin SV as a potent
      inhibitor of beta(2) microglobulin (beta(2)m) fibrillogenesis when added during
      the lag time of assembly or early during fibril elongation. Biochemical
      experiments demonstrate that the small molecule does not act by a colloidal
      mechanism. Exploiting the ability of electrospray ionization-ion mobility
      spectrometry-mass spectrometry (ESI-IMS-MS) to resolve intermediates of amyloid
      assembly, we show instead that rifamycin SV inhibits beta(2)m fibrillation by
      binding distinct monomeric conformers, disfavoring oligomer formation and
      diverting the course of assembly to the formation of spherical aggregates. The
      results demonstrate the power of ESI-IMS-MS to identify specific protein
      conformers as targets for intervention in fibrillogenesis using small molecules
      and reveal a mechanism of action in which ligand binding diverts unfolded protein
      monomers toward alternative assembly pathways.

PMID- 21873996
TI  - Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers.
AB  - G protein-coupled receptors (GPCRs) transmit signals by forming active-state
      complexes with heterotrimeric G proteins. It has been suggested that some GPCRs
      also assemble with G proteins before ligand-induced activation and that inactive
      state preassembly facilitates rapid and specific G protein activation. However,
      no mechanism of preassembly has been described, and no functional consequences of
      preassembly have been demonstrated. Here we show that M(3) muscarinic
      acetylcholine receptors (M3R) form inactive-state complexes with G(q)
      heterotrimers in intact cells. The M3R C terminus is sufficient, and a six-amino
      acid polybasic sequence distal to helix 8 ((565)KKKRRK(570)) is necessary for
      preassembly with G(q). Replacing this sequence with six alanine residues prevents
      preassembly, slows the rate of G(q) activation and decreases steady-state agonist
      sensitivity. That other G(q)-coupled receptors possess similar polybasic regions
      and also preassemble with G(q) suggests that these GPCRs may use a common
      preassembly mechanism to facilitate activation of G(q) heterotrimers.

PMID- 21873995
TI  - TRPA1 underlies a sensing mechanism for O2.
AB  - Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but
      also elicits toxicity. To understand how animals cope with the ambivalent
      physiological nature of O(2), it is critical to elucidate the molecular
      mechanisms responsible for O(2) sensing. Here our systematic evaluation of
      transient receptor potential (TRP) cation channels using reactive disulfides with
      different redox potentials reveals the capability of TRPA1 to sense O(2). O(2)
      sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs)
      exert O(2)-dependent inhibition on TRPA1 activity in normoxia, direct O(2) action
      overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine
      mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief
      from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the
      Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal
      and sensory neurons and thereby impedes enhancement of in vivo vagal discharges
      induced by hyperoxia and hypoxia. The results suggest a new O(2)-sensing
      mechanism mediated by TRPA1.

PMID- 21873997
TI  - Epigenetics: Targeting leukemia on the DOT.

PMID- 21873999
TI  - Pol III binding in six mammals shows conservation among amino acid isotypes
      despite divergence among tRNA genes.
AB  - RNA polymerase III (Pol III) transcription of tRNA genes is essential for
      generating the tRNA adaptor molecules that link genetic sequence and protein
      translation. By mapping Pol III occupancy genome-wide in mouse, rat, human,
      macaque, dog and opossum livers, we found that Pol III binding to individual tRNA
      genes varies substantially in strength and location. However, when we took into
      account tRNA redundancies by grouping Pol III occupancy into 46 anticodon
      isoacceptor families or 21 amino acid-based isotype classes, we discovered strong
      conservation. Similarly, Pol III occupancy of amino acid isotypes is almost
      invariant among transcriptionally and evolutionarily diverse tissues in mouse.
      Thus, synthesis of functional tRNA isotypes has been highly constrained, although
      the usage of individual tRNA genes has evolved rapidly.

PMID- 21873998
TI  - The genome of the mesopolyploid crop species Brassica rapa.
AB  - We report the annotation and analysis of the draft genome sequence of Brassica
      rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding
      genes in the B. rapa genome, which has undergone genome triplication. We used
      Arabidopsis thaliana as an outgroup for investigating the consequences of genome
      triplication, such as structural and functional evolution. The extent of gene
      loss (fractionation) among triplicated genome segments varies, with one of the
      three copies consistently retaining a disproportionately large fraction of the
      genes expected to have been present in its ancestor. Variation in the number of
      members of gene families present in the genome may contribute to the remarkable
      morphological plasticity of Brassica species. The B. rapa genome sequence
      provides an important resource for studying the evolution of polyploid genomes
      and underpins the genetic improvement of Brassica oil and vegetable crops.

PMID- 21874000
TI  - Germline BAP1 mutations predispose to malignant mesothelioma.
AB  - Because only a small fraction of asbestos-exposed individuals develop malignant
      mesothelioma, and because mesothelioma clustering is observed in some families,
      we searched for genetic predisposing factors. We discovered germline mutations in
      the gene encoding BRCA1 associated protein-1 (BAP1) in two families with a high
      incidence of mesothelioma, and we observed somatic alterations affecting BAP1 in
      familial mesotheliomas, indicating biallelic inactivation. In addition to
      mesothelioma, some BAP1 mutation carriers developed uveal melanoma. We also found
      germline BAP1 mutations in 2 of 26 sporadic mesotheliomas; both individuals with
      mutant BAP1 were previously diagnosed with uveal melanoma. We also observed
      somatic truncating BAP1 mutations and aberrant BAP1 expression in sporadic
      mesotheliomas without germline mutations. These results identify a BAP1-related
      cancer syndrome that is characterized by mesothelioma and uveal melanoma. We
      hypothesize that other cancers may also be involved and that mesothelioma
      predominates upon asbestos exposure. These findings will help to identify
      individuals at high risk of mesothelioma who could be targeted for early
      intervention.

PMID- 21874001
TI  - Genome-wide association study in individuals of South Asian ancestry identifies
      six new type 2 diabetes susceptibility loci.
AB  - We carried out a genome-wide association study of type-2 diabetes (T2D) in
      individuals of South Asian ancestry. Our discovery set included 5,561 individuals
      with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and
      Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4)
      for testing in a replication sample of 13,170 cases and 25,398 controls, also all
      of South Asian ancestry. In the combined analysis, we identified common genetic
      variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly
      associated with T2D (P = 4.1 * 10(-8) to P = 1.9 * 10(-11)). SNPs at GRB14 were
      also associated with insulin sensitivity (P = 5.0 * 10(-4)), and SNPs at ST6GAL1
      and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P
      = 0.001, respectively). Our findings provide additional insight into mechanisms
      underlying T2D and show the potential for new discovery from genetic association
      studies in South Asians, a population with increased susceptibility to T2D.

PMID- 21874002
TI  - Whole-genome sequencing of multiple Arabidopsis thaliana populations.
AB  - The plant Arabidopsis thaliana occurs naturally in many different habitats
      throughout Eurasia. As a foundation for identifying genetic variation
      contributing to adaptation to diverse environments, a 1001 Genomes Project to
      sequence geographically diverse A. thaliana strains has been initiated. Here we
      present the first phase of this project, based on population-scale sequencing of
      80 strains drawn from eight regions throughout the species' native range. We
      describe the majority of common small-scale polymorphisms as well as many larger
      insertions and deletions in the A. thaliana pan-genome, their effects on gene
      function, and the patterns of local and global linkage among these variants. The
      action of processes other than spontaneous mutation is identified by comparing
      the spectrum of mutations that have accumulated since A. thaliana diverged from
      its closest relative 10 million years ago with the spectrum observed in the
      laboratory. Recent species-wide selective sweeps are rare, and potentially
      deleterious mutations are more common in marginal populations.

PMID- 21874003
TI  - Germline mutations in BAP1 predispose to melanocytic tumors.
AB  - Common acquired melanocytic nevi are benign neoplasms that are composed of small,
      uniform melanocytes and are typically present as flat or slightly elevated
      pigmented lesions on the skin. We describe two families with a new autosomal
      dominant syndrome characterized by multiple, skin-colored, elevated melanocytic
      tumors. In contrast to common acquired nevi, the melanocytic neoplasms in
      affected family members ranged histopathologically from epithelioid nevi to
      atypical melanocytic proliferations that showed overlapping features with
      melanoma. Some affected individuals developed uveal or cutaneous melanomas.
      Segregating with this phenotype, we found inactivating germline mutations of
      BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of
      melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various
      somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic
      melanocytic neoplasms showing histological similarities to the familial tumors.
      These findings suggest that loss of BAP1 is associated with a clinically and
      morphologically distinct type of melanocytic neoplasm.

PMID- 21874004
TI  - Spatially controlled simultaneous patterning of multiple growth factors in three
      dimensional hydrogels.
AB  - Three-dimensional (3D) protein-patterned scaffolds provide a more biomimetic
      environment for cell culture than traditional two-dimensional surfaces, but
      simultaneous 3D protein patterning has proved difficult. We developed a method to
      spatially control the immobilization of different growth factors in distinct
      volumes in 3D hydrogels, and to specifically guide differentiation of
      stem/progenitor cells therein. Stem-cell differentiation factors sonic hedgehog
      (SHH) and ciliary neurotrophic factor (CNTF) were simultaneously immobilized
      using orthogonal physical binding pairs, barnase-barstar and streptavidin-biotin,
      respectively. Barnase and streptavidin were sequentially immobilized using two
      photon chemistry for subsequent concurrent complexation with fusion proteins
      barstar-SHH and biotin-CNTF, resulting in bioactive 3D patterned hydrogels. The
      technique should be broadly applicable to the patterning of a wide range of
      proteins.

PMID- 21874005
TI  - Fast control of nuclear spin polarization in an optically pumped single quantum
      dot.
AB  - Highly polarized nuclear spins within a semiconductor quantum dot induce
      effective magnetic (Overhauser) fields of up to several Tesla acting on the
      electron spin, or up to a few hundred mT for the hole spin. Recently this has
      been recognized as a resource for intrinsic control of quantum-dot-based spin
      quantum bits. However, only static long-lived Overhauser fields could be used.
      Here we demonstrate fast redirection on the microsecond timescale of Overhauser
      fields on the order of 0.5 T experienced by a single electron spin in an
      optically pumped GaAs quantum dot. This has been achieved using coherent control
      of an ensemble of 10(5) optically polarized nuclear spins by sequences of short
      radiofrequency pulses. These results open the way to a new class of experiments
      using radiofrequency techniques to achieve highly correlated nuclear spins in
      quantum dots, such as adiabatic demagnetization in the rotating frame leading to
      sub-MUK nuclear spin temperatures, rapid adiabatic passage, and spin squeezing.

PMID- 21874006
TI  - Quantitative proteomics by amino acid labeling in C. elegans.
AB  - We demonstrate labeling of Caenorhabditis elegans with heavy isotope-labeled
      lysine by feeding them with heavy isotope-labeled Escherichia coli. Using heavy
      isotope-labeled worms and quantitative proteomics methods, we identified several
      proteins that are regulated in response to loss or RNAi-mediated knockdown of the
      nuclear hormone receptor 49 in C. elegans. The combined use of quantitative
      proteomics and selective gene knockdown is a powerful tool for C. elegans
      biology.

PMID- 21874007
TI  - Stable-isotope labeling with amino acids in nematodes.
AB  - We describe an approach for accurate quantitation of global protein dynamics in
      Caenorhabditis elegans. We adapted stable-isotope labeling with amino acids in
      cell culture (SILAC) for nematodes by feeding worms a heavy lysine- and heavy
      arginine-labeled Escherichia coli strain and report a genetic solution to
      elminate the problem of arginine-to-proline conversion. Combining our approach
      with quantitative proteomics methods, we characterized the heat-shock response in
      worms.

PMID- 21874008
TI  - Formation of stable attachments between kinetochores and microtubules depends on
      the B56-PP2A phosphatase.
AB  - Error-free chromosome segregation depends on the precise regulation of
      phosphorylation to stabilize kinetochore-microtubule attachments (K-fibres) on
      sister chromatids that have attached to opposite spindle poles (bi-oriented). In
      many instances, phosphorylation correlates with K-fibre destabilization.
      Consistent with this, multiple kinases, including Aurora B and Plk1, are enriched
      at kinetochores of mal-oriented chromosomes when compared with bi-oriented
      chromosomes, which have stable attachments. Paradoxically, however, these kinases
      also target to prometaphase chromosomes that have not yet established spindle
      attachments and it is therefore unclear how kinetochore-microtubule interactions
      can be stabilized when kinase levels are high. Here we show that the generation
      of stable K-fibres depends on the B56-PP2A phosphatase, which is enriched at
      centromeres/kinetochores of unattached chromosomes. When B56-PP2A is depleted, K
      fibres are destabilized and chromosomes fail to align at the spindle equator.
      Strikingly, B56-PP2A depletion increases the level of phosphorylation of Aurora B
      and Plk1 kinetochore substrates as well as Plk1 recruitment to kinetochores.
      Consistent with increased substrate phosphorylation, we find that chemical
      inhibition of Aurora or Plk1 restores K-fibres in B56-PP2A-depleted cells. Our
      findings reveal that PP2A, an essential tumour suppressor, tunes the balance of
      phosphorylation to promote chromosome-spindle interactions during cell division.

PMID- 21874009
TI  - Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex
      driven cytoplasmic streaming in mouse oocytes.
AB  - Mature mammalian oocytes are poised for completing meiosis II (MII) on
      fertilization by positioning the spindle close to an actomyosin-rich cortical
      cap. Here, we show that the Arp2/3 complex localizes to the cortical cap in a Ran
      GTPase-dependent manner and nucleates actin filaments in the cortical cap and a
      cytoplasmic actin network. Inhibition of Arp2/3 activity leads to rapid
      dissociation of the spindle from the cortex. Live-cell imaging and spatiotemporal
      image correlation spectroscopy analysis reveal that actin filaments flow
      continuously away from the Arp2/3-rich cortex, driving a cytoplasmic streaming
      expected to exert a net pushing force on the spindle towards the cortex. Arp2/3
      inhibition not only diminishes this actin flow and cytoplasmic streaming but also
      enables a reverse streaming driven by myosin-II-based cortical contraction,
      moving the spindle away from the cortex. Thus, the asymmetric MII spindle
      position is dynamically maintained as a result of balanced forces governed by the
      Arp2/3 complex.

PMID- 21874010
TI  - The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable
      prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas.
AB  - AKT1 signaling pathway is important for the regulation of protein synthesis and
      cell survival with implications in carcinogenesis. In this study, we explored the
      prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We
      investigated the status of phosphatase and tensin homolog deleted on chromosome
      10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p
      MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation
      factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas
      by immunohistochemistry. Western blot analysis was performed to verify the
      expression levels of p-AKT1 and p-MTOR. The relationship of protein expression
      with clinicopathological data and the correlations of protein expression levels
      were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with
      a better survival in patients with intrahepatic cholangiocarcinoma (P=0.0137,
      0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an
      independent prognostic factor, and p-AKT1 showed tendency (P=0.032 and 0.051,
      respectively). The overexpression of p-MTOR was correlated with well-to
      moderately differentiated tumors (P<0.001) and tumors without metastasis
      (P=0.046). Expression levels of the AKT1 signaling pathway proteins in this study
      showed positive correlations with each other, except for PTEN. Aberrant
      expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were
      associated with a favorable prognosis, possibly in a PTEN-independent manner. Our
      results indicate that dysregulation of the AKT1 pathway may have an important
      role in the development of intrahepatic cholangiocarcinoma, but not necessarily
      in the progression of the disease.

PMID- 21874011
TI  - Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC)
      lesions of the kidney.
AB  - The perivascular epithelioid cell (PEC) is a unique cell type coexpressing
      contractile proteins (mainly alpha-smooth muscle actin), melanocytic markers,
      including microphthalmia-associated transcription factor (MITF), and estrogen and
      progesterone receptors. It is constantly present in a group of tumors called
      PEComas. Renal PEComas include the common angiomyolipoma as well as less common
      lesions such as microscopic angiomyolipoma, intraglomerular lesions,
      angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like
      angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been
      demonstrated that most of these lesions are determined by mutations affecting
      genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous
      sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway,
      and it has been observed that some PEComas regressed during sirolimus therapy, an
      MTOR inhibitor. Recently, overexpression of MITF has been related to the
      expression of the papain-like cysteine protease cathepsin K in osteoclasts where
      it has inhibited MTOR. The aim of this study is to evaluate cathepsin K
      immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The
      study population consisted of 84 renal PEComa lesions, including 5 composed
      predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed
      of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31
      common angiomyolipomas composed of a mixture of fat, spindle and epithelioid
      smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic
      angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8
      epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1
      example of lymphangioleiomyomatosis of the renal sinus. In all of the renal
      PEComas, cathepsin K was found to be constantly and strongly expressed and seems
      to be a more powerful marker than other commonly used markers for their
      identification, especially to confirm the diagnosis on needle biopsies.

PMID- 21874012
TI  - Histopathological and immunohistochemical findings of 20 autopsy cases with 2009
      H1N1 virus infection.
AB  - Twenty autopsy cases with 2009 pandemic influenza A (2009 H1N1) virus infection,
      performed between August 2009 and February 2010, were histopathologically
      analyzed. Hematoxylin-eosin staining, immunohistochemistry for type A influenza
      nucleoprotein antigen, and real-time reverse transcription-PCR assay for viral
      RNA were performed on formalin-fixed and paraffin-embedded specimens. In
      addition, the D222G amino acid substitution in influenza virus hemagglutinin,
      which binds to specific cell receptors, was analyzed in formalin-fixed and
      paraffin-embedded trachea and lung sections by direct sequencing of PCR-amplified
      products. There were several histopathological patterns in the lung according to
      the most remarkable findings in each case: acute diffuse alveolar damage (DAD)
      with a hyaline membrane (four cases), organized DAD (one case), acute massive
      intra-alveolar edema with variable degrees of hemorrhage (three cases),
      neutrophilic bronchopneumonia (five cases) and tracheobronchitis with limited
      histopathological changes in alveoli (four cases). In two cases, the main
      findings were due to preexisting disease. Influenza virus antigen was only
      detected in the respiratory tract in 10 cases by immunohistochemistry. The
      antigen was detected in type II pneumocytes (three cases) in the epithelial cells
      of the trachea, bronchi and glands (six cases), and in the epithelial cells in
      both of the above (one case). The four cases with acute DAD presented with
      antigen-positive type II pneumocytes. In one case, the D222G substitution was
      detected in the lung as a major sequence, although 222D was prominent in the
      trachea, suggesting that selection of the viral clones occurred in the
      respiratory tract. In five cases, the pathogenesis of 2009 H1N1 was confirmed to
      be viral infection in pneumocytes, which caused severe alveolar damage and fatal
      viral pneumonia. Further studies on both host and viral factors in autopsy or
      biopsy materials will be essential to elucidate the other pathogenic factors
      involved in influenza virus infection.

PMID- 21874013
TI  - Neuronal activity modifies the DNA methylation landscape in the adult brain.
AB  - DNA methylation has been traditionally viewed as a highly stable epigenetic mark
      in postmitotic cells. However, postnatal brains appear to show stimulus-induced
      methylation changes, at least in a few identified CpG dinucleotides. How
      extensively the neuronal DNA methylome is regulated by neuronal activity is
      unknown. Using a next-generation sequencing-based method for genome-wide analysis
      at single-nucleotide resolution, we quantitatively compared the CpG methylation
      landscape of adult mouse dentate granule neurons in vivo before and after
      synchronous neuronal activation. About 1.4% of 219,991 CpGs measured showed rapid
      active demethylation or de novo methylation. Some modifications remained stable
      for at least 24 h. These activity-modified CpGs showed a broad genomic
      distribution with significant enrichment in low-CpG density regions, and were
      associated with brain-specific genes related to neuronal plasticity. Our study
      implicates modification of the neuronal DNA methylome as a previously
      underappreciated mechanism for activity-dependent epigenetic regulation in the
      adult nervous system.

PMID- 21874014
TI  - A category-specific response to animals in the right human amygdala.
AB  - The amygdala is important in emotion, but it remains unknown whether it is
      specialized for certain stimulus categories. We analyzed responses recorded from
      489 single neurons in the amygdalae of 41 neurosurgical patients and found a
      categorical selectivity for pictures of animals in the right amygdala. This
      selectivity appeared to be independent of emotional valence or arousal and may
      reflect the importance that animals held throughout our evolutionary past.

PMID- 21874015
TI  - Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in post
      mitotic neurons.
AB  - The evolutionarily conserved Highwire (Hiw)/Drosophila Fsn E3 ubiquitin ligase
      complex is required for normal synaptic morphology during development and axonal
      regeneration after injury. However, little is known about the molecular
      mechanisms that regulate the Hiw E3 ligase complex. Using tandem affinity
      purification techniques, we identified Drosophila Rae1 as a previously unknown
      component of the Hiw/Fsn complex. Loss of Rae1 function in neurons results in
      morphological defects at the neuromuscular junction that are similar to those
      seen in hiw mutants. We found that Rae1 physically and genetically interacts with
      Hiw and restrains synaptic terminal growth by regulating the MAP kinase kinase
      kinase Wallenda. Moreover, we found that the Rae1 is both necessary and
      sufficient to promote Hiw protein abundance, and it does so by binding to Hiw and
      protecting Hiw from autophagy-mediated degradation. These results describe a
      previously unknown mechanism that selectively controls Hiw protein abundance
      during synaptic development.

PMID- 21874016
TI  - Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular
      glutamate transport.
AB  - The amount of neurotransmitter stored in a single synaptic vesicle can determine
      the size of the postsynaptic response, but the factors that regulate vesicle
      filling are poorly understood. A proton electrochemical gradient (DeltaMU(H+))
      generated by the vacuolar H(+)-ATPase drives the accumulation of classical
      transmitters into synaptic vesicles. The chemical component of DeltaMU(H+)
      (DeltapH) has received particular attention for its role in the vesicular
      transport of cationic transmitters as well as in protein sorting and degradation.
      Thus, considerable work has addressed the factors that promote DeltapH. However,
      synaptic vesicle uptake of the principal excitatory transmitter glutamate depends
      on the electrical component of DeltaMU(H+) (Deltapsi). We found that rat brain
      synaptic vesicles express monovalent cation/H(+) exchange activity that converts
      DeltapH into Deltapsi, and that this promotes synaptic vesicle filling with
      glutamate. Manipulating presynaptic K(+) at a glutamatergic synapse influenced
      quantal size, indicating that synaptic vesicle K(+)/H(+) exchange regulates
      glutamate release and synaptic transmission.

PMID- 21874017
TI  - A circadian clock in hippocampus is regulated by interaction between oligophrenin
      1 and Rev-erbalpha.
AB  - Oligophrenin-1 regulates dendritic spine morphology in the brain. Mutations in
      the oligophrenin-1 gene (OPHN1) cause intellectual disability. We discovered a
      previously unknown partner of oligophrenin-1, Rev-erbalpha, a nuclear receptor
      that represses the transcription of circadian oscillators. We found that
      oligophrenin-1 interacts with Rev-erbalpha in the mouse brain, causing it to
      locate to dendrites, reducing its repressor activity and protecting it from
      degradation. Our results indicate the presence of a circadian oscillator in the
      hippocampus, involving the clock gene Bmal1 (also known as Arntl), that is
      modulated by Rev-erbalpha and requires oligophrenin-1 for normal oscillation. We
      also found that synaptic activity induced Rev-erbalpha localization to dendrites
      and spines, a process that is mediated by AMPA receptor activation and requires
      oligophrenin-1. Our data reveal new interactions between synaptic activity and
      circadian oscillators, and delineate a new means of communication between nucleus
      and synapse that may provide insight into normal plasticity and the etiology of
      intellectual disability.

PMID- 21874018
TI  - lincRNAs act in the circuitry controlling pluripotency and differentiation.
AB  - Although thousands of large intergenic non-coding RNAs (lincRNAs) have been
      identified in mammals, few have been functionally characterized, leading to
      debate about their biological role. To address this, we performed loss-of
      function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells
      and characterized the effects on gene expression. Here we show that knockdown of
      lincRNAs has major consequences on gene expression patterns, comparable to
      knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect
      gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from
      the pluripotent state or upregulation of lineage commitment programs. We
      integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA
      genes are regulated by key transcription factors and that lincRNA transcripts
      bind to multiple chromatin regulatory proteins to affect shared gene expression
      programs. Together, the results demonstrate that lincRNAs have key roles in the
      circuitry controlling ES cell state.

PMID- 21874019
TI  - Structural basis of PIP2 activation of the classical inward rectifier K+ channel
      Kir2.2.
AB  - The regulation of ion channel activity by specific lipid molecules is widely
      recognized as an integral component of electrical signalling in cells. In
      particular, phosphatidylinositol 4,5-bisphosphate (PIP(2)), a minor yet dynamic
      phospholipid component of cell membranes, is known to regulate many different ion
      channels. PIP(2) is the primary agonist for classical inward rectifier (Kir2)
      channels, through which this lipid can regulate a cell's resting membrane
      potential. However, the molecular mechanism by which PIP(2) exerts its action is
      unknown. Here we present the X-ray crystal structure of a Kir2.2 channel in
      complex with a short-chain (dioctanoyl) derivative of PIP(2). We found that
      PIP(2) binds at an interface between the transmembrane domain (TMD) and the
      cytoplasmic domain (CTD). The PIP(2)-binding site consists of a conserved non
      specific phospholipid-binding region in the TMD and a specific
      phosphatidylinositol-binding region in the CTD. On PIP(2) binding, a flexible
      expansion linker contracts to a compact helical structure, the CTD translates 6 A
      and becomes tethered to the TMD and the inner helix gate begins to open. In
      contrast, the small anionic lipid dioctanoyl glycerol pyrophosphatidic acid (PPA)
      also binds to the non-specific TMD region, but not to the specific
      phosphatidylinositol region, and thus fails to engage the CTD or open the
      channel. Our results show how PIP(2) can control the resting membrane potential
      through a specific ion-channel-receptor-ligand interaction that brings about a
      large conformational change, analogous to neurotransmitter activation of ion
      channels at synapses.

PMID- 21874020
TI  - In vitro centromere and kinetochore assembly on defined chromatin templates.
AB  - During cell division, chromosomes are segregated to nascent daughter cells by
      attaching to the microtubules of the mitotic spindle through the kinetochore.
      Kinetochores are assembled on a specialized chromatin domain called the
      centromere, which is characterized by the replacement of nucleosomal histone H3
      with the histone H3 variant centromere protein A (CENP-A). CENP-A is essential
      for centromere and kinetochore formation in all eukaryotes but it is unknown how
      CENP-A chromatin directs centromere and kinetochore assembly. Here we generate
      synthetic CENP-A chromatin that recapitulates essential steps of centromere and
      kinetochore assembly in vitro. We show that reconstituted CENP-A chromatin when
      added to cell-free extracts is sufficient for the assembly of centromere and
      kinetochore proteins, microtubule binding and stabilization, and mitotic
      checkpoint function. Using chromatin assembled from histone H3/CENP-A chimaeras,
      we demonstrate that the conserved carboxy terminus of CENP-A is necessary and
      sufficient for centromere and kinetochore protein recruitment and function but
      that the CENP-A targeting domain--required for new CENP-A histone assembly--is
      not. These data show that two of the primary requirements for accurate chromosome
      segregation, the assembly of the kinetochore and the propagation of CENP-A
      chromatin, are specified by different elements in the CENP-A histone. Our unique
      cell-free system enables complete control and manipulation of the chromatin
      substrate and thus presents a powerful tool to study centromere and kinetochore
      assembly.

PMID- 21874021
TI  - Innate immune recognition of bacterial ligands by NAIPs determines inflammasome
      specificity.
AB  - Inflammasomes are a family of cytosolic multiprotein complexes that initiate
      innate immune responses to pathogenic microbes by activating the caspase 1
      protease. Although genetic data support a critical role for inflammasomes in
      immune defence and inflammatory diseases, the molecular basis by which individual
      inflammasomes respond to specific stimuli remains poorly understood. The
      inflammasome that contains the NLRC4 (NLR family, CARD domain containing 4)
      protein was previously shown to be activated in response to two distinct
      bacterial proteins, flagellin and PrgJ, a conserved component of pathogen
      associated type III secretion systems. However, direct binding between NLRC4 and
      flagellin or PrgJ has never been demonstrated. A homologue of NLRC4, NAIP5 (NLR
      family, apoptosis inhibitory protein 5), has been implicated in activation of
      NLRC4 (refs 7-11), but is widely assumed to have only an auxiliary role, as NAIP5
      is often dispensable for NLRC4 activation. However, Naip5 is a member of a small
      multigene family, raising the possibility of redundancy and functional
      specialization among Naip genes. Here we show in mice that different NAIP
      paralogues determine the specificity of the NLRC4 inflammasome for distinct
      bacterial ligands. In particular, we found that activation of endogenous NLRC4 by
      bacterial PrgJ requires NAIP2, a previously uncharacterized member of the NAIP
      gene family, whereas NAIP5 and NAIP6 activate NLRC4 specifically in response to
      bacterial flagellin. We dissected the biochemical mechanism underlying the
      requirement for NAIP proteins by use of a reconstituted NLRC4 inflammasome
      system. We found that NAIP proteins control ligand-dependent oligomerization of
      NLRC4 and that the NAIP2-NLRC4 complex physically associates with PrgJ but not
      flagellin, whereas NAIP5-NLRC4 associates with flagellin but not PrgJ. Our
      results identify NAIPs as immune sensor proteins and provide biochemical evidence
      for a simple receptor-ligand model for activation of the NAIP-NLRC4
      inflammasomes.

PMID- 21874022
TI  - Multiple reference genomes and transcriptomes for Arabidopsis thaliana.
AB  - Genetic differences between Arabidopsis thaliana accessions underlie the plant's
      extensive phenotypic variation, and until now these have been interpreted largely
      in the context of the annotated reference accession Col-0. Here we report the
      sequencing, assembly and annotation of the genomes of 18 natural A. thaliana
      accessions, and their transcriptomes. When assessed on the basis of the reference
      annotation, one-third of protein-coding genes are predicted to be disrupted in at
      least one accession. However, re-annotation of each genome revealed that
      alternative gene models often restore coding potential. Gene expression in
      seedlings differed for nearly half of expressed genes and was frequently
      associated with cis variants within 5 kilobases, as were intron retention
      alternative splicing events. Sequence and expression variation is most pronounced
      in genes that respond to the biotic environment. Our data further promote
      evolutionary and functional studies in A. thaliana, especially the MAGIC genetic
      reference population descended from these accessions.

PMID- 21874023
TI  - The antiviral factor APOBEC3G enhances the recognition of HIV-infected primary T
      cells by natural killer cells.
AB  - APOBEC3G (A3G) is an intrinsic antiviral factor that inhibits the replication of
      human immunodeficiency virus (HIV) by deaminating cytidine residues to uridine.
      This causes guanosine-to-adenosine hypermutation in the opposite strand and
      results in inactivation of the virus. HIV counteracts A3G through the activity of
      viral infectivity factor (Vif), which promotes degradation of A3G. We report that
      viral protein R (Vpr), which interacts with a uracil glycosylase, also
      counteracted A3G by diminishing the incorporation of uridine. However, this
      process resulted in activation of the DNA-damage-response pathway and the
      expression of natural killer (NK) cell-activating ligands. Our results show that
      pathogen-induced deamination of cytidine and the DNA-damage response to virus
      mediated repair of the incorporation of uridine enhance the recognition of HIV
      infected cells by NK cells.

PMID- 21874027
TI  - The body adiposity index and the sexual dimorphism in body fat.

PMID- 21874024
TI  - The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents
      autoimmunity.
AB  - T cell activation is subject to tight regulation to avoid inappropriate responses
      to self antigens. Here we show that genetic deficiency in the ubiquitin ligase
      Peli1 caused hyperactivation of T cells and rendered T cells refractory to
      suppression by regulatory T cells and transforming growth factor-beta (TGF-beta).
      As a result, Peli1-deficient mice spontaneously developed autoimmunity
      characterized by multiorgan inflammation and autoantibody production. Peli1
      deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF
      kappaB family of transcription factors with pivotal roles in T cell activation.
      Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our
      results identify Peli1 as a critical factor in the maintenance of peripheral T
      cell tolerance and demonstrate a previously unknown mechanism of c-Rel
      regulation.

PMID- 21874025
TI  - IL-22 bridges the lymphotoxin pathway with the maintenance of colonic lymphoid
      structures during infection with Citrobacter rodentium.
AB  - Colonic patches (CLPs) and isolated lymphoid follicles (ILFs) are two main
      lymphoid structures in the colon. Lymphoid tissue-inducer cells (LTi cells) are
      indispensable for the development of ILFs. LTi cells also produce interleukin 17
      (IL-17) and IL-22, signature cytokines secreted by IL-17-producing helper T
      cells. Here we report that IL-22 acted downstream of the lymphotoxin pathway and
      regulated the organization and maintenance of mature CLPs and ILFs in the colon
      during infection with Citrobacter rodentium. Lymphotoxin (LTalpha(1)beta(2))
      regulated the production of IL-22 during infection with C. rodentium, but the
      lymphotoxin-like protein LIGHT did not. IL-22 signaling was sufficient to restore
      the organization of CLPs and ILFs and host defense against infection with C.
      rodentium in mice lacking lymphotoxin signals, which suggests that IL-22 connects
      the lymphotoxin pathway to mucosal epithelial defense mechanisms.

PMID- 21874028
TI  - Response to "Weight loss, blood pressure reduction, and aortic stiffness: an old
      dilemma revisited".

PMID- 21874029
TI  - Low DHEAS levels are associated with depressive symptoms in elderly Chinese men:
      results from a large study.
AB  - This study investigated the association between depressive symptoms in elderly
      Chinese men and the total testosterone, dehydroepiandrosterone (DHEA), DHEA
      sulphate (DHEAS), oestradiol and sex hormone-binding globulin (SHBG) levels, and
      the free androgen index. Cross-sectional data from 1147 community-dwelling
      elderly men, aged 65 and older, were used. Depressive symptoms were measured
      using the Chinese Geriatric Depression Scale (GDS). Total testosterone, free
      testosterone, DHEA, DHEAS, total oestradiol, the free androgen index and SHBG
      levels were assessed. DHEA was significantly associated with GDS score, and there
      was a trend towards DHEAS association, but this was not significant (beta=-0.110,
      P=0.015; beta=-0.074, P=0.055). However, no association was seen between
      depressive symptoms and total testosterone levels, free testosterone levels,
      oestradiol levels or SHBG levels. In terms of the presence of clinically relevant
      depressive symptoms, there were no statistically significant differences between
      patients in the lowest quartile of sex steroid hormone levels and those in other
      quartiles of sex steroid hormone levels. Similarly to Western studies, our study
      shows that DHEA and DHEAS levels are associated with depressive symptoms.

PMID- 21874030
TI  - Increased expression of insulin-like growth factor-binding protein-3 is
      implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after
      propranolol treatment.
AB  - This study aimed to investigate the role of insulin-like growth factor-binding
      protein-3 (IGFBP-3) in erectile dysfunction (ED) in two-kidney one-clip (2K-1C)
      hypertensive rats treated with the beta-blocking agent propranolol. Adult male
      Wistar rats were randomly divided into three groups: a normal control group, a
      hypertensive control group and a propranolol treatment group (n=9). After 4 weeks
      of propranolol treatment, intracavernous pressure (ICP) responses to electrical
      stimulation of the cavernous nerves were evaluated. The expression of IGFBP-3 and
      insulin-like growth factor-1 (IGF-1) mRNA and protein in the rat cavernous tissue
      were detected by quantitative real-time PCR and Western blot, respectively. The
      concentration of cyclic guanosine monophosphate (cGMP) in the cavernous tissue
      was determined by enzyme-linked immunosorbent assay (ELISA). Cavernosal pressure
      in response to cavernous nerve stimulation was decreased 4 weeks after
      propranolol treatment (P<0.01, compared to the hypertensive control group). IGFBP
      3 mRNA and protein expression was increased in the propranolol treatment group
      compared to the hypertensive control group (P<0.01), whereas IGF-1 expression was
      decreased in the propranolol treatment group compared to the hypertensive control
      group (P<0.01). In addition, cavernous cGMP concentration was decreased in the
      propranolol treatment group compared to the hypertensive control group (P<0.01).
      Taken together, these results suggest that the upregulation of IGFBP-3 may play a
      role in the development of ED in hypertensive rats.

PMID- 21874031
TI  - Learning to think continentally.
AB  - The US Department of Health and Human Services (DHHS) is proposing to enhance
      federal regulation intended to protect human research subjects, in particular to
      increase measures aimed at security of personal data. Since the ethical review
      process is partially based on respect for people and their autonomy,
      harmonization of these rules will be a process of convincing individuals and
      their states to accept uniform standards that give enough privacy but do not lock
      away personal data from either research participants or researchers.

PMID- 21874032
TI  - Admixture provides new insights into recombination.

PMID- 21874033
TI  - Lyp breakdown and autoimmunity.

PMID- 21874034
TI  - A20 edits ubiquitin and autoimmune paradigms.

PMID- 21874042
TI  - Polymorphisms in miRNA binding site: new insight into small cell lung cancer
      susceptibility.

PMID- 21874043
TI  - Neutrophils, reverse traffic and detrimental potential.

PMID- 21874044
TI  - Regulation of APC/CCdc20 activity by RASSF1A-APC/CCdc20 circuitry.
AB  - RASSF1A is a key tumor-suppressor gene that is often inactivated in a wide
      variety of solid tumors. Studies have illustrated that RASSF1A plays vital roles
      in the regulation of cell-cycle progression and functions as a guardian of
      mitosis. Nevertheless, the precise mechanism of RASSF1A-dependent regulation of
      mitosis remains largely unclear. APC/C(Cdc20) is the master switch and regulator
      of mitosis. The activity of APC/C(Cdc20) is tightly controlled by phosphorylation
      and specific inhibitors to ensure the sequential ubiquitination of downstream
      targets. Here, we report on the novel finding of a regulated circuitry that
      controls the timely expression and hence activity of APC/C(Cdc20) during mitosis.
      Our study showed that RASSF1A and APC/C(Cdc20) form a molecular relay that
      regulates the APC/C(Cdc20) activity at early mitosis. We found that RASSF1A
      inhibits APC/C(Cdc20) function through its D-box motifs. Paradoxically, RASSF1A
      was also demonstrated to be ubiquitinated by APC/C(Cdc20) in vitro and degraded
      at prometaphase despite of active spindle checkpoint presence. The first two
      unique D-boxes at the N-terminal of RASSF1A served as specific degron recognized
      by APC/C(Cdc20). Importantly, we found that Aurora A and Aurora B directly
      phosphorylate RASSF1A, a critical step by which RASSF1A switches from being an
      inhibitor to a substrate of APC/C(Cdc20) during the course of mitotic
      progression. As a result of RASSF1A degradation, APC/C(Cdc20) can then partially
      activate the ubiquitination of Cyclin A in the presence of spindle checkpoint.
      This circuitry is essential for the timely degradation of Cyclin A. To conclude,
      our results propose a new model for RASSF1A-APC/C(Cdc20) interaction in ensuring
      the sequential progression of mitosis.

PMID- 21874046
TI  - MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing
      SMAD4 in thyroid cancer.
AB  - MicroRNAs (miRNA) are small non-coding RNAs involved in post-transcriptional gene
      regulation that have crucial roles in several types of tumors, including
      papillary thyroid carcinoma (PTC). miR-146b-5p is overexpressed in PTCs and is
      regarded as a relevant diagnostic marker for this type of cancer. A computational
      search revealed that miR-146b-5p putatively binds to the 3' untranslated region
      (UTR) of SMAD4, an important member of the transforming growth factor beta (TGF
      beta) signaling pathway. The TGF-beta pathway is a negative regulator of thyroid
      follicular cell growth, and the mechanism by which thyroid cancer cells evade its
      inhibitory signal remains unclear. We questioned whether the modulation of the
      TGF-beta pathway by miR-146b-5p can contribute to thyroid tumorigenesis.
      Luciferase reporter assay confirmed the direct binding of miR-146b-5p on the
      SMAD4 3'UTR. Specific inhibition of miR-146b-5p with a locked nucleic acid
      modified anti-miR-146b oligonucleotide significantly increased SMAD4 levels in
      the human papillary carcinoma cell lines, TPC-1 and BCPAP. Moreover, suppression
      of miR-146b-5p increased the cellular response to the TGF-beta anti-proliferative
      signal, significantly decreasing the proliferation rate. The overexpression of
      miR-146b-5p in normal rat follicular PCCL3 cells decreased SMAD4 levels and
      disrupted TGF-beta signal transduction. MiR-146b-5p overexpression in PCCL3 cells
      also significantly increased cell proliferation in the absence of thyroid
      stimulating hormone and conferred resistance to TGF-beta-mediated cell-cycle
      arrest. Additionally, the activation of thyroid most common oncogenes RET/PTC3
      and BRAF in PCCL3 cells upregulated miR-146b-5p expression. Our results confirm
      the oncogenic role of miR-146b-5p in thyroid follicular cells and contribute to
      knowledge regarding the modulation of TGF-beta signal transduction by miRNAs in
      PTCs.

PMID- 21874045
TI  - Oncogenic YAP promotes radioresistance and genomic instability in medulloblastoma
      through IGF2-mediated Akt activation.
AB  - Radiation therapy remains the standard of care for many cancers, including the
      malignant pediatric brain tumor medulloblastoma. Radiation leads to long-term
      side effects, whereas radioresistance contributes to tumor recurrence. Radio
      resistant medulloblastoma cells occupy the perivascular niche. They express Yes
      associated protein (YAP), a Sonic hedgehog (Shh) target markedly elevated in Shh
      driven medulloblastomas. Here we report that YAP accelerates tumor growth and
      confers radioresistance, promoting ongoing proliferation after radiation. YAP
      activity enables cells to enter mitosis with un-repaired DNA through driving
      insulin-like growth factor 2 (IGF2) expression and Akt activation, resulting in
      ATM/Chk2 inactivation and abrogation of cell cycle checkpoints. Our results
      establish a central role for YAP in counteracting radiation-based therapies and
      driving genomic instability, and indicate the YAP/IGF2/Akt axis as a therapeutic
      target in medulloblastoma.

PMID- 21874048
TI  - Stabilization of phenotypic plasticity through mesenchymal-specific DNA
      hypermethylation in cancer cells.
AB  - The epithelial-mesenchymal transition (EMT) has a crucial role in normal and
      disease processes including tumor progression. In this study, we first classified
      epithelial-like and mesenchymal-like oral squamous cell carcinoma (OSCC) cell
      lines based on expression profiles of typical EMT-related genes using a panel of
      18 OSCC cell lines. Then, we performed methylation-based and expression-based
      analyses of components of the Wnt signaling pathway, and identified WNT7A and
      WNT10A as genes silenced by mesenchymal-specific DNA hypermethylation in OSCCs. A
      significant association was revealed between some clinicopathological findings
      and the DNA methylation status of WNT7A (normal vs tumor, P=0.007; T1-2 vs T3-4,
      P=0.040; I-III vs IV, P=0.016) and WNT10A (N0-N1 vs N2-N3, P=0.046) in the
      advanced stages of OSCC. Moreover, we found that E-cadherin expression in cancer
      cells may be positively regulated by WNT7A, whose expression is negatively
      regulated by mesenchymal-specific DNA hypermethylation or ZEB1 in mesenchymal
      like OSCC cells. Our findings indicate that epithelial-specific gene silencing
      through mesenchymal-specific DNA hypermethylation may stabilize the phenotypic
      plasticity of cancer cells during EMT/MET.

PMID- 21874049
TI  - Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and
      mesenchymal transitions in human tumorigenesis.
AB  - Epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions occur
      in the development of human tumorigenesis and are part of the natural history of
      the process to adapt to the changing microenvironment. In this setting, the miR
      200 family is recognized as a master regulator of the epithelial phenotype by
      targeting ZEB1 and ZEB2, two important transcriptional repressors of the cell
      adherence (E-cadherin) and polarity (CRB3 and LGL2) genes. Recently, the putative
      DNA methylation associated inactivation of various miR-200 members has been
      described in cancer. Herein, we show that the miR-200ba429 and miR-200c141
      transcripts undergo a dynamic epigenetic regulation linked to EMT or MET
      phenotypes in tumor progression. The 5'-CpG islands of both miR-200 loci were
      found unmethylated and coupled to the expression of the corresponding miRNAs in
      human cancer cell lines with epithelial features, such as low levels of ZEB1/ZEB2
      and high expression of E-cadherin, CRB3 and LGL2, while CpG island
      hypermethylation-associated silencing was observed in transformed cells with
      mesenchymal characteristics. The recovery of miR-200ba429 and miR-200c141
      expression by stable transfection in the hypermethylated cells restored the
      epithelial markers and inhibited migration in cell culture and tumoral growth and
      metastasis formation in nude mice. We also discovered, using both cell culture
      and animal models, that the miR-200 epigenetic silencing is not an static and
      fixed process but it can be shifted to hypermethylated or unmethylated 5'-CpG
      island status corresponding to the EMT and MET phenotypes, respectively. In fact,
      careful laser microdissection in human primary colorectal tumorigenesis unveiled
      that in normal colon mucosa crypts (epithelia) and stroma (mesenchyma) already
      are unmethylated and methylated at these loci, respectively; and that the
      colorectal tumors undergo selective miR-200 hypermethylation of their epithelial
      component. These findings indicate that the epigenetic silencing plasticity of
      the miR-200 family contributes to the evolving and adapting phenotypes of human
      tumors.

PMID- 21874050
TI  - A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to
      regulate accumulation of Fra-1 in tumour cells.
AB  - Fos-related antigen-1 (Fra-1) is a member of the Activator Protein-1 (AP-1)
      transcription factor superfamily that is overexpressed in a variety of cancers,
      including colon, breast, lung, bladder and brain. High Fra-1 levels are
      associated with enhanced cell proliferation, survival, migration and invasion.
      Despite its frequent overexpression, the molecular mechanisms that regulate the
      accumulation of Fra-1 proteins in tumour cells are not well understood. Here, we
      show that turnover of Fra-1, which does not require ubiquitylation, is
      cooperatively regulated by two distinct mechanisms-association with the 19S
      proteasomal subunit, TBP-1, and by a C-terminal degron, which acts independently
      of TBP-1, but is regulated by RAS-ERK (extracellular signal-regulated kinase)
      signalling. TBP-1 depletion stabilized Fra-1 and further increased its levels in
      tumour cells expressing RAS-ERK pathway oncogenes. These effects correlated with
      increased AP-1 transcriptional activity. We suggest that during Fra-1
      degradation, association with TBP-1 provides a mechanism for ubiquitin
      independent proteasomal recognition, while the C terminus of the protein
      regulates its subsequent proteolytic processing.

PMID- 21874052
TI  - Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells
      with stem cell properties.
AB  - Emerging evidence suggests that cancers arise in stem/progenitor cells. Yet, the
      requirements for transformation of these primitive cells remains poorly
      understood. In this study, we have exploited the 'mammosphere' system that
      selects for primitive mammary stem/progenitor cells to explore their potential
      and requirements for transformation. Introduction of Simian Virus 40 Early Region
      and hTERT into mammosphere-derived cells led to the generation of NBLE, an
      immortalized mammary epithelial cell line. The NBLEs largely comprised of bi
      potent progenitors with long-term self-renewal and multi-lineage differentiation
      potential. Clonal and karyotype analyses revealed the existence of heterogeneous
      population within NBLEs with varied proliferation, differentiation and sphere
      forming potential. Significantly, injection of NBLEs into immunocompromised mice
      resulted in the generation of invasive ductal adenocarcinomas. Further, these
      cells harbored a sub-population of CD44(+)/CD24(-) fraction that alone had sphere
      and tumor-initiating potential and resembled the breast cancer stem cell gene
      signature. Interestingly, prolonged in vitro culturing led to their further
      enrichment. The NBLE cells also showed increased expression of stemness and
      epithelial to mesenchymal transition markers, deregulated self-renewal pathways,
      activated DNA-damage response and cancer-associated chromosomal aberrations-all
      of which are likely to have contributed to their tumorigenic transformation.
      Thus, unlike previous in vitro transformation studies that used adherent, more
      differentiated human mammary epithelial cells our study demonstrates that the
      mammosphere-derived, less-differentiated cells undergo tumorigenic conversion
      with only two genetic elements, without requiring oncogenic Ras. Moreover, the
      striking phenotypic and molecular resemblance of the NBLE-generated tumors with
      naturally arising breast adenocarcinomas supports the notion of a primitive
      breast cell as the origin for this subtype of breast cancer. Finally, the NBLEs
      represent a heterogeneous population of cells with striking plasticity, capable
      of differentiation, self-renewal and tumorigenicity, thus offering a unique model
      system to study the molecular mechanisms involved with these processes.

PMID- 21874051
TI  - Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.
AB  - MicroRNAs (miRNAs) carry out post-transcriptional control of a multitude of
      cellular processes. Aberrant expression of miRNA can lead to diseases, including
      cancer. Gliomas are aggressive brain tumors that are thought to arise from
      transformed glioma-initiating neural stem cells (giNSCs). With the use of giNSCs
      and human glioblastoma cells, we investigated the function of miRNAs in gliomas.
      We identified pro-neuronal miR-128 as a candidate glioma tumor suppressor miRNA.
      Decreased expression of miR-128 correlates with aggressive human glioma subtypes.
      With a combination of molecular, cellular and in vivo approaches, we characterize
      miR-128's tumor suppressive role. miR-128 represses giNSC growth by enhancing
      neuronal differentiation. miR-128 represses growth and mediates differentiation
      by targeting oncogenic receptor tyrosine kinases (RTKs) epithelial growth factor
      receptor and platelet-derived growth factor receptor-alpha. Using an
      autochthonous glioma mouse model, we demonstrated that miR-128 repressed
      gliomagenesis. We identified miR-128 as a glioma tumor suppressor that targets
      RTK signaling to repress giNSC self-renewal and enhance differentiation.

PMID- 21874053
TI  - Integrating developmental signals: a Hippo in the (path)way.
AB  - The Hippo pathway, a signaling cascade that controls cell cycle progression,
      apoptosis and cell differentiation, has emerged as a fundamental regulator of
      many physiological and pathological processes. Recent studies have revealed a
      complex network of interactions directing Hippo pathway activity, and have
      connected this pathway with other key signaling pathways. Such crosstalk has
      uncovered novel roles for Hippo signaling, including regulation of TGFbeta/SMAD
      and WNT/beta-catenin pathways. This review highlights some of the recent findings
      in the Hippo field with an emphasis on how the Hippo pathway is integrated with
      other pathways to mediate diverse processes.

PMID- 21874054
TI  - The impact of hematopoietic stem cell transplantation on sexuality: a systematic
      review of the literature.
AB  - In this paper we review evidence concerning the impact of hematopoietic SCT
      (HSCT) on sexuality. The aims are to determine: (1) the sexual changes
      experienced by patients following allogeneic or autologous HSCT, and its
      consequences; (2) changes in the sexual function over time and (3) the impact of
      physiological changes induced by intensive treatment with radiation and
      chemotherapy on sexual functioning. Four databases were searched for articles
      published between January 1995 and May 2011. A total of 14 studies were
      identified and analyzed. We found that (1) multiple aspects of sexuality were
      affected, and the impact and etiology of these sexual alterations were different
      between genders, and (2) recovery of sexual activity and pleasure occurred in the
      first 2 years after HSCT, although it appears that some survivors are more likely
      to experience sexual dysfunction even 5-10 years after HSCT as compared with
      controls; and (3) there was contradictory evidence concerning possible
      differences between allogeneic and autologous HSCT, although there was a
      significant relation between the sexual dysfunctions and the type of chemotherapy
      administrated as conditioning and chronic GVHD. Future prospective research in
      sexual dysfunction with specific reliable validated instruments and more adequate
      sample sizes will be required to definitively evaluate the impact of HSCT on
      sexuality.

PMID- 21874055
TI  - Intravenous compared with oral busulfan as preparation for allogeneic
      hematopoietic progenitor cell transplantation for AML and MDS.
AB  - BU and CY is a common conditioning regimen for allogeneic hematopoietic
      progenitor cell transplantation (HPCT). I.v. BU is increasingly used in place of
      the oral formulation for conditioning. We compared the outcomes of 135
      consecutively treated AML and myelodysplastic syndrome patients who underwent
      allogeneic HPCT at our institution with BUCY2 using oral (n=93) or i.v. (n=42)
      BU, without dose adjustment. The i.v. BU patients had a lower incidence of any
      severity of oral mucositis (3 versus 55%, P=0.002) and severe mucositis (3 versus
      24%, P=0.005). Other post transplant outcomes were comparable between the groups.
      In all 26 i.v. BU and 33 oral BU patients are alive; however, the median follow
      up was significantly longer for the oral BU group. One- and two-year non-relapse
      mortality for the i.v. BU patients was 21% for both, and for the oral BU group
      was 23% and 29%, respectively. One- and two-year relapse mortality for the i.v.
      BU patients was 21% for both, and for the oral BU group was 24% and 29%,
      respectively. Substituting i.v. for oral BU reduces variability in drug exposure
      and potentially improves toxicity as suggested by our finding of significantly
      less oral mucositis and decreased severity with i.v. BU.

PMID- 21874056
TI  - Haematological malignancies in sibling and unrelated donors of allogeneic
      peripheral stem cells mobilised with G-CSF filgrastim: a transplant centre and
      Czech National Marrow Donors Registry experience.

PMID- 21874057
TI  - Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options.
AB  - Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a
      serious complication affecting 1.7-26% of the patients, with a reported mortality
      rate of 21-100%. It is considered a manifestation of chronic graft-versus-host
      disease, but our knowledge of aetiology and pathogenesis is still limited.
      Diagnostic criteria are being developed, and will allow more uniform and
      comparable research activities between centres. At present, no randomised
      controlled trials have been completed that could demonstrate an effective
      treatment. Steroids in combination with other immunosuppressive drugs still
      constitute the backbone of the treatment strategy, and results from our and other
      centres suggest that monthly infusions of high-dose pulse i.v. methylprednisolone
      (HDPM) might stabilise the disease and hinder progression. This article provides
      an overview of the current evidence regarding treatment options for BO and
      presents the treatment results with HDPM in a paediatric national HSCT-cohort.

PMID- 21874058
TI  - Successful treatment of isohemagglutinin-mediated pure red cell aplasia after ABO
      mismatched allogeneic hematopoietic cell transplant using bortezomib.

PMID- 21874059
TI  - The effect of oral management on the severity of oral mucositis during
      hematopoietic SCT.
AB  - Oral mucositis (OM) is a frequent adverse effect of allogenic or autologous
      hematopoietic SCT. It results from direct toxic injury to the mucosal epithelial
      cells by the immunosuppressive regimen. Here, we compared the incidence and
      severity of OM between a group of 24 patients who received proper oral management
      during hematopoietic SCT and a group of 24 who did not. The oral management group
      received pre-hematopoietic SCT instruction on oral care and an oral examination
      in the clean room. Differences in the incidence and severity of OM between the
      two groups were examined statistically. OM was observed in 14 (58.3%) patients in
      the oral management group and 22 (91.6%) in the control group. The median of the
      OM score was 1 for the oral management group (range 0 to 3) and 2 for the control
      group (range 0 to 3). There was a significant difference in the OM score (P<0.05)
      and in the incidence of OM between the two groups (P<0.01). This study shows that
      oral management may decrease the occurrence of OM. Our results also suggest that
      it is important to include an oral management provider on the hematopoietic SCT
      team.

PMID- 21874060
TI  - Stem cell transplant for Waldenstrom macroglobulinemia: an underutilized
      technique.
AB  - Waldenstrom macroglobulinemia is a highly chemosensitive lymphoplasmacytic
      lymphoma with response rates of 90% to first-line chemotherapy. The fraction of
      patients undergoing stem cell transplant for this disorder appears to be lower
      than that of patients with multiple myeloma. The indolent nature and favorable
      genetic profile should make Waldenstrom an ideal disorder for autologous stem
      cell transplant, with high response rates that are durable. We review the
      literature on autologous and allogeneic transplants for Waldenstrom
      macroglobulinemia and conclude that autologous transplant is effective and
      underutilized in the management of this disorder. Allogeneic transplant should be
      considered investigational and used only in the context of a clinical trial or
      when other chemotherapeutic options have been exhausted.

PMID- 21874062
TI  - Infusion of autologous peripheral blood stem cells in an unrelated donor who
      developed severe aplastic anemia following stem cell donation.

PMID- 21874061
TI  - Ustekinumab demonstrates activity in glucocorticoid-refractory acute GVHD.

PMID- 21874063
TI  - Increased costs after allogeneic haematopoietic SCT are associated with major
      complications and re-transplantation.
AB  - We wanted to evaluate factors associated with high costs after allogeneic
      haematopoietic SCT (HSCT). We collected all in-patient and outpatient costs
      during the first year after HSCT over 5 years, from 2003 to 2007. Mean 1-year
      costs per patient were ?[euro]141,493 (95% confidence interval (95% CI)=125,019
      157,967). Patients treated with non-myeloablative conditioning (NMC) had reduced
      costs, but patients treated with reduced-intensity or myeloablative conditioning
      had similar 1-year costs. Multivariate analysis showed that increased 1-year
      costs were seen in post-transplant complications: rejection (relative hazard (RH)
      1.24, P<0.001), acute GVHD of grades III-IV (1.31, P<0.001) and invasive fungal
      infection (1.15, P=0.02). In addition, increased costs were associated with re
      transplantation (1.21, P=0.001), mesenchymal stem-cell therapy (1.26, P<0.001),
      unrelated donor transplants (1.20, P=0.002) and the need for G-CSF treatment due
      to poor engraftment (1.12, P=0.047). In patients without any of these risk
      factors, mean 1-year costs were ?[euro]84,773 (95% CI=71,145-98,400) (n=51). With
      three risk factors, the cost increased to ?[euro]249,775 (95% CI=166,824-332,727)
      (n=14). To conclude, major complications increased the costs of HSCT. Unrelated
      donor transplants were more expensive than HLA-identical sibling transplants.
      Costs were reduced in patients treated with NMC.

PMID- 21874064
TI  - Novel agents and approaches for stem cell mobilization in normal donors and
      patients.
AB  - In spite of the safety and efficiency of the classical mobilization protocols,
      recombinant human G-CSF+/-chemotherapy, there is still a considerable amount of
      mobilization failures (10-30%), which warrant novel agents and approaches both in
      an autologous and an allogeneic transplant setting. Attempts to improve CD34+
      yields by using several cytokines and growth factors as adjuncts to G-CSF could
      not change the standard approaches during the last decade, either because of
      inefficiency or the adverse events encountered with these agents. As a long
      acting G-CSF analog, pegfilgrastim has the advantages of an earlier start of
      apheresis, reduction in the number of apheresis procedures as well as a reduced
      number of injections as compared with unconjugated G-CSF. However, dosing and
      cost-effectiveness especially in cytokine-only mobilizations require further
      investigation. As interactions between hematopoietic stem cells and the BM
      microenvironment are better understood, new molecules targeting these
      interactions are emerging. Plerixafor, which started its journey as an anti-HIV
      drug, recently ended up being a popular stem cell mobilizer with the ability of
      rapid mobilization and gained approval as an adjunct to G-CSF for poor
      mobilizers. At present, it is challenging to search for the best approach by
      using the available drugs with appropriate timing to provide sufficient CD34+
      yield after an initial mobilization attempt, and in a cost-effective manner
      thereby avoiding further mobilization attempts and exposure to chemotherapy.
      Approaches not only for increasing stem cell yield, but also aiming to improve
      the quality of graft content and the associated transplantation outcomes are
      promising areas of research.

PMID- 21874066
TI  - Global Patterns and Determinants of Sex Differences in Smoking.
AB  - The worldwide spread of tobacco use in recent decades raises questions about the
      relative prevalence of smoking among men and women. Does the degree of gender
      equality in nations promote equality in cigarette use? Does rising use of
      cigarettes by women stem from the stage of cigarette diffusion and earlier
      increases among men? Or have changes in economic factors and smoking policy
      affected the sexes differently? This study uses aggregate data for 106 nations,
      measures of smoking prevalence circa 2000, and lagged measures of gender
      equality, cigarette diffusion, and tobacco access to address these questions and
      evaluate the underlying theories. With the logged ratio of female to male
      prevalence as the dependent variable, regression results reveal that gender
      equality has inconsistent effects on women's smoking relative to men, cigarette
      diffusion has more consistent and moderately strong effects, and economic factors
      have weak effects. Global patterns of adoption of cigarettes by women appear most
      closely associated with the early adoption by men and then movement through a
      regular pattern of cigarette diffusion.

PMID- 21874067
TI  - I only have eyes for you: Ovulation redirects attention (but not memory) to
      attractive men.
AB  - A number of studies have found a disjunction between women's attention to, and
      memory for, handsome men. Although women pay initial attention to handsome men,
      they do not remember those men later. The present study examines how ovulation
      might differentially affect these attentional and memory processes. We found that
      women near ovulation increased their visual attention to attractive men. However,
      this increased visual attention did not translate into better memory. Discussion
      focuses on possible explanations, in the context of an emerging body of findings
      on disjunctions between attention to, and memory for, other people.

PMID- 21874065
TI  - BIOMIMETIC GRADIENT HYDROGELS FOR TISSUE ENGINEERING.
AB  - During tissue morphogenesis and homeostasis, cells experience various signals in
      their environments, including gradients of physical and chemical cues. Spatial
      and temporal gradients regulate various cell behaviours such as proliferation,
      migration, and differentiation during development, inflammation, wound healing,
      and cancer. One of the goals of functional tissue engineering is to create
      microenvironments that mimic the cellular and tissue complexity found in vivo by
      incorporating physical, chemical, temporal, and spatial gradients within
      engineered three-dimensional (3D) scaffolds. Hydrogels are ideal materials for 3D
      tissue scaffolds that mimic the extracellular matrix (ECM). Various techniques
      from material science, microscale engineering, and microfluidics are used to
      synthesise biomimetic hydrogels with encapsulated cells and tailored
      microenvironments. In particular, a host of methods exist to incorporate
      micrometer to centimetre scale chemical and physical gradients within hydrogels
      to mimic the cellular cues found in vivo. In this review, we draw on specific
      biological examples to motivate hydrogel gradients as tools for studying cell
      material interactions. We provide a brief overview of techniques to generate
      gradient hydrogels and showcase their use to study particular cell behaviours in
      two-dimensional (2D) and 3D environments. We conclude by summarizing the current
      and future trends in gradient hydrogels and cell-material interactions in context
      with the long-term goals of tissue engineering.

PMID- 21874068
TI  - Long Run Returns to Education: Does Schooling Lead to an Extended Old Age?
AB  - While there is no doubt that health is strongly correlated with education,
      whether schooling exerts a causal impact on health is not firmly established. We
      exploit a Dutch compulsory schooling law to estimate the causal effect of
      education on mortality. The reform provides a powerful instrument, significantly
      raising years of schooling, which, in turn, has a significant and robust negative
      effect on mortality. For men surviving to age 81, an extra year of schooling is
      estimated to reduce the probability of dying before the age of 89 by almost 3
      percentage points relative to a baseline of 50 percent.

PMID- 21874069
TI  - The Longitudinal Influence of Coparenting Conflict on Parental Negativity and
      Adolescent Maladjustment.
AB  - This study addresses two limitations of coparenting research: first, little
      research on coparenting has been conducted with families of adolescents, and
      second, there is little understanding regarding the child and family contexts in
      which coparenting is most salient. The longitudinal relation of coparenting
      conflict to parenting and adolescent maladjustment across 3 years was
      investigated among 516 2-parent, 2-adolescent families. Coparenting conflict
      predicted as much or more unique variance in parenting and adolescent adjustment
      as did marital quality and disagreement together. After controlling for
      stability, coparenting conflict predicted mothers' and fathers' negativity and
      adolescent antisocial behavior (but not depression). Importantly, the influence
      of coparenting conflict in all cases varied as a function of family type,
      adolescent gender, or initial level of antisocial behavior, or all. The
      implications of these results for family processes in different relational and
      developmental contexts are discussed.

PMID- 21874070
TI  - The Association Between Natural Amenities, Rural Population Growth, and Long-Term
      Residents' Economic Well-Being.
AB  - Population growth in rural areas characterized by high levels of natural
      amenities has recently received substantial research attention. A noted concern
      with amenity-driven rural population growth is its potential to raise local costs
      of-living while yielding only low-wage service sector employment for long-term
      residents. The work presented here empirically models long-term rural residents'
      economic well-being, making use of longitudinal data from the Panel Study of
      Income Dynamics. In general, the results suggest that long-term rural families
      residing in high-growth amenity and recreation areas tend to have higher annual
      incomes than do their counterparts in non-growth amenity/recreation areas,
      regardless of the sex, race, or age of the family head. However, higher costs-of
      living in these areas supplant any relative gains in income. As such, these
      analyses provide empirical evidence of patterns inferred by earlier anecdotal
      evidence and case studies.

PMID- 21874071
TI  - Environmental Racial Inequality in Detroit.
AB  - This study uses industrial pollution data from the Environmental Protection
      Agency's Toxics Release Inventory (TRI) and tract-level demographic data from the
      2000 U.S. census to determine whether environmental racial inequality existed in
      the Detroit metropolitan area in the year 2000. This study differs from prior
      environmental inequality research in two important ways. First, it offers a
      positive rationale for using hazard proximity indicators. Second, it uses a
      distance decay modeling technique to estimate hazard proximity. This technique
      weights each hazard's estimated negative effect by distance such that the
      estimated negative effect declines continuously as distance from the hazard
      increases, thus providing more accurate estimates of proximity-based
      environmental risk than can be obtained using other variable construction
      techniques currently found in the literature. Using this technique, I find that
      Detroit's black neighborhoods were disproportionately burdened by TRI facility
      activity in 2000 and that neighborhood racial composition had a strong
      independent effect on neighborhood proximity to TRI activity.

PMID- 21874072
TI  - National Income, Inequality and Global Patterns of Cigarette Use.
AB  - Declining tobacco use in high-income nations and rising tobacco use in low- and
      middle-income nations raises questions about the sources of worldwide patterns of
      smoking. Theories posit a curvilinear influence of national income based on the
      balance of affordability and health-cost effects. In addition, however, economic
      inequality, gender inequality and government policies may moderate the rise and
      fall in smoking prevalence with national income. This study tests these arguments
      using aggregate data for 145 nations and measures of smoking prevalence circa
      2000. The results show nonlinear effects of national income for males that take
      the form of an inverted U, but show linear effects for females. They also show
      non-additive effects of economic inequality for males that moderate both the rise
      and decline of smoking with national income and non-additive effects of gender
      equality for females that moderate the positive effect of national income.

PMID- 21874073
TI  - Socioeconomic Distinction, Cultural Tastes, and Cigarette Smoking.
AB  - OBJECTIVES: The inverse relationship between socioeconomic status (SES) and
      smoking is typically seen in terms of the greater economic and social resources
      of advantaged groups, but it may also relate to cultural resources. This study
      aims to test theories of symbolic distinction by examining relationships between
      smoking and ostensibly unrelated cultural preferences. METHODS: Using the 1993
      General Social Survey, ordinal logistic regression models, and a three-category
      dependent variable (never, former, and current smoker), the analysis estimates
      relationships of musical likes and dislikes with smoking while controlling for
      SES and social strain. RESULTS: Preferences for classical music are associated
      with lower smoking, while preferences for bluegrass, jazz, and heavy metal music
      are associated with higher smoking. CONCLUSIONS: The results suggest that SES
      groups may use smoking, like other cultural tastes, to distinguish their
      lifestyles from those of others.

PMID- 21874074
TI  - The interaction between prosody and meaning in second language speech production.
AB  - Research has shown that English and German native speakers use prosodic cues
      during speech production to convey the intended meaning of an utterance. However,
      little is known about whether American L2 learners of German also use such cues
      during L2 production. The present study shows that intermediate-level L2 learners
      of German (English L1) use prosodic cues to disambiguate syntactically ambiguous
      German sentences during a contextualized sentence production task. These results
      highlight the interaction between prosody and meaning in L2 speech, suggesting
      ways in which prosodic training is important not only for L2 pronunciation, but
      also L2 listening and reading comprehension.

PMID- 21874075
TI  - Species Numbers in Bacteria.
AB  - A modified biological species definition (BSD), i.e., that bacteria exchange
      genes within a species, but not usually between species, is shown to apply to
      bacteria. The formal definition of bacterial species, which is more conservative
      than the modified BSD, is framed in terms of DNA hybridization. From this I
      estimate there are a million species of bacteria in 30 grams of rich forest
      topsoil and propose that there will be at least a billion species worldwide.

PMID- 21874076
TI  - THE MODERATING EFFECTS OF ETHNIC IDENTIFICATION ON THE RELATIONSHIP BETWEEN
      PARENTAL MONITORING AND SUBSTANCE USE IN MEXICAN HERITAGE ADOLESCENTS IN THE
      SOUTHWEST UNITED STATES.
AB  - The purpose of this study was to assess the combined effects of ethnic
      identification and perceived parental monitoring on the substance use of a sample
      of 162 male and 192 female Mexican heritage seventh grade adolescents. Parental
      monitoring predicted lower risk for substance use. An interaction of ethnic
      identification by parental monitoring was observed with parental monitoring
      exhibiting stronger effects in decreasing use of alcohol use among boys who
      scored low on ethnic identification. For girls, decreased substance use was
      predicted by stronger parental monitoring coupled with high ethnic
      identification. Results are discussed in terms of how the youth's ethnic
      identification is a distinct process from acculturation, and how ethnic
      identification may operate as an added protective factor in conjunction with
      parental monitoring, as protective factors against adolescent substance abuse.

PMID- 21874077
TI  - Unveiling phonological universals: A linguist who asks "why" is (inter alia) an
      experimental psychologist.
AB  - Evans and Levinson are right to hold theories of language accountable for
      language diversity, but typological data alone cannot determine the structure of
      mental phonological grammars. Grammatical universals are nonetheless testable by
      formal and experimental methods, and the growing research in experimental
      phonology demonstrates the viability of a comparative experimental evaluation of
      the UG hypothesis.

PMID- 21874078
TI  - Household strategies in the face of resource scarcity in coastal Ghana: are they
      associated with development priorities?
AB  - In many developing regions, women and young girls spend several hours daily in
      the collection of natural resources. Still the link between these household
      resource strategies and stakeholder perceptions of development priorities remains
      unexplored. This project examines this association with survey data
      representative of the adult population from Ghana's Coastal Region. Although
      natural resource scarcity and the sustainability of resource use represent key
      development challenges, there are others (e.g., energy, sanitation, employment,
      and educational opportunities). As such, even in the face of natural resource
      scarcity, individuals may place greater importance on other dimensions of
      development, especially if household resource strategies are perceived as
      relatively efficient. The analytical focus here is on water and the results
      suggest that gender roles shape household water collection strategies, while also
      shaping these strategies' perceived opportunity costs. Specifically, Ghanian
      adults more often see drinking water provision as their primary development need
      when water sources are distant and/or when male household members collect water
      (particularly male heads). In the end, I argue that social science inquiry
      benefits by contextualizing social dynamics within environmental context,
      particularly within cultural settings in which human subsistence is intimately
      tied to the state of the natural environment.

PMID- 21874079
TI  - ASSESSING ENVIRONMENTAL INEQUALITY: HOW THE CONCLUSIONS WE DRAW VARY ACCORDING TO
      THE DEFINITIONS WE EMPLOY.
AB  - This article demonstrates that the conclusions environmental inequality
      researchers draw vary according to the definitions of environmental inequality
      they employ and that researchers can use a single set of results to test for the
      existence of multiple forms of environmental inequality. In order to illustrate
      these points, I set forth five definitions of environmental inequality, list the
      kinds of evidence we must obtain in order to determine whether each form of
      environmental inequality exists, and show how conclusions drawn from several
      recent environmental inequality studies vary depending on the definition of
      environmental inequality we employ. My goal is not to show that any one
      definition is superior to the others; nor am I trying to generalize from the
      studies reported here to a broader set of research findings. Instead, my goal is
      to a) show that we can use a single set of results to address a variety of
      environmental justice concerns and b) demonstrate that our interpretations of
      environmental inequality research have been too narrowly focused on one set of
      environmental inequality outcomes.

PMID- 21874080
TI  - SINGLE MOTHER FAMILIES AND INDUSTRIAL POLLUTION IN METROPOLITAN AMERICA.
AB  - Environmental inequality researchers have studied the distribution of social
      groups around a variety of environmental hazards. However, researchers have
      focused their attention primarily on race and class-based environmental
      inequality, largely ignoring the question of whether other subordinate groups
      children, the elderly, women, welfare recipients, single mother families-are
      disproportionately burdened by environmental hazards. I address this gap in the
      literature by asking whether single mother families are overrepresented in
      environmentally hazardous neighborhoods, whether the percentage of single mother
      families in a neighborhood is a better predictor than a neighborhood's racial and
      income characteristics of environmental hazard presence levels, and whether the
      representation of single mother families in environmentally hazardous
      neighborhoods is similar to that of single father families and married parent
      families.

PMID- 21874081
TI  - Pastoral Herding Strategies and Governmental Management Objectives: Predation
      Compensation as a Risk Buffering Strategy in the Saami Reindeer Husbandry.
AB  - Previously it has been found that an important risk buffering strategy in the
      Saami reindeer husbandry in Norway is the accumulation of large herds of reindeer
      as this increases long-term household viability. Nevertheless, few studies have
      investigated how official policies, such as economic compensation for livestock
      losses, can influence pastoral strategies. This study investigated the effect of
      received predation compensation on individual husbandry units' future herd size.
      The main finding in this study is that predation compensation had a positive
      effect on husbandry units' future herd size. The effect of predation
      compensation, however, was nonlinear in some years, indicating that predation
      compensation had a positive effect on future herd size only up to a certain
      threshold whereby adding additional predation compensation had little effect on
      future herd size. More importantly, the effect of predation compensation was
      positive after controlling for reindeer density, indicating that for a given
      reindeer density husbandry units receiving more predation compensation performed
      better (measured as the size of future herds) compared to husbandry units
      receiving less compensation.

PMID- 21874082
TI  - Age and sex influence marmot antipredator behavior during periods of heightened
      risk.
AB  - Animals adjust their antipredator behavior according to environmental variation
      in risk, and to account for their ability to respond to threats. Intrinsic
      factors that influence an animal's ability to respond to predators (e.g., age,
      body condition) should explain variation in antipredator behavior. For example, a
      juvenile might allocate more time to vigilance than an adult because mortality as
      a result of predation is often high for this age class; however, the relationship
      between age/vulnerability and antipredator behavior is not always clear or as
      predicted. We explored the influence of intrinsic factors on yellow-bellied
      marmot (Marmota flaviventris) antipredator behavior using data pooled from 4
      years of experiments. We hypothesized that inherently vulnerable animals (e.g.,
      young, males, and individuals in poor condition) would exhibit more antipredator
      behavior prior to and immediately following conspecific alarm calls. As expected,
      males and yearlings suppressed foraging more than females and adults following
      alarm call playbacks. In contrast to predictions, animals in better condition
      respond more than animals in below average condition. Interestingly, these
      intrinsic properties did not influence baseline time budgets; animals of all
      ages, sexes, and condition levels devoted comparable amounts of time to foraging
      prior to alarm calls. Our results support the hypothesis that inherent
      differences in vulnerability influence antipredator behavior; furthermore, it
      appears that a crucial, but poorly acknowledged, interaction exists between risk
      and state-dependence. Elevated risk may be required to reveal the workings of
      state-dependent behavior, and studies of antipredator behavior in a single
      context may draw incomplete conclusions about age- or sex-specific strategies.

PMID- 21874083
TI  - The genetic mating system of a sea spider with male-biased sexual size
      dimorphism: evidence for paternity skew despite random mating success.
AB  - Male-biased size dimorphism is usually expected to evolve in taxa with intense
      male-male competition for mates, and it is hence associated with high variances
      in male mating success. Most species of pycnogonid sea spiders exhibit female
      biased size dimorphism, and are notable among arthropods for having exclusive
      male parental care of embryos. Relatively little, however, is known about their
      natural history, breeding ecology, and mating systems. Here we first show that
      Ammothella biunguiculata, a small intertidal sea spider, exhibits male-biased
      size dimorphism. Moreover, we combine genetic parentage analysis with
      quantitative measures of sexual selection to show that male body size does not
      appear to be under directional selection. Simulations of random mating revealed
      that mate acquisition in this species is largely driven by chance factors,
      although actual paternity success is likely non-randomly distributed. Finally,
      the opportunity for sexual selection (I(s)), an indirect metric for the potential
      strength of sexual selection, in A. biunguiculata males was less than half of
      that estimated in a sea spider with female-biased size dimorphism, suggesting the
      direction of size dimorphism may not be a reliable predictor of the intensity of
      sexual selection in this group. We highlight the suitability of pycnogonids as
      model systems for addressing questions relating parental investment and sexual
      selection, as well as the current lack of basic information on their natural
      history and breeding ecology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s00265-011-1170-x) contains supplementary
      material, which is available to authorized users.

PMID- 21874084
TI  - Testing the priority-of-access model in a seasonally breeding primate species.
AB  - In mammals, when females are clumped in space, male access to receptive females
      is usually determined by a dominance hierarchy based on fighting ability. In
      polygynandrous primates, as opposed to most mammalian species, the strength of
      the relationship between male social status and reproductive success varies
      greatly. It has been proposed that the degree to which paternity is determined by
      male rank decreases with increasing female reproductive synchrony. The priority
      of-access model (PoA) predicts male reproductive success based on female
      synchrony and male dominance rank. To date, most tests of the PoA using paternity
      data involved nonseasonally breeding species. Here, we examine whether the PoA
      explains the relatively low reproductive skew in relation to dominance rank
      reported in the rhesus macaque, a strictly seasonal species. We collected
      behavioral, genetic, and hormonal data on one group of the free-ranging
      population on Cayo Santiago (Puerto Rico) for 2 years. The PoA correctly
      predicted the steepness of male reproductive skew, but not its relationship to
      male dominance: the most successful sire, fathering one third of the infants, was
      high but not top ranking. In contrast, mating success was not significantly
      skewed, suggesting that other mechanisms than social status contributed to male
      reproductive success. Dominance may be less important for paternity in rhesus
      macaques than in other primate species because it is reached through queuing
      rather than contest, leading to alpha males not necessarily being the strongest
      or most attractive male. More work is needed to fully elucidate the mechanisms
      determining paternity in rhesus macaques.

PMID- 21874085
TI  - Particle Concentrations and Effectiveness of Free-Standing Air Filters in
      Bedrooms of Children with Asthma in Detroit, Michigan.
AB  - Asthma can be exacerbated by environmental factors including airborne particulate
      matter (PM) and environmental tobacco smoke (ETS). We report on a study designed
      to characterize PM levels and the effectiveness of filters on pollutant exposures
      of children with asthma. 126 households with an asthmatic child in Detroit,
      Michigan, were recruited and randomized into control or treatment groups. Both
      groups received asthma education; the latter also received a free-standing high
      efficiency air filter placed in the child's bedroom. Information regarding the
      home, emission sources, and occupant activities was obtained using surveys
      administered to the child's caregiver and a household inspection. Over a one-week
      period, we measured PM, carbon dioxide (CO(2)), environmental tobacco smoke (ETS)
      tracers, and air exchange rates (AERs). Filters were installed at midweek. Before
      filter installation, PM concentrations averaged 28 ug m(-3), number
      concentrations averaged 70,777 and 1,471 L(-1) in 0.3-1.0 and 1-5 um size ranges,
      respectively, and the median CO(2) concentration was 1,018 ppm. ETS tracers were
      detected in 23 of 38 homes where smoking was unrestricted and occupants included
      smokers and, when detected, PM concentrations were elevated by an average of 15
      ug m(-3). Filter use reduced PM concentrations by an average of 69 to 80%.
      Simulation models representing location conditions show that filter air flow,
      room volume and AERs are the key parameters affecting PM removal, however,
      filters can achieve substantial removal in even "worst" case applications. While
      PM levels in homes with asthmatic children can be high, levels can be
      dramatically reduced using filters.

PMID- 21874086
TI  - Putting the relationship between social anxiety and alcohol use into context: A
      daily diary investigation of drinking in response to embarrassing events.
AB  - The goal of this study was to clarify mixed findings regarding the association
      between dispositional social anxiety and drinking among college students by using
      a daily diary method to examine whether a within-person social-contextual event
      moderated the relationship between social anxiety and alcohol use. College
      students (n = 476) completed a measure of dispositional social anxiety and then
      for 30 days reported whether they experienced an embarrassing event in public and
      the amount of alcohol they drank each day. We examined whether experiencing an
      embarrassing event moderated the relationship between dispositional social
      anxiety and alcohol use for same-day, same-evening, next-day, and next-evening
      drinking. While there was a positive relationship between dispositional social
      anxiety and alcohol use on evenings when an embarrassing event occurred earlier
      that day, this appeared to be driven by a reduction in drinking among those low
      in social anxiety. Individuals with high social anxiety drank in the evening
      regardless of embarrassing event occurrence. Results suggest that people with low
      social anxiety show an adaptive response to embarrassing events by lowering
      drinking on such evenings, while those with high social anxiety may drink to
      reduce their already high levels of anxiety independent of daily social events.

PMID- 21874087
TI  - Model-on-Demand Predictive Control for Nonlinear Hybrid Systems With Application
      to Adaptive Behavioral Interventions.
AB  - This paper presents a data-centric modeling and predictive control approach for
      nonlinear hybrid systems. System identification of hybrid systems represents a
      challenging problem because model parameters depend on the mode or operating
      point of the system. The proposed algorithm applies Model-on-Demand (MoD)
      estimation to generate a local linear approximation of the nonlinear hybrid
      system at each time step, using a small subset of data selected by an adaptive
      bandwidth selector. The appeal of the MoD approach lies in the fact that model
      parameters are estimated based on a current operating point; hence estimation of
      locations or modes governed by autonomous discrete events is achieved
      automatically. The local MoD model is then converted into a mixed logical
      dynamical (MLD) system representation which can be used directly in a model
      predictive control (MPC) law for hybrid systems using multiple-degree-of-freedom
      tuning. The effectiveness of the proposed MoD predictive control algorithm for
      nonlinear hybrid systems is demonstrated on a hypothetical adaptive behavioral
      intervention problem inspired by Fast Track, a real-life preventive intervention
      for improving parental function and reducing conduct disorder in at-risk
      children. Simulation results demonstrate that the proposed algorithm can be
      useful for adaptive intervention problems exhibiting both nonlinear and hybrid
      character.